PMID- 21068493
TI  - EUS-guided choledochoduodenostomy for biliary drainage in unresectable pancreatic
      cancer: a case series.
AB  - CONTEXT: Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure
      of choice for biliary decompression in patients with unresectable pancreatic
      cancer. However, it may be unsuccessful in 3 to 10% of cases. When ERCP is
      unsuccessful, the usual alternatives are percutaneous transhepatic biliary
      drainage or surgery. Recently, several authors have reported the use of EUS
      guided biliary drainage in patients with malignant biliary obstructions, with
      acceptable success and complication rates. We describe three cases of
      unresectable pancreatic cancer associated with obstructive jaundice, treated by
      EUS-guided biliary drainage. CASE REPORT: Three patients with unresectable
      pancreatic cancer, associated with obstructive jaundice, were included. ERCP was
      unsuccessful because of complete tumor obstruction of the distal common bile duct
      and papilla invasion. An EUS-guided rendezvous maneuver was attempted, without
      success. Then, EUS-guided choledochoduodenostomy, with a partially covered self
      expanding metal stent, was performed in the same procedure. There were no early
      complications and the procedure was also clinically effective in relieving
      jaundice in all cases. CONCLUSIONS: EUS-guided biliary drainage is a feasible
      alternative to percutaneous transhepatic biliary drainage or surgery in
      unresectable pancreatic cancer with obstructive jaundice when ERCP fails.
      However, the development of new specific instruments and studies comparing this
      procedure with percutaneous transhepatic biliary drainage and surgery are needed.

PMID- 21068494
TI  - Choledochal cyst with chronic pancreatitis: presentation and management.
AB  - CONTEXT: Choledochal cysts are benign congenital cystic dilatations of the common
      bile duct. They are usually associated with pancreatobiliary malunion resulting
      in long-term complications, such as acute pancreatitis and bile duct cancer.
      However, the occurrence of chronic pancreatitis with a choledochal cyst is rarely
      reported. CASE REPORTS: We report three cases of choledochal cysts associated
      with chronic pancreatitis with their presentation and management. The choledochal
      cysts were classified according to the Alonso-Lej classification with Todani
      modifications, based on radiographic and operative findings. Chronic pancreatitis
      was defined using Marseille criteria (1984). Two patients had a type I
      choledochal cyst and one had a type IV-A. All cases had chronic calcific
      pancreatitis with a grossly dilated main pancreatic duct. Abdominal pain was the
      most common presentation, present in all three patients while jaundice was seen
      in one patient. The laboratory parameters and MRI/MRCP helped to confirm the
      diagnosis. All patients underwent cyst excision with drainage and had an
      uneventful postoperative course. At a median follow-up of 9 months, two patients
      were asymptomatic and one patient, who developed duodenal obstruction, underwent
      gastrojejunostomy. CONCLUSIONS: the association of a choledochal cyst with
      chronic pancreatitis may be etiologically related. Excision of the cyst with
      lateral pancreaticojejunostomy can be performed safely and is usually curative.

PMID- 21068495
TI  - Isolated supraclavicular lymph node metastasis in pancreatic adenocarcinoma: a
      report of three cases and review of the literature.
AB  - CONTEXT: Supraclavicular lymph nodes represent a rare site of metastasis in
      pancreatic cancer. We report three cases of pancreatic adenocarcinoma with
      metastases to supraclavicular lymph nodes. CASE REPORT: A 51-year-old male was
      diagnosed with locally advanced pancreatic adenocarcinoma on computed tomography
      (CT) scan. He was recommended neoadjuvant chemotherapy followed by chemoradiation
      therapy. However, positron emission tomography (PET)/CT scans and subsequent fine
      needle aspiration cytology showed supraclavicular lymph node metastasis. The
      patient received systemic chemotherapy for metastatic pancreatic adenocarcinoma.
      The second patient, a 66-year-old female with pancreatic adenocarcinoma,
      underwent pancreaticoduodenectomy and was found to have peripancreatic lymph node
      involvement. She received adjuvant chemotherapy and was followed-up with
      surveillance CT scans, which did not reveal any metastasis. However, the patient
      complained of neck swelling. PET/CT scan and biopsy revealed supraclavicular
      lymph node metastasis from a pancreatic adenocarcinoma primary. The third
      patient, a 79-year-old male with a past history of thyroid carcinoma who was
      treated with partial thyroidectomy, developed neck swelling 4 years after his
      surgery. Fine needle aspiration cytology was consistent with known papillary
      thyroid carcinoma. Staging evaluations revealed a pancreatic mass for which he
      underwent subtotal pancreatectomy and splenectomy. Histopathology revealed grade
      3 pancreatic adenocarcinoma. Excisional biopsy of a supraclavicular lymph node
      showed metastatic pancreatic adenocarcinoma. PET/CT results were consistent with
      these findings. CONCLUSION: In patients with pancreatic adenocarcinoma,
      supraclavicular lymph node metastasis represents an uncommon, but clinically
      significant finding that can lead to changes in treatment planning. PET imaging
      represents a valuable tool in the detection and follow up of these patients.

PMID- 21068496
TI  - Gastric involvement in autoimmune pancreatitis: MDCT and histopathologic
      features.
AB  - CONTEXT: Autoimmune pancreatitis is a relatively rare, yet well described cause
      of chronic pancreatitis. Extrapancreatic findings are now recognized as important
      manifestations of this entity and viewed as part of a larger disease process
      tentatively named "IgG4-associated sclerotic disease". CASE REPORT: We herein
      report a case of autoimmune pancreatitis with histopathologically proven gastric
      involvement. We also describe and illustrate the multidetector-row computed
      tomography appearance of gastric involvement in IgG4-associated sclerotic
      disease. CONCLUSION: Autoimmune pancreatitis is increasingly recognized as a
      multi-systemic disease whose early recognition dramatically affects patient
      management. Knowledge of the computed tomography appearance of gastric
      involvement in autoimmune pancreatitis can aid in diagnosis.

PMID- 21068497
TI  - Acute pancreatitis following doxycycline and ornidazole coadministration.
AB  - CONTEXT: Drugs are related to the etiology of acute pancreatitis in approximately
      1.4-2.0% of cases. Although antibiotics constitute a small number of the drugs
      suspected, tetracycline is the most encountered antibiotic among those drugs.
      CASE REPORT: A 33-year-old woman was admitted to the emergency room complaining
      of nausea and abdominal pain after the use of doxycycline 500 mg and ornidazole
      500 mg twice daily for three days for a vaginal infection. She experienced
      epigastric pain, which worsened over time and radiated to her back. After a
      detailed evaluation, she was diagnosed as having mild acute pancreatitis which
      improved with medical treatment. All other possible causes of pancreatitis were
      eliminated. CONCLUSIONS: Antibiotic-associated pancreatitis usually has a silent
      and mild course. To the best of our knowledge the literature reports only two
      cases of doxycycline-induced acute pancreatitis reported and there are no reports
      of pancreatitis associated with ornidazole. Our case is the first case reported
      in which doxycycline and ornidazole coadministration induced acute pancreatitis.

PMID- 21068498
TI  - Cystic lymphangioma of the pancreas: diagnostic and therapeutic challenges.
AB  - CONTEXT: Cystic lymphangiomas originate as benign masses which occur mostly in
      children especially in the head and neck region and/or the groin. Although
      abdominal lymphangiomas are rare, they are most commonly reported in adults. In
      addition, pancreatic involvement is rare. Lymphatic malformation with blockage of
      the lymphatic flow is the most common etiology leading to the formation of
      lymphangiomas. Cystic lymphangiomas should always be included in the differential
      diagnosis of abdominal masses which present with mass effect signs and symptoms.
      Due to its rarity, it forms a diagnostic and therapeutic challenge for the
      clinician. CASE REPORT: We herein report the case of a 43-year-old man with a
      cystic lymphangioma detected in the head of the pancreas and describe the
      surgical procedure utilized as the therapeutic medium. CONCLUSION: To remove this
      mass, we utilized a modified approach to a classic pancreaticoduodenectomy. This
      technique involved resection of the head of the pancreas while preserving the
      upper 2nd portion of the duodenum and the ampulla of Vater. The result of our 30
      month follow-up of this patient has been very satisfactory with no complications.

PMID- 21068499
TI  - Idiopathic hyperammonemia in a patient with total pancreatectomy and islet cell
      transplantation.
AB  - CONTEXT: Idiopathic hyperammonemia is characterized by elevated serum ammonia
      associated with neurological deterioration of no other obvious etiology
      associated with relatively normal liver function tests and normal amino-acid
      levels. CASE REPORT: We report a case of a 32-year-old woman who presented with
      acute mental status changes with a pelvic abscess approximately a year following
      her total pancreatectomy and islet cell transplant surgery. Her ammonia level was
      elevated to 425 ug/dL. Traditional ammonia-reducing therapies were initiated, but
      proved ineffective. Metabolic, pharmacologic, microbial, and autoimmune causes
      for hyperammonemia were excluded. The patient ultimately required continuous veno
      venous hemofiltration to decrease her ammonia. Ammonia levels decreased following
      continuous veno-venous hemofiltration and the patient's mental status gradually
      returned to baseline. CONCLUSION: Idiopathic hyperammonemia in the setting of
      total pancreatectomy and islet cell transplantation has not been reported before.
      We propose that malnutrition following total pancreatectomy resulting in
      repressed urea cycle enzyme synthesis may have predisposed for this
      hyperammonemia.

PMID- 21068501
TI  - Spontaneous resolution of pulmonary nodules in autoimmune pancreatitis.
AB  - CONTEXT: Autoimmune pancreatitis is a rare benign disorder that can be confused
      with pancreatic cancer and the treatment pathway differs dramatically. CASE
      REPORT: We present a unique case of pulmonary nodules associated with autoimmune
      pancreatitis, that was initially confused for pancreatic cancer which resolved
      spontaneously. Herein we describe the case and subsequent management and discuss
      the ever increasing incidence of autoimmune pancreatitis. CONCLUSION: Pulmonary
      nodules associated with equivocal CT findings of primary pancreatic cancer should
      be treated with suspicion that the primary diagnosis may be incorrect and other
      differential diagnoses should be explored.

PMID- 21068500
TI  - Hemosuccus pancreaticus associated with segmental arterial mediolysis
      successfully treated by transarterial embolization.
AB  - CONTEXT: Hemosuccus pancreaticus, a rare cause of intermittent upper
      gastrointestinal bleeding, is usually caused by the rupture of an aneurysm
      associated with chronic pancreatitis. Segmental arterial mediolysis is a rare non
      arteriosclerotic, non-inflammatory vascular disease characterized by
      vacuolization and lysis of the arterial smooth muscle cells. Segmental arterial
      mediolysis often causes intra-abdominal hemorrhage through aneurysm rupture. To
      our knowledge, hemosuccus pancreaticus associated with segmental arterial
      mediolysis has not previously been reported. CASE REPORT: A 59-year-old man had
      suffered from recurrent episodes of epigastric pain and melena. Laboratory data
      showed mild anemia and an elevated serum amylase level. Upper gastrointestinal
      endoscopy revealed bloody pancreatic juice exuding from the papilla of Vater.
      There were no findings suggestive of chronic pancreatitis, such as pancreatic
      calcification, irregularity of the pancreatic duct and atrophy of the pancreas.
      Contrast-enhanced computed tomography revealed a large fusiform aneurysm of the
      middle-distal splenic artery, and dissection of the proximal splenic artery and
      celiac artery. Leakage of contrast medium from the aneurysm into the main
      pancreatic duct was also evident. Angiography clearly revealed a fusiform
      aneurysm of the splenic artery. This was managed successfully by transarterial
      coil embolization and the patient has subsequently shown no recurrence of
      epigastric pain or melena. CONCLUSION: Segmental arterial mediolysis is a very
      rare cause of hemosuccus pancreaticus not associated with chronic pancreatitis.
      Transcatheter arterial embolization is useful for treatment of ruptured aneurysm
      associated with segmental arterial mediolysis.

PMID- 21068502
TI  - Middle-preserving pancreatectomy for multifocal metastatic renal cell carcinoma
      located in the head, body and tail of the pancreas. A case report.
AB  - CONTEXT: Postoperative endocrine and exocrine insufficiencies following
      traditional pancreatectomies might cause a deterioration of the quality of life
      and surgical outcome. Parenchyma-sparing pancreatectomies have been utilized in
      benign lesions and low-grade malignancies. CASE REPORT: A 67-year-old female with
      a past history of right nephrectomy for renal cell carcinoma 20 years earlier was
      referred to our institute with obstructive jaundice and multiple nodules in the
      pancreas. Computed tomography demonstrated five well-demarcated, strongly
      enhanced nodules with diameters of 5.5 cm in the head, 2.0 and 1.8 cm in the
      body, and 1.2 and 1.0 cm in the tail. Fluorine-18 fluorodeoxyglucose positron
      emission tomography did not demonstrate any extrapancreatic uptake. A middle
      preserving pancreatectomy was performed after ultrasonography had confirmed
      arterial perfusion in the middle segment. A histological study demonstrated
      metastatic clear cell renal carcinoma. To date, the patient has remained without
      recurrence for two and a half years since surgery. A minimal administration of
      insulin has been necessary; however, C-peptide is detectable and nutritional
      status is comparatively good. CONCLUSION: A middle-preserving pancreatectomy is a
      useful procedure in a parenchyma-sparing pancreatectomy for resecting multifocal
      lesions in the head, body and tail of the pancreas.

PMID- 21068503
TI  - Total pancreaticoduodenectomy and segmental resection of superior mesenteric vein
      portal vein confluence with autologous splenic vein graft in mucinous
      cystadenocarcinoma of the pancreas.
AB  - CONTEXT: Mucinous cystic tumors occur almost exclusively in middle-aged women and
      in the body or tail of the pancreas. Mucinous cystadenocarcinoma, a malignant sub
      type of mucinous cystic tumors, in the head of the pancreas and in a middle-aged
      man is extraordinary, and the prognosis and proper management of mucinous
      cystadenocarcinoma has not been well documented. CASE REPORT: A 52-year-old male
      patient with a mucinous cystadenocarcinoma approximately 5.5 cm in size in the
      head of the pancreas underwent a total pancreaticoduodenectomy and segmental
      resection of the superior mesenteric vein-portal vein confluence with an
      autologous splenic vein graft due to tumor invasion. His postoperative course was
      uneventful and he received adjuvant chemotherapy. He has been followed-up
      periodically for more than 30 months after surgery without evidence of
      recurrence. CONCLUSION: Mucinous cystadenocarcinoma in the head of the pancreas
      in a middle-aged man is an extremely rare case. Because mucinous
      cystadenocarcinomas have a relatively good prognosis, an aggressive approach with
      major vascular resection is warranted in well-selected patients. Splenic vein
      interposition grafting could be used in cases which undergo total
      pancreaticoduodenectomy with segmental resection of the superior mesenteric vein
      portal vein confluence if the splenic vein is healthy.

PMID- 21068504
TI  - Pancreaticojejunostomy: images of an invagination technique.

PMID- 21068505
TI  - Pancreatic metastasis from colon carcinoma treated with radiotherapy with
      palliative benefit.

PMID- 21068506
TI  - Some more comments on 'folate deficiency in chronic pancreatitis'.

PMID- 21068507
TI  - Management of pain in chronic pancreatitis with home elemental diet ingestion.

PMID- 21068511
TI  - Pancreatic cancer and cancer screening programs: from nihilism to hope.

PMID- 21068512
TI  - Three-dimensional quantitative volumetry of chronic total occlusion plaque using
      coronary multidetector computed tomography.
AB  - BACKGROUND: The purpose of the present study was to investigate whether
      multidetector computed tomography (MDCT) can identify the nature of chronic total
      occlusion (CTO) plaque, which cannot be measured quantitatively using traditional
      coronary angiography, and predict the success of percutaneous coronary
      intervention (PCI). METHODS AND RESULTS: MDCT and 3-dimensional volumetric
      radiologic density analysis was performed for 186 consecutive CTO lesions. Plaque
      characteristics were determined using Hounsfield units (HU) of the image voxels.
      The remodeling index decreased significantly as the duration of CTO lengthened.
      Volumetric plaque analysis using HU showed that volumetric fraction of
      calcification (>324HU) did not, but low-density plaque (<49HU) did decrease
      significantly as the duration of CTO lengthened. The overall PCI success rate was
      77.4% (144/186). In addition to the unknown or >12-month occlusion duration (odds
      ratio [OR]=3.0, 95% confidence interval [CI]=1.4-6.5, P=0.005), 2 MDCT
      parameters, that is, lesion length >18mm (OR=2.7, 95%CI=1.1-6.4, P=0.024) and
      segmental radiologic density >139HU (OR=2.7, 95%CI=1.2-6.4, P=0.021), were
      independent predictors of PCI failure on multivariate analysis. CONCLUSIONS: MDCT
      might be helpful for the prediction of successful CTO PCI. In addition to the
      occlusion duration, lesion length and high segmental radiologic density measured
      on MDCT were significant predictors of PCI failure in the present study.

PMID- 21068515
TI  - Acute myeloid leukemia with mastocytic and megakaryocytic differentiation in a
      calf.
AB  - A diagnosis of acute myeloid leukemia was made in a 10-month-old Holstein female
      calf. The leukemia was macroscopically characterized by great enlargement of the
      spleen and moderate enlargement of some lymph nodes. Histochemical and
      immunohistochemical examination disclosed the presence of neoplastic cells either
      containing metachromatic and tryptase-positive granules or expressing factor VIII
      related antigen. The granules, which were positive for naphthol AS-D
      chloroacetate esterase and did not have particulate contents, were distinct from
      those of basophilic leukemia cells. This leukemia was thought to be derived from
      a common myeloid progenitor capable of giving rise to megakaryocyte-erythrocyte
      progenitors and granulocyte-monocyte progenitors with the ability to
      differentiate into mast cells.

PMID- 21068513
TI  - Transition of thyroid autoantibodies by rituximab treatment for thyroid MALT
      lymphoma.
AB  - Thyroid MALT lymphoma is an extremely rare malignancy believed to arise against a
      background of Hashimoto's thyroiditis. Rituximab is a monoclonal antibody
      directed against B cell specific antigen CD20. Recently, there have been reports
      that rituximab is effective for autoimmune thyroid diseases such as Graves'
      disease as well as for treatment of B cell malignant lymphoma. We present the
      changes in thyroid autoantibodies in Hashimoto's thyroiditis after rituximab
      administration for 3 cases of thyroid MALT lymphoma. Case 1 had been taking
      levothyroxine and was diagnosed with thyroid MALT lymphoma. She was treated with
      rituximab monotherapy, and her thyroid enlargement improved. Anti-thyroid
      peroxidase antibody (TPOAb) turned negative after rituximab monotherapy, and TSH
      levels decreased with the same levothyroxine dosage. Case 2 was diagnosed with
      recurrent thyroid MALT lymphoma after chemotherapy (CHOP). He suffered from leg
      sensory disturbance because of vincristine sulfate. The patient was treated with
      rituximab. TPOAb decreased, but did not turn negative. TSH levels were within
      normal range during the disease course, but TSH levels were low in comparison
      with before rituximab therapy. Case 3 was diagnosed with thyroid MALT lymphoma
      after radiation therapy on the neck for laryngeal cancer. Thyroid enlargement
      improved after rituximab monotherapy, and thyroid autoantibody levels decreased.
      TSH increased transiently after radiation therapy, but TSH decreased gradually
      without levothyroxine after rituximab monotherapy. We report 3 cases in which
      thyroid autoantibody levels in Hashimoto's thyroiditis decreased after rituximab
      monotherapy for thyroid MALT lymphoma, but it is controversial whether thyroid
      dysfunction due to Hashimoto's thyroiditis is restored.

PMID- 21068516
TI  - Localization of eNOS in the olfactory epithelium of the rat.
AB  - Nitric oxide (NO) is a free radical and produced from L-arginine by nitric oxide
      synthase (NOS). Since NO is recently suggested to be involved in olfactory
      perception, the expression of eNOS, an isoform of NOS, was examined in the rat
      olfactory epithelium. The activity of NADPH-diaphorase was also examined as a
      marker of NOS. In the dorsomedial region of the nasal cavity, intensely positive
      reactions for NADPH-diaphorase were observed in the entire cytoplasm of sensory
      cells (olfactory cells). By immunohistochemistry, intensely positive reactions
      for eNOS were also found in the dorsomedial region of the nasal cavity. These
      reactions were observed on the free border of the olfactory epithelium. By
      immunoelectron microscopy, positive reactions for eNOS were found in the cilia of
      olfactory cells. In addition, in situ hybridization analysis of the olfactory
      epithelium revealed the expression of eNOS mRNA in the olfactory cells. These
      results indicate the presence of eNOS in the olfactory cells of the rat, and
      differential expression of eNOS in the olfactory epithelium depending on the
      regions of the nasal cavity. In addition, NO produced by eNOS may be involved in
      olfactory perception in the cilia of olfactory cells.

PMID- 21068517
TI  - Pharmacokinetics of a florfenicol-tylosin combination after intravenous and
      intramuscular administration to beagle dogs.
AB  - A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination
      product was conducted in six beagle dogs after intravenous (IV) and intramuscular
      (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin).
      Serum drug concentrations were determined by a validated high performance liquid
      chromatography (HPLC) using UV detection. A rapid and nearly complete absorption
      of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6%
      (tylosin), prolonged elimination half-life, and high tissue penetration with
      steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg
      (tylosin) were observed. Additional studies, including pharmacodynamic and
      toxicological evaluation are required before recommendations can be made
      regarding the clinical application of the product in dogs.

PMID- 21068518
TI  - Unilateral facial paresis secondary to a suspected brainstem arachnoid cyst in a
      Maltese dog.
AB  - An 8-year-old, intact female Maltese dog was presented with decreased tear
      production and unilateral loss of eye blinking. Neuro-ophthalmic examination and
      brain magnetic resonance imaging were performed to determine the origin of facial
      paresis. A cystic lesion in the left pontomedullary region which displayed equal
      intensity to cerebrospinal fluid was revealed. Hyposignality was noted on fluid
      attenuated inversion recovery sequences, and the lesion was suggestive of an
      arachnoid cyst. This report described unilateral facial nerve dysfunction that
      resulted from a suspected brainstem arachnoid cyst in an unusual anatomic
      location.

PMID- 21068519
TI  - Hypertension promotes phosphorylation of focal adhesion kinase and proline-rich
      tyrosine kinase 2 in rats: implication for the pathogenesis of hypertensive
      vascular disease.
AB  - Atherosclerosis is initiated by adhesion and infiltration of inflammatory
      leukocytes into the intima, where non-receptor protein tyrosine kinases, such as
      focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), play
      important roles as intracellular messengers of mechanical and biochemical
      signals. In the present study, we examined whether FAK and PYK2 are up-regulated
      by elevated blood pressure or circulating humoral factors in hypertension. We
      used a rat model of abdominal aortic banding that allows separate evaluation of
      elevated blood pressure (upper body) and circulating humoral factors (lower
      body). We obtained the proximal and distal aortas of the banding site, 6 hours, 3
      days, and 1 and 4 weeks after the banding procedure, for evaluation of
      phosphorylation of FAK and PYK2 by Western blotting. Arterial pressure was
      significantly elevated only in the upper body throughout the experimental period.
      The expression of FAK and the FAK phosphorylation were significantly increased at
      1 and 4 weeks only in the proximal aorta. This was also the case for the
      expression of total PYK2 and the PYK2 phosphorylation. In contrast, there was no
      significant change in FAK or PYK2 phosphorylation in the distal aorta, whereas
      plasma levels of angiotensin II were systemically elevated. In sham-operated
      rats, no change in FAK or PYK2 phoshorylation was noted in the proximal and
      distal aortas. These results indicate that phosphorylation of FAK and PYK2 is
      upregulated by elevated blood pressure but not by humoral factors in the rat
      aorta, demonstrating novel aspects of atherogenesis in hypertension.

PMID- 21068520
TI  - Is mean platelet volume increased in behcet's disease with thrombosis?

PMID- 21068522
TI  - Prevalence of stroke/transient ischemic attack among patients with acute coronary
      syndromes in a real-world setting.
AB  - BACKGROUND: Atherothrombosis is a systemic disease that may manifest as acute
      ischemic events in multiple vascular beds. Patients who have experienced an
      atherothrombosis-related ischemic event in 1 vascular bed are at risk for
      developing ischemic events in other vascular beds. Antiplatelet therapy demands
      an understanding of the balance between arterial thrombosis benefit and adverse
      event risk. Clinical trials indicate that dual antiplatelet therapy with aspirin
      and the newer thienopyridines increases the risk of bleeding in patients with
      acute coronary syndromes (ACS) with prior cerebrovascular events. Informed
      clinical decision making requires a better understanding of the real-world
      prevalence of cerebrovascular events. OBJECTIVE AND PURPOSE: To estimate the
      prevalence of stroke and/or transient ischemic attack (TIA) among patients with
      ACS within US health plan populations. METHODS: A retrospective, observational
      cohort study was conducted of patients with ACS in 5 health care claims
      databases. The index event was defined as the first documented inpatient health
      care claim for myocardial infarction or unstable angina. Patients with >=12
      months of pre-index medical care encounter information were included. Stroke/TIA
      was identified by the first health care claim for these conditions any time prior
      to or within 90 days following the index ACS event. RESULTS: Across all
      databases, between 3.8% and 15.7% of patients with ACS had prior stroke/TIA and
      between 3.4% and 11.7% of patients with ACS with no history of cerebrovascular
      events had documented stroke/TIA following the index ACS hospitalization.
      CONCLUSION: Despite important differences between the various database
      populations, there is a high prevalence of documented stroke/TIA in patients with
      ACS both prior to and following the ACS event. These real-world findings, set
      within the context of the increased bleeding risk observed with the newer
      thienopyridines, are important considerations when selecting antiplatelet therapy
      for patients with ACS.

PMID- 21068523
TI  - Choosing the right heparin prophylaxis strategy in medical patients at risk for
      developing VTE: an evidence-based approach.
AB  - Many acutely ill medical patients are at significant risk for developing venous
      thromboembolism (VTE) during hospitalization. Venous thromboembolism risk arises
      from both the presenting clinical condition as well as predisposing risk factors,
      such as advanced age. Thromboprophylaxis is underprescribed in these patients.
      Thrombotic risk assessment could encourage the prescribing of thromboprophylaxis
      and, therefore, improve patient protection against VTE. Current guidelines from
      the American College of Chest Physicians and the International Union of Angiology
      (IUA) recommend thromboprophylaxis with low-dose unfractionated heparin (UFH), a
      low-molecular-weight heparin (LMWH), or fondaparinux for acutely ill medical
      patients with VTE risk factors. However, the optimal dose regimen for UFH is
      unclear. The 2006 evidence-based guidelines from the IUA recommend a 3-times
      daily dose regimen for UFH. However, UFH is usually administered twice daily
      despite a lack of evidence for the superiority of this regimen. Both heparin
      induced thrombocytopenia and bleeding are associated with UFH, and to a lesser
      degree with alternative anticoagulants, such as the LMWHs. If utilized, an
      appropriate prophylaxis regimen in medical patients can reduce the risk of VTE
      and its burden.

PMID- 21068524
TI  - Emerging oral antiplatelet therapies for acute coronary syndromes.
AB  - Emergency department physicians, along with hospitalists and interventional
      cardiologists, provide first-line care for patients experiencing symptoms
      potentially associated with acute coronary syndromes (ACS). Because these health
      care providers encounter and manage patients with varying degrees of risk, a
      clear understanding of the modes of action, benefits, and limitations of various
      therapeutic options is crucial for achieving optimal outcomes in the acute-care
      setting. Oral antiplatelet therapy has a major role in the acute care of patients
      with suspected ACS due to the critical role of platelets in the pathophysiology
      of disease. The current standard-of-care oral antiplatelet therapy for ACS is
      aspirin in combination with a P2Y12 adenosine diphosphate (ADP) receptor
      antagonist, most commonly clopidogrel. Aspirin and P2Y12 antagonists have both
      demonstrated efficacy in reducing morbidity and mortality in patients with ACS,
      but are also associated with increased bleeding risk compared with controls.
      Additionally, despite dual oral antiplatelet therapy, patients remain at
      substantial residual risk for ischemic events due to thrombotic episodes driven
      by platelet activation pathways that are not inhibited by these agents, including
      the protease-activated receptor (PAR)-1 platelet activation pathway, stimulated
      by thrombin. Novel oral antiplatelet agents in advanced clinical development
      include a direct and more readily reversible P2Y12 antagonist, ticagrelor, as
      well as a new class of PAR-1 antagonists, which includes vorapaxar and atopaxar.
      Ticagrelor has shown a significant ischemic benefit and an increase in non
      surgical bleeding over clopidogrel in the large phase 3 Platelet Inhibition and
      Patient Outcomes trial. Results of phase 2 trials with PAR-1 antagonists suggest
      that these agents may provide incremental reduction in ischemic events without a
      bleeding liability. This hypothesis is being evaluated in 2 large ongoing phase 3
      trials with vorapaxar, including the Thrombin Receptor Antagonist for Clinical
      Event Reduction in Acute Coronary Syndrome (TRA*CER) trial in patients with non
      ST-segment elevation ACS.

PMID- 21068525
TI  - Clinical impact of enhanced inhibition of P2Y12-mediated platelet aggregation in
      patients with ST-segment elevation myocardial infarction undergoing percutaneous
      coronary intervention.
AB  - The combination of aspirin and clopidogrel at a loading dose of 300 mg followed
      by a maintenance dose of 75 mg daily is a well-established antiplatelet therapy
      for the secondary prevention of thrombotic complications in the settings of acute
      coronary syndrome and/or percutaneous coronary intervention (PCI). Despite the
      demonstrated clinical benefits associated with this antiplatelet therapy, there
      is accumulating evidence that a consistent proportion of patients persist in
      having high levels of platelet aggregation following standard clopidogrel dose.
      Importantly, the high platelet reactivity after clopidogrel treatment has been
      associated with higher risk for cardiovascular ischemic events, including stent
      thrombosis. This has warranted the need for alternative oral antiplatelet
      regimens that achieve a higher degree of platelet inhibition. Several functional
      studies have shown that a higher clopidogrel loading dose (600 mg) compared with
      standard dose, and novel oral adenosine diphosphate platelet receptor (P2Y12)
      antagonists compared with clopidogrel achieve a faster onset of action, increased
      platelet inhibition, and a more predictable drug response. These more favorable
      pharmacodynamic characteristics are of particular interest in the setting of
      primary PCI for ST-segment elevation myocardial infarction (STEMI), in which
      rapid and consistent inhibition of platelet activation and aggregation is
      desirable for therapeutic success. The present article reviews data on the
      clinical impact of enhanced P2Y12 inhibition with either higher clopidogrel
      dosing or new oral antiplatelet agents, including prasugrel and ticagrelor, in
      the setting of STEMI, focusing on results in the setting of primary PCI.

PMID- 21068526
TI  - History and current trends in sudden cardiac arrest and resuscitation in adults.
AB  - Cardiac arrest occurs when organized cardiac contractility ceases and circulation
      stops. During cardiac arrest, electrical activity may be abnormal or absent, and
      the rhythm documented can be ventricular fibrillation, pulseless ventricular
      tachycardia, pulseless electrical activity, or asystole. It has been estimated
      that 300 000 sudden cardiac arrests occur each year in the United States, with
      75% (225,000) occurring out-of-hospital and 25% (75,000) occurring in-hospital. A
      similar number occur in Europe each year. The 3-phase model of cardiac arrest,
      which proposes that a cardiac arrest progresses through distinct phases as time
      elapses, helps inform research and clinical care by providing a framework for
      improving outcomes from cardiac arrest. Early in an arrest, during the electrical
      phase, defibrillation is paramount. The circulatory phase begins after 4 to 5
      minutes, and interventions to optimize circulation become of primary importance.
      When an arrest is prolonged, lasting for >=10 minutes, the patient passes into
      the metabolic phase, in which significant metabolic derangements have accrued and
      start to dominate arrest physiology. If return of spontaneous circulation occurs
      during this phase, significant injury to diverse organs may have occurred,
      producing a critical illness known as post-cardiac arrest syndrome. The post
      cardiac arrest syndrome has been recognized as a unique entity requiring unique
      therapies for successful management. Recent advances in cardiac arrest care
      include cardiocerebral resuscitation and the use of therapeutic hypothermia to
      treat comatose survivors of cardiac arrest.

PMID- 21068527
TI  - Improving patient outcomes from acute cardiovascular events through regionalized
      systems of care.
AB  - ST-segment elevation myocardial infarction (STEMI), cardiac arrest, and ischemic
      stroke are a diverse group of cardiovascular illnesses linked by the necessity
      for timely intervention in order to maximize patient outcomes. Despite the known
      efficacies of therapies, such as emergent percutaneous coronary intervention
      (PCI), rapid administration of tissue plasminogen activator, and induction of
      therapeutic hypothermia after cardiac arrest, translating these discoveries into
      standard practice nationwide has proven difficult to achieve. Significant
      regional variations in practice are commonplace, and facilities with higher
      patient volumes of STEMI, cardiac arrest, and ischemic stroke consistently have
      better outcomes compared with lower-volume facilities. Such disparities in
      emergency care led the Institute of Medicine in 2006 to describe the existing
      emergency care system as "at the breaking point," and to call for "coordinated,
      regionalized, and accountable" systems of care. An effective and equitable
      regionalized emergency care system would resemble the existing US trauma system
      in some respects, with transparent and standard triage guidelines, cooperation
      between local and regional emergency medical service systems, and an integrated
      network of referring and receiving facilities. Emerging technologies, such as
      telemedicine, will likely play a significant role. Regionalized referral systems,
      such as designated PCI centers and designated stroke centers, are in existence,
      but have largely been reactive and local, and no mechanism is in place to ensure
      equitable distribution of such facilities across all geographic regions. As
      scientific advances in the treatment of these conditions continue to evolve, so
      too must the system of care that provides these therapies. Evidence suggests that
      regionalized systems of care for acute cardiovascular events may increase
      compliance with existing life-saving guidelines and improve patient outcomes.

PMID- 21068528
TI  - A review and meta-analysis of studies on the effect and timing of beta-blocker
      administration in patients with ST-segment elevation myocardial infarction.
AB  - The utility of beta-blockers during an evolving ST-segment elevation myocardial
      infarction (STEMI) has substantial theoretic physiological backing. This coupled
      with early successes using beta-blockers in STEMI promulgated multiple guidelines
      expanding the use of this class of medication to all patients with acute coronary
      syndromes. However, recent studies have questioned the utility of beta-blockers
      in the emergency department in these patients. The purpose of this article is to
      review the evidence behind the use of beta-blockers in the emergency department
      for STEMI patients.

PMID- 21068529
TI  - A case of cyanide poisoning and the use of arterial blood gas analysis to direct
      therapy.
AB  - Cyanide poisoning is a difficult diagnosis for health care professionals.
      Existing reports clearly demonstrate that the initial diagnosis is often missed
      in surreptitious cases. The signs and symptoms can mimic numerous other disease
      processes. We report a case in which a suicidal patient ingested cyanide and was
      found unresponsive by 2 laboratory coworkers. The coworkers employed
      cardiopulmonary resuscitation with mouth-to-mouth resuscitation. The suicidal
      patient died shortly after arrival to the hospital, while the 2 coworkers who
      performed mouth-to-mouth resuscitation presented with signs and symptoms that
      mimicked early cyanide toxicity but were instead due to acute stress response. An
      arterial blood gas analysis may help aid in the diagnosis of cyanide toxicity.
      Electrocardiographic findings in a patient with cyanide poisoning range
      significantly, depending on the stage of the poisoning.

PMID- 21068530
TI  - Cardiac magnetic resonance imaging as a prognostic tool in patients with
      nonischemic cardiomyopathy.
AB  - Technical advancements have enabled cardiac magnetic resonance (CMR) imaging to
      provide a noninvasive assessment of cardiomyopathy. Cardiac magnetic resonance
      imaging acts as the reference standard for quantifying left and right ventricular
      function. It also assesses the etiology of cardiomyopathy by demonstrating the
      presence and size of myocardial scar and by detecting myocardial inflammation and
      interstitial infiltration. Cardiomyopathy can result in early mortality and
      arrhythmic risk, and CMR imaging aids in risk stratification among this group of
      patients. Left ventricular ejection fraction predicts which patients will benefit
      most from implantable cardioverter-defibrillators (ICDs), but this is not a
      perfect marker of arrhythmic risk. The etiology of cardiomyopathy, as assessed
      with CMR imaging, adds further prognostic information with infiltrative
      cardiomyopathies, resulting in higher mortality than idiopathic cardiomyopathies.
      Among patients with nonischemic cardiomyopathy (NICM), the degree of fibrosis as
      determined by the CMR imaging sequence of late gadolinium enhancement (LGE)
      imaging offers further prognostic information. Late gadolinium enhancement
      imaging in patients with NICM portends an approximately 3- to 8-fold greater risk
      of death or hospitalization than NICM without LGE imaging. Further research is
      needed to determine if the presence of LGE will be helpful in predicting which
      patients may benefit from ICD implantation.

PMID- 21068531
TI  - Neurologic complications of cardiac surgery and interventional cardiac
      procedures.
AB  - Neurologic complications of cardiac surgery and interventional cardiac procedures
      may affect the central nervous system or the peripheral nervous system. The most
      common central nervous system complications are strokes and seizures. This
      article provides a succinct neuroanatomic and pathophysiologic approach to a wide
      array of neurologic complications associated with cardiac procedures.

PMID- 21068532
TI  - Resistant hypertension in office practice: a clinical approach.
AB  - Resistant hypertension is defined as blood pressure uncontrolled to guideline
      levels despite the use of >=3 antihypertensive medications. When evaluating
      patients with resistant hypertension, it is important to consider issues such as
      blood pressure measurement technique, lifestyle, other comorbid conditions and
      medications, and the white coat effect. To this point, potential contributing
      factors include obstructive sleep apnea, excess alcohol intake, and use of blood
      pressure-elevating medications, such as nonsteroidal anti-inflammatory drugs,
      sympathomimetics, certain anorexic agents, and oral contraceptives. Secondary
      causes of hypertension are common in patients with resistant hypertension and
      appropriate screening tests should be performed as suggested by signs, symptoms,
      and laboratory abnormalities. In this regard, there is increasing evidence that
      hyperaldosteronism is common in the resistant hypertensive patient group.
      Pharmacologic therapy in patients with resistant hypertension is centered on drug
      combinations that have different mechanisms of action, including diuretics, which
      are essential in maximizing antihypertensive effects. The role of
      mineralocorticoid receptor antagonists is expanding, especially in patients with
      the metabolic syndrome, where aldosterone excess is increasingly recognized as an
      etiology of resistant hypertension. Finally, when appropriate, specialist
      referral may be necessary to appropriately assess and treat these patients.

PMID- 21068533
TI  - Optimizing inpatient glycemic control with basal-bolus insulin therapy.
AB  - Hyperglycemia is highly prevalent in the acute-care setting and is associated
      with an increased risk of morbidity and mortality. Evidence suggests that
      glycemic control in this population is suboptimal, due in part to continued use
      of nonphysiologic sliding-scale insulin strategies without scheduled basal
      insulin doses or prandial insulin with concomitant correction doses. Although the
      ineffectiveness and risks of sliding-scale insulin regimens have been criticized
      for decades, sliding-scale insulin is still the most commonly prescribed
      subcutaneous insulin regimen among inpatients. Improving inpatient management
      requires the use of scheduled basal-bolus insulin therapy that includes basal
      insulin, nutritional insulin, and supplemental, or correctional, insulin. Insulin
      analogs are the preferred insulins, as they provide a more physiologic action
      than human insulin regimens, are associated with a lower risk of hypoglycemia,
      and are more convenient to administer than human insulins. Standardized insulin
      protocols and subcutaneous insulin order sets are critical components of
      effective inpatient glycemic control. Although preliminary data have demonstrated
      that inpatient diabetes management programs involving basal-bolus insulin therapy
      are effective and well tolerated, more research is needed.

PMID- 21068534
TI  - Antimicrobial resistance in Hispanic patients hospitalized in San Antonio, TX
      with community-acquired pneumonia.
AB  - Limited information is available on the antimicrobial resistance of patients with
      community-acquired pneumonia (CAP) depending on their ethnicity. Our aim was to
      compare the clinical characteristics, etiology, and microbiological resistance of
      Hispanic versus non-Hispanic white patients. A retrospective cohort of 601
      patients with a diagnosis of CAP included 288 non-Hispanic whites and 313
      Hispanics. Penicillin-resistant Streptococcus pneumoniae was more common among
      Hispanic patients (21.7% vs 0%; P=0.03) but there were no significant differences
      in macrolide-resistant S pneumoniae, drug-resistant S pneumoniae, or potential or
      actual multidrug-resistant pathogens (eg, drug-resistant S pneumoniae,
      methicillin-resistant Staphylococcus aureus, Pseudomonas spp., and Acinetobacter
      spp.). There were no differences among groups in length of hospital stay,
      intensive care unit (ICU) admission, or 30-day mortality. This study suggests
      that Hispanic patients with CAP have a higher rate of penicillin-resistant S
      pneumoniae, but no differences in antimicrobial resistance, 30-day mortality, ICU
      admission, or length of stay when compared with non-Hispanic white patients.

PMID- 21068535
TI  - Integrating CUSP and TRIP to improve patient safety.
AB  - Despite increased awareness of the risks to patients within the health care
      system, there has been little improvement in patient safety, with 1 in 7 patients
      experiencing an adverse event during hospitalization. Patients are exposed to
      harm not only through medical errors but also by physicians' failure to adhere to
      evidence-based best practices, as patients receive recommended therapies only
      half of the time. Although much research has been devoted to developing new
      therapies, little time has been spent investigating the science of health care
      delivery. We developed 2 models for improving health care delivery that have been
      successfully utilized in the Michigan Keystone Project to eliminate catheter
      related bloodstream infections. The first is the Comprehensive Unit-Based Safety
      Program (CUSP), which is aimed at changing the culture of safety and provides a
      framework for addressing patient safety issues at a local level. CUSP takes
      advantage of local wisdom to identify potential patient harms and create
      individualized solutions. The second is the Translating Evidence Into Practice
      (TRIP) model, which evaluates best practices at a hospital or hospital system
      level, and then creates strategies for implementation at a local level. TRIP
      seeks to identify barriers to implementation of best-practice medicine and
      standardize care over multiple care units. Components of the 2 programs are not
      mutually exclusive and both can be used to mitigate potential patient harms.

PMID- 21068536
TI  - Probiotics in gastrointestinal disorders.
AB  - A new era in medical science has dawned with the realization of the critical role
      of the "forgotten organ," the enteric flora, in health and disease. Central to
      this beneficial interaction between the flora and humans is the manner in which
      the bacteria contained within the gut "talk" to the immune system and, in
      particular, the immune system that is widespread within the gut itself, the gut-
      (or mucosa-) associated lymphoid tissue (GALT or MALT). Into this landscape comes
      a new player: the probiotic. While many products have masqueraded as probiotics,
      only those that truly and reproducibly contain live organisms and have been
      shown, in high-quality human studies, to confer a health benefit can actually
      claim this title. Several human disease states have benefited from the use of
      probiotics, most notably diarrheal illnesses, some inflammatory bowel diseases,
      and certain infectious disorders. Irritable bowel syndrome can now be added to
      this list. Although this area holds much promise, more high-quality trials of
      probiotics in digestive disorders, as well as laboratory investigations of their
      mechanisms of action, are required.

PMID- 21068537
TI  - Appropriate VTE prophylaxis is associated with lower direct medical costs.
AB  - PURPOSE: To calculate and compare the direct medical costs of guideline
      recommended prophylaxis with prophylaxis that does not fully adhere with
      guideline recommendations in a large, real-world population. METHODS: Discharge
      records were retrieved from the US Premier PerspectiveTM database (January 2003
      December 2003) for patients aged>=40 years with a primary diagnosis of cancer,
      chronic heart failure, lung disease, or severe infectious disease who received
      some form of thromboprophylaxis. Univariate analysis and multivariate regression
      modeling were performed to compare direct medical costs between discharges who
      received appropriate prophylaxis (correct type, dose, and duration based on sixth
      edition American College of Chest Physicians [ACCP] recommendations) and partial
      prophylaxis (not in full accordance with ACCP recommendations). Market
      segmentation analysis was used to compare costs stratified by hospital and
      patient characteristics. RESULTS: Of the 683 005 discharges included, 148,171
      (21.7%) received appropriate prophylaxis and 534,834 (78.3%) received partial
      prophylaxis. The total direct unadjusted costs were $15,439 in the appropriate
      prophylaxis group and $17,763 in the partial prophylaxis group. After adjustment,
      mean adjusted total costs per discharge were lower for those receiving
      appropriate prophylaxis ($11,713; 95% confidence interval [CI], $11,675-$11,753)
      compared with partial prophylaxis ($13,369; 95% CI, $13,332-$13 406; P<0.01).
      Appropriate prophylaxis appeared to be associated with numerically lower
      unadjusted costs than partial prophylaxis, regardless of hospital size,
      rural/urban location, teaching status, and patient age and gender. CONCLUSION:
      This large, real-world analysis suggests that appropriate prophylaxis, in
      adherence with ACCP guidelines, is potentially cost-saving compared with partial
      prophylaxis in at-risk medical patients.

PMID- 21068538
TI  - Economic impact of switching to bivalirudin for a primary percutaneous coronary
      intervention in a US hospital.
AB  - BACKGROUND: The addition of glycoprotein IIb/IIIa inhibitors (GPIs) to heparin in
      percutaneous coronary intervention (PCI) procedures has been demonstrated to
      reduce ischemic complications; however, GPI use is known to increase the risk of
      bleeding events, which are linked to increased mortality, longer hospital length
      of stay, greater medical resource utilization, and increased costs. New
      antithrombotic therapies have the potential to improve clinical outcomes and
      decrease costs. The Harmonizing Outcomes with Revascularization and Stents in
      Acute Myocardial Infarction (HORIZONS-AMI) study of bivalirudin demonstrated
      significantly reduced clinical event rates (mortality and bleeding) compared with
      an unfractionated heparin (UFH)+GPI regimen. OBJECTIVE: The potential clinical
      and economic value of implementing a bivalirudin-based strategy for ST-segment
      elevation myocardial infarction (STEMI) patients receiving primary PCI (PPCI) is
      compared with current UFH+GPI-based practice from a US hospital perspective.
      METHODS: A budget impact model was developed to compare treatment of STEMI
      patients undergoing PPCI with a bivalirudin- or UFH+GPI-based strategy. Clinical
      data for the model were derived from the HORIZONS-AMI trial, and included 30-day
      event rates for major complications (eg, protocol bleeding, Q-wave MI, repeat
      PCI, and coronary artery bypass graft procedures). United States cost data and
      clinical practice data were derived from a Premier PerspectiveTM database
      analysis and published sources. RESULTS: Overall, average procedure costs per
      UFH+GPI-treated patient were $18,561. Treating patients with bivalirudin
      (incorporating 7.2% provisional GPI use per HORIZONS-AMI) may save $1690 per
      patient (average procedural cost, $16,872). In extrapolating these benefits to
      the American College of Cardiology/American Heart Association recommended
      institutional minimum of 36 PPCIs annually, 1 major bleeding event (3.7%) and 3
      minor bleeding events (6.8%) could be averted with use of bivalirudin. In
      addition, introducing a bivalirudin-based strategy to treat a minimum cohort of
      36 STEMI patients would save the hospital budget $60,807 (9%) per year.
      CONCLUSION: Using a bivalirudin-based strategy in STEMI patients undergoing PPCI
      is associated with favorable clinical and economic outcomes when compared with an
      UFH+GPI-based strategy in a US hospital setting.

PMID- 21068540
TI  - CIP2A expression and localization in oral carcinoma and dysplasia.
AB  - AIMS: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the
      oral cavity resulting in severe morbidity and mortality. To date only few
      proteins have been suggested as potential biomarkers or targets for this type of
      cancer. Cancerous inhibitor of PP2A (CIP2A) is a protein expressed in epithelial
      tissues that stabilizes the oncogene c-Myc and causes cell transformation. This
      study was designed to investigate the expression of CIP2A in OSCC cell lines and
      tissues representing human normal, dysplasia and OSCC. METHODS: Using
      quantitative real time PCR, mRNA quantification for CIP2A was performed in a
      primary gingival cell line and OSCCs CAL 27 and SCC-25. Paraffin embedded human
      specimen classified as normal, dysplastic or OSCC were immunohistochemically
      stained for CIP2A expression. EGFR and CIP2A were also stained by
      immunofluorescence for co-localization. Samples of human normal oral tissue and
      OSCC were studied by PCR for mRNA expression of CIP2A. RESULTS: CIP2A was
      significantly increased in the human carcinoma cell lines compared to the primary
      gingival cell line. CIP2A was overexpressed in the human oral dysplasia and OSCC
      tissues compared to normal oral tissues. CIP2A was also preferentially localized
      in the dysplastic and OSCC epithelial areas compared to EGFR that was expressed
      mainly in areas of relatively normal epithelium and in dysplastic tissues above
      the basal layers. CONCLUSIONS: CIP2A may play a significant role in oral
      malignant transformation and therefore, it may be a potential target for
      chemotherapy of OSCC.

PMID- 21068541
TI  - DAMP-mediated autophagy contributes to drug resistance.
AB  - Damage-associated molecular pattern molecules (DAMPs) are cellularly derived
      molecules that can initiate and perpetuate immune responses following trauma,
      ischemia and other types of tissue damage in the absence of pathogenic infection.
      High mobility group box 1 (HMGB1) is a prototypical DAMP and is associated with
      the hallmarks of cancer. Recently we found that HMGB1 release after chemotherapy
      treatment is a critical regulator of autophagy and a potential drug target for
      therapeutic interventions in leukemia. Overexpression of HMGB1 by gene
      transfection rendered leukemia cells resistant to cell death; whereas depletion
      or inhibition of HMGB1 and autophagy by RNA interference or pharmacological
      inhibitors increased the sensitivity of leukemia cells to chemotherapeutic drugs.
      HMGB1 release sustains autophagy as assessed by microtubule-associated protein 1
      light chain 3 (LC3) lipidation, redistribution of LC3 into cytoplasmic puncta,
      degradation of p62 and accumulation of autophagosomes and autolysosomes.
      Moreover, these data suggest a role for HMGB1 in the regulation of autophagy
      through the PI3KC3-MEKERK: pathway, supporting the notion that HMGB1-induced
      autophagy promotes tumor resistance to chemotherapy.

PMID- 21068542
TI  - Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes
      during autophagy.
AB  - Atg9 is a transmembrane protein essential for autophagy which cycles between the
      Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells
      during starvation through a mechanism that is dependent on ULK1 and requires the
      activity of the class III phosphatidylinositol-3-kinase (PI3KC3). In this study,
      we demonstrate that the N-BAR-containing protein, Bif-1, is required for Atg9
      trafficking and the fission of Golgi membranes during the induction of autophagy.
      Upon starvation, Atg9-positive membranes undergo continuous tubulation and
      fragmentation to produce cytoplasmic punctate structures that are positive for
      Rab5, Atg16L and LC3. Loss of Bif-1 or inhibition of the PI3KC3 complex II
      suppresses starvation-induced fission of Golgi membranes and peripheral
      cytoplasmic redistribution of Atg9. Moreover, Bif-1 mutants, which lack the
      functional regions of the N-BAR domain that are responsible for membrane binding
      and/or bending activity, fail to restore the fission of Golgi membranes as well
      as the formation of Atg9 foci and autophagosomes in Bif-1-deficient cells starved
      of nutrients. Taken together, these findings suggest that Bif-1 acts as a
      critical regulator of Atg9 puncta formation presumably by mediating Golgi fission
      for autophagosome biogenesis during starvation.

PMID- 21068543
TI  - Principal investigators weigh in.

PMID- 21068544
TI  - ATG12-ATG3 and mitochondria.

PMID- 21068545
TI  - Internal working models of parenting: motivations of parents of infants with a
      congenital heart defect.
AB  - Drawing on attachment-caregiving theory, we interviewed parents of 24 infants
      with a complex congenital heart defect (CCHD) about parenting motivations through
      the first year. Using directed content analysis, 8 categories of motivations,
      focused either on the baby, the parent-infant relationship, family, self, or
      tasks were identified at 1, 4 or 6, and 12 months. A matrix of motivations by
      parent showed family and infant age variations. Motivations illustrated for 5
      parents at 1 month suggest that specification of expectations and intentions and
      clustering of motivations mentioned by a parent would advance study of linkages
      of parenting internal working models with parenting action.

PMID- 21068546
TI  - Belonging among newcomer youths: intersecting experiences of inclusion and
      exclusion.
AB  - Belonging has been identified as an important resource for health and well-being
      in the lives of youths. Thus, it is an important concept for upstream health
      promotion and culturally safe and relevant nursing care. While many researchers
      acknowledge the importance of the social, cultural, and political context in the
      lives of newcomer youths, little research has examined the sociopolitical
      processes inherent in immigrant and refugee youths' experiences of belonging. By
      employing an intersectional and postcolonial perspective, this study explored
      newcomer youths' gendered, racialized, and class experiences of inclusion and
      exclusion that ultimately influenced their sense of belonging in their country of
      resettlement. Through an examination of online blogs in the United States, the
      United Kingdom, Australia, and secondary analyses of transcribed interviews from
      a previous study conducted in Canada, experiences of belonging were revealed to
      be shaped by complex and multifaceted structures of oppression. Through
      individual and collective efforts of resistance and resiliency, newcomer youths
      worked to construct a sense of belonging in their daily lives. Despite these
      participants' demonstrated strengths, it is evident that more work is needed to
      support newcomer youths' sense of belonging and well-being throughout
      resettlement. Implications for nursing practice and research are discussed.

PMID- 21068547
TI  - The essence of psychiatric nursing: redefining nurses' identity through moral
      dialogue about reducing the use of coercion and restraint.
AB  - In this article, we focus on core values of psychiatric nurses in relation to
      coercion and constraint. We analyze changes that took place in a project aiming
      at reducing coercion at a closed inpatient ward of a psychiatric hospital. Using
      the philosophy of Hans-Georg Gadamer and Margaret Urban Walker, we analyze both
      the process of moral changes through dialogue and the outcome in terms of new
      identities and moral responsibilities. We conclude that the project stimulated
      nurses to redefine their roles and develop a deeper intersubjective understanding
      of core values of their profession.

PMID- 21068548
TI  - Invitation to dialogue on nursing essentials.

PMID- 21068549
TI  - Network-focused nursing development of a new concept.
AB  - Network-focused nursing--a new concept--was generated in a grounded theory study
      of nurses, teenager and young adults with cancer and their significant others.
      This article explores and clarifies the concept to prevent it from being
      normalized and taken for granted in everyday clinical practice and in the
      literature, and from being limited in growth and meanings. The integrated
      approach by Meleis combined with the Hybrid Model by Schwartz-Barcott and Kim are
      used for analysis. Antecedents, attributes and consequences are identified.
      Network-focused nursing has potential to advance nursing science and to be
      implemented in other areas of patient care.

PMID- 21068550
TI  - More than vision: imagination as an elemental characteristic of being a nurse
      leader-mentor.
AB  - Mentoring relationships are dynamic alliances that can be used as a supportive
      mechanism for growing nurse leaders and promoting the future of the nursing
      profession. This article explores imagination as one of the central meanings of
      being a mentor for nursing leadership. Findings from a hermeneutic
      phenomenological study concerned with Australian nurse leaders' experiences and
      understandings of mentorship for leadership revealed that imagination was a key
      characteristic of being a nurse leader-mentor. Imagination that moved beyond
      fantasy to closely connect with reason was essential for nurse leader-mentors to
      recognize and activate the myriad possibilities available to mentees and the
      nursing profession more broadly.

PMID- 21068551
TI  - Self-awareness: a review and analysis of a basic nursing concept.
AB  - Self-awareness has long been addressed as fundamental for the professional nurse
      with the accepted view that self-awareness will lead to greater competence.
      Therefore, it is important to understand the historical evolution of the concept,
      attributes, antecedents, and consequences. Rodgers' evolutionary method was used
      for critical analysis of nursing, social sciences, and education literature.
      Analysis indicates that self-awareness is a dynamic, transformative process of
      self. Ultimately, self-awareness is the use of self-insights and presence
      knowingly to guide behavior that is genuine and authentic to create a healing
      interpersonal environment. Future research areas within practice and education
      are identified.

PMID- 21068552
TI  - The importance of being humble.
AB  - Scholarly work in philosophy, positive psychology, and other applied disciplines
      reconceptualize humility as an important element of reflection, change, and
      growth, but the change has not been mirrored in the nursing literature. Humility
      has a rich heritage and may be an implicit but fundamental construct in nursing.
      The value of humility for nursing education and practice rests in its conceptual
      basis for strategies that are currently being used. It is on the ground of
      humility that self-reflection, response to weaknesses and accomplishments, and
      our orientation to relationships should rest.

PMID- 21068553
TI  - The essential imperative of basic nursing education: an ethical discourse.
AB  - The presence of multiple educational pathways into professional nursing is not
      without ethical consequences. If the essential duty of nursing is to the patient
      then education must focus on teaching the highest provision of patient care. The
      humanities component of the baccalaureate provides both insight into the human
      condition and exposure to alternate problem-solving methodologies, both of which
      augment the nursing process and improve patient care. An argument is made that by
      not requiring more rather than less education, we ultimately fail the patient and
      thus, our ethical duty.

PMID- 21068554
TI  - Facilitating resilience using a society-to-cells framework: a theory of nursing
      essentials applied to research and practice.
AB  - The resilience potential of each human being is an essential focus of nursing
      care and research. An honored nursing tradition is viewing each patient in the
      context of family and culture and recognizing how these factors affect a
      patient's health and ability to be resilient. We present a society-to-cells
      nursing theory that formalizes and extends this holistic view of patients by
      delineating factors that contribute to resilience potential based on the society,
      community, and family environment in which people live, as well as individual
      variables that influence psychological, physiological, and cellular coping
      abilities. We also summarize how this perspective is essential to optimize
      patient care and to inform future nursing research.

PMID- 21068555
TI  - No essence no self: using a Buddhist perspective to characterize the nature of
      nursing.
AB  - A fresh perspective is needed on the historical roots and contemporary politics
      of the essentials of nursing. In the 21st century, the profession needs to move
      past separatist thinking and the pursuit of identifying what can be called a
      professional self. Two ways that nurses have tried to characterize a professional
      self is through claiming caring as the essence of nursing and using the esoteric
      taxonomy system of nursing diagnoses. The Buddhist teaching of nonself (anatman)
      is proposed as an alternative way of viewing the nature of the profession.

PMID- 21068556
TI  - Concept analysis of cognitive artifacts.
AB  - Cognitive artifacts--information displays that inform thought processes and
      increase knowledge--fulfill a fundamental role in distributed cognition.
      Cognitive work--the mental processes of selecting and evaluating data, reasoning,
      and making decisions--is guided and informed by cognitive artifacts, especially
      in clinical areas. The importance of cognitive artifacts to cognitive work
      suggests the need to study and comprehensively understand cognitive artifacts
      prepared and used by the clinical nurses and how these documents influence and
      guide nursing practice. This article identifies and describes the attributes of
      effectively constructed cognitive artifacts using the concept analysis process
      described by Walker and Avant.

PMID- 21068557
TI  - Tradition meets technology: building caring community online.
AB  - Community has historically provided an essential psycho-spiritual framework for
      nursing. Changes in communication technology pose challenges for nurses
      internationally who create communities across borders. This article discusses The
      Bamboo Bridge online community, a project responding to the global call for
      nursing education about the complementarity of nursing and healing traditions.
      The project explores how technologies such as Centra and Ning promote community
      building and encourage belonging in members from 5 continents and 10 countries.
      This article includes detailed accounts of the project design, examples of
      cultural diplomacy as the emerging theoretical framework, and an African member's
      perspective of online community.

PMID- 21068560
TI  - Youth sports: who's pushing the cart?

PMID- 21068561
TI  - An outbreak of muscle breakdown: a morality play in four acts.

PMID- 21068563
TI  - The adolescent knee and risk for osteoarthritis - an opportunity or
      responsibility for sport medicine physicians?

PMID- 21068564
TI  - Iliac artery flow limitations in endurance athletes.

PMID- 21068565
TI  - Vital signs and demographics in the preparticipation sports exam: do they help us
      find the elusive athlete at risk for sudden cardiac death?
AB  - Much attention recently has been paid to the detection of those young athletes
      who may be at risk for sudden cardiac death (SCD) in sports participation. In
      this article, we attempt to summarize the remarkably few studies that examine the
      question of whether vital signs and basic demographics are associated with
      athletes at risk for SCD. Historical items such as chest pain, dyspnea, and
      palpitations are not reviewed. The only demographics mentioned in the literature
      as associated with SCD are being of the male gender, which is associated highly
      with SCD, and being African-American. Most notably, we were unable to find even
      prospective data asking the question of whether resting pulse, blood pressure,
      height, weight, and age are potential risk factors. Therefore, we also have
      included recent data from our own research to make this summary more complete.

PMID- 21068566
TI  - Factors that prevent roughstock rodeo athletes from wearing protective equipment.
AB  - Using a cross-sectional survey design, this study sought to determine usage rates
      and barriers to the use of protective equipment in roughstock athletes. Between
      2004 and 2006, amateur, collegiate, and professional roughstock athletes were
      surveyed using national organizational mailing lists. Findings revealed that
      during competition, 69% never wore a helmet. Barriers were a negative effect on
      performance and sport persona. Conversely, 88% always wore a vest. The perception
      that vest usage was required encouraged roughstock athletes to wear them.
      Mouthpiece use results were mixed; 58% always used and 21% never used a
      mouthpiece. Barriers were discomfort and frequent forgetfulness. Reported injury
      rate was high, with users noting fewer injuries to head and ribs than nonusers,
      and riders agreed that protective equipment prevented injury to the head, ribs,
      and mouth. However, equipment usage rates varied widely by type and seemed to be
      underutilized because the equipment affected performance, was uncomfortable, and
      "not cowboy."

PMID- 21068567
TI  - Sickle cell trait in sports.
AB  - Sickle cell trait (SCT) can pose a grave risk for some athletes. In the past
      decade in NCAA Division I football, no deaths have occurred from the play or
      practice of the game, but 16 deaths have occurred from conditioning for the game,
      and 10 (63%) of these deaths are tied to SCT, an excess of up to 21-fold.
      Research shows how and why, during intense exercise bouts, sickle cells can
      accumulate and "logjam" blood vessels, causing explosive rhabdomyolysis that can
      kill. Sickling can begin in 2 to 5 min of all-out exertion and can reach grave
      levels soon thereafter if the athlete struggles on or is urged on by coaches
      despite warning signs. Sickling collapse is an intensity syndrome that differs
      from other common causes of collapse. Tailored precautions can prevent sickling
      collapse and enable athletes with SCT to thrive. Irrationally intense
      conditioning for a game puts the lives of healthy athletes with SCT at risk.

PMID- 21068568
TI  - Bone density in competitive cyclists.
AB  - To investigate current theories of the contributing factors to
      osteopenia/osteoporosis in competitive cyclists, we present a narrative review of
      published cross-sectional studies investigating plausible etiologies of decreased
      bone density in competitive cyclists. Aggregate from multiple published studies
      as cited. Bone mineral density in cyclists appears to be correlated positively to
      the cumulative amount of bone loading forces experienced over a lifetime.
      However, decreases in bone mineral density are noted over the short term if bone
      loading forces are removed, despite previous gains. There also appears to be a
      negative correlation between bone mineral density and dermal calcium losses
      during exercise. Data are mixed on whether calcium supplementation improves bone
      mineral density in this setting. No correlation was found between sex hormones
      and bone mineral density in the competitive cyclists studied. Knowledge of the
      underlying contributors to reduced bone mineral density in cyclists can aid in
      making preventative and therapeutic recommendations that potentially could
      decrease the morbidity and mortality related to osteoporosis.

PMID- 21068569
TI  - The young athlete: challenges of growth, development, and society.
AB  - Youth sports provide numerous health-enhancing and other important benefits to
      participating children and adolescents. However, the motivations and goals of
      young athletes often conflict with those of adult stakeholders, and they are
      redirected. The youth sports industry has become exclusionary, as the
      professional model of development increasingly is prevalent and accepted. Youth
      who follow this model often cannot keep up with the unrealistic expectations and
      excessive demands. Too much play, training, travel, and pressure frequently lead
      to a variety of physical and psychological problems, particularly concurrent with
      the vulnerability of a young athlete going through pre- or early adolescence and
      the rapid growth phase. The need for alternative models, emphasizing fun and
      fundamentals, is becoming increasingly clear and urgent. With appropriate
      changes, youth sports once again can be an effective entry point for a lifetime
      of healthy sports participation and enjoyment.

PMID- 21068570
TI  - Competitive youth sports in society: what President Obama needs to know to get -
      and keep - kids moving.
AB  - In February 2010, President Obama created the Child Obesity Task Force to address
      the problem that nearly one in three children in the United States are overweight
      or obese. In May, the Task Force released its action plan, the goal of which is
      to return to the obesity rate of just 5% by 2030, the level it was until the
      1970s. These recommendations are helpful but incomplete. To help get kids off the
      couch, President Obama and other leaders need to understand and confront today's
      culture of organized youth sports, which often dominates the facilities and play
      resources available to children and teens.

PMID- 21068571
TI  - Early sport specialization: roots, effectiveness, risks.
AB  - Year-round training in a single sport beginning at a relatively young age is
      increasingly common among youth. Contributing factors include perceptions of
      Eastern European sport programs, a parent's desire to give his or her child an
      edge, labeling youth as talented at an early age, pursuit of scholarships and
      professional contracts, the sporting goods and services industry, and expertise
      research. The factors interact with the demands of sport systems. Limiting
      experiences to a single sport is not the best path to elite status. Risks of
      early specialization include social isolation, overdependence, burnout, and
      perhaps risk of overuse injury. Commitment to a single sport at an early age
      immerses a youngster in a complex world regulated by adults, which is a setting
      that facilitates manipulation - social, dietary, chemical, and commercial. Youth
      sport must be kept in perspective. Participants, including talented young
      athletes, are children and adolescents with the needs of children and
      adolescents.

PMID- 21068572
TI  - Evaluation of overuse injuries in children and adolescents.
AB  - With the increasingly competitive nature of many youth sports and with single
      sport specialization occurring at young ages, overuse injuries are common among
      young athletes. Several growth-related factors contribute to the development of
      overuse injuries in children and adolescents, including the susceptibility of
      growth cartilage to injury and the adolescent growth spurt. This article will
      discuss these unique factors and provide an overview of the diagnosis and
      treatment of overuse injuries in this age group. Specific measures aimed at
      preventing overuse injuries in young athletes also will be presented.

PMID- 21068573
TI  - Long-term athlete development Canada: attempting system change and multi-agency
      cooperation.
AB  - This text provides a synopsis, as well as some greater detail, concerning the
      "Canadian Sport for Life" project Long-Term Athlete Development Canada (LTAD)
      initiated in 2004. The genesis of the project may be found in the Canadian Sport
      Policy released in 2002 by Sport Canada, the sport participation and performance
      agency within the Canadian Heritage Ministry of the Canadian Government. The
      project has grown from relatively humble beginnings to become a system-wide
      movement and catalyst for change that encompasses not only sport participation
      and excellence, but also aspects to do with education, health, and general
      recreation. Additionally, it involves all age groups (cradle to grave). Although
      the project was initiated on behalf of performance sport, it is a clear example
      of how sport can influence and interact with many facets of a society. In Canada,
      LTAD clearly is tied to a philosophy that spans a broad narrative from healthy
      active lives to elite sport performance.

PMID- 21068575
TI  - European Society of Gastrointestinal Endoscopy, European Society of
      Gastroenterology and Endoscopy Nurses and Associates, and the European Society of
      Anaesthesiology Guideline: Non-anaesthesiologist administration of propofol for
      GI endoscopy.
AB  - Propofol sedation by non-anaesthesiologists is an upcoming sedation regimen in
      several countries throughout Europe. Numerous studies have shown the efficacy and
      safety of this sedation regimen in gastrointestinal endoscopy. Nevertheless, this
      issue remains highly controversial. The aim of this evidence- and consensus-based
      set of guideline is to provide non-anaesthesiologists with a comprehensive
      framework for propofol sedation during digestive endoscopy. This guideline
      results from a collaborative effort from representatives of the European Society
      of Gastrointestinal Endoscopy (ESGE), the European Society of Gastroenterology
      and Endoscopy Nurses and Associates (ESGENA) and the European Society of
      Anaesthesiology (ESA). These three societies have endorsed the present
      guideline.The guideline is published simultaneously in the Journals Endoscopy and
      European Journal of Anaesthesiology.

PMID- 21068576
TI  - Comment on the impact of gene patents and licensing practices on access to
      genetic testing: lessons from hereditary hemorrhagic telangiectasia.

PMID- 21068577
TI  - Response to ACMG Practice Guidelines and ACMG Standards and Guidelines, Genetics
      in Medicine, July 2010, volume 12, number 7, pages 446-463 and 464-470.

PMID- 21068581
TI  - 2010 Elda E. Anderson Award.

PMID- 21068582
TI  - 2010 Robley D. Evans commemorative medal.

PMID- 21068583
TI  - 2010 H. Wade Patterson Memorial Award.

PMID- 21068584
TI  - 2010 Lutz Moritz Memorial Award.

PMID- 21068586
TI  - 2010 Geoffrey G. Eichholz outstanding science teacher award.

PMID- 21068588
TI  - Lutz E. Moritz.

PMID- 21068590
TI  - 2010 Arthur F. Humm Jr. Award.

PMID- 21068591
TI  - 2010 William A. McAdams outstanding service award.

PMID- 21068592
TI  - 2010 the Joyce P. Davis memorial Davis Award.

PMID- 21068593
TI  - Checking the foundation: recent radiobiology and the linear no-threshold theory.
AB  - The linear no-threshold (LNT) theory has been adopted as the foundation of
      radiation protection standards and risk estimation for several decades. The
      "microdosimetric argument" has been offered in support of the LNT theory. This
      argument postulates that energy is deposited in critical cellular targets by
      radiation in a linear fashion across all doses down to zero, and that this in
      turn implies a linear relationship between dose and biological effect across all
      doses. This paper examines whether the microdosimetric argument holds at the
      lowest levels of biological organization following low dose, low dose-rate
      exposures to ionizing radiation. The assumptions of the microdosimetric argument
      are evaluated in light of recent radiobiological studies on radiation damage in
      biological molecules and cellular and tissue level responses to radiation damage.
      There is strong evidence that radiation initially deposits energy in biological
      molecules (e.g., DNA) in a linear fashion, and that this energy deposition
      results in various forms of prompt DNA damage that may be produced in a pattern
      that is distinct from endogenous (e.g., oxidative) damage. However, a large and
      rapidly growing body of radiobiological evidence indicates that cell and tissue
      level responses to this damage, particularly at low doses and/or dose-rates, are
      nonlinear and may exhibit thresholds. To the extent that responses observed at
      lower levels of biological organization in vitro are predictive of carcinogenesis
      observed in vivo, this evidence directly contradicts the assumptions upon which
      the microdosimetric argument is based.

PMID- 21068594
TI  - Error analysis for the in-vivo measurement of radionuclides in wounds: Monte
      Carlo study.
AB  - This paper describes calculation of error associated with the direct in-vivo
      measurements of radionuclides in a wound. A typical radiation injury to a hand
      with Am radionuclide is illustrated for error analysis. A Monte Carlo model was
      developed and the detector pulse spectrum studied with a custom-designed HPGe
      detector. A pinhole collimator was designed, and its performance with a wide area
      detector was studied. The results show that significant errors might propagate if
      the lowest energy peaks of Am are used during in vivo measurements of the wound.
      In comparison to that, less uncertainty was found for 26.3 and 59.5 keV gamma
      peaks, and those levels are recommended for estimation of wound depth and
      activity.

PMID- 21068595
TI  - Mathematical modeling of the radiation dose received from photons passing over
      and through shielding walls in a PET/CT suite.
AB  - Given that the financial cost of shielding PET/CT suites can be substantial, it
      has become increasingly important to be able to accurately assess the thickness
      of shielding required for barriers and whether it is necessary to extend such
      shielding all the way to the ceiling. The overall shielding requirement for a
      PET/CT installation must take into account both 511 keV gamma ray emissions from
      PET scans and lower energy x-ray scatter from CT scans. This paper deals with the
      overall impact of emissions from both modalities. Radiation exposure from both
      scatter over shielding barriers as well as transmission through these barriers is
      taken into account. A series of simulations of the dose received by a person
      positioned behind a shielding barrier in a typical PET/CT scanning suite were
      carried out using both Monte Carlo and analytical models. The transmission
      through lead barriers was found to be very dependent on the geometry of the
      radiation source and the resulting energy spectrum of the emitted radiation. The
      transmission from a patient source was found to be around half of that from a
      small vial and also half of that reported previously using parallel beams of mono
      energetic radiation. For PET emissions, the dose from scatter over the barrier at
      waist height is relatively small but may have to be taken into account if the
      design dose limit is low. Shielding from floor to ceiling is probably not
      warranted in most instances for PET gamma emissions; in PET/CT installations,
      however, a thinner layer of shielding may need to extend to the ceiling of the
      imaging room to limit x-ray scatter over the wall from the CT unit.

PMID- 21068596
TI  - A method of determining accuracy and precision for dosimeter systems using
      accreditation data.
AB  - A study of the uncertainty of dosimeter results is required by the national
      accreditation programs for each dosimeter model for which accreditation is
      sought. Typically, the methods used to determine uncertainty have included the
      partial differentiation method described in the U.S. Guide to Uncertainty in
      Measurements or the use of Monte Carlo techniques and probability distribution
      functions to generate simulated dose results. Each of these techniques has
      particular strengths and should be employed when the areas of uncertainty are
      required to be understood in detail. However, the uncertainty of dosimeter
      results can also be determined using a Model II One-Way Analysis of Variance
      technique and accreditation testing data. The strengths of the technique include
      (1) the method is straightforward and the data are provided under accreditation
      testing and (2) the method provides additional data for the analysis of long-term
      uncertainty using Statistical Process Control (SPC) techniques. The use of SPC to
      compare variances and standard deviations over time is described well in other
      areas and is not discussed in detail in this paper. The application of Analysis
      of Variance to historic testing data indicated that the accuracy in a
      representative dosimetry system (Panasonic(r) Model UD-802) was 8.2%, 5.1%, and
      4.8% and the expanded uncertainties at the 95% confidence level were 10.7%,
      14.9%, and 15.2% for the Accident, Protection Level-Shallow, and Protection Level
      Deep test categories in the Department of Energy Laboratory Accreditation
      Program, respectively. The 95% level of confidence ranges were (0.98 to 1.19),
      (0.90 to 1.20), and (0.90 to 1.20) for the three groupings of test categories,
      respectively.

PMID- 21068597
TI  - Predicting induced radioactivity for the accelerator operations at the Taiwan
      Photon Source.
AB  - This study investigates the characteristics of induced radioactivity due to the
      operations of a 3-GeV electron accelerator at the Taiwan Photon Source (TPS).
      According to the beam loss analysis, the authors set two representative
      irradiation conditions for the activation analysis. The FLUKA Monte Carlo code
      has been used to predict the isotope inventories, residual activities, and
      remanent dose rates as a function of time. The calculation model itself is simple
      but conservative for the evaluation of induced radioactivity in a light source
      facility. This study highlights the importance of beam loss scenarios and
      demonstrates the great advantage of using FLUKA in comparing the predicted
      radioactivity with corresponding regulatory limits. The calculated results lead
      to the conclusion that, due to fairly low electron consumption, the radioactivity
      induced in the accelerator components and surrounding concrete walls of the TPS
      is rather moderate and manageable, while the possible activation of air and
      cooling water in the tunnel and their environmental releases are negligible.

PMID- 21068598
TI  - An analytic approach to double dosimetry algorithms in occupational dosimetry
      using energy dependent organ dose conversion coefficients.
AB  - Personnel dose in diagnostic radiology is often underestimated. Typically the
      effective dose E is estimated based on dosimeters worn underneath the protective
      clothing measuring the personal dose equivalent Hp(10). This one-spot-measurement
      systematically neglects the exposure to the unshielded organs in the head and
      neck region. In this paper, energy dependent double dosimetry algorithms in the
      range of 30-80 keV are derived using organ dose conversion coefficients. The
      doses of shielded organs are assigned to a single dosimeter in the anterior
      thoracic region (chest) underneath the apron (Hp,c,u), and the doses of the
      organs not shielded are assigned to another dosimeter placed on the front area of
      the neck over the protective garment (Hp,n,o) with E = a1 Hp,c,u(10) + a2
      Hp,n,o(10). Organs not completely shielded are categorized correspondingly. The
      coefficients a1 and a2 increase with higher energies up to 70 keV. The factors a2
      are clearly higher according to ICRP 103 (rather than ICRP 60) because ICRP 103
      considers additional organs in the head and neck region. According to ICRP 103, a
      conservative general algorithm with thyroid protection is E = 0.84 Hp,c,u(10) +
      0.051 Hp,n,o(10) and without thyroid protection E = 0.79 Hp,c,u(10) + 0.100
      Hp,n,o(10).

PMID- 21068599
TI  - Thermal response of tissues to millimeter waves: implications for setting
      exposure guidelines.
AB  - This Note discusses the implications of a simple model for the thermal response
      of tissue subject to irradiation with millimeter waves (30-300 GHz) for setting
      limits for safe exposure to this energy. The estimated thresholds for thermal
      pain and thermal injury from long-term (minutes) and short-term (seconds)
      exposures are compared with two major exposure guidelines, IEEE C95.1-2005 and
      ICNIRP limits. An Appendix describes the rationale for setting the "averaging
      times" in IEEE C95.1-2005.

PMID- 21068600
TI  - Proposed revision to the radiation dosimetry of 82Rb.
AB  - Three models for the biodistribution and dosimetry of 82Rb-chloride were reviewed
      and a proposal is made for the best dosimetry for this agent to be adopted. Data
      from three proposed biokinetic models for 82Rb-chloride were used to calculate
      dose estimates for the compound, and the results were compared. The blood content
      based model was found to produce dose estimates that were considered to be overly
      conservative, and a blood flow-based model, which showed good agreement with
      available measured data, was considered to be more reasonable. A new set of dose
      estimates for 82Rb-chloride, based on the blood flow-based kinetic model are
      suggested for general use.

PMID- 21068601
TI  - Guidelines for limiting exposure to time-varying electric and magnetic fields (1
      Hz to 100 kHz).

PMID- 21068605
TI  - Surgical treatment of injuries to the solid abdominal organs: a 50-year
      perspective from the Journal of Trauma.

PMID- 21068606
TI  - The pattern of thoracic trauma after suicide terrorist bombing attacks.
AB  - BACKGROUND: The worldwide escalation in the volume of suicide terrorist bombing
      attacks warrants special attention to the specific pattern of injury associated
      with such attacks. The goal of this study was to characterize thoracic injuries
      inflicted by terrorist-related explosions and compare pattern of injury to
      penetrating and blunt thoracic trauma. METHODS: Prospectively collected database
      of patients with chest injury who were admitted to Hadassah Hospital Level I
      trauma centre, in Jerusalem, Israel, from October 2000 to December 2005. Patients
      were divided into three groups according to the mechanism of injury: terrorist
      explosions (n = 55), gunshot wounds (GSW; n = 78), and blunt trauma (n = 747).
      RESULTS: There were many female victims after suicide bombing attacks (49.1%)
      compared with GSW (21.8%) and blunt trauma (24.6%; p = 0.009). The number of body
      regions injured was significantly higher in the terror group compared with the
      GSW and blunt groups (median, 4, 2, and 3, respectively, p < 0.0001). The pattern
      of chest injury after suicide bombing attacks was caused by a unique combination
      of the effects of the blast wave and penetrating shrapnel. More than half (52.7%)
      of the terror victims suffered from lung contusion and 25 (45.5%) required tube
      thoracostomy. Five patients (9.1%) underwent thoracotomy for lung lacerations (n
      = 3), injury to great vessels (n = 2), cardiac lacerations (n = 1), and
      esophageal injury (n = 1). Penetrating shrapnel was the mechanism of injury in
      all these cases. CONCLUSIONS: Injury inflicted by terrorist bombings causes a
      unique pattern of thoracic wounds. Victims are exposed to a combination of lung
      injury caused by the blast wave and penetrating injury caused by metallic
      objects.

PMID- 21068607
TI  - Helicopters and the civilian trauma system: national utilization patterns
      demonstrate improved outcomes after traumatic injury.
AB  - BACKGROUND: The role of helicopter transport (HT) in civilian trauma care remains
      controversial. The objective of this study was to compare patient outcomes after
      transport from the scene of injury by HT and ground transport using a national
      patient sample. METHODS: Patients transported from the scene of injury by HT or
      ground transport in 2007 were identified using the National Trauma Databank
      version 8. Injury severity, utilization of hospital resources, and outcomes were
      compared. Stepwise logistic regression was used to determine whether transport
      modality was a predictor of survival or discharge to home after adjusting for
      covariates. RESULTS: There were 258,387 patients transported by helicopter (16%)
      or ground (84%). Mean Injury Severity Score was higher in HT patients (15.9 +/-
      12.3 vs. 10.2 +/- 9.5, p < 0.01), as was the percentage of patients with Injury
      Severity Score >15 (42.6% vs. 20.8%; odds ratio [OR], 2.83; 95% confidence
      interval [CI], 2.76-2.89). HT patients had higher rates of intensive care unit
      admission (43.5% vs. 22.9%; OR, 2.58; 95% CI, 2.53-2.64) and mechanical
      ventilation (20.8% vs. 7.4%; OR, 3.30; 95% CI, 3.21-3.40). HT was a predictor of
      survival (OR, 1.22; 95% CI, 1.17-1.27) and discharge to home (OR, 1.05; 95% CI,
      1.02-1.07) after adjustment for covariates. CONCLUSIONS: Trauma patients
      transported by helicopter were more severely injured, had longer transport times,
      and required more hospital resources than those transported by ground. Despite
      this, HT patients were more likely to survive and were more likely to be
      discharged home after treatment when compared with those transported by ground.
      Despite concerns regarding helicopter utilization in the civilian setting, this
      study shows that HT has merit and impacts outcome.

PMID- 21068608
TI  - Hips can lie: impact of excluding isolated hip fractures on external benchmarking
      of trauma center performance.
AB  - BACKGROUND: Trauma centers (TCs) vary in the inclusion of patients with isolated
      hip fractures (IHFs) in their registries. This inconsistent case ascertainment
      may have significant implications on the assessment of TC performance and
      external benchmarking efforts. METHODS: Data were derived from the National
      Trauma Data Bank (2007-8.1). We included patients (aged 16 years or older) with
      Injury Severity Score value >= 9 who were admitted to Level I and II TCs. To
      ensure data quality, we limited the study to TC that routinely reported
      comorbidities and Abbreviated Injury Scale codes. IHF were defined as patients,
      aged 65 years or older, injured as a result of falls, with Abbreviated Injury
      Scale codes for hip fracture and without other significant injuries. TCs were
      stratified according to their reported inclusion of IHF in their registry.
      Observed-to-expected mortality ratios were used to rank TC performance first with
      and then, without the inclusion of patients with IHF. RESULTS: In total, 91,152
      patients in 132 TCs were identified; 5% (n = 4,448) were IHF. The proportion of
      IHF per TC varied significantly, ranging from 0% to 31%. When risk-adjusted
      mortality was evaluated, excluding patients with IHF had significant effects: 37%
      (n = 49) of TCs changed their performance rank by >= 3 (range, 1-25) and 12% of
      centers changed their performance quintile. The greatest change in rank
      performance was evident in centers that routinely include IHF in their
      registries. CONCLUSIONS: Given the fact that IHFs in the elderly significantly
      influence risk-adjusted outcomes and are variably reported by TCs, these patients
      should be excluded from subsequent benchmarking efforts.

PMID- 21068609
TI  - Does the trauma system protect against the weekend effect?
AB  - BACKGROUND: Occurrence on weekends or at night has been associated with poor
      outcomes for time-sensitive conditions including ST elevation myocardial
      infarction, stroke, and cardiac arrest. We sought to determine whether the
      "weekend effect" exists for injured patients at our trauma center. METHODS: We
      performed a retrospective cohort study at a Level I trauma center (2006-2008).
      The relative risks of mortality associated with weekend or night arrival were
      estimated using unadjusted and adjusted analyses. RESULTS: Four thousand three
      hundred eighty-two patients were included. One-third of patients (34.0%) arrived
      on weekends, and 23.3% of patients arrived at night (12:00 midnight to 6:00 am).
      Average age was 43.2 years (44.2 weekdays vs. 41.4 weekends, p < 0.001 and 45.1
      days vs. 37.5 nights, p < 0.001), 72.3% were men (72.6 weekdays vs. 71.8
      weekends, p = not significant (NS) and 71.0% days vs. 76.8% nights, p < 0.001),
      overall Injury Severity Score was 13.7 (13.7 weekdays vs. 13.6 weekends, p = NS
      and 13.7 days vs. 13.3 nights, p = NS), and overall Glasgow Coma Scale score was
      13.6 (13.5 weekdays vs. 13.6 weekends, p = NS and 13.7 days vs. 13.4 nights, p <
      0.05). In unadjusted analyses, no survival difference was detected for patients
      presenting on weekends (5.2% vs. 5.3%; odds ratio [OR], 0.98; and 95% confidence
      interval [CI], 0.75-1.28) or at night (4.4% vs. 5.5%; OR, 0.81; and 95% CI, 0.58
      1.11). In adjusted analyses controlling for age, sex, Injury Severity Score,
      Glasgow Coma Scale score, and arrival hypotension, no survival difference was
      detected on weekends (OR, 1.03 and 95% CI, 0.71-1.51) or at night (OR, 0.79 and
      95% CI, 0.49-1.25). CONCLUSION: Differential mortality on off-hours is not seen
      at our Level I trauma center. Outcomes that are independent of time of day and
      day of week may be because of the explicit requirements for trauma centers to be
      fully staffed and operational at all times. There are implications for staffing
      and systems solutions for other time-sensitive disease including ST elevation
      myocardial infarction, stroke, and cardiac arrest. Interventions may include the
      development of a categorization system based on emergency care capabilities,
      development of explicit staffing requirements, and requiring an emergency care
      specific quality improvement program.

PMID- 21068610
TI  - "Damage control" in the elderly: futile endeavor or fruitful enterprise?
AB  - BACKGROUND: Damage control laparotomy (DCL) provides effective management in
      carefully selected, exsanguinating trauma patients. However, the effectiveness of
      this approach has not been examined in the elderly. The purpose of this study was
      to characterize elderly DCL patients. METHODS: The National Trauma Registry of
      the American College of Surgeons was queried for patients admitted to our Level I
      trauma center between January 2003 and June 2008. Patients who underwent a DCL
      were included in the study. Elderly (55 years or older) and young (16-54 years)
      patients were compared for demographics, injury severity, intraoperative
      transfusion volume, complications, and mortality. RESULTS: During the study
      period, 62 patients met inclusion criteria. Elderly and young cohorts were
      similar in gender (male, 78.6% vs. 75.0%, p = 0.78), Injury Severity Score (25.1
      +/- 2.1 vs. 23.8 +/- 1.7, p = 0.49), packed red blood cell transfusion volume
      (3036 mL +/- 2760 mL vs. 2654 mL +/- 2194 mL, p = 0.51), and number of
      complications (3.21 +/- 0.48 vs. 3.33 +/- 0.38, p = 0.96). Mortality was greater
      in the elderly cohort (42.9% vs. 12.5%, p = 0.02). The mean time to death for the
      elderly was 9.8 days +/- 10.2 days and 26 days +/- 21.5 days in the young (p =
      0.485). CONCLUSIONS: Despite the severity of injury, the outcome of elderly DCL
      patients is better than what might be predicted. They succumb to their injuries
      more frequently and earlier in the hospital course compared with the young, but
      the majority of these patients survive. DCL in the elderly is not a futile
      endeavor.

PMID- 21068611
TI  - Red blood cells accelerate the onset of clot formation in polytrauma and
      hemorrhagic shock.
AB  - BACKGROUND: Hemorrhage and coagulopathy are major contributors to death after
      trauma. The contribution of red blood cells (RBCs) in correcting coagulopathy is
      poorly understood. Current methods of measuring coagulopathy may fail to
      accurately characterize in vivo clotting. We aimed to determine the effect of
      RBCs on clotting parameters by comparing resuscitation regimens containing RBCs
      and plasma with those containing plasma alone. METHODS: Thirty-two Yorkshire
      swine were anesthetized, subjected to a complex model of polytrauma and
      hemorrhagic shock, and resuscitated with either fresh frozen plasma, lyophilized
      plasma (LP), or 1:1 ratios of fresh frozen plasma:packed RBC (PRBC) or LP:PRBC.
      Activated clotting time, prothrombin time, partial thromboplastin time, and
      thrombelastography (TEG) were performed at 1 hour, 2 hours, 3 hours, and 4 hours
      after resuscitation. RESULTS: Animals treated with 1:1 LP:PRBC had less blood
      loss than the other groups (p < 0.05). The activated clotting time was shorter in
      the 1:1 groups when compared with the pure plasma groups at all time points (p <
      0.05). The 1:1 groups had shorter TEG R times (time to onset of clotting) at 1
      hour, 3 hours, and 4 hours compared with pure plasma groups (p < 0.05). Other TEG
      parameters did not differ between groups. Partial thromboplastin time was shorter
      in the pure plasma groups than the 1:1 groups at all time points (p < 0.05).
      CONCLUSIONS: Whole blood assays reveal that RBCs accelerate the onset of clot
      formation. Coagulation assays using spun plasma underestimate the effect of RBCs
      on clotting and do not completely characterize clot formation.

PMID- 21068612
TI  - Clot-inducing minerals versus plasma protein dressing for topical treatment of
      external bleeding in the presence of coagulopathy.
AB  - BACKGROUND: Previous studies identified WoundStat (WS, smectite) and Combat Gauze
      (CG, kaolin-coated gauze) as the most effective available agents for controlling
      arterial bleeding with potential utility in casualty care. Tissue sealant
      properties of WS suggested its potential advantage over clot-promoting CG for
      treating coagulopathic bleeding. This study compared the efficacy of CG and WS
      with a fibrinogen-based (FAST) dressing to control bleeding in coagulopathic
      animals. METHODS: Coagulopathy was induced in pigs (n = 55, 35 kg) by ~50%
      isovolemic hemodilution and hypothermia (core temperature, 33 degrees C +/- 0.5
      degrees C). A 6-mm arteriotomy was made in the femoral artery and free bleeding
      allowed for 30 seconds. A test agent (n = 13-15 per group) or control product
      (gauze, GZ, n = 12) was applied to the wounds and compressed with a Kerlix gauze
      for 2 minutes. Fluid resuscitation was given, titrated to a mean arterial
      pressure of 65 mm Hg. Animals were observed for 180 minutes or until death.
      Angiography using the computed tomography method was performed on survivors, and
      local tissues were collected for histology. RESULTS: No differences were seen in
      baseline measures. Coagulopathy, confirmed by a 31% increase in prothrombin time
      and a 28% reduction in clotting strength (maximum amplitude, thrombelastography
      assay), was similar in all groups before injury. The average pretreatment blood
      loss was 11.9 mL/kg +/- 0.4 mL/kg with no difference among groups. Posttreatment
      blood loss, however, was significantly different (p = 0.015) ranging from 18.2
      mL/kg +/- 8.8 mL/kg (FAST) to 63.3 mL/kg +/- 10.2 mL/kg (GZ controls). Stable
      hemostasis was achieved in 10 of 13 (FAST), 5 of 15 (CG), 2 of 15 (WS), and 1 of
      12 (GZ) animals in each group, resulting in significantly different survival
      rates (8-77%; p = 0.001). The average survival times were 145 (FAST), 119 (CG),
      75 (WS), and 74 (GZ) minutes for different groups (p < 0.002). The outcomes with
      the FAST dressing were significantly better than with WS or GZ in this
      coagulopathic bleeding model. Essentially, no difference was found between WS and
      GZ control. Computed tomography images showed limited blood flow only through the
      vessels treated with FAST dressings. Histologic observations of the vessels
      indicated minimal damage with FAST and CG and greater injury with WS with some
      residues present on the tissues. CONCLUSION: The tissue sealant property of WS is
      apparently mediated by clot formation in the wound; therefore, it was ineffective
      under coagulopathic conditions. CG was partially effective in maintaining blood
      pressure up to 1 hour after application. FAST dressing showed the highest
      efficacy because of the exogenous delivery of concentrated fibrinogen and
      thrombin to the wound, which bypasses coagulopathy and secures hemostasis.

PMID- 21068613
TI  - Ventilator-associated pneumonia is more common and of less consequence in trauma
      patients compared with other critically ill patients.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) incidence is used as a quality
      measure. We hypothesized that patient and provider factors accounted for the
      higher incidence of VAP in trauma patients compared with other critically ill
      patients. METHODS: We conducted a 2-year study of all intubated adult patients at
      our Trauma Center. VAP was identified according to the Centers for Disease
      Control and Prevention definition. Groups were compared for the incidence of VAP
      and outcomes. RESULTS: The cohort of 2,591 patients included 511 trauma patients
      and 2,080 nontrauma patients. VAP occurred in 161 patients and more frequently in
      trauma patients (17.8% vs. 3.4%, p < 0.001). The overall death rate (17.4% vs.
      9.8%, p < 0.001) and the death rate for VAP patients (31.4% vs. 11%, p = 0.002)
      was higher in the nontrauma group. Bronchoalveolar lavage was performed more
      frequently in the trauma patient group (22.1% vs. 8.9%, p < 0.001), and gram
      negative organisms were isolated more commonly in trauma patients (65.9% vs. 30%,
      p < 0.001), respectively. VAP occurred earlier among the trauma group (mean 8.9
      days vs. 14.1 days, p < 0.001). Trauma represented an odds ratio of 3.9 (95%
      confidence interval 2.4-6.3, p < 0.001) for the development of VAP. CONCLUSION:
      The incidence of VAP is greatest among trauma patients at our institution. The
      increased use of bronchoalveolar lavage, the earlier onset of VAP, and the higher
      incidence of gram-negative pneumonias suggest that both patient and provider
      factors may influence this phenomenon. VAP was associated with increased
      mortality in the nontrauma group only. These factors should be considered before
      VAP is applied as a quality indicator.

PMID- 21068614
TI  - Family presence during trauma resuscitation: ready for primetime?
AB  - BACKGROUND: The concept of family presence during trauma resuscitation (FPTR)
      remains controversial. Healthcare providers have expressed concern that
      resuscitation of severely injured trauma patients is inappropriate for family
      members as they may have psychologic distress, disrupt resuscitative efforts, or
      misinterpret provider actions, which can ultimately impact satisfaction with
      care. The minimal evidence that exists is descriptive or anecdotal. METHODS:
      Using a previously developed FPTR protocol, a prospective, comparative study
      assessing 50 adult family members, who were present (n = 25) or not present (n =
      25) with their severely injured adult family member during resuscitation, was
      conducted. Family member anxiety was assessed using State-Trait Anxiety
      Inventory, satisfaction using a Revised-Critical Care Family Needs Inventory, and
      well-being using Family Member Well-being Index within 48 hours of intensive care
      unit admission. Mean total scores were compared for both groups with independent
      t tests. Significance was set at p < 0.05. RESULTS: Age and Injury Severity Score
      were statistically equivalent in all patients. Anxiety, satisfaction, and well
      being were not statistically different in family members present compared with
      those not present during resuscitation. There were no untoward events during
      resuscitation efforts. Family members present felt they benefited the patient and
      gained a better understanding of the situation. Conversely, family members not
      present commented that they would have preferred to have been present during
      resuscitation. CONCLUSIONS: Family members present during trauma resuscitation
      suffered no ill psychologic effects and scored equivalent to those family members
      who were not present on anxiety, satisfaction, and well-being measures. Quality
      of care during trauma resuscitation was maintained. The fact that all the family
      members would repeat experience again supports the idea that FPTR was not too
      traumatic for those who chose to be present.

PMID- 21068615
TI  - An evidence-based review: helmet efficacy to reduce head injury and mortality in
      motorcycle crashes: EAST practice management guidelines.

PMID- 21068616
TI  - Bicycle commuter injury prevention: it is time to focus on the environment.
AB  - BACKGROUND: Few data exist on the risk of injury while commuting to work or
      school by bicycle. The proportion of commuters choosing to travel by bike is
      increasing in the United States, and information on injury incidence and the
      influences of rider characteristics and environmental factors may suggest
      opportunities for prevention actions. METHODS: Bicycle commuters in the Portland,
      OR, metropolitan area were recruited via the websites and community advertising
      to participate in a 1-year study. Riders completed an initial online survey along
      with 12 monthly surveys describing their commutes and injury events from
      September 2007 to August 2008. A traumatic event was considered a serious
      traumatic event if medical attention was sought. RESULTS: Nine hundred sixty-two
      adult bicyclists (52% men and 48% women) with a mean age of 36.7 +/- 0.4 years
      (range, 22-70 years) commuted an average of 135 miles (range, 7-617) per month.
      There were 225 (23%) beginner, 256 (27%) intermediate, and 481 (50%) advanced
      riders. Four hundred twenty (44%) had a prior traumatic event. Over the 1-year
      period, 164 (18%) riders reported 192 traumatic events and 49 (5%) reported 50
      serious traumatic events. The incidence rates of traumatic events and serious
      traumatic events were 15.0 (95% CI, 13.2-17.5) and 3.9 (95% CI, 2.9-5.1) per
      100,000 miles commuted. There were no differences in age, gender, safety
      practices, and experience levels between commuters who experienced a traumatic
      event and those who did not. CONCLUSIONS: Approximately 20% of bicycle commuters
      experienced a traumatic event and 5% required medical attention during 1 year of
      commuting. Traumatic events were not related to rider demographics, safety
      practices, or experience levels. These results imply that injury prevention
      should focus on improving the safety of the bicycle commuting environment.

PMID- 21068617
TI  - Preservation of splenic immunocompetence after splenic artery angioembolization
      for blunt splenic injury.
AB  - BACKGROUND: Splenic artery angioembolization (SAE) is increasingly being used as
      an adjunct to nonoperative management for stable patients with blunt splenic
      injury (BSI). However, little is known about splenic immunocompetence after SAE.
      This study aims at assessing splenic immunocompetence after SAE for BSI. METHODS:
      Peripheral blood was obtained from BSI patients (n = 8) who had SAE >6 months
      prior. Splenic immunocompetence was assessed by isolating mononuclear cells and
      incubating with CD4 and CD45RA and CD45RO antibody to analyze the proportion of T
      cells expressing CD4 receptor, or coexpressing CD4 and either CD45RA or CD45RO
      receptors. Cells were counted by fluorescence-activated cell sorting and compared
      with trauma patients that had splenectomy for BSI also >6 months prior (n = 4,
      negative controls) and normal healthy volunteers with intact spleens (n = 4,
      positive controls). RESULTS: The test was discriminatory for the asplenic state.
      %CD4 cells were significantly lower in splenectomized patients (16 +/- 1) versus
      normal (40 +/- 2), p < 0.05. This was due to significant decrease (8 +/- 2 vs. 26
      +/- 4, p < 0.05) in %CD4CD45RA cells whereas the proportion of CD4CD45RO cells
      were maintained similar to normal. SAE patients had values (CD4, 36 +/- 2, and
      CD4CD45RA, 24 +/- 2) comparable to normal (p > 0.05) and significantly higher
      than splenectomized patients (p < 0.05). When the SAE group was subdivided into
      main (total, n = 4) and branch vessel (partial, n = 4) SAE, results were the same
      for both types of SAE. CONCLUSION: Splenic immune function, measured by T-cell
      subset, generated only in the presence of an immunocompetent spleen, is preserved
      after SAE for BSI, main or partial.

PMID- 21068618
TI  - Application of a trauma intensivist model to a Level II community hospital trauma
      program improves intensive care unit throughput.
AB  - BACKGROUND: Critical care-trained trauma surgeons are the ideal care provider for
      severely injured patients. This "captain of the ship" (COS) assumes complete
      responsibility of the patient, from initial resuscitation to eventual discharge.
      Unlike American College of Surgeons-verified Level I centers, many nonacademic,
      community hospital trauma centers use a more fragmented approach, with care in
      the intensive care unit (ICU) delegated to a committee of multiple specialists.
      We hypothesized that dedicated trauma intensivists as COS in a community hospital
      could improve ICU outcome. METHOD: Beginning from September 2005, dedicated full
      time trauma intensivists, without any resident coverage, assumed primary
      responsibility of all trauma patients admitted to a Level II Pennsylvania state
      verified trauma center. The ICU care was uninterrupted 24 hours a day, 365 days a
      year. Subspecialty consultations, for recommendations in care only, were
      selectively obtained as clinically indicated. We compared the 3 years before the
      implementation of the COS model (PRE: 2003-2005) with the 3 years after the model
      (POST: 2006-2008). A p-value <= 0.05 was considered significant. RESULTS: There
      were equal numbers of patients admitted to the ICU setting in both the periods.
      In the PRE and POST periods, both age (46.9 years vs. 52.4 years; p < 0.001) and
      Injury Severity Score (16.1 vs. 16.7; p = 0.01) were of significance. We observed
      significant differences in ventilator days (mean, 8 days vs. 6 days; p = 0.002)
      and mean ICU days (4.9 days vs. 4.4 days; p < 0.001) across the study periods.
      Days to tracheostomy also achieved statistical significance (9.1 vs. 8.1; p =
      0.03). The number of medical consults decreased by 19% in the POST group (p <
      0.001). Hospital stay days were not statistically different (7.4 vs. 7.2; p =
      0.18). After adjusting for higher age and Injury Severity Score in the POST
      period, we noted no difference in the expected mortality rate. CONCLUSION: A
      trauma intensivist-driven model can be successfully adopted in a nonacademic
      community trauma program, without the need for a residency program. A
      decentralized ICU care model produces inefficiencies, diminishes the role of the
      trauma service, and decreases the overall throughput of trauma patients.

PMID- 21068619
TI  - Emergency medical services transport decisions in posttraumatic circulatory
      arrest: are national practices congruent?
AB  - OBJECTIVE: To catalog the 9-1-1 emergency medical services (EMS) transport
      practices for posttraumatic circulatory arrest patients (PTCAPs) in the majority
      of the nation's largest municipalities and to compare those practices to
      guidelines recommended by the National Association of EMS Physicians (NAEMSP) and
      American College of Surgeons Committee on Trauma (ACSCOT). METHODS: A survey was
      conducted in 33 of the nation's largest cities primarily to determine whether or
      not individual EMS systems transport PTCAPs to hospitals and, if so, whether or
      not the initial electrocardiographic (ECG) rhythm or mechanism of injury affected
      those transport decisions. RESULTS: All 33 cities (100%) responded. Seven (21%)
      indicated that EMS would transport an "asystolic blunt trauma patient" emergently
      or "leave the transport decision to paramedic judgment" despite NAEMSP-ACSCOT
      guidelines to terminate resuscitation in such cases. Likewise, 15 (46%) of the 33
      EMS agencies would transport "asystolic penetrating trauma patients" emergently.
      Similarly, 27 (82%) would transport penetrating injury patients and 20 (61%)
      would transport blunt trauma patients with persistent ECG activity but no
      palpable pulses. However, only five systems had policies that included a minimum
      ECG heart rate criterion for transport, and all agencies that monitor ECG (n =
      32) would transport PTCAPs found with ventricular fibrillation. CONCLUSIONS: Many
      of the nation's highest volume EMS systems transport certain PTCAPs emergently,
      contrary to NAEMSP-ACSCOT guidelines to terminate resuscitative efforts in such
      cases. Reasons for these discrepancies should be evaluated to help better
      delineate applicable consensus guidelines for large urban EMS agencies.

PMID- 21068621
TI  - Variable application and misapplication of cricoid pressure.
AB  - BACKGROUND: In 1961, Sellick described a three-finger technique of cricoid
      pressure used to prevent gastric regurgitation during induction of anesthesia.
      The "Sellick maneuver" is now used worldwide. The authors have observed great
      variability in the application of cricoid pressure by health care providers and
      have suspected that misapplication occurs. The objectives of this observational
      study were to determine how many different techniques of cricoid pressure were
      being used and to identify the reasons for such variability of technique.
      METHODS: During a 30-month period, the authors observed 32 health care providers
      applying cricoid pressure at five hospitals. The technique and the professional
      degree of the person performing the maneuver were recorded. We also reviewed five
      national courses that provide airway management training to determine which
      technique of cricoid pressure was being taught. RESULTS: Ten different techniques
      of cricoid pressure were identified in 32 observations. We identified cases in
      which pressure was mistakenly applied to the thyroid cartilage and
      sternocleidomastoid muscles. The original three-finger Sellick technique was
      rarely used (3 of 32). A review of five national training courses revealed that
      none provide specific cricoid pressure training. CONCLUSION: This observational
      study demonstrates that there is great variability in the application of cricoid
      pressure, identifying 10 different techniques in 32 observations. Misapplication
      does occur with possible patient harm. We suggest four possible reasons for this
      variability of technique. The authors use the three-finger cricoid pressure
      technique as originally described by Sellick and thought that this technique is
      effective, easy to teach, and safely keeps the fingers in the midline of the
      cricoid cartilage.

PMID- 21068620
TI  - Influence of alcohol on early Glasgow Coma Scale in head-injured patients.
AB  - BACKGROUND: To assess the depressant effects of alcohol on the level of
      consciousness of patients admitted with head injuries, this study examined the
      changes that occur in the Glasgow Coma Scale (GCS) of traumatic brain injury
      patients over time. METHODS: The records of 269 head trauma patients
      consecutively admitted to the neurosurgery intensive care unit were examined
      retrospectively. Eighty-one patients were excluded because of incomplete data.
      The remaining 188 patients were further divided into an intoxicated group (blood
      alcohol concentration [BAC] >= 0.08%, n = 100 [53%]) and a nonintoxicated group
      (BAC <0.08%, n = 88 [47%]). The GCS in the prehospital setting, in the emergency
      department, and the highest GCS achieved during the first 24 hours postinjury
      were compared. RESULTS: The change between emergency department-GCS and the best
      day 1 GCS in the intoxicated group was greater than the nonintoxicated group and
      deemed clinically and statistically significant; median change (3 vs. 0) p <
      0.001. To assess whether these results were directly related to the BAC%,
      piecewise regression using a general linear model was used to assess the
      intercept and slope of alcohol on the changes of GCS with cutting point at BAC% =
      0.08. The analysis showed that, in the nonintoxicated range, the effect of
      alcohol was not significantly related to the changes of GCS. But in the
      intoxicated range, BAC% was significantly positively related to the changes of
      GCS. CONCLUSION: This study concludes that the GCS increases significantly over
      time in alcohol intoxicated patients with traumatic brain injury.

PMID- 21068622
TI  - Platelet aggregation inhibitors, platelet function testing, and blood loss in hip
      fracture surgery.
AB  - BACKGROUND: The purpose of our prospective study was to analyze how many patients
      with hip fractures are on treatment with platelet aggregation inhibitors (aspirin
      and clopidogrel), how many of these patients have impaired platelet function as
      measured by the PFA-100, and whether there is an association between
      perioperative blood loss and either intake of platelet inhibitors or platelet
      function. METHODS: Four hundred sixty-two patients with hip fractures were
      investigated. Surgery (most commonly dynamic screw fixation and hemiarthroplasty)
      was performed on day 1.3 (in patients on clopidogrel on day 3). Platelet function
      analysis was performed with the PFA-100, using the collagen and epinephrine
      closure time. Transfusion requirement and drain blood loss were measured.
      RESULTS: Ninety-eight patients (21%) were on treatment with aspirin, of those, 64
      patients (65%) had impaired platelet function. Twenty-two patients (5%) were on
      clopidogrel, of those, 15 patients (68%) had impaired platelet function. Of the
      patients without platelet aggregation inhibitors, 29% had impaired platelet
      function. Mortality, major bleeding, red blood cell requirement, and drainage
      blood loss did not correlate with platelet aggregation inhibitor intake or
      platelet function. CONCLUSIONS: It is not possible to predict the platelet
      function by asking patients about intake of aspirin or clopidogrel. Perioperative
      blood loss did not correlate with either history of platelet aggregation
      inhibitor intake or platelet function as determined by PFA-100. Therefore, the
      measurement of platelet function is of little clinical relevance in patients with
      hip fractures. In patients treated with aspirin, surgery should not be delayed,
      and patients on clopidogrel can be operated on 3 days after stopping the drug
      without increased bleeding risk.

PMID- 21068623
TI  - Sacroiliac joint fusion with fibular bone graft in patients with failed
      percutaneous iliosacral screw fixation.
AB  - BACKGROUND: Numerous studies have described screw fixation of sacroiliac (SI)
      joint, but there have been very few reports in the literature regarding long-term
      pain levels after SI joint fixation and their management. The objective of this
      study was to analyze the results of SI joint fusion with fibular bone graft in
      patients with persistent late pain after iliosacral screw fixation. METHODS:
      Eleven consecutive patients with persistent late pain following iliosacral screw
      fixation with failed conservative methods were managed with fibular bone grafting
      of the SI joint. The patients were followed up at 2, 6, 12, 24 weeks and every 3
      months thereafter. They were clinically assessed for pain, infection, and
      ambulation. RESULTS: The average duration of follow-up was 18 months. There were
      neither intraoperative complications nor postoperative wound infection. Eight
      patients were pain free and returned to their work. The remaining three patients
      were having persistent-localized pain, but they were able to manage their daily
      activities. CONCLUSIONS: Fibular graft is feasible and apparently effective
      choice for SI joint fusion. This procedure avoids further metal work, which
      results in successful fusion and pain relief as well as stabilizing the SI joint.

PMID- 21068624
TI  - Injury analyses in rural children: comparison of Old-Order Anabaptists and non
      Anabaptists.
AB  - BACKGROUND: Southwestern Ontario largely comprises rural farming districts and is
      home to numerous Old-Order Anabaptist settlements. Our objective was to describe
      the injuries sustained by rural children, both Old-Order Anabaptist and non
      Anabaptist, to better target injury prevention programs. METHODS: We
      retrospectively examined injury data of rural children in Southwestern Ontario
      with injury severity scores >= 12 obtained from hospital and trauma databases
      (1997-2007). RESULTS: A total of 422 rural children were included in this study:
      7.8% Anabaptist (n = 33) and 92.2% non-Anabaptist (n = 389). The age of injured
      Anabaptist children (median, 7 years; interquartile range = 10) was younger than
      non-Anabaptist children (median, 14 years; interquartile range = 7; p < 0.001).
      Anabaptist children were most frequently injured on their property (48.5%; n = 16
      of 33; p < 0.001). Non-Anabaptist children were mostly injured on roads (56.8%; n
      = 221 of 389; p < 0.05) and by motor vehicle collisions (MVCs; 40.1%; n = 156 of
      389; p = 0.02). Frequent causes of injury among Anabaptist children were falls
      (24.2%; n = 8 of 33; p = 0.02), animals (15.2%; n = 5 of 33; p = 0.004), and
      buggies (9.1%; n = 3 of 33). Approximately half of both groups injured in MVCs
      did not use seat belts. There were no significant differences between cohorts in
      sex, injury severity scores, hospitalization days, rates of complications,
      interventions, comorbidities, or mortality rates. CONCLUSIONS: Injuries to
      Anabaptist children occur at a young age, primarily on their property, and
      exhibit a unique spectrum of mechanisms. In contrast, injuries to non-Anabaptist
      children occur at an older age, primarily on roads, and in MVCs. The use of
      protective devices was low among all rural children. Development of collaborative
      injury prevention programs targeted to distinct rural communities, including
      Anabaptist and non-Anabaptist, are needed for reducing injuries among rural
      children.

PMID- 21068625
TI  - Urethrorectal fistula repair in children: urologic perspective.
AB  - OBJECTIVES: We report our experience in the management of urethrorectal fistulae
      in children with emphasis on the complexity of this rare disease. PATIENTS AND
      METHODS: A retrospective review was performed in cases that underwent repair of
      urethrorectal fistula at our center between 1997 and 2007. Records were reviewed
      for age, history, presentation, radiologic data, operative data, and condition at
      last follow-up. RESULTS: Five children were managed for urethrorectal fistula.
      Their mean age was 6.8 years (range, 2 months-12 years). One case had congenital
      urethrorectal fistula and four had acquired fistulas including two after abdomino
      perineal pull through for imperforate anus, one case post perineal urethroplasty,
      and another post repair of posttraumatic rectal tear. All patients presented with
      history of passing urine both through the rectum and the urethral meatus. We have
      three urinary diverted cases: one case in whom urinary and fecal diversions were
      performed and the remaining case was operated without diversion. Perineal
      approach was adopted in four procedures and abdomino-perineal approach in one.
      One patient required optical internal urethrotomy for anastomotic stricture at 6
      months follow-up. CONCLUSIONS: Urethrorectal fistula is a rare complication
      whether congenital or iatrogenic. Perineal repair is challenging, necessities
      meticulous dissection, adequate vascularity of the edges, and interposition of
      vascularized flaps and is potentially successful.

PMID- 21068626
TI  - Pediatric applied trauma research network: a call to action.
AB  - The Institute of Medicine and other national authorities have identified not only
      critical deficiencies in pediatric trauma care but also insufficient research to
      address these deficiencies. National research initiatives are needed to
      understand how best to treat, prevent, and rehabilitate seriously ill and injured
      children so that we can prioritize, support, and implement necessary changes.
      Yet, despite the enormity of this public health problem, there is no
      comprehensive national pediatric trauma research agenda and no infrastructure to
      support a pediatric trauma research network. The development of a research
      consortium such as a Pediatric Applied Trauma Research Network, is the next
      logical step to address these challenges.

PMID- 21068627
TI  - The image of trauma. Gastric transection from blunt abdominal trauma.

PMID- 21068629
TI  - Comments on comparison of tracheal intubation using Airway scope and Macintosh
      laryngoscope in patients with simulated limitation of neck movements.

PMID- 21068630
TI  - Application of D-dimer to predict adult traumatic brain injury.

PMID- 21068631
TI  - Comments and clarifications regarding "improved characterization of combat
      injury".

PMID- 21068633
TI  - Technology for you.

PMID- 21068634
TI  - Motor proficiency in children with neurofibromatosis type 1.
AB  - PURPOSE: Neurofibromatosis type 1 (NF1) is a genetic disorder with associated
      musculoskeletal abnormalities, tumors, and developmental delays. The purpose of
      this study was to investigate and characterize the motor proficiency of children
      with NF1. METHODS: Children with NF1 were assessed using the Bruininks-Oseretsky
      Test (BOT 2) instrument. The NF1 group scores were compared with age and sex
      matched test norms. RESULTS: Twenty-six children participated in the study. The
      NF1 group had statistically significant lower scores (P < .05) for the total
      motor composite (Z = -1.62) and 7 of the 8 subtests. Nineteen percent (n = 5)
      scored in the average category, 54% (n = 14) scored in the below-average
      category, and 27% (n = 7) scored in the well-below-average category. CONCLUSIONS:
      Children with NF1 have significantly lower motor proficiency than the BOT 2
      normative scores. The results indicate the BOT 2 is useful in identifying and
      characterizing delays in motor proficiency for children with NF1.

PMID- 21068635
TI  - The performance of children developing typically on the pediatric balance scale.
AB  - PURPOSE: To investigate Pediatric Balance Scale (PBS) performance in children
      developing typically. METHODS: The PBS was administered to 643 children
      developing typically per parent report, aged 2 years 4 months to 13 years 7
      months. RESULTS: A 2-way analysis of variance and post hoc analyses identified
      significant age and gender differences in PBS performance. The Spearman rank
      correlation analysis identified associations between PBS scores and age, height,
      weight, and body mass index. Data were analyzed using 95% confidence intervals of
      the means to identify PBS typical performance ranges for each age and gender
      group. The lower bound of the 95% confidence intervals was used to identify
      outliers and determine a "critical cut score" for each group. The numbers and
      percentages of children scoring above and below this critical cut score were
      calculated to further describe the sample. CONCLUSIONS: This study provides the
      clinician with guidelines for interpretation of PBS performance.

PMID- 21068636
TI  - Effectiveness of treadmill training in children with motor impairments: an
      overview of systematic reviews.
AB  - PURPOSE: The purpose of this review was to synthesize current evidence from
      systematic reviews on the effectiveness of treadmill training (TT), including
      partial body-weight support (PBWS) TT (PBWSTT), TT only, robotic-assist PBWSTT,
      and mixed TT, in children with motor impairments. METHODS: Systematic literature
      searches were conducted in 10 databases through May 2010. Two reviewers
      independently selected titles, abstracts (k = 0.78), and full-text articles (k =
      1.0). Of the 1166 titles retrieved, 5 studies met the inclusion criteria. Quality
      of included studies was assessed using AMSTAR criteria. RESULTS: Results of each
      systematic review were tabulated on the basis of levels of evidence, with
      outcomes categorized according to the International Classification of
      Functioning, Disability, and Health framework. Conflicting interpretations of
      outcomes were found between reviews, yet conclusions were similar. CONCLUSIONS:
      TT demonstrates encouraging results, but more rigorous research is needed before
      clinicians can be confident of its effectiveness and clinical guidelines can be
      developed.

PMID- 21068637
TI  - A developmental perspective on congenital muscular torticollis: a critical
      appraisal of the evidence.
AB  - PURPOSE: The aims of this review were to (1) identify and evaluate research
      evidence regarding the developmental outcomes of infants with congenital muscular
      torticollis (CMT) and (2) critically appraise and compare the outcomes of
      interventions targeting neck muscle extensibility and strength with those
      considering neck muscle function within the broader context of global infant
      development. SUMMARY: An association between CMT and early developmental delay is
      supported by levels 3B, 4, and 5 evidence; no evidence was found of longer-term
      influences of CMT on the development of perceptual, cognitive, and motor skills.
      The effectiveness of passive manual stretching is supported by levels 2A, 3B, 4,
      and 5 evidence; no clear evidence was found of the effectiveness of
      developmentally supportive interventions. CONCLUSION: Controlled studies are
      needed to clarify the developmental consequences of CMT.

PMID- 21068638
TI  - Reaching and grasping a moving target is impaired in children with developmental
      coordination disorder.
AB  - PURPOSE: To investigate the performance of reaching and grasping a moving target
      in children with developmental coordination disorder (DCD). METHODS: Sixteen
      children with DCD and 11 age-matched controls were instructed to reach and grasp
      a toy car that was sliding down an 8 degrees  or 15 degrees  slope. Reaction time
      (RT), movement time (MT), and peak force (PF) were recorded. RESULTS: Children
      with DCD failed 35% of total test trials. Within the successful trials, children
      with DCD had significantly longer RTs and MTs and generated larger PF than
      control children (P < .05). When the slope increased from 8 degrees  to 15
      degrees , both groups of children could adjust MT and PF (P < .01). CONCLUSION:
      Children with DCD were slower and generated larger force to reach and grasp a
      moving target than their age-matched peers. However, the ability to modify the MT
      and grip force appeared to be preserved in children with DCD.

PMID- 21068639
TI  - Use of diagnosis and prognosis by pediatric physical therapists.
AB  - PURPOSE: Diagnosis and prognosis are components of the Patient Client Management
      Model of the Guide to Physical Therapist Practice. The purpose of this study is
      to determine how pediatric physical therapists (PPTs) define and use diagnosis
      and prognosis in their practice. SUBJECTS AND METHODS: This article reports the
      themes revealed in answers to open-ended questions on diagnosis and prognosis (n
      = 7 to n = 68) in an electronic survey that was sent to PPTs who are members of
      the American Physical Therapy Association (APTA) Section on Pediatrics, and non
      Section members of the APTA who identify themselves as PPTs. RESULTS: In this
      sample, PPTs lack consistency in their definition and use of the terms diagnosis
      and prognosis. Many respondents reported a level of discomfort with the
      relevance, utility, and usefulness of diagnosis and prognosis. CONCLUSION:
      Despite literature on diagnosis and prognosis, PPTs continue to struggle with
      using these concepts in their practice.

PMID- 21068640
TI  - Reliability of still photography measuring habitual head deviation from midline
      in infants with congenital muscular torticollis.
AB  - PURPOSE: To establish intrarater and interrater reliability of still photography
      for measuring habitual head deviation from midline in infants with congenital
      muscular torticollis (CMT). METHODS: Two investigators took still photographs of
      30 infants with CMT in a supine position and measured head deviation angles with
      a protractor. Data analysis included paired t tests, Pearson r, and intraclass
      correlation coefficients (ICC) with 95% confidence intervals. RESULTS: Pearson r
      varied from 0.80 to 0.85 for the same rater and from 0.72 to 0.99 for 2 different
      raters. The ICC (3,1) varied from 0.79 to 0.84, and ICC (2,1) varied from 0.72 to
      0.99. Participants with smaller head-tilt angles showed greater variability in
      head position. CONCLUSIONS: Still photography is a reliable method for measuring
      habitual head deviation from midline in infants with CMT. Several modifications
      to the measurement procedure have been suggested.

PMID- 21068641
TI  - Sharing of lessons learned from multisite research.
AB  - PURPOSE: To highlight key considerations for planning and implementing multisite
      research based on experiences and reflections in conducting a large,
      international, multisite study. DESCRIPTION: Successes and challenges encountered
      throughout a multisite study process, and collective recommendations for future
      researchers are presented. Considerations addressed include creation of the
      research team and a "community of practice," study preparation and management
      time, approval by institutional review boards, training of future researchers,
      recruitment and retention of participants, and dissemination and translation of
      study materials to consumers. IMPORTANCE TO MEMBERS: Multisite research has the
      potential to create knowledge for pediatric physical therapy through
      collaboration among knowledgeable researchers and expert practitioners and by
      increasing the potential for generalization of findings. Effective planning,
      including anticipation of challenges, is critical to a successful study. Our
      collective experiences may assist practitioners and researchers in planning,
      implementing, and completing future multisite studies.

PMID- 21068642
TI  - Effects of motor control intervention for children with idiopathic toe walking: a
      5-case series.
AB  - PURPOSE: To describe and evaluate the effects of motor control intervention in
      young children diagnosed with idiopathic toe walking. METHODS: Five children
      received motor control intervention in a multiple-case series design using a
      nonconcurrent, variable baseline. Multiple gait measures were taken before and
      during the intervention phase. Pre- and posttreatment measures of gross motor
      development and ankle dorsiflexion range of motion were compared. RESULTS: During
      the intervention phase, heel strike frequency showed an upward slope for 1
      participant, slight upward trends for 3 participants, and no change for 1
      participant. Parents indicated minimal gait change within the children's regular
      environments. Gross motor skill scores increased but were not statistically
      significant. Passive ankle range of motion improved and was maintained (P =
      .002). CONCLUSIONS: Presentation of children with idiopathic toe walking varies
      and refinement is needed for gait measures and assessment methods. Intervention
      improved ankle mobility, but additional components appear necessary to attain
      spontaneous heel-toe gait.

PMID- 21068643
TI  - Long-term physical therapy management following a single-event multiple level
      surgery.
AB  - PURPOSE: This case report provides an overview of surgical procedures, including
      single-event multiple level surgery (SEMLS) used in the management of secondary
      conditions in cerebral palsy (CP). Physical therapy (PT) management over 35
      months following SEMLS is described for an adolescent (Gross Motor Function
      Classification System level II) with CP. SUMMARY OF KEY POINTS: When conservative
      management is not sufficient to manage secondary complications, SEMLS, combined
      with PT and family support, may provide the foundation for greater functional
      improvement than surgical correction of a single impairment. The outcome measures
      used following SEMLS included the Gross Motor Function Measure-66, Activity Scale
      for Kidsperformance38, goniometry, manual muscle testing, and Numerical Pain
      Rating Scale. STATEMENT OF CONCLUSIONS: Preoperative functional level can be
      exceeded and sustained beyond 24 months following surgery. RECOMMENDATIONS FOR
      CLINICAL PRACTICE: Rehabilitation following a SEMLS requires teamwork and a long
      term commitment to maximize outcomes.

PMID- 21068644
TI  - Student experiences in the neonatal intensive care unit: addendum to neonatal
      physical therapy competencies and clinical training models.
AB  - PURPOSE: To describe the appropriate experience for entry-level physical
      therapist students in the neonatal intensive care unit (NICU). KEY POINTS: Care
      for infants in the NICU represents a subspecialty within pediatric physical
      therapy delivered in a very complex environment. Recommendations for designing
      student educational experiences related to the NICU are provided.
      CONCLUSIONS/PRACTICE IMPLICATIONS: Supervised observation is the appropriate
      level of NICU experience for physical therapy students. Observation in the NICU
      cannot be used to demonstrate entry-level clinical competency defined as managing
      100% patient caseload in the setting. Additional closely supervised experiences
      with older, less fragile infants and children in neonatal follow-up clinics and
      pediatric wards can provide opportunities for entry-level physical therapist
      students interested in pediatrics to participate in examination and intervention
      with young children.

PMID- 21068645
TI  - Developmental pharmacogenetics of immunosuppressants in pediatric organ
      transplantation.
AB  - Cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil are the primary
      immunosuppressants used on pediatric organ transplantation. Therapeutic drug
      monitoring is used in daily practice, because their clinical use is hampered by a
      narrow therapeutic index and large variability. Tailoring immunosuppressive
      therapy to the individual patient to optimize efficacy and minimize toxicity is
      therefore essential. Because research in pharmacogenetics already identified
      polymorphisms impacting their pharmacokinetic parameters in adults, developmental
      pharmacogenetics of immunosuppressants holds promises for optimizing dosage
      regimens and improving clinical outcome in children. In this review, we focus on
      the impact of age and pharmacogenetics on these immunosuppressants in children
      undergoing organ transplantation.

PMID- 21068646
TI  - Population pharmacokinetic study of cyclosporine based on NONMEM in Chinese liver
      transplant recipients.
AB  - A population pharmacokinetic study of cyclosporine (CsA) was performed in liver
      transplant recipients. A total of 3731 retrospective drug monitoring data points
      at predose (C0) and 2 hours postdose (C2) were collected from 124 liver
      transplant recipients receiving CsA microemulsion. Population pharmacokinetic
      analysis was performed using the program NONMEM (nonlinear mixed-effect
      modeling). Various covariates potentially related to CsA pharmacokinetics were
      explored, and the final model was validated by a bootstrap method and by
      assessing the predictive performance using empiric Bayesian estimates. A one
      compartment model with first-order absorption was considered. Population
      parameters of apparent clearance (CL/F) and volume of distribution were estimated
      as 23.1 L/h and 105 L, respectively. CL/F was influenced by four covariates:
      duration of CsA therapy (DT), hematocrit (HCT), and concurrent prednisone dose
      (PR). The final model for CL/F was fitted as follows: CL/F = 23.1 + 0.5 *
      (DT/200) - 0.07 * HCT + 0.04 * PR. The interindividual variability in CL/F,
      volume of distribution, and Ka calculated as coefficient of variation were 15.1%,
      9.3%, and 66.0%, respectively. The intraindividual variability was 18.6%. The
      model fitted well with the observed data, and the bootstrap method guaranteed
      robustness of the population pharmacokinetic study model. Model validation was
      performed by a visual predictive check. Moreover, simulation was conducted to
      facilitate the individualized treatment based on patient information and the
      final model. The model to characterize population pharmacokinetic study of CsA
      provided better clinical individualization of CsA dosing in liver transplant
      recipients based on patient information and to assess patients' suitability for
      CsA therapy.

PMID- 21068647
TI  - Evaluation of limited sampling strategies for mycophenolic acid after
      mycophenolate mofetil intake in adult kidney transplant recipients.
AB  - Multiple limited sampling strategies (LSSs) have been proposed for estimation of
      mycophenolic acid (MPA) area under the concentration-time curve from 0 to 12
      hours postdose (AUC 0-12) after mycophenolate mofetil intake. The aim of this
      study was to provide summary information on all published LSSs for MPA and to
      evaluate their predictive performance in an independent population of kidney
      transplant recipients. Seventy-eight LSSs for MPA were identified. Sixty-nine
      full AUC profiles were collected from 45 subjects (25 cotreated with cyclosporine
      and 20 with tacrolimus). Predicted MPA AUC 0-12, calculated by applying the
      relevant concentration measurements within the LSS equations, was compared with
      full AUC calculated by using all concentration measurements in the linear
      trapezoidal rule. Four error indices (median prediction error, median percentage
      prediction error [MPPE], root median squared prediction error, and median
      absolute percentage prediction error [MAPE]) were used to evaluate bias and
      imprecision. Twelve of the 25 LSSs for cyclosporine-cotreated recipients and one
      of the 53 LSSs for tacrolimus-cotreated recipients displayed acceptable (less
      than 15%) bias and imprecision. In the cyclosporine group, two equations
      demonstrated the highest predictive power, one that used four time points in the
      first 6 hours postdose (r2 = 0.84, MPPE 1.6%, MAPE 7.8%) and one that used four
      time points in the first 4 hours postdose (r2 = 0.76, MPPE -0.8%, MAPE 10.2%). In
      the tacrolimus group, an equation that used two time points in the first 4 hours
      postdose was superior (r2 = 0.80, MPPE -3.0%, MAPE 13.6%). Application of the
      LSSs most appropriate for cyclosporine-cotreated patients to the tacrolimus
      cotreated group resulted in clinically unacceptable bias and imprecision and vice
      versa. High variability in performance of LSSs highlights the importance of
      validating any LSS before applying it to an alternative population. Attention to
      comedication use is of particular relevance when choosing a LSS.

PMID- 21068648
TI  - Effect of cyamemazine on the steady-state plasma concentrations of risperidone
      and 9-hydroxyrisperidone: a preliminary retrospective study.
AB  - Administration of cyamemazine, an antipsychotic drug with anxiolytic properties,
      together with other antipsychotic agents is common in patients with
      schizophrenia. This retrospective study investigated the effects of cyamemazine
      on the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone
      in 47 patients treated with 1 to 12 mg/day of risperidone. Of these 47 patients,
      24 were receiving cyamemazine comedication ("cyamemazine" group) and 23 patients
      were treated with risperidone alone ("control" group). Plasma concentrations were
      measured using a high-performance liquid chromatographic method with photodiode
      array ultraviolet detection. The median plasma concentration of risperidone was
      significantly higher in the cyamemazine group (31.5 ng/mL) than in the control
      group (5.0 ng/mL), whereas the 9-hydroxyrisperidone median concentration was
      significantly lower in the cyamemazine group (16.5 ng/mL versus 39.0 ng/mL in the
      control group). However, the sum of risperidone plus 9-hydroxyrisperidone (active
      moiety) plasma concentration was not significantly affected by cyamemazine
      comedication. A combination with cyamemazine resulted in an inverted metabolic
      ratio (risperidone/9-hydroxyrisperidone). These findings suggest that cyamemazine
      inhibits the 9-hydroxylation of risperidone and is probably an inhibitor of
      cytochrome P450 2D6 as are many other phenothiazine drugs.

PMID- 21068649
TI  - Influence of CYP2C9 genetic polymorphism and undernourishment on plasma-free
      phenytoin concentrations in epileptic patients.
AB  - The objective of this study was to study the effect of CYP2C9 genetic
      polymorphism and undernourishment on free phenytoin concentrations in epileptic
      patients. The study was done in 70 patients who were taking phenytoin therapy for
      the treatment of epileptic seizures. Genotyping of CYP2C9 (*2 and *3) was
      determined by the polymerase chain reaction-restriction fragment length
      polymorphism method. Bound and free plasma phenytoin was separated using
      equilibrium dialysis technique. Total and free phenytoin concentrations were
      measured by the reverse-phase high-performance liquid chromatography method.
      Patients were broadly classified into well-nourished and undernourished and
      further subclassified by CYP2C9 genotypes. In well-nourished groups (G1 to G3
      group), free phenytoin concentrations were significantly higher in the
      heterozygous poor metabolizer of CYP2C9 genotype (G2) group (3.1 +/- 0.62 MUg/mL)
      and homozygous poor metabolizer of CYP2C9 genotype (G3) group (4.3 +/- 1.76
      MUg/mL) when compared with patients with the wild-type CYP2C9 (G1) group (1.1 +/-
      0.72 MUg/mL). Similarly, in undernourished patient groups (G4-G6 group), free
      phenytoin concentrations were significantly higher in the wild-type CYP2C9 (G4)
      group (2.5 +/- 0.52 MUg/mL), heterozygous poor metabolizer of CYP2C9 genotype
      (G5) group (4.3 +/- 1.76 MUg/mL), and homozygous poor metabolizer of CYP2C9
      genotype (G6) group (8.2 +/- 1.08 MUg/mL) when compared with well-nourished
      patients with the wild-type CYP2C9 (G1) group (1.1 +/- 0.72 MUg/mL). The
      percentage increase in free phenytoin concentration by undernourishment, CYP2C9
      allelic variants, and undernourishment cum CYP2C9 allelic variants were 127%,
      290%, and 472%, respectively, compared with well-nourished patients with the wild
      type CYP2C9 genotype (G1) group. The contribution of undernourishment and genetic
      factors (CYP2C9 allelic variant) for developing phenytoin toxicity was calculated
      to have an odds ratio of 37.3 (P < 0.0001). Undernourishment and variant CYP2C9
      alleles elevate free phenytoin concentrations individually and in combination
      show additive effects.

PMID- 21068651
TI  - Falsely elevated whole blood cyclosporine concentrations measured by an
      immunoassay with automated pretreatment.

PMID- 21068650
TI  - The effect of coadministration of duloxetine on steady-state serum concentration
      of risperidone and aripiprazole: a study based on therapeutic drug monitoring
      data.
AB  - Previous studies have categorized duloxetine as a moderate inhibitor of CYP2D6.
      The aim of the present study was to investigate the potential interactions
      between duloxetine and the two CYP2D6 substrates risperidone and aripiprazole in
      psychiatric patients. Serum concentration data from patients treated with
      risperidone (n = 8) or aripiprazole (n = 7) in combination with duloxetine were
      retrieved from therapeutic drug monitoring files at the Center for
      Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The degree of
      interaction was assessed by comparing the data with a control group of CYP2D6
      genotyped patients (homozygous "extensive metabolizers") using oral risperidone
      or aripiprazole without duloxetine. Coadministration of duloxetine did not
      significantly increase the concentration of the parent drug or the parent
      drug/metabolite ratio of either risperidone or aripiprazole. The present study
      therefore indicates that duloxetine may safely be used concomitantly with
      risperidone or aripiprazole.

PMID- 21068652
TI  - Lidocaine: the origin of a modern local anesthetic. 1949.

PMID- 21068653
TI  - Methicillin-resistant Staphylococcus aureus colonization, its relationship to
      nosocomial infection, and efficacy of control methods.

PMID- 21068654
TI  - Identification of the epidural space with optical spectroscopy: an in vivo swine
      study.
AB  - BACKGROUND: Accurate identification of the epidural space is critical for safe
      and effective epidural anesthesia or treatment of acute lumbar radicular pain
      with epidural steroid injections. The loss-of-resistance technique is commonly
      used, but it is known to be unreliable. Even when it is performed in conjunction
      with two-dimensional fluoroscopic guidance, determining when the needle tip
      enters the epidural space can be challenging. In this swine study, we
      investigated whether the epidural space can be identified with optical
      spectroscopy, using a custom needle with optical fibers integrated into the
      cannula. METHODS: Insertion of the needle tip into the epidural space was
      performed with midline and paramedian approaches in a swine. In each insertion,
      optical spectra were acquired at different insertion depths, and anatomical
      localization of the needle was determined by three-dimensional imaging with
      rotational C-arm computed tomography. Optical spectra that included both visible
      and near-infrared wavelength ranges were processed to derive estimates of the
      blood and lipid volume fractions. RESULTS: In all insertions, the transition of
      the needle tip to the epidural space from an adjacent tissue structure
      (interspinous ligament or the ligamentum flavum) was found to be associated with
      an increase in the lipid volume fraction. These increases, which ranged from 1.6-
      to 3.0-fold, were statistically significant (P = 0.0020). Lipid fractions
      obtained from the epidural space were 1.9- to 20-fold higher than those obtained
      from muscle (P = 0.0013). Accidental penetration of an epidural vein during one
      insertion coincided with a high blood volume fraction. CONCLUSIONS: The
      spectroscopic information obtained with the optical spinal needle is
      complementary to fluoroscopic images, and it could potentially allow for reliable
      identification of the epidural space during needle placement.

PMID- 21068655
TI  - Is routine use of a face mask necessary in the operating room?

PMID- 21068656
TI  - Positive end-expiratory pressure redistributes regional blood flow and
      ventilation differently in supine and prone humans.
AB  - BACKGROUND: Animal studies have demonstrated an interaction between posture and
      the effect of positive end-expiratory pressure (PEEP) on regional ventilation and
      lung blood flow. The aim of this study was to explore this interaction in humans.
      METHODS: Regional lung blood flow and ventilation were compared between
      mechanical ventilation with and without PEEP in the supine and prone postures.
      Six normal subjects were studied in each posture. Regional lung blood flow was
      marked with In-labeled macroaggregates and ventilation with Technegas (Tc).
      Radiotracer distributions were mapped using quantitative single-photon emission
      computed tomography. RESULTS: In supine subjects, PEEP caused a similar
      redistribution of both ventilation and blood flow toward dependent (dorsal) lung
      regions, resulting in little change in the V/Q correlation. In contrast, in prone
      subjects, the redistribution toward dependent (ventral) regions was much greater
      for blood flow than for ventilation, causing increased V/Q mismatch. Without
      PEEP, the vertical ventilation-to-perfusion gradient was less in prone postures
      than in supine, but with PEEP, the gradient was similar. CONCLUSIONS: During
      mechanical ventilation of healthy volunteers, the addition of PEEP, 10 cm H2O,
      causes redistribution of both lung blood flow and ventilation, and the effect is
      different between the supine and prone postures. Our results suggest that the
      addition of PEEP in prone might be less beneficial than in supine and that
      optimal use of the prone posture requires reevaluation of the applied PEEP.

PMID- 21068657
TI  - Hypoxia induces late preconditioning in the rat heart in vivo.
AB  - BACKGROUND: Although hypoxic late preconditioning (LPC) limits ischemia
      reperfusion injury in vitro, its cardioprotective effect is not established in
      vivo. METHODS: In part 1, rats were exposed to 4 h of hypoxia (16%, 12%, 8%
      oxygen) before 24 h of reoxygenation. In part 2, normoxic rats received early
      preconditioning with sevoflurane (1 minimum alveolar concentration [MAC] for 3 *
      5 min), continuous administration of 1 MAC sevoflurane, or 11 mg . kg . h
      propofol. Thereafter, all rats underwent 25 min of regional myocardial ischemia
      and 120 min of reperfusion. After reperfusion, hearts were excised for infarct
      staining. The expression of protein kinase C (PKC)alpha and PKCepsilon was
      assessed by Western blot analysis and the expression of heme oxygenase-1 and
      vascular endothelial growth factor by reverse transcriptase polymerase chain
      reaction. RESULTS: In normoxic control rats, infarct size was 62 +/- 6% of the
      area at risk. Hypoxic LPC reduced infarct size (LPC16: 36 +/- 11%, LPC12: 38 +/-
      10%, LPC8: 39 +/- 11%; each P < 0.001) to approximately the same magnitude as
      sevoflurane-preconditioning (40 +/- 8%; P < 0.001). Combined LPC16 and
      sevoflurane preconditioning was not superior to either substance alone.
      Continuous sevoflurane or propofol was not protective. The PKC inhibitor
      calphostin C abolished the cardioprotective effects of LPC16. PKCepsilon, but not
      PKCalpha, expression was increased 6 and 28 h after hypoxic LPC. Heme oxygenase-1
      and vascular endothelial growth factor were transiently up-regulated after 6 h.
      CONCLUSION: Hypoxic LPC at 8%, 12%, and 16% oxygen reduces infarct size in the
      rat heart in vivo. This effect is as powerful as sevoflurane-preconditioning.
      PKCepsilon is a key player in mediating hypoxic LPC.

PMID- 21068658
TI  - Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal
      column and dorsal roots attenuates dorsal horn neuronal excitability in
      neuropathic rats.
AB  - BACKGROUND: The sites of action and cellular mechanisms by which spinal cord
      stimulation reduces neuropathic pain remain unclear. METHODS: We examined the
      effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of
      the dorsal column and lumbar dorsal roots on the response properties of spinal
      wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury. The
      conditioning stimulation intensity was set at the lowest current that evoked a
      peak antidromic sciatic Aalpha/beta-compound action potential without inducing an
      Adelta- or C-compound action potential. RESULTS: Within 15 min of the dorsal
      column or root conditioning stimulation, the spontaneous activity rate of WDR
      neurons was significantly reduced in nerve-injured rats. Conditioning stimulation
      also significantly attenuated WDR neuronal responses to mechanical stimuli in
      nerve-injured rats and inhibited the C-component of the neuronal response to
      graded intracutaneous electrical stimuli applied to the receptive field in nerve
      injured and sham-operated rats. It is noteworthy that dorsal column stimulation
      blocked windup of WDR neuronal response to repetitive intracutaneous electrical
      stimulation (0.5 Hz) in nerve-injured and sham-operated rats, whereas dorsal root
      stimulation inhibited windup only in sham-operated rats. Therefore, stimulation
      of putative spinal substrates at A-fiber intensities with parameters similar to
      those used by patients with spinal cord stimulators attenuated established WDR
      neuronal hyperexcitability in the neuropathic condition and counteracted activity
      dependent increase in neuronal excitability (i.e., windup). CONCLUSIONS: These
      results suggest a potential cellular mechanism underlying spinal cord stimulation
      induced pain relief. This in vivo model allows the neurophysiologic basis for
      spinal cord stimulation-induced analgesia to be studied.

PMID- 21068659
TI  - Impact of a comprehensive safety initiative on patient-controlled analgesia
      errors.
AB  - BACKGROUND: Adverse drug events related to patient-controlled analgesia (PCA)
      place patients at risk. METHODS: We reviewed all critical incident reports at
      three tertiary care hospitals dated January 1, 2002, to February 28, 2009. In
      this longitudinal cohort study, critical incidents attributable to PCA errors
      were identified, and each incident was investigated. A safety intervention was
      implemented in February 2006 and involved new PCA pumps, new preprinted physician
      orders, nursing and patient education, a manual independent double-check, and a
      formal nursing transfer of accountability. RESULTS: A total of 25,198 patients
      were treated with PCA during this study, and 62 errors were found (0.25%), with
      21 (0.08%) involving pump programming. All errors occurred before the safety
      interventions were put in place. Compared with the preintervention period, the
      odds ratio of a PCA error postintervention was 0.28 (95% CI = 0.14, 0.53; P <
      0.001) whereas the odds ratio of a pump-programming error postintervention was
      0.05 (95% CI = 0.001, 0.30; P < 0.001). Programming the wrong drug concentration
      was the most common programming error (10 of 21). Improper setup of intravenous
      tubing was also common (8 of 62), with one incident leading to respiratory
      arrest. Most PCA errors resulted in no harm, but there was negative impact to
      patients 34% of the time. CONCLUSION: At less than 1%, the incidence of PCA
      errors is relatively low. Most errors occur during PCA administration. Safety can
      be improved by addressing equipment, education, and process issues.

PMID- 21068660
TI  - Intraoperative recruitment maneuver reverses detrimental pneumoperitoneum-induced
      respiratory effects in healthy weight and obese patients undergoing laparoscopy.
AB  - BACKGROUND: Pulmonary function is impaired during pneumoperitoneum mainly as a
      result of atelectasis formation. We studied the effects of 10 cm H2O of positive
      end-expiratory pressure (PEEP) and PEEP followed by a recruitment maneuver
      (PEEP+RM) on end-expiratory lung volume (EELV), oxygenation and respiratory
      mechanics in patients undergoing laparoscopic surgery. METHODS: Sixty consecutive
      adult patients (30 obese, 30 healthy weight) in reverse Trendelenburg position
      were prospectively studied. EELV, static elastance of the respiratory system,
      dead space, and gas exchange were measured before and after pneumoperitoneum
      insufflation with zero end-expiratory pressure, with PEEP alone, and with
      PEEP+RM. Results are presented as mean +/- SD. RESULTS: Pneumoperitoneum reduced
      EELV (healthy weight, 1195 +/- 405 vs. 1724 +/- 774 ml; obese, 751 +/- 258 vs.
      886 +/- 284 ml) and worsened static elastance and dead space in both groups (in
      all P < 0.01 vs. zero-end expiratory pressure before pneumoperitoneum) whereas
      oxygenation was unaffected. PEEP increased EELV (healthy weight, 570 ml, P <
      0.01; obese, 364 ml, P < 0.01) with no effect on oxygenation. Compared with PEEP
      alone, EELV and static elastance were further improved after RM in both groups (P
      < 0.05), as was oxygenation (P < 0.01). In all patients, RM-induced change in
      EELV was 16% (P = 0.04). These improvements were maintained 30 min after RM. RM
      induced changes in EELV correlated with change in oxygenation (r = 0.42, P <
      0.01). CONCLUSION: RM combined with 10 cm H2O of PEEP improved EELV, respiratory
      mechanics, and oxygenation during pneumoperitoneum whereas PEEP alone did not.

PMID- 21068661
TI  - Lipid emulsion reverses bupivacaine-induced asystole in isolated rat hearts:
      concentration-response and time-response relationships.
AB  - BACKGROUND: The concentration-response and time-response relationships of lipid
      emulsions used to reverse bupivacaine-induced asystole are poorly defined.
      METHODS: Concentration response across a range of lipid concentrations (0-16%) to
      reverse bupivacaine-induced asystole were observed using isolated rat heart
      Langendorff preparation. Cardiac function parameters were recorded during
      infusion. Concentrations of bupivacaine in myocardial tissue were measured by
      liquid chromatography and tandem mass spectrometry at the end of the experiment.
      RESULTS: Although all lipid-treated hearts recovered (cardiac recovery was
      defined as a rate-pressure product more than 10% baseline), no nonlipid-treated
      hearts (control group) did so. The ratio of the maximum rate pressure product
      during recovery to baseline value demonstrated a concentration-dependent
      relationship among lipid groups, with 0.25, 0.5, 1, 2, 4, 8, and 16%. Mean +/- SD
      values for each corresponding group were 22 +/- 4, 24 +/- 5, 29 +/- 6, 52 +/- 11,
      73 +/- 18, 119 +/- 22, and 112 +/- 10%, respectively (n = 6, P < 0.01). Rate
      pressure product in lipid groups with 4-16% concentrations was lower at 15-40 min
      than at 1 min, showing a decreasing tendency during recovery phase (P < 0.01).
      The concentration of myocardial bupivacaine in all lipid-treated groups was
      significantly lower than in the control group (P < 0.01). It was also lower in
      lipid groups with 2-16% concentrations than in those with concentrations at 0.25
      1% (P < 0.05), with the 16% group lower than groups with 2-8% concentrations (P <
      0.001). CONCLUSION: Lipid application in bupivacaine-induced asystole displays a
      concentration-dependent and time-response relationship in isolated rat hearts.

PMID- 21068662
TI  - Inhalation anesthesia increases V/Q regional heterogeneity during spontaneous
      breathing in healthy subjects.
AB  - BACKGROUND: The underlying mechanism for the increased alveolar-arterial oxygen
      tension difference resulting from almost all forms of general anesthesia is
      unknown. We hypothesized that inhalation anesthesia influences the intrapulmonary
      distribution of ventilation (V) and perfusion (Q), leading to less advantageous
      V/Q matching. METHODS: Ten healthy volunteers were studied in supine position on
      two separate occasions, once awake and once during mild anesthesia (sevoflurane
      inhalation) with maintained spontaneous breathing. On both occasions, the
      distribution of V and Q were simultaneously imaged using single photon emission
      computed tomography. V was tagged with [Tc]-labeled carbon particle aerosol and Q
      with [In]-labeled macroaggregates of human albumin. Atelectasis formation during
      anesthesia was prevented using low concentrations of oxygen in inhaled air.
      RESULTS: Mean V and Q distributions in the ventral-to-dorsal direction, measured
      in 20 equally spaced volumes of interest and in three regions of interest of
      equal volume, did not differ between conditions. Anesthesia, when compared with
      the awake state, significantly decreased the total heterogeneity of the Q
      distribution (P = 0.002, effect size 1.16) but did not alter V (P = 0.37, effect
      size 0.41). The corresponding V/Q total heterogeneity was higher under anesthesia
      (P = 0.002, effect size 2.64). Compared to the awake state, the V/Q frequency
      distribution under anesthesia became wider (P = 0.009, 1.76 effect size) with a
      tendency toward low V/Q ratios. CONCLUSION: Inhalation anesthesia alone affects Q
      but not V, suggesting that anesthesia has a direct effect on the active
      regulatory mechanism coordinating Q with V, leading to less favorable V/Q
      matching.

PMID- 21068663
TI  - Effects of early neuronal and delayed inducible nitric oxide synthase blockade on
      cardiovascular, renal, and hepatic function in ovine sepsis.
AB  - BACKGROUND: Recent evidence suggests that nitric oxide produced via the neuronal
      nitric oxide synthase is involved mainly in the early response to sepsis, whereas
      nitric oxide derived from the inducible nitric oxide synthase is responsible
      during the later phase. We hypothesized that early neuronal and delayed inducible
      nitric oxide synthase blockade attenuates multiple organ dysfunctions during
      sepsis. METHODS: Sheep were randomly allocated to sham-injured, nontreated
      animals (n = 6); injured (48 breaths of cotton smoke and instillation of
      Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured
      animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h
      and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n =
      6). RESULTS: The injury induced arterial hypotension, vascular leakage,
      myocardial depression, and signs of renal and hepatic dysfunctions. The treatment
      significantly attenuated, but did not fully prevent, the decreases in mean
      arterial pressure and left ventricular stroke work index. Although the elevation
      of creatinine levels was partially prevented, the decreases in urine output and
      creatinine clearance were not affected. The injury-related increases in bilirubin
      levels, international normalized ratio, and lipid peroxidation in liver tissue
      were significantly attenuated. Although plasma nitrite/nitrate levels were
      significantly increased versus baseline from 12-24 h in controls, plasma
      nitrite/nitrate levels were not increased in treated animals. CONCLUSIONS: The
      combination treatment shows potential benefit on sepsis-related arterial
      hypotension and surrogate parameters of organ dysfunctions in sheep. It may be
      crucial to identify the time course of expression and activation of different
      nitric oxide synthase isoforms in future investigations.

PMID- 21068664
TI  - Cerebral arterial and venous contributions to tissue oxygenation index measured
      using spatially resolved spectroscopy in newborn lambs.
AB  - BACKGROUND: Bedside assessments of cerebral oxygenation are sought to monitor
      cerebral injury in patients undergoing intensive care. Spatially resolved
      spectroscopy measures tissue oxygenation index (TOI, %) which reflects mixed
      cerebral arterial and venous oxygenations. We aimed to evaluate arterial and
      venous components of TOI (cerebral arterial to venous volume ratio [A:V ratio])
      in the newborn lamb brain using cerebral arterial and venous blood samples, and
      to investigate the impact of acute hypoxemia on the A:V ratio and TOI. METHOD:
      Nine lambs were ventilated with varied inspired oxygen to generate arterial
      oxygen saturations between 25% and 100%. Cerebral arterial and venous oxygen
      saturations analyzed using cooximeter of arterial and superior sagittal sinus
      blood were used to estimate TOI (TOIcox), assuming cerebral A:V ratio of 25:75.
      TOIcox was compared with the TOI measured by spatially resolved spectroscopy
      (TOIsrs). Actual cerebral arterial and venous volume fractions were reestimated
      using TOIsrs = cerebral arterial volume fraction cerebral arterial oxygen
      saturation + cerebral venous volume fraction*cerebral venous oxygen saturation.
      RESULTS: Median (range) TOIsrs was 48.5% (32.0-64.1%), and TOIcox was 48.4% (13.7
      74.4%), and the two were significantly correlated (R = 0.77). The mean difference
      between TOIsrs and TOIcox was 2.4% (limits of agreement +/- 18.1%). The TOIsrs -
      TOIcox difference varied with oxygen saturations, with TOIsrs higher than TOIcox
      at low saturations, and lower at high saturations. Cerebral arterial volume
      fraction was 22.9-27.5% in normoxia and markedly increased in hypoxemia.
      CONCLUSION: TOI corresponds with cerebral oxygenation. The variable agreement of
      TOIsrs with TOIcox may reflect changes in cerebral A:V ratio due to arterial
      oxygenation-related vasoreactivity.

PMID- 21068666
TI  - Sevoflurane-induced preconditioning: impact of protocol and aprotinin
      administration on infarct size and endothelial nitric-oxide synthase
      phosphorylation in the rat heart in vivo.
AB  - BACKGROUND: Sevoflurane induces preconditioning (SevoPC). The effect of aprotinin
      and the involvement of endothelial nitric-oxide synthase (NOS) on SevoPC are
      unknown. We investigated (1) whether SevoPC is strengthened by multiple
      preconditioning cycles, (2) whether SevoPC is blocked by aprotinin, and (3)
      whether endothelial NOS plays a crucial role in SevoPC. METHODS: Anesthetized
      male Wistar rats were randomized to 15 groups (each n = 6) and underwent 25-min
      regional myocardial ischemia and 2-h reperfusion. Controls were not treated
      further. Preconditioning groups inhaled 1 minimum alveolar concentration of
      sevoflurane for 5 min (SEVO-I), twice for 5 min each (SEVO-II), three times for 5
      min each (SEVO-III), or six times for 5 min each (SEVO-VI). Aprotinin was
      administered with and without sevoflurane. Involvement of endothelial NOS was
      determined with the nonspecific NOS blocker N-nitro-l-arginine-methyl-ester, the
      specific neuronal NOS blocker 7-nitroindazole, and the specific inducible NOS
      blocker aminoguanidine. RESULTS: SevoPC reduced infarct size in all protocols
      (SEVO-I, 42 +/- 6%; SEVO-II, 33 +/- 4%; SEVO-III, 11 +/- 5%; SEVO-VI, 16 +/- 4%;
      all P < 0.001 vs. control, 67 +/- 3%) and was least after three and six cycles of
      sevoflurane (P < 0.001 vs. SEVO-II and -I, respectively). Aprotinin alone had no
      effect on infarct size but blocked SevoPC. N-nitro-l-arginine-methyl-ester
      abolished SevoPC (67 +/- 4%; P < 0.05 vs. SEVO-III). Aminoguanidine and 7
      nitroindazole blocked SevoPC only partially (25 +/- 6 and 31 +/- 6%,
      respectively; P < 0.05 vs. SEVO-III and control). SevoPC induced endothelial NOS
      phosphorylation, which was abrogated by aprotinin. CONCLUSION: SevoPC is
      strengthened by multiple preconditioning cycles, and phosphorylation of
      endothelial NOS is a crucial step in mediating SevoPC. These effects are
      abolished by aprotinin.

PMID- 21068668
TI  - Effect of Helicobacter pylori infection on growth velocity of school-age Andean
      children.
AB  - BACKGROUND: Helicobacter pylori infection affects about half of the world's
      population and is usually acquired in childhood. The infection has been
      associated with chronic gastritis, peptic ulcer, and stomach cancer in adulthood.
      Little is known, however, about its consequences on child health. We examined the
      effect of H. pylori infection on growth among school-age children in the
      Colombian Andes by comparing growth velocity in the presence and absence of H.
      pylori infection. METHODS: Children who were 4-8 years old in 2004 were followed
      up in a community where infected children received anti-H. pylori treatment (n =
      165) and a comparison community (n = 161) for a mean of 2.5 years. Anthropometry
      measurements were made every 3 months and H. pylori status ascertained by urea
      breath test every 6 months. Growth velocities (cm/month) were compared across
      person-time with and without infection, using mixed models for repeated measures.
      RESULTS: In the untreated community, 83% were H. pylori-positive at baseline and
      89% were -positive at study end. The corresponding prevalences were 74% and 46%,
      respectively, in the treated community. Growth velocity in the pretreatment
      interval was 0.44 (standard deviation [SD] = 0.13) cm/month. Models that adjusted
      for age, sex, and height estimated that H. pylori-positive children grew on
      average 0.022 cm/month (95% confidence interval = 0.008 to 0.035) slower than H.
      pylori-negative children, a result that was not appreciably altered by adjustment
      for socioenvironmental covariates. CONCLUSIONS: This study suggests that chronic
      H. pylori infection is accompanied by slowed growth in school-age Andean
      children.

PMID- 21068667
TI  - Abuse in childhood and risk of uterine leiomyoma: the role of emotional support
      in biologic resilience.
AB  - BACKGROUND: Childhood adversities are associated with adult health. We
      hypothesize that exposure to physical and sexual abuse in childhood and
      adolescence will be associated with incidence of clinically symptomatic uterine
      leiomyomas (fibroids) through influences on health behaviors and reproductive
      hormone regulation. METHODS: Participants included 68,505 women enrolled in the
      Nurses' Health Study II, an ongoing prospective cohort study of premenopausal
      women from 14 US states aged 25-42 years at enrollment (1989), who completed a
      retrospective questionnaire on childhood violence exposure (2001). A cumulative
      indicator of severity and chronicity of child/teen violence exposure was derived
      using factor analysis. We used a Cox proportional-hazards model to estimate the
      incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: During
      the 728,865 woman-years of follow-up (1989-2005), 9823 incident diagnoses of
      ultrasound- or hysterectomy-confirmed uterine leiomyomas were reported; 65%
      reported any physical or sexual abuse. A dose-response association between
      cumulative abuse and fibroid risk was found. Compared with those who reported no
      abuse, multivariable IRRs for ultrasound or hysterectomy-confirmed uterine
      leiomyomas were 1.08 (95% CI = 1.03-1.13), 1.17 (1.10-1.24), 1.23 (1.14-1.33),
      1.24 (1.10-1.39), and 1.36 (1.18-1.54), for cumulative exposures ranging from
      mildest to most severe. Increased emotional support in childhood also attenuated
      associations. CONCLUSIONS: Severity and chronicity of child/teen sexual and
      physical abuse was associated with increasing risk of clinically detected
      fibroids among premenopausal women.

PMID- 21068669
TI  - A method for detection of residual confounding in time-series and other
      observational studies.
AB  - BACKGROUND: A difficult issue in observational studies is assessment of whether
      important confounders are omitted or misspecified. In this study, we present a
      method for assessing whether residual confounding is present. Our method depends
      on availability of an indicator with 2 key characteristics: first, it is
      conditionally independent (given measured exposures and covariates) of the
      outcome in the absence of confounding, misspecification, and measurement errors;
      second, it is associated with the exposure and, like the exposure, with any
      unmeasured confounders. METHODS: We demonstrate the method using a time-series
      study of the effects of ozone on emergency department visits for asthma in
      Atlanta. We argue that future air pollution may have the characteristics
      appropriate for an indicator, in part because future ozone cannot have caused
      yesterday's health events. Using directed acyclic graphs and specific causal
      relationships, we show that one can identify residual confounding using an
      indicator with the stated characteristics. We use simulations to assess the
      discriminatory ability of future ozone as an indicator of residual confounding in
      the association of ozone with asthma-related emergency department visits.
      Parameter choices are informed by observed data for ozone, meteorologic factors,
      and asthma. RESULTS: In simulations, we found that ozone concentrations 1 day
      after the emergency department visits had excellent discriminatory ability to
      detect residual confounding by some factors that were intentionally omitted from
      the model, but weaker ability for others. Although not the primary goal, the
      indicator can also signal other forms of modeling errors, including substantial
      measurement error, and does not distinguish between them. CONCLUSIONS: The
      simulations illustrate that the indicator based on future air pollution levels
      can have excellent discriminatory ability for residual confounding, although
      performance varied by situation. Application of the method should be evaluated by
      considering causal relationships for the intended application, and should be
      accompanied by other approaches, including evaluation of a priori knowledge.

PMID- 21068670
TI  - Cystic fibrosis testing 8 years on: lessons learned from carrier screening and
      sequencing analysis.
AB  - PURPOSE: This study reviews data from our cystic fibrosis testing program to
      evaluate the performance of population-based carrier screening and compare
      observed detection rates with predicted results of the American College of
      Medical Genetics/American College of Obstetricians and Gynecologists recommended
      panel of 23 mutations. METHODS: We queried our proprietary databases containing
      approximately 3 million cystic fibrosis screening tests, 1300 prenatal diagnostic
      tests, and 2400 cystic fibrosis sequencing analyses. RESULTS: We observed an
      overall cystic fibrosis carrier frequency of 1:37.6 individuals in the pan-ethnic
      tested population. This represents a detection rate of 77%, given an estimated US
      pan-ethnic carrier frequency of 1:29. For patients self-identified as white or
      Ashkenazi Jewish, a carrier frequency of 1:29 and 1:27 were observed,
      respectively. A combined frequency of 1:28, representing close to 90% of
      carriers, was identified in these two highest risk populations. In total, 119
      affected fetuses were identified by prenatal diagnoses, a ratio of 1 affected
      fetus per 25,000 carrier screens. Of 62 newborns with positive immunoreactive
      trypsinogen and positive sweat tests, almost all of whom had been tested using
      the American College of Medical Genetics/American College of Obstetricians and
      Gynecologists panel, only two individuals would have been identified using an
      expanded mutation panel. CONCLUSION: The American College of Medical
      Genetics/American College of Obstetricians and Gynecologists panel of 23
      mutations is performing as predicted in detecting cystic fibrosis carriers in the
      United States among all ethnic groups. No recurrent mutations have been detected
      in sufficient numbers to justify including any additional mutations to the
      existing panel. An expanded American College of Medical Genetics/American College
      of Obstetricians and Gynecologists panel would have a minimal impact on the
      prevention of births of children affected with cystic fibrosis.

PMID- 21068671
TI  - Unleashing the power of human genetic variation knowledge: New Zealand
      stakeholder perspectives.
AB  - PURPOSE: This study aimed to characterize the challenges in using genetic
      information in health care and to identify opportunities for improvement.
      METHODS: Taking a grounded theory approach, semistructured interviews were
      conducted with 48 participants to collect multiple stakeholder perspectives on
      genetic services in New Zealand. RESULTS: Three themes emerged from the data: (1)
      four service delivery models were identified in operation, including both those
      expected models involving genetic counselors and variations that do not route
      through the formal genetic service program; (2) multiple barriers to sharing and
      using genetic information were perceived, including technological,
      organizational, institutional, legal, ethical, and social issues; and (3)
      impediments to wider use of genetic testing technology, including variable
      understanding of genetic test utilities among clinicians and the limited capacity
      of clinical genetic services. Targeting these problems, information technologies
      and knowledge management tools have the potential to support key tasks in genetic
      services delivery, improve knowledge processes, and enhance knowledge networks.
      CONCLUSION: Because of the effect of issues in genetic information and knowledge
      management, the potential of human genetic variation knowledge to enhance health
      care delivery has been put on a "leash."

PMID- 21068672
TI  - Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related
      Kaposi sarcoma.
AB  - Using a novel blinded intrapatient vehicle control design, we conducted a phase
      II study of topically administered halofuginone, an angiogenesis inhibitor that
      inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with
      AIDS-related Kaposi sarcoma. Serial Kaposi sarcoma biopsies assessed treatment
      effects on angiogenic factors and Kaposi sarcoma herpesvirus-latency associated
      nuclear antigen-1 (KSHV-LANA). We observed marked heterogeneity of KSHV-LANA
      expression. Although the small number of subjects whose response could be
      evaluated precluded definitive assessment of halofuginone's efficacy, we observed
      a significant decrease in type-I collagen only in halofuginone-treated lesions,
      but no effect on MMP-2. The trial design is applicable to future studies of
      topical agents.

PMID- 21068673
TI  - Effect of hormonal contraceptive use before HIV seroconversion on viral load
      setpoint among women in Rakai, Uganda.
AB  - BACKGROUND: High viral load (VL) setpoint is a marker for rapid HIV progression.
      Few studies have examined whether use of hormonal contraception (HC) prior to HIV
      seroconversion affects VL setpoint. METHODS: We determined VL setpoints in 285
      HIV seroconverters using blood samples collected 6 months or more after estimated
      HIV seroconversion but before disease progression to CD4 <= 250 or WHO Stage 3 or
      4. We used multivariate linear regression to estimate the effect of HC use before
      HIV seroconversion on VL setpoint, and multivariate Cox regression to estimate
      the hazards ratio of death associated with VL setpoint. RESULTS: Of 285 women, 42
      (15%) reported using HC before HIV seroconversion. Mean VL setpoint was 4.49 (SD
      0.79) log10 copies per milliliter among women who used HC before HIV
      seroconversion and 4.47 (SD 0.86) among non-HC users (P = 0.88). In multivariate
      analysis, HC before HIV seroconversion was not associated with VL setpoint (+0.11
      log10 copies/mL; P = 0.47). Higher socioeconomic status was associated with lower
      VL setpoint (-0.43 log10 copies/mL; P = 0.04). VL setpoints above the median were
      associated with faster time to death (adjHR: 2.54, 95% confidence interval: 1.30
      to 4.98, P < 0.01). CONCLUSIONS: Use of HC before HIV seroconversion was not
      associated with elevated VL setpoint.

PMID- 21068675
TI  - A highly sensitive and specific model for predicting HIV-1 tropism in treatment
      experienced patients combining interpretation of V3 loop sequences and clinical
      parameters.
AB  - BACKGROUND: Phenotypic assays are considered the gold standard for HIV-1 tropism
      assessment. However, they are expensive and not widely available. Genotypic
      assays may provide an easier alternative, but their sensitivity remains low. We
      hypothesize that combining clinical data with V3 sequences may improve the
      diagnostic accuracy of genotypic tools. METHODS: We analyzed clinical and
      biological data from 159 HIV-1-infected adults, 88 (56%) of whom were treatment
      experienced. Coreceptor phenotype was performed with Trofile and ES Trofile
      assay. V3 loop sequences were interpreted according to genotypic algorithms
      available at website. Multivariate logistic regression analyses were used to
      identify variables predicting HIV-1 tropism. Cut-off values for the prediction of
      CXCR4-using virus were defined. RESULTS: A total of 170 samples with phenotypic
      and genotypic determination of HIV-1 tropism were included. When only treatment
      experienced patients were selected, a predictive model of HIV-1 tropism had an
      area under the receiver operating characteristic curve of 0.966 (95% confidence
      interval: 0.930 to 1.000, P < 0.001). The equation of the model included 2
      bioinformatic tools (Geno2pheno-clinical model and net charge rule), the false
      positive rate score of Geno2pheno, and the following clinical data: exposure to
      more than 3 antiretroviral classes, years since HIV infection diagnosis and log10
      HIV-1 RNA. A cut-off value >= 5.75 showed the highest accuracy to predict CXCR4
      usage (96.6% sensitivity and 92.3% specificity). CONCLUSIONS: A genotypic
      clinical model is highly accurate in predicting phenotypic tropism of HIV-1 in
      treatment-experienced patients. This may provide a cheap and rapid tool to select
      candidates for treatment with CCR5 antagonists in a routine clinical setting.

PMID- 21068674
TI  - The clinical impact and cost-effectiveness of routine, voluntary HIV screening in
      South Africa.
AB  - BACKGROUND: Although 900,000 HIV-infected South Africans receive antiretroviral
      therapy, the majority of South Africans with HIV remain undiagnosed. METHODS: We
      use a published simulation model of HIV case detection and treatment to examine 3
      HIV screening scenarios, in addition to current practice as follows: (1) one
      time; (2) every 5 years; and (3) annually. South African model input data include
      the following: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance
      rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate
      (including 2 sequential antiretroviral therapy regimens) for identified cases.
      Outcomes include life expectancy, direct medical costs, and incremental cost
      effectiveness. RESULTS: HIV screening one-time, every 5 years, and annually
      increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from
      180.6 months (current practice) to 184.9, 187.6, and 197.2 months. The
      incremental cost-effectiveness of one-time screening is dominated by screening
      every 5 years. Screening every 5 years and annually each have incremental cost
      effectiveness ratios of $1570/quality-adjusted life year and $1720/quality
      adjusted life year. Screening annually is very cost-effective even in settings
      with the lowest incidence/prevalence, with test acceptance and linkage rates both
      as low as 20%, or when accounting for a stigma impact at least four-fold that of
      the base case. CONCLUSIONS: In South Africa, annual voluntary HIV screening
      offers substantial clinical benefit and is very cost-effective, even with highly
      constrained access to care and treatment.

PMID- 21068676
TI  - The effects of polyethylene glycosylated creatine supplementation on muscular
      strength and power.
AB  - The purpose of the present investigation was to examine the effects of 28 days of
      polyethylene glycosylated creatine (PEG-creatine) supplementation on 1-repetition
      maximum bench press (1RMBP) and leg extension (1RMLE), mean power (MP), and peak
      power (PP) from the Wingate Anaerobic test and body weight (BW). This study used
      a randomized, double-blind, placebo-controlled, parallel design. Twenty-two
      untrained men (mean age +/- SD = 22.1 +/- 2.1 years) were randomly assigned to
      either a Creatine (n = 10) or Placebo (n = 12) group. The Creatine group ingested
      PEG-creatine (5 g.d), whereas the Placebo group ingested maltodextrin powder (5
      g.d). All subjects performed bench press and bilateral leg extension exercises to
      determine their 1RM values, and 2 consecutive Wingate Anaerobic Tests (separated
      by 7 minutes) on a cycle ergometer to determine MP and PP before supplementation
      (day 0) and after 7 (day 7) and 28 (day 28) days of supplementation. The results
      indicated that there was a significant (p < 0.05) increase in 1RMBP between days
      0 and 28 for the Creatine group but not for the Placebo group. There were no
      significant changes, however, in 1RMLE, MP, PP, or BW for the Creatine or Placebo
      group. These findings indicated that 28 days of PEG-creatine supplementation
      without resistance training increased upper body strength but not lower body
      strength or muscular power. These findings supported the use of the PEG-creatine
      supplement for increasing 1RMBP strength in untrained individuals.

PMID- 21068677
TI  - The relationship between kinematic determinants of jump and sprint performance in
      division I women soccer players.
AB  - The purpose of this study was to determine the relationship between measures of
      unilateral and bilateral jumping performance and 10- and 25-m sprint performance.
      Fifteen division I women soccer players (height 165 +/- 2.44 cm, mass 61.65 +/-
      7.7 kg, age 20.19 +/- 0.91 years) volunteered to participate in this study. The
      subjects completed a 10- and 25-m sprint test. The following jump kinematic
      variables were measured using accelerometry: sprint time, step length, step
      frequency, jump height and distance, contact time, concentric contact time, and
      flight time (Inform Sport Training Systems, Victoria, BC, Canada). The following
      jumps were completed in random order: bilateral countermovement vertical jump,
      bilateral countermovement horizontal jump, bilateral 40-cm drop vertical jump,
      bilateral 40-cm drop horizontal jump, unilateral countermovement vertical jump
      (UCV), unilateral countermovement horizontal jump, unilateral 20-cm drop vertical
      jump (UDV), and unilateral 20-cm drop horizontal jump (UDH). The trial with the
      best jump height or distance, reactive strength (jump height or distance/total
      contact time), and flight time to concentric contact time ratio (FT/CCT) was
      recorded to analyze the relationship between jump kinematics and sprint
      performance. None of the bilateral jump kinematics significantly correlated with
      10- and 25-m sprint time, step length, or step frequency. Right-leg jump height
      (r = -0.71, p = 0.006, SEE = 0.152 seconds), FT/CCT (r = -0.58, p = 0.04, SEE =
      0.176 seconds), and combined right and left-leg jump height (r = -0.61) were
      significantly correlated with the 25-m sprint time during the UCV. Right-leg
      FT/CCT was also significantly related to 25-m step length (r = 0.68, p = 0.03,
      SEE = 0.06 m) during the UDV. The combined right and left leg jump distance to
      standing height ratio during the UDH significantly correlated (r = -0.58) with 10
      m sprint time. In comparison to bilateral jumps, unilateral jumps produced a
      stronger relationship with sprint performance.

PMID- 21068678
TI  - Validity of a squash-specific test of multiple-sprint ability.
AB  - We examined the validity and reproducibility of a squash-specific multiple-sprint
      test. Eight male squash and 8 male soccer players performed Baker's 8 * 40-m
      sprints and a squash-specific-multiple-sprint test on separate days. The sum of
      individual sprint times in each test was recorded. Six squash and 6 soccer
      players repeated the tests 7 days later to assess reproducibility using
      intraclass correlation. In addition, 2 England Squash coaches independently
      ranked the squash players using knowledge of the player and recent performances
      in local leagues. Performance on the squash-specific (r = 0.97 and 0.90) and
      Baker's test (r = 0.95 and 0.83) was reproducible in squash and soccer players,
      respectively, and did not differ on Baker's test (mean +/- SD 72.9 +/- 3.9 and
      72.9 +/- 2.8 seconds for squash and soccer players, p = 0.969, effect size =
      0.03). Squash players (232 +/- 32 seconds) outperformed soccer players (264 +/-
      14 seconds) on the squash-specific test (p = 0.02, effect size = 1.39).
      Performance on Baker's and the squash-specific test were related in squash
      players (r = 0.98, p < 0.001) but not in soccer players (r = -0.08, p = 0.87).
      Squash-player rank correlated with performance on the squash-specific (rho =
      0.79, p = 0.02) but not the Baker's test (rho = 0.55, p = 0.16). The squash
      specific test discriminated between groups with similar non-sport-specific
      multiple-sprint ability and in squash players. In conjunction with the
      relationship between test performances, the results suggest that the squash
      specific test is a valid and reproducible measure of multiple-sprint ability in
      squash players and could be used for assessing and tracking training-induced
      changes in multiple-sprint ability.

PMID- 21068679
TI  - The impact of cold-water immersion on power production in the vertical jump and
      the benefits of a dynamic exercise warm-up.
AB  - The purpose of this study was to examine the influence of a cold treatment and a
      dynamic warm-up on lower body power in the form of a countermovement vertical
      jump (CMVJ). Nine physically active men, who were either current or ex-National
      Collegiate Athletic Association (NCAA) Division 1 athletes, consented to
      participate in the study. Using a balanced, randomized presentation and a within
      subject design, each subject performed 4 environmental and warm-up protocols
      (i.e., ambient temperature without warm-up, ambient temperature with warm-up,
      cold without warm-up, or cold with warm-up). Two sets of 3 maximal effort CMVJs
      were performed on a force plate at each testing time point. For each protocol,
      the subjects completed a pretest set of CMVJ (pretreatment [PRE]), were then
      exposed to 1 of the 2 temperature treatments, completed another set of CMVJ
      (initial [IT]), then either went through a 15-minute warm-up, or were asked to
      sit in place. Then a final set of CMVJs was completed (posttreatment [PT]). The
      primary finding in this study was that warm-up was effective in offsetting the
      negative effects of cold exposure on CMVJ power. There was a significant main
      effect for Time (PRE > PT > IT), and there was a significant (p <= 0.05) main
      effect for Trial (AMB = AMBWU > COLDWU > COLD). Because athletic competitions
      happen in various colder climates, it is important to make sure that a proper
      warm-up be completed to maximize the athlete's power output. The results of this
      study demonstrate that when athletes are exposed to cold conditions, it is
      recommended that before practice or play, a dynamic warm-up be employed to
      optimize performance.

PMID- 21068680
TI  - Surface electromyographic activation patterns and elbow joint motion during a
      pull-up, chin-up, or perfect-pullupTM rotational exercise.
AB  - This study compared a conventional pull-up and chin-up with a rotational exercise
      using Perfect.PullupTM twisting handles. Twenty-one men (24.9 +/- 2.4 years) and
      4 women (23.5 +/- 1 years) volunteered to participate. Electromyographic (EMG)
      signals were collected with DE-3.1 double-differential surface electrodes at a
      sampling frequency of 1,000 Hz. The EMG signals were normalized to peak activity
      in the maximum voluntary isometric contraction (MVIC) trial and expressed as a
      percentage. Motion analysis data of the elbow were obtained using Vicon Nexus
      software. One-factor repeated measures analysis of variance examined the muscle
      activation patterns and kinematic differences between the 3 pull-up exercises.
      Average EMG muscle activation values (%MVIC) were as follows: latissimus dorsi
      (117-130%), biceps brachii (78-96%), infraspinatus (71-79%), lower trapezius (45
      56%), pectoralis major (44-57%), erector spinae (39-41%), and external oblique
      (31-35%). The pectoralis major and biceps brachii had significantly higher EMG
      activation during the chin-up than during the pull-up, whereas the lower
      trapezius was significantly more active during the pull-up. No differences were
      detected between the Perfect.PullupTM with twisting handles and the conventional
      pull-up and chin-up exercises. The mean absolute elbow joint range of motion was
      93.4 +/- 14.6 degrees , 100.6 +/- 14.5 degrees , and 99.8 +/- 11.7 degrees  for
      the pull-up, chin-up, and rotational exercise using the Perfect.PullupTM twisting
      handles, respectively. For each exercise condition, the timing of peak muscle
      activation was expressed as a percentage of the complete pull-up cycle. A general
      pattern of sequential activation occurred suggesting that pull-ups and chin-ups
      were initiated by the lower trapezius and pectoralis major and completed with
      biceps brachii and latissimus dorsi recruitment. The Perfect.PullupTM rotational
      device does not appear to enhance muscular recruitment when compared to the
      conventional pull-up or chin-up.

PMID- 21068681
TI  - A comparison of high-speed power training and traditional slow-speed resistance
      training in older men and women.
AB  - Muscle power, the product of force * velocity, is a critical determinant of
      function in older adults. Resistance training (RT) at high speed has been shown
      to improve peak muscle power in this population; however, different functional
      tasks may benefit from the improvement of power at values other than "peak"
      values, for example, tasks that require a greater velocity component or a greater
      force component. This study compared the effect of high-speed RT on muscle
      performance (peak power [PP] and its components [PP force and PP velocity] and
      overall peak velocity [VEL]) across a broad range of external resistances. Thirty
      eight older men and women were randomized to high-speed power training at 40% of
      the 1-repetition maximum (1RM) (n = 13 [74.1 +/- 6.4 years]); traditional RT at
      80% 1RM (n = 13 [70.1 +/- 7.0 years]); or control (n = 12 [72.8 +/- 4.1 years]).
      Measures of muscle performance were obtained at baseline and after the 12-week
      training intervention. Muscle power and 1RM strength improved similarly with both
      high-speed and traditional slow-speed RT. However, speed-related muscle
      performance characteristics, PP velocity and overall VEL, were most positively
      impacted by high-speed power training, especially at lower external resistances.
      Because gains in speed-related measures with high-speed training compared to
      traditional RT do not come at the expense of other muscle performance outcomes,
      we recommend using an RT protocol in older adults that emphasizes high-speed
      movements at low external resistances.

PMID- 21068682
TI  - Fructose addition to a glucose supplement modifies perceived exertion during
      strength and endurance exercise.
AB  - The addition of fructose (F) to a glucose (G) supplement may modify the metabolic
      response during exercise; however, its effect on perceived exertion (PE) and its
      influence on postprandial metabolism have not been jointly studied in different
      types of exercise. This study sought to assess the acute effects of F addition to
      a G supplement on PE and on the postprandial metabolic response during a single
      bout of either strength exercise (SE) or endurance exercise (EE). Twenty
      physically trained men ingested an oral dose of G or GF 15 minutes before
      starting a 30-minute session of SE (10 sets of 10 repetitions of half squat) or
      EE (cycling). The combination resulted in 4 randomized interventions in a
      crossover design in which all subjects performed all experimental conditions: G +
      SE, GF + SE, G + EE, and GF + SE. Perceived exertion, heart rate (HR), G,
      insulin, lactate, and urinary catecholamine levels were measured before exercise,
      during the exercise, and during acute recovery. Perceived exertion during
      exercise was lower for GF than for G during SE and EE (mean +/- SD; 8.95 +/- 0.62
      vs. 9.26 +/- 0.65, p < 0.05 and 7.47 +/- 0.84 vs. 7.74 +/- 0.93, p < 0.05,
      respectively). The glycemic peak in GF + SE was lower than in G + SE (p < 0.05),
      and there was a second peak during recovery (p < 0.05), whereas in EE, no
      difference in blood G levels was noted between G and GF supplements. Moreover,
      HR, urinary adrenalin, and noradrenalin were lower in GF than in G (p < 0.05),
      though only for EE. The results showed that PE is positively affected by GF
      supplementation for both SE and EE and thus may be a useful dietary strategy for
      helping to achieve higher training loads.

PMID- 21068683
TI  - Relationship between endurance field tests and match performance in young soccer
      players.
AB  - The purpose of this study was to examine the relationship between popular
      endurance field tests and physical match performance in elite male youth soccer
      players. Eighteen young male soccer players (age 14.4 +/- 0.1 years, height 1.67
      +/- 4.8 cm, body mass 53.6 +/- 1.8 kg) were randomly chosen among a population of
      elite-level soccer players. Players were observed during international
      championship games of the corresponding age categories and randomly submitted to
      the level 1 of the Yo-Yo intermittent recovery test (Yo-Yo IR1), the Multistage
      Fitness Test (MSFT), and the Hoff test on separate occasions. Physical and
      physiological match demands were assessed using Global Positioning System
      technology and short-range telemetry (GPS Elite, Canberra, Australia),
      respectively. Players covered 6,087 +/- 582 m (5,098-7,019 m) of which 15% (930
      +/- 362 m; 442-1,513) were performed as a high-intensity activity. During the
      first and second halves, players attained 86.8 +/- 6.5 and 85.8 +/- 5.8% of
      maximum heart rate (HRmax; p = 0.17) with peak HRs of 100 +/- 2 and 99.4 +/- 3.2%
      of HRmax, respectively. Players' Yo-Yo IR1 and MSFT performance were
      significantly related (r = 0.62-0.76) to a number of match physical activities.
      However, the Hoff test was only significantly related with sprint distance (r =
      0.70, p = 0.04). The Yo-Yo IR1 showed a very large association with MSFT
      performance (r = 0.89, p < 0.0001). The results of this study showed that the Yo
      Yo IR1 and MSFT may be regarded as valuable tests to assess match fitness and
      subsequently guide training prescription in youth soccer players. The very strong
      relationship between Yo-Yo IR1 and MSFT suggests their use according to the
      period of the season and the aerobic fitness level of the players. Because of the
      association of the Yo-Yo IR1 and MSFT with match physical performances, these
      tests should be considered in talent selection and development of players.

PMID- 21068684
TI  - Upper body muscle strength and batting performance in cricket batsmen.
AB  - The aim of this study was to determine if upper body muscle strength (as measured
      by the 1 repetition maximum bench press) was associated with cricket batting
      performance. Cricket batting performance was defined by the maximum hitting
      distance during a batting task and batting average and strike rate during 1-Day
      and Twenty/20 (T/20) matches. Eighteen, provincial level, elite cricket batsmen
      participated in the study. Upper body muscle strength was found to be positively
      correlated with maximum hitting distance (p = 0.0052). There were no significant
      correlations between upper body strength, batting average, and strike rate for
      both the 1-Day and T/20 matches. The results of this study have implications for
      coaches choosing a particular batting line-up. Batsmen who have stronger upper
      bodies could be favored to bat when a match situation requires them to hit
      powerful strokes resulting in boundaries. However, coaches cannot use upper body
      strength as a predictor of overall batting performance in 1-Day or T/20 matches.

PMID- 21068685
TI  - Latent effect of passive static stretching on driver clubhead speed, distance,
      accuracy, and consistent ball contact in young male competitive golfers.
AB  - This investigation was conducted to determine the effect of 2 different warm-up
      treatments over time on driver clubhead speed, distance, accuracy, and consistent
      ball contact in young male competitive golfers. Two supervised warm-up
      treatments, an active dynamic warm-up with golf clubs (AD) and a 20-minute total
      body passive static stretching routine plus an identical AD warm-up (PSS), were
      applied before each performance testing session using a counterbalanced design on
      nonconsecutive days. Immediately after the AD treatment, subjects were instructed
      to hit 3 full swing golf shots with their driver with 1-minute rest between
      trials. Immediately after the PSS treatment, subjects were instructed to hit 3
      full-swing golf shots with their driver at t0 and thereafter at t15, t30, t45,
      and t60 minutes with 1-minute rest between swing trials to determine any latent
      effects of PSS on golf driver performance measures. Results of paired t-tests
      revealed significant (p < 0.05) decreases in clubhead speed at t0 (-4.92%), t15 (
      2.59%), and t30 (-2.19%) but not at t45 (-0.95) or t60 (-0.99). Significant
      differences were also observed in distance at t0 (-7.26%), t15 (-5.19%), t30 (
      5.47%), t45 (-3.30%), and t60 (-3.53%). Accuracy was significantly impaired at t0
      (61.99%), t15 (58.78%), t30 (59.46%), and t45 (61.32%) but not at t60 (36.82%).
      Finally, consistent ball contact was significantly reduced at t0 (-31.29%), t15 (
      31.29%), t30 (-23.56%), t45 (-27.49%), and t60 (-15.70%). Plausible explanations
      for observed performance decrements include a more compliant muscle-tendon unit
      (MTU) and an altered neurological state because of the PSS treatment. Further,
      the findings of this study provide evidence supporting the theory that the
      mechanical properties of the MTU may recover at a faster rate than any associated
      neurological changes. The results of this inquiry strongly suggest that a total
      body passive static stretching routine should be avoided before practice or
      competition in favor of a gradual AD. Athletes with poor mechanics because of
      lack of flexibility should perform these exercises after a conditioning session,
      practice, or competition.

PMID- 21068686
TI  - iPods--a surrogate coach for junior and subelite athletes: new ideas based on a
      review of the literature.
AB  - The global proliferation of MP3 players such as iPods means coaches have an
      opportunity to access a tool to enhance coaching that much of the population
      already use widely, without considerable increase in investment of time or money.
      Research evidence strongly indicates that music has the ability to influence
      psychological and physiological factors and can improve performance measures
      significantly. Additionally, the nature of athlete's self-talk could possibly be
      influenced through the use of 'digiprompts,' resulting in more focused and
      productive training sessions. Research evidence also indicates a limited effect
      on athlete adaptation during unsupervised training sessions related to decreased
      training frequency and intensity. Coaches should always look for ways to enhance
      their coaching, but new technologies and methodologies will only be widely
      accepted if seen by the coaching community as readily accessible and able to
      facilitate efficient improvement in coaching methodologies and athlete
      development. With technological advances in music delivery systems and digital
      editing, digital media and delivery systems for distance coaching should be
      explored. This paper reviews several fields of research in an attempt to
      highlight how the use of what is now common digital technology can create a
      'surrogate coach.' Through the development of structured and specific digital
      training aids, the effects of music as an ergogenic aid means the use of MP3
      players seems a logical step forward for coaches, and unsupervised training could
      potentially be made more effective.

PMID- 21068687
TI  - Effects of a 4-week youth baseball conditioning program on throwing velocity.
AB  - Effects of a 4-week youth baseball conditioning program on throwing velocity.
      This study examined the effects of a 4-week youth baseball conditioning program
      on maximum throwing velocity. Thirty-four youth baseball players (11-15 years of
      age) were randomly and equally divided into control and training groups. The
      training group performed 3 sessions (each 75 minutes) weekly for 4 weeks, which
      comprised a sport specific warm-up, resistance training with elastic tubing, a
      throwing program, and stretching. Throwing velocity was assessed initially and at
      the end of the 4-week conditioning program for both control and training groups.
      The level of significance used was p < 0.05. After the 4-week conditioning
      program, throwing velocity increased significantly (from 25.1 +/- 2.8 to 26.1 +/-
      2.8 m.s) in the training group but did not significantly increase in the control
      group (from 24.2 +/- 3.6 to 24.0 +/- 3.9 m.s). These results demonstrate that the
      short-term 4-week baseball conditioning program was effective in increasing
      throwing velocity in youth baseball players. Increased throwing velocity may be
      helpful for pitchers (less time for hitters to swing) and position players
      (decreased time for a runner to advance to the next base).

PMID- 21068688
TI  - Estimation of human effective absorbed dose of 67Ga-cDTPA-gonadorelin based on
      biodistribution rat data.
AB  - OBJECTIVE: In this investigation, we estimated the effective absorbed dose of
      radiation into human organs, after an intravenous administration of gallium-67
      (67Ga)-labeled gonadorelin, one of the gonadotropin-releasing hormone (GnRH)
      agonists, using biodistribution data from injected normal rats. METHODS: Five
      rats were killed at exact time intervals (0.25, 0.5, 1, 2, 4, 24, and 48 h post
      injections) and the percentage of injected dose per gram of each organ was
      measured by direct counting from rat data. The Medical Internal Radiation Dose
      formulation was applied to extrapolate from rat to human and to project the
      absorbed radiation dose for various organs in humans. RESULTS: From rat data we
      estimated that a 185-MBq injection of 67Ga-cDTPA-GnRH into the humans might
      result in an estimated absorbed dose of 5.26 mGy in the whole body with the
      highest effective absorbed dose was in the lungs (2.73 mSv), and the organs that
      received the next highest doses were the bladder wall (1.59 mSv), liver (0.80
      mSv), and bone marrow (0.52 mSv). CONCLUSION: The biodistribution of 67Ga-cDTPA
      GnRH in rats showed high breast uptake and low muscle and blood uptake. These
      results suggest that it should be possible to perform early imaging of the breast
      anomalies and GnRH receptors indicating potential malignant lesions.

PMID- 21068689
TI  - Radiologic and audiologic evidence of the location of an intracochlear mass.

PMID- 21068690
TI  - Comparison of pseudobinaural hearing to real binaural hearing rehabilitation
      after cochlear implantation in patients with unilateral deafness and tinnitus.
AB  - OBJECTIVE: Up to now, treatment modalities of unilateral deafness consist of no
      treatment, conventional contralateral routing of signal (CROS), or Bone-Anchored
      Hearing Aid (BAHA) hearing aid. Cochlear implantation makes a new treatment
      modality available for patients with single-sided deafness. The aim of this study
      is to evaluate the use of unilateral electrical stimulation with normal hearing
      on the contralateral side after a period of 6 months compared with the
      preoperative unaided situation, conventional CROS, or BAHA hearing aids. STUDY
      DESIGN: Prospective design. SETTING: Tertiary referral center; cochlear implant
      (CI) program. PATIENTS: Eleven adult subjects with unilateral deafness of various
      causes were enrolled in the study. Only those patients were included in whom
      therapy with CROS hearing aid or BAHA was not successful and in whom the auditory
      nerve was found to be intact and the cochlea patent for cochlear implantation.
      INTERVENTION: All subjects were fitted in random order with a BAHA Intenso
      mounted on the softband/tension clamp or with a CROS hearing aid. After test
      periods with both devices, the subjects received a CI. MAIN OUTCOME MEASURES: The
      Hochmair-Schulz-Moser sentence test and the Oldenburg sentence test were used to
      test speech comprehension in 3 presentation configurations in the unaided
      situation, with conventional CROS and BAHA hearing aids before cochlear
      implantation as well as after 6 months with CI. Localization was assessed using
      an array of 7 speakers at head level in a frontal semicircle. Subjective
      improvement in daily life was evaluated using the Speech, Spatial and Qualities
      of Hearing Scale, the Health Utilities Index 3 and the International Outcome
      Inventory for Hearing Aids questionnaires. Tinnitus distress was measured with a
      tinnitus scale before and after CI implantation. RESULTS: The results show
      significant improvement in localization ability as well as in speech
      comprehension in most presentation configurations with the CI. Especially, there
      is no negative effect on speech comprehension if the noise is presented to the CI
      ear and speech to the normal hearing ear. With the CI, the summation and squelch
      effects are not significant, but a significant combined head shadow effect is
      seen. Speech, Spatial and Qualities of Hearing results show an overall benefit of
      wearing the CI compared with the other treatment options. The tinnitus scale
      revealed a positive effect of CI stimulation in cases of preoperative tinnitus.
      CONCLUSION: The results in these patients suggest that cochlear implantation
      improves hearing abilities in people with single-sided deafness and is superior
      to the alternative treatment options. The use of the CI does not interfere with
      speech understanding in the normal hearing ear. Our data suggest that the
      binaural integration of electric and acoustic stimulation is possible even with
      unilateral normal hearing.

PMID- 21068691
TI  - Volume and surface of the mastoid cell system in otitis media with effusion in
      children: a case-control study by three-dimensional reconstruction of computed
      tomographic images.
AB  - OBJECTIVE: To characterize the pneumatization of the temporal bone in age-matched
      healthy children and in children with otitis media with effusion (OME). STUDY
      DESIGN: Prospective case-control study. SETTING: Tertiary hospital center.
      PATIENTS: This study included 40 healthy children and 56 children with OME, with
      age ranging from 2 to 18 years. INTERVENTION: Mastoid volume and surface
      determination by 3-dimensional reconstruction of axial temporal bone computed
      tomographic images. MAIN OUTCOME MEASURE: Mastoid volume and surface area
      comparison of healthy children and children with OME. RESULTS: The mastoid cell
      system (MCS) grows continuously up to the age of 18 years, with different
      intensities. The mean +/- SD MCS volume and surface of children with OME are
      significantly lower (2.82 +/- 1.51 ml and 40.45 +/- 18.14 cm, respectively) than
      those of healthy children (10.05 +/- 5.3 ml and 84.47 +/- 37.95 cm,
      respectively). The mastoid volume and surface area of the left and right ears
      correlate well in healthy children. In children with bilateral OME, the
      ipsilateral and contralateral ears can be largely different. The ratio of surface
      and volume is constant in age groups. CONCLUSION: In children with OME, the
      functional volume of MCS acting as a pressure buffer and the surface area serving
      for gas exchange are small. In case of OME, 1 ear could be more seriously
      affected by the disease. Otitis media with effusion presumably has a negative
      effect on the mastoid pneumatization process. The surface-to-volume ratio is
      constant through chronological age and is a good indicator of a normal middle ear
      function.

PMID- 21068692
TI  - Immediate and longer term immunogenicity of a single dose of the combined
      haemophilus influenzae type B-Neisseria meningitidis serogroup C-tetanus toxoid
      conjugate vaccine in primed toddlers 12 to 18 months of age.
AB  - Hib-primed but MenC-naive toddlers (N = 433) were randomized to receive 1 dose of
      Hib-MenC-TT or separate Hib-TT and MenC-CRM197 vaccines. One month later,
      noninferiority was demonstrated for serum bactericidal anti-MenC antibodies
      (rSBA) and Hib antipolyribosylribitol phosphate (PRP) antibodies; >99% in both
      groups had rSBA titer >= 8 or anti-PRP concentration >= 0.15 MUg/mL. After 12
      months, rSBA titer >= 8 persisted in 86.7% and 76.4%, and anti-PRP concentration
      >= 0.15 MUg/mL persisted in 98.8% and 100% of children, respectively.

PMID- 21068693
TI  - IGF binding protein-3 treatment alters intestinal cell proliferation but not body
      weight of adult cystic fibrosis transmembrane conductance regulator deficient
      mice.
AB  - The intestinal phenotype of cystic fibrosis (CF) transmembrane conductance
      regulator deficient mice includes altered cell homeostasis and a distended crypt
      villus axis, which, in previous work, was inversely proportional to body weight.
      To investigate this correlation, herein, we treated CF mice with IGF binding
      protein-3 (IGFBP-3), a protein which, as it has potent effects on cell
      proliferation and apoptosis, we hypothesized would alter the intestinal cell
      homeostasis, and assessed body weight. Six-week-old C57BL/6JxBALB F2 CF and WT
      mice received recombinant human IGFBP-3 (rhIGFBP-3, 20 mg/kg) or vehicle
      treatment, and weight gain, serum protein levels, and intestinal histology were
      assessed. Administration of rhIGFBP-3 to CF mice significantly increased the
      number of Igfbp-3 positive cells in the intestine and partially reversed the
      hyperproliferative phenotype of intestinal crypts and muscularis externa, while
      not affecting apoptosis. Serum Igfbp-3 levels were increased, and Igf-I, albumin,
      and triglycerides measures were decreased in CF compared with WT mice. rhIGFBP-3
      treatment significantly increased serum albumin and triglycerides but did not
      affect weight gain in CF mice. We have identified rhIGFBP-3 treatment to reduce
      intestinal cell proliferation, resulting in decreases in crypt depth and
      muscularis externa thickness in CF mice.

PMID- 21068694
TI  - Long-term effects of neonatal treatment with dexamethasone, L-carnitine, and
      combinations thereof in rats.
AB  - Because L-carnitine (L-CAR) is a potential substitute for neonatal dexamethasone
      (DEX) with respect to the prevention of long-term side effects, rats were treated
      on d 1, 2, and 3 after birth with saline, DEX, L-CAR, half the dose of DEX, and L
      CAR + half DEX. DEX led to growth retardation, increased mortality, and severe
      kidney damage at 50 wk of age. L-CAR had no negative effects on growth, kidney
      function at 50 wk, and survival at 101 wk. Growth retardation was induced
      transiently by half DEX and permanently by L-CAR + half DEX, slightly reduced
      kidney function but no reduced life span was found in both these groups. Except
      for the DEX group, blood glucose levels were normal at 50 wk in all groups. A
      serendipitous finding was that L-CAR treatment caused one-third less food intake;
      however, these rats maintained normal body weight. In conclusion, L-CAR, a lower
      dose of DEX, and their combination caused less negative effects in later life.
      Because L-CAR + half DEX had a negative effect on growth, attention to monitor L
      CAR levels during DEX treatment of preterm newborns seems to be justified. The
      finding that neonatal L-CAR caused reduced food intake in later life warrants
      further investigation.

PMID- 21068696
TI  - Implementation of NAAT: unexpected clinical outcomes.

PMID- 21068695
TI  - Bacterial vaginosis: identifying research gaps proceedings of a workshop
      sponsored by DHHS/NIH/NIAID.
AB  - The microbiota of the human vagina can affect the health of women, their fetuses,
      and newborns. Bacterial vaginosis (BV) is the most prevalent form of vaginal
      infection in women of reproductive age, affecting 8% to 23%, and is the most
      common etiology of vaginal symptoms prompting women to seek medical care. While
      traditional cultivation has identified numerous BV-associated bacteria involved
      in these processes, recent advances in molecular biology have facilitated the
      detection and identification of bacteria without cultivation, some of which have
      not previously been described or well characterized. A more complete
      understanding of vaginal microbial populations resulting from the adoption of
      molecular tools may lead to better strategies to maintain healthy vaginal
      microbial communities-thus enhancing women's health-and will create opportunities
      to explore the role of novel bacteria in reproductive tract diseases. On November
      19-20, 2008, the NIH convened a workshop of experts in the field of research and
      clinical practice related to BV in order to discuss how these new advances should
      be interpreted and applied to research in progress and collaborations between
      relevant disciplines. This paper summarizes the presentations of this workshop
      and outlines general recommendations arising from the related discussions. Future
      studies of BV and its associated adverse outcomes should determine if specific
      combinations of organisms are more pathogenic than others, and causally
      associated with different adverse events. Moreover, determination of causality
      will depend not only on more precise categorization of the vaginal microbiota,
      but also on variations in the host environment that may be associated with
      changes in bacterial communities over time. In this report, we offer suggestions
      and recommendations that we hope will facilitate conduct of consistent approaches
      to collaborative efforts towards advancing our understanding of the vaginal
      microbiota and its impact on human health.

PMID- 21068697
TI  - Implementation of a post-cardiac arrest care bundle including therapeutic
      hypothermia and hemodynamic optimization in comatose patients with return of
      spontaneous circulation after out-of-hospital cardiac arrest: a feasibility
      study.
AB  - Patients who present to the emergency department (ED) with return of spontaneous
      circulation after cardiac arrest generally have poor outcomes. Guidelines for
      treatment can be complicated and difficult to implement. This study examined the
      feasibility of implementing a care bundle including therapeutic hypothermia (TH)
      and early hemodynamic optimization for comatose patients with return of
      spontaneous circulation after out-of-hospital cardiac arrest. The study included
      patients over a 2-year period in the ED and intensive care unit of an academic
      tertiary-care medical center. The first year (prebundle) provided a historical
      control, followed by a prospective observational period of bundle implementation
      during the second year. The bundle elements included (a) TH initiated; (b)
      central venous pressure/central venous oxygen saturation monitoring in 2 h; (c)
      target temperature in 4 h; (d) central venous pressure greater than 12 mmHg in 6
      h; (e) MAP greater than 65 mmHg in 6 h; (f) central venous oxygen saturation
      greater than 70% in 6 h; (g) TH maintained for 24 h; and (h) decreasing lactate
      in 24 h. Fifty-five patients were enrolled, 26 patients in the prebundle phase
      and 29 patients in the bundle phase. Seventy-seven percent of bundle elements
      were completed during the bundle phase. In-hospital mortality in bundle compared
      with prebundle patients was 55.2% vs. 69.2% (P = 0.29). In the bundle patients,
      those patients who received all elements of the care bundle had mortality 33.3%
      compared with 60.9% in those receiving some of the bundle elements (P = 0.22).
      Bundle patients tended to achieve good neurologic outcome compared with prebundle
      patients, Cerebral Performance Category 1 or 2 in 31 vs. 12% patients,
      respectively (P = 0.08). Our study demonstrated that a post-cardiac arrest care
      bundle that incorporates TH and early hemodynamic optimization can be implemented
      in the ED and intensive care unit collaboratively and can achieve similar
      clinical benefits compared with those observed in previous clinical trials.

PMID- 21068698
TI  - Thrombomodulin alfa in the treatment of infectious patients complicated by
      disseminated intravascular coagulation: subanalysis from the phase 3 trial.
AB  - To investigate treatment effects of thrombomodulin alfa (TM-alpha) in patients
      with disseminated intravascular coagulation (DIC) having infection as the
      underlying disease, retrospective subanalysis of a double-blind, randomized
      controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients
      (full-analysis set) having infection and/or hematologic malignancy as the
      underlying disease received either TM-alpha (0.06 mg.kg for 30 min once daily) or
      heparin (8 U.kg.h for 24 h) for 6 days using the double-dummy method. Among these
      patients, 147 patients with noninfectious comorbidity leading to severe
      thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded
      from the present analysis, and 80 patients with infectious disease and DIC were
      extracted and subjected to the present retrospective subanalysis. Disseminated
      intravascular coagulation resolution rates were determined using the DIC
      diagnostic criteria for critically ill patients at 7 days, and mortality rates
      were evaluated at 28 days. In the TM-alpha and heparin groups, DIC resolution
      rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4%
      (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered
      from DIC were 3.7% (1/27) in the TM-alpha group and 15% (3/20) in the heparin
      group. These results suggest TM-alpha may be valuable in the treatment of DIC
      associated with infection.

PMID- 21068699
TI  - Comparison of thrombelastometry with simplified acute physiology score II and
      sequential organ failure assessment scores for the prediction of 30-day survival:
      a cohort study.
AB  - Disseminated intravascular coagulation contributes to mortality of sepsis. The
      study was performed to investigate thromboelastometry as a potential predictor of
      30-day survival in severe sepsis and to compare thromboelastometry to Simplified
      Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment
      (SOFA) scores. Ninety-eight patients with severe sepsis were included in the
      cohort study. Thromboelastometry clotting time, clot formation time (CFT),
      maximum clot firmness (MCF), and alpha angle as well as SAPS II and SOFA scores
      were determined at the day of diagnosis. Thromboelastometry variables differed in
      survivors and nonsurvivors. Mean CFT was prolonged (276 +/- 194 vs. 194 +/- 109
      s, P = 0.021; mean +/- SD), and both MCF (52.7 +/- 12.1 mm vs. 57.3 +/- 11.5 mm,
      P = 0.042) and alpha angle (53.4 +/- 12.8 degrees vs. 58.9 +/- 11.8 degrees, P =
      0.028) were reduced in nonsurvivors. Clotting time and SAPS II and SOFA scores
      were not different. Thromboelastometry values were classified as normal and
      pathological, respectively, using the median of the variables as the cutoff.
      Thromboelastometry values were normal if CFT was less than 185 s, MCF was greater
      than 55 mm, and alpha was greater than 57.5 degrees. Thirty-day survival was
      85.7% when all thromboelastometry variables were normal, but 58.7% when at least
      one variable was pathological (P = 0.005). Multivariate analysis revealed that
      the absence or presence of at least one pathological thromboelastometry variable
      allows for better prediction of 30-day survival in severe sepsis than the SAPS II
      and SOFA scores (P = 0.01; odds ratio, 4.1), respectively, emphasizing the
      importance of the coagulation system in sepsis.

PMID- 21068701
TI  - Effect of calcineurin inhibitors in the outcome of liver transplantation in
      hepatitis C virus-positive recipients.
AB  - BACKGROUND: There is a paucity of good studies evaluating the impact of
      calcineurin inhibitors on posttransplantation outcome in hepatitis C virus (HCV)
      infected liver transplant (LT) recipients. METHODS: We sought to determine
      whether there are differences on posttransplantation survival and histologic
      recurrence in HCV-LT recipients based on initial immunosuppression (IS) by
      conducting a prospective study comparing tacrolimus (Tac) versus cyclosporine
      based IS in patients undergoing LT between 2001 and 2007. Protocol liver biopsies
      were performed. RESULTS: Baseline characteristics (demographics, liver function
      at LT, genotype distribution, donor, surgery, and IS except for the type of
      calcineurin inhibitor) did not differ between groups. Severe disease (defined as
      bridging fibrosis, cirrhosis, cholestatic hepatitis, or allograft loss or death
      because of recurrent disease in the first year) was present in 67 of 253 (26.5%)
      and was equally distributed in the CsA and Tac groups (27% vs. 26%; P=0.68). Two
      thirds of protocol biopsies performed at 1 year showed some fibrosis without
      differences between CsA and Tac groups (75% vs. 70%). Advanced fibrosis (bridging
      fibrosis and cirrhosis) was diagnosed in 30% CsA and 24.5% Tac patients (P=NS).
      No differences in survival at 1 and 7 years were observed (83% and 67% vs. 78%
      and 64%, respectively, P=0.4). In summary, in patients undergoing LT for HCV
      related liver disease, posttransplantation outcome is not related to the
      calcineurin inhibitor used.

PMID- 21068702
TI  - Dabigatran etexilate (Pradaxa)--a new oral anticoagulant.
AB  - The FDA has approved the oral direct thrombin inhibitor dabigatran (da big' a
      tran) etexilate (Pradaxa--Boehringer Ingelheim) for prevention of thromboembolic
      stroke in patients with non-valvular atrial fibrillation.It has been available in
      Canada (Pradax) since 2008 for prevention of thromboembolism in patients
      undergoing knee or hip replacement surgery and was recently approved there for
      use in atrial fibrillation.

PMID- 21068703
TI  - A new botulinum toxin (Xeomin) for cervical dystonia and blepharospasm.
AB  - The FDA has approved incobotulinumtoxinA (Xeomin--Merz) for treatment of cervical
      dystonia and blepharospasm in adults. It has been commercially available in
      Germany since 2005. Several formulations of botulinum toxin type A (Botox;
      Dysport) and type B (Myobloc) are already marketed for treatment of cervical
      dystonia. Botox is also approved for treatment of blepharospasm.

PMID- 21068704
TI  - Extended-release trazodone (Oleptro) for depression.
AB  - The FDA has approved the marketing of an extended-release formulation of
      trazodone (Oleptro--Angelini Labopharm) for treatment of major depressive
      disorder in adults. Immediate-release trazodone has been available for treatment
      of depression for many years, but is used mostly in low doses for its sedating
      effects.

PMID- 21068705
TI  - Evaluation of oxygen delivery in a patient with Berlin ExcorTM biventricular
      support.
AB  - After the implantation of a biventricular assist device hemodynamic evaluation is
      difficult. The device itself frequently does not report the real outflow as it
      does not take into account the native cardiac output. Other methods used for
      cardiac output measurements cannot be employed for technical reasons and/or
      because their measurements could be misleading. The consequences are twofold;
      firstly, cardiac output cannot be estimated with accuracy. Secondly, the adequacy
      of oxygen supply and demand cannot be assessed. In order to monitor the adequacy
      of cardiac output in patient with Berlin heart biventricular support, the authors
      propose an original non invasive method to measure mixed venous blood saturation.

PMID- 21068706
TI  - Lipid therapy for serotonin syndrome after intoxication with venlafaxine,
      lamotrigine and diazepam.
AB  - A 44-year-old woman developed coma and seizure activity after intentional
      ingestion of 200 mg diazepam, 20 g lamotrigine and 4.5 g venlafaxine. In our
      intensive care unit a distinct rigidity and hyperreflexia was observed. This
      status was not influenced by haemodialysis which was initiated directly after
      admission. Plasma concentrations of the ingested drugs were determined before
      hemodialysis was started (560 ug/L diazepam, 42.4 mg/L lamotrigine and 1254 ug/L
      venlafaxine). Eight hours after the start of haemodialysis a 150 mL (2.5 mL/kg)
      intravenous bolus of 20% lipid emulsion was given. Soon after administration of
      the lipid infusion the distinct rigidity and hyperreflexia disappeared. The
      further course was uneventful.

PMID- 21068707
TI  - Manual hyperinflation is associated with a low rate of adverse events when
      performed by experienced and trained nurses in stable critically ill patients--a
      prospective observational study.
AB  - BACKGROUND: Manual hyperinflation (MH) can be performed as part of airway
      management in intubated and mechanically ventilated patients to mobilize airway
      secretions. Although previous studies demonstrated MH to be associated with
      hemodynamic and respiratory instability, we hypothesized MH to cause fewer
      adverse events (AEs) when performed by experienced and trained nurses in stable
      critically ill patients. METHODS: The incidence and type of AEs associated with
      MH were studied in a 28-bed mixed medical-surgical Intensive Care Unit. A
      difference in mean arterial pressure (MAP) or heart rate (HR) >15%, a decrease in
      peripheral oxygen saturation (SpO2) >5%, and a change in end-tidal (et)-CO2 >20%
      were considered AEs. A decrease of MAP to <=60 mmHg, any new arrhythmia, and a
      decrease of SpO2 <=90% were all considered severe AEs. Also, all changes in
      medication were considered severe AEs. RESULTS: A total of 107 MH maneuvers in 74
      patients, performed by 57 nurses, were observed and analyzed. A total of 17 MH
      maneuvers (16%) were associated with any AE; 7 maneuvers (6%) were associated
      with a severe AE. Overall, MH did not affect MAP. MH caused a statistically
      significant but clinically irrelevant increase of HR (from 87+/-24 to 89+/-22
      bpm). In one patient the MAP dropped from 70 mmHg to 60 mmHg, requiring
      adjustment of vasopressor therapy; one patient developed ventricular tachycardia
      requiring electric cardioversion. In general, MH did not affect SpO2. In one
      patient SpO2 dropped below 90%, requiring additional oxygen supply for 10
      minutes. MH caused a statistically significant but clinically irrelevant increase
      of et-CO2 levels (from 4.4+/-0.9 to 4.5+/-1.0 kPa). Five patients developed
      anxiety/agitation during or shortly after MH, mandating additional sedation in
      four patients. Occurrence of (severe) AEs was not associated with any specific
      patient or MH characteristic. CONCLUSION: The rate of hemodynamic and respiratory
      AEs with MH is low when performed by experienced and trained nurses in stable,
      critically ill patients. MH, however, may induce or increase anxiety/agitation.
      We consider MH a safe maneuver in stable ICU patients in our setting.

PMID- 21068708
TI  - Financial aspects of sentinel lymph node biopsy in early breast cancer.
AB  - AIM: At present, early breast cancer is treated with conservative surgery of the
      primary lesion (BCS) along with axillary staging by sentinel lymph node biopsy
      (SLNB). Although the scintigraphic method is standardized, its surgical
      application is different for patient compliance, work organization, costs, and
      diagnosis related group (DRG) reimbursements. METHODS: We compared four surgical
      protocols presently used in our region: (A) traditional BCS with axillary lymph
      node dissection (ALND); (B) BCS with SLNB and concomitant ALND for positive
      sentinel nodes (SN); (C) BCS and SLNB under local anaesthesia with subsequent
      ALND under general anaesthesia according to the SN result; (D) SLNB under local
      anaesthesia with subsequent BCS under local anaesthesia for negative SN, or ALND
      under general anaesthesia for positive SN. For each protocol, patient compliance,
      use of consumables, resources and time spent by various dedicated professionals,
      were analyzed. Furthermore, a detailed breakdown of 1-/2-day hospitalization
      costs was calculated using specific DRGs. RESULTS: We reported a mean costs
      variation that ranged from 1,634 to 2,221 Euros (protocols C and D). The number
      of procedures performed and the pathologists' results are the most significant
      variables affecting the rate of DRG reimbursements, that were the highest for
      protocol D and the lowest for protocol B. CONCLUSIONS: In our experience protocol
      C is the most suitable in terms of patient compliance, impact of surgical
      procedures, and work organization, and is granted by an appropriate DRG. We
      observed that a multidisciplinary approach enhances overall patient care and that
      a revaluation of DRG reimbursements is opportune.

PMID- 21068709
TI  - Clinical indications to the use of (99m)Tc-EDDA/HYNIC-TOC to detect somatostatin
      receptor-positive neuroendocrine tumors.
AB  - The aim of this study was to define, retrospectively, the utility to perform
      (99m)Tc-EDDA/HYNIC-Tyr3-octreotide ((99m)Tc-EDDA/HYNIC-TOC) scan in patients with
      NET. We studied 50 consecutive patients affected by different types of NET and
      divided in two groups. Group 1: 34 patients with known lesions in which (99m)Tc
      EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the
      appropriate treatment. Group 2: 16 patients suspected of having NET or in follow
      up after surgery. Patients were injected with 370 MBq of (99m)Tc-EDDA/HYNIC-Tyr3
      octreotide and whole-body and SPET images acquired 2-3 hours after injection.
      Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity
      and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in
      group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 (99m)Tc-HYNIC
      TOC scintigraphy showed a concordance of 68% with another imaging procedure and
      in 9 patients revealed a greater number of lesions. In the second group, false
      negative results were especially found in patients with medullary thyroid cancer
      with negative radiological findings and elevated calcitonin. In conclusion,
      (99m)Tc-EDDA/HYNIC-TOC is highly indicated for in vivo histological
      characterization of known NET lesions, previously identified by other imaging
      modalities or biopsy, to plan appropriate therapy especially for patients with
      inoperable disease. In patients with only biochemical suspicion of NET and in
      those with negative markers, this scintigraphy does not significantly modify the
      clinical management.

PMID- 21068710
TI  - Preparation and pre-clinical study of 177Lu-labelled hydroxyapatite for
      application in radiation synovectomy of small joints.
AB  - AIM: We present in this paper, the preparation and pre-clinical study of 177Lu
      labelled hydroxyapatite for the application in radiation synovectomy of small
      sized joints. METHODS: 177Lu is an adequate radionuclide for therapy, having
      ability of simultaneously showing therapeutic effects and depicting images. Both
      hydroxyapatite particulates and 177Lu were prepared indigenously. RESULTS AND
      CONCLUSION: Analysis of the gamma ray spectrum showed the radionuclide purity of
      177Lu more than 99%. HA particles were synthesized and characterized by FTIR-ATR
      and X-ray diffractometry. XRD-Pattern generated by the product indicated that the
      chief inorganic phase of the sample is hydroxyapatite crystal. FTIR spectrum of
      HA powder calcined at 800 degrees C for 1h showed all the bands that can be
      assigned to phosphate and hydroxyl groups in an apatite environment. Ca/P ratio
      was determined by ICP-OES. The Ca/P ratio of 1.68 determined for HA was about
      0.6% above the stoichiometric ratio of 1.67. Particle size distribution pattern
      was obtained with the help of laser particle size analyzer and results showed
      that more than 80% of the particles bear the size in the range ideal for
      radiosynovectomy. 177Lu-labelled hydroxyapatite particulates were prepared with
      high radiochemical purity and yield. >95% labeling yield was achieved at pH 7.
      Labeled specie remained stable up to 18 days. In vitro stability >99% remained up
      to >one half life of 177Lu. Bio-evaluation of the 177Lu-HA particles was carried
      out by injecting approximate activities of 10 and 5 MBq (in 0.1 mL suspension) as
      intra-articular injection in the right knee joints of rabbit 1 and 2
      respectively. Retention of activity was studied using images of the injected
      joints with the help of a gamma camera at various intervals. In all images no
      activity was visible in any organ other than knee joints. The retention of the
      177Lu activity was followed for 772 hours (30.01 days). Leakage of activity was
      also assessed indirectly by estimating the residing time of radiopharmaceutical
      in the synovium. Half life of 177Lu-HA residing time in the knees was estimated
      to be 154 hours and 158 hours for rabbit-1 and rabbit-2 respectively. No
      significant extra articular leakage of the injected activity was observed over a
      period of one month post injection. Pre-clinical study of 177Lu-labelled
      hydroxyapatite indicated its potential for application in radiation synovectomy
      of small joints.

PMID- 21068711
TI  - A practical method for the estimation of therapeutic activity in the treatment of
      Graves' hyperthyroidism.
AB  - AIM: To test the efficacy of a practical method which allows the calculation of
      personalized activity in Graves' disease. METHODS: The method is based on
      International Commission of Radiological Protection (ICRP) 53 data. The model
      allows the prediction of the activity administered in order to release 300 Gy to
      the thyroid, once its iodine uptake and mass are known. We applied it to 289
      patients investigated by clinical examination, biochemical assessment and neck
      ultrasonography. The method was applied considering the thyroid 131I uptake and
      the ultrasound mass. The patients were followed by check of TSH, FT3, FT4 and
      clinical examination. Finally, we evaluated the difference between our dosimetric
      method and the hypothetic administration of a fix amount of 131I (185, 370 and
      600 Mbq respectively) in term of adsorbed dose. RESULTS: The average activity
      administered was 403.3+92.5 MBq with an average dose released to thyroid of
      304.9+24.8 Gy. From a statistical point of view the administration of standard
      activities (185 and 600 MBq) would represent respectively a wrong estimate of the
      optimal dose (meanly 140.8+44.7 Gy and 473.6+142.6 Gy respectively). The
      administration of a standard activity (370 MBq) would release a dose close to
      that prescribed (291.2 Gy) with a standard deviation (86.9 Gy), which is
      considerably higher than the one obtained with the dosimetric model (24.8 Gy).
      Twenty four months after radioiodine treatment, 57.8% of patients presented
      hypothyroidism, 23.2% euthyroidism and 19% of hyperthyroidism. The overall
      therapeutic efficiency was of 81%. CONCLUSION: The dosimetric method based on
      IRCP 53 data, is effective in controlling Graves' hyperthyroidism. Advantages in
      adopting this method are: dose optimization to patient, easy implementation in
      the clinical practice, low budget impact.

PMID- 21068714
TI  - [18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who
      will benefit from prolonged neo-adjuvant chemotherapy.
AB  - AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT)
      before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However
      a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT
      monitoring during na-CHT could predict early pathological response and allow the
      delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC
      unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG
      PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At
      the end of na-CHT patients were re-evaluated to undergo definitive optimal
      surgery (i.e. without post-surgical residual disease). Percentage changes in
      maximal standardized uptake value (?-SUVmax) were compared with the pathological
      response. Only patients with pathological complete response (pCR) or minimal
      residual disease (pMRD) were considered as pathological responders (pR), while
      all the other cases were considered non-responders (NR). RESULTS: Baseline FDG
      PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20).
      After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value
      equal to normal surrounding tissues uptake (<2-17), respectively. After 3
      courses, 17 (40%) patients presented ?-SUVmax=100%, (i.e. SUVmax <2): 15 of them
      (88%) subsequently resulted pR and achieved no postsurgical residual disease at
      the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor <= 1cm.
      Out of 25 patients with ?-SUVmax <100% after 3 courses, 6 (24%) were pR and 19
      (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present
      normalization of SUVmax after 3 courses of na-CT have a high likelihood of
      benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving
      optimal surgery.

PMID- 21068715
TI  - The relation between left ventricular ejection fraction and perfusion defect size
      by gated SPECT myocardial perfusion imaging in patients with coronary artery
      disease.
AB  - AIM: Left ventricular (LV) ejection fraction (EF) and perfusion defect size (PDS)
      provide independent and incremental prognostic information in patients with
      coronary artery disease (CAD). The purpose of this study was to examine the
      correlation between EF and PDS. METHODS: LVEF and PDS were measured in 96
      consecutive patients with CAD and abnormal perfusion scan using well-validated
      automated programs. The PDS was expressed as % of LV myocardium as total
      (reversible plus fixed), fixed or reversible. RESULTS: The EF was 49+/-15% (range
      17-84), the total PDS was 29+/-15% (2-77) and the fixed PDS was 20+/-13% (2-58).
      The end-diastolic volume (EDV) was 131+/-59 mL (29-342) and end-systolic volume
      (ESV) was 72+/-51 mL (4-283). There were moderate but significant correlations
      between EF and total PDS (r=-0.46, P<0.0001) and fixed PDS (r=-0.45, P<0.0001)
      but not with reversible PDS. In the subgroup analysis, the correlations were
      stronger in patients with history of prior coronary artery bypass grafting than
      without, and higher in men than women. The highest correlations were seen between
      EF and EDV in both men and women (r=-0.68 and -0.74 respectively, P<0.0001 each),
      and between EF and ESV (r =-0.80, P<0.0001). CONCLUSION: Although there is a
      statistically significant correlation between PDS and EF, the correlation is not
      strong. This observation provides supportive evidence of why PDS and EF provide
      incremental prognostic information. It also supports the incremental prognostic
      merits of LV volume measurements.

PMID- 21068716
TI  - Introduction of a new semi-quantitative index with predictive implications in
      patients with painful osseous metastases after (186)Re-HEDP therapy.
AB  - AIM: In this study, a new method has been used to predict pain response to
      (186)Re-HEDP therapy in patients suffering from painful osseous metastases, on
      the basis of a modified bone scan index and pre-therapy pain scoring. METHODS:
      Forty five patients received a total of 73 doses of (186)Re-HEDP during a period
      of pain relapse without extra-osseous disease progression. All patients were
      under stable regimen of zoledronic acid, far off other therapeutic manipulations.
      Imaging studies regarding a modified estimation of bone scan index, were applied;
      the value of the largest bony lesion (called mBSI), provided that it also
      corresponded to the most prominent site of osseous pain was taken into account,
      and a new semi-quantitative index called Double Product Value (DPV), equal to pre
      therapy pain score times mBSI was entered in the result analyses, to investigate
      any possible correlations with response endpoints. RESULTS: Favourable response
      occurred in 35/47 evaluated therapeutic doses of (186)Re-HEDP (74.5%; excellent
      response in 12 doses, 25.5%). Responders had significantly lower DPV (3.4 +/- 2.3
      vs. 10.2 +/- 6.2, P=0.0029, for non-responders). Patients with pre-therapy DPV
      <or =4, had higher probability for considerably better (HR 2.29; P<0.0001) and
      excellent (HR 7.46; P=0.009) pain response versus those with DPV>4, and also a
      longer median period of pain relief (respective mean values 5.9 versus 2.1
      months, HR 2.82; P=0.0001). CONCLUSION: DPV, as developed and implemented in this
      study proved a valuable and reproducible pre-therapy tool for assessing degree
      and duration of pain response after (186)Re-HEDP therapy.

PMID- 21068717
TI  - T-type voltage-gated calcium channels regulate the tone of mouse efferent
      arterioles.
AB  - Voltage-gated calcium channels are important for the regulation of renal blood
      flow and the glomerular filtration rate. Excitation-contraction coupling in
      afferent arterioles is known to require activation of these channels and we
      studied their role in the regulation of cortical efferent arteriolar tone. We
      used microdissected perfused mouse efferent arterioles and found a transient
      vasoconstriction in response to depolarization with potassium; an effect
      abolished by removal of extracellular calcium. The T-type voltage-gated calcium
      channel antagonists mibefradil and nickel blocked this potassium-induced
      constriction. Further, constriction by the thromboxane analogue U46619 was
      significantly inhibited by mibefradil at a concentration specific for T-type
      channels. Using PCR, we found that two channel subtypes, Ca(v)3.1 and Ca(v)3.2,
      were expressed in microdissected efferent arterioles. Ca(v)3.1 was found by
      immunocytochemistry to be located in mouse efferent arterioles, human pre- and
      postglomerular vasculature, and Ca(v)3.2 in rat glomerular arterioles. Inhibition
      of endothelial nitric oxide synthase by L-NAME or its deletion by gene knockout
      changed the potassium-elicited transient constriction to a sustained response.
      Low concentrations of nickel, an agent that blocks Ca(v)3.2, had a similar
      effect. Thus, T-type voltage-gated calcium channels are functionally important
      for depolarization-induced vasoconstriction and subsequent dilatation in mouse
      cortical efferent arterioles.

PMID- 21068719
TI  - Probing GABA receptor function in schizophrenia with iomazenil.
AB  - Several lines of evidence from post-mortem, brain imaging, and genetic studies in
      schizophrenia patients suggest that Gamma-amino butyric acid (GABA) deficits may
      contribute to the pathophysiology of schizophrenia. Pharmacological induction of
      a transient GABA-deficit state has been shown to enhance vulnerability of healthy
      subjects to the psychotomimetic effects of various drugs. Exacerbating or
      creating a GABA deficit was hypothesized to induce or unmask psychosis in
      schizophrenia patients, but not in healthy controls. To test this hypothesis, a
      transient GABA deficit was pharmacologically induced in schizophrenia patients
      and healthy controls using iomazenil, an antagonist and partial inverse agonist
      of the benzodiazepine receptor. In a double-blind, randomized, placebo-controlled
      study, clinically stable chronic schizophrenia patients (n=13) received iomazenil
      (3.7 MUg administered intravenously over 10 min). Psychosis was measured using
      the Brief Psychiatric Rating Scale and perceptual alterations were measured using
      the Clinician Administered Dissociative Symptoms Scale before and after iomazenil
      administration. These data were compared with the effects of iomazenil in healthy
      subjects (n=20). Iomazenil produced increases in psychotic symptoms and
      perceptual alterations in schizophrenia patients, but not in healthy controls.
      The greater vulnerability of schizophrenia patients to the effects of iomazenil
      relative to controls provides further support for the GABA-deficit hypothesis of
      schizophrenia.

PMID- 21068720
TI  - Immunoregulatory mechanisms of macrophage PPAR-gamma in mice with experimental
      inflammatory bowel disease.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is widely expressed
      in macrophages and has been identified as a putative target for the development
      of novel therapies against inflammatory bowel disease (IBD). Computational
      simulations identified macrophages as key targets for therapeutic interventions
      against IBD. This study aimed to characterize the mechanisms underlying the
      beneficial effects of macrophage PPAR-gamma in IBD. Macrophage-specific PPAR
      gamma deletion significantly exacerbated clinical activity and colonic pathology,
      impaired the splenic and mesenteric lymph node regulatory T-cell compartment,
      increased percentages of lamina propria (LP) CD8+ T cells, increased surface
      expression of CD40, Ly6C, and Toll-like receptor 4 (TLR-4) in LP macrophages, and
      upregulated expression of colonic IFN-gamma, CXCL9, CXCL10, IL-22, IL1RL1, CCR1,
      suppressor of cytokine signaling 3, and MHC class II in mice with IBD. Moreover,
      macrophage PPAR-gamma was required for accelerating pioglitazone-mediated
      recovery from dextran sodium sulfate (DSS) colitis, providing a cellular target
      for the anti-inflammatory effects of PPAR-gamma agonists in IBD.

PMID- 21068718
TI  - The role of TNFalpha in the periaqueductal gray during naloxone-precipitated
      morphine withdrawal in rats.
AB  - Tolerance and dependence are common complications of long-term treatment of pain
      with opioids, which substantially limit the long-term use of these drugs. The
      mechanisms underlying these phenomena are poorly understood. Studies have
      implicated the midbrain periaqueductal gray (PAG) in the pathogenesis of morphine
      withdrawal, and recent evidence suggests that proinflammatory cytokines in the
      PAG may play an important role in morphine withdrawal. Here we report that
      chronic morphine withdrawal-induced upregulation of glial fibrillary acidic
      protein (GFAP), tumor necrosis factor alpha (TNFalpha) and phosphorylation of
      ERK1/2 (pERK1/2) in the caudal ventrolateral PAG (vlPAG). Microinjection of
      recombinant TNFalpha into the vlPAG followed by intraperitoneal naloxone resulted
      in morphine withdrawal-like behavioral signs, and upregulation of pERK1/2,
      expression of Fos, and phosphorylation of cAMP response element binding (pCREB)
      protein. We used a herpes simplex virus (HSV)-based vector expressing p55 soluble
      TNF receptor (sTNFR) microinjected into the PAG to examine the role of the
      proinflammatory cytokine TNFalpha in the PAG in the naloxone-precipitated
      withdrawal response. Microinjection of HSV vector expressing sTNFR into the PAG
      before the start of morphine treatment significantly reduced the naloxone
      precipitated withdrawal behavioral response and downregulated the expression of
      GFAP and TNFalpha in astrocytes of the PAG. TNFR type I colocalized with neuronal
      pERK1/2. Microinjection of HSV vector expressing sTNFR into the PAG also
      significantly reduced the phosphorylation of both ERK1/2 and CREB, and reduced
      Fos immunoreactivity in neurons of the PAG following naloxone-precipitated
      withdrawal. These results support the concept that proinflammatory cytokines
      expressed in astrocytes in the PAG may play an important role in the pathogenesis
      of morphine withdrawal response.

PMID- 21068721
TI  - Oil spills and fish health: exposing the heart of the matter.
AB  - The chemical complexity of crude oil and its fuel products poses many important
      challenges for exposure science in marine ecosystems that support productive
      fisheries throughout the world. Meeting these challenges will enable better
      decisions on approaches to protecting and restoring these ecosystems.

PMID- 21068722
TI  - Suppression of inflammation by a synthetic histone mimic.
AB  - Interaction of pathogens with cells of the immune system results in activation of
      inflammatory gene expression. This response, although vital for immune defence,
      is frequently deleterious to the host due to the exaggerated production of
      inflammatory proteins. The scope of inflammatory responses reflects the
      activation state of signalling proteins upstream of inflammatory genes as well as
      signal-induced assembly of nuclear chromatin complexes that support mRNA
      expression. Recognition of post-translationally modified histones by nuclear
      proteins that initiate mRNA transcription and support mRNA elongation is a
      critical step in the regulation of gene expression. Here we present a novel
      pharmacological approach that targets inflammatory gene expression by interfering
      with the recognition of acetylated histones by the bromodomain and extra terminal
      domain (BET) family of proteins. We describe a synthetic compound (I-BET) that by
      'mimicking' acetylated histones disrupts chromatin complexes responsible for the
      expression of key inflammatory genes in activated macrophages, and confers
      protection against lipopolysaccharide-induced endotoxic shock and bacteria
      induced sepsis. Our findings suggest that synthetic compounds specifically
      targeting proteins that recognize post-translationally modified histones can
      serve as a new generation of immunomodulatory drugs.

PMID- 21068723
TI  - Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall.
AB  - Photoreceptors for visual perception, phototaxis or light avoidance are typically
      clustered in eyes or related structures such as the Bolwig organ of Drosophila
      larvae. Unexpectedly, we found that the class IV dendritic arborization neurons
      of Drosophila melanogaster larvae respond to ultraviolet, violet and blue light,
      and are major mediators of light avoidance, particularly at high intensities.
      These class IV dendritic arborization neurons, which are present in every body
      segment, have dendrites tiling the larval body wall nearly completely without
      redundancy. Dendritic illumination activates class IV dendritic arborization
      neurons. These novel photoreceptors use phototransduction machinery distinct from
      other photoreceptors in Drosophila and enable larvae to sense light exposure over
      their entire bodies and move out of danger.

PMID- 21068724
TI  - Growth of graphene from solid carbon sources.
AB  - Monolayer graphene was first obtained as a transferable material in 2004 and has
      stimulated intense activity among physicists, chemists and material scientists.
      Much research has been focused on developing routes for obtaining large sheets of
      monolayer or bilayer graphene. This has been recently achieved by chemical vapour
      deposition (CVD) of CH(4) or C(2)H(2) gases on copper or nickel substrates. But
      CVD is limited to the use of gaseous raw materials, making it difficult to apply
      the technology to a wider variety of potential feedstocks. Here we demonstrate
      that large area, high-quality graphene with controllable thickness can be grown
      from different solid carbon sources-such as polymer films or small molecules
      deposited on a metal catalyst substrate at temperatures as low as 800  degrees C.
      Both pristine graphene and doped graphene were grown with this one-step process
      using the same experimental set-up.

PMID- 21068725
TI  - Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ
      1.
AB  - Parkinson's disease is a pervasive, ageing-related neurodegenerative disease the
      cardinal motor symptoms of which reflect the loss of a small group of neurons,
      the dopaminergic neurons in the substantia nigra pars compacta (SNc).
      Mitochondrial oxidant stress is widely viewed as being responsible for this loss,
      but why these particular neurons should be stressed is a mystery. Here we show,
      using transgenic mice that expressed a redox-sensitive variant of green
      fluorescent protein targeted to the mitochondrial matrix, that the engagement of
      plasma membrane L-type calcium channels during normal autonomous pacemaking
      created an oxidant stress that was specific to vulnerable SNc dopaminergic
      neurons. The oxidant stress engaged defences that induced transient, mild
      mitochondrial depolarization or uncoupling. The mild uncoupling was not affected
      by deletion of cyclophilin D, which is a component of the permeability transition
      pore, but was attenuated by genipin and purine nucleotides, which are antagonists
      of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans
      and Park7 in mice), which is a gene associated with an early-onset form of
      Parkinson's disease, downregulated the expression of two uncoupling proteins
      (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium-induced uncoupling and
      increased oxidation of matrix proteins specifically in SNc dopaminergic neurons.
      Because drugs approved for human use can antagonize calcium entry through L-type
      channels, these results point to a novel neuroprotective strategy for both
      idiopathic and familial forms of Parkinson's disease.

PMID- 21068726
TI  - Planar polarized actomyosin contractile flows control epithelial junction
      remodelling.
AB  - Force generation by Myosin-II motors on actin filaments drives cell and tissue
      morphogenesis. In epithelia, contractile forces are resisted at apical junctions
      by adhesive forces dependent on E-cadherin, which also transmits tension. During
      Drosophila embryonic germband extension, tissue elongation is driven by cell
      intercalation, which requires an irreversible and planar polarized remodelling of
      epithelial cell junctions. We investigate how cell deformations emerge from the
      interplay between force generation and cortical force transmission during this
      remodelling in Drosophila melanogaster. The shrinkage of dorsal-ventral-oriented
      ('vertical') junctions during this process is known to require planar polarized
      junctional contractility by Myosin II (refs 4, 5, 7, 12). Here we show that this
      shrinkage is not produced by junctional Myosin II itself, but by the polarized
      flow of medial actomyosin pulses towards 'vertical' junctions. This anisotropic
      flow is oriented by the planar polarized distribution of E-cadherin complexes, in
      that medial Myosin II flows towards 'vertical' junctions, which have relatively
      less E-cadherin than transverse junctions. Our evidence suggests that the medial
      flow pattern reflects equilibrium properties of force transmission and coupling
      to E-cadherin by alpha-Catenin. Thus, epithelial morphogenesis is not properly
      reflected by Myosin II steady state distribution but by polarized contractile
      actomyosin flows that emerge from interactions between E-cadherin and actomyosin
      networks.

PMID- 21068731
TI  - Effects of pollution on skin aging.

PMID- 21068732
TI  - Paradoxical increase in skin inflammation in the absence of CCR4.
AB  - The chemokine receptors are seven transmembrane, G-protein-coupled surface
      receptors that play key roles in the migration and localization of leukocytes to
      the skin during physiologic and inflammatory states. Their ligands, chemokines,
      are small secreted proteins that initiate leukocyte chemoattraction. Recent data
      indicate that known subsets of T helper (Th) cells express signature chemokine
      receptors (e.g., CXCR3, CCR3/4, and CCR6) that help to define individual subsets
      such as Th1, Th2, and Th17 cells, respectively, although there is some degree of
      overlap among these T-cell subsets. In this issue, Lehtimaki et al. use an
      oxazolone-induced contact hypersensitivity (CHS) model to show that T cells (as
      well as neutrophils and eosinophils) from CCR4(-/-) mice accumulate just as (if
      not more) efficiently in inflamed skin as compared with the same population of
      leukocytes from wild-type (WT) mice. Although somewhat unexpected, their results
      can be explained if CCR4 attracts both proinflammatory and suppressive T cells
      into skin in addition to serving functions that are partially redundant with
      those of CCR10. Finally, we discuss other possible roles for CCR4 in the homing
      of T cells to skin.

PMID- 21068733
TI  - Paying "particle" attention to novel melanoma treatment strategies.
AB  - Malignant melanoma remains the deadliest form of skin cancer because of its
      highly aggressive nature and the lack of effective treatments. Recent
      investigations into alternative treatment strategies have highlighted the
      exciting potential of nanoparticles to increase melanoma cell delivery and the
      efficacy of small interfering RNAs (siRNAs) and pharmacological inhibitors. In
      this issue, Chen et al. report a new liposomal nanoparticle for c-Myc siRNA
      delivery, noting it to be highly effective in reducing c-Myc expression and
      inhibiting melanoma tumor growth in mouse models. This preclinical study
      underscores the importance of investigating nanoparticle treatment options for
      chemoresistant melanomas.

PMID- 21068734
TI  - Oxygenation state as a driver of myofibroblast differentiation and wound
      contraction: hypoxia impairs wound closure.
AB  - Myofibroblasts are ubiquitous in the human body and may form from the
      differentiation of fibroblasts, epithelial cells, endothelial cells, and
      mononuclear cells, among others. Their clinical significance could be
      substantial, depending on biomedical context. Myofibroblasts help contract open
      skin wounds, but they could also be key drivers of fibrosis across numerous
      tissue systems and support tumor invasiveness. Understanding the molecular events
      underlying myofibroblast formation is significant for many human diseases. In
      this issue, Modarressi et al. address the significance of wound tissue hypoxia in
      impairing wound contraction by compromising myofibroblast formation. They present
      compelling evidence indicating tissue hypoxia conflicts with wound closure. We
      are reminded that correcting wound tissue hypoxia is critical for the tissue's
      response to other therapeutic interventions.

PMID- 21068735
TI  - Lucky number seven: RNase 7 can prevent Staphylococcus aureus skin colonization.
AB  - Staphylococcus aureus colonization is a major risk factor for infection. In this
      issue, Simanski et al. demonstrate that the antimicrobial peptide RNase 7 is
      essential for preventing S. aureus colonization in human skin. These findings
      suggest that therapeutic interventions aimed at targeting RNase 7 production in
      the skin may be a novel strategy to protect against S. aureus infections.

PMID- 21068739
TI  - The role of blood pressure variability in misdiagnosed clinic hypertension.
AB  - Blood pressure (BP) assessment may be vulnerable to bias by increased BP
      variability. Uncertainty in determining BP control is inherent to the clinic
      setting. We analyzed a registry of 3949 patients referred for ambulatory BP
      monitoring. The difference between clinic and ambulatory readings was plotted
      against ambulatory BP variability, assessed by standard deviation. In addition,
      BP variability of patients with clinic and awake ambulatory hypertension was
      compared with that of patients with controlled BP and sustained hypertension,
      respectively. The average clinic-ambulatory systolic BP difference was 5 +/- 17/3
      +/- 9 mm  Hg. Patients with >10-mm  Hg systolic difference had higher systolic
      ambulatory BP standard deviation (14.9 +/- 4.2 mm  Hg) compared to patients with
      a difference of 0 to 10-mm  Hg (standard deviation 12.5 +/- 3.7 mm  Hg). Patients
      with masking (negative clinic-ambulatory BP difference) also had comparatively
      higher standard deviation (14.4 +/- 4.9 mm  Hg P<0.0001). Greater ambulatory BP
      variability carried increased risk for both false diagnosis of hypertension (odds
      ratio (OR): 2.09, 95% confidence interval (CI): 1.58-2.76), and missed clinic
      diagnosis of hypertension (OR: 1.86, 95% confidence interval: 1.48-2.33). The
      former was more striking in women, in whom high variability carried greater odds
      for false diagnosis of hypertension (OR: 2.76, 95% confidence interval: 1.96
      3.89). Thus, clinic misjudgment of BP control may stem in part from high BP
      variability. Women with high BP variability are more susceptible to hypertension
      misdiagnosis. It is possible that high BP variability contributes to the
      increased cardiovascular risk related to both masked hypertension and white coat
      hypertension.

PMID- 21068741
TI  - X-linked adrenoleukodystrophy: diagnostic and follow-up system in Japan.
AB  - X-linked adrenoleukodystrophy (ALD) is an intractable neurodegenerative disease
      associated with the accumulation of very long-chain saturated fatty acids (VLCFA)
      in tissues and body fluids. We have established a Japanese referral center for
      the diagnosis of ALD, using VLCFA measurements and mutation analysis of the ABCD1
      gene, and have identified 60 kinds of mutations in 69 Japanese ALD families,
      which included 38 missense mutations, 6 nonsense mutations, 8 frame-shift
      mutations, 3 amino acid deletions, 2 exon-skip mutations and 3 large deletions. A
      total of 24 kinds of mutations (40%) were identified only in Japanese patients by
      referring to the current worldwide ALD mutation database. There was no clear
      correlation between these mutations and phenotypes of 81 male patients in these
      69 families. About 12% of the individuals with ALD had de novo mutations by
      mutation analysis in the male probands and their mothers, which should be helpful
      data for genetic counseling. The only effective therapy for the cerebral form of
      ALD should be hematopoietic stem cell transplantation at the early stages of the
      cerebral symptoms, therefore, we performed presymptomatic diagnosis of ALD by
      extended familial screening of the probands with careful genetic counseling, and
      established a long follow-up system for these patients to prevent the progression
      of brain involvement and to monitor the adrenocortical insufficiency. Further
      elucidation of pathology in ALD, especially concerning the mechanisms of the
      onset of brain involvement, is expected.

PMID- 21068740
TI  - Genetic influence on blood pressure measured in the office, under laboratory
      stress and during real life.
AB  - To determine to what extent the genetic influences on blood pressure (BP)
      measured in the office, under psychologically stressful conditions in the
      laboratory and during real life are different from each other. Office BP, BP
      during a video game challenge and a social stressor interview, and 24-h
      ambulatory BP were measured in 238 European American and 186 African American
      twins. BP values across the two tasks were averaged to represent stress levels.
      Genetic model fitting showed no ethnic or gender differences for any of the
      measures. The model fitting resulted in heritability estimates of 63, 75 and 71%
      for office, stress and 24-h systolic BP (SBP) and 59, 67 and 69% for diastolic BP
      (DBP), respectively. Up to 81% of the heritability of office SBP and 71% of
      office DBP were attributed to genes that also influenced stress BP. However, only
      45% of the heritability of 24-h SBP and 49% of 24-h DBP were attributed to genes
      that also influence office BP. Similarly, about 39% of the heritability of 24-h
      SBP and 42% of 24-h DBP were attributed to genes that also influence stress BP.
      Substantial overlap exists between genes that influence BP measured in the
      office, under laboratory stress and during real life. However, significant
      genetic components specific to each BP measurement also exist. These findings
      suggest that partly different genes or sets of genes contribute to BP regulation
      in different conditions.

PMID- 21068742
TI  - Androgenetic/biparental mosaicism in a girl with Beckwith-Wiedemann syndrome-like
      and upd(14)pat-like phenotypes.
AB  - This report describes androgenetic/biparental mosaicism in a 4-year-old Japanese
      girl with Beckwith-Wiedemann syndrome (BWS)-like and paternal uniparental disomy
      14 (upd(14)pat)-like phenotypes. We performed methylation analysis for 18
      differentially methylated regions on various chromosomes, genome-wide
      microsatellite analysis for a total of 90 loci and expression analysis of SNRPN
      in leukocytes. Consequently, she was found to have an androgenetic 46,XX cell
      lineage and a normal 46,XX cell lineage, with the frequency of the androgenetic
      cells being roughly calculated as 91% in leukocytes, 70% in tongue tissues and
      79% in tonsil tissues. It is likely that, after a normal fertilization between an
      ovum and a sperm, the paternally derived pronucleus alone, but not the maternally
      derived pronucleus, underwent a mitotic division, resulting both in the
      generation of the androgenetic cell lineage by endoreplication of one blastomere
      containing a paternally derived pronucleus and in the formation of the normal
      cell lineage by union of paternally and maternally derived pronuclei. It appears
      that the extent of overall (epi)genetic aberrations exceeded the threshold level
      for the development of BWS-like and upd(14)pat-like phenotypes, but not for the
      occurrence of other imprinting disorders or recessive Mendelian disorders.

PMID- 21068743
TI  - Prostate Cancer and Prostatic Diseases. Editor's comments.

PMID- 21068745
TI  - NIMH-funded pragmatic trials: moving on.

PMID- 21068752
TI  - The TRAF-interacting protein (TRIP) is a regulator of keratinocyte proliferation.
AB  - The TRAF-interacting protein (TRIP/TRAIP) is a RING-type E3 ubiquitin ligase
      inhibiting tumor necrosis factor-alpha (TNF-alpha)-mediated NF-kappaB activation.
      TRIP ablation results in early embryonic lethality in mice. To investigate TRIP
      function in epidermis, we examined its expression and the effect of TRIP
      knockdown (KD) in keratinocytes. TRIP mRNA expression was strongly downregulated
      in primary human keratinocytes undergoing differentiation triggered by high cell
      density or high calcium. Short-term phorbol-12-myristate-13-acetate (TPA)
      treatment or inhibition of phosphatidylinositol-3 kinase signaling in
      proliferative keratinocytes suppressed TRIP transcription. Inhibition by TPA was
      protein kinase C dependent. Keratinocytes undergoing KD of TRIP expression by
      lentiviral short-hairpin RNA (shRNA; T4 and T5) had strongly reduced
      proliferation rates compared with control shRNA. Cell cycle analysis demonstrated
      that TRIP-KD caused growth arrest in the G1/S phase. Keratinocytes with TRIP-KD
      resembled differentiated cells consistent with the augmented expression of
      differentiation markers keratin 1 and filaggrin. Luciferase-based reporter assays
      showed no increase in NF-kappaB activity in TRIP-KD keratinocytes, indicating
      that NF-kappaB activity in keratinocytes is not regulated by TRIP. TRIP
      expression was increased by ~2-fold in basal cell carcinomas compared with normal
      skin. These results underline the important role of TRIP in the regulation of
      cell cycle progression and the tight linkage of its expression to keratinocyte
      proliferation.

PMID- 21068753
TI  - Targeting x-linked inhibitor of apoptosis protein for melanoma therapy: the need
      for more homogeneous samples and the importance of cell lines.

PMID- 21068754
TI  - Epidermal FABP (FABP5) regulates keratinocyte differentiation by 13(S)-HODE
      mediated activation of the NF-kappaB signaling pathway.
AB  - Fatty acid-binding proteins (FABPs) are postulated to serve as lipid shuttles
      that solubilize hydrophobic fatty acids and deliver them to appropriate
      intracellular sites. Epidermal FABP (E-FABP/FABP5) is predominantly expressed in
      keratinocytes and is overexpressed in the actively proliferating tissue
      characteristic of psoriasis and wound healing. In this study, we found decreased
      expression of the differentiation-specific proteins keratin 1, involucrin, and
      loricrin in E-FABP(-/-) keratinocytes relative to E-FABP(+/+) keratinocytes. We
      also determined that incorporation of linoleic acid was significantly reduced in
      E-FABP(-/-) keratinocytes. Although linoleic acid did not directly affect
      keratinocyte differentiation, keratin 1 expression was induced by the linoleic
      acid derivative 13(S)-hydroxyoctadecadienoic acid (13(S)-HODE), and this
      induction was concomitant with increased NF-kappaB activity. In E-FABP(-/-)
      keratinocytes, the expression of 13(S)-HODE and the subsequent induction of NF
      kappaB activity was lower than in wild-type keratinocytes. The reduction of
      linoleic acid in E-FABP(-/-) keratinocytes led to decreased cellular 13(S)-HODE
      content, resulting in decreased keratin 1 expression through downregulation of NF
      kappaB activity. The regulation of fatty acid metabolism by E-FABP during
      keratinocyte differentiation suggests that E-FABP may have a role in the
      pathogenesis of psoriasis.

PMID- 21068755
TI  - Irritant-induced migration of Langerhans cells coincides with an IL-10-dependent
      switch to a macrophage-like phenotype.
AB  - Langerhans cells (LCs) migrate after topical exposure of the skin to irritants,
      despite the supposed independence of irritant contact dermatitis from adaptive
      immunity. Whereas allergen-activated LCs are known to migrate to the draining
      lymph nodes (LNs), the fate of migrated LCs upon topical irritant exposure is
      unknown. Here, we identified a phenotypic switch of LCs after their migration
      into the dermis upon irritant exposure. With the aid of ex vivo intact human skin
      and epidermal sheets, we show that dermal fibroblasts are necessary for an IL-10
      dependent postmigrational phenotypic switch of LCs into macrophage-like cells.
      Exposure of ex vivo skin to a panel of seven irritants resulted in a decrease in
      the number of CD1a(+) cells and an increase in CD14(+)/CD68(+) cells in the
      dermis. Neutralizing antibodies against IL-10 totally inhibited the phenotypic LC
      to-macrophage transition, but did not influence the migration of CD1a(+) cells.
      Exposure of epidermal sheets to irritants resulted in a fibroblast-dependent LC
      to-CD14(+)/CD68(+) switch coinciding with migration, which could be totally
      inhibited by neutralizing antibodies against either IL-10 or CCL2/CCL5 (two
      chemokines responsible for epidermal-to-dermal migration). We have thus
      identified an IL-10-dependent phenotypic switch of LCs into macrophage-like cells
      upon irritant exposure and emigration from the epidermis.

PMID- 21068756
TI  - The dermoscopical and histopathological patterns of nevi correlate with the
      frequency of BRAF mutations.

PMID- 21068757
TI  - Axl promotes cutaneous squamous cell carcinoma survival through negative
      regulation of pro-apoptotic Bcl-2 family members.
AB  - Expression of Axl, a receptor tyrosine kinase, is increased in cutaneous squamous
      cell carcinoma (SCC). Examination of a series of cutaneous SCC tumors revealed
      positive phospho-Akt (P-Akt) staining accompanied by weak TUNEL staining in Axl
      positive tumors, suggesting an anti-apoptotic role for Axl in SCC survival. The
      role of Axl in UV-induced apoptosis was investigated in a cutaneous SCC cell line
      using retroviral short hairpin RNA sequences enabling stable Axl knock-down. We
      show that, although Axl knock-down has no effect on cell proliferation, it
      sensitizes cells to UV-induced apoptosis through increased activation of the pro
      apoptotic protein Bad, a change in the conformation of Bax and Bak, release of
      cytochrome c into the cytosol, and activation of caspases. These events are
      accompanied by faster Akt dephosphorylation in UV-treated Axl knock-down cells
      and correlate with the degree of Axl knock-down. Treatment with the pan-caspase
      inhibitor zVAD-fmk partially rescued cells from UV-induced apoptosis but did not
      affect Bid cleavage or cytochrome c release, suggesting that cells die via the
      mitochondrial-mediated pathway. Thus, Axl confers resistance of SCC cells to
      apoptosis and displays potential as a target for therapeutic intervention in
      cutaneous SCC.

PMID- 21068758
TI  - Prostate cancer: HIFU is effective, but associated morbidity still remains
      unclear.

PMID- 21068759
TI  - Bladder cancer: Photodynamic diagnosis can improve surgical outcome.

PMID- 21068760
TI  - Andrology: Identifying late-onset hypogonadism in older men.

PMID- 21068761
TI  - An update on new oral PDE5 inhibitors for the treatment of erectile dysfunction.
AB  - The management of erectile dysfunction (ED) has been revolutionized by the
      discovery of phosphodiesterase 5 (PDE5) inhibitors, which have been commercially
      available for more than a decade and are the first-line therapeutic option for
      men with ED. Sildenafil, vardenafil and tadalafil were approved by the European
      Medicine Agency and the US FDA for the treatment of ED on the back of their high
      efficacy rates and favorable safety profiles. However, despite the fact that more
      than 50 million patients with ED worldwide have been successfully treated with
      one of these PDE5 inhibitors, some men--most notably those with severe neurologic
      damage, diabetes mellitus or severe vascular disease--are resistant to the
      currently available drugs and require more-invasive treatments, such as
      intracavernosal injection therapy. Partly as a consequence of this, research into
      alternative therapeutic approaches continues, including the development of new
      PDE5 inhibitors, centrally acting pharmaceutical agents, and application of
      molecular technologies such as gene therapy and stem cell therapy.

PMID- 21068762
TI  - Serum tumor markers in the evaluation of male germ cell tumors.
AB  - Serum tumor markers play a critical role in the diagnosis, staging, risk
      stratification, and surveillance of patients with testicular germ cell tumors
      (GCTs). Production of the oncofetal substances alpha fetoprotein and human
      chorionic gonadotropin can aid the diagnosis of testicular GCTs, and specific
      patterns of marker elevation can be used to determine the type of tumor,
      particularly as it pertains to nonseminoma. These markers, in addition to lactate
      dehydrogenase, have been incorporated in the standard TNM staging system for
      testicular tumors; the S stage category corresponds to serum elevation of these
      proteins. Furthermore, the degree of serum tumor marker elevation has been
      incorporated into standardized patient risk groupings, which are used to guide
      therapeutic management. The rate of tumor marker decay after radical orchiectomy
      is an important index to monitor, as a slow decline might be indicative of
      metastatic disease and should prompt a thorough systemic survey. The rate of
      tumor marker decline is already being utilized in the setting of metastatic GCTs
      to determine response to chemotherapy, and has been used in some scenarios to
      individualize the type of chemotherapy patients received. Compared to any other
      solid organ malignancy, the role of serum tumor markers in GCT is unprecedented;
      these markers are instrumental in the diagnosis and management of testicular GCT.

PMID- 21068763
TI  - Uterus preservation in pelvic organ prolapse surgery.
AB  - Attitudes to sexuality and the psychological value of reproductive organs have
      changed in Western countries over the last few decades. Nevertheless, repair of
      pelvic support defects with concomitant hysterectomy is still considered the
      standard treatment for pelvic organ prolapse. Over the last 10 years, however,
      interest has been growing in uterus-sparing surgery, which can be divided into
      vaginal, abdominal, and laparoscopic procedures. The majority of studies on
      uterus-sparing surgery, with the exception of abdominal techniques, report few
      cases with short follow-up. Sacrospinous hysteropexy is the most studied vaginal
      technique for uterus preservation and favorable results have been demonstrated,
      although the majority of studies are flawed by selection and information bias,
      short follow-up and lack of adequate control groups. Abdominal and laparoscopic
      procedures are promising, providing similar functional and anatomical results to
      hysterectomy and sacrocolpopexy. Consensus is growing that the uterus can be
      preserved at the time of pelvic reconstructive surgery in appropriately selected
      women who desire it. The results of comparison trials and prospective studies
      confirm that uterus-sparing surgery is feasible and is associated with similar
      outcomes to hysterectomy, as well as shorter operating times. Surgeons should be
      ready to respond to the wishes of female patients who want to preserve vaginal
      function and the uterus.

PMID- 21068764
TI  - Unilateral adrenalectomy improves urinary protein excretion but does not abolish
      its relationship to sodium excretion in patients with aldosterone-producing
      adenoma.
AB  - Experimental and human data suggest that adverse cardiovascular (CV) and renal
      effects of aldosterone excess are dependent on concomitant dietary salt intake.
      Increased urinary protein (Uprot) is an early sign of nephropathy independently
      associated with CV risk. We have previously reported a positive association
      between Uprot and urinary sodium (UNa) in patients with hyperaldosteronism, but
      not in patients with normal aldosterone levels. We aimed to determine whether
      Uprot is related to UNa in patients with aldosterone-producing adenoma (APA) and
      whether the degree of Uprot and strength of this relationship is reduced
      following correction of hyperaldosteronism. Subjects with APA (n=24) underwent
      measurement of 24 h Uprot and UNa before and after unilateral adrenalectomy
      (follow-up 15.0+/-11.9 months). Following surgery, mean clinic systolic blood
      pressure fell (150.4+/-18.2 vs 134.5+/-14.5 mm Hg, P=0.0008), despite a reduction
      in number of antihypertensive medications, and Uprot (211.2+/-101.6 vs 106.0+/
      41.8 mg per day, P<0.0001) decreased. There was a positive correlation between
      Uprot and UNa both before (r=0.5477, P=0.0056) and after (r=0.5097, P=0.0109)
      adrenalectomy. Changes in UNa independently predicted Uprot reduction (P=0.0189).
      These findings suggest that both aldosterone levels and dietary salt contribute
      to renal damage, and that once glomerular damage occurs it is not completely
      resolved following correction of hyperaldosteronism. Our study suggests that
      treatment strategies based on reduction of aldosterone effects, by adrenalectomy
      or mineralocorticoid receptor blockade, in conjunction with low-salt diet would
      provide additional target-organ protection in patients with primary
      aldosteronism.

PMID- 21068765
TI  - Hemodynamic variables during exercise in childhood and resting systolic blood
      pressure levels 6 years later in adolescence: the European Youth Heart Study.
AB  - The aim of this study was to analyze whether systolic blood pressure (SBP), heart
      rate (HR) and rate pressure product (RPP) during exercise in childhood can
      predict resting SBP levels in adolescence independent of resting SBP and
      conventional cardiovascular risk factors. We studied this in a sample of Danish
      children followed longitudinally for 6 years. The study comprised 226 children
      randomly sampled at age 9, who had their blood pressure and HR measured during
      ergometer exercise to exhaustion and was reassessed in adolescence. SBP and RPP
      during exercise in stage two of the test were positively associated with future
      resting SBP, independent of resting SBP in childhood (P=0.045 and P=0.013,
      respectively). After additional adjustment for conventional cardiovascular risk
      factors the associations with SBP and RPP during stage two on future resting SBP
      only slightly materially change, although only RPP remained significant (P=0.059
      and P=0.012, respectively). No significant independent associations were observed
      for HR during exercise, but associations were in the same direction. Our results
      supports that measuring SBP and RPP, during a standard acute ergometer exercise
      test in children, improves the prediction of future SBP levels during rest in
      adolescence independent of resting SBP and conventional cardiovascular risk
      factors.

PMID- 21068767
TI  - Cell migration: a new move for SUMO.

PMID- 21068768
TI  - Gene expression: Patterning by piRNAs.

PMID- 21068766
TI  - Neuronal circuitry for pain processing in the dorsal horn.
AB  - Neurons in the spinal dorsal horn process sensory information, which is then
      transmitted to several brain regions, including those responsible for pain
      perception. The dorsal horn provides numerous potential targets for the
      development of novel analgesics and is thought to undergo changes that contribute
      to the exaggerated pain felt after nerve injury and inflammation. Despite its
      obvious importance, we still know little about the neuronal circuits that process
      sensory information, mainly because of the heterogeneity of the various neuronal
      components that make up these circuits. Recent studies have begun to shed light
      on the neuronal organization and circuitry of this complex region.

PMID- 21068769
TI  - Cytoskeleton: Keeping minus ends stable.

PMID- 21068770
TI  - Angiographic and OCT features of retinal angiomatous proliferation.
AB  - BACKGROUND: To propose a classification system for retinal angiomatous
      proliferation (RAP) on the basis of the indocyanine green angiography (ICG).
      METHODS: Retrospective chart review of 55 eyes of 55 patients presenting with
      RAP. Fluorescein angiography (FA), ICG and optical coherence tomography (OCT)
      were used to evaluate the patients. RESULTS: All RAP lesions appeared as occult
      or minimally classic CNV on FA without clear evidence of pigment epithelium
      detachment (PED). We were able to identify five different patterns of RAP on the
      basis of ICG. These were focal (27.2%), irregular (21.8%), circular (21.8%),
      multifocal (18.2%), and combined (10.9%) hyperfluorescence. The sudden
      termination of retinal vessel course sign was observed in 14 of 55 eyes (25.4%),
      which had a circular or irregular pattern on the ICG. Only the circular RAP
      exhibited a late hypofluorescence ('wash out') with staining of the surrounding
      tissue on the ICG. Forty eight of 55 eyes (86%) had PED according to the OCT. Out
      of these 48 eyes, 19 had intraretinal fluid (IRF) alone, and the rest had IRF and
      subretinal fluid. The eight eyes (14%) without PED belonged to the focal
      hyperfluorescence group and the fluid was located intraretinally in cystic
      spaces. In addition, in four eyes (7%) with coexisting CNV a band of tissue
      beneath the RAP protruding in the PED was observed. CONCLUSION: We propose a
      classification system for RAP on the basis of ICG and present the angiographic
      and OCT findings of these lesions. These data may further aid in the early
      diagnosis of RAP and can be also used for prognosis and clinical course
      documentation.

PMID- 21068774
TI  - Environmental proteomics of microbial plankton in a highly productive coastal
      upwelling system.
AB  - Metaproteomics is one of a suite of new approaches providing insights into the
      activities of microorganisms in natural environments. Proteins, the final
      products of gene expression, indicate cellular priorities, taking into account
      both transcriptional and posttranscriptional control mechanisms that control
      adaptive responses. Here, we report the proteomic composition of the < 1.2 MUm
      fraction of a microbial community from Oregon coast summer surface waters,
      detected with two-dimensional liquid chromatography coupled with electrospray
      tandem mass spectrometry. Spectra corresponding to proteins involved in protein
      folding and biosynthesis, transport, and viral capsid structure were the most
      frequently detected. A total of 36% of all the detected proteins were best
      matches to the SAR11 clade, and other abundant coastal microbial clades were also
      well represented, including the Roseobacter clade (17%), oligotrophic marine
      gammaproteobacteria group (6%), OM43 clade (1%). Viral origins were attributed to
      2.5% of proteins. In contrast to oligotrophic waters, phosphate transporters were
      not highly detected in this nutrient-rich system. However, transporters for amino
      acids, taurine, polyamines and glutamine synthetase were among the most highly
      detected proteins, supporting predictions that carbon and nitrogen are more
      limiting than phosphate in this environment. Intriguingly, one of the highly
      detected proteins was methanol dehydrogenase originating from the OM43 clade,
      providing further support for recent reports that the metabolism of one-carbon
      compounds by these streamlined methylotrophs might be an important feature of
      coastal ocean biogeochemistry.

PMID- 21068775
TI  - Microbial methanol uptake in northeast Atlantic waters.
AB  - Methanol is the predominant oxygenated volatile organic compound in the
      troposphere, where it can significantly influence the oxidising capacity of the
      atmosphere. However, we do not understand which processes control oceanic
      concentrations, and hence, whether the oceans are a source or a sink to the
      atmosphere. We report the first methanol loss rates in seawater by demonstrating
      that (14)C-labelled methanol can be used to determine microbial uptake into
      particulate biomass, and oxidation to (14)CO(2). We have found that methanol is
      used predominantly as a microbial energy source, but also demonstrated its use as
      a carbon source. We report biological methanol oxidation rates between 2.1 and
      8.4  nmol l(-1) day(-1) in surface seawater of the northeast Atlantic. Kinetic
      experiments predict a V(max) of up to 29  nmol l(-1) day(-1), with a high
      affinity K(m) constant of 9.3  nM in more productive coastal waters. We report
      surface concentrations of methanol in the western English channel of 97+/-8  nM
      (n=4) between May and June 2010, and for the wider temperate North Atlantic
      waters of 70+/-13  nM (n=6). The biological turnover time of methanol has been
      estimated between 7 and 33 days, although kinetic experiments suggest a 7-day
      turnover in more productive shelf waters. Methanol uptake rates into microbial
      particles significantly correlated with bacterial and phytoplankton parameters,
      suggesting that it could be used as a carbon source by some bacteria and possibly
      some mixotrophic eukaryotes. Our results provide the first methanol loss rates
      from seawater, which will improve the understanding of the global methanol
      budget.

PMID- 21068776
TI  - Correlating carbon monoxide oxidation with cox genes in the abundant Marine
      Roseobacter Clade.
AB  - The Marine Roseobacter Clade (MRC) is a numerically and biogeochemically
      significant component of the bacterioplankton. Annotation of multiple MRC genomes
      has revealed that an abundance of carbon monoxide dehydrogenase (CODH) cox genes
      are present, subsequently implying a role for the MRC in marine CO cycling. The
      cox genes fall into two distinct forms based on sequence analysis of the coxL
      gene; forms I and II. The two forms are unevenly distributed across the MRC
      genomes. Most (18/29) of the MRC genomes contain only the putative form II coxL
      gene. Only 10 of the 29 MRC genomes analysed have both the putative form II and
      the definitive form I coxL. None have only the form I coxL. Genes previously
      shown to be required for post-translational maturation of the form I CODH enzyme
      are absent from the MRC genomes containing only form II. Subsequent analyses of a
      subset of nine MRC strains revealed that only MRC strains with both coxL forms
      are able to oxidise CO.

PMID- 21068778
TI  - Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients
      with metastatic renal cell cancer: a clinical phase-I study.
AB  - Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC)
      remains poor, and experimental therapeutic strategies are warranted. Transfection
      of tumor cells with co-stimulatory molecules and/or cytokines is able to increase
      immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen
      (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic
      clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 * 10(6)
      interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells
      (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological
      and clinical responses. Vaccination was feasible and safe. In all, 50% of the
      patients showed stable disease throughout the study; the median time to
      progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80
      tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine
      profile with increasing amounts of antigen-specific IL-10 secretion was observed
      in most of the responding patients. Interferon-gamma secretion by patient
      lymphocytes upon antigen-specific and non-specific stimulation was substantially
      impaired, both before and during vaccination, as compared with healthy controls.
      This is possibly due to profound tumor-induced immunosuppression, which may
      prevent induction of antitumor immune responses by the gene-modified vaccine.
      Vaccination in minimal residual disease with concurrent depletion of regulatory
      cells might be one strategy to overcome this limitation.

PMID- 21068779
TI  - 10-year stability of clinical-grade serum-free gamma-retroviral vector-containing
      medium.
AB  - More than 10 years ago, we developed an efficient protocol for serum-free
      retroviral transduction of human hematopoietic stem cells derived from mobilized
      peripheral blood. After upscaling of the methodology, serum-free retroviral
      gibbon-ape leukemia virus (GALV) pseudotype PG13/LN vector supernatant produced
      under strict good manufacturing practice (GMP) conditions was used in the first
      clinical gene-marking trial in Germany. In this study, we analyzed the titer and
      transduction efficiency of this serum-free clinical-grade retroviral supernatant
      10 years after production to evaluate the long-term stability. Long-term storage
      and transport on dry ice resulted in modestly decreased titers and levels of
      transduction efficiency in CD34+ cells ranging from 38.4 to 49.1%. We conclude
      that the stability of retroviral vectors in serum-free medium allows extended
      storage and distribution of approved clinical-grade retroviral vector stocks to
      distant sites in multicenter clinical trials.

PMID- 21068780
TI  - Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in
      inflammatory bone loss.
AB  - Alveolar bone loss associated with periodontal diseases is the result of
      osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein
      kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune
      response as a key phosphatase capable of dephosphorylating activated MAPKs. In
      this study, rat macrophages transduced with recombinant adenovirus (Ad.)MKP-1
      specifically dephosphorylated activated MAPKs induced by lipopolysaccharide (LPS)
      compared with control cells. Bone marrow macrophages from MKP-1 knockout (KO)
      mice exhibited higher interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)
      alpha, and select chemokine compared with wild-type (WT) mice when stimulated by
      LPS. In addition, bone marrow cultures from MKP-1 KO mice exhibited significantly
      more osteoclastogenesis induced by LPS than when compared with WT mice.
      Importantly, MKP-1 gene transfer in bone marrow cells of MKP-1 KO mice
      significantly decreased IL-6, IL-10, TNF-alpha and chemokine levels, and formed
      fewer osteoclasts induced by LPS than compared with control group of cells.
      Furthermore, MKP-1 gene transfer in an experimental periodontal disease model
      attenuated bone resorption induced by LPS. Histological analysis confirmed that
      periodontal tissues transduced with Ad. MKP-1 exhibited less infiltrated
      inflammatory cells, less osteoclasts and less IL-6 than compared with rats of
      control groups. These studies indicate that MKP-1 is a key therapeutic target to
      control of inflammation-induced bone loss.

PMID- 21068782
TI  - States or the union.

PMID- 21068781
TI  - CD20-targeted measles virus shows high oncolytic specificity in clinical samples
      from lymphoma patients independent of prior rituximab therapy.
AB  - New therapeutic modalities for B-cell non-Hodgkin's lymphomas (B-NHL) are needed,
      especially for relapsing and aggressive subtypes. Toward this end, we previously
      generated a fully CD20-targeted and armed measles virus, and tested its efficacy
      in a xenograft model of mantle cell lymphoma (MCL). Here, we quantify its spread
      in peripheral blood mononuclear cells and/or tissue of patients with different
      histological subtypes of B-NHL, including splenic marginal zone lymphoma (SMZL).
      CD20-targeted MV efficiently infects lymphoma cells from SMZL and MCL while
      sparing most cells in the CD20-negative population, in contrast to the parental
      vaccine-lineage MV, which infects CD20-positive and CD20-negative cells equally.
      Rituximab therapy (4-8 months before relapse) did not interfere with the
      infectivity and specificity of MV(green)H(blind)antiCD20 in patient lymphoma
      samples. Thus, CD20-targeted oncolytic virotherapy is likely to be effective
      after previous antiCD20 therapy.

PMID- 21068783
TI  - Combating schizophrenia.

PMID- 21068784
TI  - Worth waiting for.

PMID- 21068785
TI  - Double trouble? To throw cash at science is a mistake.

PMID- 21068796
TI  - Measuring the meltdown.

PMID- 21068797
TI  - Vaccine offers meningitis hope.

PMID- 21068798
TI  - China tackles surge in mental illness.

PMID- 21068799
TI  - US science faces a squeeze.

PMID- 21068800
TI  - Funding crisis hits US ageing research.

PMID- 21068802
TI  - There will be blood.

PMID- 21068803
TI  - Schizophrenia: The making of a troubled mind.

PMID- 21068804
TI  - Schizophrenia: The drug deadlock.

PMID- 21068805
TI  - Neuroscience: Settling the great glia debate.

PMID- 21068806
TI  - Short-lived campaigns are not enough.

PMID- 21068807
TI  - Cognitive remediation therapy needs funding.

PMID- 21068812
TI  - Concrete helix recalls smallpox win.

PMID- 21068813
TI  - Water: act now to restore river health.

PMID- 21068814
TI  - Cities need plants and animals too.

PMID- 21068815
TI  - Water: biofuels sap supplies.

PMID- 21068817
TI  - John Huchra (1948-2010).

PMID- 21068816
TI  - Ireland should fund best research.

PMID- 21068818
TI  - Stroke: recovery inhibitors under attack.

PMID- 21068819
TI  - Electronics: A diverse printed future.

PMID- 21068820
TI  - Neuroscience: the split view of motion.

PMID- 21068821
TI  - Animal behaviour: How to confuse thirsty bats.

PMID- 21068822
TI  - Fundamental constants: Big G revisited.

PMID- 21068824
TI  - Evolutionary genomics: When abnormality is beneficial.

PMID- 21068825
TI  - High-temperature superconductivity: Mind the pseudogap.

PMID- 21068826
TI  - Rethinking schizophrenia.
AB  - How will we view schizophrenia in 2030? Schizophrenia today is a chronic,
      frequently disabling mental disorder that affects about one per cent of the
      world's population. After a century of studying schizophrenia, the cause of the
      disorder remains unknown. Treatments, especially pharmacological treatments, have
      been in wide use for nearly half a century, yet there is little evidence that
      these treatments have substantially improved outcomes for most people with
      schizophrenia. These current unsatisfactory outcomes may change as we approach
      schizophrenia as a neurodevelopmental disorder with psychosis as a late,
      potentially preventable stage of the illness. This 'rethinking' of schizophrenia
      as a neurodevelopmental disorder, which is profoundly different from the way we
      have seen this illness for the past century, yields new hope for prevention and
      cure over the next two decades.

PMID- 21068827
TI  - From maps to mechanisms through neuroimaging of schizophrenia.
AB  - Functional and structural brain imaging has identified neural and
      neurotransmitter systems involved in schizophrenia and their link to cognitive
      and behavioural disturbances such as psychosis. Mapping such abnormalities in
      patients, however, cannot fully capture the strong neurodevelopmental component
      of schizophrenia that pre-dates manifest illness. A recent strategy to address
      this issue has been to focus on mechanisms of disease risk. Imaging genetics
      techniques have made it possible to define neural systems that mediate heritable
      risk linked to candidate and genome-wide-supported common variants, and
      mechanisms for environmental risk and gene-environment interactions are emerging.
      Characterizing the neural risk architecture of schizophrenia provides a
      translational research strategy for future treatments.

PMID- 21068828
TI  - The environment and schizophrenia.
AB  - Psychotic syndromes can be understood as disorders of adaptation to social
      context. Although heritability is often emphasized, onset is associated with
      environmental factors such as early life adversity, growing up in an urban
      environment, minority group position and cannabis use, suggesting that exposure
      may have an impact on the developing 'social' brain during sensitive periods.
      Therefore heritability, as an index of genetic influence, may be of limited
      explanatory power unless viewed in the context of interaction with social
      effects. Longitudinal research is needed to uncover gene-environment interplay
      that determines how expression of vulnerability in the general population may
      give rise to more severe psychopathology.

PMID- 21068829
TI  - Glia.

PMID- 21068830
TI  - Developmental genetics of vertebrate glial-cell specification.
AB  - Oligodendrocytes and astrocytes are macroglial cells of the vertebrate central
      nervous system. These cells have diverse roles in the maintenance of neurological
      function. In the embryo, the genetic mechanisms that underlie the specification
      of macroglial precursors in vivo appear strikingly similar to those that regulate
      the development of the diverse neuron types. The switch from producing neuronal
      to glial subtype-specific precursors can be modelled as an interplay between
      region-restricted components and temporal regulators that determine neurogenic or
      gliogenic phases of development, contributing to glial diversity. Gaining insight
      into the developmental genetics of macroglia has great potential to improve our
      understanding of a variety of neurological disorders in humans.

PMID- 21068831
TI  - Regulation of synaptic connectivity by glia.
AB  - The human brain contains more than 100 trillion (10(14)) synaptic connections,
      which form all of its neural circuits. Neuroscientists have long been interested
      in how this complex synaptic web is weaved during development and remodelled
      during learning and disease. Recent studies have uncovered that glial cells are
      important regulators of synaptic connectivity. These cells are far more active
      than was previously thought and are powerful controllers of synapse formation,
      function, plasticity and elimination, both in health and disease. Understanding
      how signalling between glia and neurons regulates synaptic development will offer
      new insight into how the nervous system works and provide new targets for the
      treatment of neurological diseases.

PMID- 21068832
TI  - Glial and neuronal control of brain blood flow.
AB  - Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how
      these cells control blood flow is crucial for understanding how neural
      computation is powered, for interpreting functional imaging scans of brains, and
      for developing treatments for neurological disorders. It is now recognized that
      neurotransmitter-mediated signalling has a key role in regulating cerebral blood
      flow, that much of this control is mediated by astrocytes, that oxygen modulates
      blood flow regulation, and that blood flow may be controlled by capillaries as
      well as by arterioles. These conceptual shifts in our understanding of cerebral
      blood flow control have important implications for the development of new
      therapeutic approaches.

PMID- 21068833
TI  - Myelination and support of axonal integrity by glia.
AB  - The myelination of axons by glial cells was the last major step in the evolution
      of cells in the vertebrate nervous system, and white-matter tracts are key to the
      architecture of the mammalian brain. Cell biology and mouse genetics have
      provided insight into axon-glia signalling and the molecular architecture of the
      myelin sheath. Glial cells that myelinate axons were found to have a dual role by
      also supporting the long-term integrity of those axons. This function may be
      independent of myelin itself. Myelin abnormalities cause a number of neurological
      diseases, and may also contribute to complex neuropsychiatric disorders.

PMID- 21068834
TI  - The myeloid cells of the central nervous system parenchyma.
AB  - A microglial cell is both a glial cell of the central nervous system and a
      mononuclear phagocyte, which belongs to the haematopoietic system and is involved
      in inflammatory and immune responses. As such, microglia face a challenging task.
      The neurons of the central nervous system cannot divide and be replenished, and
      therefore need to be protected against pathogens, which is a key role of the
      immune system, but without collateral damage. In addition, after physical injury,
      neural cells need restorative support, which is provided by inflammatory
      responses. Excessive or chronic inflammatory responses can, however, be harmful.
      How microglia balance these demands, and how their behaviour can be modified to
      ameliorate disorders of the central nervous system, is becoming clear.

PMID- 21068835
TI  - Dysfunction in GABA signalling mediates autism-like stereotypies and Rett
      syndrome phenotypes.
AB  - Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator
      methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several
      neurodevelopmental disorders including cognitive disorders, autism, juvenile
      onset schizophrenia and encephalopathy with early lethality. Rett syndrome is
      characterized by apparently normal early development followed by regression,
      motor abnormalities, seizures and features of autism, especially stereotyped
      behaviours. The mechanisms mediating these features are poorly understood. Here
      we show that mice lacking Mecp2 from GABA (gamma-aminobutyric acid)-releasing
      neurons recapitulate numerous Rett syndrome and autistic features, including
      repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons
      also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic
      neurons show reduced inhibitory quantal size, consistent with a presynaptic
      reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase
      2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is
      critical for normal function of GABA-releasing neurons and that subtle
      dysfunction of GABAergic neurons contributes to numerous neuropsychiatric
      phenotypes.

PMID- 21068836
TI  - Genetic dissection of an amygdala microcircuit that gates conditioned fear.
AB  - The role of different amygdala nuclei (neuroanatomical subdivisions) in
      processing Pavlovian conditioned fear has been studied extensively, but the
      function of the heterogeneous neuronal subtypes within these nuclei remains
      poorly understood. Here we use molecular genetic approaches to map the functional
      connectivity of a subpopulation of GABA-containing neurons, located in the
      lateral subdivision of the central amygdala (CEl), which express protein kinase C
      delta (PKC-delta). Channelrhodopsin-2-assisted circuit mapping in amygdala slices
      and cell-specific viral tracing indicate that PKC-delta(+) neurons inhibit output
      neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory
      synapses with PKC-delta(-) neurons in CEl. Electrical silencing of PKC-delta(+)
      neurons in vivo suggests that they correspond to physiologically identified units
      that are inhibited by the conditioned stimulus, called CEl(off) units. This
      correspondence, together with behavioural data, defines an inhibitory
      microcircuit in CEl that gates CEm output to control the level of conditioned
      freezing.

PMID- 21068838
TI  - Hidden magnetic excitation in the pseudogap phase of a high-T(c) superconductor.
AB  - The elucidation of the pseudogap phenomenon of the high-transition-temperature
      (high-T(c)) copper oxides-a set of anomalous physical properties below the
      characteristic temperature T* and above T(c)-has been a major challenge in
      condensed matter physics for the past two decades. Following initial indications
      of broken time-reversal symmetry in photoemission experiments, recent polarized
      neutron diffraction work demonstrated the universal existence of an unusual
      magnetic order below T* (refs 3, 4). These findings have the profound implication
      that the pseudogap regime constitutes a genuine new phase of matter rather than a
      mere crossover phenomenon. They are furthermore consistent with a particular type
      of order involving circulating orbital currents, and with the notion that the
      phase diagram is controlled by a quantum critical point. Here we report inelastic
      neutron scattering results for HgBa(2)CuO(4+delta) that reveal a fundamental
      collective magnetic mode associated with the unusual order, and which further
      support this picture. The mode's intensity rises below the same temperature T*
      and its dispersion is weak, as expected for an Ising-like order parameter. Its
      energy of 52-56 meV renders it a new candidate for the hitherto unexplained
      ubiquitous electron-boson coupling features observed in spectroscopic studies.

PMID- 21068837
TI  - Encoding of conditioned fear in central amygdala inhibitory circuits.
AB  - The central amygdala (CEA), a nucleus predominantly composed of GABAergic
      inhibitory neurons, is essential for fear conditioning. How the acquisition and
      expression of conditioned fear are encoded within CEA inhibitory circuits is not
      understood. Using in vivo electrophysiological, optogenetic and pharmacological
      approaches in mice, we show that neuronal activity in the lateral subdivision of
      the central amygdala (CEl) is required for fear acquisition, whereas conditioned
      fear responses are driven by output neurons in the medial subdivision (CEm).
      Functional circuit analysis revealed that inhibitory CEA microcircuits are highly
      organized and that cell-type-specific plasticity of phasic and tonic activity in
      the CEl to CEm pathway may gate fear expression and regulate fear generalization.
      Our results define the functional architecture of CEA microcircuits and their
      role in the acquisition and regulation of conditioned fear behaviour.

PMID- 21068839
TI  - Ultrathin compound semiconductor on insulator layers for high-performance
      nanoscale transistors.
AB  - Over the past several years, the inherent scaling limitations of silicon (Si)
      electron devices have fuelled the exploration of alternative semiconductors, with
      high carrier mobility, to further enhance device performance. In particular,
      compound semiconductors heterogeneously integrated on Si substrates have been
      actively studied: such devices combine the high mobility of III-V semiconductors
      and the well established, low-cost processing of Si technology. This integration,
      however, presents significant challenges. Conventionally, heteroepitaxial growth
      of complex multilayers on Si has been explored-but besides complexity, high
      defect densities and junction leakage currents present limitations in this
      approach. Motivated by this challenge, here we use an epitaxial transfer method
      for the integration of ultrathin layers of single-crystal InAs on Si/SiO(2)
      substrates. As a parallel with silicon-on-insulator (SOI) technology, we use
      'XOI' to represent our compound semiconductor-on-insulator platform. Through
      experiments and simulation, the electrical properties of InAs XOI transistors are
      explored, elucidating the critical role of quantum confinement in the transport
      properties of ultrathin XOI layers. Importantly, a high-quality InAs/dielectric
      interface is obtained by the use of a novel thermally grown interfacial InAsO(x)
      layer (~1 nm thick). The fabricated field-effect transistors exhibit a peak
      transconductance of ~1.6 mS um(-1) at a drain-source voltage of 0.5 V, with an
      on/off current ratio of greater than 10,000.

PMID- 21068840
TI  - Early oxygenation of the terrestrial environment during the Mesoproterozoic.
AB  - Geochemical data from ancient sedimentary successions provide evidence for the
      progressive evolution of Earth's atmosphere and oceans. Key stages in increasing
      oxygenation are postulated for the Palaeoproterozoic era (~2.3 billion years ago,
      Gyr ago) and the late Proterozoic eon (about 0.8 Gyr ago), with the latter
      implicated in the subsequent metazoan evolutionary expansion. In support of this
      rise in oxygen concentrations, a large database shows a marked change in the
      bacterially mediated fractionation of seawater sulphate to sulphide of Delta(34)S
      < 250/00 before 1 Gyr to >=500/00 after 0.64 Gyr. This change in Delta(34)S has
      been interpreted to represent the evolution from single-step bacterial sulphate
      reduction to a combination of bacterial sulphate reduction and sulphide
      oxidation, largely bacterially mediated. This evolution is seen as marking the
      rise in atmospheric oxygen concentrations and the evolution of non-photosynthetic
      sulphide-oxidizing bacteria. Here we report Delta(34)S values exceeding 500/00
      from a terrestrial Mesoproterozoic (1.18 Gyr old) succession in Scotland, a time
      period that is at present poorly characterized. This level of fractionation
      implies disproportionation in the sulphur cycle, probably involving sulphide
      oxidizing bacteria, that is not evident from Delta(34)S data in the marine
      record. Disproportionation in both red beds and lacustrine black shales at our
      study site suggests that the Mesoproterozoic terrestrial environment was
      sufficiently oxygenated to support a biota that was adapted to an oxygen-rich
      atmosphere, but had also penetrated into subsurface sediment.

PMID- 21068841
TI  - ON and OFF pathways in Drosophila motion vision.
AB  - Motion vision is a major function of all visual systems, yet the underlying
      neural mechanisms and circuits are still elusive. In the lamina, the first optic
      neuropile of Drosophila melanogaster, photoreceptor signals split into five
      parallel pathways, L1-L5. Here we examine how these pathways contribute to visual
      motion detection by combining genetic block and reconstitution of neural activity
      in different lamina cell types with whole-cell recordings from downstream motion
      sensitive neurons. We find reduced responses to moving gratings if L1 or L2 is
      blocked; however, reconstitution of photoreceptor input to only L1 or L2 results
      in wild-type responses. Thus, the first experiment indicates the necessity of
      both pathways, whereas the second indicates sufficiency of each single pathway.
      This contradiction can be explained by electrical coupling between L1 and L2,
      allowing for activation of both pathways even when only one of them receives
      photoreceptor input. A fundamental difference between the L1 pathway and the L2
      pathway is uncovered when blocking L1 or L2 output while presenting moving edges
      of positive (ON) or negative (OFF) contrast polarity: blocking L1 eliminates the
      response to moving ON edges, whereas blocking L2 eliminates the response to
      moving OFF edges. Thus, similar to the segregation of photoreceptor signals in ON
      and OFF bipolar cell pathways in the vertebrate retina, photoreceptor signals
      segregate into ON-L1 and OFF-L2 channels in the lamina of Drosophila.

PMID- 21068842
TI  - Inductive angiocrine signals from sinusoidal endothelium are required for liver
      regeneration.
AB  - During embryogenesis, endothelial cells induce organogenesis before the
      development of circulation. These findings suggest that endothelial cells not
      only form passive conduits to deliver nutrients and oxygen, but also establish an
      instructive vascular niche, which through elaboration of paracrine trophogens
      stimulates organ regeneration, in a manner similar to endothelial-cell-derived
      angiocrine factors that support haematopoiesis. However, the precise mechanism by
      which tissue-specific subsets of endothelial cells promote organogenesis in
      adults is unknown. Here we demonstrate that liver sinusoidal endothelial cells
      (LSECs) constitute a unique population of phenotypically and functionally defined
      VEGFR3(+)CD34(-)VEGFR2(+)VE-cadherin(+)FactorVIII(+)CD45(-) endothelial cells,
      which through the release of angiocrine trophogens initiate and sustain liver
      regeneration induced by 70% partial hepatectomy. After partial hepatectomy,
      residual liver vasculature remains intact without experiencing hypoxia or
      structural damage, which allows study of physiological liver regeneration. Using
      this model, we show that inducible genetic ablation of vascular endothelial
      growth factor (VEGF)-A receptor-2 (VEGFR2) in the LSECs impairs the initial burst
      of hepatocyte proliferation (days 1-3 after partial hepatectomy) and subsequent
      reconstitution of the hepatovascular mass (days 4-8 after partial hepatectomy) by
      inhibiting upregulation of the endothelial-cell-specific transcription factor
      Id1. Accordingly, Id1-deficient mice also manifest defects throughout liver
      regeneration, owing to diminished expression of LSEC-derived angiocrine factors,
      including hepatocyte growth factor (HGF) and Wnt2. Notably, in in vitro co
      cultures, VEGFR2-Id1 activation in LSECs stimulates hepatocyte proliferation.
      Indeed, intrasplenic transplantation of Id1(+/+) or Id1(-/-) LSECs transduced
      with Wnt2 and HGF (Id1(-/-)Wnt2(+)HGF(+) LSECs) re-establishes an inductive
      vascular niche in the liver sinusoids of the Id1(-/-) mice, initiating and
      restoring hepatovascular regeneration. Therefore, in the early phases of
      physiological liver regeneration, VEGFR2-Id1-mediated inductive angiogenesis in
      LSECs through release of angiocrine factors Wnt2 and HGF provokes hepatic
      proliferation. Subsequently, VEGFR2-Id1-dependent proliferative angiogenesis
      reconstitutes liver mass. Therapeutic co-transplantation of inductive
      VEGFR2(+)Id1(+)Wnt2(+)HGF(+) LSECs with hepatocytes provides an effective
      strategy to achieve durable liver regeneration.

PMID- 21068847
TI  - Design of a single-polarization single-mode photonic crystal fiber with a near
      Gaussian mode field and wide bandwidth.
AB  - Single-polarization single-mode (SPSM) fiber can efficiently eliminate
      polarization mode coupling, polarization mode dispersion, and polarization
      dependent loss. Up to now, most single-polarization fibers have been designed
      based on form birefringence, which would result in a non-Gaussian field
      distribution and a small effective mode field area. In this paper, a novel
      structure of SPSM photonic crystal fibers based on the resonant coupling
      phenomena is proposed and analyzed by using a full-vector finite-element method
      with a second-order transparent boundary condition. From the numerical results it
      is confirmed that this fiber has a near-Gaussian mode field within the wavelength
      range from 1.46 to 2.2 MUm, where only one polarized mode exists effectively, and
      the mode field area is about 79 MUm(2) at the wavelength of 1.55 MUm, matching
      that of the conventional single-mode fiber.

PMID- 21068843
TI  - The mechanism of retroviral integration from X-ray structures of its key
      intermediates.
AB  - To establish productive infection, a retrovirus must insert a DNA replica of its
      genome into host cell chromosomal DNA. This process is operated by the intasome,
      a nucleoprotein complex composed of an integrase tetramer (IN) assembled on the
      viral DNA ends. The intasome engages chromosomal DNA within a target capture
      complex to carry out strand transfer, irreversibly joining the viral and cellular
      DNA molecules. Although several intasome/transpososome structures from the DDE(D)
      recombinase superfamily have been reported, the mechanics of target DNA capture
      and strand transfer by these enzymes remained unclear. Here we report crystal
      structures of the intasome from prototype foamy virus in complex with target DNA,
      elucidating the pre-integration target DNA capture and post-catalytic strand
      transfer intermediates of the retroviral integration process. The cleft between
      IN dimers within the intasome accommodates chromosomal DNA in a severely bent
      conformation, allowing widely spaced IN active sites to access the scissile
      phosphodiester bonds. Our results resolve the structural basis for retroviral DNA
      integration and provide a framework for the design of INs with altered target
      sequences.

PMID- 21068848
TI  - Active optics null test system based on a liquid crystal programmable spatial
      light modulator.
AB  - We present an active null test system adapted to test lenses and wavefronts with
      complex shapes and strong local deformations. This system provides greater
      flexibility than conventional static null tests that match only a precisely
      positioned, individual wavefront. The system is based on a cylindrical Shack
      Hartmann wavefront sensor, a commercial liquid crystal programmable phase
      modulator (PPM), which acts as the active null corrector, enabling the
      compensation of large strokes with high fidelity in a single iteration, and a
      spatial filter to remove unmodulated light when steep phase changes are
      compensated. We have evaluated the PPM's phase response at 635 nm and checked its
      performance by measuring its capability to generate different amounts of defocus
      aberration, finding root mean squared errors below lambda/18 for spherical
      wavefronts with peak-to-valley heights of up to 78.7lambda, which stands as the
      limit from which diffractive artifacts created by the PPM have been found to be
      critical under no spatial filtering. Results of a null test for a complex lens
      (an ophthalmic customized progressive addition lens) are presented and discussed.

PMID- 21068844
TI  - Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase.
AB  - Mononuclear iron-containing oxygenases conduct a diverse variety of oxidation
      functions in biology, including the oxidative demethylation of methylated nucleic
      acids and histones. Escherichia coli AlkB is the first such enzyme that was
      discovered to repair methylated nucleic acids, which are otherwise cytotoxic
      and/or mutagenic. AlkB human homologues are known to play pivotal roles in
      various processes. Here we present structural characterization of oxidation
      intermediates for these demethylases. Using a chemical cross-linking strategy,
      complexes of AlkB-double stranded DNA (dsDNA) containing 1,N(6)-etheno adenine
      (epsilonA), N(3)-methyl thymine (3-meT) and N(3)-methyl cytosine (3-meC) are
      stabilized and crystallized, respectively. Exposing these crystals, grown under
      anaerobic conditions containing iron(II) and alpha-ketoglutarate (alphaKG), to
      dioxygen initiates oxidation in crystallo. Glycol (from epsilonA) and hemiaminal
      (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-meC)
      is also proposed, based on crystallographic observations and computational
      analysis. The observation of these unprecedented intermediates provides direct
      support for the oxidative demethylation mechanism for these demethylases. This
      study also depicts a general mechanistic view of how a methyl group is
      oxidatively removed from different biological substrates.

PMID- 21068849
TI  - Bending loss of elliptical-hole core circular-hole holey fibers bent in arbitrary
      bending directions.
AB  - A holey fiber having a core with an elliptical-hole lattice structure, which is
      referred to as an elliptical-hole core circular-hole holey fiber (EC-CHF), can be
      easily designed as a single-polarization fiber by using the fundamental space
      filling modes of the core and cladding lattices. However, because the guided mode
      in an EC-CHF has a polarization that arises from the large geometric anisotropy
      of the core lattice, the influence of the bending direction on the bending loss
      is a crucial issue for the practical implementation of EC-CHFs. Here, the bending
      losses of an EC-CHF bent in arbitrary angular orientations with respect to the
      core cross section are calculated numerically using the equivalent anisotropic
      step-index circular fiber model for a real EC-CHF, and the influence of the
      bending direction of the fiber on the bending loss is discussed.

PMID- 21068850
TI  - In-band optical signal-to-noise ratio monitoring method based on high-resolution
      polarization analysis and induced differential group delay.
AB  - We report on an in-band optical signal-to-noise ratio monitoring technique for
      wavelength division multiplexed channels. Our proposal relies on the different
      degree of polarization between the signal (highly polarized) and the noise (not
      polarized). Using this principle, we divide the signal under test into two
      orthogonal polarization components and induce a differential group delay via a
      controlled birefringence apparatus that produces a wavelength-dependent shift of
      the polarization state of the signal. After a linear polarizing filter, high
      resolution spectral analysis allows measurement of the amplified spontaneous
      emission noise level. The method is tested by experimental measurements of a 40
      Gbit/s differential phase-shift keying channel showing very good performance.

PMID- 21068851
TI  - Generation of three-dimensional dark spots with a perfect light shell with a
      radially polarized Laguerre-Gaussian beam.
AB  - The theoretical analyses in this paper show that a highly focused double-ring
      radially polarized Laguerre-Gaussian beam with a topological charge of 1 (R
      LG(11)) can generate a small three-dimensional (3D) dark spot surrounded by an
      almost 100% uniform light shell in all directions. The cleanness and size of the
      3D dark spot, the uniformity and strength of the light shell surrounding the dark
      spot, and the light efficiency all depend on the truncation parameter beta of the
      R-LG(11) beam and the numerical aperture (NA) of the system. When beta=1.6 and
      the NA is close to its utmost, an almost 100% uniform light shell surrounding the
      3D dark spot can be achieved and the dark spot is very clean. If the NA is
      lowered but beta is increased to 1.95, we can also achieve an almost 100% uniform
      light shell and light efficiency can reach 90%, but the disadvantage is that the
      center of the dark spot is not too clean. A not-too-clean 3D dark spot, if the
      light shell surrounding it is very uniform, is acceptable for many applications.
      Therefore, 3D dark spots surrounded by a high uniform light shell, generated by
      simply adjusting the truncation parameter of the R-LG(11) beam and the NA of the
      system, are useful for superresolution fluorescence microscopy, dark spot
      microscopy, and the dark spot trap.

PMID- 21068852
TI  - Inhomogeneous phase shifting: an algorithm for nonconstant phase displacements.
AB  - In this work, we have developed a different algorithm than the classical one on
      phase-shifting interferometry. These algorithms typically use constant or
      homogeneous phase displacements and they can be quite accurate and insensitive to
      detuning, taking appropriate weight factors in the formula to recover the wrapped
      phase. However, these algorithms have not been considered with variable or
      inhomogeneous displacements. We have generalized these formulas and obtained some
      expressions for an implementation with variable displacements and ways to get
      partially insensitive algorithms with respect to these arbitrary error shifts.

PMID- 21068853
TI  - Simultaneous strain and temperature measurement using a compact photonic crystal
      fiber inter-modal interferometer and a fiber Bragg grating.
AB  - An all-fiber sensor scheme for simultaneous strain and temperature measurement is
      presented. The sensing head is formed by serially connecting a polarization
      maintaining photonic-crystal-fiber-based inter-modal interferometer (IMI) with a
      fiber Bragg grating (FBG). The IMI, exhibiting an opposite strain response as
      compared to that of the FBG, is highly sensitive to strain, while it is
      insensitive to temperature. This has potential for improving the strain and
      temperature measurement resolutions. A sensor resolution of +/-8.3 MUepsilon in
      strain and +/-2  degrees C in temperature are experimentally achieved within a
      strain range of 0-957.6 MUepsilon and a temperature range of 24  degrees C-64 
      degrees C, respectively.

PMID- 21068854
TI  - High-power widely tunable thulium fiber lasers.
AB  - Applications requiring long-range atmospheric propagation are driving the
      development of high-power thulium fiber lasers. We report on the performance of
      two different laser configurations for high-power tunable thulium fiber lasers:
      one is a single oscillator utilizing a volume Bragg grating for wavelength
      stabilization; the other is a master oscillator power amplifier system with the
      oscillator stabilized and made tunable by a diffraction grating. Each
      configuration provides >150 W of average power, >50% slope efficiency, narrow
      output linewidth, and >100 nm tunability in the wavelength range around 2 MUm.

PMID- 21068855
TI  - Integrated microinterferometric sensor for in-plane displacement measurement.
AB  - We present an integrated sensor based on a grating interferometer (GI) for in
      plane displacement measurement in microregions of large engineering structures.
      The system concept and design, based on a monolithic version of Czarnek's GI, is
      discussed in detail. The technology chain of the GI measurement head (MH),
      including the master fabrication and further replication by means of hot
      embossing, is described. The numerical analyses of the MH by means of geometric
      ray tracing and scalar wave propagation are provided. They allow us to determine
      geometrical tolerance values as well as refractive index homogeneity and
      nonflatness of MH working surfaces, which provide proper beam guiding. Finally
      the demonstrative measurement performed with a model of the sensor is presented.

PMID- 21068856
TI  - Transient response of a resonator fiber optic gyro with triangular wave phase
      modulation.
AB  - We present an in-depth analysis of the transient response of a resonator fiber
      optic gyro based on triangular wave phase modulation. Unusual effects have been
      observed in the process of tracking the resonant frequency of an optical fiber
      ring resonator (OFRR). There is a distortion phenomenon, unlike the ideally
      square wave or a pure DC output of the OFRR, but signal overshoot or undershoot
      occurs. A deep analysis of the influence of the nonideal square wave or pure DC
      output on gyro performance is fully developed for the first time, to the best of
      our knowledge. Further analysis shows that this is the transient response process
      after modulation by the triangular wave, and the process is related both to the
      parameters of the OFRR and the modulation frequency of the triangular wave. By
      sampling the steady-state signal of the distortion square wave, or by
      oversampling the distortion signal to get a number of data, and then accumulating
      and averaging these data to be demodulated, the distortion's effect can be
      considerably decreased.

PMID- 21068857
TI  - Simple iodine reference at 1064 nm for absolute laser frequency determination in
      space applications.
AB  - Using an iodine cell with fixed gas pressure, we built a simple frequency
      reference at 1064 nm with 10 MHz absolute accuracy and used it to demonstrate
      deterministic phase locking between two single-frequency lasers. The reference
      was designed to be as simple as possible, and it does not use a cooler or
      frequency modulator. This system should be useful, especially for space
      interferometric missions such as the Laser Interferometer Space Antenna.

PMID- 21068858
TI  - Two-spherical-wave ultraviolet interferometer for making an antireflective
      subwavelength periodic pattern on a curved surface.
AB  - An ultraviolet two-spherical-wave interferometer was developed in order to make a
      subwavelength structured surface on a curved surface. The change in fringe period
      on the curved surface was significantly suppressed compared with the two-plane
      wave interferometer. The optical setup method for suppressing the change in
      fringe period is described. The effect of the two-spherical-wave interferometer
      was investigated by numerical simulations. In an experimental demonstration for a
      concave spherical surface with 11.1 mm radius of curvature and 10 mm diameter,
      the change in period of the photoresist pattern was reduced to 12 nm for the
      target period of 250 nm.

PMID- 21068859
TI  - Point-spread function of the ocean color bands of the Moderate Resolution Imaging
      Spectroradiometer on Aqua.
AB  - The Moderate Resolution Imaging Spectroradiometer (MODIS) on the Aqua platform
      has nine spectral bands with center wavelengths from 412 to 870 nm that are used
      to produce the standard ocean color data products. Ocean scenes usually contain
      high contrast due to the presence of bright clouds over dark water. About half of
      the MODIS Aqua ocean pixels are flagged as spatial stray light contaminated. The
      MODIS has been characterized for stray light effects prelaunch. In this paper, we
      derive point-spread functions for the MODIS Aqua ocean bands based on prelaunch
      line-spread function measurements. The stray light contamination of ocean scenes
      is evaluated based on artificial test scenes and on-orbit data.

PMID- 21068860
TI  - Satellite image deconvolution based on nonlocal means.
AB  - The deconvolution of blurred and noisy satellite images is an ill-posed inverse
      problem, which can be regularized under the Bayesian framework by introducing an
      appropriate image prior. In this paper, we derive a new image prior based on the
      state-of-the-art nonlocal means (NLM) denoising approach under Markov random
      field theory. Inheriting from the NLM, the prior exploits the intrinsic high
      redundancy of satellite images and is able to encode the image's nonsmooth
      information. Using this prior, we propose an inhomogeneous deconvolution
      technique for satellite images, termed nonlocal means-based deconvolution (NLM
      D). Moreover, in order to make our NLM-D unsupervised, we apply the L-curve
      approach to estimate the optimal regularization parameter. Experimentally, NLM-D
      demonstrates its capacity to preserve the image's nonsmooth structures (such as
      edges and textures) and outperforms the existing total variation-based and
      wavelet-based deconvolution methods in terms of both visual quality and signal-to
      noise ratio performance.

PMID- 21068861
TI  - Plasmon field enhancement in silver core-protruded silicon shell nanocylinder
      illuminated with light at 633 nm.
AB  - We show, to the best of our knowledge, the first simulation result of the strong
      plasmonic field coupling and enhancement at the Ag/Si interface of a silver
      core/protruded silicon shell nanocylinder by using the finite-element method. The
      strong plasmon field, with a slow effective phase velocity accumulated at the
      Ag/Si interface, which results from the large effective index of the surface
      plasmon due to the nearly identical real parts with opposite signs of the
      permittivities of silver and silicon at 633 nm, is analyzed. When the silicon
      shell has shallow protrusions of proper periodicity to meet the phase matching
      condition between the incident light and the surface plasmon wave at the Ag/Si
      interface, a higher scattered electric field and a higher sensitivity to the
      refractive index change of the surrounding medium can be achieved. Furthermore, a
      feasible implementation of the core-shell nanocylinder design concept is studied
      and discussed.

PMID- 21068862
TI  - Robust image watermarking scheme against geometric attacks using a computer
      generated hologram.
AB  - Robustness against geometric attacks is one of the most important issues in
      digital watermarking. A novel geometric robust watermarking scheme that uses
      computer-generated holograms as the watermark is presented. To maintain
      imperceptibility and robustness, a quantization embedding algorithm is adopted to
      embed the mark hologram into the low-frequency subband of the wavelet-transformed
      host image. In the detection process, the geometric distorted watermarked images
      are recovered first by the proposed improved geometric correction method, which
      is based on the scale invariant feature transform, the invariant centroid, and
      the pulse coupled neural network. Then the mark holograms are extracted from the
      recovered images. In comparison with the traditional geometric estimation method,
      the suggested improved geometric correction method can estimate the geometric
      distortion parameters more accurately and needs less auxiliary information.
      Compared with other watermark schemes using digital holograms, the proposed
      method has the distinct advantage of robustness to geometric attacks. The
      experimental results demonstrate that the proposed method has good robustness to
      resist geometric attacks and common attacks including rotation, scaling,
      translation, image flipping, combined attacks, filtering, occlusion, cropping,
      and JPEG compression.

PMID- 21068863
TI  - Modeling dielectric half-wave plates for cosmic microwave background polarimetry
      using a Mueller matrix formalism.
AB  - We derive an analytic formula using the Mueller matrix formalism that
      parameterizes the nonidealities of a half-wave plate (HWP) made from dielectric
      antireflection-coated birefringent slabs. This model accounts for frequency
      dependent effects at normal incidence, including effects driven by the
      reflections at dielectric boundaries. The model also may be used to guide the
      characterization of an instrument that uses a HWP. We discuss the coupling of a
      HWP to different source spectra, and the potential impact of that effect on
      foreground removal for the SPIDER cosmic microwave background experiment. We also
      describe a way to use this model in a mapmaking algorithm that fully corrects for
      HWP nonidealities.

PMID- 21068864
TI  - Measurement of the optical properties of a two-layer model of the human head
      using broadband near-infrared spectroscopy.
AB  - We present the development of a continuous-wave method of quantifying the optical
      properties of a two-layered model of the human head using a broadband spectral
      approach. Absolute absorption and scattering properties of the upper and lower
      layers of phantoms with known optical properties were reconstructed from steady
      state multi-distance measurements by performing differential fit analysis of the
      near-infrared reflectance spectrum between 700 and 1000 nm. From spectra acquired
      at 10, 20, and 30 mm, the concentration of a chromophore in the bottom layer was
      determined within an error of 10% in the presence of a 15 mm thick top layer.
      These results demonstrate that our method was able to determine the optical
      properties of the lower layer, which represents brain, with acceptable error at
      specific source-detector distances.

PMID- 21068865
TI  - Expansion of the dynamic range of statistical interferometry and its application
      to extremely short- to long-term plant growth monitoring.
AB  - In this study, we propose a method to expand the dynamic range of expansion or
      strain measurement using statistical interferometry. Statistical interferometry
      is a very accurate interferometric technique that is applicable to practical
      rough surface objects [Opt. Lett. 16, 883 (1991); J. Opt. Soc. Am. A 18, 1267
      (2001)]. It is based on the statistical stability of a fully developed speckle
      field and was successfully applied to measure the growth of plants in our
      previous study [Environ. Exp. Bot. 64, 314 (2008); J. For. Res. 12, 393 (2007)].
      However, the measurable range of the expansion of the object was restricted to
      less than one wavelength of the light used. Improvement of the dynamic range is
      confirmed experimentally in this work by introducing a large expansion up to 300
      MUm while keeping the precision of measurement high. Next, the improved system is
      applied to monitor plant growth from the subnanometric scale to several hundreds
      of micrometers under some environmental conditions. These features of the method
      make it especially worthwhile in botanical and agricultural studies.

PMID- 21068866
TI  - Comparative study of mid-infrared fibers for modal filtering.
AB  - We compare the filtering capabilities of two infrared fibers developed to achieve
      a high rejection ratio of the higher order modes in order to obtain compact modal
      filters devoted to stellar interferometry. Two types of double-clad fibers are
      studied: a fiber with a second thin absorbing cladding and a fiber with a second
      thick absorbing cladding closer to the fiber core; both are single mode around
      the CO(2) band (10.6 MUm). We present the single-mode spectral domain and the
      nulling capabilities of both fibers for different fiber lengths, comparing
      simulations with experimental results. We show that the filtering capabilities
      are improved when the absorbing clad is closer to the fiber core, as the
      propagation distance needed to filter out these modes is shorter. Thus, to obtain
      high rejection ratios in compact devices, an absorbing cladding close to the core
      of the fiber is compulsory in order to suppress cladding modes that could
      eventually recouple into the waveguide. We present an empirical model that allows
      determining the minimum filter length, considering only one effective leaky mode
      with low attenuation, which considerably simplifies the theoretical studies.

PMID- 21068867
TI  - Two-photon fluorescence excitation spectroscopy by pulse shaping ultrabroad
      bandwidth femtosecond laser pulses.
AB  - A fast and automated approach to measuring two-photon fluorescence excitation
      (TPE) spectra of fluorophores with high resolution (~2 nm) by pulse shaping
      ultrabroad-bandwidth femtosecond laser pulses is demonstrated. Selective
      excitation in the range of 675-990 nm was achieved by imposing a series of
      specially designed phase and amplitude masks on the excitation pulses using a
      pulse shaper. The method eliminates the need for laser tuning and is, thus,
      suitable for non-laser-expert use. The TPE spectrum of Fluorescein was compared
      with independent measurements and the spectra of the pH-sensitive dye 8
      hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in acidic and basic environments were
      measured for the first time using this approach.

PMID- 21068868
TI  - Durham adaptive optics real-time controller.
AB  - The Durham adaptive optics (AO) real-time controller was initially a proof of
      concept design for a generic AO control system. It has since been developed into
      a modern and powerful central-processing-unit-based real-time control system,
      capable of using hardware acceleration (including field programmable gate arrays
      and graphical processing units), based primarily around commercial off-the-shelf
      hardware. It is powerful enough to be used as the real-time controller for all
      currently planned 8 m class telescope AO systems. Here we give details of this
      controller and the concepts behind it, and report on performance, including
      latency and jitter, which is less than 10 MUs for small AO systems.

PMID- 21068869
TI  - Statistical properties of finite-bandwidth radiation scattered by random
      amplitude screens and random phase screens.
AB  - We investigate the effect of finite bandwidth of the incident radiation on
      scattering by thin layers that introduce random phase or amplitude variations. In
      particular, we calculate the scintillation index of the propagating radiation for
      smoothly varying and fractal phase screens and for random telegraph wave and
      checkerboard amplitude screens. Increasing the bandwidth of the incident
      radiation reduces the fluctuations of the scattered intensity over the whole
      propagation path, except in the case of the smoothly varying phase screen, where
      geometrical optics features in the pattern persist in the focusing region.

PMID- 21068870
TI  - Patents.
AB  - 5,379,149; 5,392,079; 5,404,247; 5,412,469; 5,414,439; 5,414,561; 5,416,325;
      5,418,380; 5,420,947; 5,422,723.

PMID- 21068871
TI  - Grating triplet.
AB  - A grating-pair device is useful for producing negative group velocity dispersion
      of temporal optical signals. When high dispersion is needed or large bandwidth is
      involved, higher-order dispersion terms become significant. The grating triplet
      is a new approach to create dispersion that can produce negative or positive
      group-velocity dispersion without higher-order dispersion terms.

PMID- 21068872
TI  - Visualization of surface figure by the use of Zernike polynomials.
AB  - Commercial software in modern interferometers used in optical testing frequently
      fit the wave-front or surface-figure error to Zernike polynomials; typically 37
      coefficients are provided. We provide visual representations of these data in a
      form that may help optical fabricators decide how to improve their process or how
      to optimize system assembly.

PMID- 21068873
TI  - Fraunhofer diffraction of a slit aperture between a knife-edge and a metal
      cylinder.
AB  - The Fraunhofer diffraction pattern of a slit aperture formed between a reference
      knife-edge and a metal-cylinder surface is different from that of an ideal slit
      aperture. This pattern should include reflected light coming from both the front
      and rear sides of a cylinder surface. To investigate the influence of light
      reflected from the cylinder surface, we discuss the theoretical consideration
      based on the simple model of the reflected light on the surface. The experimental
      setup is designed and constructed to measure the actual diffraction pattern
      produced by the slit between the knife-edge and the cylinder surface. As a result
      it is obvious that the reflection of diffracted light on the rear side is
      dominant in both the simulation and the experiment.

PMID- 21068874
TI  - Colorless gradient-index cylindrical lenses with high numerical apertures
      produced by silver-ion exchange.
AB  - Colorless gradient-index cylindrical lenses with high numerical apertures in
      slabs 200-1000 um thick have been fabricated by silver-sodium ion exchange in a
      specially developed glass. The lenses with numerical apertures of 0.6 are
      characterized by index profiles and by spherical and chromatic aberration. On
      axis focusing properties and the application to the collimation of high-power
      laser diode bars are discussed.

PMID- 21068875
TI  - Eight-frame holographic interferometry system for transient plasma diagnostics.
AB  - A multiframe technique that uses Fresnel holography is described. Splitting of
      the initial pulse by means of 50/50 beam splitters provides two sets of eight
      consecutive pulses with approximately the same energy but with different angles.
      Each interferogram is recorded separately. The technique has been used to obtain
      time-resolved Fresnel holographic interferograms of transient electrical
      discharges, such as Z pinch. A frequency-doubled, Q-switched Nd:YAG laser (6-ns
      FWHM) is used. A delay between consecutive pulses of 10 ns is achieved, and it is
      mainly limited by the physical size of the laboratory. Interferograms obtained on
      a gas-embedded Z pinch are shown.

PMID- 21068876
TI  - Absorbing beam splitter in a Michelson interferometer.
AB  - The equality of the reflected and the transmitted irradiances by a beam splitter
      that consists of a thin absorbing coating (typically a metallic film) on a
      transparent plate is considered. The absorption and the phase difference between
      the reflected and transmitted fields are also studied. The lack of reversibility
      of this beam splitter introduces an asymmetry that is discussed for a Michelson
      interferometer.

PMID- 21068877
TI  - Solgel alumina coating for hollow waveguide delivery of CO(2) laser radiation.
AB  - Solgel alumina films were prepared by use of the Yoldas process and were
      characterized optically and microstructurally. From nitrogen adsorption and
      electron microscopy, we determined that the material was highly porous, with
      pores and crystallites of the order of tens of nanometers in size. The infrared
      transmission and reflectance of the films were measured, and dispersion curves
      were calculated as a function of firing temperature by extracting the film
      optical constants from the reflectance and thickness data. The use of this
      material in a hollow waveguide structure for the delivery of CO(2) laser
      radiation for surgical applications is discussed. Calculated waveguide losses
      indicate that solgel-based alumina is a good candidate material for this
      application.

PMID- 21068878
TI  - A high-gain, compact, nonimaging concentrator: RXI.
AB  - The design procedure of a new nonimaging concentrator (called an RXI) is
      explained. Rays that impinge on the concentrator aperture, within the acceptance
      angle, are directed to the receiver by means of one refraction, one reflection,
      and one total internal reflection. The concentrator can be made as a single
      dielectric piece (in which the receiver is immersed) whose aspect ratio
      (thickness/aperture diameter) is close to 1/3. Ray-tracing analysis of a
      rotational symmetric RXI shows total transmissions of greater than 94.5% (no
      absorption or reflection losses are considered) when the acceptance angle of the
      incoming rays is small (<3 degrees ) and when the receiver area is the smallest
      possible (maximal concentration.).

PMID- 21068879
TI  - Multipass V-shaped system with a large relative aperture: stages of development.
AB  - In this review I describe the step-by-step development and update of an optical
      multipass system with a fixed path length and large relative aperture. The system
      has been researched off and on for 20 years. Contrary to acknowledged ideas, some
      of the models were designed using the ratio between the base length of a
      multipass system and the focal length of an objective equal to 1.5 (compared with
      2 for the classical White system). Such an unconventional choice of 1.5f base
      length between opposite mirrors ensured the development of a cycle of six-pass
      single-objective systems with a large relative aperture. The described systems
      were used in various gas analytical equipment. Of special interest is an original
      scheme with an f-number of 3.7 to be used in high-resolution spectroscopy.

PMID- 21068880
TI  - Contours of the constant third Brewster angle in the complex plane of a
      dielectric constant.
AB  - Three special angles associated with the external reflection of light at the
      surface of an absorbing medium are well known: the principal angle, the pseudo
      Brewster angle, and the second Brewster angle. Another significant angle has been
      identified recently by Azzam and El-Saba [Appl. Opt. 28, 1365 (1989)]. At this
      angle, the slope of the differential reflection phase shift with respect to the
      angle of incidence is maximum negative. For convenience it is called the third
      Brewster angle. The nature of the contours of the constant third Brewster angle
      in a complex dielectric constant plane is considered both analytically and
      graphically in comparison with the other constant special-angle contours.

PMID- 21068881
TI  - Simplified approach to the Jones calculus in retracing optical circuits.
AB  - The application of the Jones calculus to optical circuits in which
      counterpropagating light beams are present is discussed, with particular
      attention to the conventions associated with the Jones calculus for the
      description of the polarization state of an optical beam and to the reference
      system adopted. The reference system adopted here differs from that used by
      Jones, but it exploits a simpler formalism when used to describe complex optical
      systems where multiple reflections take place. The differences between these two
      reference systems are pointed out with particular attention to the behavior of
      nonreciprocal optical devices and reflectors. An application of the results to a
      simple optical circuit is presented.

PMID- 21068882
TI  - Tailoring lighting reflectors to prescribed illuminance distributions: compact
      partial-involute designs.
AB  - Reflectors for lighting can be tailored to produce the desired flux maps
      (illuminance distributions) precisely, from extended light sources, with a
      calculational procedure called tailored edge-ray designs (TED's). We generalize
      the TED procedure, which has so far been developed only for flat sources, to
      tubular sources within partial-involute reflectors. The governing differential
      equations for the reflectors are solved analytically. We present specific results
      for the practical problem of producing uniform far-field illuminance in symmetric
      two-dimensional luminaires. It is demonstrated that, relative to flat-source
      TED's, these new designs can offer increased uniform core regions, more compact
      reflectors, and better glare control. We offer a comprehensive analysis of the
      flux map and geometric properties of partial-involute TED's. Further improvements
      are possible with hybrid combinations, as we illustrate with several design
      examples.

PMID- 21068883
TI  - Compact imaging spectrograph for broadband spectral simultaneity.
AB  - We report on the design of a small spectrograph that is capable of imaging
      several thousand angstrom simultaneously at a moderate spectral resolution. The
      prototype instrument included a number of developmental items that were used to
      assess their utility in this and other applications. Some we would recommend
      using again, some we would not. In the configuration that was built and tested,
      the instantaneous wavelength range was chosen to be 3700-11,700 A. However, the
      wavelength range could be selected for a lower wavelength, as low as ~ 1200 A.
      The spectral imaging was achieved with an intensified-CCD focal-plane detector.
      The broad wavelength coverage was achieved with a matrix of four diffraction
      gratings and a custom-designed photocathode system. The photocathode was
      specially built to provide a response over the chosen broad wavelength range by
      use of a single image intensifier. The theoretical spectral resolution of the
      instrument varied from 12 to 20 A depending on waveleng th segment. A higher
      spectral resolution can be selected at the expense of total wavelength coverage.
      The optical system was designed to be moderately fast (f/6) when considered at
      the level of each of the four optical subchannels and suitable for use on
      relatively weak airglow signals. The instrument was designed to be readily
      portable, weighing 15 kg, with an envelope of 37 cm * 37 cm * 48 cm. The
      advantages and weaknesses of such an instrument are discussed, and improvements
      are suggested for specific applications. This study represents a stepping stone
      in the evolution of electronic spectrographs and leads to later designs that are
      currently being evaluated.

PMID- 21068884
TI  - Development of a multichannel Fourier transform spectrometer.
AB  - We devised a novel type of multichannel Fourier transform spectrometer (MCFTS)
      that incorporates a Wollaston prism, polarizing interferometer combined with two
      Savart plates and a phase-retarding plate. This original MCFTS produces a number
      of lines of folded interferograms recorded with a two-dimensional imaging
      detector such as a CCD detector. In the present type of MCFTS, the total incident
      light is available except for a small amount of reflection loss. It is possible
      to enhance the signal-to-noise ratio. The enhancement of the resolving power is
      also expected by the connection of the interferograms with a newly developed
      method.

PMID- 21068885
TI  - Determining the refractive index and average thickness of AsSe semiconducting
      glass films from wavelength measurements only.
AB  - The dispersive refractive index n(lambda) and thickness d of chalcogenide glass
      thin films are usually calculated from measurements of both optical transmission
      and wavelength values. Many factors can influence the transmission values,
      leading to large errors in the values obtained for n(lambda) and d. Anovel
      optical method is used to derive n(lambda) and d for AsSe semiconducting glass
      thin films deposited by thermal evaporation in the spectral region where k(2) "
      n(2), using only wavelength values. This entails obtaining two transmission
      spectra: one at normal incidence and another at oblique incidence. The procedure
      yields values for the refractive index and average thickness of thermally
      evaporated chalcogenide films to an accuracy better than 3%.

PMID- 21068886
TI  - Quartz-halogen D65 simulation.
AB  - A new CIE daylight D65 filter has been developed for a quartz-halogen source
      operating at a color temperature in the region of 3000 K. The filter is a serial
      type comprising optical filter glasses and multilayer thin-film stacks. Extremely
      close agreement is obtained between the spectral-power distribution associated
      with the filter-source combination and that of daylight D65.

PMID- 21068887
TI  - Design of grazing-incidence multilayer supermirrors for hard-x-ray reflectors.
AB  - Extremely broadband grazing-incidence multilayers for hard-x-ray reflection can
      be obtained by a gradual change of the layer thicknesses down through the
      structure. Existing approaches for designing similar neutron optics, called
      supermirrors, are shown to provide respectable performance when applied to x-ray
      multilayers. However, none of these approaches consider the effects of imperfect
      layer interfaces and absorption in the overlying layers. Adaptations of neutron
      designs that take these effects into account are presented, and a thorough
      analysis of two specific applications (a single hard-x-ray reflector and a hard-x
      ray telescope) shows that an improved performance can be obtained. A multilayer
      whose bilayer thicknesses are given by a power law expression is found to provide
      the best solution; however, it is only slightly better than some of the adapted
      neutron designs.

PMID- 21068888
TI  - Transmittance of a thin Saran film in the 45-584-A wavelength region.
AB  - The transmittance of a free-standing Saran film, 4260 A thick, has been measured
      by means of synchrotron radiation in the 45-584-A wavelength region. The
      transmittance was calculated by means of the elemental composition of the film
      material as determined by x-ray photoelectron spectroscopy and the optical
      constants as derived from atomic-scattering factors. The calculated transmittance
      agreed with the measured transmittance in the 45-150-A wavelength region. The
      calculated transmittance was significantly lower than that measured for the
      wavelength range 150-340 A. This difference implies that molecular effects that
      are not accounted for by atomic-scattering factors become increasingly important
      at the longer wavelengths.

PMID- 21068889
TI  - Contours of constant minimum-reflectance and maximum-reflectance angles in the
      complex plane of a dielectric constant for incident light of arbitrary
      polarization.
AB  - The reflectance of an absorbing medium for incident light of arbitrary
      polarization can exhibit two extrema at angles of incidence phi(max) and
      phi(min). The behavior of iso-phi(max) and iso-phi(min) contours in the complex
      plane of a dielectric constant for various incident polarizations is analyzed.

PMID- 21068890
TI  - Characterization of an optical-fiber reflectometer for in situ measurement
      applications.
AB  - We present studies of apparatus based on optical-fiber probes for measuring the
      reflectivity of opaque materials. The probes are designed for in situ
      applications at high temperatures and in situations for which access is
      difficult. First, we present a method in which the hemispherical reflectivity and
      the angular distribution of the reflected flux are obtained from bidirectional
      measurements. Second, we describe a method to measure the reflectivity in only
      the normal direction; this method is available only for diffuse materials. Both
      methods of use of the device were validated through the use of commercial diffuse
      standards and specific materials with particular surface microstructures.

PMID- 21068891
TI  - Improved integrating-sphere throughput with a lens and nonimaging concentrator.
AB  - A reflectometer design utilizing an integrating sphere with a lens and nonimaging
      concentrator is described. Compared with previous designs where a collimator was
      used to restrict the detector field of view, the concentrator-lens combination
      significantly increases the throughput of the reflectometer. A procedure for
      designing lens-concentrators is given along with the results of parametric
      studies. The measured angular response of a lens-concentrator system is compared
      with ray-trace predictions and with the response of an ideal system.

PMID- 21068892
TI  - Correction of static optical errors in a segmented adaptive optical system.
AB  - Adaptive optical systems are designed to compensate for wave-front errors caused
      by atmospheric turbulence. In addition, they may also correct for wave-front
      errors associated with fixed optical aberrations in the host telescope. In
      general, however, adaptive optical systems cannot sense wave-front errors caused
      by imperfections in their own internal optical components. Consequently, these
      fixed internal errors will remain uncorrected. The problem of fixed internal
      aberrations has been noted in a segmented adaptive optics system designed for
      solar astronomy. This problem has been eliminated by measurement of the fixed
      errors, off line, through the use of a simple adaptation of a Hartmann test.
      Results from a recent experiment demonstrating the correction of the errors are
      presented.

PMID- 21068893
TI  - Deformation of the modulation profile in phase holographic gratings.
AB  - Among all the parameters that characterize a phase grating, the most difficult to
      control is the modulation profile of the refractive index. In fact, it covers
      many scalar parameters that are the Fourier coefficients of the profile. To study
      the influence of processing baths on the modulation profile, in phase holographic
      gratings made of dichromated gelatin, we have observed that the shape of the
      profiles obtained sometimes presents a slight concavity or a convexity in the
      middle, leading to an increase or a decrease in the diffraction efficiency. We
      present the experimental results and a numerical study in the form of a
      theoretical prediction, which confirms the experimental observations.

PMID- 21068894
TI  - Transverse mode analysis of a laser beam by near- and far-field intensity
      measurements.
AB  - A quantitative measurement of laser-beam quality can be performed by
      determination of the presence of multiple transverse modes of the laser
      oscillator and by calculation of their power content. Along this line of
      argument, we discuss a new approach that, starting from near-field and far-field
      intensity measurements, can evaluate the complex excitation coefficients of the
      transverse modes in a laser beam. The exploitation of near-field measurements
      sharply improves the performances of the technique in those cases in which only
      far-field measurements are used. The validity of the method is confirmed by
      several accurate numerical simulations and by some experimental results relative
      to a multimode Q-switched Nd:YAG laser.

PMID- 21068895
TI  - Nonlinear optical behavior of ocular tissue during laser irradiation.
AB  - A pump (cw Ho-YAG laser) and probe (He-Ne laser) system was used to study the
      dynamics of the optical behavior of ocular tissue during laser heating. The
      nonlinear optical behavior of porcine corneal and vitreous-humor tissue was
      characterized in vitro by means of measurements of the radial profile of a He-Ne
      laser beam transmitted through the tissue. Temperature gradients in the tissue
      created by the absorption of pump radiation caused the probe beam to diverge. For
      constant laser power, the rate of divergence was made dependent on the spot size
      of the pump beam. The profile of the transmitted probe beam returned to its
      original magnitude and shape after the tissue was permitted to cool. This
      reversible change in optical behavior was attributed to the formation of a
      negative lens owing to thermally induced local gradients in the refractive index
      of the tissue.

PMID- 21068896
TI  - Pupil exploration and wave-front-polynomial fitting of optical systems.
AB  - Pupil exploration and wave-front-polynomial fitting algorithms are tools that are
      often employed in image-quality evaluation techniques, such as optical-transfer
      function and point-spread-function calculations. These techniques require that
      aberration data be determined for a large number of points across the pupil. With
      optical systems increasing in complexity, it is necessary that these algorithms
      become more sophisticated to ensure that the proper pupil shapes and aberration
      maps are used to represent the wave fronts. Such algorithms are described. These
      algorithms can handle systems that not only lack the symmetry found with the more
      conventional lens systems but those that also have apertures with unusual shapes.
      As practical demonstrations the treatments employed in the pupil exploration and
      the wave-front-polynomial fitting have been applied to various lens arrangements
      and the results discussed.

PMID- 21068897
TI  - Calculation of speckle displacement, decorrelation, and object-point location in
      imaging systems.
AB  - My purpose here is to outline a method for calculating the fundamental behavior
      of speckle patterns in imaging systems. The theory of speckle displacement and
      decorrelation to include imaging at a general oblique angle is extended to more
      imaging systems, and explicit formulas are given for the image-point-object-point
      relationship that is important when defocused speckle is used. The intermediate
      results can be reused for optical systems other than those presented here. The
      image-speckle displacement analyzed in the three systems is expressed
      equivalently. The speckle decorrelation is in general larger in a single-lens
      system than in a two-lens system and can be minimized by proper design of the
      system.

PMID- 21068898
TI  - Integrated optical waveguides: refractive-index profile control by temperature
      and electric-field programming.
AB  - Ion exchange is often used to manufacture integrated optical waveguides in
      glasses and crystals. The manufacture of low-loss, compact, integrated optical
      waveguides can be achieved by varying the processing conditions (the temperature
      and the electric field) during the ion exchange. We have simulated the formation
      of waveguides in glass with a molten salt silver ion-exchange technique and have
      shown that, by simply linearly varying the temperature and electric field during
      processing of waveguides, one can tailor the refractive-index profiles to produce
      low-loss parabolic and hyperbolic secant dopant profiles or any other generic
      dopant profile.

PMID- 21068899
TI  - Optical fiber accelerometer based on a silicon micromachined cantilever.
AB  - An intensity-modulated fiber-optic accelerometer based on backreflection effects
      has been manufactured and tested. It uses a multimode fiber placed at a spherical
      mirror center, and the beam intensity is modulated by a micromachined silicon
      cantilever. This device has applications as an accelerometer and vibrometer for
      rotating machines. It exhibits an amplitude linearity of +/-1.2% in the range of
      0.1-22 m s(-2), a frequency linearity of +/-1% in the range of 0-100 Hz, and a
      temperature sensitivity of less than 0.03%/ degrees C. The sensor is devoted to a
      wavelength-division multiplexing network.

PMID- 21068900
TI  - Erbium-doped silica fibers for intrinsic fiber-optic temperature sensors.
AB  - The variation in the green intensity ratio ((2)H(11/2) and (4)S(3/2) energy
      levels to the ground state) of Er ions in silica fibers has been studied as a
      function of temperature. The different processes that are used to determine the
      population of these levels are investigated, in particular 800-nm excited-state
      absorption in Er-doped fibers and 980-nm energy transfer, in Yb-Er-codoped
      fibers. The invariance of the intensity ratio at a fixed temperature with respect
      to power, wavelength, and doped fiber length has been investigated and shown to
      permit the realization of a high-dynamic-range (greater than 600  degrees C),
      autocalibrated fiber-optic temperature sensor.

PMID- 21068901
TI  - Photon-measurement density functions. Part 2: Finite-element-method calculations.
AB  - This paper presents a method to calculate photon-measurement density functions
      (PMDF's), which were introduced in Part 1 [Appl. Opt. 34, 7395-7409 (1995), for
      near-infrared imaging and spectroscopy in complex and inhomogeneous objects
      through the use of a finite-element model. PMDF's map the sensitivity of a
      measurement on the surface of an object to the perturbations of the optical
      parameters within the object. Data are presented for homogeneous and layered
      circular objects and for a complex two-dimensional model of a head. In particular
      the influence of the optical parameters on the shape of the PMDF and the
      distortions caused by boundary layers and complex inhomogeneties are
      investigated.

PMID- 21068902
TI  - Time-resolved optical imaging of a solid tissue-equivalent phantom.
AB  - A solid plastic phantom has been developed with optical properties that closely
      match those of human breast tissue at near-IR wavelengths. The phantom is a 54-mm
      thick slab containing four small cylinders of contrasting scatter and absorption.
      A detailed description of the phantom is followed by an account of an attempt to
      image the phantom by a time-resolved imaging technique. Images generated with
      transmitted light with the shortest flight times revealed the embedded cylinders
      with greater visibility than images obtained with continuous light
      transillumination. However, images corresponding to flight times of less than
      ~700 ps were severely degraded from a lack of detected photons. An attempt was
      made to overcome this degradation by extrapolating the measured temporal
      distributions with an analytic model of photon transport. Results suggest that
      subcentimeter resolution imaging of low-contrast tumors in the breast is
      scientifically possible. Our phantom is available to any other research groups
      wishing to evaluate their systems.

PMID- 21068903
TI  - Blending polysiloxane glass resins to produce optical films with a specific
      refractive index.
AB  - Commercially available polysiloxane resins can be blended either in the solid
      state or in solution to produce optically transparent films whose refractive
      index is a linear function of the weight percent of one component. Useful
      applications for these "glass resins" include protective coatings for hydroscopic
      optical crystals, antireflective or index-matching films, and homeotropic
      alignment layers for liquid crystal devices.

PMID- 21068904
TI  - Modulation Transfer Function Measurement Using Three- and Four-bar Targets.
AB  - Modulation-transfer-function (MTF) measurement often involves the use of three-
      and four-bar resolution targets. In the conversion of three- and four-bar image
      data to MTF, biased results can occur when we use series-expansion techniques
      appropriate for square-wave targets of infinite extent. For systems where the
      image data are digitally recorded, a convenient and accurate conversion of bar
      target data to MTF can be performed using a Fourier-domain method.

PMID- 21068905
TI  - Lens curvature measurements by shadow projection profilometry.
AB  - A technique is described for measuring spherical and aspherical lens curvature
      independent of surface contact or dependence on surface smoothness. The shadow of
      a lens profile is projected onto a CCD pixel array, and its silhouette edge
      traced by computer video-image analysis. Nonlinear regression analysis, with
      correction for axial tilt, calculates lens curvature.

PMID- 21068906
TI  - Measurement of focal length using an optical power meter.
AB  - This Note shows that the focal length of a lens maybe calculated from the results
      of three radiometric measurements. The derived expression for focal length is
      valid for both positive and negative lenses.

PMID- 21068907
TI  - Internal loss measurement technique for optical devices equipped with fiber
      connectors at both ends.
AB  - This paper describes a convenient technique for measuring the loss of optical
      devices that have connectors at both ends. The technique can provide both
      bidirectional internal and values temporal connector loss by the mathematical
      solution of four normalized power measurements. Accuracy of the internal loss
      measurement is limited by the need to use four variables that may fluctuate due
      to unsuitable fiber manipulations or leaky modes.

PMID- 21068908
TI  - Zernike-gauss polynomials and optical aberrations of systems with gaussian
      pupils.
AB  - In the first two Notes of this series,(l,2) we discussed Zernike circle and
      annular polynomials that represent optimally balanced classical aberrations of
      systems with uniform circular or annular pupils, respectively. Here we discuss
      Zernike-Gauss polynomials which are the corresponding polynomials for systems
      with Gaussian circular or annular pupils.(3-5) Such pupils, called apodized
      pupils, are used in optical imaging to reduce the secondary rings of the
      pointspread functions of uniform pupils.(6) Propagation of Gaussian laser beams
      also involves such pupils.

PMID- 21068909
TI  - Zernike polynomials and optical aberrations.
AB  - The use of Zernike polynomials to calculate the standard deviation of a primary
      aberration across a circular, annular, or a Gaussian pupil is described. The
      standard deviation of secondary aberrations is also discussed briefly.

PMID- 21068910
TI  - Measuring the surface defects of a fabry-perot etalon.
AB  - A simple method for mapping the surface defects of a Fabry-Perot etalon is
      described. Images of the fringes of equal thickness are acquired as the plate
      separation is altered in a stepwise manner. This information is processed to
      yield a map of the location of the surface defects, and can be further used to
      estimate the effect of varying plate reflectance on the instrument function.

PMID- 21068911
TI  - Dynamic Photoelasticity Using LED and Polaroid Film.
AB  - Dynamic photoelasticity relies on high-speed photographic systems to record the
      fringes in motion. Several systems are being used, but the delayed microflash is
      widely popular in non-destructive studies due to the high-contrast recording and
      low cost. Flash lamps and lasers are routinely employed as the light source in
      these setups. The use of LED as a microflash in such systems is presented.
      Capability of the system is demonstrated by recording fringe patterns from a
      photoelastic model under dynamic loading. A high-speed Polaroid film is used for
      recording the dynamic fringe patterns. Low cost, low power, and simplicity in the
      experimental setup make it possible to adapt the system to undergraduate
      laboratories.

PMID- 21068912
TI  - Plate beamsplitter to produce multiple equal-intensity beams.
AB  - The design of a plate beamsplitter to produce multiple beams of equal intensity
      is presented. Multiple beams of equal intensity can be obtained from a plate by
      varying the reflectances of the front and back surfaces. The application for
      which we designed the plate beamsplitter was a fourbeam multiplexed galvanometric
      scanner for a confocal scanning microscope. Multiplexing with four beams
      increases the effective optical scanning rate (and therefore the confocal imaging
      rate) to four times the electromechanical scanning rate of the galvanometrically
      driven mirrors.

PMID- 21068913
TI  - Novel interferometer based on a wedge prism.
AB  - An uncoated optical wedge and two mirrors form the basis of a very simple unequal
      path interferometer for laboratory use. The optical design is free of ghost
      reflections, works with any source polarization, and does not require optical
      isolation. The interferometer is inexpensive to make and easy to align, and may
      be used for coherence testing, wavelength stabilization, and optical testing.

PMID- 21068914
TI  - Simple optical pulse lengthening setup for the subnanosecond range.
AB  - An easily realizable, passive pulse lengthening method is suggested to increase
      the pulse duration of light pulses originally of 100 psec-1 nsec length. The
      method applies an unidirectional light loop based on total internal reflections
      and polarization selectivity of the glass/air interface.

PMID- 21068915
TI  - Lens Design for the Near IR ... Correction of Primary Chromatic Aberration.
AB  - The dispersion characteristic of conventional optical glass types will vary as a
      function of the wavelength region being considered. In the 1.0 to 1.5 um region,
      the dispersion of traditional crown and flint glass types is found to be nearly
      the same. This results in a unique condition when attempting a lens design
      solution for this spectral region. A typical example is described here that will
      be helpful in understanding this phenomenon.

PMID- 21068916
TI  - Uniaxial stress apparatus for measurements of optical activity.
AB  - A device is described with which the optical activity of crystalline materials
      under stress can be measured. The sample is not moved, but a three-axis rotation
      is possible.

PMID- 21068917
TI  - Modeling soft contact lenses in raytrace code.
AB  - The surface interferogram feature of raytrace codes is used to model the optical
      performance of soft contact lenses, especially in situations where the lens is
      decentered. The contact lens is totally defined by a thickness data file, which
      can easily be shifted relative to the corneal vertex of a schematic eye model.

PMID- 21068918
TI  - Miniature Kinematic Mirror Mount for UHV Service.
AB  - A miniature kinematic mount allows adjustment of mirror pointing inside ultrahigh
      vacuum (UHV) by rotating finely threaded screws outside of vacuum. The mount
      assembly is less than 0.620 in. in diameter, so it fits through the standard
      tubing used with miniature conflat flanges. The mount is a point-iine-plane
      device with a sapphire ball at the point position, so that no lubrication is
      required in vacuum.

PMID- 21068919
TI  - Compensation of chromatic errors in high na molded objective lenses.
AB  - High NA molded glass objective lenses are commercially available for use in the
      680 nm to 850 nm range. We show that a simple positive lens can be used with an
      objective lens to compensate for wavelength-induced aberration in the 400 nm to
      700 nm range. There is a direct relationship between the optimum power of the
      corrector lens and the wavelength of interest. We also show that a single
      positive lens and a holographic optical element can be used with an objective
      lens to compensate for wavelength-induced aberration over a wide range of
      wavelengths.

PMID- 21068920
TI  - A birefringent prism coupler in guided wave experiments.
AB  - A rutile prism was used to excite guided waves in a CdS film. The wave vector
      matching condition was studied under the influence of prism's birefringence.
      Refractive indices and thickness of the film were determined.

PMID- 21068921
TI  - On the use of microbend fiber optic mode strippers and scramblers: cautionary
      note.
AB  - Microbend mode strippers/scramblers are commonly assumed to remove higher order
      modes uniformly. In fact, they only remove higher order modes propagating in the
      plane of the microbends, resulting in an elliptical output pattern from a
      circular fiber.

PMID- 21068922
TI  - Digital recording and numerical reconstruction of holograms: a new method for
      displaying light in flight.
AB  - We present a new method for displaying light in flight. Fresnel holograms are
      recorded directly on a CCD sensor, electronically stored, and numerically
      reconstructed. Experimental results are shown. From different parts of a single
      holographic recording, different views of a wave front can be reconstructed. This
      means that the temporal evolution of a wave front can be observed by numerical
      methods.

PMID- 21068923
TI  - Digital error-signal extraction technique for real-time automatic control of
      optical interferometers.
AB  - We describe an efficient and robust method for the extraction of the longitudinal
      error signal for the automatic control of optical interferometers, which can also
      be applied when the uncontrolled optical system spans hundreds of fringes. The
      method is based on classic modulation techniques (phase modulation, mechanical
      modulation, etc.), but extends their performances by the use of the information
      available only at the output photodiode. We digitally implemented such a method
      by following modular hardware and software architectures. We then tested the
      whole procedure in the automatic control of a suspended Michelson interferometer,
      showing its feasibility and the good performances.

PMID- 21068924
TI  - Transmission bandpass guided-mode resonance filters.
AB  - It is shown that the guided-mode resonance effects associated with waveguide
      gratings can be used to realize transmission bandpass filters. The key idea is
      the integration of the resonant waveguide gratings into a dielectric multilayer
      structure that efficiently reflects the off-resonance spectral components while
      passing the resonant part. This concept is applied to design multilayer
      transmission bandpass filters with high efficiency, narrow linewidth, symmetrical
      response, and low sidebands.

PMID- 21068925
TI  - Design of diffractive phase elements that produce focal annuli: a new method.
AB  - A new optimization method based on the general theory of amplitude-phase
      retrieval is proposed for designing the diffractive phase elements (DPE's) that
      produce focal annular patterns. A set of equations for determining the phase
      distribution of the DPE is given. The profile of a surface-relief DPE can be
      designed with an iterative algorithm. Numerical calculations are carried out for
      several examples. A comparison of the performance of the DPE's designed with the
      Gerchberg-Saxton algorithm and the new algorithm is presented. The effect of
      quantization of the phase distribution of the DPE's on the results is also
      investigated. The results show that the new algorithm can successfully achieve
      the design of the DPE's that convert the uniform incident beam into the focal
      annular patterns.

PMID- 21068926
TI  - Parallel algorithms and architectures based on pipelined optical buses.
AB  - Optical signals have some unique properties, such as unidirectional propagation
      and precisely predictable path delays in waveguides, which are not shared with
      their electronic counterparts. By taking advantage of these unique properties, we
      can use optical interconnections to achieve speed improvements in single
      instruction stream, multiple-data streams (SIMD) computations. We first show how
      optical buses can be utilized advantageously in SIMD architectures to obtain fast
      solutions to several computational problems, including integer addition, counting
      and logical XOR, sorting, and fast Fourier transforms. We then present a new
      implementation of the optical buses to meet the unique requirements in
      highperformance optical-electronic computing systems. Such an implementation
      allows the transmission of messages at speeds ideal for optics and, in the
      meantime, the processing of data at speeds ideal for electronics, dealing
      successfully with the speed limitation by electronics in optical-electronic
      computers. The primary effects of this bimodal optical bus are twofold: reduction
      of fiber lengths and reduction of system latency. Reduced latency is a unique
      advantage to an optical bimodal bus. Together, these observations make optical
      bus-based architectures appear to be a promising approach to SIMD processing.

PMID- 21068927
TI  - Placement of clock gates in time-of-flight optoelectronic circuits.
AB  - Time-of-flight synchronized optoelectronic circuits capitalize on the highly
      controllable delays of optical waveguides. Circuits have no latches;
      synchronization is achieved by adjustment of the lengths of waveguides that
      connect circuit elements. Clock gating and pulse stretching are used to restore
      timing and power. A functional circuit requires that every feedback loop contain
      at least one clock gate to prevent cumulative timing drift and power loss. A
      designer specifies an ideal circuit, which contains no or very few clock gates.
      To make the circuit functional, we must identify locations in which to place
      clock gates. Because clock gates are expensive, add area, and increase delay, a
      minimal set of locations is desired. We cast this problem in graph-theoretical
      form as the minimum feedback edge set problem and solve it by using an adaptation
      of an algorithm proposed in 1966 [IEEE Trans. Circuit Theory CT-13, 399 (1966)].
      We discuss a computer-aided-design implementation of the algorithm that reduces
      computational complexity and demonstrate it on a set of circuits.

PMID- 21068928
TI  - Holographic switch with a ferroelectric liquid-crystal spatial light modulator
      for a large-scale switch.
AB  - A holographic switch with a ferroelectric liquid-crystal spatial light modulator
      is proposed for large switching systems such as those used in subscriber
      networks. Preliminary experiments have achieved a one-input, 48-output switch.
      The relationship between the power of the control-light source and the number of
      outputs is calculated; the results agree well with the experiment. The
      calculation suggests that 10384-output switching can be obtained with a 25-mW
      control-light source. It should therefore be possible to control a large-scale
      switch with low-power control-light sources.

PMID- 21068929
TI  - Triple-product optical processor for analysis of pulse-repetition and carrier
      frequencies of radar signals.
AB  - A triple-product acousto-optic processor output was studied analytically and
      numerically. The processor is capable of detecting the carrier frequency and the
      modulation envelope of a signal.

PMID- 21068930
TI  - Feature-extracted joint transform correlation.
AB  - A new technique for real-time optical character recognition that uses a joint
      transform correlator is proposed. This technique employs feature-extracted
      patterns for the reference image to detect a wide range of characters in one
      step. The proposed technique significantly enhances the processing speed when
      compared with the presently available joint transform correlator architectures
      and shows feasibility for multichannel joint transform correlation.

PMID- 21068932
TI  - All-optical implementation of a self-organizing map: Learning and taxonomy
      capability assessment.
AB  - We present some experimental results obtained with an all-optical implementation
      of a self-organizing map. The system is based on two ferroelectric liquid
      crystal, bistable optically addressed spatial light modulators (BOASLM's) used as
      parallel read/write optical memories and as thresholding devices. Modifications
      made to adapt the basic algorithm to the BOASLM's are studied in computer
      simulations that predict training-class loss due to the simplified decision stage
      as the principal drawback. Experimental results show good system behavior in
      recognition mode, demonstrating generalization properties and confirming the
      choice of a BOASLM memory. All-optical learning is shown in simple cases, and the
      elementary BOASLM decision function is confirmed as the major limiting factor.
      The ultimate possible system performance is discussed, and ways of overcoming
      present limits are suggested.

PMID- 21068931
TI  - Analysis of the dual discrimination ability of the two-port photorefractive joint
      transform correlator.
AB  - An all-optical joint transform correlator featuring two operative correlation
      planes(ports) with complementary performance is presented. We present the theory
      of operation, derive the input-output characteristics, and demonstrate computer
      simulations and experimental results. The two-port joint transform correlator is
      based on simultaneous use of two photorefractive wave-mixing architectures. The
      first port uses two-beam coupling, and the second port uses four-wave mixing. The
      performance of the two ports depends on an experimentally controlled beam
      intensity ratio and the photorefractive coupling coefficient. With appropriate
      selection of these parameters, the first port is capable of high discrimination,
      while simultaneously the second offers a low discrimination output. Our results
      show that the two-beam coupling port can achieve peak-to-noise and signal-to
      noise ratio values better than the phase-only correlator, whereas the four-wave
      mixing port performs similarly to the classical joint transform correlator. This
      leads to a potential application in which the correlator could be set up so that
      in one port a general class is detected (interclass) and, in the other, the
      specific item in a class is detected (intraclass).

PMID- 21068933
TI  - Cantor network, control algorithm, two-dimensional compact structure and its
      optical implementation.
AB  - A compact integrating module technique for packaging a optical multistage Cantor
      network with a polarization multiplex technique is suggested. The modules have a
      unique configuration, which is the solid-state combination of a polarization
      rotator, double birefringent slabs, and a 2 * 2 switch array. The design and the
      fabrication of an eight-channel optical nonblocking Cantor network are
      demonstrated, and a fast-setup control algorithm is developed. The network
      systems are easy to assemble and insensitive to environment disturbance.

PMID- 21068934
TI  - Error-correction schemes for volume optical memories.
AB  - An optically addressed Reed-Solomon parallel decoder has been designed and
      fabricated for onedimensional parallel access optical memories. The [15, 9] Reed
      Solomon decoder operates on 60 parallel optical inputs and has been demonstrated
      at a data rate of 300 megabits/s. Compared with equivalent serial decoding
      solutions, this decoder is shown to be more area efficient and offers reduced
      latency. An extension to two-dimensional error correction using both the parallel
      and serial strategies is presented, and comparisons are made in terms of
      parallelism, page rate, and information rate for the two architectures. A hybrid
      optoelectronic decoding architecture that uses optical finite-field matrix-vector
      multipliers is given and is shown to offer error correction at large block sizes
      and aggregate data rates exceeding 10(12) bits/s.

PMID- 21068935
TI  - Dependence of the tracking performance of an optical disk on the direction of the
      incident-light polarization.
AB  - In optical-disk data-storage systems, the signal that provides tracking
      information is dependent on the groove shape, the optical constants of the
      materials involved, and the polarization state of the incident light. In this
      paper, we show that the tracking signal can be described by two measurable
      quantities, both of which are largely independent of aberrations in the optical
      system. Using these two quantities, we match the tracking performance of a given
      disk to an equivalent disk having rectangular grooves-the adjustable parameters
      being the rectangular groove depth and the duty cycle. By assumption, these
      rectangular grooves modulate only the phase of the incident beam and disregard
      its state of polarization. The effective groove depth and the duty cycle thus
      become dependent on the polarization state of the incident beam. We examine these
      dependences for various disks having different groove geometries and different
      combinations of materials.

PMID- 21068936
TI  - Rewritable optical-disk fabrication with an optical recording material made of
      naphthalocyanine and polythiophene.
AB  - A novel rewritable optical disk that uses an optical recording material made of
      naphthalocyanine and polythiophene as the recording layer is described. In this
      system the complex refractive index of the recording material changes reversibly,
      depending on the aggregation states of naphthalocyanine induced by a conformation
      change of the polythiophene matrix. After recording, the imaginary part of the
      refractive index of the recording material increases to three times that of the
      unrecorded part, at a wavelength of 790 nm at which a semiconductor laser emits
      light. The fabricated polythiophene naphthalocyanine optical disk shows a high
      reflectivity of 58% and a large readout modulation amplitude (I(11)/I(top)) of
      0.63. It is confirmed that the polythiophene/naphthalocyanine optical disk can be
      played back on conventional compact-disc players even after ten cycles of
      rewriting.

PMID- 21068937
TI  - White-light implementation of the Wigner-distribution function with an achromatic
      processor.
AB  - A temporally incoherent optical processor that combines diffractive and
      refractive components is proposed for performing two different operations
      simultaneously: an achromatic image along an axis and an achromatic one
      dimensional Fourier transformation along the orthogonal axis. These properties
      are properly employed to achieve the achromatic white-light display of the Wigner
      distribution function associated with a one-dimensional real signal, with high
      redundancy and variable scale.

PMID- 21068938
TI  - Two-dimensional wavelet transform achieved by computer-generated multireference
      matched filter and Dammann grating.
AB  - A two-dimensional wavelet transform is optically performed in real time by use of
      a new multichannel system that processes the different daughter wavelets
      separately. The system, which is able to handle every wavelet function, relies on
      a Dammann grating for generating a multichannel array. All channels are processed
      in parallel by a conventional two-dimensional correlator. Experimental results
      applying Morlet-wavelet decomposition are presented.

PMID- 21068939
TI  - Photorefractive beam-steering system that uses energy transfer in a BaTiO(3)
      crystal for a fiber-array interconnect.
AB  - A beam-control system to write gratings on a holographic plane is studied. The
      arrangement is designed to interconnect two 1024 monomode fiber arrays. The beam
      control system is composed of two subsystems: a beam steerer, which deflects one
      incident beam toward 1024 positions, and a collimating system, which adapts the
      shape of the deflected beam to the holographic plane. The collimating system was
      studied only after the beam steerer had been fully built and tested. It is based
      on the photorefractive amplification of a beamlet selected by a shutter array.
      The deflection efficiency is enhanced by a factor 1500 with the photorefractive
      crystal, and the signal-to-noise ratio is larger than 5500. The influence of the
      optical aberrations on the coupling losses of the infrared beams in the monomode
      fibers are evaluated.

PMID- 21068940
TI  - Optically tunable optical filter.
AB  - We experimentally demonstrate an optically tunable optical filter that uses
      photorefractive barium titanate. With our filter we implement a spectrum analyzer
      at 632.8 nm with a resolution of 1.2 nm. We simulate a wavelength-division
      multiplexing system by separating two semiconductor laser diodes, at 1560 nm and
      1578 nm, with the same filter. The filter has a bandwidth of 6.9 nm. We also use
      the same filter to take 2.5-nm-wide slices out of a 20-nm-wide superluminescent
      diode centered at 840 nm. As a result, we experimentally demonstrate a phenomenal
      tuning range from 632.8 to 1578 nm with a single filtering device.

PMID- 21068941
TI  - Entropy-based definition of laser beam spot size.
AB  - We introduce new definitions of spot size, mean curvature radius, divergence
      angle, and quality of laser beams that are based on Shannon's information-entropy
      formula and study their properties.

PMID- 21068942
TI  - Phase locking of CO(2) lasers by the use of diffraction effects.
AB  - A technique to phase lock CO(2) lasers with spatially separated active media was
      investigated. Only reflective optics (except for the output coupler) were used,
      in view of applications of this method in the field of high-power lasers. Phase
      locking was established when the beams of two resonator branches were made to
      propagate very close to each other along the so-called coupling path. As a result
      of diffraction effects both resonators were exchanging energy, establishing a
      phase-locked operation mode when several locking conditions were fulfilled. A
      maximum coupling coefficient (the ratio between the diffracted intensity in the
      second cavity and the intercavity intensity in the first resonator) of 2.6% could
      be achieved. Because phase locking was highly dependent on the difference between
      the two resonator lengths, a length control that uses a piezoelectric translator
      connected to one of the resonator mirrors was used. To detect phase locking, the
      intensity maximum of the interference pattern of the two laser beams was
      monitored with a fast detector. By application of a ramp signal to the
      piezoelectric translator and detection of the peak intensity, the locking range
      could be measured. Up to a mismatch of the resonator lengths of lambda/130,
      locking could be maintained. The measurements were compared with results of a
      computer simulation with Huygens-Fresnel integrals to describe diffraction and
      the one-dimensional Maxwellian equations to calculate supermodes and to analyze
      their stability. The numerical results showed an excellent agreement with the
      measured values.

PMID- 21068943
TI  - Comparison of laser performance of dye molecules in sol-gel, polycom, ormosil,
      and poly(methyl methacrylate) host media.
AB  - Laser performance is described for Rhodamine 590, Pyrromethene 567, Perylene red,
      and Perylene orange in inorganic porous sol-gel glass, poly(methyl
      methacrylate)(PMMA), a composite of porous sol-gel glass with PMMA and
      organically modified silicate ormosil glass. Lasers were excited with a flash
      lamp-pumped dye laser in the long-pulse-length regime (3 us, 506 nm, 300 mJ) and
      a second-harmonic Nd:YAG laser in the short-pulse-length regime (6 or 15 ns, 532
      nm, 60 mJ). The feasibility of long-pulse-length operation is demonstrated,
      detailed characteristics of short-pulse operation are described, and laser damage
      measurements are given. The nonpolar perylene dyes had better performance in
      partially organic hosts, and the ionic rhodamine and pyrromethene dyes performed
      best in the inorganic sol-gel glass host.

PMID- 21068944
TI  - Room-temperature 1.643-um Er(3+):Y(3)Sc(2)Ga(3)O(12) (Er:YSGG) laser.
AB  - Laser operation at 1.643 um ((4)I(13/2)-(4)I(15/2)) in Er(3+):Y(3)Sc(2)Ga(3)O(12)
      (Er:YSGG) at 300 K is reported. An Er:glass laser (1.532 um) was used in an end
      pumping arrangement to obtain laser output from a 1-cm-long 0.7% Er(3% Yb, 1%
      Cr):YSGG crystal in an external cavity. The Er:YSGG laser exhibited an 18-mJ
      threshold and a 10% slope efficiency.

PMID- 21068945
TI  - Determination of the second-order susceptibility of ammonium dihydrogen phosphate
      and alpha-quartz at 633 and 1064 nm.
AB  - The second-order susceptibility d(36) of ammonium dihydrogen phosphate (ADP) was
      determined from phase-matched second-harmonic generation (SHG) at two
      wavelengths. A cw single-mode He-Ne laser (lambda= 633 nm) and a cw single-mode
      Nd:YAG laser (lambda= 1064 nm) were used as fundamental beam sources. The results
      were d(36)(ADP, 633 nm) =(1.31 +/- 0.05) *10(-9) esu = 0.55 +/- 0.02 pm/V and
      d(36)(ADP, 1064 nm) = (1.10 +/- 0.06) * 10(-9) esu = 0.46 +/- 0.03 pm/V. The
      d(11) values of alpha-quartz were determined relative to d(36)(ADP) to be
      d(11)(alpha-quartz, 633 nm) = (7.4 +/- 0.3) * 10(-10) esu = 0.31 +/- 0.01 pm/V
      and d(11)(alpha-quartz, 1064 nm) = (7.1 +/- 0.3) * 10(-10) esu = 0.30 +/- 0.01
      pm/V by the use of the Maker fringe method. The Miller's delta ofADP and alpha
      quartz is in good agreement at the two wavelengths.

PMID- 21068946
TI  - Technique for stabilizing the phase of the reference signals in analog fiber
      optic links.
AB  - The effects of temperature and longitudinal stress on the phase delay of
      reference signals in a fiber-optic link are discussed. A feedback system that
      uses a fiber-optic phase modulator is used to compensate for the phase
      fluctuations of a reference signal in the link. The phase deviations of a 50-MHz
      reference frequency that are caused by temperature variations of the link is
      reduced by more than 95% on optimization of the correction system. The advantages
      of this technique are that the fiber-optic phase modulator has a greater
      stability compared with the electronic phase modulators, and signal conversions
      from electric to optic and optic to electric are avoided.

PMID- 21068947
TI  - Effect of external index of refraction on multimode fiber couplers.
AB  - <p>The dependence of the performance of fused-taper multimode fiber couplers on
      the refractive index of the material surrounding the taper region has been
      investigated both theoretically and experimentally. It has been identified that
      for a 2 * 2 multimode fiber coupler there is a range of output-power-coupling
      ratios for which the effect of the external refractive index is negligible. When
      the coupler is tapered beyond this region, the performance becomes dependent on
      the external index of refraction and lossy. To analyze the multimode coupler-loss
      mechanism, we develop a two-dimensional ray-optics model that incorporates
      trapped cladding-mode loss and core-mode loss through frustrated total internal
      reflection.</p><p>Computer-simulation results support the experimental
      observations. Related issues such as coupler fabrication and packaging are also
      discussed.</p>

PMID- 21068948
TI  - Millimeter-wave filters with laser control in waveguides.
AB  - A detailed analysis of a microwave reflection pattern that is due to periodically
      photoexcited layers of semiconductor material in a waveguide is presented.
      Different photoconductivity profiles that are due to different excitation
      conditions with different materials are tested. The diffusion of carriers in the
      direction of propagation can strongly affect the passband-filtering responses,
      especially the efficiency and the bandwidth. These configurations can be used as
      light-induced tunable filters and as a variable matching section between
      different levels of impedances.

PMID- 21068949
TI  - Resonant-cavity-enhanced thin-film AlGaAs/GaAs/AlGaAs LED's with metal mirrors.
AB  - Resonant-cavity-enhanced light-emitting diodes (RCE LED's) are of increasing
      interest as a low-cost alternative to lasers for short-distance applications. We
      report on the characteristics of thin-film AlGaAs/GaAs/AlGaAs double
      heterostructure RCE LED's with metal mirrors on both sides fabricated by means of
      epitaxial liftoff and bonded to silicon host substrates. The devices exhibit
      typical turn-on voltages of 1.3 V, operating resistances of 31 Omega, linewidths
      of 10.4 nm, efficiencies of 1.4%, dispersion half-angles of 23.7 degrees , and
      stable output over more than 1700 h. These devices exhibit significant
      improvement over conventional LED's without additional complicated processing or
      growth steps, resulting in a manufacturable, low-cost device.

PMID- 21068950
TI  - Electronic subtracter for trace-gas detection with InGaAsP diode lasers.
AB  - An electronic noise-cancellation scheme has been developed and tested for second
      harmonic (2f) detection with short-external-cavity and distributed-feedback
      InGaAsP diode lasers and wavelength modulation. The 2f background signal and
      noise from, e.g., optical feedback, optical fringes, and power-supply pickup are
      effectively reduced by subtraction of a measure of the signal-beam photocurrent
      from a measure of the reference-beam photocurrent. The dynamic range required for
      the lock-in amplifier is also reduced because the signal owing to modulation of
      the laser output at the first harmonic is canceled. Reduction of the 2f
      background and dynamic range are important for atmospheric-pressure detection
      where a large wavelength modulation is necessary. The detector noise was
      minimized by the use of zero-biased detectors in the subtraction circuit. A beam
      noise level (defined as 2* the rms value) equivalent to a line-center absorption
      of 1.6 * 10(-6) was achieved with an equivalent-noise bandwidth of 1.25 Hz for 2f
      detection at 10 kHz. The electronic circuit is easy to construct and low cost.

PMID- 21068951
TI  - Effect of molecular anisotropy on backscattered ultraviolet radiance.
AB  - The effect of molecular anisotropy on backscattered UV (BUV) radiances is
      computed by accounting for it in both Rayleigh optical thickness and the
      scattering-phase matrix. If the effect of molecular anisotropy is included only
      in the optical thickness and not in the phase matrix, then for high sun (theta(0)
      ~ 0 degrees ), the nadir radiance (I(0)) leaving the top of the atmosphere is
      approximately 1.8% higher than the radiance (I(op)) computed with the effect
      included in the phase matrix. For very low sun (theta(0) > 80 degrees ), I(0) is
      approximately 2.3% lower than I(op). For off-nadir radiances the relative
      increase (decrease) depends on both the local zenith angle as well as the azimuth
      angle. Also, an increase in the surface reflectivity decreases the effect of
      molecular anisotropy on the upwelling radiances. Exclusion of the anisotropy
      factor in the Rayleigh-phase matrix has very little effect (<1%) on ozone
      retrieval from the BUV-type instruments. This is because of the ratio technique
      used in the retrieval algorithm, which practically cancels out the anisotropy
      effect.

PMID- 21068952
TI  - Determination of stratospheric aerosol microphysical properties from independent
      extinction and backscattering measurements with a Raman lidar.
AB  - An algorithm that permits the retrieval of profiles of particle mass and surface
      area concentrations in the stratospheric aerosol layer from independently
      measured aerosol (particle and Rayleigh) and molecule (Raman or Rayleigh)
      backscatter signals is developed. The determination is based on simultaneously
      obtained particle extinction and backscatter profiles and on relations between
      optical and microphysical properties found from Mie-scattering calculations for
      realistic stratospheric particle size distributions. The size distributions were
      measured with particle counters released on balloons from Laramie, Wyoming,
      between June 1991 and April 1994. Mass and surface-area concentrations can be
      retrieved with relative errors of 10-20% and 20-40%, respectively, with a laser
      wavelength of 355 nm and with errors of 20-30% and 30-60%, respectively, with a
      laser wavelength of 308 nm. Lidar measurements taken within the first three years
      after the eruption of Mt. Pinatubo in June 1991 are shown. Surface-area
      concentrations around 20 um(2) cm(-3) and mass concentrations of 3 to 6 ug m(-3)
      were found until spring 1993.

PMID- 21068953
TI  - Identification and correction of analog-to-digital-converter nonlinearities and
      their implications for differential absorption lidar measurements.
AB  - Differential absorption lidar (DIAL) is a powerful remote-sensing technique
      widely used to probe the spatial and temporal distribution of ozone and other
      gaseous atmospheric trace constituents. Although conceptually simple, the DIAL
      technique presents many challenging and often subtle technical difficulties that
      can limit its useful range and accuracy. One potentially serious source of error
      for many DIAL experiments is nonlinearity in the analog-to-digital converters
      used to capture lidar return signals. The impact of digitizer nonlinearity on
      DIAL measurements is examined, and a simple and inexpensive low-frequency
      dithering technique that significantly reduces the effects of ADC nonlinearity in
      DIAL and other applications in which the signal is repetitively averaged is
      described.

PMID- 21068954
TI  - Comparative precision of distributed-backscatter Doppler lidars.
AB  - Simple formulas for the standard deviation that is available from Doppler
      velocity estimators through the use of direct-detection frequency discriminators
      for targets spread in range are derived and contrasted with the fundamental
      limits provided by the Cramer-Rao bounds for both direct-detection and heterodyne
      systems. The structures of these formulas is sufficiently similar to facilitate a
      meaningful comparison among the different systems and to provide a basis for the
      evaluation of experimental performance.

PMID- 21068955
TI  - Proposal for the measurement of backward and total scattering by mineral
      particles suspended in water.
AB  - An experimental procedure for the determination of the specific backscattering
      and total scattering coefficients of mineral particles suspended in water is
      described. The procedure combines measurements performed on samples of particles
      retained in glass-fiber filters and suspended in water, using a dual-beam
      spectrophotometer provided with an integrating-sphere attachment.

PMID- 21068956
TI  - Island perturbation to the sky radiance over the ocean: simulations.
AB  - Sky-radiance measurements at the sea surface can be used to estimate radiative
      properties of aerosols over water. We demonstrate, through Monte Carlo
      simulations, that significant perturbations to sky radiance over the ocean can
      occur when measurements are carried out with radiometers located on islands. In
      particular, we present examples of the influence of the physical and optical
      thicknesses of an aerosol layer, the azimuth of observation relative to the Sun,
      the size of the island, the location of the radiometer on the island, and the
      albedo of the island on the magnitude of the perturbation for a circular island
      of uniform albedo. Relative errors in sky radiance of as high as 39% were found
      in the blue. Simulated (perturbed) sky radiances were combined with an algorithm
      for retrieving the aerosol phase function P(theta), where theta is the scattering
      angle, and with the single-scattering albedo omega(0), to demonstrate how the
      perturbation can influence the retrieved values. It was found that the fractional
      error in the retrieved values of the product omega(0)P(theta) can be
      significantly greater than the fractional error in the sky radiance, because of
      the effects of multiple scattering. This underscores the importance of removing
      the island perturbation before an inversion algorithm is used. A first-order
      procedure for removing the island perturbation based on the values of
      omega(0)P(theta) retrieved from the perturbed sky radiance is proposed and is
      found to be effective if the island perturbation is not too large. A simplified
      Monte Carlo procedure that is applicable to an island of arbitrary shape and
      albedo distribution is presented. The procedure could be used to assess the
      suitability of a given island as a measurement site, and to provide a first-order
      correction to actual experimental measurements.

PMID- 21068957
TI  - Remote sensing of ocean color: a methodology for dealing with broad spectral
      bands and significant out-of-band response.
AB  - A methodology for delineating the influence of finite spectral bandwidths and
      significant out-of-band response of sensors for remote sensing of ocean color is
      developed and applied to the Sea-viewing Wide-Field-of-view Sensor (SeaWiFS). The
      basis of the method is the application of the sensor's spectral-response
      functions to the individual components of the top-of-the-atmosphere (TOA)
      radiance rather than the TOA radiance itself. For engineering purposes, this
      approach allows one to assess easily (and quantitatively) the potential of a
      particular sensor design for meeting the system-sensor plus algorithms
      performance requirements. In the case of the SeaWiFS, two significant conclusions
      are reached. First, it is found that the out-of-band effects on the water-leaving
      radiance component of the TOA radiance are of the order of a few percent compared
      with a sensor with narrow spectral response. This implies that verification that
      the SeaWiFS system-sensor plus algorithms-meets the goal of providing the water
      leaving radiance in the blue in clear ocean water to within 5% will require
      measurements of the water-leaving radiance over the entire visible spectrum as
      opposed to just narrow-band (10-20-nm) measurements in the blue. Second, it is
      found that the atmospheric correction of the SeaWiFS can be degraded by the
      influence of water-vapor absorption in the shoulders of the atmospheric
      correction bands in the near infrared. This absorption causes an apparent
      spectral variation of the aerosol component between these two bands that will be
      uncharacteristic of the actual aerosol present, leading to an error in
      correction. This effect is dependent on the water-vapor content of the
      atmosphere. At typical water-vapor concentrations the error is larger for
      aerosols with a weak spectral variation in reflectance than for those that
      display a strong spectral variation. If the water-vapor content is known, a
      simple procedure is provided to remove the degradation of the atmospheric
      correction. Uncertainty in the water-vapor content will limit the accuracy of the
      SeaWiFS correction algorithm.

PMID- 21068958
TI  - Simplex method in problems of light-beam phase control.
AB  - The possibility of the application of the simplex method to problems of wave
      front control for light beams propagating in a nonlinear medium is investigated.
      A numerical analysis of simplex-method effectiveness in comparison with the
      gradient procedure of hill climbing is carried out. The regimes of stationary and
      nonstationary wind refraction are considered. The simplest optimization of the
      simplex size and the control basis is done.

PMID- 21068959
TI  - Observations of thermospheric wind velocities and temperatures by the use of a
      Fabry-Perot Doppler imaging system at Syowa Station, Antarctica.
AB  - A new optical instrument, the Fabry-Perot Doppler imaging system (FPDIS), has
      been developed for observations of two-dimensional distributions of thermospheric
      wind velocities and temperatures by the measurement of the Doppler shift and
      width of the aurora or of the airglow emission lines of atomic oxygen OI 557.7 nm
      and OI 630.0 nm over a wide field of view (165 degrees ). A technique for the
      derivation of Doppler temperatures and wind velocities was developed by use of a
      truncated Fourier series. Thermospheric wind velocities and temperatures have
      been obtained with unprecedented high temporal (1 min) and spatial (24 points for
      an all-sky image) resolutions. Errors in the derived wind velocities and
      temperatures are estimated to be less than 25 m/s and 100 K, respectively, for
      inner-fringe positions and 35 m/s and 170 K for outer-fringe positions,
      respectively. This system was applied to observations of thermospheric wind
      velocities and temperatures at Syowa Station (69.00 degrees  S, 39.58 degrees 
      E), Antarctica for the period of one austral winter in 1990.

PMID- 21068960
TI  - Atmospheric transmittance of an absorbing gas. 5. Improvements to the OPTRAN
      approach.
AB  - Improvements to a fast and accurate transmittance-calculation procedure, Optical
      Path TRANsmittance (OPTRAN), are described. The previous version computed a
      transmittance ratio for an absorbing layer. It required special attention to the
      interpolation methodology. The new approach reported here computes the absorption
      coefficient for an absorbing layer. This modified approach is not only simpler
      but also runs in one twentieth the time of the original OPTRAN approach with the
      same accuracy.

PMID- 21068961
TI  - Analysis of pollutant chemistry in combustion by in situ pulsed photoacoustic
      laser diagnostics.
AB  - A technique for gas analysis based on pulsed-laser-induced photoacoustic
      spectroscopy in the UV and the visible is presented. The laser-based technique
      and the associated analysis probe have been developed for the analysis of
      pollutant chemistry in fluidized beds and other combustion environments with
      limited or no optical access. The photoacoustic-absorption spectrum of the
      analyzed gas is measured in a test cell located at the end of a tubular probe.
      This test cell is subject to the prevailing temperature and pressure in the
      combustion process. The instrument response has been calibrated for N(2)O, NO,
      NO(2), NH(3), SO(2), and H(2)S at atmospheric pressure between 20 and 910 
      degrees C. The response of the probe was found to increase with pressure for
      N(2)O, NO, NH(3), and NO(2) up to 1.2 MPa pressure. The method and the probe have
      been used for detection and ranging of gas concentrations in a premixed methane
      flame. Some preliminary tests in a large 12-MW circulating bed boiler have also
      been done.

PMID- 21068962
TI  - Interferometric laser imaging for droplet sizing: a method for droplet-size
      measurement in sparse spray systems.
AB  - A full-field, time-resolved interferometric method for the characterization of
      sparse, polydisperse spray systems is reported. The method makes use of the
      angular intensity oscillations in the wide-angle forward-scatter region. A pulsed
      laser is used to illuminate a planar sheet through the spray, which is imaged,
      out of focus, from the 45 degrees direction. The image consists of a set of out
      of-focus spots, each of which represents an individual droplet, and superimposed
      on which is a set of fringes corresponding to the angular intensity oscillations
      of that droplet. Macrophotographic recording with high-resolution digitization
      for image analysis provides a full-field capability. The spatial frequency of
      fringes on each spot in the image plane is dependent on the diameter of the
      corresponding droplet in the object plane, and a simple geometric analysis is
      shown to be appropriate for the calculation of the spatial frequency of fringes
      as a function of droplet size. Images are analyzed automatically by a software
      suite that uses Gaussian blur, Canny edge detection, and Hough transforms to
      locate individual droplets in the image field. Fringe spatial frequency is then
      determined by least-squares fitting to a Chirp function. The method is applicable
      to droplets with diameters in the range of several millimeters to several hundred
      millimeters and number densities of up to 10(3) to 10(4). The accuracy of the
      method for droplet-size determination has been evaluated by measurements of
      monodisperse aerosols of known droplet size, and measurements of droplet-size
      distribution in a polydisperse aerosol produced by a gasoline fuel injector are
      also presented. An extension of the method, using high-speed photography to
      measure two components of velocity in addition to size and position, is
      discussed. A two-wavelength approach may also offer the capability to measure the
      concentration of model fuel additives in droplets, and the results of a
      feasibility study are described.

PMID- 21068963
TI  - Improved technique for data inversion: optical sizing of multicomponent aerosols.
AB  - Estimation of particle-size distribution is analyzed for the complicated case of
      compound aerosols, in which particles are distinguished by sizes and optical
      constants. This task arises in a number of interesting practical situations when
      aerosol scatterers cannot be described with a common refractive index. This is an
      inverse problem with a large number of variables, and questions of formal
      inversion are of great importance here. They are discussed in detail, and an
      improved numerical-inversion method is proposed. The method provides a
      nonnegative and highly stable solution and makes it possible to include varied
      additional or a priori information. It is shown that the proposed technique is
      closely related to well-known linear and relaxation methods widely used in
      atmospheric optics. The algorithm for determination of bicomponent aerosol-size
      distribution is devised. It uses the intensity of light scattered at different
      angles and spectral-extinction measurements. In addition, the algorithm can
      incorporate a priori restrictions of size-spectra smoothness. A set of numerical
      examples illustrates the algorithm.

PMID- 21068964
TI  - Simplex deconvolutions of particle-size distribution functions from optical
      measurements.
AB  - The use of the downhill simplex technique is presented for the deconvolution of
      particle-size distribution functions from optical-scattering and optical
      extinction measurements. Criteria are developed for the assessment of the
      goodness of fit, and the stabilities of the simplex and the linear-inversion
      methods are compared. Monte Carlo simulations of synthetic data are used with
      various random-error levels to demonstrate and to compare the deconvolution
      results of log-normal distributions from scattering and extinction measurements.

PMID- 21068965
TI  - Validity of weak-scattering models in forward two-dimensional optical scattering.
AB  - The exact solution for scattering from cylindrical objects is compared with the
      following weak-scattering models: the first Born approximation, the Rytov
      approximation, the straight-ray model of geometric optics, and ray tracing.
      Computer calculations of the various approximate and the exact virtual fields at
      the center of a transparent cylinder are compared in order to find the practical
      limitations of the various approximations with respect to cylinder radii and
      indices of refraction. It is found that the Rytov approximation introduces a
      phase error that increases linearly with the cylinder radius. The straightray
      model yields better results than the first Rytov approximation for all cylinder
      radii and real indices of refraction, even at the edges. The first Born
      approximation is best for cylinders with radii less than a wavelength.

PMID- 21068966
TI  - Finite-element algorithm for radiative transfer in vertically inhomogeneous
      media: numerical scheme and applications.
AB  - The recently developed finite-element method for solution of the radiative
      transfer equation has been extended to compute the full azimuthal dependence of
      the radiance in a vertically inhomogeneous plane-parallel medium. The physical
      processes that are included in the algorithm are multiple scattering and bottom
      boundary bidirectional reflectivity. The incident radiation is a parallel flux on
      the top boundary that is characteristic for illumination of the atmosphere by the
      Sun in the UV, visible, and near-infrared regions of the electromagnetic
      spectrum. The theoretical basis is presented together with a number of
      applications to realistic atmospheres. The method is shown to be accurate even
      with a low number of grid points for most of the considered situations. The
      FORTRAN code for this algorithm is developed and is available for applications.

PMID- 21068967
TI  - Internal and near-surface electromagnetic fields for an absorbing spheroidal
      particle with arbitrary illumination.
AB  - A previously developed [Appl. Opt. 34, 5542 (1995)] theoretical procedure for the
      calculation of the internal and the near-surface electromagnetic fields for
      nonabsorbing spheroidal particles with arbitrary monochromatic illumination has
      been generalized to permit solutions for absorbing (i.e., complex relative index
      of refraction) spheroidal particles. Calculations are presented that demonstrate
      the general effects of absorption on the internal and near-surface
      electromagnetic-field distributions for the particular case of a plane wave that
      is incident upon a 2:1-axis-ratio oblate spheroidal particle.

PMID- 21068968
TI  - Provision of exact formulations for the "forward scattering of a Gaussian beam by
      a nonabsorbing sphere": comment.
AB  - The purpose of an earlier publication [Appl. Opt. 34, 2120 (1995)], to provide an
      exact formulation of the scattering of beamlike radiation fields from spheres, is
      clarified and its relation to the treatment of this subject in two more recent
      publications is described. Also, an error in the reference list in the earlier
      publication is rectified.

PMID- 21068969
TI  - Analog measurement of scattered optical fluctuations.
AB  - Astatistical model that describes the analog measurement of a fluctuating light
      intensity that arises from a non-Gaussian scattering process is developed. The
      higher-order statistical moments are derived for a p-i-n diode receiver model and
      gamma-distributed intensity fluctuations. Criteria for the accurate measurement
      of the scattering fluctuations are found, and these are used to analyze data
      derived from an on-line scatterometer system. Implications for future on-line
      measurement technology are discussed.

PMID- 21068970
TI  - Patents.
AB  - 5,341,240; 5,402,227; 5,404,869; 5,406,089; 5,414,560; 5,416,326; 5,418,866;
      5,418,866; 5,425,124; 5,428,472; 5,428,475; 5,430,561.

PMID- 21068971
TI  - Simple analytical model of bias dependence of the photocurrent of metal
      semiconductor-metal photodetectors.
AB  - The current-voltage (I-V) characteristics of metal-semiconductor-metal (MSM)
      photodetectors under various light intensities are examined. The current shows an
      initial increase followed by saturation and a subsequent sharp increase as bias
      increases. We propose a theoretical model for bias dependence in all regions of
      operation except for breakdown, based on drift collection of carriers in the
      depleted regions under the contacts and diffusion and recombination in the
      undepleted region. This is based on the solution of the diffusion equation in the
      undepleted area between the two contacts of the MSM structure. The solution is
      subject to boundary conditions on excess minority carriers at the cathode end and
      continuity of current at the anode end. The latter is written in terms of a
      parameter, denoted as effective diffusion length, which describes the collection
      efficiency of carriers at the anode. The closed-form solution thus derived
      corroborates with physical expectations in several limiting cases. To compare
      theory with experiment, we propose methods to extract parameters that are used to
      normalize the I-V curves and calculate depletion widths under different light
      intensities, from current- and capacitance-voltage measurements. A close match
      between experimental and theoretical results is observed, and possible breakdown
      mechanisms are discussed.

PMID- 21068972
TI  - Focal switch: a new effect in low-Fresnel-number systems.
AB  - It is shown for the first time we believe, that when a spherical wave illuminates
      a certain type of diffracting screen, in addition to the expected focal-shift
      effect, depending on the value of the Fresnel number of the focusing system, a
      focal switch effect can appear, i.e., an increase in the height of the lateral
      lobe of the axial-intensity distribution over that of the central lobe.

PMID- 21068973
TI  - Large radial graded-index polymer.
AB  - A very large radial graded-index (GRIN) polymer was successfully prepared for the
      first time, to the best of our knowledge, by two methods: the curved mold method
      and the diffusion copolymerization method. Both methods gave a radial GRIN
      polymer with a diameter of 70 mm and a ?n value greater than 0.02. Ray tracing
      through these radial GRIN polymers was used to predict that such a GRIN polymer
      could be a promising candidate for thinner ophthalmic lenses with no spherical
      aberration or multifocusing characteristics.

PMID- 21068974
TI  - Design of a holographic optical element for a pulse compressor.
AB  - Nonlinear chirped pulse compression can be theoretically achieved to any order by
      using a nonplane grating with adequate groove spacing. We evaluate the
      holographic recording of a grating that compensates to the quadratic chirp. A
      suitable design is found, and the building tolerances are analyzed.

PMID- 21068975
TI  - Experimental study of the effect of surface defects on the finesse and contrast
      of a Fabry-Perot interferometer.
AB  - While investigating the instrumental function of a Fabry-Perot interferometer
      [Appl. Opt. 34, 58 (1995), we noticed some variation in finesse and contrast in
      the measured spectra when a 1.5-mm-diameter aperture was used at various spots
      within the standard 8-mm aperture. By comparing experimentally determined finesse
      versus contrast plots for many such spectra with calculated plots, we found spots
      on the plates that gave non-Airy-function line shapes over the entire order of
      interference, unlike the Airy line shape we determined previously by using the
      entire 8-mm aperture. We have reviewed several models that describe the effects
      of various types of surface defects, such as Gaussian-height distribution of
      roughness, curvature and tilt of plates, sinusoidal roughness, and asymmetrical
      roughness on the finesse and contrast. Our experimental results can be accounted
      for if we assume that the reflectivity is nonuniform over the Fabry-Perot plates
      and that there is some reasonable contribution that is due to Gaussian roughness,
      curvature, or tilt.

PMID- 21068976
TI  - Design of algorithms for phase measurements by the use of phase stepping.
AB  - If the best phase measurements are to be achieved, phase-stepping methods need
      algorithms that are 112 insensitive to the harmonic content of the sampled
      waveform and 122 insensitive to phase-shift miscalibration. A method is proposed
      that permits the derivation of algorithms that satisfy both requirements, up to
      any arbitrary order. It is based on a one-to-one correspondence between an
      algorithm and a polynomial. Simple rules are given to permit the generation of
      the polynomial that corresponds to the algorithm having the prescribed
      properties. These rules deal with the location and multiplicity of the roots of
      the polynomial. As a consequence, it can be calculated from the expansion of the
      products of monomials involving the roots. Novel algorithms are proposed, e.g., a
      six-sample one to eliminate the effects of the second harmonic and a 10-sample
      one to eliminate the effects of harmonics up to the fourth order. Finally, the
      general form of a self-calibrating algorithm that is insensitive to harmonics up
      to an arbitrary order is given.

PMID- 21068977
TI  - Phase error calculation in a Fizeau interferometer by Fourier expansion of the
      intensity profile.
AB  - The spectrum of the intensity profile of multiple-beam Fizeau interferograms is
      presented. Knowledge of this spectrum provides valuable information about the
      characteristics of Fizeau interferograms, allowing one to calculate the phase
      error when the Fizeau profile is evaluated by means of two-beam phase-stepping
      algorithms, as is usual for low-reflectivity coefficients.

PMID- 21068978
TI  - Theory of equidistant three-dimensional radiance measurements with optical
      microprobes.
AB  - Fiber-optic radiance microprobes, increasingly applied for measurements of
      internal light fields in living tissues, provide three-dimensional radiance
      distribution solids and radiant energy fluence rates at different depths of
      turbid samples. These data are, however, distorted because of an inherent feature
      of optical fibers: nonuniform angular sensitivity. Because of this property a
      radiance microprobe during a single measurement partly underestimates light from
      the envisaged direction and partly senses light from other directions. A theory
      of three-dimensional equidistant radiance measurements has been developed that
      provides correction for this instrumental error using the independently obtained
      function of the angular sensitivity of the microprobe. For the first time, as far
      as we know, the measurements performed with different radiance microprobes are
      comparable. An example of application is presented. The limitations of this
      theory and the prospects for this approach are discussed.

PMID- 21068979
TI  - Wavelengths of spectral lines in mercury pencil lamps.
AB  - The wavelengths of 19 spectral lines in the region 253-579 nm emitted by Hg
      pencil-type lamps were measured by Fourier-transform spectroscopy. Precise
      calibration of the spectra was obtained with wavelengths of (198)Hg as external
      standards. Our recommended values should be useful aswavelength-calibration
      standards for moderate-resolution spectrometers at an uncertainty level of 0.0001
      nm.

PMID- 21068980
TI  - Irradiances of spectral lines in mercury pencil lamps.
AB  - The irradiancesof 37 spectral lines emitted bymercury pencil-type lamps were
      measuredby comparison with calibrated continuum sources. The lines span the
      region 230-590 nm. For the 14 most prominent lines the absolute irradiances
      should be useful for radiometric calibrations at an uncertainty level of ~15%
      195% confidence2. The ratios of the irradiances for this same group of lines are
      significantly more reproducible; they should be useful at an uncertainty level of
      ~10%.

PMID- 21068981
TI  - Solid-block stationary Fourier-transform spectrometer.
AB  - A solid-block stationary Fourier-transform spectrometer (SBSFTS) is described
      that is applicable to a wide range of portable, moderate-resolution
      instrumentation needs that include the detection of temporally variant
      signatures. The SBSFTS is a low-cost, extremely rugged stationary Fourier
      transform spectrometer based on the combination of three standard prism types.
      The SBSFTS uses a source-doubling, square-and-triangle common-path topology that
      is mechanically rugged, simple to align, and virtually immune to alignment
      perturbation. Its alignment stability makes it suitable for use in a variety of
      hostile operating environments. When coupled to a fiber-optic input, the
      spectrometer can be constructed in an extremely compact form. Experimental
      results have demonstrated the design and the performance of the spectrometer.

PMID- 21068982
TI  - Mixed films of TiO(2)-SiO(2) deposited by double electron-beam coevaporation.
AB  - <p>We used double electron-beam coevaporation to fabricate TiO(2)-SiO(2) mixed
      films. The deposition process included oxygen partial pressure, substrate
      temperature, and deposition rate, all of which were real-time computer
      controlled. The optical properties of the mixed films varied from pure SiO(2) to
      pure TiO(2) as the composition of the films varied accordingly. X-ray diffraction
      showed that the mixed films all have amorphous structure with a SiO(2) content of
      as low as 11%. Atomic force microscopy showed that the mixed film has a smoother
      surface than pure TiO(2) film because of its amorphous structure.</p><p>Linear
      and Bruggeman's effective medium approximation models fit the experimental data
      better than other models.</p>

PMID- 21068983
TI  - Packing-density calculation of thin fluoride films from infrared transmission
      spectra.
AB  - Optical thin films of MgF(2) and NdF(3) have been made by molecular-beam
      deposition in ultrahigh vacuum. The film packing density was calculated from the
      water amount that filled the cavities of the films in air. For that the
      transmission in the IR spectral region with a characteristic water absorption
      band at a wave number of 3400 cm(-1) was measured. The influence on the packing
      density of a modification of thin-film morphology by stratification of very thin
      sublayers of different crystallizing fluorides is tested.

PMID- 21068984
TI  - Antireflection coatings designed for two different infrared substrates.
AB  - It is shown that it is possible to design normal-incidence antireflection
      coatings that simultaneously reduce the reflectance of two different substrates.
      Although this is at the expense of some deterioration in performance when
      compared with that of conventional coatings, it can lead to significant time and
      cost savings in small thin-film production facilities. Numerical examples are
      presented for ZnS/ZnSe, Si/Ge, and ZnS/Ge substrate pairs. The experimental
      measurements on one such coating are in good agreement with the calculated
      performance.

PMID- 21068985
TI  - Characterization of symmetric, absorbing 50-50 beam splitters.
AB  - The equality of the transmitted and reflected irradiances by a symmetric,
      absorbing beam splitter consisting of three media is considered. The condition of
      minimum absorptance and the phase difference between the transmitted and
      reflected fields are studied as well.

PMID- 21068986
TI  - Incoherent transmissivity and reflectivity of an absorbing-plane plate or layer
      with linear variations in thickness.
AB  - The normal-incidence transmissivity and reflectivities (front and back) for the
      incoherent case are calculated for an absorbing-plane sample with linear
      variation of the thickness. Closed-form expressions for the direct determination
      of the energy (intensity) coefficients of a free-standing sample and of a film on
      a transparent substrate are given. The results are illustrated with the simulated
      infrared spectra of semiconductor InSb films of different thicknesses.

PMID- 21068987
TI  - Ambiguities in determining the optical constants for two reflection methods.
AB  - The Darcie-Whalen reflection method is ambiguous and has a chart area of 72%,
      which is less sensitive than method H-Owen's classification-which is unambiguous
      and has a chart area of 100%.

PMID- 21068989
TI  - Confocal theta fluorescence microscopy with annular apertures.
AB  - In a confocal theta fluorescence microscope, two objective lenses with circular
      apertures are used, one to illuminate the sample and the other to detect the
      emitted light at an angle to the illumination axis. We show that annular
      illumination and detection apertures lead to a reduction in the extent of the
      point-spread function. A spatial resolution improved by more than 50% can be
      achieved with a central obstruction blocking the inner 80% of the diameter. For
      the limit of a very narrow annular aperture and a numerical aperture of 0.75, the
      volume at half-maximum of the point-spread function is reduced from 15to5 aL.
      Amixed setup with anannular illumination aperture and a circular detection
      aperture is also considered.

PMID- 21068988
TI  - Theoretical analysis of confocal microscopy with microlenses.
AB  - Scanning confocal microscopy is well established and applied frequently in
      biomedical science and more recently in engineering disciplines. For technical
      applications a confocal principle based on microlens arrays was developed. The
      principle permits a high depth resolution on a large field. A theoretical
      analysis of this principle together with some experimental results are presented.

PMID- 21068990
TI  - Linnik microscope imaging of integrated circuit structures.
AB  - Experimental one-dimensional intensity and phase images of thick (>200 nm) oxide
      lines on silicon are presented together with profiles predicted from the
      waveguide model. Experimental results were obtained with a purpose-built Linnik
      interference microscope that makes use of phase-shifting interferometry for
      interferogram analysis. Profiles have been obtained for both TE and TM
      polarizations for a wide range of focal positions and in both bright-field [type
      1(a)] scanning and confocal modes of microscope operation. The results show
      extremely good agreement despite several simplifying assumptions incorporated
      into the theoretical model to reduce computing times.

PMID- 21068991
TI  - All-sky camera with a concave mirror.
AB  - The characteristics of an all-sky camera with a concave mirror are analyzed. A
      differential equation for a concave aspheric mirror with constant angular
      magnification is derived for the general dependence of the camera image height on
      the camera field angle. This equation is solved in parametric form for the case
      of a concave mirror with a constant angular magnification. The explicit equations
      for the shape of the aspheric mirror are given for some particular values of the
      angular magnification. Parametric equations of the surface shape for sevenfold
      angular magnification are developed into a power series that is used to analyze
      the imaging performance of such a mirror. The performance of the concave aspheric
      mirror is compared with that of a spherical mirror. The minimal camera-to-mirror
      distance is determined as a function of the blur allowed and the camera lens
      aperture. Some characteristics of convex mirrors are also presented for
      comparison.

PMID- 21068992
TI  - Fiber-optic Faraday-effect magnetic-field sensor based on flux concentrators.
AB  - The principles and performance of a fiber-optic Faraday-effect magnetic-field
      sensor designed around an yttrium-iron-garnet (YIG) sensing element and two flux
      concentrators are described. The system design exploits the technique of
      polarization-rotated reflection in which a single polarization-maintaining
      optical fiber links the sensor head to the optical source and detection system.
      In the sensing head, ferrite flux concentrators are magnetically coupled to the
      YIG sensing element to achieve maximum sensitivity. The system exhibits a noise
      equivalent field of 6 pT/?Hz and a 3-dB bandwidth of~10 MHz.

PMID- 21068993
TI  - High-accuracy calculations of the refractive indices of optical materials in a
      wide spectral range.
AB  - The interaction between light and matter is studied thoroughly by means of the
      quantum theory. On the basis of it, the refractive indices of types of optical
      materials are calculated by several formerly experienced formulas. Finally,anew,
      tested approximate formula with the highest calculated accuracy is obtained, and
      some groups of valuable parameters are given.

PMID- 21068994
TI  - Wigner distribution function applied to third-order aberrations.
AB  - The Wigner-distribution-function description of light beams is extended to
      aberrated optical systems. The simulations performed show that the different
      types of aberrations can be identified separately by the use of experimental
      devices that display projections of the Wigner distribution function of a two
      dimensional beam.

PMID- 21068995
TI  - Optical tomography by the temporally extrapolated absorbance method.
AB  - The concept of the temporally extrapolated absorbance method (TEAM) for optical
      tomography of turbid media has been verified by fundamental experiments and image
      reconstruction. The TEAM uses the time-resolved spectroscopic data of the
      reference and object to provide projection data that are processed by
      conventional backprojection. Optical tomography images of a phantom consisting of
      axisymmetric double cylinders were experimentally obtained with the TEAM and time
      gating and continuous-wave (CW) methods. The reconstructed TEAM images are
      compared with those obtained with the time-gating and CW methods and are found to
      have better spatial resolution.

PMID- 21068996
TI  - Chromaticity-discrimination thresholds with aperture and object colors:
      experimental results and predictions of some recent color-difference formulas.
AB  - Threshold-discrimination ellipses were obtained by three normal observers, at
      five color centers, by the use of two experimental devices, which provided light
      surface colors, and the same method and experimental conditions. The ellipses
      obtained for each center in both devices were quite similar when the sample
      distributions were appropriate and slightly smaller for object color than for
      aperture color. The ellipses predicted by three recent color-difference formulas
      based on the CIE uniform color space (CIELAB) were compared with those
      experimentally obtained by us as well as by other researchers who analyzed a
      greater number of color centers. The color-difference formula proposed by the CIE
      Technical Committee 1-29 [Color Res. Appl. 18, 137 (1993)] provides the best
      prediction of the semiaxis relationship for all the experimental datasets used,
      confirming their good performance in previous works [Appl. Opt. 33, 8069 (1993)],
      although the differences with respect to the experimental results are higher than
      those attributable to the interobserver variability.

PMID- 21068997
TI  - Shack Hartmann wave-front measurement with a large F-number plastic microlens
      array.
AB  - A new plastic microlens array, consisting of 900 lenslets, has been developed for
      the Shack Hartmann wave-front sensor.The individual lens is 300 um * 300um and
      has a focal length of 10 mm, which provides the same focal size, 60 um in
      diameter, with a constant peak intensity. One can improve thewave-front
      measurement accuracy by reducing the spot centroiding error by averaging a few
      frame memories of an image processor. A deformable mirror for testing the wave
      front sensor gives anappropriate defocus and astigmatism, and the laser wave
      front is measured with a Shack Hartmann wave-front sensor. The measurement
      accuracy and reproducibility of our wave-front sensor are better than lambda/20
      and lambda/50 (lambda = 632.8 nm),respectively, in rms.

PMID- 21068998
TI  - Spherical particle size determination by analytical inversion of the UV-visible
      NIR extinction spectrum.
AB  - An analytic inversion method, based on the anomalous diffraction approximation
      for nonabsorbing spherical particles, was developed to retrieve the size
      distribution from the optical turbidity or extinction spectrum. This method makes
      use of a differential Fourier cosine transform approach and provides a simple and
      fast inversion by means of fast Fourier transform and the Savitzky-Golay filter.
      The applicability of this algorithm was tested on the extinction data generated
      by the Mie solution. The effects of noise, modality, band limits, and data set
      size were analyzed by comparison with simulated data. This method can be used to
      reconstruct the original monomodal and bimodal distributions from 10% noise
      corrupted data. The peak position and ratio of peak heights can be recovered with
      10% or less deviation. The experiments with latex spheres showed that the
      inversion result from this method compares favorably with that from the dynamic
      light scattering measurement.

PMID- 21068999
TI  - Thickness determination of a water film on dye-doped ice by fluorescence
      spectroscopy.
AB  - A new method for measuring the thickness of a micrometer-thin water film on ice
      is presented. The method is based on confocal detection of fluorescence light,
      emitted by a special coumarin dye dissolved in ice as well as in water. The
      spectral position of the fluorescence maximum depends strongly on the matrix
      surrounding the dye molecules. Thus the analysis of the spectra obtained while
      the focal position perpendicular to the liquid-ice interface is scanned provides
      the possibility of measuring the thickness of the water film with the vertical
      resolution of the confocal system. We demonstrate this principle by a model
      system.

PMID- 21069000
TI  - Absolute, high-resolution optical position encoder.
AB  - Modern computer-controlled manufacturing machinery requires the absolute and
      highly accurate measurement of the linear position. Such an absolute, optical
      linear position encoder is described here. It is based on the transilluminance of
      a glass scale with an inexpensive light-emitting diode. The scale has two code
      tracks, one based on a pseudo-random binary sequence for the coarse determination
      of position and another periodic code for accurate fine-position measurement. A
      single-lens telecentric optical system images the code tracks in a mechanically
      insensitive way onto a custom photodetector. This special detector IC is capable
      of determining the components of the (complex) Fourier transform for the spatial
      frequency of the periodic code. The absolute optical position encoder shows a
      resolution of 10 nm and an absolute accuracy of better than 100 nm over short
      distances, verified with a commercial laser interferometer.

PMID- 21069001
TI  - Rapid, noninvasive concentration measurements of aqueous biological analytes by
      near-infrared Raman spectroscopy.
AB  - Accurate concentration measurements of glucose, lactic acid, and creatinine in
      saline solution have beena chieved with near-IR Raman spectroscopy and a partial
      least-squares analysis. The Raman spectra were acquired remotely through optical
      fibers. A root-mean-squared prediction error of 1.2 mM for glucose concentration
      was achieved in 100 s. Concentrations of other analytes were predicted with
      similar accuracy.

PMID- 21069002
TI  - Maximum rate of change of the differential reflection phase shift with respect to
      the angle of incidence for light reflection at the surface of an absorbing
      medium: Erratum.

PMID- 21069003
TI  - Exposure-induced high-pass filtering of a volume by means of an absorption
      hologram recording technique.
AB  - High-pass filtering effects have long been noted during recording of Fourier-type
      holograms on a saturable medium [Collier et al., Optical Holography (Academic,
      New York, 1971), p. 405]. The origin of the filtering effect lies in recording an
      absorption hologram such that the diffraction efficiency of strong spatial
      frequencies is significantly reduced by the saturable nature of the film. A
      simple optical configuration is used to take advantage of this effect in order to
      reduce the depth-of-focus noise associated with particle holography. The origin
      of the noise is clutter produced by a field of out-of-focus particles in which
      the particle under scrutiny exists [Reynolds et al., The New Physical Optics
      Notebook: Tutorials in Fourier Optics(Society of Photo-Optical Instrumentation
      Engineers, Belling-ham, Washington, 1989), p. 2054. A theoretical basis for the
      filtering is presented. Experimental results are shown.

PMID- 21069004
TI  - Fourier-transformation, phase-iteration, and least-square-fit image processing
      for Young's fringe pattern.
AB  - The fast Fourier transform, phase iteration, and the least-square fit are
      combined into an automated processing technique for the analysis of Young's
      fringe patterns. A Young's fringe pattern is first fast-Fourier-transform
      filtered to get an initial phase, phase iteration is carried out to improve the
      phase if necessary, and then the phase is least-square fitted to a phase plane.
      The magnitude and the direction of the displacement associated with the Young's
      pattern are determined from the phase plane.

PMID- 21069005
TI  - Disk-growing algorithm for phase-map unwrapping: application to speckle
      interferograms.
AB  - Interferometric techniques combined with phase shifting allow computation of the
      phase that is linked to the displacement of the object under study. The phases
      before and after displacement are computed from three or more interferograms
      (called specklegrams when speckle is used as the information carrier).
      Subtraction of these two phase patterns leads to a raw phase map. Phase
      unwrapping restores the 2pi discontinuities and gives a continuous phase map. The
      disk-growing algorithm presented allows the inner and the outer propagation of
      the unwrapping from a growing disk and so avoids the main problem of anisotropic
      error propagation for noisy phase maps. It works successfully in speckle
      interferometry.

PMID- 21069006
TI  - Compact all-optical bypass-exchange switch.
AB  - An electronically or optically addressed compact optical bypass-exchange switch
      is investigated and experimentally demonstrated.The switch is polarization based
      and consists of a controllable lambda/2 platesandwiched between two polarizing
      beam displacers. The input and the output signals propagate normal to the
      switching array, which makes the switch extremely attractive for cascading
      switching arrays, as found in multistage interconnect networks. A complete, all
      optical interconnection network is suggested.

PMID- 21069007
TI  - Coherence-multiplexed acousto-optic correlator for signal processing: theory and
      applications.
AB  - A method of multichannel processing to compute correlation products
      simultaneously is introduced. The signals that process are encoded on a single
      light beam through the use of an electro-optic modulators that induce optical
      delays greater than the coherence length of light. The coherence-modulated light
      beam thus obtained is then spatially and temporally modulated through an acousto
      optic Bragg cell. The potential number of channels is estimated to be
      approximately 5-10. The method can be combined with other existing systems, such
      as time-, space-, or frequency-multiplexed correlators, to increase the channel
      number. The method also applies to high-resolution spectral analysis.

PMID- 21069008
TI  - Sheared-beam imaging: an evaluation of its optical compensation of thick
      atmospheric turbulence.
AB  - Sheared-beam imaging (SBI) should compensate the effects of an idealized layer of
      turbulence located either in a transmitter/detector plane or in an object plane.
      This motivated the study of optical compensation of SBI in the presence of
      uniformly distributed turbulence over long horizontal paths in the cases of
      ideally smooth and ideally rough extended objects. The phase error along a one
      dimensional wave front resulting from SBI observation is computed numerically in
      the long-path regime and is compared with that of an equivalent conventional
      system for the case of a large smooth object. It is found that for the conditions
      considered the phase errors of the SBI system are greater than those of a
      conventional system. In the case of an ideally rough object the extra information
      furnished by the SBI observations does not lead to data that can be inverted to
      compute an image by the conventional shearing-interferometric algorithm. The
      phase errors in imaging a point reflector, however, are perfectly compensated.

PMID- 21069009
TI  - Direct image transmission through a multimode optical fiber.
AB  - One-way transmission of a multipixel image through the multimode optical fiber
      based on the phase-conjugation principle is realized. Adistortion-compensating
      hologram for each pixel of an image to be transmitted is superposed on a
      photoplate. Each hologram is recorded with a reference beam of different beam
      incidence angle to provide proper wave-front correction for each pixel without
      any interference from other pixels. The reference beams are holographically
      generated from a photoplate in which small holographic lenslets are aligned in a
      matrix pattern. Images of up to 25 pixels are transmitted through the fiber
      experimentally.

PMID- 21069010
TI  - Coherent transient optical signal processing without brief pulses.
AB  - The temporal processing operations of convolution and correlation are
      demonstrated through optical coherent transient techniques, in which two long,
      low-intensity frequency-chirped pulses replace the single, brief reference pulse
      of a traditional three-pulse excitation sequence (brief pulse, pattern pulse, and
      data pulse). Here, a four-pulse excitation sequence is used (two frequency
      chirped pulses, pattern pulse, and data pulse) in which the particular order and
      timing of the chirped pulses with respect to the other waveforms determine the
      processing operation. An experiment is performed with biphase-coded pattern and
      data pulses to demonstrate both the correlation and the convolution operations. A
      new atomic rephasing process that we call delayed rephasing is demonstrated.

PMID- 21069011
TI  - Modified fringe-adjusted joint transform correlation to accommodate noise in the
      input scene.
AB  - A modified fringe-adjusted joint transform correlator is proposed that is able to
      accommodate noise in the input scene. The effect of noise in the input scene on
      the performance of the joint transform correlator is analyzed and quantified.
      When the target is embeddedin aseverely noise-corrupted input scene, it is shown
      that the proposed modified fringe-adjusted filter joint transform correlator
      delivers a better correlation performance and the capacity to accommodate this
      noise than does the fringe-adjusted filter-based correlator. When the power
      spectra of the input image and the reference image are subtracted from the power
      spectrum of the joint-input image, it is found that the noise effect on the
      output plane is independent of the objects in the input scene and originates from
      the convolution of the reference image and noise in the input scene.

PMID- 21069012
TI  - Fractional correlation operation: performance analysis.
AB  - The fractional correlation is a new tool related to the fractional Fourier
      transform. It is useful for comparison and recognition, especially for shift
      variant cases. The performances of such a correlator are analyzed according to
      the standard criteria of signal-to-noise ratio, correlation sharpness (peak-to
      correlation energy), and Horner efficiency. The conclusions are that the
      performance is object dependent and that for nonwhite noise, compared with the
      conventional correlator, improved performances are possible. In addition we show
      that for a white-noise spectrum the fractional correlation has performances
      similar to the conventional correlator.

PMID- 21069013
TI  - Performance of a phase-transformed input joint transform correlator.
AB  - Conventionally a detected image is represented by an intensity array owing to the
      square-law nature of most detectors. However, this does not mean that we have to
      restrict ourselves to using intensity images for the correlation process.
      Transforming intensity images into phase images before correlation, which can be
      easily realized by a phase-modulation spatial light modulator, offers an
      alternative approach for high-performance pattern recognition. A phase
      transformed input joint transform correlator is investigated in detail in terms
      of pattern discriminability, detection efficiency, and noise robustness. We show
      that the phase-transformed joint transform correlator has higher pattern
      discriminability and detection efficiency than the conventional joint transform
      correlator, and it also offers a better trade-off between the pattern
      discriminability and noise tolerance. A proof-of-concept experiment is also
      provided.

PMID- 21069014
TI  - Composite training images for synthetic discriminant functions.
AB  - The use of composite images allows more images to be included in the construction
      of synthetic discriminant functions without increasing the training-set
      cardinality. This provides lower computational overhead or allows inclusion of
      more training information for the same computational load. The procedure is
      demonstrated with the minimum-average-correlation-energy synthetic discriminant
      function as an example.

PMID- 21069015
TI  - Distortion-invariant pattern recognition with Fourier-plane nonlinear filters.
AB  - The use of nonlinear techniques in the Fourier plane of pattern-recognition
      correlators can improve the correlators' performance in terms of discrimination
      against objects similar to the target object, correlation-peak sharpness, and
      correlation noise robustness. Additionally, filter designs have been proposed
      that provide the linear correlator with invariance properties with respect to
      input-signal distortions and rotations. We propose simple modifications to
      presently known distortion-invariant correlator filters that enable these filter
      designs to be used in a nonlinear correlator architecture. These Fourier-plane
      nonlinear filters can be implemented electronically, or they may be implemented
      optically with a nonlinear joint transform correlator. Extensive simulation
      results are presented that illustrate the performance enhancements that are
      gained by the unification of nonlinear techniques with these filter designs.

PMID- 21069016
TI  - Fourier-transform evaluation of phase data in spatially phase-biased TV
      holograms.
AB  - TV holograms for spatial phase stepping are formed with a small angular offset
      between the object and the reference beams to give a spatial frequency bias to
      the pattern recorded by the TV camera. It is common to set the bias so that there
      is a 90 degrees  or 120 degrees phase shift between adjacent pixels and to use
      the irradiance of three or more adjacent pixels to evaluate the phase of the
      interference. We report the Fourier-transform evaluation of such recordings to
      obtain their phase data. We also demonstrate the direct calculation of the phase
      difference between successive recordings without intermediate calculation of the
      random phase of each hologram. This technique is proposed as an approach to
      pulsed TV holography.

PMID- 21069017
TI  - Binary adaptive optics: atmospheric wave-front correction with a half-wave phase
      shifter: addenda.

PMID- 21069018
TI  - Particulate-matter distribution and its flow from power plants using infrared
      spectrometry and thermodynamics for in situ continuous emissions monitoring.
AB  - Spectroscopy measurements made through a continuum having suspended particulate
      matter are addressed. The applications presented permit correction of spectral
      transmissions as effected by particulate-producing fossil-fuel combustion. The
      research is especially applicable to large effluent flows from coal-fired power
      plants, whose effluents are studied with in situ (smokestack) radiometers.
      Methods involving fast calculation procedures based on measured irradiances in
      unabsorbed regions of the IR spectrum are presented. The methodology is based on
      wavelength-dependent extinction of radiation by small particles, considering both
      elastic scattering and absorbing effects. This extinction leads to an observed
      skeweness (or shift) of the blackbody spectral shape. Based on such skeweness,
      the particulate number distribution is determined with Mie theory. In order to
      simplify, and to speed up the routine for real-time application, a two-step
      procedure is presented. During preinstallation calibration with Mie theory, sets
      of integral tables are computed for all possible solution values and stored in
      computer memory. Based on instantaneous spectral measurements, the appropriate
      integral tables are retrieved, then used as inputs in a process leading to
      particulate number distribution. Because all time-consuming calculations
      associated with Mie theory are performed during preinstallation calibration, the
      technique is capable of monitoring particulate emission in real time.
      Furthermore, given resolution of the number distribution in combination with
      thermodynamic analysis of the system, determination of particulate apparent
      density and particulate mass flow rate is made. These values have importance for
      environmental reporting. Comparisons of calculated particulate distributions with
      in situ measurements are also presented. Confirmatory testing programs conducted
      at several power plants are discussed.

PMID- 21069019
TI  - Discretely tunable multiwavelength diode-pumped Nd:YALO laser.
AB  - Operation of a moderate-to-high repetition-rate Q-switched quadrupled diode
      pumped Nd:YALO laser discretely tunable between 266 and 275 nm is reported.
      Intracavity frequency doubling of the fundamental yielded 5.4 and 4.4 mJ at 532
      and 550 nm, respectively, at a 600-Hz repetition rate. The laser radiation was
      frequency quadrupled to the UV external to the cavity with an output of 0.28 and
      0.24 mJ at 266 and 275 nm, respectively. Astigmatic focal lengths that are due to
      thermal lensing effects of the Nd:YALO rod in the side-pumping geometry are
      presented.

PMID- 21069020
TI  - Diode laser mode selection using a long external cavity.
AB  - We describe a simple and practical scheme to control the operation of a diode
      laser in a specific longitudinal mode through the use of a long external cavity.
      We show that for a fixed laser current and temperature, the laser can selectively
      oscillate in several different modes by controlling the external-cavity length.
      With a simultaneous sweep of the laser current and the cavity length, the laser
      frequency can be continuously scanned by more than 10 GHz. This laser system has
      been used successfully in a laser cooling experiment of neutral atoms.

PMID- 21069021
TI  - Hollow-waveguide delivery systems for high-power, industrial CO(2) lasers.
AB  - Hollow-sapphire and metal-dielectric-coated hollow-glass waveguides have been
      used to deliver CO(2) laser power for industrial laser applications. The
      transmission, bending loss, and output-beam properties of these waveguides are
      described. The bore sizes of the hollow-sapphire waveguides were 1070 and 790
      MUm, and the hollow-glass waveguide had a bore of 700 MUm. The waveguides ranged
      in length from 1.1 to 1.5 m. The sapphire waveguides were bent to 90 degrees ,
      and the hollow-glass waveguides were bent into a full 360 degrees  loop. We
      delivered a maximum of 1.8 kW through the 1070-MUm-bore sapphire waveguide and
      1.0 kW through the hollow-glass waveguide. All the hollow waveguides incorporated
      a water jacket to prevent overheating.

PMID- 21069022
TI  - New interferometric fiber-optic gyroscope with amplified optical feedback.
AB  - A novel interferometric fiber-optic gyroscope with amplified optical feedback by
      an Er-doped fiber amplifier (EDFA) is proposed and theoretically investigated
      (the proposed gyroscope is named the feedback EDFA-FOG, FE-FOG in what follows).
      The FE-FOG functions like a resonant fiber-optic gyro (R-FOG) because of its
      multiple utilization of the Sagnac loop; however, it is completely different
      because a low-coherence light source is used. In addition, the gyro output signal
      is pulsed because the modulation frequency of the phase modulator placed in the
      Sagnac loop is selected to match the total round-trip time delay of the light,
      which includes the Sagnac-loop delay plus that of the feedback loop of the fiber
      amplifier. The sharpness of the output pulse can be adjusted by both the gain of
      an EDFA and the modulation depth of the phase modulator. When rotation occurs the
      peak position of the output pulse is shifted as a result of the Sagnac effect.
      The resolution of the rotation measurement depends on the sharpness of the output
      pulse. The techniques of both the open-loop and closed-loop methods are described
      in detail, which shows the great advantage of the proposed gyroscope over the to
      the conventional interferometric fiber-optical gyroscope (I-FOG).

PMID- 21069023
TI  - Theoretical study of coaxial fibers.
AB  - A mathematical solution of the wave equation for coaxial fibers having four
      different refractive-index profiles is presented. The transcendental equations
      are obtained under LP approximation and calculated for comparison of HE(mn)-mode
      dispersion characteristics. Attention is paid to the HE(11) and HE(12) modes
      because of their importance for modeling directional couplers, and calculations
      are carried out to obtain dispersion dependence on dimensional parameters of the
      fibers. The field expressions also are given, and the spatial distributions of
      the HE(11) and HE(12) modal fields of all coaxial structures for different
      conditions of propagation are calculated.

PMID- 21069024
TI  - Vacuum-tuned graded-index polymer waveguides on silicon substrates.
AB  - A new method for producing graded-index (GRIN) profiles on type A photolime gel
      based polymer waveguides with vacuum drying is demonstrated. Vacuum drying allows
      optical waveguides to be built on substrates with a higher index of refraction
      without intermediate lower-index cladding layers while keeping the concentration
      of various dopants unperturbed. The waveguide-loss and GRIN profiles were
      compared for vacuum-dried and alcohol-dried samples. Waveguide losses from 0.1 to
      10 dB/cm were observed.

PMID- 21069025
TI  - Diode-laser-to-waveguide butt coupling.
AB  - A diode-laser-to-waveguide butt-coupling model is described. The model takes into
      consideration the Fabry-Perot reflection and transmission of the etalon formed by
      the laser front facet and the waveguide entrance facet. The model predicts
      coupling efficiency and the coupled-power fluctuations that occur versus the
      separation between the laser and the waveguide. Calculations performed for Fabry
      Perot-laser-to-KTP waveguide coupling show that the transverse and the angular
      alignment tolerances of the waveguide can be increased when the waveguide
      entrance facet is antireflection coated. The longitudinal alignment tolerance of
      the waveguide can be increased by use of an index-matching gel between the laser
      and the waveguide.

PMID- 21069026
TI  - Comparison of Sagnac and Mach-Zehnder ultrafast all-optical interferometric
      switches based on a semiconductor resonant optical nonlinearity.
AB  - We present a theoretical analysis of recently demonstrated ultrafast all-optical
      interferometric switching devices (based on Sagnac and Mach-Zehnder
      interferometers) that use a large optical nonlinearity in a resonant regime.
      These devices achieve ~10-ps switching windows and do not require high-energy
      optical control pulses. We theoretically analyze and compare one Sagnac and two
      Mach-Zehnder switching configurations.

PMID- 21069027
TI  - Interpolation errors in UV-visible spectroscopy for stratospheric sensing:
      implications for sensitivity, spectral resolution, and spectral range.
AB  - UV-visible measurements of stratospheric constituents require the ratio of a pair
      of spectra to be determined. If their wavelength calibrations differ and if an
      array detector is used, at least one spectrum must be interpolated. This
      introduces error if the spectrum is undersampled; the error is smaller if
      wavelength stability is good. Increasing the sampling ratio by making the
      spectral resolution poorer reduces the optical depths of absorption by
      constituents. Exact values of interpolation errors from real spectra are a
      difficult topic, but with a theoretical study with a simulated spectrum we show
      that the sampling ratio should exceed ~4.5 pixels/FWHM but need not exceed 6.5
      pixels/FWHM. To avoid significant reduction in the optical depth of NO(2), the
      resolution should be smaller than ~1.0 nm FWHM. Hence a spectrometer system that
      measures both OClO and NO(3) by observing one order from one stationary grating
      should have more than ~1500 pixels, more than many currently available array
      detectors.

PMID- 21069028
TI  - Retrieval analysis of aerosol-size distribution with simulated extinction
      measurements at SAGE III wavelengths.
AB  - The retrieval of aerosol-size distribution from simulated aerosol-extinction
      coefficient measurements of the new satellite instrument, the Stratospheric
      Aerosol and Gas Experiment (SAGE) III, is investigated. A detailed discussion on
      the aerosol-size-distribution information content of the SAGE III aerosol
      extinction-coefficient measurement is provided. Results of the investigation
      indicate that unimodal as well as bimodal log-normal size distributions can be
      inferred. In addition, it is shown that a shape-constraint-free size distribution
      can be derived from SAGE III aerosol measurements by use of the randomized
      minimization search technique and the optimal estimation theory.

PMID- 21069029
TI  - Laser ranging and mapping with a photon-counting detector.
AB  - We propose a new technique for remote sensing: photon-counting laser mapping.
      MicroChannel plate detectors with a crossed delay-line (MCP/CDL) readout combine
      high position accuracy and subnanosecond photon timing, at event rates of 10(6)
      detected photons per second and more. A mapping system would combine an MCP/CDL
      detector with a fast-pulse, high-repetition-rate laser illuminator. The system
      would map solid targets with exceptional in-range and cross-range resolution. The
      resulting images would be intrinsically three dimensional, without resorting to
      multiple viewing angles, so that objects of identical albedo could be
      discriminated. For a detector time resolution and pulse width of the order of 10(
      10) s, the in-range resolution would be a few centimeters, permitting the
      discrimination of surfaces by their textures. Images could be taken at night, at
      illumination levels up to full moonlight, from ground, airborne, or space
      platforms. We discuss signal to noise as a function of laser flux and background
      level and present simulated images.

PMID- 21069030
TI  - Method to derive ocean absorption coefficients from remote-sensing reflectance.
AB  - A method to derive in-water absorption coefficients from total remote-sensing
      reflectance (ratio of the upwelling radiance to the downwelling irradiance above
      the surface) analytically is presented. For measurements made in the Gulf of
      Mexico and Monterey Bay, with concentrations of chlorophyll-a ranging from 0.07
      to 50 mg/m(3), comparisons are made for the total absorption coefficients derived
      with the suggested method and those derived with diffuse attenuation
      coefficients. For these coastal to open-ocean waters, including regions of
      upwelling and the Loop Current, the results are as follows: at 440 nm the
      difference between the two methods is 13.0% (r(2) = 0.96) for total absorption
      coefficients ranging from 0.02 to 2.0 m(-1); at 488 nm the difference is 14.5%
      (r(2) = 0.97); and at 550 nm the difference is 13.6% (r(2) = 0.96). The results
      indicate that the method presented works very well for retrieval of in-water
      absorption coefficients exclusively from remotely measured signals, and that this
      method has a wide range of potential applications in oceanic remote sensing.

PMID- 21069031
TI  - Estimating primary production at depth from remote sensing.
AB  - By use of a common primary-production model and identical photosynthetic
      parameters, four different methods were used to calculate quanta (Q) and primary
      production (P) at depth for a study of high-latitude North Atlantic waters. The
      differences among the four methods relate to the use of pigment information in
      the upper water column. Methods 1 and 2 use pigment biomass (B) as an input and a
      subtropical, empirical relation between K(d) (diffuse attenuation coefficient)
      and B to estimate Q at depth. Method 1 uses measured B, but Method 2 uses B
      derived from the Coastal Zone Color Scanner (subtropical algorithm) as inputs.
      Methods 3 and 4 use the phytoplankton absorption coefficient (a(ph)) instead of B
      as input, and Method B uses empirically derived a(ph)(440) and K(d) values, and
      Method 4 uses analytically derived a(ph)(440) and a (total absorption
      coefficient) values based on the same remote measurements as Method 2. When the
      calculated and the measured values of Q(z) and P(z) were compared, Method 4
      provided the closest results [for P(z), r(2) = 0.95 (n = 24), and for Q(z), r(2)
      = 0.92 (n = 11)]. Method 1 yielded the worst results [for P(z), r(2) = 0.56 and
      for Q(z), r(2) = 0.81]. These results indicate that one of the greatest
      uncertainties in the remote estimation of P can come from a potential mismatch of
      the pigment-specific absorption coefficient (a(ph)*), which is needed implicitly
      in current models or algorithms based on B. We point out that this potential
      mismatch can be avoided if we arrange the models or algorithms so that they are
      based on the pigment absorption coefficient (a(ph)). Thus, except for the
      accuracy of the photosynthetic parameters and the above-surface light intensity,
      the accuracy of the remote estimation of P depends on how accurately a(ph) can be
      estimated, but not how accurately B can be estimated. Also, methods to derive
      a(ph) empirically and analytically from remotely sensed data are introduced.
      Curiously, combined application of subtropical algorithms for both B and K(d) to
      subarctic waters apparently compensates to some extent for effects that are due
      to their similar and implicit pigment-specific absorption coefficients for the
      calculation of Q(z).

PMID- 21069032
TI  - Detection and imaging of nitrogen dioxide with the degenerate four-wave-mixing
      and laser-induced-fluorescence techniques.
AB  - The spectroscopic techniques of degenerate four-wave mixing (DFWM) and laser
      induced fluorescence (LIP) have been applied to the detection of minor species
      for combustion diagnostics. We compare the results obtained when these techniques
      are used to detect NO(2). Previous results show that DFWM signals increase for
      NO(2) when buffer gas is added and that LIP signals are greatly reduced under the
      same circumstances. We make direct quantitative comparisons of these two
      techniques and discuss their suitability for making measurements of NO(2) in
      combustion environments.

PMID- 21069033
TI  - Tunable KrCI excimer-laser operation for combustion diagnostics.
AB  - Operating conditions for a tunable XeCl excimer laser have been optimized for
      tunable narrow-band operation at 222 nm with KrCl, formed in Kr/He/Ne/HCl gas
      mixtures. This wavelength is interesting for detection of nitric oxide (NO) in
      combustion environments. The laser emission coincides with the (1, 1) and (2, 2)
      bands of the NO A-X system. Laser-induced-fluorescence spectra taken in a flame
      show specific excitation of NO with this laser.

PMID- 21069034
TI  - Temperature imaging in a supersonic free jet of combustion gases with two-line OH
      fluorescence.
AB  - Temperature measurements were performed in a shock-tunnel-generated free jet of
      hydrogen/oxygen reaction products diluted in argon with a nonsimultaneous, two
      excitation-line planar laser-induced fluorescence technique with the hydroxyl
      radical (OH) as a tracer. Single-shot images were obtained with broadband
      excitation of isolated transitions in the A(2)Sigma(+) ? X(2)Pi(1, 0) band of OH
      near 282 nm, with broadband, temporally integrated detection of the resulting
      nonresonant emission. A measurement of the fluorescence lifetime in the free jet
      showed no variation with excited rotational level, allowing the rotational
      temperature to be obtained from the ratio of single-shot images with laser
      excitation of different rovibronic transitions.

PMID- 21069035
TI  - Ray scattering by an arbitrarily oriented spheroid. I. Diffraction and specular
      reflection.
AB  - Diffraction and reflection of an arbitrarily polarized plane wave by an
      arbitrarily oriented spheroid in the short-wavelength limit are considered in the
      context of ray theory. A closed-form solution for both diffraction and reflection
      is obtained, and the polarization character of the diffracted plus reflected
      electric field is obtained. It is found that the magnitude of the reflected
      electric field is multivalued for forward scattering. This is interpreted in
      terms of the variation of the spheroid's Gaussian curvature at the points where
      grazing ray incidence occurs.

PMID- 21069036
TI  - Ray scattering by an arbitrarily oriented spheroid. II. Transmission and cross
      polarization effects.
AB  - Transmission of an arbitrarily polarized plane wave by an arbitrarily oriented
      spheroid in the short-wavelength limit is considered in the context of ray
      theory. The transmitted electric field is added to the diffracted plus reflected
      ray-theory electric field that was previously derived to obtain an approximation
      to the far-zone scattered intensity in the forward hemisphere. Two different
      types of cross-polarization effects are found. These are (a) a rotation of the
      polarization state of the transmitted rays from when they are referenced with
      respect to their entrance into the spheroid to when they are referenced with
      respect to their exit from it and (b) a rotation of the polarization state of the
      transmitted rays when they are referenced with respect to the polarization state
      of the diffracted plus reflected rays.

PMID- 21069037
TI  - Electromagnetic-field calculations for irregularly shaped, axisymmetric layered
      particles with focused illumination.
AB  - Theoretical procedures are presented for the determination of the internal and
      the near-surface electromagnetic fields for an arbitrary monochromatic field
      (e.g., a focused laser beam) incident upon an irregulary shaped, axisymmetric
      layered particle. The layered spherical particle solution is also given as a
      special case of the general solution. Systematic calculations are presented that
      demonstrate the effects of particle shape and incident focused-beam orientation
      on the electromagnetic-field distributions.

PMID- 21069038
TI  - Development of an algorithm for the calculation of the scattering properties of
      agglomerates.
AB  - A new, improved, and more efficient algorithm for calculation of the scattering,
      extinction, and absorption characteristics of agglomerates consisting of Rayleigh
      size primary particles is presented. The computer code is based on a new
      formulation of the light scattering for such agglomerates and is more than 10
      times faster than the codes based on previous formulations. The computational
      times required by the old and the new algorithms, run on VAX 7000, IBM 3090, and
      UNIX RS6000 mainframe computers, are compared for different agglomerate
      configurations, such as straight chains, clusters, and randomly branched chains.
      A distributed-parallel-computing scheme was used to run the new algorithm on four
      UNIX RS6000 processors concurrently, resulting in computational times 47 times
      faster than required for the calculations. Furthermore, the robustness and
      convenience of the algorithm are assessed.

PMID- 21069039
TI  - Patents.
AB  - 5,153,926; 5,387,997; 5,398,130; 5,404,414; 5,410,434; 5,410,563; 5,418,797;
      5,422,719; 5,436,459; 5,438,406; 5,438,455; 5,438,632; 5,440,422; 5,440,428.

PMID- 21069040
TI  - Modal analysis of noise in signal-processing-in-the-element detectors.
AB  - Detector noise limits the performance of signal-processing-in-the-element
      detectors. For detectors to be optimized, an expression for the signal and noise
      must be found. The results of the eigenmode solution to the charge transport
      problem are used to derive the power spectral density of the noise in analytic
      form. This result is then coordinated with a similarly obtained modulation
      transfer function to yield a frequency-dependent signal-to-noise ratio (SNR). The
      SNR is used to reveal performance trends over several ranges of detector
      parameters. The most important result is that the contact boundary velocity
      strongly controls the SNR. The optimum SNR condition occurs when the contacts are
      not perfectly ohmic but exhibit a partially blocking behavior.

PMID- 21069041
TI  - Basic theory of a four-lens optical system design.
AB  - The theory and the method of calculation of an optical system based on aberration
      parameters C, W, P are presented. These parameters define all the aberrations of
      optical systems. The method is based on the synthesis of multilens systems from
      the single elements. The formulas for the relationships of increments between the
      angles of the first paraxial ray and the increments in the basic parameters are
      introduced. These formulas permit the parameters to vary and correct the
      aberrations. These angle calculations of the first paraxial ray of a four-lens
      cemented and uncemented system are presented. It is a method for designing
      complex optical systems from the initial stage to the final stage with corrected
      aberrations.

PMID- 21069042
TI  - Analysis and observation of finite beam Bragg diffraction by a thick planar phase
      grating.
AB  - A numerical-impulse-response technique for studying the propagation and
      diffraction of finite-width beams in planar phase gratings is described. It can
      account for both symmetric and asymmetric diffractions. The grating-length-to
      beam-width ratio is shown to govern the extent of beam-profile distortion and
      selectivity sidelobe suppression. Trade-offs between diffraction efficiency and
      beam profile have also been demonstrated. Theoretical results have been verified
      by experimental observations in a planar waveguide geometry of diffracted beams
      that change from a single diffraction peak to multiple peaks as the grating
      length-to-beam-width ratio increases.

PMID- 21069044
TI  - Nondiffracting interference patterns generated with programmable spatial light
      modulators.
AB  - Nondiffracting beams are of interest for optical metrology applications because
      the size and shape of the beams do not change as the beams propagate. We have
      created a generating pattern consisting of a linear combination of two
      nondiffracting patterns. This pattern forms a nondiffracting interference pattern
      that appears as a circular array of nondiffracting spots. More complicated
      multiplexed arrays are also constructed that simultaneously yield two different
      nondiffracting patterns. We generate these Bessel function arrays with a
      programmable spatial light modulator. Such arrays would be useful for angular
      alignment and for optical interconnection applications.

PMID- 21069043
TI  - Intensity and phase measurements of nondiffracting beams generated with a magneto
      optic spatial light modulator.
AB  - Nondiffracting beams are of interest for optical metrology applications because
      the size of the beam does not change as the beam propagates. However, accuracy
      can be increased if the diameter of the beam is smaller. One technique for
      accomplishing this is to use the dark axial intensity profile associated with a
      higher-order nondiffracting Bessel function beam. We generate these higher-order
      Bessel function beams with a programmable spatial light modulator. We study the
      intensity patterns and the phase dependence of these nondiffracting beams. In
      addition, we examine interference effects caused by recording these patterns onto
      a binary spatial light modulator.

PMID- 21069045
TI  - Holographic correction of large telescope primaries by proximal, off-axis
      beacons.
AB  - Compact telescope configurations incorporating a holographic correction of large,
      low-quality primary collectors are demonstrated. Aberration correction is
      demonstrated with an off-axis laser beacon located close to the primary. This
      arrangement results in a compact telescope with minimum obscuration. The
      reduction of additional off-axis aberrations introduced by the method is also
      demonstrated.

PMID- 21069046
TI  - Frequency stability of high-finesse interferometers.
AB  - The effects of temperature and pressure on the stability of a high-finesse
      interferometer are considered, and the design of a high-finesse interferometer
      that minimizes these effects is presented. The high-finesse interferometer has a
      free spectral range of 23,600 MHz, a finesse of greater than 30,000, and a
      measured stability of better than 7 MHz/h (0.3 mfringes/h).

PMID- 21069047
TI  - Dispersion compensation in stellar interferometry.
AB  - In long-baseline stellar interferometry, spectrometers are used to disperse
      starlight for measuring visibility at multiple wavelengths and for fringe
      tracking with channeled spectra. However, neither prisms nor gratings are well
      suited to the observation of fringes with wide spectral bandwidths because the
      mapping from wave number to detector coordinate is nonlinear. The visibility
      measurement and fringe-tracking performance are affected by nonlinearity and in
      many cases it is important to compensate for this. Longitudinal-dispersion
      correctors may be used to compensate for differential air paths in an
      interferometer, and we show that these may also be used to correct the nonlinear
      mapping of a spectrometer.

PMID- 21069048
TI  - Application of geometric phase techniques to stellar interferometry.
AB  - In stellar interferometry the fringe visibility can be measured by modulating the
      optical path difference between the two arms of an interferometer. This approach
      yields accurate estimates of the fringe visibility only if the bandwidth is
      small, and this limits the sensitivity of the technique. We propose using a
      geometric phase modulator that is achromatic and does not suffer from bandwidth
      restrictions. Fringe detectors using geometric phase modulation have the
      potential of greatly increasing the sensitivity of optical stellar
      interferometers.

PMID- 21069049
TI  - Four-plate birefringent filter for high-gain pulsed dye laser tuning.
AB  - A complete quantitative analysis of a multistage birefringent filter has been
      used to design a four-plate filter for a high-gain dye laser. It is shown that
      both S and P polarization modes must be considered at all stages. The four-plate
      design, with thickness ratios of 1:2:4:8, succeeds where typical commercial
      designs (1:2:15 and 1:4:16) fail when used in a high-gain cavity. Calculations
      have been verified by performance measurements for a quartz filter. Design
      specifications are presented.

PMID- 21069050
TI  - Blackbody calibration sources of high accuracy for a spaceborne infrared
      instrument: the Along Track Scanning Radiometer.
AB  - We describe the two 140-mm-aperture simulated blackbody sources used for the on
      board calibration of the Along Track Scanning Radiometer, a spaceborne thermal
      infrared instrument for the accurate remote sensing of sea surface temperature,
      in operation since 1991. The design of these spaceborne sources, which operate at
      ~ -10  degrees C and ~ +30  degrees C, allows them to meet their unprecedented
      accuracy goal, namely a 3sigma uncertainty in their brightness temperature of
      <0.1 K for the whole mission. This performance is empirically demonstrated in the
      laboratory and in flight by long-term temperature readout tests, temperature
      uniformity measurements, and direct emissivity measurements.

PMID- 21069051
TI  - Laser action in polymeric gain media containing scattering particles.
AB  - Optical pumping of polymer sheets containing laser dyes and TiO(2) nanoparticle
      scatterers results in emissions that exhibit laser behavior with linewidths as
      low as 4 nm. The input-output characteristics, effects of index matching on the
      emission, damage thresholds, wavelength stability, and possible applications of
      these new materials are discussed.

PMID- 21069052
TI  - Optimal single-band normal-incidence antireflection coatings.
AB  - Mathematical and computational evidence that strongly suggests that optimal
      solutions exist to single-band, normal-incidence antireflection coating problems
      is presented. It is shown that efficient synthesis and refinement techniques can
      quickly and accurately find such solutions. Several visible and infrared
      antireflection coating examples are presented to support this claim. Graphs that
      show the expected optimal performance for different representative substrates,
      refractive-index ratios, wavelength ranges, and overall optical thickness
      combinations are given. Typical designs exhibit a pronounced semiperiodic
      clustering of layers, which has also been observed in the past. Explanations of
      this phenomenon are proposed.

PMID- 21069053
TI  - Original method for measurement of optical mode fields.
AB  - We report on a new method for measurement of mode spot sizes of fibers or
      waveguides (Ti-diffused or proton-exchanged waveguides on LiNbO(3)) that uses
      neither camera nor optics and works at any wavelength with a 1-MUm resolution.
      The measurements are in good agreement with a finite element simulation.

PMID- 21069054
TI  - Extrinsic optical-fiber ultrasound sensor using a thin polymer film as a low
      finesse Fabry-Perot interferometer.
AB  - Theoretical and experimental aspects of an extrinsic optical-fiber ultrasound
      sensor are described. The sensor is based on a thin transparent polymer film
      acting as a low-finesse Fabry-Perot cavity that is mounted at the end of a
      multimode optical fiber. Performance was found to be comparable with that of a
      piezoelectric polyvinylidene dinuoride-membrane (PVDP) hydrophone with a
      sensitivity of 61 mV/MPa, an acoustic noise floor of 2.3 KPa over a 25-MHz
      bandwidth, and a frequency response to 25 MHz. The wideband-sensitive response
      and design flexibility of the concept suggests that it may find application as an
      alternative to piezoelectric devices for the detection and measurement of
      ultrasound.

PMID- 21069055
TI  - Performance of a compact, hybrid optical evanescent-wave sensor for chemical and
      biological applications.
AB  - We describe a hybrid evanescent-wave sensor component that we fabricated by using
      an integrated optical interferometer with a specially adapted photodetector
      array. The design of the interferometer is based on the use of tapered waveguides
      to obtain two intersecting collimated beams. Phase shifts can be measured with an
      angular precision of better than 10(-3) rad, which corresponds to a superstrate
      index change inferior of 10(-6) with our structure. The interest in the device as
      a chemical sensor is experimentally demonstrated. The same optical component
      could be used in a variety of other sensor applications, e.g., biological and
      immunological sensors.

PMID- 21069056
TI  - Holographic particle-image velocimetry in the first International Microgravity
      Laboratory aboard the Space Shuttle Discovery.
AB  - In January 1992 the Space Shuttle Discovery carried the first International
      Microgravity Laboratory into Earth orbit for eight days. One of the many
      experiments carried out during the orbit was a combined study of triglycine
      sulfate crystal growth from solution and fluid-particle-dynamics studies in
      microgravity. Optical diagnostics included holocameras to provide concentration
      measurements and three-dimensional particle tracking. More than 1000 holograms
      that were recorded in space have been analyzed since the flight, providing a wide
      range of interesting conclusions about microgravity, crystal growth, and particle
      dynamics. This paper focuses on the results of holographic particle-image
      velocimetry experiments and provides an excellent example, along with new
      techniques, for exploiting holography for particle and flow diagnostics.

PMID- 21069057
TI  - Effect of lens distortion in optical step-and-scan lithography.
AB  - A model is presented with which the effect of lens distortion on the optical
      transfer function is calculated for a step-and-scan lithographic system. The
      spatially varying lateral image shift and the relative loss in modulation depth
      are derived from the exposure pattern that is built up during the image scanning.
      Other important phenomena such as lens aberrations, the effect of finite image
      aperture, and polarization are deliberately left out of the model; from the
      simplified model, analytic expressions can be obtained that relate the distortion
      coefficients of the projection system to the local shift and the relative loss in
      modulation depth of the exposed pattern that is built up during scanning. As a
      scanning aperture, we have taken either part of an annulus or a rectangular
      section in the image field.

PMID- 21069058
TI  - Surface morphologies of sputter-deposited aluminum films studied using a high
      resolution phase-measuring laser interferometric microscope.
AB  - Sputter-deposited aluminum (Al) film surface morphologies were studied with a new
      nondestructive method that incorporates a high-resolution phase-measuring laser
      interferometric microscope. Good correlation is obtained between rms roughness
      and reflectivity for various conditions of temperature and argon gas pressure. It
      should be noted that the rms roughness is much more sensitive than reflectivity
      when reflectivity exceeds 90%. A drastic change is observed in the temperature
      dependence of the rms roughness and the skewness at 200  degrees C. As a result
      there are changes in Al grain sizes and surface morphologies based on concomitant
      scanning electron microscope observations. We found that the rms roughness value
      depends on the resolution of the objective especially when the Al grain sizes are
      comparable to the resolution.

PMID- 21069059
TI  - Design and test of a simple high-temperature laser microrefractometer.
AB  - The design of a laser microrefractometer that is suitable for temperature
      dependent measurements is described. The refractive index of methylene iodide is
      measured in the temperature range of 22-92  degrees C for laser wavelengths
      covering almost the entire visible range of the spectrum: 442, 488, 515, 543,
      594, and 633 nm. A detailed analysis of the temperature-related experimental
      error is made.

PMID- 21069060
TI  - Fiber-coupler-based measurement of lenslet focal lengths.
AB  - In a technique reminiscent of the classic autocollimation method, we demonstrate
      that focal lengths of micro-optic lenses may be measured precisely by the use of
      a mirror and a 2 * 1 fiber coupler.

PMID- 21069061
TI  - Fiber-optic backreflectance method for determining the effective focal lengths of
      optical elements.
AB  - An alternative and simple fiber-optic backreflectance method for indirectly
      determining the effective focal lengths of optical elements by the spatial
      location of three specific points (the focal point and two object points) is
      presented. The basic optical element of the method is the single-mode optical
      fiber. It serves simultaneously as a point light source, an object for
      projecting, and a point receiver that is highly sensitive to spatial
      displacements for focused backreflectance laser emission. The method provides
      high accuracy for both locating the spatial points (1 um) and determining the
      effective focal length (less than 0.5%).

PMID- 21069062
TI  - Time-resolved photon emission from layered turbid media.
AB  - We present numerical and experimental results of time-resolved emission profiles
      from various layered turbid media. Numerical solutions determined by time
      resolved Monte Carlo simulations are compared with measurements on layered-tissue
      phantoms made from gelatin. In particular, we show that in certain cases the
      effects of the upper layers can be eliminated. As a practical example, these
      results are used to analyze in vivo measurements on the human head. This
      demonstrates the influence of skin, skull, and meninges on the determination of
      the blood oxygenation in the brain.

PMID- 21069063
TI  - Elastic light-scattering measurements of single biological cells in an optical
      trap.
AB  - We have developed an instrument for determination of the angular light scattering
      of beads and biological cells. The instrument uses radiation pressure for
      levitation of particles inside a cuvette. The setup consists of two 780-nm diode
      lasers in a vertical double-beam trapping configuration. In the horizontal
      direction a weakly focused 633-nm probe beam is used to illuminate the trapped
      particle. One can detect scattered light over the range of from - 150 to 150 deg
      with an angular resolution of 0.9 deg using an avalanche photodiode. With this
      setup light scattering from polystyrene beads was measured, and the obtained
      scattering patterns were compared with theoretical scattering patterns from
      Lorenz-Mie theory. The results show that the setup is stable, gives reproducible
      patterns, and qualitatively agrees with the calculations. Trapping of biological
      cells is more difficult than trapping of beads, because smaller forces result
      from smaller refractive indices. We present an angular scattering pattern
      measured from a human lymphocyte measured from 20 to 60 deg.

PMID- 21069064
TI  - Sensitivity studies for imaging a spherical object embedded in a spherically
      symmetric, two-layer turbid medium with photon-density waves.
AB  - We present analytic expressions for the amplitude and phase of photon-density
      waves in strongly scattering, spherically symmetric, two-layer media containing a
      spherical object. This layered structure is a crude model of multilayered tissues
      whose absorption and scattering coefficients lie within a range reported in the
      literature for most tissue types. The embedded object simulates a pathology, such
      as a tumor. The normal-mode-series method is employed to solve the inhomogeneous
      Helmholtz equation in spherical coordinates, with suitable boundary conditions.
      By comparing the total field at points in the outer layer at a fixed distance
      from the origin when the object is present and when it is absent, we evaluate the
      potential sensitivity of an optical imaging system to inhomogeneities in
      absorption and scattering. For four types of background media with different
      absorption and scattering properties, we determine the modulation frequency that
      achieves an optimal compromise between signal-detection reliability and
      sensitivity to the presence of an object, the minimum detectable object radius,
      and the smallest detectable change in the absorption and scattering coefficients
      for a fixed object size. Our results indicate that (l) enhanced sensitivity to
      the object is achieved when the outer layer is more absorbing or scattering than
      the inner layer; (2) sensitivity to the object increases with the modulation
      frequency, except when the outer layer is the more absorbing; (3) amplitude
      measurements are proportionally more sensitive to a change in absorption, phase
      measurements are proportionally more sensitive to a change in scattering, and
      phase measurements exhibit a much greater capacity for distinguishing an
      absorption perturbation from a scattering perturbation.

PMID- 21069065
TI  - Method of calculating the image resolution of a near-infrared time-of-flight
      tissue-imaging system.
AB  - A new method for calculating the image resolution for a near-infrared time-of
      flight tissue-imaging system is presented. The image resolution is calculated
      from the full width at half-maximum of the photon-path function along the
      midplane of the medium, integrated over all times of flight, and weighted by the
      time-resolved detector response. Detailed treatment of the optical gating
      mechanism shows that for some types of gating mechanism, there exists an optimal
      gating time beyond which the image resolution is not improved by arbitrarily
      decreasing the gating time. This theory predicts a limiting image resolution
      of~20% of the medium thickness, which is consistent with the research of others.

PMID- 21069066
TI  - Compound parabolic concentrator probe for efficient light collection in
      spectroscopy of biological tissue.
AB  - We describe a compound parabolic concentrator (CPC)-based probe for enhanced
      signal collection in the spectroscopy of biological tissues. Theoretical
      considerations governing signal enhancement compared with conventional collection
      methods are given. A ray-tracing program was used to analyze the throughput of
      CPC's with shape deviations and surface imperfections. A modified CPC shape with
      99% throughput was discovered. A 4.4-mm-long CPC was manufactured and
      incorporated into an optical fiber-based near-infrared Raman spectrometer system.
      For human tissue samples, light collection was enhanced by a factor of 7 compared
      with collection with 0.29-NA optical fibers.

PMID- 21069067
TI  - Lensless imaging by spatial Fourier synthesis holography.
AB  - The technique of Fourier synthesis holography is extended to the spatial domain.
      A spatially extended source is decomposed into its Fourier components, and a
      hologram of an object distribution is formed at each spatial frequency and stored
      in a computer. Upon synthesis in the computer a clear image can be formed of the
      object without the use of lenses.

PMID- 21069068
TI  - Diffuse-object holograms in silver halide emulsions: influence of the beam ratio
      on the efficiency and the signal-to-noise ratio.
AB  - The influence of the beam ratio between reference and object beam intensities on
      the characteristics of diffuse-object holograms recorded as volume phase
      holograms in bleached silver halide emulsion is experimentally analyzed.
      Measurements of the diffraction efficiency and the signal-to-noise ratio of the
      holograms are taken. The experimental results presented show that when the beam
      ratio increases, the diffraction efficiency decreases and the signal-to-noise
      ratio increases; these two holographic parameters behave in this way no matter
      what type of processing is used.

PMID- 21069069
TI  - Dynamic holographic interferometry by photorefractive crystals for quantitative
      deformation measurements.
AB  - A holographic interferometer that uses two-wave mixing in a photorefractive
      (Bi12SiO20) crystal under an applied ac field is described. The interferometer
      uses a repetitive sequence of separate record and readout times to obtain quasi
      real-time holographic interferograms of vibrating objects. It is shown that a
      good signal-to-noise ratio of the interferometer is obtained by turning off the
      object illumination and the applied ac field during readout of the hologram. The
      good signal-to-noise ratio of the resulting holographic interferograms enables
      phase measurement, which allows for quantitative deformation analysis.

PMID- 21069070
TI  - Hybrid two-dimensional subwavelength surface-relief grating-mesh structures.
AB  - The homogeneous behavior of periodic two-dimensional subwavelength surface-relief
      structures that contain both gratings and meshes (inverse gratings) are
      investigated. It is shown that when effective indices are synthesized near the
      higher index (substrate region), mesh structures yield larger feature sizes
      compared with their grating counterparts, whereas grating structures yield larger
      feature sizes when effective indices are synthesized near the lower index
      (incident region). For each type of structure investigated, a relation between
      the parameters of the structure and an effective refractive index is determined.
      It is shown that an equal area occupied by the high- or low-index media within
      the grating cell does not, in general, result in equal effective indices. The
      effective index of the grating is shown to be characterized by both the shape
      (local distribution) and the area of the high- or low-index medium within the
      unit grating cell. Finally, the advantages of subwavelength gratings and meshes
      are combined to produce hybrid grating-mesh structures that are less demanding on
      the fabrication process.

PMID- 21069071
TI  - Small-feature-size fan-out kinoform etched in GaAs.
AB  - A binary fan-out kinoform for focusing and splitting an incident beam into a 4 *
      4 spot array, with a largest deflection angle of 28 degrees , was designed,
      fabricated in GaAs, and evaluated. The kinoform was defined in resist with
      electron-beam lithography and etched into GaAs with chemically assisted ion-beam
      etching. Light at wavelength 0.98 um from a single-mode fiber was used to
      illuminate the kinoform. The efficiency was measured to be 34%, and the
      uniformity error for the 4*4 spots was 29%. Although the typical feature size of
      the kinoform is only roughly two wavelengths, we found that the scalar theory of
      diffraction can be used. A first kinoform was designed with the customary Fresnel
      diffraction theory, which was found to be too coarse, resulting in a fan-out
      exhibiting some distortion. A second kinoform was designed with the more rigorous
      Fresnel-Kirchhoff expression, and its fan-out shows no distortion.

PMID- 21069072
TI  - V-groove gratings on silicon for infrared beam splitting: comment.
AB  - In a recent paper [Appl. Opt. 34, 2556 (1995)] beam-splitter gratings with one or
      more v-shaped features within the period were designed by the complex-amplitude
      transmittance method. We argue that this approach leads to incorrect results in
      the geometries considered and provide the evidence of its failure by numerical
      calculations based on rigorous electromagnetic diffraction theory.

PMID- 21069073
TI  - V-groove gratings for infrared beam splitting: reply.
AB  - It is acknowledged that scalar diffraction theory may not be used to design
      accurately gratings with submicrometer features. This does not negate the concept
      of the v-groove beam-splitting grating.

PMID- 21069074
TI  - Unwrapping of interferometric phase-fringe maps by the discrete cosine transform.
AB  - Current whole-field interferometric techniques yield a phase distribution in
      modulo 2pi. Removal of the resulting cyclic discontinuities is a process known as
      unwrapping, which must be performed before the data can be interpreted. We
      investigate an iterative unwrapping technique recently published by Ghiglia and
      Romero [J. Opt. Soc. Am. A 11, 107 (1994)], which is based on least-squares
      minimization, obtained by the discrete cosine transform. We apply this technique
      to remove phase wraps from electronic speckle pattern interferometry data, using
      modest personal computer hardware. The algorithm is shown to be fast, easy to
      implement, robust in the presence of noise, and able to handle phase
      inconsistencies without propagating local errors.

PMID- 21069075
TI  - Contrast enhancement of underwater images with coherent optical image processors.
AB  - The use of coherent optical processors for improving the quality of degraded
      underwater images is discussed, and a holographic filter suitable for the
      enhancement of contrast in underwater images is described. The filter is a
      modified matched spatial filter, and it performs a nonlinear local contrast
      enhancement. The theory of the operation of the coherent optical image processor
      with this new filter is presented and experimentally verified. The removal of the
      backscattered light from underwater images is demonstrated under laboratory
      conditions. The results show an improvement in the overall image contrast.

PMID- 21069076
TI  - Recognition of damage in polarizing transmission-grating facets.
AB  - An optical setup was built for microscopic damage inspection on transmission
      grating facets composed of a gold-wire structure. Contrast improvement was
      achieved by exploiting the polarizing properties of these gratings in the near
      infrared region. Spatial filtering yields an additional contrast enhancement and
      reduces unwanted signals caused by the periodic support structure. An image
      processing algorithm is developed that evaluates the number and the size of the
      faults in a grating facet with high accuracy from only one digital image.

PMID- 21069077
TI  - Modeling the noise figure of an acousto-optic receiver.
AB  - By defining the processing gain of an acousto-optic receiver as the ratio of the
      signal-to-noise ratio at the output of the detector to the signal-to-noise ratio
      of the intermediate-frequency input, one can model a noise figure for the acousto
      optic receiver. The noise figure has a minimum of 0 dB and depends on the ratio
      of the noise power (internal to the acousto-optic cell) to the intermediate
      frequency input noise power multiplied by the frequency and the spatially
      dependent exponential factor.

PMID- 21069078
TI  - Coherent optical neural networks that have optical-frequency-controlled behavior
      and generalization ability in the frequency domain.
AB  - Coherent optical neural networks that have optical-frequency-controlled behavior
      are proposed as sophisticated optical neural systems. The coherent optical neural
      network system consists of an optical complex-valued neural network, a phase
      reference path, and coherent detectors for selfhomodyne detection. The learning
      process is realized by adjusting the delay time and the transparency of neural
      connections in the optical neural network with the optical frequency as a
      learning parameter. Generalization ability in frequency space is also analyzed.
      Information geometry in the learning process is discussed for obtaining a
      parameter range in which a reasonable generalization is realized in frequency
      space. It is found that there are error-function minima periodically both in the
      delay-time domain and the input-signal-frequency domain. Because of this reason,
      the initial connection delay should be within a certain range for a meaningful
      generalization. Simulation experiments demonstrate that a stable learning and a
      reasonable generalization in the frequency domain are successfully realized in a
      parameter range obtained in the theory.

PMID- 21069079
TI  - Data analysis of stellar specklegrams with neural networks.
AB  - An artificial neural network is applied to analysis of specklegrams of binary
      stars. Parameters of a binary star, the angular separation and the position
      angle, are estimated from the specklegrams by use of neural networks for each
      parameter. It is shown that a neural network is useful to analyze stellar
      specklegrams of binary stars.

PMID- 21069080
TI  - Covariance-based approach to texture processing.
AB  - We present a simple and effective approach for texture processing that uses the
      eigenfeatures of local covariance measures. The covariance measures act as a
      texton encoder, producing texture code that is invariant to local and global
      textural rotations. This method uses only six features obtained from two scales
      of the invariant encoder to generate numerical representations for roughness,
      anisotropy, and other higher-order textural features. Classification results for
      synthetic and natural textures are presented. We discuss the effect of window
      sizes used at local and global scales on the performance of the classifier.

PMID- 21069081
TI  - Image transfer by mutually pumped phase conjugators.
AB  - Cross talk is observed during the transient time of the photorefractive grating
      formation in a mutually pumped phase conjugator. We show that this feature can be
      used to transfer pictorial information from one location to another. The transfer
      is instantaneous and is demonstrated at a resolution of 6 lines/mm.

PMID- 21069082
TI  - Performance comparison between multiple-quantum-well modulator-based and vertical
      cavity-surface-emitting laser-based smart pixels.
AB  - We compared multiple-quantum-well modulator-based smart pixels and vertical
      cavity-surface-emitting laser (VCSEL) based smart pixels in terms of optical
      switching power, switching speed, and electric-power consumption. Optoelectronic
      circuits integrating GaAs field-effect transistors are designed for smart pixels
      of both types under the condition that each pixel has an optical threshold and
      gain. It is shown that both types perform maximum throughput of ~3 Tbps/cm(2). In
      regard to design flexibility, the modulator type is advantageous because
      switching time can be reduced by supplying large electric power, whereas
      switching time and electric-power consumption are limited to larger than certain
      values in the VCSEL type. In contrast, in regard to optical implementation, the
      VCSEL type is advantageous because it does not need an external bias-light
      source, whereas the modulator type needs bias-light arrays that must be precisely
      located because the small modulator diameter, <10 um, is essential to high-speed
      operation. A bias-light source that increases the total power consumption of the
      system may offset the advantages of the modulator type.

PMID- 21069083
TI  - Ho:YV0(4) solid-state saturable-absorber Q switch for a 2-um Tm,
      Cr:Y(3)Al(5)O(12) laser.
AB  - The holmium-doped yttrium orthovanadate (Ho:YVO(4)) crystal was shown to be an
      effective solid-state saturable-absorber Q switch for a flash-lamp-pumped
      Tm,Cr:Y(3)Al(5)O(12) laser operating at 2.017 um. A single Q-switched laser pulse
      of 3.5 mJ in energy and 45 ns in duration was observed with a 1-mm-thick 4%
      Ho:YVO(4) solid-state saturable absorber, which was grown with the high
      temperature-solution-growth method.

PMID- 21069084
TI  - Laser-induced darkening in thin films of fluorescein-doped boric acid glass.
AB  - We report laser-induced permanent darkening in thin films of fluorescein-doped
      boric acid glass. The photodarkening is accompanied by a substantial increase in
      the absorption of the irradiated samples. The photoinduced absorption appears to
      be permanent. Optical and electron paramagnetic resonance measurements suggest
      the creation of a new photochemical species on irradiation within the absorption
      band of the fluorescein molecule. A possible mechanism for the photochemical
      change responsible for the darkening is proposed. Optical storage of information
      through the formation of permanent holograms is demonstrated.

PMID- 21069085
TI  - High-power narrow-band pulses with wavelengths tunable about 1.053 um from a
      synchronously pumped optical parametric oscillator.
AB  - We have constructed an optical parametric oscillator to generate 75-ps near
      transform-limited pulses with wavelengths tunable about 1.053 um for use in pump
      probe studies of self-focusing. The singly resonant oscillator uses a Brewster
      cut LiB(3)O(5) crystal that is oriented for type-II phase matching and
      synchronously pumped by the amplified and frequency-tripled pulse trains from a
      mode-locked and Q-switched Nd:YLP laser. An intracavity Pockels cell is used to
      switch out single 0.5-MW pulses at rates of 1 to 10 Hz. The design, construction,
      and performance of the oscillator are discussed. Measured performance is compared
      with design predictions and with detailed numerical simulations.

PMID- 21069086
TI  - Optical and structural characterization of triallyl thiourea cadmium chloride
      (ATCC).
AB  - We report measurements of the structural and optical properties of triallyl
      thiourea cadmium chloride (ATCC). X-ray diffraction determined the point group to
      be 3 and the space group to be R3. ATCC is one of a series of semiorganic
      crystals that demonstrated good optical frequency conversion. We have
      investigated this material for its potential value in electro-optic and
      piezoelectric applications.

PMID- 21069087
TI  - Generation of H(2), O(2), and H(2)O(2) from water by the use of intense
      femtosecond laser pulses and the possibility of laser sterilization.
AB  - An intense femtosecond Ti-sapphire laser pulse was focused into water, leading to
      self-focusing. Apart from generating a white light (supercontinuum), the intense
      laser field in the self-focusing regions of the laser pulse dissociated the water
      molecules, giving rise to hydrogen and oxygen gas as well as hydrogen peroxide.
      Our analysis shows that the formation of free radicals O, H, and OH preceded the
      formation of the stable products of H(2), O(2), and H(2)O(2). Because O radicals
      and H(2)O(2) are strong oxydizing agents, one can take advantage of this
      phenomenon to design a laser scheme for sterilization in medical and biological
      applications.

PMID- 21069088
TI  - Mode-locked laser cavities with a single prism for dispersion compensation.
AB  - We demonstrate the use of a single prism for adjustable dispersion compensation
      in a mode-locked laser cavity, instead of the standard approach with a prism
      pair. A simple model based on the prism-pair configuration is presented to
      determine the group-velocity dispersion by use of ray optics to trace the
      wavelength-dependent optical axes through the cavity. We experimentally
      demonstrated this concept with a passively mode-locked diode-pumped Nd:glass
      laser producing 200-fs pulses with a 200-mW average output power, using only one
      intracavity prism. The advantages of such a cavity design are simple alignment,
      reduced loss, and lossless wavelength tunability This technique can be
      generalized to other angularly dispersive elements such as prismatic output
      couplers.

PMID- 21069089
TI  - Time-resolved photoluminescence measurements of InGaAs/ InP multiple-quantum-well
      structures at 1.3-um wavelengths by use of germanium single-photon avalanche
      photodiodes.
AB  - A commercially available germanium avalanche photodiode operating in the single
      photon-counting mode has been used to perform time-resolved photoluminescence
      measurements on InGaAs/lnP multiple-quantum-well structures. Photoluminescence in
      the spectral region of 1.3-1.48 um was detected with picosecond timing accuracy
      by use of the time-correlated single-photon counting technique. The carrier
      dynamics were monitored for excess photogenerated carrier densities in the range
      10(18)-10(15) cm(-3). The recombination time is compared for similar InGaAs-based
      quantum-well structures grown by use of different epitaxial processes.

PMID- 21069090
TI  - Faraday effect in standard optical fibers: dispersion of the effective Verdet
      constant.
AB  - We have measured the Faraday effect in silica standard optical fibers in the
      wavelength range 458-1523 nm. An effective Verdet constant Vef that exhibits a
      linear dependence on the square of the optical frequency nu is defined: V(ef) =
      (0.142 +/- 0.004) * 10(-28) nu(2) rad T(-1) m(-1). We demonstrate that the
      negative effects of a small linear birefringence can be minimized by adjustment
      of the input polarization to an optimum state.

PMID- 21069091
TI  - Single-mode GaAs/AIGaAs W waveguides with a low propagation loss.
AB  - We have designed a low-loss single-mode GaAs/AIGaAs optical waveguide with a
      symmetric five-layer heterostructure at the 1.31-um wavelength by use of an
      effective-index method. Waveguides with a W-shaped refractive-index profile have
      been grown by use of a metallo-organic chemical vapor deposition technique and
      fabricated with a chemical wet-etching method. Propagation loss has been measured
      by use of the Fabry-Perot resonance method and a sequential-cleaving experiment.
      The measured loss is as low as 0.19 dB/cm for waveguides with 2.3-um thickness
      and 4.3-um width, which is comparable to the lowest-loss semiconductor waveguides
      yet reported. These waveguides could be used to make low-loss modulators for
      guided-wave devices.

PMID- 21069092
TI  - Laser-induced predissociative fluorescence: dynamics and polarization and the
      effect of lower-state rotational energy transfer on quantitative diagnostics.
AB  - Laser-induced predissociative fluorescence is often used for diagnostics because
      its short-lived upper states are minimally disturbed by collisions. We discuss
      the effects of lower-state collisions with parameters relevant to our atmospheric
      H(2)-O(2) flame. A pulse of tunable KrF excimer-laser light induces the A ? X,
      Q(1)(11), 3 ? 0 transition in OH. We measure the intensity and the polarization
      of the resulting A ? X, Q(1)(11), 3 ? 2 fluorescence as a function of laser
      brightness. A simple model that uses no adjustable parameters produces a
      reasonable fit to the data. It predicts that, even at very modest laser energies,
      the fluorescence intensity is almost directly proportional to the rate constant
      for rotational energy transfer (RET) within the lower vibrational state. That
      rate constant can be a strong function of local conditions. Furthermore, under
      typical operating conditions the excimer will pump an amount of OH out of the
      lower state that is many times as large as that originally present. This occurs
      because RET within the X-state continuously replenishes the lower state during
      the laser pulse. Even when this occurs, the signal may still vary linearly with
      laser intensity, and the polarization may be nearly that expected for weak
      pumping. At the higher laser intensities, a significant fraction of the measured
      OH arises from two-photon photodissociation of the water from the flame reaction.

PMID- 21069093
TI  - Measurement capabilities of planar Doppler velocimetry using pulsed lasers.
AB  - Analytical models of a spectral filter that contains iodine vapor and of the
      noise sources associated with charge-coupled-device (CCD) detector technology are
      combined with a planar Doppler velocimetry (PDV) signal analysis to evaluate the
      measurement capabilities of PDV for quantitative aerodynamic research and
      production wind-tunnel testing applications. The criteria for optimizing the
      filter cell and calibrating the frequency scale of its transmission function are
      described. The measurement uncertainty limits owing to scientific-grade CCD
      detector performance are then evaluated, and an analysis is developed of the
      scattering properties of aerosols suitable for aerodynamic flow seeding. The
      combined results predict that single-pulse PDV measurements with velocity
      measurement uncertainties as small as 2 m/s should be possible in aerodynamic
      test facilities for measurement distances of tens of meters.

PMID- 21069094
TI  - Heating and destruction of metallic particles exposed to intense laser radiation.
AB  - The heating of a laser-irradiated solid aluminum particle to boiling or to
      temperatures that exceed boiling is analyzed theoretically and numerically by
      solution of the heat-transport equation. Two different criteria of particle
      destruction are considered. The temperature distributions inside the particles
      depending on the intensity values and particle sizes are presented. It is shown
      that at the start of heating the contribution of heat exchange plays the dominant
      role, but as the boiling point is approached the contribution of vaporization
      plays the main role.

PMID- 21069095
TI  - Prognosis for a mid-infrared magnetic rotation spectrometer for the in situ
      detection of atmospheric free radicals.
AB  - Mid-infrared magnetic rotation spectroscopy (MRS) experiments on nitric oxide
      (NO) are quantitatively modeled by theoretical calculations. The verified theory
      is used to specify an instrument that can make in situ measurements on NO and
      NO(2) in the Earth's atmosphere at a sensitivity level of a few parts in 10(12)
      by volume per second. The prototype instrument used in the experiments has an
      extrapolated detection limit for NO of 30 parts in 10(9) for a 1-s integration
      time over a 12-cm path length. The detection limit is an extrapolation of
      experimental results to a signal-to-noise ratio of one, where the noise is
      considered to be one-half the peak-to-peak baseline noise. Also discussed are the
      various factors that can limit the sensitivity of a MRS spectrometer that uses
      liquid-nitrogen-cooled lead-salt diode lasers and photovoltaic detectors.

PMID- 21069096
TI  - Onset of strong scintillation with application to remote sensing of turbulence
      inner scale.
AB  - Numerical simulation of propagation through atmospheric turbulence of an
      initially spherical wave is used to calculate irradiance variance sigma(2)(I),
      variance of log irradiance sigma(2)(ln I), and mean of log irradiance ?In I? for
      13 values of l(0)/R(f) (i.e., of turbulence inner scale l(0) normalized by
      Fresnel scale R(F)) and 10 values of Rytov variance sigma(2)(Rytov), which is the
      irradiance variance, including the inner-scale effect, predicted by perturbation
      methods; l(0)/R(f) was varied from 0 to 2.5 and sigma(2)(Rytov) from 0.06 to 5.0.
      The irradiance probability distribution function (PDF) and, hence, sigma(2)(I),
      sigma(2)(In I), and ?ln I? are shown to depend on only two dimensionless
      parameters, such as l(o)/R(F) and sigma(2)(Rytov). Thus the effects of the onset
      of strong scintillation on the three statistics are characterized completely.
      Excellent agreement is obtained with previous simulations that calculated
      sigma(2)(I). We find that sigma(2)(I), sigma(2)(In I), and ?ln I? are larger than
      their weak-scintillation asymptotes (namely, sigma(2)(Rytov), sigma(2)(Rytov),
      and - sigma(2)(Rytov)/2, respectively) for the onset of strong scintillation for
      all l(0)/R(f). An exception is that for the largest l(0)/R(f), the onset of
      strong scintillation causes sigma(2)(ln I) to decrease relative to its weak
      scintillation limit, sigma(2)(Rytov). We determine the efficacy of each of the
      three statistics for measurement of l(0), taking into account the relative
      difficulties of measuring each statistic. We find that measuring sigma(2)(I) is
      most advantageous, although it is not the most sensitive to l(0) of the three
      statistics. All three statistics and, hence, the PDF become insensitive to l(0)
      for roughly 1 < beta0(2) < 3 (where beta0(2) is sigma (2)(Rytov) for l(0) = 0);
      this is a condition for which retrieval of l(0) is problematic.

PMID- 21069097
TI  - The effects of Cannabis sativa L. seed (hempseed) in the ovariectomized rat model
      of menopause.
AB  - Cannabis sativa L. has been used for the treatment of various gynecological
      diseases in traditional medicine. The potential of this plant to protect against
      complications of menopause has been raised but rarely studied. Twenty female rats
      were divided into five groups: sham-operated (sham), ovariectomized (OVX) and
      three other ovariectomized groups: HST1%, HST2% and HST10% which received 1%, 2%
      and 10% hempseed, respectively, in their diet for 3 weeks. The effects of
      hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels
      were evaluated. Rats were tested for behavioral changes using the forced swimming
      test. The results showed that ovariectomy, independent of the type of diet,
      caused elevation of plasma calcium, total cholesterol and HDL-cholesterol levels,
      while hempseed modified this effect. Plasma estradiol levels were significantly
      lower in the OVX group compared to other groups. The swimming times for the OVX
      and sham groups were significantly shorter than that of the HSD10% group. All
      hempseed-treated groups were less anxious and showed significant declines in
      fecal boli compared to the sham group. The exploratory diving percent decreased
      in the HST10% group compared with other groups. These results suggest that
      hempseed may improve post-ovariectomy complications in rats.

PMID- 21069098
TI  - Characterization of cerebral salt wasting after subarachnoid hemorrhage model
      induced by endovascular puncture.
AB  - Cerebral salt wasting (CSW) frequently occurs concomitantly with an aneurysmal
      subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic
      diuresis, and reduces the total volume of blood. We previously reported that a
      rat model with SAH induced by endovascular puncture (EP) exhibited CSW.
      Therefore, we investigated the relationship between the spread of bleeding in the
      subarachnoid space and the intensity of CSW. We also investigated the development
      of CSW in different SAH models. SAH was induced by EP or by 0.3 mL of blood
      injection (BI) into the cisterna magna. To evaluate the occurrence of CSW, urine
      was cumulatively collected at the onset of SAH to 6 h later and analyzed for
      sodium (Na) excretion. SAH was classified from grade 1 (no bleeding) to grade 4
      (severe bleeding) based on the spread of bleeding in the subarachnoid space. In
      the EP model (SAH grade > 2) as the SAH grade increased, the volume of urine and
      Na excretion also significantly increased. Although the BI model rats exhibited
      SAH of grade 4, the volume of urine and Na excretion did not change. Therefore,
      our conclusion is that the spread of bleeding in the subarachnoid space may not
      cause CSW.

PMID- 21069099
TI  - Quantitative determination of atorvastatin and ortho-hydroxy atorvastatin in
      human plasma by liquid chromatography tandem mass spectrometry and
      pharmacokinetic evaluation.
AB  - A specific, sensitive and simple method was developed to determine the levels of
      both atorvastatin and ortho-hydroxy atorvastatin in human plasma. The analytes
      and internal standard pitavastatin were extracted from plasma by liquid-liquid
      extraction, separated on a Zorbax SB-C18 column, eluted with a mobile phase of
      water:acetonitrile (45:55 v/v), both containing 5% methanol and 0.01% formic
      acid. Detection was performed with an electrospray ionization triple quadrupole
      mass spectrometer in positive ion mode using multiple reaction monitoring. The
      standard calibration curves of atorvastatin and ortho-hydroxy atorvastatin were
      linear in the concentration range of 0.2-20 and 0.1-20 ng/mL, respectively. The
      intra- and inter-day precisions were < 7.7% and the accuracy was within +/- 5.9%.
      The method has been successfully used for the study of the pharmacokinetics of
      atorvastatin and ortho-hydroxy atorvastatin in Chinese patients with coronary
      heart disease after a single oral dose of 20 mg atorvastatin. The mean values for
      the area under the plasma concentration-time curve for atorvastatin and ortho
      hydroxy atorvastatin were 63.1 and 46.9 ng.h/mL, respectively.

PMID- 21069100
TI  - The use of in situ perfusion of the rat mesentery as a model to investigate
      vascular injury directly induced by drugs.
AB  - Exposure of the vasculature to vasodilators, pharmaceuticals and industrial
      chemicals may lead to injury of the blood vessel wall in animals. Vascular injury
      may begin with changes in the permeability of vascular endothelial cell and
      vessels, resulting in possible hemorrhage and edema leading subsequently to
      immune cell infiltration. The present study was undertaken to determine if the
      direct exposure of the Sprague Dawley rat mesenteric vasculature through the
      perfusion of aminophylline, fenoldopam, compound 48/80, histamine or serotonin
      has any such effects on the blood vessels, and if the two vital dyes Monastral
      blue B and Evans blue can be used to enhance the visualization of the vascular
      damage. Microscopic visualization was enhanced by the use of dyes and a variety
      of alterations of the perfused mesenteric vessels were detected, including
      varying degrees of mast cell degranulation, microvascular vasodilatation and
      increased vascular permeability. Macroscopic evidence of vascular damage was
      minimal. This study demonstrates that in situ perfusion of the rat mesentery is a
      simple and useful method to eliminate the influence of a variety of physiologic
      influences or homeostatic responses and can be used to further investigate drug
      induced vascular damage.

PMID- 21069101
TI  - Comparison of antiemetic efficacy between single and repeat treatment with
      dexamethasone in patients receiving carboplatin-based combination chemotherapy.
AB  - A retrospective study was carried out to compare the preventive effects of single
      and repeat treatment with dexamethasone (DEX) on delayed nausea and emesis in
      patients who had received carboplatin (CBDCA)-based combination chemotherapy.
      Sixty-four patients were evaluated. Efficacy was assessed using the nausea and
      emesis score, food intake score and the requirement for antiemetic medication.
      These forward scores were categorized as three-grade during the first 5 days
      after chemotherapy. Acute nausea and emesis were well controlled in both groups
      on day 1. Mean values of the nausea and emesis score on day 3 evening and the
      food intake score on day 4 morning in the repeat-treatment group was 1.31 +/-
      0.93 and 3.46 +/- 1.03, respectively, which were significantly better when
      compared with the single-treatment group (2.00 +/- 1.52; P = 0.028 and 2.79 +/-
      1.12; P = 0.018, respectively). Multivariate logistic regression analysis
      revealed that less frequent dispensing of antiemetic medication was significantly
      associated with the repeat-treatment group (adjusted odds ratio, 0.153; 95%
      confidence interval, 0.026-0.734; P = 0.018). These results suggest that repeat
      dose DEX may be more effective than single-dose DEX for the prevention of delayed
      nausea and emesis after CBDCA-based combination chemotherapy.

PMID- 21069102
TI  - Acceptability and tolerability of levetiracetam oral solution for the treatment
      of partial-onset seizures: the SOLUCION study.
AB  - This cross-sectional, observational study evaluated the use of levetiracetam oral
      solution in usual clinical practice. Patients >= 16 years with partial-onset
      seizures (had received levetiracetam oral solution for >= 28 days) completed a
      study questionnaire assessing overall acceptability of levetiracetam oral
      solution, specific organoleptic characteristics (taste, taste intensity,
      aftertaste), ease of use and convenience. Tolerability was assessed by evaluating
      adverse events. Of 389 patients, 92.8% (361/389) were evaluable for
      acceptability, all (389) for tolerability; 65.3% (236/361) rated levetiracetam
      oral solution very acceptable or acceptable, 41.5% (150/361) pleasant or very
      pleasant, 54.3% (196/361) neither strong nor mild taste intensity and indicated
      the drug left an aftertaste (most stated aftertaste did not bother them), 75.3%
      very easy or easy to use and 61.8% very convenient or convenient to use. There
      was a positive relationship between overall acceptability of levetiracetam oral
      solution and favorable responses for organoleptic characteristics, ease of use,
      convenience and patients' evaluation of treatment compliance (P < 0.0001 for
      each). Of the 176/353 who previously received another antiepileptic drug and
      reported preference for a medication, 72.2% (127/176) preferred levetiracetam
      oral solution and 39/389 (10%) reported adverse events. Levetiracetam oral
      solution demonstrated a high degree of patient acceptability in adult patients
      with partial-onset seizures and was well tolerated.

PMID- 21069103
TI  - Gateways to clinical trials.
AB  - Aclidinium bromide, AE-37, Alemtuzumab, AMA1-C1/ISA 720, Amlodipine
      besylate/atorvastatin calcium, Arachidonic acid, Arbaclofen placarbil,
      Aripiprazole, ARQ-621, Azelnidipine, Azilsartan medoxomil potassium; Bevacizumab,
      Biphasic insulin aspart, Bortezomib; Choriogonadotropin alfa, CTS-1027;
      Dapagliflozin, Dasatinib, Deforolimus, Degarelix acetate, Denufosol tetrasodium,
      Desvenlafaxine succinate, Dronedarone hydrochloride, Duloxetine hydrochloride,
      Dutasteride; Enfuvirtide, Entecavir, Etaracizumab, Everolimus, Exenatide,
      Ezetimibe; Ferric carboxymaltose, Fludarabine, Foretinib; Gefitinib, GFT-505, GSK
      256066; HPV-6/11/16/18, HuM195/rGel, HyperAcute-Lung cancer vaccine; I5NP,
      Imatinib mesylate, Imexon, Insulin detemir, Insulin glargine, Ivabradine
      hydrochloride; L2G7, Lacosamide, Lapatinib ditosylate, Lenalidomide,
      Lidocaine/prilocaine, Liposomal vincristine, Liraglutide, Lixivaptan;
      Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197
      conjugate vaccine, Methoxy polyethylene glycol-epoetin-beta, Mirabegron,
      Morphine/oxycodone, MR Vaccine, MSC-1936369B, Mycophenolic acid sodium salt;
      Narlaprevir, N-Desmethylclozapine; Ocriplasmin, Olaparib, Olmesartan medoxomil,
      Olmesartan medoxomil/azelnidipine, ONO-5334, ONO-8539; Palifermin, Panitumumab,
      Pardoprunox hydrochloride, PCV7, Peginterferon alfa-2a, Peginterferon alfa-2b,
      Pemetrexed disodium, Pexelizumab, PF-337210, Pitavastatin calcium; Raltegravir
      potassium, Recombinant interleukin-7, Regadenoson, Reniale, Roflumilast,
      Rosuvastatin calcium; Safinamide mesilate, SB-1518, SCH-527123, Selumetinib,
      Sipuleucel-T, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil,
      Talaporfin sodium, Tanespimycin, Technosphere/Insulin, Telaprevir, Telatinib,
      Telcagepant, Telmisartan/hydrochlorothiazide, Teriparatide, Testosterone
      transdermal gel, TH-302, Tiotropium bromide, Tocilizumab, Trabedersen,
      Tremelimumab; Valsartan/amlodipine besylate, Vernakalant hydrochloride,
      Visilizumab, Voreloxin, Vorinostat.

PMID- 21069104
TI  - Botulinum toxin: a poison transformed into a versatile tool.

PMID- 21069105
TI  - The parallel stratification masking technique: an analytical approach to
      predictably mask discolored dental substrate.
AB  - Discolored dental substrates continue to challenge the restorative team when
      ultraconservative treatment modalities are chosen. An innovative laboratory
      concept--the parallel stratification masking technique--has been developed in
      order to achieve maximum preservation of dental hard tissues and predictably
      accomplish a desirable esthetic outcome. The major advantages of this technique
      are that the ceramist is able to: a)identify and map the discolored dental
      substrate, b)predictably mask the discolored dental substrate, and c) assess the
      appropriate masking efficacy of the fabricated restoration prior to laboratory
      delivery to the dentist in cases of bonded porcelain restorations.

PMID- 21069106
TI  - Horizontal Ridge Augmentation Before Placing Implants Using a Double-bone, Double
      Resorbable Membrane Technique: Two Clinical Cases.
AB  - Guided bone regeneration is a well established technique used for augmentation of
      deficient alveolar ridges. There is much evidence in the procedure. Multiple
      techniques have been introduced using various types of membranes and bone grating
      materials. However, efficacious regeneration requires both a high level of
      technical skills and a through understanding of major biological principles. This
      case report is presented to illustrate a reliable approach to successful
      management of two different alveolar defects.

PMID- 21069107
TI  - The Healing of Free Gingival Autografts for Socket-seal Surgery: a Case Report.
AB  - Tooth extraction will be followed by marked alterations to the tissue volume, in
      particular in the anterior zone, which may jeopardize the esthetic outcome of any
      dental treatment involving tooth extraction. If, however, ridge collapse can eb
      prevented or minimized after tooth extraction, more predictable outcomes with
      superior esthetics can be accomplished along with fewer surgical procedures.
      Therefore, it was proposed that stabilizing the soft tissue architecture with a
      free gingival graft could minimize the soft tissue shrinkage. The following case
      report describes some surgical modifications and refinements in order to enhance
      the predictability of the socket-seal surgery.

PMID- 21069108
TI  - Evaluation of the effect of buccal corridor size on smile attractiveness.
AB  - INTRODUCTION: an attractive smile helps people feel more self-confident and look
      younger. One of the more controversial aspects of smile attractiveness pertains
      to buccal corridor size. There is no previous study by those with artistic
      knowledge that has assessed the asthetic considerations of buccal corridor size.
      The purpose of this study was to observe whether the size of buccal corridors has
      an impact on smile attractiveness evaluated by lay people, dental students, and
      art students. MATERIALS AND METHODS: colored post-treatment photograph with posed
      smiles of two subjects (one male, one female) were selected. The maxillary
      posterior dentitions were digitally altered to produce different buccal corridor
      sizes: narrow (28% buccal corridor), medium-narrow (22% buccal corridor), medium
      broad (10% buccal corridor), and broad (2% buccal corridor). The 5 images of each
      subject were paired into 11 possible combinations and presented to three group:
      art students, dental students, and lay people, who compared the two images in
      each pair of smile attractiveness. The statistical test used were Wilcoxon signed
      rank and Mann-Whitney test. RESULTS: minimal and excessive buccal corridors were
      the least attractive when judged by three groups. All groups preferred smaller
      buccal corridors for the male subject and larger buccal corridors for the female
      subject. No significant judging differences were found between male and female
      judges from among art and dental students. CONCLUSIONS: minimal or excessive
      buccal corridor should be included in the problem list during orthodontic
      diagnosis and treatment planning.

PMID- 21069109
TI  - Shear bond strength to enamel after power bleaching activated by different
      sources.
AB  - The purpose of the present study was to evaluate enamel bond strength of a
      composite resin material after hydrogen peroxide bleaching, activated by a diode
      laser (LaserSmile), an ozone device (HealOzone), a light-emitting diode (BT Cool
      whitening system), and a quartz-Plus. Fifty extracted caries-free permanent
      incisors were used in this study. Thirty-eight percent hydrogen peroxidegel was
      applied to sound, flattened labial enamel surfaces and activated by different
      sources. Enamel surfaces that had received no treatment were used as control
      samples. Bonding agent was applied according to the manufacturer's instructions
      and the adhesion test was performed according to ISO/TS 11405. Statistical
      analysis showed significant influence of the different activation technique of
      hydrogen peroxide on shear bond strength to enamel (ANOVA, LSD, P < 0.05). The
      data in this vitro explorative study suggest the activation of hydrogen peroxide
      by different sources may further affect the shear bond strength of subsequent
      composite resin restoration to enamel. Within the limitations of this in vitro
      study, further studies examining the structural changes of activated hydrogen
      peroxide-treated enamel are needed. Due to the different activation methods;
      duration of light irradiation effects, longer time periods may be needed before
      application of adhesive restorations to enamel, compared with non-activated
      bleaching.

PMID- 21069112
TI  - Are we ready for the big one? Lessons from a brief war that could apply to New
      Zealand primary health care services following a major disaster.

PMID- 21069110
TI  - In vitro study comparing fracture strength recovery of teeth restored with three
      esthetic bonding materials using different techniques.
AB  - Reattachment of the fractured fragment of a traumatized tooth (whenever available
      and usable) has become the treatment of choice in cases of uncomplicated crown
      fractures. Despite the presence of various bonding materials and techniques,
      laboratory data evaluating the biomechanical aspects of such procedures is
      largely lacking in the literature. The objective of this in vitro study was to
      evaluate the fracture strength recovery of incisors, following fragment
      restoration with three different techniques. A total of 90 extracted human
      maxillary central incisors were subjected to crown fractured under standard
      conditions. This was carried out by applying a compressive force from the buccal
      aspect of the clinical crown using a universal strength testing machine. The
      fractured teeth were equality distributed in three groups, defined on the basis
      of the technique used for reattachment: i) overcontour, ii) internal dentinal
      groove and iii) direct buildup. Each group was further subdivided into three
      subgroups on the basis of the intermediate restorative material used for
      reattachment, namely: i) hybrid composite (Filtek Z100 Universal Restorative, ii)
      nanocomposite (Filtek Z350) and iii) Ormocer (Voco Admira). Following
      reattachment, the crowns were re-fractured under standard conditions. The force
      required for fracture was recorded and was expressed as a percentage of the
      fracture strength of the intact tooth. The data was expressed as a percentage of
      the fracture strength of the intact tooth. The data was analyzed using two-way
      ANOVA and Bonferroni tests for pair-wise comparison. The results showed no
      statistically significant differences in fractures strength between the three
      groups (P > 0.05). However, comparison of the subgroups revealed statistically
      significant higher strength recovery percentages for the hybrid and the
      nanocomposite compared with the Ormocer material (P < 0.05). It was concluded
      that material properties have a significant influence on the success of
      reattachment procedures.

PMID- 21069113
TI  - Relationship between decile score of secondary school, the size of town of origin
      and career intentions of New Zealand medical students.
AB  - INTRODUCTION: New Zealand is facing a general practice workforce crisis,
      especially in rural communities. Medical school entrants from low decile schools
      or rural locations may be more likely to choose rural general practice as their
      career path. AIM: To determine whether a relationship exists between secondary
      school decile rating, the size of the town of origin of medical students and
      their subsequent medical career intentions. METHODS: University of Auckland
      medical students from 2006 to 2008 completed an entry questionnaire on a range of
      variables thought important in workforce determination. Analyses were performed
      on data from the 346 students who had attended a high school in New Zealand.
      RESULTS: There was a close relationship between size of town of origin and decile
      of secondary school. Most students expressed interests in a wide range of
      careers, with students from outside major cities making slightly fewer choices on
      average. DISCUSSION: There is no strong signal from these data that career
      specialty choices will be determined by decile of secondary school or size of
      town of origin. An increase in the proportion of rural students in medical
      programmes may increase the number of students from lower decile schools, without
      adding another affirmative action pathway.

PMID- 21069114
TI  - HPV/cervical cancer vaccination: parental preferences on age, place and
      information needs.
AB  - INTRODUCTION: A vaccine against cervical cancer is available in New Zealand
      through school and primary care for girls aged 12-18 years. Factors that might
      increase or hinder widespread uptake by the target population need to be
      identified. AIM: To describe parents' preferences on where their daughter(s)
      receive the human papillomavirus (HPV) vaccine, at what age, and their
      information needs. METHODS: 3123 questionnaires were distributed to parents
      recruited from 14 schools in 2008, prior to the start of the school-based
      vaccination programme. Outcome measures were: preferred age and place of
      vaccination, and information needs of parents and their daughters. Tests for
      significance were performed to determine whether parental preferences differed by
      ethnic group (Maori, Pacific, New Zealand European and 'Other'). RESULTS: A 25%
      response rate was achieved (769/3123). Receipt of the HPV vaccine in a clinic
      setting was preferred by 40% of parents; 25% preferred vaccination at school.
      Fifty percent preferred vaccination to occur at age 13 or older; 28% thought ages
      10, 11 or 12 appropriate. One in three parents wanted more information and 65%
      said they would seek information from their family doctor before deciding on the
      vaccine for their daughter(s). DISCUSSION: We suggest that a programme delivered
      jointly in primary care and school settings, that is appropriately resourced for
      follow-up and information-sharing, would increase vaccine coverage. The rationale
      for vaccination at age 12 needs to be made clear to parents and evidence-based
      information needs to be delivered appropriately to parents and girls.

PMID- 21069115
TI  - Increasing the uptake of opportunistic chlamydia screening: a pilot study in
      general practice.
AB  - INTRODUCTION: Genitourinary Chlamydia trachomatis infection is common and
      associated with considerable personal and public health cost. Effective detection
      strategies are needed. AIM: To assess feasibility of an opportunistic
      incentivised chlamydia screening programme in general practice over six months.
      METHODS: This study was designed as a pilot for a randomised controlled trial in
      primary care. Three general practices were randomly allocated to intervention
      (two practices) and control groups. The intervention involved practice education,
      self-sample collection and practice incentives (funding and feedback) for a three
      month 'active' intervention period. Feedback and education was discontinued
      during the second three-month period. Practice-specific nurse- or doctor-led
      strategies were developed for identifying, testing, treating and recalling male
      and female patients aged 16-24 years. The main outcome measure was the difference
      between the practices' chlamydia screening rates over the six months following
      introduction of the intervention, controlling for baseline rates from the
      previous year. RESULTS: Chlamydia testing rates during the year prior to the
      intervention ranged from 2.9% to 7.0% of practice attendances by 16-24-year-olds.
      The intervention practices had higher rates of screening compared with the
      control practice (p<0.001) at three months, but both practices reverted to pre
      intervention rates by six months. The nurse-led screening strategy was more
      effective (35% declining to 5.5% over six months) than the doctor-led strategy
      (15% declining to 1.6% over six months) (p=0.04). DISCUSSION: Incentivised
      opportunistic chlamydia screening of 16-24-year-old patients attending their
      general practitioner with a programme involving practice education, feedback and
      self-sample collection can increase screening rates.

PMID- 21069116
TI  - General practitioners' views about diagnosing and treating depression in Maori
      and non-Maori patients.
AB  - INTRODUCTION: The study investigated general practitioners' (GPs') views about
      recognising and treating depression among patients to establish possible reasons
      for reported lower levels of diagnosis and treatment of depression among Maori
      compared to non-Maori patients. METHODS: Semi-structured interviews with 23 GPs
      in the Auckland region, including both Maori and non-Maori GPs, elicited GPs'
      views about risk factors for depression, recognising depression and circumstances
      in which GPs would prescribe medication or recommend other treatments for
      depression. FINDINGS: A framework was developed which incorporated the strategies
      GPs reported using to diagnose and treat depression. This consisted of three
      categories: (a) how depression is identified, (b) factors influencing treatment
      decisions, and (c) treatment outcomes. Reasons reported by GPs as most likely to
      lead to ethnic differences in diagnosing depression were greater stigma relating
      to admitting depression among Maori patients, Maori patients being less likely to
      talk about being depressed, and the need for patients to have effective
      communication with their GP. Effective communication, where Maori patients felt
      free to talk about personal feelings, was more likely when there was an
      established relationship between the GP and patient. CONCLUSION: The findings are
      consistent with previous reports that depression is less likely to be diagnosed
      by GPs among Maori patients, compared to non-Maori patients. GPs who are able to
      establish effective communication with patients, gain their trust and take
      account of the reluctance of some Maori patients to talk about personal feelings,
      are more likely to diagnose and treat depression effectively.

PMID- 21069118
TI  - General practitioner perceptions of clinical medication reviews undertaken by
      community pharmacists.
AB  - INTRODUCTION: Delivery of current health care services focuses on
      interdisciplinary teams and greater involvement of health care providers such as
      nurses and pharmacists. This requires a change in role perception and acceptance,
      usually with some resistance to changes. There are few studies investigating the
      perceptions of general practitioners (GPs) towards community pharmacists
      increasing their participation in roles such as clinical medication reviews.
      There is an expectation that these roles may be perceived as crossing a clinical
      boundary between the work of the GP and that of a pharmacist. METHODS: Thirty
      eight GPs who participated in the General Practitioner-Pharmacists Collaboration
      (GPPC) study in New Zealand were interviewed at the study conclusion. The GPPC
      study investigated outcomes of a community pharmacist undertaking a clinical
      medication review in collaboration with a GP, and potential barriers. The GPs
      were exposed to one of 20 study pharmacists. The semi-structured interviews were
      recorded and transcribed verbatim then analysed using a general inductive
      thematic approach. FINDINGS: The GP balanced two themes, patient outcomes and
      resource utilisation, which determined the over-arching theme, value. This
      concept was a continuum, depending on the balance. Factors influencing the theme
      of patient outcomes included the clinical versus theoretical nature of the
      pharmacist recommendations. Factors influencing resource utilisation for general
      practice were primarily time and funding. CONCLUSION: GPs attributed different
      values to community pharmacists undertaking clinical medication reviews, but this
      value usually balanced the quality and usefulness of the pharmacist's
      recommendations with the efficiency of the system in terms of workload and
      funding.

PMID- 21069117
TI  - Perspectives on adherence to blood pressure-lowering medications among Samoan
      patients: qualitative interviews.
AB  - AIM: To explore influences on adherence to taking long-term medications among
      Samoan patients in an Auckland general practice. METHODS: Twenty Samoan
      participants from an Auckland general practice were identified and interviewed
      about their views on adherence or non-adherence to taking blood pressure-lowering
      medications. One-to-one semi-structured interviews using open-ended questions
      were undertaken in Samoan and English, recorded, transcribed and translated into
      English. Transcriptions were examined by two researchers to identify themes.
      FINDINGS: Patients with 'high' and 'lower' rates of adherence to taking usual
      medication were identified using medication possession ratio cut-offs from
      medical records of timely prescribing. Ten participants with 'high' and 10 with
      'lower' rates of adherence were interviewed, including 11 women and nine men.
      Themes identified for those with lower adherence included 'lack of transport',
      'family commitments', 'forgetfulness', 'church activities', 'feeling well' and
      'priorities'. Themes identified for those with high rates of adherence included
      'prioritising health', 'previous event', 'time management', 'supportive family
      members' and 'relationship with GP (language and trust)'. A theme common to both
      was 'coping with the stress of multiple comorbidities'. CONCLUSION: Reasons for
      adherence and non-adherence to taking blood pressure-lowering medications among
      the Samoan patients interviewed were multifactorial and encompass personal,
      social, cultural and environmental factors. Interdisciplinary teams to support
      treatment decisions (including Pacific health professionals or community health
      workers), systematic identification of those with low rates of adherence, phone
      or text follow-up, use of church or family networks, provision of transport where
      needed and better tools and resources may help address this problem.

PMID- 21069119
TI  - Community pharmacist perceptions of clinical medication reviews.
AB  - INTRODUCTION: Changes in delivery of health care services has led to pressure for
      community pharmacists to extend their traditional role and become more involved
      with patient-focussed services such as medication reviews, in collaboration with
      general practitioners (GPs). This has not been generally implemented into routine
      practice, and many barriers have been suggested that inhibit community
      pharmacists extending their role. These have often focussed on physical or
      functional barriers. This study explores possible attitudinal factors that
      prevent increased participation of community pharmacists in medication reviews
      undertaken in collaboration with GPs. METHODS: Twenty community pharmacist
      participants who participated in the General Practitioner-Pharmacist
      Collaboration (GPPC) study were interviewed. The GPPC study investigated the
      outcomes of community pharmacists undertaking a clinical medication review in
      collaboration with GPs, and the potential barriers. Semi-structured interviews
      were analysed using a general inductive thematic approach. FINDINGS: Emerging
      themes were that community pharmacists perceived that they were not mandated to
      undertake this role, it was not a legitimate role, particularly from the business
      perceptive, and pharmacists were concerned that they lacked the skills and
      confidence to provide this level of input. CONCLUSION: While there is concern
      that community pharmacists' skills are underutilised, there are probable
      attitudinal barriers inhibiting pharmacists from increasing their role in
      clinical medication reviews. Perceived legitimacy of the service was a dominant
      theme, which appeared to be related to issues in the business model. Further
      investigation should consider the use of a clinical pharmacist working within a
      general practice independent of a community pharmacy.

PMID- 21069120
TI  - Reducing health disparities for low decile children and families: a nurse-led
      response.
AB  - BACKGROUND AND CONTEXT: Reducing health disparities for children living in
      deprived areas has been difficult to achieve. This paper describes the
      implementation of a nurse-led, child-specific clinic within a general practice
      setting to improve health outcomes for high needs Maori/Pacific Island and
      NZDep96 quintile groups 4 and 5 children and their whanau/families. ASSESSMENT OF
      PROBLEM: The medical centre that implemented the clinic had a high number of
      enrolled children with chronic and recurrent morbidities. Children frequently did
      not attend clinic appointments, and there was high use of after-hours services.
      RESULTS: An outcome audit after 18 months demonstrated a significant (>30%)
      reduction in eczema severity, daily irritability, and daily occurrence of pain.
      Post-intervention fewer children were hospitalised and there was a 50% reduction
      in antibiotic use. STRATEGIES FOR IMPROVEMENT: The aim of the nurse-led clinic
      was to improve health gains, facilitate morbidity control of chronic conditions,
      and to offer prevention strategies to promote wellness for the target population.
      The reduction of morbidity severity by 10% was measured with specific morbidity
      scoring systems for eczema, constipation and nocturnal enuresis. Other outcome
      indicators measured vomiting/reflux, wheezing/coughing, constipation/soiling,
      irritability, sleep disturbances, hospital admissions, and antibiotic use.
      LESSONS: Nurse-led clinics facilitated by nurses with advanced skills can reduce
      health disparities for the target population. The amount of time the nurse is
      able to spend with the child and whanau/family, and the provision of
      opportunistic assessments as required, has effected positive change in those
      children most in need.

PMID- 21069121
TI  - Sometimes a case can be made for physician-assisted suicide: yes.

PMID- 21069122
TI  - Sometimes a case can be made for physician-assisted suicide: no.

PMID- 21069123
TI  - Noni (Morinda citrifolia L.). Also known as great morinda, Indian mulberry,
      nunaakai, dog dumpling, mengkudu, beach mulberry, vomit fruit and cheese fruit.

PMID- 21069124
TI  - Work stories.

PMID- 21069125
TI  - We should not screen for ADHD.

PMID- 21069126
TI  - A well designed journal for the primary care sector.

PMID- 21069127
TI  - Too many articles by nurses.

PMID- 21069128
TI  - Development of high-performance supercapacitor electrodes using novel ordered
      mesoporous tungsten oxide materials with high electrical conductivity.
AB  - An ordered mesoporous WO(3-x) material was employed for use as a supercapacitor
      electrode. This material exhibited a high rate capability and an excellent
      capacitance (366 MUF cm(-2), 639 F cm(-3)), which were probably attributed to the
      large ordered mesopores, high electrical conductivity, and high material density.

PMID- 21069129
TI  - Synthesis of 4(5)-phenacyl-imidazoles from isoxazole side-chain rearrangements.
AB  - A novel base-induced rearrangement of isoxazoles into imidazole derivatives is
      reported. In the isoxazole series, this represents the first example of a three
      atom side-chain rearrangement involving a CNC sequence. The reactions are carried
      out under nitrogen and produced 2-aryl-4(5)-phenacyl-5(4)-phenyl-imidazoles in
      high yields. In the presence of oxygen, a cascade rearrangement-oxidation
      reaction sequence was observed and imidazole derivatives bearing an oxidized side
      chain were isolated.

PMID- 21069139
TI  - 2009 International Symposium on Metallomics.

PMID- 21069140
TI  - Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma
      mass spectrometry (LA-ICP-MS) and metallomics.
AB  - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been
      developed and established as an emerging technique in the generation of
      quantitative images of metal distributions in thin tissue sections of brain
      samples (such as human, rat and mouse brain), with applications in research
      related to neurodegenerative disorders. A new analytical protocol is described
      which includes sample preparation by cryo-cutting of thin tissue sections and
      matrix-matched laboratory standards, mass spectrometric measurements, data
      acquisition, and quantitative analysis. Specific examples of the bioimaging of
      metal distributions in normal rodent brains are provided. Differences to the
      normal were assessed in a Parkinson's disease and a stroke brain model.
      Furthermore, changes during normal aging were studied. Powerful analytical
      techniques are also required for the determination and characterization of metal
      containing proteins within a large pool of proteins, e.g., after denaturing or
      non-denaturing electrophoretic separation of proteins in one-dimensional and two
      dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein
      bands or spots separated after gel electrophoresis. MALDI-MS can then be used to
      identify specific metal-containing proteins in these bands or spots. The
      combination of these techniques is described in the second section.

PMID- 21069142
TI  - Metalloproteomics, metalloproteomes, and the annotation of metalloproteins.
AB  - Metalloproteomics includes approaches that address the expression of
      metalloproteins and their changes in biological time and space. Metalloproteomes
      are investigated by a combination of approaches. Experimental approaches include
      structural genomics, which provides insights into the architecture of metal
      binding sites in metalloproteins and establishes ligand signatures from the types
      and spacings of the metal ligands in the protein sequence. Theoretical approaches
      employ these ligand signatures as templates for homology searches in sequence
      databases. In this way, the number of metalloproteins in the iron, copper, and
      zinc metalloproteomes in various phyla of life has been estimated. Yet, manganese
      metalloproteomes remain poorly defined. Metals have catalytic and structural
      functions in proteins. However, additional functions have evolved. Proteins that
      control metal homeostasis and proteins that are metal-regulated bind metal ions
      transiently and are generally not accounted for in estimates from bioinformatics.
      Thus, metalloproteomes are dynamic and likely to be larger than present estimates
      suggest. This account discusses the assignment of transition metals in
      metalloproteins and the ensuing issues facing analytical chemists and structural
      and computational biologists. Biological and chemical selectivities render metal
      selection by metalloproteins either more stringent or less stringent depending on
      the metal homeostatic system of the organism, the subcellular location of the
      protein, and environmental factors. Failure to recognize the principles of metal
      utilization has led to assigning the wrong metal in metalloproteins and has
      missed some of the regulatory functions of transition metal ions.

PMID- 21069143
TI  - Dynamic pathways of selenium metabolism and excretion in mice under different
      selenium nutritional statuses.
AB  - The selenoprotein, cellular glutathione peroxidase (cGPx), has an important role
      in protecting organisms from oxidative damage through reducing levels of harmful
      peroxides. The liver and kidney in particular, have important roles in selenium
      (Se) metabolism and Se is excreted predominantly in urine and feces. In order to
      characterize the dynamics of these pathways we have measured the time-dependent
      changes in the quantities of hepatic, renal, urinary, and fecal Se species in
      mice fed Se-adequate and Se-deficient diets after injection of (82)Se-enriched
      selenite. Exogenous (82)Se was transformed to cGPx in both the liver and kidney
      within 1 h after injection and the synthesis of cGPx decreased 1 to 6 h and
      continued at a constant level from 6 to 72 h after injection. The total amount of
      Se associated with cGPx in mice fed Se-deficient diets was found to be less than
      in mice fed Se-adequate diets. This finding indicated that cGPx synthesis was
      suppressed under Se-deficient conditions and did not recover with selenite
      injection. Excess Se was associated with selenosugar in liver and transported to
      the kidney within 1 h after injection, and then excreted in urine and feces
      within 6 h after injection. Any excess amount of Se was excreted mainly as a
      selenosugar in urine.

PMID- 21069141
TI  - Targeting selenium metabolism and selenoproteins: novel avenues for drug
      discovery.
AB  - Selenoproteins play a wide range of roles in metabolism and oxidative stress
      defense and are produced by organisms in all three domains of life. Recent
      evidence has been presented that metal based cancer drugs target the selenol
      nucleophile of the active site selenocysteine in thioredoxin reductase
      isoenzymes. Other metals and metalloids, such as tin, arsenic and gold, have also
      recently been shown to form stable complexes with hydrogen selenide, a required
      precursor for the synthesis of selenoproteins in all biological organisms.
      Moreover these metal based compounds have been shown to inhibit growth of
      pathogens such as Clostridium difficile and Treponema denticola due to their
      reactivity with this highly reactive metabolic precursor. This review summarizes
      the recent finding on these two avenues for drug discovery, and puts this work in
      context with the larger field of selenium biology.

PMID- 21069144
TI  - A proteome investigation of roxarsone degradation by Alkaliphilus oremlandii
      strain OhILAs.
AB  - Clostridial species predominate in both chicken gastrointestinal tract as well as
      litter where the organoarsenical roxarsone (3-nitro 4-hydroxybenzenearsonic acid)
      is anaerobically transformed releasing the more recognized toxic inorganic
      arsenic. 2D-gel electrophoresis and mass spectrometry were used to evaluate the
      changes in protein expression of Alkaliphilus oremlandii in response to different
      growth conditions (e.g., terminal electron acceptors) in order to explore the
      mechanism of microbial biotransformation of roxarsone. Aldehyde ferredoxin
      oxidoreductase, the enzyme that belongs to the xanthine oxidase family of
      molybdoenzymes was significantly overexpressed in the presence of roxarsone
      suggesting a role in the anaerobic metabolism of this substituted nitrophenol.

PMID- 21069145
TI  - Ribonucleoside labeling with Os(VI): a methodological approach to evaluation of
      RNA methylation by HPLC-ICP-MS.
AB  - Covalent modifications of nucleobases are thought to play an important role in
      regulating the functions of DNA and various cellular RNA types. Perhaps the best
      characterized is DNA methylation on cytosine (methyl tag attached to carbon 5
      position) and such modification has also been detected in stable and long-lived
      RNA molecules. In this work, we propose a novel procedure enabling very sensitive
      quantification of methylcytidine and other ribonucleosides, based on reversed
      phase liquid chromatography with inductively coupled plasma mass spectrometry
      (ICP-MS) detection. The procedure relies on labeling ribose residues with osmium,
      by formation of a ternary complex between cis-diol ribose groups, hexavalent
      osmium (K(2)OsO(2)(OH)(4)) and tetramethylethylenediamine (TEMED). The
      derivatization reaction was carried out with 50 : 1 molar excess of Os to
      ribonucleoside, pH 4, for 2 h at room temperature. The structures of Os-labeled
      cytidine and methylcytidine were confirmed by electrospray ionization mass
      spectrometry. The separation of Os-labeled cytidine (C), uridine (U), 5
      methylcytidine (5mC) and guanosine (G) was achieved on C18 column (Gemini, 150 *
      3 mm, 5 MUm) with isocratic elution (0.05% triethylamine + 6 mmol L(-1) ammonium
      acetate, pH 4.4: methanol (85 : 15)) and a total flow rate 0.6 mL min(-1). The
      column effluent was on-line introduced to ICP-MS (a model 7500 ce, Agilent
      Technologies) for specific detection at (189)Os. Calibration was performed within
      the concentration range 0-200 nmol L(-1) of each ribonucleoside and the
      analytical figures of merit were evaluated. For 100 MUL injection, the detection
      limits for C, U, 5mC, G were 24, 38, 21 and 28 pmol L(-1), respectively. While
      introducing Os(vi)-TEMED to the column, it eluted in the dead volume and the
      detection limit for osmium was 20 pmol L(-1). The results obtained in this work
      might be helpful in the analysis of RNA digests, providing quantitative data on
      the ribonucleoside composition and RNA methylation (measured as the percentage of
      methylated cytidines with respect to total RNA cytidines).

PMID- 21069146
TI  - Selenium speciation profiles in selenite-enriched soybean (Glycine Max) by HPLC
      ICPMS and ESI-ITMS.
AB  - Soybean (Glycine Max) plants were grown in soil supplemented with sodium
      selenite. A comprehensive selenium profile, including total selenium
      concentration, distribution of high molecular weight selenium and
      characterization of low molecular weight selenium compounds, is reported for each
      plant compartment: bean, pod, leaf and root of the Se-enriched soybean plants.
      Two chromatographic techniques, coupled with inductively coupled plasma mass
      spectrometry (ICPMS) for specific selenium detection, were employed in this work
      to analyze extract solutions from the plant compartments. Size-exclusion
      chromatography revealed that the bean compartment, well-known for its strong
      ability to make proteins, produced high amounts (82% of total Se) of high
      molecular weight selenospecies, which may offer additional nutritional value and
      suggest high potential for studying proteins containing selenium in plants. The
      pod, leaf and root compartments primarily accumulate low molecular weight
      selenium species. For each compartment, low molecular weight selenium species
      (lower than 5 kDa) were characterized by ion-pairing reversed phase HPLC-ICPMS
      and confirmed by electrospray ionization ion trap mass spectrometry (ESI-ITMS).
      Selenomethionine and selenocystine are the predominant low molecular weight
      selenium compounds found in the bean, while inorganic selenium was the major
      species detected in other plant compartments.

PMID- 21069147
TI  - Simultaneous multiple element detection by particle beam/hollow cathode-optical
      emission spectroscopy as a tool for metallomic studies: determinations of metal
      binding with apo-transferrin.
AB  - Particle beam/hollow cathode-optical emission spectroscopy (PB/HC-OES) is
      presented as a tool for the determination of metal ion loading in transferrin
      (Tf). The elemental specificity of optical emission spectroscopy provides a means
      of assessing metal ion concentrations as well as the relative amounts of metal
      per unit protein concentration (up to 2 moles of Fe per mole of protein). The
      PB/HC-OES method allows for the simultaneous detection of metal content (Fe (I)
      371.99, Ni (I) 341.41 nm, Zn (I) 213.86 nm, and Ag (I) 338.28 nm in this case),
      as well as elemental carbon and sulfur (C (I) 156.14 nm and S (I) 180.73 nm) that
      are reflective of the protein composition and concentration. Quantification for
      the metal species is based on calibration functions derived from aqueous
      solutions, with limits of detection for the entire suite being less than 1.0 MUM.
      Determinations in this manner eliminate much of the ambiguity inherent in UV-VIS
      absorbance determinations of Tf metal binding. Validation of this method is
      obtained by analyzing loading response of Fe(3+) into Tf using the PB/HC-OES
      method and comparing the results with those of the standard UV-VIS absorbance
      method. Maximum Fe(3+) loading of Tf (based on the number of available binding
      sites) was determined to be 71.2 +/- 4.7% by the PB/HC-OES method and 67.5 +/-
      2.5% for the UV-VIS absorbance method. Element emission ratios between the dopant
      metals and the carbon and sulfur protein constituents allow for concentration
      independent determinations of metal binding into Tf. Loading percentages were
      determined for Ni(2+), Zn(2+), and Ag(+) into Tf with maximum loading values of
      19.5 +/- 0.4%, 41.0 +/- 4.4%, and 141.2 +/- 4.3%, respectively. While of no
      apparent biological significance, Ag(+) presents an interesting case as a
      surrogate for Pt(2+), whose binding with Tf has shown to be quite different from
      the other metals. A different mode from the others is indeed observed, and is
      consistent with conjecture on the Pt(2+) mechanisms. Competitive binding studies
      not easily performed using absorbance spectroscopy are easily performed by
      simultaneous, multielement analysis, reflective of the metals and the protein
      content. In this work, there is clear competition between and Fe(3+) and Zn(2+)
      for binding in the C-terminus lobe of Tf, while Ni(2+) binds within the N
      terminus lobe. Addition of Ag(+) to this mixture does not affect the other
      metals' distributions, but reflects binding at other protein sites.

PMID- 21069148
TI  - In vivo bioavailability of selenium in enriched Pleurotus ostreatus mushrooms.
AB  - The in vivo bioavailability of Se was investigated in enriched Pleurotus
      ostreatus mushrooms. A bioavailability study was performed using 64 Wistar male
      rats separated in 8 groups and fed with different diets: without Se, with
      mushrooms without Se, with enriched mushrooms containing 0.15, 0.30 or 0.45 mg
      kg(-1) Se and a normal diet containing 0.15 mg kg(-1) of Se using sodium
      selenate. The experiment was performed in two periods: depletion (14 days) and
      repletion (21 days), according to the Association of Official Analytical
      Chemists. After five weeks, the rats were sacrificed under carbon dioxide, and
      blood was drawn by heart puncture. Blood plasma was separated by centrifugation.
      The total Se concentration in the plasma of rats fed with enriched mushrooms was
      higher than in rats fed with a normal diet containing sodium selenate. The plasma
      protein profiles were obtained using size exclusion chromatography (SEC) and UV
      detectors. Aliquots of effluents (0.5 mL per minute) were collected throughout in
      the end of the chromatographic column. However, Se was determined by graphite
      furnace atomic absorption spectrometry (GF AAS) only in the aliquots where
      proteins were detected by SEC-UV. The plasma protein profile of rats fed with
      different diets was similar. The highest Se concentration was observed in a
      peptide presenting 8 kDa. Furthermore, the higher Se concentration in this
      peptide was obtained for rats fed with a diet using enriched mushrooms (7 MUg L(
      1) Se) compared to other diets (2-5 MUg L(-1) Se). These results showed that Se
      enriched mushrooms can be considered as an alternative Se food source for humans,
      due to their high bioavailability.

PMID- 21069149
TI  - Formation of methylselenol, dimethylselenide and dimethyldiselenide in in vitro
      metabolism models determined by headspace GC-MS.
AB  - The aim of this study was to identify the presence of MeSeH in metabolic
      reactions. An analytical method based on direct headspace GC-MS, eliminating loss
      of volatile species during sample pretreatment procedures, was developed for this
      purpose. The in vitro conversion of selenium compounds to the volatile species
      methylselenol, MeSeH, dimethyl selenide, DMeSe and dimethyl diselenide, DMeDSe
      was investigated. The analytical method was evaluated by means of standards of
      dimethyl diselenide, dimethyl selenide. The corresponding sulfides were found
      unsuitable as internal standards as they interacted with the selenides. The limit
      of detection was 0.25 MUmol L(-1) (20 MUg L(-1)) for the selenide as well as the
      diselenide. Formation of MeSeH was not observed in significant amount when
      selenomethionine was incubated with the enzyme l-methionine-gamma-lyase; instead
      large amounts of DMeDSe were formed. In aqueous solution, methylseleninic acid,
      MeSeA reacted spontaneously with glutathione, GSH to form DMeDSe. In strongly
      reducing environments, however, MeSeH was also observed. When the formed MeSeH
      was trapped with iodoacetic acid, no DMeDSe was detected indicating that DMeDSe
      formation was due to spontaneous oxidation of MeSeH. These findings imply that
      DMeDSe may be a marker for the production of MeSeH in in vitro models. When
      MeSeA, Se-methylselenocysteine, Se-MeSeCys and SeMet were incubated with Jurkat
      cells, DMeDSe formation was only observed in the case of MeSeA. Trace amounts of
      DMeSe was observed in the vial with MeSeA as well as Se-MeSeCys. When DMeSe and
      DMeDSe were added to plasma, the sensitivity of only DMeDSe decreased
      significantly, implicating that DMeDSe underwent a reaction with plasma hindering
      the volatilization. This emphasizes that results from in vitro selenium
      metabolism studies may not be uncritically interpreted as consistent with the in
      vivo reality.

PMID- 21069156
TI  - Metalloproteins and neuronal death.
AB  - Neurodegenerative diseases include Alzheimer's and Parkinson's disease that are
      very common and other diseases that are notorious but occur less often such as
      Creutzfeldt-Jakob disease. In each case a protein is closely linked to the
      pathology of these diseases. These proteins include alpha-synuclein, the prion
      protein and Abeta. Despite first being discovered because of aggregates of these
      amyloidogenic proteins found in the brains of patients, these proteins all exist
      in the healthy brain where their normal function involves binding of metals.
      Recognition of these proteins as metalloproteins implies that the diseases they
      are associated with are possibly diseases with altered metal metabolism at their
      heart. This review considers the evidence that cell death in these diseases
      involves not just the aggregated proteins but also the metals they bind.

PMID- 21069157
TI  - Zinc-dependent effects of small molecules on the insulin-sensitive transcription
      factor FOXO1a and gluconeogenic genes.
AB  - Metal-binding compounds have recently been reported to have anti-hyperglycaemic
      properties in vivo. In the current study, we have investigated the ability of
      these compounds and related structures to induce insulin-like signal transduction
      to downstream effectors such as the transcription factor FOXO1a and the key
      gluconeogenic regulatory enzymes phosphoenolpyruvate carboxykinase (PEPCK) and
      glucose 6-phosphatase (G6Pase). Our results indicate that beta-thujaplicin,
      diethyldithiocarbamate (DEDTC) and its clinically-used dimer disulfiram, induce
      insulin-like dose-dependent effects on signalling to FOXO1a in a manner that is
      strictly dependent on the presence of zinc ions, as other ions including
      aluminium, cobalt, copper, lithium and manganese cannot substitute. The most
      potent compound tested on gluconeogenesis is disulfiram, which in the presence of
      10 MUM zinc, inhibited both PEPCK and G6Pase with an IC50 of 4 MUM. Our results
      demonstrate that metal-binding compounds with diverse structures can induce zinc
      dependent insulin-like effects on signal transduction and gene expression.

PMID- 21069158
TI  - Biodistribution and long-term fate of silver nanoparticles functionalized with
      bovine serum albumin in rats.
AB  - Silver nanocrystals (Ag NCs) hold promising antibiotic and antiviral properties
      in biological systems. The biodistribution of silver nanostructures injected into
      animals in vivo is currently unknown, remaining as a fundamental issue for
      potential therapeutic applications. Here, we injected Ag NCs capped with bovine
      serum albumin (BSA) in live rats to elucidate their fate in several organs
      including liver, heart and brain. Very significant accumulations of nanoparticles
      were confirmed by inductively coupled plasma mass spectroscopy (ICPMS) and
      transmission electron microscopy (TEM) techniques on the liver and heart. In
      contrast, the brain tissue did not reveal evidence of particles content. Our
      results suggest that Ag+ permeated across the blood-brain barrier (BBB), and
      followed swift clearance from the organ.

PMID- 21069160
TI  - Complexes of hydroxy(thio)pyrone and hydroxy(thio)pyridinone with Zn(II) and
      Mo(VI). Thermodynamic stability and insulin-mimetic activity.
AB  - The development of metal-containing pharmaceuticals as insulin-mimetics has been
      the object of recent worldwide research. We have examined a series of zinc(II)
      and molybdenum(VI) complexes with model O,S-donor ligands (thiomaltol and 1,2
      dimethyl-3-hydroxypyridine-4-thione (DMHTP)) and the corresponding O,O-analogues
      (maltol and DMHP) for their insulin-mimetic activity. Aimed at getting structure
      activity relationships, some physical-chemical properties were also studied, such
      as metal-complex formation, speciation at different pH conditions and ligand
      lipophilicity. The Zn-complexes exhibit considerably higher insulin-mimetic
      activity than the corresponding Mo-analogues. Particularly, the
      bis(thiomaltolato)zinc(II) complex reveals a very high activity, ascribed to the
      effect of the thione pi character and to the soft nature of the sulfur donor atom
      enhancing the Zn(II)-ligand affinity and the ligand/complex lipophilicity, two
      determinant parameters for delivering the metal-drug into the cells. Hence, these
      preliminary studies indicate that the Zn(thiomaltol)2 complex can be considered a
      potential drug candidate for treatment of diabetes mellitus, upon in vivo
      evaluations.

PMID- 21069167
TI  - Raman spectroscopy a promising technique for investigations of metallothioneins.
AB  - Metallobiomolecules are highly elaborated coordination complexes, and their
      fundamental metal-ligand interactions are critical components of metalloprotein
      folding, assembly, stability, electrochemistry, and catalytic function. Herein,
      we have described the benefits in using Raman spectroscopy to define the metal
      ion binding properties of MTs toward metal ions such as Zn(ii) and Cd(ii). In
      particular, this vibrational technique can shed light on the secondary structures
      eventually present in MTs and the ligands involved in metal coordination. The
      oxidation state of Cys residues and their participation in the metal chelation
      can be clearly defined, as well as the eventual involvement of His residues. With
      regards to exogenous metal ligands such as sulfide anions, their presence can be
      identified by some marker bands whose intensity is linearly correlated with
      sulfide/metal molar ratio. Finally, Raman can be also an useful tool for
      providing information on the favourite sites of the radical attack and radical
      induced modification in protein folding. In conclusion, many advantages such as
      the capability of defining local regions in large complexes and detecting several
      structural features at the same time, the ability in supporting mechanisms, as
      well as the requirement of low sample amount, make to propose Raman spectroscopy,
      in coupling with analytical techniques such as atomic emission spectroscopy, gas
      chromatography, and circular dichroism, as one of the most promising experimental
      strategies in the research on structure-activity relationships in MTs.

PMID- 21069159
TI  - Trivalent arsenicals and glucose use different translocation pathways in
      mammalian GLUT1.
AB  - Rat glucose transporter isoform 1 or rGLUT1, which is expressed in neonatal heart
      and the epithelial cells that form the blood-brain barrier, facilitates uptake of
      the trivalent arsenicals arsenite as As(OH)3 and methylarsenite as CH3As(OH)2.
      GLUT1 may be the major pathway for arsenic uptake into heart and brain, where the
      metalloid causes cardiotoxicity and neurotoxicity. In this paper, we compare the
      translocation properties of GLUT1 for trivalent methylarsenite and glucose.
      Substitution of Ser(66), Arg(126) and Thr(310), residues critical for glucose
      uptake, led to decreased uptake of glucose but increased uptake of CH3As(OH)2.
      The K(m) for uptake of CH3As(OH)2 of three identified mutants, S66F, R126K and
      T310I, were decreased 4-10 fold compared to native GLUT1. The osmotic water
      permeability coefficient (P(f)) of GLUT1 and the three clinical isolates
      increased in parallel with the rate of CH3As(OH)2 uptake. GLUT1 inhibitors
      Hg(II), cytochalasin B and forskolin reduced uptake of glucose but not
      CH3As(OH)2. These results indicate that CH3As(OH)2 and water use a common
      translocation pathway in GLUT1 that is different to that of glucose transport.

PMID- 21069168
TI  - In vivo micro X-ray analysis utilizing synchrotron radiation of the gametophytes
      of three arsenic accumulating ferns, Pteris vittata L., Pteris cretica L. and
      Athyrium yokoscense, in different growth stages.
AB  - In vivo X-ray analysis utilizing synchrotron radiation was performed to
      investigate the distribution and oxidation state of arsenic in the gametophytes
      of two hyperaccumulators, Pteris vittata L. and Pteris cretica L., and an arsenic
      accumulating fern, Athyrium yokoscense in the several growth stages from
      germination. The distribution of arsenic in P. vittata changed through the
      development of the plant tissues as follows. In two-week-old gametophyte, arsenic
      was mainly present along the rhizoid. In the one-month-old gametophyte with
      reproductive organs, arsenic was accumulating uniformly in the sheet of cells,
      except in the reproductive area. After fertilization, arsenic was observed in the
      aboveground part of the sporophyte structures. P. cretica and A. yokoscense
      showed different distributions, respectively. P. cretica showed an accumulation
      of arsenic in the reproductive area, in contrast to P. vittata, before
      fertilization, while arsenic was observed in the aboveground part of the
      sporophyte after fertilization. A. yokoscense showed an accumulation of arsenic
      along the rhizoids before fertilization, while it was present mainly along the
      roots of the sporophyte after fertilization. Reduced arsenic (As(iii)) was
      observed in all stages and in all tissues of P. vittata gametophytes. Further, a
      reduction of arsenic was commonly observed among the three ferns, although
      arsenic was bounded to sulfur in A. yokoscense. These findings may be related to
      their own reproductive process or to detoxification mechanism. They provide basic
      information for the understanding of arsenic hyperaccumulation in these ferns,
      leading to further application of these gametophyte systems.

PMID- 21069169
TI  - An electrospray/inductively coupled plasma dual-source time-of-flight mass
      spectrometer for rapid metallomic and speciation analysis. Part 1. Molecular
      channel characterization.
AB  - A new time-of-flight mass spectrometer has been developed that uses an
      electrospray source and an inductively coupled plasma to extract molecular,
      atomic, and isotopic information simultaneously from a single sample. This paper
      will focus on characterization of the ESI channel. Sensitivities are reported for
      hexadecyltrimethylammonium, tetrahexylammonium, tetraoctylammonium, myoglobin,
      insulin, cyanocobalamin, leucine enkephalin, and alcohol dehydrogenase. Skimmer
      nozzle collisionally induced dissociation is explored for adduct removal and
      analyte fragmentation on the ESI channel for tetraoctylammonium ion and leucine
      enkephalin. Long-term and short-term spray stability is also examined.

PMID- 21069170
TI  - An electrospray/inductively coupled plasma dual-source time-of-flight mass
      spectrometer for rapid metallomic and speciation analysis. Part 2. Atomic channel
      and dual-channel characterization.
AB  - A new Time-of-Flight Mass Spectrometer (TOFMS) has been developed that employs an
      electrospray source and an inductively coupled plasma simultaneously to provide
      molecular, structural, atomic, and isotopic information from a sample. This paper
      will focus on characterization of the ICP source and will demonstrate
      simultaneous operation of the two sources. Preliminary sensitivities and limits
      of detection for Cr, Co, Ga, As, Ag, Cs, Ho, Hg, Tl, and Bi on the ICP channel
      are reported. Long-term stability and drift of the ICP channel are also
      discussed. Simultaneous operation of both channels is demonstrated for
      cyanocobalamin, myoglobin, and superoxide dismutase.

PMID- 21069171
TI  - Synthesis and biodistribution of [99mTc]-N-[4-nitro-3-trifluoromethyl-phenyl]
      cyclopentadienyltricarbonyltechnetium carboxamide, a nonsteroidal antiandrogen
      flutamide derivative.
AB  - In our efforts to develop a novel class of SPECT imaging agents based on
      nonsteroidal androgen receptor (AR) antagonists, we have synthesized N
      cyclopentadienyltricarbonyltechnetium-N-[4-nitro-3-trifluoromethyl-phenyl]
      carboxamide (NF(99m)Tc), an analog of the AR antagonist ligand flutamide.
      NF(99m)Tc was obtained in 82% yield from the reaction of N-[4-nitro-3
      trifluoromethyl-phenyl]-ferrocenecarboxamide (NFFe) with fac
      [(99m)Tc(H(2)O)(3)(CO)(3)](+) in DMF-water at pH 1 and at 150  degrees C for 1 h.
      The corresponding Re analog was also prepared. In vitro assays demonstrated high
      stability of NF(99m)Tc under physiological conditions, buffer and blood. The
      tissue biodistribution in mature male Wistar rats showed a significant selective
      uptake by prostate but this uptake was not blocked by an excess of testosterone
      acetate. A higher uptake by lung tissues was observed.

PMID- 21069178
TI  - Cytosolic zinc buffering and muffling: their role in intracellular zinc
      homeostasis.
AB  - Our knowledge of the molecular mechanisms of intracellular homeostatic control of
      zinc ions is now firmly grounded on experimental findings gleaned from the study
      of zinc proteomes and metallomes, zinc transporters, and insights from the use of
      computational approaches. A cell's repertoire of zinc homeostatic molecules
      includes cytosolic zinc-binding proteins, transporters localized to cytoplasmic
      and organellar membranes, and sensors of cytoplasmic free zinc ions. Under steady
      state conditions, a primary function of cytosolic zinc-binding proteins is to
      buffer the relatively large zinc content found in most cells to a cytosolic
      zinc(ii) ion concentration in the picomolar range. Under non-steady state
      conditions, zinc-binding proteins and transporters act in concert to modulate
      transient changes in cytosolic zinc ion concentration in a process that is called
      zinc muffling. For example, if a cell is challenged by an influx of zinc ions,
      muffling reactions will dampen the resulting rise in cytosolic zinc ion
      concentration and eventually restore the cytosolic zinc ion concentration to its
      original value by shuttling zinc ions into subcellular stores or by removing zinc
      ions from the cell. In addition, muffling reactions provide a potential means to
      control changes in cytosolic zinc ion concentrations for purposes of cell
      signalling in what would otherwise be considered a buffered environment not
      conducive for signalling. Such intracellular zinc ion signals are known to derive
      from redox modifications of zinc-thiolate coordination environments, release from
      subcellular zinc stores, and zinc ion influx via channels. Recently, it has been
      discovered that metallothionein binds its seven zinc ions with different
      affinities. This property makes metallothionein particularly well positioned to
      participate in zinc buffering and muffling reactions. In addition, it is well
      established that metallothionein is a source of zinc ions under conditions of
      redox signalling. We suggest that the biological functions of transient changes
      in cytosolic zinc ion concentrations (presumptive zinc signals) complement those
      of calcium ions in both spatial and temporal dimensions.

PMID- 21069179
TI  - Distinct uptake of tellurate from selenate in a selenium accumulator, Indian
      mustard (Brassica juncea).
AB  - Tellurium (Te) is widely used in industry because of its unique chemical and
      physical properties, and has recently become a part of everyday life as a
      component of phase-change optical magnetic disks. However, the recovery of Te
      from the environment has not been discussed yet. In this regard, we evaluated the
      potential use of Indian mustard (Brassica juncea), a selenium (Se) accumulator,
      for the phytoremediation of Te. The Indian mustard plant was exposed to selenate
      and tellurate and the concentrations of Se and Te and the chemical species in the
      plant were determined. The Indian mustard plant accumulated less Te than Se, and
      the amount of Te accumulated in the plant was approximately 1/69 of that of Se.
      Although the incorporation of selenate was reduced by increasing sulfate
      concentration in the medium, the incorporation of Te was not affected by it,
      suggesting that this plant was able to discriminate tellurate from selenate in
      the roots. Three Te species were detected in the plant. The major species was
      tellurate. The other two species were not identical to available Te standards and
      thus could not be identified. Consequently, the Indian mustard plant is
      inappropriate for the phytoremediation of Te because it can strictly distinguish
      tellurate from selenate.

PMID- 21069180
TI  - Protein phosphorylation studies of cerebral spinal fluid for potential biomarker
      development.
AB  - Subarachnoid hemorrhage (SAH) followed by cerebral vasospasm (CV) leads to severe
      debilitation or death of an estimated one million people worldwide every year. A
      biomarker that would predict the onset of CV after a SAH would be useful in
      informing treatment protocols, but has yet to be found. The focus of this study
      is to explore differences in protein phosphorylation in cerebral spinal fluid
      (CSF) among healthy patients, SAH patients and SAH-CV patients. A significant
      difference in phosphorylation among the three sample types could be an important
      step towards the discovery of a diagnostic marker. The identification and
      validation of phosphorylated protein differences for study is manifested in the
      nature of signaling involved in the pathological events seen post SAH. Capillary
      liquid chromatography (cap-LC) coupled to inductively coupled plasma mass
      spectrometry (ICPMS) and nano-liquid chromatography-CHIP/ion trap mass
      spectrometry (nanoLC-CHIP/ITMS) are used to identify and measure protein
      phosphorylation changes in the CSF of the aforementioned groups. ICPMS represents
      a suitable method for screening ultra-trace phosphorus levels at the natural
      isotope, (31)P, while nano-LC-CHIP/ITMS is used to identify phosphoproteins by
      searching appropriate protein databases.

PMID- 21069211
TI  - Room temperature oxidation of methyl orange and methanol over Pt-HCa2Nb3O10 and
      Pt-WO3 catalysts without light.
AB  - The layered semiconductor Pt-HCa(2)Nb(3)O(10) can catalyze room temperature air
      oxidation of methyl orange. It is also more effective than Pt-WO(3) in catalyzing
      reaction of methanol with air. Pt-HCa(2)Nb(3)O(10) could find wide application as
      a mild oxidizing catalyst.

PMID- 21069212
TI  - Molecular assembly of two [Co(II)4] linear arrays.
AB  - Molecular chains of four Co(II) ions stabilized by a bis-beta-diketone/pyridyl
      ligand may be isolated or linked into molecular pairs of two semi-independent
      such units.

PMID- 21069213
TI  - Directing energy transfer in discrete one-dimensional oligonucleotide-templated
      assemblies.
AB  - Monodisperse DNA-templated one dimensional dye assemblies have been constructed
      in which the energy transfer can be directed. Fluorescence experiments suggest an
      optimum transfer efficiency for stacks of 30 bases long.

PMID- 21069214
TI  - Mitochondrial biofuel cells: expanding fuel diversity to amino acids.
AB  - Although mitochondria have long been considered the powerhouse of the living
      cell, it is only recently that we have been able to employ these organelles for
      electrocatalysis in electrochemical energy conversion devices. The concept of
      using biological entities for energy conversion, commonly referred to as a
      biofuel cell, has been researched for nearly a century, but until recently the
      biological entities were limited to microbes or isolated enzymes. However, from
      the perspectives of efficient energy conversion and high volumetric catalytic
      activity, mitochondria may be a possible compromise between the efficiency of
      microbial biofuel cells and the high volumetric catalytic activity of enzymatic
      biofuel cells. This perspective focuses on comparing mitochondrial biofuel cells
      to other types of biofuel cells, as well as studying the fuel diversity that can
      be employed with mitochondrial biofuel cells. Pyruvate and fatty acids have
      previously been studied as fuels, but this perspective shows evidence that amino
      acids can be employed as fuels as well.

PMID- 21069215
TI  - Solving the spectroscopic phase: imaging excited wave packets and extracting
      excited state potentials from fluorescence data.
AB  - We develop an inversion scheme for obtaining the signs of transition-dipole
      amplitudes from fluorescence line intensities. Using the amplitudes thus obtained
      we show how to extract highly accurate excited state potential(s) and the
      transition-dipole(s) as a function of inter-nuclear displacements. The same
      dipole amplitudes can also be used to extract the phase and amplitude of unknown
      time-evolving wave packets, in essentially a quantum non-demolition manner. The
      procedure, which is demonstrated for the A((1)?) and B((1)Pi(u)) states of the
      Na(2) molecule, is shown to yield reliable results even when we are given
      incomplete or uncertain data. We also demonstrate the success of our approach in
      extracting double minimum potentials. The inversion scheme is in principle
      applicable to any polyatomic molecule.

PMID- 21069216
TI  - Ultrafast dynamics through conical intersections and intramolecular vibrational
      energy redistribution in styrene.
AB  - We report a femtosecond time-resolved photoelectron spectroscopy (TRPES)
      investigation of internal conversion in the first two excited singlet electronic
      states of styrene. We find that radiationless decay through an S(1)/S(0) conical
      intersection occurs on a timescale of ~4 ps following direct excitation to S(1)
      with 0.6 eV excess energy, but that the same process is significantly slower (~20
      ps) if it follows internal conversion from S(2) to S(1) after excitation to S(2)
      with 0.3 eV excess energy (0.9 eV excess energy in S(1)).

PMID- 21069217
TI  - Organocatalytic asymmetric direct vinylogous aldol reactions of gamma
      crotonolactone with aromatic aldehydes.
AB  - The direct aldol reaction of gamma-crotonolactone and various aromatic aldehydes
      is catalyzed by bifunctional aminothiourea and aminosquaramide organocatalysts to
      provide diastereomerically and enantiomerically enriched 5-substituted 2(5H)
      furanones (gamma-butenolides). The reaction is a simple alternative to the
      classical vinylogous aldol reaction of silyloxy furans.

PMID- 21069218
TI  - Design and development of quantum dots and other nanoparticles based cellular
      imaging probe.
AB  - One goal of nanotechnology is to prepare cellular nanoprobes for various
      biological applications where conventional molecular probes fall short of long
      term stability and simultaneous detection of multiple signals. Successful
      development of cellular nanoprobes requires the availability of a library of
      functional nanoparticles, knowledge of their interactions with cells and
      mechanism of cellular entry and to modulate these interactions by appropriate
      design of surface functionality. Although a great deal of research has been done
      in past 15 years, only limited success has been achieved in live cell labeling
      with high specificity, sub-cellular targeting and single molecule trafficking.
      This article focuses on the author's effort in making cellular imaging nanoprobes
      from different nanoparticles and discusses the most critical issues in the
      context of current knowledge, such as different variables that often influence
      labeling, non-specific binding/uptake of nanoprobes and specific live cell
      labeling. Finally, the important role of coating chemistry to overcome these
      problems has been highlighted and some successful labeling results have been
      summarized.

PMID- 21069219
TI  - Chemical gardens from silicates and cations of group 2: a comparative study of
      composition, morphology and microstructure.
AB  - We have compared the behaviour of the chloride salts of the cations Ca(2+),
      Sr(2+) and Ba(2+) of Group 2 of the Periodic Table in the formation of chemical
      gardens in silicate solutions. We performed analyses of morphology, composition
      and microstructure using environmental scanning electron microscopy (ESEM), X-ray
      diffraction (XRD) and energy dispersive X-ray analysis (EDX). We have identified
      different growth regimes in these salts (jetting and budding), which are
      dependent on the concentration of the silicate solution. The behaviour is similar
      for all the cations but reactivity decreases down the group and is directly
      proportional to the solubility of the salts: Ca(2+) > Sr(2+) > Ba(2+).

PMID- 21069220
TI  - PEG-POSS assisted facile preparation of amphiphilic gold nanoparticles and
      interface formation of Janus nanoparticles.
AB  - A general approach to transfer water-soluble nanoparticles with different shapes,
      sizes, and surface charges into organic solvents, retaining their surface charge
      properties was developed, and its application in fabrication of hybrid Janus
      particles with opposite charges in solution was also demonstrated.

PMID- 21069222
TI  - Strategy for preparation of hybrid polymer hydrogels using silica nanoparticles
      as multifunctional crosslinking points.
AB  - Novel hybrid polymer hydrogels were prepared in a facile manner by simple mixing
      of a water-soluble copolymer having trimethoxysilyl side chains with silica
      nanoparticles used as multiple crosslinkers.

PMID- 21069221
TI  - Synthesis of photoluminescent carbogenic dots using mesoporous silica spheres as
      nanoreactors.
AB  - A novel and facile approach for preparing hydrophilic carbogenic dots (CDs) has
      been developed with mesoporous silica spheres as nanoreactors by using an
      impregnation method. The resulting highly efficient photoluminescent CDs without
      any further treatment are monodisperse, photostable and of low toxicity, and show
      excellent luminescence properties.

PMID- 21069223
TI  - Dynamic microporous indium(III)-4,4'-oxybis(benzoate) framework with high
      selectivity for the adsorption of CO2 over N2.
AB  - Presented here is a dynamic microporous indium(III)-4,4'-oxybis(benzoate)
      framework material constructed from dual flexible building units, showing high
      selectivity for the adsorption of CO(2) over N(2).

PMID- 21069224
TI  - Phosphorus run-off assessment in a watershed.
AB  - The Watershed Assessment Model was used to simulate the runoff volume, peak
      flows, and non-point source phosphorus loadings from the 5870 km(2) Lake
      Okeechobee watershed as a case study. The results were compared to on-site
      monitoring to verify the accuracy of the method and to estimate the
      observed/simulated error. In 2008, the total simulated phosphorus contribution
      was 9634, 6524 and 3908 kg (P) y(-1) from sod farms, citrus farms and row crop
      farmlands, respectively. Although the dairies represent less than 1% of the total
      area of Kissimmee basin, the simulated P load from the dairies (9283 kg (P) y(-1)
      in 2008) made up 5.4% of the total P load during 2008. On average, the modeled P
      yield rates from dairies, sod farms and row crop farmlands are 3.85, 2.01 and
      0.86 kg (P) ha(-1) y(-1), respectively. The maximum sediment simulated phosphorus
      yield rate is about 2 kg (P) ha(-1) and the particulate simulated phosphorus
      contribution from urban, improved pastures and dairies to the total phosphorus
      load was estimated at 9%, 3.5%, and 1%, respectively. Land parcels with P
      oversaturated soil as well as the land parcels with high phosphorus assimilation
      and high total phosphorus contribution were located. The most critical sub-basin
      was identified for eventual targeting by enforced agricultural best management
      practices. Phosphorus load, including stream assimilation, incoming to Lake
      Okeechobee from two selected dairies was also determined.

PMID- 21069225
TI  - Fluorous silica gel-supported perfluoro-tagged palladium nanoparticles: an
      efficient and reusable catalyst for direct C-2 arylation of indoles.
AB  - The preparation of FSG-supported palladium nanoparticles and their application in
      direct C-2 arylation of indoles are presented. Moderate to good yields were
      obtained with ultra-low catalyst loading. The catalyst could be easily recovered
      by simple workup and reused up to seven runs with only a slight decrease in its
      activity.

PMID- 21069226
TI  - Gold nanoparticles supported on TiO2 catalyse the cycloisomerisation/oxidative
      dimerisation of aryl propargyl ethers.
AB  - Gold nanoparticles supported on TiO(2) (~1%) catalyse in high yields the
      selective cycloisomerisation of aryl propargyl ethers into the corresponding 2H
      chromenes, under heterogeneous conditions. 2H,2'H-3,3'-Bichromenes resulting from
      a catalytic oxidative dimerization pathway are also formed as by-products.

PMID- 21069227
TI  - Temperature dependent selective gas sorption of the microporous metal-imidazolate
      framework [Cu(L)] [H2L = 1,4-di(1H-imidazol-4-yl)benzene].
AB  - A highly stable copper(II) microporous framework with cylindrical channels
      constructed from 1,4-di(1H-imidazol-4-yl)benzene (H(2)L) and CuCl(2).2H(2)O is
      composed of Cu(II)-imidazolate tubes interconnected by the 1,4-phenylene group of
      L(2-), and shows temperature dependent selective gas sorption properties.

PMID- 21069228
TI  - Empirical force fields for complex hydrated calcio-silicate layered materials.
AB  - The use of empirical force fields is now a standard approach in predicting the
      properties of hydrated oxides which are omnipresent in both natural and
      engineering applications. Transferability of force fields to analogous hydrated
      oxides without rigorous investigations may result in misleading property
      predictions. Herein, we focus on two common empirical force fields, the simple
      point charge ClayFF potential and the core-shell potential to study tobermorite
      minerals, the most prominent family of Calcium-Silicate-Hydrates that are complex
      hydrated oxides. We benchmark the predictive capabilities of these force fields
      against first principles results. While the structural information seem to be in
      close agreement with DFT results, we find that for higher order properties such
      as elastic constants, the core-shell potential quantitatively improves upon the
      simple point charge model, and shows a larger degree of transferability to
      complex materials. In return, to remedy the deficiencies of the simple point
      charge potential for hydrated calcio-silicates, we suggest using both structural
      data and elasticity data for potential calibration, a new force field potential,
      CSH-FF. This re-parameterized version of ClayFF is then applied to simulating an
      atomistic model of cement (Pellenq et al., PNAS, 2009). We demonstrate that this
      force field improves the predictive capabilities of ClayFF, being considerably
      less computational intensive than the core-shell model.

PMID- 21069229
TI  - Nitrogen defects from NH3 in rare-earth sesquioxides and ZrO2.
AB  - Effects of nitrogen defects on the electrical properties of RE(2)O(3) (RE = Nd,
      Gd, Er, Y) and ZrO(2) have been investigated by equilibration in ammonia (NH(3))
      atmospheres in the temperature range 1000-1200  degrees C. The electrical
      conductivity in ammonia corresponded to that in H(2)-Ar mixtures of similar
      pO(2). However, upon replacing ammonia with an inert gas, the conductivity
      increases abruptly, typically one order of magnitude, before gradually returning
      to its equilibrium value. A defect model based on dissolution and dissociation of
      effectively neutral imide defects substituting oxide ions, NH, is proposed to
      describe this behavior. Conductivity measurements are interpreted in terms of
      nitrogen acceptors which are passivated by protons in the presence of H(2)(g),
      and subsequently compensated by positive charge carriers in an inert atmosphere
      as out-diffusion of hydrogen leaves an effective acceptor, N. In the case of
      Y(2)O(3), a NH concentration of 0.7 mol% was estimated from quantification of the
      nitrogen and hydrogen contents of a sample quenched in NH(3).

PMID- 21069230
TI  - Reverse engineering of metabolic networks, a critical assessment.
AB  - Inferring metabolic networks from metabolite concentration data is a central
      topic in systems biology. Mathematical techniques to extract information about
      the network from data have been proposed in the literature. This paper presents a
      critical assessment of the feasibility of reverse engineering of metabolic
      networks, illustrated with a selection of methods. Appropriate data are simulated
      to study the performance of four representative methods. An overview of sampling
      and measurement methods currently in use for generating time-resolved
      metabolomics data is given and contrasted with the needs of the discussed reverse
      engineering methods. The results of this assessment show that if full inference
      of a real-world metabolic network is the goal there is a large discrepancy
      between the requirements of reverse engineering of metabolic networks and
      contemporary measurement practice. Recommendations for improved time-resolved
      experimental designs are given.

PMID- 21069231
TI  - The kinetics and mechanisms of amorphous calcium carbonate (ACC) crystallization
      to calcite, via vaterite.
AB  - The kinetics and mechanisms of nanoparticulate amorphous calcium carbonate (ACC)
      crystallization to calcite, via vaterite, were studied at a range of
      environmentally relevant temperatures (7.5-25  degrees C) using synchrotron-based
      in situ time-resolved Energy Dispersive X-ray Diffraction (ED-XRD) in conjunction
      with high-resolution electron microscopy, ex situ X-ray diffraction and infrared
      spectroscopy. The crystallization process occurs in two stages; firstly, the
      particles of ACC rapidly dehydrate and crystallize to form individual particles
      of vaterite; secondly, the vaterite transforms to calcite via a dissolution and
      reprecipitation mechanism with the reaction rate controlled by the surface area
      of calcite. The second stage of the reaction is approximately 10 times slower
      than the first. Activation energies of calcite nucleation and crystallization are
      73+/-10 and 66+/-2 kJ mol(-1), respectively. A model to calculate the degree of
      calcite crystallization from ACC at environmentally relevant temperatures (7.5-40
      degrees C) is also presented.

PMID- 21069232
TI  - Medium-bridged lactams: a new class of non-planar amides.
AB  - Medium-bridged twisted lactams, in which a non-planar amide bond is achieved by
      incorporating the nitrogen atom at the bridgehead position in a medium-sized
      heterocycle, offer an attractive setting in which to study the properties of
      distorted amide linkages. This Emerging Area article will describe progress in
      the preparation and study of these compounds. This work shows that compounds
      containing an even moderately distorted amide bond display useful and unusual
      chemical properties while retaining a measure of stability that enables their
      study.

PMID- 21069233
TI  - O,O-dimethylthiophosphonosulfenyl bromide-silver triflate: a new powerful
      promoter system for the preactivation of thioglycosides.
AB  - O,O-Dimethylthiophosphonosulfenyl bromide (DMTPSB) in combination with silver
      triflate provides a powerful thiophilic promoter system. Both "armed" and
      "disarmed" thioglycoside glycosyl donors can be activated to form glycosidic
      linkages efficiently by the pre-activation protocol. The usefulness of this new
      promoter is illustrated by a successful iterative one-pot oligosaccharide
      assembly.

PMID- 21069234
TI  - Wilsoniamines A and B: novel alkaloids from the temperate Australian bryozoan,
      Amathia wilsoni.
AB  - Two novel alkaloids, wilsoniamines A and B, both possessing a
      hexahydropyrrolo[1,2-c]imidazol-1-one ring system that has not previously been
      found in nature, together with a new alkaloid, amathamide H and a known alkaloid,
      amathamide C were isolated from the temperate Australian bryozoan, Amathia
      wilsoni. MS and NMR analysis established the structure of the new compounds and
      indicated that the structure of amathamide C and several related compounds be
      revised. Amathamides C and H showed moderate anti-malarial and anti-trypanosomal
      activity.

PMID- 21069235
TI  - DBU-catalyzed transprotection of N-Fmoc-cysteine di- and tripeptides into S-Fm
      cysteine di- and tripeptides.
AB  - The transprotection of N-Fmoc-cysteine containing di- and tripeptides possessing
      a free SH group to produce the corresponding S-Fm-cysteine di- and tripeptides
      bearing a free amino group is accomplished efficiently with DBU in dry THF. The N
      Fmoc to S-Fm transformation mechanism is discussed. S-Fm-Cysteine di- and
      tripeptides readily form amide bonds on coupling with N-(Pg-alpha
      aminoacyl)benzotriazoles and N-(Pg-alpha-dipeptidoyl)benzotriazoles to give
      larger peptides.

PMID- 21069236
TI  - Design synthesis and photocatalytic activity of a novel lilac-like silver
      vanadate hybrid solid based on dicyclic rings of [V4O12]4- with {Ag7}7+ cluster.
AB  - An unusual two-dimensional bicyclic [V(4)O(12)](4-)-based coordination polymer
      with a novel maximum {Ag(7)}(7+) cluster and containing five crystallographically
      independent silver atoms was obtained and showed good photocatalytic activity for
      the degradation of methylene blue.

PMID- 21069237
TI  - Rhodium complexes bearing tetradentate diamine-bis(phenolate) ligands.
AB  - Using tetradentate, dianionic ligands, several new rhodium complexes have been
      prepared. Some of these diamine-bis(phenolate) compounds, are active for C-H
      activation of benzene. These complexes are air and thermally stable. All four
      complexes were characterized by X-ray diffraction.

PMID- 21069238
TI  - Enantioselective Friedel-Crafts alkylation of indole derivatives catalyzed by new
      Yb(OTf)3-pyridylalkylamine complexes as chiral Lewis acids.
AB  - New Yb(OTf)(3)-pyridylalkylamine complexes have been employed as chiral Lewis
      acids in the enantioselective Friedel-Crafts alkylation of indole derivatives
      with trifluoropyruvates. The influence of the substituents as well as the
      configuration of the ligands have been studied and allowed us to reach
      enantiomeric excesses up to 83%.

PMID- 21069239
TI  - Diameter-dependent, progressive alkylcarboxylation of single-walled carbon
      nanotubes.
AB  - We demonstrate diameter-dependent, progressive alkylcarboxylation of single
      walled carbon nanotubes by recycling a modified Billups-Birch reaction. The
      strong diameter dependence was confirmed by Raman spectroscopy.
      Alkylcarboxylation made SWNTs soluble in water, allowing the more readily
      functionalized, smaller diameter nanotubes to be enriched by water extraction.

PMID- 21069240
TI  - Highly efficient orange electrophosphorescence from a trifunctional organoboron
      Pt(II) complex.
AB  - High efficiency orange OLEDs have been achieved using a trifunctional Pt(II)
      complex that contains an electron-transporting triarylborane and a hole
      transporting triarylamine.

PMID- 21069241
TI  - Pentacobalt(II) cluster based pcu network exhibits both magnetic slow-relaxation
      and hysteresis behaviour.
AB  - A pentacobalt(II) cluster based 3D pcu network, [Co(5)(MU(3)
      OH)(2)(bpdc)(4)(dabco)(H(2)O)(2)] (bpdc = benzophenone-2,4'-dicarboxylate and
      dabco = 1,4-diazabicyclo[2,2,2] octane), exhibiting both slow magnetic relaxation
      and hysteresis behavior, has been hydrothermally synthesized.

PMID- 21069242
TI  - 10th anniversary issue: Japan.

PMID- 21069243
TI  - Synthesis and linear and nonlinear optical properties of metal-terminated
      bis(dioxaborine) polymethines.
AB  - Rh(III) and Ir(III) can be complexed to bipyridine groups attached to the termini
      of bis(dioxaborine)-capped heptamethines; these chromophores exhibit large third
      order polarisabilities at 1.55 MUm, while retaining good film-forming properties
      and linear optical transparency in the near infrared.

PMID- 21069244
TI  - Angular scattering using parameterized S matrix elements for the H + D2(v(i) = 0,
      j(i) = 0) -> HD(v(f) = 3, j(f) = 0) + D reaction: an example of Heisenberg's S
      matrix programme.
AB  - A neglected topic in the theory of reactive scattering is the use of
      parameterized scattering (S) matrix elements to calculate differential cross
      sections (DCSs). We construct four simple parameterizations, whose moduli are
      smooth step-functions and whose phases are quadratic functions of the total
      angular momentum quantum number. Application is made to forward glory scattering
      in the DCS of the H + D(2)(v(i) = 0, j(i) = 0) -> HD(v(f) = 3, j(f) = 0) + D
      reaction at a translational energy of 1.81 eV, where v and j are vibrational and
      rotational quantum numbers respectively. The parameterized S matrix elements can
      reproduce the forward scattering for centre-of-mass reactive scattering angles up
      to 30 degrees  and can identify the total angular momenta (equivalently, impact
      parameters) that contribute to the glory. The theoretical techniques employed to
      analyze structure in the DCS include: nearside-farside theory, local angular
      momentum theory--in both cases incorporating resummations of the partial wave
      series representation of the scattering amplitude--and the uniform semiclassical
      theory of forward glory scattering. Our approach is an example of Heisenberg's S
      matrix programme, in which no potential energy surface is used. Our calculations
      for the DCS using the four parameterized S matrix elements are counterexamples to
      the following universal statements often found in the chemical physics
      literature: "every molecular scattering investigation needs detailed information
      about the interaction potential," and "an accurate potential energy surface is an
      essential element in carrying out simulations of a chemical reaction". Both these
      statements are false.

PMID- 21069245
TI  - Methionine ligand selectively promotes monofunctional adducts between trans-EE
      platinum anticancer drug and guanine DNA base.
AB  - A detailed study on the reaction mechanism of trans-EE and trans-EE/Met Pt
      containing anticancer drugs was carried out in order to rationalize the
      experimental kinetic data concerning the whole process leading to DNA
      platination.

PMID- 21069246
TI  - Cobalt carbaporphyrin-catalyzed cyclopropanation.
AB  - Cobalt complexes of N-confused porphyrins and benziphthalocyanine, which both
      feature organometallic bonds at the macrocycle cores, catalyze the
      cyclopropanation of styrene with a higher trans-selectivity than the
      corresponding porphyrin and phthalocyanine complexes.

PMID- 21069247
TI  - Evaluation of four mathematical models to describe dissipation kinetics of 4-n
      nonylphenol and bisphenol-A in groundwater-aquifer material slurry.
AB  - The performance of four mathematical models (hockey stick, biexponential, first
      order double exponential decay, and first-order two-compartment) was evaluated to
      describe the dissipation kinetics for 4-n-nonylphenol (4-n-NP) and bisphenol-A
      (BPA) in groundwater-aquifer material slurry under aerobic and anaerobic
      conditions conducted under controlled laboratory conditions. The fit of each
      model to the measured values under both conditions was tested using an array of
      statistical indices to judge the model's ability to fit the measured datasets.
      Corresponding 50% (DT(50)) and 90% (DT(90)) dissipation values for each compound
      were numerically obtained and compared against each model. The model derived
      DT(50) values in groundwater-aquifer material ranged from 1.06 to 1.24 (4-n-NP)
      and 0.341 to 0.568 days (BPA) under aerobic condition, while they were 2- to 4
      fold higher under anoxic condition. DT(90) values for 4-n-NP ranged anywhere
      between 2.3 and 4.45 days under both conditions, while DT(90) values for BPA
      ranged from around 1 day to as high as 12 days under both conditions tested. A
      visual examination of the measured and fitted plots as well as the statistical
      indices showed that, with the exception of the hockey stick model, the models
      performed satisfactorily. Despite having only 3 parameters, the biexponential
      model could describe the dissipation kinetics very well and this was supported by
      the statistical indices generated for each case.

PMID- 21069249
TI  - Highly dispersed ultrafine Pt and PtRu nanoparticles on graphene: formation
      mechanism and electrocatalytic activity.
AB  - We demonstrate a robust strategy for obtaining a high dispersion of ultrafine Pt
      and PtRu nanoparticles on graphene by exploiting the nucleation of a metal
      precursor phase on graphite oxide surfaces. Our method opens up new possibilities
      to engineer graphene-based hybrids for applications in multifunctional nanoscale
      devices.

PMID- 21069248
TI  - Cytotoxicity of sophorolipid-gellan gum-gold nanoparticle conjugates and their
      doxorubicin loaded derivatives towards human glioma and human glioma stem cell
      lines.
AB  - Biocompatible gold nanoparticles were synthesized by using a naturally occurring
      gum--Gellan Gum--as a capping and reducing agent. These were further conjugated
      with sophorolipids which again were accessed through a biochemical transformation
      of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum
      reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN
      229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly
      even the simple sophorolipid-conjugated gellan gum reduced/capped gold
      nanoparticles showed greater efficacy in killing the glioma cell lines and,
      gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more
      prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated
      to these gold nanoparticles.

PMID- 21069250
TI  - Prevalence of intestinal parasitoses in children at the Xingu Indian Reservation.
AB  - OBJECTIVE: To evaluate the prevalence of intestinal parasitoses in Native
      Brazilian children from 2 to 9 years old. METHODS: A search for ova and parasites
      was conducted in the stools of children between 2 to 9 years old living in six
      indigenous villages located in the Middle and Lower Xingu River, to wit: Pavuru,
      Moygu, Tuiarare, Diauarum, Capivara, and Ngojwere. The study utilized the
      Paratest kit(r) (Diagnostek, Brazil) to preserve collected stools. Fecal samples
      were shipped to the Laboratory of the Pediatric Gastroenterology Division of the
      UNIFESP/EPM, in Sao Paulo, for analysis. The search for ova and parasites was
      performed utilizing the Hoffman method, and later through optical microscopic
      evaluation. Fecal samples were collected one year apart from each other. RESULTS:
      There were no significant statistical differences between the mean ages of the
      children from the six indigenous villages studied. The search for ova and
      parasites found positive results for the stools of 97.5% (198/202) and 96.1%
      (98/102) of children in the first and second collections, respectively. There was
      no statistical association with the children's age. The search performed one year
      later found no differences in the proportion of parasites identified in the first
      collection for protozoa (93.3% in 2007 versus 93.3% in 2008, McNemar = 0.01, p =
      0.1) or for helminths (37.1% in 2007 versus 38.2% in 2008, McNemar = 0.03, p =
      0.85). There were significant differences in prevalence of Entamoeba coli between
      2007 (43.8%) and 2008 (61.8%) (McNemar Chi 6.1; p = 0.0135). There were no
      significant differences for other parasites when comparing the results of the two
      studies. CONCLUSION: The high prevalence of intestinal parasitosis matched the
      elevated rates of environmental contamination in this indigenous community.

PMID- 21069251
TI  - Pediatric neurotoxocariasis with concomitant cerebral, cerebellar, and peripheral
      nervous system involvement: case report and review of the literature.
AB  - OBJECTIVE: To alert pediatricians to the neurologic consequences of toxocariasis
      and to describe the first pediatric case of neurotoxocariasis with concomitant
      cerebral, cerebellar and peripheral nervous system involvement. DESCRIPTION: We
      report a case of neurotoxocariasis in a previously healthy 5-year-old boy with
      unusual symptoms and multi-site involvement of both the central and peripheral
      nervous system. Differential diagnoses are discussed and the relevant literature
      is reviewed. Since the early 1950s, fewer than fifty cases have been described,
      mostly in adult patients. COMMENTS: Although human toxocariasis is one of the
      most common zoonotic helminth infections, neurotoxocariasis is a rare condition,
      especially in pediatric patients. Although toxocariasis usually presents as a
      self-limiting disease with no central nervous system involvement, when it does
      occur, it can be devastating. Neurotoxocariasis should be added to the
      differential diagnosis of pediatric patients with unusual neurologic symptoms
      accompanied by high levels of eosinophils in the cerebrospinal fluid. Early
      diagnosis and treatment can prevent long-term neurologic sequelae.

PMID- 21069252
TI  - Clinical, radiographic and hematological characteristics of Mycoplasma pneumoniae
      pneumonia.
AB  - OBJECTIVE: To describe the clinical, hematological and radiographic
      characteristics of children hospitalized for Mycoplasma pneumoniae pneumonia.
      METHOD: The study population consisted of 190 children between 3 months and 16
      years old, hospitalized for radiographically confirmed pneumonia. Patients were
      divided into two groups, to wit: 95 children with Mycoplasma pneumoniae
      pneumonia, as diagnosed using the enzyme-linked immunosorbent assay (ELISA)
      method; and 95 children with pneumonia caused by other etiologic agents. Using a
      validated scoring system, the clinical, hematological and radiographic findings
      of both groups were compared to differentiate Mycoplasma pneumoniae pneumonia
      (group 1) from pneumonia caused by other etiologic agents (group 2), itself
      divided into two groups, bacterial (n = 75) and viral (n = 20). RESULTS:
      Mycoplasma pneumoniae pneumonia was found most often in girls (p < 0.01), older
      children (p < 0.01), and patients with dry cough (p < 0.01) and extrapulmonary
      manifestations (p < 0.01). The clinical, hematological and radiographic variables
      of Mycoplasma pneumoniae pneumonia (mean score = 6.95) scored between those found
      in bacterial (mean score = 8.27) and viral pneumonia (mean score = 0.90).
      CONCLUSION: Results suggest that the scoring system can contribute to the
      presumptive diagnosis of Mycoplasma pneumoniae pneumonia and help differentiate
      pneumonic status caused by other etiologic agents.

PMID- 21069253
TI  - Different domains of health functioning as predictors of sickness absence--a
      prospective cohort study.
AB  - OBJECTIVES: The aim of this study was to examine different domains of health
      functioning as predictors of sickness absence. METHODS: The Short Form 36 (SF-36)
      is one of the best known instruments measuring various domains of physical and
      mental health functioning. A questionnaire including the SF-36 was mailed to 40
      60-year-old employees of the City of Helsinki in 2000-2002. For the subsequent
      three years, sickness absence episodes >2 weeks were derived from the employer's
      register. The predictive ability of the eight subscales and two component
      summaries of the SF-36 were compared using regression methods and receiver
      operating characteristic (ROC) curve analysis. RESULTS: All eight SF-36 subscales
      and the two component summaries predicted the occurrence of sickness absence over
      the follow-up period. Among women, bodily pain was the strongest predictor, with
      1 standard deviation increase in bodily pain increasing the occurrence of
      sickness absence by 77% [95% confidence interval (95% CI) 68-86%]. Role
      limitations due to emotional problems were the weakest predictor of sickness
      absence (29%, 95% CI 23-36%). Among men, the results were similar to those of
      women. In both genders, the area under the ROC curve was largest for bodily pain,
      general health, and physical functioning and lowest for mental health and role
      limitation due to emotional problems. CONCLUSIONS: The subscales measuring
      physical domains of functioning were more strongly associated with sickness
      absence than the mental subscales. In particular, ability to perform daily
      activities, pain, and general health were important predictors of sickness
      absence >2 weeks.

PMID- 21069254
TI  - Protective effects of Curcuma longa against cerulein-induced acute pancreatitis
      and pancreatitis-associated lung injury.
AB  - Curcuma longa (CL) has been reported to possess a variety of pharmacological
      activities. However, the effects of CL on acute pancreatitis (AP) have not yet
      been determined. To this end, we examined the effects of CL on cerulein-induced
      AP. Cell viability and cytokine productions were measured in pancreatic acini.
      Mice were divided into 3 groups: i) Normal group, ii) normal saline-treated
      group, iii) group treated with CL at a dose of 0.05, 0.1, 0.5 and 1 g/kg. CL was
      administered orally to mice for 7 days. The mice were intraperitoneally injected
      with the stable cholecystokinin analogue, cerulein (50 MUg/kg), every hour for a
      total of 6 h. The mice were sacrificed 6 h after the completion of the cerulein
      injections. Blood samples were obtained to determine serum amylase, lipase and
      cytokine levels. The pancreas was rapidly removed for morphological examination,
      measurement of tissue myeloperoxidase activity, as well as the level of cytokines
      and heme oxygenase-1 (HO-1). The CL treatment reduced cerulein-induced cell death
      and cytokine production in pancreatic acini. The administration of CL
      significantly ameliorated the severity of pancreatitis and pancreatitis
      associated lung injury, as was shown by the reduction in pancreatic edema,
      neutrophil infiltration, vacuolization, necrosis, serum amylase, lipase and
      cytokine levels, and mRNA expression of multiple inflammatory mediators such as
      interleukin (IL)-1beta and -6 and tumor necrosis factor (TNF)-alpha. In order to
      identify the regulatory mechanism of CL on cerulein-induced pancreatitis, we
      examined the level of HO-1 in the pancreas. We found that the administration of
      CL induced HO-1. Our results suggest that CL plays a protective role in the
      development of AP and pancreatitis-associated lung injury.

PMID- 21069255
TI  - In vitro study of inhibitory millimeter wave treatment effects on the TNF-alpha
      induced NF-kappaB signal transduction pathway.
AB  - Abnormal activation of the nuclear factor-kappaB (NF-kappaB) in chondrocytes
      initiates the transcription of inflammatory mediators, promotes their generation
      and release, and amplifies initial inflammatory signals. This results in the
      release of chondral matrix-degrading enzymes and accelerates the degeneration of
      articular cartilage. As a non-pharmaceutical and non-invasive physical therapy
      regimen, millimeter wave treatment has been successfully used for the treatment
      of osteoarthritis. In this study, chondrocytes were derived from the cartilages
      of knee joints of 4-week-old male Sprague-Dawley rats and were mechanically
      digested by collagenase type II treatment for further culture in vitro. The third
      passage chondrocytes were stained with toluidine blue and treated with a gradient
      of tumor necrosis factor-alpha (TNF-alpha) for various times. Chondrocytic
      activity was measured by MTT assay, and the apoptotic rate of the chondrocytes
      was determined with Hocehst 33342 staining to identify effective treatment
      concentrations and durations and to establish an apoptosis model for the
      chondrocytes in response to TNF-alpha. Using this model, the chondrocytes were
      randomly divided to receive millimeter wave treatment for various times. The
      apoptotic rate of the chondrocytes was measured by Annexin V-FITC staining and
      the protein expression levels of RIP, TAK1, IkappaB kinase (IKK)-beta, IkappaB
      alpha and NF-kappaB, were determined by Western blotting. Chondrocytic structure
      was examined by transmission electronic microscopy. The apoptotic rates were
      significantly lower at 4 and 8 h of treatment than at 0 and 2 h. The expression
      levels of RIP, TAK1, IKK-beta and NF-kappaB were also significantly lower at 4
      and 8 h than at 0 and 2 h, whereas that of IkappaB-alpha was significantly higher
      at 4 and 8 h than at 0 and 2 h. Therefore, we can conclude that millimeter wave
      treatment can inhibit the activation of the TNF-alpha-mediated NF-kappaB signal
      transduction pathway through the down-regulation of RIP, TAK1, IKK-beta and NF
      kappaB, and the up-regulation of IkB-alpha, in chondrocytes.

PMID- 21069256
TI  - Influence of LPS, TNF, TGF-beta1 and IL-4 on the expression of MMPs, TIMPs and
      selected cytokines in rat synovial membranes incubated in vitro.
AB  - Synovial membranes are formed by four main types of cells, i.e. fibroblasts,
      macrophages, epitheliocytes and adipocytes. To study the combined effect of
      various factors on these cell populations, synovial membranes dissected from rat
      knee joints were incubated in control medium or medium with lipopolysaccharide
      (LPS), TNF, TGF-beta1 or IL-4 for 12 h. LPS stimulated TNF secretion and both
      agents stimulated secretion of IL-6. TGF-beta1 slightly increased IL-6 secretion.
      LPS increased the mRNA levels of IL-6, IL-1beta, TGF-beta1, MMP1a, MMP1b, MMP3,
      MMP9, MMP13, MMP14, TIMP1 and TIMP3 while the mRNA levels of MMP2, TIMP2 and
      TIMP4 were significantly decreased. Expression of IL-1beta, MMP1a, MMP1b, MMP3,
      MMP9, MMP13 and TIMP1 increased after TNF treatment, while mRNA levels of MMP2,
      MMP14, TIMP2, TIMP3 and TIMP4 were decreased. TGF-beta1 decreased the mRNA levels
      of IL-1beta, all MMPs, TIMP1, TIMP2, TIMP4 and increased mRNA levels of itself
      and TIMP3. IL-4 decreased mRNA levels of IL-1beta, TGF-beta1, MMP2, MMP9, MMP13
      and all TIMPs. Only LPS decreased the amount and activity of MMP2. The effect of
      LPS and cytokines on most of the MMPs and TIMPs produced by whole synovial
      membrane was in good agreement with previous studies on their action on similar
      types of cells as those present in synovial membranes, but originating from other
      tissues. All tested agents decreased MMP2 mRNA expression levels and in the case
      of LPS also the protein level and its activity determined by zymography, contrary
      to previous observations on isolated cell populations. This indicates that the
      response of the organized tissue is an interplay of all components and cannot be
      deduced from the individual reactions.

PMID- 21069257
TI  - The cohesin-interacting protein, precocious dissociation of sisters 5A/sister
      chromatid cohesion protein 112, is up-regulated in human astrocytic tumors.
AB  - Glioblastoma multiforme (GBM) is the most prevalent, highly malignant, invasive
      and difficult-to-treat primary brain tumor in adults. At the genetic level, it is
      characterized by a high degree of chromosomal instability and aneuploidy. It has
      been shown that defects in the mitotic spindle checkpoint could lead to the
      development of aneuploidy as well as tumorigenesis. Additional proteins
      regulating sister chromatid cohesion could also be involved in maintaining the
      fidelity of chromosome segregation. One such protein is the precocious
      dissociation of sisters 5A (Pds5A), also known as sister chromatid cohesion
      protein 112. It is a nuclear protein, expressed from the S right through to the
      mitotic phase. It is highly conserved from yeast to man and plays a role in the
      establishment, maintenance and dissolution of sister chromatid cohesion. The
      mutation of Pds5A orthologs in lower organisms results in chromosome
      missegregation, aneuploidy and DNA repair defects. It is considered that such
      defects can cause either cell death or contribute to the development of cancer
      cells. Indeed, altered expression levels of Pds5A have been observed in tumors of
      the breast, kidney, oesophagus, stomach, liver and colon. Malignant gliomas,
      however, have not been analysed so far. Herein, we report on the cloning of
      Rattus norvegicus Pds5A and on the analysis of its expression pattern in rat
      tissue. We also show that Pds5A is significantly overexpressed at both the mRNA
      and protein level and that this overexpression correlates positively with the WHO
      grade of human gliomas. However, functional assays show that the siRNA-mediated
      knockdown of Pds5A affects sister chromatid cohesion but does not influence
      mitotic checkpoint function or the proliferation and survival of GBM cells.
      Although the mechanism by which Pds5A functions in GBM cells remains unclear, its
      overexpression in high grade gliomas implies that it could play a pivotal role
      during the development and progression of astrocytic tumors.

PMID- 21069258
TI  - Inhibitory effect of curcumin on angiogenesis in ectopic endometrium of rats with
      experimental endometriosis.
AB  - The aim of this study was to observe the inhibitory effect of curcumin on
      endometriosis (EMS) and to determine its influence on vascular endothelial growth
      factor (VEGF) and microvessel density (MVD) in eutopic and ectopic endometrium of
      experimental rats, thus exploring the pathogenesis of EMS offering more
      experimental evidence for the clinical use of curcumin. Forty-eight female virgin
      rats were subjected to autotransplantation of endometrium during the estrus
      stage. After four weeks, 8 rats were randomly sacrificed to confirm that the rat
      model was successful. The remaining rats were randomly divided into four groups.
      Three groups were intragastrically administered curcumin (50, 100 and 150 mg/kg),
      and the model group was intragastrically administered vehicle alone. All rats
      were treated daily for four continuous weeks and examined by histology and
      immunohistochemical staining for MVD of eutopic and ectopic endometrium. Our
      results revealed that the cubic capacity of focal tissue in gross appearance was
      high in the model group and dose-dependently diminished after treatment with
      curcumin (P<0.05). There was an increase in MVD and VEGF in the ectopic
      endometrium, which was decreased significantly after treatment with curcumin
      (P<0.05); the effects being dose-dependent. The correlation between MVD and VEGF
      was positive. In conclusion, heterogeneity was found to exist between eutopic and
      ectopic endometrium due to differences noted in MVD and the expression of VEGF
      between the eutopic and ectopic endometrium in the model group. Curcumin
      decreased the quantity of microvessels and VEGF protein expression in the
      heterotopic endometrium of rats with EMS.

PMID- 21069259
TI  - NCO-sP(EO-stat-PO) surface coatings preserve biochemical properties of RGD
      peptides.
AB  - We have previously reported that star shaped poly(ethylene oxide-stat-propylene
      oxide) macromers with 80% EO content and isocyanate functional groups at the
      distal ends [NCO-sP(EO-stat-PO)] can be used to generate coatings that are non
      adhesive but easily functionalized for specific cell adhesion. In the present
      study, we investigated whether the NCO-sP(EO-stat-PO) surfaces maintain peptide
      configuration-specific cell-surface interactions or if differences between
      dissimilar binding molecules are concealed by the coating. To this end, we have
      covalently immobilized both linear-RGD peptides (gRGDsc) and cyclic-RGD (RGDfK)
      peptides in such coatings. Subsequently, SaOS-2 or human multipotent mesenchymal
      stromal cells (MSC) were seeded on these substrates. Cell adhesion, spreading and
      survival was observed for up to 30 days. The time span for cell adherence was not
      different on linear and cyclic RGD peptides, but was shorter in comparison to the
      unmodified glass surface. MSC proliferation on cyclic RGDfK modified coatings was
      4 times higher than on films functionalized by linear gRGDsc sequences,
      underlining that the NCO-sP(EO-stat-PO) film preserves the configuration-specific
      biochemical peptide properties. Under basal conditions, MSC expressed osteogenic
      marker genes after 14 days on cyclic RGD peptides, but not on linear RGD peptides
      or the unmodified glass surfaces. Our results indicate specific effects of these
      adhesion peptides on MSC biology and show that this coating system is useful for
      selective testing of cellular interactions with adhesive ligands.

PMID- 21069260
TI  - Evaluation of the effect of flavangenol on serum lipid peroxide levels and
      development of atherosclerosis in spontaneously hyperlipidemic B6.KOR-Apoeshl
      mice.
AB  - Antioxidative flavonoids are used to reduce the risk of cardiovascular diseases
      in humans. However, the precise mechanism for the anti-atherosclerotic actions of
      flavonoids remains to be elucidated. In the present study, to assess the
      mechanism for the action of antioxidative flavonoids on atherosclerosis, we
      investigated the effect of flavangenol, one of the most potent antioxidants
      currently known, on spontaneously hyperlipidemic B6.KOR-Apoeshl mice. Flavangenol
      was orally administered to B6.KOR-Apoeshl mice ad libitum (6 mg
      flavangenol/mouse/day). After 6 months, serum levels of lipids (total
      cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) and lipid
      peroxide were measured, and histopathological changes (lipid accumulation and
      inflammatory cell infiltration) in the aortic root were evaluated. Serum levels
      of total cholesterol and LDL-cholesterol were markedly increased, and HDL
      cholesterol levels were decreased in B6.KOR-Apoeshl mice compared to C57BL/6 mice
      used as a control (p<0.001). Among these serum lipids, only HDL-cholesterol
      levels were significantly increased by flavangenol administration (p<0.05).
      Moreover, Oil Red O staining (lipid accumulation) was significantly increased in
      B6.KOR-Apoeshl mice compared to C57BL/6 mice (p<0.001). Notably, flavangenol
      administration significantly suppressed the increase in Oil Red O staining
      (p<0.01). Similarly, inflammatory cell infiltration into the intima was
      significantly increased in B6.KOR-Apoeshl mice compared to C57BL/6 mice (p<0.01),
      and flavangenol administration significantly suppressed the inflammatory cell
      infiltration (p<0.01). Importantly, flavangenol administration significantly
      reduced the increase of serum lipid peroxide levels in B6.KOR-Apoeshl mice
      (p<0.05). Together, these observations indicate that flavangenol, one of the most
      potent antioxidants, exerts its anti-atherosclerotic action on spontaneously
      hyperlipidemic and atherosclerotic B6.KOR-Apoeshl mice, possibly by increasing
      HDL-cholesterol levels and reducing lipid peroxide levels, thereby suppressing
      the lipid accumulation (formation of atherosclerotic lesions) and inflammatory
      cell infiltration (chronic inflammation) in the intima of the aortic root.

PMID- 21069261
TI  - Experimental study of low-frequency electroacupuncture-induced differentiation of
      bone marrow mesenchymal stem cells into chondrocytes.
AB  - In the present study, we investigated the effect of low-frequency
      electroacupuncture (EA) on the differentiation of bone mesenchymal stem cells
      (BMSCs) into chondrocytes and the molecular mechanism involved. We isolated BMSCs
      from Sprague-Dawley (SD) rat bone marrow. Third-generation SD rat BMSCs (P3
      BMSCs) were harvested and characterized by flow cytometry with FITC staining.
      Data indicated that the positive rates of CD90 and CD45 were 98.22 and 1.91%,
      respectively, indicating the high purity of the BMSCs. The P3 BMSCs were treated
      with EA for 15 or 30 min daily for 7 or 14 days. Using optical microscopy and
      transmission electron microscopy, we found that EA induced morphological changes
      in the BMSCs, displaying typical morphology of early chondrocytes. In addition,
      we found that the cytoplasm and extracellular matrices were metachromatically
      stained by toluidine blue in the treated cells in a dose-dependent manner,
      indicating that EA treatment resulted in the expression of glycosaminoglycan.
      Furthermore, upon immunohistocytochemical staining and Western blotting, we found
      that EA treatment significantly and dose-dependently induced expression of
      chondrocyte-specific matrix protein type II collagen, which may have been
      mediated by the transcription factor Sox9, as the mRNA expression of Sox9 was
      found to be significantly increased after EA treatment. Taken together, these
      results suggest that EA can be employed as a novel non-drug-inducing method for
      the differentiation of BMSCs into chondrocytes.

PMID- 21069262
TI  - Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post
      mortem investigations.
AB  - The present report concerns several post-mortem variables examined in sand rats
      that were either maintained on a vegetal diet (control animals) or exposed first
      during a 20-day transition period to a mixed diet consisting of a fixed amount of
      a hypercaloric food and decreasing amounts of the vegetal food and then to a 30
      day experimental period of exposure to the hypercaloric food. During the latter
      period, all animals were either given free access to food or fasting daily for 15
      h, i.e. from 5.00 p.m. to 8.00 a.m. The body weight, liver wet weight, pancreas
      wet weight, plasma glucose and haemoglobin A1c concentration, plasma insulin
      concentration, insulinogenic index, insulin resistance HOMA, plasma cholesterol
      and triglyceride concentration, liver triglyceride and phospholipid content were
      all measured. Pancreatic islet (insulin, GLUT2) and liver (lipid droplets)
      histology were also examined. The main findings consisted in a lower body weight
      of fasting than non-fasting animals, a higher liver weight in non-diabetic and
      diabetic rats than in control non-fasting (but not so in fasting) animals, a
      decrease of pancreas weight in non-diabetic and diabetic as distinct from control
      animals, a fasting-induced decrease in plasma glucose, plasma insulin and insulin
      resistance HOMA, plasma cholesterol and triglyceride concentration and
      triglyceride liver content.

PMID- 21069264
TI  - Popeye domain-containing 1 is down-regulated in failing human hearts.
AB  - Congestive heart failure, a complex disease of heterogeneous etiology, involves
      alterations in the expression of multiple genes. The Popeye domain-containing
      (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is
      evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been
      shown to play an important role in skeletal and cardiac muscles subjected to
      injury or stress. However, it has never been explored in human hearts. In
      biopsies from non-failing and failing human hearts, we examined the cellular
      distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs.
      POPDC1 was visualized by immunohistochemistry and estimated by Western
      immunoblotting. The mRNA levels of POPDC1-3 and beta myosin heavy chain (MYHC7)
      were assessed using reverse transcription/quantitative polymerase chain reaction.
      POPDC1 was predominantly localized in the sarcolemma with an enhanced expression
      in the intercalated discs. In failing hearts, many cardiomyocytes appeared
      deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed
      in the four heart chambers with higher transcript levels in the ventricles
      compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA
      and protein in the left ventricle. Correlation analyses of mRNA levels among the
      failing heart specimens indicated the coordinated regulation of POPDC1 with
      POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression
      is modified in end-stage heart failure in humans in a manner suggesting
      regulatory and/or functional differences between the three family members and
      that POPDC1 is particularly susceptible to this condition.

PMID- 21069263
TI  - Nuclear magnetic resonance in conjunction with functional genomics suggests
      mitochondrial dysfunction in a murine model of cancer cachexia.
AB  - Cancer patients commonly suffer from cachexia, a syndrome in which tumors induce
      metabolic changes in the host that lead to massive loss in skeletal muscle mass.
      Using a preclinical mouse model of cancer cachexia, we tested the hypothesis that
      tumor inoculation causes a reduction in ATP synthesis and genome-wide aberrant
      expression in skeletal muscle. Mice implanted with Lewis lung carcinomas were
      examined by in vivo 31P nuclear magnetic resonance (NMR). We examined ATP
      synthesis rate and the expression of genes that play key-regulatory roles in
      skeletal muscle metabolism. Our in vivo NMR results showed reduced ATP synthesis
      rate in tumor-bearing (TB) mice relative to control (C) mice, and were cross
      validated with whole genome transcriptome data showing atypical expression levels
      of skeletal muscle regulatory genes such as peroxisomal proliferator activator
      receptor gamma coactivator 1 beta (PGC-1beta), a major regulator of mitochondrial
      biogenesis and, mitochondrial uncoupling protein 3 (UCP3). Aberrant pattern of
      gene expression was also associated with genes involved in inflammation and
      immune response, protein and lipid catabolism, mitochondrial biogenesis and
      uncoupling, and inadequate oxidative stress defenses, and these effects led to
      cachexia. Our findings suggest that reduced ATP synthesis is linked to
      mitochondrial dysfunction, ultimately leading to skeletal muscle wasting and thus
      advance our understanding of skeletal muscle dysfunction suffered by cancer
      patients. This study represents a new line of research that can support the
      development of novel therapeutics in the molecular medicine of skeletal muscle
      wasting. Such therapeutics would have wide-spread applications not only for
      cancer patients, but also for many individuals suffering from other chronic or
      endstage diseases that exhibit muscle wasting, a condition for which only
      marginally effective treatments are currently available.

PMID- 21069265
TI  - Suppression of Idol expression is an additional mechanism underlying statin
      induced up-regulation of hepatic LDL receptor expression.
AB  - Recent studies have identified proprotein convertase subtilisin/kexin type 9
      (PCSK9) and Idol as negative regulators of low density lipoprotein receptor
      (LDLR) protein stability. While the induction of PCSK9 transcription has been
      recognized as a limitation to the statin cholesterol-lowering efficacy at higher
      doses, it is unknown whether Idol is involved in the statin-mediated up
      regulation of the hepatic LDLR. Here we report that statins exert opposite
      effects on PCSK9 and Idol gene expression in human hepatoma-derived cell lines
      and primary hepatocytes isolated from hamsters and rats. While PCSK9 expression
      was induced, the level of Idol mRNA rapidly declined in statin-treated cells in a
      dose-dependent manner. This differs from the effect of the liver X receptor
      ligand, GW3965, which increased the expression of both PCSK9 and Idol. We further
      show that cellular depletion of Idol by siRNA transfection did not change PCSK9
      expression levels in control and statin-treated cells; however, the basal level
      of LDLR protein increased by 60% in Idol siRNA transfected HepG2 cells. More
      importantly, the increase in LDLR protein abundance by rosuvastatin and
      atorvastatin treatment was compromised by Idol siRNA transfection. Collectively,
      our present findings suggest that the suppression of Idol gene expression in
      liver cells is an additional mechanism underlying the statin-induced up
      regulation of hepatic LDLR expression. This may contribute to the
      hypocholesterolemic effects of statins observed in clinical settings.

PMID- 21069266
TI  - The Wnt5a/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in
      K562 cells.
AB  - Wnt5a has been shown to be involved in cancer progression in a variety of tumor
      types, and regulates multiple intracellular signaling cascades; it is a
      representative ligand that activates a noncanonical Wnt signaling pathway. The
      mechanism governing how Wnt5a determines the specificity of these pathways and
      the relationship with tumorigenesis is still unknown. In this study, we aimed to
      clarify the tumor suppressor role of Wnt5a in leukemogenesis. In particular, we
      focused on Ror2 functioning as a Wnt5a receptor to mediate noncanonical Wnt
      signaling, which inhibits canonical Wnt signaling in K562 cells. We found that up
      regulation of Wnt5a expression increased Ror2 expression in K562 cells and Wnt5a
      and Ror2 were co-expressed in the cytoplasm. Also, Wnt5a induced the
      intrnalization of Ror2. Co-immunoprecipitation experiments were performed to
      determine whether Ror2 binds to Wnt5a, and inhibits Wnt5a binding with Frizzled4
      and LRP5 in Wnt5a treated K562 cells. Wnt5a had no effect on total beta-catenin
      expression levels, but regulated tyrosine phosphorylation of beta-catenin and
      translocation of beta-catenin from the cytoplasm to the nucleus. Furthermore,
      expression of Wnt5a was associated with suppression of beta-catenin/TCF-dependent
      transcriptional activity and down-regulated the expression of cyclin D1, a
      downstream target gene of the canonical Wnt signaling pathway. We hypothesize
      that Wnt5a plays the role of a tumor suppressor in leukemogenesis through the
      Wnt5a/Ror2 noncanonical signaling pathway that inhibits Wnt canonical signaling.

PMID- 21069267
TI  - Combination of ionising irradiation and hyperthermia activates programmed
      apoptotic and necrotic cell death pathways in human colorectal carcinoma cells.
AB  - PURPOSE: The malignancy of tumor cells can be attenuated by interfering with cell
      death pathways. Since hyperthermia (HT) is a very potent radiosensitizer, the
      influence of HT (41.5  degrees C for 1 hour) alone and in combination with
      ionising irradiation (X-ray; 5 Gy or 10 Gy) on the form of cell death as well as
      on the expression of proteins known to be major components in tumor cells'
      apoptotic and necrotic pathways were examined in colorectal tumor cells. MATERIAL
      AND METHODS: The expression of proteins was analysed by western blot and the
      relative activity of caspases-3/7 by fluorescence- based assay. Colony formation
      was analysed using the clonogenic assay and cell death was determined with
      annexin V-FITC/propidium iodide staining. RESULTS: Combining X-ray with HT led to
      similar activation of caspase-3/7 and p53 expression in comparison to irradiation
      only while the amount of the pro-apoptotic proteins PUMA and Bax was increased in
      HCT15 and SW480 cells. HT alone or combinations with X-ray further resulted in a
      temporarily increased level of the anti-apoptotic protein Bcl-2. Irradiation plus
      HT further led to an up-regulation of IRF-5. The levels of RIP-1, a marker for
      programmed necrosis, increased in tumor cells which were treated with HT and/or X
      ray. Combining 5 Gy irradiation with HT compared to irradiation resulted in a
      significantly increased number of necrotic tumor cells and in decreased colony
      formation. CONCLUSION: The combined treatment of colorectal tumor cells with X
      ray and HT activates distinct tumor cell pathways and fosters the early
      appearance of a necrotic tumor cell phenotype.

PMID- 21069268
TI  - Multidisciplinary approach in the treatment of T1 glottic cancer. The role of
      patient preference in a homogenous patient population.
AB  - BACKGROUND AND PURPOSE: To compare oncological outcome and voice quality among a
      uniform and well-defined subset of patients with T1 glottic carcinoma. PATIENTS
      AND METHODS: Patients, affected by laryngeal glottic carcinoma, treated by laser
      CO2 surgery or radiotherapy, have been analyzed. Overall survival and disease
      free survival were calculated. In order to verify differences in functional
      outcomes and voice quality, all patients were interviewed during their last
      follow-up visit during 2009 using the VHI (Voice Handicap Index) questionnaire.
      The data were analyzed using the MedCalc software. RESULTS: A total of 143
      patients were analyzed: 73 underwent surgery and 70 underwent radiotherapy. No
      statistically significant differences were found between the two groups in terms
      of overall survival and disease-free survival; dividing patients into stages T1a
      and T1b also made no difference. In order to evaluate the differences in outcomes
      for surgery and radiotherapy, patients were interviewed using the VHI
      questionnaire. Better scores for each category in the VHI were found for patients
      receiving radiotherapy compared to surgery (physical: p = 0.0023; functional: p <
      0.0001; environmental: p < 0.001). The median VHI score for radiotherapy patients
      was 4, while for surgical patients it was 18 (p < 0.0001). CONCLUSION: This study
      confirms the well-known knowledge that results from radiotherapy and surgery in
      early glottic cancer treatment are equivalent. Furthermore, the role of patient
      preference in the treatment modality choice and the value of a multidisciplinary
      approach for a detailed and multi-oriented discussion with the patient are
      outlined.

PMID- 21069269
TI  - Variability in bladder volumes of full bladders in definitive radiotherapy for
      cases of localized prostate cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate variation in bladder volume of full bladders
      in definitive radiotherapy for localized prostate cancer and to investigate
      potential predictors of increased bladder volume variations. PATIENTS AND
      METHODS: In 40 patients, the bladder volume was measured with megavoltage
      computed tomography (MVCT) imaging performed just before irradiation during the
      administration of the 1st fraction (#1), the 10th fraction (#10), the 20th
      fraction (#20), and the 30th fraction (#30). Patients were instructed to avoid
      urinating for 60-90 minutes before the planning CT (pln-CT) scan and before daily
      irradiation. Patients were also encouraged to drink an unspecified volume of
      liquid that would result in a clear but tolerable urge to urinate. RESULTS: The
      population-mean bladder volume (+/-1SD) was 219 ml (+/-83 ml) at the planning CT
      scan (pln-CT), 186 ml (+/-96 ml) at #1, 149 ml (+/-73 ml) at #10, 137 ml (+/-59
      ml) at #20, and 136 ml (+/-60 ml) at #30. The mean intrapatient variation in
      bladder volume (1 SD relative to the mean bladder volume of each patient) was 38%
      (range: 10-84%). The bladder volume at the pln-CT was correlated with the
      intrapatient variance in bladder volume with a correlation coefficient of 0.54
      and p <0.001. CONCLUSION: We observed a significant decline in bladder volumes
      during the course of radiotherapy. The bladder volume at the pln-CT was a
      significant predictor of increased bladder volume variations.

PMID- 21069270
TI  - Total body irradiation (TBI) in pediatric patients. A single-center experience
      after 30 years of low-dose rate irradiation.
AB  - PURPOSE: To retrospectively analyze patient characteristics, treatment, and
      treatment outcome of pediatric patients with hematologic diseases treated with
      total body irradiation (TBI) between 1978 and 2006. PATIENTS AND METHODS: 32
      pediatric patients were referred to the Department of Radiation-Oncology at the
      University of Zurich for TBI. Records of regular follow-up of 28 patients were
      available for review. Patient characteristics as well as treatment outcome
      regarding local control and overall survival were assessed. A total of 18
      patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2
      from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from
      anaplastic anemia. The cohort consisted of 15 patients referred after first
      remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2
      196 months) with 15 patients alive at the time of last follow-up. Eight patients
      died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2
      patients died of a secondary malignancy. RESULTS: The 5-year overall survival
      rate (OS) was 60%. Overall survival was significantly inferior in patients
      treated after relapse compared to those treated for newly diagnosed leukemia (24%
      versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for
      more than 36 months following TBI. Late effects (RTOG >= 3) were pneumonitis in 1
      patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe
      cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose)
      and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth
      disturbances were observed in all patients treated prepubertally. In 2 patients
      with identical twins treated at ages 2 and 7, a loss of 8% in final height of the
      treated twin was observed. CONCLUSION: As severe late sequelae after TBI, we
      observed 2 secondary malignancies in 11 patients who survived in excess of 36
      months. However, long-term morbidity is moderate following treatment with the
      fractionated TBI at the low-dose rate that was generally used here. Conditioning
      for bone marrow transplantation without radiation is an attractive option, but is
      not sufficiently effective to completely replace TBI for the most common
      pediatric indications.

PMID- 21069271
TI  - [Caspofungin after solid organ transplantation in Germany: observational study on
      treatment of invasive fungal infections].
AB  - BACKGROUND: This study was a pre-planned country-specific secondary analysis of
      results in Germany from a multinational multicenter observational study to
      retrospectively evaluate clinical outcomes with caspofungin in patients with
      probable and proven invasive fungal infection following solid organ
      transplantation (SOT). METHODS: Data were retrospectively collected on a single
      episode of invasive fungal infection (IFI) in patients who had a SOT between
      January 2004 and June 2007. Effectiveness was reported as the proportion of
      patients who received at least five doses of caspofungin with a favorable
      (complete or partial) response. Safety was assessed for patients who received at
      least one dose of caspofungin. Descriptive statistics were employed for all
      evaluations. RESULTS: A total of 41 SOT patients (27 male, 14 female; median age
      56 years, median APACHE II score at start of caspofungin therapy 23) were
      enrolled from 5 sites in Germany. Organs transplanted were mainly heart (51%) and
      liver (46%). Prevalent risk factors for IFI at baseline were use of central
      venous catheter (37 out of 41 patients, 90%), steroid use (37 out of 41 patients,
      90%), recent stay in intensive care (36 out of 41 patients, 88%),and duration of
      SOT procedure >5 hours (21 out of 41 patients, 51%). Candidiasis was diagnosed in
      34 patients (83%) and aspergillosis in 10 patients (24%). The lungs were the most
      common site of IFI (21 out of 41, 51%). Caspofungin as monotherapy was received
      by 28 patients (68%); 6 patients (15%) received caspofungin as salvage therapy
      for IFI, in most cases because they were refractory to prior antifungal drugs.
      Immunosuppressants were administered with caspofungin in 39 out of 41 patients
      (95%). In subjects with at least 5 doses of caspofungin (modified intention to
      treat population) the favorable response rate at the end of caspofungin therapy
      was 88% overall, 29 out of 33 patients; 95% confidence interval (95%-CI) 72-97%),
      86% (19 out of 22 patients) with monotherapy and 91% (10 out of 11 patients) with
      combination therapy. No (serious) adverse events or drug interactions related to
      treatment with caspofungin were reported. The overall survival rate was 79% (26
      out of 33 patients; 95%-CI 61-91%) at 7 days after completion of caspofungin
      treatment. CONCLUSION: Caspofungin was found to be an effective treatment of
      probable and proven invasive fungal infections in patients following SOT in
      Germany.

PMID- 21069272
TI  - [Disappearing borders between the disciplines vascular surgery and interventional
      radiology from the perspective of vascular surgeons].
AB  - Demographic development leads to an exponential increase of cardiovascular
      illness. Additionally, technical development of conservative and invasive
      treatment modalities adds to an increase of specified therapy. Both items lead to
      increased specialization and a new orientation of vascular specialties. This
      concept implies that specific contents are referred and contained to the partner
      specialties. Angiology, vascular surgery and radiology are primary partners in
      this concept, however, in the following article the focus lies on vascular
      surgery and radiology.

PMID- 21069273
TI  - [Acoustic neuroma (vestibular schwannoma) therapy from an oto-rhino
      laryngological perspective].
AB  - Acoustic neuroma/vestibular schwannoma treatment has changed considerably since
      the 1990s, when surgical treatment was recommended in all cases of schwannoma,
      whereas nowadays a more differentiated approach is taken. The three classical
      approaches (translabyrinthine, transtemporal, and suboccipital) still have their
      surgical value; however, greater importance is apportioned to radiotherapy
      (radiosurgery, gamma- and cyber-knife). Magnetic resonance imaging in particular
      has changed diagnostics and how tumor growth is followed. Electrophysiological
      monitoring of facial and auditory nerves has helped lower postoperative
      morbidity. New issues have been raised regarding quality of life.
      Neuropsychological investigations for cognitive and mnestic performance following
      procedures in the cerebellopontine angle have highlighted problem areas receiving
      hitherto little attention. Finally, the therapy of this benign lesion should be
      planned individually, taking the patient's age as well as their professional and
      personal status into consideration.

PMID- 21069275
TI  - [35-year old patient with severe thromboembolism].
AB  - We report a case of a 35 year old male with severe deep vein thrombosis of the
      lower limb on both sides and pulmonary embolism. A Klinefelter's mosaic (47,XXY
      [81%]/48,XXXY [19%]) was diagnosed. Because no other cause for this
      thromboembolism was found, we assume that in part, it was caused by the
      Klinefelter's mosaic. In all male patients presenting with thromboembolism,
      especially those with an unusual habitus, a Klinefelter's syndrome should be
      considered as differential diagnosis. Testosterone substitution therapy should be
      started in all patients with Klinefelter's syndrome to prevent further disease.

PMID- 21069274
TI  - [What has been confirmed in the treatment of inflammatory bowel disease?].
AB  - The therapy of inflammatory bowel diseases is currently guided by clinical
      variables. An escalation of immunosuppressive therapy is required in case of
      treatment failure. However, clinical remission does not necessarily imply mucosal
      healing. In parallel to the treatment of rheumatoid arthritis a novel concept is
      emerging suggesting that an early anti-inflammatory treatment can reduce
      structural changes in inflammatory bowel diseases. The studies supporting this
      novel therapeutic strategy that mucosal healing might build the future
      therapeutic goal will be discussed. In order to adjust the therapy, risk factors
      indicating a complicated disease course will be identified, resulting in the
      development of an individual disease course. The benefit of these strategies will
      be discussed together with therapy-associated complications.

PMID- 21069276
TI  - [Organizational, personnel and structural alterations due to participation in
      TraumaNetworkD DGU. The first stocktaking].
AB  - BACKGROUND: By implementation of a nationwide trauma network in Germany a high
      quality standard of technical, personnel and scientific conditions should be
      attained in hospitals participating in care for severely injured patients. All
      hospitals audited within the framework of TraumaNetwork(D) DGU are also evaluated
      for the modifications undertaken by answering a questionnaire. Using this data 
      it was possible to 1) obtain information about hitherto existing personnel and
      technical infrastructures of all participating hospitals and 2) to present first
      positive effects achieved by implementation and participating in TraumaNetwork(D)
      DGU. MATERIALS AND METHODS: The questionnaire contained 41 questions concerning
      organizational, personnel and structural changes to justify the motivation for
      participating in TraumaNetwork(D) DGU and regarding the degree of confidence with
      reference to the work of the AKUT office. Analysis of data has been carried out
      and given as a percentage of all useable questionnaires. RESULTS: Data of 138
      hospitals has been evaluated. Regarding organizational changes 29% of
      national/supraregional trauma centers made fewer adjustments than local (44%) and
      regional (55%) trauma centers. Personnel changes mainly affected participation in
      ATLS courses, cooperation with a neurosurgical department and reorganization of
      work schedules. With respect to structural changes most frequently emergency
      operating sets for emergency surgery have been established, teleradiology systems
      have been implemented and in 25% of the cases a sonography unit has been
      acquired. The rarest, but also most cost-intensive, new acquisition has been a CT
      scanner in or close to the emergency trauma room (10%). The work of the AKUT
      office has been rated altogether more satisfying by local trauma centers (mean
      2.4) than by regional and national trauma centers (mean 2.6). Prompt information
      by AKUT has been especially praised (mean 2.1). CONCLUSION: Being organized in
      trauma networks motivates hospitals to optimize their operational sequences and
      personnel and structural conditions. How much the care for multiple injured
      patients can be improved nationwide in Germany will be shown over the next few
      years. Through compulsive participation in TraumaRegister(QM) DGU (quality
      management) as a measurement for quality assurance this will be analyzed and
      evaluated scientifically.

PMID- 21069277
TI  - Predicting the accumulation of organic contaminants from soil by plants.
AB  - Analytic expressions for maximum chemical concentration attained in plants, and
      time this takes for uptake from surrounding soil were derived from a simple two
      compartment soil/water-plant model. To illustrate, for the antibiotic norflxacin
      undergoing first order loss in the soil/water phase with a rate constant of 0.544
      days-1, maximum concentration in soybean P(MAX) is predicted to occur after 2.79
      days exposure and be independent of initial soil/water concentration SW0 of 52.5
      mg kg-1 dry weight. For soybean, the relationship between P(MAX) and SW0 is
      P(MAX) = 0.047SW0, resulting in predicted maximum levels of 2.20 mg kg-1 dry
      weight. Modelled plant concentrations agreed well with experimental data (R2 =
      0.91).

PMID- 21069278
TI  - Speciation and phytoavailability of heavy metals in contaminated soils in
      Sarcheshmeh area, Kerman Province, Iran.
AB  - Heavy metal content in soil and the most abundant indigenous plant species
      (Artemisia sieberi) in Sarcheshmeh area is investigated. Sequential extraction
      analysis is carried out and phytoavailable fractions of selected heavy metals are
      also determined. The results show that heavy metals in the study area are
      potentially bioavailable. Calculated transfer factor (mean value for Cu: 5.7; As:
      8.9; Pb: 4.1; Mo: 7.2; Cd: 1.9; and Zn: 1.8) and heavy metal concentration in
      plant species indicate that metal contamination is already transferred to
      Artemisia sieberi which proved to behave like an accumulator plant and hence
      poses a serious threat to local population. Contamination is mostly the result of
      three decades of ore smelting at the Sarcheshmeh copper complex.

PMID- 21069279
TI  - Removal of 2-mercaptobenzoxazole from water as model of odorous mercaptan
      compounds by a heterogenous photocatalytic process using Ag-ZnO nanocomposite
      coated thin film on glass plate.
AB  - A photocatalytic process was evaluated for the removal of 2-Mercaptobenzoxazole
      (MBO) in wastewater. More than 90% of the MBO was removed by photocatalytic
      oxidation at about 3 h of irradiation time using Ag-ZnO nanocomposite thin film
      catalysts coated on glass by dip-coating. Ag-ZnO nanocomposite thin film was
      characterized by means of X-ray diffraction (XRD), scanning electron microscopy
      (SEM). The initial concentration of MBO was 20 ppm with optimum pH value of about
      8.0. This investigation will give a new insight to understanding the mercaptan
      photodegradation in aquatic environment.

PMID- 21069280
TI  - Concentrations of trace elements in tissues of red fox (Vulpes vulpes) and stone
      marten (Martes foina) from suburban and rural areas in Croatia.
AB  - Trace elements concentrations (As, Cd, Cu, Pb and Hg) were determined in the
      liver, kidney and muscle of 28 red fox (Vulpes vulpes) and 16 stone marten
      (Martes foina) from suburban and rural habitats from Croatia. Rural and suburban
      habitats affected Cd and Hg levels in the muscle, liver and kidney of red fox.
      Significant differences in metal concentrations in the muscle, liver and kidney
      were detected among species. Suburban stone marten accumulated the highest levels
      of trace elements (mg/kg w.w.): in muscle 0.019 for Hg; in liver 0.161 for Cd,
      36.1 for Cu and 0.349 for Pb; in kidney 1.34 for Cd and 0.318 for Pb. Values
      observed were higher than those found in suburban red fox and therefore, may
      represent an important bioindicator for the accumulation of toxic metals in
      urbanized habitats.

PMID- 21069281
TI  - Study on the new antifouling compounds in Korean coasts.
AB  - After prohibition of use of organic tin compounds, new antifouling agents have
      been used as substitute paints. In 2009, this lab re-conducted the same research
      from 2006 that focused on concentrations of chlorothalonil, dichlofluanid, and
      Irgarol in the major bays of Korea, in order to assess changes in concentrations.
      Among the new antifouling agents detected in 2006, chlorothalonil, dichlofluanid,
      and Irgarol 1051 were detected up to 4.19, 61.69, and 23.80 ng/L, respectively.
      However, in 2009, up to 67.96, 74.79, and 67.64 ng/L were detected. Compared to
      2006, there were apparent increases in the concentration of all three compounds
      in all areas where the research was conducted. These results indicate the need
      for further research regarding the hazards of these compounds.

PMID- 21069282
TI  - Environmental and occupational exposures to mercury among indigenous people in
      Dunkwa-On-Offin, a small scale gold mining area in the South-West of Ghana.
AB  - Total mercury concentrations in human hair and urine samples were determined to
      ascertain the extent of environmental and occupational mercury exposure in Dunkwa
      On-Offin, a small scale gold mining area of the central-west region of Ghana. In
      all ninety-four (94) hair and urine samples comprising of forty (40) small scale
      miners and fifty-four (54) farmers were collected and analyzed for their total
      mercury levels using the cold vapour atomic absorption spectrometry. The hair
      total mercury concentrations ranged from 0.63 to 7.19 ug/g with a mean of 2.35 +/
      1.58 ug/g for the farmers and 0.57-6.07 ug/g with a mean of 2.14 +/- 1.53 ug/g
      for the small scale gold miners. There was no significant correlation between the
      total mercury concentration and the average weekly fish diet. The total mercury
      concentrations in urine of the miners were higher than those of the farmers and
      ranged from 0.32 to 3.62 ug/L with a mean of 1.23 +/- 0.86 ug/L. The urine
      concentrations of farmers ranged from 0.075 to 2.31 ug/L with a mean of 0.69 +/-
      0.39 ug/L. Although the results indicate elevated internal dose of mercury the
      current levels of exposures do not appear to pose a significant health threat to
      the people.

PMID- 21069283
TI  - "Dioxin releases in waste incinerations and thermal processes".
AB  - The releases of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      from waste incinerators and thermal processes were investigated. The
      characteristics of mean PCDD/Fs I-TEQ concentrations and congener profiles were
      studied over the samples of water, soil, fly ash and bottom ash of individual
      source. The TEQ value for fly ash ranges from 0.013 to 17.01 pg-TEQ/g. Moreover,
      the TEQ value for bottom ash was 12.06 pg-TEQ/g and the TEQ values for the water
      samples were found to be in a consistent range from 0.41-0.56 ng-TEQ/L. In almost
      all the analyzed matrices the congener OCDD/OCDF was found in highest
      concentration raising the critical concerns over the overall PCDD/Fs emissions
      from incinerations and thermal processes.

PMID- 21069284
TI  - Polycyclic aromatic hydrocarbons (PAHs) in the surficial sediments from Lake
      Iznik (Turkey): spatial distributions and sources.
AB  - The concentrations of 12 polycyclic aromatic hydrocarbons (PAHs) were determined
      from 28 sediment samples taken from the Lake Iznik located in the north-west area
      in Turkey. Total concentration of the PAHs was observed as in the range of 17-835
      ng g-1 dry weight, with the highest values recorded offshore the cities of Iznik
      and Orhangazi, and the Soloz creek. According to the molecular indices,
      contamination of the PAHs in the lake was a mixture of the atmospheric input of
      high temperature pyrolytic processes and the petrogenic sources transported by
      the creeks. Further, the higher proportion of high molecular-weight PAHs (> 85%)
      suggests the domination of combustion-related sources. Compared to the consensus
      based sediment quality guidelines for PAHs, there are no harmful biological
      effects on the short term to aquatic life.

PMID- 21069285
TI  - Fluoride toxicity and bioaccumulation in the invasive amphipod Dikerogammarus
      villosus (Sowinsky, 1894): a laboratory study.
AB  - The tolerance of the invasive amphipod Dikerogammarus villosus to fluoride (F-)
      toxicity was examined via laboratory experiments. 96-h LC50 and 240-h NOEC values
      were estimated to be 5.8 and 0.95 mg F-/L, respectively. Average whole-body
      fluoride content in control amphipods was 27.6 MUg F-/g dry weight, whereas in
      exposed amphipods it ranged from 3,637 to 16,994 MUg F-/g dry weight. All these
      results indicate that D. villosus is a very sensitive species to fluoride
      toxicity. Overall it is concluded that the potential risk of invasion for D.
      villosus in either natural or polluted freshwater ecosystems, exhibiting
      relatively high fluoride levels (at least ten-fold higher than the average
      freshwater background level of 0.15 mg F-/L), must be low.

PMID- 21069286
TI  - Hazardous organic compounds in groundwater near Tehran automobile industry.
AB  - Potential of groundwater contamination by trichloroethylene (TCE) and other
      volatile organic compounds VOCs near car industry was conducted in this study.
      TCE, PCE, toluene, xylene, dichloromethane, cyclohexane, n-hexane and n-pentane
      were detected in all groundwaters. Mean TCE levels in groundwater ranged from
      124.37 to 1,035.9 MUg L-1 with maximum level of 1,345.7 MUg L-1. Due to the data
      obtained from conventional wastewater treatment in car factory the TCE removal
      efficiency was only 24 percent which necessitates the TCE removal by advanced
      treatment processes before the use of well water.

PMID- 21069287
TI  - Accuracy of a transcutaneous carbon dioxide pressure monitoring device in
      emergency room patients with acute respiratory failure.
AB  - PURPOSE: Transcutaneous CO(2) monitors are widely used in neonatal ICUs. Until
      recently, these devices performed poorly in adults. Recent technical
      modifications have produced transcutaneous CO(2) monitors that have performed
      well in adults with chronic illnesses. We evaluated the accuracy of one of these
      devices, the TOSCA((r)) 500, in adults admitted to an emergency department for
      acute respiratory failure. METHODS: We prospectively collected 29 pairs of
      simultaneous transcutaneous arterial CO(2) (PtcCO(2)) and arterial CO(2)
      (PaCO(2)) values in 21 consecutive adults with acute respiratory failure (acute
      heart failure, n = 6; COPD exacerbation, n = 8; acute pneumonia, n = 6; and
      pulmonary embolism, n = 1). Agreement between PaCO(2) and PtcCO(2) was evaluated
      using the Bland-Altman method. RESULTS: Mean arterial oxygen saturation was 90%,
      arterial oxygen tension ranged from 32 to 215 mmHg, and PaCO(2) ranged from 23 to
      84 mmHg. The mean difference between PaCO(2) and PtcCO(2) was 0.1 mmHg, and the
      Bland-Altman limits of agreement (bias +/- 1.96 SD) ranged from -6 to 6.2 mmHg.
      None of the patients experienced adverse effects from heating of the device
      clipped to the earlobe. CONCLUSION: PtcCO(2) showed good agreement with PaCO(2)
      in adults with acute respiratory failure.

PMID- 21069288
TI  - Prone or PEEP, PEEP and prone.

PMID- 21069289
TI  - Non-invasive ventilation with balloon dilatation of severe subglottic stenosis in
      a 10-month infant.

PMID- 21069290
TI  - Intravenous sildenafil for postoperative pulmonary hypertension in children with
      congenital heart disease.
AB  - PURPOSE: To evaluate the efficacy and safety of intravenous sildenafil for
      immediate postoperative pulmonary hypertension (PH) in pediatric patients
      undergoing congenital heart surgery. METHODS: A double-blind, multicenter,
      placebo-controlled, dose-ranging, parallel-group trial was conducted. Patients
      were randomized to one of three doses of intravenous sildenafil, or placebo, for
      a minimum of 24 h. RESULTS: The study was heavily underpowered. Whereas
      enrollment of 228 patients (57 per treatment arm) was required to achieve the
      sample size estimate to detect difference between arms, the sponsor terminated
      the study after 15 months owing to slow patient accrual. Seventeen patients
      (median age 5 months) experiencing postoperative PH were randomized and treated,
      five with placebo and four each with low-, medium-, and high-dose sildenafil. In
      the first 24 h, 40% of placebo and 17% of sildenafil patients required additional
      therapy (p = 0.330). Median time to extubation (3 versus 8 days, p = 0.023) and
      intensive care unit stay (6 versus 15 days, p = 0.008) were shorter for
      sildenafil patients. Mean +/- standard deviation systolic pulmonary artery
      pressure was reduced with sildenafil (46 +/- 11 to 35 +/- 6 mmHg, p = 0.027
      versus placebo). No adverse events or systemic hypotension were attributed to
      sildenafil. CONCLUSION: Intravenous sildenafil reduced pulmonary artery pressure
      and shortened time to extubation and intensive care unit stay in children with
      postoperative PH.

PMID- 21069291
TI  - Optimal duration of urinary catheterization after anterior colporrhaphy.
AB  - INTRODUCTION AND HYPOTHESIS: The optimal duration of urethral catheterization
      during and after pelvic reconstructive surgery is not established. This study
      investigated the optimal duration of urinary catheterization in patients
      undergoing anterior vaginal repair with or without other vaginal surgeries.
      METHODS: A total of 90 patients were included from April 2007 to March 2008. They
      were randomly divided into 2, 3, and 4 days urinary catheterization groups based
      on the color of the questionnaire papers they blindly chose. After catheter
      removal, the amount of post-void residual urine was used to measure the efficacy
      of bladder emptying. Differences between groups were determined using Chi-square
      test, Fisher's exact test, or Kruskal-Wallis test, as appropriate. RESULTS: No
      significant differences were found in the amount of post-void residual urine
      between the three catheterization groups. CONCLUSIONS: Our findings suggest that
      the duration of urethral catheterization after anterior colporrhaphy need not
      exceed 2 days.

PMID- 21069292
TI  - Secular decreases in fracture rates 1986-2006 for Manitoba, Canada: a population
      based analysis.
AB  - SUMMARY: We examined trends in fracture rates over 20 years in the Province of
      Manitoba, Canada. Hip fractures, major low-trauma fractures, and high-trauma
      fractures declined significantly from 1986 to 2006. INTRODUCTION: Secular
      decreases in hip fracture rates have been reported in some countries. Whether
      this phenomenon applies to other fracture sites is not well described. METHODS:
      We used 20 years of data from the Population Health Research Data Repository for
      the Province of Manitoba, Canada. Age-adjusted fracture rates were calculated for
      men and women age 50 years and older 1986-2006 according to fracture site and
      mechanism (presence/absence of external injury codes). Generalized linear models
      with generalized estimating equations were used to derive adjusted annual rates
      and test for linear change in men and women. RESULTS: Major low-trauma fractures
      (hip, forearm, spine, and humerus) showed a significant annual linear decline in
      women (-1.2% [95% CI, -0.7% to -1.8%]) and in men (-0.4% [95% CI, -0.7% to 
      0.2%]). Hip fracture showed a significant annual decline for both sexes, while
      forearm and humerus fractures showed a significant decline only in women. The
      only fracture category that did not show a significant annual decline in either
      sex was the spine. The observed annual reduction in high-trauma fractures was
      even larger and did not show a sex difference (-1.8% [95% CI, -2.8% to -0.7%]).
      CONCLUSION: We observed a decrease in both low-trauma and high-trauma fracture
      rates over the study period. This decline was apparent in years prior to
      widespread osteoporosis testing or availability of modern pharmacotherapy.

PMID- 21069293
TI  - Hip fracture incidence in Lebanon: a national registry-based study with reference
      to standardized rates worldwide.
AB  - Crude incidence rates for hip fractures in individuals aged 50 and above in
      Lebanon were determined using data from the national hip fracture registry. For
      the years 2006-2008, crude rates varied between 164 and 188/100,000 for females
      and between 88 and 106 per 100,000 for males. Using the US 2000 white population
      as a reference, the calculated age-standardized rates were closest to rates
      derived for southern Europe. INTRODUCTION: Owing to the demographic explosion, it
      is projected that the rates of hip fractures would increase the most in the
      Middle East and Asia. Few are the population-based studies investigating the
      incidence of hip fractures in the region. METHODS: Using the Ministry of Health
      registry data, this population-based study evaluated the incidence of hip
      fractures in individuals aged 50 and above in Lebanon for the years 2006, 2007,
      and 2008. RESULTS: Hip fracture crude incidence rates varied across the years
      between 164 and 188 per 100,000 for females and between 88 and 106 per 100,000
      for males, with a female/male ratio of 1.6-2.1. The overall mean age (SD) for hip
      fractures was 75.9 (9.2), 76.8 (9.0), and 77.0 (9.9) years in females in 2006,
      2007, and 2008, respectively, and 74.4 (11.6), 76.3 (10.3), and 74.0 (12.1) years
      in males, respectively. Using the US 2000 white population as a reference, the
      age-standardized rates were 370.4, 335.1, and 329.0 for females and 109.7, 134.1,
      and 128.7 for males, for the years 2006, 2007, and 2008, respectively.
      CONCLUSIONS: The hip fracture age-standardized incidence rates in the Lebanese
      subjects receiving Ministry of Health coverage were lower than those found in
      northern Europe and the US and closest to rates derived for southern Europe.

PMID- 21069294
TI  - Preventing osteoporosis with a tissue selective estrogen complex (TSEC)
      containing bazedoxifene/conjugated estrogens (BZA/CE).
AB  - Hormone therapy classically consists of an estrogen with an added progestin;
      however, concerns have been raised about the potential negative effects of
      progestin. The recent realization that estrogen agonist-antagonists or selective
      estrogen receptor modulators might be paired with estrogens instead of a
      progestin has led to the development of a novel form of menopausal therapy called
      tissue selective estrogen complex (TSEC). A TSEC is the pairing of a selective
      estrogen receptor modulator (SERM) with estrogen(s). The TSEC containing
      conjugated estrogens (CE) and the SERM, bazedoxifene (BZA), has reached clinical
      development. This short review outlines the effects of this particular TSEC,
      which maintains or increases bone mass in women at high risk for osteoporosis,
      and has clinical qualities of a promising new menopausal therapy. Randomized,
      double-blind, placebo-controlled phase 3 trials in postmenopausal women showed
      that, in addition to bone preservation, BZA/CE was shown to relieve hot flushes
      and treat vulvar-vaginal atrophy and its symptoms, with a good safety and
      tolerability profile.

PMID- 21069295
TI  - Vertebral fracture risk (VFR) score for fracture prediction in postmenopausal
      women.
AB  - SUMMARY: Early prognosis of osteoporosis risk is not only important to individual
      patients but is also a key factor when screening for osteoporosis drug trial
      populations. We present an osteoporosis fracture risk score based on vertebral
      heights. The score separated individuals who sustained fractures (by follow-up
      after 6.3 years) from healthy controls at baseline. INTRODUCTION: This case
      control study was designed to assess the ability of three novel fracture risk
      scoring methods to predict first incident lumbar vertebral fractures in
      postmenopausal women matched for classical risk factors such as BMD, BMI, and
      age. METHODS: This was a case-control study of 126 postmenopausal women, 25 of
      whom sustained at least one incident lumbar fracture and 101 controls that
      maintained skeletal integrity over a 6.3-year period. Three methods for fracture
      risk assessment were developed and tested. They are based on anterior, middle,
      and posterior vertebral heights measured from vertebrae T12-L5 in lumbar
      radiographs at baseline. Each score's fracture prediction potential was
      investigated in two variants using (1) measurements from the single most deformed
      vertebra or (2) average measurements across vertebrae T12-L5. Emphasis was given
      to the vertebral fracture risk (VFR) score. RESULTS: All scoring methods
      demonstrated significant separation of cases from controls at baseline.
      Specifically, for the VFR score, cases and controls were significantly different
      (0.67 +/- 0.04 vs. 0.35 +/- 0.03, p < 10 (-6)) with an AUC of 0.82. Dividing the
      VFR scores into tertiles, the fracture odds ratio for the highest versus lowest
      tertile was 35 (p < 0.001). Sorting the combined case-control group according to
      VFR score resulted in 90% of cases in the top half. CONCLUSION: At baseline, the
      three scores separated cases from controls and, especially, the VFR score appears
      to be predictive of fractures. Control experiments, however also, indicate that
      VFR-based fracture prediction is operator/annotator dependent and high-quality
      annotations are needed for good fracture prediction.

PMID- 21069296
TI  - Serum level of pepsinogen significantly associated with gastric distress induced
      by amino-bisphosphonates.
AB  - To elucidate whether serum levels of pepsinogens are associated with the
      occurrence of gastrointestinal adverse events induced by amino-bisphosphonates
      (amino-BP), the serum levels of pepsinogen were measured in amino-BP users. Our
      results indicate that measurement of pepsinogen I is useful in predicting gastric
      distress induced by amino-BP in osteoporosis. INTRODUCTION: To elucidate whether
      serum levels of pepsinogens are associated with the occurrence of
      gastrointestinal adverse events induced by amino-BP, the serum levels of
      pepsinogen I and II were measured in amino-BP users. METHODS: When the patients
      complained of gastric distress symptoms during the first 6 months after amino-BP
      use resulting in discontinuation of the drug, endoscopical examinations were
      performed to assess whether gastric lesions were present. A total of 223 amino-BP
      users were enrolled in the study, of which 47 patients refused to take the drug
      due to gastric distress symptoms. The remaining 176 patients did not complain of
      any gastric distress. RESULTS: Among 47 patients, eight patients showed obvious
      gastric lesions such as gastric or duodenal ulcers and acute gastric mucosal
      lesions in the endoscopical examination. The remaining 39 patients did not show
      any gastric lesions. The possible confounding factors, such as a Helicobactor
      pylori infection or concurrent use of ulcerogenic agents, did cause not affect
      gastric distress in amino-BP users. The serum pepsinogen I level was
      significantly associated with severity of the gastric lesion 46.8 +/- 27.7, 60.8
      +/- 32.4, and 103.4 +/- 49.2 ng/ml for patients without any gastric distress,
      with gastric distress accompanied no gastric lesions, and with gastric distress
      accompanied gastric lesions, respectively. CONCLUSIONS: ROC analysis revealed
      that the cutoff value of pepsinogen I for expectation of gastric regions was 76.8
      ng/ml. The results clearly indicate that measurement of pepsinogen I may be
      useful in predicting gastric distress induced by amino-BP in osteoporosis.

PMID- 21069297
TI  - Identification and characterization of gerPI and gerPII involved in epoxidation
      and hydroxylation of dihydrochalcolactone in Streptomyces species KCTC 0041BP.
AB  - The macrolide antibiotics are biosynthesized by initial assembly of a
      macrolactone ring, followed by a series of post-polyketide (PKS) modifications.
      In general, the additional hydroxyl or epoxy groups are installed by cytochrome
      P450 enzymes, improving the bioactivity profile through structural
      diversification of natural products. The biosynthetic gene cluster for the 16
      membered macrolide antibiotic dihydrochalcomycin (DHC) has been cloned from
      Streptomyces sp. KCTC 0041BP. Three cytochrome P450 genes are found in the DHC
      biosynthetic gene (ger) cluster. Two P450 enzymes were characterized from this
      cluster. Disruption of gerPI accumulated predominantly 12,13-de
      epoxydihydrochalcomycin while disruption of gerPII accumulated 8-dehydroxy-12,13
      de-epoxydihydrochalcomycin; DHC production was abolished in both cases. The
      results suggest that GerPII P450 catalyzes hydroxylation at the C(8) position
      followed by an epoxidation reaction catalyzed by GerPI P450 at the C(12)-C(13)
      position.

PMID- 21069298
TI  - Thermal dependence of Raman descriptors of ceramides. Part II: effect of chains
      lengths and head group structures.
AB  - The outermost layer of the mammalian skin, the stratum corneum (SC), represents
      the main skin barrier. The SC lipids have a very exceptional composition, as the
      main lipid classes are ceramides (CER), long-chain fatty acids and cholesterol.
      Information on the function of each CER subclass and on the relation between CER
      lipid organisation and composition is of great importance to unravel the
      mechanism controlling the skin barrier function. Raman spectroscopy has been
      increasingly used for the study of intra- and inter-molecular structures of long
      chain lipid compounds. In this study, we employed Raman spectroscopy to evaluate
      the effect of (1) the chain length and (2) the polar head architecture on the
      conformational order and organisational behaviour of CERs. The relation between
      the structure and the stability of the organisation was studied by monitoring the
      thermotropic response of each CER in the temperature range between 25 and 95 
      degrees C. This work enabled the determination of a correlation between the
      gauche/trans ratio in the nuCC region and the state of the lateral packing.
      Moreover, it was shown that -OH groups in the alpha position of the fatty acids
      reduce the stability while long alkyl chains reinforces the intra- and inter
      chains order.

PMID- 21069299
TI  - Application of ATR-far-infrared spectroscopy to the analysis of natural resins.
AB  - This study proposes FTIR spectroscopy in the far-infrared region (FarIR) as an
      alternative method for the characterisation of natural resins. To this purpose,
      standards of natural resins belonging to four different categories
      (sesquiterpenic, i.e. elemi, shellac; diterpenic, i.e. colophony, Venice
      turpentine; diterpenic with polymerised components, i.e. copal, sandarac;
      triterpenic, i.e. mastic and dammar) used as paint varnishes have been analysed
      by FarIR spectroscopy in ATR mode. Discrimination between spectral data and
      repeatability of measurements have been magnified and verified using principal
      component analysis, in order to verify the effectiveness of the method in
      distinguishing the four resin categories. The same samples were analysed in the
      MidIR range, but the spectral differences between the different categories were
      not evident. Moreover, the method has been tested on historical samples from the
      painting "La Battaglia di Cialdiran" (sixteenth century) and from a gilded
      leather (seventeenth century). In the first case, FarIR spectroscopy allowed
      confirmation of the results obtained by analytical pyrolysis. In the latter,
      FarIR spectroscopy proved successfully, effective in the identification of the
      superficial resin layer that could not be detected with the bulk chromatographic
      analyses.

PMID- 21069300
TI  - A multi-channel bioluminescent bacterial biosensor for the on-line detection of
      metals and toxicity. Part I: design and optimization of bioluminescent bacterial
      strains.
AB  - This study describes the construction of inducible bioluminescent strains via
      genetic engineering along with their characterization and optimization in the
      detection of heavy metals. Firstly, a preliminary comparative study enabled us to
      select a suitable carbon substrate from pyruvate, glucose, citrate, diluted Luria
      Bertani, and acetate. The latter carbon source provided the best induction ratios
      for comparison. Results showed that the three constructed inducible strains,
      Escherichia coli DH1 pBzntlux, pBarslux, and pBcoplux, were usable when
      conducting a bioassay after a 14-h overnight culture at 30  degrees C. Utilizing
      these sensors gave a range of 12 detected heavy metals including several cross
      detections. Detection limits for each metal were often close to and sometimes
      lower than the European standards for water pollution. Finally, in order to
      maintain sensitive bacteria within the future biosensor-measuring cell, the
      agarose immobilization matrix was compared to polyvinyl alcohol (PVA). Agarose
      was selected because the detection limits of the bioluminescent strains were not
      affected, in contrast to PVA. Specific detection and cross-detection ranges
      determined in this study will form the basis of a multiple metals detection
      system by the new multi-channel Lumisens3 biosensor.

PMID- 21069302
TI  - pH optimization for a reliable quantification of brain tumor cell and tissue
      extracts with (1)H NMR: focus on choline-containing compounds and taurine.
AB  - The aim of this study was to define the optimal pH for (1)H nuclear magnetic
      resonance (NMR) spectroscopy analysis of perchloric acid or methanol-chloroform
      water extracts from brain tumor cells and tissues. The systematic study of the
      proton chemical shift variations as a function of pH of 13 brain metabolites in
      model solutions demonstrated that recording (1)H NMR spectra at pH 10 allowed
      resolving resonances that are overlapped at pH 7, especially in the 3.2-3.3 ppm
      choline-containing-compounds region. (1)H NMR analysis of extracts at pH 7 or 10
      showed that quantitative measurements of lactate, alanine, glutamate, glutamine
      (Gln), creatine + phosphocreatine and myo-inositol (m-Ino) can be readily
      performed at both pHs. The concentrations of glycerophosphocholine,
      phosphocholine and choline that are crucial metabolites for tumor brain
      malignancy grading were accurately measured at pH 10 only. Indeed, the resonances
      of their trimethylammonium moieties are cleared of any overlapping signal,
      especially those of taurine (Tau) and phosphoethanolamine. The four non-ionizable
      Tau protons resonating as a singlet in a non-congested spectral region permits an
      easier and more accurate quantitation of this apoptosis marker at pH 10 than at
      pH 7 where the triplet at 3.43 ppm can be overlapped with the signals of glucose
      or have an intensity too low to be measured. Glycine concentration was determined
      indirectly at both pHs after subtracting the contribution of the overlapped
      signals of m-Ino at pH 7 or Gln at pH 10.

PMID- 21069301
TI  - Enhanced detection of olefins using ambient ionization mass spectrometry: Ag+
      adducts of biologically relevant alkenes.
AB  - Spray solvent doped with silver ions increases the ease of olefin detection by
      desorption electrospray ionization (DESI). Characteristic silver adducts were
      generated in up to 50 times greater abundance when compared to conventional DESI
      spray solvents for the biologically significant olefin, arachidonic acid, in the
      positive ion mode. In the analysis of 26 lipids, silver adduct formation was
      highly favorable for fatty acids, fatty acid esters and prostaglandins but not
      applicable to some other classes (e.g., polar lipids such as ceramide and its
      derivative cerebroside sulfate). An investigation exploring competitive Ag(+)
      cationization with a mixture of components demonstrated that polyunsaturated
      compounds form Ag(+) adducts most readily. Silver cationization allowed the
      distinction between three sets of isomers in the course of multiple-stage
      collision-induced dissociation, so providing insight into the location of the
      olefin bonds. A silver ion-doped solvent was used in DESI imaging of normal and
      tumor canine bladder tissue sections. The Ag(+) fatty acid adducts permitted post
      facto differentiation between the normal and tumor regions. In addition, silver
      adduct formation in the course of DESI imaging of tissue sections revealed the
      presence of triacylglycerides, a class of compounds not previously identified
      through DESI imaging. A simple silver nitrate spray solvent has the potential to
      further improve DESI analysis of unsaturated biomolecules and other molecules
      containing pi-bonds through selective silver cationization.

PMID- 21069303
TI  - Solution to the uncooked egg challenge.

PMID- 21069304
TI  - (1)H NMR signal at 2.10 ppm in the spectrum of KMnO(4)-bleached heparin sodium:
      identification of the chemical origin using an NMR-only approach.
AB  - The recently revised European Pharmacopeia and US Pharmacopeia heparin sodium
      monographs include nuclear magnetic resonance (NMR) tests on both identity and
      purity. In KMnO(4)-bleached heparin, an unidentified NMR signal is present at
      2.10 ppm at a level of 15-20% of the mean of signal height of the major
      glucosamine (GlcNAc/GlcNS,6S) anomeric proton signal at 5.42 ppm and of the major
      iduronic acid (IdoA2S) anomeric proton signal at 5.21 ppm. According to the new
      monographs, no unidentified signals greater than 4% should be detected at that
      position. Thus, the material did not meet the acceptance criterion. The signal at
      2.10 ppm has been present at the same level in all released MSD KMnO(4)-bleached
      heparin sodium batches analyzed over the past 10 years. The signal is a result of
      the KMnO(4) bleaching. No (oversulfated) chondroitin sulfate or dermatan sulfate
      was detected in this material. A comprehensive NMR study using long-range
      heteronuclear 2D techniques identifies this signal at 2.10 ppm as originating
      from the acetyl methyl group of (6-sulfated) 2-N-acetyl-2-deoxy-glucono-1,5
      lactone. This modified monosaccharide is formed by the KMnO(4) oxidation of the
      reducing end of a terminal N-acetylglucosamine.

PMID- 21069305
TI  - Effects of electrical coupling among layer 4 inhibitory interneurons on contrast
      invariant orientation tuning.
AB  - Simulations of orientation selectivity in visual cortex have shown that layer 4
      complex cells lacking orientation tuning are ideal for providing global
      inhibition that scales with contrast in order to produce simple cells with
      contrast-invariant orientation tuning (Lauritzen and Miller in J Neurosci
      23:10201-10213, 2003). Inhibitory cortical cells have been shown to be
      electrically coupled by gap junctions (Fukuda and Kosaka in J Neurosci 120:5-20,
      2003). Such coupling promotes, among other effects, spike synchronization and
      coordination of postsynaptic IPSPs (Beierlein et al. in Nat Neurosci 3:904-910,
      2000; Galarreta and Hestrin in Nat Rev Neurosci 2:425-433, 2001). Consequently,
      it was expected (Miller in Cereb Cortex 13:73-82, 2003) that electrical coupling
      would promote nonspecific functional responses consistent with the complex
      inhibitory cells seen in layer 4 which provide broad inhibition in response to
      stimuli of all orientations (Miller et al. in Curr Opin Neurobiol 11:488-497,
      2001). This was tested using a mechanistic modeling approach. The orientation
      selectivity model of Lauritzen and Miller (J Neurosci 23:10201-10213, 2003) was
      reproduced with and without electrical coupling between complex inhibitory
      neurons. Although extensive coupling promotes uniform firing in complex cells,
      there were no detectable improvements in contrast-invariant orientation
      selectivity unless there were coincident changes in complex cell firing rates to
      offset the untuned excitatory component that grows with contrast. Thus, changes
      in firing rates alone (with or without coupling) could improve contrast-invariant
      orientation tuning of simple cells but not synchronization of complex inhibitory
      neurons alone.

PMID- 21069306
TI  - Is tracing or copying better when learning to reproduce a pattern?
AB  - Learning to write requires the repeated manual production of spatial patterns. It
      remains unclear whether tracing or copying provides better training: tracing
      provides accurate and immediate performance feedback, whereas copying may require
      greater use of memory and recall during training. We asked sixteen adults to copy
      or trace novel patterns then reproduce these from memory using a stylus and
      tablet PC. A week later, a retention test was performed. Sophisticated analyses
      indexed the extent to which participants had learned the dimensions and shape of
      patterns. We found that participants: (a) showed better shape and dimensional
      accuracy when tracing; (b) had better shape and dimensional retention immediately
      after tracing; (c) showed no differences between copying and tracing in their
      ability to redraw the pattern (shape or dimensions) 1 week later. Our methods
      provide a useful starting point for examining training and feedback on the
      generation and recall of spatial patterns.

PMID- 21069307
TI  - Modulation of corticomotor excitability by an I-wave intervention delivered
      during low-level voluntary contraction.
AB  - Transcranial magnetic stimulation (TMS) interventions that modulate cortical
      plasticity may achieve a more functional benefit if combined with neuro
      rehabilitation therapies. With a TMS protocol targeting I-wave dynamics, it is
      possible to deliver stimuli while a subject performs a motor task, and this may
      more effectively target functional networks related to the task. However, the
      efficacy of this intervention during a simple task such as a low-level voluntary
      contraction is not known. We delivered paired-pulse TMS at an inter-pulse
      interval (IPI) of 1.5 ms for 15 min while subjects performed a 10 +/- 2.5%
      voluntary contraction of the first dorsal interosseous (FDI) muscle and made
      motor evoked potential (MEP) amplitude and short-interval intracortical
      facilitation (SICF) curve measurements. Pre-intervention SICF curves showed only
      a single peak at 1.3-1.5 ms IPI. During the intervention, MEP amplitude steadily
      increased (P < 0.001) to 137 +/- 13% of its initial value. After the
      intervention, SICF curves were increased in amplitude (P < 0.001) and later peaks
      emerged at 2.8 and 4.3 ms IPIs. A control experiment, replacing paired-pulse
      stimulation with single-pulse stimulation showed no effect on MEP amplitude (P =
      0.951). We conclude that the I-wave intervention can be administered concurrently
      with a simple motor task and that it acts by increasing trans-synaptic efficacy
      across a number of I-waves. The ability to perform a motor task simultaneously
      with a TMS intervention could confer a degree of specificity to the induced
      excitability changes and may be beneficial for functional neuro-rehabilitation
      programs built around motor learning and retraining.

PMID- 21069308
TI  - Bilateral neuromuscular plasticity from unilateral training of the ankle
      dorsiflexors.
AB  - Training a muscle group in one limb yields strength gains bilaterally-the so
      called cross-education effect. However, to date there has been little study of
      the targeted application of this phenomenon in a manner relevant to clinical
      rehabilitation. For example, it may be applicable post-stroke, where hemiparesis
      leads to ankle flexor weakness. The purpose of this study was to examine the
      effects of high-intensity unilateral dorsiflexion resistance training on agonist
      (tibialis anterior, TA) and antagonist (plantarflexor soleus, SOL) muscular
      strength and H-reflex excitability in the trained and untrained limbs. Ankle
      flexor and extensor torque, as well as SOL and TA H-reflexes evoked during low
      level contraction, were measured before and after 5 weeks of dorsiflexion
      training (n = 19). As a result of the intervention, dorsiflexor maximal voluntary
      isometric contraction force (MVIC) significantly increased (P < 0.05) in both the
      trained and untrained limbs by 14.7 and 8.4%, respectively. No changes in
      plantarflexor MVIC force were observed in either limb. Significant changes in H
      reflex excitability threshold were also detected: H(@thresh) significantly
      increased in the trained TA and SOL; and H(@max) decreased in both SOL muscles.
      These findings reveal that muscular crossed effects can be obtained in the ankle
      dorsiflexor muscles and provide novel information on agonist and antagonist
      spinal adaptations that accompany unilateral training. It is possible that the
      ability to strengthen the ankle dorsiflexors bilaterally could be applied in post
      stroke rehabilitation, where ankle flexor weakness could be counteracted via
      dorsiflexor training in the less-affected limb.

PMID- 21069309
TI  - Efficacy of tolterodine for medical treatment of intramural ureteral stone with
      vesical irritability.
AB  - We evaluated the clinical results of tolterodine in treating impacted stones in
      the intramural ureter with symptoms of vesical irritability. A total of 80
      patients with intramural ureter stones were included in the study from December
      2007 to November 2009. Patients were randomly divided into two groups. The 41
      patients in group A were given a watchful waiting and served as control group.
      Group B received 2 mg tolterodine (twice a day). Both groups were followed up for
      2 weeks. The stone expulsion rate and time and the number of pain episodes were
      obtained. Subjects rated the urgency associated with each micturition using the
      Urinary Sensation Scale (USS). Pain descriptions were recorded by the patients
      using the Visual Analog Scale (VAS). The stone expulsion rate in groups A and B
      was 56.1 and 56.4%, respectively (P = 0.98). The mean numbers of renal colic
      episodes of patients in groups A and B had experienced 4.5 and 1.7, respectively.
      The USS for groups A and B in 3 and 7 days were 2.89 +/- 0.56, 1.29 +/- 0.60;
      1.98 +/- 0.79, 1.09 +/- 0.3, respectively (P < 0.001). Statistically significant
      difference was found between groups A and B in relation to the VAS score on days
      3 and 7, respectively (P < 0.001). While our study demonstrated no improvement in
      expulsion rate, Tolterodine reduced the common symptoms of frequency, urgency,
      intensity of the pain episodes and discomfort often associated with intramural
      ureter stone.

PMID- 21069310
TI  - Ultrasound-guided X-ray free percutaneous nephrolithotomy for treatment of simple
      stones in the flank position.
AB  - The purpose of this study was to examine the effectiveness and safety of
      percutaneous nephrolithotomy with ultrasonography-guided renal access in the
      flank position without the use of fluoroscopy in any stage of the procedure.
      Percutaneous nephrolithotomy was performed in flank position under the guidance
      of ultrasound (USG) without the use of fluoroscopy between December 2008 and
      January 2010 on 43 patients who had kidney stones bigger than 20 mm. Access to
      the kidney's proper calyx was achieved by dilatation through the guide wire
      placed after insertion of the needle through the needle director under the
      guidance of transrectal ultrasound probe placed on the patient's flank area. A
      convex USG probe was used for imaging during dilatation and lithotripsy instead
      of fluoroscopy. Access to the targeted calyx was achieved successfully in all
      patients (100%). The percentage stone free rate was 86.1% (37 patients). Residual
      stones were detected in six patients. Their dimensions ranged from 5 to 12 mm.
      The mean stone diameter was 29 (20-41) mm, duration of surgery was 87.1 +/- 43.2
      (55-210) min and duration of hospital stay was 3.1 (2-8) days. Blood transfusions
      were given to two patients; none of the patients had major intraoperative or
      postoperative complications. In comparison with standard percutaneous
      nephrolithotomy, percutaneous nephrolithotomy in flank position under
      ultrasonographic imaging instead of using fluoroscopy seems to be safe and
      effective. This procedure has to be limited to selected cases with one or maximum
      two big stones in the pelvis or in a single calyx in absence of complex
      intrarenal anatomy. Both surgical team and the patients were protected from the
      harmful effects of radiation. Regarding anesthesia, flank position is more
      comfortable for the patient than prone position.

PMID- 21069311
TI  - Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its
      constituents khellin and visnagin in hyperoxaluric rats.
AB  - In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") are
      traditionally used by patients with urolithiasis. The aim of this study was to
      evaluate whether oral administration of an aqueous extract prepared from the
      fruits of A. visnaga as well as two major constituents khellin and visnagin could
      prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in
      male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride
      via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally
      administered for 14 days. The histopathological examination of the kidneys
      revealed that KE significantly reduced the incidence of calcium oxalate (CaOx)
      crystal deposition. In addition, KE significantly increased urinary excretion of
      citrate along with a decrease of oxalate excretion. Comparable to the extract,
      khellin and visnagin significantly reduced the incidence of CaOx deposition in
      the kidneys. However, both compounds did not affect urinary citrate or oxalate
      excretion indicating a mechanism of action that differs from that of the extract.
      For KE, a reasonably good correlation was observed between the incidence of
      crystal deposition, the increase in citrate excretion and urine pH suggesting a
      mechanisms that may interfere with citrate reabsorption. In conclusion, our data
      suggest that KE and its compounds, khellin and visnagin, may be beneficial in the
      management of kidney stone disease caused by hyperoxaluria but that it is likely
      that different mechanism of action are involved in mediating these effects.

PMID- 21069312
TI  - Effects of an environmentally realistic pesticide mixture on Daphnia magna
      exposed for two generations.
AB  - Daphnia magna were exposed under semistatic conditions (i.e., conditions taking
      natural degradation into account) to a pesticide mixture consisting of a
      pyrethroid insecticide (cyfluthrin) and a pre-emergent herbicide (diuron) as well
      as pesticides individually using a full life cycle exposure (21 days).
      Subsequently, offspring from the second reproductive brood were used to continue
      exposure for a second generation. Survival, time to first brood, total number of
      offspring produced, number of broods produced, growth rate, and population growth
      rate were recorded for each generation and concentration. Significant differences
      existed between F0 and F1 D. magna for survival, in which F1 were less sensitive
      to pesticide mixtures than F0. In addition, F1 D. magna were significantly
      smaller than F0, which resulted in longer time to first brood. There were no
      differences in any end point examined between D. magna exposed to the pesticide
      mixture and diuron alone, although differences existed in survival, total number
      of offspring, total number of broods, and population growth rate when F0 D. magna
      were exposed to cyfluthrin alone. This study illustrates the utility of a two
      generation study design that may more fully reflect, and more accurately predict,
      population level effects of pesticide exposures to short-lived aquatic organisms.

PMID- 21069313
TI  - The pharmaceutical use of permethrin: sources and behavior during municipal
      sewage treatment.
AB  - Permethrin entered use in the 1970s as an insecticide in a wide range of
      applications, including agriculture, horticultural, and forestry, and has since
      been restricted. In the 21st century, the presence of permethrin in the aquatic
      environment has been attributed to its use as a human and veterinary
      pharmaceutical, in particular as a pedeculicide, in addition to other uses, such
      as a moth-proofing agent. However, as a consequence of its toxicity to fish,
      sources of permethrin and its fate and behavior during wastewater treatment are
      topics of concern. This study has established that high overall removal of
      permethrin (approximately 90%) was achieved during wastewater treatment and that
      this was strongly dependent on the extent of biological degradation in secondary
      treatment, with more limited subsequent removal in tertiary treatment processes.
      Sources of permethrin in the catchment matched well with measured values in crude
      sewage and indicated that domestic use accounted for more than half of the load
      to the treatment works. However, removal may not be consistent enough to achieve
      the environmental quality standards now being derived in many countries even
      where tertiary treatment processes are applied.

PMID- 21069314
TI  - Development of an autonomously replicating linear vector of the yeast
      Cryptococcus humicola by using telomere-like sequence repeats.
AB  - The yeast Cryptococcus humicola has several attractive properties for practical
      applications such as in bioremediation and as a source of industrially useful
      enzymes and compounds. We have developed an autonomously replicating vector of C.
      humicola to improve its properties. We initially tried to isolate an autonomously
      replicating sequence (ARS) from genomic DNA by transformation using a genomic DNA
      library. We obtained a candidate plasmid vector harboring an ARS that gave high
      transformation efficiency. Southern blot analysis of transformants revealed the
      autonomous replication of the introduced vector in some transformants. However,
      the vector was not only variously altered in length but also linearized. PCR
      analysis indicated that a telomere-like sequence repeat (TTAGGGGG)( n ) was added
      to the termini of linearized vector. Thus, we constructed an autonomously
      replicating linear vector having ten repeats of the telomere-like sequence at
      both ends. The vector transformed the yeast cells with high transformation
      efficiency (3230 CFU/MUg of DNA), which was approximately 25-fold higher than
      that of a control vector lacking the repeats, and was autonomously replicated at
      a roughly constant size. The copy number was estimated to be less than one copy,
      and Ura(+) mitotic stability varied widely among the transformants and was
      related to plasmid segregation efficiency.

PMID- 21069315
TI  - A novel L-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4
      hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid.
AB  - 4-Hydroxyisoleucine (HIL) found in fenugreek seeds has insulinotropic and anti
      obesity effects and is expected to be a novel orally active drug for insulin
      independent diabetes. Here, we show that the newly isolated strain Bacillus
      thuringiensis 2e2 and the closely related strain B. thuringiensis ATCC 35646
      operate a novel metabolic pathway for L-isoleucine (L-Ile) via HIL and 2-amino-3
      methyl-4-ketopentanoic acid (AMKP). The HIL synthesis was catalyzed
      stereoselectively by an alpha-ketoglutaric acid-dependent dioxygenase and to be
      useful for efficient production of a naturally occurring HIL isomer, (2S,3R,4S)
      HIL. The (2S,3R,4S)-HIL was oxidized to (2S,3R)-AMKP by a NAD(+)-dependent
      dehydrogenase. The metabolic pathway functions as an effective bypass pathway
      that compensates for the incomplete tricarboxylic acid (TCA) cycle in Bacillus
      species and also explains how AMKP, a vitamin B(12) antimetabolite with
      antibiotic activity, is synthesized. These novel findings pave a new way for the
      commercial production of HIL and also for AMKP.

PMID- 21069316
TI  - Intrathoracic splenosis: evaluation by 99mTc-labelled heat-denatured erythrocyte
      SPECT/CT.

PMID- 21069317
TI  - Wide beam reconstruction for half-dose or half-time cardiac gated SPECT
      acquisitions: optimization of resources and reduction in radiation exposure.
AB  - PURPOSE: A new iterative reconstruction algorithm (WBRTM) has been recently
      proposed for cardiac single photon emission computed tomography (SPECT). The
      WBRTM technology is designed to reduce noise, improving lesion identification
      without affecting the image resolution, allowing SPECT studies with reduced count
      statistic. This allows for either half-time (HT) or half-dose (HD) cardiac SPECT,
      with image quality and quantitative data comparable to standard-time (ST) or
      standard-dose (SD) SPECT. Few data exist on the comparison between conventional
      filtered backprojection (FBP) and this new algorithm in a clinical setting. The
      aim of this study was to compare the performance of FBP and WBRTM. METHODS:
      Phantoms studies were performed to compare spatial resolution and contrast
      recovery with FBP, ordered subset expectation maximization (OSEM) and WBRTM. A
      group of 92 patients, with different cardiac pathology, scheduled for a stress
      rest SPECT were studied: 52 patients (group A) were injected with a SD of tracer
      and underwent both ST and HT SPECT; 40 patients (group B) were injected with a
      half dose of tracer and underwent ST SPECT and immediately after an additional
      SPECT at double time/projection (DT), to compensate for the low count statistic.
      A 2-day (99m)Tc-sestamibi protocol was used in all patients. SD/ST and HD/DT
      SPECT were reconstructed with a conventional FBP; SD/HT and HD/ST SPECT were
      reconstructed with WBRTM. The summed stress score (SSS) and summed rest score
      (SRS) were calculated; the left ventricular ejection fraction (LVEF) was
      automatically derived. RESULTS: In group A (SD), no significant differences were
      observed between ST FBP SPECT and HT WBRTM in SSS (11.1 and 11.7, respectively)
      and SRS (9.4 and 10.3, respectively, NS). LVEF on rest acquisitions was also
      comparable (50% on ST SPECT and 49% on HT SPECT, NS); LVEF on post-stress studies
      in HT SPECT (46%) was lower than ST SPECT (50%), although not statistically
      significant. In group B (HD), SSS (6.2 in ST and 5.3 in DT) and SRS (4.0 in ST
      and 3.3 in DT) were also comparable. No differences were documented between ST
      and DT in rest (47 and 48%, respectively) and stress (48 and 50%, respectively)
      LVEF. CONCLUSION: WBRTM performance and image quality were comparable to those of
      conventional FBP, allowing for either HT or HD studies. The former allows for an
      increased patient throughput and optimization of resources. The latter modalities
      would allow for a significant reduction in both patients' and operators'
      exposure. Further studies are needed to validate the clinical use of this method.

PMID- 21069318
TI  - Optimal specific radioactivity of anti-HER2 Affibody molecules enables
      discrimination between xenografts with high and low HER2 expression levels.
AB  - PURPOSE: Overexpression of the HER2 receptor is a biomarker for predicting those
      patients who may benefit from trastuzumab therapy. Radiolabelled Affibody
      molecules can be used to visualize HER2 expression in tumour xenografts with high
      sensitivity. However, previous studies demonstrated that the difference in uptake
      in xenografts with high and low HER2 expression levels is not proportional to the
      difference in expression levels. We hypothesized that discrimination between
      tumours with high and low HER2 expression may be improved by increasing the
      injected dose (reducing the specific activity) of the tracer. METHODS: The
      influence of injected dose of anti-HER2 (111)In-DOTA-Z(HER2 342) Affibody
      molecule on uptake in SKOV-3 (high HER2 expression) and LS174T (low expression)
      xenografts was investigated. The optimal range of injected doses enabling
      discrimination between xenografts with high and low expression was determined. To
      verify this, tumour uptake was measured in mice carrying both SKOV-3 and LS174T
      xenografts after injection of either 1 or 15 MUg (111)In-DOTA-Z(HER2:342).
      RESULTS: An increase in the injected dose caused a linear decrease in the
      radioactivity accumulation in the LS174T xenografts (low HER2 expression). For
      SKOV-3 xenografts, the dependence of the tumour uptake on the injected dose was
      less dramatic. The injection of 10-30 MUg (111)In-DOTA-Z(HER2:342) per mouse led
      to the largest difference in uptake between the two types of tumour. Experiments
      in mice bearing two xenografts confirmed that the optimized injected dose enabled
      better discrimination of expression levels. CONCLUSION: Careful optimization of
      the injected dose of Affibody molecules is required for maximum discrimination
      between xenografts with high and low levels of HER2 expression. This information
      has potential relevance for clinical imaging applications.

PMID- 21069319
TI  - Decreased cerebral alpha4beta2* nicotinic acetylcholine receptor availability in
      patients with mild cognitive impairment and Alzheimer's disease assessed with
      positron emission tomography.
AB  - PURPOSE: Postmortem studies indicate a loss of nicotinic acetylcholine receptor
      (nAChRs) in Alzheimer's disease (AD). In order to establish whether these changes
      in the cholinergic system occur at an early stage of AD, we carried out positron
      emission tomography (PET) with a specific radioligand for the alpha4beta2*
      nicotinic acetylcholine receptor (alpha4beta2* nAChR) in patients with mild to
      moderate AD and in patients with amnestic mild cognitive impairment (MCI), who
      have a high risk to progress to AD. METHODS: Nine patients with moderate AD,
      eight patients with MCI and seven age-matched healthy controls underwent 2
      [(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA-85380) PET. After
      coregistration with individual magnetic resonance imaging the binding potential
      (BP(ND)) of 2-[(18)F]FA-85380 was calculated using either the corpus callosum or
      the cerebellum as reference regions. PET data were analysed by region of interest
      analysis and by voxel-based analysis. RESULTS: Both patients with AD and MCI
      showed a significant reduction in 2-[(18)F]FA-85380 BP(ND) in typical AD-affected
      brain regions. Thereby, the corpus callosum was identified as the most suitable
      reference region. The 2-[(18)F]FA-85380 BP(ND) correlated with the severity of
      cognitive impairment. Only MCI patients that converted to AD in the later course
      (n = 5) had a reduction in 2-[(18)F]FA-85380 BP(ND). CONCLUSION: 2-[(18)F]FA
      85380 PET appears to be a sensitive and feasible tool for the detection of a
      reduction in alpha4beta2* nAChRs which seems to be an early event in AD. In
      addition, 2-[(18)F]FA-85380 PET might give prognostic information about a
      conversion from MCI to AD.

PMID- 21069320
TI  - Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid
      scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy.
AB  - PURPOSE: We previously reported in a small series of patients that (99m)Tc-3,3
      diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy tested
      positive in transthyretin-related (TTR) (both mutant and wild-type) but not in
      primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger
      cohort of patients with AC. METHODS: We evaluated (1) 45 patients with TTR
      related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non
      affected controls. Myocardial uptake of (99m)Tc-DPD (740 MBq i.v.) was
      semiquantitatively and visually assessed at 5 min and at 3 h. RESULTS: Heart
      retention (HR) and heart to whole-body retention ratio (H/WB) of late (99m)Tc-DPD
      uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both
      unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%;
      H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative
      predictive accuracy of visual scoring of cardiac retention were: 80 and 100%
      (visual score >=1); 88 and 100% (visual score >=2); and 100 and 68% (visual score
      = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the
      only positive predictor of increasing (99m)Tc-DPD uptake in terms of both HR
      [beta 2.5, 95% confidence interval (CI) 1.5-3.5; p < 0.0001] and H/WB (beta 3.5,
      95% CI 2.1-4.9; p < 0.0001). CONCLUSION: While (99m)Tc-DPD scintigraphy was
      confirmed to be useful for differentiating TTR from AL-related AC, diagnostic
      accuracy was lower than previously reported due to a mild degree of tracer uptake
      in about one third of AL patients. (99m)Tc-DPD scintigraphy can provide an
      accurate differential diagnosis in cases of absent or intense uptake evaluated by
      visual score.

PMID- 21069321
TI  - Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of
      advanced melanoma patients can lead to long-term clinical responses independent
      of the peptide used.
AB  - Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients.
      Several strategies have been employed to load DC with antigen, including peptide
      loading. To increase immunogenicity of peptides, major histocompatibility complex
      (MHC) class I binding affinity and stability of peptide-MHC complexes at the cell
      surface may be improved by modification of the amino acid sequence. In this
      study, we compared the capacity of DC loaded with wild-type versus modified gp100
      peptides with higher binding affinities to induce an immune and clinical response
      in advanced melanoma patients. Metastatic HLA-A2.1(+) melanoma patients were
      vaccinated intravenously (on average 25 * 10(6) DC) and intradermally (on average
      11 * 10(6) DC) with mature DC loaded with keyhole limpet hemocyanin (KLH)
      together with tyrosinase peptide and either wild-type (15 patients) or modified
      (12 patients) gp100 peptides. All vaccinated patients showed a pronounced
      proliferative T cell or humoral response against KLH. Gp100-specific T cell
      responses were monitored in post-treatment delayed type hypersensitivity (DTH)
      skin biopsies by tetramer and functional analysis. Antigen-specific T cells were
      found in 2 of 15 patients vaccinated with wild-type gp100-loaded DC, versus 1 of
      12 patients vaccinated with modified peptide-loaded DC. These three patients also
      had the best clinical response, with long-term (>8 years) complete responses in
      two patients, one in each group. We conclude that vaccination with peptide-loaded
      DC can result in long-term clinical responses in a minority of metastatic
      melanoma patients, and that the use of modified as compared to wild-type gp100
      peptides for DC loading does not result in a relevant enhanced immune responses.

PMID- 21069323
TI  - An autologous dendritic cell canine mammary tumor hybrid-cell fusion vaccine.
AB  - Mammary cancer is among the most prevalent canine tumors and frequently resulting
      in death due to metastatic disease that is highly homologous to human breast
      cancer. Most canine tumors fail to raise effective immune reactions yet, some
      spontaneous remissions do occur. Hybrid canine dendritic cell-tumor cell fusion
      vaccines were designed to enhance antigen presentation and tumor immune
      recognition. Peripheral blood-derived autologous dendritic cell enriched
      populations were isolated from dogs based on CD11c(+) expression and fused with
      canine mammary tumor (CMT) cells for vaccination of laboratory Beagles. These
      hybrid cells were injected into popliteal lymph nodes of normal dogs, guided by
      ultrasound, and included CpG-oligonucleotide adjuvants. Three rounds of
      vaccination were delivered. Significant IgG responses were observed in all
      vaccinated dogs compared to vehicle-injected controls. Canine IgG antibodies
      recognized shared CMT antigens as was demonstrated by IgG-recognition of three
      unrelated/independently derived CMT cell lines, and recognition of freshly
      isolated, unrelated, primary biopsy-derived CMT cells. A bias toward an IgG2
      isotype response was observed after two vaccinations in most dogs. Neither
      significant cytotoxic T cell responses were detected, nor adverse or side-effects
      due to vaccination or due to the induced immune responses noted. These data
      provide proof-of-principle for this cancer vaccine strategy and demonstrate the
      presence of shared CMT antigens that promote immune recognition of mammary
      cancer.

PMID- 21069322
TI  - A phase II study of the cancer vaccine TG4010 alone and in combination with
      cytokines in patients with metastatic renal clear-cell carcinoma: clinical and
      immunological findings.
AB  - MUC1 over-expression in renal clear-cell carcinoma (RCC) is associated with poor
      prognosis. This phase II study determined the efficacy and tolerability of
      TG4010, a cancer vaccine based on a modified vaccinia virus expressing MUC1 and
      interleukin-2, in combination with cytokines, as first-line therapy in metastatic
      RCC. Thirty-seven patients with progressive, MUC1-positive RCC received TG4010
      10(8) pfu/inj weekly for 6 weeks, then every 3 weeks until progression, when
      TG4010 was continued in combination with interferon-alpha2a and interleukin-2.
      Assessments included clinical response (primary endpoint), safety, time to
      treatment failure (TTF), overall survival (OS), and immune response. No objective
      clinical responses occurred. Five of the 27 evaluable patients (18%) had stable
      disease for >6 months with TG4010 alone and six of 20 patients (30%) had stable
      disease for >6 months with TG4010 plus cytokines. Median TTF was 4.1, 3.6, and
      9.3 months for monotherapy, combination therapy, and overall, respectively.
      Median OS was 19.3 months for all patients and 22.4 months combination therapy
      recipients. The most frequent TG4010-related adverse events were minor-to
      moderate injection-site reactions, fatigue, and flu-like symptoms. Six of 28
      patients showed a MUC1 CD4+ T cell proliferative response during therapy. Anti
      MUC1 CD8+ T cells were detected before and after therapy in 3 and 4 patients,
      respectively. MUC1-specific CD8+ T cell responses were associated with longer
      survival. Therapy with TG4010 plus cytokines appears to be feasible and well
      tolerated in patients with metastatic RCC. However, these data should be
      interpreted with caution, as additional prospective studies are necessary to
      clarify the clinical efficacy of this therapy.

PMID- 21069324
TI  - Effects of a new centrifugation method on adipose cell viability for autologous
      fat grafting.
AB  - The use of adipose tissue transfer in plastic and reconstructive surgery is not
      new and has been studied extensively. Due to different results with regard to
      adipose cell damage and the level of survival of the transferred tissue in
      clinical practice, the authors aimed to investigate the effects of centrifugation
      on fat aspirates to optimize the centrifugal force for fat transplantation and to
      obtain an increased number of intact adipose progenitor cells. The following
      different centrifugation forces were evaluated in vitro in terms of fat
      decantation: 3,000 rpm (1,500*g), 1,300 rpm (250*g), and 500 rpm (50*g).
      Moreover, the density level, morphology of fat cells, cell viability, and
      progenitor cell number also were evaluated. Centrifugation leads to a good fat
      tissue density, with a significant number of progenitor cells, and efficiently
      removes the liquid portion. High centrifugal forces (at 3,000 rpm) caused
      significant damage to fat cells with low cell viability, whereas very low
      centrifugal forces (at 500 rpm) showed little effect on adipose tissue density,
      resembling fat decantation. Fat aspirates, withdrawn from 30 healthy donors in
      vivo, were centrifuged at different rotations per minute (rpm), as follows. For
      the 10 patients in group A, Coleman's technique was used with a centrifugation of
      the aspirated fat at 3,000 rpm (1,500*g) for 3 min. For the 10 patients in group
      B, the authors' technique was used, with centrifugation of the aspirated fat at
      1,300 rpm (250*g) for 5 min. For the 10 patients in group C, simple decantation
      of fat was used. In conclusion, a centrifugal force of 1,300 rpm resulted in
      better density of adipose tissue, with good cell viability and increased ability
      to preserve a significant number of progenitor cells.

PMID- 21069325
TI  - Percutaneous treatment of biliary cast syndrome after orthotopic liver
      transplantation: comparison of mechanical versus hydraulic rheolytic cast
      extraction.
AB  - PURPOSE: Biliary cast syndrome (BCS) is the presence of casts within the
      intrahepatic or extrahepatic biliary system after orthotopic liver
      transplantation. Our work compares two percutaneous methods for BCS treatment:
      the mechanical cast-extraction technique (MCE) versus the hydraulic cast
      extraction (HCE) technique using a rheolytic system. MATERIALS AND METHODS: A
      total of 24 patients were included in the study. Six patients were referred for
      HCE, and 18 patients were treated with MCE. A statistically significant larger
      number of sessions was required in the MCE group (21.0, range 11 to 72 sessions)
      (p = 0.033). RESULTS: Median therapy duration was shorter in the HCE group at 2.4
      months (range 2 to 5) compared with 6.7 months (range 3 to 39) in the MCE group
      (p < 0.001). Both patient acceptance was better and costs for total therapy were
      40% less in the HCE group. No significant differences where found concerning
      clinical and biochemical improvement or graft and patient survival. CONCLUSION:
      The use of the hydraulic rheolytic system decreased total therapy time, thereby
      decreasing the induced inflammation time of the biliary tree. A significant
      benefit of HCE has been observed in our patients when we compare our results with
      those of MCE.

PMID- 21069326
TI  - Carotid stenting for restenosis after endarterectomy.
AB  - INTRODUCTION: Restenosis after carotid endarterectomy (CEA) has been described in
      8-19% of patients, 14-23% of whom become symptomatic. This study analyzes our
      experience with carotid artery stenting (CAS) for post-CEA recurrent stenoses.
      METHOD: Retrospective database and case-note review. RESULTS: Between January
      2000 and September 2008, a total of 27 patients (15 symptomatic) with
      hemodynamically significant internal carotid artery post-CEA restenosis underwent
      CAS. Median stenosis of target vessels was 90% (range 75-95%). There was one
      periprocedural death (3.7%); no others occurred during the median 34-month follow
      up (range 0.1-84 months). There was one late transient ischemic attack 12 months
      after CAS that was not associated with in-stent restenosis. One 90% restenosis
      and one occlusion were detected during follow-up at 38 and 57 months after CAS.
      The remaining patients had no evidence of further restenosis and remained free
      from cerebrovascular symptoms. CONCLUSION: CAS offers a feasible option for the
      management of carefully selected patients with symptomatic and asymptomatic
      restenosis after CEA.

PMID- 21069328
TI  - Embolization of hepatic arteriovenous shunt with absolute ethanol in a patient
      with hepatocellular carcinoma.
AB  - We report a 76-year-old man who had hepatocellular carcinoma (HCC) with
      arteriovenous shunting (AVS). Transcatheter chemoembolization (TACE) was selected
      as treatment because of poor pulmonary function. To prevent pulmonary embolism
      caused by the flow of embolic materials through the AVS, we performed
      embolization of the AVS with absolute ethanol under flow control by balloon
      catheters. Subsequently, we could perform TACE for HCC safely.

PMID- 21069327
TI  - Lipoproteins and the development of restenosis after stent implantation in the
      superficial femoral artery in patients with peripheral artery disease.
AB  - PURPOSE: High levels of apolipoprotein B (apo B) are a risk factor for the
      development of major vascular events. We evaluated the association between plasma
      lipoproteins and the development of superficial femoral artery (SFA) in-stent
      restenosis and reocclusion in patients with peripheral artery disease. MATERIALS
      AND METHODS: We included 139 patients with SFA stenting. Plasma lipoproteins were
      measured after stent implantation. Stent restenosis was assessed with duplex scan
      after 3, 6, and 12 months. A stenosis grade was considered relevant if >50%.
      RESULTS: Seventy-two patients experienced recurrence of their atherosclerotic
      disease, meaning restenosis of >50% within 1 year of follow-up. Ten of these
      patients had a stent occlusion. In the patients who experienced recurrence, the
      mean apo B level was 105.8 versus 94.9 mg/dl in patients without recurrence (P <
      0.05). Patients without recurrence had higher high-density lipoprotein
      cholesterol levels than patients with recurrence (39.7 vs. 34.7 mg/dl, P < 0.05).
      Comparing patients with a stent occlusion (n = 10) and those with a restenosis of
      75-99% (n = 28), the patients with a stent occlusion had higher levels of plasma
      cholesterol (234.1 vs. 185.9 mg/dl, P < 0.05), apo B (135.3 vs. 99.8 mg/dl, P <
      0.05), low-density lipoprotein cholesterol (160.3 vs. 113.6 mg/dl, P < 0.05), and
      low-density lipoprotein apo B (115.5 vs. 82.4 mg/dl, P < 0.001) than the patients
      with restenosis of 75-99% (n = 28). CONCLUSION: Changes in the lipid profile
      could be one reason for the development of restenosis and for the development of
      reocclusion after SFA stenting.

PMID- 21069329
TI  - A novel mechanical thrombectomy device for retrieval of intravascular thrombus.
AB  - PURPOSE: Thrombotic and embolic vascular occlusion represents a leading cause of
      morbidity and mortality. Currently available thrombectomy devices have
      limitations, including difficulty removing organized thrombus and clot
      fragmentation with distal embolization. A novel mechanical thrombectomy device
      (MTD), designed to remove both hard and soft thrombus without trauma to the blood
      vessel, was tested in preclinical porcine models evaluating efficacy, safety, and
      ease of use. MATERIALS AND METHODS: A total of 26 vessels in 14 pigs underwent
      mechanical thrombectomy with MTD. Thrombectomy was performed in nine superficial
      femoral arteries, eight subclavian arteries, five primary branches of the
      subclavian artery, lateral thoracic artery or the thyrocervical trunk, and four
      external carotids. Subacute organized fibrin-laden thrombus was injected into the
      arteries producing vascular occlusion. The MTD was then used for thrombectomy to
      restore patency and blood flow. RESULTS: Intact thrombus was retrieved from 24 of
      26 of the vessels with a single pass of the MTD, resulting in complete
      restoration of patency in 21 vessels and partial patency in 4 vessels. In 8 cases
      that used an early design, the embolic material fragmented during withdrawal from
      the access sheath. In 4 procedures that used an early design, the MTD failed to
      deploy fully and the embolus was not completely captured. No intraprocedural
      complications or vascular damage occurred. CONCLUSIONS: The present pilot studies
      demonstrate basic safety and efficacy of a novel MTD with design attributes
      suitable for retrieval of intact acute and organized chronic thrombus. The device
      has potential intracranial and peripheral utility.

PMID- 21069330
TI  - Minimally invasive mechanical thrombectomy: salvage of a renal transplant after
      pelvicaliceal clot retention.

PMID- 21069331
TI  - Use of PTFE stent grafts for hemodialysis-related central venous occlusions:
      intermediate-term results.
AB  - PURPOSE: To assess the safety and effectiveness of a polytetrafluoroethylene
      (PTFE) encapsulated nitinol stents (Bard Peripheral Vascular, Tempe, AZ) for
      treatment of hemodialysis-related central venous occlusions. MATERIALS AND
      METHODS: Study design was a single-center nonrandomized retrospective cohort of
      patients from May 2004 to August 2009 for a total of 64 months. There were 14
      patients (mean age 60 years, range 50-83 years; 13 male, 1 female). All patients
      had autogenous fistulas. All 14 patients had central venous occlusions and
      presented with clinical symptoms of the following: extremity swelling (14%, 2 of
      14), extremity and face swelling (72%, 10 of 14), and face swelling/edema (14%, 2
      of 14). There was evidence of access dysfunction with decreased access flow in
      36% (5 of 14) patients. There were prior interventions or previous line placement
      at the site of the central venous lesion in all 14 patients. Results were
      assessed by recurrence of clinical symptoms and function of the access circuit
      (National Kidney Foundation recommended criteria). RESULTS: Sixteen consecutive
      straight stent grafts were implanted in 14 patients. Average treated lesion
      length was 5.0 cm (range, 0.9-7 cm). All 14 patients had complete central venous
      occlusion (100% stenosis). The central venous occlusions were located as follows:
      right subclavian and brachiocephalic vein (21%, 3 of 14), right brachiocephalic
      vein (36%, 5 of 14), left brachiocephalic vein (36%, 5 of 14), and bilateral
      brachiocephalic vein (7%, 1 of 14). A total of 16 PTFE stent grafts were placed.
      Ten- or 12-mm-diameter PTFE stent grafts were placed. The average stent length
      was 6.1 cm (range, 4-8 cm). Technical (deployment), anatomic (<30% residual
      stenosis), clinical (resolution of symptoms), and hemodynamic (resolution of
      access dysfunction) success were 100%. At 3, 6, and 9 months, primary patency of
      the treated area and access circuit were 100% (14 of 14). CONCLUSIONS: This PTFE
      encapsulated stent graft demonstrates encouraging intermediate-term patency
      results for central vein occlusions. Further prospective studies with long-term
      assessment and larger patient populations will be required.

PMID- 21069332
TI  - Changes in dose-area product, entrance surface dose, and lens dose to the
      radiologist in a vascular interventional laboratory when an old X-ray system is
      exchanged with a new system.
AB  - PURPOSE: The aim of this study was to compare dose-area product (DAP), entrance
      surface dose (ESD), and lens dose to radiologists for an old and a new X-ray
      system in a vascular interventional laboratory. MATERIALS AND METHODS: DAP, ESD,
      fluoroscopy time, number of images, and patient weight were recorded for patients
      undergoing the following four procedures: percutaneous transluminal angioplasty
      (PTA) and stenting (divided into two subgroups, lower extremities and pelvis),
      nephrostomy, and treatment for varicocele. Halfway through the registration
      period, the 9-year-old X-ray equipment was exchanged with a new system. Lens
      doses to the radiologist were measured. RESULTS: There was a reduction in DAP for
      all procedures: PTA lower extremities 31% (12-8 Gy cm(2)), PTA/stenting pelvis
      67% (134-44 Gy cm(2)), nephrostomy 39% (7-4 Gy cm(2)), and varicocele 70% (37-11
      Gy cm(2)). The reduction in number of images was 17% (158-131), 23% (153-118),
      68% (2-1), and 31% (50-35), explaining a part of the dose reduction. The
      reduction in ESD was 33, 60, 38, and 46%. The differences in measured lens doses
      indicate a dose reduction in three procedures (19-53%) and an increase in one
      (56%), but differences are not statistically significant. CONCLUSION: DAP and ESD
      from the X-ray system were reduced for all procedures. The reduction was greater
      in the more radiation-demanding procedures.

PMID- 21069334
TI  - Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin:
      potential for consolidation in ovarian cancer.
AB  - PURPOSE: Most ovarian cancers recur after first-line treatment. We studied the
      pharmacology, tolerability, and therapeutic potential of intraperitoneal (IP)
      topotecan, alone and with IP cisplatin. METHODS: Patients received IP topotecan
      1.5 mg (flat dose) daily on days 1-5 (level 0) via IP catheter. Subsequent
      cohorts received IP cisplatin 50 mg/m(2) on day 1 added to topotecan 1.5 mg on
      days 1-3 (level I), topotecan 1.25 mg on days 1-3 (level II), or topotecan 1.25
      mg on days 1-5 (level III). Plasma and IP concentrations of total and lactone (E
      ring closed) topotecan were measured on days 1 and 2 in cycles 1 and 2. RESULTS:
      Sixteen patients (15 tubo-ovarian, 1 gastric cancers) were entered at levels 0
      (3), I (4), II (4), or III (5). Dose-limiting neutropenias occurred in seven
      patients at dose levels I and III; grade 3 thrombocytopenia occurred in two at
      level III. Other toxicities included grade 1 hives in two, serum creatinine
      elevations in two, and Staphylococcus epidermidis and chemical peritonitis (one
      each). A median progression-free survival of 13 months was recorded among ovarian
      cancer patients who had minimal (6) or no residuum (3) after platinum-based
      induction; 5 are alive at 4 years. Topotecan's AUC IP/AUC plasma ratios ranged
      from 13 to 119. CONCLUSION: Topotecan IP for 3-5 days is tolerable; occasionally,
      myelosuppression is dose-limiting. Topotecan 1.25 mg (days 1-3) with IP cisplatin
      50 mg/m(2) (day 1) is a regimen suitable for consolidation in phase 3 trials.

PMID- 21069333
TI  - Transcatheter arterial chemoembolization for liver cancer: is it time to
      distinguish conventional from drug-eluting chemoembolization?
AB  - Conventional transcatheter arterial chemoembolization and chemoembolization with
      drug-eluting beads are increasingly being performed interchangeably in many
      institutions throughout the world. As both therapies continue to being tested in
      many phase II and III studies and in combination with other therapies, especially
      targeted agents, for treatment of primary and metastatic liver cancer, it is
      imperative to review their current status and evaluate their impact on patient
      survival. This review critically assesses patient selection, indications,
      contraindications, techniques, materials, safety, and clinical outcomes of
      patients treated with conventional chemoembolization and chemoembolization with
      drug-eluting beads.

PMID- 21069335
TI  - A dose-escalation study of pemetrexed and docetaxel in non-small-cell lung
      cancer.
AB  - A phase I study was conducted to determine the maximum tolerated doses (MTD) and
      the dose-limiting toxicities (DLT) of pemetrexed and docetaxel in patients with
      advanced unresectable or metastatic non-small-cell lung cancer (NSCLC). Patients
      were treated with escalating doses of pemetrexed (400-600 mg/m(2) as a 10-min
      intravenous infusion) and docetaxel (65-85 mg/m(2) as a 1-h intravenous infusion)
      on day 1, every 3 weeks. An expanded accrual at the level of the recommended dose
      (RD) had been scheduled. Forty-two patients with metastatic NSCLC were enrolled
      in the phase I study and 20 additional patients at the RD level. The MTD could
      not be reached even at the doses of 550 and 85 mg/m(2) for pemetrexed and
      docetaxel, respectively, which are higher than the recommended dose for each drug
      given as a single agent. Therefore, the RD was defined at 500 mg/m(2) pemetrexed
      and 75 mg/m(2) docetaxel. Among the 164 administered chemotherapy cycles (phase I
      part), there were three episodes of febrile neutropenia whereas 13 (7.9%) and 11
      (6.7%) cycles were complicated with grade III and IV neutropenia, respectively.
      Three patients developed grade III/IV thrombocytopenia. Non-hematologic toxicity
      was mild with grade III fatigue occurring in three (6.7%) patients. There was no
      toxic death. The favorable toxicity profile of the regimen was confirmed in
      patients treated at the RD level. Overall, one complete (CR) and 13 partial
      responses (PR) (overall response rate = 23; 95% C.I:12.4-33.5%] were documented.
      The combination of pemetrexed and docetaxel seems to be an effective regimen in
      NSCLC with acceptable and manageable toxicity, which merits further
      investigation.

PMID- 21069337
TI  - Prediction of human pharmacokinetics and tissue distribution of apicidin, a
      potent histone deacetylase inhibitor, by physiologically based pharmacokinetic
      modeling.
AB  - PURPOSE: The objectives of this study were to develop physiologically based
      models for the pharmacokinetics (PK) and organ distribution of apicidin in rats
      and mice and to predict human PK in blood and organs. METHODS: The PK of apicidin
      was characterized in rats and mice after i.v. bolus injection, and distribution
      to various tissues was determined in rats following i.v. infusions at steady
      state. The developed models were prospectively validated within rat and within
      mouse and by scaling from rat to mouse using data after multiple i.v. injections.
      Human PK was predicted by the physiologically based modeling using intrinsic
      clearance data for humans from in vitro experiments. RESULTS: The Cl(s) predicted
      for human (9.8 ml/min/kg) was lower than those found in mice (116.9 ml/min/kg)
      and rats (61.6 ml/min/kg), and the V(ss) predicted for human (1.9 l/kg) was less
      than in mice (2.0 l/kg) and rats (2.5 l/kg). Consequently, the predicted t (1/2)
      was longer in human (2.3 h) than in mice and rats (0.4 and 0.9 h, respectively).
      The highest concentrations of apicidin were predicted in liver followed by
      adipose tissue, kidney, lung, spleen, heart, arterial blood, venous blood, small
      intestine, stomach, muscle, testis, and brain. CONCLUSIONS: The developed models
      adequately described the PK of apicidin in rats and mice and were applied to
      predict human PK. These models may be useful in predicting human blood and tissue
      concentrations of apicidin under different exposure conditions.

PMID- 21069336
TI  - Improved antiangiogenic and antitumour activity of the combination of the natural
      flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice.
AB  - PURPOSE: The natural flavonoid fisetin was recently identified as a lead compound
      that stabilizes endothelial cell microtubules. In this study, we investigated the
      antiproliferative and antiangiogenic properties of fisetin in vitro and in vivo.
      METHODS: Fisetin cytotoxicity was evaluated using Lewis lung carcinoma cells
      (LLC), endothelial cells and NIH 3T3 cells. Endothelial cell (EC) migration and
      capillary-like structure formation were evaluated using EAhy 926 cells. In vivo
      tumour growth inhibition studies were performed using LLC-bearing mice treated
      with fisetin and/or cyclophosphamide (CPA). RESULTS: The fisetin IC(50) was 59
      MUM for LLC and 77 MUM for EC cells, compared to 210 MUM for normal NIH 3T3 cells
      (24 h). Fisetin inhibited EC migration and capillary-like structure formation at
      non-cytotoxic concentrations (22-44 MUM). In mice, fisetin inhibited angiogenesis
      assessed using the Matrigel plug assay. In LLC-bearing mice, fisetin produced a
      67% tumour growth inhibition (223 mg/kg, intraperitoneal), similar to the 66%
      produced by low-dose CPA (30 mg/kg, subcutaneous). When fisetin and CPA were
      combined, however, a marked improvement in antitumour activity was observed (92%
      tumour growth inhibition), with low systemic toxicity. Tumour histology showed
      decreased microvessel density with either fisetin or CPA alone, and a dramatic
      decrease after the fisetin/CPA combination. CONCLUSIONS: We have shown that
      fisetin not only displays in vitro and in vivo antiangiogenic properties, but
      also can markedly improve the in vivo antitumour effect of CPA. We propose that
      this drug combination associating a non-toxic dietary flavonoid with a cytotoxic
      agent could advantageously be used in the treatment of solid tumours.

PMID- 21069338
TI  - Antitumor agent PX-12 inhibits HIF-1alpha protein levels through an Nrf2/PMF-1
      mediated increase in spermidine/spermine acetyl transferase.
AB  - PURPOSE: Thioredoxin-1 (Trx-1) redox signaling regulates multiple aspects of cell
      growth and survival, and elevated tumor levels of Trx-1 have been associated with
      decreased patient survival. PX-12, an inhibitor of Trx-1 currently in clinical
      development, has been found to decrease tumor levels of the HIF-1alpha
      transcription factor. SSAT1 has been reported to bind to HIF-1alpha and RACK1,
      resulting in oxygen-independent HIF-1 ubiquitination and degradation. SSAT2, a
      related protein, stabilizes the interaction of the VHL protein and elongin C with
      HIF-1 leading to oxygen-dependent HIF-1alpha ubiquitination and degradation. We
      investigated the effects of PX-12 and Trx-1 on SSAT1, SSAT2, and inhibition of
      HIF-1alpha. METHODS: A panel of cell lines was treated with PX-12 to investigate
      its effects on SSAT1 and SSAT2 expression, and on HIF-1alpha protein levels. We
      also evaluated the regulation of SSAT1 through the Nrf2 and PMF-1, two trans
      acting transcription factors. RESULTS: We found that PX-12 increased nuclear Nrf2
      activity and antioxidant response element binding. PX-12 also increased the
      expression of SSAT1 but not SSAT2 in a PMF-1-dependent manner that was
      independent of Trx-1. Inhibition of Nrf2 or PMF-1 prevented the increase in SSAT1
      caused by PX-12. CONCLUSIONS: The results show that PX-12, acting independently
      of Trx-1, increases nuclear Nrf2, which interacts with PMF-1 to increase the
      expression of SSAT1. The degradation of HIF-1alpha that results from binding with
      SSAT1 may explain the decrease in HIF-1alpha caused by PX-12 and could contribute
      to the antitumor activity of PX-12.

PMID- 21069339
TI  - The uptake of paclitaxel and docetaxel into ex vivo porcine bladder tissue from
      polymeric micelle formulations.
AB  - Superficial bladder cancer occurs in the urothelial layer of the bladder and is
      usually treated by transurethral resection and chemotherapy. Although the bladder
      is well suited for intravesical chemotherapy, effective drug delivery is
      restricted by urine dilution and poor drug uptake by bladder tissues during a 2 h
      instillation. In this study, freshly excised pig bladder sections were mounted on
      Franz diffusion cells and treated with anticancer drugs paclitaxel (PTX) and
      docetaxel (DTX) formulated in diblock copolymer (methoxy poly(ethylene glycol)
      block-poly (D,L-lactic acid) (MePEG-PDLLA) and methoxy poly(ethylene glycol)
      block-poly(caprolactone) (MePEG-PCL) nanoparticles for 2 h. The bladder sections
      were then frozen, cryosectioned (60-MUm sections) and the amount of (3)H drug
      taken up into each section was determined using liquid scintillation counting.
      Tissue concentration versus tissue depth profiles were obtained for all drug
      formulations and drug exposure obtained from area-under-the-curve (AUC)
      calculations. PTX or DTX loaded in MePEG-PDLLA micelles produced significantly
      higher urothelial tissue levels and greater bladder wall exposures compared to
      their commercial formulations, Cremophor EL/ethanol (PTX) or Tween 80 (DTX). The
      results of this study support the use of diblock copolymer micellar PTX or DTX
      formulations as they allow for improved drug penetration of bladder tissues
      compared to commercial formulations for taxane delivery to superficial bladder
      tumors.

PMID- 21069341
TI  - Clinical benefit of early phase clinical trial participation for advanced sarcoma
      patients.
AB  - PURPOSE: Standard systemic treatment options for patients with advanced sarcoma
      are limited. Depending on the histological subtype, patients receive differing
      lines of therapy usually consisting of doxorubicin, ifosfamide and/or
      trabectedin. After progression on conventional therapies, some patients are
      offered more experimental options including Phase I clinical trials. The aim of
      this study was to evaluate the clinical benefit for sarcoma patients treated
      within the Phase I Unit of a single referral centre. METHODS: The response,
      toxicity and outcome of sarcoma patients treated within Phase I clinical trials
      at the Royal Marsden between August 1998 and December 2010 were analysed.
      RESULTS: One hundred and thirty-three patients were treated. The median number of
      prior systemic therapies was 3 (range 0-6). The median age of these patients was
      48.0 years (range 12.5-81.9), with a male/female ratio of 71/62. One patient
      (0.8%) achieved a complete response and 2 (1.6%) partial responses. The non
      progression rate at 3 and 6 months was 31.5% (95% CI, 23.4-39.6%) and 11.0% (95%
      CI 5.6-16.5%), respectively. The median progression-free survival was 2.1 months
      (95% CI, 1.7-2.5), and median overall survival was 7.6 months (95% CI, 4.8-10.4).
      Twenty-four (18.0%) patients experienced grade 3 or 4 toxicity, and 16 (12.0%)
      stopped trial treatment due to toxicity. CONCLUSION: Phase I clinical trials
      could be considered a therapeutic option in sarcoma patients with no remaining
      standard treatment due to the low risk of toxicity and the potential for clinical
      benefit.

PMID- 21069340
TI  - Lack of in vivo cross-resistance with 4'-thio-ara-C against drug-resistant murine
      P388 and L1210 leukemias.
AB  - PURPOSE: 4'-Thio-beta-D-arabinofuranosylcytosine (4'-thio-ara-C), which has shown
      a broad spectrum of antitumor activity against human tumor systems in mice and is
      undergoing clinical trials, was evaluated for cross-resistance to seven clinical
      agents in order to identify potentially useful guides for patient selection for
      further clinical trials of 4'-thio-ara-C and possible noncross-resistant drug
      combinations with 4'-thio-ara-C. METHODS: A drug resistance profile for 4'-thio
      ara-C, which was administered intraperitoneally daily for nine consecutive days,
      was obtained using seven drug-resistant P388 and L1210 leukemias that were
      implanted intraperitoneally in mice. RESULTS: Multidrug-resistant P388 leukemias
      (leukemias resistant to doxorubicin, etoposide, or paclitaxel) exhibited no cross
      resistance to 4'-thio-ara-C. Leukemias resistant to camptothecin, cisplatin, and
      5-fluorouracil were also not cross-resistant to 4'-thio-ara-C. Only the leukemia
      resistant to 1-beta-D-arabinofuranosylcytosine was cross-resistant to 4'-thio-ara
      C. CONCLUSIONS: The data suggest that (1) it may be important to exclude or to
      monitor with extra care patients who have previously been treated with 1-beta-D
      arabinofuranosylcytosine and (2) the lack of cross-resistance seen with 4'-thio
      ara-C may contribute to therapeutic synergism when 4'-thio-ara-C is combined with
      other agents.

PMID- 21069342
TI  - Signal intensity in T2' magnetic resonance imaging is related to brain glioma
      grade.
AB  - OBJECTIVES: T2' values reflect the presence of deoxyhaemoglobin related to high
      local oxygen extraction. We assessed the feasibility of T2' imaging to display
      regions with high metabolic activity in brain gliomas. METHODS: MRI was performed
      in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas
      with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*.
      Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25
      patients. Images were visually assessed by two readers and five ROIs were
      evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis
      tests were applied for statistical analysis. RESULTS: Three patients were not
      further evaluated because of artefacts. Mean values of high-grade (III-IV)
      gliomas showed significantly lower T2' values than low-grade (II) gliomas (p <
      0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = 
      0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II
      tumours (r = 0.038; p = 0.875). CONCLUSIONS: High-grade tumours revealed lower
      T2' values, presumably because of higher oxygen consumption in proliferating
      tissue. Our results indicate that T2' imaging can be used as an alternative to
      DSC perfusion in the detection of subtle deviations in tumour metabolism.

PMID- 21069343
TI  - Genetic modifier of mitochondrial superoxide dismutase-deficient mice delays
      heart failure and prolongs survival.
AB  - Mn superoxide dismutase (MnSOD)-deficient mice (Sod2-/-) suffer from
      mitochondrial damage and have various survival times and phenotypic presentations
      that are dependent on the genetic background of the mutant mice. The
      mitochondrial NADPH transhydrogenase (NNT) was identified as a putative genetic
      modifier based on a genome-wide quantitative trait association study on the
      molecular defect of the protein in more severely affected Sod2-/- mice and on the
      biological function of NNT. Hence, Sod2-/- mice on the C57BL/6J (B6J) background
      have the shortest survival time, and the mice are homozygous for the truncated
      Nnt allele (Nnt ( T )). On the other hand, genetic backgrounds that support
      longer survival of Sod2-/- mice all have at least one normal copy of Nnt (Nnt ( W
      )). To confirm the role of NNT in the phenotypic modification of Sod2-/- mice, we
      introduced a normal copy of Nnt allele from a C57BL/6 substrain into B6J-Sod2-/-
      mice and analyzed survival time, cardiac functions, and histopathology of the
      heart. The study results show that the presence of a normal Nnt allele preserves
      cardiac function, delays the onset of heart failure, and extends the survival of
      B6J-Sod2-/- mice to the end of gestation. Postnatal survival, however, is not
      supported. Consequently, the majority of B6J-Sod2-/- mice died within a few hours
      after birth and only a few survived for 5-6 days. The study results suggest that
      NNT is important for normal development and function of fetal hearts and that
      there may be other genetic modifier(s) important for postnatal survival of Sod2-/
      mice.

PMID- 21069344
TI  - Spatial and temporal patterns of c-kit positive cells in embryonic lungs.
AB  - BACKGROUND: It has been reported that the smooth muscles in fetal airways exhibit
      spontaneous phasic contractions throughout gestation. However, the mechanism of
      these spontaneous contractions is unknown. In the bowel wall, interstitial cells
      of Cajal (ICCs), which are derived from c-kit positive precursor cells, play an
      important role as pacemaker cells responsible for the spontaneous, rhythmic
      activity in the smooth muscle cells. In this study, we investigated the spatial
      and temporal expression patterns of c-kit positive cells in the embryonic lung
      and its relationship to the smooth muscle cells surrounding the trachea and the
      bronchus. METHODS: Rat fetuses were removed from timed pregnant dams on embryonic
      days (E) 11.5, 13.5, 15.5, and 17.5. Immunohistochemical studies with anti c-kit
      antibody and anti alpha-SMA antibody were carried out using frozen sections.
      RESULTS: A small number of c-kit positive cells were observed in the mesenchyme
      of the lung bud on day E 11.5. They were markedly increased in number on day E
      13.5. On day E 15.5 and on day E 17.5, strong c-kit expressions were observed on
      the vascular wall and moderate expressions in the mesenchyme. C-kit positive
      cells co-localized with alpha-SMA positive smooth muscle cells surrounding the
      airway epithelium. CONCLUSION: Co-localization of c-kit positive cells and airway
      smooth muscles in the fetal lung suggests that c-kit positive cells may play an
      important role in the spontaneous contractions of fetal airways. C-kit
      expressions in the fetal pulmonary vascular wall suggest that these cells may
      play an important role in vasculogenesis and angiogenesis of the embryonic lung.

PMID- 21069345
TI  - Association of lymphocyte crossmatch and the outcome of intestinal
      transplantation in swine.
AB  - BACKGROUND: The effect of preformed antidonor antibodies have been demonstrated
      in various types of solid organ transplantation. However, the significance of
      anti-donor antibodies in intestinal transplantation remains unclear. The aim of
      this study is to evaluate the impact that the extent of T cell crossmatch has on
      the outcome of swine intestinal transplantation. MATERIALS AND METHODS: All
      studies were performed on outbred domestic male pigs weighing from 15 to 20 kg.
      Intestinal transplantation was performed orthotopically with an exchange of
      grafts between white and black pigs. FK506 was administered intravenously (0.1
      mg/kg per day, POD 0-7) for immunosuppression. A lymphocyte crossmatch test was
      performed using the direct CDC crossmatch. The results were considered positive
      when more than 10% of the donor lymphocytes were killed by the recipient's serum.
      In addition, 0-10, 11-20, 21-30, 31-80 and 81-100% of the killed lymphocytes were
      classified as grade 1, 2, 4, 6 and 8, respectively. RESULT: A total of 34
      intestinal transplantations were performed. All but one case had positive donor
      specific T cell crossmatches. The number of grade 2, 4, 6 and 8 cases was 11, 14,
      6 and 2, respectively. Although there was a tendency towards a decreased survival
      according to the grade, the survival rate was not statistically different among
      each different grade. Moreover, the rates of acute cellular rejection and
      vascular complications were not significantly different among the four grades.
      CONCLUSION: These results suggest that the extent of positive T cell crossmatch
      is not associated with the outcome of swine intestinal transplantation.

PMID- 21069346
TI  - Pre-treatment with N-acetylcysteine upregulates superoxide dismutase 2 and
      catalase genes in cadmium-induced oxidative stress in the chick omphalocele
      model.
AB  - PURPOSE: In the chick embryo, administration of the heavy metal Cadmium (Cd)
      induces omphalocele phenotype. Cd is a potent inhibitor of antioxidant enzymes
      and causes accumulation of reactive oxygen species (ROSs) such as hydrogen
      peroxide. Previous work with the Cd chick model has demonstrated that increased
      levels of MDA, as a marker for oxidative stress, 24 h post Cd treatment (24H) are
      identical in chick embryos exposed to Cd. Furthermore, of the several
      antioxidants assessed, only N-acetylcysteine (NAC) has been shown to reduce MDA
      levels to control values in the Cd-treated chick embryo. However, the molecular
      mechanisms by which NAC acts to maintain oxidative stress in the Cd-induced
      ventral body wall defect chick model remains to be unclear. We designed this
      study to investigate the hypothesis that gene expression levels of antioxidant
      enzymes are downregulated in malformed embryos exposed to Cd compared to controls
      and to determine the effect of pre-treatment with NAC on the expression levels of
      genes encoding antioxidant enzymes. METHODS: After 60 h incubation, chick embryos
      were pre-treated with NAC and exposed to either chick saline or Cd. Chicks were
      then harvested at 24H and divided into five groups: control, Cd group without
      malformation [Cd(-)], Cd group with malformation [Cd(+)], NAC + Cd(-) and NAC +
      Cd(+). Real-time PCR was performed to evaluate the relative mRNA expression
      levels of antioxidant enzymes, including superoxide dismutase (SOD)-1, SOD2,
      catalase (CAT) and glutathione peroxidase (GPX)-4. Differences between five
      groups were tested by Tukey-Kramer post-hoc test following one-way ANOVA.
      Statistical significance was accepted at p < 0.05. Immunohistochemistry was also
      performed to evaluate protein expression. RESULTS: The mRNA expression levels of
      SOD2 and CAT were significantly decreased in Cd(+) as compared to controls,
      whereas there was no significant difference between controls and Cd(-) (p < 0.05
      vs. controls). In addition, gene expression levels of SOD2 and CAT were
      significantly increased in NAC + Cd(-) as compared to Cd(+) and NAC + Cd(+) (p <
      0.05 vs. controls). However, there were no significant differences in the
      expression levels of SOD1 and GPX4 among any groups. Increased immunoreactivity
      of SOD2 and CAT was also observed in NAC + Cd(-) as compared to Cd(+) and NAC +
      Cd(+). CONCLUSION: Our results suggest that SOD2 and CAT may play an important
      role in preventing Cd-induced teratogenesis. Prenatal treatment with drugs which
      can upregulate SOD2 and CAT transcripts may have a therapeutic potential in
      preventing omphalocele phenotype.

PMID- 21069347
TI  - How valuable is ductal plate malformation as a predictor of clinical course in
      postoperative biliary atresia patients?
AB  - PURPOSE: We assessed ductal plate malformation (DPM) as a prognostic factor for
      mid-/long-term outcome in post-hepatoportoenterostomy (HPE) biliary atresia
      patients. METHODS: Of 78 cases of HPE performed between 1989 and 2009, biopsy
      specimens were available for 43. Cytokeratin 19 was used to identify DPM and
      preoperative status, postoperative serum total bilirubin, time taken to become
      jaundice-free, duration of jaundice-free period, steroid usage, incidences of
      cholangitis, bile lakes, and varices, and requirement for reoperation and liver
      transplantation were compared. RESULTS: DPM was detected in 21/43 (48.8%)
      subjects [DPM-positive (DPM+)]. Differences were identified for maximum
      postoperative serum total bilirubin: DPM+ (12.28 +/- 1.00 mg/dL) versus DPM
      negative (DPM-) (9.67 +/- 0.71 mg/dL) (P < 0.05) and total steroid usage: DPM+
      (98.3 +/- 11.8 mg/kg) versus DPM- (83.4 +/- 15.9 mg/kg) (P = NS). However, total
      steroid dose in jaundice-free cases was significantly higher in DPM+ [75.3 +/-
      10.0 mg/kg (n = 14) vs. 48.1 +/- 6.4 mg/kg (n = 19); P < 0.05)]. There were no
      differences for complications. Mean duration of follow-up was significantly
      shorter for DPM+ (60.9 +/- 38.4 vs. 113.8 +/- 56.9 months; P < 0.05). CONCLUSION:
      Postoperative total bilirubin was higher in DPM+ cases, thus higher doses of
      steroids were required. However, DPM+ did not appear to influence the incidence
      of complications mid-/long-term.

PMID- 21069348
TI  - Skingineering II: transplantation of large-scale laboratory-grown skin analogues
      in a new pig model.
AB  - BACKGROUND: Tissue engineering of skin with near-normal anatomy is an intriguing
      novel strategy to attack the still unsolved problem of how to ideally cover
      massive full-thickness skin defects. After successful production of large, pig
      cell-derived skin analogues, we now aim at developing an appropriate large animal
      model for transplantation studies. MATERIALS AND METHODS: In four adult Swiss
      pigs, full-thickness skin defects, measuring 7.5 * 7.5 cm, were surgically
      created and then shielded against the surrounding skin by a new, self-designed
      silicone chamber. In two animals each, Integra dermal regeneration templates or
      cultured autologous skin analogues, respectively, were applied onto the wound
      bed. A sophisticated shock-absorbing dressing was applied for the ensuing 3
      weeks. Results were documented photographically and histologically. RESULTS: All
      animals survived uneventfully. Integra healed in perfectly, while the dermo
      epidermal skin analogues showed complete take of the dermal compartment but spots
      of missing epidermis. The chamber proved effective in precluding ("false
      positive") healing from the wound edges and the special dressing efficiently kept
      the operation site intact and clean for the planned 3 weeks. CONCLUSION: We
      present a novel and valid pig model permitting both transplantation of large
      autologous, laboratory-engineered skin analogues and also keeping the site of
      intervention undisturbed for at least three postoperative weeks. Hence, the model
      will be used for experiments testing whether such large skin analogues can
      restore near-normal skin, particularly in the long term. If so, clinical
      application can be envisioned.

PMID- 21069349
TI  - Microscopic magnetic resonance imaging of the thoracic venous system in rats with
      congenital diaphragmatic hernia.
AB  - BACKGROUND/AIM: Infants and rats with congenital diaphragmatic hernia (CDH) have
      malformations of the heart and the great arteries caused by neural crest (NC)
      dysregulation during embryogenesis. Abnormally narrow jugular veins have been
      found in babies during cannulation for ECMO. However, the venous system has not
      been examined in depth so far. We hypothesized that abnormal patterning and/or
      size of the thoracic veins could occur in rats with CDH. This hypothesis was
      tested by microscopic magnetic resonance imaging (MMRI), a high-resolution tool
      able to detect subtle changes of vessels in small animals. MATERIAL/METHODS:
      Fetuses from pregnant rats fed either 100 mg i.g. nitrofen or vehicle on E9.5
      were recovered near term. A 7 T MMRI system with a coronal multislice fast spin
      echo sequence allowed diagnosis of CDH (n = 19), and T2 SE high-resolution
      sequences made assessment of the pattern and width of cervico-thoracic veins
      possible. Values were corrected for body size by dividing them by the length of
      thoracic vertebrae T3-T5. The results in nitrofen and control (n = 11) groups
      were compared by non-parametric tests (*p < 0.05). RESULTS: Congenital
      diaphragmatic hernia fetuses were smaller than controls (4.5 +/- 0.26 vs. 5.3 +/-
      0.2 g*). The widths (corrected for body size) of left external, both innominate,
      right superior vena cava and azygos veins were significantly smaller in CDH rats
      than in controls. CONCLUSIONS: The cervico-thoracic veins are normally patterned
      but abnormally narrow (except the internal jugulars) in rats with CDH. The same
      embryonic NC dysregulation that accounts for cardiovascular malformations could
      also explain these venous anomalies in CDH.

PMID- 21069350
TI  - Abnormal development of the enteric nervous system in rat embryos and fetuses
      with congenital diaphragmatic hernia.
AB  - BACKGROUND/AIM: Esophageal dilatation, gastroesophageal reflux, and intestinal
      obstruction have been demonstrated in CDH survivors. Abnormal esophageal and
      intestinal innervations were recently found in rats and babies with this disease.
      Our aim was to further characterize these malformations in embryos and fetal rats
      exposed to nitrofen. METHODS: Pregnant rats received either 100 mg nitrofen or
      vehicle on E9.5. Fetuses were recovered at E15, E18, and E21. Sections of
      esophagus and small bowel were histochemically stained with acetylcholinesterase
      (AChE) and immunostained for PGP9.5. PGP9.5 gen protein were measured on E21 and
      PGP9.5 mRNA on E15, E18 and E21. Comparisons between groups were made with non
      parametrics tests. RESULTS: Histochemistry and immunohistochemistry showed
      deficient innervation in all anatomical areas studied at E15, E18, and E21, and
      WB confirmed this decrease in E21 fetuses. PGP9.5 messenger was decreased in
      nitrofen-exposed animals on E18 (esophagus) or E15 (small bowel), and increased
      on E21 in the esophagus and E18 in small bowel. CONCLUSIONS: Development of the
      enteric nervous system of the esophagus, stomach, and small bowel is deficient in
      rat embryos and fetuses exposed to nitrofen. These anomalies could account in
      part for the long-term gastrointestinal morbidity observed in CDH survivors.

PMID- 21069351
TI  - The Skt gene, required for anorectal development, is a candidate for a molecular
      marker of the cloacal plate.
AB  - BACKGROUND AND AIMS: It has been reported that a dorsal cloacal plate defect is
      associated with anorectal malformations (ARMs); however, there has been very
      little information reported about the developmental mechanisms involved with
      cloacal plate formation. Danforth's short tail (Sd) mutant mice show ARMs. In our
      previous study, the co-presence of Skt ( Gt ) mutation, in which Skt gene is
      disrupted by the gene-trap vector (p-U8), increased the incidence of ARMs in Sd
      mutant to 100%. Our aims in this study are determining the Skt expression around
      the cloaca during the anorectal development and demonstrating the role of Skt
      gene in ARMs. METHODS: Embryos, normal controls [+Skt ( Gt )/+Skt ( Gt )] and
      ARMs models [Sd Skt ( Gt )/+Skt ( Gt )], from embryonic day (E) 9.5 to E12.5,
      were evaluated with X-gal staining. RESULTS: In control embryos, Skt expression
      was detected both in the endoderm and ectoderm of the cloacal plate from E9.5
      onward. At E12.5, Skt expression was also detected in the mesenchyme neighboring
      the dorsal cloacal plates. In [Sd Skt ( Gt )/+Skt ( Gt )] mutant embryos, the
      cloacal plates failed to extend proximodistally and, consequently, the dorsal
      part of cloacal plate was defective at E11.5. Skt expressing cells were detected
      in the shortened cloacal plate and in the thickened mesenchyme dorsal to it.
      CONCLUSIONS: We showed the spatial and temporal expression of Skt gene in the
      cloacal plate formation. This gene could be a marker for the cloacal plate during
      the anorectal development. Furthermore, Skt was considered to be associated with
      the embryogenesis of ARMs.

PMID- 21069352
TI  - Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the
      nitrofen-induced hypoplastic lung in late gestation.
AB  - PURPOSE: Pulmonary hypoplasia (PH), the leading cause of mortality in congenital
      diaphragmatic hernia (CDH), is associated with arrested alveolarization. Late
      gestation lung protein 1 (LGL1) plays a crucial role in the regulation of
      alveolarization. Inhibition of LGL1 impairs alveolar maturation in fetal rat
      lungs. LGL1 heterozygotus knockout mice display delayed lung maturation. It is
      well known that prenatal administration of retinoic acid (RA) stimulates
      alveologenesis in nitrofen-induced PH. In vitro studies have reported that RA is
      a key modulator of LGL1 during alveologenesis. We hypothesized, that pulmonary
      gene expression of LGL1 is downregulated in the late stage of lung development,
      and that prenatal administration of RA upregulates pulmonary LGL1 expression in
      the nitrofen CDH model. METHODS: Pregnant rats were exposed to nitrofen on day 9
      (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Fetal
      lungs were dissected on D21 and divided into control, control + RA, CDH and CDH +
      RA group. Expression levels of LGL1 were determined using RT-PCR and
      immunohistochemistry. RESULTS: On D21, LGL1 relative mRNA expression levels were
      significantly downregulated in CDH group compared to controls. After RA
      treatment, gene expression levels of LGL1 were significantly upregulated in CDH +
      RA and control + RA compared to CDH group. Immunohistochemical studies confirmed
      these results. CONCLUSION: Downregulation of pulmonary LGL1 gene expression in
      the late stage of lung development may interfere with normal alveologenesis.
      Upregulation of LGL1 pulmonary gene expression after RA treatment may promote
      lung growth by stimulating alveologenesis in the nitrofen CDH model.

PMID- 21069353
TI  - Disruption of GLI3-ZIC3 interaction in the cadmium-induced omphalocele chick
      model.
AB  - PURPOSE: Administration of heavy metal cadmium (Cd) after 60-h incubation induces
      omphalocele spectrum in the chick embryo. Although previous studies have shown
      that the earliest detectable histological changes in the chick Cd model occurs
      commencing at 4-h post-treatment (4H). However, the molecular mechanism by which
      Cd acts in the critical period of early embryogenesis still remains unclear.
      Zic3, a Gli superfamily transcription factor, is expressed in somites and plays
      an important role in vertebrate development, including somitogenesis and thus
      ventral body wall formation. Gli3 is also expressed in somites and interacts with
      Zic3 physically and functionally. It has been reported that Gli3 homozygous
      double mutants display omphalocele. Zic3 mutant mice have also been known to
      result in omphalocele phenotype. We designed this study to test the hypothesis
      that Gli3 and Zic3 gene expression is downregulated during the critical period of
      very early embryogenesis in the Cd-induced omphalocele in the chick model.
      METHODS: After 60-h incubation, chick embryos were exposed to either saline or 50
      MUM cadmium and divided into two groups: control and Cd (n = 24 for each group).
      Real-time reverse transcription polymerase chain reaction was performed to
      evaluate the relative mRNA expression levels of Gli3 and Zic3 in the Cd-induced
      omphalocele chick model. Differences between the two groups at each time point
      were analyzed statistically and the significance was accepted at p < 0.05.
      Immunohistochemistry was also performed to evaluate the expression/distribution
      of those proteins in chick embryo. RESULTS: The relative mRNA expression level of
      Gli3 and Zic3 was significantly decreased in the Cd group at 4H when compared
      with controls (p < 0.05). However, there were no significant differences at the
      other time points. At 4H, immunoreactivity of GLI3 and ZIC3 was also markedly
      decreased in Cd-treated embryos, whereas strong expression of them was seen in
      the somite in controls. CONCLUSION: We provide evidence, for the first time, that
      Gli3 and Zic3 gene expression is downregulated during the narrow window of very
      early embryogenesis in Cd chick model. Disruption of Gli3-Zic3 interaction in the
      critical period for ventral body wall formation may contribute to omphalocele
      phenotype in Cd chick model.

PMID- 21069354
TI  - Downregulation of Midkine gene expression and its response to retinoic acid
      treatment in the nitrofen-induced hypoplastic lung.
AB  - PURPOSE: Nitrofen-induced congenital diaphragmatic hernia (CDH) model has been
      widely used to investigate the pathogenesis of pulmonary hypoplasia (PH) in CDH.
      Recent studies have suggested that retinoids may be involved in the molecular
      mechanisms of PH in CDH. Prenatal treatment with retinoic acid (RA) has been
      reported to improve the growth of hypoplastic lung in the nitrofen CDH model.
      Midkine (MK), a RA-responsive growth factor, plays key roles in various
      organogenesis including lung development. In fetal lung, MK mRNA expression has
      its peak at E13.5-E16.5 and is markedly decreased during mid-to-late gestation,
      indicating its important role in early lung morphogenesis. We designed this study
      to investigate the hypothesis that the pulmonary MK gene expression is
      downregulated in the early lung morphogenesis in the nitrofen-induced PH, and to
      evaluate the effect of prenatal RA treatment on pulmonary MK gene expression in
      the nitrofen-induced CDH model. METHODS: Pregnant rats were exposed to either
      olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on
      D15, D18, and D21 and divided into control, nitrofen with or without CDH [CDH(+)
      or CDH(-)]. In addition, RA was given on days D18, D19, and D20 and fetal lungs
      were harvested on D21, and then divided into control + RA and nitrofen + RA. The
      pulmonary gene expression levels of MK were evaluated by real-time RT-PCR and
      statistically analyzed. Immunohistochemistry was also performed to examine
      protein expression/distribution of MK in fetal lung. RESULTS: The relative mRNA
      expression levels of MK were significantly downregulated in nitrofen group
      compared to controls at D15 ((S)p < 0.01), whereas there were no significant
      differences at D18 and D21. MK gene expression levels were significantly
      upregulated in nitrofen + RA (0.71 +/- 0.17) compared to the control (0.35 +/-
      0.16), CDH(-) (0.24 +/- 0.15), CDH(+) (0.39 +/- 0.19) and control + RA (0.47 +/-
      0.13) (*p < 0.05). Immunoreactivity of MK was also markedly decreased in nitrofen
      lungs compared to controls on D15, and increased in nitrofen + RA lungs compared
      to the other lungs on D21. CONCLUSION: Downregulation of MK gene on D15 may
      contribute to primary PH in the nitrofen CDH model by disrupting early lung
      morphogenesis. Upregulation of MK gene after RA treatment in the nitrofen-induced
      hypoplastic lung suggests that RA may have a therapeutic potential to rescue PH
      in CDH through RA-responsive growth factor signaling.

PMID- 21069355
TI  - A simplified rehabilitation program for patients undergoing elective colonic
      surgery--randomized controlled clinical trial.
AB  - BACKGROUND: We have proposed a simplified perioperative rehabilitation program
      for elective colonic surgery that is focused on early oral nutrition and that
      could reduce hospital stay and postoperative ileus time without raising
      complications and readmission rates. PATIENTS AND METHODS: Fifty-four patients
      admitted for elective colonic surgery were prospectively randomized into two
      groups: (1) an early feeding group (EFG)-on the first postoperative day, patients
      initially received a oral liquid diet and were advanced to a regular diet within
      the next 24 h as tolerated and at their discretion; (2) a traditional care group
      patients were managed by nothing per orus until the elimination of the first
      flatus and then submitted to an oral liquid diet, followed by a regular diet
      within the next 24 h as described for the EFG. All patients followed a well
      defined, simplified rehabilitation program. RESULTS: Patients' baseline
      characteristics were similar in the two groups. Hospital stay was significantly
      lower in the EFG (4.0 [+/-3.7] versus 7.6 [+/-8.1] days; p = 0.000). Diet
      tolerance and progression were similar between groups. Time to first flatus after
      surgery was significantly lower in the EFG (1.5 [+/-0.5] versus 2.0 [+/-0.7]
      days; p = 0.019). Complication and readmission rates were similar in both groups.
      CONCLUSIONS: Early oral nutrition associated with a simplified perioperative
      rehabilitation program reduces postoperative length of hospital stay and ileus
      time after elective colonic resection without increasing rates of complications
      or readmissions.

PMID- 21069356
TI  - Advancement anoplasty and sacral nerve stimulation: an effective combination for
      radiation-induced anal stenosis.
AB  - INTRODUCTION: Pelvic radiotherapy can cause anal stenosis. Patients can be left
      with severe rectal evacuatory difficulties, anal fissuring and resistant faecal
      incontinence. The management of such patients is difficult since surgical
      treatment can worsen faecal incontinence. CASE STUDY: We report a patient who was
      treated for recurrent fissuring and faecal incontinence secondary to severe anal
      stenosis caused by external beam radiotherapy to his prostate. A 74-year-old male
      patient underwent excision of the fissuring, fibrotic anal mucosa and internal
      sphincter and was then treated with a broad-based House advancement anoplasty.
      The patient's fissuring was successfully treated but he still suffered from
      faecal incontinence. The patient underwent sacral nerve stimulation with
      significant improvement in all faecal incontinence symptoms. CONCLUSION: The use
      of a novel combination of a House advancement anoplasty and sacral nerve
      stimulation is a safe and effective treatment rationale for treatment of
      radiation-induced anal stenosis.

PMID- 21069357
TI  - Posterior tibial nerve stimulation and faecal incontinence: a review.
AB  - PURPOSE: Faecal incontinence is a common and important multifactorial disorder
      with a range of treatment options. Over the last two decades, neuromodulation via
      sacral nerve stimulators has been shown to be effective for both faecal and
      urinary incontinence, although associated with complications. Peripheral
      neuromodulation, via the posterior tibial nerve, is widely used in urinary
      incontinence; however, its use in faecal incontinence, whilst evolving is limited
      to eight small heterogeneous studies. REVIEW: These eight studies are discussed
      in the context of the methodology and underlying neurophysiology of peripheral
      neuromodulation, as are thus far unanswered questions. The eight studies include
      a total of 129 patients with faecal incontinence (of variable aetiology), all of
      whom had failed conservative management. One study was prospective and
      controlled, six were uncontrolled and one was retrospective and uncontrolled.
      Five different neuromodulatory protocols were used over six different study
      periods. Outcome measures varied, but short term primary endpoint success ranged
      from 30.0% to 83.3%. The limitations to this early evidence, whilst encouraging,
      are significant, and it remains to be seen whether this novel treatment modality
      represents the minimally invasive, well-tolerated, cost-effective and flexible
      panacea hoped for this common and debilitating disease. Three upcoming
      multicentre placebo-controlled trials will better be able to delineate its role.

PMID- 21069358
TI  - Transforming growth factor beta 1 (TGF-beta 1) in atrial fibrillation and acute
      congestive heart failure.
AB  - PURPOSE: Atrial fibrillation (AF) and acute congestive heart failure (aCHF) are
      characterized by an adverse cardiac remodeling. Arrhythmogenic or structural
      remodeling can be caused by interstitial fibrosis. Transforming growth factor
      beta 1 (TGF-beta 1) represents a central regulator of cardiac fibrosis. This
      study investigates serum levels of TGF-beta 1 in patients with AF and aCHF.
      METHODS: 401 patients presenting with symptoms of dyspnea or peripheral edema
      were prospectively enrolled. Blood samples for measurement of TGF-beta 1 (R&D
      Systems, Inc.) and amino-terminal pro-brain natriuretic peptide (NT-proBNP)
      (DadeBehring ltd.) were collected after the initial clinical evaluation. RESULTS:
      Median TGF-beta 1 levels were lower in patients with AF (21.0 ng/ml,
      interquartile range (IR) 15.4-27.6 ng/ml, n = 107) compared to those without
      (25.0 ng/ml, IR 18.5-31.6 ng/ml, n = 294) (p = 0.009). Patients with aCHF had
      lower TGF-beta 1 levels (median 22.0 ng/ml, IR 15.6-27.1 ng/ml, n = 122) than
      those without (median 24.9 ng/ml, IR 18.1-31.9 ng/ml, n = 279) (p = 0.0005). In
      logistic regression models TGF-beta 1 was still associated with AF (odds ratio
      (OR) 3.00, 95% CI 1.37-6.61, p = 0.0001) and aCHF (OR 3.98, 95% CI 1.55-10.19, p
      = 0.004). TGF-beta 1 inversely correlated with left atrial diameter (r = -0.30, p
      = 0.007) and NT-proBNP (r = -0.14, p = 0.007). CONCLUSIONS: Low serum levels of
      TGF-beta 1 are associated with AF and aCHF. This decrease may result from a
      higher consumption of TGF-beta 1 within the impaired myocardium or antifibrotic
      functions of natriuretic peptides.

PMID- 21069360
TI  - Mutation-specific IDH1 antibody differentiates oligodendrogliomas and
      oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology.
AB  - Isocitrate dehydrogenase 1 (IDH1) mutations are frequent in astrocytomas,
      oligoastrocytomas and oligodendrogliomas. We previously reported the generation
      of a mutation-specific antibody that specifically detects R132H mutated IDH1
      protein (clone H09). Here, we investigate the feasibility of H09
      immunohistochemistry to differentiate between
      oligodendrogliomas/oligoastrocytomas and other tumors with similar morphology. A
      total of 274 brain tumors presenting with focal or extensive clear cell
      morphology were investigated. High numbers of H09-positive cases were observed in
      adult grade II oligodendrogliomas (67 of 74, 91%), grade III oligodendrogliomas
      (65 of 69, 94%), grade II oligoastrocytomas (11 of 14, 79%) and grade III
      oligoastrocytomas (10 of 11, 91%). All cases of pediatric oligodendrogliomas (n =
      7), neurocytomas (n = 41, 35 central, 4 extraventricular, 2 cerebellar
      liponeurocytomas), dysembryoplastic neuroepithelial tumors (n = 21), clear cell
      ependymomas (n = 8), clear cell meningiomas (n = 9) as well as 12 primary
      glioblastomas with oligodendroglial differentiation and 5 pilocytic astrocytomas
      with oligodendroglial-like differentiation were negative for H09
      immunohistochemistry. Three oligodendrogliomas with neurocytic differentiation
      had evidence of IDH1/IDH2 mutations either by H09 immunohistochemistry or direct
      sequencing. We conclude that in tumors with an oligodendroglioma-like morphology,
      binding of H09 is highly specific for oligodendrogliomas or oligoastrocytomas and
      substantially helps in the discrimination from other clear cell tumors. Negative
      H09 immunohistochemistry of an adult oligodendroglioma or oligoastrocytoma should
      prompt the consideration of other clear cell neoplasms. Further, our observations
      firmly assign oligodendrogliomas with neurocytic differentiation to the group of
      oligodendrogliomas and demonstrate that H09 is especially helpful for the
      difficult discrimination of such lesions from extraventricular neurocytomas.

PMID- 21069361
TI  - Three kinds of forearm flaps for hand skin defects: experience of 65 cases.
AB  - INTRODUCTION: Reverse radial forearm flap has been proven reliable and effective
      for hand reconstruction. Here we report our experience with the use of reverse
      forearm flap that does not contain the radial or ulnar artery for reconstruction
      of hand defects in 65 cases with soft tissue defects of the hand. METHOD: Sixty
      five patients who sought surgical treatment for soft tissue defects of the hand
      at our hospital between January 2003 and December 2008 were included in the
      study. 39 cases had soft tissue defect on the dorsal aspect of the hand and 26
      cases on the palmar aspect of the hand. 65 flaps were performed with the
      posterior interosseous artery flap in 26 cases, island flap supplied by the
      distal cutaneous branch of the ulnar artery in 23 cases, and the flap based on
      distally perforator of the radial artery in sixteen cases with the size of the
      flaps ranging from 5 to 12 cm in length and from 4 to 8 cm in width. RESULTS: The
      distal cutaneous branch of the ulnar artery flap showed partial necrosis (25-35%
      of their area) in two cases. Both the donor and the recipient sites healed
      successfully in other cases. At 8.4 months of follow up, all patients had
      insensitivity in recipient sites. No patient complained of cold intolerance,
      pain, numbness and so on in the forearm and hand. According to the TAM criteria
      (the total active motion of the finger joint) and DASH (Disability of the Arm,
      Shoulder, and Hand) score showed that postoperative functions were excellent and
      symptoms were minor, with no significant differences among the groups (P > 0.05).
      CONCLUSION: Our results indicated that the reverse forearm flap preserving the
      radial and ulnar artery is a reliable and effective method to cover skin defects
      of the hand.

PMID- 21069362
TI  - Biomechanical analysis of bicortical versus unicortical locked plating of mid
      clavicular fractures.
AB  - OBJECTIVES: Operative fixation of displaced mid-shaft clavicle fractures has been
      shown to improve the functional outcomes and decrease the likelihood of non
      union; however, little is known about the need for locking screws versus
      traditional screws. We, therefore, evaluated the strength of unicortical locked
      plating versus traditional bicortical non-locking fixation methods. METHODS: Ten
      matched pairs of fresh, frozen cadaver clavicle specimens were obliquely
      osteotomized through the mid-shaft to represent the most common fracture pattern.
      After randomization, the clavicles were repaired using pre-contoured plates with
      either standard bicortical non-locking screws or unicortical locking screws. The
      constructs were then potted in cement and tested on a MTS machine using a custom
      gimble and evaluated for load to failure and axial and rotational stiffness.
      RESULTS: There was no significant difference between the constructs in terms of
      axial stiffness (locking 688.3 +/- 306.2 N/mm, non-locking 674.5 +/- 613.0 N/mm;
      p = 0.77) or load to failure (locking 720.1 +/- 232.0 N, non-locking 664.8 +/-
      167.5 N; p = 0.46). However, rotational stiffness varied significantly (locking
      1.70 +/- 0.91 N-m/mm, non-locking 2.49 +/- 0.78 N-m/mm, p = 0.049) with
      bicortical non-locking constructs exhibiting higher torque values. CONCLUSIONS:
      Unicortical fixation using pre-contoured plates and locking screws has a similar
      biomechanical profile compared to gold standard non-locked bicortical screws in
      cyclic axial compression and axial load to failure. Non-locking constructs were
      stiffer under rotational testing. This technique may provide a suitable
      biomechanical environment for bony healing. This may also improve the safety of
      clavicle plating by protecting infraclavicular structures from injury during
      drilling or screw penetration as it obviates the need for bicortical fixation.

PMID- 21069363
TI  - Influence of femoral malrotation on knee joint alignment and intra-articular
      contract pressures.
AB  - INTRODUCTION: The standard treatment of femoral diaphyseal fractures is
      intramedullary nailing. Torsion error remains a largely unsolved problem. We
      hypothesized that femoral malrotation would change the coronal alignment of the
      lower extremity and the center of force (COF) in the tibiofemoral joint as
      compared to the native state. METHOD: Ten cadaveric legs were used.
      Intraarticularly placed sensor foil was used to measure contact pressures for
      each condyle. The resultant pressure of this two-force measurement was calculated
      as the COF for the joint. Mechanical axis was defined by the navigation system.
      Two novel devices were used: (1) to simulate bodyweight with leg attachment and
      fixation to the anterior pelvis and (2) to fix the femur at various degrees of
      malrotation. A mid-diaphyseal osteotomy was performed and the distal fragment was
      rotated both internally and externally in 5 degrees  increments to a maximum of
      25 degrees . COF and axial alignment were assessed at each step with application
      of a half-bodyweight specific to each specimen. RESULTS: Internal rotation
      resulted in valgus deviation of the mechanical axis and a shift in COF towards
      the lateral condyle (P < 0.05). External rotation caused varus deviation and
      switched COF towards the medial condyle (P < 0.05). This study shows that femoral
      malrotation has a significant effect on mechanical axis alignment and force
      vectors within the knee. Correlation with clinical outcomes is necessary and
      further research into minimizing such errors of torsion is warranted. CONCLUSION:
      Torsion errors are not merely cosmetic issues, but may result in further
      morbidity, such as varus or valgus deformity and shifting of the COF, which may
      lead to joint arthrosis.

PMID- 21069364
TI  - Comparative study on the efficacy of two-staged (posterior followed by anterior)
      surgical treatment using spinal instrumentation on pyogenic and tuberculotic
      spondylitis.
AB  - INTRODUCTION: Between 1997 and 2006, we treated 11 patients with tuberculotic
      spondylitis and 19 with pyogenic spondylitis using a two-staged operation
      (posterior spinal instrumentation, followed by anterior debridement and fusion).
      METHOD: We compared changes in inflammatory reactions, postoperative
      complications, organisms obtained during anterior debridement, neurological
      status, bone union, and suppression of the infection between the patients with
      tuberculotic and pyogenic spondylitis. PATIENTS: All patients in both groups
      achieved bone union and suppression of the infected sites. Decreases in C
      reactive protein and erythrocyte sedimentation rate were significantly slower in
      the patients with tuberculotic spondylitis. Positive bacterial cultures at the
      second anterior debridement were obtained from 26% of patients with pyogenic
      spondylitis and 55% of patients with tuberculotic spondylitis. Frankel types
      improved in 57% of patients, but there were no differences in neurological
      improvement. The efficacy of the two-staged operation did not differ between the
      patients with pyogenic and tuberculotic spondylitis. RESULTS: Although the
      baselines were different, there were no significant differences in relative
      operating parameters, neurological improvement, or postoperative complications
      between the two groups. At the final follow-up, all patients finally achieved
      suppression of spinal infection and solid bone fusion in both groups, although
      the decline in inflammatory parameters was slower in the T group than in the P
      group.

PMID- 21069365
TI  - Newcastle approach to the elbow, a cadaveric study.
AB  - AIM: The aim of the current study was to assess the amount of the distal humerus
      articular surface exposed through the Newcastle approach, a posterior triceps
      preserving exposure of the elbow joint. METHOD: Twenty-four cadaveric elbows (12
      pairs) were randomized to receive one of the four posterior surgical approaches:
      triceps reflecting, triceps splitting, olecranon osteotomy and Newcastle
      approach. The ratio of the articular surface exposed for each elbow was
      calculated and compared. RESULTS: The highest ratio observed was for Newcastle
      approach (0.75 +/- 0.12) followed by olecranon osteotomy (0.51 +/- 0.1), triceps
      reflecting (0.37 +/- 0.08) and triceps splitting (0.35 +/- 0.07). The differences
      between Newcastle approach and other approaches were statistically significant (p
      = 0.003 vs. osteotomy and <0.0001 vs. triceps reflecting and splitting).
      CONCLUSION: The Newcastle approach sufficiently exposes the distal humerus for
      arthroplasty or fracture fixation purposes. Its use is supported by the current
      study.

PMID- 21069366
TI  - Focus on haematogenous dissemination of the malignant cystosarcoma phylloides:
      institutional experience.
AB  - INTRODUCTION: Cystosarcoma phylloides (CSP) is a fibro-epithelial neoplasm of the
      breast. Not all CSP cases present as malignant tumors; they are therefore
      classified as benign, malignant, and borderline subtypes according to the WHO
      classification. The classification is based on several histopathological features
      of the neoplasm, such as mitosis rate or invasive growth of the tumor. The
      progression of this disease is mainly influenced by the classification of their
      degree. In western countries, this tumor entity usually occurs between 50 and 60
      years of age. The major problem in the handling of these patients is the high
      local recurrence rate, whereas haematogenous metastasis is seldom seen. We
      therefore report three cases of haematogenous spread in a group of eight patients
      (two borderline and six malignant cases of CSP). MATERIALS AND METHODS: In this
      study, we investigated all patients suffering from malignant or borderline CSP,
      between May 1995 and January 2009, who were under the care of the Department of
      Gynecology and Obstetrics, University Hospital, Ulm. A written and informed
      consent was obtained from all patients included in this retrospective study.
      During this period, eight patients, fulfilling the criteria discussed before,
      were under the care of the Department of Gynecology and Obstetrics. All
      therapeutic decisions were taken by the interdisciplinary tumor board of the
      department (after 1999). RESULTS: In the retrospective analysis of our study
      group, we found a high percentage of haematogenous metastasis that was always
      accompanied with a very poor prognosis in malignant CSP patients. Those patients
      always died within a short period of time. Two of these patients showed, while
      they underwent initial surgery, no metastatic suspect lesions and underwent R0
      resection; both received a radical mastectomy. One patient already showed lung
      metastasis while undergoing first line surgery, because she initially declined
      surgery. We therefore speculate that postoperative adjuvant chemotherapy could
      lead to a favorable outcome in high risk patients, concerning the development of
      haematogenous metastasis.

PMID- 21069367
TI  - Maternal early pregnancy body mass index and risk of preterm birth.
AB  - OBJECTIVE: To determine the association between maternal body mass index (BMI) in
      early pregnancy and the risk of preterm birth (PTB) in Chinese women. METHODS:
      Data were obtained from a population-based perinatal care program in China during
      1993-2005. Women whose height and weight information was recorded at the first
      prenatal visit in the first trimester of pregnancy and delivered a singleton live
      infant were selected. Women with multiple gestations, stillbirths, delivery
      before 28 weeks or after 44 weeks of gestation, and infants affected by major
      external birth defects were excluded. BMI was categorized as underweight (less
      than 18.5 kg/m(2)), normal weight (18.5-23.9 kg/m(2)), overweight (24-27.9
      kg/m(2)), and obese (>=28 kg/m(2)) based on BMI classification criteria for
      Chinese. Logistic regression analysis was conducted to adjust for potential
      confounders, such as maternal age, education, occupation, city or county, gender
      of infant, and year of delivery. RESULTS: A total of 353,477 women were selected.
      The incidence of preterm birth in women who were underweight, normal weight,
      overweight, obese was 3.69% (3.61-3.76%), 3.59% (3.55-3.62%), 3.83% (3.71-3.96%),
      4.90% (4.37-5.43%), respectively. The incidence of elective preterm birth,
      overweight, and obesity increased remarkably during 2000-2005 compared with that
      during 1993-1996. After having adjusted for potential confounders including
      maternal age, maternal occupation, education, city or county, gender of the
      infant and year of birth, the risk of PTB increased significantly with BMI (P <
      0.05). Among nulliparae, the risk of elective preterm birth increased with
      increasing BMI. Nulliparae who were underweight were less likely to deliver
      elective preterm births (OR = 0.89, 95% CI 0.80-0.98). Nulliparae who were
      overweight and obese in early pregnancy were at a greater risk of elective PTB
      than normal weight nulliparae (for the overweight OR = 1.36, 95% CI 1.18-1.56,
      for the obese OR = 2.94, 95% CI 2.04-4.25). CONCLUSION: In this study, indigenous
      Chinese cohort women who are overweight, obese, and nulliparous are at an
      increased risk of elective preterm birth.

PMID- 21069368
TI  - Highly elevated serum CA-125 levels in patients with non-malignant gynecological
      diseases.
AB  - PURPOSES: To identify patients with highly elevated serum CA-125 levels and
      analyze their clinical characteristics. METHODS: Patients with non-malignant
      gynecologic disease (NMGDs, n = 41), in whom serum CA-125 levels were over 1,000
      IU/ml were retrospectively enrolled in the study. Seventy-one patients with
      epithelial ovarian cancer (EOC), in whom, serum CA-125 levels were over 1,000
      IU/ml were included as the comparison group. Clinical parameters were compared
      between the two groups. RESULTS: In NMGDs group, 43.90% of the patients had
      endometriosis. The median of serum CA-125 level in NMGDs was much lower than that
      of EOC subjects (P < 0.001). Compared to EOC group, the patients in NMGDs group
      were much younger (P < 0.001) and had fewer histories of pelvic masses (P <
      0.001) but had more clinical complaints such as acute abdominal symptoms (P <
      0.001) and/or abnormal vaginal bleeding (P = 0.022). Clinical progresses of these
      two groups were correlated with changes of serum CA-125 levels by follow-up for
      up to 386 days. CONCLUSIONS: High levels of serum CA-125 were found not only in
      the EOC, but also in some NMGDs, especially in the reproductive patients with
      complaints of acute abdomen symptoms or abnormal vaginal bleeding.

PMID- 21069369
TI  - Residual dizziness after successful repositioning maneuvers for idiopathic benign
      paroxysmal positional vertigo in the elderly.
AB  - Even after successful repositioning maneuvers for benign paroxysmal positional
      vertigo (BPPV), some patients report dizziness lasting for a certain period
      afterwards. We studied the prevalence and clinical factors associated with
      residual dizziness in a sample of elderly patients. Sixty outpatients over 65
      years of age, affected by idiopathic BPPV were recruited; the exclusion criterion
      was a history of previous episodes of vertigo, including positional. The patients
      were asked to describe their self-perceived anxiety for vertigo on a Visual
      Analogue Scale (VAS) and successively treated with appropriate maneuvers till
      resolution of nystagmus. Data concerning the demographic and clinical features of
      BPPV were collected. Patients were followed until complete resolution of
      subjective dizziness and imbalance without positional nystagmus. Data about
      residual dizziness were collected from the second day from resolution of BPPV.
      Clinical and demographic factors related to residual dizziness were analyzed.
      Twenty-two subjects (37%) reported residual dizziness. In these subjects, the
      mean duration of residual dizziness was 13.4 +/- 7.5 days. No association was
      observed between residual dizziness and gender, involved canal and the number of
      repositioning maneuvers before resolution. On the other hand, age older than 72
      years, symptom duration greater than 9 days and VAS scale for anxiety greater
      than 10/100 were associated with an increased risk of residual dizziness. The
      odds ratio were respectively 6.5 (age-residual dizziness, Confidence Interval
      95%), 6.5 (duration of vertigo-residual dizziness, Confidence Interval 95%) and
      15.5 (anxiety levels-residual dizziness, Confidence Interval 95%). Longer symptom
      duration before diagnosis was associated with higher anxiety levels. The results
      underline the necessity for an early and correct diagnosis of BPPV, especially in
      the elderly.

PMID- 21069370
TI  - Incidence and clinical value of prolonged I-V interval in NICU infants after
      failing neonatal hearing screening.
AB  - Infants admitted to neonatal intensive care units (NICUs) have a higher incidence
      of perinatal complications and delayed maturational processes. Parameters of the
      auditory brainstem response (ABR) were analyzed to study the prevalence of
      delayed auditory maturation or neural pathology. The prevalence of prolonged I-V
      interval as a measure of delayed maturation and the correlation with ABR
      thresholds were investigated. All infants admitted to the NICU Sophia Children's
      Hospital between 2004 and 2009 who had been referred for ABR measurement after
      failing neonatal hearing screening with automated auditory brainstem response
      (AABR) were included. The ABR parameters were retrospectively analyzed. Between
      2004 and 2009, 103 infants were included: 46 girls and 57 boys. In 58.3% (60
      infants) of our population, the I-V interval was recordable in at least one ear
      at first diagnostic ABR measurement. In 4.9%, the I-V interval was severely
      prolonged. The median ABR threshold of infants with a normal or mildly prolonged
      I-V interval was 50 dB. The median ABR threshold of infants with a severely
      prolonged I-V interval was 30 dB. In conclusion, in case both peak I and V were
      measurable, we found only a limited (4.9%) incidence of severely prolonged I-V
      interval (>=0.8 ms) in this high-risk NICU population. A mild delay in maturation
      is a more probable explanation than major audiologic or neural pathology, as ABR
      thresholds were near normal in these infants.

PMID- 21069371
TI  - Estimating time of death based on the biological clock.
AB  - The biological clock may stop at the time of death in a dead body. Therefore, the
      biological clock seems useful for estimating the time of death. In this study, we
      tried to read the biological clock in tissues from dead bodies to estimate the
      time of death using molecular biological techniques. At first, we examined real
      time RT-PCR analysis of gene expression for mPer2 and mBmal1, which constitutes a
      feedback loop in the oscillation system, in the kidney, liver, and heart of mice.
      We could detect circadian oscillation of these gene expressions in mouse tissues
      even at <48 h after death. Thus, the ratio of mPer2/mBmal1 was found to be useful
      for estimating the time of death. We next applied this method to the liver,
      kidney, and heart obtained from forensic autopsy cases with less than 72 h of
      postmortem interval. Significant circadian oscillation of hPer2/hBmal1 ratio
      could be detected in these autopsy samples. We further examined gene expression
      for hRev-Erbalpha, a component of another feedback loop. The ratios of hRev
      Erbalpha/hBmal1 showed higher amplitude of oscillation than those of hPer2/hBmal1
      and are considered more suitable for estimating the time of death. In particular,
      a hRev/hBmal1 ratio of >50 indicated the time of death as 0200-0900 hours, and a
      hRev/hBmal1 ratio that considerably exceeded 75 indicated the time of death as
      0200-0800 hours. On the other hand, a hRev/hBmal1 ratio of less than 25 strongly
      indicated the time of death as 1000-2300 hours. Taken together, these findings
      indicate that gene expression analyses of the biological clock could be powerful
      methods for estimation of the time of death.

PMID- 21069373
TI  - Differential diameter responses in macular and peripheral retinal arterioles may
      contribute to the regional distribution of diabetic retinopathy lesions.
AB  - BACKGROUND: Diabetic retinopathy is assumed to be due to impaired retinal
      autoregulation, involving both pressure autoregulation and metabolic
      autoregulation. The disease displays regional differences, with signs of
      hyperperfusion in the macular area and capillary occlusion with retinal ischemia
      in the peripheral retinal areas. It can be hypothesized that these regional
      differences in the occurrence of retinopathy lesions may reflect differences in
      the capacity of retinal arterioles to autoregulate the diameter of retinal
      arterioles. METHODS: Seventeen normal persons and two matched groups of patients
      with respectively diabetic maculopathy and proliferative diabetic retinopathy
      were examined. The diameter change of a macular and a peripheral retinal
      arteriole during an increase in the arterial blood pressure induced by isometric
      exercise, during an increase in retinal metabolism induced by flicker
      stimulation, and during both stimulus paradigms simultaneously were studied using
      the dynamic vessel analyzer (DVA). RESULTS: During isometric exercise, the
      diameter response was reduced in both macular and peripheral retinal arterioles
      in the two groups of patients with diabetes mellitus. During flicker stimulation,
      the diameter response was significantly reduced in patients with proliferative
      diabetic retinopathy, but there was no significant difference between the
      responses of macular and peripheral arterioles. During simultaneous isometric
      exercise and flicker stimulation, there was no difference between the diameter
      response of macular arterioles in the three groups, whereas the diameter response
      of macular arterioles was significantly lower in normal persons and significantly
      higher in persons with proliferative diabetic retinopathy as compared to
      peripheral arterioles. CONCLUSIONS: Regional differences in the disturbances of
      the diameter response to increased blood pressure may contribute to the regional
      differences in the distribution of diabetic retinopathy lesions. In the central
      retinal areas, the diameter response to increased blood pressure and retinal
      metabolism interacted in a way that may potentially protect this area from
      ischaemia, whereas this protective mechanism was absent in the peripheral retinal
      arterioles. An elucidation of the mechanisms underlying diameter regulation to
      increased blood pressure and retinal metabolism, and the interaction between
      these two mechanisms, may help in understanding the pathophysiology of diabetic
      retinopathy.

PMID- 21069372
TI  - Immunohistochemical examination of intracerebral aquaporin-4 expression and its
      application for differential diagnosis between freshwater and saltwater drowning.
AB  - Human brain samples were collected from 70 autopsy cases including 22 freshwater
      drowning (FWD), 26 saltwater drowning (SWD), and 22 non-drowning cases as
      controls. Then, immunohistochemical study combined with morphometry was carried
      out in order to examine the differential expression of AQP1 and AQP4 in the brain
      samples. Immunohistochemically, star-shaped cells bearing highly branched
      processes, often surrounding blood vessels, showed positive reactions for AQP1
      and AQP4 in FWD, SWD, as well as control groups. Additionally, with double-color
      immunofluorescence analysis, AQP1- or AQP4-positive cells could be identified as
      GFAP-positive astrocytes. Moreover, AQP1-positive reaction was also observed in
      blood vessels. Morphometrically, there were no significant differences in AQP1
      expression in astrocytes or in blood vessels among the three groups. In contrast,
      the average value of AQP4-positive astrocytes was significantly higher in FWD
      cases than in SWD and control groups. Moreover, AQP4 expression was significantly
      lower in SWD than in the control group (p < 0.05). Moreover, there was no
      significant correlation between post-submerged interval and AQP expression in
      drowning cases. Therefore, immunohistochemical analysis of intracerebral AQP4
      expression would be forensically useful for differentiation between FWD and SWD.

PMID- 21069374
TI  - LINE-1 retrotransposition events affect endothelial proliferation and migration.
AB  - Long interspersed nuclear element-1 (LINE-1, L1) is a retrotransposon which
      affects the human genome by a variety of mechanisms. While LINE-1 expression is
      suppressed in the most somatic human cells, LINE-1 elements are activated in
      human cancer. Recently, high accumulation of LINE-1-encoded ORF1p and ORF2p in
      endothelial cells of mature human blood vessels was described. Here, we
      demonstrate that LINE-1 de novo retrotransposition events lead to a reduction of
      endothelial cell proliferation and migration in a porcine aortic endothelial
      (PAE) cell model. Cell cycle studies show a G0/G1 arrest in PAE cells harboring
      LINE-1 de novo retrotransposition events. Remarkably, in in situ analysis LINE-1
      encoded ORF2p was not detectable in tumor blood vessels of different human organs
      while vascular endothelial cells of corresponding normal organs strongly
      expressed LINE-1 ORF2p. Quantitative RT-PCR analysis revealed that LINE-1 de novo
      retrotransposition influences selectively the expression of some angiogenic
      factors such as VEGF and Tie-2. Thus, our data suggest that LINE-1 de novo
      retrotransposition events might suppress angiogenesis and tumor vascularisation
      by reducing the angiogenic capacity of vascular endothelial cells.

PMID- 21069375
TI  - Possible involvement of maspin in tooth development.
AB  - Maspin is a 42 kDa serine protease inhibitor that possesses tumor suppressive and
      anti-angiogenic activities. Despite of a huge amount of data concerning the
      expression pattern of maspin in various tissues and its relevance to the
      biological properties of a variety of human cancer cells, little is known on the
      maspin expression in skeletal and tooth tissues. Recently, we reported that
      maspin may play an important role in extracellular matrix formation in bone by
      enhancing the accumulation of latent TGF-beta in the extracellular matrix. This
      study was performed to elucidate the possible role of maspin in tooth
      development. First, an immunohistochemical analysis for human tooth germs at the
      late bell stage showed the expression of maspin by active ameloblasts and
      odontoblasts that were forming enamel and dentin, respectively. During rat tooth
      development, maspin expression was observed for the first time in inner and outer
      enamel epithelial cells and dental papilla cells at early bell stage. The
      neutralizing anti-maspin antibody inhibited the proper dental tissue formation in
      organ cultures of mandibular first molars obtained from 21-day-old rat embryos.
      In addition, the proliferation of HAT-7 cells, a rat odontogenic epithelial cell
      line, and human dental papilla cells were suppressed in a dose-dependent manner
      with anti-maspin antibody. Moreover, RT-PCR analysis showed that the expression
      of mRNA for tooth-related genes including dentin matrix protein 1, dentin
      sialophosphoprotein and osteopontin in human dental papilla cells was inhibited
      when treated with anti-maspin antibody. These findings suggest that maspin
      expressed in ameloblasts and odontoblasts plays an important physiological role
      in tooth development through the regulation of matrix formation in dental
      tissues.

PMID- 21069376
TI  - Small GTPases of the Rab family in the brain of Bombyx mori.
AB  - Small GTPases of the Rab family are key regulators of membrane trafficking. We
      produced antibodies against the Rab7 protein of Bombyx mori (BRab7) in rabbits,
      and against the Rab11 protein of B. mori (BRab11) in mice. The antibodies
      recognized BRab7 and BRab11 proteins, but did not recognize other Rab proteins.
      Immunoblotting of samples from brain tissue of B. mori revealed a single band for
      each antibody. Rab11 was expressed in most tissues, whereas Rab7 was expressed in
      the brain, ovary, and testis. Immunohistochemical reactivity of Rab7 and Rab11 in
      the brain of B. mori was restricted to neurons of the pars intercerebralis and
      dorsolateral protocerebrum. Double-labeling experiments demonstrated that
      immunohistochemical reactivity of Rab7 co-localized with that of Rab11 and
      partially with that of Rab8. Immunohistochemical reactivity of Rab11 and Rab8 co
      localized with that of PERIOD, one of the proteins associated with circadian
      rhythm. These findings suggest that Rab7, Rab8, and Rab11 are involved in protein
      transport in the neurons of the brain of B. mori and might play a role in the
      control of circadian rhythm.

PMID- 21069377
TI  - Oxidative stress, inflammation and recovery of muscle function after damaging
      exercise: effect of 6-week mixed antioxidant supplementation.
AB  - There is no consensus regarding the effects of mixed antioxidant vitamin C and/or
      vitamin E supplementation on oxidative stress responses to exercise and
      restoration of muscle function. Thirty-eight men were randomly assigned to
      receive either placebo group (n = 18) or mixed antioxidant (primarily vitamin C &
      E) supplements (n = 20) in a double-blind manner. After 6 weeks, participants
      performed 90 min of intermittent shuttle-running. Peak isometric torque of the
      knee flexors/extensors and range of motion at this joint were determined before
      and after exercise, with recovery of these variables tracked for up to 168 h post
      exercise. Antioxidant supplementation elevated pre-exercise plasma vitamin C (93
      +/- 8 MUmol l(-1)) and vitamin E (11 +/- 3 MUmol l(-1)) concentrations relative
      to baseline (P < 0.001) and the placebo group (P <= 0.02). Exercise reduced peak
      isometric torque (i.e. 9-19% relative to baseline; P <= 0.001), which persisted
      for the first 48 h of recovery with no difference between treatment groups. In
      contrast, changes in the urine concentration of F(2)-isoprostanes responded
      differently to each treatment (P = 0.04), with a tendency for higher
      concentrations after 48 h of recovery in the supplemented group (6.2 +/- 6.1 vs.
      3.7 +/- 3.4 ng ml(-1)). Vitamin C & E supplementation also affected serum
      cortisol concentrations, with an attenuated increase from baseline to the peak
      values reached after 1 h of recovery compared with the placebo group (P = 0.02)
      and serum interleukin-6 concentrations were higher after 1 h of recovery in the
      antioxidant group (11.3 +/- 3.4 pg ml(-1)) than the placebo group (6.2 +/- 3.8 pg
      ml(-1); P = 0.05). Combined vitamin C & E supplementation neither reduced markers
      of oxidative stress or inflammation nor did it facilitate recovery of muscle
      function after exercise-induced muscle damage.

PMID- 21069378
TI  - Enhanced systolic myocardial function in elite endurance athletes during combined
      arm-and-leg exercise.
AB  - The aim here was to employ color tissue velocity imaging (TVI), to test the
      hypothesis that highly trained endurance athletes exhibit enhanced systolic
      function of the left ventricular (LV) myocardium both at rest and during combined
      arm-and-leg exercise in comparison with untrained subjects. For each of the ten
      elite male (EG) and ten matched control participants (CG), LV dimensions and
      systolic function were assessed at rest using echocardiography. Subsequently,
      these subjects exercised continuously on a combined arm-and-leg cycle ergometer
      for 3 min each at 50, 60, 70, 80, 90 and 100% of VO(2max). Oxygen uptake, heart
      rate, systolic blood pressure (SBP) and peak contraction systolic velocities of
      the LV myocardium (PSV) were recorded in the end of each level. At rest, the
      trained and untrained groups differed with respect to LV dimensions, but not
      systolic function. At 60-100% VO(2max), the EG group demonstrated both higher PSV
      and SBP. The observation that the EG athletes had higher PSV than CG during
      exercise at 60-100% VO(2max), but not at rest or at 50% of VO(2max), suggested an
      enhanced systolic capacity. This improvement is likely to be due to an enhanced
      inotropic contractility, which only becomes apparent during exercise.

PMID- 21069379
TI  - Hyperoxia-induced alterations in cardiovascular function and autonomic control
      during return to normoxic breathing.
AB  - Hyperoxia causes hemodynamic alterations. We hypothesized that cardiovascular and
      autonomic control changes last beyond the end of hyperoxic period into normoxia.
      Ten healthy volunteers were randomized to breathe either medical air or 100%
      oxygen for 45 min in a double-blind study design. Measurements were performed
      before (baseline) and during gas exposure, and then 10, 30, 60, and 90 min after
      gas exposure. Hemodynamic changes were studied by Doppler echocardiography.
      Changes in cardiac and vasomotor autonomic control were evaluated through changes
      in spectral power of heart rate variability and blood pressure variability.
      Cardiac baroreflex sensitivity was assessed by the sequence method. Hyperoxia
      significantly decreased heart rate and increased the high frequency power of
      heart rate variability, suggesting a chemoreflex increase in vagal activity since
      the slope of cardiac baroreflex was significantly decreased during hyperoxia.
      Hyperoxia increased significantly the systemic vascular resistances and decreased
      the low frequency power of blood pressure variability, suggesting that hyperoxic
      vasoconstriction was not supported by an increase in vascular sympathetic
      stimulation. These changes lasted for 10 min after hyperoxia (p < 0.05). After
      the end of hyperoxic exposure, the shift of the power spectral distribution of
      heart rate variability toward a pattern of increased cardiac sympathetic activity
      lasted for 30 min (p < 0.05), reflecting a resuming of baseline autonomic
      balance. Cardiac output and stroke volume were significantly decreased during
      hyperoxia and returned to baseline values (10 min) later than heart rate. In
      conclusion, hyperoxia effects continue during return to normoxic breathing, but
      cardiac and vascular parameters followed different time courses of recovery.

PMID- 21069380
TI  - Cardiac function and arteriovenous oxygen difference during exercise in obese
      adults.
AB  - The purpose of this study was to assess cardiac function and arteriovenous oxygen
      difference (a-vO(2) difference) at rest and during exercise in young, normal
      weight (n = 20), and obese (n = 12) men and women who were matched for age and
      fitness level. Participants were assessed for body composition, peak oxygen
      consumption (VO(2peak)), and cardiac variables (thoracic bioimpedance)-cardiac
      index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection
      fraction (EF)-at rest and during cycling exercise at 65% of VO(2peak).
      Differences between groups were assessed with multivariate ANOVA and mixed-model
      ANOVA with repeated measures controlling for sex. Absolute VO(2peak) and
      VO(2peak) relative to fat-free mass (FFM) were similar between normal-weight and
      obese groups (Mean +/- SEE 2.7 +/- 0.2 vs. 3.3 +/- 0.3 l min(-1), p = 0.084 and
      52.4 +/- 1.5 vs. 50.9 +/- 2.3 ml kg FFM(-1) min(-1), p = 0.583, respectively). In
      the obese group, resting Q and SV were higher (6.7 +/- 0.4 vs. 4.9 +/- 0.1 l min(
      1), p < 0.001 and 86.8 +/- 4.3 vs. 65.8 +/- 1.9 ml min(-1), p < 0.001,
      respectively) and EF lower (56.4 +/- 2.2 vs. 65.5 +/- 2.2%, p = 0.003,
      respectively) when compared with the normal-weight group. During submaximal
      exercise, the obese group demonstrated higher mean CI (8.8 +/- 0.3 vs. 7.7 +/-
      0.2 l min(-1) m(-2), p = 0.007, respectively), Q (19.2 +/- 0.9 vs. 13.1 +/- 0.3 l
      min(-1), p < 0.001, respectively), and SV (123.0 +/- 5.6 vs. 88.9 +/- 4.1 ml min(
      1), p < 0.001, respectively) and a lower a-vO(2) difference (10.4 +/- 1.0 vs.
      14.0 +/- 0.7 ml l00 ml(-1), p = 0.002, respectively) compared with controls. Our
      study suggests that the ability to extract oxygen during exercise may be impaired
      in obese individuals.

PMID- 21069381
TI  - Safety and efficacy of early postoperative hyperbaric oxygen therapy with
      restriction of transfusions in patients with HCC who have undergone partial
      hepatectomy.
AB  - BACKGROUND: Recent studies have shown that intraoperative blood loss and blood
      transfusions promote postoperative recurrence of hepatocellular carcinoma (HCC).
      Hyperbaric oxygen therapy (HBOT) is a specific method of oxygen administration,
      which is independent of fluid therapy or blood transfusion. The aim of the
      present study was to assess the usefulness of acute HBOT after liver resection
      for patients with HCC in order to minimize the requirement for perioperative
      blood transfusions. PATIENTS AND METHODS: Forty-one consecutive patients who
      showed Hb level < 9.0 mg/dl at the end of hepatic resection were randomly
      assigned to a control group (n = 21) or an HBOT group (n = 20). HBOT at 2.0 atm.
      with inhalation of 100% oxygen for a duration of 60 min was performed at 3, 24,
      and/or 48 h after the end of the hepatectomy. Regarding postoperative hepatic
      hemodynamics, liver function tests, and outcome data, prospective comparisons
      were completed in both groups. The two groups of patients were similar with
      respect to results from preoperative assessments. RESULTS: In six patients from
      the HBOT group, who experienced intraoperative major bleeding or showed fatal
      hepatic hypoxia (ShvO(2) < 50%), the levels of ShvO(2) and serum lactate were
      significantly improved after HBOT. When compared to the control group, the HBOT
      group showed better changes of ShvO(2), serum lactate, and bilirubin levels for
      the first 3 postoperative days following surgery. Additionally, the HBOT group
      did not experience any fatal complications and had a lower incidence of
      postoperative hyperbilirubinemia than the control group. We also observed that
      postoperative NK cell activity and cancer-free survival in the HBOT group tended
      to be better than in the control group, although the differences did not reach
      significance. CONCLUSION: These results suggest that acute HBOT after
      hepatectomy, aimed at reducing perioperative erythrocyte transfusions, may be
      employed for overcoming deficiencies in systemic and hepatic oxygen supply and
      thus diminishing postoperative complications. As an added benefit, such therapy
      may affect postoperative immunological responses and long-term survival after
      liver resection in HCC patients. Further analyses of the use of HBOT is warranted
      to confirm surgical outcome data and to assess the economic impact on healthcare
      costs.

PMID- 21069382
TI  - Proximal acid reflux treated by fundoplication predicts a good outcome for
      chronic cough attributable to gastro-oesophageal reflux disease.
AB  - PURPOSE: The aim for this study is to examine whether proximal, as opposed to
      distal, oesophageal reflux predicts a good outcome after fundoplication in
      patients with suspected acid-induced chronic cough. METHOD: Between 1999 and
      2007, 81 patients with refractory chronic cough underwent manometry and dual
      probe pH studies. In 59 patients, pathological reflux was confirmed, and 21 of
      these underwent laparoscopic fundoplication by a single surgeon. Proximal reflux
      was defined as an upper channel time pH <4 of >1.4%. The Chi-square test and Mann
      Whitney U test were used in the statistical analysis. RESULTS: All patients with
      heartburn had their symptoms abolished by surgery. The proximal extent of reflux
      predicted cough improvement. Eleven of 14 patients with proven proximal reflux
      had complete symptom relief from surgery as opposed to two of seven with distal
      only reflux (Chi-square = 4.95; degrees of freedom = 1; p = 0.026). There was no
      correlation between oesophageal motility (as assessed by per cent abnormal wet
      swallows) and pathological reflux on outcome of surgery. Correlation of episodes
      of coughing with episodes of proximal or distal reflux was poor and had no useful
      predictive value. CONCLUSION: Patients with refractory chronic cough are
      significantly more likely to benefit from surgery if their pH study shows an
      upper channel pH time >1%.

PMID- 21069383
TI  - miRNA expression patterns of Triticum dicoccoides in response to shock drought
      stress.
AB  - Drought is a major environmental stress factor that affects plant growth and
      development worldwide. Wild emmer wheat (Triticum turgidum ssp. dicoccoides), the
      ancestor of domesticated durum wheat (Triticum turgidum ssp. durum), has great
      potential for improving the understanding of the wheat drought response.
      MicroRNAs (miRNAs) are a recently discovered class of gene expression regulators
      that have also been linked to several plant stress responses; however, this
      relationship is just beginning to be understood. miRNA expression patterns of
      drought-resistant wild emmer wheat in response to drought stress were
      investigated using a plant miRNA microarray platform. Expression was detected to
      be 205 miRNAs in control and 438 miRNAs in drought-stressed leaf and root
      tissues. Of these miRNAs, the following 13 were differentially regulated in
      response to drought: miR1867, miR896, miR398, miR528, miR474, miR1450, miR396,
      miR1881, miR894, miR156, miR1432, miR166 and miR171. Regulation of miRNAs upon 4
      and 8 h drought stress applications observed by qRT-PCR. Target transcripts of
      differentially regulated miRNAs were computationally predicted. In addition to
      miRNA microarray study, five new conserved T. turgidum miRNAs were identified
      through a homology-based approach, and their secondary structures and putative
      targets were predicted. These findings both computationally and experimentally
      highlight the presence of miRNAs in T. dicoccoides and further extend the role of
      miRNAs under shock drought stress conditions.

PMID- 21069386
TI  - Reconstructing the pollinator community and predicting seed set from hydrocarbon
      footprints on flowers.
AB  - The measurement of insect visits to flowers is essential in basic and applied
      pollination ecology studies but often fraught with difficulty. Floral visitation
      is highly variable, and observational studies are limited in scope due to the
      considerable time necessary to acquire reliable data. The aim of our study was to
      investigate whether the analysis of hydrocarbon residues (footprints) deposited
      by insects during flower visits would allow reconstruction of the visitor
      community and prediction of seed set for large numbers of plants. In 3
      consecutive years, we recorded bumblebee visitation to wild plants of comfrey,
      Symphytum officinale, and later used gas chromatography/mass spectrometry (GC/MS)
      to quantify bumblebee-derived unsaturated hydrocarbons (UHCs) extracted from
      flowers. We found that the UHCs washed from corollas were most similar to the
      tarsal UHC profile of the most abundant bumblebee species, Bombus pascuorum, in
      all 3 years. The species composition of the bumblebee communities estimated from
      UHCs on flowers were also similar to those actually observed. There was a
      significant positive correlation between the observed number of visits by each of
      three bumblebee species (contributing 3-68% of flower visits) and the estimated
      number of visits based on UHC profiles. Furthermore, significant correlations
      were obtained separately for workers and drones of two of the study species. Seed
      set of comfrey plants was positively correlated to overall bumblebee visitation
      and the total amount of UHCs on flowers, suggesting the potential for pollen
      limitation. We suggest that quantifying cumulative footprint hydrocarbons
      provides a novel way to assess floral visitation by insects and can be used to
      predict seed set in pollen-limited plants.

PMID- 21069384
TI  - Current advances in understanding of immunopathology of atherosclerosis.
AB  - The importance of the involvement of the immune system in the development and
      progression of atherosclerosis was first suggested after the discovery of T cells
      in atherosclerotic lesions in 1990s. In order to be activated, T cell needs to be
      presented with an antigen but how this occurs in atherosclerosis has been unclear
      until recently. Current research has recognised dendritic cells as key initiators
      and regulators of immune processes in atherosclerosis. Accumulating evidence has
      revealed novel functions of several subsets of regulatory T cells, which have
      been shown to maintain immunological tolerance to self-antigens and to inhibit
      atherosclerosis development by suppressing the inflammatory response of effector
      T cells. Recent studies have also revealed the importance of natural killer T
      cells and their interaction with dendritic cells in atherogenesis. This review
      briefly summarises recent advances in the understanding of immune mechanisms in
      atherosclerosis and highlights the perspective of immunisation as an approach
      against this disease.

PMID- 21069385
TI  - Characteristics of triple-negative breast cancer.
AB  - BACKGROUND: Triple-negative breast cancers (TNBC) neither express hormone
      receptors, nor overexpress HER2. They are associated with poor prognosis, as
      defined by low five-year survival and high recurrence rates after adjuvant
      therapy. Overall, TNBC share striking similarities with basal-like breast cancers
      (BBC), so a number of studies considered them being the same. The purpose of this
      review is to summarise the latest findings on TNBC concerning its relation and
      delineation to BBC, discuss the developmental pathways involved and address
      clinical implications for this complex type of breast cancer. METHODS: The recent
      literature from PubMed and Medline databases was reviewed. RESULTS: Not all TNBC
      are of the intrinsic BBC subtype (nonbasal (NB)-TNBC), nor are all BBC triple
      negative (non-triple-negative (NTN)-BBC). There is increasing evidence that a
      triple-negative, basal-like breast cancer (TNBBC) subtype develops mainly through
      a BRCA1-related pathway. Somatic mutations that contribute to NTN-BBC and NB-TNBC
      development are possibly not related to this pathway, but may occur randomly due
      to increased genomic instability in these tumours. Several therapeutic options
      exist for TNBBC, which exhibited promising results in recent clinical trials.
      Cytotoxic therapies, e.g. combined treatment with anthracyclines or taxanes,
      achieved good tumour regression rates in the neo-adjuvant setting, but also
      showed considerable recurrence during the first 5 years after therapy. Targeted
      therapy options involve PARP1 and EGFR inhibition, although both approaches still
      need further investigation. CONCLUSIONS: TNBC and BBC are not the same disease
      entity. The TNBBC subtype shows the largest homogeneity in terms of tumour
      development, prognosis and clinical intervention options.

PMID- 21069387
TI  - Control of alpha-amylase production by Bacillus subtilis.
AB  - This study proposes two adaptive control algorithms for the fed-batch production
      of alpha-amylase. The first one uses online information from hardware measuring
      glucose. Online information of both biomass and glucose concentrations measured
      with different frequency is used in the second algorithm. Hardware measuring
      variables are inputs for software sensors of glucose concentration and (specific)
      glucose consumption rate. Either of the algorithms do not require any kinetic
      coefficients. This is a benefit, because the kinetic coefficients can vary during
      cultivation and between cultivations, leading to low process reproducibility and
      the non-stationary state of the bioprocess. The results of simulation
      investigations show good performance of the proposed control schemes.

PMID- 21069388
TI  - Evaluating the structural properties of suprahyoid muscles and their potential
      for moving the hyoid.
AB  - Superior and anterior hyoid movements are important events in pharyngeal
      deglutition. This cross-sectional study uses a cadaver model to document the
      structural properties of the muscles underlying these movements in an effort to
      understand how their morphology influences function. Measurements to determine
      physiological cross-sectional areas (PCSAs) of swallowing muscles were taken from
      hemisected head and neck formalin-fixed cadaver specimens (n = 13). Coordinates
      of muscle attachment sites and PCSAs were used to calculate i and j unit force
      vectors, where i and j represent anterior-posterior and superior-inferior
      directions, respectively. The suprahyoid muscle subsamples were grouped for
      analysis as follows: digastric (DG), geniohyoid (GH), mylohyoid (MH), and
      stylohyoid (SH). The ANOVA with Tukey HSD post hoc analysis of unit force vectors
      showed the following results: GH (-0.44 +/- 0.15 cm(2)) >MH (-0.02 +/- 0.21
      cm(2)), DG (-0.05 +/- 0.11 cm(2)), SH (0.14 +/- 0.04 cm(2)), with negative values
      representing the anterior direction (p < 0.01); and MH (0.91 +/- 0.28 cm(2)) >DG
      (0.29 +/- 0.14 cm(2)), SH (0.22 +/- 0.08 cm(2)), GH (12 +/- 0.08 cm(2)), with
      positive values representing the superior direction (p < 0.01). The morphology of
      the suprahyoid muscles suggests that based on structural properties, the
      geniohyoid has the most potential to displace the hyoid in the anterior direction
      and the mylohyoid has the most potential to displace the hyoid in the superior
      direction. These data in complement with physiological findings may provide
      greater insight into these movements for those developing novel treatments for
      dysphagia.

PMID- 21069390
TI  - Localisation pattern of homogalacturonan and arabinogalactan proteins in
      developing ovules of the gymnosperm plant Larix decidua Mill.
AB  - We have identified and characterised the temporal and spatial distribution of the
      homogalacturonan (HG) and arabinogalactan proteins (AGP) epitopes that are
      recognised by the antibodies JIM5, JIM7, LM2, JIM4, JIM8 and JIM13 during ovule
      differentiation in Larix decidua Mill. The results obtained clearly show
      differences in the pattern of localisation of specific HG epitopes between
      generative and somatic cells of the ovule. Immunocytochemical studies revealed
      that the presence of low-esterified HG is characteristic only of the wall of
      megasporocyte and megaspores. In maturing female gametophytes, highly esterified
      HG was the main form present, and the central vacuole of free nuclear
      gametophytes was particularly rich in this category of HG. This pool will
      probably be used in cell wall building during cellularisation. The selective
      labelling obtained with AGP antibodies indicates that some AGPs can be used as
      markers for gametophytic and sporophytic cells differentiation. Our results
      demonstrated that the AGPs recognised by JIM4 may constitute molecules
      determining changes in ovule cell development programs. Just after the end of
      meiosis, the signal detected with JIM4 labelling appeared only in functional and
      degenerating megaspores. This suggests that the antigens bound by JIM4 are
      involved in the initiation of female gametogenesis in L. decidua. Moreover, the
      analysis of AGPs distribution showed that differentiation of the nucellus cells
      occurs in the very young ovule stage before megasporogenesis. Throughout the
      period of ovule development, the pattern of localisation of the studied AGPs was
      different both in tapetum cells surrounding the gametophyte and in nucellus
      cells. Changes in the distribution of AGPs were also observed in the nucellus of
      the mature ovule, and they could represent an indicator of tissue arrangement to
      interact with the growing pollen tube. The possible role of AGPs in fertilisation
      is also discussed.

PMID- 21069389
TI  - Serum cystatin C for estimation of residual renal function in children on
      peritoneal dialysis.
AB  - Residual renal function (RRF) is an important parameter in the management of
      patients on chronic dialysis. The aim of this cross-sectional study was to
      determine the efficacy of serum cystatin C (CysC) for RRF estimation in 20
      children (16 boys, 4 girls; median age 13.4 years) undergoing peritoneal dialysis
      (PD). For studies of correlation with serum CysC, the average of creatinine
      clearance rate (Ccr) and urea clearance rate (Curea), Kt/Vurea, and weekly Ccr
      were evaluated as parameters reflecting RRF. The serum CysC level was found to be
      negatively correlated with urine volume (r=-0.717, P<0.001), average of Ccr and
      Curea (r=-0.851, P<0.001), total and renal weekly Ccr (r=-0.795, P<0.001; r=
      0.845, P<0.001, respectively), and renal Kt/Vurea (r=-0.793, P<0.001) and
      positively correlated with peritoneal weekly Ccr (r=0.738, P<0.001) and
      peritoneal Kt/Vurea (r=0.785, P<0.001). There was no significant association with
      total Kt/Vurea (r=-0.335, P=0.148). In non-anuric group of patients, serum CysC
      had no link to peritoneal Kt/Vurea (r=0.573, P=0.066), but was negatively
      correlated with renal Kt/Vurea (r=-0.609, P=0.047). In the multiple regression
      analysis, renal Kt/Vurea significantly contributed to log CysC concentration
      rather than peritoneal Kt/Vurea. The results of this study suggest that serum
      CysC could be an appropriate marker for RRF, independent of total and peritoneal
      Kt/Vurea.

PMID- 21069391
TI  - Down regulation of trophic factors in neonatal rat spinal cord after
      administration of cerebrospinal fluid from sporadic amyotrophic lateral sclerosis
      patients.
AB  - Accumulating evidence supports neuroprotective role of trophic factors in
      amyotrophic lateral sclerosis (ALS). Previous studies from our laboratory report
      that the CSF of patients with sporadic ALS (ALS-CSF) induces degenerative changes
      in the rat spinal motor neurons and reactive astrogliosis in the surrounding gray
      matter. The present study was aimed to investigate if the ALS-CSF affected the
      expression of trophic factors namely, brain-derived neurotrophic factor (BDNF),
      fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1) in the
      newborn rat spinal cords. ALS-CSF was intrathecally injected into the neonatal
      rats and the mRNA levels of the trophic factors were determined by quantitative
      real-time polymerase chain reaction. Here, we report significant down regulation
      in the gene expression of trophic factors for BDNF, FGF2 and IGF1. BDNF mRNA
      levels were found to be reduced by 6.8-fold in the ALS-CSF injected group
      compared to control groups. The levels of IGF1 and FGF2 mRNA were also decreased
      by 3.91- and 2.13-fold, respectively, in the ALS group. We further found that
      exogenous supplementation of BDNF considerably reduced the aberrant
      phosphorylation of neurofilaments, complementing our earlier findings of restored
      expression of voltage gated sodium channel. Reduced expression of trophic factors
      indicates an altered microenvironment of the motor neurons and could possibly be
      one of the contributing factors in the degeneration process.

PMID- 21069392
TI  - Increased expression of beta amyloid precursor gene in the hippocampus of
      streptozotocin-induced diabetic mice with memory deficit and anxiety induction.
AB  - Diabetes has been associated with memory and behavioral dysfunctions such as
      anxiety. However, exact mechanisms of how diabetes affect such changes remain to
      be characterized. The purpose of present study is to search for streptozotocin
      regulated genes in hippocampus of the mice using a differential display PCR
      technique, in the hope of type I diabetes-related hippocampal gene(s). It has
      been found that expression of a PCR product was increased by streptozotocin
      treatment and it was identified as beta amyloid precursor protein. These results
      were further confirmed by performing RT-PCR analysis. In addition, the protein
      expression of beta amyloid precursor protein as evidenced by Western blot
      analysis was increased in the hippocampus of streptozotocin-induced diabetic
      mice. To explore if the changes in amyloid beta precursor protein could be
      related with functional changes in the brain regarding memory activity and
      anxiety, passive avoidance test and elevated plus maze test were performed,
      respectively. There is significant reduction of memory formation and marked
      induction of anxiety in the streptozotocin-induced diabetic mice. These results
      suggest that increase of beta amyloid precursor protein may play a role in the
      memory loss and anxiety induction in type I diabetic mice.

PMID- 21069393
TI  - Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease.
AB  - The need for an early and differential diagnosis of Parkinson's disease (PD) is
      undoubtedly one of the main quests of the century. An early biomarker would
      enable therapy to begin sooner and would, hopefully, slow or better prevent
      progression of the disease. We performed transcript profiling via quantitative RT
      PCR in RNA originating from peripheral blood samples. The groups were de novo (n
      = 11) and medicated PD (n = 94) subjects and healthy controls (n = 34), while for
      negative control Alzheimer's disease (AD; n = 14) subjects were recruited as an
      additional neurodegenerative disease. The results were retested on a second
      recruitment consisting 22 medicated PD subjects versus 33 controls and 12 AD.
      Twelve transcripts were chosen as candidate genes, according to previous
      postmortem brain profiling. Multiple analyses resulted in four significant genes:
      proteasome (prosome, macropain) subunit-alpha type-2 (PSMA2; p = 0.0002, OR =
      1.15 95% CI 1.07-1.24), laminin, beta-2 (laminin S) (LAMB2; p = 0.0078, OR = 2.26
      95% CI 1.24-4.14), aldehyde dehydrogenase 1 family-member A1 (ALDH1A1; p = 0.016,
      OR = 1.05 95% CI 1.01-1.1), and histone cluster-1 H3e (HIST1H3E; p = 0.03, OR =
      0.975 95% CI 0.953-0.998) differentiating between medicated PD subjects versus
      controls. Using these four biomarkers for PD diagnosis, we achieved sensitivity
      and specificity of more than 80%. These biomarkers might be specific for PD
      diagnosis, since in AD subjects no significant results were observed. In the
      second validation, three genes (PSMA2, LAMB2 and ALDH1A1) demonstrated high
      reproducibility. This result supports previous studies of gene expression
      profiling and may facilitate the development of biomarkers for early diagnosis of
      PD.

PMID- 21069394
TI  - Molecular characterization of avian astroviruses.
AB  - Astroviruses are frequently associated with enteric diseases in poultry, being
      isolated from cases of runting-stunting syndrome (RSS) of broiler chickens, poult
      enteritis complex (PEC), and poult enteritis mortality syndrome (PEMS) of
      turkeys. Currently, five types of avian astrovirus have been identified: turkey
      astroviruses 1 and 2 (TAstV-1, TAstV-2), avian nephritis virus (ANV), chicken
      astrovirus (CAstV) and duck astrovirus (DAstV). The objective of this study was
      to molecularly characterize the different types of avian astroviruses circulating
      in commercial poultry. Sequence analysis of a region of ORF2, which encodes the
      capsid precursor protein associated with serotype and viral pathogenesis,
      revealed extensive variation in amino acid sequence within each subtype: TAstV-2
      (81.5%-100%), ANV (69.9%-100%), and CAstV (85.3%-97.9%). However, this region was
      more conserved in TAstV-1's (96.2%-100%). Furthermore, a novel astrovirus was
      detected in chicken samples and found to be <64% similar to ANV and <30.6%
      similar to CAstV. The results of this study underline the great genetic
      variability of avian astroviruses and indicate that there are most likely
      multiple serotypes of each avian astrovirus circulating in commercial poultry.

PMID- 21069395
TI  - Analysis of codon usage in bovine viral diarrhea virus.
AB  - Bovine viral diarrhea virus (BVDV) is a widespread virus in beef and dairy herds.
      BVDV has been grouped into two genotypes, genotype 1 and genotype 2. In this
      study, the relative synonymous codon usage (RSCU) values, effective number of
      codon (ENC) values and nucleotide content were investigated, and a comparative
      analysis of codon usage patterns for open reading frames (ORFs) of 22 BVDV
      genomes, including 14 of genotype 1 and 8 of genotype 2, was carried out. A high
      A+U content and low codon bias were found in BVDV genomes. Depending on the RSCU
      data, it was found that there was a significant variation in bias of codon usage
      between the two genotypes, and a geographic factor exists only in genotype-1 of
      BVDV. The RSCU data have a negative correlation with general average
      hydrophobicity (GRAVY), aromaticity and nucleotide content. Furthermore, the
      overall abundance of C and U has no effect on the synonymous codon usage
      patterns. In contrast, the A and G content showed a significant correlation with
      the nucleotide content at the third position. In addition, the codon usage
      patterns of BVDV are similar to those of 22 conserved genes of Bos taurus. Taken
      together, the genetic characteristics of BVDV possibly result from interactions
      between natural selection and mutation pressure.

PMID- 21069396
TI  - The African swine fever virus lectin EP153R modulates the surface membrane
      expression of MHC class I antigens.
AB  - We have modeled a 3D structure for the C-type lectin domain of the African swine
      fever virus protein EP153R, based on the structure of CD69, CD94 and Ly49A cell
      receptors, and this model predicts that a dimer of EP153R may establish an
      asymmetric interaction with one MHC-I molecule. A functional consequence of this
      interaction could be the modulation of MHC-I expression. By using both
      transfection and virus infection experiments, we demonstrate here that EP153R
      inhibits MHC-I membrane expression, most probably by impairing the exocytosis
      process, without affecting the synthesis or glycosylation of MHC antigens.
      Interestingly, the EP153-mediated control of MHC requires the intact
      configuration of the lectin domain of the viral protein, and specifically the
      R133 residue. Interference of EP153R gene expression during virus infection and
      studies using virus recombinants with the EP153R gene deleted further support the
      inhibitory role of the viral lectin on the expression of MHC-I antigens.

PMID- 21069397
TI  - Synthesis of biodegradable chiral poly(ester-imide)s derived from valine-,
      leucine- and tyrosine-containing monomers.
AB  - The present demand for a drastic reduction in environmental pollution is extended
      to qualitative change in the approach to development of biodegradable polymers.
      The aim of this article is to focus on the synthesis of biodegradable optically
      active poly(ester-imide)s (PEI)s, which compose of different amino acids in the
      main chain as well as in the side chain. These polymers were synthesized by
      polycondensation of diacid monomers such as 5-(2-phthalimidyl-3-methyl
      butanoylamino) isophthalic acid (1), 5-(4-methyl-2-phthalimidyl
      pentanoylamino)isophthalic acid (2) with N,N'-(pyromellitoyl)-bis-L: -tyrosine
      dimethyl ester (3) as a phenolic diol. The direct polycondensation reaction was
      carried out in a system of tosyl chloride, pyridine and N,N-dimethylformamide as
      a condensing agent under conventional heating conditions. The optically active
      PEIs were obtained in good yield and moderate inherent viscosity. The synthesized
      polymers were characterized by means of FT-IR, (1)H-NMR, elemental and thermo
      gravimetric analysis techniques. In addition, in vitro toxicity and soil burial
      test were employed for assessing the sensitivity of these compounds to microbial
      degradation. To this purpose, biodegradability behavior of the monomers and
      polymers were investigated in culture media and soil condition. The results of
      this study revealed that synthesized monomers and their derived polymers are
      biologically active and probably microbiologically biodegradable.

PMID- 21069398
TI  - Synthetic strategy for side chain mono-N-alkylation of Fmoc-amino acids promoted
      by molecular sieves.
AB  - A new synthetic strategy to alkylate amino groups under mild conditions has been
      developed. It utilizes only 4 A molecular sieves as base in order to promote the
      N-alkylation reaction, in presence of the appropriate alkyl halide. The
      methodology was validated by the simple and efficient side-chain N-alkylation of
      o-Ns-protected Fmoc-amino acid. One of them was introduced as building block into
      a peptide sequence, thus allowing the preparation of site-specific alkylated
      peptide molecules.

PMID- 21069399
TI  - A first partial Aplysia californica proteome.
AB  - Aplysia proteins have not been studied systematically and it was therefore the
      aim of the study to carry out protein profiling in ganglia from Aplysia
      californica (AC). AC ganglia were extirpated, proteins extracted and run on 2DE
      with subsequent in-gel digestion, followed by identification of proteins by nano
      LC-ESI-MS/MS on an ion trap. Proteins were identified based upon a public Aplysia
      EST database. Out of 408 picked spots, 276 spots were identified corresponding to
      172 ESTs and 118 individual proteins. The range of sequence coverage was between
      14 and 80% and the average amount of peptides used for the identification of
      proteins was 9 (from 3 to 24). Mean score for protein identification was 516.
      Comparison of protein levels between cerebral, pleural, pedal and abdominal
      ganglia revealed a series of significant differences including: signaling,
      metabolism, cytoskeleton and structural, redox, chaperone,
      replication/transcription and electron/proton transport proteins. The generation
      of a protein map complements transcriptional studies carried out in AC ganglia.
      The findings provide the basis for investigation into post-translational
      modifications, splice variants and assist in the generation of antibodies against
      AC proteins. Moreover, differences in protein expression between ganglia may be
      valuable for the design of future studies in neurobiology of AC.

PMID- 21069400
TI  - Proteomic analysis of apoptosis induction in human lung cancer cells by
      recombinant MVL.
AB  - Lung cancer is still difficult to treat by current chemotherapeutic procedures.
      We recently found that MVL, an anti-HIV lectin from blue-green algae Microcystis
      viridis, also has antitumor activity. The objective of this study was to
      investigate apoptosis-inducing activity of recombinant MVL (R-MVL) and proteomic
      changes in A549 cells, and to identify the molecular pathways responsible for the
      anti-cancer action of R-MVL. We found that R-MVL induces A549 cells apoptosis in
      a dose-dependent manner by using MTT assay, fluorescent microscope (FM) and flow
      cytometry (FCM), and the IC50 was calculated to be 24.12 MUg/ml. Subsequently, 7
      altered proteins in R-MVL-treated A549 cells were identified, including
      upregulated aldehyde dehydrogenase 1 and beta-actin, and five downregulated
      proteins: heat shock protein 90, heat shock 60, plastin 3, tropomyosin 3, and
      beta-tubulin. Further bioinformatics analysis predicted the potential pathways
      for R-MVL to induce apoptosis of A549 cells. In conclusion, this is the first
      report to investigate anti-cancer activity of R-MVL and its mechanism of action
      by proteomics analysis. Our observations provide potential therapeutic targets
      for lung cancer inhibitor intervention and implicated the development of novel
      anti-cancer therapeutic strategies.

PMID- 21069401
TI  - The essential role of the Cu(II) state of Sco in the maturation of the Cu(A)
      center of cytochrome oxidase: evidence from H135Met and H135SeM variants of the
      Bacillus subtilis Sco.
AB  - Sco is a red copper protein that plays an essential yet poorly understood role in
      the metalation of the Cu(A) center of cytochrome oxidase, and is stable in both
      the Cu(I) and Cu(II) forms. To determine which oxidation state is important for
      function, we constructed His135 to Met or selenomethionine (SeM) variants that
      were designed to stabilize the Cu(I) over the Cu(II) state. H135M was unable to
      complement a scoDelta strain of Bacillus subtilis, indicating that the His to Met
      substitution abrogated cytochrome oxidase maturation. The Cu(I) binding
      affinities of H135M and H135SeM were comparable to that of the WT and 100-fold
      tighter than that of the H135A variant. The coordination chemistry of the H135M
      and H135SeM variants was studied by UV/vis, EPR, and XAS spectroscopy in both the
      Cu(I) and the Cu(II) forms. Both oxidation states bound copper via the S atoms of
      C45, C49 and M135. In particular, EXAFS data collected at both the Cu and the Se
      edges of the H135SeM derivative provided unambiguous evidence for
      selenomethionine coordination. Whereas the coordination chemistry and copper
      binding affinity of the Cu(I) state closely resembled that of the WT protein, the
      Cu(II) state was unstable, undergoing autoreduction to Cu(I). H135M also reacted
      faster with H(2)O(2) than WT Sco. These data, when coupled with the complete
      elimination of function in the H135M variant, imply that the Cu(I) state cannot
      be the sole determinant of function; the Cu(II) state must be involved in
      function at some stage of the reaction cycle.

PMID- 21069402
TI  - Cyanobacteria and chloroflexi-dominated hypolithic colonization of quartz at the
      hyper-arid core of the Atacama Desert, Chile.
AB  - Quartz stones are ubiquitous in deserts and are a substrate for hypoliths,
      microbial colonists of the underside of such stones. These hypoliths thrive where
      extreme temperature and moisture stress limit the occurrence of higher plant and
      animal life. Several studies have reported the occurrence of green hypolithic
      colonization dominated by cyanobacteria. Here, we describe a novel red hypolithic
      colonization from Yungay, at the hyper-arid core of the Atacama Desert in Chile.
      Comparative analysis of green and red hypoliths from this site revealed markedly
      different microbial community structure as revealed by 16S rRNA gene clone
      libraries. Green hypoliths were dominated by cyanobacteria (Chroococcidiopsis and
      Nostocales phylotypes), whilst the red hypolith was dominated by a taxonomically
      diverse group of chloroflexi. Heterotrophic phylotypes common to all hypoliths
      were affiliated largely to desiccation-tolerant taxa within the Actinobacteria
      and Deinococci. Alphaproteobacterial phylotypes that affiliated with nitrogen
      fixing taxa were unique to green hypoliths, whilst Gemmatimonadetes phylotypes
      occurred only on red hypolithon. Other heterotrophic phyla recovered with very
      low frequency were assumed to represent functionally relatively unimportant taxa.

PMID- 21069403
TI  - Expression and characterization of a novel mesophilic protease from metagenomic
      library derived from Antarctic coastal sediment.
AB  - A metagenomic cosmid library was constructed, in which the insert DNA was derived
      from the coastal sediment near Antarctic China Zhongshan Station. One clone
      (ACPRO001) expressing protease activity was isolated from the library using milk
      agar plates. Sequencing of the clone revealed a novel protease gene. The amino
      acid sequence comparison and phylogenetic analysis indicated that it could be
      classified as a subtilisin-like serine protease, though the highly conserved
      residue Asp was replaced by Ala. The ACPRO001 protease gene was expressed in pET
      His and purified for characterization. The optimal temperature and pH for the
      activity of the ACPRO001 protease were 60 degrees C and pH 9.0, respectively. The
      enzyme retained about 73% of residual activity after 2 h incubation at 50 degrees
      C in the presence of Ca(2+). The presence of Ca(2+) increased the thermostability
      of ACPRO001 protease obviously. The enzymatic activity was inhibited by 1 mM
      phenylmethyl sulfonylfluoride (PMSF) and hydrochloride 4-(2-aminoethyl)
      benzenesulfonyl fluoride (AEBSF), indicating that it was a serine protease.

PMID- 21069404
TI  - The use of ID migraineTM questionnaire in patients with multiple sclerosis.
AB  - Primary headaches are underdiagnosed and undertreated in patients with multiple
      sclerosis (MS). The aim of our study was to investigate the possibility of using
      the ID migraineTM (ID-M) questionnaire to make a first-line diagnosis of migraine
      in subjects affected by MS. We consecutively recruited 144 patients regularly
      attending the MS Centre of S. Andrea Hospital in Rome. Results from ID-M were
      matched with diagnoses of a blind neurologist. According to the ICHD-II criteria,
      77 (53.5%) patients were diagnosed as suffering from migraine. ID-M showed high
      sensitivity (91%) and specificity (94%) in identifying patients with migraine. ID
      M was also able to discriminate patients affected by headache following
      interferon beta therapy, having only the 10% out of these patients a positive ID
      M. The use of the ID-M as a screening test is warranted not only in the
      epidemiological research, but also to ensure a better clinical management of
      patients with MS.

PMID- 21069405
TI  - Prospective study of telephone calls to a hotline for infectious disease
      consultation: analysis of 7,863 solicited consultations over a 1-year period.
AB  - To respond to the increasing requests of non-infectious disease physicians for
      access to infectious diseases expertise, a hotline was created in the infectious
      diseases consultation (IDC) unit of the Grenoble university-affiliated hospital
      (GUH). This study describes the patterns of solicited consultations provided by
      the hotline during a 1-year period. We conducted a prospective study of
      consecutive solicited IDCs requested by physicians in 2008. A total of 7,863
      consultations were requested by physicians over 1 year; 4,407 (56.0%) by
      ambulatory physicians, 2,933 (37.3%) by GUH physicians, and 523 (6.7%) by
      physicians in public or private hospitals. The majority of consultations were
      requested via cell phone (58.7%). The main reasons for requesting a consultation
      were related to antimicrobial treatment for hospital-based physicians and
      prophylaxis for ambulatory physicians (p < 0.001). Recommendations to perform
      diagnostic or monitoring tests were less frequent in ambulatory medicine (16%)
      than in the GUH (59%) or other hospitals (63%, p < 0.001). The route of
      consultation for patients with nosocomial infections was more likely to be formal
      (p < 0.001). The activity of the IDC hotline attests to an important need for
      such expertise consultation, both in hospitals and in ambulatory medicine.

PMID- 21069406
TI  - What to do and what not to do in serological diagnosis of pertussis:
      recommendations from EU reference laboratories.
AB  - Bordetella pertussis-specific antibodies can be detected by enzyme-linked
      immunosorbent assays (ELISAs) or multiplex immunoassays. Assays use purified or
      mixed antigens, and only pertussis toxin (PT) is specific for B. pertussis. The
      interpretation of results can be based on dual-sample or single-sample serology
      using one or two cut-offs. The EU Pertstrain group recommends that: (i) ELISAs
      and multiplex immunoassays should use purified non-detoxified PT as an antigen,
      that they should have a broad linear range and that they should express results
      quantitatively in International Units per millilitre (IU/ml); (ii) a single or
      dual diagnostic cut-off for single-serum serology using IgG-anti-PT between 50
      and 120 IU/ml should be used, and diagnostic serology cannot be validly
      interpreted for one year after vaccination with acellular pertussis (aP)
      vaccines; (iii) IgA-anti-PT should only be used with indeterminate IgG-anti-PT
      levels or when a second sample cannot be obtained. This group discourages using:
      (i) other antigens in routine diagnostics, as they are not specific; (ii) micro
      agglutination, due to its lack of sensitivity; (iii) immunoblots for pertussis
      serodiagnosis, as results cannot be quantified; (iv) other methods, such as
      complement fixation or indirect immunofluorescence, due to their low sensitivity
      and/or specificity.

PMID- 21069407
TI  - Scanning electron microscopy study of cavity preparation in deciduous teeth using
      the Er:YAG laser with different powers.
AB  - Using scanning electron microscopy (SEM) we evaluated the morphology of cavity
      surfaces in deciduous teeth prepared in vitro with the Er:YAG laser with
      different power parameters. Eight extracted cavity-free deciduous teeth with an
      intact crown were prepared using a traditional handpiece or an Er:YAG laser with
      different parameters (10 Hz/200 mJ, 10 Hz/300 mJ and 10 Hz/400 mJ). Samples were
      then processed and cavity surface morphology was evaluated by SEM to detect open
      dentinal tubules, or melting or cracking of the dentin. SEM showed that laser
      cavity preparation in deciduous teeth using different parameters left no smear
      layer and the dentinal tubules were clear. Dentin melting was not seen after
      cavity preparation at 200 mJ or 300 mJ, while visible dentin melting and cracks
      were detected at 400 mJ. The use of the laser at 10 Hz/200 mJ and 10 Hz/300 mJ
      for cavity preparation in deciduous teeth is safe and effective, but higher
      powers may damage the dentin.

PMID- 21069408
TI  - Susceptibility of Candida albicans, Staphylococcus aureus, and Streptococcus
      mutans biofilms to photodynamic inactivation: an in vitro study.
AB  - The purpose of this study was to evaluate specific effects of photodynamic
      inactivation (PDI) using methylene blue as photosensitizer and low-power laser
      irradiation on the viability of single-, dual-, and three-species biofilms formed
      by C. albicans, S. aureus, and S. mutans. Biofilms were grown in acrylic discs
      immersed in sterile brain heart infusion broth (BHI) containing 5% sucrose,
      inoculated with microbial suspension (10(6) cells/ml) and incubated for 5 days.
      On the fifth day, the effects of the methylene blue (MB) photosensitizer at a
      concentration of 0.1 mg/ml for 5 min and InGaAlP laser (660 nm) for 98 s, alone
      and conjugated were evaluated. Next, the discs were placed in tubes with sterile
      physiological solution [0.9% sodium chloride (NaCl)] and sonicated for to
      disperse the biofilms. Ten-fold serial dilutions were carried and aliquots seeded
      in selective agar, which were then incubated for 48 h. Then the numbers CFU/ml
      (log(10)) were counted and analyzed statistically (ANOVA, Tukey test, p < 0.05).
      Scanning electron microscopy (SEM) on discs treated with PDI and control biofilms
      groups was performed. Significant decreases in the viability of all
      microorganisms were observed for biofilms exposed to PDI mediated by MB dye.
      Reductions (log(10)) of single-species biofilms were greater (2.32-3.29) than the
      association of biofilms (1.00-2.44). Scanning electron microscopy micrographs
      suggested that lethal photosensitization occurred predominantly in the outermost
      layers of the biofilms. The results showed that PDI mediated by MB dye, might be
      a useful approach for the control of oral biofilms.

PMID- 21069409
TI  - Resistive index predicts renal prognosis in chronic kidney disease: results of a
      4-year follow-up.
AB  - BACKGROUND: While the clinical validity of Doppler ultrasonography in chronic
      kidney disease (CKD) is still controversial, we have shown in a 2-year follow-up
      study that the resistive index (RI) could estimate renal prognosis in CKD. The
      purpose of the present study is to determine whether RI could predict long-term
      renal prognosis in CKD. METHODS: We performed a 4-year follow-up study with an
      observational cohort of 281 CKD patients (GFR 51 +/- 31 ml/min/1.73 m(2), age 54
      +/- 17 years). The patients were examined by Doppler ultrasonography for RI
      [(peak-systolic velocity--end-diastolic velocity)/peak-systolic velocity] to be
      calculated. Glomerular filtration rate (GFR) was estimated with the revised
      Japanese equation. Worsening renal function was defined as a decrease in GFR of
      at least 20 ml/min/1.73 m(2) or the need for long-term dialysis therapy until the
      end of the 4-year follow-up. RESULTS: Among the 281 CKD patients, 89 patients
      presented with worsening renal function during the 4-year follow-up. When we
      divided the patients into two groups by RI value of 0.70, Kaplan-Meier analysis
      showed that the event-free rates of worsening renal function at 48 months were
      0.86 and 0.37 in patients with RI <= 0.70 and RI > 0.70, respectively (log-rank
      test, p < 0.001). Cox proportional-hazard analysis identified overt proteinuria
      (>= 1.0 g/g creatinine), high RI (>0.70), low GFR (<50 ml/min/1.73 m(2)) and high
      systolic blood pressure (>= 140 mmHg) as independent predictors of worsening
      renal function. CONCLUSIONS: This study demonstrated that high RI as well as
      proteinuria, low GFR, and hypertension were independent risk factors for the
      progression of CKD in the 4-year follow-up.

PMID- 21069410
TI  - The effects of raloxifene on bone turnover markers and bone mineral density in
      women on maintenance hemodialysis.
AB  - BACKGROUND: Bone disease is caused not only by increased bone turnover
      accompanying secondary hyperparathyroidism but also by factors such as bone
      metabolic disorder accompanying kidney disease and postmenopausal or age-related
      osteoporosis in hemodialysis patients. In this study, we investigated the effects
      of raloxifene on bone turnover markers and bone mineral density (BMD) in female
      hemodialysis patients to determine involvement of estrogen deficiency in bone
      disease. METHODS: The subjects were 47 female patients on maintenance
      hemodialysis. Raloxifene hydrochloride (60 mg) was administered to 21 patients
      for 1 year, and these patients were compared with a control group of 26 patients.
      Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx),
      bone alkaline phosphatase, and intact parathyroid hormone were measured, and BMD
      was determined by quantitative heel ultrasound as the speed of sound (SOS) in the
      calcaneus over this period. RESULTS: NTx decreased after treatment with
      raloxifene for 1 year, but significantly increased in the control group. SOS
      increased after treatment with raloxifene for 1 year, but significantly decreased
      in the control group. Treatment with raloxifene resulted in a significant
      decrease of NTx and a significant increase of SOS in subgroups of patients aged
      <60 and >= 60 years. CONCLUSIONS: Treatment with raloxifene can suppress a rise
      in NTx and increase bone mineral density in patients around the time of menopause
      and in postmenopausal patients of advanced age. A reduction in bone mineral
      density caused by estrogen deficiency may be involved in the development of bone
      disease in female hemodialysis patients.

PMID- 21069411
TI  - Atheroembolic renal disease with rapid progression and fatal outcome.
AB  - Atheroembolic renal disease is caused by foreign-body reaction to cholesterol
      crystals flushed from the atherosclerotic plaques into the small-vessel system of
      the kidneys. It is an underdiagnosed entity, mostly related to vascular
      procedures and/or anticoagulation, and prognosis is considered to be poor.
      Besides the benefit of aggressive medical prevention of further embolic events,
      use of steroid therapy has been associated with greater survival. Here we report
      a case of a patient with a multisystemic presentation of the disease days after
      performance of percutaneous coronary intervention and anticoagulation initiation
      due to an episode of myocardial infarction. Renal, cutaneous, ophthalmic,
      neurological, and possibly muscular and mesenteric involvement was diagnosed.
      Although medical treatment with corticosteroids and avoidance of further
      anticoagulation was applied, the patient rapidly progressed to end-stage renal
      disease requiring hemodialysis and died 6 months after diagnosis. This is a case
      of catastrophic progression of the disease resistant to therapeutic measures.
      Focus on diagnosis and more efficient preventive and therapeutic protocols are
      therefore needed.

PMID- 21069412
TI  - Effect of anemia on cardiac disorders in pre-dialysis patients immediately before
      starting hemodialysis.
AB  - INTRODUCTION: Anemia is a common complication of patients with chronic kidney
      disease (CKD), which not only lowers their quality of life but also potentially
      causes cardiovascular diseases such as congestive heart failure and coronary
      heart disease, and accelerates the progression of renal dysfunction. METHODS: Pre
      dialysis patients were assigned to groups A, B, C or D based on hemoglobin levels
      of <= 8.9 (n = 48), 9.0-9.9 (n = 63), 10-10.9 (n = 53), and >= 11.0 g/dL (n =
      39), respectively. Cardiac function was estimated using echocardiography to
      clarify the relationship between anemia and cardiac disorders in patients with
      CKD immediately before starting hemodialysis. RESULTS: Left ventricular ejection
      fraction (LVEF) was significantly higher in group D than in groups A and B. The
      fractions with an LVEF of less than 50% were 16.7, 4.8, 1.9, and 0% in groups A,
      B, C, and D, respectively. Posterior wall thickness was statistically thicker and
      the deceleration time of the early diastolic wave was longer in groups A and B,
      respectively, than in groups C and D. The left ventricular mass index in group D
      was significantly lower than in any other groups. CONCLUSION: Anemia in pre
      dialysis patients with CKD is a probable cause of impaired left ventricular
      systolic function and progressive left ventricular hypertrophy. Our results
      suggest that Hb levels should be maintained at >11 g/dL by EPO administration
      from the perspective of protecting cardiac function, although the upper limit of
      the target Hb level was undetermined.

PMID- 21069413
TI  - Meeting report: 2010 Caenorhabditis elegans Neurobiology Meeting, University of
      Wisconsin, USA.
AB  - Against the backdrop of the scenic Lake Mendota, the C. elegans Neurobiology
      Meeting came to a head. Expertly organised by Brian Ackley and Bruce Bamber and
      hosted at the accommodating University of Wisconsin, the meeting brought together
      recent contributions from many of the major research groups working on the
      neurobiology of C. elegans. With seven keynote speakers, 57 verbal presentations
      and hundreds of posters, this exciting event spanned a fascinating 3 days from 27
      June to 30 June 2010. In keeping with the tradition of this conference, the event
      on the whole was spearheaded by young investigators from several research
      institutions. The meeting served to emphasise the gains enjoyed by taking
      advantage of the genetic tractability of the worm. A thread that ran through the
      meeting was the importance of integrating data across different levels of
      biological organisation to permit delineation of the physiology underpinning
      discrete behavioural states. Recent advances in optogenetics and microfluidics
      were at the forefront of refining these analyses. The presentations discussed in
      this meeting report are a selection which reflects this overarching theme.

PMID- 21069414
TI  - Dynamic modeling for flow-activated chloride-selective membrane current in
      vascular endothelial cells.
AB  - In this paper, a dynamic model is proposed to quantify the relationship between
      fluid flow and Cl(-)-selective membrane current in vascular endothelial cells
      (VECs). It is assumed that the external shear stress would first induce channel
      deformation in VECs. This deformation could activate the Cl(-) channels on the
      membrane, thus allowing Cl(-) transport across the membrane. A modified Hodgkin
      Huxley model is embedded into our dynamic system to describe the
      electrophysiological properties of the membrane, such as the Cl(-)-selective
      membrane current (I), voltage (V) and conductance. Three flow patterns, i. e.,
      steady flow, oscillatory flow, and pulsatile flow, are applied in our simulation
      studies. When the extracellular Cl(-) concentration is constant, the I-V
      characteristics predicted by our dynamic model shows strong consistency with the
      experimental observations. It is also interesting to note that the Cl(-) currents
      under different flow patterns show some differences, indicating that VECs
      distinguish among and respond differently to different types of flows. When the
      extracellular Cl(-) concentration keeps constant or varies slowly with time (i.e.
      oscillates at 0.02 Hz), the convection and diffusion of Cl(-) in extracellular
      space can be ignored and the Cl(-) current is well captured by the modified
      Hodgkin-Huxley model alone. However, when the extracellular Cl(-) varies fast
      (i.e., oscillates at 0.2 Hz), the convection and diffusion effect should be
      considered because the Cl(-) current dynamics is different from the case where
      the convection-diffusion effect is simply ignored. The proposed dynamic model
      along with the simulation results could not only provide more insights into the
      flow-regulated electrophysiological behavior of the cell membrane but also help
      to reveal new findings in the electrophysiological experimental investigations of
      VECs in response to dynamic flow and biochemical stimuli.

PMID- 21069415
TI  - Elastic characterization of the gerbil pars flaccida from in situ inflation
      experiments.
AB  - In hearing science, finite element modelling is used commonly to study the
      mechanical behaviour of the middle ear. Correct quantitative elasticity
      parameters are an important input in these models. However, up till now, no large
      deformation elastic characterization of the pars flaccida, a small part of the
      tympanic membrane, has been carried out. In this paper, an elastic
      characterization of the gerbil pars flaccida is presented. The gerbil is used
      frequently as animal model in middle ear mechanics research. Characterization was
      done via inverse analysis of in situ static pressure inflation experiments. As a
      first approach, the pars flaccida was modelled as a linear homogeneous isotropic
      elastic membrane, which resulted in an average Young's modulus of <E> = (41.0 +/-
      0.4) kPa. It was found that linear elastic modelling cannot describe inflation
      stagnation at high pressures. Therefore, in a second approach, the Veronda
      Westmann hyperelastic model was introduced. This was able to describe curve
      stagnation, the mean parameters that were found are <C1> = (3.1 +/- 0.4) kPa and
      <C2> = (2.5 +/- 0.2). Finally, in situ strain was considered in the finite
      element models which resulted in a better description of the behaviour for small
      pressures. Incorporating this, the optimal Veronda-Westmann parameters are
      <CepsilonR1> = (2.6 +/- 0.6) kPa, <CepsilonR2> = (1.4 +/- 0.2) kPa for a radial
      in situ strain of <epsilonR> = (12 +/- 2)%. In conclusion, this paper shows that
      a linear elastic material is not appropriate to describe pars flaccida's
      behaviour in the quasi-static pressure regime, that the currently used membrane
      stiffness estimates do not hold for large deformations and that incorporating an
      in situ strain in the models is necessary for a good description for small static
      pressures.

PMID- 21069416
TI  - A sclerostin-based theory for strain-induced bone formation.
AB  - Bone formation responds to mechanical loading, which is believed to be mediated
      by osteocytes. Previous theories assumed that loading stimulates osteocytes to
      secrete signals that stimulate bone formation. In computer simulations this
      'stimulatory' theory successfully produced load-aligned trabecular structures. In
      recent years, however, it was discovered that osteocytes inhibit bone formation
      via the protein sclerostin. To reconcile this with strain-induced bone formation,
      one must assume that sclerostin secretion decreases with mechanical loading. This
      leads to a new 'inhibitory' theory in which loading inhibits osteocytes from
      inhibiting bone formation. Here we used computer simulations to show that a
      sclerostin-based model is able to produce a load-aligned trabecular architecture.
      An important difference appeared when we compared the response of the stimulatory
      and inhibitory models to loss of osteocytes, and found that the inhibitory
      pathway prevents the loss of trabeculae that is seen with the stimulatory model.
      Further, we demonstrated with combined stimulatory/inhibitory models that the two
      pathways can work side-by-side to achieve a load-adapted bone architecture.

PMID- 21069417
TI  - A novel experimental procedure based on pure shear testing of dermatome-cut
      samples applied to porcine skin.
AB  - This paper communicates a novel and robust method for the mechanical testing of
      thin layers of soft biological tissues with particular application to porcine
      skin. The key features include the use of a surgical dermatome and the highly
      defined deformation kinematics achieved by pure shear testing. Thin specimens of
      accurate thickness were prepared using a dermatome and were subjected to
      different quasi-static and dynamic loading protocols. Although simple in its
      experimental realisation, pure shear testing provides a number of advantages over
      other classic uni- and biaxial testing procedures. The preparation of thin
      specimens of porcine dermis, the mechanical tests as well as first representative
      results are described and discussed in detail. The results indicate a pronounced
      anisotropy between the directions along and across the cleavage lines and a
      strain rate-dependent response.

PMID- 21069418
TI  - Lipopolysaccharide (LPS) of helicobacter modulates cellular DNA repair systems in
      intestinal cells.
AB  - The epithelium of the intestinal tract is exposed to a variety of genotoxic
      agents, both exogenous and endogenous, that can injure nuclear and mitochondrial
      DNA. DNA damage can be repaired by a series of DNA repair enzymes, while defects
      in this system will make these cells once more susceptible to malignant
      transformation or cell death. Recent studies suggest that intestinal bacteria may
      contribute to induce inflammation in individuals afflicted by inflammatory bowel
      disease (IBD), increasing the risk of developing colon cancer. Accumulating
      evidence suggests that Helicobacter organisms are linked to IBD as well as to
      gastric and colon cancer. Therefore, the focus of this study was to evaluate the
      effect of lipopolysaccharide (LPS) isolated from Helicobacter on modulating the
      DNA repair system. We used an in vitro model represented by two colon carcinoma
      cell lines, the DNA repair-proficient SW480 and the DNA repair-deficient LoVo,
      and transfected with a UVC-irradiated psV-beta-galactosidase plasmid. We observed
      that LPS, by upregulating the expression of inducible nitric oxide (NO), leads to
      an increased NO release, demonstrating that LPS is able to interfere with the DNA
      repair machinery of intestinal cells, thus increasing the risk of permanent
      genotoxic effects.

PMID- 21069419
TI  - Osteoclastogenesis and arthritis.
AB  - There is emerging interest for osteoclasts as key players in the erosive and
      inflammatory events leading to joint destruction in chronic arthritis. In fact,
      chronic inflammatory joint diseases such as psoriatic arthritis and rheumatoid
      arthritis are often characterized by destruction of juxta-articular bone and
      erosions due to the elevated activity of osteoclasts, which are involved in bone
      resorption. The main step in inflammatory bone erosion is an imbalance between
      bone resorption and bone formation: osteoclast formation is enhanced by
      proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-17 and is not
      balanced by increased activity of bone-forming osteoblasts. T-cells, stromal
      cells, and synoviocytes enhance osteoclast formation via expression of RANKL and,
      under pathologic conditions, of proinflammatory cytokines. In rheumatoid
      arthritis, accumulation of osteoclasts in synovial tissues and their activation
      associated with osteoclastogenic cytokines and chemokines at cartilage erosion
      sites suggest that they could be usefully selected as therapeutic target. In
      particular, in consideration of the primary role of RANKL and TNF-alpha in
      osteoclastogenesis, the control of the production of RANKL and the inhibition of
      TNF-alpha represent important strategies for reducing bone damage in this
      disease.

PMID- 21069420
TI  - High mobility group box 1 induces synoviocyte proliferation in rheumatoid
      arthritis by activating the signal transducer and activator transcription signal
      pathway.
AB  - Recently, it was discovered that high mobility group box chromosomal protein 1
      (HMGB1) acts as a potent pro-inflammatory cytokine that is released into the
      extracellular milieu. Signal transducer and activator of transcription (STAT)
      proteins play an important role in cytokine signaling. Some investigators have
      reported preferential activation of STAT1, and others have reported preferential
      activation of STAT3 in response to endogenous interleukin-6 (IL-6) in patients
      with rheumatoid arthritis. Here, we show that expression of the HMGB1 protein is
      increased in the articular tissues of collagen-induced arthritis (CIA) rats,
      especially in cytoplasm and extracellular, following synoviocyte proliferation
      and STAT1 activation. In vitro, recombined human HMGB1 induced RSC-364 cell
      proliferation, activated STAT1 phosphorylation, increased the expression of
      cyclin D1 and CDK4 protein, and decreased the expression of p21 protein. In
      summary, our study suggests that HMGB1 plays an important role of cytokine in the
      pathogenesis of RA, which possibly induces synovial cell proliferation by
      activating the STAT1 signal pathway.

PMID- 21069421
TI  - Biological implications of preformed mast cell mediators.
AB  - Mast cells store an impressive array of preformed compounds (mediators) in their
      secretory granules. When mast cells degranulate, these are released and have a
      profound impact on any condition in which mast cell degranulation occurs. The
      preformed mast cell mediators include well-known substances such as histamine,
      proteoglycans, proteases, and preformed cytokines, as well as several recently
      identified compounds. Mast cells have recently been implicated in a large number
      of novel pathological settings in addition to their well-established contribution
      to allergic reactions, and there is consequently a large current interest in the
      molecular mechanisms by which mast cells act in the context of a given condition.
      In many cases, preformed mast cell mediators have been shown to account for
      functions ascribed to mast cells, and these compounds are hence emerging as major
      players in numerous pathologies. In this review we summarize the current
      knowledge of preformed mast cell mediators.

PMID- 21069422
TI  - Cell-specific and hypoxia-dependent regulation of human HIF-3alpha: inhibition of
      the expression of HIF target genes in vascular cells.
AB  - Hypoxia-inducible factors (HIF) are transcription factors responding to reduced
      oxygen levels and are of utmost importance for regulation of a widespread of
      cellular processes, e.g., angiogenesis. In contrast to HIF-1alpha/HIF-2alpha, the
      relevance of HIF-3alpha for the regulation of the HIF pathway in human vascular
      cells is largely unknown. HIF-3alpha mRNA increases under hypoxia in endothelial
      and vascular smooth muscle cells. Analysis of HIF-3alpha isoforms revealed a cell
      type-specific pattern, but only one isoform, HIF-3alpha2, is hypoxia-inducible.
      Reporter gene assays of the appropriate promoter localized a 31-bp fragment,
      mediating this hypoxic regulation. The contribution of HIF-1/2 and NFkappaB to
      the HIF-3alpha induction was verified. Functional studies focused on
      overexpression of HIF-3alpha isoforms, which decrease the hypoxia-mediated
      expression of VEGFA and Enolase2. These data support the notion of a hypoxia
      induced inhibitory function of HIF-3alpha and demonstrate for the first time the
      existence of this negative regulation of HIF-signaling in vascular cells.

PMID- 21069423
TI  - Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown
      transgenic mice.
AB  - Transgenic mice with a small hairpin RNA construct interfering with the
      expression of transient receptor potential vanilloid 1 (TRPV1) were created by
      lentiviral transgenesis. TRPV1 expression level in transgenic mice was reduced to
      8% while the expression of ankyrin repeat domain 1 (TRPA1) was unchanged. Ear
      oedema induced by topical application of TRPV1 agonist capsaicin was completely
      absent in TRPV1 knockdown mice. Thermoregulatory behaviour in relation to
      environmental thermopreference (30 vs. 35 degrees C) was slightly impaired in
      male knockdown mice, but the reduction of TRPV1 function was not associated with
      enhanced hyperthermia. TRPV1 agonist resiniferatoxin induced hypothermia and tail
      vasodilatation was markedly inhibited in knockdown mice. In conclusion, shRNA
      mediated knock down of the TRPV1 receptor in mice induced robust inhibition of
      the responses to TRPV1 agonists without altering the expression, gating function
      or neurogenic oedema provoked by TRPA1 activation. Thermoregulatory behaviour in
      response to heat was inhibited, but enhanced hyperthermia was not observed.

PMID- 21069425
TI  - Using remote sensing to map the risk of human monkeypox virus in the Congo Basin.
AB  - Although the incidence of human monkeypox has greatly increased in Central Africa
      over the last decade, resources for surveillance remain extremely limited. We
      conducted a geospatial analysis using existing data to better inform future
      surveillance efforts. Using active surveillance data collected between 2005 and
      2007, we identified locations in Sankuru district, Democratic Republic of Congo
      (DRC) where there have been one or more cases of human monkeypox. To assess what
      taxa constitute the main reservoirs of monkeypox, we tested whether human cases
      were associated with (i) rope squirrels (Funisciurus sp.), which were implicated
      in monkeypox outbreaks elsewhere in the DRC in the 1980s, or (ii) terrestrial
      rodents in the genera Cricetomys and Graphiurus, which are believed to be
      monkeypox reservoirs in West Africa. Results suggest that the best predictors of
      human monkeypox cases are proximity to dense forests and associated habitat
      preferred by rope squirrels. The risk of contracting monkeypox is significantly
      greater near sites predicted to be habitable for squirrels (OR = 1.32; 95% CI
      1.08-1.63). We recommend that semi-deciduous rainforests with oil-palm, the rope
      squirrel's main food source, be prioritized for monitoring.

PMID- 21069426
TI  - Differential diagnosis by unenhanced FLAIR T2-weighted magnetic resonance images
      between solitary high grade gliomas and cerebral metastases appearing as contrast
      enhancing cortico-subcortical lesions.
AB  - The aim was to assess the value of unenhanced fluid-attenuated inversion recovery
      T2-weighted sequences (FLAIR-T2) in the differential diagnosis between solitary
      high-grade gliomas (HGG) and cerebral metastases (CM) appearing as contrast
      enhancing cortico-subcortical lesions of the brain. In 69 patients with a
      contrast-enhancing cortico-subcortical brain lesion (43 HGG, and 26 CM),
      unenhanced FLAIR-T2 and gadolinium-enhanced FLAIR T1-weighted (Gd-FLAIR-T1) axial
      images have been reviewed for the involvement of the cortex adjacent to the
      contrast-enhancing lesion. In 27 (62.79%) out of 43 HGG, and 3 (11.53%) out of 26
      CM, the cortex adjacent to the contrast-enhancing lesion showed high signal
      intensity on unenhanced FLAIR-T2 without enhancement at Gd-FLAIR-T1. Fischer's
      exact probability test was P = 0.0003 when applied to HGG versus CM categories,
      indicating a significant difference. The high signal intensity on unenhanced
      FLAIR-T2 without gadolinium-enhancement of the cortex adjacent to the enhancing
      lesion is more frequently associated with HGG than CM.

PMID- 21069424
TI  - The physiological roles of phosducin: from retinal function to stress-dependent
      hypertension.
AB  - In the time since its discovery, phosducin's functions have been intensively
      studied both in vivo and in vitro. Phosducin's most important biochemical feature
      in in vitro studies is its binding to heterotrimeric G protein betagamma
      subunits. Data on phosducin's in vivo relevance, however, have only recently been
      published but expand the range of biological actions, as shown both in animal
      models as well as in human studies. This review gives an overview of different
      aspects of phosducin biology ranging from structure, phylogeny of phosducin
      family members, posttranscriptional modification, biochemical features,
      localization and levels of expression to its physiological functions. Special
      emphasis will be placed on phosducin's function in the regulation of blood
      pressure. In the second part of this article, findings concerning cardiovascular
      regulation and their clinical relevance will be discussed on the basis of
      recently published data from gene-targeted mouse models and human genetic
      studies.

PMID- 21069427
TI  - Recurrence in childhood medulloblastoma.
AB  - Thirty-eight consecutive children treated according to the HIT2000 and HIT91
      studies for medulloblastoma who suffered 40 recurrence events were identified
      from a neuroradiological database. Relapse was associated with younger median age
      compared with all children treated on HIT2000. Eight patients relapsed with
      isolated local recurrence. There was no correlation with incomplete surgical
      removal or violation of the respective treatment protocol. Four patients were
      younger than 4 years at time of initial presentation and thus were not treated
      primarily with radiotherapy, suggesting that delayed radiotherapy might be a
      contributing factor. Meningeal dissemination was present in 32 events; 16 were
      located in the frontal region, 8 of which were isolated nodular frontal and
      frontobasal meningeal disease. Circumscribed meningeal recurrences were
      associated with better overall survival (OS) compared with diffuse, widespread
      recurrences. Isolated frontobasal meningeal relapses are a well-known phenomenon
      in medulloblastomas even years after treatment and have been correlated to an
      underdose of radiation in many literature reports. However, in our patients there
      was no correlation to possible treatment violations, indicating that inadequate
      radiation dose to the frontobasal region was unlikely to be a causative factor.
      Surgical technique varied due to the multicentric nature of our study, so
      position during surgery was not recognized as a predisposing factor for
      frontobasal recurrence.

PMID- 21069428
TI  - Prognostic significance of cyclin A and B1 in pediatric embryonal tumors.
AB  - Embryonal tumors constitute the most common malignant brain tumor group in
      children. Although patient prognosis has been substantially improved over recent
      decades, identification of prognostic markers would be of obvious significance.
      In the present study we evaluated the prognostic significance of cyclin A and B1
      in correlation with Ki-67 index in pediatric embryonal tumors. We retrospectively
      evaluated 53 children with embryonic tumors who were treated surgically in our
      institute. All patients had regular follow-up examinations. The streptavidin
      biotin-horseradish peroxidase (HRP) method was performed on paraffin sections for
      detection of Ki-67/MIB-1, and cyclin A and B1. There were 42 cases of
      medulloblastoma (MB), 9 cases of atypical teratoid/rhabdoid tumor (AT/RT), and 2
      cases of supratentorial primitive neuroectodermal tumor (PNET). In MB patients,
      Ki-67 index >50% was associated with worse survival (P = 0.003). Cyclin A index
      >40% was associated with significantly poorer survival (P = 0.023). Patients with
      cyclin B1 index >15% exhibited a trend towards poorer survival (P = 0.068). On
      multivariate analysis, only Ki-67 index was identified as a factor with
      independent prognostic power. In AT/RT and PNET, there was high expression of Ki
      67 and variable expression of cyclin A and B1. Apart from Ki-67 index, cyclin A
      may have a prognostic role. Study of the above indices at diagnosis could alter
      or intensify treatment methods, so as to improve disease outcome. There is
      obviously a need for future studies with larger number of patients to confirm our
      preliminary observations.

PMID- 21069429
TI  - Ischemic colitis after capecitabine plus cisplatin treatment in advanced gastric
      cancer.
AB  - Systemic chemotherapy can be complicated by colonic toxicity, which usually
      determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis
      in patients with cancer. This report describes the case of a 45-year-old man with
      advanced gastric cancer who developed severe ischemic colitis after chemotherapy
      with cisplatin and capecitabine. The patient developed symptoms of
      gastrointestinal toxicity with abdominal pain and bloody diarrhea. He had a
      normal white blood cell count throughout his illness; the assay of stool
      specimens for Clostridium difficile toxins and the stool cultures were both
      negative. An endoscopy showed a mild, transient ischemic colitis. Although
      cisplatin is related to severe colonic cytotoxicity, it has not been previously
      reported that capecitabine induces arterial thrombosis and necrosis of the
      gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is
      the most frequent complication in patients with cancer who undergo capecitabine
      based chemotherapy and develop gastrointestinal toxicity. Once Clostridium
      difficile infection has been excluded, a diagnosis of ischemic colitis should be
      considered, especially in patients with cancer who have normal white blood cell
      counts.

PMID- 21069430
TI  - Functional characterization of four APETALA2-family genes (RAP2.6, RAP2.6L,
      DREB19 and DREB26) in Arabidopsis.
AB  - APETALA2 (AP2) transcription factors (TFs) play very important roles in plant
      growth and development and in defense response. Here, we report functional
      characterization of four AP2 TF family genes [(RAP2.6 (At1g43160), RAP2.6L
      (At5g13330), DREB 26 (At1g21910) and DREB19 (At2g38340)] that were identified
      among NaCl inducible transcripts in abscisic acid responsive 17 (ABR17)
      transgenic Arabidopsis in our previous microarray analyses. DREB19 and DREB26
      function as transactivators and localize in the nucleus. All four genes were
      abundant in early vegetative and flowering stages, although the magnitude of the
      expression varied. We observed tissue specific expression patterns for RAP2.6,
      RAP2.6L, DREB19 and DREB26 in flowers and other organs. RAP2.6 and RAP2.6L were
      responsive to stress hormones like jasmonic acid, salicylic acid, abscisic acid
      and ethylene in addition to salt and drought. DREB19 and DREB26 were less
      responsive to stress hormones, but the former was highly responsive to salt, heat
      and drought. Overexpression of RAP2.6 in Arabidopsis resulted in a dwarf
      phenotype with extensive secondary branching and small siliques, and DREB26
      overexpression resulted in deformed plants. However, overexpression of RAP2.6L
      and DREB19 enhanced performance under salt and drought stresses without affecting
      phenotype. In summary, we have demonstrated that RAP2.6, RAP2.6L, DREB26 and
      DREB19 are transactivators, they exhibit tissue specific expression, and they
      participate in plant developmental processes as well as biotic and/or abiotic
      stress signaling. It is possible that the results from this study on these
      transcription factors, in particular RAP2.6L and DREB19, can be utilized in
      developing salt and drought tolerant plants in the future.

PMID- 21069431
TI  - Effect of arsenic species on the growth and arsenic accumulation in Cucumis
      sativus.
AB  - The effects of arsenic (As) species, such as As(III), As(V) and dimethylarsinic
      acid (DMA), on the accumulation of As in cucumber (Cucumis sativus), as well as
      on its growth in a soil mesocosm were evaluated. When Cucumis sativus was
      cultivated in soils contaminated with 20 and 50 mg/kg of As(III), As(V) or DMA
      for 40 days, the growth was markedly inhibited by the inorganic As (As(III) and
      As(V)) rather than the organic As (DMA). Irrespective of the As species, the As
      concentrations accumulated in Cucumis sativus increased with increasing As
      concentration in the soil. The As bioaccumulation factors from soil into the
      tissue of Cucumis sativus were 17.5-35.4, 29.3-42.7 and 17.6-25.7 for As(III),
      As(V) and DMA, respectively. In addition, the As translocation factors from the
      roots to shoots were 0.025-0.031, 0.018-0.032 and 0.014-0.026 for As(III), As(V)
      and DMA, respectively. In conclusion, Cucumis sativus mainly accumulated As in
      its roots rather than its shoots and easily accumulated inorganic rather than
      organic As from the soil into its tissue.

PMID- 21069432
TI  - The beta-subunit of ATP synthase is involved in cellular uptake and resecretion
      of apoA-I but does not control apoA-I-induced lipid efflux in adipocytes.
AB  - Cellular uptake and resecretion of apoA-I (apoA-I recycling) could be an
      important factor in determining the circulating plasma levels of apoA-I and/or
      HDL. Using a novel method to study protein recycling, we have recently
      demonstrated recycling of apoA-I by adipocytes and suggested that this is a
      receptor mediated process independent of ABCA1 function. In the present study, it
      is shown that apoA-I recycling by adipocytes can be blocked by a monoclonal
      antibody against the beta-subunit of ATP synthase, a protein that had been
      previously identified as an apoA-I receptor. Investigation of the cellular
      recycling of two other proteins, an apolipoprotein and a small globular protein,
      showed that recycling of apoA-I is a selective process. The present study also
      shows that blocking apoA-I recycling has no effect on the rate of apoA-I-induced
      cholesterol or phospholipid efflux. It is concluded that cellular recycling of
      apoA-I is a selective process that involves the ectopically expressed beta
      subunit of ATP synthase. The physiological function of apoA-I recycling remains
      to be elucidated. However, this study shows that the process of apoA-I uptake and
      resecretion is not required for apoA-I lipidation.

PMID- 21069433
TI  - beta-Actin is a downstream effector of the PI3K/AKT signaling pathway in myeloma
      cells.
AB  - Interleukin 6 is the in vivo growth factor of myeloma cells. In response to IL-6
      stimulation, the PI3K/AKT signaling pathway is activated in these cells. With
      comparative proteomic approaches, this study reveals many putative downstream
      effectors of the PI3K/AKT pathway. Mass spectrometry analysis of excised protein
      spots from 2-dimensional gel allowed the identification of proteins such as beta
      Actin, cyclophilin A, E3 SUMO-protein ligase PIAS-NY protein, HSP 27, PML, and
      transforming growth factor beta-2. Among these putative effectors, beta-Actin was
      chosen for further characterization. Phosphorylation of beta-Actin by AKT upon IL
      6 stimulation was confirmed by western blotting using a phospho-AKT substrate
      antibody. Interestingly, IL-6 significantly increased cell migration (P < 0.05)
      and the content of filamentous actin (P < 0.05). Therefore, IL-6 stimulation
      could have effects on the migration of myeloma cells, and the phosphorylation of
      beta-Actin is probably involved in the process.

PMID- 21069434
TI  - Crosstalk between autophagy and apoptosis in the regulation of paclitaxel-induced
      cell death in v-Ha-ras-transformed fibroblasts.
AB  - The previous studies by this author group has shown that paclitaxel, a mitotic
      inhibitor used in breast cancer chemotherapy, inhibits cell growth via induction
      of Raf-1-dependent apoptosis. In this article, the role of autophagy in
      paclitaxel anticancer action was investigated using v-Ha-ras-transformed NIH 3T3
      cells. Paclitaxel induced a notable increase in the number of fluorescent
      particles labeled with monodansylcadaverine (MDC), a specific marker for
      autophagic vacuoles. MDC-labeled vacuoles clearly exhibited the fluorescent
      tagged LC3 in cells transiently overexpressing GFP-LC3 (a protein that associates
      with autophagosome membranes). However, autophagy inhibition with 3-methyladenine
      (3-MA) failed to rescue v-Ha-ras-transformed NIH 3T3 cells from paclitaxel
      induced cell death. More interestingly, the apoptosis inhibition by
      overexpression of the X-linked inhibitor of apoptosis (XIAP) did not fully block
      the cell death by paclitaxel, implying that apoptosis inhibition might accelerate
      the autophagic components of the paclitaxel response. Conversely, Raf-1 shRNA
      expression protected against paclitaxel-induced cell death through the
      simultaneous inhibition of both autophagy and apoptosis. These results suggest
      that both autophagy and apoptosis act as cooperative partners to induce cell
      death in v-Ha-ras-transformed NIH 3T3 cells treated with paclitaxel.

PMID- 21069435
TI  - Beneficial effect of insulin in hyperhomocysteinemia and diabetes mellitus
      induced vascular endothelium dysfunction: role of phosphoinositide dependent
      kinase and protein kinase B.
AB  - A primary defect in the vascular action of insulin may be the key intermediate
      mechanism that links endothelial dysfunction with diabetes mellitus and
      hyperhomocysteinemia. This study investigated the downstream targets of insulin,
      involved in this process. Hyperhomocysteinemia (serum homocysteine > 10 MUm/l)
      was produced in rats by administering L-methionine (1.7% w/w, p.o.x. 4 weeks) and
      diabetes mellitus (serum glucose > 140 mg/dl) was induced using streptozotocin
      (55 mg/kg/day, i.v. once) in another group. Four weeks after L-methionine and
      streptozotocin administration, vascular endothelium dysfunction was assessed in
      terms of attenuation of acetylcholine-induced, endothelium-dependent relaxation
      (isolated aortic ring preparation), decrease in serum nitrate/nitrite level, as
      well as mRNA expression of eNOS (rtPCR), and disruption of integrity of vascular
      endothelium. Both hyperhomocysteinemia and diabetes mellitus significantly
      attenuated acetylcholine-induced endothelial-dependent relaxation, and the
      increase in serum nitrite/nitrate concentration and the expression of eNOS.
      Insulin (0.4 and 0.6 IU/kg/day, s.c.) and atorvastatin (30 mg/kg/day, p.o.x. 4
      weeks) significantly improved all these parameters. However, this ameliorative
      effect of insulin was blocked by 7-hydroxystaurosporine (UCN-01) [Inhibitor of
      phosphoinositide dependent kinase (PDK)], and triciribine (API-2) (protein kinase
      B/Akt inhibitor). It is suggested that amelioration of vascular endothelium
      dysfunction by insulin may be due to stimulation of PDK and Akt pathways.

PMID- 21069436
TI  - Prevention of apoptosis by the interaction between FIH1 and Bax.
AB  - Bax induces mitochondrial-dependent cell apoptosis signals in mammalian cells.
      However, the mechanism of how Bax is kept inactive is not fully elucidated. Here,
      we identify FIH1 as a potential interactor of Bax through mass spectrometry
      analysis. Coimmunoprecipitation and GST pull-down experiments show that FIH1 can
      directly interact with Bax. Bax-mediated apoptosis is suppressed by FIH1
      overexpression, but accelerated by FIH1 deficiency. FIH1 functions as a cytosol
      retention factor of Bax, blocking Bax translocation from cytosol to mitochondria
      in response to apoptotic stimuli. Overall, there results unveil a novel role of
      FIH1 in the regulation of Bax-mediated apoptosis.

PMID- 21069437
TI  - Accessory food factors: understanding the catalytic function.
AB  - Despite the practical knowledge throughout the nineteenth century that citrus
      fruit cured scurvy, and that rickets and beriberi were diseases caused by poor
      diet, it was not until 1901 that animal feeding experiments led one investigator
      to propose the existence of 'accessory food factors,' a lack of which was
      determined to be the cause of some illnesses (Hopkins, 1949. In Joseph Needham
      and E. Baldwin (eds.), Hopkins and Biochemistry, 1861-1947: Papers Concerning Sir
      Frederick Gowland Hopkins, O.M., P.R.S., with a Selection of His Addresses and a
      Bibliography of His Publications. Cambridge: W. Heffer and Sons Ltd). The
      discovery of vitamins has long been considered as a delayed discovery. This delay
      has been attributed to the power of the germ theory in physiology at the time.
      While the germ theory and theories of auto-intoxication certainly played a role
      in delaying the discovery of vitamins, I argue further that it is important to
      consider the difference made to physiology by understanding the vitamins'
      catalytic function. The profound difference made to physiology by the vitamins'
      catalytic function suggests that a vitamin concept had previously been
      systematically inaccessible to researchers working within the conceptual
      framework of Bernardian physiology.

PMID- 21069438
TI  - High levels of microRNA-21 in the stroma of colorectal cancers predict short
      disease-free survival in stage II colon cancer patients.
AB  - Approximately 25% of all patients with stage II colorectal cancer will experience
      recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is
      upregulated in several cancer types and has been associated with survival in
      colon cancer. In the present study we developed a robust in situ hybridization
      assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically
      detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The
      expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon
      and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue
      chromogenic reaction, predominantly observed in fibroblast-like cells located in
      the stromal compartment of the tumors. The expression levels were measured using
      image analysis. The miR-21 signal was determined as the total blue area (TB), or
      the area fraction relative to the nuclear density (TBR) obtained using a red
      nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated
      significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI:
      1.06-1.55) in the stage II colon cancer patient group, whereas no significant
      correlation with disease-free survival was observed in the stage II rectal cancer
      group. In multivariate analysis both TB and TBR estimates were independent of
      other clinical parameters (age, gender, total leukocyte count, K-RAS mutational
      status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which
      when measured by image analysis identifies a subgroup of stage II colon cancer
      patients with short disease-free survival.

PMID- 21069439
TI  - Alarm pheromones do not mediate rapid shifts in honey bee guard acceptance
      threshold.
AB  - Honey bee (Apis mellifera) guards discriminate nestmates from non-nestmates at
      the hive entrance. The acceptance threshold of guards is known to change
      adaptively, for example becoming less permissive when the number of intruder bees
      from other colonies increases. These adaptive shifts can occur within minutes.
      What is unknown is the mechanism behind this rapid shift. It was hypothesized
      that alarm pheromones released by guards may cause the adoption of a less
      permissive acceptance threshold. Here, we tested this hypothesis on five
      discriminator hives by using a behavioral assay. We used three amounts each of
      iso-pentyl acetate (IPA) and 2-heptanone (2H), which are the major components of
      the pheromones from the sting and the mandibular glands, respectively.
      Biologically relevant levels of chemicals were delivered to the hive entrance
      platform via an air pump. We found no effect of either IPA or 2H: there was no
      change in guard acceptance of either nestmate (on average, 91% accepted) or non
      nestmate (on average, 30% accepted) under any of the pheromone treatments
      compared to the pentane control (98% nestmates accepted and 32% non-nestmates
      accepted). Therefore, we reject the hypothesis that the presence of IPA or 2H
      causes a rapid shift of guard acceptance threshold.

PMID- 21069440
TI  - Applying HFMEA to prevent chemotherapy errors.
AB  - To evaluate risk and vulnerability in the chemotherapy process using a proactive
      risk analysis method. Healthcare failure mode and effect analysis (HFMEA) was
      adopted to identify potential chemotherapy process failures. A multidisciplinary
      team is formed to identify, evaluate, and prioritize potential failure modes
      based on a chemotherapy process flowchart. Subsequently, a decision tree is used
      to locate potential failure modes requiring urgent improvement. Finally, some
      recommended actions are generated and executed to eliminate possible risks. A
      total of 11 failure modes were identified with high hazard scores in both
      inpatient and outpatient processes. Computerized physician order entry was
      adopted to eliminate potential risks in chemotherapy processes. Chemotherapy
      prescription errors significantly decreased from 3.34% to 0.40%. Chemotherapy is
      regarded as a high-risk process. Multiple errors can occur during ordering,
      preparing, compounding, dispensing, and administering medications. Subsequently,
      these can lead to serious consequences. HFMEA is a useful tool to evaluate
      potential risk in healthcare processes.

PMID- 21069441
TI  - Conformational transitions in Ariesaema curvatum lectin: characterization of an
      acid induced active molten globule.
AB  - Biophysical characterization of a lectin from Ariesaema curvatum (ACL) was
      carried out using steady state as well as time resolved fluorescence and CD
      spectroscopy under various denaturing conditions. An intermediate with altered
      tryptophan microenvironment was detected in the phase diagram, which exibited
      pronounced secondary structure and hemagglutinating activity in presence of 0.25
      M Gdn-HCl. An acid induced molten- globule like structure possessing activity and
      higher thermostability was detected. Transition to the molten globule state was
      reversible in nature. The lectin retained hemagglutinating activity even after
      incubation at 95  degrees C. Both chemical and thermal unfolding of the lectin
      were found to consist of multistate processes. Fluorescence quenching of ACL was
      strong with acrylamide and KI. The single tryptophan was found to be surrounded
      by high density of the positively charged amino acid residues as shown by a ten
      fold higher K(sv) for KI compared to that for CsCl. The average lifetime of
      tryptophan fluorescence increased from 1.24 ns in the native state to 1.72 ns in
      the denatured state.

PMID- 21069442
TI  - Mitochondrial dysfunction in neurological disorders with epileptic phenotypes.
AB  - A broad variety of mutations of the mitochondrial DNA or nuclear genes that lead
      to the impairment of mitochondrial respiratory chain or mitochondrial ATP
      synthesis have been associated with epileptic phenotypes. Additionally, evidence
      for an impaired mitochondrial function in seizure focus of patients with temporal
      lobe epilepsy and Ammon's horn sclerosis, as well as, animal models of temporal
      lobe epilepsy has been accumulated. This implies a direct pathogenic role of
      mitochondrial dysfunction in the process of epileptogenesis and seizure
      generation in certain forms of epilepsy.

PMID- 21069445
TI  - Intention perception in high functioning people with Autism Spectrum Disorders
      using animacy displays derived from human actions.
AB  - The perception of intent in Autism Spectrum Disorders (ASD) often relies on
      synthetic animacy displays. This study tests intention perception in ASD via
      animacy stimuli derived from human motion. Using a forced choice task, 28
      participants (14 ASDs; 14 age and verbal-I.Q. matched controls) categorized
      displays of Chasing, Fighting, Flirting, Following, Guarding and Playing, from
      two viewpoints (side, overhead) in both animacy and full video displays. Detailed
      analysis revealed no differences between populations in accuracy, or response
      patterns. Collapsing across groups revealed Following and Video displays to be
      most accurately perceived. The stimuli and intentions used are compared to those
      of previous studies, and the implication of our results on the understanding of
      Theory of Mind in ASD is discussed.

PMID- 21069444
TI  - The influence of L-carnitine suplementation on the antioxidative abilities of
      serum and the central nervous system of ethanol-induced rats.
AB  - The brain is exceptionally susceptible to oxidative stress that may be caused by
      xenobiotics such as ethanol. Alcohol metabolism is accompanied by enhanced free
      radical formation and a decrease in antioxidant abilities. However, L-carnitine
      appears to have antioxidant properties and the ability to regulate ethanol
      metabolism. The present study was designed to estimate the effect of L-carnitine
      on the antioxidant capacity of the rat brain and blood serum. For 5 weeks during
      the study, L-carnitine was given to rats in the amount of 1.5 g/1 l of drinking
      water, and from the second week the rats were intragastrically treated with
      ethanol. A significant decrease in the activity of antioxidant enzymes (Cu,Zn
      SOD, GSH-Px, GSSG-R and CAT) and in the level of non-enzymatic antioxidants
      (vitamin C, E, A, GSH and GSH-t) as well as a significant increase in the level
      of GSSG in the brain and blood serum of ethanol intoxicated rats have been
      demonstrated. It has also been shown that alcohol caused a significant increase
      in the level of lipid peroxidation products-lipid hydroperoxides, malondialdehyde
      and 4-hydroxynonenal-and an increase in dityrosine, as well as a decrease in
      tryptophan-markers of protein oxidative modifications. The administration of L
      carnitine to ethanol intoxicated rats partially normalized the activity of the
      examined enzymes and the level of the above non-enzymatic antioxidants. Moreover,
      L-carnitine significantly protects lipids and proteins against oxidative
      modifications. In conclusion, it has been proved that L-carnitine protects rat
      brain and blood serum against oxidative stress formation and it is possible that
      this small molecular amine has a similar beneficial effect on the human CNS.

PMID- 21069446
TI  - Population- and family-based studies associate the MTHFR gene with idiopathic
      autism in simplex families.
AB  - Two methylenetetrahydrofolate reductase gene (MTHFR) functional polymorphisms
      were studied in 205 North American simplex (SPX) and 307 multiplex (MPX) families
      having one or more children with an autism spectrum disorder. Case-control
      comparisons revealed a significantly higher frequency of the low-activity 677T
      allele, higher prevalence of the 677TT genotype and higher frequencies of the
      677T-1298A haplotype and double homozygous 677TT/1298AA genotype in affected
      individuals relative to controls. Family-based association testing demonstrated
      significant preferential transmission of the 677T and 1298A alleles and the 677T
      1298A haplotype to affected offspring. The results were not replicated in MPX
      families. The results associate the MTHFR gene with autism in SPX families only,
      suggesting that reduced MTHFR activity is a risk factor for autism in these
      families.

PMID- 21069448
TI  - Comprehensive cancer control: progress and accomplishments.
AB  - The potential for Comprehensive Cancer Control (CCC) across the nation has been
      realized in the last decade with 69 Coalitions developing and implementing CCC
      plans. Many partners at all levels--national, state, jurisdictional, tribal and
      communities--have contributed to this success. This article details the
      contribution of these partners across these various levels, with a selection of
      the many activities contributing to this success. Consequently the cancer burden,
      although still of major importance, continues to be addressed in significant
      ways. Although there are future challenges, CCC coalitions continue to play an
      important role in addressing the cancer burden.

PMID- 21069447
TI  - Dietary glycemic index, glycemic load, insulin index, fiber and whole-grain
      intake in relation to risk of prostate cancer.
AB  - OBJECTIVE: Insulin may play a role in prostate cancer tumorigenesis. Postprandial
      blood glucose and insulin responses of foods depend importantly on the
      carbohydrate quality and quantity, represented by glycemic index (GI), glycemic
      load (GL), fiber and whole-grain content, but are also influenced by intake of
      protein and other characteristics. The recently developed insulin index (II)
      quantifies the postprandial insulin secretion, also taking into account these
      additional characteristics. METHODS: We investigated the association between
      dietary GI, GL, II, fiber, and whole grains and risk of total prostate cancer (n
      = 5,112) and subgroups of prostate cancer as defined by stage or grade in 49,934
      male participants of the Health Professionals Follow-up Study. Multivariate
      adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated
      using Cox proportional hazards regression. RESULTS: Dietary GI, GL, II, or fiber
      was not associated with risk of total or subgroups of prostate cancer. We
      observed a positive association between dietary intake of whole grains and total
      prostate cancer (HR highest versus lowest quintile 1.13, 95% CI 1.03-1.24), which
      was attenuated after restriction to PSA-screened participants (HR 1.03, 95% CI
      0.91-1.17). CONCLUSIONS: These results suggest that long-term exposure to a diet
      with a high insulin response does not affect prostate cancer incidence.

PMID- 21069449
TI  - Plasma total nitric oxide and endothelial constitutive nitric oxide synthase
      (ecNOS) gene polymorphism: a study in a South Indian population.
AB  - In an analysis of the possible association of endothelial constitutive nitric
      oxide synthase (ecNOS) gene polymorphism and plasma nitric oxide levels in
      patients with acute coronary syndrome, we investigated 106 patients with the
      syndrome and 100 healthy controls. Genotype was determined using the polymerase
      chain reaction; plasma nitric oxide levels were found using ELISA. The genotype
      frequencies for the a/b polymorphism in the control group were 77% for bb, 19%
      for ab, and 4% for aa. In the patients, genotype frequencies were 55% bb, 34% ab,
      and 11% aa. The allele frequencies were 28% a and 72% b among the patients and
      13% a and 87% b among control subjects. Our findings showed a significant
      association of the ecNOS gene polymorphism with acute coronary syndrome in the
      South Indian population.

PMID- 21069450
TI  - Circulating levels of inflammatory markers and mammographic density among
      postmenopausal women.
AB  - Mammographic density is strongly associated with breast cancer risk. Inflammation
      is involved in breast carcinogenesis, perhaps through effects on mammographic
      density. We evaluated associations between inflammatory markers interleukin-6 (IL
      6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) and
      mammographic density among postmenopausal women. Plasma IL-6, TNF-alpha, and CRP
      levels were measured in 145 women with benign breast disease (benign controls)
      and 397 women with a negative screening mammogram (well controls) enrolled in the
      Mammograms and Masses Study. Associations between the inflammatory markers and
      mammographic density were evaluated separately for benign and well controls
      through correlation analyses and linear regressions. Age-adjusted mean CRP levels
      were higher among benign controls (2.07 MUg/ml) compared to well controls (1.63
      MUg/ml; P = 0.02), while IL-6 and TNF-alpha levels were similar between groups.
      Using linear regression, IL-6, TNF-alpha, and CRP were not statistically
      significantly associated with dense breast area within either group.
      Statistically significant positive associations were observed between all three
      markers and nondense breast area in both groups; statistically significant
      negative associations were observed between IL-6 and percent density among benign
      controls, and between all three markers and percent density among well controls.
      These associations were all attenuated and non-significant upon adjustment for
      body mass index. IL-6, TNF-alpha, and CRP levels were not independently
      associated with dense breast area, nondense breast area, or percent density in
      this study population. Our results suggest that these inflammatory factors do not
      impact breast carcinogenesis through independent effects on mammographic density.

PMID- 21069452
TI  - Nuclear co-localization and functional interaction of COX-2 and HIF-1alpha
      characterize bone metastasis of human breast carcinoma.
AB  - The aim of this article is to identify nuclear co-localization of COX-2 and HIF
      1alpha in human-bone metastasis of breast cancer, index of transcriptionally
      activated cells and functional for gene expression. In particular, we verified
      whether hypoxia exerted a direct role on metastasis-gene expression or through
      COX-2 signaling, due to the relevance for clinical implications to individuate
      molecular targets for diagnosis and therapy. The experiments were performed in
      vitro with two metastatic clones, 1833 and MDA-231BO, and the parental MDA-MB231
      cells, in vivo (1833-xenograft model), and in human-bone metastasis specimens. In
      1833 cells in vitro, COX-2 signaling pathway was critical for nuclear HIF-1alpha
      protein expression/translocation, mechanisms determining HIF-1 activity and gene
      expression. The data were corroborated by immunohistochemistry in human-bone
      metastasis specimens. COX-2 and HIF-1alpha showed wide co-localization in the
      nucleus, indicative of COX-2-nuclear import in transcriptionally activated
      metastatic cells and consistent with COX-2-HIF-1alpha functional interaction. A
      network of microenvironmental signals controlled COX-2 induction and HIF-1
      activation downstream. In fact, hypoxia through HGF and TGF-beta1 autoregulatory
      loops triggered a specific array of transcription factors responsible for COX-2
      transactivation. The novelty was that HGF and TGF-beta1 biological signals were
      produced by hypoxic metastatic cells and, therefore, the microenvironment seemed
      to be modified by metastatic-cell engraftment in the bone. In agreement, HIF
      1alpha expression in bone marrow supportive cells occurred in metastasis-bearing
      animals. Altogether, the data supported the pre-metastatic-niche theory. Our
      observations might be useful to design therapies against bone metastasis, by
      affecting the phenotype changes of metastatic cells occurring at the secondary
      growth site through COX-2-HIF-1 interaction.

PMID- 21069451
TI  - Aberrant expression of DNA damage response proteins is associated with breast
      cancer subtype and clinical features.
AB  - Landmark studies of the status of DNA damage checkpoints and associated repair
      functions in preneoplastic and neoplastic cells has focused attention on
      importance of these pathways in cancer development, and inhibitors of repair
      pathways are in clinical trials for treatment of triple negative breast cancer.
      Cancer heterogeneity suggests that specific cancer subtypes will have distinct
      mechanisms of DNA damage survival, dependent on biological context. In this
      study, status of DNA damage response (DDR)-associated proteins was examined in
      breast cancer subtypes in association with clinical features; 479 breast cancers
      were examined for expression of DDR proteins gammaH2AX, BRCA1, pChk2, and p53,
      DNA damage-sensitive tumor suppressors Fhit and Wwox, and Wwox-interacting
      proteins Ap2alpha, Ap2gamma, ErbB4, and correlations among proteins, tumor
      subtypes, and clinical features were assessed. In a multivariable model, triple
      negative cancers showed significantly reduced Fhit and Wwox, increased p53 and
      Ap2gamma protein expression, and were significantly more likely than other
      subtype tumors to exhibit aberrant expression of two or more DDR-associated
      proteins. Disease-free survival was associated with subtype, Fhit and membrane
      ErbB4 expression level and aberrant expression of multiple DDR-associated
      proteins. These results suggest that definition of specific DNA repair and
      checkpoint defects in subgroups of triple negative cancer might identify new
      treatment targets. Expression of Wwox and its interactor, ErbB4, was highly
      significantly reduced in metastatic tissues vs. matched primary tissues,
      suggesting that Wwox signal pathway loss contributes to lymph node metastasis,
      perhaps by allowing survival of tumor cells that have detached from basement
      membranes, as proposed for the role of Wwox in ovarian cancer spread.

PMID- 21069454
TI  - Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta
      analysis.
AB  - Although poly(ADP-ribose) polymerase-1 (PARP1) inhibition is a recent promising
      therapy in breast cancer, PARP1 expression in this disease is not known. Using
      DNA microarray and array-based comparative genomic hybridization (arrayCGH), we
      examined PARP1 mRNA expression and copy number alterations in 326 invasive breast
      cancer samples and normal breast (NB) samples. A meta-analysis was performed on a
      large public retrospective gene expression data set (n = 2,485) to analyze
      correlation between PARP1 mRNA expression and molecular subtypes and clinico
      pathological parameters. PARP1 was overexpressed in 58% of cancers, and its
      expression was heterogeneous between tumors. ArrayCGH data revealed an
      association between mRNA overexpression and gain/amplification at the PARP1 locus
      (P < 1.0E-8). Meta-analysis showed that PARP1 expression was higher in basal
      breast cancers (P < 1.0E-72), but overexpression was also found in other
      subtypes. PARP1 expression correlated with high grade, medullary histological
      type, tumor size, and worse metastasis-free survival (MFS; HR = 1.12 [1.04-1.22],
      P = 0.004) and overall survival (OS; HR = 1.16 [1.04-1.29], P = 0.006). In
      multivariate analysis, PARP1 expression had an independent prognostic value for
      MFS, which was restricted to patients untreated with any adjuvant chemotherapy.
      These data demonstrate overexpression of PARP1 in a large number of breast
      cancers and support the development of PARP inhibitors in basal subtype, but also
      potentially in other breast cancer subtypes.

PMID- 21069455
TI  - Bark regeneration and tannin content in Myracrodruon urundeuva Allemao after
      simulation of extractive damages--implications to management.
AB  - Due to the current exploitation and consequent extinction of native medicinal
      plants around the world, new strategies have been proposed to address the
      sustainable use of this resource. Accordingly, the goal of this study is to
      assess the speed of bark regeneration of Myracrodruon urundeuva Allemao and to
      compare the tannin content before and after tissue regeneration. Twenty
      individuals from an area of Caatinga in Caruaru, Pernambuco State (NE Brazil),
      were selected. To evaluate the speed of bark regeneration, four treatments were
      established, according to the area of bark removed (10 * 2, 6 * 5, 8 * 5 and 10 *
      5 cm), with five replicates (five individuals of M. urundeuva Allemao) and three
      treatments of tannin content (bark removed before damage, as regenerated tissue,
      and non-impacted bark or control). At the end of 23 months of monitoring the
      regeneration, we found that only seven of the 20 individuals analyzed did not
      fully heal. No significant correlation between the monthly percent regeneration
      and average monthly precipitation was found. The tannin content varied according
      to the quantified tissue (after damage, regenerated and control) as well as
      between damage classes (20 cm(2)-41.64 to 63.53 mg; 30 cm(2)-49.25 to 67.54 mg;
      40 cm(2)-31.69 to 67.44 mg; 50 cm(2)-34.08 to 48.53 mg). Despite the variations
      found, there was no significant difference between the measurement periods (p >
      0.05) or damage classes (p > 0.05). The results showed that the regeneration rate
      was higher in individuals belonging to the 10 * 2 and 10 * 5 cm groups and that
      there is no correlation between precipitation and regeneration speed. Tannin
      levels did not vary significantly in the tissues before damage and after
      regeneration.

PMID- 21069453
TI  - Local anesthetics inhibit kinesin motility and microtentacle protrusions in human
      epithelial and breast tumor cells.
AB  - Detached breast tumor cells produce dynamic microtubule protrusions that promote
      reattachment of cells and are termed tubulin microtentacles (McTNs) due to their
      mechanistic distinctions from actin-based filopodia/invadopodia and tubulin-based
      cilia. McTNs are enriched with vimentin and detyrosinated alpha-tubulin, (Glu
      tubulin). Evidence suggests that vimentin and Glu-tubulin are cross-linked by
      kinesin motor proteins. Using known kinesin inhibitors, Lidocaine and Tetracaine,
      the roles of kinesins in McTN formation and function were tested. Live-cell McTN
      counts, adhesion assays, immunofluorescence, and video microscopy were performed
      to visualize inhibitor effects on McTNs. Viability and apoptosis assays were used
      to confirm the non-toxicity of the inhibitors. Treatments of human non
      tumorigenic mammary epithelial and breast tumor cells with Lidocaine or
      Tetracaine caused rapid collapse of vimentin filaments. Live-cell video
      microscopy demonstrated that Tetracaine reduces motility of intracellular GFP
      kinesin and causes centripetal collapse of McTNs. Treatment with Tetracaine
      inhibited the extension of McTNs and their ability to promote tumor cell
      aggregation and reattachment. Lidocaine showed similar effects but to a lesser
      degree. Our current data support a model in which the inhibition of kinesin motor
      proteins by Tetracaine leads to the reductions in McTNs, and provides a novel
      mechanism for the ability of this anesthetic to decrease metastatic progression.

PMID- 21069456
TI  - Variations in seasonal phytoplankton assemblages as a response to environmental
      changes in the surface waters of a hypo saline coastal station along the
      Bhagirathi-Hooghly estuary.
AB  - Due to the close proximity of the Bay of Bengal and the freshwater inflow of
      Bhagirathi-Hooghly, Diamond Harbour appeared as an important coastal station of
      the Bhagirathi-Hooghly estuary. The spatial and temporal composition and
      abundance of microphytoplankton species was examined in relation to physical and
      chemical surface water variables (i.e., salinity, nutrient, and temperature).The
      primary objective of the study was to observe the variations in phytoplankton
      species assemblages as a response to environmental variables. Hierarchical
      cluster analysis and non-metric multidimensional scaling were used to find out
      distinct seasonal groups based on the composition of phytoplankton. The results
      indicate that several key environmental factors like temperature, DIN content,
      and molar ratio of nutrients like DIN-DIP and DIN-DSi influenced seasonal
      phytoplankton assemblages within the estuary. The distribution of phytoplankton
      population showed two main groups where the blue-green and green algal
      populations favored the warmer conditions of summer and monsoon months, whereas
      the diatom population primarily flourished in the cooler months of autumn and
      winter.

PMID- 21069457
TI  - A decade of monitoring at Swiss Long-Term Forest Ecosystem Research (LWF) sites:
      can we observe trends in atmospheric acid deposition and in soil solution
      acidity?
AB  - Trends in atmospheric acid deposition and in soil solution acidity from 1995 or
      later until 2007 were investigated at several forest sites throughout Switzerland
      to assess the effects of air pollution abatements on deposition and the response
      of the soil solution chemistry. Deposition of the major elements was estimated
      from throughfall and bulk deposition measurements at nine sites of the Swiss Long
      Term Forest Ecosystem Research network (LWF) since 1995 or later. Soil solution
      was measured at seven plots at four soil depths since 1998 or later. Trends in
      the molar ratio of base cations to aluminum (BC/Al) in soil solutions and in
      concentrations and fluxes of inorganic N (NO(3)-N + NH(4)-N), sulfate (SO(4)-S),
      and base cations (BC) were used to detect changes in soil solution chemistry.
      Acid deposition significantly decreased at three out of the nine study sites due
      to a decrease in total N deposition. Total SO(4)-S deposition decreased at the
      nine sites, but due to the relatively low amount of SO(4)-S load compared to N
      deposition, it did not contribute to decrease acid deposition significantly. No
      trend in total BC deposition was detected. In the soil solution, no trend in
      concentrations and fluxes of BC, SO(4)-S, and inorganic N were found at most soil
      depths at five out of the seven sites. This suggests that the soil solution
      reacted very little to the changes in atmospheric deposition. A stronger
      reduction in base cations compared to aluminum was detected at two sites, which
      might indicate that acidification of the soil solution was proceeding faster at
      these sites.

PMID- 21069459
TI  - Influence of different ammonium, lactate and glutamine concentrations on CCO cell
      growth.
AB  - In this study the effects of ammonium and lactate on a culture of channel catfish
      ovary (CCO) cells were examined. We also made investigation on the influence of
      glutamine, since our previous research revealed that this amino acid stimulated
      CCO cell growth more than glucose in a concentration-dependent manner. The effect
      of ammonium in cell culture included the considerable decrease in cell growth
      rate with eventual growth arrest as well as the retardation of glucose
      consumption. At ammonium concentrations above 2.5 mM, the cells displayed
      specific morphological changes. The effect of lactate was different to that of
      ammonium since the cell growth rate was progressively decreasing with the
      increase of lactate concentration, whereas the glucose consumption rate remained
      almost unchanged. Besides that, it was found that lactate was steadily eliminated
      from the culture medium when its initial concentration was relatively high. The
      influence of glutamine on CCO cell propagation showed that nutrient requirements
      of this cell line were mainly dependent on glutamine rather than glucose. The
      increase in glutamine concentration led to the increase in cell growth rate and
      consequent ammonia accumulation while the glucose utilization and lactate
      production were reduced. Without glutamine in culture medium cell growth was
      arrested. However, the lack of glucose reversed the stimulating effect of
      glutamine by decreasing cell growth rate and affecting amino acid utilization.

PMID- 21069458
TI  - Multimodality imaging in the assessment of myocardial viability.
AB  - The prevalence of heart failure due to coronary artery disease continues to
      increase, and it portends a worse prognosis than non-ischemic cardiomyopathy.
      Revascularization improves prognosis in these high-risk patients who have
      evidence of viability; therefore, optimal assessment of myocardial viability
      remains essential. Multiple imaging modalities exist for differentiating viable
      myocardium from scar in territories with contractile dysfunction. Given the
      multiple modalities available, choosing the best modality for a specific patient
      can be a daunting task. In this review, the physiology of myocardial hibernation
      and stunning will be reviewed. All the current methods available for assessing
      viability including echocardiography, cardiac magnetic resonance imaging, nuclear
      imaging with single photon emission tomography and positron emission tomography
      imaging and cardiac computed tomography will be reviewed. The effectiveness of
      the various techniques will be compared, and the limitations of the current
      literature will be discussed.

PMID- 21069460
TI  - Accumulation of functional recombinant human coagulation factor IX in transgenic
      soybean seeds.
AB  - The seed-based production of recombinant proteins is an efficient strategy to
      achieve the accumulation, correct folding, and increased stability of these
      recombinant proteins. Among potential plant molecular farming systems, soybean
      [Glycine max (L.) Merrill] is a viable option for the production of recombinant
      proteins due to its high protein content, known regulatory sequences, efficient
      gene transfer protocols, and a scalable production system under greenhouse
      conditions. We report here the expression and stable accumulation of human
      coagulation factor IX (hFIX) in transgenic soybean seeds. A biolistic process was
      utilised to co-introduce a plasmid carrying the hFIX gene under the
      transcriptional control of the alpha' subunit of a beta-conglycinin seed-specific
      promoter and an alpha-Coixin signal peptide in soybean embryonic axes from mature
      seeds. The 56-kDa hFIX protein was expressed in the transgenic seeds at levels of
      up to 0.23% (0.8 g kg(-1) seed) of the total soluble seed protein as determined
      by an enzyme-linked immunosorbent assay (ELISA) and western blot. Ultrastructural
      immunocytochemistry assays indicated that the recombinant hFIX in seed
      cotyledonary cells was efficiently directed to protein storage vacuoles. Mass
      spectrometry characterisation confirmed the presence of the hFIX recombinant
      protein sequence. Protein extracts from transgenic seeds showed a blood-clotting
      activity of up to 1.4% of normal plasma. Our results demonstrate the correct
      processing and stable accumulation of functional hFIX in soybean seeds stored for
      6 years under room temperature conditions (22 +/- 2 degrees C).

PMID- 21069461
TI  - Expression of functional recombinant human growth hormone in transgenic soybean
      seeds.
AB  - We produced human growth hormone (hGH), a protein that stimulates growth and cell
      reproduction, in genetically engineered soybean [Glycine max (L.) Merrill] seeds.
      Utilising the alpha prime (alpha') subunit of beta-conglycinin tissue-specific
      promoter from soybean and the alpha-Coixin signal peptide from Coix lacryma-jobi,
      we obtained transgenic soybean lines that expressed the mature form of hGH in
      their seeds. Expression levels of bioactive hGH up to 2.9% of the total soluble
      seed protein content (corresponding to approximately 9 g kg(-1)) were measured in
      mature dry soybean seeds. The results of ultrastructural immunocytochemistry
      assays indicated that the recombinant hGH in seed cotyledonary cells was
      efficiently directed to protein storage vacuoles. Specific bioassays demonstrated
      that the hGH expressed in the soybean seeds was fully active. The recombinant hGH
      protein sequence was confirmed by mass spectrometry characterisation. These
      results demonstrate that the utilisation of tissue-specific regulatory sequences
      is an attractive and viable option for achieving high-yield production of
      recombinant proteins in stable transgenic soybean seeds.

PMID- 21069462
TI  - Homocysteine and vascular disease: review of published results of the
      homocysteine-lowering trials.
AB  - Moderately elevated homocysteine levels have been associated with a higher risk
      of cardiovascular disease in observational studies, but whether these
      associations are causal is uncertain. Randomized trials of dietary
      supplementation with B vitamins were set up to assess whether lowering
      homocysteine levels could reduce the risk of vascular disease. This review is
      based on a meta-analysis of published results of eight homocysteine-lowering
      trials for preventing vascular disease. The eight trials comprised a total of
      37,485 individuals and provided comparisons of the effects of B vitamins on 5,074
      coronary heart disease (CHD) events, 1,483 stroke events, 2,692 incident cancer
      events, and 5,128 deaths. Our meta-analysis assessed the effects of lowering
      homocysteine levels by about 25% for about 5 years. Allocation to B vitamins had
      no beneficial effects on any cardiovascular events, with hazard ratios (95%
      confidence intervals) of 1.01 (0.96-1.07) for CHD and 0.96 (0.87-1.07) for
      stroke. Moreover, allocation to B vitamins had no significant adverse effects on
      cancer [1.08 (0.99-1.17)], or for death from any cause [1.02 (0.97-1.07)]. Thus,
      supplementation with B vitamins had no statistically significant effects on the
      risks of cardiovascular events, total mortality rates, or cancer. A meta-analysis
      based on individual participant data from all available trials will assess the
      effects of lowering homocysteine levels on a broader range of outcomes, overall
      and in all relevant subgroups. However, available evidence does not support the
      routine use of B vitamins to prevent cardiovascular disease.

PMID- 21069463
TI  - Exacerbation of erythropoietic protoporphyria by hyperthyroidism.
AB  - Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by deficiency
      of ferrochelatase, the last enzyme in the heme biosynthetic pathway. The majority
      of EPP patients present with a clinical symptom of painful phototoxicity. Liver
      damage, the most serious complication of EPP, occurs in <5% of the patients. This
      report describes a case of an EPP patient who complained of worsening cutaneous
      symptoms, nervousness, and insomnia. Laboratory tests showed highly increased
      protoporphyrin concentration in erythrocytes and elevated serum transaminases
      that are indicative of EPP-related liver damage. The subsequent finding of
      decreased serum thyroid-stimulating hormone (TSH) and increased free
      triiodothyronine (FT3) and free thyroxine (FT4) concentrations, as well
      antibodies against both thyroid peroxidase (TPO) and TSH receptors, led to the
      diagnosis of Graves' disease. The patient received 500 MBq of radioiodine
      (I(131)). Three months after the radioactive iodine therapy, the thyroid volume
      was reduced to 30% of pretherapeutic volume. Although the patient was slightly
      hypothyroidic, his liver enzymes returned to normal, his erythrocytic
      protoporphyrin concentration dropped fivefold, and his skin symptoms improved
      dramatically. The coexistence of Graves' disease and EPP is a statistically rare
      event as, besides our patient, there was one additional case reported in the
      literature. Although the exact mechanism whereby Graves' disease interacts with
      EPP is yet to be explored, we recommend testing thyroid function in EPP patients
      with liver complication to exclude hyperthyroidism as a potential cause.

PMID- 21069464
TI  - Molecular cloning and expression analysis of a novel SANT/MYB gene from Gossypium
      barbadense.
AB  - MYB family transcription factors are implicated in multiple developmental
      processes. Herein, a new full-length cDNA encoding a SANT/MYB transcription
      factor (designated as GbRL2) was cloned and characterized from cotton (Gossypium
      barbadense L.) for the first time. The full-length cDNA of GbRL2 was 573 bp with
      a 240 bp open reading frame (ORF) encoding a deduced protein of 80 amino acid
      polypeptide with a calculated molecular mass of 8.96 kDa and an isoelectric point
      of 8.96. Sequence alignment revealed that GbRL2 had high homology with other
      single SANT/MYB domain containing genes, including the RADIALIS genes in
      Antirrhinum majus and Bournea leiophylla. Semi-quantitative reverse transcript
      polymerase chain reaction (RT-PCR) revealed that at seedling stage, GbRL2 was
      strongly expressed in leaves but merely in stems. In opening flowers, the
      expression of GbRL2 was moderate in the petals but could not be detected in
      stamens. In ovules, the expression of GbRL2 could not be detected at -3 days post
      anthesis (DPA) but increased during early elongation stage (0 DPA, +3 DPA, +5 DPA
      and +8 DPA). The transcripts of GbRL2 could also be detected at +8 DPA elongating
      fibers. We also examined the expression of RL2 gene in Gossypium hirstum cultivar
      Xu-142 and its fuzzless-lintless-seed mutant fl plants. The GhRL2 gene was
      ectopically expressed at -3 DPA in the fl mutant while the expression of GhRL2 in
      WT could not be detected. The expression of GhRL2 decreased early (+5 DPA) while
      that of WT was still strong. Our results suggest that GbRL2 may participate in
      development of various organs and may be a target for genetic improvement of
      cotton fiber.

PMID- 21069465
TI  - Ikaros expression in tongue sole macrophages: a marker for lipopolysaccharide-
      and lipoteichoic acid-induced inflammatory responses.
AB  - Ikaros, an important transcription factor plays a role in the development of
      hemato-lymphoid system, yet its functional importance in fish macrophages remains
      unknown. In this study, an Ikaros cDNA was cloned from the half-smooth tongue
      sole Cynoglossus semilaevis. The cDNA contained an open reading frame of 1,290
      nucleotides that encoded a 430 amino acid protein. The deduced protein is
      structurally similar to dul from other species, for example human, axolotl, and
      possesses 3-zinc finger and 2-zinc finger domains at its N- and C-termini,
      respectively. Phylogenetic analysis revealed C. semilaevis Ikaros to be grouped
      with all the fish Ikaros, but branching from other Ikaros family members. Both
      semi-quantitative PCR and quantitative real-time PCR indicated Ikaros to be
      predominantly expressed in the immune-relevant tissues such as kidney, thymus,
      spleen and liver. In the macrophages cultured from C. semilaevis head kidney and
      challenged with lipopolysaccharide and lipoteichoic acid not only induced
      expression of the proinflammatory cytokines tumor necrosis factor-alpha and
      interleukin 1-beta but also caused up-regulation of Ikaros in a dose- and time
      dependent fashions. All these data suggest that Ikaros might be a useful marker
      for inflammatory responses in C. semilaevis.

PMID- 21069467
TI  - Sequential transcatheter arterial chemoembolization and portal vein embolization
      versus portal vein embolization only before major hepatectomy for patients with
      hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the safety and efficacy of sequential transcatheter arterial
      chemoembolization (TACE) and portal vein embolization (PVE) prior to surgery in
      hepatocellular carcinoma (HCC) patients and to compare the clinical outcome of
      the combined procedure with that of a matched group of patients undergoing PVE
      alone. PATIENTS AND METHODS: From 1997 to 2008, 135 patients with HCC underwent
      sequential TACE and PVE (n = 71) or PVE alone (n = 64) before right hepatectomy.
      PVE was performed mean 1.2 months after TACE. In both groups, computed tomography
      (CT) and liver volumetry were performed before and 2 weeks after PVE to assess
      degree of left lobe hypertrophy. RESULTS: Baseline patient and tumor
      characteristics were similar in the two groups. After PVE, the chronological
      changes of liver enzymes were similar in the two groups. The mean increase in
      percentage future liver remnant (FLR) volume was higher in the TACE + PVE group
      (7.3%) than in the PVE-only group (5.8%) (P = 0.035). After surgery, incidence of
      hepatic failure was higher in the PVE-only group (12%) than in the TACE + PVE
      (4%) group (P = 0.185). Overall (P = 0.028) and recurrence-free (P = 0.001)
      survival rates were significantly higher in the TACE + PVE group than in the PVE
      only group. CONCLUSION: Sequential TACE and PVE before surgery is a safe and
      effective method to increase the rate of hypertrophy of the FLR and leads to
      longer overall and recurrence-free survival in patients with HCC.

PMID- 21069468
TI  - Ex vivo sentinel lymph nodes in pathological staging of node-negative colorectal
      carcinoma.

PMID- 21069466
TI  - Anatomic magnetic resonance imaging of the developing child and adolescent brain
      and effects of genetic variation.
AB  - Magnetic resonance imaging studies have begun to map effects of genetic variation
      on trajectories of brain development. Longitudinal studies of children and
      adolescents demonstrate a general pattern of childhood peaks of gray matter
      followed by adolescent declines, functional and structural increases in
      connectivity and integrative processing, and a changing balance between
      limbic/subcortical and frontal lobe functions, which extends well into young
      adulthood. Twin studies have demonstrated that genetic factors are responsible
      for a significant amount of variation in pediatric brain morphometry.
      Longitudinal studies have shown specific genetic polymorphisms affect rates of
      cortical changes associated with maturation. Although over-interpretation and
      premature application of neuroimaging findings for diagnostic purposes remains a
      risk, converging data from multiple imaging modalities is beginning to elucidate
      the influences of genetic factors on brain development and implications of
      maturational changes for cognition, emotion, and behavior.

PMID- 21069469
TI  - The American Society of Peritoneal Surface Malignancies (ASPSM).

PMID- 21069471
TI  - Automated mechanical ventilation: adapting decision making to different disease
      states.
AB  - The purpose of the present study is to introduce a novel methodology for adapting
      and upgrading decision-making strategies concerning mechanical ventilation with
      respect to different disease states into our fuzzy-based expert system, AUTOPILOT
      BT. The special features are: (1) Extraction of clinical knowledge in analogy to
      the daily routine. (2) An automated process to obtain the required information
      and to create fuzzy sets. (3) The controller employs the derived fuzzy rules to
      achieve the desired ventilation status. For demonstration this study focuses
      exclusively on the control of arterial CO(2) partial pressure (p(a)CO(2)).
      Clinical knowledge from 61 anesthesiologists was acquired using a questionnaire
      from which different disease-specific fuzzy sets were generated to control
      p(a)CO(2). For both, patients with healthy lung and with acute respiratory
      distress syndrome (ARDS) the fuzzy sets show different shapes. The fuzzy set
      "normal", i.e., "target p(a)CO(2) area", ranges from 35 to 39 mmHg for healthy
      lungs and from 39 to 43 mmHg for ARDS lungs. With the new fuzzy sets our
      AUTOPILOT-BT reaches the target p(a)CO(2) within maximal three consecutive
      changes of ventilator settings. Thus, clinical knowledge can be extended,
      updated, and the resulting mechanical ventilation therapies can be individually
      adapted, analyzed, and evaluated.

PMID- 21069472
TI  - Rapid quantitative analysis of lipids using a colorimetric method in a microplate
      format.
AB  - A colorimetric sulfo-phospho-vanillin (SPV) method was developed for high
      throughput analysis of total lipids. The developed method uses a reaction mixture
      that is maintained in a 96-well microplate throughout the entire assay. The new
      assay provides the following advantages over other methods of lipid measurement:
      (1) background absorbance can be easily corrected for each well, (2) there is
      less risk of handling and transferring sulfuric acid contained in reaction
      mixtures, (3) color develops more consistently providing more accurate
      measurement of absorbance, and (4) the assay can be used for quantitative
      measurement of lipids extracted from a wide variety of sources. Unlike other
      spectrophotometric approaches that use fluorescent dyes, the optimal spectra and
      reaction conditions for the developed assay do not vary with the sample source.
      The developed method was used to measure lipids in extracts from four strains of
      microalgae. No significant difference was found in lipid determination when lipid
      content was measured using the new method and compared to results obtained using
      a macro-gravimetric method.

PMID- 21069473
TI  - Laparoscopic appendectomy for Amyand's hernia: a modern approach to a historic
      diagnosis.
AB  - OBJECTIVES: This study seeks to discuss the management and diagnosis of Amyand's
      hernia, an exceedingly rare diagnosis. METHODS: The case of a 60-year-old female
      found to have inguinal appendicitis on preoperative computed tomography imaging
      is presented. RESULTS: The patient underwent concomitant laparoscopic inguinal
      hernia repair and appendectomy. DISCUSSION: Laparoscopic management of Amyand's
      hernia should be strongly considered for repair and resection.

PMID- 21069474
TI  - Production of lactate in Escherichia coli by redox regulation genetically and
      physiologically.
AB  - Escherichia coli grows fermentatively in glucose-containing medium under
      anaerobic condition with formation of a mixture of organic acids (lactate,
      acetate, formate, and succinate) and ethanol to accommodate reducing equivalents
      generated during glycolysis. In this paper, we tried to improve the lactate
      accumulation in E. coli by redox regulation genetically and physiologically. Our
      results indicated that genetic regulation of the host by reducing the reductive
      by-product may improve the lactate production. In addition, lactate accumulation
      was also improved under reduced and anaerobic cultivation conditions. Engineered
      E. coli SDU4 was able to accumulate lactate under strictly anaerobic conditions
      to 100 g/L with a yield of 1.97 mol/mol glucose.

PMID- 21069476
TI  - COX-2 Gene increases tongue cancer cell proliferation and invasion through VEGF-C
      pathway.
AB  - COX-2 induces the proliferation and invasion of oral squamous cell carcinoma. In
      the present study, the role of the COX-2 gene in the tongue cancer cell
      proliferation and invasion was investigated. A short hairpin RNA (shRNA)method
      was used to knock down COX-2 gene expression and investigate the relationship
      between COX-2 and VEGF-C, and the role of the COX-2 gene for proliferation and
      invasion was also investigated in the tongue cancer cell Tca8113. COX-2 gene
      overexpressed in tongue cancer cell line. Suppressing the expression of COX-2 by
      shRNA could decrease cell proliferation comparing with control shRNA.
      Nevertheless, depressing COX-2 gene expression by shRNA reduced VEGF-C expression
      on both mRNA and protein levels. VEGF-C gene expression could be regulated by COX
      2 gene. Our results suggested that COX-2 played essential roles in the
      proliferation and metastasis of tongue cancer, and COX-2 could serve as a
      potential chemotherapy target for tongue cancer.

PMID- 21069475
TI  - A new generation fatty acid amide hydrolase inhibitor protects against kainate
      induced excitotoxicity.
AB  - Endocannabinoids, including anandamide (AEA), have been implicated in
      neuroprotective on-demand responses. Related to such a response to injury, an
      excitotoxic kainic acid (KA) injection (i.p.) was found to increase AEA levels in
      the brain. To modulate the endocannabinoid response during events of
      excitotoxicity in vitro and in vivo, we utilized a new generation compound
      (AM5206) that selectively inhibits the AEA deactivating enzyme fatty acid amide
      hydrolase (FAAH). KA caused calpain-mediated spectrin breakdown, declines in
      synaptic markers, and disruption of neuronal integrity in cultured hippocampal
      slices. FAAH inhibition with AM5206 protected against the neurodegenerative
      cascade assessed in the slice model 24 h postinsult. In vivo, KA administration
      induced seizures and the same neurodegenerative events exhibited in vitro. When
      AM5206 was injected immediately after KA in rats, the seizure scores were
      markedly reduced as were levels of cytoskeletal damage and synaptic protein
      decline. The pre- and postsynaptic proteins were protected by the FAAH inhibitor
      to levels comparable to those found in healthy control brains. These data support
      the idea that endocannabinoids are released and converge on pro-survival pathways
      that prevent excitotoxic progression.

PMID- 21069477
TI  - Long-term survey of outcome in acute promyelocytic leukemia: a single center
      experience in 340 patients.
AB  - The aims of this study are to investigate the outcome and prognostic factors
      influencing long-term survival on patients with acute promyelocytic leukemia
      (APL). A total of 340 APL patients admitted to the Department of Hematology from
      January 1988 to December 2009 were enrolled in this study. All patients received
      all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) with anthracycline
      based induction therapy. After three courses of consolidation chemotherapy, 279
      patients received 2 years of maintenance therapy. Survival analyses were carried
      out using the Kaplan-Meier method and the Cox regression model. In total, 288
      achieved CR with the CR rate of 84.7%, and 50 patients died during induction
      therapy. Univariate analysis identified the following three risk factors for
      hemorrhagic mortality: fibrinogen level (<1.0 g/l) (P = 0.0007), initial
      peripheral WBC count(>4 * 10(9)/l) (P = 0.0001), as well as the presence of
      coagulopathy(P < 0.0001). With a median follow-up of 49 (6-255) months, the
      estimated 5-year overall survival (OS) and relapse-free survival (RFS) were (89.0
      +/- 2.4)% and (83.7 +/- 2.6)%, respectively. Cox regression analysis of the 290
      patients showed initial WBC count, years of diagnosis, and the status of PML
      RARalpha in remission seemed to be independent prognostic indicators for OS and
      RFS (P = 0.03, P < 0.01 and P = 0.0001, respectively). Cytogenetics in addition
      to above three variables remained significant for RFS (P = 0.01). Our
      retrospective observations suggest that the combination of ATRA and/or ATO with
      anthracycline-based therapy may have useful implications in the perspective of
      long-term prognosis for adult APL.

PMID- 21069479
TI  - Oxymatrine diminishes the side population and inhibits the expression of beta
      catenin in MCF-7 breast cancer cells.
AB  - Cancer stem cells (CSCs) play a critical role in both cancer initiation and
      relapse as they are resistant to most cytotoxic agents and able to proliferate
      indefinitely. The plant alkaloid oxymatrine has many biological activities
      including the ability to induce cell cycle arrest and apoptosis, which makes it a
      potentially useful agent for targeting cancer cells. In order to determine
      whether it has beneficial pharmacological properties to eradicate CSCs, we
      analyzed the effects of oxymatrine on MCF-7 breast cancer cells. Cancer stem-like
      cells' (side population, SP) identification and sorting were performed. The
      inhibitory effect of oxymatrine was evaluated on the sorted SP and non-SP cells.
      The results indicated that oxymatrine caused a dose-dependent reduction in the
      proliferation of MCF-7 cells and a decrease in SP cells. Wnt/beta-catenin
      signaling pathway was also examined by analyzing the expression of total beta
      catenin and phosphorylated beta-catenin in cytoplasm, and the results showed that
      the growth inhibitory effects of oxymatrine treatment on MCF-7 cells may be due
      to the inhibition of SP and Wnt/beta-catenin signaling pathway. Further work is
      warranted to explore whether oxymatrine may be a useful novel therapeutic drug
      for targeting breast CSCs.

PMID- 21069480
TI  - AXIN2 polymorphism and its association with prostate cancer in a Turkish
      population.
AB  - Polymorphism of AXIN2, a component of Wnt signaling, has been shown to play a
      role in tumorigenesis and dysregulated in cancer cells. In order to find out if
      AXIN2 polymorphism is a risk factor for prostate cancer, we analyzed eight
      polymorphic regions of this gene in 84 patients with prostate cancer and compared
      the results with 100 healthy controls in a Turkish population using PCR-RFLP
      methods. The genotype frequencies and risk factors of prostate cancer and control
      groups were analyzed by Chi-square test. We found a statistically significant
      result between prostate cancer risk and AXIN2 Intron2-956+16A/G (rs35285779) SNP.
      The frequency of the homozygous G/G (0%) and heterozygous A/G (18%) genotypes was
      significantly less in patients with prostate cancer than in healthy controls (7
      and 32%, respectively) (P<0.05) for this SNP. When compared with the wild-type
      A/A genotype of the controls, prostate cancer patients with the A/G and G/G
      genotype showed reduced risk of cancer; the adjusted odds ratio (OR) for patients
      with the homozygous G/G genotype was 0.87 (95% CI: 0.81-0.95) and for
      heterozygous A/G genotype was 0.42 (95% CI: 0.20-0.85). We found no statistically
      significant association between controls and prostate cancer for other seven SNPs
      of AXIN2 including Exon1-148 C/T (rs2240308), Exon1-432 T/C (rs2240308), Exon5
      1365 G/A (rs9915936), Exon5-1386 C/T (rs1133683), Intron5-1712+19 T/G, Exon7-2062
      C/T, and Intron7-2141+73 G/A (rs4072245) (P>0.05). These results suggest that the
      AXIN2 Intron2 rs35285779 SNP is associated with development of prostate cancer as
      a protective SNP, while an association between other seven SNPs of the AXIN2 and
      risk of prostate cancer was not observed.

PMID- 21069481
TI  - Blood stain pattern analysis.
AB  - Bloodstain pattern analysis (BPA) refers to the collection, categorization and
      interpretation of the shape and distribution of bloodstains connected with a
      crime. These kinds of stains occur in a considerable proportion of homicide
      cases. They offer extensive information and are an important part of a
      functional, medically and scientifically based reconstruction of a crime. The
      following groups of patterns can essentially be distinguished: dripped and
      splashed blood, projected blood, impact patterns, cast-off stains, expirated and
      transferred bloodstains. A highly qualified analysis can help to estimate facts
      concerning the location, quality and intensity of an external force. A sequence
      of events may be recognized, and detailed questions connected with the
      reconstruction of the crime might be answered. In some cases, BPA helps to
      distinguish between accident, homicide and suicide or to identify bloodstains
      originating from a perpetrator. BPA is based on systematic training, a visit to
      the crime scene or alternatively good photographic documentation, and an
      understanding and knowledge of autopsy findings or statements made by the
      perpetrator and/or victim. A BPA working group has been established within the
      German Society of Legal Medicine aiming to put the knowledge and practical
      applications of this subdiscipline of forensic science on a wider basis.

PMID- 21069478
TI  - Biochemical, pathological and oncological relevance of Gb3Cer receptor.
AB  - Glycosphingolipids are amphipathic molecules composed of hydrophilic
      oligosaccharide chain and a hydrophobic ceramide part, located primarily in the
      membrane microdomains of animal cells. Their oligosaccharide chains make them
      excellent candidates for the cell surface recognition molecules. Natural
      glycosphingolipid, globotriaosylceramide (Gal alpha1-4, Gal beta1-4, Glc beta1-1,
      ceramide), is also called CD77 and its expression was previously associated with
      proliferating centroblasts undergoing somatic hypermutation, but it has been
      demonstrate that globotriaosylceramide is not a reliable marker to discriminate
      human centroblasts from centrocytes. Globotriaosylceramide constitutes rare P k
      blood group antigen on erythrocytes, and it is also known as Burkitt's lymphoma
      antigen. On endothelial cells, globotriaosylceramide plays as the receptor for
      bacterial toxins of the Shiga family, also called verotoxins. Precise biological
      function and significance of globotriaosylceramide expression on endothelial
      cells remains to be the subject of many studies and it is believed
      globotriaosylceramide represents an example of a glycolipid antigen able to
      transduce a signal leading to apoptosis. In past decade, cancer researches put a
      great afford in determining new therapeutic agents such as bacterial toxins
      against tumor malignancies. Reports have demonstrated that verotoxin-1 induces
      apoptosis in solid tumor cell lines expressing globotriaosylceramide such as
      astrocytoma, renal cell carcinoma, colon cancer and breast cancer due to
      verotoxin-1 high specificity and apoptosis-inducing properties, and therefore, it
      is suggested to be an anticancer agent. Verotoxins have been investigated weather
      they could reduce treatment side-effects and toxicity to normal tissues and
      become a new oncological tool in cancer labeling.

PMID- 21069482
TI  - Cardiovascular risk reduction via increasing HDL cholesterol: the promise of the
      dal-OUTCOMES Trial.

PMID- 21069484
TI  - Backbone, side chain and heme resonance assignments of the triheme cytochrome
      PpcA from Geobacter sulfurreducens.
AB  - Gene knock-out studies on Geobacter sulfurreducens cells showed that the
      periplasmic triheme cytochrome PpcA is involved in respiratory pathways leading
      to the extracellular reduction of Fe(III) and U(VI) oxides. The crucial role of
      this protein in bridging the electron transfer between the cytoplasm and cell
      exterior was further supported by proteomics studies. In comparison with non-heme
      proteins, the presence of numerous proton-containing groups in the heme groups
      causes additional challenges to the full protein assignment and structure
      calculation. Here, we report the complete assignment of the heme proton signals
      together with the (1)H and (15)N backbone and side chain assignments of the
      reduced form of PpcA.

PMID- 21069483
TI  - Sleep apnea and diabetes: insights into the emerging epidemic.
AB  - The rampant diabetes pandemic over the past few decades has been associated with
      an increased rise in cardiovascular events and deaths. Risk factors such as
      obesity, family history of diabetes, decreased physical activity, and aging are
      among the most common in the development of diabetes. Emerging evidence in the
      past 10 years has suggested that sleep apnea is a novel risk factor in the
      development of diabetes. Associations between diabetes and sleep apnea are
      supported by both epidemiologic and clinical sleep apnea studies. In this report,
      we discuss epidemiologic and clinical evidence suggesting that sleep apnea is
      involved in the pathogenesis of altered glucose metabolism. In light of current
      evidence, sleep apnea treatment should be incorporated into existing
      pharmacotherapeutic regimens for optimal management of diabetes among diabetic
      patients with sleep apnea to reduce associated cardiovascular risk. Suggestions
      to improve practice guidelines in the management of diabetic patients with sleep
      apnea are provided.

PMID- 21069485
TI  - 100% complete assignment of non-labile (1)H, (13)C, and (15)N signals for calcium
      loaded Calbindin D(9k) P43G.
AB  - Here we present the 100% complete assignment chemical shift of non-labile (1)H,
      (15)N and (13)C nuclei of Calbindin D(9k) P43G. The assignment includes all non
      exchangeable side chain nuclei, including ones that are rarely reported, such as
      LysNzeta as well as the termini. NMR experiments required to achieve truly
      complete assignments are discussed. To the best of our knowledge our assignments
      for Calbindin D(9k) extend beyond previous studies reaching near-completeness
      (Vis et al. in Biochem 33:14858-14870, 1994; Yamazaki et al. in J Am Chem Soc
      116:6464-6465, 1994; Yamazaki et al. in Biochem 32:5656-5669, 1993b).

PMID- 21069486
TI  - Can reverse shoulder arthroplasty be used with few complications in rheumatoid
      arthritis?
AB  - BACKGROUND: Many patients with rheumatoid arthritis develop superior migration of
      the humeral head because of massive cuff tears, causing loss of active motion.
      Reverse shoulder arthroplasty could potentially restore biomechanical balance but
      a high incidence of glenoid failure has been reported. These studies do not,
      however, typically include many patients with rheumatoid arthritis (RA) and it is
      unclear whether the failure rates are similar. QUESTIONS/PURPOSES: We therefore
      (1) evaluated pain relief and shoulder function after reverse arthroplasty in RA;
      (2) compared results between primary and revision procedures; (3) determined the
      incidence of scapular notching; and (4) determined the complication rate.
      METHODS: We identified 29 patients with RA who had 33 reverse arthroplasties from
      among 412 patients having the surgery. Six patients were lost to followup. Twenty
      three patients (27 shoulders) were evaluated after a minimum followup of 18
      months (mean, 56 months; range, 18-143 months), including 18 primary and nine
      revision arthroplasties. All patients were evaluated preoperatively and 23
      shoulders postoperatively by an independent physiotherapist and four were
      assessed postoperatively by phone. Level of pain, range of motion, and Constant
      Murley score were recorded and new radiographs taken. RESULTS: Visual Analog
      Scale score for pain decreased from 8.0 to 1.0. Constant-Murley score increased
      from 13 to 52. Primary procedures had higher scores compared with revisions.
      Three patients had revision surgery. Notching occurred in 52% of shoulders but no
      loosening was seen. CONCLUSIONS: Reverse arthroplasty in rheumatoid arthritis
      improved shoulder function with a low incidence of complications. We believe it
      should be considered in elderly patients with rheumatoid arthritis with pain and
      poor active range of motion resulting from massive cuff tears. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 21069487
TI  - Supraspinatus and infraspinatus weakness in overhead athletes with scapular
      dyskinesis: strength assessment before and after restoration of scapular
      musculature balance.
AB  - A disturbance in scapulohumeral rhythm may cause negative biomechanic effects on
      rotator cuff (RC). Alteration in scapular motion and shoulder pain can influence
      RC strength. Purpose of this study was to assess supraspinatus and infraspinatus
      strength in 29 overhead athletes with scapular dyskinesis, before and after 3 and
      6 months of rehabilitation aimed to restore scapular musculature balance. A
      passive posterior soft tissues stretching was prescribed to balance shoulder
      mobility. Scapular dyskinesis patterns were evaluated according to Kibler et al.
      Clinical assessment was performed with the empty can (EC) test and infraspinatus
      strength test (IST). Strength values were recorded by a dynamometer; scores for
      pain were assessed with VAS scale. Changes of shoulder IR were measured. The
      force values increased at 3 months (P < 0.01) and at 6 months (P < 0.01). Changes
      of glenohumeral IR and decrease in pain scores were found at both follow-up.
      Outcomes registered on pain and strength confirm the role of a proper scapular
      position for an optimal length-tension relationship of the RC muscles. These data
      should encourage those caring for athletes to consider restoring of scapular
      musculature balance as essential part of the athletic training.

PMID- 21069488
TI  - The role of myocardial perfusion imaging in evaluating patients with myocardial
      bridging.
AB  - BACKGROUND: Myocardial bridging (MB) is a common, congenital coronary-abnormality
      that is found on average in one out of every three adults at autopsy (Moehlenkamp
      et al in Circulation, 106:2616-2622, 2002; Erbel et al in Circulation, 120:357
      359, 2009). However, its clinical significance and impact on myocardial ischemia
      remains controversial and unclear. Myocardial perfusion imaging (MPI) is widely
      used to assess myocardial ischemia in patients with known or suspected coronary
      artery disease, and is frequently performed to evaluate the hemodynamic
      significance of MB. This study was undertaken to determine the use of MPI in
      evaluating MB and to identify the characteristics of MB associated with perfusion
      defects using MPI. METHODS AND RESULTS: Thirty-nine patients with MB of the left
      anterior descending (LAD) artery as documented by coronary angiography (CA) were
      enrolled for this study. None of the patients exhibited other forms of heart
      disease as determined by both CA and stress-rest MPI, no later than 1 month prior
      to the study. Using MPI, eight patients (20.5%) were found to have perfusion
      defects in the corresponding myocardial areas. This frequency was significantly
      higher when compared with results obtained by stress electrocardiogram. The
      difference in the mean systolic narrowing of bridging segments was statistically
      significant between patients with and without ischemia. The positive rate of
      reversible defects in patients with severe systolic narrowing was significantly
      higher than in patients with mild-to-moderate systolic narrowing. However, there
      was no significant difference either between the mean length of the tunneled
      artery in patients with and without abnormal MPI or the positive rate of abnormal
      MPI in patients with different locations of the tunneled artery. CONCLUSIONS: MPI
      is an effective, noninvasive technique for the evaluation of patients with MB.
      The myocardial ischemia that resulted from bridging is associated more closely
      with the degree of systolic narrowing than with the length of tunneled artery or
      the location of MB.

PMID- 21069489
TI  - Reduced isotope dose with rapid SPECT MPI imaging: initial experience with a CZT
      SPECT camera.
AB  - BACKGROUND: Cardiac SPECT imaging needs to become shorter and use lower radiation
      doses to compete with other available noninvasive imaging modalities. Recently
      introduced cadmium zinc telluride (CZT) SPECT cameras have the potential to
      achieve both goals, but clinical experience is so far limited. METHODS: Images of
      all patients undergoing a stress MPI over a 4-month period using a CZT camera
      (Discovery NM 530c) were reviewed. Patients were divided into three groups based
      on imaging protocols: low-dose stress-only, high-dose stress-only, and standard
      dose rest-stress. Low-dose stress-only patients were matched by gender, stressor,
      and BMI to high-dose stress-only and rest-stress subjects. Stress image quality
      was graded on a four-point scale by readers blinded to the imaging protocol.
      Demographics, tracer dose, stress imaging time, and total counts were recorded.
      RESULTS: Of 717 patients imaged, the mean age was 64.0 years, 50.5% were female,
      58.9% underwent exercise stress, and the average BMI was 27.9 kg/m(2). A total of
      103 low-dose stress-only patients were matched to controls. Imaging for 5 minutes
      in low-dose stress-only patients and for 3 minutes in high-dose stress-only and
      rest-stress patients, resulted in a similar number of total counts. This produced
      similar image quality in the three groups with a 57% isotope dose reduction in
      the low-dose stress-only compared to the high-dose stress-only group. CONCLUSION:
      New SPECT CZT camera technology allows significantly reduced radiation exposure
      and acquisition time without loss of image quality.

PMID- 21069490
TI  - Both stereoselective (R)- and (S)-1-Methyl-1,2,3,4-tetrahydroisoquinoline
      enantiomers protect striatal terminals against rotenone-induced suppression of
      dopamine release.
AB  - 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is present in the human and
      rodent brain as a mixture of stereospecific (R)- and (S)-1MeTIQ enantiomers. The
      racemate, (R,S)-1MeTIQ, exhibits neuroprotective activity as shown in the earlier
      study by the authors, and In addition, it was suggested to play a crucial
      physiological role in the mammalian brain as an endogenous regulator of
      dopaminergic activity. In this article, we investigated the influence of
      stereospecific enantiomers of 1MeTIQ, (R)- and (S)-1MeTIQ (50 mg/kg i.p.) on
      rotenone-induced (3 mg/kg s.c.) behavioral and neurochemical changes in the rat.
      In behavioral study, in order to record dynamic motor function of rats, we
      measured locomotor activity using automated locomotor activity boxes. In
      biochemical studies, we analyzed in rat striatum the concentration of dopamine
      (DA) and its metabolites: intraneuronal DOPAC, extraneuronal 3-MT, and final HVA
      using HPLC with electrochemical detection. Otherwise, DA release was estimated by
      in vivo microdialysis study. The behavioral study has demonstrated that both
      acute and repeated (3 times) rotenone administration unimportantly depressed a
      basic locomotor activity in rat. (R)- and (S)-1MeTIQ stereoisomers (50 mg/kg
      i.p.) produced a modest behavioral activation both in naive and rotenone-treated
      rats. The data from ex vivo neurochemical experiments have shown
      stereospecificity of 1MeTIQ enantiomers in respect of their effects on DA
      catabolism. (R)-1MeTIQ significantly increased both the level of the final DA
      metabolite, HVA (by about 70%), and the rate of DA metabolism (by 50%). In
      contrast to that, (S)-1MeTIQ significantly depressed DOPAC, HVA levels (by 60 and
      40%, respectively), and attenuated the rate of DA metabolism (by about 60%). On
      the other hand, both the enantiomers increased the concentrations of DA and its
      extraneuronal metabolite, 3-MT in rat striatum. In vivo microdialysis study has
      shown that repeated but not acute administration of rotenone produced a deep and
      significant functional impairment of striatal DA release. Both (R)- and (S)-
      stereospecific enantiomers of 1MeTIQ antagonized rotenone-induced suppression of
      DA release; however, the effect of (R)-1MeTIQ was more strongly expressed in
      microdialysis study. In conclusion, we suggest that both chiral isomers of 1MeTIQ
      offer neuroprotection against rotenone-induced disturbances in the function of
      dopaminergic neurons and (R,S)-1MeTIQ will be useful as a drug with marked
      neuroprotective activity in the brain.

PMID- 21069491
TI  - High-pressure decisions: recognition and management of uncommon hand injuries.

PMID- 21069492
TI  - The first author h-index (h(fa)-index): levelling the field for small and large
      institute medical and science scholars.

PMID- 21069493
TI  - Double patch technique for closing acute ventricular septal perforation.
AB  - PURPOSE: Ventricular septal perforation (VSP) is a rare but life-threatening
      complication of acute myocardial infarction (AMI). Even with assisted circulation
      heart failure often progresses quickly, and urgent surgical intervention is
      required to close the VSP. For several years, we have been performing a double
      patch closure technique using an equine pericardial patch. In this report, we
      present details of our patch closure technique and the VSP surgical results; we
      also examine the problems we encountered. METHODS: The present study was a review
      of nine patients who underwent our patch closure of VSP secondary to AMI. We used
      a large double-layered equine pericardial patch to close the VSP and did not
      exclude the infarction area from the left ventricular cavity. No necrotic
      myocardium was excised to avoid simultaneous excision of stunned myocardium.
      RESULTS: No patients died within 30 days of the surgery, and there were no in
      hospital deaths. Over a mean clinical follow-up period of 4.5 years, no residual
      shunts were detected, and all patients were alive and had New York Heart
      Association functional class II. CONCLUSION: Our patch closure technique was
      effective for closing VSPs securely. The operating times and cardiopulmonary
      bypass times were short, and blood loss was minimal. Our patch closure technique
      may improve the prognosis of VSP.

PMID- 21069494
TI  - Short-term and long-term outcomes of octogenarians after off-pump coronary artery
      bypass surgery.
AB  - PURPOSE: Off-pump coronary artery bypass has been reported to be associated with
      reduced morbidity and mortality after surgical coronary revascularization,
      especially in high-risk patients. The aim of this study was to clarify the
      efficacy of off-pump coronary artery bypass for the very elderly patients.
      METHODS: We compared the outcomes of octogenarians (n = 28, 82 +/- 2 years)
      undergoing off-pump coronary artery bypass and those of the patients <80 years of
      age (n = 315, 67 +/- 9 years) during short- and long-term periods. RESULTS: There
      was no difference in hospital mortality between octogenarians and the younger
      cohort (3.8% vs. 0.6%; P = 0.11). A high rate of postoperative complications
      (e.g., pneumonia, transient renal dysfunction, ventricular arrhythmia) were
      observed in the octogenarians. The long-term survival (81% at 5 years) and the
      rate of freedom from cardiac death (92% at 5 years) and from cardiac events (85%
      at 5 years) were excellent in the octogenarians; they appeared less favorable,
      however, when compared with the younger group (95%, 98%, and 94% at 5 years,
      respectively). Most of the cardiac adverse events, including unexplained sudden
      death, occurred 6 months after the surgery in octogenarians. CONCLUSION: Off-pump
      coronary artery bypass can be performed safely in octogenarians, with excellent
      early and late outcomes. Careful postoperative follow-up is required to reduce
      postoperative long-term adverse events. Off-pump coronary artery bypass is a
      feasible modality of coronary revascularization for octogenarians.

PMID- 21069495
TI  - Early results of minimally invasive mitral valve surgery: initial series in a
      public hospital in Australia.
AB  - PURPOSE: This study analyzes the initial experience with minimally invasive
      mitral valve surgery through a right minithoracotomy in a public teaching
      hospital in Australia and evaluates early surgical outcomes. METHODS: A
      retrospective review of patients who underwent minimally invasive mitral valve
      surgery between November 2006 and March 2009 was performed. RESULTS: A total of
      60 patients included 47 (78%) patients who had mitral valve plasty and 13 (22%)
      who had mitral valve replacement. The mean age was 61 +/- 15 years; 33 (55%)
      patients were male; and 6 (10%) had had previous cardiac operations. The mean
      cardiopulmonary bypass and aortic cross-clamp times were 140 +/- 46 and 93 +/- 35
      min, respectively. All patients who underwent mitral valve plasty left the
      operation room with no more than trivial residual mitral regurgitation. There was
      no operative mortality. Reoperation for bleeding and stroke occurred in 2
      patients each. The mean intensive care unit and hospital stays were 3.1 +/- 5.8
      and 10.6 +/- 8.9 days, respectively. Among the 47 patients with mitral valve
      plasty, 46 (98%) had mild or less mitral regurgitation on transthoracic
      echocardiography at discharge. There was one late death. No reoperation for the
      mitral valve has been observed so far. An echocardiography report was obtained
      for 34 of the 47 who had had mitral valve plasty at 12.1 +/- 7.9 months
      postoperatively, and 27 (79%) of them had mild or less mitral regurgitation.
      CONCLUSION: Minimally invasive mitral valve surgery through a right
      minithoracotomy was safely performed with no early mortality.

PMID- 21069496
TI  - Prognostic significance of the combined use of preoperative platelet count and
      serum carcinoembryonic antigen level in non-small-cell lung cancer.
AB  - PURPOSE: The prognostic significance of the combined use of preoperative platelet
      count and serum carcinoembryonic antigen (CEA) level in non-small-cell lung
      cancer patients was investigated. METHODS: Consecutive 289 non-small-cell lung
      cancer patients were reviewed retrospectively. Thrombocytosis was defined as a
      platelet count of at least 40 * 10(4)/mm(3). RESULTS: The frequency of
      preoperative thrombocytosis was 4.5% (13/289). The 5-year survival of patients
      with thrombocytosis was 30.77%, which was significantly poorer than that of
      patients with normal counts (68.65%, P = 0.0010). The 5-year survivals of
      patients with a normal CEA level and those with an elevated serum CEA level were
      74.18% and 55.78%, respectively (P = 0.0019). Patients with both a normal
      platelet count and a normal serum CEA level had a favorable prognosis, whereas
      those with both thrombocytosis and elevated serum CEA level had a poor prognosis.
      The prognostic impact of the combined use of the platelet count and the serum CEA
      level was more significant than that of the platelet count or the serum CEA level
      alone. Both univariate and multivariate analyses indicated an independent
      prognostic impact of the combined use of platelet count and serum CEA levels.
      CONCLUSION: The combined use of preoperative platelet count and serum CEA levels
      might be useful for predicting the prognosis of non-small-cell lung cancer
      patients.

PMID- 21069497
TI  - Total circulatory arrest: a life-saving procedure for mediastinoscopic major
      hemorrhage.
AB  - Acute hemorrhage during mediastinoscopy is a life-threatening complication.
      Although rare, iatrogenic damage of the thoracic great vessels is probable during
      mediastinoscopic biopsy. We report two cases of iatrogenic massive
      mediastinoscopic bleeding from the aortic arch and innominate artery managed
      initially by simple packing and controlled finally by cardiopulmonary bypass and
      repair under total circulatory arrest.

PMID- 21069498
TI  - Herpes simplex virus pneumonia following mitral valve replacement.
AB  - We describe a rare case of a 79-year-old woman who developed herpes simplex virus
      pneumonia after mitral valve replacement. The patient showed persistent hypoxemia
      with bilateral glass-like shadows on chest radiography. Cytopathology examination
      of intratracheal secretions revealed herpes simplex virus infection. The patient,
      who improved gradually after acyclovir administration, was taken off the
      ventilator completely. Physicians should consider viral pulmonary infection to be
      a potential cause of unexplained hypoxemia that does not respond to conventional
      antibiotic treatment in critically ill, immunocompromised patients.

PMID- 21069499
TI  - Successful treatment for descending necrotizing mediastinitis with severe
      thoracic emphysema using video-assisted thoracoscopic surgery.
AB  - Descending necrotizing mediastinitis (DNM) is a rare, highly fatal disease that
      occurs as a complication of a cervical or odontogenic infection spreading into
      the mediastinum. We herein report of a 50-year-old man with DNM and severe
      thoracic emphysema who was successfully treated using surgical drainage by video
      assisted thoracoscopic surgery (VATS) and a transcervical approach. Chest
      enhanced computed tomography on admission revealed massive left pleural effusion,
      pneumothorax, absolute collapse of the left lung, and a mediastinal shift to the
      right side with emphysema. We urgently performed left thoracic and mediastinal
      drainage using VATS. Retropharyngeal and upper mediastinal drainage was performed
      transcervically on the third hospital day. He recovered and was discharged on
      hospital day 57. Surgical drainage is the most important therapy in the treatment
      of DNM, but there is no standard surgical approach. We believe that VATS is a
      less invasive, effective modality for draining the posterior mediastinum.

PMID- 21069500
TI  - Resected osteochondroma of the rib in an elderly patient.
AB  - Solitary osteochondroma of the rib is a rare primary chest wall tumor. Herein, we
      report a case of a successfully resected osteochondroma of the rib. The patient
      was a 73-year-old asymptomatic woman who came to our hospital regularly for
      treatment of hypertension and hyperlipidemia. A checkup chest roentgenogram
      showed a shadow at the right anterior chest wall consistent with a mass, and
      computed tomography showed a tumor arising from the right fourth rib. Because it
      was impossible to exclude completely the diagnosis of a well-differentiated
      chondrosarcoma, we performed resection of the right anterior chest wall and a re
      construction with a rigid prosthesis. The post operative course of the patient
      was unremarkable. The final pathological diagnosis of the rib tumor was
      osteochondroma.

PMID- 21069501
TI  - Cuff-preserving technique for aortic mechanical artificial valve replacement
      performed for perivalvular leakage.
AB  - We present a new, less-invasive technique for a re-do for perivalvular leakage
      after aortic mechanical valve replacement. Only the carbon ring of the previously
      implanted St. Jude prosthesis was excised, the sewing cuff being preserved. The
      locations of the perivalvular defects were clearly identified by pulling the
      sewing cuff inward. They were securely closed by placing pledgeted sutures at the
      preserved cuff through the full thickness of the aortic wall or through the
      annulus by a deep bite from the left ventricular side. A new mechanical
      prosthesis was then sewn onto the preserved sewing cuff.

PMID- 21069502
TI  - Effective and rapid technique to ensure uniform talc pleurodesis.
AB  - The use of talc for inducing chemical sclerosis in the pleural cavity dates back
      to 1935. Insufflation (also known as talc poudrage) and instillation have been
      the techniques used for administering talc. We describe a surgical technique to
      insufflate talc in the pleural cavity using an ingenious method at no additional
      cost that ensures effective, widespread talc dispersion and good results.

PMID- 21069503
TI  - [Pigmented lesion on the temple. Pigment cell tumor, basal cell carcinoma, or
      irritated seborrheic keratosis?].
AB  - 33-year-old woman with a red-brown plaque on the temple. The slightly raised skin
      tumor with well-defined margins had appeared 3 years earlier, slowly enlarging
      and finally changing in color. Digital enhancement revealed a vascular pattern
      with hairpin-like and twisted fine capillaries. Often, there were light halos and
      slate-gray granules (melanophages) around the vessels. Biopsy of the tumor
      demonstrated hyperplasia of the epidermis and normal basaloid keratinocytes
      partially extending into the dermis. Inflammatory cells and melanophages were
      present in the papillary dermis, surrounding dilated vessels. Histopathological
      diagnosis revealed an irritated seborrheic keratosis.

PMID- 21069505
TI  - [New oral anticoagulants from the perspective of trauma surgery].
AB  - Heparins and vitamin K antagonists have been the cornerstones of anticoagulation
      therapy for several decades. While these compounds have proven to be effective at
      inhibiting the coagulation process, they have inherent limitations. This has
      spurred efforts to develop therapies that will overcome these drawbacks while
      matching the efficacy of the conventional anticoagulants. Significant advances
      have been made in the development of more specific treatments targeting factor Xa
      or thrombin and providing more predictable anticoagulant responses. They also
      offer the convenience of oral administration with fixed dose regimens not
      requiring routine monitoring which may have an impact on compliance. The factor
      Xa inhibitor rivaroxaban and the thrombin inhibitor dabigatran etexilate have
      become available for prevention of venous thromboembolism after elective hip and
      knee replacement surgery and registration of the factor Xa inhibitor apixaban is
      expected to occur soon. Furthermore, first clinical evidence has become available
      for all of these compounds in patients requiring long-term anticoagulation. It is
      to be expected that these results will lead to improvements in prevention of
      stroke in patients with atrial fibrillation and in treatment of venous
      thromboembolism.

PMID- 21069506
TI  - [Thromboembolism prophylaxis in trauma surgery: S3 guidelines and significance of
      the amendment for trauma surgeons].
AB  - Prevention of venous thromboembolism has become an integral component of trauma
      surgery treatment and consists of physical and pharmacological measures. The
      indications and choice of prophylaxis modalities depend on the patient's
      individual risk profile which is determined by the combination of exposing and
      predisposing risk factors. The exposing risk is characterized by the type and
      extent of surgery or trauma, whereas the predisposing risk relates to patient
      inherent risk factors. This has also been considered in the compilation of the
      guidelines. This review summarizes the recommendations of the German S3
      guidelines relating to trauma surgery and also discusses the amendment referring
      to the registration of the new oral anticoagulants rivaroxaban and dabigatran
      etexilate. The availability of these new compounds increases the spectrum of
      prophylaxis modalities thereby creating a need for new information in trauma
      surgery.

PMID- 21069507
TI  - [Bridging, interruption and switching of anticoagulants in trauma surgery].
AB  - Patients under long-term administration of vitamin K antagonists may require
      temporary interruption of anticoagulation therapy for invasive procedures or
      trauma surgery. Due to the long half-life of these substances bridging therapy
      with anticoagulants having a shorter half-life may become necessary. In this
      situation the risk of bleeding due to the intervention and the risk of
      thromboembolism due the underlying disease must be assessed. Low molecular weight
      heparins (LMWHs) are considered to be the medication of choice for bridging
      anticoagulation, mainly due to practical reasons and as they do not require
      coagulation monitoring and dose adjustment out of hospital treatment is feasible.
      Low molecular weight heparins are not authorized for the indication of bridging
      anticoagulation, however, on the basis of recent studies on large patient
      cohorts, the evidence of efficacy and safety is significantly better for LMWHs
      than for unfractionated heparin. New oral anticoagulants will soon become
      available for stroke prevention in patients with atrial fibrillation and for
      treatment of venous thromboembolism. Due to the shorter half-lives these
      compounds will no longer require bridging anticoagulation. However, the trauma
      surgeon should be familiar with the dosing regimens for different indications in
      order to adequately decide about the preoperative cessation and the perioperative
      pause of these anticoagulants.

PMID- 21069508
TI  - [Recommendations for the administration of conventional and new antithrombotic
      agents from the perspective of anesthesiology].
AB  - Neuraxial blockade confers benefits to surgical patients not only due to the high
      analgesic quality but also through a reduction in postoperative complications,
      such as respiratory insufficiency and a shortening of postoperative paralytic
      ileus. In orthopedic surgery peripheral and neuraxial blockades are extensively
      used to enhance postoperative mobilization. The most serious complication of
      neuraxial blockade is spinal epidural hematoma, which may lead to permanent
      paraplegia if left untreated. The risk is enhanced in patients receiving
      thromboembolism prophylaxis. Most national societies have issued guidelines with
      specific time intervals between application of antithrombotic drugs and
      subsequent neuraxial blockade to minimize this risk. From the viewpoint of an
      anesthesiologist it is preferable to start with chemical thromboembolism
      prophylaxis postoperatively as opposed to preoperatively, to administer all drugs
      in the evening and to limit the number of available drugs at each site. The
      safety of neuraxial blockade in the presence of the new oral anticoagulant
      rivaroxaban is currently unknown due to limited experience and dabigatran is
      considered contraindicated with indwelling epidural catheters according to the
      manufacturer.

PMID- 21069509
TI  - [Injuries to the upper cervical spine. Part 1: ligamentous injuries].
AB  - This article for continuing education describes ligamentous injuries of the upper
      cervical spine. Functional radiological imaging studies are particularly
      important in the diagnostic workup. Computed tomography can serve to visualize
      additional osseous traumas and magnetic resonance imaging can demonstrate
      discoligamentous, neuronal, and vascular structures. Traumatic ligamentous
      instabilities of the upper cervical spine can be categorized into four main
      groups: occipitocervical dislocation and translational, axial, and rotational
      atlantoaxial instabilities. The incidence, classification, diagnostic workup,
      standard treatment, and characteristics of the individual ligamentous injuries
      are presented. In addition, the topic of combined injuries of the upper cervical
      spine is addressed.

PMID- 21069511
TI  - [Comparison of dignity determination of mammographic microcalcification with two
      systems for digital full-field mammography with different detector resolution: a
      retrospective clinical study].
AB  - PURPOSE: The aim of this retrospective clinical study was to compare the
      diagnostic accuracy of the novel 50 um FFDM (full-field digital mammography)
      system (DR) with an established 70 um system (DR) in the differential diagnosis
      between benign and malignant clusters of microcalcification (n=50) (BI-RADSTM
      classification 4/5) and to assess the possible incremental value of the 50 um
      pixel-pitch on specificity. MATERIAL AND METHODS: From March 2009 to September
      2009, 50 patients underwent full-field digital mammography (FFDM) (detector
      resolution 70 um) (Novation, Siemens, Erlangen, Germany). As there were
      suspicious signs of microcalcification classified with BI-RADSTM 4/5 after
      diagnosis and preoperative wire localization, control images were made with the
      new FFDM system (detector: resolution 50 um) (Amulet, Fujifilm, Tokyo, Japan)
      with the same exposure parameters. The diagnosis was determined after the
      operation by five radiologists with different experience in digital mammography
      from randomly distributed mediolateral views (monitor reading) whose results were
      correlated with the final histology of all lesions. RESULTS: Histopathology
      revealed 19 benign and 31 malignant lesions in 50 patients after open biopsy. The
      results of the five readers showed a higher sensitivity of the new FFDM system
      (80.0%) in the ability to recognize malignant microcalcification in comparison to
      the established system (74.8%). The specificity (75.8 versus 71.6%) was slightly
      higher for the new system but these results were not statistically significant
      (p<0.001). Considering the diagnostic accuracy, the new system (detector:
      resolution 50 um) was also slightly superior to the well-known system (detector:
      resolution 70 um) (80.1% versus 76.4%). CONCLUSIONS: Our study has shown that the
      new full-field digital mammography system using the novel detector compared with
      the already established FFDM system with respect to the assessment of
      microcalcification is at least equivalent.

PMID- 21069512
TI  - [First experiments for the detection of simulated mammographic lesions: digital
      full field mammography with a new detector with a double plate of pure selenium].
AB  - PURPOSE: The article describes an experimental phantom study of a system for
      digital full field mammography with a new digital detector with a double plate of
      pure selenium. MATERIALS AND METHODS: The experiments were carried out with the
      new full field digital mammography system Amulet from FujiFilm. This system has a
      new detector (18*24 cm(2)) on the basis of highly purified amorphous selenium (a
      Se) with a pixel size of 50 um. The x-rays are converted into electric signals in
      the first plate which are read into the second plate with the help of an optical
      switch and demonstrated in the form of an image. In this way a better pixel
      size/volume and signal-to-noise ratio should be achieved. The object of the
      investigation was the Wisconsin Mammographic Random Phantom, Model 152 A
      (Technical Performance Mo/Mo, 28 kV, 100 mAs). Five investigators with different
      experiences in mammography each received three images on a monitor with different
      random positions of the simulated lesions in the phantom for assessment. The
      detection rates were compared under the same conditions with the results of two
      other full field digital mammography systems. RESULTS: The median detection rate
      for all images and investigators for the new doubled plated a-Se detector with
      optical switch was 98.7%. For both other systems with a-Si or and a-Se detectors
      the detection rate was 89.8% or 97.3%, respectively. There were no significant
      differences in the detection rate of the simulated breast lesions for all three
      systems considering the interobserver and intraobserver variation. CONCLUSION:
      The first phantom study for the detection of simulated breast lesions with the
      new full field digital mammography system Amulet demonstrates equivalent results
      with the other systems used in the clinical routine. The trend towards
      superiority of the new system has to be confirmed in further clinical studies.

PMID- 21069513
TI  - Thank you for 2010.

PMID- 21069514
TI  - Fluoxetine attenuates the inhibitory effect of glucocorticoid hormones on
      neurogenesis in vitro via a two-pore domain potassium channel, TREK-1.
AB  - RATIONALE: Sustained stress and elevated glucocorticoid reduces neurogenesis,
      whereas chronic treatment with antidepressants increases neurogenesis and blocks
      the effects of stress. Recently, TREK-1, a two-pore domain (K(2)p) potassium
      channel, has been shown to be involved in the mechanisms of major depression.
      OBJECTIVES: This study aimed to investigate whether TREK-1 is involved in the
      alteration of neurogenesis according to glucocorticoids and antidepressants.
      RESULTS: The present study addressed the expression of TREK-1 in neural stem
      cells (NSCs) and found TREK-1 was only associated with NSC proliferation.
      Bupivacaine and curcumin, two strong TREK-1 channel inhibitors, significantly
      increased embryonic NSC viability and proliferation while transfection of hTREK-1
      decreased cell proliferation in embryonic NSCs. Dexamethasone, a glucocorticoid
      hormone receptor agonist, upregulated both protein and mRNA levels of TREK-1
      leading to decreased NSC proliferation which could be reversed by bupivacaine.
      Fluoxetine, a serotonin reuptake inhibitor antidepressant that has been
      previously found to inhibit TREK-1 channels, robustly, could attenuate the
      upregulation of TREK-1 expression and the inhibition of NSC proliferation induced
      by dexamethasone. CONCLUSIONS: Taken together, these data suggest that TREK-1 is
      associated with NSC proliferation and probably is a modulator of the effect that
      fluoxetine attenuates the inhibitory neurogenesis induced by glucocorticoid
      hormones.

PMID- 21069515
TI  - Ketamine self-administration in the rat: evidence for a critical role of setting.
AB  - RATIONALE: The abuse of ketamine has been reported to be on the rise over the
      past 15 years, but its abuse appears to be limited almost exclusively to the
      context of music and dance settings, indicating a major role of context in
      modulating its reinforcing effects. We have previously reported that amphetamine,
      cocaine, and heroin self-administration (SA) in the rat are differentially
      influenced by the setting in which testing takes place. The aim of the present
      study is to extend this pre-clinical model to ketamine. MATERIALS AND METHODS:
      Independent groups of rats with intravenous catheters were given the possibility
      to self-administer different doses of ketamine (125, 250, and 500 MUg/kg per
      infusion) under two environmental conditions. Some animals were housed in the SA
      chambers (resident rats) whereas other rats were transported to the SA chambers
      only for the test sessions (non-resident rats). After training, within-subject
      dose effect curves (125, 250, 500, and 1,000 MUg/kg per infusion) and break-point
      (during a progressive ratio session) were calculated. RESULTS: Non-resident rats
      readily acquired ketamine self-administration. In contrast, resident rats self
      administered only the highest dose of ketamine (500 MUg/kg), but still four times
      less than non-resident rats (11.0 +/- 6.0 vs 44.4 +/- 5.2 infusions during the
      last training session). No significant differences in break-point were found
      during the progressive ratio session. CONCLUSIONS: The present study confirms at
      a preclinical level the importance of setting for ketamine SA and further
      validates a previously described animal model of drug-environment interaction.

PMID- 21069517
TI  - An unusual case of allopurinol hypersensitivity syndrome potentiated by
      intravitreal bevacizumab.

PMID- 21069516
TI  - Phase advance with separate and combined melatonin and light treatment.
AB  - INTRODUCTION: Melatonin and light treatment are recommended for hastening
      adaptation to time zone change. We evaluated an afternoon regimen of 3 mg
      sustained release (SR) melatonin with and without next morning green light
      treatment for circadian phase advance. Effects of melatonin and light were tested
      separately and then combined to determine if the total phase change is additive
      or synergistic. MATERIAL AND METHODS: For each condition (melatonin, placebo,
      light, melatonin plus light), 11 subjects spent from Tuesday evening until Friday
      afternoon in the laboratory. For all four conditions, the following sleep
      schedule was maintained: night 1, 2345 to 0630 hours, night 2, 1600 to 0530
      hours, and night 3, 2345 to 0700 hours. For the light-only condition, light
      treatment was administered between 0700 and 0800 hours on Thursday. For melatonin
      only or placebo conditions, capsules were administered at 1600 hours on
      Wednesday. For the combined condition, melatonin was administered at 1600 hours
      on Wednesday with light treatment between 0600 and 0700 hours on Thursday.
      Circadian phase was assessed by calculating dim light melatonin onset (DLMO) from
      salivary melatonin, using a mean baseline +2 standard deviations (BL+2 SD)
      threshold. For all four conditions, pre-treatment and post-treatment DLMO
      assessments were on Tuesday and Thursday evenings, respectively. RESULTS: Phase
      advances were: melatonin at 1600 hours, 0.72 h p<0.005, light treatment from 0700
      to 0800 hours, 0.31 h, non-significant, and the combined treatment, 1.04 h
      p<0.0002. CONCLUSION: The phase advance from the combination of afternoon
      melatonin with next morning light is additive.

PMID- 21069518
TI  - A comparative analysis of the decongestive effect of oxymetazoline and
      xylometazoline in healthy subjects.
AB  - BACKGROUND: Oxymetazoline and xylometazoline are locally effective and direct
      acting drugs that relieve nasal congestion. The aim of this study was to
      objectively determine and compare the decongestive effects of oxymetazoline and
      xylometazoline in healthy subjects. METHODS: The study population comprised
      thirty healthy adults. All subjects underwent active anterior rhinomanometry
      (AARhm) and acoustic rhinometry (AR) tests following the application of
      oxymetazoline, xylometazoline, or placebo (physiological saline). The change in
      nasal resistance, nasal airflow, and different cross-sectional areas (CSAs) of
      the nasal cavity in the subjects were examined for each solution separately. The
      measurements were obtained over a 1-h period (baseline and 1, 15, 30, and 60 min
      post-dosing). All results were analyzed using the Kruskal-Wallis test and the
      Mann-Whitney U test. RESULTS: A total of 6,300 measurements of AARhm and AR were
      obtained. The application of placebo did not cause a statistically significant
      change in nasal resistance, nasal airflow, and CSAs (CSA1, 2, and 3,
      respectively) of the nasal cavity. In contrast, statistically significant changes
      in nasal resistance (inspiration p = 0.000 and p = 0.004; expiration p = 0.000
      and p = 0.000), nasal airflow (inspiration p = 0.000 and p = 0.004; expiration p
      = 0.000 and p = 0.000), and CSAs of the nasal cavity (CSA2 p = 0.000 and p =
      0.000, CSA3 p = 0.000 and p = 0.00), with the exception of CSA1 (p = 0.982 and p
      = 0.994), were obtained after the application of oxymetazoline and
      xylometazoline. A comparison of oxymetazoline and xylometazoline based on nasal
      resistance, nasal airflow, and CSAs of the nasal cavity demonstrated no
      statistically significant difference, except for CSA3. CONCLUSION: Oxymetazoline
      and xylometazoline are fast-acting and potent topical decongestants that have
      similar decongestive effects.

PMID- 21069519
TI  - Prescribed-drug utilization and polypharmacy in a general population in Greece:
      association with sociodemographic, health needs, health-services utilization, and
      lifestyle factors.
AB  - PURPOSE: Our aim was to analyze, in a multivariate framework, how
      sociodemographic, health-service utilization, health needs, and lifestyle risk
      factors influence drug utilization and polypharmacy (PP) in a general population
      in Greece. METHODS: The cross-sectional study took place in 2006. In total 1,005
      individuals (> 18 years old) of 1,388 who were approached (response rate 72.4%)
      were interviewed by trained interviewers. Thirty-seven reported only over-the
      counter (OTC) drug use and were excluded. The final sample was 968 individuals.
      Multivariable logistic regression and multinomial regression analyses were
      conducted to determine the predictors of drug use and PP at a significance level
      of p < 0.05. RESULTS: The results revealed a high rate of drug use and PP. Drug
      use and PP were more common among women and increased with age. Advanced age 65+
      [odds ratio (OR) 11.6), university education (OR 2.3), visits to physician (OR
      2.2), comorbidity (OR 6.8), or poor physical and mental health were associated
      with higher likelihood of using drugs. Minor (two to three drugs) and major (four
      or more drugs) PP depended on comorbidity, physical health, and increased age.
      Furthermore, visits to physicians (OR 1.1), smoking (OR 3.0), and obesity (OR
      3.8) increased the likelihood of major PP. CONCLUSIONS: Overall, drug utilization
      and PP depended on health needs followed by education, utilization of health
      services, and age. Social disparities do persist and, after adjustments for
      health needs and obesity, had a significant influence on PP.

PMID- 21069520
TI  - Erythropoetin as a novel agent with pleiotropic effects against acute lung
      injury.
AB  - Current pharmacotherapy for acute lung injury (ALI) and acute respiratory
      distress syndrome (ARDS) is not optimal, and the biological and physiological
      complexity of these severe lung injury syndromes requires consideration of
      combined-agent treatments or agents with pleiotropic action. In this regard,
      exogenous erythropoietin (EPO) represents a possible candidate since a number of
      preclinical studies have revealed beneficial effects of EPO administration in
      various experimental models of ALI. Taken together, this treatment strategy is
      not a single mediator approach, but it rather provides protection by modulating
      multiple levels of early signaling pathways involved in apoptosis, inflammation,
      and peroxidation, potentially restoring overall homeostasis. Furthermore, EPO
      appears to confer vascular protection by promoting angiogenesis. However, only
      preliminary studies exist and more experimental and clinical studies are
      necessary to clarify the efficacy and potentially cytoprotective mechanisms of
      EPO action. In addition to the attempts to optimize the dose and timing of EPO
      administration, it would be of great value to minimize any potential toxicity,
      which is essential for EPO to fulfill its role as a potential candidate for the
      treatment of ALI in routine clinical practice. The present article reviews recent
      advances that have elucidated biological and biochemical activities of EPO that
      may be potentially applicable for ALI/ARDS management.

PMID- 21069521
TI  - Pharmacists' views on integrated electronic prescribing systems: associations
      between usefulness, pharmacological safety, and barriers to technology use.
AB  - PURPOSE: Integrated electronic prescribing systems (IEPSs) are expected to
      improve efficiency and safety in the management of pharmaceuticals throughout the
      healthcare sector. In Sweden (population 9 million), more than 25 million e
      prescriptions each year are processed in the National IEPS. We set out to examine
      the introduction of an IEPS into pharmacists' practice with regard to impact on
      work efficiency and pharmacological safety. METHODS: A questionnaire was
      distributed to all pharmacists (n = 74) in a Swedish municipality (population
      145,000), where an IEPS had recently been introduced. The response rate was 70%.
      RESULTS: The IEPS was in general perceived to have expedited the processing of
      prescriptions and reduced the risk for prescription errors as well as the handing
      over of erroneous medications to patients. We found that there was a positive
      correlation between usefulness of the IEPS system for work efficacy and
      pharmacological safety, respectively (r =0 .524, p < .001) and a negative
      correlation between the usefulness of the IEPS for work efficacy and perception
      of barriers to technology use (r = -0.010, p > 0.05). We also found that there
      was a negative correlation between IEPS usefulness for pharmacological safety and
      that barriers to IEPS technology use were experienced (r = 0.031, p > 0.05).
      CONCLUSIONS: The results indicate that reduction of system unavailability due to
      technical issues will increase the perceived usefulness of IEPSs for pharmacists
      with regard to both work efficacy and pharmacological safety. We conclude that
      the introduction of an IEPS was well received by pharmacists; however, barriers
      to full acceptance remained, in particular, system unavailability due to
      technical problems.

PMID- 21069522
TI  - Pediatric pharmacogenetic and pharmacogenomic studies: the current state and
      future perspectives.
AB  - Genetic differences among individuals can explain some of the variability
      observed during drug treatment. Many studies have correlated the different
      pharmacological response to genetic variability, but most of them have been
      conducted on adult populations. Much less attention has been given to the
      pediatric population. Pediatric patients constitute a vulnerable group with
      regard to rational drug prescribing since they present differences arising from
      the various stages of development. However, only a few steps have been made in
      developmental pharmacogenomics. This review attempts to describe the current
      methods for pharmacogenetic and pharmacogenomic studies, providing some of the
      most studied examples in pediatric patients. It also gives an overview on the
      implication and importance of microRNA polymorphisms, transcriptomics,
      metabonomics, and proteomics in pharmacogenetics and pharmacogenomics studies.

PMID- 21069523
TI  - Evaluation of vertebral bone marrow fat content by chemical-shift MRI in
      osteoporosis.
AB  - OBJECTIVE: To quantitatively evaluate vertebral bone marrow fat content and
      investigate its association with osteoporosis with chemical-shift magnetic
      resonance imaging (CS-MRI). MATERIALS AND METHODS: Fifty-six female patients (age
      range 50-65 years) with varying bone mineral densities as documented with dual x
      ray absorptiometry (DXA) were prospectively included in the study. According to
      the DXA results, the patients were grouped as normal bone density, osteopenic, or
      osteoporotic. In order to calculate fat content, the lumbar region was visualized
      in the sagittal plane by CS-MRI sequence. "Region of interest" (ROI)s were placed
      within L3 vertebral bodies and air (our reference point) at different time points
      by different radiologists. Fat content was calculated through "signal intensity
      (SI) suppression rate" and "SI Index". The quantitative values were compared
      statistically with those obtained from DXA examinations. Kruskal-Wallis, and Mann
      Whitney U tests were used for comparisons between groups. The reliability of the
      measurements performed by two radiologists was evaluated with the "intraclass
      correlation coefficient". This study was approved by an institutional review
      board and all participants provided informed consent to participate in the study.
      RESULTS: Eighteen subjects with normal bone density (mean T score, 0.39 +/- 1.3
      [standard deviation]), 20 subjects with osteopenia (mean T score, -1.79 +/-
      0.38), and 18 subjects with osteoporosis (mean T score, -3 +/- 0.5) were
      determined according to DXA results. The median age was 55.9 (age range 50-64
      years) in the normal group, 55.5 (age range 50-64 years) in the osteopenic group,
      and 55.1 (age range 50-65 years) in the osteoporotic group (p = 0.872). In the CS
      MRI examination, the values of "SI suppression ratio" and "SI Index" (median
      [min:max]) were calculated by the first and second reader, independently. There
      was no statistically significant difference between the groups with regard to
      vertebral bone marrow fat content (p > 0.05). According to the "intraclass
      correlation coefficient", the measurements were reliable (0.55 and 0.60).
      CONCLUSIONS: Vertebral bone marrow fat content calculated with CS-MRI is not a
      reliable parameter for predicting bone mineral density in female patients aged
      between 50 and 65 years.

PMID- 21069524
TI  - Surgical treatment of syndesmotic diastasis: emphasis on effect of syndesmotic
      screw on ankle function.
AB  - Fifty-two consecutive adult patients with syndesmotic diastasis (SD) were treated
      with closed anatomical reduction and stable fixation by a trans-syndesmotic
      cancellous screw. A short leg splint was prescribed for a six week postoperative
      period. Treatment outcomes of syndesmotic screw removal at various time points
      were studied and compared (group 1 at six weeks, group 2 at three months and
      group 3 at an average of nine months). Recurrence of SD, incidence of syndesmotic
      screw breakage and ankle function were compared among the three groups.
      Recurrence of SD occurred in 15.8% (3/19) of patients in group 1, 15.0% (3/20) in
      group 2 and 0% (0/13) in group 3 (p = 0.054). Breakage of the syndesmotic screw
      occurred in three patients within three months (group 2, 15.0%) and in two
      patients beyond three months (group 3, each at six and 12 months, 15.4%). None of
      the group 1 patients experienced screw breakage (p = 0.034). Forty-three patients
      (82.7%) were classified as having satisfactory outcomes. Ankle function did not
      significantly differ among the three groups (p = 0.191), with or without
      syndesmotic screw breakage (p = 0.343) and with or without SD recurrence (p =
      0.218). In conclusion, restriction of daily activity for at least three months is
      required to prevent recurrence. Removal of the syndesmotic screw at six weeks may
      prevent its breakage but increases the risk of recurrence. Over an average follow
      up of 19 months, SD recurrence does not lead to deterioration in ankle function.

PMID- 21069525
TI  - New animal models of wear-particle osteolysis.
AB  - Particle debris resulting from in vivo degradation of total joint replacement
      components are recognised as the major factor limiting the longevity of joint
      reconstruction and the overall success of the procedure. Better understanding the
      complex cellular and tissue mechanisms and interactions resulting in wear
      particle osteolysis requires a number of experimental approaches, including
      radiological monitoring and analysis of retrieved tissues from clinical cases, in
      vitro experiments, and also animal-model investigations. In consideration of both
      their advantages and drawbacks, this paper provides an historical overview of
      numerous animal models that have been developed over the last three decades to
      investigate the pathogenesis of wear-particle osteolysis and to facilitate the
      preclinical testing of new treatment options. The authors also focus on recent
      studies in order to provide a better understanding of the current state of the
      art on this subject and propose some perspectives regarding technical and
      fundamental questions.

PMID- 21069526
TI  - The lateral condyle index: a new index for assessing the length of the lateral
      articular trochlea as predisposing factor for patellar instability.
AB  - The central trochlea has been considered as the major location of dysplasia. The
      purpose of this study was to investigate the influence of the lateral trochlea on
      patellar stability and to establish a new method for measuring the lateral
      trochlea on sagittal magnetic resonance (MR) images. Twenty-eight knees of 23
      patients suffering from lateral patellar subluxation (12 knees with radiological
      signs of central trochlear dysplasia) and of 46 patients without patellofemoral
      complaints (without central trochlear dysplasia) were analysed. The lateral
      condyle index was designed to measure the lateral trochlea by comparing the
      anterior cartilaginous trochlea (a) and the posterior aspect (p) [(a:p)* 100].
      The lateral condyle index showed high interrater reliability (r  = .94) and was
      significantly (p < 0.001) lower in symptomatic patients (86%) than in the control
      group (93%). These results show high clinical relevance of the lateral trochlea
      as another factor for patellar instability.

PMID- 21069527
TI  - Diagnosis and management of lymphoepithelial lesion of the parotid gland.
AB  - Patients with either benign or malignant parotid neoplasm are candidates for
      surgery, but patients with benign lymphoepithelial lesions of the parotid gland
      or Sjogren's syndrome do not necessarily require surgical treatment. However, the
      diagnosis of benign lymphoepithelial lesion of the parotid prior to surgery is
      challenging. In this case series, we retrospectively analyzed the records of 11
      patients presented between January 2006 and August 2007, with a solitary parotid
      mass diagnosed post-operatively as benign lymphoepithelial lesion or Sjogren's
      syndrome. Our analysis suggested that findings from physical examination and CT
      and MRI scans in the absence of neoplastic cells on fine needle aspiration biopsy
      could be used to make the diagnosis of lymphoepithelial lesion preoperatively. In
      a prospective study from September 2007 to June 2008, using the lessons learned
      from the analysis of the previous 11 patients, we were able to diagnose all 6
      cases of benign lymphoepithelial lesion or Sjogren's syndrome preoperatively.

PMID- 21069528
TI  - Intratendinous ganglion of the long head of the biceps tendon: US and MRI
      features (2010: 9b). Intratendinous ganglion.
AB  - We present a case report and literature review of the ultrasound (US) and
      magentic resonance imaging (MRI) features of an intratendinous ganglion
      originating from the long head of the biceps tendon. Intratendinous ganglia are
      very rare entities and intratendinous ganglion of the long head of the biceps
      tendon has only been described once. To the best of our knowledge, this is the
      first case report presenting the sonographic features of an intratendinous
      ganglion originating from the long head of the biceps tendon.

PMID- 21069532
TI  - Integration of Langerhans-like cells into a human skin equivalent.
AB  - Studies regarding cellular interactions between Langerhans cells and other skin
      cells are somehow hampered by the difficult cultivation of these cells in vitro.
      Here, we show that the human MUTZ-3 cell line can be differentiated into
      Langerhans-like cells in the presence of a cytokine cocktail including GM-CSF,
      TGF-beta1 and TNF-alpha. We used the expression of langerin, CD1a, CCR6 and the
      intracellular presence of Birbeck granules to identify the differentiated MUTZ-3
      cells (MUTZ-3-LCs). The aim of this study was to integrate MUTZ-3-LCs into a
      three-dimensional full-thickness skin model. On top of fibroblast-containing
      collagen matrix a mixture of primary human keratinocytes and MUTZ-3-LCs were
      seeded and cultured for 24 h. Subsequently, the models were lifted up to the air
      liquid interface. Histological evaluation featured a fully stratified epidermis
      with all characteristic epidermal strata. Langerin-positive cells were detected
      suprabasally within the epidermis indicating that keratinocytes provide
      environmental conditions for long-time maintenance of MUTZ-3-LCs. These skin
      models provide a tool to further investigate the interactions between Langerhans
      like cells and other skin cells and particularly learn more about the cutaneous
      immune response.

PMID- 21069531
TI  - EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy.
AB  - The M-band is the prominent cytoskeletal structure that cross-links the myosin
      and titin filaments in the middle of the sarcomere. To investigate M-band
      alterations in heart disease, we analyzed the expression of its main components,
      proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac
      function was assessed by echocardiography and compared to the expression pattern
      of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis.
      Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM)
      was accompanied by specific M-band alterations. The dominant splice isoform in
      the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart
      and correlated with a decrease in cardiac function (R = -0.86). In addition, we
      have analyzed the expressions of myomesins in human myocardial biopsies (N = 40)
      obtained from DCM patients, DCM patients supported by a left ventricular assist
      device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls.
      Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41
      fold (P < 0.001) in the DCM patients compared to control patients. In DCM hearts
      supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to
      controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a
      cell-specific manner, leading to a higher heterogeneity of the myocytes'
      cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH
      myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the
      dilated heart and might serve as a marker for DCM in mouse and human myocardium.

PMID- 21069533
TI  - Cell-dependent kinase inhibitor 2A and 2B genetic variability in patients with
      Alzheimer's disease.

PMID- 21069534
TI  - Small deep white matter lesions are associated with right-to-left shunts in
      migraineurs.
AB  - The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently
      observed in migraineurs and in patients with ischemic stroke. Previous studies
      have reported that the burden of WMLs did not increase with the intracardiac
      right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known
      to be associated with RLS in patients with stroke and dementia. The aim of the
      study was to demonstrate the difference in the size and location of WMLs,
      according to the existence of RLS in patients with headache. From the prospective
      headache registry, a total of 425 subjects (age, 30.8 +/- 5.1 years; 303 women;
      242 migraineurs; 183 patients with tension-type headache (TTH)) were
      retrospectively reviewed and evaluated for RLS and WMLs using M-mode power
      transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging
      scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the
      association between RLS presence and the location and size of WMLs. The number of
      small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic
      signals (MES) >= 11, were higher in patients with migraine (small dWMLs, 6.23 vs.
      4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no
      significant difference in the sum of periventricular WML grades or the total
      volume of dWMLs between TTH and migraine patients. Among the migraineurs, the
      patients with RLS more frequently had small dWMLs, aura, and heart disease
      compared to those without RLS. In addition, RLS were also independent predictors
      for the presence of small dWMLs from the multivariate binary regression analysis
      (p < 0.01; OR = 3.24; 95%CI 1.56-6.72). Small dWMLs are associated with RLS in
      young migraineurs. These results imply that paradoxical embolism may cause the
      small WMLs in some migraineurs.

PMID- 21069535
TI  - Implantable cardioverter defibrillator and 50-Hz electric and magnetic fields
      exposure in the workplace.
AB  - PURPOSE: The operation of implantable cardioverter defibrillators (ICD) can be
      disrupted by exposure to electromagnetic fields (EMF). In the workplace, some
      workers can be exposed to EMF higher than in daily life. We present an approach
      aimed at assessing fitness for work in this type of situation, based on in situ
      case studies in the absence of clinical and in vivo studies. METHODS: A risk
      assessment protocol was developed to measure the 50-Hz electric and magnetic
      fields in the various places where the worker is likely to be present. These
      measures are taken in the worker's presence, while monitoring the ICD operation.
      RESULTS: All cases of implanted ICD workers in EDF, the French electricity
      company (around 130,000 employees), and potentially exposed to high electric
      and/or magnetic fields, between 2004 and 2009 are presented. These three cases
      involved different work circumstances, with exposure to 50-Hz electric and/or
      magnetic fields. No interference of the ICD was observed. CONCLUSIONS: This
      information provides the basis for the occupational physician to make a decision
      about fitness for work. This procedure can be extended to other medical implants
      and to electromagnetic fields frequencies other than 50-Hz.

PMID- 21069536
TI  - Exposure to urban stressors and free testosterone plasma values.
AB  - OBJECTIVES: The chemical agents present in the environment, such as traffic
      pollutants, may affect male fertility. Traffic policemen are daily exposed to
      traffic pollutants. The aim of this study is to evaluate whether occupational
      exposure to urban stressors could cause alterations in free testosterone plasma
      values in male traffic policemen versus administrative staff of Municipal Police
      of a big Italian city. METHODS: Both groups were divided into two subgroups based
      on age (first group: 30-40 years; second group: 41-50 years) to assess whether
      age could affect laboratory results of free testosterone plasma levels in traffic
      policemen versus controls. The characterization of exposure to urban pollutants
      for traffic policemen was assessed using the concentrations of pollutants
      monitored in fixed stations. A total of 220 subjects were studied: 110 traffic
      policemen and 110 controls, after excluding subjects with main confounding
      factors. RESULTS: Mean free testosterone values were significantly lower in
      traffic policemen than in controls (P < 0.001). Such statistical reduction
      persisted stratifying the mean testosterone values for classes of age (30-40 and
      41-50 year) of workers (respectively P < 0.001 and P < 0.001). The distribution
      into classes of testosterone values in traffic policemen and in controls was
      significant (P < 0.001), and this result persisted after the stratification for
      classes of age of workers (30-40 year: P < 0.001) (41-50 year: P < 0.001).
      CONCLUSIONS: According to data in literature, free testosterone plasma levels
      could be used as an early biological marker, to be employed in occupational sets,
      valuable for the group, even before the onset of values out of range and of
      fertility disorders.

PMID- 21069537
TI  - The moderating effect of work-time influence on the effect of shift work: a
      prospective cohort study.
AB  - OBJECTIVES: To investigate whether work-time influence moderated the effect of
      shift work on psychological well-being measured as vitality, mental health,
      somatic stress symptoms, and disturbed sleep. METHODS: We used questionnaire data
      from 2,148 health care workers who finished their education in 2004 and were
      followed during their first 2 years of employment in the eldercare and health
      care sectors. We analyzed the effect of shift work, work-time influence, and the
      combination of these two variables adjusted for differences in baseline
      psychological well-being, background factors, and psychosocial work environment.
      RESULTS: Surprisingly, in this cohort, shift workers had higher vitality and
      better mental health than day workers. The combination of shift work and moderate
      or low work-time influence was associated with lower vitality, worse mental
      health, and more somatic stress symptoms than would have been expected when
      adding the separate effects of working hours and work-time influence. Work-time
      influence did not have any effect among day workers. CONCLUSION: Shift workers
      appear to be especially vulnerable to the negative effect of moderate or low work
      time influence.

PMID- 21069539
TI  - Secondary structure analysis of ITS2 in the rDNA of three Indian paramphistomid
      species found in local livestock.
AB  - Of paramphistomid trematodes, three species viz., Homalogaster paloniae,
      Calicophoron calicophorum and Orthocoelium streptocoelium are commonly prevalent
      in bovine hosts in Northeast India. The aim of the present study was to
      genetically characterise these species using rDNA second internal transcribed
      spacer (ITS2) so as to supplement the morphological criteria substantiated by
      molecular findings. The annotated ITS2 region from H. paloniae, C. calicophorum
      and O. streptocoelium were found to be 289 bp, 288 bp and 288 bp long,
      respectively. On comparison, the Indian isolates of the three species were
      observed to have a maximum identity of 99% with each of their respective
      counterparts from Japan. The secondary structure models were inferred using
      minimum free energy modelling algorithms. The paramphistomes displayed the
      typical four helix ITS2 secondary structure and differed from each other due to
      minor nucleotide differences. The consensus ITS2 secondary structure model
      revealed the presence of conservative motifs GACGAGGGUG and GCGGUAGAGUC in helix
      III. Monophyly is well supported for a clade consisting of the Japanese and
      Indian paramphistomes with significant bootstrap values.

PMID- 21069538
TI  - Developmental expression of COE across the Metazoa supports a conserved role in
      neuronal cell-type specification and mesodermal development.
AB  - The transcription factor COE (collier/olfactory-1/early B cell factor) is an
      unusual basic helix-loop-helix transcription factor as it lacks a basic domain
      and is maintained as a single copy gene in the genomes of all currently analysed
      non-vertebrate Metazoan genomes. Given the unique features of the COE gene, its
      proposed ancestral role in the specification of chemosensory neurons and the
      wealth of functional data from vertebrates and Drosophila, the evolutionary
      history of the COE gene can be readily investigated. We have examined the ways in
      which COE expression has diversified among the Metazoa by analysing its
      expression from representatives of four disparate invertebrate phyla: Ctenophora
      (Mnemiopsis leidyi); Mollusca (Haliotis asinina); Annelida (Capitella teleta and
      Chaetopterus) and Echinodermata (Strongylocentrotus purpuratus). In addition, we
      have studied COE function with knockdown experiments in S. purpuratus, which
      indicate that COE is likely to be involved in repressing serotonergic cell fate
      in the apical ganglion of dipleurula larvae. These analyses suggest that COE has
      played an important role in the evolution of ectodermally derived tissues (likely
      primarily nervous tissues) and mesodermally derived tissues. Our results provide
      a broad evolutionary foundation from which further studies aimed at the
      functional characterisation and evolution of COE can be investigated.

PMID- 21069540
TI  - Molecular evidence of Opisthorchis viverrini in infected bithyniid snails in the
      Lao People's Democratic Republic by specific hybridization probe-based real-time
      fluorescence resonance energy transfer PCR method.
AB  - Naturally occurring bithyniid snails, Bithynia siamensis goniomphalos
      (Prosobranchia: Bithyniidae), and their intermediate hosts were sampled from
      Khammouane Province, the Lao People's Democratic Republic, and the prevalence of
      the carcinogenic human liver fluke, Opisthorchis viverrini, was examined. The
      presence of O. viverrini cercariae in snails was examined by cercarial shedding
      test and then confirmed by specific hybridization probe-based real-time
      fluorescence resonance energy transfer (FRET) PCR method. The real-time FRET PCR
      method is based on a fluorescence melting curve analysis of a hybrid between an
      amplicon produced from the pOV-A6 specific sequence (Genbank accession no.
      S80278), a 162-bp repeated sequence specific to O. viverrini, and specific
      fluorophore-labeled probes. Mean melting temperature of O. viverrini DNA from the
      cercariae and each of two positive snails by shedding test was 66.3 +/- 0.1. The
      O. viverrini infection rate in snails was 2.47% (2/81) by cercarial shedding test
      but was 8.52% (4/47) by real-time FRET PCR method. The real-time FRET PCR method
      is rapid and effective in examining a large number of snail samples
      simultaneously. Validation using molecular evidence from this procedure provides
      another tool for surveying the prevalence of O. viverrini-infected snails in
      Southeast Asian countries.

PMID- 21069541
TI  - Video. Single-incision laparoscopic cholecystectomy.
AB  - BACKGROUND: Single-incision laparoscopic surgery (SILS) has been proposed as a
      minimally invasive technique with the advantages of smaller external scars and
      reduced pain. Furthermore, usage of the flexible endoscope for SILS in lieu of
      the standard laparoscope provides distinct visualization advantages. This video
      shows a single-incision cholecystectomy performed using a single incision placed
      through the umbilicus. METHODS: A 39-year-old woman with chronic symptomatic
      cholelithiasis was enrolled under institutional review board protocol to undergo
      SILS. She had previously undergone a laparoscopic tubal ligation. A single
      incision was made using the previous umbilical incision, and the abdomen was
      entered in an open fashion. The flexible endoscope was placed directly through
      the fascial incision, with two 5-mm ports on either side. Adhesions to the
      gallbladder were taken down with the harmonic scalpel. Dissection proceeded using
      an articulating grasper and retraction to identify the cystic duct and artery.
      The duct and artery were serially clipped and divided. The cystic duct was
      additionally secured with a loop ligature. The gallbladder was cauterized from
      the liver bed using the articulating hook cautery and extracted through the
      wound. RESULTS: The final incision placed at the base of the umbilicus was 7 mm
      long. The operative time was 58 min, with minimal blood loss recorded. The
      patient was discharged home on the day of the procedure and did not experience
      any postoperative complications. CONCLUSIONS: Single-incision cholecystectomy can
      be performed safely through one incision in the umbilicus, optimizing cosmesis.
      Substitution of the flexible endoscope for the standard laparoscope allows many
      greater degrees of visualization in SILS. This allows clear identification of the
      biliary ductal anatomy, allowing cholecystectomy to proceed safely. Placement of
      the endoscope directly through the incision decreases the profile of ports
      through the incision and increases maneuverability.

PMID- 21069542
TI  - Primary spinal hydatid cyst in a patient with acquired immunodeficiency syndrome.
AB  - Spinal hydatid cyst is a serious and unusual infectious disease. There is little
      information on infections caused by cestodes in patients with human
      immunodeficiency virus (HIV) infection. Although infrequent, infections by
      cestodes constitute a cause of disease in HIV-infected patients, especially in
      endemic areas. This report presents, for the first time in the literature,
      primary spinal cyst hydatid in a patient with acquired immunodeficiency syndrome.

PMID- 21069543
TI  - Study of the information delivery by general practitioners and rheumatologists to
      patients with acute low back pain.
AB  - Providing information to patients regarding appropriate management of LBP is a
      crucial component of primary care and treatment of low back pain (LBP). Limited
      knowledge is available, however, about the information delivered by physicians to
      patients with low back pain. Hence, this study aimed at evaluating (1) the self
      reported practices of French physicians concerning information about patients
      with acute LBP (2) the consistency of these practices with the COST B13
      guidelines, and (3) the effects of the delivery of a leaflet summarizing the COST
      B13 recommendations on the management of patient information, using the following
      study design: 528 French physicians [319 general practitioners (GP) and 209
      rheumatologists (RH)] were asked to provide demographic information, responses to
      a Fear Avoidance Beliefs questionnaire adapted for physicians and responses to a
      questionnaire investigating the consistency of their practice with the COST B13
      guidelines. Half of the participants (163 GP and 105 RH) were randomized to
      receive a summary of the COST B13 guidelines concerning information delivery to
      patient with low back pain and half (156 GP and 104 RH) were not given this
      information. The mean age of physicians was 52.1+/-7.6 years, 25.2% were females,
      75% work in private practice, 63.1% reported to treat 10-50 patients with LBP per
      month and 18.2%<10 per month. The majority of the physicians (71.0%) reported
      personal LBP episode (7.1% with a duration superior to 3 months). Among the 18.4%
      (97) of the physicians that knew the COST B13 guidelines, 85.6% (83/97) reported
      that they totally or partially applied these recommendations in their practice.
      The average work (0-24) and physical activity (0-24) FABQ scores were 21.2+/-8.4
      and 10.1+/-6.0, respectively. The consistency scores (11 questions scored 0 to 6,
      total score was standardized from 0 to 100) were significantly higher in the RH
      group (75.6+/-11.6) than in GP group (67.2+/-12.6; p<0.001). The delivery of a
      summary of the COST B13 guidelines significantly improved the consistency score
      (p=0.018). However, a multivariate analysis indicated that only GP consistency
      was improved by recommendations' delivery.The results indicated that GP were less
      consistent with the European COST B13 guidelines on the information of patients
      with acute LBP than RH. Interestingly, delivery of a summary of these guidelines
      to GP improved their consistency score, but not that of the RH. This suggests
      that GP information campaign can modify the message that they deliver to LBP, and
      subsequently could change patient's beliefs on LBP.

PMID- 21069544
TI  - Abnormalities of the lumbar spine in the coronal plane on plain abdominal
      radiographs.
AB  - The main objective of this study is to determine the prevalence of coronal
      abnormalities of the lumbar spine in a large population of patients with respect
      to their age and sex. Lumbar degenerative disease is associated with degenerative
      scoliosis. Degenerative scoliosis and lateral listhesis are important features to
      identify before decompressive surgery as deformity may not be seen on magnetic
      resonance imaging scans. Scoliosis and lateral listhesis may be important in the
      development of symptoms especially in an ageing population. All abdominal and
      plain kidney-ureter-bladder radiographs performed over a 10-month period were
      reviewed. 2,765 radiographs were assessed for scoliosis (Cobb angle greater then
      10 degrees ), lateral listhesis and evidence of osteoarthritis. The prevalence of
      scoliosis, lateral listhesis and osteoarthritis of the lumbar spine increased
      with age. Scoliosis and lateral listhesis were significantly more prevalent in
      women. Deformity starts to occur after the age of 50 and steadily increases with
      age. By the ninth decade nearly a quarter of patients have evidence of scoliosis
      and lateral listhesis. As the adult lumbar spine ages, the prevalence of lateral
      listhesis and degenerative scoliosis increases. It is important to appreciate
      these coronal abnormalities in patients undergoing decompressive surgery for
      spinal stenosis. This increase in deformity may have a greater impact as the
      population continues to age.

PMID- 21069545
TI  - Responsiveness of the 24-, 18- and 11-item versions of the Roland Morris
      Disability Questionnaire.
AB  - Several versions of the 24-item Roland Morris Disability Questionnaire (RMDQ)
      have been proposed; however, their responsiveness has not been extensively
      explored. The objective of this study was to compare the responsiveness of four
      versions of the RMDQ. Perceived disability was measured using the 24-item, two 18
      item and an 11-item RMDQ on 1,069 low back pain patients from six randomised
      controlled trials. Responsiveness was calculated using effect size, Guyatt's
      responsiveness index (GRI) and receiver operating characteristics (ROC) curves.
      Effect size analyses showed that both 18-item versions of the RMDQ were superior
      to the 24- and 11-item versions of the RMDQ. GRI showed that the 24- and 18-item
      versions of the RMDQ were similar but more responsive than the 11-item. ROC
      curves revealed that the 11-item was less responsive than the other three
      versions, which had similar responsiveness. The results of this study demonstrate
      that the 24-item and both 18-item versions of the RMDQ have similar
      responsiveness with all having superior responsiveness to the 11-item.

PMID- 21069546
TI  - Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss
      in mice.
AB  - Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the
      levels of bone-resorbing cytokines; however, the synergistic effects of these
      food ingredients have not been examined yet. This study was performed to
      elucidate the effect of concomitant intake of soy isoflavone and fish oil on bone
      mass in ovariectomized mice. Eight-week-old ddY female mice were subjected to
      ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil
      (So) as a control lipid source, isoflavone-supplemented safflower oil (So + I),
      fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil (Fo +
      I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX;
      however, this decrease was inhibited by the intake of isoflavone and/or fish oil.
      Histomorphometric analyses showed that bone volume and trabecular thickness in
      the distal femoral trabecular bone were significantly lower in the So group than
      in the sham group, but those were restored in the Fo + I groups. The number of
      osteoclasts was significantly decreased by isoflavone intake. The increased rate
      of bone resorption after OVX was inhibited by isoflavone and/or fish oil. The
      serum concentration of tumor necrosis factor alpha was increased after OVX, but
      was significantly lower with the combination of isoflavone with fish oil than
      isoflavone or fish oil alone. The results of this study indicated that the
      intakes of soy isoflavone and/or fish oil might have ameliorating effects on bone
      loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil
      at a low dose showed better effects on cytokines related with bone resorption.

PMID- 21069547
TI  - Severe osteomalacia caused by short bowel syndrome in a patient on long-term
      hemodialysis after parathyroidectomy.
AB  - In January 2009, a 70-year-old Japanese woman on long-term dialysis was admitted
      to our hospital for evaluation of a painful left leg. Maintenance dialysis was
      started in 1982, and parathyroidectomy was performed for secondary
      hyperparathyroidism in 2004. Most of her small intestine was resected because of
      superior mesenteric artery thrombosis in 2006, and the remaining small bowel only
      extended 50 cm distal to the ligament of Treitz. Parenteral nutrition was started
      after bowel resection. Fracture of her left leg occurred suddenly without any
      precipitating factors in January 2009, and iliac bone biopsy revealed severe
      osteomalacia with an increase of total osteoid volume (57.6%) (>15%) and no
      fibrous tissue (0%) (<0.5%). Although phosphorus and active vitamin D were
      administered intravenously to correct her hypophosphatemia and vitamin D
      deficiency, significant improvement was not achieved. This case indicates that
      when a patient on long-term dialysis with parathyroidectomy also suffers from
      short bowel syndrome, osteomalacia may become very severe. Lack of healing of the
      fracture, persistence of pain, and subsequent fracture even after vigorous
      treatment for low serum phosphate and calcitriol levels implied that these
      medications were not necessarily sufficient for this patient.

PMID- 21069548
TI  - Is reduced bone mineral density independently associated with coronary artery
      calcification in subjects older than 50 years?
AB  - It has not been clearly defined whether reduced bone mineral density (BMD) is a
      direct risk factor of vascular calcification. A total of 2,160 subjects who were
      older than 50 years and underwent routine health examination at the Seoul
      National University Hospital Healthcare System Gangnam Center were included in
      this study. Coronary artery calcium scores (CACS) were calculated to quantify the
      extent of coronary artery calcification (CAC) using computed tomography. Bone
      dual-energy X-ray absorptiometry was also performed in all the subjects. BMD was
      classified as normal, osteopenia, or osteoporosis according to the lowest T score
      in the lumbar spine, femoral neck, or total hip. The mean value of CACS was 66.1
      +/- 234.0, and 1,372 subjects (63.5%) showed no coronary artery calcium deposits.
      A gender difference in the association between BMD and CACS was observed; a
      significant relationship was identified only in women. Unadjusted odds ratio for
      the presence of CAC in female subjects with reduced BMD was 1.925 (95% CI 1.383
      2.679, p < 0.001). However, after adjusting for age and other risk factors, the
      association was no longer significant. Age, hypertension, glucose, and male
      gender were independent factors determining CAC in multiple regression analysis.
      Although reduced BMD and CAC were common findings among the elderly, the close
      association between them diminished after considering other factors affecting
      CAC.

PMID- 21069549
TI  - A versatile approach for modeling and simulating the tacticity of polymers.
AB  - We are introducing a versatile computerized approach to model and simulate
      polymer tacticities using seven single-stage statistical models. The theory
      behind the models, e.g., Bovey's versus Price's, Bernoullian, 1st or 2nd order
      Markovian, enantiomeric types, and combinations thereof is explained. One of the
      models, "E-B gen", which can be used to produce four types of enantiomorphically
      controlled tacticities, and the pentad distribution for the model "E-M1" are
      reported here for the first time. The relations of chain-end controlled models to
      binary copolymerizations are discussed in detail, and equations for the
      conversion of tacticity based probabilities to reactivity ratios to obtain
      related n-ad distributions are presented. The models were applied to 20 polymers
      with exemplary tacticities found in the literature. A related software program
      ("Polytact") based on Microsoft's Excel has been designed to calculate all
      relevant characteristics of the polymer tacticity and to present them in
      graphical form in a user-friendly manner. The program can be used to produce
      graphs of the triad, pentad and sequence length distributions and a simulation of
      50 monomer repeat units in the polymer for each of the seven models. One of the
      main intended uses of the program is to compare the computed n-ad distributions
      to those of experimental polymers obtained from NMR spectroscopy and to gain
      insight into the polymerization mechanisms.

PMID- 21069550
TI  - Metastasis of colorectal carcinoma to the testes: clinical presentation and
      possible pathways.
AB  - Distant metastasis from colorectal carcinoma most often occurs in the liver and
      lungs. Metastasis to bones, adrenals, lymph nodes, brain, and skin has also been
      reported. Metastatic colorectal carcinoma to the testes is very uncommon. Even
      more uncommon is testicular metastasis from rectal carcinoma. Researchers
      throughout the last few decades have not acquired a clear understanding of the
      lymphatic pathways involved in reported cases of testicular metastasis from
      primary colorectal carcinoma. These cases may present with testicular complaints
      after or even before the diagnosis of colorectal cancer; this is why it is
      crucial to differentiate between primary testicular tumor and a secondary one
      from a colorectal primary. We searched the English medical literature using the
      MEDLINE/PUBMED database from 1950 through January 2010. Our search yielded 33
      cases of testicular metastasis from rectal or colonic carcinoma. These cases are
      reviewed and summarized. This paper reviews the literature for all cases of
      testicular metastasis from colonic and rectal adenocarcinomas shedding light on
      the possible pathways of metastasis. We recommend that physicians be aware of the
      risk of metastasis from the colorectal region to the testis in their evaluation
      of patients with testicular symptoms in the setting of colorectal carcinoma.

PMID- 21069552
TI  - Evidence-based guidelines for treatment of uterine body neoplasm in Japan: Japan
      Society of Gynecologic Oncology (JSGO) 2009 edition.
AB  - Endometrial carcinoma is one of the most common gynecologic malignancies in Japan
      and its incidence has increased recently. Although surgery is the cornerstone of
      the management of patients with endometrial cancer, there is significant
      variation in Japan with regard to the type of hysterectomy employed.
      Additionally, it remains controversial whether full nodal staging is required in
      all patients. Furthermore, adjuvant therapy differs between Japan and Western
      countries. To delineate clearly the standard of care for endometrial cancer
      treatment in Japan, the guidelines for the treatment of endometrial cancer were
      published in 2006 and revised in 2009. The 2009 edition included topics not
      addressed in the previous edition including the treatment of mesenchymal tumors,
      for example leiomyosarcoma, and sections covering the treatment of serous and
      clear-cell adenocarcinoma. These guidelines are composed of nine chapters and
      include nine algorithms. The guidelines also contain fifty-one clinical questions
      (CQs) and each CQ consists of recommendations, background, explanations, and
      references. The treatment recommendations herein are tailored to reflect current
      Japanese clinical practice and ensure equitable care for all Japanese women
      diagnosed with endometrial cancer.

PMID- 21069551
TI  - Anorectal melanoma with a KIT-activating mutation, which is a target for tyrosine
      kinase inhibitor.
AB  - Recent advances in our understanding of the genetic mutations associated with
      melanoma have led to the classification of distinct melanoma subtypes. A number
      of reports have consistently demonstrated that mucosal and acral melanomas more
      commonly harbor KIT-activating mutations than do other subtypes. Success in
      treating gastrointestinal stromal tumors with imatinib has led to speculation
      that KIT-mutated melanoma might also be effectively managed using this approach.
      A 78-year-old woman presented with a 4-month history of rectal bleeding. A
      colonoscopy revealed a black polypoid mass, 30 mm in diameter, originating near
      the dentate line, and a biopsy revealed malignant melanoma. Computed tomography
      showed multiple liver and lung metastases. A KIT mutation analysis showed the
      L576P mutation in exon 11. The patient did not want to undergo chemotherapy
      including a tyrosine-kinase inhibitor, so palliative radiotherapy for rectal
      symptoms was performed, but the patient died 4 months later due to disease
      progression. We describe the first case of anorectal melanoma with a KIT
      activating mutation in Japan and summarize findings from the literature regarding
      the efficacy of KIT kinase inhibitors on this melanoma subtype.

PMID- 21069553
TI  - Physical origin of shear-banding in jammed systems.
AB  - Jammed systems all have a yield stress. Among these materials some have been
      shown to shear-band but it is as yet unclear why some materials develop shear
      band and some others do not. In order to rationalize existing data concerning the
      flow characteristics of jammed systems and in particular understand the physical
      origin of such a difference, we propose a simple approach for describing the
      steady flow behaviour of yield stress fluids, which retains only basic physical
      ingredients. Within this framework we show that in the liquid regime the
      behaviour of jammed systems turns from that of a simple yield stress fluid
      (exhibiting homogeneous flows) to a shear-banding material when the ratio of a
      characteristic relaxation time of the system to a restructuring time becomes
      smaller than 1, thus suggesting a possible physical origin of these trends.

PMID- 21069554
TI  - Cooperative translocation dynamics of biopolymer chains through nanopores in a
      membrane: Slow dynamics limit.
AB  - The cooperative translocation dynamics of two complementary single-stranded DNA
      chains through two nanopores located in a membrane is investigated theoretically.
      The translocation process is considered to be quasi-equilibrium, and then under
      the limit of slow dynamics the average translocation times are numerically
      presented under different conditions. It is shown that the effects of the
      chemical potential gradient, the recombination energy and the distance between
      the two nanopores on the cooperative translocation are significant. The present
      model predicts that the cooperative translocation of such two chains can shorten
      the translocation time, reduce the backward motion and thus improve the
      translocation efficiency.

PMID- 21069555
TI  - Biotechnological process for obtaining new fermented products from cashew apple
      fruit by Saccharomyces cerevisiae strains.
AB  - In Brazil, the use of cashew apple (Anacardium occidentale L.) to obtain new
      products by biotechnological process represents an important alternative to avoid
      wastage of a large quantity of this fruit, which reaches about 85% of the annual
      production of 1 million tons. This work focuses on the development of an
      alcoholic product obtained by the fermentation of cashew apple juice. The
      inoculation with two different strains of yeast Saccharomyces cerevisiae viz. SCP
      and SCT, were standardized to a concentration of 10(7 )cells ml(-1). Each
      inoculum was added to 1,500 ml of cashew must. Fermentation was performed at 28
      +/- 3 degrees C and aliquots were withdrawn every 24 h to monitor soluble sugar
      concentrations, pH, and dry matter contents. The volatile compounds in fermented
      products were analyzed using the gas chromatography/mass spectrometry (GC/MS)
      system. After 6 days, the fermentation process was completed, cells removed by
      filtration and centrifugation, and the products were stabilized under
      refrigeration for a period of 20 days. The stabilized products were stored in
      glass bottles and pasteurized at 60 +/- 5 degrees C/30 min. Both fermented
      products contained ethanol concentration above 6% (v v(-1)) while methanol was
      not detected and total acidity was below 90 mEq l(-1), representing a pH of 3.8
      3.9. The volatile compounds were characterized by the presence of aldehyde (butyl
      aldehyde diethyl acetal, 2,4-dimethyl-hepta-2,4-dienal, and 2-methyl-2-pentenal)
      and ester (ethyl alpha-methylbutyrate) representing fruity aroma. The strain SCT
      was found to be better and efficient and this produced 10% more alcohol over that
      of strain SCP.

PMID- 21069556
TI  - Pharmacophore-driven identification of PPARgamma agonists from natural sources.
AB  - In a search for more effective and safe anti-diabetic compounds, we developed a
      pharmacophore model based on partial agonists of PPARgamma. The model was used
      for the virtual screening of the Chinese Natural Product Database (CNPD), a
      library of plant-derived natural products primarily used in folk medicine. From
      the resulting hits, we selected methyl oleanonate, a compound found, among
      others, in Pistacia lentiscus var. Chia oleoresin (Chios mastic gum). The acid of
      methyl oleanonate, oleanonic acid, was identified as a PPARgamma agonist through
      bioassay-guided chromatographic fractionations of Chios mastic gum fractions,
      whereas some other sub-fractions exhibited also biological activity towards
      PPARgamma. The results from the present work are two-fold: on the one hand we
      demonstrate that the pharmacophore model we developed is able to select novel
      ligand scaffolds that act as PPARgamma agonists; while at the same time it
      manifests that natural products are highly relevant for use in virtual screening
      based drug discovery.

PMID- 21069557
TI  - Molecular assessment of microbiota structure and dynamics along mixed olive oil
      and winery wastewaters biotreatment.
AB  - The major parcel of the degradation occurring along wastewater biotreatments is
      performed either by the native microbiota or by added microbial inocula. The main
      aim of this study was to apply two fingerprinting methods, temperature gradient
      gel electrophoresis (TGGE) and length heterogeneity-PCR (LH-PCR) analysis of 16S
      rRNA gene fragments, in order to assess the microbiota structure and dynamics
      during mixed olive oil and winery wastewaters aerobic biotreatment performed in a
      jet-loop reactor (JLR). Sequence homology analysis showed the presence of
      bacterial genera Gluconacetobacter, Klebsiella, Lactobacillus, Novosphingobium,
      Pseudomonas, Prevotella, Ralstonia, Sphingobium and Sphingomonas affiliated with
      five main phylogenetic groups: alpha-, beta- and gamma-Proteobacteria, Firmicutes
      and Bacteroidetes. LH-PCR analysis distinguished eight predominant DNA fragments
      correlated with the samples showing highest performance (COD removal rates of 67
      up to 75%). Cluster analysis of both TGGE and LH-PCR fingerprinting profiles
      established five main clusters, with similarity coefficients higher than 79%
      (TGGE) and 62% (LH-PCR), and related with hydraulic retention time, indicating
      that this was the main factor responsible for the shifts in the microbiota
      structure. Canonical correspondence analysis revealed that changes observed on
      temperature and O(2) level were also responsible for shifts in microbiota
      composition. Community level metabolic profile analysis was used to test
      metabolic activities in samples. Integrated data revealed that the microbiota
      structure corresponds to bacterial groups with high degradative potential and
      good suitability for this type of effluents biotreatments.

PMID- 21069558
TI  - Scaffolds with a standardized macro-architecture fabricated from several calcium
      phosphate ceramics using an indirect rapid prototyping technique.
AB  - Calcium phosphate ceramics, commonly applied as bone graft substitutes, are a
      natural choice of scaffolding material for bone tissue engineering. Evidence
      shows that the chemical composition, macroporosity and microporosity of these
      ceramics influences their behavior as bone graft substitutes and bone tissue
      engineering scaffolds but little has been done to optimize these parameters. One
      method of optimization is to place focus on a particular parameter by normalizing
      the influence, as much as possible, of confounding parameters. This is difficult
      to accomplish with traditional fabrication techniques. In this study we describe
      a design based rapid prototyping method of manufacturing scaffolds with virtually
      identical macroporous architectures from different calcium phosphate ceramic
      compositions. Beta-tricalcium phosphate, hydroxyapatite (at two sintering
      temperatures) and biphasic calcium phosphate scaffolds were manufactured. The
      macro- and micro-architectures of the scaffolds were characterized as well as the
      influence of the manufacturing method on the chemistries of the calcium phosphate
      compositions. The structural characteristics of the resulting scaffolds were
      remarkably similar. The manufacturing process had little influence on the
      composition of the materials except for the consistent but small addition of, or
      increase in, a beta-tricalcium phosphate phase. Among other applications,
      scaffolds produced by the method described provide a means of examining the
      influence of different calcium phosphate compositions while confidently excluding
      the influence of the macroporous structure of the scaffolds.

PMID- 21069559
TI  - Covalent attachment of a bioactive hyperbranched polymeric layer to titanium
      surface for the biomimetic growth of calcium phosphates.
AB  - This work is investigating the chemical grafting on Ti surface of a
      polymer/calcium phosphate coating of improved adhesion for enhanced bioactivity.
      For this purpose, a whole new methodology was developed based on covalently
      attaching a hyperbranched poly(ethylene imine) layer on Ti surface able to
      promote calcium phosphate formation in a next deposition stage. This was achieved
      through an intermediate surface silanization step. The research included
      optimization both of the reaction conditions for covalently grafting the
      intermediate organosilicon and the subsequent hyperbranched poly(ethylene imine)
      layers, as well as of the conditions for the mechanical and chemical pretreatment
      of Ti surface before coating. The reaction steps were monitored employing FTIR
      and XPS analyses, whereas the surface morphology and structure of the successive
      coating layers were studied by SEM combined with EDS. The analysis confirmed the
      successful grafting of the hybrid layer which demonstrated very good ability for
      hydroxyapatite growth in simulated body fluid.

PMID- 21069561
TI  - Founding figures of pharmacokinetics: tribute to Malcolm Rowland.

PMID- 21069560
TI  - Enhanced osteogenic differentiation of cord blood-derived unrestricted somatic
      stem cells on electrospun nanofibers.
AB  - A new stem cell-scaffold construct based on poly-L-lactide (PLLA) nanofibers
      grafted with collagen (PLLA-COL) and cord blood-derived unrestricted somatic stem
      cells (USSC) were proposed to hold promising characteristics for bone tissue
      engineering. Fabricated nanofibers were characterized using SEM, ATR-FTIR,
      tensile and contact angle measurements. The capacity of PLLA, plasma-treated PLLA
      (PLLA-pl) and PLLA-COL scaffolds to support proliferation and osteogenic
      differentiation of USSC was evaluated using MTT assay and common osteogenic
      markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition
      and bone-related genes. All three scaffolds showed nanofibrous and porous
      structure with suitable physical characteristics. Higher proliferation and
      viability of USSC was observed on PLLA-COL nanofibers compared to control
      surfaces. In osteogenic medium, ALP activity and calcium deposition exhibited the
      highest values on PLLA-COL scaffolds on days 7 and 14. These markers were also
      greater on PLLA and PLLA-pl compared to TCPS. Higher levels of collagen I,
      osteonectin and bone morphogenetic protein-2 were detected on PLLA-COL compared
      to PLLA and PLLA-pl. Runx2 and osteocalcin were also expressed continuously on
      all scaffolds during induction. These observations suggested the enhanced
      proliferation and osteogenic differentiation of USSC on PLLA-COL nanofiber
      scaffolds and introduced a new combination of stem cell-scaffold constructs with
      desired characteristics for application in bone tissue engineering.

PMID- 21069562
TI  - Adolescent sexual activity and the development of delinquent behavior: the role
      of relationship context.
AB  - Despite the well-established association between adolescent sexual activity and
      delinquent behavior, little research has examined the potential importance of
      relationship contexts in moderating this association. The current study used
      longitudinal, behavioral genetic data on 519 same-sex twin pairs (48.6% female)
      divided into two age cohorts (13-15 and 16-18 years olds) drawn from the National
      Longitudinal Study of Adolescent Health. Analyses tested whether adolescent
      sexual activity that occurred in romantic versus non-romantic relationships was
      associated with delinquency from adolescence to early adulthood, after
      controlling for genetic influences. Results indicated that, for both younger and
      older adolescents, common underlying genes influence both sexual behavior and
      delinquency. After controlling for these genetic influences, there was no within
      twin pair association between sexual activity and delinquency in younger
      adolescents. In older adolescents, sexual activity that occurred in romantic
      relationships predicted lower levels of delinquency, both cross-sectionally and
      longitudinally, whereas sexual activity in non-romantic relationships predicted
      higher levels of delinquency. These results are consistent with emerging research
      that suggests that the psychological correlates of adolescent sexual activity may
      be moderated by the social context in which this activity occurs.

PMID- 21069563
TI  - Cytotoxic effects of two organotin compounds and their mode of inflicting cell
      death on four mammalian cancer cells.
AB  - In this report, we have tested the cytotoxicity of two organotin (OT) compounds
      by flow cytometry on a panel of immortalized cancer cell lines of human and
      murine origin. Although the OT compounds exhibited varying levels of
      cytotoxicity, diphenylmethyltin chloride was more toxic than 1,4-bis
      (diphenylchlorostannyl)p-xylene on all cell lines tested. The OT compounds were
      found to be highly cytotoxic to lymphoma cell lines with lower toxicity toward
      the HeLa cervical cancer cell line. In order to discern the mechanism by which
      cell death was induced, additional experiments were conducted to monitor
      characteristic changes consistent with apoptosis and/or necrosis. Cell lines
      treated with the experimental compounds indicated that there was no consistent
      mode of cell death induction. However, both compounds induced apoptosis in the
      pro-B lymphocyte cell line, NFS-70. The work presented here also demonstrates
      that the two OT compounds possess selective cytotoxicity against distinct
      transformed cell lines.

PMID- 21069564
TI  - A liberation psychology approach to acculturative integration of migrant
      populations.
AB  - This paper describes an acculturative integration approach that stresses the
      contribution of liberation psychology. Immigrant integration is a challenge for
      receiving countries in the Western world due to the frequent asymmetrical and
      oppressive conditions suffered by newcomers in their new settlements. The cross
      cultural perspective connects integration with psychological acculturation,
      emphasizing harmony between acquisitions of the new culture while maintaining
      cultural heritage, and creating opportunities for intergroup relationships. In
      turn, liberation psychology permits an understanding of the acculturative
      transition as an empowerment and self-construction process by which immigrants
      acquire a new vision of the world and of themselves, transforming both structural
      conditions and themselves. From this perspective we conceptualize acculturative
      integration as the process by which newcomers become an accepted part of the new
      society through a reflexive and evaluative process, changing their social
      references and position, rebuilding their social and personal resources, and
      achieving a new agency in coherence with their new challenges and goals. In this
      process, they acquire critical thinking about unequal conditions, gain capacities
      to respond to the inequalities, and take effective actions to confront them. We
      illustrate this process using the narratives of nine Moroccan women who are
      living in asymmetrical and oppressive local contexts in Andalusia, the southern
      most region of Spain.

PMID- 21069565
TI  - Culture and community psychology: toward a renewed and reimagined vision.
AB  - Interest is growing in community psychology to look more closely at culture.
      Culture has resided in community psychology in its emphasis on context, ecology,
      and diversity, however we believe that the field will benefit from a more
      explicit focus on culture. We suggest a cultural approach that values the
      community's points of view and an understanding of shared and divergent meanings,
      goals, and norms within a theory of empowerment. Furthermore, we posit the
      importance of pluralistic, multi-method programs of research and action
      encompassing both idiographic and nomothetic approaches, and critical reflexivity
      of our roles and agendas. Culture can be further incorporated into all the
      branches and fibers of community psychology.

PMID- 21069566
TI  - Distribution of nonprescription pharmaceuticals in central Indiana streams and
      effects on sediment microbial activity.
AB  - Since the discovery of trace concentrations of pharmaceuticals in streams and
      treated drinking water around the world, a call has been made by both the
      scientific community and the general public to increase understanding of the
      potential effects these compounds may have on freshwater integrity. We measured
      abundance and distribution of pharmaceuticals in headwater streams across the
      Upper White River Watershed of central Indiana. Four nonprescription
      pharmaceuticals (1,7-dimethylxanthine, caffeine metabolite; acetaminophen;
      caffeine; cotinine, nicotine metabolite) were found at one or more sites with
      mean concentrations of 0.038, 0.109, 0.057 and 0.041 MUg/l, respectively.
      Caffeine was measured at trace concentrations at all sites sampled. Higher
      pharmaceutical concentrations were associated with streams having >90%
      agricultural land use in the sub watershed, suggesting that nonpoint sources,
      such as septic tanks, may contribute to stream pharmaceutical contamination. To
      assess the influence of these pharmaceuticals on stream microbial activity, we
      measured changes in sediment respiration and nutrient uptake in response to
      pharmaceuticals using both in vitro and in situ techniques. For in vitro
      experiments, respiration rates were not significantly different from controls
      with pharmaceutical exposure. However, net NO(3) (-)-N uptake increased
      significantly with nicotine concentrations. Net NH(4)(+)-N uptake was reduced in
      response to caffeine and nicotine exposure. In situ experiments indicated
      nicotine exposure increased microbial respiration. Our data show pharmaceuticals
      are ubiquitous in headwater streams of central Indiana and likely influence
      stream microbial activity depending on the pharmaceutical compound and history of
      exposure.

PMID- 21069567
TI  - Bone morphogenic protein-7 serum level decreases significantly in patients with
      contrast-induced nephropathy.
AB  - BACKGROUND AND AIM: Previous studies have demonstrated that endogenous bone
      morphogenic protein-7 (BMP-7) level is reduced in acute kidney injury and
      administration of exogenous BMP-7 has a beneficial effect on kidney function. In
      spite of preventive management, contrast-induced nephropathy (CIN) is still the
      third cause of acute deterioration of kidney function in hospitalized patients.
      With this background in mind, we studied changes in serum BMP-7 in a group of
      patients with chronic kidney disease and contrast-induced nephropathy. MATERIALS
      AND METHODS: We enrolled 45 consecutive adult patients with a baseline serum
      creatinine >= 1.4 mg/dl admitted for coronary angiography. We measured serum BMP
      7 levels before and 48 h after coronary angiography. The primary end point was
      the development of CIN, defined as an increase in serum creatinine concentration
      by 0.25 mg/dl or 25% over the baseline value within 72 h from contrast exposure.
      RESULTS: Overall, CIN occurred in 8 (17%) patients. The concentrations of serum
      BMP-7 were significantly decreased in the CIN group compared to baseline (488.6
      +/- 56.8 vs. 356.4 +/- 24.8, P = 0.01); in contrast, the concentration of BMP-7
      level did not change in patients without CIN (444.6 +/- 54.6 vs. 440.0 +/- 53.9,
      P = 0.09). CONCLUSION: BMP-7 level significantly decreases in patients who
      develop CIN after coronary angiography. Therefore, BMP-7 might be a diagnostic
      biomarker for CIN and a possibly promising agent for the treatment of CIN.

PMID- 21069568
TI  - Outcome study of upper pole heminephroureterectomy in children.
AB  - OBJECTIVE: We assessed the role and long-term outcome of upper pole
      heminephroureterectomy in the treatments of non-functioning upper renal moieties
      in children with duplex kidneys. METHODS: In a period of 10 years, forty-three
      patients (male: female ratio 6:37) underwent upper pole heminephroureterectomy; a
      total of 25 patients were diagnosed prenatally. Imaging modalities included renal
      and bladder ultrasound in all 43 patients, static 99 m technetium
      dimercaptosuccinic acid (DMSA) in 21 patients, micturating cystourethrogram in 28
      patients, MAG-3 in 13, cystoscopy in 30, IVU in 31 and DTPA, retrograde
      pyelography, antegrade pyelography in 1 patient. The main presentation was with
      urinary tract infections. Operation was performed through a combination of
      anterolateral loin incision plus right or left inguinal incision in 34 patients
      and high flank incision in 9 patients, for various abnormalities. One patient
      underwent also initial puncture of a ureterocele. RESULTS: Five patients (12%)
      had immediate post-operative complications. Thirteen patients (30%) had late post
      operative complications. Long-term follow-up revealed no complication in 35 (81%)
      patients and one (2%) patient had one episode of UTI and intermittent abdominal
      pain. Three patients (7%) had long-term incontinence. Four patients (9%) had a
      second procedure performed. CONCLUSION: Based on our experience, it seems that
      upper pole heminephroureterectomy is the treatment of choice in cases of
      obstructed upper segments of duplicated kidneys, when the affected segment
      contributes to less than 10% of the overall renal function.

PMID- 21069569
TI  - Interstitial nephritis and autoimmune pancreatitis: a case report.
AB  - Autoimmune pancreatitis is a rare form of pancreatitis characterized by
      responsiveness to steroid therapy and an often relapsing disease course. The
      mainstay of therapy is oral corticotherapy. Associations of interstitial
      nephritis with various autoimmune disorders have been described. We hereby report
      the case of a 69-year-old Caucasian man with a 2-year history of autoimmune
      pancreatitis, who presented with impairment of kidney function, proteinuria, and
      hypertension. Renal histopathology showed severe diffuse interstitial nephritis.
      With oral prednisone and ACE inhibitor therapy, complete recovery of kidney
      function was not achieved and proteinuria persisted. Therefore, mycophenolate
      mofetil was initiated. After 8 weeks, serum creatinine decreased, and a nearly
      complete and sustained resolution of proteinuria was seen, while tapering oral
      steroid doses. With autoreactive T cells playing a major role in the pathogenesis
      of both diseases, a common etiology of pancreatitis and interstitial nephritis
      can be assumed, and the beneficial effects of an inhibitor of lymphocyte
      proliferation, such as mycophenolate mofetil, can be explained. We infer from our
      case that mycophenolate mofetil can be effective in the control of simultaneous
      autoimmune pancreatitis and interstitial nephritis.

PMID- 21069570
TI  - Clinical usefulness of lanthanum carbonate for serum phosphate control in
      difficult patients.
AB  - BACKGROUND: The adequate control of phosphataemia is of major importance in end
      stage renal disease patients on maintenance dialysis. Recently, lanthanum
      carbonate (LC) has been added to the phosphate binder armamentarium. To our
      knowledge, no studies have yet evaluated the usefulness of this drug in
      uncontrolled hyperphosphataemic patients. METHODS: This was a 6-month prospective
      observational study. Patients on chronic hemodialysis who had previously failed
      to achieve serum phosphate control were enrolled. Thirty-four patients (i.e. 11%
      out of 305 from three dialysis units) met the inclusion criteria. Lanthanum
      carbonate was introduced and titrated to achieve serum phosphate control,
      according to the KDOQI guidelines. Clinical targets, gastrointestinal symptoms,
      and patients' satisfaction with therapy were assessed at baseline and after 6
      months. RESULTS: Eight patients (23.5%) were withdrawn from the study due to side
      effects. In the remaining patients, serum phosphate level significantly decreased
      from 5.8 to 4.4 mg/dl and calcium-phosphate product also decreased significantly
      from 55.6 to 41.8 mg(2)/dl(2). The average number of all phosphate binder tablets
      taken per day was reduced from 6.7 to 4.7. Evaluation scores of dyspeptic
      symptoms and of patient's satisfaction with therapy also improved: from 7.5 to
      5.3 and from 6.6 to 8.1, respectively. CONCLUSIONS: The introduction of LC
      improved serum phosphate control in over 70% of these "difficult patients". A
      lower pill burden was also obtained, which might help to simplify treatment and
      increase patients' compliance. Dyspeptic symptoms and overall satisfaction with
      treatment also improved.

PMID- 21069571
TI  - Optimization of cell-based assays to quantify the anti-inflammatory/allergic
      potential of test substances in 96-well format.
AB  - OBJECTIVE: There is an insistent need for robust, reliable, and optimized assays
      for screening novel drugs targeting the inflammatory/allergic markers. The
      present study describes about the optimization of eight cell-based assays
      utilizing mammalian cell lines in 96-well format for quantifying anti
      inflammatory/allergic drug candidates. MATERIALS AND METHODS: We estimated the
      inhibitory response of reference compounds: 1400 W dihydrochloride on LPS-induced
      NO release, celecoxib on LPS-induced PGE(2) production and dexamethasone on LPS
      induced pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha production by
      J774A.1 murine macrophages. Response of acetylsalicylic acid and celecoxib was
      studied on A23187-induced TXB(2) production; captopril on A23187-stimulated
      LTB(4) production by HL-60 cells. Effect of ketotifen fumarate was evaluated on
      A23187-elicited histamine release by RBL-2H3 cells. Each experiment was repeated
      twice to assess the reproducibility and suitability of the assays by determining
      appropriate statistical tools viz. %CV, S/B and Z' factor. RESULTS: 1400 W
      dihydrochloride was capable of inhibiting LPS-induced NO levels (IC(50) = 10.7
      MUM). Dexamethasone attenuated LPS-induced IL-1 beta (IC(50) = 70 nM), IL-6
      (IC(50) = 58 nM) and TNF-alpha (IC(50) = 44 nM) release, whereas celecoxib, a
      specific COX-2 inhibitor showed marked reduction in LPS-induced PGE(2) (IC(50) =
      23 nM) production. Captopril (IC(50) = 48 MUM) and ketotifen fumarate (IC(50) =
      36.4 MUM) demonstrated potent inhibitory effect against A23187-stimulated LTB(4)
      and histamine levels, respectively. Both acetylsalicylic acid (IC(50) = 5.5 MUM)
      and celecoxib (IC(50) = 7.9 nM) exhibited concentration-dependent decrease in
      TXB(2) production. Results for all the cell assays from two experiments showed a
      Z' factor varying from 0.30 to 0.99; the S/B ratio ranged from 2.39 to 24.92; %CV
      ranged between 1.52 and 20.14. CONCLUSION: The results proclaim that these cell
      based assays can act as ideal tools for screening new anti-inflammatory/anti
      allergic compounds.

PMID- 21069572
TI  - Atorvastatin exhibits anti-inflammatory and anti-oxidant properties in adjuvant
      induced monoarthritis.
AB  - Arthritis is a joint disorder where the joint damage is associated with elevated
      levels of inflammatory mediators and reactive oxygen species (ROS). The
      inflammatory hyperalgesia associated with arthritis has been shown to be
      attenuated by anti-hyperlipidemic drug, atorvastatin. The present study was
      carried out to evaluate the effect of atorvastatin on joint inflammation and
      associated oxidative stress markers in a rat model where arthritis was induced by
      intra-articular injection of 0.1 ml of 0.1% Freund's Complete Adjuvant (FCA).
      Atorvastatin (10 mg and 50 mg/kg) and diclofenac (5 mg/kg) were administered
      orally, daily during the study period of 4 days and their effect on joint
      inflammation was evaluated by measuring joint diameter, levels of glutathione
      (GSH), thiobarbituric acid reactive substances (TBARS), activity of super oxide
      dismutase (SOD) and tissue histology. Atorvastatin produced a dose-dependent
      reduction in joint inflammation that was associated with normalization of levels
      of oxidative stress markers and tissue histology and its effect was found to be
      comparable to that of diclofenac.

PMID- 21069573
TI  - Energy budget in Daphnia magna exposed to natural stressors.
AB  - BACKGROUND, AIM, AND SCOPE: Climate changes are nowadays an important issue of
      concern, and it is expected that in the near future it will be intensified,
      leading to extreme environmental conditions. These changes are expected to
      originate additional sources of stress; therefore, the exposure of organisms to
      natural stressors is receiving an increased importance in risk assessment.
      Organisms tend to avoid extremely environmental conditions looking for optimum
      conditions. This work aimed to evaluate the effects of natural stressors on the
      energetic reserves of Daphnia magna using the quantification of lipids, proteins,
      and sugars. MATERIALS AND METHODS: Daphnids were exposed to different temperature
      regimes (16, 18, 22, 24, and 26 degrees C), food levels (2, 1.5, 1, 0.5, and 0
      and 4, 4.5, 5, 5.5, and 6 * 10(5) cells/ml Pseudokirchneriella subcapitata) and
      oxygen depletion (2 to 6 mg DO/L) and their energy reserves quantified. Protein,
      lipid, and sugar contents where compared between daphnids exposed to control
      conditions and ones exposed to considered stress situations. RESULTS AND
      DISCUSSION: Significant changes in energy reserves content after a 96-h exposure
      were observed in temperatures 16, 22, 24, and 26 degrees C. In the exposure to
      different food levels, daphnids showed significant differences on their energetic
      reserves when exposed to higher or lower levels of algae when compared with the
      control. Oxygen depletion did not affect significantly their energy budget.
      CONCLUSIONS: The results from this work demonstrate that the environmental
      alterations related mainly to temperatures variations and food availability
      produced changes in D. magna energetic reserves. These changes can be transposed
      to the population levels as they are a result of changes in the metabolic rate
      and physiological processes that are related to growth and maturation.

PMID- 21069574
TI  - Comparison of arterial stiffness and microcirculatory changes following abdominal
      aortic aneurysm grafting.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) surgery provides a unique opportunity
      to study the impact of arterial stiffness on central haemodynamics, reflected in
      augmentation index (AI). The aneurysmal aorta is significantly stiffer than
      undilated age-matched aorta. AIM: We investigated whether replacement of an
      aneurysmal aorta with a compliant graft would result in a decrease in AI, which
      would thus decrease myocardial workload parameters. METHODS: Patients undergoing
      elective open or endovascular AAA repair were assessed with applanation tonometry
      and laser fluximetry pre-operatively, immediately and long-term post-operatively.
      RESULTS: Replacement of a small segment of abnormal conduit vessel resulted in
      improvements in AI, demonstrating that arterial stiffness can be surgically
      manipulated. CONCLUSIONS: These results reflect a decreased myocardial workload
      post-aortic grafting. This decrease in AI is important from a risk factor
      management perspective, and arterial stiffness should become a further recognised
      and screened for risk factor in patients with known aneurysmal disease.

PMID- 21069575
TI  - Elevated vitamin D status in postmenopausal women on thiazolidinediones for type
      2 diabetes.
AB  - Thiazolidenediones (TZD) have been reported to lead to non-vertebral bone loss in
      postmenopausal women with diabetes, but the true incidence of vertebral fractures
      has been under-detected because two-thirds of vertebral fractures are silent. TZD
      is also related to increased adiposity, with a consequently greater risk of
      vitamin D deficiency-both of which seem to aggravate the untoward effect of TZD
      on bone. The aim of this study is to determine whether TZD use is associated with
      prevalence of vertebral fractures and low vitamin D status in postmenopausal
      women with type 2 diabetes. A group of 102 postmenopausal women with type 2
      diabetes, 52 TZD users for at least 12 months, and 50 non-TZD users were enrolled
      in the study. Any data regarding diabetes, age at menopause, co-morbidities, and
      drug use were recorded. Blood sampling and thoraco-lumbar radiography were
      performed. Bone mineral density (BMD) of L2-L4 and the femur were measured by
      dual-energy X-ray absorptiometry (DXA). The occurrence of vertebral fractures at
      one level or more in subjects on TZD was higher than those not on TZD, but did
      not reach statistical significance (19.2 vs. 14.0%, P = 0.5). Total hip BMD in
      subjects on TZD was significantly lower than those not on TZD (0.96 +/- 0.15 vs.
      1.02 +/- 0.11; P < 0.05). Levels of 25(OH)D in TZD users were significantly
      higher (35.3 +/- 1.5 vs. 25.9 +/- 1.2 ng/dl; P < 0.001). The prevalence of
      vitamin D deficiency was 75.5% in subjects not on TZD compared to 34.6% in those
      on TZD (OR 6.4, 95% CI 2.6-15.6). Higher circulating 25(OH)D was observed in TZD
      users. TZD use was associated with lower total hip BMD but not with vertebral
      fracture.

PMID- 21069576
TI  - A new mutation in the menin gene causes the multiple endocrine neoplasia type 1
      syndrome with adrenocortical carcinoma.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor
      syndrome that may be caused by mutations in the MEN1 gene on 11q13. Loss of
      function of the tumor suppressor gene MEN1 leads to synchronous or metachronous
      appearance of neuroendocrine tumors arising from neuroendocrine cells of the
      parathyroid and pituitary glands, the duodenum and pancreatic islets, and other
      endocrine organs such as the adrenal cortex. We here present a patient with MEN1
      who developed hyperparathyroidism, multiple well differentiated functionally
      inactive neuroendocrine tumors of the pancreas and an adrenal carcinoma. We
      describe a new mutation at codon 443 in the coding region of exon 9 in the MEN1
      gene, where a cytosine residue was exchanged for adenosine (TCC > TAC) and,
      consequently, serine for tyrosine (p.Ser443Tyr; c.1328C > A). [corrected] Also,
      we provide clinical data that may add to the genotype-phenotype discussion. We
      conclude that the novel mutation in the MEN1 gene described herein was clinically
      relevant.

PMID- 21069577
TI  - Contribution of change in glycosylated haemoglobin to insulin-associated weight
      gain: results of a longitudinal study in type 2 diabetic patients.
AB  - To investigate the contribution of glycosylated haemoglobin change (HbA1c) on
      body weight in patients with type 2 diabetes after start of insulin therapy. We
      analysed 122 individual weight-profiles in relation to the change in HbA1c per se
      in these patients up to 36 months after the start of insulin therapy. Data were
      analysed separately for the first 9 months after commencement of insulin therapy
      and for the period thereafter. Within the first 9 months of insulin therapy mean
      body weight increased by 0.52 kg per month. HbA1c decreased from 9.9 +/- 1.8 to
      7.9 +/- 1.3%. Only 12% of the initial weight gain could be attributed to the
      change in HbA1c. Furthermore, the mean monthly increase in body weight gain was
      reduced by 0.006 kg for every 1 kg higher body weight at baseline. From 9 to 36
      months after start of insulin therapy, body weight increased by 0.1 kg/month,
      which was independent of change in HbA1c. Improvement of glycaemic control per se
      contributes little to initial weight gain after start of insulin therapy in
      patients with T2DM. After 9 months of insulin treatment, weight gain is unrelated
      to change in glycosylated haemoglobin. Other factors have to be responsible for
      weight gain after start of insulin therapy.

PMID- 21069578
TI  - Malignant pheochromocytoma: predictive factors of malignancy and clinical course
      in 16 patients at a single tertiary medical center.
AB  - Metastases appear in approximately 10% of patients with pheochromocytoma. There
      is no predictive marker of malignancy. The aim is to describe clinical course of
      patients with malignant pheochromocytoma and to identify predictive features of
      malignancy. The method involves retrospective analysis of patients files
      diagnosed with malignant pheochromocytoma at our institution between January 1,
      1980 and December 31, 2008. We identified 16 patients with malignant
      pheochromocytoma. There were more men than women (10/6). Mean age of patients at
      time of diagnosis was 37.75-year-old. Time of occurrence of metastases ranged
      from 0 to 22 years after first diagnosis of pheochromocytoma. The mean size of
      the primary tumor was 12.1 cm. High levels of chromogranin A at the time of
      diagnosis were associated with the presence of metastases. The pheochromocytoma
      of the adrenal gland scoring scale (PASS) histological evaluation in adrenal
      primary tumors was above four in all cases but one. All patients had initial
      surgery, followed in most cases by palliative therapy: chemotherapy
      (streptozocin, cyclophosphamide-vincristine-dacarbazine, thalidomide, imatinib,
      everolimus) or (131)I-MIBG; only the latter had replicable encouraging response
      evaluation criteria in solid tumor response rates. We observed a 10-year survival
      rate of 50% after initial diagnosis of pheochromocytoma, and 25% after diagnosis
      of metastasis. Metastasis can occur very late after the initial diagnosis of
      pheochromocytoma. High chromogranin A levels may be associated with the presence
      of metastases and poor prognosis. Histological adrenal PASS higher than 4 appears
      to be suggestive of malignancy. The best therapeutic approach remains to be
      established.

PMID- 21069579
TI  - Molecular mechanism of pancreatic beta-cell adaptive proliferation: studies
      during pregnancy in rats and in vitro.
AB  - There is a widespread interest in defining factors and mechanisms that stimulate
      proliferation of pancreatic islet beta-cells. Pregnancy is a special period when
      the pancreatic islet displays a highly reproducible physiological proliferation.
      However, the molecular mechanism of beta-cell proliferation during pregnancy is
      unclear. Here, we used cDNA expression array to explore gene expression profiles
      of islet at various stages of pregnancy in rats. Differentially expressed genes
      related to islet proliferation were screened by bioinformatics methods, and
      further verified by real-time PCR, RT-PCR, and Western blotting. Compared with
      control group, expressions of hundreds of genes were changed during pregnancy.
      The differentially expressed genes related to islet proliferation were mainly
      distributed in three groups: genes involved in transcription regulator activity,
      genes involved in apoptosis or tumor, and genes for Wnt signaling pathway. Among
      these genes, expressions of Nupr1, Atf3, Btg2, beta-catenin, and c-Myc mRNA were
      up-regulated during pregnancy. A prominent expression of Nupr1 and Atf3 protein
      was observed in islets on day 10.5 of pregnancy, i.e., with earlier time phases
      than proliferation peak. Moreover, we found that prolactin (PRL) can increase the
      proliferation of beta-cell in vitro, which is accompanied by up-regulation of
      Atf3 and Nupr1, indicating that they may play a crucial role in PRL-induced
      pancreatic beta-cell growth. In conclusion, our results suggest that the
      transcription factor Nupr1, Atf3, and Wnt pathway may play an important role in
      adaptive proliferation of pancreatic islets during pregnancy in rats.

PMID- 21069580
TI  - Loss-of-function of SHARPIN causes an osteopenic phenotype in mice.
AB  - SHARPIN is a novel protein thought to interact with SHANK family and is widely
      expressed in multiple tissues/cells, including osteoblasts and osteoclasts. Loss
      of-function of Sharpin develops the chronic proliferative dermatitis mutation
      (CPDM) in mice as well as a severe inflammation in other organs. The actual
      function of SHARPIN is poorly understood. Our aim was to determine the functional
      roles of SHARPIN in bone metabolism by using CPDM mice. The skeletal phenotypes
      were determined by peripheral quantitative computed tomography, micro-computed
      tomography, and quantitative real-time RT-PCR, the cellular functions of
      osteoblasts and osteoclasts were investigated by ex vivo cell culture. Compared
      to wild-type controls, CPDM mice demonstrated significantly lower total and
      cortical bone mineral content and bone mineral density, trabecular and cortical
      bone volume, and trabecular number. The mRNA expression of Runx2, osterix, type I
      collagen, and osteocalcin was significantly lower in the bone from CPDM mice.
      Osteoclasts and osteoblasts from CPDM mice were functionally defective. Our
      result suggests that SHARPIN plays important regulating roles in bone metabolism.
      These functional roles may either come from systemic chronic inflammatory or
      directly signaling pathway within bone cells.

PMID- 21069581
TI  - Estrogen receptors similarly mediate the effects of 17beta-estradiol on cellular
      responses but differ in their potencies.
AB  - 17beta-estradiol (E2), as the main circulating estrogen hormone, plays critical
      roles in the physiology and pathophysiology of various tissues. The E2
      information is primarily conveyed by the transcription factors, estrogen
      receptors (ERs) alpha and beta. ERs share similar structural and functional
      features. Experimental studies indicate that upon binding to E2, ERs directly or
      indirectly interact with DNA and regulate gene expressions with ERalpha being
      more potent transregulator than ERbeta. However, studies also showed that ERbeta
      induces alterations in phenotypic features of cancer cell lines independent of
      E2. These observations suggested that the manner in which the unliganded ERbeta
      induces phenotypic alterations in cancer cell models differs from that of
      ERalpha. Studies demonstrated that while requiring E2 for function at low levels
      of synthesis, the unliganded ERalpha at augmented concentrations modulates gene
      expressions and cellular growth. We, therefore, anticipated that heightened
      levels of ERbeta synthesis could similarly circumvent the dependency on E2
      leading to gene transcriptions and cellular proliferation. To test this
      prediction, we used adenovirus-infected cancer cell lines in which ERs were shown
      to induce genomic and cellular responses. We found that while ERbeta at low
      levels of synthesis was dependent upon E2 for function, the receptor at high
      levels regulated gene expression and cellular proliferation independent of E2. We
      then addressed whether ERs at comparable levels that require E2 for function
      differentially alter gene expressions and cellular responses. We found that ERs
      mediate the effects of E2 on gene expression, cellular proliferation, apoptosis,
      and motility with an overlapping pattern. However, ERalpha was more potent
      regulator than ERbeta in inducing cellular responses. Our results suggest that
      differences in potencies to regulate the expression of genes are a critical
      feature of the ER subtypes in mediating E2 signaling in cancer cell lines.

PMID- 21069582
TI  - Gonadal steroids modulate Fas-induced apoptosis of lactotropes and somatotropes.
AB  - We have previously reported that Fas activation induces apoptosis of anterior
      pituitary cells from rats at proestrus but not at diestrus and in an estrogen
      dependent manner. In this study, we evaluated the effect of Fas activation on
      apoptosis of lactotropes and somatotropes during the estrous cycle and explored
      the action of gonadal steroids on Fas-induced apoptosis. Also, we studied whether
      changes in Fas expression are involved in the apoptotic response of anterior
      pituitary cells. Fas activation increased the percentage of TUNEL-positive
      lactotropes and somatotropes at proestrus but not at diestrus. FasL triggered
      apoptosis of somatotropes only when cells from ovariectomized rats were cultured
      in the presence of 17 beta-estradiol (E2). Progesterone (P4) blocked the
      apoptotic action of the Fas/FasL system in lactotropes and somatotropes incubated
      with E2. Both E2 and P4 increased the percentage of cells expressing Fas at the
      cell membrane. Our results show that Fas activation induces apoptosis of
      lactotropes and somatotropes at proestrus but not at diestrus. Gonadal steroids
      may be involved in the apoptotic response of lactotropes and somatotropes,
      suggesting that Fas activation is implicated in the renewal of these pituitary
      subpopulations during the estrous cycle. The effect of gonadal steroids on Fas
      expression may be only partially involved in regulation of the Fas/FasL apoptotic
      pathway in the anterior pituitary gland.

PMID- 21069583
TI  - Tissue-regenerating, vision-restoring corneal epithelial stem cells.
AB  - The cornea, the most anterior segment of the eye, provides us with exquisite
      vision. Unlike other vital tissues, it is poorly protected from the environment
      and is thus reliant on a self-renewal program to preserve integrity. This
      function is reserved for corneal epithelial stem cells located in the basal layer
      of the limbus, a narrow transition zone that segregates the peripheral cornea
      from the adjacent conjunctiva. Under physiological conditions, these cells
      replenish the corneal epithelium when mature or traumatized cells are lost.
      However, when the limbus is extensively damaged, stem cell activity is
      compromised, resulting in a condition known as limbal stem cell deficiency
      (LSCD). This disease is characterized by corneal neovascularization and
      persistent epithelial defects which impair vision. Over the past 20 years a
      myriad of treatment options have been developed for LSCD, most of which
      incorporate stem cell transplantation. Due to the disadvantages associated with
      the use of allogeneic and xenogeneic material, researchers are currently focusing
      on refining techniques involving autologous limbal tissue transplantation and are
      delving into the possibility that stem cells found in other organs can provide an
      alternative source of corneal epithelium. Determining where donor stem cells
      reside on the recipient's ocular surface and how long they remain viable will
      provide further insights into improving current therapeutic options for patients
      with LSCD.

PMID- 21069584
TI  - Disseminated Kikuchi disease associated with hemophagocytic syndrome in an
      infant: whole-body MRI.
AB  - We report a case of disseminated Kikuchi disease (KD) associated with
      Hemophagocytic syndrome (HS) in a 9-month-old boy with recurrent fever and tender
      cervical and inguinal lymphadenopathy. Disseminated necrotizing lymphadenopathies
      can be observed on whole-body MR imaging.

PMID- 21069585
TI  - The effect of telephone-administered cognitive-behavioral therapy on quality of
      life among patients with multiple sclerosis.
AB  - BACKGROUND: Past research has found that a variety of physical, psychological,
      and social factors can affect quality of life (QOL). These previous findings
      suggest that interventions that address these factors could potentially improve
      QOL. PURPOSE: The purpose of this study was to examine whether cognitive
      behavioral therapy (CBT) can improve QOL, and if so, explore which factors might
      mediate this effect. METHODS: This is a secondary analysis of a randomized
      controlled trial. One hundred twenty-seven participants with multiple sclerosis
      and depression were randomly assigned to either a telephone-administered CBT (T
      CBT) or telephone-administered supportive emotion-focused therapy (T-SEFT)
      intervention. RESULTS: Patients assigned to T-CBT showed significantly greater
      improvements in QOL compared with those assigned to T-SEFT. The greater
      improvement in QOL among T-CBT recipients was mediated by improvements in
      depression and positive affect. There was also inconsistent support for the
      superior effect of CBT on QOL being mediated by improvement in fatigue.
      CONCLUSIONS: T-CBT provided greater QOL benefits compared with T-SEFT, which
      controlled for non-specific treatment components. This study further suggests
      that T-CBT procedures specific to the management of depression and positive
      affect were uniquely useful in improving QOL.

PMID- 21069587
TI  - Intravascular lipoma from iliofemoral tract.
AB  - Lipoma is a benign tumour composed of well-differentiated adipocytes and is the
      most common soft tissue mass. We present a case of an intraluminal lipoma of the
      iliofemoral axis presenting as lower limb venous obstruction. In our case,
      definite diagnosis is impossible as there is aspecific symptomatology and
      radiologic imaging methods are not able to provide diriment data, considering
      rarity of the disease. Therefore, we could make correct diagnosis only
      intraoperatively. We preferred a direct reconstruction of the wall of vein. At 12
      month follow-up, we have had complete disappearance of symptoms and functional
      diseases.

PMID- 21069586
TI  - An interactive online 3D model of the heart assists in learning standard
      transesophageal echocardiography views.
AB  - PURPOSE: Transesophageal echocardiography (TEE) is becoming a standard imaging
      tool during cardiac surgery as well as an important diagnostic tool in cardiology
      and in intensive care, resulting in an increasing demand for TEE training. To
      address the problem of limited time for learning during TEE studies, we have
      developed a novel online application that allows users to visualize each of the
      20 standard diagnostic TEE views in conjunction with a three-dimensional (3D)
      heart model that can be rotated and "cut away" above the echo plane to reveal the
      internal cardiac structures. This study is an evaluation of the educational
      benefit of this application. METHODS: The application was evaluated using a pre
      test/post-test design assessing the improvement of subjects' test scores
      following three days of access to the application. The subjects were postgraduate
      fellows in anesthesia, cardiology, and cardiac surgery. RESULTS: Ten subjects
      showed a significant increase (31%) in their test scores after an average of 130
      min of access to the application over a three-day period (P < 0.001, effect size
      = 1.9). Using five-point Likert scales, the users indicated that the application
      was a useful addition to their training (4.7), they would recommend the
      application to their colleagues (4.9), and they found the application easy to use
      (4.4). CONCLUSION: The large improvement in test scores during a short period of
      study and the high level of satisfaction across all of the disciplines indicates
      that the application is a useful adjunctive tool for learning TEE. It is now
      being used in TEE training worldwide.

PMID- 21069588
TI  - Cultivation-independent assessment of bacterial viability.
AB  - Cultivation-independent assessment of bacterial viability is essential when (1)
      results are required fast and at high throughput, and/or (2) when the specific
      target or mode-of-action of a certain bactericidal process is of interest, and/or
      (3) when the organisms under investigation are regarded as "uncultivable".
      However, aside from cultivation, there exists no "silver bullet" method that
      demonstrates with absolute certainty whether an organism is alive or dead, and
      all currently available methods are prone to produce varying results with
      different organisms and in different environments. Here we discuss the
      fundamental concept of viability in bacteria, with specific focus on the main
      aspects that define it. It is argued that the presence of intact and functional
      nucleic acids, as well as an intact and polarized cytoplasmic membrane are
      essential components of cellular viability, while numerous other parameters and
      processes that are linked to viability are explored. Different methods/approaches
      are discussed with particular emphasis on the advantages and disadvantages of
      each approach, the applicability of the methods toward environmental samples, and
      the underlying link between the various viability parameters.

PMID- 21069589
TI  - Biofunctionalization of polymers and their applications.
AB  - Polyhydroxyalkanoates (PHAs) are a family of biopolyesters synthesized by many
      types of bacteria as carbon and energy reserve materials. PHAs combine properties
      of thermal processibility, biodegradability, biocompatibility and sustainability.
      They have attracted attention from fermentation, materials and biomedical
      industries. Recent environmental concerns such as CO(2) emissions and plastic
      pollution as well as rapid exhaustion of petroleum resources have increased
      public and industrial interests in these unique materials. In fact, PHA has
      slowly evolved into an industrial value chain ranging from microbial
      fermentation, bioplastic packaging, biofuel, medical implants, drug delivery,
      protein purification, chiral chemicals and drug development. This chapter will
      discuss microbial PHA production and its applications in various fields.

PMID- 21069590
TI  - Multivariate data analysis methods for the interpretation of microbial flow
      cytometric data.
AB  - Flow cytometry is an important technique in cell biology and immunology and has
      been applied by many groups to the analysis of microorganisms. This has been made
      possible by developments in hardware that is now sensitive enough to be used
      routinely for analysis of microbes. However, in contrast to advances in the
      technology that underpin flow cytometry, there has not been concomitant progress
      in the software tools required to analyse, display and disseminate the data and
      manual analysis, of individual samples remains a limiting aspect of the
      technology. We present two new data sets that illustrate common applications of
      flow cytometry in microbiology and demonstrate the application of manual data
      analysis, automated visualisation (including the first description of a new piece
      of software we are developing to facilitate this), genetic programming, principal
      components analysis and artificial neural nets to these data. The data analysis
      methods described here are equally applicable to flow cytometric applications
      with other cell types.

PMID- 21069591
TI  - Introduction: roboethics as an emerging field of ethics of technology.

PMID- 21069592
TI  - Recent trends in humanoid robotics research: scientific background, applications,
      and implications.
AB  - Even though the market size is still small at this moment, applied fields of
      robots are gradually spreading from the manufacturing industry to the others as
      one of the important components to support an aging society. For this purpose,
      the research on human-robot interaction (HRI) has been an emerging topic of
      interest for both basic research and customer application. The studies are
      especially focused on behavioral and cognitive aspects of the interaction and the
      social contexts surrounding it. As a part of these studies, the term of
      "roboethics" has been introduced as an approach to discuss the potentialities and
      the limits of robots in relation to human beings. In this article, we describe
      the recent research trends on the field of humanoid robotics. Their principal
      applications and their possible impact are discussed.

PMID- 21069593
TI  - Beyond speculative robot ethics: a vision assessment study on the future of the
      robotic caretaker.
AB  - In this article we develop a dialogue model for robot technology experts and
      designated users to discuss visions on the future of robotics in long-term care.
      Our vision assessment study aims for more distinguished and more informed visions
      on future robots. Surprisingly, our experiment also led to some promising co
      designed robot concepts in which jointly articulated moral guidelines are
      embedded. With our model, we think to have designed an interesting response on a
      recent call for a less speculative ethics of technology by encouraging
      discussions about the quality of positive and negative visions on the future of
      robotics.

PMID- 21069594
TI  - "Involving interface": an extended mind theoretical approach to roboethics.
AB  - In 2008 the authors held "Involving Interface," a lively interdisciplinary event
      focusing on issues of biological, sociocultural, and technological interfacing
      (see Acknowledgments). Inspired by discussions at this event, in this article, we
      further discuss the value of input from neuroscience for developing robots and
      machine interfaces, and the value of philosophy, the humanities, and the arts for
      identifying persistent links between human interfacing and broader ethical
      concerns. The importance of ongoing interdisciplinary debate and public
      communication on scientific and technical advances is also highlighted.
      Throughout, the authors explore the implications of the extended mind hypothesis
      for notions of moral accountability and robotics.

PMID- 21069595
TI  - Music and dementia: observing effects and searching for underlying theories.

PMID- 21069596
TI  - Efficacy of music therapy treatment based on cycles of sessions: a randomised
      controlled trial.
AB  - We undertook a randomised controlled trial to assess whether a music therapy (MT)
      scheme of administration, including three working cycles of one month spaced out
      by one month of no treatment, is effective to reduce behavioural disturbances in
      severely demented patients. Sixty persons with severe dementia (30 in the
      experimental and 30 in the control group) were enrolled. Baseline
      multidimensional assessment included demographics, Mini Mental State Examination
      (MMSE), Barthel Index and Neuropsychiatry Inventory (NPI) for all patients. All
      the patients of the experimental and control groups received standard care
      (educational and entertainment activities). In addition, the experimental group
      received three cycles of 12 active MT sessions each, three times a week. Each 30
      min session included a group of three patients. Every cycle of treatment was
      followed by one month of wash-out. At the end of this study, MT treatment
      resulted to be more effective than standard care to reduce behavioural disorders.
      We observed a significant reduction over time in the NPI global scores in both
      groups (F(7,357) = 9.06, p < 0.001) and a significant difference between groups
      (F(1,51) = 4.84, p < 0.05) due to a higher reduction of behavioural disturbances
      in the experimental group at the end of the treatment (Cohen's d = 0.63). The
      analysis of single NPI items shows that delusions, agitation and apathy
      significantly improved in the experimental, but not in the control group. This
      study suggests the effectiveness of MT approach with working cycles in reducing
      behavioural disorders of severely demented patients.

PMID- 21069597
TI  - Volunteering and older women: psychosocial and health predictors of
      participation.
AB  - OBJECTIVES: As populations age, there will be a need for more volunteers in
      social welfare, and consequently a need to better understand potential effects of
      volunteering for older people. Whilst there is a body of international literature
      exploring health benefits of volunteering in later life, there are currently no
      longitudinal studies of Australian populations. Internationally, there is a lack
      of studies focusing on older women, who comprise the majority of the ageing
      population. The aim of this article was to explore the relationship between
      volunteering and psychosocial and health factors for a cohort of older Australian
      women over time. METHOD: Data for this study were from the oldest cohort of
      Australian Longitudinal Study on Women's Health, a 20-year longitudinal survey of
      Australian women aged 70-75 years in 1996. Volunteering status was the factor of
      interest and study factors included a broad range of demographic, health and
      social factors. A longitudinal model was developed for mediators of volunteering
      over time. RESULTS: Of 7088 women in 2005, 24.5% reported actively volunteering,
      15.5% were continuing, 7.5% were new, 15.3% were intermittent and 34.7% had never
      been volunteers. Volunteering was associated with increased quality of life and
      social support. Women were more likely to continue volunteering over time if they
      lived in a rural area, had higher socioeconomic indicators, and better levels of
      physical and mental health. CONCLUSIONS: This study contributes to the literature
      on the relationship between volunteering and health for older women.
      Understanding the potential health implications of volunteering is a critical
      issue in current policy debates.

PMID- 21069598
TI  - A psychosocial model of parent fixation in people with dementia: the role of
      personality and attachment.
AB  - This study replicates and extends research into the occurrence of parent fixation
      in people with dementia by exploring the relationship between demographic,
      cognitive and psychological factors. Fifty-one people with dementia, living both
      in the community and in residential/nursing home settings, were interviewed about
      their parents and a relative of each completed measures assessing the person with
      dementia's demographic details, level of cognitive impairment/executive
      functioning, behavioural consequences of parent fixation and pre-morbid
      personality and attachment style. Results indicated that parent fixation can be
      viewed as a psychosocial phenomenon arising from the environment, pre-morbid
      personality and attachment style and that the behavioural consequences of parent
      fixation are maintained by the individual's level of executive functioning and
      gender. Findings and clinical implications are discussed in relation to Miesen's
      (1992, 1993, 1999) theoretical assumption that dementia is a loss process that
      activates the experience of feeling unsafe and the emotional need for the
      security of an attachment figure.

PMID- 21069599
TI  - Elderly people who committed suicide--their contact with the health service. What
      did they expect, and what did they get?
AB  - OBJECTIVE: Contact between elderly patients and healthcare professionals may be
      crucial for suicide prevention if suicidal tendencies are revealed and help is to
      be provided. The objective of the study was to investigate how elderly suicide
      cases had perceived the health service and what characterised their contact with
      it. METHOD: This is a psychological autopsy study based on qualitative interviews
      with people who had known 1 of the total of 23 suicide cases aged over 65. The 63
      informants were relatives, general practitioners (GPs) and home-based care
      workers. The systematic text condensation method was applied to analyse
      interviews. RESULTS: Many of the elderly expressed distrust of health service
      once their functional decline began. They feared losing their autonomy if they
      became dependent on help, and many therefore refused health service provisions.
      Communication between them and helpers failed. As they gradually became more
      dependent on medical care, many experienced that they were not given the desired
      help, which confirmed their distrust. CONCLUSION: Contact between these people
      and the health service must inspire confidence for it to prevent suicide. Elderly
      people at risk of suicide are vulnerable: they feel degraded if their autonomy is
      threatened by health personnel. The structure and organisation of the health
      service, and each worker's contact with the elderly, must preserve their dignity.
      Dignity must be evinced through the healthcare professionals' treatment of
      elderly people and a system that meets their needs.

PMID- 21069600
TI  - Videoconference program enhances social support, loneliness, and depressive
      status of elderly nursing home residents.
AB  - OBJECTIVES: The purpose of this quasi-experimental study was to evaluate the
      effectiveness of a videoconference intervention program in improving nursing home
      residents' social support, loneliness, and depressive status. METHODS: Fourteen
      nursing homes were selected from various areas of Taiwan by purposive sampling.
      Elderly residents (N = 57) of these nursing homes, who met our inclusion criteria
      were divided into experimental (n = 24) and control (n = 33) groups. The
      experimental group received five min/week of videoconference interaction with
      their family members for three months, and the control group received regular
      care only. Data were collected through face-to face interviews on social support,
      loneliness, and depressive status using the Social Supportive Behavior Scale,
      University of California Los Angeles Loneliness Scale, and Geriatric Depression
      Scale, respectively, at three points (baseline, one week, and three months after
      baseline). Data were analyzed using the generalized estimating equation approach.
      RESULTS: Subjects in the experimental group had significantly higher mean
      emotional and appraisal social support scores at one week and three months after
      baseline than those in the control group. Subjects in the experimental group also
      had lower mean loneliness scores at one week and three months after baseline than
      those in the control group, and lower mean depressive status scores at three
      months after baseline. CONCLUSION: Our videoconference program alleviated
      depressive symptoms and loneliness in elderly residents in nursing homes. Our
      findings suggest that this program could be used for residents of long-term care
      institutions, particularly those with better ability to perform activities of
      daily living.

PMID- 21069601
TI  - Depressive symptoms are associated with hospitalization, but not with mortality
      in the elderly: a population-based study.
AB  - OBJECTIVES: Subjects with depression might request more healthcare services. The
      aim of this study was to evaluate the association of depressive symptoms with
      hospitalization and mortality rates in a general unselected older population.
      METHODS: We assessed the association of the 30-items Geriatric Depression Scale
      (GDS) score with one-year hospitalization and mortality in all 344 subjects aged
      75+ living in Tuscania (Italy). This population had been enrolled in a national
      study of the genetic determinants of health status. Analyses were conducted using
      continuous, as well as categorical GDS score levels. RESULTS: After adjusting for
      potential confounders, depressive symptoms were associated in Cox regression
      modelling with hospitalization (relative risk, RR = 1.05; 95% confidence
      interval, CI = 1.01-1.09; p = 0.016), but not with mortality (RR = 1.06; 95% CI =
      0.96-1.16; p = 0.246). Increasing GDS score levels were associated with
      increasing risk of hospitalization (p for trend = 0.033). Up to 39% of
      hospitalizations might be attributed to depression. CONCLUSION: Depressive
      symptoms are not associated with increased mortality rates in general older
      populations. However, depressive symptoms represent a potentially reversible
      determinant of increased hospitalization rates in these subjects, independent of
      the presence and severity of other medical conditions.

PMID- 21069602
TI  - Confirmatory factor analysis of the Center for Epidemiologic Studies-Depression
      Scale in black and white dementia caregivers.
AB  - OBJECTIVES: In order to better understand if measurement problems underlie the
      inconsistent findings that exist regarding differences in depression levels
      between Black and White caregivers, this study examined the factor structure and
      invariance of the Center for Epidemiologic Studies-Depression (CES-D) Scale.
      METHOD: A confirmatory factor analysis of the 20-item CES-D was performed on a
      sample of 167 Black and 214 White family caregivers of older adults with dementia
      from Los Angeles County. RESULTS: The relationships between the 20 items and the
      four factors, as well as the relationships among each of the factors, were
      equivalent across both caregiver groups, indicating that the four-factor model
      fit the data for both the racial groups. CONCLUSION: These findings offer further
      evidence that the standard four-factor model is the best fitting model for the
      CES-D and is invariant across racial groups.

PMID- 21069603
TI  - Barriers to treatment and culturally endorsed coping strategies among depressed
      African-American older adults.
AB  - OBJECTIVE: Older adults are particularly vulnerable to the effects of depression,
      however, they are less likely to seek and engage in mental health treatment.
      African-American older adults are even less likely than their White counterparts
      to seek and engage in mental health treatment. This qualitative study examined
      the experience of being depressed among African-American elders and their
      perceptions of barriers confronted when contemplating seeking mental health
      services. In addition, we examined how coping strategies are utilized by African
      American elders who choose not to seek professional mental health services.
      METHOD: A total of 37 interviews were conducted with African-American elders
      endorsing at least mild symptoms of depression. Interviews were audiotaped and
      subsequently transcribed. Content analysis was utilized to analyze the
      qualitative data. RESULTS: Thematic analysis of the interviews with African
      American older adults is presented within three areas: (1) Beliefs about
      Depression Among Older African-Americans; (2) Barriers to Seeking Treatment for
      Older African-Americans; and (3) Cultural Coping Strategies for Depressed African
      American Older Adults. CONCLUSION: Older African-Americans in this study
      identified a number of experiences living in the Black community that impacted
      their treatment seeking attitudes and behaviors, which led to identification and
      utilization of more culturally endorsed coping strategies to deal with their
      depression. Findings from this study provide a greater understanding of the
      stigma associated with having a mental illness and its influence on attitudes
      toward mental health services.

PMID- 21069604
TI  - Psychological resilience predicts depressive symptoms among spouses of persons
      with Alzheimer disease over time.
AB  - This study examines the three facets of psychological resilience (i.e., perceived
      control, commitment to living, challenge versus stability) as predictors of
      depressive symptoms over time among spousal caregivers of persons with Alzheimer
      disease; these resilience factors were considered over and above dementia-related
      and socio-demographic control variables. A sample of 105 cohabiting spouses of
      persons diagnosed with probable or possible Alzheimer disease was recruited for
      this study. Multilevel modeling enabled us to examine baseline resilience, and
      the direction and magnitude of change in resilience over time, as distinct
      predictors of depressive symptoms one year later, and change in depressive
      symptoms between points of measurement. Both Time 1 control and challenge
      predicted lower levels of depressive symptoms one year later; furthermore, an
      increase in challenge over this interval predicted lower Time 2 depressive
      symptoms. In contrast, commitment did not emerge as a statistically significant
      predictor of caregiver depression. Findings of this study provide general support
      for the stress process model of caregiving; in particular, the central role of
      intra-psychic factors as significant predictors of depressive symptoms over time.

PMID- 21069605
TI  - Could hypothetical scenarios enhance understanding on decision for life
      sustaining treatment in non-demented Chinese older persons?
AB  - BACKGROUND: With increasing longevity, there is an increasing need for medical
      professionals to face situations in which explanation for decision on life
      sustaining treatment (LST) would be required. OBJECTIVES: As advance decision
      making for LST in case of severe medical illness may be unfamiliar for most of
      the Chinese elders, we aim to explore if procedures adopted to enhance the
      exposure to the issue concerned would bring about improvement in knowledge toward
      decision for LST. METHOD: This was a cross-sectional study. The design was
      divided into three sections: (i) a pre-scenario knowledge assessment, (ii)
      scenario exposure (relating issues of LST using case vignettes), and (iii) a post
      scenario assessment. The pre- and post-scenario assessment comprises 10
      questions, exploring the understanding toward basic issues related to LST. The
      scenario exposure comprises two hypothetical case vignettes describing situations
      demanding decisions for LST. The knowledge level toward LST was assessed and
      compared before and after the presentation of the two vignettes. RESULTS: One
      hundred community dwelling older persons (aged over 60 years) were recruited. The
      scenario exposure improved the knowledge level of participants (paired samples t
      test, p < 0.05). Participants who were younger and better educated were more
      likely to perform better in the knowledge test (bivariate correlation and
      logistic regression, p < 0.05). CONCLUSIONS: The results demonstrated that
      hypothetical scenarios may help to enhance and facilitate the understanding of
      LST. The study should be carried forward to explore the applicability of
      enhancement procedure to facilitate the decision making for advance directives
      and LST in the older community.

PMID- 21069607
TI  - Prevention BINGO: reducing medication and alcohol use risks for older adults.
AB  - OBJECTIVES: Older adults are a population vulnerable to the effects of alcohol,
      medication-to-alcohol interactions, and combining multiple medications. This
      study examines the effectiveness of a prevention program to increase older
      adults' knowledge about these risks. METHODS: Older adults (N = 348) were asked
      to participate in a prevention program and to take a pre- and post-test measuring
      knowledge about the risks of taking multiple medications and of alcohol use as
      one ages, before and after participation. A subsample of the group (N = 60) was
      followed at 30 days after participation in the program and asked to complete a
      survey on how the program affected their attitudes and choices regarding their
      medications and alcohol use. RESULTS: Results show a significant increase in
      knowledge about older adults' risks related to their medication and alcohol use
      from pre- to post-test. The group sampled at 30 days after program participation
      showed that the majority either agreed or strongly agreed that their attitudes
      had changed toward more awareness and increased understanding of the importance
      of knowing their risks related to medication use, medication interactions,
      multiple medications or polypharmacy, and alcohol. CONCLUSION: As a result of
      this intervention, older adults gained knowledge about their own risks related to
      medication use, medication interactions, multiple medications or polypharmacy,
      and alcohol use. Further research is needed to replicate these findings and to
      determine how prevention education can reduce these risks for older adults.

PMID- 21069606
TI  - Assessment of patient and caregiver needs in fragile X-associated tremor/ataxia
      syndrome by utilizing Q-sort methodology.
AB  - OBJECTIVES: Psychosocial stressors faced by patients with fragile X-associated
      tremor/ataxia syndrome (FXTAS) and their caregivers have not been systematically
      explored. FXTAS is a neurodegenerative disease occurring in approximately 45% of
      elderly male carriers and 8-16% of female carriers of the fragile X mental
      retardation one premutation. This study investigated the subjective needs of
      patients with FXTAS and their family caregivers, by utilizing Q-sort methodology.
      METHOD: Patients with FXTAS and their caregivers seen during January 2005 to June
      2007 participated. The Q-sort was composed of 17 (eight formal and nine informal)
      items, designed to explore emotional, informational, and instrumental needs of
      patients with FXTAS and their caregivers. Item scores were generated from 1 =
      least important to 7 = most important. Analysis included descriptive statistics
      for all the demographic and outcome variables. Generalized estimating equations
      were used to identify which of the need domains were perceived as most important
      by the participants. RESULTS: A total of 24 patients (79% men, mean age 65.6 +/-
      6.4 years) with FXTAS and 18 caregivers (11% men, mean age 63.6 +/- 6.2 years)
      completed the Q-sort. Both patients and caregivers rated informational needs as
      most important, followed by emotional and, finally, by instrumental needs.
      Participants lacked many important resources, in particular those addressing
      instrumental needs. CONCLUSION: Providers should be educated and able to provide
      timely information and referrals to formal services, as well as to informal
      resources, including the National Fragile X Foundation online support network
      (www.fragilex.org).

PMID- 21069608
TI  - Relationships among dispositional coping strategies, suicidal ideation, and
      protective factors against suicide in older adults.
AB  - Older adults have a disproportionally high rate of completed suicide as compared
      to the general population. Whereas a large literature has focused on risk factors
      related to elder suicide, limited research exists on relationships between coping
      strategies with protective factors against suicide and suicidal ideation in this
      population. Community-dwelling older adults (N = 108, mean age = 71.5 years, age
      range = 60-95 years) completed the Coping Orientations to Problems Experienced
      scale, Reasons for Living inventory, and Geriatric Suicide Ideation Scale (GSIS).
      Problem- and emotion-focused coping were associated positively with reasons for
      living and negatively with suicide ideation. Dysfunctional coping was associated
      positively with suicide ideation, but results did not support the hypothesized
      negative relationship with reasons for living. Thus, problem- and emotion-focused
      coping appear to be adaptive, whereas dysfunctional coping appears to be somewhat
      less related to resilience to suicidal ideation among community-dwelling older
      adults. Implications of the study are that some coping strategies may serve as
      protective factors against suicide and that coping strategies should be evaluated
      as part of a thorough assessment of suicidal risk among older adults. The results
      also provide some evidence of convergent validity for the recently developed
      GSIS.

PMID- 21069609
TI  - Social vulnerability, mental health and correlates of frailty in older
      outpatients living alone in the community in Italy.
AB  - OBJECTIVE: To determine the main social, functional and clinical characteristics
      of community-dwelling older outpatients living alone and to find correlates of
      frailty in this population. METHOD: Cross-sectional survey of 302 community
      dwelling outpatients aged 65+ (median age 82 years) consecutively referred to a
      geriatric medicine clinic in Italy from June to November 2009. Participants
      underwent a comprehensive geriatric assessment including frailty status evaluated
      by means of the study of osteoporotic fractures (SOF) criteria. Student's t-test
      and the chi-squared test were used to compare subjects 'living alone' and 'not
      living alone' as well as 'frail' and 'not frail' subjects among the participants
      living alone. Multiple logistic regression analyses were performed to find
      independent correlates of frailty among participants living alone. RESULTS:
      Participants 'living alone' were 124 (41%). Compared to subjects 'not living
      alone' (n = 178), they were older, received less assistance from informal and
      formal caregivers, had poorer living and financial conditions, a better cognitive
      status and functional self-sufficiency but a worse emotional status. One-third of
      them (n = 41) were frail. Among frail elders (n = 116), subjects living alone
      also showed a higher prevalence of unexpected new diagnoses of dementia than
      those not living alone. Independent correlates of frailty among participants
      living alone were: having experienced a severe acute disease in the past year
      (odds ratio [OR] 303.9; 95% confidence interval [CI] 13-7091; p < 0.001),
      dependence in the bathing BADL ability (OR 62.74; 95% CI 12.17-323.32; p <
      0.001), depression (OR 10.43; 95% CI 2.31-47.13; p = 0.002) and incontinence (OR
      3.98; 95% CI 1.01-15.66; p = 0.048). CONCLUSION: In older outpatients living
      alone, including those who were frail, we found a lower availability of personal
      assistance, significantly more social and financial vulnerability and a higher
      risk of depression. In frail elders there was also a higher prevalence of
      underdiagnosed dementia. In order to better recognise frail subjects in this
      specific population, four independent correlates of frailty were identified.

PMID- 21069611
TI  - Cognitive behavioral variables mediate the associations of neuroticism and
      attachment insecurity with Prolonged Grief Disorder severity.
AB  - Prolonged Grief Disorder (PGD) is a debilitating syndrome of grief. A recent
      cognitive behavioral model asserts that three processes are critical to this
      condition: (1) insufficient integration of the loss with autobiographical
      knowledge about the self and the lost person; (2) negative cognitions; and (3)
      anxious and depressive avoidance behaviors. These processes are assumed to
      contribute to PGD symptoms and to mediate the influence of personality-related
      vulnerabilities on the development and maintenance of these symptoms. The present
      study examined the mediational role of these three processes in the linkage
      between neuroticism, attachment anxiety, and attachment avoidance on the one hand
      and PGD symptom severity on the other hand. Self-reported data from 348 bereaved
      people were used. The results showed that the three personality variables were
      significantly associated with PGD symptom severity. Moreover, the results
      provided support for the mediating effects of indices of insufficient
      integration, negative cognitions, as well as avoidance behaviors - even after
      controlling for the shared variance between mediators. Theoretical and clinical
      implications are discussed.

PMID- 21069610
TI  - Word list memory predicts everyday function and problem-solving in the elderly:
      results from the ACTIVE cognitive intervention trial.
AB  - Data from the Advanced Cognitive Training for Independent and Vital Elderly
      (ACTIVE) trial (N = 2,802) were analyzed to examine whether word list learning
      predicts future everyday functioning. Using stepwise random effects modeling,
      measures from the modified administrations of the Hopkins Verbal Learning Test
      (HVLT) and the Auditory Verbal Learning Test (AVLT) were independently predictive
      of everyday IADL functioning, problem-solving, and psychomotor speed.
      Associations between memory scores and everyday functioning outcomes remained
      significant across follow-up intervals spanning 5 years. HVLT total recall score
      was consistently the strongest predictor of each functional outcome. Results
      suggest that verbal memory measures are uniquely associated with both current and
      future functioning and that specific verbal memory tests like the HVLT and AVLT
      have important clinical utility in predicting future functional ability among
      older adults.

PMID- 21069612
TI  - ICP-MS determination of lead isotope ratios in legal and counterfeit cigarette
      tobacco samples.
AB  - A method for the determination of Pb isotope ratios (IR) in cigarette tobacco by
      quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS) has been
      developed and applied to tobacco samples from genuine and counterfeit cigarettes
      obtained in the USA. The IR 207Pb/206Pb, (208)Pb/206Pb, 206Pb/204Pb, 207Pb/204Pb
      and 208Pb/204Pb were measured using a Q-ICP-MS instrument. Two certified
      reference materials, grown in the USA and Bulgaria, were also analysed for
      comparison with the tobacco samples, as were tobacco samples from cigarettes
      obtained in Pakistan and China. The precision of the results was sufficient to
      distinguish between the counterfeit and genuine USA cigarettes. All of the
      genuine cigarettes and both reference materials, grown in different regions, were
      statistically distinct based on the measured ratios. The counterfeit cigarettes
      were indistinguishable from the reference material grown in Bulgaria. The
      technique shows promise as a method for identifying counterfeit cigarettes,
      possibly determining the source region.

PMID- 21069613
TI  - Initial development of Minnesota Multiphasic Personality Inventory-2-Restructured
      Form (MMPI-2-RF) scales to identify patients with psychogenic nonepileptic
      seizures.
AB  - Long term video-EEG (electroencephalography) monitoring in an epilepsy monitoring
      unit (EMU) will remain the gold standard for differential diagnosis of epilepsy
      from psychogenic nonepileptic seizures. However, neuropsychologists are routinely
      part of the differential diagnosis team and utilize personality assessment
      measures to add supportive data for the diagnosis. The most accurate scale on the
      Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) in
      terms of differential diagnosis appears to be RC1 (Somatic Complaints) with a
      classification rate of 68% (Locke et al., 2010). This is not as helpful as
      neuropsychologists would like. Our aim in the current study was to determine
      whether another set of MMPI-2-RF items could provide improved classification
      accuracy. Using a combination of modern psychometric techniques and clinical
      judgment, we developed two complementary scales based on a physical complaints
      factor (Psychogenic Nonepileptic Seizures Physical Complaints, PNES-pc) and an
      attitudes factor (Psychogenic Nonepileptic Seizures Attitudes, PNES-a). The
      combination of these scales classified 73% of the sample, an improvement over
      comparable single or combined MMPI-2-RF scales. Cross validation is needed to
      warrant use in clinical practice. Information on scoring, sensitivity,
      specificity, and likelihood ratios at various levels of endorsement is provided.

PMID- 21069614
TI  - Removal of pesticides from water and wastewater by different adsorbents: a
      review.
AB  - In this review article, the use of various low-cost adsorbents for the removal of
      pesticides from water and wastewater has been reviewed. Pesticides may appear as
      pollutants in water sources, having undesirable impacts to human health because
      of their toxicity, carcinogenicity, and mutagenicity or causing aesthetic
      problems such as taste and odors. These pesticides pollute the water stream and
      it can be removed very effectively using different low-cost adsorbents. It is
      evident from a literature survey of about 191 recently published papers that low
      cost adsorbents have demonstrated outstanding removal capabilities for
      pesticides.

PMID- 21069615
TI  - Exploring in vitro/in vivo correlation: lessons learned from analyzing phase I
      results of the US EPA's ToxCast Project.
AB  - The research on alternative toxicological methods provides, among other things, a
      privileged viewpoint on one of the central issues of modern biomedical research-
      the relationship between (a) biological phenomena observed at the level of
      tissues and organisms and (b) their cellular and molecular bases as studied in
      isolated systems in vitro. The newly released ToxCast Phase 1 results, subject to
      initial analysis, converge with evidence from other fields (e.g., research on
      drug design with intensive use of omics technologies, traditional research on
      alternative tests) in indicating a low degree of the in vitro/in vivo correlation
      overall. In addition, this and other approaches point to the need for combining
      biological and chemical information in exploring the in vitro to in vivo
      connection.

PMID- 21069616
TI  - Self-reported traumatic brain injury in male young offenders: a risk factor for
      re-offending, poor mental health and violence?
AB  - Adolescence is a risk period for offending and for traumatic brain injury (TBI)
      and TBI is a risk factor for poor mental health and for offending. TBI has been
      largely neglected from guidance on managing the mental health needs of young
      offenders. We sought to determine the rate of self-reported TBI, of various
      severities, in a male, adolescent youth offending population. We also aimed to
      explore whether TBI was associated with number of convictions, violent offending,
      mental health problems and drug misuse. Young male offenders aged 11 to 19 years
      were recruited from a Young Offender Institute, a Youth Offending Team and a
      special needs school. A total of 197 participants were approached and 186 (94.4%)
      completed the study. They completed self-reports on TBI, crime history, mental
      health and drug use. TBI with loss of consciousness (LOC) was reported by 46% of
      the sample. LOC consistent with mild TBI was reported by 29.6%, and 16.6%
      reported LOC consistent with moderate to severe TBI. Possible TBI was reported by
      a further 19.1%. Repeat injury was common - with 32% reporting more than one LOC.
      Frequency of self-reported TBI was associated with more convictions. Three or
      more self-reported TBIs were associated with greater violence in offences. Those
      with self-reported TBI were also at risk of greater mental health problems and of
      misuse of cannabis. TBI may be associated with offending behaviour and worse
      mental health outcomes. Addressing TBI within adolescent offenders with
      neurorehabilitative input may be important for improving well-being and reducing
      re-offending.

PMID- 21069617
TI  - Operating characteristics of executive functioning tests following traumatic
      brain injury.
AB  - The primary purposes of this study were to determine if controls, and mild and
      moderate/severe traumatic brain injury (TBI) patients performed differently on a
      battery of executive functioning (EF) tests, and to identify the operating
      characteristics of EF tests in this population. Participants consisted of 46
      brain-injured individuals and 24 healthy controls. All participants completed an
      extensive battery of EF tests. Results showed that mild TBI participants
      performed worse than controls on the Trail Making Test Part B, and that
      moderate/severe TBI participants consistently performed worse than either group
      on a variety of EF measures. Tests of EF exhibited a wide range of operating
      characteristics, suggesting that some EF tests are better than others in
      identifying TBI-related neurocognitive impairment. Predictive values were better
      for individuals with moderate/severe TBI than mild TBI. Overall, the Digit Span
      Backward Test showed the best positive predictive power in differentiating TBI.
      Our results provide useful data that may guide test selection in evaluating EF in
      patients with traumatic brain injury.

PMID- 21069619
TI  - The effect of recognizability on figure-ground processing: does it affect parsing
      or only figure selection?
AB  - Though figure-ground assignment has been shown to be probably affected by
      recognizability, it appears sensible that object recognition must follow at least
      the earlier process of figure-ground segregation. To examine whether or not
      rudimentary object recognition could, counterintuitively, start even before the
      completion of the stage of parsing in which figure-ground segregation is done,
      participants were asked to respond, in a go/no-go fashion, whenever any out of 16
      alternative connected patterns (that constituted familiar stimuli in the upright
      orientation) appeared. The white figure of the to-be-attended stimulus-target or
      foil-could be segregated from the white ambient ground only by means of a frame
      surrounding it. Such a frame was absent until the onset of target display. Then,
      to manipulate organizational quality, the greyness of the frame was either
      gradually increased from zero (in Experiment 1) or changed abruptly to a
      stationary level whose greyness was varied between trials (in Experiments 2 and
      3). Stimulus recognizability was manipulated by orientation angle. In all three
      experiments the effect of recognizability was found to be considerably larger
      when organizational quality was minimal due to an extremely faint frame. This
      result is argued to be incompatible with any version of a serial thesis
      suggesting that processing aimed at object recognition starts only with a good
      enough level of organizational quality. The experiments rather provide some
      support to the claim, termed here "early interaction hypothesis", positing
      interaction between early recognition processing and preassignment parsing
      processes.

PMID- 21069626
TI  - [The living will declaration - expression of self-determination in health-care -
      and its legal validity for physicians].
AB  - Since September 1st 2009, the Living Will Declaration is regulated by law as held
      in SS 1901 a - c BGB. It does not need a certain format except for being in the
      written form. This must be distinguished from the right to choose a certain
      treatment according to the medical attendant and his intention to agree to or
      forbid a certain treatment. The Living Will Declaration binds the physician to
      certain clearly specified procedures that the patient has agreed to and is valid
      independently from the nature of the patient's illness or its stage because the
      basic right for self-determination (Art. 2 Abs. 2 GG) includes the right to die.
      As the physician is committed to observe the patient's will, he will have to face
      legal consequences in terms of liability and criminal law if he disregards the
      Living Will Declaration.

PMID- 21069627
TI  - [Peer-reviewed study: COPD - increases risk of pneumonia in early steroid
      therapy].

PMID- 21069628
TI  - [Behaviour therapy - a changing psychotherapeutic approach].

PMID- 21069629
TI  - [Technological intervention in the self? An ethical evaluation of deep brain
      stimulation relating to patient narratives].
AB  - Technological interventions into the brain raise a number of ethical questions,
      particularly, questions of personality change and control or manipulation of the
      human mind. Taking patients undergoing deep brain stimulation as an example, the
      authors analyse the possible impact of neurotechnologies on human self-perception
      in individual cases as well as in general. Following the concept of narrative
      based medicine and ethics patients' narrations are presented in order to discuss
      the value of this approach for developing normative considerations as well as for
      deriving practical consequences regarding the physician-patient-relationship.

PMID- 21069630
TI  - [New options in the therapeutic management of acute ischaemic stroke. Good
      results with combined i. v. and i. a. lysis and mechanical thrombectomy].
AB  - BACKGROUND: Standard therapy for acute ischaemic stroke is the intravenous
      thrombolysis with rtPA. A combined therapy with intravenous bridging and
      consecutive intraarterial thrombolysis and mechanical thrombectomy is a
      relatively new option in patients with proximal vessel occlusion. PATIENTS AND
      METHODS: 10 Patients with a CTA proven proximal vessel occlusion in the anterior
      circulation (ACI, carotis bifurcation, MCA) in CTA were treated with a combined
      therapy with i. v. and i. a. thrombolysis and thrombectomy with a Solitaire FR
      stent device. RESULTS: All Patients were recanalized, the NIHSS changed from 15.6
      to 3.3. 8 out of 10 patients had nearly no symptoms when dismissed. There were no
      direct therapeutic complications. CONCLUSION: Combined therapy with i. v. and i.
      a. thrombolysis and thombectomy with the Solitaire FR stent device is a promising
      option in patients with acute proximal vessel occlusion in the anterior
      circulation.

PMID- 21069631
TI  - [The Sex Offender Risk Appraisal Guide (SORAG)].
AB  - In North America, the use of actuarial instruments is considered to be state of
      the art in the assessment of offender recidivism risk. One of these instruments
      is the "Sex Offender Risk Appraisal Guide" (SORAG), which was developed
      specifically for the use in sex offender risk assessment. The present review
      investigates the current state of knowledge regarding the instrument's validity
      specifically for its use in German-speaking countries. Overall the results speak
      for the instrument's good discriminatory power. However, this is not true to the
      same degree for all types of sex offender populations. The discriminatory power
      is especially good in the subpopulation of child molesters. Part of the present
      review is a German translation of the instrument authorised by the developers of
      the SORAG.

PMID- 21069632
TI  - [A short summary of the history of cognitive behavioural therapy].

PMID- 21069633
TI  - Microparticles: key protagonists in cardiovascular disorders.
AB  - Microparticles (MP) are shed membrane vesicles released by various cell types
      following apoptosis or activation. MP circulate in human plasma and also
      accumulate in atherosclerotic lesions. A growing body of evidence has highlighted
      their involvement in inflammation, angiogenesis, coagulation, and the regulation
      of vascular tone. MP may therefore contribute to the initiation and development
      of atherosclerosis and its complications. Plasma MP originate from platelets,
      leukocytes, erythrocytes, and endothelial cells, and their levels increase in
      patients with cardiovascular diseases; specific cardiovascular medications also
      affect plasma MP levels. Most recent data suggest a potential prognostic role of
      circulating MP for identification of subjects prone to develop cardiovascular
      complications.

PMID- 21069634
TI  - [Colleague internet: exchange of experiences in medical communities].

PMID- 21069635
TI  - An RGD-restricted substrate interface is sufficient for the adhesion, growth and
      cartilage forming capacity of human chondrocytes.
AB  - This study aimed at testing whether an RGD-restricted substrate interface is
      sufficient for adhesion and growth of human articular chondrocytes (HAC), and
      whether it enhances their post expansion chondrogenic capacity. HAC/substrate
      interaction was restricted to RGD by modifying tissue culture polystyrene (TCPS)
      with a poly(ethylene glycol) (PEG) based copolymer system that renders the
      surface resistant to protein adsorption while at the same time presenting the
      bioactive RGD-containing peptide GCRGYGRGDSPG (RGD). As compared to TCPS, HAC
      cultured on RGD spread faster (1.9-fold), maintained higher type II collagen mRNA
      expression (4.9-fold) and displayed a 19% lower spreading area. On RGD, HAC
      attachment efficiency (66+/-10%) and proliferation rate (0.56+/-0.04
      doublings/day), as well as type II collagen mRNA expression in the subsequent
      chondrogenic differentiation phase, were similar to those of cells cultured on
      TCPS. In contrast, cartilaginous matrix deposition by HAC expanded on RGD was
      slightly but consistently higher (15% higher glycosaminoglycan-to-DNA ratio). RDG
      (bioinactive peptide) and PEG (no peptide ligand) controls yielded drastically
      reduced attachment efficiency (lower than 11%) and proliferation (lower than 0.20
      doublings/day). Collectively, these data indicate that restriction of HAC
      interaction with a substrate through RGD peptides is sufficient to support their
      adhesion, growth and maintenance of cartilage forming capacity. The concept could
      thus be implemented in materials for cartilage repair, whereby in situ
      recruited/infiltrated chondroprogenitor cells would proliferate while maintaining
      their ability to differentiate and generate cartilage tissue.

PMID- 21069636
TI  - [The effect of donepezil in comparison with conventional treatment on cognitive
      functioning and the performance of the patient in a prospective cohort of
      patients with Alzheimer's disease treated in routine clinical practice in Spain].
AB  - AIMS: Our aim was to perform a secondary analysis of a 12-month-long, non-blind,
      multi-centre prospective cost-of-illness study. The analysis assessed the effect
      of donepezil on cognitive functioning and the performance of patients with
      possible or probable Alzheimer's disease, compared to that of other drugs for
      dementia. PATIENTS AND METHODS: A sample of 700 patients took part in the study
      (76.8 +/- 6.6 years of age, 67.3% females): 600 (31.4% drug-naive) received
      donepezil and 100 (9% drug-naive) were given other drugs for dementia. RESULTS:
      The mean variations corrected by the baseline values and the centre of the total
      scores on the Folstein minimental test, the clinical dementia rating and Blessed
      dementia rating scales at 12 months were significantly lower in patients treated
      with donepezil: -1.23 +/- 3.41 versus -2.26 +/- 3.07 (p = 0.006), 0.20 +/- 0.68
      versus 0.39 +/- 1.03 (p = 0.014) and 1.28 +/- 3.31 versus 2.04 +/- 2.84 (p =
      0.027), respectively. CONCLUSIONS: This secondary analysis shows that the
      deterioration in the cognitive functioning and performance of patients with the
      passage of time is slower with donepezil than with other drugs for dementia in
      routine medical practice. Since these results were observed in a post hoc
      analysis, formal prospective clinical trials should be conducted to confirm these
      findings.

PMID- 21069637
TI  - [Latency values of 248 H reflexes in 124 normal subjects].
AB  - INTRODUCTION: The Hoffmann reflex or H reflex is an electrical counterpart of the
      myotatic reflex. In normal adults is elicited with stimulating the tibial and the
      median nerves. It is useful as an adjunct study of neuroexamination and assesses
      the corresponding arc reflexes in their integrity. SUBJECTS AND METHODS: 248 H
      reflexes were studied stimulating the tibial nerve in 124 healthy subjects.
      RESULTS: The latency values were: minimum 23.6 ms; maximum 29.8 ms; mean value
      27.6 +/- 1.41 ms. CONCLUSION: This work explains the technique to obtain the H
      reflex and discusses the need for normalized values for each neurophysiology lab.

PMID- 21069638
TI  - [Epileptic spasms without hypsarrhythmia. A new case report and review of the
      literature].
AB  - INTRODUCTION: The term 'epileptic spasm' must be used to refer to a type of
      seizure that is typically found in childhood. Clinically, it is expressed as
      brief axial contractions, in flexion, extension or mixed, which can be
      symmetrical or asymmetrical and usually appear in clusters. The best-known
      epileptic syndrome associated with the appearance of grouped spasms is West's
      syndrome. They may also appear in other generalised epilepsies, epilepsies with
      periodic spasms or even seizures that are similar to grouped spasms in certain
      partial epilepsies. CASE REPORT: A 6-month-old girl with paroxysmal episodes of
      cluster spasms, for whom no pattern of hypsarrhythmia was observed in the
      electroencephalogram. The physical examination, neuroimaging and metabolic
      studies did not offer any pathological findings of interest. The psychomotor
      development of the patient prior to the onset of the seizures was normal.
      Following treatment with several different antiepileptic drug regimes, finally
      control over the seizures was accomplished with a combination of valproic acid
      and vigabatrine. CONCLUSIONS: There are cases like this, with cluster spasms,
      which fall within the age bracket at which West's syndrome typically occurs and
      which, nevertheless, do not present the electroencephalographic characteristics
      of hypsarrhythmia (neither typical nor atypical) or neuropsychological
      impairment. In these patients it is not clear whether we are dealing with a
      variant related with West's syndrome or not, since two of the three criteria
      required for its diagnosis are not fulfilled.

PMID- 21069639
TI  - [The role of the cerebellum in the regulation of affection, emotion and
      behaviour].
AB  - INTRODUCTION: In recent decades there has been a significant increase in the
      number of articles that have drawn attention to the possible importance of the
      role of the cerebellum in non-motor functions. Schmahmann and Sherman, for
      example, have described the cognitive, behavioural and emotional pattern of what
      has been called cerebellar cognitive affective syndrome. A central aspect of this
      disorder is the dysregulation of affect that occurs when lesions involve what has
      been called the limbic cerebellum (mainly the vermis). DEVELOPMENT: A non
      systematic review of the most important literature on the role of the cerebellum
      in emotional and behavioural regulation was carried out. Two lines of analysis
      were followed. The first of them was the study of the psycho-pathological
      symptoms or neuropsychiatric disorders presented by patients suffering from
      different cerebellar pathologies ranging from congenital pathologies such as
      agenesis of the cerebellum, dysplasia or hypoplasia to other acquired diseases
      like tumours in the posterior fossa, cerebellitis or superficial siderosis. In
      such cases it has been seen that when the cerebellar vermis is compromised,
      patients display disorders affecting their behaviour and emotions, and
      psychiatric pathologies are more frequent. In the second line, we analysed the
      role played by the cerebellum in different psycho-pathological disorders in which
      the structure of the cerebellum was found to be altered. Although not universal,
      these alterations were consistent, since they involve the cerebellar vermis.
      CONCLUSIONS: Although the body of evidence continues to grow, a critical review
      of the scientific literature leads us to reflect on evolution in the study of the
      cerebral substrate underlying the cognitive functions and the evolution undergone
      by this study.

PMID- 21069640
TI  - Corticomuscular coherence behavior in fine motor control of force: a critical
      review.
AB  - INTRODUCTION: Understanding how the human motor control operates is an important
      issue to the neuroscience. One example is how the motor cortex controls muscle
      activity, which can be observed through corticomuscular coherence (CMC). AIM: Our
      study aimed to verify the influence of certain factors related to the fine motor
      control of force tasks on CMC. Our issue is if would be possible the strength of
      the coupling between the central and muscular systems measured by changes in
      oscillatory activity of beta- and gamma-band being influenced by these factors as
      much healthy subjects as patients. DEVELOPMENT: Beta-band CMC was especially
      important when executing sustaining accurate control tasks, which need more
      concentration and effort. However, we found that beta-band CMC was influenced by
      some factors. With regard to gamma-band CMC, apparently a complex and continuous
      dynamic integration of several mechanisms would be necessary to modulate gamma
      band CMC, since it was not modulated by magnitude of force. Therefore, it seems
      these mechanisms would be required to an adequate and effective neural networks
      operation when a dynamic force output is required. CONCLUSION: Beta- and gamma
      band CMC could enrich our understanding of the dynamic changes of the motor
      system not only in health subjects but also in neurological patients. It may
      serve as a sensitive index for quantifying dynamical changes in fine motor
      control of force. It has the potential to become a useful tool to characterize
      the patterns of changes in central nervous system's activities for the purposes
      of basic research, especially in restoring of motor function.

PMID- 21069641
TI  - [Calcium transport mechanisms in neuroprotection and neurotoxicity].
AB  - INTRODUCTION: Calcium (Ca2(+)) has been found to be involved in neuroprotective
      processes, by triggering enzymatic cascades that are essential for the synthesis
      and functioning of the elements that carry out this process. However, it is
      paradoxical that this ion is one of the main initiators of apoptotic cascades.
      This difference in its effects is conditioned by differences in the cytoplasmic
      concentrations. DEVELOPMENT: Ca2(+) plays a role in the activation of
      antiapoptotic signals in the neuron when its levels rise moderately, but it also
      starts apoptotic processes that are triggered mainly by its accumulation in
      mitochondria. This Ca2(+) comes from the outside or from intracellular deposits
      by means of different types of transporters. In order to assess the role of
      Ca2(+) in these processes, it is necessary to consider all the means of transport
      in an integral manner, since manipulating it pharmacologically gives rise to
      either protective or toxic processes, due to alterations in the intracellular
      concentrations of the ion. CONCLUSIONS: Notable progress has been made in the
      understanding of the effects of Ca2(+) on the central nervous system and on the
      mechanisms for controlling and transporting it. It is important to stress that
      understanding these physiological processes has led to the development of drugs
      with protective effects and, although most of them are still in the study phase
      or display important side effects, it remains a promising field that will help in
      the development of useful therapeutic strategies in neuroprotection.

PMID- 21069642
TI  - [GEITDAH consensus on attention deficit hyperactivity disorder].
AB  - In this article, the GEITDAH -the Spanish abbreviation of the Special Interest
      Group on Attention Deficit Hyper-activity Disorder (ADHD)- presents a consensus
      reached by experts in the management of ADHD from all over Spain. The consensus
      concerns fundamental aspects that should be the starting point for future local
      or regional consensus guides. Another aim of this consensus is also to reduce the
      amount of variability that occurs in the health care offered to patients with
      ADHD in our country, as well as to act as a stimulus in educational matters. That
      fact that it is not very long will make it more popular among greater numbers of
      people and this will allow these goals to be reached more effectively. The
      conclusions in the consensus guide have been constructed around an introduction
      dealing with basic aspects and recommendations for diagnosis, treatment (both
      pharmacological and psychotherapeutic), patient flow and organisational aspects.

PMID- 21069643
TI  - [Intravenous thrombolysis with tissue plasminogen activator in basilar warning
      syndrome].

PMID- 21069644
TI  - [Yawning as a clinical sign of ischaemic stroke].

PMID- 21069645
TI  - Osteoinduction by repeat plasmid injection of human bone morphogenetic protein-2.
AB  - BACKGROUND: Bone morphogenetic protein-2 (BMP-2) is an osteoinductive protein and
      is considered useful for the treatment of skeletal disorders. Previous studies
      using BMP-2 in clinical applications have encountered difficulties, including the
      lack of an efficient, safe, inexpensive and simple delivery system. The gene
      transfer approach is a promising option for utilizing BMP-2. Although viral
      vector-mediated gene transfer is efficient, safety concerns prevent its clinical
      application for common diseases. On the other hand, plasmid-based gene transfer
      is a safe method and can be harnessed for practical applications. METHODS: A
      plasmid encoding human BMP-2 (pCAGGS-BMP-2) was used and injected repeatedly (one
      to eight times) into the skeletal muscle of mice at a divided dose. We compared
      the capability of osteoinduction in the skeletal muscle of mice after gene
      transfer by repeat injection. BMP-2 production was assessed via
      immunohistochemistry, and osteoinduction was evaluated using radiography,
      histology and biochemical assays. RESULTS: The BMP-2 gene was transferred into
      the skeletal muscle of mice by repeat injection using pCAGGS-BMP-2. Mature bone
      was frequently observed in mice injected repeatedly with pCAGGS-BMP-2 at a
      divided dose. This confirms that, if the total dose is fixed, repeat injection
      with pCAGGS-BMP-2 at a divided dose causes osteoinduction more frequently in the
      skeletal muscle of mice. CONCLUSIONS: These results suggest the possibility of
      the effective clinical use of human BMP-2 gene therapy by direct DNA injection,
      and facilitate the clinical application of BMP-2 gene therapy.

PMID- 21069646
TI  - Enantioselective synthesis of 4-hydroxy-2-cyclohexenones through a multicomponent
      cyclization.

PMID- 21069647
TI  - A well-defined iron catalyst for the reduction of bicarbonates and carbon dioxide
      to formates, alkyl formates, and formamides.

PMID- 21069648
TI  - Transition-metal-promoted chemoselective photoreactions at the cucurbituril rim.

PMID- 21069649
TI  - Synthetic and theoretical investigations of myrmicarin biosynthesis.

PMID- 21069653
TI  - A time-dependent picture of the ultrafast deactivation of keto-cytosine including
      three-state conical intersections.
AB  - Using mixed quantum-classical dynamics, the lowest part of the UV absorption
      spectrum and the first deactivation steps of keto-cytosine have been
      investigated. The spectrum shows several strong peaks, which mainly come from the
      S(1) and S(2) states, with minor contributions from the S(3). The semiclassical
      trajectories, launched from these three states, clearly indicate that at least
      four states are involved in the relaxation of keto-cytosine to the ground state.
      Non-adiabatic transfer between the pipi* and npi* excited states and deactivation
      via three-state conical intersections is observed in the very early stage of the
      dynamics. In less than 100 fs, a large amount of population is deactivated to the
      ground state via several mechanisms; some population remains trapped in the S(2)
      state. The latter two events can be connected to the fs and ps transients
      observed experimentally.

PMID- 21069654
TI  - Real-time probing of ion pairing dynamics with 2DIR spectroscopy.
AB  - Chemical exchange two-dimensional infrared (2DIR) spectroscopy is applied to
      investigate ion pairing dynamics occurring on picosecond timescales. SeCN(-) ion
      is used as a vibrational probe. The SeCN(-) ion dissolved in N,N-dimethyl
      formamide (DMF) has a sufficiently long vibrational lifetime and can form a
      contact ion pair with Li(+) ion in DMF. The CN stretch frequency of the contact
      ion pair is significantly blue-shifted from that of free SeCN(-) so the free
      SeCN(-) ion can be spectrally distinct from the contact ion pair in DMF.
      Therefore, we were able to directly monitor the ion pairing dynamics of Li(+) and
      SeCN(-) in real time by using ultrafast 2DIR spectroscopy. As a result, we have
      determined the dissociation time constant of the LiSeCN contact ion pair to be
      420+/-40 ps.

PMID- 21069656
TI  - Structure-activity relationship study of 16 a-thiocamptothecins: an integrated in
      vitro and in silico approach.
AB  - The instability of the hydroxylactone E ring represents a critical drawback of
      camptothecins, because the lactone ring is recognized to be essential for
      stabilization of topoisomerase I-mediated DNA cleavage. In an attempt to
      investigate the effect of the thiopyridone pharmacophofore on the molecular and
      pharmacological features of the drug, we prepared a series of novel 16 a
      thiocamptothecin analogues. Due to the sulfur atom, a destabilization of the
      hydrogen bond between the hydroxy group in position 17 of the opened E ring and
      the carbonyl of the pyridone moiety is predicted, thus shifting the equilibrium
      toward the closed lactone form and increasing the lipophilic properties of the
      compounds. This feature was associated with superior antiproliferative potency,
      with reduced interaction with the human serum albumin and with substantial
      increase of the persistence of the topoisomerase I-DNA cleavable complex. These
      effects were prominent for thio-SN38, the most active compound of the series. The
      favorable interactions at the molecular and cellular level of the reported
      thiocamptothecins confer promising features, and these compounds warrant
      preclinical development.

PMID- 21069657
TI  - 1-Cyclohexyl-4-(4-arylcyclohexyl)piperazines: Mixed sigma and human Delta(8)
      Delta(7) sterol isomerase ligands with antiproliferative and P-glycoprotein
      inhibitory activity.
AB  - Many new chemotherapeutic agents are under preclinical investigation and, despite
      efforts to more selectively target cancer cells, limitations such as toxicity and
      inherent resistance are often encountered. Therefore, alternative strategies are
      needed to treat cancer and overcome such limitations. We describe novel
      cyclohexylpiperazine derivatives, designed as mixed affinity ligands for sigma
      (sigma) receptors and human Delta8-Delta7 sterol isomerase (HSI) ligands, which
      also exhibit P-glycoprotein (P-gp) inhibitory activity, with the aim of
      exploiting the antiproliferative effects mediated by sigma and HSI sites while
      overcoming P-gp-mediated resistance. All of the compounds displayed high
      affinities for sigma receptors and HSI sites, P-gp inhibitory activity, and
      sigma2 receptor agonist antiproliferative activity. Antiproliferative activity
      was also tested in PC-3 cells to establish sigma1 and HSI contribution. Compound
      cis-11, which displayed the best antiproliferative and P-gp inhibitory
      activities, was co-administered with 0.1 MUM doxorubicin in MDCK-MDR1 cells.
      Compound cis-11 caused 70 % and 90 % cell death when co-administered at 30 MUM
      and 50 MUm, respectively. When administered alone, cis-11 resulted in 50 % cell
      death, demonstrating its single agent antitumor properties in a tumor cell line
      overexpressing P-gp.

PMID- 21069658
TI  - New Insights on the mechanism of PPAR-targeted drugs.

PMID- 21069660
TI  - Characterization of anion exchange ionomers in hybrid polymer electrolyte fuel
      cells.
AB  - Anion exchange ionomers (AEI) synthesized here were characterized by use of a
      novel fuel cell configuration. The new analysis method involves assembling the
      AEI electrode of interest as the cathode in a hybrid, acid/alkaline, fuel cell
      configuration. The hybrid cell includes a conventional proton conducting
      anode/membrane half-cell along with the anionic conductor of interest at the
      cathode. Electrochemical impedance spectroscopy and voltammetry were used to
      evaluate the performance of the hybrid AEI-containing fuel cell with H2 and O2.
      In particular, the AEI electrode response in impedance spectroscopy was easily
      identified because the contributions from other components are largely minimized
      in the presented hybrid cell configuration. The properties of ionomers used in
      the AEI electrode were shown to have a substantial effect on the electrode
      performance. Low catalyst utilization, due to high water uptake and low
      conductivity, was identified as the major causes of poor performance in AEI
      electrodes.

PMID- 21069661
TI  - Synthesis of carbon-based solid acid microspheres and their application to the
      production of biodiesel.

PMID- 21069662
TI  - Advances in analysis of transcriptional regulatory networks.
AB  - A transcriptional regulatory network represents a molecular framework in which
      developmental or environmental cues are transformed into differential expression
      of genes. Transcriptional regulation is mediated by the combinatorial interplay
      between cis-regulatory DNA elements and trans-acting transcription factors, and
      is perhaps the most important mechanism for controlling gene expression. Recent
      innovations, most notably the method for detecting protein-DNA interactions
      genome-wide, can help provide a comprehensive catalog of cis-regulatory elements
      and their interaction with given trans-acting factors in a given condition. A
      transcriptional regulatory network that integrates such information can lead to a
      systems-level understanding of regulatory mechanisms. In this review, we will
      highlight the key aspects of current knowledge on eukaryotic transcriptional
      regulation, especially on known transcription factors and their interacting
      regulatory elements. Then we will review some recent technical advances for
      genome-wide mapping of DNA-protein interactions based on high-throughput
      sequencing. Finally, we will discuss the types of biological insights that can be
      obtained from a network-level understanding of transcription regulation as well
      as future challenges in the field.

PMID- 21069663
TI  - Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.
AB  - BACKGROUND: Eclampsia, the occurrence of a seizure (fit) in association with pre
      eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the
      drug of choice for treating eclampsia. This review assesses its use for
      preventing eclampsia. OBJECTIVES: To assess the effects of magnesium sulphate,
      and other anticonvulsants, for prevention of eclampsia. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June
      2010), and the Cochrane Central Register of Controlled Trials Register (The
      Cochrane Library 2010, Issue 3). SELECTION CRITERIA: Randomised trials comparing
      anticonvulsants with placebo or no anticonvulsant, or comparisons of different
      drugs, for pre-eclampsia. DATA COLLECTION AND ANALYSIS: Two authors assessed
      trial quality and extracted data independently. MAIN RESULTS: We included 15
      trials. Six (11,444 women) compared magnesium sulphate with placebo or no
      anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk
      ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to
      treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a
      non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no
      clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It
      reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100,
      95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to
      1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04,
      95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with
      magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to
      treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was
      reported by one trial comparing magnesium sulphate with placebo: for 3375 women
      there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or
      morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26)
      (median follow-up 26 months); for 3283 children exposed in utero there was no
      clear difference in death (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory
      disability (RR 0.77, 95% CI 0.38 to 1.58) at age 18 months.Magnesium sulphate
      reduced eclampsia compared to phenytoin (three trials, 2291 women; RR 0.08, 95%
      CI 0.01 to 0.60) and nimodipine (one trial, 1650 women; RR 0.33, 95% CI 0.14 to
      0.77). AUTHORS' CONCLUSIONS: Magnesium sulphate more than halves the risk of
      eclampsia, and probably reduces maternal death. There is no clear effect on
      outcome after discharge from hospital. A quarter of women report side effects
      with magnesium sulphate.

PMID- 21069664
TI  - WITHDRAWN: Antihistamines versus aspirin for itching in late pregnancy.
AB  - BACKGROUND: While not common, itching in pregnancy (not due to liver disease) can
      be distressing. OBJECTIVES: The objective of this review was to assess the
      effects of treatment for itching in late pregnancy. SEARCH STRATEGY: We searched
      the Cochrane Pregnancy and Childbirth Group trials register (January 2007).
      SELECTION CRITERIA: Randomised trials of treatments for itching in women in late
      pregnancy with normal liver function. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trial quality and extracted data. MAIN RESULTS:
      One study of 38 women was included. This was a small crossover trial, using
      alternate allocation. The trial compared a histamine, chlorpheniramine, with
      aspirin. Aspirin was more effective than chlorpheniramine in relieving itching
      (odds ratio 2.39, 95% confidence interval 1.25 to 4.57). However,
      chlorpheniramine was more effective than aspirin when a rash was present.
      AUTHORS' CONCLUSIONS: Aspirin appears to be more effective than chlorpheniramine
      for relief of itching in pregnancy when no rash is present. If there is a rash,
      chlorpheniramine may be more effective.

PMID- 21069665
TI  - WITHDRAWN: Vacuum extraction versus forceps for assisted vaginal delivery.
AB  - BACKGROUND: Proponents of vacuum delivery argue that it should be chosen first
      for assisted vaginal delivery, because it is less likely to injure the mother.
      OBJECTIVES: The objective of this review was to assess the effects of vacuum
      extraction compared to forceps, on failure to achieve delivery and maternal and
      neonatal morbidity. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register. Date of last search: February 1999. SELECTION
      CRITERIA: Acceptably controlled comparisons of vacuum extraction and forceps
      delivery. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. Study authors were contacted for additional
      information. MAIN RESULTS: Ten trials were included. The trials were of
      reasonable quality. Use of the vacuum extractor for assisted vaginal delivery
      when compared to forceps delivery was associated with significantly less maternal
      trauma (odds ratio 0.41, 95% confidence interval 0.33 to 0.50) and with less
      general and regional anaesthesia. There were more deliveries with vacuum
      extraction (odds ratio 1.69, 95% confidence interval 1.31 to 2.19). Fewer
      caesarean sections were carried out in the vacuum extractor group. However the
      vacuum extractor was associated with an increase in neonatal cephalhaematomata
      and retinal haemorrhages. Serious neonatal injury was uncommon with either
      instrument. AUTHORS' CONCLUSIONS: Use of the vacuum extractor rather than forceps
      for assisted delivery appears to reduce maternal morbidity. The reduction in
      cephalhaematoma and retinal haemorrhages seen with forceps may be a compensatory
      benefit.

PMID- 21069666
TI  - WITHDRAWN: Soft versus rigid vacuum extractor cups for assisted vaginal delivery.
AB  - BACKGROUND: The original cups used for vacuum extraction delivery of the fetus
      were rigid metal cups. Subsequently, soft cups of flexible materials such as
      silicone rubber or plastic were introduced. Soft cups are thought to have a
      poorer success rate than metal cups. However they are also thought to be less
      likely to be associated with scalp trauma and less likely to injure the mother.
      OBJECTIVES: The objective of this review was to assess the effects of soft versus
      rigid vacuum extractor cups on perineal injury, fetal scalp injury and success
      rate. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group
      trials register and the Cochrane Controlled Trials Register. Date of last search:
      February 2000. SELECTION CRITERIA: Acceptably controlled comparisons of soft
      versus rigid vacuum extractor cups. DATA COLLECTION AND ANALYSIS: Two reviewers
      assessed trial quality and extracted data. Study authors were contacted for
      additional information. MAIN RESULTS: Nine trials involving 1375 women were
      included. The trials were of average quality. Soft cups are significantly more
      likely to fail to achieve vaginal delivery (odds ratio 1.65, 95% confidence
      interval 1.19 to 2.29). However, they were associated with less scalp injury
      (odds ratio 0.45, 95% confidence interval 0.15 to 0.60). There was no difference
      between the two groups in terms of maternal injury. AUTHORS' CONCLUSIONS: Metal
      cups appear to be more suitable for 'occipito-posterior', transverse and
      difficult 'occipito-anterior' position deliveries. The soft cups seem to be
      appropriate for straightforward deliveries.

PMID- 21069667
TI  - Mass media interventions for preventing smoking in young people.
AB  - BACKGROUND: The mass media have been used as a way of delivering preventive
      health messages. They have the potential to reach and to modify the knowledge,
      attitudes and behaviour of a large proportion of the community. OBJECTIVES: To
      evaluate the effectiveness of mass media interventions to prevent smoking in
      young people in terms of reduced smoking uptake, in addition to secondary
      outcomes including improved smoking outcomes, attitudes, behaviours, knowledge,
      self-efficacy and perception. SEARCH STRATEGY: We searched the Cochrane Tobacco
      Addiction Group Specialised Register and conducted additional searches of MEDLINE
      and EMBASE in July 2010. SELECTION CRITERIA: Randomized trials, controlled trials
      without randomization and time series studies that assessed the effectiveness of
      mass media campaigns (defined as channels of communication such as television,
      radio, newspapers, bill boards, posters, leaflets or booklets intended to reach
      large numbers of people and which are not dependent on person to person contact)
      in influencing the smoking behaviour (either objective or self-reported) of young
      people under the age of 25 years. DATA COLLECTION AND ANALYSIS: Information
      relating to the characteristics and the content of media interventions,
      participants, outcomes, methods of the study and risk of bias was abstracted by
      two independent reviewers. Studies were combined using qualitative narrative
      synthesis. MAIN RESULTS: Seven out of a total of 84 studies reporting information
      about mass media smoking campaigns met all of the inclusion criteria. All seven
      studies used a controlled trial design. Three studies concluded that mass media
      reduced the smoking behaviour of young people. All of the effective campaigns had
      a solid theoretical basis, used formative research in designing the campaign
      messages, and message broadcast was of reasonable intensity over extensive
      periods of time. AUTHORS' CONCLUSIONS: There is some evidence that mass media can
      prevent the uptake of smoking in young people, however the evidence is not strong
      and contains a number of methodological flaws.

PMID- 21069668
TI  - Injectable vaccines for preventing pneumococcal infection in patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: As chronic obstructive pulmonary disease (COPD) progresses,
      exacerbations can occur with increasing frequency. One goal of therapy is to
      prevent these exacerbations, thereby reducing morbidity and associated healthcare
      costs. Pneumococcal vaccinations are one strategy for reducing the risk of
      infective exacerbations. OBJECTIVES: To determine the safety and efficacy of
      pneumococcal vaccination in COPD. The primary outcomes assessed were episodes of
      pneumonia and acute exacerbations. Secondary outcomes of interest included
      hospital admissions, adverse events related to treatment, disability, change in
      lung function, mortality, and cost effectiveness. SEARCH STRATEGY: We searched
      the Cochrane Airways Group COPD trials register and the databases CENTRAL,
      MEDLINE and EMBASE using pre-specified terms. The latest searches were performed
      in March 2010. SELECTION CRITERIA: Randomised controlled trials assessing the
      effects of injectable pneumococcal vaccine in people with COPD were included.
      DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      three review authors independently assessed trial quality. MAIN RESULTS: Seven
      studies were identified that met the inclusion criteria for this review and were
      included in the 2010 review update. Two older trials used a 14-valent vaccine and
      five more recent trials used a 23-valent injectable vaccine.In six studies
      involving 1372 people, the reduction in likelihood of developing pneumonia with
      pneumococcal vaccination compared to control did not achieve statistical
      significance, the odds ratio (OR) was 0.72 (95% confidence interval (CI) 0.51 to
      1.01), with moderate heterogeneity present between studies. The reduction in
      likelihood of acute exacerbations of COPD from two studies involving 216 people
      was not statistically significant (Peto OR 0.58; 95% CI 0.30 to 1.13).Of the
      secondary outcomes for which data were available there was no statistically
      significant effect for reduction in hospital admissions (two studies) or
      emergency department visits (one study). There was no significant reduction in
      pooled results from three studies involving 888 people for odds of all-cause
      mortality for periods up to 48 months post-vaccination (OR 0.94; 95% CI 0.67 to
      1.33), or for death from cardiorespiratory causes (OR 1.07; 95% CI 0.69 to 1.66).
      AUTHORS' CONCLUSIONS: The limited evidence from randomised controlled trials
      (RCTs) included in this review suggests that, while it is possible that
      injectable polyvalent pneumococcal vaccines may provide some protection against
      morbidity in persons with COPD, no significant effect on any of the outcomes was
      shown. Further large RCTs in this population would be needed to confirm
      effectiveness of the vaccine suggested by results from longitudinal studies.

PMID- 21069669
TI  - WITHDRAWN: Vitamin A supplementation during pregnancy.
AB  - BACKGROUND: Vitamin A supplements have been recommended in pregnancy to improve
      outcomes that include maternal mortality and morbidity. OBJECTIVES: To review the
      effectiveness of vitamin A supplementation during pregnancy, alone or in
      combination with other supplements, on maternal and newborn clinical and
      laboratory outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's specialised register of controlled trials (April 2002) and the
      Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2002).
      SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating the
      effect of vitamin A supplementation in pregnant women. The types of intervention
      included vitamin A supplementation alone or in combination with other micro
      nutrients. DATA COLLECTION AND ANALYSIS: We assessed trials for methodological
      quality using the standard Cochrane criteria of adequacy of concealment. At least
      two review authors independently assessed the trials for inclusion and extracted
      data. We collected information on blinding, loss to follow-up, setting, number of
      women, exclusion after randomisation and follow-up as well as supplementation
      type, dose and frequency. The outcomes we sought included maternal and neonatal
      clinical and laboratory outcomes. MAIN RESULTS: Five trials involving 23,426
      women were included. Because the trials were heterogeneous with regard to type of
      supplement given, duration of supplement use and outcomes measured, pooled
      results using meta analysis could not be performed. One large population based
      trial in Nepal showed a possible beneficial effect on maternal mortality after
      weekly vitamin A supplements. In this study a reduction was noted in all cause
      maternal mortality up to 12 weeks postpartum with Vitamin A supplementation (RR
      0.60, 95% CI 0.37-0.97). Night-blindness was assessed in a nested case-control
      study within this trial and found to be reduced but not eliminated. Three trials
      examined the effect of vitamin A supplementation on haemoglobin levels. The trial
      from Indonesia showed a beneficial effect in women who were anaemic ([Hb] <11.0
      g/dl). After supplementation, the proportion of women who became non-anaemic was
      35% in the Vitamin A supplemented group, 68% in the iron-supplemented group, 97%
      in the group supplemented with both Vitamin A and iron and 16% in the placebo
      group. The two trials from Malawi did not corroborate these positive findings.
      AUTHORS' CONCLUSIONS: Although the two trials from Nepal and Indonesia suggested
      beneficial effects of vitamin A supplementation, further trials are needed to
      determine whether vitamin A supplements can reduce maternal mortality and
      morbidity and by what mechanism.

PMID- 21069670
TI  - Short-term treatment with proton pump inhibitors, H2-receptor antagonists and
      prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy
      negative reflux disease.
AB  - BACKGROUND: Approximately 25% of adults regularly experience heartburn, a symptom
      of gastro-oesophageal reflux disease (GORD). Most patients are treated
      empirically (without specific diagnostic evaluation e.g. endoscopy. Among
      patients who have an upper endoscopy, findings range from a normal appearance,
      mild erythema to severe oesophagitis with stricture formation. Patients without
      visible damage to the oesophagus have endoscopy negative reflux disease (ENRD).
      The pathogenesis of ENRD, and its response to treatment may differ from GORD with
      oesophagitis. OBJECTIVES: Summarise, quantify and compare the efficacy of short
      term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and
      prokinetics in adults with GORD, treated empirically and in those with endoscopy
      negative reflux disease (ENRD). SEARCH STRATEGY: We searched MEDLINE (January
      1966 to November 2008), EMBASE (January 1988 to November 2008), and EBMR in
      November 2008. SELECTION CRITERIA: Randomised controlled trials reporting
      symptomatic outcome after short-term treatment for GORD using proton pump
      inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be
      either from an empirical treatment group (no endoscopy used in treatment
      allocation) or from an endoscopy negative reflux disease group (no signs of
      erosive oesophagitis). DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. MAIN RESULTS: Thirty-two trials (9738
      participants) were included: fifteen in the empirical treatment group, thirteen
      in the ENRD group and four in both. In empirical treatment of GORD the relative
      risk (RR) for heartburn remission (the primary efficacy variable) in placebo
      controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32
      to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics
      0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more
      effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics
      (two trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, the RR for
      heartburn remission for PPI versus placebo was 0.73 (eight trials, 95% CI 0.67 to
      0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The
      RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI
      versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). AUTHORS' CONCLUSIONS:
      PPIs are more effective than H2RAs in relieving heartburn in patients with GORD
      who are treated empirically and in those with ENRD, although the magnitude of
      benefit is greater for those treated empirically.

PMID- 21069671
TI  - Prophylactic mastectomy for the prevention of breast cancer.
AB  - BACKGROUND: Recent progress in understanding the genetic basis of breast cancer
      has increased interest in prophylactic mastectomy (PM) as a method of preventing
      breast cancer. OBJECTIVES: (i) To determine whether prophylactic mastectomy
      reduces death rates from any cause in women who have never had breast cancer and
      in women who have a history of breast cancer in one breast, and (ii) to examine
      the effect of prophylactic mastectomy on other endpoints, including breast cancer
      incidence, breast cancer mortality, disease-free survival, physical morbidity,
      and psychosocial outcomes. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL, 2002), MEDLINE and Cancerlit (1966 to
      June 2006), EMBASE (1974 to June 2006), and the WHO International Clinical Trials
      Registry Platform (WHO ICTRP) search portal (until June 2006). Studies in English
      were included. SELECTION CRITERIA: Participants included women at risk for breast
      cancer in at least one breast. Interventions included all types of mastectomy
      performed for the purpose of preventing breast cancer. DATA COLLECTION AND
      ANALYSIS: At least two authors independently abstracted data. Data were
      summarized descriptively; quantitative meta-analysis was not feasible due to
      heterogeneity of study designs and insufficient reporting. Data were analyzed
      separately for bilateral prophylactic mastectomy (BPM) and contralateral
      prophylactic mastectomy (CPM). MAIN RESULTS: All 39 included studies were
      observational studies with some methodological limitations; randomized trials
      were absent. The studies presented data on 7,384 women with a wide range of risk
      factors for breast cancer who underwent PM.BPM studies on the incidence of breast
      cancer and/or disease-specific mortality reported reductions after BPM
      particularly for those with BRCA1/2 mutations. For CPM, studies consistently
      reported reductions in incidence of contralateral breast cancer but were
      inconsistent about improvements in disease-specific survival. Only one study
      attempted to control for multiple differences between intervention groups and
      this study showed no overall survival advantage for CPM at 15 years. Another
      study showed significantly improved survival following CPM but after adjusting
      for bilateral prophylactic oophorectomy, the CPM effect on all-cause mortality
      was no longer significant.Sixteen studies assessed psychosocial measures; most
      reported high levels of satisfaction with the decision to have PM but more
      variable satisfaction with cosmetic results. Worry over breast cancer was
      significantly reduced after BPM when compared both to baseline worry levels and
      to the groups who opted for surveillance rather than BPM.Case series reporting on
      adverse events from PM with or without reconstruction reported rates of
      unanticipated re-operations from 4% in those without reconstruction to 49% in
      patients with reconstruction. AUTHORS' CONCLUSIONS: Sixteen studies have been
      published since the last version of the review, without altering our conclusions.
      While published observational studies demonstrated that BPM was effective in
      reducing both the incidence of, and death from, breast cancer, more rigorous
      prospective studies (ideally randomized trials) are needed. BPM should be
      considered only among those at very high risk of disease. There is insufficient
      evidence that CPM improves survival and studies that control for multiple
      confounding variables are needed.

PMID- 21069672
TI  - Electromagnetic therapy for treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers are defined as areas "of localized damage to the skin
      and underlying tissue caused by pressure, shear, friction and/or the combination
      of these". Electromagnetic therapy (EMT), in which electrodes produce an
      electromagnetic field across the wound, may improve healing of chronic wounds
      such as pressure ulcers. OBJECTIVES: To assess the effects of EMT on the healing
      of pressure ulcers. SEARCH STRATEGY: For this update we searched the Cochrane
      Wounds Group Specialised Register (2 June 2010); the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2); Ovid MEDLINE
      (2007 to May Week 3 2010); Ovid EMBASE (2007 to Week 21 2010) and EBSCO CINAHL
      (2007 to 1 June 2010). SELECTION CRITERIA: Randomised controlled trials comparing
      EMT with sham EMT or other (standard) treatment. DATA COLLECTION AND ANALYSIS:
      For this update two review authors independently scrutinised the results of the
      search to identify relevant RCTs and obtained full reports of potentially
      eligible studies. We made attempts to obtain missing data by contacting study
      authors. A second review author checked data extraction and disagreements were
      resolved after discussion between review authors. MAIN RESULTS: We identified no
      new trials for this update.Two randomised controlled trials (RCTs), involving 60
      participants, at unclear risk of bias were included in the original review. Both
      trials compared the use of EMT with sham EMT, although one of the trials included
      a third arm in which only standard therapy was applied. Neither study found a
      statistically significant difference in complete healing in people treated with
      EMT compared with those in the control group. In one trial that assessed
      percentage reduction in wound surface area, the difference between the two groups
      was reported to be statistically significant in favour of EMT. However, this
      result should be interpreted with caution as this is a small study and this
      finding may be due to chance. Additionally, the outcome, percentage reduction in
      wound area, is less clinically meaningful than complete healing. AUTHORS'
      CONCLUSIONS: The results provide no strong evidence of benefit in using EMT to
      treat pressure ulcers. However, the possibility of a beneficial or harmful effect
      cannot be ruled out because there were only two included trials, both with
      methodological limitations and small numbers of participants. Further research is
      recommended.

PMID- 21069673
TI  - Probiotics for treating acute infectious diarrhoea.
AB  - BACKGROUND: Probiotics may offer a safe intervention in acute infectious
      diarrhoea to reduce the duration and severity of the illness. OBJECTIVES: To
      assess the effects of probiotics in proven or presumed acute infectious
      diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's
      trials register (July 2010), the Cochrane Controlled Trials Register (The
      Cochrane Library Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1988 to
      July 2010), and reference lists from studies and reviews. We also contacted
      organizations and individuals working in the field, and pharmaceutical companies
      manufacturing probiotic agents. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials comparing a specified probiotic agent with a placebo
      or no probiotic in people with acute diarrhoea that is proven or presumed to be
      caused by an infectious agent. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the methodological quality of the trial and extracted
      data. Primary outcomes were the mean duration of diarrhoea, stool frequency on
      day 2 after intervention and ongoing diarrhoea on day 4. A random-effects model
      was used. MAIN RESULTS: Sixty-three studies met the inclusion criteria with a
      total of 8014 participants. Of these, 56 trials recruited infants and young
      children. The trials varied in the definition used for acute diarrhoea and the
      end of the diarrhoeal illness, as well as in the risk of bias. The trials were
      undertaken in a wide range of different settings and also varied greatly in
      organisms tested, dosage, and participants' characteristics. No adverse events
      were attributed to the probiotic intervention.Probiotics reduced the duration of
      diarrhoea, although the size of the effect varied considerably between
      studies.The average of the effect was significant for mean duration of diarrhoea
      (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n=4555,
      trials=35) diarrhoea lasting >=4 days (risk ratio 0.41; 0.32 to 0.53; n=2853,
      trials=29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14;
      n=2751, trials=20).The differences in effect size between studies was not
      explained by study quality, probiotic strain, the number of different strains,
      the viability of the organisms, dosage of organisms, the causes of diarrhoea, or
      the severity of the diarrhoea, or whether the studies were done in developed or
      developing countries. AUTHORS' CONCLUSIONS: Used alongside rehydration therapy,
      probiotics appear to be safe and have clear beneficial effects in shortening the
      duration and reducing stool frequency in acute infectious diarrhoea. However,
      more research is needed to guide the use of particular probiotic regimens in
      specific patient groups.

PMID- 21069674
TI  - Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma
      exchange for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is a
      disease causing progressive or relapsing and remitting weakness and numbness. It
      is probably due to an autoimmune process. Immunosuppressive or immunomodulatory
      drugs would be expected to be beneficial. OBJECTIVES: We aimed to review
      systematically the evidence from randomised trials of cytotoxic drugs and
      interferons other than corticosteroids, immunoglobulin and plasma exchange for
      chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group Specialised Register (May
      2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, Issue 2), MEDLINE (January 1977 to May 2010), EMBASE (January 1980 to
      May 2010), CINAHL (January 1982 to May 2010) and LILACS (January 1982 to May
      2010). We contacted the authors of the trials identified and other disease
      experts seeking other published and unpublished trials. SELECTION CRITERIA: We
      sought randomised and quasi-randomised trials of all immunosuppressive agents
      such as azathioprine, cyclophosphamide, methotrexate, ciclosporin A,
      mycophenolate mofetil, and rituximab and all immunomodulatory agents such as
      interferon alfa and interferon beta in participants fulfilling standard
      diagnostic criteria for chronic inflammatory demyelinating
      polyradiculoneuropathy. DATA COLLECTION AND ANALYSIS: Two authors independently
      selected trials, judged their methodological quality and extracted data. We
      wanted to measure the change in disability after one year as our primary outcome.
      Our secondary outcomes were change in disability after four or more weeks (from
      randomisation), change in impairment after at least one year, change in maximum
      motor nerve conduction velocity and compound muscle action potential amplitude
      after one year and for those participants who were receiving corticosteroids or
      intravenous immunoglobulin, the amount of this medication given during at least
      one year after randomisation. Participants with one or more serious adverse
      events during the first year was also a secondary outcome. MAIN RESULTS: Four
      trials fulfilled the selection criteria, one of azathioprine (27 participants),
      two of interferon beta-1a (77 participants in total) and one of methotrexate (60
      participants). None of these trials showed significant benefit in the primary
      outcome or secondary outcomes selected for this review. AUTHORS' CONCLUSIONS: The
      evidence from randomised trials does not show significant benefit from
      azathioprine, interferon beta-1a or methotrexate but none of the trials was large
      enough to rule out small or moderate benefit. The evidence from observational
      studies is insufficient to avoid the need for randomised controlled trials to
      discover whether these drugs are beneficial. Future trials should have improved
      designs, more sensitive outcome measures and longer durations.

PMID- 21069675
TI  - Addition of drug/s to a chemotherapy regimen for metastatic breast cancer.
AB  - BACKGROUND: The addition of a chemotherapy drug or drugs to an established
      regimen is one method used to increase the dose and intensity of treatment for
      metastatic breast cancer. OBJECTIVES: To assess the effects of adding one or more
      chemotherapy drugs to an established regimen in women with metastatic breast
      cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group's
      Specialised Register (to August 2009) using the codes for "advanced breast
      cancer" and "chemotherapy". This review is an update of the original Cochrane
      Review (Issue 3, 2006). SELECTION CRITERIA: Randomised trials with a first line
      regimen of at least two chemotherapy drugs compared to the same regimen plus the
      addition of one or more chemotherapy drugs in women with metastatic breast
      cancer. DATA COLLECTION AND ANALYSIS: Two authors extracted data independently
      from published trials. We derived hazard ratios (HR) from time-to-event outcomes
      where possible, and used a fixed-effect model for meta-analysis. We analysed
      response rates as dichotomous variables and extracted toxicity data where
      available. MAIN RESULTS: We identified 17 trials reporting on 22 treatment
      comparisons (2674 patients randomised). Fifteen trials (20 treatment comparisons)
      reported results for tumour response and 11 trials (14 treatment comparisons)
      published time-to-event data for overall survival. There were 1532 deaths in 2116
      women randomised to trials of the addition of a drug to the regimen and control
      (the regimen alone). There was no detectable difference in overall survival
      between these patients, with an overall HR of 0.96 (95% confidence interval (CI)
      0.87 to 1.07, P = 0.47) and no significant heterogeneity. We found no difference
      in time to progression between these regimens, with an overall HR of 0.93 (95% CI
      0.81 to 1.07, P = 0.31) and no significant heterogeneity. Addition of a drug to
      the regimen was favourably associated with overall tumour response rates (odds
      ratio 1.21, 95% CI 1.01 to 1.44, P = 0.04) although we observed significant
      heterogeneity for this outcome across the trials. Where measured, acute
      toxicities such as alopecia, nausea and vomiting and leucopenia were more common
      with the addition of a drug. AUTHORS' CONCLUSIONS: The addition of one or more
      drugs to the regimen shows a statistically significant advantage for tumour
      response in women with metastatic breast cancer but the results suggest no
      difference in survival time or time to progression. The positive effect on tumour
      response was also associated with increased toxicity.

PMID- 21069676
TI  - Interventions for idiopathic steroid-resistant nephrotic syndrome in children.
AB  - BACKGROUND: The majority of children who present with their first episode of
      nephrotic syndrome achieve remission with corticosteroid therapy. Children who
      fail to respond may be treated with immunosuppressive agents including
      calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive
      agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal
      combinations of these agents with the least toxicity remain to be determined.
      OBJECTIVES: To evaluate the benefits and harms of interventions used to treat
      idiopathic steroid-resistant nephrotic syndrome (SRNS) in children. SEARCH
      STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane
      Renal Group's specialised register, Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. SELECTION
      CRITERIA: RCTs and quasi-RCTs were included if they compared different
      immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone
      or other agent given orally or parenterally in children aged three months to 18
      years with SRNS. DATA COLLECTION AND ANALYSIS: Two authors independently searched
      the literature, determined study eligibility, assessed quality and extracted
      data. For dichotomous outcomes, results were expressed as risk ratios (RR) and
      95% confidence intervals (CI). Data were pooled using the random effects model.
      MAIN RESULTS: Fourteen RCTs (449 children) were included. Cyclosporin when
      compared with placebo or no treatment significantly increased the number of
      children who achieved complete remission (three studies, 49 children: RR 7.66,
      95% CI 1.06 to 55.34). Cyclosporin significantly increased the number with
      complete or partial remission compared with IV cyclophosphamide (one study, 32
      children: RR 3.40, 95% CI 1.12 to 10.28). There was no significant difference in
      the number who achieved complete remission between oral cyclophosphamide with
      prednisone versus prednisone alone (two studies, 91 children: RR 1.06, 95% CI
      0.61 to 1.87), IV versus oral cyclophosphamide (one study, 11 children: RR 3.13,
      95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide with IV
      dexamethasone (one study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), tacrolimus
      versus cyclosporin (one study, 41 children: RR 0.86, 95% CI 0.44 to 1.66) and
      azathioprine with prednisone versus prednisone alone (one study, 31 children: RR
      0.94, 95% CI 0.15 to 5.84). ACEi significantly reduced proteinuria (two studies,
      70 children). No studies were identified comparing high dose steroids and
      cyclosporin with single agents, placebo or no treatment. AUTHORS' CONCLUSIONS:
      Further adequately powered, well designed RCTs are needed to confirm the efficacy
      of cyclosporin and to evaluate other regimens for idiopathic SRNS including high
      dose steroids with cyclosporin.

PMID- 21069677
TI  - Volume-targeted versus pressure-limited ventilation in the neonate.
AB  - BACKGROUND: Damage caused by lung overdistension (volutrauma) has been implicated
      in the development bronchopulmonary dysplasia (BPD). Modern neonatal ventilation
      modes can target a set tidal volume as an alternative to traditional pressure
      limited ventilation using a fixed inflation pressure. Volume targeting aims to
      produce a more stable tidal volume in order to reduce lung damage and stabilise
      pCO(2) OBJECTIVES: To determine whether volume-targeted ventilation (VTV)
      compared with pressure-limited ventilation (PLV) leads to reduced rates of death
      and BPD in newborn infants. Secondary objectives were to determine whether use of
      VTV affected outcomes including air leak, cranial ultrasound findings and
      neurodevelopment. SEARCH STRATEGY: The search strategy comprised searches of the
      Cochrane Central Register of Controlled Trials, MEDLINE PubMed 1966 to January
      2010, and hand searches of reference lists of relevant articles and conference
      proceedings. SELECTION CRITERIA: All randomised and quasi-randomised trials
      comparing the use of volume-targeted versus pressure-limited ventilation in
      infants of less than 28 days corrected age. DATA COLLECTION AND ANALYSIS: Two
      review authors assessed the methodological quality of eligible trials and
      extracted data independently. When appropriate, meta-analysis was conducted to
      provide a pooled estimate of effect. For categorical data the relative risk (RR)
      and risk difference (RD) were calculated with 95% confidence intervals. Number
      needed to treat was calculated when RD was statistically significant. Continuous
      data were analysed using weighted mean difference. MAIN RESULTS: Twelve
      randomised trials met our inclusion criteria; nine parallel trials (629 infants)
      and three crossover trials (64 infants).The use of VTV modes resulted in a
      reduction in the combined outcome of death or bronchopulmonary dysplasia [typical
      RR 0.73 (95% CI 0.57 to 0.93), NNT8 (95% CI 5 to 33)]. VTV modes also resulted in
      reductions in pneumothorax [typical RR 0.46 (95% CI 0.25 to 0.84), NNT 17 (95% CI
      10 to 100)], days of ventilation [MD -2.36 (95% CI -3.9 to -0.8)], hypocarbia
      [typical RR 0.56 (95%CI 0.33 to 0.96), NNT 4 (95% CI 2 to 25)] and the combined
      outcome of periventricular leukomalacia or grade 3-4 intraventricular haemorrhage
      [typical RR 0.48 (95% CI 0.28 to 0.84), NNT 11 (95% CI 7 to 50)]. AUTHORS'
      CONCLUSIONS: Infants ventilated using VTV modes had reduced death and chronic
      lung disease compared with infants ventilated using PLV modes. Further studies
      are needed to identify whether VTV modes improve neurodevelopmental outcomes and
      to compare and refine VTV strategies.

PMID- 21069678
TI  - Fraction size in radiation treatment for breast conservation in early breast
      cancer.
AB  - BACKGROUND: Shortening the duration of radiation therapy would benefit women with
      early breast cancer treated with breast conserving surgery. It may also improve
      access to radiation therapy by improving efficiency in radiation oncology
      departments globally. This can only happen if the shorter treatment is as
      effective and safe as conventional radiation therapy. This is an updated version
      of the original Cochrane Review published in Issue 3, 2008. OBJECTIVES: To
      determine the effect of altered radiation fraction size on outcomes for women
      with early breast cancer who have undergone breast conserving surgery. SEARCH
      STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register,
      MEDLINE, EMBASE and the WHO ICTRP search portal to June 2009, reference lists of
      articles and relevant conference proceedings. We applied no language constraints.
      SELECTION CRITERIA: Randomised controlled trials of unconventional versus
      conventional fractionation in women with early breast cancer who had undergone
      breast conserving surgery. DATA COLLECTION AND ANALYSIS: The authors performed
      data extraction independently, with disagreements resolved by discussion. We
      sought missing data from trial authors. MAIN RESULTS: Four trials reported on
      7095 women. The women were highly selected: tumours were node negative and 89.8%
      were smaller than 3 cm. Where the breast size was known, 87% had small or medium
      breasts. The studies were of low to medium quality. Unconventional fractionation
      (delivering radiation therapy in larger amounts each day but over fewer days than
      with conventional fractionation) did not affect: (1) local recurrence risk ratio
      (RR) 0.97 (95% CI 0.76 to 1.22, P = 0.78), (2) breast appearance RR 1.17 (95% CI
      0.98 to 1.39, P = 0.09), (3) survival at five years RR 0.89 (95% CI 0.77 to 1.04,
      P = 0.16). Acute skin toxicity was decreased with unconventional fractionation:
      RR 0.21 (95% CI 0.07 to 0.64, P = 0.007). AUTHORS' CONCLUSIONS: Two new studies
      have been published since the last version of the review, altering our
      conclusions. We have evidence from four low to medium quality randomised trials
      that using unconventional fractionation regimens (greater than 2 Gy per fraction)
      does not affect local recurrence, is associated with decreased acute toxicity and
      does not seem to affect breast appearance or late toxicity for selected women
      treated with breast conserving therapy. These are mostly women with node negative
      tumours smaller than 3 cm and negative pathological margins. Long-term follow up
      (> 5 years) is available for a small proportion of the patients randomised.
      Longer follow up is required for a more complete assessment of the effect of
      altered fractionation.

PMID- 21069679
TI  - Interventions for the prevention and management of oropharyngeal candidiasis
      associated with HIV infection in adults and children.
AB  - BACKGROUND: Oral candidiasis (OC) associated with human immunodeficiency virus
      (HIV) infection occurs commonly and recurs frequently, often presenting as an
      initial manifestation of the disease. Left untreated, these lesions contribute
      considerably to the morbidity associated with HIV infection. Interventions aimed
      at preventing and treating HIV-associated oral candidal lesions form an integral
      component of maintaining the quality of life for affected individuals.
      OBJECTIVES: To determine the effects of any intervention in preventing or
      treating OC in children and adults with HIV infection. SEARCH STRATEGY: The
      search strategy was based on that of the Cochrane HIV/AIDS Review Group. The
      following electronic databases were searched for randomised controlled trials for
      the years 1982 to 2005: Medline, AIDSearch, EMBASE and CINAHL. The Cochrane
      Database of Systematic Reviews, Database of Abstracts of Reviews of
      Effectiveness, and the Cochrane Central Register of Controlled Trials (CENTRAL)
      were also searched through May 2005. The abstracts of relevant conferences,
      including the International Conferences on AIDS and the Conference on
      Retroviruses and Opportunistic Infections, as indexed by AIDSLINE, were also
      reviewed. The strategy was iterative, in that references of included studies were
      searched for additional references. All languages were included.The updated
      database search was done for the period 2005 up to 2009. The following databases
      were searched: Medline, EMBASE, the Cochrane Database of Systematic Reviews,
      Database of Abstracts of Reviews of Effectiveness and the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library. AIDSearch was
      not searched for the updated search as it ceased publication during 2008.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of palliative,
      preventative or curative therapy were considered, irrespective of whether the
      control group received a placebo. Participants were HIV positive adults and
      children. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the
      methodological quality of the trials and extracted data. Study authors were
      contacted for additional data where necessary. MAIN RESULTS: For the first
      publication of the review in 2006, forty studies were retrieved. Twenty eight
      trials (n=3225) met inclusion criteria. During the update search for the review
      a, further six studies were identified. Of these, five met the inclusion criteria
      and were included in the review. The review now includes 33 studies (n=3445): 22
      assessing treatment and 11 assessing prevention of oropharyngeal candidiasis. Six
      studies were done in developing countries, 16 in the United States of America and
      the remainder in Europe.Treatment Treatment was assessed in the majority of
      trials looking at both clinical and mycological cures. In the majority of
      comparisons there was only one trial. Compared to nystatin, fluconazole favoured
      clinical cure in adults (1 RCT; n=167; RR 1.69; 95% CI 1.27 to 2.23). There was
      no difference with regard to clinical cure between fluconazole compared to
      ketoconazole (2 RCTs; n=83; RR 1.27; 95% CI 0.97 to 1.66), itraconazole (2 RCTs;
      n=434; RR 1.05; 95% CI 0.94 to 1.16), clotrimazole (2 RCTs; n=358; RR 1.14; 95%
      CI 0.92 to 1.42) or posaconazole (1 RCT; n=366; RR1.32; 95% CI 0.36 to 4.83). Two
      trials compared different dosages of fluconazole with no difference in clinical
      cure. When compared with clotrimazole, both fluconazole (2 RCTs; n=358; RR 1.47;
      95% CI 1.16 to 1.87) and itraconazole (1 RCT; n=123; RR 2.20; 95% CI 1.43 to3.39)
      proved to be better for mycological cure. Both gentian violet (1 RCT; n=96; RR
      5.28; 95% CI 1.23 to 22.55) and ketoconazole (1 RCT; n=92; RR 5.22; 95% CI 1.21
      to 22.53) were superior to nystatin in bringing about clinical cure. A single
      trial compared gentian violet with lemon juice and lemon grass with no
      significant difference in clinical cure between the groups. Prevention Successful
      prevention was defined as the prevention of a relapse while receiving
      prophylaxis. Fluconazole was compared with placebo in five studies (5 RCTs;
      n=599; RR 0.61; 95% CI 0.5 to 0.74) and with no treatment in another (1 RCT;
      n=65; RR 0.16; 95% CI 0.08 to 0.34). In both instances the prevention of clinical
      episodes was favoured by fluconazole. Comparing continuous fluconazole treatment
      with intermittent treatment (2 RCTs; n=891; RR 0.65; 95% CI 0.23 to 1.83), there
      was no significant difference between the two treatment arms. Chlorhexidine was
      compared with normal saline in a single study with no significant difference
      between the treatment arms. AUTHORS' CONCLUSIONS: Five new studies were added to
      the review, but their results do not alter the final conclusion of the
      review.Implications for practice Due to there being only one study in children,
      it is not possible to make recommendations for treatment or prevention of OC in
      children. Amongst adults, there were few studies per comparison. Due to
      insufficient evidence, no conclusion could be made about the effectiveness of
      clotrimazole, nystatin, amphotericin B, itraconazole or ketoconazole with regard
      to OC prophylaxis. In comparison to placebo, fluconazole is an effective
      preventative intervention. However, the potential for resistant Candida organisms
      to develop, as well as the cost of prophylaxis, might impact the feasibility of
      implementation. No studies were found comparing fluconazole with other
      interventions. The direction of findings suggests that ketoconazole, fluconazole,
      itraconazole and clotrimazole improved the treatment outcomes.Implications for
      research It is encouraging that low-cost alternatives are being tested, but more
      research needs to be on in this area and on interventions like gentian violet and
      other less expensive anti-fungal drugs to treat OC. More well-designed treatment
      trials with larger samples are needed to allow for sufficient power to detect
      differences in not only clinical, but also mycological, response and relapse
      rates. There is also a strong need for more research to be done on the treatment
      and prevention of OC in children as it is reported that OC is the most frequent
      fungal infection in children and adolescents who are HIV positive. More research
      on the effectiveness of less expensive interventions also needs to be done in
      resource-poor settings. Currently few trials report outcomes related to quality
      of life, nutrition, or survival. Future researchers should consider measuring
      these when planning trials. Development of resistance remains under-studied and
      more work must be done in this area. It is recommended that trials be more
      standardised and conform more closely to CONSORT.

PMID- 21069680
TI  - Screening programmes for the early detection and prevention of oral cancer.
AB  - BACKGROUND: Oral cancer is an important global healthcare problem, its incidence
      is increasing and late-stage presentation is common. Screening programmes have
      been introduced for a number of major cancers and have proved effective in their
      early detection. Given the high morbidity and mortality rates associated with
      oral cancer, there is a need to determine the effectiveness of a screening
      programme for this disease, either as a targeted, opportunistic or population
      based measure. Evidence exists from modelled data that a visual oral examination
      of high-risk individuals may be a cost-effective screening strategy and the
      development and use of adjunctive aids and biomarkers is becoming increasingly
      common. OBJECTIVES: To assess the effectiveness of current screening methods in
      decreasing oral cancer mortality. SEARCH STRATEGY: The following electronic
      databases were searched: the Cochrane Oral Health Group Trials Register (to 20
      May 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2010, Issue 2), MEDLINE via OVID (1950 to 20 May 2010), EMBASE
      via OVID (1980 to 20 May 2010) and CANCERLIT via PubMed (1950 to 20 May 2010).
      There were no restrictions regarding language or date of publication. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) of screening for oral cancer or
      potentially malignant disorders using visual examination, toluidine blue,
      fluorescence imaging or brush biopsy. DATA COLLECTION AND ANALYSIS: The original
      review identified 1389 citations and this update identified an additional 330
      studies, highlighting 1719 studies for consideration. Only one study met the
      inclusion criteria and validity assessment, data extraction and statistics
      evaluation were undertaken by six independent review authors. MAIN RESULTS: One 9
      year RCT has been included (n = 13 clusters: 191,873 participants). There was no
      statistically significant difference in the age-standardised oral cancer
      mortality rates for the screened group (16.4/100,000 person-years) and the
      control group (20.7/100,000 person-years). A 43% reduction in mortality was
      reported between the intervention cohort (29.9/100,000 person-years) and the
      control arm (45.4/100,000) for high-risk individuals who used tobacco or alcohol
      or both, which was statistically significant. However, this study had a number of
      methodological weaknesses and the associated risk of bias was high. AUTHORS'
      CONCLUSIONS: Although there is evidence that a visual examination as part of a
      population based screening programme reduced the mortality rate of oral cancer in
      high-risk individuals, whilst producing a stage shift and improvement in survival
      rates across the population as a whole, the evidence is limited to one study and
      is associated with a high risk of bias. This was compounded by the fact that the
      effect of cluster randomisation was not accounted for in the analysis.
      Furthermore, no robust evidence was identified to support the use of other
      adjunctive technologies like toluidine blue, brush biopsy or fluorescence imaging
      within a primary care environment. Further randomised controlled trials are
      recommended to assess the efficacy, effectiveness and cost-effectiveness of a
      visual examination as part of a population based screening programme.

PMID- 21069681
TI  - Stage-based interventions for smoking cessation.
AB  - BACKGROUND: The transtheoretical model is the most widely known of several stage
      based theories of behaviour. It proposes that smokers move through a discrete
      series of motivational stages before they quit successfully. These are
      precontemplation (no thoughts of quitting), contemplation (thinking about
      quitting), preparation (planning to quit in the next 30 days), action (quitting
      successfully for up to six months), and maintenance (no smoking for more than six
      months). According to this influential model, interventions which help people to
      stop smoking should be tailored to their stage of readiness to quit, and are
      designed to move them forward through subsequent stages to eventual success.
      People in the preparation and action stages of quitting would require different
      types of support from those in precontemplation or contemplation. OBJECTIVES: Our
      primary objective was to test the effectiveness of stage-based interventions in
      helping smokers to quit. SEARCH STRATEGY: We searched the Cochrane Tobacco
      Addiction Group's specialised register for trials, using the terms ('stage* of
      change', 'transtheoretical model*', 'trans-theoretical model*, 'precaution
      adoption model*', 'health action model', 'processes of change questionnaire*',
      'readiness to change', 'tailor*') and 'smoking' in the title or abstract, or as
      keywords. The latest search was in August 2010. SELECTION CRITERIA: We included
      randomized controlled trials, which compared stage-based interventions with non
      stage-based controls, with 'usual care' or with assessment only. We excluded
      trials which did not report a minimum follow-up period of six months from start
      of treatment, and those which measured stage of change but did not modify their
      intervention in the light of it. DATA COLLECTION AND ANALYSIS: We extracted data
      in duplicate on the participants, the dose and duration of intervention, the
      outcome measures, the randomization procedure, concealment of allocation, and
      completeness of follow up.The main outcome was abstinence from smoking for at
      least six months. We used the most rigorous definition of abstinence, and
      preferred biochemically validated rates where reported. Where appropriate we
      performed meta-analysis to estimate a pooled risk ratio, using the Mantel
      Haenszel fixed-effect model. MAIN RESULTS: We found 41 trials (>33,000
      participants) which met our inclusion criteria. Four trials, which directly
      compared the same intervention in stage-based and standard versions, found no
      clear advantage for the staging component. Stage-based versus standard self-help
      materials (two trials) gave a relative risk (RR) of 0.93 (95% CI 0.62 to 1.39).
      Stage-based versus standard counselling (two trials) gave a relative risk of 1.00
      (95% CI 0.82 to 1.22). Six trials of stage-based self-help systems versus any
      standard self-help support demonstrated a benefit for the staged groups, with an
      RR of 1.27 (95% CI 1.01 to 1.59). Twelve trials comparing stage-based self help
      with 'usual care' or assessment-only gave an RR of 1.32 (95% CI 1.17 to 1.48).
      Thirteen trials of stage-based individual counselling versus any control
      condition gave an RR of 1.24 (95% CI 1.08 to 1.42). These findings are consistent
      with the proven effectiveness of these interventions in their non-stage-based
      versions. The evidence was unclear for telephone counselling, interactive
      computer programmes or training of doctors or lay supporters. This uncertainty
      may be due in part to smaller numbers of trials. AUTHORS' CONCLUSIONS: Based on
      four trials using direct comparisons, stage-based self-help interventions (expert
      systems and/or tailored materials) and individual counselling were neither more
      nor less effective than their non-stage-based equivalents. Thirty-one trials of
      stage-based self help or counselling interventions versus any control condition
      demonstrated levels of effectiveness which were comparable with their non-stage
      based counterparts. Providing these forms of practical support to those trying to
      quit appears to be more productive than not intervening. However, the additional
      value of adapting the intervention to the smoker's stage of change is uncertain.
      The evidence is not clear for other types of staged intervention, including
      telephone counselling, interactive computer programmes and training of physicians
      or lay supporters. The evidence does not support the restriction of quitting
      advice and encouragement only to those smokers perceived to be in the preparation
      and action stages.

PMID- 21069682
TI  - Speed cameras for the prevention of road traffic injuries and deaths.
AB  - BACKGROUND: It is estimated that by 2020, road traffic crashes will have moved
      from ninth to third in the world ranking of burden of disease, as measured in
      disability adjusted life years. The prevention of road traffic injuries is of
      global public health importance. Measures aimed at reducing traffic speed are
      considered essential to preventing road injuries; the use of speed cameras is one
      such measure. OBJECTIVES: To assess whether the use of speed cameras reduces the
      incidence of speeding, road traffic crashes, injuries and deaths. SEARCH
      STRATEGY: We searched the following electronic databases covering all available
      years up to March 2010; the Cochrane Library, MEDLINE (WebSPIRS), EMBASE
      (WebSPIRS), TRANSPORT, IRRD (International Road Research Documentation), TRANSDOC
      (European Conference of Ministers of Transport databases), Web of Science
      (Science and Social Science Citation Index), PsycINFO, CINAHL, EconLit, WHO
      database, Sociological Abstracts, Dissertation Abstracts, Index to Theses.
      SELECTION CRITERIA: Randomised controlled trials, interrupted time series and
      controlled before-after studies that assessed the impact of speed cameras on
      speeding, road crashes, crashes causing injury and fatalities were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: We independently screened studies for
      inclusion, extracted data, assessed methodological quality, reported study
      authors' outcomes and where possible, calculated standardised results based on
      the information available in each study. Due to considerable heterogeneity
      between and within included studies, a meta-analysis was not appropriate. MAIN
      RESULTS: Thirty five studies met the inclusion criteria. Compared with controls,
      the relative reduction in average speed ranged from 1% to 15% and the reduction
      in proportion of vehicles speeding ranged from 14% to 65%. In the vicinity of
      camera sites, the pre/post reductions ranged from 8% to 49% for all crashes and
      11% to 44% for fatal and serious injury crashes. Compared with controls, the
      relative improvement in pre/post injury crash proportions ranged from 8% to 50%.
      AUTHORS' CONCLUSIONS: Despite the methodological limitations and the variability
      in degree of signal to noise effect, the consistency of reported reductions in
      speed and crash outcomes across all studies show that speed cameras are a
      worthwhile intervention for reducing the number of road traffic injuries and
      deaths. However, whilst the the evidence base clearly demonstrates a positive
      direction in the effect, an overall magnitude of this effect is currently not
      deducible due to heterogeneity and lack of methodological rigour. More studies of
      a scientifically rigorous and homogenous nature are necessary, to provide the
      answer to the magnitude of effect.

PMID- 21069683
TI  - Recombinant human interleukin 10 for induction of remission in Crohn's disease.
AB  - BACKGROUND: The etiology of Crohn's disease remains unknown, nevertheless, it is
      apparent that inflammation is associated with an imbalance between
      proinflammatory and anti-inflammatory cytokines produced within the intestinal
      mucosa. Crohn's disease represents a state of dysregulated inflammation and drugs
      that can augment the anti-inflammatory response have the potential to
      downregulate inflammation and thereby improve the disease. The efficacy of
      recombinant IL-10 in Crohn's disease was first demonstrated in a pilot study.
      Since then other trials have evaluated its efficacy but the available evidence
      has not been systematically reviewed. OBJECTIVES: To determine the efficacy and
      tolerability of recombinant human interleukin 10 (IL-10) for induction of
      remission in Crohn's disease. SEARCH STRATEGY: A computer assisted search of the
      Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Review
      Group Specialized Trials Register and the on-line databases MEDLINE and EMBASE
      was performed to identify relevant publications up to September 2010. Reference
      lists were searched and the pharmaceutical industry and experts were contacted to
      identify additional studies. SELECTION CRITERIA: Randomized controlled trials
      comparing recombinant human interleukin 10 to a placebo or control therapy for
      the treatment of patients with active Crohn's disease were included. DATA
      COLLECTION AND ANALYSIS: All publications identified by the search strategy were
      assessed independently by two authors, and relevant studies selected according to
      the inclusion criteria. The risk of bias of each included study was assessed
      independently by two authors. Data were analyzed using Review Manager (RevMan 5).
      A random effects model was used for pooling of data. All data were analyzed on an
      intention-to-treat basis. Heterogeneity among studies was assessed using the chi
      square test and the I(2) statistic. MAIN RESULTS: The risk of bias in the
      included studies was low. The overall quality of the evidence based on the GRADE
      approach was moderate. No statistically significant differences were found
      between interleukin 10 and placebo for complete remission (CDAI < 150 with a 100
      point decrease in CDAI from baseline; RR=1.43; 95% CI 0.62 to 3.29; I(2)=40%) or
      clinical remission (CDAI < 150; RR=1.29; 95% CI 0.79 to 2.11; I(2)= 0%). Patients
      treated with interleukin 10 were significantly more likely to withdraw from the
      studies due to adverse events (RR=13.50; 95% CI 3.89 to 46.79; I(2)=0%). AUTHORS'
      CONCLUSIONS: Interleukin 10 does not appear to provide any benefit for the
      treatment of active Crohn's disease. This systematic review shows that
      interleukin 10 does not increase the number of remissions (complete or clinical),
      but increases the rate of withdrawal due to adverse events relative to placebo.
      The quality of the evidence regarding the efficacy of IL-10 is moderate and
      although further research may have an impact on point estimates of efficacy
      further randomized trials are unlikely to be undertaken.

PMID- 21069684
TI  - Antibiotic prophylaxis for third- and fourth-degree perineal tear during vaginal
      birth.
AB  - BACKGROUND: One to eight per cent of women suffer third-degree perineal tear
      (anal sphincter injury) and fourth-degree perineal tear (rectal mucosa injury)
      during vaginal birth, and these tears are more common after forceps delivery
      (28%) and midline episiotomies. Third- and fourth-degree tears can become
      contaminated with bacteria from the rectum and this significantly increases in
      the chance of perineal wound infection. Prophylactic antibiotics might have a
      role in preventing this infection. OBJECTIVES: To assess the effectiveness of
      antibiotic prophylaxis for reducing maternal morbidity and side effects in third-
      and fourth-degree perineal tear during vaginal birth. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August
      2010) and the reference lists of retrieved articles. SELECTION CRITERIA:
      Randomised controlled trials comparing outcomes of prophylactic antibiotics
      versus placebo or no antibiotics in third- and fourth-degree perineal tear during
      vaginal birth. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the reports and extracted data. MAIN RESULTS: We identified and included
      one trial (147 participants) that compared the effect of prophylactic antibiotic
      (single-dose, second generation cephalosporin, intravenously) on postpartum
      perineal wound complications in third- or fourth-degree perineal tears. Perineal
      wound complications (wound disruption and purulent discharge) at the two-week
      postpartum check up were 8.20% and 24.10% in the treatment and the control groups
      respectively (risk ratio 0.34, 95% confidence interval 0.12 to 0.96). AUTHORS'
      CONCLUSIONS: Although the data suggest that prophylactic antibiotics help to
      prevent perineal wound complications following third- or fourth-degree perineal
      tear, loss to follow-up was very high. The results should be interpreted with
      caution as they are based on one small trial.

PMID- 21069685
TI  - Anti-pseudomonal beta-lactams for the initial, empirical, treatment of febrile
      neutropenia: comparison of beta-lactams.
AB  - BACKGROUND: Several beta-lactams are recommended as single agents for the
      treatment of febrile neutropenia. OBJECTIVES: To compare the effectiveness of
      different anti-pseudomonal beta-lactams as single agents in the treatment of
      febrile neutropenia. To compare the development of bacterial resistance,
      bacterial and fungal superinfections during or following treatment with the
      different beta-lactams. SEARCH STRATEGY: We searched the Cochane Register of
      Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug
      applications, conference proceedings and ongoing clinical trial databases up to
      August 2010. References of included studies were scanned. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to
      another antipseudomonal beta-lactam antibiotic, both given alone or with the
      addition of the same glycopeptide to both study arms, for the initial treatment
      of fever and neutropenia among cancer patients. DATA COLLECTION AND ANALYSIS: Two
      review authors applied inclusion criteria and extracted the data independently.
      Missing data were sought. Risk ratios (RR) were calculated with 95% confidence
      intervals (CI), and pooled using the fixed effect model. The primary outcome was
      all-cause mortality. Risk of bias was assessed using a domain-based evaluation
      and its effect of results was assessed through sensitivity analyses. MAIN
      RESULTS: Forty-four trials were included. The antibiotics assessed were cefepime,
      ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation
      concealment and generation were reported in about half of the trials and only two
      trials were double-blinded. The risk for all-cause mortality was significantly
      higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to
      1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in
      trials at low risk for bias. There were no differences in secondary outcomes but
      for a non-significantly higher rate of bacterial superinfections with cefepime.
      Mortality was significantly lower with piperacillin-tazobactam compared to other
      antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without
      heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower
      rate of clinical failure and antibiotic modifications as compared to other
      antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.
      AUTHORS' CONCLUSIONS: Current evidence supports the use of piperacillin
      tazobactam in locations where antibiotic resistance profiles do not mandate
      empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic
      associated and Clostridium difficile-associated diarrhea. There is a high level
      of evidence that all-cause mortality is higher with cefepime compared to other
      beta-lactams and it should not be used as monotherapy for patients with febrile
      neutropenia.

PMID- 21069686
TI  - Choice of instruments for assisted vaginal delivery.
AB  - BACKGROUND: Instrumental or assisted vaginal birth is commonly used to expedite
      birth for the benefit of either mother or baby or both. It is sometimes
      associated with significant complications for both mother and baby. The choice of
      instrument may be influenced by clinical circumstances, operator choice and
      availability of specific instruments. OBJECTIVES: To evaluate different
      instruments in terms of achieving a vaginal birth and avoiding significant
      morbidity for mother and baby. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (31 May 2010). SELECTION
      CRITERIA: Randomised controlled trials of assisted vaginal delivery using
      different instruments. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality, extracted the data, and checked them for
      accuracy. MAIN RESULTS: We included 32 studies (6597 women) in this review.
      Forceps were less likely than the ventouse to fail to achieve a vaginal birth
      with the allocated instrument (risk ratio (RR) 0.65, 95% confidence interval (CI)
      0.45 to 0.94). However, with forceps there was a trend to more caesarean
      sections, and significantly more third- or fourth-degree tears (with or without
      episiotomy), vaginal trauma, use of general anaesthesia, and flatus incontinence
      or altered continence. Facial injury was more likely with forceps (RR 5.10, 95%
      CI 1.12 to 23.25). Using a random-effects model because of heterogeneity between
      studies, there was a trend towards fewer cases of cephalhaematoma with forceps
      (average RR 0.64, 95% CI 0.37 to 1.11).Among different types of ventouse, the
      metal cup was more likely to result in a successful vaginal birth than the soft
      cup, with more cases of scalp injury and cephalhaematoma. The hand-held ventouse
      was associated with more failures than the metal ventouse, and a trend to fewer
      than the soft ventouse.Overall forceps or the metal cup appear to be most
      effective at achieving a vaginal birth, but with increased risk of maternal
      trauma with forceps and neonatal trauma with the metal cup. AUTHORS' CONCLUSIONS:
      There is a recognised place for forceps and all types of ventouse in clinical
      practice. The role of operator training with any choice of instrument must be
      emphasised. The increasing risks of failed delivery with the chosen instrument
      from forceps to metal cup to hand-held to soft cup vacuum, and trade-offs between
      risks of maternal and neonatal trauma identified in this review need to be
      considered when choosing an instrument.

PMID- 21069687
TI  - Soft versus firm catheters for intrauterine insemination.
AB  - BACKGROUND: Intrauterine insemination (IUI) is a recommended treatment for
      unexplained subfertility. The treatment involves the direct delivery of
      spermatozoa into the uterus using a catheter. Many factors influence the success
      of IUI treatments including the type of catheter used. OBJECTIVES: To compare
      pregnancy-related outcomes from women undergoing intrauterine insemination cycles
      performed with either soft or firm catheters in subfertile women. SEARCH
      STRATEGY: We searched the following databases (inception to July 2010) with no
      language restrictions: Cochrane Menstrual Disorders and Subfertility Group
      Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PsycINFO,
      CINAHL, LILACS and OpenSigle. We also searched the conference abstracts in the
      ISI Web of Knowledge and Google, and conference abstracts and citation lists of
      relevant publications, reviews and included studies. SELECTION CRITERIA: We
      included only truly randomised controlled studies of women who underwent IUI
      using either soft or firm catheter types and reporting data on rates of live
      birth, clinical pregnancy, multiple pregnancy, miscarriage, ease of introduction
      of the catheter, occurrence of trauma, or woman's discomfort. DATA COLLECTION AND
      ANALYSIS: Two review authors screened the titles and abstracts of 78 potentially
      eligible studies and excluded 66 of these. We critically appraised the full texts
      of twelve studies and excluded three studies. Nine publications of six studies
      were remaining. We extracted data from the six remaining studies and there were
      no disagreements. We assessed risk of bias and pooled dichotomous data and
      presented the Peto odds ratios (OR) with 95% confidence intervals (CI). MAIN
      RESULTS: There was no evidence of a significant effect difference regarding the
      choice of catheter type for any of the outcomes. Three studies reported live
      birth rates (OR 0.94, 95% CI 0.65 to 1.35) with a translated OR percentages (1.3,
      95% CI 0.56 to 3.1) while six studies reported clinical pregnancy rates (OR 1.0,
      95% CI 0.73 to 1.35 ). Two studies were pooled for the analysis of miscarriages
      (OR 1.25, 95% CI 0.49 to 3.22). Results of other adverse outcomes were reported
      per cycle and were therefore not pooled. AUTHORS' CONCLUSIONS: On the basis of
      the evidence available in this review, no specific conclusion can be made
      regarding the superiority of one catheter class over another. Further adequately
      powered studies reporting on clinical outcomes (e.g. live birth rate) are
      required. Additional outcomes such as miscarriage rates and measures of
      discomfort need to be reported.

PMID- 21069688
TI  - Provision of a surgeon's performance data for people considering elective
      surgery.
AB  - BACKGROUND: A consumer model of health supports that elective surgery patients
      should be informed about the past operative performance of their surgeon before
      making two important decisions: 1) to consent to the proposed surgery, and 2) to
      have a particular doctor perform the surgery. This information arguably helps
      empower patients to participate in their care. While surgeons' performance data
      are available in some settings there continues to be controversy over the
      provision of such data to patients, and the question of whether consumers should,
      or want to, be provided with this information. OBJECTIVES: To assess the effects
      of providing a surgeon's performance data to people considering elective surgery.
      SEARCH STRATEGY: We searched the following databases: Cochrane Central Register
      of Controlled Trials (CENTRAL, The Cochrane Library, 20 Oct 2009); MEDLINE (Ovid)
      (28 Sep 2009); EMBASE (Ovid) (28 Sep 2009); PsycINFO (Ovid) (28 Sep 2009); CINAHL
      (Ebsco) (20 Oct 2009), Current Contents (Ovid) (23 Nov 2009), and Proquest
      Dissertations and Theses (20 October 2009). We searched all databases from their
      start dates. SELECTION CRITERIA: Randomised and cluster randomised controlled
      trials (RCTs), quasi-RCTs and controlled before and after studies, in which an
      individual surgeon's performance data were provided to patients considering
      elective surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the titles and abstracts of retrieved citations. No studies were
      identified for inclusion. Consequently, no data collection or analysis was
      conducted. MAIN RESULTS: We found no studies that met the inclusion criteria,
      therefore there are no results to report on the effect of the provision of a
      surgeon's performance data for people considering elective surgery. AUTHORS'
      CONCLUSIONS: We found no studies reporting the impact of the provision of a
      surgeon's performance data for people considering elective surgery. This is an
      important finding in itself. While the public reporting of a surgeon's
      performance is not a new concept, the efficacy of this data for individual
      patients has not been empirically tested. We recommend that a review of
      qualitative studies or new primary qualitative research be conducted to determine
      what interventions are currently in use and explore the attitudes of consumers
      and professionals towards such interventions.

PMID- 21069689
TI  - Radical prostatectomy versus watchful waiting for prostate cancer.
AB  - BACKGROUND: The lack of evidence regarding the effectiveness of treatment options
      for clinically localised prostate cancer continues to impact on clinical decision
      making. Two such options are radical prostatectomy (RP) and watchful waiting
      (WW). WW involves providing no initial treatment and monitoring the patient with
      the intention of providing palliative treatment if there is evidence of disease
      progression. OBJECTIVES: To compare the beneficial and harmful effects of RP
      versus WW for the treatment of localised prostate cancer. SEARCH STRATEGY:
      MEDLINE, EMBASE, The Cochrane Library, ISI Science Citation Index, DARE and
      LILACS were searched through 30 July 2010. SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials comparing the effects of RP versus WW for
      clinically localised prostate cancer. DATA COLLECTION AND ANALYSIS: Data
      extraction and quality assessment were carried out independently by two authors.
      MAIN RESULTS: Two trials met the inclusion criteria. Both trials commenced prior
      to the widespread availability of prostate-specific antigen (PSA) screening;
      hence the results may not be applicable to men with PSA-detected disease.One
      trial (N = 142), conducted in the US, was judged to be of poor quality. All cause
      (overall) mortality was not significantly different between RP and WW groups
      after fifteen years of follow up (Hazard Ratio (HR) 0.9 (95% Confidence Interval
      (CI) 0.56 to 1.43).The second trial (N = 695), conducted in Scandinavia, was
      judged to be of good quality. After 12 years of follow up, the trial results were
      compatible with a beneficial effect of RP on the risks of overall mortality,
      prostate cancer mortality and distant metastases compared with WW but the precise
      magnitude of the effect is uncertain as indicated by the width of the confidence
      intervals for all estimates (risk difference (RD) -7.1% (95% CI -14.7 to 0.5); RD
      -5.4% (95% CI -11.1 to 0.2); RD -6.7% (95% CI -13.2 to -0.2), respectively).
      Compared to WW, RP increased the absolute risks of erectile dysfunction (RD 35%
      (95% CI 25 to 45)) and urinary leakage (RD 27% (95% CI 17 to 37)). These
      estimates must be interpreted cautiously as they are derived from data obtained
      from a self-administered questionnaire survey of a sample of the trial
      participants (N = 326), no baseline quality of life data were obtained and nerve
      sparing surgery was not routinely performed on trial participants undergoing RP.
      AUTHORS' CONCLUSIONS: The existing trials provide insufficient evidence to allow
      confident statements to be made about the relative beneficial and harmful effects
      of RP and WW for patients with localised prostate cancer. The results of ongoing
      trials should help to inform treatment decisions for men with screen-detected
      localised prostate cancer.

PMID- 21069691
TI  - Human albumin for intradialytic hypotension in haemodialysis patients.
AB  - BACKGROUND: Intradialytic hypotension (IDH) occurs in 20% to 55% of haemodialysis
      sessions and is more frequent among patients on long-term haemodialysis.
      Symptomatic IDH is generally defined as a decrease in systolic blood pressure
      (BP) of at least 10 mm Hg or a systolic BP less than 100 mm Hg, with symptoms
      such as cramps, nausea, vomiting, and dizziness. IDH is managed acutely by volume
      expansion through the intravenous administration of fluids. OBJECTIVES: To
      compare the benefits and harms of volume expansion with human albumin, alone or
      in combination with crystalloid or non-protein colloids, for treating IDH in
      haemodialysis patients. SEARCH STRATEGY: The Cochrane Renal Group's Specialised
      Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2010, Issue 9) MEDLINE (1966 to Oct 2009), and EMBASE (1980 to
      Oct 2009) were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs),
      quasi-RCTs as well as randomised crossover studies were to be included. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      trial quality. Relative risk (RR) was to be used to analyse dichotomous variables
      and mean difference (MD) used to analyse continuous variables. MAIN RESULTS: One
      double blind randomised crossover trial met the inclusion criteria and compared
      5% albumin to normal saline in patients with a previous history of IDH. Results
      from 45 assessable participants did not lead to rejection of the null hypothesis
      of no difference between 5% albumin and normal saline in the primary outcome
      measure of percentage target ultrafiltration achieved, nor in 11/12 secondary
      outcomes. Additional (unblinded) saline was given less often when 5% albumin was
      used compared with saline (16% versus 36%, P = 0.04). However, the volume of
      additional fluid administered was similar in both groups. There were no
      significant differences in the nursing time required to treat IDH and the time to
      restore BP. AUTHORS' CONCLUSIONS: No randomised or controlled trial was
      identified comparing albumin to crystalloids (other than normal saline) or non
      protein colloids, or a combination of both, in the treatment of symptomatic
      hypotension during dialysis. One double blind crossover RCT in 45 assessable
      patients showed that 5% albumin is not superior to normal saline for the
      treatment of symptomatic hypotension in maintenance haemodialysis patients with a
      previous history of IDH. Given the cost and relative rarity of albumin use
      compared to saline, saline should be first line of therapy for treatment of IDH
      in stable dialysis patients.

PMID- 21069690
TI  - Clozapine versus other atypical antipsychotics for schizophrenia.
AB  - BACKGROUND: Clozapine is an atypical antipsychotic demonstrated to be superior in
      the treatment of refractory schizophrenia which causes fewer movement disorders.
      Clozapine, however, entails a significant risk of serious blood disorders such as
      agranulocytosis which could be potentially fatal. Currently there are a number of
      newer antipsychotics which have been developed with the purpose to find both a
      better tolerability profile and a superior effectiveness. OBJECTIVES: To compare
      the clinical effects of clozapine with other atypical antipsychotics (such as
      amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole,
      ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia
      like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Groups
      Register (June 2007) and reference lists of all included randomised controlled
      trials. We also manually searched appropriate journals and conference proceedings
      relating to clozapine combination strategies and contacted relevant
      pharmaceutical companies. SELECTION CRITERIA: All relevant randomised, at least
      single-blind trials, comparing clozapine with other atypical antipsychotics, any
      dose and oral formulations, for people with schizophrenia or related disorders.
      DATA COLLECTION AND ANALYSIS: We selected trials and extracted data
      independently. For dichotomous data we calculated relative risks (RR) and their
      95% confidence intervals (CI) based on a random-effects model. We calculated
      numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we
      calculated mean differences (MD) again based on a random-effects model. MAIN
      RESULTS: The review currently includes 27 blinded randomised controlled trials,
      which involved 3099 participants. Twelve randomised control trials compared
      clozapine with olanzapine, five with quetiapine, nine with risperidone, one with
      ziprasidone and two with zotepine. Attrition from these studies was high (overall
      30.1%), leaving the interpretation of results problematic. Clozapine had a higher
      attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI
      1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11
      to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the
      trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23
      to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of
      clozapine.Clozapine was more efficacious than zotepine in improving the
      participants general mental state (BPRS total score: 1 RCT, n=59, MD -6.00 CI 
      9.83 to -2.17), but not consistently more than olanzapine, quetiapine,
      risperidone and ziprasidone. There was no significant difference between
      clozapine and olanzapine or risperidone in terms of positive or negative symptoms
      of schizophrenia. According to two studies from China quetiapine was more
      efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99
      to 3.48).Clozapine produced somewhat fewer extrapyramidal side-effects than
      risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to
      0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2
      to 5). More participants in the clozapine group showed decreased white blood
      cells than those taking olanzapine, more hypersalivation and sedation than those
      on olanzapine, risperidone and quetiapine and more seizures than people on
      olanzapine and risperidone. Also clozapine produced an important weight gain not
      seen with risperidone.Other differences in adverse effects were less documented
      and should be replicated, for example, clozapine did not alter prolactin levels
      whereas olanzapine, risperidone and zotepine did; compared with quetiapine,
      clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and
      compared with quetiapine and risperidone clozapine produced a higher increase of
      triglyceride levels. Other findings that should be replicated were: clozapine
      improved social functioning less than risperidone and fewer participants in the
      clozapine group had to be hospitalised to avoid suicide attempts compared to
      olanzapine.Other important outcomes such as service use, cognitive functioning,
      satisfaction with care or quality of life were rarely reported. AUTHORS'
      CONCLUSIONS: Clozapine may be a little more efficacious than zotepine and
      risperidone but further trials are required to confirm this finding. Clozapine
      differs more clearly in adverse effects from other second generation
      antipsychotics and the side-effect profile could be key in the selection of
      treatment depending on the clinical situation and a patient's preferences. Data
      on other important outcomes such as cognitive functioning, quality of life, death
      or service use are currently largely missing, making further large and well
      designed trials necessary. It is also important to take into account that the
      large number of people leaving the studies early limits the validity and
      interpretation of our findings.

PMID- 21069692
TI  - Pharmacological treatments for fatigue associated with palliative care.
AB  - BACKGROUND: In healthy individuals, fatigue is a protective response to physical
      or mental stress, often relieved by rest. By contrast, in palliative care
      patients fatigue can be severely debilitating, thereby impacting daily activity
      and quality of life, often with rest not counteracting fatigue. Fatigue
      frequently occurs in patients with advanced disease and modalities treating
      cancer often contribute or cause fatigue. Further complicating issues are its
      multidimensionality, subjective nature, and lack of a consensus definition of
      fatigue. Pathophysiology is not fully understood and evidence-based treatment
      approaches are needed. OBJECTIVES: The objective was to determine efficacy of
      pharmacological treatments on non-specific fatigue in palliative care. The focus
      was on patients at an advanced stage of disease, including cancer and other
      chronic diseases associated with fatigue, aiming to relieve fatigue. Studies
      aiming at curative treatment (e.g. surgical intervention for early breast cancer)
      were not included. SEARCH STRATEGY: We searched EMBASE; Psych Lit, CENTRAL and
      MEDLINE to June 2009. SELECTION CRITERIA: We considered randomised controlled
      trials (RCTs) concerning adult palliative care with focus on pharmacological
      treatment of fatigue. The primary outcome had to be non-specific fatigue (or
      related terms such as asthenia). DATA COLLECTION AND ANALYSIS: Results were
      screened and included if they met the selection criteria. If two or more studies
      were identified that investigated a specific drug in a population with the same
      disease, meta-analysis was conducted. In addition, comparison of type of drug
      investigated in a specific population as well as comparison of frequent adverse
      effects of fatigue treatment was done by creating overview tables. MAIN RESULTS:
      More than 2000 publications were screened, and 22 met inclusion criteria. In
      total, data from 11 drugs and 1632 participants were analysed. Studies
      investigating amantadine, pemoline, and modafinil in participants with Multiple
      Sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from
      advanced cancer and fatigue could be used for meta-analysis. Amantadine in MS and
      methylphenidate in cancer patients showed a superior effect. Most studies had low
      participant numbers and were heterogenous. AUTHORS' CONCLUSIONS: Based on limited
      evidence, we cannot recommend a specific drug for treatment of fatigue in
      palliative care patients. Surprisingly, corticosteroids have not been a research
      focus for fatigue treatment, although these drugs are frequently used. Recent
      fatigue research seems to focus on modafinil, which may be beneficial although
      there is no evidence currently. Amantadine and methylphenidate should be further
      examined. Consensus regarding fatigue assessment in advanced disease is needed.

PMID- 21069693
TI  - Probiotics for treating persistent diarrhoea in children.
AB  - BACKGROUND: Persistent diarrhoea (diarrhoea lasting more than 14 days) accounts
      for one third of all diarrhoea related deaths in developing countries in some
      studies. Probiotics may help treatment. OBJECTIVES: To evaluate probiotics for
      treating persistent diarrhoea in children. SEARCH STRATEGY: In August 2010, we
      searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL,
      MEDLINE, EMBASE, and LILACS. We also contacted authors of included trials and
      organizations working in the field, and checked reference lists. SELECTION
      CRITERIA: Randomized controlled trials comparing a specified probiotic agent with
      placebo or no probiotic in children with persistent diarrhoea. DATA COLLECTION
      AND ANALYSIS: Two review authors assessed the eligibility, risk of bias,
      extracted and analysed data. Differences were resolved by discussion. Statistical
      analysis were performed using the fixed-effect model and the results were
      expressed as mean difference (MD) for continuous outcomes with 95% confidence
      intervals (CI). MAIN RESULTS: Four trials were included, with a total number of
      464 participants; one trial had a low risk of bias. Meta-analysis showed that
      probiotics reduced the duration of persistent diarrhoea (mean difference 4.02
      days, 95% CI 4.61 to 3.43 days, n=324, 2 trials). Stool frequency was reduced
      with probiotics in two trials. One trial reported a shorter hospital stay, which
      was significant, but numbers were small. No adverse events were reported.
      AUTHORS' CONCLUSIONS: There is limited evidence suggesting probiotics may be
      effective in treating persistent diarrhoea in children.

PMID- 21069694
TI  - Deferasirox for managing iron overload in people with myelodysplastic syndrome.
AB  - BACKGROUND: The myelodysplastic syndrome (MDS) comprises a diverse group of
      haematopoietic stem cell disorders. Due to symptomatic anaemia most patients
      require supportive therapy including repeated red blood cell (RBC) transfusions.
      In combination with increased iron absorption, this contributes to the
      accumulation of iron resulting in secondary iron overload and the risk of organ
      dysfunction and reduced life expectancy. Since the human body has no natural
      means of getting rid of excess iron, iron chelation therapy is usually
      recommended. However, whether the new oral chelator deferasirox leads to relevant
      benefit is unclear. OBJECTIVES: To assess the effectiveness and safety of oral
      deferasirox in people with myelodysplastic syndrome and iron overload. SEARCH
      STRATEGY: We searched MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web
      of Science, Derwent Drug File, XTOXLINE and three trial registries: Current
      Controlled Trials: www.controlled-trials.com, ClinicalTrials.gov:
      www.clinicaltrials.gov, ICTRP: www.who.int./ictrp/en/. Most recent searches of
      these databases: June 2010. SELECTION CRITERIA: Randomised controlled trials
      comparing deferasirox with no therapy/placebo or with another iron chelating
      treatment schedule. DATA COLLECTION AND ANALYSIS: No studies eligible for
      inclusion in this review were identified. MAIN RESULTS: No studies were included
      in this review. However, we identified one ongoing study comparing deferasirox
      with deferoxamine. AUTHORS' CONCLUSIONS: We planned to report evidence from
      randomised clinical trials evaluating the effectiveness of deferasirox compared
      to either placebo/no treatment or other chelating regimens such as deferoxamine
      in people with myelodysplastic syndrome. However, no completed randomised trials
      addressing this question could be identified.One ongoing randomised study
      comparing deferasirox with placebo was identified and preliminary data will
      hopefully be available soon. These results will be important to inform physicians
      and patients on the advantages and disadvantages of this treatment option.

PMID- 21069695
TI  - Pain relief for outpatient hysteroscopy.
AB  - BACKGROUND: Hysteroscopy is increasingly performed in an outpatient setting. The
      primary reason for failure is pain. There is no consensus upon the routine use of
      analgesia during hysteroscopy. OBJECTIVES: The aim of the study was to compare
      the effectiveness of different types of pharmacological interventions for pain
      relief in patients undergoing hysteroscopy. SEARCH STRATEGY: A search of medical
      literature databases including PubMed, EMBASE, PsycINFO and CINHAL (to February
      2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating
      pharmacological interventions for pain relief during hysteroscopy were
      investigated. DATA COLLECTION AND ANALYSIS: Results for each study were expressed
      as a standardised mean difference with 95% confidence interval and combined for
      meta-analysis with Revman 5 software. MAIN RESULTS: Twenty-four RCTS were
      identified involving a total of 3155 participants, with 15 studies included in
      the meta-analysis.Meta-analysis (nine RCTs, 1296 participants) revealed a
      significant reduction in the mean pain score for the use of local anaesthetics
      during the procedure compared with placebo (SMD -0.45, 95% CI -0.73 to -0.17,
      I(2) = 82%).Meta-analysis (4 RCTs, 454 participants) demonstrated a significant
      reduction in the mean pain score for the use of local anaesthetics within 30
      minutes after the procedure compared with placebo (SMD -0.51, 95% CI -0.81 to 
      0.21, I(2) = 54%).There was no significant reduction in the mean pain score with
      the use of NSAIDS or opioid analgesics compared with placebo during or within 30
      minutes after the procedure.There was no significant reduction in the mean pain
      score with the use of local anaesthetics, NSAIDS or opioid analgesics compared
      with placebo more than 30 minutes after the procedure.There was no significant
      difference between the number of incidents of failure to complete the procedure
      due to cervical stenosis between the intervention and control groups (OR 1.31,
      95% CI 0.66 to 2.59; 6 RCTs, 805 participants).There were significantly fewer
      incidents of failure to complete the procedure due to pain in the intervention
      group than in the control group (OR 0.29, 95% CI 0.12 to 0.69; two studies, 330
      participants).Meta-analysis demonstrated no significant difference between the
      intervention and placebo groups with regards to adverse effects. AUTHORS'
      CONCLUSIONS: There was a significant reduction in the mean pain score with the
      use of analgesia during and within 30 minutes after outpatient hysteroscopy. 

PMID- 21069696
TI  - Different communication strategies for disclosing results of diagnostic prenatal
      testing.
AB  - BACKGROUND: Any screening program aiming to reassure pregnant women that their
      unborn baby is healthy will cause anxiety while waiting for the test results.
      OBJECTIVES: 1) To determine if revealing amniocentesis or chorionic villous
      sampling (CVS) results on a fixed date alters maternal anxiety during the waiting
      period, compared with a policy of revealing the result "when available" (i.e.
      variable date). 2) To evaluate whether issuing early results from a rapid
      molecular test alters maternal anxiety during the waiting period. 3) To evaluate
      whether different methods of communication (telephone, fax, email, face to face)
      have any impact on the parents' satisfaction and anxiety levels. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31
      August 2010). SELECTION CRITERIA: All published and unpublished randomised
      trials, in which methods of issuing prenatal test results are compared. DATA
      COLLECTION AND ANALYSIS: Two review authors (Faris Mujezinovic and Zarko
      Alfirevic) assessed eligibility and trial quality and performed data extraction.
      MAIN RESULTS: Two studies (involving 286 women) from amniocentesis (but none from
      CVS) compared the impact of communicating results of rapid testing with waiting
      for definitive karyotype. Unfortunately, it was not possible to perform pooled
      analysis because one study reported only median (interquartile range) data,
      presumably because the data were not normally distributed.One study reported a
      statistically significant reduction in the average anxiety during the waiting
      period for women who had had a rapid test compared with those who had not (mean
      difference (MD) -2.30, 95% confidence intervals (CI) -3.08 to - 1.52). The other
      study compared median (interquartile range) for the trait- and state-anxiety
      scores and found no difference between the two groups. AUTHORS' CONCLUSIONS: We
      found no conclusive evidence that, while waiting for the full karyotype following
      amniocentesis, issuing results from a rapid analysis reduces maternal anxiety.
      The limited evidence from the two trials included in this review does not help
      resolve the dilemma about whether full karyotyping should be abandoned in favour
      of limited rapid testing for women undergoing Down's syndrome screening. This
      choice will rest on clinical arguments and cost-effectiveness rather than impact
      on anxiety.There is also no evidence to support the view that issuing
      amniocentesis results as soon as they are available is more user friendly than
      using a pre-defined fixed date. Studies evaluating the effect of different
      strategies for disclosing results on women anxiety for CVS are needed.

PMID- 21069697
TI  - Community-based intervention packages for reducing maternal and neonatal
      morbidity and mortality and improving neonatal outcomes.
AB  - BACKGROUND: While maternal, infant and under-five child mortality rates in
      developing countries have declined significantly in the past two to three
      decades, newborn mortality rates have reduced much more slowly. While it is
      recognised that almost half of the newborn deaths can be prevented by scaling up
      evidence-based available interventions such as tetanus toxoid immunisation to
      mothers; clean and skilled care at delivery; newborn resuscitation; exclusive
      breastfeeding; clean umbilical cord care; management of infections in newborns,
      many require facility based and outreach services. It has also been stated that a
      significant proportion of these mortalities and morbidities could also be
      potentially addressed by developing community-based packages interventions which
      should also be supplemented by developing and strengthening linkages with the
      local health systems. Some of the recent community-based studies of interventions
      targeting women of reproductive age have shown variable impacts on maternal
      outcomes and hence it is uncertain if these strategies have consistent benefit
      across the continuum of maternal and newborn care. OBJECTIVES: To assess the
      effectiveness of community-based intervention packages in reducing maternal and
      neonatal morbidity and mortality; and improving neonatal outcomes. SEARCH
      STRATEGY: We searched The Cochrane Pregnancy and Childbirth Group's Trials
      Register (January 2010), World Bank's JOLIS (12 January 2010), BLDS at IDS and
      IDEAS database of unpublished working papers (12 January 2010), Google and Google
      Scholar (12 January 2010). SELECTION CRITERIA: All prospective randomised and
      quasi-experimental trials evaluating the effectiveness of community-based
      intervention packages in reducing maternal and neonatal mortality and
      morbidities; and improving neonatal outcomes. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed trial quality and extracted the data. MAIN
      RESULTS: The review included 18 cluster-randomised/quasi-randomised trials,
      covering a wide range of interventional packages, including two subsets from one
      trial. We incorporated data from these trials using generic inverse variance
      method in which logarithms of risk ratio estimates were used along with the
      standard error of the logarithms of risk ratio estimates. Our review did not show
      any reduction in maternal mortality (risk ratio (RR) 0.77; 95% confidence
      interval (CI) 0.59 to 1.02, random-effects (10 studies, n = 144,956), I2 39%, P
      value 0.10. However, significant reduction was observed in maternal morbidity (RR
      0.75; 95% CI 0.61 to 0.92, random-effects (four studies, n = 138,290), I2 28%;
      neonatal mortality (RR 0.76; 95% CI 0.68 to 0.84, random-effects (12 studies, n =
      136,425), I2 69%, P value < 0.001), stillbirths (RR 0.84; 95% CI 0.74 to 0.97,
      random-effects (11studies, n = 113,821), I2 66%, P value 0.001) and perinatal
      mortality (RR 0.80; 95% CI 0.71 to 0.91, random-effects (10 studies, n =
      110,291), I2 82%, P value < 0.001) as a consequence of implementation of
      community-based interventional care packages. It also increased the referrals to
      health facility for pregnancy related complication by 40% (RR 1.40; 95% CI 1.19
      to 1.65, fixed-effect (two studies, n = 22,800), I2 0%, P value 0.76), and
      improved the rates of early breastfeeding by 94% (RR 1.94; 95% CI 1.56 to 2.42,
      random-effects (six studies, n = 20,627), I2 97%, P value < 0.001). We assessed
      our primary outcomes for publication bias, but observed no such asymmetry on the
      funnel plot. AUTHORS' CONCLUSIONS: Our review offers encouraging evidence of the
      value of integrating maternal and newborn care in community settings through a
      range of interventions which can be packaged effectively for delivery through a
      range of community health workers and health promotion groups. While the
      importance of skilled delivery and facility-based services for maternal and
      newborn care cannot be denied, there is sufficient evidence to scale up community
      based care through packages which can be delivered by a range of community-based
      workers.

PMID- 21069698
TI  - Milrinone for persistent pulmonary hypertension of the newborn.
AB  - BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a clinical
      syndrome characterized by suboptimal oxygenation as a result of sustained
      elevation in pulmonary vascular resistance after birth. Currently, the
      therapeutic mainstay for PPHN is optimal lung inflation and selective
      vasodilatation with inhaled nitric oxide (iNO). However, iNO is not available in
      all countries and not all infants will respond to iNO. Milrinone is a
      phosphodiesterase III inhibitor which induces pulmonary vasodilatation by its
      actions through a cyclic adenylate monophosphate mediated signaling pathway.
      OBJECTIVES: To assess efficacy and safety in infants with PPHN either treated
      with: milrinone compared with placebo or no treatment; milrinone compared with
      iNO; milrinone as an adjunct to iNO compared with iNO alone; milrinone compared
      with potential treatments for PPHN other than iNO. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue
      2, 2010), MEDLINE and EMBASE databases from their inception until January 2010.
      We searched the reference lists of potentially relevant studies without any
      language restriction. SELECTION CRITERIA: Fully published randomized controlled
      trials (RCTs) and quasi-RCTs comparing milrinone with placebo, iNO or potential
      treatments other than iNO in neonates with PPHN were included if trials reported
      any clinical outcome. DATA COLLECTION AND ANALYSIS: We found no studies meeting
      the criteria for inclusion in this review. MAIN RESULTS: We found no studies
      meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: The
      efficacy and safety of milrinone in the treatment of PPHN are not known and its
      use should be restricted within the context of RCTs. Such studies should address
      a comparison of milrinone with placebo (in clinical situations where iNO is not
      available) or, in well resourced countries, should compare milrinone with iNO or
      as an adjunct to iNO compared with iNO alone.

PMID- 21069699
TI  - Active cycle of breathing technique for cystic fibrosis.
AB  - BACKGROUND: People with cystic fibrosis (CF) experience chronic airway infections
      as a result of mucus build up within the lungs. Repeated infections often cause
      lung damage and disease. Airway clearance therapies aim to improve mucus
      clearance, increase sputum production, and improve airway function. The active
      cycle of breathing technique (ACBT) is an airway clearance method that uses a
      cycle of techniques to loosen airway secretions including breathing control,
      thoracic expansion exercises, and the forced expiration technique. OBJECTIVES: To
      compare the clinical effectiveness of ACBT with other airway clearance therapies
      in CF. SEARCH STRATEGY: We searched the Cochrane CF Trials Register, compiled
      from electronic database searches and handsearching of journals and conference
      abstract books. We also searched the reference lists of relevant articles and
      reviews.Last search: 05 August 2010. SELECTION CRITERIA: Randomised or quasi
      randomised controlled clinical studies, including crossover studies, comparing
      ACBT with other airway clearance therapies in CF. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened each article, abstracted data and
      assessed the risk of bias of each study. MAIN RESULTS: Fifty-eight studies were
      identified of which 17 (346 participants) met the inclusion criteria. Four
      randomised controlled studies (98 participants) were included in the meta
      analysis; three were of crossover design. The 13 remaining studies were crossover
      studies with inadequate reports for complete assessment.Included studies compared
      ACBT to autogenic drainage, airway oscillating devices, high frequency chest
      compression devices, and conventional chest physiotherapy. Patient preference
      varied: more patients preferred autogenic drainage over ACBT, more preferred ACBT
      over airway oscillating devices, and more were comfortable with ACBT versus high
      frequency chest compression. No significant difference was seen in sputum weight
      between ACBT and autogenic drainage or between ACBT and airway oscillating
      devices. There was no significant difference in lung function and the number of
      pulmonary exacerbations between ACBT and ACBT plus conventional chest
      physiotherapy. All other outcomes were either not measured or had insufficient
      data for analysis. AUTHORS' CONCLUSIONS: There is insufficient evidence to
      support or reject the use of ACBT over any other airway clearance therapy. Four
      studies, with four different comparators, found that ACBT was comparable to other
      therapies in outcomes such as patient preference, lung function, sputum weight,
      oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are
      needed to more adequately assess the effects of ACBT on outcomes important for
      patients such as quality of life and patient preference.

PMID- 21069700
TI  - Paracetamol (acetaminophen) with or without an antiemetic for acute migraine
      headaches in adults.
AB  - BACKGROUND: Migraine is a common, disabling condition and a burden for the
      individual, health services and society. Many sufferers choose not to, or are
      unable to, seek professional help and rely on over-the-counter analgesics. Co
      therapy with an antiemetic should help to reduce nausea and vomiting commonly
      associated with migraine. OBJECTIVES: To determine the efficacy and tolerability
      of paracetamol (acetaminophen), alone or in combination with an antiemetic,
      compared to placebo and other active interventions in the treatment of acute
      migraine in adults. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE,
      EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010.
      SELECTION CRITERIA: We included randomised, double-blind, placebo- or active
      controlled studies using self-administered paracetamol to treat a migraine
      headache episode, with at least 10 participants per treatment arm. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality
      and extracted data. Numbers of participants achieving each outcome were used to
      calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared
      to placebo or other active treatment. MAIN RESULTS: Ten studies (2769
      participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination
      with an antiemetic, with placebo or other active comparators, mainly sumatriptan
      100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs
      of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief,
      respectively, when medication was taken for moderate to severe pain. Nausea,
      photophobia and phonophobia were reduced more with paracetamol than with placebo
      at 2 hours (NNTs of 7 to 11); more individuals were free of any functional
      disability at 2 hours with paracetamol (NNT 10); and fewer participants needed
      rescue medication over 6 hours (NNT 6).Paracetamol 1000 mg plus metoclopramide 10
      mg was not significantly different from oral sumatriptan 100 mg for 2-hour
      headache relief; there were no 2-hour pain-free data. There was no significant
      difference between the paracetamol plus metoclopramide combination and
      sumatriptan for relief of "light/noise sensitivity" at 2 hours, but slightly more
      individuals needed rescue medication over 24 hours with the combination therapy
      (NNT 17).Adverse event rates were similar between paracetamol and placebo, and
      between paracetamol plus metoclopramide and sumatriptan. No serious adverse
      events occurred with paracetamol alone, but more "major" adverse events occurred
      with sumatriptan than with the combination therapy (NNH 32). AUTHORS'
      CONCLUSIONS: Paracetamol 1000 mg alone is an effective treatment for acute
      migraine headaches, and the addition of 10 mg metoclopramide gives short-term
      efficacy equivalent to oral sumatriptan 100 mg. Adverse events with paracetamol
      did not differ from placebo; "major" adverse events were slightly more common
      with sumatriptan than with paracetamol plus metoclopramide.

PMID- 21069701
TI  - Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in
      antagonist assisted reproductive technology cycles.
AB  - BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonist protocols for
      pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic
      sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte
      maturation. Currently, human chorionic gonadotropin (HCG) is still the standard
      medication for this purpose. The effectiveness of triggering with a GnRH agonist
      compared to HCG measured as pregnancy and ovarian hyperstimulation(OHSS) rates
      are unknown. OBJECTIVES: To compare the effectiveness of a GnRH agonist with HCG
      for triggering final oocyte maturation in IVF and ICSI patients undergoing
      controlled ovarian hyperstimulation in a GnRH antagonist protocol followed by
      embryo transfer.  SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE , EMBASE, the National Research Register,
      the Medical Research Council's Clinical Trials Register, and the NHS Centre for
      Reviews and Dissemination database. We also examined the reference lists of all
      known primary studies and review articles, citation lists of relevant
      publications and abstracts of major scientific meetings. SELECTION CRITERIA: All
      randomised controlled studies (RCTs) reporting data comparing clinical outcomes
      for women undergoing IVF and ICSI cycles and using a GnRH agonist in comparison
      with HCG for final oocyte maturation triggering. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed trial quality and extracted data. MAIN
      RESULTS: We identified 11 RCTs (n = 1055). Eight studies assessed fresh
      autologous cycles and three studies assessed donor-recipient cycles. In fresh
      autologous cycles, GnRH agonist was less effective than HCG in terms of the live
      birth rate per randomised woman (OR 0.44, 95% CI 0.29 to 0.68; 4 RCTs) and
      ongoing pregnancy rate per randomised woman (OR 0.45, 95% CI 0.31 to 0.65; 8
      RCTs). For a group with a 30% live birth or ongoing pregnancy rate using HCG, the
      rate would be between 12% and 22% using an GnRH agonist. Moderate to severe
      ovarian hyperstimulation syndrome (OHSS) incidence per randomised woman was
      significantly lower in the GnRH agonist group compared to the HCG group (OR 0.10,
      95% CI 0.01 to 0.82; 5 RCTs). For a group with a 3% OHSS rate using HCG the rate
      would be between 0% and 2.6% using GnRH agonist. In donor recipient cycles, there
      was no evidence of a statistical difference in the live birth rate per randomised
      woman (OR 0.92, 95% CI 0.53 to 1.61; 1 RCT). AUTHORS' CONCLUSIONS: We do not
      recommend that GnRH agonists be routinely used as a final oocyte maturation
      trigger in fresh autologous cycles because of lowered live birth rates and
      ongoing pregnancy rates. An exception could be made for women with high risk of
      OHSS, after appropriate counselling.

PMID- 21069702
TI  - Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for adults
      with swallowing disturbances.
AB  - BACKGROUND: A number of conditions compromise the passage of food along the
      digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven
      technique, although its prolonged use can lead to complications such as lesions
      to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration
      pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG),
      is generally used when there is a need for enteral nutrition for a longer time
      period. There is a high demand for PEG in patients with swallowing disorders,
      although there is no consistent evidence about its effectiveness and safety as
      compared to NGT. OBJECTIVES: To evaluate the effectiveness and safety of PEG as
      compared to NGT for adults with swallowing disturbances. SEARCH STRATEGY: We
      searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to
      August 2009, as well as contacting main authors in the subject area. There was no
      language restriction in the search. SELECTION CRITERIA: We planned to include
      randomised controlled trials comparing PEG versus NGT for adults with swallowing
      disturbances or dysphagia and indications for nutritional support, with any
      underlying diseases. The primary outcome was intervention failures (feeding
      interruption, blocking or leakage of the tube, no adherence to treatment). DATA
      COLLECTION AND ANALYSIS: Review authors performed selection, data extraction and
      evaluation of methodological quality of studies. For dichotomous and continuous
      variables, we used risk ratio (RR) and mean difference (MD), respectively with
      the random-effects statistical model and 95% confidence interval (CI). We assumed
      statistical heterogeneity when I(2) > 50%. MAIN RESULTS: We included nine
      randomised controlled studies. Intervention failure occurred in 19/156 patients
      in the PEG group and 63/158 patients in the NGT group (RR 0.24 (95%CI 0.08 to
      0.76, P = 0.01)) in favour of PEG. There was no statistically significant
      difference between comparison groups in complications (RR 1.00, 95%CI 0.91 to
      1.11, P = 0.93). AUTHORS' CONCLUSIONS: PEG was associated to a lower probability
      of intervention failure, suggesting the endoscopic procedure is more effective
      and safe as compared to NGT. There is no significant difference of mortality
      rates between comparison groups, and pneumonia irrespective of underlying disease
      (medical diagnosis). Future studies should include previously planned and
      executed follow-up periods, the gastrostomy technique, and the experience of the
      professionals to allow more detailed subgroup analysis.

PMID- 21069703
TI  - Percutaneous lines for delivering intravenous antibiotics in people with cystic
      fibrosis.
AB  - BACKGROUND: Percutaneous long lines (long intravenous lines) and short
      intravenous lines (also termed cannulae) are both used to deliver intravenous
      antibiotics in cystic fibrosis to treat respiratory exacerbations of the disease.
      The perceived advantage of a long intravenous line is a greater duration of line
      function, which has to be balanced against a technically more challenging
      insertion procedure, and the possibility of more discomfort on insertion.
      OBJECTIVES: To compare long intravenous lines with short intravenous lines in
      people with cystic fibrosis receiving intravenous antibiotics, in terms of
      lifespan of the line, ease of insertion, complication rates of the line and
      patient satisfaction. This will help patients and clinicians choose between
      devices. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Trials Register comprising references identified from
      comprehensive electronic database searches and handsearches of relevant journals
      and abstract books of conference proceedings.Date of most recent search: 26
      August 2010. SELECTION CRITERIA: Randomised studies comparing long intravenous
      lines lines with short intravenous lines or comparing different types of long
      intravenous lines. DATA COLLECTION AND ANALYSIS: We identified two studies, one
      comparing long intravenous lines with short intravenous lines, and one comparing
      two different types of long intravenous lines. MAIN RESULTS: Two studies (67
      participants) were included in the review. Based on the published reports, both
      studies had potential for bias in several domains. There is some evidence that
      long intravenous lines are superior to short intravenous lines. One study of 20
      participants found that the lifespan of a long intravenous line is longer than
      that of a short intravenous line, and that participants preferred the long
      intravenous lines to short intravenous lines. A further study of 47 participants
      found no difference in lifespan, or participant preference when comparing two
      different long intravenous lines (the Hydrocath and Vygon EC). Neither study was
      powered to detect differences in serious complications of the devices. AUTHORS'
      CONCLUSIONS: There is some evidence to support the use of long intravenous lines
      rather than short intravenous lines, in terms of lifespan of the line and patient
      satisfaction. There is no evidence to suggest that any one type of long
      intravenous line is superior, and currently choice of line should be determined
      by operator and patient preference. There are numerous devices available which
      are used in cystic fibrosis. Further research is required to identify clinically
      important differences between these devices.

PMID- 21069704
TI  - Booster dose vaccination for preventing hepatitis B.
AB  - BACKGROUND: Antibodies against hepatitis B surface antigen (HBs) wane over time
      after vaccination for hepatitis B (HB); hence, the duration of protection
      provided by the vaccine is still unknown but may be evaluated indirectly by
      measuring the anamnestic immune response to booster doses of vaccine. OBJECTIVES:
      To assess the benefits and harms of booster dose hepatitis B vaccination for
      preventing HB infection. SEARCH STRATEGY: We searched The Cochrane Hepato-biliary
      Group Controlled Trials Register, the Cochrane Central Register of Controlled
      Trials (CENTRAL) (Issue 4, 2010) in The Cochrane Library, MEDLINE, EMBASE,
      Science Citation Index Expanded, conference databases, and reference lists of
      articles to May 2010. We also contacted authors of articles and manufacturers.
      SELECTION CRITERIA: Randomised clinical trials addressing anamnestic immune
      response to booster of HB vaccine five years or more after primary vaccination in
      apparently healthy participants, vaccinated in a 3-dose or 4-dose schedules of HB
      vaccine without receiving additional dose or immunoglobulin. DATA COLLECTION AND
      ANALYSIS: Two authors made the decisions if the identified publications on
      studies met the inclusion criteria or not. Primary outcome measures included the
      proportion with anamnestic immune response in non-protected participants and
      signs of hepatitis B virus infection. Secondary outcomes were the proportion with
      local and systemic adverse event events developed following booster dose
      injection. Weighted proportion were planned to be reported with 95% confidence
      intervals. MAIN RESULTS: There were no eligible randomised clinical trials
      fulfilling the inclusion criteria of this review. AUTHORS' CONCLUSIONS: We were
      unable to identify randomised clinical trials on the topic. We need randomised
      clinical trials to formulate future booster policies for preventing hepatitis B
      infection.

PMID- 21069705
TI  - Recombinant human thyrotropin (rhTSH) aided radioiodine treatment for residual or
      metastatic differentiated thyroid cancer.
AB  - BACKGROUND: For patients with differentiated thyroid cancer (DTC) following
      thyroidectomy, thyroid hormone withdrawal (THW) for four to six weeks has been
      used for decades to increase serum thyroid-stimulating hormone (TSH)
      concentrations in order to enhance iodine-131 uptake by normal thyroid cells and
      differentiated thyroid tumour cells. Exogenous stimulation with recombinant human
      thyroid-stimulating hormone (rhTSH) offers an alternative to THW while avoiding
      the morbidity of hypothyroidism. However, the efficacy of rhTSH-aided iodine-131
      treatment for residual or metastatic DTC has not been prospectively assessed.
      OBJECTIVES: To assess the effects of rhTSH-aided radioiodine treatment for normal
      residual or metastatic DTC. SEARCH STRATEGY: We obtained studies from
      computerised searches of MEDLINE, EMBASE and The Cochrane Library (all until
      November 2009), and paper collections of conferences held in Chinese. SELECTION
      CRITERIA: Randomised controlled clinical trials and quasi-randomised controlled
      clinical trials comparing the effects of rhTSH with THW on iodine-131 treatment
      for residual or metastatic differentiated thyroid cancer with at least six months
      of follow up. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      risk of bias and extracted data. MAIN RESULTS: Altogether 223 patients with DTC
      participated in four trials. Overall, studies had a high risk of bias. We found
      no statistically significant differences between rhTSH and THW treatment in terms
      of successful ablation rate but significant benefits in radiation exposure to
      blood and bone marrow. One trial reported on benefits in some domains of health
      related quality of life. There were no deaths and no serious adverse effects in
      DTC patients treated with either rhTSH or THW. Maximum follow up was 12 months.
      None of the included trials investigated complete or partial remission of
      metastatic tumour, secondary malignancies or economic outcomes. We did not find
      sufficient data comparing rhTSH with THW-aided radioiodine treatment for
      metastatic DTC. AUTHORS' CONCLUSIONS: Results from four randomised controlled
      clinical trials suggest that rhTSH is as effective as THW on iodine-131 thyroid
      remnant ablation, with limited data on significant benefits in decreased whole
      body radiation exposure and health-related quality of life. It is still uncertain
      whether lower iodine-131 doses (1110 MBq or 1850 MBq versus 3700 MBq) are equally
      effective for remnant ablation under rhTSH stimulation. Randomised controlled
      clinical trials are needed to guide treatment selection for metastatic
      differentiated thyroid cancer.

PMID- 21069706
TI  - Interventions for women with endometrioma prior to assisted reproductive
      technology.
AB  - BACKGROUND: Endometriomata are cysts of endometriosis in the ovaries. As
      artificial reproductive technology (ART) cycles involve oocyte pickup from the
      ovaries, endometriomata may interfere with the outcome of ART. OBJECTIVES: To
      determine the effectiveness and safety of surgery, medical treatment, combination
      therapy or no treatment for improving reproductive outcomes among women with
      endometriomata, prior to undergoing ART cycles. SEARCH STRATEGY: The review
      authors searched: Cochrane Menstrual Disorders and Subfertility Group Specialised
      Register of trials, CENTRAL (The Cochrane Library), EMBASE, MEDLINE, PubMed,
      PsycINFO, CINAHL, DARE, trial registers for ongoing and registered trials,
      citation indexes, conference abstracts on the ISI Web of Knowledge, Clinical
      Study Results, OpenSIGLE (July 2010) and handsearched Fertility and Sterility
      (2008 to 2010). SELECTION CRITERIA: Randomised controlled trials of any medical,
      surgical or combination therapy or expectant management for endometriomata prior
      to ART. DATA COLLECTION AND ANALYSIS: The trials were independently identified
      and assessed for risk of bias by two authors. The authors of the trials that were
      potentially eligible for inclusion were contacted for additional information.
      Outcomes were expressed as Peto odds ratios and mean differences (MD). MAIN
      RESULTS: Eleven trials were identified of which seven were excluded and four with
      312 participants were included.No trial reported live birth outcomes. One trial
      compared gonadotropin-releasing hormone (GnRH) agonist with GnRH antagonist.
      There was no evidence of a difference for clinical pregnancy rate (CPR), however
      the number of mature oocytes retrieved (NMOR) was greater with GnRH agonists (MD 
      1.60, 95% CI -2.44 to -0.76) and the ovarian response was increased (estradiol
      (E2) levels on day of human chorionic gonadotropin (hCG) injection) (MD -456.30,
      95% CI -896.06 to -16.54).Surgery (aspiration or cystectomy) versus expectant
      management (EM) showed no evidence of a benefit for clinical pregnancy with
      either technique. Aspiration was associated with greater NMOR (MD 0.50, 95% CI
      0.02 to 0.98) and increased ovarian response (E2 levels on day of hCG injection)
      (MD 685.3, 95% CI 464.50 to 906.10) compared to EM.Cystectomy was associated with
      a decreased ovarian response to controlled ovarian hyperstimulation (COH) (MD 
      510.00, 95% CI -676.62 to -343.38); no evidence of an effect on the NMOR compared
      to EM. Aspiration versus cystectomy showed no evidence of a difference in CPR or
      the NMOR. AUTHORS' CONCLUSIONS: There was no evidence of an effect on
      reproductive outcomes in any of the four included trials. Further RCTs of
      management of endometrioma in women undergoing ART are required.

PMID- 21069707
TI  - Vitamin A supplementation during pregnancy for maternal and newborn outcomes.
AB  - BACKGROUND: The World Health Organization recommends routine vitamin A
      supplementation during pregnancy or lactation in areas with endemic vitamin A
      deficiency (where night blindness occurs), based on the expectation that
      supplementation will improve maternal and newborn outcomes including mortality,
      morbidity and prevention of anaemia or infection.   OBJECTIVES: To review the
      effects of supplementation of vitamin A, or one of its derivatives, during
      pregnancy, alone or in combination with other vitamins and micronutrients, on
      maternal and newborn clinical outcomes. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (15 July 2010). SELECTION
      CRITERIA: All randomised or quasi-randomised trials, including cluster-randomised
      trials, evaluating the effect of vitamin A supplementation in pregnant women.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all
      studies for inclusion and resolved any disagreement through discussion with a
      third person. We used pre-prepared data extraction sheets. MAIN RESULTS: We
      examined 88 reports of 31 trials, published between 1931 and 2010, for inclusion
      in this review. We included 16 trials, excluded 14, and one is awaiting
      assessment.Overall when trial results are pooled, Vitamin A supplementation does
      not affect the risk of maternal mortality (risk ratio (RR) 0.78, 95% confidence
      interval (CI) 0.55 to 1.10, 3 studies, Nepal, Ghana,UK ), perinatal mortality,
      neonatal mortality, stillbirth, neonatal anaemia, preterm birth or the risk of
      having a low birthweight baby. Vitamin A supplementation reduces the risk of
      maternal night blindness (risk ratio (RR) 0.70, 95% CI 0.60 to 0.82, 1 trial
      Nepal). In vitamin A deficient populations and HIV-positive women, vitamin A
      supplementation reduces maternal anaemia (risk ratio (RR) 0.64, 95% confidence
      interval (CI) 0.43 to 0.94, 3 trials, Indonesia, Nepal,Tanzania ). There is
      evidence that vitamin A supplements may reduce maternal clinical infection (RR
      0.37, 95% CI 0.18 to 0.77, 3 trials, South Africa, Nepal and UK).In HIV-positive
      women vitamin A supplementation given with other micronutrients was associated
      with fewer low birthweight babies (< 2.5 kg) in the supplemented group in one
      study (RR 0.67, CI 0.47 to 0.96). AUTHORS' CONCLUSIONS: The pooled results of two
      large trials in Nepal and Ghana (with almost 95,000 women) do not currently
      suggest a role for antenatal vitamin A supplementation to reduce maternal or
      perinatal mortality. However the populations studied were probably different with
      regard to baseline vitamin A status and there were problems with follow-up of
      women. There is good evidence that antenatal vitamin A supplementation reduces
      maternal anaemia for women who live in areas where vitamin A deficiency is common
      or who are HIV-positive. In addition the available evidence suggests a reduction
      in maternal infection, but these data are not of a high quality.

PMID- 21069715
TI  - Studies on the inference of protein binding regions across fold space based on
      structural similarities.
AB  - The emerging picture of a continuous protein fold space highlights the existence
      of non obvious structural similarities between proteins with apparent different
      topologies. The identification of structure resemblances across fold space and
      the analysis of similar recognition regions may be a valuable source of
      information towards protein structure-based functional characterization. In this
      work, we use non-sequential structural alignment methods (ns-SAs) to identify
      structural similarities between protein pairs independently of their SCOP
      hierarchy, and we calculate the significance of binding region conservation using
      the interacting residues overlap in the ns-SA. We cluster the binding inferences
      for each family to distinguish already known family binding regions from putative
      new ones. Our methodology exploits the enormous amount of data available in the
      PDB to identify binding region similarities within protein families and to
      propose putative binding regions. Our results indicate that there is a plethora
      of structurally common binding regions among proteins, independently of current
      fold classifications. We obtain a 6- to 8-fold enrichment of novel binding
      regions, and identify binding inferences for 728 protein families that so far
      lack binding information in the PDB. We explore binding mode analogies between
      ligands from commonly clustered binding regions to investigate the utility of our
      methodology. A comprehensive analysis of the obtained binding inferences may help
      in the functional characterization of protein recognition and assist rational
      engineering. The data obtained in this work is available in the download link at
      www.scowlp.org.

PMID- 21069723
TI  - Re-engineering specificity in 1,3-1, 4-beta-glucanase to accept branched
      xyloglucan substrates.
AB  - Family 16 carbohydrate active enzyme members Bacillus licheniformis 1,3-1,4-beta
      glucanase and Populus tremula x tremuloides xyloglucan endotransglycosylase
      (XET16-34) are highly structurally related but display different substrate
      specificities. Although the first binds linear gluco-oligosaccharides, the second
      binds branched xylogluco-oligosaccharides. Prior engineered nucleophile mutants
      of both enzymes are glycosynthases that catalyze the condensation between a
      glycosyl fluoride donor and a glycoside acceptor. With the aim of expanding the
      glycosynthase technology to produce designer oligosaccharides consisting of
      hybrids between branched xylogluco- and linear gluco-oligosaccharides, enzyme
      engineering on the negative subsites of 1,3-1,4-beta-glucanase to accept branched
      substrates has been undertaken. Removal of the 1,3-1,4-beta-glucanase major loop
      and replacement with that of XET16-34 to open the binding cleft resulted in a
      folded protein, which still maintained some beta-glucan hydrolase activity, but
      the corresponding nucleophile mutant did not display glycosynthase activity with
      either linear or branched glycosyl donors. Next, point mutations of the 1,3-1,4
      beta-glucanase beta-sheets forming the binding site cleft were mutated to
      resemble XET16-34 residues. The final chimeric protein acquired binding affinity
      for xyloglucan and did not bind beta-glucan. Therefore, binding specificity has
      been re-engineered, but affinity was low and the nucleophile mutant of the
      chimeric enzyme did not show glycosynthase activity to produce the target hybrid
      oligosaccharides. Structural analysis by X-ray crystallography explains these
      results in terms of changes in the protein structure and highlights further
      engineering approaches toward introducing the desired activity.

PMID- 21069716
TI  - Development of a new physics-based internal coordinate mechanics force field and
      its application to protein loop modeling.
AB  - We report the development of internal coordinate mechanics force field (ICMFF),
      new force field parameterized using a combination of experimental data for
      crystals of small molecules and quantum mechanics calculations. The main features
      of ICMFF include: (a) parameterization for the dielectric constant relevant to
      the condensed state (epsilon = 2) instead of vacuum, (b) an improved description
      of hydrogen-bond interactions using duplicate sets of van der Waals parameters
      for heavy atom-hydrogen interactions, and (c) improved backbone covalent geometry
      and energetics achieved using novel backbone torsional potentials and inclusion
      of the bond angles at the C(alpha) atoms into the internal variable set. The
      performance of ICMFF was evaluated through loop modeling simulations for 4-13
      residue loops. ICMFF was combined with a solvent-accessible surface area
      solvation model optimized using a large set of loop decoys. Conformational
      sampling was carried out using the biased probability Monte Carlo method.
      Average/median backbone root-mean-square deviations of the lowest energy
      conformations from the native structures were 0.25/0.21 A for four residues
      loops, 0.84/0.46 A for eight residue loops, and 1.16/0.73 A for 12 residue loops.
      To our knowledge, these results are significantly better than or comparable with
      those reported to date for any loop modeling method that does not take crystal
      packing into account. Moreover, the accuracy of our method is on par with the
      best previously reported results obtained considering the crystal environment. We
      attribute this success to the high accuracy of the new ICM force field achieved
      by meticulous parameterization, to the optimized solvent model, and the
      efficiency of the search method.

PMID- 21069729
TI  - Activating transcription factor 2 targets c-Fos, but not c-Jun, in growth plate
      chondrocytes.
AB  - Activating transcription factor 2 (ATF-2), c-Fos, and c-Jun belong to the bZIP
      family of transcription factors. Promoters of c-Fos, c-Jun, cyclin D1, and cyclin
      A are targets of ATF-2 in primary mouse chondrocytes. An ATF-2 expression vector
      was co-transfected with either c-Fos or c-Jun promoters in mutant ATF-2
      chondrocytes in order to show by luciferase assay that ATF-2 increased promoter
      activity of c-Fos, but not c-Jun. Chromatin immunoprecipitation (ChIP) assays
      revealed that ATF-2 bound with the c-Fos promoter at the -294 cyclic AMP response
      element (CRE) site, but did not bind to the TPA responsive element (TRE) or
      activating protein-1 (AP1) sites of the c-Jun promoter. Dominant-negative (dn) c
      Fos inhibited cyclin D1 promoter activity. However, dn c-Jun had minimal effect
      on this same promoter activity. c-Fos was capable of interactions with both the
      cyclin D1 CRE and AP1 sites, while c-Jun co-operated specifically with the cyclin
      D1 CRE site. Neither c-Fos nor c-Jun had any effect on cyclin A promoter
      activity. c-Fos was unable to bind to the cyclin A AP1 or CRE sites. In contrast
      c-Jun was competent in interactions with cyclin A AP1-2 as well as the CRE.

PMID- 21069730
TI  - EBV interferes with the sensitivity of Burkitt lymphoma Akata cells to etoposide.
AB  - Burkitt lymphoma (BL) commonly exhibits Epstein-Barr virus (EBV) positivity
      associated with latent chronic infection. Models of acute EBV infection have been
      associated with cellular resistance to apoptosis. However, the effect of latent
      long-term EBV infection on apoptosis induced by drugs is not well defined. To
      determine this, we have studied the response of the Akata EBV+ cell line (type I
      latency) to etoposide, before and after downregulating EBV gene expression. We
      observed that downregulating EBV nuclear antigen-1 (EBNA-1) expression with
      siRNAs reverted cellular sensitivity to etoposide. In accordance with this
      finding, Akata EBV+ cells showed increased sensitivity to etoposide, when
      compared to the Akata EBV- cells. We also observed that Akata EBV+ cells
      presented increased apoptosis levels and decreased Bcl-xL mRNA and protein
      levels, when compared to the Akata EBV- cells. In addition, Akata EBV+ cells
      contained less endoplasmic reticulum (ER) than EBV- cells. Finally,
      downregulation of EBV with EBNA-1 siRNAs caused an increase in the expression of
      Bcl-xL indicating that EBV is responsible for the differences found between the
      Akata EBV+ and EBV- cell lines.

PMID- 21069731
TI  - Hepatitis C virus E2 protein induce reactive oxygen species (ROS)-related
      fibrogenesis in the HSC-T6 hepatic stellate cell line.
AB  - Chronic infection of hepatitis C virus (HCV) leads to hepatic fibrosis and
      subsequently cirrhosis, although the underlying mechanisms have not been
      established. Previous studies have indicated that the binding of HCV E2 protein
      and CD81 on the surface of hepatic stellate cells (HSCs) lead to the increased
      protein level and activity of matrix metallopeptidase (MMP) 2, indicating that E2
      may involve in the HCV-induced fibrosis. This study was designed to investigate
      the involvement of HCV E2 protein in the hepatic fibrogenesis. Results showed
      that E2 protein may promote the expression levels of alpha-smooth muscle actin
      (alpha-SMA) and collagen alpha(I). Furthermore, several pro-fibrosis or pro
      inflammatory cytokines, including transforming growth factor (TGF)-beta1,
      connective tissue growth factor (CTGF), interleukin (IL)-6 and IL-1beta, were
      significantly increased in E2 transfected-HSC cell lines, while the expression of
      MMP-2 are also considerably increased. Moreover, the significant increases of
      CTGF and TGF-beta1 in a stable E2-expressing Huh7 cell line were also observed
      the same results. Further molecular studies indicated that the impact of E2
      protein on collagen production related to higher production of ROS and activated
      Janus kinase (JAK)1, JAK2 and also enhance the activation of ERK1/2 and p38,
      while catalase and inhibitors specific for JAK, ERK1/2, and p38 abolish E2
      enhanced expression of collagen alpha(I). Taken together, this study indicated
      that E2 protein involve in the pathogenesis of HCV-mediated fibrosis via an up
      regulation of collagen alpha(I) and oxidative stress, which is JAK pathway
      related.

PMID- 21069734
TI  - Crystal structure of isoamyl acetate-hydrolyzing esterase from Saccharomyces
      cerevisiae reveals a novel active site architecture and the basis of substrate
      specificity.

PMID- 21069732
TI  - PDGF-induced proliferation in human arterial and venous smooth muscle cells:
      molecular basis for differential effects of PDGF isoforms.
AB  - Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of
      arterial atherosclerosis and venous neointimal hyperplasia. We examined the
      effects of PDGF isoforms on smooth muscle cells (SMCs) from arterial and venous
      origins in order to further understand the differential responsiveness of these
      vasculatures to proliferative stimuli. Serum-starved human arterial and venous
      SMCs exhibited very different proliferative responses to PDGF isoforms. Whereas,
      proliferation of arterial SMCs was strongly stimulated by PDGF-AA, venous SMCs
      showed no proliferative response to PDGF-AA, but instead demonstrated a
      significantly greater proliferative response to PDGF-BB than arterial SMCs. Part
      of this difference could be attributed to differences in PDGF receptors
      expression. There was a 2.5-fold higher (P < 0.05) density of PDGF receptor-alpha
      (PDGF-Ralpha) and a 6.6-fold lower (P < 0.05) density of PDGF-Rbeta expressed on
      arterial compared to venous SMCs. Concomitant with an increased proliferative
      response to PDGF-AA in arterial SMCs was a marked PDGF-Ralpha activation,
      enhanced phosphorylation of ERK1/2 and Akt, a transient activation of c-Jun NH2
      terminal kinase (JNK), and a significant reduction in expression of the cell
      cycle inhibitor p27(kip1). This pattern of signaling pathway changes was not
      observed in venous SMCs. No phosphorylation of PDGF-Ralpha was detected after
      venous SMC exposure to PDGF-AA, but there was enhanced phosphorylation of ERK1/2
      and Akt in venous SMCs, similar to that seen in the arterial SMCs. PDGF-BB
      stimulation of venous SMC resulted in PDGF-Rbeta activation as well as
      transactivation of epidermal growth factor receptor (EGF-R); transactivation of
      EGF-R was not observed in arterial SMCs. These results may provide an explanation
      for the differential susceptibility to proliferative vascular diseases of
      arteries and veins.

PMID- 21069735
TI  - Transforming growth factor-beta induces epithelial to mesenchymal transition and
      suppresses the proliferation and transdifferentiation of cultured human
      pancreatic duct cells.
AB  - Pancreatic duct cells are considered a potential source of beta-cell
      regeneration, and transforming growth factor-beta (TGF-beta) has been suggested
      to perform an important role in these processes, but the underlying mechanism of
      the signal pathways, especially in humans, remains poorly understood. To evaluate
      the role of TGF-beta1, pancreatic duct cells were isolated from three brain-dead
      organ donors. Pancreatic cell clusters harvested after islet isolation were
      dispersed to single cells and cultured in monolayers, then treated with TGF
      beta1. We analyzed the characteristics of the cultured cells, the TGF-beta1
      intracellular signaling pathway, the proliferation, and transdifferentiation
      rates of the duct cells. We also evaluated the genes and protein expression
      patterns after TGF-beta1 treatment. After TGF-beta1 treatment, typical
      morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT
      phosphorylation, Ras downstream effectors, were increased. beta cell-specific
      transcription factors including PDX-1, Beta2/NeuroD, Ist-1, and NGN3 were
      markedly suppressed and the rate of transdifferentiation into beta cells was also
      suppressed. Genomic and proteomic analyses suggested that TGF-beta1 induces
      marked changes in a variety of structural genes and proteins associated with EMT.
      In conclusion, TGF-beta1 induces EMT in cultured human pancreatic duct cells, but
      suppresses its proliferation and transdifferentiation into beta cells. Our
      results are the first report of TGF-beta1 effects for EMT and ductal cell
      transdifferentiation and proliferation at the protein level in human pancreatic
      duct cells.

PMID- 21069736
TI  - Extracellular matrix modulates insulin production during differentiation of AR42J
      cells: functional role of Pax6 transcription factor.
AB  - Extracellular matrix (ECM) modulates differentiation of pancreatic beta-cells
      during development. However, the mechanism by which ECM proteins modulate
      differentiation is not totally clear. We investigated the effect of ECM proteins
      on differentiation beta-cells in vitro. We investigated the effect of basement
      membrane ECM on differentiation of AR42J cells and rat ductal cells. First, we
      examined the effect of reconstituted basement membrane, Matrigel on
      differentiation of AR42J cells induced by activin and betacellulin. Matrigel
      augmented insulin production and increased the expression of GLUT2, SUR1, and
      glucokinase. Among various transcription factors investigated, Matrigel markedly
      upregulated the expression of Pax6. When Pax6 was overexpressed in cells treated
      with activin and betacellulin, the expression of insulin was upregulated.
      Conversely, knockdown of Pax6 significantly reduced the insulin expression in
      cells cultured on Matrigel. The effects of Matrigel on insulin-production and
      induction of Pax6 were reproduced partially by laminin-1, a major component of
      Matrigel, and inhibited by anti-integrin-beta1 antibody. Matrigel also enhanced
      the activation of p38 mitogen-activated kinase induced by activin and
      betacellulin, which was inhibited by anti-beta1 antibody. Finally, the effect of
      Matrigel on differentiation was reproduced in rat cultured ductal cells, and
      Matrigel also increased the expression of Pax6. These results indicate that
      basement membrane ECM augments differentiation of pancreatic progenitor cells to
      insulin-secreting cells by upregulating the expression of Pax6. .

PMID- 21069737
TI  - Modification of proteins secreted by endothelial cells during modeled low gravity
      exposure.
AB  - The exposure of the human body to microgravity, conditions that occurs during
      space flights, causes significant changes in the cardiovascular system. Many cell
      types have been involved in these changes, and the endothelium seems to play a
      major role. In endothelial cells (EC), it has been shown that modeled low gravity
      impairs nitric oxide synthesis, cell adhesion, extracellular matrix composition,
      cytoskeleton organization, cytokines, and growth factors secretion. Nevertheless,
      detailed analysis of EC physiological changes induced by microgravity exposure is
      still lacking. Secretome analysis is one of the most promising approaches for the
      identification of biomarkers directly related to the physiopathological cellular
      state. In this study, we analyzed in details the modifications of EC secretome by
      using umbilical vein endothelial (HUVE) cells exposed to modeled low gravity
      conditions. By adopting a two-dimensional (2-D) proteomic approach, in
      conjunction with a technique for the compression of the dynamic range of
      proteins, we observed that modeled low gravity exposure of HUVE cells affected
      the secretion of proteins involved in the regulation of cytoskeleton assembly.
      Moreover, by using Luminex(r) suspension array systems, we found that the low
      gravity condition decreased in ECs the secretion of some key pro-inflammatory
      cytokines, including IL-1alpha and IL-8, and of the pro-angiogenic factor bFGF.
      On the contrary, microgravity increase the secretion of two chemokines (Rantes
      and Eotaxin), involved in leukocytes recruitment.

PMID- 21069738
TI  - Furanodienone inhibits cell proliferation and survival by suppressing ERalpha
      signaling in human breast cancer MCF-7 cells.
AB  - Estrogen receptor alpha (ERalpha) plays an important role in the development and
      progression of breast cancer and thus the attenuation of ERalpha activities is a
      promising treatment strategy. Furanodienone is one of the main bioactive chemical
      components of Rhizoma Curcumae which is commonly used in Chinese medicine for the
      treatment of cancer. In this study, we investigated the effects of furanodienone
      on human breast cancer MCF-7, T47D, and MDA-MB-231 cells. Our results showed that
      furanodienone could inhibit MCF-7, T47D, and MDA-MB-231 cells proliferation in a
      dose (10-160 uM) dependent manner. ERalpha-negative MDA-MB-231 cells were less
      sensitive to furanodienone than ERalpha-positive MCF-7 and T47D cells.
      Furanodienone could effectively block 17beta-estradiol (E2)-stimulated MCF-7 cell
      proliferation and cell cycle progression and induce apoptosis evidenced by the
      flow cytometric detection of sub-G1 DNA content and the appearance of apoptotic
      nuclei after DAPI staining. Furanodienone specifically down-regulated ERalpha
      protein and mRNA expression levels without altering ERbeta expression.
      Furanodienone treatment inhibited E2-stimulation of estrogen response element
      (ERE)-driven reporter plasmid activity and ablated E2-targeted gene (e.g., c-Myc,
      Bcl-2, and cyclin D1) expression which resulted in the inhibition of cell cycle
      progression and cell proliferation, and in the induction of apoptosis. Knockdown
      of ERalpha in MCF-7 cells by ERalpha-specific siRNA decreased the cell growth
      inhibitory effect of furanodienone. These findings suggest that effects of
      furanodienone on MCF-7 cells are mediated, at least in part, by inhibiting
      ERalpha signaling.

PMID- 21069739
TI  - COUP-TFII switches responses of venous endothelium to atherosclerotic factors
      through controlling the profile of various inherent genes expression.
AB  - Endothelial cells of arteries (AEC) have a strikingly greater responsiveness to
      atherosclerosis factors than venous endothelial cells (VEC). However, the reasons
      for this phenomenon remain unclear. Chicken ovalbumin upstream promoter
      transcription factor II (COUP-TFII) plays an important role in regulating
      embryonic arterial-venous differentiation. We therefore investigate whether COUP
      TFII is related to this different susceptibility between AEC and VEC. It is first
      confirmed that COUP-TFII is expressed in VEC but not in AEC in the adult. Using a
      siRNA strategy, we identified the expression of Jagged1 and Notch1 in cultured
      human VEC, which usually exist only in AEC, after knocking down of COUP-TFII. To
      further elucidate the role of COUP-TFII, we performed DNA microarrays in VEC
      transfected with the siRNA of COUP-TFII and subsequently stimulated with
      angiotensin II (AngII) and compared the expression profiles of 112 genes involved
      in various atherosclerosis-related pathways. The results indicated that
      expression of atherogenic genes was significantly upregulated after AngII
      stimulation in VEC transfected with COUP-TFII siRNA. Moreover, in vitro cell
      functional assay showed that knockdown of COUP-TFII in VEC increased not only
      basal but also AngII-induced cell adhesions. These results demonstrate that COUP
      TFII suppresses the susceptibility of VEC to atherosclerosis through controlling
      the expression of various atherosclerosis-related molecules.

PMID- 21069746
TI  - Schnurri-2 deficiency counteracts against bone loss induced by ovariectomy.
AB  - Schnurri (Shn)-2 is a transcriptional modulator of bone formation and bone
      resorption and its deficiency causes low turnover state with higher cancellous
      bone mass due to the defects in osteoclasts that exceeds the defects in
      osteoblasts in mice. We addressed whether such low turnover of bone remodeling in
      Shn2 deficiency may be modulated in the absence of estrogen that induces high
      turnover state in vivo. Ovariectomy reduced bone mass in wild type compared to
      sham operated control mice and such reduction in bone mass was also observed in
      Shn2 deficient mice. However, due to the high levels of basal bone mass in Shn2
      deficient mice, the bone mass levels after ovariectomy were still comparable to
      sham operated wild-type mice. Analysis indicated that estrogen depletion
      increased bone resorption at similar levels in wild type and Shn2 deficient mice
      though the basal levels of osteoclast number was slightly lower in Shn2-deficient
      mice. In contrast, basal levels of bone marrow cell mineralization in cultures
      were low in Shn2-deficeint mice while estrogen depletion increased the
      mineralization levels to those that were comparable to sham wild type. This
      indicates that Shn2-deficient mice maintain bone mass at the levels comparable to
      wild-type sham mice even after ovariectomy-induced bone loss and this correlates
      with the high levels of mineralization activity in bone marrow cells after
      ovariectomy.

PMID- 21069749
TI  - A new subclade of mtDNA haplogroup C1 found in Icelanders: evidence of pre
      Columbian contact?
AB  - Although most mtDNA lineages observed in contemporary Icelanders can be traced to
      neighboring populations in the British Isles and Scandinavia, one may have a more
      distant origin. This lineage belongs to haplogroup C1, one of a handful that was
      involved in the settlement of the Americas around 14,000 years ago. Contrary to
      an initial assumption that this lineage was a recent arrival, preliminary
      genealogical analyses revealed that the C1 lineage was present in the Icelandic
      mtDNA pool at least 300 years ago. This raised the intriguing possibility that
      the Icelandic C1 lineage could be traced to Viking voyages to the Americas that
      commenced in the 10th century. In an attempt to shed further light on the entry
      date of the C1 lineage into the Icelandic mtDNA pool and its geographical origin,
      we used the deCODE Genetics genealogical database to identify additional
      matrilineal ancestors that carry the C1 lineage and then sequenced the complete
      mtDNA genome of 11 contemporary C1 carriers from four different matrilines. Our
      results indicate a latest possible arrival date in Iceland of just prior to 1700
      and a likely arrival date centuries earlier. Most surprisingly, we demonstrate
      that the Icelandic C1 lineage does not belong to any of the four known Native
      American (C1b, C1c, and C1d) or Asian (C1a) subclades of haplogroup C1. Rather,
      it is presently the only known member of a new subclade, C1e. While a Native
      American origin seems most likely for C1e, an Asian or European origin cannot be
      ruled out.

PMID- 21069748
TI  - Mitochondrial fission and cristae disruption increase the response of cell models
      of Huntington's disease to apoptotic stimuli.
AB  - Huntington's disease (HD), a genetic neurodegenerative disease caused by a
      polyglutamine expansion in the Huntingtin (Htt) protein, is accompanied by
      multiple mitochondrial alterations. Here, we show that mitochondrial
      fragmentation and cristae alterations characterize cellular models of HD and
      participate in their increased susceptibility to apoptosis. In HD cells, the
      increased basal activity of the phosphatase calcineurin dephosphorylates the pro
      fission dynamin related protein 1 (Drp1), increasing its mitochondrial
      translocation and activation, and ultimately leading to fragmentation of the
      organelle. The fragmented HD mitochondria are characterized by cristae
      alterations that are aggravated by apoptotic stimulation. A genetic analysis
      indicates that correction of mitochondrial elongation is not sufficient to rescue
      the increased cytochrome c release and cell death observed in HD cells.
      Conversely, the increased apoptosis can be corrected by manoeuvres that prevent
      fission and cristae remodelling. In conclusion, the cristae remodelling of the
      fragmented HD mitochondria contributes to their hypersensitivity to apoptosis.

PMID- 21069752
TI  - Facial bristle feather histology and morphology in New Zealand birds:
      implications for function.
AB  - Knowledge of structure in biology may help inform hypotheses about function.
      Little is known about the histological structure or the function of avian facial
      bristle feathers. Here we provide information on morphology and histology, with
      inferences for function, of bristles in five predominantly insectivorous birds
      from New Zealand. We chose species with differing ecologies, including: brown
      kiwi (Apteryx mantelli), morepork (Ninox novaezealandae), hihi (Notiomystis
      cincta), New Zealand robin (Petroica australis), and New Zealand fantail
      (Rhipidura fuliginosa). Average bristle length corrected for body size was
      similar across species. Bristles occurred in distinct groups on different parts
      of the head and upper rictal bristles were generally longest. The lower rictal
      bristles of the fantail were the longest possessed by that species and were long
      compared to bristles of other species. Kiwi were the only species with forehead
      bristles, similar in length to the upper rictal bristles of other species, and
      the lower rictal bristles of fantails. Herbst corpuscles (vibration and pressure
      sensitive mechanoreceptors) were found in association with bristle follicles in
      all species. Nocturnal and hole-nesting birds had more heavily encapsulated
      corpuscles than diurnal open-nesting species. Our results suggest that avian
      facial bristles generally have a tactile function in both nocturnal and diurnal
      species, perhaps playing a role in prey handling, gathering information during
      flight, navigating in nest cavities and on the ground at night and possibly in
      prey-detection. These differing roles may help explain the observed differences
      in capsule thickness of the corpuscles.

PMID- 21069754
TI  - Photoluminescent smart hydrogels with reversible and linear thermoresponses.

PMID- 21069755
TI  - Self-limited oxidation: a route to form graphene layers from graphite by one-step
      heating.

PMID- 21069756
TI  - Structural and electronic properties of extremely long perylene bisimide
      nanofibers formed through a stoichiometrically mismatched, hydrogen-bonded
      complexation.
AB  - Extremely long nanofibers, whose lengths reach the millimeter regime, are
      generated via co-aggregation of a melamine-appended perylene bisimide
      semiconductor and a substituted cyanurate, both of which are ditopic triple
      hydrogen-bonding building blocks; they co-aggregate in an unexpected
      stoichiometrically mismatched 1:2 ratio. Various microscopic and X-ray
      diffraction studies suggest that hydrogen-bonded polymeric chains are formed
      along the long axis of the nanofibers by the 1:2 complexation of the two
      components, which further stack along the short axis of the nanofibers. The
      photocarrier generation mechanism in the nanofibers is investigated by time-of
      flight (TOF) experiments under electric and magnetic fields, revealing the birth
      and efficient recombination of singlet geminate electron-hole pairs. Flash
      photolysis time-resolved microwave conductivity (FP-TRMC) measurements revealed
      intrinsic 1D electron mobilities up to 0.6 cm(2) V(-1) s(-1) within nanofibers.

PMID- 21069757
TI  - Gd-labeled microparticles in MRI: in vivo imaging of microparticles after
      intraperitoneal injection.

PMID- 21069759
TI  - Enhanced charge injection in pentacene field-effect transistors with graphene
      electrodes.

PMID- 21069767
TI  - Morphology and ultrastructure of the nephridial system of Hypania invalida
      (Grube, 1860) (Annelida, Polychaeta, Ampharetidae).
AB  - The excretory organs of the freshwater polychaete Hypania invalida have been
      examined using scanning and transmission electron microscopy. Three pairs of
      macroscopically and ultrastructurally different nephridia are present in the
      thorax. Intersegmental septa in the thorax are absent, with the exception of a
      single diaphragm between second and third chaetiger. The first pair of nephridia
      is anterior to this septum, the second pair crosses the septum, with the
      nephrostomes anterior and the ducts and the nephridiopori posterior to it, and
      the third pair of nephridia is entirely posterior to the diaphragm. The first two
      pairs of nephridia have ciliated nephrostomes of moderate size and long
      nephridial ducts that extend the length of the thorax. In contrast, the third
      pair is characterized by short ducts and very prominent nephrostomes.
      Macroscopically, seven different sections of nephridial duct cells can be
      distinguished along the length of the first two pairs of nephridia, whereas, on
      an ultrastructural basis, only six different regions can be identified. Only two
      regions of different duct cells can be recognized in the third pair of nephridia.
      Cells of the two anterior pairs of nephridia show typical characteristics of
      transport epithelia and most likely function as excretory organs. In contrast,
      the duct cells of the third pair are not that much differentiated and might
      primarily be responsible for the release of sexual products, as sperm was
      observed passing through these ducts. Podocyte-like cells were observed to
      accompany nephridial ducts.

PMID- 21069770
TI  - Continuity in health care: lessons from supply chain management.
AB  - In health care, multidisciplinary collaboration is both indispensable and
      complicated. We discuss organizational problems that occur in situations where
      multiple health care providers are required to cooperate for patients with
      complex needs. Four problem categories, labelled as communication, patient
      safety, waiting times and integration are distinguished. Then we develop a supply
      chain perspective on these problems in the sense of discussing remedies according
      to supply chain management (SCM) literature. This perspective implies a business
      focus on inter-organizational conditions and requirements necessary for
      delivering health care and cure across organizational borders. We conclude by
      presenting some strategic and policy recommendations.

PMID- 21069771
TI  - Stewardship of the Spanish national health system.
AB  - Along with resource generation, financing, and health service delivery,
      stewardship is a key health system function. However, very little empirical
      analysis has been carried out on it. This paper aims to fill this gap in the
      literature by assessing the Ministry of Health's (MoHs) role as a steward of the
      Spanish National Health System (NHS) after the 2001 decentralization reform of
      health care management to the Autonomous Communities. We use the following
      stewardship framework with six sub-functions for the analysis, looking at the
      MoH's ability to: (1) formulate strategic policy framework; 2) ensure a fit
      between policy objectives and organizational structure and culture; (3) ensure
      tools for implementation; (4) build coalitions and partnerships; (5) generate
      intelligence, and (6) ensure accountability. We describe the stewardship
      function, identify existing challenges and issues in the Spanish case, and
      reflect upon methodological aspects of this exercise. We use reports, documents,
      articles, and official statistics to complete the analysis. Overall, we find the
      MoH to give an average performance in its role as the steward of the health
      system. The MoH has progressed particularly well in generating intelligence as
      well as formulating a strategic policy framework over recent years. However, it
      lacks the appropriate authority to efficiently coordinate the health system and
      to ensure that the Autonomous Communities implement policies that are in-line
      with overall NHS objectives.

PMID- 21069772
TI  - Morphology of the female reproductive system of European pea crabs (Crustacea,
      Decapoda, Brachyura, Pinnotheridae).
AB  - Commensal pea crabs inhabiting bivalves have a high reproductive output due to
      the extension andfecundity of the ovary. We studied the underlying morphology of
      the female reproductive system in the Pinnotheridae Pinnotheres pisum,
      Pinnotheres pectunculi and Nepinnotheres pinnotheres using light microscopy and
      transmission electron microscopy (TEM). Eubrachyura have internal fertilization:
      the paired vaginas enlarge into storage structures, the spermathecae, which are
      connected to the ovaries by oviducts. Sperm is stored inside the spermathecae
      until the oocytes are mature. The oocytes are transported by oviducts into the
      spermathecae where fertilization takes place. In the investigated pinnotherids,
      the vagina is of the "concave pattern" (sensu Hartnoll1968): musculature is
      attached alongside flexible parts of the vagina wall that controls the dimension
      of its lumen. The genital opening is closed by a muscular mobile operculum. The
      spermatheca can be divided into two distinct regions by function and morphology.
      The ventral part includes the connection with vagina and oviduct and is regarded
      as the zone where fertilization takes place. It is lined with cuticle except
      where the oviduct enters the spermatheca by the "holocrine transfer tissue." At
      ovulation, the oocytes have to pass through this multilayered glandular
      epithelium performing holocrine secretion. The dorsal part of the spermatheca is
      considered as the main sperm storage area. It is lined by a highly secretory
      apocrine glandular epithelium. Thus, two different forms of secretion occur in
      the spermathecae of pinnotherids. The definite role of secretion in sperm storage
      and fertilization is not yet resolved, but it is notable that structure and
      function of spermathecal secretion are more complex in pinnotherids, and probably
      more efficient, than in other brachyuran crabs.

PMID- 21069779
TI  - Postnatal alterations in induction threshold and expression magnitude of long
      term potentiation and long-term depression at hippocampal synapses.
AB  - Activity-dependent synaptic plasticity refines neural networks during development
      and subserves information processing in adulthood. Previous research has revealed
      postnatal alterations in synaptic plasticity at nearly all forebrain synapses,
      suggesting different forms of synaptic plasticity may contribute to network
      development and information processing. To assess possible relationships between
      modifications in synaptic plasticity and maturation of cognitive ability, we
      examined excitatory synaptic function in area CA1 of the mouse hippocampus ~3
      weeks of age, when hippocampal-dependent learning and memory abilities first
      emerge. Long-term potentiation (LTP) and depression (LTD) of synaptic efficacy
      were observed in slices from juvenile animals younger than 3 weeks of age. Both
      pre- and postsynaptic mechanisms supported LTP and LTD in juveniles. After the
      third postnatal week, the magnitude of LTP was reduced and the threshold for
      postsynaptic induction was reduced, but the threshold for presynaptic induction
      was increased. The reduced threshold for postsynaptic LTP appeared to be due,
      partly, to an increase in baseline excitatory synaptic strength, which likely
      permitted greater postsynaptic depolarization during induction. Low frequency
      stimulation did not induce LTD at this more mature stage, but it blocked
      subsequent induction of LTP, suggesting metaplastic differences across age
      groups. Late postnatal modifications in activity-dependent synaptic plasticity
      might reflect attenuation of mechanisms more closely tied to network formation
      (presynaptic potentiation and pre- and postsynaptic depression) and unmasking of
      mechanisms underlying information processing and storage (associative
      postsynaptic potentiation), which likely impact the integrative capacity of the
      network and regulate the emergence of adult-like cognitive abilities.

PMID- 21069780
TI  - Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a
      mouse model of Alzheimer disease.
AB  - Alzheimer's disease (AD) and ageing are associated with impaired learning and
      memory, and recent findings point toward modulating chromatin remodeling through
      histone acetylation as a promising therapeutic strategy. Here we report that
      systemic administration of the HDAC inhibitor 4-phenylbutyrate (PBA) reinstated
      fear learning in the Tg2576 mouse model of AD. Tg2576 mice develop age-dependent
      amyloid pathology and cognitive decline that closely mimics disease progression
      in humans. Memory reinstatement by PBA was observed independently of the disease
      stage: both in 6-month-old Tg2576 mice, at the onset of the first symptoms, but
      also in aged, 12- to 16-month-old mice, when amyloid plaque deposition and major
      synaptic loss has occurred. Reversal of learning deficits was associated to a PBA
      induced clearance of intraneuronal Abeta accumulation, which was accompanied by
      mitigation of endoplasmic reticulum (ER) stress, and to restoration of dendritic
      spine densities of hippocampal CA1 pyramidal neurons to control levels.
      Furthermore, the expression of plasticity-related proteins such as the NMDA
      receptor subunit NR2B and the synaptic scaffold SAP102 was significantly
      increased by PBA. Our data suggest that the beneficial effects of PBA in memory
      are mediated both via its chemical chaperone-like activity and via the
      transcriptional activation of a cluster of proteins required for the induction of
      synaptic plasticity and structural remodeling.

PMID- 21069782
TI  - Right-hemispheric dominance of spatial memory in split-brain mice.
AB  - Left-right asymmetry of human brain function has been known for a century,
      although much of molecular and cellular basis of brain laterality remains to be
      elusive. Recent studies suggest that hippocampal CA3-CA1 excitatory synapses are
      asymmetrically arranged, however, the functional implication of the asymmetrical
      circuitry has not been studied at the behavioral level. In order to address the
      left-right asymmetry of hippocampal function in behaving mice, we analyzed the
      performance of "split-brain" mice in the Barnes maze. The "split-brain" mice
      received ventral hippocampal commissure and corpus callosum transection in
      addition to deprivation of visual input from one eye. In such mice, the
      hippocampus in the side of visual deprivation receives sensory-driven input.
      Better spatial task performance was achieved by the mice which were forced to use
      the right hippocampus than those which were forced to use the left hippocampus.
      In two-choice spatial maze, forced usage of left hippocampus resulted in a
      comparable performance to the right counterpart, suggesting that both hippocampal
      hemispheres are capable of conducting spatial learning. Therefore, the results
      obtained from the Barnes maze suggest that the usage of the right hippocampus
      improves the accuracy of spatial memory. Performance of non-spatial yet
      hippocampus-dependent tasks (e.g. fear conditioning) was not influenced by the
      laterality of the hippocampus.

PMID- 21069783
TI  - Regulation of hippocampal long-term potentiation and long-term depression by
      diacylglycerol kinase zeta.
AB  - Diacylglycerol (DAG) is an important signaling molecule at neuronal synapses.
      Generation of synaptic DAG is triggered by the activation of diverse surface
      receptors including N-methyl-D-aspartate (NMDA) receptors and metabotropic
      glutamate receptors. The action of DAG is terminated by enzymatic conversion of
      DAG to phosphatidic acid (PA) by DAG kinases (DGKs). DGKzeta, one of many
      mammalian DGKs, is localized to synapses through direct interaction with the
      postsynaptic scaffolding protein PSD-95, and regulates dendritic spine
      maintenance by promoting DAG-to-PA conversion. However, a role for DGKzeta in the
      regulation of synaptic plasticity has not been explored. We report here that
      Schaffer collateral-CA1 pyramidal synapses in the hippocampus of DGKzeta-knockout
      (DGKzeta(-/-) ) mice show enhanced long-term potentiation (LTP) and attenuated
      long-term depression (LTD). The attenuated LTD at DGKzeta(-/-) synapses involves
      both NMDA receptors and metabotropic glutamate receptors. These changes in LTP
      and LTD were reversed by phospholipase C inhibition, which blocks DAG production.
      Similar reversals in both LTP and LTD were also induced by inhibition of protein
      kinase C, which acts downstream of DAG. These results suggest that DGKzeta
      regulates hippocampal LTP and LTD by promoting DAG-to-PA conversion, and
      establish that phospholipase C and protein kinase C lie upstream and downstream,
      respectively, of DGKzeta-dependent regulation of hippocampal LTP and LTD.

PMID- 21069781
TI  - A novel non-CB1/TRPV1 endocannabinoid-mediated mechanism depresses excitatory
      synapses on hippocampal CA1 interneurons.
AB  - Endocannabinoids (eCBs) mediate various forms of synaptic plasticity at
      excitatory and inhibitory synapses in the brain. The eCB anandamide binds to
      several receptors including the transient receptor potential vanilloid 1 (TRPV1)
      and cannabinoid receptor 1 (CB1). We recently identified that TRPV1 is required
      for long-term depression at excitatory synapses on CA1 hippocampal stratum
      radiatum interneurons. Here we performed whole-cell patch clamp recordings from
      CA1 stratum radiatum interneurons in rat brain slices to investigate the effect
      of the eCB anandamide on excitatory synapses as well as the involvement of Group
      I metabotropic glutamate receptors (mGluRs), which have been reported to produce
      eCBs endogenously. Application of the nonhydrolysable anandamide analog R
      methanandamide depressed excitatory transmission to CA1 stratum radiatum
      interneurons by ~50%. The Group I mGluR agonist DHPG also depressed excitatory
      glutamatergic transmission onto interneurons to a similar degree, and this
      depression was blocked by the mGluR5 antagonist MPEP (10 MUM) but not by the
      mGluR1 antagonist CPCCOEt (50 MUM). Interestingly, however, neither DHPG-mediated
      nor R-methanandamide-mediated depression was blocked by the TRPV1 antagonist
      capsazepine (10 MUM), the CB1 antagonist AM-251 (2 MUM) or a combination of both,
      suggesting the presence of a novel eCB receptor or anandamide target at
      excitatory hippocampal synapses. DHPG also occluded R-methanandamide depression,
      suggesting the possibility that the two drugs elicit synaptic depression via a
      shared signaling mechanism. Collectively, this study illustrates a novel
      CB1/TRPV1-independent eCB pathway present in the hippocampus that mediates
      depression at excitatory synapses on CA1 stratum radiatum interneurons.

PMID- 21069786
TI  - The dual role of HLXB9 in leukemia.
AB  - BACKGROUND: The HLXB9 gene encodes a homeodomain containing transcription factor
      which has been implicated in the development of both solid and hematological
      malignancies. In leukemia it is one of the two fused genes, along with ETV6, in a
      recurrent translocation frequently observed in infant AML. PROCEDURE: Here we
      investigate the role of epigenetic inactivation of the HLXB9 gene in leukemia.
      Quantitative DNA methylation analysis was performed using the COBRA assay, and
      qRT-PCR was used to assess the effects of methylation on expression in
      hematological cell lines and primary ALL samples. RESULTS: Hypermethylation of
      the HLXB9 gene was found to be a frequent event in childhood ALL, occurring in
      33% of cases. However, it was rarely or never observed in other types of
      leukemia, including AML, CML, and CLL, with the exception of adult ALL, in which
      39% of cases were hypermethylated. Furthermore, hypermethylation of HLXB9 results
      in loss of expression in hematological cell lines and primary ALL samples.
      CONCLUSION: These results suggest that HLXB9 may have a dual role in childhood
      leukemia, as an oncogene in infant AML but as a tumor suppressor in childhood
      ALL.

PMID- 21069788
TI  - NOMPC, a member of the TRP channel family, localizes to the tubular body and
      distal cilium of Drosophila campaniform and chordotonal receptor cells.
AB  - Mechanoreception underlies the senses of touch, hearing and balance. An early
      event in mechanoreception is the opening of ion channels in response to
      mechanical force impinging on the cell. Here, we report antibody localization of
      NOMPC, a member of the transient receptor potential (TRP) ion channel family, to
      the tubular body of campaniform receptors in the halteres and to the distal
      regions of the cilia of chordotonal neurons in Johnston's organ, the sound
      sensing organ of flies. Because NOMPC has been shown to be associated with the
      mechanotransduction process, our studies suggest that the transduction apparatus
      in both types of sensory cells is located in regions where a specialized
      microtubule-based cytoskeleton is in close proximity to an overlying cuticular
      structure. This localization suggests a transmission route of the mechanical
      stimulus to the cell. Furthermore, the commonality of NOMPC locations in the two
      structurally different receptor types suggests a conserved transduction apparatus
      involving both the intracellular cytoskeleton and the extracellular matrix.

PMID- 21069796
TI  - Interactive segmentation of clustered cells via geodesic commute distance and
      constrained density weighted Nystrom method.
AB  - An interactive method is proposed for complex cell segmentation, in particular of
      clustered cells. This article has two main contributions: First, we explore a
      hybrid combination of the random walk and the geodesic graph based methods for
      image segmentation and propose the novel concept of geodesic commute distance to
      classify pixels. The computation of geodesic commute distance requires an
      eigenvector decomposition of the weighted Laplacian matrix of a graph constructed
      from the image to be segmented. Second, by incorporating pairwise constraints
      from seeds into the algorithm, we present a novel method for eigenvector
      decomposition, namely a constrained density weighted Nystrom method. Both visual
      and quantitative comparison with other semiautomatic algorithms including Voronoi
      based segmentation, grow cut, graph cuts, random walk, and geodesic method are
      given to evaluate the performance of the proposed method, which is a powerful
      tool for quantitative analysis of clustered cell images in live cell imaging.

PMID- 21069797
TI  - The pre-ovulatory luteinizing hormone surge is followed by down-regulation of
      CYP19A1, HSD3B1, and CYP17A1 and chromatin condensation of the corresponding
      promoters in bovine follicles.
AB  - The pre-ovulatory luteinizing hormone (LH) surge induces an extensive molecular,
      physiological, and morphological reorganization of the bovine follicle. This
      study was designed to elucidate if chromatin modulation is involved in the LH
      induced gene regulation. Granulosa and theca of well-characterized large bovine
      follicles were isolated before and after the LH surge. CYP19A1, HSD3B1, and
      CYP17A1 transcripts, which encode key enzymes of steroid hormone biosynthesis,
      were quantified by real-time PCR (qPCR) and the degree of chromatin condensation
      was determined by DNase I protection assays. After LH, granulosa-specific CYP19A1
      and theca-specific CYP17A1 transcripts were almost completely down-regulated.
      Also, the abundance of HSD3B1 transcripts was reduced. The promoter chromatin of
      HSD3B1 and particularly of CYP19A1 was significantly less accessible to DNAse I
      in both cell types after LH, whereas the chromatin accessibility of the CYP17A1
      promoter changed only in the theca. Correlation analysis revealed partly, highly
      significant negative correlations between transcript abundance and protection
      from DNase I digestion of the corresponding chromatin. The data strongly suggest
      that LH induces cell type- and gene-specific chromatin condensation in the pre
      ovulatory bovine follicle. This epigenetic mechanism might be involved in the pre
      ovulatory down-regulation of genes.

PMID- 21069801
TI  - Rotational atherectomy with drug-eluting stents: a necessary technique in the
      current era.

PMID- 21069807
TI  - Reduced levels of folate transporters (PCFT and RFC) in membrane lipid rafts
      result in colonic folate malabsorption in chronic alcoholism.
AB  - We studied the effect of chronic ethanol ingestion on folate transport across the
      colonic apical membranes (CAM) in rats. Male Wistar rats were fed 1 g/kg body
      weight/day ethanol (20%) solution orally for 3 months and folate transport was
      studied in the isolated colon apical membrane vesicles. The folate transport was
      found to be carrier mediated, saturable, with pH optima at 5.0. Chronic ethanol
      ingestion reduced the folate transport across the CAM by decreasing the affinity
      of transporters (high Km) for the substrate and by decreasing the number of
      transporter molecules (low Vmax) on the colon luminal surface. The decreased
      transport activity at the CAM was associated with down-regulation of the proton
      coupled folate transporter (PCFT) and the reduced folate carrier (RFC) which
      resulted in decreased PCFT and RFC protein levels in the colon of rats fed
      alcohol chronically. Moreover, the PCFT and the RFC were found to be distributed
      in detergent insoluble fraction of the CAM in rats. Floatation experiments on
      Optiprep density gradients demonstrated the association of the PCFT and the RFC
      protein with lipid rafts (LR). Chronic alcoholism decreased the PCFT and the RFC
      protein levels in the CAM LR in accordance with the decreased synthesis. Hence,
      we propose that downregulation in the expression of the PCFT and the RFC in colon
      results in reduced levels of these transporters in colon apical membrane LR as a
      mechanism of folate malabsorption during chronic alcoholism.

PMID- 21069809
TI  - Adiponectin induces interleukin-6 production and its underlying mechanism in
      adult rat cardiac fibroblasts.
AB  - It has been reported that adiponectin enhances interleukin-6 (IL-6) production in
      cardiac fibroblasts derived from neonatal rats and adult mice, but the mechanisms
      involved remain unknown. In the present study, we explored the effect and
      mechanisms of adiponectin on IL-6 production in adult rat cardiac fibroblasts.
      Globular adiponectin (gAd) increased IL-6 mRNA expression and protein secretion
      in cultured adult rat cardiac fibroblasts. gAd-induced IL-6 release was
      attenuated after RNA interference inhibition of adiponectin receptor 1 (AdipoR1),
      but not AdipoR2 or an adaptor protein APPL1. gAd increased the phosphorylation of
      AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase
      (p38MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun-N
      terminal kinase (JNK). Inhibitors of AMPK (araA), p38MAPK (SB202190), and ERK1/2
      (PD98059 and U0126) but not JNK (SP600125) suppressed gAd-induced IL-6
      production. In transient transfection assays of IL-6 promoter/luciferase reporter
      plasmids, gAd increased the transcriptional activity of the full-length IL-6
      promoter. Deletion analysis of the IL-6 promoter indicated that activator protein
      1 (AP-1), nuclear factor for IL-6 (NF-IL-6) and nuclear factor kappaB (NF-kappaB)
      binding sites were important for gAd-induced IL-6 transcription. Our data suggest
      that gAd enhances IL-6 synthesis and release in adult rat cardiac fibroblasts
      through AdipoR1. Activation of AMPK, p38MAPK, and ERK1/2 mediates the
      intracellular signal transduction. AP-1, NF-IL-6, and NF-kappaB cis-elements are
      required for gAd-induced IL-6 transcription.

PMID- 21069823
TI  - Xenopus er71 is involved in vascular development.
AB  - Vasculogenesis and hematopoiesis are closely linked in developing vertebrates.
      Recently, the existence of a common progenitor of these two tissues, the
      hemangioblast, has been demonstrated in different organisms. In Xenopus early
      vascular and hematopoietic cells differentiate in a region called the anterior
      ventral blood island (aVBI). Differentiating cells from this region migrate out
      to form embryonic blood and part of the vascular structures of the early frog
      embryo. A number of members of the ETS family of transcription factors are
      expressed in endothelial cells and some of them play important roles at various
      stages of vascular development. The loss of ER71 function in mice led to a
      complete loss of blood and vascular structures. Similarly, knock down of the
      zebrafish homolog of er71, etsrp, greatly affected development of vascular
      structures and myeloid cells. We have identified the Xenopus ortholog of er71 and
      could show that er71 function in Xenopus is required for vasculogenesis, but not
      for the development of hematopoietic cells.

PMID- 21069828
TI  - Tissue- and development-dependent expression of the small GTPase Arf6 in mice.
AB  - The small GTPase Arf6 is a member of the Arf (ADP-ribosylation factor) family.
      Although the function of Arf6 has been heavily studied at the cellular level, its
      physiological function at the whole animal level is largely unknown. In this
      study, we examined both the tissue distribution and developmental timing of Arf6
      expression in wild type mice to obtain valuable information to speculate on the
      physiological function of Arf6. Western blot analysis using anti-Arf6 antibody
      revealed that Arf6 was ubiquitously expressed with its developmental timing
      differing in a tissue-specific manner. These results were supported by Arf6 mRNA
      in situ hybridization experiments, which showed that Arf6 was highly expressed in
      the polarized epithelial cells and embryonic mesenchymal cells of most tissues in
      a temporally dependent manner. Taken in toto, our results suggest that the
      expression of Arf6 in mouse tissues is precisely regulated in a development- and
      tissue-dependent manner.

PMID- 21069829
TI  - Nucleotide exchange factor RIC-8 is indispensable in mammalian early development.
AB  - The guanine nucleotide exchange factor RIC-8 is a conserved protein essential for
      the asymmetric division in the early embryogenesis in different organisms. The
      function of RIC-8 in mammalian development is not characterized so far. In this
      study we map the expression of RIC-8 during the early development of mouse. To
      elucidate the RIC-8 function we used Ric-8(-/-) mutant embryos. The Ric-8(-/-)
      embryos reach the gastrulation stage but do not develop further and die at E6.5
      E8.5. We characterized the Ric-8(-/-) embryonic phenotype by morphological and
      marker gene analyses. The gastrulation is initiated in Ric-8(-/-) embryos but
      their growth is retarded, epiblast and mesoderm disorganized. Additionally, the
      basement membrane is defective, amnion folding and the formation of allantois are
      interfered, also the cavitation. Furthermore, the orientation of the Ric-8(-/-)
      embryo in the uterus was abnormal. Our study reveals that the activity of RIC-8
      protein is irreplaceable for the correct gastrulation of mouse embryo.

PMID- 21069826
TI  - Microarray identification of novel downstream targets of FoxD4L1/D5, a critical
      component of the neural ectodermal transcriptional network.
AB  - FoxD4L1/D5 is a forkhead transcription factor that functions as both a
      transcriptional activator and repressor. FoxD4L1/D5 acts upstream of several
      other neural transcription factors to maintain neural fate, regulate neural plate
      patterning, and delay the expression of neural differentiation factors. To
      identify a more complete list of downstream genes that participate in these
      earliest steps of neural ectodermal development, we carried out a microarray
      analysis comparing gene expression in control animal cap ectodermal explants
      (ACs), which will form epidermis, to that in FoxD4L1/D5-expressing ACs. Forty
      four genes were tested for validation by RT-PCR of ACs and/or in situ
      hybridization assays in embryos; 86% of those genes up-regulated and 100% of
      those genes down-regulated in the microarray were altered accordingly in one of
      these independent assays. Eleven of these 44 genes are of unknown function, and
      we provide herein their developmental expression patterns to begin to reveal
      their roles in ectodermal development.

PMID- 21069830
TI  - Core fucosylation is required for midline patterning during zebrafish
      development.
AB  - Complex carbohydrates represent one of the most polymorphic classes of
      macromolecules, but their functions during embryonic development remain poorly
      defined. Herein, we show that knockdown of FucT8, the fucosyltransferase
      responsible for adding an alpha1,6 fucosyl residue to the core region of N-linked
      oligosaccharides, results in defective midline patterning during zebrafish
      development. Reduced FucT8 expression leads to mild cyclopia, small forebrains, U
      shaped somites, among other midline patterning defects. One of the principal
      FucT8 substrates was identified as Apolipoprotein B (ApoB), the major scaffold
      protein that is responsible for assembly and secretion of lipoprotein particles
      in vertebrates. In Drosophila, lipoprotein particles are thought to facilitate
      cell signaling by serving as a transport vehicle for lipid-modified cell
      signaling proteins, such as hedgehog. In this regard, knockdown of ApoB
      expression in zebrafish embryos leads to similar midline patterning defects as
      those seen in FucT8 morphant embryos. Furthermore, preliminary studies suggest
      that ApoB facilitates Sonic hedgehog signaling during zebrafish development,
      analogous to the function of lipoprotein particles during hedgehog signaling in
      Drosophila.

PMID- 21069831
TI  - Primer and interviews: molecular mechanisms of morphological evolution.
AB  - The beauty of the developing embryo, and the awe that it inspires, lure many
      scientists into the field of developmental biology. What compels cells to divide,
      migrate, and morph into a being with a complex body plan? Evolutionary
      developmental biologists hold similar fascinations, with dynamics that take place
      on a grander timescale. How do phenotypic traits diverge over evolutionary time?
      This primer illustrates how a deep understanding of the basic principles that
      underlie developmental biology have changed how scientists think about the
      evolution of body form. The primer culminates in a conversation with David Stern,
      PhD, and Michael Shapiro, PhD, who discuss current topics in morphological
      evolution, why the field should be of interest to classic developmental
      biologists, and what lies ahead.

PMID- 21069833
TI  - Systematic review of levodopa dose equivalency reporting in Parkinson's disease.
AB  - Interpretation of clinical trials comparing different drug regimens for
      Parkinson's disease (PD) is complicated by the different dose intensities used:
      higher doses of levodopa and, possibly, other drugs produce better symptomatic
      control but more late complications. To address this problem, conversion factors
      have been calculated for antiparkinsonian drugs that yield a total daily levodopa
      equivalent dose (LED). LED estimates vary, so we undertook a systematic review of
      studies reporting LEDs to provide standardized formulae. Electronic database and
      hand searching of references identified 56 primary reports of LED estimates. Data
      were extracted and the mean and modal LEDs calculated. This yielded a
      standardized LED for each drug, providing a useful tool to express dose intensity
      of different antiparkinsonian drug regimens on a single scale. Using these
      conversion formulae to report LEDs would improve the consistency of reporting and
      assist the interpretation of clinical trials comparing different PD medications.

PMID- 21069850
TI  - BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor
      stage and survival.
AB  - BACKGROUND: Defects in the mitotic spindle checkpoint have been proposed to
      contribute to the chromosomal instability observed in human cancers, including
      oral squamous cell carcinoma (OSCC). BUBR1 is a key component of the spindle
      checkpoint, whose role in oral carcinogenesis still needs to be clarified.
      METHODS: We have analyzed the expression of BUBR1 in 49 cases of OSCC by
      immunohistochemistry and compared the findings with clinicopathologic parameters,
      proliferative activity, and DNA ploidy. RESULTS: BUBR1 was overexpressed in 11
      cases (22.4%). Tumors with overexpression of BUBR1 were associated with a less
      advanced pathologic stage (p = .05) and showed longer survival periods (p = .38)
      but shorter recurrence-free survival periods (p = .13) than those without it.
      CONCLUSIONS: Our data imply the possibility that BUBR1 may be involved in the
      progression of OSCC, and suggest that BUBR1 may be a promising prognostic marker
      in patients with OSCC.

PMID- 21069865
TI  - Dasatinib, even at low doses, is an effective second-line therapy for chronic
      myeloid leukemia patients resistant or intolerant to imatinib. Results from a
      real life-based Italian multicenter retrospective study on 114 patients.

PMID- 21069851
TI  - Association of pituitary tumor transforming gene expression with early oral
      tumorigenesis and malignant progression of precancerous lesions.
AB  - BACKGROUND: Pituitary tumor transforming gene (PTTG1) is overexpressed in many
      types of human cancers and is involved in late-stage tumor progression. The role
      of PTTG1 in initiating tumorigenesis is unclear. METHODS: PTTG1 expression was
      assessed in precancerous lesions and squamous cell carcinomas of the oral cavity
      (OSCC). The association between the protein expression and clinicopathologic
      parameters was analyzed. The expression level of PTTG1 upon carcinogen treatment
      was also investigated. RESULTS: PTTG1 was overexpressed in both precancerous
      lesions and OSCC. The expression of PTTG1 was associated with carcinogen exposure
      in vivo and in vitro. PTTG1 overexpression was an independent factor for oral
      cancer development in precancerous lesions. CONCLUSIONS: This study provides the
      first evidence that PTTG1 is involved in the early stages of oral tumorigenesis.
      Carcinogen exposure may cause the initial induction of PTTG1 expression in oral
      precancerous lesions. PTTG1 overexpression is a potential prognosticator for
      malignant progression of oral precancerous lesions.

PMID- 21069866
TI  - An accurate feature-based method for identifying DNA-binding residues on protein
      surfaces.
AB  - Proteins that interact with DNA play vital roles in all mechanisms of gene
      expression and regulation. In order to understand these activities, it is crucial
      to analyze and identify DNA-binding residues on DNA-binding protein surfaces.
      Here, we proposed two novel features B-factor and packing density in combination
      with several conventional features to characterize the DNA-binding residues in a
      well-constructed representative dataset of 119 protein-DNA complexes from the
      Protein Data Bank (PDB). Based on the selected features, a prediction model for
      DNA-binding residues was constructed using support vector machine (SVM). The
      predictor was evaluated using a 5-fold cross validation on above dataset of 123
      DNA-binding proteins. Moreover, two independent datasets of 83 DNA-bound protein
      structures and their corresponding DNA-free forms were compiled. The B-factor and
      packing density features were statistically analyzed on these 83 pairs of holo
      apo proteins structures. Finally, we developed the SVM model to accurately
      predict DNA-binding residues on protein surface, given the DNA-free structure of
      a protein. Results showed here indicate that our method represents a significant
      improvement of previously existing approaches such as DISPLAR. The observation
      suggests that our method will be useful in studying protein-DNA interactions to
      guide consequent works such as site-directed mutagenesis and protein-DNA docking.

PMID- 21069871
TI  - Quantitative assessment of interproximal wear facet outlines for the association
      of isolated molars.
AB  - The determination of the minimum number of individuals can be very challenging,
      especially in an assemblage of fragmentary bones and isolated teeth. Similarities
      in tooth morphology, degree of wear, and interproximal wear facets (IPWF) are
      generally used to associate isolated teeth qualitatively. However, no
      quantitative method has yet been established for an objective identification and
      matching of isolated tooth crowns. In this study, we analyze the IPWF morphology
      of adjacent mandibular molars (17 M(1)/M(2) pairs), applying both qualitative and
      quantitative methods to test a reproducible approach for crown association. The
      surfaces of distal (for M(1)) and mesial (for M(2)) IPWF were surface-scanned and
      digitally selected. Three-dimensional (3D) and two-dimensional (2D) outlines of
      IPWF were analyzed using elliptic Fourier analysis (EFA) and geometric
      morphometrics methods (GMM). Additionally, teeth were qualitatively associated by
      visual evaluation of the IPWF outline and by physical matching. Unsatisfactory
      results with less than 50% of tooth pairs correctly associated were obtained by
      using both methods, shape analysis (digital approach) and the visual evaluation
      (qualitative assessment) of the IPWF outline. The physical matching of the crowns
      showed highly variable accuracy ranging between 53% and 77%. The quantitative
      form-space analysis of 2D IPWF outlines provided the best results (82% of
      correctly associated teeth), but no statistically significant differences were
      recorded when compared with the manual matching. Since three tooth pairs out of
      17 could not be quantitatively associated, we suggest that the quantitative
      analysis of IPWF should be used only in addition with other approaches.

PMID- 21069876
TI  - Technical note: a re-evaluation of stature estimation from skeletal length in the
      grave.
AB  - Several methods for stature estimation have been proposed over the years. Among
      these methods is anatomical reconstruction, regression based on long bone
      lengths, and measuring skeletal vertex - talus length in the grave for
      individuals buried in a supine position. Recent studies have dealt with the
      applicability of skeletal length in the grave (Petersen: Int J Osteoarchaeol 15
      (2005) 106-114) and anatomical reconstruction (Raxter et al.: Am J Phys Anthropol
      130 (2006) 374-384). The results from the latter study calls into question the
      results of the former study. Therefore an investigation of the potential bias of
      using skeletal length in the grave as an estimate of living stature has been
      performed. Twenty Medieval Danish skeletons were measured both in situ and in the
      laboratory, and the anatomically reconstructed stature (Raxter et al.: Am J Phys
      Anthropol 130 (2006) 374-384) was compared with the skeletal length in the grave.
      The results show that 2.5 cm should be added to skeletal length in the grave in
      order to obtain an unbiased estimate ofliving stature.

PMID- 21069870
TI  - A differential association of Apolipoprotein E isoforms with the amyloid-beta
      oligomer in solution.
AB  - The molecular pathogenesis of disorders arising from protein misfolding and
      aggregation is difficult to elucidate, involving a complex ensemble of
      intermediates, whose toxicity depends upon their state of progression along
      distinct processing pathways. To address the complex misfolding and aggregation
      that initiates the toxic cascade resulting in Alzheimer's disease (AD), we have
      developed a 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid spin
      labeled amyloid-beta (Abeta) peptide to observe its isoform-dependent interaction
      with the apoE protein. Although most individuals carry the E3 isoform of apoE,
      ~15% of humans carry the E4 isoform, which is recognized as the most significant
      genetic determinant for Alzheimer's. ApoE is consistently associated with the
      amyloid plaque marker for AD. A vital question centers on the influence of the
      two predominant isoforms, E3 and E4, on Abeta peptide processing and hence Abeta
      toxicity. We used electron paramagnetic resonance (EPR) spectroscopy of
      incorporated spin labels to investigate the interaction of apoE with the toxic
      oligomeric species of Abeta in solution. EPR spectra of the spin-labeled side
      chain report on side chain and backbone dynamics as well as the spatial proximity
      of spins in an assembly. Our results indicate oligomer binding involves the C
      terminal domain of apoE, with apoE3 reporting a much greater response through
      this conformational marker. Coupled with SPR binding measurements, apoE3 displays
      a higher affinity and capacity for the toxic Abeta oligomer. These findings
      support the hypothesis that apoE polymorphism and Alzheimer's risk can largely be
      attributed to the reduced ability of apoE4 to function as a clearance vehicle for
      the toxic form of Abeta.

PMID- 21069886
TI  - Emergent properties resulting from type-II band alignment in semiconductor
      nanoheterostructures.
AB  - The development of elegant synthetic methodologies for the preparation of
      monocomponent nanocrystalline particles has opened many possibilities for the
      preparation of heterostructured semiconductor nanostructures. Each of the
      integrated nanodomains is characterized by its individual physical properties,
      surface chemistry, and morphology, yet, these multicomponent hybrid particles
      present ideal systems for the investigation of the synergetic properties that
      arise from the material combination in a non-additive fashion. Of particular
      interest are type-II heterostructures, where the relative band alignment of their
      constituent semiconductor materials promotes a spatial separation of the electron
      and hole following photoexcitation, a highly desirable property for photovoltaic
      applications. This article highlights recent progress in both synthetic
      strategies, which allow for material and architectural modulation of novel
      nanoheterostructures, as well as the experimental work that provides insight into
      the photophysical properties of type-II heterostructures. The effects of external
      factors, such as electric fields, temperature, and solvent are explored in
      conjunction with exciton and multiexciton dynamics and charge transfer processes
      typical for type-II semiconductor heterostructures.

PMID- 21069887
TI  - On realizing higher efficiency polymer solar cells using a textured substrate
      platform.

PMID- 21069888
TI  - A new type of electrolyte with a light-trapping scheme for high-efficiency quasi
      solid-state dye-sensitized solar cells.

PMID- 21069889
TI  - A biodegradable and biocompatible regular nanopattern for large-scale selective
      cell growth.
AB  - A biodegradable substrate with a regular array of nanopillars fabricated by
      electron-beam lithography and hot embossing is used to address the mechanisms of
      nanotopographical control of cell behavior. Two different cell lines cultured on
      the nanopillars show striking differences in cell coverage. These changes are
      topography- and cell-dependent, and are not mediated by air bubbles trapped on
      the nanopattern. For the first time, a strong cell-selective effect of the same
      nanotopography has been clearly demonstrated on a large area; while fibroblast
      proliferation is inhibited, endothelial cell spreading is visibly enhanced. The
      reduced fibroblast proliferation indicates that a reduction of available surface
      area induced by nanotopography might be the main factor affecting cell growth on
      nanopatterns. The results presented herein pave the way towards the development
      of permanent vascular replacements, where non-adhesive, inert, surfaces will
      induce rapid in situ endothelialization to reduce thrombosis and occlusion.

PMID- 21069890
TI  - "Sandwich" microcontact printing as a mild route towards monodisperse Janus
      particles with tailored bifunctionality.

PMID- 21069891
TI  - Flexible replication technique for high-aspect-ratio nanostructures.
AB  - A flexible, nondestructive, and cost-effective replication technique for
      nanostructures is presented. The advantages of the process are: 1) it allows for
      tailoring structural parameters of the replica (e.g., line width) nearly
      independent of the structural geometry of the master; 2) it allows for
      replication of high-aspect-ratio structures also in polymer materials from
      solution (especially noncurable polymers) such as polystyrene and
      polymethylmethacrylate; 3) it includes an easy separation process, thus
      preserving the master for repeated use. Linear grating replicas with line widths
      ranging from 88 to 300 nm are obtained using a single nanostructured master.
      Nanofibers and complex nanopatterned replicas are achievable. The presented
      technique and its flexibility show that atomic layer deposition is a unique tool
      for the preparation of high-efficiency polarizer diffractive optics, photonics,
      electronics, and catalysts.

PMID- 21069892
TI  - Vision.  Preserving your sight as you age.

PMID- 21069893
TI  - My doctor suggested that I get more exercise.  I am considering joining a gym,
      but how can I cut costs?

PMID- 21069894
TI  - A child case of  hyper-IgE syndrome.

PMID- 21069895
TI  - Incidence of posterior vessel wall puncture during ultrasound-guided vessel
      cannulation in a simulated model.
AB  - OBJECTIVES: The incidence of posterior vessel wall puncture (PVWP) during central
      line placement with possible subsequent injury to structures lying behind the
      vein is unknown. At times the internal jugular vein lies immediately anterior to
      the carotid artery rather than lateral to it, leading to potential arterial
      puncture should the needle pass through the vein completely. The objective of
      this study is to evaluate the incidence of PVWP during simulated ultrasound (US)
      guided vessel cannulation. METHODS: Enrolled subjects were emergency medicine
      resident and attending physicians. Subjects performed US-guided venous access on
      simulated blood vessels within gelatin-based US phantoms. While blinded to the
      purpose of the study, each subject performed successful cannulation of the vessel
      on separate phantoms, with wire placement confirmed by expert review of a follow
      up US. Each phantom was subsequently deconstructed to manually inspect for PVWP.
      RESULTS: Thirty-five subjects with a range of experience in the technique
      participated, each performing both transverse and long-axis approaches for a
      total of 70 cannulations. The overall incidence of PVWP was 34% (95% confidence
      interval [CI] = 22.9% to 45.1%). CONCLUSIONS: This study found a high incidence
      of inadvertent PVWP during simulated US-guided vessel cannulation in this model.

PMID- 21069896
TI  - A virtual reality simulation curriculum for intravenous cannulation training.
AB  - OBJECTIVES: Although virtual reality (VR) simulators play an important role in
      modern medical training, their efficacy is not often evaluated using learning
      curves. In this study, the learning curves of novice and intermediate users were
      elicited during a VR simulation-based curriculum for intravenous (IV)
      cannulation. METHODS: This was a prospective observational study of subjects
      undergoing training using a VR model of IV cannulation. Participants were divided
      into two groups: novices (third-year medical students with no prior practical
      experience in IV catheterization) and intermediates (recent graduates with
      limited experience). Performance was measured with two endpoints: time to
      completion and errors committed. Errors were categorized as critical or
      noncritical. Learning curves (error score and time completion vs. session number)
      were analyzed using the Friedman's test. Performance before and after training
      was compared using the Kruskal-Wallis test. The Spearman rank correlation
      coefficient (r(s)) was used to determine the correlation between time completion
      and error score estimates. The number of attempts required to complete the
      training phase was also measured and compared between the two groups. RESULTS:
      Thirty subjects were enrolled: 17 in the novice group and 13 in the intermediate
      group. Learning curve plateaus of intermediates were reached in the sixth case
      scenario (session), whereas novices reached a plateau in the eighth session.
      Performance comparison of time to completion and errors showed significant
      improvement for both groups. Less time and fewer attempts were required by all
      trainees to complete a scenario while progressing through the curriculum. The
      overall number of IV cannulation attempts of novices was significantly higher
      than that of the intermediates throughout the course. CONCLUSIONS: Significant
      learning curves for novice and intermediate students were demonstrated after
      following the VR simulation-based curriculum. Competencies acquired during this
      educational course may provide an important advantage for training prior to
      actual clinical practice.

PMID- 21069897
TI  - Management of post-partum haemorrhage.
AB  - Management of post-partum haemorrhage (PPH) involves the treatment of uterine
      atony, evacuation of retained placenta or placental fragments, surgery due to
      uterine or birth canal trauma, balloon tamponade, effective volume replacement
      and transfusion therapy, and occasionally, selective arterial embolization. This
      article aims at introducing pregnancy- and haemorrhage-induced changes in
      coagulation and fibrinolysis and their relevant compensatory mechanisms, volume
      replacement therapy, optimal transfusion of blood products, and coagulation
      factor concentrates, and briefly cell salvage, management of uterine atony,
      surgical interventions, and selective arterial embolization. Special attention,
      respective management, and follow-up are required in women with bleeding
      disorders, such as von Willebrand disease, carriers of haemophilia A or B, and
      rare coagulation factor deficiencies. We also provide a proposal for practical
      instructions in the treatment of PPH.

PMID- 21069898
TI  - The effect of a simple checklist on frequent pre-induction deficiencies.
AB  - BACKGROUND: A substantial proportion of anaesthesia-related adverse events are
      preventable by identification and correction of errors in planning,
      communication, fatigue, stress, and equipment. The aim of this study was to
      develop and implement a pre-induction checklist in order to identify and solve
      problems before induction of anaesthesia. METHODS: The checklist was developed in
      a stepwise manner using a modified Delphi technique, literature search, expert's
      opinion, and a pilot version, and then implemented in a clinical environment
      during a 13-week study period. Each list was registered and analysed using
      statistical process control. The checklist was mandatory, but emergency cases
      were excluded. RESULTS: The checklist, containing 26 items, was used in 502 (61%)
      of a total of 829 inductions. Eighty-five checklists (17%) identified one or more
      missing items. The number of missing items decreased significantly throughout the
      study period. The most important missing items were lack of a second laryngoscope
      available, introducer not having been fitted to the endotracheal tube, the
      endotracheal tube cuff not having been tested, and no separate ventilation bag
      being available. It took a median of 88.5 s (range 52-118) to perform the
      checklist when no items were missing. The pre-induction time was the same before
      and after the checklist was introduced (25.1 vs. 24.3 min, P50.25). CONCLUSIONS:
      It is possible to develop, introduce, and use a pre-induction checklist even in a
      hectic and stressful clinical environment. The checklist identified and reduced a
      surprisingly large number of missing items required in a standard induction
      protocol.

PMID- 21069899
TI  - The effect of remifentanil on cough suppression after endoscopic sinus surgery: a
      randomized study.
AB  - BACKGROUND: Excessive coughing may increase the risk of complications after sinus
      surgery. We hypothesized that remifentanil would decrease the incidence and
      severity of coughing after endoscopic sinus surgery with propofol and
      remifentanil anaesthesia. METHODS: Ninety patients scheduled for endoscopic sinus
      surgery were randomly assigned into three groups. Propofol was stopped at the
      completion of the surgical procedure. The remifentanil infusion was adjusted to
      an effect-site concentration of 1.5, 2.0 or 2.5 ng/ml, 10 min before the
      anticipated end of surgery, in each of the three groups (RF1(.)5, RF2(.)0 and
      RF2(.)5) and continued until after extubation. The incidence and severity of
      coughing was evaluated on a scale from 0 to 3. RESULTS: The proportion of
      patients who did not cough was significantly higher in the RF2(.)0 (67.5%, 95%
      CI: 59.1- 75.9%) and RF2(.)5 (74.2%, 95% CI: 66.4-82.0%) groups than in the
      RF1(.)5 group (35.%, 95% CI: 26.5-43.5%) (P < 0.01). The incidence of grade 2 or
      3 coughing was significantly higher in the RF1(.)5 group (grade 2: 15.1%, grade
      3: 6.7%) than in the RF2(.)0 group (grade 2: 5.0%, grade 3: 0%) and the RF2(.)5
      group (grade 2: 4.2%, grade 3: 0%) (P < 0.05). There was no statistically
      significant difference in the time to extubation among the three groups.
      CONCLUSION: Maintaining anaesthesia with remifentanil to the end of the surgery,
      until after extubation, can suppress coughing without prolonging the recovery
      from anaesthesia. This effect is dose dependent and is more pronounced at higher
      concentrations of remifentanil (2.0 or 2.5 ng/ml).

PMID- 21069901
TI  - Accessory proteins in signal transduction: scaffold proteins and beyond.

PMID- 21069900
TI  - Transfusion has no effect on recurrence in hepatitis C after liver
      transplantation.
AB  - BACKGROUND: The literature suggests that blood product transfusions have a
      negative impact on the survival of liver transplant patients. We investigated the
      impact of intraoperative blood product usage on the survival of liver
      transplantation patients being transplanted for hepatitis C-related end-stage
      liver disease. In addition, we analyzed a potentially more sensitive metric,
      namely disease recurrence and fibrosis progression, obtained from follow-up liver
      biopsies. METHODS: We retrospectively studied 194 consecutive patients with
      hepatitis C virus (HCV) undergoing liver transplantation. To investigate the
      effect of red blood cell (RBC) or platelet transfusions on post-transplant HCV
      recurrence, hepatic biopsy data from 4 months and 1 year after transplantation
      were studied. In addition, survival data were analyzed. RESULTS: There was no
      effect of intraoperative RBC or platelet transfusion on either 1- or 5-year
      patient survival following liver transplantation. There was no difference in HCV
      disease recurrence or progression of hepatic fibrosis at 4 months or 1 year
      attributable either to RBC or to platelet transfusion. CONCLUSION: This study was
      not able to confirm an effect on the survival of HCV-infected liver transplant
      patients related to intraoperative transfusion of RBCs or platelets. In addition,
      these transfusions had no effect on HCV recurrence or fibrosis progression. This
      is not to condone a liberal transfusion practice, but rather to reassure that
      when clinically indicated, transfusion does not have a significant impact on
      patient survival or disease recurrence in HCV-infected liver transplant patients.

PMID- 21069902
TI  - Latency to first seizure after temporal lobectomy predicts  long-term outcome.
AB  - PURPOSE: Temporal lobectomy is a well-established treatment for refractory
      temporal lobe epilepsy, yet many patients experience at least one seizure
      postoperatively. Little is known about the prognostic significance of the time
      from surgery to first seizure relapse in predicting long-term outcome. METHODS:
      In a retrospective analysis of patients who reported at least one complex partial
      seizure (CPS) or generalized tonic-clonic seizure (GTCS) after anterior temporal
      lobectomy (n = 268), we used a nominal response logistic model to predict the
      odds ratio (OR) of a seizure outcome based on length of the latency period from
      surgery to first postoperative seizure. A modified Engel outcome class scheme was
      used. We controlled for factors known to influence postoperative outcome,
      including history of tonic-clonic seizures, intelligence quotient (IQ),
      preoperative seizure frequency, magnetic resonance imaging (MRI) findings, and
      history of febrile convulsions. RESULTS: In the univariate analysis, the latency
      from surgery to the first postoperative disabling seizure was significantly
      associated with long-term outcome. Longer latency was associated with higher odds
      of being seizure-free or improved (modified Engel's classes 1, 2, and 3) relative
      to the unimproved state (class 4) (p < 0.001, 0.001 and 0.004, respectively).
      Conversely, a shorter latency increased the likelihood of achieving the worst
      prognosis (class 4) relative to class 1 (p < 0.001). Multivariate analysis
      yielded similar results. DISCUSSION: Latency to the first postoperative seizure
      predicts long-term outcome, with short latencies portending poor prognosis and
      long latencies portending a good prognosis. This information can be used for
      patient counseling and may influence decisions regarding reoperation.

PMID- 21069904
TI  - Artifacts posing as premature ventricular beats in an "event recorder" tracing.

PMID- 21069903
TI  - Computerized classification of proximal occlusion in the left anterior descending
      coronary artery.
AB  - Proximal occlusion within the left anterior descending (LAD) coronary artery in
      patients with acute myocardial infarction leads to higher mortality than does
      nonproximal occlusion. We evaluated an automated program to detect proximal LAD
      occlusion. All patients with suspected acute coronary syndrome (n = 7,710)
      presenting consecutively to the emergency department of a local hospital with a
      coronary angiogram-confirmed flow-limiting lesion and notation of occlusion site
      were included in the study (n = 711). Electrocardiograms (ECGs) that met ST
      segment elevation myocardial infarction (STEMI) criteria were included in the
      training set (n = 183). Paired angiographic location of proximal LAD and ECGs
      with ST elevation in the anterolateral region were used for the computer program
      development (n = 36). The test set was based on ECG criteria for anterolateral
      STEMI only without angiographic reports (n = 162). Tested against 2 expert
      cardiologists' agreed reading of proximal LAD occlusion, the algorithm has a
      sensitivity of 95% and a specificity of 82%. The algorithm is designed to have
      high sensitivity rather than high specificity for the purpose of not missing any
      proximal LAD in the STEMI population. Our preliminary evaluation suggests that
      the algorithm can detect proximal LAD occlusion as an additional interpretation
      to STEMI detection with similar accuracy as cardiologist readers.

PMID- 21069905
TI  - Brain activation patterns of versive, hypermotor, and bilateral  asymmetric tonic
      seizures.
AB  - PURPOSE: Patients who have seizure onset from different brain regions can produce
      seizures that appear clinically indistinguishable from one another. These
      clinically stereotypic manifestations reflect epileptic activation of specific
      networks. Several studies have shown that ictal perfusion single photon emission
      computed tomography (SPECT) can reveal propagated ictal activity. We hypothesize
      that the pattern of hyperperfusion may reflect neuronal networks that generated
      specific ictal symptomatology. METHODS: All patients were identified who were
      injected with (99m)Tc-hexamethyl-propylene-amine-oxime (HMPAO) during versive
      seizures (n = 5), bilateral asymmetric tonic seizures (BATS; n = 5), and
      hypermotor seizures (n = 7) in the presurgical epilepsy evaluation between 2001
      and 2005. The SPECT ictal-interictal difference image pairs of each subgroup were
      compared with image pairs of 14 controls using statistical parametric mapping
      (SPM 2) to identify regions of significant hyperperfusion. Hyperperfused regions
      with corrected cluster-level significance p < 0.05 were considered significant.
      RESULTS: We have identified a distinct ictal perfusion pattern in each subgroup.
      In versive seizure subgroup, prominent hyperperfusion was present in the frontal
      eye field opposite to the direction of head version. In addition, there was
      associated caudate and crossed cerebellar hyperperfusion. The BATS subgroup
      showed pronounced hyperperfusion supplementary sensorimotor area ipsilateral to
      the epileptogenic region, bilateral basal ganglia, and contralateral cerebellar
      hemisphere. The hypermotor seizure subgroup demonstrated two clusters of
      significant hyperperfusion: one involving bilateral frontomesial regions,
      cingulate gyri, and caudate nuclei, and another involving ipsilateral
      anteromesial temporal structures, frontoorbital region, insula, and basal
      ganglia. DISCUSSION: We have identified distinct hyperperfusion patterns for
      specific ictal symptomatology. Our findings provide further insight into
      understanding the anatomic basis of seizure semiology.

PMID- 21069906
TI  - A European perspective-comments on "Infantile spasms: a U.S. consensus report".

PMID- 21069907
TI  - Comment on "Infantile spasms: a U.S. consensus report".

PMID- 21069909
TI  - Glycogenformation by Rhodococcus species and the effect of inhibition of lipid
      biosynthesis on glycogen accumulation in Rhodococcus opacus PD630.
AB  - Members of the genus Rhodococcus were investigated for their ability to produce
      glycogen during cultivation on gluconate or glucose. Strains belonging to
      Rhodococcus ruber, Rhodococcus opacus, Rhodococcus fascians, Rhodococcus
      erythropolis and Rhodococcus equi were able to produce glycogen up to 0.2-5.6% of
      cellular dry weight (CDW). The glycogen content varied from 0.8% to 3.2% of CDW
      in cells of R. opacus PD630, which is a well-known oleaginous bacterium, during
      the exponential growth phase, when cultivated on diverse carbon sources. Maltose
      and pyruvate promoted glycogen accumulation by cells of strain PD630 to a greater
      extent than glucose, gluconate, lactose, sucrose or acetate. This strain was able
      to produce triacylglycerols, polyhydroxyalkanoates and glycogen as storage
      compounds during growth on gluconate, although triacylglycerols were always the
      main product under the conditions of this study. Cerulenin, an inhibitor of de
      novo fatty acid synthesis, inhibited the accumulation of triacylglycerols from
      gluconate and increased the content of polyhydroxyalkanoates (from 2.0% to 4.2%,
      CDW) and glycogen (from 0.1% to 3.0%, CDW). An increase of the
      polyhydroxyalkanoates and glycogen content was also observed in two mutants of R.
      opacus PD630, which produced reduced amounts of triacylglycerols during
      cultivation of cells on gluconate.

PMID- 21069908
TI  - Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis
      pigmentosa.
AB  - Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal
      dystrophies characterised ultimately by the loss of photoreceptor cells. We have
      recently identified a new gene(EYS) encoding an ortholog of Drosophila space
      maker (spam) as a commonly mutated gene in autosomal recessive RP. In the present
      study, we report the identification of 73 sequence variations in EYS, of which 28
      are novel. Of these, 42.9% (12/28) are very likely pathogenic, 17.9% (5/28)are
      possibly pathogenic, whereas 39.3% (11/28) are SNPs. In addition, we have
      detected 3 pathogenic changes previously reported in other populations. We are
      also presenting the characterisation of EYS homologues in different species, and
      a detailed analysis of the EYS domains, with the identification of an interesting
      novel feature: a putative coiled-coil domain.Majority of the mutations in the
      arRP patients have been found within the domain structures of EYS. The minimum
      observed prevalence of distinct EYS mutations in our group of patients is of
      15.9% (15/94), confirming a major involvement of EYS in the pathogenesis of arRP
      in the Spanish population. Along with the detection of three recurrent mutations
      in Caucasian population, our hypothesis of EYS being the first prevalent gene in
      arRP has been reinforced in the present study.

PMID- 21069910
TI  - Resolving the native conformation of Escherichia coli OmpA.
AB  - The native conformation of the 325-residue outer membrane protein A (OmpA) of
      Escherichia coli has been a matter of contention. A narrow-pore, two-domain
      structure has vied with a large-pore, single-domain structure. Our recent studies
      show that Ser163 and Ser167 of the N-terminal domain (1-170) are modified in the
      cytoplasm by covalent attachment of oligo-(R)-3-hydroxybutyrates (cOHBs), and
      further show that these modifications are essential for the N-terminal domain to
      be incorporated into planar lipid bilayers as narrow pores (~ 80 pS, 1 m KCl, 22 
      degrees C). Here, we examined the potential effect(s) of periplasmic
      modifications on pore structure by comparing OmpA isolated from outer membranes
      (M-OmpA) with OmpA isolated from cytoplasmic inclusion bodies (I-OmpA). Chemical
      and Western blot analysis and 1H-NMR showed that segment 264-325 in M-OmpA, but
      not in I-OmpA, is modified by cOHBs. Moreover, a disulfide bond is formed between
      Cys290 and Cys302 by the periplasmic enzyme DsbA. Planar lipid bilayer studies
      indicated that narrow pores formed by M-OmpA undergo a temperature-induced
      transition into stable large pores (~ 450 pS, 1 M KCl, 22  degrees C) [energy of
      activation (Ea) = 33.2 kcal.mol(-1)], but this transition does not occur with I
      OmpA or with M-OmpA that has been exposed to disulfide bond-reducing agents. The
      results suggest that the narrow pore is a folding intermediate, and demonstrate
      the decisive roles of cOHB-modification, disulfide bond formation and temperature
      in folding OmpA into its native large-pore configuration.

PMID- 21069912
TI  - Education and imaging: Gastrointestinal: gastric anisakiasis presenting as a
      submucosal tumour diagnosed by endoscopic submucosal dissection.

PMID- 21069911
TI  - Clostridium difficile in vegetables, Canada.
AB  - BACKGROUND: Clostridium difficile is an important gastrointestinal pathogen of
      humans and animals. It has been isolated from various foods, including meat and
      ready-to-eat salads, and concern has been expressed regarding food as a possible
      source of human C. difficile infection (CDI). AIMS: We sought to isolate C.
      difficile from a variety of vegetables obtained from local grocery stores and to
      characterize these isolates. MATERIALS AND METHODS: Vegetables were purchased
      from 11 different grocery stores in Guelph, Ontario, Canada between May and
      August 2009. Enrichment culture was performed and isolates were characterized by
      ribotyping, PFGE, toxinotyping and PCR detection of toxin genes. RESULTS:
      Clostridium difficile was isolated from 4.5% (5/111) of retail vegetables. Two
      different ribotypes and two different toxinotypes were identified. Three isolates
      were ribotype 078/NAP 7/toxinotype V, possessing all three toxin genes. The other
      two isolates shared a ribotype with a toxigenic strain previously found in humans
      with CDI in this region. DISCUSSION: Contamination of vegetables was found at
      relatively low levels, however, all isolates were toxigenic and belonging to
      ribotypes previously associated with CDI. CONCLUSIONS: Contamination of
      vegetables with CDI-associated isolates can occur and although the implications
      for food safety practices remain elusive, the presence of toxigenic isolates
      suggests vegetables could be a source of C. difficile in humans.

PMID- 21069913
TI  - Education and imaging: Gastrointestinal: Bochdalek's hernia associated with
      gastric volvulus.

PMID- 21069914
TI  - What are the important drug use errors in dialysis patients? Pharmacokinetic and
      pharmacodynamic principles.

PMID- 21069915
TI  - Educational and imaging: Hepatobiliary and pancreatic: tuberculous liver abscess.

PMID- 21069916
TI  - Central nervous system medications.

PMID- 21069917
TI  - Antimicrobial agents.

PMID- 21069918
TI  - A successful pregnancy in a dialysis patient with renal cortical necrosis.

PMID- 21069919
TI  - Agents for the treatment of diabetes mellitus.

PMID- 21069920
TI  - Efficacy of mizoribine for steroid-resistant membranoproliferative
      glomerulonephritis type III.

PMID- 21069921
TI  - Cardiovascular agents.

PMID- 21069922
TI  - Non-compaction cardiomyopathy and polycystic kidney disease.

PMID- 21069923
TI  - Clinical relevance of impaired nonrenal drug clearance in ESRD.

PMID- 21069924
TI  - Confusion about the appropriate use of erythropoiesis-stimulating agents in
      patients undergoing maintenance dialysis.
AB  - The introduction of recombinant erythropoietin for clinical use in dialysis
      patients in 1989 was considered a major milestone for the long-term treatment of
      these vulnerable patients. It was assumed that increasing hemoglobin
      concentrations would not only improve patient-reported outcomes, as shown in
      early trials, but also reduce morbidity and mortality. Evidence that has
      accumulated over the ensuing two decades has repeatedly contradicted this
      assumption. The presence of powerful stake holders, strong competing incentives,
      strong prior beliefs, and scarce and confusing evidence have maintained
      uncertainty about the appropriate treatment of patients with chronic kidney
      disease who are anemic, including those requiring dialysis. This commentary
      recalls the decades-long scientific and regulatory journey and attempts to make
      the case for the urgent need for potentially paradigm-shifting evidence
      generation to identify the therapeutic sweet spot that would maximize net
      benefits of treatment with erythropoiesis-stimulating agents in patients
      undergoing dialysis.

PMID- 21069925
TI  - Confusion on the complexity of calcium balance.
AB  - Calcium balance is an overall assessment of the net calcium taken in minus the
      net calcium taken out. It can only be assessed when patients are in steady state
      and requires complicated isotope methods that can simultaneously assess
      intestinal absorption and endogenous secretion, urinary and stool excretion, bone
      calcium uptake and removal, and dialysate calcium removal. By virtue of the need
      for steady state, formal balance studies cannot be accurately carried out in
      patients on dialysis. However, many of the components of calcium balance have
      been assessed. Importantly, because 99% of calcium is in bone, studies must
      accurately assess both the rapidly exchangeable calcium from the bone surface and
      the net bone calcium balance that results from the difference in bone formation
      minus resorption. While it is tempting to adjust the dialysate calcium
      concentration to correct the net positive calcium balance that is likely present
      in patients who receive calcium-based phosphate binders, the reality is that the
      highly variable, yet important, role of bone cannot be easily assessed at the
      bedside. Thus, it is best to prevent the calcium overload in the first place by
      avoiding high-dose calcium-based phosphate binders and optimizing bone
      remodeling.

PMID- 21069926
TI  - Pancreas: NGAL is a potential early diagnostic and prognostic biomarker of severe
      acute pancreatitis.

PMID- 21069927
TI  - Ulcerative colitis: Bacteria penetrate the inner mucus layer of the colon.

PMID- 21069928
TI  - Pediatrics: EGID and feeding dysfunction.

PMID- 21069929
TI  - Cancer: A limited role for dual EGFR and ErbB2 inhibition in cholangiocarcinoma?

PMID- 21069930
TI  - IBD: Prostaglandin E2 inhibits fibroblast migration in intestinal wound healing.

PMID- 21069931
TI  - Transplantation: Anonymous living liver donors--outcomes and motivations.

PMID- 21069932
TI  - Biomarkers: FAK autophosphorylation independently predicts recurrence of gastric
      cancer.

PMID- 21069933
TI  - The definition of the venous ulcer.

PMID- 21069934
TI  - Management of primary venous disorders in C6 patients.

PMID- 21069935
TI  - Hydrogen sulfide as a signaling molecule in the enteric nervous system.
AB  - Hydrogen sulfide (H2S) is produced by sulfate-reducing bacteria present in the
      colon. Recently, it has been demonstrated that mammals have enzymatic pathways to
      produce H2S. As H2S was added to the list of gaseous signaling molecules, the
      number of papers related to H2S biology has increased exponentially. However, the
      physiological role of H2S in the gastrointestinal tract is still unknown.
      Endogenous production in different cell types indicates that H2S might
      participate in various functions such as pain, motility and secretion.
      Nevertheless, experimental protocols to demonstrate a physiological role for H2S
      are not easy to perform due to the lack of specific antagonists. Genetically
      modified animals lacking a specific route of H2S synthesis are useful biological
      tools although whether they alter gastrointestinal function are still unknown. In
      this issue of Neurogastroenterology and Motility, Krueger et al. examine the role
      of H2S in secretion and in afferent neuronal activation using sodium hydrosulfide
      as a source of H2S. Interestingly, sodium hydrosulfide causes secretion and
      increased spike activity in afferent neurons. The mechanism partly involves
      transient receptor potential vanilloid type I located on afferent neurons,
      causing local release of substance P, which in turn activates cholinergic
      secretomotor neurons. These novel observations extend our understanding of the
      function of H2S in the gastrointestinal tract.

PMID- 21069936
TI  - Erythropoietin enhances endogenous haem oxygenase-1 and represses immune
      responses to ameliorate experimental autoimmune encephalomyelitis.
AB  - Both erythropoietin (EPO) and haem oxygenase-1 (HO-1), an anti-oxidative stress
      protein, have proven protective roles in experimental autoimmune
      encephalomyelitis (EAE), a reliable animal model of multiple sclerosis. In this
      study, EPO delivered intraperitoneally could reduce disease severity in myelin
      oligodendrocyte glycoprotein (MOG)-EAE mice. To assess the effect of EPO on
      endogenous HO-1 in EAE, we investigated expression of HO-1 mRNA by real-time
      polymerase chain reaction (RT-PCR), protein expression centrally and peripherally
      by Western blot and immunohistochemistry and mean fluorescence intensity of
      splenic HO-1 by flow cytometry. A significantly higher expression of HO-1 in both
      the central nervous system (CNS) and spleen was shown in EPO-treated MOG-EAE mice
      than in controls.We further examined the immunomodulatory effect of EPO in EAE,
      and via RT-PCR demonstrated significantly lower expression of interferon-gamma,
      interleukin (IL)-23, IL-6 and IL-17 mRNA, and significantly higher expression of
      IL-4 and IL-10 mRNA in CNS of EPO-treated MOG-EAE mice than in controls. Using
      flow cytometry, we also observed a significantly decreased ratio of both T helper
      type 1 (Th1) and Th17 lymphocyte subsets isolated from CNS and a significantly
      increased ratio of splenic regulatory CD4 T cells in EPO-treated MOG-EAE mice. In
      addition, we demonstrated that MOG-specific T cell proliferation was lower in the
      EPO-treated group than in controls and showed amelioration of EAE by adoptive
      transfer of splenocytes from EPO-treated MOG-EAE mice. Together, our data show
      that in EAE, EPO induction of endogenous HO-1 and modulation of adaptive immunity
      both centrally and peripherally may involve the repression of inflammatory
      responses.

PMID- 21069938
TI  - Fifty percent reduction in venous ulcer prevalence is achievable - Swedish
      experience.

PMID- 21069939
TI  - Decreasing venous ulcers by 50% in 10 years: Five critical issues in the
      diagnosis and investigation of venous disease.

PMID- 21069940
TI  - Natural history and progression of primary chronic venous disorder.

PMID- 21069937
TI  - Relationship between target antigens and major histocompatibility complex (MHC)
      class II genes in producing two pathogenic antibodies simultaneously.
AB  - In this report,we present 15 patients with histological and immunopathologically
      proven pemphigus vulgaris (PV). After a mean of 80 months since the onset of
      disease, when evaluated serologically, they had antibodies typical of PV and
      pemphigoid (Pg). Similarly, 18 patients with bullous pemphigoid (BP) and mucous
      membrane pemphigoid (MMP) were diagnosed on the basis of histology and
      immunopathology.After a mean of 60 months since the onset of disease, when their
      sera were evaluated they were found to have Pg and PV autoantibodies. In both
      groups of patients the diseases were characterized by a chronic course, which
      included several relapses and recurrences and were non-responsive to conventional
      therapy. The major histocompatibility complex class II (MHC II) genes were
      studied in both groups of patients and phenotypes associated typically with them
      were observed. Hence, in 33 patients, two different pathogenic autoantibodies
      were detected simultaneously. The authors provide a computer model to show that
      each MHC II gene has relevant epitopes that recognize the antigens associated
      with both diseases. Using the databases in these computer models, the authors
      present the hypothesis that these two autoantibodies are produced simultaneously
      due to the phenomena of epitope spreading.

PMID- 21069942
TI  - [Translational research of molecular targeting drug for liver cancer].

PMID- 21069943
TI  - Searching for biological markers of molecular targeting treatment of liver
      cancer.

PMID- 21069941
TI  - Summary of evidence of effectiveness of primary chronic venous disease treatment.

PMID- 21069944
TI  - Efficacy of sorafenib, molecular targeting drug, for advanced hepatocellular
      carcinoma.

PMID- 21069945
TI  - [Placebo effect].

PMID- 21069946
TI  - [Strategies in research and development of anti-cancer drugs].

PMID- 21069947
TI  - [On special issue, "surgical therapy of recurrent or secondary lung cancer"].

PMID- 21069948
TI  - Lysis of aminobisphosphonate-sensitized MCF-7 breast tumor cells by
      Vgamma9Vdelta2 T cells.
AB  - Aminobisphosphonates are drugs administered for the treatment of bone resorption.
      They can indirectly activate peripheral gammadelta T cells and render tumor cells
      susceptible to lysis by Vgamma9Vdelta2 T cells. We have investigated the
      molecules involved in conjugate formation and killing of aminobisphosphonate
      treated MCF-7 breast tumor cells by Vgamma9Vdelta2 T cells. Lysis of
      aminobisphosphonate (Pamidronate and Zoledronate)-treated MCF-7 tumor cells by
      Vgamma9Vdelta2 T cells was assessed by chromium release assays and time-lapse
      video microscopy. MCF-7 breast cancer cells were chosen as aminobisphosphonates
      are employed to alleviate bone resorption in this malignancy. Cell cycle profile
      and expression of MICA, ICAM-I and FasL on aminobisphosphonate-sensitized MCF-7
      breast tumor cells was confirmed by flow cytometry. Involvement of gammadelta TCR
      and NKG2D in mediating cytotoxicity of aminobisphosphonate-treated MCF-7 breast
      tumor cells by Vgamma9Vdelta2 T cells was assessed using blocking antibodies in
      chromium release assays. MCF-7 tumor cells pretreated with Pamidronate and
      Zoledronate were efficiently lysed by Vgamma9Vdelta2 T cells. Pamidronate and
      Zoledronate treatment of MCF-7 cells induced S phase arrest and did not alter
      expression of MICA, ICAM-I and FasL. Blocking gammadelta TCR and NKG2D on
      Vgamma9Vdelta2 T cells inhibited lysis of Pamidronate and Zoledronate-treated MCF
      7 cells. Inhibiting the perforin-granzyme pathway in Vgamma9Vdelta2 T cells using
      concanamycin A reduced their ability to lyse aminobisphosphonate-treated MCF-7
      cells. Vgamma9Vdelta2 T cells form strong conjugates with aminobisphosphonate
      treated MCF-7 breast tumor cells. gammadelta TCR, NKG2D and perforin-granzyme
      pathway are involved in the lysis of MCF-7 breast tumor cells treated with
      aminobisphosphonates by Vgamma9Vdelta2 T cells.

PMID- 21069949
TI  - Predicting residential air exchange rates from questionnaires and meteorology:
      model evaluation in central North Carolina.
AB  - A critical aspect of air pollution exposure models is the estimation of the air
      exchange rate (AER) of individual homes, where people spend most of their time.
      The AER, which is the airflow into and out of a building, is a primary mechanism
      for entry of outdoor air pollutants and removal of indoor source emissions. The
      mechanistic Lawrence Berkeley Laboratory (LBL) AER model was linked to a leakage
      area model to predict AER from questionnaires and meteorology. The LBL model was
      also extended to include natural ventilation (LBLX). Using literature-reported
      parameter values, AER predictions from LBL and LBLX models were compared to data
      from 642 daily AER measurements across 31 detached homes in central North
      Carolina, with corresponding questionnaires and meteorological observations. Data
      was collected on seven consecutive days during each of four consecutive seasons.
      For the individual model-predicted and measured AER, the median absolute
      difference was 43% (0.17 h(-1)) and 40% (0.17 h(-1)) for the LBL and LBLX models,
      respectively. Additionally, a literature-reported empirical scale factor (SF) AER
      model was evaluated, which showed a median absolute difference of 50% (0.25 h(
      1)). The capability of the LBL, LBLX, and SF models could help reduce the AER
      uncertainty in air pollution exposure models used to develop exposure metrics for
      health studies.

PMID- 21069950
TI  - Non-uraninite products of microbial U(VI) reduction.
AB  - A promising remediation approach to mitigate subsurface uranium contamination is
      the stimulation of indigenous bacteria to reduce mobile U(VI) to sparingly
      soluble U(IV). The product of microbial uranium reduction is often reported as
      the mineral uraninite. Here, we show that the end products of uranium reduction
      by several environmentally relevant bacteria (Gram-positive and Gram-negative)
      and their spores include a variety of U(IV) species other than uraninite. U(IV)
      products were prepared in chemically variable media and characterized using
      transmission electron microscopy (TEM) and X-ray absorption spectroscopy (XAS) to
      elucidate the factors favoring/inhibiting uraninite formation and to constrain
      molecular structure/composition of the non-uraninite reduction products.
      Molecular complexes of U(IV) were found to be bound to biomass, most likely
      through P-containing ligands. Minor U(IV)-orthophosphates such as ningyoite
      [CaU(PO(4))(2)], U(2)O(PO(4))(2), and U(2)(PO(4))(P(3)O(10)) were observed in
      addition to uraninite. Although factors controlling the predominance of these
      species are complex, the presence of various solutes was found to generally
      inhibit uraninite formation. These results suggest a new paradigm for U(IV) in
      the subsurface, i.e., that non-uraninite U(IV) products may be found more
      commonly than anticipated. These findings are relevant for bioremediation
      strategies and underscore the need for characterizing the stability of non
      uraninite U(IV) species in natural settings.

PMID- 21069951
TI  - Remote identification and quantification of industrial smokestack effluents via
      imaging Fourier-transform spectroscopy.
AB  - Industrial smokestack plume emissions were remotely measured with a midwave
      infrared (1800-3000 cm(-1)) imaging Fourier-transform spectrometer operating at
      moderate spatial (128 * 64 with 19.4 * 19.4 cm(2) per pixel) and high spectral
      (0.25 cm(-1)) resolution over a 20 min period. Strong emissions from CO(2),
      H(2)O, SO(2), NO, HCl, and CO were observed. A single-layer plume radiative
      transfer model was used to estimate temperature T and effluent column densities
      q(i) for each pixel's spectrum immediately above the smokestack exit. Across the
      stack, temperature was uniform with T = 396.3 +/- 1.3 K (mean +/- stdev), and
      each q(i) varied in accordance with the plume path length defined by its
      cylindrical geometry. Estimated CO(2) and SO(2) volume fractions of 8.6 +/- 0.4%
      and 380 +/- 23 ppm(v), respectively, compared favorably with in situ measurements
      of 9.40 +/- 0.03% and 383 +/- 2 ppm(v). Total in situ NO(x) concentration (NO +
      NO(2)) was reported at 120 +/- 1 ppm(v). While NO(2) was not spectrally detected,
      NO was remotely observed with a concentration of 104 +/- 7 ppm(v). Concentration
      estimates for the unmonitored species CO, HCl, and H(2)O were 14.4 +/- 0.3
      ppm(v), 88 +/- 1 ppm(v), and 4.7 +/- 0.1%, respectively.

PMID- 21069952
TI  - A novel approach for the simultaneous determination of iodide, iodate and organo
      iodide for 127I and 129I in environmental samples using gas chromatography-mass
      spectrometry.
AB  - In aquatic environments, iodine mainly exists as iodide, iodate, and organic
      iodine. The high mobility of iodine in aquatic systems has led to (129)I
      contamination problems at sites where nuclear fuel has been reprocessed, such as
      the F-area of Savannah River Site. In order to assess the distribution of (129)I
      and stable (127)I in environmental systems, a sensitive and rapid method was
      developed which enables determination of isotopic ratios of speciated iodine.
      Iodide concentrations were quantified using gas chromatography-mass spectrometry
      (GC-MS) after derivatization to 4-iodo-N,N-dimethylaniline. Iodate concentrations
      were quantified by measuring the difference of iodide concentrations in the
      solution before and after reduction by Na(2)S(2)O(5). Total iodine, including
      inorganic and organic iodine, was determined after conversion to iodate by
      combustion at 900  degrees C. Organo-iodine was calculated as the difference
      between the total iodine and total inorganic iodine (iodide and iodate). The
      detection limits of iodide-127 and iodate-127 were 0.34 nM and 1.11 nM,
      respectively, whereas the detection limits for both iodide-129 and iodate-129 was
      0.08 nM (i.e., 2pCi (129)I/L). This method was successfully applied to water
      samples from the contaminated Savannah River Site, South Carolina, and more
      pristine Galveston Bay, Texas.

PMID- 21069953
TI  - Characterization factors for thermal pollution in freshwater aquatic
      environments.
AB  - To date the impact of thermal emissions has not been addressed in life cycle
      assessment despite the narrow thermal tolerance of most aquatic species. A method
      to derive characterization factors for the impact of cooling water discharges on
      aquatic ecosystems was developed which uses space and time explicit integration
      of fate and effects of water temperature changes. The fate factor is calculated
      with a 1-dimensional steady-state model and reflects the residence time of heat
      emissions in the river. The effect factor specifies the loss of species diversity
      per unit of temperature increase and is based on a species sensitivity
      distribution of temperature tolerance intervals for various aquatic species. As
      an example, time explicit characterization factors were calculated for the
      cooling water discharge of a nuclear power plant in Switzerland, quantifying the
      impact on aquatic ecosystems of the rivers Aare and Rhine. The relative
      importance of the impact of these cooling water discharges was compared with
      other impacts in life cycle assessment. We found that thermal emissions are
      relevant for aquatic ecosystems compared to other stressors, such as chemicals
      and nutrients. For the case of nuclear electricity investigated, thermal
      emissions contribute between 3% and over 90% to Ecosystem Quality damage.

PMID- 21069954
TI  - Measurement of dissolved organic matter fluorescence in aquatic environments: an
      interlaboratory comparison.
AB  - The fluorescent properties of dissolved organic matter (DOM) are often studied in
      order to infer DOM characteristics in aquatic environments, including source,
      quantity, composition, and behavior. While a potentially powerful technique, a
      single widely implemented standard method for correcting and presenting
      fluorescence measurements is lacking, leading to difficulties when comparing data
      collected by different research groups. This paper reports on a large-scale
      interlaboratory comparison in which natural samples and well-characterized
      fluorophores were analyzed in 20 laboratories in the U.S., Europe, and Australia.
      Shortcomings were evident in several areas, including data quality-assurance, the
      accuracy of spectral correction factors used to correct EEMs, and the treatment
      of optically dense samples. Data corrected by participants according to
      individual laboratory procedures were more variable than when corrected under a
      standard protocol. Wavelength dependency in measurement precision and accuracy
      were observed within and between instruments, even in corrected data. In an
      effort to reduce future occurrences of similar problems, algorithms for
      correcting and calibrating EEMs are described in detail, and MATLAB scripts for
      implementing the study's protocol are provided. Combined with the recent
      expansion of spectral fluorescence standards, this approach will serve to
      increase the intercomparability of DOM fluorescence studies.

PMID- 21069955
TI  - Electrospray ionization mass spectrometry characterization of interactions of
      newly identified water disinfection byproducts halobenzoquinones with
      oligodeoxynucleotides.
AB  - Four halobenzoquinones, 2,6-dibromo-1,4-benzoquinone, 2,6-dichloro-1,4
      benzoquinone, 2,6-dichloro-3-methyl-1,4-benzoquinone, and 2,3,6-trichloro-1,4
      benzoquinone, were recently identified as drinking water disinfection byproducts.
      Understanding their interactions with biomolecules could provide useful insights
      into their potential toxic effects. We report here electrospray ionization mass
      spectrometry characterization of the interactions between these new
      halobenzoquinone disinfection byproducts and oligodeoxynucleotides. The study
      demonstrates that 2,6-dibromo-1,4-benzoquinone exhibits much stronger binding to
      single- and double-stranded oligodeoxynucleotides than chlorobenzoquinones. The
      binding affinity of 2,6-dibromo-1,4-benzoquinone to oligodeoxynucleotides is
      similar to that of ethidium bromide, a well-known intercalator and carcinogen.
      Tandem mass spectrometry characterization confirms the formation of 1:1 and 2:1
      complexes of 2,6-dibromo-1,4-benzoquinone binding to oligodeoxynucleotides.
      Collision-induced dissociation analysis of these adducts demonstrates neutral
      loss and charge separation, suggesting that 2,6-dibromo-1,4-benzoquinone binds to
      oligodeoxynucleotides through partial intercalation and H-bonding modes. The
      three chlorobezoquinones also form 1:1 adducts with the oligodeoxynucleotides,
      but their binding to the oligodeoxynucleotides was much weaker compared to that
      of 2,6-dibromo-1,4-benzoquinone. The relative binding affinity of the studied
      disinfection byproducts to oligodeoxynucleotides is in the order of 2,6-dibromo
      1,4-benzoquinone?2,6-dichloro-1,4-benzoquinone > 2,6-dichloro-3-methyl-1,4
      benzoquinone ~ 2,3,6-trichloro-1,4-benzoquinone, indicating potential structural
      effects on the interactions of halobenzoquinones with oligodeoxynucleotides.

PMID- 21069957
TI  - Jackknife-based selection of Gram-Schmidt orthogonalized descriptors in QSAR.
AB  - This study is an implementation of a robust jackknife-based descriptor selection
      procedure assisted with Gram-Schmidt orthogonalization. Selwood data including 31
      molecules and 53 descriptors was considered in this study. Both multiple linear
      regression (MLR) and partial least squares (PLS) regression methods were applied
      during the jackknife procedures, and the desired results were obtained when using
      PLS regression on both autoscaled and orthogonalized data sets. Having used the
      Gram-Schmidt technique, descriptors were all orthogonalized, and their number was
      reduced to 30. A reproducible set of descriptors was obtained when PLS-jackknife
      was applied to the Gram-Schmidt orthogonalized data. The simple statistical t
      test was applied to determine the significance of the obtained regression
      coefficients from jackknife resampling.Increasing the sample size, descriptors,
      based on their information content, were introduced into the model one by one and
      were sorted. The number of validated descriptors was in proportion with the
      sample size in the jackknife. The PLS-jackknife parameters, such as sample size
      and number and number of latent variables in PLS, and the starting descriptor in
      Gram-Schmidt orthogonalization were investigated and optimized.Applying PLS
      jackknife to orthogonalized data in the optimized condition, five descriptors
      were validated with q2TOT2 ) 0.693 and R2 ) 0.811. Compared to the previous
      reports, the obtained results are satisfactory.

PMID- 21069958
TI  - LC-MS determination and pharmacokinetics of p-coumaric acid in rat plasma after
      oral administration of p-coumaric acid and freeze-dried red wine.
AB  - A sensitive and efficient liquid chromatography-mass spectrometry (LC-MS) method
      was developed and validated for the determination of p-coumaric acid (CA) in rat
      plasma. After addition of the internal standard (IS) hydrochlorothiazide and
      acidification with 2 M hydrochloric acid, plasma samples were extracted by ethyl
      acetate and separated on a Kromasil C18 column (200 mm * 4.6 mm, 5 MUm) using a
      mobile phase composed of methanol-0.50/00 acetic acid (60:40, v/v) within a
      runtime of 6.0 min. Analysis was performed in selected ion monitoring (SIM) mode
      with a negative electrospray ionization (ESI) interface. The target ions were m/z
      163.15 for CA and m/z 295.95 for IS. The linear range was 0.01-15 MUg.mL(-1), and
      the lower limit of quantification (LLOQ) was 0.01 MUg.mL(-1). The intraday and
      interday precision (RSD %) were lower than 10% and accuracy (RE%) ranged from
      97.1 to 103.2%. The validated method was successfully applied to the comparative
      pharmacokinetic study of CA in rat plasma after oral administration of CA and
      freeze-dried red wine, respectively. It was found that both AUC and T1/2 of CA in
      freeze-dried red wine were increased significantly (p < 0.05) compared with that
      in monomer. In addition, a double-peak profile could be observed from the
      concentration-time curve after oral administration of freeze-dried red wine. 

PMID- 21069960
TI  - Disclosure of the elusive C2v-C72 carbon cage.
AB  - The stability of all fullerenes (closed carbon cages composed of pentagons and
      hexagons) can be explained by a simple empirical rule that forbids direct
      pentagon pentagon junctions (the isolated pentagon rule). Among thousands of
      possible fullerene structures, only one was predicted to violate this rule,
      namely, C2v-symmetric (#11188)C72. In this work, we present the synthesis and
      isolation of this elusive fullerene cage for the first time. The C2v-C72 cage was
      captured by in situ chlorination to form C72Cl4, whose structure was
      unambiguously determined by single-crystal X-ray analysis. The chlorination
      pattern and resulting stability of C72Cl4 are discussed.

PMID- 21069959
TI  - Chemical defects in the highly fluorescent conjugated polymer dots.
AB  - We present strong evidence for the oxidation of conjugated polymers in the
      formation of conjugated polymer dots (CPdots) using Fourier transform infrared
      spectroscopy and X-ray photoelectron spectroscopy. Although recent studies show
      that folding of the polymer chain into a compact 3D structure is involved in the
      formation of these nanoparticles, the process by which these intrinsically
      hydrophobic nanoscale particles circumvent aggregation in water is still not well
      understood. Zeta potential results show that these dots have a negatively charged
      surface at neutral pH, with a zeta potential and surface charge density of
      approximately -40 mV and (1.39 - 1.70) * 10(-2) C/m(2), respectively. In
      addition, quantitative elemental analysis of CPdots indicates that oxygen
      composes 7-13% of these nanoparticles. The overall results support the presence
      of chemical defects in forming a hydrophilic surface of CPdots. As a consequence,
      the charged surface contributes to inhibiting the aggregation of CPdots in water,
      leading to colloidal stability.

PMID- 21069961
TI  - Conductivity of ruthenate nanosheets prepared via electrostatic self-assembly:
      characterization of isolated single nanosheet crystallite to mono- and multilayer
      electrodes.
AB  - Ultrathin films composed of ruthenate nanosheets (RuO(2)ns) were fabricated via
      electrostatic self-assembly of unilamellar RuO(2)ns crystallites derived by total
      exfoliation of an ion-exchangeable layered ruthenate. Ultrathin films with
      submonolayer to monolayer RuO(2)ns coverage and multilayered RuO(2)ns thin films
      were prepared by controlled electrostatic self-assembly and layer-by-layer
      deposition using a cationic copolymer as the counterion. Electrical properties of
      a single RuO(2)ns crystallite were successfully measured by means of scanning
      probe microscopy. The sheet resistance of an isolated single RuO(2)ns crystallite
      was 12 kOmega sq(-1). Self-assembled submonolayer films behaved as a continuous
      conducting film for coverage above 70%, which was discussed based on a two
      dimensional percolation model. Low sheet resistance was attained for multilayered
      films with values less than 1 kOmega sq(-1). Interestingly, the grain boundary
      resistance between nanosheets seems to contribute only slightly to the sheet
      resistance of self-assembled films.

PMID- 21069962
TI  - Synthesis and structure-activity relationships of aza- and diazabiphenyl
      analogues of the antitubercular drug (6S)-2-nitro-6-{[4
      (trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).
AB  - New heterocyclic analogues of the potent biphenyl class derived from
      antitubercular drug PA-824 were prepared, aiming to improve aqueous solubility
      but maintain high metabolic stability and efficacy. The strategy involved
      replacement of one or both phenyl groups by pyridine, pyridazine, pyrazine, or
      pyrimidine, in order to reduce lipophilicity. For para-linked biaryls,
      hydrophilicities (ClogP) correlated with measured solubilities, but highly
      soluble bipyridine analogues displayed weak antitubercular activities. A terminal
      pyridine or proximal heterocycle allowed retention of potency and provided
      solubility improvements, particularly at low pH, with examples from the latter
      classes displaying the better in vivo efficacies, high metabolic stabilities, and
      excellent pharmacokinetics. Five such compounds were >100-fold better than the
      parent drug in a mouse model of acute Mycobacterium tuberculosis infection, and
      two orally bioavailable pyridine analogues (3-4-fold more soluble than the parent
      at low pH) were superior to antitubercular drug OPC-67683 in a chronic infection
      model. 

PMID- 21069963
TI  - Effect of humidity on the interaction of dimethyl methylphosphonate (DMMP) vapor
      with SiO2 and Al2O3 surfaces, studied using infrared attenuated total reflection
      spectroscopy.
AB  - Infrared attenuated total reflection spectroscopy has been used to study the
      interaction of DMMP vapor with SiO(2), Al(2)O(3), and AlO(OH) vs relative
      humidity (RH) and DMMP partial pressure (P/P(0)). For SiO(2) the growth with
      increasing RH of ice-like and liquid-like layers is seen in agreement with
      previous work. H<->D exchange during exposure to H(2)O and D(2)O indicates that
      the ice-like layer is more resistant to exchange, consistent with stronger H
      bonding than in the liquid-like layer. Exposure of nominally dry SiO(2) to D(2)O
      indicates the existence of adsorbed H(2)O that does not exhibit an ice-like
      spectrum. The ice-like layer appears only at a finite RH. Exposure of SiO(2) to
      DMMP in the absence of intentionally added H(2)O shows the formation of a
      strongly bound molecular species followed by a liquid-like layer. The strong
      interaction involves SiO-H...O?P bonds to surface silanols and/or HO-H...O?P
      bonds to preadsorbed molecular H(2)O. At a finite RH the ice-like layer forms on
      SiO(2) even in the presence of DMMP up to P/P(0) = 0.30. DMMP does not appear to
      penetrate the ice-like layer under these conditions, and the tendency to form a
      such a layer drives the displacement of DMMP. Amorphous Al(2)O(3) and AlO(OH) do
      not exhibit an ice-like H(2)O layer. Both have a higher surface OH content than
      does SiO(2), which leads to higher coverages of H(2)O or DMMP at equivalent RH or
      P/P(0). At low P/P(0), for which adsorption is dominated by Al-OH...O?P bonding,
      a-Al(2)O(3) interacts with DMMP more strongly than does AlO(OH) as a result of
      the higher acidity of OH sites on the former. Up to RH = 0.30 and P/P(0) = 0.30,
      DMMP appears to remain bonded to the surface rather than being displaced by
      H(2)O. H(2)O appears to have little or no effect on the total amount of DMMP
      adsorbed on any of these surfaces, up to an RH of 0.30 and a P/P(0) of 0.30. The
      results have implications for the transport of DMMP and related molecules on
      oxide surfaces in the environment.

PMID- 21069964
TI  - Synthesis of 4-aryl- and 4-alkyl-2-silyl-1,3-butadienes and their Diels
      Alder/cross-coupling reactions.
AB  - An ene-yne cross methasis of silyl-substituted alkynes and alkenes has been
      developed as a route to 4-aryl- and 4-alkyl-2-silyl-substituted 1,3-dienes. The
      dienes prepared were used to affect highly diastereoselective Diels-Alder
      reactions and then the silicon-substituted Diels-Alder cycloadducts were used in
      Hiyama cross-coupling reactions. The cross-coupling reactions enable these
      silicon dienes to be used as synthons for a variety of other dienes one might
      prepare and need access to. Two of the silicon-substituted Diels-Alder
      cycloadducts and one of the Hiyama cross-coupling products were also
      characterized by X-ray crystallography.

PMID- 21069965
TI  - FT-ICR-MS characterization of intermediates in the biosynthesis of the alpha
      methylbutyrate side chain of lovastatin by the 277 kDa polyketide synthase LovF.
AB  - There are very few fungal polyketide synthases that have been characterized by
      mass spectrometry. In this paper we describe the in vitro reconstitution and FT
      ICR-MS verification of the full activity of an intact 277 kDa fungal polyketide
      synthase LovF of the lovastatin biosynthetic pathway. We report here both the
      verification of the reconstitution of fully functional holo-LovF by using (13)C
      labeled malonyl-CoA to form alpha-methylbutyrate functionality and also detection
      of five predicted intermediates covalently bound to the 4'-phosphopantetheine at
      the acyl carrier protein (ACP) active site utilizing the phosphopantetheine
      ejection assay and high-resolution mass spectrometry. Under in vitro conditions,
      the diketide acetoacetyl intermediate did not accumulate on the ACP active site
      of holo-LovF following incubation with malonyl-CoA substrate. We found that
      incubation of holo-LovF with acetoacetyl-CoA served as an effective means of
      loading the diketide intermediate onto the ACP active site of LovF. Our results
      demonstrate that subsequent alpha-methylation of the acetoacetyl intermediate
      stabilizes the intermediate onto the ACP active site and facilitates the
      formation and mass spectrometric detection of additional intermediates en route
      to the formation of alpha-methylbutyrate.

PMID- 21069966
TI  - Characterization of currently marketed heparin products: reversed-phase ion
      pairing liquid chromatography mass spectrometry of heparin digests.
AB  - Here we report results from the analyses by enzymatic digestion and reversed
      phase ion-pairing liquid chromatography mass spectrometry (RPIP-LC-MS) of active
      pharmaceutical ingredient (API) unfractionated heparins (UFHs) from six different
      manufacturers and one USP standard sample. We employed a reverse phase ion
      pairing chromatography method using a C(18) column and hexylamine as the ion
      pairing reagent with acetonitrile gradient elution to separate disaccharides
      generated from the digestion of the heparins by lyase I and III (E.C. 4.2.2.7 and
      4.2.2.8) before introduction into an ion-trap mass spectrometer by an
      electrospray ionization (ESI) interface. Extracted ion chromatograms (EICs) were
      used to determine the relative abundance of the disaccharides by mass
      spectrometry. Eight disaccharides were observed and a similar composition profile
      was observed from digests of 20 UFH samples. The compositional profile determined
      from these experiments provides a measure of the norm and range of variation in
      "good" heparin to which future preparations can be compared. Furthermore, the
      profile obtained in the RPIP-LC-MS assay is sensitive to the presence of the
      contaminant, oversulfated chondroitin sulfate A (OSCS), in heparin.

PMID- 21069967
TI  - Fluorescent polymer sensor array for detection and discrimination of explosives
      in water.
AB  - A fluorescent polymer sensor array (FPSA) was made from commercially available
      fluorescent polymers coated onto glass beads and was tested to assess the ability
      of the array to discriminate between different analytes in aqueous solution. The
      array was challenged with exposures to 17 different analytes, including the
      explosives trinitrotoluene (TNT), tetryl, and RDX, various explosive-related
      compounds (ERCs), and nonexplosive electron-withdrawing compounds (EWCs). The
      array exhibited a natural selectivity toward EWCs, while the non-electron
      withdrawing explosive 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) produced no
      response. Response signatures were visualized by principal component analysis
      (PCA), and classified by linear discriminant analysis (LDA). RDX produced the
      same response signature as the sampled blanks and was classified accordingly. The
      array exhibited excellent discrimination toward all other compounds, with the
      exception of the isomers of nitrotoluene and aminodinitrotoluene. Of particular
      note was the ability of the array to discriminate between the three isomers of
      dinitrobenzene. The natural selectivity of the FPSA toward EWCs, plus the ability
      of the FPSA to discriminate between different EWCs, could be used to design a
      sensor with a low false alarm rate and an excellent ability to discriminate
      between explosives and explosive-related compounds.

PMID- 21069968
TI  - Surface plasmon resonance for rapid screening of uranyl affine proteins.
AB  - A sensitive immunoassay based on SPR analysis was developed to measure uranyl
      cation (UO(2)(2+)) affinity for any protein in a free state under physiological
      conditions. The technique involves immobilization of a specific monoclonal
      antibody (mAb) raised against UO(2)(2+) and 1,10-phenanthroline-2,9-dicarboxylic
      acid (DCP) used as a probe of UO(2)(2+) captured by the mAb. Calibration curves
      were established for accurate determination of UO(2)(2+) concentrations with a
      detection limit of 7 nM. The remaining free UO(2)(2+) could be accurately
      quantified from the different protein-metal equilibrium and a dose-response curve
      established for K(D) determination. This generic method was applied not only to
      proteins such as transferrin and albumin but also to small phosphonated ligands.
      Its robustness allows the fast UO(2)(2+) K(D) determination of any kind of
      macromolecules and small ligands using very few amount of compounds, thus opening
      new prospects in the field of uranium toxicity.

PMID- 21069969
TI  - Highly sensitive, colorimetric detection of mercury(II) in aqueous media by
      quaternary ammonium group-capped gold nanoparticles at room temperature.
AB  - We provide a highly sensitive and selective assay to detect Hg(2+) in aqueous
      solutions using gold nanoparticles modified with quaternary ammonium group
      terminated thiols at room temperature. The mechanism is the abstraction of thiols
      by Hg(2+) that led to the aggregation of nanoparticles. With the assistance of
      solar light irradiation, the detection limit can be as low as 30 nM, which
      satisfies the guideline concentration of Hg(2+) in drinking water set by the WHO.
      In addition, the dynamic range of detection is wide (3 * 10(-8)-1 * 10(-2) M).
      This range, to our best knowledge, is the widest one that has been reported so
      far in gold nanoparticle (AuNP)-based assays for Hg(2+).

PMID- 21069970
TI  - Dynamics and structural changes induced by ATP binding in SAV1866, a bacterial
      ABC exporter.
AB  - Multidrug transporters of the ATP-binding cassette family export a wide variety
      of compounds across membranes in both prokaryotes and eukaryotes, using ATP
      hydrolysis as energy source. Several of these membrane proteins are of clinical
      importance. Although biochemical and structural studies have provided insights
      into the mechanism underlying substrate transport, many key questions subsist
      regarding the molecular and structural nature of this mechanism. In particular,
      the detailed conformational changes occurring during the catalytic cycle are
      still elusive. We explored the conformational changes occurring upon ATP/Mg(2+)
      binding using molecular dynamics simulations starting from the nucleotide-bound
      structure of SAV1866 embedded in an explicit lipid bilayer. The removal of
      nucleotide revealed a major rearrangement in the outer membrane leaflet portion
      of the transmembrane domain (TMD) resulting in the closure of the central cavity
      at the extracellular side. This closure is similar to that observed in the
      crystal nucleotide-free structures. The interface of the nucleotide-binding
      domain dimer (NDB) is significantly more hydrated in the nucleotide-free
      trajectory though it is not disrupted. This finding suggests that the TMD closure
      could occur as a first step preceding the dissociation of the dimer. The
      transmission pathway of the signal triggered by the removal of ATP/Mg(2+) mainly
      involves the conserved Q-loop and X-loop as well as TM6.

PMID- 21069971
TI  - Atmospheric oxygen binding and hole doping in deformed graphene on a SiO2
      substrate.
AB  - Using micro-Raman spectroscopy and scanning tunneling microscopy, we study the
      relationship between structural distortion and electrical hole doping of graphene
      on a silicon dioxide substrate. The observed upshift of the Raman G band
      represents charge doping and not compressive strain. Two independent factors
      control the doping: (1) the degree of graphene coupling to the substrate and (2)
      exposure to oxygen and moisture. Thermal annealing induces a pronounced
      structural distortion due to close coupling to SiO2 and activates the ability of
      diatomic oxygen to accept charge from graphene. Gas flow experiments show that
      dry oxygen reversibly dopes graphene; doping becomes stronger and more
      irreversible in the presence of moisture and over long periods of time. We
      propose that oxygen molecular anions are stabilized by water solvation and
      electrostatic binding to the silicon dioxide surface. 

PMID- 21069973
TI  - Exciton annihilation and energy transfer in self-assembled peptide-porphyrin
      complexes depends on peptide secondary structure.
AB  - We used picosecond transient absorption and fluorescence lifetime spectroscopy to
      study singlet exciton annihilation and depolarization in self-assembled
      aggregates of meso-tetra(4-sulfonatophenyl)porphine (TPPS(4)) and a synthetic 22
      residue polypeptide. The polypeptide was designed and previously shown to bind
      three TPPS(4) monomers via electrostatic interactions between the sulfonate
      groups and cationic lysine residues. Additionally, the peptide induces formation
      of TPPS(4) J-aggregates in acidic solutions when the peptide secondary structure
      is disordered. In neutral solutions, the peptide adopts an alpha-helical
      secondary structure that can bind TPPS(4) with high affinity but J-aggregate
      formation is inhibited. Detailed analysis of excitation-power dependent transient
      absorption kinetics was used to obtain rate constants describing the energy
      transfer between TPPS(4) molecules in an aggregate under acidic and neutral
      conditions. Independently, such analysis was confirmed by picosecond fluorescence
      emission depolarization measurements. We find that energy transfer between
      TPPS(4) monomers in a peptide-TPPS(4) complex is more than 30 times faster in
      acidic aqueous solution than in neutral solutions (9 vs 279 ps). This result was
      attributed to a conformational change of the peptide backbone from disordered at
      low pH to alpha-helical at neutral pH and suggests a new approach to control
      intermolecular energy transfer with possible applications in fluorescent sensors
      or biomimetic light harvesting antennas.

PMID- 21069972
TI  - Site-selective electroless nickel plating on patterned thin films of
      macromolecular metal complexes.
AB  - We demonstrate a simple route to depositing nickel layer patterns using
      photocross-linked polymer thin films containing palladium catalysts, which can be
      used as adhesive interlayers for fabrication of nickel patterns on glass and
      plastic substrates. Electroless nickel patterns can be obtained in three steps:
      (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV
      irradiation, (ii) the formation of macromolecular metal complex with palladium,
      and (iii) the nickel metallization using electroless plating bath. Metallization
      is site-selective and allows for a high resolution. And the resulting nickel
      layered structure shows good adhesion with glass and plastic substrates. The
      direct patterning of metallic layers onto insulating substrates indicates a great
      potential for fabricating micro/nano devices.

PMID- 21069974
TI  - How does dielectric solvation affect the size of an ion?
AB  - The effect of solvation by a continuum dielectric on the size of an ion is
      examined using electronic structure calculations. Various measures correlated
      with size are considered, including the root-mean-square radius of the electronic
      charge density, the amount of solute charge penetrating outside the cavity, the
      electronic radial distribution function, the nucleus-electron potential energy,
      and the electron-electron potential energy. Calculations are made on several
      representative ionic solutes, and it is found that every measure indicates that
      the application of a dielectric makes the cations larger and the anions smaller.
      These counterintuitive trends are examined, and a plausible explanation is
      offered for the observed behavior.

PMID- 21069975
TI  - Ultrafast intramolecular charge transfer with N-(4-cyanophenyl)carbazole.
      Evidence for a LE precursor and dual LE + ICT fluorescence.
AB  - The photophysics of N-(4-cyanophenyl)carbazole (NP4CN) was investigated by using
      absorption and fluorescence spectra, picosecond fluorescence decays, and
      femtosecond transient absorption. In the nonpolar n-hexane as well as in the
      polar solvent acetonitrile (MeCN), a locally excited (LE) state is detected, as a
      precursor for the intramolecular charge transfer (ICT) state. A LE -> ICT
      reaction time tau(2) at 22  degrees C of 0.95 ps in ethyl cyanide (EtCN) and 0.32
      ps in MeCN is determined from the decay of the LE excited state absorption (ESA)
      maximum around 620 nm. In the ESA spectrum of NP4CN in n-hexane at a pump-probe
      delay time of 100 ps, an important contribution of the LE band remains alongside
      the ICT band, in contrast to what is observed in EtCN and MeCN. This shows that a
      LE ? ICT equilibrium is established in this solvent and the ICT reaction time of
      0.5 ps is equal to the reciprocal of the sum of the forward and backward ICT rate
      constants 1/(k(a) + k(d)). In the photostationary S(0) -> S(n) absorption
      spectrum of NP4CN in n-hexane and MeCN, an additional CT absorption band appears,
      absent in the sum of the spectra of its electron donor (D) and acceptor (A)
      subgroups carbazole and benzonitrile. This CT band is located at an energy of
      ~4000 cm(-1) lower than for N-phenylcarbazole (NPC), due to the larger electron
      affinity of the benzonitrile moiety of NP4CN than the phenyl subunit of NPC. The
      fluorescence spectrum of NP4CN in n-hexane at 25  degrees C mainly consists of a
      structured LE emission, with a small ICT admixture, indicating that a LE -> ICT
      reaction just starts to occur under these conditions. In di-n-pentyl ether (DPeE)
      and di-n-butyl ether (DBE), a LE emission is found upon cooling at the high
      energy edge of the ICT fluorescence band, caused by the onset of dielectric
      solvent relaxation. This is not the case in more polar solvents, such as diethyl
      ether (DEE) and MeCN, in which a structureless ICT emission band fully overlaps
      the strongly quenched LE fluorescence. For the series of D/A molecules NPC, N-(4
      fluorophenyl)carbazole (NP4F), N-[4-(trifluoromethyl)phenyl]carbazole (NP4CF),
      and NP4CN, with increasing electron affinity of their phenyl subgroup, an ICT
      emission in n-hexane 25  degrees C only is present for NP4CN, whereas in MeCN an
      ICT fluorescence is observed with NP4CF and NP4CN. The ICT fluorescence appears
      when for the energies E(ICT) of the ICT state and E(S(1)) of the lowest excited
      singlet state the condition E(ICT) <= E(S(1)) holds. E(ICT) is calculated from
      the difference E(D/D(+)) - E(A(-)/A) of the redox potentials of the D and A
      subgroups of the N-phenylcarbazoles. From solvatochromic measurements with NP4CN
      an ICT dipole moment MU(e)(ICT) = 19 D is obtained, somewhat larger than the
      literature values of 10-16 D, because of a different Onsager radius rho. The
      carbazole/phenyl twist angle theta = 45 degrees  of NP4CN in the S(0) ground
      state, determined from X-ray crystal analysis, has become smaller for its ICT
      state, in analogy with similar conclusions for related N-phenylcarbazoles and
      other D/A molecules in the literature.

PMID- 21069976
TI  - Electronic spectra of protonated benzaldehyde clusters with Ar and N2: effect of
      pipi* excitation on the intermolecular potential.
AB  - Electronic spectra of the S(1)<-S(0) transition of dimers of protonated
      benzaldehyde (BZH(+)) with Ar and N(2) are recorded by resonance-enhanced
      photodissociation in a tandem mass spectrometer. The S(1) origins observed are
      shifted to higher frequency upon complexation with Ar (DeltaS(1) = 300 cm(-1))
      and N(2) (DeltaS(1) = 628 cm(-1)). Ab initio calculations at the CC2/aug-cc-pVDZ
      level suggest an assignment to H-bonded dimers of L = Ar and N(2) binding to the
      cis isomer of O-protonated BZH(+), yielding values of DeltaS(1) = 242 and 588 cm(
      1) for cis-BZH(+)-L(H). Electronic pipi* excitation results in a substantial
      increase of the proton affinity of BZH(+), which in turn destabilizes the
      intermolecular H-bonds to the inert ligands by 35%. The drastic effects of
      electronic pipi* excitation on the geometric and electronic structure as well as
      the strength and anisotropy of the intermolecular potential (H-bonding and pi
      bonding) are investigated.

PMID- 21069977
TI  - Biradical character of linear pi-conjugated oligomer dications composed of
      thiophene, pyrrole, and methylthio end-capping units.
AB  - Combined DFT calculations and UV-vis-NIR, ESR, and SQUID measurements revealed
      that the ground-state electronic structure of a linear pi-conjugated oligomer
      dication composed of two pyrrole and six or seven thiophene rings and methylthio
      end-capping units is dominated by a singlet biradical character.

PMID- 21069978
TI  - Controlling liquid crystal alignment using photocleavable cyanobiphenyl self
      assembled monolayers.
AB  - We report on the development of novel cyano-biphenyl-based thiolate self
      assembled monolayers designed to promote homeotropic alignment of calamitic
      liquid crystals. The molecules developed contain an ortho-nitrobenzyl protected
      carboxylic acid group that on irradiation by soft UV (365 nm) is cleaved to yield
      carboxylic acid groups exposed at the surface that promote planar alignment.
      Using a combination of wetting, X-ray photoelectron spectroscopy, Fourier
      transform-infrared reflection absorption spectroscopy, and ellipsometry we show
      that high photolysis yields (>90%) can be achieved and that the patterned SAMs
      are suitable for the controlled alignment of calamitic liquid crystals. This
      study further shows that such photo-patterned SAMs can be used to control the
      formation of focal conic domains (FCDs) in the smectic-A phase in terms of
      positioning and size confinement on surfaces.

PMID- 21069979
TI  - Optical and excitonic properties of crystalline ZnS nanowires: toward efficient
      ultraviolet emission at room temperature.
AB  - A systematic investigation into the excitonic properties of wurtzite ZnS
      nanowires (NWs) is presented. Under optical excitation, the ZnS NWs exhibit
      strong ultraviolet (UV) emission. Optical transition from free exciton A, free
      exciton B, and shallow level emission are observed and analyzed through power
      dependent and temperature-dependent photoluminescence spectroscopy measurements
      performed from 10 to 300 K. The excitonic transition and coupling strength of
      exciton-longitudinal optical phonon were directly determined from the evolution
      of exciton peak energy and peak width broadening. Our studies indicate that free
      excitons in ZnS nanowires are very stable, suggesting a great promise for high
      efficiency light-emitting devices and lasers in the UV region. Finally, the
      carrier dynamics of the ZnS NWs were measured and analyzed for the first time by
      ultrafast spectroscopy. 

PMID- 21069980
TI  - High-efficiency single-molecule detection within trapped aqueous microdroplets.
AB  - Aqueous droplets were used as a tool to confine a molecular population and enable
      highly efficient detection at the single-molecule level. Picoliter-sized aqueous
      droplets were generated using classical multiphase microfluidics with an aqueous
      stream containing the analyte under investigation and an oil carrier phase. The
      droplets were then localized and isolated in specially designed trapping areas
      within the microfluidic channel to provide a static environment for detection of
      the encapsulated molecules. We show that by continuously flowing the carrier oil
      phase while holding the aqueous stationary, we can significantly improve on
      measuring repeat single-molecule events. Further, we find that the flowing oil
      stream induces a circulation within the trapped droplets which is proportional to
      the volumetric flow velocity. This circulation phenomenon allows a given molecule
      to be detected multiple times during an experiment and can therefore be used for
      performing time-dependent single-molecule analysis.

PMID- 21069981
TI  - Iterative synthesis of heterotelechelic oligo(phenylene-vinylene)s by olefin
      cross-metathesis.
AB  - A novel iterative synthesis of heterotelechelic oligo(phenylene-vinylene)s using
      olefin cross-metathesis is reported. The metathesis homologation proceeds in good
      yields and allows for further functionalization, including the facile formation
      of donor-acceptor complexes and repeating sequence copolymers.

PMID- 21069982
TI  - New chiral ferrocenyl P,S-ligands for highly diastereo-/enantioselective
      catalytic [3 + 2] cycloaddition of azomethine ylides with cyclic and acyclic
      enones.
AB  - A new family of chiral ferrocenyl P,S-ligands has been developed and successfully
      applied in a highly endo-selective catalytic asymmetric cycloaddition of
      azomethine ylides with various enones, including cyclic and acyclic alpha-enones.
      For cyclic alpha-enones, a [Cu(CH(3)CN)(4)]ClO(4)/(R(c),S(Fc))-2f complex
      catalyzed the cycloaddition to give the sole endo-cycloadducts in perfect
      enantioselectivities (normally 99% ee), while an AgOAc/(R(c),S(Fc))-2f catalytic
      system exhibited good endo/exo selectivities (endo/exo = 91/9 to 96/4) and high
      enantiocontrol (up to 98% ee) for acyclic alpha-enones.

PMID- 21069983
TI  - Cationic rhodium(I) complex-catalyzed cotrimerization of propargyl esters and
      arylacetylenes leading to substituted dihydropentalenes.
AB  - It has been established that a cationic rhodium(I)/cod complex catalyzes the
      cotrimerization of propargyl esters and arylacetylenes, leading to substituted
      dihydropentalenes, in the presence of excess cod through elimination of
      carboxylic acids.

PMID- 21069984
TI  - Chiral diene as the ligand for the synthesis of axially chiral compounds via
      palladium-catalyzed Suzuki-Miyaura coupling reaction.
AB  - The first palladium-diene-catalyzed asymmetric Suzuki-Miyaura coupling reaction
      has been achieved. A number of functionalized biaryls were obtained in high
      yields and in moderate to high enantioselectivities. The existence of an ortho
      formyl group greatly improves the catalyst efficiency and permits further
      synthetic elaborations.

PMID- 21069985
TI  - Free-standing bimetallic nanorings and nanoring arrays made by on-wire
      lithography.
AB  - This paper describes a new strategy for synthesizing free-standing bimetallic
      nanorings and nanoring arrays based upon on-wire lithography and a galvanic
      replacement reaction. The strategy allows one to tune the diameter, length, and
      therefore aspect ratio of the nanorings. In addition, it can be used to produce
      arrays of nanorings in high yield with control over number and spacing.
      Spectroscopic studies and discrete dipole approximation calculations show that
      nanoring dimers exhibit greater surface enhanced Raman scattering than the
      analogous nanodisk dimers.

PMID- 21069986
TI  - Gold(I)-catalyzed cycloisomerization of beta-alkynylpropiolactones to substituted
      alpha-pyrones.
AB  - Substituted alpha-pyrones were straightforwardly synthesized in good to excellent
      yields by a new gold(I)-catalyzed rearrangement of beta-alkynylpropiolactones.

PMID- 21069987
TI  - Chain stiffness and attachment-dependent attraction between polyelectrolyte
      grafted colloids.
AB  - We report here the effects of chain stiffness and surface attachment on the
      effective interactions between polyelectrolyte-grafted colloidal particles in
      monovalent salt obtained using Monte Carlo simulations. Our approach involves
      computation of the distance-dependent potential of mean force between two
      polyelectrolyte-grafted colloidal particles treated at a coarse-grained
      resolution. Two chain stiffnesses, flexible and stiff, and two surface attachment
      modes, free and constrained, at low grafting densities are examined. PMF
      calculations across a range of surface and polyelectrolyte charge allows us to
      map out the strength and extent of the attractive and repulsive regime in the two
      dimensional charge space. We observe striking differences in the effects of chain
      stiffness between the two modes of attachment. When the chains are freely
      attached, the stiff-chains colloids exhibit a marginal reduction in the
      attraction compared to their flexible-chain counterparts. In contrast, when the
      chains are attached in a constrained manner, the colloids with stiff chains
      exhibit a significantly stronger attraction and a broader attractive regime
      compared to flexible-chain colloids. These differences in the effects of
      stiffness between the two attachment modes are explained in terms of differences
      in the energetic and entropic forces balancing adsorption of chains at their own
      surface versus chain extension to mediate bridging interactions across two
      particles. Our results thus underscore the importance of surface attachment of
      chains and its proper accounting in computational and experimental studies and
      suggests the mode of chain attachment as an additional control parameter for
      modulating intercolloid interactions for applications such as stabilization of
      colloidal systems and bottom-up self-assembly of nanostructures.

PMID- 21069988
TI  - Halide ions complex and deprotonate dipicolinamides and isophthalamides:
      assessment by mass spectrometry and UV-visible spectroscopy.
AB  - The F(-), Cl(-), and Br(-) binding selectivity of bis(p-nitroanilide)s of
      dipicolinic and isophthalic acids was studied by using competitive electrospray
      mass spectrometry and UV-Visible spectroscopy. Both hosts prefer binding Cl(-)
      over either F(-) or Br(-). Host deprotonation was observed to some extent in all
      experiments in which the host was exposed to halide ions. When F(-) was present,
      host deprotonation was often the major process, whereas little deprotonation was
      observed by Cl(-) or Br(-), which preferred complexation. A solution of either
      host changed color when mixed with a F(-), H(2)PO(4)(-), di- or triphenylacetate
      solution.

PMID- 21069989
TI  - Quantum-dot-sensitized solar cells fabricated by the combined process of the
      direct attachment of colloidal CdSe quantum dots having a ZnS glue layer and
      spray pyrolysis deposition.
AB  - We were able to attach CdSe quantum dots (QDs) having a ZnS inorganic glue layer
      directly to a mesoporous TiO(2) (mp-TiO(2)) surface by spray coating and thermal
      annealing. Quantum-dot-sensitized solar cells based on CdSe QDs having ZnS as the
      inorganic glue layer could easily transport generated charge carriers because of
      the intimate bonding between CdSe and mp-TiO(2). The application of spray
      pyrolysis deposition (SPD) to obtain additional CdSe layers improved the
      performance characteristics to V(oc) = 0.45 V, J(sc) = 10.7 mA/cm(2), fill factor
      = 35.8%, and power conversion efficiency = 1.7%. Furthermore, ZnS post-treatment
      improved the device performance to V(oc) = 0.57 V, J(sc) = 11.2 mA/cm(2), fill
      factor = 35.4%, and power conversion efficiency = 2.2%.

PMID- 21069990
TI  - Novel multiparametric approach to elucidate the surface amine-silanization
      reaction profile on fluorescent silica nanoparticles.
AB  - This Article addresses the important issue of the characterization of surface
      functional groups for optical bioassay applications. We use a model system
      consisting of spherical dye-doped silica nanoparticles (NPs) that have been
      functionalized with amine groups whereby the encapsulated cyanine-based near
      infrared dye fluorescence acts as a probe of the NP surface environment. This
      facilitates the identification of the optimum deposition parameters for the
      formation of a stable ordered amine monolayer and also elucidates the
      functionalization profile of the amine-silanization process. Specifically, we use
      a novel approach where the techniques of fluorescence correlation spectroscopy
      (FCS) and fluorescence lifetime measurement (FL) are used in conjunction with the
      more conventional analytical techniques of zeta potential measurement and Fourier
      transfer infrared spectroscopy (FTIR). The dynamics of the ordering of the amine
      layer in different stages of the reaction have been characterized by FTIR, FL,
      and FCS. The results indicate an optimum reaction time for the formation of a
      stable amine layer, which is optimized for further biomolecular conjugation,
      whereas extended reaction times lead to a disordered cross-linked layer. The
      results have been validated using an immunoglobulin (IgG) plate-based direct
      binding assay where the maximum number of IgG-conjugated aminated NPs were
      captured by immobilized anti-IgG antibodies for the NP sample corresponding to
      the optimized amine-silanization condition. Importantly, these results point to
      the potential of FCS and FL as useful analytical tools in diverse fields such as
      characterization of surface functionalization.

PMID- 21069992
TI  - Nicholas reactions in the construction of cyclohepta[de]naphthalenes and
      cyclohepta[de]naphthalenones. The total synthesis of microstegiol.
AB  - The application of the Nicholas reaction chemistry of 2,7-dioxygenated
      naphthalenes in the synthesis of cyclohepta[de]napthalenes and in the synthesis
      of (+/-)-microstegiol (1) is presented. The substitution profile of Nicholas
      monosubstitution (predominantly C-1) and disubstitution reactions (predominantly
      1,6-) on 2,7-dioxygenated napthalenes is reported. Application of a 1,8
      dicondensation product and selected C-1 monocondensation products to the
      construction of cyclohepta[de]naphthalenes by way of ring closing metathesis and
      intramolecular Friedel-Crafts reactions, respectively, is described. Deprotection
      of the C-7 oxygen function to the corresponding naphthol allows tautomerization
      to cyclohepta[de]naphthalene-1-ones upon seven-membered-ring closure in most
      cases, and replacement of the C-2 oxygen function in the naphthalene by a methyl
      group ultimately allows the synthesis of (+/-)-microstegiol.

PMID- 21069991
TI  - On the validity of Au-vinylidenes in the gold-catalyzed 1,2-migratory
      cycloisomerization of skipped propargylpyridines.
AB  - A mechanism of the Au-catalyzed cycloisomerization of propargylpyridines has been
      investigated. Both DFT computational and experimental results strongly support
      generation of a Au-carbene via a cyclization/proton transfer sequence over the
      previously proposed path involving a Au-vinylidene intermediate. For the beta-Si
      substituted Au-carbene (G = SiR(3)), a 1,2-Si migration was shown to be
      kinetically favored over a 1,2-H shift. This study highlights the importance of
      alternative pathways that could explain reactivities commonly attributed to an
      alkyne-vinylidene isomerization in Au catalysis.

PMID- 21069993
TI  - Photocatalytic events of CdSe quantum dots in confined media. Electrodic behavior
      of coupled platinum nanoparticles.
AB  - The electrodic behavior of platinum nanoparticles (2.8 nm diameter) and their
      role in influencing the photocatalytic behavior of CdSe quantum dots (3.4 nm
      diameter) has been evaluated by confining both nanoparticles together in
      heptane/dioctyl sulphosuccinate/water reverse micelles. The particles
      spontaneously couple together within the micelles via micellar exchange processes
      and thus facilitate experimental observation of electron transfer reactions
      inside the water pools. Electron transfer from CdSe to Pt is found to occur with
      a rate constant of 1.22 * 10(9) s(-1). With the use of methyl viologen (MV(2+))
      as a probe molecule, the role of Pt in the photocatalytic process is established.
      Ultrafast oxidation of the photogenerated MV(+*) radicals indicates that Pt acts
      as an electron sink, scavenging electrons from MV(+*) with a rate constant of 3.1
      * 10(9) s(-1). The electron transfer between MV(+*) and Pt, and a drastically
      lower yield of MV(+*) under steady state irradiation, confirms the ability of Pt
      nanoparticles to discharge electrons quickly. The kinetic details of photoinduced
      processes in CdSe-Pt assemblies and the electrodic behavior of Pt nanoparticles
      provide important information for the development of light energy conversion
      devices.

PMID- 21069995
TI  - Synthesis and characterization of A4[Re6Q8L6]@SiO2 red-emitting silica
      nanoparticles based on Re6 metal atom clusters (A = Cs or K, Q = S or Se, and L =
      OH or CN).
AB  - Metal atom clusters constitute very promising candidates as luminophores for
      applications in biotechnology because they are nanosized entities offering robust
      luminescence in the near-infrared field (NIR). However, they cannot be used as
      prepared for biological applications because of potential toxic effects and
      quenching of the clusters' luminescence in aqueous media, and they therefore need
      to be dispersed in a biocompatible matrix. We describe herein the encapsulation
      of octahedral rhenium clusters, denoted as A(4)[Re(6)Q(8)L(6)] (A = Cs or K, Q =
      S or Se, and L = OH or CN), in silica nanoparticles by a water-in-oil
      microemulsion process, paying particular attention to the clusters' stability.
      The obtained A(4)[Re(6)Q(8)L(6)]@SiO(2) nanoparticles are 30 nm in size with good
      monodispersity and a perfectly spherical shape, as shown by scanning electron
      microscopy (SEM). The presence of cluster units inside the silica matrix was
      evidenced by scanning transmission electron microscopy in annular dark-field mode
      (ADF-STEM). From the point of view of their optical properties, the
      A(4)[Re(6)Q(8)L(6)]@SiO(2) nanoparticles show red and NIR emission under UV
      excitation, even when dispersed in water. The evolution of the structural and
      luminescence properties of clusters before and after encapsulation was followed
      by Raman and photoluminescence spectroscopy.

PMID- 21069994
TI  - Preparation of stereodefined homoallylic amines from the reductive cross-coupling
      of allylic alcohols with imines.
AB  - Regio-, diastereo-, and enantioselective coupling reactions between imines and
      allylic alcohols have been developed. These coupling reactions deliver complex
      homoallylic amine products through a convergent C-C bond forming process that
      does not proceed through intermediate allylic organometallic reagents. In
      general, convergent coupling, by exposure of an allylic alkoxide to a preformed
      Ti-imine complex, occurs with allylic transposition in a predictable and
      stereocontrolled manner. While simple diastereoselection in these reactions is
      high, delivering anti-products with >=20:1 selectivity, the organometallic
      transformation described is compatible with a diverse range of functionality and
      substrates (including aliphatic and aromatic imines, allylic silanes,
      trisubstituted alkenes, vinyl- and aryl halides, trifluoromethyl groups,
      thioethers, and aromatic heterocycles). Alkene geometry of the products is a
      complex function of the allylic alcohol structure and is consistent with a
      mechanistic proposal based on syn-carbometalation followed by syn-elimination by
      way of a boat-like transition state geometry. Single asymmetric coupling
      reactions provide a means to translate the stereochemical information of the
      allylic alcohol to the homoallylic amine or to control diastereoselection in the
      coupling reactions of achiral allylic alcohols with chiral imines. Double
      asymmetric coupling reactions are also described that afford a unique means to
      control stereoselection in these complex convergent coupling processes. Finally,
      empirical models are proposed that are consistent with the observed
      stereochemical course of these coupling reactions en route to chiral homoallylic
      amines possessing di- or trisubstituted alkenes and anti- or syn- relative
      stereochemistry at the allylic and homoallylic positions.

PMID- 21069996
TI  - Ion-pair structure of vaporized ionic liquid studied by matrix-isolation FTIR
      spectroscopy with DFT calculations: a case of 1-ethyl-3-methylimidazolium
      trifluoromethanesulfonate.
AB  - The matrix-isolation infrared spectrum of a thermally evaporated ionic liquid, 1
      ethyl-3-methylimidazolium trifluoromethanesulfonate ([Emim][OTf]), was measured
      by FTIR spectroscopy and analyzed with the aid of DFT calculations. The main
      chemical species in the observed IR spectrum was mainly identified as the 1:1
      cation-anion pair, which corresponds to the second stable ion-pair structure
      bonded through five hydrogen bonds between three O atoms of the anion side and
      four H atoms of the cation.

PMID- 21069997
TI  - The quantum cutting of Tb(3+) in Ca(6)Ln(2)Na(2)(PO(4))(6)F(2) (Ln = Gd, La)
      under VUV-UV excitation: with and without Gd(3+).
AB  - The VUV-vis spectroscopic properties of Tb(3+) activated fluoro-apatite phosphors
      Ca(6)Ln(2-x)Tb(x)Na(2)(PO(4))(6)F(2) (Ln = Gd, La) were studied. The results show
      that phosphors Ca(6)Gd(2-x)Tb(x)Na(2)(PO(4))(6)F(2) with Gd(3+) ions as
      sensitizers have intense absorption in the VUV range. The emission color of both
      phosphors can be tuned from blue to green by changing the doping concentration of
      Tb(3+) under 172 nm excitation. The visible quantum cutting (QC) via cross
      relaxation between Tb(3+) ions was observed in cases with and without Gd(3+).
      Though QC can be realized in phosphors Ca(6)La(2-x)Tb(x)Na(2)(PO(4))(6)F(2), we
      found that Gd(3+)-containg phosphors have a higher QC efficiency, confirming that
      the Gd(3+) ion indeed plays an important role during the quantum cutting process.
      In addition, the energy transfer process from Gd(3+) to Tb(3+) as well as (5)D(3)
      (5)D(4) cross relaxation was investigated and discussed in terms of luminescence
      spectra and decay curves.

PMID- 21069998
TI  - Synthesis of extended nanoscale optical encoders.
AB  - An optical encoder is a device that uses an interrupted light source-sensor pair
      to map linear or rotational motion onto a periodic signal. Simple, inexpensive
      optical encoders are used for precise positioning in machines such as desktop
      printers, disk drives, and astronomical telescopes. A strand of DNA labeled with
      a series of Forster resonance energy transfer acceptor dyes can perform the same
      function at the nanometer scale, producing a periodic fluorescence signal that
      encodes the movement of a single donor-labeled molecular motor with high spatial
      and temporal resolution. Previous measurements of this type have employed
      encoders limited to five acceptor dyes, and hence five signal periods,
      restricting the range of motion that could be followed. Here we describe two
      methods for synthesizing double-stranded DNA containing several to hundreds of
      regularly spaced dyes on one strand. Distinct functional groups incorporated at
      the encoder ends enable tethering for single-molecule measurements.

PMID- 21069999
TI  - Enzyme-mediated site-specific antibody-protein modification using a ZZ domain as
      a linker.
AB  - A ZZ domain (ZZ) and alkaline phosphatase (AP), luciferase (Luc), or glucose
      oxidase (GOD) were conjugated using Sortase A (SrtA) from Staphylococcus aureus.
      The specific peptidyl linker for SrtA was genetically fused to the C-terminus of
      ZZ, and the other linker was fused to the N-terminus of AP, Luc, or GOD,
      respectively. The resultant proteins were obtained separately by bacterial
      expression. The recombinant peptide-tagged ZZ and AP, Luc, or GOD were site
      specifically conjugated by SrtA through the extra peptidyl linkers in vitro. The
      SrtA reaction had little influence on either the antibody-binding activity of the
      ZZ moiety or the enzymatic activity of AP, Luc, or GOD moieties of the
      conjugates. Additionally, antibody-ZZ-proteins were yielded easily by mixing
      antibody with ZZ-AP, ZZ-Luc, or ZZ-GOD, allowing their use in an enzyme-linked
      immunosorbent assay. These results suggest that the enzymatic approach with SrtA
      facilitates the construction of ZZ-proteins. Furthermore, mixing antibody and ZZ
      proteins produces a wide variety of antibody-ZZ-proteins.

PMID- 21070000
TI  - Radiosynthesis and biodistribution of a prosthetic group (18F-FENMA) conjugated
      to cyclic RGD peptides.
AB  - We have recently reported a new N-methylaminooxy-based prosthetic group for the
      site-selective introduction of 18F-fluorine under mild acidic aqueous conditions
      into model peptides functionalized with a Michael acceptor moiety. To further
      investigate the utility of this methodology, the radiosynthesis of two cyclic RGD
      peptides was carried out, and in vivo biodistribution and microPET studies were
      performed in tumor-bearing mice. A cyclic RGD peptide was functionalized with the
      Michael acceptors trans-beta-nitrostyrene carboxylic acid and 3
      vinylsulfonylpropionic acid. Radiolabeling was then performed with the prosthetic
      group O-(2-(2-[18F]fluoroethoxy)ethyl)-N-methylhydroxylamine (18F-FENMA) yielding
      the 18F-conjugates in moderate yields (8.5-12%). Biodistribution, blocking, and
      microPET imaging studies were performed in a mouse xenograft model. The
      vinylsulfonyl-modified conjugate demonstrated good in vitro plasma stability.
      Biodistribution and microPET studies revealed excellent tumor uptake with low
      background in key organs and renal elimination as the predominant route of
      excretion. Blocking studies with coinjected nonlabeled RGD peptide confirmed the
      in vivo specificity for the integrin alpha(v)beta3. On the other hand, 18F-FENMA
      nitrostyrene-RGD, although stable at conjugation pH 5, was found to rapidly
      degrade at physiological pH through loss of the 18F-prosthetic group.

PMID- 21070001
TI  - Synthesis and evaluation of 15-(4-(2-[18F]Fluoroethoxy)phenyl)pentadecanoic acid:
      a potential PET tracer for studying myocardial fatty acid metabolism.
AB  - 15-(4-(2-[18F]fluoroethoxy)phenyl)pentadecanoic acid ([18F]7) was synthesized as
      a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of
      [18F]7 was accomplished using a two-step reaction, starting with the
      corresponding tosylate ester, methyl 15-(4-(2
      (tosyloxy)ethoxy)phenyl)pentadecanoate (5), and gave the radiolabeled fatty acid,
      [18F]7 in a radiolabeling yield of 55-60% and a specific activity of >2000
      Ci/mmol (decay corrected to EOB). The biological evaluation of [18F]7 in rats
      displayed high uptake in heart (1.94%ID/g at 5 min), which was higher than the
      uptake (%ID/g) in blood, lung, muscle, pancreas, and brain. MicroPET studies of
      [18F]7 in Sprague-Dawley rats demonstrated excellent images of the myocardium
      when compared with [11C]palmitate images in the same animal. Moreover, the tracer
      kinetics of [18F]7 paralleled those seen with [11C]palmitate, with an early peak
      followed by biphasic washout. When compared to [11C]palmitate, [18F]7 exhibited a
      slower early clearance (0.17 +/- 0.01 vs 0.30 +/- 0.02, P < 0.0001) and a
      significantly higher late clearance (0.0030 +/- 0.0005 vs 0.0006 +/- 0.00013, P <
      0.01). These initial studies suggest that [18F]7 could be a potentially useful
      clinical PET tracer to assess abnormal myocardial fatty acid metabolism.

PMID- 21070002
TI  - Synthesis of triple-stranded complexes using bis(dipyrromethene) ligands.
AB  - The reaction of an alpha-free, beta,beta'-linked bis(dipyrromethene) ligand with
      Fe(3+) or Co(3+) led to noninterconvertible triple-stranded helicates and
      mesocates. In the present context, a stable alpha-free ligand 2 has been
      developed and complexation of ligands 1 and 2 with diamagnetic Co(3+), Ga(3+),
      and In(3+) has been studied. The triple-stranded M(2)1(3) (M = Ga, In) and
      M(2)2(3) (M = Co, Ga, In) complexes were characterized using matrix-assisted
      laser desorption ionization time-of-flight spectrometry, (1)H NMR and UV-vis
      spectroscopy, and X-ray crystallography. Again, the (1)H NMR analysis showed that
      both the triple-stranded helicates and mesocates were generated in this metal
      directed assembly. Consistent with our previous finding on coordinatively inert
      Co(3+) complexes, variable-temperature NMR spectroscopy indicated that the triple
      stranded helicate and mesocate of labile In(3+) did not interconvert in solution,
      either. However, the diastereoselectivity of the M(2)2(3) complexes was found to
      improve with an increase in the reaction temperature. Taken together, this study
      complements the coordination chemistry of poly(dipyrromethene) ligands and
      provides further insight into the formation of helicates versus mesocates.

PMID- 21070004
TI  - A family of 3d-4f octa-nuclear [Mn(III)(4)Ln(III)(4)] wheels (Ln = Sm, Gd, Tb,
      Dy, Ho, Er, and Y): synthesis, structure, and magnetism.
AB  - We present the syntheses, crystal structures, and magnetochemical
      characterizations for a family of isostructural [Mn(4)Ln(4)] compounds (Ln = Sm,
      Gd, Tb, Dy, Ho, Er, and Y). They were prepared from the reactions of formic acid,
      propionic acid, N-n-butyl-diethanolamine, manganese perchlorate, and lanthanide
      nitrates under the addition of triethylamine in MeOH. The compounds possess an
      intriguing hetero-octanuclear wheel structure with four Mn(III) and four Ln(III)
      ions alternatively arranged in a saddle-like ring, where formate ions act as key
      carboxylate bridges. In the lattice, the molecules stack into columns in a quasi
      hexagonal arrangement. Direct current (dc) magnetic susceptibility measurements
      indicated the depopulation of the Stark components at low temperature and/or very
      weak antiferromagnetic interactions between magnetic centers. The zero-field
      alternating current (ac) susceptibility studies revealed that the compounds
      containing Sm, Tb, and Dy showed frequency-dependent out-of-phase signals,
      indicating they are single-molecule magnets (SMMs). Magnetization versus applied
      dc field sweeps on a single crystal of the Dy compound down to 40 mK exhibited
      hysteresis depending on temperatures and field sweeping rates, further confirming
      that the Dy compound is a SMM. The magnetization dynamics of the Sm and Y
      compounds investigated under dc fields revealed that the relaxation of the Sm
      compound is considered to be dominated by the two-phonon (Orbach) process while
      the Y compound displays a multiple relaxation process.

PMID- 21070003
TI  - Scavenger receptors mediate cellular uptake of polyvalent oligonucleotide
      functionalized gold nanoparticles.
AB  - Mammalian cells have been shown to internalize oligonucleotide-functionalized
      gold nanoparticles (DNA-Au NPs or siRNA-Au NPs) without the aid of auxiliary
      transfection agents and use them to initiate an antisense or RNAi response.
      Previous studies have shown that the dense monolayer of oligonucleotides on the
      nanoparticle leads to the adsorption of serum proteins and facilitates cellular
      uptake. Here, we show that serum proteins generally act to inhibit cellular
      uptake of DNA-Au NPs. We identify the pathway for DNA-Au NP entry in HeLa cells.
      Biochemical analyses indicate that DNA-Au NPs are taken up by a process involving
      receptor-mediated endocytosis. Evidence shows that DNA-Au NP entry is primarily
      mediated by scavenger receptors, a class of pattern-recognition receptors. This
      uptake mechanism appears to be conserved across species, as blocking the same
      receptors in mouse cells also disrupted DNA-Au NP entry. Polyvalent nanoparticles
      functionalized with siRNA are shown to enter through the same pathway. Thus,
      scavenger receptors are required for cellular uptake of polyvalent
      oligonucleotide functionalized nanoparticles.

PMID- 21070005
TI  - Expression of Lactobacillus reuteri Pg4 collagen-binding protein gene in
      Lactobacillus casei ATCC 393 increases its adhesion ability to Caco-2 cells.
AB  - The collagen-binding protein gene cnb was cloned from the probiotic Lactobacillus
      reuteri strain Pg4. The DNA sequence of the cnb gene (792 bp) has an open reading
      frame encoding 263 amino acids with a calculated molecular weight of 28.5 kDa.
      The cnb gene was constructed so as to constitutively express under the control of
      the Lactococcus lactis lacA promoter and was transformed into Lactobacillus casei
      ATCC 393, a strain isolated from dairy products with poor ability to adhere to
      intestinal epithelial cells. Confocal immunofluorescence microscopic and flow
      cytometric analysis of the transformed strain Lb. casei pNZ-cnb indicated that
      Cnb was displayed on its cell surface. Lb. casei pNZ-cnb not only showed a higher
      ability to adhere to Caco-2 cells but also exhibited a higher competition ability
      against Escherichia coli O157:H7 and Listeria monocytogenes adhesion to Caco-2
      cells than Lb. casei ATCC 393. 

PMID- 21070006
TI  - Manipulating graphene mobility and charge neutral point with ligand-bound
      nanoparticles as charge reservoir.
AB  - The high carrier mobility of graphene makes it an attractive candidate for future
      electronic device applications.(1) In SiO2/Si-supported graphene devices, the
      mobility typically varies from 2000 to ~2,0000 cm(2) V(-1) s(-1).(2) By removing
      SiO2,(3,4) much higher mobility (2 * 10(5) cm(2) V(-1) s(-1) in the latter) has
      been obtained, suggesting the importance of the Coulomb scattering in graphene
      transport. Although such elaborate device fabrication is clearly effective, the
      mobility of finished devices is fixed thereafter and can vary from device to
      device. In this work, we first demonstrate a significant enhancement in carrier
      mobility in SiO2-supported graphene decorated with a layer of ligand-bound
      nanoparticles (NPs) such as iron oxide, titanium dioxide, or cadmium selenide
      acting as a charge reservoir. By transferring charges between graphene and the NP
      reservoir through the molecules, we show a remarkable reversible tunability in
      mobility (4000-19000 cm(2) V(-1) s(-1)) in the same device, which unambiguously
      proves that the charged impurity scattering is the prevailing mechanism for
      graphene mobility. In addition, the charge neutral point or the Dirac point can
      also be independently tuned over a wide gate voltage range. The reversible tuning
      is useful for fabricating large-area graphene devices such as nonvolatile memory
      with enhanced sensitivity.

PMID- 21070007
TI  - Collective dipolar interactions in self-assembled magnetic binary nanocrystal
      superlattice membranes.
AB  - Co-assembly of two types of nanocrystals (NCs) into binary NC superlattices
      (BNSLs) provides a solution-based, inexpensive way to create novel metamaterials
      with rationally designed properties. The fundamental challenge is to probe and
      understand the nature and extent of complex interparticle interactions present in
      BNSLs, which can lead to collective properties that differ from their dispersed
      constituents or phase-separated counterparts. Here, we report the growth and
      magnetic characterization of large-area (~1 cm(2)) BNSL membranes self-assembled
      from distinct magnetic NCs at the liquid-air interface. The resulting BNSL
      membranes exhibit a single-phase-like magnetization alignment process, which is
      not observed in the phase-separated NC mixtures having the same stoichiometry.
      This single-phase-like magnetic behavior is attributed to the collective
      interparticle dipolar interactions between two NC components in BNSLs,
      corroborated by calculation of the random dipolar fields as well as Monte Carlo
      simulation. The collective magnetic properties are demonstrated in magnetic BNSL
      membranes having different structures (stoichiometry) and different NC
      combinations.

PMID- 21070008
TI  - Effect of nitrogen doping on the mechanical properties of carbon nanotubes.
AB  - We report on the usage of a simple microfabricated device that works in
      conjunction with a quantitative Nanoindenter within a scanning electron
      microscope (SEM) chamber, for the in situ quantitative tensile testing of
      individual catalytically grown pristine and nitrogen-doped multiwall carbon
      nanotubes (MWNTs). The two types of MWNTs were found to possess similar strengths
      but different load-bearing abilities owing to the differences in their wall
      structures. Also, stress versus strain curves and fracture surfaces showed that
      while the pristine MWNTs deform and fail in a brittle fashion, the nitrogen-doped
      MWNTs deform plastically to varying degrees prior to failure. High resolution
      transmission electron microscope (TEM) images of the nitrogen-doped MWNT fracture
      specimens showed the presence of regions of reduced cross-section areas and kinks
      in close proximity to the fracture surfaces. The presence of nitrogen atoms in
      the graphitic sheets was assumed to have led to the formation of kinks whose
      motion induced by straining could have resulted in the plastic deformation of the
      carbon nanotubes.

PMID- 21070009
TI  - Epiafzelechin from the root bark of Cassia sieberiana: detection by DART mass
      spectrometry, spectroscopic characterization, and antioxidant properties.
AB  - The root bark of Cassia sieberiana was analyzed using direct analysis in real
      time mass spectrometry, and a main flavonoid component with an [M + H](+) mass of
      275 was identified. The flavonoid, epiafzelechin, was isolated and fully
      characterized with the concerted use of NMR spectroscopy, circular dichroism, and
      optical rotation. Electronic circular dichroism and optical rotation TDDFT
      calculations were also performed, and their agreement with the experimental
      results confirmed the enantiomeric identity of the isolated natural product. The
      antioxidant activity of the compound was also investigated.

PMID- 21070010
TI  - Macrophyllionium and macrophyllines A and B, oxindole alkaloids from Uncaria
      macrophylla.
AB  - An unusual oxindole alkaloid inner salt, macrophyllionium (1), and a pair of new
      tetracyclic oxindole alkaloids, macrophyllines A (2) and B (3), together with six
      known alkaloids, were isolated from the aerial parts of Uncaria macrophylla.
      Corynantheidine (8) exhibited moderate cytotoxicity against HL-60 and SW480 cells
      with IC(50) values of 13.96 and 23.28 MUM, respectively. Dihydrocorynantheine (9)
      exhibited significant vasodilating activity against phenylephrine-induced
      contraction in rat thoracic aorta rings (IC(50) = 6.73 MUg/mL). In addition,
      compounds 2, 6, and 9 showed weak inhibitory action on KCl-induced contraction.

PMID- 21070012
TI  - Interconnecting gold islands with DNA origami nanotubes.
AB  - Scaffolded DNA origami has recently emerged as a versatile, programmable method
      to fold DNA into arbitrarily shaped nanostructures that are spatially
      addressable, with sub-10-nm resolution. Toward functional DNA nanotechnology, one
      of the key challenges is to integrate the bottom-up self-assembly of DNA origami
      with the top-down lithographic methods used to generate surface patterning. In
      this report we demonstrate that fixed length DNA origami nanotubes, modified with
      multiple thiol groups near both ends, can be used to connect surface patterned
      gold islands (tens of nanometers in diameter) fabricated by electron beam
      lithography (EBL). Atomic force microscopic imaging verified that the DNA origami
      nanotubes can be efficiently aligned between gold islands with various
      interisland distances and relative locations. This development represents
      progress toward the goal of bridging bottom-up and top-down assembly approaches. 

PMID- 21070013
TI  - Polycyclic imide derivatives: synthesis and effective tuning of lowest unoccupied
      molecular orbital levels through molecular engineering.
AB  - A series of fluoranthene-fused imide derivatives were facilely developed through
      a Diels-Alder reaction followed by decarbonylation. The investigation of their
      photophysical and electrochemical properties demonstrated that their LUMO levels
      were effectively tuned from -3.2 to -3.8 eV through the introduction of a fused
      imide unit, which provides a platform to design new air-stable and solution
      processable n-type materials.

PMID- 21070014
TI  - Indium-promoted chemo- and diastereoselective allylation of alpha,beta-epoxy
      ketones with potassium allyltrifluoroborate.
AB  - A practical method for the chemo- and diastereoselective allylation of alpha,beta
      epoxy ketones has been developed by using the convenient air and moisture stable
      reagent potassium allyltrifluoroborate. Indium metal was found to promote
      addition in stoichiometric or catalytic amounts, to afford alpha,beta
      epoxyhomoallylic tertiary alcohols in high yields and diastereoselectivities,
      without competing ring-scission of the epoxide.

PMID- 21070015
TI  - Biexcitonic fine structure of CdSe nanocrystals probed by polarization-dependent
      two-dimensional photon echo spectroscopy.
AB  - The spectroscopy of colloidal CdSe nanocrystals is investigated using two
      dimensional photon echo (2DPE) spectroscopy with copolarized and cross-polarized
      pulse sequences. Clearly resolved excited state absorption features are observed
      to beat at the frequency of the longitudinal-optical phonon, and the phase of
      this beating is found to be polarization-dependent. A simulation is performed
      using the excitonic and biexcitionic fine structure states predicted by theory,
      and the polarization-dependent beating allows each feature to be assigned to a
      particular excited state absorption pathway. Owing to their circularly polarized
      selection rules, the polarization-dependent 2DPE technique provides valuable
      insights into the spectroscopy of quantum dots. In particular, transient
      absorption features observed in pump-probe studies of CdSe quantum dots can now
      be assigned to specific fine structure transitions to the ground state biexciton.

PMID- 21070016
TI  - Gold(III)-catalyzed halogenation of aromatic boronates with N-halosuccinimides.
AB  - Aromatic boronates bearing halogen substituents in the aromatic ring can be
      synthesized by AuCl(3)-catalyzed halogenations with N-halosuccinimides.

PMID- 21070017
TI  - Antiradical activity, phenolics profile, and hydroxymethylfurfural in espresso
      coffee: influence of technological factors.
AB  - The influence of technological factors (decaffeination, brew volume, coffee
      species, and roast degree) on antiradical activity and phenolics content of
      espresso coffee is described. The screenings of phenolics profile and other
      compounds (caffeine and trigonelline), as well as the quantification of
      hydroxymethylfurfural, were performed by LC-DAD-ESI-MS. Significantly lower (p <
      0.05) scavenging activities and phenolics contents were found in decaffeinated
      espressos when compared with regular ones (32 vs 38% and 324 vs 410 mg/30 mL cup,
      respectively). A long espresso (70 mL) offers more than twice the phenolics
      amount of a short one (20 mL). Robusta brews showed higher (p < 0.05) antiradical
      activity and phenolic contents than arabica ones, for all roast degrees (light,
      medium, and dark). No significant differences (p > 0.05) were observed for
      scavenging activities of differently roasted robusta brews, whereas an increase
      in medium-dark brews was observed for arabica samples. Total phenolics in robusta
      espressos decreased (p < 0.05) with the increase of roast degree, but no
      significant differences (p > 0.05) were found between arabica espressos from
      different roasts. By LC-DAD-ESI-MS, 23 hydroxycinnamic derivatives were found,
      including chlorogenic acids, lactones, and cinnamoyl-amino acid conjugates. The
      amount of each compound was differently affected by species and roast. Robusta
      brews presented superior levels of caffeine and chlorogenic acids, whereas
      arabica ones contained more trigonelline. Hydroxymethylfurfural contents in the
      brew (30 mL) varied from 2.60 to 0.84 mg for light- and dark-roasted arabicas and
      from 1.29 to 0.68 mg for light- and dark-roasted robustas, respectively. 

PMID- 21070018
TI  - Reactions of terminal polyynes with benzyl azide.
AB  - Terminal di-, tri-, tetra-, and pentaynes substituted with a variety of
      functional groups react with benzyl azide in the presence of CuSO(4).5H(2)O and
      ascorbic acid to give derivatives of 4-ethynyl-, 4-butadiynyl-, 4-hexatriynyl-,
      and 4-octatetraynyl-1,2,3-triazoles in moderate to good yields. These reactions
      appear to proceed regioselectively, and functionalization occurs exclusively at
      the terminal alkyne moiety. As well, no evidence of multiple azide additions to
      the polyyne framework is observed. X-ray crystallographic analysis of nine
      derivatives is used to document the regioselectivity of the reaction as well as
      outline structural characteristics of the 1,2,3-triazole products.

PMID- 21070019
TI  - Thermodynamics of grape and wine tannin interaction with polyproline:
      implications for red wine astringency.
AB  - The astringency of red wine is largely due to the interaction between wine
      tannins and salivary proline-rich proteins and is known to change as wine ages.
      To further understand the mechanisms behind wine astringency change over time,
      thermodynamics of the interactions between poly(l-proline) (PLP) and grape seed
      and skin tannins (preveraison (PV) and commercially ripe) or Shiraz wine tannins
      (2 years old and 9-10 years old) was analyzed using isothermal titration
      calorimetry (ITC). The nature of these interactions varied with changes to the
      tannin structure that are associated with maturation. The change in enthalpy
      associated with hydrophobic interaction and hydrogen bonding decreased with
      tannin age and the stoichiometry of binding indicated that grape tannins
      associated with more proline residues than wine tannins, irrespective of
      molecular size. These results could provide an explanation for the observed
      change in wine astringency quality with age. 

PMID- 21070020
TI  - Diruthenium compounds bearing equatorial fc-containing ligands: synthesis and
      electronic structure.
AB  - Previously, the synthesis of compounds Ru(2)(D(3,5-Cl(2)Ph)F)(4-n)(O(2)CFc)(n)Cl
      (n = 1, 3a; 2, 4a), where D(3,5-Cl(2)Ph)F is N,N'-di(3,5
      dichlorophenyl)formamidinate, from the carboxylate exchange reactions between
      Ru(2)(D(3,5-Cl(2)Ph)F)(4-n)(OAc)(n)Cl and ferrocene carboxylic acid was
      communicated. Reported herein is the preparation of analogous compounds
      Ru(2)(DmAniF)(4-n)(O(2)CFc)(n)Cl (n = 1, 3b; 2, 4b), where DmAniF is N,N'-di(3
      methoxyphenyl)formamidinate, from Ru(2)(DmAniF)(4-n)(OAc)(n)Cl. Compounds 3 and 4
      were characterized with various techniques including X-ray structural
      determinations of 3a and 4a. Voltammetric behaviors of compounds 3 and 4 were
      investigated, and stepwise one-electron ferrocene oxidations were observed for
      both compounds 4a and 4b. Spectral analysis of the monocations [4](+) indicated
      that they are the Robin-Day class II mixed valent [Fc...Fc](+) species.
      Measurement and fitting of magnetic data (chiT) of 4a between 2 and 300 K
      revealed a typical zero-field splitting of a S = 3/2 center with D = 77 cm(-1),
      while those of [4a]BF(4) are consistent with the presence of S = 3/2 (Ru(2)) and
      S = 1/2 (Fc(+)) centers that are weakly coupled (zJ = -0.76 cm(-1)).

PMID- 21070021
TI  - Homogeneous Ni catalysts for H2 oxidation and production: an assessment of
      theoretical methods, from density functional theory to post Hartree-Fock
      correlated wave-function theory.
AB  - A systematic assessment of theoretical methods applicable to the accurate
      characterization of catalytic cycles of homogeneous catalysts for H(2) oxidation
      and evolution is reported. The key elementary steps involve heterolytic cleavage
      of the H-H bond and formation/cleavage of Ni-H and N-H bonds. In the context of
      density functional theory (DFT), we investigated the use of functionals in the
      generalized gradient approximation (GGA) as well as hybrid functionals. We
      compared the results with wave-function theories based on perturbation theory
      (MP2 and MP4) and on coupled-cluster expansions [CCD, CCSD, and CCSD(T)]. Our
      findings indicate that DFT results based on Perdew correlation functionals are in
      semiquantitative agreement with the CCSD(T) results, with deviations of only a
      few kilocalories/mole. On the other hand, the B3LYP functional is not even in
      qualitative agreement with CCSD(T). Surprisingly, the MP2 results are found to be
      extremely poor, in particular for the diproton Ni(0) and dihydride Ni(IV) species
      on the reaction potential energy surface. The Hartree-Fock reference wave
      function in MP2 theory gives a poor reference state description for these states
      that are electron rich on Ni, giving rise to erroneous MP2 energies. We present a
      detailed potential-energy diagram for the oxidation of H(2) by these catalysts
      after accounting for the effects of solvation, as modeled by a polarizable
      continuum, and of free energy estimated at the harmonic level of theory.

PMID- 21070022
TI  - Hot injection dynamics: design mechanisms and ideas.
AB  - A minimal quantum mechanical model for efficient molecular capture of photon
      energy is presented. The model is constructed from a bright electronic state
      which is accessed by a photoinduced transition from the ground state and an
      acceptor excited state which stores the photoenergy. The model permits rational
      design of the bright and acceptor electronic states to improve the capture of
      solar energy. The main design factors are analyzed through examples.

PMID- 21070024
TI  - Overall charge and local charge density of pectin determines the enthalpic and
      entropic contributions to complexation with beta-lactoglobulin.
AB  - The complex formation between beta-lactoglobulin and pectins of varying overall
      charge and local charge density were investigated. Isothermal titration
      calorimetry experiments were carried out to determine the enthalpic contribution
      to the complex formation at pH 4.25 and various ionic strengths. Complex
      formation was found to be an exothermic process for all conditions. Combination
      with previously published binding constants by Sperber et al. (Sperber, B. L. H.
      M.; Cohen Stuart, M. A.; Schols, H. A.; Voragen, A. G. J.; Norde, W.
      Biomacromolecules 2009, 10, 3246-3252) allows for the determination of the
      changes in the Gibbs energy and the change in entropy of the system upon complex
      formation between beta-lactoglobulin and pectin. The local charge density of
      pectin is found to determine the balance between enthalpic and entropic
      contributions. For a high local charge density pectin, the main contribution to
      the Gibbs energy is of an enthalpic nature, supported by a favorable entropy
      effect due to the release of small counterions. A pectin with a low local charge
      density has a more even distribution of the enthalpic and entropic part to the
      change of the Gibbs energy. The enthalpic part is reduced due to the lower charge
      density, while the relative increase of the entropic contribution is thought to
      be caused by a change in the location of the binding place for pectin on the beta
      lactoglobulin molecule. The association of the hydrophobic methyl esters on
      pectin with an exposed hydrophobic region on beta-lg results in the release of
      water molecules from the hydrophobic region and surrounding the methyl esters of
      the pectin molecule. An increase in the ionic strength decreases the enthalpic
      contribution due to the shielding of electrostatic attraction in favor of the
      entropic contribution, supporting the idea that the release of water molecules
      from hydrophobic areas plays a part in the complex formation.

PMID- 21070023
TI  - Origins of stereoselectivity in the alpha-alkylation of chiral hydrazones.
AB  - Density functional theory calculations and experiment reveal the origin of
      stereoselectivity in the deprotonation-alkylation of chiral N-amino cyclic
      carbamate (ACC) hydrazones. When the ACC is a rigid, camphor-derived carbamate,
      the two conformations of the azaenolate intermediate differ in energy due to
      conformational effects within the oxazolidinone ring and steric interactions
      between the ACC and the azaenolate. An electrophile adds selectively to the less
      hindered pi-face of the azaenolate. Although it was earlier reported that use of
      ACC auxiliaries led to alpha-alkylated ketones with er values of 82:18 to 98:2,
      B3LYP calculations predict higher stereoselectivity. Direct measurement of the dr
      of an alkylated hydrazone prior to removal of the auxiliary confirms this
      prediction; the removal of the auxiliary under the reported conditions can
      compromise the overall stereoselectivity of the process.

PMID- 21070025
TI  - Antifungal cyclic peptides from Psammosilene tunicoides.
AB  - Three new cyclic peptides, tunicyclins B-D, and a known cyclic peptide,
      psammosilenin B, were isolated from the root of Psammosilene tunicoides. The
      structures of new cyclic peptides were elucidated by extensive NMR and MS
      analysis. Tunicyclin B contains an unusual alpha,beta-dehydrotryptophan (Delta(Z)
      Trp) residue, previously reported from marine sponges and bacteria. Tunicyclin D
      showed a broad spectrum of antifungal activity against Candida albicans (SC5314),
      Candida albicans (Y0109), Candida tropicalis, Candida parapsilosis, and
      Cryptococcus neoformans (BLS108) with MIC(80) values of 4.0, 16.0, 0.25, 1.0, and
      1.0 MUg mL(-1), respectively.

PMID- 21070027
TI  - Synthesis of functionalized chromans by PnBu3-catalyzed reactions of
      salicylaldimines and salicylaldehydes with allenic ester.
AB  - P(n)Bu(3)-catalyzed cyclization reactions of salicylaldimines and
      salicylaldehydes with ethyl 2,3-butadienoate gave the corresponding
      functionalized chromans in moderate to good yields in THF under mild conditions.
      The new reaction provides a new method for the synthesis of biologically active
      chroman products.

PMID- 21070026
TI  - Mixed stimuli-responsive magnetic and gold nanoparticle system for rapid
      purification, enrichment, and detection of biomarkers.
AB  - A new diagnostic system for the enrichment and detection of protein biomarkers
      from human plasma is presented. Gold nanoparticles (AuNPs) were surface-modified
      with a diblock copolymer synthesized using reversible addition-fragmentation
      chain transfer (RAFT) polymerization. The diblock copolymer contained a thermally
      responsive poly(N-isopropylacrylamide) (pNIPAAm) block, a cationic amine
      containing block, and a semi-telechelic PEG2-biotin end group. When a mixed
      suspension of 23 nm pNIPAAm-modified AuNPs was heated with pNIPAAm-coated 10 nm
      iron oxide magnetic nanoparticles (mNPs) in human plasma, the thermally
      responsive pNIPAAm directed the formation of mixed AuNP/mNP aggregates that could
      be separated efficiently with a magnet. Model studies showed that this mixed
      nanoparticle system could efficiently purify and strongly enrich the model
      biomarker protein streptavidin in spiked human plasma. A 10 ng/mL streptavidin
      sample was mixed with the biotinylated pNIPAAm-modified AuNPs and magnetically
      separated in the mixed nanoparticle system with pNIPAAm mNPs. The aggregates were
      concentrated into a 50-fold smaller fluid volume at room temperature where the
      gold nanoparticle reagent redissolved with the streptavidin target still bound.
      The concentrated gold-labeled streptavidin could be subsequently analyzed
      directly using lateral flow immunochromatography. This rapid capture and
      enrichment module thus utilizes the mixed stimuli-responsive nanoparticle system
      to achieve concentration of a gold-labeled biomarker that can be directly
      analyzed using lateral flow or other rapid diagnostic strategies.

PMID- 21070029
TI  - Bridging the gap between electrochemical and organometallic activation: benzyl
      chloride reduction at silver cathodes.
AB  - Integration of voltammetry, surface-enhanced Raman spectroscopy (SERS), and
      density functional theory (DFT) has allowed unraveling the mechanistic origin of
      the exceptional electrocatalytic properties of silver cathodes during the
      reduction of benzyl chloride. At inert electrodes the initial reduction proceeds
      through a concerted direct electron transfer yielding a benzyl radical as the
      first intermediate. Conversely, at silver electrodes it involves an uphill
      preadsorption of benzyl chloride onto the silver cathode. Reduction of this
      adduct affords a species tentatively described as a distorted benzyl radical
      anion stabilized by the silver surface. This transient species rapidly evolves to
      yield ultimately a benzyl radical bound onto the silver surface, the latter being
      reduced into a benzyl-silver anionic adduct which eventually dissociates into a
      free benzyl anion at more negative potentials. Within this framework, the
      exceptional electrocatalytic properties of silver cathodes stem from the fact
      that they drastically modify the mechanism of the 2e-reduction pathway through a
      direct consequence of the electrophilicity of silver cathode surfaces toward
      organic halides. This mechanism contrasts drastically with any of those
      tentatively invoked previously, and bridges classical electroreduction mechanisms
      and oxidative additions similar to those occurring during organometallic
      homogeneous activation of organic halides by low-valent transition-metal
      complexes.

PMID- 21070031
TI  - Nitrotetrazolate-2N-oxides and the strategy of N-oxide introduction.
AB  - The first anionic tetrazole-2N-oxide has been prepared by mild aqueous oxidation
      of easily prepared 5-nitrotetrazole with commercially available oxone in high
      yields. The result of protonating 5-nitrotetrazolate-2N-oxide has been identified
      as a hydroxytetrazole, and the nitrogen-rich salts including ammonium,
      hydroxylammonium, guanidinium, aminoguanidinum, diaminoguanidinium, and
      triaminoguanidinium have been prepared and characterized. When compared to the
      nitrogen-rich salts of nitrotetrazole, the nitrogen-rich salts of nitrotetrazole
      2N-oxide show superior energetic performance as calculated by the EXPLO5 computer
      code, using heats of formation calculated using the CBS-4M level of quantum
      mechanical theory. The impact, friction, and electrical spark sensitivities of
      the nitrogen-rich nitrotetrazolate-2N-oxides were measured and cover the whole
      range from sensitive to insensitive energetic materials.

PMID- 21070032
TI  - Supramolecular chromotropism of the crystalline phases of 4,5,6,7
      tetrafluorobenzo-2,1,3-telluradiazole.
AB  - The remarkable effect that secondary bonding interactions can have on the
      macroscopic properties of a material is illustrated by two polymorphs of the
      title compound. The phase which is most stable under ambient pressure and
      temperature consists of puckered supramolecular ribbon polymers assembled by Te-
      N secondary bonding interactions and displays a characteristic red-orange color.
      A second yellow phase consists of ribbons with alternating short and long
      intermolecular Te--N secondary bonding distances and is metastable; at 127 
      degrees C the material undergoes an exothermic irreversible transition to the red
      polymorph. A third phase consists of pyridine-solvated supramolecular dimers; it
      is also yellow and transforms into the red phase after the crystals effloresce.
      Computational DFT studies indicate that the observed changes in optical
      properties are related to intermolecular mixing of pi orbitals enabled by the
      supramolecular interactions and the symmetry of the supramolecular synthon.

PMID- 21070030
TI  - Sulfur versus iron oxidation in an iron-thiolate model complex.
AB  - In the absence of base, the reaction of [Fe(II)(TMCS)]PF6 (1, TMCS = 1-(2
      mercaptoethyl)-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane) with peracid
      in methanol at -20  degrees C did not yield the oxoiron(IV) complex (2,
      [Fe(IV)(O)(TMCS)]PF6), as previously observed in the presence of strong base
      (KO(t)Bu). Instead, the addition of 1 equiv of peracid resulted in 50%
      consumption of 1. The addition of a second equivalent of peracid resulted in the
      complete consumption of 1 and the formation of a new species 3, as monitored by
      UV-vis, ESI-MS, and Mossbauer spectroscopies. ESI-MS showed 3 to be formulated as
      [Fe(II)(TMCS) + 2O](+), while EXAFS analysis suggested that 3 was an O-bound
      iron(II)-sulfinate complex (Fe-O = 1.95 A, Fe-S = 3.26 A). The addition of a
      third equivalent of peracid resulted in the formation of yet another compound, 4,
      which showed electronic absorption properties typical of an oxoiron(IV) species.
      Mossbauer spectroscopy confirmed 4 to be a novel iron(IV) compound, different
      from 2, and EXAFS (Fe?O = 1.64 A) and resonance Raman (nu(Fe?O) = 831 cm(-1))
      showed that indeed an oxoiron(IV) unit had been generated in 4. Furthermore, both
      infrared and Raman spectroscopy gave indications that 4 contains a metal-bound
      sulfinate moiety (nu(s)(SO2) ~ 1000 cm (-1), nu(as)(SO2) ~ 1150 cm (-1)).
      Investigations into the reactivity of 1 and 2 toward H(+) and oxygen atom
      transfer reagents have led to a mechanism for sulfur oxidation in which 2 could
      form even in the absence of base but is rapidly protonated to yield an
      oxoiron(IV) species with an uncoordinated thiol moiety that acts as both oxidant
      and substrate in the conversion of 2 to 3.

PMID- 21070033
TI  - Incorporation of piperazino functionality into 1,3-disubstituted urea as the
      tertiary pharmacophore affording potent inhibitors of soluble epoxide hydrolase
      with improved pharmacokinetic properties.
AB  - The inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising
      new therapy in the treatment of hypertension, inflammation, and other disorders.
      However, the problems of limited water solubility, high melting point, and low
      metabolic stability complicated the development of 1,3-disubstituted urea-based
      sEH inhibitors. The current study explored the introduction of the substituted
      piperazino group as the tertiary pharmacophore, which resulted in substantial
      improvements in pharmacokinetic parameters over previously reported 1
      adamantylurea based inhibitors while retaining high potency. The SAR studies
      revealed that the meta- or para-substituted phenyl spacer and N(4)-acetyl or
      sulfonyl substituted piperazine were optimal structures for achieving high
      potency and good physical properties. The 1-(4-(4-(4-acetylpiperazin-1
      yl)butoxy)phenyl)-3-adamantan-1-yl urea (29c) demonstrated excellent in vivo
      pharmacokinetic properties in mice: T1/2 =14 h, Cmax = 84 nM, AUC = 40 200
      nM.min, and IC50 = 7.0 nM against human sEH enzyme. 

PMID- 21070034
TI  - Alumina-supported Cu(II), a versatile and recyclable catalyst for regioselective
      ring opening of aziridines and epoxides and subsequent cyclization to
      functionalized 1,4-benzoxazines and 1,4-benzodioxanes.
AB  - An easily accessible catalyst, alumina-supported copper(II), efficiently
      catalyzes the ring opening of aziridines and epoxides followed by cyclization of
      the corresponding intermediate to produce a variety of functionalized 1,4
      benzoxazines and 1,4-benzodioxanes, respectively, in one pot without any ligand
      in high yields. The ring cleavages of aziridines and epoxides are highly
      regioselective. The catalyst is inexpensive, non-air-sensitive, environmentally
      friendly, and recyclable. The function of the catalyst and the reaction pathway
      are postulated. This protocol is successfully utilized for the formation of three
      carbon-heteroatom bonds, namely, C-O, C-N, and C-S, in one pot.

PMID- 21070035
TI  - Inclusion of terpenoid plant extracts in lipid bilayers investigated by molecular
      dynamics simulations.
AB  - The plant Perilla frutescens is widely employed in Asian medicine. The active
      components of Perilla include cyclic terpenes, which have a diverse range of
      antimicrobial, anticancer, sedative, and anti-inflammatory properties, hinting at
      a membrane-mediated mechanism of action. We have used molecular dynamics (MD)
      simulations and isothermal titration calorimetry (ITC) to investigate the
      interaction of four terpenes with model lipid bilayers. The ITC and MD data are
      mostly in accordance. The terpenes partition into membranes, pack along the lipid
      tails, and alter bilayer structure and dynamics. Three of the four molecules
      could cross the bilayer. The carboxylate-group-containing terpene modifies
      headgroup repulsion and increases the area per lipid by more than 10%, in a
      manner reminiscent of membrane-thinning peptides and solvents such as DMSO. Our
      results support the possibility that at least some medicinal properties of
      volatile Perilla extracts might arise from interactions with the lipid bilayer
      component of biological membranes.

PMID- 21070036
TI  - Chemistry of 2-nitroglycals: a one-pot three-component stereoselective approach
      toward 2-C-branched O-galactosides.
AB  - A convenient one-pot three-component approach for the synthesis of 2-C-branched O
      glycosides has been developed from 2-nitroglycals. These 2-C-branched sugars have
      been shown to be precursors for a variety of biologically and synthetically
      relevant molecules.

PMID- 21070037
TI  - Transfer of a disilenyl moiety to aromatic substrates and lateral functional
      group transformation in aryl disilenes.
AB  - The reaction of 1 equiv of the disilenide Tip2Si?Si(Tip)Li (5; Tip = 2,4,6
      (i)Pr3C6H2) with para-substituted phenyl iodides, 4-X-PhI, transfers the
      Tip2Si?Si(Tip) moiety with elimination of lithium iodide to yield the laterally
      functionalized disilenes Tip2Si?Si(Tip)(4-X-Ph) [X = H (6a), F (6b), Cl (6c), Br
      (6d), I (6e)]. The UV-vis absorptions of 6a-d suggest a linear correlation with
      electronic Hammett parameters. In addition, X-ray structural analyses of 6a-d
      verified the theoretically predicted linear dependence of the Si?Si bond length
      and trans-bent angles. The p-bromophenyl-substituted disilene 6d undergoes a
      metal-halogen exchange reaction to give 6f (X = Li), which was trapped with
      Me3SiCl to afford 6g (X = SiMe3). In the case of simple phenyl halides PhX
      without additional functionality, the reaction with 5 proceeded smoothly for X =
      Br, but phenyl chlorides and fluorides did not react at room temperature even
      after one week, hinting at an S(N)2-type aromatic substitution mechanism.
      Reactions of p- and m-diiodobenzene with 5 afford the corresponding phenylene
      bridged tetrasiladienes p-7 and m-7. While red p-7 (lambda(max) = 508 nm)
      exhibits efficient conjugation of the two Si?Si bonds with the phenylene linker,
      the conjugation in yellow m-7 (lambda(max) = 449 nm) is much less effective.
      Electrochemical studies of m-7 and p-7 as well as density functional theory
      calculations and electron paramagnetic resonance studies of their respective
      radical anions provided further support for the notion of conjugation.

PMID- 21070038
TI  - Cross-linked DNA generated by "bis-click" reactions with bis-functional azides:
      site independent ligation of oligonucleotides via nucleobase alkynyl chains.
AB  - Template-free cross-linking of single-stranded DNA bearing octadiynyl side chains
      at the 7-position of 8-aza-7-deazapurine moieties with bisfunctional azides is
      reported employing a Cu(I)-catalyzed azide-alkyne "bis-click" reaction. Bis
      adducts were formed when the bis-azide:oligonucleotide ratio was 1:1;
      monofunctionalization occurred when the ratio was 15:1. Four-stranded DNA
      consisting of two cross-linked duplexes was obtained after hydridization. Cross
      linked duplexes are as stable as individual duplexes when ligation was introduced
      at terminal positions; ligation at a central position led to a slight duplex
      destabilization.

PMID- 21070039
TI  - Exploring chromium(III)-alkyl bond homolysis with CpCr[(ArNCMe)2CH](R) complexes.
AB  - A range of paramagnetic Cr(III) monohydrocarbyl complexes CpCr[(ArNCMe)2CH](R)
      (Ar = ortho-disubstituted aryl; R = primary alkyl, trimethylsilylmethyl, benzyl,
      phenyl, alkenyl, or alkynyl) were synthesized to investigate how varying the
      steric and electronic properties of the R group affected their propensity for Cr
      R bond homolysis. Most complexes were prepared by salt metathesis of known
      CpCr[(ArNCMe)2CH](Cl) compounds in Et2O with commercial RMgCl solutions, although
      more sterically demanding combinations of Ar and R groups necessitated the use of
      halide-free MgR2 reagents and the Cr(III) tosylate or triflate derivatives.
      Alternative synthetic routes to Cr(III)-R species using the previously reported
      Cr(II) compounds CpCr[(ArNCMe)2CH] and sources of R. radicals (e.g., BEt3 and
      air) were also explored. The UV-vis spectra of the CpCr[(ArNCMe)2CH](R) complexes
      possessed two strong bands with maximum absorbances in the ranges 395-436 nm and
      535-582 nm, with the band in the latter range being particularly characteristic
      of the Cr(III)-R compounds. The Cr-CH2R bond lengths as determined by single
      crystal X-ray diffraction were longer than those in the corresponding Cr-CH3
      complexes, typically falling in the range 2.10 to 2.13 A. The Cr(III) benzyl
      compounds displayed longer Cr-CH2Ph distances, while the bond lengths for the
      alkenyl and alkynyl species were substantially shorter. The rate of Cr-R bond
      homolysis at room temperature was determined by monitoring the reaction of
      Cr(III) neopentyl, benzyl, and isobutyl complexes with excess PhSSPh using UV-vis
      spectroscopy. Although the other primary alkyl, phenyl, and alkenyl compounds did
      not undergo appreciable homolysis under these conditions, they were cleanly
      converted to CpCr[(ArNCMe)2CH](SPh) by photolysis.

PMID- 21070041
TI  - Room-temperature synthesis of single-phase anatase TiO2 by aging and its self
      cleaning properties.
AB  - A facile process to synthesize single-phase anatase titanium dioxide
      nanocrystallites at room temperature was presented. The process included a sol
      gel reaction in an aqueous media followed by aging at room temperature. The
      anatase TiO2 was characterized using XRD, TEM and SEM. The cotton fabrics-coated
      by the anatase nanocrystallites possessed significant photocatalytic self
      cleaning properties as demonstrated by their ability to decompose a colorant and
      degrade red wine and coffee stains, which was equivalent to that of prepared by
      heating or hydrothermal methods described previously. The anatase TiO2-coated
      cotton substrate also showed a high UPF rating of 50+, which means excellent UV
      protection to human wearers. The study of the adhesion between the anatase TiO2
      and the cotton substrate showed that even after 20 times of repeated launderings,
      the-coated substrate was still capable of decomposing stains, which indicated its
      photocatalytic power, though this was reduced compared to that before laundering.
      The tensile strength results of the anatase TiO2-coated cotton fabrics indicate
      that the anatase TiO2 will not damage the cotton substrate even after 20 h of
      continuous UV irradiation. The method of preparing single-phase anatase TiO2
      revealed in this study not only eliminates the need for high temperature
      processing, which means energy saving, but also broadens its applications to poor
      acid-resistant and low thermal stability materials such as many of the
      biomaterials and cellulosic materials.

PMID- 21070040
TI  - Fast reactivity of a cyclic nitrone-calix[4]pyrrole conjugate with superoxide
      radical anion: theoretical and experimental studies.
AB  - Nitrone spin traps have been employed as probes for the identification of
      transient radical species in chemical and biological systems using electron
      paramagnetic resonance (EPR) spectroscopy and have exhibited pharmacological
      activity against oxidative-stress-mediated diseases. Since superoxide radical
      anion (O2(*-)) is a major precursor to most reactive oxygen species and
      calix[4]pyrroles have been shown to exhibit high affinity to anions, a cyclic
      nitrone conjugate of calix[4]pyrrole (CalixMPO) was designed, synthesized, and
      characterized. Computational studies at the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d)
      level suggest a pendant-type linkage between the calix[4]pyrrole and the nitrone
      to be the most efficient design for spin trapping of O2(*-), giving exoergic
      reaction enthalpies (DeltaH(298K,aq)) and free energies (DeltaG(298K,aq)) of 
      16.9 and -2.1 kcal/mol, respectively. (1)H NMR study revealed solvent-dependent
      conformational changes in CalixMPO leading to changes in the electronic
      properties of the nitronyl group upon H-bonding with the pyrrole groups as also
      confirmed by calculations. CalixMPO spin trapping of O2(*-) exhibited robust EPR
      spectra. Kinetic analysis of O2(*-) adduct formation and decay in polar aprotic
      solvents using UV-vis stopped-flow and EPR methods gave a larger trapping rate
      constant for CalixMPO and a longer half-life for its O2(*-) adduct compared to
      the commonly used nitrones. The unusually high reactivity of CalixMPO with O2(*-)
      was rationalized to be due to the synergy between the alpha-effect and
      electrostatic effect by the calix[4]pyrrole moiety on O2(*-) and the nitrone,
      respectively. This work demonstrates for the first time the application of an
      anion receptor for the detection of one of the most important radical
      intermediates in biological and chemical systems (i.e., O2(*-)).

PMID- 21070042
TI  - Tissue engineered, guided nerve tube consisting of aligned neural stem cells and
      astrocytes.
AB  - Injury of the nervous system, particularly in the spinal cord, impairs the
      quality of life of the patient by resulting in permanent loss of neurologic
      function. The main limitation in spinal cord regeneration is the lack of
      extracellular matrix to guide nerves for functional recovery of the transected
      nerve tissue. In the present study, a tissue engineered nerve tube was prepared
      by wrapping neural stem cells (NSCs) on aligned fibers using a micropatterned
      film with astrocytes aligned along the microgrooves to support the NSCs.
      Initially the cell behavior on micropatterns and parallel fibers was investigated
      with cytoskeletal and nuclear staining, immunocytochemistry, and proliferation
      assay using the fiber and the film system separately. The results showed that
      both cells, NSCs in undifferentiated and astrocytes in differentiated form, were
      oriented in the direction of the guiding and support elements, the microgrooves,
      and the microfibers. They were able to grow and increase in number on these cell
      carriers. This trend was also maintained after the components were brought
      together in a nerve tube form and testing in coculture. The cells were able to
      survive and maintained their orientation in the 3D tissue engineered construct.
      The guided nerve tissue engineering approach tested in the present study with
      parallel NSCs and support cells in the tubular construct is expected to provide
      an appropriate environment for nerve regeneration in vivo.

PMID- 21070043
TI  - Synthesis and identification of new 4-arylidene curcumin analogues as potential
      anticancer agents targeting nuclear factor-kappaB signaling pathway.
AB  - A series of curcumin analogues including new 4-arylidene curcumin analogues (4
      arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized. Cell growth
      inhibition assays revealed that most 4-arylidene curcumin analogues can
      effectively decrease the growth of a panel of lung cancer cells at submicromolar
      and low micromolar concentrations. High content analysis technology coupled with
      biochemical studies showed that this new class of 4-arylidene curcumin analogues
      exhibits significantly improved NF-kappaB inhibition activity over the parent
      compound curcumin, at least in part by inhibiting IkappaB phosphorylation and
      degradation via IKK blockage; selected 4-arylidene curcumin analogues also
      reduced the tumorigenic potential of cancer cells in a clonogenic assay. 

PMID- 21070044
TI  - PCE oxidation by sodium persulfate in the presence of solids.
AB  - Batch reactor experiments were performed to determine the effects of solids on
      the oxidation of tetracholoroethylene (PCE) by sodium persulfate in aqueous
      solution. Based on the rates of PCE degradation and chloride formation, PCE
      oxidation by heat-activated sodium persulfate at 50  degrees C in the presence of
      solids ranged from no detectable oxidation of PCE to the levels observed in water
      only reactors. Repeated doses of sodium persulfate, undertaken to overcome the
      inherent solids oxidant demand, improved the rate and extent of PCE oxidation in
      reactors containing reference solids; however, no improvement was observed in
      reactors containing field soils. Additionally, no improvements in PCE oxidation
      were observed after pretreating Great Lakes and Appling soils with ca. 15 g/kg of
      sodium persulfate or 30% hydrogen peroxide to remove oxidizable fractions, or
      acetic acid to remove the carbonate fraction. Based on these results, in situ
      treatment of Great Lakes and Appling soils with heat-activated sodium persulfate
      is not anticipated to result in substantial PCE oxidation, while in situ
      treatment of Fort Lewis soils is anticipated to result in PCE oxidation. This
      work demonstrates the need to perform soil-specific contaminant treatability
      tests rather than soil oxidant demand tests when determining oxidant dosage
      requirements.

PMID- 21070045
TI  - Effect of dispersant on asphaltene suspension dynamics: aggregation and
      sedimentation.
AB  - When oil is mixed with light alkanes, asphaltenes can precipitate out of oil
      solutions in a multistep process that involves the formation of nano and
      colloidal scale particles, the aggregation of asphaltene colloids, and their
      eventual sedimentation. Amphiphilic dispersants can greatly affect this process.
      The mechanism of the dispersant action in colloidal asphaltene suspensions in
      heptane has been shown through previous work to be due in part to a reduction in
      the size of the colloidal asphaltene particles with the addition of dispersant.
      However, previous studies of the sedimentation behavior revealed evidence of
      aggregation processes in the colloidal asphaltenes in heptane that has yet to be
      investigated fully. We investigate the effect of dispersants on this aggregation
      behavior through the use of dynamic light scattering, showing that both the
      amount of dispersant and the amount of heptane dilution can slow the onset of
      aggregation in colloidal asphaltene suspensions. An effective dispersant acts by
      suppressing colloidal aggregation in asphaltene suspensions, as shown by light
      scattering, and therefore also slows separation from the bulk, as revealed
      through macroscopic sedimentation experiments.

PMID- 21070046
TI  - The chemical information contained in the EXAFS Debye-Waller factor: covalency in
      iron(III) bis-diketonato complexes.
AB  - A new procedure to extract chemical information from EXAFS spectroscopy beyond
      the classic parameters, such as coordinating atoms, coordination numbers, and
      bond distances, by thorough analysis of the Debye-Waller-like factor is
      presented. In a comparative study of different iron(III) bis-diketonato
      complexes, which are highly relevant for the iron-catalyzed Michael addition
      reaction, the degree of covalency of the Fe-O bond between the iron center and
      the ligand is determined by a combined EXFAS, Raman, and UV/vis spectroscopic
      approach. A detailed description of the methodology is presented, and it will
      demonstrated that the comparative degree of covalency is correlated to the pK(a)
      value of the coordinating diketone. Moreover, it is shown that the distinct
      catalytic activity of the diketones can not be explained by differences of the
      covalency of the iron-ligand Fe-O bond.

PMID- 21070047
TI  - Establishment of structure-conductivity relationship for tris(2,2'-bipyridine)
      ruthenium ionic C(60) salts.
AB  - Three ionic C(60) salts with [Ru(bpy)(3)](m+) (bpy = 2,2'-bipyridine) as cations
      were synthesized. The UV-vis-NIR spectra, XPS spectra, and elemental analysis
      have demonstrated their compositions: [Ru(bpy)(3)](2)(C(60)) (1),
      [Ru(bpy)(3)](C(60)) (2), and [Ru(bpy)(3)](C(60))(2) (3). Single crystals of
      polycrystalline compounds 1 and 2 were obtained as solvates. At room temperature,
      all three salts are semiconducting with the highest four-probe conductivity
      observed for compound 1 at ~10 S m(-1). The electronic conduction mechanisms can
      be described appropriately by an electron hopping model in this immobilized
      polyvalent redox system.

PMID- 21070048
TI  - Mesoporous TiO2 films fabricated using atmospheric pressure dielectric barrier
      discharge jet.
AB  - TiO2 nanoparticles were synthesized by a facile method of dielectric barrier
      discharge jet (DBD jet) for the dye-sensitized solar cell (DSSC) and other
      potential applications. DBD jet is utilized as a method for deposition of TiO2
      nanoparticles with a 9 MUm/min growth rate which is more than *25 faster than
      reported previously. Their performance was compared with cells fabricated using
      commercial TiO2 nanoparticles (P25). The crystallinity and chemical bonding
      states of samples were characterized by XRD and XPS. Photoanodes fabricated by
      the DBD jet method resulted in approximately 50% higher photoconversion
      efficiency than ones prepared from P25 nanoparticles.

PMID- 21070049
TI  - Tri-, tetra- and pentamers of 9,9'-spirobifluorenes through full ortho-linkage:
      high triplet-energy pure hydrocarbon host for blue phosphorescent emitter.
AB  - 4,4'-Dibromo-9,9'-spirobifluorene was first synthesized, and from this
      intermediate, three fully ortho-linked tri-, tetra-, and pentamers of 9,9'
      spirobifluorenes were constructed. The full ortho-linkage impedes the pi
      conjugation of fluorene units, and guarantees their high triplet energies (E(T) =
      2.80 eV). A device with the trimer as the first pure hydrocarbon host material
      for blue phosphor FIrpic shows a maximum current efficiency of 25 cd/A.

PMID- 21070050
TI  - Highly enantioselective and efficient organocatalytic aldol reaction of acetone
      and beta,gamma-unsaturated alpha-keto ester.
AB  - An effective organocatalytic asymmetric aldol reaction of acetone to beta,gamma
      unsaturated alpha-keto ester has been developed. In the presence of 5 mol % of 9
      amino (9-deoxy)-epicinchona alkaloid and 10 mol % of 4-nitrobenzoic acid, the
      aldol adducts containing a chiral tertiary alcohol moiety were obtained in
      excellent yields and enantioselectivities.

PMID- 21070055
TI  - Publications of Michael R. Wasielewski.

PMID- 21070052
TI  - Biography of Michael R. Wasielewski.

PMID- 21070056
TI  - Materials, interfaces, and photon confinement in dye-sensitized solar cells.
AB  - A series of experiments have been carried out to study the effects of materials
      quality, surface and interfacial modification, and photon confinement on standard
      dye-sensitized solar cells. For these studies, both physical and optical
      characterization of the materials has been performed in detail. In addition, DC
      and AC impedance measurements along with kinetic charge-transport modeling of
      experimental results have yielded information on how to systematically optimize
      the cell efficiency. The same kinetic model has been used to interpret the
      results of a series of experiments on interfacial modification studies using
      fluorine etching in combination with TiCl(4) surface treatment. By using
      specially designed photonic crystals to confine the photons in the cells, it is
      shown that the best cell efficiency can be further increased by about 13%.

PMID- 21070057
TI  - Energy transfer from silica core-surfactant shell nanoparticles to hosted
      molecular fluorophores.
AB  - Very monodisperse water-soluble silica core-surfactant shell nanoparticles (SCSS
      NPs) doped with a rhodamine B derivative were prepared using micelles of F127 as
      nanoreactors for the hydrolysis and condensation of the silica precursor
      tetraethoxysilane (TEOS). The functionalization of the rhodamines with a
      triethoxysilane group allowed the covalent binding of the fluorophores to the
      silica core: no leaking of the dye was observed when the NPs were purified either
      by ultrafiltration (UF) or dialysis. The diameter of the core (d(c) = 10 +/- 1
      nm) was determined by TEM and subtracted from the hydrodynamic diameter, measured
      by DLS, (d(H) = 24 nm, PdI = 0.1) to calculate the shell thickness (~7 nm). The
      presence of a single population of NPs with a radius compatible with the one
      measured by DLS after UF was confirmed by AF4-MALS-RI measurements. The
      concentration of the NPs was measured by MALS-RI. This allowed us to determine
      the average number of rhodamine molecules per NP (10). The ability of the NPs to
      host hydrophobic species as cyanines in the SS was confirmed by fluorescence
      anisotropy measurements. Steady-state and time-resolved fluorescence measurements
      allowed us to observe the occurrence of a very efficient Forster resonance energy
      transfer process from the covalently linked rhodamines to the hosted cyanines. In
      particular, the analysis of the TCSPC data and steady-state measurements revealed
      that the adsorption of a single cyanine molecule causes an almost complete
      quenching of the fluorescence of the NP. Thanks to these observations, it was
      possible to easily determine the concentration of the NPs by fluorescence
      titration experiments. Results are in good agreement with the concentration
      values obtained by MALS-RI. Finally, the hosted cyanine molecule could be
      extracted with (+/-)-2-octanol, demonstrating the reversibility of the adsorption
      process.

PMID- 21070058
TI  - Electronic properties and supramolecular organization of terminal
      bis(alkylethynyl)-substituted benzodithiophenes.
AB  - Benzodithiophene (BDT) was symmetrically bisubstituted in the terminal positions
      with five different alkynes C=C-(C(n)H(2n+1)) with n = 4, 6, 8, 10, 12. The
      materials were characterized as potential materials for field-effect transistor
      applications. Electrochemical measurements in solution and photophysical
      measurements in solution and in the solid state, together with UV photoelectron
      spectroscopy in air and quantum-chemical calculations, elucidate the nature of
      the frontier orbitals and of the excited states as well as their deactivation
      pathways. Structural information on the molecular assembly in the solid state,
      both at room temperature and at elevated temperatures, is obtained by a
      combination of DSC, polarized optical microscopy, and 2D-WAXS, which point to the
      crystallinity of the compounds in all phases and reveal pi-stacking arrangements
      independently of the length of the alkyl side chains.

PMID- 21070059
TI  - Reduced electronic spaces for modeling donor/acceptor interactions.
AB  - Diabatic states for donor (D) and acceptor (A) interactions in electron transfer
      (ET) processes are formulated and evaluated, along with coupling elements (H(DA))
      and effective D/A separation distances (r(DA)), for reduced electronic spaces of
      variable size, using the generalized Mulliken Hush model (GMH), applicable to an
      arbitrary state space and nuclear configuration, and encompassing Robin-Day class
      III and as well as class II situations. Once the electronic state space is
      selected (a set of n >= 2 adiabatic states approximated by an orbital space based
      on an effective 1-electron (1-e) Hamiltonian), the charge-localized GMH diabatic
      states are obtained as the eigenstates of the dipole moment operator, with
      rotations to yield locally adiabatic states for sites with multiple states. The 1
      e states and energies are expressed in terms of Kohn-Sham orbitals and orbital
      energies. Addressing questions as to whether the estimate of H(DA) "improves" as
      one increases n, and in what sense the GMH approach "converges" with n, we carry
      out calculations for three mixed-valence binuclear Ru complexes, from which we
      conclude that the 2-state (2-st) model gives the most appropriate estimate of the
      effective coupling, similar (to within a rms deviation of <=15%) to coupling
      elements obtained by superexchange correction of H(DA) values based on larger
      spaces (n = 3-6), and thus yielding a quasi-invariant value for H(DA) over the
      range explored in the calculations (n = 2-6). An analysis of the coupling and
      associated D and A states shows that the 2-st coupling involves crucial mixing
      with intervening bridge states (D and A "tails"), while increasingly larger state
      spaces for the same system yield increasingly more localized D and A states (and
      weaker coupling), with H(DA) tending to approach the limit of "bare" or "through
      space" coupling. These results help to reconcile seemingly contradictory
      assertions in the recent literature regarding the proper role of multistate
      frameworks in the formulation of coupling for both intra- and intermolecular ET
      systems.The present results are compared in detail with other reported results.

PMID- 21070060
TI  - Ultrafast electron transfer dynamics in ruthenium polypyridyl complexes with a pi
      conjugated ligand.
AB  - The excited-state dynamics of two mixed-ligand mononuclear ruthenium(II)
      complexes, [(bpy)(2)RuL(DQ)](4+) (where bpy = 2,2'-bipyridine, L(DQ) = 1-[4-(4'
      methyl)-2,2'-bipyridyl)]-2-[4-(4'-N,N'-tetramethylene-2,2'-bipyridinium]) and
      [(bpy)(2)RuL](2+) (where L = 1, 2-bis[4-(4'-methyl)-2,2'-bipyridyl)]ethene), were
      investigated by femtosecond transient absorption spectroscopy. Photoexcitation of
      the [(bpy)(2)RuL(DQ)](4+) complex at three separate pump wavelengths leads to a
      common charge-separated state consisting of Ru(3+) and an excited electron
      delocalized over the extended pi-system centered on the ethenyl moiety of the
      L(DQ) ligand. In [(bpy)(2)RuL](2+), the excited electron is unable to delocalize
      throughout the pi system and remains on the bipyridyl end of ligand L closest to
      the ruthenium atom. Vibrational cooling in the charge-separated state of
      [(bpy)(2)RuL(DQ)](4+) indicates that this state is formed faster than excess
      energy can be dispersed to the solvent and orders of magnitude more rapidly than
      in previously studied ruthenium-diquat or ruthenium-viologen dyads with
      nonconjugated linkers.

PMID- 21070061
TI  - Azomethane: nonadiabatic photodynamical simulations in solution.
AB  - The nonadiabatic deactivation of trans-azomethane starting from the npi* state
      has been investigated in gas phase, water, and n-hexane using an on-the-fly
      surface-hopping method. A quantum mechanical/molecular mechanics (QM/MM) approach
      was used employing a flexible quantum chemical level for the description of
      electronically excited states and bond dissociation (generalized valence bond
      perfect-pairing complete active space). The solvent effect on the lifetime and
      structural parameters of azomethane was investigated in detail. The calculations
      show that the nonadiabatic deactivation is characterized by a CNNC torsion,
      mainly impeded by mechanic interaction with the solvent molecules. The similar
      characteristics of the dynamics in polar and nonpolar solvent indicate that
      solvent effects based on electrostatic interactions do not play a major role.
      Lifetimes increase by about 20 fs for both solvents with respect to the 113 fs
      found for the gas phase. The present subpicosecond dynamics also nicely show an
      example of the suppression of C-N dissociation by the solvent cage.

PMID- 21070062
TI  - Simulations of photopumping in doubly illuminated liquid membranes containing
      photoactive carriers.
AB  - A steady-state model used to simulate photofacilitated active transport against a
      concentration gradient, called photopumping, is described. Central to this model
      is the idea that the carrier can be in either a strongly binding or a weakly
      binding form and light can be used to control the interconversion rate between
      the two forms. Most experimental and theoretical studies have focused on systems
      in which only one side of the membrane is illuminated at a time to form singly
      illuminated liquid membranes. This study explores membranes in which both the
      feed and the sweep side are illuminated simultaneously with light of different
      wavelengths to form doubly illuminated liquid membranes. Doubly illuminated
      liquid membranes can sustain transport against concentration gradients in which
      the solute concentration in the sweep is a factor of 10 or more higher than that
      in the feed, while transport in singly illuminated liquid membranes falls off at
      lower concentration gradients. In addition, carrier properties that are important
      in single illumination such as the interconversion rates between the weakly and
      the strongly binding forms of the carrier are not important for doubly
      illuminated membranes, meaning that the range of suitable carriers will be much
      greater for double illumination than for single illumination.

PMID- 21070063
TI  - Influence of the O3 protecting group on stereoselectivity in the preparation of C
      mannopyranosides with 4,6-O-benzylidene protected donors.
AB  - alpha-C-Glucopyranosides and mannopyranosides are obtained in 65-85% yields from
      4,6-O-benzylidene-protected glucosyl and mannosyl thioglycosides bearing ester
      functionality at the 3-O-position by a coupling reaction with C-nucleophiles on
      activation with diphenyl sulfoxide, 2,4,6-tri-tert-butylpyrimidine, and
      trifluoromethanesulfonic anhydride.

PMID- 21070064
TI  - Redox and electrocatalytic properties of mimochrome VI, a synthetic heme peptide
      adsorbed on gold.
AB  - Mimochrome VI (MC-VI) is a synthetic heme peptide containing a helix-heme-helix
      sandwich motif designed to reproduce the catalytic activity of heme oxidases. The
      thermodynamics of Fe(III) to Fe(II) reduction and the kinetics of the electron
      transfer process for MC-VI immobilized through hydrophobic interactions on a gold
      electrode coated with a nonpolar SAM of decane-1-thiol have been determined
      through cyclic voltammetry. Immobilization slightly affects the reduction
      potential of MC-VI, which under these conditions electrocatalytically turns over
      molecular oxygen. This work sets the premise for the exploitation of totally
      synthetic mimochrome-modified electrode surfaces for clinical and pharmaceutical
      biosensing.

PMID- 21070065
TI  - Highly enantioselective organocatalytic alpha-amination reactions of aryl
      oxindoles: developing designer multifunctional alkaloid catalysts.
AB  - An enantioselective alpha-amination of aryl oxindoles catalyzed by a dimeric
      quinidine has been developed. The reaction is general, broad in substrate scope,
      and affords the desired products in good yields with good to excellent
      enantioselectivities. This study provides the first examples of a general
      organocatalytic method for the creation of nitrogen-containing, tetrasubstituted
      chiral centers at C(3) of various aryl oxindoles. Furthermore, new catalysts and
      insights into structural elements of the catalysts that significantly influence
      enantioselectivities are disclosed.

PMID- 21070066
TI  - Quantum chemical and molecular dynamics study of the coordination of Th(IV) in
      aqueous solvent.
AB  - In this work, we investigate the solvation of tetravalent thorium Th(IV) in
      aqueous solution using classical molecular dynamics simulations at the 10 ns
      scale and based on polarizable force-field approaches, which treat explicitly the
      covalent character of the metal-water interaction (and its inherent cooperative
      character). We have carried out a thorough analysis of the accuracy of the ab
      initio data that we used to adjust the force-field parameters. In particular, we
      show that large atomic basis sets combined with wave function-based methods (such
      as the MP2 level) have to be preferred to density functional theory when
      investigating Th(IV)/water aggregates in gas phase. The information extracted
      from trajectories in solution shows a well-structured Th(IV) first hydration
      shell formed of 8.25 +/- 0.2 water molecules and located at about 2.45 +/- 0.02 A
      and a second shell of 17.5 +/- 0.5 water molecules at about 4.75 A. Concerning
      the first hydration sphere, our results correspond to the lower bounds of
      experimental estimates (which range from 8 to 12.7); however, they are in very
      good agreement with the average of existing experimental data, 2.45 +/- 0.02 A.
      All our results demonstrate the predictable character of the proposed approach,
      as well as the need of accounting explicitly for the cooperative character of
      charge-transfer phenomena affecting the Th(IV)/water interaction to build up
      reliable and accurate force-field approaches devoted to such studies.

PMID- 21070067
TI  - Amide vibrations and their conformational dependences in beta-peptide.
AB  - The characteristics of the amide-A and amide-I modes in a beta-homoalanine
      dipeptide (beta-HADP) have been examined as a function of backbone dihedral
      angles. The harmonic frequencies were obtained using the density functional
      theory. The anharmonic frequencies and diagonal anharmonicities were obtained by
      using the Morse potential. Local-mode frequencies and intermode couplings were
      obtained using the computed normal-mode frequencies and eigenvectors. It was
      found that the vibrational frequencies for the two types of amide modes are both
      conformational-dependent. The inter-amide-A and inter-amide-I couplings in the
      beta-peptides were predicted to be generally weaker than those in the alpha
      peptides. Structural bases of the amide-A and amide-I local modes in the beta
      peptides are discussed.

PMID- 21070068
TI  - Identification of potentially involved proteins in levofloxacin resistance
      mechanisms in Coxiella burnetii.
AB  - The etiological agent of Q fever, Coxiella burnetii, is an obligate intracellular
      bacterium that multiplies within a phagosome-like parasitophorous vacuole.
      Fluoroquinolones have been used as an alternative therapy for Q fever. Resistance
      to fluoroquinolones can arise via several mechanisms utilized by pathogens to
      avoid killing. Until today, genome-based studies have shown that the main
      mechanism of C. burnetii to resist inhibition by fluoroquinolones is based on
      mutations in quinolone-resistance-determining region (QRDR). In this study, in a
      broader search at the protein level for C. burnetii mechanisms that confer
      resistance to fluoroquinolones, the proteomes of in vitro developed
      fluoroquinolone resistant bacteria and susceptible bacteria were compared using
      the MS-driven combined fractional diagonal chromatography (COFRADIC) proteomics
      technique. Quantitative comparison of the 381 proteins identified in both strains
      indicated the different expression of 15 bacterial proteins. These proteins are
      involved in different cellular processes indicating that the antibiotic
      resistance mechanism of the bacterium is a multifaceted process.

PMID- 21070069
TI  - Polypharmacology directed compound data mining: identification of promiscuous
      chemotypes with different activity profiles and comparison to approved drugs.
AB  - Increasing evidence that many pharmaceutically relevant compounds elicit their
      effects through binding to multiple targets, so-called polypharmacology, is
      beginning to change conventional drug discovery and design strategies. In light
      of this paradigm shift, we have mined publicly available compound and bioactivity
      data for promiscuous chemotypes. For this purpose, a hierarchy of active
      compounds, atomic property based scaffolds, and unique molecular topologies were
      generated, and activity annotations were analyzed using this framework. Starting
      from ~35 000 compounds active against human targets with at least 1 MUM potency,
      33 chemotypes with distinct topology were identified that represented molecules
      active against at least 3 different target families. Network representations were
      utilized to study scaffold-target family relationships and activity profiles of
      scaffolds corresponding to promiscuous chemotypes. A subset of promiscuous
      chemotypes displayed a significant enrichment in drugs over bioactive compounds.
      A total of 190 drugs were identified that had on average only 2 known target
      annotations but belonged to the 7 most promiscuous chemotypes that were active
      against 8-15 target families. These drugs should be attractive candidates for
      polypharmacological profiling.

PMID- 21070070
TI  - Depletion of long-acting ampicillin in goat milk following intramuscular
      administration.
AB  - Although goat milk production represents today a very small percentage of the
      world milk market, this percentage has been growing continuously during the past
      20 years. Goat milk is the basic milk supply in many developing countries and
      provides tasteful derivative products in developed countries. Goats, as well as
      all milk-producing animals, can be affected by mastitis, but goats being
      considered a minor species, few drugs are specifically registered for these
      animals; most, at least for mastitis treatment, are usually tested and registered
      for use in cows. This situation leads often to the adoption for goat milk of
      withdrawal periods defined for cows even if these extrapolations prove almost
      never valid for goats. In the present study, the elimination of the beta-lactam
      antibacterial agent ampicillin in goat milk was investigated. Ampicillin was
      chosen because it is one of the most common antibiotics used by goat farmers
      against mastitis due to the fact that it is well tolerated and has short
      elimination times in cows. Goats were treated with long-acting ampicillin at 15
      mg (kg of body weight)(-1) by double intramuscular injection at 72 h interval.
      Milk was collected in a 12 h milking scheme. The method used to determine the
      levels of ampicillin in goat milk was based on a liquid-liquid extraction of this
      drug from the matrix, successive derivatization with formaldehyde, and final
      separation by HPLC with fluorescence detection. The results point out a slow
      depletion of ampicillin and, consequently, a withdrawal period (13 milkings)
      longer than that extrapolated and authorized for cows and sheep. 

PMID- 21070071
TI  - Ursolic acid induces allograft inflammatory factor-1 expression via a nitric
      oxide-related mechanism and increases neovascularization.
AB  - Ursolic acid (UA), a triterpenoid compound found in plants, is used in the human
      diet and in medicinal herbs and possesses a wide range of biological benefits
      including antioxidative, anti-inflammatory, and anticarcinogenic effects.
      Endothelial expression of allograft inflammatory factor-1 (AIF-1) mediates
      vasculogenesis, and nitric oxide (NO) produced by endothelial NO (eNOS)
      represents a mechanism of vascular protection. It is unclear whether UA affects
      the neovascularization mediated by AIF-1 and eNOS expression. This study
      investigated the effects and mechanisms of UA on angiogenesis in vivo in hind
      limb ischemic animal models and in vitro in human coronary artery endothelial
      cells (HCECs). This study explored the impact of UA on endothelial cell (EC)
      activities in vitro in HCECs, vascular neovasculogenesis in vivo in a mouse hind
      limb ischemia model, and the possible role of AIF-1 in vasculogenesis. The
      results demonstrate that UA enhances collateral blood flow recovery through
      induction of neovascularization in a hind limb ischemia mouse model. In vitro
      data showed that UA increases tube formation and migration capacities in human
      endothelial cells, and exposing HCECs to UA increased AIF-1 expression through a
      NO-related mechanism. Moreover, UA administration increased capillary density and
      eNOS and AIF-1 expression in ischemic muscle. These findings suggest that UA may
      be a potential therapeutic agent in the induction of neovascularization and
      provide a novel mechanistic insight into the potential effects of UA on ischemic
      vascular diseases.

PMID- 21070072
TI  - Effects of refining and removal of persistent organic pollutants by short-path
      distillation on nutritional quality and oxidative stability of fish oil.
AB  - Food and feed legislations are implemented to control the level of unwanted
      persistent organic pollutants (POPs) below health risk concerns. Short-path
      distillation is established as the most effective industrial process to remove
      POPs in fish oil. However, the technology involves heating of the oil to high
      temperature levels (>200  degrees C) that possibly give unwanted heat-induced
      side reactions and coevaporation of minor compounds of importance for the
      nutritional quality of the oil. The effects on retention of vitamins,
      cholesterol, and unsaponifiable compounds, geometrical isomerization, loss of
      polyunsaturated fatty acids (PUFA), oxidation level, and oxidative stability have
      been studied on the basis of experiments designed to optimize and model the
      effect of process conditions (i.e., evaporator temperature, feed rate, and
      addition of working fluid) on the reduction of POPs. Loss of volatile nutrients
      was observed, but the extent will depend on the process conditions needed to
      obtain target decontamination level, as well as the concentration ratio and
      difference in vapor pressure between free and esterified forms of the studied
      compounds. Some reduction in oxidation level was documented with preservation of
      PUFA level and quality. Oxidative stability was influenced both positively and
      negatively depending on the applied process conditions. Generally, no adverse
      negative effects on the nutritional quality of the fish oil could be documented.
      Optimal process conditions were modeled that ensure removal of POPs to within
      legislation levels while retaining most of the vitamin levels in fish oil. A 76%
      reduction of the WHO-PCDD/F-PCB-TEQ level in the used feedstock was needed to be
      in accordance with the voluntary industrial monograph of GOED. This could be
      achieved on the basis of operation conditions giving <20% loss of vitamins. A 90%
      decontamination rate gave vitamin retentions in the 60-90% range. 

PMID- 21070073
TI  - Biologically inspired highly durable iron phthalocyanine catalysts for oxygen
      reduction reaction in polymer electrolyte membrane fuel cells.
AB  - In the present work, we have designed and synthesized a new highly durable iron
      phtalocyanine based nonprecious oxygen reduction reaction (ORR) catalyst (Fe-SPc)
      for polymer electrolyte membrane fuel cells (PEMFCs). The Fe-SPc, with a novel
      structure inspired by that of naturally occurring oxygen activation catalysts, is
      prepared by a nonpyrolyzing method, allowing adequate control of the atomic
      structure and surface properties of the material. Significantly improved ORR
      stability of the Fe-SPc is observed compared with the commercial Fe-Pc catalysts.
      The Fe-SPc has similar activity to that of the commercial Fe-Pc initially, while
      the Fe-SPc displays 4.6 times higher current density than that of the commercial
      Fe-Pc after 10 sweep potential cycles, and a current density that is 7.4 times
      higher after 100 cycles. This has been attributed to the incorporation of
      electron-donating functional groups, along with a high degree of steric hindrance
      maintaining active site isolation. Nonprecious Fe-SPc is promising as a potential
      alternative ORR electrocatalyst for PEMFCs.

PMID- 21070074
TI  - Proteomic response to sublethal cadmium exposure in a sentinel fish species,
      Cottus gobio.
AB  - The present study aimed at evaluating the toxicity of short-term cadmium (Cd)
      exposure in the European bullhead Cottus gobio, a candidate sentinel species.
      Several enzymatic activity assays (citrate synthase, cytochrome c oxidase, and
      lactate dehydrogenase) were carried out in liver and gills of fish exposed to
      0.01, 0.05, 0.25, and 1 mg Cd/L for 4 days. Exposure to high Cd concentrations
      significantly altered the activity of these enzymes either in liver and/or in
      gills. Second, 2D-DIGE technique was used to identify proteins differentially
      expressed in tissues of fish exposed to either 0.01 or 1 mg Cd/L. Fifty-four
      hepatic protein spots and 37 branchial protein spots displayed significant
      changes in abundance in response to Cd exposure. A total of 26 and 12 different
      proteins were identified using nano LC-MS/MS in liver and gills, respectively.
      The identified differentially expressed proteins can be categorized into diverse
      functional classes, related to metabolic process, general stress response,
      protein fate, and cell structure for instance. This work provides new insights
      into the biochemical and molecular events in Cd-induced toxicity in fish and
      suggests that further studies on the identified proteins could provide crucial
      information to better understand the mechanisms of Cd toxicity in fish.

PMID- 21070075
TI  - CyberKnife(R) robotic stereotactic radiosurgery and stereotactic body radiation
      therapy.

PMID- 21070076
TI  - CyberKnife stereotactic radiosurgery for intracranial neoplasms, with a focus on
      malignant tumors.
AB  - Stereotactic radiosurgery is well established as a means of managing intracranial
      tumors, both as an adjuvant to surgical resection, and also as a primary
      treatment modality for those tumors that are considered unresectable by
      conventional surgical means. Of particular concern during radiosurgery of brain
      tumors is the risk of radiation damage to otherwise healthy tissue, potentially
      resulting in cognitive impairment. The conformality and precise targeting of the
      CyberKnife radiation beam enables this risk to be minimized to a greater extent
      than hitherto possible, which may allow treatment to be completed in a small
      number of fractions, thereby improving the quality of life for patients. The
      CyberKnife has proven particularly valuable in the treatment of metastases, which
      represent the great majority of brain tumors, though its role in the management
      of malignant glial tumors remains a subject of controversy. This article reviews
      the published studies on the efficacy of CyberKnife radiosurgery for brain tumors
      of both glial and metastatic origin, and considers its future role in the
      management of such lesions.

PMID- 21070077
TI  - Targeting accuracy in real-time tumor tracking via external surrogates: a
      comparative study.
AB  - The use of external surrogates to predict tumor motion in real-time for extra
      cranial sites requires the use of accurate correlation models. This is extremely
      challenging when motion prediction is to be performed over several breathing
      cycles, as occurs for real-time tumor tracking with Cyberknife((R))
      Synchrony((R)). In this work we compare three different approaches to infer tumor
      motion based on external surrogates, since no comparative study is available to
      assess the accuracy of correlation models in tumor tracking over a long time
      period. We selected 20 cases in a database of 130 patients treated with real-time
      tumor tracking by means of the Synchrony((R)) module. The implemented correlation
      models comprise linear/quadratic correlation, artificial neural networks and
      fuzzy logic. The accuracy of each correlation model is evaluated on the basis of
      ground truth tumor position information acquired during treatment, as detected by
      means of stereoscopic X-ray imaging. Results show that the implemented models
      achieve an error reduction with respect to Synchrony((R)), measured at the 95%
      confidence level, up to 10.8% for the fuzzy logic approach. This latter is able
      to partly reduce the incidence of tumor tracking errors above 6 mm, resulting in
      improved accuracy for larger discrepancies. In conclusion, complex models are
      suggested to predict tumor motion over long time periods. This leads to an
      effective improvement with respect to Cyberknife((R)) Synchrony((R)). Future
      studies will investigate the sensitivity of the implemented models to the input
      database, in order to define optimal strategies.

PMID- 21070078
TI  - Apparatus-dependent dosimetric differences in spine stereotactic body
      radiotherapy.
AB  - The purpose of this investigation was to study apparatus-dependent dose
      distribution differences specific to spine stereotactic body radiotherapy (SBRT)
      treatment planning. This multi-institutional study was performed evaluating an
      image-guided robotic radiosurgery system (CK), intensity modulated protons (IMP),
      multileaf collimator (MLC) fixed-field IMRT with 5 mm (11 field), 4 mm (9 field),
      and 2.5 mm (8- and 9-field) leaf widths and intensity modulated volumetric arc
      therapy (IMVAT) with a 2.5 mm MLC. Treatment plans were systematically developed
      for targets consisting of one, two and three consecutive thoracic vertebral
      bodies (VBs) with the esophagus and spinal cord contoured as the organs at risk.
      It was found that all modalities achieved acceptable treatment planning
      constraints. However, following normalization fixed field IMRT with a 2.5 mm MLC,
      IMVAT and IMP systems yielded the smallest ratio of maximum dose divided by the
      prescription dose (MD/PD) for one-, two- and three-VB PTVs (ranging from 1.1
      1.16). The 2.5 mm MLC 9-field IMRT, IMVAT and CK plans resulted in the least dose
      to 0.1 cc volumes of spinal cord and esophagus. CK plans had the greatest degree
      of target dose inhomogeneity. As the level of complexity increased with an
      increasing number of vertebral bodies, distinct apparatus features such as the
      use of a high number of beams and a finer leaf size MLC were favored. Our study
      quantified apparatus-dependent dose-distribution differences specific to spine
      SBRT given strict, but realistic, constraints and highlights the need to
      benchmark physical dose distributions for multi-institutional clinical trials.

PMID- 21070079
TI  - Stereotactic body radiotherapy as boost for organ-confined prostate cancer.
AB  - Stereotactic body radiotherapy (SBRT) boost following external beam radiation
      therapy (EBRT) for advanced localized prostate cancer may reduce toxicity while
      escalating the dose. We present preliminary biochemical control and urinary,
      rectal and sexual toxicities for 73 patients treated with SBRT as a boost to
      EBRT. Forty-one intermediate- and 32 high-risk localized prostate cancer patients
      received 45 Gy EBRT with SBRT boost. Twenty-eight patients (38.3%) received a
      total SBRT boost dose of 18 Gy (3 fractions of 6 Gy), 28 patients (38.3%)
      received 19.5 Gy (3 fractions of 6.5 Gy), and 17 patients (23.2%) received 21 Gy
      (3 fractions of 7 Gy). Toxicity was assessed using the Radiation Therapy Oncology
      Group urinary and rectal toxicity scale. Biochemical failure was assessed using
      the Phoenix definition. The median follow-up was 33 months (range, 22 - 43
      months). Less than 7% Grade II and no higher grade acute toxicities occurred. To
      date, one Grade III and no Grade IV late toxicities occurred. For the 97% of
      patients with 24 months minimum follow-up, 71.8% achieved a PSA nadir threshold
      of 0.5 ng/mL. Three intermediate-risk and seven high-risk biochemical failures
      occurred; one high-risk patient died of his cancer. Three-year actuarial
      biochemical control rates were 89.5% and 77.7% for intermediate- and high-risk
      patients, respectively. SBRT boost for prostate cancer treatment is safe and
      feasible with minimal acute toxicity. At 33 months late toxicity and biochemical
      control are promising. Long-term durability of these findings remains to be
      established.

PMID- 21070080
TI  - Histopathologic effects of hypofractionated robotic radiation therapy on
      malignant and benign prostate tissue.
AB  - We describe the first histopathologic analysis of prostatic tissue following
      hypofractionated robotic radiation therapy. A 66 year-old man presented with
      stage II, low risk adenocarcinoma of the prostate and underwent elective
      conformal hypofractionated radiation therapy. His pretreatment evaluation
      revealed T1c adenocarcinoma, Gleason's grade 3 + 3 = 6 and a prostate specific
      antigen (PSA) level of 4.87 ng/ml. Hypofractionated radiation therapy (37.5 Gy in
      five daily fractions of 7.5 Gy) was completed on an Internal Review Board
      approved protocol. One year later, he developed progressive urinary retention.
      Transurethral prostatic resection was performed to alleviate obstructive
      symptoms. Bilobar hypertrophy was observed without evidence of stricture.
      Histolopathologic analyses of resected prostate tissues revealed changes
      consistent with radiation treatment, including cellular changes, inflammation,
      glandular atrophy and hyperplasia. There was no evidence of residual cancer,
      fibrosis or necrosis. The patient's postoperative course was uneventful with post
      treatment PSA of 0.5 ng/ml and residual grade 1 stress incontinence.

PMID- 21070081
TI  - CyberKnife stereotactic ablative radiotherapy for lung tumors.
AB  - Stereotactic ablative radiotherapy (SABR) has emerged as a promising treatment
      for early stage non-small cell lung cancer, particularly for patients unable to
      tolerate surgical resection. High rates of local tumor control have been
      demonstrated with acceptable toxicity and the practical advantage of a short
      course of treatment. The CyberKnife image-guided robotic radiosurgery system has
      unique technical characteristics that make it well suited for SABR of tumors that
      move with breathing, including lung tumors. We review the qualities of the
      CyberKnife platform for lung tumor SABR, and provide a summary of clinical data
      using this system specifically.

PMID- 21070082
TI  - Tumor bed radiosurgery following resection of brain metastases: a review.
AB  - There is a growing interest in adjuvant radiosurgery following resection of
      hematogenous brain metastases. We have identified 12 series reporting on a total
      of 480 patients treated to a tumor bed following microsurgery. These cases fall
      into 3 paradigms: adjuvant radiosurgery as an alternative to whole-brain
      radiotherapy (WBRT), radiosurgery as an intensification of adjuvant WBRT and
      adjuvant radiosurgery for patients having failed prior WBRT. For these paradigms
      the reported crude local control rates are 79%, 92% and 95%, respectively. The
      procedure appears well tolerate with approximately a 5% risk of late radiation
      necrosis. Prospective data is lagging behind clinical practice and plans for
      prospective trials are discussed.

PMID- 21070083
TI  - Clinical results of a pilot study on stereovision-guided stereotactic
      radiotherapy and intensity modulated radiotherapy.
AB  - Real-time stereovision-guidance has been introduced for efficient and convenient
      fractionated stereotactic radiotherapy (FSR) and image-guided intensity-modulated
      radiation therapy (IMRT). This first pilot study is to clinically evaluate its
      accuracy and precision as well as impact on treatment doses. Sixty-one FSR
      patients wearing stereotactic masks (SMs) and nine IMRT patients wearing flexible
      masks (FMs), were accrued. Daily target reposition was initially based-on biplane
      radiographs and then adjusted in six degrees of freedom under real-time
      stereovision guidance. Mean and standard deviation of the head displacements
      measured the accuracy and precision. Head positions during beam-on times were
      measured with real-time stereovisions and used for determination of delivered
      doses. Accuracy +/- +/- precision in direction with the largest errors shows
      improvement from 0.4 +/- 2.3 mm to 0.0 +/- 1.0 mm in the inferior-to-superior
      direction for patients wearing SM or from 0.8 +/- 4.3 mm to 0.4 +/- 1.7 mm in the
      posterior-to-anterior direction for patients wearing FM. The image-guidance
      increases target volume coverage by >30% for small lesions. Over half of head
      position errors could be removed from the stereovision-guidance. Importantly, the
      technique allows us to check head position during beam-on time and makes it
      possible for having frameless head refixation without tight masks.

PMID- 21070084
TI  - Hypofractionated stereotactic body radiotherapy for primary and metastatic liver
      tumors using the novalis image-guided system: preliminary results regarding
      efficacy and toxicity.
AB  - www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity
      of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors
      using the Novalis image-guided radiotherapy system. After preliminarily treating
      liver tumors using the Novalis system from July 2006, we started a protocol-based
      study in February 2008. Eighteen patients (6 with primary hepatocellular
      carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy,
      depending upon their planned dose distribution and liver function, delivered in
      10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were
      used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh
      classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged
      from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the
      Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced
      liver disease (RILD) was defined by Lawrence's criterion. The median follow-up
      period was 14.5 months. For all patients, the 1-year overall survival and local
      control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was
      observed in 5 patients, but no RILD or chronic liver dysfunction was observed.
      SBRT using the Novalis image-guided system is safe and effective for treating
      primary and metastatic liver tumors. Further investigation of SBRT for liver
      tumors is warranted. In view of the acceptable toxicity observed with this
      protocol, we have moved to a new protocol to shorten the overall treatment time
      and escalate the dose.

PMID- 21070085
TI  - Toward truly optimal IMRT dose distribution: inverse planning with voxel-specific
      penalty.
AB  - PURPOSE: To establish an inverse planning framework with adjustable voxel penalty
      for more conformal IMRT dose distribution as well as improved interactive
      controllability over the regional dose distribution of the resultant plan.
      MATERIALS AND METHOD: In the proposed coarse-to-fine planning scheme, a
      conventional inverse planning with organ specific parameters is first performed.
      The voxel penalty scheme is then "switched on" by allowing the prescription dose
      to change on an individual voxel scale according to the deviation of the actual
      voxel dose from the ideally desired dose. The rationale here is intuitive: when
      the dose at a voxel does not meet its ideal dose, it simply implies that this
      voxel is not competitive enough when compared with the ones that have met their
      planning goal. In this case, increasing the penalty of the voxel by varying the
      prescription can boost its competitiveness and thus improve its dose. After the
      prescription adjustment, the plan is re-optimized. The dose adjustment/re
      optimization procedure is repeated until the resultant dose distribution cannot
      be improved anymore. The prescription adjustment on a finer scale can be
      accomplished either automatically or manually. In the latter case, the
      regions/voxels where a dose improvement is needed are selected visually, unlike
      in the automatic case where the selection is done purely based on the difference
      of the actual dose at a given voxel and its ideal prescription. The performance
      of the proposed method is evaluated using a head and neck and a prostate case.
      RESULTS: An inverse planning framework with the voxel-specific penalty is
      established. By adjusting voxel prescriptions iteratively to boost the region
      where large mismatch between the actual calculated and desired doses occurs,
      substantial improvements can be achieved in the final dose distribution. The
      proposed method is applied to a head and neck case and a prostate case. For the
      former case, a significant reduction in the maximum dose to the brainstem is
      achieved while the PTV dose coverage is greatly improved. The doses to other
      organs at risk are also reduced, ranging from 10% to 30%. For the prostate case,
      the use of the voxel penalty scheme also results in vast improvements to the
      final dose distribution. The PTV experiences improved dose uniformity and the
      mean dose to the rectum and bladder is reduced by as much as 15%. CONCLUSION:
      Introduction of the spatially non-uniform and adjustable prescription provides
      room for further improvements of currently achievable dose distributions and
      equips the planner with an effective tool to modify IMRT dose distributions
      interactively. The technique is easily implementable in any existing inverse
      planning platform, which should facilitate clinical IMRT planning process and, in
      future, off-line/on-line adaptive IMRT.

PMID- 21070086
TI  - Low-dose photon and simulated solar particle event proton effects on Foxp3+ T
      regulatory cells and other leukocytes.
AB  - Radiation is a major factor in the spaceflight environment that has carcinogenic
      potential. Astronauts on missions are continuously exposed to low-dose/low-dose
      rate (LDR) radiation and may receive relatively high doses during a solar
      particle event (SPE) that consists primarily of protons. However, there are very
      few reports in which LDR photons were combined with protons. In this study,
      C57BL/6 mice were exposed to 1.7 Gy simulated SPE (sSPE) protons over 36 h, both
      with and without pre-exposure to 0.01 Gray (Gy) LDR g-rays at 0.018 cGy/h.
      Apoptosis in skin samples was determined by immunohistochemistry immediately post
      irradiation (day 0). Spleen mass relative to body mass, white blood cells (WBC),
      major leukocyte populations, lymphocyte subsets (T, Th, Tc, B, NK), and
      CD4(+)CD25(+)Foxp3+ T regulatory (Treg) cells were analyzed on days 4 and 21.
      Apoptosis in skin samples was evident in all irradiated groups; the LDR+sSPE mice
      had the greatest expression of activated caspase-3. On day 4 post-irradiation,
      the sSPE and LDR+sSPE groups had significantly lower WBC counts in blood and
      spleen compared to non-irradiated controls (p < 0.05 vs. 0 Gy).
      CD4(+)CD25(+)Foxp3(+) Treg cell numbers in spleen were decreased at day 4, but
      proportions were increased in the sSPE and LDR+sSPE groups (p < 0.05 vs. 0 Gy).
      By day 21, lymphocyte counts were still low in blood from the LDR+sSPE mice,
      especially due to reductions in B, NK, and CD8(+) T cytotoxic cells. The data
      demonstrate, for the first time, that pre-exposure to LDR photons did not protect
      against the adverse effects of radiation mimicking a large solar storm. The
      increased proportion of immunosuppressive CD4+CD25(+) Foxp3(+) Treg and
      persistent reduction in circulating lymphocytes may adversely impact immune
      defenses that include removal of sub-lethally damaged cells with carcinogenic
      potential, at least for a period of time post-irradiation.

PMID- 21070087
TI  - Culture at the centre of community based aged care in a remote Australian
      Indigenous setting: a case study of the development of Yuendumu Old People's
      Programme.
AB  - INTRODUCTION: Yuendumu is a Warlpiri Aboriginal community 300 km north west of
      Alice Springs in Central Australia. Since emerging from the welfare period in the
      early 1970s, a range of services have evolved with the aim of developing a
      comprehensive community based aged care service. In 2000 Mampu Maninja-kurlangu
      Jarlu Patu-ku Aboriginal Corporation (Yuendumu Old Peoples Programme; YOPP)
      commenced operation to manage the developing services. This case study aims to
      describe, from the analytic standpoint of community control and cultural comfort,
      the main features of the 'Family Model of Care', which underpins the operations
      of the service and YOPP management processes. METHODS: Data were mostly generated
      from participant observation by the authors in the development and management of
      YOPP between 1993 and 2009. A literature review of Indigenous history and public
      health in Central Australia was also undertaken, which was supplemented by a
      review of Programme documentation, including evaluations, needs assessments and
      annual reports. RESULTS: The design and operations of YOPP are embodied in a
      documented 'Family Model of Care' which provides important lessons for the
      provision of aged care in a cross-cultural context. According to the concepts
      'community control' and 'cultural comfort' outlined in this article, mainstream
      services can function in a complementary and supportive manner with professional
      services being accountable and responsive to a local management system that is
      governed by the structures and norms of community tradition. CONCLUSIONS: The
      notions of 'cultural comfort' and 'community control' as operating principles
      have enabled YOPP to continue under the management of local people, sustain core
      cultural strengths and values, and meet the needs for increased quality of care
      for the aged in Yuendumu. This model of care emphasizes and recognizes paradigms
      of mutual competence between traditional and mainstream human service culture,
      and offers important lessons for improvement to the quality of aged care in
      remote Indigenous communities in Australia and elsewhere.

PMID- 21070088
TI  - The influence of loan repayment on rural healthcare provider recruitment and
      retention in Colorado.
AB  - INTRODUCTION: There is an ongoing shortage of rural healthcare providers relative
      to urban healthcare providers worldwide. Many strategies have been implemented to
      increase the distribution of rural healthcare providers, and financial incentives
      such as loan repayment programs have become popular means to both recruit and
      retain healthcare providers in rural communities. Studies detailing the effects
      of such programs on rural provider recruitment and retention are limited. The
      objective of this study was to assess the influence of loan repayment and other
      factors on the recruitment and retention of healthcare providers in rural
      Colorado, USA, and to compare the motivations and attitudes of these rural
      providers with their urban counterparts. METHODS: A survey was sent to 122
      healthcare providers who had participated in one of three loan repayment programs
      in Colorado between the years of 1992 and 2007: the Colorado Health Professional
      Loan Repayment Program; the Colorado Rural Outreach Program; and the Dental Loan
      Repayment Program of Colorado. Differentiation between rural and urban
      communities was accomplished by using the Rural Urban Commuting Area Codes
      developed by the University of Washington's Rural Health Research Center and
      Economic Research Service. Statistical analysis was performed using STATA from
      StataCorp. RESULTS: Of the 93 respondents included in the study, 57 worked in
      rural communities and 36 worked in urban communities during their programs. Of
      the rural participants, 74% were already working in or intending to work in an
      eligible community when they were made aware of the loan repayment program. Of
      those planning to work in a rural community regardless of any loan repayment
      option, 42% reported that the loan repayment program had an important influence
      on the specific community in which they chose to practice. Of the rural
      participants already working in a rural community, 38% reported loan repayment as
      being an important factor in their retention. The most important factors the
      rural providers cited for their recruitment were the location of the community,
      scope of practice, and family fit with the community. The most important factors
      for the urban providers were the location of the community, salary, and scope of
      practice. Of the rural providers, 36% attended rural high schools, while 9% of
      urban providers attended rural high schools. Of the rural providers who were
      planning on practicing in a rural area regardless of any loan repayment option,
      37% had attended rural high schools. Rural participants most often left their
      communities because their families wanted to move, personal or professional
      isolation, and dissatisfaction with the medical community. Of rural participants
      22% cited the desire for a higher income as an important reason to leave their
      communities, while the desire for a higher income was the most commonly cited
      reason for the urban providers. Rural retention rates were not influenced by past
      attendance at rural high schools or by intention to practice in a rural community
      regardless of loan repayment. CONCLUSIONS: Loan repayment programs targeting
      rural Colorado usually enroll providers who would have worked in a rural area
      regardless of loan repayment opportunities, but are likely to play a role in
      providers' choice of specific rural community for practice. They also appear to
      have a limited but important influence on rural provider retention, though
      financial concerns are generally less influential for non-retained rural
      providers than are family preferences and professional dissatisfaction.

PMID- 21070089
TI  - Primary Epstein-Barr virus infection with neurological complications.
AB  - Several case studies have reported on neurological complications caused by a
      primary Epstein-Barr virus (EBV) infection. We aimed to investigate the viral
      loads and the clinical and inflammatory characteristics of this disease entity.
      We evaluated all 84 cases in which the EBV polymerase chain reaction test (PCR)
      was requested on cerebrospinal fluid (CSF) for the period 2003-2008. Fourteen
      patients with proven neuroborreliosis served as the control group. Nine patients
      were diagnosed with a primary EBV infection and neurological symptoms (median age
      36 y; 4 male). Viral DNA copies in CSF were detected by PCR in 7 of 9 patients.
      The presenting symptoms were meningeal signs, epileptic insults,
      polyradiculomyelitis, polyradiculitis, and/or sudden cognitive disorders. All EBV
      cases had a pleocytosis with significantly increased mononuclear leukocytes as
      compared to the neuroborreliosis group (median 99% interquartile range (96-100%)
      versus 90% (86-97%). In cases with a primary EBV infection, viral loads ranged
      from 43 to 3202 copies/ml in CSF and from 61 to 15,595 copies/ml in serum.
      Seventy-eight percent of the cases had a positive PCR on CSF. This study provides
      criteria for diagnosing neurological disease during primary EBV infection.
      Primary EBV infections in immune competent persons can cause a broad range of
      neurological symptoms, with lymphocytic and monocytic inflammation both in blood
      and CSF.

PMID- 21070090
TI  - Noninvasive evaluation of endolymphatic space in healthy volunteers using
      magnetic resonance imaging.
AB  - CONCLUSIONS: A new method for noninvasive standard evaluation of normal
      endolymphatic space and endolymphatic hydrops using magnetic resonance imaging
      (MRI) is indicated. OBJECTIVE: To standardize the evaluation of endolymphatic
      space in the cochlea and the vestibule in healthy volunteers by applying
      noninvasive intratympanic gadolinium (Gd) perfusion through the eustachian tube
      and three-dimensional fluid-attenuated inversion recovery magnetic resonance
      imaging (3D-FLAIR MRI). METHODS: This was a prospective study. 3D-FLAIR MRI was
      performed with a 3 Tesla (3 T) unit 24 h after intratympanic administration of Gd
      through the eustachian tube in 20 healthy volunteers. Pure tone test and
      tympanometry were performed 24 h before Gd was administered, and 24 h and 1 month
      after Gd administration. RESULTS: Gd was present in the perilymph of the inner
      ear, which clearly displayed the endolymphatic space on 3D-FLAIR MRI with a
      visible borderline between the perilymph and the endolymph. In healthy
      volunteers, the normal value for the endolymphatic space in the cochlea ranged
      between 9% and 28%, and that in the vestibule was between 14% and 40%. No
      significant changes in pure tone test and tympanometry were noted.

PMID- 21070091
TI  - The efficacy of functional endoscopic sinus surgery in the evolution of fever of
      unknown origin in ICU patients.
AB  - CONCLUSION: Functional endoscopic sinus surgery (FESS) was found to be effective
      in treating fever of unknown origin (FUO) in intensive care unit (ICU) patients
      with rhinosinusitis, with 62% of patients showing improvement within 5 days of
      the procedure. OBJECTIVE: To correlate improvement in FUO with FESS drainage of
      the paranasal sinuses. METHODS: Fifty patients that developed FUO during ICU
      stay, with CT findings suggestive of rhinosinusitis, and showed no improvement in
      fever after clinical treatment underwent FESS for drainage of the paranasal
      sinuses and were evaluated for postoperative improvement of fever. RESULTS: The
      study sample consisted of 50 patients (74% of whom were male, mean age 48.1
      years). The most frequent diagnoses at ICU admission were tetanus, pulmonary
      disease, and cardiovascular disease. In all, 68% of patients underwent
      nasogastric or enteral intubation. CT scanning most commonly showed involvement
      of the sphenoid sinus. In 54% of cases, sinusitis was bilateral and extended
      throughout the maxillary, ethmoidal, and sphenoidal sinuses. Sinusectomy was
      performed in all patients, and pathological secretion in the paranasal sinuses
      was seen in 52% of patients during surgery. Gram-negative bacteria were the most
      commonly isolated organisms, followed by Gram-positive bacteria and fungi.
      Improvement of fever was found in 82% of patients after FESS; 38% of these
      improved within the first 48 h post-procedure, and the remaining 62% within the
      first 5 postoperative days.

PMID- 21070092
TI  - Ramsay Hunt syndrome with multicranial nerve involvement.
AB  - CONCLUSIONS: Ramsay Hunt syndrome (RHS) with multiple involvement of cranial
      nerves is more severe and intractable than RHS without such involvement.
      OBJECTIVES: Typically, RHS involves VII and VIII nerves and unilaterally, and RHS
      accompanied by multiple cranial neuropathy is very rare. We describe 11 patients
      who developed RHS with multicranial nerve involvement and we analyzed their
      clinical characteristics and compared them with those of patients with RHS not
      accompanied by multiple cranial neuropathy. METHODS: During the period 1995-2009,
      we treated 339 patients with RHS; of these, 11 patients had concurrent multiple
      cranial neuropathy. We assessed the clinical characteristics of RHS patients with
      and without multiple cranial neuropathy. RESULTS: The mean age of the 11 patients
      with multiple cranial neuropathy (6 men, 5 women) was 49.2 +/- 19.4 years,
      although 7 were aged 50 years or older. Eight patients had right-sided and three
      had left-sided facial paralysis. The initial degree of facial paralysis was House
      Brackmann (HB) grade IV in four patients (36.4%) and HB grade V in seven (63.6%).
      Six patients showed improvement in symptoms, whereas five (45.6%) showed no
      improvement. The recovery rates from facial paralysis in patients with and
      without multiple cranial neuropathy were 54.5% and 82.9%, respectively, and the
      complete recovery rates were 27.3% and 67.7%, respectively.

PMID- 21070093
TI  - Two conformational forms of target-bound iC3b that distinctively bind complement
      receptors 1 and 2 and two specific monoclonal antibodies.
AB  - INTRODUCTION: The complement system is an essential part of the immune system of
      vertebrates. The central event of the complement activation cascade is the
      sequential proteolytic activation of C3, which is associated with profound
      alterations in the molecule's structure and conformation and is responsible for
      triggering most of the biological effects of complement. MATERIAL AND METHODS:
      Here, we have studied the conformation of C3 fragments deposited onto an IgG
      coated surface from human serum during complement activation, using a set of
      unique monoclonal antibodies (mAbs) that are all specific for the C3dg portion of
      bound iC3b. RESULTS; We were able to identify two conformational forms of target
      bound iC3b: the first recognized by mAb 7D18.1, and the second by mAb 7D323.1.
      The first species of iC3b bound recombinant complement receptor 1 (CR1), while
      the second bound CR2. Since CR1 and CR2 are expressed by different subsets of
      leukocytes, this difference in receptor-binding capacity implies that there is a
      biological difference between the two forms of surface-bound iC3b. CONCLUSION: We
      propose that mAbs 7D18.1 and 7D323.1 can act as surrogate markers for CR1 and
      CR2, respectively, and that they may be useful tools for studying the immune
      complexes that are generated in various autoimmune diseases.

PMID- 21070094
TI  - The relationship between socio-demographic characteristics of patients and
      diagnostic delay in acute pulmonary thromboembolism.
AB  - BACKGROUND: In pulmonary thromboembolism (PE), delay to diagnosis is very common.
      In this study, we examined the role of patients and the socio-demographic
      characteristics in delayed diagnosis of PE. PATIENTS AND METHODS: We evaluated
      156 PE patients for the dates of symptom onset, the dates of first visit to a
      health institution and diagnosis, signs and symptoms, and the socio-demographic
      characteristics. Delays were analyzed using the Mann-Whitney U test, and the
      predictors were analyzed using logistic regression analysis. RESULTS: Of the
      patients, 60.3% visited a health institution within the first day of the
      symptoms. Mean time from symptoms to the first admission to a health institution
      (patient delay) was 2.04 +/- 3.89 days (median 0 day, range 0-30). Current
      smoking, a high level of education, and co-morbidity were associated with longer
      patient delays. The time interval from first symptom to the diagnosis (total
      delay) was 7.93 +/- 10.05 (median 4 days, range 0-45) days. While hypotension,
      syncope, and previous surgery/trauma were significantly associated with a shorter
      total delay, a previous visit to any health institution was associated with
      longer total delay. CONCLUSION: In conclusion, although some socio-demographic
      characteristics of patients such as smoking, educational status, and co-morbid
      diseases were found to be associated with delayed visit to any health
      institution, our results showed that physician or health system delays were more
      prominent in delayed diagnosis of PE.

PMID- 21070095
TI  - Improving insulin resistance in obese youth: choose your measures wisely.
AB  - OBJECTIVE: The purpose of this investigation was to compare the homeostasis model
      assessment of insulin resistance (HOMA-IR) to more direct measures of insulin
      action before and after lifestyle interventions in obese Latino youth. STUDY
      DESIGN: Eleven obese Latino boys (age 15.1 +/- 1.6 years, body mass index (BMI)
      percentile 97.3 +/- 3.5%) and twenty obese Latina girls (age 14.7 +/- 1.8 years,
      BMI percentile 96.6 +/- 3.6%) participated in two distinct lifestyle
      interventions. Boys participated in a 16-week exercise intervention and girls
      participated in a 12-week nutrition education program. Insulin sensitivity was
      determined by the frequently sampled intravenous glucose tolerance test (FSIVGTT)
      in boys and by a 3-hour oral glucose tolerance test with multiple sampling
      calculations for the whole-body insulin sensitivity index (WBISI) in girls. HOMA
      IR was measured for both groups. RESULTS: HOMA-IR was correlated at baseline to
      the FSIVGTT (r = -0.57, p = 0.07) and the WBISI (r = -0.78, p<0.01) and at follow
      up (FSIVGTT: r = -0.81, p<0.003; WBISI: r = -0.71, p = 0.001). Post-intervention,
      insulin sensitivity increased 45% in the boys and 34% in the girls; however,
      these improvements were not reflected by significant changes in HOMA-IR.
      CONCLUSIONS: Improvements in insulin sensitivity following an intervention
      measured either by the FSIVGTT or an OGTT were not detected by HOMA-IR.
      Researchers and clinicians should exercise caution in relying on fasting indices,
      such as HOMA-IR, to determine the impact of lifestyle interventions on insulin
      sensitivity in overweight youth.

PMID- 21070096
TI  - Impact of asthma controller medications on medical and economic resource
      utilization in adult asthma patients.
AB  - OBJECTIVE: To compare asthma-related resource utilization, adherence and costs
      among adults prescribed asthma controller regimens. RESEARCH DESIGN AND METHODS:
      Medical and pharmacy claims from a US managed-care claims database were used to
      identify adults (18-56 years) initiating asthma controller therapy. Patients had
      2 years continuous enrollment and >= 1 medical claims for asthma (ICD9: 493.xx)
      (January 2004 - March 2009). Asthma exacerbations, short-acting beta-agonist
      (SABA) fills, adherence (MPR >= 0.80) and asthma-related costs were assessed for
      1 year after the initial asthma controller medication claim. Separate logistic
      and negative binomial regression models for monotherapy and combination therapy
      were developed to examine the impact of controller therapy on outcomes. RESULTS:
      A total of 28 074 patients [inhaled corticosteroids (ICS) (26.3%), leukotriene
      modifiers (LM) (23.2%), ICS  +  long acting beta-agonist (LABA) (48.5%), ICS + LM
      (2%)] were included. LM patients had lower odds of >= 6 SABA fills (OR(adj) =
      0.83, 95% CI: 0.73-0.96) and lower rates of asthma exacerbations (RR(adj) = 0.82,
      0.75-0.89) vs. ICS patients. Odds of >= 6 SABA fills were similar for ICS + LM
      vs. ICS + LABA (OR(adj) = 1.3, 0.96-1.76); the rate of asthma exacerbations was
      greater for ICS + LM compared with ICS + LABA (OR(adj) = 1.4, 1.2-1.6). The
      proportion adherent was greatest for LM (14.9%) and ICS + LABA (4.1%). LM
      patients had higher unadjusted pharmacy costs, but lower medical costs compared
      to ICS patients. For combination therapy, ICS + LM had higher unadjusted mean
      medical and pharmacy costs vs. ICS + LABA. Higher adjusted mean total costs in
      the post-index period were observed for LM vs. ICS patients ($837 vs. 684) and
      for ICS + LM vs. ICS + LABA patients ($1223 vs. 873). CONCLUSIONS: LM monotherapy
      was associated with lower medical costs but higher total costs resulting from
      greater treatment adherence. Conversely, higher costs for ICS + LM resulted from
      greater exacerbations compared to ICS + LABA despite similar adherence. Higher
      total costs with LM were due to drug costs. Precise utilization of the
      medications filled by patients could not be determined.

PMID- 21070097
TI  - New guidelines for topical NSAIDs in the osteoarthritis treatment paradigm.
AB  - BACKGROUND: Osteoarthritis (OA), the most common form of arthritis, often affects
      hands, hips, and knees and involves an estimated 26.9 million US adults. Women
      have a higher prevalence of OA, and the risk of developing OA increases with age,
      obesity, and joint malalignment. OA typically presents with pain and reduced
      function. Therapeutic programs are often multimodal and must take into account
      pharmaceutical toxicities and patient comorbidities. For example, nonsteroidal
      anti-inflammatory drugs (NSAIDs) are associated with cardiovascular,
      gastrointestinal, and renal adverse events. Topical NSAIDs offer efficacy with
      reduced systemic drug exposure. RESEARCH DESIGN AND METHODS: This is a review of
      current guideline recommendations regarding the use of topical NSAIDs in OA of
      the hand and knee. Articles were identified by PubMed search (January 1, 2000 to
      May 21, 2010). RESULTS: Several current guidelines for management of OA recommend
      topical NSAIDs, indicating them as a safe and effective treatment. One guideline
      recommends that topical NSAIDs be considered as first-line pharmacologic therapy.
      A US guideline for knee OA recommends topical NSAIDs in older patients and in
      patients with increased gastrointestinal risk. CONCLUSIONS: The consensus across
      US and European OA guidelines is that topical NSAIDs are a safe and effective
      treatment for OA. Because the research base on topical NSAIDs for OA is small,
      guidelines will continue to evolve.

PMID- 21070098
TI  - The prevalence of celiac disease in Europe: results of a centralized,
      international mass screening project.
AB  - INTRODUCTION: Although the prevalence of celiac disease (CD) has been extensively
      investigated in recent years, an accurate estimate of CD frequency in the
      European population is still lacking. The aims of this study were: 1) to
      establish accurately the prevalence of CD in a large sample of the European
      population (Finland, Germany, Italy, and UK), including both children and adults;
      and 2) to investigate whether the prevalence of CD significantly varies between
      different areas of the European continent. MATERIALS AND METHODS: Samples were
      drawn from the four populations. All 29,212 participants were tested for CD by
      tissue transglutaminase (tTG) antibody test. Positive and border-line findings
      were further tested for serum endomysial antibodies (EMA). All serological
      determinations were centrally performed. Small-bowel biopsies were recommended to
      autoantibody-positive individuals. Previously diagnosed cases were identified.
      RESULTS: The overall CD prevalence (previously diagnosed plus anti-tTG and EMA
      positives) was 1.0% (95% CI 0.9-1.1). In subjects aged 30-64 years CD prevalence
      was 2.4% in Finland (2.0-2.8), 0.3% in Germany (0.1-0.4), and 0.7% in Italy (0.4
      1.0). Sixty-eight percent of antibody-positive individuals showed small-bowel
      mucosal changes typical for CD (Marsh II/III lesion). CONCLUSIONS: CD is common
      in Europe. CD prevalence shows large unexplained differences in adult age across
      different European countries.

PMID- 21070099
TI  - Healthcare costs in postmenopausal women with hormone-positive metastatic breast
      cancer.
AB  - OBJECTIVES: This study examines costs for postmenopausal women with hormone
      receptor positive (HR+) metastatic breast cancer (mBC). METHODS: Data were
      obtained from the IHCIS National Managed Care Benchmark Database from 1/1/2001 to
      6/30/2006. Women aged 55-63 years were selected for the study if they met the
      inclusion criteria, including diagnoses for breast cancer and metastases, and at
      least two fills for a hormone medication. Patients were followed from the onset
      of metastases until the earliest date of disenrollment from the health plan or
      6/30/2006. Patient characteristics were examined at time of initial diagnoses of
      metastases, while costs were examined post-diagnosis of metastases and prior to
      receipt of chemotherapy (pre-chemotherapy initiation period) and from the date of
      initial receipt of chemotherapy until end of data collection (post-chemotherapy
      initiation period). Costs were adjusted to account for censoring of the data.
      RESULTS: The study population consisted of 1,266 women; mean (SD) age was 59.05
      (2.57) years. Pre-chemotherapy initiation, unadjusted inpatient, outpatient, and
      drug costs were $4,392, $47,731, and $5,511, while these costs were $4,590,
      $57,820, and $38,936 per year, respectively, post-chemotherapy initiation. After
      adjusting for censoring of data, total medical costs were estimated to be $55,555
      and $70,587 in the first 12 months and 18 months, respectively in the pre
      chemotherapy initiation period. Post-chemotherapy initiation period, 12-month and
      18-month adjusted total medical costs were estimated to be $87,638 and $130,738.
      LIMITATIONS: The use of an administrative claims database necessitates a reliance
      upon diagnostic codes, age restrictions, and medication use, rather than formal
      assessments to identify patients with post-hormonal women with breast cancer.
      Furthermore, such populations of insured patients may not be generalizable to the
      population as a whole. CONCLUSIONS: These findings suggest that healthcare
      resource use and costs - especially in the outpatient setting - are high among
      women with HR+ metastatic breast cancer.

PMID- 21070100
TI  - Predicting cardiovascular risk in young adulthood from the metabolic syndrome,
      its component risk factors, and a cluster score in childhood.
AB  - OBJECTIVE: The value of metabolic syndrome (MetS) in childhood and adolescence
      and its stability into young adulthood have been questioned. This study compared
      the MetS in late childhood (mean age 13) versus a cluster score of the MetS
      components as predictors of young adult (mean age 22) cardiovascular risk.
      METHODS: Anthropometrics, blood pressure, lipid profile, and insulin resistance
      (insulin clamp) were obtained in 265 individuals at mean ages 13 and 22. The MetS
      was defined dichotomously by current pediatric and adult criteria. The MetS
      cluster score used the average of deviates of the MetS components standardized to
      their means and standard deviations at mean age 13. RESULTS: The MetS was rarely
      present at mean age 13 and did not predict MetS at mean age 22 but identified
      individuals who continued to have adverse levels of risk factors at mean age 22.
      In contrast to the standard MetS definition, the MetS cluster score tracked
      strongly and at mean age 22 was significantly higher in the individuals with MetS
      at mean age 13 (0.78 +/- 0.71) than those without MetS at mean age 13 (0.09 +/-
      0.70, p <0.0001). CONCLUSIONS: Although the MetS at mean age 13, using the
      conventional definition, is not a reliable method for predicting the MetS at mean
      age 22, it does predict adverse levels of cardiovascular risk factors. A cluster
      score, using the MetS components as continuous variables, is more reliable in
      predicting young adult risk from late childhood.

PMID- 21070102
TI  - Preventing post traumatic stress disorder: are drugs the answer?
AB  - In the field of traumatic stress, chemoprophylaxis is a term that is often used
      but rarely well understood. There has been no shortage of debate on the issue,
      but few rigorous studies to ground the discussion. The purpose of the current
      paper is to explore the issues surrounding this contentious area. Databases
      including PubMed, PsychArticles and Web of Knowledge were searched using the key
      words 'chemo or pharmaco', 'prevention or prophylaxis', and 'PTSD or post
      traumatic stress'. Relevant journals and reference lists of the papers obtained
      through this search were scanned for additional references. Studies that
      investigated the use of pharmacotherapy to prevent the onset of post-traumatic
      stress disorder were considered for this paper. Studies that examined the
      treatment of established PTSD were excluded. A total of 15 empirical studies were
      included in the review (including five randomized controlled trials), and twice
      as many non-data-driven papers. Evidence for the prophylactic use of alcohol,
      morphine, propranolol, and hydrocortisone is presented, followed by a discussion
      of the many challenges of using pharmacological interventions in this context.
      While attention to this issue has increased in recent times, the dearth of
      empirical data has done little to further the field. Larger studies are indicated
      following small trials with medications such as propranolol and hydrocortisone.
      There remain a number of ethical and practical questions to be answered before
      the widespread use of chemoprophylaxis can be recommended.

PMID- 21070101
TI  - JAK3 pathway is constitutively active in B-lineage acute lymphoblastic leukemia.
AB  - In this article, we report that primary leukemic B-cell precursors from B-lineage
      acute lymphoblastic leukemia (ALL) patients overexpress multiple JAK3-activating
      cytokines as well as their receptors. We also show that amplified expression of
      JAK3 pathway genes in B-lineage ALL is associated with steroid resistance and
      relapse. Our findings further demonstrate that several different diagnostic
      classes of B-lineage lymphoid malignancies exhibit upregulated expression of JAK3
      pathway genes, which are associated with an overexpression of genes for JAK3
      stimulatory cytokines with concomitant deficiency of JAK3-inhibitory signaling
      molecules. Thus, despite the rare occurrence of activating JAK3 mutations, JAK3
      appears to be constitutively active and represents a viable molecular target in
      the treatment of a broad range of B-lineage lymphoid malignancies, including B
      lineage ALL.

PMID- 21070103
TI  - Mental health first aid training by e-learning: a randomized controlled trial.
AB  - OBJECTIVE: Mental Health First Aid training is a course for the public that
      teaches how to give initial help to a person developing a mental health problem
      or in a mental health crisis. The present study evaluated the effects of Mental
      Health First Aid training delivered by e-learning on knowledge about mental
      disorders, stigmatizing attitudes and helping behaviour. METHOD: A randomized
      controlled trial was carried out with 262 members of the Australian public.
      Participants were randomly assigned to complete an e-learning CD, read a Mental
      Health First Aid manual or be in a waiting list control group. The effects of the
      interventions were evaluated using online questionnaires pre- and post-training
      and at 6-months follow up. The questionnaires covered mental health knowledge,
      stigmatizing attitudes, confidence in providing help to others, actions taken to
      implement mental health first aid and participant mental health. RESULTS: Both e
      learning and the printed manual increased aspects of knowledge, reduced stigma
      and increased confidence compared to waiting list. E-learning also improved first
      aid actions taken more than waiting list, and was superior to the printed manual
      in reducing stigma and disability due to mental ill health. CONCLUSIONS: Mental
      Health First Aid information received by either e-learning or printed manual had
      positive effects, but e-learning was better at reducing stigma.

PMID- 21070104
TI  - Pharmacists' beliefs about treatments and outcomes of mental disorders: a mental
      health literacy survey.
AB  - OBJECTIVES: To assess the beliefs of pharmacists about the helpfulness of
      interventions for schizophrenia and depression. METHODS: A survey instrument
      containing a measure of mental health literacy was mailed to a random sample of
      2000 pharmacists registered with the Pharmacy Board of New South Wales in
      November 2009. Vignettes of a person with either depression or psychosis were
      presented, followed by questions related to the recognition of the disorder, the
      helpfulness of various interventions, prognosis with and without professional
      help, the person's long-term functioning in various social roles and the
      likelihood of the person being discriminated against. RESULTS: A total of 391
      responses were received (response rate 19.5%). The majority of pharmacists
      correctly identified depression (92%) with fewer recognizing schizophrenia (79%).
      Pharmacists rated medicine use highly for both schizophrenia and depression but
      were also positive about the use of psychological therapies and lifestyle
      interventions. Pharmacists had negative views about admission to a psychiatric
      ward and the use of electroconvulsive therapy (ECT). However, younger pharmacists
      had significantly more positive views on the use of ECT (p = 0.001). The majority
      of pharmacists (74%) thought discrimination by the community was highly likely
      and rated long-term prognosis as poor without appropriate professional help.
      Their views on the likelihood of specific negative outcomes were mixed, with many
      pharmacists not recognizing the risk of suicide in schizophrenia and depression.
      However, both female (p = 0.002) and younger pharmacists (p < 0.001) were
      significantly more inclined to rate the likelihood of suicide as more likely in a
      person with schizophrenia or depression. CONCLUSIONS: The majority of pharmacists
      had a high degree of mental health literacy as indicated by the correct
      identification of, and support for evidence-based interventions for mental
      illnesses. Pharmacists should be aware that their attitudes and stigma towards
      mental illness may impact on the patient care they provide.

PMID- 21070105
TI  - On the meaning of change in a clinician's routine measure of outcome: HoNOSCA.
AB  - OBJECTIVE: With the advent of routine outcomes across Australia and New Zealand,
      clinicians, managers, parents and children will be interested in change on these
      measures. This paper presents a number of approaches and the implications.
      METHOD: Health of the Nations Outcome Scales for Children and Adolescents
      (HoNOSCA) collected during clinical practice for 911 patients were examined for
      changes over time, clinical significance, treatment status, effect size, and
      reliable and clinically significant change. RESULTS: Statistically significant
      changes in symptom severity were found related to treatment status and to changes
      in the number of clinically significant scales. An effect size of almost one
      standard deviation was noted and the proportion of patients who improved was
      examined. While the reliable change index was calculated, there are clinical
      complications with this approach. The impact of the capacity to change on
      specific scales illustrates a critical issue in describing outcomes. CONCLUSION:
      From a number of perspectives, change in HoNOSCA total and scale scores is valid.
      However, several clinical dilemmas must be faced in deciding which approach
      should be used. The implications of these choices may affect clinicians,
      patients, carers and managers in understanding change.

PMID- 21070106
TI  - Practitioner perceptions of Skills for Psychological Recovery: a training
      programme for health practitioners in the aftermath of the Victorian bushfires.
AB  - OBJECTIVE: Following the February 2009 Victorian bushfires, Australia's worst
      natural disaster, the Australian Centre for Posttraumatic Mental Health, in
      collaboration with key trauma experts, developed a three-tiered approach to
      psychological recovery initiatives for survivors with training specifically
      designed for each level. The middle level intervention, designed for delivery by
      allied health and primary care practitioners for survivors with ongoing mild
      moderate distress, involved a protocol still in draft form called Skills for
      Psychological Recovery (SPR). SPR was developed by the US National Center for
      PTSD and US National Child Traumatic Stress Network. This study examined health
      practitioner perceptions of the training in, and usefulness of, SPR. METHODS:
      From a range of disciplines 342 health practitioners attended one of 25 one-day
      workshops on the delivery of SPR. Perceptions of evidence-based care and
      attitudes to manualized interventions were assessed at the commencement of the
      workshop. Following the workshop, participants' perceptions of their confidence
      in applying, and perceived usefulness of, each module were assessed. A subset of
      20 participants recorded their ongoing use of SPR recording 61 cases. RESULTS:
      The vast majority of participants rated the SPR modules as useful for survivors
      of disasters and expressed confidence in implementing the intervention following
      the training. Participants' pre-workshop attitudes towards evidence-based care
      and manualized interventions affected their perceptions of the usefulness of the
      protocol. The 'Promoting positive activities' and 'Rebuilding healthy social
      connections' modules were least influenced by variations in these perceptions.
      CONCLUSIONS: This study provides preliminary evidence that SPR is perceived by
      health providers from varying disciplines and paradigms as an acceptable and
      useful intervention for disaster survivors with moderate levels of mental health
      difficulties. Future SPR dissemination efforts may benefit from focusing on
      modules with the strongest evidence base and which are most amenable to
      practitioner acceptance and uptake.

PMID- 21070107
TI  - Association of demographic characteristics, symptomatology, retrospective and
      prospective memory, executive functioning and intelligence with social
      functioning in schizophrenia.
AB  - OBJECTIVE: The objective of this study was to explore the influence of socio
      demographic and clinical factors and neurocognitive variables (i.e. prospective
      and retrospective memory, executive functioning, and intelligence) on social
      functioning in Chinese schizophrenia patients. METHODS: The study sample
      comprised 110 Chinese schizophrenia patients. Their clinical condition and social
      functioning were evaluated with the Brief Psychiatric Rating Scale (BPRS) and the
      Functional Needs Assessment (FNA), respectively. Three prospective memory (PM)
      tasks (time-, event-, and activity-based), three tests of executive functioning
      (the Design Fluency Test [DFT], Tower of London [TOL], and Wisconsin Card Sorting
      Test [WCST]), one test of intelligence (Raven's Progressive Matrices), and two
      retrospective memory (RM) tasks (the immediate and delayed recall conditions of
      the Logical Memory subtest of the Wechsler Memory Scales-Revised [WMS-R]) were
      administered to all patients. RESULTS: In correlation analyses higher education
      and better performance on the WCST (categories completed) and the Logical Memory
      subtests (delayed and immediate) of the WMS-R are significantly correlated with
      better social functioning, whereas a lower WCST score (perseverative errors) and
      more severe negative symptoms are associated with poorer social functioning.
      Multiple linear regression analysis revealed that higher education and a lower
      WCST score (perseverative errors) independently contribute to better social
      functioning. CONCLUSIONS: Unexpectedly, most socio-demographic and clinical
      factors do not seem to have a significant impact on social functioning of Chinese
      schizophrenia patients living in a Chinese society. Negative symptoms and certain
      cognitive deficits were the main predictors of social functioning and they should
      be the main targets for antipsychotic treatment and psychosocial interventions to
      improve social adjustment in Chinese schizophrenia patients.

PMID- 21070108
TI  - Australian and Canadian mental health Acts compared.
AB  - OBJECTIVE: The main objective of this paper is to compare the mental health Acts
      of the eight Australian jurisdictions and the 13 Canadian jurisdictions on three
      major issues: involuntary admission criteria, treatment authorization/consent and
      compulsory treatment in the community, in the light of international trends
      towards patients' rights. METHOD: The legislation was examined against the
      background of rights instruments such as the Canadian Charter of Rights and
      Freedoms and the United Nations Convention on the Rights of Persons with
      Disabilities. RESULTS: It was found that some Canadian involuntary admission
      criteria require the likelihood of bodily harm whereas all Australian Acts have
      broad harm and deterioration criteria. Unlike all Australian jurisdictions, some
      Canadian jurisdictions allow for the refusal of treatment that may be required
      for discharge. In addition, Canadian community treatment orders are much more
      restrictive than in Australia because they require a person to have considerable
      previous hospitalization despite meeting the committal criteria. Australian
      jurisdictions can use community treatment orders as a least restrictive
      alternative to inpatient status without prior hospitalization. CONCLUSIONS: The
      paper concludes that there are significant philosophical differences regarding
      the purpose of involuntary admission between Australian and some Canadian
      jurisdictions where treatment refusal is possible. Australian mental health Acts
      have a relatively stronger 'treatment' focus than some Canadian Acts. The
      apparently stronger 'rights' focus of some Canadian laws (such as the permission
      of treatment refusal) can paradoxically result in a denial of liberty rights. The
      way in which the relevant legislation is shaped in both countries will
      increasingly be affected by international trends towards the rights of
      individuals with disabilities.

PMID- 21070109
TI  - Is there evidence of 'hardening' among Australian smokers between 1997 and 2007?
      Analyses of the Australian National Surveys of Mental Health and Well-Being.
AB  - OBJECTIVES: To use data from the 1997 and 2007 National Surveys of Mental Health
      and Well-Being (NSMHWB) to assess whether Australian smokers in 2007 have higher
      rates of mental distress and social disadvantage than smokers in 1997. METHOD: We
      compared symptoms of mental distress and social disadvantage in Australian
      smokers in the 1997 and 2007 National Surveys of Mental Health and Well-Being (N
      = 10 373 in 1997 and N = 8135 in 2007). Both surveys used multistage probability
      samples of Australians living in private dwellings. Participants were classified
      into smokers and non-smokers (which included former and never smokers). We used
      the Kessler 10 (K10) symptom score to classify smokers into three levels of
      psychological distress (low, medium or high) and socioeconomic disadvantage was
      measured using an area-based index of relative disadvantage converted into
      quintiles. We used logistic regressions to: (i) examine associations between
      smoking status (smoker/non-smoker) and psychological distress and socioeconomic
      disadvantage in 1997 and 2007 surveys; and (ii) to test whether the prevalence of
      psychological distress and social disadvantage among smokers increased between
      1997 and 2007. RESULTS: Psychological distress and social disadvantage were more
      common among smokers than non-smokers in both surveys but there was no evidence
      that the prevalence of psychological distress or social disadvantage was more
      common among smokers in 2007 than in 1997. CONCLUSION: We find no evidence that
      the declining smoking prevalence in Australia (over the last decade) has been
      accompanied by a 'hardening' of continuing smokers in terms of rates of mental
      disorders and socioeconomic disadvantage.

PMID- 21070110
TI  - Reducing impulsivity in repeat violent offenders: an open label trial of a
      selective serotonin reuptake inhibitor.
AB  - BACKGROUND: The association between serotonergic dysfunction and aggression has
      prompted the use of selective serotonin re-uptake inhibitors (SSRIs) as a means
      of controlling impulsive violent behaviour. The aim of the current study was to
      examine the feasibility of using an SSRI to treat impulsivity in a group of
      repeat violent offenders. METHODS: Potential participants were recruited from
      three magistrates' court complexes in the Sydney metropolitan area and all had
      histories of violent offending (at least one prior conviction for a violent
      offence). Those who scored highly on the Barratt Impulsivity Scale (BIS-11),
      passed medical and psychiatric evaluations and consented to treatment were
      prescribed sertraline (Zoloft) over a three month period. RESULTS: Thirty-four
      individuals commenced the trial, with 20 completing the three month intervention.
      Reductions were observed across a range of behavioural measures from baseline to
      3 months: impulsivity (35%), irritability (45%), anger (63%), assault (51%),
      verbal-assault (40%), indirect-assault (63%), and depression (62%). All those who
      completed the three month trial requested to continue sertraline under the
      supervision of their own medical practitioner. CONCLUSION: Our findings suggest
      that treating impulsive violent individuals in the criminal justice system with
      an SSRI is a potential treatment opportunity for this population. An adequately
      powered randomized control trial of this intervention is warranted.

PMID- 21070111
TI  - Quetiapine overdose.

PMID- 21070112
TI  - Venlafaxine associated urinary symptoms.

PMID- 21070113
TI  - Neuroleptic sensitivity in the elderly: lesson from clinical practice.

PMID- 21070115
TI  - Health advocacy training: why are physicians withholding life-saving care?
AB  - The societal responsibility of physicians to be health advocates, both at the
      population and patient level is necessary to positively influence public health
      and policy. Physicians must commit to learn about policy reform and the
      legislative process. Several regulatory physician organizations emphasize the
      importance of health. In addition, the Association of American Medical Colleges'
      (AAMC) Medical Schools Objectives Project, the Medical Council of Canada
      Qualifying Examination objectives and several Canadian medical schools outline
      advocacy as an objective. As a result, several US medical schools have designed
      and incorporated health advocacy into their curricula. Canadian medical schools,
      however, have been lagging behind. To address this deficiency, the University of
      Alberta and the University of Calgary hosted the 1st Annual Alberta Political
      Action Day (PAD) to engage medical students in advocacy and the policy making
      process. The two-day time requirement of PAD makes it an efficient model to
      incorporate health advocacy into the already demanding undergraduate medical
      curriculum. Canadian medical schools must follow the American example and further
      integrate initiatives such as PAD to teach health advocacy. The skills developed
      will enhance student's comprehension of how they can shape health policy and
      truly advocate for optimal patient care.

PMID- 21070114
TI  - A stable producer cell line for the manufacture of a lentiviral vector for gene
      therapy of Parkinson's disease.
AB  - ProSavin is an equine infectious anemia virus vector-based gene therapy for
      Parkinson's disease for which inducible HEK293T-based producer cell lines (PCLs)
      have been developed. These cell lines demonstrate stringent tetracycline
      regulated expression of the packaging components and yield titers comparable to
      the established transient production system. A prerequisite for the use of PCL
      derived lentiviral vectors (LVs) in clinical applications is the thorough
      characterization of both the LV and respective PCL with regard to identity and
      genetic stability. We describe the detailed characterization of two ProSavin PCLs
      (PS5.8 and PS46.2) and resultant ProSavin vector. The two cell lines demonstrate
      stable production of vector over a time period sufficient to allow generation of
      master and working cell banks, and subsequent large-scale vector production.
      ProSavin generated from the PCLs performs comparably in vivo to that produced by
      the standard transient transfection process with respect to transduction
      efficiency and immunogenicity. The development of ProSavin PCLs, and the detailed
      characterization described here, will aid the advancement of ProSavin for
      clinical application.

PMID- 21070116
TI  - Aligning teaching practices with an understanding of quality teaching: a faculty
      development agenda.
AB  - BACKGROUND: To guide the future faculty development practices in a better manner,
      it is important to determine how clinical teachers perceive their own skill
      development. AIM: The objective of this study was to examine the extent to which
      clinical teachers aligned their teaching practices, as measured with a self
      rating instrument, with their understanding of what constitutes good clinical
      teaching. METHOD: A sample of 1523 residents and 737 faculty members completed
      the clinical teaching perception inventory (CTPI) online and ranked 28 single
      word descriptors that characterized clinical teachers along a seven-point scale
      in two measures, "My Ideal Teacher" and "Myself as a Teacher." RESULTS: Faculty
      and residents showed strikingly similar discrepancies, in both their magnitudes
      and directions, between their ratings of "My Ideal Teacher" and those of "Myself
      as a Teacher." Both residents and faculty found it most difficult to develop the
      stimulating, well-read, and innovative nature to meet their own standards.
      CONCLUSIONS: Data did not support our hypothesis that faculty would demonstrate
      stronger congruence between "My Ideal Teacher" and "Myself as a Teacher" than
      residents. Medical faculty would benefit from future faculty development
      practices that are designed to assist them in becoming stimulating, well-read,
      and innovative teachers, while using less control and caution in their teaching.

PMID- 21070117
TI  - Improving lecture skills: a time-efficient 10-step pedagogical consultation
      method for medical teachers in healthcare professions.
AB  - BACKGROUND: Staff development initiatives proposed over the past few decades
      have, for the most part, suggested training environments such as workshops, short
      courses and seminar series. However, for many healthcare professionals, lecturing
      constitutes an ancillary activity, and a full-time occupation in the healthcare
      industry makes participation in such time-consuming programmes difficult to
      envision. AIM: To develop and offer for critical review a time-efficient
      pedagogical consultation method to improve lecture skills for medical teachers of
      healthcare professions. METHODS: Medical education literature was reviewed for
      factors known to facilitate successful pedagogical consultations. The result of
      this research was used to define the procedure of a consultation methodology. In
      subsequent trial runs, the consultation procedure was tested with eight
      healthcare professionals hired for lecturing in bachelor courses of healthcare
      professions. RESULTS: The key elements of successful pedagogical consultations
      were isolated in the literature, and a 10-step consultation method was developed
      based on specific methodological components. Eight trial runs indicated
      feasibility, time-efficiency and effectiveness of the method. CONCLUSION: The
      pedagogical consultation method presented here can help teachers to improve their
      lecture skills. It is a feasible model which can be easily adopted by medical
      educators to support staff development activities.

PMID- 21070118
TI  - Virtual worlds: a new opportunity for people with lifelong disability?

PMID- 21070119
TI  - Negative association of Epstein-Barr virus or herpes simplex virus-1 with
      tumefactive central nervous system inflammatory demyelinating disease.
AB  - Central nervous system (CNS) demyelination has been suggested to be associated
      with infections caused by the Epstein-Barr virus (EBV) or herpes simplex virus
      (HSV)-1. CNS inflammatory demyelinating disease (IDD) rarely presents as a large
      lesion. We evaluated samples of serum and cerebrospinal fluid (CSF) by enzyme
      linked immunosorbent assay to detect recent infection with these viruses and
      analyzed CSF and brain specimens by polymerase chain reaction (PCR) or
      immunohistochemical studies for evidence of these viruses in three patients with
      biopsy-proven CNS IDD. The results of PCR tests for EBV and HSV in CSF or brain
      specimens were negative. Elevated anti-EBV or -HSV antibody levels were not found
      in serum or CSF in any patient. Immunohistochemical studies showed that IDD
      lesions were negative for latent membrane protein (LMP)-1, Epstein-Barr nuclear
      antigen (EBNA)-2, and EBNA noncoding RNA (EBER)-1. These results suggest a
      negative association between CNS IDD and EBV or HSV.

PMID- 21070120
TI  - Dynamic QT/RR relationship in post-myocardial infarction patients with and
      without cardiac arrest.
AB  - OBJECTIVES: Changes in QT interval dynamicity may be associated with
      susceptibility to ventricular fibrillation (VF) after myocardial infarction (MI).
      We tested the hypothesis that dynamic QT/RR relationship might differ between
      post-MI patients with and without a history of VF. We also evaluated the
      influence of negative T-waves on the assessment of QT/RR relationship. DESIGN: We
      reviewed Holter recordings from 37 post-MI patients resuscitated from VF not
      associated with new MI (VF group) and 30 patients after MI without known
      sustained ventricular arrhythmias (control group). With an automated computerized
      program, we measured QT interval dynamicity as the mean QT/RR slope and as the
      maximal QT/RR slope determined at stable heart rates. RESULTS: The mean QT/RR
      slope was 0.20 +/- 0.08 in control group and 0.15 +/- 0.09 in VF group (p=0.01)
      whereas corresponding maximal QT/RR slope values were 0.42 +/- 0.20 and 0.33 +/-
      0.18 (p=0.01), respectively. Thirteen control patients (43%) and 22 VF patients
      (59%) showed only negative or both positive and negative T-waves (p=0.45). Mean
      QT/RR slope values were similar irrespective of T-wave polarity whereas maximal
      QT/RR slopes were steeper in cases with both positive and negative T-waves. Cases
      showing T-waves of both positive and negative polarity exhibited greatest
      intersubject variability of both QT/RR slope values. CONCLUSIONS: Lower mean
      QT/RR slope may be associated with a risk of VF after MI. A detailed assessment
      and definition of differing T-wave polarities is essential in evaluating the
      QT/RR relation in post-MI patients.

PMID- 21070121
TI  - Effects of stimulation rate on modulation detection and speech recognition by
      cochlear implant users.
AB  - OBJECTIVE: This study investigated the effect of low to moderate electrical
      stimulation rates (275, 350, 500 and 900 pps/ch) on modulation detection ability
      of cochlear implant subjects, and the relationship between modulation detection
      and speech perception as a function of rate. DESIGN: A repeated ABCD experimental
      design for the four rate conditions was employed. A sinusoidally amplitude
      modulated acoustic signal was presented to the audio input of a research
      processor. Stimuli were presented at an acoustic level that produced electrical
      levels close to the subjects' most comfortable level (MCL) of stimulation and at
      an acoustic level 20 dB below this. STUDY SAMPLE: Ten postlingually deaf adult
      users of the Nucleus CI24 cochlear implant participated. RESULTS: Acoustic
      modulation detection thresholds (MDTs), averaged across the subject group, were
      significantly better for rates of 500 pps/ch compared to the other rates examined
      for stimuli presented at MCL. In addition, there was a significant relation
      between speech perception in noise and acoustic MDTs at MCL. CONCLUSIONS: The
      benefits obtained in speech perception and modulation detection as a function of
      rate were attributed to an increased electrical dynamic range as a function of
      stimulation rate, at least for rates up to 500 pps/ch.

PMID- 21070122
TI  - Size distribution of embolic material produced at aortic cross-clamp
      manipulation.
AB  - OBJECTIVES: The association between aortic atherosclerosis and neurological
      damage during cardiac surgery is well recognized. The purpose was here to analyze
      the size distribution of particles produced at cross-clamp manipulation of the
      ascending aorta. DESIGN: A human cadaveric aortic perfusion model of retrograde
      design was applied (n=27). With this model, washout samples were collected from
      the pressurized ascending aorta during cross clamp manipulation. Before the
      experiment, the aorta was flushed to remove debris and with a baseline sample
      collected. The cross-clamp was opened to collect ten repeated aliquots with
      dislodged particles. Collected washout samples were evaluated by digital image
      analysis and microscopy. RESULTS: Cross-clamping produced a significant output of
      particles, which was seen for size intervals of 1 mm and smaller (p=0.002 to
      p=0.022). In all size intervals the particle output correlated with the degree of
      overall aortic calcification (p=0.002 to p=0.025). The model generated
      substantially more small-size particles than large debris (p<0.010). CONCLUSIONS:
      Aortic clamping was here verified to dislodge aortic debris which correlated with
      the degree of observed calcification. Macroscopic particles were few. In
      contrast, cross-clamping produced substantial numbers of small-size particles.
      These findings emphasize microembolic risks associated with cross-clamping of
      atherosclerotic vessels.

PMID- 21070123
TI  - Tinnitus patients lost to follow-up.
AB  - Tinnitus patients without hearing loss or hyperacusis often start tinnitus
      retraining therapy but do not return to the tinnitus clinic for follow-up visits.
      The aim of this study was to evaluate how these 'missing patients' feel and
      whether they still use their sound generators after they discontinue retraining
      therapy. We interviewed 269 tinnitus patients by phone who never returned to the
      clinic after receiving initial counseling and a generator for sound enrichment.
      Twenty-six percent did not have tinnitus anymore, 30.5% still used the sound
      generator to treat their tinnitus, and 43.5% did not use their sound generator
      but still suffered from tinnitus. This study suggests that therapists need to
      contact missing patients periodically to follow their improvement, encourage
      them, and decide on new therapeutic approaches as necessary.

PMID- 21070124
TI  - Development and analysis of an International Speech Test Signal (ISTS).
AB  - For analysing the processing of speech by a hearing instrument, a standard test
      signal is necessary which allows for reproducible measurement conditions, and
      which features as many of the most relevant properties of natural speech as
      possible, e.g. the average speech spectrum, the modulation spectrum, the
      variation of the fundamental frequency together with its appropriate harmonics,
      and the comodulation in different frequency bands. Existing artificial signals do
      not adequately fulfill these requirements. Moreover, recordings from natural
      speakers represent only one language and are therefore not internationally
      acceptable. For this reason, an International Speech Test Signal (ISTS) was
      developed. It is based on natural recordings but is largely non-intelligible
      because of segmentation and remixing. When using the signal for hearing aid
      measurements, the gain of a device can be described at different percentiles of
      the speech level distribution. The primary intention is to include this test
      signal with a new measurement method for a new hearing aid standard (IEC 60118
      15).

PMID- 21070125
TI  - Eight years of pulmonary valve replacement with a suggestion of a promising
      alternative.
AB  - In a retrospective study we assessed surgical results following right ventricular
      to pulmonary artery connection repair or replacement at a medium of 2.4 years (0
      8) follow-up. Data were retrieved from hospital charts. RESULTS: Three hundred
      and sixty five operations were performed in 286 patients in eight years starting
      in 2000 using different surgical methods. Homografts and Monocusps had a more
      than 50% significantly lower risk for reoperation than Contegra or bicuspid
      valves (p < 0.01). Data for infants and older children and grown ups were
      analysed separately. In the infant group no significant difference between the
      different methods (homograft, Contegra and Monocusp) was detected. In older
      patients, the Perimount valves performed extremely well with no need for
      reoperation after 2.5 years of follow-up. Perimount valves and homografts
      performed better than other solutions (p = 0.01). CONCLUSION: Although the follow
      up for the Perimount valves was short, they are promising and need to be followed
      long-term. The homograft and the Monocusp remain valuable choices.

PMID- 21070126
TI  - A novel BMPR2 gene mutation associated with exercise-induced pulmonary
      hypertension in septal defects.
AB  - OBJECTIVE: Our study aimed to investigate the relationship between exercise
      induced pulmonary arterial hypertension and genetic changes related to the
      transforming growth factor-beta (TGF-beta) signalling pathway in patients with
      cardiac septal defects. DESIGN: In a population-based group of 44 patients (age
      13-25 years) with either isolated ventricular septal defect (n=27) or isolated
      atrial septal defect (n=17), right ventricular systolic pressure response to
      submaximal exercise was studied by echocardiography and classified as normal
      (<=45 mmHg), borderline (45-50 mmHg) or abnormal (>50 mmHg). Three genes related
      to TGF-beta, bone morphogenetic protein receptor type 2 (BMPR2), activin receptor
      like kinase 1 (ALK1) and endoglin (ENG), were analyzed by DNA sequencing (only
      BMPR2) and multiplex ligand-dependent probe amplification (BMPR2, ALK1 and ENG).
      RESULTS: Pressure response was borderline in five and abnormal in nine patients.
      Five patients showed mutations in exon 12 of the bone morphogenetic protein
      receptor type 2 gene. The previously described polymorphism S775N (c. 2324, G >
      A) was found in three patients with normal pressure response. The mutation Y589C
      (c. 1766, A > G), which has not been described previously, was found in two of 14
      patients with borderline/abnormal pressure response. CONCLUSION: Genetic changes
      in the BMPR2 gene may be overrepresented in patients with cardiac septal defects
      and exercise-induced pulmonary hypertension.

PMID- 21070127
TI  - Role of the vascular endothelial growth factor in the inverse relationship
      between increased nuchal translucency thickness and fetomaternal transfusion.
AB  - OBJECTIVE: To elucidate the possible etiological role of the vascular endothelial
      growth factor (VEGF) in the inverse correlation between nuchal translucency (NT)
      thickness and fetomaternal transfusion (FMT). METHODS: The level of FMT was
      determined prospectively in 80 viable, singleton pregnancies in which 10-14-week
      ultrasonographic scanning, NT thickness measurement; chorionic villus sampling
      (CVS) for fetal karyotyping and VEGF concentration determination were performed.
      The grouping procedures were based either on NT thickness (<2 MoM in Group I, and
      >=2 MoM in Group II), or on karyotype (euploid in Group A, and aneuploid in Group
      B). The level of FMT was determined via maternal serum alpha-fetoprotein levels
      before and after CVS. The FMT and the VEGF concentration of the chorionic tissue
      were analysed in comparisons between Groups I and II, and between Groups "A" and
      "B". RESULTS: The mean level of FMT after CVS was 72.5+/-21.3 MUL and 19.28+/-5.4
      MUL in Groups I (n=44) and II (n=36), respectively (P<0.02). The VEGF
      concentration of the chorionic tissue in Groups I and II was 40.6+/-16.7 pg/mg
      protein and 21.1+/-6.3 pg/mg protein, respectively (P=0.28). The mean level of
      FMT was 57.9+/-15.0 MUL and 8.1+/-3.9 MUL in Groups A and B, respectively
      (P<0.003). The VEGF concentration of the chorionic tissue in Groups A and B was
      25.9+/-10.7 pg/mg protein and 21.3+/-11.3 pg/mg protein, respectively (P=0.77).
      CONCLUSION: No difference exists in the VEGF concentration in the aspirated
      chorionic tissue between Groups I and II and between Groups A and B. A higher
      level of FMT was observed among the aneuploid pregnancies after CVS than among
      the euploid cases. Chorionic VEGF does not influence the inverse relationship
      between the pre-CVS NT thickness and FMT.

PMID- 21070128
TI  - Expert recommendations for the diagnosis and treatment of iron-deficiency anemia
      during pregnancy and the postpartum period in the Asia-Pacific region.
AB  - Anemia during pregnancy and the postpartum period is commonly caused by iron
      deficiency and is a significant worldwide issue with severe consequences for both
      mother and developing fetus. From a worldwide perspective, iron-deficiency anemia
      (IDA) during pregnancy is highest in the Asia-Pacific region; however, there has
      been little guidance in this region for safe and effective treatment. An expert
      panel was convened to develop a concise and informative set of recommendations
      for the treatment of IDA in pregnant and postpartum women in the Asia-Pacific
      region. This manuscript provides these recommendations and aims to reduce the
      morbidity and mortality associated with IDA in pregnant and postpartum women in
      the Asia-Pacific region. The consensus recommendations define anemia as a
      hemoglobin (Hb) level <10.5 g/dL during pregnancy and <10 g/dL during the
      postpartum period, and provide cut-off Hb levels to initiate therapy with oral
      iron, intravenous iron or red blood cell transfusion.

PMID- 21070129
TI  - Acceptability of the fetal electrocardiographic (STAN(r)) monitoring system by
      staff at a high-risk maternity unit.

PMID- 21070130
TI  - Weight gain and dietary intake during pregnancy in industrialized countries--a
      systematic review of observational studies.
AB  - BACKGROUND: Gestational weight gain (GWG) above the recently recommended ranges
      is likely to be related to adverse pregnancy outcomes and therefore a challenge
      in industrialized countries. AIMS: We conducted a systematic review on
      observational studies in order to gain more evidence on whether diets with lower
      caloric/protein content or other diets might be associated with lower GWG.
      METHODS: We searched in MEDLINE and EMBASE for observational studies written in
      English or German reporting associations between diet and GWG in singleton
      pregnancies of healthy women in industrialized countries. RESULTS: We identified
      12 studies which met the inclusion criteria. Five studies suggested significant
      positive associations between energy intake and GWG, whereas three found no
      significant association. Further significant positive associations of GWG were
      reported with respect to protein intake, animal lipids, energy density and a
      number of different food servings per day, whereas intake of carbohydrates and
      vegetarian diet were associated with less GWG. CONCLUSIONS: We suggest that GWG
      might be reduced by lower energy intake in pregnancy.

PMID- 21070131
TI  - The world of e-patients: A content analysis of online social networks focusing on
      diseases.
AB  - OBJECTIVE: as the participatory Web developed to create virtual worlds and
      communities, health institutions and activists discovered Web 2.0 tools, in
      particular the creation of health-related online social networks. To analyze the
      existing online social networks dedicated to health issues, we performed an
      active search on the Internet for such Web sites and analyzed their features
      according to the content analysis method. METHODS: the study was performed in
      September and October 2009. We analyzed a sample of health social networks for
      patients, selected using four common search engines. A codebook was elaborated to
      investigate four areas: general information; technical characteristics and
      utilities; characteristics of the Web site and contents, both general and related
      to the online community. RESULTS: the search led to a sample of 41 social
      networks. Twenty-three Web sites (56.1%) were dedicated to several diseases, the
      others to one only. Although the majority of the sample (87.8%) provided a way to
      contact the Web site, only five (12.2%) showed the name of the author or
      operating organization. Eight Web sites (19.5%) indicated one or more sponsors,
      and nine (22.0%) named one or more partners. It was often hard to tell whether an
      institution mentioned was a sponsor or a partner. Five Web sites (12.2%) enabled
      users to buy health-related products online. Twelve Web sites (29.3%) offered
      users the chance to search for doctors, and 12 (29.3%) gave therapeutic
      information. Two Web sites (4.9%) published aggregate statistical data about the
      patients registered with the social network. CONCLUSIONS: the data reveal the
      high heterogeneity of health-related social networks and raise interesting
      considerations on such controversial topics as the quality of online health
      information, research perspectives, interactivity, and empowerment. In
      particular, our findings are relevant to criticism regarding the openness and
      transparency of these Web sites, the use of personal data, and privacy issues.

PMID- 21070132
TI  - A review on remote monitoring technology applied to implantable electronic
      cardiovascular devices.
AB  - Implantable electronic cardiovascular devices (IECD) include a broad spectrum of
      devices that have the ability to maintain rhythm, provide cardiac
      resynchronization therapy, and/or prevent sudden cardiac death. The incidence of
      bradyarrhythmias and other cardiac problems led to a broader use of IECD, which
      turned traditional follow-up into an extremely heavy burden for healthcare
      systems to support. Our aim was to assess the impact of remote monitoring on the
      follow-up of patients with IECD. We performed a review through PubMed using a
      specific query. The paper selection process included a three-step approach in
      which title, abstract, and cross-references were analyzed. Studies were then
      selected using previously defined inclusion criteria and analyzed according to
      the country of origin of the study, year, and journal of publication; type of
      study; and main issues covered. Twenty articles were included in this review.
      Eighty percent of the selected papers addressed clinical issues, from which 94%
      referred clinical events identification, clinical stability, time savings, or
      physician satisfaction as advantages, whereas 38% referred disadvantages that
      included both legal and technical issues. Forty-five percent of the papers
      referred patient issues, from which 89% presented advantages, focusing on patient
      acceptance/satisfaction, and patient time-savings. The main downsides were
      technical issues but patient privacy was also addressed. All the papers dealing
      with economic issues (20%) referred both advantages and disadvantages equally.
      Remote monitoring is presently a safe technology, widely accepted by patients and
      physicians, for its convenience, reassurance, and diagnostic potential. This
      review summarizes the principles of remote IECD monitoring presenting the current
      state-of-the-art. Patient safety and device interaction, applicability of current
      technology, and limitations of remote IECD monitoring are also addressed. The use
      of remote monitor should consider the selection of patients, the type of disease,
      and centers' availability to receive, interpret and respond to device alerts.
      Before remote IECD monitoring can be routinely used, technical, procedure, and
      ethical/legal issues should be addressed.

PMID- 21070133
TI  - Speech timing and pausing in children with specific language impairment.
AB  - Articulation rate, speaking rate, as well as the duration and location of pauses,
      were analysed in 10 children with specific language impairment (SLI) and a
      comparison group of seven younger children producing utterances of similar
      lengths. Children with SLI were significantly slower in articulation rate, but
      not speaking rate or pausing time, indicating a group difference attributable to
      longer syllable duration. The correlation between the duration of the pause
      preceding a child's speaking turn and the length of the subsequent child
      utterance was calculated as an indication of children's use of the pause for
      planning the utterance. The correlation was not significant in either group, and
      not significantly different between groups. An analysis of the position of pauses
      within speaking turns showed more syllables following than preceding the pause,
      with no significant group differences. Theoretical implications are discussed.

PMID- 21070135
TI  - Vowel confusion patterns in adults during initial 4 years of implant use.
AB  - This study investigated adult cochlear implant users' (n = 39) vowel recognition
      and confusions by an open-set syllable test during 4 years of implant use, in a
      prospective repeated-measures design. Subjects' responses were coded for phoneme
      errors and estimated by the generalized mixed model. Improvement in overall vowel
      recognition was highest during the first 6 months, showing statistically
      significant change until 4 years, especially for the mediocre performers. The
      best performers improved statistically significantly until 18 months. The poorest
      performers improved until 12 months and exhibited more vowel confusions. No
      differences were found in overall vowel recognition between Nucleus24M/24R and
      Med-ElC40+ device users (matched comparison), but certain vowels showed
      statistically significant differences. Vowel confusions between adjacent vowels
      were evident, probably due to the implant users' inability to discriminate
      formant frequencies. Vowel confusions were also dominated by vowels whose average
      F1 and/or F2 frequencies were higher than the target vowel, indicating a
      basalward shift in the confusions.

PMID- 21070136
TI  - Proximal and distal. Rethinking linguistic form and use for clinical purposes.
AB  - With clinical purposes in mind, a review of the proximal/distal opposition is
      carried out in order to define a universal parameter of variability in semiotic
      procedures. By taking into consideration different-although notionally inter
      related-senses of the proximal/distal opposition, a cluster of semiotic
      properties is proposed, which initially permits one to characterize dimensions of
      variability in the form and use of gestures. The subsequent and central aim of
      this paper is, however, to demonstrate that the same, or homologous, properties
      can also serve to characterize variability in the use of language, by assuming a
      basic connection between gesturing and linguistic behaviour. The main focus of
      interest and the starting point for reflections are communicative impairments as
      manifested in apraxia and aphasia.

PMID- 21070138
TI  - Cognitive decrements do not follow neuromuscular alterations during passive heat
      exposure.
AB  - To investigate what triggers cognitive and neuromuscular alterations during
      passive heat exposure, eight volunteers performed simple (One Touch Stockings of
      Cambridge, OTS-4) and complex (OTS-6) cognitive tasks as well as neuromuscular
      testing (maximal isometric voluntary contractions of the thumb with electrical
      stimulation of the motor nerve and magnetic stimulation of the motor cortex).
      These tests were performed at the start (T1), after 1 h 30 min (T2), 3 h (T3) and
      4 h 30 min (T4) of exposure in both hot (HOT) (Wet Bulb Globe Temperature [WBGT]
      = 38 degrees  +/- 1.4 degrees C) and neutral control (CON) (WBGT = 19 degrees  +/
      0.3 degrees C) environments. Environmental temperatures were adjusted during the
      HOT session to induce target core temperatures (T(core)) (T1 ~ 37.3 degrees ; T2
      ~ 37.8 degrees ; T3 ~ 38.3 degrees ; T4 ~ 38.8 degrees C). At T1 and T4 the OTS-6
      was lower in HOT than in CON in response to the rapid increase in skin
      temperature and to hyperthermia, respectively. In HOT, the increase in T(core)
      limited force production capacity possibly via alterations occurring upstream the
      motor cortex (from T(core) ~ 37.8 degrees C) but also via a decrement in motor
      cortical excitability (from T(core) ~ 38.3 degrees C). These alterations in
      cortex excitability failed to explain the cognitive alterations that can
      originate from an additional cognitive load imposed by temperature variations.

PMID- 21070137
TI  - Alterations in cognitive performance during passive hyperthermia are task
      dependent.
AB  - The objectives of this study were to (1) assess the effect of passive heating
      upon attention and memory task performance, and (2) evaluate the effectiveness of
      the application of cold packs to the head on preserving these functions. Using a
      counter-balance design 16 subjects underwent three trials: a control (CON, 20
      degrees C, 40% rH), hot (HOT, 50 degrees C, 50% rH) and hot with the head kept
      cool (HHC). In each condition, three attention tests and two memory tests were
      performed. Mean core, forehead and tympanic temperatures were all significantly
      higher (p < 0.05) during HOT (38.6 degrees  +/-0.1 degrees , 39.6 degrees  +/-
      0.2 degrees  and 38.8 degrees +/-0.1 degrees C, respectively) and HHC (38 degrees
      +/- 0.2, 37.7 degrees  +/- 0.3 degrees  and 37.7 degrees C, respectively) than
      in CON (37.1 degrees  +/- 0.6 degrees , 33.3 degrees  +/- 0.2 degrees  and 35.9
      degrees  +/- 0.3 degrees C, respectively). Results indicate that there was
      impairment in working memory with heat exposure (p < 0.05) without alteration in
      attentional processes. The regular application of cold packs only prevented the
      detrimental effect of hyperthermia on short-term memory. Our results show that
      impairments in cognitive function with passive hyperthermia and the beneficial
      effect of head cooling are task dependent and suggests that exposure to a hot
      environment is a competing variable to the cognitive processes.

PMID- 21070139
TI  - Hyperthermia enhances the effect of beta-lapachone to cause gammaH2AX formations
      and cell death in human osteosarcoma cells.
AB  - PURPOSE: The anti-cancer effect of beta-lapachone (beta-lap) is positively
      related to the cellular activity of NAD(P)H:quinone oxidoreductase (NQO1). Heat
      shock has been reported to elevate cellular NQO1. The effect of heating on the
      NQO1 expression in human osteosarcoma cells (HOS) and the response of the cells
      to the combined treatment with beta-lap and hyperthermia was investigated.
      MATERIALS AND METHODS: The effects of beta-lap alone, hyperthermia alone and in
      combination to cause clonogenic death and apoptosis in HOS cells were elucidated.
      The effect of heating on the NQO1 expression was evaluated with western blot
      analysis. The effect of beta-lap on the cell cycle distribution was elucidated
      with flow cytometry and to cause DNA damage was determined by assessing the
      gammaH2AX foci formation. RESULTS: Treatment of HOS cells with beta-lap at 42
      degrees C was markedly more effective than that at 37 degrees C in causing
      clonogenic cell death. Heating caused a long-lasting up-regulation of NQO1 in the
      cells, and sensitised the cells to beta-lap. The gammaH2AX foci formation was
      increased immediately after beta-lap treatment and preheating increased the beta
      lap-induced gammaH2AX foci formation. CONCLUSIONS: The sensitivity of HOS cells
      to beta-lap was increased not only during heating but also after heating as
      demonstrated by the increase in the clonogenic cell death and gammaH2AX foci
      formation. The increase in beta-lap sensitivity after heating appeared to be due
      to the heat-induced elevation of NQO1 activity.

PMID- 21070140
TI  - Improved hyperthermia treatment control using SAR/temperature simulation and PRFS
      magnetic resonance thermal imaging.
AB  - PURPOSE: This article explores the feasibility of using coupled electromagnetic
      and thermodynamic simulations to improve planning and control of hyperthermia
      treatments for cancer. The study investigates the usefulness of preplanning to
      improve heat localisation in tumour targets in treatments monitored with PRFS
      based magnetic resonance thermal imaging (MRTI). METHODS: Heating capabilities of
      a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator
      were investigated with electromagnetic and thermal simulations of SAR in
      homogeneous phantom models and two human leg sarcomas. High frequency structure
      simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR
      patterns were coupled into EPhysics (Ansoft) for thermal modelling with
      temperature-dependent variable perfusion. Simulations were accelerated by
      integrating tumour-specific anatomy into a pre-gridded whole body tissue model.
      To validate this treatment planning approach, simulations were compared with MR
      thermal images in both homogenous phantoms and heterogeneous tumours. RESULTS:
      SAR simulations demonstrated excellent agreement with temperature rise
      distributions obtained with MR thermal imaging in homogeneous phantoms and
      clinical treatments of large soft-tissue sarcomas. The results demonstrate
      feasibility of preplanning appropriate relative phases of antennas for localising
      heat in tumour. CONCLUSIONS: Advances in the accuracy of computer simulation and
      non-invasive thermometry via MR thermal imaging have provided powerful new tools
      for optimisation of clinical hyperthermia treatments. Simulations agree well with
      MR thermal images in both homogeneous tissue models and patients with lower leg
      tumours. This work demonstrates that better quality hyperthermia treatments
      should be possible when simplified hybrid model simulations are performed
      routinely as part of the clinical pretreatment plan.

PMID- 21070141
TI  - Elevated influenza-related excess mortality in South African elderly individuals,
      1998-2005.
AB  - BACKGROUND: Although essential to guide control measures, published estimates of
      influenza-related seasonal mortality for low- and middle-income countries are
      few. We aimed to compare influenza-related mortality among individuals aged >=65
      years in South Africa and the United States. METHODS: We estimated influenza
      related excess mortality due to all causes, pneumonia and influenza, and other
      influenza-associated diagnoses from monthly age-specific mortality data for 1998
      2005 using a Serfling regression model. We controlled for between-country
      differences in population age structure and nondemographic factors (baseline
      mortality and coding practices) by generating age-standardized estimates and by
      estimating the percentage excess mortality attributable to influenza. RESULTS:
      Age-standardized excess mortality rates were higher in South Africa than in the
      United States: 545 versus 133 deaths per 100,000 population for all causes
      (P<.001) and 63 vs 21 deaths per 100,000 population for pneumonia and influenza
      (P=.03). Standardization for nondemographic factors decreased but did not
      eliminate between-country differences; for example, the mean percentage of winter
      deaths attributable to influenza was 16% in South Africa and 6% in the United
      States (P<.001). For all respiratory causes, cerebrovascular disease, and
      diabetes, age-standardized excess death rates were 4-8-fold greater in South
      Africa than in the United States, and the percentage increase in winter deaths
      attributable to influenza was 2-4-fold higher. CONCLUSIONS: These data suggest
      that the impact of seasonal influenza on mortality among elderly individuals may
      be substantially higher in an African setting, compared with in the United
      States, and highlight the potential for influenza vaccination programs to
      decrease mortality.

PMID- 21070142
TI  - Dose-dependent risk of neutropenia after 7-day courses of artesunate monotherapy
      in Cambodian patients with acute Plasmodium falciparum malaria.
AB  - BACKGROUND: Fears of emerging artemisinin resistance in western Cambodia have
      prompted a series of clinical trials investigating whether slow responses to
      antimalarial treatment can be overcome by increasing doses of drug. METHODS:
      Patients with uncomplicated malaria were allocated 1 of 3 oral artesunate
      monotherapy regimens (2, 4, or 6 mg/kg/day for 7 days) and were observed for 42
      days. A series of safety measures, including complete blood count on days 0, 3,
      6, and 14, was implemented because of a lack of safety data for these
      experimental doses. RESULTS: After 3 doses, geometric mean absolute neutrophil
      counts were reduced in all groups, and 2 patients required artesunate to be
      discontinued because of neutropenia (absolute neutrophil count, <1.0 * 10(3)
      cells/MUL). Recipients of the 6 mg/kg/day dosage had significantly lower
      geometric mean absolute neutrophil counts than did recipients of the 2 and 4
      mg/kg/day dosages at 6 and 14 days (P < .001 for each). Overall, 5 (19%) of 26
      patients who received the 6 mg/kg/day dosage became neutropenic within 14 days,
      triggering a cohort-halting rule and ending the trial early. Pharmacokinetic data
      from neutropenic patients showed wide variance, with plasma clearance occurring
      significantly slower in neutropenic patients than in nonneutropenic patients.
      CONCLUSIONS: Artesunate remains a crucial drug for the treatment of malaria, and
      determining optimal dosing regimens is vital to overcome emerging resistant
      parasite strains along the Thai-Cambodian border. However, future experimental
      dosing studies must be designed with care, because the safety of such regimens
      can no longer be assumed. The artemisinin derivatives remain one of the safest
      classes of antimalarial drugs, but this study demonstrates that the dosing limit
      may have been reached.

PMID- 21070143
TI  - Evaluation of the pharmacokinetics and metabolism of a novel histone deacetylase
      inhibitor, KBH-A40, in rats.
AB  - The pharmacokinetics and metabolism of KBH-A40, a novel delta-lactam-based
      histone deacetylase inhibitor, were characterized in male Sprague-Dawley rats.
      KBH-A40 exhibited a high clearance (12.0 +/- 2.8 l h-1kg-1), a large volume of
      distribution at steady state, V(ss) (3.9 +/- 1.5 l kg-1), and a short half-life,
      t1/2 (2.0 +/- 0.3 h). KBH-A40 was rapidly converted to its metabolite, KBH-A40
      carboxylate, after intravenous (2 and 20 mg kg-1 and oral (10 mg kg-1)
      administration; the carboxylate metabolite remained at elevated concentrations in
      the plasma for more than 8 h. Glucuronide conjugate of KBH-A40 was identified
      qualitatively by using liquid chromatography tandem mass spectrometry in rat
      plasma. KBH-A40 was rapidly absorbed (t(max) = 0.4 h) after oral dose, consistent
      with its permeability in Caco-2 cells. Its oral bioavailability was low (14.2
      14.8%). An apparent "double peak" phenomenon was observed for both KBH-A40 and
      KBH-A40 carboxylate after oral administration. KBH-A40 was degraded rapidly by
      glucuronidation, but not by cytochrome P450-mediated oxidation, in rat liver
      microsomes. These results suggest that the rapid metabolism of KBH-A40 could be a
      major reason for its poor pharmacokinetics. Therefore, this work provides
      valuable structural information to improve pharmacokinetic properties of KBH-A40,
      a lead compound.

PMID- 21070144
TI  - Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats
      with liver cirrhosis and diabetes mellitus, alone and in combination.
AB  - Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in
      humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and
      in combination (LCD) did not seem to be reported. Sildenafil was administered
      intravenously (10 mg/kg) and orally (20 mg/kg) to control, LC, DM, and LCD rats.
      Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM,
      and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were
      significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In
      LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and
      2030%, respectively) than controls. In LC, DM, and LCD rats, significantly
      greater AUCs of intravenous sildenafil were due to the slower hepatic extraction
      of sildenafil (because of decrease in the protein expression of hepatic CYP2C11
      and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats,
      greater magnitude of increase in AUCs of oral sildenafil than those after the
      intravenous administration could be mainly due to the decrease in the intestinal
      extraction of sildenafil (because of decrease in the protein expression of
      intestinal CYP2C11 in LC and LCD rats).

PMID- 21070150
TI  - Value of C-reactive protein after neurosurgery: a prospective study.
AB  - AIM: The aim of this manuscript is to review the current state of knowledge
      regarding C-reactive protein (CRP) kinetics after standard neurosurgical
      procedures, and to determine the value of CRP as a screening test for early post
      operative infectious complications as opposed to other more commonly used tests,
      and as a marker of peri-operative surgical insult. METHODS: Over 18 months
      period, CRP levels, alongside with ESR and WCC were assessed pre-operatively (at
      day 0) and post-operatively (at days 1,2,3,4 and 5) in 50 consecutive female
      patients and 50 consecutive male patients undergoing seven neurosurgical
      procedures. Each of the seven procedures involved a different level of intra
      operative trauma. Factors of possible influences on CRP, including volume of
      blood transfused intra-operatively, type of anaesthetic administered, use of anti
      inflammatory drugs and antibiotics levels were recorded. RESULTS: The median age
      of our study population was 29.1 (mean +/- SD: 28.4 +/- 10.2; range: 20.4-53.8).
      Of the 100 patients recruited for our study, 13 developed post-operative
      infectious complications. In these patients, a secondary CRP rise or failure to
      decrease as expected had sensitivity, specificity, negative and positive
      predictive value of 100%, 93.1%, 100% and 68.4%, respectively, for detecting
      infectious complications. The mean post-operative CRP levels were highest in the
      most surgically traumatic procedure--lobotomy for epilepsy intervention, and
      lowest in the least surgically traumatic procedure--stereotactic brain biopsy (p
      < 0.001). Volume of blood transfused intra-operatively, type of anaesthetic
      administered, use of anti-inflammatory drugs and antibiotics levels did not
      affect CRP kinetics. CONCLUSION: The results of this study suggest that CRP is a
      more reliable screening test for post-operative infectious complications in the
      practice of neurosurgery than other more commonly used tests (WCC and ESR).
      Furthermore, the results suggest that peak post-operative CRP levels mirrors the
      level of incurred intra-operative surgical insult.

PMID- 21070145
TI  - Identification of phase-I metabolites and chronic toxicity study of the Kv1.3
      blocker PAP-1 (5-(4-phenoxybutoxy)psoralen) in the rat.
AB  - 1. PAP-1 (5-(4-phenoxybutoxy)psoralen), a potent small-molecule blocker of the
      voltage-gated potassium Kv1.3 channel, is currently in preclinical development
      for psoriasis. This study was undertaken to identify the major phase I
      metabolites of PAP-1 in Sprague-Dawley (SD) rats. 2. Five phase I metabolites,
      that is 5-(oxybutyric-acid)psoralen (M1), 5-[4-(4-hydroxybutoxy)]psoralen (M2), 5
      [4-(4-hydroxyphenoxy)butoxy]psoralen (M3), 5-[4-(3-hydroxyphenoxy)butoxy]psoralen
      (M4), and 8-hydroxyl-5-(4-phenoxybutoxy)psoralen (M5), were isolated from the
      bile of rats and identified by mass spectrometry and NMR spectroscopy. The last
      four metabolites are new compounds. 3. Incubation of PAP-1 with SD rat liver
      microsomes rendered the same five major metabolites in a nicotinamide adenine
      dinucleotide phosphate (NADPH)-dependent manner suggesting that cytochrome P450
      (CYP) enzymes are involved in PAP-1 metabolism. Inhibitors of rat CYP1A1/2 (alpha
      naphthoflavone) and CYP3A (ketoconazole) but not CYP2D6 (quinidine), CYP2E
      (diethyldithiocarbamate), or CYP2C9 (sulphaphenazole) blocked the metabolism of
      PAP-1 in rat microsomes. 4. Of the five metabolites M3, M4, and M5 were found to
      inhibit Kv1.3 currents with nanomolar IC50s, while M1 and M2 were inactive. Our
      results identified the Kv1.3-inactive M1 as the major phase I metabolite, and
      suggest that hydroxylation and O-dealkylation are the major pathways of PAP-1
      metabolism. 5. We further conducted a 6-month repeat-dose toxicity study with PAP
      1 at 50 mg/kg in both male and female Lewis rats and did not observe any toxic
      effects.

PMID- 21070151
TI  - Preservation of facial nerve function after resection of vestibular schwannoma.
AB  - OBJECTIVE: Most data regarding facial nerve function in patients undergoing
      microsurgical resection of vestibular schwannomas predominantly include series
      performed at a single institution. In an effort to minimise individual surgeon or
      institutional bias, we performed an analysis of the published literature on
      facial nerve outcomes following microsurgical resection of vestibular
      schwannomas. The objective of this study was to provide a comprehensive
      assessment of reported outcomes for facial nerve preservation after VS surgery.
      MATERIALS AND METHODS: We identified a total of 296 studies involving over 25,000
      patients that included outcome data for facial nerve function of vestibular
      schwannoma patients treated surgically. Data regarding surgical approach, tumour
      size, patient age, and use of intra-operative monitoring were extracted and
      correlated with facial nerve function after surgery. Patients with preoperative
      facial nerve dysfunction (House-Brackmann score 3 or higher) were excluded and
      'facial nerve preservation' was defined as grade I or II House-Brackmann function
      at last follow-up visit. RESULTS: A total of 79 articles reporting on 11,873
      patients met our inclusion criteria contributing to our analysis. Patients
      treated with the middle cranial fossa approach had a trend towards higher overall
      facial nerve preservation rate (85%), compared to the translabyrinthine approach
      (81%, p = 0.07) , and did statistically better than the retrosigmoid approach
      (78%, p < 0.0001). Patients with an average tumour size <20 mm had significantly
      improved facial nerve preservation rates, compared to larger tumours (90% vs.
      67%, p < 0.0001). Patients under 65 years of age had a lower facial nerve
      preservation rate (71% vs. 84%, p < 0.001). Finally, the use of intra-operative
      monitoring improved the facial nerve preservation rate (76% vs. 71%, p < 0.001).
      CONCLUSION: Factors that appear to be associated with facial nerve preservation
      after microsurgical resection of a vestibular schwannoma include tumour size <20
      mm, use of the middle fossa approach and use of neuromonitoring during surgery.
      These data provide a summary assessment of the published literature regarding
      facial nerve preservation after microsurgical resection of vestibular schwannoma.

PMID- 21070152
TI  - Management of cerebral venous thrombosis in a patient with Lane-Hamilton syndrome
      and coeliac disease, epilepsy and cerebral calcification syndrome.
AB  - We describe a case of cerebral venous thrombosis presenting in a patient with
      Lane-Hamilton syndrome and coeliac disease epilepsy cerebral calcification
      syndrome. This is a first reported occurrence of this combination. Delayed
      anticoagulation with early external ventricular drain insertion for life
      threatening raised intracranial pressure resulted in a successful outcome.

PMID- 21070153
TI  - Mesial temporal lobe epidermoid tumour compressing the hippocampal formation
      caused refractory temporal lobe epilepsy.
AB  - The authors report an unusual case of intradural epidermoid tumour in a 19-year
      old girl presenting with refractory complex partial seizures including auditory
      hallucinations, and memory dysfunction. A complete resection was carried out
      sparing the hippocampus resulting in seizure freedom.

PMID- 21070154
TI  - Acute foramen magnum syndrome from acquired Chiari I malformation relieved by
      ventriculoperitoneal shunt revision.
AB  - An adult case of shunt malfunction presenting with acute quadriparesis as a
      manifestation of foramen magnum syndrome with acquired Chiari type I malformation
      is described in this study. The corticospinal function was restored after shunt
      revision. MRI showing considerable ascent of cerebellar tonsils after surgery is
      shown. Theories regarding the formation of acquired Chiari I malformations,
      alongside the possible synergistic roles of intracranial pathologies and
      cerebrospinal fluid drainage in the development of this entity are discussed.

PMID- 21070155
TI  - Atypical teratoid/rhabdoid tumour of the central nervous system in adult: case
      report.
AB  - Atypical teratoid/rhabdoid tumours (AT/RT) are aggressive neoplasms of the
      central nervous system occurring mainly in the paediatric population. We reported
      a 32-year-old male patient who was admitted in emergency in unconscious state.
      The neoplasm was localised in the left frontal region and was totally excised.
      The histological and immunohistochemical report revealed AT/RT. This unusual
      presentation underlines the necessity of considering this devastating neoplasm in
      the differential diagnosis of malignant brain tumours of adults.

PMID- 21070156
TI  - Intracanalicular epidermoid cyst. A case report.
AB  - We describe the presentation and management of a rare case of an epidermoid cyst
      located within canal of the left internal acoustic meatus, lying entirely within
      the petrous part of the temporal bone. The patient underwent surgery by an
      extended middle fossa approach and a total excision of a cyst containing cheesy,
      pearly white, avascular material was achieved. Neuroradiology provides a
      diagnosis with reasonable accuracy and an appropriate surgical approach can be
      planned for the excision of the tumour.

PMID- 21070157
TI  - Response to "La maladie de Grisel treated by combined C1-2 transarticular and C1
      lateral mass screw fixation".

PMID- 21070158
TI  - Double insurance redux.

PMID- 21070159
TI  - Pitfalls in cerebrospinal fluid spectroscopy results for the diagnosis of
      subarachnoid haemorrhage.

PMID- 21070160
TI  - CSF spectroscopy and hyperbilirubinaemia.

PMID- 21070162
TI  - Mitochondria with tubulovesicular cristae in renal oncocytomas.
AB  - Renal oncocytoma and chromophobe renal cell carcinoma (CRCC) are closely related
      tumors. They are considered the extremes of a spectrum with several variants.
      Ultrastructural examination of the mitochondria is a helpful procedure in the
      diagnosis of these neoplasms. Renal oncocytomas show mitochondria with piled
      lamellar cristae, and CRCC exhibited mitochondria with tubulovesicular cristae.
      In a series of 23 histologically diagnosed renal oncocytomas examined by electron
      microscopy, the authors found 5 tumors exhibiting more cells with mitochondria
      showing tubulovesicular cristae. The authors believe these 5 cases present a
      submicroscopic appearance intermediate between renal oncocytoma and CRCC,
      although with benign clinical behavior.

PMID- 21070163
TI  - Microvillous inclusion disease: a clinicopathologic study of 17 cases from the
      UK.
AB  - BACKGROUND: Microvillous inclusion disease (MVID) is a rare congenital disease
      producing intractable secretory diarrhea in early infancy. It is characterized by
      diffuse intestinal villous atrophy with no inflammatory reaction. Ultrastructural
      identification of apical microvillous inclusions in the surface enterocytes is
      diagnostic. However, there is difficulty in the diagnosis of MVID due to the
      existence of variants (e.g., microvillous dystrophy), possible disease
      resolution, and tissue orientation for electron microscopy (EM). The authors
      analyzed materials from 4 patients with MVID from a single institution. The
      morphologic features, distribution of lesions, biomarkers, and complementary
      ultrastructural characteristics were studied. DESIGN: Materials of MVID cases
      were collected from 6 different hospitals in the United Kingdom between 1990 and
      2008. Epidemiological data, including age range, median, mode, sex ratios, and
      follow-up, were retrieved. All intestinal biopsy specimens were analyzed
      histologically, histochemically (for PAS, n = 17), immunohistochemically (for
      CD10, n = 2 and polyclonal CEA, n = 4), and ultrastructurally (n = 9). RESULTS:
      Ultrastructurally, apical microvillous inclusions in surface enterocytes in
      duodenal biopsies were identified in all cases, while 1 case had variant
      morphology (microvillous dystrophy and very occasionally atypical microvillous
      inclusions). Tissue orientation for EM was supportive for identification of
      inclusions in apical enterocytes. Morphologically, a bubbly vacuolated appearance
      of the apical cytoplasm with extensive or patchy absence of the brush border with
      occasional cytoplasm inclusions was observed in the enterocytes. Some of these
      changes vaguely resembled gastric mucin cell metaplasia. Architecturally, villous
      blunting with either crypt hypoplasia or hyperplasia and absence of inflammation
      were common findings. The epithelial changes were also found in colon biopsies.
      PAS, CD10, and p-CEA showed a bright apical cytoplasmic blush/staining, which
      correlated ultrastructurally with apical granules with inclusions of variable
      electron density in all cases. These stains also highlighted the targetoid
      inclusions. CONCLUSION: Besides electron microscopy identification of inclusions,
      the light microscopic morphological features together with the biomarker studies
      highlighting the apical cytoplasmic blush are quite unique and diagnostic of
      MVID. Furthermore, it is the opinion of the authors that a diagnosis of MVID can
      be made without electron microscopy.

PMID- 21070164
TI  - Electron microscopic findings in skin biopsies from patients with Danon disease.
AB  - Danon disease is a rare lysosomal disorder. It is due to deficiency of lysosomal
      associated protein-2. In human LAMP-2 gene is located at chromosome region Xq24.
      Danon disease is characterized by hypertrophic cardiomyopathy, skeletal myopathy,
      mental retardation and retinopathy. To date, the morphological characterization
      of Danon disease has been limited to endomyocardial and skeletal muscle biopsies.
      In the current study we demonstrated that electron microscopy of a more
      accessible tissue, skin biopsies, is a useful method in the diagnosis of Danon
      disease.

PMID- 21070165
TI  - Mucinous colorectal adenocarcinoma with signet-ring cells: immunohistochemical
      and ultrastructural study.
AB  - A primary mucinous colorectal adenocarcinoma tissue with signet-ring cells, as
      revealed after histological evaluation, was examined ultrastructurally. The
      authors also analyzed the immunohistochemical data of the tissue for serotonin,
      vasoactive intestinal polypeptide (VIP), bombesin, somatostatin, and glucagon,
      using the peroxidase anti-peroxidase (PAP) method and the immunogold labeling
      method for light and electron microscope, respectively. Electron microscopically
      mucinous adenocarcinoma was characterized by the formation of small lumen.
      Adenocarcinoma cells were full of mucous granules of varying electron density,
      providing a good environment for the tumor cells to grow. They also exhibited a
      significant loss of microvilli and intracytoplasmic junctions, which could allow
      the cells to disseminate. Signet-ring cells were located in the basal site of the
      ducts or in the lamina propria and appeared neoplastic, with mucin accumulation
      intracellularly and an eccentric crescent-shaped nucleus. The cytoplasmic
      organelles were decreased and at the periphery of the cell. The PAP method
      demonstrated that these cells were strongly positive for bombesin and also
      positive for vasointestinal polypeptide (VIP). The immunogold method detected
      bombesin immunoreactivity in the vacuoles as well as in other cytoplasmic
      membranes, whereas VIP was localized mainly in the plasma membrane. The location
      of signet-ring cells combined with the immunoreactivity for bombesin and VIP
      indicated that signet-ring cells were of neuroendocrine origin and probably
      dedifferentiated enterochromaffin-like endocrine cells. These findings have
      implications for understanding the biological behavior of these composite
      malignant tumors and could help in the knowledge of the origin of signet-ring
      cells.

PMID- 21070166
TI  - Nanobacteria and psammoma bodies: ultrastructural observations in a case of
      pathological placental calcification.
AB  - Nanobacteria are controversial infectious agents with nanometric size, the
      capacity to nucleate hydroxyapatite and grow in culture, and present in human
      diseases associated with calcification and psammoma bodies. The authors report a
      case of pathological placental calcifications associated with nanobacteria.
      Electron microscopy and electron energy loss spectroscopy imaging were used to
      recognize 160-nm-sized calcium-free bodies mainly presenting as extracellular
      fibrillary tangles and 500-nm-sized calcified bodies; they encrusted the syncito
      trophoblast basal membrane and aggregated into miniaturized psammoma bodies.
      Nanobacteria may be composed of a prionoid protein with self-assembling and self
      propagating abilities whose growth is associated with the formation of psammoma
      bodies.

PMID- 21070167
TI  - Ultrastructural characteristics (or evaluation) of Creutzfeldt-Jakob disease and
      other human transmissible spongiform encephalopathies or prion diseases.
AB  - The authors report on a large series of human prion diseases to establish
      ultrastructural characteristics that may be useful for their diagnosis. For
      Creutzfeldt-Jakob disease (CJD and its variant, vCJD) and fatal familial insomnia
      (FFI) only vacuolation (spongiform change) and the presence of tubulovesicular
      structures are consistent findings. Other changes, such as the presence of
      myelinated vacuoles, branching cisternae, neuroaxonal dystrophy, and autophagic
      vacuoles, were present in different proportions in either CJD or FFI, but they
      are nonspecific ultrastructural findings that can also occur in other
      neurodegenerative conditions. The hallmark of Gerstmann-Straussler-Scheinker
      disease (GSS) and vCJD is the amyloid plaque, but plaques of GSS and kuru are
      different than those of vCJD. Whereas the former are typical unicentric kuru type
      or multicentric plaques, the latter are unicentric florid plaques. Also, kuru
      plaques are nonneuritic, whereas GSS florid plaques are usually neuritic;
      however, a proportion of plaques from GSS was also found to have nonneuritic
      characteristics. Thus, the presence or absence of dystrophic neurites is not a
      discriminatory factor for GSS and vCJD. Furthermore, plaques from GSS with
      different mutations were also slightly different. In GSS with mutations P102L,
      232T, and A117V plaques were stellate while in 1 case with 144 base-pair
      insertion and in GSS-A117V, round plaques were also observed, and typical
      primitive neuritic plaques, i.e., composed of dystrophic neurites with little or
      no amyloid, were found only in a P102L case from the original Austrian family. In
      2 cases of sporadic CJD, the kuru stellate plaque predominated.

PMID- 21070168
TI  - Hepatocellular calcification in severe ischemia-reperfusion injury in a liver
      allograft.
AB  - Ischemia-reperfusion injury (IR) of solid organ allografts is a consequence of
      ischemia resulting from disruption of blood flow during organ harvest and
      transportation. Histologically, this manifests as variable necrosis in a pattern
      similar to that seen in systemic hypoperfusion. Calcification of hepatocytes has
      been rarely observed in ischemic injury due to systemic shock and in two cases of
      severe IR, both of which were associated with graft loss and death. The authors
      present another case of dystrophic calcification within hepatocytes occurring in
      a liver allograft affected by severe IR. Biochemical stains revealed that the
      mineralized material was calcium phosphate (likely hydroxyapatite). By electron
      microscopy, the hepatocyte cytoplasm was filled with variably calcified vacuoles,
      a subset of which likely represented swollen mitochondria. When encountered in
      hepatic allograft biopsies, hepatocellular calcification is associated with
      ischemic injury and a poor prognosis.

PMID- 21070169
TI  - Fibrohistiocytic tumors containing zebra body-like inclusions and fibripositors.
AB  - Plexiform fibrohistiocytic tumor (PFH) and cellular neurothekeoma (CN) are dermal
      neoplasms that present many histological and immunophenotype similarities as well
      as unknown histogenesis. Recently, the ultrastructural detection of zebra body
      like inclusions in lesional histiocytes has been considered crucial to favor the
      diagnosis of PFH over that of CN. Here we report two examples of dermal tumors
      that were diagnosed as CN. Electron microscopy revealed cytoplasmic collections
      of myelin and zebra body-like inclusions in tumor cells; these inclusions focally
      merged together or with multivesicular bodies; tumor cells also showed collagen
      secretion granules and fibripositors, i.e., channels containing single, double or
      multiple copies of collagen fibrils. These observations support the view that PFH
      and CN have a common histogenesis and consists of cells sharing phagocityc and
      fibrillogenic abilities.

PMID- 21070170
TI  - Influence of food on recruitment pattern in the termite, Microcerotermes
      fuscotibialis.
AB  - Recruitment pattern in the termite, Microcerotermes fuscotibialis Sjostedt
      (Isoptera: Termitidae) was found to be largely influenced by the presence or
      absence of food. This is reflected in the quantitative recruitment that occurred
      after food had been detected by the scouting foragers. Results showed that this
      information was communicated and responded to by other confederates in the nest
      within four to seven minutes after food addition or removal. The presence of an
      additional food source relative to an already existing one did not have any
      significant impact on the recruitment activities of this termite. Recruitment
      decision pattern in M. fuscotibialis involve to a large extent an "autocratic"
      decision strategy in the development and maintenance of recruitment process in
      this termite species.

PMID- 21070172
TI  - Maximizing oviposition efficiency when mass rearing the coccinellid,
      Sasajiscymnus tsugae, a predator of the hemlock woolly Adelgid, Adelges tsugae.
AB  - Sasajiscymnus tsugae Sasaji and McClure (Coleeptera: Coccinellidae), is a
      biological control agent imported for management of hemlock woolly adelgid,
      Adelges tsugae Annand. In mass rearing S. tsugae, accurate estimation of egg
      numbers is important because larvae are cannibalistic, especially at higher
      densities. To determine the most accurate means of estimating egg production,
      three brands of gauze were compared as oviposition substrates. Curad(r) gauze
      provided the most accurate estimate of egg production, and was the most cost
      effective brand. When eggs were collected from oviposition jars, similar adult
      yields of S. tsugae occurred between rearing cages infested with 1,650 eggs from
      gauze compared to eggs on the twigs from within these jars. Additionally,
      orientation of oviposition jars impacted S. tsugae egg production as
      significantly more eggs were produced in horizontally oriented oviposition jars.

PMID- 21070171
TI  - Amplified fragment length polymorphism mapping of quantitative trait loci for
      economically important traits in the silkworm, Bombyx mori.
AB  - Cocoon related characteristics are economically important traits in the silkworm,
      Bombyx mori L. (Lepidoptera: Bombycidae). In this study a genetic linkage map was
      developed that identified QTL controlling the cocoon weight, cocoon shell weight,
      and cocoon shell percentage using 161 amplified fragment length polymorphism
      (AFLP) markers. Twenty PstI/TaqI primer combinations were employed to genotype 78
      F(2) progenies derived from a cross between P107 Japanese inbred line and
      Khorasan Lemon Iranian native strain. Among polymorphic markers, 159 AFLP markers
      were assigned to 24 linkage groups at the LOD threshold of 2.5 that varied in
      length from 4 to 299 cM. The total length of the linkage map was 2747 cM, giving
      an average marker resolution of 19.31 cM. A total of 21 AFLP markers were
      identified that were distributed over the ten linkage groups linked to the three
      studied traits using the composite interval mapping method. The explained
      variation rate by QTL controlling cocoon weight, cocoon shell weight, and cocoon
      shell percentage ranged from 0.02% to 64.85%, 0.2% to 49.11%, and 0.04% to
      84.20%, respectively. These QTL controlled by different actions as well as under
      dominance, additive, partial dominance, dominance, and over dominance.

PMID- 21070173
TI  - Nutritional indices of the cotton bollworm, Helicoverpa armigera, on 13 soybean
      varieties.
AB  - The effects of 13 soybean varieties (356, M4, M7, M9, Clark, Sahar, JK, BP,
      Williams, L17, Zane, Gorgan3, and DPX) on nutritional indices of the cotton
      bollworm, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae), were determined
      at 25 +/- 1 degrees  C, 65 +/- 5% RH and a photoperiod of 16:8 L:D. Fourth instar
      larvae reared on Zane showed the highest efficiency of conversion of digested
      food (ECD) and approximate digestibility (AD) values (0.299 and 0.867,
      respectively) compared with other varieties. The lowest value of ECD and food
      consumed (FC) was on 356 (0.133 and 53.82 mg, respectively). The highest and
      lowest efficiency of conversion of ingested food (ECI) of fifth instar larvae
      (0.235 and 0.156, respectively) were on Zane and M4, respectively. The ECI and
      ECD values of whole larval instars were the highest on M7 (0.524 and 0.820,
      respectively) and lowest on Sahar (0.279 and 0.353, respectively). However, the
      highest and lowest value of consumption index (CI) was on M7 (7.351) and BP
      (3.462). Among the different varieties of soybean, the highest AD value was on M9
      (0.858), and the lowest was on Zane (0.597). The results indicated that M4,
      Sahar, and JK were partially resistant to H. armigera.

PMID- 21070174
TI  - Uninvited guests: traditional insect repellents in Estonia used against the
      clothes moth Tineola bisselliella, human flea Pulex irritons and bedbug Cimex
      lectularius.
AB  - Extensive folklore records from pre-modern Estonia give us an excellent
      opportunity to study a variety of local plant knowledge and plant use among the
      peasantry in various parts of the country. One important biocultural domain where
      plant knowledge has been crucial was in the various methods of combating
      different ectoparasites that cohabited and coexisted with humans and their
      domestic animals. Some of these methods were widely known (world-wide, Eurasia,
      Europe, Baltic Rim), while others were more local. Here we discuss ways of
      reducing clothes moths Tineola bisselliella (Hummel) (Lepidoptera: Tineidae),
      human fleas Pulex irritons L. (Siphonaptera: Pulicidae) and bedbugs Cimex
      lectularius L. (Hemiptera: Cimicidae) with the help of plants. Various taxa used
      as traditional repellents have been identified. The use of plants as repellents
      and their toxic principles are also discussed from a comparative perspective.

PMID- 21070175
TI  - Prey preference of the predatory mite, Amblyseius swirskii between first instar
      western flower thrips Frankliniella occidentalis and nymphs of the twospotted
      spider mite Tetranychus urticae.
AB  - The prey preference of polyphagous predators plays an important role in
      suppressing different species of pest insects. In this study the prey preference
      of the predatory mite, Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae)
      was examined between nymphs of the twospotted spider mite, Tetranychus urticae
      Koch (Acari: Tetranychidae) and first instar larvae of the western flower thrips,
      Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), as well as
      between active and chrysalis spider mite protonymphs and active and chrysalis
      spider mite deutonymphs. The study was done in the laboratory on bean leaf discs
      at 25 +/- 1 degrees  C and 70 +/- 5% RH. Amblyseius swirskii had a clear
      preference for thrips compared to both spider mite protonymphs and deutonymphs.
      About twice as many thrips as spider mites were consumed. Amblyseius swirskii did
      not show a preference between active and chrysalis stages of spider mites.

PMID- 21070176
TI  - Identification and expression analysis of minichromosome maintenance proteins in
      the silkworm, Bombyx mori.
AB  - The minichromosome maintenance protein (MCM) family is involved in the regulatory
      role of DNA replication in eukaryotic organisms. A cDNA encoding of an MCM of the
      silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), was cloned by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and sequenced. The resultant
      amino acid sequence and phylogenetic analysis revealed high identity to MCM, and
      specifically to MCM7, of vertebrates and invertebrates. An RT-PCR showed that the
      bmMCM7 transcript was present in the ovaries, testes, silk glands, and fat bodies
      of larval silkworms. Expression plasmids were transformed into competent
      Escherichia coli and overexpressed. This is the first report on the
      identification of MCM helicase of the silkworm, B. mori.

PMID- 21070178
TI  - A constraint condition for foraging strategy in subterranean termites.
AB  - Previous studies have explored the relationship between termite branch tunnel
      geometry and foraging efficiency in a model simulation in which foraging
      efficiency, gamma, for two termite species, Coptotermes formosanus Shiraki and
      Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae), was investigated in
      response to two variables, the probability of tunnel branching (P(branch)) and
      the probability of tunnel branch termination (Pterm). It was found that simulated
      tunnel patterns based on empirical data did not have maximum foraging efficiency.
      We hypothesized that termites could increase their foraging efficiency in
      response to landscape heterogeneity. The present study investigated how termites
      could control the two variables, P(branch) and P(term), in response to the
      external environment in terms of tunnel network connectivity. It was found that
      the best simulated strategy for C. formosanus and R. flavipes termites would
      occur if both P(branch) and P(term) were increased together. This study provides
      possible mechanisms for foraging strategies in subterranean termites and a
      baseline for future empirical work.

PMID- 21070177
TI  - Increased fluctuating asymmetry in a naturally occurring hybrid zone between the
      stick insects Bacillus rossius rossius and Bacillus rossius redtenbacheri.
AB  - The impact of interracial hybridization on fluctuating asymmetry (FA) and
      phenotypic variability (sigma(2)p) in a presumed natural hybrid zone between the
      stick insects, Bacillus rossius rossius Rossi and Bacillus rossius redtenbacheri
      Nasceti & Bullini (Phasmatodea: Bacillidea), found on the Italian island Sardinia
      was investigated. The lengths of three bilateral traits and three unilateral
      traits were measured, and each individual was genotyped by five microsatellite
      loci. The genotypic data clearly confirmed the existence of the hybrid zone on
      Sardinia. A significantly increased FA was found in the hybrids when compared to
      both parental subspecies, which this study attributes to genetic
      incompatibilities in the hybrids. The increase in FA was not correlated with any
      increase in sigma(2)P in the hybrids, which indicates that in this case sigma(2)p
      and FA originate from separate processes.

PMID- 21070179
TI  - Observation of the peach fruit moth, Carposina sasakii, larvae in young apple
      fruit by dedicated micro-magnetic resonance imaging.
AB  - Infestation of young apple fruits by the larvae of the peach fruit moth,
      Carposina sasakii Matsumura (Lepidoptera: Carposinidae), was studied by a small
      dedicated micro-magnetic resonance imaging (MRI) apparatus using the three
      dimensional (3D) gradient-echo method and the two-dimensional (2D) and 3D spin
      echo methods. Changes from a young larva at 1.8 mm in length to a mature one
      ready to leave the fruit were observed in relation to the progression of
      infestation of the fruit tissues. The trace of larva intrusion was demonstrated
      by a series of sliced images in the 3D image data of an infested fruit, where it
      entered from outside the calyx, and migrated to near the vasculature around the
      carpel through the core. The small, dedicated MRI device was proven useful for
      ecological studies of the growth and movement of insect larvae in their food
      fruits. It can also be applied to detect the infestation of small fruits by
      insect larvae.

PMID- 21070180
TI  - Comparison of three optical tracking systems in a  complex navigation scenario.
AB  - Three-dimensional rotational X-ray imaging with the SIREMOBIL Iso-C3D (Siemens
      AG, Medical Solutions, Erlangen, Germany) has become a well-established intra
      operative imaging modality. In combination with a tracking system, the Iso-C3D
      provides inherently registered image volumes ready for direct navigation. This is
      achieved by means of a pre-calibration procedure. The aim of this study was to
      investigate the influence of the tracking system used on the overall navigation
      accuracy of direct Iso-C3D navigation. Three models of tracking system were used
      in the study: Two Optotrak 3020s, a Polaris P4 and a Polaris Spectra system, with
      both Polaris systems being in the passive operation mode. The evaluation was
      carried out at two different sites using two Iso-C3D devices. To measure the
      navigation accuracy, a number of phantom experiments were conducted using an
      acrylic phantom equipped with titanium spheres. After scanning, a special pointer
      was used to pinpoint these markers. The difference between the digitized and
      navigated positions served as the accuracy measure. Up to 20 phantom scans were
      performed for each tracking system. The average accuracy measured was 0.86 mm and
      0.96 mm for the two Optotrak 3020 systems, 1.15 mm for the Polaris P4, and 1.04
      mm for the Polaris Spectra system. For the Polaris systems a higher maximal error
      was found, but all three systems yielded similar minimal errors. On average, all
      tracking systems used in this study could deliver similar navigation accuracy.
      The passive Polaris system showed - as expected - higher maximal errors; however,
      depending on the application constraints, this might be negligible.

PMID- 21070181
TI  - Application of a new dosimetry program TAOCS to assess transient vapour
      absorption in the upper airways.
AB  - Most previous models of vapour absorption in the respiratory tract have assumed
      steady state flow fields and steady state diffusion into the airway walls.
      However, recent studies have shown that transient absorption flux into the walls
      of the upper airways can significantly influence predicted uptake or deposition
      values. The disadvantage of accounting for transient absorption into the airway
      walls is a more complex boundary condition and numerical model. The objective of
      this study was to evaluate the effects of both transient flow fields and
      transient mass absorption on the uptake of highly and moderately soluble
      compounds in an upper airway model. The geometry consisted of the mouth-throat
      region coupled with a multilayer wall model containing air, mucus, tissue, and
      blood phases. Based on previous studies, a boundary condition that represents
      transient absorption into the airway walls was applied. A new dosimetry program,
      named transient absorption of chemical species (TAOCS) 1.0, was developed and
      implemented to determine the coefficients needed for the transient boundary
      condition expression and to apply the boundary condition to the computational
      fluid dynamics (CFD) model. Both steady state and transient conditions were
      considered for the airflow field and wall absorption. The case of perfect wall
      absorption with a zero surface concentration was also considered. Results
      indicated that steady state airflow provided a reasonable approximation to
      transient airflow conditions in terms of total and local deposition (values
      within 10-30%). However, the simulation of transient wall absorption was critical
      unless the compound was highly soluble (with a mucus-air partition coefficient
      >=320), in which case a perfect absorption boundary condition was accurate to
      within a relative difference of 50%. Still, the perfect absorption boundary
      condition did not accurately capture local deposition enhancement factor values.
      Based on these findings, implementation of the transient absorption boundary
      condition appears critical to predict local deposition characteristics for even
      highly soluble compounds. Use of the TAOCS program simplified the implementation
      of the complex transient absorption condition making the CFD simulation process
      more efficient and user-friendly.

PMID- 21070182
TI  - Association of angiotensin-1-converting enzyme gene variations with silicosis
      predisposition.
AB  - Interactions between several genes and environmental factors occur in silicosis
      and other dust-mediated pulmonary fibrosis. It has been suggested that several
      genes play role in individual susceptibility to silicosis. The aim of this study
      was to determine the angiotensin-1-converting enzyme (ACE) gene (I/D) variations
      in patients with silicosis and healthy controls in Iranian Kurdish population.
      Forty-one male workers with silicosis and 41 healthy male controls were entered
      in the study. Polymerase chain reaction (PCR) method was carried out for allele
      and genotype typing. Our finding showed that the frequencies of D and I alleles
      were 0.65 and 0.35 in the silicotic patients compared to 0.52 and 0.48 in the
      controls. The frequencies of ACE D/D, D/I, and I/I genotypes were 15 (36.59%), 23
      (56.1%), and 3 (7.31%) in patients, and 14 (34.15%), 15 (36.59%), and 12 (29.27%)
      in the controls, respectively. The results indicate that the frequency of ACE
      D/D+D/I genotypes were higher in the patients group (92.7% vs. 70.73%) (OR: 5.24,
      95% CI: 1.35-20.30, P = 0.01). Also, ACE I/I genotype frequency was lower in
      patients (7.32% vs. 29.27%) (OR: 0.19, 95% CI: 0.04-0.73, P = 0.01). It can be
      concluded that ACE D/D and I/D genotypes may play a role in the susceptibility to
      silicosis; on the contrary, ACE I/I genotype may have protective effect.

PMID- 21070183
TI  - Inhalation carcinogenicity and toxicity of 1,2-dichloropropane in rats.
AB  - The toxicity and carcinogenicity of 1,2-dichloropropane (DCP) were examined by
      inhalation exposure of male and female F344 rats to DCP for either 13 wk or 2
      years. In the 13-wk study, the DCP concentrations used were 125, 250, 500, 1000,
      or 2000 ppm (v/v), and in the 2-year study the DCP concentrations were 80, 200,
      or 500 ppm (v/v). Thirteen-week exposure to DCP induced hyperplasia in the
      respiratory epithelium and atrophy of the olfactory epithelium at 125 ppm and
      above. At the higher levels of exposure, hemolytic anemia and lesions of liver
      and adrenal gland were observed. Two-year exposure to DCP significantly increased
      incidences of papilloma in the nasal cavity of male and female rats exposed to
      500 ppm DCP. In addition, three cases of esthesioneuroepithelioma were observed
      in the DCP-exposed male rats. Total nasal tumors increased in a concentration
      dependent manner. Hyperplasia of the transitional epithelium and squamous cell
      hyperplasia, both of which were morphologically different from the hyperplasia of
      the respiratory epithelium observed in the 13-wk exposure study, occurred in a
      concentration-dependent manner; these lesions are considered to be preneoplastic
      lesions. Atrophy of the olfactory epithelium, inflammation of the respiratory
      epithelium, and squamous cell metaplasia were also seen in the 2-year study.
      These results demonstrate that DCP is a nasal carcinogen in rats. Lifetime cancer
      risks for humans exposed to DCP in the ambient air and work environment were
      quantitatively estimated, using both nonthreshold and threshold approaches, with
      the data obtained from the 2-year study.

PMID- 21070184
TI  - Asian dust and titanium dioxide particles-induced inflammation and oxidative DNA
      damage in C57BL/6 mice.
AB  - Inhaled particulate matter (PM) might influence many adverse health effects in
      human body, including increased exacerbations of pulmonary and cardiovascular
      diseases. In this study, we examined the associations between PM and pulmonary
      adverse effects. Two types of particles, Asian dust (AD) and titanium dioxide
      (TiO(2)), were administered intratracheally to C57BL/6 mice. The mice were
      exposed to saline and saline suspensions of 20 mg/kg of AD, TiO(2) particles
      twice a week for 12 weeks. Following exposure with these particles, the lungs
      were analyzed histopathologically by hematoxylin and eosin (H&E) and Masson's
      trichrome (MT) staining. Oxidative injuries were determined by
      immunohistochemistry (IHC) for 8-oxoguanine in the lungs and Comet assays in
      peripheral blood mononuclear cells (PBMCs) of C57BL/6 mice. Mice exposed to AD
      and TiO(2) showed significant inflammatory changes and oxidative damages in the
      lungs as compared with the control group. DNA damage in PBMCs was also increased
      significantly in AD and TiO(2)-exposed mice. However, lung fibrosis was minimal
      and there was no significant difference between PM exposed and control mice.
      Exposure to AD and TiO(2) particles-induced similar inflammatory damages in the
      lungs and elicited oxidative DNA damage in the PBMCs.

PMID- 21070185
TI  - Caffeine induced psychotic exacerbation.

PMID- 21070186
TI  - Subjective well-being mediates the effects of resilience and mastery on
      depression and anxiety in a large community sample of young and middle-aged
      adults.
AB  - OBJECTIVE: The tripartite model of depression and anxiety hypothesizes that
      positive and negative affect is related to depression and anxiety. However, the
      specific role of cognitive or psychological well-being constructs like resilience
      and mastery within a tripartite context and throughout adulthood is unclear.
      METHOD: Data was drawn from two longitudinal population-based cohorts, aged 20-24
      and 40-44 based in Canberra, Australia (N = 3989). We sought to determine the
      interrelatedness of two affective measures of subjective well-being, positive and
      negative affect, with two cognitive measures of psychological well-being,
      resilience and mastery. We then tested their independent effects on depression
      and anxiety, and hypothesized, following the tripartite model, that subjective
      well-being would mediate the effects of the psychological well-being variables on
      mental health and that the psychological well-being variables would be more
      strongly related to positive subjective well-being. RESULTS: Principal axis
      factoring delineated four affective and cognitive dimensions of well-being
      comprising positive and negative affect, resilience and mastery. Structural
      equation models identified the psychological well-being variables as
      significantly related to subjective well-being, which fully mediated the effects
      of resilience and partially mediated the effect of mastery on depression and
      anxiety. These findings were consistent throughout both young and middle
      adulthood. CONCLUSIONS: Psychological well-being components are significant
      predictors of subjective well-being affect states that increase vulnerability to
      depression and anxiety.

PMID- 21070187
TI  - Physiological and molecular characterization of atypical lipid-dependent
      Malassezia yeasts from a dog with skin lesions: adaptation to a new host?
AB  - Three lipid-dependent Malassezia isolates (here named 114A, 114B and 114C)
      recovered from a dog with skin lesions were phenotypically and genotypically
      characterized. All presented ovoid cells and buds formed on a narrow base. Most
      of the results from physiological tests were consistent with those of Malassezia
      furfur. The phylogenetic analysis of ITS-1 and LSU nucleotide sequences was
      concordant in placing all three clinical Malassezia isolates close to M. furfur.
      However, the phylogenetic data on the chs-2 sequence revealed that clinical
      isolate 114A is distinct from M. furfur and was closely affiliated to the
      sequence of M. pachydermatis with high nodal support. In particular, lipid
      dependent isolates 114A displayed chs-2 sequences similar (100%) to that of the
      non-lipid dependent species Malassezia pachydermatis. The presence of the genetic
      and physiological polymorphisms detected in these three isolates of M. furfur
      could have resulted from a process of adaptation of this anthropophilic species
      to a new host.

PMID- 21070188
TI  - Relationship separation and mental health problems: findings from a 30-year
      longitudinal study.
AB  - OBJECTIVE: To examine the associations between relationship separation and a
      range of mental health problems including depression, anxiety disorders, alcohol
      abuse/dependence, cannabis abuse/dependence, and total number of mental health
      problems. METHOD: Data were drawn from a 30-year longitudinal study of a birth
      cohort of individuals born in Christchurch, New Zealand. Associations between
      separation and mental health problems were examined using two types of regression
      models: population-averaged generalized estimating equation models and fixed
      effects models. Associations were adjusted for a wide range of fixed and time
      dynamic potential covariate factors. RESULTS: After due allowance was made for
      confounding, separation was associated with depression, suicidal behaviour, and
      the total number of mental health problems (rate ratios range 1.7-3.4, median
      3.2). These associations were apparent both when separation was used as the
      dependent variable and when the mental health problems were used as the dependent
      variables. In contrast, separation was not significantly associated with anxiety
      disorders, alcohol abuse/dependence, or illicit drug abuse/dependence when due
      allowance was made for confounding. Associations between separation and mental
      health problems were not significantly different for men and women. CONCLUSIONS:
      Separation of a cohabiting relationship is associated with increased rates of
      depression, suicidal behaviour, and total mental health problems. However, it was
      not possible to determine the causal direction of the relationship between
      separation and mental health problems. Future studies may need to employ
      approaches other than observational research designs in order to address issues
      of causality.

PMID- 21070189
TI  - Emerging therapeutic targets and agents for glioblastoma therapy--part II.

PMID- 21070190
TI  - Conditional expression of the FTO gene product in rat INS-1 cells reveals its
      rapid turnover and a role in the profile of glucose-induced insulin secretion.
AB  - Common polymorphisms within the FTO (fat mass and obesity-associated) gene
      correlate with increased BMI (body mass index) and a rising risk of Type 2
      diabetes. FTO is highly expressed in the brain but has also been detected in
      peripheral tissues, including the endocrine pancreas, although its function there
      is unclear. The aim of the present study was to investigate the role of FTO
      protein in pancreatic beta-cells using a conditional expression system developed
      in INS-1 cells. INS-1 cells were stably transfected with FTO-HA (haemagluttinin)
      incorporated under the control of a tetracycline-inducible promoter. Induction of
      FTO protein resulted in localization of the tagged protein to the nucleus. The
      level of FTO-HA protein achieved in transfected cells was tightly regulated, and
      experiments with selective inhibitors revealed that FTO-HA is rapidly degraded
      via the ubiquitin/proteasome pathway. The nuclear localization was not altered by
      proteasome inhibitors, although following treatment with PYR-41, an inhibitor of
      ubiquitination, some of the protein adopted a perinuclear localization.
      Unexpectedly, modestly increased expression of FTO-HA selectively enhanced the
      first phase of insulin secretion when INS-1 monolayers or pseudoislets were
      stimulated with 20 mM glucose, whereas the second phase remained unchanged. The
      mechanism responsible for the potentiation of glucose-induced insulin secretion
      is unclear; however, further experiments revealed that it did not involve an
      increase in insulin biosynthesis or any changes in STAT3 (signal transducer and
      activator of transcription 3) expression. Taken together, these results suggest
      that the FTO protein may play a hitherto unrecognized role in the control of
      first-phase insulin secretion in pancreatic beta-cells.

PMID- 21070191
TI  - A brain-derived MeCP2 complex supports a role for MeCP2 in RNA processing.
AB  - Mutations in MECP2 (methyl-CpG-binding protein 2) are linked to the severe
      postnatal neurodevelopmental disorder RTT (Rett syndrome). MeCP2 was originally
      characterized as a transcriptional repressor that preferentially bound methylated
      DNA; however, recent results indicate MeCP2 is a multifunctional protein. MeCP2
      binding is now associated with certain expressed genes and involved in nuclear
      organization as well, indicating that its gene regulatory function is context
      dependent. In addition, MeCP2 is proposed to regulate mRNA splicing and a mouse
      model for RTT shows aberrant mRNA splicing. To further understand MeCP2 and
      potential roles in RTT pathogenesis, we have employed a biochemical approach to
      identify the MeCP2 protein complexes present in the mammalian brain. We show that
      MeCP2 exists in at least four biochemically distinct pools in the brain and
      characterize one novel brain-derived MeCP2 complex that contains the splicing
      factor Prpf3 (pre-mRNA processing factor 3). MeCP2 directly interacts with Prpf3
      in vitro and in vivo and many MECP2 RTT truncations disrupt the MeCP2-Prpf3
      complex. In addition, MeCP2 and Prpf3 associate in vivo with mRNAs from genes
      known to be expressed when their promoters are associated with MeCP2. These
      results support a role for MeCP2 in mRNA biogenesis and suggest an additional
      mechanism for RTT pathophysiology.

PMID- 21070192
TI  - Accuracy of diagnostic tests in multiple sclerosis--a systematic review.
AB  - New diagnostic criteria for multiple sclerosis (MS) have been recently proposed
      and further updates are upcoming. This systematic literature review summarizes
      diagnostic studies in suspected MS to clarify the value of diagnostic tests. We
      included studies of at least 40 patients followed up for 2 years. All studies are
      limited by the fact that no gold standard to validate diagnostic tests is
      available. A second relapse is used as a surrogate in relapsing-remitting MS, but
      long follow-up of at least 5 years is necessary to detect all cases. Many studies
      showed selection bias, partly because of the vague definition of a clinically
      isolated syndrome. Based on these limitations, sensitivity of magnetic resonance
      imaging (MRI) criteria was between 35% and 100%, and specificity was between 36%
      and 92%. Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities
      between 69% and 91% with specificities between 59% and 94%. Combination studies
      of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%).
      Studies on evoked potentials did not justify conclusions about their value. A
      combination of simplified MRI criteria with CSF might be the best approach for an
      early MS diagnosis. However, the value of a very early diagnosis stays
      questionable as patients' benefit of new diagnostic criteria has never been
      addressed.

PMID- 21070193
TI  - The effect of Assertive Community Treatment in Japan.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of the Assertive
      Community Treatment (ACT) program in a Japanese mental health service setting.
      METHOD: This study was a randomized controlled trial. ACT was the intervention
      condition (n = 59), and the usual hospital-based rehabilitation program was the
      control condition (n = 59). Outcome indicators include in-patient days,
      psychiatric symptoms, social functioning, quality of life, and client
      satisfaction. The follow-up period was 12 months after the intervention. RESULTS:
      We found a significant reduction of in-patient days for the ACT group
      demonstrated by t-test (t = 2.33, P = 0.02). However, the results of ancova did
      not show significant differences for in-patient days between the two groups (F =
      1.85, P = 0.18). The depression score for Brief Psychiatric Rating Scale for the
      ACT group was significantly lower than the control group at the 12-month follow
      up assessment (F = 5.57, P = 0.03). According to the t-test, the ACT group had a
      higher client satisfaction than the control group (t = 2.08, P = 0.05).
      CONCLUSION: We concluded that ACT had a positive influence, as evidenced by a
      reduction of in-patient days, lower depressive symptoms, and higher client
      satisfaction.

PMID- 21070194
TI  - Challenges and opportunities in advancing models of care for older adults: an
      assessment of the National Institute on Aging research portfolio.
AB  - OBJECTIVES: To identify existing projects supported by the National Institute on
      Aging (NIA) that may relate to the recommendations for models of care (MOCs)
      presented in the 2008 Institute of Medicine Report, Retooling for an Aging
      America: Building the Healthcare Workforce. DESIGN: Cross-sectional analysis of
      NIA's grant portfolio. SETTING: NIA. PARTICIPANTS: NIA grantees. MEASUREMENTS:
      NIA's grant portfolio was queried for the period 1999 to 2008 using a variety of
      search terms related to MOCs. Inclusion criteria were adherence to guiding
      principles for MOCs (comprehensive care, efficient care, older person as an
      active partner) or focus on innovative feature(s) of MOCs (interdisciplinary
      care, care management, chronic disease self-management, pharmaceutical
      management, preventive home visits, proactive rehabilitation, transitional care).
      Exclusion criteria were lack of focus on an intervention and focus on informal
      caregivers. Expert NIA staff reviewed and validated projects. RESULTS: One
      hundred thirty-five grants were identified. These grants represent fewer than 1%
      of the approximate number of grants NIA has funded over this same period of time
      (~24,000 grants). Forty-four percent focused on components of comprehensive care
      and 34% on active involvement of older adults. Approximately half specifically
      focused on innovative features of MOCs, ranging from chronic disease self
      management (32%) and proactive rehabilitation (26%) to preventive home visits
      (1%) and transitional care (1%). The majority of projects were investigator
      initiated grants (46%). CONCLUSION: NIA has supported the development of many
      interventions that include components of MOCs related to recommendations from the
      IOM report. The challenge for the future will be determining which of the many
      components of comprehensive care systems are most effective for which subsets of
      the elderly population and assessing opportunities for enhanced collaboration
      between public and private aging research stakeholders.

PMID- 21070196
TI  - Review of Web-Based Module to Train and Assess Competency in Systems-Based
      Practice.
AB  - This module has a goal of increasing learners' understanding of the care
      transitions process through an online, interactive interface that can be
      completed in approximately 30 minutes. The teaching is case-based, using a
      hypothetical patient to walk learners through the main elements that the author
      is emphasizing: highlighting the importance of communication during the discharge
      process, including the preparation of complete discharge summaries; explaining
      the sources of payment for elderly patients moving through the healthcare system;
      and discharge sites according to type and amount of therapy that patients can
      expect to receive.

PMID- 21070195
TI  - Physical and mental health of homebound older adults: an overlooked population.
AB  - There are currently more than 38.9 million people aged 65 an older in the United
      States. Up to 3.6 million of these people are considered housebound and in need
      of home-based care. Although homebound status is not defined specifically, with a
      broad range of disability levels, it is evident that people who are homebound
      suffer from a multitude of medical and psychiatric illnesses. This review
      examines the current literature to identify the specific physical and psychiatric
      factors most responsible for older adults becoming and remaining housebound.
      Homebound older adults suffer from metabolic, cardiovascular, cerebrovascular,
      and musculoskeletal diseases, as well as from cognitive impairment, dementia, and
      depression, at higher rates than the general elderly population. The information
      in this review will explain the specific types of care the homebound population
      needs and discuss the care that could help ease their suffering and delay their
      entry into a nursing home or hospital.

PMID- 21070197
TI  - A randomized clinical trial on preventing pressure ulcers with wheelchair seat
      cushions.
AB  - OBJECTIVES: To determine the efficacy of skin protection wheelchair seat cushions
      in preventing pressure ulcers in the elderly nursing home population. DESIGN:
      Clinical trial with participants assigned at random to a skin protection or
      segmented foam cushion. Two hundred thirty-two participants were recruited
      between June 2004 and May 2008 and followed for 6 months or until pressure ulcer
      incidence. SETTING: Twelve nursing homes. PARTICIPANTS: Nursing home residents
      aged 65 and older who were using wheelchairs for 6 or more hours per day and had
      a Braden score of 18 or less and a combined Braden activity and mobility score of
      5 or less. Participants were recruited from a referred sample. INTERVENTION: All
      participants were provided with a fitted wheelchair and randomized into skin
      protection (SPC, n=113) or segmented foam (SFC, n=119) cushion groups. The SPC
      group received an air, viscous fluid and foam, or gel and foam cushion. The SFC
      group received a 7.6-cm crosscut foam cushion. MEASUREMENTS: Pressure ulcer
      incidence over 6 months for wounds near the ischial tuberosities (IT ulcers) were
      measured. Secondary analysis was performed on combined IT ulcers and ulcers over
      the sacrum and coccyx (sacral ulcers). RESULTS: One hundred eighty participants
      reached a study end point, and 42 were lost to follow-up. Ten did not receive the
      intervention. There were eight (6.7%) IT ulcers in the SFC group and one (0.9%)
      in the SPC group (P=.04). There were 21 (17.6%) combined IT and sacral ulcers in
      the SFC group and 12 (10.6%) in the SPC group (P=.14). CONCLUSION: Skin
      protection cushions used with fitted wheelchairs lower pressure ulcer incidence
      for elderly nursing home residents and should be used to help prevent pressure
      ulcers.

PMID- 21070198
TI  - Association of primary cutaneous amyloidosis with atopic dermatitis: a nationwide
      population-based study in Taiwan.
AB  - BACKGROUND: Primary cutaneous amyloidosis (PCA) is a pruritic skin disorder most
      commonly seen in Southeast Asia and South America. Association of PCA with atopic
      dermatitis (AD) has been reported in the literature. However, no large-scale
      epidemiological study of PCA and its associations with other diseases has been
      conducted so far. OBJECTIVES: We aimed to provide overall demographic data and
      comorbidities of patients with PCA based on a nationwide database in Taiwan.
      METHODS: Cases of PCA were collected from records of National Health Insurance
      claims from 2000 to 2007. We analysed patients' gender, age when the diagnosis
      was first made, and the overall 8-year prevalence. We also investigated
      comorbidities. RESULTS: The overall 8-year prevalence of PCA was 7.87 per 10,000
      persons. Although there was no significant gender difference in the prevalence of
      PCA, men and women showed a different peak age (men, 71-80 years; women, 41-50
      years) and a different age distribution at diagnosis. The mean age at diagnosis
      of PCA was significantly younger for women than for men. Men sought medical
      assistance for PCA more frequently than women. There was a higher disease
      activity from May to September than during other months. PCA was strongly
      associated with AD (odds ratio 7.18). Patients with PCA had a higher comorbidity
      of hyperlipidaemia and diabetes mellitus. CONCLUSIONS: This is the first
      nationwide population-based epidemiological study of PCA. We demonstrate that PCA
      can be associated with other disorders, especially AD.

PMID- 21070199
TI  - Clinical, power Doppler sonography and histological assessment of the psoriatic
      plaque: short-term monitoring in patients treated with etanercept.
AB  - BACKGROUND: To date, the diagnosis of psoriasis is based on both clinical history
      and physical examination, and its severity is assessed by the Psoriasis Area and
      Severity Index (PASI). Continuous technological advances in the field of
      sonography have led to the development of equipment with high power Doppler
      frequency, which allows for very detailed morphological information regarding the
      dermal blood flow. OBJECTIVES: To compare power Doppler sonography (PDS) with
      clinical and histological findings before and after etanercept treatment in
      patients with psoriasis. METHODS: Twelve patients with a clinical diagnosis of
      psoriasis were enrolled in this study. The PASI, PDS and histological
      examinations were assessed in all patients on the same day at baseline, and after
      12 weeks of biological treatment. PDS examination was performed by an experienced
      sonographer, using a sonographic system equipped with transducer ranging from 6
      to 18 MHz and Doppler frequency ranging from 7 to 14 MHz. RESULTS: At follow up
      there was a significant decrease in PASI. A significant change was also detected
      for the PDS findings (P = 0.005). At baseline the median value for factor VIII
      staining was 1.5, and the median value for vascular endothelial growth factor
      (VEGF) staining was also 1.5. At follow up there was a significant decrease in
      both factor VIII and VEGF staining scores. Moreover, a positive correlation
      between reduction in PDS score and improvement in clinical and histological
      scores was found: Spearman's rho = 0.639, P = 0.0022; Spearman's rho = 0.619, P =
      0.0013; Spearman's rho = 0.765, P = 0.0002, respectively. CONCLUSIONS: Our
      results show a significant correlation between PDS findings and both PASI and
      histological degree of vascularization before and after etanercept treatment.
      These data provide evidence in favour of the validity of PDS in the assessment of
      dermal perfusional changes in patients with psoriatic plaques.

PMID- 21070200
TI  - Gardner-Diamond syndrome: a rare differential diagnosis of child abuse.

PMID- 21070201
TI  - Polo-like kinase 1 (Plk1) in cutaneous T-cell lymphoma.
AB  - BACKGROUND: Polo-like kinase 1 (Plk1) has multiple functions throughout mitosis.
      Plk1 levels are high in a number of cancers and haematological malignancies while
      being low in most differentiated tissues. OBJECTIVES: To assess the
      immunoreactivity of Plk1 in cutaneous T-cell lymphoma (CTCL) as a potential
      therapeutic target, to differentiate Plk1 levels among lesion types and to
      compare the detection level of Plk1 in fresh frozen (f) vs. paraffin-embedded (p)
      tissue. METHODS: Immunohistochemical staining of CTCL skin lesions with anti-Plk1
      antibody was performed in a total of 65 biopsies from 49 patients with CTCL. Both
      f and p tissue was available for comparison in 46 biopsies. RESULTS: Tumour-stage
      CTCL lesions displayed significantly more Plk1 (mean f 7.7%, p 8.8%) than patch
      (mean f 0.7%, p 2.0%) and plaque-stage lesions (mean f 1.1%, p 2.0%) (P < 0.05).
      Plk1 ranged from 0% to 18% in f and 0% to 24% in p samples. p tissue revealed a
      higher mean Plk1 detection rate of 4.4% compared with 2.9% in f tissue with no
      statistical significance. CONCLUSIONS: Our results indicate that in CTCL, Plk1 is
      increased mainly in advanced lesions. Several Plk1 inhibitors have already shown
      promising results in preclinical and clinical phase I and II trials for different
      types of cancers with low adverse effects. Immunohistochemical detection of high
      Plk1 levels in patients with CTCL could help select individuals who might benefit
      from treatment with small molecule Plk1 inhibitors.

PMID- 21070202
TI  - Depletion of antigen-presenting cells by clodronate liposomes reverses the
      psoriatic skin phenotype in KC-Tie2 mice.
AB  - BACKGROUND: There is ongoing debate regarding the initiation of psoriatic plaque
      as primarily arising from an anomaly in epidermal keratinocytes (KCs) or from
      abnormalities in immunocytes that secondarily activate otherwise normal KCs. In
      mice engineered to overexpress the angiopoietin receptor Tie2 in KCs, skin
      spontaneously develops the characteristic clinical, histological and immune cell
      phenotypes of psoriasis which can be reversed with either transgene repression or
      ciclosporin administration, suggesting key roles for both KCs and T cells in
      mediating the skin disease in this murine model. OBJECTIVES: To determine if
      antigen-presenting cells (APCs) and macrophages alone are sufficient to sustain
      psoriasiform inflammation in the KC-Tie2 murine model of psoriasis. METHODS:
      Clodronate liposomes were intradermally injected into involved dorsal skin of KC
      Tie2 or control animals once a week for 6weeks and acanthosis, angiogenesis,
      immune cell infiltration and cytokine production were quantitated using
      immunohistochemistry and interactive image analyses, enzyme-linked immunosorbent
      assay (ELISAs) and quantitative real-time polymerase chain reaction (qRT-PCR).
      RESULTS: Clodronate liposome injection eliminated CD11c+, F4/80+ and CD11b+ cells
      in the skin and returned CD8+ T-cell numbers to control mouse levels. APC
      depletion in KC-Tie2 mouse skin resulted in resolution of the acanthotic skin
      phenotype, decreased dermal angiogenesis, and a return to control mouse levels
      for interleukin (IL)-1alpha, IL-6, IL-23 and tumour necrosis factor (TNF)-alpha
      expression and modest reductions in interferon-gamma and IL-17. CONCLUSIONS:
      These findings suggest a critical role for APCs and myeloid cell-derived IL-23
      and TNF-alpha and underscore the importance of Th1 and Th17 T cells in
      maintaining the psoriasiform skin phenotype in the KC-Tie2 mouse model.

PMID- 21070203
TI  - Vitamin D: a novel therapeutic approach for keloid, an in vitro analysis.
AB  - BACKGROUND: Vitamin D and its metabolites play an important role in calcium
      homeostasis, bone remodelling, hormone secretion, cell proliferation and
      differentiation. Recent studies also suggest a beneficial role of vitamin D in
      slowing the progression of tissue fibrosis. However, their effects on dermal
      fibrosis and keloids are unknown. Objectives  To investigate the effect of 1,25
      dihydroxyvitamin D3 (1,25D) in the pathogenesis of tissue fibrosis by keloid
      fibroblasts (KFs). METHODS: KFs were cultured and exposed to different
      concentrations of 1,25D in the presence or absence of transforming growth factor
      (TGF)-beta1. KF phenotypes and protein production were analysed by real-time
      reverse transcriptase-polymerase chain reaction, Western blot, immunofluorescence
      and multiplex enzyme-linked immunosorbent assay techniques. Collagen synthesis
      was evaluated by measuring (3) H-proline incorporation. The effect of 1,25D on
      cell proliferation and viability was evaluated by Formazan assay, proliferating
      cell nuclear antigen expression and the colorimetric conversion of 3-[4, 5
      dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide. RESULTS: We confirmed the
      presence of vitamin D receptors (VDRs) in cultured keloid fibroblasts.
      Fibroblasts transfected with a vitamin D response element reporter construct and
      exposed to the active vitamin D metabolite 1,25D showed increased promoter
      activity indicating VDR functionality in these cells. Incubation of KFs with
      1,25D suppressed TGF-beta1-induced collagen type I, fibronectin and alpha-smooth
      muscle actin expression. 1,25D also modulated plasminogen activator inhibitor-1
      and matrix metalloproteinase-9 expression induced by TGF-beta1. Interestingly,
      1,25D induced hepatocyte growth factor mRNA expression and protein secretion in
      keloid fibroblasts. CONCLUSIONS: This study highlights key mechanistic pathways
      through which vitamin D decreases fibrosis, and provides a rationale for studies
      to test vitamin D supplementation as a preventive and/or early treatment strategy
      for keloid and related fibrotic disorders.

PMID- 21070204
TI  - Avoiding palmar ambiguity in the PREPI: a handprint is approximately 1% body
      surface area.

PMID- 21070206
TI  - Forward genetic dissection of innate response to infection in inbred mouse
      strains: selected success stories.
AB  - Mouse genetics is a powerful tool for the dissection of genes, proteins, and
      pathways important in biological processes. Application of this approach to study
      the host response to infection has been a rich source of discoveries that have
      increased our understanding of the early innate pathways involved in responding
      to microbial infections. Here we review some of the key discoveries that have
      arisen from pinpointing the genetic defect in mouse strains with unusual or
      extreme response to infection and have led to insights into pathogen sensing
      pathways and downstream effector functions of the early innate immune response.

PMID- 21070207
TI  - Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid
      stimulating immunoglobulins.
AB  - Thyroid-stimulating immunoglobulins (TSI) are a functional biomarker of Graves'
      disease (GD). To develop a novel TSI bioassay, a cell line (MC4-CHO-Luc) was bio
      engineered to constitutively express a chimeric TSH receptor (TSHR) and
      constructed with a cyclic adenosine monophosphate (cAMP)-dependent luciferase
      reporter gene that enables TSI quantification. Data presented as percentage of
      specimen-to-reference ratio (SRR%) were obtained from 271 patients with various
      autoimmune and thyroid diseases and 180 controls. Sensitivity of 96% and
      specificity of 99% for untreated GD were attained by receiver operating
      characteristic analysis, area under the curve 0.989, 95% confidence interval
      0.969-0.999, P = 0.0001. Precision testing of manufactured reagents of high,
      medium, low and negative SRR% gave a percentage of coefficient-of-variation of
      11.5%, 12.8%, 14.5% and 15.7%, respectively. There was no observed interference
      by haemoglobin, lipids and bilirubin and no non-specific stimulation by various
      hormones at and above physiological concentrations. TSI levels from GD patients
      without (SRR% 406 +/- 134, mean +/- standard deviation) or under anti-thyroid
      treatment (173 +/- 147) were higher (P < 0.0001) compared with TSI levels of
      patients with Hashimoto's thyroiditis (51 +/- 37), autoimmune diseases without GD
      (24 +/- 10), thyroid nodules (30 +/- 26) and controls (35 +/- 18). The bioassay
      showed greater sensitivity when compared with anti-TSHR binding assays. In
      conclusion, the TSI-Mc4 bioassay measures the functional biomarker accurately in
      GD with a standardized protocol and could improve substantially the diagnosis of
      autoimmune diseases involving TSHR autoantibodies.

PMID- 21070209
TI  - Efficacy and safety of a new immunoglobulin G product, Gammaplex((r)), in primary
      immunodeficiency diseases.
AB  - This open-label multi-centre study evaluated a new intravenous immunoglobulin,
      Gammaplex(r), in the treatment of 50 patients with primary immunodeficiency and
      significant hypogammglobulinaemia. Patients treated previously with other
      intravenous immunoglobulins received Gammaplex(r) on their same infusion schedule
      for 1 year; 22 were on a 21-day and 28 on a 28-day regimen (300-800
      mg/kg/infusion). There were no serious, acute bacterial infections, whereas six
      subjects (12.0%) had at least one such infection in the 6 months before
      enrollment. Forty subjects (80.0%) had at least one non-serious infection; the
      median number of infective episodes per subject per year was 3.07. Antibiotics
      were taken by 38 subjects therapeutically and prophylactically by 16 at some
      time. Fewer than half (46.0%) missed any time off work or school because of
      infection or other illness. Trough immunoglobulin (Ig)G levels were above 6.00
      g/l in all subjects at all assessments after 15 weeks with two exceptions.
      Overall, 21.2% of infusions were associated with an adverse event up to 72 h
      after infusion. The frequency of adverse events increased with infusion rate.
      Headache was the most common product-related adverse event (7.5% of 703
      infusions). In conclusion, Gammaplex(r) is effective in primary immunodeficiency
      and is well tolerated.

PMID- 21070208
TI  - Curcumin induces maturation-arrested dendritic cells that expand regulatory T
      cells in vitro and in vivo.
AB  - Dendritic cells (DC) and regulatory T cells (T(regs) ) are vital to the
      development of transplant tolerance. Curcumin is a novel biological agent
      extracted from Curcuma longa (turmeric), with anti-inflammatory and anti-oxidant
      activity mediated via nuclear factor (NF)-kappaB inhibition. We investigated the
      immunomodulatory effects of curcumin on human monocyte-derived and murine DC.
      Human monocyte-derived DC (hu-Mo-DC) were generated in the presence (CurcDC) or
      absence (matDC) of 25 uM curcumin, and matured using lipopolysaccharide (1
      ug/ml). DC phenotype and allostimulatory capacity was assessed. CD11c(+) DC were
      isolated from C57BL/6 mice, pretreated with curcumin and injected into BALB/c
      mice, followed by evaluation of in vivo T cell populations and alloproliferative
      response. Curcumin induced DC differentiation towards maturation-arrest. CurcDC
      demonstrated minimal CD83 expression (<2%), down-regulation of CD80 and CD86 (50%
      and 30%, respectively) and reduction (10%) in both major histocompatibility
      complex (MHC) class II and CD40 expression compared to matDC. CurcDC also
      displayed decreased RelB and interleukin (IL)-12 mRNA and protein expression.
      Functionally, CurcDC allostimulatory capacity was decreased by up to 60% (P <
      0.001) and intracellular interferon (IFN-gamma) expression in the responding T
      cell population were reduced by 50% (P < 0.05). T cell hyporesponsiveness was due
      to generation of CD4(+) CD25(hi) CD127(lo) forkhead box P3 (FoxP3)(+) T(regs)
      that exerted suppressive functions on naive syngeneic T cells, although the
      effect was not antigen-specific. In mice, in vivo infusion of allogeneic CurcDC
      promoted development of FoxP3(+) T(regs) and reduced subsequent alloproliferative
      capacity. Curcumin arrests maturation of DC and induces a tolerogenic phenotype
      that subsequently promotes functional FoxP3(+) T(regs) in vitro and in vivo.

PMID- 21070211
TI  - Krabbe leukodystrophy in a selected population with high rate of late onset
      forms: longer survival linked to c.121G>A (p.Gly41Ser) mutation.
AB  - Krabbe leukodystrophy (KD) is a neurodegenerative lysosomal disorder caused by
      mutations in the galactocerebrosidase (GALC) gene. Different clinical forms are
      described based on the age at onset. In reported series, the early infantile form
      (EIKD) accounts for more than 90% of the cases. The rarer late onset forms (LOKD)
      become manifest later than 6 months up to the adult age. We report clinical,
      imaging, mutational analysis and geographic data in a large cohort of individuals
      with Krabbe disease examined over a 30-year period. Retrospective analyses of
      disease onset and long-term follow-up were conducted in 26 KD patients. Molecular
      analysis was performed in 12 patients and their families. Nine cases had EIKD,
      and 17 LOKD, accounting for two thirds of our series. No correlation was found
      between enzymatic activity, onset age and disease progression. Despite common
      geographical origin, only in a few cases could parental consanguinity be proven.
      The p.Gly41Ser mutation was associated with longer survival. A wide spectrum of
      LOKD is found despite similar genotype. Although current knowledge about onset
      age, residual enzyme activity and molecular analysis still fail to allow the
      identification of patient candidates for treatment, this information is valuable
      for long-term outcome prediction and could lead to reconsideration of inclusion
      criteria for bone marrow transplant (BMT) or other future therapeutic approaches.

PMID- 21070212
TI  - Duchenne/Becker muscular dystrophy in the family: have potential carriers been
      tested at a molecular level?
AB  - Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular
      disease. After identification of the mutation in the index patient, family
      members can be reliably investigated. Carriers should be informed about their
      risk of having offspring with the disease and about their own risk for
      cardiomyopathy for which regular cardiac surveillance is recommended. In a small
      country like the Netherlands with well-organized genetic services, one would
      expect that most DMD families are adequately informed about the above mentioned
      risks for carriers. We have investigated whether women at risk had been tested at
      a molecular level. In the national Duchenne/Becker database 311 DMD and 99 Becker
      muscular dystrophy (BMD) patients had been registered up to 1 July 2009. These
      patients were asked to give information about the number of sisters and maternal
      aunts of the DMD/BMD patient and anything that was known about their genetic
      status and that of the mother. This information was compared with the information
      known at the genetic laboratory. Thirty-five of 104 adult sisters/maternal aunts
      of DMD patients with a 50% risk of being a carrier and 45 of 148 adult women with
      a 4.3% risk because of germ line mosaicism for DMD had not been tested by DNA
      analysis. Our study indicates that about one third of the potential carriers have
      not been tested. Given the possible far-reaching clinical consequences of being a
      carrier, further studies are needed to investigate the reasons why potential
      female carriers have not been tested.

PMID- 21070210
TI  - Systemic inflammatory responses in progressing periodontitis during pregnancy in
      a baboon model.
AB  - This study tested the hypothesis that pregnant female baboons exhibit increased
      levels of various inflammatory mediators in serum resulting from ligature-induced
      periodontitis, and that these profiles would relate to periodontal disease
      severity/extent in the animals. The animals were sampled at baseline (B), mid
      pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants
      ligated). All baboons developed increased plaque, gingival inflammation and
      bleeding, pocket depths and attachment loss following placement of the ligatures.
      By MP, both prostaglandin E(2) (PGE(2)) and bactericidal permeability inducing
      factor (BPI) were greater than baseline, while increased levels of interleukin
      (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1
      and LBP all decreased from baseline through the ligation phase of the study.
      Stratification of the animals by baseline clinical presentation demonstrated that
      PGE(2), LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval,
      irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly
      lower in the subset of animals that demonstrated the least clinical response to
      ligation, indicative of progressing periodontal disease. PGE(2), macrophage
      chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed
      and secreted (RANTES) and LBP were decreased in the most diseased subset of
      animals at delivery. Systemic antibody responses to Fusobacterium nucleatum,
      Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter
      rectus were associated most frequently with variations in inflammatory mediator
      levels. These results provide a profile of systemic inflammatory mediators during
      ligature-induced periodontitis in pregnant baboons. The relationship of the oral
      clinical parameters to systemic inflammatory responses is consistent with a
      contribution to adverse pregnancy outcomes in a subset of the animals.

PMID- 21070213
TI  - Insight into the genetic cause underlying Kabuki syndrome.

PMID- 21070214
TI  - Large structural polymorphisms predispose genomic sequences to disease-causing
      rearrangements.

PMID- 21070215
TI  - Prevalence of visual field loss following exposure to vigabatrin therapy: a
      systematic review.
AB  - PURPOSE: Vigabatrin is an efficacious antiepileptic drug licensed as add-on
      therapy in refractory epilepsy and used in infantile spasms. Eight years after
      licensing, there emerged a strong and possibly causative association with
      bilateral visual field loss. We report a systematic review ascertaining the
      magnitude of risk of vigabatrin associated visual field loss (VAVFL) and any
      clinical predictors of risk. METHODS: Electronic searches, including MEDLINE
      (1966-2009), EMBASE (1974-2009), and CINAHL (1982-2009), were conducted. Reports,
      published in full, of observational studies investigating the prevalence of
      visual field loss in patients with partial epilepsy treated with vigabatrin were
      included. Outcomes were the proportion with visual field loss, and the relative
      risk of VAVFL compared to similar nonexposed patients with epilepsy. KEY
      FINDINGS: Thirty-two studies were identified, which included 1,678 patients
      exposed to vigabatrin and 406 controls. Of the 1,678 exposed patients, 738 (44%)
      had visual field loss compared to just 30 (7%) among the 406 controls. The random
      effects estimate for the proportion of adults with visual field loss was 52% [95%
      confidence interval (CI) 46-59]. The estimate for children was lower at 34% (95%
      CI 25-42). The relative risk for field loss in vigabatrin-exposed patients was
      4.0 (95% CI 2.9-5.5). Larger mean cumulative dose of vigabatrin and increasing
      age were associated with a higher proportion of patients with visual field loss.
      SIGNIFICANCE: Vigabatrin should be reserved for patients with epilepsy for whom
      there is no other alternative or for patients who have determined the benefit of
      ongoing treatment to outweigh the risk of VAVFL.

PMID- 21070216
TI  - Factors predictive of resilience and vulnerability in new-onset epilepsy.
AB  - PURPOSE: Epilepsy has been associated with reduced quality of life (QOL), but QOL
      outcomes are heterogeneous. Some people are able to maintain a good QOL despite
      poorly controlled epilepsy and others report poor QOL despite well-controlled
      epilepsy. Maintaining a good QOL in the face of adversity is embodied by the
      concept of resilience. We explored the factors associated with having a resilient
      outcome in people with epilepsy (PWE). Our definition of adversity included
      socioeconomic disadvantage as well as continuing seizures. METHODS: We analyzed
      data collected as part of the Standard and New Antiepileptic Drugs (SANAD) trial.
      At the end of 4-year follow-up, patients were classified into four groups on the
      basis of seizure control (good/poor) and socioeconomic status
      (advantaged/disadvantaged). We identified individuals with resilient and
      vulnerable outcomes and the factors associated with having them. KEY FINDINGS:
      Seizure control was more important in determining QOL than material advantage,
      but socioeconomic status appeared to act as an additional protective or risk
      factor for QOL. Significant predictors of a resilient outcome were absence of
      depression and fewer adverse treatment effects at 4 years and good QOL at
      baseline. Significant predictors of a vulnerable outcome were fair/poor health
      perception, presence of depression, reduced sense of mastery, and more adverse
      treatment effects at follow-up. SIGNIFICANCE: Reducing the adverse effects of
      treatment, along with psychosocial interventions to increase self-mastery, reduce
      health concerns, treat depression, and promote positive adjustment to a diagnosis
      will likely improve the QOL of PWE despite less favorable clinical and
      socioeconomic circumstances.

PMID- 21070217
TI  - Topographic movie of intracranial ictal high-frequency oscillations with seizure
      semiology: epileptic network in Jacksonian seizures.
AB  - PURPOSE: We developed a technique to produce images of dynamic changes in ictal
      high-frequency oscillations (HFOs) >40 Hz recorded on subdural
      electroencephalography (EEG) that are time-locked to the ictal EEG and ictal
      semiology video. We applied this technique to Jacksonian seizures to demonstrate
      ictal HFO propagation along the homunculus in the primary sensory-motor cortex to
      visualize the underlying epileptic network. METHODS: We analyzed intracranial
      ictal EEGs from two patients with intractable Jacksonian seizures who underwent
      epilepsy surgery. We calculated the degrees of increase in amplitude within 40
      80, 80-200, and 200-300 Hz frequency bands compared to the interictal period and
      converted them into topographic movies projected onto the brain surface picture.
      We combined these data with the ictal EEGs and video of the patient demonstrating
      ictal semiology. KEY FINDINGS: The ictal HFOs began in the sensory cortex and
      appeared concomitantly with the sensory aura. They then propagated to the motor
      cortex at the same time that focal motor symptoms evolved. As the seizure
      progressed, the ictal HFOs spread or reverberated in the rolandic region.
      However, even when the seizure became secondarily generalized, the ictal HFOs
      were confined to the rolandic region. In both cases, there was increased
      amplitude of higher frequency bands during seizure initiation compared to seizure
      progression. SIGNIFICANCE: This combined movie showed the ictal HFO propagation
      corresponding to the ictal semiology in Jacksonian seizures and revealed the
      epileptic network involved in seizure initiation and progression. This method may
      advance understanding of neural network activities relating to clinical seizure
      generation and propagation.

PMID- 21070218
TI  - Altered physiology and pharmacology in the corticostriatal system in a model of
      temporal lobe epilepsy.
AB  - PURPOSE: Temporal lobe epilepsy (TLE) is associated with changes in hippocampal
      function/morphology. These changes often manifest as a decline in cognitive
      abilities, which in animal models is reflected in reduced spatial learning and up
      regulation or down-regulation of synaptic plasticity. Beyond this, however,
      changes also occur in other, extralimbic structures, as has been shown on the
      neurochemical level. Here, our aim was to test whether functional changes occur
      also in corticostriatal synaptic communication, also because the striatum is
      instrumental in motor planning and coordination and hence serves important
      nonlimbic functions. METHODS: We analyzed corticostriatal long-term potentiation
      (LTP) in brain slices of pilocarpine-treated rats after status epilepticus (SE).
      To determine whether chronic seizures, or SE itself, impact basal ganglia
      function, tissue was investigated (1) shortly after SE (3-5 days, acute group),
      and (2) after chronic epilepsy had been established (chronic group, 4-10 weeks
      after SE). KEY FINDINGS: Early after SE, only little synaptic plasticity emerged.
      In the chronic group, however, LTP was enhanced significantly in the SE group
      versus control preparations. Using pharmacologic blockade of N-methyl-d-aspartate
      (NMDA) receptors, LTP in chronically epileptic tissue could be dissected into an
      early, NMDA-dependent and a late, NMDA-independent phase, which reverted to LTD
      with additional dopamine D1/D5 receptor blockade. SIGNIFICANCE: We conclude that
      chronic limbic epilepsy goes along also with functional alterations in
      extralimbic structures such as the striatum.

PMID- 21070219
TI  - Modelling the resource implications of managing adults with Fabry disease in
      Norway favours home infusion.
AB  - BACKGROUND: The aim of this study was to estimate the resource implications and
      budget impact of managing adults with Fabry disease in Norway, from the
      perspective of the publicly funded healthcare system. METHODS: A decision model
      was constructed using published clinical outcomes and clinician-derived resource
      utilization estimates. The model was used to estimate the annual healthcare cost
      of managing a cohort of 64 adult Fabry patients in an average year. RESULTS: The
      expected annual cost of managing 60 existing Fabry patients and four new patients
      in Norway each year was estimated to be NOK 55.8 million (?6.7 million). In an
      average year, patients receiving enzyme replacement therapy (ERT) with agalsidase
      alfa (Replagal((r))) at 0.2 mg kg-1 or agalsidase beta (Fabrazyme((r))) at 1.0 mg
      kg-1 are collectively expected to make 586 attendances to their family
      practitioner's office for their infusions, which equates to 128 eight-hour days
      associated with ERT. Encouraging more patients to undergo home-based infusions
      has substantial potential to free-up community-based resources. In comparison,
      the community-related benefit that can be obtained by switching from agalsidase
      beta (1.0 mg kg-1) to agalsidase alpha (0.2 mg kg-1) is marginal, and dependent
      on the two doses being clinically equivalent. CONCLUSION: Maximizing the
      proportion of adults with Fabry disease undergoing home-based infusions has the
      potential to release community-based resources for alternative use by non-Fabry
      patients, thereby improving the efficiency of the publicly funded healthcare
      system in Norway.

PMID- 21070221
TI  - Autophagy as a mechanism for myolysis of cardiomyocytes in mitral regurgitation.
AB  - BACKGROUND: Myolysis of atrial cardiomyocytes occurs in patients with severe
      mitral and tricuspid regurgitation. This morphological remodelling may involve
      autophagy. METHODS: This study comprised 20 patients (10 with long-standing
      persistent atrial fibrillation and 10 with sinus rhythm) with severe mitral and
      tricuspid regurgitation. Atrial appendageal tissues were obtained during surgery.
      The appearance of autophagosomes (LC3B) in myocytes can reflect autophagy
      induction. Complement 9 is used as a reliable marker of oncosis. RESULTS: In the
      fibrillating right atria, 68.4 +/- 18.9% of total myocytes showed moderate-to
      severe myolysis, while 64.2 +/- 15.8% of total myocytes comprised these cells in
      right atrial myocardium with sinus rhythm. Immunohistochemical study revealed
      LC3B-positive myocytes in 8.0% of myocytes without myolysis, 11.9% of myocytes
      with mild myolysis and 49.4% of myocytes with moderate-to-severe myolysis in
      right atrial myocardium with sinus rhythm (P < 0.0001). Similarly, in the
      fibrillating right atria, LC3B-positive myocytes were observed in 5.9% of
      myocytes without myolysis, 12.2% of myocytes with mild myolysis and 50.7% of
      myocytes with moderate-to-severe myolysis (P < 0.0001). Moreover, in the
      fibrillating left atria, LC3B-positive myocytes were observed in 4.9% of myocytes
      without myolysis, 12.6% of myocytes with mild myolysis and 52.0% of myocytes with
      moderate-to-severe myolysis (P < 0.0001). None of the atrial myocytes displayed
      intracellular deposition of complement 9. CONCLUSIONS: Induction of autophagy,
      but not oncosis, occurs in most cases of atrial cardiomyocytes with severe mitral
      and tricuspid regurgitation, even those without atrial fibrillation, and is
      closely associated with the development of myolysis in this disease.

PMID- 21070220
TI  - Impaired anti-inflammatory efficacy of n-butyrate in patients with IBD.
AB  - BACKGROUND: The intestinal mucosa of patients with inflammatory bowel diseases
      (IBD) characteristically shows a high degree of inflammation when compared to
      healthy subjects. This appears to be attributable to an imbalance in local
      reactivity of inflammatory cells. In the present study, we tested the hypothesis
      that immune cells from patients with IBD are less sensitive to anti-inflammatory
      agents in the gut as exemplified by the short-chain fatty acid (SCFA) n-butyrate.
      MATERIAL AND METHODS: Peripheral blood mononuclear cells (PBMC) of patients with
      IBD (22 Crohn's Disease, CD; 9 Ulcerative Colitis, UC) and 20 healthy individuals
      were stimulated through TLR-4 and TLR-2 engagement, respectively, and the anti
      inflammatory activity of n-butyrate (0.06-1 mM) on cytokine production (IL-1beta,
      IL-10, IL-12/23p40, TNF-alpha) was assessed. Inhibition curves were generated,
      and effective doses (ED20-ED80) were determined. RESULTS: Hyperresponsiveness to
      TLR-2 activation reflected by increased IL-12/23p40 and TNF-alpha production was
      observed in patients with IBD. To inhibit the release of IL-12/23p40 from PBMC
      after activation via TLR2-agonists, higher concentrations of n-butyrate were
      required in patients with IBD , when compared to healthy subjects. With regard to
      TLR-4 activation, PBMC from patients with IBD and controls were equally
      responsive to the immunoregulatory effects of n-butyrate. Further analysis
      revealed that the impaired sensitivity of PBMC to the anti-inflammatory action of
      n-butyrate was independent from hyperreactivity of immunocompetent cells.
      CONCLUSIONS: Impaired sensitivity to the inhibitory action of n-butyrate in IBD
      may constitute a determinant in the pathogenesis of these inflammatory diseases.

PMID- 21070222
TI  - Cost analysis and cost-effectiveness of NT-proBNP-guided heart failure specialist
      care in addition to home-based nurse care.
AB  - BACKGROUND: Heart failure management programmes have been shown to reduce re
      hospitalizations. We recently investigated a new disease management programme
      comparing usual care (UC) to home-based nurse care (HNC) and a HNC group in which
      decision-making was based on NT-proBNP levels (BNC). As re-hospitalization is the
      main contributing economic factor in heart failure expenditures, we hypothesized
      that this programme might be able to reduce costs and could be conducted cost
      effectively compared to UC. METHODS: One hundred and ninety congestive heart
      failure patients, who were included in a randomized trial to receive UC, HNC or
      BNC at discharge, were analysed in a cost-effectiveness model. Different models
      were applied to perform analysis of all medical costs, and the costs per year
      survived were chosen as an effectiveness parameter. RESULTS: Per patient costs
      because of heart failure treatment in the UC and the BNC group were ? 7109 +/-
      11,687 and ? 2991 +/- 4885 (P=0.027), respectively. Corrected for death as a
      competing risk, the costs in the UC group were ? 7893 +/- 11,734 and were reduced
      by BNC to ?3148 +/- 4949 (P=0.012). Considering costs because of all-cause re
      hospitalizations, calculated costs per year survived after discharge were ?
      19,694 +/- 26,754 for UC, ? 14,262 +/- 25 330 for HNC (P > 0.05) and ? 8784 +/-
      14,728 for BNC (t-test-based contrast P=0.015). In all models calculated, HNC was
      cost neutral. CONCLUSIONS: NT-BNP-guided heart failure specialist care in
      addition to home-based nurse care is cost effective and cheaper than standard
      care, whereas HNC is cost neutral.

PMID- 21070223
TI  - The advent of mandatory data archiving.

PMID- 21070224
TI  - Contact allergy to aliphatic polyisocyanates based on hexamethylene-1,6
      diisocyanate (HDI).
AB  - BACKGROUND: Aliphatic polyisocyanates based on hexamethylene 1,6-diisocyanate
      (HDI) are components of lacquers, coatings, and spray paints. They are mainly
      composed of HDI trimers, but also contain larger oligomers, and minute amounts of
      HDI monomers (<1%). HDI trimers occur as biuret, isocyanurate and asymmetrical
      types. OBJECTIVES: We report on 4 patients with allergic contact
      dermatitis/contact allergy resulting from HDI-based polyisocyanates in
      polyurethane paints. METHODS: The patients were examined at the Finnish Institute
      of Occupational Health in 2000-2009. The first two patients were diagnosed by
      testing with their own polyurethane hardeners and ingredients of the hardeners.
      In 2002, HDI isocyanurate (HDI-IC) trimer was added to our isocyanate series, and
      the last two patients were screened with the series. RESULTS: Patient no. 1 was
      exposed and sensitized to HDI biuret trimer, patient no. 2 to HDI-IC trimer, and
      patient no. 4 to HDI asymmetrical trimer. Patient no. 3 was positive with HDI-IC
      trimer. He had been handling several paint hardeners containing HDI-based
      polyisocyanates, but the subtypes of the trimers remained unidentified. All 4
      patients were negative with HDI monomer. CONCLUSIONS: HDI trimers are novel
      contact allergens in workers who handle polyurethane paints. The allergic
      reactions cannot be explained by sensitization to HDI monomer.

PMID- 21070225
TI  - Photoallergic contact dermatitis caused by occupational exposure to the canine
      non-steroidal anti-inflammatory drug carprofen.

PMID- 21070226
TI  - Occupational allergic contact dermatitis caused by basil (Ocimum basilicum).

PMID- 21070227
TI  - Prevalence and burden of headache disorders: a comparative regional study in
      China.
AB  - Background.- Since the early 1990s, no study has been undertaken examining the
      prevalence and burden of headache disorders in China. Objective.- We conducted a
      one-year survey on the prevalence and burden of primary headache in the Chinese
      provinces of Guangdong and Guangxi. Our study also evaluated the factors behind
      similarities and differences affecting prevalence in the 2 regions of study.
      Methods.- Random samples of 372 local residents in Guangdong and 182 local
      residents in Guangxi aged 18-65 years were invited to a face-to-face interview.
      Results.- The one-year prevalence of primary headache was 22.6% (84/372) in
      Guangdong and 41.2% (75/182) in Guangxi. The prevalence of migraine (14.3%, n =
      26) in Guangxi was higher than prevalence of migraine (8.3%, n = 31) in Guangdong
      (P = .03). The ratio of headache cost and household income was 2.1% in Guangdong
      and 3.7% in Guangxi, the ratio in Guangdong was less than that in Guangxi (P =
      .001). The diagnostic confirmation rate of migraine was low. No migraineur used
      triptans drugs to treat migraine in either region. Conclusion.- Migraine
      prevalence was higher in the lower-income region that also contains a higher
      proportion of ethnic minorities. Although there was no difference of headache
      cost between the 2 regions, the headache populations in the lower-income region
      would relatively suffer a greater financial burden if taking the economic
      differences between the 2 regions into account. The improvement of diagnostic and
      therapeutic levels for the treatment of headache, especially migraine, in the 2
      regions may be a matter of urgency.

PMID- 21070228
TI  - A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate
      for the prophylactic treatment of chronic migraine.
AB  - OBJECTIVE: This multi-center pilot study compared the efficacy of
      onabotulinumtoxinA with topiramate (a Food and Drug Administration approved and
      widely accepted treatment for prevention of migraine) in individuals with chronic
      migraine (CM). METHODS: A total of 59 subjects with CM were randomly assigned to
      one of 2 groups: Group 1 (n = 30) received topiramate plus placebo injections,
      Group 2 (n = 29) received onabotulinumtoxinA injections plus placebo tablets.
      Subjects maintained daily headache diaries over a 4-week baseline period and a 12
      week active study period. The primary endpoint was the Physician Global
      Assessment, which measured the treatment responder rate and indicated improvement
      in both groups over 12 weeks. Secondary endpoints, measured at weeks 4 and 12,
      included headache days per month, migraine days, headache-free days, days on
      acute medication, severity of headache episodes, Migraine Impact & Disability
      Assessment, Headache Impact Test, effectiveness of and satisfaction with current
      treatment on the amount of medication needed, and the frequency and severity of
      migraine symptoms. At 12 weeks subjects were re-evaluated and tapered off oral
      study medications over a 2-week time period. Subjects not reporting a >50%
      reduction of headache frequency at 12 weeks were invited to participate in a 12
      week open label extension study with onabotulinumtoxinA. Of these, 20 subjects, 9
      from the Topiramate Group and 11 from the OnabotulinumtoxinA Group, volunteered
      for this extension from weeks 14 to 26. RESULTS: This study demonstrated positive
      benefit for both onabotulinumtoxinA and topiramate in subjects with CM. Overall,
      the results were statistically significant within groups but not between groups.
      By week 26, subjects had a reduction of headache days per month compared with
      baseline. This was a significant within-group finding. CONCLUSION:
      OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with
      CM as determined by Global Physician Assessment and supported by multiple
      secondary endpoint measures.

PMID- 21070229
TI  - Excellent tolerability but relatively low initial clinical efficacy of
      telcagepant in migraine.
AB  - In 3 randomized clinical trials (n = 1585) the calcitonin gene-related peptide
      antagonist telcagepant 300 mg orally had an incidence of adverse events similar
      to placebo when used in the acute treatment of migraine. Telcagepant, thus, has
      excellent tolerability in migraine. Only a quarter (26%) (334/1307) of patients
      were, however, pain free after 2 hours, while 56% (729/1297) of patients had pain
      relief at 2 hours. Telcagepant 300 mg in one randomized clinical trial was
      equipotent to zolmitriptan 5 mg. Based on results from a meta-analysis,
      rizatriptan 10 mg (41%) and almotriptan (35%) seem superior to telcagepant (26%)
      for pain free at 2 hours whereas rizatriptan 10 mg (25%) showed no difference
      from telcagepant 300 mg (19 %) for sustained pain free (2-24 hours). The
      introduction of calcitonin gene-related peptide receptor antagonism in the acute
      treatment of migraine is a major step forward but so far mostly because of its
      specific mode of action and excellent tolerability.

PMID- 21070231
TI  - Amitriptyline in the prophylactic treatment of migraine and chronic daily
      headache.
AB  - OBJECTIVE AND BACKGROUND: Amitriptyline is one of the most commonly used
      medications in migraine prophylaxis. There have been relatively few placebo
      controlled studies of amitriptyline in migraine prophylaxis or in treatment of
      chronic daily headache (CDH). This report deals with a large placebo-controlled
      trial of amitriptyline vs placebo of 20 weeks duration that included subjects
      with intermittent migraine (IM) as well as CDH. The study was carried out between
      1976 and 1979; however, results have never been fully reported. METHODS: Patients
      with a history of migraine as defined by the 1962 Ad Hoc Committee report were
      recruited for this study. Subjects had at least 2 headaches per month, and no
      limit was placed on the number of headaches per month that could be experienced.
      The study format included a 4-week baseline period (Period A) in which all
      subjects received placebo in a dose of 2 pills per day for one week, 3 pills per
      day for one week and then 4 pills per day for 2 weeks. Subjects with at least 2
      migraine headaches in this period were then entered into Period B and randomized
      into either amitriptyline or placebo tracks. Medication consisted of identical
      tablets containing either 25 mg amitriptyline or placebo. Period B was 4 weeks in
      duration with dose titration identical to Period A. The dose could be reduced if
      necessary to reduce side effects. The minimum dose was one pill per day. Period C
      was a 12-week maintenance or stabilization period in which the patient continued
      the dose established by week 8 with visits at weeks 12, 16, and 20. Patients kept
      a headache calendar that was used for data collection. Headache frequency (per
      month), severity, and duration (hours) were the primary measurement parameters
      employed for data analysis. RESULTS: For the entire group, 391 subjects were
      entered into Period A, 338 were randomized into Period B, 317 (81%) subjects
      completed the first post-randomization visit (8 weeks), 255 (65%) completed week
      12, 210 (54%) completed week 16, and 186 (48%) completed week 20. Using headache
      frequency and evaluating parameters of (a) improvement, (b) no change, or (c)
      worsening relative to baseline, there was a significant improvement in headache
      frequency for amitriptyline over placebo at 8 weeks (P = .018) but not at 12, 16,
      or 20 weeks. When amitriptyline and placebo patients were compared for headache
      frequency at 8, 12, 16, and 20 weeks to their own placebo stabilization period at
      4 weeks, statistically significant improvement vs worsening was seen in headache
      frequency at each evaluation point for both amitriptyline and placebo groups (P
      <= .01) reaching 50% reporting a decrease in frequency in each group and
      approximately 10% reporting worsening by week 20. There were no significant
      differences in headache severity or duration between amitriptyline and placebo
      groups at anytime during the study. Within the study sample, there were 36
      amitriptyline and 22 placebo subjects who had headaches >= 17 days/month that fit
      the current definition of CDH by the Silberstein-Lipton criteria. These were
      analyzed separately as a subgroup for comparison of amitriptyline vs placebo
      using a metric of (1) no change or worsening; (2) up to a 50% improvement; and
      (3) >= 50% improvement in headache frequency. Amitriptyline was superior to
      placebo in number with improvement in frequency of >= 50% at 8 weeks (25% vs 5%
      [P = .031]) and at 16 weeks (46% vs 9% [P = .043]). There was a trend for
      amitriptyline to be superior to placebo at 12 and 20 weeks but this did not reach
      significance. CONCLUSIONS: In this study, using headache frequency as the primary
      metric, for the entire group, amitriptyline was superior to placebo in migraine
      prophylaxis at 8 weeks but, because of a robust placebo response, not at
      subsequent time points. For the subgroup with CDH, amitriptyline was
      statistically significantly superior to placebo at 8 weeks and 16 weeks with a
      similar but nonsignificant trend at 12 and 20 weeks. Compared with placebo
      amitriptyline is effective in CDH. Amitriptyline was also significantly effective
      in IM compared intragroup to its own baseline; however, placebo was equally
      effective in the same analysis. The reason for the robust placebo response in the
      IM group is not clear, but has been occasionally reported.

PMID- 21070230
TI  - Long-term tolerability of telcagepant for acute treatment of migraine in a
      randomized trial.
AB  - OBJECTIVE: To evaluate the long-term tolerability of telcagepant for acute
      treatment of intermittent migraine attacks. Background.- Telcagepant is a
      calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for
      the acute treatment of migraine. METHODS: Migraine patients were randomized 2:1
      to double-blind treatment with telcagepant 280/300 mg or rizatriptan 10 mg for an
      acute mild, moderate, or severe migraine. Patients could administer a second dose
      within 2-24 hours for nonresponse or migraine recurrence. Patients could treat up
      to 8 attacks per month for up to 18 months. Safety assessments included
      spontaneous reports of adverse events and collection of vital signs,
      electrocardiograms, and laboratory assessments. The primary endpoint was the
      percentage of patients with >= 1 triptan-related adverse events in the 14-day
      period post dose. RESULTS: Of 1068 patients randomized, 641 (90%) patients
      treated >= 1 attack with telcagepant and 313 (88%) treated >= 1 attack with
      rizatriptan. A total of 19,820 attacks were treated with telcagepant (mean per
      patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Fewer triptan
      related adverse events (difference: -6.2%; 95% CI -10.4, -2.6; P < .001) and drug
      related adverse events (difference: -15.6%; 95% CI -22.2, -9.0) were reported for
      telcagepant vs rizatriptan. The most common adverse events appeared to have
      generally similar incidence proportions between the treatment groups. Those with
      an incidence > 5% in the telcagepant group were dry mouth (9.7%, rizatriptan =
      13.7%), somnolence (9.2%, rizatriptan = 16.6%), dizziness (8.9%, rizatriptan =
      10.2%), and nausea (9.0%, rizatriptan = 6.4%). CONCLUSIONS: Telcagepant was
      generally well tolerated when administered for the acute intermittent treatment
      of migraine for up to 18 months. The incidences of triptan-related and drug
      related adverse events favored telcagepant over rizatriptan.

PMID- 21070232
TI  - Targets of somatic hypermutation within immunoglobulin light chain genes in
      zebrafish.
AB  - In mammals, somatic hypermutation (SHM) of immunoglobulin (Ig) genes is critical
      for the generation of high-affinity antibodies and effective immune responses.
      Knowledge of sequence-specific biases in the targeting of somatic mutations can
      be useful for studies aimed at understanding antibody repertoires produced in
      response to infections, B-cell neoplasms, or autoimmune disease. To evaluate
      potential nucleotide targets of somatic mutation in zebrafish (Danio rerio), an
      enriched IgL cDNA library was constructed and > 250 randomly selected clones were
      sequenced and analysed. In total, 55 unique VJ-C sequences were identified
      encoding a total of 125 mutations. Mutations were most prevalent in V(L) with a
      bias towards single base transitions and increased mutation in the
      complementarity-determining regions (CDRs). Overall, mutations were
      overrepresented at WRCH/DGYW motifs suggestive of activation-induced cytidine
      deaminase (AID) targeting which is common in mice and humans. In contrast to
      mammalian models, N and P addition was not observed and mutations at AID hotspots
      were largely restricted to palindromic WRCH/DGYW motifs. Mutability indexes for
      di- and trinucleotide combinations confirmed C/G targets within WRCH/DGYW motifs
      to be statistically significant mutational hotspots and showed trinucleotides ATC
      and ATG to be mutation coldspots. Additive mutations in VJ-C sequences revealed
      patterns of clonal expansion consistent with affinity maturation responses seen
      in higher vertebrates. Taken together, the data reveal specific nucleotide
      targets of SHM in zebrafish and suggest that AID and affinity maturation
      contribute to antibody diversification in this emerging immunological model.

PMID- 21070233
TI  - Evolution of CD33-related siglecs: regulating host immune functions and escaping
      pathogen exploitation?
AB  - Sialic-acid-binding immunoglobulin-like lectins, siglecs, are important immune
      receptors expressed widely in mammals. A unique feature of siglecs is their
      ability to bind sialylated glycans and transmit signals to immune cells. The CD33
      related siglecs (CD33rSiglecs) form a major subfamily of the siglecs, containing
      a large, rapidly evolving group of genes that expanded in mammals through an
      inverse duplication event involving a primordial cluster of siglec genes over 180
      million years ago. Humans express a much larger set of CD33rSiglecs than mice and
      rats, a feature that can be explained by a dramatic loss of CD33rSiglec genes in
      rodents. Most CD33rSiglecs have immune receptor tyrosine-based inhibitory motifs
      and signal negatively. Interestingly, novel DAP-12-coupled 'activating'
      CD33rSiglecs have been identified, such as siglec-14 and siglec-16, which are
      paired with the inhibitory receptors, siglec-5 and siglec-11, respectively. The
      evolution of these activating receptors may have been driven in part by pathogen
      exploitation of inhibitory siglecs, thereby providing the host with additional
      pathways by which to combat these pathogens. Inhibitory siglecs seem to play
      important and varied roles in the regulation of host immune responses. For
      example, several CD33rSiglecs have been implicated in the negative regulation of
      Toll-like receptor signalling during innate responses; siglec-G functions as a
      negative regulator of B1-cell expansion and appears to suppress inflammatory
      responses to host-derived 'danger-associated molecular patterns'. Recent work has
      also shown that engagement of neutrophil-expressed siglec-9 by certain strains of
      sialylated Group B streptococci can suppress killing responses, thereby providing
      experimental support for pathogen exploitation of host CD33rSiglecs.

PMID- 21070234
TI  - Engagement of glycosylphosphatidylinositol-anchored proteins results in enhanced
      mouse and human invariant natural killer T cell responses.
AB  - Invariant natural killer T (iNKT) cells are a small subset of lymphocytes that
      recognize glycolipid antigens in the context of CD1d and consequently produce
      large quantities of pro-inflammatory and/or anti-inflammatory cytokines. Several
      transmembrane glycoproteins have been implicated in the co-stimulation of iNKT
      cell responses. However, whether glycosylphosphatidylinositol (GPI)-anchored
      proteins can function in this capacity is not known. Here, we demonstrate that
      antibody-mediated cross-linking of the prototype mouse GPI-anchored protein Thy-1
      (CD90) on the surface of a double-negative (CD4-CD8-) iNKT cell line leads to
      cytokine production at both the mRNA and protein levels. In addition, Thy-1
      triggering enhanced cytokine secretion by iNKT cells that were concomitantly
      stimulated with alpha-galactosylceramide (alphaGC), consistent with a co
      stimulatory role for Thy-1 in iNKT cell activation. This was also evident when a
      CD4+ mouse iNKT cell line or primary hepatic NKT cells were stimulated with
      alphaGC and/or anti-Thy-1 antibody. Cross-linking Ly-6A/E, another GPI-anchored
      protein, could also boost cytokine secretion by alphaGC-stimulated iNKT cells,
      suggesting that the observed effects reflect a general property of GPI-anchored
      proteins. To extend these results from mouse to human cells, we focused on CD55,
      a GPI-anchored protein that, unlike Thy-1, is expressed on human iNKT cells.
      Cross-linking CD55 augmented alphaGC-induced iNKT cell responses as judged by
      more vigorous proliferation and higher CD69 expression. Collectively, these
      findings demonstrate for the first time that GPI-anchored proteins are able to co
      stimulate CD1d-restricted, glycolipid-reactive iNKT cells in both mice and
      humans.

PMID- 21070235
TI  - Cytokine reporter mice in immunological research: perspectives and lessons
      learned.
AB  - Cytokines are soluble messenger molecules with important regulatory functions
      throughout the immune system. 'Cytokine reporter' strains express marker
      molecules under control of elements from cytokine genes allowing for easy
      identification of their cellular sources. Such systems are well-accepted tools
      for research of cytokine function. The value of these strains lies in the ability
      to perform experiments relying on identification and isolation of live cytokine
      expressing cells, provided that the reporter faithfully reflects the proper
      cytokine mRNA and protein production. As more diverse cell subsets are defined by
      their cytokine expression, the field has adapted with the generation of more
      sophisticated strains. In this review we summarize the evolution of cytokine
      detection methods and give examples of knowledge gained using cytokine reporter
      mice for cell types expressing interferon-gamma and interleukin-4, -10 and -17.
      We also discuss current options for generating such reporter strains and their
      potential pitfalls.

PMID- 21070236
TI  - Integrative analysis correlates donor transcripts to recipient autoantibodies in
      primary graft dysfunction after lung transplantation.
AB  - Up to one in four lung-transplanted patients develop pulmonary infiltrates and
      impaired oxygenation within the first days after lung transplantation. Known as
      primary graft dysfunction (PGD), this condition increases mortality
      significantly. Complex interactions between donor lung and recipient immune
      system are the suspected cause. We took an integrative, systems-level approach by
      first exploring whether the recipient's immune response to PGD includes the
      development of long-lasting autoreactivity. We next explored whether proteins
      displaying such differential autoreactivity also display differential gene
      expression in donor lungs that later develop PGD compared with those that did
      not. We evaluated 39 patients from whom autoantibody profiles were already
      available for PGD based on chest radiographs and oxygenation data. An additional
      nine patients were evaluated for PGD based on their medical records and set aside
      for validation. From two recent donor lung gene expression studies, we reanalysed
      and paired gene profiles with autoantibody profiles. Primary graft dysfunction
      can be distinguished by a profile of differentially reactive autoantibodies
      binding to 17 proteins. Functional analysis showed that 12 of these proteins are
      part of a protein-protein interaction network (P=3 x 10-6) involved in
      proliferative processes. A nearest centroid classifier assigned correct PGD
      grades to eight out of the nine patients in the validation cohort (P=0.048). We
      observed significant positive correlation (r=0.63, P=0.011) between differences
      in IgM reactivity and differences in gene expression levels. This connection
      between donor lung gene expression and long-lasting recipient IgM autoantibodies
      towards a specific set of proteins suggests a mechanism for the development of
      autoimmunity in PGD.

PMID- 21070237
TI  - Biomechanics of the macaque postorbital septum investigated using finite element
      analysis: implications for anthropoid evolution.
AB  - Finite element analysis was used to assess whether the postorbital septum plays a
      meaningful biomechanical role as a structural support for the circumorbital
      region in a species of macaque, an anthropoid primate. A finite element model was
      constructed of a Macaca fascicularis cranium that was subsequently modified to
      create a second model in which the septum was removed bilaterally. The models
      were subjected to forces and constraints simulating a molar bite, and resulting
      strains and displacements were recorded. Strain magnitudes at selected locations
      on the models were typically lower or unchanged in the model lacking septae,
      which would seem to be contrary to expectations. However, more broadly, relative
      to the model containing septae, the model without septae exhibited a mosaic
      pattern of strain increases and decreases in the circumorbital region. The model
      lacking septae also exhibited more asymmetric displacements in the orbital
      region, although not in precisely the manner predicted by prior experimental
      studies. Overall, the mechanical impact of the postorbital septum is minimal in
      macaques. These results, when considered along with those of prior experimental
      studies, suggest that either the postorbital septum in anthropoids did not evolve
      for mechanical reasons, or, if it did, it no longer plays such a role in extant
      taxa.

PMID- 21070238
TI  - Climate, history and neutrality as drivers of mammal beta diversity in Europe:
      insights from multiscale deconstruction.
AB  - 1. Environmental sorting, historical factors and neutral dynamics may all drive
      beta diversity (change in species composition across space), but their relative
      importance remains unresolved. In the case of European mammals, key potential
      drivers of large-scale beta diversity include current climate, neutral dynamics
      and two historical factors: Pleistocene glaciations and peninsular dynamics
      (immigration from extra-regional eastern faunal source areas and inter-linked
      relictual survival and evolutionary differentiation in isolated areas). 2. We
      assessed the relative importance of these drivers using a novel analytical
      framework to deconstruct beta diversity of non-volant mammals in Europe (138
      species) into its turnover (change in species composition because of species
      replacements) and nestedness components (change in species composition because of
      species richness differences) at continental and regional (250,000 km(2) )
      scales. 3. We found continental-scale mammal beta diversity to be mainly caused
      by spatial turnover (99.9%), with only a small contribution (0.1%) from
      nestedness. 4. Current climate emerged as an important driver of beta diversity,
      given the strong continental-scale turnover, particularly in north-south
      direction, i.e., in line with the latitudinal climate gradient, and, more
      directly, the strong correlation of climate with spatial turnover at both
      continental and regional scales. 5. However, there was also evidence for the
      importance of non-climatic drivers. Notably, the compositional variation purely
      accounted for by space was greater than that purely accounted for by environment
      for both the turnover and the nestedness component of beta diversity.
      Furthermore, the strong longitudinal turnover within Southern Europe is in
      accordance with the region's long-term climatic stability having allowed multiple
      refugia and local evolutionary diversification. As expected from peninsular
      dynamics, there was increasing dissimilarity with geographic distance in an east
      west direction because of nestedness, but only in Central and Northern Europe. 6.
      In conclusion, European mammal beta diversity mainly reflects spatial turnover
      and only to a limited extent nestedness and is driven by current climate in
      combination with historical - and perhaps, neutral - dynamics. These findings
      suggest that a key challenge for climate-change predictive studies will be taking
      the influence of non-climatic factors into account.

PMID- 21070239
TI  - Developmental validation of feline, bovine, equine, and cervid quantitative PCR
      assays.
AB  - Accurate DNA quantification is essential for optimizing DNA testing and
      minimizing sample consumption. Real-time quantitative polymerase chain reaction
      (qPCR) assays have been published for human and canine nuclear DNA, and the need
      for quantifying other forensically important species was evident. Following the
      strategy employed for the canine qPCR assay, we developed individual assays to
      accurately quantify feline, bovine, equine, and cervid nuclear DNA. Each TaqMan
      based assay incorporates a genus-specific probe targeting the Melanocortin-1
      Receptor gene and includes a piece of synthetic DNA that acts as an internal PCR
      control for detecting inhibition. Developmental validations were carried out
      following the revised guidelines of the Scientific Working Group on DNA Analysis
      Methods with modifications necessary for validation of nonhuman qPCR assays. All
      assays demonstrated the specificity, sensitivity, stability, reproducibility,
      accuracy, and precision required for forensic casework. The application of these
      assays to animal forensic DNA analysis has both conserved laboratory resources
      and improved genotyping results.

PMID- 21070240
TI  - Protein kinase C activity regulates D-serine availability in the brain.
AB  - D-serine is a co-agonist of NMDA receptor (NMDAR) and plays important roles in
      synaptic plasticity mechanisms. Serine racemase (SR) is a brain-enriched enzyme
      that converts L-serine to D-serine. SR interacts with the protein interacting
      with C-kinase 1 (PICK1), which is known to direct protein kinase C (PKC) to its
      targets in cells. Here, we investigated whether PKC activity regulates SR
      activity and D-serine availability in the brain. In vitro, PKC phosphorylated SR
      and decreased its activity. PKC activation increased SR phosphorylation in serine
      residues and reduced D-serine levels in astrocyte and neuronal cultures.
      Conversely, PKC inhibition decreased basal SR phosphorylation and increased
      cellular D-serine levels. In vivo modulation of PKC activity regulated both SR
      phosphorylation and D-serine levels in rat frontal cortex. Finally, rats that
      completed an object recognition task showed decreased SR phosphorylation and
      increased D-serine/total serine ratios, which was markedly correlated with
      decreased PKC activity in both cortex and hippocampus. Results indicate that PKC
      phosphorylates SR in serine residues and regulates D-serine availability in the
      brain. This interaction may be relevant for the regulation of physiological and
      pathological mechanisms linked to NMDAR function.

PMID- 21070241
TI  - Cold pre-conditioning neuroprotection depends on TNF-alpha and is enhanced by
      blockade of interleukin-11.
AB  - Cold pre-conditioning reduces subsequent brain injury in small animals but the
      underlying mechanisms remain undefined. As hypothermia triggers systemic
      macrophage tumor necrosis factor alpha (TNF-alpha) production and other neural
      pre-conditioning stimuli depend on this cytokine, we reasoned that microglia and
      TNF-alpha would be similarly involved with cold pre-conditioning neuroprotection.
      Also, as slice cultures closely approximate their in vivo counterpart and include
      quiescent microglia, we used rat hippocampal slice cultures to confirm this
      hypothesis. Furthermore, inflammatory cytokine gene screening with subsequent PCR
      and immunostaining confirmation of targeted mRNA and related protein changes
      showed that cold pre-conditioning triggered a significant rise in TNF-alpha that
      localized to microglia and a significant rise in interleukin (IL)-11 that
      localized mainly to hippocampal pyramidal neurons and, more rarely, astrocytes.
      Importantly, co-stimulation with cold and IL-11, an anti-inflammatory cytokine
      that inhibits TNF-alpha expression, abrogated the otherwise evident protection.
      Instead, cold pre-conditioning coupled with blockade of IL-11 signaling further
      enhanced neuroprotection from that seen with cold pre-conditioning alone. Thus,
      physiological activation of brain pro-inflammatory cytokine signaling, and its
      amplification by inhibition of coincident anti-inflammatory cytokine signaling,
      may be opportune targets for the development of novel therapeutics that can mimic
      the protection seen in cold pre-conditioning.

PMID- 21070243
TI  - Pediatric patients' orthodontic treatment need, quality of life, and smiling
      patterns -- an analysis of patient, parent, and provider responses.
AB  - OBJECTIVES: The objectives of this study is to explore the relationship between
      pediatric patients' orthodontic treatment need, the patients' assessments of
      their smile-related quality of life (QoL), their parents' proxy assessment of
      their child's QoL and own assessments of their child's smile, and the patients'
      objectively assessed smiling patterns. METHODS: Survey data were collected from
      102 patients (53 boys/49 girls; age range: 9-13 years) and their parents.
      Orthodontic treatment need was assessed with the Index of Complexity, Outcome,
      and Need (ICON). Smiling patterns were determined by videotaping patients' smiles
      while they watched a cartoon. Thirty predetermined sections of these tapes were
      then assessed by two independent raters to measure the patients' smiling
      patterns. RESULTS: The aesthetic component and total ICON scores correlated with
      the patients' smile-related QoL (r = 0.25; P = 0.014/r = 0.23; P = 0.024),
      parental proxy assessments of the child's smile-related QoL (r = 0.29; P= 0.004/r
      = 0.26; P= 0.009), the parents' own assessments of their child's smile (r= 0.32;
      P= 0.002/ r = 0.29; P = 0.005), and the number of negative adjectives chosen by
      the parents to describe their child's smile (r= 0.32; P = 0.002/r = 0.30; P =
      0.004). Although the smiling patterns were correlated with the patients' smile
      related QoL responses (height of smile: r = 0.29; P = 0.005/number of teeth
      shown: r = 0.30; P = 0.004), the ICON scores were not correlated with the
      patients' smiling patterns. CONCLUSIONS: Objectively assessed orthodontic
      treatment need correlates with the patients' and parents' assessments of the
      child's smile-related QoL scores. However, while objective smiling patterns are
      related with the patients' smile-related QoL, they are not correlated with the
      patients' orthodontic treatment need.

PMID- 21070242
TI  - Density and function of central serotonin (5-HT) transporters, 5-HT1A and 5-HT2A
      receptors, and effects of their targeting on BTBR T+tf/J mouse social behavior.
AB  - BTBR mice are potentially useful tools for autism research because their behavior
      parallels core social interaction impairments and restricted-repetitive
      behaviors. Altered regulation of central serotonin (5-HT) neurotransmission may
      underlie such behavioral deficits. To test this, we compared 5-HT transporter
      (SERT), 5-HT(1A) and 5-HT(2A) receptor densities among BTBR and C57 strains.
      Autoradiographic [(3) H] cyanoimipramine (1 nM) binding to SERT was 20-30% lower
      throughout the adult BTBR brain as compared to C57BL/10J mice. In hippocampal
      membrane homogenates, [(3) H] citalopram maximal binding (B(max) ) to SERT was 95
      +/- 13 fmol/mg protein in BTBR and 171 +/- 20 fmol/mg protein in C57BL/6J mice,
      and the BTBR dissociation constant (K(D) ) was 2.0 +/- 0.3 nM versus 1.1 +/- 0.2
      in C57BL/6J mice. Hippocampal 5-HT(1A) and 5-HT(2A) receptor binding was similar
      among strains. However, 8-OH-DPAT-stimulated [(35) S] GTPgammaS binding in the
      BTBR hippocampal CA(1) region was 28% higher, indicating elevated 5-HT(1A)
      capacity to activate G-proteins. In BTBR mice, the SERT blocker, fluoxetine (10
      mg/kg) and the 5-HT(1A) receptor partial-agonist, buspirone (2 mg/kg) enhanced
      social interactions. The D(2) /5-HT(2) receptor antagonist, risperidone (0.1
      mg/kg) reduced marble burying, but failed to improve sociability. Overall,
      altered SERT and/or 5-HT(1A) functionality in hippocampus could contribute to the
      relatively low sociability of BTBR mice.

PMID- 21070244
TI  - Oral health content of early education and child care regulations and standards.
AB  - OBJECTIVE: Almost two out of every three US children younger than five receive
      child care from someone other than their parents. Health promotion in early
      education and child care (EECC) programs can improve the general health of
      children and families, but little is known about the role of these programs in
      oral health. We identified U.S. EECC program guidelines and assessed their oral
      health recommendations for infants and toddlers. METHODS: State licensing
      regulations were obtained from the National Resource Center for Health and Safety
      in Child Care's online database. Professional standards were identified through a
      search of PubMed, early childhood organizations' websites, and early childhood
      literature. All EECC guidelines were reviewed for key terms related to oral
      health promotion in children and summarized by domains. RESULTS: Thirty-six
      states include oral health in their licensing regulations, but recommendations
      are limited and most often address the storage of toothbrushes. Eleven sets of
      standards were identified, four of which make recommendations about oral health.
      Standards from the American Academy of Pediatrics/American Public Health
      Association (AAP/APHA) and the Office of Head Start (OHS) provide the most
      comprehensive oral health recommendations regarding screening and referral,
      classroom activities, and education. CONCLUSIONS: Detailed guidelines for oral
      health practices exist but they exhibit large variation in number and content.
      States can use the comprehensive standards from the AAP/APHA and OHS to inform
      and strengthen the oral health content of their licensing regulations. Research
      is needed to determine compliance with regulations and standards, and their
      effect on oral health.

PMID- 21070245
TI  - Functional characterization of a plant-like sucrose transporter from the
      beneficial fungus Trichoderma virens. Regulation of the symbiotic association
      with plants by sucrose metabolism inside the fungal cells.
AB  - * Sucrose exuded by plants into the rhizosphere is a crucial component for the
      symbiotic association between the beneficial fungus Trichoderma and plant roots.
      In this article we sought to identify and characterize the molecular basis of
      sucrose uptake into the fungal cells. * Several bioinformatics tools enabled us
      to identify a plant-like sucrose transporter in the genome of Trichoderma virens
      Gv29-8 (TvSut). Gene expression profiles in the fungal cells were analyzed by
      Northern blotting and quantitative real-time PCR (qRT-PCR). Biochemical and
      physiological studies were conducted on Gv29-8 and fungal strains impaired in the
      expression of TvSut. * TvSut exhibits biochemical properties similar to those
      described for sucrose symporters from plants. The null expression of tvsut caused
      a detrimental effect on fungal growth when sucrose was the sole source of carbon
      in the medium, and also affected the expression of genes involved in the
      symbiotic association. * Similar to plants, T. virens contains a highly specific
      sucrose/H(+) symporter that is induced in the early stages of root colonization.
      Our results suggest an active sucrose transference from the plant to the fungal
      cells during the beneficial associations. In addition, our expression experiments
      suggest the existence of a sucrose-dependent network in the fungal cells that
      regulates the symbiotic association.

PMID- 21070246
TI  - Effects of multiple climate change factors on the tall fescue-fungal endophyte
      symbiosis: infection frequency and tissue chemistry.
AB  - * Climate change (altered CO(2) , warming, and precipitation) may affect plant
      microbial interactions, such as the Lolium arundinaceum-Neotyphodium coenophialum
      symbiosis, to alter future ecosystem structure and function. * To assess this
      possibility, tall fescue tillers were collected from an existing climate
      manipulation experiment in a constructed old-field community in Tennessee (USA).
      Endophyte infection frequency (EIF) was determined, and infected (E+) and
      uninfected (E-) tillers were analysed for tissue chemistry. * The EIF of tall
      fescue was higher under elevated CO(2) (91% infected) than with ambient CO(2)
      (81%) but was not affected by warming or precipitation treatments. Within E+
      tillers, elevated CO(2) decreased alkaloid concentrations of both ergovaline and
      loline, by c. 30%; whereas warming increased loline concentrations 28% but had no
      effect on ergovaline. Independent of endophyte infection, elevated CO(2) reduced
      concentrations of nitrogen, cellulose, hemicellulose, and lignin. * These results
      suggest that elevated CO(2) , more than changes in temperature or precipitation,
      may promote this grass-fungal symbiosis, leading to higher EIF in tall fescue in
      old-field communities. However, as all three climate factors are likely to change
      in the future, predicting the symbiotic response and resulting ecological
      consequences may be difficult and dependent on the specific atmospheric and
      climatic conditions encountered.

PMID- 21070247
TI  - Early life nutrition and metabolic programming.
AB  - Research investigating the early programming of adult metabolic disease has in
      recent years provided much mechanistic insight into how the early environment
      impacts on long-term health. It includes studies addressing the roles of
      intrauterine nutrient availability, which is determined by maternal nutrition,
      maternal exposure to oxygen, toxic events, and infection; the placental
      interface; and also the early postnatal environment. This review will explore the
      epidemiological evidence for programming of metabolic disease and provide an
      overview of the various studies using animals to model metabolic phenotypic
      outcome. It will also discuss evidence for the proposed molecular mechanisms and
      the potential for intervention.

PMID- 21070248
TI  - CNS leptin and insulin action in the control of energy homeostasis.
AB  - The obesity and diabetes pandemics have made it an urgent necessity to define the
      central nervous system (CNS) pathways controlling body weight, energy
      expenditure, and fuel metabolism. The pancreatic hormone insulin and the adipose
      tissue-derived leptin are known to act on diverse neuronal circuits in the CNS to
      maintain body weight and metabolism in a variety of species, including humans.
      Because these homeostatic circuits are disrupted during the development of
      obesity, the pathomechanisms leading to CNS leptin and insulin resistance are a
      focal point of research. In this review, we summarize the recent findings
      concerning the mechanisms and novel neuronal mediators of both insulin and leptin
      action in the CNS.

PMID- 21070249
TI  - Hypothalamic control of energy metabolism via the autonomic nervous system.
AB  - The hypothalamic control of hepatic glucose production is an evident aspect of
      energy homeostasis. In addition to the control of glucose metabolism by the
      circadian timing system, the hypothalamus also serves as a key relay center for
      (humoral) feedback information from the periphery, with the important role for
      hypothalamic leptin receptors as a striking example. The hypothalamic biological
      clock uses its projections to the preautonomic hypothalamic neurons to control
      the daily rhythms in plasma glucose concentration, glucose uptake, and insulin
      sensitivity. Euglycemic, hyperinsulinemic clamp experiments combined with either
      sympathetic-, parasympathetic-, or sham-denervations of the autonomic input to
      the liver have further delineated the hypothalamic pathways that mediate the
      control of the circadian timing system over glucose metabolism. In addition,
      these experiments clearly showed both that next to the biological clock
      peripheral hormones may "use" the preautonomic neurons in the hypothalamus to
      affect hepatic glucose metabolism, and that similar pathways may be involved in
      the control of lipid metabolism in liver and white adipose tissue.

PMID- 21070251
TI  - Increased oxidative DNA damage in patients with alcohol dependence and its
      correlation with alcohol withdrawal severity.
AB  - BACKGROUND: Chronic and excessive alcohol consumption enhances the formation of
      reactive oxygen species (ROS) and ethanol-derived free radicals. 8-Hydroxy-2'
      deoxyguanosine (8-OHdG) is a marker to estimate ROS-induced DNA damage. The study
      objective was to compare serum 8-OHdG levels between patients with alcohol
      dependence and healthy controls and to investigate the correlation between this
      marker and the severity of alcohol withdrawal syndrome (AWS). METHODS: We
      recruited 79 patients with alcohol dependence and 63 healthy control subjects.
      The severity of AWS was evaluated using the Chinese version of the revised
      Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar-C) every 8
      hours. Levels of 8-OHdG, malondialdehyde (MDA), and other biologic indexes were
      assayed at baseline for patient and control groups, and after 1-week
      detoxification for the patient group. RESULTS: The 8-OHdG and MDA levels in the
      alcoholic group were significantly higher than those in the control group (0.34
      vs. 0.27 ng/ml and 13.5 vs. 10.1 MUM, respectively). Both 8-OHdG and MDA were
      significantly correlated with the highest CIWA-Ar-C (correlation coefficient =
      0.39, p < 0.001 and 0.26, p = 0.02, respectively). In linear regression analysis,
      only 8-OHdG level was significantly correlated with the highest CIWA-Ar, but not
      MDA level (regression coefficient beta = 0.33, p = 0.003 and 0.17, p = 0.12,
      respectively). MDA, but not 8-OHdG levels, significantly decreased after 1 week
      of detoxification. CONCLUSIONS: These results indicate that our alcohol-dependent
      individuals are vulnerable to excessive production of free radicals. Notably, the
      oxidative DNA damage persisted after 1-week detoxification. The AWS severity was
      correlated with the increase in oxidative stress, particularly the 8-OHdG levels.
      The impact of sustained abstinence in alcoholic patients needs to be investigated
      in future studies.

PMID- 21070250
TI  - The influence of selection for ethanol withdrawal severity on traits associated
      with ethanol self-administration and reinforcement.
AB  - BACKGROUND: Several meta-analyses indicate that there is an inverse genetic
      correlation between ethanol preference drinking and ethanol withdrawal severity,
      but limited work has characterized ethanol consumption in 1 genetic animal model,
      the Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mouse lines selected for
      severe or mild ethanol withdrawal, respectively. METHODS: We determined whether
      line differences existed in: (i) operant self-administration of ethanol during
      sucrose fading and under different schedules of reinforcement, followed by
      extinction and reinstatement of responding with conditioned cues and (ii) home
      cage drinking of sweetened ethanol and the development of an alcohol deprivation
      effect (ADE). RESULTS: Withdrawal Seizure-Prone-1 mice consumed more ethanol than
      WSR-1 mice under a fixed ratio (FR)-4 schedule as ethanol was faded into the
      sucrose solution, but this line difference dissipated as the sucrose was faded
      out to yield an unadulterated 10% v/v ethanol solution. In contrast, WSR-1 mice
      consumed more ethanol than WSP-1 mice when a schedule was imposed that
      procedurally separated appetitive and consummatory behaviors. After both lines
      achieved the extinction criterion, reinstatement was serially evaluated following
      oral ethanol priming, light cue presentation, and a combination of the 2 cues.
      The light cue produced maximal reinstatement of responding in WSP-1 mice, whereas
      the combined cue was required to produce maximal reinstatement of responding in
      WSR-1 mice. There was no line difference in the home cage consumption of a
      sweetened ethanol solution over a period of 1 month. Following a 2-week period of
      abstinence, neither line developed an ADE. CONCLUSIONS: Although some line
      differences in ethanol self-administration and reinstatement were identified
      between WSP-1 and WSR-1 mice, the absence of consistent divergence suggests that
      the genes underlying these behaviors do not reliably overlap with those that
      govern withdrawal severity.

PMID- 21070253
TI  - The risk of ionizing radiation in electrophysiology studies and ablations.

PMID- 21070254
TI  - Unusual response to His-synchronous ventricular extra-stimulation during a
      supraventricular tachycardia: what is the mechanism?

PMID- 21070252
TI  - Administration of memantine during ethanol withdrawal in neonatal rats: effects
      on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell
      loss.
AB  - BACKGROUND: Alcohol consumption during pregnancy can damage the developing fetus,
      illustrated by central nervous system dysfunction and deficits in motor and
      cognitive abilities. Binge drinking has been associated with an increased risk of
      fetal alcohol spectrum disorders, likely due to increased episodes of ethanol
      withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA)
      receptor during ethanol withdrawal leads to excitotoxic cell death in the
      developing brain. Consistent with this, administration of NMDA receptor
      antagonists (e.g., MK-801) during withdrawal can attenuate ethanol's teratogenic
      effects. The aim of this study was to determine whether administration of
      memantine, an NMDA receptor antagonist, during ethanol withdrawal could
      effectively attenuate ethanol-related deficits, without the adverse side effects
      associated with other NMDA receptor antagonists. METHODS: Sprague-Dawley pups
      were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on
      postnatal day 6, a period of brain development equivalent to a portion of the 3rd
      trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0,
      10, or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor
      coordination was tested on a parallel bar task and the total number of cerebellar
      Purkinje cells was estimated using unbiased stereology. RESULTS: Alcohol exposure
      induced significant parallel bar motor incoordination and reduced Purkinje cell
      number. Memantine administration significantly attenuated both ethanol-associated
      motor deficits and cerebellar cell loss in a dose-dependent manner. CONCLUSIONS:
      Memantine was neuroprotective when administered during ethanol withdrawal. These
      data provide further support that ethanol withdrawal contributes to fetal alcohol
      spectrum disorders.

PMID- 21070255
TI  - An animal model for ectopy-induced cardiomyopathy.
AB  - BACKGROUND: Ectopy-induced cardiomyopathy is an increasingly recognized cause of
      reversible left ventricular (LV) dysfunction. The underlying mechanisms remain
      unknown. Our goal was to create an animal model for ectopy-induced
      cardiomyopathy. METHODS: Eleven mongrel dogs underwent the implantation of a dual
      chamber pacemaker. Four dogs served as the control group and seven as the paced
      group. In the paced group, the pacemaker was connected to two endocardial right
      ventricular leads, one inserted into the atrial port and the other one into the
      ventricular port with an atrioventricular delay adjusted to ensure the presence
      of coupled pacing simulating ventricular bigeminy. Echocardiographic measurements
      of LV size (LV end-diastolic diameter [LV-EDD], LV end-systolic diameter [LV
      ESD]), LV ejection fraction (LVEF), and mitral regurgitation (MR) were obtained
      at baseline and after 4 weeks of monitoring or pacing in all dogs except one who
      had lead dislodgement. RESULTS: In the control group (n = 4), no significant
      changes in LV dimensions or function were noted. In the paced group (n = 6), LV
      EDD and LV-ESD increased from 3.58 +/- 0.65 cm and 2.47 +/- 0.55 cm to 4.15 +/-
      0.59 cm and 3.21 +/- 0.47 cm, respectively (P < 0.01). In addition, LVEF
      decreased from 60 +/- 7% to 46 +/- 9% (P < 0.05). No changes in MR were noted.
      CONCLUSION: We have shown that coupled pacing simulating ventricular bigeminy was
      feasible and resulted in increased LV dimensions and decreased LV function. By
      controlling the percentage of pacing, the coupling interval and the location of
      the pacing lead, this new model will allow the assessment of the relative roles
      of these variables in the development of ectopy-induced cardiomyopathy.

PMID- 21070256
TI  - Meta-analysis to assess the appropriate endpoint for slow pathway ablation of
      atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: There are little data on the appropriate endpoint for slow pathway
      ablation that balances acceptable procedural times, recurrence rates, and
      complication rates. This study compared recurrence rates of three commonly
      utilized endpoints of slow pathway ablation for atrioventricular nodal reentrant
      tachycardia (AVNRT). METHODS: We performed a meta-analysis of AVNRT slow pathway
      ablation cohorts by searching electronic databases, the Internet, and conference
      proceedings. Inclusion criteria were age >18 years, >20 human subjects per study,
      primary AVNRT ablation, English language publication, and >1 month of follow-up.
      Data were analyzed with a fixed-effects model using Comprehensive Meta-Analysis
      software version 2.2.046 (Biostat, Englewood, NJ, USA). RESULTS: We included 10
      studies encompassing 1,204 patients with a mean age of 41-53 years. Endpoints
      were complete slow pathway ablation, residual jump only, and single remaining
      echo beat. Pooled estimates revealed 28 of 641 patients (4.4%) with complete slow
      pathway ablation, 13 of 192 patients (6.8%) with a residual jump only, and 24 of
      371 patients (6.5%) with one echo had recurrences. With uniform isoproterenol use
      after ablation, there was no significant difference in recurrence rates among the
      endpoints. However, when isoproterenol was utilized after ablation only if needed
      to induce AVNRT before ablation, a significantly higher recurrence rate occurred
      in patients with a residual jump (P = 0.002), a single echo (P = 0.003), or the
      combined group of a residual jump and/or one echo (P = 0.001). CONCLUSIONS:
      Isoproterenol should be used routinely after slow pathway modification, when a
      residual jump and/or single echo remain.

PMID- 21070257
TI  - Long-term outcomes after pocket or scar revision and reimplantation of pacemakers
      with preerosion.
AB  - INTRODUCTION: Cardiac pacemakers with preerosion are often reimplanted.
      Preerosion may be caused by an evolving local infectious process affecting the
      entire pacing system or by mechanical migration of the device causing ischemic
      necrosis of the skin tissues. We examined the long-term outcome of 33 patients
      who underwent pocket or scar revision and submuscular reimplantation of cardiac
      pacemakers in our institution. METHODS: Before undergoing pocket or scar revision
      and reimplantation, all patients (1) had negative serial blood cultures, (2) had
      no vegetation on transesophageal echocardiography, (3) had a normal blood C
      reactive protein concentrations, (4) were afebrile, (5) had no cutaneous
      breakthrough, and (6) presented with preerosion of the pulse generator or
      granulomatous-like scar abnormality. RESULTS: THE mean follow-up was 37 +/- 12
      months. Among 16 patients presenting with preerosion associated with signs of
      local cutaneous inflammation, 62.5% developed an infection of the pacing system
      requiring later explantation. Of eight patients presenting initially with
      migration of the pulse generator and mechanical protrusion, none required
      subsequent explantation of the system. Among nine patients presenting initially
      with granulomatous-like scar abnormalities, 55.6% underwent explantation of the
      pacing system during follow-up for management of documented local infection.
      CONCLUSIONS: The reimplantation of pulse generators with preerosion in the
      presence of local inflammatory manifestations or granulomatous-like changes of
      the scar is complicated by documented cardiac pacemaker infection in >50% of
      cases. In these patients, the explantation of the pacing system is recommended
      before the development of prognostically much more serious spread of infection to
      the leads and cardiac tissues.

PMID- 21070258
TI  - Safety and performance of a system specifically designed for selective site
      pacing.
AB  - INTRODUCTION: In the right ventricle, selective site pacing (SSP) has been shown
      to avoid detrimental hemodynamic effects induced by right ventricular apical
      pacing and, in the right atrium, to prevent the onset of atrial fibrillation and
      to slow down disease progression. The purpose of our multicenter observational
      study was to describe the use of a transvenous 4-French catheter-delivered lead
      for SSP in the clinical practice of a large number of centers. METHODS: We
      enrolled 574 patients in whom an implantable device was indicated. In all
      patients, SSP was achieved by using the Select Secure SystemTM (Medtronic Inc.,
      Minneapolis, MN, USA). RESULTS: In 570 patients, the lead was successfully
      implanted. In 125 patients, atrial SSP was performed: in 75 (60%) the lead was
      placed in the interatrial septum, in 31 (25%) in the coronary sinus ostium, and
      in 19 (15%) in the Bachman bundle. Ventricular SSP was undertaken in 138
      patients: in 105 (76%) the high septal right ventricular outflow tract (RVOT)
      position was paced, in seven (5%) the high free-wall RVOT, in 25 (18%) the low
      septal RVOT, and in one (1%) the low free-wall RVOT. In the remaining 307
      patients, the His zone was paced: in 87 (28%) patients, direct His-bundle pacing
      and in 220 (72%) patients para-hisian pacing was achieved. Adequate pacing
      parameters and a lead-related complication rate of 2.6% were recorded during a
      follow-up of 20 +/- 10 months. CONCLUSIONS: Our results demonstrated that many
      sites, in the right atrium, in the right ventricle, and in His-bundle region, can
      be paced using the Select Secure SystemTM.

PMID- 21070259
TI  - Learning curve for zero-fluoroscopy catheter ablation of AVNRT: early versus late
      experience.
AB  - INTRODUCTION/BACKGROUND: Three-dimensional catheter navigation systems are being
      utilized more frequently to minimize or eliminate fluoroscopy during catheter
      ablation. We reviewed our learning curve for a zero-fluoroscopy approach over a
      32-month period. METHODS: Data were obtained retrospectively from 62 consecutive
      patients who underwent cryoablation of AVNRT without the use of fluoroscopy from
      December 2005 to August 2008. The early era was defined as the first 12 months of
      procedures (December 2005-December 2006, n = 27) and the recent era thereafter
      (January 2007-August 2008, n = 35). RESULTS: In the early era, acute success was
      achieved in 100% of patients, compared to 97% in the recent era. There were no
      significant complications in either group. Transient AV block was seen
      frequently; however, this always resolved quickly. Average procedure time for the
      early era was 202 minutes (100-419 minutes) compared to 160 minutes (78-332
      minutes) in the recent era (P = 0.01). Recurrence rates were 15% and 8% for the
      early and recent era, respectively. CONCLUSION: Procedure time significantly
      shortens as a function of experience. After an adequate learning curve, the
      procedure can be performed in a very acceptable amount of time.

PMID- 21070260
TI  - Early abrasion of outer silicone insulation after intracardiac lead friction in a
      patient with cardiac device-related infective endocarditis.
AB  - We present a case of a 76-year-old woman on a permanent pacing device, with early
      abrasion of silicone endocardial lead insulations complicated by lead-dependent
      infective endocarditis 13 months after placement of an implantable pulse
      generator. The leads were removed using transvenous technique with direct
      traction, and with no additional tools. In the previous report, a set of
      additional tools was used, and therefore intraoperative endocardial lead
      abrasions or mechanical damage of leads could have not been excluded. The present
      case undoubtedly proves that the friction of leads against each other may result
      in abrasions of insulation of the intracardiac section of the lead.

PMID- 21070261
TI  - Methods for examination an explanted coronary sinus lead stabilized with a
      coronary stent.
AB  - The aim of our investigation was to test the suitability of a novel method for
      the analysis of the integrity of an explanted pacemaker lead stabilized by a
      stent. A coronary sinus lead has been explanted 27 months after implantation and
      has been examined by optical-, confocal-, x-ray-, and scanning electron
      microscopy. Several surface injuries were found on the insulation. Based on the
      surface characteristics, it is possible to define and differentiate the source of
      damages as well as to measure the extent of injuries. Impedance of the explanted
      lead has also been measured and electronic integrity has been verified.

PMID- 21070262
TI  - Lead fracture and free-wall perforation in a patient with an implantable
      cardioverter-defibrillator.
AB  - Intracardiac lead fracture or free-wall perforation is a rare complication of
      implantable defibrillators. Complete disconnection of the fractured electrode has
      not been reported yet. Here, we report a case of lead fracture/disconnection and
      free-wall perforation, which occurred consecutively in a patient.

PMID- 21070263
TI  - Isolated left atrial standstill identified during catheter ablation.
AB  - This report describes the incidental finding of complete left atrial standstill
      during successful ablation of a right-sided atrial tachycardia in a patient with
      severe dilated cardiomyopathy and a history of extensive catheter ablation within
      the left atrium.

PMID- 21070264
TI  - Evaluation of an arthroscopic approach for transection of the equine collateral
      sesamoidean ligament.
AB  - OBJECTIVE: To evaluate: (1) an arthroscopic technique for transection of the
      collateral sesamoidean ligament (CSL); and (2) the healing response using
      magnetic resonance (MR) and microscopic examination. STUDY DESIGN: Experimental
      study. ANIMALS: Adult horses (n=6). METHODS: Six sound horses with normal front
      foot radiographic and MR examinations were used. Lameness examination was
      performed before surgery and monthly for 12 months. Front foot radiography was
      performed at 180 and 360 days after surgery. Front foot MR was performed before,
      and at 7, 90, 180, and 360 days after surgery. Arthroscopic CSL desmotomy was
      performed on 1 forelimb. Gross and microscopic examination was performed on the
      CSL from both forelimbs at 360 days after surgery. Lameness scores were compared
      over time using the nonparametric Friedman's test for paired groups. CSL
      measurements were compared using paired t-tests with a 2-tailed significance
      level of P<.05. RESULTS: Radiographs remained normal throughout study period.
      Surgery resulted in lameness on the operated limb for up to 2 months, after which
      all horses returned to soundness. CSL transection was confirmed during
      arthroscopy and with MR examination 7 days after surgery. Gross and microscopic
      evaluation confirmed ligament healing. CONCLUSIONS: CSL desmotomy resulted in
      short-term lameness after surgery followed by healing of the CSL confirmed by
      gross and microscopic analysis.

PMID- 21070265
TI  - Does the degree of preoperative subluxation or soft tissue tension affect the
      incidence of postoperative luxation in dogs after total hip replacement?
AB  - OBJECTIVE: To investigate whether preexisting coxofemoral subluxation/luxation
      predisposes to postoperative total hip replacement (THR) luxation. STUDY DESIGN:
      Case series. ANIMALS: Dogs (n=100) that had cemented THR (n=109); 23 normal
      controls. METHODS: A preliminary study was performed to validate our methods of
      assessing luxation and laxity by comparing dogs with severe hip dysplasia with a
      control population of normal dogs. For the main study, the records and
      radiographs of all dogs that had primary THR were reviewed. Measurements taken
      from preoperative radiographs to quantify hip subluxation/laxity included the
      Norberg angle, subluxation index, and 2 new measures: acetabular depth ratio
      (ADR) and dorsal acetabular rim ratio (DARR). Differences between groups that had
      luxation within 8 weeks and those that did not were investigated. RESULTS:
      Postoperative luxation occurred in 13 dogs (12%) within 8 weeks of surgery.
      Luxation was significantly associated with various measurements (including
      Norberg angle, ADR, DARR) thought to reflect degree of subluxation/soft tissue
      tension. CONCLUSION: Luxation after canine THR is a multifactorial problem but
      preexisting subluxation/soft tissue laxity is a significant risk factor for this
      complication.

PMID- 21070266
TI  - Antimicrobial efficacy of lactoferrin, its amidated and pepsin-digested
      derivatives, and their combinations, on Escherichia coli O157:H7 and Serratia
      liquefaciens.
AB  - AIMS: To evaluate the in vitro bactericidal efficacy of lactoferrin (LF), its
      amidated (AMILF) and pepsin-digested (PDLF) derivatives, and their combinations,
      on Escherichia coli O157:H7 and Serratia liquefaciens. METHODS AND RESULTS: PDLF
      exhibited the most potent bactericidal efficacy on E. coli O157:H7 (>2.5 log(10)
      CFU ml(-1) reduction at concentrations >= 1 mg ml(-1)), and AMILF on Ser.
      liquefaciens (1 log(10) CFU ml(-1) reduction at 0.25-0.50 mg ml(-1)). Some
      combinations of LF with PDLF or AMILF showed a slight synergy on E. coli O157:H7
      and Ser. liquefaciens. However, all combinations of AMILF with PDLF were less
      active than the sum of the individual effects of the two antimicrobials.
      Production of capsular polysaccharide by bacteria might be involved in
      antimicrobial resistance. CONCLUSIONS: Escherichia coli O157:H7 and Ser.
      liquefaciens showed marked differences in the sensitivity to LF and its
      derivatives. E. coli O157:H7 was strongly inhibited by PDLF, whereas the effect
      of LF and its derivatives on Ser. liquefaciens was weak to negligible.
      SIGNIFICANCE AND IMPACT OF THE STUDY: PDLF was the most promising of the tested
      antimicrobials on E. coli O157:H7. However, the resistance of Ser. liquefaciens
      to LF and its derivatives hinders their use in the food industry.

PMID- 21070267
TI  - Conventional and molecular methods to detect bacterial pathogens in mussels.
AB  - AIM: To detect Aeromonas spp., Salmonella spp., Vibrio cholerae, Vibrio
      parahaemolyticus and Vibrio vulnificus in mussels and water samples from a
      farming area, conventional and molecular methods were applied to enrichment
      cultures. METHODS AND RESULTS: The aerolysin gene (aero) of Aeromonas spp., the
      invasion plasmid antigen B (ipaB) gene of Salmonella spp., the enterotoxin
      secretion protein (epsM) gene of V. cholerae, the species-specific region of 16S
      rRNA gene of V. vulnificus, the 16S-23S rDNA (IGS) gene of V. parahaemolyticus
      and the pR72H fragment of V. parahaemolyticus were amplified by multiplex
      polymerase chain reaction (PCR) assays on DNA extracted from enrichment cultures.
      The haemolysin gene (tdh) of pathogenic V. parahaemolyticus was also amplified.
      Conventional culture method allowed the isolation of V. parahaemolyticus and V.
      vulnificus from water and mussels. The genes aero, epsM and 16S rRNA of V.
      vulnificus were occasionally detected in the enrichment cultures. In mussels, the
      ipaB and IGS genes were detected from June to September and from April to
      November, respectively. All genes, except aero, were amplified from mussels
      collected in September, when pathogenic V. parahaemolyticus (tdh+) strains were
      also isolated. CONCLUSIONS: Multiplex-PCR assays were more sensitive and faster
      than conventional procedures. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      emphasize the need of an accurate and rapid detection of bacterial pathogens in
      mussels to protect human health.

PMID- 21070268
TI  - Enhancement of docosahexaenoic acid production by Schizochytrium sp. using a two
      stage oxygen supply control strategy based on oxygen transfer coefficient.
AB  - AIMS: To improve the yield and productivity of docosahexaenoic acid (DHA) by
      Schizochytrium sp. in terms of the analysis of microbial physiology. METHODS AND
      RESULTS: A two-stage oxygen supply control strategy, aimed at achieving high
      concentration and high productivity of DHA, was proposed. At the first 40 h, K(L)
      a was controlled at 150.1 h(-1) to obtain high MU for cell growth, subsequently
      K(L) a was controlled at 88.5 h(-1) to maintain high q(p) for high DHA
      accumulation. Finally, the maximum lipid, DHA content and DHA productivity
      reached 46.6, 17.7 g l(-1) and 111 mg l(-1) h(-1), which were 43.83%, 63.88% and
      32.14% over the best results controlled by constant K(L) a. CONCLUSIONS: This
      paper described a two-stage oxygen supply control strategy based on the kinetic
      analysis for efficient DHA fermentation by Schizochytrium sp. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study showed the advantage of two-stage control
      strategy in terms of microbial physiology. As K(L) a is a scaling-up parameter,
      the idea developed in this paper could be scaled-up to industrial process and
      applied to other industrial biotechnological processes to achieve both high
      product concentration and high productivity.

PMID- 21070269
TI  - Genome-wide SNP association-based localization of a dwarfism gene in Friesian
      dwarf horses.
AB  - The recent completion of the horse genome and commercial availability of an
      equine SNP genotyping array has facilitated the mapping of disease genes. We
      report putative localization of the gene responsible for dwarfism, a trait in
      Friesian horses that is thought to have a recessive mode of inheritance, to a 2
      MB region of chromosome 14 using just 10 affected animals and 10 controls. We
      successfully genotyped 34,429 SNPs that were tested for association with dwarfism
      using chi-square tests. The most significant SNP in our study, BIEC2-239376
      (P(2df)=4.54 * 10(-5), P(rec)=7.74 * 10(-6)), is located close to a gene
      implicated in human dwarfism. Fine-mapping and resequencing analyses did not aid
      in further localization of the causative variant, and replication of our findings
      in independent sample sets will be necessary to confirm these results.

PMID- 21070270
TI  - Linkage disequilibrium and historical effective population size in the
      Thoroughbred horse.
AB  - Many genomic methodologies rely on the presence and extent of linkage
      disequilibrium (LD) between markers and genetic variants underlying traits of
      interest, but the extent of LD in the horse has yet to be comprehensively
      characterized. In this study, we evaluate the extent and decay of LD in a sample
      of 817 Thoroughbreds. Horses were genotyped for over 50,000 single nucleotide
      polymorphism (SNP) markers across the genome, with 34,848 autosomal SNPs used in
      the final analysis. Linkage disequilibrium, as measured by the squared
      correlation coefficient (r(2)), was found to be relatively high between closely
      linked markers (>0.6 at 5 kb) and to extend over long distances, with average
      r(2) maintained above non-syntenic levels for single nucleotide polymorphisms
      (SNPs) up to 20 Mb apart. Using formulae which relate expected LD to effective
      population size (N(e)), and assuming a constant actual population size, N(e) was
      estimated to be 100 in our population. Values of historical N(e), calculated
      assuming linear population growth, suggested a decrease in N(e) since the distant
      past, reaching a minimum twenty generations ago, followed by a subsequent
      increase until the present time. The qualitative trends observed in N(e) can be
      rationalized by current knowledge of the history of the Thoroughbred breed, and
      inbreeding statistics obtained from published pedigree analyses are in agreement
      with observed values of N(e). Given the high LD observed and the small estimated
      N(e), genomic methodologies such as genomic selection could feasibly be applied
      to this population using the existing SNP marker set.

PMID- 21070271
TI  - RT-qPCR comparison of mast cell populations in whole blood from healthy horses
      and those with laminitis.
AB  - Inflammatory damage to the digital laminae, a structure responsible for
      suspension of the distal skeleton within the hoof capsule, results in a painful
      and often life-threatening disease in horses called laminitis. There can be many
      diverse causes of laminitis; however, previous work in the horse has suggested
      that in each case, the inflammation and resulting tissue damage is consistent
      with the action of mediators released from mast cells (MC), as well as the
      downstream consequences of their activation. The recent development of molecular
      genetics tools to characterize cells based on their transcriptional activity
      makes a new approach for measuring MCs possible. Healthy thoroughbred horses from
      a variety of age groups were used to assess the amount of variation in KIT
      (encoding mast cell growth factor receptor) and TPSB2 (encoding mast cell
      tryptase beta 2) gene expression present in the population and to establish
      "normal" values. Horses (n=9) with a wider range of body condition scores (3-8),
      because of a more lax management setting that could predispose them to laminitis,
      had significantly higher KIT expression in circulating peripheral blood cells
      than horses under individualized management conditions (n=10) that produced ideal
      body condition scores (4-6) (mean 2.573-fold, P<0.0005). Likewise, horses
      affected with acute laminitis (n=11) had elevated expression of TPSB2 (2.760
      fold, P=0.0011) relative to control horses (n=15). These data suggest that
      investigation of MC-related genes KIT and TPSB2 may be effective to assay MC
      population and activity. More work is needed to refine the diagnostic criteria to
      better describe at what point MC activation occurs and illustrate the use of gene
      expression assays in clinical cases of laminitis. Additionally, MC activation is
      associated with inflammatory disease in several mammalian species and may prove a
      valuable therapeutic target in the horse.

PMID- 21070272
TI  - Transcription of LINE-derived sequences in exercise-induced stress in horses.
AB  - A large proportion of mammalian genomes is represented by transposable elements
      (TE), most of them being long interspersed nuclear elements 1 (LINE-1 or L1). An
      increased expression of LINE-1 elements may play an important role in cellular
      stress-related conditions exerting drastic effects on the mammalian
      transcriptome. To understand the impact of TE on the known horse transcriptome,
      we masked the horse EST database, pointing out that the amount is consistent with
      other major vertebrates. A previously developed transcript-derived fragments
      (TDFs) dataset, deriving from exercise-stimulated horse peripheral blood
      mononuclear cells (PBMCs), was found to be enriched with L1 (26.8% in terms of
      bp). We investigated the involvement of TDFs in exercise-induced stress through
      bioinformatics and gene expression analysis. Results indicate that LINE-derived
      sequences are not only highly but also differentially expressed during physical
      effort, hinting at interesting scenarios in the regulation of gene expression in
      relation to exercise.

PMID- 21070273
TI  - A genome-wide association study for racing performances in Thoroughbreds
      clarifies a candidate region near the MSTN gene.
AB  - Using 1400 microsatellites, a genome-wide association study (GWAS) was performed
      to identify genomic regions associated with lifetime earnings and performance
      ranks, as determined by the Japan Racing Association (JRA). The minimum
      heritability (h(2) ) was estimated at 7-8% based on the quantitative trait model,
      suggesting that the racing performance is heritable. Following GWAS with
      microsatellites, fine mapping led to identification of three SNPs on ECA18,
      namely, g.65809482T>C (P=1.05E-18), g.65868604G>T (P=6.47E-17), and g.66539967A>G
      (P=3.35E-14) associated with these performance measures. The haplotype of these
      SNPs, together with a recently published nearby SNP, g.66493737C>T (P=9.06E-16)
      in strong linkage disequilibrium, also showed a very clear association with the
      performance (P<1E-05). The candidate genomic region contained eight genes
      annotated by ENSEMBL, including the myostatin gene (MSTN). These findings suggest
      the presence of a gene affecting the racing performance in Thoroughbred
      racehorses in this region on ECA18.

PMID- 21070274
TI  - Refinement of quantitative trait loci on equine chromosome 10 for radiological
      signs of navicular disease in Hanoverian warmblood horses.
AB  - Navicular disease is characterized by a progressive degenerative alteration of
      the equine podotrochlea. In this study, we refined a previously identified
      quantitative trait locus (QTL) on horse chromosome 10 for the abnormal
      development of canales sesamoidales (DCS) of the navicular bone in Hanoverian
      warmblood horses. Genotyping was done in 192 Hanoverian warmblood horses from 17
      paternal half-sib groups. The whole marker set comprised 45 markers including
      seven newly developed microsatellites and 13 single nucleotide polymorphisms
      (SNPs) within positional candidate genes. Chromosome-wide significant QTL were
      confirmed and refined for DCS on horse chromosome (ECA) 10 at 0.16-2.70 Mb and at
      14.45-36.37 Mb. Nine microsatellites and three SNP markers reached the highest
      multipoint Zmeans and LOD scores at 19.34-20.38 Mb and at 23.17-30.73 Mb with
      genome-wide error probabilities of P<0.05. In addition, a significant association
      of a SNP within VSTM1 and a significant haplotype-trait association within IRF3
      could be shown. These results support a possible role of the candidate genes
      VSTM1 and IRF3 within the QTL on ECA10 for DCS. This study is a further step
      towards the identification of the genes responsible for navicular disease in
      Hanoverian warmblood horses.

PMID- 21070275
TI  - Molecular heterogeneity of XY sex reversal in horses.
AB  - Male-to-female 64,XY sex reversal is a frequently reported chromosome abnormality
      in horses. Despite this, the molecular causes of the condition are as yet poorly
      understood. This is partially because only limited molecular information is
      available for the horse Y chromosome (ECAY). Here, we used the recently developed
      ECAY map and carried out the first comprehensive study of the Y chromosome in XY
      mares (n=18). The integrity of the ECAY in XY females was studied by FISH and PCR
      using markers evenly distributed along the euchromatic region. The results showed
      that the XY sex reversal condition in horses has two molecularly distinct forms:
      (i) a Y-linked form that is characterized by Y chromosome deletions and (ii) a
      non-Y-linked form where the Y chromosome of affected females is molecularly the
      same as in normal males. Further analysis of the Y-linked form (13 cases) showed
      that the condition is molecularly heterogeneous: the smallest deletions spanned
      about 21 kb, while the largest involved the entire euchromatic region. Regardless
      of the size, all deletions included the SRY gene. We show that the deletions were
      likely caused by inter-chromatid recombination events between repeated sequences
      in ECAY. Further, we hypothesize that the occurrence of SRY-negative XY females
      in some species (horse, human) but not in others (pig, dog) is because of
      differences in the organization of the Y chromosome. Finally, in contrast to the
      Y-linked SRY-negative form of equine XY sex reversal, the molecular causes of SRY
      positive XY mares (5 cases) remain as yet undefined.

PMID- 21070276
TI  - Genetic diversity in the Maremmano horse and its relationship with other European
      horse breeds.
AB  - The Maremmano is an Italian warmblood horse breed from central Italy. We
      characterized the genetic diversity and the degree of admixture in Maremmano in
      comparison to 14 other European horse breeds using 30 microsatellites. Between
      breed diversity explained about 9 per cent of the total genetic diversity.
      Cluster analysis, genetic distances and genetic differentiation coefficients
      showed a close relationship of Maremmano with Hanoverian and Lusitano in
      accordance with breed history.

PMID- 21070277
TI  - Targets of selection in the Thoroughbred genome contain exercise-relevant gene
      SNPs associated with elite racecourse performance.
AB  - Athletic performance is influenced by a complex interplay among the environment
      and a suite of genes, which contributes to system-wide structure and function. In
      a panel of elite and non-elite Thoroughbred horses (n=148), we genotyped 68 SNPs
      in 17 putative exercise-relevant genes chosen from a genome scan for selection.
      We performed a series of case-control and quantitative association tests for
      relationships with racecourse performance. Thirteen SNPs in nine genes were
      significantly (P<0.05) associated with a performance phenotype. We selected five
      SNPs in four genes (ACSS1, ACN9, COX4I1, PDK4) for validation in an independent
      sample set of elite and non-elite Thoroughbreds (n=130). Two SNPs in the PDK4
      gene were validated (P<0.01) for associations with elite racing performance. When
      all samples were considered together (n=278), the PDK4_ 38973231 SNP was strongly
      associated (P<0.0005) with elite racing performance. Individuals with the A:A and
      A:G genotypes had a 16.2-16.6 lb advantage over G:G individuals in terms of
      handicap rating. Re-sequencing of the PDK4 gene and further genotyping will be
      required to identify the causative variant that is likely influencing exercise
      induced variation in expression of the gene. Notwithstanding, this information
      may be employed as a marker for the selection of racehorses with the genetic
      potential for superior racing ability.

PMID- 21070278
TI  - Genetics of swayback in American Saddlebred horses.
AB  - Extreme lordosis, also called swayback, lowback or softback, can occur as a
      congenital trait or as a degenerative trait associated with ageing. In this
      study, the hereditary aspect of congenital swayback was investigated using whole
      genome association studies of 20 affected and 20 unaffected American Saddlebred
      (ASB) Horses for 48,165 single-nucleotide polymorphisms (SNPs). A statistically
      significant association was identified on ECA20 (corrected P=0.017) for SNP BIEC2
      532523. Of the 20 affected horses, 17 were homozygous for this SNP when compared
      to seven homozygotes among the unaffected horses, suggesting a major gene with a
      recessive mode of inheritance. The result was confirmed by testing an additional
      13 affected horses and 166 unaffected horses using 35 SNPs in this region of
      ECA20 (corrected P=0.036). Combined results for 33 affected horses and 287 non
      affected horses allowed identification of a region of homozygosity defined by
      four SNPs in the region. Based on the haplotype defined by these SNPs, 80% of the
      33 affected horses were homozygous, 21% heterozygous and 9% did not possess the
      haplotype. Among the non-affected horses, 15% were homozygous, 47% heterozygous
      and 38% did not possess the haplotype. The differences between the two groups
      were highly significant (P<0.00001). The region defined by this haplotype
      includes 53 known and predicted genes. Exons from three candidate genes, TRERF1,
      RUNX2 and CNPY3 were sequenced without finding distinguishing SNPs. The mutation
      responsible for swayback may lie in other genes or in regulatory regions outside
      exons. This information can be used by breeders to reduce the occurrence of
      swayback among their livestock. This condition may serve as a model for
      investigation of congenital skeletal deformities in other species.

PMID- 21070279
TI  - Comparative human-horse sequence analysis of the CYP3A subfamily gene cluster.
AB  - Cytochrome P450 enzymes (CYP450s) represent a superfamily of haem-thiolate
      proteins. CYP450s are most abundant in the liver, a major site of drug
      metabolism, and play key roles in the metabolism of a variety of substrates,
      including drugs and environmental contaminants. Interaction of two or more
      different drugs with the same enzyme can account for adverse effects and failure
      of therapy. Human CYP3A4 metabolizes about 50% of all known drugs, but little is
      known about the orthologous CYP450s in horses. We report here the genomic
      organization of the equine CYP3A gene cluster as well as a comparative analysis
      with the human CYP3A gene cluster. The equine CYP450 genes of the 3A family are
      located on ECA 13 between 6.97-7.53 Mb, in a region syntenic to HSA 7 99.05-99.35
      Mb. Seven potential, closely linked equine CYP3A genes were found, in contrast to
      only four genes in the human genome. RNA was isolated from an equine liver
      sample, and the approximately 1.5-kb coding sequence of six CYP3A genes could be
      amplified by RT-PCR. Sequencing of the RT-PCR products revealed numerous hitherto
      unknown single nucleotide polymorphisms (SNPs) in these six CYP3A genes, and one
      6-bp deletion compared to the reference sequence (EquCab2.0). The presence of the
      variants was confirmed in a sample of genomic DNA from the same horse. In
      conclusion, orthologous genes for the CYP3A family exist in horses, but their
      number differs from those of the human CYP3A gene family. CYP450 genes of the
      same family show high homology within and between mammalian species, but can be
      highly polymorphic.

PMID- 21070280
TI  - A genome-wide scan for tying-up syndrome in Japanese Thoroughbreds.
AB  - Tying-up syndrome, also known as recurrent exertional rhabdomyolysis in
      Thoroughbreds, is a common muscle disorder for racehorses. In this study, we
      performed a multipoint linkage analysis using LOKI based on the Bayesian Markov
      chain Monte Carlo method using 5 half-sib families (51 affected and 277
      nonaffected horses in total), and a genome-wide association study (GWAS) using
      microsatellites (144 affected and 144 nonaffected horses) to map candidate
      regions for tying-up syndrome in Japanese Thoroughbreds. The linkage analysis
      identified one strong L-score (82.45) between the loci UCDEQ411 and COR058 (24.9
      27.9 Mb) on ECA12. The GWAS identified two suggestive genomic regions on ECA12
      (24.9-27.8 Mb) and ECA20 (29.3-33.5 Mb). Based on both results, the genomic
      region between UCDEQ411 and TKY499 (24.9-27.8 Mb) on ECA12 was the most
      significant and was considered as a candidate region for tying-up syndrome in
      Japanese Thoroughbreds.

PMID- 21070281
TI  - Fine mapping of a quantitative trait locus for osteochondrosis on horse
      chromosome 2.
AB  - In this study, we refine a quantitative trait locus for equine osteochondrosis
      (OC) on horse chromosome (ECA) 2 to a genome-wide significant interval at 20.08
      30.94 Mb. The marker set contained 27 newly developed microsatellites
      equidistantly distributed over ECA2 and 44 nucleotide polymorphisms, located in
      16 positional candidate genes for OC. Genotyping was performed in 211 Hanoverian
      horses from 14 paternal half-sib groups. A NCDN-associated SNP and haplotype were
      significantly associated with OC in fetlock and/or hock joints. This study is a
      further step towards the identification of genes responsible for OC in horses.

PMID- 21070282
TI  - Interspersed repeats in the horse (Equus caballus); spatial correlations
      highlight conserved chromosomal domains.
AB  - The interspersed repeat content of mammalian genomes has been best characterized
      in human, mouse and cow. In this study, we carried out de novo identification of
      repeated elements in the equine genome and identified previously unknown elements
      present at low copy number. The equine genome contains typical eutherian mammal
      repeats, but also has a significant number of hybrid repeats in addition to clade
      specific Long Interspersed Nuclear Elements (LINE). Equus caballus clade specific
      LINE 1 (L1) repeats can be classified into approximately five subfamilies, three
      of which have undergone significant expansion. There are 1115 full-length copies
      of these equine L1, but of the 103 presumptive active copies, 93 fall within a
      single subfamily, indicating a rapid recent expansion of this subfamily. We also
      analysed both interspersed and simple sequence repeats (SSR) genome-wide, finding
      that some repeat classes are spatially correlated with each other as well as with
      G+C content and gene density. Based on these spatial correlations, we have
      confirmed that recently-described ancestral vs. clade-specific genome territories
      can be defined by their repeat content. The clade-specific Short Interspersed
      Nuclear Element correlations were scattered over the genome and appear to have
      been extensively remodelled. In contrast, territories enriched for ancestral
      repeats tended to be contiguous domains. To determine if the latter territories
      were evolutionarily conserved, we compared these results with a similar analysis
      of the human genome, and observed similar ancestral repeat enriched domains.
      These results indicate that ancestral, evolutionarily conserved mammalian genome
      territories can be identified on the basis of repeat content alone. Interspersed
      repeats of different ages appear to be analogous to geologic strata, allowing
      identification of ancient vs. newly remodelled regions of mammalian genomes.

PMID- 21070283
TI  - Pleiotropic effects of pigmentation genes in horses.
AB  - Horses are valued for the beauty and variety of colouration and coat patterning.
      To date, eleven different genes have been characterized that contribute to the
      variation observed in the horse. Unfortunately, mutations involving pigmentation
      often lead to deleterious effects in other systems, some of which have been
      described in the horse. This review focuses on six such pleiotropic effects or
      associations with pigmentation genes. These include neurological defects (lethal
      white foal syndrome and lavender foal syndrome), hearing defects, eye disorders
      (congenital stationary night blindness and multiple congenital ocular anomalies),
      as well as horse-specific melanoma. The pigmentation phenotype, disorder
      phenotype, mode of inheritance, genetic or genomic methods utilized to identify
      the genes involved and, if known, the causative mutations, molecular interactions
      and other susceptibility loci are discussed. As our understanding of pigmentation
      in the horse increases, through the use of novel genomic tools, we are likely to
      unravel yet unknown pleiotropic effects and determine additional interactions
      between previously discovered loci.

PMID- 21070284
TI  - Genome-wide association analysis of osteochondrosis of the tibiotarsal joint in
      Norwegian Standardbred trotters.
AB  - Osteochondrosis (OC), a disturbance in the process of endochondral ossification,
      is by far the most important equine developmental orthopaedic disease and is also
      common in other domestic animals and humans. The purpose of this study was to
      identify quantitative trait loci (QTL) associated with osteochondrosis dissecans
      (OCD) at the intermediate ridge of the distal tibia in Norwegian Standardbred
      (SB) using the Illumina Equine SNP50 BeadChip whole-genome single-nucleotide
      polymorphism (SNP) assay. Radiographic data and blood samples were obtained from
      464 SB yearlings. Based on the radiographic examination, 162 horses were selected
      for genotyping; 80 of these were cases with an OCD at the intermediate ridge of
      the distal tibia, and 82 were controls without any developmental lesions in the
      joints examined. Genotyped horses descended from 22 sires, and the number of
      horses in each half-sib group ranged from 3 to 14. The population structure
      necessitated statistical correction for stratification. When conducting a case
      control genome-wide association study (GWAS), mixed-model analyses displayed
      regions on chromosomes (Equus callabus chromosome - ECA) 5, 10, 27 and 28 that
      showed moderate evidence of association (P <= 5 * 10(-5); this P-value is
      uncorrected i.e. not adjusted for multiple comparisons) with OCD in the
      tibiotarsal joint. Two SNPs on ECA10 represent the most significant hits
      (uncorrected P=1.19 * 10(-5) in the mixed-model). In the basic association (chi
      square) test, these SNPs achieved statistical significance with the Bonferroni
      correction (P=0.038) and were close in the permuted logistic regression test
      (P=0.054). Putative QTL on ECA 5, 10, 27 and 28 represent interesting areas for
      future research, validation studies and fine mapping of candidate regions.
      Results presented here represent the first GWAS of OC in horses using the
      recently released Illumina Equine SNP50 BeadChip.

PMID- 21070285
TI  - Structural annotation of equine protein-coding genes determined by mRNA
      sequencing.
AB  - The horse, like the majority of animal species, has a limited amount of species
      specific expressed sequence data available in public databases. As a result,
      structural models for the majority of genes defined in the equine genome are
      predictions based on ab initio sequence analysis or the projection of gene
      structures from other mammalian species. The current study used Illumina-based
      sequencing of messenger RNA (RNA-seq) to help refine structural annotation of
      equine protein-coding genes and for a preliminary assessment of gene expression
      patterns. Sequencing of mRNA from eight equine tissues generated 293,758105
      sequence tags of 35 bases each, equalling 10.28 gbp of total sequence data. The
      tag alignments represent approximately 207 * coverage of the equine mRNA
      transcriptome and confirmed transcriptional activity for roughly 90% of the
      protein-coding gene structures predicted by Ensembl and NCBI. Tag coverage was
      sufficient to refine the structural annotation for 11,356 of these predicted
      genes, while also identifying an additional 456 transcripts with exon/intron
      features that are not listed by either Ensembl or NCBI. Genomic locus data and
      intervals for the protein-coding genes predicted by the Ensembl and NCBI
      annotation pipelines were combined with 75,116 RNA-seq-derived transcriptional
      units to generate a consensus equine protein-coding gene set of 20,302 defined
      loci. Gene ontology annotation was used to compare the functional and structural
      categories of genes expressed in either a tissue-restricted pattern or broadly
      across all tissue samples.

PMID- 21070287
TI  - Genomic structure, polymorphism and expression of ACCN1 and ACCN3 genes in the
      horse.
AB  - A category of cation gate proteins was shown to be present in sensory neurons and
      act as receptors of protons present in tissues such as muscles. The Amiloride
      sensitive Cation Channel, Neuronal (ACCN) gene family is known to play a role in
      the transmission of pain through specialized pH sensitive neurons. Muscles from
      horses submitted to strenuous exercises produce lactic acid, which may induce
      variable pain through ACCN differential properties. The sequences of the equine
      cDNAs were determined to be 2.6 kb in length with an open reading frame of 1539
      bp for ACCN1 and 2.1 kb in length with an open reading frame of 1602 bp for
      ACCN3. The ACCN1 gene is 990 kb long and contains 10 exons, and the ACCN3 gene is
      4.2 kb long and contains 11 exons. The equine ACCN1 and ACCN3 genes have an
      ubiquitous expression but ACCN1 is more highly expressed in the spinal cord. We
      identified one alternative ACCN3 splicing variant present in various equine
      tissues. These mRNA variants may encode two different protein isoforms 533 and
      509 amino acids long. Ten single nucleotide polymorphisms (SNPs) were detected
      for ACCN1; five in the coding and five in the non-coding region, with no amino
      acid change, while the three SNPs identified in the coding region of the ACCN3
      gene introduce amino acid changes. The equine in silico promoter sequence reveals
      a structure similar to those of other mammalian species, especially for the ACCN1
      gene.

PMID- 21070286
TI  - IgE, IgGa, IgGb and IgG(T) serum antibody levels in offspring of two sires
      affected with equine recurrent airway obstruction.
AB  - Equine recurrent airway obstruction (RAO) is a chronic lower airway disease of
      the horse caused by hypersensitivity reactions to inhaled stable dust, including
      mould spores such as Aspergillus fumigatus. The goals of this study were to
      investigate whether total serum IgE levels and allergen-specific IgE and IgG
      subclasses are influenced by genetic factors and/or RAO and whether quantitative
      trait loci (QTL) could be identified for these parameters. The offspring of two
      RAO-affected sires (S1: n=56 and S2: n=65) were grouped by stallion and disease
      status, and total serum IgE levels and specific IgE, IgGa, IgGb and IgG(T) levels
      against recombinant Aspergillus fumigatus 7 (rAspf7) were measured by ELISA. A
      panel of 315 microsatellite markers covering the 31 equine autosomes were used to
      genotype the stallions and their offspring. A whole-genome scan using half-sib
      regression interval mapping was performed for each of the IgG and IgE subclasses.
      There was no significant effect of disease status or sire on total IgE levels,
      but there was a significant effect of gender and age. rAspf7-specific IgGa levels
      were significantly higher in RAO-affected than in healthy horses. The offspring
      of S1 had significantly higher rAspf7-specific IgGa and IgE levels than those of
      S2. Five QTLs were significant chromosome-wide (P<0.01). QTLs for rAspf7-specific
      IgGa and IgE were identified on ECA 1, for rAspf7-specific IgGa and IgGb on ECA
      24 and for rAspf7 IgGa on ECA 26. These results provide evidence for effects of
      disease status and genetics on allergen-specific IgGa and IgE.

PMID- 21070288
TI  - Estimated prevalence of the Type 1 Polysaccharide Storage Myopathy mutation in
      selected North American and European breeds.
AB  - The GYS1 gene mutation that is causative of Type 1 Polysaccharide Storage
      Myopathy (PSSM) has been identified in more than 20 breeds of horses. However,
      the GYS1 mutation frequency or Type 1 PSSM prevalence within any given breed is
      unknown. The purpose of this study was to determine the frequency of the GYS1
      mutation and prevalence of genetic susceptibility to Type 1 PSSM in selected
      breeds from Europe and North America. The GYS1 mutation was detected in 11
      breeds, including, in order of increasing allele frequency, Shires, Morgans,
      Appaloosas, Quarter Horses, Paints, Exmoor Ponies, Saxon-Thuringian Coldbloods,
      South German Coldbloods, Belgians, Rhenish German Coldbloods and Percherons. The
      prevalence of genetic susceptibility to Type 1 PSSM in these breeds varied from
      0.5% to 62.4%. The GYS1 mutation was not found in the sampled Thoroughbreds,
      Akhal-Tekes, Connemaras, Clydesdales, Norwegian Fjords, Welsh Ponies, Icelandics,
      Schleswig Coldbloods or Hanoverians, but failure to detect the mutation does not
      guarantee its absence. This knowledge will help breed associations determine
      whether they should screen for the GYS1 mutation and will alert veterinarians to
      a possible differential diagnosis for muscle pain, rhabdomyolysis or gait
      abnormalities.

PMID- 21070289
TI  - Identification of equine major histocompatibility complex haplotypes using
      polymorphic microsatellites.
AB  - A system for identifying equine major histocompatibility complex (MHC) haplotypes
      was developed based on five polymorphic microsatellites located within the MHC
      region on ECA 20. Molecular signatures for 50 microsatellite haplotypes were
      recognized from typing 353 horses. Of these, 23 microsatellite haplotypes were
      associated with 12 established equine leucocyte antigen (ELA) haplotypes in
      Thoroughbreds and Standardbreds. Five ELA serotypes were associated with multiple
      microsatellite subhaplotypes, expanding the estimates of diversity in the equine
      MHC. The strong correlations between serological and microsatellite typing
      demonstrated a linkage to known MHC class I protein polymorphisms and validated
      this assay as a useful supplement to ELA serotyping, and in some applications, a
      feasible alternative method for MHC genotyping in horse families and in
      population studies.

PMID- 21070290
TI  - Identification of the myostatin locus (MSTN) as having a major effect on optimum
      racing distance in the Thoroughbred horse in the USA.
AB  - One hundred and eighty-nine Thoroughbred horses that had won Graded Stakes races
      in North America were genotyped with the Illumina Equine SNP50 bead chip.
      Association tests using PLINK to determine whether any SNPs were associated with
      optimum racing distance (7 furlongs and under compared to 8-10 furlongs)
      identified a locus on ECA18 that was statistically significant (-log 10
      EMP2=1.63) at the genome-wide level following permutation analysis (10,000
      permutations). Bioinformatic analysis revealed that the two ECA18 SNPs with the
      highest statistical significance spanned the MSTN (myostatin) locus. Mutations in
      myostatin in several mammalian species have been associated with increased
      muscling, with a preferential increase in fast glycolytic type IIB fibres, which
      would increase power potential. Thoroughbred horses that race over sprint
      distances, which are 5-7 furlongs, are often characterized by impressive hind
      quarter musculature, strongly suggesting that the association observed between
      the ECA18 SNPs and optimum race distance is mediated through MSTN.

PMID- 21070291
TI  - Morphological variation in the horse: defining complex traits of body size and
      shape.
AB  - Horses, like many domesticated species, have been selected for broad variation in
      skeletal size. This variation is not only an interesting model of rapid
      evolutionary change during domestication, but is also directly applicable to the
      horse industry. Breeders select for complex traits like body size and skeletal
      conformation to improve marketability, function, soundness and performance in the
      show ring. Using a well-defined set of 35 measurements, we have identified and
      quantified skeletal variation in the horse species. We collected measurements
      from 1215 horses representing 65 breeds of diverse conformation such as the
      American Miniature, Shetland Pony, Arabian Horse, Thoroughbred, Shire and
      Clydesdale. Principal components analysis has identified two key dimensions of
      skeletal variation in the horse. Principal component 1 is positively correlated
      with every measurement and quantifies overall body size. Principal component 2
      captures a pattern of bone widths vs. lengths and thus quantifies variation in
      overall bone thickness. By defining these complex skeletal traits, we have
      created a framework for whole genome association studies to identify quantitative
      trait loci that contribute to this variation.

PMID- 21070292
TI  - Microarray analysis after strenuous exercise in peripheral blood mononuclear
      cells of endurance horses.
AB  - It is known that moderate physical activity may have beneficial effects on
      health, whereas strenuous effort induces a state resembling inflammation. The
      molecular mechanisms underlying the cellular response to exercise remain unclear,
      although it is clear that the immune system plays a key role. It has been
      hypothesized that the physio-pathological condition that develops in athletes
      subjected to heavy training is caused by derangement of cellular immune
      regulation. The purpose of the present study was to obtain information on
      endurance horse gene transcription under strenuous conditions and to identify
      candidate genes causing immune system derangement. We performed a wide gene
      expression scan, using microarray technology, on peripheral blood mononuclear
      cells of ten horses chosen from high-level participants in national and
      international endurance races. The use of three different timepoints revealed
      changes in gene expression when post-effort samples (T1, taken immediately after
      the race; and T2, taken 24 h after the race) were compared with basal sample (T0,
      at rest). Statistical analysis showed no differences in gene expression between
      T0 and T2 samples, indicating complete restoration of homeostasis by 24 h after
      racing, whereas T1 showed strong modulation of expression, affecting 132 genes
      (97 upregulated, 35 downregulated). Ingenuity pathway analysis revealed that the
      main mechanisms and biofunctions involved were significantly associated with
      immunological and inflammatory responses. Real-time PCR was performed on 26 gene
      products to validate the array data.

PMID- 21070293
TI  - Mitochondrial DNA insertions in the nuclear horse genome.
AB  - The insertion of mitochondrial DNA in the nuclear genome generates numts, nuclear
      sequences of mitochondrial origin. In the horse reference genome, we identified
      82 numts and showed that the entire horse mitochondrial DNA is represented as
      numts without gross bias. Numts were inserted in the horse nuclear genome at
      random sites and were probably generated during the repair of DNA double-strand
      breaks. We then analysed 12 numt loci in 20 unrelated horses and found that null
      alleles, lacking the mitochondrial DNA insertion, were present at six of these
      loci. At some loci, the null allele is prevalent in the sample analysed,
      suggesting that, in the horse population, the number of numt loci may be higher
      than 82 present in the reference genome. Contrary to humans, the insertion
      polymorphism of numts is extremely frequent in the horse population, supporting
      the hypothesis that the genome of this species is in a rapidly evolving state.

PMID- 21070294
TI  - A conserved segmental duplication within ELA.
AB  - The assembled genomic sequence of the horse major histocompatibility complex
      (MHC) (equine lymphocyte antigen, ELA) is very similar to the homologous human
      HLA, with the notable exception of a large segmental duplication at the boundary
      of ELA class I and class III that is absent in HLA. The segmental duplication
      consists of a ~ 710 kb region of at least 11 repeated blocks: 10 blocks each
      contain an MHC class I-like sequence and the helicase domain portion of a BAT1
      like sequence, and the remaining unit contains the full-length BAT1 gene. Similar
      genomic features were found in other Perissodactyls, indicating an ancient
      origin, which is consistent with phylogenetic analyses. Reverse-transcriptase PCR
      (RT-PCR) of mRNA from peripheral white blood cells of healthy and chronically or
      acutely infected horses detected transcription from predicted open reading frames
      in several of the duplicated blocks. This duplication is not present in the
      sequenced MHCs of most other mammals, although a similar feature at the same
      relative position is present in the feline MHC (FLA). Striking sequence
      conservation throughout Perissodactyl evolution is consistent with a functional
      role for at least some of the genes included within this segmental duplication.

PMID- 21070296
TI  - Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for
      warfarin initiation and titration.
AB  - WHAT IS KNOWN AND OBJECTIVE: Anticoagulation consultations provided by a
      pharmacist-staffed inpatient service, similar to the experience reported in
      outpatient anticoagulation clinics, can potentially improve anticoagulation
      control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching
      hospital in Singapore, pharmacist-managed anticoagulation clinics have been in
      place since 1997. Pharmacist-managed services were extended to inpatient
      consultations in anticoagulation management from April 2006. Our objective was to
      assess the effect of implementing a pharmacist-managed inpatient anticoagulation
      service. METHODS: This was a single-centre cohort study. Baseline data from 1
      January 2006 to 31 March 2006 were collected and compared with post
      implementation data from 1 April 2006 to 31 March 2007. Patients newly started on
      warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in
      general medicine and surgery departments were included. The three endpoints were
      as follows: (i) percentage of international normalized ratios (INRs) achieving
      therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii)
      subtherapeutic INRs on discharge. RESULTS AND DISCUSSION: A total of 26 patients
      in the control period were compared with 144 patients who had received dosing
      consultations by a pharmacist during the initiation of warfarin. The provision of
      pharmacist consult resulted in 88% compared to 38% (P < 0.001) of INR values
      achieving therapeutic range within 5 days. There was a reduction in INR values of
      more than 4 during titration from 27% to 2% (P < 0.001), and subtherapeutic INR
      values on discharge without low molecular weight heparin from 15% to 0% (P <
      0.001). The mean time to therapeutic INR was reduced from 6.5 to 3.9 days (P <
      0.001) and mean length of stay after initiation of warfarin from 11 to 7.7 days
      (P = 0.004). WHAT IS NEW AND CONCLUSION: Inpatient anticoagulation care and
      outcomes were significantly improved by a pharmacist-managed anticoagulation
      service. The time to therapeutic INR was achieved appropriately and efficiently
      without compromising patient's safety.

PMID- 21070295
TI  - Assessment of the functionality of genome-wide canine SNP arrays and implications
      for canine disease association studies.
AB  - Domestic dogs share a wide range of important disease conditions with humans,
      including cancers, diabetes and epilepsy. Many of these conditions have similar
      or identical underlying pathologies to their human counterparts and thus dogs
      represent physiologically relevant natural models of human disorders. Comparative
      genomic approaches whereby disease genes can be identified in dog diseases and
      then mapped onto the human genome are now recognized as a valid method and are
      increasing in popularity. The majority of dog breeds have been created over the
      past few hundred years and, as a consequence, the dog genome is characterized by
      extensive linkage disequilibrium (LD), extending usually from hundreds of
      kilobases to several megabases within a breed, rather than tens of kilobases
      observed in the human genome. Genome-wide canine SNP arrays have been developed,
      and increasing success of using these arrays to map disease loci in dogs is
      emerging. No equivalent of the human HapMap currently exists for different canine
      breeds, and the LD structure for such breeds is far less understood than for
      humans. This study is a dedicated large-scale assessment of the functionalities
      (LD and SNP tagging performance) of canine genome-wide SNP arrays in multiple
      domestic dog breeds. We have used genotype data from 18 breeds as well as wolves
      and coyotes genotyped by the Illumina 22K canine SNP array and Affymetrix 50K
      canine SNP array. As expected, high tagging performance was observed with most of
      the breeds using both Illumina and Affymetrix arrays when multi-marker tagging
      was applied. In contrast, however, large differences in population structure, LD
      coverage and pairwise tagging performance were found between breeds, suggesting
      that study designs should be carefully assessed for individual breeds before
      undertaking genome-wide association studies (GWAS). 

PMID- 21070297
TI  - Variation of inflammatory parameters after sibutramine treatment compared to
      placebo in type 2 diabetic patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: The efficacy of sibutramine has been demonstrated in
      randomized trials in obese/overweight patients including those with type 2
      diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1-year
      treatment with sibutramine compared to placebo on body weight, glycaemic control,
      lipid profile, and inflammatory parameters in type 2 diabetic patients. METHODS:
      Two hundred and forty-six patients with uncontrolled T2DM [glycated haemoglobin
      (HbA(1c) ) > 8.0%] in therapy with different oral hypoglycaemic agents or insulin
      were randomized to take 10 mg of sibutramine or placebo for 12 months. We
      evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body
      weight, body mass index (BMI), HbA(1c) , fasting plasma glucose (FPG), post
      prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model
      assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low
      density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol
      (HDL-C), triglycerides (Tg), leptin, tumour necrosis factor-alpha (TNF-alpha),
      adiponectin (ADN), vaspin, high sensitivity C-reactive protein (Hs-CRP). RESULTS
      AND DISCUSSION: We observed a decrease of body weight after 9 and 12 months in
      the group treated with sibutramine, but not in the control group. Regarding
      glycaemic and lipid profile, although there are differences seen over time within
      each of the groups, we did not obtain any significant differences between the two
      groups. Both placebo and sibutramine gave a similar improvement of HOMA-IR,
      leptin, TNF-alpha, ADN, and Hs-CRP. No vaspin variations were observed in either
      group. WHAT IS NEW AND CONCLUSION: Sibutramine resulted in a decrease in body
      weight at 9 months and at 12 months that was not observed with placebo. Although
      there were differences seen over time within each of the groups, there were no
      significant differences between groups for any other parameter that we measured.

PMID- 21070298
TI  - The uncertainty of nanotoxicology: report of a Society for Risk Analysis
      Workshop.
AB  - A September 2008 workshop sponsored by the Society for Risk Analysis(() (1) ())
      on risk assessment methods for nanoscale materials explored "nanotoxicology" in
      risk assessment. A general conclusion of the workshop was that, while research
      indicates that some nanoscale materials are toxic, the information presented at
      the workshop does not indicate the need for a conceptually different approach for
      risk assessment on nanoscale materials, compared to other materials. However, the
      toxicology discussions did identify areas of uncertainty that present a challenge
      for the assessment of nanoscale materials. These areas include novel metrics,
      characterizing multivariate dynamic mixtures, identification of toxicologically
      relevant properties and "impurities" for nanoscale characteristics, and
      characterizing persistence, toxicokinetics, and weight of evidence in
      consideration of the dynamic nature of the mixtures. The discussion also
      considered "nanomaterial uncertainty factors" for health risk values like the
      Environmental Protection Agency's reference dose (RfD). Similar to the general
      opinions for risk assessment, participants expressed that completing a data set
      regarding toxicity, or extrapolation between species, sensitive individuals, or
      durations of exposure, were not qualitatively different considerations for
      nanoscale materials in comparison to all chemicals, and therefore, a
      "nanomaterial uncertainty factor" for all nanomaterials does not seem
      appropriate. However, the quantitative challenges may require new methods and
      approaches to integrate the information and the uncertainty.

PMID- 21070299
TI  - Responsible innovation: a pilot study with the U.K. Engineering and Physical
      Sciences Research Council.
AB  - Significant time lags between the development of novel innovations (e.g.,
      nanotechnologies), understanding of their wider impacts, and subsequent
      governance (e.g., regulation) have led to repeated calls for more anticipatory
      and adaptive approaches that promote the responsible emergence of new
      technologies in democratic societies. A key challenge is implementation in a
      pragmatic way. Results are presented of a study with the Engineering and Physical
      Sciences Research Council, the largest public funder of basic innovation research
      in the United Kingdom who, for the first time, asked applicants to submit a risk
      register identifying the wider potential impacts and associated risks
      (environment, health, societal, and ethical) of their proposed research. This
      focused on nanoscience for carbon capture and utilization. Risk registers were
      completed conservatively, with most identified impacts concerning researchers'
      health associated with nanoparticle synthesis, handling, and prototype device
      fabrication, i.e., risks that could be identified and managed with a reasonable
      level of certainty. Few wider environmental impacts and no future impacts on
      society were identified, reflecting the often uncertain and unpredictable nature
      of innovation. However, some applicants addressed this by including investigators
      with expertise beyond engineering and nanosciences supporting integrated
      activities that included life cycle and real-time technology assessment, which in
      some cases were also framed by stakeholder and/or public engagement. Proposals
      underpinned by a strong commitment to responsible science and innovation promoted
      continuous reflexivity, embedding a suite of multidisciplinary approaches around
      the innovation research core to support decisions modulating the trajectory of
      their innovation research in real-time.

PMID- 21070300
TI  - Moment independent importance measures: new results and analytical test cases.
AB  - Moment independent methods for the sensitivity analysis of model output are
      attracting growing attention among both academics and practitioners. However, the
      lack of benchmarks against which to compare numerical strategies forces one to
      rely on ad hoc experiments in estimating the sensitivity measures. This article
      introduces a methodology that allows one to obtain moment independent sensitivity
      measures analytically. We illustrate the procedure by implementing four test
      cases with different model structures and model input distributions. Numerical
      experiments are performed at increasing sample size to check convergence of the
      sensitivity estimates to the analytical values.

PMID- 21070301
TI  - Assessing the radiological impact of radiation exposure devices.
AB  - Radiation exposure devices (REDs) are radiological weapons obtained by concealing
      a strong gamma-emitting source in a place frequented by public to cause radiation
      injuries following the absorption of elevated radiation doses. The present work
      aims to assess the radiological impact of an RED by simulating its effects in
      both dynamical and static conditions of the covertly exposed population, with
      individual position and motion obtained through a Monte Carlo approach. The
      results indicate that in small enclosures the motion of people amplify the
      effects of radiation exposure with respect to the static case because it turns
      out in a larger number of individuals receiving doses above the threshold for the
      onset of deterministic effects. This behavior is mitigated in medium and large
      enclosures due to dose spreading over trajectories moving far away from the
      critical region close to the RED. The scaling laws obtained with a simple
      circular geometry were successfully applied to a more complex geometry like that
      of a stadium. The potentially large number of victims and the possibility to
      reiterate the attack raise the question of early detection. This can be achieved
      either by radiation survey or by indirectly inferring the presence of a strong
      radioactive source following the triage of patients with radiation sickness
      symptoms collected by the same hospital. In the former case careful design and
      operation of aerial or in situ monitoring is needed, while in the latter specific
      training should be given to healthcare personnel aimed to improve their
      discrimination and cooperation capabilities.

PMID- 21070302
TI  - Assessment of referrals to the hospital eye service by optometrists and GPs in
      Bradford and Airedale.
AB  - PURPOSE: To investigate the content of referrals to a hospital eye department and
      describe differences between referring clinician (optometrist or GP) and referral
      formats. METHODS: A random sample of 433 new referrals to Bradford Royal
      Infirmary hospital eye service (HES) during 2007 and 2008 were retrospectively
      analysed. RESULTS: Three hundred and eleven referrals (72%) were from optometric
      practice and 122 (28%) from general practice. Optometric referrals were mainly
      for cataract and posterior capsular opacification (27%), glaucoma or suspect
      glaucoma (20%) and diabetic retinopathy (10%). CONCLUSIONS: The proportion of
      referrals to the hospital eye service from optometrists appears to be increasing
      (1988: 39%, 1999: 48%, present study 72%). GPs mainly refer patients with
      anterior segment disorders, particularly lid lesions, based on direct observation
      and symptoms. Optometrists refer patients with a wide range of ocular diseases
      and include fundus observations and visual acuity measurements in their
      referrals. There is a need to inform optometrists of what content is required in
      a referral to the HES from GOS sight tests, at least for the common referral
      conditions such as age-related cataract and suspect open-angle glaucoma. Referral
      forms specifically designed for these commonly referred conditions are likely to
      improve referral quality.

PMID- 21070303
TI  - Cloning and tissue expression of the equine transferrin receptor.
AB  - BACKGROUND: Characterization of anemia in horses presents a challenge, as they do
      not release reticulocytes into peripheral blood. Transferrin receptor (TfR)
      expression is highest on erythroid cells in people and rats, and measurement of a
      soluble serum form (sTfR) is used to quantify erythropoiesis in these species. We
      hypothesized that equine TfR (eTfR) expression is similar in quantity and
      distribution to that in these other species and thus has potential for
      characterization of the regenerative response in anemic horses. OBJECTIVE: This
      study was conducted to clone and sequence the eTfR gene and measure expression
      levels using quantitative real-time PCR and immunohistochemical (IHC) staining.
      METHODS: Total RNA from equine bone marrow was used to produce cDNA. The eTfR
      gene was amplified using pooled gene-specific primers, and PCR products were
      sequenced. Rapid amplification of cDNA ends was used to obtain the first 22
      nucleotides of the coding sequence. Quantitative PCR was performed using eTfR
      gene-specific primers, and IHC staining was used to localize TfR protein
      expression. RESULTS: The deduced amino acid (aa) sequence (767 aa) of the eTfR
      was 75-83% identical with sequences of the receptor in several other mammals. As
      in people and rats, eTfR mRNA expression was highest in the bone marrow, and
      distribution in other tissues was also similar. CONCLUSION: The eTfR gene is
      similar to that of other mammals in structure and expression levels. We
      hypothesize that it is also similar in function and that, following development
      of an immunoassay, determining sTfR concentrations will be useful for identifying
      the regenerative response in anemic horses.

PMID- 21070304
TI  - What is your diagnosis? Increased total CO2 concentration and negative anion gap
      in a foal.

PMID- 21070305
TI  - What is your diagnosis? Choanal swab from a young Gyrfalcon.

PMID- 21070306
TI  - Choroid plexus carcinoma cells in the cerebrospinal fluid of a Staffordshire Bull
      Terrier.
AB  - An 11-year-old female intact Staffordshire Bull Terrier was referred to the
      Queen's Veterinary School Hospital at the University of Cambridge with sudden
      onset of episodic behavioral changes, a mammary mass, and papilledema in the
      right eye. On physical examination the dog appeared depressed and had a head tilt
      to the right with anisocoria. Using magnetic resonance imaging, a broad-based
      lesion that obliterated the fourth ventricle was detected in the right brainstem.
      There was no evidence of pulmonary metastasis. Cerebrospinal fluid (CSF) was then
      obtained; fluid analysis showed an increased cell count (165 cells/MUL, reference
      interval 0-7 cells/MUL) and total protein (0.30 g/L, reference value <0.25 g/L).
      Cytologic evaluation revealed a population of atypical epithelial cells arranged
      in cohesive rafts and characterized by moderate to occasionally marked
      anisocytosis and anisokaryosis. The appearance was highly suspicious of a
      malignant epithelial neoplasm. The dog was euthanized and on postmortem
      examination an asymmetrical nonencapsulated cerebellar mass was found within the
      choroid plexus of the fourth ventricle with local extension into the
      cerebellopontine angle. Histologic sections of the cerebellar mass contained
      arborizing papillary structures covered by a single layer of atypical epithelial
      cells that showed local infiltration into the adjacent neuropil. The diagnosis
      was choroid plexus carcinoma. The atypical epithelial cells were negative for
      pancytokeratin and strongly positive for vimentin. The finding of clusters of
      choroid plexus epithelial cells in the CSF demonstrates the value of utilizing a
      relatively noninvasive diagnostic technique for diagnosis of choroid plexus
      tumors.

PMID- 21070307
TI  - Subcutaneous embryonal rhabdomyosarcoma in a dog: cytologic, immunocytochemical,
      histologic, and ultrastructural features.
AB  - A subcutaneous mass on the left antebrachium of an 11-year-old intact female
      English Pointer dog was evaluated presurgically by cytologic examination and
      immunocytochemical staining. The sample consisted of discrete, variably sized,
      markedly pleomorphic neoplastic cells that expressed vimentin with diffuse
      cytoplasmic staining, desmin with focal paranuclear staining, and myoglobin with
      diffuse cytoplasmic staining, consistent with a diagnosis of rhabdomyosarcoma.
      Lymphocytic and histiocytic markers were negative. Aspirates of the enlarged
      ipsilateral prescapular lymph node were positive for metastatic disease. Surgical
      excision of the tumor and lymph node were followed by histologic and electron
      microscopic examination. Histomorphologic appearance of neoplastic cells from the
      mass and the lymph node paralleled cytologic findings; the histologic diagnosis
      was round cell variant of embryonal rhabdomyosarcoma. By ultrastructural
      evaluation, cells contained numerous mitochondria and masses of cytoplasmic
      tangled myofilaments, features typical of rhabdomyoblasts. The dog received
      doxorubicin (30 mg/m(2) ) every 3 weeks for 5 treatments. Local recurrence
      developed 6 months after resection but was not treated. Despite a guarded
      prognosis and untreated local recurrence, the dog was still alive 18 months after
      surgery. Cytologic evaluation and immunocytochemical staining were pivotal for
      the presurgical diagnosis of rhabdomyosarcoma.

PMID- 21070308
TI  - What is your diagnosis? Urine sediment from a southern California cat with weight
      loss.

PMID- 21070309
TI  - Methodological research and research about methods in caring sciences.

PMID- 21070310
TI  - Rodgers' evolutionary concept analysis--a valid method for developing knowledge
      in nursing science.
AB  - In nursing science, concept development is a necessary prerequisite for
      meaningful basic research. Rodgers' evolutionary concept analysis is a method for
      developing knowledge in nursing science. The purpose of this article is to
      present Rodgers' evolutionary concept analysis as a valid scientific method. A
      brief description of the evolutionary process, from data collection to data
      analysis, with the concepts' context, surrogate and related terms, antecedents,
      attributes, examples and consequences, is presented. The phases used in
      evolutionary concept analysis are illustrated with eight actual studies (1999
      2009) from nursing research. The strength of the method is that it is systematic,
      with a focus on clear-cut phases during the analysis process, and that it can
      contribute to clarifying, describing and explaining concepts central to nursing
      science by analysing how a chosen concept has been used both within the
      discipline itself and other health sciences. While an interdisciplinary
      perspective which stresses the similarities and dissimilarities of how a concept
      is used in various disciplines can increase knowledge of a concept, it is
      important to clarify the specific with the discipline. Nursing research should
      focus on the unambiguous use of concepts, for which Rodgers' method constitutes a
      possible method. The importance of using quality criteria to determine the
      inclusion of material should, however, be emphasised in the continued development
      of the method.

PMID- 21070311
TI  - Narrative hermeneutics: in search of narrative data.
AB  - As human beings, we live in a storied world. This worldview requires us to think
      about how to re-present it in research. My purpose with this article is to
      reflect upon narratives from an ontological and epistemological point of view,
      taking Ricoeur's writings on narrative identity as a starting point. From this
      perspective, narration is an aspect of self-interpretation and self
      understanding. Furthermore, self-understanding is not only achieved within our
      own narratives, but depends upon the regard, words and actions of others. This
      must be accounted for in our search for narrative data. Researchers would benefit
      from being alert to this and also aware of how narratives are co-authored in a
      dialogue with participants. Reflections on narration from this perspective could
      guide ethical considerations - and also methodological - as they could support
      questions that would create space for the narrative. Furthermore, the researcher
      must be aware that the quality and trustworthiness of narratives to a high degree
      depend on the researcher and not only on the participant.

PMID- 21070312
TI  - Psychometric evaluation of the Dutch Resilience Scale RS-nl on 3265 healthy
      participants: a confirmation of the association between age and resilience found
      with the Swedish version.
AB  - The aim of this study was to complete a thorough psychometric evaluation of the
      'RS-nl', a Dutch adaptation of the Wagnild and Young Resilience Scale. All of the
      25 items of the original RS were retained, but a 4-point rather than a 7-point
      response was used and one item was reworded by removal of the negation.
      Psychometric analyses on 3265 healthy participants revealed a significant
      positive association between age and the total resilience score, confirming the
      findings with the Swedish version by Lundman et al. To a lesser extent,
      associations between education and the subscale 'Personal Competence' and between
      gender and the subscale 'Acceptance of Self and Life' was found. There was,
      however, no strong evidence for a five factor structure reflecting the five
      characteristics described by Wagnild and Young, mainly because of high secondary
      loadings. Therefore, in accordance with the 25-item RS, a two factor model
      (creating the subscales 'Personal Competence' and 'Acceptance of Self and Life')
      was maintained. The RS-nl seems to be a valid and useful screening instrument to
      detect persons at risk, who could benefit from closer and prolonged psychological
      help.

PMID- 21070313
TI  - Levothyroxine replacement therapy and refractory hypotension out of transitional
      period in preterm infants.
AB  - BACKGROUND: Recent studies suggest that refractory hypotension from causes other
      than septicaemia or cardiac failure is common in extremely preterm infants even
      out of the transitional period. Marked response to low-dose cortisol suggests
      underlying adrenal insufficiency, although the exact mechanism remains unknown.
      METHODS: To investigate potential triggers for and related short-term outcomes of
      early-onset (<Day 7) and late-onset (>=Day 7) refractory hypotension, clinical
      data for 70 infants <30 weeks gestation were assessed. RESULTS: The incidence of
      early-onset refractory hypotension (n=7) was correlated with younger gestational
      ages <26 weeks (P < 0.05), whereas the incidence of late-onset refractory
      hypotension (n=14) was correlated with younger gestational ages and levothyroxine
      supplementation (P<0.05 and 0.01, respectively). The incidence of both early- and
      late-onset refractory hypotension was correlated with risks of short-term adverse
      outcomes such as prolonged mechanical ventilation and hospital stay. CONCLUSIONS:
      Levothyroxine supplementation was identified as an independent variable
      correlated with an increased incidence of refractory hypotension out of the
      transitional period; as seen in hypothyroidism with Addison's disease, the
      immature hypothalamic-pituitary-adrenal axis may not respond properly to the
      increased demand for cortisol, which may precipitate premature infants into
      refractory hypotension. Following the administration of levothyroxine, preterm
      infants may have to be carefully monitored for early signs of refractory
      hypotension.

PMID- 21070314
TI  - The size of adrenal incidentalomas correlates with insulin resistance. Is there a
      cause-effect relationship?
AB  - CONTEXT: Adrenal incidentalomas (AI) have often been associated with a high
      prevalence of insulin resistance (IR) and cardiovascular risk factors, although
      direct measurement of insulin sensitivity (IS) has never been carried out.
      OBJECTIVE: We aimed to investigate whether the morphological and hormonal
      features of AI correlate with the presence and severity of IR, using the
      hyperinsulinaemic euglycaemic clamp (HEC). DESIGN AND MEASUREMENTS: Forty
      patients with AI (22 women) with a mean age of 58.5+/-11.1 years underwent
      hormonal and morphological evaluation. Nineteen patients with AI without known
      history of diabetes mellitus (DM) or impaired glucose tolerance (IGT) and 17
      matched controls underwent oral glucose tolerance test (OGTT) and
      hyperinsulinaemic euglycaemic clamp (HEC). RESULTS: Diabetes mellitus was
      observed in 13 patients (33%), while three (8%) had IGT. Thirty-one of the AI
      were nonfunctioning (82.5%), whereas two (5%) secreted cortisol (Cushing's
      syndrome) and seven (12.5%) showed subclinical secretion of cortisol. The 19
      patients with nonfunctioning AI were more insulin resistant than controls
      (glucose up-take: 4.58+/-1.80 vs 5.85+/-2.48 mg/kg/min respectively; P=0.01); IS
      was inversely related to the mass size (r=-0.57; P=0.04), free urinary cortisol
      (r=-0.68; P=0.01), serum cortisol after 1-mg dexamethasone suppression (-0.65;
      P=0.02) and percentage of trunk fat mass (-0.77; P=0.02) and directly related to
      serum adreno cortico tropic hormone (ACTH) (r=0.62; P=0.03). After performing
      multivariate regression, the mass size was found to be the most powerful
      predictor of IR. CONCLUSION: Our study showed a high prevalence of insulin
      resistance in patients with nonfunctioning AI and suggests its possible
      involvement in AI growth.

PMID- 21070315
TI  - The role of heterozygous mutations of the autoimmune regulator gene (AIRE) in non
      APECED autoimmunity: a comment on recent findings.

PMID- 21070316
TI  - Psychological distress and social support are determinants of changing oral
      health status among an immigrant population from Ethiopia.
AB  - OBJECTIVES: To examine associations between psychosocial profile (psychological
      distress and social support) and changing oral health status (dental caries and
      periodontal disease), among a group of immigrants from Ethiopia to Israel.
      METHODS: Three hundred and forty immigrants, aged 18-75 years, with a mean age of
      38.4+/-13.5 years, comprised the study population and were followed over a 5-year
      period. Dental caries was recorded employing the DMFT index. Periodontal health
      status was recorded employing the Community Periodontal Index (CPI). Participants
      were interviewed using a structured written questionnaire which included two
      validated psychosocial scales, for psychological distress and social support.
      Bivariate and multivariate analyses were performed. RESULTS: Among subjects with
      psychological distress, the adjusted mean caries (DMFT) increment in 2004-2005,
      since baseline (1999-2000), was 3.52+/-0.19 when compared to 0.35+/-0.15 among
      subjects with no psychological distress (P<0.001). Correspondingly, the
      percentage of people with increased periodontal pockets was 40%, when compared to
      7%, respectively (P<0.001). In multiple linear regression analysis employing the
      DMFT as a continuous variable, and in multiple logistic regression analysis
      employing the DMFT as a dichotomous variable (% caries versus % caries-free), the
      four variables that reached statistical significance as predictors of caries
      status were previous caries experience, psychological distress, social support,
      and age. Gender, income, and education were not significantly related to current
      caries prevalence. In a multiple logistic regression analysis, the three
      variables that reached statistical significance as predictors of periodontal
      disease (shallow and deep pockets) were previous periodontal disease experience,
      psychological distress, and age. Social support, gender, income, and education
      were not significantly associated with periodontal disease prevalence.
      CONCLUSIONS: This study presents persuasive evidence that supports the role of
      psychological distress and social support as determinants of changing oral health
      levels, among a low socioeconomic, relatively homogenous immigrant minority
      population.

PMID- 21070317
TI  - Regression models for patient-reported measures having ordered categories
      recorded on multiple occasions.
AB  - OBJECTIVES: The article reviews proportional and partial proportional odds
      regression for ordered categorical outcomes, such as patient-reported measures,
      that are frequently used in clinical research in dentistry. METHODS: The
      proportional odds regression model for ordinal data is a generalization of
      ordinary logistic regression for dichotomous responses. When the proportional
      odds assumption holds for some but not all of the covariates, the lesser known
      partial proportional odds model is shown to provide a useful extension. RESULTS:
      The ordinal data models are illustrated for the analysis of repeated ordinal
      outcomes to determine whether the burden associated with sensory alteration
      following a bilateral sagittal split osteotomy procedure differed for those
      patients who were given opening exercises only following surgery and those who
      received sensory retraining exercises in conjunction with standard opening
      exercises. CONCLUSIONS: Proportional and partial proportional odds models are
      broadly applicable to the analysis of cross-sectional and longitudinal ordinal
      data in dental research.

PMID- 21070318
TI  - An appraisal of the quality of published qualitative dental research.
AB  - OBJECTIVES: To appraise the quality of published qualitative research in
      dentistry and identify aspects of quality, which require attention in future
      research. METHODS: Qualitative research studies on dental topics were appraised
      using the critical appraisal skills programme (CASP) appraisal framework for
      qualitative research. The percentage of CASP criteria fully met during the
      assessment was used as an indication of the quality of each paper. Individual
      criteria were not weighted. RESULTS: Forty-three qualitative studies were
      identified for appraisal of which 48% had a dental public health focus.
      Deficiencies in detail of reporting, research design, methodological rigour,
      presentation of findings, reflexivity, credibility of findings and relevance of
      study were identified. Problems with quality were apparent irrespective of
      journal impact factor, although papers from low impact factor journals exhibited
      the most deficiencies. Journals with the highest impact factors published the
      least qualitative research. CONCLUSIONS: The quality of much of the qualitative
      research published on dental topics is mediocre. Qualitative methods are
      underutilized in oral health research. If quality guidelines such as the CASP
      framework are used in the context of a thorough understanding of qualitative
      research design and data analysis, they can promote good practice and the
      systematic assessment of qualitative research.

PMID- 21070319
TI  - Trends in socioeconomic disparities in oral health in Brazil and Sweden.
AB  - OBJECTIVES: To describe the dynamics of trends in socioeconomic disparities in
      oral health in Brazil and Sweden among adults, to assess whether trends follow
      expected patterns according to the inverse equity hypothesis. METHODS: In Sweden,
      we obtained nationally representative data for the years 1968, 1974, 1981, 1991
      and 2000, and in Brazil, for 16 state capitals in 1986 and in 2002. Trends in the
      prevalence of 'edentulism' and of 'teeth in good conditions' were described in
      two groups aged 35-44 with lower and higher economic standards, respectively.
      RESULTS: There was an annual decline in disparities in 'edentulism' of 0.4
      percentage points (pp) (95% CI = 0.2-0.7) in Brazil and 0.7pp (95% CI = 0.5-0.9)
      in Sweden, as a result of improvements in both income groups. Concerning 'teeth
      in good conditions', in Brazil, there was improvement only in the higher income
      group and absolute disparities have increased (0.5pp annually), while in Sweden,
      there was a nonsignificant decrease (0.3pp annually) with improvements in both
      groups. Since 1991 in Sweden and in 2002 in Brazil, our measures of socioeconomic
      disparities in 'edentulism' were not statistically significant. Trends did not
      differ by sex or dental visit. CONCLUSIONS: Despite improvements in both income
      groups and a decrease in disparities in 'edentulism', the poorer group in Brazil
      has seen no improvement in 'teeth in good conditions' and disparities have
      increased. It appears that Brazil and Sweden reflect different stages of trend
      for 'teeth in good conditions' and the same stages for 'edentulism', represented
      by the inverse equity hypothesis.

PMID- 21070321
TI  - Inequalities in prosthetic rehabilitation among elderly people: the importance of
      context.
AB  - OBJECTIVE: It has been demonstrated that social, economic, and environmental
      factors may influence individuals' oral health conditions, particularly among
      vulnerable groups such as elderly people. The aim of this study was to
      investigate the association between contextual factors and the need for full
      dental prosthesis among elderly people. METHODS: This was a cross-sectional
      population-based epidemiological study of multilevel nature, with two levels of
      analysis: individual and contextual (municipal). Data at the individual level
      were obtained from oral clinical examinations (WHO criteria) in 5349 individuals
      aged 65-74. Data at the contextual level were obtained from the United Nations
      Development Program for the 250 Brazilian municipalities participating in the
      survey. The outcome was the need for a full dental prosthesis for at least one
      arch. Exposures at the contextual level included socioeconomic, demographic, and
      dental service data. Data analysis used multilevel logistic regression. RESULTS:
      After controlling for individual socioeconomic, demographic, and dental service
      variables, the chance of needing full prosthesis was higher in municipalities
      with lower educational levels than in better-off ones (OR 1.57; 95% CI: 1.09
      2.27) and lower in municipalities with fewer dentists (per capita) (OR 0.71; 95%
      CI: 0.52-0.97), compared to those with more dentists. CONCLUSION: This study can
      contribute to the identification of priority municipalities, helping healthcare
      authorities and communities to formulate equitable public oral healthcare
      policies that improve the quality of life for this population.

PMID- 21070320
TI  - An evaluation of serum albumin, root caries, and other covariates in Gullah
      African Americans with type-2 diabetes.
AB  - OBJECTIVES: Associations between dental conditions and overall health have been
      previously reported. Investigators have also shown significant inverse
      relationships between serum albumin (a general health status marker) and root
      caries. This relationship was explored among a study population of Gullah African
      Americans (who have a considerably lower level of non-African genetic admixture
      when compared to other African American populations) with type-2 diabetes (T2DM)
      and self-reported history of normal kidney function (N=280). METHODS: Root caries
      indices were defined as total decayed and/or filled root surfaces. The coronal
      caries index [total decayed, missing, and/or filled coronal surfaces (DMFS)],
      level of glycemic control, total number of teeth, and other covariates were also
      evaluated. Logistic regression models were used to evaluate the associations
      between these factors and hypoalbuminemia (serum albumin concentrations <4 g/dl).
      RESULTS: Serum albumin concentrations ranged 2.4-4.5 g/dl (mean=3.8, SD=0.3),
      with 70.4% exhibiting hypoalbuminemia. Root caries totals ranged 0-38 (mean=1.3,
      SD=4.5) surfaces decayed/filled, while total teeth ranged 1-28 (mean=19.4,
      SD=6.2). DMFS totals ranged 2-116 (mean=55.2, SD=28.0). We failed to detect
      significant associations for root caries; however, the final multivariable
      logistic regression models showed significant associations between
      hypoalbuminemia and total teeth [odds ratio (OR)=0.93, P=0.01], poor glycemic
      control (OR=2.49, P<0.01), elevated C-reactive protein (OR=1.57, P<0.01),
      glomerular filtration rates >=60 (OR=0.31, P=0.03), and age (OR=0.97, P=0.03).
      CONCLUSIONS: Previously reported inverse relationships between serum albumin and
      root caries were not evident in our study population. We propose that these null
      findings are because of the considerably lower level of root caries as well as
      other differing characteristics (including oral health status, the chronic
      presence of T2DM, and predominantly younger age) within our study population
      compared to these previously assessed groups.

PMID- 21070322
TI  - Associations between oral and ocular dryness, labial and whole salivary flow
      rates, systemic diseases and medications in a sample of older people.
AB  - OBJECTIVE: To investigate the associations between age, gender, systemic
      diseases, medications, labial and whole salivary flow rates and oral and ocular
      dryness in older people. METHODS: Symptoms of oral and ocular dryness, systemic
      diseases, medications (coded according to the Anatomical therapeutic chemical
      (ATC) classification system), tobacco and alcohol consumption were registered,
      and unstimulated labial (LS) and unstimulated (UWS) and chewing-stimulated (SWS)
      whole salivary flow rates were measured in 668 randomly selected community
      dwelling elderly aged 65-95. RESULTS: Presence of oral (12%) and ocular (11%)
      dryness was positively correlated. Oral dryness was associated with low UWS, SWS
      and LS, and ocular dryness with low UWS and SWS. Oral and ocular dryness was
      related to female gender, but not to age. Only four persons in the healthy and
      nonmedicated subgroups reported oral and ocular dryness. The numbers of diseases
      and medications were higher in the older age groups and associated with oral and
      ocular dryness, low UWS, SWS and LS. On average, women were slightly older,
      reported more oral and ocular dryness and had lower UWS, SWS, LS and higher
      numbers of diseases and medications. High prevalence and odds ratios for oral
      dryness were associated with metabolic, respiratory and neurological diseases and
      intake of thyroid hormones, respiratory agents (primarily glucocorticoids),
      psycholeptics and/or psychoanaleptics, antineoplastics, proton pump inhibitors,
      antidiabetics, loop diuretics, antispasmodics, quinine and bisphosphonates.
      Ocular dryness was especially associated with neurological diseases and intake of
      psycholeptics and/or psychoanaleptics. Intake of magnesium hydroxide,
      antithrombotics, cardiac agents, thiazides, beta-blockers, calcium channel
      blockers, ACE inhibitors/angiotensin II antagonists, statins, glucosamine,
      paracetamol/opioids, ophthalmologicals and certain combination therapies was
      related to oral and ocular dryness. CONCLUSIONS: In older people, oral and ocular
      dryness are associated with low salivary flow rates, specific as well as high
      number of diseases and medications, but neither with age and gender per se nor
      with tobacco and alcohol consumption. New detailed information concerning
      associations between medications and oral and ocular dryness has been obtained
      using the ATC classification system.

PMID- 21070323
TI  - Determinants of oral hygiene behavior: a study based on the theory of planned
      behavior.
AB  - OBJECTIVE: The aim of this study was to develop an index for oral hygiene
      behavior (OHB) and to examine potential predictors of this actual behavior based
      on the theory of planned behavior (TPB). Measures of oral health knowledge (OHK)
      and the expected effect of having healthy teeth on social relationships were
      included too. MATERIAL AND METHODS: Using an Internet questionnaire, 487
      participants were asked about actual OHB, attitudes (ATT), social norms (SN),
      perceived behavioral control (PBC), OHK, and expected social outcomes (ESO).
      Based on a Delphi method involving oral health professionals, a new index for OHB
      was developed, including tooth brushing, interdental cleaning, and tongue
      cleaning. RESULTS: Regression analysis revealed that the TPB variables (ATT, SN,
      and PBC) and OHK explained 32.3% of the variance in self-reported OHB.
      CONCLUSION: The present findings indicate that socio-psychological consequences
      play a role in oral health care.

PMID- 21070324
TI  - Periodontal disease and pre-eclampsia: a systematic review.
AB  - AIM: This review evaluates the possible relationship between periodontal disease
      and pre-eclampsia, a major pregnancy complication. A generalized inflammatory
      response plays an important role in the pathogenesis of pre-eclampsia. Because
      periodontal disease is a low-grade inflammatory state, periodontal disease might
      contribute to the pathogenesis of pre-eclampsia. MAIN FINDINGS AND CONCLUSION: A
      literature search of PubMed, EMBASE and CINAHL until August 2010 revealed 12
      eligible observational studies and three randomized-controlled trials (RCTs). It
      appeared difficult to compare these studies, due to variations in definitions of
      periodontal disease and pre-eclampsia, timing of periodontal examination and
      inadequate control for confounding factors. Eight observational studies reported
      a positive association, while four studies found no association. None of the RTCs
      reported reductions in pre-eclamptic rate after periodontal therapy during
      pregnancy. Therefore, it is questionable whether periodontal disease plays a
      causal role in the pathogenesis of pre-eclampsia. The observed association in
      eight observational studies might be the result of induction of periodontal
      disease due to the pre-eclamptic state or it may be an epiphenomenon of an
      exaggerated inflammatory response to pregnancy. Larger RCTs with pre-eclampsia as
      the primary outcome and pathophysiological studies are required to explore
      causality and to dissect biological mechanisms involved.

PMID- 21070325
TI  - Evidence-based periodontal plastic surgery: an assessment of quality of
      systematic reviews in the treatment of recession-type defects.
AB  - OBJECTIVE: To assess methods, quality and outcomes of systematic reviews (SRs)
      conducted to evaluate the effectiveness of root coverage (RC) procedures in the
      treatment of recession-type defects (RTD). METHODS: MEDLINE and EMBASE were
      searched up to and including April 2010 to identify SRs investigating the
      effectiveness/efficacy of surgical interventions for the treatment of patients
      with RTD. Searching was conducted independently by two reviewers, and data
      extraction was based on the methodological criteria applied and on the effects of
      interventions reported by each SR. The checklist proposed by Glenny and
      colleagues, the Overview Quality Assessment Questionnaire and the "Assessment of
      Multiple systematic Reviews", instrument were used to assess the quality of SRs.
      Additionally, the methodological criteria applied by included reviews were
      compared with those proposed by the Cochrane Collaboration. RESULTS: Search
      strategy identified 716 potentially eligible articles, of which 12 papers
      regarding 10 SRs were included in the study. Results from different SRs showed
      that subepithelial connective tissue grafts associated or not to coronally
      advanced flaps can be used to reduce recession depth and improve the width of
      keratinized tissue. All quality assessment tools showed that most of the SRs were
      of good methodological quality, but they also highlighted key points that could
      be improved in future reviews. Only two SRs followed in full the guidelines
      proposed by the Cochrane Collaboration. CONCLUSIONS: All SRs agree that RC may be
      anticipated by different surgical procedures. However, differences in the
      methodological quality between reviews were quite evident, and thus making a
      clear indication that there is a need of standardization of the methods that will
      be applied by future SRs. As a result, a standardized checklist for reporting SRs
      was proposed by the authors.

PMID- 21070326
TI  - Insulin sensitivity and periodontal infection in a non-diabetic, non-smoking
      adult population.
AB  - AIM: The aim of this study was to examine whether there is an association of
      insulin sensitivity with periodontal infection in a non-diabetic, non-smoking
      adult population. MATERIALS AND METHODS: A subpopulation of the Health 2000
      Survey (effective n=2050) consisted of dentate subjects without any indication of
      diabetes, aged between 30 and 64, and who had never smoked. The outcome variable
      was periodontal infection measured by means of the number of teeth with deepened
      periodontal pockets. Insulin sensitivity was measured using the homeostasis model
      assessment index for insulin resistance. Poisson regression models were used to
      estimate the relative risks and 95% confidence intervals. RESULTS: We found that
      insulin sensitivity was associated with periodontal infection in the age group 30
      49, but not in persons aged 50-64. Controlling for body weight made the
      association between insulin sensitivity and periodontal infection disappear.
      CONCLUSION: The lack of knowledge of the underlying causal model prevents making
      definite conclusions about the role of reduced insulin sensitivity in the
      pathogenesis of periodontal infection.

PMID- 21070327
TI  - Do malocclusion and Helkimo Index >= 5 correlate with body posture?
AB  - Whether there are correlations between the stomatognathic system and body posture
      remains controversial. Here, we have investigated whether malocclusal traits and
      having a Helkimo Index >= 5 show detectable correlations with body-posture
      alterations in children and young adults. A total of 1178 11- to 19-year-old
      subjects were divided into four groups: (i) controls; (ii) malocclusion; (iii)
      Helkimo Index >= 5 and (iv) malocclusion + Helkimo Index >= 5. Dental occlusion
      assessment included the following: overbite, overjet, posterior crossbite,
      scissorbite, mandibular crowding and dental class. Subsequently, body-posture
      assessments were performed through static analyses of body inclination and trunk
      asymmetry, and according to the dynamic Fukuda stepping test. Univariate and
      multivariate statistical analyses were performed. Although at the univariate
      level both the trunk asymmetry and Fukuda stepping test showed significant
      differences among the groups, the multivariate level revealed that age and gender
      were mostly responsible for this. The only significant correlation that was seen
      was for the malocclusion + Helkimo Index >= 5 group: these subjects had a
      positive (worse) trunk asymmetry and a negative (better) Fukuda stepping test
      performance. At the further multivariate analyses of each single malocclusal
      trait /Helkimo Index >= 5 (irrespective of the groups), only an increased
      overbite showed a statistically significant association with a slightly better
      Fukuda stepping test performance. Given the small number of significant
      associations seen and their limited entities, this study does not support the
      existence of clinically relevant correlations for malocclusal traits and Helkimo
      Index >= 5 with body posture in children and young adults.

PMID- 21070328
TI  - Survival rate and potential influential factors for two transitional implant
      systems in edentulous patients: a prospective clinical study.
AB  - The aim of this present study was to evaluate the success of immediately loaded
      transitional implants and to identify possible influential factors. A total of 64
      patients were recruited in a private specialist implant practice. Two different
      implant systems were evaluated (IPI, Nobel Biocare, Sweden; I-Plant, Unor,
      Switzerland). Primary stability, survival rate, gender, location, the type of
      prosthetic restoration and the tooth status of the opposite jaw were analysed
      using Kaplan-Meier or Pearson Chi-Square test. A total of 254 transitional
      implants were placed, thereof 216 were IPI implants and 38 I-Plant implants. The
      overall observation period ranged between 2 and 426 days. The results
      demonstrated a survival rate of 82.4% for the IPI system and 84.2% for the I
      Plant system. None of the transitional implants with a good primary stability
      were lost during the observation period. The primary stability showed significant
      influence on the implant survival. There was no significant difference in
      survival of the implants between the two implant systems. Neither the gender, the
      kind of superstructure, the location of the implant, the tooth status of the
      opposing jaw or the immediate prosthetic superstructure had an influence on the
      survival of the implants. Both implant systems proved to be sufficient
      alternatives for the support of provisional restorations.

PMID- 21070329
TI  - Pyoderma gangrenosum: an Indian perspective.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon, idiopathic, neutrophilic
      skin disease sometimes associated with systemic diseases. To our knowledge, there
      have been no case series of PG reported from India. AIM: To study the clinical
      features, associated systemic diseases and treatment methods in our case series.
      METHODS: In total, 18 cases of PG diagnosed at our institution in Mangalore were
      evaluated in a prospective study. RESULTS: Ulcerative PG was the most common
      variant, seen in all except one case. Paediatric patients constituted less than a
      quarter (27.77%) of the patients. Systemic diseases were associated with the
      disease in over half of the patients (55.55%). The pathergy test was positive in
      seven patients (38.88%), and all but one had associated systemic disease.
      Corticosteroids were mainly used for management. CONCLUSIONS: PG is a rare
      disease in India, but paediatric PG cases were relatively common. Ulcerative PG
      was the commonest type, and over half of the patients had associated systemic
      diseases. There were a significant number of patients with associated systemic
      disease who had a positive pathergy test.

PMID- 21070330
TI  - Unusual skin involvement in eosinophilic fasciitis.

PMID- 21070331
TI  - New dental enamel defects in coeliac disease.

PMID- 21070332
TI  - A novel mutation in LPAR6 causes autosomal recessive hypotrichosis of the scalp.
AB  - BACKGROUND: Autosomal recessive hypotrichosis simplex (ARHS) presents with
      progressive hair loss mainly affecting the scalp area. In a small number of
      families, the condition has been associated with mutations in three distinct
      genes: DSG4, LIPH and LPAR6. AIM: To identify the molecular basis of ARHS in a
      consanguineous family of Turkish extraction. METHODS: We used a combination of
      microsatellite marker screening and direct sequencing. RESULTS: We identified a
      novel missense mutation (c.C587T) in the human LPAR6 gene, resulting in the amino
      acid substitution p.P196L. The mutation affects a highly conserved amino acid
      residue, and is predicted to disrupt signalling through the P2Y5 receptor.
      CONCLUSIONS: This study provides further evidence supporting a role for the
      lysophosphatidyl signalling pathway in hair growth and differentiation. In
      addition, this paper reports, for the first time to our knowledge, the use of
      homozygosity mapping as a premutation screening tool in the diagnosis of a group
      of inherited hair disorders.

PMID- 21070334
TI  - Treatment of psoriasis in patients with hepatitis C virus infection.

PMID- 21070333
TI  - Effects of tacrolimus ointment on Toll-like receptors in atopic dermatitis.
AB  - BACKGROUND: Alterations of Toll-like receptors (TLRs) seem to play a role in
      susceptibility to atopic dermatitis (AD). AIM: To investigate the expression of
      TLRs in moderate to severe chronic AD in adults before and after a 3-week
      treatment with 0.1% tacrolimus ointment, compared with 0.1% topical
      hydrocortisone-17-butyrate. METHODS: In total, 21 adult patients with AD were
      enrolled: 11 were given tacrolimus ointment and 10 were given hydrocortisone
      butyrate; a further 6 healthy adults formed the control group. The clinical
      efficacy of the treatment was assessed using the SCORing Atopic Dermatis (SCORAD)
      index. Biopsies were taken from lesional skin before and after treatment, which
      were stained immunohistochemically with monoclonal antibodies to TLR-1, -2, -4
      and -9. RESULTS: Both 3-week topical treatments improved signs and symptoms in
      all 21 patients considered, with no significant difference between the two
      groups. In the skin of patients with AD, TLR-1 was overexpressed and TLR-2
      underexpressed compared with healthy controls, whereas no differences were found
      for TLR-4 and TLR-9. Staining for TLR-1 was decreased in both groups after
      treatment. AD specimens had higher levels of TLR-2 expression after either
      treatment compared with baseline, and levels were higher after tacrolimus
      treatment than after hydrocortisone butyrate. Neither tacrolimus nor
      hydrocortisone butyrate affected expression of TLR-4 or TLR-9. CONCLUSION: Short
      term therapy with tacrolimus ointment reduced expression of TLR-1, which may
      inhibit the antimicrobial potential of TLR-2, and also reversed the impairment of
      TLR-2 in AD lesions. Expression of TLR-4 and TLR-9 was not affected by
      tacrolimus.

PMID- 21070335
TI  - An open-label study assessing the safety and efficacy of alitretinoin in patients
      with severe chronic hand eczema unresponsive to topical corticosteroids.
AB  - BACKGROUND: Blinded, controlled studies have found that oral alitretinoin is well
      tolerated and effective in the treatment of severe chronic hand eczema (CHE).
      AIM: To assess the safety and efficacy of oral alitretinoin in patients with
      severe CHE in an open-label study using flexible dosing and a new measurement of
      patient-relevant benefits. METHODS: In total, 249 patients aged 18-75 years with
      severe CHE unresponsive to treatment with topical corticosteroids received
      alitretinoin 30 mg once daily for up to 24 weeks. Safety assessments included
      adverse events (AEs) and laboratory tests. Efficacy assessments included
      Physician's Global Assessment (PGA), the Modified Total Lesion Symptom Score,
      Patient's Global Assessment and extent of disease, as well as intensity of pain
      and pruritus as determined by visual analogue scale (VAS) and a categorical scale
      for pruritus. RESULTS: Alitretinoin was well tolerated when given for up to 24
      weeks. Dose reduction occurred in 16.5% of patients. Dose interruption was
      required for 15.7% of patients, most commonly for headache. AEs and laboratory
      changes comprised effects typical of the retinoid class. A PGA response of
      'clear' or 'almost clear' hands was reported for 46.6% of patients, similar to
      the response rate seen in blinded trials. Results of VAS and categorical
      assessments of pruritus provided supporting evidence of efficacy, and treatment
      was assessed as providing meaningful benefits to patients. CONCLUSIONS: Oral
      alitretinoin 30 mg was well tolerated and effective, and provided distinct
      therapeutic benefits in severe CHE, as assessed by patients.

PMID- 21070336
TI  - Rhizomucor variabilis infection in human cutaneous mucormycosis.

PMID- 21070337
TI  - The Woronoff ring and fumaric acid ester flush.

PMID- 21070338
TI  - Community photo-triage for skin cancer referrals: an aid to service delivery.
AB  - BACKGROUND: We wished to investigate the potential for extending the capacity of
      the specialist service by using community-based photo-triage for suspected skin
      cancers. AIMS: To compare the outcomes and costs of conventional and photo-triage
      referral pathways. METHODS: This was an observational study of conventional and
      photo-triage referrals. Patients referred for initial photo-triage were invited
      to visit a medical photographer located in community health centres, who would
      take high-quality close-up and dermatoscopic images of the patients' lesions. A
      dermatologist then reviewed the images, and triaged patients to specific
      treatment clinics. All patients referred by conventional letter were offered
      initial appointments at the consultant-delivered skin cancer clinic. The
      difference in costs was assessed by modelling health service use under both
      pathways. RESULTS: Photo-triage permitted 91% of patients (263/289) to achieve
      definitive care at first visit to the specialist team, compared with only 63%
      (117/186) via the conventional referral pathway. The mean waiting time to
      definitive treatment for patients with skin cancer was slightly reduced with
      photo-triage. Photo-triage permitted direct booking for 45% of patients to attend
      a nurse-delivered clinic, 22% to attend directly for surgery, 2% to attend a
      community general practice clinic and 2% to be referred on electronically to
      another specialty. This reduced by 72% the number of patients requiring
      attendance to the consultant clinic, freeing up capacity. Despite the cost of
      providing medical photography, there was a small cost saving of around L 1.70 per
      patient using photo-triage. CONCLUSIONS: Community photo-triage improved referral
      management of patients with suspected skin cancer, improving the delivery of
      definitive care at first visit and achieved an increased service capacity. Cost
      comparison found that the photo-triage model described was marginally cheaper
      than conventional care, and reduced hospital visits. An integrated primary
      secondary care referral pathway that includes photo-triage facilitates a more
      efficient specialist service while ensuring that all suspicious lesions are
      viewed by an experienced dermatologist.

PMID- 21070339
TI  - Value of the Tzanck smear test and dermatoscopy in the diagnosis of clear cell
      acanthoma.

PMID- 21070341
TI  - Collaborative research in medical education: a discussion of theory and practice.
AB  - CONTEXT: Medical education researchers are inherently collaborators. This paper
      presents a discussion of theoretical frameworks, issues and challenges around
      collaborative research to prepare medical education researchers to enter into
      successful collaborations. It gives emphasis to the conceptual issues associated
      with collaborative research and applies these to medical education research.
      Although not a systematic literature review, the paper provides a rich discussion
      of issues which medical education researchers might consider when undertaking
      collaborative studies. METHODS: Building on the work of others, we have
      classified collaborative research in three dimensions according to: the number of
      administrative units represented; the number of academic fields present, and the
      manner in which knowledge is created. Although some literature on collaboration
      focuses on the more traditional positivist perspective and emphasises outcomes,
      other literature comes from the constructivist framework, in which research is
      not driven by hypotheses and the approaches emphasised, but by the interaction
      between investigator and subject. DISCUSSION: Collaborations are more effective
      when participants overtly clarify their motivations, values, definitions of
      appropriate data and accepted methodologies. These should be agreed upon prior to
      commencing a study. The way we currently educate researchers should be
      restructured if we want them to be able to undertake interdisciplinary research.
      Despite calls for researchers to be educated differently, most training
      programmes for developing researchers have demonstrated a limited, if not
      contrary, response to these calls. CONCLUSIONS: Collaborative research in medical
      education should be driven by the problem being investigated, by the new
      knowledge gained and by the interpersonal interactions that may be achieved.
      Success rests on recognising that many of the research problems we, as medical
      educators, address are fundamentally interdisciplinary in nature. This represents
      a transition to bridge the dichotomy often presented in medical education between
      theory building and addressing practical needs.

PMID- 21070340
TI  - Characteristics of Staphylococcus aureus colonization in patients with atopic
      dermatitis in Sri Lanka.
AB  - BACKGROUND: Colonization of the skin of patients with atopic dermatitis (AD) by
      Staphylococcus aureus (SA) is associated with more severe disease. AIM: To
      determine the association of SA colonization patterns and densities in lesional
      and nonlesional skin in patients with varying severities of AD, and to determine
      the antibiotic sensitivity patterns of SA isolates from Sri Lanka. METHODS: Skin
      and nasal swabs collected from 100 patients with AD and 120 controls were used to
      investigate the presence of SA. Severity of AD was graded using the Nottingham
      Eczema Severity Score. Colony counts were obtained for skin samples, and
      antibiotic sensitivity testing was performed in cases positive for SA. RESULTS:
      Skin colonization was seen in 57 patients (57%) but in only 10 controls (8%).
      Lesional skin of most patients (52/57; 91%) had SA densities of > 300 colony
      forming units/cm(2) . Colonization rates with SA significantly increased with
      increasing age (Spearman correlation coefficient R = 0.9, P < 0.05) and
      increasing duration of lesions in patients with AD (Spearman R = 0.87, P < 0.05).
      Isolates from eight patients (13.5%) were found to be methicillin-resistant S.
      aureus (MRSA). Only 6 isolates (10%) were susceptible to penicillin and 22 (37%)
      to erythromycin, while 28 (47%) isolates had erythromycin-induced resistance to
      clindamycin. CONCLUSIONS: SA colonization rates were significantly associated
      with increasing age and severity of AD, and particularly with duration of
      lesions. Patients with severe disease were also more likely to be colonized with
      SA strains resistant to conventional antibiotics.

PMID- 21070342
TI  - Bias against foreign-born or foreign-trained doctors: experimental evidence.
AB  - OBJECTIVES: Bias against foreign-born or -trained medical students and doctors is
      not well understood, despite its documented impact on recruitment, integration
      and retention. This research experimentally examines the interaction of location
      of medical education and nationality in evaluations of doctors' competence and
      trustworthiness. METHODS: A convenience sample of prospective patients evaluated
      fictitious candidates for a position as a doctor in community practice at a new
      local health clinic. All applicants were described as having the same personality
      profile, legal qualifications to practise, a multi-degree education and relevant
      work experience. The location of medical education (the candidate's home country
      or the UK) and national background (Australia or Pakistan) of the applicants were
      independently experimentally manipulated. RESULTS: Consistent with previous
      research on skills discounting and bias, foreign-born candidates were evaluated
      less favourably than native-born candidates, despite their comparable education
      level, work experience and personality. However, overseas medical education
      obtained in the First World both boosted evaluations (of competence and
      trustworthiness) and attenuated bias based on nationality. CONCLUSIONS: The
      present findings demonstrate the selective discounting of foreign-born doctors'
      credentials. The data show an interaction of location of medical education and
      birth nationality in bias against foreign doctors. On an applied level, the data
      document that the benefits of medical education obtained in the First World can
      extend beyond its direct outcomes (high-quality training and institutional
      recognition) to the indirect benefit of the attenuation of patient bias based on
      nationality.

PMID- 21070343
TI  - Effects of comprehensive educational reforms on academic success in a diverse
      student body.
AB  - CONTEXT: Calls for medical curriculum reform and increased student diversity in
      the USA have seen mixed success: performance outcomes following curriculum
      revisions have been inconsistent and national matriculation of under-represented
      minority (URM) students has not met aspirations. Published innovations in
      curricula, academic support and pipeline programmes usually describe isolated
      interventions that fail to affect curriculum-level outcomes. METHODS: United
      States Medical Licensing Examination (USMLE) Step 1 performance and graduation
      rates were analysed for three classes of medical students before (matriculated
      1995-1997, n=517) and after (matriculated 2003-2005, n=597) implementing broad
      based reforms in our education system. The changes in pipeline recruitment and
      preparation programmes, instructional methods, assessment systems, academic
      support and board preparation were based on sound educational principles and best
      practices. RESULTS: Post-reform classes were diverse with respect to ethnicity
      (25.8% URM students), gender (51.8% female), and Medical College Admissions Test
      (MCAT) score (range 20-40; 24.1% scored <= 25). Mean+/-standard deviation MCAT
      scores were minimally changed (from 27.2+/-4.7 to 27.8+/-3.6). The Step 1 failure
      rate decreased by 69.3% and mean score increased by 14.0 points (effect size:
      d=0.67) overall. Improvements were greater among women (failure rate decreased by
      78.9%, mean score increased by 15.6 points; d=0.76) and URM students (failure
      rate decreased by 76.5%, mean score increased by 14.6 points; d=0.74), especially
      African-American students (failure rate decreased by 93.6%, mean score increased
      by 20.8 points; d=1.12). Step 1 scores increased across the entire MCAT range.
      Four- and 5-year graduation rates increased by 7.1% and 5.8%, respectively.
      CONCLUSIONS: The effect sizes in these performance improvements surpassed those
      previously reported for isolated interventions in curriculum and student support.
      This success is likely to have resulted from the broad-based, mutually
      reinforcing nature of reforms in multiple components of the education system. The
      results suggest that a narrow reductionist view of educational programme reform
      is less likely to result in improved educational outcomes than a system
      perspective that addresses the coordinated functioning of multiple aspects of the
      academic enterprise.

PMID- 21070344
TI  - Adaptive feedback and student behaviour in computer-assisted instruction.
AB  - OBJECTIVES: Two packages of adaptive computer-assisted instruction (CAIs), both
      offering questions and subsequent feedback, were compared in terms of amount of
      feedback offered, learning efficiency and appreciation. Feedback was either
      barely more than knowledge of result ('minimal') or consisted of a complete
      additional learning path ('elaborate'). The CAIs differed in the way the type of
      feedback given was triggered. METHODS: A total of 97 Bachelor of Science students
      were stratified based on a pre-test before the experiment and were allocated
      randomly to two groups to receive either a 'programme-assessed' or a 'student
      assessed' treatment. In the former, the feedback provided by the CAI (either
      elaborate or minimal) was completely determined by the objective correctness of
      the student's response. In the student-assessed treatment, elaborate feedback was
      provided only to students who stated explicitly that they did not know the
      answer. Afterwards, students completed a post-test and an appreciation
      questionnaire. RESULTS: Both CAIs resulted in a significant learning effect, but
      overall the effect was significantly higher in the programme-assessed treatment.
      Students using the student-assessed CAI hardly ever used the 'I don't know'
      option and therefore received mostly minimal feedback. There was no difference in
      students' appreciation between treatments. An interaction between the learner's
      prior knowledge and treatment was found: for learners with a high level of prior
      knowledge the programme-assessed treatment resulted in significantly higher
      learning effectiveness compared with the student-assessed treatment, whereas for
      learners with a low level of prior knowledge there was no significant difference.
      CONCLUSIONS: Our results demonstrate that learners achieved a significantly
      higher learning effectiveness in the programme-assessed treatment in which the
      received feedback was fully controlled by the correctness of the answer, compared
      with the student-assessed treatment. In the latter, students hardly ever admitted
      to not knowing the answer. Therefore, student-initiated use of the tool in a
      student-assessed CAI requires to be improved.

PMID- 21070345
TI  - Experiences of alcohol-related harassment among medical students.
AB  - OBJECTIVES: Although fatal accidents caused by alcohol-related harassment occur
      frequently among college students, this issue has not been adequately examined.
      This study set out to investigate the prevalence of alcohol-related harassment
      among medical students in Japan. METHODS: A multi-institutional, cross-sectional
      survey was carried out across seven medical schools in Japan. A self-report
      anonymous questionnaire was distributed to 1152 medical students; 951 respondents
      (82.6%) satisfactorily completed it. From the responses, we determined the
      reported prevalences of the following types of alcohol-related harassment among
      medical students by senior medical students or doctors: (i) being coerced into
      drinking alcohol; (ii) being compelled to drink an alcoholic beverage all at once
      (the ikki drinking game); (iii) being deliberately forced to drink until
      unconscious, and (iv) being subjected to verbal abuse, physical abuse or sexual
      harassment in relation to alcohol. The prevalence of becoming a harasser among
      medical students was also measured. Multivariate regressions were used to assess
      the associations between experiences of alcohol-related harassment and student
      characteristics. RESULTS: A total of 821 respondents (86.3%) had experienced
      alcohol-related harassment and 686 (72.1%) had harassed others. Experiences of
      the ikki drinking game were frequently reported by both victims (n=686, 72.1% of
      all respondents) and harassers (n=595, 62.6% of all respondents). In multivariate
      regression, having an experience of alcohol-related harassment correlated with
      both being harassed (odds ratio [OR] 14.22, 95% confidence interval [CI] 8.73
      23.98) and being a harasser (OR 13.19, 95% CI 8.05-22.34). The presence of senior
      members of medical college clubs who were regular drinkers also correlated with
      both being harassed (OR 2.96, 95% CI 1.88-4.67) and being a harasser (OR 2.97,
      95% CI 2.06-4.27). CONCLUSIONS: Alcohol-related harassment among medical students
      is common and tends to occur at drinking parties with senior college club
      members. Hence, one of the most important strategies for preventing alcohol
      related harassment may be to disrupt this vicious cycle.

PMID- 21070346
TI  - Evaluation of Vickers hardness of different types of acrylic denture base resins
      with and without glass fibre reinforcement.
AB  - OBJECTIVE: To evaluate the Vickers hardness of different acrylic resins for
      denture bases with and without the addition of glass fibres. BACKGROUND: It has
      been suggested that different polymerisation methods, as well as the addition of
      glass fibre (FV) might improve the hardness of acrylic. MATERIALS AND METHODS:
      Five types of acrylic resin were tested: Vipi Wave (VW), microwave
      polymerisation; Vipi Flash (VF), auto-polymerisation; Lucitone (LT), QC20 (QC)
      and Vipi Cril (VC), conventional heat-polymerisation, all with or without glass
      fibre reinforcement (GFR) and distributed into 10 groups (n = 12). Specimens were
      then submitted to Vickers hardness testing with a 25-g load for 30 s. All data
      were submitted to anova and Tukey's HSD test. RESULTS: A significant statistical
      difference was observed with regard to the polymerisation method and the GFR (p <
      0.05). Without the GFR, the acrylic resin VC presented the highest hardness
      values, and VF and LT presented the lowest. In the presence of GFR, VC resin
      still presented the highest Vickers hardness values, and VF and QC presented the
      lowest. CONCLUSIONS: The acrylic resin VC and VW presented higher hardness values
      than VF and QC resins. Moreover, GFR increased the Vickers hardness of resins VW,
      VC and LT.

PMID- 21070347
TI  - Children with atopic dermatitis appear less likely to be infected with community
      acquired methicillin-resistant Staphylococcus aureus: the San Diego experience.
AB  - Given the increasing rate of community-acquired methicillin resistant
      Staphylococcus aureus skin infections in the population, such infections might be
      concurrently increasing in patients with atopic dermatitis. This study assessed
      current and prior rates of community-acquired methicillin resistant
      Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus skin and
      soft tissue infections in children with atopic dermatitis compared to the general
      pediatric population. Other antibiotic sensitivity and resistance patterns,
      including clindamycin-inducible resistance, were also identified. Retrospective
      study of all skin and soft tissue isolates were positive for Staphylococcus
      aureus during two distinct 1-year periods, obtained by the outpatient services
      and the emergency department at Rady Children's Hospital, the major regional
      pediatric health center in San Diego, California. Of the Staphylococcus aureus
      isolates obtained from January to December 2000, none from atopic dermatitis
      patients were methicillin resistant Staphylococcus aureus, while 4.2% of those
      obtained from the general outpatient pediatric population showed methicillin
      resistance. In the period from June 2007 to May 2008, 11 of 78 isolates (14.1%)
      from children with atopic dermatitis were methicillin resistant Staphylococcus
      aureus. This was significantly lower than the rate of increase noted in the
      general pediatric population (658 of 1482, or 44.4%, in 2007/2008, p < 0.05).
      Clindamycin-inducible resistance was noted in 1.9% of the isolates in the general
      population; all six tested isolates from atopic patients lacked clindamycin
      inducible resistance. In this study, children with atopic dermatitis had a much
      lower rate of community-acquired methicillin resistant Staphylococcus aureus
      infection compared to the general outpatient pediatric population. Clindamycin
      inducible resistance was very low in both groups.

PMID- 21070348
TI  - Omphalomesenteric duct remnants: umbilical versus umbilical cord lesions.
AB  - The omphalomesenteric duct is an embryologic connection between the digestive
      tract and yolk sac, which typically involutes by the time of birth. Failure of
      the obliteration process can result in omphalomesenteric duct remnants. We
      present two cases of children with such remnants, one with an umbilical polyp
      requiring traditional excisional therapy and one more unusual case of an
      umbilical cord cyst resolving spontaneously without intervention. The
      differential diagnosis, which includes urachal remnants and umbilical pyogenic
      granulomas, is discussed, along with management and special considerations that
      practioners should be aware of when treating pediatric umbilical and umbilical
      cord lesions.

PMID- 21070350
TI  - Gender differences in treatment of cardiovascular disease: a task force on gender
      of the ESC proposal on gender specific studies in cardiovascular pharmacology.

PMID- 21070351
TI  - Combined off-pump transapical transcatheter aortic valve implantation and
      minimally invasive direct coronary artery bypass.
AB  - Transcatheter aortic valve implantation has been shown to be an effective
      treatment for severe aortic stenosis in high-risk surgical patients. Many of
      these patients have significant coexisting coronary artery disease. We report the
      first case of combined off-pump transapical aortic valve implantation and
      minimally invasive direct coronary artery bypass via a left mini-thoracotomy in
      an 82-year-old man with significant comorbidities. This combined procedure is
      technically feasible and can be performed safely in selected patients with aortic
      stenosis and left anterior descending artery lesion that is not suitable for
      percutaneous intervention.

PMID- 21070352
TI  - Abscess transformation of intracardiac hematoma and ventricular rupture after
      double-patch repair of postinfarction ventricular septal defect.
AB  - A 69-year-old male patient underwent double-patch repair for a postinfarction
      ventricular septal defect (VSD). He returned five months later with an abscess in
      the area of a postoperative hematoma between the patch and the left ventricle.
      The abscess was drained and the ventricles were successfully reconstructed.
      Intracardiac hematoma after double-patch repair of postinfarction VSD should be
      closely followed up and, if there are any infection signs, aggressive surgical
      management should be performed.

PMID- 21070353
TI  - Successful repair of a traumatic ventricular septal defect using an amplatzer
      occluder guided by three-dimensional transesophageal echocardiography.
AB  - Transesophageal echocardiogram (TEE) guided perventricular cardiac intervention
      has gained popularity in recent years. We present a special case of
      perventricular closure conducted for a traumatic apical muscular ventricular
      septal defect (mVSD) under the guidance of three-dimensional (3D) TEE with an
      Amplatzer mVSD occluder and further discuss the important role of 3D TEE in
      perventricular cardiac intervention.

PMID- 21070355
TI  - Public reporting of cardiac surgery outcomes--what do we know, what can we
      expect?

PMID- 21070354
TI  - Left main coronary artery fistula to the right atrium and superior vena cava:
      case report and review of the literature.
AB  - A unique arteriovenous fistula, originating from the left main coronary artery
      and branching to drain into the right atrium and superior vena cava is presented
      with review of the literature.

PMID- 21070356
TI  - Repair of truncus arteriosus: choice of right ventricle outflow reconstruction.
AB  - OBJECTIVE: To find a better method of right ventricular-pulmonary artery (RV-PA)
      reconstruction in repairing truncus arteriosus (TA). BASIC STUDIES DESIGN:
      Retrospective clinical study, contrast study. CLINICAL SETTING: Shanghai
      Children's Medical Center. PARTICIPANTS: 23 patients with truncus arteriosus.
      INTERVENTION: To decrease the man-made interference, all of the exams during the
      follow-up period were carried out at our center. MAIN OUTCOME MEASUREMENTS:
      Hospital death, survival rate, the later outcomes during follow-up including the
      growth of pulmonary artery, the later heart function, and reintervention.
      RESULTS: There were two early hospital deaths, with no deaths during follow-up.
      The overall survival rate was 91.30%. One patient underwent reintervention for
      RVOTO. In Group 1, the difference between the diameters of RV-PA anastomosis was
      statistically significant. The early diameter was 1.01 +/- 0.26 cm, the later was
      1.32 +/- 0.45 cm, p = 0.019. The velocity of flow at the position of anastomosis
      and the orifice of RPA/LPA was acceptable. There was a significant difference
      between the growth ratio of the RV-PA anastomosis of two groups, with a p value
      of 0.048. The later ejection fraction was higher than the early one in both
      groups. There was no reintervention for truncal valve regurgitation. CONCLUSIONS:
      The postoperative survival and follow-up results were satisfactory. A direct
      anastomosis of RV-PA continuity has the potential for RVOT growth and is
      associated with a low ratio of pulmonary artery and bifurcation obstruction. The
      myocardial function improved during follow-up period. IAA was a major risk factor
      associated with hospital death.

PMID- 21070358
TI  - The Neopuff's PEEP valve is flow sensitive.
AB  - AIM: The current recommendation in setting up the Neopuff is to use a gas flow of
      5-15 L/min. We investigated if the sensitivity of the positive end expiratory
      pressure (PEEP) valve varies at different flow rates within this range. METHODS:
      Five Neopuffs were set up to provide a PEEP of 5 cm H(2) O. The number of
      clockwise revolutions to complete occlusion of the PEEP valve and the mean and
      range of pressures at each quarter clockwise revolution were recorded at gas flow
      rates between 5 and 15 L/min. RESULTS:   At 5, 10 and 15 L/min, 0.5, 1.7 and 3.4
      full clockwise rotations were required to completely occlude the PEEP valve, and
      pressures rose from 5 to 11.4, 18.4 and 21.5 cm H(2) O, respectively. At a flow
      rate of 5 L/min, half a rotation of the PEEP dial resulted in a rise in PEEP from
      5 to 11.4cm H(2) O. At 10 L/min, half a rotation resulted in a rise from 5 to
      7.7cm H(2) O, and at 15 L/min PEEP rose from 5 to 6.8cm H(2) O. CONCLUSION: Users
      of the Neopuff should be aware that the PEEP valve is more sensitive at lower
      flow rates and that half a rotation of the dial at 5 L/min gas flow can more than
      double the PEEP.

PMID- 21070357
TI  - Life and death decisions for incompetent patients: determining best interests-
      the Irish perspective.
AB  - AIMS: To determine whether healthcare providers apply the best interest principle
      equally to different resuscitation decisions. METHODS: An anonymous questionnaire
      was distributed to consultants, trainees in neonatology, paediatrics, obstetrics
      and 4th medical students. It examined resuscitation scenarios of critically ill
      patients all needing immediate resuscitation. Outcomes were described including
      survival and potential long-term sequelae. Respondents were asked whether they
      would intubate, whether resuscitation was in the patients best interest, would
      they accept surrogate refusal to initiate resuscitation and in what order they
      would resuscitate. RESULTS: The response rate was 74%. The majority would wish
      resuscitation for all except the 80-year-old. It was in the best interest of the
      2-month-old and the 7-year-old to be resuscitated compared to the remaining
      scenarios (p value <0.05 for each comparison). Approximately one quarter who
      believed it was in a patient best interests to be resuscitated would nonetheless
      accept the family refusing resuscitation. Medical students were statistically
      more likely to advocate resuscitation in each category. CONCLUSION: These results
      suggest resuscitation is not solely related to survival or long-term outcome and
      the best interest principle is applied differently, more so at the beginning of
      life.

PMID- 21070359
TI  - Thin newborns are more insulin resistant at 10 years of age.
AB  - AIMS: To investigate the relation between ponderal index or birth weight and
      insulin resistance in late childhood. METHODS: An observational study of 92-term
      appropriate-for-gestational age infants was carried out. Weight and length were
      measured at birth and at 9 months and duration of breast feeding was noted at 9
      months. Follow-up examinations at 10 years of age included measurement of weight,
      height, pubertal status, fasting insulin and glucose concentrations. RESULTS:
      Ponderal index at birth was negatively (B+/-SE=-0.05+/-0.02; p=0.025) and current
      BMI was positively (B+/-SE=0.14+/-0.02; p<0.001) associated with insulin
      resistance measured as homeostasis model assessment (HOMA) at 10 years of age
      adjusted for gender and pubertal stage. Current BMI and ponderal index at birth
      were still significant after adjusting for weight at 9 months. Birth weight and
      weight at 9 months was not correlated with HOMA (p=0.58) adjusted for current
      BMI, gender and pubertal stage. HOMA was higher in the tertile with the lowest
      ponderal index than in the two remaining tertiles (p=0.024). CONCLUSION: Relative
      thinness at birth, but neither birth weight nor weight gain from 0-9 months, was
      associated with higher insulin resistance at 10 years of age in this cohort with
      a low prevalence of overweight at 10 years of age and normal birth weight.

PMID- 21070360
TI  - Future role of gastroenterologists in digestive oncology in the Asia Pacific
      region: Panir Chelvam Memorial Lecture, Asian Pacific Digestive Week 2010.
AB  - There is an increasing burden in digestive cancer in the coming years. With the
      advancement of endoscopic therapy, new molecular target therapy and minimally
      invasive ablation therapy, the treatment of digestive cancer will become more
      complicated. In Asia where gastric cancer and hepatocellular carcinoma are still
      prevalent and colorectal cancer is rapidly on the rise, the need in digestive
      oncology will be even higher. A new subspecialty of digestive oncology will be
      needed from the patient's perspective, from the healthcare authority's viewpoint
      and for the future development of gastroenterology.

PMID- 21070361
TI  - Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?
AB  - Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are
      attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV)
      infection. Thus, effective prevention of HBV and HCV infection and progression
      from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might
      prevent as many as 450,000 deaths from HCC each year. The most effective approach
      to preventing HCC is to prevent HBV and HCV infection through vaccination. Indeed
      HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a
      vaccine for HCV is not available and for persons who are chronically infected
      with HBV or HCV, antiviral therapy is the only option for preventing HCC. Direct
      evidence supporting a benefit of antiviral therapy on the prevention of HCC has
      been shown in a few randomized controlled trials. There is abundant evidence that
      antiviral therapy, in patients with long-term virological response, can improve
      liver histology, providing indirect support that antiviral therapy may prevent
      HCC by slowing progression of liver disease and possibly even reversing liver
      damage. Nevertheless, the risk of HCC remains in patients with chronic HBV or
      chronic HCV infection if treatment is initiated after cirrhosis is established.
      These data indicate that treatment might be of greater benefit if instituted
      earlier in the course of chronic hepatitis B or C. Safer, more effective, and
      more affordable antiviral therapies are needed for both hepatitis B and hepatitis
      C so more patients can benefit from treatment and more HCCs can be prevented.

PMID- 21070362
TI  - Birds and bees for biologists.

PMID- 21070363
TI  - Cautious optimism over Norway-Indonesia REDD pact.

PMID- 21070364
TI  - Surgical management of biliary complications following living donor liver
      transplantation.
AB  - BACKGROUND: Biliary complications (BC) account for much of the morbidities seen
      after living donor liver transplantation (LDLT). Surgical reconstruction might be
      necessary after the failure of endoscopic or percutaneous procedures. METHODS:  
      Between November 2002 and December 2009, a total of 76 LDLTs were performed. Six
      patients were excluded from statistical analysis because of early graft or
      patient loss. RESULTS: Of 70, 26 (37.1%) developed BC; 12 (46.2%) were
      successfully managed by non-surgical procedures, three (11.5%) died from BC
      related sepsis, one (3.8%) died from BC-unrelated causes, and 10 (38.5%)
      underwent surgical reconstruction. Of those 10, four patients had single duct
      reconstruction, five patients had double ducts reconstruction, and reconstruction
      was abandoned in one patient because of hepatic artery thrombosis. After a median
      follow-up period of 4.5 yr (0.1-6), seven (70%) remained well with no recurrent
      biliary problems, and three (30%) had recurrent BCs that were managed either
      conservatively or by retransplantation. Patients who underwent surgical
      reconstruction had significantly fewer hospital admissions, less need for
      invasive procedures, and shorter cumulative hospital stay (p < 0.05).
      CONCLUSIONS: In our experience, BCs after LDLT were frequently resistant to non
      surgical procedures. Surgical reconstruction is associated with fewer hospital
      admissions and less need for invasive procedures leading to reduced resources
      utilization.

PMID- 21070365
TI  - The renal benefit of mycophenolate mofetil after liver transplantation.
AB  - BACKGROUND: The risk and benefit of adding mycophenolate mofetil (MMF) to a
      standard immunosuppressive regimen at the time of liver transplantation (LT) is
      not well described. METHODS: We performed a retrospective case-control analysis
      comparing one-yr outcomes of all LT recipients at our institution treated with
      post-operative tacrolimus (TAC), MMF, and steroids vs. TAC and steroids. RESULTS:
      A total of 101 LT recipients (50:51 case:control) were analyzed. Despite more
      renal dysfunction at LT, the MMF + TAC group had similar serum creatinine (Cr)
      and glomerular filtration rate (GFR) as the TAC group one-yr post-LT. In this
      time period, Cr decreased (1.57-1.22 mg/dL, p = 0.04) and GFR increased (57.5
      65.1 mL/min per 1.73 m(2), p = 0.05) in the MMF + TAC group, while Cr increased
      (1.11-1.35, p < 0.01) and GFR declined (73.5-60.1, p < 0.001) in the TAC group.
      These findings occurred without a difference in absolute rejection episodes,
      hospitalizations, infections, deaths, or time to above events (p > 0.05).
      Subgroup analysis of patients stratified by pre-transplant renal dysfunction (Cr
      >= 1.2 mg/dL) supported the previous. MMF was reasonably well tolerated with a
      low rate of discontinuation. CONCLUSIONS: The use of adjunctive MMF immediately
      after LT may protect against calcineurin inhibitor nephrotoxicity, potentially
      without the need for dose reduction or increased risk of adverse events.

PMID- 21070366
TI  - Feasibility of tacrolimus, methotrexate, and prednisolone as a graft-versus-host
      disease prophylaxis in non-T-cell-depleted haploidentical hematopoietic stem cell
      transplantation for children.
AB  - In this study, we evaluated the feasibility of our graft-versus-host disease
      (GVHD) prophylaxis with tacrolimus, methotrexate, and prednisolone in non-T-cell
      depleted haploidentical hematopoietic stem cell transplantation (HSCT) for
      children. Twenty-one consecutive patients including those with hematological
      malignancies (n = 11), solid tumors (n = 7), and non-malignancies (n = 3) were
      analyzed. Myeloablative and reduced intensity conditionings were carried out in 5
      and 16 patients, respectively, and both of the regimens contained anti-human T
      lymphocyte immunoglobulin. Twenty (95%) of the 21 patients achieved primary
      engraftment. Acute GVHD of grades II-IV and III-IV were observed in nine (47%)
      and one (5%) patient, respectively, all of which were controllable by steroids.
      Chronic GVHD was observed in eight (51%) of the 17 evaluable patients, and one of
      them developed steroid refractory chronic GVHD. Treatment-related mortality
      occurred in three patients (15%), as a result of acute pancreatitis, chronic
      GVHD, and EB virus associated lymphoproliferative disease. The median follow-up
      of the 13 survivors was 24 months, and the two-yr probability of overall survival
      was 68%. The Karnofsky performance scale score of the 13 survivors was 100%.
      These results indicated the feasibility of our GVHD prophylaxis in non-T-cell
      depleted haploidentical HSCT for children.

PMID- 21070368
TI  - Pathology of the bone marrow and spleen in a case of
      myelodysplastic/myeloproliferative neoplasm associated with t(8;9)(p22;p24)
      involving PCM1 and JAK2 genes.

PMID- 21070367
TI  - Association of high anti-donor alloreactivity and low frequency of FoxP3
      expressing cells prior to kidney transplantation with acute graft rejection.
AB  - Acute rejection (AR) is an important factor for the development of chronic
      allograft dysfunction following kidney Tx. Identification of patients who would
      benefit from closer clinical surveillance to allow individual tailoring of
      immunosuppression and hence reducing the rate of AR is highly desired. Aim of
      this study was to investigate the association of pre-transplant alloreactivity
      and frequency of regulatory T cells (T(regs) ) with AR following living-donor
      kidney Tx. Peripheral blood mononuclear cells were isolated from 40 patients
      prior to Tx. T-cell alloreactivity against donor and third-party antigen was
      assessed by proliferative responses in mixed lymphocyte culture and enzyme linked
      immunospot technique. Pre-transplant frequency of CD4(+) CD25(+) CD127(low)
      FoxP3(+) T(regs) was determined by flow cytometry. Experimental data were
      correlated with occurrence of AR. We found that patients with rejection-free (RF)
      post-Tx courses showed significantly lower pre-transplant alloreactivity to donor
      antigen compared to individuals with borderline findings (BL) or AR. For RF
      patients, the proliferative T-cell responses to third-party antigen were
      significantly higher than for stimulation with donor cells whereas lymphocytes of
      the AR group showed the inverse pattern. A significantly higher expression of
      FoxP3 within the CD4(+) CD25(+) CD127(low) subset for RF and BL compared to the
      AR group was observed. In conclusion, pre-transplant anti-donor alloreactivity
      and FoxP3 expression within the CD4(+) CD25(+) CD127(low) subpopulation might
      prove useful to further define the patient's risk for AR.

PMID- 21070369
TI  - Hyperhomocysteinemia and the methylene tetrahydrofolate reductase C677T mutation
      in splanchnic vein thrombosis.
AB  - INTRODUCTION: The role that hyperhomocysteinemia (HH) and the C677T mutation in
      5,10-methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein
      thrombosis (SVT) remains unclear due to this unusual thrombotic location.
      OBJECTIVE: To analyse the possible association of HH with the C677T mutation in
      the MTHFR gene in SVT. MATERIAL AND METHODS: We determined homocysteine levels
      and the C677T MTHFR mutation, along with classical cardiovascular risk factors,
      in 48 patients with SVT (18 Budd-Chiari syndrome, 11 mesenteric vein thrombosis,
      19 portal vein thrombosis) and 84 controls. RESULTS: In the univariate analysis,
      patients with SVT showed statistically higher homocysteine levels (P =0.044).
      After adjusting for total cholesterol, differences disappeared (P =0.256).
      However, no differences in homocysteine levels were observed when comparing the
      three SVT types (P =0.199), even after adjusting for age and total cholesterol (P
      =0.095). In addition, the prevalence of the TT genotype was no different when
      controls were compared with patients with SVT (P =0.253) or with SVT subtypes (P
      =0.885). No association was found between HH (>15 MUm) and the TT genotype in
      cases (P =0.404), controls (P =0.178), or in the different SVT subtypes (P
      =0.495). CONCLUSIONS: Our results suggest that HH and the homozygous genotype in
      the MTHFR C677T mutation do not seem to play a role in SVT development.

PMID- 21070370
TI  - Cladribine combined with rituximab (R-2-CdA) therapy is an effective salvage
      therapy in relapsed or refractory indolent B-cell non-Hodgkin lymphoma.
AB  - Although cladribine has been reported to be an active purine analog against
      indolent B-cell non-Hodgkin lymphoma (B-NHL), there are few reports of
      combination use of cladribine and rituximab. This multicenter phase II study
      evaluated the efficacy and toxicity of cladribine with rituximab (R-2-CdA)
      therapy in relapsed or refractory indolent B-NHL. Twenty patients with the median
      age of 58.5 yrs (range, 42-72) were enrolled and received R-2-CdA therapy from
      April 2005 to July 2007. The median number of prior regimens was 2 (range, 1-3),
      and fifteen patients (75%) were previously treated with rituximab-containing
      regimens. Disease histology included follicular lymphoma in 16 patients, MALT
      lymphoma in two patients, nodal marginal B-cell lymphoma in one patient, and
      lymphoplasmacytic lymphoma in one patient. The overall response rate (ORR) was
      90%, with a complete response rate (CRR) of 70%. Estimated median progression
      free survival (PFS) time was 22.4 months (95%CI, 10.9-32.6 months) at a median
      follow-up time of 27 months (range, 12-43). Two-year PFS and 2-yr overall
      survival (OS) were 52.6% (95%CI, 31.0-73.2%) and 89.5% (95%CI, 66.1-97.3%),
      respectively. Grade 3 or grade 4 toxicities were neutropenia in 74% and
      thrombocytopenia in 11%. R-2-CdA therapy was demonstrated to have a high activity
      with durable PFS and acceptable toxicity in relapsed or refractory indolent B-NHL
      mostly pretreated with rituximab-containing therapy. Although a large-scale trial
      is needed for confirmation, R-2-CdA therapy could be a good salvage therapy
      option in relapsed or refractory indolent B-NHL.

PMID- 21070371
TI  - N-cadherin expression is correlated with metastasis of spindle cell carcinoma of
      head and neck region.
AB  - Spindle cell carcinoma (SpCC) is a biphasic tumor composed of conventional
      squamous cell carcinoma and a malignant spindle cell component. SpCC expresses
      both epithelial and mesenchymal markers by immunohistochemical analysis. There is
      mounting evidence for sarcomatoid transformation from the epithelial component,
      supporting the theory that SpCC is a monoclonal neoplasm originating from a stem
      cell giving rise to both components. The loss of E-cadherin and the gain of N
      cadherin expression are known as the "cadherin switching". Cadherin switching is
      a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial
      process in cancer progression providing cancer cells with the ability to escape
      from the primary focus, to invade stromal tissues, and to migrate to distant
      regions. Although E-cadherin down-regulation is well known in various cancers,
      there are a few studies on N-cadherin expression in cancer. Here, therefore, we
      investigated N-cadherin expression in the progression of head and neck SpCC.
      First, we examined cadherin switching in our established SpCC cell lines, SpCC-1
      and SpCC-2. SpCC-1 and SpCC-2 cells were spindle in shape and showed cadherin
      switching. Moreover, we examined N-cadherin expression in 15 SpCC cases by
      immunohistochemistry. Although N-cadherin expression was not observed in non
      neoplastic squamous epithelium, high expression of N-cadherin was observed in 10
      of 15 SpCC cases. Interestingly, 6 of 7 SpCC cases with metastasis showed high
      expression of N-cadherin. In conclusion, our findings suggest that N-cadherin may
      play an important role in metastasis of SpCC in addition to the pathogenesis of
      SpCC of the head and neck.

PMID- 21070372
TI  - After 10 years as Editor: some thoughts.

PMID- 21070373
TI  - Is ventilation duct cleaning useful? A review of the scientific evidence.
AB  - Ventilation duct cleaning (DC) is widely advocated to provide good indoor air
      quality (IAQ), health benefits, cost savings, and enhance ventilation system
      performance. The aim of the present review is to evaluate the scientific evidence
      as shown in the literature. There is evidence that under normal operating
      conditions, ventilation ducts can be contaminated with dusts and serve as
      reservoirs for microbials to proliferate. While controlled experiments noted that
      contaminants resuspension can elevate exposure levels indoors, no field studies
      have correlated poor IAQ with duct contamination. Despite high efficiencies of
      contaminant removal within the ducts during cleaning, reductions for different
      indoor air pollutants vary widely, where, post-cleaning air pollutants
      concentrations can be higher than pre-cleaning levels. Further, there are health
      concerns in the use of biocides, sealants and encapsulants. There is inadequate
      evidence to show that DC can improve airflow in ducts and reduce energy
      consumption. Although epidemiological studies indicate suggestive evidence that
      improperly maintained ducts are associated with higher risks of symptoms among
      building occupants, this review finds insufficient evidence that DC can alleviate
      occupant's symptoms. In summary, the need for duct cleanliness has to be properly
      balanced by the probable generation of indoor pollution resulting from DC and
      subsequent potential health risks. PRACTICAL IMPLICATIONS: Existing evidence is
      insufficient to draw solid conclusions regarding positive impact of duct cleaning
      on IAQ, health benefits, cost savings and HVAC performance. Maintaining duct
      cleanliness has to be properly balanced by the probable generation of indoor
      pollution and potential health risks.

PMID- 21070374
TI  - Modeled infiltration rate distributions for U.S. housing.
AB  - A set of 209 dwellings that represent 80% of U.S. housing stock is used to
      generate frequency distributions of residential infiltration rates. The set of
      homes is based on an analysis of the 1997 U.S. Department of Energy's Residential
      Energy Consumption Survey, which documents numerous housing characteristics
      including type, floor area, number of rooms, type of heating system, foundation
      type, and year of construction. The infiltration rate distributions are developed
      using the multizone network airflow model, CONTAM (CONTAMW 2.4 User Guide and
      Program Documentation, NISTIR 7251. National Institute of Standards and
      Technology.). In this work, 19 cities are selected to represent U.S. climatic
      conditions, and CONTAM simulations are performed for each of the 209 houses in
      these cities to calculate building air change rates for each hour over a year.
      Frequency distributions are then developed and presented nationally as well as
      based on house type and region. PRACTICAL IMPLICATIONS: These distributions will
      support indoor air quality, exposure, and energy analyses based on a truly
      representative collection of U.S. homes, which has previously not been possible.
      In addition, the methodology employed can be extended to other countries and
      other collections of buildings. For U.S.-specific analyses, these homes and their
      models, can be extended to include occupants, contaminant sources, and other
      building features to allow a wide range of studies to address other ventilation
      and indoor air quality issues.

PMID- 21070375
TI  - PVC--as flooring material--and its association with incident asthma in a Swedish
      child cohort study.
AB  - The Dampness in Buildings and Health study (DBH) started in the year 2000 in
      Varmland, Sweden, with a baseline questionnaire sent to all children (n = 14,077)
      aged 1-6. Five years later, a follow-up questionnaire was sent to the children
      who were 1-3 years at baseline. A total of 4779 children participated in both the
      baseline and the follow-up studies and constitute the study population in this
      cohort study. The aim of this study was to examine the association between
      exposure to PVC-flooring in the child's and parent's bedroom in homes of children
      aged 1-3 and the incidence of asthma, rhinitis, and eczema during the following 5
      year period. Adjusted analyses showed that the incidence of asthma among children
      was associated with PVC-flooring in the child's bedroom (AOR 1.52; 95% CI 0.99
      2.35) and in the parent's bedroom (1.46; 0.96-2.23). The found risks were on
      borderline of significance and should therefore be interpreted with caution.
      There was further a positive relationship between the number of rooms with PVC
      flooring and the cumulative incidence of asthma. PVC-flooring was found to be a
      stronger risk factor for incident asthma in multifamily homes when compared with
      single-family houses and in smoking families compared with non-smoking families
      and in women. PRACTICAL IMPLICATIONS: These longitudinal data from the DBH study
      found an association between the presence of PVC-flooring in the home and
      incident asthma in children. However, earlier results from the DBH study have
      shown that PVC-flooring is one important source for phthalates in indoor dust,
      and exposure to such phthalates was found to be associated with asthma and
      allergy among children. This emphasizes the need for prospective studies that
      focus on the importance of prenatal and neonatal exposure to phthalates in the
      development of asthma and allergy in children.

PMID- 21070376
TI  - Polycyclic and nitro musks in indoor air: a primary school classroom and a
      women's sport center.
AB  - Indoor air gas and particulate-phase samples (PM(2.5) ) were collected from a
      primary school classroom and a women's sport center because children are one of
      the sensitive population subgroups and women are frequent users of personal care
      products in addition to the high level of activity in this specific
      microenvironment. PM(2.5) was collected with a Harvard impactor, and polyurethane
      foam was used for the gas phase. Samples were ultrasonically extracted,
      concentrated, and analyzed with a GC-MS. The mean gas-phase concentrations in the
      classroom ranged from 0.12 +/- 0.2 ng/m(3) for MK to 267 +/- 56 ng/m(3) for HHCB,
      while it was from 0.08 +/- 0.10 ng/m(3) for AHMI to 144 +/- 61 ng/m(3) for HHCB
      in the sports center. Particulate-phase average concentrations in the sports
      center ranged from 0.22 +/- 0.11 ng/m(3) for ATII to 1.34 +/- 071 ng/m(3) for
      AHTN, while it ranged from 0.05 +/- 0.02 ng/m(3) (musk xylene) to 2.50 +/- 0.94
      ng/m(3) (HHCB) in the classroom. Exposure-risk assessment showed that inhalation
      route is most probably far less significant than the dermal route; however, it
      should be noted that the exposure duration covered in this study was not the
      larger fraction of the day. PRACTICAL IMPLICATIONS: Synthetic musk compounds
      (SMCs) are found everywhere because their use in household and personal care
      products (laundry detergents, carpet cleaners, cleaning agents, fabric softener
      soaps, shampoos, cosmetics, etc.) has been increasing. These compounds are semi
      volatiles that may result in direct and indirect exposures through inhalation
      route. Although SMCs were found to be dominant in the gas phase, exposure via
      inhalable particles may be important as we found several compounds in the
      particulate phase (PM(2.5)).

PMID- 21070377
TI  - Impact of temperature on the initial emittable concentration of formaldehyde in
      building materials: experimental observation.
AB  - The initial emittable concentration of volatile organic compounds (VOC) is a key
      parameter not only in evaluating the 'green' degree of building materials but
      also in modeling their emission characteristics. Although the impact of
      temperature on initial emittable concentration is important, it has not been
      reported in the literature. Using the multi-emission/flush regression method we
      developed, the impact of temperature on the initial emittable concentration of
      formaldehyde in medium density board has been experimentally studied. It is
      observed that the initial emittable concentration increases significantly with
      increasing temperature. When the temperature rises by 25.4 degrees C, it
      increases by about 507%. However, the initial emittable concentration at room
      temperature is far less than the value measured by the perforator method
      recommended by the Chinese National Standard GB/T 17657-1999, which measures the
      total concentration of formaldehyde in medium density board. This means most of
      formaldehyde in the building material cannot emit out at room temperature. The
      results will be very helpful in estimating the emission characteristics of
      building materials at different temperatures as well as for developing green
      building materials. PRACTICAL IMPLICATIONS: Knowledge of initial emittable
      concentration is important for VOC emission prediction. According to our
      experimental study, the initial emittable concentration is heavily dependent on
      temperature, and this factor should be considered in dealing with heating or
      cooling process of building materials. The significant difference between the
      initial emittable concentration and total concentration suggests that the total
      concentration seems not appropriate for judging the pollution level of building
      materials.

PMID- 21070378
TI  - Influence of abutment material on the gingival color of implant-supported all
      ceramic restorations: a prospective multicenter study.
AB  - PURPOSE: The aim of this clinical research on implant-supported restorations is
      to analyze, through spectrophotometric digital technology, the influence of the
      abutment material on the color of the peri-implant soft tissue. MATERIAL AND
      METHODS: Twenty patients received an endosseous dental implant in the anterior
      maxilla. At the time of each definitive prosthesis delivery, an all-ceramic crown
      has been tried on gold, titanium and zirconia abutment. After the insertion of
      each single abutment, the peri-implant soft tissue color has been measured
      through a spectrophotometer. Also, the thickness of the facial peri-implant soft
      tissue was measured at the level of the implant neck through a caliper. A
      specific software has been utilized to identify a specific tissue area and to
      collect the data before the statistical analysis in Lab* color space. The
      normality of the quantitative variables was verified by means of the Shapiro-Wilk
      test. Simple linear correlation between quantitative variables was evaluated by
      using Pearson's coefficient. The results on the performance of the abutment
      materials with regard to the color measurements and the overall measurement
      DeltaE were described by computing the least-square means. The significance of
      differences among types of abutment was verified by means of the Scheffe test for
      multiple comparisons. RESULTS: For all the abutments used, the color of the peri
      implant soft tissue appeared to be significantly different from the one of the
      contra-lateral tooth (DeltaE>8.5). Significantly higher (P<0.05) difference were
      present with the use of titanium abutments (11 +/- 0.4) when compared with the
      results of gold (8.9 +/- 0.4) and zirconia (8.5 +/- 0.4) abutments. No
      correlation has been demonstrated between soft tissue thickness and degree of
      color difference (P>0.25). CONCLUSIONS: Within the limitation of the present
      study, the peri-implant soft tissue color appears to be different from the soft
      tissue color around natural teeth, no matter which type of restorative material
      is selected. When titanium abutment was selected, significantly higher
      differences were present than those obtained with gold or zirconia abutments. The
      thickness of the peri-implant soft tissue did not appear to be a crucial factor
      in the abutment impact on the soft tissue color.

PMID- 21070379
TI  - Intra-oral bone harvesting: two methods compared using histological and
      histomorphometric assessments.
AB  - AIM: This study used morphometric analyses to compare two methods for the intra
      oral harvesting of particulate bone: Mectron Piezosurgery(r) and the Meta
      Micross(r). MATERIALS AND METHODS: Twenty patients requiring bilateral germectomy
      of the lower third molars for orthodontic reasons were selected and a sample was
      harvested from each patient from a standardised donor site (the cortical bone in
      the area of the retromolar triangle). Ten samples were obtained for each method.
      The particulate collected were subjected to a histological examination and the
      samples were analysed considering the following parameters: the mean surface area
      of fragments, the mean surface area considered vital and the mean surface area
      considered non-vital, the mean percentage of area considered vital and the mean
      percentage of area considered non-vital, the mean number of normal osteocytes and
      the mean number of osteocytes with morphological changes identified per unit area
      (600,000 MUm(2)). The results were analysed, calculating the mean and the
      corresponding standard deviations, and testing their significance using Student's
      t-test, and plotted in graphs. RESULTS: Mectron Piezosurgery(r) produced
      significantly larger particles (P<0.05) than the Meta Micross(r), with a larger
      mean surface area considered vital and a significantly larger (P<0.05) surface
      area considered non-vital. Mectron Piezosurgery(r) also produced a smaller mean
      percentage of area considered vital (64.83%) and a larger mean percentage of area
      considered non-vital (35.17%) by comparison with the Meta Micross(r) (75.34% and
      24.66%, respectively). The data also showed that the two methods produce a
      similar quantity of empty lacunae, and that the Mectron Piezosurgery(r) produces
      a larger quantity of osteocytes. CONCLUSIONS: The analyses conducted demonstrated
      that the particulate collected with the Meta Micross(r) had a smaller mean
      surface area of the fragments and a smaller surface area of bone considered non
      vital than in the particulate collected using Mectron Piezosurgery(r).

PMID- 21070380
TI  - Influence of surface roughness and shape on microdamage of the osseous surface
      adjacent to titanium dental implants.
AB  - OBJECTIVES: To assess the relationship between smooth and roughened implant
      surfaces of straight and narrow configurations with respect to microdamage of the
      bone surface during placement of dental implants. MATERIALS AND METHODS: Straight
      and tapered, rough and smooth surface Nobel Biocare implants were placed into
      sheep mandibles. Microdamage within the bone adjacent to the implant surface was
      quantitated using a semi-automated digitized histomorphometric method. RESULTS:
      Independent of implant type, microdamage, microcracks, cross-hatch damage and
      diffuse damage were significantly higher close to the implants compared with far
      from the implants. Microcracks and cross-hatch damage were higher for the rough
      cylindrical implants than all the other implant types. CONCLUSIONS: Insertion of
      a rough cylindrical implant type results in an increased fraction of microdamaged
      bone matrix in comparison to rough tapered, smooth cylindrical and smooth tapered
      implants.

PMID- 21070381
TI  - Bone reaction adjacent to microplasma-sprayed calcium phosphate-coated oral
      implants subjected to an occlusal load, an experimental study in the dog.
AB  - BACKGROUND: A new microplasma spraying equipment (MSE) to deposit calcium
      phosphate (CaP) ceramic coatings onto titanium substrates has been developed.
      With this system, it is possible to spray fine particles and to apply textured
      hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat
      power of the microplasma jet, overheating of the powder particles as well as
      excessive local overheating of the substrate are diminished. Furthermore, because
      of the small laminar plasma jet, it is possible to achieve high spray efficiency
      in the case of spraying for dental implants. Also, the low level of noise (25-50
      dB) and hardly any dust makes it possible to operate MSE under conditions of
      normal workrooms. OBJECTIVE: The aim was to investigate, in a mandibular dog
      model, the effect of functional load on soft-tissue adaptation as well as crestal
      bone-level changes around titanium implants provided with newly developed
      microplasma-sprayed CaP coatings. MATERIAL AND METHODS: For histomorphometrical
      evaluation, 56 screw-type titanium implants were inserted into the mandibles of
      seven adult Beagle dogs. The implants were either acid etched without an
      additional coating, coated with a conventionally plasma-sprayed CaP ceramic (PS),
      coated with a microplasma-sprayed CaP ceramic (MPS) or with a microplasma-sprayed
      coating at only the apical part (aMPS). To assess the effect of occlusal loading,
      a split-mouth design was used. Six weeks after implantation, the implants in one
      half of the mandible of each dog were functionally loaded whereas the contra
      lateral implants served as control. One year after loading, the animals were
      sacrificed. Soft-tissue dimension as well as marginal bone level were
      histologically assessed. RESULTS: Histometric analysis of undecalcified
      histologic sections included the evaluation of the sulcus depth, the dimension of
      the junctional epithelium and the connective tissue as well as the first bone-to
      implant contact. For MPS-surfaced implants, functional loading was associated
      with--compared with the non-loaded state--unchanged soft-tissue dimension.
      Furthermore, the soft-tissue dimension did not differ from the dimensions around
      non-coated, PS and aMPS implants. Moreover, the first bone-to-implant contact was
      not significantly altered by functional loading and comparable non-coated, PS and
      aMPS implants. CONCLUSION: Within the limits of the experiment, we conclude that,
      in comparison, functional loading does not affect the marginal soft-tissue
      response to MPS CaP-coated implants. However, in comparison, functional loading
      might affect marginal bone response to MPS CaP-coated implants.

PMID- 21070382
TI  - Long-term prosthetic aftercare of direct vs. indirect attachment incorporation
      techniques to mandibular implant-supported overdenture.
AB  - OBJECTIVE: The aim of this long-term study was to compare the need for prosthetic
      aftercare of direct vs. indirect attachment incorporation techniques to
      mandibular implant-supported overdenture. MATERIALS AND METHODS: Forty-five
      consecutive patients were included (130 implants were placed). Treatment was
      randomly allocated, resulting in 22 patients (group A) to be treated with direct
      ball attachment incorporation and 23 patients (group B) to be treated with
      indirect ball attachment incorporation. All patients were treated by experienced
      oral-maxillofacial surgeons/periodontists and experienced
      prosthodontists/residents. From the first day that the patients visited the
      clinic up to 20 years after the first treatment session, all surgical or
      prosthetic therapeutic interventions were recorded. The recorded data for the
      present study included the number of aftercare visits and dental treatment
      received (pressure sores relieve, liner changes due to loss of retention and
      attachment replacement due to wear). RESULTS: The mean follow-up was 93+/-57
      months. No implants were lost. Statistical analysis revealed a statistically
      significantly (P<0.001) greater need for prosthetic interventions in group B vs.
      group A. The mean number of visits dedicated to - pressure sores relieve (7.04+/
      1.4 vs. 3.63+/-0.84); liner exchange due to loss of retention (3.6+/-1.3 vs.
      1.09+/-1.06) was significantly higher in group B. Attachment replacement due to
      wear occurred only in group B (11/23 - 47.8%). CONCLUSION: The direct technique
      for attachment incorporation in mandibular implant-supported overdentures using
      ball attachments is superior to the indirect technique from the aftercare
      perspective during a long-term evaluation period.

PMID- 21070383
TI  - Chemical modification of an implant surface increases osteogenesis and
      simultaneously reduces osteoclastogenesis: an in vitro study.
AB  - OBJECTIVES: The present study investigated the effect of a chemical modification
      of the SLA surface (SLActive surface) on human periodontal ligament (hPDL) cell
      (1) adhesion, (2) proliferation, (3) osteogenic differentiation (core binding
      factor alpha-1 [Cbfa-1], bone morphogenetic protein-7 [BMP-7] gene expression and
      alkaline phosphatase [ALP] activity) and (4) osteoclast formation and activity
      (osteoprotegerin [OPG] and receptor activator of nuclear factor-kappa B ligand
      [RANKL] gene expression). The above activities were based on the hypothesis that
      the expression of such molecules might be dependent on the characteristics of the
      implant surface. MATERIAL AND METHODS: hPDL cells were isolated and characterized
      for their mesenchymal origin, fibroblastic and osteoblastic phenotype. hPDL cells
      were cultured on smooth, SLA and SLActive implant surfaces (chemically modified).
      Cell attachment and proliferation were assessed for 5, 24, 72 h, 5 and 7 days.
      Cbfa-1, BMP-7, OPG and RANKL gene expression was assessed by RT-PCR and a
      colorimetric assay for ALP activity was applied. RESULTS: hPDL cells grown on
      SLActive surfaces demonstrated increased proliferation rates (24 h, 5 and 7 days
      of the incubation period), and ALP activity was found to be significantly
      upregulated (5, 72 h and 7 days) as compared with the SLA surfaces. After 7 days
      of culture, the gene expression of BMP-7, Cbfa-1 and OPG by hPDL cells was
      significantly upregulated, while RANKL gene expression was significantly
      downregulated in response to the SLActive surface. CONCLUSION: Chemical
      modification of a previously roughened implant surface increases hPDL
      proliferation and upregulates osteoblastic differentiation. It can also suppress
      osteoclastogenesis regulating the RANKL-RANK-OPG axis. Hence, an osteoprotective
      microenvironment is created around chemically modified implants that may enhance
      osseointegration.

PMID- 21070385
TI  - Virulence factor cytotoxin-associated gene A in Helicobacter pylori is
      downregulated by interferon-gamma in vitro.
AB  - Helicobacter pylori-infected gastric mucosa is characterized by high levels of
      interferon-gamma (IFN-gamma), but whether the high level of IFN-gamma regulates
      the virulence of H. pylori is unclear. Here, we characterized the response of H.
      pylori to IFN-gamma and found by indirect immunofluorescence that IFN-gamma can
      bind to H. pylori. The binding resulted in the altered expression of 14 proteins,
      including the virulence factor, cytotoxin-associated gene A (CagA), whose
      expression was downregulated. The transcription and translation of CagA
      downregulated by IFN-gamma was further confirmed by reverse transcriptase-PCR and
      Western blot analysis. We co-cultured the human gastric cancer cell line AGS with
      H. pylori exposed to IFN-gamma; both phosphorylated CagA and nonphosphorylated
      CagA in AGS cells were downregulated by IFN-gamma, and the proportion of cells
      with the 'hummingbird' phenotype was also decreased. Thus, IFN-gamma can help
      control H. pylori infection indirectly through the virulence factor CagA.

PMID- 21070384
TI  - Prognostic significance of preoperative serum CYFRA 21-1 in patients with upper
      urinary tract urothelial carcinoma.
AB  - OBJECTIVES: The prognosis for upper urinary tract urothelial carcinoma is
      generally poorer than that for bladder cancer, and prognostic predictors with a
      high specificity for upper urinary tract urothelial carcinoma (UUT-UC) are needed
      to optimize treatment. In fact, the only preoperative predictor currently
      available is C-reactive protein. In the present study, we investigated the
      usefulness of pretreatment serum CYFRA 21-1 as a new prognostic predictor in UUT
      UC. METHODS: A total of 45 UUT-UC patients for whom serum CYFRA 21-1 was measured
      before treatment were included in this retrospective analysis. Patients were
      separated into high and low serum CYFRA 21-1 groups based on a cut-off value of
      2.7 ng/mL determined from a receiver operating characteristic curve. Kaplan-Meier
      survival curves were calculated and the overall survival rate was statistically
      analyzed for the high and low pretreatment serum CYFRA 21-1 groups using the log
      rank test. Multivariable analysis was carried out using the Cox proportional
      hazards analysis. RESULTS: By the median follow-up period of 14.4 months, 20
      patients (44.4%) had died. Of the 45 patients, 23 (51.1%) were in the high
      pretreatment serum CYFRA 21-1 group, and the overall survival rate of this group
      was significantly lower (P < 0.001). Multivariable analysis identified only
      distant metastasis (P < 0.001) and pretreatment serum CYFRA 21-1 (P = 0.039) as
      independent prognostic predictors. Distant metastasis did not significantly
      differ between the two groups or correlate with pretreatment serum CYFRA 21-1.
      CONCLUSION: These findings suggest that pretreatment serum CYFRA 21-1 values
      could serve as a prognostic predictor of UUT-UC.

PMID- 21070386
TI  - Quinolone/fluoroquinolone susceptibility in Escherichia coli correlates with
      human polymicrobial bacteriuria and with in vitro interleukine-8 suppression.
AB  - Urinary tract infections (UTIs) are frequently polymicrobial diseases mainly
      sustained by Escherichia coli in association with other opportunistic pathogens.
      Cystitis and pyelonephritis are usually accompanied by an inflammatory response,
      which includes neutrophil recruitment. Uropathogenic E. coli possess the ability
      to evade host defenses, modulating the innate immune response. The aim of this
      study was to determine whether particular E. coli strains correlate with
      polymicrobial bacteriuria and whether escape from the early host defenses and
      microbial synergy could lead to mixed UTIs. We evaluated 188 E. coli-positive
      urine samples and assessed the relationships among polymicrobism, neutrophil
      presence and several traits of E. coli isolates (virulence factors such as hlyA,
      fimA, papC and their relative products, i.e. hemolysin, type 1 and P fimbriae,
      and cnf1, their phylogenetic group) and their ability to suppress cytokine
      response in 5637 bladder epithelial cells. Escherichia coli susceptibility toward
      quinolones and fluoroquinolones, known to be linked to the pathogenicity of this
      species, was also considered. We found significant correlations among
      polymicrobial bacteriuria, absence of pyuria and quinolone/fluoroquinolone
      susceptibility of E. coli isolates and their enhanced capability to suppress
      interleukin-8 urothelial production when compared with the patterns induced by
      the resistant strains.

PMID- 21070387
TI  - Hepatic arterial embolization for massive bleeding from an intrahepatic artery
      pseudoaneurysm using N-butyl-2-cyanoacrylate after living donor liver
      transplantation.
AB  - Parenchymal pseudoaneurysm of the hepatic arteries with massive intraperitoneal
      bleeding is rare but a serious life-threatening complication when it occurs
      following liver transplantation. We report a case of an adult postliving donor
      liver transplant recipient who developed massive subcapsular bleeding combined
      with massive right pleural effusion from ruptured multiple small intrahepatic
      arteries, which developed from a pseudoaneurysm that was treated by hepatic
      arterial embolization. Successful embolization was performed via a percutaneous
      trans-catheter approach by depositing 20-25%N-butyl-2-cyanoacrylate (NBCA)
      through the multiple small intrahepatic arteries into the pseudoaneurysm.
      Complete occlusion of the feeding arteries and pseudoaneurysm cavity resulted to
      immediate cessation of bleeding. There was no re-bleeding; and normal liver graft
      function was noted postembolization. Hepatic arterial embolization with NBCA can
      be used as treatment for postliver transplant peripheral intrahepatic artery
      pseudoaneurysm bleeding.

PMID- 21070388
TI  - Glutamate transporter EAAT4 in Purkinje cells controls intersynaptic diffusion of
      climbing fiber transmitter mediating inhibition of GABA release from
      interneurons.
AB  - Neurotransmitters diffuse out of the synaptic cleft and act on adjacent synapses
      to exert concerted control of the synaptic strength within neural pathways that
      converge on single target neurons. The excitatory transmitter released from
      climbing fibers (CFs), presumably glutamate, is shown to inhibit gamma
      aminobutyric acid (GABA) release at basket cell (BC)-Purkinje cell (PC) synapses
      in the rat cerebellar cortex through its extrasynaptic diffusion and activation
      of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on
      BC axon terminals. This study aimed at examining how the CF transmitter-diffusion
      mediated presynaptic inhibition is controlled by glutamate transporters.
      Pharmacological blockade of the PC-selective neuronal transporter EAAT4 markedly
      enhanced CF-induced inhibition of GABAergic transmission. Tetanic CF-stimulation
      elicited long-term potentiation of glutamate transporters in PCs, and thereby
      attenuated the CF-induced inhibition. Combined use of electrophysiology and
      immunohistochemistry revealed a significant inverse relationship between the
      level of EAAT4 expression and the inhibitory action of CF-stimulation on the GABA
      release at different cerebellar lobules - the CF-induced inhibition was profound
      in lobule III, where the EAAT4 expression level was low, whereas it was minimal
      in lobule X, where EAAT4 was abundant. The findings clearly demonstrate that the
      neuronal glutamate transporter EAAT4 in PCs plays a critical role in the
      extrasynaptic diffusion of CF transmitter - it appears not only to retrogradely
      determine the degree of CF-mediated inhibition of GABAergic inputs to the PC by
      controlling the glutamate concentration for intersynaptic diffusion, but also
      regulate synaptic information processing in the cerebellar cortex depending on
      its differential regional distribution as well as use-dependent plasticity of
      uptake efficacy.

PMID- 21070389
TI  - Different circuit and monoamine mechanisms consolidate long-term memory in
      aversive and reward classical conditioning.
AB  - There has been considerable recent interest in comparing the circuit and
      monoamine-based mechanisms of aversive and reward-associative conditioning in a
      number of vertebrate and invertebrate model systems. The mollusc Lymnaea
      stagnalis provides a unique opportunity to explore changes in the neural and
      chemical pathways underlying these two different types of conditioning as its
      feeding circuitry has been thoroughly characterised. Animals can learn after a
      single trial to associate the same CS (amyl acetate) either with a punishment
      (quinine) or reward (sucrose), showing either a reduced or an elevated feeding
      response, respectively, to the CS. We previously showed that reward conditioning
      strengthened the direct excitatory pathway from the lips to the feeding central
      pattern generator in the buccal ganglia through the activation of feeding
      interneurons in the cerebral ganglia. Now we demonstrate that aversive
      conditioning enhances the strength of a different inhibitory pathway that
      suppresses feeding but has no effect on the excitatory pathway. Here we show that
      consolidation of long-term memory (LTM) in reward conditioning depends on
      dopamine but not octopamine. In contrast, aversive LTM depends on octopamine but
      not dopamine. Octopamine is the invertebrate equivalent of noradrenalin, so these
      results on the monoamine dependence of reward and aversive conditioning in
      Lymnaea resemble, at the transmitter receptor level, those in mammals but are the
      opposite of those in another invertebrate group, the insects.

PMID- 21070391
TI  - Thyroid hormone induces cerebellar neuronal migration and Bergmann glia
      differentiation through epidermal growth factor/mitogen-activated protein kinase
      pathway.
AB  - Cerebellar development in the postnatal period is mainly characterized by an
      intense cellular proliferation in the external granular layer, followed by
      migration of granular cells in the molecular layer along the Bergmann glia (BG)
      fibers. Cerebellar ontogenesis undergoes dramatic modulation by thyroid hormones
      (THs), although their mechanism of action in this organ is still largely unknown.
      We previously demonstrated that THs induce astrocytes to secrete epidermal growth
      factor (EGF), which thus promotes cerebellar neuronal proliferation and
      extracellular matrix remodeling in vitro. In the present study, we investigated
      the effect of the TH/EGF pathway on granule neuronal migration. By taking
      advantage of rat explant and dissociated culture assays, we showed that
      cerebellar astrocytes treated with TH promote granule cell migration. The
      addition of neutralizing antibodies against EGF or the pharmacological inhibitor
      of EGF signaling, bis-tyrphostin, completely inhibited TH-astrocyte-induced
      migration. Likewise, the addition of EGF itself greatly increased neuronal
      migration. Treatment of BG-dissociated cultures by EGF dramatically induced an
      alteration in cell morphology, characterized by an elongation in the glial
      process. Both neuronal migration and BG elongation were inhibited by the mitogen
      activated protein kinase pathway inhibitor PD98059, suggesting that these events
      might be associated. Together, our results suggest that, by inducing EGF
      secretion, THs promote neuronal migration through BG elongation. Our data provide
      new clues to the molecular mechanism of THs in cerebellar development, and may
      contribute to a better understanding of some neuroendocrine disorders associated
      with migration deficits.

PMID- 21070390
TI  - Activation of the central serotonergic system in response to delayed but not
      omitted rewards.
AB  - The forebrain serotonergic system is a crucial component in the control of
      impulsive behaviours. However, there is no direct evidence for natural serotonin
      activity during behaviours for delayed rewards as opposed to immediate rewards.
      Herein we show that serotonin efflux is enhanced while rats perform a task that
      requires waiting for a delayed reward. We simultaneously measured the levels of
      serotonin and dopamine in the dorsal raphe nucleus using in vivo microdialysis.
      Rats performed a sequential food-water navigation task under three reward
      conditions: immediate, delayed and intermittent. During the delayed reward
      condition, in which the rat had to wait for up to 4 s at the reward sites, the
      level of serotonin was significantly higher than that during the immediate reward
      condition, whereas the level of dopamine did not change significantly. By
      contrast, during the intermittent reward condition, in which food was given on
      only about one-third of the site visits, the level of dopamine was lower than
      that during the immediate reward condition, whereas the level of serotonin did
      not change significantly. Dopamine efflux, but not serotonin efflux, was
      positively correlated with reward consumption during the task. There was no
      reciprocal relationship between serotonin and dopamine. This is the first direct
      evidence that activation of the serotonergic system occurs specifically in
      relation to waiting for a delayed reward.

PMID- 21070393
TI  - Origins of multisynaptic projections from the basal ganglia to rostrocaudally
      distinct sectors of the dorsal premotor area in macaques.
AB  - We examined the organization of multisynaptic projections from the basal ganglia
      (BG) to the dorsal premotor area in macaques. After injection of the rabies virus
      into the rostral sector of the caudal aspect of the dorsal premotor area (F2r)
      and the caudal sector of the caudal aspect of the dorsal premotor area (F2c),
      second-order neuron labeling occurred in the internal segment of the globus
      pallidus (GPi) and the substantia nigra pars reticulata (SNr). Labeled GPi
      neurons were found in the caudoventral portion after F2c injection, and in the
      dorsal portion at the rostrocaudal middle level after F2r injection. In the SNr,
      F2c and F2r injections led to labeling in the caudal or rostral part,
      respectively. Subsequently, third-order neuron labeling was observed in the
      external segment of the globus pallidus (GPe), the subthalamic nucleus (STN), and
      the striatum. After F2c injection, labeled neurons were observed over a broad
      territory in the GPe, whereas after F2r injection, labeled neurons tended to be
      restricted to the rostral and dorsal portions. In the STN, F2c injection resulted
      in extensive labeling over the nucleus, whereas F2r injection resulted in
      labeling in the ventral portion only. After both F2r and F2c injections, labeled
      neurons in the striatum were widely observed in the striatal cell bridge region
      and neighboring areas, as well as in the ventral striatum. The present results
      revealed that the origins of multisynaptic projections to F2c and F2r in the BG
      are segregated in the output stations of the BG, whereas intermingling rather
      than segregation is evident with respect to their input station.

PMID- 21070394
TI  - MiR-138 inhibits EZH2 methyltransferase expression and methylation of histone H3
      at lysine 27, and affects thermotolerance acquisition.
AB  - Thermotolerance acquisition involves neuronal network remodeling and, hence,
      alteration in the repertoire of expressed proteins. We have previously
      demonstrated the role of histone H3 methylation at lysine 27 (H3K27) by EZH2
      methyltransferase in the regulation of gene expression during the critical period
      for the establishment of thermal control in chicks. Here we describe another
      level of biological regulation, demonstrating the inhibitory role of microRNAs
      (miRNAs) in the regulation of EZH2 expression in thermoregulatory system
      development and functioning. During heat conditioning in the critical period for
      the establishment of thermal control, a decrease in expression of the EZH2
      targeting miR-138 occurred simultaneously with an increase in EZH2 levels in the
      preoptic anterior hypothalamus. Intracranial injection of miR-138 during the
      critical period led to a transient reduction in EZH2 levels, which was
      accompanied by a decrease in H3K27 methylation. Injection of miR-138 followed by
      heat conditioning also abolished EZH2 induction during heat conditioning.
      Moreover, this miR-138-induced inhibition of EZH2 during the critical period
      resulted in a long-term effect on EZH2 expression. A week after the treatment,
      the EZH2 protein levels in conditioned and in nonconditioned chicks were
      different from those in their saline-injected counterparts and the directions of
      change were opposite to each other. Finally, miR-138 injection during the
      critical period disrupted the establishment of thermoregulation, manifested as a
      defective body temperature response to heat. These data demonstrate a role for
      miRNAs in regulating the expression of histone-modifying enzymes, and thus
      emphasize the multilevel regulation mechanism which includes both epigenetic and
      miRNA regulatory mechanisms in neuronal network organization during the critical
      period of sensory development.

PMID- 21070395
TI  - Preparation and performance of obstacle steps: interaction between brain and
      spinal neuronal activity.
AB  - This study investigated the interactions of supraspinal with spinal neuronal
      circuits during obstacle steps by recordings of electroencephalography (EEG),
      reflex activity and limb muscle electromyography (EMG). Subjects walking with
      reduced vision on a treadmill were acoustically informed about an approaching
      obstacle and received feedback about task performance. Only following a task
      relevant acoustic signal, spinal reflex responses, evoked by tibial nerve
      stimulation during mid-stance, were enhanced in proximal arm and leg flexor
      muscles prior to obstacle compared to normal swing, reflecting the neuronal
      preparation of the task. During swing over the obstacle, limb muscle EMG activity
      was greater than in normal swing. Both the preparation and the performance (i.e.
      ascending movement slope of the obstacle-crossing leg) were associated with an
      enhanced EEG signal mainly in the prefrontal cortex of the right hemisphere.
      Adaptational changes in performance, reflex activity and muscle activation during
      repetitive obstacle stepping were not reflected in the EEG activity, probably due
      to an insufficient resolution of the EEG. The observations suggest that drive
      from supraspinal centers initiates and maintains spinal neuronal activity
      underlying obstacle task preparation and performance.

PMID- 21070396
TI  - Hypothalamic transcriptome plasticity in two rodent species reveals divergent
      differential gene expression but conserved pathways.
AB  - We have addressed the question of how different rodent species cope with the life
      threatening homeostatic challenge of dehydration at the level of transcriptome
      modulation in the supraoptic nucleus (SON), a specialised hypothalamic
      neurosecretory apparatus responsible for the production of the antidiuretic
      peptide hormone arginine vasopressin (AVP). AVP maintains water balance by
      promoting water conservation at the level of the kidney. Dehydration evokes a
      massive increase in the regulated release of AVP from SON axon terminals located
      in the posterior pituitary, and this is accompanied by a plethora of changes in
      the morphology, electrophysiological properties, biosynthetic and secretory
      activity of this structure. Microarray analysis was used to generate a definitive
      catalogue of the genes expressed in the mouse SON, and to describe how the gene
      expression profile changes in response to dehydration. Comparison of the genes
      differentially expressed in the mouse SON as a consequence of dehydration with
      those of the rat has revealed many similarities, pointing to common processes
      underlying the function-related plasticity in this nucleus. In addition, we have
      identified many genes that are differentially expressed in a species-specific
      manner. However, in many cases, we have found that the hyperosmotic cue can
      induce species-specific alterations in the expression of different genes in the
      same pathway. The same functional end can be served by different means, via
      differential modulation, in different species, of different molecules in the same
      pathway. We suggest that pathways, rather than specific genes, should be the
      focus of integrative physiological studies based on transcriptome data.

PMID- 21070397
TI  - Gut permeability and food allergies.
AB  - Intestinal permeability is a critical feature of the gastrointestinal epithelium
      as it must allow an efficient passage of nutrients and restrict the entry of
      larger molecules, such as protein antigen, in order to facilitate appropriate
      immune responses towards food antigens. The proper regulation of the epithelial
      barrier relies on multiple, intricate physiological and immunologic mechanisms,
      in terms of which recent progresses regarding the cellular and molecular
      components have been unravelled. In genetically predisposed individuals,
      breakdown of oral tolerance can occur, leading to the inadequate production of
      allergen-specific IgE and the recruitment of mast cells in the gastrointestinal
      mucosa. Under such conditions, the intestinal permeability towards allergen is
      altered via different mechanisms, with IgE-CD23-mediated transport across the
      mucosa playing an important amplification role. Additionally, during the effector
      phase of the allergic reaction, when mast cells degranulate, a series of
      inflammatory mediators, such as proteases and cytokines, are released and further
      affects intestinal permeability. This leads to an increase in the passage of
      allergens and hence contributes to perpetuate the inflammatory reaction. In this
      review, we describe the importance of properly balanced intestinal permeability
      in oral tolerance induction and address the processes involved in damaging the
      intestinal barrier in the sensitized epithelium and during allergic reactions. We
      conclude by speculating on the effect of increased intestinal permeability on the
      onset of sensitization towards dietary antigens.

PMID- 21070399
TI  - Strategies to reduce transfusion acquired vCJD.
AB  - Variant Creutzfeldt-Jakob disease (vCJD) can be transmitted by transfusion. The
      risk depends on the number of infected donors in the community. An estimate of
      these numbers in a less genetically susceptible population, based on the epidemic
      seen so far, suggests a maximum of 300 more cases. From this, it is possible to
      predict a maximum of one transfusion acquired case in 3 years from plasma
      transfusion. Importation of plasma from outside the UK has been advocated to
      prevent these cases and would cost around L30 million per year. An alternative
      measure is to use the observed susceptibility and exposure to dietary vCJD by
      age, and to target low risk donors for the production of components such as fresh
      frozen plasma (FFP) and platelets. This will reduce the possible cases of plasma
      transfusion-acquired vCJD at little or no extra cost to the health service.

PMID- 21070398
TI  - Association of thromboxane A2 receptor (TBXA2R) gene polymorphism in patients
      with aspirin-intolerant acute urticaria.
AB  - BACKGROUND: The thromboxane A2 receptor (TBXA2R) is a potent broncho- and vaso
      constrictor and is associated with leukotriene synthesis. Polymorphisms in the
      TBXA2R gene have been linked to atopy, asthma, and atopic dermatitis. This study
      evaluated the association between genetic TBXA2R variants and the development of
      acetyl salicylic acid (ASA)-intolerant acute urticaria (AIAU). METHODS: AIAU
      patients (n=167), ASA-intolerant chronic urticaria (AICU) patients (n=149), and
      healthy controls (NC) (n=265) were included. All patients were enrolled at Ajou
      University Hospital in Suwon, Korea. Two TBXA2R polymorphisms (-4684T>C and
      795T>C) were genotyped by primer extension using a SNAPshot ddNTP primer
      extension kit. Luciferase activity was measured using a dual-luciferase reporter
      assay kit. An electrophoretic mobility shift assay (EMSA) was performed using a
      nuclear extract from a human mast cell line (HMC-1). RESULTS: Genetic association
      data demonstrated that compared with NC subjects, AIAU patients had a
      significantly higher frequency of the homozygous TT genotype of TBXA2R-4684T>C
      (P=0.005, P(corr) =0.03). No differences were identified between the AICU and the
      NC groups. Luciferase activity, reflecting promoter activity, was significantly
      lower with the TBXA2R-4684T-containing construct than with the -4684C-containing
      construct (P<0.001); the activity decreased further upon co-transfection with ETS
      like gene transcription factor-1 (ELK-1) (P=0.012). EMSA revealed that the -4684T
      allele produced a specific shifted band, with a greater affinity than that
      produced by the -4684C allele. CONCLUSION AND CLINICAL RELEVANCE: These results
      suggest that the TBXA2R-4684T allele may be associated with lower TBXA2R
      expression, which may contribute to the development of the AIAU phenotype.

PMID- 21070400
TI  - Effect of an anti-inflammatory dose of prednisone on thyroid hormone monitoring
      in hypothyroid dogs.
AB  - It is not uncommon for a hypothyroid dog to be receiving concurrent
      corticosteroids. As hypothyroid dogs receiving thyroid supplement need periodic
      monitoring, knowledge of whether prednisone alters thyroid hormone concentrations
      would be useful to determine whether testing can or should be done while the dog
      is receiving therapy and whether dose adjustments are appropriate. In this study,
      the effect of short-term anti-inflammatory prednisone was determined in dogs with
      naturally occurring hypothyroidism. Eight adult dogs were given prednisone (1.0
      mg/kg, orally) daily for 7 days and then on alternate days for 14 days. Serum
      total thyroxine (T(4) ), free T(4) (fT(4) ), and thyroid-stimulating hormone
      (TSH) were measured on days 7, 21 and 28 and compared with baseline data. Total
      T(4) concentrations were significantly decreased after 7 days of anti
      inflammatory prednisone, but were not significantly altered from baseline on days
      21 or 28. Free T(4) and TSH concentrations were not significantly altered from
      baseline at any point during the study. Two dogs had decreased total T(4)
      concentrations on day 7, which may have resulted in an alteration in thyroid
      supplementation. Results showed that administration of prednisone at a dosage of
      1 mg/kg, orally, once daily for 7 days decreased total T(4) , while fT(4) was
      unchanged, suggesting that fT(4) may be less affected by daily prednisone
      administration. Anti-inflammatory doses of prednisone administered every other
      day did not interfere with thyroid hormone monitoring.

PMID- 21070401
TI  - Evaluation of the agreement between allergen-specific intradermal or IgE
      serological tests and a point-of-care immunodot assay in dogs with atopic
      dermatitis.

PMID- 21070402
TI  - Expression of CD176 (Thomsen-Friedenreich antigen) on lung, breast and liver
      cancer-initiating cells.
AB  - The cancer-initiating capacity of most malignant tumours is considered to reside
      in a small subpopulation of cells. Therapeutical interventions should target
      these cells rather than the tumour mass. Numerous studies have shown that the
      carbohydrate antigen structure CD176 (Thomsen-Friedenreich antigen, core-1) is
      present in many types of cancer and absent in normal adult human tissues. In this
      study, we assessed whether CD176 is co-expressed with CD44 or CD133 [markers of
      cancer-initiating cells (CIC)] in human lung, breast and liver carcinoma. A
      variety of human cancer cell lines and surgical specimens of these malignancies
      were examined. It was found that in most cases the majority of tumour cells
      stained strongly for CD44 by immunohistochemistry and flow cytometry, whereas
      CD133 expression was found on a smaller, but varying proportion of cells. Co
      expression of CD176 with CD44 was found at a surprisingly high percentage of
      cancer cells in vitro and in vivo. Co-expression of CD176 with CD133 was also
      detected, although at a lower rate. Tamoxifen treatment of MDA-435 breast cancer
      cells enhanced the CD44(+) /CD176(+) phenotype. Evidence is provided through a
      new sandwich solid-phase enzyme-linked immunosorbent assay (ELISA) suggesting
      that CD44 is a carrier molecule for CD176 not only in colorectal cancer as
      previously reported, but also in lung, breast and liver cancer. The expression of
      CD176 in CIC suggests that it may represent an effective target for tumour
      therapies.

PMID- 21070403
TI  - Molecular interactions of orthologues of floral homeotic proteins from the
      gymnosperm Gnetum gnemon provide a clue to the evolutionary origin of 'floral
      quartets'.
AB  - Several lines of evidence suggest that the identity of floral organs in
      angiosperms is specified by multimeric transcription factor complexes composed of
      MADS-domain proteins. These bind to specific cis-regulatory elements ('CArG
      boxes') of their target genes involving DNA-loop formation, thus constituting
      'floral quartets'. Gymnosperms, angiosperms' closest relatives, contain
      orthologues of floral homeotic genes, but when and how the interactions
      constituting floral quartets were established during evolution has remained
      unknown. We have comprehensively studied the dimerization and DNA-binding of
      several classes of MADS-domain proteins from the gymnosperm Gnetum gnemon.
      Determination of protein-protein and protein-DNA interactions by yeast two
      hybrid, in vitro pull-down and electrophoretic mobility shift assays revealed
      complex patterns of homo- and heterodimerization among orthologues of floral
      homeotic class B, class C and class E proteins and B(sister) proteins. Using
      DNase I footprint assays we demonstrate that both orthologues of class B with C
      proteins, and orthologues of class C proteins alone, but not orthologues of class
      B proteins alone can loop DNA in floral quartet-like complexes. This is in
      contrast to class B and class C proteins from angiosperms, which require other
      factors such as class E floral homeotic proteins to 'glue' them together in
      multimeric complexes. Our findings suggest that the evolutionary origin of floral
      quartet formation is based on the interaction of different DNA-bound homodimers,
      does not depend on class E proteins, and predates the origin of angiosperms.

PMID- 21070405
TI  - Metabolome and water homeostasis analysis of Thellungiella salsuginea suggests
      that dehydration tolerance is a key response to osmotic stress in this halophyte.
AB  - Thellungiella salsuginea, a Brassicaceae species closely related to Arabidopsis
      thaliana, is tolerant to high salinity. The two species were compared under
      conditions of osmotic stress to assess the relationships between stress
      tolerance, the metabolome, water homeostasis and growth performance. A broad
      range of metabolites were analysed by metabolic fingerprinting and profiling, and
      the results showed that, despite a few notable differences in raffinose and
      secondary metabolites, the same metabolic pathways were regulated by salt stress
      in both species. The main difference was quantitative: Thellungiella had much
      higher levels of most metabolites than Arabidopsis whatever the treatment.
      Comprehensive quantification of organic and mineral solutes showed a relative
      stability of the total solute content regardless of the species or treatment,
      meaning that little or no osmotic adjustment occurred under stress. The reduction
      in osmotic potential observed in plants under stress was found to result from a
      passive loss of water. Thellungiella shoots contain less water than Arabidopsis
      shoots, and have the ability to lose more water, which could contribute to
      maintain a water potential gradient between soil and plant. Significant
      differences between Thellungiella and Arabidopsis were also observed in terms of
      the physicochemical properties of their metabolomes, such as water solubility and
      polarity. On the whole, the Thellungiella metabolome appears to be more
      compatible with dehydration. Osmotic stress was also found to impact the
      metabolome properties in both species, increasing the overall polarity. Together,
      the results suggest that Thellungiella copes with osmotic stress by tolerating
      dehydration, with its metabolic configuration lending itself to osmoprotective
      strategies rather than osmo-adjustment.

PMID- 21070404
TI  - Two LysM receptor molecules, CEBiP and OsCERK1, cooperatively regulate chitin
      elicitor signaling in rice.
AB  - Chitin is a major molecular pattern for various fungi, and its fragments, chitin
      oligosaccharides, are known to induce various defense responses in plant cells. A
      plasma membrane glycoprotein, CEBiP (chitin elicitor binding protein) and a
      receptor kinase, CERK1 (chitin elicitor receptor kinase) (also known as LysM
      RLK1), were identified as critical components for chitin signaling in rice and
      Arabidopsis, respectively. However, it is not known whether each plant species
      requires both of these two types of molecules for chitin signaling, nor the
      relationships between these molecules in membrane signaling. We report here that
      rice cells require a LysM receptor-like kinase, OsCERK1, in addition to CEBiP,
      for chitin signaling. Knockdown of OsCERK1 resulted in marked suppression of the
      defense responses induced by chitin oligosaccharides, indicating that OsCERK1 is
      essential for chitin signaling in rice. The results of a yeast two-hybrid assay
      indicated that both CEBiP and OsCERK1 have the potential to form hetero- or homo
      oligomers. Immunoprecipitation using a membrane preparation from rice cells
      treated with chitin oligosaccharides suggested the ligand-induced formation of a
      receptor complex containing both CEBiP and OsCERK1. Blue native PAGE and chemical
      cross-linking experiments also suggested that a major portion of CEBiP exists as
      homo-oligomers even in the absence of chitin oligosaccharides.

PMID- 21070406
TI  - A central role for gamma-glutamyl hydrolases in plant folate homeostasis.
AB  - Most cellular folates carry a short poly-gamma-glutamate tail, and this tail is
      believed to affect their efficacy and stability. The tail can be removed by gamma
      glutamyl hydrolase (GGH; EC 3.4.19.9), a vacuolar enzyme whose role in folate
      homeostasis remains unclear. In order to probe the function of GGH, we modulated
      its level of expression and subcellular location in Arabidopsis plants and tomato
      fruit. Three-fold overexpression of GGH in vacuoles caused extensive
      deglutamylation of folate polyglutamates and lowered the total folate content by
      approximately 40% in Arabidopsis and tomato. No such effects were seen when GGH
      was overexpressed to a similar extent in the cytosol. Ablation of either of the
      major Arabidopsis GGH genes (AtGGH1 and AtGGH2) alone did not significantly
      affect folate status. However, a combination of ablation of one gene plus RNA
      interference (RNAi)-mediated suppression of the other (which lowered total GGH
      activity by 99%) increased total folate content by 34%. The excess folate
      accumulated as polyglutamate derivatives in the vacuole. Taken together, these
      results suggest a model in which: (i) folates continuously enter the vacuole as
      polyglutamates, accumulate there, are hydrolyzed by GGH, and exit as
      monoglutamates; and (ii) GGH consequently has an important influence on
      polyglutamyl tail length and hence on folate stability and cellular folate
      content.

PMID- 21070407
TI  - Functional analysis of folate polyglutamylation and its essential role in plant
      metabolism and development.
AB  - Cellular folates function as co-enzymes in one-carbon metabolism and are
      predominantly decorated with a polyglutamate tail that enhances co-enzyme
      affinity, subcellular compartmentation and stability. Polyglutamylation is
      catalysed by folylpolyglutamate synthetases (FPGSs) that are specified by three
      genes in Arabidopsis, FPGS1, 2 and 3, which reportedly encode plastidic,
      mitochondrial and cytosolic isoforms, respectively. A mutational approach was
      used to probe the functional importance of folate polyglutamylation in one-carbon
      metabolism and development. Biochemical analysis of single FPGS loss-of-function
      mutants established that folate polyglutamylation is essential for organellar and
      whole-plant folate homeostasis. However, polyglutamylated folates were still
      detectable, albeit at lower levels, in organelles isolated from the corresponding
      isozyme knockout lines, e.g. in plastids and mitochondria of the fpgs1
      (plastidial) and fpgs2 (mitochondrial) mutants. This result is surprising given
      the purported single-compartment targeting of each FPGS isozyme. These results
      indicate redundancy in compartmentalised FPGS activity, which in turn explains
      the lack of anticipated phenotypic defects for the single FPGS mutants. In
      agreement with this hypothesis, fpgs1 fpgs2 double mutants were embryo-lethal,
      fpgs2 fpgs3 mutants exhibited seedling lethality, and fpgs1 fpgs3 mutants were
      dwarfed with reduced fertility. These phenotypic, metabolic and genetic
      observations are consistent with targeting of one or more FPGS isozymes to
      multiple organelles. These data confirm the importance of polyglutamylation in
      folate compartmentation, folate homeostasis and folate-dependent metabolic
      processes, including photorespiration, methionine and pantothenate biosynthesis.

PMID- 21070408
TI  - Xrcc1-dependent and Ku-dependent DNA double-strand break repair kinetics in
      Arabidopsis plants.
AB  - Double-strand breakage (DSB) of DNA involves loss of information on the two
      strands of the DNA fibre and thus cannot be repaired by simple copying of the
      complementary strand which is possible with single-strand DNA damage. Homologous
      recombination (HR) can precisely repair DSB using another copy of the genome as
      template and non-homologous recombination (NHR) permits repair of DSB with little
      or no dependence on DNA sequence homology. In addition to the well-characterised
      Ku-dependent non-homologous end-joining (NHEJ) pathway, much recent attention has
      been focused on Ku-independent NHR. The complex interrelationships and regulation
      of NHR pathways remain poorly understood, even more so in the case of plants, and
      we present here an analysis of Ku-dependent and Ku-independent repair of DSB in
      Arabidopsis thaliana. We have characterised an Arabidopsis xrcc1 mutant and
      developed quantitative analysis of the kinetics of appearance and loss of gamma
      H2AX foci as a tool to measure DSB repair in dividing root tip cells of gamma
      irradiated plants in vivo. This approach has permitted determination of DSB
      repair kinetics in planta following a short pulse of gamma-irradiation,
      establishing the existence of a Ku-independent, Xrcc1-dependent DSB repair
      pathway. Furthermore, our data show a role for Ku80 during the first minutes post
      irradiation and that Xrcc1 also plays such a role, but only in the absence of Ku.
      The importance of Xrcc1 is, however, clearly visible at later times in the
      presence of Ku, showing that alternative end-joining plays an important role in
      DSB repair even in the presence of active NHEJ.

PMID- 21070410
TI  - Analysis of purified glabra3-shapeshifter trichomes reveals a role for NOECK in
      regulating early trichome morphogenic events.
AB  - Transcriptome analysis using the Affymetrix ATH1 platform has been completed on
      purified trichomes from the gl3-sst mutant. These trichomes display immature
      features, such as glassy cell walls and blunted branches. The gl3-sst trichome
      transcriptome was greatly enriched for genes involved in lipid biosynthesis,
      including those mediating the synthesis of fatty acids and wax. In addition, gl3
      sst trichomes displayed reduced expression of the R3 MYBs TRY and CPC, which
      normally function to limit trichome development. The expression of the MIXTA-like
      MYB gene NOK was elevated. Members of the MIXTA-like family promote conical cell
      outgrowth, and in some cases, trichome initiation in diverse plant species. In
      contrast, NOK limits trichome outgrowth in wild-type Arabidopsis plants. Similar
      to other MIXTA-like genes, NOK was required for the expansion of gl3-sst
      trichomes, as the gl3-sst nok double mutant trichomes were greatly reduced in
      size. Expression of NOK in nok mutants reduced branch formation, whereas in gl3
      sst nok, NOK expression promoted trichome cell outgrowth, illustrating duel roles
      for NOK in both promoting and limiting trichome development. MIXTA-like genes
      from phylogenetically diverse plant species could substitute for NOK in both nok
      and gl3-sst nok backgrounds. These findings suggest that certain aspects of NOK
      and MIXTA-like gene function have been conserved.

PMID- 21070409
TI  - PII is induced by WRINKLED1 and fine-tunes fatty acid composition in seeds of
      Arabidopsis thaliana.
AB  - The PII protein is an integrator of central metabolism and energy levels. In
      Arabidopsis, allosteric sensing of cellular energy and carbon levels alters the
      ability of PII to interact with target enzymes such as N-acetyl-l-glutamate
      kinase and heteromeric acetyl-coenzyme A carboxylase, thereby modulating the
      biological activity of these plastidial ATP- and carbon-consuming enzymes. A
      quantitative reverse transcriptase-polymerase chain reaction approach revealed a
      threefold induction of the AtGLB1 gene (At4g01900) encoding PII during early seed
      maturation. The activity of the AtGLB1 promoter was consistent with this pattern.
      A complementary set of molecular and genetic analyses showed that WRINKLED1, a
      transcription factor known to induce glycolytic and fatty acid biosynthetic genes
      at the onset of seed maturation, directly controls AtGLB1 expression. Immunoblot
      analyses and immunolocalization experiments using anti-PII antibodies established
      that PII protein levels faithfully reflected AtGLB1 mRNA accumulation. At the
      subcellular level, PII was observed in plastids of maturing embryos. To further
      investigate the function of PII in seeds, comprehensive functional analyses of
      two pII mutant alleles were carried out. A transient increase in fatty acid
      production was observed in mutant seeds at a time when PII protein content was
      found to be maximal in wild-type seeds. Moreover, minor though statistically
      significant modifications of the fatty acid composition were measured in pII
      seeds, which exhibited decreased amounts of modified (elongated, desaturated)
      fatty acid species. The results obtained outline a role for PII in the fine
      tuning of fatty acid biosynthesis and partitioning in seeds.

PMID- 21070411
TI  - Mutations in gamma-aminobutyric acid (GABA) transaminase genes in plants or
      Pseudomonas syringae reduce bacterial virulence.
AB  - Pseudomonas syringae pv. tomato DC3000 is a bacterial pathogen of Arabidopsis and
      tomato that grows in the apoplast. The non-protein amino acid gamma-amino butyric
      acid (GABA) is produced by Arabidopsis and tomato and is the most abundant amino
      acid in the apoplastic fluid of tomato. The DC3000 genome harbors three genes
      annotated as gabT GABA transaminases. A DC3000 mutant lacking all three gabT
      genes was constructed and found to be unable to utilize GABA as a sole carbon and
      nitrogen source. In complete minimal media supplemented with GABA, the mutant
      grew less well than wild-type DC3000 and showed strongly reduced expression of
      hrpL and avrPto, which encode an alternative sigma factor and effector,
      respectively, associated with the type III secretion system. The growth of the
      gabT triple mutant was weakly reduced in Arabidopsis ecotype Landberg erecta
      (Ler) and strongly reduced in the Ler pop2-1 GABA transaminase-deficient mutant
      that accumulates higher levels of GABA. Much of the ability to grow on GABA
      amended minimal media or in Arabidopsis pop2-1 leaves could be restored to the
      gabT triple mutant by expression in trans of just gabT2. The ability of DC3000 to
      elicit the hypersensitive response (HR) in tobacco leaves is dependent upon
      deployment of the type III secretion system, and the gabT triple mutant was less
      able than wild-type DC3000 to elicit this HR when bacteria were infiltrated along
      with GABA at levels of 1 mm or more. GABA may have multiple effects on P.
      syringae-plant interactions, with elevated levels increasing disease resistance.

PMID- 21070412
TI  - Characterization of the AE7 gene in Arabidopsis suggests that normal cell
      proliferation is essential for leaf polarity establishment.
AB  - The formation of leaf polarity is critical for leaf morphogenesis. In this study,
      we characterized and cloned an Arabidopsis gene, AS1/2 ENHANCER7 (AE7), which is
      required for both leaf adaxial-abaxial polarity formation and normal cell
      proliferation. The ae7 mutant exhibited leaf adaxial-abaxial polarity defects and
      double mutants combining ae7 with the leaf polarity mutants as1 (asymmetric
      leaves1), as2, rdr6 (RNA-dependent RNA polymerase6) or ago7/zip
      (argonaute7/zippy) all resulted in plants with an apparently enhanced loss of
      adaxial leaf identity. In addition, ae7 also showed decreased cell proliferation
      in both leaves and roots, compensated by increased cell sizes in leaves. AE7
      encodes a protein conserved in many eukaryotic organisms, ranging from
      unicellular yeasts to humans; however, the functions of AE7 family members from
      other species have not been reported. In situ hybridization revealed that AE7 is
      expressed in a spotted pattern in plant tissues, similar to cell-cycle marker
      genes such as HISTONE4. Moreover, the ae7 endoploidy and expression analysis of
      several cell-cycle marker genes in ae7 suggest that the AE7 gene is required for
      cell cycle progression. As the previously characterized 26S proteasome and
      ribosome mutants also affect both leaf adaxial-abaxial polarity and cell
      proliferation, similar to the defects in ae7, we propose that normal cell
      proliferation may be essential for leaf polarity establishment. Possible models
      for how cell proliferation influences leaf adaxial-abaxial polarity establishment
      are discussed.

PMID- 21070413
TI  - Perception of the chitin oligosaccharides contributes to disease resistance to
      blast fungus Magnaporthe oryzae in rice.
AB  - Chitin is a component of fungal cell walls, and its fragments act as elicitors in
      many plants. The plasma membrane glycoprotein CEBiP, which possesses LysM
      domains, is a receptor for the chitin elicitor (CE) in rice. Here, we report that
      the perception of CE by CEBiP contributes to disease resistance against the rice
      blast fungus, Magnaporthe oryzae, and that enhanced responses to CE by
      engineering CEBiP increase disease tolerance. Knockdown of CEBiP expression
      allowed increased spread of the infection hyphae. To enhance defense responses to
      CE, we constructed chimeric genes composed of CEBiP and Xa21, which mediate
      resistance to rice bacterial leaf blight. The expression of either CRXa1 or
      CRXa3, each of which contains the whole extracellular portion of CEBiP, the whole
      intracellular domain of XA21, and the transmembrane domain from either CEBiP or
      XA21, induced cell death accompanied by an increased production of reactive
      oxygen and nitrogen species after treatment with CE. Rice plants expressing the
      chimeric receptor exhibited necrotic lesions in response to CE and became more
      resistant to M. oryzae. Deletion of the first LysM domain in CRXA1 abolished
      these cellular responses. These results suggest that CEs are produced and
      recognized through the LysM domain of CEBiP during the interaction between rice
      and M. oryzae and imply that engineering pattern recognition receptors represents
      a new strategy for crop protection against fungal diseases.

PMID- 21070414
TI  - AtBBX21 and COP1 genetically interact in the regulation of shade avoidance.
AB  - Plants grown at high densities perceive the reduction in the ratio of red (R) to
      far-red (FR) light as a warning of competition. This light signal triggers
      morphological responses such as hypocotyl and stem elongation, and acceleration
      of flowering, which are known collectively as the shade-avoidance syndrome (SAS).
      Mutations in the photomorphogenic repressor COP1 suppress the SAS, but how COP1
      modulates these responses is uncertain. We identified a new mutant with altered
      responses to natural shade, named lhus (long hypocotyl under shade). lhus
      seedlings have longer hypocotyls than wild-type under a low R:FR ratio, but not
      under sunlight or darkness. The lhus phenotype is due to a mutation affecting a B
      box zinc finger transcription factor encoded by At1g75540, a gene previously
      reported as AtBBX21 that interacts with COP1 to control de-etiolation. Mutations
      in genes encoding other members of this protein family also result in impaired
      SAS regulation. Under short-term canopy shade, LHUS/BBX21 acts as positive
      regulator of SAS genes such as PAR1, HFR1, PIL1 and ATHB2. In contrast, global
      expression analysis of wild-type and lhus/bbx21 seedlings revealed that a large
      number of genes involved in hormonal signalling pathways are negatively regulated
      by LHUS/BBX21 in response to long-term canopy shade, and this observation fits
      well with the phenotype of lhus/bbx21 seedlings grown under a low R:FR ratio.
      Moreover, the bbx21 bbx22 double mutation restored the SAS in the cop1
      background. We propose that LHUS/BBX21 and other B-box-containing proteins, such
      as BBX22, act downstream of COP1, and play a central role in early and long-term
      adjustment of the SAS in natural environments.

PMID- 21070415
TI  - Biological origins of normal-chain hydrocarbons: a pathway model based on
      cuticular wax analyses of maize silks.
AB  - Long-chain normal hydrocarbons (e.g. alkanes, alkenes and dienes) are rare
      biological molecules and their biosynthetic origins are obscure. Detailed
      analyses of the surface lipids that accumulate on maize silks have revealed that
      these hydrocarbons constitute a large portion (>90%) of the cuticular waxes that
      coat this organ, which contrasts with the situation on maize seedling leaves,
      where the cuticular waxes are primary alcohols and aldehydes. The normal
      hydrocarbons that occur on silks are part of a homologous series of alkanes,
      alkenes and dienes of odd-number carbon atoms, ranging between 19 and 33 in
      number. The alkenes and dienes consist of a homologous series, each of which has
      double bonds situated at defined positions of the alkyl chains: alkenes have
      double bonds situated at the sixth, ninth or 12th positions, and dienes have
      double bonds situated at the sixth and ninth, or ninth and twelfth positions.
      Finding a homologous series of unsaturated aldehydes and fatty acids suggests
      that these alkenes and dienes are biosynthesized by a series of parallel pathways
      of fatty-acid elongation and desaturation reactions, which are followed by
      sequential reduction and decarbonylation. In addition, the silk cuticular waxes
      contain metabolically related unsaturated long-chain methylketones, which
      probably arise via a decarboxylation mechanism. Finally, metabolite profiling
      analyses of the cuticular waxes of two maize inbred lines (B73 and Mo17), and
      their genetic hybrids, have provided insights into the genetic control network of
      these biosynthetic pathways, and that the genetic regulation of these pathways
      display best-parent heterotic effects.

PMID- 21070416
TI  - ZmMYB31 directly represses maize lignin genes and redirects the phenylpropanoid
      metabolic flux.
AB  - Few regulators of phenylpropanoids have been identified in monocots having
      potential as biofuel crops. Here we demonstrate the role of the maize (Zea mays)
      R2R3-MYB factor ZmMYB31 in the control of the phenylpropanoid pathway. We
      determined its in vitro consensus DNA-binding sequence as ACC(T)/(A) ACC, and
      chromatin immunoprecipitation (ChIP) established that it interacts with two
      lignin gene promoters in vivo. To explore the potential of ZmMYB31 as a regulator
      of phenylpropanoids in other plants, its role in the regulation of the
      phenylpropanoid pathway was further investigated in Arabidopsis thaliana. ZmMYB31
      downregulates several genes involved in the synthesis of monolignols and
      transgenic plants are dwarf and show a significantly reduced lignin content with
      unaltered polymer composition. We demonstrate that these changes increase cell
      wall degradability of the transgenic plants. In addition, ZmMYB31 represses the
      synthesis of sinapoylmalate, resulting in plants that are more sensitive to UV
      irradiation, and induces several stress-related proteins. Our results suggest
      that, as an indirect effect of repression of lignin biosynthesis, transgenic
      plants redirect carbon flux towards the biosynthesis of anthocyanins. Thus,
      ZmMYB31 can be considered a good candidate for the manipulation of lignin
      biosynthesis in biotechnological applications.

PMID- 21070417
TI  - Cobtorin target analysis reveals that pectin functions in the deposition of
      cellulose microfibrils in parallel with cortical microtubules.
AB  - Cellulose and pectin are major components of primary cell walls in plants, and it
      is believed that their mechanical properties are important for cell
      morphogenesis. It has been hypothesized that cortical microtubules guide the
      movement of cellulose microfibril synthase in a direction parallel with the
      microtubules, but the mechanism by which this alignment occurs remains unclear.
      We have previously identified cobtorin as an inhibitor that perturbs the parallel
      relationship between cortical microtubules and nascent cellulose microfibrils. In
      this study, we searched for the protein target of cobtorin, and we found that
      overexpression of pectin methylesterase and polygalacturonase suppressed the
      cobtorin-induced cell-swelling phenotype. Furthermore, treatment with
      polygalacturonase restored the deposition of cellulose microfibrils in the
      direction parallel with cortical microtubules, and cobtorin perturbed the
      distribution of methylated pectin. These results suggest that control over the
      properties of pectin is important for the deposition of cellulose microfibrils
      and/or the maintenance of their orientation parallel with the cortical
      microtubules.

PMID- 21070418
TI  - LOST MERISTEMS genes regulate cell differentiation of central zone descendants in
      Arabidopsis shoot meristems.
AB  - Meristems of seed plants continuously produce new cells for incorporation into
      maturing tissues. A tightly controlled balance between cell proliferation in the
      center and cell differentiation at the periphery of the shoot meristem maintains
      its integrity. Here, we describe the role of three GRAS genes, named LOST
      MERISTEMS genes, in shoot apical meristem maintenance and axillary meristem
      formation. Under short photoperiods, the lom1 lom2 and lom1 lom2 lom3 mutants
      have arrested meristems characterized by an over-proliferation of meristematic
      cells and loss of polar organization. They also show early arrest of axillary
      meristem development and formation of ectopic meristematic cell clusters within
      the stem. LOM1 and LOM2 transcripts accumulate in the peripheral and basal zones
      of the SAM and in vascular strands. We show that LOM1 and LOM2 promote cell
      differentiation at the periphery of shoot meristems and help to maintain their
      polar organization.

PMID- 21070419
TI  - Cell wall composition contributes to the control of transpiration efficiency in
      Arabidopsis thaliana.
AB  - To identify loci in Arabidopsis involved in the control of transpirational water
      loss and transpiration efficiency (TE) we carried out an infrared thermal imaging
      based screen. We report the identification of a new allele of the Arabidopsis
      CesA7 cellulose synthase locus designated AtCesA7(irx3-5) involved in the control
      of TE. Leaves of the AtCesA7(irx3-5) mutant are warmer than the wild type (WT).
      This is due to reduced stomatal pore widths brought about by guard cells that are
      significantly smaller than the WT. The xylem of the AtCesA7(irx3-5) mutant is
      also partially collapsed, and we suggest that the small guard cells in the mutant
      result from decreased water supply to the developing leaf. We used carbon isotope
      discrimination to show that TE is increased in AtCesA7(irx3-5) when compared with
      the WT. Our work identifies a new class of genes that affects TE and raises the
      possibility that other genes involved in cell wall biosynthesis will have an
      impact on water use efficiency.

PMID- 21070420
TI  - Evolutionary trends in the floral transcriptome: insights from one of the
      basalmost angiosperms, the water lily Nuphar advena (Nymphaeaceae).
AB  - Current understanding of floral developmental genetics comes primarily from the
      core eudicot model Arabidopsis thaliana. Here, we explore the floral
      transcriptome of the basal angiosperm, Nuphar advena (water lily), for insights
      into the ancestral developmental program of flowers. We identify several thousand
      Nuphar genes with significantly upregulated floral expression, including homologs
      of the well-known ABCE floral regulators, deployed in broadly overlapping
      transcriptional programs across floral organ categories. Strong similarities in
      the expression profiles of different organ categories in Nuphar flowers are
      shared with the magnoliid Persea americana (avocado), in contrast to the largely
      organ-specific transcriptional cascades evident in Arabidopsis, supporting the
      inference that this is the ancestral condition in angiosperms. In contrast to
      most eudicots, floral organs are weakly differentiated in Nuphar and Persea, with
      staminodial intermediates between stamens and perianth in Nuphar, and between
      stamens and carpels in Persea. Consequently, the predominantly organ-specific
      transcriptional programs that characterize Arabidopsis flowers (and perhaps other
      eudicots) are derived, and correlate with a shift towards morphologically
      distinct floral organs, including differentiated sepals and petals, and a
      perianth distinct from stamens and carpels. Our findings suggest that the genetic
      regulation of more spatially discrete transcriptional programs underlies the
      evolution of floral morphology.

PMID- 21070421
TI  - Transcriptional silencing induced by Arabidopsis T-DNA mutants is associated with
      35S promoter siRNAs and requires genes involved in siRNA-mediated chromatin
      silencing.
AB  - The utility of many T-DNA insertion mutant lines of Arabidopsis is compromised by
      their propensity to trigger transcriptional silencing of transgenes expressed
      from the CaMV 35S promoter. To try to circumvent this problem, we characterized
      the genetic requirements for maintenance of 35S promoter homology-dependent
      transcriptional gene silencing induced by the dcl3-1 (SALK_005512) T-DNA
      insertion mutant line. Surprisingly, even though DCL3 and RDR2 are known
      components of the siRNA-dependent transcriptional gene silencing pathway,
      transcriptional gene silencing of a 35S promoter-driven GUS hairpin transgene did
      occur in plants homozygous for the dcl3-1 T-DNA insertion and was unaffected by
      loss of function of RDR2. However, the transcriptional gene silencing was
      alleviated in dcl2 dcl3 dcl4 triple mutant plants and also by mutations in AGO4,
      NRPD2, HEN1 and MOM1. Thus, some T-DNA insertion mutant lines induce 35S promoter
      homology-dependent transcriptional silencing that requires neither DCL3 nor RDR2,
      but involves other genes known to function in siRNA-dependent transcriptional
      silencing. Consistent with these results, we detected 35S promoter siRNAs in dcl3
      1 SALK line plants, suggesting that the 35S promoter homology-dependent silencing
      induced by some T-DNA insertion mutant lines is siRNA-mediated.

PMID- 21070422
TI  - A replication stress-induced synchronization method for Arabidopsis thaliana root
      meristems.
AB  - Synchronized cell cultures are an indispensable tool for the identification and
      understanding of key regulators of the cell cycle. Nevertheless, the use of cell
      cultures has its disadvantages, because it represents an artificial system that
      does not completely mimic the endogenous conditions that occur in organized
      meristems. Here, we present a new and easy method for Arabidopsis thaliana root
      tip synchronization by hydroxyurea treatment. A major advantage of the method is
      the possibility of investigating available Arabidopsis cell-cycle mutants without
      the need to generate cell cultures. As a proof of concept, the effects of over
      expression of a dominant negative allele of the B-type cyclin-dependent kinase
      CDKB1;1 gene on cell-cycle progression were tested. The previously observed
      prolonged G2 phase was confirmed, but was found to be compensated for by a
      reduced G1 phase. Furthermore, altered S-phase kinetics indicated a functional
      role for CDKB1;1 during the replication process.

PMID- 21070423
TI  - Influence of cryptic population structure on observed mating patterns in the wild
      progenitor of maize (Zea mays ssp. parviglumis).
AB  - Indirect two-generation analysis of pollen flow has proven to be an effective
      alternative to exhaustive paternity analysis in numerous plant populations. In
      this investigation, the method is extended to an annual wild maize species, Zea
      mays ssp. parviglumis (Poaceae). Our analysis of mating system in parviglumis
      revealed high levels of outcrossing and higher biparental inbreeding than
      typically observed in grasses. Pollen dispersal analysis suggested low levels of
      long-distance dispersal. Given previous evidence for intrapopulation genetic
      structure in parviglumis populations, we explored the impact of cryptic
      population structure on estimates of mating system and pollen flow.
      Subpopulations inferred through spatially explicit Bayesian assignment showed
      markedly different values for both mating system parameters and pollen flow than
      the entire population. Finally, a novel method of pollen haplotype assignment
      revealed nonrandom mating consistent with intrapopulation structure. These
      results indicate parviglumis could be particularly susceptible to habitat
      fragmentation currently occurring throughout Mexico due to recent changes in land
      use.

PMID- 21070424
TI  - Slow eye movement detection can prevent sleep-related accidents effectively in a
      simulated driving task.
AB  - A delayed response caused by sleepiness can result in severe car accidents.
      Previous studies suggest that slow eye movement (SEM) is a sleep-onset index
      related to delayed response. This study was undertaken to verify that SEM
      detection is effective for preventing sleep-related accidents. We propose a real
      time detection algorithm of SEM based on feature-extracted parameters of
      electrooculogram (EOG), i.e. amplitude and mean velocity of eye movement. In
      Experiment 1, 12 participants (33.5 +/- 7.3 years) performed an auditory
      detection task with EOG measurement to determine the threshold parameters of the
      proposed algorithm. Consequently, the valid threshold parameters were determined,
      respectively, as >5 degrees  and <30 degrees  s(-1) . In Experiment 2, 11
      participants (32.8 +/- 7.2 years) performed a simulated car-following task to
      verify that the SEM detection is effective for preventing sleep-related
      accidents. Accidents in the SEM condition were significantly more numerous than
      in the non-SEM condition (P < 0.01, one-way repeated-measures anova followed by
      Scheffe's test). Furthermore, no accident occurred in the SEM condition with a
      warning generated using the proposed algorithm. Results also demonstrate clearly
      that the SEM detection can prevent sleep-related accidents effectively in this
      simulated driving task.

PMID- 21070425
TI  - End-of-life care policies in Flemish residential care facilities accommodating
      persons with intellectual disabilities.
AB  - OBJECTIVE: This article aims to describe the presence, content and implementation
      strategies of written policies on end-of-life decisions in Flemish residential
      care facilities (RCFs) accommodating persons with intellectual disabilities (ID),
      and to describe training, education and quality assessments of end-of-life care.
      METHODS: A cross-sectional mail survey was conducted among general directors of
      all RCFs accommodating persons with ID (n = 140) in Flanders, Belgium.
      Institutions were asked to provide us with a copy of their end-of-life care
      policy documents for content analysis. RESULTS: Of the 140 institutions, 84 (60%)
      completed the questionnaire and 25 institutions provided 45 policy documents.
      Presence of policies on specific end-of-life decisions with a possible life
      shortening effect lay between 18% (palliative sedation) and 26% (withdrawing or
      withholding of life-prolonging treatment). The content analysis showed that the
      focus in the majority of these policy documents is on palliative care, while end
      of-life decisions with a possible life-shortening effect are mentioned but rarely
      elaborated on. Furthermore, few documents incorporate the distinctive features
      and needs of persons with ID regarding end-of-life care. On the other hand, half
      of the institutions trained and educated their professional care providers in
      some aspects of end-of-life care while one-third assessed the satisfaction of
      residents and families on several of these aspects. However, more than half
      reported explicitly that they have no plans for such assessments. CONCLUSIONS:
      The presence of end-of-life care policies is low in Flemish RCFs and their
      content is not very specific for persons with ID.

PMID- 21070426
TI  - Shear bond strength of denture teeth to heat- and light-polymerized denture base
      resin.
AB  - PURPOSE: To evaluate the shear bond strengths of highly cross-linked denture
      teeth bonded to heat-polymerized poly(methyl methacrylate) (PMMA) or a light
      polymerized urethane dimethacrylate (UDMA) denture base resin with or without a
      diatoric and with or without an acrylate bonding agent. MATERIALS AND METHODS:
      The denture base resins tested were Lucitone 199 (heat-polymerized PMMA) and
      Eclipse (light-polymerized UDMA). One hundred sixty mandibular central incisor
      denture teeth were divided into four groups (n = 40): group 1: ground surface as
      control; group 2: ground surface with diatoric; group 3: ground surface with
      bonding agent; group 4: ground surface with bonding agent and diatoric. Half of
      each group (n = 20) was processed with either heat- or light-polymerized resin.
      All specimens were treated with thermocycling for 1000 cycles, alternating
      between 5 and 55  degrees C with a dwell time of 30 seconds. Half the specimens
      in each group were treated with cyclic loading at 22 N for 14,400 cycles at 1.5
      Hz. All specimens were tested with shear load to failure. Data were analyzed with
      student's t-test, 2- and 3-way ANOVA, and Dunnett's T3 method (p < 0.05).
      RESULTS: Statistical analysis demonstrated no significant effect on shear bond
      strength from cyclic loading. For the Lucitone 199 (L) specimens, mean shear bond
      strengths and standard deviations were (N) 66.5 +/- 28.4, 72.7 +/- 31.5, 80.6 +/-
      17.1, and 76.9 +/- 21.9 for groups 1L, 2L, 3L, and 4L, respectively. For the
      Eclipse (E) specimens, mean shear bond strengths and standard deviations were (N)
      3.7 +/- 1.2, 7.3 +/- 3.3, 90.0 +/- 20.7, and 94.2 +/- 17.8 for groups 1E, 2E, 3E,
      and 4E, respectively. No statistically significant differences in shear bond
      strengths were noted for the Lucitone 199 groups (p = 0.11). Eclipse shear bond
      strengths were significantly higher in groups 3E and 4E than in groups 1E and 2E
      (p <= 0.05). In a 3-way ANOVA for groups 3 and 4, the shear bond strengths for
      the Eclipse specimens were significantly higher than the Lucitone 199 specimens
      (p = 0.01). CONCLUSIONS: When evaluating the shear bond strength of IPN denture
      teeth to denture base resins, specimens using an acrylate bonding agent with the
      Eclipse (light-polymerized) resin yielded significantly higher shear bond
      strengths than all of the Lucitone 199 groups and the Eclipse resin groups
      without a bonding agent.

PMID- 21070427
TI  - Immediate load on the edentulous mandible: treatment planning considerations.
AB  - Immediate load protocols for the edentulous mandible offer the patient many
      advantages in terms of decreased number of visits, improved early function, and
      reduction of surgical exposure; however, this treatment modality is not
      universally appropriate for all patients. The available evidence will assist the
      clinician in developing a customized and comprehensive informed consent. Patient
      selection and patient-mediated factors will dictate the suitability of not only a
      fixed or removable prosthesis, but also whether immediate loading would enhance
      the cost/benefit ratio. The indications, objective and subjective patient
      considerations, and design strategies are discussed for the immediate load
      scenario.

PMID- 21070428
TI  - The position of the occlusal plane in natural and artificial dentitions as
      related to other craniofacial planes.
AB  - PURPOSE: This study aimed at determining the most reliable ala-tragus line as a
      guide for the orientation of the occlusal plane in complete denture patients by
      use of cephalometric landmarks on dentate volunteers. MATERIALS AND METHODS:
      Analysis was made for prosthodontically related craniofacial reference lines and
      angles of lateral cephalometric radiographs taken for 47 dentate adults.
      Variables were determined and data were analyzed using SPSS (SPSS, Inc., Chicago,
      IL). RESULTS: Occlusal plane angle formed between the occlusal plane and Camper's
      plane had the lowest mean value in the angle formed with Camper's I, which
      represents the measure taken from the superior border of the tragus of the ear
      with a score of 2.1 degrees . The highest was measured in the angle formed with
      Camper's III with a score of 6.1 degrees , while the angle formed with Camper's
      II was 3.2 degrees . The differences between the three planes in relation to the
      occlusal plane was significant (p < 0.001). CONCLUSION: The superior border of
      the tragus with the inferior border of the ala of the nose was most accurate in
      orienting the occlusal plane.

PMID- 21070429
TI  - Foreign-trained dentists in advanced education in prosthodontics programs in the
      United States: demographics, perspectives on current training, and future goals.
AB  - PURPOSE: This study investigated the perspectives of foreign-trained dentists
      (FTDs) in comparison with US-trained Dentists (USTDs) in Advanced Education in
      Prosthodontics (AEP) programs on their current clinical training and future
      goals. MATERIALS AND METHODS: This study was conducted by analyzing data from
      previously published literature. When appropriate, Chi-square statistical
      analysis was conducted to determine the influence of where the AEP residents
      earned their DMD/DDS degree (FTDs/USTDs) on all variables. Only results that
      yielded significant differences were discussed. RESULTS: A majority of both FTDs
      and USTDs were male. Most USTDs were married, while most FTDs were single. Most
      FTDs were not US citizens and most originated from Asia, followed by the Middle
      East, South America, and Europe. Significantly more FTDs had higher ranks in
      their dental schools, had more advanced degrees, and spent more time practicing
      before entering the AEP programs. In selecting AEP programs, FTDs placed
      significantly higher values on a program's reputation and research opportunities.
      During their AEP training, FTDs paid significantly higher tuition and received
      lower stipends, but obtained more financial support from families. On the other
      hand, USTDs received significantly more financial aid and earned income from part
      time work, but had significantly higher total educational debts. USTDs showed a
      significantly higher interest in becoming a student member of the American
      College of Prosthodontists and participated actively in prosthodontics
      organizations. USTDs were more interested in becoming maxillofacial
      prosthodontists, while FTDs were more interested in pursuing academic careers.
      CONCLUSION: FTDs differed from USTDs in several ways. Because of their interests
      in academics and research, FTDs may potentially have a positive impact on the
      development of the prosthodontics discipline. This information may be beneficial
      for AEP program directors in accommodating the needs of FTDs, and for FTDs in
      better preparing for their AEP training.

PMID- 21070430
TI  - Prosthetic rehabilitation of a patient after surgical reconstruction of the
      maxilla: a clinical report.
AB  - Prosthetic management of maxillectomy cases is challenging, and a
      multidisciplinary approach is usually needed. This clinical report describes the
      treatment provided to a patient who presented with a moderately differentiated
      squamous cell carcinoma. A two-stage surgical protocol was followed for this
      purpose. At the first surgery, the anterior maxilla was resected, and the oral
      and nasal mucosal and osseous defect was reconstructed with an osteocutaneous
      flap from the radial forearm. At the second surgery, all fascias and the
      connective tissue between the skin and the bone were resected to provide an
      optimal thickness for denture stability. Two months after the second surgery,
      prosthetic rehabilitation was completed with a maxillary telescopic overdenture.
      During the 15-month follow-up period, the patient's oral condition and physical
      appearance improved, and no complications occurred.

PMID- 21070431
TI  - Immediate occlusal loading in edentulous jaws, CT-guided surgery and fixed
      provisional prosthesis: a maxillary arch clinical report.
AB  - Immediate occlusal loading (IOL) in edentulous jaws has been reported in numerous
      publications with implant cumulative survival rates consistent with conventional,
      unloaded healing protocols. Computed Tomography (CT)-guided surgery has more
      recently been developed and accepted as an additional treatment modality for
      maxillary and mandibular implant placement, with or without IOL. Reports as to
      the accuracy of planned versus actual implant placement in CT-guided surgeries
      have indicated that CT-guided surgery is not 100% accurate; standard deviations
      have been reported with values between 1 and 2 mm in terms of actual versus
      planned placement. The purpose of this article is to review the clinical
      parameters associated with IOL, and CT-guided surgery in edentulous jaws; and to
      present a clinical case illustrating the clinical and laboratory phases of
      treatment. The illustrated treatment was accomplished with an IOL protocol and
      includes fabrication and placement of a laboratory-processed provisional
      maxillary prosthesis. This particular protocol had slightly increased costs
      relative to conventional implant placement; however, the clinicians and patient
      benefited from improved accuracy of the provisional prostheses and decreased
      chairtime for the clinical procedures. The benefits and limitations of this
      treatment protocol are also discussed.

PMID- 21070432
TI  - Is it time to retire the term of "in situ carcinoma" and use the term of
      "borderline breast disease?".

PMID- 21070433
TI  - Clinical and radiologic data and core needle biopsy findings should dictate
      management of cellular fibroepithelial tumors of the breast.
AB  - Fibroepithelial lesions with cellular stroma identified on core needle biopsy
      (CNB) may prove to be either fibroadenoma or phyllodes tumor at excision;
      therefore, management of these rare lesions is highly controversial. We aim to
      assess the management and the outcome of 101 cellular fibroepithelial lesions
      diagnosed on CNB over a 6-year period in one institution. Consensus on clinical
      management in each individual patient was reached during multi-disciplinary
      conferences, based on careful correlation of clinical data with results of
      imaging studies and pathology of CNB samples. Radiologic findings (mammogram and
      sonogram) and multiple histologic parameters on CNB specimen were blindly re
      evaluated by one experienced breast radiologist and two breast pathologists,
      respectively, and results were correlated with final diagnosis at excision.
      Cellular fibroepithelial lesions with indeterminate or suspect imaging findings,
      with larger size, and with an equivocal comment such as "cannot rule out
      phyllodes tumor" in the pathology report were excised more frequently (p = 0.05,
      p = 0.034, and p = 0.01, respectively). Of 43 excised lesions, 13 were classified
      as benign phyllodes tumors, 23 as fibroadenoma and seven as benign cellular
      fibroepithelial lesion. The final diagnosis at excision did not significantly
      correlate with any clinical data, or with retrospective evaluation of imaging
      findings or comprehensive evaluation of multiple histologic parameters. In 58
      patients who had clinical and radiologic follow-up (mean +/- SD: 30 +/- 21
      months) there was no evidence of disease progression. No clinical and radiologic
      findings and/or comprehensive evaluation of multiple histologic parameters on CNB
      specimen are distinctive enough to predict final classification of equivocal
      cellular fibroepithelial lesions. However, careful clinico-pathologic and
      radiologic correlation may help to select the most clinically significant lesions
      for proper immediate surgical management. Follow-up alone may be an appropriate
      alternative for a subset of patients, given a good clinical, pathologic, and
      radiologic correlation.

PMID- 21070434
TI  - Preliminary Results in 173 Breast Cancer Patients Treated with Post-Lumpectomy
      MammoSite Single-Lumen Brachytherapy or Multi-Catheter Brachytherapy.
AB  - The objective of this study was to report our single-institution results with
      MammoSite and multi-catheter brachytherapy. Between February 2003 and January
      2009, 173 women with unifocal pathological Tis, T1, or T2 (up to 30 mm), N0 or N1
      carcinomas of the breast were treated with post-lumpectomy brachytherapy to 34 Gy
      in 10 fractions over 5-10 days. We treated 137 patients with MammoSite single
      lumen balloon brachytherapy, and 36 patients with multi-catheter brachytherapy.
      Patients with small and/or nonspherical lumpectomy cavities were usually treated
      with multi-catheter brachytherapy using 4-12 interstitial catheters. Median
      follow-up was 33 months. Three-year ipsilateral breast tumor control, disease
      free, and overall survival rates for MammoSite brachytherapy were 100%, 100%, and
      99%, respectively. Similar rates were obtained with multi-catheter brachytherapy.
      Minimum distances from the planning target volume for plan evaluation to a rib
      were 10 +/- 8 mm (mean +/- standard deviation) and 8 +/- 4 mm (mean +/- standard
      deviation) for MammoSite brachytherapy and multi-catheter brachytherapy,
      respectively (p = 0.48). Maximum rib doses were 101 +/- 14% (mean +/- standard
      deviation) and 74 +/- 10% (mean +/- standard deviation) of the prescribed dose
      for MammoSite brachytherapy and multi-catheter brachytherapy, respectively (p =
      0.001). Multi-catheter brachytherapy results in more conformal radiation dose
      delivery and a significantly lower rib dose than MammoSite single-lumen
      brachytherapy. Long-term follow-up is needed to determine if the delivery of a
      lower radiation dose to the ribs will translate into a lower incidence of rib
      pain and fractures.

PMID- 21070435
TI  - Measuring quality of life in oncologic breast surgery: a systematic review of
      patient-reported outcome measures.
AB  - Multiple randomized trials demonstrate equivalent survival between BCT and
      mastectomy, but clinical outcomes research must also evaluate patient
      satisfaction and quality of life. This review analyzes existing patient-reported
      outcome (PRO) measures in oncologic breast surgery to assess utility and make
      recommendations for future research. We performed a systematic literature review
      to identify PRO measures used in oncologic breast surgery patients. After
      applying inclusion and exclusion criteria, qualifying instruments were assessed
      for adherence to international guidelines for health outcomes instrument
      development and validation. Ten measures underwent development and psychometric
      evaluation in an oncologic breast surgery population. Five of ten measures (EORTC
      QLQ BR-23, FACT-B, HBIS, BIBCQ, and BREAST-Q) reported an adequate development
      and validation process. Three of these 5 measures (EORTC QLQ BR-23, FACT-B, HBIS)
      focused on non-surgical treatment issues. A fourth instrument (BIBCQ) did not
      address aesthetic concerns after breast reconstruction. The fifth instrument
      (BREAST-Q) was developed for use in patients undergoing mastectomy +/-
      reconstruction, but did not address breast-conserving therapy. Overall, two key
      limitations were noted: 1) surgery-specific issues of breast-conserving surgery
      patients were not well represented and 2) measures were largely developed without
      the aid of newer psychometric methods that may improve their clinical utility.
      Reliable and valid PRO measures in breast cancer patients exist, but even the
      best instruments do not address all important surgery-specific and psychometric
      issues of oncologic breast surgery patients. Newer psychometric methods would
      facilitate development of scales for use in individual patient care as well as
      group level comparisons.

PMID- 21070436
TI  - Effects of prior augmentation and reduction mammoplasty to sentinel node
      lymphatic mapping in breast cancer.
AB  - Previous plastic surgery procedures such as breast augmentation or reduction
      mammoplasty can potentially alter the lymphatic drainage of the breast. The
      purpose of this study is to determine the success rates of sentinel node
      lymphatic mapping in patients with previous plastic surgical procedures of the
      breast. A total of 83 patients with a history of plastic surgery of the breast
      that underwent subsequent sentinel node mapping between 1996 and 2008 were
      retrospectively analyzed. Eight-three patients that underwent a total of 108
      sentinel node biopsies. Hundred cases (93%) previously underwent breast
      augmentation and eight cases (7%) previously underwent reduction mammoplasty. The
      mean time between the previous plastic surgical procedures and the sentinel node
      biopsy was 10.3 years (range: 2 months-32 years). Indications for the mapping
      procedure were invasive cancer (n = 64), ductal carcinoma in situ (n = 17), and
      prophylactic mastectomy (n = 27). The identification rate of the sentinel node
      was 95.3% (103/108). The success rate based on type of procedure was 96% (96/100)
      for augmentation and 87.5% (7/8) for reduction mammoplasty. With a mean follow-up
      of 3.4 years, there has been only one local axillary recurrence that occurred at
      the time of an ipsilateral breast recurrence following lumpectomy. Lymphatic
      mapping can be successfully performed in patients who have previously undergone
      plastic surgery operations.

PMID- 21070437
TI  - The necrosis sign in magnetic resonance-mammography: diagnostic accuracy in 1,084
      histologically verified breast lesions.
AB  - Necrosis sign (NS) is a new descriptor for differential diagnosis of breast
      lesions in magnetic resonance (MR)-mammography (MRM). This study was designed:
      (a) to analyze diagnostic accuracy of NS in 1,084 histologically verified breast
      lesions, (b) to assess performance of NS in subgroups. This study was approved by
      the local ethical committee. All histologically verified lesions having undergone
      MR-mammography at our institution over 12 years were evaluated by experienced
      radiologists (> 500 MRM) according to standard protocols and study design (T1w;
      0.1 mmol/kg bw gadolinium diethylenetriamine penta-acetic acid; T2-turbo spin
      echo (TSE)). Patients with history of breast biopsy (surgically, minimal
      invasive), radiation- or chemotherapy <= 1 year before MRM were excluded. NS was
      assessed on T2w-TSE sequences and was rated positive if a hyperintense center in
      a hypointense lesion could be visualized (chi-squared test). One thousand and
      eighty-four lesions were available for statistical analysis (648: malignant, 436:
      benign). NS was significantly associated with malignancy (p < 0.001), providing
      specificity and positive predictive value (PPV) of 96.1% and 78.8%. Malignant
      lesions > 20 mm presented significantly more often NS (p < 0.001) than neoplasias
      <= 20 mm. There was no difference regarding prevalence of NS in small versus
      advanced benign lesions (n.s.), leading to better performance of NS in lesions >
      20 mm (PPV: 87.8%). Correlation between NS and Grading of invasive carcinomas was
      significant. In this study of 1,084 lesions necrosis sign was a specific and
      highly predictive feature for differential diagnosis in MRM (Specificity: 96.1%;
      PPV: 78.8%). This particularly counts for advanced lesions (PPV 87.8%). As this
      new descriptor correlates with Grading, it could be used as an initial estimate
      of patient's prognosis.

PMID- 21070439
TI  - Additional value of PET-CT in staging of clinical stage IIB and III breast
      cancer.
AB  - To evaluate retrospectively the accuracy of integrated PET/CT, against PET, CT,
      or conventional staging in breast cancer. Seventy consecutive biopsy proven
      clinical stage IIB and III breast cancer patients were included. Descriptive
      statistics of integrated PET/CT for the primary tumor, nodal status and
      metastasis detection were compared to PET, CT with contrast, and conventional
      staging (biochemistry, chest X-ray, liver ultrasound, and bone scintigraphy).
      Sensitivity of PET/CT for primary tumor and nodal status was 97.1% and 62.5%,
      respectively. Specificity and negative predictive value for nodal status were
      100% and 66.6%, respectively. The values for conventional staging for nodal
      involvement were 100% and 85.7% with a sensitivity of 87.5%. PET/CT showed
      metastatic disease in seven women despite normal conventional staging. PET/CT is
      able to visualize most clinical stage IIB and III primary breast cancers. PET/CT
      is superior to conventional staging for detecting internal mammary chain nodes
      and metastatic disease, but not for axillary staging. Future studies will have to
      test whether therapy adjustment based on PET/CT has the potential to improve
      survival.

PMID- 21070440
TI  - Bilateral breast carcinoma: clinical characteristics and its impact on survival.
AB  - The higher incidence of breast cancer, the improvements in diagnosis and
      treatment, together with the growing life expectancy have brought about an
      increase in the number of patients at risk for bilateral breast carcinoma. The
      aim of this study is to describe the characteristics of patients suffering from
      bilateral breast carcinoma who underwent surgery at the Breast Pathology Service
      of the Buenos Aires British Hospital and to analyze impact on survival. Between
      January 1970 and May 2007, 4,085 cases of breast carcinoma in 3,864 patients were
      treated at the Breast Diseases Division of the Buenos Aires British Hospital. A
      retrospective study of 194 patients with bilateral breast carcinoma was carried
      out: 80 synchronous and 114 metachronous. In order to compare survival, a group
      of 2,237 patients with unilateral breast carcinoma who had undergone surgery was
      analyzed. The risk of developing a contralateral breast carcinoma was 0.9% per
      year, with an accumulated risk at 15 years of 12.75%. The 5-year survival was
      85.9% for unilateral carcinomas, 94.6% for metachronous carcinoma, and 63.3% for
      synchronous carcinoma. The 15-year survival was 65.5% for unilateral carcinomas,
      52.3% for metachronous, and 37.2% for synchronous. The incidence of bilateral
      carcinomas is low. Survival was worse in patients with metachronous carcinoma
      diagnosed within 5 years of the first malignancy. Survival in patients with
      metachronous carcinoma diagnosed after 5 years is similar to those with
      unilateral carcinoma. Synchronous carcinoma was associated to worse survival,
      being an independent risk factor for mortality.

PMID- 21070438
TI  - High prevalence of low vitamin D and musculoskeletal complaints in women with
      breast cancer.
AB  - Reduced vitamin D levels may play a significant role in the development of
      fractures and musculoskeletal pains reported in patients on aromatase inhibitors
      (AIs) for breast cancer. In this study, we evaluated the vitamin D status in
      postmenopausal women with non-metastatic breast cancer who were about to start AI
      therapy. This study was conducted on community dwelling postmenopausal subjects,
      aged 35-80 years, with early non-metastatic breast cancer (up to stage IIIA), who
      were about to start therapy using third generation AIs. Symptoms of joint and
      muscle pains were obtained using a modified Leuven menopausal questionnaire. 25
      hydroxyvitamin D [25(OH)D] was evaluated by radioimmunoassay while bone mineral
      density (BMD) of the lumbar spine and the proximal femur by dual energy x-ray
      absorptiometry (DXA). Of the 145 participants (mean age = 60.96 +/- 0.88 years),
      63 of 145 (43.5%) had baseline levels of 25(OH)D of < 20 ng/mL (deficient), 50 of
      145 (34.5%) had levels between 20 and 29 ng/mL (insufficient), and only 32 of 145
      (22%) had >= 30 ng/mL (sufficient); thus, 113 of 145 (78%) had low 25(OH)D levels
      (i.e., < 30 ng/mL). Arthralgias and myalgias were found in 61.3% and 43% of
      patients, respectively; and of those, 83.3% and 88.1% had 25(OH)D of < 30 ng/mL,
      respectively. Prevalence of vitamin D deficiency is high in breast cancer women
      and this may increase the risk of bone loss and fractures in those who are going
      to start AIs. Moreover, musculoskeletal pains are common in breast cancer women,
      even before the initiation of AIs and in association with low vitamin D in the
      majority. Future studies may be needed to establish the contribution of low
      vitamin D, if any, on the prevalence of musculoskeletal pains in women on AIs.

PMID- 21070441
TI  - Complete response of brain metastases from breast cancer overexpressing Her-2/neu
      to radiation and concurrent Lapatinib and Capecitabine.
AB  - Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER
      2) have a predilection to metastasize to the brain. Therapeutic options for brain
      metastases with systemic therapy remain a challenge in those patients since
      targeted and chemotherapeutic agents have limited penetration through the blood
      brain barrier. Here we report the case of a patient with brain metastases from
      breast cancer overexpressing HER-2 who achieved a complete radiologic response
      after treatment by radiation and concurrent Lapatinib and Capecitabine.

PMID- 21070442
TI  - An unusual case of primary small cell neuroendocrine carcinoma of the breast.
AB  - Primary small cell neuroendocrine carcinoma of breast is a rare entity, with only
      case reports in literature. Histologically, these tumors are similar to small
      cell carcinoma of the lung with some evidence of ductal carcinoma-in-situ with
      areas of ductal, lobular, or papillary differentiation. Immunoreactivity for
      neuroendocrine markers is present in two thirds of cases, while 33-50% are
      positive for estrogen receptor or progesterone receptor. Her2/neu expression has
      not been reported in small cell carcinoma of the breast. Here we are presenting
      53-year-old women with locally advanced primary small cell neuroendocrine
      carcinoma of breast. We will discuss clinicopathological findings, treatment
      options, prognosis and review of the literature on primary small cell carcinoma
      of breast.

PMID- 21070443
TI  - Breast MRI for monitoring images of an "adenomyoepithelioma with malignant
      features", before, during, and after chemotherapy.

PMID- 21070444
TI  - Multi-centric breast cancer involving a ventriculoperitoneal shunt.

PMID- 21070445
TI  - Bilateral primary breast Burkitt's lymphoma.

PMID- 21070446
TI  - Primary osteosarcoma of the breast.

PMID- 21070447
TI  - Breast sporotrichosis.

PMID- 21070448
TI  - Early reduction in standardized uptake value after one cycle of neoadjuvant
      chemotherapy measured by sequential FDG PET/CT is an independent predictor of
      pathological response of primary breast cancer.

PMID- 21070449
TI  - A case of metaplastic carcinoma of the breast responsive to chemotherapy with
      Ifosfamide and Etoposide: improved antitumor response by targeting sarcomatous
      features.

PMID- 21070450
TI  - Disparities in breast cancer in Puerto Rico and among Hispanics, non-Hispanic
      whites, and non-Hispanics blacks in the United States, 1992-2004.

PMID- 21070451
TI  - Prognosis of microinvasive breast carcinoma with negative axillary nodes in
      accordance with TNM classification criteria.

PMID- 21070452
TI  - Outcome of elderly breast cancer patients in china: the influence of prognostic
      factors and adjuvant systemic therapies.

PMID- 21070453
TI  - Prognostic factors in patients with breast cancer and malignant pleural effusion.

PMID- 21070454
TI  - Introduction to 2010 special issue on botulinum toxins.

PMID- 21070456
TI  - A double-blind, randomized, placebo-controlled health-outcomes survey of the
      effect of botulinum toxin type a injections on quality of life and self-esteem.
AB  - BACKGROUND: Although studies show that botulinum toxin type A (BoNTA) can
      positively influence one's first impression, little research has been conducted
      to measure the effect that BoNTA has on mental well-being. OBJECTIVE: To
      determine the effects that BoNTA injections for the treatment of facial wrinkles
      had on quality of life (QOL) and self-esteem. METHODS AND MATERIALS: One hundred
      participants received treatment with BoNTA or placebo saline in this double-blind
      randomized placebo-controlled survey. All participants completed a health
      outcomes survey consisting of Quality of Life Enjoyment and Satisfaction
      Questionnaire-Short Form and Heatherton and Polivy State Self-Esteem measurements
      before injection and 2 weeks and 3 months after injection. RESULTS: Statistically
      significant improvements (p<.05) in participants treated with BoNTA were observed
      in answers to QOL questions regarding physical health, mood, household
      activities, overall life satisfaction, body satisfaction, self-consciousness,
      intellect, self-worth, appearance, comprehension, weight satisfaction,
      attractiveness, and sense of well-being. Increases in overall self-esteem and
      appearance-, social-, and performance-related self-esteem were observed in
      participants treated with BoNTA. CONCLUSION: Our findings showed that BoNTA
      injections result in improvements in QOL and self-esteem. In addition, BoNTA
      naive participants demonstrate greater improvements in QOL and self-esteem than
      participants previously exposed to BoNTA. Moreover, BoNTA-familiar participants
      demonstrated sustained improvement in QOL and self-esteem relative to BoNTA-naive
      participants, even when injected with placebo.

PMID- 21070458
TI  - A randomized, controlled, double-blind study of light emitting diode
      photomodulation for the prevention of radiation dermatitis in patients with
      breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Radiation dermatitis occurs in a majority of patients
      with breast cancer who receive radiation therapy (RT), causes significant pain,
      and may necessitate treatment delay. Light emitting diode (LED) photomodulation
      has been reported to minimize radiation dermatitis. This study sought to further
      evaluate the efficacy of LED photomodulation in lessening radiation dermatitis.
      MATERIALS & METHODS: After surgery, patients with breast cancer received LED
      photomodulation or sham treatments in conjunction with three-dimensional
      conformal RT. Reactions were evaluated using standardized photographs graded
      according to National Cancer Institute criteria. RESULTS: In the LED treatment
      group (n=18), no patients had grade 0 reactions, six (33.3%) had grade 1
      reactions, 12 (66.7%) had grade 2 reactions, and none had a grade 3 reaction. In
      the sham treatment group (n=15), one (6.6%) patient had a grade 0 reaction, four
      (26.7%) had grade 1 reactions, 9 (60.0%) had grade 2 reactions, and one (6.7%)
      had a grade 3 reaction. Two (11.1%) patients in the LED treatment group and one
      (6.7%) in the control group had to interrupt treatment. Differences between
      groups were not statistically significant. CONCLUSION: LED photomodulation did
      not reduce the incidence of radiation-induced skin reactions or interruptions in
      therapy. .

PMID- 21070457
TI  - Multicenter, randomized, parallel-group study of onabotulinumtoxinA and
      hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in
      combination for lower facial rejuvenation: satisfaction and patient-reported
      outcomes.
AB  - BACKGROUND: Patient-reported outcomes (PROs) are important assessment benchmarks
      after aesthetic procedures. Systematic studies of PROs have not been conducted in
      the lower face. OBJECTIVE: To study satisfaction and other PROs after treatment
      of the lower face with onabotulinumtoxinA and a 24-mg/mL smooth, cohesive
      hyaluronic acid (HA) gel filler, alone or in combination. METHODS: Ninety female
      participants aged 35 to 55 were randomized to one of three groups: 24-mg/mL
      cohesive gel alone (n=30), onabotulinumtoxinA alone (n=30), or the combination
      (n=30). Effectiveness outcomes were investigator- and participant-rated
      satisfaction and the participant Self-Perception of Age (SPA) and participant
      rated Look and Feel of the Lips and Mouth (LAF) questionnaires. Participants
      maintained a 14-day diary to record severity of treatment site responses.
      RESULTS: All treatments resulted in significant improvements from baseline at all
      end points and on all PRO measures. For all measures and most time points, the 24
      mg/mL cohesive gel treatment groups experienced greater improvements than
      onabotulinumtoxinA alone. Participant-rated severity of treatment-related
      reactions was mainly mild and transient. CONCLUSION: OnabotulinumtoxinA and 24
      mg/mL cohesive HA gel treatments, used alone or in combination for lower face
      rejuvenation, resulted in significant improvement in investigator- and
      participant-reported outcomes.

PMID- 21070459
TI  - Lower-fluence, higher-density versus higher-fluence, lower-density treatment with
      a 10,600-nm carbon dioxide fractional laser system: a split-face, evaluator
      blinded study.
AB  - BACKGROUND: Adequate laser settings in the treatment of scars using a carbon
      dioxide fractional laser system (CO(2) FS) have not been established. OBJECTIVE:
      To compare the efficacy and safety of low-fluence, high-density with high
      fluence, low-density treatment with CO(2) FS on acne scars and enlarged pores.
      METHODS: Ten patients with mild to severe atrophic acne scars and enlarged pores
      were enrolled. Half of each subject's face was treated with a single session of
      CO(2) FS with a fluence of 70 mJ and a density of 150 spots/cm(2) ; the other
      half was treated with a fluence of 30 mJ and a density of 250 spots/cm(2) .
      RESULTS: Follow-up results 3 months after a single low-fluence, high-density
      treatment with CO(2) FS showed that four of 10 participants had clinical
      improvement of 51% to 75% from baseline. After the high-fluence, low-density
      CO(2) FS treatment, five of 10 patients demonstrated marked clinical improvements
      of more than 76%. CONCLUSION: Higher-energy, lower-density laser settings seem to
      be more effective than lower-energy, higher-density settings for acne scars and
      enlarged pores, although our results do not constitute a conclusive comparison of
      the two different modes of CO(2) FS.

PMID- 21070460
TI  - Liquid nitrogen: temperature control in the treatment of actinic keratosis.
AB  - BACKGROUND: Actinic keratoses (AKs) are in situ epidermal tumors that may
      progress to invasive squamous cell carcinomas. Liquid nitrogen is used during
      cryotherapy to freeze the epidermis and upper dermis and is the standard
      treatment for individual AKs. OBJECTIVE: To evaluate the efficacy of a
      cryosurgery device incorporating an infrared sensor to measure the temperature at
      the skin surface while spraying liquid nitrogen on the surface of the skin during
      the treatment of AKs. METHODS & MATERIALS: Thirty-six patients with 180 thin AKs
      were treated with liquid nitrogen spray to a temperature of -5 degrees C using
      the sensor to control the temperature at the skin surface. Patients were
      evaluated for cure rate, side effects, and healing time. RESULTS: At the 1-week
      follow-up, 66.7% of the lesions were cleared. By the 6-week follow-up, there was
      a 100% cure rate. Side effects were limited to redness, blistering, crusting,
      oozing, and ulceration at the 1-week follow-up and were resolved by the 6-week
      follow-up. No recurrence of AK, scarring, or hypopigmentation was noted.
      CONCLUSION: Cryotherapy with an integrated sensor for temperature control is an
      effective, safe, and precise treatment, allowing for a 100% short-term cure rate
      of AKs.

PMID- 21070461
TI  - Assessing the public's preference for surgical treatment of primary basal cell
      carcinoma: a discrete-choice experiment in the south of the Netherlands.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is a slowly growing nonmelanoma type of
      skin cancer that often is located on the face. Different therapies are available
      to treat BCC, of which surgical excision (SE) and Mohs micrographic surgery (MMS)
      are the most frequently used surgical procedures. OBJECTIVES: To examine which
      attributes of a surgical treatment the general public values as important and to
      determine the incremental willingness to pay for MMS versus SE. METHODS: A
      discrete-choice experiment (DCE) was conducted among members of the general
      public to examine which attributes of a surgical treatment for primary BCC are
      valued as important. In addition, based on the attributes included in the
      experiment, the willingness to pay for MMS versus SE was determined. RESULTS:
      Respondents (N=312) preferred a treatment with a lower recurrence rate, shorter
      surgery time, shorter travelling time, shorter waiting time, no risk for re
      excision, and lower cost. The incremental willingness to pay for MMS was 847 euro
      ($1,203). CONCLUSIONS: Results from this DCE indicate that, when outcome and
      process attributes are considered from a societal perspective, MMS is preferred
      over SE for primary BCC. The authors have indicated no significant interest with
      commercial supporters.

PMID- 21070462
TI  - Repair of scalp defects using an H-plasty type of bilateral advancement flap.
AB  - BACKGROUND: Defects of the scalp often pose a reconstructive challenge in
      dermatologic surgery. OBJECTIVE We report our experience with the H-plasty type
      of bilateral advancement flap for the closure of small to medium-sized scalp
      defects that cannot be closed primarily. METHODS: In this case series study, 69
      scalp defects 1.5 to 3.0 cm in diameter that could not be closed primarily were
      repaired using the H-plasty type of bilateral advancement flap. RESULTS: Sixty
      nine 1.5- to 3.0-cm-diameter scalp defects resulting from Mohs micrographic
      surgery that could not be closed primarily were identified over the 2-year study
      period. All 69 defects were closed entirely with the bilateral advancement flap,
      and there were no significant complications. CONCLUSIONS; The H-plasty type of
      bilateral advancement flap allows appropriately selected scalp defects that might
      not be readily closed primarily to be repaired easily using local skin, providing
      an attractive alternative to other flap techniques, skin grafting, and healing
      via secondary intention. The limitations of this study are that the results are
      based on a retrospective single-surgeon experience and that there was no long
      term follow-up scheduled to evaluate the final cosmetic outcome of the repair.

PMID- 21070463
TI  - Assessment and management of chemical exposure in the Mohs laboratory.
AB  - BACKGROUND: The correct handling, storage, and disposal of chemicals used in the
      processing of tissue for Mohs micrographic surgery are essential. OBJECTIVES: To
      identify the chemicals involved in the preparation of Mohs frozen sections and
      assess the associated occupational health risks. To quantify exposure levels of
      hazardous chemicals and ensure that they are minimized. METHODS: A risk
      assessment form was completed for each chemical. Atmospheric sampling was
      performed at our previous laboratory for formaldehyde and volatile organic
      compounds. These data were used in the design of our new facility, where testing
      was repeated. RESULTS: Twenty-five chemicals were identified. Ten were classified
      as hazardous substances, 10 were flammable, six had specific disposal
      requirements, four were potential carcinogens, and three were potential
      teratogens. Formaldehyde readings at our previous laboratory were up to eight
      times the national exposure standard. Testing at the new laboratory produced
      levels well below the exposure standards. CONCLUSION: Chemical exposure within
      the Mohs laboratory can present a significant occupational hazard. Acutely toxic
      and potentially carcinogenic formaldehyde was found at high levels in a
      relatively standard laboratory configuration. A laboratory can be designed with a
      combination of physical environment and operational protocols that minimizes
      hazards and creates a safe working environment.

PMID- 21070465
TI  - Morphometric analysis of the human scalp hair follicle: practical implications
      for the hair transplant surgeon and hair regeneration studies.
AB  - BACKGROUND: The bulge stem cell region is a structure important for the
      regeneration of the pilosebaceous unit. Measurements of the different
      compartments of a hair follicle may have implications in hair transplantation and
      hair regeneration studies. OBJECTIVE: To measure the length of the different
      portions of the occipital scalp hair and to estimate at what depth they are
      located. METHODS AND MATERIAL: Hair follicles from the occipital scalp were
      obtained from 29 individuals. Measurements were performed on digital pictures
      using a software imaging system. Antibody anticytokeratin (CK), 15 was used as a
      bulge stem cell marker. RESULTS: The mean length of a scalp hair follicle is 4.16
      mm. The infundibulum measures 0.76 mm, the isthmus 0.89 mm, and the inferior
      portion 2.5 mm. The insertion of the arrector pili muscle is located 1.65 mm
      deep. CK15 immunoreactivity starts at a depth of 1 mm and extends down to 1.8 mm.
      CONCLUSION: The ideal depth for the trichophytic procedure is to cut the wound
      edge at a depth of less than 1 mm to avoid the bulge zone. The data provided can
      serve as an objective anatomical reference in hair regeneration studies using
      horizontally transected follicles.

PMID- 21070464
TI  - Optical transfer diagnosis of pigmented lesions.
AB  - BACKGROUND: Optical transfer diagnosis is a novel melanoma detection system that
      uses morphologic-physiologic mapping. OBJECTIVE: To further evaluate the
      potential of optical transfer diagnosis for distinguishing benign from malignant
      pigmented melanocytic neoplasms. METHODS AND MATERIALS: Ninety-four patients with
      pigmented lesions suggestive of melanoma were referred for optical transfer
      diagnosis. After lesions were scanned with the camera, they were removed for
      histopathologic examination by two dermatopathologists each. From the recorded
      images, morphologic-physiologic maps were created with prediction models of light
      absorption and scattering by chromophores such as hemoglobin, keratin, and
      melanin at different epidermal and dermal depths. Entropy and relative entropy
      values derived from the morphologic-physiologic maps and a set of pure
      morphologic parameters were analyzed for output prediction of melanoma versus
      nonmelanoma. Dermoscopic images were reviewed and scored using the color,
      architecture, symmetry, and homogeneity (CASH) algorithm to assign a value of
      clinical atypia. RESULTS Of the 118 scanned and biopsied lesions (median CASH
      score 8), 11 were identified as melanoma or atypical melanocytic hyperplasia
      consistent with melanoma. For identification of melanomas, optical transfer
      diagnosis had a sensitivity of 100% and a specificity of 90%. CONCLUSIONS: This
      technology continues to be a promising adjunct to clinical skin cancer screening.

PMID- 21070466
TI  - A new surgical technique for the correction of pincer-nail deformity: combination
      of splint and nail bed cutting.
AB  - BACKGROUND: Pincer nail is a kind of nail deformity characterized by a transverse
      overcurvature of the nail that increases along the longitudinal axis. Many
      conservative and surgical treatment modalities have been reported. PURPOSE:
      Widening the nail bed and use of aspiration tube splint in pincer nail surgery.
      MATERIALS AND METHODS: Pincer nail was treated by surgery with splinting in 11
      patients. In this procedure, the nail bed is enlarged in a transverse direction
      using incisions on the nail bed. RESULTS The postoperative follow-up ranged from
      12 to 19 months (mean 15 months). Excellent results were obtained in all
      patients. No further complications were reported. CONCLUSIONS: The splint can
      prevent contracture of the nail matrix and nail bed. Widening and flattening the
      nail bed using an aspiration tube splint provided a longstanding effective
      treatment of pincer nail deformity and pain relief. The authors have indicated no
      significant interest with commercial supporters.

PMID- 21070467
TI  - Complications after treatment with polyalkylimide.

PMID- 21070468
TI  - Inadvertent arterial injection using catheter-assisted sclerotherapy resulting in
      amputation.

PMID- 21070469
TI  - The vascular system of the superior auricular artery: anatomical study and
      clinical application.
AB  - BACKGROUND: The retroauricular flap has many advantages for facial
      reconstruction, but it is difficult to perform reconstruction of the upper part
      of the auricle and its surroundings. METHODS: We investigated the relationship
      between the superior auricular artery and its surrounding structures through
      anatomic studies with seven fresh cadavers and applied the findings clinically.
      From February 2008 to December 2009, we performed 12 cases with the superior
      auricular artery island flap to reconstruct defects in the upper region of the
      auricle and its surroundings. RESULTS: We found that the superior auricular
      artery is a reliable pedicle for the retroauricular flap. All wounds of the
      patients were successfully closed, with the exception of one minor complication.
      The aesthetic outcomes of the donor and recipient sites were satisfactory.
      CONCLUSIONS: The superior auricular artery island flap has several advantages.
      Therefore, we suggest that the superior auricular artery island flap can be
      another choice for reconstructing soft tissue defects at the upper region of the
      auricle and its surrounding area.

PMID- 21070470
TI  - Standardized photography in facial reconstructive surgery: clinical pearls to
      simplify a complicated task.

PMID- 21070471
TI  - Electrocautery and computerized bipolar coagulation simplify nail surgery.

PMID- 21070472
TI  - Complication of CROSS-technique on boxcar acne scars: atrophy.

PMID- 21070473
TI  - The successful treatment of Schamberg's disease with the 595 nm vascular laser.

PMID- 21070474
TI  - Granuloma Faciale treated with 595-nm pulsed dye laser.

PMID- 21070475
TI  - Positron emission tomography imaging and biodistribution of vascular endothelial
      growth factor with 64Cu-labeled bevacizumab in colorectal cancer xenografts.
AB  - Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic
      factor responsible for the development of tumor vasculature. The aim of this
      study was to image VEGF expression with (64)Cu-labeled anti-VEGF antibody
      (bevacizumab) non-invasively, and to see whether or not the expression was
      correlated with tumor accumulation in colorectal cancer xenografts. Bevacizumab
      was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane
      1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with (64)Cu. In vivo
      biodistribution studies and positron emission tomography (PET) imaging were
      performed on mice bearing human colorectal cancer (HT29) xenografts after
      injection of (64)Cu-DOTA-bevacizumab, which showed clear accumulation of (64)Cu
      DOTA-bevacizumab in the tumor (22.7 +/- 1.0 %ID/g, 24 +/- 0.2 %ID/g, 19.0 +/- 2.5
      %ID/g at 24, 48 and 72 h, respectively). Tumor accumulation of (64)Cu-DOTA
      bevacizumab was significantly correlated with VEGF expression as measured by
      western blot (rho = 0.81, P = 0.004). Vascular endothelial growth factor blocking
      with unlabeled bevacizumab significantly reduced tumor accumulation of (64) Cu
      DOTA- bevacizumab (9.7 +/- 1.2 %ID/g, P < 0.001) at 48 h. Interestingly, the
      blood concentration of VEGF in the mice treated with excess fold of bevacizumab
      was significantly higher than those without at 48 h (25.5 +/- 4.6 %ID/g vs 6.5 +/
      2.1 %ID/g, P = 0.0016). Liver uptake decreased from 24 h (17.2 +/- 1.7 %ID/g) to
      48 h (13.0 +/- 4.2 %ID/g) and 72 h (10.6 +/- 1.5 %ID/g) due to hepatic clearance
      of the tracer. The present study successfully showed (64) Cu-DOTA-bevacizumab as
      a potential PET tracer for non-invasive imaging of VEGF expression in colorectal
      cancer xenografts.

PMID- 21070476
TI  - Upregulation of delta-catenin is associated with poor prognosis and enhances
      transcriptional activity through Kaiso in non-small-cell lung cancer.
AB  - delta-Catenin is the only member of the p120 catenin (p120ctn) subfamily that its
      primary expression is restricted to the brain. Since delta-catenin is upregulated
      in human lung cancer, the effects of delta-catenin overexpression in lung cancer
      still need to be clarified. Immunohistochemistry was performed to investigate the
      expression of delta-catenin and Kaiso, a delta-catenin-binding transcription
      factor, in 151 lung cancer specimens. A correlation between cytoplasmic delta
      catenin and Kaiso expression was also associated with high TNM stage, lymph node
      metastases and poor prognosis. Co-immunoprecipitation assay confirmed the
      interactions of delta-catenin and Kaiso in lung cancer cells. In addition, gene
      transfection and RNAi technology were used to demonstrate that increased delta
      catenin expression was promoted, whereas its knockdown suppressed its lung cancer
      invasive ability. In addition, methylation-specific PCR and ChIP assay
      demonstrated that delta-catenin could regulate MTA2 via Kaiso in a methylation
      dependent manner, while it could regulate cyclin D1 and MMP7 expression through
      Kaiso in a sequence-specific manner. In conclusion, a delta-catenin/Kaiso pathway
      exists in lung cancer cells. Increased delta-catenin expression is critical for
      maintenance of the malignant phenotype of lung cancer, making delta-catenin a
      candidate target protein for future cancer therapeutics.

PMID- 21070477
TI  - Unique p53 and epidermal growth factor receptor gene mutation status in 46
      pulmonary lymphoepithelioma-like carcinomas.
AB  - p53 and epidermal growth factor receptor (EGFR) are common genes involved in the
      pathogenesis of lung cancer, but their roles in lymphoepithelioma-like carcinomas
      (LELC) are unclear. In this study, we investigate the roles of p53 and EGFR in
      LELC carcinogenesis. Forty-six pulmonary LELCs were identified to evaluate p53
      and EGFR aberrations. p53 mutations were identified in three patients, which all
      occurred in exon 8. EGFR mutations were detected in 8 of 46 cases with a majority
      of exon 21 mutations but without L858R. The other cases harbored mutations in
      exons 20 and 18. Only one case gained a deletion in exon 19. Notably, EGFR
      mutation was more commonly observed in patients with tumor size <= 3 cm (P =
      0.014). In addition, there was a trend of more common EGFR overexpression in
      female (22/30) than in male patients (7/16, P = 0.061). However, there was no
      correlation between p53/EGFR mutations and protein expressions, suggesting the
      presence of complex mechanisms. p53 and EGFR mutations are uncommon in LELCs,
      indicating that these genes are not the important events in carcinogenesis for
      this tumor subtype. The EGFR mutation in 35% patients with LELC tumors <3 cm in
      size suggests the potential benefits to EGFR tyrosine kinase inhibitors of
      inoperable LELCs.

PMID- 21070478
TI  - Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called
      well-differentiated tumor of uncertain malignant potential: a morphological,
      immunohistochemical, and molecular appraisal.
AB  - There is a continuous debate regarding the classification of thyroid follicular
      lesions and the term "well-differentiated tumor of uncertain malignant potential
      (WDT-UMP)" was recently introduced to cover this problematic spectrum of tumors.
      The objective of this study was to reappraise WDT-UMP using morphological,
      immunochemical, and molecular analysis and to shed more light on encapsulated
      thyroid follicular-patterned tumors. A total of 30 cases of WDT-UMP with
      equivocal papillary thyroid carcinoma-type nuclear changes (PTC-N) or focal
      unequivocal PTC-N were examined. As a control, follicular adenoma (n = 29),
      follicular carcinoma (n = 8), hyalinizing trabecular adenoma (n = 5), and PTC (n
      = 48) were included. HBME-1, cytokeratin 19, and galectin-3 were positive in 12
      (40.0%), 10 (33.3%) and 11 (36.7%) cases of WDT-UMP, respectively. According to
      the positivity of those markers, significant differences were obtained between
      WDT-UMP and PTC encapsulated common type (P = 0.028, 0.010, and 0.004,
      respectively), infiltrative follicular variant (P = 0.020, 0.026, and 0.008,
      respectively), and infiltrative common type (P = 0.004, 0.001, and 0.005,
      respectively), but not between WDT-UMP and follicular adenoma or follicular
      carcinoma. BRAF(V600E) mutation was absent but RET/PTC1 rearrangement was found
      in only two (6.7%) cases of WDT-UMP. None of the 20 patients with WDT-UMP
      developed recurrence, with an average follow-up of 80 months. These findings
      indicate that WDT-UMP has a favorable outcome and is distinct from PTC in
      morphological, immunohistochemical, and molecular characteristics. We propose
      that WDT-UMP should be classified as "well-differentiated tumor with uncertain
      behavior".

PMID- 21070479
TI  - Fermented and non-fermented soy food consumption and gastric cancer in Japanese
      and Korean populations: a meta-analysis of observational studies.
AB  - Soy food is known to contribute greatly to a reduction in the risk of gastric
      cancer (GC). However, both Japanese and Korean populations have high incidence
      rates of GC despite the consumption of a wide variety of soy foods. One primary
      reason is that they consume fermented rather than non-fermented soy foods. In
      order to assess the varying effects of fermented and non-fermented soy intake on
      GC risk in these populations, we conducted a meta-analysis of published reports.
      Twenty studies assessing the effect of the consumption of fermented soy food on
      GC risk were included, and 17 studies assessing the effect of the consumption of
      non-fermented soy food on GC risk were included. We found that a high intake of
      fermented soy foods was significantly associated with an increased risk of GC
      (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.02-1.44, I(2) = 71.48),
      whereas an increased intake of non-fermented soy foods was significantly
      associated with a decreased risk of GC (overall summary OR = 0.64, 95% CI = 0.54
      0.77, I(2) = 64.27). These findings show that a high level of consumption of non
      fermented soy foods, rather than fermented soy foods, is important in reducing GC
      risk.

PMID- 21070480
TI  - The idiotype (Id) cascade in mice elicited the production of anti-R24 Id and anti
      anti-Id monoclonal antibodies with antitumor and protective activity against
      human melanoma.
AB  - Gangliosides have been considered as potential targets for immunotherapy because
      they are overexpressed on the surface of melanoma cells. However, immunization
      with purified gangliosides results in a very poor immune response, usually
      mediated by IgM antibodies. To overcome this limitation, we immunized mice with
      R24, a monoclonal antibody (mAb) that recognizes the most tumor-restricted
      ganglioside (GD3); our goal was to obtain anti-idiotype (Id) antibodies bearing
      the internal image of GD3. Animals produced anti-Id and anti-anti-Id antibodies.
      Both anti-Id and anti-anti-Id antibodies were able to inhibit mAb R24 binding to
      GD3. In addition, the anti-anti-Id antibodies were shown to recognize GD3
      directly. Anti-Id and anti-anti-Id mAb were then selected from two fusion
      experiments for evaluation. The most interesting finding emerged from the
      characterization of the anti-anti-Id mAb 5.G8. It was shown to recognize two
      different GD3-expressing human melanoma cell lines in vitro and to mediate tumor
      cell cytotoxicity by complement activation and antibody-dependent cellular
      cytotoxicity. The biological activity of the anti-anti-Id mAb was also tested in
      a mouse tumor model, in which it was shown to be a powerful growth inhibitor of
      melanoma cells. Thus, activity of the anti-anti-Id mAb 5.G8 matched that of the
      prototypic anti-GD3 mAb R24 both in vitro and in vivo. Altogether, our results
      indicate that the idiotype approach might produce high affinity, specific and
      very efficient antitumor immune responses.

PMID- 21070482
TI  - Ultrasound detects joint damage and bleeding in haemophilic arthropathy: a
      proposal of a score.
AB  - Haemarthrosis triggers haemophilic arthropathy (HA) because bleeding starts
      synovitis immediately, damages cartilage and leads to loss of function and
      disability. The aim of our study was to investigate the capacity of
      ultrasonography (US) in detecting bleeding and joint damage in HA. The joints of
      62 patients (pts) with haemophilia A or haemophilia B were consecutively
      evaluated and scored (score ranging from 0 to 21) for effusion (E), bone
      remodelling (BR), cartilage damage (CD), synovial hypertrophy (SH), haemosiderin
      (H), osteophytes (O), haemarthrosis (Hae), erosion (Er) and fibrotic septa (FS)
      with US. X-rays [Pettersson Score (PXS)] were performed in 61 patients and
      clinical evaluation [World Federation Haemophiliac orthopaedic score (WFHO)] was
      performed in all patients. A total of 20 healthy subjects and 20 patients
      affected by Rheumatoid Arthritis (RA) were used as controls. Power Doppler US
      (PDUS) was performed in all patients on the knee, ankle and elbow joints. A total
      of 83 joints were studied (50 knees; 12 elbows and 21 ankles). US showed effusion
      in 57 joint, bone remodelling in 62, cartilage damage in 64, synovial hypertrophy
      in 45, haemosiderin in 39, osteophytes in 30, haemarthrosis in 24, erosion in 5
      and fibrotic septa in 3. The X-rays score showed remodelling in 47 joints,
      narrowing joint space in 44, displacement/angulation in 39, osteoporosis in 42,
      subchondral irregularity in 44, subchondral cyst formation in 37, osteophytes in
      36 and erosions in 25. The US score in healthy subjects was always <= 5 (range 0
      to 4). In haemophiliacs, 34 of 83 joints showed US score <= 5, and 49 US score >
      5. Joints with US score <= 5 had a low PXS (SRCC = 0.375, P < 0.01) and joints
      with US score > 5 showed a high PXS (SRCC = 0.440, P < 0.01). A significant
      correlation between US score and PXS for bone remodelling [Spearman's rho
      Correlation Coefficient (SRCC) = 0.429, P < 0.01] and for osteophytes (SRCC =
      0.308, P < 0.05) was found. The correlation between the US score and number of
      bleedings in 83 joints was very significant (SRCC = 0.375, P < 0.01). A total of
      24 bleeding joints were identified and verified with aspiration of haematic
      fluid. US may detect bone and cartilage alterations and synovitis. Indeed, PDUS
      identified bleeding also in asymptomatic joints and was able to show different
      entity of haemarthrosis. US may be a feasible and reliable tool to evaluate joint
      modifications in HA.

PMID- 21070483
TI  - Difference in TFPI levels between haemophilia A and B patients.

PMID- 21070481
TI  - Prophylaxis therapy in haemophilia A: current situation in Spain.
AB  - The Spanish Epidemiological Study in Haemophilia carried out in 2006 enrolled
      2400 patients [2081-86.7% with haemophilia A (HA) and 319-13.3% with haemophilia
      B]; 465 of them (19.4%) were on prophylaxis. These rates were higher in patients
      with severe haemophilia (45.4%) and severe paediatric cases (72.5%). On the basis
      of information recorded in this study, we analysed the current situation of
      prophylaxis therapy administered to patients with HA in Spain, as well as their
      orthopaedic status. Prophylaxis was used in 399 (19.2%) patients with HA; such
      prophylaxis was primary (PP) in 20.3% and secondary (SP) in 75.9% of cases. Among
      severe HA patients, 313 (45.9%) were on prophylaxis (22.3% on PP and 74.7% on
      SP). Taking into account the patients' age, 34.7% of severe HA adults were on
      prophylaxis (6% PP and 92.1% SP), whereas 71.5% of severe HA paediatric patients
      (40.5% PP and 55.4% SP) received this kind of treatment. Established haemophilic
      arthropathy (EHA) was detected in 142 from 313 severe HA patients (45.3%) on
      prophylaxis, but only in 2.9% of patients under PP vs. 59% of patients receiving
      SP. There was no EHA in adult severe HA patient on PP, whereas 70.4% on SP had
      joint damage (P < 0.00001). Among paediatric severe HA patients, EHA was detected
      in 3.3% under PP and 37.8% under SP (P < 0.00001). In conclusion, our data
      suggest that an early initiation of prophylaxis avoids EHA in the long-term in
      patients with severe HA. We should emphasize the early onset of prophylaxis
      regimens.

PMID- 21070484
TI  - Popliteal cyst rupture in a haemophiliac presenting as refractory recurrent right
      lower leg haemorrhage.

PMID- 21070485
TI  - Range of motion measurements: reference values and a database for comparison
      studies.
AB  - Many diseases and injuries can impair joint mobility. Normal reference values are
      needed to determine extent of impairment to assess and monitor joint motion.
      There is very little published data describing normal joint range of motion (ROM)
      for healthy men and women across a wide span of ages. We enrolled male and female
      subjects aged between 2 and 69 years who were free from conditions that could
      potentially limit joint mobility for the study. Nine licensed physical therapists
      used universal goniometers to determine passive joint motion bilaterally of elbow
      flexion, extension, supination and pronation, shoulder flexion, hip flexion and
      extension, knee flexion and extension, and ankle dorsiflexion and plantarflexion.
      Descriptive statistics were calculated for male and female subjects in four age
      groups: 2-8, 9-19, 20-44 and 45-69 years. Joint ROM measurements were obtained on
      a total of 674 (53.6% female) healthy, normal subjects aged 2-69 years. Female
      subjects had greater joint mobility in all age groups in nearly all joints and
      the gender difference was most obvious in measures of ankle plantarflexion, elbow
      pronation and supination. Range of motion average values for all joints decreased
      with advancing age for both men and women and, in most cases, were significantly
      different than most commonly used normative values. Our study of ROM measurements
      taken by trained physical therapists on a large sample of healthy individuals
      revealed significant gender- and age-related variation that may be an important
      consideration in patient assessment.

PMID- 21070486
TI  - Haemophilic arthropathy: the usefulness of intra-articular oxytetracycline
      (synoviorthesis) in the treatment of chronic synovitis in children.
AB  - Synoviorthesis is already widely used in the treatment of chronic haemophilic
      synovitis. The aim of this study was evaluate the effectiveness of
      oxytetracicline synoviorthesis on the frequency of haemarthrosis in haemophilic
      children with chronic synovitis and its impact on joint function. Between January
      2001 and October 2006, we performed 34 synoviorthesis in 28 paediatric patients
      (6-16 years old) with diagnosis of haemophilic arthropathy stage I-II. At each
      joint were administered five doses of oxytetracycline for five consecutive weeks
      at doses of 100 mg in elbow and ankle and 250 mg in the knee. The frequency of
      haemarthrosis and range of joint mobility were evaluated before and after of
      treatment. The results were analysed with Student t-test and descriptive
      statistics. Thirty-four joints were treated, including 20 knees (58.8%), eight
      elbows (23.5%) and six ankles (17.6%). Median follow-up was 46.3 months (range 12
      71 months). The frequency of haemarthrosis was recorded before treatment 47.3
      year(-1) (range 12-96, P < 0.0001) and decreased to 3.5 year(-1) (range 0-15, P =
      0.0119) after treatment. The range of joint motion in flexion-extension before
      treatment was 84.9 degrees , while after this was 97.5 degrees  (P = 0.0119). The
      synoviorthesis with oxytetracycline has shown a favourable effect in the
      treatment of chronic haemophilic synovitis in reducing the frequency of
      haemarthrosis and improvement was observed consistently in the range of motion.

PMID- 21070487
TI  - Informativeness of a novel multiallelic marker-set comprising an F8 intron 21 and
      three tightly linked loci for haemophilia A carriership analysis.
AB  - The extraordinary heterogeneous nature of the deleterious mutations in the F8
      gene that lead to functional deficiency of clotting factor VIII in haemophilia A
      makes routine direct mutation profiling difficult. When direct mutation analysis
      cannot be performed or a causative/candidate mutation is not found, a second-line
      approach to track the defective F8 gene within at-risk families is linkage
      genetic analysis with, tried-and-tested, F8-intragenic and/or extragenic non
      recombining multiallelic short tandem repeats (STR). Although several typing STR
      loci within and around F8 have been described, there is need for improving
      assessment, because the combined informativeness of available assays rarely
      reaches 100%. Here, we characterized a newly identified 0.28 cM-resolution marker
      set, consisting of a dinucleotide STR located on F8 intron 21 (F8Int21; [AC](n))
      and three extragenic tetranucleotide STR located on GAB3 intron 1 (GAB3Int1;
      [TAAA](n)) and TMLHE intron 1 (TMLHEInt1.1; [GAAA](n) and TMLHEInt1.3;
      [ATTC](n)). Heterozygosity rates determined in 100 unrelated females ranged from
      0.25 (GAB3Int1) to 0.63 (F8Int21). The set rendered a combined informativeness of
      0.91 for at least one marker and 0.60 for a minimum of two loci, with at least
      one F8-intragenic. Multiallelic interlocus non-random association analysis
      revealed that GAB3Int1 is not in significant gametic disequilibrium (GD) with
      F8Int21, F8Int9.2, TMLHEInt1.3 or TMLHEInt1.1. Gametic disequilibrium breakdown
      attests historical recombination between GAB3Int1 and the F8 gene. Through
      computational analysis of reference assembly sequence data, we note in the GD
      breakdown region and in the F8 gene a higher than average density of the 13-mer
      CCNCCNTNNCCNC consensus motif, commonly associated with recombination hotspots.

PMID- 21070488
TI  - A flow cytometry evaluation of anti-FVIII antibodies: correlation with ELISA and
      Bethesda assay.
AB  - In this study, we describe a flow cytometry (FC) system for detecting antibodies
      to factor VIII (FVIII) and compare its results with those of enzyme-linked
      immunosorbent assay (ELISA) that detects both inhibitory (I-Ab) and non
      inhibitory (NI-Ab) antibodies and the Nijmegen modification of the Bethesda
      method, detecting I-Ab. FC was set up in our laboratory. Recombinant FVIII
      (rFVIII) was coupled to microspheres (FVIII-m) and reacted with different plasma
      dilutions. Microspheres without rFVIII were used as control (control-m). Captured
      anti-FVIII antibodies were detected using anti-human IgG. Plasma samples from the
      following patients with severe haemophilia A (SHA) patients were evaluated: 17 P
      (patients without I-Ab, <0.5 BU mL(-1)); 13 PI (patients with I-Ab, 1.1-8200 BU
      mL(-1)). Of these 13, two PI were referred during immune tolerance induction
      (ITI), and plasmas from 12 healthy donors (HD) were evaluated. Semiquantitative
      results were given as an index (the highest mean fluorescence intensity ratio
      between FVIII-m and control-m multiplied by the inverse of the corresponding
      plasma dilution). Both plasma and serum were suitable for the test. FC agreed
      with the Bethesda method (r = 0.8; P = 0.0001). FC and ELISA had 80% of
      coincidence. Four of 17 patients (23.5%) had NI-Ab by FC, and two of them
      developed high levels of I-Ab later on. This test provides a useful alternative
      for measuring FVIII antibodies supplementing Bethesda assay. FC is fast and easy
      to perform. No more than 200 MUL of plasma or serum is required especially making
      it useful for paediatric patients.

PMID- 21070489
TI  - High-resolution imaging of multimers can detect von Willebrand's disease type 2A
      even if ristocetin cofactor is higher than von Willebrand antigen.

PMID- 21070490
TI  - A comparison between the complications and long-term outcome of hip and knee
      replacement therapy in patients with and without haemophilia; a controlled
      retrospective cohort study.
AB  - The outcomes of total knee arthroplasty (TKA) and total hip arthroplasty (THA) in
      patients with haemophilia have not been compared with other patient populations.
      The aim of this study was to compare the results of joint replacement therapy in
      patients with and without haemophilia retrospectively. This is a controlled
      retrospective cohort study. The complications and long-term results of 21 TKAs
      and 6 THAs performed in 22 haemophilia patients were compared with those of 42
      TKAs and 12 THAs in patients without bleeding disorders. Patients were matched
      for type of arthroplasty, gender, year of surgery and age. Blood loss, infection
      rate, revision, implant survival and function as judged by the patient were
      recorded. Haemarthrosis occurred in 14 (52%) of the 27 arthroplasties performed
      in the haemophilia patients, while four bleedings were recorded in the 54
      arthroplasties in the control group (7%, P < 0.001). All bleeds occurred in TKAs.
      In the patient group, two infections (7%, both in TKAs) occurred compared to
      seven (13%, 6/7 in TKAs) in the control group (NS). In the haemophilia patients,
      all but one (96%) arthroplasties were still in situ at the end of follow-up, vs.
      44 (81%, NS) in the control group. For TKAs, survival was 20/21 vs. 34/42
      respectively (P = 0.25). Subjective function was good in 22/27 (81%; 76% in TKAs)
      arthroplasties in haemophilia patients, vs. 40/54 (74%; 71% in TKAs) in controls.
      Haemophilia patients experienced significantly more haemarthroses, but no more
      infections and they have an excellent implant survival compared with non
      haemophilia controls.

PMID- 21070491
TI  - Massive retroperitoneal haemorrhage in a neonate with severe haemophilia A.

PMID- 21070492
TI  - Successful treatment of an injury bleeding on a patient suffering from mild von
      Willebrand's disease and predisposition to allergic diseases, with recombinant
      factor VIIA.

PMID- 21070493
TI  - Patient and parent preferences for haemophilia A treatments.
AB  - Little is known about the relative importance of factor VIII (FVIII) treatment
      attributes to haemophilia A patients and their willingness to accept trade-offs
      among these attributes. To quantify patient and parent preferences for FVIII
      treatments and compare the relative importance of treatment attributes. Adult
      patients and parents of children with severe haemophilia A in the US completed a
      web-enabled, choice-format conjoint survey that presented a series of 12 trade
      off questions, each including a pair of hypothetical treatment profiles. Each
      profile was defined by percent of bleeds stopped with one or two infusions,
      chance of developing an inhibitor, risk of viral infection, preparation volume,
      dosage strengths available, and history of supply shortage. Trade-off questions
      were based on a D-optimal experimental design. Preference weights for attribute
      levels were estimated using random-parameters logit. One hundred and forty seven
      subjects completed the survey. Over the ranges of attribute levels included in
      the study, risk of viral infection was the most important attribute. Remaining
      attributes were ranked in decreasing order of importance as follows: chance of
      developing an inhibitor, dosage strengths available, percent of bleeds stopped
      with one or two infusions, history of supply shortage, and preparation volume.
      Risk of viral infection was 6.0 times as important as percent of bleeds stopped
      with one or two infusions and 2.7 times as important as the chance of developing
      an inhibitor. While risk of viral infection was the most important attribute,
      this research demonstrates that many FVIII treatment attributes are important in
      the decision-making process.

PMID- 21070494
TI  - Focusing on haemophilia B: prophylaxis in Spanish patients.

PMID- 21070495
TI  - Dengue virus infection in haemophilic patients: aggravation of bleeding risk.

PMID- 21070496
TI  - Pharmacokinetics of Optivate((r)), a high-purity concentrate of factor VIII with
      von Willebrand factor, in patients with severe haemophilia A.
AB  - Optivate((r)) is a high purity factor VIII/von Willebrand factor (FVIII/VWF)
      concentrate, which is manufactured using two antiviral processes:
      solvent/detergent and terminal dry heating (80  degrees C for 72 h). A
      multicentre, non-randomized open-label study in 15 patients was conducted to test
      the pharmacokinetics (PK) of Optivate((r)). PK variables were analysed for the
      patients' prior FVIII product (PK1), their first dose of Optivate((r)) (PK2) and
      at 3 months therapy (PK3). Mean non-compartmental half-lives (h) were 14.1, 12.4
      and 12.1, respectively (P = 0.45), mean clearances (mL h(-1) kg(-1)) were 3.6,
      3.2 and 3.1, respectively (P = 0.051), MRTs (h) were 19.0, 17.3 and 17.4,
      respectively (P = 0.39) and mean AUC(0-48h) (h IU mL(-1)) were 14.3, 15.4 and
      16.6, respectively (P = 0.051) and mean AUC(0-infinity) (h IU mL(-1)) were 15.9,
      16.4 and 17.9, respectively (P = 0.18). The recovery data from this PK study was
      aggregated with recovery data collected from another study, with similar design
      but devoid of the other PK measurements. A total of 309 recoveries were conducted
      in 70 patients. The overall mean recovery per subject across 27 Optivate((r))
      batches was 2.7 IU dL(-1) per IU kg(-1). There were no clinical differences
      between Optivate((r)) and other FVIII products, and except for volume of
      distribution (Vd), no statistically significant differences were seen with
      respect to any of the other PK variables, or in recovery between weeks 0 and 12.
      Therefore, the PK of FVIII is not affected by the processes used to manufacture
      Optivate((r)), which can be expected to be effective in the management of
      patients with haemophilia A.

PMID- 21070497
TI  - Home treatment of haemophilia patients with inhibitors.
AB  - Bleeding episodes in patients with inhibitors can be challenging to treat.
      Clinical guidelines recognize the importance of early treatment, ideally within 2
      h of the onset of bleeding. On-demand haemophilia care at home has been shown to
      reduce the time between recognition of the symptoms of bleeding and initiation of
      treatment. Rapid resolution of bleeding is associated with longer-term benefits
      for the patient. Effective haemophilia care at home depends on patients and
      carers taking greater responsibility for treatment; however, many find this
      difficult. Education can help raise awareness of haemophilia treatment at home
      and provide helpful information for patients/carers. The haemophilia nurse has a
      key role in providing this support and education. This review discusses a number
      of recent guidelines and educational materials for haemophilia home care
      identified during a literature survey. The survey shows that most materials were
      not validated. In addition, the survey shows limited effectiveness data on
      techniques for training haemophilia patients about home care. Further education
      resources and research in the treatment of haemophilia at home are required.

PMID- 21070498
TI  - Evaluation of an automated platelet-based assay of ristocetin cofactor activity.
AB  - von Willebrand's disease (VWD) is regarded as the most common congenital bleeding
      disorder, and although not available in all laboratories von Willebrand factor
      (VWF) activity is most frequently assessed as ristocetin cofactor (VWF:RCo). This
      test can be technically challenging, is subject to poor sensitivity (~20 IU dL(
      1) VWF:RCo) and has a high degree of inter- and intra-assay imprecision
      [coefficient of variation (cv) > 25%]. We studied an automated assay using a
      combined fixed platelet/ristocetin reagent (BC von Willebrand reagent, Siemens
      Healthcare Diagnostics) on the CS-2000i analyser (Sysmex UK Ltd). Initially inter
      and intra-assay imprecision was assessed. The automated method showed good day
      to-day reproducibility and linearity of standard curves. This technique, also
      gave low intra- and inter-assay imprecision using commercial normal (cv < 4.5%)
      and pathological (cv < 8.1%) control plasmas. We then compared automated
      technique results from 30 healthy normal subjects and 39 VWD patients to those
      obtained using standard aggregometry (Bio/Data, PAP4) with lyophilised fixed
      platelets (Helena BioSciences) and ristocetin (American Biochemical and
      Pharmaceutical Ltd). The automated method had a sensitivity limit of
      approximately 10 IU dL(-1) vs. 20 IU dL(-1) for aggregometry. Samples giving
      results within the aggregometry measurable range (n = 50) exhibited good
      correlation with the automated technique (median 70 IU dL(-1), range 7-184 IU dL(
      1); and 64 IU dL(-1), 6-138 IU dL(-1) respectively; R(2) = 0.85). We subsequently
      compared 3 different batches of BC von Willebrand reagent, using a second group
      of normal subjects and VWD patients (n = 35, 55-139 IU dL(-1) and n = 30, <10-50
      IU dL(-1)). The CS-2000i results exhibited no clinically significant variation
      between batches (mean cv = 7%). The automated VWF:RCo assay offers a more
      sensitive, reproducible, robust and less laborious alternative to standard
      aggregometry.

PMID- 21070499
TI  - Influence of the type of F8 gene mutation on inhibitor development in a single
      centre cohort of severe haemophilia A patients.
AB  - The development of neutralizing antibodies against factor VIII (FVIII) is a major
      complication of treatment with FVIII in patients with severe haemophilia A. This
      study was designed to describe the relationship between the type and location of
      the factor 8 (F8) gene mutation and the development of clinically relevant
      inhibitors in patients with severe haemophilia A. We conducted a single centre
      cohort study among 318 consecutive patients (baseline FVIII activity level <0.01
      IU mL(-1)) born between 1934 and 2007 who were treated with FVIII on at least 50
      exposure days. The primary outcome was clinically relevant inhibitor development,
      defined as the occurrence of at least two positive inhibitor titres and a
      decreased recovery. Clinically relevant inhibitors were diagnosed in 14% (43) of
      patients (30 high-titre). The cumulative incidence of inhibitor development was
      18% (35 of 200) in high-risk gene defects (67% in patients with large deletions,
      30% in patients with nonsense mutations, 15% in patients with intron 1 or 22
      inversions) and 7% (8 of 118) in low-risk gene defects (7% in patients with small
      deletions and insertions, 6% in patients with missense mutations, 8% in patients
      with splice site mutations). In patients with point mutations, the cumulative
      risk of developing inhibitors was highest in patients with mutations in the A3
      and C2 domains (13% and 17% respectively). In conclusion, in agreement with
      earlier observations, the type and location of the F8 gene mutation were
      important determinants of inhibitor development in patients with severe
      haemophilia A.

PMID- 21070500
TI  - Orthopaedic evaluation in children with severe haemophilia A or B submitted to
      primary prophylaxis therapy in a coagulopathy treatment centre.
AB  - There is a lack of publications concerning the use of primary prophylaxis in
      developing countries. The aim of this study was to evaluate the effectiveness of
      primary prophylaxis therapy in preventing the development of arthropathy in
      children with severe haemophilia A or B. From January 1999 to April 2009, a
      prospective study was carried out involving 39 patients with severe haemophilia A
      or B. These haemophilia A and haemophilia B patients received 20-40 UI kg(-1) of
      factors VIII and IX, three and two times per week, respectively. The patients
      were followed up by a multidisciplinary team. The analysis was carried out in 23
      patients who had been on prophylaxis therapy for at least 12 months. The
      orthopaedic evaluation was performed according to the recommendations of the
      Orthopedic Advisory Committee of the World Federation of Hemophilia, by
      evaluating pain and bleeding, and by conducting physical examination and
      radiological assessment (Pettersson's Joint Score and magnetic resonance): 82.6%
      of patients who had used the factor regularly did not present any clinical or
      radiographic changes in the studied joints; 17.4% used the factor irregularly at
      the beginning of the treatment and of those, most patients presented mild changes
      in the joints; and 4.3% presented transient knee and ankle pain in spite of
      regular factor use. The preliminary results of primary prophylaxis confirm its
      effectiveness in preventing haemophilic arthropathy. Socioeconomic factors did
      not play a significant role.

PMID- 21070501
TI  - Treatment related factors and inhibitor development in children with severe
      haemophilia A.
AB  - With the advent of modern factor replacement therapy the most important remaining
      obstacle to successful treatment in haemophilia A is the development of
      inhibitory antibodies against Facto VIII (FVIII). This retrospective case control
      study examined genetic variables and early treatment patterns in severe
      haemophilia A patients who subsequently developed clinically significant
      inhibitors to FVIII compared with matched controls who did not. Seventy eight
      inhibitor patients were identified from 13 UK centers over 25 years (1982-2007).
      For each case an age matched control was selected. Data on potential genetic and
      treatment related risk factors were collected for cases and controls. Treatment
      related data was collected for the first 50 exposure days (EDs) for controls or
      up to inhibitor development for cases. Risk factors were compared for
      significance by univariate and multivariate analysis. Of the genetic risk
      factors, major defects in the FVIII gene and non-caucasian ethnicity were each
      responsible for approximately 5-fold increases in inhibitor risk. When treatment
      related variables are considered, high intensity treatment increased inhibitor
      risk around 2.5 fold whether represented by the presence of peak treatment
      moments or by high overall treatment frequency. This finding was significant
      regardless of the timing of the high intensity treatment. Periods of intense
      treatment associated with surgery for porta-cath insertion were however not found
      to be associated with increased inhibitor risk. No association was shown between
      inhibitor development and age at first FVIII exposure, type of FVIII product, or
      the use of regular prophylaxis. This study confirms treatment-related factors as
      important risks for inhibitor development in Haemophilia A.

PMID- 21070502
TI  - Interleukin-28B polymorphisms are associated with hepatitis C virus clearance and
      viral load in a HIV-1-infected cohort.
AB  - Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are
      able to clear HCV spontaneously. Differences in host genetics are believed to
      affect the outcome of HCV infection. We analysed an exonic, a promoter and an
      intronic single nucleotide polymorphism (SNP) of the interferon-lambda3 coding
      interleukin (IL)-28B gene to study the relationship between IL28B SNPs and
      outcome of HCV infection. Among 206 HIV-1-infected Europeans with evidence of HCV
      infection, 47 (23%) individuals had cleared HCV and 159 (77%) had developed
      chronic infection. The exonic rs8103142 CT, the promoter rs12979860 CT and the
      intronic rs11881222 AG genotypes were associated with a decreased HCV clearance
      rate with adjusted odds ratios (aOR) of 0.3 (95% CI, 0.1-0.7), 0.4 (95% CI, 0.2
      0.8) and 0.4 (95% CI, 0.2-0.8), respectively. The haplotype block TCG CTA was
      associated with a decreased HCV clearance rate (aOR 0.4, 95% CI, 0.2-0.8).
      Further, we found significant differences in HCV RNA levels among individuals
      chronically infected with HCV genotype 1 for rs8103142 and rs12979860 (P <=
      0.05). Chronically infected individuals with HCV genotype 3 and with the
      favourable haplotype block CTA CTA had higher median HCV RNA levels than
      individuals with unfavourable haplotype blocks (P <= 0.05). Our findings suggest
      that IL28B may account for some differences in HCV outcome but that other factors
      including the viral genotype, host genetics and the host-virus interaction are
      likely to influence the outcome of HCV infection.

PMID- 21070503
TI  - Suicide risk in hepatitis C and during interferon-alpha therapy: a review and
      clinical update.
AB  - Chronic hepatitis C (CHC) affects over 170 million individuals worldwide and is a
      growing public health concern. Despite the availability of CHC treatment,
      specifically interferon-alpha and ribavirin, treatment of CHC is limited by
      concerns about psychiatric side effects including risks of suicide. Although
      depression has been the focus of neuropsychiatric complications from interferon
      alpha (IFNalpha), emerging evidence has contributed to our understanding of
      IFNalpha-induced suicidal ideation and attempts. Using Pubmed, we performed a
      literature review of all English articles published between 1989 and April 1,
      2010 on suicide in untreated and IFNalpha-treated patients with CHC. References
      in all identified review articles were scanned and included in our review. A
      total of 17 articles were identified. Studies have suggested that the first 12
      weeks of IFNalpha therapy are the high-risk period. Moreover, the emergence of
      suicidal ideation can be linked to neuropsychiatric abnormalities, specifically
      serotonin depletion. Pretreatment with antidepressant treatment should be
      reserved for high-risk groups, as this may reduce the risk of depression and thus
      decrease the suicide risk indirectly. Although there is a paucity of literature
      on suicide and suicide risk during IFNalpha therapy for CHC, recent studies on
      IFNalpha-induced depression have provided some potential insights into suicide in
      this patient population. Further research examining the effects of
      pharmacological and nonpharmacological interventions on suicide risk during
      IFNalpha treatment is needed.

PMID- 21070504
TI  - Serum lipids and their associations with viral levels and liver disease severity
      in a treatment-naive chronic hepatitis C type 1-infected cohort.
AB  - In patients with chronic hepatitis C virus (HCV) infection, steatosis and
      fibrosis have been shown to be inversely associated with total cholesterol (TC)
      and low-density lipoprotein cholesterol. Steatosis and fibrosis have also been
      found to be associated with triglyceride (TG) levels; though, the direction of
      the relationship is inconsistent across studies. The objective of this study was
      to assess whether viral level and histological factors are associated with the
      serum lipid profile in a treatment-naive cohort with chronic HCV genotype 1
      infection. Participants were from the prospective Study of Viral Resistance to
      Antiviral Therapy (Virahep-C). Fasting lipid profiles were analysed for 160
      African Americans and 170 Caucasian Americans. Linear regression was used to
      evaluate associations of each lipid with viral load and liver disease. TG levels
      were significantly and directly associated with HCV levels (P = 0.0034) and
      steatosis (P < 0.0001). Other lipid parameters were significantly lower in those
      with fibrosis [HDLc (P = 0.001) and TC levels (P = 0.004)] than in those without
      fibrosis. In patients with HCV genotype 1 infection, more severe liver disease
      was associated with lower lipid levels, with the exception of TG levels that were
      directly related to steatosis. The direct relationship between viral load and TG
      levels is consistent with proposed the mechanisms of very low density
      lipoprotein/HCV particle secretion. In contrast, the direct relationship between
      TG level and steatosis is inconsistent with posited mechanisms of HCV-induced
      steatosis, a possible reflection of HCV genotype 1 infection and a metabolic
      aetiology of steatosis.

PMID- 21070505
TI  - Multiple polymorphisms in genes of the adrenergic stress system confer
      vulnerability to alcohol abuse.
AB  - Environmental factors such as stress influence both the predisposition to and
      development of alcoholism, as well as have significant implications for
      alcoholism relapse. One predominant biological response to acute stress is the
      release of norepinephrine, which activates the peripheral stress response and
      also the hypothalamic-pituitary-adrenal axis. We aimed to examine the role of two
      genes of the adrenergic system (SLC6A2 and ADRA2A) in alcoholism by genotyping 21
      SNPs in 785 adult alcohol-dependent patients and 1237 controls. Two single
      nucleotide polymorphisms (SNP) (rs36020 and rs36029) in SLC6A2 were significantly
      associated with alcoholism [false discovery rate corrected P-value (FDR) P =
      0.007]. Two SNPs in ADRA2A (rs521674 and rs602618) were associated with a
      positive family history of alcoholism (FDR P <= 0.05). A combined SNP-set
      analysis was also carried out to determine the risk of harbouring multiple
      alcohol risk alleles across SLC6A2 and ADRA2A. Logistic regression analysis
      revealed that an increase in the number of alcohol risk alleles increased the
      risk for alcoholism (P = 0.000567, odds ratio = 1.75, 95% confidence interval
      1.26-2.44). A three-SNP haplotype consisting of rs187715, rs36020 and rs40147
      alleles, AGC, was also found, which was significantly over-represented in cases
      compared with controls (61% versus 56%). We therefore demonstrate an association
      of SLC6A2 and ADRA2A with adult alcoholism. These data confirm the relevance of
      the adrenergic stress system when considering genetic predisposition to alcohol
      dependence and suggest that SLC6A2 and ADRA2A should be studied in additional
      alcohol-dependent cohorts.

PMID- 21070506
TI  - ERK1/2 protein and mRNA levels in human blood are linked to smoking behavior.
AB  - From studies in cultured cells and animal models, nicotine and alcohol are known
      to regulate extracellular signal-regulated kinase 1 and 2 (ERK1/2). Alterations
      of ERK1/2 are thought to contribute to the drugs' rewarding effects. Accumulating
      evidence supports the importance of ERK1/2 in the molecular pathophysiology of
      depression and affective regulation in the hippocampus. We recently showed that
      the expression and phosphorylation of cyclic adenosine monophosphate response
      element (CRE)-binding protein (CREB) in human buffy coat were associated with
      smoking behavior. Because ERK1/2 is known to effect phosphorylation of CREB, the
      aim of the present study was to further elucidate whether cigarette smoking leads
      to alterations in terms of ERK1/2 in human buffy coat as well. In a comparison of
      53 smokers with 146 non-smoking controls, we found significantly higher levels of
      ERK1/2 protein (P=0.004). In contrast, phospho-ERK1/2, phospho-/total-ERK1/2
      ratio, mRNA-ERK1 and mRNA-ERK2 were not significantly different. Multiple
      regression analysis revealed a significant relation among the number of
      cigarettes smoked daily (R(2)=0.266, P=0.003), the Fagerstrom Test for Nicotine
      Dependence score (R(2)=0.149, P=0.032) and the mRNA expression of ERK1. Moreover,
      our analysis suggests that the mRNA expression of ERK2 might be linked to mood
      (model summary: R(2)=0.087, P=0.019; mRNA-ERK2: P=0.026). Given that the ERK1/2
      signaling pathway plays an important role in the physiology and pathophysiology
      of affective and addictive behavior, our findings provide a rationale basis for
      additional mechanistic studies that may lead to the development of novel
      signaling pathway selective therapeutics in humans.

PMID- 21070507
TI  - A C17T polymorphism in the mu opiate receptor is associated with quantitative
      measures of drug use in African American women.
AB  - Previous studies of the association of the C17T polymorphism of the mu opiate
      receptor gene with substance dependence compared cases with substance dependence
      to controls and usually found no significant association. However, the studies
      were limited by small sample size-no study had more than 12 subjects with the TT
      genotype, a genotype that is rare in white and Asian subjects. Moreover, drug use
      is not dichotomous but follows a spectrum from non-use to modest, intermittent
      use, to use several times daily. We asked whether the Kreek-McHugh-Schluger
      Kellogg (KMSK) scales for alcohol, cocaine, opiates and tobacco that quantify
      substance use during the time of a subject's maximal use might be more sensitive
      measures than dichotomous outcomes. We administered the KMSK scales and completed
      C17T genotyping on 1009 human immunodeficiency virus (HIV)-infected and 469 HIV
      uninfected women in The Women's Interagency HIV Study, an ongoing study of HIV in
      women. Forty-two of the 697 African American, 1 of the 182 Hispanic and none of
      the 161 white women had the TT genotype. KMSK cocaine, alcohol and tobacco scores
      were significantly higher in the African American women with the TT genotype (P =
      0.008, 0.0001, and 0.006, respectively), but opiate scores were not. Ordinal
      regression models controlling for HIV serostatus, age, education, and income had
      odds ratios for the TT genotype for predicting alcohol, tobacco, cocaine and
      opiates scores of 2.1 (P = 0.02), 2.4 (P = 0.0004), 2.0 (P = 0.03) and 1.9 (P =
      0.07). We conclude that the TT genotype of OPRM1 may increase the risk of
      substance use and abuse.

PMID- 21070508
TI  - White matter microstructure in opiate addiction.
AB  - Heroin addiction has been associated with impaired neuronal connectivity and
      cognitive deficits. One mechanism that potentially explains these findings is
      alterations in white matter connectivity secondary to chronic opiate use.
      However, few studies have quantitavely examined white matter deficits in opiate
      addiction (OA). Here, we investigated white matter microstructure in OA using
      diffusion tensor imaging (DTI). We performed voxel-wise analysis of fractional
      anisotropy (FA) in 24 participants with OA and 29 healthy controls. The OA group
      showed reduced FA in multiple pathways including the corpus callosum, thalamic
      radiation and inferior longitudinal fasciculus. This FA reduction was mainly the
      result of increased radial diffusivity (lambda(?)), indicative of myelin
      pathology. Longer duration of OA was also associated with axonal diffusivity
      (lambda(1)), most robustly in superior longitudinal fasciculi and right frontal
      white matter suggesting axonal injury in long-term users. Together, the findings
      indicate that chronic OA use has widespread and diverse effects on neuronal
      connectivity and function.

PMID- 21070510
TI  - Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated
      with antisocial personality disorder not co-morbid with alcoholism.
AB  - Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking
      behavior or alcoholism because the ALDH2*2 allele protects against the risk of
      developing alcoholism. The mechanism provides that the ALDH2 gene's protective
      effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene
      with neurotransmitters, such as dopamine, is suggested to be related to
      alcoholism. Because alcoholism is often co-morbid with antisocial personality
      disorder (ASPD), previous association studies on antisocial alcoholism cannot
      differentiate whether those genes relate to ASPD with alcoholism or ASPD only.
      This study examined the influence of the interaction effect of the ALDH2*1*1,
      *1*2 or *2*2 polymorphisms with the dopamine 2 receptor (DRD2) Taq I polymorphism
      on ASPD. Our 541 Han Chinese male participants were classified into three groups:
      antisocial alcoholism (ASPD co-morbid with alcohol dependence, antisocial ALC; n
      = 133), ASPD without alcoholism (ASPD not co-morbid with alcohol dependence,
      antisocial non-ALC; n = 164) and community controls (healthy volunteers from the
      community; n = 244). Compared with healthy controls, individuals with the DRD2
      A1/A1 and the ALDH2*1/*1 genotypes were at a 5.39 times greater risk for
      antisocial non-ALC than were those with other genotypes. Our results suggest that
      the DRD2/ANKK1 and ALDH2 genes interacted in the antisocial non-ALC group; a
      connection neglected in previous studies caused by not separating antisocial ALC
      from ASPD. Our study made this distinction and showed that these two genes may be
      associated ASPD without co-morbid alcoholism.

PMID- 21070509
TI  - Examining the role of oxytocin in the interoceptive effects of 3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy') using a drug discrimination
      paradigm in the rat.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') use results in distinctive
      mood changes of a prosocial nature, most likely through its enhancement of
      serotonin (5HT) neurotransmission. Activation of 5HT-1A postsynaptic receptors
      has been shown to stimulate the release of oxytocin in the central nervous system
      where it regulates aspects of mood and behavior. Using a drug discrimination
      paradigm, we examined whether modulation of oxytocin receptor activity would
      affect conditioned behavioral responses to MDMA. Male and female Sprague Dawley
      rats (n=24) were trained to reliably differentiate between MDMA and a related
      stimulant, amphetamine (AMP), and saline using a three-lever drug discrimination
      paradigm. The extent to which substitution with carbetocin (an oxytocin analog)
      or co-administration with atosiban (an oxytocin receptor antagonist) affected
      drug-appropriate responding was evaluated. The tricyclic antidepressant
      imipramine was included as a negative control. The results supported the
      hypotheses that substitution with an oxytocin analog (carbetocin) would partially
      generalize to the MDMA training cue, whereas blocking oxytocin receptors with
      atosiban would result in a selective disruption of MDMA--but not AMP-appropriate
      responding. These findings were specific to the oxytocin receptor ligands as
      imipramine pre-treatment did not affect drug-appropriate responding. The results
      of this study implicate oxytocin receptor activation as a key MDMA-specific
      interoceptive cue in male and female rats and support the conclusion that this is
      one of the features of MDMA's subjective effects that distinguishes it from AMP.

PMID- 21070511
TI  - Human replicative DNA polymerase delta can bypass T-T (6-4) ultraviolet
      photoproducts on template strands.
AB  - DNA polymerase delta (Poldelta) carries out DNA replication with extremely high
      accuracy. This great fidelity primarily depends on the efficient exclusion of
      incorrect base pairs from the active site of the polymerase domain. In addition,
      the 3'-5' exonuclease activity of Poldelta further enhances its accuracy by
      eliminating misincorporated nucleotides. It is believed that these enzymatic
      properties also inhibit Poldelta from inserting nucleotides opposite damaged
      templates. To test this widely accepted idea, we examined in vitro DNA synthesis
      by human Poldelta enzymes proficient and deficient in the exonuclease activity.
      We chose the UV-induced lesions cyclobutyl pyrimidine dimer (CPD) and 6-4
      pyrimidone photoproduct (6-4 PP) as damaged templates. 6-4 PP represents the most
      formidable challenge to DNA replication, and no single eukaryotic DNA polymerase
      has been shown to bypass 6-4 PP in vitro. Unexpectedly, we found that Poldelta
      can perform DNA synthesis across both 6-4 PP and CPD even with a physiological
      concentration of deoxyribonucleotide triphosphates (dNTPs). DNA synthesis across
      6-4 PP was often accompanied by a nucleotide deletion and was highly mutagenic.
      This unexpected enzymatic property of Poldelta in the bypass of UV photoproducts
      challenges the received notion that the accuracy of Poldelta prevents bypassing
      damaged templates.

PMID- 21070512
TI  - Microbiological quality and antibiotic residues in informally marketed raw cow
      milk within the coastal savannah zone of Ghana.
AB  - OBJECTIVES: To investigate the microbiological quality and the presence of
      antibiotic residues in raw cow milk and in some indigenous milk products produced
      and marketed by the informal sector in the coastal savannah zone of Ghana.
      METHODS: Milk samples were aseptically collected from 224 kraals and samples of
      26 indigenous milk products were purchased from processors and retailers. Total
      plate counts, total coliform counts and the presence of Escherichia coli and E.
      coli O157:H7 were determined in all 250 samples. Milk samples were also tested
      for antibiotic residues. RESULTS: Total plate counts exceeded 105 CFU/ml in 45.2%
      of the samples while coliforms exceeded 103 CFU/ml in 66.0% and E. coli was
      detected in 11.2%. E. coli was present in raw cow milk but not in the indigenous
      products and all E. coli isolates were negative for E. coli O157:H7. Antibiotic
      residues were detected in 3.1% of the raw cow milk samples. CONCLUSION: Bulk milk
      contains unacceptable levels of hygiene indicators and antibiotic residues and is
      a potential source of milk-borne infections. The detection of E. coli and
      antibiotic residues raises public health concerns about the safety of fresh
      unpasteurized cow milk in the coastal savannah zone of Ghana and calls for
      improved farm hygiene, the need for milk pasteurization and the sensible use of
      antibiotics in the milk industry.

PMID- 21070513
TI  - Costs and outcomes of VCT delivery models in the context of scaling up services
      in Indonesia.
AB  - OBJECTIVE: To evaluate costs and outcomes of voluntary counselling and testing
      (VCT) service delivery models in urban Indonesia. METHODS: We collected primary
      data on utilization, costs and outcomes of VCT services in a hospital clinic (568
      clients), HIV community clinic (28 clients), sexually transmitted infection (STI)
      community clinic (784 clients) and prison clinic (574 clients) in Bandung,
      Indonesia, in the period January 2008-April 2009. RESULTS: The hospital clinic
      diagnosed the highest proportion and absolute number of HIV infections, but with
      the lowest average CD4 cell count and with the highest associated travelling and
      waiting time. The prison clinic detected fewer cases, but at an earlier stage,
      and all enrolled in HIV care. The community clinics detected the smallest number
      of cases, and only 0-8% enrolled in HIV care. The unit cost per VCT was highest
      in the hospital clinic (US$74), followed by the STI community clinic (US$65), the
      HIV community clinic (US$39) and the prison (US$23). CONCLUSION: We propose a
      reorientation of the delivery models for VCT and related HIV/AIDS treatment in
      this setting. We call for the scaling up of community clinics for VCT to improve
      access, promote earlier detection and to perform (early) treatment activities.
      This would reduce the burden of the hospital clinic to orient itself towards the
      treatment of AIDS patients. This is one of very few studies addressing this issue
      in Asia and the first of its kind in Indonesia, which has a rapidly growing HIV
      epidemic. The conceptual framework and overall conclusions may be relevant to
      other low-income settings.

PMID- 21070514
TI  - Quality of life of children with spina bifida in Kenya is not related to the
      degree of the spinal defects.
AB  - OBJECTIVES: To assess the relationship between the degree of symptoms and defects
      caused by spina bifida and the quality of life (QoL) of children with spina
      bifida in Kenya. METHODS: Children with spina bifida at BethanyKids at Kijabe
      Hospital, at mobile clinics throughout Kenya and a control group of healthy
      children were interviewed regarding their QoL. The SEIQoL-DW was used as an
      instrument to measure the QoL. This instrument can transfer well across cultures
      by using open questions clustered in six domains chosen based on the study group
      responses. Symptoms and impairment caused by spina bifida were obtained from the
      medical files. RESULTS: Sixty-nine per cent of 102 patients with spina bifida had
      a myelomeningocele, 59% had hydrocephalus, and of 49 incontinent children older
      than 2.5 years, 67% used clean intermittent catheterization. Quality of life of
      children was 65.1 on a scale from 0 to 100, compared to 78.0 in the healthy
      control group. Not one single determinant made a significant difference in the
      overall QoL. The most important domains were 'development' and 'self
      actualization'. The lowest scores were found in the domain 'health and disease'.
      CONCLUSION: This study showed no significant influence of the degree of defects
      of spina bifida on the QoL, but identified domains that can be targeted for
      improvement in children with spina bifida.

PMID- 21070515
TI  - Phylogenetic and proteomic analysis of an anaerobic toluene-degrading community.
AB  - AIMS: This study intended to unravel the physiological interplay in an anaerobic
      microbial community that degrades toluene under sulfate-reducing conditions
      combining proteomic and genetic techniques. METHODS AND RESULTS: An enriched
      toluene-degrading community (Zz5-7) growing in batch cultures was investigated by
      DNA- and protein-based analyses. The affiliation and diversity of the community
      were analysed using 16S ribosomal RNA (rRNA) genes as a phylogenetic marker as
      well as bssA and dsrAB genes as functional markers. Metaproteome analysis was
      carried out by a global protein extraction and a subsequent protein separation by
      two-dimensional gel electrophoresis (2-DE). About 85% of the proteins in the
      spots were identified by nano-liquid chromatography coupled with electrospray
      mass spectrometry (nano-LC-ESI-MS/MS) analysis. DNA sequencing of bssA and the
      most abundant dsrAB amplicons revealed high similarities to a member of the
      Desulfobulbaceae, which was also predominant according to 16S rRNA gene
      amplicons. Metaproteome analysis provided 202 unambiguous protein identifications
      derived from 236 unique protein spots. The proteins involved in anaerobic toluene
      activation, dissimilatory sulfate reduction, hydrogen production/consumption and
      autotrophic carbon fixation were mainly affiliated to members of the
      Desulfobulbaceae and several other Deltaproteobacteria. CONCLUSION: Phylogenetic
      and metaproteomic analyses revealed a member of the Desulfobulbaceae as the key
      player of anaerobic toluene degradation in a sulfate-reducing consortium.
      SIGNIFICANCE AND IMPACT OF THE STUDY:   This is the first study that combines
      genetic and proteomic analyses to indicate the interactions in an anaerobic
      toluene-degrading microbial consortium.

PMID- 21070516
TI  - A real-time qPCR assay for the detection of the nifH gene of Methanobrevibacter
      smithii, a potential indicator of sewage pollution.
AB  - AIMS: To develop a quantitative, real-time PCR assay to detect the nifH gene of
      Methanobrevibacter smithii. Methanobrevibacter smithii is a methanogenic archaea
      found in the intestinal tract of humans that may be a useful indicator of sewage
      pollution in water. METHODS AND RESULTS: Quantification standards were prepared
      from Meth. smithii genomic DNA dilutions, and a standard curve was used to
      quantify the target gene and calculate estimated genome equivalency units. A
      competitive internal positive control was designed and incorporated into the
      assay to assess inhibition in environmental extracts. Testing the assay against a
      panel of 23 closely related methanogen species demonstrated specificity of the
      assay for Meth. smithii. A set of 36 blind water samples was then used as a field
      test of the assay. The internal control identified varying levels of inhibition
      in 29 of 36 (81%) samples, and the Meth. smithii target was detected in all water
      samples with known sewage input. CONCLUSIONS: The quantitative PCR assay
      developed in this study is a sensitive and rapid method for the detection of the
      Meth. smithii nifH gene that includes an internal control to assess inhibition.
      Further research is required both to better evaluate host specificity of this
      assay and the correlation with human health risks. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This research is the first description of the development of a rapid and
      sensitive quantitative assay for a methanogenic archaeal indicator of sewage
      pollution.

PMID- 21070517
TI  - The effects of subinhibitory concentrations of costus oil on virulence factor
      production in Staphylococcus aureus.
AB  - AIM: To determine the antimicrobial activity of costus (Saussurea lappa) oil
      against Staphylococcus aureus, and to evaluate the influence of subinhibitory
      concentrations of costus oil on virulence-related exoprotein production in staph.
      aureus. METHODS AND RESULTS: Minimal inhibitory concentrations (MICs) were
      determined using a broth microdilution method, and the MICs of costus oil against
      32 Staph. aureus strains ranged from 0.15 to 0.6 MUl ml(-1) . The MIC(50) and
      MIC(90) were 0.3 and 0.6 MUl ml(-1) , respectively. Western blot, haemolytic,
      tumour necrosis factor (TNF) release and real-time RT-PCR assays were performed
      to evaluate the effects of subinhibitory concentrations of costus oil on
      virulence-associated exoprotein production in Staph. aureus. The data presented
      here show that costus oil dose dependently decreased the production of alpha
      toxin, toxic shock syndrome toxin 1 (TSST-1) and enterotoxins A and B in both
      methicillin-sensitive Staph. aureus (MSSA) and methicillin-resistant Staph.
      aureus (MRSA). CONCLUSION: Costus oil has potent antimicrobial activity against
      Staph. aureus, and the production of alpha-toxin, TSST-1 and enterotoxins A and B
      in Staph. aureus was decreased by costus oil. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The data suggest that costus oil may deserve further investigation for its
      potential therapeutic value in treating Staph. aureus infections. Furthermore,
      costus oil could be rationally applied in food products as a novel food
      preservative both to inhibit the growth of Staph. aureus and to repress the
      production of exotoxins, particularly staphylococcal enterotoxins.

PMID- 21070518
TI  - Induction of cytokine formation by human intestinal bacteria in gut epithelial
      cell lines.
AB  - AIMS: To investigate the effects of human gut micro-organisms on cytokine
      production by human intestinal cell lines. METHODS AND RESULTS: Quantitative real
      time PCR assays were developed to measure the production of pro-inflammatory (IL
      1alpha, IL-6, IL-18 and TNFalpha) and anti-inflammatory (TGF-beta1, TGF-beta2,
      TGF-beta3, IL-4 and IL-10) cytokines in HT-29 and Caco-2 cell lines. They were co
      cultured with a range of mucosal bacteria isolated from ulcerative colitis
      patients, together with lactobacilli and bifidobacteria obtained from healthy
      people. HT-29 cells were also co-cultured with Campylobacter jejuni,
      enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli and Salmonella
      typhimurium. The majority of commensal bacteria tested suppressed the expression
      of anti-inflammatory cytokine mRNA, increased IL-18, reduced IL-1alpha, and with
      the exception of nonpathogenic E. coli, reduced TNF-alpha. All overtly pathogenic
      species increased both pro-inflammatory and anti-inflammatory cytokine mRNA.
      CONCLUSION:   Commensal and pathogenic species induced fundamentally different
      cytokine responses in human intestinal epithelial cell lines. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Interactions between commensal bacteria tested in this study
      and the innate immune system were shown to be anti-inflammatory in nature, in
      contrast to the pathogenic organisms investigated. These data contribute towards
      our understanding of how potential probiotic species can be used to suppress the
      pro-inflammatory response in inflammatory bowel disease.

PMID- 21070519
TI  - Investigating harms in clinical trials - no easy task.

PMID- 21070521
TI  - Men's Health: more than just plumbing.

PMID- 21070520
TI  - Methods for evaluating novel biomarkers - a new paradigm.

PMID- 21070522
TI  - What men should know about the impact of physical activity on their health.

PMID- 21070523
TI  - What men should know about metabolic syndrome, adiposopathy and 'sick fat'.

PMID- 21070524
TI  - Benign prostatic hyperplasia and prostate cancer: an overview for primary care
      physicians.
AB  - Benign prostatic hyperplasia (BPH) and prostate cancer (CaP) are major sources of
      morbidity in older men. Management of these disorders has evolved considerably in
      recent years. This article provides a focused overview of BPH and CaP management
      aimed at primary care physicians. Current literature pertaining to BPH and CaP is
      reviewed and discussed. The management of BPH has been influenced by the adoption
      of effective medical therapies; nonetheless, surgical intervention remains a
      valid option for many men. This can be accomplished with well-established
      standards such as transurethral resection of the prostate or with minimally
      invasive techniques. Prostate cancer screening remains controversial despite the
      recent publication of two large clinical trials. Not all prostate cancers
      necessarily need to be treated. Robot-assisted prostatectomy is a new and
      increasingly utilised technique for CaP management, although open radical
      retropubic prostatectomy is the oncological reference standard. The ageing of the
      population of the developed world means that primary care physicians will see an
      increasing number of men with BPH and CaP. Close collaboration between primary
      care physicians and urologists offers the key to successful management of these
      disorders.

PMID- 21070525
TI  - Biology and natural history of prostate cancer and the role of chemoprevention.
AB  - Androgens not only play an important role in the development and function of the
      prostate but they are also intimately involved in the development and progression
      of prostate cancer (PCa). Within the prostate, testosterone is converted to the
      more potent androgen dihydrotestosterone (DHT) via the action of 5alpha-reductase
      enzymes. DHT is the primary prostatic androgen and promotes the growth and
      survival of normal, hyperplastic and malignant prostate tissues. Throughout the
      different stages of PCa [prostatic intraepithelial neoplasia (PIN), localised,
      recurrent, and metastatic] there is an increase in expression of 5alpha-reductase
      enzymes, particularly in localised high-grade carcinoma. Specifically inhibiting
      5alpha-reductase may reduce the production of DHT in the prostate while
      maintaining other endogenous hormone levels. Clinical studies have shown
      significant PCa risk reduction by blocking this pathway with 5alpha-reductase
      inhibitors (5ARIs). However, this comes at a risk, albeit low, with sexual side
      effects, gynaecomastia and cardiac failure. In addition, one study has shown a
      slight, but significant, risk of high-grade PCa. The currently available evidence
      does not support the routine use of 5alpha-reductase inhibitors to prevent PCa in
      the general population. It could, however, be considered as an individual option
      for high-risk or concerned patients with appropriate education from the
      prescribing provider.

PMID- 21070526
TI  - Erectile dysfunction and testosterone screening with prostate specific antigen
      screening at age 40: are these three gender specific determinants additive for
      overall men's heath and do they improve traditional non-gender specific
      determinants to lessen cardiovascular risk and all-cause mortality?
AB  - AIMS: Assess support for a recommendation to add screening for both erectile
      dysfunction (ED) and hypogonadism to the initial medical evaluation of young-to
      middle aged (>= 40 years of age) men in light of recent guidelines suggesting
      prostate-specific antigen screening occur at that age. METHODS: A search of
      literature published from 1998 to 2009 was performed. Search terms included: ED
      combined with coronary artery disease (CAD), metabolic syndrome and hypogonadism,
      hypogonadism and ED, hypogonadism, ED and mortality. Articles were evaluated
      according to the Center of Evidence-Based Medicine. RESULTS: Both retrospective
      and prospective evaluations have demonstrated a strong relationship between ED,
      established cardiovascular risk factors, CAD and the potential occurrence of
      cardiovascular events. Low testosterone levels are associated with ED. Low serum
      total testosterone is an independent risk factor for both metabolic syndrome and
      type 2 diabetes and all-cause mortality. CONCLUSION: Traditionally, ED and
      testosterone levels have been considered mainly, if not exclusively, in the
      context of sexual health. The results briefly summarised herein and other recent
      reviews suggest that ED and hypogonadism are signals of future all-cause
      mortality and overall health status and thus move these evaluations into the
      broader arena of public health. Screening for ED and hypogonadism provide 'gender
      specific determinants' to assess general metabolic and cardiovascular health
      risks in men. It is the opinion of the authors that this screening be performed
      in addition to the well-established non-gender-specific screening tests of
      lipids, blood pressure, obesity and serum glucose.

PMID- 21070527
TI  - What doctors need to know about sex.

PMID- 21070528
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a
      minimally invasive mediastinal staging tool for lung cancer but also a diagnostic
      tool for mediastinal lesions near the airway. After a brief historic rationale,
      this article reviews the indications for EBUS-TBNA, provides an overview of
      practical, training and financial issues; reviews the evidence comparing the
      mediastinal staging tools and briefly discusses potential future applications.
      EBUS-TBNA is most commonly used for staging non-small cell lung cancer (NSCLC),
      but is also used for diagnosis of unexplained mediastinal lymphadenopathy of
      other causes. For staging before radical treatment, many centres still perform
      mediastinoscopy and this should be done to confirm negative EBUS-TBNA results in
      this setting and when the pre-test clinical probability of lung cancer is high.
      EBUS-TBNA may be used in the future for staging when the mediastinal nodes are
      normal according to radiological staging and also in re-staging. EBUS-TBNA can be
      learned with appropriate training and mentorship; it offers numerous advantages
      over mediastinoscopy; and it is less invasive and can reduce costs by avoiding
      unnecessary mediastinoscopies in many cases.

PMID- 21070529
TI  - How does late nephrological co-management impact chronic kidney disease? - an
      observational study.
AB  - AIMS: To assess the impact of late referral (LR) for nephrological co-management
      compared with early referral (ER) on morbidity and mortality in chronic kidney
      disease (CKD) and to identify individual factors associated with higher mortality
      in LR, correcting for lead-time and immortal time bias. PATIENTS AND METHODS:
      Retrospective observational study comparing 46 LR patients with 103 ER patients.
      The quality of CKD management was assessed by measures to prevent CKD progression
      and to modify CKD complications and cardiovascular risk factors according to
      current guidelines. One-year mortality of LR and ER was compared and factors
      associated with mortality were identified. Analysis was performed with equivalent
      GFR (glomerular filtration rate) of ER and LR at baseline to correct for lead
      time and immortal time bias. RESULTS: Late referral was associated with inferior
      control of most risk factors for CKD progression, CKD complications and
      cardiovascular risk factors. In particular, glycaemic control, the use of
      angiotensin converting enzyme inhibitors and angiotensin-2-receptor blockers in
      diabetic nephropathy or proteinuria, the control of nutritional and volume status
      were inferior in LR. One-year mortality was significantly higher in LR (RR 5.9
      (95% CI 1.5-19.6); p < 0.01). Inadequate control of blood pressure, anaemia,
      volume status, malnutrition and emergency initial dialysis, but not LR itself
      were independently associated with mortality. CONCLUSIONS: Late referral was
      associated with a substantially lower survival after correction for lead-time and
      immortal time bias and with inferior control of most risk factors for CKD
      progression, complications and cardiovascular risk factors. CKD patients may
      particularly profit from adequate control of blood pressure, anaemia, nutritional
      and volume status, and avoidance of emergency initial dialysis as these factors
      may predominately contribute to survival.

PMID- 21070530
TI  - Comparison of modified preadmission glucose-lowering regimen with basal/bolus
      regimen for glucose control on outcome in general medicine wards.
AB  - BACKGROUND: It is undecided whether glucose control as advocated by the
      professional organisations and the glucose-lowering method by itself affects
      clinical outcome in patients with diabetes mellitus hospitalised in general
      medical wards. Our aim was to investigate whether a basal/bolus regimen and a
      modified prehospitalisation regimen have a different impact on the clinical
      diabetic patients in general medicine wards. METHODS: Glucose control of patients
      with diabetes hospitalised in two different wards of internal medicine was
      achieved according to their wards' policy: a modified preadmission regimen
      (conventional regime) or a basal/bolus regimen (intensive regime). Death and any
      adverse event were determined during hospitalisation and within 6 months after
      discharge to assess clinical outcome. RESULTS: Median fasting and daily glucose
      levels were similar in the conventional (n = 116) and intensive regime (n = 129)
      groups: 161 mg/dl (inter-quartile range: 138-201) and 176 mg/dl (152-215) vs. 155
      mg/dl (133-208) and 173 mg/dl (146-208) respectively. Clinical outcome was not
      affected by the treatment modality. In the subgroup of patients hospitalised with
      infection, the median fasting glucose was significantly lower in the
      interventional compared with the conventional regime: 141 and 172 mg/dl
      respectively (p = 0.041). However, tighter control was associated with a
      significantly higher incidence of adverse events within 6 months after discharge:
      48.9% and 21.4% respectively (p = 0.047). CONCLUSION: In general medicine wards,
      modified prehospital hypoglycaemic regimens and a basal/bolus insulin regimen
      achieve similar glucose control. The clinical outcome was not affected by the
      modality of glucose control.

PMID- 21070532
TI  - Treatment of tendinopathy: is there a role for autologous whole blood and
      platelet rich plasma injection?
AB  - BACKGROUND: Chronic tendinopathies are a common source of disability and can be
      recalcitrant to conservative measures, which once exhausted may necessitate
      operative intervention. Blood and platelets, in particular, are a rich source of
      factors necessary for tissue healing. Autologous blood injections (ABI) are
      thought to promote tendon healing, but have been explored clinically in only a
      few limited studies. However, recently they have attracted media attention in
      relation to the world of professional athletes and sports-related injuries.
      METHOD: We review the evidence base for this technique using the available
      literature on PubMed. CONCLUSION: Refractory chronic tendinopathy may be
      responsive to ABIs, but the data available to date are limited by quality and
      size of study, as well as length of follow up, and are currently insufficient to
      recommend this modality for routine clinical use.

PMID- 21070531
TI  - The procognitive effects of leptin in the brain and their clinical implications.
AB  - BACKGROUND: Leptin is a pleiotropic hormone produced mainly by the adipose
      tissue. Its most well-known effect is to regulate food intake and energy
      metabolism within the hypothalamus. More recently, several peripheral and extra
      hypothalamic effects have been described, expanding leptin's actions far beyond
      energy balance. AIMS: To review the extra-hypothalamic effects of leptin and
      their possible clinical implications. METHODS: We did a PubMed search using the
      terms "leptin" AND "brain" AND "neuron" AND "glial", and selected the most
      relevant articles. RESULTS: In extra-hypothalamic sites, leptin has remarkable
      effects on neurogenesis, axon growth, synaptogenesis, denditric morphology,
      development of oligodendroglial cells, neuron excitability, neuroprotection and
      regulation of beta-amyloid levels. Those effects have been shown to improve
      cognition and mood in animal models of depression and anxiety. In lean humans,
      leptin levels have been negatively correlated with the development of Alzheimer's
      disease. CONCLUSIONS: Leptin has extra-hypothalamic effects that may protect the
      brain against the development of mood and neurodegenerative disorders, such as
      Alzheimer's disease. Better understanding of those effects may lead to the
      development of potential leptin-based therapies against such conditions.

PMID- 21070533
TI  - Analysis of patient information leaflets provided by a district general hospital
      by the Flesch and Flesch-Kincaid method.
AB  - INTRODUCTION: Patient information leaflets (PILs) remain the most frequently used
      sources of medical information. There is a concern that the reading age of these
      leaflets may exceed patient comprehension, thus negating their beneficial effect.
      The 'Flesch Reading Ease' and the 'Flesch-Kincaid grade level' are established
      methods for providing reliable and reproducible scores of readability. METHOD:
      All available hospital PILs (171) were assessed and divided into 21 departments.
      Microsoft Word was used to provide Flesch and Flesch-Kincaid readability
      statistics and compared against the national reading age and the recommended
      level for provision of medical information. RESULTS: The average Flesch
      readability of all of the hospital's PILs is 60, with a Flesch-Kincaid grade of
      7.8 (12-13 years old). There is considerable variation in the average readability
      between departments (Flesch readability 43.8-76.9, Flesch-Kincaid 5.4-10.2). The
      average scores of two departments have PILs scores suitable for patient
      information. CONCLUSION: Although our PILs were well laid out and easy to read,
      the majority would have exceeded patient comprehension. The current advice for
      provision of NHS information does not highlight the importance of a recommended
      reading level when designing a PIL. Potentially a wide group of patients are
      being excluded from the benefits of a PIL.

PMID- 21070534
TI  - Prevalence and outcome of litigation claims in England after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Approximately, 50,000 cholecystectomies are performed annually in the
      United Kingdom resulting in a number of negligence claims referred to the NHS
      Litigation Authority (NHSLA). The aim of this study was to assess the prevalence
      and outcomes of claims reported to the NHSLA after laparoscopic cholecystectomy
      performed in England between 1995 and 2008. METHODS: Data were requested from the
      NHSLA on all claims related to laparoscopic cholecystectomy which occurred in
      England between 1995 and 2008. RESULTS: A review of the data provided by the
      NHSLA data identified over 300 claims in this time period. Of the claims
      identified, 244 have been completed. Common bile duct injury (41%), bile leak
      (12%), bowel injury (9%), haemorrhage (9%) and fatality (9%) were the most
      frequent types of claim. Common bile duct injury resulted in the highest
      proportion of successful claims (86%) and the largest sums paid to the claimant
      (average L65,000). DISCUSSION: Common bile duct injury is the most common claim
      to the NHSLA after laparoscopic cholecystectomy and results in the highest
      proportion of successful claims and the largest sums paid to the claimant.

PMID- 21070535
TI  - Evidence-based flying taking off: maximising the effectiveness of a novel airline
      user decision-making tool.

PMID- 21070536
TI  - Management of hepatitis B: Consensus of the Japan Society of Hepatology 2009.
AB  - Recently, much progress has been made in the field of hepatitis B, such as
      natural history of the disease in relation to the amount of hepatitis B virus
      (HBV) DNA, genotypes of HBV influencing the natural course and treatment effects,
      mutations of HBV influencing the severity of the disease and development of
      hepatocellular carcinoma, and antiviral treatment such as nucleos(t)ide analogues
      and pegylated interferon. To make the consensus for the diagnosis, management and
      treatment of hepatitis B, a meeting was held during 45th annual meeting of Japan
      Society of Hepatology (JSH) in June 2009. In the meeting, recommendations and
      informative statements were discussed on the following subjects: (i) natural
      history of HBV infection; (ii) clinical implication of HBV genotypes; (iii) HBV
      mutations and their potential impact on pathogenesis of HBV infection; (iv)
      indications for antiviral treatment of chronic hepatitis B; (v) nucleos(t)ide
      analogues for chronic hepatitis B; and (vi) interferon therapy for chronic
      hepatitis B. The presenters reviewed the data on these subjects and proposed the
      consensus statements and recommendations. These statements were discussed among
      the organizers and presenters, and were approved by the participants of the
      meeting. In the current report, the relevant data were reviewed and the 12
      consensus statements and nine recommendations on chronic hepatitis B were
      described.

PMID- 21070537
TI  - Diversity of antiviral-resistant human cytomegalovirus in heart and lung
      transplant recipients.
AB  - Immunocompromised transplant recipients are at high risk for human
      cytomegalovirus (CMV)-related infection and disease. Antiviral prophylaxis and
      treatment have reduced CMV morbidity and mortality, but at times promote
      development of antiviral-resistant CMV strains that can significantly contribute
      to adverse clinical outcomes in transplant recipients. We have investigated CMV
      genotypes in transplant recipients (bone marrow, stem cell, kidney, heart, lung,
      and liver) receiving antiviral prophylaxis or preemptive therapy or treatment, to
      determine the viral characteristics and clinical impact of antiviral-resistant
      CMV in these different groups. Antiviral-resistant CMV strains were detected by
      polymerase chain reaction sequencing of the CMV protein kinase (UL97) and viral
      DNA polymerase (UL54) genes from clinical specimens. A trend toward more frequent
      detection of multidrug resistance and co-circulation of multiple resistant
      strains was seen in heart and lung transplant recipients compared with other
      transplantation types. A greater diversity and number of UL97 and UL54 mutations
      were observed in heart and lung transplant recipients; whereas antiviral
      resistant CMV infections in other transplant recipients were predominantly the
      result of a single mutant genotype. Furthermore, 43% (6/14) of CMV-positive heart
      and lung transplant recipients were infected with CMV strains containing UL54
      mutations conferring multidrug resistance compared with only 6% (1/18) of CMV
      positive recipients of other transplanted organs or stem cells. Emergence of CMV
      strains containing previously unrecognized UL54 mutations (F412S and D485N) also
      occurred in 1 lung and 1 heart transplant recipient. The development of these
      mutations under antiviral selective pressure, and clinical outcome of infection
      suggests these mutations are likely to confer antiviral resistance. Emergence of
      CMV antiviral resistance remains a significant issue in immunocompromised
      patients treated with antiviral agents, and emphasizes the relevance of regular
      antiviral resistance testing when designing optimal patient-management
      strategies.

PMID- 21070540
TI  - Intraoperative mydriasis by intracameral injection of mydriatic eye drops: in
      vivo efficacy and in vitro safety studies.
AB  - BACKGROUND: This study investigated the efficacy and safety of intracameral
      injection of commercially available eye drops containing 0.5% tropicamide and
      0.5% phenylephrine hydrochloride (Mydrin-P, Santen Pharmaceutical, Osaka, Japan).
      DESIGN: In vitro experiment and prospective clinical study at a private hospital.
      PARTICIPANTS AND SAMPLES: Mydrin-P was applied to confluent cultured human
      corneal endothelial cells, and the cellular morphology was examined. Clinical
      study subjects were 65 eyes of 65 patients that underwent phaco-emulsification
      and aspiration with intraocular lens implantation and received intracameral
      injection of Mydrin-P for poor mydriasis after preoperative topical instillation
      of mydriatics (intraocular mydriasis group; with five subgroups based on cause:
      diabetes, pseudo-exfoliation, post-surgery, uveitis, unknown). Controls,
      comprising 39 eyes of 39 patients, were not injected with Mydrin-P. METHODS: The
      ratio of pupillary diameter to corneal diameter was determined before and after
      injection of Mydrin-P. Corneal endothelial density was measured preoperatively
      and 3 months and 1 year postoperatively. MAIN OUTCOME MEASURES: Pupillary
      diameter and corneal endothelial density. RESULTS: Human corneal endothelial cell
      morphology was unaltered after Mydrin-P injection. The mean ratio of the
      pupillary diameter to corneal diameter increased in the intraocular mydriasis
      group (before: 54.2 +/- 4.8%, after: 58.4 +/- 6.6%; P < 0.001) and in the
      diabetes and unknown subgroups. The corneal endothelial cell density reduction
      rate 3 months and 1 year after surgery was not significantly different between
      the intraocular mydriasis group and controls. CONCLUSION: Intracameral injection
      of Mydrin-P appears to be effective and safe for dilating the pupil in cases with
      poor mydriasis after preoperative instillation of mydriatics.

PMID- 21070542
TI  - Keratoconus in Asians: demographics, clinical characteristics and visual function
      in a hospital-based population.
AB  - BACKGROUND: To describe the demographics, clinical characteristics and visual
      function of Asian patients with keratoconus managed in a tertiary eye centre.
      DESIGN: Prospective cross-sectional study. PARTICIPANTS: 116 patients with
      clinically evident or suspected keratoconus (on videokeratography) recruited over
      11 months. METHODS: A standardised interview, full ophthalmic examination,
      refraction and corneal topography were performed. Visual function was assessed
      with the VF-14 questionnaire. MAIN OUTCOME MEASURES: Demographics, clinical
      characteristics and visual function. RESULTS: Mean age of our patients was 29.5
      +/- 9.40 years on enrolment, 62.9% were male, and the ethnic distribution was
      60.3% Chinese, 13.8% Malays and 9.5% Indians. Clinically evident keratoconus was
      present bilaterally in 65 patients (56.0%) and unilateral keratoconus in five
      patients (4.3%). Five patients (4.3%) had a family history of keratoconus. The
      majority of patients were managed with contact lenses (60.8%) or glasses (24.5%).
      Eye rubbing was common (68%) as were asthma (26.3%) and eczema (18.4%). Conical
      protrusion was the commonest sign (75.3%). The mean cylinder was higher in
      keratoconus eyes compared with keratoconus suspect eyes (-4.01 vs. -1.27, P <
      0.001), and best-corrected visual acuity was poorer (0.19 vs. 0.05, P < 0.001).
      Unaided visual acuity was significantly worse with increasing age (P = 0.016). On
      the VF-14, 32% scored 90 or less (out of 100), reflecting difficulties with
      vision-related daily activities. CONCLUSIONS: Our Asian patients with keratoconus
      had similar demographic and clinical characteristics to patients in Western
      populations. Even with apparently good visual acuity, some patients still
      experience substantial impairment in vision-related activities.

PMID- 21070541
TI  - Anti-adenoviral effect of interferon-beta and interferon-gamma in serotypes that
      cause acute keratoconjunctivitis.
AB  - BACKGROUND: Interferons are currently used for hepatitis B and C virus infection;
      the effect of interferons against adenovirus has not been elucidated. It has been
      reported that interferon-beta and interferon-gamma were effective against
      adenovirus serotype 3. We investigated the anti-adenoviral effect of interferon
      beta and interferon-gamma in serotypes that cause acute keratoconjunctivitis,
      using quantitative polymerase chain reaction in vitro. DESIGN: Experimental study
      carried out in a university. SAMPLES: Five strains of different serotypes of
      adenovirus, types 3 (AdV3; species B), 4 (species E), 8, 19a and 37 (species D)
      and interferon-beta and interferon-gamma for in vitro assay. METHODS: After
      pretreatment of A549 with serial dilution of interferons for 24 h, adenovirus was
      cultivated for 7 days, and adenoviral DNA was quantitatively measured by real
      time polymerase chain reaction. MAIN OUTCOME MEASURES: Number of virus copies
      after treatment and the 50% effective concentration (EC(50) ). RESULTS:
      Interferon-beta showed a dose-dependent inhibitory effect on all serotypes.
      EC(50) of interferon-beta ranged between 211 and 843 IU/mL. A similar tendency
      was observed with interferon-gamma. EC(50) of interferon-gamma ranged between 133
      and 9130 IU/mL. Among the serotypes, interferon-gamma exhibited the greatest
      inhibitory effect on AdV37. In contrast, AdV4 showed the lowest sensitivity to
      interferon-gamma. Statistically significant dose dependency for both interferon
      beta and interferon-gamma was observed in several serotypes. CONCLUSIONS: These
      results suggest that both interferon-beta and interferon-gamma have anti
      adenoviral activity in vitro. Interferons have the potential to be used for local
      treatment of adenoviral keratoconjunctivitis, although further evaluation in
      animal models and clinical trials is necessary.

PMID- 21070543
TI  - Cystic change within a dermolipoma.

PMID- 21070544
TI  - Comparison of the influence of cataract and pupil size on retinal nerve fibre
      layer thickness measurements with time-domain and spectral-domain optical
      coherence tomography.
AB  - BACKGROUND: To investigate and compare the effect of cataract and pupil size on
      retinal nerve fibre layer (RNFL) thickness measurements using spectral-domain
      optical coherence tomography (Cirrus OCT) and time-domain OCT (Stratus OCT).
      DESIGN:   Prospective, hospital-based study. PARTICIPANTS: Twenty-five eyes from
      25 normal subjects undergoing cataract surgery. METHODS:   Three retinal nerve
      fibre layer (RNFL) thickness measurements were taken before and after dilation,
      preoperatively and postoperatively, using Cirrus 200*200 Optic Disc Scan and
      Stratus Fast RNFL Scan. MAIN OUTCOME MEASURES:  Linear regression, intraclass
      correlation coefficient (ICC) and coefficient of variation analysis. RESULTS:
      Cataract removal caused significant increase in RNFL measurements in both
      modalities (Cirrus P<0.02; Stratus P<0.001). There was no significant difference
      in the increase in measurements between the two machines. Pupil dilation had
      variable and non-statistically significant effect in both (P>0.05). ICC showed
      excellent reproducibility with Cirrus OCT after mydriasis, preoperatively
      (ICC=0.78-0.90) and postoperatively (ICC=0.90-0.97), but poor reproducibility
      before mydriasis (P<0.75). Stratus OCT achieved excellent reproducibility after
      cataract removal both before (ICC=0.86-0.96) and after mydriasis (ICC=0.92-0.95),
      but poor reproducibility before cataract surgery (P<0.75). CONCLUSIONS:
      Cataracts, not pupil size, cause significant underestimation of RNFL measurements
      in both Cirrus and Stratus OCT. The extent of influence exerted does not appear
      different between the two instruments. Reproducibility of each machine appears to
      be affected differently. Mydriasis is required to achieve excellent
      reproducibility with Cirrus OCT, and media clarity is required with Stratus OCT.

PMID- 21070545
TI  - Descemet-stripping automated endothelial keratoplasty: a successful alternative
      to repeat penetrating keratoplasty.
AB  - BACKGROUND:   Although Descemet-stripping automated endothelial keratoplasty has
      replaced penetrating keratoplasty for primary treatment of endothelial disorders,
      many patients have already undergone penetrating keratoplasty. It is unclear when
      repeat penetrating keratoplasty is necessary or when endothelial keratoplasty may
      restore clarity to a failed graft. DESIGN:   Retrospective case series of
      patients undergoing Descemet-stripping automated endothelial keratoplasty after
      penetrating keratoplasty by three surgeons at an academic tertiary care centre.
      PARTICIPANTS:   Eight patients with Descemet-stripping automated endothelial
      keratoplasty after penetrating keratoplasty from 2006 to 2009. METHODS:  
      Microkeratome-prepared Descemet-stripping automated endothelial keratoplasty
      donor tissue was used. In seven cases, the penetrating keratoplasty bed was
      neither stripped nor scraped, and in one, scraping only was performed. MAIN
      OUTCOME MEASURES:   Preoperative and 6-month postoperative best-corrected visual
      acuities in logMAR (logarithm of the minimum angle of resolution). RESULTS:   The
      average pre-Descemet-stripping automated endothelial keratoplasty best-corrected
      visual acuity was 1.375, and the average best-corrected visual acuity 6months
      postoperatively was logMAR 1.0, a 2.5-fold improvement in the minimum angle of
      resolution (P=0.22). Seven of the eight patients showed an improvement in best
      corrected visual acuity, and one patient had failure of Descemet-stripping
      automated endothelial keratoplasty and required penetrating keratoplasty. Five
      had a postoperative event: one had a gap that resolved spontaneously, three
      required rebubblings (injections of air only without otherwise repositioning the
      graft), and one experienced graft failure. CONCLUSIONS:   Descemet-stripping
      automated endothelial keratoplasty can successfully rescue a prior penetrating
      keratoplasty, even with a fairly high detachment rate. Given these favourable
      visual outcomes, further study of this promising strategy is justified.

PMID- 21070546
TI  - Glaucomatous optic neuropathy evaluation project: a standardized internet system
      for assessing skills in optic disc examination.
AB  - BACKGROUND: Development of a standardized internet-based system to self-assess
      skills in optic disc examination for glaucoma risk assessment. DESIGN:
      Prospective internet-based observational study. PARTICIPANTS: Total of 197
      participants (glaucoma subspecialists, general ophthalmologists and trainees)
      from 22 countries. METHODS: Forty-two optic disc images demonstrating a range of
      features were selected from 2500 monoscopic disc photographs of normal and
      glaucomatous eyes. Images were presented to clinicians via website
      (http://www.gone-project.com). Participants were asked to assess nine topographic
      features and make a subjective assessment of glaucoma likelihood. MAIN OUTCOME
      MEASURES: Inter-observer agreement using kappa (kappa) or weighted kappa
      (kappa(w) ). RESULTS: There was substantial level of inter-observer agreement
      between glaucoma subspecialists for assessment of glaucoma likelihood (kappa(w) =
      0.63). Inter-observer agreement was high for haemorrhage (kappa= 0.83) and
      substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and
      cup shape (kappa(w) = 0.59-0.68). Subspecialists had stronger inter-observer
      agreement for glaucoma likelihood and for most disc characteristics than did
      trainees: the greatest difference being the assessment for retinal nerve fibre
      layer loss. Analysis of individual disc answers from ophthalmology trainees
      showed that discs leading to lower agreement of glaucoma likelihood tend to
      produce lower agreement for the assessment of cup:disc ratio, cup shape, cup
      depth and retinal nerve fibre layer. Discs with features of moderate to deep cup
      or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma
      likelihood. CONCLUSIONS: This internet-based system is a readily accessible and
      standardized tool, for clinicians globally, that permits self-assessment and
      benchmarking of skills in optic disc examination.

PMID- 21070547
TI  - Plasma and aqueous humour levels of ghrelin in open-angle glaucoma patients.
AB  - BACKGROUND: To compare aqueous humour and plasma levels of ghrelin, a peptide
      recently identified in human eyes, in patients with open-angle glaucoma and
      controls. DESIGN: Cross-sectional, controlled, hospital-based study.
      PARTICIPANTS: Twenty-four open-angle glaucoma (17 primary open-angle and 7 pseudo
      exfoliation glaucoma) patients and 30 controls were included. All participants
      were patients scheduled for cataract or glaucoma surgery. Patients with other
      ocular pathology, previous ocular surgery or diabetes were excluded. METHODS:
      Blood samples were collected before elective surgery. Aqueous humour was
      aspirated from the anterior chamber through a paracentesis with a 27-G needle
      under sterile conditions before any tissue manipulation. Ghrelin quantification
      was performed with commercially available Radioimmunoassay kits. MAIN OUTCOME
      MEASURE: Ghrelin levels in aqueous humour and plasma. RESULTS: Plasma levels of
      ghrelin were 490.5 +/- 156.0 pg/mL in the open-angle glaucoma and 482.2 +/- 125.4
      pg/mL in the control group (Mann-Whitney test, P = 0.897). Aqueous humour levels
      of ghrelin were 85.5 +/- 15.4 and 123.4 +/- 25.5 pg/mL in the respective groups
      (P < 0.001). The ratio of plasma/aqueous humour ghrelin concentration was higher
      in the open-angle glaucoma versus the control group (5.75 +/- 1.92 vs. 4.00 +/-
      1.04, P < 0.001). There was no difference in aqueous humour levels of ghrelin
      between primary open-angle glaucoma and pseudo-exfoliation glaucoma patients (P =
      0.494). CONCLUSIONS: Aqueous humour levels of ghrelin were significantly lower in
      open-angle glaucoma patients, compared with controls. This difference may
      manifest a role of ghrelin in the disease process or a consequence of
      antiglaucoma treatment.

PMID- 21070548
TI  - Conductive keratoplasty for symptomatic presbyopia following monofocal
      intraocular lens implantation.
AB  - BACKGROUND: To evaluate the visual outcomes of conductive keratoplasty for relief
      of symptomatic presbyopia of pseudophakia with monofocal intraocular lens
      implantation. DESIGN: It was a prospective clinical study and set in Eye Center,
      Second Affiliated Hospital, Zhejiang University. PARTICIPANTS: This study
      comprised 27 eyes from 27 patients with presbyopia symptom. METHODS: The patients
      received conductive keratoplasty via monovision approach after monofocal
      intraocular lens implantation and were followed up at 1 week and 1, 3, 6 and 12
      months postoperatively. MAIN OUTCOME MEASURES: The main outcomes including
      uncorrected near visual acuity, uncorrected distance visual acuity, best
      spectacle-corrected visual acuity, manifest refraction spherical equivalent,
      keratometric astigmatism, contrast and glare sensitivity, spherical aberration
      and pseudoaccommodation were evaluated. RESULTS: Twelve months after conductive
      keratoplasty, the binocular uncorrected near visual acuity was significantly
      improved from logMAR 0.88 +/- 0.16 preoperatively to logMAR 0.30 +/- 0.13 (P <
      0.05); the binocular uncorrected distance visual acuity and best spectacle
      corrected visual acuity remained unchanged; manifest refraction spherical
      equivalent was significantly reduced from 0.01 +/- 0.68 D preoperatively to -1.68
      +/- 0.39 D (P < 0.05); spherical aberration was increased from 0.266 +/- 0.204 um
      preoperatively to 0.358 +/- 0.277 um (P < 0.05), and pseudoaccommodation was from
      1.38 +/- 0.38 D to 1.73 +/- 0.61 D (P < 0.05). CONCLUSIONS: Conductive
      keratoplasty is a safe and effective method for relief of symptomatic presbyopia
      of pseudophakia with monofocal intraocular lens implantation.

PMID- 21070549
TI  - Endoscopic transorbital approach for repair of cerebrospinal fluid leakage
      following removal of an orbito-cranial foreign body.

PMID- 21070550
TI  - Quality of life of the most severely vision-impaired.
AB  - BACKGROUND: To explore the interaction between vision impairment, perceived
      quality of life loss and willingness to trade remaining life for vision gain.
      DESIGN: Community-based cross-sectional study. PARTICIPANTS: Legally blind or
      severely vision-impaired people selected randomly from the Association for the
      Blind of Western Australia register. METHODS: Individuals were examined by
      consultant ophthalmologists and completed the Impact of Vision Impairment profile
      quality of life assessment and a Time Trade-Off evaluation. Vision-related
      utility values were calculated. The results were analysed using univariate and
      multivariate regression methods. MAIN OUTCOME MEASURES: IVI Rasch Logits and TTO
      utility values (TTO UV). RESULTS: 156 people volunteered to contribute to the
      study. The median age was 80 (19-97) years, and 56% were female. Being legally
      blind (logMAR > 1) (95% CI 1.1 to 5.2, P = 0.003), clinically depressed (95% CI 
      11.2 to -1.8, P = 0.007) or more than 40 years of age (95% CI 0.9 to 8.1, P =
      0.015) significantly lowered overall impact of vision impairment scores. The
      emotional domain of impact of vision impairment was associated with willingness
      to trade part of remaining life. A 5-Logit increase in impact of vision
      impairment emotional score resulted in a 21% (95% CI 10 to 31) decrease in the
      odds of being likely to trade life for sight. The Australian definition of
      blindness compared with World Health Organisation or USA best separates those
      with perceived loss and appears useful in identifying vision loss-related
      morbidity. CONCLUSIONS: These results suggest that emotional health and lack of
      depression are important determinants for quality and value of life.

PMID- 21070551
TI  - Severe intraocular trauma in a fireman caused by a high-pressure water jet.

PMID- 21070552
TI  - Vision screening of children attending primary school in rural Timor-Leste.

PMID- 21070553
TI  - Is sekentei associated with attitudes toward use of care services?: multilevel
      analysis in Japan.
AB  - AIM: To examine the relationship between individual and regional levels of
      sekentei and attitudes toward care services in the general Japanese population.
      METHODS: A cross-sectional survey was conducted in January and February 2005
      using a mailed-in self-administered questionnaire. Participants were 4735
      community residents aged 20-75 years living in 23 regions in the city of Koka in
      Shiga Prefecture. Questions encompassed demographic data, attitudes toward the
      use of formal care services and the Sekentei Scale. The regional variable of
      sekentei was constructed by aggregating the individual sekentei scores within
      elementary school districts. Multilevel logistic regression analysis was
      conducted to assess the association between individual and regional sekentei and
      attitudes toward care services. RESULTS: A total of 2264 questionnaires were
      analyzed. Approximately 16% of respondents were willing to use formal care
      services. Multilevel analysis showed that lower individual sekentei was
      associated with the willingness to use formal care services among both men and
      women (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.93-0.99 in men;
      OR = 0.96, 95% CI = 0.92-1.00 in women). Among men, the negative association
      between regional sekentei and the willingness to use formal care services was
      marginally significant (OR = 0.69, 95% CI = 0.48-1.01) as was the interaction
      between individual and regional sekentei levels. CONCLUSION: These results
      indicate the importance of assessing not only the individual sekentei level but
      also the sekentei level in different regions to develop strategies for the
      allocation of care resources.

PMID- 21070554
TI  - How do plant ecologists use matrix population models?
AB  - Matrix projection models are among the most widely used tools in plant ecology.
      However, the way in which plant ecologists use and interpret these models differs
      from the way in which they are presented in the broader academic literature. In
      contrast to calls from earlier reviews, most studies of plant populations are
      based on < 5 matrices and present simple metrics such as deterministic population
      growth rates. However, plant ecologists also cautioned against literal
      interpretation of model predictions. Although academic studies have emphasized
      testing quantitative model predictions, such forecasts are not the way in which
      plant ecologists find matrix models to be most useful. Improving forecasting
      ability would necessitate increased model complexity and longer studies.
      Therefore, in addition to longer term studies with better links to environmental
      drivers, priorities for research include critically evaluating
      relative/comparative uses of matrix models and asking how we can use many short
      term studies to understand long-term population dynamics.

PMID- 21070555
TI  - A guide to the genomics of ecological speciation in natural animal populations.
AB  - Interest in ecological speciation is growing, as evidence accumulates showing
      that natural selection can lead to rapid divergence between subpopulations.
      However, whether and how ecological divergence can lead to the buildup of
      reproductive isolation remains under debate. What is the relative importance of
      natural selection vs. neutral processes? How does adaptation generate
      reproductive isolation? Can ecological speciation occur despite homogenizing gene
      flow? These questions can be addressed using genomic approaches, and with the
      rapid development of genomic technology, will become more answerable in studies
      of wild populations than ever before. In this article, we identify open questions
      in ecological speciation theory and suggest useful genomic methods for addressing
      these questions in natural animal populations. We aim to provide a practical
      guide for ecologists interested in incorporating genomic methods into their
      research programs. An increased integration between ecological research and
      genomics has the potential to shed novel light on the origin of species.

PMID- 21070556
TI  - Barium imaging of the small bowel in Crohn's disease.

PMID- 21070559
TI  - Plant diversity and the stability of foodwebs.
AB  - Insect outbreaks in forest and agriculture monocultures led Charles Elton to
      propose, a half-century ago, that higher plant diversity stabilized animal
      foodweb dynamics in natural ecosystems. We tested this hypothesis by studying
      arthropod community dynamics in a long-term experimental manipulation of
      grassland plant species diversity. Over the course of a decade, we found that
      higher plant diversity increased the stability (i.e. lowered year-to-year
      variability) of a diverse (>700 species) arthropod community across trophic
      levels. As the number of plant species increased, the stability of both herbivore
      and predator species richness and of total herbivore abundance increased. The
      underlying mechanisms driving these diversity-stability relationships were plant
      diversity, via effects on primary productivity and plant community stability, and
      portfolio effects. Taken together, our results show that higher plant diversity
      provides more temporally consistent food and habitat resources to arthropod
      foodwebs. Consequently, actively managing for high plant diversity may have
      stronger than expected benefits for increasing animal diversity and controlling
      pest outbreaks.

PMID- 21070560
TI  - Driven to distraction: detecting the hidden costs of flea parasitism through
      foraging behaviour in gerbils.
AB  - Gerbilline rodents such as Allenby's gerbils (Gerbillus andersoni allenbyi), when
      parasitized by fleas such as Synosternus cleopatrae pyramidis, devote long hours
      of grooming to remove the ectoparasites. Yet no detrimental energetic or
      immunological effects of the ectoparasites have been found in adult Allenby's
      gerbil. Why should gerbils go to such trouble? We tested for the various ways
      that fleas can negatively affect gerbils by manipulating flea infestation on
      gerbils and the presence of a fox. We demonstrate that gerbils responded to fleas
      by leaving resource patches at higher giving-up densities. Furthermore, they
      stayed in those resource patches less time and left them at higher quitting
      harvest rates so long as a fox was also present. When flea-ridden, gerbils also
      abandoned using vigilance to manage risk and relied mainly on time allocation.
      Thus, having fleas imposed a foraging cost similar in nature to that arising from
      the risk of predation from foxes and may be even larger in magnitude. More than
      that, the presence of fleas acted as a magnifier of foraging costs, especially
      those arising from the risk of predation. The fleas reduced the gerbils' foraging
      aptitude and altered how they went about managing risk of predation. We
      hypothesize that fleas reduce the attention that gerbils otherwise have for
      foraging and predator detection. We suggest that this is the major cost of
      ectoparasitism.

PMID- 21070561
TI  - Temporal change in the diversity-invasibility relationship in the presence of a
      disturbance regime.
AB  - Disturbance can affect both the diversity and invasibility of communities. Many
      field studies have found correlations between diversity and susceptibility to
      invasion, but if both factors independently respond to disturbance then spurious
      non-causal relationships may be observed. Here, we show that disturbance can
      cause a temporal shift in the diversity-invasibility relationship. In a field
      experiment using sessile marine communities, disturbance strongly affected both
      diversity and invasion such that they were highly correlated. Disturbance
      facilitated initial invasion, creating a negative diversity-invasibility
      relationship when the invader first arrived. Over time, disturbance hindered the
      persistence of invaders, creating a positive diversity-invasibility relationship.
      We suggest that temporal changes in the diversity-invasibility relationship may
      have contributed to the 'invasion paradox', a term for the contrasting patterns
      of experimental and observational studies of the diversity-invasibility
      relationship.

PMID- 21070563
TI  - Robust scaling in ecosystems and the meltdown of patch size distributions before
      extinction.
AB  - Robust critical systems are characterized by power laws which occur over a broad
      range of conditions. Their robust behaviour has been explained by local
      interactions. While such systems could be widespread in nature, their properties
      are not well understood. Here, we study three robust critical ecosystem models
      and a null model that lacks spatial interactions. In all these models,
      individuals aggregate in patches whose size distributions follow power laws which
      melt down under increasing external stress. We propose that this power-law decay
      associated with the connectivity of the system can be used to evaluate the level
      of stress exerted on the ecosystem. We identify several indicators along the
      transition to extinction. These indicators give us a relative measure of the
      distance to extinction, and have therefore potential application to conservation
      biology, especially for ecosystems with self-organization and critical
      transitions.

PMID- 21070562
TI  - Navigating the multiple meanings of beta diversity: a roadmap for the practicing
      ecologist.
AB  - A recent increase in studies of beta diversity has yielded a confusing array of
      concepts, measures and methods. Here, we provide a roadmap of the most widely
      used and ecologically relevant approaches for analysis through a series of
      mission statements. We distinguish two types of beta diversity: directional
      turnover along a gradient vs. non-directional variation. Different measures
      emphasize different properties of ecological data. Such properties include the
      degree of emphasis on presence/absence vs. relative abundance information and the
      inclusion vs. exclusion of joint absences. Judicious use of multiple measures in
      concert can uncover the underlying nature of patterns in beta diversity for a
      given dataset. A case study of Indonesian coral assemblages shows the utility of
      a multi-faceted approach. We advocate careful consideration of relevant
      questions, matched by appropriate analyses. The rigorous application of null
      models will also help to reveal potential processes driving observed patterns in
      beta diversity.

PMID- 21070564
TI  - Environmental variability can select for optimism or pessimism.
AB  - We propose operational definitions of reproductive optimism and pessimism;
      optimism involves behaving in a way that gives too much weight (in terms of
      producing surviving offspring) to positive events, pessimism gives too much
      weight to negative events. Natural selection maximizes the long-term growth of a
      lineage rather than short-term measures such as numbers of offspring.
      Consequently, optimism or pessimism can be favoured by natural selection, even
      though such biases appear irrational from a short-term perspective. We
      investigate the evolution of optimism in a metapopulation. The circumstances of a
      patch change over time, independently of other patches. With sufficient dispersal
      between patches, stochasticity affects members of a lineage largely independently
      and optimism is favoured. With little dispersal, the temporal fluctuations of a
      patch affect many members similarly; pessimism is then favoured. Our results
      establish that the spatial and temporal structure of the environment is crucial
      in determining the direction of evolved biases.

PMID- 21070565
TI  - Lymphogranuloma venerum (LGV) proctitis mimicking rectal cancer.

PMID- 21070566
TI  - Transanal repair for treatment of rectocele in obstructed defaecation: manual or
      stapled.
AB  - AIM: Our aim is to evaluate the results of transanal repair of rectocele, either
      manual or stapled, considering the anatomic, manometric and symptomatic
      improvement. METHODS: Forty-five female patients with obstructed defaecation due
      to anterior rectocele were operated on in the Colorectal Surgery Unit, Mansoura
      University Hospital, after history taking, detailed questionnaire analysis,
      barium enema, anorectal manometric studies, EMG studies, anal endosonography,
      balloon expulsion test, colonic transit time and defaecographic studies.
      Transanal manual repair was performed for 23 patients (group 1), and transanal
      stapled repair (group 2) was performed for 22 patients. Postoperative
      complications were recorded, and the patients were followed up for 1 year.
      Functional results were evaluated at 3, 6 and 12 months after surgery by
      questionnaire, anorectal manometry and evacuation proctography. RESULTS: Time of
      operation and hospital stay were significantly shorter in group 2.
      Postoperatively, there was no mortality or major morbidity. Two patients in group
      1 experienced temporary anal incontinence (A3 and B1 stages). There were no
      reported adverse effects on sexual life, but significant clinical improvement was
      observed in both groups after surgery. Manometrically, there was a significant
      improvement in MARP, FLAC, RS, UTDV and MTV in both groups (significantly better
      in the early postoperative period in the stapled group). Also, follow-up
      defaecographic findings showed a significant decrease in the rectocele size in
      all the patients. CONCLUSION: Transanal repair of rectocele is a safe and
      effective technique in improving symptomatic rectocele. Stapled repair offers the
      advantage of short operative time, no comorbidity, and shorter hospital stay.

PMID- 21070567
TI  - Comment on 'Colorectal foreign bodies: a systematic review'.

PMID- 21070568
TI  - The majority of colorectal resections require an open approach, even in units
      with a special interest in laparoscopic surgery.
AB  - AIM: Proponents suggest that laparoscopic colorectal resection might be
      achievable in up to 90% of cases, while keeping conversion rates below 10%. This
      unselected prospective case series reports on the proportion of patients having a
      completed laparoscopic colorectal resection in two units where laparoscopic
      colorectal practice is well established and readily available. METHOD: All
      patients undergoing elective and emergency colorectal resection during a 6-month
      period were identified. The underlying pathology and the surgical approach
      (laparoscopic or open) were recorded. The contraindications to laparoscopic
      resection were also documented. The need and rationale for conversion to an open
      approach were recorded. RESULTS: In total, 205 consecutive patients (160 elective
      and 45 emergency procedures) underwent colorectal resection for malignancy [117
      (57%) patients] and benign pathology [88 (43%) patients]. Laparoscopic resection
      was attempted in 127/205 (62%) patients and 31/127 (24%) of these were converted
      to open surgery. The main reasons for not attempting laparoscopic resection were
      locally advanced disease and emergency surgery. The commonest reasons for
      conversion were advanced disease and to allow completion of rectal dissection
      and/or cross-stapling of the rectum. CONCLUSION: Despite a special interest in
      laparoscopic colorectal surgery of the two colorectal units who provided the data
      for this study, fewer than half (96/205; 47%) of the patients in this consecutive
      unselected series who were undergoing major colorectal resection had the
      procedure completed laparoscopically.

PMID- 21070570
TI  - Comparison of hilar clamping and non-hilar clamping partial nephrectomy for
      tumours involving a solitary kidney.
AB  - OBJECTIVE: * To compare outcomes of hilar clamping and non-hilar clamping partial
      nephrectomy for tumours involving a solitary functional kidney. PATIENTS AND
      METHODS: * Between 1990 and 2009, 104 partial nephrectomies, excluding bench and
      autotransplant procedures, were performed on solitary functional kidneys. * An
      institutional review board-approved retrospective review was performed analyzing
      patient demographics, operative data, complications, oncological outcomes and
      estimated glomerular filtration rate (GFR). * GFR was calculated using the
      abbreviated Modification of Diet in Renal Disease equation. * Preoperative GFR
      was compared to Early GFR (lowest measured GFR 7-100 days postoperatively) and to
      Late GFR (GFR 101-365 days postoperatively). * Multiple linear regression
      analysis was performed to assess covariates affecting Late GFR. * Kaplan-Meier
      estimator was utilized to compare renal cell carcinoma (RCC) specific survival
      and non-RCC-related survival. RESULTS: * In total, 29 partial nephrectomies with
      hilar clamping and 75 partial nephrectomies without hilar clamping were performed
      in solitary kidneys. Median follow-up was 57 months. * There was no difference in
      tumour size, location and the number of tumours resected between the two groups.
      Mean ischaemia time for the clamping group was 25 min. * Some 97% of the clamping
      procedures were performed with cold ischaemia. * There was no difference in intra
      operative estimated blood loss, transfusion requirement or length of hospital
      stay. * The complication rate and spectrum of complications were similar between
      the two groups. * The two groups had similar preoperative GFR and Early GFR. The
      non-clamping group had a significantly smaller percent decrease in Late GFR
      (11.8% vs 27.7%, P= 0.01) than the clamping group. * The non-clamping group was
      significantly more likely to have a less than 10% decrease in Late GFR compared
      to the clamping group (60.9% vs 17.7%, P= 0.002). * On multivariate analysis,
      only hilar clamping was significantly associated with decreased Late GFR
      (estimate 15.0, P= 0.02). * Surgical margin positivity rate was higher in the
      clamping group (21% vs 4%, P= 0.01); however, the local recurrence rate between
      the two groups was similar. * The clamping and non-clamping groups had similar 5
      year RCC-specific survival and 5-year non-RCC-related survival. CONCLUSIONS: *
      Partial nephrectomy without hilar clamping in solitary kidneys provides similar
      cancer control compared to partial nephrectomy with hilar clamping. * Partial
      nephrectomy without clamping was associated with superior preservation of Late
      GFR. * No difference was detected in GFR early after surgery, possibly indicating
      that there may be ongoing renal loss after hilar clamping.

PMID- 21070569
TI  - Validity and reliability of the patient's perception of intensity of urgency
      scale in overactive bladder.
AB  - OBJECTIVE: * To assess the measurement characteristics of the Patient Perception
      of Intensity of Urgency Scale (PPIUS) in patients with overactive bladder (OAB).
      PATIENTS AND METHODS: * Adult women with at least a 3-month history of OAB. The
      design was a 4-week, double-blind, randomized, placebo-controlled trial of
      transdermal oxybutynin, with a 2-week placebo run-in and 8-week, open-label
      extension. * Symptom improvement was assessed using 3-day bladder diaries
      incorporating the PPIUS, and disease-specific health-related quality of life was
      assessed using the King's Health Questionnaire (KHQ). Convergent validity was
      shown by correlation with the KHQ, and other bladder diary variables. Known
      groups validity was assessed by comparison of baseline mean urge ratings, and
      urgency episode frequency for continent and incontinent patients, and by
      comparison with the same measures from a historical control group of 40
      asymptomatic female volunteers. * Between- and within-groups responsiveness was
      assessed using standardized effect sizes (Cohen's d and effect size r).
      Reliability was assessed for the two arms of the trial at different time points
      and intervals, using intraclass correlation (ICC) and a t-test for the difference
      between mean scores. RESULTS: * In total, 96 women were randomized. Urgency
      episode frequency showed moderate correlation with total KHQ score (r = 0.500, P
      < 0.001) and with daytime and night-time voiding frequency. * There were
      significant differences in continent and incontinent subgroups for mean urge
      ratings (difference in means, -0.61/void, P < 0.001), and urgency episodes
      (difference in means, -2.67 episodes/day, P < 0.001), as well as between OAB
      patients and normal controls (mean urge rating: difference in means 1.22 per
      void, P < 0.001; urgency episodes: difference in means 2.93 episodes/day, P <
      0.001). * Between-groups analysis of effect size found that urgency episode
      frequency (d = 0.679, r = 0.321) was more responsive than mean urge rating (d =
      0.480, r = 0.233). In both subgroups, urgency episode frequency (d = 0.421-0.454,
      r = 0.206-0.222) had better within-groups responsiveness than mean urge rating. *
      Urgency episodes (ICC, 0.65-0.81) were measured more reliably than urgency
      urinary incontinence episodes (ICC, 0.50-0.65). CONCLUSIONS: * Assessment of
      urgency episodes using the PPIUS shows good reliability, excellent known groups
      validity, high responsiveness and convergence with subjective measures of
      severity. * PPIUS is freely available, and should be useful in both clinical
      practice and research studies when assessing women with urgency, with or without
      urgency urinary incontinence.

PMID- 21070571
TI  - Robotic extended pelvic lymphadenectomy for bladder cancer with increased nodal
      yield.
AB  - STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the
      subject? and What does the study add? The standard of care for invasive bladder
      cancer is open radical cystectomy with the extent of pelvic lymph node dissection
      impacting oncological outcomes. Scepticism remains regarding whether an adequate
      node dissection can be performed in minimally-invasive fashion as previously
      reported nodal yields of laparoscopic or robotic lymphadenectomy are well below
      those reported with open surgery. This study demonstrates that extended pelvic
      lymphadenectomy can be performed robotically with equivalent nodal yields to open
      series from centres of excellence. OBJECTIVE: To report our initial experience
      with robot-assisted extended pelvic lymph node dissection (ePLND) using a
      standardized open template. PATIENTS AND METHODS: In total, 15 consecutive
      patients underwent robotic radical cystectomy at a single center by a single
      surgeon using a standard dissection template. Operating time, time to perform
      ePLND, pathological stage, estimated blood loss, length of hospital stay, number
      of nodes obtained and nodal positivity were assessed. Postoperative complications
      and re-admissions were reviewed. RESULTS: The mean (range) age and body mass
      index was 66 (46-87) years and 29 (22-43) kg/m2, respectively. The mean (range)
      operating time and ePLND time was 423 (300-506) min and 107 (66-160) min. Mean
      (range) estimated blood loss was 160 (50-500) mL. The mean (range) and median
      length of hospital stay were 3.4 (3-7) days and 3 days, respectively. The mean
      (range) nodal yield was 41.8 (18-67) nodes, with greater than 25 nodes in 13
      patients. Three patients were found to have nodal positivity. Of the fifteen
      patients, four received neoadjuvant chemotherapy. Two patients were re-admitted
      for postoperative complications within 30 days. There were no complications
      directly resulting from the ePLND. CONCLUSIONS: Robot-assisted ePLND at the time
      of cystectomy can be safely and effectively performed on the robotic platform
      with comparable nodal yields to open series at centers of excellence for
      cystectomy. Nodal yields are likely to comprise a factor related to the effort of
      the surgeon, and not the method by which the lymphadenectomy is performed.

PMID- 21070572
TI  - C-reactive protein is a strong predictor for anaemia in renal cell carcinoma:
      role of IL-6 in overall survival.
AB  - OBJECTIVE: * To elucidate the association of progression of advanced renal cell
      carcinoma with anaemia and investigate factors influencing tumor-associated
      anaemia. PATIENTS AND METHODS: * We analyzed different clinical variables to
      study associations with anaemia in 86 metastatic renal cell carcinoma patients. *
      45 (52%) of patients had already developed anaemia prior to therapy. RESULTS: *
      Anaemic patients had an increase in the serum markers C-reactive protein (CRP),
      IL-6 and erythropoietin (EPO). In addition we observed substantial correlation
      between IL-6 and CRP serum levels (R = 0.639, P < 0.0001). * Univariate logistic
      regression analysis revealed that patients with IL-6 >10 pg/mL had a considerable
      increase in risk for anaemia (odds ratio 3.86, P= 0.003). * In addition, patients
      with CRP >0.7 mg/dL had a very strong increase in risk for anaemia (OR = 14.08, P
      < 0.0001). * Stepwise multivariate logistic regression analysis confirmed CRP
      >0.7 mg/mL as the only independent predictor for anaemia. Cox-regression modeling
      selected serum IL-6 as the strongest independent prognostic indicator (hazard
      ratio 3.58, P < 0.0001). CONCLUSION: * Anaemia depends on serum IL-6, which is a
      strong inductor of CRP and regulator of the iron-transport. Serum IL-6 may be
      considered as a target to treat cancer-related anaemia.

PMID- 21070573
TI  - Altered transcription factor E3 expression in unclassified adult renal cell
      carcinoma indicates adverse pathological features and poor outcome.
AB  - OBJECTIVES: To evaluate the clinical and pathologic features and the prognostic
      relevance of unclassified RCC with -TFE3 over-expression in our adult series.
      Recent studies suggest that renal cell carcinomas (RCCs) associated with the
      newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene
      fusions) can be found among adults with RCC showing a very aggressive disease
      course. MATERIAL AND METHODS: We evaluated tumour specimens from 25 patients with
      unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary
      academic centre. Immunohistochemistry was performed using monoclonal antibody for
      TFE3 C-terminal section, taking nuclear label into consideration. RT-PCR
      technique was performed for ASPL-TFE3 gene fusion on two tumours with available
      frozen tissue. RESULTS: Of the 25 cases analyzed, 8 (32%) showed positivity for
      TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL-TFE3 gene
      fusion also showed TFE3 over-expression. Fifty percent of the positive patients
      had lymph node metastatic disease, whereas only one TFE3-negative patient (5.8%)
      showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3
      positive patients, three had a vena cava thrombus (37.5%). Seven of the eight
      positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In
      comparison, five of 17 (29.4%) TFE3-negative patients had a high Fuhrman grade.
      Five of eight TFE3-positive patients relapsed rapidly at 3 month follow-up;
      conversely none of the negative cases relapsed. At 36-month mean follow-up, 5
      year cancer-specific survival was 15.6% for TFE3-positive patients and 87.5% for
      TFE3-negative patients (P < 0.001). CONCLUSION: Patients with unclassified RCC
      and TFE3 positivity have a grim prognosis due to their advanced stage at
      presentation and aggressive biologic features compared with the TFE3-negative
      unclassified RCC cases.

PMID- 21070575
TI  - Prostate cancer immunology - an update for Urologists.
AB  - A better understanding of the immune processes in the pathogenesis and
      progression of prostate cancer (CaP) may point the way towards improved treatment
      modalities. The challenge is to amplify immune responses to combat tumour escape
      mechanisms. Infection and inflammation may have a role in prostate
      carcinogenesis, including the newly discovered xenotropic murine leukaemia virus
      (XMRV). These inflammatory states damage defence mechanisms and induce a high
      proliferative state favouring further mutation and impaired immune surveillance.
      With this knowledge we are able to explore the use of immunotherapy to rejuvenate
      the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic
      agent for metastatic androgen independent CaP, has resulted in improved survival
      and might be the first immunotherapeutic agent to obtain approval for CaP
      treatment. This short review will focus on the growing body of evidence
      suggesting an immunity-based link between CaP and inflammation and infection.

PMID- 21070574
TI  - Modulation of smooth muscle tonus in the lower urinary tract: interplay of myosin
      light-chain kinase (MLCK) and MLC phosphatase (MLCP).
AB  - OBJECTIVE: To assess and compare the expression and activity of myosin light
      chain kinase (MLCK) and MLC phosphatase (MLCP) in rat bladder and urethra.
      MATERIALS AND METHODS: Bladder and urethral smooth muscles were obtained from 2
      month-old female Sprague-Dawley rats. They were analysed by real-time polymerase
      chain reaction for the mRNA expression of MLCK and myosin phosphatase-targeting
      subunit of protein phosphatase type 1 (MYPT1, a subunit of MLCP). Levels of MLCK
      and MYPT1 mRNA expression were determined as a ratio to the expression of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The tissues were also analysed
      by Western blotting for MLCK and MYPT1 protein expression as a ratio to the
      expression of beta-actin. A two-step enzymatic activity assay using
      phosphorylated and dephosphorylated smooth muscle myosin was used to assess MLCK
      and MLCP activity. RESULTS: MLCK mRNA expression was higher in the bladder than
      in the urethra [mean (sd) ratio to GAPDH: 0.26 (0.17) vs 0.14 (0.12); P = 0.09].
      MYPT1 mRNA expression was significantly higher in the bladder than in the urethra
      [mean (sd) ratio to GAPDH: 2.31 (1.04) vs 0.56 (0.36); P = 0.001]. Expression of
      both MLCK and MYPT1 protein was significantly higher in the bladder compared with
      the urethra [mean (sd) ratio to beta-actin: 1.63 (0.25) vs 0.91 (0.29) and 0.97
      (0.10) vs 0.37 (0.29), respectively; both P < 0.001]. Enzymatic assay identified
      significantly greater MLCK activity in the bladder than in the urethra. While,
      MLCP activity was lower in the bladder than in the urethra. CONCLUSION: In
      healthy young female rats, MLCK activity is higher and MLCP activity is lower in
      the bladder relative to the urethra. These differences probably play a role in
      modulating the functional differences between bladder and urethral smooth muscle
      tone.

PMID- 21070576
TI  - Extranodal extension in node-positive bladder cancer: the continuing controversy.
AB  - OBJECTIVE: * To examine whether extranodal extension (ENE) has an impact on the
      outcome of node-positive patients who underwent radical cystectomy for bladder
      cancer. PATIENTS AND METHODS: * Of 543 consecutive patients who underwent radical
      cystectomy for urothelial carcinoma of the bladder between 1990 and 2007, 112
      patients with lymph node metastasis detected on histological examination were
      evaluated with regard to recurrence-free survival (RFS) and disease-specific
      survival (DSS) based on ENE status. RESULTS: * The overall 5-year RFS and DSS
      rates were 22.3% and 33.8%, respectively. ENE was observed in 41 (36.6%) of the
      112 patients. * The presence of ENE was associated with advanced pathological
      nodal status (P= 0.004), more positive lymph nodes (P= 0.006), and higher lymph
      node density (P < 0.001). * The incidence of positive ENE increased with large
      positive lymph node diameter (P < 0.001). * Multivariate analysis showed that
      lymph node density (hazard ratio (HR) = 2.39, 95% CI 1.09-5.24, P= 0.029; and HR
      = 3.13, 1.43-6.84, P= 0.004) and use of adjuvant chemotherapy (HR = 1.80, 1.02
      3.20, P= 0.041; and HR = 2.07, 1.13-3.79, P= 0.018) were significant predictors
      of RFS and DSS, respectively. * After adjustment for other prognostic factors,
      ENE was not significantly related to RFS (P= 0.825) and DSS (P= 0.961) by
      multivariate analysis. CONCLUSIONS: * The presence of ENE was not an independent
      prognostic factor in node-positive patients after radical cystectomy for bladder
      cancer. * Additional prospective studies are needed to determine the independent
      prognostic role of ENE.

PMID- 21070577
TI  - Endoscopic management of vesicoureteral reflux in adult women.
AB  - OBJECTIVE: * To describe our endoscopic management of adult women with
      vesicoureteral reflux (VUR) and associated outcomes. PATIENTS AND METHODS: * We
      retrospectively identified 19 adult women who presented for the endoscopic
      treatment of VUR from November 2001 to January 2008. * Each patient was diagnosed
      with VUR by voiding cystourethrogram or nuclear cystourethrogram after an episode
      of pyelonephritis or recurrent urinary tract infections with renal scarring on
      ultrasound. * A dimercaptosuccinic acid renal scan was performed prior to
      treatment. All patients underwent endoscopic treatment with
      dextranomer/hyaluronic acid copolymer (Deflux). Patients with bilateral VUR
      received bilateral injections during the same procedure. * Follow-up imaging was
      obtained and success was strictly defined as no degree of VUR. Patients with
      residual VUR received repeat endoscopic treatment. RESULTS: * Nineteen patients
      with a mean age of 22 years old (range 18-33 years old) underwent endoscopic
      treatment for VUR. A total of 79% (15/19) had pre-existing risk factors for VUR,
      including prior open anti-reflux surgery (26%), family history of VUR (26%) and
      childhood diagnosis of VUR (26%). * Imaging revealed that 47% (9/19) had renal
      scarring and 26% (5/19) had bilateral VUR. The success rate was 79% (19/24) after
      one treatment, 92% (22/24) after 5 patients received a second treatment, and 96%
      (23/24) after 2 patients received a third treatment. There were no perioperative
      complications. CONCLUSION: * Endoscopic management of VUR is both safe and
      effective in adult women.

PMID- 21070578
TI  - Radical cystectomy for BCG failure: has the timing improved in recent years?
AB  - OBJECTIVE: * To analyse if there is a trend in recent years towards performing
      radical cystectomy (RC) before muscle invasion or extravesical spread after
      failure of bacille Calmette-Guerin (BCG) for high grade Ta/T1 bladder cancer.
      Although BCG is indicated for prophylaxis after endoscopic tumour resection there
      is still a risk of progression. PATIENTS AND METHODS: * A retrospective analysis
      of our RC database (1992-2008) was performed to identify patients who underwent
      RC after receiving BCG. * Relevant clinical and pathological data for the
      patients with clinical stage Ta, T1 and/or Tis at initial transurethral resection
      of bladder tumour were analysed. * Pathological stage and survival for patients
      undergoing RC from 2003 to 2007 (group 2) were compared with those for patients
      operated between 1992 and 2002 (group 1). RESULTS: * A total of 152 patients were
      included (75 in group 2 and 77 in group 1). Both groups were similar in T-stage
      before BCG initiation, number of BCG cycles received and time interval to RC. *
      There was no change in the proportion of patients undergoing RC with >= pT2
      bladder cancer in recent years (P= 0.5). * Fifty-two percent of group 2 and 43%
      of group 1 had >= pT2 BC. The 5-year survival was similar. CONCLUSIONS: * Despite
      concerns about delay in performing RC for patients failing one or more courses of
      BCG we have not observed a trend towards a lower pathological stage for patients
      undergoing RC after BCG. * A high proportion of patients have muscle-invasive
      bladder cancer; more than 10% have lymph node metastasis.

PMID- 21070579
TI  - Loss of androgen receptor expression is not associated with pathological stage,
      grade, gender or outcome in bladder cancer: a large multi-institutional study.
AB  - OBJECTIVE: * To investigate androgen receptor (AR) expression in a large series
      of patients with bladder cancer (BC) because data on a limited number of patients
      showed that loss of AR expression was associated with invasive BC. PATIENTS AND
      METHODS: * A total of 472 patients with urothelial bladder carcinoma (UBC) from
      two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays
      comprising both non-muscle-invasive UBC (n= 167) and muscle-invasive UBC (n= 305)
      were accrued and immunohistochemical staining for AR was performed. * We used
      bright-field microscopy imaging coupled with advanced colour detection software
      to detect, classify and count stained cellular objects and manual scoring. *
      Results obtained in Dallas were blindly reviewed and validated in Toronto and
      samples randomly chosen were further analysed in Rochester, NY, USA. RESULTS: *
      The AR were positively expressed in 61/472 (12.9%) bladder tumours. No
      statistically significant difference in AR expression between men and women was
      observed. * Only 9.0% of non-muscle-invasive BC expressed the AR compared with
      15.1% of muscle-invasive tumours (P= 0.059). The highest percentage of AR
      positivity (28.9% of cases) was found in T2 tumours. * There was no statistically
      significant difference in death from BC, time to death, or time to recurrence
      between AR-positive and AR-negative cases. CONCLUSION: * In contrast to previous
      reports, based on our large BC series, we did not observe a decrease in AR
      protein expression in bladder tumours with increased pathological stage. Our data
      do not suggest that loss of AR expression is gender-related nor is it associated
      with invasive BC.

PMID- 21070580
TI  - Does the surgical technique for management of the distal ureter influence the
      outcome after nephroureterectomy?
AB  - Study Type - Therapy (case series) Level of Evidence 4 What's known on the
      subject? and What does the study add? The resection of the distal ureter and its
      orifice is an oncological principle during radical nephroureterectomy which is
      based on the fact that it represents a part of the urinary tract exposed to a
      considerable risk of recurrence. After removal of the proximal part it is hardly
      possible to image or approach it by endoscopy during follow-up. Recent
      publications on survival after nephroureterectomy do not allow the conclusion
      that removal of distal ureter and bladder cuff are useless. Several techniques of
      distal ureter removal have been described but they are not equivalent in term of
      oncological safety. * The standard treatment of upper urinary tract urothelial
      carcinomas (UUT-UCs) must obey oncological principles, which consist of a
      complete en bloc resection of the kidney and the ureter, as well as excision of a
      bladder cuff to avoid tumour seeding. * The open technique is the 'gold standard'
      of treatment to which all other techniques developed are necessarily compared,
      and various surgical procedures have been described. * The laparoscopic stapling
      technique maintains a closed system but risks leaving behind the ureteric and
      bladder cuff segments. * Transvesical laparoscopic detachment and ligation is a
      valid approach from an oncological stance but is technically difficult. The major
      inconvenience of the transurethral resection of the ureteric orifice and
      intussusception techniques is the potential for tumour seeding. * Management of
      the distal ureter via the robot-assisted laparoscopic method is technically
      feasible, but outcomes from these procedures are still preliminary. * Therefore,
      prospective comparative studies with more thorough explorations of these
      techniques are needed to solve the dilemma of the management of the distal ureter
      during nephroureterectomy. However, bladder cuff excision should remain the
      standard of care irrespective of the stage of the disease.

PMID- 21070581
TI  - Influence of age and bladder dysfunction on the contractile properties of
      isolated human detrusor smooth muscle.
AB  - OBJECTIVE: To test the hypothesis that the in vitro contractile properties of
      human detrusor smooth muscle are dependent on the age, gender and lower urinary
      tract pathology of the patient. MATERIALS AND METHODS: Contractions were elicited
      in isolated human detrusor smooth muscle preparations by nerve-mediated
      electrical field stimulation, agonist application (carbachol, alpha,beta
      methylene ATP and high-K solutions) or direct muscle electrical stimulation.
      Biopsies (n = 227) were obtained from four groups of patients with: stable
      bladders (control), bladder outlet obstruction (BOO), idiopathic (IDO), or
      neurogenic (NDO) detrusor overactivity. RESULTS: The magnitude of nerve-mediated
      contractions declined as a function of patients' age in each of the BOO, IDO and
      NDO groups but not in the control group. Contractions elicited by direct muscle
      activation (10 uM carbachol or electrical stimulation with 20 ms pulses in the
      presence of 1 uM tetrodotoxin) did not vary with patient age. Carbachol
      contractions were significantly smaller in samples from NDO bladders. Atropine
      resistance was more prevalent in the pathology groups compared with the control
      group and was greatest in the IDO group. There was no influence of age in the
      prevalence or magnitude of atropine-resistant contractions in any group. Muscle
      excitability to direct electrical stimulation was similar in all groups.
      CONCLUSIONS: In the human bladder there is no evidence for a decline of detrusor
      smooth muscle contractility or excitability as a function of age, nor any gender
      difference or presence of pathology. In the pathology groups there was evidence
      for a decline of functional innervation with age.

PMID- 21070582
TI  - De novo renal cell carcinoma of native and graft kidneys in renal transplant
      recipients.
AB  - OBJECTIVE: * To access the epidemiological, clinical and survival features of
      renal transplant patients with de novo renal cell carcinoma of native and graft
      kidneys. PATIENTS AND METHODS: * We performed a retrospective examination of the
      data of 2001 consecutive renal transplant recipients at our centre between
      November 1979 and January 2010. RESULTS: * In the patient cohort examined, 30
      renal cell carcinomas were observed in 26 individuals (incidence 1.5%) with 25
      tumours in the native and five in allograft kidneys. Mean tumour size in surgical
      specimens was 44 +/- 36 mm. The rate of papillary cancer was 37.5%. * After a
      mean follow-up of 58.6 +/- 62.3 months, 15.4% of the patients died from cancer
      and 57.7% were in complete remission. * Overall and tumour-specific survival
      rates at 1, 5 and 10 years were 86.1%, 75.1% and 43.8%, and 90.4%, 83.5% and
      66.8%, respectively. CONCLUSIONS: * Due to increasingly improved survival after
      renal transplantation, de novo malignancies might soon become the main cause of
      intermediate- or long-term mortality. * Current data support an increased risk of
      renal cell carcinoma in renal transplant recipients in a particularly aggressive
      way, but low tendency for metachronous contralateral evolution. * With continuous
      radiological follow-ups, acceptable oncological outcome can be achieved. Graft
      tumours may have a favourable prognosis.

PMID- 21070583
TI  - Diabetes mellitus and health-related quality of life in prostate cancer: 5-year
      results from the Prostate Cancer Outcomes Study.
AB  - Study Type--Therapy (outcomes research) Level of Evidence 2b. What's known on the
      subject? and What does the study add? Comorbid diabetes can affect prostate
      cancer treatment decision-making and outcomes. Few longitudinal studies have
      investigated the effect of comorbid diabetes on general and cancer-specific
      health-related quality of life (HRQL) in prostate cancer. Our study found that
      men with prevalent diabetes (pre-prostate cancer diagnosis) generally had the
      poorest general HRQL, urinary control and sexual function scores over time,
      independent of treatment. Non-diabetic men had the best scores and men with
      incident diabetes (post-prostate cancer diagnosis) reported intermediate scores.
      OBJECTIVE * To investigate the association between prostate cancer, diabetes, and
      long-term general and cancer-specific health-related quality of life (HRQL) in a
      cohort of men with non-metastatic prostate cancer. PATIENTS AND METHODS * We used
      data from self-administered surveys to assess the HRQL of men with localized or
      locally advanced disease at 6 (baseline), 12, 24, and 60 months after initial
      diagnosis. * We examined changes in general and cancer-specific HRQL with
      repeated measures analyses using a mixed-model approach. RESULTS * In total, we
      evaluated 1811 men, including 13% with prevalent (pre-prostate cancer diagnosis)
      diabetes, 12% with incident (post-prostate cancer diagnosis) diabetes, and 75%
      who never reported being diagnosed with diabetes. * Generally, men with prevalent
      diabetes had the poorest scores on general HRQL and non-diabetic men the best
      scores, independent of treatment. * Similarly, men with prevalent diabetes had
      the lowest urinary control and sexual function scores over time, while men
      without diabetes had the highest scores. Men with incident diabetes reported
      intermediate scores. CONCLUSION * Prostate cancer survivors with comorbid
      diabetes have poorer general and cancer-specific HRQL than those without
      diabetes.

PMID- 21070584
TI  - Complications after bladder augmentation or substitution in children: a
      prospective study of 86 patients.
AB  - OBJECTIVE: * To evaluate complications after urinary bladder augmentation or
      substitution in a prospective study in children. PATIENTS AND METHODS: * Data of
      86 patients who underwent urinary bladder augmentation (80 patients) or
      substitution (6 patients) between 1988 and 2008 at the authors' institute were
      analysed. * Ileocystoplasty occurred in 32, colocystoplasty in 30 and
      gastrocystoplasty in 18. Urinary bladder substitution using the large bowel was
      performed in six patients. * All patients empty their bladder by intermittent
      clean catheterization (ICC), 30 patients via their native urethra and 56 patients
      through continent abdominal stoma. Mean follow-up was 8.6 years. * Rate of
      complications and frequency of surgical interventions were statistically analysed
      (two samples t-test for proportions) according to the type of gastrointestinal
      part used. RESULTS: * In all, 30 patients had no complications. In 56 patients,
      there were a total of 105 complications (39 bladder stones, 16 stoma
      complications, 11 bowel obstructions, 5 reservoir perforations, 7 VUR
      recurrences, 1 ureteral obstruction, 4 vesico-urethral fistulae, 4 orchido
      epididymitis, 4 haematuria-dysuria syndrome, 3 decreased bladder
      capacity/compliance, 3 pre-malignant histological changes, 1 small bowel
      bacterial overgrowth and 7 miscellaneous). * In 25 patients, more than one
      complication occurred and required 91 subsequent surgical interventions. Patients
      with colocystoplasty had significantly more complications (P < 0.05), especially
      more stone formation rate (P < 0.001) and required more post- operative
      interventions (P < 0.05) than patients with gastrocystoplasty and
      ileocystoplasty. CONCLUSIONS: * Urinary bladder augmentation or substitution is
      associated with a large number of complications, particularly after
      colocystoplasty. * Careful patient selection, adequate preoperative information
      and life-long follow-up are essential for reduction, early detection and
      management of surgical and metabolic complications in patients with bladder
      augmentation or substitution.

PMID- 21070586
TI  - Egg size and offspring quality: a meta-analysis in birds.
AB  - Parents affect offspring fitness by propagule size and quality, selection of
      oviposition site, quality of incubation, feeding of dependent young, and their
      defence against predators and parasites. Despite many case studies on each of
      these topics, this knowledge has not been rigorously integrated into individual
      parental care traits for any taxon. Consequently, we lack a comprehensive,
      quantitative assessment of how parental care modifies offspring phenotypes. This
      meta-analysis of 283 studies with 1805 correlations between egg size and
      offspring quality in birds is intended to fill this gap. The large sample size
      enabled testing of how the magnitude of the relationship between egg size and
      offspring quality depends on a number of variables. Egg size was positively
      related to nearly all studied offspring traits across all stages of the offspring
      life cycle. Not surprisingly, the relationship was strongest at hatching but
      persisted until the post-fledging stage. Morphological traits were the most
      closely related to egg size but significant relationships were also found with
      hatching success, chick survival, and growth rate. Non-significant effect sizes
      were found for egg fertility, chick immunity, behaviour, and life-history or
      sexual traits. Effect size did not depend on whether chicks were raised by their
      natural parents or were cross-fostered to other territories. Effect size did not
      depend on species-specific traits such as developmental mode, clutch size, and
      relative size of the egg, but was larger if tested in captive compared to wild
      populations and between rather than within broods. In sum, published studies
      support the view that egg size affects juvenile survival. There are very few
      studies that tested the relationship between egg size and the fecundity component
      of offspring fitness, and no studies on offspring survival as adults or on global
      fitness. More data are also needed for the relationships between egg size and
      offspring behavioural and physiological traits. It remains to be established
      whether the relationship between egg size and offspring performance depends on
      the quality of the offspring environment. Positive effect sizes found in this
      study are likely to be driven by a causal effect of egg size on offspring
      quality. However, more studies that control for potential confounding effects of
      parental post-hatching care, genes, and egg composition are needed to establish
      firmly this causal link.

PMID- 21070587
TI  - Recent spatial and temporal changes in body size of terrestrial vertebrates:
      probable causes and pitfalls.
AB  - Geographical and temporal variations in body size are common phenomena among
      organisms and may evolve within a few years. We argue that body size acts much
      like a barometer, fluctuating in parallel with changes in the relevant key
      predictor(s), and that geographical and temporal changes in body size are
      actually manifestations of the same drivers. Frequently, the principal predictors
      of body size are food availability during the period of growth and ambient
      temperature, which often affects food availability. Food availability depends on
      net primary productivity that, in turn, is determined by climate and weather
      (mainly temperature and precipitation), and these depend mainly on solar
      radiation and other solar activities. When the above predictors are related to
      latitude the changes have often been interpreted as conforming to Bergmann's
      rule, but in many cases such interpretations should be viewed with caution due to
      the interrelationships among various environmental predictors. Recent temporal
      changes in body size have often been related to global warming. However, in many
      cases the above key predictors are not related to either latitude and/or year,
      and it is the task of the researcher to determine which particular environmental
      predictor is the one that determines food availability and, in turn, body size.
      The chance of discerning a significant change in body size depends to a large
      extent on sample size (specimens/year). The most recent changes in body size are
      probably phenotypic, but there are some cases in which they are partly genetic.

PMID- 21070588
TI  - Fluid-deposited graphite and its geobiological implications in early Archean
      gneiss from Akilia, Greenland.
AB  - Graphite, interpreted as altered bioorganic matter in an early Archean, ca. 3.83
      Ga-old quartz-amphibole-pyroxene gneiss on Akilia Island, Greenland, has
      previously been claimed to be the earliest trace of life on Earth. Our
      petrographic and Raman spectroscopy data from this gneiss reveal the occurrence
      of graphitic material with the structure of nano-crystalline to crystalline
      graphite in trails and clusters of CO2, CH4 and H2O bearing fluid inclusions.
      Irregular particles of graphitic material without a fluid phase, representing
      decrepitated fluid inclusions are common in such trails too, but occur also as
      dispersed individual or clustered particles. The occurrence of graphitic material
      associated with carbonic fluid inclusions is consistent with an abiologic, fluid
      deposited origin during a poly-metamorphic history. The evidence for fluid
      deposited graphitic material greatly complicates any claim about remnants of
      early life in the Akilia rock.

PMID- 21070589
TI  - Social context, stress, and plasticity of aging.
AB  - Positive social contact is an important factor in healthy aging, but our
      understanding of how social interactions influence senescence is incomplete. As
      life expectancy continues to increase because of reduced death rates among
      elderly, the beneficial role of social relationships is emerging as a cross
      cutting theme in research on aging and healthspan. There is a need to improve
      knowledge on how behavior shapes, and is shaped by, the social environment, as
      well as needs to identify and study biological mechanisms that can translate
      differences in the social aspects of behavioral efforts, relationships, and
      stress reactivity (the general physiological and behavioral response-pattern to
      harmful, dangerous or unpleasant situations) into variation in aging. Honey bees
      (Apis mellifera) provide a genetic model in sociobiology, behavioral
      neuroscience, and gerontology that is uniquely sensitive to social exchange.
      Different behavioral contact between these social insects can shorten or extend
      lifespan more than 10-fold, and some aspects of their senescence are reversed by
      social cues that trigger aged individuals to express youthful repertoires of
      behavior. Here, I summarize how variation in social interactions contributes to
      this plasticity of aging and explain how beneficial and detrimental roles of
      social relationships can be traced from environmental and biological effects on
      honey bee physiology and behavior, to the expression of recovery-related
      plasticity, stress reactivity, and survival during old age. This system provides
      intriguing opportunities for research on aging.

PMID- 21070591
TI  - Familial longevity is marked by enhanced insulin sensitivity.
AB  - Insulin resistance is a risk factor for various age-related diseases. In the
      Leiden Longevity study, we recruited long-lived siblings and their offspring.
      Previously, we showed that, compared to controls, the offspring of long-lived
      siblings had a better glucose tolerance. Here, we compared groups of offspring
      from long-lived siblings and controls for the relation between insulin and
      glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin
      action using a two-step hyperinsulinemic-euglycemic clamp (n = 24 subjects).
      Groups of offspring and controls were similar with regard to sex distribution,
      age, and body mass index. We observed a positive bi-phasic linear relationship
      between ln (insulin) levels and nonfasted glucose with a steeper slope from
      10.7mU L(-1) insulin onwards in controls compared to offspring (P = 0.02). During
      the clamp study, higher glucose infusion rate was required to maintain euglycemia
      during high-dose insulin infusion (P = 0.036) in offspring, reflecting higher
      whole-body insulin sensitivity. After adjustment for sex, age, and fat mass, the
      insulin-mediated glucose disposal rate (GDR) was higher in offspring than
      controls (42.5 +/- 2.7 vs. 33.2 +/- 2.7 micromol kg(-1) min(-1) , mean +/- SE, P
      = 0.025). The insulin-mediated suppression of endogenous glucose production and
      lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was
      significantly correlated with the mean age of death of the parents. In
      conclusion, offspring from long-lived siblings are marked by enhanced peripheral
      glucose disposal. Future research will focus on identifying the underlying
      biomolecular mechanisms, with the aim to promote health in old age.

PMID- 21070592
TI  - Health care provider perceptions of pain treatment in Hispanic patients.
AB  - Despite increasing numbers of Hispanic patients in the United States, this group
      continues to face disparities in access and quality of pain treatment. Although
      previous surveys have examined treatment disparities experienced by minority
      patients, none have provided a provider-centric perspective on issues and
      concerns surrounding pain relief among pain patients of Hispanic/Latino origin.
      The goal of this study was to assess the relationship between provider
      characteristics (ie, Spanish fluency, Hispanic caseload size, and experience with
      Hispanic pain patients) and their perceptions of pain treatment in these
      patients. One hundred eighty-seven health professionals completed an online
      survey. The major findings indicated that: (1) less than 20% of health
      professionals treating Hispanic pain patients reported Spanish proficiency at an
      advanced level; (2) surveyed health professionals were involved treating a
      significant proportion of Hispanic patients in their caseloads, but reported a
      lack of cultural competence training; (3) Spanish fluency and experience with
      Hispanic pain patients exerts a strong effect on the use of established pain
      treatment practices; (4) providers with greater Spanish fluency report a
      significantly greater effect of patients' cultural beliefs and attitudes on
      treatment; and (5) providers did not regard cultural or language barriers as
      significantly impacting opioid prescribing or patient compliance.

PMID- 21070590
TI  - Dietary effects on body composition, glucose metabolism, and longevity are
      modulated by skeletal muscle mitochondrial uncoupling in mice.
AB  - Little is known about how diet and energy metabolism interact in determination of
      lifespan under ad libitum feeding. From 12 weeks of age until death, male and
      female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle
      mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different
      semisynthetic diets differing in macronutrient ratio: control (high
      carbohydrate/low-fat-HCLF) and two high-fat diets: high-carbohydrate/high-fat
      (HCHF), and low-carbohydrate/high-fat (LCHF). Compared to control and LCHF, HCHF
      feeding rapidly and significantly increased body fat content in WT. Median
      lifespan of WT was decreased by 33% (HCHF) and 7% (LCHF) compared to HCLF. HCHF
      significantly increased insulin resistance (HOMA) of WT from 24 weeks on compared
      to control. TG mice had lower lean body mass and increased energy expenditure,
      insulin sensitivity, and maximum lifespan (+10%) compared to WT. They showed a
      delayed development of obesity on HCHF but reached similar maximum adiposity as
      WT. TG median lifespan was only slightly reduced by HCHF (-7%) and unaffected by
      LCHF compared to control. Correlation analyses showed that decreased longevity
      was more strongly linked to a high rate of fat gain than to adiposity itself.
      Furthermore, insulin resistance was negatively and weight-specific energy
      expenditure was positively correlated with longevity. We conclude that (i)
      dietary macronutrient ratios strongly affected obesity development, glucose
      homeostasis, and longevity, (ii) that skeletal muscle mitochondrial uncoupling
      alleviated the detrimental effects of high-fat diets, and (iii) that early
      imbalances in energy homeostasis leading to increased insulin resistance are
      predictive for a decreased lifespan.

PMID- 21070593
TI  - Role of tissue factor in feto-maternal development: a xiphos.
AB  - In this review, the dual role of tissue factor (TF) in pregnancy is described. On
      the one hand, TF is required for embryonic and placental development in a
      successful pregnancy, and on the other hand, pathologic expression of TF can lead
      to serious pregnancy complications in humans and mice. Human studies show
      increased TF levels in plasma, amniotic fluid and and/or placentas of abnormal
      pregnancies affected by miscarriages, preterm birth, or pre-eclampsia.
      Interestingly, using two mouse models, we found that blood-borne TF plays a
      crucial role in the pathogenesis of pregnancy complications. TF on neutrophils
      and monocytes is a critical mediator in trophoblast injury and embryo damage in
      pregnancy loss induced by antiphospholipid antibodies and in the antibody
      independent CBA/J * DBA/2 model of miscarriages. Blockade of TF or genetic
      diminution prevented pregnancy complications, suggesting that TF may be a good
      target for therapy in patients with recurrent miscarriages, pregnancy loss, and
      pre-eclampsia. In addition, statins, which downregulate TF, may constitute a good
      therapeutic option for women with pregnancy complications. Clinical trials should
      be conducted to confirm these observations in women.

PMID- 21070594
TI  - High percentage of non-diagnostic compression ultrasonography results and the
      diagnosis of ipsilateral recurrent proximal deep vein thrombosis: a rebuttal.

PMID- 21070585
TI  - Hippocampal memory consolidation during sleep: a comparison of mammals and birds.
AB  - The transition from wakefulness to sleep is marked by pronounced changes in brain
      activity. The brain rhythms that characterize the two main types of mammalian
      sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to
      be involved in the functions of sleep. In particular, recent theories suggest
      that the synchronous slow-oscillation of neocortical neuronal membrane
      potentials, the defining feature of SWS, is involved in processing information
      acquired during wakefulness. According to the Standard Model of memory
      consolidation, during wakefulness the hippocampus receives input from neocortical
      regions involved in the initial encoding of an experience and binds this
      information into a coherent memory trace that is then transferred to the
      neocortex during SWS where it is stored and integrated within preexisting memory
      traces. Evidence suggests that this process selectively involves direct
      connections from the hippocampus to the prefrontal cortex (PFC), a multimodal,
      high-order association region implicated in coordinating the storage and recall
      of remote memories in the neocortex. The slow-oscillation is thought to
      orchestrate the transfer of information from the hippocampus by temporally
      coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs
      are synchronous bursts of hippocampal activity, during which waking neuronal
      firing patterns are reactivated in the hippocampus and neocortex in a coordinated
      manner. Thalamocortical spindles are brief 7-14 Hz oscillations that may
      facilitate the encoding of information reactivated during SWRs. By temporally
      coupling the readout of information from the hippocampus with conditions
      conducive to encoding in the neocortex, the slow-oscillation is thought to
      mediate the transfer of information from the hippocampus to the neocortex.
      Although several lines of evidence are consistent with this function for
      mammalian SWS, it is unclear whether SWS serves a similar function in birds, the
      only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on
      our review of research on avian sleep, neuroanatomy, and memory, although
      involved in some forms of memory consolidation, avian sleep does not appear to be
      involved in transferring hippocampal memories to other brain regions. Despite
      exhibiting the slow-oscillation, SWRs and spindles have not been found in birds.
      Moreover, although birds independently evolved a brain region--the caudolateral
      nidopallium (NCL)--involved in performing high-order cognitive functions similar
      to those performed by the PFC, direct connections between the NCL and hippocampus
      have not been found in birds, and evidence for the transfer of information from
      the hippocampus to the NCL or other extra-hippocampal regions is lacking.
      Although based on the absence of evidence for various traits, collectively, these
      findings suggest that unlike mammalian SWS, avian SWS may not be involved in
      transferring memories from the hippocampus. Furthermore, it suggests that the
      slow-oscillation, the defining feature of mammalian and avian SWS, may serve a
      more general function independent of that related to coordinating the transfer of
      information from the hippocampus to the PFC in mammals. Given that SWS is
      homeostatically regulated (a process intimately related to the slow-oscillation)
      in mammals and birds, functional hypotheses linked to this process may apply to
      both taxonomic groups.

PMID- 21070595
TI  - A role for Rab10 in von Willebrand factor release discovered by an AP-1
      interactor screen in C. elegans.
AB  - BACKGROUND: Endothelial von Willebrand factor (VWF) mediates platelet adhesion
      and acts as a protective chaperone to clotting factor VIII. Rapid release of
      highly multimerized VWF is particularly effective in promoting hemostasis. To
      produce this protein, an elaborate biogenesis is required, culminating at the
      trans-Golgi network (TGN) in storage within secretory granules called Weibel
      Palade bodies (WPB). Failure to correctly form these organelles can lead to
      uncontrolled secretion of low-molecular-weight multimers of VWF. The TGN
      associated adaptor AP-1 and its interactors clathrin, aftiphilin and gamma
      synergin are essential to initial WPB formation at the Golgi apparatus, and thus
      to VWF storage and secretion. OBJECTIVES: To identify new proteins implicated in
      VWF storage and/or secretion. METHODS: A genomewide RNA interference (RNAi)
      screen was performed in the Nematode C. elegans to identify new AP-1 genetic
      interactors. RESULTS: The small GTPase Rab10 was found to genetically interact
      with a partial loss of function of AP-1 in C. elegans. We investigated Rab10 in
      human primary umbilical vein endothelial cells (HUVECs). We report that Rab10 is
      enriched at the Golgi apparatus, where WPB are formed, and that in cells where
      Rab10 expression has been suppressed by siRNA, VWF secretion is altered: the
      amount of rapidly released VWF was significantly reduced. We also found that
      Rab8A has a similar function. CONCLUSION: Rab10 and Rab8A are new cytoplasmic
      factors implicated in WPB biogenesis that play a role in generating granules that
      can rapidly respond to secretagogue.

PMID- 21070596
TI  - Mature endothelium and neurons are simultaneously derived from embryonic stem
      cells by 2D in vitro culture system.
AB  - The connections existing between vessels and nerves go beyond the structural
      architecture of vascular and nervous systems to comprise cell fate determination.
      The analysis of functional/molecular links that interconnect endothelial and
      neural commitments requires a model in which the two differentiation programs
      take place at the same time in an artificial controllable environment. To this
      regard, this work presents an in vitro model to differentiate embryonic stem (ES)
      cells simultaneously into mature neurons and endothelial cells. Murine ES cells
      are differentiated within an artificial environment composed of PA6 stromal cells
      and a serum-free medium. Upon these basal culture conditions ES cells
      preferentially differentiate into neurons. The addition of basic fibroblast
      growth factor (FGF2) to the medium allows the simultaneous maturation of neurons
      and endothelial cells, whereas bone morphogenetic protein (BMP)4 drives
      endothelial differentiation to the disadvantage of neural commitment. The
      responsiveness of the system to exogenous cytokines was confirmed by genes
      expression analysis that revealed a significant up-regulation of endothelial
      genes in presence of FGF2 and a massive down-regulation of the neural markers in
      response to BMP4. Furthermore, the role played by single genes in determining
      endothelial and neural fate can be easily explored by knocking down the
      expression of the target gene with lentiviruses carrying the corresponding shRNA
      sequence. The possibility to address the neural and the endothelial fate
      separately or simultaneously by exogenous stimuli combined with an efficient gene
      silencing strategy make this model an optimal tool to identify environmental
      signals and genes pathways involved in both endothelial and neural specification.

PMID- 21070597
TI  - AMD3100 is a potent antagonist at CXCR4(R334X) , a hyperfunctional mutant
      chemokine receptor and cause of WHIM syndrome.
AB  - WHIM is an acronym for a rare immunodeficiency syndrome (OMIM #193670) caused by
      autosomal dominant mutations truncating the C-terminus of the chemokine receptor
      CXC chemokine receptor 4 (CXCR4). WHIM mutations may potentiate CXCR4 signalling,
      suggesting that the United States Food and Drug Administration (FDA)-approved
      CXCR4 antagonist AnorMED3100 (AMD3100) (also known as Plerixafor) may be
      beneficial in WHIM syndrome. We have tested this at the preclinical level by
      comparing Chinese hamster ovary (CHO) and K562 cell lines matched for expression
      of recombinant wild-type CXCR4 (CXCR4(WT)) and the most common WHIM variant of
      CXCR4 (CXCR4(R334X)), as well as leucocytes from a WHIM patient with the
      CXCR4(R334X) mutation versus healthy controls. We found that CXCR4(R334X)
      mediated modestly increased signalling (~2-fold) in all functional assays tested,
      but strongly resisted ligand-dependent down-regulation. AMD3100 was equipotent
      and equieffective as an antagonist at CXCR4(R334X) and CXCR4(WT) . Together, our
      data provide further evidence that CXCR4(R334X) is a gain-of-function mutation,
      and support clinical evaluation of AMD3100 as mechanism-based treatment in
      patients with WHIM syndrome.

PMID- 21070598
TI  - Targeting AML through DR4 with a novel variant of rhTRAIL.
AB  - Despite progress in the treatment of acute myelogenous leukaemia (AML) the
      outcome often remains poor. Tumour necrosis factor related apoptosis-inducing
      ligand (TRAIL) is a promising therapeutic agent in many different types of
      tumours, but AML cells are relatively insensitive to TRAIL-induced apoptosis.
      Here we show that TRAIL-induced apoptosis in AML cells is predominantly mediated
      by death receptor 4 (DR4) and not DR5. Therefore, we constructed a variant of
      TRAIL (rhTRAIL-C3) that is a strong inducer of DR4-mediated apoptosis. TRAIL-C3
      demonstrated much stronger pro-apoptotic activity than wild-type (WT) TRAIL in a
      panel of AML cell lines as well as in primary AML blasts. The higher pro
      apoptotic potential was further enhanced when the TRAIL mutant was used in
      combination with BMS-345541, a selective inhibitor of inhibitor-kappaB kinases.
      It illustrates that combination of this TRAIL variant with chemotherapeutics or
      other targeted agents can kill AML with high efficacy. This may represent a major
      advantage over the currently used therapies that have serious toxic side effects.
      The high efficacy of rhTRAIL-C3 containing therapies may enable the use of lower
      drug doses to reduce the toxic side effects and improve patient outcome. Our
      findings suggest that the rational design of TRAIL variants that target DR4
      potentiate the death-inducing activity of TRAIL and offer a novel therapeutic
      strategy for the treatment of AML.

PMID- 21070599
TI  - Mesothelial cell differentiation into osteoblast- and adipocyte-like cells.
AB  - Serosal pathologies including malignant mesothelioma (MM) can show features of
      osseous and/or cartilaginous differentiation although the mechanism for its
      formation is unknown. Mesothelial cells have the capacity to differentiate into
      cells with myofibroblast, smooth muscle and endothelial cell characteristics.
      Whether they can differentiate into other cell types is unclear. This study tests
      the hypothesis that mesothelial cells can differentiate into cell lineages of the
      embryonic mesoderm including osteoblasts and adipocytes. To examine this, a
      functional assay of bone formation and an adipogenic assay were performed in
      vitro with primary rat and human mesothelial cells maintained in osteogenic or
      adipogenic medium (AM) for 0-26 days. Mesothelial cells expressed increasing
      levels of alkaline phosphatase, an early marker of the osteoblast phenotype, and
      formed mineralized bone-like nodules. Mesothelial cells also accumulated lipid
      indicative of a mature adipocyte phenotype when cultured in AM. All cells
      expressed several key osteoblast and adipocyte markers, including osteoblast
      specific runt-related transcription factor 2, and demonstrated changes in mRNA
      expression consistent with epithelial-to-mesenchymal transition. In conclusion,
      these studies confirm that mesothelial cells have the capacity to differentiate
      into osteoblast- and adipocyte-like cells, providing definitive evidence of their
      multipotential nature. These data strongly support mesothelial cell
      differentiation as the potential source of different tissue types in MM tumours
      and other serosal pathologies, and add support for the use of mesothelial cells
      in regenerative therapies.

PMID- 21070600
TI  - Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance
      and relapse in leukaemia.
AB  - Multidrug resistance (MDR) and disease relapse are challenging clinical problems
      in the treatment of leukaemia. Relapsed disease is frequently refractory to
      chemotherapy and exhibits multiple drug resistance. Therefore, it is important to
      identify the mechanism by which cancer cells develop resistance. In this study,
      we used microRNA (miRNA) microarray and qRT-PCR approaches to investigate the
      expression of miRNAs in three leukaemia cell lines with different degrees of
      resistance to doxorubicin (DOX) compared with their parent cell line, K562. The
      expression of miR-331-5p and miR-27a was inversely correlated with the expression
      of a drug-resistant factor, P-glycoprotein (P-gp), in leukaemia cell lines with
      gradually increasing resistance. The development of drug resistance is regulated
      by the expression of the P-gp. Transfection of the K562 and, a human
      promyelocytic cell line (HL) HL60 DOX-resistant cells with miR-331-5p and miR
      27a, separately or in combination, resulted in the increased sensitivity of cells
      to DOX, suggesting that correction of altered expression of miRNAs may be used
      for therapeutic strategies to overcome leukaemia cell resistance. Importantly,
      miR-331-5p and miR-27a were also expressed at lower levels in a panel of relapse
      patients compared with primary patients at diagnosis, further illustrating that
      leukaemia relapse might be a consequence of deregulation of miR-331-5p and miR
      27a.

PMID- 21070601
TI  - Virtual crossmatch approach to maximize matching in paired kidney donation.
AB  - We developed and tested a new computer program to match maximal sets of
      incompatible live donor/recipient pairs from a national paired kidney donation
      (PKD) registry. Data of 32 incompatible pairs included ABO and 4 digit-high
      resolution donor and recipient HLA antigens and recipient's HLA antibodies. Three
      test runs were compared, in which donors were excluded from matching to
      recipients with either donor-specific antibodies (DSA) >8000MFI (mean fluorescent
      intensity) at low-resolution (Run 1) or >8000MFI at high-resolution (Run 2) or
      >2000MFI and high-resolution (Run 3). Run 1 identified 22 703 possible
      combinations, with 20 pairs in the top ranked, Run 2 identified 24 113
      combinations, with 19 pairs in the top ranked and Run 3 identified 8843
      combinations, with 17 pairs in the top ranked. Review of DSA in Run 1 revealed
      that six recipients had DSA 2000-8000MFI causing a possible positive crossmatch
      resulting in breakdown of two 3-way and three 2-way chains. In Run 2, four
      recipients had DSA 2000-8000MFI, also potentially causing breakdown of three 2
      way chains. The more prudent approach of excluding from matching recipients with
      DSA with >2000MFI reduces the probability of matched pairs having a positive
      crossmatch without significantly decreasing the number of possible transplants.

PMID- 21070602
TI  - Young transplant surgeons and NIH funding.
AB  - Transplant surgeons have historically been instrumental in advancing the science
      of transplantation. However, research in the current environment inevitably
      requires external funding, and the classic career development pathway for a
      junior investigator is the NIH K award. We matched transplant surgeons who
      completed fellowships between 1998 and 2004 with the NIH funding database, and
      also queried them regarding research effort and attitudes. Of 373 surgeons who
      completed a fellowship, only 6 (1.8%) received a K award; of these, 3
      subsequently obtained R-level funding. An additional 5 individuals received an R
      level grant within their first 5 years as faculty without a K award, 3 of whom
      had received a prior ASTS-sponsored award. Survey respondents reported extensive
      research experience during their training (78.8% spent median 24 months), a high
      proportion of graduate research degrees (36%), and a strong desire for more
      research time (78%). However, they reported clinical burdens and lack of
      mentorship as their primary perceived barriers to successful research careers.
      The very low rate of NIH funding for young transplant surgeons, combined with
      survey results that indicate their desire to participate in research, suggest
      institutional barriers to access that may warrant attention by the ASTS and the
      transplant surgery community.

PMID- 21070603
TI  - Impact of MELD on waitlist outcome of retransplant candidates.
AB  - Under the current allocation system for liver transplantation (LTx), primary and
      retransplantation (ReTx) are treated identically. The aims of this study were (1)
      to compare the risk of death between ReTx and primary LTx candidates at a given
      MELD score and (2) to gauge the impact of the MELD-based allocation system on the
      waitlist outcome of ReTx candidates. Based on data of all waitlist registrants in
      the United States between 2000 and 2006, unique adult patients with chronic liver
      disease were identified and followed forward to determine mortality within six
      months of registration. There were a total of 45,943 patients waitlisted for
      primary LTx and 2081 registered for ReTx. In the MELD era (n = 30,175), MELD was
      significantly higher among ReTx candidates than primary LTx candidates (median,
      21 vs. 15). Within a range of MELD scores where most transplantation took place,
      mortality was comparable between ReTx and primary candidates after adjusting for
      MELD. The probability for LTx increased significantly following implementation of
      the MELD-based allocation in both types of candidates. We conclude that by and
      large, primary and ReTx candidates fare equitably under the current MELD-based
      allocation system, which has contributed to a significant increase in the
      probability of LTx.

PMID- 21070605
TI  - Association of marital status with access to renal transplantation.
AB  - In this report we evaluated the association of marital status with access to
      renal transplantation. We analyzed data from the USRDS. In patients with ESRD
      aged >= 27 (mean age of first marriage in the US), we analyzed the association of
      marital status with two outcomes: (1) likelihood of being placed on the waiting
      list for renal transplantation or first transplant, (2) likelihood of receiving
      kidney transplant in patients already listed. We analyzed marital status as a
      categorical variable: (1) not married (including never been married and widowed);
      (2) divorced or separated; and (3) currently married. Subgroups based on age,
      race, sex, donor type and diabetic status were also analyzed. After adjustments
      for the included independent variables and compared to individuals never married
      or widowed, those who were divorced/separated (HR 1.55, p < 0.001) and currently
      married (HR 1.54, p < 0.001) had a higher likelihood of being placed on the
      transplant waiting list. Once listed, married individuals had higher chances of
      getting transplanted as well (HR 1.28, p = 0.033). This trend was consistent in
      most of the subgroups studied. We demonstrated that being married is associated
      with better access to renal transplantation compared to those who were never
      married/widowed.

PMID- 21070604
TI  - Selective targeting of human alloresponsive CD8+ effector memory T cells based on
      CD2 expression.
AB  - Costimulation blockade (CoB), specifically CD28/B7 inhibition with belatacept, is
      an emerging clinical replacement for calcineurin inhibitor-based
      immunosuppression in allotransplantation. However, there is accumulating evidence
      that belatacept incompletely controls alloreactive T cells that lose CD28
      expression during terminal differentiation. We have recently shown that the CD2
      specific fusion protein alefacept controls costimulation blockade-resistant
      allograft rejection in nonhuman primates. Here, we have investigated the
      relationship between human alloreactive T cells, costimulation blockade
      sensitivity and CD2 expression to determine whether these findings warrant
      potential clinical translation. Using polychromatic flow cytometry, we found that
      CD8(+) effector memory T cells are distinctly high CD2 and low CD28 expressors.
      Alloresponsive CD8(+) CD2(hi) CD28(-) T cells contained the highest proportion of
      cells with polyfunctional cytokine (IFNgamma, TNF and IL-2) and cytotoxic
      effector molecule (CD107a and granzyme B) expression capability. Treatment with
      belatacept in vitro incompletely attenuated allospecific proliferation, but
      alefacept inhibited belatacept-resistant proliferation. These results suggest
      that highly alloreactive effector T cells exert their late stage functions
      without reliance on ongoing CD28/B7 costimulation. Their high CD2 expression
      increases their susceptibility to alefacept. These studies combined with in vivo
      nonhuman primate data provide a rationale for translation of an immunosuppression
      regimen pairing alefacept and belatacept to human renal transplantation.

PMID- 21070606
TI  - L-selectin is dispensable for T regulatory cell function postallogeneic bone
      marrow transplantation.
AB  - In murine models, the adoptive transfer of CD4(+) /CD25(+) regulatory T cells
      (T(regs) ) inhibited graft-versus-host disease (GvHD). Previous work has
      indicated a critical role for the adhesion molecule L-selectin (CD62L) in the
      function of T(regs) in preventing GvHD. Here we examined the capacity of naive
      wild-type (WT), CD62L(-/-) and ex vivo expanded CD62L(Lo) T(regs) to inhibit
      acute GvHD. Surprisingly, we found that CD62L(-/-) T(regs) were potent
      suppressors of GvHD, whereas CD62L(Lo) T(regs) were unable to inhibit disease
      despite being functionally competent to suppress allo T cell responses in vitro.
      Concomitant with improved outcomes, WT and CD62L(-/-) T(regs) significantly
      reduced liver pathology and systemic pro-inflammatory cytokine production,
      although CD62L(-/-) T(regs) were less effective in reducing lung pathology. While
      accumulation of CD62L(-/-) T(regs) in GvHD target organs was equivalent to WT
      T(regs) , CD62L(-/-) T(regs) did not migrate as well as WT T(regs) to peripheral
      lymph nodes (PLNs) over the first 2 weeks posttransplantation. This work
      demonstrated that CD62L was dispensable for T(reg) -mediated protection from
      GvHD.

PMID- 21070607
TI  - Enhancing the expanded criteria donor policy as an intervention to improve kidney
      allocation: is it actually a 'net-zero' model?
AB  - In the United States, relatively little progress has been made in recent years to
      improve the efficiency and effectiveness of deceased donor kidney allocation.
      Despite enactment of the Expanded Criteria Donor (ECD) Policy in 2002, known
      inequities and suboptimal utility of donated kidneys persist. In contrast with
      dialysis patients with shorter predicted life expectancies, those with longer
      predicted lifetimes can often improve their survival by waiting longer for a
      Standard Criteria Donor (SCD) kidney. Yet, a substantial fraction of these
      candidates accept ECD kidneys, often poorly HLA matched. Meanwhile, waitlist
      mortality continues to rise, particularly among older transplant candidates.
      Despite required consent processes for candidates to list for ECD kidneys,
      centers appear to interpret and implement ECD policy differently-some list
      candidates selectively while others list nearly their entire candidate pool. To
      ensure more efficient and effective implementation of ECD policy across centers,
      we advocate for (1) more oversight and guidance in directing patients to the ECD
      list who stand to benefit the most from receipt of an ECD kidney; and (2)
      enhanced transparency of center-level ECD consent and listing practices. More
      uniform implementation of ECD policy could improve efficiency and effectiveness
      of deceased donor kidney allocation without deleteriously impacting equity.

PMID- 21070608
TI  - Red plaques and difficult-to-treat asthma.

PMID- 21070609
TI  - Conservation of the egg envelope digestion mechanism of hatching enzyme in
      euteleostean fishes.
AB  - We purified two hatching enzymes, namely high choriolytic enzyme (HCE; EC
      3.4.24.67) and low choriolytic enzyme (LCE; EC 3.4.24.66), from the hatching
      liquid of Fundulus heteroclitus, which were named Fundulus HCE (FHCE) and
      Fundulus LCE (FLCE). FHCE swelled the inner layer of egg envelope, and FLCE
      completely digested the FHCE-swollen envelope. In addition, we cloned three
      Fundulus cDNAs orthologous to cDNAs for the medaka precursors of egg envelope
      subunit proteins (i.e. choriogenins H, H minor and L) from the female liver.
      Cleavage sites of FHCE and FLCE on egg envelope subunit proteins were determined
      by comparing the N-terminal amino acid sequences of digests with the sequences
      deduced from the cDNAs for egg envelope subunit proteins. FHCE and FLCE cleaved
      different sites of the subunit proteins. FHCE efficiently cleaved the Pro-X-Y
      repeat regions into tripeptides to dodecapeptides to swell the envelope, whereas
      FLCE cleaved the inside of the zona pellucida domain, the core structure of egg
      envelope subunit protein, to completely digest the FHCE-swollen envelope. A
      comparison showed that the positions of hatching enzyme cleavage sites on egg
      envelope subunit proteins were strictly conserved between Fundulus and medaka.
      Finally, we extended such a comparison to three other euteleosts (i.e. three
      spined stickleback, spotted halibut and rainbow trout) and found that the egg
      envelope digestion mechanism was well conserved among them. During evolution, the
      egg envelope digestion by HCE and LCE orthologs was established in the lineage of
      euteleosts, and the mechanism is suggested to be conserved.

PMID- 21070611
TI  - Heptanol triggers cardioprotection via mitochondrial mechanisms and mitochondrial
      potassium channel opening in rat hearts.
AB  - AIM: To investigate mechanisms behind heptanol (Hp)-induced infarct size
      reduction and in particular if protection by pre-treatment with Hp is triggered
      through mitochondrial mechanisms. METHODS: Langendorff perfused rat hearts,
      isolated mitochondria and isolated myocytes were used. Infarct size,
      mitochondrial respiration, time to mitochondrial permeability transition pore
      (MPTP) opening and AKT and glycogen synthase kinase 3 beta (GSK-3beta)
      phosphorylation were examined. RESULTS: Pre-treatment with Hp reduced infarct
      size from 29.7 +/- 3.4% to 12.6 +/- 2.1%. Mitochondrial potassium channel
      blockers 5-hydroxy decanoic acid (5HD) blocking mitoK(ATP) and paxilline (PAX)
      blocking mitoK(Ca) abolished cardioprotective effect of Hp (Hp + 5HD 36.7 +/-
      2.9% and Hp + PAX 40.2 +/- 2.8%). Hp significantly reduced respiratory control
      ratio in both subsarcolemmal and interfibrillar mitochondria in a dose-dependent
      manner (0.5-5.0 mm). The ADP oxygen ratio was also significantly reduced by Hp (2
      mm). Laser scanning confocal microscopy of tetramethylrhodamine-loaded isolated
      rat myocytes using line scan mode showed that Hp increased time to MPTP opening.
      Western blot analysis showed that pre-treatment with Hp increased phosphorylation
      of AKT and GSK-3beta before ischaemia and after 30 min of global ischaemia.
      CONCLUSION: Pre-treatment with Hp protects the heart against ischaemia
      reperfusion injury. This protection is most likely mediated via mitochondrial
      mechanisms which initiate a signalling cascade that converges on inhibition of
      opening of MPTP.

PMID- 21070612
TI  - The cell biology of human hair follicle pigmentation.
AB  - Although we have made significant progress in understanding the regulation of the
      UVR-exposed epidermal-melanin unit, we know relatively little about how human
      hair follicle pigmentation is regulated. Progress has been hampered by gaps in
      our knowledge of the hair growth cycle's controls, to which hair pigmentation
      appears tightly coupled. However, pigment cell researchers may have overly
      focused on the follicular melanocytes of the nocturnal and UVR-shy mouse as a
      proxy for human epidermal melanocytes. Here, I emphasize the epidermis-follicular
      melanocyte pluralism of human skin, as research models for vitiligo, alopecia
      areata and melanoma, personal care/cosmetics innovation. Further motivation could
      be in finding answers to why hair follicle and epidermal pigmentary units remain
      broadly distinct? Why melanomas tend to originate from epidermal rather than
      follicular melanocytes? Why multiple follicular melanocyte sub-populations exist?
      Why follicular melanocytes are more sensitive to aging influences? In this
      perspective, I attempt to raise the status of the human hair follicle melanocyte
      and highlight some species-specific issues involved which the general reader of
      the pigmentation literature (with its substantial mouse-based data) may not fully
      appreciate.

PMID- 21070610
TI  - Structural determinants of PERK inhibitor potency and selectivity.
AB  - The unfolded protein response (UPR) is a coordinated program that promotes cell
      survival under conditions of endoplasmic reticulum stress and is required in
      tumor progression as well. To date, no specific small molecule inhibitor
      targeting this pathway has been identified. Pancreatic endoplasmic reticulum
      kinase (PERK), one of the UPR transducers, is an eIF2alpha kinase. Compromising
      PERK function inhibits tumor growth in mice, suggesting that PERK may be a cancer
      drug target, but identifying a specific inhibitor of any kinase is challenging.
      The goal of this study was to identify some pair-wise receptor-ligand atomic
      contacts that confer selective PERK inhibition. Compounds selectively inhibiting
      PERK-mediated phosphorylation in vitro were identified using an initial virtual
      library screen, followed by structure-activity hypothesis testing. The most
      potent PERK selective inhibitors utilize three specific kinase active site
      contacts that, when absent from chemically similar compounds, abrogates the
      inhibition: (i) a strong van der Waals contact with PERK residue Met7, (ii)
      interactions with the N-terminal portion of the activation loop, and (iii) groups
      providing electrostatic complementarity to Asp144. Interestingly, the activation
      loop contact is required for PERK selectivity to emerge. Understanding these
      structure-activity relationships may accelerate rational PERK inhibitor design.

PMID- 21070613
TI  - Stress-sensing toll-like receptor as a driver of angiogenesis.

PMID- 21070614
TI  - Evaluation of phacoemulsification-induced oxidative stress and damage of cultured
      human corneal endothelial cells in different solutions using redox fluorometry
      microscopy.
AB  - PURPOSE: To describe the basic concept of redox fluorometry microscopy and
      investigate its efficacy in evaluating the state of cultured human corneal
      endothelial cells in different solutions when ultrasonic energy was applied in
      vitro. METHODS: Human corneal endothelial cells from human donor tissue not
      suitable for transplantation were cultured. A phacoemulsification probe with a 30
      degrees  round, 1.1-mm TurboSonics((r)) ABSTM Tip (Alcon, Fort Worth, Texas) was
      introduced into culture dishes filled with balanced salt solution (BSS) and BSS
      plus (Alcon, Fort Worth, Texas). Cellular autofluorescence images were obtained
      using a Zeiss inverted microscope. The redox fluorometric ratio, which can be
      related to cellular metabolism, mitochondrial distribution patterns, which can
      shift in reaction to environmental changes, and cell size were analysed with a
      software program. RESULTS: Human corneal endothelial cells exposed to increasing
      phacoemulsification times and ultrasonic energy displayed dose-dependent
      decreases in redox ratios. At a lower ultrasonic power and time, BSS plus showed
      significantly less change in redox ratio than BSS and control (p < 0.05, Mann
      Whitney test). As ultrasonic power and time increased, BSS plus had no more
      significance. CONCLUSION: Redox fluorometry, with further technological
      improvement, might be an interesting and potentially useful tool for evaluation
      of phacoemulsification-induced corneal endothelial damage and screening of
      protective agents in vitro.

PMID- 21070615
TI  - Acupuncture for treating dry eye: a randomized placebo-controlled trial.
AB  - PURPOSE: To evaluate the efficacy and safety of acupuncture for ocular symptoms,
      tear film stability and tear secretion in dry eye patients. METHODS: This is a
      randomized, patient-assessor blinded, sham acupuncture controlled trial. Forty
      two participants with defined moderate to severe dry eye underwent acupuncture
      treatment three times a week for 3 weeks. Seventeen standard points (GV23;
      bilateral BL2, GB14, TE23, Ex1, ST1 and GB20; and unilateral SP3, LU9, LU10 and
      HT8 on the left for men and right for women) with 'de qi' manipulation for the
      verum acupuncture group and seventeen sham points of shallow penetration without
      other manipulation for the sham group were applied during the acupuncture
      treatment. Differences were measured using the ocular surface disease index
      (OSDI), the visual analogue scale (VAS) of ocular discomfort, the tear film break
      up time (BUT) and the Schimer I test with anaesthesia. In addition, adverse
      events were recorded. RESULTS: There were no statistically significant
      differences between results on the OSDI, VAS, BUT or Schimer I tests from
      baseline between the verum and sham acupuncture groups. However, results from the
      within-group analysis showed that the OSDI and VAS in both groups and the BUT in
      the verum acupuncture group were significantly improved after 3 weeks of
      treatment. No adverse events were reported during this trial. CONCLUSION: Both
      types of acupuncture improved signs and symptoms in dry-eye patients after a 4
      week treatment. However, verum acupuncture did not result in better outcomes than
      sham acupuncture.

PMID- 21070616
TI  - Biomarkers in atrial fibrillation, ventricular arrhythmias, and sudden cardiac
      death.
AB  - Cardiac arrhythmias including atrial fibrillation, ventricular tachycardia, and
      ventricular fibrillation are important causes of cardiovascular morbidity and
      mortality. Although they usually occur in the setting of structural heart
      disease, these arrhythmias can be the primary manifestation of subclinical
      cardiovascular disease and have deleterious consequences including stroke, heart
      failure, and death. Investigational efforts have focused on developing risk
      stratification algorithms and diagnostic methods to identify patients who are
      most likely to sustain cardiac arrhythmias and benefit from early pharmacologic
      and interventional therapies. This review highlights important clinical and
      translational studies that identify potential biological markers to predict the
      onset of cardiac arrhythmias and their complications. Particular focus is placed
      on mechanisms involving the neurohormonal system, inflammation, the renin
      angiotensin-aldosterone system, and metabolic pathways.

PMID- 21070617
TI  - Thrombolytics and myocardial infarction.
AB  - Coronary artery disease is the single leading cause of death in the United
      States. Occlusion of the coronary artery was identified to be the cause of
      myocardial infarction almost a century ago. Following a series of investigations,
      streptokinase was discovered and demonstrated to be beneficial for the treatment
      of patients with acute myocardial infarction in terms of reducing short- and long
      term mortality. Newer agents including tissue plasminogen activators such as
      alteplase, reteplase, tenecteplase were developed subsequently. In the present
      era, thrombolytic therapy and primary percutaneous coronary intervention has
      revolutionized the way patients with acute myocardial infarction are managed
      resulting in significant reduction in cardiovascular death. This article provides
      an overview of the various thrombolytic agents utilized in the management of
      patients with acute myocardial infarction.

PMID- 21070618
TI  - Nociceptin/orphanin phenylalanine glutamine (FQ) receptor and cardiovascular
      disease.
AB  - Nociceptin/Orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ receptor.
      N/OFQ acts directly on blood vessels to elicit vasodilation. This review will
      describe the peripheral cardiovascular effects of N/OFQ observed in studies
      conducted in vitro and in vivo, along with those designed to characterize
      systemic cardiovascular effects resulting from direct injection into brain
      tissue. Emphasis is placed on the cerebrovascular action of N/OFQ and its
      function considered in the setting of central nervous system (CNS) pathology.
      Although N/OFQ is unlikely to cross the blood-brain barrier because of its size,
      use of N/OFQ antagonists to alleviate the potentially deleterious action of
      centrally released N/OFQ may be of therapeutic importance in treatment of
      cerebral ischemia of diverse origin, such as stroke and traumatic brain injury.
      Targeting N/OFQ may also be of therapeutic importance in alleviating the
      hyperemia and pain associated with joint inflammation.

PMID- 21070620
TI  - Are substitution rates and RNA editing correlated?
AB  - BACKGROUND: RNA editing is a post-transcriptional process that, in seed plants,
      involves a cytosine to uracil change in messenger RNA, causing the translated
      protein to differ from that predicted by the DNA sequence. RNA editing occurs
      extensively in plant mitochondria, but large differences in editing frequencies
      are found in some groups. The underlying processes responsible for the
      distribution of edited sites are largely unknown, but gene function, substitution
      rate, and gene conversion have been proposed to influence editing frequencies.
      RESULTS: We studied five mitochondrial genes in the monocot order Alismatales,
      all showing marked differences in editing frequencies among taxa. A general
      tendency to lose edited sites was observed in all taxa, but this tendency was
      particularly strong in two clades, with most of the edited sites lost in parallel
      in two different areas of the phylogeny. This pattern is observed in at least
      four of the five genes analyzed. Except in the groups that show an unusually low
      editing frequency, the rate of C-to-T changes in edited sites was not
      significantly higher that in non-edited 3rd codon positions. This may indicate
      that selection is not actively removing edited sites in nine of the 12 families
      of the core Alismatales. In all genes but ccmB, a significant correlation was
      found between frequency of change in edited sites and synonymous substitution
      rate. In general, taxa with higher substitution rates tend to have fewer edited
      sites, as indicated by the phylogenetically independent correlation analyses. The
      elimination of edited sites in groups that lack or have reduced levels of editing
      could be a result of gene conversion involving a cDNA copy (retroprocessing). If
      so, this phenomenon could be relatively common in the Alismatales, and may have
      affected some groups recurrently. Indirect evidence of retroprocessing without a
      necessary correlation with substitution rate was found mostly in families
      Alismataceae and Hydrocharitaceae (e.g., groups that suffered a rapid elimination
      of all their edited sites, without a change in substitution rate). CONCLUSIONS:
      The effects of substitution rate, selection, and/or gene conversion on the
      dynamics of edited sites in plant mitochondria remain poorly understood. Although
      we found an inverse correlation between substitution rate and editing frequency,
      this correlation is partially obscured by gene retroprocessing in lineages that
      have lost most of their edited sites. The presence of processed paralogs in plant
      mitochondria deserves further study, since most evidence of their occurrence is
      circumstantial.

PMID- 21070621
TI  - The cost-effectiveness of the RSI QuickScan intervention programme for computer
      workers: Results of an economic evaluation alongside a randomised controlled
      trial.
AB  - BACKGROUND: The costs of arm, shoulder and neck symptoms are high. In order to
      decrease these costs employers implement interventions aimed at reducing these
      symptoms. One frequently used intervention is the RSI QuickScan intervention
      programme. It establishes a risk profile of the target population and
      subsequently advises interventions following a decision tree based on that risk
      profile. The purpose of this study was to perform an economic evaluation, from
      both the societal and companies' perspective, of the RSI QuickScan intervention
      programme for computer workers. In this study, effectiveness was defined at three
      levels: exposure to risk factors, prevalence of arm, shoulder and neck symptoms,
      and days of sick leave. METHODS: The economic evaluation was conducted alongside
      a randomised controlled trial (RCT). Participating computer workers from 7
      companies (N = 638) were assigned to either the intervention group (N = 320) or
      the usual care group (N = 318) by means of cluster randomisation (N = 50). The
      intervention consisted of a tailor-made programme, based on a previously
      established risk profile. At baseline, 6 and 12 month follow-up, the participants
      completed the RSI QuickScan questionnaire. Analyses to estimate the effect of the
      intervention were done according to the intention-to-treat principle. To compare
      costs between groups, confidence intervals for cost differences were computed by
      bias-corrected and accelerated bootstrapping. RESULTS: The mean intervention
      costs, paid by the employer, were 59 euro per participant in the intervention and
      28 euro in the usual care group. Mean total health care and non-health care costs
      per participant were 108 euro in both groups. As to the cost-effectiveness,
      improvement in received information on healthy computer use as well as in their
      work posture and movement was observed at higher costs. With regard to the other
      risk factors, symptoms and sick leave, only small and non-significant effects
      were found. CONCLUSIONS: In this study, the RSI QuickScan intervention programme
      did not prove to be cost-effective from the both the societal and companies'
      perspective and, therefore, this study does not provide a financial reason for
      implementing this intervention. However, with a relatively small investment, the
      programme did increase the number of workers who received information on healthy
      computer use and improved their work posture and movement. TRIAL REGISTRATION: 
      TRIAL REGISTRATION NUMBER: NTR1117.

PMID- 21070622
TI  - Views of junior doctors about whether their medical school prepared them well for
      work: questionnaire surveys.
AB  - BACKGROUND: The transition from medical student to junior doctor in postgraduate
      training is a critical stage in career progression. We report junior doctors'
      views about the extent to which their medical school prepared them for their work
      in clinical practice. METHODS: Postal questionnaires were used to survey the
      medical graduates of 1999, 2000, 2002 and 2005, from all UK medical schools, one
      year after graduation, and graduates of 2000, 2002 and 2005 three years after
      graduation. Summary statistics, chi-squared tests, and binary logistic regression
      were used to analyse the results. The main outcome measure was the level of
      agreement that medical school had prepared the responder well for work. RESULTS:
      Response rate was 63.7% (11610/18216) in year one and 60.2% (8427/13997) in year
      three. One year after graduation, 36.3% (95% CI: 34.6, 38.0) of 1999/2000
      graduates, 50.3% (48.5, 52.2) of 2002 graduates, and 58.2% (56.5, 59.9) of 2005
      graduates agreed their medical school had prepared them well. Conversely, in year
      three agreement fell from 48.9% (47.1, 50.7) to 38.0% (36.0, 40.0) to 28.0%
      (26.2, 29.7). Combining cohorts at year one, percentages who agreed that they had
      been well prepared ranged from 82% (95% CI: 79-87) at the medical school with the
      highest level of agreement to 30% (25-35) at the lowest. At year three the range
      was 70% to 27%. Ethnicity and sex were partial predictors of doctors' level of
      agreement; following adjustment for them, substantial differences between schools
      remained. In years one and three, 30% and 34% of doctors specified that feeling
      unprepared had been a serious or medium-sized problem for them (only 3% in each
      year regarded it as serious). CONCLUSIONS: The vast knowledge base of clinical
      practice makes full preparation impossible. Our statement about feeling prepared
      is simple yet discriminating and identified some substantial differences between
      medical schools. Medical schools need feedback from graduates about elements of
      training that could be improved.

PMID- 21070623
TI  - Discovering hidden relationships between renal diseases and regulated genes
      through 3D network visualizations.
AB  - BACKGROUND: In a recent study, two-dimensional (2D) network layouts were used to
      visualize and quantitatively analyze the relationship between chronic renal
      diseases and regulated genes. The results revealed complex relationships between
      disease type, gene specificity, and gene regulation type, which led to important
      insights about the underlying biological pathways. Here we describe an attempt to
      extend our understanding of these complex relationships by reanalyzing the data
      using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing
      methods. FINDINGS: The 3D network layout (displayed through the 3D viewing
      method) revealed that genes implicated in many diseases (non-specific genes)
      tended to be predominantly down-regulated, whereas genes regulated in a few
      diseases (disease-specific genes) tended to be up-regulated. This new global
      relationship was quantitatively validated through comparison to 1000 random
      permutations of networks of the same size and distribution. Our new finding
      appeared to be the result of using specific features of the 3D viewing method to
      analyze the 3D renal network. CONCLUSIONS: The global relationship between gene
      regulation and gene specificity is the first clue from human studies that there
      exist common mechanisms across several renal diseases, which suggest hypotheses
      for the underlying mechanisms. Furthermore, the study suggests hypotheses for why
      the 3D visualization helped to make salient a new regularity that was difficult
      to detect in 2D. Future research that tests these hypotheses should enable a more
      systematic understanding of when and how to use 3D network visualizations to
      reveal complex regularities in biological networks.

PMID- 21070625
TI  - Drinking in transition: trends in alcohol consumption in Russia 1994-2004.
AB  - BACKGROUND: Heavy alcohol consumption is widespread in Russia, but studying
      changes in drinking during the transition from Communism has been hampered
      previously by the lack of frequent data. This paper uses 1-2 yearly panel data,
      comparing consumption trends with the rapid concurrent changes in economic
      variables (notably around the "Rouble crisis", shortly preceding the 1998 survey
      round), and mortality. METHODS: Data were from 9 rounds (1994-2004) of the 38
      centre Russia Longitudinal Monitoring Survey. Respondents aged over 18 were
      included (>7,000 per round). Trends were measured in alcohol frequency, quantity
      per occasion (by beverage type) and 2 measures of potentially hazardous
      consumption: (i) frequent, heavy spirit drinking (>=80 g per occasion of vodka or
      samogon and >weekly) (ii) consuming samogon (cheap home-distilled spirit). Trends
      in consumption, mean household income and national mortality rates (in the same
      and subsequent 2 years) were compared. Finally, in a subsample of individual male
      respondents present in both the 1996 and 1998 rounds (before and after the
      financial crash), determinants of changes in harmful consumption were studied
      using logistic regression. RESULTS: Frequent, heavy spirit drinking (>80 g each
      time, >=weekly) was widespread amongst men (12-17%) throughout, especially in the
      middle aged and less educated; with the exception of a significant, temporary
      drop to 10% in 1998. From 1996-2000, samogon drinking more than doubled, from 6%
      to 16% of males; despite a decline, levels were significantly higher in 2004 than
      1996 in both sexes. Amongst women, frequent heavy spirit drinking rose non
      significantly to more than 1% during the study. Heavy frequent male drinking and
      mortality in the same year were correlated in lower educated males, but not in
      women. Individual logistic regression in a male subsample showed that between
      1996 and1998, those who lost their employment were more likely to cease frequent,
      heavy drinking; however, men who commenced drinking samogon in 1998 were more
      likely to be rural residents, materially poor, very heavy drinkers or pessimistic
      about their finances. These changes were unexplained by losses to follow-up.
      CONCLUSIONS: Sudden economic decline in late 1990s Russia was associated with a
      sharp, temporary fall in heavy drinking, and a gradual and persistent increase in
      home distilled spirit consumption, with the latter more common amongst
      disadvantaged groups. The correlation between heavy drinking and national
      mortality in lower educated men is interesting, but the timing of RLMS surveys
      late in the calendar year, and the absence of any correlation between drinking
      and the subsequent year's mortality, makes these data hard to interpret.
      Potential study limitations include difficulty in measuring multiple beverages
      consumed per occasion, and not specifically recording "surrogate" (non-beverage)
      alcohols.

PMID- 21070624
TI  - Comparative genomics of prevaccination and modern Bordetella pertussis strains.
AB  - BACKGROUND: Despite vaccination since the 1950s, pertussis has persisted and
      resurged. It remains a major cause of infant death worldwide and is the most
      prevalent vaccine-preventable disease in developed countries. The resurgence of
      pertussis has been associated with the expansion of Bordetella pertussis strains
      with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have
      replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more
      Ptx resulting in increased virulence and immune suppression. To elucidate how B.
      pertussis has adapted to vaccination, we compared genome sequences of two ptxP3
      strains with four strains isolated before and after the introduction vaccination.
      RESULTS: The distribution of SNPs in regions involved in transcription and
      translation suggested that changes in gene regulation play an important role in
      adaptation. No evidence was found for acquisition of novel genes. Modern strains
      differed significantly from prevaccination strains, both phylogenetically and
      with respect to particular alleles. The ptxP3 strains were found to have diverged
      recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1
      strains included SNPs in a number of pathogenicity-associated genes. Further,
      both gene inactivation and reactivation was observed in ptxP3 strains relative to
      modern ptxP1 strains. CONCLUSIONS: Our work suggests that B. pertussis adapted by
      successive accumulation of SNPs and by gene (in)activation. In particular changes
      in gene regulation may have played a role in adaptation.

PMID- 21070626
TI  - Evaluation of unilateral cage-instrumented fixation for lumbar spine.
AB  - BACKGROUND: To investigate how unilateral cage-instrumented posterior lumbar
      interbody fusion (PLIF) affects the three-dimensional flexibility in degenerative
      disc disease by comparing the biomechanical characteristics of unilateral and
      bilateral cage-instrumented PLIF. METHODS: Twelve motion segments in sheep lumbar
      spine specimens were tested for flexion, extension, axial rotation, and lateral
      bending by nondestructive flexibility test method using a nonconstrained testing
      apparatus. The specimens were divided into two equal groups. Group 1 received
      unilateral procedures while group 2 received bilateral procedures. Laminectomy,
      facectomy, discectomy, cage insertion and transpedicle screw insertion were
      performed sequentially after testing the intact status. Changes in range of
      motion (ROM) and neutral zone (NZ) were compared between unilateral and bilateral
      cage-instrumented PLIF. RESULTS: Both ROM and NZ, unilateral cage-instrumented
      PLIF and bilateral cage-instrumented PLIF, transpedicle screw insertion procedure
      did not revealed a significant difference between flexion-extension, lateral
      bending and axial rotation direction except the ROM in the axial rotation. The
      bilateral group's ROM (-1.7 +/- 0. 8) of axial rotation was decreased
      significantly after transpedicle screw insertion procedure in comparison with the
      unilateral group (-0.2 +/- 0.1). In the unilateral cage-instrumented PLIF group,
      the transpedicle screw insertion procedure did not demonstrate a significant
      difference between right and left side in the lateral bending and axial rotation
      direction. CONCLUSIONS: Based on the results of this study, unilateral cage
      instrumented PLIF and bilateral cage-instrumented PLIF have similar stability
      after transpedicle screw fixation in the sheep spine model. The unilateral
      approach can substantially reduce exposure requirements. It also offers the
      biomechanics advantage of construction using anterior column support combined
      with pedicle screws just as the bilateral cage-instrumented group. The unpleasant
      effect of couple motion resulting from inherent asymmetry was absent in the
      unilateral group.

PMID- 21070627
TI  - The G protein regulators EGL-10 and EAT-16, the Gialpha GOA-1 and the G(q)alpha
      EGL-30 modulate the response of the C. elegans ASH polymodal nociceptive sensory
      neurons to repellents.
AB  - BACKGROUND: Polymodal, nociceptive sensory neurons are key cellular elements of
      the way animals sense aversive and painful stimuli. In Caenorhabditis elegans,
      the polymodal nociceptive ASH sensory neurons detect aversive stimuli and release
      glutamate to generate avoidance responses. They are thus useful models for the
      nociceptive neurons of mammals. While several molecules affecting signal
      generation and transduction in ASH have been identified, less is known about
      transmission of the signal from ASH to downstream neurons and about the molecules
      involved in its modulation. RESULTS: We discovered that the regulator of G
      protein signalling (RGS) protein, EGL-10, is required for appropriate avoidance
      responses to noxious stimuli sensed by ASH. As it does for other behaviours in
      which it is also involved, egl-10 interacts genetically with the G(o)/(i)alpha
      protein GOA-1, the G(q)alpha protein EGL-30 and the RGS EAT-16. Genetic,
      behavioural and Ca2(+) imaging analyses of ASH neurons in live animals
      demonstrate that, within ASH, EGL-10 and GOA-1 act downstream of stimulus-evoked
      signal transduction and of the main transduction channel OSM-9. EGL-30 instead
      appears to act upstream by regulating Ca2(+) transients in response to aversive
      stimuli. Analysis of the delay in the avoidance response, of the frequency of
      spontaneous inversions and of the genetic interaction with the diacylglycerol
      kinase gene, dgk-1, indicate that EGL-10 and GOA-1 do not affect signal
      transduction and neuronal depolarization in response to aversive stimuli but act
      in ASH to modulate downstream transmission of the signal. CONCLUSIONS: The ASH
      polymodal nociceptive sensory neurons can be modulated not only in their capacity
      to detect stimuli but also in the efficiency with which they respond to them. The
      Galpha and RGS molecules studied in this work are conserved in evolution and, for
      each of them, mammalian orthologs can be identified. The discovery of their role
      in the modulation of signal transduction and signal transmission of nociceptors
      may help us to understand how pain is generated and how its control can go astray
      (such as chronic pain) and may suggest new pain control therapies.

PMID- 21070629
TI  - The first three-dimensional visualization of a thrombus in transit trapped
      between the leads of a permanent dual-chamber pacemaker: a case report.
AB  - INTRODUCTION: Two-dimensional echocardiography is a useful tool in diagnosing
      cardiac masses. However, the three-dimensional offline reconstruction technique
      of transesophageal echocardiography might be superior to two-dimensional
      transesophageal echocardiography in providing additional information of
      structural details. CASE PRESENTATION: We report the case of a 76-year-old
      Caucasian man with a permanent dual-chamber pacemaker and a worm-like right-heart
      thrombus in transit. Two-dimensional transthoracic echocardiography and two
      dimensional transesophageal echocardiography showed that it was debatable as to
      whether "the worm" was originating from the leads. Offline three-dimensional
      transesophageal echocardiography reconstruction technique proved superior in
      identifying the cardiac mass as a thrombus trapped between the leads of the
      pacemaker. The thrombus was successfully dissolved by systemic heparin therapy.
      CONCLUSIONS: The three-dimensional transesophageal echocardiography is useful and
      effective in patients with implanted pacemakers or defibrillators when other
      closely competing imaging modalities are contraindicated, such as magnetic
      resonance imaging. In patients with pacemakers and trapped thrombus in transit
      for whom surgical therapy might be a high risk, medical therapy seems to offer a
      safer and convincing alternative. Whether the management of right-heart thrombi
      has to be modified due to the presence of pacemaker leads is controversial.

PMID- 21070628
TI  - Quality of life and life circumstances in German myasthenia gravis patients.
AB  - BACKGROUND: Myasthenia gravis (MG) is a chronic neuromuscular disease. Advances
      in medical therapy have continuously increased the life expectancy of MG
      patients, without definitively curing the disease. To analyze life circumstances
      and quality of life (QoL), a large German MG cohort was investigated. METHODS AND
      SAMPLE: In cooperation with the German Myasthenia Association, 2,150 patients
      with confirmed MG were asked to respond to a mailed questionnaire. The
      standardized questions related to demographic data, impairments, therapeutic
      course, use of complementary therapies, illness-related costs, and quality of
      life (SF-36). In total, 1,518 patients participated, yielding a response rate of
      70.6%. The average age was 56.7 years, and the proportion of females 58.6%.
      RESULTS: Despite receiving recommended therapy, many patients still suffered from
      MG-related impairments. In particular, mobility and mental well-being were
      reduced; moreover, quality of life was markedly reduced. Stepwise linear
      regression analysis revealed illness stability, impairments, mental conditions,
      comorbid diseases, and employment to be determinants of QoL. CONCLUSION: Results
      indicate that despite prolonged life expectancy among MG patients, health-related
      quality of life is low. This outcome resulted mainly from impaired mobility and
      depression. Physical and mental well-being might be improved by additional
      therapy options. Additionally, health care resources could be used more
      efficiently in these patients.

PMID- 21070630
TI  - Algorithm-driven artifacts in median polish summarization of microarray data.
AB  - BACKGROUND: High-throughput measurement of transcript intensities using
      Affymetrix type oligonucleotide microarrays has produced a massive quantity of
      data during the last decade. Different preprocessing techniques exist to convert
      the raw signal intensities measured by these chips into gene expression
      estimates. Although these techniques have been widely benchmarked in the context
      of differential gene expression analysis, there are only few examples where their
      performance has been assessed in respect to coexpression-based studies such as
      sample classification. RESULTS: In the present paper we benchmark the three most
      used normalization procedures (MAS5, RMA and GCRMA) in the context of inter-array
      correlation analysis, confirming and extending the finding that RMA and GCRMA
      consistently overestimate sample similarity upon normalization. We determine that
      median polish summarization is responsible for generating a large proportion of
      these over-similarity artifacts. Furthermore, we show that most affected
      probesets show also internal signal disagreement, and tend to be composed by
      individual probes hitting different gene transcripts. We finally provide a
      correction to the RMA/GCRMA summarization procedure that massively reduces inter
      array correlation artifacts, without affecting the detection of differentially
      expressed genes. CONCLUSIONS: We propose tRMA as a modification of RMA to
      normalize microarray experiments for correlation-based analysis.

PMID- 21070632
TI  - Genes regulated by the Escherichia coli SOS repressor LexA exhibit heterogeneous
      expression.
AB  - BACKGROUND: Phenotypic heterogeneity may ensure that a small fraction of a
      population survives environmental perturbations or may result in lysis in a
      subpopulation, to increase the survival of siblings. Genes involved in DNA repair
      and population dynamics play key roles in rapid responses to environmental
      conditions. In Escherichia coli the transcriptional repressor LexA controls a
      coordinated cellular response to DNA damage designated the SOS response.
      Expression of LexA regulated genes, e.g. colicin encoding genes, recA, lexA and
      umuDC, was examined utilizing transcription fusions with the promoterless gfp at
      the single cell level. RESULTS: The investigated LexA regulated genes exhibited
      heterogeneity, as only in a small fraction of the population more intense
      fluorescence was observed. Unlike recA and lexA, the pore forming and nuclease
      colicin activity genes as well as umuDC, exhibited no basal level activity.
      However, in a lexA defective strain high level expression of the gene fusions was
      observed in the large majority of the cells. All of the investigated genes were
      expressed in a recA defective strain, albeit at lower levels, revealing
      expression in the absence of a spontaneous SOS response. In addition, the
      simultaneous expression of cka, encoding the pore forming colicin K, and lexA,
      investigated at the single cell level revealed high level expression of only cka
      in rare individual cells. CONCLUSION: LexA regulated genes exhibit phenotypic
      heterogeneity as high level expression is observed in only a small subpopulation
      of cells. Heterogeneous expression is established primarily by stochastic factors
      and the binding affinity of LexA to SOS boxes.

PMID- 21070633
TI  - The importance of radiological controls of anastomoses after upper
      gastrointestinal tract surgery - a retrospective cohort study.
AB  - INTRODUCTION: This study was designed to analyze whether routine radiological
      controls of anastomoses in the upper gastrointestinal tract an early detection of
      anastomotic leaks. PATIENTS AND METHODS: 135 patients who underwent upper
      gastrointestinal tract surgery were retrospectively analyzed. Patients in the
      first group (n = 55) underwent routine radiological control of the anastomoses.
      In the second group (n = 80) the radiological control was only performed in case
      of clinical symptoms or signs of anastomotic leaks. RESULTS: The incidence of
      anastomotic leaks in the patients seen by us was 5.2%, equivalent to 7 of 135
      patients In Group 1 leaks were seen in 4 of 55 patients (7,2%) in group 2 leaks
      were seen in 3 of 80 (3,8%). The radiological control of the anastomoses with
      contrast swallow showed the leakage in two cases. Twice the results were false
      negative. The sensitivity of computed tomography was 100%. DISCUSSION: Routine
      radiological control of anastomoses with contrast swallow only has low
      sensitivity. This procedure should not be performed routinely any more.The
      radiological control should be used in cases with signs of anastomotic leakage or
      with postoperatively impaired gastrointestinal passage.

PMID- 21070631
TI  - The dopamine beta-hydroxylase -1021C/T polymorphism is associated with the risk
      of Alzheimer's disease in the Epistasis Project.
AB  - BACKGROUND: The loss of noradrenergic neurones of the locus coeruleus is a major
      feature of Alzheimer's disease (AD). Dopamine beta-hydroxylase (DBH) catalyses
      the conversion of dopamine to noradrenaline. Interactions have been reported
      between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of
      the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of
      AD. We therefore examined the associations with AD of the DBH -1021T allele and
      of the above interactions in the Epistasis Project, with 1757 cases of AD and
      6294 elderly controls. METHODS: We genotyped eight single nucleotide
      polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic
      regression models and synergy factor analysis to examine potential interactions
      and associations with AD. RESULTS: We found that the presence of the -1021T
      allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06
      1.4, p = 0.005). This association was nearly restricted to men < 75 years old:
      odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the
      presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy
      factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North
      Europe and North Spain. CONCLUSIONS: Extensive, previous evidence (reviewed here)
      indicates an important role for noradrenaline in the control of inflammation in
      the brain. Thus, the -1021T allele with presumed low activity may be associated
      with misregulation of inflammation, which could contribute to the onset of AD. We
      suggest that such misregulation is the predominant mechanism of the association
      we report here.

PMID- 21070634
TI  - Age-dependent changes in TDP-43 levels in a mouse model of Alzheimer disease are
      linked to Abeta oligomers accumulation.
AB  - BACKGROUND: Transactive response DNA-binding protein 43 (TDP-43) is the
      pathological protein found in frontotemporal lobar degeneration with ubiquitin
      positive inclusions and in amyotrophic lateral sclerosis. In diseased tissue, TDP
      43 translocates from its physiological nuclear location into the cytoplasm, where
      it accumulates. Additionally, C-terminal fragments of TDP-43 accumulate in
      affected brain regions and are sufficient to cause TDP-43 mislocalization and
      cytoplasmic accumulation in vitro. TDP-43 also accumulates in 30% of Alzheimer
      disease (AD) cases, a finding that has been highly reproducible. The role of TDP
      43 in AD and its relation with Abeta and tau pathology, the two neuropathological
      hallmarks of AD, remains to be elucidated. RESULTS: Here we show that levels of
      TDP-43 and its ~35 kDa C-terminal fragment are significantly increased in the
      3*Tg-AD mice, an animal model of AD that develops an age-dependent cognitive
      decline linked to the accumulation of Abeta and tau. We also report that the
      levels of TDP-43 and its C-terminal fragment correlate with the levels of soluble
      Abeta oligomers, which play a key role in AD pathogenesis. Notably, genetically
      reducing Abeta42 production restores the levels of TDP-43 and its ~35 kDa C
      terminal fragment to control levels. CONCLUSIONS: These data suggest a possible
      relation between Abeta oligomers and TDP-43.

PMID- 21070635
TI  - First international summit on fibrosis in intestinal inflammation: mechanisms and
      biological therapies.
AB  - The first meeting dedicated to intestinal fibrosis, entitled The First
      International Summit on Fibrosis in Intestinal Inflammation: Mechanisms and
      Biological Therapies, was held in Cleveland, Ohio, USA, on 28-29 September 2010.
      Intestinal fibrosis is a complication of inflammatory conditions affecting the
      small and large bowel and often results in serious clinical consequences. Despite
      its clinical importance, the study of inflammation-driven intestinal fibrosis has
      received very limited attention. This explains why so little is known about its
      pathophysiology and the lack of significant therapeutic advances, in contrast
      with the recent success achieved in controlling gut inflammation with biological
      agents. The meeting covered most aspects directly relevant to intestinal
      fibrosis, including gut inflammation; cellular and molecular mechanisms of
      intestinal fibrogenesis; new clinical, diagnostic and prognostic tests and novel
      therapeutic approaches.

PMID- 21070636
TI  - Reference left atrial dimensions and volumes by steady state free precession
      cardiovascular magnetic resonance.
AB  - BACKGROUND: Left atrial (LA) size is related to cardiovascular morbidity and
      mortality. Cardiovascular magnetic resonance (CMR) provides high quality images
      of the left atrium with high temporal resolution steady state free precession
      (SSFP) cine sequences. We used SSFP cines to define normal ranges for LA volumes
      and dimensions relative to gender, age and body surface area (BSA), and examine
      the relative value of 2D atrial imaging techniques in patients.For definition of
      normal ranges of LA volume we studied 120 healthy subjects after careful
      exclusion of cardiovascular abnormality (60 men, 60 women; 20 subjects per age
      decile from 20 to 80 years). Data were generated from 3-dimensional modeling,
      including tracking of the atrioventricular ring motion and time-volume curves
      analysis. For definition of the best 2D images-derived predictors of LA
      enlargement, we studied 120 patients (60 men, 60 women; age range 20 to 80 years)
      with a clinical indication for CMR. RESULTS: In the healthy subjects, age was
      associated with LA 4-chamber transverse and 3-chamber anteroposterior diameters,
      but not with LA volume. Gender was an independent predictor of most absolute LA
      dimensions and volume, but following normalization to BSA, some associations
      became non-significant. CMR normal ranges were modeled and are tabled for
      clinical use with normalization, where appropriate, for BSA and gender and
      display of parameter variation with age. The best 2D predictors of LA volume were
      the 2-chamber area and 3-chamber area (both r = 0.90, p < 0.001). CONCLUSIONS:
      These CMR data show that LA dimensions and volume in healthy, individuals vary
      significantly by BSA, with lesser effects of age and gender.

PMID- 21070637
TI  - Neck dissection and post-operative chemotherapy with dimethyl triazeno imidazole
      carboxamide and cisplatin protocol are useful for oral mucosal melanoma.
AB  - BACKGROUND: Oral mucosal melanoma (OMM) is a clinically rare disease with poor
      prognosis. Various treatment methods have been investigated with the aim of
      improving the prognosis. This study aimed to analyze the data of a single
      institution in the management of OMM. METHODS: A total of 78 consecutive OMM
      patients were included in this retrospective study. The intraoral lesion was
      treated either by cryotherapy, surgery or both; the neck was treated by neck
      dissection or observation; post-operative chemotherapy with dimethyl triazeno
      imidazole carboxamide and cisplatin was performed in some patients. The Kaplan
      Meier method was used for statistical analysis. RESULTS: Among the 78 patients,
      there were 50 males and 28 females with an average age of 53.8 years (ranging
      from 27 to 85 years). The most common sites of OMM were the hard palate and
      gingiva. The main cause of death in OMM was distant metastasis. No significant
      difference was found between the intraoral/cervical lesion recurrence/post
      operative distant metastasis and the intraoral lesion site/biopsy
      method/treatment method. The metastasis rate of cervical lymph node was high in
      the OMM patients, even in the patients with clinically negative necks. Cervical
      lesion recurrence was correlated with N stage and intraoral lesion recurrence.
      The survival period was longer in the patients with T3 staging, clinical stage
      III disease, with post-operative chemotherapy and without post-operative distant
      metastasis when compared to those patients with T4a staging, clinical stage IV
      disease, without post-operative chemotherapy and with post-operative distant
      metastasis. CONCLUSIONS: Radical surgery including wide intraoral resection and
      neck dissection is recommended for OMM patients. Post-operative chemotherapy may
      also be beneficial for both primary and recurrent OMM patients.

PMID- 21070638
TI  - Contemporary temperature-driven divergence in a Nordic freshwater fish under
      conditions commonly thought to hinder adaptation.
AB  - BACKGROUND: Evaluating the limits of adaptation to temperature is important given
      the IPCC-predicted rise in global temperatures. The rate and scope of
      evolutionary adaptation can be limited by low genetic diversity, gene flow, and
      costs associated with adaptive change. Freshwater organisms are physically
      confined to lakes and rivers, and must therefore deal directly with climate
      variation and change. In this study, we take advantage of a system characterised
      by low genetic variation, small population size, gene flow and between-trait
      trade-offs to study how such conditions affect the ability of a freshwater fish
      to adapt to climate change. We test for genetically-based differences in
      developmental traits indicating local adaptation, by conducting a common-garden
      experiment using embryos and larvae from replicate pairs of sympatric grayling
      demes that spawn and develop in natural cold and warm water, respectively. These
      demes have common ancestors from a colonization event 22 generations ago.
      Consequently, we explore if diversification may occur under severely constraining
      conditions. RESULTS: We found evidence for divergence in ontogenetic rates. The
      divergence pattern followed adaptation predictions as cold-deme individuals
      displayed higher growth rates and yolk conversion efficiency than warm-deme
      individuals at the same temperature. The cold-deme embryos had a higher rate of
      muscle mass development. Most of the growth- and development differences occurred
      prior to hatch. The divergence was probably not caused by genetic drift as there
      was a strong degree of parallelism in the divergence pattern and because
      phenotypic differentiation (Q(ST)) was larger than estimated genetic drift levels
      (microsatellite F(ST)) between demes from different temperature groups. We also
      document that these particular grayling populations cannot develop successfully
      at temperatures above 12 degrees C, whereas other European populations can, and
      that increasing the muscle mass development rate comes at the cost of some
      skeletal trait development rates. CONCLUSIONS: This study shows that genetically
      based phenotypic divergence can prevail even under conditions of low genetic
      variation and ongoing gene flow. Furthermore, population-specific maximum
      development temperatures along with musculoskeletal developmental trade-offs may
      constrain adaptation.

PMID- 21070639
TI  - Design of the Quality of Life in Motion (QLIM) study: a randomized controlled
      trial to evaluate the effectiveness and cost-effectiveness of a combined physical
      exercise and psychosocial training program to improve physical fitness in
      children with cancer.
AB  - BACKGROUND: Childhood cancer and its treatment have considerable impact on a
      child's physical and mental wellbeing. Especially long-term administration of
      chemotherapy and/or radiotherapy impairs physical fitness both during and after
      therapy, when children often present with muscle weakness and/or low
      cardiorespiratory fitness. Physical exercise can improve these two elements of
      physical fitness, but the positive effects of physical exercise might be further
      increased when a child's wellbeing is simultaneously enhanced by psychosocial
      training. Feeling better may increase the willingness and motivation to engage in
      sports activities. Therefore, this multi-centre study evaluates the short and
      long-term changes in physical fitness of a child with a childhood malignancy,
      using a combined physical exercise and psychosocial intervention program,
      implemented during or shortly after treatment. Also examined is whether positive
      effects on physical fitness reduce inactivity-related adverse health problems,
      improve quality of life, and are cost-effective. METHODS: This multi-centre
      randomized controlled trial compares a combined physical and psychosocial
      intervention program for children with cancer, with care as usual (controls).
      Children with cancer (aged 8-18 years) treated with chemotherapy and/or
      radiotherapy, and who are no longer than 1 year post-treatment, are eligible for
      participation. A total of 100 children are being recruited from the paediatric
      oncology/haematology departments of three Dutch university medical centres.
      Patients are stratified according to pubertal stage (girls: age <=10 or >10
      years; boys: <=11 or >11 years), type of malignancy (haematological or solid
      tumour), and moment of inclusion into the study (during or after treatment), and
      are randomly assigned to the intervention or control group. DISCUSSION: Childhood
      cancer patients undergoing long-term cancer therapy may benefit from a combined
      physical exercise and psychosocial intervention program since it may maintain or
      enhance their physical fitness and increase their quality of life. However, the
      feasibility, patient need, and effectiveness of such a program should be
      established before the program can be implemented as part of standard care. TRIAL
      REGISTRATION NUMBER: NTR1531 (The Netherlands National Trial Register).

PMID- 21070640
TI  - FITBAR: a web tool for the robust prediction of prokaryotic regulons.
AB  - BACKGROUND: The binding of regulatory proteins to their specific DNA targets
      determines the accurate expression of the neighboring genes. The in silico
      prediction of new binding sites in completely sequenced genomes is a key aspect
      in the deeper understanding of gene regulatory networks. Several algorithms have
      been described to discriminate against false-positives in the prediction of new
      binding targets; however none of them has been implemented so far to assist the
      detection of binding sites at the genomic scale. RESULTS: FITBAR (Fast
      Investigation Tool for Bacterial and Archaeal Regulons) is a web service designed
      to identify new protein binding sites on fully sequenced prokaryotic genomes.
      This tool consists in a workbench where the significance of the predictions can
      be compared using different statistical methods, a feature not found in existing
      resources. The Local Markov Model and the Compound Importance Sampling algorithms
      have been implemented to compute the P-value of newly discovered binding sites.
      In addition, FITBAR provides two optimized genomic scanning algorithms using
      either log-odds or entropy-weighted position-specific scoring matrices. Other
      significant features include the production of a detailed genomic context map for
      each detected binding site and the export of the search results in spreadsheet
      and portable document formats. FITBAR discovery of a high affinity Escherichia
      coli NagC binding site was validated experimentally in vitro as well as in vivo
      and published. CONCLUSIONS: FITBAR was developed in order to allow fast, accurate
      and statistically robust predictions of prokaryotic regulons. This feature
      constitutes the main advantage of this web tool over other matrix search programs
      and does not impair its performance. The web service is available at
      http://archaea.u-psud.fr/fitbar.

PMID- 21070641
TI  - Inequalities in health and health service utilisation among reproductive age
      women in St. Petersburg, Russia: a cross-sectional study.
AB  - BACKGROUND: Russian society has faced dramatic changes in terms of social
      stratification since the collapse of the Soviet Union. During this time,
      extensive reforms have taken place in the organisation of health services,
      including the development of the private sector. Previous studies in Russia have
      shown a wide gap in mortality between socioeconomic groups. There are just a few
      studies on health service utilisation in post-Soviet Russia and data on
      inequality of health service use are limited. The aim of the present study was to
      analyse health (self-rated health and self-reported chronic diseases) and health
      care utilisation patterns by socioeconomic status (SES) among reproductive age
      women in St. Petersburg. METHODS: The questionnaire survey was conducted in 2004
      (n = 1147), with a response rate of 67%. Education and income were used as
      dimensions of SES. The association between SES and health and use of health
      services was assessed by logistic regression, adjusting for age. RESULTS: As
      expected low SES was associated with poor self-rated health (education: OR =
      1.48; personal income: OR = 1.42: family income: OR = 2.31). University education
      was associated with use of a wider range of outpatient medical services and
      increased use of the following examinations: Pap smear (age-adjusted OR = 2.06),
      gynaecological examinations (age-adjusted OR = 1.62) and mammography among older
      (more than 40 years) women (age-adjusted OR = 1.98). Personal income had similar
      correlations, but family income was related only to the use of mammography among
      older women. CONCLUSIONS: Our study suggests a considerable inequality in health
      and utilisation of preventive health service among reproductive age women.
      Therefore, further studies are needed to identify barriers to health promotion
      resources.

PMID- 21070642
TI  - Myostatin genotype regulates muscle-specific miRNA expression in mouse pectoralis
      muscle.
AB  - BACKGROUND: Loss of functional Myostatin results in a dramatic increase in
      skeletal muscle mass. It is unknown what role miRNAs play in Myostatin mediated
      repression of skeletal muscle mass. We hypothesized that Myostatin genotype would
      be associated with the differential expression of miRNAs in skeletal muscle.
      FINDINGS: Loss of functional Myostatin resulted in a significant increase (p <
      .001) in miR-1, miR-133a, miR-133b, and miR-206 expression. In contrast,
      Myostatin genotype had no effect (P > .2) on miR-24 expression level. Myostatin
      genotype did not affect the expression level of MyoD or Myogenin (P > 0.5).
      CONCLUSIONS: Myostatin may regulates the expression of miRNAs such as miR-133a,
      miR-133b, miR-1, and miR-206 in skeletal muscle as it has been observed that the
      expression of those miRNAs are significantly higher in myostatin null mice
      compared to wild type and heterozygous mice. In contrast, expression of myogenic
      factors such as MyoD or Myogenin has not been affected by myostatin in the muscle
      tissue.

PMID- 21070643
TI  - Partnership work between Public Health and Health Psychology: introduction to a
      novel training programme.
AB  - BACKGROUND: Public health services implement individual, community and population
      level interventions to change health behaviours, improve healthy life expectancy
      and reduce health inequalities. Understanding and changing health behaviour is
      complex. Integrating behaviour change theory and evidence into interventions has
      the potential to improve services. METHODS: Health Psychologists apply evidence
      and theories aimed at understanding and changing health behaviour. A Scottish
      programme is piloting the training of Health Psychologists within NHS contexts to
      address prominent public health challenges. RESULTS: This article outlines the
      details of this novel programme. Two projects are examined to illustrate the
      potential of partnership working between public health and health psychology.
      CONCLUSION: In order to develop and improve behaviour change interventions and
      services, public health planners may want to consider developing and using the
      knowledge and skills of Health Psychologists. Supporting such training within
      public health contexts is a promising avenue to build critical NHS internal mass
      to tackle the major public health challenges ahead.

PMID- 21070644
TI  - Determinants of delay in malaria treatment-seeking behaviour for under-five
      children in south-west Ethiopia: a case control study.
AB  - BACKGROUND: Prompt diagnosis and timely treatment of malaria within 24 hours
      after onset of first symptoms can reduce illness progression to severe stages and
      therefore, decrease mortality. The reason why mothers/caretakers delay in malaria
      diagnosis and treatment for under-five children is not well studied in Ethiopia.
      The objective of this study was to assess determinants of malaria treatment delay
      in under-five children in three districts of south-west Ethiopia. METHODS: A case
      control study was conducted from March 15 to April 20, 2010. Cases were under
      five children who had clinical malaria and sought treatment after 24 hours of
      developing sign and symptom, and controls were under-five children who had
      clinical malaria and sought treatment within 24 hours of developing sign and
      symptom of malaria. Data were collected by trained enumerators using structured
      questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using
      SPSS version 16.0. To identify determinants, multiple logistic regression was
      done. RESULTS: A total of 155 mothers of cases and 155 mothers of controls were
      interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41,
      95% CI: 1.39, 8.34), who complained about the side effects of anti-malarial drugs
      (OR = 4.96, 95% CI: 1.21, 20.36), who had no history of child death (OR = 3.50,
      95% CI: 1.82, 6.42) and who complained about the higher cost of transportation to
      reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45) were more likely to
      be late for the treatment of malaria in under-five children. CONCLUSION:
      Effective malaria control programmes should address reducing delayed presentation
      of children for treatment. Efforts to reduce delay should address transport cost,
      decentralization of services and increasing awareness of the community on early
      diagnosis and treatment.

PMID- 21070645
TI  - Global genome analysis of the shikimic acid pathway reveals greater gene loss in
      host-associated than in free-living bacteria.
AB  - BACKGROUND: A central tenet in biochemistry for over 50 years has held that
      microorganisms, plants and, more recently, certain apicomplexan parasites
      synthesize essential aromatic compounds via elaboration of a complete shikimic
      acid pathway, whereas metazoans lacking this pathway require a dietary source of
      these compounds. The large number of sequenced bacterial and archaean genomes now
      available for comparative genomic analyses allows the fundamentals of this
      contention to be tested in prokaryotes. Using Hidden Markov Model profiles (HMM
      profiles) to identify all known enzymes of the pathway, we report the presence of
      genes encoding shikimate pathway enzymes in the hypothetical proteomes
      constructed from the genomes of 488 sequenced prokaryotes. RESULTS: Amongst free
      living prokaryotes most Bacteria possess, as expected, genes encoding a complete
      shikimic acid pathway, whereas of the culturable Archaea, only one was found to
      have a complete complement of recognisable enzymes in its predicted proteome. It
      may be that in the Archaea, the primary amino-acid sequences of enzymes of the
      pathway are highly divergent and so are not detected by HMM profiles.
      Alternatively, structurally unrelated (non-orthologous) proteins might be
      performing the same biochemical functions as those encoding recognized genes of
      the shikimate pathway. Most surprisingly, 30% of host-associated (mutualistic,
      commensal and pathogenic) bacteria likewise do not possess a complete shikimic
      acid pathway. Many of these microbes show some degree of genome reduction,
      suggesting that these host-associated bacteria might sequester essential aromatic
      compounds from a parasitised host, as a 'shared metabolic adaptation' in
      mutualistic symbiosis, or obtain them from other consorts having the complete
      biosynthetic pathway. The HMM results gave 84% agreement when compared against
      data in the highly curated BioCyc reference database of genomes and metabolic
      pathways. CONCLUSIONS: These results challenge the conventional belief that the
      shikimic acid pathway is universal and essential in prokaryotes. The
      possibilities that non-orthologous enzymes catalyse reactions in this pathway
      (especially in the Archaea), or that there exist specific uptake mechanisms for
      the acquisition of shikimate intermediates or essential pathway products, warrant
      further examination to better understand the precise metabolic attributes of host
      beneficial and pathogenic bacteria.

PMID- 21070646
TI  - "Pee-in-a-Pot": acceptability and uptake of on-site chlamydia screening in a
      student population in the Republic of Ireland.
AB  - BACKGROUND: The aim of the study was to explore the acceptability and uptake of
      on-campus screening using a youth friendly approach in two Third Level higher
      education institutions (HEIs). This study is part of wider research exploring the
      optimal setting for chlamydia screening in Ireland. METHODS: Male and female
      students were given the opportunity to take a free anonymous test for chlamydia
      during a one week programme of "pee-in-a-pot" days at two HEI campuses in the
      West of Ireland. The study was set up after extensive consultation with the two
      HEIs and advertised on the two campuses using a variety of media in the two weeks
      preceding the screening days. Screening involved the provision and distribution
      of testing packs at communal areas and in toilet facilities. In Ireland,
      chlamydia notifications are highest amongst 20-29 year olds and hence the
      screening criterion was aimed at 18-29 year olds. Urine samples were tested using
      a nucleic acid amplification test (NAAT). Following the screening days,
      qualitative in-depth interviews were conducted with participants about their
      experiences of the event. RESULTS: Out of 1,249 test kits distributed in two
      HEIs, 592 specimens were collected giving a return rate of 47.5%. Tests excluded
      (54) were due to labelling errors or ineligibility of participants' age. Two
      thirds of those tested were females and the mean age was 21 years. Overall, 3.9%
      (21/538) of participants tested positive, 5% (17/336) among females and 2%
      (4/191) among males. Participant interviews identified factors which enhanced
      student participation such as anonymity, convenience, accessibility of testing,
      and the informal and non-medical approach to testing. CONCLUSIONS: Screening for
      chlamydia using on-campus "pee-in-a-pot" days is an acceptable strategy in this
      population. This model can detect and treat asymptomatic cases of chlamydia and
      avoid many of the barriers associated with testing for sexually transmitted
      infections (STIs) in clinical settings.

PMID- 21070648
TI  - Eosinophilic infiltrate in a patient with severe Legionella pneumonia as a
      levofloxacin-related complication: a case report.
AB  - INTRODUCTION: Legionella pneumonia can appear with different levels of severity
      and it can often present with complications such as acute respiratory distress
      syndrome. CASE PRESENTATION: We report the case of a 44-year-old Caucasian man
      with Legionella pneumonia with successive development of severe acute respiratory
      distress syndrome. During his stay in intensive care the clinical and
      radiological situation of the previously observed acute respiratory distress
      syndrome unexpectedly worsened due to acute pulmonary eosinophilic infiltrate of
      iatrogenic origin. CONCLUSION: Levofloxacin treatment caused the occurrence of
      acute eosinophilic infiltrate. Diagnosis was possible following bronchoscopic
      examination using bronchoaspirate and transbronchial biopsy.

PMID- 21070647
TI  - Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a
      case report.
AB  - Cellular therapy for spinal cord injury (SCI) is overviewed focusing on bone
      marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem
      cells. A case is made for the possibility of combining cell types, as well as for
      allogeneic use. We report the case of 29 year old male who suffered a crush
      fracture of the L1 vertebral body, lacking lower sensorimotor function, being a
      score A on the ASIA scale. Stem cell therapy comprised of intrathecal
      administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and
      umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after
      injury. Cell administration was well tolerated with no adverse effects observed.
      Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS.
      Recovery of muscle, bowel and sexual function was noted, along with a decrease in
      ASIA score to "D". This case supports further investigation into allogeneic-based
      stem cell therapies for SCI.

PMID- 21070649
TI  - 25-Hydroxycholesterol exerts both a cox-2-dependent transient proliferative
      effect and cox-2-independent cytotoxic effect on bovine endothelial cells in a
      time- and cell-type-dependent manner.
AB  - BACKGROUND: 25-hydroxycholesterol (25-OHC) is a product of oxidation of dietary
      cholesterol present in human plasma. 25-OHC and other oxidized forms of
      cholesterol are implicated in modulating inflammatory responses involved in
      development of atherosclerosis and colon carcinogenesis. METHODS: Primary
      lymphatic, venous and arterial endothelial cells isolated from bovine mesentery
      (bmLEC, bmVEC, bmAEC) were treated with 25-OHC and tested for several different
      cellular parameters. RESULTS: We found 25-OHC to be a potent inducer of
      cyclooxygenase-2 (Cox-2, prostaglandin G-H synthase-2) expression in bovine
      mesenteric lymphatic, venous, and arterial endothelial cells. The induction of
      Cox-2 expression in endothelial cells by 25-OHC led to an initial increase in
      cellular proliferation that was inhibited by the Cox-2 selective inhibitor
      celecoxib (Celebrex). Prolonged exposure to 25-OHC was cytotoxic. Furthermore,
      endothelial cells induced to express Cox-2 by 25-OHC were more sensitive to the
      effects of the Cox-2 selective inhibitor celecoxib (Celebrex). These results
      suggest that some effects of 25-OHC on cells may be dependent on Cox-2 enzymatic
      activity. CONCLUSIONS: Cox-2 dependent elevating effects of 25-OHC on endothelial
      cell proliferation was transient. Prolonged exposure to 25-OHC caused cell death
      and enhanced celecoxib-induced cell death in a cell-type dependent manner. The
      lack of uniform response by the three endothelial cell types examined suggests
      that our model system of primary cultures of bmLECs, bmVECs, and bmAECs may aid
      the evaluation of celecoxib in inhibiting proliferation of different types of
      tumour-associated endothelial cells.

PMID- 21070650
TI  - Post-load hyperglycemia as an important predictor of long-term adverse cardiac
      events after acute myocardial infarction: a scientific study.
AB  - BACKGROUND: Diabetes mellitus (DM) and impaired glucose tolerance (IGT) are risk
      factors for acute myocardial infarction (AMI). However, it is unknown whether
      hyperglycemic state is associated with increased major adverse cardiovascular
      events (MACE) after AMI. In this study, we evaluated the relationship between
      glucometabolic status and MACE in patients after AMI, and determined the critical
      level of 2 h post-load plasma glucose that may be used to predict MACE. METHODS:
      AMI patients (n = 422) were divided into 4 groups as follows: normal glucose
      tolerance (NGT) group, IGT group, newly diagnosed DM (NDM) group, and previously
      known DM (PDM) group. MACE of the 4 groups were compared for 2 years from AMI
      onset. RESULTS: The NDM group had a significantly higher event rate than the IGT
      and NGT groups and had a similar event rate curve to PDM group. The logistic
      models analyses revealed that 2 h post-load plasma glucose values of >=160 mg/dL
      was the only independent predictor of long-term MACE after AMI (p = 0.028, OR:
      1.85, 95% CI: 1.07-3.21). The 2-year cardiac event rate of patients with a 2 h
      post-load hyperglycemia of >=160 mg/dL was significantly higher than that of
      patients with 2 h post-load glucose of <160 mg/dL (32.2% vs. 19.8%, p < 0.05) and
      was similar to that of PDM group (37.4%, p = 0.513). CONCLUSIONS: NDM increases
      the risk of MACE after AMI as does PDM. Particularly, post-AMI patients with a 2
      h post-load hyperglycemia >=160 mg/dL may need adjunctive therapy after AMI.

PMID- 21070651
TI  - The LabelHash algorithm for substructure matching.
AB  - BACKGROUND: There is an increasing number of proteins with known structure but
      unknown function. Determining their function would have a significant impact on
      understanding diseases and designing new therapeutics. However, experimental
      protein function determination is expensive and very time-consuming.
      Computational methods can facilitate function determination by identifying
      proteins that have high structural and chemical similarity. RESULTS: We present
      LabelHash, a novel algorithm for matching substructural motifs to large
      collections of protein structures. The algorithm consists of two phases. In the
      first phase the proteins are preprocessed in a fashion that allows for instant
      lookup of partial matches to any motif. In the second phase, partial matches for
      a given motif are expanded to complete matches. The general applicability of the
      algorithm is demonstrated with three different case studies. First, we show that
      we can accurately identify members of the enolase superfamily with a single
      motif. Next, we demonstrate how LabelHash can complement SOIPPA, an algorithm for
      motif identification and pairwise substructure alignment. Finally, a large
      collection of Catalytic Site Atlas motifs is used to benchmark the performance of
      the algorithm. LabelHash runs very efficiently in parallel; matching a motif
      against all proteins in the 95% sequence identity filtered non-redundant Protein
      Data Bank typically takes no more than a few minutes. The LabelHash algorithm is
      available through a web server and as a suite of standalone programs at
      http://labelhash.kavrakilab.org. The output of the LabelHash algorithm can be
      further analyzed with Chimera through a plugin that we developed for this
      purpose. CONCLUSIONS: LabelHash is an efficient, versatile algorithm for large
      scale substructure matching. When LabelHash is running in parallel, motifs can
      typically be matched against the entire PDB on the order of minutes. The
      algorithm is able to identify functional homologs beyond the twilight zone of
      sequence identity and even beyond fold similarity. The three case studies
      presented in this paper illustrate the versatility of the algorithm.

PMID- 21070652
TI  - Differential gene expression in nearly isogenic lines with QTL for partial
      resistance to Puccinia hordei in barley.
AB  - BACKGROUND: The barley-Puccinia hordei (barley leaf rust) pathosystem is a model
      for investigating partial disease resistance in crop plants and genetic mapping
      of phenotypic resistance has identified several quantitative trait loci (QTL) for
      partial resistance. Reciprocal QTL-specific near-isogenic lines (QTL-NILs) have
      been developed that combine two QTL, Rphq2 and Rphq3, the largest effects
      detected in a recombinant-inbred-line (RIL) population derived from a cross
      between the super-susceptible line L94 and partially-resistant line Vada. The
      molecular mechanism underpinning partial resistance in these QTL-NILs is unknown.
      RESULTS: An Agilent custom microarray consisting of 15,000 probes derived from
      barley consensus EST sequences was used to investigate genome-wide and QTL
      specific differential expression of genes 18 hours post-inoculation (hpi) with
      Puccinia hordei. A total of 1,410 genes were identified as being significantly
      differentially expressed across the genome, of which 55 were accounted for by the
      genetic differences defined by QTL-NILs at Rphq2 and Rphq3. These genes were
      predominantly located at the QTL regions and are, therefore, positional
      candidates. One gene, encoding the transcriptional repressor Ethylene-Responsive
      Element Binding Factor 4 (HvERF4) was located outside the QTL at 71 cM on
      chromosome 1H, within a previously detected eQTL hotspot for defence response.
      The results indicate that Rphq2 or Rphq3 contains a trans-eQTL that modulates
      expression of HvERF4. We speculate that HvERF4 functions as an intermediate that
      conveys the response signal from a gene(s) contained within Rphq2 or Rphq3 to a
      host of down-stream defense responsive genes. Our results also reveal that barley
      lines with extreme or intermediate partial resistance phenotypes exhibit a
      profound similarity in their spectrum of Ph-responsive genes and that hormone
      related signalling pathways are actively involved in response to Puccinia hordei.
      CONCLUSIONS: Differential gene expression between QTL-NILs identifies genes
      predominantly located within the target region(s) providing both transcriptional
      and positional candidate genes for the QTL. Genetically mapping the
      differentially expressed genes relative to the QTL has the potential to discover
      trans-eQTL mediated regulatory relays initiated from genes within the QTL
      regions.

PMID- 21070653
TI  - Novel dual-function CellDetect(r) staining technology: wedding morphology and
      tinctorial discrimination to detect cervical neoplasia.
AB  - BACKGROUND: A persistent goal of oncologic histochemistry is to microscopically
      identify neoplasia tinctorially. Consequently, the newly developed CellDetect(r)
      staining technology, that appears to exhibit this property, warrants clinical
      evaluation. The objective of this study was to compare the diagnostic results
      using CellDetect(r) to the outcomes of standard microscopic examination based on
      hematoxylin and eosin (H&E) staining for the recognition of different squamous
      epithelial phenotypes of the uterine cervix. METHODS: Pairs of adjacent sections
      were made from 60 cervical biopsy cases that were diagnosed originally as either
      normal or neoplastic (CIN, SCC). One section of the pair was stained for H&E; the
      second section, with CellDetect(r). Based on the examination of these pairs by
      two experienced pathologists, we investigated the following issues:(1) diagnostic
      agreement between the pathologists on each pair; (2) agreement between H&E and
      CellDetect(r) for each pair (3) tinctorial characteristics in micro-regions (n =
      130) evaluated as either normal, reactive or neoplastic. RESULTS: Qualitatively,
      CellDetect(r)-stained preparations displayed cyto-morphological detail comparable
      to H&E images. Tinctorially, non-neoplastic cells appeared green/blue when
      stained withCellDetect(r), contrasting with cytologically neoplastic foci, where
      cells of every grade were red/magenta in color. Due to these tinctorial
      characteristics, even small foci of neoplasia could be readily distinguished that
      were inconspicuous on H&E at low magnification. In some instances, this prompted
      re-examination of the H&E and revision of the diagnosis. Quantitatively, we found
      that despite diagnostic variation between pathologists, in about 3% of the cases,
      each pathologist made the same diagnosis regardless of whether CellDetect(r) or
      H&E was used, i.e. there was 100% self-agreement for each pathologist between
      stains. Particularly noteworthy was the finding of a 0% false negative rate,
      coupled with a 10-15% false positive rate. Regarding specificity, the performance
      in reactive squamous processes was similar to that observed for morphologically
      normal squamous epithelium. CONCLUSIONS: In this first order assessment of
      clinical applicability, CellDetect(r) staining technology was at least comparable
      to results using H&E, and perhaps surperior. CellDetect(r) provided a uniquely
      useful tinctorial clue for the detection of neoplasia, which exhibited an
      impressive 0% false negative rate. A more extensive, blinded study is needed to
      confirm these promising findings.

PMID- 21070654
TI  - Are MRI high-signal changes of alar and transverse ligaments in acute whiplash
      injury related to outcome?
AB  - BACKGROUND: Upper neck ligament high-signal changes on magnetic resonance imaging
      (MRI) have been found in patients with whiplash-associated disorders (WAD) but
      also in non-injured controls. The clinical relevance of such changes is
      controversial. Their prognostic role has never been evaluated. The purpose of
      this study was to examine if alar and transverse ligament high-signal changes on
      MRI immediately following the car accident are related to outcome after 12 months
      for patients with acute WAD grades 1-2. METHODS: Within 13 days after a car
      accident, 114 consecutive acute WAD1-2 patients without prior neck injury or
      prior neck problems underwent upper neck high-resolution proton-weighted MRI.
      High-signal changes of the alar and transverse ligaments were graded 0-3. A
      questionnaire including the impact of event scale for measuring posttraumatic
      stress response and questions on patients' expectations of recovery provided
      clinical data at injury. At 12 months follow-up, 111 (97.4%) patients completed
      the Neck Disability Index (NDI) and an 11-point numeric rating scale (NRS-11) on
      last week neck pain intensity. Factors potentially related to these outcomes were
      assessed using multiple logistic regression analyses. RESULTS: Among the 111
      responders (median age 29.8 years; 63 women), 38 (34.2%) had grades 2-3 alar
      ligament changes and 25 (22.5%) had grades 2-3 transverse ligament changes at
      injury. At 12 months follow-up, 49 (44.1%) reported disability (NDI > 8) and 23
      (20.7%) neck pain (NRS-11 > 4). Grades 2-3 ligament changes in the acute phase
      were not related to disability or neck pain at 12 months. More severe
      posttraumatic stress response increased the odds for disability (odds ratio 1.46
      per 10 points on the impact of event scale, p = 0.007) and so did low
      expectations of recovery (odds ratio 4.66, p = 0.005). CONCLUSIONS: High-signal
      changes of the alar and transverse ligaments close after injury did not affect
      outcome for acute WAD1-2 patients without previous neck problems. High-resolution
      upper neck MRI has limited value for the initial examination and follow-up of
      such patients.

PMID- 21070655
TI  - Malaria transmission and insecticide resistance of Anopheles gambiae in
      Libreville and Port-Gentil, Gabon.
AB  - BACKGROUND: Urban malaria is a major health priority for civilian and militaries
      populations. A preliminary entomologic study has been conducted in 2006-2007, in
      the French military camps of the two mains towns of Gabon: Libreville and Port
      Gentil. The aim was to assess the malaria transmission risk for troops. METHODS:
      Mosquitoes sampled by human landing collection were identified morphologically
      and by molecular methods. The Plasmodium falciparum circumsporozoite (CSP)
      indexes were measured by ELISA, and the entomological inoculation rates (EIR)
      were calculated for both areas. Molecular assessments of pyrethroid knock down
      (kdr) resistance and of insensitive acetylcholinesterase resistance were
      conducted. RESULTS: In Libreville, Anopheles gambiae s.s. S form was the only
      specie of the An. gambiae complex present and was responsible of 9.4 bites per
      person per night. The circumsporozoite index was 0.15% and the entomological
      inoculation rate estimated to be 1.23 infective bites during the four months
      period. In Port-Gentil, Anopheles melas (75.5% of catches) and An. gambiae s.s. S
      form (24.5%) were responsible of 58.7 bites per person per night. The CSP indexes
      were of 1.67% for An. gambiae s.s and 0.28% for An. melas and the EIRs were
      respectively of 1.8 infective bites per week and of 0.8 infective bites per week.
      Both kdr-w and kdr-e mutations in An. gambiae S form were found in Libreville and
      in Port-Gentil. Insensitive acetylcholinesterase has been detected for the first
      time in Gabon in Libreville. CONCLUSION: Malaria transmission exists in both
      town, but with high difference in the level of risk. The co-occurrence of
      molecular resistances to the main families of insecticide has implications for
      the effectiveness of the current vector control programmes that are based on
      pyrethroid-impregnated bed nets.

PMID- 21070656
TI  - KC-SMARTR: An R package for detection of statistically significant aberrations in
      multi-experiment aCGH data.
AB  - BACKGROUND: Most approaches used to find recurrent or differential DNA Copy
      Number Alterations (CNA) in array Comparative Genomic Hybridization (aCGH) data
      from groups of tumour samples depend on the discretization of the aCGH data to
      gain, loss or no-change states. This causes loss of valuable biological
      information in tumour samples, which are frequently heterogeneous. We have
      previously developed an algorithm, KC-SMART, that bases its estimate of the
      magnitude of the CNA at a given genomic location on kernel convolution (Klijn et
      al., 2008). This accounts for the intensity of the probe signal, its local
      genomic environment and the signal distribution across multiple samples. RESULTS:
      Here we extend the approach to allow comparative analyses of two groups of
      samples and introduce the R implementation of these two approaches. The
      comparative module allows for a supervised analysis to be performed, to enable
      the identification of regions that are differentially aberrated between two user
      defined classes.We analyzed data from a series of B- and T-cell lymphomas and
      were able to retrieve all positive control regions (VDJ regions) in addition to a
      number of new regions. A t-test employing segmented data, that we implemented,
      was also able to locate all the positive control regions and a number of new
      regions but these regions were highly fragmented. CONCLUSIONS: KC-SMARTR offers
      recurrent CNA and class specific CNA detection, at different genomic scales, in a
      single package without the need for additional segmentation. It is memory
      efficient and runs on a wide range of machines. Most importantly, it does not
      rely on data discretization and therefore maximally exploits the biological
      information in the aCGH data.The program is freely available from the
      Bioconductor website http://www.bioconductor.org/ under the terms of the GNU
      General Public License.

PMID- 21070657
TI  - Supernumerary, ectopic tooth in the maxillary antrum presenting with recurrent
      haemoptysis.
AB  - BACKGROUND: Ectopic eruption of teeth in non-dental sites is a rare phenomenon
      and can present in a variety of ways such as chronic or recurrent sinusitis,
      sepsis, nasolacrimal duct obstruction, headaches, ostiomeatal complex disease and
      facial numbness. However, presentation of such patients with recurrent
      haemoptysis has not been described in the literature so far. We have described a
      case of an ectopic, supernumerary molar tooth in the maxillary antrum in a
      patient who initially presented with haemoptysis. CASE PRESENTATION: A 45-year
      old male presented with a 2-month history of episodic haemoptysis. A pedunculated
      growth from the inferior nasal turbinate was seen with fibre-optic visualization.
      Although the patient was empirically started on antibiotic and anti-allergic
      therapy, there was no improvement after a few weeks and the patient had recurrent
      episodes of haemoptysis. Fibre-optic visualization was repeated showing bilateral
      osteomeatal erythema. Computed tomography scan of the paranasal sinuses
      demonstrated complete opacification of the left maxillary antrum along with a
      focal area of density comparable to bone. An ectopic, supernumerary molar tooth
      was found in the left maxillary antrum on endoscopic examination and subsequently
      removed. In addition, copious purulent discharge was seen. Post-operatively, the
      patient was treated with a 10-day course of oral amoxicillin-clavulanate. On
      follow-up, he reported resolution of symptoms. CONCLUSION: Recurrent haemoptysis
      has not been described as a presentation for a supernumerary, ectopic tooth in
      literature before. We recommend that in patients with sinusitis-type of
      opacification of maxillary antrum and whose condition is refractory to
      conventional medical treatment, consideration should be given to the
      investigation of possible underlying anomalies as the cause of such symptoms.
      Presence of foreign bodies and ectopic teeth in paranasal sinuses can be reliably
      excluded with the use of appropriate radiological imaging and endoscopic
      examination.

PMID- 21070658
TI  - Rational design of modular circuits for gene transcription: A test of the bottom
      up approach.
AB  - BACKGROUND: Most of synthetic circuits developed so far have been designed by an
      ad hoc approach, using a small number of components (i.e. LacI, TetR) and a trial
      and error strategy. We are at the point where an increasing number of modular,
      inter-changeable and well-characterized components is needed to expand the
      construction of synthetic devices and to allow a rational approach to the design.
      RESULTS: We used interchangeable modular biological parts to create a set of
      novel synthetic devices for controlling gene transcription, and we developed a
      mathematical model of the modular circuits. Model parameters were identified by
      experimental measurements from a subset of modular combinations. The model
      revealed an unexpected feature of the lactose repressor system, i.e. a residual
      binding affinity for the operator site by induced lactose repressor molecules.
      Once this residual affinity was taken into account, the model properly reproduced
      the experimental data from the training set. The parameters identified in the
      training set allowed the prediction of the behavior of networks not included in
      the identification procedure. CONCLUSIONS: This study provides new quantitative
      evidences that the use of independent and well-characterized biological parts and
      mathematical modeling, what is called a bottom-up approach to the construction of
      gene networks, can allow the design of new and different devices re-using the
      same modular parts.

PMID- 21070659
TI  - A framework for assessing the feasibility of malaria elimination.
AB  - The recent scale-up of malaria interventions, the ensuing reductions in the
      malaria burden, and reinvigorated discussions about global eradication have led
      many countries to consider malaria elimination as an alternative to maintaining
      control measures indefinitely. Evidence-based guidance to help countries weigh
      their options is thus urgently needed. A quantitative feasibility assessment that
      balances the epidemiological situation in a region, the strength of the public
      health system, the resource constraints, and the status of malaria control in
      neighboring areas can serve as the basis for robust, long-term strategic
      planning. Such a malaria elimination feasibility assessment was recently prepared
      for the Minister of Health in Zanzibar. Based on the Zanzibar experience, a
      framework is proposed along three axes that assess the technical requirements to
      achieve and maintain elimination, the operational capacity of the malaria
      programme and the public health system to meet those requirements, and the
      feasibility of funding the necessary programmes over time. Key quantitative and
      qualitative metrics related to each component of the assessment are described
      here along with the process of collecting data and interpreting the results.
      Although further field testing, validation, and methodological improvements will
      be required to ensure applicability in different epidemiological settings, the
      result is a flexible, rational methodology for weighing different strategic
      options that can be applied in a variety of contexts to establish data-driven
      strategic plans.

PMID- 21070660
TI  - Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration
      in persistent and transient infections in young women.
AB  - BACKGROUND: HPV burden is a predictor for high-grade cervical intraepithelial
      neoplasia and cancer. The natural history of HPV load in young women being
      recently exposed to HPV is described in this paper. METHODS: A total of 636
      female university students were followed for 2 years. Cervical specimens with HPV
      16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type
      specific and beta-globin real-time PCR assays. Proportional hazards regression
      was used to estimate hazard ratios (HR) of infection clearance. Generalized
      estimating equations assessed whether HPV loads was predictive of HPV infection
      at the subsequent visit. RESULTS: HPV loads were consistently higher among women
      <25 years old, and those who had multiple sex partners, multiple HPV type
      infections and smokers. HPV-16 integration was encountered only in one sample.
      Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8,
      95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI:
      1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and
      infection clearance followed a clear dose-response pattern, after adjusting for
      age and number of sexual partners. GEE Odds Ratios for HPV persistence of the
      middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV
      16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between
      HPV-31 or -45 DNA loads and persistence. CONCLUSIONS: The association between HPV
      load and persistence is not uniform across high-risk genital genotypes. HPV-16
      integration was only rarely demonstrated in young women.

PMID- 21070661
TI  - Toward a bioethical issue: induced multiple pregnancies and neonatal outcomes.
AB  - Assisted reproductive technology has made great progress during the last three
      decades. After the initial enthusiasm, many ethical, legal and social issues
      related to the application of these procedures began to evolve. Multifetal
      pregnancy and fetal reduction, embryo cryopreservation, preimplantation genetic
      diagnosis, risks of birth defects and other adverse outcome associated with
      assisted reproductive technology are issues that have to be addressed building
      future collaborative studies and continuing the debate on related ethical issues.

PMID- 21070662
TI  - Schizophrenia and vitamin D related genes could have been subject to latitude
      driven adaptation.
AB  - BACKGROUND: Many natural phenomena are directly or indirectly related to
      latitude. Living at different latitudes, indeed, has its consequences with being
      exposed to different climates, diets, light/dark cycles, etc. In humans, one of
      the best known examples of genetic traits following a latitudinal gradient is
      skin pigmentation. Nevertheless, also several diseases show latitudinal clinals
      such as hypertension, cancer, dismetabolic conditions, schizophrenia, Parkinson's
      disease and many more. RESULTS: We investigated, for the first time on a wide
      genomic scale, the latitude-driven adaptation phenomena. In particular, we
      selected a set of genes showing signs of latitude-dependent population
      differentiation. The biological characterization of these genes showed enrichment
      for neural-related processes. In light of this, we investigated whether genes
      associated to neuropsychiatric diseases were enriched by Latitude-Related Genes
      (LRGs). We found a strong enrichment of LRGs in the set of genes associated to
      schizophrenia. In an attempt to try to explain this possible link between
      latitude and schizophrenia, we investigated their associations with vitamin D. We
      found in a set of vitamin D related genes a significant enrichment of both LRGs
      and of genes involved in schizophrenia. CONCLUSIONS: Our results suggest a
      latitude-driven adaptation for both schizophrenia and vitamin D related genes. In
      addition we confirm, at a molecular level, the link between schizophrenia and
      vitamin D. Finally, we discuss a model in which schizophrenia is, at least
      partly, a maladaptive by-product of latitude dependent adaptive changes in
      vitamin D metabolism.

PMID- 21070664
TI  - Diagnostic accuracy of plasma NT-proBNP levels for excluding cardiac
      abnormalities in the very elderly.
AB  - BACKGROUND: In the elderly the diagnosis of chronic heart failure is often
      challenging and the availability of echocardiography can be limited. Plasma
      levels of NT-proBNP are valuable tools to diagnose patients with heart failure.
      However, the performance of this biomarker to detect cardiac abnormalities in the
      very elderly remains unclear. The aims of this study were to investigate the
      relation between NT-proBNP and cardiac abnormalities and to evaluate the use of
      NT-proBNP to exclude structural and functional cardiac abnormalities in a
      community-based sample of "well-functioning" nonagenarians. METHODS: A diagnostic
      cross-sectional study embedded within the Leiden 85-plus Study in the
      municipality of Leiden, the Netherlands. Plasma NT-proBNP levels were measured
      and 2-dimensional echocardiography was performed in a subgroup of 80 well
      functioning nonagenarians. Linear regression analysis was used to explore the
      relation between NT-proBNP and cardiac abnormalities and ROC curve analysis was
      used to assess the performance of NT-proBNP to exclude cardiac abnormalities. The
      upper limit of the lowest tertile of NT-proBNP was used as a cut-off value.
      RESULTS: NT-proBNP levels were associated with abnormal left ventricular (LV)
      dimensions, LV systolic and diastolic function, left atrial enlargement and
      valvular heart disease. LV mass, E/A ratio and degree of aortic regurgitation
      were identified as independent predictors of NT-proBNP. NT-proBNP levels were
      higher with greater number of echocardiographic abnormalities (P < 0.001). A cut
      off level of 269.5 pg/mL identified patients with abnormal LV dimensions or
      depressed LV systolic function (sensitivity 85%, negative predictive value (NPV)
      77%, area under the curve 0.75 (95% CI 0.64-0.85)). In addition, high NPV were
      found for LV systolic dysfunction, left atrial enlargement, severe valvular heart
      disease and pulmonary hypertension. The test performance of NT-proBNP to exclude
      any echocardiographic abnormality showed a sensitivity of 82% and a NPV of 65%.
      CONCLUSIONS: In this convenience sample of well-functioning nonagenarians NT
      proBNP was related to a wide variety of functional and structural
      echocardiographic abnormalities. Moreover, NT-proBNP could be used to exclude
      echocardiographic abnormalities in well-functioning nonagenarians and might be
      used to indicate who needs to be referred for further cardiovascular examination.

PMID- 21070663
TI  - Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye
      developmental anomalies.
AB  - BACKGROUND: The size of the vertebrate eye and the retina is likely to be
      controlled at several stages of embryogenesis by mechanisms that affect cell
      cycle length as well as cell survival. A mutation in the zebrafish out of sight
      (out) locus results in a particularly severe reduction of eye size. The goal of
      this study is to characterize the outm233 mutant, and to determine whether
      mutations in the out gene cause microphthalmia in humans. RESULTS: In this study,
      we show that the severe reduction of eye size in the outm233 mutant is caused by
      a mutation in the zebrafish gdf6a gene. Despite the small eye size, the overall
      retinal architecture appears largely intact, and immunohistochemical studies
      confirm that all major cell types are present in outm233 retinae. Subtle cell
      fate and patterning changes are present predominantly in amacrine interneurons.
      Acridine orange and TUNEL staining reveal that the levels of apoptosis are
      abnormally high in outm233 mutant eyes during early neurogenesis. Mutation
      analysis of the GDF6 gene in 200 patients with microphthalmia revealed amino acid
      substitutions in four of them. In two patients additional skeletal defects were
      observed. CONCLUSIONS: This study confirms the essential role of GDF6 in the
      regulation of vertebrate eye size. The reduced eye size in the zebrafish outm233
      mutant is likely to be caused by a transient wave of apoptosis at the onset of
      neurogenesis. Amino acid substitutions in GDF6 were detected in 4 (2%) of 200
      patients with microphthalmia. In two patients different skeletal defects were
      also observed, suggesting pleitrophic effects of GDF6 variants. Parents carrying
      these variants are asymptomatic, suggesting that GDF6 sequence alterations are
      likely to contribute to the phenotype, but are not the sole cause of the disease.
      Variable expressivity and penetrance suggest a complex non-Mendelian inheritance
      pattern where other genetic factors may influence the outcome of the phenotype.

PMID- 21070666
TI  - Rhizobium leguminosarum bv. trifolii rosR is required for interaction with
      clover, biofilm formation and adaptation to the environment.
AB  - BACKGROUND: Rhizobium leguminosarum bv. trifolii is a symbiotic nitrogen-fixing
      bacterium that elicits nodules on roots of host plants Trifolium spp. Bacterial
      surface polysaccharides are crucial for establishment of a successful symbiosis
      with legumes that form indeterminate-type nodules, such as Trifolium, Pisum,
      Vicia, and Medicago spp. and aid the bacterium in withstanding osmotic and other
      environmental stresses. Recently, the R. leguminosarum bv. trifolii RosR
      regulatory protein which controls exopolysaccharide production has been
      identified and characterized. RESULTS: In this work, we extend our earlier
      studies to the characterization of rosR mutants which exhibit pleiotropic
      phenotypes. The mutants produce three times less exopolysaccharide than the wild
      type, and the low-molecular-weight fraction in that polymer is greatly reduced.
      Mutation in rosR also results in quantitative alterations in the polysaccharide
      constituent of lipopolysaccharide. The rosR mutants are more sensitive to surface
      active detergents, antibiotics of the beta-lactam group and some osmolytes,
      indicating changes in the bacterial membranes. In addition, the rosR mutants
      exhibit significant decrease in motility and form a biofilm on plastic surfaces,
      which differs significantly in depth, architecture, and bacterial viability from
      that of the wild type. The most striking effect of rosR mutation is the
      considerably decreased attachment and colonization of root hairs, indicating that
      the mutation affects the first stage of the invasion process. Infection threads
      initiate at a drastically reduced rate and frequently abort before they reach the
      base of root hairs. Although these mutants form nodules on clover, they are
      unable to fix nitrogen and are outcompeted by the wild type in mixed
      inoculations, demonstrating that functional rosR is important for competitive
      nodulation. CONCLUSIONS: This report demonstrates the significant role RosR
      regulatory protein plays in bacterial stress adaptation and in the symbiotic
      relationship between clover and R. leguminosarum bv. trifolii 24.2.

PMID- 21070667
TI  - Expression in E. coli and characterization of the catalytic domain of Botrytis
      cinerea chitin synthase.
AB  - BACKGROUND: Chitin synthase 3a (CHS3a) from Botrytis cinerea (Bc) catalyses the
      multiple transfer of N-acetylglucosamine (GlcNAc) residues to the growing chitin
      chain. Chitin, a beta-1,4 linked GlcNAc homopolymer, is an essential cell wall
      component of filamentous fungi. Chitin synthase, processive membranous protein,
      has been recognized as a promising target for new antifungicides. Enzymatic
      characterizations of chitin synthases have been limited, mainly because purity
      and amounts of integral enzyme obtained after purification procedures have not
      been sufficient. FINDINGS: We undertook the preparation of two BcCHS3a fragment
      proteins, containing only the central domain and devoid of the N-terminal and
      transmembrane C-terminal regions. The central domain of CHS3a, named SGC (Spsa
      GntI Core), is conserved in all UDP-glycosyltransferases and it is believed to
      contain the active site of the enzyme. CHS3a-SGC protein was totally expressed as
      inclusion bodies in Escherichia coli. We performed recombinant CHS3a-SGC
      purification in denaturing conditions, followed by a refolding step. Although
      circular dichroism spectra clearly exhibited secondary structures of renatured
      CHS3a-SGC, no chitin synthase activity was detected. Nevertheless CHS3a-SGC
      proteins show specific binding for the substrate UDP-GlcNAc with a dissociation
      constant similar to the Michaelis constant and a major contribution of the uracil
      moiety for recognition was confirmed. CONCLUSIONS: Milligram-scale quantities of
      CHS3a-SGC protein with native-like properties such as specific substrate UDP
      GlcNAc binding could be easily obtained. These results are encouraging for
      subsequent heterologous expression of full-length CHS3a.

PMID- 21070665
TI  - High diversity of root associated fungi in both alpine and arctic Dryas
      octopetala.
AB  - BACKGROUND: Dryas octopetala is a widespread dwarf shrub in alpine and arctic
      regions that forms ectomycorrhizal (ECM) symbiotic relationships with fungi. In
      this study we investigated the fungal communities associated with roots of D.
      octopetala in alpine sites in Norway and in the High Arctic on Svalbard, where we
      aimed to reveal whether the fungal diversity and species composition varied
      across the Alpine and Arctic regions. The internal transcribed spacer (ITS)
      region of nuclear ribosomal DNA was used to identify the fungal communities from
      bulk root samples obtained from 24 plants. RESULTS: A total of 137 operational
      taxonomic units (OTUs) were detected (using 97% similarity cut off during
      sequence clustering) and well-known ECM genera such as Cenococcum, Cortinarius,
      Hebeloma, Inocybe and Tomentella occurred frequently. There was no decrease in
      fungal diversity with increasing latitude. The overall spatial heterogeneity was
      high, but a weak geographical structuring of the composition of OTUs in the root
      systems was observed. Calculated species accumulation curves did not level off.
      CONCLUSIONS: This study indicates that the diversity of fungi associated with D.
      octopetala does not decrease in high latitude arctic regions, which contrasts
      observations made in a wide spectrum of other organism groups. A high degree of
      patchiness was observed across root systems, but the fungal communities were
      nevertheless weakly spatially structured. Non-asymptotical species accumulation
      curves and the occurrence of a high number of singletons indicated that only a
      small fraction of the fungal diversity was detected.

PMID- 21070668
TI  - Effect of 3D-scaffold formation on differentiation and survival in human neural
      progenitor cells.
AB  - BACKGROUND: 3D-scaffolds have been shown to direct cell growth and
      differentiation in many different cell types, with the formation and
      functionalisation of the 3D-microenviroment being important in determining the
      fate of the embedded cells. Here we used a hydrogel-based scaffold to investigate
      the influences of matrix concentration and functionalisation with laminin on the
      formation of the scaffolds, and the effect of these scaffolds on human neural
      progenitor cells cultured within them. METHODS: In this study we used different
      concentrations of the hydrogel-based matrix PuraMatrix. In some experiments we
      functionalised the matrix with laminin I. The impact of concentration and
      treatment with laminin on the formation of the scaffold was examined with atomic
      force microscopy. Cells from a human fetal neural progenitor cell line were
      cultured in the different matrices, as well as in a 2D culture system, and were
      subsequently analysed with antibody stainings against neuronal markers. In
      parallel, the survival rate of the cells was determined by a live/dead assay.
      RESULTS: Atomic force microscopy measurements demonstrated that the matrices are
      formed by networks of isolated PuraMatrix fibres and aggregates of fibres. An
      increase of the hydrogel concentration led to a decrease in the mesh size of the
      scaffolds and functionalisation with laminin promoted aggregation of the fibres
      (bundle formation), which further reduces the density of isolated fibres. We
      showed that laminin-functionalisation is essential for human neural progenitor
      cells to build up 3D-growth patterns, and that proliferation of the cells is also
      affected by the concentration of matrix. In addition we found that 3D-cultures
      enhanced neuronal differentiation and the survival rate of the cells compared to
      2D-cultures. CONCLUSIONS: Taken together, we have demonstrated a direct influence
      of the 3D-scaffold formation on the survival and neuronal differentiation of
      human neural progenitor cells. These findings emphasize the importance of
      optimizing 3D-scaffolds protocols prior to in vivo engraftment of stem and
      progenitor cells in the context of regenerative medicine.

PMID- 21070669
TI  - Factors associated with Group A Streptococcus emm type diversification in a large
      urban setting in Brazil: a cross-sectional study.
AB  - BACKGROUND: Group A Streptococcus (GAS) strain diversity varies across different
      regions of the world, according to low versus high-income countries. These
      differences may be related to geographic, environmental, socioeconomic, or host
      related factors. However, local factors may also affect strain diversity. We
      compared the emm types of GAS isolates from children with and without sore throat
      in one large urban setting in Brazil. METHODS: Children 3-15 years of age were
      consecutively recruited from slum and non-slum pediatric outpatient clinics
      between April-October, 2008. Throat cultures were performed and data intake forms
      were completed. GAS isolates were typed by emm sequencing. RESULTS: From 2194
      children, 254 (12%) GAS isolates were obtained. Of 238 GAS isolates that were emm
      typed, 61 unique emm types were identified. Simpson's diversity index of the emm
      types was higher among isolates from slum children [97% (96%-98%)] than those of
      non-slum children [92% (89%-96%)]. Two emm types (66.0, 12.0) were more
      frequently isolated from children with sore throat (p < 0.05), and one emm type
      (27G.0) demonstrated a protective effect. CONCLUSIONS: The emm type diversity
      from children attending slum clinics resembled the emm diversity of low income
      countries rather than that of children attending a non-slum clinic in the same
      city. Local factors, such as crowding, may enhance the frequency of GAS
      transmission and horizontal gene transfers that contribute to increased strain
      diversity in the slums. GAS vaccine coverage and control of GAS infections will
      need to take these local factors and strain differences into consideration.

PMID- 21070670
TI  - An unusual complication of polyarteritis nodosa with massive retroperitoneal
      hemorrhage: a case report.
AB  - BACKGROUND AND CASE REPORT: Polyarteritis Nodosa (PAN) is a systemic necrotizing
      vasculitis that affects medium-sized and occasionally involves small arteries
      leading to the disruption of the internal and external elastic lamina and
      contribute to the development of aneurysms. Aneurysms develop at bifurcation of
      major blood vessels; they are prone to thrombosis, rupture and haemorrhage.
      Retroperitoneal haemorrhage around kidneys was previously reported in patients
      with PAN. We report a case of massive retroperitoneal bleeding from inferior
      pancreaticoduodenal artery aneurysm rupture in a 70-year-old female with PAN.
      CONCLUSION: Prognosis of untreated PAN is very poor with 20% 5 year survival
      rate, therefore early recognition of the disease will prevent catastrophic
      complications and improves survival.

PMID- 21070671
TI  - Long-term effect of metformin on blood glucose control in non-obese patients with
      type 2 diabetes mellitus.
AB  - BACKGROUND: We aimed to investigate the long-term effect of metformin on the
      blood glucose control in non-obese patients with type 2 diabetes mellitus.
      METHODS: A retrospective study was performed in 213 patients with type 2 diabetes
      mellitus under the administration of metformin for more than one year. The
      clinical parameters were investigated for 3 years. The obese and non-obese
      individuals were defined as a body mass index (BMI) of 25 kg/m2 or over (n = 105)
      and a BMI of less than 25 kg/m2 (n = 108), respectively. RESULTS: HbA1c levels
      were significantly decreased compared with those at the baseline time. The course
      of HbA1c was similar between the non-obese and the obese groups, while the dose
      of metformin required to control blood glucose was significantly lower in the non
      obese group than in the obese group. The reductions in HbA1c were 1.2% and 1.1%
      at 12 months, 0.9% and 0.9% at 24 months, and 0.8% and 1.0% at 36 months in the
      non-obese and obese groups, respectively. BMI did not change during the
      observation periods. Approximately half of all patients required no additional
      antidiabetic agents or a reduction in other treatments after the initiation of
      metformin in either of the two groups. CONCLUSIONS: The present study
      demonstrated the long-term beneficial effect of metformin in non-obese (BMI < 25
      kg/m2) diabetic patients. This effect appears to be maintained even after the
      observation period of this study, because metformin was limited to a relatively
      low dose in the non-obese group and the observed worsening in glycemic control
      over time can probably be attenuated by increasing the dose of metformin.

PMID- 21070672
TI  - Associations among systemic blood pressure, microalbuminuria and albuminuria in
      dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism.
AB  - BACKGROUND: Hypertension and proteinuria are medical complications associated
      with the multisystemic effects of long-term hypercortisolism in dogs with
      hyperadrenocorticism (HAC). METHODS: This study investigated the relationships
      among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood
      pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs
      affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal
      dependent hyperadrenocorticism (ADH; n = 30). RESULTS: Mean systemic blood
      pressure was similar between clinically healthy dogs and dogs with HAC (p =
      0.803). However the incidence of hypertension was highest in dogs with ADH (p =
      0.017), followed by dogs with PDH, with the lowest levels in clinically healthy
      dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically
      healthy dogs and dogs affected with HAC was significantly different (p < 0.001);
      incidences of albuminuria followed the same pattern of hypertension; highest
      incidence in dogs with ADH, and lowest level in clinically healthy dogs; but
      microalbuminuria showed a different pattern: clinically healthy dogs had highest
      incidences and dogs with ADH had lowest incidence. The presence of albuminuria
      was not associated with blood pressure values, regardless of whether dogs were
      clinically healthy or affected with ADH or PDH (p = 0.306). CONCLUSIONS: Higher
      incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs
      affected with HAC compared to clinically healthy dogs; incidence of hypertension
      and albuminuria was significantly higher in dogs affected with ADH compared to
      PDH. However, presence of albuminuria was not correlated with systemic blood
      pressure.

PMID- 21070673
TI  - Effects of heliox as carrier gas on ventilation and oxygenation in an animal
      model of piston-type HFOV: a crossover experimental study.
AB  - OBJECTIVE: This study aimed to compare gas exchange with heliox and oxygen
      enriched air during piston-type high-frequency oscillatory ventilation (HFOV). We
      hypothesized that helium gas would improve both carbon dioxide elimination and
      arterial oxygenation during piston-type HFOV. METHOD: Five rabbits were prepared
      and ventilated by piston-type HFOV with carrier 50% helium/oxygen (heliox50) or
      50% oxygen/nitrogen (nitrogen50) gas mixture in a crossover study. Changing the
      gas mixture from nitrogen50 to heliox50 and back was performed five times per
      animal with constant ventilation parameters. Arterial blood gas, vital function
      and respiratory test indices were recorded. RESULTS: Compared with nitrogen50,
      heliox50 did not change PaCO2 when stroke volume remained constant, but
      significantly reduced PaCO2 after alignment of amplitude pressure. No significant
      changes in PaO2 were seen despite significant decreases in mean airway pressure
      with heliox50 compared with nitrogen50. CONCLUSION: This study demonstrated that
      heliox enhances CO2 elimination and maintains oxygenation at the same amplitude
      but with lower airway pressure compared to air/O2 mix gas during piston-type
      HFOV.

PMID- 21070674
TI  - PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV
      viral load in chronic hepatitis C patients.
AB  - BACKGROUND: Tight correlation between host circulating CD8+ T cell-mediated
      immune response and control of viral replication is classical characteristic of
      long-term HCV infection. CD8+ T cell maturation/activation markers are expected
      to be associated with viral replication and disease progression in chronic HCV
      infection. The aim of the present study was to explore novel markers on CD8+ T
      cells with ability to evaluate HCV viral replication and disease progression.
      METHODS: PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy
      controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1,
      CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between
      expression of surface markers and HCV viral load or ALT was studied. RESULTS:
      Declined naive and increased TEMRA CD8+ T subsets were found in HCV-infected
      individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and
      HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than
      healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite
      trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+
      TEM (p < 0.0001) and TEMRA (p = 0.0015) was positively correlated with HCV viral
      load while HLA-DR expression on non-naive CD8+ T cell subsets (p < 0.05) was
      negatively correlated with HCV viral load. CONCLUSION: PD-1 level on peripheral
      CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected
      patients, which made PD-1 a novel indicator to evaluate HCV replication and
      disease progression in chronic hepatitis C patients.

PMID- 21070675
TI  - Responsiveness and minimal important differences after revision total hip
      arthroplasty.
AB  - BACKGROUND: The health-related quality of life (HRQoL) is currently weighted more
      heavily when evaluating health status, particularly regarding medical treatments
      and interventions. However, it is rarely used by physicians to compare
      responsiveness. Additionally, responsiveness estimates derived by the Harris Hip
      Score (HHS) and the Short Form 36 (SF-36) before and after revision total hip
      arthroplasty (THA) have not been clinically compared. This study compared
      responsiveness and minimal important differences (MID) between HHS and SF-36.
      METHODS: All revision THA patients completed the disease-specific HHS and the
      generic SF-36 before and 6 months after surgery. Scores using these instruments
      were interpreted by generalized estimating equation (GEE) before and after
      revision THA. The bootstrap estimation and modified Jacknife test were used to
      derive 95% confidence intervals for differences in the responsiveness estimates.
      RESULTS: Comparisons of effect size (ES), standardized response means (SRM),
      relative efficiency (RE) (>1) and MID indicated that the responsiveness of HHS
      was superior to that of SF-36. The ES and SRM for pain and physical functions in
      the HHS were significantly larger than those of the SF-36 (p < 0.001).
      CONCLUSION: The data in this study indicated that clinicians and health
      researchers should weight disease-specific measures more heavily than generic
      measures when evaluating treatment outcomes.

PMID- 21070677
TI  - Female heterozygotes for the hypomorphic R40H mutation can have ornithine
      transcarbamylase deficiency and present in early adolescence: a case report and
      review of the literature.
AB  - INTRODUCTION: Ornithine transcarbamylase deficiency is the most common hereditary
      urea cycle defect. It is inherited in an X-linked manner and classically presents
      in neonates with encephalopathy and hyperammonemia in males. Females and males
      with hypomorphic mutations present later, sometimes in adulthood, with episodes
      that are frequently fatal. CASE PRESENTATION: A 13-year-old Caucasian girl
      presented with progressive encephalopathy, hyperammonemic coma and lactic
      acidosis. She had a history of intermittent regular episodes of nausea and
      vomiting from seven years of age, previously diagnosed as abdominal migraines. At
      presentation she was hyperammonemic (ammonia 477 MUmol/L) with no other
      biochemical indicators of hepatic dysfunction or damage and had grossly elevated
      urinary orotate (orotate/creatinine ratio 1.866 MUmol/mmol creatinine, reference
      range <500 MUmol/mmol creatinine) highly suggestive of ornithine transcarbamylase
      deficiency. She was treated with intravenous sodium benzoate and arginine and
      made a rapid full recovery. She was discharged on a protein-restricted diet. She
      has not required ongoing treatment with arginine, and baseline ammonia and serum
      amino acid concentrations are within normal ranges. She has had one further
      episode of hyperammonemia associated with intercurrent infection after one year
      of follow up. An R40H (c.119G>A) mutation was identified in the ornithine
      transcarbamylase gene (OTC) in our patient confirming the first symptomatic
      female shown heterozygous for the R40H mutation. A review of the literature and
      correspondence with authors of patients with the R40H mutation identified one
      other symptomatic female patient who died of hyperammonemic coma in her late
      teens. CONCLUSIONS: This report expands the clinical spectrum of presentation of
      ornithine transcarbamylase deficiency to female heterozygotes for the hypomorphic
      R40H OTC mutation. Although this mutation is usually associated with a mild
      phenotype, females with this mutation can present with acute decompensation,
      which can be fatal. Ornithine transcarbamylase deficiency should be considered in
      the differential diagnosis of unexplained acute confusion, even without a
      suggestive family history.

PMID- 21070676
TI  - Production of gamma-aminobutyric acid by Lactobacillus brevis NCL912 using fed
      batch fermentation.
AB  - BACKGROUND: Gamma-aminobutyric acid is a major inhibitory neurotransmitter in
      mammalian brains, and has several well-known physiological functions. Lactic acid
      bacteria possess special physiological activities and are generally regarded as
      safe. Therefore, using lactic acid bacteria as cell factories for gamma
      aminobutyric acid production is a fascinating project and opens up a vast range
      of prospects for making use of GABA and LAB. We previously screened a high GABA
      producer Lactobacillus brevis NCL912 and optimized its fermentation medium
      composition. The results indicated that the strain showed potential in large
      scale fermentation for the production of gamma-aminobutyric acid. To increase the
      yielding of GABA, further study on the fermentation process is needed before the
      industrial application in the future. In this article we investigated the impacts
      of pyridoxal-5'-phosphate, pH, temperature and initial glutamate concentration on
      gamma-aminobutyric acid production by Lactobacillus brevis NCL912 in flask
      cultures. According to the data obtained in the above, a simple and effective fed
      batch fermentation method was developed to highly efficiently convert glutamate
      to gamma-aminobutyric acid. RESULTS: Pyridoxal-5'-phosphate did not affect the
      cell growth and gamma-aminobutyric acid production of Lb. brevis NCL912.
      Temperature, pH and initial glutamate concentration had significant effects on
      the cell growth and gamma-aminobutyric acid production of Lb. brevis NCL912. The
      optimal temperature, pH and initial glutamate concentration were 30-35  degrees
      C, 5.0 and 250-500 mM. In the following fed-batch fermentations, temperature, pH
      and initial glutamate concentration were fixed as 32  degrees C, 5.0 and 400 mM.
      280.70 g (1.5 mol) and 224.56 g (1.2 mol) glutamate were supplemented into the
      bioreactor at 12 h and 24 h, respectively. Under the selected fermentation
      conditions, gamma-aminobutyric acid was rapidly produced at the first 36 h and
      almost not produced after then. The gamma-aminobutyric acid concentration reached
      1005.81 +/- 47.88 mM, and the residual glucose and glutamate were 15.28 +/- 0.51
      g L-1 and 134.45 +/- 24.22 mM at 48 h. CONCLUSIONS: A simple and effective fed
      batch fermentation method was developed for Lb. brevis NCL912 to produce gamma
      aminobutyric acid. The results reveal that Lb. brevis NCL912 exhibits a great
      application potential in large-scale fermentation for the production of gamma
      aminobutyric acid.

PMID- 21070678
TI  - Influence of two breakfast meals differing in glycemic load on satiety, hunger,
      and energy intake in preschool children.
AB  - BACKGROUND: Glycemic load (GL) is the product of glycemic index of a food and
      amount of available carbohydrate in that food divided by 100. GL represents
      quality and quantity of dietary carbohydrate. Little is known about the role of
      GL in hunger, satiety, and food intake in preschool children. The aim of this
      study was to investigate the effect of two breakfast meals differing in GL on
      hunger, satiety, and subsequent food intake at lunch in preschool children aged 4
      6 y. METHODS: Twenty three subjects consumed low-GL (LGL) and high-GL (HGL)
      breakfast meals according to a randomized crossover design followed by an ad
      libitum lunch 4 h after consumption of breakfast. Children were asked to consume
      meals until they are full. Each treatment was repeated twice in non-consecutive
      days and data were averaged. RESULTS: Children in LGL group consumed
      significantly lower amounts of GL, total carbohydrate, energy, energy density,
      and dietary fiber and higher amounts of protein and fat at the breakfast compared
      to those in HGL group. Prior to lunch, children were hungrier in the HGL
      intervention group compared to the LGL intervention group (P < 0.03). However, no
      significant difference was observed between LGL and HGL intervention groups in
      the amount of food and energy consumed during lunch. CONCLUSIONS: Decreased
      hunger in children prior to lunch in LGL group is likely due to higher protein
      and fat content of LGL breakfast. Diets that are low in GL can be recommended as
      part of healthy diet for preschool children.

PMID- 21070679
TI  - Comparison of health related quality of life of primary school deaf children with
      and without motor impairment.
AB  - OBJECTIVE: To compare the health-related quality of life (HRQOL) of primary
      school-age deaf children with or without motor impairment to that of typically
      developing peers. METHODS: This study was a prospective, cross sectional study.
      With age-matched controls, 100 children were analyzed in each of the following
      three categories: normal hearing, hearing impaired without motor impairment, and
      hearing impairment with motor impairment. The Paediatric Quality of Life
      Inventory (PedsQLTM) version 4.0 was used to assess the HRQOL. RESULTS: Hearing
      impairment along with motor impairment in children is associated with
      significantly increased proportions of suboptimal levels of function and
      significantly lower HRQOL. Children with hearing impairment and no motor
      impairment had significantly lower scores in the emotional health and school
      function domains of the PedsQL than children with normal hearing, but there was
      no significant difference in the physical and social health domain scores.
      Children with hearing impairment and motor impairment showed significantly lower
      scores in all domains of the PedsQL compared to children with normal hearing.
      Scores in all four domains of the PedsQL differed between children with hearing
      impairment and no motor impairment and children with hearing impairment and motor
      impairment. CONCLUSION: These findings indicate that children with hearing
      impairment, both with and without motor impairment, have a diminished health
      related quality of life.

PMID- 21070680
TI  - A descriptive social and health profile of a community sample of adults and
      adolescents with Asperger syndrome.
AB  - BACKGROUND: Little is known about the health and social profile of adolescents
      and adults with Asperger syndrome (AS) living in the community. We conducted a
      study to describe the living, employment and psycho-social situation of a
      community sample of forty two adults and adolescents with AS, and to describe
      these indivdiuals' experiences of accessing health services and taking
      medication. FINDINGS: Most respondents (including those over eighteen years of
      age) lived at home with their parents. Most had trouble reading and responding to
      other people's feelings, and coping with unexpected changes. Difficulties with
      life skills, such as cleaning, washing and hygiene were prevalent. The majority
      of respondents were socially isolated and a large minority had been sexually or
      financially exploited. Almost all respondents had been bullied. Mental health
      problems such as anxiety or depression were common. 30% of respondents said that
      they regularly became violent and hit other people and 15% had attempted suicide.
      More positively, the majority of respondents felt that they could access health
      services if they had a health problem. CONCLUSIONS: The results of this study
      suggest a relatively poor social and health profile for many people with Asperger
      syndrome living in the community, with high levels of social problems and social
      exclusion, and difficulties managing day to day tasks such as washing and
      cleaning; these findings support the results of other studies that have examined
      psycho-social functioning in this group.

PMID- 21070681
TI  - Evaluating housing quality, health and safety using an Internet-based data
      collection and response system: a cross-sectional study.
AB  - BACKGROUND: Typically housing and health surveys are not integrated together and
      therefore are not representative of population health or national housing stocks.
      In addition, the existing channels for distributing information about housing and
      health issues to the general public are limited. The aim of this study was to
      develop a data collection and response system that would allow us to assess the
      Finnish housing stock from the points of view of quality, health and safety, and
      also to provide a tool to distribute information about important housing health
      and safety issues. METHODS: The data collection and response system was tested
      with a sample of 3000 adults (one per household), who were randomly selected from
      the Finnish Population Register Centre. Spatial information about the exact
      location of the residences (i.e. coordinates) was included in the database
      inquiry. People could participate either by completing and returning a paper
      questionnaire or by completing the same questionnaire via the Internet. The
      respondents did not receive any compensation for their time in completing the
      questionnaire. RESULTS: This article describes the data collection and response
      system and presents the main results of the population-based testing of the
      system. A total of 1312 people (response rate 44%) answered the questionnaire,
      though only 80 answered via the Internet. A third of the respondents had
      indicated they wanted feedback. Albeit a majority (>90%) of the respondents
      reported being satisfied or quite satisfied with their residence, there were a
      number of prevalent housing issues identified that can be related to health and
      safety. CONCLUSIONS: The collected database can be used to evaluate the quality
      of the housing stock in terms of occupant health and safety, and to model its
      association with occupant health and well-being. However, it must be noted that
      all the health outcomes gathered in this study are self-reported. A follow-up
      study is needed to evaluate whether the occupants acted on the feedback they
      received. Relying solely on an Internet-based questionnaire for collecting data
      would not appear to provide an adequate response rate for random population-based
      surveys at this point in time.

PMID- 21070682
TI  - Differential expression of interferon-induced microRNAs in patients with chronic
      hepatitis C virus infection treated with pegylated interferon alpha.
AB  - There have been reports of in-vitro interferon (IFN)-mediated antiviral activity
      against the hepatitis C virus (HCV) through microRNAs (miRNAs). The main aim of
      this study was to evaluate the expression of several miRNAs (miR-1, miR-30, miR
      128, miR-196, miR-296) in peripheral blood mononuclear cells (PBMCs) from healthy
      individuals after in vitro IFN-treatment and in PBMCs from patients with chronic
      hepatitis C (CHC) before and 12 hours after the first injection of pegylated IFN
      alpha. We demonstrated that expression of these miRNAs could be recorded in PBMCs
      collected from healthy individuals before and after in-vitro IFN alpha treatment.
      Our analysis revealed that the levels of expression of all miRNAs investigated in
      patients with CHC were different to those in healthy individuals. When levels of
      the miRNAs were measured 12 hours after the first IFN injection, increases in
      expression levels of IFN-induced miRNAs were observed in 25-50% of patients,
      depending on the type of miRNA examined. No correlations were observed between
      HCV viral load, alanine aminotransferase status and expression of miRNA. Together
      these findings suggest that: (i) IFN alpha in-vitro treatment of PBMCs leads to a
      transcriptional induction of all miRNAs investigated; (ii) miRNAs can be induced
      differentially by IFN treatment in patients with HCV. Given the importance of
      miRNAs in defending the host against virus infections, it is possible that IFN
      induced miRNAs may represent an important determinant of the clinical outcome of
      IFN therapy in HCV infection.

PMID- 21070683
TI  - Wing pathology of white-nose syndrome in bats suggests life-threatening
      disruption of physiology.
AB  - White-nose syndrome (WNS) is causing unprecedented declines in several species of
      North American bats. The characteristic lesions of WNS are caused by the fungus
      Geomyces destructans, which erodes and replaces the living skin of bats while
      they hibernate. It is unknown how this infection kills the bats. We review here
      the unique physiological importance of wings to hibernating bats in relation to
      the damage caused by G. destructans and propose that mortality is caused by
      catastrophic disruption of wing-dependent physiological functions. Mechanisms of
      disease associated with G. destructans seem specific to hibernating bats and are
      most analogous to disease caused by chytrid fungus in amphibians.

PMID- 21070684
TI  - A climate for contemporary evolution.
AB  - A new study of divergence in freshwater fish provides strong evidence of rapid,
      temperature-mediated adaptation. This study is particularly important in the
      ongoing debate over the extent and significance of evolutionary response to
      climate change because divergence has occurred in relatively few generations in
      spite of ongoing gene flow and in the aftermath of a significant genetic
      bottleneck, factors that have previously been considered obstacles to evolution.
      Climate change may thus be more likely to foster contemporary evolutionary
      responses than has been anticipated, and I argue here for the importance of
      investigating their possible occurrence.

PMID- 21070686
TI  - Geographical distribution of cercarial dermatitis in Norway.
AB  - Bird schistosomes can cause a disease called cercarial dermatitis, or swimmer's
      itch, in humans. The disease occurs when people have direct contact with fresh
      water or sea water containing the free-swimming cercariae of the flukes. The
      symptoms are well known, and include intense itching, maculae, papulae,
      urticariae and, in some cases, local oedema with enlarged lymph nodes and fever.
      In this study, we present the geographical distribution of freshwater cercarial
      dermatitis in Norway. The study is based on random reports obtained from both
      individuals and physicians treating patients with itching skin rash after
      freshwater bathing. The first case of cercarial dermatitis in Norway was reported
      in 1980 and was traced to a lake near Trondheim in the central part of Norway. In
      the following years, an increasing number of cases were reported, especially in
      southern Norway. However, case reports are distributed almost all over the
      country, even from lakes in northern Norway. As far as we know, these are the
      northernmost case reports in Europe. So far, only one fluke species
      (Trichobilharzia franki) from a single infected snail (Radix auricularia) has
      been identified in Norway. However, unidentified schistosomatid ocellate
      cercariae have been found on several occasions in snails collected from six lakes
      where swimmer's itch is frequently reported. Future studies should be performed
      to identify the fluke species, as well as the most important snail and bird
      hosts, in Norwegian lakes.

PMID- 21070685
TI  - Trends in meat consumption in the USA.
AB  - OBJECTIVE: To characterize the trends, distribution, potential determinants and
      public health implications of meat consumption within the USA. DESIGN: We
      examined temporal trends in meat consumption using food availability data from
      the FAO and US Department of Agriculture (USDA), and further evaluated the meat
      intake by type (red, white, processed) in the National Health and Nutrition
      Examination Surveys (NHANES) linked to the MyPyramid Equivalents Database (MPED).
      RESULTS: Overall meat consumption has continued to rise in the USA and the rest
      of the developed world. Despite a shift towards higher poultry consumption, red
      meat still represents the largest proportion of meat consumed in the USA (58 %).
      Twenty-two per cent of the meat consumed in the USA is processed. According to
      the NHANES 2003-2004, total meat intake averaged 128 g/d. The type and quantities
      of meat reported varied by education, race, age and gender. CONCLUSIONS: Given
      the plausible epidemiological evidence for red and processed meat intake in
      cancer and chronic disease risk, understanding the trends and determinants of
      meat consumption in the USA, where meat is consumed at more than three times the
      global average, should be particularly pertinent to researchers and other public
      health professionals aiming to reduce the global burden of chronic disease.

PMID- 21070687
TI  - Latitudinal gradient in the taxonomic composition of parasite communities.
AB  - Although latitudinal gradients in diversity have been well studied, latitudinal
      variation in the taxonomic composition of communities has received less
      attention. Here, we use a large dataset including 950 surveys of helminth
      endoparasite communities in 650 species of vertebrate hosts to test for
      latitudinal changes in the relative contributions of trematodes, cestodes,
      nematodes and acanthocephalans to parasite assemblages. Although the species
      richness of helminth communities showed no consistent latitudinal variation,
      their taxonomic composition varied as a function of both host type and latitude.
      First, trematodes and acanthocephalans accounted for a higher proportion of
      species in helminth communities of fish, whereas nematodes achieved a higher
      proportion of the species in communities of bird and especially mammal hosts.
      Second, the proportion of trematodes in helminth communities of birds and mammals
      increased toward higher latitudes. Finally, the proportion of nematodes per
      community increased toward lower latitudes regardless of the type of host. We
      present tentative explanations for these patterns, and argue that new insights in
      parasite community ecology can be gained by searching for latitudinal gradients
      not only in parasite species richness, but also in the taxonomic composition of
      parasite assemblages.

PMID- 21070688
TI  - Bipolar cell pathways for color vision in non-primate dichromats.
AB  - Color vision in mammals is based on the expression of at least two cone opsins
      that are sensitive to different wavelengths of light. Furthermore, retinal
      pathways conveying color-opponent signals are required for color discrimination.
      Most of the primates are trichromats, and "color-coded channels" of their retinas
      are unveiled to a large extent. In contrast, knowledge of cone-selective pathways
      in nonprimate dichromats is only slowly emerging, although retinas of dichromats
      like mice or rats are extensively studied as model systems for retinal
      information processing. Here, we review recent progress of research on color
      coded pathways in nonprimate dichromats to identify differences or similarities
      between di- and trichromatic mammals. In addition, we applied immunohistochemical
      methods and confocal microscopy to retinas of different species and present data
      on their neuronal properties, which are expected to contribute to color vision.
      Basic neuronal features such as the "blue cone bipolar cell" exist in every
      species investigated so far. Moreover, there is increasing evidence for chromatic
      OFF channels in dichromats and retinal ganglion cells that relay color-opponent
      signals to the brain. In conclusion, di- and trichromats share similar retinal
      pathways for color transmission and processing.

PMID- 21070689
TI  - The hybrid procedure for the borderline left ventricle.
AB  - IntroductionIn patients with varying degrees of left heart hypoplasia, it is
      often difficult to determine whether the left heart structures are adequate in
      size to support biventricular circulation. Historically, the decision to pursue a
      single ventricle or biventricular repair needed to be made early and was often
      irreversible. The hybrid procedure may be a better initial approach for patients
      with borderline left ventricles. METHODS: We describe a series of four patients
      with various congenital cardiac malformations, all of whom had borderline left
      ventricles. Based on pre-operative echocardiograms, several scoring systems and
      left ventricle volumes were used to predict the optimal type of repair. A left
      ventricular volume of 20 millilitres per square metre was used as the minimum cut
      off value for adequacy of biventricular repair. RESULTS: The left ventricular
      volumes for the patients were 17.1, 23.7, 25.4, and 25.8 millilitres per square
      metre. In none of the four patients were the calculations unanimous in the
      recommendation to pursue either type of repair. All patients underwent the hybrid
      procedure and then eventual single ventricle palliation (two patients) or
      biventricular repair (two patients). All survived with a mean follow-up of 18
      plus or minus 3.9 months. CONCLUSIONS: The hybrid procedure may be the best
      option in patients with a borderline left ventricle. It can serve as a bridge to
      a more definitive repair when patients are older, larger, and for whom the
      decision between single ventricle and biventricular repair can be more easily
      made.

PMID- 21070690
TI  - Acute coronary syndrome in adult patients with coronary artery lesions caused by
      Kawasaki disease: review of case reports.
AB  - Information about acute coronary syndrome caused by Kawasaki disease-related
      coronary artery lesions in adults is sketchy. We reviewed the clinical features
      of 50 adult patients who had an acute coronary syndrome caused by coronary artery
      lesions due to Kawasaki disease or probable Kawasaki disease from 1980 to 2008.
      Of the 50 patients, 43 (90%) were male and seven were female (10%). Their ages at
      the onset of acute coronary syndrome ranged from 18 to 69 years, with a median of
      28 years. The culprit lesion in 43 patients was thrombotic occlusion of an
      aneurysm, and 40 patients had giant aneurysms. In the three patients in whom no
      aneurysms were seen in coronary angiograms performed at the time of acute
      myocardial infarction, either giant aneurysms or aneurysms had been visualised in
      childhood. The initial treatment of acute coronary syndrome was as follows:
      intracoronary thrombolysis, 11; primary percutaneous coronary intervention, 9;
      emergency coronary artery bypass grafting, 3; and medication, 26. Elective
      coronary artery bypass grafting was performed in 15 patients. Three patients (6%)
      died. Of the 27 patients with additional coronary risk factors, 20 were smokers.
      Giant aneurysms due to Kawasaki disease continued to cause acute coronary
      syndrome in adult life with onset at a younger age than typifies that due to
      atherosclerosis in the general population, especially in male population rather
      than female population. Even when giant aneurysms regressed after the acute
      phase, a few patients still developed acute coronary syndrome in adult life.
      Smoking appears to be the most prominent additional risk factor.

PMID- 21070691
TI  - Weight change in infants with a functionally univentricular heart: from surgical
      intervention to hospital discharge.
AB  - OBJECTIVE: The purpose of this study was to assess the pattern of weight change
      from surgical intervention to home discharge and to determine predictors of poor
      growth in this population of infants with congenital cardiac disease. METHODS:
      Neonates with functionally univentricular physiology enrolled in a prospective
      cohort study examining growth between March, 2003 and May, 2007 were included.
      Weights were collected at birth, before surgical intervention, and at hospital
      discharge. In addition, retrospective echocardiographic data and data about post
      operative complications were reviewed. Primary outcome variables were weight-for
      age z-score at discharge and change in weight-for-age z-score between surgery and
      discharge. RESULTS: A total of 61 infants met the inclusion criteria. The mean
      change in weight-for-age z-score between surgery and hospital discharge was minus
      1.5 plus or minus 0.8. Bivariate analysis revealed a significant difference in
      weight-for-age z-score between infants who were discharged on oral feeds, minus
      1.1 plus or minus 0.8 compared to infants with feeding device support minus 1.7
      plus or minus 0.7, p-value equal to 0.01. Lower weight-for-age z-score at birth,
      presence of moderate or greater atrioventricular valve regurgitation, post
      operative ventilation time, and placement of an additional central venous line
      were associated with 60% of the variance in weight-for-age z-score change.
      CONCLUSION: Neonates undergoing staged surgical repair for univentricular
      physiology are at significant risk for growth failure between surgery and
      hospital discharge. Haemodynamically significant atrioventricular valve
      regurgitation and a complex post-operative course were risk factors for poor post
      operative weight gain. Feeding device support appears to be insufficient to
      ensure adequate weight gain during post-operative hospitalisation.

PMID- 21070692
TI  - QT dispersion in childhood obstructive sleep apnoea syndrome.
AB  - The difference between maximal and minimal QT interval and corrected QT interval
      defined as QT dispersion and corrected QT dispersion may represent arrhythmogenic
      risks. This study sought to evaluate QT dispersion and corrected QT dispersion in
      childhood obstructive sleep apnoea syndrome. Forty-four children (34 male) with
      obstructive sleep apnoea syndrome, aged 6.2 plus or minus 3.5 years along with 38
      healthy children (25 male), 6.6 plus or minus 2.1 years underwent
      electrocardiography to measure QT and RR intervals. Means QT dispersion and
      corrected QT dispersion were significantly higher in obstructive sleep apnoea
      syndrome than controls, 52 plus or minus 27 compared to 40 plus or minus 14
      milliseconds (p equal to 0.014), and 71 plus or minus 29 compared to 57 plus or
      minus 19 milliseconds (p equal to 0.010), respectively. Interestingly, QT
      dispersion and corrected QT dispersion in obstructive sleep apnoea syndrome with
      obesity, 57 plus or minus 30 and 73 plus or minus 31 milliseconds, were
      significantly higher than in control, 40 plus or minus 14 and 57 plus or minus 19
      milliseconds (p equal to 0.009 and 0.043, respectively). However, QT dispersion
      and corrected QT dispersion in obstructive sleep apnoea syndrome without obesity,
      43 plus or minus 20 and 68 plus or minus 26 milliseconds, were not significantly
      different. In conclusion, QT dispersion and corrected QT dispersion were
      significantly increased only in childhood obstructive sleep apnoea syndrome with
      obesity. Obesity may be the factor affecting the increased QT dispersion and
      corrected QT dispersion.

PMID- 21070693
TI  - Contemporary management of congenital malformations of the heart in infants with
      Ellis - van Creveld syndrome: a report of nine cases.
AB  - INTRODUCTION: Ellis - van Creveld syndrome is an autosomal recessive disorder
      manifest by short-limb dwarfism, thoracic dystrophy, postaxial polydactyly,
      dysplastic nails and teeth, and an approximately 60% incidence of congenital
      malformations of the heart. Despite patients with Ellis - van Creveld syndrome
      being regarded as having a high surgical risk, few data are available regarding
      their outcomes following surgery for congenital malformations of the heart in the
      current era. MATERIALS AND METHODS: In this retrospective report, we summarise
      the clinical observations and outcomes of nine infants with Ellis - van Creveld
      syndrome who underwent surgery for congenital malformations of the heart between
      2004 and 2009. RESULTS: We identified 15 patients with Ellis - van Creveld
      syndrome during the study period; 11 (73%) had haemodynamically significant
      congenital malformations of the heart warranting surgery. In two of these
      patients, surgery was not performed. Of the nine patients who underwent surgery,
      all of whom were infants, eight (89%) had various forms of an atrioventricular
      septal defect and one patient (11%) had hypoplastic left heart syndrome (mitral
      and aortic atresia). Among the nine patients who underwent surgery, four (44%)
      died at a median of 102 days with a range of 25-149 days post-operatively, mostly
      from respiratory failure. Respiratory morbidity was seen in all surviving
      patients, of whom three underwent tracheostomy. CONCLUSIONS: Surgery for
      congenital malformations of the heart can be successful in infants with Ellis -
      van Creveld syndrome, but mortality is high and post-operative respiratory
      morbidity should be expected.

PMID- 21070695
TI  - New developments on classification and diagnostic systems.

PMID- 21070694
TI  - Diffusion tensor imaging biomarkers for traumatic axonal injury: analysis of
      three analytic methods.
AB  - Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not
      readily identified using conventional neuroimaging modalities. Novel imaging
      modalities such as diffusion tensor imaging (DTI) can detect microstructural
      compromise in white matter (WM) in various clinical populations including TAI.
      DTI-derived data can be analyzed using global methods (i.e., WM histogram or
      voxel-based approaches) or a regional approach (i.e., tractography). While each
      of these methods produce qualitatively comparable results, it is not clear which
      is most useful in clinical research and ultimately in clinical practice. This
      study compared three methods of analyzing DTI-derived data with regard to
      detection of WM injury and their association with clinical outcomes. Thirty
      patients with TAI and 19 demographically similar normal controls were scanned
      using a 3 Tesla magnet. Patients were scanned approximately eight months
      postinjury, and underwent an outcomes assessment at that time. Histogram analysis
      of fractional anisotropy (FA) and mean diffusivity showed global WM integrity
      differences between patients and controls. Voxel-based and tractography analyses
      showed significant decreases in FA within centroaxial structures involved in TAI.
      All three techniques were associated with functional and cognitive outcomes. DTI
      measures of microstructural integrity appear robust, as the three analysis
      techniques studied showed adequate utility for detecting WM injury.

PMID- 21070696
TI  - Paradigm shifts and the development of the diagnostic and statistical manual of
      mental disorders: past experiences and future aspirations.
AB  - OBJECTIVE: Work is currently under way on the Diagnostic and Statistical Manual
      of Mental Disorders (DSM), Fifth Edition, due to be published by the American
      Psychiatric Association in 2013. Dissatisfaction with the current categorical
      descriptive approach has led to aspirations for a paradigm shift for DSM-5.
      METHOD: A historical review of past revisions of the DSM was performed. Efforts
      undertaken before the start of the DSM-5 development process to conduct a state
      of-the science review and set a research agenda were examined to determine if
      results supported a paradigm shift for DSM-5. Proposals to supplement DSM-5
      categorical diagnosis with dimensional assessments are reviewed and critiqued.
      RESULTS: DSM revisions have alternated between paradigm shifts (the first edition
      of the DSM in 1952 and DSM-III in 1980) and incremental improvements (DSM-II in
      1968, DSM-III-R in 1987, and DSM-IV in 1994). The results of the review of the
      DSM-5 research planning initiatives suggest that despite the scientific advances
      that have occurred since the descriptive approach was first introduced in 1980,
      the field lacks a sufficiently deep understanding of mental disorders to justify
      abandoning the descriptive approach in favour of a more etiologically based
      alternative. Proposals to add severity and cross-cutting dimensions throughout
      DSM-5 are neither paradigm shifting, given that simpler versions of such
      dimensions are already a component of DSM-IV, nor likely to be used by busy
      clinicians without evidence that they improve clinical outcomes. CONCLUSIONS:
      Despite initial aspirations that DSM would undergo a paradigm shift with this
      revision, DSM-5 will continue to adopt a descriptive categorical approach, albeit
      with a greatly expanded dimensional component.

PMID- 21070697
TI  - Person-centred integrative diagnosis: conceptual bases and structural model.
AB  - OBJECTIVES: To review the conceptual bases of Person-centred Integrative
      Diagnosis (PID) as a component and contributor to person-centred psychiatry and
      medicine and to outline its design and development. METHOD: An analysis was
      conducted of the historical roots of person-centred psychiatry and medicine,
      tracing them back to ancient Eastern and Western civilizations, to the
      vicissitudes of modern medicine, to recent clinical and conceptual developments,
      and to emerging efforts to reprioritize medicine from disease to patient to
      person in collaboration with the World Medical Association, the World Health
      Organization, the World Organization of Family Doctors, the World Federation for
      Mental Health, and numerous other global health entities, and with the
      coordinating support of the International Network for Person-centered Medicine.
      RESULTS: One of the prominent endeavours within the broad paradigmatic health
      development outlined above is the design of PID. This diagnostic model
      articulates science and humanism to obtain a diagnosis of the person (of the
      totality of the person's health, both ill and positive aspects), by the person
      (with clinicians extending themselves as full human beings), for the person
      (assisting the fulfillment of the person's health aspirations and life project),
      and with the person (in respectful and empowering relationship with the person
      who consults). This broader and deeper notion of diagnosis goes beyond the more
      restricted concepts of nosological and differential diagnoses. The proposed PID
      model is defined by 3 keys: broad informational domains, covering both ill health
      and positive health along 3 levels: health status, experience of health, and
      contributors to health; pluralistic descriptive procedures (categories,
      dimensions and narratives); and evaluative partnerships among clinicians,
      patients, and families. An unfolding research program is focused on the
      construction of a practical guide and its evaluation, followed by efforts to
      facilitate clinical implementation and training. CONCLUSIONS: PID is aimed at
      appraising overall health through pluralistic descriptions and evaluative
      partnerships, and leading through a research program to more effective,
      integrative, and person-centred health care.

PMID- 21070698
TI  - Are there guidelines for the responsible prescription of benzodiazepines?

PMID- 21070699
TI  - Prevalence of pervasive developmental disorders among children at the English
      Montreal School Board.
AB  - OBJECTIVES: The prevalence of pervasive developmental disorders (PDDs) has
      increased. There has been speculation regarding a role of thimerosal-containing
      vaccines (TCVs) in this trend. Our objectives were to determine prevalence rates
      of PDDs among school-aged children, and to evaluate the impact of discontinuation
      of thimerosal use in 1996 in routine childhood vaccines on PDD rates. METHOD:
      Children (n = 23 635) attending kindergarten to Grade 11 were surveyed in 71
      schools from the English Montreal School Board. For children with PDD,
      information was obtained about their diagnostic subtype, age, sex, grade, and
      school. Prevalence rates were calculated for the entire school population and for
      each grade. Prevalence rates were also compared for children born before or after
      1996. RESULTS: Students (n = 187; male to female ratio: 5.4:1) with PDD were
      identified, corresponding to a prevalence of 79.1/10 000 (95% CI 67.8 to 90.4/10
      000). The prevalence was 25.4, 43.6, 9.7, and 0.4 for autistic disorder, PDD not
      otherwise specified, Asperger syndrome, and childhood disintegrative disorder,
      respectively. During the study period, there was a significant linear increase in
      prevalence (OR 1.17 per year; 95% CI 1.12 to 1.23). The trend in prevalence of
      PDDs was unrelated to the discontinuation of TCVs. CONCLUSION: Our study provides
      additional evidence that the PDD rate is close to 1%. We estimate that at least
      11 500 Canadian children aged 2 to 5 years suffer from a PDD. The reasons for the
      upward trend in prevalence could not be determined with our methods.
      Discontinuation of thimerosal use in vaccines did not modify the risk of PDD.

PMID- 21070700
TI  - Dual diagnosis: A national study of psychiatric hospitalization patterns of
      people with developmental disability.
AB  - OBJECTIVE: To report national demographics and diagnostic profiles of people with
      developmental disability hospitalized for psychiatric reasons, and to contrast
      results to psychiatric hospitalizations among patients with no comorbid
      developmental disability. METHOD: People with developmental disability across
      Canada were identified using data administered by the Canadian Institute for
      Health Information. Among this cohort of people with developmental disability,
      records of hospitalization for psychiatric reasons were aggregated for the
      2005/06 fiscal year (April 2005 to March 2006). Descriptive statistics on
      province of residence, age, sex, specific diagnoses, length of stay, and
      hospitalization frequency were calculated and compared with people without
      developmental disability. RESULTS: In Canada, people with developmental
      disability were hospitalized a total of 8378 times in 2005/06; among these, 3478
      (42%) were for psychiatric conditions. The number of people with developmental
      disability hospitalized for a psychiatric condition represents about 2% of the
      general population hospitalized for such conditions. Among people with
      developmental disability hospitalized for a psychiatric condition most were men
      and people aged between 15 and 34 years. For almost all psychiatric disorder
      categories, people with developmental disability were hospitalized at rates
      significantly different than their counterparts without developmental disability.
      Lengths of hospital stays for psychiatric conditions were very similar when
      comparing the study groups; however, people with developmental disability were
      more likely to have 2 or more hospitalizations during the year. CONCLUSIONS:
      People with developmental disability display unique hospitalization patterns,
      compared with the general population.

PMID- 21070701
TI  - Improving reliability of the assessment of the life course of schizophrenia.
AB  - OBJECTIVE: Life course studies of schizophrenia that have used a 3-phase model
      (onset, course, and outcome) have had their use restricted owing to differences
      in definition and methodology. The purpose of this investigation was to describe
      life course data in mathematical terms and to compare the results with the
      findings from other life course studies. METHOD: The study population was
      comprised of 128 of 137 people who were first admitted for schizophrenia to 1 of
      the 2 mental hospitals in Alberta in 1963 and followed until 1997 or death.
      Patient evaluations were based on retrospective and contemporaneous information
      collected from the patients and hospital files, treatment records, and family
      members. Mathematically derived ratings were formulated for course, outcome, and
      onset (pre-admission years). The distribution of the resulting 8 life course
      types was compared with profiles drawn from other such studies reported in the
      literature. RESULTS: The use of mathematical descriptions of onset, course, and
      outcome produced profiles that did not closely match the results of other
      investigations, largely owing to inconsistency across studies. Further, the
      present approach to outcome measurement produced results that were less
      favourable than those found in other studies. CONCLUSIONS: Studies on the life
      course of schizophrenia could be made more comparable by specifying
      mathematically expressed operational definitions of onset, course, and outcome.
      Nonetheless, the use of the term outcome can be questioned as it implies an
      assessment at a specific time rather than providing a summary statement of the
      quality of a life.

PMID- 21070702
TI  - Screening cognitive performance with the Resident Assessment Instrument for
      Mental Health Cognitive Performance Scale.
AB  - OBJECTIVE: The validity of the Cognitive Performance Scale (CPS) embedded in the
      Resident Assessment Instrument-Mental Health (RAI-MH) was evaluated among adult
      psychiatric inpatients. METHODS: The CPS is a brief measure of cognitive
      performance, with scores ranging from 0 (intact) to 6 (very severe impairment).
      The CPS scores were compared with the Mini-Mental State Examination (MMSE) and
      the Montreal Cognitive Assessment (MoCA) scores for 215 adult psychiatric
      inpatients. RESULTS: The CPS scores were significantly correlated with MMSE
      scores (r = -0.69, P < 0.001) and MoCA scores (r = -0.69, P < 0.001). Higher
      scores on the CPS were associated with greater functional impairment, older age,
      and a greater prevalence of dementia diagnoses than lower CPS scores.
      CONCLUSIONS: Pilot data show the CPS is a valid screening measure of cognitive
      performance among adult psychiatric inpatients. Additional research is needed to
      replicate our study using a larger sample with more diverse mental health
      conditions.

PMID- 21070703
TI  - Texas horse dentists feel regulatory bite.

PMID- 21070704
TI  - Rare dental peculiarities associated with the hypomyelinating leukoencephalopathy
      4H syndrome/ADDH.
AB  - PURPOSE: 4H syndrome/ADDH, a disease of the cerebral white matter, seems to be
      associated with delayed tooth eruption and other dental abnormalities, which so
      far could not be assessed conclusively-mainly because patients were too young.
      The aim of this study was to characterize these abnormalities in a sample of
      patients old enough for a reliable assessment. METHODS: Three children, all
      diagnosed with 4H syndrome/ADDH, were followed from approximately 4 to 10 years
      of age and examined clinically and radiographically. In one case, a
      histopathological analysis supplemented these records. RESULTS: All 3 patients
      showed a generalized delay in eruption of the primary and permanent teeth, which
      culminated in complete retention of all primary maxillary central incisors.
      Permanent mandibular second premolars were missing in all children and permanent
      maxillary central incisors of 2 individuals exhibited a concave labial surface,
      while agenesis of the permanent maxillary lateral incisors and natal or neonatal
      teeth were observed in one patient. CONCLUSION: 4H syndrome/ADDH seems to be
      associated with a delay in primary tooth eruption, complete retention of the
      primary maxillary central incisors, and shape abnormalities of the permanent
      maxillary central incisors, which otherwise are very rare. Therefore, a
      neurological examination would appear warranted when these peculiarities are
      encountered.

PMID- 21070706
TI  - Rural Latino farmworker fathers' understanding of children's oral health.
AB  - PURPOSE: This study's purpose was to examine rural Latino fathers' understanding
      of their children's oral health. METHODS: A convenience sample (n=20) of fathers
      from a small agricultural community in California was recruited door-to-door and
      interviewed in their homes. Individual qualitative interviews in Spanish were
      conducted. Interviews were audiotaped, translated, and transcribed. Codes were
      developed, and the text was analyzed for recurrent themes. RESULTS: Fathers came
      from Mexico (n=15) and El Salvador (n=5). Fathers had very little understanding
      of the etiology and clinical signs of dental caries. Overall, 18 of 19 fathers
      reported that their wife was primarily responsible for taking care of the
      children's hygiene. Fathers agreed that children's teeth should be taken care of
      from a young age, considered to be after 2 years. The fathers described very
      minimal hygiene assistance given to children by either parent and often
      considered a verbal reminder to be sufficient assistance. Fathers generally
      thought a child did not need supervision after approximately age 4 (range=1-11
      years). CONCLUSIONS: While rural Latino fathers might not actively participate in
      their children's oral hygiene, they do place value on it. Men are supportive of
      dental treatments, albeit later than recommended. Educational messages aimed at
      these families will disseminate to the fathers, indirectly.

PMID- 21070705
TI  - Comparing gray mineral trioxide aggregate and diluted formocresol in pulpotomized
      human primary molars.
AB  - PURPOSE: The purpose of this multisite, multioperator, prospective, randomized,
      controlled clinical trial was to evaluate the 6-month outcomes of diluted
      formocresol (DFC) compared to gray mineral trioxide aggregate (GMTA) as pulpotomy
      medicament. METHODS: Determined by a power analysis, 252 molars of 152 children
      were recruited. The teeth were randomly assigned to receive GMTA or DFC. At the 6
      month follow-up, 118 children with 203 treated teeth were evaluated. RESULTS:
      Four blinded and calibrated evaluators scored each radiograph for pathologies.
      Clinical success was similar for DFC (97%) and GMTA (100%), (P<.09). Radiographic
      success differed significantly (P<.04) for DFC (86%) and GMTA (95%). Pulp canal
      obliteration was radiographically observed in 25% of the DFC group and in 37% of
      the GMTA group (P=.07). Dentin bridging was observed in 22% of the GMTA group but
      was not found in the DFC group (P<.01). CONCLUSION: Teeth treated with GMTA
      showed more favorable radiographic outcomes than DFC at 6 months post-treatment.

PMID- 21070707
TI  - Double vs single primary teeth extraction approach as prevention of permanent
      maxillary canines ectopic eruption.
AB  - PURPOSE: To compare the effects of extraction of primary maxillary canines and
      first molars (double extraction approach) vs primary maxillary canines extraction
      (single extraction approach) in cases of ectopic permanent maxillary canines
      (PMCs). METHODS: Palatally or centrally displaced PMCs were randomly assigned as
      follows: single extraction (Group 1=29 patients, 52 canines); double extraction
      (Group 2=30 patients, 56 canines). PMCs inclination to the midline and to the
      long axis of the lateral incisor, mesiodistal position of the PMCs crown, and
      first premolars angulation to the midline were measured on panoramic radiographs
      at T0 and after 18 months (T1), on average. Between-group statistical comparison
      was carried out on T0-T1 changes for all the radiographic variables.
      Eruption/noneruption of the PMCs was also assessed. RESULTS: Group 2 exhibited
      improvements in PMCs intrabony position among all the examined variables
      (P<.001), obtaining a greater parallelism between the roots of the PMCs and the
      adjacent lateral incisors (P<.001). An improved position of the first premolars
      due to a reduced angulation (P<.001) was also observed. Clinical success rates
      showed no statistically significant difference. CONCLUSIONS: The double
      extraction approach proved to be a more effective procedure vs the single
      extraction approach in improving permanent maxillary canines' intraosseous
      position.

PMID- 21070708
TI  - Use of anterior veneered stainless steel crowns by pediatric dentists.
AB  - PURPOSE: The purpose of this study was to evaluate the use of anterior veneered
      stainless steel crowns (AVSSCs) by pediatric dentists. METHODS: A questionnaire
      was sent to 2,600 active members of the American Academy of Pediatric Dentistry
      with a follow-up request after 8 weeks. Respondents were asked about the
      utilization of AVSSCs in their practice and during their graduate training
      program. In addition, the participants were asked to rank, in order of
      preference, the type of restorations for treating primary anterior teeth, as well
      as factors that influenced their choice of treatment. RESULTS: Among 849
      respondents, 456 (51%) utilized AVSSCs in their practice; 187 (41%) selected
      AVSSCs as their first choice for the complete coverage for primary anterior
      teeth; and 278 (61%) selected extent of caries as the main factor that influenced
      their restoration choice. The respondents' major concern (73%) was durability of
      AVSSCs. CONCLUSION: The anterior veneered stainless steel crown is a common
      restoration to treat primary anterior teeth among pediatric dentists.

PMID- 21070710
TI  - Solitary median maxillary central incisor syndrome and holoprosencephaly: a case
      report.
AB  - Solitary median maxillary central incisor syndrome (SMMCIS) is a rare anomaly
      that affects 1 in 50,000 live births. Of unknown etiology, SMMCIS is
      characterized by the presence of a single central incisor located on the
      maxillary midline and may be associated with developmental defects and systemic
      alterations. SMMCIS also is associated with short stature, mild forms of
      deviation in craniofacial morphology, and intellectual disability. The purposes
      of this paper were to: describe the clinical case of an 8-year-old boy with a
      permanent central incisor located at the midline in association with
      holoprosencephaly; and highlight the most important aspects related to diagnosis
      and treatment of solitary median maxillary central incisor syndrome.

PMID- 21070709
TI  - Addressing childhood overweight and obesity in the dental office: rationale and
      practical guidelines.
AB  - The prevalence of childhood obesity has increased dramatically in the past 3
      decades. The purposes of this paper were to: review health and dental
      implications; present guidelines for tracking body mass index (BMI) percentiles
      in children; and discuss reasonable "next steps" to take in communicating with
      parents and other health professionals. The health implications of childhood
      obesity warrant early monitoring, diagnosis, and treatment. Trends in visitation
      patterns of children offer dentists an unusual opportunity and an important role
      in addressing childhood obesity through regular monitoring of height, weight, and
      BMI percentiles. Dentists' collaborations with pediatricians, registered
      dietitians, and parents have the potential to address the detrimental physical
      and psychosocial effects of childhood obesity. We encourage dentists to determine
      height, weight, and BMI percentiles for their patients at least annually. They
      should refer patients with unhealthy weight trajectories to pediatricians or
      family physicians and consider ancillary referrals to registered dietitians.

PMID- 21070711
TI  - Multidisciplinary approach of a crown-root fracture using intentional
      replantation: a case report.
AB  - Crown-root fractures are complex traumatic injuries that require
      multidisciplinary management and afford uncertain prognosis. The purpose of this
      clinical article was to report the case of crown-root fracture where a
      multidisciplinary approach was successfully executed. A 10-year-old male patient
      who suffered a complicated crown-root fracture on a permanent maxillary central
      incisor was treated using an intentional 180 degrees -rotation replantation
      technique, followed by endodontic therapy and restoration with resin composite.
      Two years after the initial treatment, the case was stable and the tooth was
      restored with a resin core and a ceramic crown. This article describes how
      adequate multidisciplinary treatment planning, coordination, and execution are
      necessary for similar cases to be properly managed. It can be concluded that the
      intentional replantation with 180 degrees -rotation allowed a more conservative
      approach, showing, in this case, a clinical success without resorption.

PMID- 21070712
TI  - Combined effect of paste containing casein phosphopeptide-amorphous calcium
      phosphate and fluoride on enamel lesions: an in vitro pH-cycling study.
AB  - PURPOSE: The purpose of this study was to show through enamel remineralization
      that a combination of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)
      and fluoride is better than fluoride alone when the processing time for
      remineralization is short. METHODS: The bovine enamel slabs (n=28) were subjected
      to pH cycling for 4 days. Paste containing CPP-ACP and/or fluoride was applied
      for 30 minutes daily. The sections were observed using a polarizing microscope
      and microradiographs. RESULTS: In the groups treated solely with sodium fluoride
      (NaF) solution, tissue loss on the enamel surface was observed. On the other
      hand, in the groups that had been treated with a mixture of the NaF solution and
      CPP-ACP, the enamel surface was maintained. CONCLUSIONS: These results show that
      casein phosphopeptide-amorphous calcium phosphate-containing paste has the
      ability to maintain the enamel surface; the combined use of CPP-ACP paste and
      fluoride enhances this ability, thereby reducing demineralization.

PMID- 21070713
TI  - KBG syndrome: clinical features and specific dental findings.
AB  - PURPOSE: This investigation sought to identify the common manifestations of KBG
      syndrome in the literature and to determine the major oral abnormalities in a 12
      year-old Chinese boy. METHODS: PUBMED search, using the keyword phrase "KBG
      syndrome," produced 20 articles. Due to the disparities in the quality of
      evaluations in the reports, any physical feature that was not discussed was
      assumed to be absent. RESULTS: Of the 54 cases, including the present case, 36
      (67%) were males. Mental retardation or global developmental delay was reported
      in 42 (78%) cases, while 46 (85%) exhibited shortness of stature. Oral features
      occurred in 53 (98%) cases; macrodontia was present in 49 (96%) cases; the
      present case was the only one with hyperdontia and a talon cusp. Other features
      were craniofacial anomalies, followed by abnormalities of the nose, hand, mouth,
      eyes, eyebrows, philtrum, costovertebrae, ears, and, less frequently, low
      hairline and lower extremity abnormalities. CONCLUSIONS: Cardinal features of KBG
      syndrome include facial dysmorphism, short stature, skeletal anomalies, and mild
      developmental delay; intraorally, macrodontia of the maxillary central incisors
      occurs in most cases. This is the first known report of KBG syndrome in a Chinese
      subject and the only case with hyperdontia and a talon cusp.

PMID- 21070714
TI  - Dental manifestations associated with Seckel syndrome type II: a case report.
AB  - Seckel syndrome is a rare form of primordial dwarfism that is characterized by
      short stature, skeletal defects, mental retardation, and characteristic facial
      features such as microcephaly, micrognathia, and a bird-head appearance. Dental
      findings include hypodontia, enamel hypoplasia, crowding, and Class II
      malocclusion. The purpose of this paper was to report the case of a female
      patient with Seckel syndrome type II and describe her orodental manifestations.
      She presented with interesting dental findings, including gingival hyperplasia,
      recession and ulceration, significant crowding, and early exfoliation of the
      primary dentition with accelerated eruption of the permanent dentition. The
      patient received comprehensive dental care under general anesthesia, and hard and
      soft tissue samples were collected for histologic analysis. The patient was
      followed for over 3 years.

PMID- 21070715
TI  - High-flow arteriovenous malformations of the mandible and the maxilla: report of
      2 cases.
AB  - Arteriovenous malformations (AVMs) are rare vascular lesions that can be life
      threatening due to potential massive hemorrhage. AVMs can be subdivided according
      to the type of vessel involved (capillary, venous, and arterial) and can be
      categorized, according to hemodynamic features, into high-flow and low-flow
      lesions. AVM of the jaws is an uncommon disease. Clinical signs and symptoms of
      AVM may include pain, erythematous gingiva, spontaneous gingival bleeding,
      resorption and mobility of teeth, soft tissue discoloration, facial swelling, and
      asymmetry. Radiographically, AVMs are osteolytic and frequently have indistinct
      margins. Computed tomography can demonstrate enhancement of the lesions, while
      angiography can depict distended feeder vessels and arteriovenous shunts.
      Magnetic resonance imaging can visualize flow voids in high-flow abnormalities.
      The purpose of this paper was to present 2 high-flow cases of arteriovenous
      malformations: one with a large AVM lesion in the mandible that presented
      clinically as a discoloration on the mucosa and gingiva with loss of lip
      sensation; and the second with a lesion in the maxilla discovered during an
      extraction of a root fragment. Management of the lesions was achieved by
      embolization.

PMID- 21070716
TI  - New anticoagulants and the future of cardiology.

PMID- 21070717
TI  - Cardiac resynchronisation therapy is cost effective.

PMID- 21070718
TI  - How should we conduct studies on interventions that promote clinically relevant
      increases in physical activity?

PMID- 21070719
TI  - Economic assessment of cardiac resynchronization therapy.
AB  - INTRODUCTION AND OBJECTIVES: Cardiac resynchronization devices have been shown to
      be effective in treating heart failure. They reduce overall mortality, heart
      failure mortality and hospitalizations due to heart failure. The aim of this
      study was to compare the cost-effectiveness of cardiac resynchronization therapy
      (CRT) with that of optimal drug therapy (ODT) by carrying out an economic
      assessment in the Spanish healthcare setting. METHODS: An existing model was
      adapted for use in the Spanish healthcare setting. The effectiveness of cardiac
      resynchronization therapy was determined from published systematic reviews. The
      costs of the various interventions were determined using a range of Spanish data
      sources. The model adopted the perspective of the public health system and the
      time horizon considered was the remainder of the patient's life. The outcome
      variables were life-years gained and quality-adjusted life-years (QALYs) gained.
      RESULTS: Overall, ODT, CRT and CRT with a defibrillator resulted in gains of
      2.11, 2.8 and 3.19 QALYs, respectively, at a cost of ?11,722, ?31,629 and
      ?52,592, respectively. Consequently, each QALY gained with CRT relative to ODT
      involved the consumption of ?28,612 of additional resources. Similarly, the use
      of CRT with a defibrillator cost an additional ?53,547 per QALY relative to CRT
      without a defibrillator. CONCLUSIONS: The use of CRT without a defibrillator
      could be a cost-effective alternative to ODT for treating heart failure in a
      carefully selected group of patients. The study results were sensitive to
      uncertainties in many of the variables used in the model.

PMID- 21070721
TI  - Carotid artery stiffness as an early marker of vascular lesions in children and
      adolescents with cardiovascular risk factors.
AB  - INTRODUCTION AND OBJECTIVES: The availability of a noninvasive marker of vascular
      lesions that enables their detection in the preclinical phase would be of great
      benefit for cardiovascular disease prevention. The aim of this study was to
      investigate the usefulness of a range of indices of arterial wall stiffness in
      the common carotid artery, as derived using high-resolution Doppler
      ultrasonography, for identifying vascular damage in children with risk factors.
      METHODS: The study involved 99 children (age, 8-16 years) divided into two
      groups: 65 had cardiovascular risk factors (45 obesity, 20 dyslipidemia) and 34
      were controls. Family histories of cardiovascular risk factors and anthropometric
      and biochemical measurements were recorded. Functional parameters of arterial
      stiffness (i.e., arterial compliance, elastic modulus, beta stiffness index,
      pulse wave velocity, and augmentation index) and the intima-media thickness were
      also measured. RESULTS: Some functional vascular parameters were higher in obese
      children than controls: there were significant differences in beta stiffness
      index (P< .02), elastic modulus (P< .001) and pulse wave velocity (P< .01). There
      was a significant difference in arterial compliance between dyslipidemics and
      controls (P< .05). No significant difference in intima-media thickness was found
      between the groups. In obese children, there were positive correlations between
      body mass index, systolic pressure and triglyceride levels and vascular
      parameters (i.e., elastic modulus and pulse wave velocity); in dyslipidemic
      children, triglyceride levels and the same parameters were correlated.
      CONCLUSIONS: Ultrasonographic measurement of arterial stiffness is a sensitive
      technique that can detect vascular damage in children with cardiovascular risk
      factors earlier than intima-media thickness measurement.

PMID- 21070720
TI  - Effect on cardiovascular risk of an intervention by family physicians to promote
      physical exercise among sedentary individuals.
AB  - INTRODUCTION AND OBJECTIVES: To evaluate the effect of a program promoting
      physical activity (PEPAF) implemented by family physicians on cardiovascular risk
      reduction. METHODS: The cluster randomized clinical trial involved 56 family
      physicians randomly allocated to an intervention group (n=29) and a control group
      (n=27). Of the patients recruited, only those aged 30-74 years (1915 PEPAF and
      1783 control) were included in the analysis. The intervention involved giving
      general advice about the benefits of physical activity to all patients and
      prescribed advice to a subgroup of patients (30%) who agreed to an additional
      consultation. Outcome measures included risk factors and cardiovascular risk
      assessed using the Framingham-D'Agostino scale. RESULTS: A significant decrease
      from baseline in systolic and diastolic blood pressure and pulse pressure was
      observed after 12 months in both groups (control group: -2.93 mmHg, -1.81 mmHg
      and -1.15 mmHg, respectively; PEPAF group: -3.35 mmHg, -1.4 mmHg, and -1.94 mmHg,
      respectively). The high-density lipoprotein cholesterol level increased (control
      group: +1.73 mg/dl; PEPAF group: +2.67 mg/dl), while the atherogenic index
      decreased (by 0.12 and 0.16 in the two groups, respectively), all from baseline
      (P< .05). Cardiovascular risk decreased by 0.68 (95% confidence interval [CI],
      0.13-1.25) in the control group and 0.79 (95%CI, 0.22-1.35) in the PEPAF group.
      There was no significant difference in the improvement at 12 months between the
      groups. CONCLUSIONS: Patients' participation in the project was effective in
      improving control of risk factors and decreasing cardiovascular risk. No
      significant difference in outcome was observed between the control group and the
      group participating in the program promoting physical activity.

PMID- 21070722
TI  - The epidemiology of cardiovascular disease in primary care. the Zona Franca
      Cohort study in Barcelona, Spain.
AB  - INTRODUCTION AND OBJECTIVES: Knowledge about the incidence of cardiovascular
      disease in Spain is limited, particularly about emergent conditions such as
      peripheral arterial disease and heart failure. The objective of this study was to
      determine the incidence of these conditions in a primary care setting. METHODS: A
      prospective population-based cohort study was carried out in two health centers
      in Barcelona, Spain. It included 931 randomly selected individuals, aged 35 to 84
      years, without cardiovascular disease who were followed for 10 years. We assessed
      the incidence of ischemic heart disease (i.e. myocardial infarction and angina),
      cerebrovascular disease (i.e. stroke and transient ischemic attack), peripheral
      arterial disease of the lower extremities, and heart failure. RESULTS: The most
      frequently occurring condition was ischemic heart disease (cumulative incidence,
      6.1%), followed by cerebrovascular disease (4.3%), heart failure (3.0%), and
      peripheral arterial disease (1.9%). These conditions were more frequent in
      patients aged >65 years (cumulative incidence, 9.6%, 8.9%, 4.6% and 3.1%,
      respectively). The most frequent comorbid conditions were ischemic heart disease
      and cerebrovascular disease. The incidence of acute myocardial infarction was
      greater in men (P< .001), but there was no significant difference for other
      conditions. The adjusted incidence (European population) per 100,000 inhabitants
      per year in men and women, respectively, was: 605 and 115 for acute myocardial
      infarction; 238 and 220 for angina; 300 and 327 for stroke; 125 and 115 for
      transient ischemic attack; 136 and 178 for peripheral arterial disease; and 219
      and 267 for heart failure. CONCLUSIONS: The incidence of cardiovascular disease
      was lower than in other developed countries. Disease occurred more frequently in
      patients aged >65 years. Ischemic heart disease remained the most common, with
      heart failure being a notable emergent condition.

PMID- 21070723
TI  - Prognostic value of resting heart rate in a broad population of patients with
      stable coronary artery disease: prospective single-center cohort study.
AB  - INTRODUCTION AND OBJECTIVES: Our aim was to investigate the prognostic value of
      the resting heart rate (RHR) in a broad unselected population of patients with
      stable coronary artery disease (sCAD). METHOD: Between February 1, 2000 and
      January 31, 2004, 1264 ambulatory patients with sCAD were recruited into the
      prospective study. Patients were followed up for major events (i.e. death, acute
      coronary syndrome, coronary revascularization, stroke, and hospitalization for
      heart failure). Associations between these events and the RHR (i.e. >= 70 beats
      per minute [bpm] versus < 70 bpm) were evaluated. RESULTS: The patients' median
      age was 68 years (interquartile range [IQR] 60-74 years) and 926 (73%) were male.
      The RHR was >= 70 bpm in 645 patients (51%) and < 70 bpm in 619 (49%). After a
      median follow-up period of 25 months (IQR 12-39 months), with only seven patients
      lost to follow-up, the probability of an event was 17.48% in patients with an RHR
      >= 70 bpm and 17.67% in those with an RHR < 70 bpm (P =. 32) and total mortality
      was 2.32% and 2.5%, respectively (P = .56). After adjustment for age, sex,
      cardiovascular risk factors, blood pressure, baseline cardiac rhythm, ejection
      fraction and treatment at first visit, no significant association was found
      between the RHR and major events (hazard ratio [HR] = 1.04; 95% confidence
      interval [CI], 0.76-1.43; P = .79) or mortality (HR = 1.24; 95% CI, 0.55-2.81;
      P=.61). CONCLUSIONS: The RHR was not an adverse prognostic factor in this group
      of unselected patients with sCAD. The prognostic value of the RHR in daily
      clinical practice could be low in this population.

PMID- 21070724
TI  - Characterizing myocardial deformation in patients with left ventricular
      hypertrophy of different etiologies using the strain distribution obtained by
      magnetic resonance imaging.
AB  - INTRODUCTION AND OBJECTIVES: In hypertrophic cardiomyopathy (HCM), it has been
      suggested that regional fiber disarray produces segments that exhibit no or
      severely reduced deformation, and that these segments are distributed
      nonuniformly within the left ventricle (LV). This contrasts with observations in
      other types of hypertrophy, such as in athlete's heart or hypertensive left
      ventricular hypertrophy (HLVH), in which abnormal cardiac deformation may exist
      but the reduction is not so severe that some segments exhibit no deformation. Our
      aim was to use the strain distribution to study deformation in HCM. METHODS: We
      used tagged magnetic resonance imaging to reconstruct LV systolic deformation in
      12 controls, 10 athletes, 12 patients with HCM, and 10 patients with HLVH.
      Deformation was quantified using a fast nonrigid registration algorithm and peak
      radial and circumferential systolic strain values were determined in 16 LV
      segments. RESULTS: Patients with HCM had significantly lower average strain
      values than individuals in other groups. However, while the deformation observed
      in healthy subjects and HLVH patients clustered around the mean, in HCM patients,
      segments with normal contraction coexisted with segments exhibiting no or
      significantly reduced deformation, which resulted in a greater heterogeneity of
      strain values. Moreover, some nondeforming segments were observed even when
      fibrosis and hypertrophy were absent. CONCLUSIONS: The strain distribution
      characterized specific patterns of myocardial deformation in patients with LVH
      due to different etiologies. Patients with HCM had significantly lower mean
      strain values and a greater heterogeneity in strain values than controls,
      athletes and HLVH patients. In addition, they had nondeforming regions.

PMID- 21070725
TI  - Summary of the clinical studies reported in the European Society of Cardiology
      Congress 2010 (August 28-September 1, 2010, Stockholm, Sweden).

PMID- 21070726
TI  - Spanish Cardiac Catheterization and Coronary Intervention Registry. 19th Official
      Report of the Spanish Society of Cardiology Working Group on Cardiac
      Catheterization and Interventional Cardiology (1990-2009).
AB  - INTRODUCTION AND OBJECTIVES: Each year the Spanish Society of Cardiology Working
      Group on Cardiac Catheterization and Interventional Cardiology reports on the
      data collected by the national registry of procedures performed. This report
      covers 2009. It contains information on the implementation of interventional
      cardiology across Spain and enables comparisons to be made with other countries.
      METHODS: Data were provided voluntarily and were analyzed by the Working Group's
      steering committee. RESULTS: Data were submitted by 126 hospitals that mainly
      performed procedures in adults: 74 public and 52 private. Overall, 137,166
      diagnostic procedures were carried out, including 122,961 coronary angiograms;
      the rate of 2664 coronary angiograms per million population was little changed
      from the previous year. The number of percutaneous coronary interventions
      increased by 2% to reach 63,075, which corresponds to 1391 per million
      population. In total, 102,850 stents were implanted (58.7% drug-eluting). In
      addition, 13,395 interventions were carried out during the acute phase of
      myocardial infarctions: this represents a 10% increase relative to 2008 and
      accounts for 21% of all percutaneous coronary interventions. The most frequent
      intervention for adult congenital heart disease was closure of an atrial septal
      defect, with 329 procedures. The most frequently performed valve procedure was
      mitral valvuloplasty, with 336 cases treated (success rate 96%), with the
      exception of percutaneous aortic valve implantation, which increased
      exponentially to a total of 426 in 2009. CONCLUSIONS: The most significant
      increases in activity were in procedures for ST-segment elevation acute
      myocardial infarction and in percutaneous valve implantation. There was only a
      modest increase in the use of all other diagnostic and therapeutic procedures.

PMID- 21070727
TI  - Spanish Heart Transplantation Registry. 21st Official Report of the Spanish
      Society of Cardiology Working Group on Heart Failure and Heart Transplantation
      (1984-2009).
AB  - INTRODUCTION AND OBJECTIVES: The purpose of this report is to present the results
      obtained with heart transplantation in Spain from the first use of this
      therapeutic modality in May 1984. METHODS: A descriptive analysis of all heart
      transplantations performed up to December 31, 2009 is presented. RESULTS: In
      total, 6048 transplants were carried out. The typical clinical profile of a
      Spanish heart transplant patient in 2009 was that of a 53-year-old male who had
      been diagnosed with nonrevascularizable ischemic heart disease and who had
      severely impaired ventricular function and a poor functional status. The
      implanted heart typically came from a donor who had died from a brain hemorrhage
      (mean age 37 years) and the average time on the waiting list was 106 days. Mean
      survival time has increased progressively over the years. Whereas for the whole
      time series, the probability of survival at 1, 5, 10 and 15 years was 78%, 67%,
      53% and 40%, respectively, for the past 5 years, the probability of survival at 1
      and 5 years was 85% and 73%, respectively. The most frequent cause of death was
      acute graft failure (17%), followed by infection (16%), the combination of graft
      vascular disease and sudden death (14%), tumor (12%) and acute rejection (8%).
      CONCLUSIONS: The survival rates obtained in Spain with heart transplantation,
      especially in recent years, make the procedure the treatment of choice for
      patients who have irreversible heart failure and a poor functional status and for
      whom there are few other established medical or surgical options.

PMID- 21070728
TI  - Spanish Catheter Ablation Registry. 9th Report of the Spanish Society Of
      Cardiology Working Group on Electrophysiology and Arrhythmias (2009).
AB  - INTRODUCTION AND OBJECTIVES: This article reports the findings of the 2009
      Spanish national Catheter Ablation Registry. METHODS: Data were collected in two
      ways: retrospectively using a standard questionnaire and prospectively from a
      central database. Each center chose its own preferred method of data collection.
      RESULTS: Data were collected from 59 centers. The total number of ablation
      procedures carried out was 8546, giving a mean of 145 +/- 101 procedures per
      center. The three most frequently treated conditions were atrioventricular nodal
      reentrant tachycardia (n = 2341; 27%), typical atrial flutter (n = 1859; 21.7%)
      and accessory pathways (n = 1758; 20.5%). The fourth most common condition was
      atrial fibrillation (n = 1188; 14%), the number of which has grown by 44% since
      the 2008 registry. The overall success rate was 93%, major complications occurred
      in 1.9%, and the mortality rate was 0.046%. CONCLUSIONS: Data from the 2009
      registry show that the number of ablations carried out continued to increase and
      exceeded 8000 for the first time. In addition, they show, in general, a higher
      success rate and a lower number of complications. Cavotricuspid isthmus ablation,
      as treatment for typical atrial flutter, continued to be the second most common
      procedure. There was a substantial increase in the number of catheter ablations
      performed for atrial fibrillation compared with previous years.

PMID- 21070729
TI  - Stagnant in cardiovascular prevention: alarming trends and persistent
      socioeconomic obstacles.
AB  - Recently it has been suggested that the decline in cardiovascular mortality
      observed over the last 50 years may be coming to an end. This alarming trend,
      which has been noted mainly in younger adults from lower socioeconomic strata,
      may be linked to other changes, namely the increasing prevalence of modifiable
      risk factors, the most important of which is obesity. In contrast, our ability to
      predict cardiovascular risk continues to improve steadily, although it is unclear
      which will be its ability in designing more effective global preventive measures.
      Coronary heart disease appears to develop through multiple pathways, whose
      association with cardiovascular risk is mediated by complex processes involving
      numerous factors ranging from genetic predisposition to unfavorable socioeconomic
      circumstances. Although some attention has been paid to the latter, more effort
      has been put into controlling isolated risk factors. For example, numerous large
      studies have involved looking at the effect of single-drug therapies aimed at
      specific targets rather than examining more comprehensive approaches to managing
      multiple risk factors. In conclusion, an effective strategy for controlling
      modifiable risk factors in both individuals and populations must address this
      complex scenario and should consider significant socioeconomic factors such as
      education, income and the built environment. The unfavorable trend observed in
      cardiovascular health makes it essential that current preventive strategies are
      reassessed.

PMID- 21070730
TI  - Tricuspid and pulmonary valve disease evaluation and management.
AB  - The clinical detection and quantification of tricuspid valve disease, although
      important, is not entirely accurate. Diagnostic evaluation is based on
      echocardiography, and color flow Doppler is useful for quantifying tricuspid
      regurgitation. Echocardiography provides information on heart chamber dimensions,
      right ventricular function, and the degree of pulmonary hypertension. In
      addition, tricuspid stenosis can be accurately assessed using mean and end
      diastolic pressure gradient measurements. The treatment options for tricuspid
      stenosis include balloon valvuloplasty and surgical valve repair. Functional
      tricuspid regurgitation associated with left heart disease may require surgical
      attention during an operation to treat the left heart disease. Severe tricuspid
      regurgitation usually requires surgery to be performed in association with mitral
      valve surgery. Mild-to-moderate tricuspid regurgitation requires surgery when
      annular dilatation or severe pulmonary hypertension is present. The surgical
      options include tricuspid valve repair, with or without an annuloplasty ring. In
      patients with a primary anatomic deformity of the tricuspid valve, replacement of
      the valve with a bioprosthesis or mechanical valve may be considered.
      Intermediate and long-term results favor annuloplasty valve repair over valve
      replacement. Pulmonary valve disease is predominantly congenital, and generally
      takes the form of pulmonary stenosis. Pulmonary regurgitation often results from
      surgical or balloon valvuloplasty and is associated with deleterious long-term
      sequelae. The recent development of percutaneous valve replacement was a major
      advance.

PMID- 21070731
TI  - Aortic thrombus and acute pulmonary embolism in an individual heterozygous for
      the MTHFR C677T mutation.

PMID- 21070732
TI  - Complex aortic coarctation and PHACE syndrome.
AB  - In PHACE syndrome, the acronym PHACE stands for the association of posterior
      fossa malformations, cervicofacial hemangiomas, arterial anomalies, coarctation
      and eye anomalies. We report our findings in four patients with this syndrome, in
      whom it was characterized by complex aortic coarctation that required not only
      preoperative echocardiographic investigation, but also the use of techniques such
      as magnetic resonance imaging and angiography. Surgical treatment was also
      complex. Prognosis in this condition depends primarily on cardiovascular and
      cerebral artery complications associated with the syndrome.

PMID- 21070734
TI  - White-coat hypertension in the elderly. Echocardiographic analysis. A substudy of
      the EPICARDIAN project.
AB  - The aims of this study were to investigate echocardiographic abnormalities in the
      elderly and to evaluate differences between those who are normotensive and those
      who have white-coat hypertension or sustained hypertension. The study used data
      on a subsample of participants in the EPICARDIAN project who came from the Lista
      district of Madrid, Spain. Of the 271 included, 61 (22.5%) were normotensive, 81
      (29.9%) had white-coat hypertension and 129 (49.6%) had sustained hypertension.
      The left ventricular mass index was significantly different between the
      subgroups: 94.9 g/m2 in normotensives, 125.6 g/m2 in those with white-coat
      hypertension and 136.3 g/m2 in those with sustained hypertension (P< .001). The
      prevalence of left ventricular hypertrophy, defined using Deveraux's criteria,
      was 13.2% in normotensives, 49.1% in those with white-coat hypertension and 54.3%
      in those with sustained hypertension (P=.00007). White-coat hypertension is not a
      innocuous finding in the elderly because its implications for cardiac health are
      closer to those of sustained hypertension than to those of normal blood pressure.

PMID- 21070733
TI  - Effect of diabetes on the clinical characteristics and prognosis of patients with
      chronic ischemic heart disease. The CIBAR study.
AB  - The aim of this study was to evaluate the effect of diabetes mellitus on the
      prognosis of patients with chronic ischemic heart disease. The multicenter
      prospective cohort study involved 1108 outpatients with ischemic heart disease
      whose clinical characteristics were recorded by 69 primary care physicians.
      Morbidity and mortality were recorded during a mean follow-up period of 6.9
      months. Overall, 29% of patients were diabetic; they were older than non
      diabetics, presented with more risk factors, had poorer blood pressure control,
      and had more comorbid conditions. In addition, diabetics were more likely to be
      prescribed renin-angiotensin system blockers, calcium channel blockers, diuretics
      and lipid-lowering drugs. Cardiovascular mortality and hospitalization rates were
      higher in diabetics. On multivariate analysis, diabetes was found to be an
      independent predictor of a cardiovascular event (hazard ratio=1.81; 95%
      confidence interval, 1.17-2.82). Prognosis in chronic ischemic heart disease is
      relatively good, although it is worse in diabetics, which means that treatment
      and disease controls targets must be more rigorously applied in these patients.

PMID- 21070735
TI  - Tissue characterization of a primary cardiac angiosarcoma using magnetic
      resonance imaging.

PMID- 21070736
TI  - Metalloproteinase polymorphisms and bicuspid aortic valves.

PMID- 21070737
TI  - Use of a second device for the closure of patent foramen ovale.

PMID- 21070738
TI  - Myocarditis due to pandemic influenza A (H1N1).

PMID- 21070739
TI  - Validation and applicability of a risk score: the more data, the better.

PMID- 21070744
TI  - Retro-inversion of certain cell-penetrating peptides causes severe cellular
      toxicity.
AB  - Cell-penetrating peptides (CPPs) are a promising group of delivery vectors for
      various therapeutic agents but their application is often hampered by poor
      stability in the presence of serum. Different strategies to improve peptide
      stability have been exploited, one of them being "retro-inversion" (RI) of
      natural peptides. With this approach the stability of CPPs has been increased,
      thereby making them more efficient transporters. Several RI-CPPs were here
      assessed and compared to the corresponding parent peptides in different cell
      lines. Surprisingly, treatment of cells with these peptides induced trypsin
      insensitivity and rapid severe toxicity in contrast to L-peptides. This was
      measured as reduced metabolic activity and condensed cell nuclei, in parity with
      the apoptosis inducing agent staurosporine. Furthermore, effects on mitochondrial
      network, focal adhesions, actin cytoskeleton and caspase-3 activation were
      analyzed and adverse effects were evident at 20 MUM peptide concentration within
      4 h while parent L-peptides had negligible effects. To our knowledge this is the
      first time RI peptides are reported to cause cellular toxicity, displayed by
      decreased metabolic activity, morphological changes and induction of apoptosis.
      Considering the wide range of research areas that involves the use of RI
      peptides, this finding is of major importance and needs to be taken under
      consideration in applications of RI-peptides.

PMID- 21070745
TI  - A site-specific genomic integration strategy for sustained expression of glucagon
      like peptide-1 in mouse muscle for controlling energy homeostasis.
AB  - The incretin hormone glucagon-like peptide-1 (GLP-1) exerts important functions
      in controlling glucose and energy homeostasis. Endogenous GLP-1 has a very short
      half-life due to DPP-IV-mediated degradation and renal clearance, which limits
      the therapeutic use of native GLP-1. We have shown previously that immunoglobulin
      fragment-fused GLP-1 (GLP-1/Fc) is a structurally stable GLP-1 analog. Here, we
      report a non-viral GLP-1/Fc gene therapy strategy utilizing a REP78-in-trans and
      REB-in-cis element system to achieve a site-specific genomic integration. For
      this purpose, the GLP-1/Fc expression cassette, which is fused with the RBE
      element, was co-injected with the Rep78 plasmid into the muscles of transgenic
      mice carrying the AAVS1 locus of human chromosome 19. The Rep protein-mediated
      site-specific integration was demonstrated by nested PCR, dot-blot, and Southern
      blotting. We found that this approach reduced weight gain and improved lipid
      profiles in the AAVS1-mice on high-fat diet challenge. Our observations reveal a
      new GLP-1 therapeutic strategy with an apparent absence of side effects, which
      may find applications in diabetes treatment and obesity prevention.

PMID- 21070746
TI  - Thermal-induced conformational changes in the product release area drive the
      enzymatic activity of xylanases 10B: Crystal structure, conformational stability
      and functional characterization of the xylanase 10B from Thermotoga petrophila
      RKU-1.
AB  - Endo-xylanases play a key role in the depolymerization of xylan and recently,
      they have attracted much attention owing to their potential applications on
      biofuels and paper industries. In this work, we have investigated the molecular
      basis for the action mode of xylanases 10B at high temperatures using
      biochemical, biophysical and crystallographic methods. The crystal structure of
      xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1
      (TpXyl10B) has been solved in the native state and in complex with xylobiose. The
      complex crystal structure showed a classical binding mode shared among other
      xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B
      displayed a temperature-dependent action mode producing xylobiose and xylotriose
      at 20 degrees C, and exclusively xylobiose at 90 degrees C as assessed by
      capillary zone electrophoresis. Moreover, circular dichroism spectroscopy
      suggested a coupling effect of temperature-induced structural changes with this
      particular enzymatic behavior. Molecular dynamics simulations supported the CD
      analysis suggesting that an open conformational state adopted by the catalytic
      loop (Trp297-Lys326) provokes significant modifications in the product release
      area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific
      release of xylobiose at high temperatures.

PMID- 21070747
TI  - CYP1D1, pseudogenized in human, is expressed and encodes a functional drug
      metabolizing enzyme in cynomolgus monkey.
AB  - Cytochrome P450 (P450 or CYP) 1 family consists of the CYP1A, CYP1B, CYP1C, and
      CYP1D subfamilies. In the human genome, CYP1A1, CYP1A2, and CYP1B1 are expressed
      and encode functional enzymes, whereas CYP1D1P (formerly known as CYP1A8P) is
      present as a pseudogene due to five nonsense mutations in the putative coding
      region. In this study, we identified CYP1D1 cDNA, highly identical (nearly 95%)
      to human CYP1D1P sequence, in cynomolgus monkey, a species frequently used in
      drug metabolism studies due to its evolutionary closeness to human. The amino
      acid sequence deduced from cynomolgus monkey CYP1D1 cDNA shared the high sequence
      identity (91%) with human CYP1D1P (postulated from the gene sequence), and the
      highest sequence identity (44-45%) with CYP1A1 and CYP1A2 among cynomolgus monkey
      P450s. CYP1D1 mRNA was most abundantly expressed in liver, followed by kidney,
      and jejunum. The hepatic expression level of CYP1D1 mRNA was comparable to that
      of CYP1A1 mRNA and much higher than that of CYP1A2 mRNA. CYP1D1 was barely
      detectable in immunoblots of cynomolgus monkey liver. Cynomolgus monkey CYP1D1
      mRNA was induced in primary hepatocytes with omeprazole. Cynomolgus monkey CYP1D1
      protein heterologously expressed in Escherichia coli catalyzed ethoxyresorufin O
      deethylation and caffeine 8-hydroxylation, which CYP1As also catalyze. Finally,
      no nonsense mutations, corresponding to those found in human CYP1D1P, were found
      in the 20 cynomolgus monkeys and 10 rhesus monkeys used in this study. These
      results suggest that CYP1D1 plays a role as a functional, drug-metabolizing
      enzyme in cynomolgus monkey liver.

PMID- 21070748
TI  - The role of CYP3A4 in amiodarone-associated toxicity on HepG2 cells.
AB  - Amiodarone is a class III antiarrhythmic drug with potentially life-threatening
      hepatotoxicity. Recent in vitro investigations suggested that the mono-N-desethyl
      (MDEA) and di-N-desethyl (DDEA) metabolites may cause amiodarone's
      hepatotoxicity. Since cytochrome P450 (CYP) 3A4 is responsible for amiodarone N
      deethylation, CYP3A4 induction may represent a risk factor. Our aim was therefore
      to investigate the role of CYP3A4 in amiodarone-associated hepatotoxicity. First,
      we showed that 50MUM amiodarone is more toxic to primary human hepatocytes after
      CYP induction with rifampicin. Second, we overexpressed human CYP3A4 in HepG2
      cells (HepG2 cells/CYP3A4) for studying the interaction between CYP3A4 and
      amiodarone in more detail. We also used HepG2 wild type cells (HepG2 cells/wt) co
      incubated with human CYP3A4 supersomes for amiodarone activation (HepG2
      cells/CYP3A4 supersomes). Amiodarone (10-50MUM) was cytotoxic for HepG2
      cells/CYP3A4 or HepG2 cells/CYP3A4 supersomes, but not for HepG2 cells/wt or less
      toxic for HepG2 cells/wt incubated with control supersomes without CYP3A4. Co
      incubation with ketoconazole, attenuated cytotoxicity of amiodarone incubated
      with HepG2 cells/CYP3A4 or HepG2 cells/CYP3A4 supersomes. MDEA and DDEA were
      formed only in incubations containing HepG2 cells/CYP3A4 or HepG2 cells/CYP3A4
      supersomes but not by HepG2 cells/wt or HepG2 cells/wt with control supersomes.
      Metabolized amiodarone triggered the production of reactive oxygen species,
      induced mitochondrial damage and cytochrome c release, and promoted
      apoptosis/necrosis in HepG2 cells/CYP3A4, but not HepG2 cells/wt. This study
      supports the hypothesis that a high CYP3A4 activity is a risk factor for
      amiodarone's hepatotoxicity. Since CYP3A4 inducers are used frequently and
      amiodarone-associated hepatotoxicity can be fatal, our observations may be
      clinically relevant.

PMID- 21070749
TI  - Prostaglandin E2 regulates cellular migration via induction of vascular
      endothelial growth factor receptor-1 in HCA-7 human colon cancer cells.
AB  - An important event in the development of tumors is angiogenesis, or the formation
      of new blood vessels. Angiogenesis is also known to be involved in tumor cell
      metastasis and is dependent upon the activity of the vascular endothelial growth
      factor (VEGF) signaling pathway. Studies of mice in which the EP3 prostanoid
      receptors have been genetically deleted have shown a role for these receptors in
      cancer growth and angiogenesis. In the present study, human colon cancer HCA-7
      cells were used as a model system to understand the potential role of EP3
      receptors in tumor cell migration. We now show that stimulation of HCA-7 cells
      with PGE2 enhanced the up-regulation of VEGF receptor-1 (VEGFR-1) expression by a
      mechanism involving EP3 receptor-mediated activation of phosphatidylinositol 3
      kinase and the extracellular signal-regulated kinases. Moreover, the PGE2
      stimulated increase in VEGFR-1 expression was accompanied by an increase in the
      cellular migration of HCA-7 cells. Given the known involvement of VEGFR-1 in
      cellular migration, our results suggest that EP3 receptors may contribute to
      tumor cell metastasis by increasing cellular migration through the up-regulation
      of VEGFR-1 signaling.

PMID- 21070750
TI  - Reproducibility and variance of a stimulation-induced hemodynamic response in
      barrel cortex of awake behaving mice.
AB  - The present work evaluated the reproducibility and variance of the cerebral blood
      flow (CBF) response to natural whisker stimulation in the barrel cortex of awake
      behaving mice. The animal was placed on an air float ball that allowed the animal
      to walk, while the head of the animal was fixed in a custom-made stereotactic
      apparatus. Dynamic CBF changes in the barrel cortex and animal locomotion were
      simultaneously monitored with laser-Doppler flowmetry (LDF) and an optical motion
      sensor that detected the rotation distance of the ball, respectively. Whisker
      stimulation-induced CBF measured under daytime and nighttime conditions showed
      consistent responses (24% and 23% of the pre-stimulus baseline, respectively),
      whereas the amount of locomotion was 1.4 times higher during nighttime relative
      to daytime. Repeated longitudinal experiments over 7 days showed a reproducible,
      evoked CBF (13-26% relative to the baseline among 7 animals). The mean of the
      variance coefficient (i.e., standard deviation divided by mean) across multiple
      days was 0.11 and 0.75 for evoked CBF and locomotion, respectively. These results
      showed reproducible and reliable measurements of longitudinal CBF response in
      behaving mice regardless of day-to-day variations in locomotion. Furthermore, we
      confirmed that the CBF response to whisker stimulation was well localized and
      reproducible, measured with laser speckle imaging under awake condition. The
      results further show the capability of long-term hemodynamic imaging in normal
      and disease-model mice, which is of particular importance for understanding the
      longitudinal changes and plasticity of neurovascular coupling and behavioral
      performances such as during growth, development and aging.

PMID- 21070752
TI  - Increase of mushroom spine density in CA1 apical dendrites produced by water maze
      training is prevented by ovariectomy.
AB  - Dendritic spine density increases after spatial learning in hippocampal CA1
      pyramidal neurons. Gonadal activity also regulates spine density, and abnormally
      low levels of circulating estrogens are associated with deficits in hippocampus
      dependent tasks. To determine if gonadal activity influences behaviorally induced
      structural changes in CA1, we performed a morphometric analysis on rapid Golgi
      stained tissue from ovariectomized (Ovx) and sham-operated (Sham) female rats 7
      days after they were given a single water maze (WM) training session (hidden
      platform procedure) or a swimming session in the tank containing no platform
      (SC). We evaluated the density of different dendritic spine types (stubby, thin,
      and mushroom) in three segments (distal, medial, and proximal) of the principal
      apical dendrite from hippocampal CA1 pyramidal neurons. Performance in the WM
      task was impaired in Ovx animals compared to Sham controls. Total spine density
      increased after WM in Sham animals in the proximal and distal CA1 apical dendrite
      segments but not in the medial. Interestingly, mushroom spine density
      consistently increased in all CA1 segments after WM. As compared to the Sham
      group, SC-Ovx rats showed spine pruning in all the segments, but mushroom spine
      density did not change significantly. In Ovx rats, WM training increased the
      density of stubby and thin, but not mushroom spines. Thus, ovariectomy alone
      produces spine pruning, while spatial learning increases spine density in spite
      of ovariectomy. Finally, the results suggest that mushroom spine production in
      CA1 after spatial learning requires gonadal activity, whereas this activity is
      not required for mushroom spine maintenance.

PMID- 21070751
TI  - I. Levels of 5alpha-reduced progesterone metabolite in the midbrain account for
      variability in reproductive behavior of middle-aged female rats.
AB  - At middle-age, the reproductive capacity of female rats begins to decline.
      Whether there are consequences for social and reproductive behaviors related to
      changes in estradiol (E(2)), progesterone (P(4)) and its 5alpha-reduced
      metabolites, dihydroprogesterone (DHP) and 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP), is of interest. In Experiment 1, 1-year-old female breeder
      rats that had "maintained their reproductive status" (having 4-5 days estrous
      cycles, > 60% successful pregnancies after mating, > 10 pups/litter) or their age
      matched counterparts with "declining reproductive status" were assessed in social
      interaction, standard mating, and paced mating when in proestrus. Rats that
      maintained reproductive status tended to have higher levels of proceptivity, and
      significantly reduced aggression, towards males, compared to rats with declining
      reproductive status. Basal midbrain E(2) and DHP levels accounted for a
      significant proportion of variance in lordosis. In Experiment 2, 1-year-old, age
      matched, female breeders that had maintained reproductive status or were in
      reproductive decline were compared to three-month old, nulliparous females that
      had regular (4-5 days) or irregular estrous cycles. Age did not influence paced
      mating but younger rats had greater diencephalon E(2) than did middle-aged rats.
      After mating, rats with declining/irregular reproductive status had higher P(4)
      and DHP levels in midbrain than did rats with maintaining/regular reproductive
      status, albeit differences in midbrain 3alpha,5alpha-THP were not seen. Middle
      aged rats that maintained reproductive function had greater 3alpha,5alpha-THP
      formation in diencephalon compared to other groups. Thus, age-related changes in
      central progestogen formation in midbrain or diencephalon may contribute to some
      variability in expression of reproductive behaviors.

PMID- 21070753
TI  - Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal
      cord injury.
AB  - Spinal cord injury (SCI) pain in humans is difficult to treat, and the lack of
      valid methods to measure behavior comparable to the complex human pain experience
      preclinically represents an important obstacle to finding better treatments for
      this type of central pain. The place escape/avoidance paradigm (PEAP) relies on
      the active choice of an animal between its natural preference for a dark
      environment or pain relief, and it has been suggested to measure the affective
      motivational component of pain. We have modified the method to a T10 spinal cord
      contusion model (SCC) of at-level central neuropathic pain in Sprague-Dawley
      rats. In order to demonstrate sensitivity to change in escape/avoidance behavior
      and thus the applicability of the PEAP method to predict drug efficacy, we
      investigated the effect of pregabalin (30 mg/kg) treatment in a randomized
      design. SCC animals displayed increased escape/avoidance behavior postinjury,
      indicating at-level mechanical hypersensitivity. Second, we found no correlation
      between state anxiety levels in SCC animals (elevated plus maze) and PEAP
      behavior, suggesting that the PEAP measurement is not biased by differences in
      anxiety levels. Third, we demonstrated a decrease in escape/avoidance behavior in
      response to treatment with the analgesic drug pregabalin. Thus, the PEAP may be
      applicable as a surrogate correlate of human pain. In conclusion, the primary
      finding in this study was a sensitivity to change in escape/avoidance behavior
      induced by pharmacological modulation with analgesics, supporting the use of the
      PEAP as a central outcome measure in preclinical SCI pain research.

PMID- 21070754
TI  - Hemodialysis vascular access thrombosis: The role of factor V Leiden, prothrombin
      gene mutation and ABO blood groups.
AB  - BACKGROUND: Vascular access thrombosis increases morbidity in hemodialysis (HD)
      patients. The aim of this study was to investigate the association between HD
      vascular access thrombosis and mutations in the prothrombin and factor V Leiden
      (FV) genes and ABO blood system. METHODS: This cross-sectional study included 195
      patients with end stage renal disease (ESRD) on HD for more than six months. HD
      patients were allocated into two groups according to the occurrence (cases, N=46)
      or not (controls, N=149) of previous vascular access thrombosis. FV and
      prothrombin gene mutations were investigated by polymerase chain reaction and ABO
      blood group phenotyping was performed by the indirect technique. Univariate
      analysis detected the variables with a trend to be associated with thrombosis and
      was followed by multivariate analysis to define independent predictors of
      vascular access thrombosis. RESULTS: FV Leiden mutation and ABO blood group were
      not associated with vascular access thrombosis, whereas G20210A mutation in the
      prothrombin gene was significantly higher in patients with vascular access
      thrombosis and independently associated with this complication (OR=12.0; CI
      95%=1.8-83.5; p=0.012). CONCLUSIONS: G20210A mutation emerges as an important
      genetic factor predisposing to vascular access thrombosis. The definition of risk
      factors for thrombosis will certainly enable a rational approach for HD patients.

PMID- 21070755
TI  - Analysis of glucocerebrosidase activity in dry blood spots using tandem mass
      spectrometry.
AB  - BACKGROUND: Gaucher disease (GD) is due to deficiency of acid-beta-glucosidase
      (ABG) and comprises a clinical spectrum with variable age of onset and severity.
      We evaluated a tandem mass spectrometry (MS/MS) method to measure ABG activity
      for high through-put screening. METHODS: ABG activity was measured in 3.2 mm
      punches from dry blood spots (DBS). Each punch was incubated for 21 h with the
      substrate D-Glucosyl-beta1-1'-N-dodecanoyl-D-erythro-sphingosine [C12
      glucocerebroside (C(36)H(69)NO(8))] and internal standard N-myristoyl-D-erythro
      sphingosine [C14-ceramide (C(32)H(63)NO(3))]. The product and internal standard
      were quantified using MS/MS. RESULTS: ABG activities in anonymized newborn
      screening samples from NY State were (mean) 22.0 MUmol/h/L+/-(SD) 13.8 MUmol/h/L
      (n=2088, median 19.9 MUmol/h/L, 95%CI 22.59-21.41 MUmol/h/L). The enzymatic
      activity in DBS from 10 treatment naive adult Gaucher patients was less than 4.2
      MUmol/h/L. ABG activity was stable for 3 months at room temperature a 20%
      activity reduction was observed. Inter- and intra-run imprecisions were 8% and
      13.7%, respectively. The limit of detection was 0.75 MUmol/h/L and limit of
      quantification was 1.25 MUmol/h/L. CONCLUSIONS: The measurement of ABG activities
      in DBS using MS/MS is suitable for high-throughput analysis of at-risk
      individuals and potentially for newborn screening for GD.

PMID- 21070756
TI  - Association of MTHFR, MTR, and MTRR polymorphisms with Parkinson's disease among
      ethnic Chinese in Taiwan.
AB  - BACKGROUND: Influence of folate/homocysteine conversion is considered to be
      important in the pathogenesis of Parkinson's disease (PD). However, association
      of the folate metabolic pathway gene polymorphisms with PD susceptibility remains
      unclear. METHODS: To test this possibility in PD, we conducted a hospital-based
      case-control study constituting 211 patients and 218 age- and sex-matched
      controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen
      for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T),
      methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5
      methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR A1049G and
      C1783T) genes and assess the association between these genotype polymorphisms and
      PD risk using logistic regression analysis. RESULTS: Of these four non-synonymous
      polymorphisms, the MTRR 1049GG variant was significantly associated with PD
      susceptibility (OR=3.17, 95%CI=1.08-9.35). Furthermore, we stratified our
      patients based on the MTHFR 677TT genotype in different strata, a significant
      association between the joint effect of polymorphisms and PD risk was observed in
      those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR
      A2756G (P<0.05). CONCLUSION: Our findings provide support for the synergistic
      effects of polymorphisms in the folate metabolic pathway genes in PD
      susceptibility; the increased PD risk would be more significant in carriers with
      the polymorphisms of MTHFR, MTR, and MTRR genes.

PMID- 21070757
TI  - Plasminogen activator inhibitor-1 5G/5G genotype is a protecting factor
      preventing posttransplant diabetes mellitus.
AB  - OBJECTIVE: Plasminogen activator inhibitor 1 (PAI-1) is thought to play a role in
      the pathogenesis of obesity and insulin resistance. A connection between
      gestational diabetes mellitus and the functional -675 PAI-1 genotype has been
      reported. Therefore, we examined the role of the PAI-1 gene polymorphism in
      kidney transplant recipients. METHODS: A total of 376 kidney transplant
      recipients were prospectively screened for posttransplant diabetes mellitus
      (PTDM). Eighty-one (21.5%) patients were diagnosed with PTDM and the other 295
      patients were non-diabetic following kidney transplantation. DNA samples were
      isolated from the sera and analyzed for the functional -675 4G/5G promoter
      polymorphisms of the PAI-1 gene. RESULTS: Kidney transplant recipients with PTDM
      were significantly associated with tacrolimus use (p=0.03), older age (p=0.036),
      and higher body mass index (p=0.001). The genotype distribution was significantly
      different between the patients with PTDM (genotype
      4G/4G:4G/5G:5G/5G=33.3%:60.5%:6.2%) and those without PTDM (genotype
      4G/4G:4G/5G:5G/5G=36.9%:44.1%:19.0%) (p=0.018). Patients with homozygosity for 5G
      had a significantly lower rate of PTDM (aOR, 0.286, p=0.022) and higher
      cumulative event-free probability of time to PTDM (log rank test, p=0.0058).
      CONCLUSION: Homozygosity for the 5G allele of the PAI-1 gene constitutes a
      protecting factor for the development of PTDM. Our findings are similar to a
      previous study on gestational diabetes mellitus, and strongly support a possible
      genetic role of PAI-1 in the development of PTDM.

PMID- 21070759
TI  - Lipid emulsion solution: A novel cause of hemolysis in serum and plasma blood
      samples.
AB  - OBJECTIVES: After several hemolyzed blood samples were received in the
      laboratory, we investigated lipid emulsion/TPN as a novel cause of hemolysis.
      DESIGN AND METHODS: Whole blood was spiked with lipid emulsion and TPN. RESULTS:
      Hemolysis was proportional to the amount of lipid emulsion present in whole
      blood, with less hemolysis occurring in blood gas syringes compared to vacutainer
      tubes. CONCLUSION: Collection of specimens in blood gas syringes may prevent
      hemolysis in patients on lipid emulsion.

PMID- 21070758
TI  - Relationship between metabolic disorders and relative risk values of brain
      infarction estimated by protein-conjugated acrolein, IL-6 and CRP together with
      age.
AB  - BACKGROUND: We have recently found that the median relative risk value (RRV) (0
      1) of brain infarction estimated by protein-conjugated acrolein (PC-Acro), IL-6
      and CRP together with age was in the order silent brain infarction (SBI)
      (0.80)>carotid atherosclerosis (CA) (0.76)>white matter hyperintensity (WMH)
      (0.46)>control (0.14). We clarified how metabolic disorders [hypertension (HT),
      hyperlipidemia (HL) and hyperglycemia (HG)] are correlated with RRV. METHODS: The
      levels of PC-Acro, IL-6 and CRP in plasma were measured by ELISA. SBI and WMH
      were evaluated by MRI, and CA was evaluated by duplex carotid ultrasonography.
      RESULTS: The median RRV of metabolic disorders was in the order HT+HG
      (0.84)>HT+HL (0.73)>HT (0.65)~HG (0.65)>HL (0.61)>HL+HG (0.48)>no metabolic
      disorder (0.24)>normal (0.11). Correlation with SBI was in the order HT+HG
      (52%)>HT+HL (42%)>HT (40%)>HG (34%)~HL(33%)>HL+HG (14%)~no metabolic disorder
      (14%). CONCLUSION: The results indicate that HT is the most strongly associated
      factor with SBI among metabolic disorders and that the seriousness of metabolic
      disorder estimated by RRV was well correlated with SBI.

PMID- 21070760
TI  - Changes in pro-oxidant-antioxidant balance after bare metal and drug eluting
      stent implantation in patients with stable coronary disease.
AB  - OBJECTIVES: In this study we aimed to assess the changes in pro-oxidant
      antioxidant balance (PAB) after the placement of either a drug-eluting-stent
      (DES) or bare-metal-stent (BMS) in patients with stable coronary artery disease.
      DESIGN AND METHODS: Percutaneous coronary interventions (PCI) with either BMS or
      DES were undertaken for 152 patients (82 in the BMS and 70 in the DES groups
      respectively). PAB values were measured 24h before and after PCI. RESULTS:
      Baseline PAB values were 80.68 (64.98-99.37) and 98.86 (64.70-140.62) for BMS and
      DES group, respectively, which were not significantly different between the 2
      groups (P>0.05). Following PCI, median PAB values decreased to 72.10 (61.40
      96.13) and 81.40 (54.15-121.90) in BMS and DES groups, respectively. The
      reduction was significant in both BMS and DES groups (P<0.05). The changes in PAB
      values were -2.81 (-12.76 to 2.31) for BMS and -2.82 (-29.88 to 8.93) for DES
      group, which were not significantly different between the 2 groups (P>0.05).
      CONCLUSION: We found that the reported difference in clinical outcomes following
      DES or BMS implantation cannot be attributed to differences in early changes in
      oxidative stress induction as assessed by changes in PAB values.

PMID- 21070762
TI  - Emergence and patterning of the five cell types of the Zea mays anther locule.
AB  - One fundamental difference between plants and animals is the existence of a germ
      line in animals and its absence in plants. In flowering plants, the sexual organs
      (stamens and carpels) are composed almost entirely of somatic cells, a small
      subset of which switch to meiosis; however, the mechanism of meiotic cell fate
      acquisition is a long-standing botanical mystery. In the maize (Zea mays) anther
      microsporangium, the somatic tissues consist of four concentric cell layers that
      surround and support reproductive cells as they progress through meiosis and
      pollen maturation. Male sterility, defined as the absence of viable pollen, is a
      common phenotype in flowering plants, and many male sterile mutants have defects
      in somatic and reproductive cell fate acquisition. However, without a robust
      model of anther cell fate acquisition based on careful observation of wild-type
      anther ontogeny, interpretation of cell fate mutants is limited. To address this,
      the pattern of cell proliferation, expansion, and differentiation was tracked in
      three dimensions over 30 days of wild-type (W23) anther development, using
      anthers stained with propidium iodide (PI) and/or 5-ethynyl-2'-deoxyuridine (EdU)
      (S-phase label) and imaged by confocal microscopy. The pervading lineage model of
      anther development claims that new cell layers are generated by coordinated,
      oriented cell divisions in transient precursor cell types. In reconstructing
      anther cell division patterns, however, we can only confirm this for the origin
      of the middle layer (ml) and tapetum, while young anther development appears more
      complex. We find that each anther cell type undergoes a burst of cell division
      after specification with a characteristic pattern of both cell expansion and
      division. Comparisons between two inbreds lines and between ab- and adaxial
      anther florets indicated near identity: anther development is highly canalized
      and synchronized. Three classical models of plant organ development are tested
      and ruled out; however, local clustering of developmental events was identified
      for several processes, including the first evidence for a direct relationship
      between the development of ml and tapetal cells. We speculate that small groups
      of ml and tapetum cells function as a developmental unit dedicated to the
      development of a single pollen grain.

PMID- 21070761
TI  - Altered intestinal epithelial homeostasis in mice with intestine-specific
      deletion of the Kruppel-like factor 4 gene.
AB  - The zinc finger transcription factor, Kruppel-like factor 4 (KLF4), is expressed
      in the post-mitotic, differentiated epithelial cells lining the intestinal tract
      and exhibits a tumor suppressive effect on intestinal tumorigenesis. Here we
      report a role for KLF4 in maintaining homeostasis of intestinal epithelial cells.
      Mice with conditional ablation of the Klf4 gene from the intestinal epithelium
      were viable. However, both the rates of proliferation and migration of epithelial
      cells were increased in the small intestine of mutant mice. In addition, the
      brush-border alkaline phosphatase was reduced as was expression of ephrine-B1 in
      the small intestine, resulting in mispositioning of Paneth cells to the upper
      crypt region. In the colon of mutant mice, there was a reduction of the
      differentiation marker, carbonic anhydrase-1, and failure of differentiation of
      goblet cells. Mechanistically, deletion of Klf4 from the intestine resulted in
      activation of genes in the Wnt pathway and reduction in expression of genes
      encoding regulators of differentiation. Taken together, these data provide new
      insights into the function of KLF4 in regulating postnatal proliferation,
      migration, differentiation, and positioning of intestinal epithelial cells and
      demonstrate an essential role for KLF4 in maintaining normal intestinal
      epithelial homeostasis in vivo.

PMID- 21070763
TI  - Telencephalic neural precursor cells show transient competence to interpret the
      dopaminergic niche of the embryonic midbrain.
AB  - Neural Precursor Cells (NPCs) generate complex stereotypic arrays of neuronal
      subtypes in the brain. This process involves the integration of patterning cues
      that progressively restrict the fate of specific NPCs. Yet the capacity of NPCs
      to interpret foreign microenvironments during development remains poorly defined.
      The aim of this work was to test the competence of mouse telencephalic NPCs to
      respond to the dopaminergic niche of the mesencephalon. Telencephalic NPCs
      isolated from midgestation mouse embryos (E10.5) and transplanted to age-matched
      mesencephalic explants efficiently differentiated into neurons but were largely
      unable to produce midbrain dopaminergic (mDA) neurons. Instead, E10.5
      telencephalic NPCs behaved as restricted gabaergic progenitors that maintained
      ectopic expression of Foxg1 and Pax6. In contrast, E8.5 telencephalic NPCs were
      able to differentiate into Lmx1a(+)/Foxa2(+)/TH(+) neurons in the dopaminergic
      niche of the mesencephalic explants. In addition, these early telencephalic NPCs
      showed region-dependent expression of Nkx6.1, Nkx2.2 and site-specific
      differentiation into gabaergic neurons within the mesencephalic tissue.
      Significant dopaminergic differentiation of E8.5 telencephalic NPCs was not
      observed after transplantation to E12.5 mesencephalic explants, suggesting that
      inductive signals in the dopaminergic niche rapidly decay after midgestation.
      Moreover, we employed transplantation of embryonic stem cells-derived precursors
      to demonstrate that extinction of inductive signals within the telencephalon lags
      behind the commitment of residing NPCs. Our data indicate that the plasticity to
      interpret multiple instructive niches is an early and ephemeral feature of the
      telencephalic neural lineage.

PMID- 21070764
TI  - Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis
      but not intestinal aganglionosis in Ret Y1062F mutant mice.
AB  - The glial cell line-derived neurotrophic factor (GDNF)/RET tyrosine kinase
      signaling pathway plays crucial roles in the development of the enteric nervous
      system (ENS) and the kidney. Tyrosine 1062 (Y1062) in RET is an
      autophosphorylation residue that is responsible for the activation of the
      PI3K/AKT and RAS/MAPK signaling pathways. Mice lacking signaling via Ret Y1062
      show renal hypoplasia and hypoganglionosis of the ENS although the phenotype is
      milder than the Gdnf- or Ret-deficient mice. Sprouty2 (Spry2) was found to be an
      antagonist for fibroblast growth factor receptor (FGFR) and acts as an inhibitory
      regulator of ERK activation. Spry2-deficient mice exhibit hearing loss and
      enteric nerve hyperplasia. In the present study, we generated Spry2-deficient and
      Ret Y1062F knock-in (tyrosine 1062 is replaced with phenylalanine) double mutant
      mice to see if abnormalities of the ENS and kidney, caused by loss of signaling
      via Ret Y1062, are rescued by a deficiency of Spry2. Double mutant mice showed
      significant recovery of ureteric bud branching and ENS development in the
      stomach. These results indicate that Spry2 regulates downstream signaling
      mediated by GDNF/RET signaling complex in vivo.

PMID- 21070765
TI  - The canonical Wnt/beta-catenin signaling pathway regulates Fgf signaling for
      early facial development.
AB  - The canonical Wnt/beta-catenin signaling pathway has implications in early facial
      development; yet, its function and signaling mechanism remain poorly understood.
      We report here that the frontonasal and upper jaw primordia cannot be formed
      after conditional ablation of beta-catenin with Foxg1-Cre mice in the facial
      ectoderm and the adjacent telencephalic neuroepithelium. Gene expression of
      several cell-survival and patterning factors, including Fgf8, Fgf3, and Fgf17, is
      dramatically diminished in the anterior neural ridge (ANR, a rostral signaling
      center) and/or the adjacent frontonasal ectoderm of the beta-catenin conditional
      mutant mice. In addition, Shh expression is diminished in the ventral
      telencephalon of the mutants, while Tcfap2a expression is less affected in the
      facial primordia. Apoptosis occurs robustly in the rostral head tissues following
      inactivation of Fgf signaling in the conditional mutants. Consequently, the upper
      jaw, nasal, ocular and telencephalic structures are absent, but the tongue and
      mandible are relatively developed in the conditional mutants at birth. Using
      molecular biological approaches, we demonstrate that the Fgf8 gene is
      transcriptionally targeted by Wnt/beta-catenin signaling during early facial and
      forebrain development. Furthermore, we show that conditional gain-of-function of
      beta-catenin signaling causes drastic upregulation of Fgf8 mRNA in the ANR and
      the entire facial ectoderm, which also arrests facial and forebrain development.
      Taken together, our results suggest that canonical Wnt/beta-catenin signaling is
      required for early development of the mammalian face and related head structures,
      which mainly or partly acts through the initiation and modulation of balanced Fgf
      signaling activity.

PMID- 21070766
TI  - The DPP-4 inhibitor vildagliptin increases pancreatic beta cell mass in neonatal
      rats.
AB  - The present study addressed the effect of the dipeptidyl peptidase-4 (DPP-4)
      inhibitor vildagliptin ((1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)
      pyrrolidine), LAF237) on pancreatic beta cell mass in neonatal rats. Newborn rats
      were treated orally with vildagliptin (60 mg/kg) or vehicle once daily for 19
      days starting from postnatal day 2. Pancreatic immunohistochemistry and
      morphometric analysis were performed to evaluate changes in beta cell mass, cell
      apoptosis (Apoptag stain) and replication (5'-Bromo-2'-deoxyuridine (BrdU)
      incorporation) on days 7, 21, and 33. On day 7, an eight-fold increase in BrdU
      positive pancreatic beta cells and a 71% decrease in Apoptag-positive cells were
      observed. On day 21, vildagliptin produced a two-fold increase in pancreatic beta
      cell mass compared to placebo (0.06+/-0.01 mg vs 0.11+/-0.02 mg, P<0.05). Beta
      cell mass remained elevated (90%, 0.09+/-0.02 mg vs 0.16+/-0.03 mg, P<0.05) on
      day 33, twelve days after discontinuing vildagliptin treatment. These data show
      that the DPP-4 inhibitor vildagliptin increased pancreatic beta cell mass through
      enhanced beta cell replication and reduced apoptosis. The increased beta cell
      mass was sustained for 12 days after vildagliptin washout. This study
      demonstrates that DPP-4 inhibitors can elicit beneficial effects on beta cell
      turnover that could help to prevent or retard the progression of type 2 diabetes.

PMID- 21070767
TI  - IGF-I and vitamin C promote myogenic differentiation of mouse and human skeletal
      muscle cells at low temperatures.
AB  - In a previous study investigating the effects of low temperature on skeletal
      muscle differentiation, we demonstrated that C2C12 mouse myoblasts cultured at 30
      degrees C do not express myogenin, a myogenic regulatory factor (MRF), or fuse
      into multinucleated myotubes. At this low temperature, the myoblasts continuously
      express Id3, a negative regulator of MRFs, and do not upregulate muscle-specific
      microRNAs. In this study, we examined if insulin-like growth factor-I (IGF-I) and
      a stable form of vitamin C (L-ascorbic acid phosphate) could alleviate the low
      temperature-induced inhibition of myogenic differentiation in C2C12 cells.
      Although the addition of either IGF-I or vitamin C alone could promote myogenin
      expression in C2C12 cells at 30 degrees C, elongated multinucleated myotubes were
      not formed unless both IGF-I and vitamin C were continuously administered. In
      human skeletal muscle cells, low temperature-induced blockage of myogenic
      differentiation was also ameliorated by exogenous IGF-I and vitamin C. In
      addition, we demonstrated that satellite cells of IGF-I overexpressing transgenic
      mice in single-fiber culture expressed myogenin at a higher level than those of
      wild-type mice at 30 degrees C. This study suggests that body temperature plays
      an important role in myogenic differentiation of endotherms, but the sensitivity
      to low temperature could be buffered by certain factors in vivo, such as IGF-I
      and vitamin C.

PMID- 21070768
TI  - Subtyping of human cellular prion proteins and their differential solubility.
AB  - A human form of a prion disorder is the Creutzfeldt-Jakob disease. A hallmark of
      the disease is the accumulation of misfolded prion proteins (PrP(Sc)), which
      exist as heterogeneous subtypes. PrP(Sc) is formed by protein conversion from the
      host-encoded cellular prion (PrP(C)), which is expressed and modified to various
      isoforms. Little is known about variation in PrP(C); however, it is assumed that
      PrP(C) types play important roles in the formation of PrP(Sc). In this study, we
      separated distinct human PrP(C) subtypes on the basis of differential protein
      solubilities in detergent solutions. Single and sequential application of the
      detergents Triton X-100, octyl-glucopyranoside and CHAPS facilitated high
      solubility of glycosylated PrP(C) isoforms, whereas high proportions of
      nonglycosylated PrP(C) remained non-soluble. Most proteins became highly soluble
      with laurylsarcosine and sodium dodecyl sulphate. Our findings demonstrate that
      the solubility characteristics of heterogeneous PrP(C) overlap in human brains
      and convey distinct solubility subtypes. Differentiation by solubility
      experiments can therefore provide valuable information on prion protein
      composition, facilitate the separation of subtypes, and offer new prospects for
      conversion specificity of distinct isoforms.

PMID- 21070769
TI  - Effects of Ricinus communis oil esters on salivary glands of Rhipicephalus
      sanguineus (Latreille, 1806) (Acari: Ixodidae).
AB  - This study showed the interference of esters extracted from Ricinus communis in
      the secretory cycle of salivary glands of Rhipicephalus sanguineus ticks, which
      consequently caused collateral effects on their feeding process. Ticks attached
      on hosts which were fed with commercial feed containing different concentrations
      of R. communis oil esters suffered damages such as cytoplasmic changes in their
      salivary glands, notably in the acinar cells, impairing the functioning of the
      acini and accelerating the organs degeneration as a whole. It was found that
      esters interfered with the activity of cellular secretion by changing the
      glycoprotein of salivary composition especially in acini II cells. It was also
      shown that the damages caused by esters in the salivary glands cells of these
      ectoparasites increased in higher concentrations of the product and degenerative
      glandular changes were more pronounced.

PMID- 21070770
TI  - Effects of ricinoleic acid esters from castor oil of Ricinus communis on the
      vitellogenesis of Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae)
      ticks.
AB  - This study examines the effects of ricinoleic acid esters from Ricinus communis
      castor oil on the vitellogenesis of Rhipicephalus sanguineus ticks attached to
      hosts that were fed with commercial rabbit food containing these esters. The
      oocytes of ticks from the treatment group (TG) showed cytoplasmic changes that
      inhibited the development of oocytes I and II to the advanced stages (IV and V)
      in addition to preventing the maturation of oocytes V, resulting in small ones.
      In addition, sperm was not observed in ampoules. Our findings confirm the
      acaricide potential of ricinoleic acid esters.

PMID- 21070771
TI  - Leishmania donovani: assessment of leishmanicidal effects of herbal extracts
      obtained from plants in the visceral leishmaniasis endemic area of Bihar, India.
AB  - One obstacle faced in the effective control of visceral leishmaniasis (VL) is the
      limited number of available treatment options. Furthermore, control efforts have
      been hindered further by the emergence of Leishmania resistance to many of the
      available drugs. In this study, we investigated the anti-leishmanial properties
      of 30 medicinally important plants from the VL endemic area of Bihar, India and
      compared them to two available anti-leishmanial drugs (sodium antimony gluconate
      and amphotericin B) and two plant lectins (phytohemagglutinin and concanavalin A)
      on Leishmania donovani promastigotes in vitro at 24 and 48 h after initiation of
      culture. We identified eight plant extracts in addition to phytohemagglutinin and
      amphotericin B that significantly inhibited the growth of promastigotes (p <
      0.03). We further studied the minimum effective concentrations as well as the
      effect on axenic amastigotes viability and the cell cytotoxicity on human
      peripheral blood of four (Agave americana, Azadirachta indica, Eclipta alba and
      Piper longum) of the eight plant extracts that induced significant promastigotes
      killing (p = 0.00098). Effect-based dose finding analysis revealed that the
      threshold concentration of A. americana required to eliminate L. donovani after
      24h was 0.05 mg/ml. A. indica and P. longum plant extracts eliminated L. donovani
      promastigotes after 48 h at concentrations of 0.1 and 0.5mg/ml, respectively. E.
      alba eliminated the promastigotes at a concentration of 0.5mg/ml within 24h. The
      axenic amastigote killing response was 1.90-, 2.52- and 1.3-fold higher than the
      promastigote killing response with A. indica, A. americana and E. alba plant
      extracts, respectively. A. americana and A. indica, respectively, led to
      approximate 2.5- and 1.3-fold declines in mitochondrial dehydrogenase activity
      compared with control. E. alba stimulation resulted in an up-regulation of
      dehydrogenase activity (p = 0.00329). The CSA from P. longum was found to be
      least cytotoxic; the observed difference in mitochondrial activity was
      insignificant (p = 0.16314). Further studies may reveal the pharmacological
      significance of many of the plants with anti-leishmanial properties identified in
      the present study.

PMID- 21070772
TI  - Coilin interacts with Ku proteins and inhibits in vitro non-homologous DNA end
      joining.
AB  - Coilin is a nuclear protein that plays a role in Cajal body formation. The
      function of nucleoplasmic coilin is unknown. Here we report that coilin interacts
      with Ku70 and Ku80, which are major players in the DNA repair process. Ku
      proteins compete with SMN and SmB' proteins for coilin interaction sites. The
      binding domain on coilin for Ku proteins cannot be localized to one discrete
      region, and only full-length coilin is capable of inhibiting in vitro non
      homologous DNA end joining (NHEJ). Since Ku proteins do not accumulate in CBs,
      these findings suggest that nucleoplasmic coilin participates in the regulation
      of DNA repair.

PMID- 21070773
TI  - Per3, a circadian gene, is required for Chk2 activation in human cells.
AB  - PER3 is a member of the PERIOD genes, but does not play essential roles in the
      circadian clock. Depletion of Per3 by siRNA almost completely abolished
      activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human
      cells. In addition, Per3 physically interacted with ATM and Chk2. Per3
      overexpression induced Chk2 activation in the absence of exogenous DNA damage,
      and this activation depended on ATM. Per3 overexpression also led to the
      inhibition of cell proliferation and apoptotic cell death. These combined results
      suggest that Per3 is a checkpoint protein that plays important roles in
      checkpoint activation, cell proliferation and apoptosis.

PMID- 21070775
TI  - Changes in insulin sensitivity and body weight during and after peginterferon and
      ribavirin therapy for hepatitis C.
AB  - BACKGROUND & AIMS: Chronic hepatitis C is associated with an increased prevalence
      of insulin resistance, which might result from liver disease, metabolic factors,
      or the hepatitis C virus (HCV) itself. The effect of antiviral treatment on
      insulin sensitivity is not well-known. We evaluated changes in insulin resistance
      and weight in patients with hepatitis C during and after peginterferon and
      ribavirin therapy. METHODS: Virahep-C was a prospective, multicenter study of a
      48-week course of combination antiviral therapy in patients infected with HCV
      genotype 1. Insulin resistance (IR) was estimated by the homeostasis model
      assessment index (HOMA2-IR) based on fasting glucose and insulin levels. RESULTS:
      Among 341 patients, 40% had insulin resistance (HOMA2-IR > 2.0). The presence of
      insulin resistance was associated with increasing age, body mass index (BMI), and
      fibrosis stage. Among patients with insulin resistance at the start of the trial,
      median decreases in HOMA2-IR values during treatment were 0.74 at 24 weeks and
      0.89 at 48 weeks, whereas BMI decreased by 1.2 and 2.2 at the same time points (P
      < .001 for all). At follow-up, HOMA2-IR and BMI levels returned toward baseline
      values in patients who did not respond or relapsed, but HOMA2-IR values remained
      significantly lower in patients with sustained virologic response (SVR) (P <
      .001), despite increases in BMI. CONCLUSIONS: In patients with HCV genotype 1
      infections, therapy with peginterferon and ribavirin is associated with decreases
      in body weight and insulin resistance. Among patients with insulin resistance
      before treatment, resolution of HCV infection results in sustained improvements
      in the HOMA-IR index, suggesting that HCV could have a direct role in the
      pathogenesis of insulin resistance.

PMID- 21070774
TI  - Morphine induces MU opioid receptor endocytosis in guinea pig enteric neurons
      following prolonged receptor activation.
AB  - BACKGROUND & AIMS: The MU opioid receptor (MUOR) undergoes rapid endocytosis
      after acute stimulation with opioids and most opiates, but not with morphine. We
      investigated whether prolonged activation of MUOR affects morphine's ability to
      induce receptor endocytosis in enteric neurons. METHODS: We compared the effects
      of morphine, a poor MUOR-internalizing opiate, and (D-Ala2,MePhe4,Gly-ol5)
      enkephalin (DAMGO), a potent MUOR-internalizing agonist, on MUOR trafficking in
      enteric neurons and on the expression of dynamin and beta-arrestin
      immunoreactivity in the ileum of guinea pigs rendered tolerant by chronic
      administration of morphine. RESULTS: Morphine (100 MUmol/L) strongly induced
      endocytosis of MUOR in tolerant but not naive neurons (55.7% +/- 9.3% vs 24.2% +/
      7.3%; P < .001) whereas DAMGO (10 MUmol/L) strongly induced internalization of
      MUOR in neurons from tolerant and naive animals (63.6% +/- 8.4% and 66.5% +/-
      3.6%). Morphine- or DAMGO-induced MUOR endocytosis resulted from direct
      interactions between the ligand and the MUOR because endocytosis was not affected
      by tetrodotoxin, a blocker of endogenous neurotransmitter release. Ligand-induced
      MUOR internalization was inhibited by pretreatment with the dynamin inhibitor,
      dynasore. Chronic morphine administration resulted in a significant increase and
      translocation of dynamin immunoreactivity from the intracellular pool to the
      plasma membrane, but did not affect beta-arrestin immunoreactivity. CONCLUSIONS:
      Chronic activation of MUORs increases the ability of morphine to induce MUOR
      endocytosis in enteric neurons, which depends on the level and cellular
      localization of dynamin, a regulatory protein that has an important role in
      receptor-mediated signal transduction in cells.

PMID- 21070776
TI  - Genetic variation in the prostate stem cell antigen gene and upper
      gastrointestinal cancer in white individuals.
AB  - BACKGROUND & AIMS: An association between gastric cancer and the rs2294008 (C>T)
      polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for
      several Asian populations. We set out to determine whether such an association
      exists in white individuals. METHODS: We genotyped 166 relatives of gastric
      cancer patients, including 43 Helicobacter pylori-infected subjects with
      hypochlorhydria and gastric atrophy, 65 infected subjects without these
      abnormalities, 58 H pylori-negative relatives, and 100 population controls.
      Additionally, a population-based study of chronic atrophic gastritis provided 533
      cases and 1054 controls. We then genotyped 2 population-based, case-control
      studies of upper gastrointestinal cancer: the first included 312 gastric cancer
      cases and 383 controls; the second included 309 gastric cancer cases, 159
      esophageal cancer cases, and 211 controls. Odds ratios were computed from
      logistic models and adjusted for confounding variables. RESULTS: Carriage of the
      risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic
      gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9)
      and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was
      strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse
      association was observed between carriage of the risk allele and gastric cardia
      cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI:
      0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9).
      CONCLUSIONS: The rs2294008 polymorphism in PSCA increases the risk of noncardia
      gastric cancer and its precursors in white individuals but protects against
      proximal cancers.

PMID- 21070777
TI  - Rescue of lethal hepatic failure by hepatized lymph nodes in mice.
AB  - BACKGROUND & AIMS: Hepatocyte transplantation is a potential therapeutic approach
      for liver disease. However, most patients with chronic hepatic damage have
      cirrhosis and fibrosis, which limit the potential for cell-based therapy of the
      liver. The development of an ectopic liver as an additional site of hepatic
      function represents a new approach for patients with end-stage liver disease. We
      investigated the development and function of liver tissue in lymph nodes in mice
      with liver failure. METHODS: Hepatocytes were isolated from 8- to 12-week-old
      mice and transplanted by intraperitoneal injection into 8- to 12-week-old
      fumarylacetoacetate hydrolase mice (Fah(-/-)), a model of the human liver disease
      tyrosinemia type I. Survival was monitored and the locations and functions of the
      engrafted liver cells were determined. RESULTS: Lymph nodes of Fah(-/-) mice were
      colonized by transplanted hepatocytes; Fah(+) hepatocytes were detected adjacent
      to the CD45(+) lymphoid cells of the lymphatic system. Ten weeks after
      transplantation, these mice had substantial improvements in serum levels of
      transaminases, bilirubin, and amino acids. Homeostatic expansion of donor
      hepatocytes in lymph nodes rescued the mice from lethal hepatic failure.
      CONCLUSIONS: Functional ectopic liver tissue in lymph nodes rescues mice from
      lethal hepatic disease; lymph nodes therefore might be used as sites for
      hepatocyte transplantation.

PMID- 21070778
TI  - Prostaglandin E2 signaling and bacterial infection recruit tumor-promoting
      macrophages to mouse gastric tumors.
AB  - BACKGROUND & AIMS: Helicobacter pylori infection induces an inflammatory
      response, which can contribute to gastric tumorigenesis. Induction of
      cyclooxygenase-2 (COX-2) results in production of prostaglandin E(2) (PGE(2)),
      which mediates inflammation. We investigated the roles of bacterial infection and
      PGE(2) signaling in gastric tumorigenesis in mice. METHODS: We generated a
      germfree (GF) colony of K19-Wnt1/C2mE mice (Gan mice); these mice develop gastric
      cancer. We examined tumor phenotypes, expression of cytokines and chemokines, and
      recruitment of macrophages. We also investigated PGE(2) signaling through the
      PGE(2) receptor subtype 4 (EP4) in Gan mice given specific inhibitors. RESULTS:
      Gan mice raised in a specific pathogen-free facility developed large gastric
      tumors, whereas gastric tumorigenesis was significantly suppressed in GF-Gan
      mice; reconstitution of commensal flora or infection with Helicobacter felis
      induced gastric tumor development in these mice. Macrophage infiltration was
      significantly suppressed in the stomachs of GF-Gan mice. Gan mice given an EP4
      inhibitor had decreased expression of cytokines and chemokines. PGE(2) signaling
      and bacterial infection or stimulation with lipopolysaccharide induced expression
      of the chemokine C-C motif ligand 2 (CCL2) (which attracts macrophage) in tumor
      stromal cells or cultured macrophages, respectively. CCL2 inhibition suppressed
      macrophage infiltration in tumors, and depletion of macrophages from the tumors
      of Gan mice led to signs of tumor regression. Wnt signaling was suppressed in the
      tumors of GF-Gan and Gan mice given injections of tumor necrosis factor-alpha
      neutralizing antibody. CONCLUSIONS: Bacterial infection and PGE(2) signaling are
      required for gastric tumorigenesis in mice; they cooperate to up-regulate CCL2,
      which recruits macrophage to gastric tumors. Macrophage-derived tumor necrosis
      factor-alpha promotes Wnt signaling in epithelial cells, which contributes to
      gastric tumorigenesis.

PMID- 21070779
TI  - A functional single nucleotide polymorphism in mucin 1, at chromosome 1q22,
      determines susceptibility to diffuse-type gastric cancer.
AB  - BACKGROUND & AIMS: Two major types of gastric cancer, intestinal and diffuse,
      develop through distinct mechanisms; the diffuse type is considered to be more
      influenced by genetic factors, although the mechanism is unknown. Our previous
      genome-wide association study associated 3 single nucleotide polymorphisms (SNPs)
      with diffuse-type gastric cancer (DGC); 1 was a functional SNP (rs2294008) in
      prostate stem cell antigen (PSCA), but the loci of the other 2 were not
      investigated. METHODS: We performed high-density mapping to explore a linkage
      disequilibrium status of the 2 SNPs at chromosome 1q22. A DGC case-control study
      was conducted using DNA from 606 cases and 1264 controls (all Japanese
      individuals) and validated using DNA from Japanese (304 cases, 1465 controls) and
      Korean (452 cases, 372 controls) individuals. The effects of SNPs on function
      were analyzed by reporter assays and analyses of splice variants. RESULTS: A
      region of a strong linkage disequilibrium with the 2 SNPs contained mucin 1
      (MUC1) and other 4 genes and SNPs significantly associated with DGC (rs2070803: P
      = 4.33 * 10(-13); odds ratio [OR], 1.71 by meta-analysis of the studies on the 3
      panels) but not with intestinal-type gastric cancer. Functional studies
      demonstrated that rs4072037 (P = 1.43 * 10(-11); OR, 1.66 by meta-analysis) in
      MUC1 affects promoter activity and determines the major splicing variants of MUC1
      in the gastric epithelium. Individuals that carry both SNPs rs2294008 in PSCA and
      rs4072037 in MUC1 have a high risk for developing DGC (OR, 8.38). CONCLUSIONS:
      MUC1 is the second major DGC susceptibility gene identified. The SNPs rs2070803
      and rs4072037 in MUC1 might be used to identify individuals at risk for this type
      of gastric cancer.

PMID- 21070780
TI  - Corticosterone mediates reciprocal changes in CB 1 and TRPV1 receptors in primary
      sensory neurons in the chronically stressed rat.
AB  - BACKGROUND & AIMS: Chronic stress is associated with visceral hyperalgesia in
      functional gastrointestinal disorders. We investigated whether corticosterone
      plays a role in chronic psychological stress-induced visceral hyperalgesia.
      METHODS: Male rats were subjected to 1-hour water avoidance (WA) stress or
      subcutaneous corticosterone injection daily for 10 consecutive days in the
      presence or absence of corticoid-receptor antagonist RU-486 and cannabinoid
      receptor agonist WIN55,212-2. The visceromotor response to colorectal distension
      was measured. Receptor protein levels were measured and whole-cell patch-clamp
      recordings were used to assess transient receptor potential vanilloid type 1
      (TRPV1) currents in L6-S2 dorsal root ganglion (DRG) neurons. Mass spectrometry
      was used to measure endocannabinoid anandamide content. RESULTS: Chronic WA
      stress was associated with visceral hyperalgesia in response to colorectal
      distension, increased stool output and reciprocal changes in cannabinoid receptor
      1 (CB1) (decreased) and TRPV1 (increased) receptor expression and function.
      Treatment of WA stressed rats with RU-486 prevented these changes. Control rats
      treated with serial injections of corticosterone in situ showed a significant
      increase in serum corticosterone associated with visceral hyperalgesia, enhanced
      anandamide content, increased TRPV1, and decreased CB1 receptor protein levels,
      which were prevented by co-treatment with RU-486. Exposure of isolated control L6
      S2 DRGs in vitro to corticosterone reproduced the changes in CB1 and TRPV1
      receptors observed in situ, which was prevented by co-treatment with RU-486 or
      WIN55,212-2. CONCLUSIONS: These results support a novel role for corticosterone
      to modulate CB1 and TRPV1-receptor pathways in L6-S2 DRGs in the chronic WA
      stressed rat, which contributes to visceral hyperalgesia observed in this model.

PMID- 21070782
TI  - Low cost antiviral activity of Plodia interpunctella haemolymph in vivo
      demonstrated by dose dependent infection.
AB  - Given the ubiquity of infectious disease it is important to understand the way in
      which hosts defend themselves and any costs that they may pay for this defence.
      Despite this, we know relatively little about insect immune responses to viruses
      when compared to their well-characterized responses to other pathogens. In
      particular it is unclear whether there is significant haemocoelic response to
      viral infection. Here we directly examine this question by examining whether
      there is a dose-dependency in infection risk when a DNA virus is injected
      directly into the haemocoel. Infection from direct injection into the haemocoel
      showed a clear dose dependency that is indicative of an active intrahaemocoelic
      immune response to DNA viruses in insects. In contrast to the natural oral
      infection route, we found no measurable sublethal effects in the survivors from
      direct injection. This suggests that the immune responses in the haemocoel are
      less costly than those that occur earlier.

PMID- 21070781
TI  - Budesonide 9 mg is at least as effective as mesalamine 4.5 g in patients with
      mildly to moderately active Crohn's disease.
AB  - BACKGROUND & AIMS: Comparative data on budesonide vs mesalamine for the treatment
      of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the
      efficacy and safety of each therapy in patients with mildly to moderately active
      CD. METHODS: We performed a randomized, double-blind, double-dummy, 8-week,
      multicenter study in which 309 patients with mildly to moderately active CD
      received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3
      times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day). RESULTS: The
      primary efficacy variable, clinical remission (defined as Crohn's Disease
      Activity Index <=150), at the final visit occurred in 69.5% (107 of 154) of
      patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine
      (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for
      noninferiority). Clinical remission rates did not differ significantly between
      the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity
      Index of 150 or less and/or a decrease of 70 or more (Delta70) or 100 or more
      (Delta100) points from baseline to final visit, did not differ significantly
      between patients given budesonide vs mesalamine (Delta70, P = .11; Delta100, P =
      .15), or between the 2 budesonide groups (Delta70, P = .38; Delta100, P = .78).
      No other efficacy end points differed significantly between groups.
      Discontinuation because of adverse events occurred in 3% and 5% of budesonide-
      and mesalamine-treated patients, respectively. There were no clinically relevant
      differences in adverse events between the 2 budesonide groups. CONCLUSIONS:
      Budesonide (9 mg/day) was numerically, but not statistically, more effective than
      Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately
      active CD. Budesonide (9 mg/day), administered once daily, was as effective as
      the standard (3 times daily) regimen.

PMID- 21070783
TI  - Adipokinetic hormones provide inference for the phylogeny of odonata.
AB  - Adipokinetic neuropeptides from the corpora cardiaca of 17 species of Odonata
      encompassing mainly the families Corduliidae and Libellulidae were isolated and
      structurally elucidated using liquid chromatography coupled with ion trap
      electrospray ionization mass spectrometry. It became evident that all species of
      the family Corduliidae studied express the peptide code-named Libau-AKH (pGlu-Val
      Asn-Phe-Thr-Pro-Ser-Trp amide), which is also present in all but one libellulid
      species, Erythemis simplicicollis which expresses Erysi-AKH (pGlu-Leu-Asn-Phe-Thr
      Pro-Ser-Trp amide). This divergence from all other Libellulids is due to a
      nonsynonymous missense single nucleotide polymorphism (SNP) in the nucleotide
      coding sequence (CDS) of prepro-AKH CDS and supports the polyphyletic nature of
      Sympetrinae and other subfamilies of libellulids. Despite this exception, these
      findings then support the hypothesis that Corduliidae and Libellulidae are
      closely related as stated in most phylogenies. The presence of Anaim-AKH (pGlu
      Val-Asn-Phe-Ser-Pro-Ser-Trp amide) in Macromiidae likely distinguishes species in
      this family from Corduliidae. Current molecular genetic phylogenies and our AKH
      findings suggest that Syncordulia gracilis, which expresses Anaim-AKH, does not
      belong in Corduliidae. Evolution of AKHs in anisopteran Odonata are likely due to
      nucleotide substitution involving nonsynonymous missense SNPs in the CDS of
      prepro-AKH.

PMID- 21070784
TI  - The overwintering physiology of the emerald ash borer, Agrilus planipennis
      fairmaire (coleoptera: buprestidae).
AB  - Ability to survive cold is an important factor in determining northern range
      limits of insects. The emerald ash borer (Agrilus planipennis) is an invasive
      beetle introduced from Asia that is causing extensive damage to ash trees in
      North America, but little is known about its cold tolerance. Herein, the cold
      tolerance strategy and mechanisms involved in the cold tolerance of the emerald
      ash borer were investigated, and seasonal changes in these mechanisms monitored.
      The majority of emerald ash borers survive winter as freeze-intolerant prepupae.
      In winter, A. planipennis prepupae have low supercooling points (approximately 
      30 degrees C), which they achieve by accumulating high concentrations of glycerol
      (approximately 4M) in their body fluids and by the synthesis of antifreeze
      agents. Cuticular waxes reduce inoculation from external ice. This is the first
      comprehensive study of seasonal changes in cold tolerance in a buprestid beetle.

PMID- 21070785
TI  - Tangible benefits of the aphid Acyrthosiphon pisum genome sequencing for aphid
      proteomics: Enhancements in protein identification and data validation for
      homology-based proteomics.
AB  - Homology-driven proteomics promises to reveal functional biology in insects with
      sparse genome sequence information. A proteomics study comparing plant virus
      transmission competent and refractive genotypes of the aphid Schizaphis graminum
      isolated numerous candidate proteins involved in virus transmission, but limited
      genome sequence information hampered their identification. The complete genome of
      the pea aphid, Acyrthosiphon pisum, released in 2008, enabled us to double the
      number of protein identifications beyond what was possible using available EST
      libraries and other insect sequences. This was concomitant with a dramatic
      increase of the number of MS and MS/MS peptide spectra matching the genome
      derived protein sequence. LC-MS/MS proved to be the most robust method of peptide
      detection. Cross-matching spectral data to multiple EST sequences and error
      tolerant searching to identify amino acid substitutions enhanced the percent
      coverage of the Schizaphis graminum proteins. 2-D electrophoresis provided the
      protein pI and MW which enabled the refinement of the candidate protein selection
      and provided a measure of protein abundance when coupled to the spectral data.
      Thus, the homology-based proteomics pipeline for insects should include efforts
      to maximize the number of peptide matches to the protein to increase certainty in
      protein identification and relative protein abundance.

PMID- 21070786
TI  - A mathematical model of the intracellular replication and within host evolution
      of hepatitis type B virus: Understanding the long time course of chronic
      hepatitis.
AB  - Hepatitis B virus (HBV) causes acute and chronic liver disease. Especially,
      chronic hepatitis is a major risk factor of liver cirrhosis and hepatocellular
      carcinoma. Viral kinetics of HBV observed in peripheral blood is quite different
      depending on the clinical course of hepatitis. But the relationship between the
      intracellular replication dynamics and clinical course of HBV infection is
      unclear. Further it is very difficult to predict the long time course of
      hepatitis because the nature of HBV is changed by mutation within host with high
      mutation rate. We investigate the intracellular replication dynamics and within
      host evolution of HBV by using a mathematical model. Two different intracellular
      replication patterns of HBV, "explosive" and "arrested", are switched depending
      on the viral gene expression pattern. In the explosive replication, prominent
      growth of HBV is observed. On the other hand, the virion production is restricted
      in the arrested replication. It is suggested that the arrested and explosive
      replication is associated with chronic hepatitis and exacerbation of hepatitis
      respectively. It is shown by our evolutionary simulation that the exacerbation of
      hepatitis is caused by the emergence of explosive genotype of HBV from arrested
      genotype by mutation during chronic hepatitis. It is also shown that chronic
      infection without exacerbation is maintained by short waiting time for virion
      release and superinfection with arrested genotype. It is suggested that extension
      of waiting time for virion release and existence of uninfected hepatocyte in the
      liver may become risk factors for the exacerbation of hepatitis.

PMID- 21070787
TI  - AMP-activated protein kinase regulates the expression of monocarboxylate
      transporter 4 in skeletal muscle.
AB  - AIMS: The aim of this study was to determine the effect of 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR), an AMP-activated protein kinase
      (AMPK) activator, on monocarboxylate transporter 4 (MCT4) expression in rat
      skeletal muscle and a prototypic embryonal rhabdomyosarcoma cell line (RD cells).
      MAIN METHODS: We examined the alteration in Glucose transporter 4 (GLUT4) and
      MCT4 mRNA levels by quantitative real-time PCR. Alteration in GLUT4 and MCT4
      protein levels was examined by Western blotting. KEY FINDINGS: In an in vivo
      study, AICAR increased MCT4 mRNA and protein levels in a fiber-type specific
      manner. In an in vitro study, AICAR increased MCT4 mRNA and protein levels.
      Moreover, AICAR-induced MCT4 expression was blocked by Compound C, an AMPK
      inhibitor. SIGNIFICANCE: In this study, we found that AMPK activation induced
      expression of MCT4 in RD cells and rat skeletal muscle in a fiber-type specific
      manner. These results indicate the possible involvement of an AMPK-mediated
      pathway associated with MCT4 expression in skeletal muscle.

PMID- 21070788
TI  - Development of a variational scheme for model inversion of multi-area model of
      brain. Part I: simulation evaluation.
AB  - We previously developed an integrated model of the brain within a single cortical
      area for functional Magnetic Resonance Imaging (fMRI), electroencephalography
      (EEG), and magnetoencephalography (MEG) using an extended neural mass model
      (ENMM). We then extended ENMM from a single-area to a multi-area model to develop
      a neural mass model of the entire brain. To this end, we derived a nonlinear
      state-space representation of the multi-area model. In Parts I and II of these
      two companion papers (henceforth called Part I and Part II), we develop and
      evaluate a variational Bayesian expectation maximization (VBEM) method to
      estimate parameters of multi-area ENMM (MEN) using E/MEG data. In Part I, we
      derive a state-space representation of MEN and use VBEM method for model
      inversion (parameter estimation). We evaluate and validate performance of VBEM
      method for model inversion of MEN using simulation studies in various signal-to
      noise ratios. Details of VBEM method are presented in Part II. The proposed
      approach provides a useful technique for analyzing effective connectivity using
      non-invasive EEG and MEG methods.

PMID- 21070789
TI  - The chikungunya disease: modeling, vector and transmission global dynamics.
AB  - Models for the transmission of the chikungunya virus to human population are
      discussed. The chikungunya virus is an alpha arbovirus, first identified in 1953.
      It is transmitted by Aedes mosquitoes and is responsible for a little documented
      uncommon acute tropical disease. Models describing the mosquito population
      dynamics and the virus transmission to the human population are discussed. Global
      analysis of equilibria are given, which use on the one hand Lyapunov functions
      and on the other hand results of the theory of competitive systems and stability
      of periodic orbits.

PMID- 21070790
TI  - Behavioral responses of Poecilia vivipara (Osteichthyies: Cyprinodontiformes) to
      experimental infections of Acanthocollaritrema umbilicatum (Digenea:
      Cryptogonimidae).
AB  - The swimming behavior of Poecilia vivipara was evaluated using an image analysis
      system comparing laboratory-reared uninfected fish before and after experimental
      infection with different intensities of cercariae of the trematode
      Acanthocollaritrema umbilicatum. Two experiments were performed, each with 30
      fish which were individually exposed to 30 and 50 cercariae, respectively, shed
      from experimentally infected molluscs, Heleobia australis. Before and after (17
      27 days) infection, the behavior of each fish was monitored in terms of Distance
      travelled, Ambulatory time, Stereotypic time, Resting time and Average speed. At
      the end of the experiments, the fish were dissected to count the number of
      metacercariae recovered. In the experiment with 30 cercariae, fish with 2-10
      metacercariae did not exhibit any significant differences in their swimming
      activity, but those with 11-22 metacercariae had a significantly enhanced
      Stereotypic time and a reduced Time Resting. In the experiment with 50 cercariae,
      fish with 5-22 metacercariae had an enhanced Distance travelled and a reduced
      Average speed; highly significant differences occurred with regard to all
      behavioral parameters when considering the subgroup 23-36 metacercariae: Distance
      travelled, Stereotypic time, Resting time, Ambulatory time and Average speed. The
      swimming behavior of P. vivipara changed influenced by an intensity-dependence on
      metacercariae of A. umbilicatum, supporting the prediction that parasites are
      able to alter the behavior of their hosts.

PMID- 21070791
TI  - Transdermal iontophoresis as an in-vivo technique for studying microvascular
      physiology.
AB  - Assessment of microvascular function is of major importance in understanding the
      physiology of the vasculature and in investigating the vascular effects of
      pathological conditions. Transdermal iontophoresis can be used to non-invasively
      introduce vasoactive drugs into the skin. The response of the local cutaneous
      microvasculature to these drugs can be measured by methods such as laser Doppler
      flowmetry. Although the technique has been used for over two decades, there are
      still important methodological issues to be resolved. This review describes the
      technique of iontophoresis as well as its development during recent years, while
      focusing on how iontophoresis can be used as an in-vivo model for studying
      physiologic mechanisms and on the analysis and interpretation of dose-response
      data.

PMID- 21070792
TI  - RNA interference against transcription elongation factor SII does not support its
      role in transcription-coupled nucleotide excision repair.
AB  - RNA polymerase II is unable to bypass bulky DNA lesions induced by agents like
      ultraviolet light (UV light) and cisplatin that are located in the template
      strand of active genes. Arrested polymerases form a stable ternary complex at the
      site of DNA damage that is thought to pose an impediment to the repair of these
      lesions. Transcription-coupled nucleotide excision repair (TC-NER) preferentially
      repairs these DNA lesions through an incompletely defined mechanism. Based on
      elegant in vitro experiments, it was hypothesized that the transcription
      elongation factor IIS (TFIIS) may be required to couple transcription to repair
      by catalyzing the reverse translocation of the arrested polymerase, allowing
      access of repair proteins to the site of DNA damage. However the role of TFIIS in
      this repair process has not been tested in vivo. Here, silencing TFIIS using an
      RNA interference strategy did not affect the ability of cells to recover nascent
      RNA synthesis following UV exposure or the ability of cells to repair a UV
      damaged reporter gene while a similar strategy to decrease the expression
      Cockayne syndrome group B protein (CSB) resulted in the expected repair defect.
      Furthermore, RNA interference against TFIIS did not increase the sensitivity of
      cells to UV light or cisplatin while decreased expression of CSB did. Taken
      together, these results indicate that TFIIS is not limiting for the repair of
      transcription-blocking DNA lesions and thus the present work does not support a
      role for TFIIS in TC-NER.

PMID- 21070793
TI  - The nature of auditory discrimination problems in children with specific language
      impairment: an MMN study.
AB  - Many children with specific language impairment (SLI) show impairments in
      discriminating auditorily presented stimuli. The present study investigates
      whether these discrimination problems are speech specific or of a general
      auditory nature. This was studied using a linguistic and nonlinguistic contrast
      that were matched for acoustic complexity in an active behavioral task and a
      passive ERP paradigm, known to elicit the mismatch negativity (MMN). In addition,
      attention skills and a variety of language skills were measured. Participants
      were 25 five-year-old Dutch children with SLI having receptive as well as
      productive language problems and 25 control children with typical speech- and
      language development. At the behavioral level, the SLI group was impaired in
      discriminating the linguistic contrast as compared to the control group, while
      both groups were unable to distinguish the non-linguistic contrast. Moreover, the
      SLI group tended to have impaired attention skills which correlated with
      performance on most of the language tests. At the neural level, the SLI group, in
      contrast to the control group, did not show an MMN in response to either the
      linguistic or nonlinguistic contrast. The MMN data are consistent with an account
      that relates the symptoms in children with SLI to non-speech processing
      difficulties.

PMID- 21070795
TI  - Synthesis and characterisation of new types of side chain cholesteryl polymers.
AB  - A series of cholesterol derivatives have been synthesised via the alkylation
      reaction of the 3-hydroxyl group with the aliphatic bromide compounds with
      different chain lengths, namely 3beta-alkyloxy-cholesterol. The double bond
      between the C5 and C6 positions in these cholesterol derivatives was oxidised
      into epoxy, followed by an epoxy-ring-opening reaction with the treatment with
      acrylic acid, resulting in a series of 3beta-alkyloxy-5alpha-hydroxy-6beta
      acryloyloxycholesterol, C(n)OCh (n=1, 2, 4, 6, 8, 10, 12), The acrylate group is
      connected to the C6 position, which is confirmed by the single crystal structure
      analysis. The corresponding polymers, PC(n)OCh, were prepared via free radical
      polymerisation. The structure of monomers and the resulting polymers were
      characterised with nuclear magnetic resonance (NMR), Fourier transform infrared
      spectroscopy (FT-IR) and gel permeation chromatography (GPC). The thermal
      properties of PC(n)OCh were studied using differential scanning calorimetry (DSC)
      and thermogravimetric analysis (TGA). To determine the secondary structure of
      polymers, circular dichroism (CD) spectra were performed. It was found that not
      all monomers produce high-molecular-weight polymers because of steric hindrance.
      However, all polymers have a helical structure, which can be enhanced by
      increasing the alkoxy chain length. In addition, increasing the alkoxy chain
      length decreases the glass transition temperature and increases the decomposition
      temperature of the polymers.

PMID- 21070794
TI  - Synthesis and photochemical transformation of 3beta,21-dihydroxypregna-5,7-dien
      20-one to novel secosteroids that show anti-melanoma activity.
AB  - We have synthesized 3beta,21-dihydroxypregna-5,7-dien-20-one (21(OH) 7DHP) and
      used UVB radiation to induce its photoconversion to analogues of vitamin D (pD),
      lumisterol (pL) and tachysterol (pT). The number and character of the products
      and the dynamics of the process were dependent on the UVB dose. The main
      products: pD and pT compounds were characterized by UV absorption, MS and NMR
      spectroscopy after RP-HPLC chromatography. In addition, formation of multiple
      oxidized derivatives of the primary products was detected and one of these
      derivatives was characterized as oxidized 21-hydroxyisotachysterol compound
      (21(OH)oxy-piT). These newly synthesized compounds inhibited growth of human
      melanoma cells in a dose dependent manner, with greater or equal potency to
      calcitriol. 3beta,21-Dihydroxy-9beta,10alpha-pregna-5,7-dien-20-one (21(OH)pL)
      and 21(OH)oxy-piT had higher potency against pigmented melanoma cells, while the
      EC(50) for compounds 21(OH)7DHP and (5Z,7E)-3beta,21-dihydroxy-9,10-secopregna
      5,7,10(19)-trien-20-one (21(OH)pD) were similar in both pigmented and non
      pigmented cells. Moreover, 21(OH)7DHP and its derivatives inhibited proliferation
      of human epidermal HaCaT keratinocytes, albeit at a lower activity compared to
      melanoma cells. Importantly, 21(OH)7DHP derivatives strongly inhibited the colony
      formation of human melanoma cells with 21(OH)pD being the most potent. The
      potential mechanism of action of newly synthesized compounds was similar to that
      mediated by 1,25(OH)(2)D(3) and involved ligand-induced translocation of vitamin
      D receptor into the nucleus. In summary, we have characterized for the first time
      products of UVB-induced conversion of 21(OH)7DHP and documented that these
      compounds have selective, inhibitory effects on melanoma cells.

PMID- 21070796
TI  - Reexamination of testosterone, dihydrotestosterone, estradiol and estrone levels
      across the menstrual cycle and in postmenopausal women measured by liquid
      chromatography-tandem mass spectrometry.
AB  - Measuring serum androgen levels in women has been challenging due to limitations
      in method accuracy, precision sensitivity and specificity at low hormone levels.
      The clinical significance of changes in sex steroids across the menstrual cycle
      and lifespan has remained controversial, in part due to these limitations. We
      used validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays
      to determine testosterone (T) and dihydrotestosterone (DHT) along with estradiol
      (E2) and estrone (E1) levels across the menstrual cycle of 31 healthy
      premenopausal females and in 19 postmenopausal females. Samples were obtained in
      ovulatory women in the early follicular phase (EFP), midcycle and mid luteal
      phase (MLP). Overall, the levels of T, DHT, E2 and E1 in premenopausal women
      measured by LC-MS/MS were lower overall than previously reported with
      immunoassays. In premenopausal women, serum T, free T, E2, E1 and SHBG levels
      peaked at midcycle and remained higher in the MLP, whereas DHT did not change. In
      postmenopausal women, T, free T, SHBG and DHT were significantly lower than in
      premenopausal women, concomitant with declines in E2 and E1. These data support
      the hypothesis that the changes in T and DHT that occur across the cycle may
      reflect changes in SHBG and estrogen, whereas in menopause, androgen levels
      decrease. LC-MS/MS may provide more accurate and precise measurement of sex
      steroid hormones than prior immunoassay methods and can be useful to assess the
      clinical significance of changes in T, DHT, E2 and E1 levels in females.

PMID- 21070797
TI  - Heavy resistance exercise training and skeletal muscle androgen receptor
      expression in younger and older men.
AB  - Effects of heavy resistance exercise on serum testosterone and skeletal muscle
      androgen receptor (AR) concentrations were examined before and after a 21-week
      resistance training period. Seven healthy untrained young adult men (YT) and ten
      controls (YC) as well as ten older men (OT) and eight controls (OC) volunteered
      as subjects. Heavy resistance exercise bouts (5 * 10 RM leg presses) were
      performed before and after the training period. Muscle biopsies were obtained
      before and 1h and 48 h after the resistance exercise bouts from m.vastus
      lateralis (VL) to determine cross-sectional area of muscle fibers (fCSA) and AR
      mRNA expression and protein concentrations. No changes were observed in YC and OC
      while resistance training led to significant increases in maximal strength of leg
      extensors (1 RM), fCSA and lean body mass in YT and OT. Acute increases occurred
      in serum testosterone concentrations due to resistance exercises but basal
      testosterone remained unaltered. Mean AR mRNA expression and protein
      concentration remained unchanged after heavy resistance exercise bouts compared
      to pre-values. The individual pre- to post-training changes in resting (pre
      exercise) AR protein concentration correlated with the changes in fCSA and lean
      body mass in the combined group of YT and OT. Similarly, it correlated with the
      changes in 1 RM in YT. Although mean AR expression did not changed due to the
      resistance exercise training, the present findings suggest that the individual
      changes of AR protein concentration in skeletal muscle following resistance
      training may have an impact on training-induced muscular adaptations in both
      younger and older men.

PMID- 21070799
TI  - Tissue factor contributes to neutrophil CD11b expression in alpha
      naphthylisothiocyanate-treated mice.
AB  - Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is
      provoked by injury to intrahepatic bile ducts and the progression of hepatic
      necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic
      cells including neutrophils. Recent studies have shown that myeloid cell TF
      contributes to neutrophil activation. We tested the hypothesis that myeloid cell
      TF contributes to neutrophil activation in ANIT-treated mice. TF activity in
      liver homogenates increased significantly in TF(flox/flox) mice treated with
      ANIT, but not in TF(flox/flox)/LysMCre mice (TF(DeltaMyeloid) mice), which have
      reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell
      specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but
      reduced hepatic neutrophil accumulation in ANIT-treated mice at 48 h as indicated
      by tissue myeloperoxidase (MPO) activity. Myeloid cell TF deficiency
      significantly reduced CD11b expression by blood neutrophils in ANIT-treated mice,
      and this was associated with reduced plasma MPO protein levels, an index of
      neutrophil degranulation. However, myeloid cell-specific TF deficiency had no
      effect on ANIT-induced coagulation cascade activation. The increase in serum ALT
      and ALP activities in ANIT-treated mice was reduced by myeloid cell TF deficiency
      (p<0.05), but the myeloid cell TF deficiency did not reduce hepatic necrosis at
      48 h, as determined by histopathology and morphometry. The results suggest that
      myeloid cell TF contributes to neutrophil CD11b expression during cholestasis by
      a coagulation-independent pathway. However, the resultant reduction in neutrophil
      accumulation/activation is insufficient to substantially reduce ANIT
      hepatotoxicity, suggesting that myeloid cell TF is only one of many factors
      modulating hepatic necrosis during cholestasis.

PMID- 21070798
TI  - Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced
      cell proliferation in rat spleen.
AB  - Aniline exposure is associated with toxicity to the spleen leading to
      splenomegaly, hyperplasia, fibrosis and a variety of sarcomas of the spleen on
      chronic exposure. In earlier studies, we have shown that aniline exposure leads
      to iron overload, oxidative stress and activation of redox-sensitive
      transcription factors, which could regulate various genes leading to a
      tumorigenic response in the spleen. However, molecular mechanisms leading to
      aniline-induced cellular proliferation in the spleen remain largely unknown. This
      study was, therefore, undertaken on the regulation of G1 phase cell cycle
      proteins (cyclins), expression of cyclin-dependent kinases (CDKs),
      phosphorylation of retinoblastoma protein (pRB) and cell proliferation in the
      spleen, in an experimental condition preceding a tumorigenic response. Male SD
      rats were treated with aniline (0.5 mmol/kg/day via drinking water) for 30 days
      (controls received drinking water only), and splenocyte proliferation, protein
      expression of G1 phase cyclins, CDKs and pRB were measured. Aniline treatment
      resulted in significant increases in splenocyte proliferation, based on cell
      counts, cell proliferation markers including proliferating cell nuclear antigen
      (PCNA), nuclear Ki67 protein (Ki67) and minichromosome maintenance (MCM), MTT
      assay and flow cytometric analysis. Western blot analysis of splenocyte proteins
      from aniline-treated rats showed significantly increased expression of cyclins
      D1, D2, D3 and E, as compared to the controls. Similarly, real-time PCR analysis
      showed significantly increased mRNA expression for cyclins D1, D2, D3 and E in
      the spleens of aniline-treated rats. The overexpression of these cyclins was
      associated with increases in the expression of CDK4, CDK6, CDK2 as well as
      phosphorylation of pRB protein. Our data suggest that increased expression of
      cyclins, CDKs and phosphorylation of pRB protein could be critical in cell
      proliferation, and may contribute to aniline-induced tumorigenic response in the
      spleen.

PMID- 21070800
TI  - Role of TNFR1 in lung injury and altered lung function induced by the model
      sulfur mustard vesicant, 2-chloroethyl ethyl sulfide.
AB  - Lung toxicity induced by sulfur mustard is associated with inflammation and
      oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2
      chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice
      (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals
      were sacrificed 3, 7 or 14 days later and bronchoalveolar lavage (BAL) fluid and
      lung tissue collected. Treatment of mice with CEES resulted in an increase in BAL
      protein, an indication of alveolar epithelial damage, within 3 days. Expression
      of Ym1, an oxidative stress marker also increased in the lung, along with
      inducible nitric oxide synthase, and at 14 days, cyclooxygenase-2 and monocyte
      chemotactic protein-1, inflammatory proteins implicated in tissue injury. These
      responses were attenuated in mice lacking the p55 receptor for TNFalpha (TNFR1-/
      ), demonstrating that signaling via TNFR1 is key to CEES-induced injury,
      oxidative stress, and inflammation. CEES-induced upregulation of CuZn-superoxide
      dismutase (SOD) and MnSOD was delayed or absent in TNFR1-/- mice, relative to WT
      mice, suggesting that TNFalpha mediates early antioxidant responses to lung
      toxicants. Treatment of WT mice with CEES also resulted in functional alterations
      in the lung including decreases in compliance and increases in elastance.
      Additionally, methacholine-induced alterations in total lung resistance and
      central airway resistance were dampened by CEES. Loss of TNFR1 resulted in
      blunted functional responses to CEES. These effects were most notable in the
      airways. These data suggest that targeting TNFalpha signaling may be useful in
      mitigating lung injury, inflammation and functional alterations induced by
      vesicants.

PMID- 21070801
TI  - Modulation of protein kinase signaling cascades by palytoxin.
AB  - Although known for its acutely toxic action, palytoxin has also been identified
      as a type of carcinogenic agent called a tumor promoter. In general tumor
      promoters do not damage DNA, but instead contribute to carcinogenesis by
      disrupting the regulation of cellular signaling. The identification of palytoxin
      as a tumor promoter, together with the recognition that the Na(+), K(+)-ATPase is
      its receptor, led to research on how palytoxin triggers the modulation of signal
      transduction pathways. This review focuses on mitogen activated protein (MAP)
      kinases as mediators of palytoxin-stimulated signaling. MAP kinases are a family
      of serine/threonine kinases that relay a variety of signals to the cellular
      machinery that regulates cell fate and function. The studies discussed in this
      review investigated how palytoxin stimulates MAP kinase activity and, in turn,
      how MAP kinases mediate the response of cells to palytoxin.

PMID- 21070802
TI  - LC-MS of palytoxin and its analogues: State of the art and future perspectives.
AB  - The state of the art of LC-MS of palytoxin and its analogues is reported in the
      present review. MS data for palytoxin, 42-hydroxy-palytoxin, ostreocin-D,
      mascarenotoxins, and ovatoxins, obtained using different ionization techniques,
      namely fast-atom bombardment (FAB), matrix assisted laser desorption ionization
      (MALDI), and electrospray ionization (ESI), are summarized together with the LC
      MS methods used for their detection. Application of the developed LC-MS methods
      to both plankton and seafood analysis is also reported, paying attention to the
      extraction procedures used and to limits of detection (LOD) and quantitation
      (LOQ) achieved. In a research setting, LC-MS has shown a good potential in
      determination of palytoxin and its analogues from various sources, but, in a
      regulatory setting, routine LC-MS analysis of palytoxins is still at a
      preliminary stage. The LOQ currently achieved in seafood analysis appears
      insufficient to detect palytoxins in shellfish extract at levels close to the
      tolerance limit for palytoxins (30 MUg/kg) proposed by the European Food Safety
      Authority (EFSA, 2009). In addition, lacking of certified reference standard of
      palytoxins as well as of validation studies for the proposed LC-MS methods
      represent important issues that should be faced for future perspectives of LC-MS
      technique.

PMID- 21070803
TI  - Inositol and its derivatives: their evolution and functions.
AB  - Ins and Ins phospholipids are present in and are made by most Archaea and all
      eukaryotes. Relatively few bacteria possess Ins phospholipids: and only one major
      grouping, the Actinobacteria, is known to have evolved multiple functions for Ins
      derivatives. The Ins phospholipids of all organisms, whether they have
      diradylglycerol or ceramide backbones, seem to use the same Ins1P headgroup
      stereochemistry, so they are probably made by evolutionarily conserved pathways.
      It seems likely that an early member of the Archaea made the first phospholipid
      with an Ins1P headgroup -maybe three billionyears ago - and that amuchlater
      archaeal descendentwas the ancestral contributor that brought these molecules
      into the common ancestor of all eukaryotes - maybe two billionyears ago (Michell,
      2007, 2008). It will only be possible to infer the likely details of these
      processes when we have learned much more about the Ins lipid biochemistry of
      modern archaeons. All eukaryotes make substantial amounts of PtdIns, both as a
      'bulk' membrane phospholipid and as the precursor of seven phosphorylated
      derivatives of PtdIns (the polyphosphoinositides; PPIn) and of the 'GPI anchors'
      of cell surface ectoproteins. PtdIns(4,5)P2 - with its many functions - and its
      precursor PtdIns4P are found in all in eukaryotes. So are PtdIns3P and
      PtdIns(3,5)P2, which have ubiquitous roles in the regulation of membrane
      trafficking events. However, synthesis of and signalling by PtdIns(3,4,5) P 3
      appears to be confined to a later-evolved group of eukaryotes.

PMID- 21070804
TI  - Type 2 diabetes in Indigenous populations: quality of intervention research over
      20 years.
AB  - BACKGROUND: A robust evidence base is needed to reduce the disproportionately
      high rates of diabetes-related mortality and complications among Indigenous
      peoples. OBJECTIVE: This study aimed to evaluate the quantity and methodological
      quality of published intervention research on Type 2 and gestational diabetes in
      the Indigenous populations of Australia, Canada, New Zealand, and the United
      States from 1989 to 2008. A robust evidence base is needed to reduce the
      disproportionately high rates of diabetes-related mortality and complications
      among Indigenous peoples. METHODS: Systematic searches of Medline, Embase, and
      EBM Reviews identified publications focused on Type 2 or gestational diabetes in
      Indigenous peoples published between 1 January 1989 and 31 December 2008. Total
      publication number and proportion of research involving interventions over time
      were examined. The quality of intervention studies was evaluated using Cochrane's
      Effective Practice and Organisation of Care (EPOC) criteria. RESULTS: Total
      publication number increased significantly over the 20 years (p<0.004). Research
      was predominantly descriptive (87%), with the proportion of research involving
      interventions increasing from 3% in 1989-1993 to 12% in 2003-2008 (chi(2)=12.42,
      df=3, p=0.006). However, only 25% (95%CI: 9-41%) of intervention studies met the
      EPOC methodological quality criteria; other studies lacked sufficient controls or
      measurements over time. CONCLUSIONS: Increases in the amount of high-quality
      intervention research for prevention and treatment of Type 2 and gestational
      diabetes among Indigenous populations of these countries are needed.

PMID- 21070805
TI  - Parenting styles, parenting practices, and physical activity in 10- to 11-year
      olds.
AB  - OBJECTIVE: The objective of this study was to determine whether parenting styles
      and practices are associated with children's physical activity. METHODS: Cross
      sectional survey of seven hundred ninety-two 10- to 11-year-old UK children in
      Bristol (UK) in 2008-2009 was conducted. Accelerometer-assessed physical activity
      and mean minutes of moderate-to-vigorous physical activity (mean MVPA) and mean
      counts per minute (mean CPM) were obtained. Maternal parenting style and physical
      activity parenting practices were self-reported. RESULTS: In regression analyses,
      permissive parenting was associated with higher mean MVPA among girls (+6.0
      min/day, p<0.001) and greater mean CPM (+98.9 accelerometer counts/min, p=0.014)
      among boys when compared to children with authoritative parents. Maternal
      logistic support was associated with mean CPM for girls (+36.2 counts/min,
      p=0.001), while paternal logistic support was associated with boys' mean MVPA
      (+4.0 min/day, p=0.049) and mean CPM (+55.7 counts/min, p=0.014). CONCLUSIONS:
      Maternal permissive parenting was associated with higher levels of physical
      activity than authoritative parenting, but associations differed by child gender
      and type of physical activity. Maternal logistic support was associated with
      girls' physical activity, while paternal logistic support was associated with
      boys' physical activity. Health professionals could encourage parents to increase
      logistic support for their children's physical activity.

PMID- 21070806
TI  - The Alberta Physical Activity and Breast Cancer Prevention Trial: quality of life
      outcomes.
AB  - OBJECTIVE: Interventions for disease prevention should also be evaluated for
      quality of life (QoL) effects. Few exercise trials have examined QoL in the
      context of primary disease prevention. Here, we report the QoL outcomes from the
      Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial. METHODS:
      The ALPHA trial was a randomized controlled trial in Calgary and Edmonton, Canada
      between May 2003 and July 2007 that compared an exercise intervention to a
      sedentary lifestyle among 320 sedentary, postmenopausal women. The exercise group
      was asked to perform moderate-to-vigorous intensity aerobic exercise 45 min/day,
      5 days/week for 1 year. QoL was assessed by the short form-36 health survey.
      RESULTS: Compared to the control group, the exercise group maintained
      significantly better physical functioning (p<0.001), general health (p<0.001),
      vitality (p=0.002), and bodily pain (p=0.020) by 4-5 points which exceeds the 3.0
      minimally important difference for these scales. Changes in body composition
      partially mediated the intervention effects. Antidepressant use and the presence
      of comorbidities moderated some intervention effects. CONCLUSIONS: A 1-year
      moderate-to-vigorous aerobic exercise program prevents declines in the physical
      aspects of QoL in postmenopausal women. Exercise may have a potentially important
      advantage for breast cancer prevention compared to other lifestyle or biomedical
      interventions.

PMID- 21070807
TI  - Some biomolecules and a partially O-acetylated exo-galactomannan containing beta
      Galf units from pathogenic Exophiala jeanselmei, having a pronounced immunogenic
      response.
AB  - The pathogenic fungus Exophiala jeanselmei (Ej4) was grown in submerged MM
      medium, glucose being consumed after six days with maximum biomass and EPS
      production. Cells were extracted with CHCl3-MeOH (2:1, v/v) yielding a product
      containing 10% lipid, with high levels of unsaturated C(18:1) (43.6%) and C(18:2)
      (21.0%), 2D-TLC showed the presence of PE (17.7%), PS (11.6%), PC (35.8%), PI
      (1.2%) and lyso-phospholipids, LPE (10.7%), LPC (2.0%), PA (10.4%), cardiolipin
      (10.5%) and glucosyl-ceramide. Analysis of EPS-1 (120 kDa) showed a galactomanan,
      containing a main chain of Manp-(1->2) (24.2%), substituted by side chains
      containing terminal Galf (16.8%) and Manp (3.5%) and acetyl groups attached at O
      6 of terminal Galf. An immune response against antigens was obtained using Balb/C
      mice. Anti-EPS-1 antibodies recognized purified fraction containing cellular
      walls very titer and higher than 1:20,000 for EPS. The studied biomolecules
      showed biotechnological potential and point to important perspectives in
      diagnosis of fungi and immunomodulatory products.

PMID- 21070808
TI  - The socio-emotional processing stream in Anorexia Nervosa.
AB  - The significance of socio-emotional factors in development and maintenance of
      Anorexia Nervosa (AN) has been noted, but the literature is poorly integrated
      without clear models guiding research or treatment. This systematic review
      retrieved experimental studies of social-cognitive or affective processing in AN
      and categorised them using Ochsner's "Social-Emotional Processing Stream."
      Ochsner's "Processing Stream", based on healthy data, comprises five constructs:
      (1) acquisition of and (2) recognition and response to social-affective stimuli,
      (3) low-level and (4) high-level mental state inference and (5) context-sensitive
      emotion regulation. Thirty-seven experimental studies in Anorexia Nervosa were
      identified, mapping on to four of the five constructs (not Construct 3). A meta
      analysis of nine affect recognition studies was conducted. AN patients
      demonstrated impairments in each of the four domains with preliminary reports
      that some difficulties are trait-like, and others ameliorate following recovery.
      Socio-emotional data was integrated with previous reports of neural abnormalities
      to generate an AN specific model of socio-emotional processing. Additional
      research is required for further definition and to translate experimental
      findings into clinical practice.

PMID- 21070809
TI  - Quantitative real-time PCR for rhinovirus, and its use in determining the
      relationship between TCID50 and the number of viral particles.
AB  - The development of a quantitative real-time PCR (qPCR) assay for human rhinovirus
      serotype 16 (HRV16) is described using the plasmid pR16.11, which contains the
      full-length genome of HRV16. A standard curve was generated by plotting the
      critical threshold (C(t)) against numbers of plasmid. The limit of sensitivity
      was less than10 cDNA copies, and the curve showed a high degree of linearity over
      a range of 10(1) to 10(6) cDNA copies with r(2)>=0.9989. Amplification efficiency
      of the qPCR was greater than 97.6 percent. The standard curve was highly
      reproducible with low intra- and inter-assay coefficients of variation. Standard
      curves were also generated from cDNA derived from two viral suspensions of known
      TCID(50), and were exactly parallel to those generated from the plasmid.
      Comparison of the curves generated from the plasmid or viral cDNA showed that for
      the two suspensions, TCID(50) corresponded to either 142 or 2088 viral particles.
      This new qPCR will permit quantitative assessments of interactions between virus
      and epithelium such as determinations of the affinity and number of viral binding
      sites or of the number of virus produced per infected cell.

PMID- 21070810
TI  - Cellular IMPDH enzyme activity is a potential target for the inhibition of
      Chikungunya virus replication and virus induced apoptosis in cultured mammalian
      cells.
AB  - Inosine monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de
      novo biosynthesis of guanine nucleotide, namely, the conversion of IMP to XMP.
      The depletion of the intracellular GTP and dGTP pools is the major event
      occurring in the cells exposed to the inhibitors such as mycophenolic acid. The
      present study was undertaken with an objective to assess the antiviral potential
      of mycophenolic acid (MPA) against Chikungunya virus via inhibition of IMPDH
      enzyme in Vero cells. The inhibitory potential of MPA on CHIKV replication was
      assessed by virus inhibition assay (cytopathic effect, immunofluorescence), virus
      yield reduction assay and cell viability assay. Inhibition of virus induced
      apoptosis was analyzed by Hoechst staining, DNA fragmentation, immunoblotting of
      Caspase-3, PARP and Bcl-2. Percentage apoptotic cell population was determined by
      flow cytometry. Total genome infectivity was determined by analyzing the ratio of
      total infectious viral particles to the genome copy number. Non-toxic
      concentration of MPA (10 MUM) reduced >= 99.9% CHIKV titre in Vero cells. MPA via
      depletion of substrate for polymerase (GTP), inhibited CHIKV induced apoptosis.
      By limiting the rate of de novo synthesis of guanosine nucleotide, MPA could
      apparently block the formation of the CHIKV progeny. The antiviral activity of
      MPA against Chikungunya virus is mediated through depletion of GTP pool via
      inhibition of IMPDH as demonstrated by Immunoblotting and different microscopic
      analysis.

PMID- 21070811
TI  - Oligomeric proanthocyanidins from Rumex acetosa L. inhibit the attachment of
      herpes simplex virus type-1.
AB  - The polyphenole-enriched acetone-water extract R2 from the aerial parts of Rumex
      acetosa L. containing high amounts of oligomeric and polymeric proanthocyanidins
      and flavonoids was tested for antiviral activity. R2 exhibited strong antiviral
      activity against herpes simplex virus type-1 (HSV-1) while the replication of
      adenovirus 3 was not affected. By plaque reduction test and MTT assay on Vero
      cells, the HSV-1-specific inhibitory concentration (IC(50)) and cytotoxic
      concentration (CC(50)) were determined. R2 exibited an IC(50) of 0.8 MUg/mL and a
      selectivity index (SI) (ratio of IC(50) to CC(50)) of approximately 100 when
      added to the virus inoculum for 1h at 37 degrees C prior to infection. The
      antiviral activity was due to the presence of flavan-3-ols and oligomeric
      proanthocyanidins in the extract. Structure-activity analyses indicated that
      flavan-3-ols and proanthocyanidins with galloylation at position O-3 are highly
      potent compounds (SI>40), while ungalloylated compounds did not exhibit antiviral
      effects (SI<1). R2 and a major proanthocyanidin from R2, epicatechin-3-O-gallate
      (4beta->8)-epicatechin-3-O-gallate abolished virus entry into the host cell by
      blocking attachment to the cell surface. When added after attachment at a
      concentration of >= 12.5 MUg/mL, R2 inhibited also penetration of HSV-1 into the
      host cell. R2 and epicatechin-3-O-gallate-(4beta->8)-epicatechin-3-O-gallate were
      shown to directly interact with viral particles leading to the oligomerisation of
      envelope proteins as demonstrated for the essential viral glycoprotein gD. Using
      raft cultures with three-dimensional organotypic human skin equivalents it was
      shown that treatment of cultures with R2 after infection with HSV-1 resulted in a
      reduced viral spread.

PMID- 21070812
TI  - Genotypic and phenotypic resistance of pandemic A/H1N1 influenza viruses
      circulating in Germany.
AB  - In response to the rapid global spread of an antigenically novel A/H1N1 influenza
      virus in 2009, the World Heath Organization (WHO) recommended surveillance and
      monitoring for antiviral resistance of influenza viruses. We designed and
      evaluated pyrosequencing (PSQ)-based genotypic assays for high-throughput
      analysis of the susceptibility of pandemic A/H1N1 influenza viruses to
      neuraminidase (NA) inhibitors. A total of 1570 samples circulating in Germany
      between April 2009 and April 2010 were tested for determination of molecular
      markers of resistance to the NA inhibitors oseltamivir and zanamivir, and 635 of
      them were evaluated by phenotypic fluorescence-based assay with MUNANA substrate.
      Eight (0.5%) viruses were resistant to oseltamivir due to the H274Y NA
      substitution (N2 numbering). Six of these oseltamivir-resistant cases were
      treatment-related; four of them were selected in immunocompromised patients, two
      in patients suffered from chronic diseases. The two remaining oseltamivir
      resistant viruses seem to have evolved in the absence of drug treatment and were
      isolated from immunocompetent healthy patients. All tested A/H1N1 pandemic
      viruses were sensitive to zanamivir. In addition, analysis of 1011 pandemic
      A/H1N1 virus samples by a PSQ-based assay according to the WHO protocol revealed
      the presence of mutation S31N in the M2 protein that conferred resistance to M2
      ion channel inhibitors. Our data demonstrate a low incidence of oseltamivir
      resistant pandemic A/H1N1 influenza variants isolated under drug selection
      pressure as well as community-acquired or naturally evolving viruses.

PMID- 21070814
TI  - Acute treatment with cannabinoid receptor agonist WIN55212.2 improves prepulse
      inhibition in psychosocially stressed mice.
AB  - Cannabis, similar to psychosocial stress, is well known to exacerbate psychotic
      experiences and can precipitate psychotic episodes in vulnerable individuals.
      Cannabinoid receptors 1 (CB1) are widely expressed in the brain and are
      particularly important to mediate the effects of cannabis. Chronic cannabis use
      in patients and chronic cannabinoids treatment in animals is known to cause
      reduced prepulse inhibition (PPI). Similarly, chronic psychosocial stress in mice
      impairs PPI. In the present study, we investigated the synergistic effects of
      substances modulating the CB1-receptors and chronic psychosocial stress on PPI.
      For this purpose, adult C57Bl/6J mice were exposed to chronic psychosocial stress
      using the resident-intruder paradigm. The cannabinoid receptor agonist WIN55212.2
      served as a surrogate marker for the effects of cannabis in the brain. After
      exposure to stress mice were acutely injected with WIN55212.2 (3 mg/kg) with or
      without pre-treatment with Rimonabant (3 mg/kg), a specific CB1-receptor
      antagonist, and subjected to behavioral testing. Stressed mice displayed a higher
      vulnerability to WIN55212.2 in the PPI test than control animals. The effects of
      WIN55212.2 on PPI were antagonized by Rimonabant suggesting an involvement of CB1
      receptors in sensorimotor gating. Interestingly, WIN55212.2 increased PPI in
      psychosocially stressed mice although previous studies in rats showed the
      opposite effects. It may thus be possible, that depending on the doses of
      cannabinoids/CB1-receptor agonists applied and environmental conditions
      (psychosocial stress), opposite effects can be evoked in different experimental
      animals. Taken together, our data imply that CB1-receptors might play a crucial
      role in the synergistic effects of psychosocial stress and cannabinoids in brain.

PMID- 21070815
TI  - Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to
      bedding stimuli.
AB  - The trpc2 gene encodes an ion channel involved in pheromonal detection and is
      found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal
      aggression (offspring protection) is impaired and brain Fos expression in females
      in response to a male are reduced. Here we examine in lactating wild-type (WT)
      and KO mice behavioral and brain responses to different olfactory/pheromonal
      cues. Consistent with previous studies, KO dams exhibited decreased maternal
      aggression and nest building, but we also identified deficits in nighttime
      nursing and increases in pup weight. When exposed to the bedding tests, WT dams
      typically ignored clean bedding, but buried male-soiled bedding from unfamiliar
      males. In contrast, KO dams buried both clean and soiled bedding. Differences in
      brain Fos expression were found between WT and KO mice in response to either no
      bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a
      site of pheromonal signal processing, KO mice showed suppressed Fos activation in
      the anterior mitral layer relative to WT mice in response to clean and soiled
      bedding. However, in the medial and basolateral amygdala, KO mice showed a robust
      Fos response to bedding, suggesting that regions of the amygdala canonically
      associated with pheromonal sensing can be active in the brains of KO mice,
      despite compromised signaling from the vomeronasal organ. Together, these results
      provide further insights into the complex ways by which pheromonal signaling
      regulates the brain and behavior of the maternal female.

PMID- 21070816
TI  - Risk variants in the S100B gene, associated with elevated S100B levels, are also
      associated with visuospatial disability of schizophrenia.
AB  - Rs9722 and rs1051169 have been reported as affecting the levels of S100B in the
      serum or the brain, and haplotypes containing these two SNPs have been associated
      with schizophrenia. The current study investigated the role of the S100B gene in
      an endophenotype of schizophrenia-spatial disability. 304 schizophrenia patients
      and 196 healthy controls were given a block design task and a mental rotation
      task. Results showed that the two aforementioned SNPs and related haplotypes were
      associated with the spatial disability of schizophrenia patients. Specifically,
      risk factors for the elevated S100B levels, including the A allele of rs9722, the
      G allele of rs1051169, and the AG haplotype, were associated with a poorer
      performance on both tests of spatial ability, especially the mental rotation
      task. These results implicate a role for S100B gene polymorphisms in the
      cognitive functions of schizophrenia patients and encourage further investigation
      into spatial disability as an endophenotype of schizophrenia.

PMID- 21070813
TI  - Sensitivity of seven HIV subtyping tools differs among subtypes/recombinants in
      the Spanish cohort of naive HIV-infected patients (CoRIS).
AB  - BACKGROUND: HIV-1 group M is classified into 9 subtypes and recombinants
      (CRFs/URFs). Variants other than subtype B (non-B) cause 90% of infections
      worldwide. HIV is often subtyped using automated tools instead of the gold
      standard phylogenetic analysis. We evaluated the reliability of subtyping tools
      vs. phylogeny in a panel of HIV-1 pol sequences from the cohort of naive patients
      of the HIV/AIDS Spanish Research Network (CoRIS). METHODS: HIV-1 subtyping was
      performed using seven automated subtyping tools (Stanford, Geno2pheno, Rega,
      NCBI, EuResist, STAR, TherapyEdge) in HIV-1 pol sequences from 670 CoRIS patients
      previously subtyped by phylogeny (587 subtype B/83 non-B). Sensitivity with
      respect to phylogeny was assessed. RESULTS: Most tools correctly classified
      subtype B, although up to 15% of non-B sequences were wrongly identified as B
      depending on the tool. For subtype B and CRF02_AG identification, Stanford/NCBI
      and Geno2pheno/Rega presented the highest/lowest sensitivities, respectively.
      EuResist and Geno2pheno correctly classified all 13 non-B "pure"subtypes at pol.
      The efficacy of all subtyping tools dropped clearly when identifying recombinants
      different from CRF02_AG. Only NCBI05, Rega and STAR identified URF, but with very
      low sensitivities. NCBI classified the highest number of subtypes B as non-B, and
      overestimated recombinants, especially when including references of 2009.
      CONCLUSIONS: Automated tools are useful for subtype B identification, although
      they present serious limitations in classifying variants uncommon in developed
      regions, especially recombinants. Their sensitivity depends on the prevalence of
      non-B variants in the population, and decreases drastically when the frequency of
      recombinants increases. Furthermore, HIV-1 variant distribution differs according
      to the tool used.

PMID- 21070817
TI  - The sedative but not the memory-blocking properties of ethanol are modulated by
      alpha5-subunit-containing gamma-aminobutyric acid type A receptors.
AB  - The precise mechanisms underlying the memory-blocking properties of ethanol are
      unknown, in part because ethanol targets a wide array of neurotransmitter
      receptors and transporters. The aim of this study was to determine whether the
      memory loss caused by ethanol is mediated, in part, by alpha5 subunit-containing
      gamma-aminobutyric acid subtype A receptors. These receptors have been implicated
      in learning and memory processes and are targets for a variety of neurodepressive
      drugs. Also, since these receptors generate a tonic inhibitory current in
      hippocampal pyramidal neurons, we examined whether concentrations of ethanol that
      block memory in vivo increased the tonic current using whole-cell patch-clamp
      recordings in hippocampal neurons. Null mutant mice lacking the alpha5 subunit
      (Gabra5-/-) and wild-type mice were equally impaired in contextual fear
      conditioning by moderate (1mg/kg) and high (1.5mg/kg) doses of ethanol. The
      higher dose of ethanol also reduced auditory delay fear conditioning to the same
      extent in the two genotypes. Interestingly, wild-type mice were more sensitive
      than Gabra5-/- mice to the sedative effects of low (0.5mg/kg) and moderate
      (1mg/kg) doses of ethanol in the open-field task. Concentrations of ethanol that
      impaired memory performance in vivo did not increase the amplitude of the tonic
      current. Together, the results suggest that the alpha5-subunit containing gamma
      aminobutyric acid subtype A receptors are not direct targets for positive
      modulation by ethanol nor do they contribute to ethanol-induced memory loss. In
      contrast, these receptors may contribute to the sedative properties of ethanol.

PMID- 21070818
TI  - Glutamate microinjection at the medial preoptic area enhances slow wave sleep in
      rats.
AB  - A large body of evidence has established the role of the medial preoptic area
      (mPOA) in regulation of slow wave sleep (SWS). Although the mPOA neurons contain
      excitatory neurotransmitter glutamate, its role in sleep-wakefulness is not
      known. In the present study microinjection of monosodium glutamate (40, 80 and
      120 ng) into the mPOA augmented SWS. Earlier reports have shown enhancement of
      paradoxical sleep by glutamate in other brain areas.

PMID- 21070819
TI  - Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model
      of Huntington's disease: morphological and behavioral outcomes.
AB  - Transplantation of mesenchymal stem cells (MSCs) may offer a viable treatment for
      Huntington's disease (HD). We tested the efficacy of MSC transplants to reduce
      deficits in a 3-nitropropionic acid (3NP) rat model of HD. Five groups of rats
      (Sham, 3NP, 3NP+vehicle, 3NP+TP(low), 3NP+TP(high)), were given PBS or 3NP
      intraperitoneally, twice daily for 42 days. On day 28, rats in all groups except
      Sham and 3NP, received intrastriatal injections of either 200,000 MSCs (TP(low)),
      400,000 (TP(high)) MSCs or DMEM (VH, the vehicle for transplantation). MSCs
      survived 72 days without inducing a strong inflammatory response from the
      striatum. Behavioral sparing was observed on tests of supported-hindlimb
      retraction, unsupported-hindlimb-retraction, visual paw placement and stepping
      ability for 3NP+TP(low) rats and on the unsupported-hindlimb-retraction and
      rotarod tasks for 3NP+VH rats. Relative to 3NP controls, all treated groups were
      protected from 3NP-induced enlargement of the lateral ventricles. In vitro, MSCs
      expressed transcripts for numerous neurotrophic factors. In vivo, increased
      striatal labeling in BDNF, collagen type-I and fibronectin (but not GDNF or CNTF)
      was observed in the brains of MSC-transplanted rats but not in DMEM-treated rats.
      In addition, none of the transplanted MSCs expressed neural phenotypes. These
      findings suggest that factors other than neuronal replacement underlie the
      behavioral sparing observed in 3NP rats after MSC transplantation.

PMID- 21070821
TI  - Extended access to methamphetamine self-administration affects sensorimotor
      gating in rats.
AB  - Disturbed information processing observed in neuropsychiatric disorders is
      reflected by deficient sensorimotor gating, measured as prepulse inhibition (PPI)
      of the acoustic startle response (ASR). Long-term, higher dose methamphetamine
      (METH) abuse patterns are associated with cognitive impairments, mania and/or
      schizophrenia-like psychosis. The present study investigated in rats METH-induced
      impairment of sensorimotor gating using an intravenous self-administration (IVSA)
      escalating dose procedure. In this procedure, rats escalated drug intake during
      weekly extended access periods to METH IVSA (1, 3, and 6h), where PPI was
      assessed after each access period and thus at various times of drug exposure.
      Despite increased drug intake over the course of extended access to METH,
      disruption of sensorimotor gating was only seen after the access period of 6h.
      The data suggest that METH-induced impairment of sensorimotor gating in IVSA
      tasks is rather attributed to continuous and higher dose exposure than to actual
      amounts of drug present at the time of testing. IVSA procedures, comprising
      stepwise stimulant escalation may serve as a useful translational model in rats
      that approximate important aspects of human abuse pattern in the context of
      stimulant-induced cognitive and behavioral deficits.

PMID- 21070823
TI  - Selected tetrapeptides lead to a GLP-1 release from the human enteroendocrine
      cell line NCI-H716.
AB  - Enteroendocrine cells in the intestine sense the luminal contents and have been
      shown to respond to not only fatty acids, proteins, and monosaccharides but also
      artificial sweeteners and bitter compounds. Secretion of hormones such as CCK and
      GLP-1 from these cells is often associated with a rise in intracellular calcium
      concentration [Ca2+](i). The human NCI-H716 enteroendocrine cell line has been
      described as a proper model to study GLP-1 secretion in response to amino acids
      and protein hydrolysates. Here, we describe that NCI-H716 cells specifically
      respond to selective tetrapeptides such as tetra-glycine, tetra-alanine and Gly
      Trp-Gly-Gly with a dose-dependent [Ca2+](i) response and a GLP-1 secretion,
      whereas selected free amino acids, dipeptides, tripeptides and pentapeptides
      failed to elicit such a response. Hormone secretion was not associated with
      changes in cAMP levels in the cells. The calcium-dependence of hormone secretion
      appears to involve store-operated calcium channels (SOCCs), since the SOCC
      blocker 2-APB abolished both the [Ca2+](i) response and GLP-1 release upon tetra
      glycine stimulation. The nature of the sensor currently remains elusive, and no
      obvious common structural pattern in tetrapeptides eliciting GLP-1 secretion was
      identified. This tetrapeptide sensing in NCI-H716 cells may be underlying the
      effective stimulation of hormone secretion shown for various protein
      hydrolysates, and could involve a novel G-protein-coupled receptor (GPCR).

PMID- 21070822
TI  - Acceleration of age-related learning and memory decline in middle-aged CD-1 mice
      due to maternal exposure to lipopolysaccharide during late pregnancy.
AB  - Previous studies have shown that inflammation process involves pathogenesis of
      Alzheimer's disease (AD). But, the natural AD model of inflammation has not been
      obtained yet. In the present study, CD-1 mothers intraperitoneally received a 50
      MUg/kg lipopolysaccharide (LPS) or normal saline daily during gestational days 15
      17. Body weight of the offspring was recorded at ages of 4-33 weeks. A different
      battery of behavioral tasks was, respectively, completed at ages of 35, 290 and
      400 days. The results showed that there was no significant difference in body
      weight between LPS-treated and control mice during ages of 4-33 weeks. LPS
      treated offspring had similar anxiety and locomotor behaviors, and spatial
      ability of learning and memory at the age of 35 days compared to the controls. At
      an age of 290 days, the LPS-treated offspring had similar sensorimotor ability,
      locomotor activity and anxiety, species-typical behaviors, and spatial ability of
      learning and memory. At an age of 400 days, there were similar sensorimotor
      ability, locomotor activity and anxiety between the LPS-treated offspring and
      controls. However, there were impaired species-typical behaviors, and spatial and
      non-spatial abilities of learning and memory in the LPS-treated offspring. Our
      results suggested that maternal exposure to LPS in adequate dose in late
      gestation can deliver term offspring which experience a normal duration of
      development and maturation, and an accelerated aged-related impairment in memory
      (spatial and non-spatial) and species-typical behaviors in middle-aged. These
      meet with the criteria of AD model in behaviors.

PMID- 21070820
TI  - Long-term voluntary wheel running is rewarding and produces plasticity in the
      mesolimbic reward pathway.
AB  - The mesolimbic reward pathway is implicated in stress-related psychiatric
      disorders and is a potential target of plasticity underlying the stress
      resistance produced by repeated voluntary exercise. It is unknown, however,
      whether rats find long-term access to running wheels rewarding, or if repeated
      voluntary exercise reward produces plastic changes in mesolimbic reward
      neurocircuitry. In the current studies, young adult, male Fischer 344 rats
      allowed voluntary access to running wheels for 6 weeks, but not 2 weeks, found
      wheel running rewarding, as measured by conditioned place preference (CPP).
      Consistent with prior reports and the behavioral data, 6 weeks of wheel running
      increased DeltaFosB/FosB immunoreactivity in the nucleus accumbens (Acb). In
      addition, semi quantitative in situ hybridization revealed that 6 weeks of wheel
      running, compared to sedentary housing, increased tyrosine hydroxylase (TH) mRNA
      levels in the ventral tegmental area (VTA), increased delta opioid receptor (DOR)
      mRNA levels in the Acb shell, and reduced levels of dopamine receptor (DR)-D2
      mRNA in the Acb core. Results indicate that repeated voluntary exercise is
      rewarding and alters gene transcription in mesolimbic reward neurocircuitry. The
      duration-dependent effects of wheel running on CPP suggest that as the weeks of
      wheel running progress, the rewarding effects of a night of voluntary wheel
      running might linger longer into the inactive cycle thus providing stronger
      support for CPP. The observed plasticity could contribute to the mechanisms by
      which exercise reduces the incidence and severity of substance abuse disorders,
      changes the rewarding properties of drugs of abuse, and facilitates successful
      coping with stress.

PMID- 21070824
TI  - Sumoylation regulates nuclear localization of repressor DREAM.
AB  - DREAM is a Ca(2+)-binding protein with specific functions in different cell
      compartments. In the nucleus, DREAM acts as a transcriptional repressor, although
      the mechanism that controls its nuclear localization is unknown. Yeast two-hybrid
      assay revealed the interaction between DREAM and the SUMO-conjugating enzyme Ubc9
      and bioinformatic analysis identified four sumoylation-susceptible sites in the
      DREAM sequence. Single K-to-R mutations at positions K26 and K90 prevented in
      vitro sumoylation of recombinant DREAM. DREAM sumoylation mutants retained the
      ability to bind to the DRE sequence but showed reduced nuclear localization and
      failed to regulate DRE-dependent transcription. In PC12 cells, sumoylated DREAM
      is present exclusively in the nucleus and neuronal differentiation induced
      nuclear accumulation of sumoylated DREAM. In fully differentiated trigeminal
      neurons, DREAM and SUMO-1 colocalized in nuclear domains associated with
      transcription. Our results show that sumoylation regulates the nuclear
      localization of DREAM in differentiated neurons. This article is part of a
      Special Issue entitled: 11th European Symposium on Calcium.

PMID- 21070825
TI  - Reversible blood-brain barrier disruption by repeated transcranial focused
      ultrasound allows enhanced extravasation.
AB  - The permeability of blood-brain barrier (BBB) for albumin can be enhanced by
      focused ultrasound (FUS) in a targeted region when this is applied in the
      presence of ultrasound contrast agent (UCA). In this study, we demonstrate that,
      using this noninvasive treatment, Evans Blue (EB) extravasation can be enhanced
      by repeated sonication. Sonications were applied at an ultrasound frequency of 1
      MHz with a 5% duty cycle, and a repetition frequency of 1 Hz. The brains of male
      Sprague-Dawley rats were subjected to FUS exposure at the same targeted site. At
      the same acoustic power, the extravasation caused by leakage of EB into the brain
      was found to be dependent on the applied sonication time. In vivo, both single
      and repeated sonications increased the extravasation of the albumin binding EB,
      especially for the repeated sonication group. In the retreatment experiment,
      there was a nearly twofold increase in EB extravasation in groups with a second
      sonication compared with the single sonication group. BBB disruption can be
      prolonged by repeated FUS sonication and the duration is dependent on the time
      point of the resonication after the first sonication. Compared to a single
      sonication, the MR imaging analysis and histological examination of the affected
      brains indicated that the pattern of contrast enhancement was changed and that
      vacuolation occurred after repeated sonication. This noninvasive technology
      offers the possibility of controlling the extent of drug delivery by means of
      repeated treatment and adjusting the duration and interval between sonications.

PMID- 21070826
TI  - Preparation of budesonide-loaded porous PLGA microparticles and their therapeutic
      efficacy in a murine asthma model.
AB  - Inhaling corticosteroids, such as budesonide (BD), is the most common treatment
      for asthma. However, frequent steroid administration is associated with many side
      effects. We hypothesized that porous microparticles containing BD could provide
      an effective treatment method for asthma, as the sustained delivery of
      corticosteroid and a reduced number of doses could be achieved using porous
      polymeric microparticles. Porous microparticles were prepared from poly(lactic-co
      glycolic acid) (PLGA) by a water-in-oil-in-water double emulsion method with
      ammonium bicarbonate as the porogen. Varying the porogen concentration controlled
      the morphology, particle size, and pore size of the PLGA microparticles, with
      particle size and pore size increasing as the porogen concentration increased.
      The BD loading efficiency in the porous PLGA microparticles was about 60%, and BD
      was released from the porous microparticles in a sustained manner for 24h in
      vitro. Lung uptake efficiency of the porous PLGA microparticles in mice was
      significantly higher than that of non-porous PLGA microparticles. Budesonide
      loaded porous PLGA microparticles were delivered to asthmatic mice, and the
      numbers of inflammatory cells in bronchoalveolar lavage (BAL) fluid and tissue
      sections were significantly reduced when the drug was administrated every 3days.
      We also found significantly reduced bronchial hyperresponsiveness of asthmatic
      mice after treatment with budesonide-loaded porous PLGA microparticles. This
      approach to controlling the porous structure of polymeric microparticles, as well
      as the release behavior of drugs from the microparticles, could have useful
      applications in the pulmonary delivery of many therapeutic drugs.

PMID- 21070827
TI  - Relationship between perceived stress and dietary and activity patterns in older
      adults participating in the Boston Puerto Rican Health Study.
AB  - Previous research supports a relationship between psychological stress and
      chronic disease in Puerto Rican adults living in the Boston, Massachusetts area.
      Stress may affect health by influencing dietary and physical activity patterns.
      Therefore, perceived stress and two hypothesized mediators of stress-related food
      intake, insulin and cortisol, were examined for possible associations with
      dietary and activity patterns in >1300 Puerto Ricans (aged 45-75 years; 70%
      women) living in the Boston, Massachusetts area. Data were analyzed using
      multiple linear regression and ANCOVA. Greater perceived stress was associated
      with lower fruit, vegetable, and protein intake, greater consumption of salty
      snacks, and lower participation in physical activity. Stress was associated with
      higher intake of sweets, particularly in those with type 2 diabetes. Cortisol and
      stress were positively associated in those without diabetes. Cortisol was
      associated with higher intake of saturated fat and, in those with diabetes, sweet
      foods. Independent of diabetes, perceived stress was associated with higher
      circulating insulin and BMI. Our findings support a link between stress,
      cortisol, and dietary and activity patterns in this population. For high-sugar
      foods, this relationship may be particularly important in those with type 2
      diabetes. Longitudinal research to determine causal pathways for these identified
      associations is warranted.

PMID- 21070829
TI  - The ketogenic diet changes metabolite levels in hippocampal extracellular fluid.
AB  - Despite successful use of the ketogenic diet (KD) for the treatment of drug
      resistant epilepsy, its mechanism of action is unclear. After KD-feeding,
      increased plasma D-beta-hydroxybutyrate (BHB) levels appear to be important for
      protection against seizures. We hypothesized that the KD leads to metabolic
      changes in the brain, which are reflected in the hippocampal extracellular fluid
      (hECF). CD1 mice were fed control or KD for 2-3 weeks since weaning. In vivo
      microdialysis of hECF was used to measure the levels of glucose, lactate, as well
      as BHB under basal conditions and during 30 min stimulation with 60 mM K(+),
      which was retrodialysed. The hECF BHB concentration in KD-fed mice was determined
      as 43.4+/-10.1 MUM using the zero-flow method and 50.7+/-5.5 MUM based on in
      vitro recovery. The total BHB concentration in brain homogenate from KD-fed mice
      was 180 nmol/g. The intracellular BHB concentration is therefore estimated to be
      about 3-fold higher than the extracellular level, which suggests that BHB in
      adolescent mouse brains may not be quickly metabolized. The basal hECF glucose
      concentration was 30% lower in KD-fed mice, indicating that glucose may be less
      important as an energy source. Lactate levels were similar in control and KD-fed
      mice. High potassium stimulation elevated lactate by 3-3.5-fold and decreased
      glucose by 40-50% in both diet groups, consistent with similar anaerobic and
      aerobic metabolism in both diet groups during high hippocampal activity. Overall,
      these data (1) defined the BHB concentration in the hippocampal extracellular
      fluid in KD-fed mice and (2) showed lower glucose metabolism compared to control
      diet-fed mice. This work will now enable other researchers to mimic the
      hippocampal extracellular environment in experiments aimed at deciphering the
      mechanisms of the KD.

PMID- 21070828
TI  - The structure and allosteric regulation of glutamate dehydrogenase.
AB  - Glutamate dehydrogenase (GDH) has been extensively studied for more than 50
      years. Of particular interest is the fact that, while considered by most to be a
      'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide
      array of allosteric effectors and exhibits extensive inter-subunit communication.
      While the chemical mechanism for GDH has remained unchanged through epochs of
      evolution, it was not clear how or why animals needed to evolve such a finely
      tuned form of this enzyme. As reviewed here, recent studies have begun to
      elucidate these issues. Allosteric regulation first appears in the Ciliates and
      may have arisen to accommodate evolutionary changes in organelle function. The
      occurrence of allosteric regulation appears to be coincident with the formation
      of an 'antenna' like feature rising off the tops of the subunits that may be
      necessary to facilitate regulation. In animals, this regulation further evolved
      as GDH became integrated into a number of other regulatory pathways. In
      particular, mutations in GDH that abrogate GTP inhibition result in dangerously
      high serum levels of insulin and ammonium. Therefore, allosteric regulation of
      GDH plays an important role in insulin homeostasis. Finally, several compounds
      have been identified that block GDH-mediated insulin secretion that may be to not
      only find use in treating these insulin disorders but to kill tumors that require
      glutamine metabolism for cellular energy.

PMID- 21070830
TI  - Kinetic analyses and mathematical modeling of primary photochemical and
      photoelectrochemical processes in plant photosystems.
AB  - In this paper the model and simulation of primary photochemical and photo
      electrochemical reactions in dark-adapted intact plant leaves is presented. A
      descriptive algorithm has been derived from analyses of variable chlorophyll a
      fluorescence and P700 oxidation kinetics upon excitation with multi-turnover
      pulses (MTFs) of variable intensity and duration. These analyses have led to
      definition and formulation of rate equations that describe the sequence of
      primary linear electron transfer (LET) steps in photosystem II (PSII) and of
      cyclic electron transport (CET) in PSI. The model considers heterogeneity in PSII
      reaction centers (RCs) associated with the S-states of the OEC and incorporates
      in a dark-adapted state the presence of a 15-35% fraction of Q(B)-nonreducing RCs
      that probably is identical with the S0 fraction. The fluorescence induction
      algorithm (FIA) in the 10 MUs-1s excitation time range considers a photochemical
      O-J-D, a photo-electrochemical J-I and an I-P phase reflecting the response of
      the variable fluorescence to the electric trans-thylakoid potential generated by
      the proton pump fuelled by CET in PSI. The photochemical phase incorporates the
      kinetics associated with the double reduction of the acceptor pair of pheophytin
      (Phe) and plastoquinone Q(A) [PheQ(A)] in Q(B) nonreducing RCs and the associated
      doubling of the variable fluorescence, in agreement with the three-state trapping
      model (TSTM) of PS II. The decline in fluorescence emission during the so called
      SMT in the 1-100s excitation time range, known as the Kautsky curve, is shown to
      be associated with a substantial decrease of CET-powered proton efflux from the
      stroma into the chloroplast lumen through the ATPsynthase of the photosynthetic
      machinery.

PMID- 21070831
TI  - The emergence of synchronization behavior in Physarum polycephalum and its
      particle approximation.
AB  - The regeneration process of contractile oscillation in the plasmodium of Physarum
      polycephalum is investigated experimentally and modelled computationally. When
      placed in a well, the Physarum cell restructures the body (fusion of small
      granule-like cells) and shows various complex oscillation patterns. After it
      completed the restructuring and regained synchronized oscillation within the
      body, the cell shows bilateral oscillation or rotating wave pattern. This
      regeneration process did not depend on the well size and all the cases tested
      here showed similar time course. Phase synchronization analysis based on Hilbert
      Transform also suggested that the cell can develop a fully synchronized
      oscillation within a fixed time no matter what the cell size is. A particle-based
      computational model was developed in order to model the emergence of oscillation
      patterns. Particles employing very simple and identical sensory and motor
      behaviors interacted with each other via the sensing and deposition of
      chemoattractants in a diffusive environment. From a random and almost homogeneous
      distribution, emergent domains of oscillatory activity emerged. By increasing the
      sensory radius the model simulated the regeneration process of the real
      plasmodium. In addition, the model replicated the rotating wave and bilateral
      oscillation pattern when the sensory radius was increased. The results suggest
      that complex emergent oscillatory behaviors (and thus the high-level systems
      which may utilize them, such as pumping and transport mechanisms) may be
      developed from simple materials inspired by Physarum slime mold.

PMID- 21070832
TI  - Rhodobase, a meta-analytical tool for reconstructing gene regulatory networks in
      a model photosynthetic bacterium.
AB  - We present Rhodobase, a web-based meta-analytical tool for analysis of
      transcriptional regulation in a model anoxygenic photosynthetic bacterium,
      Rhodobacter sphaeroides. The gene association meta-analysis is based on the
      pooled data from 100 of R. sphaeroides whole-genome DNA microarrays. Gene-centric
      regulatory networks were visualized using the StarNet approach (Jupiter, D.C.,
      VanBuren, V., 2008. A visual data mining tool that facilitates reconstruction of
      transcription regulatory networks. PLoS ONE 3, e1717) with several modifications.
      We developed a means to identify and visualize operons and superoperons. We
      designed a framework for the cross-genome search for transcription factor binding
      sites that takes into account high GC-content and oligonucleotide usage profile
      characteristic of the R. sphaeroides genome. To facilitate reconstruction of
      directional relationships between co-regulated genes, we screened upstream
      sequences (-400 to +20bp from start codons) of all genes for putative binding
      sites of bacterial transcription factors using a self-optimizing search method
      developed here. To test performance of the meta-analysis tools and transcription
      factor site predictions, we reconstructed selected nodes of the R. sphaeroides
      transcription factor-centric regulatory matrix. The test revealed regulatory
      relationships that correlate well with the experimentally derived data. The
      database of transcriptional profile correlations, the network visualization
      engine and the optimized search engine for transcription factor binding sites
      analysis are available at http://rhodobase.org.

PMID- 21070834
TI  - The crosstalks between adipokines and catecholamines.
AB  - Adipocytes, which secrete a spectrum of adipokines, play an integral role in
      metabolism via communications with other endocrine cells. In the present work, we
      have studied the interplays between adipokines and catecholamines, using 3T3-L1
      adipocytes and PC12 cells as the cell models and an integrative experimental
      platform. We demonstrate that all catecholamines inhibit vesicle trafficking and
      secretion of leptin and resistin through beta-adrenergic receptors, while leptin
      and resistin enhance the vesicle trafficking and secretion of catecholamines
      through PKC, PKA, MAPK kinase and Ca(2+) dependent pathways. The crosstalks
      between adipokines and catecholamines were further corroborated by co-culturing
      3T3-L1 adipocytes and PC12 cells. Our findings highlight the importance of adipo
      adrenal axis in energy metabolism and the intricate interactions between
      metabolic hormones.

PMID- 21070833
TI  - Consequences of POR mutations and polymorphisms.
AB  - P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal
      cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro.
      Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the
      Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis
      (causing genital anomalies), but the basis of ABS is unclear. We have
      characterized the activities of ~40 POR variants, showing that assays based on
      P450c17 activities, but not cytochrome c assays, correlate with the clinical
      phenotype. The human POR gene is highly polymorphic: the A503V sequence variant,
      which decreases P450c17 activities to ~60%, is found on ~28% of human alleles. A
      promoter polymorphism (~8% of Asians and ~13% of Caucasians) at -152 reduces
      transcriptional activity by half. Screening of 35 POR variants showed that most
      mutants lacking activity with P450c17 or cytochrome c also lacked activity to
      support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug
      substrate), although there were some remarkable differences: Q153R causes ABS and
      has ~30% of wild-type activity with P450c17 but had 144% of WT activity with
      CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which
      metabolizes nearly 50% of clinically used drugs, was examined with multiple,
      clinically relevant drug substrates, showing that A287P and R457H dramatically
      reduce drug metabolism, and that A503V variably impairs drug metabolism. The
      degree of activity can vary with the drug substrate assayed, as the drugs can
      influence the conformation of the P450. POR is probably an important contributor
      to genetic variation in both steroidogenesis and drug metabolism.

PMID- 21070835
TI  - Chronic mild stress damages mitochondrial ultrastructure and function in mouse
      brain.
AB  - Increasing evidence implicates mitochondrial failure as a crucial factor in the
      pathogenesis of mental disorders, such as depression. The aim of the present
      study was to investigate the effects of exposure to chronic mild stress (CMS), a
      paradigm developed in the late 1980s as an animal model of depression, on the
      mitochondrial function and mitochondrial ultrastructure in the mouse brain. The
      results showed that the CMS regime induced depressive-like symptoms in mice
      characterized by reduced sucrose preference and body weight. Moreover, CMS
      exposure was associated with a significant increase in immobility time in the
      tail suspension test. Exposure to the CMS paradigm inhibited mitochondrial
      respiration rates and dissipated mitochondrial membrane potential in hippocampus,
      cortex and hypothalamus of mice. In addition, we found a damaged mitochondrial
      ultrastructure in brains of mice exposed to CMS. These findings provide evidence
      for brain mitochondrial dysfunction and ultrastructural damage in a mouse model
      of depression. Moreover, these findings suggest that mitochondrial malfunction
      induced oxidative injury could play a role in stress-related disorders such as
      depression.

PMID- 21070836
TI  - Human galectin-3 (Mac-2 antigen): defining molecular switches of affinity to
      natural glycoproteins, structural and dynamic aspects of glycan binding by
      flexible ligand docking and putative regulatory sequences in the proximal
      promoter region.
AB  - BACKGROUND: Human galectin-3 (Mac-2 antigen) is a cell-type-specific
      multifunctional effector owing to selective binding of distinct cell-surface
      glycoconjugates harboring beta-galactosides. The structural basis underlying the
      apparent preferences for distinct glycoproteins and for expression is so far
      unknown. METHODS: We strategically combined solid-phase assays on 43 natural
      glycoproteins with a new statistical approach to fully flexible computational
      docking and also processed the proximal promoter region in silico. RESULTS: The
      degree of branching in N-glycans and clustering of core 1 O-glycans are positive
      modulators for avidity. Sialylation of N-glycans in alpha2-6 linkage and of core
      1 O-glycans in alpha2-3 linkage along with core 2 branching was an unfavorable
      factor, despite the presence of suited glycans in the vicinity. The lectin-ligand
      contact profile was scrutinized for six natural di- and tetrasaccharides enabling
      a statistical grading by analyzing flexible docking trajectories. The
      computational analysis of the proximal promoter region delineated putative sites
      for Lmo2/c-Ets-1 binding and new sites with potential for RUNX binding. GENERAL
      SIGNIFICANCE: These results identify new features of glycan selectivity and
      ligand contact by combining solid-phase assays with in silico work as well as of
      reactivity potential of the promoter.

PMID- 21070837
TI  - Effect of prenatal pentylenetetrazol-induced kindling on learning and memory of
      male offspring.
AB  - Current data concerning the effects of maternal seizure during pregnancy on
      newborns are limited. This study was carried out to investigate the effect of
      prenatal pentylenetetrazol (PTZ)-induced kindling on learning and memory of
      offspring. Female Wistar rats were kindled with i.p. injections of 25 mg/kg of
      PTZ on day 13 of their pregnancy. The spatial performance and passive avoidance
      learning of pups were tested at 7 weeks and 12 weeks of age using Morris water
      maze (MWM) task and shuttle-box apparatus, respectively. We found, for the first
      time, that prenatal exposure to maternal seizure induced by PTZ leads to a
      significant impairment of learning and memory. In addition, the number of live
      birth was significantly lower in kindled rats compared to control. In MWM
      studies, the young offspring of kindled rats had poor spatial learning ability.
      The frequent tonic-clonic seizures in pregnancy was also associated with a poor
      memory as evidenced by decrease in distance swam in the target quadrant by the
      offspring of the kindled mother in the adulthood. Data obtained from shuttle-box
      studies showed that retention latencies of pups born to kindled dams were
      significantly reduced compared to those born to control dams. The hippocampus,
      amygdala and frontal cortex are very important for memory consolidation and our
      data suggest that subsequent developmental events are not sufficient to overcome
      the adverse effects of prenatal exposure to maternal seizures to these regions of
      the brain. These observations may have clinical implications for cognitive and
      memory dysfunction associated with epilepsy during pregnancy.

PMID- 21070838
TI  - The effects of embryonic knockdown of the candidate dyslexia susceptibility gene
      homologue Dyx1c1 on the distribution of GABAergic neurons in the cerebral cortex.
AB  - Developmental dyslexia is a language-based learning disability, and a number of
      candidate dyslexia susceptibility genes have been identified, including DYX1C1,
      KIAA0319, and DCDC2. Knockdown of function by embryonic transfection of small
      hairpin RNA (shRNA) of rat homologues of these genes dramatically disrupts
      neuronal migration to the cerebral cortex by both cell autonomous and non-cell
      autonomous effects. Here we sought to investigate the extent of non-cell
      autonomous effects following in utero disruption of the candidate dyslexia
      susceptibility gene homolog Dyx1c1 by assessing the effects of this disruption on
      GABAergic neurons. We transfected the ventricular zone of embryonic day (E) 15.5
      rat pups with either Dyx1c1 shRNA, DYX1C1 expression construct, both Dyx1c1 shRNA
      and DYX1C1 expression construct, or a scrambled version of Dyx1c1 shRNA, and
      sacrificed them at postnatal day 21. The mothers of these rats were injected with
      BrdU at either E13.5, E15.5, or E17.5. Neurons transfected with Dyx1c1 shRNA were
      bi-modally distributed in the cerebral cortex with one population in heterotopic
      locations at the white matter border and another migrating beyond their expected
      location in the cerebral cortex. In contrast, there was no disruption of
      migration following transfection with the DYX1C1 expression construct. We found
      untransfected GABAergic neurons (parvalbumin, calretinin, and neuropeptide Y) in
      the heterotopic collections of neurons in Dyx1c1 shRNA treated animals,
      supporting the hypothesis of non-cell autonomous effects. In contrast, we found
      no evidence that the position of the GABAergic neurons that made it to the
      cerebral cortex was disrupted by the embryonic transfection with any of the
      constructs. Taken together, these results support the notion that neurons within
      heterotopias caused by transfection with Dyx1c1 shRNA result from both cell
      autonomous and non-cell autonomous effects, but there is no evidence to support
      non-cell autonomous disruption of neuronal position in the cerebral cortex
      itself.

PMID- 21070839
TI  - A sex comparison of the anatomy and function of the main olfactory bulb-medial
      amygdala projection in mice.
AB  - We previously reported that some main olfactory bulb (MOB) mitral/tufted (M/T)
      cells send a direct projection to the "vomeronasal" amygdala in female mice and
      selectively respond to volatile male mouse urinary odors. We asked whether MOB
      M/T cells that project to the vomeronasal amygdala exist in male mice and whether
      there is a sexually dimorphic response of these neurons to volatile male urinary
      pheromones. Gonadectomized male and female mice received bilateral injections of
      the retrograde tracer, Cholera toxin-B (CTb) into the medial amygdala (Me), which
      is part of the vomeronasal amygdala. All subjects were then treated with
      estradiol benzoate and progesterone before being exposed to volatile male urinary
      odors whereupon they were sacrificed 90 min later. Sections of the MOB were
      immunostained for Fos protein and/or CTb. Male mice, like females, displayed a
      small population of MOB M/T cells that project to the Me. While the general
      localization of these cells was similar in the two sexes, there were
      statistically significant sex differences in the percentage of MOB M/T cells in
      the anterior and posterior medial segments of the MOB that were retrogradely
      labeled by CTb. Male urinary volatiles stimulated equivalent, significant
      increases in Fos expression by MOB M/T neurons projecting to the Me in the two
      sexes. By contrast, in the same mice exposure to male urinary volatiles
      stimulated a significant increase in Fos expression by mitral cells in the
      accessory olfactory bulb (AOB) only in female subjects. Thus any sexually
      dimorphic behavioral or neuroendocrine responses to male urinary volatiles likely
      depend on the differential processing of these odor inputs in the AOB and/or
      other downstream forebrain structures after their detection by the main olfactory
      system.

PMID- 21070840
TI  - Novel insights into CaMKII function and regulation during memory formation.
AB  - Ca(2+)/calmodulin-dependent kinase II (CaMKII) is an abundant synaptic signalling
      molecule that is essential for memory formation and the induction of synaptic
      potentiation. Additionally, CaMKII plays a prominent role in synaptic tagging and
      metaplasticity. These abilities are mediated by kinase activity as well as
      binding to a wide variety of synaptic proteins, including NMDA receptor subunits,
      modulating CaMKII location and activity. A characteristic feature is that
      autophosphorylation of CaMKII switches the kinase into autonomous activity. Since
      CaMKII can be autonomously active and because CaMKII is required for the
      formation of memory it is important that the kinase activity is adequately
      switched off. However, the exact time window of increased activity and how this
      is terminated, it is still matter of debate. After training in a memory task
      CaMKII activity is increased for at least 30 min. This CaMKII activity and
      further activation of CaMKII may be regulated by changes in the expression of two
      endogenous CaMKII inhibitor proteins, CaMKII inhibitor Alpha and Beta, as they
      are up-regulated early after training. These endogenous inhibitors specifically
      block CaMKII activity and they inhibit the association with NMDA receptor
      subunits. Thus, regulation of the expression of endogenous CaMKII inhibitors may
      constitute a novel negative feedback on CaMKII signalling during memory
      formation.

PMID- 21070841
TI  - Foraging behavior of the midday gerbil (Meriones meridianus): combined effects of
      distance and microhabitat.
AB  - We used the giving-up density (GUD) method and direct observation to study the
      combined effects of travel distance and microhabitat on foraging behavior of the
      midday gerbil (Meriones meridianus), which often acts as a central place forager.
      We provided animals with artificial seed trays in which dry and unhusked pumpkin
      seeds were mixed with fine sand. Gerbils practiced an eat-and-carry strategy in
      patches of bush microhabitat that were far from central places (BF patches), and
      tended to carry all seeds back in the other three treatments. Resource
      protection, predation risk avoidance and the balance between future and present
      value of food items may contribute to the eat-and-carry strategy. When distance
      was held constant, GUDs in open patches were higher than in bush patches, which
      was consistent with most studies. When microhabitat was held constant, GUDs in
      nearer patches were normally lower than in farther patches. In most cases,
      gerbils preferred to carry more seeds back rather than consume them immediately.
      We concluded that this tendency was due to the gerbils balancing the factors of
      future value and present value, and individual fitness and inclusive fitness.

PMID- 21070842
TI  - Oral drug delivery in personalized medicine: unmet needs and novel approaches.
AB  - Increasing knowledge into personalized medicine has demonstrated the need for
      individual dosing. Drug dosage forms are urgently needed enabling an individual
      therapy, especially for oral drug delivery. This review is focusing on approaches
      for solid and liquid oral dosage forms for individual dosing. The proposed dosage
      forms and devices may be distinguished into assembling and partition concepts and
      have been categorized regarding their applicability, costs, dose flexibility and
      potential benefits. Opportunities, challenges and further unmet needs are
      elaborated and critically discussed. Liquid dosage forms can be accurately dosed
      by novel dropping tubes or oral syringes, but less precisely by dosing spoons and
      cups. Breaking scored tablets into fragments show major risks such as inaccurate
      dosing, formation of potent dust and stability issues of the residual segments.
      Novel approaches are proposed for solid dosage forms enabling a flexible and
      appropriate therapy such as various dispensers for multiparticulate drug
      formulations. However, most of the proposals still have to prove their
      applicability in practice. Promising concepts are the solid dosage pen and drug
      loaded oral films which can be cut in individual sections enabling freely
      selectable doses. Further research and development are required for novel dosage
      forms and medical devices appropriate for individualized therapy.

PMID- 21070843
TI  - Cornus kousa F.Buerger ex Miquel increases glucose uptake through activation of
      peroxisome proliferator-activated receptor gamma and insulin sensitization.
AB  - AIM OF THE STUDY: Cornus kousa F.Buerger ex Miquel, an oriental medicinal plant,
      has been traditionally used for the treatment of hyperglycemia, but its molecular
      mechanism remains unknown. The goal of this study was to investigate the
      peroxisome proliferator-activated receptor gamma (PPARgamma) ligand-binding
      activity of Cornus kousa and to determine the effects of Cornus kousa on insulin
      sensitization in 3T3-L1 cells for the treatment of type 2 diabetes. MATERIALS AND
      METHODS: PPARgamma luciferase transactivation assay was used to evaluate the
      PPARgamma ligand-binding activity of Cornus kousa leaf extract. Western blot
      analysis, oil Red O staining, and glucose uptake assay were performed to evaluate
      PPARgamma agonistic activity and insulin sensitizing effects of Cornus kousa leaf
      extract (CKE) in 3T3-L1 cells. RESULTS: CKE increased PPARgamma ligand-binding
      activity in a dose-dependent manner. In addition, CKE enhanced adipogenesis and
      the expression of PPARgamma target proteins, including glucose transporter 4
      (GLUT4) and adiponectin, as well as proteins involved in adipogenesis, including
      PPARgamma and CCAAT/enhancer binding protein alpha (C/EBPalpha) in 3T3-L1
      adipocytes. Furthermore, CKE led to significant induction of glucose uptake and
      stimulated insulin signaling, but not to activation of AMP-activated protein
      kinase (AMPK) signaling. The enhanced glucose uptake by CKE were abolished by
      treatment with bisphenol a diglycidyl ether (BADGE), a PPARgamma antagonist, or
      LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), but not by compound
      C, an AMPK inhibitor. CONCLUSION: Consistent with the high PPARgamma ligand
      binding activity, CKE increased glucose uptake through PPARgamma activation and
      insulin signaling. These results suggest that CKE could have pharmacological
      effects for the treatment of hyperglycemia and type 2 diabetes.

PMID- 21070844
TI  - Anti-inflammatory effects of iridoid glycosides fraction of Folium syringae
      leaves on TNBS-induced colitis in rats.
AB  - AIM OF THE STUDY: To investigate the effects and the protective mechanism of
      iridoid glycosides (IG) enriched from Folium syringae leaves on ulcerative
      colitis (UC) model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats.
      MATERIALS AND METHODS: UC in rats was induced by colonic administration with
      TNBS. IG (80, 160 and 240 mg/kg) was administered for 2 weeks to experimental
      colitis rats. The inflammatory degree was assessed by macroscopic score,
      histology and myeloperoxidase (MPO) activity. Nitric oxide (NO) and
      malondialdehyde (MDA) levels were measured with biochemical methods. The protein
      expressions of nuclear factor-kappaBp65 (NF-kappaBp65) and mRNA expressions of
      pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6) and NF-kappaBp65, were determined by immunohistochemistry
      and real-time quantitative PCR, respectively. RESULTS: IG significantly
      ameliorated macroscopic damage and histological changes, reduced the activity of
      MPO, depressed MDA and NO levels and effectively inhibited the protein and mRNA
      expressions of NF-kappaBp65, TNF-alpha and IL-6 in the colon tissues of
      experimental colitis in a dose-dependent manner. Moreover, the effects of IG (160
      mg/kg and 240 mg/kg) were superior to salicylazosulfapyridine (150 mg/kg).
      CONCLUSION: We demonstrated for the first time that IG possessed marked
      protective effects on experimental colitis through its antioxidation and
      inhibiting inflammatory mediators by down-regulation of the expressions of NF
      kappaBp65.

PMID- 21070845
TI  - Methanolic extract of Hibiscus asper leaves improves spatial memory deficits in
      the 6-hydroxydopamine-lesion rodent model of Parkinson's disease.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: While the Hibiscus asper Hook.f. (Malvaceae) is a
      traditional herb largely used in tropical region of the Africa as vegetable,
      potent sedative, tonic and restorative, anti-inflammatory and antidepressive
      drug, there is very little scientific data concerning the efficacy of this. AIM
      OF THE STUDY: We investigated antioxidant activity and the effects of methanolic
      extract of Hibiscus asper leaves on neurological capacity of male Wistar rats
      subjected to unilateral 6-hydroxydopamine (6-OHDA)-lesion. MATERIALS AND METHODS:
      Two model systems: 2,4-dinitrophenyl-1-picryl hydrazyl (DPPH) radical scavenging
      activity and beta-carotene bleaching inhibition assay were used to measure the
      antioxidant activities of the plan extract. We also investigated the
      neuroprotective effect of methanolic extract of Hibiscus asper leaves (50 and 100
      mg/kg) in male Wistar rats subjected to unilateral 6-hydroxydopamine (6-OHDA)
      lesion rat model. RESULTS: Methanolic extract of Hibiscus asper leaves showed
      potent antioxidant and free radical scavenging activity. Chronic administration
      of methanolic extract (50 and 100 mg/kg, i.p., daily, for 7 days) significantly
      reduce anxiety-like behavior and inhibit depression in elevated plus-maze and
      forced swimming tests, suggesting anxiolytic and antidepressant activity. Also,
      spatial memory performance in Y-maze and radial arm-maze tasks was improved,
      suggesting positive effects on memory formation. CONCLUSIONS: Taken together, our
      results suggest that the methanolic extract of Hibiscus asper leaves have
      antioxidant effects and might provide an opportunity to management neurological
      abnormalities in Parkinson's disease conditions.

PMID- 21070846
TI  - The WNT/beta-catenin pathway mediates the anti-adipogenic mechanism of SH21B, a
      traditional herbal medicine for the treatment of obesity.
AB  - AIM OF THE STUDY: This study was conducted to elucidate the molecular mechanisms
      of SH21B, a traditional Korean herbal medicine commonly used for the treatment of
      obesity. MATERIALS AND METHODS: 3T3-L1 preadipocytes were differentiated into
      adipocytes in the presence or absence of SH21B. Changes in mRNA or protein levels
      were analyzed using microarray, real-time polymerase chain reaction and western
      blotting analyses. Small interference (si)RNA transfection experiments were
      conducted to elucidate the essential role of beta-catenin. RESULTS: Microarray
      analyses showed that components of the WNT/beta-catenin pathway including beta
      catenin, cyclin D1 and dishevelled 2 were up-regulated more than two-fold as a
      result of SH21B treatment during adipogenesis, which were confirmed by real-time
      PCR and western blotting. Modulation of the WNT/beta-catenin pathway by SH21B
      resulted in the nuclear accumulation of beta-catenin. Both intracellular lipid
      droplet formation and expressions of adipogenic genes including PPARgamma,
      C/EBPalpha, FABP4 and LPL, which were inhibited by SH21B, were significantly
      recovered by beta-catenin siRNA transfection. CONCLUSIONS: SH21B modulates
      components of the WNT/beta-catenin pathway during adipogenesis, and beta-catenin
      plays a crucial role in the anti-adipogenic mechanism of SH21B.

PMID- 21070847
TI  - A live attenuated Listeria monocytogenes vaccine vector expressing SIV Gag is
      safe and immunogenic in macaques and can be administered repeatedly.
AB  - Listeria monocytogenes (Lm) is known to induce strong cellular immune responses.
      We constructed a live-attenuated Lm vector, Lmdd-BdopSIVgag, which encodes
      SIVmac239 gag. Intragastric (i.g.) administration of 3 * 10(12) bacteria to
      rhesus macaques was safe and induced anti-Gag cellular but no humoral immune
      responses. Boosting of Gag-specific cellular responses was observed after i.g.
      administration of Lmdd-BdopSIVgag to previously vaccinated RM despite preexisting
      anti-Lm immunity shown by lymphoproliferative responses. Surprisingly, anti-Lm
      cellular responses were also detected in non-vaccinated controls, which may
      reflect the fact that Lm is a ubiquitous bacterium. The novel, live-attenuated
      Lmdd-BdopSIVgag may be an attractive platform for oral vaccine delivery.

PMID- 21070848
TI  - NOS-mediated morphological and molecular modifications in rats infused with Abeta
      (1-40), as a model of Alzheimer's disease, in response to a new lipophilic
      molecular combination codrug-1.
AB  - Alzheimer's disease is a neurodegenerative pathology due to the presence of beta
      amyloid plaques at brain level and hippocampus level and associated with the loss
      of memory speech and learning. At the basis of these effects lie molecular
      mechanisms which include nitric oxide metabolic pathway, whose involvement in the
      occurrence of morphological modifications related to such neurodegenerative
      process is suggested. Current evidences show that the non-steroidal anti
      inflammatory drug ibuprofen posses a protective effect against the development of
      the disease, substantially delaying its onset; furthermore (R)-alpha-lipoic acid
      seems to have an antioxidant ameliorating effect on disease progression. Starting
      from these data, a new lipophilic codrug 1, obtained by joining an antioxidant
      molecule with an NSAID, has been previously synthesized. Our aim has been to
      investigate the possible therapeutical effects of codrug 1, compared to
      ibuprofen, on the molecular events at the basis of behavioural and morphological
      modifications occurring in Abeta (1-40) infused rat brains. Ibuprofen and codrug
      1 seem to protect the subject against memory performance impairment and against
      behavioural detriment, induced by administration of Abeta (1-40) peptide. Such
      evidences are supported by morphological and biochemical findings showing Abeta
      (1-40) to determine cell disorganization, increased number of beta-amyloid
      plaques and capillary vessels dilatation in parallel to increased total and
      specific NOS activity and to apoptosis occurrence, partly prevented by ibuprofen,
      more broadly by codrug 1. Such results underline the involvement of nitric oxide
      metabolic pathway in the events related to the onset of this pathology and
      suggest codrug 1 as a useful tool to protect the brain against cognitive and
      behavioural dysfunction, by reducing beta-amyloid plaques formation and by
      inhibiting NOS signalling pathway and apoptosis occurrence.

PMID- 21070849
TI  - Dipyridamole reverses peripheral ischemia and induces angiogenesis in the Db/Db
      diabetic mouse hind-limb model by decreasing oxidative stress.
AB  - Dipyridamole anti-platelet therapy has previously been suggested to ameliorate
      chronic tissue ischemia in healthy animals. However, it is not known if
      dipyridamole therapy represents a viable approach to alleviating chronic
      peripheral tissue ischemia associated with type 2 diabetes. Here we examine the
      hypothesis that dipyridamole treatment restores reperfusion of chronic hind-limb
      ischemia in the murine B6.BKS-Lepr(db/db) diabetic model. Dipyridamole therapy
      quickly rectified ischemic hind-limb blood flow to near preligation levels within
      3 days of the start of therapy. Restoration of ischemic tissue blood flow was
      associated with increased vascular density and endothelial cell proliferation
      observed only in ischemic limbs. Dipyridamole significantly increased total
      nitric oxide metabolite levels in tissue, which were not associated with changes
      in endothelial NO synthase expression or phosphorylation. Interestingly,
      dipyridamole therapy significantly decreased ischemic tissue superoxide and
      protein carbonyl levels, identifying a dominant antioxidant mechanistic response.
      Dipyridamole therapy also moderately reduced diabetic hyperglycemia and
      attenuated development of dyslipidemia over time. Together, these data reveal
      that dipyridamole therapy is an effective modality for the treatment of chronic
      tissue ischemia during diabetes and highlights the importance of dipyridamole
      antioxidant activity in restoring tissue NO bioavailability during diabetes.

PMID- 21070850
TI  - Folate deficiency regulates expression of DNA polymerase beta in response to
      oxidative stress.
AB  - Folate deficiency has been shown to influence carcinogenesis by creating an
      imbalance in the base excision repair (BER) pathway, affecting BER homeostasis.
      The inability to mount a BER response to oxidative stress in a folate-deficient
      environment results in the accumulation of DNA repair intermediates, i.e., DNA
      strand breaks. Our data indicate that upregulation of beta-pol expression in
      response to oxidative stress is inhibited by folate deficiency at the level of
      gene expression. Alteration in the expression of beta-pol in a folate-deficient
      environment is not due to epigenetic changes in the core promoter of the beta-pol
      gene, i.e., the CpG islands within the beta-pol promoter remain unmethylated in
      the presence or absence of folate. However, the promoter analysis studies show a
      differential binding of regulatory factors to the -36 to -7 region (the folic
      acid-response region, FARR) within the core promoter of beta-pol. Moreover, we
      observe a tight correlation between the level of binding of regulatory factors
      with the FARR and inhibition of beta-pol expression. Based on these findings, we
      propose that folate deficiency results in an upregulation/stability of negative
      regulatory factors interacting with FARR, repressing the upregulation of the beta
      pol gene in response to oxidative stress.

PMID- 21070851
TI  - Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced
      myocardial tissue injury.
AB  - Previous studies have suggested that increased levels of endocannabinoids in
      various cardiovascular disorders (e.g., various forms of shock, cardiomyopathies,
      atherosclerosis) through the activation of CB(1) cannabinoid receptors may
      promote cardiovascular dysfunction and tissue injury. We have investigated the
      role of the main endocannabinoid anandamide-metabolizing enzyme (fatty acid amide
      hydrolase; FAAH) in myocardial injury induced by an important chemotherapeutic
      drug, doxorubicin (DOX; known for its cardiotoxicity mediated by increased
      reactive oxygen and nitrogen species generation), using well-established acute
      and chronic cardiomyopathy models in mice. The DOX-induced myocardial
      oxidative/nitrative stress (increased 4-hydroxynonenal, protein carbonyl, and
      nitrotyrosine levels and decreased glutathione content) correlated with multiple
      cell death markers, which were enhanced in FAAH knockout mice exhibiting
      significantly increased DOX-induced mortality and cardiac dysfunction compared to
      their wild type. The effects of DOX in FAAH knockouts were attenuated by CB(1)
      receptor antagonists. Furthermore, anandamide induced enhanced cell death in
      human cardiomyocytes pretreated with FAAH inhibitor and enhanced sensitivity to
      ROS generation in inflammatory cells of FAAH knockouts. These results suggest
      that in pathological conditions associated with acute oxidative/nitrative stress
      FAAH plays a key role in controlling the tissue injury that is, at least in part,
      mediated by the activation of CB(1) receptors by endocannabinoids.

PMID- 21070852
TI  - Association of supervillin with KIR2DL1 regulates the inhibitory signaling of
      natural killer cells.
AB  - Inhibitory signaling is crucial in the regulation of the cytotoxicity of natural
      killer (NK) cells. Here, we show that KIR2DL1, an inhibitory receptor of NK
      cells, associates with supervillin, an F-actin binding protein. Interaction of
      supervillin with KIR2DL1 is dependent on the KIR2DL1 receptor stimulation and
      requires the phosphorylation of tyrosines in both ITIM motifs. "Knockdown" of
      expression of supervillin by RNA interference (RNAi) restores the KIR2DL1
      suppressed cytotoxicity of NK cells. Inhibition of supervillin by RNAi also
      enhances the polarization of cytolytic granules (both granzyme B and perforin) to
      the synapse formed between YTS-GFP-KIR2DL1 NK cells and 721.221-HLA-Cw4 target
      cells. Further study reveals that supervillin is required for KIR2DL1-mediated
      inhibition of Vav1 and ERK phoshorylation. Moreover, we have found that binding
      of supervillin with KIR2DL1 facilitates the recruitment of SHPs especially SHP-2
      to KIR2DL1 receptor. Thus, our findings demonstrate that supervillin is a novel
      molecule that associates with KIR2DL1 receptor and regulates the inhibitory
      signaling in NK cells.

PMID- 21070853
TI  - A novel role for c-Jun N-terminal kinase and phosphoinositide 3-kinase in the
      liver X receptor-mediated induction of macrophage gene expression.
AB  - Liver X receptors (LXRs) are ligand-dependent transcription factors that are
      activated by metabolites of cholesterol, oxysterols, and a number of synthetic
      agonists. LXRs play potent anti-atherogenic roles in part by stimulating the
      efflux of cholesterol from macrophage foam cells. The LXR-induced expression of
      ATP-binding cassette transporter (ABC)-A1 and Apolipoprotein E (ApoE) in
      macrophages is essential for the stimulation of cholesterol efflux and the
      prevention of atherosclerotic development. Unfortunately, the signaling pathways
      underlying such regulation are poorly understood and were therefore investigated
      in human macrophages. The expression of ApoE and ABCA1 induced by synthetic or
      natural LXR ligands [TO901317, GW3965, and 22-(R)-hydroxycholesterol (22-(R)-HC),
      respectively] was attenuated by inhibitors of c-Jun N-terminal kinase (JNK)
      (curcumin and SP600125) and phosphoinositide 3-kinase (PI3K) (LY294002). Similar
      results were obtained with ABCG1 and LXR-alpha, two other LXR target genes. LXR
      agonists activated several components of the JNK pathway (SEK1, JNK and c-Jun)
      along with AKT, a downstream target for PI3K. In addition, dominant negative
      mutants of JNK and PI3K pathways inhibited the LXR-agonists-induced activity of
      the ABCA1 and LXR-alpha gene promoters in transfected cells. LXR agonists also
      induced the binding of activator protein-1 (AP-1), a key transcription factor
      family regulated by JNK, to recognition sequences present in the regulatory
      regions of the ApoE and ABCA1 genes. These studies reveal a novel role for JNK
      and PI3K/AKT signaling in the LXR-regulated expression in macrophages of several
      key genes implicated in atherosclerosis.

PMID- 21070854
TI  - WNT-5A stimulates the GDP/GTP exchange at pertussis toxin-sensitive
      heterotrimeric G proteins.
AB  - The lipoglycoproteins of the WNT family act on seven transmembrane-spanning Class
      Frizzled receptors. Here, we show that WNT-5A evokes a proliferative response in
      a mouse microglia-like cell line (N13), which is sensitive to pertussis toxin,
      thus implicating the involvement of heterotrimeric G proteins of the G(i/o)
      family. We continue to show that WNT-5A stimulation of N13 membranes and
      permeabilized cells evokes the exchange of GDP for GTP of pertussis toxin
      sensitive G proteins employing [gamma-(35)S]GTP assay and activity state-specific
      antibodies to GTP-bound G(i) proteins. Our functional analysis of the PTX
      sensitivity of WNT-induced G protein activation and PCR analysis of G protein and
      FZD expression patterns suggest that WNT-5A stimulation leads to the activation
      of G(i2/3) proteins in N13 cells possibly mediated by FZD(5), the predominant FZD
      expressed. In summary, we provide for the first time molecular proof that WNT-5A
      stimulation results in the activation of heterotrimeric G(i2/3) proteins in
      mammalian cells with physiological protein stochiometry.

PMID- 21070855
TI  - Mutation of a novel virulence-related gene mltD in Vibrio anguillarum enhances
      lethality in zebra fish.
AB  - Vibrio anguillarum, a halophilic Gram-negative bacterium, is the causative agent
      of vibriosis, which is a major problem for the aquaculture industry worldwide.
      Previously, a virulence-related gene fragment of V. anguillarum was obtained from
      a suppression subtractive hybridization (SSH) library. In this study, the
      complete gene sequence was obtained by long and accurate PCR (LA-PCR). After
      sequence analysis and homologous comparison, this new virulence-related gene was
      revealed to encode a putative membrane-bound lytic murein transglycosylase D
      (MltD), which consisted of 547 amino acids, and showed 34% identity to the MltD
      in Escherichia coli. An mltD mutant of pathogenic V. anguillarum CW-1 was
      constructed by homologous recombination. Production of extracellular gelatinase
      and protease of the mltD mutant decreased markedly compared with those of the
      wild-type strain, and the hemolytic activity was totally lost. Sodium chloride
      challenge and antibiotic sensitivity assay showed that the resistance of the mltD
      mutant to high concentrations of sodium chloride, and rocephin, fortun, cefobid,
      gentamicin, kanamycin and carbenicillin was enhanced. Most importantly, virulence
      of the mltD mutant was enhanced compared with that of the wild type when it was
      inoculated intraperitoneally into zebra fish; the LD50 of the wild type and the
      mutant was 3.92 * 103 CFU and 1.01 * 102 CFU fish-1, respectively. The mltD was
      cloned and overexpressed in E. coli, and the recombinant MltD protein showed
      hemolytic, phospholipase, gelatinase and diastase activities. This is the first
      report that MltD possibly has a virulence-related function.

PMID- 21070857
TI  - No evidence for involvement of donor NK cells in liver transplant tolerance.

PMID- 21070856
TI  - Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft
      versus-host disease after allogeneic hematopoietic cell transplant.
AB  - Respiratory viral infections cause significant morbidity and increase the risk
      for chronic pulmonary graft-versus-host disease (GVHD) after hematopoietic cell
      transplantation (HCT). Our overall hypothesis is that local innate immune
      activation potentiates adaptive alloimmunity. In this study, we hypothesized that
      a viral pathogen-associated molecular pattern (PAMP) alone can potentiate
      pulmonary GVHD after allogeneic HCT. We, therefore, examined the effect of
      pulmonary exposure to polyinosinic:polycytidylic acid (poly I:C), a viral mimetic
      that activates innate immunity, in an established murine HCT model. Poly I:C
      induced a marked pulmonary T cell response in allogeneic HCT mice as compared to
      syngeneic HCT, with increased CD4+ cells in the lung fluid and tissue. This
      lymphocytic inflammation persisted at 2 weeks post poly I:C exposure in
      allogeneic mice and was associated with CD3+ cell infiltration into the
      bronchiolar epithelium and features of epithelial injury. In vitro, poly I:C
      enhanced allospecific proliferation in a mixed lymphocyte reaction. In vivo, poly
      I:C exposure was associated with an early increase in pulmonary monocyte
      recruitment and activation as well as a decrease in CD4+FOXP3+ regulatory T cells
      in allogeneic mice as compared to syngeneic. In contrast, intrapulmonary poly I:C
      did not alter the extent of systemic GVHD in either syngeneic or allogeneic mice.
      Collectively, our results suggest that local activation of pulmonary innate
      immunity by a viral molecular pattern represents a novel pathway that contributes
      to pulmonary GVHD after allogeneic HCT, through a mechanism that includes
      increased recruitment and maturation of intrapulmonary monocytes.

PMID- 21070858
TI  - Activation and localization of protein kinase C in Neurospora crassa.
AB  - The Neurosporacrassa protein kinase C (NPKC) is reported to be a regulator of
      light responsive genes. It phosphorylates the light receptor WC-1 and regulates
      the levels of the circadian clock protein FRQ and transcription of the light
      induced albino-2 gene. In mammals, the conventional and novel isoforms of PKC are
      activated by diacylglycerol (DAG), which induces PKC translocation from the
      cytoplasm to membranes. To investigate the interaction of NPKC and DAG in
      Neurospora, we constructed a strain that expresses a PKC-GFP fusion protein. We
      found that NPKC localizes to growing tips and sub-apical plasma membrane in
      actively growing hyphae, and actively participates in septum development. NPKC is
      activated by exogenous DAG and phorbol esters, and translocates to the plasma
      membrane from the cytoplasm. We have previously reported that choline depletion
      of the chol-1 mutant of Neurospora increases DAG levels and lengthens the period
      of the circadian rhythm of conidiation. We have found that the activity of NPKC
      is rhythmic, and that NPKC levels are increased on choline depletion. However,
      over-expression of NPKC did not lengthen the conidiation period, indicating that
      PKC in Neurospora may not be responsible for the lengthened period in low choline
      cultures.

PMID- 21070859
TI  - Genetic identification of unique immunological responses in mice infected with
      virulent and attenuated Francisella tularensis.
AB  - Francisella tularensis is a category A select agent based on its infectivity and
      virulence but disease mechanisms in infection remain poorly understood. Murine
      pulmonary models of infection were therefore employed to assess and compare
      dissemination and pathology and to elucidate the host immune response to
      infection with the highly virulent Type A F. tularensis strain Schu4 versus the
      less virulent Type B live vaccine strain (LVS). We found that dissemination and
      pathology in the spleen was significantly greater in mice infected with F.
      tularensis Schu4 compared to mice infected with F. tularensis LVS. Using gene
      expression profiling to compare the response to infection with the two F.
      tularensis strains, we found that there were significant differences in the
      expression of genes involved in the apoptosis pathway, antigen processing and
      presentation pathways, and inflammatory response pathways in mice infected with
      Schu4 when compared to LVS. These transcriptional differences coincided with
      marked differences in dissemination and severity of organ lesions in mice
      infected with the Schu4 and LVS strains. Therefore, these findings indicate that
      altered apoptosis, antigen presentation and production of inflammatory mediators
      explain the differences in pathogenicity of F. tularensis Schu4 and LVS.

PMID- 21070860
TI  - Brucella abortus inhibits IFN-gamma-induced FcgammaRI expression and FcgammaRI
      restricted phagocytosis via toll-like receptor 2 on human monocytes/macrophages.
AB  - The strategies that allow Brucella abortus to persist for years inside
      macrophages subverting host immune responses are not completely understood.
      Immunity against this bacterium relies on the capacity of IFN-gamma to activate
      macrophages, endowing them with the ability to destroy intracellular bacteria. We
      report here that infection with B. abortus down-modulates the expression of the
      type I receptor for the Fc portion of IgG (FcgammaRI, CD64) and FcgammaRI
      restricted phagocytosis regulated by IFN-gamma in human monocytes/macrophages.
      Both phenomena were not dependent on bacterial viability, since they were also
      induced by heat-killed B. abortus (HKBA), suggesting that they were elicited by a
      structural bacterial component. Accordingly, a prototypical B. abortus
      lipoprotein (L-Omp19), but not its unlipidated form, inhibited both CD64
      expression and FcgammaRI-restricted phagocytosis regulated by IFN-gamma.
      Moreover, a synthetic lipohexapeptide that mimics the structure of the protein
      lipid moiety also inhibited CD64 expression, indicating that any Brucella
      lipoprotein could down-modulate CD64 expression and FcgammaRI-restricted
      phagocytosis. Pre-incubation of monocytes/macrophages with anti-TLR2 mAb blocked
      the inhibition of the CD64 expression mediated by HKBA and L-Omp19. These
      results, together with our previous observations establish that B. abortus
      utilizes its lipoproteins to inhibit the monocytes/macrophages activation
      mediated by IFN-gamma and to subvert host immunonological responses.

PMID- 21070861
TI  - Obligate intracellular bacterium Ehrlichia inhibiting mitochondrial activity.
AB  - Ehrlichia are obligately intracellular bacteria that reside in a vacuole in the
      cytoplasm of phagocytes. We determined by confocal microscopy the interaction
      between Ehrlichia and mitochondria in DH82 cells to investigate the mechanism of
      Ehrlichia survival inside the phagocyte. The most remarkable finding of our study
      was that Ehrlichia morulae interacted with mitochondria and inhibited
      mitochondrial metabolism. We showed that in Ehrlichia chaffeensis-infected DH82
      cells, mitochondria did not incorporate BrdU and transcriptional level of the
      mitochondrial gene NADPH2 was significantly reduced, indicating the inhibition of
      mitochondrial metabolism. This study demonstrates that Ehrlichia are able to
      inhibit mitochondrial activities, and it opens up a new avenue for the study of
      Ehrlichia pathogenesis.

PMID- 21070862
TI  - A synthetic peptide selectively kills only virulent Paracoccidioides brasiliensis
      yeasts.
AB  - This work was conducted to identify virulence biomarkers for Paracoccidioides
      brasiliensis (Pb), the fungus responsible for Paracoccidioidomycosis (PCM), a
      systemic disease endemic in Latin America. Measurement of mortality showed that
      all B10.A mice were killed after 250 days by the virulent Pb18 isolate while only
      one of the mice that received the attenuated counterpart died. Also, number of
      lung CFUs from virulent Pb18 inoculated mice were much higher when these isolates
      were compared. Phage display methodology allowed selection of three phages that
      specifically bound to virulent Pb18. Variability of p04 phage binding to
      different Pb isolates were examples of variability of expression by the fungus of
      its binding molecule, strongly suggesting p04 as a biomarker of virulence. In
      vitro, its derived peptide pep04 killed only virulent fungi, and confocal
      microscopy showed that it was internalized only by the virulent isolate. Pep04
      blocked establishment of Pb infection in mice and virulent Pb18 pre-incubated
      with p04 showed significantly inhibited lung infection. Furthermore, infected
      mice treated with p04 showed highly significant reduction in lung CFUs. These
      findings firmly establish p04 as a biomarker of Pb virulence. Therefore, after
      proper peptide engineering, p04 may become a useful adjuvant for the distressing
      treatment of PCM.

PMID- 21070864
TI  - Identification and characterization of a novel secreted antigen 1 of Babesia
      microti and evaluation of its potential use in enzyme-linked immunosorbent assay
      and immunochromatographic test.
AB  - Here, we identified a novel secreted antigen designated as Babesia microti
      secreted antigen 1 (BmSA1) by immunoscreening a B. microti cDNA expression
      library using the sera from hamsters immunized with plasma, putatively containing
      secreted antigens, from B. microti-infected hamsters. Antibodies raised in mice
      immunized with recombinant BmSA1 (rBmSA1) recognized a native 33-kDa parasite
      protein. An enzyme-linked immunosorbent assay (ELISA) of rBmSA1 detected specific
      antibodies as early as 6 and 4 days post-infection in sera from a hamster
      experimentally infected with B. microti Gray strain (US type) and a mouse
      experimentally infected with B. microti Munich strain (rodent isolate),
      respectively. Moreover, a rapid immunochromatographic test (ICT) using rBmSA1
      detected specific antibodies in a hamster experimentally infected with B. microti
      from day 6 to at least day 270 post-infection, which was quite consistent with
      the results of the ELISA. In addition, analysis of the sera involved in the first
      case of human babesiosis in Japan (Kobe type) showed that specific antibodies
      were detectable in the patient and the positive donor by ELISA using rBmSA1, and
      the ICT result was identical to the ELISA data. Taken together, these results
      indicated that BmSA1 could be a promising and universal target for developing
      both ELISA and ICT for the serodiagnosis of human babesiosis and for an
      epidemiological survey of its rodent reservoir.

PMID- 21070863
TI  - Selective cytotoxicity of Aniba rosaeodora essential oil towards epidermoid
      cancer cells through induction of apoptosis.
AB  - Essential oils are complex mixtures of odorous and volatile compounds derived
      from secondary plant metabolism. They can be isolated from many plants by
      mechanical pressing or hydro- and steam-distillation and are known to induce a
      wide range of biological effects through their antibacterial, antifungal,
      cytotoxic, antioxidant and antimutagenic activities. In order to explore their
      beneficial properties on human skin cells, we investigated the effects of an
      essential oil from rosewood Aniba rosaeodora (REO) on the human epidermoid
      carcinoma cell line A431, on immortal HaCaT cells thought to represent an early
      stage of skin carcinogenesis, on transformed normal HEK001 keratinocytes and on
      primary normal NHEK keratinocytes. In a defined range of concentrations, REO
      selectively killed A431 and HaCaT cells. The same treatments had only a minor
      cytotoxic effect on HEK001 and NHEK cells. Preferentially in A431 and HaCaT
      cells, REO triggered the production of reactive oxygen species, induced
      depolarization of the mitochondrial membrane and caused caspase-dependent cell
      death characterized by phosphatidylserine externalization, an early marker of
      apoptosis. Both intrinsic and extrinsic apoptotic pathways were implicated in REO
      induced cell death. The identification of selective induction of apoptosis in
      precancerous and cancerous skin cells by REO highlights the potential anticancer
      activity of this essential oil.

PMID- 21070865
TI  - Lipid accumulation impairs adiponectin-mediated induction of activin A by
      increasing TGFbeta in primary human hepatocytes.
AB  - Fatty liver is commonly detected in obesity and has been identified as a risk
      factor for the progression of hepatic fibrosis in a wide range of liver diseases.
      Transforming growth factor beta (TGFbeta) and activin A, both members of the
      TGFbeta superfamiliy, are central regulators in liver fibrosis and regeneration,
      and the effect of hepatocyte lipid accumulation on the release of these proteins
      was studied. Primary human hepatocytes (PHH) were incubated with palmitic acid or
      oleic acid to increase lipid storage. Whereas activin A and its natural inhibitor
      follistatin were not affected, TGFbeta was 2-fold increased. The hepatoprotective
      adipokine adiponectin dose-dependently induced activin A while lowering
      follistatin but did not alter TGFbeta. Activin A was markedly reduced in
      hepatocyte cell lines compared to PHH and was not induced upon adiponectin
      incubation demonstrating significant differences of primary and transformed
      cells. In free fatty acid (FFA)-incubated PHH adiponectin-mediated induction of
      activin A was impaired. Inhibition of TGFbeta receptors ALK4/5 and blockage of
      SMAD3 phosphorylation rescued activin A synthesis in FFA and in TGFbeta incubated
      cells suggesting that FFA inhibit adiponectin activity by inducing TGFbeta. To
      evaluate whether serum levels of activin A and its antagonist are altered in
      patients with hepatic steatosis, both proteins were measured in the serum of
      patients with sonographically diagnosed fatty liver and age- and BMI-matched
      controls. Systemic adiponectin was significantly reduced in patients with fatty
      liver but activin A and follistatin were not altered. In summary the current data
      demonstrate that lipid accumulation in hepatocytes induces TGFbeta which impairs
      adiponectin bioactivity, and thereby may contribute to liver injury.

PMID- 21070866
TI  - Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates
      docosahexaenoate metabolizing enzymes in rat brain.
AB  - BACKGROUND: Dietary n-3 polyunsaturated fatty acid (PUFA) deprivation increases
      expression of arachidonic acid (AA 20:4n-6)-selective cytosolic phospholipase
      A(2) (cPLA(2)) IVA and cyclooxygenase (COX)-2 in rat brain, while decreasing
      expression of docosahexaenoic acid (DHA 22:6n-3)-selective calcium-independent
      iPLA(2) VIA. Assuming that these enzyme changes represent brain homeostatic
      responses to deprivation, we hypothesized that dietary n-6 PUFA deprivation would
      produce changes in the opposite directions. METHODS: Brain expression of PUFA
      metabolizing enzymes and their transcription factors was quantified in male rats
      fed an n-6 PUFA adequate or deficient diet for 15weeks post-weaning. RESULTS: The
      deficient compared with adequate diet increased brain mRNA, protein and activity
      of iPLA(2) VIA and 15-lipoxygenase (LOX), but decreased cPLA(2) IVA and COX-2
      expression. The brain protein level of the iPLA(2) transcription factor SREBP-1
      was elevated, while protein levels were decreased for AP-2alpha and NF-kappaB
      p65, cPLA(2) and COX-2 transcription factors, respectively. CONCLUSIONS: With
      dietary n-6 PUFA deprivation, rat brain PUFA metabolizing enzymes and some of
      their transcription factors change in a way that would homeostatically dampen
      reductions in brain n-6 PUFA concentrations and metabolism, while n-3 PUFA
      metabolizing enzyme expression is increased. The changes correspond to reported
      in vitro enzyme selectivities for AA compared with DHA.

PMID- 21070867
TI  - PPARbeta/delta activation blocks lipid-induced inflammatory pathways in mouse
      heart and human cardiac cells.
AB  - Owing to its high fat content, the classical Western diet has a range of adverse
      effects on the heart, including enhanced inflammation, hypertrophy, and
      contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which
      are under the transcriptional control of nuclear factor-kappaB (NF-kappaB), may
      contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms
      are complex, since they are linked to systemic metabolic abnormalities and
      changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors
      (PPARs) are transcription factors that regulate metabolism and are capable of
      limiting myocardial inflammation and hypertrophy via inhibition of NF-kappaB.
      Since PPARbeta/delta is the most prevalent PPAR isoform in the heart, we analyzed
      the effects of the PPARbeta/delta agonist GW501516 on inflammatory parameters. A
      high-fat diet induced the expression of tumor necrosis factor-alpha, monocyte
      chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF
      kappaB in the heart of mice. GW501516 abrogated this enhanced proinflammatory
      profile. Similar results were obtained when human cardiac AC16 cells exposed to
      palmitate were coincubated with GW501516. PPARbeta/delta activation by GW501516
      enhanced the physical interaction between PPARbeta/delta and p65, which suggests
      that this mechanism may also interfere NF-kappaB transactivation capacity in the
      heart. GW501516-induced PPARbeta/delta activation can attenuate the inflammatory
      response induced in human cardiac AC16 cells exposed to the saturated fatty acid
      palmitate and in mice fed a high-fat diet. This is relevant, especially taking
      into account that PPARbeta/delta has been postulated as a potential target in the
      treatment of obesity and the insulin resistance state.

PMID- 21070868
TI  - GABA inhibition of luminescence from lantern shark (Etmopterus spinax)
      photophores.
AB  - Photogenic organs (photophores) of the velvet belly lantern shark (Etmopterus
      spinax) are under hormonal control, since melatonin (MT) and prolactin (PRL)
      trigger luminescence while alpha-melanocyte-stimulating hormone (alpha-MSH)
      prevents this light to be emitted. A recent study supported, however, the
      presence of numerous nerve fibres in the photogenic tissue of this shark.
      Immunohistochemical and pharmacological results collected in this work support
      these nerve fibres to be inhibitory GABAergic nerves since (i) GABA
      immunoreactivity was detected inside the photogenic tissue, where previous
      labelling detected the nerve fibre structures and (ii) GABA was able to inhibit
      MT and PRL-induced luminescence, which was on the other hand increased by the
      GABA(A) antagonist bicuculline (BICU). In addition, we also demonstrated that
      BICU can induce light per se by provoking pigment retraction in the pigmented
      cells composing the iris-like structure of the photophore, attaining, however,
      only about 10% of hormonally induced luminescence intensity at 10(-3)mol L(-1).
      This strongly supports that a GABA inhibitory tonus controls photophore
      "aperture" in the photogenic tissue of E. spinax but also that MT and PRL have
      more than one target cell type in the photophores.

PMID- 21070869
TI  - Ascites caused by arterioportal fistula 15 years after liver biopsy.

PMID- 21070870
TI  - Hookworm infection detected by capsule endoscopy in a young man with iron
      deficiency.

PMID- 21070871
TI  - Adenocarcinoma revealing ileal Crohn's disease.

PMID- 21070872
TI  - Rapid development of colorectal neoplasia in patients with Lynch syndrome.
AB  - BACKGROUND & AIMS: Patients with Lynch syndrome have a high risk for colorectal
      adenomas and carcinomas. We evaluated the development of colorectal neoplasia in
      these patients. METHODS: We assessed serial colonoscopy findings from 54 persons
      from 29 pedigrees with pathogenic mutations in MSH2 or MLH1; we evaluated the
      development of colorectal neoplasia by age, sex, tumor location, and number (mean
      follow-up time, 9.3 years; colonoscopy interval, 1.7 +/- 1.2 years; 112 adenomas
      and 31 cancers). Differences in colorectal phenotype were analyzed by genotype,
      and dwell time was calculated for advanced neoplasias. RESULTS: Among mutation
      carriers, the cumulative risk of colorectal neoplasia was 43% by age 40 years and
      72% by 80 years. There were no statistically significant associations between
      time to development of colorectal neoplasia and sex or mutation type. Most female
      patients had left-sided neoplasms, whereas most male patients developed right
      sided lesions. The mean cumulative numbers of neoplastic lesions in patients were
      1.3 +/- 0.5 by age 30 years and 7.6 +/- 6.8 by age 80 years. Polyp dwell time was
      33.0 +/- 16.2 months and 35.2 +/- 22.3 months for advanced adenoma and colorectal
      cancer, respectively. The 5-year survival rate for patients with colorectal
      cancer was 96%. CONCLUSIONS: High percentages of individuals with pathogenic
      mutations in MSH2 or MLH1 develop colorectal neoplasia by age 40. Left-sided
      colorectal neoplasias are more frequent in female patients. The development of 3
      or more colorectal neoplasms by age 30 years indicates a possible polyposis
      syndrome rather than Lynch syndrome. Polyp dwell time is short for advanced
      neoplasias, arguing for annual colonoscopic screening and surveillance.

PMID- 21070873
TI  - What is driving the legal interest in hepatic encephalopathy?

PMID- 21070874
TI  - Eosinophilic esophagitis and gastroesophageal reflux disease: there and back
      again.

PMID- 21070875
TI  - Colocolonic intussusception with a leading point.

PMID- 21070876
TI  - Endoscopy in microstomia: thinking outside the box.

PMID- 21070877
TI  - Primary esophageal B-cell lymphoma.

PMID- 21070878
TI  - Complete resolution of emphysematous gastritis after conservative management.

PMID- 21070879
TI  - Percutaneous liver biopsy.

PMID- 21070880
TI  - Heart rate and rhythm benefits from bariatric surgery, weight loss, and
      associated matters: another autonomic tale.

PMID- 21070881
TI  - Entrainment of supraventricular tachycardia: what is the mechanism?

PMID- 21070882
TI  - Prospective, population-based long QT molecular autopsy study of postmortem
      negative sudden death in 1 to 40 year olds.
AB  - BACKGROUND: Retrospective investigation of sudden unexplained death in the young
      (SUDY) reveals that a high proportion is due to inherited heart disease.
      OBJECTIVE: The purpose of this study was to ascertain the diagnostic value of
      postmortem long QT (LQT) genetic analysis in a prospective study of SUDY victims
      1-40 years old. METHODS: Denaturing high-performance liquid chromatography or
      direct sequencing of LQT genes 1, 2, 3, 5, and 6 was performed, in a National New
      Zealand protocol, in SUDY victims aged 1-40 years. RESULTS: Over 26 months (2006
      2008), DNA was stored at autopsy from 52 victims of sudden unexpected death.
      Further testing revealed a diagnosis in 19 cases (poisoning 4, dilated
      cardiomyopathy 3, myocarditis 3, other 9). The remaining 33 cases underwent
      genetic testing (age at death 18 months-40 years, median 25 years). Eighteen
      (55%) died during sleep or at rest, and 7 (21%) died during light activity. Rare
      missense variants in LQT genes were found in 5 (15%) cases (confidence interval
      3%-27%): T96R in KCNQ1 (11-year-old male), P968L in KCNH2 (32-year-old female),
      P2006A in SCN5A (34-year-old female), and R67H and R98W in KCNE1 (17- and 38-year
      old females, respectively). Evidence of pathogenicity was provided by in vitro
      evidence (T96R), family phenotype-genotype co-segregation (R98W, P2006A), and/or
      previous reports (R67H, P968L, P2006A, R98W). Family cardiac investigation was
      possible in 23 (70%) families and revealed probable cause of death for 5 (15%)
      other victims (confidence interval 3%-27%). CONCLUSION: Most community SUDY
      occurs at rest or during light activity. A diagnostic rate of 15% supports the
      transition of LQT genetic autopsy, combined with family investigation, into
      routine medical practice.

PMID- 21070883
TI  - Intermittent atrioventricular block: what is the mechanism?

PMID- 21070884
TI  - Retrograde placement of a defibrillator lead through the pulmonary valve.

PMID- 21070885
TI  - Safety and reliability of the insertable Reveal XT recorder in patients
      undergoing 3 Tesla brain magnetic resonance imaging.
AB  - BACKGROUND: Up to now there is little evidence about the safety and reliability
      of insertable cardiac monitors (ICMs) in patients undergoing magnetic resonance
      imaging (MRI). OBJECTIVE: The purpose of this prospective single-center study
      (MACPAF; clinicaltrials.govNCT01061931), which we are currently performing, was
      to evaluate these issues for the ICM Reveal XT at a 3 Tesla MRI scanner in
      patients undergoing serial brain MRI. METHODS: We present an interim analysis
      including 62 brain MRI examinations in 24 patients with paroxysmal atrial
      fibrillation bearing the Reveal XT. All patients were interviewed for potential
      ICM-associated clinical symptoms during and after MRI examination. According to
      the study protocol, data from the Reveal XT were transmitted before and after the
      MRI examination. RESULTS: All patients were clinically asymptomatic during the
      MRI procedure. Moreover, the reliability (ability to detect signals, battery
      status) of the Reveal XT was unaffected, except for one MRI-induced artifact that
      was recorded by the ICM, mimicking a narrow complex tachycardia, as similarly
      recorded in a further study patient bearing the forerunner ICM Reveal DX. No loss
      of ICM data was observed after the MRI examination. CONCLUSIONS: The 3 Tesla
      brain MRI scanning is safe for patients bearing the ICM Reveal XT and does not
      alloy reliability of the Reveal XT itself. MRI-induced artifacts occur rarely but
      have to be taken into account.

PMID- 21070886
TI  - Differential outcome of cardiac resynchronization therapy in ischemic
      cardiomyopathy and idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is a therapy of proven
      benefit in patients with advanced heart failure. Identifying potential responders
      remains challenging, and whether the etiology of the heart failure is related to
      the potential hemodynamic benefit and long-term outcome of CRT is unclear.
      OBJECTIVE: The purpose of this study was to evaluate whether heart failure
      etiology (ischemic cardiomyopathy [ICM] vs nonischemic dilated cardiomyopathy
      [DCM]) was associated with CRT outcome and implantable cardioverter-defibrillator
      (ICD) shocks. METHODS: The study included 503 CRT recipients (CRT-D 90%) in a
      longitudinal CRT database: ICM (n = 312) and DCM (n = 191). Clinical variables
      and echocardiographic measures preimplant and postimplant were collected.
      Actuarial survival and ICD therapy data were assessed with Kaplan-Meier curve and
      log rank tests. RESULTS: Pre-CRT, ICM patients were older and had higher
      creatinine levels (P <.001). At median follow-up of 7.1 months, the DCM group
      experienced greater improvement in left ventricular ejection fraction (8.3% +/-
      10% vs 6.2% +/- 10%, P = .05) and left ventricular end-diastolic volumes than did
      those with ICM (-28%.4 +/- 53 mL vs -15.3 +/- 46 mL, P = .024). Survival
      estimates at 4 years were 55% for ICM and 77% for DCM groups (P <.001),
      respectively, whereas no significant difference in the incidence of
      appropriate/inappropriate ICD shocks was observed. The ICM group remained at
      higher risk for death compared to the DCM group after controlling for preimplant
      variables (hazard ratio 1.6, 95% confidence interval 1.1-2.3, P = .008).
      CONCLUSION: In response to CRT and in contrast to ICM, DCM patients experienced
      greater improvement in left ventricular systolic function and reverse remodeling
      while also sustaining a greater survival benefit.

PMID- 21070887
TI  - A broad complex tachycardia: what is the mechanism?

PMID- 21070888
TI  - Cancer targeting potential of some ligand-anchored poly(propylene imine)
      dendrimers: a comparison.
AB  - The present investigation was aimed at developing and comparing the cancer
      targeting potential of ligand-anchored dendrimers. Folate-, dextran-, and
      galactose-anchored poly(propylene imine) dendrimers were synthesized and
      characterized. Dendritic formulations were evaluated for ex vivo cytotoxicity on
      HeLa and SiHa cell lines. Flow cytometry studies were performed on the HeLa cell
      line. An ex vivo MTT assay on HeLa cells indicated IC(50) values of 0.05, 0.2,
      0.8, and 0.08 MUM for folate, dextran, and galactose formulations, and for free
      paclitaxel (PTX), respectively. An analogous observation was carried out in SiHa
      cells, where IC(50) values of 0.6, 0.8, 10, and 6 MUM were observed by folate,
      dextran, and galactose formulations, and free PTX, respectively. The outcome of
      the MTT assay and flow cytometry suggested the order of targeting potential of
      various ligands under investigation as folate > dextran > galactose. The outcome
      is deemed to be of scientific value and is believed to assist drug delivery
      scientists during selection of targeting ligands. FROM THE CLINICAL EDITOR: The
      cancer targeting potential of folate, dextran and galactose functionalized
      polypropyleneimine (PPI) dendrimers was studied by this group of investigators,
      reporting the order of targeting potential as folate > dextran > galactose.

PMID- 21070889
TI  - Comparison of intraclass correlation coefficient estimates and standard errors
      between using cross-sectional and repeated measurement data: the Safety Check
      cluster randomized trial.
AB  - Designing cluster randomized trials in clinical studies often requires accurate
      estimates of intraclass correlation, which quantifies the strength of correlation
      between units, such as participants, within a cluster, such as a practice.
      Published ICC estimates, even when available, often suffer from the problem of
      wide confidence intervals. Using data from a national, randomized, controlled
      study concerning violence prevention for children--the Safety Check--we compare
      the ICC values derived from two approaches only baseline data and using both
      baseline and follow-up data. Using a variance component decomposition approach,
      the latter method allows flexibility in handling complex data sets. For example,
      it allows for shifts in the outcome variable over time and for an unbalanced
      cluster design. Furthermore, we evaluate the large-sample formula for ICC
      estimates and standard errors using the bootstrap method. Our findings suggest
      that ICC estimates range from 0.012 to 0.11 for providers within practice and
      range from 0.018 to 0.11 for families within provider. The estimates derived from
      the baseline-only and repeated-measurements approaches agree quite well except in
      cases in which variation over repeated measurements is large. The reductions in
      the widths of ICC confidence limits from using repeated measurement over baseline
      only are, respectively, 62% and 42% at the practice and provider levels. The
      contribution of this paper therefore includes two elements, which are a
      methodology for improving the accuracy of ICC, and the reporting of such
      quantities for pediatric and other researchers who are interested in designing
      clustered randomized trials similar to the current study.

PMID- 21070890
TI  - The blind leading the blind: use and misuse of blinding in randomized controlled
      trials.
AB  - The use of blinding strengthens the credibility of randomized controlled trials
      (RCTs) by minimizing bias. However, there is confusion surrounding the definition
      of blinding as well as the terms single, double, and triple blind. It has been
      suggested that these terms should be discontinued due to their broad
      misinterpretation. We recommend that, instead of abandoning the use of these
      terms, explicit definitions of blinding should be adopted. We address herein the
      concept of blinding, propose standard definitions for the consistent use of these
      terms, and detail when different types of blinding should be utilized.
      Standardizing the definition of blinding and utilizing proper blinding methods
      will improve the quality and clarity of reporting in RCTs.

PMID- 21070891
TI  - Heritability and adaptive phenotypic plasticity of adult body size in the
      mosquito Aedes aegypti with implications for dengue vector competence.
AB  - Adaptive phenotypic plasticity is particularly important to organisms with
      developmental cycles that undergo ontogenetic niche shifts that differentially
      subject individual life stages to heterogeneous and often stressful environmental
      conditions. The yellow fever and dengue fever vector mosquito, Aedes aegypti,
      typically breeds in small water-filled containers that expose the developing
      aquatic larvae to competition for resources with conspecifics and high
      probabilities for habitat drying. Here we investigated the heritability (h(2))
      and phenotypic plasticity among A. aegypti laboratory populations and field
      populations from Trinidad, West Indies. Heritability for body size was moderate
      or completely eroded among the laboratory populations, while field populations
      contained high genetic variation among both males and females. Norms of reactions
      based on optimum vs. deficient larval conditions for artificial sibling families
      representing Trinidad field populations suggested significant gene * environment
      interactions influence body size and that there may be sex specific differences
      in allocation of resources. Individuals reared under optimum laboratory
      conditions were significantly larger and showed much less variability in body
      size plasticity than their field reared cohorts, suggesting that exposure to
      environmental stress may be common for A. aegypti larval development and would
      undoubtedly impact other traits, including arbovirus vector competence among
      adult females, in a similar fashion. Broad genetic variance in body size and
      other characters is likely maintained by balancing selection. Our results also
      suggest the need for caution in translating conclusions from experiments with
      laboratory colonies to natural populations. These would likely be more
      informative to expected phenotypes under natural conditions if conducted over a
      range of conditions that simulate environmental stress.

PMID- 21070892
TI  - Non-invasive system for applying airway obstructions to model obstructive sleep
      apnea in mice.
AB  - Obstructive sleep apnea (OSA) is characterized by recurrent upper airway
      obstructions during sleep. The most common animal model of OSA is based on
      subjecting rodents to intermittent hypoxic exposures and does not mimic important
      OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To
      circumvent some of these issues, a novel murine model involving non-invasive
      application of recurrent airway obstructions was developed. An electronically
      controlled airbag system is placed in front of the mouse's snout, whereby
      inflating the airbag leads to obstructed breathing and spontaneous breathing
      occurs with the airbag deflated. The device was tested on 29 anesthetized mice by
      measuring inspiratory effort and arterial oxygen saturation (SaO2). Application
      of recurrent obstructive apneas (6 s each, 120/h) for 6h resulted in SaO2
      oscillations to values reaching 84.4 +/- 2.5% nadir, with swings mimicking OSA
      patients. This novel system, capable of applying controlled recurrent airway
      obstructions in mice, is an easy-to-use tool for investigating pertinent aspects
      of OSA.

PMID- 21070893
TI  - Structural characterization of a group II 2/2 hemoglobin from the plant pathogen
      Agrobacterium tumefaciens.
AB  - Within the 2/2 hemoglobin sub-family, no group II 2/2Hbs from proteobacteria have
      been so far studied. Here we present the first structural characterization of a
      group II 2/2Hb from the soil and phytopathogenic bacterium Agrobacterium
      tumefaciens (At-2/2HbO). The crystal structure of ferric At-2/2HbO (reported at
      2.1A resolution) shows the location of specific/unique heme distal site residues
      (e.g., His(42)CD1, a residue distinctive of proteobacteria group II 2/2Hbs) that
      surround a heme-liganded water molecule. A highly intertwined hydrogen-bonded
      network, involving residues Tyr(26)B10, His(42)CD1, Ser(49)E7, Trp(93)G8, and
      three distal site water molecules, stabilizes the heme-bound ligand. Such a
      structural organization suggests a path for diatomic ligand diffusion to/from the
      heme. Neither a similar distal site structuring effect nor the presence of distal
      site water molecules has been so far observed in group I and group III 2/2Hbs,
      thus adding new distinctive information to the complex picture of currently
      available 2/2Hb structural and functional data. This article is part of a Special
      Issue entitled: Protein Structure and Function in the Crystalline State.

PMID- 21070894
TI  - An analysis of the Caenorhabditis elegans lipid raft proteome using geLC-MS/MS.
AB  - Lipid rafts are microdomains of the phospholipid bilayer, proposed to form semi
      stable "islands" that act as a platform for several important cellular processes;
      major classes of raft-resident proteins include signalling proteins and
      glycosylphosphatidylinositol (GPI)-anchored proteins. Proteomic studies into
      lipid rafts have been mainly carried out in mammalian cell lines and single cell
      organisms. The nematode Caenorhabditis elegans, the model organism with a well
      defined developmental profile, is ideally suited for the study of this
      subcellular locale in a complex developmental context. A study of the lipid raft
      proteome of C. elegans is presented here. A total of 44 proteins were identified
      from the lipid raft fraction using geLC-MS/MS, of which 40 have been determined
      to be likely raft proteins after analysis of predicted functions. Prediction of
      GPI-anchoring of the proteins found 21 to be potentially modified in this way,
      two of which were experimentally confirmed to be GPI-anchored. This work is the
      first reported study of the lipid raft proteome in C. elegans. The results show
      that raft proteins, including numerous GPI-anchored proteins, may have a variety
      of potentially important roles within the nematode, and will hopefully lead to C.
      elegans becoming a useful model for the study of lipid rafts.

PMID- 21070896
TI  - Extending rare-variant testing strategies: analysis of noncoding sequence and
      imputed genotypes.
AB  - Next Generation Sequencing Technology has revolutionized our ability to study the
      contribution of rare genetic variation to heritable traits. However, existing
      single-marker association tests are underpowered for detecting rare risk
      variants. A more powerful approach involves pooling methods that combine multiple
      rare variants from the same gene into a single test statistic. Proposed pooling
      methods can be limited because they generally assume high-quality genotypes
      derived from deep-coverage sequencing, which may not be available. In this paper,
      we consider an intuitive and computationally efficient pooling statistic, the
      cumulative minor-allele test (CMAT). We assess the performance of the CMAT and
      other pooling methods on datasets simulated with population genetic models to
      contain realistic levels of neutral variation. We consider study designs ranging
      from exon-only to whole-gene analyses that contain noncoding variants. For all
      study designs, the CMAT achieves power comparable to that of previously proposed
      methods. We then extend the CMAT to probabilistic genotypes and describe
      application to low-coverage sequencing and imputation data. We show that
      augmenting sequence data with imputed samples is a practical method for
      increasing the power of rare-variant studies. We also provide a method of
      controlling for confounding variables such as population stratification. Finally,
      we demonstrate that our method makes it possible to use external imputation
      templates to analyze rare variants imputed into existing GWAS datasets. As proof
      of principle, we performed a CMAT analysis of more than 8 million SNPs that we
      imputed into the GAIN psoriasis dataset by using haplotypes from the 1000 Genomes
      Project.

PMID- 21070898
TI  - Flat colon polyps: what should radiologists know?
AB  - With the recent publication of international computed tomography (CT)
      colonography standards, which aim to improve quality of examinations, this review
      informs radiologists about the significance of flat polyps (adenomas and
      hyperplastic polyps) in colorectal cancer pathways. We describe flat polyp
      classification systems and propose how flat polyps should be reported to ensure
      patient management strategies are based on polyp morphology as well as size.
      Indeed, consistency when describing flat polyps is of increasing importance given
      the strengthening links between CT colonography and endoscopy.

PMID- 21070897
TI  - Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa.
AB  - The study of inherited retinal diseases has advanced our knowledge of the
      cellular and molecular mechanisms involved in sensory neural signaling.
      Dysfunction of two specific sensory modalities, vision and proprioception,
      characterizes the phenotype of the rare, autosomal-recessive disorder posterior
      column ataxia and retinitis pigmentosa (PCARP). Using targeted DNA capture and
      high-throughput sequencing, we analyzed the entire 4.2 Mb candidate sequence on
      chromosome 1q32 to find the gene mutated in PCARP in a single family. Employing
      comprehensive bioinformatic analysis and filtering, we identified a single
      nucleotide coding variant in the feline leukemia virus subgroup C cellular
      receptor 1 (FLVCR1), a gene encoding a heme-transporter protein. Sanger
      sequencing confirmed the FLVCR1 mutation in this family and identified different
      homozygous missense mutations located within the protein's transmembrane channel
      segment in two other unrelated families with PCARP. To determine whether the
      selective pathologic features of PCARP correlated with FLVCR1 expression, we
      examined wild-type mouse Flvcr1 mRNA levels in the posterior column of the spinal
      cord and the retina via quantitative real-time reverse-transcriptase PCR. The
      Flvcr1 mRNA levels were most abundant in the retina, followed by the posterior
      column of the spinal cord and other brain regions. These results suggest that
      aberrant FLVCR1 causes a selective degeneration of a subpopulation of neurons in
      the retina and the posterior columns of the spinal cord via dysregulation of heme
      or iron homeostasis. This finding broadens the molecular basis of sensory neural
      signaling to include common mechanisms that involve proprioception and vision.

PMID- 21070899
TI  - Fraudulent retouching of digital radiographic images--a potential risk.
AB  - AIM: To determine whether radiologists can recognize images retouched to include
      sham lesions. MATERIALS AND METHODS: Ten representative key images were selected
      of aortic dissection, hepatocellular carcinoma, renal cell carcinoma, colon
      cancer, liver metastasis, hepatic cyst, gallbladder stones, splenic artery
      aneurysm, adrenal adenoma, and stomach cancer from abdominal computed tomography
      (CT) imaging performed in 2008. Five of the key images were replaced with
      retouched images using image-editing software. The time to complete retouching
      was recorded for each image. Radiologists were requested to make a diagnosis for
      the 10 images, and were then asked to identify possible retouched images. The
      time taken to reach a decision in each case was recorded. Thirty radiologists (13
      residents and 17 attending radiologists) participated as reviewers. RESULTS: The
      time to complete retouching was 15.2+/-3.15 min. None of the reviewers recognized
      that some images were retouched during diagnosis. The rate of correct diagnosis
      was 90% (range 71.7-100%). After reviewers were informed of possible image
      retouching, the detection rate of retouched images was 50% (40-58.3%). This rate
      was statistically the same as random choice (p=0.876). There was no significant
      difference between residents and attending radiologists in the detection rate of
      retouched images (p=0.786). The time to diagnosis and the time to detection of
      the retouched images were 15 (14-17) and 6 (5-7) min, respectively. CONCLUSION:
      Digital images can be easily retouched, and radiologists have difficulty in
      identifying retouched images. Radiologists should be aware of the potential
      fraudulent use of retouched images.

PMID- 21070900
TI  - The MRI appearances of early vertebral osteomyelitis and discitis.
AB  - AIM: To describe the magnetic resonance imaging (MRI) appearances in patients
      with a clinical history suggestive of vertebral osteomyelitis and discitis who
      underwent MRI very early in their clinical course. MATERIALS AND METHODS: A
      retrospective review of the database of spinal infections from a spinal
      microbiological liaison team was performed over a 2 year period to identify cases
      with clinical features suggestive of spinal infection and an MRI that did not
      show features typical of vertebral osteomyelitis and discitis. All patients had
      positive microbiology and a follow up MRI showing typical features of spinal
      infection. RESULTS: In four cases the features typical of spinal infection were
      not evident at the initial MRI. In three cases there was very subtle endplate
      oedema associated with disc degeneration, which was interpreted as Modic type I
      degenerative endplate change. Intravenous antibiotic therapy was continued prior
      to repeat MRI examinations. The mean time to the repeat examination was 17 days
      with a range of 8-22 days. The second examinations clearly demonstrated vertebral
      osteomyelitis and discitis. CONCLUSION: Although MRI is the imaging method of
      choice for vertebral osteomyelitis and discitis in the early stages, it may show
      subtle, non-specific endplate subchondral changes; a repeat examination may be
      required to show the typical features.

PMID- 21070901
TI  - Commentary on the MRI appearances of early osteomyelitis and discitis.

PMID- 21070902
TI  - IRMER regulations: compliance rate of radiograph reporting by non-radiology
      clinicians.
AB  - AIM: To assess compliance with regulation 7(8) of Ionizing Radiation Medical
      Exposure Regulations (IRMER) 2000 legislation amongst non-radiologists reporting
      radiographs in a large district general hospital. MATERIALS AND METHODS: A
      prospective review of 100 consecutive radiography request cards from five
      different departments undertaking their specialty radiograph reporting were
      collected over 4 weeks. The requests were then traced to their respective case
      notes to assess documentation of radiographs. The five departments included
      chest, maxillo-facial, rheumatology, orthopaedics, and inpatients. Twenty-two
      case notes were gathered from chest clinics, 21 from maxillo-facial, 15 from
      rheumatology, 23 from orthopaedics fracture clinics, and 19 were taken from
      inpatients. RESULTS: Only 53% of radiographs undertaken by non-radiologists had a
      documented report. The specialty most compliant with IRMER was orthopaedics 17/23
      (74%) and the specialty least compliant was maxilla-facial 8/21 (38%). Of the
      documented radiographs, the consultant grade was the largest group of doctors
      [36% (19/53)] that undertook documentation, and for the undocumented radiographs,
      they were also the largest group of clinicians that did not document radiographs
      [77% (36/47)]. All radiographs that were documented in the notes also had
      documented interpretation of the radiograph. CONCLUSION: Only 53% of plain
      radiographs were documented and reported by non-radiology clinicians even though
      IRMER legislation applies to all clinicians undertaking radiograph
      interpretation. All clinicians undertaking interpretation of radiographs should
      be made aware of this legislation and the responsibility to document their
      findings.

PMID- 21070903
TI  - Comparative study of whole-body MRI and bone scintigraphy for the detection of
      bone metastases.
AB  - AIM: To assess and compare the diagnostic accuracy of whole-body magnetic
      resonance imaging (MRI) and bone scintigraphy in the detection of metastases to
      bone. MATERIAL AND METHODS: Forty randomly selected patients with known malignant
      tumours were prospectively studied using bone scintigraphy and whole-body MRI.
      Two patients were excluded. Symptoms of bone metastasis were present in 29 (76%)
      patients and absent in nine (24%). Findings were classified into four categories
      according to the probability of bone metastasis: (1) negative, (2) probably
      negative, (3) probably positive, and (4) positive. Diagnostic accuracy was
      determined according to the area under the receiver operating characteristic
      (ROC) curve. The definitive diagnosis was reached using other imaging techniques,
      biopsy, or 12 months clinical follow-up. RESULTS: Metastases were present in 18
      patients. The sensitivity, specificity, and diagnostic accuracy were 94, 90, and
      92%, respectively, for whole-body MRI and 72, 75, and 74%, respectively, for bone
      scintigraphy. Diagnostic accuracy measured by the area under the ROC curve was
      significantly higher for whole-body MRI (96%) than for bone scintigraphy (77%;
      p<0.05). Interobserver agreement measured by the kappa index was significantly
      higher for whole-body MRI (0.895) than for bone scintigraphy (0.524; p<0.05).
      Whole-body MRI detected lesions in tissues other than bone in 17 (45%) patients.
      CONCLUSIONS: Whole-body MRI is more accurate and more objective than bone
      scintigraphy for the detection of bone metastases. Whole-body MRI can also detect
      lesions in tissues other than bone.

PMID- 21070904
TI  - CT colonography training for radiographers--a formal evaluation.
AB  - AIMS: To evaluate the efficacy of a new intensive "hands-on" course designed to
      train small teams of radiographers in computed tomography colonography (CTC)
      technique and initial interpretation for patient triage. MATERIALS AND METHODS:
      The course comprised small-group lectures, active participation in the daily CTC
      service with practical technique and image interpretation training by experienced
      radiologists and radiographers. Evaluation was by assessment of knowledge using
      randomized sets of multiple choice questions (MCQ; pre/post-course), practical
      technique using checklists and expert global scores, and interpretation
      performance outcomes using randomized pre/post-course test datasets (five
      validated CTC examinations each). Paired t-tests were used to investigate change
      in performance for MCQ score and interpretation accuracy. RESULTS: Thirteen
      courses with 49 participants were evaluated over 2 years. Practical skills were
      high, with mean (SD) checklist scores of 14/15 (0.85) and global scores of 26/30
      (2.3). MCQ scores increased significantly from a mean of 59% pre-course to 69%
      post-course, p<0.001. Correct classification of CTC examination improved
      significantly from a mean of 55% pre-course to 71% post-course, p<0.001. Cancer
      and large polyp (>10mm) detection rates also improved significantly from 49% to
      60%, p=0.002. CONCLUSION: Structured training in CTC can significantly improve
      knowledge and interpretation skills of radiographers, while assessing safe
      procedural performance. Implementation of similar programmes nationally may help
      reduce performance gaps between centres.

PMID- 21070905
TI  - Diffusion-weighted imaging in breast cancer: relationship between apparent
      diffusion coefficient and tumour aggressiveness.
AB  - AIM: To assess the utility of diffusion-weighted imaging in diagnosing and
      characterizing breast malignancy. MATERIALS AND METHODS: From April 2006 to April
      2009, all consecutive patients with breast cancer undergoing breast magnetic
      resonance imaging (MRI) and subsequent surgery in our hospital were enrolled in
      this study. MRI was performed using a 1.5 T MRI unit using a dedicated,
      bilateral, four-channel breast coil. The MRI protocol included a diffusion
      sequence acquired using b values of 0 and 1000 s/mm(2). For each malignant lesion
      the relationships between tumour grade and histology and the relative value of
      the apparent diffusion coefficient (ADC) were analysed. RESULTS: There were 136
      female patients with 162 lesions. Histology revealed 149 invasive carcinomas and
      13 ductal carcinomas in situ. There were 34 grade 1, 61 grade 2, and 67 grade 3
      lesions. The mean ADC value of all malignant lesions was 1.03*10(-3) mm(2)/s. The
      mean ADC values for invasive and in situ carcinomas were 1.03*10(-3) mm(2)/s and
      1.05*10(-3) mm(2)/s, respectively. The mean ADC values for grade 1, 2, and 3
      tumours were 1.25*10(-3) mm(2)/s, 1.02*10(-3) mm(2)/s, and 0.92*10(-3) mm(2)/s,
      respectively. A statistically significant (p<0.001) inverse correlation was
      disclosed between the ADC value and the tumour grading. The mean ADC value of the
      "less aggressive" group of disease (G1 and in situ lesions) was 1.19*10(-3)
      mm(2)/s, whereas the mean ADC value of the "more aggressive" group (G2-G3
      invasive carcinomas) was 0.96*10(-3) mm(2)/s (p<0.001). CONCLUSION: The study
      confirms the usefulness of diffusion imaging in assessing the aggressiveness of
      breast tumours. ADC appears to be a promising parameter in the evaluation of the
      degree of malignancy of breast cancer tissue.

PMID- 21070906
TI  - Cardiac CT: are we underestimating the dose? A radiation dose study utilizing the
      2007 ICRP tissue weighting factors and a cardiac specific scan volume.
AB  - AIM: To calculate the effective dose from cardiac multidetector computed
      tomography (MDCT) using a computer-based model utilizing the latest International
      Commission on Radiation Protection (ICRP) 103 tissue-weighting factors (2007), to
      compare this dose with those calculated with previously published chest
      conversion factors and to produce a conversion factor specific for cardiac MDCT.
      MATERIALS AND METHODS: An observational study of 152 patients attending for
      cardiac MDCT as part of their usual clinical care in a university teaching
      hospital. The dose for each examination was calculated using the computer-based
      anthropomorphic ImPACT model (the imaging performance assessment of CT scanners)
      and this was compared with the dose derived from the dose-length product (DLP)
      and a chest conversion factor. RESULTS: The median effective dose calculated
      using the ImPACT calculator (4.5 mSv) was significantly higher than the doses
      calculated with the chest conversion factors (2.2-3 mSv). CONCLUSION: The use of
      chest conversion factors significantly underestimates the effective dose when
      compared to the dose calculated using the ImPACT calculator. A conversion factor
      of 0.028 would give a better estimation of the effective dose from prospectively
      gated cardiac MDCT.

PMID- 21070907
TI  - Retrieval of a fractured drill tip during osteoid osteoma treatment.

PMID- 21070908
TI  - Imaging of illicit drug use.
AB  - Illicit drug abuse is a continuing menace of epidemic proportions associated with
      serious medical and social problems. Drug abuse can have a wide variety of
      presentations some of which can be life-threatening. The clinical diagnosis can
      be challenging as the history is usually limited or absent. Radiologists need to
      be familiar with varied imaging presentations and the related complications of
      illicit drug abuse to ensure correct diagnosis and appropriate timely treatment.
      This review will illustrate the imaging spectrum of illicit drug abuse involving
      several organ systems and also discuss the pathophysiological consequences of
      drug abuse.

PMID- 21070909
TI  - Imaging malignant and apparent malignant transformation of benign gynaecological
      disease.
AB  - Common benign gynaecological diseases, such as leiomyoma, adenomyosis,
      endometriosis, and mature teratoma, rarely undergo malignant transformation.
      Benign transformations that may mimic malignancy include benign metastasizing
      leiomyoma, massive ovarian oedema, decidualization of endometrioma, and rupture
      of mature teratoma. The aim of this review is to provide a contemporary overview
      of imaging findings in malignant and apparent malignant transformation of benign
      gynaecological disease.

PMID- 21070910
TI  - An unusual arterial supply to the uterus. A case report and review of anatomy
      implications for uterine artery embolization.

PMID- 21070911
TI  - [Folic acid intake from diet and supplements in a population of pregnant women in
      Valencia, Spain].
AB  - BACKGROUND AND OBJECTIVES: We examined the dietary intake and the use of
      supplements of folic acid (FA) in a cohort of pregnant women. We also explored
      the factors associated with non-compliance of both the recommended intake (RI) of
      600 MUg/day and the supplement use of 400 MUg/day provided to prevent neural tube
      defects (NTD). PATIENTS AND METHODS: We studied 782 pregnant women from the INMA
      Valencia cohort. The dietary intake was estimated using a food frequency
      questionnaire in two periods of pregnancy; from preconception to the second month
      and from the 3rd to the 7th month. Information on supplement use was also
      collected which allowed us to estimate the total FA intake (diet+supplements). We
      explored factors associated with non-compliance of the recommendations by
      logistic regression. RESULTS: The periconceptional mean daily FA intake was 304
      MUg/day. FA supplements were taken by 19.2, 30.2 and 66.2% of women in
      preconception, first and second month of pregnancy, respectively. Among women
      using supplements in periconception, 30% exceeded the tolerable upper intake
      level (UL) of 1.000 MUg/day. Non-compliance with RI was more common among women
      of foreign origin, of low educational level, who smoked, with unplanned
      pregnancy, who did not visit a private gynaecologist, who had had children or
      without previous medical illness. CONCLUSIONS: Diet by itself is not sufficient
      to reach RI for FA during pregnancy and many women initiate supplement use after
      the recommended period and inadequately. The youngest women, with lowest
      educational attainment and unplanned pregnancies are more likely not to comply.

PMID- 21070912
TI  - [Holt-Oram syndrome: study of 7 cases].
AB  - FUNDAMENTAL AND OBJECTIVE: Holt-Oram syndrome (HOS) is a heart-hand disease with
      an autosomal dominant inheritance pattern. About 85% of the affected patients
      present de novo mutations in the TBX5 gene. The aim of this study is to propose a
      molecular strategy to diagnose patients with clinical suspicion of HOS. PATIENTS
      AND METHODS: A sequence analysis of 7 patients from exon 2 to exon 8 of the TBX5
      gene was performed. MLPAp179 and MLPAp180 were performed in those cases in which
      no mutation was found. RESULTS: p.Arg270X and p.Ala34Glyfsx27 mutations were
      identified in 2 cases. These cases fulfilled the strict clinical criteria, had a
      family history of HOS and had similar clinical features. In other three cases,
      MLPA results showed deletions of the GLI3 coding region. CONCLUSIONS: In order to
      increase the TBX5 mutation detection rate, an exhaustive physical examination
      focused on the strict clinical criteria may be necessary to rule out clinical
      overlapping syndromes. We propose that molecular analysis of GLI3 may be
      performed in patients with clinical suspicion of HOS without mutations in TBX5.

PMID- 21070913
TI  - Mechanisms of prostate cancer initiation and progression.
AB  - Prostate cancer is a major health problem as it continues to be the most
      frequently diagnosed cancer in men in the Western world. While improved early
      detection significantly decreased mortality, prostate cancer still remains the
      second leading cause of cancer-related death in Western men. Understanding the
      mechanisms of prostate cancer initiation and progression should have a
      significant impact on development of novel therapeutic approaches that can help
      to combat this disease. The recent explosion of novel high-throughput genetic
      technologies together with studies in animal models and human tissues allowed a
      comprehensive analysis and functional validation of the molecular changes. This
      chapter will summarize and discuss recently identified critical genetic and
      epigenetic changes that drive prostate cancer initiation and progression. These
      discoveries should help concentrate the efforts of drug development on key
      pathways and molecules, and finally translate the knowledge that is gained from
      mechanistic studies into effective treatments.

PMID- 21070914
TI  - Genetic basis for susceptibility to lung cancer: Recent progress and future
      directions.
AB  - Lung cancer is the leading cause of cancer death worldwide, and cigarette smoking
      is the major environmental factor for its development. To elucidate the genetic
      differences in the susceptibility to lung cancer among individuals, genetic
      factors involved in tobacco-induced lung cancers have been extensively
      investigated and a number of genetic polymorphisms have been identified to date
      as candidates. Most of the polymorphisms identified are of genes encoding
      proteins associated with the activity to metabolize tobacco smoke carcinogens and
      to suppress mutations induced by those carcinogens, and functional significances
      have been elucidated for some of these polymorphisms. However, the significance
      of these polymorphisms in the contribution to lung cancer development still
      remains unclear. Recently, several novel lung cancer susceptibility genes,
      including those on chromosomes 5p15.33, 6p21, and 15q24-25.1, have been
      identified by large-scale genome-wide association (GWA) studies. The 15q25 region
      contains three nicotine acetylcholine receptor subunit genes, and their
      polymorphisms have been also reported as being associated with nicotine
      dependence. The 5p15.33 region is associated with risks specifically for lung
      adenocarcinoma, the commonest histological type and weakly associated with
      smoking. This locus has been shown to be associated with risks for a wide variety
      of cancers, including lung adenocarcinoma. Associations of the 6q21 region have
      not been consistently replicated among studies. The 6q23-25 and 13q31.3 regions
      were also identified by recent GWA studies as being associated with risk for lung
      cancer, particularly in never-smokers. However, contributions of genetic
      differences on these five loci to the susceptibility to overall lung cancer seem
      to be small. There are several molecular pathways for the development of lung
      adenocarcinomas, and environmental factors for their development are still
      unclear, especially those in never-smokers. In addition, geographic differences
      as well as gender differences in lung cancer risk have been indicated.
      Furthermore, various genes identified by candidate gene association studies have
      not been reevaluated for their significance together with genes identified by GWA
      studies in the same population. Therefore, further studies will be necessary to
      assess the individual susceptibility to lung cancer based on the combination of
      polymorphisms in multiple genes, and to establish a novel way of evaluating the
      individual risk for lung cancer for its prevention.

PMID- 21070915
TI  - Functional and clinical relevance of chondroitin sulfate proteoglycan 4.
AB  - The lack of effective conventional therapies for the treatment of advanced stage
      melanoma has stimulated interest in the development of novel strategies for the
      management of patients with malignant melanoma. Among them, immunotherapy has
      attracted much attention because of the potential role played by immunological
      events in the clinical course of melanoma. For many years, T cell-based
      immunotherapy has been emphasized in part because of the disappointing results of
      the monoclonal antibody (mAb)-based clinical trials conducted in the early 1980s
      and in part because of the postulated major role played by T cells in tumor
      growth control. More recently, mAb-based therapies have gained in popularity
      given their clinical and commercial success for a variety of malignant diseases.
      As a result, there has been increased interest in identifying and characterizing
      antibody-defined melanoma antigens. Among them, the chondroitin sulfate
      proteoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated
      antigen (HMW-MAA) or melanoma chondroitin sulfate proteoglycan (MCSP), has
      attracted much attention in recent years because of the growing experimental
      evidence that it fulfills two requirements for immunotherapy to be
      therapeutically effective: (1) targeting of cancer stem cells (CSC) and (2)
      development of combinatorial therapies to counteract the escape mechanisms driven
      by the genetic instability of tumor cells. With this in mind, in this chapter, we
      have reviewed recent information related to the distribution of CSPG4 on various
      types of tumors, including CSC, its expression on pericytes in the tumor
      microenvironment, its recognition by T cells, its role in cell biology as well as
      the potential mechanisms underlying the ability of CSPG4-specific immunity to
      control malignant cell growth.

PMID- 21070916
TI  - KRAS signaling pathway alterations in microsatellite unstable gastrointestinal
      cancers.
AB  - Microsatellite instability (MSI) occurs in about 15% of gastrointestinal cancers
      and it is associated with specific clinic, pathologic, and molecular features of
      the tumors. MSI-high (MSI-H) carcinomas also follow specific tumor development
      pathways. This review is focused on the molecular profile of alterations in
      members of the KRAS signaling pathway (EGFR, KRAS, BRAF, PIK3CA, RASSF1A, and
      MLK3 genes) in MSI gastrointestinal carcinomas. Alterations in these genes
      characterize more than half of gastrointestinal cancers and frequently occur
      simultaneously in the same tumor, pinpointing the KRAS signaling pathway as one
      of the most frequently altered pathways in this subset of cancers. Nowadays, many
      and novel inhibitors targeting molecules of this signaling pathway are being
      described; therefore, it is worthwhile to test their efficacy in MSI
      gastrointestinal cancers in order to develop new and more directed targeted
      therapies for patients affected by this disease.

PMID- 21070917
TI  - Azygous continuation of inferior vena cava.

PMID- 21070918
TI  - Antithrombotic therapy in the elderly.
AB  - Antithrombotic therapy represents the mainstay of treatment for prevention of
      recurrent ischemic events in patients with atherothrombotic disease processes.
      Although the benefits of antithrombotic pharmacotherapy in the elderly are well
      established, the elderly are generally more vulnerable to the adverse effects of
      antithrombotic drugs. Such higher vulnerability may be related to distinct
      pharmacokinetic and pharmacodynamic responses in the late age of life, during
      which drug-drug interactions due to polypharmacy further enhance the risk of
      adverse effects associated with the use of antithrombotic agents. Given that the
      prevalence of atherothrombotic disease, as well as diseases with thromboembolic
      potential, increases exponentially with age and that the elderly population is in
      continuous growth, understanding strategies of antithrombotic management in these
      patients is of key importance. The present paper provides an overview of the
      current available evidence on the use of antithrombotic therapy in elderly
      patients with the primary focus on treatment of coronary artery disease.

PMID- 21070919
TI  - Immunologic and inflammatory reactions to exogenous stem cells implications for
      experimental studies and clinical trials for myocardial repair.
AB  - Intense research is under way to determine the optimal stem cell type and regimen
      for repairing diseased myocardium. Although initial studies in humans focused on
      the use of homologous stem cells, allogeneic or xenogeneic stem cells have been
      studied extensively in experimental work. Clinical trials with allogeneic stem
      cells are now under way, an approach based on the premise that stem cells and
      precursor cells are characterized as being immunotolerant. However, evidence
      indicates that stem cells may gain immune potency in vivo, especially when
      delivered to inflamed tissue, such as acutely infarcted myocardium.
      Histopathologic studies show the presence of a lymphohistiocytic inflammatory
      reaction at the sites of delivery of allogeneic stem cells, a response that is
      exaggerated with the use of xenogeneic stem cells. The immune-mediated
      inflammatory reaction to allogeneic and xenogeneic stem cells may elicit a
      spectrum of effects, ranging from beneficial (e.g., increased paracrine activity)
      to detrimental (e.g., accelerated damage and removal of stem cells). Although the
      issue of immune-mediated inflammatory responses to non-self stem cells requires
      further evaluation, non-self stem cells should not be considered as
      immunologically inert or exclusively immunosuppressive in vivo.

PMID- 21070920
TI  - Effects of telmisartan added to Angiotensin-converting enzyme inhibitors on
      mortality and morbidity in hemodialysis patients with chronic heart failure a
      double-blind, placebo-controlled trial.
AB  - OBJECTIVES: the aim of this study was to determine whether telmisartan decreases
      all-cause and cardiovascular mortality and morbidity in hemodialysis patients
      with chronic heart failure (CHF) and impaired left ventricular ejection fraction
      (LVEF) when added to standard therapies with angiotensin-converting enzyme
      inhibitors. BACKGROUND: in hemodialysis patients, CHF is responsible for a high
      mortality rate, but presently very few data are available with regard to this
      population. METHODS: A 3-year randomized, double-blind, placebo-controlled,
      multicenter trial was performed involving 30 Italian clinics. Hemodialysis
      patients with CHF (New York Heart Association functional class II to III; LVEF <=
      40%) were randomized to telmisartan or placebo in addition to angiotensin
      converting enzyme inhibitor therapy. A total of 332 patients were enrolled (165
      telmisartan, 167 placebo). Drug dosage was titrated to a target dose of
      telmisartan of 80 mg or placebo. Mean follow-up period was 35.5 +/- 8.5 months
      (median: 36 months; range: 2 to 40 months). Primary outcomes were: 1) all-cause
      mortality; 2) cardiovascular mortality; and 3) CHF hospital stay. RESULTS: at 3
      years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p
      < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital
      admission for CHF (33.9% vs. 55.1%; p < 0.0001). With Cox proportional hazards
      analysis, telmisartan was an independent determinant of all-cause mortality
      (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01),
      cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and
      hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51;
      p < 0.0001). Adverse effects, mainly hypotension, occurred in 16.3% of the
      telmisartan group versus 10.7% in the placebo group. CONCLUSIONS: addition of
      telmisartan to standard therapies significantly reduces all-cause mortality,
      cardiovascular death, and heart failure hospital stays in hemodialysis patients
      with CHF and LVEF <= 40%. (Effects Of Telmisartan Added To Angiotensin Converting
      Enzyme Inhibitors On Mortality And Morbidity In Haemodialysed Patients With
      Chronic Heart Failure: A Double-Blind Placebo-Controlled Trial; NCT00490958).

PMID- 21070921
TI  - Treating heart failure on dialysis. Finally getting some evidence.

PMID- 21070922
TI  - Assessment of conventional cardiovascular risk factors and multiple biomarkers
      for the prediction of incident heart failure and atrial fibrillation.
AB  - OBJECTIVES: the purpose of this study was to assess the predictive accuracy of
      conventional cardiovascular risk factors for incident heart failure and atrial
      fibrillation, and the added benefit of multiple biomarkers reflecting diverse
      pathophysiological pathways. BACKGROUND: heart failure and atrial fibrillation
      are interrelated cardiac diseases associated with substantial morbidity and
      mortality and increasing incidence. Data on prediction and prevention of these
      diseases in healthy individuals are limited. METHODS: in 5,187 individuals from
      the community-based MDCS (Malmo Diet and Cancer Study), we studied the
      performance of conventional risk factors and 6 biomarkers including midregional
      pro-atrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic
      peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive
      protein (CRP), and copeptin. RESULTS: during a mean follow-up of 14 years, 112
      individuals were diagnosed with heart failure and 284 individuals with atrial
      fibrillation. NT-proBNP (hazard ratio [HR]: 1.63 per SD, 95% confidence interval
      [CI]: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p <
      0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted
      incident heart failure independently of conventional risk factors and other
      biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR:
      1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial
      fibrillation. Addition of biomarkers to conventional risk factors improved c
      statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for
      atrial fibrillation and the integrated discrimination improvement for both
      diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was
      observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for
      atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of
      individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%).
      Addition of CRP to natriuretic peptides did not improve discrimination or
      reclassification. CONCLUSIONS: conventional cardiovascular risk factors predict
      incident heart failure and atrial fibrillation with reasonable accuracy in middle
      age individuals free from disease. Natriuretic peptides, but not other
      biomarkers, improve discrimination modestly for both diseases above and beyond
      conventional risk factors and substantially improve risk classification for heart
      failure.

PMID- 21070925
TI  - Left atrial roof ablation is more important than pulmonary vein isolation in
      terminating persistent atrial fibrillation in a canine model should we perform a
      left atrial roof line in all atrial fibrillation ablations?

PMID- 21070924
TI  - Roles of the left atrial roof and pulmonary veins in the anatomic substrate for
      persistent atrial fibrillation and ablation in a canine model.
AB  - OBJECTIVES: the aim of this study was to establish the electrophysiological
      consequences of pulmonary vein encircling ablation (PVEA) and linear left atrial
      roof ablation (LARA) for the atrial fibrillation (AF) substrate in an
      experimental model. BACKGROUND: sequential application of ablation lesions is
      often used in the management of AF, almost always incorporating PVEA and LARA.
      METHODS: Atrial tachypacing (400 beats/min, 5 weeks) was used to create an AF
      substrate in 13 dogs. PVEA and LARA were applied in randomized order. Regional
      atrial refractoriness, AF vulnerability, AF duration, and activation during AF
      were assessed before and after applying ablation lesion sets. RESULTS: PVEA
      failed to terminate AF or affect AF duration (742 +/- 242 s before vs. 627 +/-
      227 s after PVEA) but decreased AF vulnerability to single extrastimuli from 91
      +/- 4% to 59 +/- 5% (p < 0.001) by increasing effective refractory periods at
      sites with suppressed AF induction (from 78 +/- 4 ms to 102 +/- 8 ms, p < 0.01).
      LARA terminated AF in 67% of dogs (p < 0.05 vs. PVEA) and reduced AF duration
      (from 934 +/- 232 s to 322 +/- 183 s, p < 0.01) without affecting AF
      vulnerability. Baseline AF mapping showed left atrial (LA)-dominant complex
      reactivations (LA 9.4 +/- 0.9 vs. right atrial 1.1 +/- 0.3 reactivations/500-ms
      window, p < 0.001), with the LA roof frequently involved in re-entry circuits (44
      +/- 9% of LA reactivations). LARA terminated AF by interrupting LA roof
      reactivation circuits. In 5 of 13 cases, macro-re-entrant tachycardias (usually
      perimitral) occurred after LARA eliminated persistent AF. CONCLUSIONS: both PVEA
      and LARA had beneficial but limited actions in this canine model. LARA suppressed
      AF perpetuation by interrupting LA roof reactivation, without affecting AF
      vulnerability. PVEA suppressed AF initiation by prolonging regional effective
      refractory period but failed to affect the AF-perpetuating substrate. These
      findings indicate the need to systematically study individual stepwise components
      to refine AF ablation procedures.

PMID- 21070923
TI  - Depression as a potential modulator of Beta-adrenergic-associated leukocyte
      mobilization in heart failure patients.
AB  - OBJECTIVES: the aim of this study was to determine whether depressive symptoms
      are related to alterations in the sensitivity of peripheral blood mononuclear
      cells to beta-adrenergic agonists in patients with heart failure (HF) by
      measuring in vitro chemotaxis (CTX) to isoproterenol at rest and after acute
      exercise in patients with HF and controls. BACKGROUND: clinical outcomes are
      worse for patients with HF presenting with symptoms of depression.
      Sympathetically modulated immune dysregulation associated with depression may be
      one mechanism leading to worse prognosis. METHODS: seventy-seven patients with HF
      and 44 controls (mean age 56.4 +/- 1.3 years) completed the Beck Depression
      Inventory and a 15-min mild-graded exercise task on a stationary bicycle.
      Exercise intensity was kept relative to fitness levels for all participants by
      gradually increasing resistance to reach a Borg scale subjective rating of 12 to
      13, "somewhat hard." Plasma norepinephrine and epinephrine levels were measured
      before and after exercise. Chemotaxis to isoproterenol was determined by
      measuring in vitro peripheral blood mononuclear cell migration through a modified
      Boyden chamber. RESULTS: In patients with HF, depressive symptom severity was
      associated with greater CTX after exercise (p = 0.001). Higher resting
      norepinephrine in patients with HF was also associated with increased CTX to
      exercise (p = 0.03). CONCLUSIONS: patients with HF with higher depressive
      symptoms and norepinephrine exhibited increased peripheral blood mononuclear cell
      CTX to isoproterenol to mild exercise, suggesting greater beta-adrenergic
      sensitivity. Increased immune migration in patients with HF who have elevated
      depressive symptoms could be associated with cardiac remodeling and HF disease
      progression.

PMID- 21070926
TI  - Aortic valve reinterventions after balloon aortic valvuloplasty for congenital
      aortic stenosis intermediate and late follow-up.
AB  - OBJECTIVES: the aim of this study was to evaluate the long-term results of
      transcatheter balloon aortic valvuloplasty, the preferred treatment for
      congenital aortic stenosis (AS). BACKGROUND: aortic valve function and
      reintervention late after this procedure are not well characterized. METHODS:
      from 1985 to 2008, 563 patients underwent balloon dilation for congenital AS.
      After excluding those converted to univentricular circulation and/or died <= 30
      days after the procedure, 509 patients constituted the study cohort. RESULTS: The
      median follow-up period was 9.3 years (range 0.1 to 23.6 years); cumulative
      follow-up was 5,003 patient-years. The median age was 2.4 years (range 1 day to
      40.5 years), and most patients (73%) had isolated native AS. Peak AS gradients
      decreased significantly after dilation (median decrease, 35 mm Hg), and acute
      post-dilation aortic regurgitation was moderate or greater in 70 patients (14%).
      Older patients more often had post-dilation aortic regurgitation (p < 0.001).
      During follow-up, 225 patients (44%) underwent aortic valve reintervention:
      repeat balloon dilation in 115 (23%), aortic valve repair in 65 (13%), and aortic
      valve replacement in 116 (23%). Survival free from any aortic valve
      reintervention was 89 +/- 1% at 1 year, 72 +/- 2% at 5 years, 54 +/- 3% at 10
      years, and 27 +/- 3% at 20 years. Freedom from aortic valve replacement was 90 +/
      2% at 5 years, 79 +/- 3% at 10 years, and 53 +/- 4% at 20 years. In multivariate
      analyses, lower post-dilation AS gradient and lower grade of post-dilation aortic
      regurgitation were associated with longer freedom from aortic valve replacement,
      but age, era, and pre-dilation AS severity were not. CONCLUSIONS: although
      transcatheter aortic valvuloplasty is effective for relief of congenital AS,
      there are steady long-term hazards for surgical aortic valve reintervention and
      replacement that are independent of age at initial intervention or AS severity.

PMID- 21070927
TI  - Shifting the balance between aortic insufficiency and residual gradients after
      balloon aortic valvuloplasty.

PMID- 21070929
TI  - Singleton-merten syndrome and impaired cardiac function.

PMID- 21070930
TI  - Between a rock and a hard place.

PMID- 21070928
TI  - Bisphosphonate Use and Prevalence of Valvular and Vascular Calcification in Women
      MESA (The Multi-Ethnic Study of Atherosclerosis).
AB  - OBJECTIVES: the aim of this study was to determine whether nitrogen-containing
      bisphosphonate (NCBP) therapy is associated with the prevalence of cardiovascular
      calcification. BACKGROUND: cardiovascular calcification correlates with
      atherosclerotic disease burden. Experimental data suggest that NCBP might limit
      cardiovascular calcification, which has implications for disease prevention.
      METHODS: the relationship of NCBP use to the prevalence of aortic valve, aortic
      valve ring, mitral annulus, thoracic aorta, and coronary artery calcification
      (AVC, AVRC, MAC, TAC, and CAC, respectively) detected by computed tomography was
      assessed in 3,710 women within the MESA (Multi-Ethnic Study of Atherosclerosis)
      with regression modeling. RESULTS: Analyses were age-stratified, because of a
      significant interaction between age and NCBP use (interaction p values: AVC p <
      0.0001; AVRC p < 0.0001; MAC p = 0.002; TAC p < 0.0001; CAC p = 0.046). After
      adjusting for age; body mass index; demographic data; diabetes; smoking; blood
      pressure; cholesterol levels; and statin, hormone replacement, and renin
      angiotensin inhibitor therapy, NCBP use was associated with a lower prevalence of
      cardiovascular calcification in women >= 65 years of age (prevalence ratio: AVC
      0.68 [95% confidence interval (CI): 0.41 to 1.13]; AVRC 0.65 [95% CI: 0.51 to
      0.84]; MAC 0.54 [95% CI: 0.33 to 0.93]; TAC 0.69 [95% CI: 0.54 to 0.88]; CAC 0.89
      [95% CI: 0.78 to 1.02]), whereas calcification was more prevalent in NCBP users
      among the 2,181 women <65 years of age (AVC 4.00 [95% CI: 2.33 to 6.89]; AVRC
      1.92 [95% CI: 1.42 to 2.61]; MAC 2.35 [95% CI: 1.12 to 4.84]; TAC 2.17 [95% CI:
      1.49 to 3.15]; CAC 1.23 [95% CI: 0.97 to 1.57]). CONCLUSIONS: among women in the
      diverse MESA cohort, NCBPs were associated with decreased prevalence of
      cardiovascular calcification in older subjects but more prevalent cardiovascular
      calcification in younger ones. Further study is warranted to clarify these age
      dependent NCBP effects.

PMID- 21070932
TI  - The Weasel Clause: Excluding Patients From Door-to-Balloon Analyses.

PMID- 21070933
TI  - Serial intravascular ultrasound examinations and clinical outcome.

PMID- 21070935
TI  - ACCF/AHA new insights into the methodology of performance measurement: a report
      of the American College of Cardiology Foundation/American Heart Association Task
      Force on performance measures.

PMID- 21070936
TI  - An ATPase R-finger leaves its print on transcriptional activation.
AB  - Bacterial enhancer-binding proteins (bEBPs) are AAA+ ATPases that remodel sigma54
      RNA polymerase holoenzyme for transcription. Chen et al., in this issue of
      Structure, show the R-finger, a conserved AAA+ arginine residue, drives
      structural changes that allow the ATP-bound bEBP to engage sigma54 en route to
      remodeling.

PMID- 21070937
TI  - Myosin VI: how do charged tails exert control?
AB  - Molecular dynamics simulations and single molecule experiments are used to
      suggest that charged helices in the medial tail domain participate in myosin VI
      dimerization (Kim et al., 2010), which reinforces the mechanism that unfolding of
      the three helix bundle in the proximal tail serves as a lever arm extension.

PMID- 21070938
TI  - A glimpse at regulation of nitrogen homeostasis.
AB  - NrpR is a 2-oxoglutarate (2OG)-sensing transcription factor found in the archaeal
      phylum euryarchaetoa. When 2OG concentrations are low, NrpR transcriptionally
      represses expression of the nitrogen acquisition genes. Structural studies by
      Wisedchaisri et al. (2010) have identified the cleft region, where 2OG binds to
      NrpR. Their study has highlighted conservation of 2OG-binding residues among
      other 2OG-responsive proteins.

PMID- 21070939
TI  - MoDEL (Molecular Dynamics Extended Library): a database of atomistic molecular
      dynamics trajectories.
AB  - More than 1700 trajectories of proteins representative of monomeric soluble
      structures in the protein data bank (PDB) have been obtained by means of state-of
      the-art atomistic molecular dynamics simulations in near-physiological
      conditions. The trajectories and analyses are stored in a large data warehouse,
      which can be queried for dynamic information on proteins, including interactions.
      Here, we describe the project and the structure and contents of our database, and
      provide examples of how it can be used to describe the global flexibility
      properties of proteins. Basic analyses and trajectories stripped of solvent
      molecules at a reduced resolution level are available from our web server.

PMID- 21070940
TI  - Raman-assisted crystallography suggests a mechanism of X-ray-induced disulfide
      radical formation and reparation.
AB  - X-ray-induced chemistry modifies biological macromolecules structurally and
      functionally, even at cryotemperatures. The mechanisms of x-radiation damage in
      colored or redox proteins have often been investigated by combining X-ray
      crystallography with in crystallo-ultraviolet-visible spectroscopy. Here, we used
      Raman microspectrophotometry to follow the onset of damage in crystalline
      lysozyme, notably that of disulfide bond breakage. The dose-dependent Raman
      spectra are consistent with a kinetic model for the rupture of disulfide bonds
      suggesting the rapid build up of an anionic radical intermediate. This
      intermediate may either revert back to the oxidized state or evolve toward
      protonated radical species or cleaved products. The data strongly suggest that
      back conversion of the anionic radical is significantly accelerated by X-rays,
      revealing an X-ray-induced "repair" mechanism. The possibility of X-ray-induced
      chemical repair is an important feature to take into account when assessing
      radiation damage in macromolecules.

PMID- 21070941
TI  - Engagement of arginine finger to ATP triggers large conformational changes in
      NtrC1 AAA+ ATPase for remodeling bacterial RNA polymerase.
AB  - The NtrC-like AAA+ ATPases control virulence and other important bacterial
      activities through delivering mechanical work to sigma54-RNA polymerase to
      activate transcription from sigma54-dependent genes. We report the first crystal
      structure for such an ATPase, NtrC1 of Aquifex aeolicus, in which the catalytic
      arginine engages the gamma-phosphate of ATP. Comparing the new structure with
      those previously known for apo and ADP-bound states supports a rigid-body
      displacement model that is consistent with large-scale conformational changes
      observed by low-resolution methods. First, the arginine finger induces rigid-body
      roll, extending surface loops above the plane of the ATPase ring to bind sigma54.
      Second, ATP hydrolysis permits Pi release and retraction of the arginine with a
      reversed roll, remodeling sigma54-RNAP. This model provides a fresh perspective
      on how ATPase subunits interact within the ring-ensemble to promote
      transcription, directing attention to structural changes on the arginine-finger
      side of an ATP-bound interface.

PMID- 21070942
TI  - XLF regulates filament architecture of the XRCC4.ligase IV complex.
AB  - DNA ligase IV (LigIV) is critical for nonhomologous end joining (NHEJ), the major
      DNA double-strand break (DSB) repair pathway in human cells, and LigIV activity
      is regulated by XRCC4 and XLF (XRCC4-like factor) interactions. Here, we employ
      small angle X-ray scattering (SAXS) data to characterize three-dimensional
      arrangements in solution for full-length XRCC4, XRCC4 in complex with LigIV
      tandem BRCT domains and XLF, plus the XRCC4.XLF.BRCT2 complex. XRCC4 forms
      tetramers mediated through a head-to-head interface, and the XRCC4 C-terminal
      coiled-coil region folds back on itself to support this interaction. The
      interaction between XLF and XRCC4 is also mediated via head-to-head interactions.
      In the XLF.XRCC4.BRCT complex, alternating repeating units of XLF and XRCC4.BRCT
      place the BRCT domain on one side of the filament. Collective results identify
      XRCC4 and XLF filaments suitable to align DNA molecules and function to
      facilitate LigIV end joining required for DSB repair in vivo.

PMID- 21070943
TI  - Formation of salt bridges mediates internal dimerization of myosin VI medial tail
      domain.
AB  - The unconventional motor protein, myosin VI, is known to dimerize upon cargo
      binding to its C-terminal end. It has been shown that one of its tail domains,
      called the medial tail domain, is a dimerization region. The domain contains an
      unusual pattern of alternating charged residues and a few hydrophobic residues.
      To reveal the unknown dimerization mechanism of the medial tail domain, we
      employed molecular dynamics and single-molecule experimental techniques. Both
      techniques suggest that the formation of electrostatic-based interhelical salt
      bridges between oppositely charged residues is a key dimerization factor. For the
      dimerization to occur, the two identical helices within the dimer do not bind in
      a symmetric fashion, but rather with an offset of about one helical repeat.
      Calculations of the dimer-dissociation energy find the contribution of
      hydrophobic residues to the dimerization process to be minor; they also find that
      the asymmetric homodimer state is energetically favorable over a state of
      separate helices.

PMID- 21070944
TI  - Structure of a SLC26 anion transporter STAS domain in complex with acyl carrier
      protein: implications for E. coli YchM in fatty acid metabolism.
AB  - Escherichia coli YchM is a member of the SLC26 (SulP) family of anion
      transporters with an N-terminal membrane domain and a C-terminal cytoplasmic STAS
      domain. Mutations in human members of the SLC26 family, including their STAS
      domain, are linked to a number of inherited diseases. Herein, we describe the
      high-resolution crystal structure of the STAS domain from E. coli YchM isolated
      in complex with acyl-carrier protein (ACP), an essential component of the fatty
      acid biosynthesis (FAB) pathway. A genome-wide genetic interaction screen showed
      that a ychM null mutation is synthetically lethal with mutant alleles of genes
      (fabBDHGAI) involved in FAB. Endogenous YchM also copurified with proteins
      involved in fatty acid metabolism. Furthermore, a deletion strain lacking ychM
      showed altered cellular bicarbonate incorporation in the presence of NaCl and
      impaired growth at alkaline pH. Thus, identification of the STAS-ACP complex
      suggests that YchM sequesters ACP to the bacterial membrane linking bicarbonate
      transport with fatty acid metabolism.

PMID- 21070945
TI  - Structural basis for error-free replication of oxidatively damaged DNA by yeast
      DNA polymerase eta.
AB  - 7,8-dihydro-8-oxoguanine (8-oxoG) adducts are formed frequently by the attack of
      oxygen-free radicals on DNA. They are among the most mutagenic lesions in cells
      because of their dual coding potential, where, in addition to normal base-pairing
      of 8-oxoG(anti) with dCTP, 8-oxoG in the syn conformation can base pair with
      dATP, causing G to T transversions. We provide here for the first time a
      structural basis for the error-free replication of 8-oxoG lesions by yeast DNA
      polymerase eta (Poleta). We show that the open active site cleft of Poleta can
      accommodate an 8-oxoG lesion in the anti conformation with only minimal changes
      to the polymerase and the bound DNA: at both the insertion and post-insertion
      steps of lesion bypass. Importantly, the active site geometry remains the same as
      in the undamaged complex and provides a basis for the ability of Poleta to
      prevent the mutagenic replication of 8-oxoG lesions in cells.

PMID- 21070946
TI  - Structure of yeast regulatory subunit: a glimpse into the evolution of PKA
      signaling.
AB  - The major cAMP receptors in eukaryotes are the regulatory (R) subunits of PKA, an
      allosteric enzyme conserved in fungi through mammals. While mammals have four R
      subunit genes, Saccharomyces cerevisiae has only one, Bcy1. To achieve a
      molecular understanding of PKA activation in yeast and to explore the evolution
      of cyclic-nucleotide binding (CNB) domains, we solved the structure of cAMP-bound
      Bcy1(168-416). Surprisingly, the relative orientation of the two CNB domains in
      Bcy1 is very different from mammalian R-subunits. This quaternary structure is
      defined primarily by a fungi-specific sequence in the hinge between the
      alphaB/alphaC helices of the CNB-A domain. The unique interface between the two
      CNB domains in Bcy1 defines the allosteric mechanism for cooperative activation
      of PKA by cAMP. Some interface motifs are isoform-specific while others, although
      conserved, play surprisingly different roles in each R-subunit. Phylogenetic
      analysis shows that structural differences in Bcy1 are shared by fungi of the
      subphylum Saccharomycotina.

PMID- 21070947
TI  - Hydrogen/deuterium exchange analysis of HIV-1 capsid assembly and maturation.
AB  - Following budding, HIV-1 virions undergo a maturation process where the Gag
      polyprotein in the immature virus is cleaved by the viral protease and rearranges
      to form the mature infectious virion. Despite the wealth of structures of
      isolated capsid domains and an in vitro-assembled mature lattice, models of the
      immature lattice do not provide an unambiguous model of capsid-molecule
      orientation and no structural information is available for the capsid maturation
      pathway. Here we have applied hydrogen/deuterium exchange mass spectrometry to
      immature, mature, and mutant Gag particles (CA5) blocked at the final Gag
      cleavage event to examine the molecular basis of capsid assembly and maturation.
      Capsid packing arrangements were very similar for all virions, whereas immature
      and CA5 virions contained an additional intermolecular interaction at the
      hexameric, 3-fold axis. Additionally, the N-terminal beta-hairpin was observed to
      form as a result of capsid-SP1 cleavage rather than driving maturation as
      previously postulated.

PMID- 21070948
TI  - Structure and flexibility of the complete periplasmic domain of BamA: the protein
      insertion machine of the outer membrane.
AB  - Folding and insertion of beta-barrel outer membrane proteins (OMPs) is essential
      for Gram-negative bacteria. This process is mediated by the multiprotein complex
      BAM, composed of the essential beta-barrel OMP BamA and four lipoproteins
      (BamBCDE). The periplasmic domain of BamA is key for its function and contains
      five "polypeptide transport-associated" (POTRA) repeats. Here, we report the
      crystal structure of the POTRA4-5 tandem, containing the essential for BAM
      complex formation and cell viability POTRA5. The domain orientation observed in
      the crystal is validated by solution NMR and SAXS. Using previously determined
      structures of BamA POTRA1-4, we present a spliced model of the entire BamA
      periplasmic domain validated by SAXS. Solution scattering shows that
      conformational flexibility between POTRA2 and 3 gives rise to compact and
      extended conformations. The length of BamA in its extended conformation suggests
      that the protein may bridge the inner and outer membranes across the periplasmic
      space.

PMID- 21070949
TI  - Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor
      P1 domain to the kinase.
AB  - Netrin receptor DCC plays critical roles in many cellular processes, including
      axonal outgrowth and migration, angiogenesis, and apoptosis, but the molecular
      basis of DCC-mediated signaling is largely unclear. ERK2, a member of the MAPK
      family, is one of the few proteins known to be involved in DCC-mediated
      signaling. Here, we report that ERK2 directly interacts with DCC, and the ERK2
      binding region was mapped to the conserved intracellular P1 domain of the
      receptor. The structure of ERK2 in complex with the P1 domain of DCC reveals that
      DCC contains a MAPK docking motif. The docking of the P1 domain onto ERK2
      physically positions several phosphorylation sites of DCC in the vicinity of the
      kinase active site. We further show that the docking interaction between the P1
      domain and ERK2 is essential for the ERK2-mediated phosphorylation of DCC. We
      conclude that DCC signaling is directly coupled with MAPK signaling cascades.

PMID- 21070950
TI  - Structural underpinnings of nitrogen regulation by the prototypical nitrogen
      responsive transcriptional factor NrpR.
AB  - Plants and microorganisms reduce environmental inorganic nitrogen to ammonium,
      which then enters various metabolic pathways solely via conversion of 2
      oxoglutarate (2OG) to glutamate and glutamine. Cellular 2OG concentrations
      increase during nitrogen starvation. We recently identified a family of 2OG
      sensing proteins--the nitrogen regulatory protein NrpR--that bind DNA and repress
      transcription of nitrogen assimilation genes. We used X-ray crystallography to
      determine the structure of NrpR regulatory domain. We identified the NrpR 2OG
      binding cleft and show that residues predicted to interact directly with 2OG are
      conserved among diverse classes of 2OG-binding proteins. We show that high levels
      of 2OG inhibit NrpRs ability to bind DNA. Electron microscopy analyses document
      that NrpR adopts different quaternary structures in its inhibited 2OG-bound state
      compared with its active apo state. Our results indicate that upon 2OG release,
      NrpR repositions its DNA-binding domains correctly for optimal interaction with
      DNA thereby enabling gene repression.

PMID- 21070951
TI  - Detailed analysis of function divergence in a large and diverse domain
      superfamily: toward a refined protocol of function classification.
AB  - Some superfamilies contain large numbers of protein domains with very different
      functions. The ability to refine the functional classification of domains within
      these superfamilies is necessary for better understanding the evolution of
      functions and to guide function prediction of new relatives. To achieve this, a
      suitable starting point is the detailed analysis of functional divisions and
      mechanisms of functional divergence in a single superfamily. Here, we present
      such a detailed analysis in the superfamily of HUP domains. A biologically
      meaningful functional classification of HUP domains is obtained manually.
      Mechanisms of function diversification are investigated in detail using this
      classification. We observe that structural motifs play an important role in
      shaping broad functional divergence, whereas residue-level changes shape
      diversity at a more specific level. In parallel we examine the ability of an
      automated protocol to capture the biologically meaningful classification, with a
      view to automatically extending this classification in the future.

PMID- 21070953
TI  - Osteolysis of the inferior surface of the acromion caused by knots of the suture
      thread after rotator cuff repair surgery: knot impingement after rotator cuff
      repair.

PMID- 21070952
TI  - Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP
      interaction.
AB  - Budding of HIV-1 requires the binding of the PTAP late domain of the Gag p6
      protein to the UEV domain of the TSG101 subunit of ESCRT-I. The normal function
      of this motif in cells is in receptor downregulation. Here, we report the 1.4-1.6
      A structures of the human TSG101 UEV domain alone and with wild-type and mutant
      HIV-1 PTAP and Hrs PSAP nonapeptides. The hydroxyl of the Thr or Ser residue in
      the P(S/T)AP motif hydrogen bonds with the main chain of Asn69. Mutation of the
      Asn to Pro, blocking the main-chain amide, abrogates PTAP motif binding in vitro
      and blocks budding of HIV-1 from cells. N69P and other PTAP binding-deficient
      alleles of TSG101 did not rescue HIV-1 budding. However, the mutant alleles did
      rescue downregulation of endogenous EGF receptor. This demonstrates that the PSAP
      motif is not rate determining in EGF receptor downregulation under normal
      conditions.

PMID- 21070954
TI  - An unusual cause of scapular winging following trauma in an army personnel.

PMID- 21070955
TI  - Systematic review of patient-administered shoulder functional scores on
      instability.
AB  - BACKGROUND: Shoulder instability is common. Multiple questionnaires are used in
      clinical studies. The purpose of this study is to find and synthesize evidence on
      the usefulness of self-administered questionnaires specific to shoulder
      instability. MATERIALS AND METHODS: We undertook a systematic review using a
      standard search strategy (publications from 1966-2008) on databases (Medline,
      Embase); a structured search was conducted and supplemented by expert
      consultation. Raters conducted data extraction and critical appraisal using
      structured tools. A descriptive synthesis was performed. RESULTS: In total, 25
      published questionnaires used for patients with shoulder instability were
      identified. The Rowe questionnaire is the oldest and the most frequently used
      scale. After excluding questionnaires that were not validated, that necessitated
      physical examination, or that did not address instability symptoms, we identified
      3 validated self-report measures specific to shoulder instability: Western
      Ontario Shoulder Instability Index (WOSI), Oxford Shoulder Instability
      Questionnaire, and Melbourne Instability Shoulder Scale. Quality ratings on
      validation studies varied from 50% to 79%. A failure to establish clear
      guidelines for interpretation was a common flaw. Although there are insufficient
      studies (n = 3) to determine the best measure, the WOSI appears to have the best
      supporting evidence with excellent reliability/responsiveness (intraclass
      correlation coefficient, 0.95; effect size, 0.93). CONCLUSIONS: Evidence for the
      psychometric properties of shoulder instability is limited but suggests that
      reliable and responsive measures are available. More studies of the WOSI and
      competing scales in head-to-head comparison are needed to determine their optimal
      usage. Cultural adaptation is also needed to permit widespread usage. CLINICAL
      RELEVANCE: Reliable and responsive measures are available to evaluate patients
      with shoulder instability.

PMID- 21070956
TI  - Anatomical variations of the anterosuperior labrum: prevalence and association
      with type II superior labrum anterior-posterior (SLAP) lesions.
AB  - BACKGROUND: Anterosuperior labrum variations have been generally described as
      innocent anatomical variations without clinical significance. This study was
      intended to determine their prevalence and reveal their possible relationship
      with type II SLAP lesions. MATERIALS AND METHODS: A total of 713 consecutive
      shoulder arthroscopies were evaluated retrospectively for anterosuperior labrum
      variations and co-existing labral pathologies. Twenty two of these were excluded
      from the study due to the interobserver variability in the categorization
      process. The relationship of both these anatomic variants and shoulders with a
      normal appearing anterosuperior labrum to intra-articular pathology was analyzed
      statistically and compared with each other. RESULTS: Found in 98 patients
      (14.18%), the anatomic variations in the anterosuperior labrum were classified
      into 3 groups as the sublabral recess (2.46%), the sublabral foramen (7.67%), and
      absent anterosuperior labrum with a cord-like middle glenohumeral ligament
      (4.05%). The latter 2 of these groups displayed a statistically significant
      relationship with type II SLAP lesions (21 of 53 and 23 of 28 patients; P = .0028
      and P < .0001, respectively). DISCUSSION: Although mostly considered as simple
      morphological variations, the anatomic variants of the anterosuperior labrum may
      predispose the shoulder to labrum pathologies by altering the intra-articular
      biomechanics. CONCLUSION: As previously suggested in the literature, certain
      anatomic variants of the anterosuperior labrum are associated with the
      development of SLAP lesions.

PMID- 21070957
TI  - Opioid-mediated drug actions cannot be concluded from naloxone induced reversal
      of anti-nociceptive effects in behavioural tests only.

PMID- 21070958
TI  - Comments on "Recommendations on terminology and practice of psychophysical DNIC
      testing" by Yarnitsky et al., 14 (4), 339.

PMID- 21070959
TI  - SETting the clock for histone H4 monomethylation.
AB  - In this and a previous issue of Molecular Cell, Oda et al. (2010), Abbas et al.
      (2010), and Centore et al. (2010) determined that the H4K20 histone
      methyltransferase PR-Set7/Set8 is posttranslationally regulated by the PCNA
      dependent CRL4(Cdt2) ubiquitin ligase.

PMID- 21070960
TI  - Achieving fidelity in homologous recombination despite extreme complexity:
      informed decisions by molecular profiling.
AB  - In this issue of Molecular Cell, Savir and Tlusty (2010) apply signal detection
      theory to show that homologous recombination machinery is optimally tuned to find
      homologous DNA sequences within an exceptionally high background of heterologous
      sequences.

PMID- 21070961
TI  - Alternate endings: a new story for mRNA decapping.
AB  - With most of the important players identified, the process of decapping is
      thought, for the most part, to be well understood. In this issue of Molecular
      Cell, Song et al. (2010) challenge this notion with the identification of a
      previously uncharacterized mRNA decapping enzyme.

PMID- 21070962
TI  - A PSHaver for centromeric histones.
AB  - In this issue of Molecular Cell, Hewawasam et al. (2010) and Ranjitkar et al.
      (2010) identify and characterize Psh1, an E3 ubiquitin ligase that specifically
      targets the centromeric histone Cse4 in budding yeast and limits its
      misincorporation at noncentromeric regions.

PMID- 21070963
TI  - Mec1 is one of multiple kinases that prime the Mcm2-7 helicase for
      phosphorylation by Cdc7.
AB  - Activation of the eukaryotic replicative DNA helicase, the Mcm2-7 complex,
      requires phosphorylation by Cdc7/Dbf4 (Dbf4-dependent kinase or DDK), which, in
      turn, depends on prior phosphorylation of Mcm2-7 by an unknown kinase (or
      kinases). We identified DDK phosphorylation sites on Mcm4 and Mcm6 and found that
      phosphorylation of either subunit suffices for cell proliferation. Importantly,
      prior phosphorylation of either S/T-P or S/T-Q motifs on these subunits is
      required for DDK phosphorylation of Mcm2-7 and for normal S phase passage.
      Phosphomimetic mutations of DDK target sites bypass both DDK function and
      mutation of the priming phosphorylation sites. Mrc1 facilitates Mec1
      phosphorylation of the S/T-Q motifs of chromatin-bound Mcm2-7 during S phase to
      activate replication. Genetic interactions between priming site mutations and
      MRC1 or TOF1 deletion support a role for these modifications in replication fork
      stability. These findings identify regulatory mechanisms that modulate origin
      firing and replication fork assembly during cell cycle progression.

PMID- 21070964
TI  - A Shld1-controlled POT1a provides support for repression of ATR signaling at
      telomeres through RPA exclusion.
AB  - We previously proposed that POT1 prevents ATR signaling at telomeres by excluding
      RPA from the single-stranded TTAGGG repeats. Here, we use a Shld1-stabilized
      degron-POT1a fusion (DD-POT1a) to study the telomeric ATR kinase response. In the
      absence of Shld1, DD-POT1a degradation resulted in rapid and reversible
      activation of the ATR pathway in G1 and S/G2. ATR signaling was abrogated by
      shRNAs to ATR and TopBP1, but shRNAs to the ATM kinase or DNA-PKcs did not affect
      the telomere damage response. Importantly, ATR signaling in G1 and S/G2 was
      reduced by shRNAs to RPA. In S/G2, RPA was readily detectable at dysfunctional
      telomeres, and both POT1a and POT1b were required to exclude RPA and prevent ATR
      activation. In G1, the accumulation of RPA at dysfunctional telomeres was
      strikingly less, and POT1a was sufficient to repress ATR signaling. These results
      support an RPA exclusion model for the repression of ATR signaling at telomeres.

PMID- 21070965
TI  - RecA-mediated homology search as a nearly optimal signal detection system.
AB  - Homologous recombination facilitates the exchange of genetic material between
      homologous DNA molecules. This crucial process requires detecting a specific
      homologous DNA sequence within a huge variety of heterologous sequences. The
      detection is mediated by RecA in E. coli, or members of its superfamily in other
      organisms. Here, we examine how well the RecA-DNA interaction is adjusted to its
      task. By formulating the DNA recognition process as a signal detection problem,
      we find the optimal value of binding energy that maximizes the ability to detect
      homologous sequences. We show that the experimentally observed binding energy is
      nearly optimal. This implies that the RecA-induced deformation and the binding
      energetics are fine-tuned to ensure optimal sequence detection. Our analysis
      suggests a possible role for DNA extension by RecA, in which deformation enhances
      detection. The present signal detection approach provides a general recipe for
      testing the optimality of other molecular recognition systems.

PMID- 21070966
TI  - Analysis of active and inactive X chromosome architecture reveals the independent
      organization of 30 nm and large-scale chromatin structures.
AB  - Using a genetic model, we present a high-resolution chromatin fiber analysis of
      transcriptionally active (Xa) and inactive (Xi) X chromosomes packaged into
      euchromatin and facultative heterochromatin. Our results show that gene promoters
      have an open chromatin structure that is enhanced upon transcriptional activation
      but the Xa and the Xi have similar overall 30 nm chromatin fiber structures.
      Therefore, the formation of facultative heterochromatin is dependent on factors
      that act at a level above the 30 nm fiber and transcription does not alter bulk
      chromatin fiber structures. However, large-scale chromatin structures on Xa are
      decondensed compared with the Xi and transcription inhibition is sufficient to
      promote large-scale chromatin compaction. We show a link between transcription
      and large-scale chromatin packaging independent of the bulk 30 nm chromatin fiber
      and propose that transcription, not the global compaction of 30 nm chromatin
      fibers, determines the cytological appearance of large-scale chromatin
      structures.

PMID- 21070967
TI  - Crosstalk between mRNA 3' end processing and transcription initiation.
AB  - Transcription and mRNA maturation are interdependent events. Although stimulatory
      connections between these processes within the same round of transcription are
      well described, functional coupling between separate transcription cycles remains
      elusive. Comparing time-resolved transcription profiles of single-copy integrated
      beta-globin gene variants, we demonstrate that a polyadenylation site mutation
      decreases transcription initiation of the same gene. Upon depletion of the 3' end
      processing and transcription termination factor PCF11, endogenous genes exhibit a
      similar phenotype. Readthrough RNA polymerase II (RNAPII) engaged on
      polyadenylation site-mutated transcription units sequester the transcription
      initiation/elongation factors TBP, TFIIB and CDK9, leading to their depletion at
      the promoter. Additionally, high levels of TBP and TFIIB appear inside the gene
      body, and Ser2-phosphorylated RNAPII accumulates at the promoter. Our data
      demonstrate that 3' end formation stimulates transcription initiation and suggest
      that coordinated recycling of factors from a gene terminator back to the promoter
      is essential for sustaining continued transcription.

PMID- 21070968
TI  - Multiple mRNA decapping enzymes in mammalian cells.
AB  - Regulation of RNA degradation plays an important role in the control of gene
      expression. One mechanism of eukaryotic mRNA decay proceeds through an initial
      deadenylation followed by 5' end decapping and exonucleolytic decay. Dcp2 is
      currently believed to be the only cytoplasmic decapping enzyme responsible for
      decapping of all mRNAs. Here we report that Dcp2 protein modestly contributes to
      bulk mRNA decay and surprisingly is not detectable in a subset of mouse and human
      tissues. Consistent with these findings, a hypomorphic knockout of Dcp2 had no
      adverse consequences in mice. In contrast, the previously reported Xenopus
      nucleolar decapping enzyme, Nudt16, is an ubiquitous cytoplasmic decapping enzyme
      in mammalian cells. Like Dcp2, Nudt16 also regulates the stability of a subset of
      mRNAs including a member of the motin family of proteins involved in
      angiogenesis, Angiomotin-like 2. These data demonstrate mammalian cells possess
      multiple mRNA decapping enzymes, including Nudt16 to regulate mRNA turnover.

PMID- 21070969
TI  - WD40 repeat propellers define a ubiquitin-binding domain that regulates turnover
      of F box proteins.
AB  - WD40-repeat beta-propellers are found in a wide range of proteins involved in
      distinct biological activities. We define a large subset of WD40 beta-propellers
      as a class of ubiquitin-binding domains. Using the beta-propeller from Doa1/Ufd3
      as a paradigm, we find the conserved top surface of the Doa1 beta-propeller binds
      the hydrophobic patch of ubiquitin centered on residues I44, L8, and V70.
      Mutations that disrupt ubiquitin binding abrogate Doa1 function, demonstrating
      the importance of this interaction. We further demonstrate that WD40 beta
      propellers from a functionally diverse set of proteins bind ubiquitin in a
      similar fashion. This set includes members of the F box family of SCF ubiquitin
      E3 ligase adaptors. Using mutants defective in binding, we find that ubiquitin
      interaction by the F box protein Cdc4 promotes its autoubiquitination and
      turnover. Collectively, our results reveal a molecular mechanism that may account
      for how ubiquitin controls a broad spectrum of cellular activities.

PMID- 21070970
TI  - Psh1 is an E3 ubiquitin ligase that targets the centromeric histone variant Cse4.
AB  - Cse4 is a variant of histone H3 that is incorporated into a single nucleosome at
      each centromere in budding yeast. We have discovered an E3 ubiquitin ligase,
      called Psh1, which controls the cellular level of Cse4 via ubiquitylation and
      proteolysis. The activity of Psh1 is dependent on both its RING and zinc finger
      domains. We demonstrate the specificity of the ubiquitylation activity of Psh1
      toward Cse4 in vitro and map the sites of ubiquitylation. Mutation of key lysines
      prevents ubiquitylation of Cse4 by Psh1 in vitro and stabilizes Cse4 in vivo.
      While deletion of Psh1 stabilizes Cse4, elimination of the Cse4-specific
      chaperone Scm3 destabilizes Cse4, and the addition of Scm3 to the Psh1-Cse4
      ubiquitylation reaction prevents Cse4 ubiquitylation, together suggesting Scm3
      may protect Cse4 from ubiquitylation. Without Psh1, Cse4 overexpression is toxic
      and Cse4 is found at ectopic locations. Our results suggest Psh1 functions to
      prevent the mislocalization of Cse4.

PMID- 21070971
TI  - An E3 ubiquitin ligase prevents ectopic localization of the centromeric histone
      H3 variant via the centromere targeting domain.
AB  - Proper centromere function is critical to maintain genomic stability and to
      prevent aneuploidy, a hallmark of tumors and birth defects. A conserved feature
      of all eukaryotic centromeres is an essential histone H3 variant called CENP-A
      that requires a centromere targeting domain (CATD) for its localization. Although
      proteolysis prevents CENP-A from mislocalizing to euchromatin, regulatory factors
      have not been identified. Here, we identify an E3 ubiquitin ligase called Psh1
      that leads to the degradation of Cse4, the budding yeast CENP-A homolog. Cse4
      overexpression is toxic to psh1Delta cells and results in euchromatic
      localization. Strikingly, the Cse4 CATD is a key regulator of its stability and
      helps Psh1 discriminate Cse4 from histone H3. Taken together, we propose that the
      CATD has a previously unknown role in maintaining the exclusive localization of
      Cse4 by preventing its mislocalization to euchromatin via Psh1-mediated
      degradation.

PMID- 21070972
TI  - A stress-responsive system for mitochondrial protein degradation.
AB  - We show that Ydr049 (renamed VCP/Cdc48-associated mitochondrial stress-responsive
      -Vms1), a member of an unstudied pan-eukaryotic protein family, translocates from
      the cytosol to mitochondria upon mitochondrial stress. Cells lacking Vms1 show
      progressive mitochondrial failure, hypersensitivity to oxidative stress, and
      decreased chronological life span. Both yeast and mammalian Vms1 stably interact
      with Cdc48/VCP/p97, a component of the ubiquitin/proteasome system with a well
      defined role in endoplasmic reticulum-associated protein degradation (ERAD),
      wherein misfolded ER proteins are degraded in the cytosol. We show that oxidative
      stress triggers mitochondrial localization of Cdc48 and this is dependent on
      Vms1. When this system is impaired by mutation of Vms1, ubiquitin-dependent
      mitochondrial protein degradation, mitochondrial respiratory function, and cell
      viability are compromised. We demonstrate that Vms1 is a required component of an
      evolutionarily conserved system for mitochondrial protein degradation, which is
      necessary to maintain mitochondrial, cellular, and organismal viability.

PMID- 21070973
TI  - BH3-triggered structural reorganization drives the activation of proapoptotic
      BAX.
AB  - BAX is a proapoptotic BCL-2 family member that lies dormant in the cytosol until
      converted into a killer protein in response to cellular stress. Having recently
      identified the elusive trigger site for direct BAX activation, we now delineate
      by NMR and biochemical methods the essential allosteric conformational changes
      that transform ligand-triggered BAX into a fully activated monomer capable of
      propagating its own activation. Upon BAX engagement by a triggering BH3 helix,
      the unstructured loop between alpha helices 1 and 2 is displaced, the carboxy
      terminal helix 9 is mobilized for membrane translocation, and the exposed BAX BH3
      domain propagates the death signal through an autoactivating interaction with the
      trigger site of inactive BAX monomers. Our structure-activity analysis of this
      seminal apoptotic process reveals pharmacologic opportunities to modulate cell
      death by interceding at key steps of the BAX activation pathway.

PMID- 21070975
TI  - A vote for nutrition.

PMID- 21070974
TI  - Phosphoinositides are essential coactivators for p21-activated kinase 1.
AB  - Phospholipid-enriched membranes such as the plasma membrane can serve as direct
      regulators of kinase signaling. Pak1 is involved in growth factor signaling at
      the plasma membrane, and its dysregulation is implicated in cancer. Pak1 adopts
      an autoinhibited conformation that is relieved upon binding to membrane-bound Rho
      GTPases Rac1 or Cdc42, but whether lipids also regulate Pak1 in vivo is unknown.
      We show here that phosphoinositides, particularly PIP(2), potentiate Rho-GTPase
      mediated Pak1 activity. A positively charged region of Pak1 binds to
      phosphoinositide-containing membranes, and this interaction is essential for
      membrane recruitment and activation of Pak1 in response to extracellular signals.
      Our results highlight an active role for lipids as allosteric regulators of Pak1
      and suggest that Pak1 is a "coincidence detector" whose activation depends on
      GTPases present in phosphoinositide-rich membranes. These findings expand the
      role of phosphoinositides in kinase signaling and suggest how altered
      phosphoinositide metabolism may upregulate Pak1 activity in cancer cells.

PMID- 21070976
TI  - I "Like"JNEB.

PMID- 21070977
TI  - Position of the American Dietetic Association, School Nutrition Association, and
      Society for Nutrition Education: comprehensive school nutrition services.
AB  - It is the position of the American Dietetic Association (ADA), School Nutrition
      Association (SNA), and Society for Nutrition Education (SNE) that comprehensive,
      integrated nutrition services in schools, kindergarten through grade 12, are an
      essential component of coordinated school health programs and will improve the
      nutritional status, health, and academic performance of our nation's children.
      Local school wellness policies may strengthen comprehensive nutrition services by
      encouraging multidisciplinary wellness teams, composed of school and community
      members, to work together in identifying local school needs, developing feasible
      strategies to address priority areas, and integrating comprehensive nutrition
      services with a coordinated school health program. This joint position paper
      affirms schools as an important partner in health promotion. To maximize the
      impact of school wellness policies on strengthening comprehensive, integrated
      nutrition services in schools nationwide, ADA, SNA, and SNE recommend specific
      strategies in the following key areas: nutrition education and promotion, food
      and nutrition programs available on the school campus, school-home-community
      partnerships, and nutrition-related health services.

PMID- 21070978
TI  - Food insecurity and food choices in rural older adults with diabetes receiving
      nutrition education via telemedicine.
AB  - OBJECTIVE: To evaluate differences between rural older adults with diabetes
      reporting the presence or absence of food insecurity with respect to meal
      planning, preparation, shopping, obesity, and glycemic control after receiving
      nutrition counseling through telemedicine. METHODS: Food insecurity data were
      obtained by telephone survey (n=74). Group differences for continuous variables
      were measured by t tests; categorical variables by Pearson chi-square tests.
      RESULTS: Participants reporting mild food insecurity (23%) had higher body mass
      index (35.5+/-7.1 kg/m2 vs 30.5+/-6.0 kg/m2, P=.01) and lower household incomes
      (P=.03) and were more likely to consider cost of ingredients in food preparation
      compared to food-secure participants (P=.03). Most purchased fresh produce (97%)
      and considered the dietitian's advice when purchasing food. Both groups report
      similar adherence to dietitians' advice and had similar glycemic control.
      CONCLUSIONS AND IMPLICATIONS: Strategies to address higher levels of obesity
      associated with food insecurity are needed.

PMID- 21070979
TI  - Portion size labeling and intended soft drink consumption: the impact of labeling
      format and size portfolio.
AB  - OBJECTIVE: To assess what portion size labeling format is most promising in
      helping consumers selecting appropriate soft drink sizes, and whether labeling
      impact depends on the size portfolio. METHODS: An experimental study was
      conducted in fast-food restaurants in which 2 labeling formats (ie, reference
      portion size and small/medium/large labels) were compared to a control condition,
      and 2 size ranges were assessed. The main outcome variable was participants'
      intended soft drink size choice. Stimulus material was presented through
      photographs. RESULTS: There was a statistical trend for reference portion size
      labeling increasing the likelihood to choose small sizes (n=158, odds ratio=2.55,
      P=.06, confidence interval: 0.84-7.70). CONCLUSIONS AND IMPLICATIONS: Reference
      portion size labeling is potentially most promising in reducing large portion
      size preferences. More research assessing the effectiveness of reference portion
      size labeling (combined with pricing strategies) on actual choices and
      consumption behavior in a realistic setting is recommended.

PMID- 21070980
TI  - Involving cultural institutions in the prevention of childhood obesity: the
      Boston Children's Museum's GoKids Project.

PMID- 21070981
TI  - Thymoma. Preface.

PMID- 21070982
TI  - Prediction of thymoma histology and stage by radiographic criteria.
AB  - Thymic epithelial tumors, such as thymomas and thymic carcinomas, are the most
      common primary neoplasms of the mediastinum. In 1999, the World Health
      Organization (WHO) proposed a consensus classification of thymic epithelial
      tumors based on the morphology of the epithelial cells and the ratio of
      lymphocytes to epithelial cells, which was revised in 2004. The latest
      classification system stratifies thymic epithelial tumors into six categories:
      types A, AB, B1, B2, B3, and thymic carcinoma. This article describes the
      prediction of thymoma histology and stage on the basis of radiographic criteria
      by reviewing the following: the WHO histologic classification of thymic
      epithelial tumors, the clinical staging of thymomas based on prognosis, and the
      radiographic appearance of thymomas according to the WHO histologic
      classification.

PMID- 21070983
TI  - Neuroendocrine tumors of the thymus.
AB  - Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that
      were misdiagnosed as thymomas until the 1970s, when they eventually acquired a
      distinct identity. No collective large series have been published so far, and
      information about clinical presentation, diagnosis, histology, and treatment is
      derived from analysis of the case series and case reports published over a long
      period. NETTs are more aggressive than their pulmonary and abdominal
      counterparts, presenting at a more advanced stage, often with distant metastases,
      and are associated with poor long-term survival. Most patients are symptomatic at
      presentation as a result of the local invasion. Twenty percent to 30% of the
      cases are associated with endocrine disorders, mostly Cushing syndrome and
      multiple endocrine neoplasia syndrome. There is no official staging system for
      these tumors and investigators rely on the Masaoka staging system used for
      thymomas. Histologically, 2 classification are used: the World Health
      Organization and the Armed Forces Institute of Pathology classifications.
      Histologically, most tumors show moderately to poorly differentiated histologic
      features, reflecting their aggressive clinical behavior. Surgery is the most
      effective treatment option, although the aggressiveness of the tumor often
      requires extensive resection. Chemotherapy and radiotherapy may be used either
      preoperatively or postoperatively, although the small number of patients does not
      allow the design of standard guidelines about optimal schedules and doses.
      Survival depends on stage at presentation, histologic degree of differentiation,
      associated endocrine syndromes, and resectability rate. Recurrences are frequent
      after surgery and may be locoregional or distant. Surgery is recommended when
      feasible in the treatment of locoregional recurrences.

PMID- 21070984
TI  - Thymic carcinoma: is it a separate entity? From molecular to clinical evidence.
AB  - The second edition of the World Health Organization (WHO) classification of
      thymic tumors (2004) has resumed the previous separation of thymic carcinomas
      (TCs) from thymomas. This "reseparation" was mainly based on new genetic data.
      Consequently, it is no longer recommended to label TCs as type C thymomas. TCs
      are very heterogeneous and comprise squamous, basaloid cell, mucoepidermoid,
      neuroendocrine, and many other subtypes. They resemble morphologic mimics in
      other organs and are labeled accordingly. However, only thymic squamous cell
      carcinomas (TSCCs) and lymphoepithelioma-like carcinomas are relatively common.
      For TSCCs, quite specific immunohistochemical markers (eg, CD5, CD70, CD117,
      CD205, FOXN1) and chromosomal gains and losses have been defined that help to
      distinguish TSCCs not only from malignant thymomas but also from pulmonary
      squamous cell carcinomas. Recognition of these differences is clinically
      important, because the prognosis of TSCC is better compared with the other TC
      subtypes and also compared with lung tumors. Considering the need to treat
      advanced TC more effectively, disparate findings in predictive molecular markers
      (eg, KIT mutations in TSCC, but not in thymomas) suggest that targeted treatments
      will have to be different in thymomas and TC. Preliminary data from single case
      collections and small treatment trials support this prediction.

PMID- 21070985
TI  - Immunohistochemistry of thymic epithelial tumors as a tool in translational
      research.
AB  - Due to their heterogeneity and infrequency, thymic epithelial cell tumors (TET)
      represent a diagnostic as well as a therapeutic problem. In the early stage of
      disease TET are usually cured by performing radical resections, whereas in
      advanced stages of disease they are usually radically unresectable from the
      beginning, and often show multiple relapses and/or intra- or extrathoracic
      metastases. Trained pathologists are required in TET diagnostics; awareness of
      the complexity of the mediastinum and of the differential diagnostic
      possibilities is mandatory. Immunohistochemical (IHC) studies play a fundamental
      role in oncologic surgical pathology. Among the many uses of IHC in cancer
      research, studies on a possible association between biomarker expression and
      treatment outcomes dominate the clinical translational research applications.
      This article reports on and discusses the role of IHC in diagnostic and
      translational research of TET.

PMID- 21070986
TI  - Management of myasthenic patients with thymoma.
AB  - Myasthenia gravis (MG) associated with thymomas differs from nonthymomatous MG,
      and thymomas associated with MG are also different from non-MG thymomas.
      According to the World Health Organization classification, the incidence of MG in
      thymomas was the highest in the subtypes B2, B1, and AB. Transsternal approach is
      still regarded as the gold standard for surgical treatment of thymomas. Less
      invasive techniques of thymectomy are promising, but it is too early to estimate
      their real oncological value. In the series including more than 100 patients, the
      prognosis for survival is better in patients with thymomas associated with MG
      than in those with non-MG thymomas, and the prognosis for patients with MG
      associated with thymoma is worse than that for patients with nonthymomatous MG.

PMID- 21070987
TI  - Management of stage I and II thymoma.
AB  - With a knowledgeable assessment of the clinical presentation and demographic and
      radiologic characteristics, most thymomas can be reliably identified
      preoperatively without the need for a biopsy. Surgery is the mainstay of
      treatment for stage I and II thymoma. The rate of complete resection is
      essentially 100% by open techniques, and recurrences are rare. A complete
      thymectomy via a sternotomy is the standard approach. Adjuvant radiotherapy after
      a complete resection does not appear to be of benefit. In the rare event of a
      recurrence, an aggressive approach should be taken with re-resection whenever
      possible.

PMID- 21070988
TI  - Minimally invasive and robotic-assisted thymus resection.
AB  - Thymectomy for thymoma has traditionally been performed through a transsternal
      approach because of the excellent exposure that that the median sternotomy
      provides. Minimally invasive alternatives, such as transcervical thymectomy,
      video-assisted thymectomy, and robotic thymectomy, have not been extensively
      evaluated for this disease process. It is uncertain which patients may benefit
      from minimally invasive approaches and data regarding the oncologic effectiveness
      of these techniques remains to be established. However, given the excellent
      capability of these techniques to perform a complete and extensive thymectomy,
      there does appear to be a role for minimally invasive thymectomy in the treatment
      of thymoma.

PMID- 21070989
TI  - Surgical management of stage III thymic tumors.
AB  - Thymic tumors are classified as stage III when they clearly invade the
      surrounding structures: pericardium, great vessels (superior vena cava,
      innominate veins, ascending aorta, and main pulmonary artery), lung parenchyma,
      phrenic nerves, and chest wall. Surgical treatment with or without induction
      therapy should always aim to complete resection removing en bloc all the involved
      structures. Also, extended procedures are justified because only R0 resection
      allows long-term survival.

PMID- 21070990
TI  - Stage IVA thymoma: patterns of spread and surgical management.
AB  - Stage IVA disease can be de novo disease or more commonly represent recurrent
      disease. The pleura is the most common site of relapse after thymoma resection.
      Local pleural disease is usually simply resected. This is usually combined with
      either induction or adjuvant chemotherapy. The ultimate extended surgery for
      advanced thymic tumors is an extrapleural pneumonectomy done for extensive
      pleural disease. This rarely performed operation is done for both stage IVA
      disease found at initial presentation and for recurrent disease as a salvage
      procedure. Again, these advanced patients with pleural spread are probably best
      managed by induction chemotherapy followed by resection.

PMID- 21070991
TI  - The role of radiotherapy in the management of thymic tumors.
AB  - Radiotherapy is a major therapeutic modality for thymic malignancies. The exact
      role of adjuvant radiotherapy after complete resection is still debated for stage
      II through III tumors. Histology or size, capsular invasion, and even molecular
      data may be included in the decision making. Radiotherapy may be recommended for
      stage III thymomas, thymic carcinoma, or after incomplete surgical resection.
      Combination with chemotherapy may be useful, and must be further evaluated using
      validated end points, including 5- and 10-year time-to-progression and overall
      survival. Several initiatives have been taken worldwide to launch collaborative
      studies in the field, including prospective trials specifically readdressing the
      role of radiotherapy for thymic malignancies.

PMID- 21070992
TI  - Chemotherapy for thymic tumors: induction, consolidation, palliation.
AB  - Although thymoma and thymic carcinoma are rare malignancies, they constitute a
      large proportion of tumors of the anterior mediastinum. Surgery forms the
      mainstay of therapy; however, thymic malignancies are sensitive to chemotherapy
      and radiation therapy also. Systemic chemotherapy is primarily used for treatment
      of metastatic or recurrent disease. Chemotherapy is also used as a component of
      multimodality treatment in the neoadjuvant setting with the aim of increasing the
      chances of achieving a complete surgical resection. In this article we outline
      various clinical trials that have been performed to evaluate the role of
      chemotherapy in the treatment of thymic malignancies.

PMID- 21070993
TI  - Targeted therapies for thymic malignancies.
AB  - Significant efforts have been made to dissect the molecular pathways involved in
      the carcinogenesis of thymic malignancies. Research is hampered by the rarity of
      the tumor, controversies about histopathologic classification, and the lack of
      established cell lines and animal models. Insights into the biology of these
      tumors have been made following anecdotal clinical responses to targeted
      therapies. This article reviews current knowledge about the molecular data that
      define molecular subsets and support the use of targeted therapies in thymic
      tumors.

PMID- 21070994
TI  - Published guidelines for management of thymoma.
AB  - Guidelines for treatment of thymoma are prevalent in US literature, and many have
      been published by organizations in the United Kingdom, Canada, and Japan. This
      article reviews these many guidelines and summarizes them for the reader.

PMID- 21070995
TI  - The need for organization and collaboration: establishing a thymoma registry.
AB  - Thymic epithelial tumors (TETs) are rare thoracic malignancies, with an overall
      incidence of 1.5 per million people. The TET Registry Project aims at federating
      an international network to provide a resource to support studies on the
      epidemiology and clinical management and monitoring some standards of clinical
      care of these tumors. Recorded data span all the specifications of the management
      of TET: paraneoplastic syndromes, histologic subtypes, diagnostic and staging
      issues, multimodal treatment strategies, and exceptional surgeries and therapies.
      Data collection for the registry is done both prospectively and retrospectively
      through different paths to allow the involvement of as many centers as possible,
      including data-sharing arrangements with some already established databases. This
      ambitious project implies the early setting of strong quality assurance measures
      looking at completeness, consistency, and accuracy of the data. These measures
      require a significant and long-term financial support that will also be free of
      possible sources of conflicts of interests.

PMID- 21070996
TI  - An alternative isovelocity surface model for quantitation of effective
      regurgitant orifice area in mitral regurgitation with an elongated orifice
      application to functional mitral regurgitation.
AB  - OBJECTIVES: The purpose of this study was to develop and test a simple,
      clinically practical alternative isovelocity surface (ISVS) model for calculating
      effective regurgitant orifice area (EROA) in mitral regurgitation (MR) when the
      regurgitant orifice is elongated, such as in functional MR. BACKGROUND: Clinical
      experience and 3-dimensional imaging suggest that the traditional hemispheric
      ISVS model used in the conventional proximal isovelocity surface area (PISA)
      calculation is invalid in certain MR cases and can cause erroneous EROA values.
      METHODS: Our ISVS model consisted of 3 sections of equal radius (R): a
      cylindrical midsection of length (L) positioned between 2 hemispheroidal end
      sections. Total ISVS area (T(S)) is equal to 2piR(2) + piLR and EROA is equal to
      (V(N/)V(CW))T(S), where V(N) is the flow velocity crossing perpendicular to the
      ISVS, and V(CW) is the peak MR jet velocity by continuous-wave Doppler. This EROA
      was corrected for any obtuse angle, theta formed by tented leaflets, by
      multiplying T(S) by a planar factor, (theta/180) or a combination of this planar
      factor for the cylindrical midsection and the solid-angle factor, 1-cos(theta/2),
      for the 2 spheroidal end sections. In 24 cases of severe or 3+ functional MR, we
      calculated EROA using 3 traditional hemispheric surfaces and 3 alternative ISVS
      models that differed in the leaflet angle correction applied. Results were
      compared with continuity-based EROA using the standard mitral valve - aortic
      valve stroke volume method and with predictions based upon theoretical geometric
      considerations. RESULTS: The mean differences between continuity EROA and ISVS
      area-based EROA for no angle correction, planar correction, or combined angle
      correction were, respectively, 0.38, 0.32, and 0.28 cm(2) for the 3 spherical
      surface models and 0.17, 0.018, and -0.012 cm(2) for the 3 alternative 3-section
      ISVS models. The empiric EROA results with both the traditional spherical and
      alternative ISVS models agreed well with theoretical geometric predictions.
      CONCLUSIONS: The traditional spherical PISA model underestimates EROA in
      functional MR. For elongated MR orifices, an ISVS model that mirrors orifice
      shape yields more accurate EROA values. Correction to the ISVS area for obtuse
      leaflet angulation improves accuracy of EROA estimation.

PMID- 21070997
TI  - Increased pericardial fat volume measured from noncontrast CT predicts myocardial
      ischemia by SPECT.
AB  - OBJECTIVES: We evaluated the association between pericardial fat and myocardial
      ischemia for risk stratification. BACKGROUND: Pericardial fat volume (PFV) and
      thoracic fat volume (TFV) measured from noncontrast computed tomography (CT)
      performed for calculating coronary calcium score (CCS) are associated with
      increased CCS and risk for major adverse cardiovascular events. METHODS: From a
      cohort of 1,777 consecutive patients without previously known coronary artery
      disease (CAD) with noncontrast CT performed within 6 months of single photon
      emission computed tomography (SPECT), we compared 73 patients with ischemia by
      SPECT (cases) with 146 patients with normal SPECT (controls) matched by age,
      gender, CCS category, and symptoms and risk factors for CAD. TFV was
      automatically measured. Pericardial contours were manually defined within which
      fat voxels were automatically identified to compute PFV. Computer-assisted visual
      interpretation of SPECT was performed using standard 17-segment and 5-point score
      model; perfusion defect was quantified as summed stress score (SSS) and summed
      rest score (SRS). Ischemia was defined by: SSS - SRS >=4. Independent
      relationships of PFV and TFV to ischemia were examined. RESULTS: Cases had higher
      mean PFV (99.1 +/- 42.9 cm(3) vs. 80.1 +/- 31.8 cm(3), p = 0.0003) and TFV (196.1
      +/- 82.7 cm(3) vs. 160.8 +/- 72.1 cm(3), p = 0.001) and higher frequencies of PFV
      >125 cm(3) (22% vs. 8%, p = 0.004) and TFV >200 cm(3) (40% vs. 19%, p = 0.001)
      than controls. After adjustment for CCS, PFV and TFV remained the strongest
      predictors of ischemia (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.53
      to 5.52, p = 0.001 for each doubling of PFV; OR: 2.64, 95% CI: 1.48 to 4.72, p =
      0.001 for TFV). Receiver operating characteristic analysis showed that prediction
      of ischemia, as indicated by receiver-operator characteristic area under the
      curve, improved significantly when PFV or TFV was added to CCS (0.75 vs. 0.68, p
      = 0.04 for both). CONCLUSIONS: Pericardial fat was significantly associated with
      myocardial ischemia in patients without known CAD and may help improve risk
      assessment.

PMID- 21070998
TI  - Image quality and radiation exposure with a low tube voltage protocol for
      coronary CT angiography results of the PROTECTION II Trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate image quality and radiation
      dose using a 100 kVp tube voltage scan protocol compared with standard 120 kVp
      for coronary computed tomography angiography (CTA). BACKGROUND: Concerns have
      been raised about radiation exposure during coronary CTA. The use of a 100 kVp
      tube voltage scan protocol effectively lowers coronary CTA radiation dose
      compared with standard 120 kVp, but it is unknown whether image quality is
      maintained. METHODS: We enrolled 400 nonobese patients who underwent coronary
      CTA: 202 patients were randomly assigned to a 100 kVp protocol and 198 patients
      to a 120 kVp protocol. The primary end point was to demonstrate noninferiority in
      image quality with the 100 kVp protocol, which was assessed by a 4-point grading
      score (1 = nondiagnostic, 4 = excellent image quality). For the noninferiority
      analysis, a margin of -0.2 image quality score points for the difference between
      both scan protocols was pre-defined. Secondary end points included radiation dose
      and need for additional diagnostic tests during follow-up. RESULTS: The mean
      image quality scores in patients scanned with 100 kVp and 120 kVp were 3.30 +/-
      0.67 and 3.28 +/- 0.68, respectively (p = 0.742); image quality of the 100 kVp
      protocol was not inferior, as demonstrated by the 97.5% confidence interval of
      the difference, which did not cross the pre-defined noninferiority margin of 
      0.2. The 100 kVp protocol was associated with a 31% relative reduction in
      radiation exposure (dose-length product: 868 +/- 317 mGy * cm with 120 kVp vs.
      599 +/- 255 mGy * cm with 100 kVp; p < 0.0001). At 30-day follow-up, the need for
      additional diagnostic studies did not differ (13.4% vs. 19.2% for 100 kVp vs. 120
      kVp, respectively; p = 0.114). CONCLUSIONS: A coronary CTA protocol using 100 kVp
      tube voltage maintained image quality, but reduced radiation exposure by 31% as
      compared with the standard 120 kVp protocol. Thus, 100 kVp scan protocols should
      be considered for nonobese patients to keep radiation exposure as low as
      reasonably achievable. (Prospective Randomized Trial on Radiation Dose Estimates
      of Cardiac CT Angiography in Patients Scanned With a 100 kVp Protocol [PROTECTION
      II]; NCT00611780).

PMID- 21070999
TI  - Dose optimization in coronary CTA.

PMID- 21071000
TI  - Use of contrast enhancement and high-resolution 3D black-blood MRI to identify
      inflammation in atherosclerosis.
AB  - OBJECTIVES: We investigated the contributing factors for plaque enhancement and
      examined the relationships between regional contrast enhancement and the
      inflammatory activity of atherosclerotic plaques in an experimental rabbit model
      using contrast-enhanced high-resolution 3-dimensional (3D) black-blood magnetic
      resonance imaging (MRI) in comparison with histopathologic analysis. BACKGROUND:
      Inflammation plays a critical role in plaque initiation, progression, and
      disruption. As such, inflammation represents an emerging target for the treatment
      of atherosclerosis. MRI findings suggest that contrast agent-induced signal
      enhancement is associated with the degree of macrophage infiltration and
      neovessels that can be detected in plaque. METHODS: Ten atherosclerotic rabbits
      and 3 normal control rabbits underwent high-resolution 3D contrast-enhanced black
      blood MRI. Magnetic resonance images and the corresponding histopathologic
      sections were divided into 4 quadrants. Plaque composition was analyzed for each
      quadrant according to histopathologic criteria (percent of lipid-rich, fibrous,
      macrophage area and microvessel density) and imaging criteria (enhancement ratio
      [ER], ER = signal intensity(post)/signal intensity(pre)). Multiple linear
      regression analysis was performed to determine independent factors for plaque
      enhancement. RESULTS: A total of 62 noncalcified plaques (n = 248; 156 lipid-rich
      quadrants and 92 fibrous quadrants) were identified based on histopathologic
      analysis. Mean ER values were significantly higher in atherosclerotic vessel
      walls than in normal vessel walls (2.03 +/- 0.25 vs. 1.58 +/- 0.15; p = 0.017).
      The mean ER values were significantly higher in lipid-rich quadrants compared
      with the fibrous quadrants (2.14 +/- 0.31 vs. 1.84 +/- 0.21; p = 0.001). Mean ER
      values were significantly higher in macrophage-rich plaques compared with the
      macrophage-poor plaques (2.21 +/- 0.28 vs. 1.81 +/- 0.22; p = 0.001). Using
      multiple regression analysis, macrophage area and microvessel density were
      associated independently with ER values that reflected plaque enhancement (p <
      0.001). CONCLUSIONS: Contrast-enhanced high-resolution 3D black-blood MRI may be
      an efficient method to detect plaque inflammation.

PMID- 21071001
TI  - Noninvasive imaging of plaque inflammation: role of contrast-enhanced MRI.

PMID- 21071002
TI  - Improved near-term coronary artery disease risk classification with gated stress
      myocardial perfusion SPECT.
AB  - OBJECTIVES: We compared analytical approaches to estimate the added value of
      myocardial perfusion single-photon emission computed tomography (MPS) variables
      in estimating coronary artery disease (CAD) outcomes. BACKGROUND: Stress MPS
      markers of regional ischemia are strong estimators of prognosis. Evidence
      published to date has not compared analytical methods to establish the added
      value of stress MPS and to define a clinically meaningful approach to detect
      improve classification of risk. METHODS: A total of 4,575 patients were
      consecutively and prospectively enrolled in the Myoview Prognosis Registry.
      Multivariable Cox proportional hazards model were employed to estimate CAD death
      or myocardial infarction (MI). Risk reclassification methods were also
      calculated. RESULTS: In risk-adjusted models (including age, sex, presenting
      symptoms, stress type, CAD history, and risk factors), stress MPS ischemia, rest
      and post-stress left ventricular ejection fraction (LVEF) (all p < 0.0001) were
      all significant estimators of CAD death or MI. In this multivariable model, 34%
      of the model chi-square was contributed by MPS ischemia. In receiver-operating
      characteristic curve analysis, the area under the curve increased from 0.61 to
      0.66 when rest and post-stress LVEF were combined with pre-test CAD likelihood (p
      < 0.0001), increasing to 0.69 for MPS ischemia (p < 0.0001). The net
      reclassification improvement (NRI) by adding the Duke Treadmill Score (DTS) to a
      model including pre-test CAD likelihood was 0.112. The cost per NRI was $57 for
      the exercise test as compared with an office visit for risk stratification
      purposes. Further, the NRI by adding MPS ischemia to a model with the DTS and pre
      test CAD likelihood was 0.358. The cost per NRI was $615 for the stress MPS as
      compared with an exercise test. CONCLUSIONS: Stress-induced ischemia is
      independently predictive of near-term CAD outcomes. Analytical approaches that
      establish the reclassification of events provide a unique approach and may serve
      as a quality imaging metric for estimation of improved health outcomes for stress
      MPS as well as for comparison to other imaging modalities.

PMID- 21071003
TI  - Use of angiographic CT imaging in the cardiac catheterization laboratory for
      congenital heart disease.
AB  - OBJECTIVES: This study sought to retrospectively evaluate our initial experience
      using angiographic computed tomography (ACT) in a pediatric cardiac
      catheterization laboratory. BACKGROUND: ACT provides cross-sectional CT images
      from a rotational angiography run using a C-arm mounted flat-panel detector in
      the interventional suite. A 3-dimensional (3D) angiographic image can be created
      from the CT volume set and used in real time during the procedure. To our
      knowledge, its use has never previously been described for congenital heart
      disease. METHODS: 3D reconstructions were created and we retrospectively reviewed
      cases during our first year of ACT use. Images obtained were independently
      evaluated to determine their diagnostic utility. Radiation dose reduction
      protocols were defined using phantom testing and radiation dose calculation.
      RESULTS: ACT was used during 41 cardiac catheterizations in patients at a median
      age of 5.1 years (range: 0.4 to 58.8 years) for evaluation of: right ventricular
      outflow tract (RVOT)/central pulmonary arteries (PAs) in 20; cavopulmonary
      connection (CPC) in 11; pulmonary veins in 5; distal PAs in 4; and other
      locations in 5. Four subjects had 2 anatomic areas studied by ACT. The mean
      contrast volume for ACT was 1.2 +/- 0.4 ml/kg. Diagnostic-quality imaging was
      obtained in 71% of cases: 13/20 RVOT/central PAs; 9/11 CPC; 4/5 pulmonary veins;
      2/4 distal PAs; and 4/5 others. In 12 cases, ACT contributed to clinical outcomes
      beyond standard angiography. Radiation dose reduction protocols allowed ACT to be
      comparable in exposure to a standard biplane cineangiogram. CONCLUSIONS:
      Diagnostic-quality imaging can be obtained using ACT in 71% of cases without a
      significant increase in contrast or radiation exposure. In certain cases, ACT
      provides additional anatomic detail and may aid complex catheter manipulations.
      Future work is needed to continue to define applications of this new technology.

PMID- 21071004
TI  - Towards real-time intravascular endoscopic magnetic resonance imaging.
AB  - Fast, minimally invasive, high-resolution intravascular imaging is essential for
      identifying vascular pathological features and for developing novel diagnostic
      tools and treatments. Intravascular magnetic resonance imaging (MRI) with active
      internal probes offers high sensitivity to pathological features without ionizing
      radiation or the limited luminal views of conventional X-rays, but has been
      unable to provide a high-speed, high-resolution, endoscopic view. Herein, real
      time MRI endoscopy is introduced for performing MRI from a viewpoint
      intrinsically locked to a miniature active, internal transmitter-receiver in a
      clinical 3.0-T MRI scanner. Real-time MRI endoscopy at up to 2 frames/s depicts
      vascular wall morphological features, atherosclerosis, and calcification at 80 to
      300 MUm resolution during probe advancement through diseased human iliac artery
      specimens and atherosclerotic rabbit aortas in vivo. MRI endoscopy offers the
      potential for fast, minimally invasive, transluminal, high-resolution imaging of
      vascular disease on a common clinical platform suitable for evaluating and
      targeting atherosclerosis in both experimental and clinical settings.

PMID- 21071005
TI  - Getting closer for high-resolution vascular MRI.

PMID- 21071006
TI  - Echocardiography-guided biventricular pacemaker optimization.
AB  - Optimization of atrioventricular delay (AVD) and interventricular delay (VVD) in
      patients with a biventricular (Biv) pacemaker has been associated with
      improvement in cardiac output acutely, a reduction in heart failure symptoms, and
      improved exercise capacity. Several individual echocardiography (echo) Doppler
      parameters have been used for pacemaker optimization. In this review, pacemaker
      optimization based on echocardiographic evaluation of cardiac hemodynamics is
      presented. The goals of this paper are to discuss studies in echo-guided
      pacemaker optimization, provide a systemic guide to pacemaker interrogation and
      optimization in patients after Biv pacing who may have complex hemodynamic
      derangement, and finally, to discuss studies in optimization with exercise or
      atrial pacing. Case examples highlighting hemodynamic derangement in heart
      failure, tailoring of Biv pacemaker optimization to the underlying physiologic
      derangement, and its improvement with optimization are presented.

PMID- 21071008
TI  - Real-time 3D TEE allows optimized guidance of percutaneous edge-to-edge repair of
      the mitral valve.

PMID- 21071007
TI  - The year in molecular imaging.
AB  - Molecular imaging aims to enable personalized medicine via imaging-specific
      molecular and cellular targets that are relevant to the diagnosis and treatment
      of disease. By providing in vivo readouts of biological detail, molecular imaging
      complements traditional anatomical imaging modalities to allow: 1) visualization
      of important disease-modulating molecules and cells in vivo; 2) serial
      investigations to image evolutionary changes in disease attributes; and 3)
      evaluation of the in vivo molecular effects of biotherapeutics. The added
      information garnered by molecular imaging can improve risk assessment and
      prognosticative studies, this is of particular benefit in the management of
      cardiovascular disease (CVD).

PMID- 21071009
TI  - Real-time 3D TEE for multiperforated interatrial septum.

PMID- 21071010
TI  - Important echocardiographic features of takotsubo or stress-induced
      cardiomyopathy that can aid early diagnosis.

PMID- 21071011
TI  - Radiation exposure from cardiac computed tomography.

PMID- 21071014
TI  - Whither catheter-based intravascular magnetic resonance imaging of
      atherosclerosis?

PMID- 21071015
TI  - Postural stability effects of random vibration at the feet of construction
      workers in simulated elevation.
AB  - The risk of falls from height on a construction site increases under conditions
      which degrade workers' postural control. At elevation, workers depend heavily on
      sensory information from their feet to maintain balance. The study tested two
      hypotheses: "sensory enhancement"--sub-sensory (undetectable) random mechanical
      vibrations at the plantar surface of the feet can improve worker's balance at
      elevation; and "sensory suppression"--supra-sensory (detectable) random
      mechanical vibrations can have a degrading effect on balance in the same
      experimental settings. Six young (age 20-35) and six aging (age 45-60)
      construction workers were tested while standing in standard and semi-tandem
      postures on instrumented gel insoles. The insoles applied sub- or supra-sensory
      levels of random mechanical vibrations to the feet. The tests were conducted in a
      surround-screen virtual reality system, which simulated a narrow plank at
      elevation on a construction site. Upper body kinematics was assessed with a
      motion-measurement system. Postural stability effects were evaluated by
      conventional and statistical mechanics sway measures, as well as trunk angular
      displacement parameters. Analysis of variance did not confirm the "sensory
      enhancement" hypothesis, but provided evidence for the "sensory suppression"
      hypothesis. The supra-sensory vibration had a destabilizing effect, which was
      considerably stronger in the semi-tandem posture and affected most of the sway
      variables. Sensory suppression associated with elevated vibration levels on a
      construction site may increase the danger of losing balance. Construction workers
      at elevation, e.g., on a beam or narrow plank might be at increased risk of fall
      if they can detect vibrations under their feet. To reduce the possibility of
      losing balance, mechanical vibration to supporting structures used as
      walking/working surfaces should be minimized when performing construction tasks
      at elevation.

PMID- 21071016
TI  - Genetic influences on being processed through the criminal justice system:
      results from a sample of adoptees.
AB  - BACKGROUND: Behavioral genetic research has revealed that antisocial phenotypes
      are under genetic influence. This study examines whether genetic factors also
      affect the odds of being processed through the criminal justice system. METHODS:
      A sample of adoptees (n = 191-257) drawn from the National Longitudinal Study of
      Adolescent Health was analyzed. They self-reported on whether they had ever been
      arrested, sentenced to probation, incarcerated, and arrested multiple times.
      Assessments were also conducted of the criminal status of their biological
      parents. RESULTS: Adoptees who have a biological father or a biological mother
      who have been arrested previously are significantly more likely to be arrested,
      sentenced to probation, incarcerated, and arrested multiple times when compared
      with adoptees whose biological parents have not been arrested. CONCLUSIONS:
      Adoptees who are genetically predisposed to antisocial phenotypes are at risk for
      being formally processed through the criminal justice system.

PMID- 21071017
TI  - CD4 co-receptor dependent signaling promotes competency for re-stimulation
      induced cell death of effector T cells.
AB  - The elimination of activated T cells by FAS-mediated signaling is an important
      immunoregulatory mechanism used to maintain homeostasis and prevent tissue
      damage. T cell receptor-dependent signals are required to confer sensitivity to
      FAS-mediated re-stimulation-induced cell death (RICD), however, the nature of
      these signals is not well understood. In this report, we show, using T cells from
      CD4-deficient mice reconstituted with a tail-less CD4 transgene, that CD4
      dependent signaling events are a critical part of the competency signal required
      for RICD. This is in part due to defects in FAS receptor signaling complex
      formation as shown by decreased recruitment of FAS and caspase 8 into lipid rafts
      following antigen re-stimulation in the absence of CD4-dependent signals. In
      addition, in the absence of CD4-dependent signals, effector T cells have a
      selective defect in IL-2 secretion following peptide re-stimulation, while
      provision of exogenous IL-2 during re-stimulation partially restores
      susceptibility to RICD. Importantly, IL-2 production and proliferation after
      primary peptide stimulation is comparable between wild type and CD4-deficient T
      cells indicating that the requirement for CD4-dependent signaling events for IL-2
      production is developmentally regulated and is particularly critical in
      previously activated effector T cells. In total, our results indicate that CD4 co
      receptor dependent signaling events specifically regulate effector T cell
      survival and function. Further, these data suggest that CD4-dependent signaling
      events may protect against the decreased IL-2 production and resistance to cell
      death seen during chronic immune stimulation.

PMID- 21071019
TI  - Oxidative parameters of embryo culture media may predict treatment outcome in in
      vitro fertilization: a novel applicable tool for improving embryo selection.
AB  - OBJECTIVE: To examine whether the oxidative status of an individual embryo before
      transfer may predict chances of implantation. DESIGN: A prospective laboratory
      study. SETTING: An IVF unit in a university-affiliated hospital. PATIENT(S): One
      hundred thirty-three women undergoing IVF-ET treatment cycles. INTERVENTION(S):
      Before ET, 10 MUL of embryo culture medium was retrieved individually from each
      embryo and the oxidative status assessed by the thermochemiluminescence (TCL)
      analyzer. MAIN OUTCOME MEASURE(S): The occurrence of pregnancy. Two parameters
      were recorded: the TCL amplitude after 50 seconds (H1) and the TCL ratio. These
      were compared with demographic, clinical, and laboratory parameters and treatment
      outcome. All data underwent statistical analysis. RESULT(S): Altogether 284
      embryos were transferred in 133 ET cycles. Forty-one pregnancies occurred (31%).
      For embryos transferred after 72 hours (77 transfers), the highest H1 levels in
      each group of transferred embryos correlated with the occurrence of pregnancy.
      The combination of maximal intracohort H1 level <210 counts per second with a TCL
      ratio of <= 80% had a positive predictive value of 70.6% for the occurrence of
      pregnancy. CONCLUSION(S): The oxidative status of the early embryo in IVF is
      associated with the chances of implantation. Assessment of the oxidative status
      of embryos in culture media before transfer may serve as an applicable tool for
      improving embryo selection in light of the legal limitations of the number of
      transferred embryos allowed.

PMID- 21071020
TI  - Day 2 embryo transfer (ET) and day 3 ET afford similar reproductive outcomes in
      the poor responder.
AB  - A retrospective review of 237 initial, fresh nondonor IVF cycles in which all
      embryos generated during the cycle were transferred on either day 2 (n = 109) or
      day 3 (n = 128) were evaluated with regards to reproductive outcomes. Patients
      who underwent a day 2 ET had similar conception (18% vs. 16%; relative risk [RR],
      1.1; 95% confidence interval [CI], 0.64-1.95), clinical pregnancy (13% vs. 16%;
      RR, 0.8; 95% CI, 0.44-1.55), implantation (6% vs. 7%; RR, 0.9; 95% CI, 0.50
      1.68), and live-birth (10% vs. 16%; RR, 0.7; 95% CI, 0.32-1.29) rates as those
      who underwent a day 3 ET.

PMID- 21071018
TI  - Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro
      fertilization/intracytoplasmic sperm injection cycles.
AB  - To determine the impact of maternal metabolic state on oocyte development in
      women undergoing in vitro fertilization/intracytoplasmic sperm injection
      (IVF/ICSI), we retrospectively analyzed a cohort of women with PCOS undergoing
      IVF/ICSI from 2008-2009 in a university-based fertility center. We determined
      that women with PCOS and obesity have smaller oocytes than control subjects, and
      that when further subdivided by body mass index, both PCOS and obesity
      independently influence oocyte size.

PMID- 21071021
TI  - Testicular sperm from patients with obstructive and nonobstructive azoospermia:
      aneuploidy risk and reproductive prognosis using testicular sperm from fertile
      donors as control samples.
AB  - OBJECTIVE: To establish a baseline incidence of chromosomal abnormalities in
      testicular sperm of fertile men and to determine the best control sample for
      comparisons with azoospermic males to estimate their reproductive prognosis.
      DESIGN: Prospective study. SETTING: Infertility clinic. PATIENT(S): Sixteen
      obstructive azoospermic (OA) and 19 nonobstructive azoospermic patients (NOA).
      Control samples were ejaculated sperm from ten fertile donors and testicular
      sperm from ten other fertile donors. INTERVENTION(S): Fluorescence in situ
      hybridization (FISH) in sperm. MAIN OUTCOME MEASURE(S): Sperm numerical
      abnormalities for chromosomes 13, 18, 21, X, and Y; ongoing implantation and
      pregnancy rates in intracytoplasmic sperm injection (ICSI) cycles. RESULT(S): In
      control samples, testicular sperm showed higher incidences of diploidy (0.27% vs.
      0.10%) and disomy for chromosomes 13 (0.16% vs. 0.07%), 21 (0.25% vs. 0.12%), and
      sex chromosomes (0.34% vs. 0.21%) than ejaculated sperm. Comparisons with
      ejaculated control samples showed 12.5% OA and 68.4% NOA patients having
      significantly higher incidence of sperm chromosomal abnormalities. Compared with
      testicular control subjects, fewer OA (6.3%) and NOA (42.1%) patients had
      chromosomally abnormal sperm. NOA patients had lower ongoing implantation and
      pregnancy rates than OA patients, particularly those with abnormal FISH compared
      with testicular control samples. CONCLUSION(S): Sperm FISH analysis using
      testicular sperm control samples better identifies NOA patients with a lower
      likelihood of reproductive success.

PMID- 21071022
TI  - Effect of gonadotropins on dynamic events and global deoxyribonucleic acid
      methylation during in vitro maturation of oocytes: an animal model.
AB  - Although the redistributions of mitochondria and cortical granules and global DNA
      methylation status were not altered in a dose-response manner, high dosages of
      gonadotropin induced spindle and chromosomal abnormalities. The present study
      highlights the importance of judicious use of gonadotropins and can be applied to
      clinical stimulation protocols to reduce the potential risks.

PMID- 21071023
TI  - Parental karyotype may reveal the source of a pregnancy loss even in the presence
      of a reportedly euploid fetal karyotype.
AB  - OBJECTIVE: To present a case of a fetal loss in which a normal fetal karyotype
      was obtained by banding studies. Identification of an abnormal maternal karyotype
      prompted subsequent reanalysis using fluorescence in situ hybridization (FISH).
      DESIGN: Case report. SETTING: University-affiliated IVF center. PATIENT(S): A 32
      year-old woman, G1 P0, underwent a fetal loss at 8 weeks, and a suction curettage
      was performed. The patient had a previous first-trimester loss. INTERVENTION(S):
      The fetal tissue was evaluated by banding studies and found to be normal.
      Parental karyotyping was performed, and the fetal tissue was reanalyzed by FISH.
      MAIN OUTCOME MEASURE(S): Analysis of fetal karyotype by targeted FISH. RESULT(S):
      Maternal karyotype demonstrated a translocation [46,XX, t(8;10)(q24.3:q25.2)].
      The fetal tissue was reanalyzed by FISH, and a segment of chromosome 10 was found
      on chromosome 8. CONCLUSION(S): A normal fetal karyotype, as measured by banding,
      does not exclude a genetic etiology for pregnancy loss. In this case, maternal
      translocation prompted the genetics laboratory to search for a small segment of
      translocated extra chromosomal material. This demonstrated that despite the
      finding of a normal fetal karyotype, in some cases parental karyotyping may have
      value.

PMID- 21071024
TI  - Questioning patients about their adolescent history can identify markers
      associated with deep infiltrating endometriosis.
AB  - OBJECTIVE: To investigate whether the clinical history, particularly of the
      adolescence period, contains markers of deeply infiltrating endometriosis (DIE).
      DESIGN: Cross-sectional study. SETTING: Universitary tertiary referral center.
      PATIENT(S): Two hundred twenty-nine patients operated on for endometriosis.
      Endometriotic lesions were histologically confirmed as non-DIE (superficial
      peritoneal endometriosis and/or ovarian endometriomas) (n = 131) or DIE (n = 98).
      INTERVENTION(S): Surgical excision of endometriotic lesions with pathological
      analysis of each specimens. MAIN OUTCOME MEASURE(S): Epidemiological data, pelvic
      pain scores, family history of endometriosis, absenteeism from school during
      menstruation, oral contraceptive (OC) pill use. RESULT(S): Patients with DIE had
      significantly more positive family history of endometriosis (odds ratio [OR] =
      3.2; 95% confidence interval [CI]: 1.2-8.8) and more absenteeism from school
      during menstruation (OR = 1.7; 95% CI: 1-3). The OC pill use for treating severe
      primary dysmenorrhea was more frequent in patients with DIE (OR = 4.5; 95% CI:
      1.9-10.4). Duration of OC pill use for severe primary dysmenorrhea was longer in
      patients with DIE (8.4 +/- 4.7 years vs. 5.1 +/- 3.8 years). There was a higher
      incidence of OC pill use for severe primary dysmenorrhea before 18 years of age
      in patients with DIE (OR = 4.2; 95% CI: 1.8-10.0). CONCLUSION(S): The knowledge
      of adolescent period history can identify markers that are associated with DIE in
      patients undergoing surgery for endometriosis.

PMID- 21071025
TI  - Concentrations of stromal cell-derived factor-1 and vascular endothelial growth
      factor in relation to the diameter of human follicles.
AB  - OBJECTIVE: To determine the concentrations of stromal cell-derived factor-1 (SDF
      1/CXCL12) and vascular endothelial growth factor (VEGF) in individual human
      preovulatory follicles in relation to their diameter or volume for clarifying the
      role of these molecules in folliculogenesis. DESIGN: Prospective study. SETTING:
      Research laboratory at Kansai Medical University. PATIENT(S): Twenty-seven women
      undergoing IVF. INTERVENTION(S): Follicular fluid (FF) was collected from
      individual follicles. A total of 373 follicles were analyzed. MAIN OUTCOME
      MEASURE(S): The concentrations of SDF-1 and VEGF in FF and oocyte recovery rates.
      RESULT(S): The concentrations of SDF-1 and VEGF in follicles with a diameter <=
      14 mm were significantly lower than those in follicles with a diameter >= 15 mm.
      The concentrations of SDF-1 and VEGF in FF increased with follicular diameters or
      volume, with concentrations peaking in follicles with a diameter of 18-20 mm or a
      volume of 3.6-5.0 mL. Furthermore, we found that there exists a positive
      correlation between the concentrations of SDF-1 and VEGF in FF from follicles <=
      20 mm in diameter. The oocyte recovery rates increased with concentrations of SDF
      1 and VEGF in FF. CONCLUSION(S): Our data suggest that SDF-1, as well as VEGF,
      may play an important role in follicular growth and development.

PMID- 21071026
TI  - Effect of vitrification and thawing on human oocyte ATP concentration.
AB  - Vitrification/thawing has a significant negative impact on oocyte ATP
      concentration. However, incubating oocytes up to 180 minutes after thawing
      allowed oocytes to regain some ATP level.

PMID- 21071027
TI  - Trans-fatty acid levels in sperm are associated with sperm concentration among
      men from an infertility clinic.
AB  - We measured the sperm fatty acid composition using gas chromatography in
      anonymized semen samples of 33 men undergoing infertility evaluation at an
      academic medical center. Trans-fatty acids were present in human sperm and were
      related inversely to sperm concentration (r = -0.44).

PMID- 21071028
TI  - How do nurses make decisions?

PMID- 21071029
TI  - Protective effects of dehydroepiandrosterone on atherosclerosis in ovariectomized
      rabbits via alleviating inflammatory injury in endothelial cells.
AB  - OBJECTIVE: The risk for atherosclerosis is increased in postmenopausal women.
      Dehydroepiandrosterone (DHEA) is postulated to have anti-atherogenic properties,
      but the mechanism remains unclear. The aim of this study was to elucidate the
      protective effect of DHEA on atherosclerosis in ovariectomized rabbits. METHODS:
      The lipid status and atherosclerotic lesions were examined in vivo in
      ovariectomized rabbits. The effects of DHEA on expression of inflammatory
      molecules were evaluated in vitro, such as nitric oxide (NO), malondialdehyde
      (MDA), monocyte chemoattractant protein-1 (MCP-1), adhesion molecules (ICAM-1,
      VCAM-1 and E-selectin) in the human umbilical vein endothelial cells (HUVECs)
      injured by oxidized low-density lipoproteins (ox-LDL). The adhesion of the
      monocytic U937 cells to HUVECs was treated with supernatants of ox-LDL treated
      HUVECs with or without DHEA, and then the expressions of CCR2, LFA-1, VLA-4 were
      analyzed in U937 cells. The HUVECs with or without LPS treatment were then
      treated with DHEA, and NF-kappaB activity was measured by luciferase activity.
      RESULTS: DHEA administration alleviates efficiently the early pathologic damage
      of atherosclerosis, increases the serum NO level, and up-regulates the
      endothelial cell estrogen receptor (ER) expression of ovariectomized rabbits.
      DHEA in vitro significantly promotes NO synthesis, suppresses MDA and MCP-1
      secretion of endothelial cells, and decreases ICAM-1, VCAM-1 and E-selectin
      expression in HUVECs; neither selective ERalpha antagonist (methyl-piperidino
      pyrazole, MPP) nor ERbeta antagonist (R,R-tetrahydrochrysene, R,RTHC) can abolish
      these effects. Furthermore, DHEA reduces CCR2, LFA-1 and VLA-4 expression in U937
      cells, which in turn inhibits the adherence of monocytes to the injured
      endothelial cells. DHEA significantly decreased the LPS-induced NF-kappaB
      transcription. CONCLUSIONS: Our findings suggest that DHEA can alleviate
      inflammation in endothelial cells. The effects of DHEA on endothelial cells are
      independent of ERalpha or ERbeta pathway, but at least in part, through
      suppression of NF-kappaB activity, which protects from atherosclerosis triggered
      by monocyte adherence.

PMID- 21071030
TI  - Challenges to bone formation in spinal fusion.
AB  - Spinal arthrodesis continues to expand in clinical indications and surgical
      practice. Despite a century of study, failure of bone formation or pseudarthrosis
      can occur in individual patients with debilitating clinical symptoms. Here we
      review biological and technical aspects of spinal fusion under active
      investigation, describe relevant biomechanics in health and disease, and identify
      the possibilities and limitations of translational animal models. The purpose of
      this article is to foster collaborative efforts with researchers who model bone
      hierarchy. The induction of heterotopic osteosynthesis requires a complex balance
      of biologic factors and operative technique to achieve successful fusion.
      Anatomical considerations of each spinal region including blood supply,
      osteology, and biomechanics predispose a fusion site to robust or insufficient
      bone formation. Careful preparation of the fusion site and appropriate selection
      of graft materials remains critical but is sometimes guided by conflicting
      evidence from the long-bone literature. Modern techniques of graft site
      preparation and instrumentation have evolved for every segment of the vertebral
      column. Despite validated biomechanical studies of modern instrumentation, a
      correlation with superior clinical outcomes is difficult to demonstrate. In many
      cases, adjuvant biologic therapies with allograft and synthetic cages have been
      used successfully to reproduce the enhancement of fusion rates observed with
      cancellous and tricortical autograft. Current areas of investigation comprise
      materials science, stem cell therapies, recombinant growth factors, scaffolds and
      biologic delivery systems, and minimally invasive surgical techniques to optimize
      the biologic response to intervention. Diverse animal models are required to
      approach the breadth of spinal pathology and novel therapeutics.

PMID- 21071031
TI  - Variations in morphological and biomechanical indices at the distal radius in
      subjects with identical BMD.
AB  - Determination of osteoporotic status is based primarily on areal bone mineral
      density (aBMD) obtained through dual X-ray absorptiometry (DXA). However, many
      fractures occur in patients with T-scores above the WHO threshold of
      osteoporosis, in part because DXA measures are insensitive to biomechanically
      important alterations in bone quality. The goal of this study was to determine-
      within groups of subjects with identical radius aBMD values--the extant variation
      in densitometric, geometric, microstructural, and biomechanical parameters. High
      resolution peripheral quantitative computed tomography (HR-pQCT) and DXA radius
      data from males and females spanning large ranges in age, osteoporotic status,
      and anthropometrics were compiled. 262 distal radius datasets were processed for
      this study. HR-pQCT scans were analyzed according to the manufacturer's standard
      clinical protocol to quantify densitometric, geometric, and microstructural
      indices. Micro-finite element analysis was performed to calculate biomechanical
      indices. Factor of risk of wrist fracture was calculated. Simulated aBMD
      calculated from HR-pQCT data was used to group scans for evaluation of variation
      in quantified indices. Indices reflecting the greatest variation within aBMD
      level were BMD in the central portion of the trabecular compartment (max CV 142),
      trabecular heterogeneity (max CV 90), and intra-cortical porosity (max CV 151).
      Of the biomechanical indices, cortical load fraction had the greatest variation
      (max CV 38). Substantial variations in indices reflecting density, structure, and
      biomechanical competence exist among subjects with identical aBMD levels. Overlap
      of these indices among osteoporotic status groups reflects the reported incidence
      of osteoporotic fracture in subjects classified as osteopenic or normal.

PMID- 21071032
TI  - A direct Capillary Liquid Chromatography with electrochemical detection method
      for determination of phenols in water samples.
AB  - A fast and direct method based on the use of Capillary Liquid Chromatography (LC)
      with electrochemical (EC) detection has been described for phenols pollutants in
      water samples. Concretely, phenol, o-cresol, 2-chlorophenol and bisphenol A have
      been selected as target analytes. The combination of Capillary LC with EC
      detection avoided the necessity of preconcentration steps typically used in
      environmental analysis. The sample injected volume was 2MUL. The achieved
      detection limits were between 1 and 2MUg/L and the linear dynamic range was up to
      50MUg/L for all studied phenols. The precision and uncertainty were satisfactory.
      The analysis time per sample was 10min. The proposed procedure has been proved
      useful for treated waters.

PMID- 21071033
TI  - Potential of nanoparticles in sample preparation.
AB  - The paper presents a general overview of the use of nanoparticles to perform
      sample preparation. In this way the main uses of nanoparticles to carry out solid
      phase extraction, solid phase microextraction, liquid-liquid extraction and
      filtration techniques are described for a wide range of nanoparticles including
      carbon nanoparticles, metallic, silica and molecular imprinted polymer
      nanoparticles.

PMID- 21071034
TI  - Comparison of electrospray ionization, atmospheric pressure photoionization, and
      anion attachment atmospheric pressure photoionization for the analysis of
      hexabromocyclododecane enantiomers in environmental samples.
AB  - Anion attachment atmospheric pressure photoionization (AA-APPI) has been
      suggested as a means of expanding the range of compounds that may be analyzed by
      LC-MS, and has been found to enhance the ionization of some macromolecules (e.g.,
      peptides, polymers) that were unable to be ionized by other techniques. In this
      study, AA-APPI was compared to APPI, using hexabromocyclododecane (HBCD)
      enantiomers as a model compound, to provide proof of principle of the use of AA
      APPI for small molecule analysis. The use of AA-APPI, with 1,4-dibromobutane in
      toluene as a bromide source, offered increased sensitivity and lower limits of
      detection than APPI. Minimal matrix effects were found with AA-APPI in sediment
      extracts spiked with HBCD post-extraction, with less than a 6% enhancement in the
      ion signal. Furthermore, enantiomer fractions of HBCD enantiomers were racemic in
      spiked sediment extracts, in contrast to the more commonly used technique of
      electrospray ionization, for which matrix effects caused ion signal modification
      to cause non-racemic measurement artifacts. The use of AA-APPI offers a simple
      means of further extending the range of compounds ionizable by AA-APPI while
      maintaining minimal matrix effects.

PMID- 21071035
TI  - Determination of perfluorochemicals in biological, environmental and food samples
      by an automated on-line solid phase extraction ultra high performance liquid
      chromatography tandem mass spectrometry method.
AB  - A rapid on-line solid phase extraction ultra high performance liquid
      chromatography tandem mass spectrometry method was developed for the
      identification and quantitation of nine perfluorinated compounds in matrices of
      environmental, biological and food interest. Pre-treatment, solid phase
      extraction, chromatographic and mass detection conditions were optimised, in
      order to apply the whole methodology to the analysis of different matrices.
      Particular attention was devoted to the evaluation of matrix effect and the
      correlated phenomena of ion enhancement or suppression in mass spectrometry
      detection. LOD and LOQ range from 3 to 15ngL(-1) and from 10 to 50ngL(-1),
      respectively. Method detection limits (MDLs) were also calculated for each kind
      of matrix. The recovery, evaluated for each analyte, does not depend on analyte
      concentration in the explored concentration range: average R-% values are always
      greater than 82.9%. In the whole, the results obtained for samples of river
      waters, blood serum, blood plasma, and fish confirm the ubiquitous presence of
      perfluorinated compounds, as recently denounced by many sources.

PMID- 21071037
TI  - Investigation of Yb(III)-PVC membrane interfacial interaction by semiempirical
      PM6/SPARKLE method based on 1,10-phenanthroline-5,6-dione as a suitable neutral
      ionophore.
AB  - To predict the selectivity of Yb(III)-PVC membrane, the semiempirical PM6/SPARKLE
      method was used to investigate the binding of Yb(III) and other cations to 1,10
      phenanthroline-5,6-dione (PDO). The study has shown that the chelating ligand,
      PDO, is selectively coordinated to Yb(III) at two coordination sites involving
      the pyridylic nitrogen atoms in the interface of membrane/solution. The membrane
      was used as a potentiometric Yb sensor, based on PDO as an ionophore, sodium
      tetraphenyl borate (NaTBP) as a lipophilic ionic additive, and tributyl phosphate
      (TBP) as a plasticizer. The electrode had a good Nernstian response for Yb(III)
      ions over a wide concentration range from 5*10(-6) to 1*10(-2)M and a detection
      limit of 5.7*10(-7)M with a slope of 19.7+/-0.2mV/decade in a pH range of 4.0
      12.0. The sensor had a very fast response time of less than 5s over the whole
      concentration range and can be used over a period of 6wk without any significant
      divergence in potentials.

PMID- 21071036
TI  - High-performance TiO(2) from Baker's yeast.
AB  - Based on the biomineralization assembly concept, a biomimetic approach has been
      developed to synthesize high-performance mesoporous TiO(2). The key step of this
      approach is to apply Baker's yeast cells as biotemplates for deriving the
      hierarchically ordered mesoporous anatase structure. The mechanism of formation
      of the yeast-TiO(2) is revealed by characterizing its morphology, microstructure,
      and chemical composition. The yeast-TiO(2) exhibits outstanding photocatalytic
      performance. Under visible-light irradiation, the removal efficiency of chemical
      oxygen demand (COD) and color of the paper industry wastewater has reached 80.3%
      and nearly 100%, respectively. The approach may open new vistas for fabricating
      advanced mesoporous materials under ambient condition.

PMID- 21071038
TI  - Complexation of cationic polyelectrolyte with anionic phospholipid vesicles:
      Concentration, molecular weight and salt effects.
AB  - The influence of cationic poly(diallyldimethylammonium chloride) on the
      morphology and phase behavior of anionic phospholipid vesicles was investigated
      using differential scanning calorimetry, fluorescent microscopy and light
      scattering technique. A wide range of polymer concentration has been examined for
      the first time. The polycation can bind electrostatically to the vesicles to
      compensate, neutralize and reverse the vesicular charge, depending on the molar
      ratio of cationic to anionic group R. For R<1, charge compensation weakened the
      electrostatic repulsion between the lipid molecules, leading to formation of
      polymer-modified vesicles, each with an increased number of bilayers. The bilayer
      exhibits a rising main phase transition temperature from a gel to liquid
      crystalline state. This behavior persisted until R~1 around the neutralization
      condition, where the complexes became largest and precipitate. With R>1, charge
      reversal took place, the complex size reduced. Interestingly, the main phase
      transition temperature was found for the first time to shift back towards the
      original value in the absence of polymer for large enough R. Although the thermal
      behavior was nearly independent of the polymer molecular weight, the complex
      morphology could be different.

PMID- 21071039
TI  - Schwann cell-like remyelination following transplantation of human umbilical cord
      blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord
      injury.
AB  - Human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) have
      significant therapeutic potential in cell-based therapies following spinal cord
      injury (SCI). To evaluate this potential, we conducted our preliminary
      investigations on the remyelination of injured spinal cords with hUCB-MSC
      transplantations and we observed its long term effects on dogs with SCI. Of the
      ten injured dogs, seven were transplanted with hUCB-MSCs 1 week after SCI,
      whereas the remaining three dogs were not transplanted. Two transplanted dogs
      died over the first month after transplantation because of urinary tract
      infection, bedsores and sepsis. The SCI dogs showed no improvement in motor and
      sensory functions and their urinary dysfunction persisted until they were
      euthanized (from 3 months to 1 year) while hind-limb recovery in 4 dogs among the
      five transplanted dogs was significantly improved. In the recovered dogs,
      functional recovery was sustained for three years following transplantation.
      Histological results from five transplanted dogs showed that many axons were
      remyelinated by P0-positive myelin sheaths after transplantation. Our results
      suggest that transplantation of hUCB-derived MSCs may have beneficial therapeutic
      effects. Furthermore, histological results provided the first in vivo evidence
      that hUCB-MSCs are able to enhance the remyelination of peripheral-type myelin
      sheaths following SCI.

PMID- 21071040
TI  - Optimal care of patients with non-small cell lung cancer reduces perioperative
      morbidity.
AB  - OBJECTIVE: The objective is to test the concept of "pay for performance" for
      patients with non-small cell lung cancer. METHODS: We constructed 53 benchmark
      performance standards (10 labeled "critical") and prospectively assessed the
      effect of adherence to these standards on morbidity and mortality for patients
      undergoing resection of non-small cell lung cancer. RESULTS: Between January 1,
      2007, and December 31, 2009, 778 patients with non-small cell lung cancer
      underwent thoracotomy by 1 surgeon. Ninety-seven percent of patients received all
      26 of the "day of surgery" and "intraoperative" benchmarks, and those were the
      easiest to deliver. The 469 patients who had all 53 benchmarks delivered,
      compared with the 309 who did not, had a lower mortality (2.0% vs 2.3%) and
      morbidity (16% vs 44%; P < .001). The 693 patients who received all 10 "critical"
      benchmarks, compared with the 85 who did not, had a lower mortality (1.9% vs
      4.7%) and morbidity (25% vs 41%; P = .003). Low household income and fewer than 2
      people in the household were predictors of overall morbidity on univariate
      analysis. CONCLUSIONS: Most benchmarks, especially "day of surgery" and
      "intraoperative" ones, can be delivered in more than 97% of patients. The
      delivery of benchmarks reduces perioperative morbidity but not mortality.
      Socioeconomic factors are predictors of overall morbidity. Operative mortality is
      related to the "quality of the patient" and the "quality of the health care
      provider."

PMID- 21071042
TI  - Should the proximal arch be routinely replaced in patients with bicuspid aortic
      valve disease and ascending aortic aneurysm?
AB  - OBJECTIVES: Bicuspid aortic valve is frequently associated with underlying
      aortopathy. Data support an aggressive approach to replacement of the ascending
      aorta. However, the natural history of the unreplaced aortic arch is unknown, and
      some have advocated routine replacement of the proximal arch in this setting.
      METHODS: We identified patients with bicuspid aortic valve undergoing repair or
      replacement of the ascending aorta with or without aortic valve replacement or
      root replacement between January 1988 and December 2007 at our institution.
      Follow-up was by review of clinical records and postal questionnaire. RESULTS: Of
      470 patients identified, 48 patients had hemiarch or total arch replacement and
      were excluded. Of the remaining 422 patients, 227 had separate aortic valve
      replacement or repair and ascending aortoplasty (76) or ascending aortic graft
      replacement (175), 107 a valved conduit, 40 a homograft root, and 21 a valve
      sparing root replacement. The mean age was 56 +/- 15 years, and 80% were male.
      Follow-up was up to 17 (median 4.2) years. There were 23 (5.5%) late
      reoperations, of which none were for arch dilatation. Survival at 1, 5, 10, and
      12 years was 96.5%, 89.6%, 77.7%, and 74.0%. Freedom from late reoperation was
      98.7%, 94.1%, 81.0%, and 81.0%. Paired echocardiographic measurements of aortic
      arch diameter (n = 58) were 33.3 mm preoperatively versus 31.9 mm postoperatively
      (P = .135) at a mean 4 years. CONCLUSIONS: Progressive dilatation of the aortic
      arch leading to reoperation after repair of ascending aortic aneurysm in patients
      with bicuspid aortic valve is uncommon. A selective approach to transverse aortic
      arch replacement is appropriate.

PMID- 21071043
TI  - Assessment of recent sediment influence in an urban polluted subantarctic coastal
      ecosystem. Beagle Channel (Southern Argentina).
AB  - In this study, baseline information about the environmental status of Ushuaia
      (UB) and Golondrina (GB) bays is presented. Surface and bottom seawater and
      freshwater discharged from land were evaluated. Multivariate analysis identified
      different water quality zones within the bays, two of them located next to the
      north and northwest coastlines of UB, where the majority of human activities are
      developed. Porosity, total organic matter, biochemical components, ammonium, and
      phytopigments were determined in sediment samples from each quality zone. Benthic
      fluxes of nutrients and dissolved oxygen were assessed in situ using opaque
      chambers. In northwest zone of UB, carbon equivalents of proteins and
      carbohydrates in surficial sediments were the same order as in hypertrophic
      ecosystems, whereas ammonium and phosphate released from sediment greatly
      exceeded the allochthonous sources. Management of municipal wastewater is
      required to remediate this chronic pollution.

PMID- 21071044
TI  - Differences in organotin accumulation in relation to life history in the white
      spotted charr Salvelinus leucomaenis.
AB  - To examine the accumulation pattern of organotins (OTs) in relation to the
      migration of diadromous fish, tributyltin (TBT) and triphenyltin (TPT) and their
      derivatives were determined in the muscle tissue of both sea-run (anadromous) and
      freshwater-resident (nonanadromous) types of the white-spotted charr Salvelinus
      leucomaenis. Ontogenic changes in otolith strontium (Sr) and calcium (Ca)
      concentrations were examined along life history transect to discriminate
      migration type. Mean Sr:Ca ratio from the core to the edge of the otolith in sea
      run individuals was significantly higher than those in freshwater-resident one.
      There were no significant correlations in S. leucomaenis between OT accumulation
      and various biological characteristics. It is noteworthy that TBT and TPT
      concentrations in sea-run type were significantly higher than those in freshwater
      resident individuals, although they are both of the same species. These results
      suggest that sea-run S. leucomaenis have a higher ecological risk of OT exposure
      than freshwater-residents during their life histories.

PMID- 21071045
TI  - Effects of extreme climate events on the macrobenthic communities' structure and
      functioning of a temperate estuary.
AB  - The Mondego estuary (Portugal) experienced profound structural and functional
      modifications due to eutrophication, which was exacerbated by consecutive weather
      extremes that compromised a previous restoration project. This work explores
      multiple climate impacts on macrobenthic communities' structure and functioning
      and its implications on ecosystem's recovery. Floods and heat waves had a
      stronger negative effect on macrobenthic assemblages than the droughts, imposing
      a total abundance decline. Contrarily, biomass was not so affected by climate
      events, being stable and even increased in a mudflat area, where seagrass is re
      colonizing. Bivalves and oligochaetes decreased with the flooding episodes,
      likewise subsurface-deposit feeders and suspension feeders, while crustaceans
      were particularly sensitive to heat waves. Species richness declined with the
      floods and heat waves, whilst evenness increased in sandflat area, constituting a
      positive sign towards recovery. Succession of different climate extremes affected
      ecosystem structure and functioning, delaying its recovery with possible
      consequent effects at higher trophic levels.

PMID- 21071046
TI  - Ferredoxin:NADP+ oxidoreductase as a target of Cd2+ inhibitory action-
      biochemical studies.
AB  - The ferredoxin:NADP+ oxidoreductase (FNR) catalyses the ferredoxin-dependent
      reduction of NADP+ to NADPH in linear photosynthetic electron transport. The
      enzyme also transfers electrons from reduced ferredoxin (Fd) or NADPH to the
      cytochrome b(6)f complex in cyclic electron transport. In vitro, the enzyme
      catalyses the NADPH-dependent reduction of various substrates, including
      ferredoxin, the analogue of its redox centre - ferricyanide, and the analogue of
      quinones, which is dibromothymoquinone. This paper presents results on the
      cadmium-induced inhibition of FNR. The K(i) value calculated for research
      condition was 1.72 mM. FNR molecule can bind a large number of cadmium ions, as
      shown by the application of cadmium-selective electrode, but just one ion remains
      bound after dialysis. The effect of cadmium binding is significant disturbance in
      the electron transfer process from flavin adenine dinucleotide (FAD) to
      dibromothymoqinone, but less interference with the reduction of ferricyanide.
      However, it caused a strong inhibition of Fd reduction, indicating that Cd
      induced changes in the FNR structure disrupt Fd binding. Additionally, the
      protonation of the thiol groups is shown to be of great importance in the
      inhibition process. A mechanism for cadmium-caused inhibition is proposed and
      discussed with respect to the in vitro and in vivo situation.

PMID- 21071047
TI  - 2-Aminoethoxydiphenyl borate (2-APB) reduces respiratory burst, MMP-9 release and
      CD11b expression, and increases l-selectin shedding in bovine neutrophils.
AB  - This study describes the effect of 2-aminoethoxydiphenyl borate (2-APB), a
      putative store-operated calcium (Ca(2+)) entry (SOCE) inhibitor, on reactive
      oxygen species (ROS) production, matrix metalloproteinase 9 (MMP-9) release,
      CD11b and l-selectin (CD62L) expression, size changes and apoptosis in bovine
      neutrophils stimulated with platelet-activating factor (PAF). It was observed
      that doses ?1MUM 2-APB significantly reduced ROS production, whereas 50 and
      100MUM 2-APB reduced MMP-9 release induced by PAF. Moreover, concentrations
      ?10MUM 2-APB reduced CD11b expression and increased l-selectin shedding. PAF
      induced size changes in neutrophils, and this effect was inhibited by 2-APB. From
      this work it is possible to conclude that 2-APB at concentrations that inhibit
      SOCE responses was able to inhibit ROS and MMP-9 release and CD11b expression,
      and increase l-selectin shedding, suggesting that the Ca(2+) channel involved in
      SOCE is a potential target for the development of new anti-inflammatory drugs in
      cattle.

PMID- 21071048
TI  - Transcriptional profiling of antimicrobial peptides avian beta-defensins in the
      chicken ovary during sexual maturation and in response to Salmonella enteritidis
      infection.
AB  - Avian beta-defensins (AvbetaDs) are antimicrobial peptides that play significant
      roles in the innate immune system in chickens. The aim of this study was to
      identify the types of AvbetaDs expressed in the chicken ovary, to investigate the
      effects of sexual maturation in the ovarian mRNA abundance and to determine the
      changes in their expression levels as a result to Salmonella enteritidis (SE)
      infection. RNA was extracted from the ovary of healthy prepubertal, sexually
      mature and aged birds, as well as from sexually mature and aged SE infected
      birds. Real-time PCR analysis revealed that 11 AvbetaDs genes were expressed in
      the chicken ovary. A significant up regulation of AvbetaD1, 3, 4, 5, 7 and 11 was
      observed in the ovary of sexually mature and aged birds. Furthermore, a
      significant up-regulation of AvbetaD4, 5, 7, 11 and 12 was observed in the ovary
      of SE infected sexually mature birds. These results suggest that the mRNA
      expression of at least six AvbetaDs increase with age in the ovary of laying
      hens, and that at least five AvbetaDs show an induction in their expression in
      response to SE infection, indicating an AvbetaD-mediated immune response
      mechanism in the chicken ovary.

PMID- 21071049
TI  - Computed tomography measurements of thoracic structures in 26 clinically normal
      goats.
AB  - The present study was performed to provide computed tomographic (CT) reference
      values for structures in the thorax of 26 clinically normal Saanen goats. Animals
      were anesthetized, positioned in sternal recumbency and transverse images with a
      reconstructed 1.5mm slice thickness were obtained by use of a 40-slice CT
      scanner. Absolute and relative measurements of the trachea, heart, cranial vena
      cava, thoracic aorta, caudal vena cava, right and left principal bronchus, right
      and left caudal lobar bronchus and the concomitant branch of the right and left
      pulmonary artery and vein, large caudal mediastinal lymph node and lung density
      were performed with dedicated software. Minimal to moderate interstitial or
      bronchopneumonia was incidentally found on CT in 24 animals. In conclusion, CT
      images obtained in this study can be used as a reference for the evaluation of
      thoracic diseases in goats.

PMID- 21071050
TI  - [Retinal involvement and genetic myopathy].
AB  - INTRODUCTION: In genetic diseases, association between retinal and muscular
      involvement is uncommon, quite specific and frequently allows the diagnosis. In
      this context, three types of retinal involvement have been described: retinitis
      pigmentosa (RP), pattern retinal dystrophy (PRD) and exudative retinitis
      resembling Coats disease (CD). STATE OF THE ART: The association between RP, PRD
      and muscle weakness is highly evocative of a mitochondrial disorder. Extra ocular
      muscles may be affected, but limb girdle or distal weakness can also be present
      in association or not with symptoms and signs of multisystemic involvement. In a
      large number of patients suffering from facioscapulohumeral muscular dystrophy
      (FSHD), retinal vessels telangectasia can be found at the fundoscopic
      examination. This finding, which corresponds to a developmental abnormality of
      peripheral retinal blood vessels, is not progressive and remains clinically
      asymptomatic. Nevertheless, a few patients with FSHD can develop an exsudative
      retinopathy resembling Coats disease with the risk of the major complication,
      recurrent retinal detachments. PERSPECTIVES AND CONCLUSIONS: Considering the
      diagnostic interest and the deleterious consequences that may follow retinal
      involvement, close collaboration between the neurologist and ophthalmologist is
      needed in order to establish the diagnosis, detect complications early, and set
      up appropriate therapies.

PMID- 21071051
TI  - Microsporidial keratitis: need for increased awareness.
AB  - Since the devastation of the European silk worm industry in the 19th century,
      microsporidia have been recognized as important organisms. An enormous literature
      is available on their biology, phylogeny, classification, disease profile,
      diagnosis, and treatment; however, it is only recently that ophthalmologists have
      begun to take note of these organisms. The last two decades have seen several
      publications related to ocular microsporidiosis, in particular those forms
      affecting the cornea. Both immunocompetent and immunocompromised patients are at
      risk of developing corneal infections that may range from self limiting mild
      keratoconjunctivitis to severe stromal keratitis recalcitrant to medical
      treatment. Exposure to soil, muddy water, and minor trauma are possible risk
      factors. Although reliable prevalence data are lacking, recent studies indicate a
      high prevalence of microsporidial keratoconjunctivitis in the rainy season,
      especially in India and other countries with similar climates. For instance, a
      high prevalence has been documented in Singapore. We bring together the
      information available on ocular microsporidiosis.

PMID- 21071052
TI  - RNA chaperone activity of the tombusviral p33 replication protein facilitates
      initiation of RNA synthesis by the viral RdRp in vitro.
AB  - Small plus-stranded RNA viruses do not code for RNA helicases that would
      facilitate the proper folding of viral RNAs during replication. Instead, these
      viruses might use RNA chaperones as shown here for the essential p33 replication
      protein of Tomato bushy stunt virus (TBSV). In vitro experiments demonstrate that
      the purified recombinant p33 promotes strand separation of a DNA/RNA duplex. In
      addition, p33 renders dsRNA templates sensitive to single-strand specific S1
      nuclease, suggesting that p33 can destabilize highly structured RNAs. We also
      demonstrate that the RNA chaperone activity of p33 facilitates self-cleavage by a
      ribozyme in vitro. In addition, purified p33 facilitates in vitro RNA synthesis
      on double-stranded (ds)RNA templates up to 5-fold by a viral RNA-dependent RNA
      polymerase. We propose that the RNA chaperone activity of p33 facilitates the
      initiation of plus-strand synthesis as well as affects RNA recombination.
      Altogether, the TBSV RNA chaperone might perform similar biological functions to
      the helicases of other RNA viruses with much larger coding capacity.

PMID- 21071053
TI  - The host outer membrane proteins OmpA and OmpC are associated with the Shigella
      phage Sf6 virion.
AB  - Assembly of dsDNA bacteriophage is a precisely programmed process. Potential
      roles of host cell components in phage assembly haven't been well understood. It
      was previously reported that two unidentified proteins were present in
      bacteriophage Sf6 virion (Casjens et al, 2004, J.Mol.Biol. 339, 379-394, Fig.
      2A). Using tandem mass spectrometry, we have identified the two proteins as outer
      membrane proteins (OMPs) OmpA and OmpC from its host Shigella flexneri. The
      transmission electron cryo-microscopy structure of Sf6 shows significant density
      at specific sites at the phage capsid inner surface. This density fit well with
      the characteristic beta-barrel domains of OMPs, thus may be due to the two host
      proteins. Locations of this density suggest a role in Sf6 morphogenesis
      reminiscent of phage-encoded cementing proteins. These data indicate a new, OMP
      related phage:host linkage, adding to previous knowledge that some lambdoid
      bacteriophage genomes contain OmpC-like genes that express phage-encoded porins
      in the lysogenic state.

PMID- 21071054
TI  - Mutational pathways and genetic barriers to CXCR4-mediated entry by human
      immunodeficiency virus type 1.
AB  - To examine mutational pathways that lead to CXCR4 use of HIV-1, we analyzed the
      genotypic and phenotypic characteristics of envelope sequences from a large panel
      of patient virus populations and individual clones containing different V3
      mutations. Basic amino acid substitutions at position 11 were strong determinants
      of CXCR4-mediated entry but required multiple compensatory mutations to overcome
      associated reductions in infectivity. In contrast, basic amino acid substitutions
      at position 25, or substitutions at positions 6-8 resulting in the loss of a
      potential N-linked glycosylation site, contributed to CXCR4-mediated entry but
      required additional substitutions acting cooperatively to confer efficient CXCR4
      use. Our assumptions, based upon examination of patient viruses, were largely
      confirmed by characterizing the coreceptor utilization of five distinct panels of
      isogenic envelope sequences containing V3 amino acid substitutions introduced by
      site-directed mutagenesis. These results further define the mutational pathways
      leading to CXCR4 use and their associated genetic barriers.

PMID- 21071056
TI  - Exploring 17alpha-ethinylestradiol removal, mineralization, and bioincorporation
      in engineered bioreactors.
AB  - This research investigated removal, mineralization, and bioincorporation of
      17alpha-ethinylestradiol (EE(2)) in membrane bioreactors and conventional
      bioreactors. When the influent EE(2) concentration was >50 MUg/L, the membrane
      bioreactor (MBR) biomass removed more EE(2) than conventional bioreactor (CBR)
      biomass in continuous tests, likely because the sorption partitioning
      coefficients are higher for MBR biomass. Microautoradiography was carried out to
      investigate the distribution of EE(2) within the aggregates retrieved from the
      bioreactors, and the results revealed concentration gradients present within the
      floc. Experiments using radiolabeled (14)C-EE(2) experiments (done with 24.5
      MUg/L EE(2)) showed that EE(2) removal rates and the amount of EE(2) mineralized
      were similar in MBRs and CBRs. Direct measurements and bioenergetic estimates
      suggest that EE(2)-related carbon is probably incorporated into active biomass,
      despite the fact that EE(2) was added at a concentration that was much lower than
      that of the primary growth substrates.

PMID- 21071055
TI  - Poxvirus interleukin-4 expression overcomes inherent resistance and vaccine
      induced immunity: pathogenesis, prophylaxis, and antiviral therapy.
AB  - In 2001, Jackson et al. reported that murine IL-4 expression by a recombinant
      ectromelia virus caused enhanced morbidity and lethality in resistant C57BL/6
      mice as well as overcame protective immune memory responses. To achieve a more
      thorough understanding of this phenomenon and to assess a variety of
      countermeasures, we constructed a series of ECTV recombinants encoding murine IL
      4 under the control of promoters of different strengths and temporal regulation.
      We showed that the ECTV-IL-4 recombinant expressing the highest level of IL-4 was
      uniformly lethal for C57BL/6 mice even when previously immunized. The lethality
      of the ECTV-IL-4 recombinants resulted from virus-expressed IL-4 signaling
      through the IL-4 receptor but was not due to IL-4 toxicity. A number of treatment
      approaches were evaluated against the most virulent IL-4 encoding virus. The most
      efficacious therapy was a combination of two antiviral drugs (CMX001((r)) and ST
      246((r))) that have different mechanisms of action.

PMID- 21071057
TI  - Temporal and geographical genetic variation in the amphipod Melita plumulosa
      (Crustacea: Melitidae): Link of a localized change in haplotype frequencies to a
      chemical spill.
AB  - Anthropogenic effects such as contamination affect the genetic structure of
      populations. This study examined the temporal and geographical patterns of
      genetic diversity among populations of the benthic crustacean amphipod Melita
      plumulosa in the Parramatta River (Sydney, Australia), following an industrial
      chemical spill. The spill of an acrylate/methacrylate co-polymer in naphtha
      solvent occurred in July 2006. M. plumulosa were sampled temporally between
      December 2006 and November 2009 and spatially in November 2009. Genetic variation
      was examined at the mitochondrial cytochrome c oxidase subunit I locus. Notably,
      nucleotide diversity was low and Tajima's D was significantly negative amongst
      amphipods collected immediately downstream from the spill for 10 months. We
      hypothesize that the spill had a significant localized effect on the genetic
      diversity of M. plumulosa. Alternate explanations include an alternate and
      unknown toxicant or a localized sampling bias. Future proposed studies will
      dissect these alternatives.

PMID- 21071058
TI  - Temperature-dependent sorption of polycyclic aromatic hydrocarbons on natural and
      treated sediments.
AB  - In aqueous environment temperature is considered to play a significant role in
      the sorption process of polycyclic aromatic hydrocarbons (PAHs) and its influence
      on the sorption equilibrium is indicative of sorption energies and mechanisms. In
      this study, sorptions of five PAHs on three heterogeneous sorbents including one
      river sediment (YHR), one estuary sediment (YRD) and one treated sediment with
      organic matter removed (IM) were carried out at a range of temperature from 5 
      degrees C to 35  degrees C. Stronger sorptions were observed at lower
      temperatures, with the equilibrium sorption coefficient Kd increasing 2-5 times
      as the temperature decreases 30  degrees C. The increase of Kd value was
      attributed primarily to the change of PAH water solubility, which predicted 40
      75% of the increase of Kd in the sorption process. To provide insight into the
      sorption mechanism, enthalpy change (DeltaHS) for the sorption process was
      calculated and the values were observed to be negative for all of the
      interactions, suggesting that the exothermal sorption of PAHs inversely
      dependents on temperature. Based on the values of DeltaHS, van der Waals forces
      were inferred as the main sorption mechanism for the PAHs, especially on the YHR
      sediment which contained more organic matter. For sorption of larger size PAHs on
      the sorbents with low organic matter, specific interactions were deduced to
      contribute to the overall sorption.

PMID- 21071059
TI  - Spinal deformities in the black-striped pipefish Syngnathus abaster (Pisces,
      Syngnathidae) from the Tunis North Lake, Tunisia.
AB  - Spinal deformities are seen in fishes. Deformities in the family Syngnathidae is
      rarely reported. Spine curvatures in natural population of pipefish, Syngnathus
      abaster are reported from the Tunis North Lake. The species is euryhaline and
      occurs along the Mediterranean coasts. Four hundred specimens of S. abaster were
      collected from January 2006 to December 2007 from the Tunis North Lake. Two
      specimens with skeletal abnormalities were described for the first time. X-rays
      radiographies revealed several vertebral deformities for each deformed specimen,
      especially at five curvation places of the caudal part. Several factors are
      believed to be the cause of spinal deformities of S. abaster in the Tunis North
      Lake, such as environmental disturbances, parasitism infection and nutritional
      factors.

PMID- 21071060
TI  - Resolving the variability of CDOM fluorescence to differentiate the sources and
      fate of DOM in Lake Taihu and its tributaries.
AB  - Taihu Basin is the most developed area in China, which economic development has
      resulted in pollutants being produced and discharged into rivers and the lake.
      Lake Taihu is located in the center of the basin, which is characterized by a
      complex network of rivers and channels. To assess the sources and fate of
      dissolved organic matter (DOM) in surface waters, we determined the components
      and abundance of chromophoric dissolved organic matter (CDOM) within Lake Taihu
      and 66 of its tributaries, and 22 sites along transects from two main rivers. In
      Lake Taihu, there was a relative less spatial variation in CDOM absorption
      a(CDOM)(355) with a mean of 2.46 +/- 0.69 m-1 compared to the mean of 3.36 +/-
      1.77 m-1 in the rivers. Two autochthonous tryptophan-like components (C1 and C5),
      two humic-like components (C2 and C3), and one autochthonous tyrosine-like
      component (C4) were identified using the parallel factor analysis (PARAFAC)
      model. The C2 and C3 had a direct relationship with a(CDOM)(355), dissolved
      organic carbon (DOC), and chemical oxygen demand (COD). The separation of lake
      samples from river samples, on both axes of the Principal Component Analysis
      (PCA), showed the difference in DOM fluorophores between these various
      environments. Components C1 and C5 concurrently showed positive factor 1
      loadings, while C4 was close to the negative factor 1 axis. Components C2 and C3
      showed positive second factor loadings. The major contribution of autochthonous
      tryptophan-like components to lake samples is due to the autochthonous production
      of CDOM in the lake ecosystems. The results also showed that the differences in
      geology and associated land use control CDOM dynamics, such as the high levels of
      CDOM with terrestrial characteristics in the northwestern upstream rivers and low
      levels of CDOM with increased microbial characteristics in the southwestern
      upstream rivers. Most of river samples from the downstream regions in the eastern
      and southeastern plains had a similar relative abundance of humic-like
      fluorescence, with less of the tryptophan-like and more of the tyrosine-like
      contributions than did samples from upstream regions.

PMID- 21071061
TI  - Uptake of carbamazepine by cucumber plants--a case study related to irrigation
      with reclaimed wastewater.
AB  - Reclaimed wastewater is an important source of irrigation in semiarid and arid
      zones. Here we report data on carbamazepine (CBZ) uptake by cucumber plants in
      hydroponic culture and greenhouse experiments using different soil types
      irrigated with fresh water or reclaimed wastewater. Data obtained from the
      hydroponic culture experiments suggest that CBZ is mainly translocated by water
      mass flow, and thus it is concentrated and accumulated to the largest extent in
      the mature/older leaves. Carbamazepine concentration in cucumber fruits and
      leaves was negatively correlated with soil organic matter content. The
      concentrations of CBZ in the roots and stems were relatively low, and most CBZ in
      the plant (76-84% of total uptake) was detected in the leaves. A greenhouse
      experiment using fresh water and reclaimed wastewater spiked, or not, with CBZ at
      1 MUg L(-1) (typical concentration in effluents) revealed that CBZ can be taken
      up and bioaccumulated from its background concentration in reclaimed wastewater.
      Bioaccumulation factor (calculated as the ratio of CBZ concentration in the plant
      to that in the soil solution) for the fruits (0.8-1) was significantly lower than
      the value calculated for the leaves (17-20). This study emphasizes the potential
      uptake of active pharmaceutical compounds by crops in organic-matter-poor soils
      irrigated with reclaimed wastewater and highlights the potential risks associated
      with this agricultural practice.

PMID- 21071062
TI  - Hydroxylated polychlorobornanes--synthesis and characterization of new potential
      toxaphene metabolites.
AB  - For decades, toxaphene had been used as a major chloropesticide. Degradation of
      the multicomponent mixture in the environment was mainly reported to be due to
      anaerobic dechlorination and hydrodechlorination. Little was known about
      oxidative transformation processes and the potential hydroxylated metabolites
      were not available as standard compounds. For this reason we synthesized
      hydroxylated polychlorobornanes by the UV-induced photochlorination of 2-endo
      bornyl acetate with sulfuryl chloride followed by hydrolysis of the acetate
      moiety. The released polychlorinated 2-endo-hydroxybornanes were slightly higher
      chlorinated the longer the reaction was maintained. After 8h, the main products
      were pentachlorinated hydroxybornanes followed by hexa- and heptachlorinated
      homologues. Traces of octachlorinated hydroxybornanes were also observed. The
      GC/ECNI-MS spectra of the products were characterized by the molecular ions and
      the [M-Cl]- fragment ions. The molecular ions of the polychlorinated
      hydroxybornanes are isobaric with those of polychlorinated biphenyls. E.g.
      hexachlorohydroxybornanes (C10H12Cl6O) and hexachlorobiphenyls (C12H4Cl6) show
      the molecular ion at m/z 358. Based on fractionation experiments on silica with
      the synthesis products it might be possible that OH-CTTs if present in samples
      will elute into a more polar fraction usually discarded or not collected. Both
      problems might explain why these compounds have not been more frequently
      described in the scientific literature.

PMID- 21071063
TI  - Removal of carbon nanotubes from aqueous environment with filter paper.
AB  - The potential health and environmental hazards of carbon nanotubes (CNTs) have
      been a concerned issue. However, in contrast to the wide recognition of the
      toxicity of CNTs, little attention has been paid to the
      decontamination/remediation of CNT pollution. In this study, we report that CNTs
      can be removed from aqueous environment. In the presence of Ca2(+), CNTs
      aggregate quickly to micron size and then enable easy and effective removal via
      normal filtration. After filtration, CNT suspension becomes colorless with the
      remnant CNT concentration less than 0.5 MUg mL-1, a safe dose based on the
      published data. The filtration approach also works well in the presence of
      typical surfactant and dissolved organic matter. The removal efficiency is Ca2(+)
      concentration-dependent and regulated by the initial pH value and ionic strength.
      Our study is helpful for future decontamination of CNTs from aqueous environment.

PMID- 21071064
TI  - Mortality and the magnitude of the "wild effect" in chimpanzee tooth emergence.
AB  - Age of tooth emergence is a useful measure of the pace of life for primate
      species, both living and extinct. A recent study combining wild chimpanzees of
      the Tai Forest, Gombe, and Bossou by Zihlman et al. (2004) suggested that wild
      chimpanzees erupt teeth much later than captives, bringing into question both
      comparisons within the hominin fossil record and assessment of chimpanzees. Here,
      we assess the magnitude of the "wild effect" (the mean difference between captive
      and wild samples expressed in standard deviation units) in these chimpanzees.
      Tooth emergence in these wild individuals is late, although at a more moderate
      level than previously recorded, with a mean delay conservatively estimated at
      about 1 SD compared to the captive distributions. The effect rises to 1.3 SD if
      we relax criteria for age estimates. We estimate that the mandibular M1 of these
      wild chimpanzees emerges at about 3 (2)/(3)-3 3/4 years of age. An important
      point, often ignored, is that these chimpanzees are largely dead of natural
      causes, merging the effect of living wild with the effect of early death.
      Evidence of mortality selection includes, specifically: younger deaths appear to
      have been more delayed than the older in tooth emergence, more often showed
      evidence of disease or debilitation, and revealed a higher occurrence of dental
      anomalies. Notably, delay in tooth emergence for live-captured wild baboons
      appears lower in magnitude (ca. 0.5 SD) and differs in pattern. Definitive ages
      of tooth emergence times in living wild chimpanzees must be established from the
      study of living animals. The fossil record, of course, consists of many dead
      juveniles; the present study has implications for how we evaluate them.

PMID- 21071065
TI  - Soil erosion and sediment yield and their relationships with vegetation cover in
      upper stream of the Yellow River.
AB  - Soil erosion is a significant concern when considering regional environmental
      protection, especially in the Yellow River Basin in China. This study evaluated
      the temporal-spatial interaction of land cover status with soil erosion
      characteristics in the Longliu Catchment of China, using the Soil and Water
      Assessment Tool (SWAT) model. SWAT is a physical hydrological model which uses
      the RUSLE equation as a sediment algorithm. Considering the spatial and temporal
      scale of the relationship between soil erosion and sediment yield, simulations
      were undertaken at monthly and annual temporal scales and basin and sub-basin
      spatial scales. The corresponding temporal and spatial Normalized Difference
      Vegetation Index (NDVI) information was summarized from MODIS data, which can
      integrate regional land cover and climatic features. The SWAT simulation revealed
      that the annual soil erosion and sediment yield showed similar spatial
      distribution patterns, but the monthly variation fluctuated significantly. The
      monthly basin soil erosion varied from almost no erosion load to 3.92 t/ha and
      the maximum monthly sediment yield was 47,540 tones. The inter-annual simulation
      focused on the spatial difference and relationship with the corresponding
      vegetation NDVI value for every sub-basin. It is concluded that, for this
      continental monsoon climate basin, the higher NDVI vegetation zones prevented
      sediment transport, but at the same time they also contributed considerable soil
      erosion. The monthly basin soil erosion and sediment yield both correlated with
      NDVI, and the determination coefficients of their exponential correlation model
      were 0.446 and 0.426, respectively. The relationships between soil erosion and
      sediment yield with vegetation NDVI indicated that the vegetation status has a
      significant impact on sediment formation and transport. The findings can be used
      to develop soil erosion conservation programs for the study area.

PMID- 21071066
TI  - Concentrations of ultrafine particles at a highway toll collection booth and
      exposure implications for toll collectors.
AB  - Research regarding the magnitude of ultrafine particle levels at highway toll
      stations is limited. This study measured ambient concentrations of ultrafine
      particles at a highway toll station from October 30 to November 1 and November 5
      to November 6, 2008. A scanning mobility particle sizer was used to measure
      ultrafine particle concentrations at a ticket/cash tollbooth. Levels of hourly
      average ultrafine particles at the tollbooth were about 3-6 times higher than
      those in urban backgrounds, indicating that a considerable amount of ultrafine
      particles are exhausted from passing vehicles. A bi-modal size distribution
      pattern with a dominant mode at about <6 nm and a minor mode at about 40 nm was
      observed at the tollbooth. The high amounts of nanoparticles in this study can be
      attributed to gas-to-particle reactions in fresh fumes emitted directly from
      vehicles. The influences of traffic volume, wind speed, and relative humidity on
      ultrafine particle concentrations were also determined. High ambient
      concentrations of ultrafine particles existed under low wind speed, low relative
      humidity, and high traffic volume. Although different factors account for high
      ambient concentrations of ultrafine particles at the tollbooth, measurements
      indicate that toll collectors who work close to traffic emission sources have a
      high exposure risk.

PMID- 21071067
TI  - Ambient wood smoke exposure and respiratory symptoms in Tasmania, Australia.
AB  - Wood smoke exposure has been associated with adverse respiratory health outcomes,
      with much of the current research focused on wood smoke from domestic heating and
      cooking. This study examined the association between respiratory symptoms and
      outdoor wood smoke in Launceston, Tasmania, where ~30% of homes use wood burners
      for domestic heating. This ecological study examined data from participants of
      the 2004 Tasmanian Longitudinal Health Study postal survey and compared the
      prevalence of respiratory symptoms in Launceston (n=601) with that in Hobart
      (n=1071), a larger Tasmanian city with much less wood smoke. Multivariate
      logistic regression models were used to investigate the associations of interest
      while adjusting for gender, atopy, history of allergic disease and current
      smoking status. There were no significant differences in symptom prevalence
      between Launceston and Hobart. Two subgroup analyses, which examined participants
      with pre-existing chronic respiratory disease, and those who reported actively
      using a wood burner in their home, also did not find significant differences. Any
      impact of wood smoke on non-specific respiratory symptoms might have been
      overshadowed by other important determinants of respiratory health, such as
      vehicle exhaust and tobacco smoking, or were too small to have been detected.
      However, the lack of detectable differences in symptom prevalence might also
      reflect the success of regulatory action by local governments to reduce wood
      smoke emissions in Launceston. The results of other epidemiological studies
      support an association between ambient wood smoke exposure and adverse
      respiratory health. Further investigations of wood smoke exposure in Australian
      settings are needed to investigate the lack of significant associations found in
      this study, especially studies of indoor air quality and health impacts in
      children and elderly populations.

PMID- 21071068
TI  - Cancer in the Sudan: an overview of the current status of knowledge on tumor
      patterns and risk factors.
AB  - The Sudan, the largest and most diverse country in Africa, is experiencing a
      growing cancer problem, but little is presently known on tumor patterns, cancer
      epidemiology and ethnic or environmental cancer risk factors. We review here the
      current status of knowledge, summarizing data from local and international
      publications as well as primary information from the only two cancer hospitals of
      the country, both located in Central Sudan (Khartoum and Wad Medani). We provide
      frequencies reported for cancers detected in adults and children, and summarize
      studies on specific cancer types, as well as information on risk factors that
      most likely impact on tumor patterns.

PMID- 21071069
TI  - Pathogen sensing, subsequent signalling, and signalosome in human platelets.
AB  - Beyond haemostasis, platelets exert a potent role in innate immunity and
      particularly in its inflammatory arm. The extent of this action remains however
      debatable, despite clear - and old - evidence of a link between platelets and
      infection. Platelets can sense infectious pathogens by pathogen recognition
      receptors and they can even discriminate between various types of infectious
      signatures. In reply, they can shape their capacity to respond by activating a
      signalosome and by producing different profiles of pro-inflammatory cytokines and
      related products. The links between pathogen sensing, signalosome activation and
      protein production, and their finely tuned regulation are still under
      investigation since platelets lack a nucleus and thus, canonical molecular
      biology and genomics apparati.

PMID- 21071070
TI  - Impact of prostate weight on probability of positive surgical margins in patients
      with low-risk prostate cancer after robotic-assisted laparoscopic radical
      prostatectomy.
AB  - OBJECTIVE: To evaluate the impact of prostate weight (PW) on probability of
      positive surgical margin (PSM) in patients undergoing robotic-assisted radical
      prostatectomy (RARP) for low-risk prostate cancer. METHODS: The cohort consisted
      of 690 men with low-risk prostate cancer (clinical stage T1c, prostate-specific
      antigen <10 ng/mL, biopsy Gleason score <=6) who underwent RARP with bilateral
      nerve-sparing at our institution by 1 of 2 surgeons from 2003 to 2009. PW was
      obtained from the pathologic specimen. The association between probability of PSM
      and PW was assessed with univariate and multivariate logistic regression
      analysis. RESULTS: A PSM was identified in 105 patients (15.2%). Patients with
      PSM had significant higher prostate-specific antigen (P = .04), smaller prostates
      (P = .0001), higher Gleason score (P = .004), and higher pathologic stage (P <
      .0001). After logistic regression, we found a significant inverse relation
      between PSM and PW (OR 0.97%; 95% confidence interval [CI] 0.96, 0.99; P = .0003)
      in univariate analysis. This remained significant in the multivariate model (OR
      0.98%; 95% CI 0.96, 0.99; P = .006) adjusting for age, body mass index, surgeon
      experience, pathologic Gleason score, and pathologic stage. In this multivariate
      model, the predicted probability of PSM for 25-, 50-, 100-, and 150-g prostates
      were 22% (95% CI 16%, 30%), 13% (95% CI 11%, 16%), 5% (95% CI 1%, 8%), and 1%
      (95% CI 0%, 3%), respectively. CONCLUSIONS: Lower PW is independently associated
      with higher probability of PSM in low-risk patients undergoing RARP with
      bilateral nerve-sparing.

PMID- 21071071
TI  - Inhibitory effects of T/L-type calcium channel blockers on tubulointerstitial
      fibrosis in obstructed kidneys in rats.
AB  - OBJECTIVES: To examine the effect of L- and T/L-type calcium channel blockers on
      interstitial fibrosis in chronic unilateral ureteral obstruction (UUO).
      Tubulointerstitial fibrosis is a common outcome of several progressive renal
      diseases. Calcium channel blockers are widely used for the treatment of
      hypertension with renal diseases; however, the direct effect of calcium channel
      blockers on renal diseases independent of lowering blood pressure has not been
      fully elucidated. METHODS: Sprague-Dawley rats were divided into 3 treatment
      groups: (1) vehicle control; (2) nifedipine, an L-type calcium channel blockers;
      and (3) efonidipine, a T/L-type calcium channel blockers. Treatment was initiated
      1 day before and continued until 6 days after creation of the UUO. RESULTS:
      Tubulointerstitial fibrosis in the obstructed kidney was significantly increased
      compared with that in the contralateral unobstructed kidney. Furthermore, the
      increased fibrosis was accompanied by increased fibrogenic signaling expressed by
      transforming growth factor beta1 and connective tissue growth factor mRNA levels,
      increased oxidative stress expressed by p22phox, p47phox and gp91phox mRNA level.
      Moreover, treatment with a nonhypotensive dose of efonidipine but not nifedipine
      in the obstructed kidney significantly suppressed the fibrogenic signaling and
      the oxidative stress, resulting in reduced tubulointerstitial fibrosis. The
      plasma aldosterone level in efonidipine-treated animals was increased compared
      with vehicle-treated animals, although not significantly. The increased plasma
      aldosterone level did not increase sgk-1 mRNA level in efonidipine but not in
      nifedipine treated animals. CONCLUSIONS: Treatment with efonidipine improved
      tubulointerstitial fibrosis more effectively than treatment with nifedipine in
      UUO. The antifibrogenic effect by efonidipine was obtained through suppression of
      fibrogenic signaling.

PMID- 21071072
TI  - Influence of surface conditioning and cleaning methods on resin bonding to
      zirconia ceramic.
AB  - OBJECTIVES: The purpose of this laboratory study was to evaluate the influence of
      different surface conditioning, new ceramic primers and cleaning methods on the
      bond strength of luting resin to zirconia ceramic (e.max ZirCAD). METHODS: A
      total of 96 zirconia ceramic discs were divided into six groups (n=16) according
      to surface conditioning, cleaning methods and ceramic primers. Zirconia ceramic
      discs were either air-abraded with 110 MUm alumina particles or tribochemically
      silica-coated (Rocatec). Visible dust resulting from air-borne particle abrasion
      or silica coating was removed either by oil-free air stream or by ultrasonic
      cleaning in alcohol. Then either a conventional silane (Espe Sil) or a universal
      primer containing a silane and a phosphate monomer (Monobond Plus) were applied
      to the conditioned surface. Transparent plastic tubes filled with composite resin
      were bonded to the zirconia ceramic discs using a luting resin (MultiLink
      Automix). The bonded specimens were stored in water at 37 degrees C for 3 days
      and for 30 days with 7500 thermal cycles between 5 degrees C and 55 degrees C
      prior to tensile test. Statistical analyses were conducted with three-, two- and
      one-way ANOVAs followed by comparison of means with Tukey's HSD test. RESULTS:
      Tensile bond strength ranged from 31.5 to 45.2 MPa after 3 days and from 10.6 to
      38.8 MPa after 30 days storage in water with thermal cycling. After artificial
      aging the decrease in bond strength was significant when the conventional silane
      was applied after silica coating or when the universal primer was used after air
      borne particle abrasion without ultrasonic cleaning (P<.05). However after
      artificial aging, the decrease in bond strength was not significant (P>.05) when
      the universal primer was used after air-borne particle abrasion with ultrasonic
      cleaning or after silica coating. SIGNIFICANCE: A new universal primer improved
      bonding to zirconia ceramic while the cleaning method had little or no effect.

PMID- 21071073
TI  - Mobile phones to improve HIV treatment adherence.

PMID- 21071074
TI  - Effects of a mobile phone short message service on antiretroviral treatment
      adherence in Kenya (WelTel Kenya1): a randomised trial.
AB  - BACKGROUND: Mobile (cell) phone communication has been suggested as a method to
      improve delivery of health services. However, data on the effects of mobile
      health technology on patient outcomes in resource-limited settings are limited.
      We aimed to assess whether mobile phone communication between health-care workers
      and patients starting antiretroviral therapy in Kenya improved drug adherence and
      suppression of plasma HIV-1 RNA load. METHODS: WelTel Kenya1 was a multisite
      randomised clinical trial of HIV-infected adults initiating antiretroviral
      therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple
      randomisation with a random number generating program to a mobile phone short
      message service (SMS) intervention or standard care. Patients in the intervention
      group received weekly SMS messages from a clinic nurse and were required to
      respond within 48 h. Randomisation, laboratory assays, and analyses were done by
      investigators masked to treatment allocation; however, study participants and
      clinic staff were not masked to treatment. Primary outcomes were self-reported
      ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12
      month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies
      per mL) at 12 months. The primary analysis was by intention to treat. This trial
      is registered with ClinicalTrials.gov, NCT00830622. FINDINGS: Between May, 2007,
      and October, 2008, we randomly assigned 538 participants to the SMS intervention
      (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273
      patients receiving the SMS intervention compared with 132 of 265 in the control
      group (relative risk [RR] for non-adherence 0.81, 95% CI 0.69-0.94; p=0.006).
      Suppressed viral loads were reported in 156 of 273 patients in the SMS group and
      128 of 265 in the control group, (RR for virologic failure 0.84, 95% CI 0.71
      0.99; p=0.04). The number needed to treat (NNT) to achieve greater than 95%
      adherence was nine (95% CI 5.0-29.5) and the NNT to achieve viral load
      suppression was 11 (5.8-227.3). INTERPRETATION: Patients who received SMS support
      had significantly improved ART adherence and rates of viral suppression compared
      with the control individuals. Mobile phones might be effective tools to improve
      patient outcome in resource-limited settings. FUNDING: US President's Emergency
      Plan for AIDS Relief.

PMID- 21071075
TI  - Design of culture substrates for large-scale expansion of neural stem cells.
AB  - Neural stem cells (NSCs) have been frequently used to investigate in vitro the
      molecular and cellular mechanisms underlying the development of the central
      nervous system (CNS). In addition, NSCs are regarded as one of the potential
      sources for the cell replacement therapy of CNS disorders. Most of these studies
      have utilized NSCs prepared by neurosphere culture. However, this method normally
      yields a heterogeneous population containing differentiated neural cells as well
      as NSCs. In addition, the rate of cell expansion is not high enough for obtaining
      a large quantity of NSCs in a short period. Here we report the design of culture
      substrates that allow highly selective and rapid expansion of NSCs. We synthesize
      epidermal growth factor fused with a hexahistidine sequence (EGF-His) and a
      polystyrene-binding peptide (EGF-PSt), and these engineered growth factors were
      surface-anchored to a nickel-chelated glass plate and a polystyrene dish,
      respectively. The EGF-His-chelated glass substrate was further used to assemble a
      culture module. Neurosphere-forming cells prepared from the fetal rat striatum
      were used to examine the selective expansion of NSCs using the EGF-His-chelated
      module and the EGF-PSt-bound polystyrene dish. Our results show that the culture
      module enables to selectively expand NSCs in a closed system more efficiently
      than the standard neurosphere culture. The EGF-PSt-bound polystyrene dish also
      permits efficient expansion of NSCs, providing a straightforward means to acquire
      a large quantity of pure NSCs in standard laboratories.

PMID- 21071076
TI  - The healing of full-thickness burns treated by using plasmid DNA encoding VEGF
      165 activated collagen-chitosan dermal equivalents.
AB  - Repair of deep burn by use of the dermal equivalent relies strongly on the
      angiogenesis and thereby the regeneration of dermis. To enhance the dermal
      regeneration, in this study plasmid DNA encoding vascular endothelial growth
      factor-165 (VEGF-165)/N,N,N-trimethyl chitosan chloride (TMC) complexes were
      loaded into a bilayer porous collagen-chitosan/silicone membrane dermal
      equivalents (BDEs), which were applied for treatment of full-thickness burn
      wounds. The DNA released from the collagen-chitosan scaffold could remain its
      supercoiled structure but its degree was decayed along with the prolongation of
      incubation time. The released DNA could transfect HEK293 cells in vitro with
      decayed efficiency too. Human umbilical vein endothelial cells (HUVECs) in vitro
      cultured in the scaffold loaded with TMC/pDNA-VEGF complexes expressed a
      significantly higher level of VEGF and showed higher viability than those
      cultured in the controls, i.e. blank scaffold, and scaffolds loaded with naked
      pDNA-VEGF and TMC/pDNA-eGFP, respectively. The four different BDEs were then
      transplanted in porcine full-thickness burn wounds. Results showed that the
      TMC/pDNA-VEGF group had a significantly higher number of newly-formed and mature
      blood vessels, and fastest regeneration of the dermis. RT-qPCR and western
      blotting found that the experimental group also had the highest expression of
      VEGF, CD31 and alpha-SMA in both mRNA and protein levels. Furthermore, ultra-thin
      skin grafting was performed on the regenerated dermis 14 days later, leading to
      complete repair of the burn wounds with normal histology. Moreover, the tensile
      strength of the repaired tissue increased along with the time prolongation of
      post grafting, resulting in a value of approximately 70% of the normal skin at
      105 days.

PMID- 21071077
TI  - A multimodal nanoparticle-based cancer imaging probe simultaneously targeting
      nucleolin, integrin alphavbeta3 and tenascin-C proteins.
AB  - Molecular imaging of cancers has been characterized based on the sensitivity and
      selectivity of a single cancer probe targeting a cancer biomarker of a specific
      cancer cell line. Here, we designed a multimodal nanoparticle-based
      Simultaneously Multiple Aptamers and RGD Targeting (SMART) cancer probe targeting
      multiple cancer biomarkers to enhance the specificity and signal sensitivity for
      various cancers. Transmission electron microscopy revealed that the multimodal
      SMART cancer probe was spheric and well dispersed. Fluorescence, radioisotope,
      and magnetic resonance analysis demonstrated that the SMART cancer probe
      simultaneously targeting the nucleolin, integrin alpha(v)beta(3) and Tnc proteins
      had dramatically enhanced specificity and signal intensity when used to target
      cancers from C6, NPA, DU145, HeLa and A549 cells when compared with single cancer
      probes conjugated with AS1411, RGD or TTA1 targeting a single cancer biomarker.
      The results demonstrated that the SMART cancer probe will be useful for the
      diagnosis of different cancers as a cancer master probe.

PMID- 21071078
TI  - Hydrogels with time-dependent material properties enhance cardiomyocyte
      differentiation in vitro.
AB  - Tissue-specific elastic modulus (E), or 'stiffness,' arises from developmental
      changes in the extracellular matrix (ECM) and suggests that progenitor cell
      differentiation may be optimal when physical conditions mimic tissue progression.
      For cardiomyocytes, maturing from mesoderm to adult myocardium results in a 9
      fold stiffening originating in part from a change in collagen expression and
      localization. To mimic this temporal stiffness change in vitro, thiolated
      hyaluronic acid (HA) hydrogels were crosslinked with poly(ethylene glycol)
      diacrylate, and their dynamics were modulated by changing crosslinker molecular
      weight. With the hydrogel appropriately tuned to stiffen as heart muscle does
      during development, pre-cardiac cells grown on collagen-coated HA hydrogels
      exhibit a 3-fold increase in mature cardiac specific markers and form up to 60%
      more maturing muscle fibers than they do when grown on compliant but static
      polyacrylamide hydrogels over 2 weeks. Though ester hydrolysis does not
      substantially alter hydrogel stiffening over 2 weeks in vitro, model predictions
      indicate that ester hydrolysis will eventually degrade the material with
      additional time, implying that this hydrogel may be appropriate for in vivo
      applications where temporally changing material properties enhance cell
      maturation prior to its replacement with host tissue.

PMID- 21071079
TI  - A reducible polycationic gene vector derived from thiolated low molecular weight
      branched polyethyleneimine linked by 2-iminothiolane.
AB  - To improve transfection efficiency and reduce the cytotoxicity of polymeric gene
      vectors, reducible polycations (RPC) were synthesized from low molecular weight
      (MW) branched polyethyleneimine (bPEI) via thiolation and oxidation. RPC (RPC
      bPEI(0.8 kDa)) possessed MW of 5 kDa-80 kDa, and 50%-70% of the original proton
      buffering capacity of bPEI(0.8 kDa) was preserved in the final product. The
      cytotoxicity of RPC-bPEI(0.8 kDa) was 8-19 times less than that of the gold
      standard of polymeric transfection reagents, bPEI(25 kDa). Although bPEI(0.8 kDa)
      exhibited poor gene condensing capacities (~2 MUm at a weight ratio (WR) of 40),
      RPC-bPEI(0.8 kDa) effectively condensed plasmid DNA (pDNA) at a WR of 2.
      Moreover, RPC-bPEI(0.8 kDa)/pDNA (WR >=2) formed 100-200 nm-sized particles with
      positively charged surfaces (20-35 mV). In addition, the results of the present
      study indicated that thiol/polyanions triggered the release of pDNA from RPC
      bPEI(0.8 kDa)/pDNA via the fragmentation of RPC-bPEI(0.8 kDa) and ion-exchange.
      With negligible polyplex-mediated cytotoxicity, the transfection efficiencies of
      RPC-bPEI(0.8 kDa)/pDNA were approximately 1200-1500-fold greater than that of
      bPEI(0.8 kDa)/pDNA and were equivalent or superior (~7-fold) to that of bPEI(25
      kDa)/pDNA. Interestingly, the distribution of high MW RPC-bPEI(0.8 kDa)/pDNA in
      the nucleus of the cell was higher than that of low MW RPC-bPEI(0.8 kDa)/pDNA.
      Thus, the results of the present study suggest that RPC-bPEI(0.8 kDa) has the
      potential to effectively deliver genetic materials with lower levels of toxicity.

PMID- 21071080
TI  - Spherical bioactive glass particles and their interaction with human mesenchymal
      stem cells in vitro.
AB  - Sub-micron particles of bioactive glass (SMBGs) with composition 85 mol% SiO(2)
      and 15 mol% CaO were synthesised and characterised. Bioactivity was demonstrated
      by the formation of calcium apatite following 5 days immersion in simulated body
      fluid (SBF). The effect of a 24 h exposure of SMBGs (100 MUg/ml, 150 MUg/ml, 200
      MUg/ml) to human mesenchymal stem cells (hMSCs) on cell viability, metabolic
      activity and proliferation were determined using the LIVE/DEAD, MTT, total DNA
      and LDH assays after 1, 4 and 7 days of culture. None of the SMBG concentrations
      caused significant cytotoxicity at 1 and 4 days, but the doses of 150 and 200
      MUg/ml significantly decreased hMSC metabolic activity after 7 days of culture.
      Cell proliferation decreased as SMBG concentration increased; however none of the
      SMBGs tested had a significant effect on DNA quantity compared to the control.
      Confocal microscopy confirmed cellular uptake and localisation of the SMBGs in
      the hMSC cytoskeleton. Transmission electron microscopy revealed that the SMBGs
      localised inside the cell cytoplasm and cell endosomes. These findings are
      important for assessing the toxicity of sub-micron particles that may either be
      used as injectables for bone regeneration or generated by wear or degradation of
      bioactive glass scaffolds.

PMID- 21071081
TI  - A multicomponent recognition and separation system established via fluorescent,
      magnetic, dualencoded multifunctional bioprobes.
AB  - Accurate and rapid recognition and separation of multiple types of biological
      targets such as molecules, cells, bacteria or viruses from complex sample
      mixtures is of great importance for a wide range of diagnostic and therapeutic
      strategies. To achieve this goal, a set of fluorescent, magnetic, dual-encoded
      multifunctional bioprobes has been constructed by co-embedding different-sized
      quantum dots and varying amounts of gamma-Fe(2)O(3) magnetic nanoparticles into
      swollen poly(styrene/acrylamide) copolymer nanospheres. The dual-encoded
      bioprobes, which possessed different photoluminescent property and magnetic
      susceptibility, were proven to be capable of simultaneously recognizing and
      separating multiple components from a complex sample when three kinds of lectins
      were used as the targets. The lectins were separated with high efficiency and
      kept their bioactivity during the process. Compared to the conventional batchwise
      separation, this method does not require a large number of sequential reaction
      steps, which is economical of time and can be very reagent-saving. By combining
      the multiplexing capability of quantum dots with the superparamagnetic properties
      of iron oxide nanoparticles, this dual-encoded technique is expected to open new
      opportunities in high-throughput and multiplex bioassays, such as cell sorting,
      proteomical and genomical applications, drug screening etc.

PMID- 21071082
TI  - Multivalent niacin nanoconjugates for delivery to cytoplasmic lipid droplets.
AB  - We report here the design, synthesis, and properties, of multifunctional niacin
      nanoconjugates based on dendritic, miktoarm and linear backbone nanocarriers,
      using "click" chemistry. The conjugates were in this instance used to deliver the
      therapeutic agent niacin to lipid droplets. The desired combination of niacin, a
      lipophilic fluorescent dye (BODIPY), and polyethylene glycol (PEG), was achieved
      by covalently linking the desired agents to the selected carrier. The
      nanocarriers containing niacin and BODIPY were found almost exclusively within
      cytoplasmic lipid droplets in the cells used in this study (living hepatocytes
      and microglia), whereas the trifunctional carrier containing niacin, BODIPY and
      PEG was partially localized within these organelles but also elsewhere in the
      cytoplasmic compartment. Spectrofluorometric analyses, confocal microscopy and
      fluorescence cell sorting revealed different rates and extent of multifunctional
      conjugate(s) internalization in the two cell types. Even micromolar
      concentrations of the internalized multifunctional conjugates did not cause
      significant cell death or mitochondrial functional impairment, suggesting that
      they are suitable candidate nanostructures for lipid droplet imaging and for
      targeting drugs to these cellular organelles. These studies provide an efficient
      and easy way to synthesize multifunctional nanocarriers by click chemistry,
      applicable to the synthesis of related multifunctional nanostructures and to
      their use in the targeting of cellular organelles, including lipid droplets.

PMID- 21071083
TI  - In vitro comparison of the photothermal anticancer activity of graphene
      nanoparticles and carbon nanotubes.
AB  - The present study compared the photothermal anticancer activity of near-infrared
      (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower
      NIR-absorbing capacity, suspension of polyvinylpyrrolidone-coated graphene sheets
      exposed to NIR radiation (808 nm, 2 W/cm(2)) generated more heat than DNA or
      sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same
      conditions. Accordingly, graphene nanoparticles performed significantly better
      than CNT in inducing photothermal death of U251 human glioma cells in vitro. The
      superior photothermal sensitivity of graphene sheets could be largely explained
      by their better dispersivity, which has been supported by a simple calculation
      taking into account thermodynamic, optical and geometrical properties of the two
      type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal
      killing of cancer cells apparently involved oxidative stress and mitochondrial
      membrane depolarization resulting in mixed apoptotic and necrotic cell death
      characterized by caspase activation/DNA fragmentation and cell membrane damage,
      respectively.

PMID- 21071084
TI  - The role of collagen receptors Endo180 and DDR-2 in the foreign body reaction
      against non-crosslinked collagen and gelatin.
AB  - Despite the use of collagen-derived scaffolds in regenerative medicine, little is
      known about the degradation mechanisms of these scaffolds in vivo. Non
      crosslinked dermal sheep (NDSC) and gelatin disks were implanted subcutaneously
      in mice. NDSC disks showed a very low degradation rate, despite the presence of
      high numbers of macrophages and the influx of neutrophils. This was attributed to
      the presence of the matrix metalloproteinase inhibitor TIMP-1. The limited
      degradation occurred mainly in the later stages of the foreign body reaction, and
      could be attributed to (1) phagocytosis by macrophages due to a co-expression of
      Endo180 and MT1-MMP on these cells (intracellular degradation) and (2) the
      presence of MMP-13 due to an upregulation of the expression of the DDR-2 receptor
      (extracellular degradation). In contrast, gelatin disks degraded quickly, due to
      the efficient formation of large giant cells as well as the presence of MMP-13;
      the inhibitor TIMP-1 was absent. The DDR-2 receptor was not expressed in the
      gelatin disks. Endo180 and MT1-MMP were expressed, but at most times no co
      expression was seen. We conclude that the physical state of collagen (native or
      denatured) had a dramatic outcome on the degradation rate and provoked a
      completely different foreign body reaction.

PMID- 21071085
TI  - Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays.
AB  - In this paper, we demonstrated that Au nanorods coated with a shell composed of
      Pt nanodots (Au@Pt nanostructures) exhibited intrinsic oxidase-like, peroxidase
      like and catalase-like activity, catalyzing oxygen and hydrogen peroxide
      reduction and the dismutation decomposition of hydrogen peroxide to produce
      oxygen. Based on these findings, we established an Au@Pt nanostructures based
      enzyme linked immunosorbent assay (ELISA) for the detection of mouse interleukin
      2 (IL-2). In comparison with natural enzymes, Au@Pt nanostructures have
      advantages of low cost, easy preparation, better stability, and tunable catalytic
      activity (compared with HRP), which make them a promising enzyme mimetic
      candidate and may find potential applications in biocatalysis, bioassays, and
      nano-biomedicine such as reactive oxygen species (ROS)-related fields (anti-aging
      and therapeutics for neurodegenerative diseases and cancers).

PMID- 21071086
TI  - The influence of environmental exposure on lead concentrations in scalp hair of
      children in Pakistan.
AB  - In the present study the environmental and occupational exposure of Pb has been
      assessed by analyzing the scalp hair (SH) of children (both genders), residing in
      the vicinity of industrial area of Hyderabad, Pakistan. A total of 339 children
      attending primary schools situated in the industrial area, age ranged 5-10 years,
      while for comparative purpose children of the same age group from schools located
      in an area devoid of industries, were selected. The scalp hair was oxidized by
      acid mixture in a microwave oven prior to determination of Pb by graphite furnace
      atomic absorption spectrometry. The concentration profile of Pb in SH of children
      showed that the level changed significantly (44-64%) with changes of living
      habits or environmental exposure. The influence of age, sex, and family
      occupation on the children's hair Pb concentration was also evaluated.
      Significant differences in SH-Pb levels were observed between the exposed (EXC)
      and non-exposed (NEC) children (p<0.01). The concentration of Pb in boys of
      exposed (EX) and non-exposed (NEX) area was more than in girls of the
      corresponding localities. The boys and girls of NEX and EX areas have SH-Pb in
      the range of 3.97-5.4 and 6.06-13.7 MUg g(-1) and 3.41-7.4 and 5.56-11.5 MUg g(
      1), respectively. The Pb levels increased with age in both study groups.

PMID- 21071087
TI  - Molecular epidemiology of Mycobacterium avium subspecies paratuberculosis: IS900
      PCR identification and IS1311 polymorphism analysis from ruminants in the Punjab
      region of India.
AB  - Johne's disease is chronic granulomatous infectious enteritis of animals caused
      by Mycobacterium avium subspecies paratuberculosis. A total of 153 animals from
      19 dairy farms, 2 gaushalas (unproductive-animal rehabilitation centers), 2 goat
      and 2 sheep farms from different districts of the Punjab region were selected on
      the basis of clinical signs of disease. All samples from cattle (n=86), buffalo
      (n=34), goat (n=25) and sheep (n=26) were subjected to Ziehl-Neelsen staining and
      DNA extraction by a freeze and thaw method. Ziehl-Neelsen staining detected 71%
      samples positive for acid-fast bacilli whereas IS900 PCR detected 55% positive
      for Map DNA. IS1311 PCR-REA analysis of IS900 positive samples revealed 'Bison'
      type as the most prevalent (82%) genotype of Map, infecting all domestic
      ruminants. 'Cattle' type was present in a minority of cases (15%) from cattle,
      buffaloes and goats. This is the first report of 'Cattle' type Map from buffalo
      and goat species in India.

PMID- 21071088
TI  - Ficolins and FIBCD1: soluble and membrane bound pattern recognition molecules
      with acetyl group selectivity.
AB  - A network of molecules, which recognizes pathogens, work together to establish a
      quick and efficient immune response to infectious agents. Molecules containing a
      fibrinogen related domain in invertebrates and vertebrates have been implicated
      in immune responses against pathogens, and characterized as pattern recognition
      molecules. Ficolins are soluble oligomeric proteins composed of trimeric collagen
      like regions linked to fibrinogen-related domains (FReDs) that have the ability
      to sense molecular patterns on both pathogens and apoptotic cell surfaces and
      activate the complement system. The ficolins have acetyl-binding properties,
      which have been localized to different binding sites in the FReD-region. A newly
      discovered tetrameric transmembrane protein, FIBCD1, likewise binds acetylated
      structures via the highly conserved FReD. This review presents current knowledge
      on acetyl binding FReD-containing molecules, and discusses structural resemblance
      but also diversity in recognition of acetylated ligands.

PMID- 21071089
TI  - Strain-to-strain difference of V protein of measles virus affects MDA5-mediated
      IFN-beta-inducing potential.
AB  - Laboratory-adapted and vaccine strains of measles virus (MV) induce type I
      interferon (IFN) in infected cells to a far greater extent than wild-type
      strains. We investigated the mechanisms for this differential type I IFN
      production in cells infected with representative MV strains. The overexpression
      of the wild-type V protein suppressed melanoma differentiation-associated gene 5
      (MDA5)-induced IFN-beta promoter activity, while this was not seen in A549 cells
      expressing CD150 transfected with the V protein of the vaccine strain. The V
      proteins of the wild-type also suppressed poly I:C-induced IFN regulatory factor
      3 (IRF-3) dimerization. The V proteins of the wild-type and vaccine strain did
      not affect retinoic acid-inducible gene 1 (RIG-I)- or toll-IL-1R homology domain
      containing adaptor molecule 1 (TICAM-1)-induced IFN-beta promoter activation. We
      identified an amino acid substitution of the cysteine residue at position 272
      (which is conserved among paramyxoviruses) to an arginine residue in the V
      protein of the vaccine strain. Only the V protein possessing the 272C residue
      binds to MDA5. The mutation introduced into the wild-type V protein (C272R) was
      unable to suppress MDA5-induced IRF-3 nuclear translocation and IFN-beta promoter
      activation as seen in the V proteins of the vaccine strain, whereas the mutation
      introduced in the vaccine strain V protein (R272C) was able to inhibit MDA5
      induced IRF-3 and IFN-beta promoter activation. The other 6 residues of the
      vaccine strain V sequence inconsistent with the authentic sequence of the wild
      type V protein barely affected the IRF-3 nuclear translocation. These data
      suggested that the structural difference of laboratory-adapted [corrected] MV V
      protein hampers MDA5 blockade and acts as a nidus for the spread/amplification of
      type I IFN induction. Ultimately, measles vaccine strains have two modes of IFN
      beta-induction for their attenuation: V protein mutation and production of
      defective interference (DI) RNA.

PMID- 21071091
TI  - Prevalence and psychosocial risk factors of PTSD: 18 months after Kashmir
      earthquake in Pakistan.
AB  - BACKGROUND: On average in a year 939 earthquakes of a magnitude between 5 and 8
      on the Richter scale occur around the world. In earthquakes developing countries
      are prone to large-scale destruction because of poor structural quality of
      buildings, and preparedness for earthquakes. On 8th October 2005, a major
      earthquake hit the remote and mountainous region of northern Pakistan and
      Kashmir. We wanted to find out the rate of PTSD in a randomly selected sample of
      participants living in earthquake area and the correlates of the PTSD. METHOD:
      The study was conducted 18 months after the earthquake. We selected a sample of
      men and women living in the houses and tents for interviews. Using well
      established instruments for PTSD and general psychiatric morbidity we gathered
      information from over 1200 people in face to face interviews. We gathered
      information about trauma exposure and loss as well. RESULTS: 55.2% women and
      33.4% men suffered from PTSD. Living in a joint family was protective against the
      symptoms of PTSD. Dose of exposure to trauma was associated with the symptoms of
      PTSD. Living in a tent was associated with general psychiatric morbidity but not
      with PTSD. LIMITATIONS: We used questionnaire instead of interviews to detect the
      symptoms of psychiatric disorders. CONCLUSIONS: The symptoms of PTSD are common
      18 months after the earthquake and they are specifically associated with the dose
      of trauma exposure. This may have implications for rehabilitation of this
      population.

PMID- 21071090
TI  - An associative learning deficit in 1-year-old infants of depressed mothers: role
      of depression duration.
AB  - The effectiveness of infant-directed speech (IDS) produced by non-depressed
      mothers for promoting the acquisition of voice-face associations was investigated
      in 1-year-old children of depressed mothers in a conditioned-attention paradigm.
      Prior research suggested that infants of mothers with comparatively longer
      duration depressive episodes exhibit poorer learning in response to non-depressed
      mothers' IDS, but duration of depression was confounded with infant age. In the
      current study, 1-year-old infants of currently depressed mothers with relatively
      longer-duration depressive episodes (i.e., perinatal onset) showed significantly
      poorer learning than 1-year-olds of currently depressed mothers with relatively
      shorter duration depressive episodes (non-perinatal onset). This was true despite
      the fact that there were no measurable differences in the severity of depression,
      level of social functioning, or antidepressant medication use between the two
      groups. These findings add support to the hypothesis that there is an experience
      based change in responsiveness to female IDS in infants of depressed mothers
      during the first year of life.

PMID- 21071092
TI  - Prevalence and predictors of suicidal behaviour in a sample of adults with
      estimated borderline intellectual functioning: results from a population survey.
AB  - BACKGROUND: We aimed to investigate, for the first time, rates of suicidal
      behaviour (ideation and acts) in people with borderline intellectual functioning
      in a general population sample, and to compare these to rates in people with
      normal functioning. METHODS: We used data from the third Adult Psychiatric
      Morbidity Survey, carried out in England in 2007. It was designed to be
      representative of people living in private households. The analyses are based on
      6872 individuals. RESULTS: 1053 (16.1%) participants met criteria for borderline
      intellectual functioning. People with borderline intellectual functioning were
      more likely to report ever having made a suicidal attempt or to have harmed
      themselves without the intention of taking their own life (Odds Ratio for both
      1.7, 95% Confidence Interval 1.3-2.2). These associations were no longer
      significant after controlling for income and age. LIMITATIONS: Our sample did not
      include people living in segregate environments, who were likely to display
      challenging behaviours, and have higher rates of self harm. CONCLUSION: The
      increased rates of suicidal behaviour found in people with borderline
      intellectual functioning were explained by younger age and socioeconomic
      disadvantages, although the association is likely to be complex. Our findings
      would strongly support targeting those at the lower range of intelligence with
      interventions for suicide prevention.

PMID- 21071093
TI  - Clinical correlates of eating disorder comorbidity in women with bipolar disorder
      type I.
AB  - OBJECTIVE: To report on the presence of current and lifetime eating disorders
      (ED) in a well-defined sample of 137 female individuals with bipolar disorder
      type I. METHODS: Trained psychiatrists interviewed the patients, and the
      diagnoses of BD and comorbidities were confirmed using the Structured Clinical
      Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis I
      Disorders. Clinical and demographic characteristics of both groups (group with ED
      vs. group without ED) were compared. RESULTS: Female patients with ED had an
      earlier onset of BD and an increased number of mood episodes, predominantly
      depressive. Women in the ED group also had higher rates of comorbidity with
      substance use disorders and anxiety disorders and reported a history of suicide
      attempts more frequently than women without ED. CONCLUSION: The presence of ED is
      a correlate of severity of BD type I, and interventions should be developed to
      minimize distress and suicide risk and to improve treatment outcome.

PMID- 21071094
TI  - Biased emotional recognition in depression: perception of emotions in music by
      depressed patients.
AB  - BACKGROUND: Depression is a highly prevalent mood disorder, that impairs a
      person's social skills and also their quality of life. Populations affected with
      depression also suffer from a higher mortality rate. Depression affects person's
      ability to recognize emotions. We designed a novel experiment to test the
      hypothesis that depressed patients show a judgment bias towards negative
      emotions. METHODS: To investigate how depressed patients differ in their
      perception of emotions conveyed by musical examples, both healthy (n=30) and
      depressed (n=79) participants were presented with a set of 30 musical excerpts,
      representing one of five basic target emotions, and asked to rate each excerpt
      using five Likert scales that represented the amount of each one of those same
      emotions perceived in the example. RESULTS: Depressed patients showed moderate
      but consistent negative self-report biases both in the overall use of the scales
      and their particular application to certain target emotions, when compared to
      healthy controls. Also, the severity of the clinical state (depression, anxiety
      and alexithymia) had an effect on the self-report biases for both positive and
      negative emotion ratings, particularly depression and alexithymia. LIMITATIONS:
      Only musical stimuli were used, and they were all clear examples of one of the
      basic emotions of happiness, sadness, fear, anger and tenderness. No neutral or
      ambiguous excerpts were included. CONCLUSIONS: Depressed patients' negative
      emotional bias was demonstrated using musical stimuli. This suggests that the
      evaluation of emotional qualities in music could become a means to discriminate
      between depressed and non-depressed subjects. The practical implications of the
      present study relate both to diagnostic uses of such perceptual evaluations, as
      well as a better understanding of the emotional regulation strategies of the
      patients.

PMID- 21071095
TI  - Requiring both avoidance and emotional numbing in DSM-V PTSD: will it help?
AB  - OBJECTIVE: The proposed DSM-V criteria for posttraumatic stress disorder (PTSD)
      specifically require both active avoidance and emotional numbing symptoms for a
      diagnosis. In DSM-IV, since both are included in the same cluster, active
      avoidance is not essential. Numbing symptoms overlap with depression, which may
      result in spurious comorbidity or overdiagnosis of PTSD. This paper investigated
      the impact of requiring both active avoidance and emotional numbing on the rates
      of PTSD diagnosis and comorbidity with depression. METHOD: We investigated PTSD
      and depression in 835 traumatic injury survivors at 3 and 12 months post-injury.
      We used the DSM-IV criteria but explored the potential impact of DSM-IV and DSM-V
      approaches to avoidance and numbing using comparison of proportion analyses.
      RESULTS: The DSM-V requirement of both active avoidance and emotional numbing
      resulted in significant reductions in PTSD caseness compared with DSM-IV of 22%
      and 26% respectively at 3 and 12 months posttrauma. By 12 months, the rates of
      comorbid PTSD in those with depression were significantly lower (44% vs. 34%)
      using the new criteria, primarily due to the lack of avoidance symptoms.
      CONCLUSION: These preliminary data suggest that requiring both active avoidance
      and numbing as separate clusters offers a useful refinement of the PTSD
      diagnosis. Requiring active avoidance may help to define the unique aspects of
      PTSD and reduce spurious diagnoses of PTSD in those with depression.

PMID- 21071096
TI  - Clinical value of early partial symptomatic improvement in the prediction of
      response and remission during short-term treatment trials in 3369 subjects with
      bipolar I or II depression.
AB  - OBJECTIVE: To evaluate the clinical value of early partial symptomatic
      improvement in predicting the probability of response during the short-term
      treatment of bipolar depression. METHODS: Blinded data from 10 multicenter,
      randomized, double-blind, placebo-controlled trials in bipolar I or II depression
      were used to determine if early improvement (>=20% reduction in depression
      symptom severity after 14 days of treatment) predicted later short-term response
      or remission. Sensitivity, specificity, efficiency, and positive and negative
      predictive values (PPV, NPV) were calculated using an intent to treat analysis of
      individual and pooled study data. RESULTS: 1913 patients were randomized to
      active compounds (aripiprazole, lamotrigine, olanzapine/olanzapine-fluoxetine,
      and quetiapine), and 1456 to placebo. In the pooled positive studies, early
      improvement predicted response and remission with high sensitivity (86% and 88%,
      respectively), but rates of false positives were high (53% and 59%,
      respectively). Pooled negative predictive values for response/remission (i.e.
      confidence in knowing the drug will not result in response or remission) were 74%
      and 82%, respectively, with low rates of false negatives (14% and 12%,
      respectively). CONCLUSION: Early improvement in an individual patient does not
      appear to be a reliable predictor of eventual response or remission due to an
      unacceptably high false positive rate. However, the absence of early improvement
      appears to be a highly reliable predictor of eventual non-response, suggesting
      that clinicians can have confidence in knowing when a drug is not going to work
      during short-term treatment. Patients who fail to demonstrate early improvement
      within the first two weeks of treatment may benefit from a change in therapy.

PMID- 21071097
TI  - Association between major mood disorders and the hypocretin receptor 1 gene.
AB  - BACKGROUND: Recent studies suggested a role for hypocretins in the neurobiology
      of Major Mood Disorders (MMD). The purpose of this study was to investigate
      hypocretin involvement in MMD evaluating whether particular alleles or genotypes
      of the hypocretin pathway genes (HCRT, HCRTR1 and HCRTR2) would modify the
      occurrence and clinical features of the disease. METHODS: We selected for the
      study 229 MMD patients and 259 healthy age-, sex- and ethnicity-matched controls.
      Cases and controls were genotyped for several single-nucleotide polymorphisms
      (SNPs) of the HCRT, HCRTR1, and HCRTR2 genes. RESULTS: We found that allelic and
      genotypic frequencies of the rs2271933 G>A polymorphism (Ile408Val) in the HCRTR1
      gene were significantly different between cases and controls (p=0.003 and
      p=0.0004, respectively). The carriage of the A allele was associated with a
      significantly increased disease risk (OR:1.60, 95% C.I. 1.22-2.10). In addition,
      we found a significant association between HCRTR1 haplotypes and the disease
      (permutation p<0.0001). In the analysis of subgroups we confirmed the association
      only in patients with unipolar depression. LIMITATIONS: Our sample was relatively
      small and included only cases and controls recruited from Northern Italy.
      Analysis of the disease subgroups warrants reexamination with more subjects.
      Finally, the effects of the rs2271933 G>A polymorphism on the hypocretin-1
      receptor function are unknown. CONCLUSIONS: Our study suggests that the HCRTR1
      gene or a linked locus may modulate the risk for Major Mood Disorders and
      supports recent studies suggesting an involvement of hypocretin neurotransmitter
      system in affective disorders.

PMID- 21071098
TI  - Psychosocial dwarfism: psychopathological aspects and putative neuroendocrine
      markers.
AB  - There exists an extensive terminology for defining the situation of children who,
      in varying circumstances, suffer from affective deprivation (AD), within an
      unsatisfactory family situation or in institutions. Nevertheless, the
      neuroendocrine mechanisms (if they exist) determining it have yet to be
      identified. Our objective was to determine if specific neuroendocrine markers,
      all of them previously implicated in affective disorders, could be modified, and
      in which sense, in affective deprivation syndrome of the child. For this purpose,
      we studied three separate groups of children: (1) control group (CG); (2)
      children suffering from AD; and (3) children with non-organic failure to thrive
      (NOFT). In every case, we studied the serum levels of melatonin, serotonin, beta
      endorphins and adrenocorticotropic hormone (ACTH); and kynurenine pathway
      tryptophan metabolites (both during the day and at night). Significantly, there
      was a conspicuous reduction in the levels of each of the neuroendocrine markers
      (melatonin, serotonin, beta-endorphins and ACTH) in the group suffering from
      affective deficiency, a diminution which was even more noticeable in the group of
      patients presenting delayed growth. Furthermore, as also occurs in other
      affective disorders, there were corresponding modifications in the metabolisation
      of tryptophan. We report the existence of neuroendocrine mechanisms that are
      associated with the above-mentioned clinical manifestations in these patients,
      mechanisms that may underlie the close connection existing between AD syndrome
      and the cause of NOFT. These data suggest that the AD syndrome and NOFT comprise
      a single process, but one with a different evolutionary continuum of psychosocial
      dwarfism.

PMID- 21071099
TI  - Implementation of a manual-based training of humor abilities in patients with
      depression: a pilot study.
AB  - Humor and laughter can positively influence mood, promote optimism and lead to a
      change of perspective. Six patients with major depression participated in a group
      training program specifically designed to enhance humor abilities. After 8 weeks
      of training, short-term mood improvement was observed and the patients considered
      themselves more capable of using humor as a coping strategy. Acquired humor
      skills also helped to sustain the patients' motivation throughout the training
      period. In light of these encouraging findings, further studies to compare the
      effectiveness of the humor training with the effectiveness of other types of
      intervention and to assess its potential long-term effects seem warranted.

PMID- 21071100
TI  - Selective cloning, characterization, and production of the Culicoides nubeculosus
      salivary gland allergen repertoire associated with equine insect bite
      hypersensitivity.
AB  - Salivary gland proteins of Culicoides spp. have been suggested to be among the
      main allergens inducing IgE-mediated insect bite hypersensitivity (IBH), an
      allergic dermatitis of the horse. The aim of our study was to identify, produce
      and characterize IgE-binding salivary gland proteins of Culicoides nubeculosus
      relevant for IBH by phage surface display technology. A cDNA library constructed
      with mRNA derived from C. nubeculosus salivary glands was displayed on the
      surface of filamentous phage M13 and enriched for clones binding serum IgE of IBH
      affected horses. Ten cDNA inserts encoding putative salivary gland allergens were
      isolated and termed Cul n 2 to Cul n 11. However, nine cDNA sequences coded for
      truncated proteins as determined by database searches. The cDNA sequences were
      amplified by PCR, subcloned into high level expression vectors and expressed as
      hexahistidine-tagged fusion proteins in Escherichia coli. Preliminary ELISA
      results obtained with these fusions confirmed the specific binding to serum IgE
      of affected horses. Therefore, the putative complete open reading frames derived
      from BLAST analyses were isolated by RACE-PCR and subcloned into expression
      vectors. The full length proteins expressed in Escherichia coli showed molecular
      masses in the range of 15.5-68.7 kDa in SDS-PAGE in good agreement with the
      masses calculated from the predicted protein sequences. Western blot analyses of
      all recombinant allergens with a serum pool of IBH-affected horses showed their
      ability to specifically bind serum IgE of sensitized horses, and ELISA
      determinations yielded individual horse recognition patterns with a frequency of
      sensitization ranging from 13 to 57%, depending on the allergen tested. The in
      vivo relevance of eight of the recombinant allergens was demonstrated in
      intradermal skin testing. For the two characterized allergens Cul n 6 and Cul n
      11, sensitized horses were not available for intradermal tests. Control horses
      without clinical signs of IBH did not develop any relevant immediate
      hypersensitivity reactions to the recombinant allergens. The major contribution
      of this study was to provide a repertoire of recombinant salivary gland allergens
      repertoire from C. nubeculosus potentially involved in the pathogenesis of IBH as
      a starting basis for the development of a component-resolved serologic diagnosis
      of IBH and, perhaps, for the development of single horse tailored specific
      immunotherapy depending on their component-resolved sensitization patterns.

PMID- 21071101
TI  - Status of newborn hearing screening program in India.
AB  - OBJECTIVES: The present study is aimed at figuring out the status of new-born
      hearing screening program being conducted in India, estimate the use of different
      screening instruments used and tests practiced, study the role of various
      professionals involved and document the current practices of audiologists in the
      country. METHOD: A questionnaire on "Newborn Hearing Screening Survey" was sent
      to 185 institutions (165 medical colleges and 20 Speech and hearing centers) all
      over India and the information gathered was subjected to appropriate analyses.
      RESULTS: On a 16.75% return rate of the questionnaire, almost half of the
      colleges have their annual birthing census more than 2000. The majority of sites
      (57.13%) report an average length of stay for a vaginal delivery to be more than
      24 hours with 78.94% also reporting of a NICU of Level II/III type. Only 38.09%
      of the medical colleges have a universal Newborn Hearing screening program (NBHS)
      in comparison to 80% of the Speech and Hearing centers. Again 43.8% of the
      medical colleges who conduct NBHS program have an audiologist and majority of
      them work towards screening. Almost 63% of the speech and hearing centers use
      physiological tests like ABR, OAE or their combination to screen newborns. Both
      medical and speech and hearing organizations prefer that the audiologist inform
      and even give a written material regarding the results of the tests to the
      parents. Only 62.65% of the institutions refer less than 11% of their clients for
      further testing at the time of discharge. In 50% of the medical colleges the
      results of a test are reported to the parents and primary care physicians/doctors
      and in 37.5% of the speech and hearing centers the results are informed to the
      parents. CONCLUSIONS: While keeping in mind the incidence of hearing impairment
      in the neonatal population of India, the results of this survey warrant the need
      for an urgent implementation of universal neonatal hearing screening in all the
      health care facilities in the country, at large.

PMID- 21071102
TI  - Evaluating diagnostic strategy of older patients with unexplained unintentional
      body weight loss: a hospital-based study.
AB  - Unexplained unintentional weight loss (UUWL) is a common health problem in older
      adults, and raises significant diagnostic challenges. Currently, there is no
      consensus or guideline to help physicians approach these patients. The main
      purpose of this study is to evaluate physicians' behaviors in evaluating elderly
      patients with UUWL and to compare the diagnostic strategy of internists and
      geriatricians. From January of 2008 to December of 2009, medical records of all
      elderly patients admitted to Taipei Veterans General Hospital with UUWL were
      obtained for study. All diagnostic procedures used during admissions were
      evaluated and the final diagnosis for each patient was obtained. Overall, data of
      136 patients (mean age: 79.8+/-6.3 years, 80.9% males) were obtained for study
      with their mean weight loss of 8.6+/-6.4 kg. Among them, 79 (58.1%) patients were
      admitted to the geriatric evaluation and management unit (GEMU) and 57 (41.9%)
      patients were admitted to the general medical wards. There were no statistically
      significant differences in terms of age, sex, mean age and average weight loss
      between these two groups. After extensive diagnostic effort, the most common
      diagnostic entity was benign organic disease (33.8%), followed by unknown
      (25.7%), neuropsychiatric disorder (23.5%), and malignancy (16.9%). Tumor markers
      are commonly used, including carcinoembryonic antigen (CEA) (80.9%), prostate
      specific antigen (PSA) (81.8%), and carbohydrate 19-9 (CA 19-9) (65.4%). Imaging
      studies were also commonly used diagnostic tools, including gastrointestinal
      endoscopy (70.6%), colonoscopy (42.6%) and computerized tomography (44.1%).
      Compared with internists, geriatricians were more likely to order PSA testing
      (70.5% vs. 89.4%, p=0.021). In contrast, internists were more likely to order CA
      199 (75.4%% vs. 58.2%, p=0.045), and to arrange gastrointestinal endoscopy than
      geriatricians (82.4% vs. 62.0%%, p=0.013). In conclusion, cancer accounts for
      only 16.9% of all elderly patients with UUWL in this study, tumor markers are
      very commonly used for screening of occult cancer. Compared with internists,
      geriatricians are more likely to order PSA and to establish neuropsychiatric
      diagnosis, and internists are more prone to order carbohydrate (CA 19-9) and
      gastrointestinal endoscopy.

PMID- 21071103
TI  - Herd-level risk factors for antimicrobial demanding gastrointestinal diseases in
      Danish herds with finisher pigs: A register-based study.
AB  - Endemic gastrointestinal (GI) diseases have a substantial negative impact on pig
      production, because, when present, they reduce animal welfare, productivity and
      generate high antimicrobial (AM) demand. In Danish legislation, AM can be
      prescribed only for therapeutic purposes. The objective of the study was to
      estimate the association between herd-level risk factors and the amount of AM use
      (AMU) in connection with GI diseases in finisher herds. We conducted a register
      based cross-sectional study with repeated measurements from 2004 to 2007. Data
      were extracted from databases in the Danish Register of Veterinary Medicine, the
      Central Husbandry Register and the Danish Agriculture and Food Council. In total,
      3192 pig herds with 26,973 records (quarters with prescriptions) were included.
      The outcome was presented as average AM use (measured as Animal Daily Dosage) for
      GI diseases per finishing pig per quarter per herd. Three potential herd-level
      risk factors were evaluated: herd size (number of finishers delivered for
      slaughter); herd health status (herds in the Specific Pathogen Free (SPF) System,
      conventional herds); and herd type (herds including only finishers, integrated
      herds). Data were analyzed using general linear mixed models with repeated
      measurements. Smaller herds had a larger AMU per finisher than larger herds.
      Integrated herds had lower AMU as compared with herds with only finishers. Herds
      within the SPF System had a larger decrease in AMU with increasing herd size
      compared to conventional herds. Significant regional differences in AMU were
      seen. Additionally, the results showed that other herd factors and veterinarians
      were more influential than the investigated herd risk factors. This illustrates
      the difficulties of characterising AM-demanding GI diseases in herds by the use
      of register data only.

PMID- 21071104
TI  - Risk evaluation of nonvaccinated, weaned calves transported through areas under
      systematic foot and mouth disease (FMD) vaccination.
AB  - The recurrence and persistence of foot and mouth disease (FMD) could be the
      consequence of cyclic and massive transportation of calves. For this reason, in
      South America, vaccination strategies related to livestock dynamic are being
      promoted. In order to aid the evaluation of such strategies, a method for
      predicting the risk of transportation of nonvaccinated weaned calves was
      developed; this method combines expert opinion and empirical evidence using
      Bayesian estimators. It was applied through Monte Carlo simulation to data of
      Argentina under four hypothetical vaccination schemes: E1, extended vaccination
      season of 1/6 of the population of calves each month from July to December
      without second round vaccination (SRV); E2, extended irregular vaccination from
      July to December with SRV applied to 70% of the calves resembling the scheme
      applied in Argentina in 2001; E3, vaccination in November and December without
      SRV; and E4, vaccination concentrated in November. E1 resulted in probability of
      transporting non vaccinated calves (tnvc) reaching its maximum in the following
      year in May with mean=0.0250 and percentile 95% (P95)=0.0404; for the same month
      tnvc estimates for the other schemes were E2: mean=0.0071; P95=0.0162; E3:
      mean=0.0017; P95=0.0042 and E4: mean=0.0001; P95=0.0004. Bonferroni multiple
      comparison for simultaneous assertions for May showed that E4 resulted the best
      scheme, E1 the worst, and E2 and E3 are intermediate with nonsignificant
      difference observed between overall (p<0.05). Results were consistent with
      historical records and quantification for future needs for re-vaccination was
      made possible. While the ratio "total vaccinated"/"total estimated existences"
      will give a biased vision of vaccination coverage under the situation of extended
      vaccination campaigns, a model as the one developed here could allow a more
      accurate assessment and the design of mitigation plans.

PMID- 21071105
TI  - The CYP51C gene, a reliable marker to resolve interspecific phylogenetic
      relationships within the Fusarium species complex and a novel target for species
      specific PCR.
AB  - Early diagnosis and control of different Fusarium species is essential for
      successful management of plant disease and subsequent prevention of toxins
      entering the food chain. This issue can be addressed using phylogenetic analyses
      and other molecular techniques, including the design of species-specific primers
      and corresponding PCR assays. In practice, only a few genes are sequenced for
      most species and insights into the evolutionary mechanisms at the species level
      usually stem from phylogenetic analyses of only one or a small number of genetic
      loci. This poses the question of whether the recovered tree accurately reflects
      the relationships among species or rather more local interrelationships
      particular to the genetic marker employed. This study examined if the Fusarium
      specific CYP51C gene can be used to establish evolutionary relationships between
      Fusarium species and enable species-specific detection. The resolving power of
      the CYP51C gene was studied for 46 Fusarium isolates representing 18 different
      species. The resulting phylogeny analysis showed clear and well-structured
      separation of the isolates according to their species rank, synthesised toxin and
      Fusarium section. Moreover, a comparison between the individual CYP51C phylogeny
      and a reference tree (inferred from the concatenation of ITS, CYP51C, beta
      tubulin and TEF-1alpha sequences) indicated superior resolution of CYP51C
      relative to ITS and beta-tubulin sequences. In addition to its suitability as a
      reliable marker for diagnosis of different toxigenic Fusarium species, we also
      show that the CYP51C gene is a promising target for development of species
      specific PCR. This was demonstrated by the specific detection of Fusarium
      cerealis in grain samples of wheat.

PMID- 21071106
TI  - "We charge them; otherwise we cannot run the hospital" front line workers,
      clients and health financing policy implementation gaps in Ghana.
AB  - OBJECTIVES: This paper examines policy implementation gaps of user fees plus
      exemptions and health insurance in providing financial access to primary clinical
      care for children under five in Ghana. METHODS: Methods included analysis of
      routine data, focus group discussions, in-depth interviews, and administration of
      a structured questionnaire. RESULTS: Providers modified exemptions policy
      implementation arrangements, sometimes giving partial or no exemptions. Clients
      who knew or suspected exemption entitlements failed to request them because of
      fear of negative reactions from providers. Providers attributed their
      modification of implementation arrangements and negative reactions to the threat
      posed to the financial viability of their institutions by reimbursement
      uncertainty and delays. At the time of the study insurance coverage was low and
      frontline workers were not noticeably modifying implementation arrangements.
      However, the underlying goal conflicts, resource scarcity, conditions of work and
      relationships between frontline workers and clients that fueled the exemptions
      policy implementation gaps were unchanged. The potential for the health insurance
      policy to stumble over implementation gaps as happened with the exemptions policy
      therefore remained. CONCLUSIONS: Policies that do not take into account the
      incentives for frontline worker adherence and align them better with policy
      objectives may experience implementation gaps.

PMID- 21071107
TI  - Health technology prioritization: which criteria for prioritizing new
      technologies and what are their relative weights?
AB  - OBJECTIVES: To review the criteria and 'other' considerations used
      internationally for prioritizing new health technologies, and to demonstrate a
      conjoint-analysis methodology (also known as discrete choice experiments) for
      deriving relative weights for the criteria. METHODS: We searched the literature
      for criteria and other considerations for prioritizing new technologies. A
      convenience sample of 74 respondents completed a conjoint-analysis survey
      involving criteria related to technologies' 'benefits'. RESULTS: Encompassing 11
      countries and the US state of Oregon, we were able to distinguish three main
      groups of criteria: (a) Need, appropriateness and clinical benefits; (b)
      Efficiency (including cost-effectiveness); and (c) Equality, solidarity and other
      ethical or social values. For several countries, the quality of the clinical and
      economic evidence and factors related to strategic issues and procedural justice
      respectively are also considered. The criteria and their weights from the
      conjoint-analysis survey are: 'Lives saved'=0.343, 'Life-prolongation
      benefits'=0.243, 'Quality-of-life gains'=0.217, a criterion representing the
      availability of alternative treatments=0.107, and 'Other important social/ethical
      benefits'=0.087. CONCLUSIONS: The criteria represent a pluralistic combination of
      needs-based, maximizing and egalitarian principles, and we demonstrated a
      methodology for deriving the weights for criteria related to technologies'
      'benefits'.

PMID- 21071109
TI  - Surgery and mesothelioma: if not randomization, at least standardization and
      registration!

PMID- 21071108
TI  - Availability of a newly devised ambulatory urodynamics monitoring system based on
      personal device assistance in patients with spinal cord injury.
AB  - Conventional urodynamics systems have been widely used for the assessment of
      bladder functions. However, they have some drawbacks due to the unfamiliar
      circumstances for the patient, restrictive position during the test, expense and
      immovability of the instrument as well as the unphysiological filling of the
      bladder. To mitigate these problems, we developed a fully ambulatory urodynamics
      monitoring system, which enables the abdominal pressure to be measured in a non
      invasive manner, as well as the manual recording of various events such as the
      bladder sensations or leakage of urine. Conventional (CMG) and furosemide
      stimulated filling cystometry (FCMG) were performed for 28 patients with
      neurogenic bladders caused by spinal cord injury (24 males and 4 females, age:
      49.4 +/- 13.9 years, BMI: 23.5 +/- 2.4). There were high correlation coefficients
      (r=0.97 +/- 0.02) between the clinical parameters measured by the conventional
      rectal catheter and those measured by our non-invasive algorithm in the FCMG
      studies. Also, 10 of the patients (36%) were diagnosed as having different
      reflexibility of the bladder between conventional CMG and FCMG (p<0.05). In the
      patients with detrusor overactivity, the average volume and detrusor pressure at
      bladder sensation in FCMG were lower than those in CMG, while the average
      compliance was higher (p<0.05). In the patients with areflexic bladders, the
      number of patients with detrusor overactivity was higher in FCMG and leakage was
      observed more frequently. These results showed that our system could be a useful
      additional tool in the clinical assessment of patients in which conventional
      cystometry failed to explain their symptoms.

PMID- 21071110
TI  - Ethylene-regulated (methylsulfanyl)alkanoate ester biosynthesis is likely to be
      modulated by precursor availability in Actinidia chinensis genotypes.
AB  - The limiting steps of ethylene-dependent (methylsulfanyl)alkanoate ester
      biosynthesis have been investigated in this study, using closely related
      Actinidia chinensis genotypes and the commercial cultivar 'Hort16A'.
      Quantification of methylsulfanyl-compounds from the headspace of ethylene
      producing kiwifruits revealed little variation in their volatile composition but
      remarkable differences in the magnitude of the fruit volatile levels. To test
      whether the variations in fruit volatile levels can be correlated with the
      genotype-specific apparent catalytic efficiency, the initial slope of the
      substrate response curve (V'(Max)K(M)(-1) where V'(Max) is the apparent V(Max) in
      a crude extract) was evaluated for total alcohol acyltransferase (EC 2.3.1.84)
      activity. The V'(Max)K(M)(-1) values of different (methylsulfanyl)alkyl-CoAs were
      in a similar range for most genotypes, which suggests substrate availability as
      the limiting factor for (methylsulfanyl)alkanoate ester synthesis in these
      kiwifruit. Furthermore, gene expression analysis of acyltransferase expressed
      sequence tags points towards the action of multiple isozymes for
      (methylsulfanyl)alkanoate ester synthesis, emphasizing the central role of
      substrate levels on final ester concentrations. Volatile levels of the potential
      precursor methional were increased in ethylene-producing A. chinensis kiwifruit
      and a close connection between (methylsulfanyl)alkanoate ester formation and
      ethylene synthesis in plants is proposed. Finally, a possible biosynthetic
      pathway is presented.

PMID- 21071111
TI  - [Relationship between aging stereotypes and performance in a cognitive
      stimulation program].
AB  - INTRODUCTION: The main goal of the current research was to study the relationship
      between holding negative aging stereotypes and cognitive performance in a
      cognitive stimulation program in an older adult group (n=55) with Mild Cognitive
      Impairment. MATERIAL AND METHODS: Performance and stereotypes were contrasted
      before and after the cognitive stimulation program. RESULTS: Firstly, results
      showed a significant improvement in associative learning and verbal recall, as
      well as significant stereotypes score reduction after treatment. Secondly, those
      who improved their associative learning performance had a higher stereotypes
      score before the program. Even though, this group also reduced their stereotype
      score. CONCLUSIONS: These findings show that people who improve their cognitive
      performance also reduce their stereotypes score. This relationship is very novel,
      because although the correlation between absence of stereotype and better
      cognitive performance has been found in the literature, a positive correlation
      between stereotype change and cognitive performance after a psychological
      treatment has not been observed before.

PMID- 21071112
TI  - [Community health: integration of primary care and public health competencies.
      SESPAS report 2010].
AB  - Primary care and public health have run on parallel tracks with scarce points of
      contact or coordination in community action to improve the population's health.
      If community health is defined as the "health of individuals and groups in a
      defined community, determined by the interaction of personal and familial factors
      and by the socioeconomic-cultural and physical environments" and of community
      intervention is defined as local action to improve community health, primary care
      and public health are the key players to implement this aim. However, their
      actions should take into account other local actors, including the population.
      The inclusion of community health as an objective of the health system highlights
      the need to achieve more coordinated and comprehensive action, and to introduce
      advances in several areas, which include training for health professionals,
      contracts to service providers, systems for defining service portfolios, and
      organizational aspects of services.

PMID- 21071113
TI  - Discovery of a novel nitroimidazolyl-oxazolidinone hybrid with potent anti Gram
      positive activity: Synthesis and antibacterial evaluation.
AB  - A number of linezolid analogues containing a nitroaryl-1,3,4-thiadiazole moiety,
      were prepared and evaluated as antibacterial agents against a panel of Gram
      positive and Gram-negative bacteria. Among synthesized compounds, nitrofuran
      analogue 1b exhibited more potent inhibitory activity, with respect to other
      synthesized compounds and reference drug linezolid. The target compounds were
      also assessed for their cytotoxic activity against normal mouse fibroblast
      (NIH/3T3) cells using MTT assay. The results indicated that compound 1c exhibit
      potent antibacterial activity against Gram-positive bacteria at non-cytotoxic
      concentrations.

PMID- 21071114
TI  - Improving teaching strategies in an undergraduate community health nursing (CHN)
      program: implementation of a service-learning preceptor program.
AB  - A service-learning component was added to the existing preceptor practicum
      program at the University of North Carolina Charlotte's School of Nursing (UNCC
      SON) in the fall of 2007 for nursing students in the community health nursing
      (CHN) practicum course. OBJECTIVE: The preceptorship model is commonly used in
      undergraduate nursing education. The aim of this study was to improve teaching
      strategies in the existing school health nursing (SHN) preceptor program by the
      addition of a service-learning community partnership. Adding the service-learning
      component was based on the Polvika model. PARTICIPANTS: A total of 27 nursing
      students and 33 preceptors participated in the study. DATA ANALYSIS: Percentages,
      means, standard deviations, and rankings were used to analyze the data. The
      participants completed a multiple-choice survey and ranked a list of tasks.
      RESULTS: The students were able to fulfill their task responsibilities, and the
      service-learning preceptor program was cost effective for the SHN preceptors
      through hours saved by the nursing students. CONCLUSION: The preceptor role is
      associated with many factors, including perceived burden, which affects their
      willingness to work with students. The findings demonstrated that service
      learning is an effective teaching strategy in the CHN nursing students' learning
      by fostering the preceptors' benefits, rewards, support, and commitment to the
      role.

PMID- 21071115
TI  - Towards culturally relevant nursing education for aboriginal students.
AB  - Aboriginal nursing students face numerous challenges in North American nursing
      educational programs, as reflected in the relatively high attrition rate of these
      students. In this paper, the authors argue that nurse educators need to create
      more culturally relevant curriculum and instructional approaches for Aboriginal
      students. Such approaches would help nursing educators to ensure that current
      aboriginal nursing programs--which are largely assimilative in nature--can be
      more successful and transformative in nature.

PMID- 21071116
TI  - Determination of 226Ra and 228Ra in slightly mineralised natural waters.
AB  - A radiochemical method for simultaneous separation of (226)Ra and (228)Ra from
      natural waters by precipitating the radionuclides in the form of chromates that
      have low solubility in weak acetic acid has been described. For analytical
      purposes the change into soluble state was achieved through high-temperature
      melting the radium chromates precipitate with sodium and potassium carbonates at
      certain ratios. The chemical yield for radium-226 amounted to 87.1 +/- 1.4% at
      the efficiency of counting 92.8 +/- 0.7%. Calculated in series of 20 parallel
      determinations, reproducibility of the method was 7%. The chemical yield in
      separating radium-228 made up 63.8 +/- 1.1%.

PMID- 21071117
TI  - Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic
      carcinoma.
AB  - Patients with adenoid cystic carcinoma of the salivary glands show over
      expression of KIT in a high proportion of cases. Options for systemic treatment
      are limited in locally advanced and metastatic disease. We explored the efficacy
      of imatinib and cisplatin combined in this group of patients. A Gehan's two
      stage, phase II trial was conducted on 28 patients. Those with progressive,
      locally advanced, and metastatic disease with an over-expression of KIT were
      treated with single agent imatinib 800 mg daily for two months, followed by a
      combination of imatinib 400mg daily and cisplatin 80 mg/m(2) at four-weekly
      intervals for six cycles. This was followed by maintenance single agent imatinib
      400mg daily until the disease progressed. Response was monitored using
      fluorodeoxyglucose positron emission tomography (FDG-PET) and morphological
      imaging using computed tomography, magnetic resonance, and chest radiographs
      (CT/MRI/CXR). Morphological imaging showed partial response in three of 28
      patients, and five patients showed a response on FDG-PET. In addition, 19
      patients had useful stabilisation of disease. The median time to progression and
      overall survival was 15 months (range 1-43) and 35 months (range 1-75),
      respectively. The combination of imatinib and cisplatin was reasonably well
      tolerated. This combination may provide stabilisation in locally advanced and
      metastatic adenoid cystic carcinoma of the salivary glands.

PMID- 21071118
TI  - Correlation of mandibular bone quality with neurosensory disturbance after
      sagittal split ramus osteotomy.
AB  - Our aim was to find out whether the quality of bone around the inferior alveolar
      nerve is correlated with neurosensory disturbance to the nerve after sagittal
      split ramus osteotomy (SSRO) in patients with mandibular prognathism. Computed
      tomograms (CT) were taken of 35 patients with mandibular prognathism and 35
      without. To assess the density of bone around the inferior alveolar nerve, the
      width of the buccal cortical bone in the mandibular second molar regions was
      measured on CT. The Hounsfield units (HU) in the same regions were also measured.
      The number of HU in the mandible around the second molar regions was
      significantly higher (p<0.01) in those with neurosensory disturbance (p<0.01).
      The quality of bone measured by HU is associated with an increased risk of
      neurosensory disturbance, but the width of buccal bone is not.

PMID- 21071119
TI  - Effects of physiotherapy treatment on knee osteoarthritis gait data using
      principal component analysis.
AB  - BACKGROUND: Interpreting gait data is challenging due to intersubject variability
      observed in the gait pattern of both normal and pathological populations. The
      objective of this study was to investigate the impact of using principal
      component analysis for grouping knee osteoarthritis (OA) patients' gait data in
      more homogeneous groups when studying the effect of a physiotherapy treatment.
      METHODS: Three-dimensional (3D) knee kinematic and kinetic data were recorded
      during the gait of 29 participants diagnosed with knee OA before and after they
      received 12 weeks of physiotherapy treatment. Principal component analysis was
      applied to extract groups of knee flexion/extension, adduction/abduction and
      internal/external rotation angle and moment data. The treatment's effect on
      parameters of interest was assessed using paired t-tests performed before and
      after grouping the knee kinematic data. FINDINGS: Increased quadriceps and
      hamstring strength was observed following treatment (P<0.05). Except for the knee
      flexion/extension angle, two different groups (G(1) and G(2)) were extracted from
      the angle and moment data. When pre- and post-treatment analyses were performed
      considering the groups, participants exhibiting a G(2) knee moment pattern
      demonstrated a greater first peak flexion moment, lower adduction moment impulse
      and smaller rotation angle range post-treatment (P<0.05). When pre- and post
      treatment comparisons were performed without grouping, the data showed no
      treatment effect. INTERPRETATION: The results of the present study suggest that
      the effect of physiotherapy on gait mechanics of knee osteoarthritis patients may
      be masked or underestimated if kinematic data are not separated into more
      homogeneous groups when performing pre- and post-treatment comparisons.

PMID- 21071120
TI  - Nutrient stoichiometry in Sphagnum along a nitrogen deposition gradient in highly
      polluted region of Central-East Europe.
AB  - We investigated the variation of N:P and N:K ratio in ombrotrophic Sphagnum
      plants along a gradient of atmospheric N deposition from 1 to 2.5 g m(-2) year(
      1) in Central-East Europe. The N:P and N:K ratio in Sphagnum capitula increased
      significantly along the N deposition gradient. Sphagnum species from the
      Cuspidata section were characterised by significantly lower ratios at low N
      deposition. When we compared the observed N:P ratios in Sphagnum plants with the
      values reported in a previous European-wide study, we found a correspondence in
      nutrient stoichiometry only for a few bogs: higher P concentration in Sphagnum
      capitula caused a lower N:P ratio in most of the study bogs so that Sphagnum
      plants still seem N-limited despite their N saturation. Interaction between
      summer water table decrease and aerial liming of surrounding forests is proposed
      as an explanation for this discrepancy. Local forestry practice interacting with
      climate thus alter N:P stoichiometry of Sphagnum along the N deposition gradient.

PMID- 21071121
TI  - Effects of compositional heterogeneity and nanoporosity of raw and treated
      biomass-generated soot on adsorption and absorption of organic contaminants.
AB  - A biomass-generated soot was sequentially treated by HCl-HF solution, organic
      solvent, and oxidative acid to remove ash, extractable native organic matter
      (EOM), and amorphous carbon. The compositional heterogeneity and nano-structure
      of the untreated and treated soot samples were characterized by elemental
      analysis, thermal gravimetric analysis, BET-N(2) surface area, and electron
      microscopic analysis. Sorption properties of polar and nonpolar organic
      pollutants onto the soot samples were compared, and individual contributions of
      adsorption and absorption were quantified. The sorption isotherms for raw sample
      were practically linear, while were nonlinear for the pretreated-soot. The
      removal of EOM enhanced adsorption and reduced absorption, indicating that EOM
      served as a partitioning phase and simultaneously masked the adsorptive sites. By
      drastic-oxidation, the outer amorphous carbon and the inner disordered core of
      the soot particles were completely removed, and a fullerene-like nanoporous
      structure (aromatic shell) was created, which promoted additional pi-pi
      interaction between phenanthrene and the soot.

PMID- 21071122
TI  - Adaptation, validation and application of the chemo-thermal oxidation method to
      quantify black carbon in soils.
AB  - The chemo-thermal oxidation method at 375 degrees C (CTO-375) has been widely
      used to quantify black carbon (BC) in sediments. In the present study, CTO-375
      was tested and adapted for application to soil, accounting for some matrix
      specific properties like high organic carbon (<= 39%) and carbonate (<= 37%)
      content. Average recoveries of standard reference material SRM-2975 ranged from
      25 to 86% for nine representative Swiss and Indian samples, which is similar to
      literature data for sediments. The adapted method was applied to selected samples
      of the Swiss soil monitoring network (NABO). BC content exhibited different
      patterns in three soil profiles while contribution of BC to TOC was found maximum
      below the topsoil at all three sites, however at different depths (60-130 cm).
      Six different NABO sites exhibited largely constant BC concentrations over the
      last 25 years, with short-term (6 months) prevailing over long-term (5 years)
      temporal fluctuations.

PMID- 21071123
TI  - Free atmospheric phosphine concentrations and fluxes in different wetland
      ecosystems, China.
AB  - Atmospheric phosphine (PH(3)) fluxes from typical types of wetlands and PH(3)
      concentrations in adjacent atmospheric air were measured. The seasonal
      distribution of PH(3) in marsh and paddy fields were observed. Positive PH(3)
      fluxes are significantly related to high air temperature (summer season) and
      increased vegetation. It is concluded that vegetation speeds up the liberation of
      PH(3) from soils, while water coverage might function as a diffusion barrier from
      soils or sediments to the atmosphere. The concentrations of atmospheric PH(3) (ng
      m(-3)) above different wetlands decrease in the order of paddy fields (51.8 +/-
      3.1) > marsh (46.5 +/- 20.5) > lake (37.0 +/- 22.7) > coastal wetland (1.71 +/-
      0.73). Highest atmospheric PH(3) levels in marsh are found in summer. In paddy
      fields, atmospheric PH(3) concentrations in flourishing stages are higher than
      those in slowly growing stages.

PMID- 21071124
TI  - A second life for old data: global patterns in pollution ecology revealed from
      published observational studies.
AB  - A synthesis of research on the responses of terrestrial biota (1095 effect sizes)
      to industrial pollution (206 point emission sources) was conducted to reveal
      regional and global patterns from small-scale observational studies. A meta
      analysis, in combination with other statistical methods, showed that the effects
      of pollution depend on characteristics of the specific polluter (type, amount of
      emission, duration of impact on biota), the affected organism (trophic group,
      life history), the level at which the response was measured (organism,
      population, community), and the environment (biome, climate). In spite of high
      heterogeneity in responses, we have detected several general patterns. We suggest
      that the development of evolutionary adaptations to pollution is a common
      phenomenon and that the harmful effects of pollution on terrestrial ecosystems
      are likely to increase as the climate warms. We argue that community- and
      ecosystem-level responses to pollution should be explored directly, rather than
      deduced from organism-level studies.

PMID- 21071125
TI  - Effects of nitrogen deposition and soil fertility on cover and physiology of
      Cladonia foliacea (Huds.) Willd., a lichen of biological soil crusts from
      Mediterranean Spain.
AB  - We are fertilizing a thicket with 0, 10, 20 and 50 kg nitrogen (N) ha(-1) yr(-1)
      in central Spain. Here we report changes in cover, pigments, pigment ratios and
      FvFm of the N-tolerant, terricolous, lichen Cladonia foliacea after 1-2 y adding
      N in order to study its potential as biomarker of atmospheric pollution. Cover
      tended to increase. Pigments increased with fertilization independently of the
      dose supplied but only significantly with soil nitrate as covariate. beta
      carotene/chlorophylls increased with 20-50 kg N ha(-1) yr(-1) (over the
      background) and neoxanthin/chlorophylls also increased with N.
      (Neoxanthin+lutein)/carotene decreased with N when nitrate and pH seasonalities
      were used as covariates. Between 26 and 56 kg N ha(-1) yr(-1).Pinho et al. (2012)
      suggested that the critical Nload for Mediterranean epiphytic lichens (based on
      responses of functional groups) was lower than 26 kg N ha(-1) yr(-1) [corrected].
      Water-stress, iron and copper also explained variables of lichen physiology. We
      conclude that this tolerant lichen could be used as biomarker and that responses
      to N are complex in heterogeneous Mediterranean-type landscapes.

PMID- 21071126
TI  - Entitlements to health care: why is there a preference for private facilities
      among poorer residents of Chennai, India?
AB  - This paper examines access to health care by poorer residents in Chennai, India.
      It reveals constraining and enabling conditions for impoverished users seeking
      treatment. We explore patterns of health-seeking behaviour through the reasoning
      of residents themselves as well as stakeholders involved in providing care for
      these users. Particular attention is paid to the needy residents' preference for
      private health care providers despite the costs involved and that free public
      facilities are available. We address this issue by combining Sen's entitlement
      approach with Penchansky and Thomas' work on access to health care. Based on data
      gathered in a qualitative field-based research design including interviews with
      14 residents and 58 stakeholders involved in caring for poor people, we argue
      that the availability of health care facilities within walking distance is a
      necessary but not sufficient precondition for satisfactory access. Rather, we
      demonstrate the influence of 'entitlements to health care' which allow poor
      households that are endowed with resources such as income, knowledge and social
      networks to realise access. The narratives we present reveal not only experiences
      of health care, but also feelings about its utilisation. The latter, we contend,
      are crucial in determining choice of health care facilities. This finding
      suggests that analyses of affordability and physical access to health care in
      less developed countries should include a focus on emotional dimensions of
      utilisation. In other words, there is a need to consider not only effective
      access to health care, but also affective dimensions of treatment for poorer
      citizens.

PMID- 21071127
TI  - Medical training as adventure-wonder and adventure-ordeal: a dialogical analysis
      of affect-laden pedagogy.
AB  - Our purpose is to examine the possibilities of Bakhtinian dialogical analysis for
      understanding students' experiences of medical training. Twenty-three interviews
      were conducted with eleven British medical students intercalating in psychology.
      Forty emotionally resonant key moments were identified for analysis. Our analysis
      illustrates students' use of the professional genre to present their training as
      emotionally neutral. However, we show how medical training can be framed in more
      unofficial and affective-laden ways in which threshold moments of crisis are
      presented as space-time breaches characteristic of the genres of adventure-wonder
      and adventure-ordeal. This affect was often depotentiated in the narratives
      through brief allusion to the professional genre. This cycling between genres
      suggests that the students were searching for an appropriate way in which to
      frame their experiences, a central dilemma being the extent to which medical
      training makes sense within an immediate and affect-laden, or future-orientated
      and affect-neutral, pedagogy. Finally, we identify how consultants are an
      important aspect of the affective experience of medical training who, at their
      best, offer inspiring exemplars of flexible movement between official and
      unofficial ways of being a doctor. In conclusion, we demonstrate the potential of
      genres to make sense, and to organize the experience, of medical training
      spatially in terms of moving between personal and impersonal contact, temporally
      in terms of moving between the extraordinary and routine, and affectively in
      terms of moving between potent and neutral affect. Learning to use the
      professional genre is part of enculturation as a doctor and can be helpful in
      providing a framework restoring coherence and composure through engaging with,
      and reformulating, difficult experiences. However, it is important to take
      seriously the resistance many of the students demonstrated to the professional
      genre as a possible barometer of its acceptability to the general public.

PMID- 21071128
TI  - Economic fluctuations and suicide: a comparison of Taiwan and Hong Kong.
AB  - This study examines the impact of unemployment on suicide rates in Taiwan and
      Hong Kong during the period of rising unemployment (1997-2003) and its subsequent
      decline (2003-2007), with 2003 as the turning point. During these initial years
      of high unemployment, suicide rates increased markedly in Hong Kong and Taiwan;
      however, as employment conditions improved, suicide rates fell in Hong Kong but
      continued to increase in Taiwan. ARMAX time-series models with appropriate time
      lags were used to assess the impact of unemployment on suicide rates for both
      periods. It was found that for Taiwan, the unemployment rate was positively
      related with the suicide rate for both males and females during the period of
      high unemployment, whereas a negative relationship was observed as the rate of
      unemployment decreased. On the other hand, the reduction in suicide rates since
      2003 was not statistically significantly related to the improvement of employment
      conditions for Hong Kong; whereas the suicide rate in Taiwan still remained at a
      high level due to the increasing number of charcoal burning suicide deaths
      despite improvements in employment conditions. In conclusion, lower unemployment
      was not necessarily associated with lower suicide rates. Exogenous factors other
      than economic ones have been suggested to be important for understanding
      differences in suicide patterns in Hong Kong and Taiwan. The impact of employment
      conditions on suicide across different countries deserves further investigation.

PMID- 21071129
TI  - Fresh or frozen? Classifying 'spare' embryos for donation to human embryonic stem
      cell research.
AB  - United Kingdom (UK) funding to build human embryonic stem cell (hESC) derivation
      labs within assisted conception units (ACU) was intended to facilitate the 'In
      vitro fertilisation (IVF)-stem cell interface', including the flow of fresh
      'spare' embryos to stem cell labs. However, in the three sites reported on here,
      which received this funding, most of the embryos used for hESC research came from
      long term cryopreservation storage and/or outside clinics. In this paper we
      explore some of the clinical, technical, social and ethical factors that might
      help to explain this situation. We report from our qualitative study of the
      ethical frameworks for approaching women/couples for donation of embryos to stem
      cell research. Members of staff took part in 44 interviews and six ethics
      discussion groups held at our study sites between February 2008 and October 2009.
      We focus here on their articulations of social and ethical, as well as
      scientific, dimensions in the contingent classification of 'spare' embryos,
      entailing uncertainty, fluidity and naturalisation in classifying work. Social
      and ethical factors include acknowledging and responding to uncertainty in
      classifying embryos; retaining 'fluidity' in the grading system to give embryos
      'every chance'; tensions between standardisation and variation in enacting a
      'fair' grading system; enhancement of patient choice and control, and prevention
      of regret; and incorporation of patients' values in construction of ethically
      acceptable embryo 'spareness' ('frozen' embryos, and embryos determined through
      preimplantation genetic diagnosis (PGD) to be genetically 'affected'). We argue
      that the success of the 'built moral environment' of ACU with adjoining stem cell
      laboratories building projects intended to facilitate the 'IVF-stem cell
      interface' may depend not only on architecture, but also on the part such social
      and ethical factors play in configuration of embryos as particular kinds of moral
      work objects.

PMID- 21071130
TI  - [The clinical view through the Archives: the clinical notes of 2009].
AB  - The Clinical Notes published in 2009 serve as a resource to reflect on clinical
      aspects relevant to different clinical entities. Through this review an attempt
      is likewise made to bring the reader closer to the clinical reality of our
      environment.

PMID- 21071131
TI  - S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation
      from cardiac arrest with hypothermia treatment.
AB  - OBJECTIVE: To conduct a pilot study to evaluate the blood levels of brain derived
      neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron
      specific enolase (NSE) and S-100B as prognostic markers for neurological outcome
      6 months after hypothermia treatment following resuscitation from cardiac arrest.
      DESIGN: Prospective observational study. SETTING: One intensive care unit at
      Uppsala University Hospital. PATIENTS: Thirty-one unconscious patients
      resuscitated after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Unconscious patients after cardiac arrest with restoration of
      spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34
      degrees C for 26h. Time from cardiac arrest to target temperature was measured.
      Blood samples were collected at intervals of 1-108h after ROSC. Neurological
      outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC)
      scale at discharge from intensive care and again 6 months later, when 15/31
      patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the
      predictive biomarkers, S-100B at 24h after ROSC was the best, predicting poor
      outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96h
      after ROSC predicted poor outcome, with sensitivity of 57% and specificity of
      93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest
      to target temperature was shorter for those with poor outcome. CONCLUSIONS: The
      blood concentration of S-100B at 24h after ROSC is highly predictive of outcome
      in patients treated with mild hypothermia after cardiac arrest.

PMID- 21071132
TI  - Recycling of ash from biomass incinerator in clay matrix to produce ceramic
      bricks.
AB  - The objective of this study is to investigate the effect of incorporation of ash
      from biomass incinerator as raw material on the production of ceramic bricks for
      their application in construction. So, for the fabrication of bricks,
      compositions were prepared with addition of increasing amounts of waste ash (0%,
      10%, 20%, 30%, 40% and 50% in wt.) in the clay body. The mixed samples were
      sintered using conventional powder processing based on powder compaction at 54.5
      MPa and firing them at 950  degrees C without the addition of additives. Effect
      on apparent density, water absorption and mechanical properties were
      investigated. The results showed that water absorption increased and apparent
      density and compressive strength decreased with higher amounts of ash. Bricks
      with an ash content up to 20% meet the UNE standards compressive strength. As a
      result, since interesting performances were observed, the potential use of ashes
      from biomass incinerator up to 20 wt.% in ceramic formulations of industrial
      interest was confirmed. In this sense, incorporating ashes into clay body reduces
      environmental problems and total cost of raw material disposition.

PMID- 21071133
TI  - DNA-based diagnostic tests for Salmonella strains targeting hilA, agfA, spvC and
      sef genes.
AB  - The goal of this study was to evaluate the suitability of the hilA, agfA, spvC
      and sef genes amplification by PCR as a method for detection of Salmonella
      strains. Twenty nine isolates of Salmonella spp. including 6 different serotypes
      were analyzed in this study. The bacteria were isolated between 2005 and 2007 and
      serotyped at the Clinical Hospital of Infectious Disease, Cluj-Napoca. Ten non
      Salmonella strains were also tested by the same procedure. We used a direct PCR
      technique, DNA extraction had been skipped and the bacterial cell wall
      denaturated in the first step of the reaction. All Salmonella strains gave
      positive results by the PCR amplification of hilA gene. The utilization of the
      sef, and spvC genes or spvC and agfA genes in a multiplex PCR provides a valuable
      diagnostic tool for Salmonella enteritidis strains.

PMID- 21071134
TI  - Metal and oxalate contamination in a suburban watershed in the greater Toronto
      area: the benefits of combining acid leach and selective extraction procedures.
AB  - Environmentally available concentrations of Fe, Mn, Zn, Cu, Pb, Cr and Ni in
      soils and sediments from a small suburban catchment, obtained using an acid leach
      procedure, are compared to the Ontario Ministry of the Environment lowest effect
      level (LEL) and severe effect levels (SEL) and to Provincial sediment quality
      guidelines (PSQG's). These data are then compared to the bioavailability,
      potential bioavailability and non-bioavailability of the same metals, plus
      oxalate concentration, identified using a selective extraction procedure. This
      combination of techniques enhanced analytical interpretation with respect to
      metal mobility and potential metal contamination. Selective extraction
      highlighted the presence of oxalate as a potential contaminant, especially in
      poorly drained valley floor deposits (33,633 mg kg(-1) and 26,284 mg kg(-1)) and
      lakeshore sediments (27,095 mg kg(-1) and 13,729 mg kg(-1)). These levels are
      considerably in excess of those previously documented in a similar study from Rio
      de Janeiro, where contamination of urban sediment by sewage is a recognised
      environmental problem, and could possibly be used both as an indicator of similar
      contamination and the identification of those areas that warrant further
      investigation.

PMID- 21071135
TI  - Doc, what are my chances? A conversation about prognostic uncertainty.

PMID- 21071136
TI  - Targeting c-FLIP in cancer.
AB  - Cellular-FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that
      inhibits cell death mediated by the death receptors Fas, DR4, DR5, and TNF-R1.
      Three splice variants of c-FLIP function at the DISC level by blocking the
      processing and activation of procaspase-8 and -10. Overexpression of c-FLIP has
      been identified in many different tumour types, and its downregulation in vitro
      has been shown to restore apoptosis mediated by CD95L and TRAIL. c-FLIP therefore
      represents a promising target for cancer therapy. This review focuses on the
      molecular mechanisms that control c-FLIP expression and current research into
      inhibitors of the protein. Increasing evidence supports the investigation of c
      FLIP as a therapeutic target to restore an apoptotic response in cancer cells.

PMID- 21071137
TI  - p53-Dependent repression of focal adhesion kinase in response to estradiol in
      breast cancer cell-lines.
AB  - Mutations in the TP53 suppressor gene are frequent in breast cancers. These
      mutations are associated with poor prognosis, thought to be due to proliferative
      advantage and poor response to chemotherapy associated with loss of p53 function.
      The focal adhesion kinase (FAK/PTK2), a tyrosine kinase, is over-expressed in a
      variety of human tumors including breast cancers. FAK is a critical regulator of
      adhesion and motility and its over-expression is associated with increased
      metastatic potential. Recently, FAK promoter has been shown to contain p53
      responsive elements and to be down-regulated by DNA-damage in a p53-dependent
      manner. Here, we have used five estrogen-dependent breast cancer cells lines with
      different p53 status, including an isogenic model, to show that FAK expression
      was regulated in a p53-dependent manner in response to estradiol. FAK protein and
      mRNA expression were down-regulated by estradiol in wild-type but not mutant p53
      cells. Moreover, silencing wild-type p53 increased FAK expression, while over
      expressing p53 repressed FAK expression. ChIP experiment showed that p53 bound to
      FAK promoter in the presence of estradiol in p53 wild-type but not in mutant p53
      cells, suggesting a direct role of p53 in down regulating FAK mRNA expression.
      FAK mRNA expression was also found to correlate with TP53 mutation status in a
      series of breast tumors. Finally, loss of FAK down-regulation in p53 mutant cells
      was correlated with increased proliferation and invasion upon estradiol
      stimulation, while FAK silencing reduced invasion. These results suggest that p53
      is an important down regulator of FAK and that loss of p53 function in breast
      cancer may contribute to the metastatic potential of estrogen-responsive tumors
      through uncontrolled FAK expression upon estrogens stimulation.

PMID- 21071138
TI  - Degradation of trichloroethylene by Fenton reaction in pyrite suspension.
AB  - Degradation of trichloroethylene (TCE) by Fenton reaction in pyrite suspension
      was investigated in a closed batch system under various experimental conditions.
      TCE was oxidatively degraded by OH in the pyrite Fenton system and its
      degradation kinetics was significantly enhanced by the catalysis of pyrite to
      form OH by decomposing H(2)O(2). In contrast to an ordinary classic Fenton
      reaction showing a second-order kinetics, the oxidative degradation of TCE by the
      pyrite Fenton reaction was properly fitted by a pseudo-first-order rate law.
      Degradation kinetics of TCE in the pyrite Fenton reaction was significantly
      influenced by concentrations of pyrite and H(2)O(2) and initial suspension pH.
      Kinetic rate constant of TCE increased proportionally (0.0030 +/- 0.0001-0.1910
      +/- 0.0078 min(-1)) as the pyrite concentration increased 0.21-12.82 g/L. TCE
      removal was more than 97%, once H(2)O(2) addition exceeded 125 mM at initial pH
      3. The kinetic rate constant also increased (0.0160 +/- 0.005-0.0516 +/- 0.0029
      min(-1)) as H(2)O(2) concentration increased 21-251 mM, however its increase
      showed a saturation pattern. The kinetic rate constant decreased (0.0516 +/-
      0.0029-0.0079 +/- 0.0021 min(-1)) as initial suspension pH increased 3-11. We did
      not observe any significant effect of TCE concentration on the degradation
      kinetics of TCE in the pyrite Fenton reaction as TCE concentration increased.

PMID- 21071139
TI  - Preparation of a novel inorganic polymer coagulant from oil shale ash.
AB  - In this paper, a novel inorganic polymer coagulant was prepared from oil shale
      ash, and was adopted to treat municipal sewage. Effect of coagulants dosage on
      the turbidity and Chemical Oxygen Demand (COD) removal were examined. In
      addition, the structure and morphology of the prepared coagulants were
      characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD)
      and infra-red spectra (FTIR), furthermore, the zeta potential of the sewage and
      the microscopic images of flocks were measured. The results indicate that the
      characterization and coagulation performance of the samples are affected by Al/Fe
      mole ratios and the type of lixiviant. The most of Fe(3+) is not turned into the
      crystals, which means that the samples are not simple mixtures of raw materials
      but inorganic polymer compounds with iron, aluminum, silicon and other ions. When
      Al/Fe mole ratio is 0.71 or the 2HCl/H(2)SO(4) mole ratio of the lixiviant is
      1:1, the coagulation performance of the sample is better than that of the others.
      The integrated analysis suggests that the entrapment, adsorption and complexation
      abilities play important roles in coagulation process although the charge
      neutralization is weak. Also, the chain-net structure and the suitable size of
      polymer group are favorable for the entrapment, adsorption and complexation
      ability of the samples.

PMID- 21071140
TI  - Long-term analysis of clogging and oil bio-degradation in a System of Catchment,
      Pre-treatment and Treatment (SCPT).
AB  - Runoff contamination has motivated the development of different systems for its
      treatment in order to decrease the pollutant load that is discharged into natural
      water bodies. In the long term, these systems may undergo operational problems.
      This paper presents the results obtained in a laboratory study with a 1:1 scale
      prototype of a System of Catchment, Pre-treatment and Treatment (SCPT) of runoff
      waters. The analysis aims to establish the operational behaviour of the SCPT in
      the long term with respect to oil degradation and hydraulic conductivity in the
      geotextile filter. It is concluded that bio-degradation processes take place
      inside the SCPT and that hydraulic conductivity of the geotextile filtration
      system decreases slowly with successive simulated runoff events.

PMID- 21071141
TI  - Investigation on Cu(II) adsorption on cobalt silicate precipitation tube (CSPT)
      in aqueous medium.
AB  - Cu(II) adsorption on cobalt silicate precipitation tube (CSPT) in aqueous medium
      has been reported. These tubes are porous with negative surface sites having
      isoelectric point (IEP) at pH 4.4. Cu(II) adsorption data follow Langmuir
      isotherm. CSPT has high Cu(II) loading capacity, which is a function of both
      Cu(II) concentration and CSPT weight. Adsorption bond energy obtained from
      Langmuir isotherm suggests a physisorption process. The adsorption process is
      endothermic and spontaneous. Adsorption kinetics follows pseudo second order
      model with activation energy (15.4 kJ mol(-1)) typical for physisorption process.

PMID- 21071142
TI  - Micellar-enhanced ultrafiltration of cadmium and methylene blue in synthetic
      wastewater using SDS.
AB  - Single and simultaneous removal of Cd(2+) and methylene blue (MB) with sodium
      dodecyl sulfate (SDS) by micellar-enhanced ultrafiltration under different
      experimental conditions was investigated. In single removal process, with initial
      SDS concentration increasing, the removal efficiency of Cd(2+) and MB kept
      increasing and then decreased. When the initial concentrations of SDS and Cd(2+)
      were 1.0 cmc and 50 mg L(-1), respectively, the maximum removal efficiency of
      Cd(2+) was obtained as 99.2%. Removal efficiency of MB could achieve more than
      99.9% with initial SDS concentration below 2.0 cmc. As compared with single
      Cd(2+) removal, the removal efficiency of Cd(2+) in the presence of MB was
      slightly higher with initial SDS concentration below 1.0 cmc, while decreased
      with the SDS concentration above 1.0 cmc. The maximum removal efficiency of
      Cd(2+) was 98.8% when initial concentrations of SDS and MB were 1.0 cmc and 4 mg
      L(-1), respectively. The removal efficiency of MB in the presence of Cd(2+) could
      achieve higher than 96.5%, which was only 3.4% less than the optimum result of
      the single removal. Meanwhile, effect of pH on removal efficiency of Cd(2+) was
      more significant than that of MB.

PMID- 21071143
TI  - Sorption of SO(2) and NO from simulated flue gas over rice husk ash
      (RHA)/CaO/CeO(2) sorbent: evaluation of deactivation kinetic parameters.
AB  - In this study, the kinetic parameters of rice husk ash (RHA)/CaO/CeO(2) sorbent
      for SO(2) and NO sorptions were investigated in a laboratory-scale stainless
      steel fixed-bed reactor. Data experiments were obtained from our previous results
      and additional independent experiments were carried out at different conditions.
      The initial sorption rate constant (k(0)) and deactivation rate constant (k(d))
      for SO(2)/NO sorptions were obtained from the nonlinear regression analysis of
      the experimental breakthrough data using deactivation kinetic model. Both the
      initial sorption rate constants and deactivation rate constants increased with
      increasing temperature, except at operating temperature of 170  degrees C. The
      activation energy and frequency factor for the SO(2) sorption were found to be
      18.0 kJ/mol and 7.37 * 10(5)cm(3)/(g min), respectively. Whereas the activation
      energy and frequency factor for the NO sorption, were estimated to be 5.64 kJ/mol
      and 2.19 * 10(4)cm(3)/(g min), respectively. The deactivation kinetic model was
      found to give a very good agreement with the experimental data of the SO(2)/NO
      sorptions.

PMID- 21071144
TI  - Recovery of iron from vanadium tailings with coal-based direct reduction followed
      by magnetic separation.
AB  - A technique with coal-based direct reduction followed by magnetic separation is
      presented in this study for recovering and reusing iron otherwise wasted in
      vanadium tailings. Process parameters such as usage of additives,
      tailings/reductant/additives ratio, reduction temperature and time, as well as
      particle size were experimentally determined. The optimum process parameters were
      proposed as follows: using lime as the additive, lignite as the reductant, weight
      ratios of vanadium tailings/lignite/lime at 100:30:10, reduction roasting at 1200
      degrees C for 60 min, and particle size of 98% less than 30 MUm in the final
      roasted product feeding to magnetic separation. Under these conditions, a
      magnetic concentrate containing 90.31% total iron and 89.76% metallization iron
      with a total iron recovery rate of 83.88% was obtained. In addition,
      mineralography of vanadium tailings, coal-based reduction product and magnetic
      concentrate were studied by X-ray powder diffraction technique (XRD). The
      microstructures of above products were analyzed by scanning electron microscope
      (SEM) to help understand the mechanism.

PMID- 21071145
TI  - Novel chelating resin with cyanoguanidine group: useful recyclable materials for
      Hg(II) removal in aqueous environment.
AB  - A novel chelating resin containing cyanoguanidine moiety has been successfully
      prepared by the functionalizing reaction of a macroporous bead based on
      chloromethylated copolymer of styrene-divinylbenzene (CMPS) with dicyandiamide
      (DCDA) in the presence of phase transfer catalyst. The Fourier transform-infrared
      spectra (FT-IR) and scanning electron microscopy (SEM) were employed in the
      characterization of the resulting chelating resin, meanwhile, the adsorption
      properties of the resin for Hg(II) were investigated by batch and column methods.
      The results indicated that the resin displayed a marked advantage in Hg(II)
      binding capacity, and the saturated adsorption capacity estimated from the
      Langmuir model was dramatically up to 1077 mg g(-1) at 45  degrees C.
      Furthermore, it was found that the resin was able to selectively separate Hg(II)
      from multicomponent solutions with Zn(II), Cu(II), Pb(II) and Mg(II). The
      desorption process of Hg(II) was tested with different eluents and the ratio of
      the highest recovery reached to 96% under eluting condition of 1M HCl+10%
      thiourea. Consequently, the resulting chelating resin would provide a potential
      application for treatment process of Hg(II) containing wastewater.

PMID- 21071146
TI  - Adsorption of o-, m- and p-nitrophenols onto organically modified bentonites.
AB  - Experiments were conducted on the adsorption characteristics of o-, m- and p
      nitrophenols by organically modified bentonites at different temperatures. Two
      organobentonites (HDTMA-B and PEG-B) were synthesized using
      hexadecyltrimethylammonium bromide (HDTMABr) and poly(ethylene glycol) butyl
      ether (PEG). Synthesized HDTMA-B and PEG-B were characterized by XRD, FTIR and
      DTA-TG analyses and their specific surface area, particle size and pore size
      distributions were determined. BET surface areas and basal spacings (d(001)) of
      the HDTMA-B and PEG-B were found to be 38.71 m(2)g(-1), 69.04 m(2)g(-1) and 21.96
      A, 15.17 A, respectively. Increased adsorption with temperature indicates that
      the process is endothermic for o-nitrophenol. On the other hand m- and p
      nitrophenols exhibited lower rates of adsorption at higher temperatures
      suggesting a regular exothermic process taking place. Results were analyzed
      according to the Langmuir, Freundlich and Dubinin-Redushkevich (D-R) isotherm
      equations using linearized correlation coefficient at different temperatures.
      R(L) separation factors for Langmuir and the n values for Freundlich isotherms
      showed that m- and p-nitrophenols are favorably adsorbed by HDTMA-B and, p
      nitrophenol is favored by PEG-B. Adsorption of o-, m- and p-nitrophenols as
      single components or from their binary mixtures on HDTMA-B and, p-nitrophenol on
      PEG-B are all defined to be physical in nature.

PMID- 21071147
TI  - Allopregnanolone prevents and suppresses oxaliplatin-evoked painful neuropathy:
      multi-parametric assessment and direct evidence.
AB  - Oxaliplatin (OXAL) is a platinum-based drug used for the treatment of colorectal,
      lung, breast and ovarian cancers. OXAL does not cause renal or hematologic
      toxicity. However, OXAL induces neuropathic pain which hampers the chemotherapy
      success. Attempts with neuroprotective agents including anticonvulsivants and
      antidepressants were made to prevent OXAL-induced painful neuropathy but the
      clinical data are controversial and the tested neuroprotectors are able to evoke
      themselves undesirable effects. Here, we demonstrated that the natural
      neurosteroid allopregnanolone (3alpha,5alpha-THP), known to be devoid of toxic
      side-effects in humans and experimental models, prevented and suppressed OXAL
      induced painful neuropathic symptoms. Indeed, 3alpha,5alpha-THP repaired OXAL
      evoked neurochemical and functional alterations in peripheral nerves and intra
      epidermal nerve fibers (IENF). Behavioral analyses showed that prophylactic or
      corrective 3alpha,5alpha-THP treatment (4mg/kg/2days) respectively prevented or
      abolished OXAL-induced cold allodynia, mechanical allodynia and hyperalgesia by
      reversing to normal decreased thermal and mechanical pain thresholds of OXAL
      treated rats. Electrophysiological investigations revealed that 3alpha,5alpha-THP
      restored control values of sciatic nerve conduction velocity and action potential
      peak amplitude drastically reduced by OXAL-treatment. Furthermore,
      immunohistochemistry and confocal microscopic quantifications demonstrated that
      3alpha,5alpha-THP repaired OXAL-induced neurochemical/cellular alterations by
      restoring IENF control density and normal level of neurofilament 200kDa that was
      strongly repressed by OXAL in dorsal root ganglion neurons and sciatic nerve
      axons. OXAL showed no toxicity for the non-compact myelin protein 2',3'-cyclic
      nucleotide-3'-phosphodiesterase whose expression level was similarly increased by
      3alpha,5alpha-THP in controls and OXAL-treated rat nerves. Together, these
      results may be interesting for the development of natural or safe neurosteroid
      based neuroprotective strategy against anticancer drug-evoked painful neuropathy.

PMID- 21071148
TI  - Infections with gastrointestinal nematodes, Fasciola and Paramphistomum in cattle
      in Cambodia and their association with morbidity parameters.
AB  - Prevalence and seasonal variations of helminth infections and their association
      with morbidity parameters were studied in traditionally reared Cambodian cattle.
      Four villages in two provinces of West Cambodia were visited on monthly intervals
      over a period of 11 months, during which 2391 animals were faecal and blood
      sampled for parasitological and haematological examinations. The body condition
      score (BCS), faecal consistency (diarrhoea score, DS), colour of the ocular
      conjunctivae (FAMACHA((c))) and packed cell volume were determined for each
      individual animal. The overall proportion of samples that was positive for
      gastrointestinal nematodes was 52%, 44% and 37% in calves (from 1 to 6 months),
      young animals (6 to 24 months) and adults (over 24 months), respectively, while
      geometric mean faecal egg counts (FECs) for each of these age categories were
      125, 66 and 15 eggs per gram, respectively. Six genera of strongyles were found
      in the faecal cultures, i.e. in descending order of occurrence, Cooperia,
      Oesophagostomum, Haemonchus, Trichostrongylus, Mecistocirrus and Bunostomum. The
      prevalences of Fasciola and Paramphistomum, estimated by coprological
      examination, varied between 5-20% and 45-95%, respectively. Logistic mixed models
      were used to investigate associations of morbidity markers with the presence of
      parasite infection. A low BCS was associated with gastrointestinal nematode and
      liver fluke infections, and soft faecal consistency with Paramphistomum
      infections. However, other factors such as nutritional deficiencies and
      intercurrent diseases are likely to enhance the effects of parasites and should
      therefore be considered when using these morbidity parameters as indicators of
      parasitism.

PMID- 21071149
TI  - Distribution and prevalence of Cytauxzoon felis in bobcats (Lynx rufus), the
      natural reservoir, and other wild felids in thirteen states.
AB  - Cytauxzoon felis, a protozoan parasite of wild and domestic felids, is the
      causative agent of cytauxzoonosis in domestic and some exotic felids in the
      United States. The bobcat (Lynx rufus) is the natural reservoir for this
      parasite, but other felids such as Florida panthers (Puma concolor coryii) and
      domestic cats may maintain long-term parasitemias and serve as reservoirs.
      Experimentally, two tick species, Dermacentor variabilis and Amblyomma
      americanum, have demonstrated the ability to transmit C. felis. These two tick
      species have overlapping distributions throughout much of the southeastern United
      States. The objective of the current study was to determine the distribution and
      prevalence of C. felis in free-ranging bobcat populations from 13 states
      including California, Colorado, Florida, Georgia, Kansas, Kentucky, Missouri,
      North Carolina, North Dakota, Ohio, Oklahoma, South Carolina, and West Virginia.
      These states were selected because of differential vector presence; D. variabilis
      is present in each of these states except for the region of Colorado sampled and
      A. americanum is currently known to be present only in a subset of these states.
      Blood or spleen samples from 696 bobcats were tested for C. felis infection by a
      polymerase chain reaction (PCR) assay which targeted the first ribosomal internal
      transcribed spacer region (ITS-1). Significantly higher prevalences of C. felis
      were detected from Missouri (79%, n=39), North Carolina (63%, n=8), Oklahoma
      (60%, n=20), South Carolina (57%, n=7), Kentucky (55%, n=74), Florida (44%,
      n=45), and Kansas (27%, n=41) compared with Georgia (9%, n=159), North Dakota
      (2.4%, n=124), Ohio (0%, n=19), West Virginia (0%, n=37), California (0%, n=26),
      and Colorado (0%, n=67). In addition to bobcats, seven cougars (Puma concolor)
      from Georgia, Louisiana, and North Dakota and one serval (Leptailurus serval)
      from Louisiana were tested for C. felis. Only one cougar from Louisiana was PCR
      positive, which represents the first report of an infected cougar outside of the
      Florida panther population. These data also indicate that C. felis is present in
      North Dakota where infection has not been reported in domestic cats. Based on a
      nonparametric analysis, prevalence rates were significantly higher in states
      where there are established populations of A. americanum, which supports recent
      data on the experimental transmission of C. felis by A. americanum and the fact
      that domestic cat clinical cases are temporally associated with A. americanum
      activity. Collectively, these data confirm that bobcats are a common reservoir
      for C. felis and that A. americanum is likely an epidemiologically important
      vector.

PMID- 21071150
TI  - Social influences on plasma testosterone levels in morphine withdrawn adolescent
      mice and their drug-naive cage-mates.
AB  - Opioid administration in males results in opioid-induced androgen deficiency
      which persists throughout the treatment. In adults, this quickly reverses once
      opioid administration is suspended. However, less is known about the duration of
      the effect following drug discontinuation in adolescents. Given the significant
      implications to sexual maturation in adolescent males, this study examined plasma
      testosterone levels in both morphine withdrawn mice and their drug-naive (saline
      injected) cage-mates as compared to drug-naive mice housed physically and
      visually separate from the morphine-treated mice ('saline only'). Consistent with
      the literature, plasma testosterone levels in morphine withdrawn adults were
      reduced on withdrawal day 1 (WD1) and returned to baseline levels by WD9. No
      significant effects were observed in their saline cage-mates. In the adolescents,
      no significant differences were observed on WD1 between the morphine withdrawn
      mice, their saline cage-mates, and the saline only mice - all of which had
      significantly lower plasma testosterone levels than adults. By WD9, testosterone
      levels in the saline only adolescent mice had reached adult levels. Notably,
      plasma testosterone levels were reduced in both the morphine withdrawn adolescent
      mice and their saline cage-mates, as compared to saline only mice. The effect was
      not a drug effect per se, given that reduced plasma testosterone levels were not
      observed in individually housed morphine withdrawn mice. Moreover, our results
      also suggest that these social effects are not solely explained by stress. These
      results have numerous implications to the short term and long term health of both
      adolescents requiring pain management and of adolescent drug addicts.

PMID- 21071151
TI  - Extracellular heat shock proteins (eHSP70) in exercise: Possible targets outside
      the immune system and their role for neurodegenerative disorders treatment.
AB  - The intracellular heat shock protein 70kDa (iHSP70) is a universal marker of
      stress protein whose expression is induced by different cell stressors, such as
      heat, metabolite deprivation, redox imbalances and also during physical exercise.
      The activation of the iHSP70 is sine qua non for the promotion of tissue repair,
      since the expression of this chaperone confers cytoprotection and also exerts
      anti-inflammatory effects. On the other hand, exercise also induces the
      appearance of HSP70 in the extracellular medium (eHSP70) but, so far, the eHSP70
      function has been mainly attributed to the activation of the immune system,
      seeming to perform an opposite function from the iHSP70. Since a moderate
      intensity exercise bout induces a general anti-inflammatory response even in the
      presence of an elevated eHSP70, this protein could carry out other functions
      rather than immune activation. Because exercise generates heat and metabolic
      challenges (especially on glucose metabolism) we suggests that the motoneurons, a
      very active (possibly one of the most stressed cells during exercise) and also
      very sensitive cells to heat and glucose metabolism imbalances, could be the
      major sites for the eHSP70 function. Due to the importance of the iHSP70 for
      repair and stress adaptation, this protein must be present in abundance on the
      site of stress and, because of its intrinsic inability response to stress [low
      heat shock factor 1 (HSF-1) activation] and the structure of the motoneurons
      (very long cells), the iHSP70, produced on the very far nucleus, is not
      appropriately transported through the axon to the axon terminal, were it is
      required. Then, during the exercise, the released eHSP70 can be internalized by
      the motoneurons and act as intracellular chaperons, protecting this cell against
      oxidative damage, protein denaturation and many others. Since a decreased iHSP70
      expression capacity is associated with neurodegeneration diseases (such as
      Parkinson, polyglutamine, Amyotrophic lateral sclerosis, Alzheimer's,
      Huntington's and many others), the understanding of the physiological function of
      the extracellular HSP70 could be helpful on the treatment of neurodegenerative
      and other neuronal diseases. Besides that, it could explain some of the
      beneficial effects of the pharmacological HSP70 activators and also the
      beneficial effects of the exercise among neuronal cells during neurodegenerative
      inducing diseases.

PMID- 21071152
TI  - A novel treatment strategy for type 2 diabetes: Targeting glucose variability and
      beta-cell failure.
AB  - Blood glucose control has been a main focus for the treatment of type 2 diabetes.
      However, poor control and side-effect still are urgent problems to be solved.
      According to common blood glucose variability and its extremely deleterious
      diabetic-related complications in clinical practice, it should be considered as a
      potential key target. And beta-cell failure has been approved that it can be
      reversible for early type 2 diabetes, which suggests another promising target. In
      this hypothesis, we propose a novel treatment strategy against on the two
      targets. An intelligent double-target drug delivery system is presented and
      characterized by dual-responsive functional gates for glucose sensitivity used
      controlled-release hypoglycemic agents and a sustained-release osmotic pump
      loaded drugs to repair impaired beta-cell into the repository, respectively. The
      proposition may provide a new early therapeutic strategy for type 2 diabetes in
      order to better hold blood glucose homeostasis.

PMID- 21071153
TI  - Does pancreatic ductal anatomy play a role in determining outcomes of pancreatic
      anastomoses?
AB  - Pancreatoduodenectomy (PD) is the surgical procedure performed for cancers of the
      head of the pancreas. Despite a substantial reduction in mortality rates
      following PD, morbidity remains high secondary to major post-operative
      complications. Post-operative pancreatic fistula (POPF), the commonest major
      complication following PD, results from the failure of the pancreato-enteric
      anastomosis. There appears to be a correlation between intrinsic pancreatic
      features like the texture of the gland and duct size and the outcome of the
      pancreatic anastomosis. Based on current clinical research data, we propose a new
      hypothesis called the "pancreatic ductal anatomy" concept. We hypothesize that
      morphological variations, anomalies or aberrations of the main pancreatic duct
      play a role in the outcome of the pancreatic anastomosis, irrespective of its
      type. The consequence of aberrant ductal anatomy is that certain areas of the
      remnant pancreas remain either undrained or partially drained, or have blocked
      ductules/ducts. This results in localized obstructive pancreatitis causing an
      inflammatory reaction which jeopardizes the anastomosis. We also propose two
      maneuvers which could possibly play a role in predicting potential problems and
      also planning the surgical resection and reconstruction in order to reduce the
      incidence of POPF. The first modality is the use of pre-operative magnetic
      resonance imaging (MRI) of the pancreatic duct, and the second maneuver is the
      gentle cannulation test of the pancreatic duct with a soft, narrow tube following
      transection of the pancreatic neck. These factors would alert the surgeon about
      potential ductal variations and could facilitate the surgical approach.

PMID- 21071154
TI  - Optimal tissue tension for secure laparoscopic knots.
AB  - Security and strength of a knot are main concerns of the surgeon since last 4000
      years. The advancement of endoscopic and minimally invasive surgery in last few
      decades had a significant influence on a knot tying. The most difficult methods
      of a knot tying are performed during endoscopic procedures, in which the surgeon
      execute instrumentation from outside the body without palpation of organs and
      three-dimensional vision. In addition, laparoscopic instruments due to friction
      in transmission mechanism have very poor force feedback. This results into
      difficulty in applying the appropriate grasping force to the tissue, resulting in
      slippage or damage to the tissue. Our hypothesis highlights the need of tissue
      approximation at the 'optimum tissue tension' sufficient to resist the slippage
      of suture/clip without strangulation. The purpose of suture is to maintain an
      approximation of the tissue until healing progresses to the point where
      artificial support is no longer necessary for the wound to resist normal stress.
      When the approximation is too tight, tension in tissue leads to diminished blood
      supply resulting into the necrosis. Various tissues need different blood supply
      and different tissue pressure for optimum healings. Proposed hypothesis helps to
      improve the feedback of current knot pushers or clip applicators used in
      laparoscopic surgery using optimum tissue tension. Tissue approximation at an
      optimal tissue tension translates into the secure laparoscopic knot/clip
      application resulting in prevention of wound dehiscence, anastomosis leak, and
      secondary haemorrhages.

PMID- 21071155
TI  - WITHDRAWN: Comparison of high performance liquid chromatography and liquid
      chromatography/tandem mass spectrometry methods in the quantification and
      confirmation of ochratoxin A in pig tissue.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21071156
TI  - Intramuscular fatty acid composition of lambs fed diets containing alternative
      protein sources.
AB  - Thirty male Merinizzata italiana lambs were divided into three groups after
      weaning according to live weight. The diet of the three groups differed in the
      main protein source used in the concentrate, soybean meal for treatment SBM, faba
      bean for treatment FB and peas for treatment PEA. Lambs were fed ad libitum and
      slaughtered at about 160 days of age. Meat from the PEA group had higher
      proportions of the essential fatty acids C18:2 omega-6 and C18:3 omega-3 than
      from FB and SBM lambs and consequently its derivatives, C20:4 omega-6 and C20:5
      omega-3 respectively, were higher in meat from PEA animals, compared to SBM and
      FB ones. The total n-3 fatty acids were highest in meat from PEA lambs and
      consequently PEA lambs showed a more favourable n-6/n-3 ratio. In conclusion the
      use of legume seeds such as peas in lamb diets positively affected intramuscular
      fatty acid composition.

PMID- 21071157
TI  - Serotonin (5-HT) precursor loading with 5-hydroxy-l-tryptophan (5-HTP) reduces
      locomotor activation produced by (+)-amphetamine in the rat.
AB  - BACKGROUND: Evidence suggests that increases in synaptic serotonin (5-HT) can
      reduce the stimulant properties of amphetamine-type drugs. Here we tested the
      hypothesis that administration of the 5-HT precursor 5-hydroxy-l-tryptophan (5
      HTP), along with the peripheral decarboxylase inhibitor benserazide, would
      decrease locomotor effects of (+)-amphetamine. METHODS: Drug treatments were
      administered to conscious male rats undergoing in vivo microdialysis in nucleus
      accumbens. During dialysis sampling, rats were housed in chambers equipped with
      photobeams to detect forward locomotion (i.e., ambulation) and repetitive
      movements (i.e., stereotypy). Extracellular concentrations of dopamine (DA) and 5
      HT were measured by high-pressure liquid chromatography with electrochemical
      detection. RESULTS: 5-HTP (10 & 30 mg/kg, i.p.) plus benserazide (30 mg/kg, i.p.)
      caused dose-related increases in 5-HT but failed to alter other parameters. (+)
      Amphetamine (0.3 & 1.0 mg/kg, i.p.) produced dose-related increases in DA,
      ambulation and stereotypy. Combined administration of 5-HTP and (+)-amphetamine
      evoked large elevations in extracellular DA and 5-HT, but caused significantly
      less ambulation than (+)-amphetamine alone (~50% reduction). CONCLUSIONS: Our
      results confirm that 5-HTP can decrease hyperactivity produced by (+)
      amphetamine, even in the presence of elevations in dialysate DA. The data suggest
      that 5-HTP and (+)-amphetamine may be useful to broadly enhance monoamine
      function in the clinical setting, while reducing undesirable effects of (+)
      amphetamine.

PMID- 21071158
TI  - Insulin-like growth factor-I (IGF-I) protects cultured equine Leydig cells from
      undergoing apoptosis.
AB  - Leydig cells located in the interstitial space of the testicular parenchyma
      produce testosterone which plays a critical role in the maintenance and
      restoration of spermatogenesis in many species, including horses. For normal
      spermatogenesis, maintaining Leydig cells is critical to provide an optimal and
      constant level of testosterone. Recently, an anti-apoptotic effect of IGF-I in
      testicular cells in rats has been reported, but a similar effect of IGF-I on
      equine Leydig cells remains to be elucidated. If IGF-I also protects stallion
      testicular cells from undergoing apoptosis, then IGF-I may have potential as a
      treatment regime to prevent testicular degeneration. The present study was
      designed to evaluate the anti-apoptotic effect of IGF-I on cultured equine Leydig
      cells. Testes were collected from 5 post-pubertal stallions (2-4 years old)
      during routine castrations. A highly purified preparation of equine Leydig cells
      was obtained from a discontinuous Percoll gradient. Purity of equine Leydig cells
      was assessed using histochemical 3beta-HSD staining. Equine Leydig cells and
      selected doses of recombinant human IGF-1 (rhIGF-I; Parlow A.F., National Hormone
      and Peptide Program, Harbor-UCLA Medical Center) were added to wells of 24 or 96
      well culture plates in triplicate and cultured for 24 or 48 h under 95% air:5%
      CO(2) at 34 degrees C. After 24 or 48 h incubation, apoptotic rate was assessed
      using a Cell Death Detection ELISA kit. Significantly lower apoptotic rates were
      observed in equine Leydig cells cultured with 5, 10, or 50ng/ml of rhIGF-I
      compared with control cells cultured without rhIGF-I for 24h. Exposure to 1, 5,
      10 or 50 ng/ml of rhIGF-I significantly decreased apoptotic rate in equine Leydig
      cells cultured for 48 h. After 48 h incubation, cells were labeled with Annexin V
      and propodium iodine to determine the populations of healthy, apoptotic, and
      necrotic cells by counting stained cells using a Nikon Eclipse inverted
      fluorescence microscope. As a percentage of the total cells counted,
      significantly lower numbers of apoptotic cells were observed in cells treated
      with 10 (9%) or 50 ng/ml (10%) of rhIGF-I compared with cells cultured without
      rhIGF-I (control, 22%). In this study, the results from the two assays indicated
      that rhIGF-I protected equine Leydig cells from undergoing apoptosis during cell
      culture for 24h or 48 h. In conclusion, IGF-I may be an important
      paracrine/autocrine factor in protecting equine Leydig cells from undergoing
      apoptosis.

PMID- 21071159
TI  - The regulatory mechanism of neuromedin S on luteinizing hormone in pigs.
AB  - Neuromedin S (NMS) has been implicated in the regulation of luteinizing hormone
      (LH) secretion. However, the regulatory mechanism of NMS on LH in pigs remains
      unexplored. In the present study, we confirmed the hypothesis that the effect of
      NMS on LH could be mediated via hypothalamic melanocyte-stimulating hormones
      (MSH) neurons of ovariectomized pigs. In an immunohistological experiment, NMS
      receptor NMU2R-positive neurons were found in the paraventricular nucleus of
      hypothalamus, widely distributed in the anterior pituitary, and sparsely observed
      in the posterior pituitary. We also found that serum LH level was declined at
      between 12 and 60 min with the lowest level at 24 min after NMS injection. The
      decreased LH secretion induced by NMS could be completely abolished by
      pretreatment with melanocortin receptor-4 antagonist SHU9119, while a signal
      injection of 1.0 nM SHU9119 per se did not affect the serum LH level. Real time
      quantitative RT-PCR results showed that the expression of GnRH and LH mRNAs were
      down-regulated by NMS treatment, but their reduction was restored to normal level
      by SHU9119 treatments. The expression of NMU2R and PR mRNAs were up-regulated by
      NMS treatment, but their effects were blocked by SHU9119 treatments. The
      expression of the estrogen receptor mRNA in the pig hypothalamus and pituitary
      was unchanged under the NMS and SHU9119+NMS treatments. In summary, all results
      suggest that the inhibitory effect of NMS on LH is at least in part through its
      receptor NMU2R and mediated via MSH neurons in hypothalamus-pituitary axis of
      ovariectomized pigs.

PMID- 21071160
TI  - Analysis of 50 SNPs in CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 by MALDI-TOF
      mass spectrometry in Chinese Han population.
AB  - One of the major challenges in the near future is the identification of genes
      that affect the metabolism of different drugs. Large scale association studies
      that utilise single nucleotide polymorphisms (SNPs) have been considered a
      valuable tool for this purpose. CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 were
      found to be involved in the majority of hepatically cleared drugs. To determine
      the allele frequencies of some SNPs that may have great potential value in
      forensic science, we screened 50 SNPs in these 5 CYP genes in Chinese Han people
      using an accurate, high-throughput, cost-effective method. Primers were designed
      using the MassARRAY Assay Design software. Genomic DNA was prepared from blood
      samples obtained from individuals of Chinese Han origin. Multiplex PCR was
      performed to amplify the relevant gene fragments, and the polymorphisms were
      analysed by allele-specific primer extension followed by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). A panel of
      genomic DNA samples previously genotyped by other methods were analysed
      simultaneously for quality control, and the results demonstrated that this assay
      was 100% accurate. A total of 17 of the analysed SNPs were polymorphic. Of these
      17 SNPs, 8 (rs16947, rs28371725, rs1800754, rs4244285, rs4986893, rs12248560,
      rs3758580, rs2242480) had an allele frequency that was significantly different
      between this Chinese Han population and Caucasians (p<0.01). In addition, the
      frequencies of two of these SNPs (rs1800754, rs3758581) in our Chinese Han
      population differed significantly from the existing Chinese frequency data
      (p<0.01). The described method thus provides reliable results and enables the
      genotyping of up to thousands of samples by taking advantage of the high
      throughput MALDI-TOF technology. The results herein are now included as a
      supplement to the P450 database.

PMID- 21071161
TI  - The ability of the blowflies Calliphora vomitoria (Linnaeus), Calliphora vicina
      (Rob-Desvoidy) and Lucilia sericata (Meigen) (Diptera: Calliphoridae) and the
      muscid flies Muscina stabulans (Fallen) and Muscina prolapsa (Harris) (Diptera:
      Muscidae) to colonise buried remains.
AB  - The blowflies Calliphora vomitoria (Linnaeus), Calliphora vicina (Rob-Desvoidy)
      and Lucilia sericata (Meigen) exhibited a limited ability to colonise pig liver
      baits buried in loose soil. Calliphora vomitoria colonised baits buried at 5 cm
      but no deeper whilst C. vicina and L. sericata colonised remains at 10 cm but not
      at 20 cm. The baits were colonised by larvae hatching from eggs laid on the
      surface of the soil. Both C. vomitoria and L. sericata were able to develop from
      eggs through to adulthood on baits that were infested before being buried and the
      larvae developed at similar rates and pupariated at similar depths to larvae
      developing on baits on the soil surface. The muscid flies Muscina stabulans
      (Fallen) and Muscina prolapsa (Harris) colonised remains buried in loose soil at
      a depth of 40 cm and even when presented with baits on the soil surface their
      larvae tended to remain in the soil beneath the baits. In compacted soil, M.
      stabulans colonised baits buried at 10 cm but M. prolapsa only colonised those
      buried at 5 cm. In both muscid species, the adult flies were instantly attracted
      to feed on fresh blood and laid eggs in the soil above buried baits within 30min
      of them being introduced into the cages. The adult muscid flies did not attempt
      to burrow into the soil and their larvae colonised the baits from eggs laid on
      the soil surface. This information could be useful in determining whether a body
      was stored above ground before being buried and/or the time since burial
      occurred.

PMID- 21071162
TI  - Fibrotic lesions of the breast: radiological findings and core-neddle biopsy
      results.
AB  - OBJECTIVES: To evaluate the incidence of breast lesions with a histopathological
      diagnosis of focal fibrosis based on imaging guided core biopsy, to review the
      radiologic findings and to assess the diagnostic reliability of 14 G core needle
      biopsy. MATERIALS AND METHODS: 723 patients, who had undergone 14 G core biopsy
      and/or surgical excisions, were retrospectively analyzed. Overall, 43 lesions
      were diagnosed as focal fibrosis. Physical examination, mammography,
      ultrasonography, and follow-up findings were all reviewed. RESULTS: Radiological
      evaluation revealed that 35 (81%) lesions were solid masses. Of 35 mass lesions,
      24 (69%) were well circumscribed, the remaining 11 (31%) lesions were ill defined
      on mammograms or sonograms. None of the lesions had pathological
      microcalcifications. Three lesions were surgically excised because of radio
      pathological discordance after core needle biopsy. CONCLUSIONS: Focal fibrosis of
      the breast is a benign condition and reflects the ductal and lobular atrophy
      secondary to stromal proliferation. The radiological findings of this entity may
      vary and sometimes mimic those of malignant lesions. The incidence of focal
      fibrosis among our study population is 6% and a well-defined mass lesion is the
      most frequent finding. Core needle biopsy is a safe and reliable diagnostic
      procedure in the management of these cases.

PMID- 21071163
TI  - Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in
      patients with and without pulmonary embolism: preliminary results.
AB  - OBJECTIVES: Recently, software has been used for quantification of lung PBV,
      which can be evaluated objectively; however, this technique is yet to be
      validated. The purpose was to investigate the clinical feasibility of the
      quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in
      patients with pulmonary embolism (PE). MATERIALS AND METHODS: One hundred
      thirteen patients with clinical suspicion of PE underwent dual-energy CT
      angiography with a standard injection protocol. Patients were divided into each
      two groups with and without PE based on the presence of endoluminal clots on
      transverse diagnostic scans. We evaluated the quantification of lung PBV using a
      workstation. Associations between lung PVB and the numbers of pulmonary segments
      with PE were also evaluated. RESULTS: Thirty three of 113 (29%) patients were
      found to have endoluminal clots in the right and/or left lungs. The remaining 80
      patients did not have endoluminal clots. In 33 patients, the mean number of
      segments with endoluminal clots was 5.2+/-3.3. For patient (whole lung)-based
      analysis, in patients with and without PE, mean lung PBVs were 20.8+/-2.3 and
      28.7+/-6.8 Hounsfield Unit (HU), respectively, with a significant difference
      between the two groups (p<0.0001). In patients with PE, there was a significant
      correlation between lung PBV and the numbers of pulmonary segments with PE
      (R=0.57, p=0.0005). CONCLUSION: The findings of this preliminary study suggest
      that quantification of lung PBV may reflect the pulmonary artery perfusion, which
      is useful to evaluate pulmonary blood flow in patients with PE.

PMID- 21071164
TI  - Ultrasonographic evaluation of degenerative changes in the distal radioulnar
      joint: correlation of findings with gross anatomy and MR arthrography in
      cadavers.
AB  - OBJECTIVE: To determine the accuracy of ultrasonography (US) in the evaluation of
      degenerative changes in the distal radioulnar joint (DRUJ). METHODS AND
      MATERIALS: Ten cadaveric specimens were obtained. US evaluation of cartilage
      degeneration and thickness was performed by two independent and blinded readers
      (R1 and R2). Gross anatomy and MR arthrography evaluated by two readers in
      consensus served as the reference standard. The joint surface not accessible to
      US was measured. RESULTS: US interreader agreement was non-existent for cartilage
      thickness measurements and moderate for cartilage degeneration grading (weighted
      kappa = 0.41). Comparing US and MR imaging evaluation, there was no correlation
      between US R1 and MR imaging (Pearson correlation coefficient [PCC] = 0.352) and
      a moderate correlation between US R2 and MR imaging (PCC = 0.570) concerning
      cartilage thickness measurements. Concerning cartilage degeneration grading,
      there was a moderate to strong (R1 Spearman correlation coefficient [SCC] =
      0.729)/R2 SCC = 0.767) correlation concerning cartilage degeneration grading.
      Comparing US and gross anatomic evaluation, there was no correlation for US R1
      (PCC = 0.220) and a strong correlation for US R2 (PCC = 0.922) concerning
      cartilage thickness measurements, and a strong to moderate correlation (R1 SCC =
      0.808/R2 SCC = 0.597) concerning cartilage degeneration grading. The mean sector
      of the articular surface of the ulna head not accessible to US was 13 degrees .
      CONCLUSION: In conclusion the DRUJ is accessible to US except in the central 13
      degrees  sector of the joint surface. US was approved to be sufficient in
      demonstrating advanced stages of cartilage degeneration. Thus, US of the DRUJ is
      recommended in patients suffering from ulnar-sided wrist pain.

PMID- 21071165
TI  - A HPLC-MS method for the simultaneous quantification of fourteen antiretroviral
      agents in peripheral blood mononuclear cell of HIV infected patients optimized
      using medium corpuscular volume evaluation.
AB  - A sensitive and accurate high performance liquid chromatography-mass
      spectrometric (HPLC-MS) method for the intracellular determination of 14
      antiretroviral drugs in peripheral blood mononuclear cells (PBMCs) for HIV+
      patients was validated. PBMCs are isolated by Ficoll density gradient
      centrifugation and cells count and the relative mean volume is performed with a
      Coulter((r)) instrument. Extraction of drugs from PBMCs pellets was obtained with
      methanol:water (70:30, v/v), with quinoxaline added as internal standard, after a
      sonication step. Supernatant was dried and then dissolved in water/acetonitrile
      (60/40, v/v), before injection into a 2.1 mm*150 mm Atlantis((r)) T3 3MU column.
      Chromatographic separations were performed using a gradient program with a
      mixture of water (0.05% formic acid), as mobile phase A and acetonitrile (0.05%
      formic acid), as mobile phase B. Analytes quantification was performed by electro
      spray ionisation-single quadrupole mass spectrometry using the selected ion
      recording (SIR) detection mode. The positive ionization was used for the HIV
      protease inhibitors (PIs) indinavir, saquinavir, nelfinavir, nelfinavir M8
      metabolite, amprenavir, darunavir, atazanavir, ritonavir, lopinavir, tipranavir,
      the integrase inhibitor (II) raltegravir and the non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) nevirapine and etravirine, while the negative
      ionization is applied for efavirenz. The calibration curves were built using
      blank PBMCs spiked with antiretroviral drugs at concentrations ranging from 0.1
      to 32 ng/mL (1-320 ng/mL for tipranavir) and fitted to a quadratic regression
      model weighted by 1/X. The mean extraction recovery for all PIs, II and NNRTIs
      was always above 82%. The method was precise, with a range of intra/inter-day
      percent standard deviation within 2.6-14.8%, and accurate with mean of percent
      coefficient of variation (CV%) from nominal values -7.85 to +9.7%. Each drug
      concentration evaluated was expressed in ng/mL and optimized using each patient
      medium corpuscolar volume and cell number. This analytical method is routinely
      used in our clinical research center for the assessment of intracellular levels
      of all PIs, raltegravir and NNRTIs commercially available at present.

PMID- 21071166
TI  - Do cognitive perceptions influence CPAP use?
AB  - OBJECTIVE: Nonadherence to CPAP increases health and functional risks of
      obstructive sleep apnea. The study purpose was to examine if disease and
      treatment cognitive perceptions influence short-term CPAP use. METHODS: A
      prospective longitudinal study included 66, middle-aged (56.7 +/- 10.7 yr)
      subjects (34 [51.5%] Caucasians; 30 [45.4%] African Americans) with severe OSA
      (AHI 43.5 events/hr +/- 24.6). Following full-night diagnostic/CPAP
      polysomnograms, home CPAP use was objectively measured at 1 week and 1 month. The
      Self Efficacy Measure for Sleep Apnea (SEMSA) questionnaire, measuring risk
      perception, outcome expectancies, and self-efficacy, was collected at baseline,
      post-CPAP education, and after 1 week CPAP treatment. Regression models were
      used. RESULTS: CPAP use at one week was 3.99 +/- 2.48 h/night and 3.06 +/- 2.43
      h/night at one month. No baseline SEMSA domains influenced CPAP use. Post
      education self-efficacy influenced one week CPAP use (1.52 +/- 0.53, p=0.007).
      Self-efficacy measured post-education and after one week CPAP use also influenced
      one month CPAP (1.40 +/- 0.52, p=0.009; 1.20 +/- 0.50, p=0.02, respectively).
      CONCLUSION: Cognitive perceptions influence CPAP use, but only within the context
      of knowledge of CPAP treatment and treatment use. PRACTICE IMPLICATIONS: Patient
      education is important to OSA patients' formulation of accurate and realistic
      disease and treatment perceptions which influence CPAP adherence.

PMID- 21071167
TI  - Comparing narrative and informational videos to increase mammography in low
      income African American women.
AB  - OBJECTIVE: Compare effects of narrative and informational videos on use of
      mammography, cancer-related beliefs, recall of core content and a range of
      reactions to the videos. METHOD: African American women (n=489) ages 40 and older
      were recruited from low-income neighborhoods in St. Louis, MO and randomly
      assigned to watch a narrative video comprised of stories from African American
      breast cancer survivors (Living Proof) or a content-equivalent informational
      video using a more expository and didactic approach (Facts for Life). Effects
      were measured immediately post-exposure and at 3- and 6-month follow-up. RESULTS:
      The narrative video was better liked, enhanced recall, reduced counterarguing,
      increased breast cancer discussions with family members and was perceived as more
      novel. Women who watched the narrative video also reported fewer barriers to
      mammography, more confidence that mammograms work, and were more likely to
      perceive cancer as an important problem affecting African Americans. Use of
      mammography at 6-month follow-up did not differ for the narrative vs.
      informational groups overall (49% vs. 40%, p=.20), but did among women with less
      than a high school education (65% vs. 32%, p<.01), and trended in the same
      direction for those who had no close friends or family with breast cancer (49%
      vs. 31%, p=.06) and those who were less trusting of traditional cancer
      information sources (48% vs. 30%, p=.06). CONCLUSIONS: Narrative forms of
      communication may increase the effectiveness of interventions to reduce cancer
      health disparities. PRACTICE IMPLICATIONS: Narratives appear to have particular
      value in certain population sub-groups; identifying these groups and matching
      them to specific communication approaches may increase effectiveness.

PMID- 21071168
TI  - The endoscopic treatment of sciatic nerve entrapment/deep gluteal syndrome.
AB  - PURPOSE: The purpose of this study was to investigate the historical, clinical,
      and radiographic presentation of deep gluteal syndrome (DGS) patients, describe
      the endoscopic anatomy associated with DGS, and assess the effectiveness of
      endoscopic surgical decompression for DGS. METHODS: Sciatic nerve entrapment was
      diagnosed in 35 patients (28 women and 7 men). Portals for inspection of the
      posterior peritrochanteric space (subgluteal space) of the hip were used as well
      as an auxiliary posterolateral portal. Patients were treated with sciatic nerve
      decompression by resection of fibrovascular scar bands, piriformis tendon
      release, obturator internus, or quadratus femoris or by hamstring tendon
      scarring. Postoperative outcomes were evaluated with the modified Harris Hip
      Score (MHHS), verbal analog scale (VAS) pain score, and a questionnaire related
      specifically to sciatic hip pain. RESULTS: The mean patient age was 47 years
      (range, 20 to 66 years). The mean duration of symptoms was 3.7 years (range, 1 to
      23 years). The mean preoperative VAS score was 6.9 +/- 2.0, and the mean
      preoperative MHHS was 54.4 +/- 13.1 (range, 25.3 to 79.2). Of the patients, 21
      reported preoperative use of narcotics for pain; 2 continued to take narcotics
      postoperatively (unrelated to initial complaint). The mean time of follow-up was
      12 months (range, 6 to 24 months). The mean postoperative MHHS increased to 78.0
      and VAS score decreased to 2.4. Eighty-three percent of patients had no
      postoperative sciatic sit pain (inability to sit for >30 minutes). CONCLUSIONS:
      Endoscopic decompression of the sciatic nerve appears useful in improving
      function and diminishing hip pain in sciatic nerve entrapment/DGS.

PMID- 21071169
TI  - The German Hip Outcome Score: validation in patients undergoing surgical
      treatment for femoroacetabular impingement.
AB  - PURPOSE: To cross-culturally adapt and validate the Hip Outcome Score (HOS) for
      use in German-speaking patients undergoing surgical treatment for
      femoroacetabular impingement. METHODS: After cross-cultural adaptation (German
      language version of the HOS [HOS-D]), the following metric properties of the
      questionnaire were assessed in 85 consecutive patients (mean age, 33.4 years; 36
      women) undergoing hip arthroscopy or surgical hip dislocation: feasibility,
      reliability, internal consistency, and construct validity (correlation with
      Western Ontario and McMaster Universities Arthritis Index, Oxford Hip Score,
      Short Form 12, and University of California, Los Angeles activity scale). We
      calculated floor and ceiling effects taking the minimal detectable change into
      account. RESULTS: The activities of daily living subscale of the HOS-D could be
      scored in all cases and the sport subscale in all but one. The HOS-D scores were
      highly reproducible with intraclass correlation coefficients of 0.94 for the
      activities of daily living subscale and 0.89 for the sport subscale. Internal
      consistency was confirmed by Cronbach alpha values >0.90 for both subscales.
      Correlation coefficients with the other measures ranged from -0.08 (Mental
      Component Scale of Short Form 12) to -0.90 (Western Ontario and McMaster
      Universities Arthritis Index function subscale). CONCLUSIONS: The HOS-D is a
      reliable and valid self-assessment tool for patients undergoing surgical
      femoroacetabular impingement treatment. By use of the HOS, comparisons between
      studies and treatment regimens involving either German- or English-speaking
      patients are now possible. LEVEL OF EVIDENCE: Level I, testing of previously
      developed diagnostic criteria in a series of consecutive patients with
      universally applied gold standard.

PMID- 21071170
TI  - Assessment of a new averaging algorithm to increase the sensitivity of axial eye
      length measurement with optical biometry in eyes with dense cataract.
AB  - PURPOSE: To assess the capability of new software to decrease the proportion of
      eyes that have insufficient signal-to-noise ratio (SNR) in optical biometry.
      SETTING: Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
      DESIGN: Evaluation of diagnostic test or technology. METHODS: In a prospective
      study, consecutive cataract patients coming for biometry who were unsuccessfully
      measured with the former software (version 4) of the IOLMaster partial coherence
      interferometry (PCI) device were reevaluated with the new composite software
      (version 5). Subsequently, in a retrospective study, consecutive cataract
      patients were measured with software version 5. For unsuccessful scans, the type
      and intensity of cataract were assessed at the slitlamp. RESULTS: Altogether,
      2713 eyes (1956 patients) were included in the study. The prospective study
      comprised 458 eyes (244 patients), 10.6% of which could not be measured
      successfully with software version 4. With the composite software, 30% of cases
      were measured successfully, with a higher proportion (42%) in the posterior
      subcapsular cataract subgroup. In the retrospective study, of 2255 eyes (1712
      patients), 4.7% were not measured successfully using the new algorithm because of
      white cataract (70 eyes), posterior subcapsular cataract (14 eyes), or dense
      nuclear cataract combined with posterior subcapsular cataract (13 eyes) or for
      other reasons (8 eyes). CONCLUSION: The composite software (version 5) enhanced
      the SNR, allowing valid measurements in eyes in which optical biometry had
      previously failed, especially in cases of posterior subcapsular cataract.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned. Additional disclosure is found in the footnotes.

PMID- 21071171
TI  - Effectiveness of virtual reality using Wii gaming technology in children with
      Down syndrome.
AB  - This quasi-experimental study compared the effect of standard occupational
      therapy (SOT) and virtual reality using Wii gaming technology (VRWii) on children
      with Down syndrome (DS). Children (n = 105) were randomly assigned to
      intervention with either SOT or VRWii, while another 50 served as controls. All
      children were assessed with measures of sensorimotor functions. At post
      intervention, the treatment groups significantly outperformed the control group
      on all measures. Participants in the VRWii group had a greater pre-post change on
      motor proficiency, visual-integrative abilities, and sensory integrative
      functioning. Virtual reality using Wii gaming technology demonstrated benefit in
      improving sensorimotor functions among children with DS. It could be used as
      adjuvant therapy to other proven successful rehabilitative interventions in
      treating children with DS.

PMID- 21071172
TI  - Postural analysis in time and frequency domains in patients with Ehlers-Danlos
      syndrome.
AB  - The goal of this work is to analyze postural control in Ehlers-Danlos syndrome
      (EDS) participants in time and frequency domain. This study considered a
      pathological group composed by 22 EDS participants performing a postural test
      consisting in maintaining standing position over a force platform for 30s in two
      conditions: open eyes (OE) and closed eyes (CE). In order to compare pathological
      group we acquired in the same conditions a control group composed by 20 healthy
      participants. The obtained center of pressure (COP) signal was analyzed in time
      and frequency domain using an AR model. Results revealed differences between
      pathological and control group: EDS participants pointed out difficulties in
      controlling COP displacements trying to keep it inside the BOS in AP direction
      and for this reason increased the use of ML mechanism in order to avoid the risk
      of fall. Also in CE conditions they demonstrated more difficulties in maintaining
      posture revealing the proprioceptive system is impaired, due to ligament laxity
      that characterized EDS participants. Frequency domain analysis showed no
      differences between the two groups, affirming that the changes in time domain
      reflected really the impairment to the postural control mechanism and not a
      different strategy assumed by EDS participants. These data could help in decision
      making process to establish a correct rehabilitation approach, based on the
      reinforcing of muscle tone to supply the ligament laxity in order to prevent
      risks of falls and its consequences.

PMID- 21071173
TI  - The CAREQOL-MS was a useful instrument to measure caregiver quality of life in
      multiple sclerosis.
AB  - OBJECTIVE: To develop and test the first specific instrument for assessing
      caregiver health-related quality of life (HRQOL) in multiple sclerosis (MS)
      (CAREQOL-MS). STUDY DESIGN AND SETTING: Questionnaire items were derived from a
      literature review and the views of patients, caregivers, and experts. Instrument
      was reduced after the analyses of caregivers' interviews and experts' opinions.
      CAREQOL-MS psychometric properties were assessed in 276 MS caregivers. RESULTS:
      The final version consisted of 24 items (five subscales) and was free of floor or
      ceiling effects. For subscales, the Cronbach's alpha coefficient ranged from 0.75
      to 0.90. The item-total correlation was 0.62-0.74 for subscale I (physical
      burden/global health); 0.56-0.74 for subscale II (social impact); 0.52-0.62 for
      subscale III (emotional impact), and 0.58-0.65 for subscale IV (need of help);
      subscale V (emotional reactions) had only two items. The intraclass correlation
      coefficient (0.96 for the total score; 0.75-0.95 for subscales) suggested
      satisfactory reproducibility. Association was close between CAREQOL-MS subscales
      and the Zarit burden interview and moderate with short form 36 mental/physical
      components. CAREQOL-MS subscales scores significantly increased (worse HRQOL)
      with increasing caregivers' age and Expanded Disability Status Scale. The
      standard error of the measurement ranged from 0.91 to 2.43 for subscales.
      CONCLUSIONS: Our results provided initial evidence of the usefulness and
      satisfactory psychometric properties of the CAREQOL-MS.

PMID- 21071174
TI  - Development quality criteria to evaluate nontherapeutic studies of incidence,
      prevalence, or risk factors of chronic diseases: pilot study of new checklists.
AB  - OBJECTIVE: To develop two checklists for the quality of observational studies of
      incidence or risk factors of diseases. STUDY DESIGN AND SETTING: Initial
      development of the checklists was based on a systematic literature review. The
      checklists were refined after pilot trials of validity and reliability were
      conducted by seven experts, who tested the checklists on 10 articles. RESULTS:
      The checklist for studies of incidence or prevalence of chronic disease had six
      criteria for external validity and five for internal validity. The checklist for
      risk factor studies had six criteria for external validity, 13 criteria for
      internal validity, and two aspects of causality. A Microsoft Access database
      produced automated standardized reports about external and internal validities.
      Pilot testing demonstrated face and content validities and discrimination of
      reporting vs. methodological qualities. Interrater agreement was poor. The
      experts suggested future reliability testing of the checklists in systematic
      reviews with preplanned protocols, a priori consensus about research-specific
      quality criteria, and training of the reviewers. CONCLUSION: We propose
      transparent and standardized quality assessment criteria of observational studies
      using the developed checklists. Future testing of the checklists in systematic
      reviews is necessary to develop reliable tools that can be used with confidence.

PMID- 21071175
TI  - Novel autoantibody markers for early and seronegative rheumatoid arthritis.
AB  - Approximately one-third of rheumatoid arthritis (RA) patients are seronegative
      for the 2 serological RA markers, rheumatoid factor (RF) and antibodies against
      cyclic citrullinated peptides (ACCP). Moreover, the sensitivities of both markers
      are lower in the diagnostically important early disease phase. The aim of this
      study was to identify additional autoantibody markers for early RA and for RF
      negative, ACCP-negative (seronegative) RA. We screened an RA synovium cDNA phage
      display library with autoantibodies in plasma from 10 early (symptoms of maximum
      1 year) and 10 seronegative (RF-negative, ACCP-negative) RA patients with
      validation in 72 additional RA patients and 121 controls (38 healthy controls, 43
      patients with other inflammatory rheumatic diseases, 20 osteoarthritis patients
      and 20 subjects with mechanical joint complaints). Fourteen novel autoantibodies
      were identified that showed a 54% sensitivity and 90% specificity for RA. For 11
      of these autoantibodies, an exclusive presence was demonstrated in RA patients
      (100% specificity, 37% sensitivity) as compared to controls. All early RA
      patients were positive for at least one of the identified autoantibodies and
      antibody-positivity was associated with a shorter disease duration (P = 0.0087).
      52% of RA patients who initially tested negative for RF and ACCP, tested positive
      for at least one of the 14 novel autoantibodies, resulting in a 19% increase in
      sensitivity compared to current serological testing. Moreover, 5 identified
      autoantibodies were detected more frequently in seronegative RA patients,
      indicating that these autoantibodies constitute novel candidate markers for this
      RA subtype. We demonstrated that the targets of 3 of these 5 autoantibodies had
      an increased expression in RA synovial tissue compared to control synovial
      tissue, pointing towards a biological rationale for these auto antibody targets
      in RA. In conclusion, we identified novel candidate autoantibody markers for RA
      that can be detected in early and seronegative RA patients indicating the
      potential added value for RA diagnostics.

PMID- 21071176
TI  - Association study of lamotrigine-induced cutaneous adverse reactions and HLA
      B*1502 in a Han Chinese population.
AB  - Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among
      the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte
      antigen (HLA)-B*1502 has been strongly associated with CBZ-induced Stevens
      Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this
      relationship, we performed high-resolution HLA genotyping on LTG-tolerant
      controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging
      from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs
      (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls,
      and 71 healthy volunteers were enrolled. The differences in the starting dosage
      of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not
      statistically significant. HLA-B*1502 frequency was 33.3% (1/3; LTG-induced
      SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant
      group), and 8.5% (6/71; healthy volunteers). There was no significant difference
      in the frequency of subjects with the HLA-B*1502 allele between the SJS/TEN group
      and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy
      volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups
      (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI
      0.17-23.9). None of the HLA alleles detected were associated with LTG-induced
      cADRs. In conclusion, HLA-B*1502 and other HLA alleles are not directly
      associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated
      with an increased risk of LTG-induced SJS/TEN could not be excluded.

PMID- 21071177
TI  - A novel implantable vagus nerve stimulation system (ADNS-300) for combined
      stimulation and recording of the vagus nerve: pilot trial at Ghent University
      Hospital.
AB  - PURPOSE: Vagus nerve stimulation (VNS) is an established treatment for refractory
      epilepsy. The ADNS-300 is a new system for VNS that includes a rechargeable
      stimulus generator and an electrode for combined stimulation and recording. In
      this feasibility study, three patients were implanted with ADNS-300 for
      therapeutic VNS. In addition, compound action potentials (CAPs) were recorded to
      evaluate activation of the vagus nerve in response to VNS. METHODS: Three
      patients were implanted with a cuff-electrode around the left vagus nerve, that
      was connected to a rechargeable pulse generator under the left clavicula. Two
      weeks after surgery, therapeutic VNS (0.25-1.25 mA, 500 MUs, 30s on, 10 min off
      and 30Hz) was initiated and stimulus-induced CAPs were recorded. RESULTS: The
      ADNS-300 system was successfully implanted in all three patients and patients
      were appropriately stimulated during six months of follow-up. A reduction in
      seizure frequency was demonstrated in two patients (43% and 40% in patients 1 and
      3, respectively), while in patient 2 seizure frequency remained unchanged. CAPs
      could be recorded in patients 1 and 2, proving stimulation-induced activation of
      the vagus nerve. CONCLUSION: This feasibility study demonstrates that the ADNS
      300 system can be used for combined therapeutic stimulation (in 3/3 patients) and
      recording of CAPs in response to VNS (in 2/3 patients) up to three weeks after
      surgery. Implantation in a larger number of patients will lead to a better
      understanding of the electrophysiology of the vagus nerve, which in turn could
      result in more adequate and individualized VNS parameter choice.

PMID- 21071178
TI  - Features of the K-complex waves in refractory nocturnal frontal lobe epilepsy.
AB  - PURPOSE: To investigate the features of the K-complex (Kc) in refractory
      nocturnal frontal lobe epilepsy (NFLE) and its relationship with spike discharges
      (Sds) and clinical seizures. METHODS: Long-term video-electroencephalographic
      (VEEG) monitoring was used to collect Kc data from NFLE patients and age- and sex
      matched controls. We compared the morphological and frequency changes in Kcs
      between the intractable NFLE group and the control group. Also, the morphological
      changes in Kcs with Sds and seizures were compared with the other Kcs in NFLE
      patients. RESULTS: In the NFLE group, frequency, amplitude, and rising slope
      (except duration) were higher than in the control group. Out of the 30 seizures
      recorded, nine (30%) commenced after a Kc. These Kcs had higher amplitudes than
      the other Kcs in the NFLE group; there was no difference in duration or rising
      slope. Additionally, 28 (13.86%) of 202 Kcs of the NFLE group occurred in
      conjunction with Sds; there were no obvious morphological differences compared
      with other Kcs. CONCLUSION: Kc activity increases in NFLE, especially prior to a
      clinical seizure. This reflects an unstable sleep condition, which suggests a
      correlation between Kc and epileptic activities including seizures and Sds.

PMID- 21071179
TI  - The metabolic syndrome and its constituting variables in atypical antipsychotic
      treated subjects: comparison with other drug treatments, drug-free psychiatric
      patients, first-degree relatives and the general population in Venezuela.
AB  - BACKGROUND: Few studies on the association between atypical antipsychotic drug
      (AAP) administration and metabolic dysfunction have concurrently evaluated the
      general population (GP), other psychotropic drug treatments and drug-free
      psychiatric patients. METHODS: We assessed the frequency of the metabolic
      syndrome (MS) according to the National Cholesterol Education Program criteria
      (NCEP) and its constituting variables in a GP sample (n=271) and in patients
      receiving, for at least three consecutive months, antiepileptic drugs (n=93),
      olanzapine (n=162), clozapine (n=105), typical antipsychotics (n=117), other AAP
      (n=58), other psychotropic drugs (n=185), and drug-free individuals (n=636).
      Subjects were clinically classified as schizophrenia, bipolar or other axis I
      disorders (DSM-IV-RT), and as first-degree relatives of each diagnostic group.
      RESULTS: The MS was detected in 26.6% of the GP (95% confidence interval: 21.5
      31.8). No diagnostic or treatment group had a significantly higher age-adjusted
      frequency than the GP (p>0.05). Treatment duration did not significantly affect
      the results. However, significant differences were observed in the frequency of
      abnormal MS constituting variables in comparison to the GP. For example,
      schizophrenia patients and their relatives, bipolar subjects and olanzapine- and
      clozapine-treated patients had higher abnormal waist circumference values. In
      addition, bipolar patients and their relatives and subjects treated with
      olanzapine and other AAPs had higher frequencies of abnormal glucose levels.
      Neither schizophrenia nor bipolar patients in the diagnostic categories nor the
      olanzapine or the clozapine groups displayed higher proportions of abnormal
      triglycerides, high density cholesterol or blood pressure levels than the GP.
      CONCLUSIONS: While we did not demonstrate an increased frequency of the MS in AAP
      treated subjects, our results confirm that specific metabolic variables must be
      monitored in psychiatric patients. Besides they stress the importance, in
      epidemiological studies, of concurrently comparing the figures recorded in AAP
      treated patients with those obtained in the local GP, other drug treatment groups
      and drug-free subjects when referring to the magnitude of the metabolic effects
      of specific antipsychotic agents.

PMID- 21071180
TI  - Small cutaneous wounds induce telogen to anagen transition of murine hair
      follicle stem cells.
AB  - BACKGROUND: Recent studies suggest that large (>1 cm) diameter circular cutaneous
      wounds induce follicular neogenesis in mice. However, the effects of non-circular
      wounds or smaller circular wounds on the hair follicle cycle remain poorly
      understood. OBJECTIVE: We investigated whether non-circular wounds or smaller
      (<=1 cm) circular wounds could induce early entry of hair follicle stem cells
      into anagen. METHODS: We created different shaped and sized full-thickness
      incisional wounds on the dorsal skin of 6-wk old mice (BALB/c, C57BL/6, and CD1),
      and then assessed for hair growth, wound contraction rates, and growth factor
      and/or immunomodulatory cytokine involvement. RESULTS: By day 16 and through day
      26 post-wounding, we observed hair growth in the skin around the wound, but not
      in distant unwounded skin of BALB/c and C57BL/6 mice. In contrast, CD1 mice
      showed hair growth in both the wounded and unwounded skin. In all mice, the hair
      growth pattern was independent of wound type. The area of hair growth induced by
      a 2 cm linear wound was roughly 2-fold that induced by a 1 cm linear wound and 4
      fold that of a 0.5 cm linear wound. Increased gamma-glutamyl transpeptidase
      activity was observed in hair follicles growing in the wounded area as well as an
      up to 8-fold upregulation of Wnt- and Shh-dependent signaling, consistent with
      anagen growth. CONCLUSION: Our data strongly support that small cutaneous wounds
      induce telogen to anagen transition of murine hair follicle stem cells.

PMID- 21071181
TI  - Validation of the Peritraumatic Dissociative Experiences Questionnaire and
      Peritraumatic Distress Inventory in school-aged victims of road traffic
      accidents.
AB  - BACKGROUND: Although the reliable and valid Peritraumatic Distress Inventory (PDI
      C) and Peritraumatic Dissociative Experiences Questionnaire (PDEQ) are useful for
      identifying adults at risk of developing acute and chronic posttraumatic stress
      disorder (PTSD), they have not been validated in school-aged children and their
      predictive values remain unknown in this population. This study aims to assess
      the psychometric properties of the children versions of these two measures (PDI-C
      and PDEQ-C) in a sample of French-speaking school-children. METHODS: One-hundred
      and thirty-three consecutive victims of road traffic accidents, aged 8-15 years,
      were recruited into this longitudinal study via the emergency room. The
      peritraumatic reactions were assessed at baseline and PTSD symptoms were assessed
      1 month later. RESULTS: Cronbach's alpha coefficients were 0.8 and 0.77 for the
      PDI-C and PDEQ-C, respectively. The 1-month test-retest correlation coefficient
      (n=33) was 0.77 for both measures. The PDI-C demonstrated a two-factor structure
      while the PDEQ-C displayed a one-factor structure. As with adults, the two
      measures were intercorrelated (r=0.52) and correlated with subsequent PTSD
      symptoms and diagnosis (r=0.21-0.56; P<0.05). CONCLUSIONS: The children versions
      of the PDI and PDEQ are reliable and valid in children.

PMID- 21071184
TI  - A call for more care when investigating the cannabis-psychosis link.

PMID- 21071182
TI  - Mindfulness practice leads to increases in regional brain gray matter density.
AB  - Therapeutic interventions that incorporate training in mindfulness meditation
      have become increasingly popular, but to date little is known about neural
      mechanisms associated with these interventions. Mindfulness-Based Stress
      Reduction (MBSR), one of the most widely used mindfulness training programs, has
      been reported to produce positive effects on psychological well-being and to
      ameliorate symptoms of a number of disorders. Here, we report a controlled
      longitudinal study to investigate pre-post changes in brain gray matter
      concentration attributable to participation in an MBSR program. Anatomical
      magnetic resonance (MR) images from 16 healthy, meditation-naive participants
      were obtained before and after they underwent the 8-week program. Changes in gray
      matter concentration were investigated using voxel-based morphometry, and
      compared with a waiting list control group of 17 individuals. Analyses in a
      priori regions of interest confirmed increases in gray matter concentration
      within the left hippocampus. Whole brain analyses identified increases in the
      posterior cingulate cortex, the temporo-parietal junction, and the cerebellum in
      the MBSR group compared with the controls. The results suggest that participation
      in MBSR is associated with changes in gray matter concentration in brain regions
      involved in learning and memory processes, emotion regulation, self-referential
      processing, and perspective taking.

PMID- 21071185
TI  - Mechanisms of fibrinogen-acebutolol interactions: Insights from DSC, CD and LS.
AB  - The complex formed due to the interaction of the amphiphilic betablocker
      acebutolol with fibrinogen in a buffer solution (50mN glycine, pH of 8.5) has
      been investigated using a multipronged physicochemical approach. Differential
      scanning calorimetry measurements of the complexes have shown no reversibility of
      thermal denaturation as indicated by the three observed peaks and the opposite
      role that acebutolol plays in the folding different domains of the fibrinogen
      molecule and the stability of such domains. While circular dichroism measurements
      have revealed that interaction of acebutolol with fibrinogen affects the protein
      secondary structure to a different extent depending on the temperature and drug
      concentration, dynamic light scattering analysis showed evidence for protein
      aggregation mainly to tetramers and dimers.

PMID- 21071186
TI  - SDS induced molten globule state of heynein; a new thiol protease: Evidence of
      domains and their sequential unfolding.
AB  - The molten globule state can be an intermediate in the protein-folding pathway
      and its detailed description can help understand the protein folding and an
      insight into the molecular structure of a protein. Sodium dodecyl sulfate (SDS),
      an anionic surfactant is known to induce molten globule sate in some proteins.
      SDS-induced changes in heynein were monitored by CD, fluorescence, 8-anilino-1
      napthalenesulfonic acid (ANS) binding and proteolytic activity measurements. An
      enhancement in the alpha-helicity of protein with increasing concentration of SDS
      along with exposure of tryptophans is seen. At a concentration of SDS (~2mM)
      heynein loses activity and rigid tertiary structure but possesses considerable
      amount of secondary structure along with strong ANS binding, indicating the
      presence of an intermediate state, which is like molten globule state seen in the
      case heynein. Chemical and temperature induced unfolding of SDS-induced state of
      heynein is non-cooperative contrary to the protein in the absence of detergent.
      Further, the cooperative unfolding transition curve of heynein in the absence of
      SDS intersects at a point where the second transition of SDS-induced state starts
      suggesting that the molecule of heynein consist of at least two structural
      domains which are stabilized differentially and unfolds sequentially. Enhancement
      of alpha-helicity of heynein in the presence of SDS suggests the alpha-rich
      domain of the protein was stabilized and unfold later as compared with beta-rich
      domain during temperature and chemical induced denaturation. Equilibrium
      unfolding pathway of heynein in SDS-induced state provides knowledge of the
      structure and stability of this plant cysteine protease at domain level.

PMID- 21071187
TI  - Chitosan nanocapsules: Effect of chitosan molecular weight and acetylation degree
      on electrokinetic behaviour and colloidal stability.
AB  - In recent years, chitosan nanocapsules have shown promising results as carriers
      for oral drug or peptide delivery. The success in their applicability strongly
      depends on the stability of these colloidal systems passing through the digestive
      tract. In gastric fluids, clear stability comes from the high surface charge
      density of the chitosan shell, which is completely charged at acidic pH values.
      However, in the intestinal fluid (where the pH is almost neutral) the effective
      charge of these nanocapsules approaches zero, and the electrostatic forces cannot
      provide any stabilization. Despite the lack of surface charge, chitosan
      nanocapsules remain stable in simulated intestinal fluids. Recently, we have
      demonstrated that this anomalous stability (at zero charge) is owed to short
      range repulsive forces that appear between hydrophilic particles when immersed in
      saline media. The present work examines the influence of the chitosan
      hydrophobicity, as well as molecular weight, in the stability of different
      chitosan nanocapsules. A study has been made of the size, polydispersity,
      electrophoretic mobility, and colloidal stability of eight core-shell nanocapsule
      systems, in which the chitosan-shell properties have been modified using low
      molecular-weight (LMW) and high-molecular-weight (HMW) chitosan chains having
      different degrees of acetylation (DA). With regard to the stability mediated by
      repulsive hydration forces, the LMW chitosan provided the best results. In
      addition, contrary to initial expectations, greater stability (also mediated by
      hydration forces) was found in the samples formed with chitosan chains of high DA
      values (i.e. with less hydrophilic chitosan). Finally, a theoretical treatment
      was also tested to quantify the hydrophilicity of the chitosan shells.

PMID- 21071188
TI  - Vesicle and bilayer formation of diphytanoylphosphatidylcholine (DPhPC) and
      diphytanoylphosphatidylethanolamine (DPhPE) mixtures and their bilayers'
      electrical stability.
AB  - Lipid bilayers are of interest in applications where a cell membrane mimicking
      environment is desired. The performance of the lipid bilayer is largely dependent
      on the physical and chemical properties of the component lipids. Lipid bilayers
      consisting of phytanoyl lipids have proven to be appropriate choices since they
      exhibit high mechanical and chemical stability. In addition, such bilayers have
      high electrical resistances. Two different phytanoyl lipids, 1,2-diphytanoyl-sn
      glycero-3-phosphocholine (DPhPC) and 1,2-diphytanoyl-sn-glycero-3
      phosphoethanolamine (DPhPE), and various combinations of the two have been
      investigated with respect to their behavior in aqueous solutions, their
      interactions with solid surfaces, and their electrical stability. Dynamic light
      scattering, nuclear magnetic resonance diffusion, and cryogenic transmission
      electron microscopy measurements showed that pure DPhPC as well as mixtures of
      DPhPC and DPhPE consisting of greater than 50% (mol%) DPhPC formed unilamellar
      vesicles. If the total lipid concentration was greater than 0.15g/l, then the
      vesicles formed solid-supported bilayers on plasma-treated gold and silica
      surfaces by the process of spontaneous vesicle adsorption and rupture, as
      determined by quartz crystal microbalance with dissipation monitoring and atomic
      force microscopy. The solid-supported bilayers exhibited a high degree of
      viscoelasticity, probably an effect of relatively high amounts of imbibed water
      or incomplete vesicle fusion. Lipid compositions consisting of greater than 50%
      DPhPE formed small flower-like vesicular structures along with discrete liquid
      crystalline structures, as evidenced by cryogenic transmission electron
      microscopy. Furthermore, electrophysiology measurements were performed on
      bilayers using the tip-dip methodology and the bilayers' capacity to retain its
      electrical resistance towards an applied potential across the bilayer was
      evaluated as a function of lipid composition. It was shown that the lipid ratio
      significantly affected the bilayer's electrical stability, with pure DPhPE having
      the highest stability followed by 3DPhPC:7DPhPE and 7DPhPC:3DPhPE in decreasing
      order. The bilayer consisting of 5DPhPC:5DPhPE had the lowest stability towards
      the applied electrical potential.

PMID- 21071189
TI  - Single molecule atomic force microscopy and force spectroscopy of chitosan.
AB  - Atomic force microscopy (AFM) and AFM-based force spectroscopy was used to study
      the desorption of individual chitosan polymer chains from substrates with varying
      chemical composition. AFM images of chitosan adsorbed onto a flat mica substrate
      show elongated single strands or aggregated bundles. The aggregated state of the
      polymer is consistent with the high level of flexibility and mobility expected
      for a highly positively charged polymer strand. Conversely, the visualization of
      elongated strands indicated the presence of stabilizing interactions with the
      substrate. Surfaces with varying chemical composition (glass, self-assembled
      monolayer of mercaptoundecanoic acid/decanethiol and polytetrafluoroethylene
      (PTFE)) were probed with chitosan modified AFM tips and the corresponding
      desorption energies, calculated from plateau-like features, were attributed to
      the desorption of individual polymer strands. Desorption energies of 2.0+/
      0.3*10(-20)J, 1.8+/-0.3*10(-20)J and 3.5+/-0.3*10(-20)J were obtained for glass,
      SAM of mercaptoundecanoic/dodecanethiol and PTFE, respectively. These single
      molecule level results can be used as a basis for investigating chitosan and
      chitosan-based materials for biomaterial applications.

PMID- 21071190
TI  - [Drugs news].

PMID- 21071191
TI  - Cercozoa comprises both EF-1alpha-containing and EFL-containing members.
AB  - Elongation factor 1alpha (EF-1alpha) and elongation factor-like protein (EFL) are
      considered to be functionally equivalent proteins involved in peptide synthesis.
      Eukaryotes can be fundamentally divided into 'EF-1alpha-containing' and 'EFL
      containing' types. Recently, EF-1alpha and EFL genes have been surveyed across
      the diversity of eukaryotes to explore the origin and evolution of EFL genes.
      Although the phylum Cercozoa is a diverse group, gene data for either EFL or EF
      1alpha are absent from all cercozoans except chlorarachniophytes which were
      previously defined as EFL-containing members. Our survey revealed that two
      members of the cercozoan subphylum Filosa (Thaumatomastix sp. and strain YPF610)
      are EFL-containing members. Importantly, we identified EF-1alpha genes from two
      members of Filosa (Paracercomonas marina and Paulinella chromatophora) and a
      member of the other subphylum Endomyxa (Filoreta japonica). All cercozoan EFL
      homologues could not be recovered as a monophyletic group in maximum-likelihood
      and Bayesian analyses, suggesting that lateral gene transfer was involved in the
      EFL evolution in this protist assemblage. In contrast, EF-1alpha analysis
      successfully recovered a monophyly of three homologues sampled from the two
      cercozoan subphyla. Based on the results, we postulate that cercozoan EF-1alpha
      genes have been vertically inherited, and the current EFL-containing species may
      have secondarily lost their EF-1alpha genes.

PMID- 21071192
TI  - An automated diagnostic system of polycystic ovary syndrome based on object
      growing.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that
      seriously affects women's health. The disorder is characterized by the formation
      of many follicles in the ovary. Currently the predominant diagnosis is to
      manually count the number of follicles, which may lead to inter-observer and
      intra-observer variability and low efficiency. A computer-aided PCOS diagnostic
      system may overcome these problems. However the methods reported in recently
      published literature are not very effective and often need human interaction. To
      overcome these problems, we propose an automated PCOS diagnostic system based on
      ultrasound images. METHODS AND MATERIALS: The proposed system consists of two
      major functional blocks: preprocessing phase and follicle identification based on
      object growing. In the preprocessing phase, speckle noise in the input image is
      removed by an adaptive morphological filter, then contours of objects are
      extracted using an enhanced labeled watershed algorithm, and finally the region
      of interest is automatically selected. The object growing algorithm for follicle
      identification first computes a cost map to distinguish between the ovary and its
      external region and assigns each object a cost function based on the cost map.
      The object growing algorithm initially selects several objects that are likely to
      be follicles with very high probabilities and dynamically update the set of
      possible follicles based on their cost functions. The proposed method was applied
      to 31 real PCOS ultrasound images obtained from patients and its performance was
      compared with those of three other methods, including level set method, boundary
      vector field (BVF) method and the fuzzy support vector machine (FSVM) classifier.
      RESULTS: Based on the judgment of subject matter experts, the proposed diagnostic
      system achieved 89.4% recognition rate (RR) and 7.45% misidentification rate (MR)
      while the RR and MR of the level set method, the BVF method and the FSVM
      classifier are around 65.3% and 2.11%, 76.1% and 4.53%, and 84.0% and 16.3%,
      respectively. The proposed diagnostic system also achieved better performance
      than those reported in recently published literature. CONCLUSION: The paper
      proposed an automated diagnostic system for the PCOS using ultrasound images,
      which consists of two major functional blocks: preprocessing phase and follicle
      identification based on object growing. Experimental results showed that the
      proposed system is very effective in follicle identification for PCOS diagnosis.

PMID- 21071193
TI  - Allergy and hypersensitivity.

PMID- 21071194
TI  - IL-33 family members and asthma - bridging innate and adaptive immune responses.
AB  - The discovery of IL-33 as the ligand for the orphan Th2 associated receptor ST2
      has uncovered a whole range of different avenues for this pathway. Although the
      extracellular functions of ST2 as a marker for Th2 cell and mast cell activity
      were well defined, the complexities of IL-33 regulation, nuclear function and
      secretion are only just being realised. The well documented expression pattern of
      ST2 has identified a role for the IL-33/ST2 axis in the classical Th2 cell and
      mast cell driven pathogenesis of asthma and anaphylaxis. However, the induction
      of IL-33 expression by environmental or endogenous triggers now suggests a wider
      role for the pathway during infection, inflammation and tissue damage.

PMID- 21071196
TI  - Structural organization of the Golgi apparatus.
AB  - The Golgi apparatus is a universal feature of eukaryotes, carrying out the key
      functions of processing, sorting and trafficking of newly synthesized membrane
      and secretory proteins. The Golgi apparatus has a clearly defined structure,
      comprising stacks of flattened cisternal membranes that in vertebrates are
      connected to form a ribbon. How this structure is maintained and how it relates
      to the functions of the Golgi apparatus has long been an area of interest. In
      this review I describe recent progress in the identification and characterization
      of the molecular machinery that together help generate the characteristic
      organization of this organelle.

PMID- 21071195
TI  - Role of autophagy in the host response to microbial infection and potential for
      therapy.
AB  - There is compelling evidence demonstrating a key role for autophagy in host
      defense against microbial infections. Induction and regulation of autophagy
      involves complex pathways including signaling molecules that have widespread
      roles in cell biological functions. For example, inhibiting mTOR by rapamycin,
      the most widely used chemical approach to induce autophagy, can also result in
      immunosupression. Nevertheless, advances in our understanding of autophagy
      provide a new opportunity to modulate host cellular responses as a potential
      therapeutic strategy to combat microbial infections in humans.

PMID- 21071197
TI  - Percolation and batch leaching tests to assess release of inorganic pollutants
      from municipal solid waste incinerator residues.
AB  - In this study, percolation and batch leaching tests were considered in order to
      characterize the behaviour of air pollution control (APC) residues produced in a
      municipal solid waste incinerator (MSWI) as a function of the liquid to solid
      ratio (L/S). This waste is hazardous, and taking into account their physical and
      chemical properties, leaching of contaminants into the environment is the main
      concern. In our work the leaching behaviour of toxic heavy metals (Pb, Zn, Cr, Ni
      and Cu) and inorganics associated with soluble salts (Na, K, Ca and Cl) was
      addressed. Although pH of the leaching solution is the most important variable,
      L/S may also play an important role in leaching processes. In our work, results
      from column and batch tests were compared in terms of concentration (mg/L) and
      releasing (mg/kg). The APC residues revealed to be hazardous according to both
      tests, and both Pb and Cl(-) far exceeded the regulatory thresholds. The material
      exhibits high solubility, and when the liquid to solid ratio was high, more than
      50% can be solubilised. The patterns of release may be in some cases availability
      or solubility controlled, and the former was easier to identify. When the results
      from column and batch experiments were compared by representing the cumulative
      released amounts (in mg/kg) as a function of L/S, both curves match for Zn, Ni,
      Cu, K, Na, Cl and Ca, but for Cr and Pb a significant difference was observed. In
      fact, the column experiments revealed that under percolation conditions it should
      be expected slow releasing of Pb along time. From this study, it can be concluded
      that the released amounts obtained in batch experiments for a certain L/S should
      be considered as the worst case for medium term. Some simple models proposed on
      the literature and based on local equilibrium assumption showed good fitting to
      experimental data for soluble species (non-reactive solutes).

PMID- 21071198
TI  - Response surface analysis of the water: feed ratio influences on hydrothermal
      recovery from biomass.
AB  - Response surface methodology was employed to analyze the interaction between the
      water:feed ratio (2.0-9.0), reaction temperature (180-280 degrees C) and
      retention time (0-60 min) on hydrothermal conversion of lawn grass clippings as a
      model biomass. Solid residues and the liquid pH decreased, while the water
      soluble organic fraction increased with greater water:feed ratios. Greater water
      content resulted in a higher yield of reducing sugars, proteins, and amino acids.
      This was attributed to improved mass transport properties in the subcritically
      heated water. Response surface analysis was used to describe the interaction of
      the water:feed ratio, temperature and retention time with regards to the yields
      of reducing sugars, proteins, and amino acids. The highest yields of both
      reducing sugars and amino acids were obtained with a water:feed ratio of 5.5 at
      230 degrees C reaction temperature and 30 min retention time; highest yield of
      protein was obtained with a water:feed ratio of 9.0 at 230 degrees C and 0 min
      retention time. Moreover, fitted quadratic polynomial, fitted 2FI polynomial and
      quadratic polynomial were established via ANOVA to describe the effects of
      temperature, retention time and water:feed ratio on the yield of reducing sugars,
      proteins, and amino acids.

PMID- 21071199
TI  - Effects of various fatty acid amendments on a microbial digester community in
      batch culture.
AB  - Since biogas production is becoming increasingly important the understanding of
      anaerobic digestion processes is fundamental. However, large-scale digesters
      often lack online sensor equipment to monitor key parameters. Furthermore the
      possibility to selectively change fermenting parameter settings in order to
      investigate methane output or microbial changes is limited. In the present study
      we examined the possibility to investigate the microbial community of a large
      scale (750,000 L) digester within a laboratory small-scale approach. We studied
      the short-term response of the downscaled communities on various fatty acids and
      its effects on gas production and compared it with data from the original
      digester sludge. Even high loads of formic acid led to distinct methane
      formation, whereas high concentrations of other acids (acetic, butyric, propionic
      acid) caused a marked inhibition of methanogenesis coupled with an increase in
      hydrogen concentration. Molecular microbial techniques (DGGE/quantitative real
      time-PCR) were used to monitor the microbial community changes which were related
      to data from GC and HPLC analysis. DGGE band patterns showed that the same
      microorganisms which were already dominant in the original digester re
      established again in the lab-scale experiment. Very few microorganisms dominated
      the whole fermenting process and species diversity was not easily influenced by
      moderate varying fatty acid amendments--Methanoculleus thermophilus being the
      most abundant species throughout the variants. MCR-copy number determined via
      quantitative real-time-PCR--turned out to be a reliable parameter for
      quantification of methanogens, even in a very complex matrix like fermenter
      sludge. Generally the downscaled batch approach was shown to be appropriate to
      investigate microbial communities from large-scale digesters.

PMID- 21071200
TI  - Studying transcriptional interactions in single cells at sufficient resolution.
AB  - Our ability to dissect and understand the principles of gene regulatory circuits
      is partly limited by the resolution of our experimental assays. In this brief
      review, we discuss aspects of gene expression in microbial organisms apparent
      only when increasing the experimental resolution from populations to single cells
      and sub-cellular structures, from snap-shots to high-speed time-lapse movies and
      from molecular ensembles to single molecules.

PMID- 21071201
TI  - Engineering microbes to produce biofuels.
AB  - The current biofuels landscape is chaotic. It is controlled by the rules imposed
      by economic forces and driven by the necessity of finding new sources of energy,
      particularly motor fuels. The need is bringing forth great creativity in
      uncovering new candidate fuel molecules that can be made via metabolic
      engineering. These next generation fuels include long-chain alcohols, terpenoid
      hydrocarbons, and diesel-length alkanes. Renewable fuels contain carbon derived
      from carbon dioxide. The carbon dioxide is derived directly by a photosynthetic
      fuel-producing organism(s) or via intermediary biomass polymers that were
      previously derived from carbon dioxide. To use the latter economically, biomass
      depolymerization processes must improve and this is a very active area of
      research. There are competitive approaches with some groups using enzyme based
      methods and others using chemical catalysts. With the former, feedstock and end
      product toxicity loom as major problems. Advances chiefly rest on the ability to
      manipulate biological systems. Computational and modular construction approaches
      are key. For example, novel metabolic networks have been constructed to make long
      chain alcohols and hydrocarbons that have superior fuel properties over ethanol.
      A particularly exciting approach is to implement a direct utilization of solar
      energy to make a usable fuel. A number of approaches use the components of
      current biological systems, but re-engineer them for more direct, efficient
      production of fuels.

PMID- 21071202
TI  - The emerging role for bacteria in lignin degradation and bio-product formation.
AB  - The microbial degradation of lignin has been well studied in white-rot and brown
      rot fungi, but is much less well studied in bacteria. Recent published work
      suggests that a range of soil bacteria, often aromatic-degrading bacteria, are
      able to break down lignin. The enzymology of bacterial lignin breakdown is
      currently not well understood, but extracellular peroxidase and laccase enzymes
      appear to be involved. There are also reports of aromatic-degrading bacteria
      isolated from termite guts, though there are conflicting reports on the ability
      of termite gut micro-organisms to break down lignin. If biocatalytic routes for
      lignin breakdown could be developed, then lignin represents a potentially rich
      source of renewable aromatic chemicals.

PMID- 21071203
TI  - Ubiquitin networks in cancer.
AB  - Conjugation of ubiquitin to cellular proteins has emerged as a post-translational
      modification, which affects major cellular processes, including cell cycle,
      proliferation and apoptosis. The ubiquitin-mediated signaling is frequently
      altered in cancer cells, with several tumor suppressors and oncogenes
      representing enzymes of the ubiquitin conjugation and deconjugation pathways.
      Recently, ubiquitination has been involved into selective degradation of both
      proteins and mitochondria by autophagy. Studying this novel role of ubiquitin can
      shed light on autophagy as a tumor suppressor mechanism as well as provide
      insights into the role of autophagy in survival of tumor cells, thus aiding the
      design of better cancer therapies.

PMID- 21071204
TI  - Neurobiology of behavior.

PMID- 21071206
TI  - From metals to radicals to light to loops: regulating complex reactions.

PMID- 21071205
TI  - Protein binding specificity versus promiscuity.
AB  - Interactions between macromolecules in general, and between proteins in
      particular, are essential for any life process. Examples include transfer of
      information, inhibition or activation of function, molecular recognition as in
      the immune system, assembly of macromolecular structures and molecular machines,
      and more. Proteins interact with affinities ranging from millimolar to femtomolar
      and, because affinity determines the concentration required to obtain 50%
      binding, the amount of different complexes formed is very much related to local
      concentrations. Although the concentration of a specific binding partner is
      usually quite low in the cell (nanomolar to micromolar), the total concentration
      of other macromolecules is very high, allowing weak and non-specific interactions
      to play important roles. In this review we address the question of binding
      specificity, that is, how do some proteins maintain monogamous relations while
      others are clearly polygamous. We examine recent work that addresses the
      molecular and structural basis for specificity versus promiscuity. We show
      through examples how multiple solutions exist to achieve binding via similar
      interfaces and how protein specificity can be tuned using both positive and
      negative selection (specificity by demand). Binding of a protein to numerous
      partners can be promoted through variation in which residues are used for
      binding, conformational plasticity and/or post-translational modification.
      Natively unstructured regions represent the extreme case in which structure is
      obtained only upon binding. Many natively unstructured proteins serve as hubs in
      protein-protein interaction networks and such promiscuity can be of functional
      importance in biology.

PMID- 21071207
TI  - Spinal metastasis of endometrial stromal sarcoma: clinicopathological features
      and management.
AB  - BACKGROUND: Endometrial Stromal Sarcoma (ESS) is a rare uterine malignancy which
      often metastasizes several years after initial diagnosis. Thoracic spine is a
      rare ESS metastatic site and its proper management is still not a consensus. We
      discuss the histopathological features and the management strategies through an
      illustrative case of a 77 year-old woman with metastasis to the thoracic spine 13
      years after total hysterectomy for ESS. METHODS: Review of the literature and
      identification of 5 patients, including our present case, with ESS involving the
      spinal cord. We discuss the outcomes achieved after each therapy. In our case,
      the patient presented a mass involving the thoracic spinal canal constricting the
      spinal cord at T7 level. A two-level decompression laminectomy was performed and
      the lesion was partially excised. RESULTS: The histopathological along with the
      immunohistochemical profile mitotic rate indicated the endometrial stromal cells
      origin of the tumor, confirming the diagnosis of a low-grade ESS metastasis. The
      patient was managed with surgery in combination with postoperative radiation
      therapy. CONCLUSIONS: The small number of published cases precludes definitive
      conclusions regarding standard management. However, it seems that treatment of
      metastatic ESS to the spine matches the same general concepts of spine
      metastasis, namely surgery followed by radiation therapy, due to clinical
      improvement and long-term disease control of the reported cases. Hormonal therapy
      may be considered in recurrent disease with strong expression of estrogen and
      progesterone receptors. However, these findings need confirmation in larger
      studies.

PMID- 21071208
TI  - The national bowel cancer audit project: the impact of organisational structure
      on outcome in operative bowel cancer within the United Kingdom.
AB  - OBJECTIVES: To investigate the relationship between organisational structure,
      process and surgical outcomes for bowel cancer surgery. METHODS: An e-survey was
      sent to the members of the Association of Coloproctology of Great Britain and
      Ireland to determine the organisational structure of their Trusts. Responses were
      combined with the National Bowel Cancer Audit (NBOCAP) data. Items investigated
      included; number of consultants, nurse specialists, volume of cases and intensive
      care facilities. Main outcome measures included: 30-day risk-adjusted mortality,
      length of stay (LOS), lymph node yield and circumferential margin involvement
      (CRM). RESULTS: One hundred and seventeen Trusts responded (65.8%), matched to
      7666 patient episodes (NBOCAP data) from 54 (62.8%)Trusts who submitted data to
      the audit. Trusts treating <190 cases/annum (p > 0.001), <4 colorectal
      consultants (p > 0.001), <4 HDU beds (p > 0001) and <8 ITU beds (p > 0001) were
      more likely to have a 30-day-risk-adjusted mortality twice that of the national
      mean. Sixty five percent (n = 1603) of Trusts treating >= 190 cases/annum
      harvested >= 12 lymph nodes vs. 58.3% (n = 1435) in Trusts <190 cases/annum (p <
      0.001). Trusts with >= 2 pathologists with an interest in bowel cancer harvested
      >= 12 lymph nodes more frequently (p=<0.001) and were more likely to identify
      extramural vascular invasion in the specimen (p = 0.015). Negative CRM was
      achieved in 81.4% (n = 81.4) of patients in Trusts treating >= 190 cases vs.
      66.5% (n = 569) in Trusts<190 cases/annum (p < 0.001). Trusts offering fast track
      discharge were more likely to have a LOS < 15 days (p = 0.006). Surgeons treating
      <= 35 cases/annum had increased major post-operative complications (<35 cases =
      70.2% vs. >= 35 cases = 21.9%; p < 0.001), however 30 day risk adjusted mortality
      was not increased in surgeons treating <35 cases/annum. CONCLUSIONS: This study
      shows that the organisational infrastructure of hospitals appears to have as
      great an impact on patient outcomes as the volume of cases performed by hospital
      Trusts.

PMID- 21071209
TI  - Objective assessment, selection, and certification in surgery.
AB  - Historically, surgical competence has been evaluated subjectively. Fundamental
      changes in surgical technology and training have focused attention on the use of
      objective measurement of performance to improve patient safety and reduce errors.
      Surgical performance can be measured using a variety of tools, both in the
      clinical and simulated environments. Objective assessments can play a role in
      training by improving the evaluation and feedback. At the end of training or when
      a new skill is acquired, objective assessments may be used to ensure that a
      proficiency level has been reached and potentially as a condition for independent
      practice. When assessments are used for high-stakes evaluations like
      certification, they must be demonstrably reliable and valid. The definition of
      assessment, and the necessary components of a valid instrument, will be
      summarized. An overview of practical applications of objective assessment as it
      applies to training, selection, and certification of surgeons will be presented.

PMID- 21071210
TI  - Incremental energy supply for microalgae culture in a photobioreactor.
AB  - A model was developed for any PBR, based on mixing requirement per unit of
      biomass production rather than constant amount of mixing energy. The model
      assumes constant biomass concentration throughout the culture time which means
      the volume of the culture would increase over time; the mixing energy will also
      increase over time according to the volume of the culture. Such incremental
      energy supply (IES) consumes much less energy compared to constant energy supply
      (CES); higher the culture time in the PBR, more is the savings in the IES
      compared to CES. In addition to mixing energy, light energy can also be applied
      using IES scheme. The model was validated with the algae Nannochloropsis sp.; 44%
      of the energy input of CES was saved by adopting IES with equal biomass
      productivities for a culture period of 60 h.

PMID- 21071211
TI  - Effects of CaCl2 on viscosity of culture broth, and on activities of enzymes
      around the 2-oxoglutarate branch, in Bacillus subtilis CGMCC 2108 producing poly
      (gamma-glutamic acid).
AB  - CaCl(2) was used as a novel additive to enhance poly-(gamma-glutamic acid) (gamma
      PGA) production by Bacillus subtilis strain CGMCC 2108. Addition of CaCl(2) to
      medium effectively reduced viscosity of culture broth, and increased consumption
      of extracellular glutamate by 11.4%, leading to gamma-PGA yield of 9.07 g/l,
      compared to 7.88 g/l in control. CaCl(2) also increased activities of three key
      enzymes around the crucial 2-oxoglutarate branch of the gamma-PGA biosynthesis
      pathway: isocitrate dehydrogenase (ICDH), glutamate dehydrogenase (GDH), and 2
      oxoglutarate dehydrogenase complex (ODHC). In particular, GDH activity was
      increased more than 8-fold, indicating that more 2-oxoglutarate was directed to
      synthesis of glutamate, the substrate of gamma-PGA. Interestingly, the molecular
      weight of gamma-PGA remained constant regardless of CaCl(2) addition.

PMID- 21071212
TI  - The effect of metal salts on the decomposition of sweet sorghum bagasse in flow
      through liquid hot water.
AB  - The impact of the metal salts NaCl, KCl, CaCl(2), MgCl(2), FeCl(3), FeCl(2), and
      CuCl(2), particularly the latter, on the decomposition of hemicellulose and
      lignin from sweet sorghum bagasse in liquid hot water pretreatment processing was
      studied in an attempt to enhance the recovery of sugars. Transition metal
      chlorides significantly enhanced the hemicellulose removal compared to the
      alkaline earth metal chlorides and alkaline metal chlorides, contributing to the
      formation of a saccharide-metal cation intermediate complex. FeCl(2) greatly
      increased xylose degradation and about 60% xylan was converted into non
      saccharide products. In contrast, an excellent total and monomeric xylose
      recovery was obtained after the CuCl(2) pretreatment. Most of the lignin was
      deposited on the surface of the residual solid with droplet morphologies after
      this pretreatment, and about 20% was degraded into monomeric products. The total
      recovery of sugars from sweet sorghum bagasse with 0.1% CuCl(2) solution
      pretreatment and 48 h enzymatic digestibility, reached 90.4%, which is superior
      to the recovery using hot water pretreatment only.

PMID- 21071213
TI  - Sulfate-reducing bacteria in a denitrification reactor packed with wood as a
      carbon source.
AB  - A denitrification reactor packed with wood as a carbon source was operated using
      synthetic inorganic wastewater. The maximum denitrification rate was 62.4 g
      NO(3)(-)/m(3)/day at HRT of 24 h. The nitrate removal continued after 1500 days.
      The denitrification efficiency was assumed to enhance sulfur denitrification via
      wood degradation by sulfate reduction. The achieved sulfate reduction rate was
      468 mg-SO(4)(2-)/kg-dry weight wood/day after 419 days of operation. The sulfate
      reduction rate in the deep-layer biofilm inside the wood was higher than that in
      the total biofilm inside the wood. The sulfate-reducing bacteria segregated
      inside the wood. This study suggested that Desulfobulbus spp. and
      Desulfomicrobium spp. grown in the deep-layer degraded the wood incompletely, and
      the produced organic acids were utilized by the heterotrophic denitrifying
      bacteria, Desulfobacter spp. and Desulfonema spp., grown in the surface layer,
      and that these surface bacteria complete the degradation of the organic acids
      from the wood.

PMID- 21071214
TI  - Purification and characterization of a novel fibrinolytic enzyme from fruiting
      bodies of Korean Cordyceps militaris.
AB  - A fibrinolytic enzyme has been purified from the fruiting bodies of Korean
      Cordyceps militaris. The molecular mass of the enzyme was estimated to be 34 kDa
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fibrin
      zymography, and gel filtration chromatography. The 15 amino acid residues of the
      N-terminal sequence of the enzyme were APVEQCDAPVGLARL, which is dissimilar to
      those of fibrinolytic enzymes from other mushrooms. Optimal pH and temperature
      values of the enzyme were 7.0 and 40 degrees C, respectively. The enzyme activity
      was completely inhibited by phenylmethylsulfonyl fluoride (PMSF), TPCK, 1,10
      phenanthroline, Cu(2+), and Ba(2+). It was also significantly inhibited by
      aprotinin, EDTA, and EGTA. The enzyme showed a higher specificity for a synthetic
      substrate, N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, exhibiting that it is a
      chymotrypsin-like serine metalloprotease. The enzyme preferentially hydrolyzed
      the fibrinogen Aalpha-, followed by the Bbeta-chains and the gamma-chain. The
      alpha, beta, and gamma-gamma chains of fibrin were also degraded by the enzyme.

PMID- 21071215
TI  - A rapid and sensitive method for the evaluation of cereal grains in bioethanol
      production using near infrared reflectance spectroscopy.
AB  - The potential of near infrared spectroscopy (NIRS) for determining fermentable
      substance and also ethanol yield in wheat, rye and triticale grains as a
      feedstock for fuel ethanol production was investigated. The total sample set
      contained 480 samples of 10 types of wheat, 24 types of triticale and 6 types of
      rye, which were grown on 10 locations in Germany from 2006 to 2008. Samples were
      scanned by NIRS as whole or ground grains, and their reference values regressed
      against different spectral transformations by partial least squares regression
      (PLS-1). Ground grains were scanned on a dispersive NIR-Spectrometer. Whole
      grains were scanned on a diode array NIR-Spectrometer. Principal Component
      Analysis (PCA) revealed that samples could be classified by crop season, growth
      location and species. It is shown that near infrared spectroscopy is an
      appropriate and useful tool for prediction of biofuel yield for both industry and
      research.

PMID- 21071216
TI  - Fermentative hydrogen production from fresh leachate in batch and continuous
      bioreactors.
AB  - This research for the first time investigated hydrogen production from the fresh
      leachate originated from municipal solid wastes. We found that fermentation of
      the leachate generated H(2) and was very much enhanced in the presence of extra
      phosphate in the batch reactor. The continuous expanded granular sludge bed
      (EGSB) reactor started to generate H(2) at day 20 and continued to 176 days with
      120 mg/l of extra phosphate present. The highest chemical oxygen demand (COD)
      removal efficiency (66.9%) was achieved at liquid up-flow velocity of 3.7 m/h and
      hydraulic retention time of 12h. Under proposed optimal operation conditions, the
      mean H(2) production rate reached up to 2155 ml/(l day). We also found that over
      80% liquid metabolites were acetic acid and ethanol, suggesting the ethanol-type
      fermentation was dominant in the bioreactor. These findings indicate that the
      fresh leachate can be used as the source for continuous hydrogen production.

PMID- 21071217
TI  - The methane yield of digestate: effect of organic loading rate, hydraulic
      retention time, and plant feeding.
AB  - In biogas plants, huge volumes of digestate are produced daily and stored in
      uncovered tanks, which leak methane into the atmosphere and cause negative
      environmental impacts. To better understand the effect that different operating
      parameters of anaerobic digestion plants have on digestate residual methane
      yield, four digestate samples collected from plants with very different
      operations were analysed in batch reactors. Their methane yields were very
      heterogeneous and varied between 2.88 and 37.63 NL/kgVS. The methane yield was
      shown to be highly influenced by the A.D. plant Organic Loading Rate and by
      feedstock quality; hydraulic retention time had only limited effects.

PMID- 21071218
TI  - Cholesterol-based alpha-phenyl-N-tert-butyl nitrone derivatives as antioxidants
      against light-induced retinal degeneration.
AB  - Two cholesterol-based alpha-phenyl-N-tert-butyl nitrone derivatives were
      synthesized as antioxidants against light-induced retinal degeneration. Whereas
      nitrone 10 significantly protected retina against bright fluorescent light
      exposure when injected into the vitreous at 1 mM, no protection was observed with
      nitrone 6. The parent compound alpha-phenyl-N-tert-butyl nitrone also exhibited
      protective activity at 9 mM but not at 1 mM. This suggests that nitrone 10 may be
      a candidate for the treatment of retinal diseases.

PMID- 21071219
TI  - Synthesis, crystal structure, DNA-binding and cytotoxicity in vitro of novel cis
      Pt(II) and trans-Pd(II) pyridine carboxamide complexes.
AB  - In an attempt to establish fundamental structure-activity relationships (SAR) of
      Pt/Pd-based anti-tumour compounds, we have recently designed monodentate pyridyl
      amide ligand containing central amide units which possess external metal co
      ordinating pyridyl group and internal amide functionality. It was prepared in one
      step from commercially available compounds in moderate to good yield.
      Surprisingly, treatment of K(2)[MCl(4)] [M=Pt(II), Pd(II)] with ligand N-(4
      chlorophenyl)-3-pyridinecarboxamide (L) in the same reaction condition affords
      two different hydrogen-bonded polymers: cis-[PtL(2)Cl(2)].CH(3)OH.DMF (1) and
      trans-[PdL(2)Cl(2)].2DMF (2). Fluorescence analysis indicates that the two
      complexes can bind to fish sperm DNA (FS-DNA) and gel electrophoresis assay
      demonstrates the ability of the complexes to cleave the pBR322 plasmid DNA. The
      two complexes exhibit cytotoxic specificity and significant cancer cell
      inhibitory rate. Furthermore, cytotoxicity values are higher in the case of cis
      Pt(II) complex than trans-Pd(II) complex in four different cancer cell lines.

PMID- 21071220
TI  - A facile 1,3-dipolar cycloaddition of azomethine ylides to 2-arylidene-1,3
      indanediones: synthesis of dispiro-oxindolylpyrrolothiazoles and their
      antimycobacterial evaluation.
AB  - A facile 1,3-dipolar cycloaddition of azomethine ylide generated in situ from the
      reaction of 1,3-thiazolane-4-carboxylic acid and isatin to 2-arylidene-1,3
      indanediones furnished novel dispiro-oxindolylpyrrolothiazoles regio- and stereo
      selectively in moderate to good yields (60-92%). In vitro antitubercular
      screening of 27 compounds against Mycobacterium tuberculosis H37Rv (MTB)
      disclosed that spiro[5.3']-5'-nitrooxindolespiro-[6.3"]-1H-inden-1",3"(2H)-dione
      7-(4-bromophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole has the maximum
      potency with a minimum inhibitory concentration (MIC) of 1.4 MUM against MTB,
      being 3.4 and 5.4 times more potent than ciprofloxacin and ethambutol,
      respectively.

PMID- 21071221
TI  - Synthesis and in vitro evaluation of novel coumarin-chalcone hybrids as potential
      anticancer agents.
AB  - A series of coumarin-chalcone hybrids have been synthesized and evaluated for
      their in vitro cytotoxicity against a panel of four human cancer cell lines and
      normal fibroblasts (NIH3T3). Among 21 compounds screened, three compounds (23, 25
      and 26) showed IC(50) range from 3.59 to 8.12 MUM. The most promising compound 26
      showed around 30-fold more selectivity towards C33A (cervical carcinoma) cells
      over normal fibroblast NIH3T3 cells with an IC(50) value of 3.59 MUM.

PMID- 21071222
TI  - Synthesis, antimicrobial and antioxidant evaluation of quinolines and
      bis(indolyl)methanes.
AB  - An improved and practical synthesis of substituted quinolines and
      bis(indolyl)methanes was achieved under microwave condition using Zn(OTf)(2) as
      catalyst. The synthesized compounds have been screened for antimicrobial and
      antioxidant activities.

PMID- 21071223
TI  - Design and synthesis of disubstituted thiophene and thiazole based inhibitors of
      JNK.
AB  - From high throughput screening, we discovered compound 1, the prototype for a
      series of disubstituted thiophene inhibitors of JNK which is selective towards
      closely related MAP kinases p38 and Erk2. Herein we describe the evolution of
      these compounds to a novel class of thiophene and thiazole JNK inhibitors that
      retain favorable solubility, permeability, and P-gp properties for development as
      CNS agents for treatment of neurodegeneration. Compound 61 demonstrated JNK3
      IC(50)=77 nM and retained the excellent broad kinase selectivity observed for the
      series.

PMID- 21071224
TI  - Novel insights into the use of Glowing LNA as nucleic acid detection probes-
      influence of labeling density and nucleobases.
AB  - Appropriately designed 2'-N-(pyren-1-yl)carbonyl-2'-amino-LNA (locked nucleic
      acid) display large increases in fluorescence intensity and remarkably high
      quantum yields upon hybridization with nucleic acid targets. Thermal denaturation
      and fluorescence spectroscopy studies on ONs modified with known thymine monomer
      X and novel 5-methylcytosine monomer Y provide new insights into the design
      principles and mechanism of these Glowing LNA nucleic acid detection probes.

PMID- 21071225
TI  - Trends in incidence of ductal carcinoma in situ: the effect of a population-based
      screening programme.
AB  - BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased
      substantially in the western world in recent decades. The aim of this study was
      to investigate the incidence according to grade distribution, age, and
      implementation of a population-based screening programme. METHODS: Cases of
      primary pure DCIS (n = 3167) were obtained from the Cancer Registry of Norway.
      Poisson regression was used to estimate trends in incidence. RESULTS: Age
      adjusted incidence of DCIS increased from 4 to 11 per 100, 000 women-years from
      1993 to 2007, in parallel with the implementation of screening. Higher incidence
      was observed among prevalent (IRR 3.3) and subsequent (IRR 2.8) invited women
      compared with those not invited. The proportion of DCIS among breast malignancies
      increased throughout the period, most markedly in the age range of screening.
      CONCLUSION: The increased proportion of DCIS during the study period is probably
      due to improved diagnostics resulting from the implementation of population-based
      screening.

PMID- 21071227
TI  - When the family member is a nurse: the role and needs of nurse family members
      during critical illness of a loved one.
AB  - OBJECTIVES: The aim of this study was to explore the experience of being a nurse
      family member of a relative hospitalised for a critical illness. This paper will
      describe how nurse family members viewed the challenges of the illness experience
      and the strategies used to manage the challenges and cope with their loved one's
      critical illness. METHODS: A qualitative approach using open-ended, focused
      exploratory interviews was used. Theoretical sampling was used to obtain a total
      of 22 participants. RESULTS: The knowledge base of the nurse filtered the
      experience for the nurse family member and their nurse role identity infused each
      component of the experience. Nurse family members identified their primary role
      as maintaining guard to protect the patient and family. To accomplish this, six
      challenges were identified: masking heightened emotional turmoil; assuming the in
      charge role; assessing and monitoring; seeking information and meaning;
      advocating; and, "letting go to assume family and self roles". Strategies to
      facilitate meeting these challenges are described. CONCLUSIONS: In order to
      provide family-centered care, the critical care nurse must recognise the unique
      needs of the "nurse family member." By empathising with the emotional experience,
      allowing the "in-charge" nurse family member to be part of the team, facilitating
      ongoing observation and monitoring by the nurse family member, seeking out and
      clarifying information for the nurse family member and partnering to advocate for
      the patient, the critical care nurse builds a relationship of trust that allows
      the nurse family member to assume their family role.

PMID- 21071228
TI  - Smaller sway size during quiet standing is associated with longer preceding time
      of motor command to body sway.
AB  - In previous studies, it was found using cross-correlation analysis that the
      modulation of the motor command to the calf muscles largely precedes body sway
      during quiet standing. The purpose of this study was to investigate whether this
      preceding time is correlated with an improved stabilization of the body. 26 young
      and 23 elderly healthy subjects were asked to stand quietly. Body sway was
      measured using a laser displacement sensor, and the electromyogram of the right
      soleus was measured as a representative of the motor command. The correlation and
      the time shift between motor command and body sway were estimated by means of
      cross-correlation analysis. We found that sway size was correlated with the
      identified time shift: that is, a smaller sway size was associated with a longer
      preceding time. The obtained results suggest that a control strategy generating a
      larger preceding time can stabilize the body more effectively. This result was
      found in both the young and elderly, suggesting that the particular control
      aspect associated with the time shift is a common feature in both age groups.

PMID- 21071226
TI  - Metastasis: tumor cells becoming MENAcing.
AB  - During breast cancer metastasis cells emigrate from the primary tumor to the
      bloodstream, and this carries them to distant sites where they infiltrate and
      sometimes form metastases within target organs. These cells must penetrate the
      dense extracellular matrix comprising the basement membrane of the mammary
      duct/acinus and migrate toward blood and lymphatic vessels, processes that
      mammary tumor cells execute primarily using epidermal growth factor (EGF)
      dependent protrusive and migratory activity. Here, we focus on how the actin
      regulatory protein Mena affects EGF-elicited movement, invasion and metastasis.
      Recent findings indicate that, in invasive migratory tumor cells, Mena isoforms
      that endow heightened sensitivity to EGF and increased protrusive and migratory
      abilities are upregulated, whereas other isoforms are selectively downregulated.
      This change in Mena isoform expression enables tumor cells to invade in response
      to otherwise benign EGF stimulus levels and could offer an opportunity to
      identify metastatic risk in patients.

PMID- 21071229
TI  - A species concept for bacteria based on adaptive divergence.
AB  - Bacterial strains are currently grouped into species based on overall genomic
      similarity and sharing of phenotypes deemed ecologically important. Many believe
      this polyphasic taxonomy is in need of revision because it lacks grounding in
      evolutionary theory, and boundaries between species are arbitrary. Recent
      taxonomy efforts using multilocus sequence typing (MLST) data are based on the
      identification of distinct phylogenetic clusters. However, these approaches face
      the problem of deciding the phylogenetic level at which clusters are
      representative of evolutionary or taxonomically distinct units. In this review, I
      propose classifying two phylogenetic clusters as separate species only when they
      have statistically significantly diverged as a result of adaptive evolution. More
      than a method for classification, the concept of adaptive divergence can be used
      in a 'reverse ecology' approach to identify lineages that are in the process of
      speciation or genes involved in initial adaptive divergence.

PMID- 21071230
TI  - Synthesis and biological evaluation of new camptothecin derivatives obtained by
      modification of position 20.
AB  - The preparation and biological evaluation of a novel series of dimeric
      camptothecin derivatives are described. All the new compounds showed a
      significant ability to inhibit human tumor cell growth with IC(50) values ranging
      from 0.03 to 12.2 MUM. The interference with the activity of the nuclear enzymes
      topoisomerases has been demonstrated, highlighting the poison effect of one of
      the obtained byproducts toward topoisomerase I. A moderate antiangiogenic
      activity has been demonstrated for one of the obtained compounds. Moreover, the
      effects of four new compounds on caspases activity and ROS generation have been
      studied on transgenic mouse cell.

PMID- 21071231
TI  - 2-aminohydroxamic acid derivatives as inhibitors of Bacillus cereus
      phosphatidylcholine preferred phospholipase C PC-PLC(Bc).
AB  - Phosphatidylcholine preferring phospholipase C (PC-PLC) is an important enzyme
      that plays a key role in a variety of cellular events and lipid homoeostases.
      Bacillus cereus phospholipase C (PC-PLC(Bc)) has antigenic similarity with the
      elusive mammalian PC-PLC, which has not thus far been isolated and purified.
      Therefore the discovery of inhibitors of PC-PLC(Bc) is of current interest. Here,
      we describe the synthesis and biological evaluation of a new type of compounds
      inhibiting PC-PLC(Bc). These compounds have been designed by evolution of
      previously described 2-aminohydroxamic acid PC-PLC(Bc) inhibitors that block the
      enzyme by coordination of the zinc active site atoms present in PC-PLC(Bc)
      [Gonzalez-Roura, A.; Navarro, I.; Delgado, A.; Llebaria, A.; Casas, J. Angew.
      Chem. Int. Ed.2004, 43, 862]. The new compounds maintain the zinc coordinating
      groups and possess an extra trimethylammonium function, linked to the
      hydroxyamide nitrogen by an alkyl chain, which is expected to mimic the
      trimethylammonium group of the phosphatidylcholine PC-PLC(Bc) substrates. Some of
      the compounds described inhibit the enzyme with IC(50)'s in the low micromolar
      range. Unexpectedly, the most potent inhibitors found are those that possess a
      trimethylammonium group but have chemically blocked the zinc coordinating
      functionalities. The results obtained suggest that PC-PLC(Bc) inhibition is not
      due to the interaction of compounds with the phospholipase catalytic zinc atoms,
      but rather results from the inhibitor cationic group recognition by the PC
      PLC(Bc) amino acids involved in choline lipid binding.

PMID- 21071232
TI  - Angiotensin II receptor type 1 (AT1) selective nonpeptidic antagonists--a
      perspective.
AB  - Hypertension is a major risk factor for human morbidity and mortality through its
      effects on target organs like heart, brain and kidneys. More intensive treatment
      for the effective control of blood pressure significantly reduces the morbidity
      and mortality. The renin angiotensin system (RAS) is a coordinated hormonal
      cascade of major clinical importance in the regulation of blood pressure. The
      principal effector peptide of RAS is angiotensin II, which acts by binding to one
      of the two major angiotensin II receptors AT(1) and AT(2). Angiotensin II through
      AT(1) receptor mediates vast majority of biologically detrimental actions.
      Nonpeptidic angiotensin II (AT(1)) antagonists are the most specific means to
      block the renin angiotensin enzymatic cascade available presently. Majority of
      AT(1) antagonists are based on modifications of losartan structure, the first
      clinically used AT(1) antagonist. In this review, a comprehensive presentation of
      the literature on AT(1) receptor antagonists has been given.

PMID- 21071233
TI  - A novel PET marker for in vivo quantification of myelination.
AB  - C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and
      evaluated as a novel radiotracer for in vivo microPET imaging of myelination.
      [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct)
      value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in
      myelinated regions such as corpus callosum and striatum. The corpus callosum
      region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse
      brain than in the wild-type mouse brain, a pattern that was also consistently
      observed in Black-Gold or MBP antibody staining. Ex vivo autoradiography
      demonstrated that [(11)C]MeDAS readily entered the mouse brain and selectively
      labeled myelinated regions with high specificity. Biodistribution studies showed
      abundant initial brain uptake of [(11)C]MeDAS with 2.56% injected dose/whole
      brain at 5 min post injection and prolonged retention in the brain with 1.37%
      injected dose/whole brain at 60 min post injection. An in vivo pharmacokinetic
      profile of [(11)C]MeDAS was quantitatively analyzed through a microPET study in
      an Plp-Akt-DD hypermyelinated mouse model. MicroPET studies showed that
      [(11)C]MeDAS exhibited a pharmacokinetic profile that readily correlates the
      radioactivity concentration to the level of myelination in the brain. These
      studies suggest that MeDAS is a sensitive myelin probe that provides a direct
      means to detect myelin changes in the brain. Thus, it can be used as a myelin
      imaging marker to monitor myelin pathology in vivo.

PMID- 21071234
TI  - Characterization of the fast neutron irradiation facility of the Portuguese
      Research Reactor after core conversion.
AB  - The fast neutron irradiation facility of the Portuguese Research Reactor was
      characterized after the reduction in uranium enrichment and rearrangement of the
      core configuration. In this work we report on the determination of the hardness
      parameter and the 1MeV equivalent neutron flux along the facility, in the new
      irradiation conditions, following ASTM E722 standard.

PMID- 21071235
TI  - Effects of the composition of standard reference material on the accuracy of
      determinations of 210Pb and 137Cs in soils with gamma spectrometry.
AB  - The effect of the composition of the used standard reference material (SRM) on
      results of determination of fallout radionuclides in soil samples was studied.
      Using five soil types as SRMs, we measured the specific activity of (210)Pb and
      (137)Cs in six target samples of Chestnut soil. It was observed that the
      determination of the (210)Pb activity in the samples depended on the chemical
      composition of SRMs used to create the efficiency curves. Thus, using SRMs
      similar in chemical composition to the target samples should improve accuracy in
      the determination of (210)Pb in environmental samples.

PMID- 21071236
TI  - Acyl-ACP thioesterases from macadamia (Macadamia tetraphylla) nuts: cloning,
      characterization and their impact on oil composition.
AB  - The mechanisms by which macadamia nuts accumulate the unusual palmitoleic and
      asclepic acyl moieties, which constitute up to 20% of the fatty acids in some
      varieties, are still unknown. Acyl-acyl carrier protein (ACP) thioesterases (EC
      3.1.2.14) are intraplastidial enzymes that terminate the synthesis of fatty acids
      in plants and that facilitate the export of the acyl moieties to the endoplasmic
      reticulum where they can be used in the production of glycerolipids. Here, we
      have investigated the possible role of acyl-ACP thioesterase activity in the
      composition of macadamia kernel oil. Accordingly, two acyl-ACP thioesterases were
      cloned from developing macadamia kernels, one of the FatA type and the other of
      the FatB type. These enzymes were heterologously expressed in Escherichia coli,
      and the recombinant thioesterases were purified, characterized kinetically and
      assayed with a variety of substrates, demonstrating the high specificity of
      macadamia FatA towards 16:1-ACP. Acyl-ACP thioesterase activity was also
      characterized in crude extracts from two different varieties of macadamia, Cate
      and Beaumont, which accumulate different amounts of n-7 fatty acids. The impact
      of acyl-ACP thioesterase activities on the oil composition of these kernels is
      discussed in the light of these results.

PMID- 21071237
TI  - Neurofibromatosis type 1 associated with bilateral central giant cell granuloma
      of the mandible.
AB  - Neurofibromatosis type 1, or von Recklinghausen disease, is one of the most
      common hereditary neurocutaneous disorders in humans. Clinically,
      Neurofibromatosis type 1 is characterized by cafe-au-lait spots, freckling, skin
      neurofibroma, plexiform neurofibroma, bony defects, Lisch nodules and tumors of
      the central nervous system. Central giant cell granuloma is a benign central
      lesion of bone, primarily involving the jaws, of variably aggressive nature
      characterized by aggregates of multinucleated giant cells in a background of
      cellular vascular fibrous connective tissue and spindle-shaped mononuclear
      stromal cells. The association between neurofibromatosis and central giant cell
      granuloma has been reported in the literature. A case of mandibular bilateral
      central giant cell granuloma in a patient with Neurofibromatosis type 1 was
      conservatively but successfully treated by adequate surgical curettage of
      mandibular bone lesions.

PMID- 21071238
TI  - Marginal resection for treatment of mandibular osteomyelitis associated with
      osteopetrosis: case report.
AB  - Osteopetrosis (OP) is a rare hereditary disorder characterized by a dysfunction
      of the osteoclasts that impairs bone resorption, which together with the normal
      osteoblastic activity forms intense bone sclerosis with reduction of marrow. A
      common complication that arises, most frequently, as a result of tooth extraction
      is mandibular osteomyelitis. There is no consensus on the literature about the
      treatment of this infection in an osteopetrotic patient, therefore, the purpose
      of this paper is to report a case of marginal resection for treatment of
      mandibular osteomyelitis in an osteopetrotic patient and discuss relevant
      features of this procedure.

PMID- 21071239
TI  - Right coronary thrombosis in patient supported by Jarvik 2000 left ventricular
      assist device.

PMID- 21071240
TI  - Extracorporeal membrane oxygenation as perioperative right ventricular support in
      patients with biventricular failure undergoing left ventricular assist device
      implantation.
AB  - OBJECTIVE: Left-ventricular assist device (LVAD) implantation complicated by
      early right ventricle (RV) failure has a poor prognosis. This study details our
      center's experience with veno-arterial extracorporeal membrane oxygenation (ECMO)
      as perioperative RV support in patients with preoperative biventricular failure
      undergoing LVAD implantation. METHODS: Ten patients, who underwent LVAD
      implantation, were retrospectively analyzed. Six patients were already supported
      with ECMO before LVAD implantation. In four patients, the ECMO was implanted
      before weaning from cardiopulmonary bypass. RESULTS: All patients showed reduced
      RV function with elevated right-ventricular end-diastolic diameter (RVEDD) (38 +/
      4 mm) and RV systolic pressure (48 +/- 14 mmHg). The mean pulmonary artery
      pressure (PAP) was 36 +/- 9 mmHg. Nine patients showed dilatation of the
      tricuspid annulus (>= 35 mm) with moderate tricuspid valve insufficiency and
      received tricuspid valve annuloplasty. After removal of the ECMO, none of the
      patients developed RV failure. ECMO was removed 4+/-1 days after LVAD
      implantation. Four patients expired while on LVAD support due to not-device
      related sepsis (two patients), mesenteric ischemia (one patient), and
      gastrointestinal bleeding (one patient), respectively. Overall survival was 60%.
      CONCLUSION: ECMO provided a satisfactory perioperative right-heart support in
      patients with preoperative biventricular failure undergoing LVAD implantations,
      who otherwise were better candidates for biventricular assist device. ECMO
      allowed time for the already compromised right ventricle to get attuned to the
      increasing preload, and avoids distension and RV failure.

PMID- 21071241
TI  - Visualization of commissural detachment by three-dimensional echocardiography and
      successful treatment by aortic root and commissural repair.

PMID- 21071242
TI  - Unraveling the neurophysiology of muscle fatigue.
AB  - Despite 100years of research since the seminal work of Angelo Mosso (1846-1910),
      our understanding of the interactions between the nervous system and muscle
      during the performance of fatiguing contractions remains rather rudimentary.
      Although the nervous system simply needs to provide an activation signal that
      will elicit the net muscle torque required for a prescribed action, changes in
      the number and diversity of synaptic inputs that must be integrated by the spinal
      motor neurons to accommodate the changes in the force-producing capabilities of
      the muscle fibers complicate the process of generating the requisite activation
      signal. This brief review examines two ways in which the activation signal can be
      compromised during sustained contractions and thereby contribute to the rate at
      which the muscles fatigue. These examples provide insight on the types of
      adjustments that occur in the nervous system during fatiguing contractions, but
      emphasize that much remains to be learned about the physiological processes that
      contribute to the phenomenon known as muscle fatigue.

PMID- 21071243
TI  - Electromyographic activity of selected trunk muscles in subjects with and without
      hemiparesis during therapeutic exercise.
AB  - The purpose of this study was to evaluate the trunk muscles activity of
      hemiparetic and control subjects during selected therapeutic exercises with
      surface electromyography (sEMG). The sEMG evaluation included 12 subjects
      presenting hemiparesis after having suffered a unilateral stroke and 12
      apparently healthy subjects. A 16-channel sEMG system was used; data were band
      pass filtered from 20 to 450Hz. The signal was normalized through reference
      voluntary contraction (RVC) and presented in percentage. The exercises used in
      the evaluations were trunk flexion and trunk extension. Rectus abdominis
      presented greater activation on the paretic side of the experimental group than
      on the corresponding side of the control group (P=0.035) (Cohen's d-=0.94).
      During leg elevation, the non-paretic obliquus externus abdominis showed greater
      activation than in other exercises (P=0.019) (Cohen's d-=0.75). No inter-group
      differences were found for either erectus spinae activity or contraction onset.
      Experimental group subjects showed muscle activity alterations, principally in
      the rectus abdominis, indicating the occurrence of compensatory strategies.

PMID- 21071244
TI  - Hallucinations and REM sleep behaviour disorder in Parkinson's disease: dream
      imagery intrusions and other hypotheses.
AB  - REM sleep behaviour disorder (RBD) is a REM sleep-related parasomnia which may be
      considered a "dissociated state of wakefulness and sleep", given that conflicting
      elements of REM sleep (dreaming) and of wakefulness (sustained muscle tone and
      movements) coexist during the episodes, leading to motor and behavioural
      manifestations reminiscent of an enacted dream. RBD has been reported in
      association with alpha-synucleinopathies: around a third of patients with
      Parkinson's disease (PD) have full-blown RBD. Recent data indicate that PD
      patients with RBD are more prone to hallucinations than PD patients without this
      parasomnia. However it is still not clear why RBD in PD is associated with an
      increased prevalence of VHs. Data exist which suggest that visual hallucinations
      in PD may be the result of untimely intrusions of REM visual imagery into
      wakefulness. RBD, which is characterised by a REM sleep dissociation pattern,
      might be a condition that particularly favours such intrusions. However, other
      hypotheses may be advanced. In fact, deficits in attentional, executive,
      visuoperceptual and visuospatial abilities have been documented in RBD and found
      to occur far more frequently in PD with RBD than in PD without RBD.
      Neuropsychological deficits involving visual perception and attentional processes
      are thought to play an important role in the pathophysiology of VHs. On this
      basis, RBD in PD could be viewed as a contributory risk factor for VHs.

PMID- 21071245
TI  - Chromosomal localisation and genetic variation of the SLC11A1 gene in goats
      (Capra hircus).
AB  - The solute carrier family 11 member A1 (SLC11A1) gene is associated with
      resistance to infectious diseases. Chromosomal localisation, genomic regions
      corresponding to functional domains and the genetic variability of
      microsatellites in the 3' untranslated region (3'-UTR) of this gene were
      investigated in 427 goats (Capra hircus) of six breeds. Using dual colour
      fluorescence in situ hybridisation, SLC11A1 was localised to goat chromosome 2.
      Single strand conformation polymorphism was used to screen for polymorphisms in
      SLC11A1 exons 2, 10 and 15. There was no variation among goat breeds in the
      sarcoma homology 3 (SH3) binding motif, the protein kinase C phosphorylation site
      or the two N-linked glycosylation sites. Exon 15 exhibited variability due to the
      presence of two polymorphic microsatellites. Genotyping of the upstream guanine
      thymine repeat (GTn) at 3'-UTR revealed eight alleles (GT11, GT12, GT14-GT19) in
      goats, whereas GT13 (present in cattle) was absent. Most goats carried the GT16
      allele and no allele was found to be exclusive to only one breed. The coefficient
      of genetic differentiation value (G(ST)) was 0.084. This microsatellite appears
      to be an informative DNA marker for genetic linkage analysis in goats.

PMID- 21071246
TI  - Characterization of a 3D MEMS fabricated micro-solenoid at 9.4 T.
AB  - We present for the first time a complete characterization of a micro-solenoid for
      high resolution MR imaging of mass- and volume-limited samples based on three
      dimensional B(0), B(1) per unit current (B(1)(unit)) and SNR maps. The micro
      solenoids are fabricated using a fully micro-electromechanical systems (MEMS)
      compatible process in conjunction with an automatic wire-bonder. We present 15
      MUm isotropic resolution 3D B(0) maps performed using the phase difference
      method. The resulting B(0) variation in the range of [-0.07 ppm to -0.157 ppm]
      around the coil center, compares favorably with the 0.5 ppm limit accepted for MR
      microscopy. 3D B(1)(unit) maps of 40 MUm isotropic voxel size were acquired
      according to the extended multi flip angle (ExMFA) method. The results
      demonstrate that the characterized microcoil provides a high and uniform
      sensitivity distribution around its center (B(1)(unit) = 3.4 mT/A +/- 3.86%)
      which is in agreement with the corresponding 1D theoretical data computed along
      the coil axis. The 3D SNR maps reveal a rather uniform signal distribution around
      the coil center with a mean value of 53.69 +/- 19%, in good agreement with the
      analytical 1D data along coil axis in the axial slice. Finally, we prove the
      microcoil capabilities for MR microscopy by imaging Eremosphaera viridis cells
      with 18 MUm isotropic resolution.

PMID- 21071247
TI  - Application of partial least squares and radial basis function neural networks in
      multivariate imaging analysis-quantitative structure activity relationship: study
      of cyclin dependent kinase 4 inhibitors.
AB  - The detailed application of multivariate image analysis (MIA) method for the
      evaluation of quantitative structure activity relationship (QSAR) of some cyclin
      dependent kinase 4 inhibitors is demonstrated. MIA is a type of data mining
      methods that is based on data sets obtained from 2D images. The purpose of this
      study is to construct a relationship between pixels of images of investigated
      compounds as independent and their bioactivities as a dependent variable. Partial
      least square (PLS) and principal components-radial basis function neural networks
      (PC-RBFNNs) were developed to obtain a statistical explanation of the activity of
      the molecules. The performance of developed models were tested by several
      validation methods such as external and internal tests and also criteria
      recommended by Tropsha and Roy. The resulted PLS model had a high statistical
      quality (R2 = 0.991 and R2(CV) = 0.993) for predicting the activity of the
      compounds. Because of high correlation between values of predicted and
      experimental activities, MIA-QSAR proved to be a highly predictive approach.

PMID- 21071248
TI  - Large fat and skin necroses after deep subcutaneous injections of a slow-release
      somatostatin analogue in a woman with acromegaly.
AB  - OBJECTIVE: Somatostatin analogues are the most commonly used drugs for treatment
      of acromegaly. Known side effects include gastrointestinal reactions,
      cholelithiasis, effects on glucose metabolism, and mild reactions at injection
      sites. We report a patient who developed fat and skin necroses after injections
      of a depot somatostatin analogue. SUBJECT: A woman with active acromegaly was
      given deep subcutaneous injections of an extended release formulation of
      lanreotide at alternate sides of the buttocks on three occasions over a ten week
      period. The regimen was then discontinued due to gastrointestinal complaints. One
      month later indurated subcutaneous nodules appeared at both sites. After another
      two months, the patient presented 10*10 cm lesions on the buttocks, with central
      erythematous zones and, at the site of two injections, a necrotic 5*3 cm ulcer.
      There were no signs of infection or systemic diseases. MRI revealed bilateral fat
      necroses. A month later, an ulcer developed at the second site. The ulcers were
      managed conservatively until clear demarcations were obtained, where after
      surgical revisions were performed. Eight months after the last injection, the
      wounds could be closed. CONCLUSION: The fat and skin necroses represent a side
      effect not previously described after deep subcutaneous injections. Possibly, the
      patient had an exceptional susceptibility to develop an inflammatory, foreign
      body like reaction that hypothetically was aggravated by a sustained anti
      angiogenic effect of the compound.

PMID- 21071249
TI  - Interaction between MMACHC and MMADHC, two human proteins participating in
      intracellular vitamin B12 metabolism.
AB  - The identification of eight genes involved in inherited cobalamin (Cbl) disorders
      has provided insight into the complexity of the vitamin B12 trafficking pathway.
      Detailed knowledge about the structure, interaction, and physiological functions
      for many of the gene products, including the MMACHC and MMADHC proteins, is
      lacking. Having cloned, expressed, and purified MMACHC in Escherichia coli, we
      demonstrated its monodispersity by dynamic light scattering and measured its
      hydrodynamic radius, either alone or in complex with each of four vitamin B12
      derivatives. Using solution-phase intrinsic fluorescence and label-free, real
      time surface plasmon resonance (SPR), MMACHC bound cyanocobalamin and
      hydroxycobalamin with similar low micromolar affinities (K(D) 6.4 and 9.8 MUM,
      respectively); adenosylcobalamin and methylcobalamin also shared similar binding
      affinities for MMACHC (K(D) 1.7 and 1.4 MUM, respectively). To predict specific
      regions of interaction between MMACHC and the proposed partner protein MMADHC,
      MMACHC was subjected to phage display. Five putative MMACHC-binding sites were
      identified. Finally, MMADHC was confirmed as a binding partner for MMACHC both in
      vitro (SPR) and in vivo (bacterial two-hybrid system).

PMID- 21071250
TI  - Novel mutations in the human MCCA and MCCB gene causing methylcrotonylglycinuria.
AB  - Methylcrotonylglycinuria (MCG) is an inborn error of leucine catabolism and has a
      recessive pattern of inheritance that results from the deficiency of 3
      methylcrotonyl-CoA carboxylase (MCC). The clinical phenotypes are highly variable
      ranging from neonatal onset with severe neurological involvement to asymptomatic
      adults. Here we identified two novel MCCA (exon 3: c.137G>A; p.46G>E), (IVS7-1G>A
      splice site mutation), and four novel MCCB (exon 11: c.1065A>T; p.355L>F), (exon
      15: c.1430A>G; p.477Q>R), (exon 16: c.1549G>A; p.517G>R), (exon 16: c.1559A>C;
      p.520Y>S) mutant alleles from five MCC-deficient patients.

PMID- 21071251
TI  - Prevalence of Bartonella species DNA and antibodies in cats (Felis catus)
      submitted to a spay/neuter program in Rio de Janeiro, Brazil.
AB  - The prevalence of Bartonella species DNA and antibodies for Bartonella henselae
      were studied in 40 clinically healthy cats (Felis catus, Linnaeus 1758) submitted
      to a spay/neuter program in Rio de Janeiro, Brazil. Additionally, the prevalence
      of Bartonella species DNA was investigated in the fleas found parasitizing the
      subject cats. For this purpose, blood samples were obtained from all cats, and
      DNA extraction was performed on the blood, and blood clotted samples, as well as
      on pools of fleas obtained from them. Antibodies for B henselae were detected on
      serum samples. Bartonella species DNA was detected in 17 cats, whereas serum
      reactivity for B henselae was found in 19. A total of 20 cats were flea-infested
      and nine of these 20 had Bartonella species DNA in their blood. In four of the 20
      flea-infested cats, Bartonella species DNA was detected in the fleas obtained
      from those cats, but only one of these four cats had Bartonella species DNA in
      its blood.

PMID- 21071252
TI  - Production of radioactive phantoms using a standard inkjet printer and the public
      domain multi-printing code GENIA.
AB  - The public domain code GENIA, based on multi-printing method for producing
      surface sources with appropriate radioactivity, is described. The conventional
      technique, running on standard inkjet printer with radio-marked ink filling, is
      improved by repeating elementary printing commands in the same band. Well
      outlined sources with adjustable radioactivity can be obtained without refilling.
      The intrinsic limitation of printable radioactivity, depending on the value
      available at nozzles at printing time, was overcome. In addition the method
      permits the accurate calibration of the amount of activity released onto the
      paper.

PMID- 21071253
TI  - Biocomputing: numerical simulation of glioblastoma growth and comparison with
      conventional irradiation margins.
AB  - OBJECT: Estimation of glioblastoma (GBM) growth patterns is of tremendous value
      in determining tumour margins for radiotherapy. We have previously developed a
      numerical simulation model for the pattern of spread of glioblastoma tumours.
      This model involved the creation of a digital atlas of the brain with elasticity
      and resistance-to-invasion values for specific brain structures and also included
      probable direction of tumour spread as estimated by Diffusion Tensor Imaging
      (DTI). The current study is aimed at comparing the outcome of such simulation
      with conventional irradiation margins currently in use. METHODS: Actual patient
      data were used to simulate the direction of microscopic extension, using a
      variety of margin-, proliferation- and diffusion-rate scenarios to generate
      growth patterns, which were then compared with current standard radiotherapy
      margins. RESULTS: Our patient growth pattern simulations showed microscopic
      invasion beyond irradiation margins for both combinations of high-diffusion/low
      proliferation and low-diffusion/high-proliferation rate scenarios. The model also
      indicated that some healthy brain tissue that was projected to be safe from
      recurrence fell inside treatment margins. CONCLUSION: These results may explain
      the current inadequacy of our treatment techniques in preventing locoregional
      recurrences of GBM.

PMID- 21071254
TI  - Factors impacting compliance with standard precautions in nursing, China.
AB  - OBJECTIVES: To evaluate registered nurse compliance with standard precautions and
      to analyze the factors that affect compliance. METHODS: Study data were collected
      over a 3-month period from June to September 2007. The survey research method was
      used. A total of 1500 randomly sampled registered nurses from 18 hospitals in
      Hunan, China completed self-report questionnaires. RESULTS: Of the 1500 nurses
      included in the study, 1444 returned valid self-report questionnaires. Compliance
      with standard precautions was found to be low in the surveyed nurses. With a
      maximum possible score of 80, the quartile range of the overall score for
      compliance for all nurses was 48.29 (upper quartile score 76.36, lower quartile
      score 28.07), which was occupied by 64.7% of the participants. The factors most
      affecting compliance were: standard precautions training (odds ratio (OR) 2.17,
      95% confidence interval (CI) 1.85-2.55) and knowledge (OR 1.94, 95% CI 1.01
      3.41), followed by hospital grade (OR 1.61, 95% CI 1.79-1.86), presence of sharps
      disposal box in the department (OR 1.43, 95% CI 1.10-3.41), general self-efficacy
      (OR 1.29, 95% CI 1.04-1.59), exposure experience (OR 0.69, 95% CI 0.56-0.85), and
      department in which the nurse worked (OR 1.24, 95% CI 1.05-1.46). CONCLUSIONS:
      The relevant authorities and hospital infection control department should pay
      more attention to nurse compliance with standard precautions. Standard
      precautions training should be strengthened and sufficient practical personal
      protection equipment provided in order to reduce hospital infections and protect
      the health of patients and medical staff.

PMID- 21071255
TI  - Left knee prosthesis-related Mycobacterium goodii infection.
AB  - Non-tuberculous mycobacteria are increasingly being recognized as important human
      pathogens. We present the case of a 44-year-old non-diabetic male who underwent
      left total knee arthroplasty for degenerative arthritis after trauma. He
      developed left knee swelling and progressively worsening pain over the next 4
      weeks. He was referred for treatment using whirlpool baths and developed a
      blister at the surgical incision site. Repeated aspirations of the left knee
      failed to show any growth of organism on routine cultures. He finally underwent
      explantation of the left knee prosthesis with antimicrobial spacer placement 4
      months later. Cultures of three different intra-operative specimens turned
      positive for Mycobacterium goodii. This infection was successfully treated with
      combination oral antimicrobials for 6 months. The patient underwent revision left
      knee arthroplasty subsequently and was symptom-free until his last follow-up
      visit 1 year later. This patient highlights the importance of testing for
      mycobacteria in prosthesis-related infections with previously negative routine
      bacterial cultures.

PMID- 21071256
TI  - Emergency management of traumatic collateral palmar digital nerve defect inferior
      to 30 mm by venous grafting. Report of 12 clinical cases.
AB  - INTRODUCTION: When traumatic collateral palmar digital nerve defect occurs,
      emergency venous grafting is an alternative to the two-step nervous grafting
      procedure. METHODS: During the course of a monocentric retrospective study, 12
      cases of emergency venous grafting were reviewed by a single independent examiner
      11 months, at least, post-intervention. Clinical and functional evaluation was
      carried out, together with a self-assessment of the results by the patient. Data
      were compacted using a filtering method and the final result was considered in
      terms of "good" or "bad". RESULTS: Good result was observed in ten cases out of
      12. Bad results were associated with poor sensory recovery in the two other
      cases. In one of these, the bad result was also related to severe symptoms in
      cold conditions and a troublesome hyperesthesia. DISCUSSION: Through a review of
      the literature, we justify the emergency treatment of nerve defects of the
      collateral palmar digital nerves with venous grafting.

PMID- 21071257
TI  - Synchronous pattern distinguishes resting tremor associated with essential tremor
      from rest tremor of Parkinson's disease.
AB  - Rest tremor associated with essential tremor (ET) is a condition that poses
      challenges in diagnosing Parkinson's disease (PD). We investigated tremor
      parameters in PD and ET patients with rest tremor. Fifteen patients with PD and
      15 patients with ET underwent electrophysiological examination to evaluate
      characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD
      patients was significantly higher than that of patients with ET (p = 0.002),
      whereas burst duration and frequency were significantly higher in ET than in PD
      group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed
      some overlap of these electrophysiological values with values from patients with
      ET. By contrast, rest tremor pattern showed no overlap between the two diseases,
      because all patients with ET presented a synchronous pattern whereas PD patients
      had an alternating pattern (p < 0.001), a finding that differentiated the
      patients on an individual basis. The electromyographic pattern of rest tremor may
      help to differentiate PD from ET.

PMID- 21071258
TI  - Comparative evaluation of multi-purpose solutions in the stabilization of tear
      lysozyme.
AB  - The range and extent of tear proteins removed by various multi-purpose solutions
      has been investigated, but there is little information in the literature about
      their ability to prevent denaturation of tear proteins, particularly lysozyme.
      The purpose of this study was to determine the ability of Bausch+Lomb BiotrueTM
      multi-purpose solution and other care solutions to affect denaturation of
      lysozyme using a lysozyme activity assay. The test solutions used were: Biotrue
      multi-purpose solution, Bausch+Lomb renu((r)) freshTM, formerly ReNu
      MultiPlus((r)), Alcon OPTI-FREE RepleniSH, Alcon OPTI-FREE EXPRESS, CIBA VISION
      AQuify, and AMO COMPLETE Multi-Purpose Solution Easy Rub Formula. A phosphate
      buffered saline (PBS) solution served as a control. The test and control
      solutions containing lysozyme were exposed to sodium dodecyl sulfate (SDS), a
      known denaturant of the enzyme. The assay was based on digestion of the cell wall
      of Micrococcus luteus in a suspension, a substrate sensitive to active lysozyme.
      Enzymatic activity against M. luteus was used to assess activity of lysozyme. The
      decrease in the turbidity of the cell wall suspension, a measure of relative
      enzyme activity, was determined by following the decrease in absorbance (at
      450nm) over time using a spectrophotometer. Statistically significant greater
      stabilization of lysozyme was observed with Biotrue multi-purpose solution and
      renu fresh than with OPTI-FREE RepleniSH, OPTI-FREE EXPRESS, AQuify, COMPLETE
      Multi-Purpose Solution Easy Rub Formula, and a PBS control. The lysozyme activity
      assay revealed that Biotrue multi-purpose solution and renu fresh have the
      ability to stabilize lysozyme under conditions that typically denature the
      protein.

PMID- 21071259
TI  - Residue-specific incorporation of non-canonical amino acids into proteins: recent
      developments and applications.
AB  - Residue-specific incorporation of non-canonical amino acids into proteins allows
      facile alteration and enhancement of protein properties. In this review, we
      describe recent technical developments and applications of residue-specific
      incorporation to problems ranging from elucidation of biochemical mechanisms to
      engineering of protein-based biomaterials. We hope to inform the reader of the
      ease and broad utility of residue-specific non-canonical amino acid incorporation
      with the goal of inspiring investigators outside the field to consider applying
      this tool to their own research.

PMID- 21071260
TI  - Protein-polymer conjugates: synthetic approaches by controlled radical
      polymerizations and interesting applications.
AB  - Protein-polymer conjugates are of interest to researchers in diverse fields.
      Attachment of polymers to proteins results in improved pharmacokinetics, which is
      important in medicine. From an engineering standpoint, conjugates are exciting
      because they exhibit properties of both the biomolecules and synthetic polymers.
      This allows the activity of the protein to be altered or tuned, anchoring to
      surfaces, and supramolecular self-assembly. Thus, there is broad interest in
      straightforward synthetic methods to prepare protein-polymer conjugates.
      Controlled radical polymerization (CRP) techniques have emerged as excellent
      strategies to make conjugates because the resulting polymers have narrow
      molecular weight distributions, targeted molecular weights, and attach to
      specific sites on proteins. Herein, recent advances in the synthesis and
      application of protein-polymer conjugates by CRP are highlighted.

PMID- 21071261
TI  - NMR-spectroscopic analysis of mixtures: from structure to function.
AB  - NMR spectroscopy as a particularly information-rich method offers unique
      opportunities for improving the structural and functional characterization of
      metabolomes, which will be essential for advancing the understanding of many
      biological processes. Whereas traditionally NMR spectroscopy was mostly relegated
      to the characterization of pure compounds, the past few years have seen a surge
      of interest in using NMR-spectroscopic techniques for characterizing complex
      metabolite mixtures. Development of new methods was motivated partly by the
      realization that using NMR for the analysis of metabolite mixtures can help
      identify otherwise inaccessible small molecules, for example compounds that are
      prone to chemical decomposition and thus cannot be isolated. Furthermore,
      comparative metabolomics and statistical analyses of NMR spectra have proven
      highly effective at identifying novel and known metabolites that correlate with
      changes in genotype or phenotype. In this review, we provide an overview of the
      range of NMR-spectroscopic techniques recently developed for characterizing
      metabolite mixtures, including methods used in discovery-oriented natural product
      chemistry, in the study of metabolite biosynthesis and function, or for
      comparative analyses of entire metabolomes.

PMID- 21071262
TI  - Wilm's tumor gene WT1 peptide immunotherapy for pulmonary metastasis from adenoid
      cystic carcinoma of the salivary gland.

PMID- 21071263
TI  - Establishment and characterization of a rabbit oral squamous cell carcinoma cell
      line as a model for in vivo studies.
AB  - The incidence of oral squamous cell carcinoma (SCC) is increasing but the long
      term survival rate remains low. An animal model would therefore be helpful for
      evaluation of new treatment modalities for oral SCC. Hamster is small animal,
      therefore, the cancer of hamster cheek pouch is not optimal for tumor imaging.
      The VX2 cell line has been used in many carcinoma-related studies, including oral
      SCC research, but it is derived from cutaneous tissue and not mucosa. We
      chemically induced tongue squamous cell carcinoma in rabbits and subsequently
      established a rabbit squamous cell line. The cells grew in multiple layers
      without contact inhibition for 60 passages over 2 years and were positive for
      cytokeratin (CK). Electron microscopy revealed that cells were polygonal with
      rich microvilli on the surface, and there were desmosomes between cells and
      bundles of tonofibril beside the cell membrane. The chromosome number ranged from
      71 to 272, with a modal value of 145 (12.4%). The cells were transplantable into
      nude mice subcutaneously or rabbit submucosally and produced carcinomas in all
      the animals. The cell line should be a useful tool for the study of the
      biological characteristics of oral SCC, especially tongue SCC.

PMID- 21071264
TI  - Modelling dynamic plant cells.
AB  - A major challenge in plant biology is to understand how functions in plant cells
      emerge from interactions between molecular components. Computational and
      mathematical modelling can encapsulate the relationships between molecular
      components and reveal how biological functions emerge. We review recent progress
      in modelling in metabolism, growth, signalling and circadian rhythms in plant
      cells. We discuss challenges and opportunities for future directions.

PMID- 21071265
TI  - Growth and development: eukaryotes.

PMID- 21071266
TI  - Analytical performance of norovirus real-time RT-PCR detection protocols in
      Canadian laboratories.
AB  - BACKGROUND: Noroviruses (NoVs) are the leading cause of infectious
      gastroenteritis worldwide. Real-time reverse transcription PCR (real-time RT-PCR)
      is the preferred method of NoV detection for the majority of testing
      laboratories. Although the accepted target region for molecular detection assays
      is the conserved ORF1/ORF2 junction, multiple variations have been published with
      differences in primers, probes, reagents, multiplexing, etc. OBJECTIVES: We
      assessed the detection limit for GII.4 NoV real-time RT-PCR assays as well as the
      ability to detect the non-GII.4 NoV genotypes in each participating laboratory.
      STUDY DESIGN: A panel of 25 RNA samples was circulated to 18 testing laboratories
      for comparison of their real-time RT-PCR procedures for NoV detection. RESULTS:
      Multiple protocols with slight differences in reagents or conditions successfully
      detected 10 genome equivalents or fewer of NoV per reaction. Multiplex procedures
      were significantly associated (p=0.04) with false negative results, particularly
      for a GI.2 strain. Sensitive detection was associated with false positive results
      (p=0.03). CONCLUSIONS: Overall, the data indicate that comparable results are
      produced under slightly different assay conditions.

PMID- 21071267
TI  - Neural responses in the occipital cortex to unrecognizable faces.
AB  - OBJECTIVE: Event-related potentials (ERPs) were recorded to examine neural
      responses to face stimuli in a masking paradigm. METHODS: Images of faces
      (neutral or fearful) and objects were presented in subthreshold, threshold, and
      suprathreshold conditions (exposure durations of approximately 20, 30 and 300 ms,
      respectively), followed by a 1000-ms pattern mask. We recorded ERP responses at
      Oz, T5, T6, Cz and Pz. The effects of physical stimulus features were examined by
      inverted stimuli. RESULTS: The occipital N1 amplitude (approximately 160 ms) was
      significantly smaller in response to faces than objects when presented at a
      subthreshold duration. In contrast, the occipitotemporal N170 amplitude was
      significantly greater in the threshold and suprathreshold conditions compared
      with the subthreshold condition for faces, but not for objects. The P1 amplitude
      (approximately 120 ms) elicited by upright faces in the subthreshold condition
      was significantly larger than for inverted faces. CONCLUSIONS: P1 and N1
      components at Oz were sensitive to subthreshold faces, which suggests the
      presence of fast face-specific process(es) prior to face-encoding. The N170
      reflects the robustness of the face selective response in the occipitotemporal
      area. SIGNIFICANCE: Even when presented for a subthreshold duration, faces were
      processed differently to images of objects at an early stage of visual
      processing.

PMID- 21071268
TI  - The routine circular coil is reliable in paired-TMS studies.
AB  - OBJECTIVE: Motor cortex excitability can be measured by transcranial magnetic
      stimulation (TMS) using different coil types, but paired-TMS was originally
      devised with a figure-of-eight coil. We asked whether the most popular, circular
      coil was suited to the every-day assessment of cortical excitability,
      particularly paired-TMS indexes, and if it reduced the measurement error.
      METHODS: We studied 12 right-handed, healthy subjects (34+/-7.6 years). Resting
      motor threshold (MT), cortical silent period (CSP), short-interval intracortical
      inhibition (SICI) at the 2, 3, 4 and 5 ms interstimulus intervals (ISIs) and
      intracortical facilitation (ICF) at the 14 and 16 ms ISIs were measured.
      Intrinsic variability of these indexes was evaluated in terms of Coefficients of
      Variation, to estimate the measurement error. This sequence was carried out both
      using a figure-of-eight coil over the hand motor area and a circular coil centred
      at the vertex. Testing was repeated 8-13 months later. RESULTS: On average, MT,
      SICI and ICF did not show any statistically significant difference (p>0.05) when
      studied with the figure-of-eight as compared with the circular coil. CSP was
      significantly shorter (p=0.007) with the figure-of-eight coil. Using either coil
      did not affect measurement variability. There was no significant session-to
      session group difference at any of the variables using either coil type.
      CONCLUSIONS: Except for the CSP duration, the TMS testing and retesting of
      cortical excitability, particularly the paired-pulse indexes, did not vary
      significantly as a function of the coil used. SIGNIFICANCE: Routine circular
      coils can be used reliably in paired-TMS studies designed to measure longitudinal
      changes in cortical excitability though they do not reduce the measurement error.

PMID- 21071269
TI  - New isolate of Trichoderma viride strain for enhanced cellulolytic enzyme complex
      production.
AB  - A new Trichoderma viride stain was isolated from Singapore soil samples. Its
      mutants were developed by using ethyl methyl sulfonate (EMS) treatment and UV
      irradiation followed by a semi-quantitative plate clearing assay on phosphoric
      acid-swollen cellulose plates. Mutant EU2-77 proved to be the most promising
      extracellular cellulase producer among 20 mutants in a screening program
      performed in shake flask fermentation after plate screening. Soluble protein
      content, filter paper cellulase (FPase) activity, beta-glucosidase activity and
      endoglucanase (CMCase) activity of the fermentation broths of the mutant strain
      were increased to 1.67, 2.49, 2.16, and 2.61 folds, respectively, compared with
      the wild strain. This enzyme complex produced by mutant EU2-77 contained FPase
      (2.19 IU/ml), CMCase (16.46 IU/ml), beta-glucosidase (4.04 IU/ml), xylanase
      (42.37 IU/ml), and beta-xylosidase (0.12 IU/ml). The soluble protein
      concentration in the enzyme complex was 1.69 mg/ml. The hydrolytic capacities of
      fermentation supernatants of T. reesei Rut-C30, the wild strain T. viride NP13a
      and mutant T. viride EU2-77 were compared with the commercial enzymes on the
      hydrolysis of waste newspaper. The crude enzymes prepared by T. viride EU2-77
      showed much higher hydrolysis performance than that from the commercial strain
      Rut-C30 and demonstrated much comparable hydrolytic performances with the
      commercial enzyme mixtures. T. viride mutant EU2-77 produced high levels of
      extracellular cellulases as well as beta-glucosidase, rendering the
      supplementation of beta-glucosidase unnecessary in waste newspaper hydrolysis.

PMID- 21071270
TI  - Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or
      metastatic biliary tract cancer: a phase 2 study.
AB  - BACKGROUND: Patients with biliary tract cancer have a poor prognosis, and, until
      recently, no standard palliative chemotherapy has been defined. We aimed to
      investigate the efficacy and safety of cetuximab in combination with gemcitabine
      and oxaliplatin (GEMOX) for first-line treatment of biliary tract cancer.
      METHODS: From Oct 1, 2006, to July 26, 2008, patients with unresectable locally
      advanced or metastatic biliary tract cancer were sequentially enrolled and
      treated at one centre in Austria. All patients received intravenous infusions of
      500 mg/m(2) cetuximab on day 1, 1000 mg/m(2) gemcitabine on day 1, and 100
      mg/m(2) oxaliplatin on day 2, every 2 weeks for 12 cycles. The primary outcome
      was overall response rate. Analysis was by intention to treat. Adverse reactions
      were assessed according to National Cancer Institute Common Toxicity Criteria.
      The study is completed and registered with ClinicalTrials.gov, number
      NCT01216345. FINDINGS: 30 patients with median age of 68 years (IQR 62-73) were
      enrolled and included in the analysis. Objective response occurred in 19 patients
      (63%; 95% CI 56.2-69.8), of whom three (10%; 3.2-16.8) achieved complete
      response, and 16 (53%; 46.2-59.8) achieved partial response. Nine patients
      underwent potentially curative secondary resection after major response to
      therapy. Grade 3 adverse events were recorded in 13 patients: skin rash (n=4),
      peripheral neuropathy (n=4), thrombocytopenia (n=3), nausea (n=1), diarrhoea
      (n=1), and neutropenia (n=1); no grade 4 adverse events were recorded.
      INTERPRETATION: Cetuximab plus GEMOX was well tolerated and had encouraging
      antitumour activity, leading to secondary resection in a third of patients. These
      findings warrant further study of cetuximab plus GEMOX in a large randomised
      trial.

PMID- 21071272
TI  - Novel targets in M. tuberculosis: search for new drugs.
AB  - The recent past has experienced a renaissance in tuberculosis (TB) research. New
      molecular biology reagents and genetic tools have been developed and whole genome
      sequences of Mycobacterium tuberculosis strains are now widely available. An
      increase in the prevalence of drug-resistant strains of M. tuberculosis has
      renewed focus on the development of new drugs against this millennia old disease.
      The identification of new targets in M. tuberculosis that might be inhibited to
      effectively kill the existing strains is now a global pursuit. This review
      summarizes recently identified targets in M. tuberculosis that have been
      validated beyond initial genetic identification. Advancing these defined targets
      for the development of inhibitors has the potential to produce new drugs with
      novel mechanisms of actions and benefit TB patients worldwide. 

PMID- 21071271
TI  - The contribution of Langerhans cells to cutaneous malignancy.
AB  - The skin is at the forefront of environmental exposures, such as ultraviolet
      radiation and a myriad of chemicals, and is at risk for malignant transformation.
      The skin is a highly responsive immunological organ that contains a unique
      population of immature intraepidermal dendritic cells (DCs) called Langerhans
      cells (LCs). Although LCs show morphological and migratory changes in response to
      epidermal perturbation, and can function as antigen-presenting cells to activate
      T cells, their role in carcinogenesis is unknown. Here we review recent studies
      that have provided clues to the potential roles that LCs might play in the
      pathogenesis of skin cancer, beyond their stimulation or regulation of adaptive
      immunity. Understanding this role of LCs might provide new perspectives on the
      relevance of DC populations that are resident within other epithelial tissues for
      cancer.

PMID- 21071273
TI  - Narrative pedagogy and simulation: future directions for nursing education.
AB  - Narrative pedagogy has been developed over the last decade in nursing as a means
      of complementing a conventional content and competency driven pedagogy. It
      focuses attention on the human experience of health care by deriving shared
      meanings from interpretation of stories. This allows students to explore the
      different perspectives of those involved. The emotional experiences of
      participants can be understood, conventional wisdom challenged and new knowledge
      emerge as students work together to construct their learning. Individual stories
      are embedded within the narrative and teachers have successfully used literature
      and film as narratives to help them explore the meaning of health care with
      students. Modern technology has opened up a new range of electronic narratives
      such as virtual simulation. These are considered and rejected as devices for a
      health care narrative due to their dehumanized and unrealistic nature. However it
      is argued that a multimedia online simulation of a typical neighbourhood can
      achieve the goal of providing a suitable narrative. Human actors replace avatars
      and real world settings replace gaming environments as the stories of people in
      this community are related and used to support narrative pedagogy. An example of
      such a narrative developed jointly in the UK and Canada is discussed.

PMID- 21071274
TI  - Initial evaluation of Stilwell: a multimedia virtual community.
AB  - Narrative pedagogy has emerged in the last decade as a new approach designed to
      complement the conventional approaches to education. It is concerned with
      understanding the meaning of events to people, appreciating multiple perspectives
      and the emotional content of health care. However there is a paucity of
      evaluative research concerning its impact. We have used narrative pedagogy to
      create Stilwell, a realistic narrative telling the stories of 60 characters
      living in a typical community. Stilwell is a real place (fictional name) and our
      multimedia model brings the community to life as a virtual practicum for a wide
      range of health professional students. This paper presents the results of our
      initial focus group evaluation of student learning experiences with Stilwell. The
      data indicates students found it a very different way of learning which allowed
      them to relate theory to practice in ways they had never done before. The realism
      of Stilwell was a challenge and generated considerable student emotional
      involvement with the characters, leading to significant novel learning activity.
      We reflect on how student feedback has allowed us to shape and improve Stilwell
      as it develops.

PMID- 21071275
TI  - Complementary therapies in healthcare: design, implementation and evaluation of
      an elective course for undergraduate students.
AB  - Complementary therapies are making a significant and cost effective contribution
      to the health of the community, especially in relation to chronic disease
      management and prevention of disease. Because of the increased use of
      complementary therapies, nurses, and other health professionals need to be
      familiar with specific practices so that they can assist clients to make informed
      decisions in the use of these therapies. Importantly, with the increased interest
      in complementary therapies, there is a need to ensure these practices are safe,
      cause no harm and are used to enhance the well-being of patients. This paper
      reports on the design, implementation and evaluation of a complementary therapies
      course and a linked Thai cultural studies tour. The course was implemented at The
      University of Newcastle for the first time in 2009 with an enrollment of 200
      students. It is an elective course for both nursing students and those from other
      disciplines. In this paper we describe the reasons for the introduction of this
      course and its value in nursing education. We then provide an overview of the
      course and report on evaluation results from both the course and the Thai
      cultural studies tour.

PMID- 21071276
TI  - Legacy Mentors: translating the wisdom of our senior nurses.
AB  - 'Legacy Mentors' are nurses aged 55 or older with a wealth of knowledge and
      passion to share with other nurses. Finding ways to capture their wisdom,
      disseminate their expertise, and potentially retain them longer is critical. As
      part of an innovative Educator Pathway project in two health authorities in
      British Columbia, Canada, nurses with up to 40 years of experience proposed to
      share their wisdom and translate their expertise for the next generation of
      nurses. The Legacy Mentor Project involved 29 nurses who developed projects to
      share knowledge with students, novice and experienced nurses in their work
      settings. The project included an orientation workshop to facilitate project
      start-up, a mid-way workshop for sharing progress, and a celebration event in
      September 2009 which highlighted their learning and final outcomes in. Project
      evaluation through surveys, focus groups and interviews revealed that the nurses'
      expertise was validated, suggesting that the translation of expertise by re
      energized nurses is a strategy with potential to enhance retention of our most
      experienced nurses while also enhancing practice learning environments.
      Unexpected outcomes were reciprocal learning and changing practice of nursing
      peers through modelling and discussion. This paper will describe the process and
      outcomes of this pilot project, including description of the projects completed
      by the Legacy Mentors.

PMID- 21071277
TI  - The risk of transmitting prion disease by blood or plasma products.
AB  - Various experimental studies have shown infectivity in blood in relation to
      bovine spongiform encephalitis (BSE) and variant Creutzfeldt-Jakob disease
      (vCJD). Human to human transmission vCJD infection has been reported via
      transfusion of non-leukocyte-reduced red cells and, probably, via factor VIII
      concentrates. A number of precautionary measures are in place but uncertainties
      remain, especially concerning the number of BSE-infected people in the
      population. Additional measures such as prion filtration need consideration.

PMID- 21071278
TI  - Women's experiences and behaviour at onset of symptoms of ST segment elevation
      acute myocardial infarction.
AB  - BACKGROUND: Minimizing time from onset of symptoms to treatment (treatment delay)
      is crucial for patients with ST segment elevation acute myocardial infarction
      (STEMI), and one of the great challenges is to reduce the delay relating to the
      prehospital behaviour of the patient (patient delay). Studies indicate that women
      delay longer than men and insights into this area could lead to improved health
      education programmes aimed at reducing patient delay in women with STEMI. METHOD:
      Open interviews with 14 women with STEMI were held during their hospital stay
      from June to September 2009. The interviews were aimed at exploring determinants
      of treatment delay, and were carried out and analysed within a phenomenological
      framework. FINDINGS: Three themes emerged important for the delay in seeking
      medical assistance: (1) Knowledge and ideas of AMI symptoms and risks. (2)
      Ambivalence whether to call for medical assistance or to cope with the situation.
      (3) Actions and strategies taken after onset of symptoms. CONCLUSIONS: Three
      factors determined whether women showed appropriate behaviour for reduced patient
      delay after onset of symptoms: (1) identifying the symptoms as being of cardiac
      origin, (2) having a prepared action plan in case of an emergency situation, and
      (3) living with someone or contacting other persons.

PMID- 21071280
TI  - The pitfalls of BladderScanTM PVR in evaluating bladder volume in adolescent
      females.
AB  - Post-void residual (PVR) determination is an integral part of the evaluation of
      children presenting with lower urinary tract symptoms. Historically the PVR
      volume has been obtained by urinary catheterization after the child has voided,
      however, with the advent of ultrasound technology, PVR was determined in a
      noninvasive fashion by radiology personnel. Currently, PVR determinations may be
      obtained by healthcare personnel (without specialized training) using a portable,
      self calculating ultrasound; the BladderScan. While BladderScan PVR has been
      shown to be accurate and reproducible, it cannot differentiate between a
      distended bladder and other cystic pelvic structures. Several case reports have
      been published illustrating falsely elevated PVRs by bladder scan in adults with
      cystic pelvic structures. We present two adolescent females with LUTS who had
      falsely elevated PVRs by bladder scan, who, subsequently, underwent formal
      imaging to identify ovarian cystic pathology. To our knowledge, this is the first
      report of falsely elevated bladder scan PVR in children related to cystic pelvic
      organ pathology.

PMID- 21071279
TI  - Social status, health-related quality of life, and event-free survival in
      patients with heart failure.
AB  - BACKGROUND: Social status may impact health-related quality of life (HRQOL),
      hospitalization, and mortality in patients with heart failure (HF). PURPOSE: To
      determine if social status was associated with HRQOL and event-free survival.
      HYPOTHESES: Higher social status (quality of perceived support, emotional
      support, marital status, and economic status) is related to better HRQOL and
      event-free survival after controlling covariates (New York Heart Association
      [NYHA] functional class, comorbidity status, and age). METHODS: Patients (N =
      147, 61 +/- 11 years old, 70% male, 62% NYHA class III/IV) provided data on HRQOL
      (measured by the Minnesota Living with Heart Failure questionnaire) and social
      status. Event-free survival data were collected by medical record reviews and
      patient or family interviews. Hierarchical regression analysis and survival
      analysis were used to test the hypothesis. RESULTS: Better quality of perceived
      support, better economic status, better functional status, older age, and less
      comorbidity were related to better HRQOL (R2 = .365, p = <.001). Only economic
      status predicted event-free survival. CONCLUSION: Attention should be given to
      those who have lower social support to improve HRQOL and those who have lower
      economic status to improve event-free survival.

PMID- 21071281
TI  - The psychology of fear of flying (part II): a critical evaluation of current
      perspectives on approaches to treatment.
AB  - This is the second of a two part review which critically evaluates research
      published in disparate sources into the psychological treatment of fear of
      flying. Part I established fear of flying as a complex heterogeneous clinical
      phenomenon. This paper discusses the way in which evidence from clinical trials
      translates to best practice in treating fear of flying. Published research on
      psychological interventions uses terminology which bears a close resemblance to
      cognitive behavioural therapy. It is, however, questionable whether some
      treatment approaches reflect the implementation of the cognitive behavioural
      model as it is described in the wider literature on the treatment of anxiety
      disorders. This review evaluates a synthesis of published research which
      considers fear of flying and related anxiety disorders with the aim of deriving
      best practice. It concludes that the most effective psychological interventions
      will be those based on an accurate functional assessment of an individual and
      their social context relevant to fear of flying and not merely a set of standard
      and invariant protocols. Most published research has been carried out on
      participants who self refer or volunteer for treatment and it is probable that
      this is a biased clinical group which may distort reported efficacy and treatment
      outcomes. It concludes by highlighting directions for future research and the
      development of psychological treatments for fear of flying.

PMID- 21071282
TI  - Clinical findings and management of conjunctival intraepithelial neoplasia.
AB  - BACKGROUND: Conjunctival intraepithelial neoplasia (CIN) is the most common tumor
      of the ocular surface and is a precursor to invasive squamous cell carcinoma. CIN
      comprises a spectrum of premalignant epithelial neoplasia that usually begins
      near the limbus and spreads to the cornea. METHODS: This case report reviews the
      clinical findings and management of CIN, with a discussion of the histopathology
      and etiology of this tumor. CONCLUSION: CIN has a variety of clinical
      presentations, including gelatinous, leukoplakic, or papilliform. Because of
      their malignant potential, these lesions must be differentiated carefully and
      treated promptly. Traditional management of CIN is surgical excision with
      cryotherapy, but other topical treatments are being explored with promising
      results.

PMID- 21071283
TI  - Skin vascular resistance in the standing position increases significantly after 7
      days of dry immersion.
AB  - Actual and simulated microgravity induces hypovolemia and cardiovascular
      deconditioning, associated with vascular dysfunction. We hypothesized that
      vasoconstriction of skin microcirculatory bed should be altered following 7 days
      of simulated microgravity in order to maintain cardiovascular homeostasis during
      active standing. Eight healthy men were studied before and after 7 days of
      simulated microgravity modeled by dry immersion (DI). Changes of plasma volume
      and orthostatic tolerance were evaluated. Calf skin blood flow (laser-Doppler
      flowmetry), ECG and blood pressure signal during a 10-min stand test were
      recorded, and skin vascular resistance, central hemodynamics, baroreflex
      sensitivity and heart rate variability were estimated. After DI we observed
      increased calf skin vascular resistance in the standing position (12.0 +/- 1.0 AU
      after- vs. 6.8 +/- 1.4 AU-before), while supine it was unchanged. Cardiovascular
      deconditioning was confirmed by greater tachycardia on standing and by
      hypovolemia (-16 +/- 3% at day 7 of DI). Total peripheral resistance and indices
      of cardiovascular autonomic control were not modified. In conclusion, unchanged
      autonomic control and total peripheral resistance suggest that increased skin
      vasoconstriction to standing involves rather local mechanisms-as venoarteriolar
      reflex-and might compensate insufficient vasoconstriction of other vascular beds.

PMID- 21071284
TI  - Autonomic control of the eye and the iris.
AB  - The vertebrate eye receives innervation from ciliary and pterygopalatine
      parasympathetic and cervical sympathetic ganglia as well as sensory trigeminal
      axons. The sympathetic and parasympathetic pathways represent the classical
      "core" of neural regulation of ocular homeostasis. Sensory trigeminal neurons are
      also involved in autonomic regulation by both providing the afferent limb of
      various reflexes and exerting their peptide-mediated local effector function.
      This arrangement is remarkably conserved throughout vertebrate classes although
      significant modifications are observed in anamniotes, in particular their irises.
      In higher primates and birds, intrinsic choroidal neurons emerged as a
      significant additional innervation component. They most likely mediate local
      vascular regulation and other local homeostatic tasks in foveate eyes. This
      review across the vertebrate classes outfolds the complex neuronal regulatory
      underpinnings across vertebrates that ensure proper visual function.

PMID- 21071286
TI  - Neurosteroid modulation of arterial baroreflex function in the rostral
      ventrolateral medulla.
AB  - Through both genomic and nongenomic actions, ovarian hormones and their
      metabolites have significant effects on the central nervous system to modulate a
      variety of regulatory systems, including the cardiovascular system. The major
      metabolite of progesterone, 3alpha-hydroxy-dihydroprogesterone, is the most
      potent endogenous positive modulator of GABA(A) receptors known and central
      nervous system levels of this progesterone metabolite fluctuate with the ovarian
      cycle and are elevated in pregnant animals. Pregnancy is associated with
      attenuated arterial baroreflex sympathoexcitation and increased tonic GABAergic
      inhibition of the rostral ventrolateral medulla (RVLM) likely contributes. The
      current experiments were performed to determine if the effects of pregnancy on
      arterial baroreflex control of renal sympathetic nerve activity could be mimicked
      by microinjection of the neuroactive progesterone metabolite into the RVLM.
      Compared to control values, 15 min after microinjection of 3alpha-hydroxy
      dihydroprogesterone into the RVLM (n=10), baseline renal sympathetic nerve
      activity was decreased to 82% of baseline, and the range (157+/-10 to 131+/-11%)
      and maximum nerve activity (164+/-9 to 136+/-12%) for the arterial baroreflex
      curves were decreased. In contrast, microinjection of the inactive isomer, 3beta
      hydroxy-dihydroprogesterone into the RVLM (n=9), had no effect on baseline nerve
      activity or the arterial baroreflex nerve activity range or maximum. Thus,
      although multiple mechanisms likely contribute to pregnancy associated changes in
      baroreflex function, these experiments suggest that increased levels of 3alpha
      hydroxy-dihydroprogesterone in the RVLM might contribute.

PMID- 21071287
TI  - Anti-inflammatory effect of vagus nerve stimulation in a rat model of
      inflammatory bowel disease.
AB  - Vagus nerve stimulation of afferents is used as an adjunctive treatment for drug
      resistant epilepsy and depression. In addition, anti-inflammatory properties of
      vagus nerve stimulation have been reported in various experimental models of
      inflammation but not in colitis. These effects are thought to be mediated via
      peripheral release of acetylcholine from the vagus and subsequent activation of
      macrophages. Our aim was to evaluate in rats the anti-inflammatory effects of
      chronic vagus nerve stimulation on colonic inflammation. Colitis was induced by
      intracolonic instillation of trinitrobenzene sulfonic acid. Vagus nerve
      stimulation (left cervical) was performed in freely moving animals 3 h per day
      for five consecutive days. Assessment of colonic inflammation was obtained using
      physiological (e.g. body weight, temperature and locomotor activity) parameters,
      macroscopical (area of lesions), histological, and biological parameters (e.g.
      myeloperoxidase activity, cytokine and cytokine-related mRNAs), both at the level
      of the damaged colon and the colon immediately above. A global multivariate index
      of colitis was then generated for a better characterization of colonic
      inflammation. Vagus nerve stimulation reduced the degree of body weight loss and
      inflammatory markers as observed above the lesion by histological score and
      myeloperoxidase quantification. This anti-inflammatory effect was also
      demonstrated by the improvement of the multivariate index of colitis. These data
      argue for an anti-inflammatory role of vagus nerve stimulation chronically
      performed in freely moving rats with colitis and provide potential therapeutic
      applications for patients with inflammatory bowel diseases.

PMID- 21071288
TI  - Dexamethasone quantification in dried blood spot samples using LC-MS: The
      potential for application to neonatal pharmacokinetic studies.
AB  - A high-performance liquid chromatography (LC-MS) method has been developed and
      validated for the determination of dexamethasone in dried blood spot (DBS)
      samples. For the preparation of DBS samples whole blood spiked with analyte was
      used to produce 30MUl blood spots on specimen collection cards. An 8mm disc was
      cut from the DBS sample and extracted using a combination of methanol: water
      (70:30, v/v) containing the internal standard, triamcinolone acetonide. Extracts
      were centrifuged and chromatographic separation was achieved using a Zorbax
      Eclipse Plus C18 column using gradient elution with a mobile phase of
      acetonitrile and water with formic acid at a flow rate of 0.2ml/min. LC-MS
      detection was conducted with single ion monitoring using target ions at m/z 393.1
      for dexamethasone and 435.1 for the internal standard. The developed method was
      linear within the tested calibration range of 15-800ng/ml. The overall extraction
      recovery of dexamethasone from DBS samples was 99.3% (94.3-105.7%). The accuracy
      (relative error) and precision (coefficient of variation) values were within the
      pre-defined limits of <=15% at all concentrations. Factors with potential to
      affect drug quantification measurements such as blood haematocrit, the volume of
      blood applied onto the collection card and spotting device were investigated.
      Although a haematocrit related effect was apparent, the assay accuracy and
      precision values remained within the 15% variability limit with fluctuations in
      haematocrit of +/-5%. Variations in the volume of blood spotted did not appear to
      affect the performance of the developed assay. Similar observations were made
      regarding the spotting device used. The methodology has been applied to determine
      levels of dexamethasone in DBS samples collected from premature neonates. The
      measured concentrations were successfully evaluated using a simple 1-compartment
      pharmacokinetic model. Requiring only a microvolume (30MUl) blood sample for
      analysis, the developed assay is particularly suited to pharmacokinetic studies
      involving paediatric populations.

PMID- 21071289
TI  - Review on the analysis of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and its
      phase I and phase II metabolites in biological matrices, foodstuff and beverages.
AB  - The heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP), has been shown to be carcinogenic in rodents, mice and rats. Following
      phase I N-hydroxylation and phase II esterification PhIP exerts its carcinogenic
      effect by binding to DNA purines. Quantitative and qualitative analysis of its
      bioactivated metabolites as well as it detoxification products is important in
      studying its biological effects and inter- and intra-individual exposures. A
      review is presented with an extensive coverage of publications specifically
      reporting on the analysis of PhIP and its phase I and II metabolites in
      biological matrices, foodstuff and beverages. Analytical techniques such as
      liquid and gas chromatography coupled with various detection techniques (mass
      spectrometry, ultraviolet or fluorescence detection) were mostly applied. We
      conclude that since the initial identification of PhIP in 1986 a large set of
      assays has been developed for the analysis of PhIP and its phase I and phase II
      metabolites in a wide range of matrices, these included food products and
      biological samples such as plasma, urine and faeces. In addition, it was shown
      that numerous metabolites were recovered and identified. Thus, we conclude that
      liquid chromatography coupled to mass spectrometry is clearly the method of
      choice for sensitive qualitative as well as quantitative analysis with high
      selectivity and reaching lower quantification levels in the sub pg/mL range. The
      main aim of this review is that it can be used by other researchers as a resource
      for method development and optimization of analytical methods of PhIP and its
      carcinogenic or detoxification products.

PMID- 21071290
TI  - Determination of solifenacin in human plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - A liquid chromatography-electrospray tandem mass spectrometry method was
      developed and validated to quantitate solifenacin in human plasma. The assay was
      based on protein precipitation with methanol and liquid chromatography performed
      on a pentafluorophenylpropylsilica column (50*4mm, 3MUm particles), the mobile
      phase consisted of methanol - 100mM ammonium acetate containing 1% of formic acid
      (90:10, v/v). Quantification was through positive-ion mode and selected reaction
      monitoring at m/z 363->193 and 368->198 for solifenacin and the internal standard
      solifenacin-D(5), respectively. The lower limit of quantitation was 0.47ng/ml
      using 0.25ml of plasma and linearity was demonstrated up to 42ng/ml. Intra-assay
      and inter-assay precision expressed by relative standard deviation was less than
      11% and inaccuracy did not exceed 11% at all levels. The assay was applied to the
      analysis of samples from a pharmacokinetic study.

PMID- 21071291
TI  - Design in nature, thermodynamics, and the constructal law: comment on "Life,
      hierarchy, and the thermodynamic machinery of planet Earth" by A. Kleidon.

PMID- 21071292
TI  - How would life factor in the evolution of planetary interiors? Comment on "Life,
      hierarchy, and the thermodynamic machinery of planet Earth" by A. Kleidon.

PMID- 21071294
TI  - Invited commentary.

PMID- 21071295
TI  - Use of latissimus dorsi perforator flap to facilitate simultaneous great toe-to
      thumb transfer in hand salvage.
AB  - Severe crushing and degloving injury of the hand often involves multiple tissue
      structures requiring several stages of reconstructions. This is more challenging
      when tissue defect and loss of thumb co-exist, requiring vascularised tissue
      transfer and toe-to-thumb reconstruction in a hand that has severely compromised
      vascularity. The management variables to be considered include the use of
      pedicled or free flap, simultaneous or staged procedures, consideration for early
      rehabilitation and flap selection to facilitate simultaneous free tissue
      transfers without further jeopardy to the vascularity of the hand. We illustrate
      these considerations in a case we have managed with simultaneous application of a
      latissimus dorsi perforator flap and great toe-to-thumb transfer.

PMID- 21071296
TI  - The cost-effectiveness of interventions in diabetes: a review of published
      economic evaluations in the UK setting, with an eye on the future.
AB  - AIM: To synthesise key outcomes data from cost-effectiveness studies in diabetes,
      in the UK setting, and describe a narrative for the evidence-base, in order to
      understand the direction that future health economics research in this field
      could be heading. METHODS: The peer-reviewed literature was searched at
      http://www.pubmed.com for health economics analyses in diabetes in the UK setting
      published between 1995 and 2008, using the keywords: "costs", "cost
      effectiveness", "diabetes", "UK". Studies on screening for diabetes or prevention
      of diabetes were excluded, along with studies that looked purely at cost of
      diabetes treatment or monitoring. RESULTS: There were over 350 hits on MEDLINE. A
      total of 23 articles were identified and reviewed. 18 studies were in type 2, two
      in type 1 and three studies in both types 1 and type 2 diabetes. All studies
      evaluated treatment from the perspective of the NHS, with the time horizons
      varying from 12 months to patient lifetimes. 13 studies estimated quality
      adjusted life expectancy (QALE). The majority of studies used health economics
      modelling techniques to project clinical benefit and cost outcomes beyond the
      context of clinical trials, with Markov-type models predominating. The United
      Kingdom Prospective Study of Diabetes was the most frequently cited source of
      clinical effectiveness and cost data. Most studies were funded by the
      pharmaceutical industry and evaluated more expensive products, rather than
      cheaper generic therapies such as human insulin and metformin monotherapy.
      CONCLUSION: Treatment-to-target in patients with diabetes in the UK is generally
      cost-effective and sometimes cost-saving vs. standard care. Ongoing health
      economics analysis in diabetes is essential as new clinical data are published.
      Future analysis of clinical and cost outcomes in diabetes could be expected to
      look beyond the impact of interventions on HbA1c in isolation, as manufacturers
      seek to differentiate innovative products in the market. Furthermore, it is
      anticipated that the competitiveness in the market for interventions in diabetes
      will lead to future cost-effectiveness analysis taking more interest in
      comparisons of off-patent medication and generic, fixed-dose combination
      therapies.

PMID- 21071297
TI  - Developmental validation of the PowerPlex((r)) ESI 16 and PowerPlex((r)) ESI 17
      Systems: STR multiplexes for the new European standard.
AB  - In response to the ENFSI and EDNAP groups' call for new STR multiplexes for
      Europe, Promega((r)) developed a suite of four new DNA profiling kits. This paper
      describes the developmental validation study performed on the PowerPlex((r)) ESI
      16 (European Standard Investigator 16) and the PowerPlex((r)) ESI 17 Systems. The
      PowerPlex((r)) ESI 16 System combines the 11 loci compatible with the UK National
      DNA Database((r)), contained within the AmpFlSTR((r)) SGM Plus((r)) PCR
      Amplification Kit, with five additional loci: D2S441, D10S1248, D22S1045, D1S1656
      and D12S391. The multiplex was designed to reduce the amplicon size of the loci
      found in the AmpFlSTR((r)) SGM Plus((r)) kit. This design facilitates increased
      robustness and amplification success for the loci used in the national DNA
      databases created in many countries, when analyzing degraded DNA samples. The
      PowerPlex((r)) ESI 17 System amplifies the same loci as the PowerPlex((r)) ESI 16
      System, but with the addition of a primer pair for the SE33 locus. Tests were
      designed to address the developmental validation guidelines issued by the
      Scientific Working Group on DNA Analysis Methods (SWGDAM), and those of the DNA
      Advisory Board (DAB). Samples processed include DNA mixtures, PCR reactions
      spiked with inhibitors, a sensitivity series, and 306 United Kingdom donor
      samples to determine concordance with data generated with the AmpFlSTR((r)) SGM
      Plus((r)) kit. Allele frequencies from 242 white Caucasian samples collected in
      the United Kingdom are also presented. The PowerPlex((r)) ESI 16 and ESI 17
      Systems are robust and sensitive tools, suitable for the analysis of forensic DNA
      samples. Full profiles were routinely observed with 62.5pg of a fully
      heterozygous single source DNA template. This high level of sensitivity was found
      to impact on mixture analyses, where 54-86% of unique minor contributor alleles
      were routinely observed in a 1:19 mixture ratio. Improved sensitivity combined
      with the robustness afforded by smaller amplicons has substantially improved the
      quantity of data obtained from degraded samples, and the improved chemistry
      confers exceptional tolerance to high levels of laboratory prepared inhibitors.

PMID- 21071298
TI  - Integrated sample cleanup and capillary array electrophoresis microchip for
      forensic short tandem repeat analysis.
AB  - A twelve-lane capillary array electrophoresis (CAE) microsystem is developed that
      utilizes an efficient inline capture injection process together with the
      classical radial microfabricated capillary array electrophoresis (MUCAE) format
      for high-sensitivity forensic short tandem repeat (STR) analysis. Biotin-labeled
      9-plex STR amplicons are captured in a photopolymerized gel plug via the strong
      binding of streptavidin and biotin, followed by efficient washing and thermal
      release for CE separation. The analysis of 12 STR samples is completed in 30 min
      without any manual process intervention. A comparison between capture inline
      injection and conventional cross injection demonstrated at least 10-fold
      improvement in sensitivity. The limit-of-detection of the capture-CAE system was
      determined to be 35 haploid copies (17-18 diploid copies) of input DNA; this
      detection limit approaches the theoretical limits calculated using Poisson
      statistics and the spectral sensitivity of the instrument. To evaluate the
      capability of this microsystem for low-copy-number (LCN) analysis, three touch
      evidence samples recovered from unfired bullet cartridges in a pistol submerged
      in water for an hour were successfully analyzed, providing 53, 71, and 59% of the
      DNA profile. The high-throughput capture-CAE microsystem presented here provides
      a more robust and more sensitive platform for conventional as well as LCN and
      degraded DNA analysis.

PMID- 21071299
TI  - Cholesteatoma of the frontal sinus.
AB  - PURPOSE OF STUDY: Cholesteatoma of the paranasal sinuses is a rare pathology. A
      review of the literature reported less than 30 cases. These lesions mainly
      involve the frontal sinus. CASE REPORT: A 25-year-old man presented with a right
      painful fronto-orbital mass associated with an ipsilateral eyelid oedema and a
      fever as high as 40 degrees C. He experienced a general epileptic seizure
      requiring his admission in an intensive care unit. CT-Scan with iodine injection
      evidenced the opacification of the right frontal sinus with bone lysis of the
      posterior wall. Complete surgical resection of a cystic structure containing
      keratin material was performed via eyebrow incision. The pathological examination
      confirmed the diagnosis of sinus cholesteatoma. Neurological signs entirely
      disappeared after surgery. Craniofacial MRI realized 2 months later showed no
      sign of recurrence. Obliteration of the right frontal sinus was performed 4
      months later. CONCLUSION: Although benign, cholesteatoma can spread to the
      surrounding structures leading to several complications including infections that
      can be life-threatening for the patient. CT-scan and MRI are useful examinations
      for diagnosis and follow-up. Complete surgical resection is required in order to
      avoid recurrence.

PMID- 21071301
TI  - [A baron Levay for the 21st century. The commemoration of the native village of
      Prof. Janos Feher].

PMID- 21071302
TI  - [Insula, a "mysterious" island in our brain -- minireview].
AB  - Until the last decade of the past century, insula was one of the less frequently
      investigated cortical areas in the human brain. Due to the introduction and wide
      use of neuroimaging techniques in human brain, insula became the focus of
      attention. Recent studies confirmed former observations about the presence of the
      olfactory, taste and viscerosensory cortical centers in the insula, and provided
      very fine new information about the mechanism of actions and interactions of
      these activities. Furthermore, the functional significance of insula in social
      emotional, cognitive and sensorimotor network, speech and language processes, as
      well as in interoceptive awareness have been determined. For performing of these
      activities, insula receives extensive neuronal input from the body and from
      various cortical areas. Through its opercular cortices and the anterior cingulate
      cortex, insula is connected to prefrontal, premotor, limbic and central autonomic
      areas. With our present knowledge, insula may serve as primary (unimodal)
      cortical area for olfactory, taste and viscerosensory information, and acts as a
      multimodal cortical association area in the emotional, cognitive, limbic and
      autonomic systems in the brain.

PMID- 21071303
TI  - [Neuroimmuno-modulation in gastric mucosa].
AB  - Several neuropeptides were supposed to take place in the protection of gastric
      mucosa and play role in the development of gastritis. AIM OF THE STUDY: To
      investigate morphological relationship between nerve fibres and immunocytes, to
      find out if these cells synthetize some neuropeptides and if there is there any
      co-existence with TNF-alpha and NFkappa-B. METHODS: Immunohistochemical, confocal
      laser microscopic methods were used to investigate nerve fibres, immunocompetent
      cells in control and gastritis mucosa. RESULTS: The number of neuropeptide
      containing nerve fibres increased significantly. In control stomach the number of
      lymphocytes, plasma cells, and mast cells was low and showed no immunoreactivity
      for neuropeptide antibodies. However, in gastritis, some of the immunocompetent
      cells were immunoreactive for SP and for NPY. Some of the SP immunoreactive cells
      showed also positive reaction for TNF-alpha and NFkappa-B. The distance between
      nerve fibres and immunocytes was 1 um or less. CONCLUSIONS: The increase of
      neuropeptides released from nerve fibres and immunocompetent cells can take part
      in neurogenic inflammation and generate chronic gastritis.

PMID- 21071304
TI  - [Research in the PhD Program led by Janos Feher between 1993 and 2010 at the
      Biochemical Research Laboratory, 2nd Department of Medicine, Semmelweis
      University].
AB  - Author wish to express gratitude to late professor Janos Feher for the invitation
      to participate in "Free Radical and Immunological References of Hepatology" PhD
      program in 1993 and for providing opportunity to establish a laboratory at the
      2nd Department of Medicine, Semmelweis University. He established a joint medical
      and biological research that is continuing unbrokenly. In this research group,
      between 1993 and 2010, eleven Ph.D. students received their scientific degrees
      and two candidate dissertations were prepared. Three students are working in this
      very exciting field even today. Author would like to salute before Janos Feher's
      remembrance by giving a list of results of topics under her leadership.

PMID- 21071306
TI  - [Fatty liver and global cardiometabolic risk].
AB  - Non-alcoholic fatty liver disease (NAFLD) can be found in approximately 30% of
      adults in industrialized societies. Non-alcoholic steatohepatitis (NASH) is its
      most severe histological form and progresses to cirrhosis in 20% of these
      patients. Once developed, 30% to 40% of patients with cirrhosis will suffer liver
      related death. NAFLD is considered the hepatic manifestation of the metabolic
      syndrome. Recent findings linking the components of metabolic syndrome with NAFLD
      and the progression to nonalcoholic steatohepatitis will be reviewed; in
      particular, the role of visceral adipose tissue, insulin resistance,
      adipocytokines, oxidative stress and diminished antioxidants within the liver in
      the exacerbation of these conditions. It is now widely accepted that non-hepatic
      mechanisms are largely responsible for the development of insulin resistance,
      which causes hepatic steatosis. Insulin resistance, a key feature of metabolic
      syndrome, is crucial for NASH development. We have a classical chicken-egg
      problem: insulin resistance causes hepatic steatosis or vice-versa? A possible
      sequence of the pathogenetic events is the following: increased free fatty acid
      supply - increased de novo lipogenesis - triglyceride and VLDL overproduction -
      atherogenic dyslipidemia- oxidative stress (lipid oxidation and peroxidation) -
      exhaustion of antioxidant defense system- "Tsunami" of inflammatory cytokines-
      fibrosis- carcinogenesis. Given the strong association of NAFLD with metabolic
      syndrome, early recognition, assessment and management are essential. The
      management emphasizes weight reduction and attention to global cardiometabolic
      risk factors, similar to recommendations for management of the elements of
      metabolic syndrome.

PMID- 21071305
TI  - [Non-alcoholic steatosis/steatohepatitis -- 2010].
AB  - Non-alcoholic steatosis/steatohepatitis is the most common etiology of abnormal
      liver function tests. Authors review the etiology, pathomechanism and clinical
      signs. Possibilities of the diagnosis are also summarized. There is an increasing
      need to find non-invasive biomarkers (TNF-alpha, adiponektin, end product of
      lipid peroxidation, cytokeratin-18, hyaluronic acid), score systems (Fibrotest,
      APRI), methods (Fibroscan), which would detect the progression of the disease,
      the development of inflammation and fibrosis. There is no proven specific
      therapy; the aim is the elimination of provoking factors (weight loss), treatment
      of diabetes mellitus and hyperlipidemia. Besides, liver protection (antioxidants)
      is important, as well.

PMID- 21071307
TI  - [Non-invasive fibrosis assessment in chronic hepatitis C: aspartate
      aminotransferase to platelet ratio index (APRI) and transient elastography
      (FibroScan)].
AB  - Although liver biopsy is the gold standard for the diagnosis of liver disease,
      non-invasive tests may also play a role in the evaluation of liver fibrosis.
      Authors studied two fibrosis markers, aspartate-aminotransferase / platelet ratio
      index (APRI) and liver stiffness (LS) measurement to assess fibrosis in different
      forms of chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: out of
      119 HCV-infected patients 75 had biopsy-proven chronic hepatitis C, 24 had HCV
      cirrhosis, 20 individuals were symptom-free HCV-carriers with persistently normal
      alanine-aminotransferase and 30 healthy blood donors served as controls. Wai's
      APRI score was calculated from aspartate-aminotransferase and platelet number.
      For LS measurement transient elastography (FibroScan) was applied. METAVIR
      fibrosis score was determined by liver biopsy. RESULTS: In patients with chronic
      hepatitis C infection both fibrosis markers were significantly elevated comparing
      to normal controls and the markers were the highest in HCV-associated cirrhosis.
      Values of symptom-free HCV-carriers corresponded to those obtained from healthy
      controls. Both APRI and LS results correlated with the METAVIR score. LS
      identified fibrosis better than APRI. Using a novel sequential algorithm that
      comprises APRI and LS for assessment of fibrosis, 47.8% of HCV patients did not
      need biopsy for diagnosing significant (F>=2) fibrosis. CONCLUSION: both fibrosis
      markers, particularly in combination, may represent a useful option in the
      noninvasive assessment of fibrosis in HCV infection.

PMID- 21071308
TI  - [Choice of surgical strategy for colorectal liver metastases depending on
      clinical and pathological response to neoadjuvant chemo- and targeted therapy].
AB  - Surgical strategy of colorectal liver metastases depends on clinical and
      pathological response to neoadjuvant chemo- and target therapy. Recently,
      surgical treatment of advanced colorectal cancer appears as an everyday challenge
      for surgeons and oncologists. The new oncologic procedures invented last years
      led to significant therapeutic improvement. Combination of neoadjuvant
      chemotherapy with biological answer modifiers increased greatly the clinical
      response rate given to cytoreductive therapy. Due to these facts the complete
      disappearance of liver metastases can be observed more and more frequently after
      2000. Literature of metastasis surgery clarified the exact difference between
      clinical and pathological response, at the same time exact criteria of the
      connections between two responses have been set. In complex treatment of
      colorectal liver metastases complete pathological response became the end point
      of treatment. AIMS AND METHODS: Between January, 2009 and August, 2010, 39
      patients with originally non resectable liver metastases (colorectal cancer
      origin) have been studied. All patients were treated by neoadjuvant chemo- and
      targeted therapy before the resection of liver. RESULTS: Complete pathological
      response has been observed in 3 patients, major pathological response (necrosis:
      >50%) in 11 patients, minor pathological answer (necrosis <50%) in 22 patients
      and finally no necrosis at all in 3 patients. CONCLUSIONS: Complete pathological
      response can be regarded as the final goal of neoadjuvant targeted therapy.
      Pathological response seems to be the most important prognostic factor which
      reflects long-term survival after the R0 resection of liver metastases. Complete
      disappearance of liver metastases is an undesirable side effect of oncological
      therapy, which causes difficulties during surgical intervention. In this term the
      overtreatment of patients resulting in a disappearance of metastases should be
      avoided. Multidisciplinary team is responsible for the indication of resection of
      liver metastases in time before their disappearance.

PMID- 21071310
TI  - Pharmacy in virtual environments: Insight and experiences from the Academies.

PMID- 21071311
TI  - National estimates and predictors of prescription medication sample use in the
      United States, 1999-2005.
AB  - OBJECTIVES: To determine the prevalence of free medication sample use in the
      United States and analyze the effects of socioeconomic status and drug safety
      actions. DESIGN: Cross-sectional study. SETTING: United States from 1999 to 2005.
      PARTICIPANTS: Survey respondents representative of the civilian
      noninstitutionalized population. INTERVENTION: Analysis of data from the Medical
      Expenditure Panel Survey, a nationally representative longitudinal household
      survey. MAIN OUTCOME MEASURES: Identification of a medication as being provided
      as a sample at least once during a study year. RESULTS: An annual average of 5.1%
      (range 4.4% in 2005 to 5.8% in 2002) of all prescription medications were
      provided as a sample at least once during a year, with 18.3% of all Americans who
      received at least one prescription drug receiving at least one drug as a sample.
      On multivariate analysis, sample use was greater among young (18-30 years) non
      Hispanic whites and the uninsured but had minimal independent association with
      income. The proportion of sample use among users of hormone replacement therapy
      and cyclooxygenase-2 inhibitors remained relatively constant even as total use of
      these drugs declined after Food and Drug Administration regulatory action.
      CONCLUSION: Use of medication samples is common in the U.S. population. After
      adjusting for health insurance, sample use was not associated with income and
      samples were less frequently provided to racial/ethnic minorities and to the
      elderly. The putative economic benefits of free samples do not appear to go to
      patients with the greatest financial need. Drug regulatory actions did not have a
      disproportionate effect on provision of drugs as samples.

PMID- 21071312
TI  - Identifying characteristics that allow pharmacy technicians to assume
      unconventional roles in the pharmacy.
AB  - OBJECTIVE: To identify aspects of pharmacy technicians' experience, training,
      practice setting, and location that influence whether technicians undertook roles
      traditionally performed by pharmacists. DESIGN: Descriptive, nonexperimental,
      cross-sectional study. SETTING: North Dakota in 2005. PATIENTS: All 456 pharmacy
      technicians registered in North Dakota (response rate 42.1% [n = 192]) actively
      working in a pharmacy-related practice setting. INTERVENTION: A survey was
      developed based on workforce studies of pharmacists and pharmacy technicians. The
      survey asked technicians to report demographic characteristics, education,
      experience, pharmacy setting, and community practice size. Respondents also were
      asked to identify whether they routinely performed specific tasks in the
      pharmacy, some of which are not typically performed by technicians. MAIN OUTCOME
      MEASURES: Eight "unconventional" tasks performed by technicians were selected as
      the focus of the analysis: compounding oral medications under the supervision of
      a pharmacist, compounding topical medications under pharmacist supervision,
      preparing third-party billing, requesting a refill authorization from a
      prescriber, taking patient medication history information, ordering stock from a
      wholesaler, taking new prescriptions over the telephone, and counseling patients
      on nonprescription medications. RESULTS: For each task, a binary logit model was
      used to identify the characteristics that significantly affected whether
      technicians performed a task. The practice setting was the most pervasive
      determinant of whether technicians performed specific tasks. Educational
      background and certification played a secondary role in influencing whether
      technicians performed each of these tasks. CONCLUSION: Pharmacy technicians are
      able to take on a larger role in pharmacy practice. However, technicians'
      abilities to fill these expanded roles may be limited and depend on various
      factors, including practice setting, acceptance by pharmacists, and technician
      experience.

PMID- 21071313
TI  - Effect of limited transportation on medication adherence in patients with
      epilepsy.
AB  - OBJECTIVE: To determine whether limited transportation affects medication
      adherence in patients with epilepsy. DESIGN: Descriptive, nonexperimental, cross
      sectional study. SETTING: United States and worldwide, February to April 2007.
      PATIENTS: 143 patients with epilepsy. INTERVENTION: A 22-item survey was
      developed to ask patients with epilepsy or their caregivers about the impact of
      limited transportation on adherence with medications. The survey was placed on
      Zoomerang.com. An invitation to participate in the survey was sent via e-mail to
      members of the Epilepsy.com website, and an invitation with a link to the survey
      was placed on Epilepsy.com. MAIN OUTCOME MEASURES: Whether patients with epilepsy
      have difficulty picking up prescriptions on time because of transportation
      problems and whether they felt they would miss fewer doses if transportation was
      not an issue. RESULTS: 143 individuals with epilepsy completed part or all of the
      survey. Of patients who were unable to drive, 45% reported that fewer doses would
      be missed if transportation was not a problem. Patients who were unable to drive
      had an odds ratio of 4.2 (P < 0.0001) of being unable to get medications on time.
      No differences were observed in the number of patients missing prescription
      medications associated with availability of insurance, use of mail service
      pharmacies, or population size of patients' area of residence. Ability to drive
      and distance to the pharmacy were the only factors associated with nonadherence.
      CONCLUSION: Limited transportation may be a factor in poor medication adherence
      in patients with epilepsy.

PMID- 21071314
TI  - Relationship between attitudes toward mental illness and provision of pharmacy
      services.
AB  - OBJECTIVES: To compare how community pharmacists felt they and other health
      professionals perceived individuals with depression and schizophrenia and whether
      pharmacists' attitudes and other factors affected willingness to provide services
      to patients with mental illness. SETTING: Northeastern United States in summer
      2006. PARTICIPANTS: Pharmacists at 750 community pharmacies. INTERVENTION: A
      survey was mailed to the community pharmacies, which were randomly selected from
      a list obtained from a state board of pharmacy in the northeastern United States.
      MAIN OUTCOME MEASURES: Pharmacist attitudes toward individuals with schizophrenia
      and depression and willingness to provide pharmacy services to patients with
      mental illness. RESULTS: 292 surveys were completed (response rate 38.9%). The
      pharmacists surveyed felt that they had more positive attitudes toward
      individuals with depression and schizophrenia compared with other pharmacists (P
      =<=0.01). Compared with physicians, pharmacists perceived themselves as having
      less negative attitudes toward those with depression (P =<=0.001) but greater
      negative attitudes toward individuals with schizophrenia (P =<=.05). More
      pharmacists were willing to provide services to those with asthma than those with
      mental illness (P =<=0.001). Pharmacists were more likely to provide services to
      patients with mental illness if they had fewer negative attitudes for those with
      depression or schizophrenia and placed a greater value on counseling patients (P
      =<=0.001). Minority pharmacists were more willing to provide services to patients
      with mental illness. CONCLUSION: Community pharmacists have more negative views
      of schizophrenia than depression and felt that they perceived those with
      schizophrenia more negatively than physicians. Our findings suggest two ways to
      improve community pharmacist willingness to provide services to patients with
      mental illness: reduce negative attitudes toward patients with mental illness and
      increase pharmacists' perceived value of counseling patients.

PMID- 21071315
TI  - Analysis of pharmacy-centric blogs: Types, discourse themes, and issues.
AB  - OBJECTIVES: To determine types of pharmacy blogs in existence, themes of
      discourse on pharmacy blogs, and impressions of the profession generated by
      pharmacy blogs. DESIGN: Descriptive, qualitative, cross-sectional study. SETTING:
      Weblogs (blogs) on the World Wide Web in July 2009. PARTICIPANTS: Not applicable;
      pharmacy-centric blogs were analyzed. INTERVENTION: Qualitative research methods
      were used to form categories and assign pharmacy-centric blogs to appropriate
      categories. Thematic analysis was used to study the discourse of blogs in the
      personal views category. Finally, blogs in the personal views category were
      analyzed further to determine what type of impression (positive, negative, or
      neutral) they gave the reader. MAIN OUTCOME MEASURES: Categories, themes, and
      impressions of blogs, as determined by analysis. RESULTS: 136 blogs met study
      criteria. Seven main categories of pharmacy blogs emerged from the study. The
      majority of blogs were assigned to the news (n = 44) and personal views (n = 38)
      categories. Thematic analysis of blogs in the personal views category revealed 11
      different themes. The top four blog post themes were issues with patients (n =
      30), personal lives (n = 29), working conditions/issues (n = 20), and issues with
      other professionals (n = 19). A total of 24 (63%) blogs in the personal views
      category were judged as promoting a negative impression of pharmacists and/or the
      profession. CONCLUSION: The pharmacy blogosphere contains a variety of blog
      types. Most of these blogs studied were useful information resources for those in
      or considering the profession. However, a considerable number of pharmacy blogs
      contained derogatory posts regarding patients, other health care professionals,
      and/or the author's occupation as a pharmacist. Blogs such as these tend to
      generate a negative impression of pharmacy to the reader. The opportunity exists
      for pharmacists and pharmacy educators to use social media applications such as
      blogs to educate new pharmacists and advance the profession.

PMID- 21071316
TI  - Medication management in North Carolina elementary schools: Are pharmacists
      involved?
AB  - OBJECTIVE: To determine the extent of pharmacist use in medication management,
      roles of school nurses, and use of other health care providers at elementary
      schools in North Carolina. METHODS: Prospective survey of 153 (130 public and 23
      private) elementary schools in four counties of North Carolina. A 21-question
      survey was e-mailed to the head administrator of each school (e.g., principal,
      headmaster) containing a Qualtrics survey link. Questions were designed to elicit
      information on school policies and procedures for medication management and use
      of health care providers, including pharmacists, in the schools. Responses were
      collected during a 2-month period. RESULTS: Representatives from 29 schools
      participated in the survey (19% response rate). All 29 schools reported having a
      school policy regarding medication administration during school hours. Of those,
      27 schools reported consulting with nurses on their policies. Only 1 of 27
      respondents reported consulting with pharmacists on medication management
      policies. The majority of the respondents (93.1%) stated that administrative
      staff was responsible for medication administration at the schools. CONCLUSION:
      Use of pharmacists in creating and reviewing policies for schools and actual
      medication management at schools was extremely low. The findings in this study
      reinforce the findings in previous studies that pharmacists are not being used
      and are not a major presence in elementary school health.

PMID- 21071317
TI  - Needs assessment analysis for vitamin K antagonist anticoagulation in the
      resource-constrained setting of Eldoret, Kenya.
AB  - OBJECTIVES: To assess the frequency of indications for vitamin K antagonist (VKA)
      therapy in the inpatient and outpatient setting in Eldoret, Kenya, and to
      describe the strategies used for managing these conditions. METHODS: All
      inpatient admissions during a 1.5-month period were prospectively assessed for
      any indications for VKA therapy by clinical pharmacy staff. For the outpatient
      assessment, the files of all patients receiving care in the outpatient adult
      cardiology clinic within the previous 6 months were identified and evaluated for
      indications for VKA therapy. For patients identified with an indication for VKA
      therapy, additional information was collected, including the VKA indication,
      pharmacologic management, and any other risk-modifying conditions. RESULTS: In
      the primary analysis, 20 of the 554 patients admitted to the public adult wards
      (3.61% [95% CI 2.14-5.08]) were candidates for VKA therapy. Of the 168 outpatient
      cardiology clinic charts reviewed, 72 patients (42.8% [37.96-47.76]) had
      indications for VKA therapy. In the secondary analysis, 70% of the inpatient
      population and 93% of the outpatient population received suboptimal VKA therapy.
      Of these patients in need of VKA therapy, 53.3% were on aspirin therapy only and
      33.7% were not receiving any pharmacologic therapy. CONCLUSION: As developing
      countries begin to address the growing burden of chronic diseases, a commensurate
      focus on providing infrastructure for comprehensive cardiovascular care,
      including an organized VKA monitoring service, needs to occur.

PMID- 21071318
TI  - Antibiotic use for acute upper respiratory tract infections in a veteran
      population.
AB  - OBJECTIVE: To evaluate the effect of age, symptom duration, symptom presentation,
      presenting location, and type of acute upper respiratory tract infection (URI) on
      the receipt of inappropriate antibiotic prescriptions in adult patients. METHODS:
      A retrospective cross-sectional study was conducted within a U.S. Department of
      Veterans Affairs health system. A total of 500 adult patients with acute URI
      during a 1-year study period were randomly selected and evaluated for receipt of
      antibiotic prescriptions. Patients were excluded if they had an indication for
      antibiotics based on Centers for Disease Control and Prevention criteria,
      concomitant infection, or unreviewable patient record. Patients were grouped and
      compared by age, symptom duration, symptom presentation (purulence of
      secretions), presenting location, and type of URI. RESULTS: Overall, antibiotics
      were prescribed to 77% (219 of 283) of patients included in the study. Patients
      with purulent symptoms received a higher proportion of antibiotic prescriptions
      compared with those without purulent symptoms (P < 0.01). Patients seen in
      routine primary care received a lower proportion of antibiotic prescriptions
      compared with those seen in the emergency department or urgent care/primary care
      walk-in clinic (P < 0.01). No significant difference was observed in the
      proportion of antibiotic prescriptions based on symptom duration (P = 0.99) or
      age (P = 0.19). Patients with acute sinusitis or bronchitis received a higher
      proportion of antibiotics than those with acute pharyngitis or nonspecific URI (P
      < 0.01). CONCLUSION: Despite evidence-based practice guidelines for the rational
      use of antibiotics in patients with upper respiratory tract infections, these
      conditions are being treated inappropriately. Patient and provider factors play a
      role in the receipt of antibiotics. Further efforts, including those by
      pharmacists, are needed to improve the use of antibiotics for acute URI in adult
      patients.

PMID- 21071319
TI  - Continuing professional development training program among pharmacist preceptors
      and nonpreceptors.
AB  - OBJECTIVES: To administer, observe, and evaluate the effectiveness of a condensed
      continuing professional development (CPD) training program among chain community
      pharmacy preceptors and nonpreceptors in North Carolina. METHODS: 120 community
      preceptors and nonpreceptors affiliated with a large community chain pharmacy
      completed a 5-hour CPD program consisting of home study and live portions and
      were given pre- and postintervention surveys. The main outcome measures were
      knowledge and familiarity of CPD among community chain pharmacy preceptors and
      nonpreceptors, effectiveness of the condensed training program, and perceptions
      on implementing the CPD process after training. RESULTS: Before the educational
      activity, differences between participants were (1) the percent of women
      pharmacists (40% of preceptors and 65% of nonpreceptors) and (2) that preceptors
      were more likely to accomplish planned learning activities compared with
      nonpreceptors. Of 97 nonpreceptors and 23 preceptors trained, more than 90%
      reported being able to achieve the program objectives and responded positively to
      the survey questions and 100% indicated that the educational activity enhanced
      their knowledge and skill levels. At least 85% of participants responded that the
      program length was satisfactory. The postsurvey revealed that 87% of participants
      were at least moderately familiar with the concept of CPD. Of respondents, 83%
      indicated that they will implement CPD at their practice site. CONCLUSION: A
      condensed CPD program is efficient and effective in training community chain
      pharmacy preceptors and nonpreceptors. The majority of the pharmacists who
      responded indicated that they will implement CPD at their practice site after
      going through this program.

PMID- 21071320
TI  - Closer look at autism and the measles-mumps-rubella vaccine.
AB  - OBJECTIVE: To educate pharmacists regarding the hypothesis that the measles-mumps
      rubella (MMR) vaccine is linked to the development of autism. DATA SOURCES:
      Articles published from 1998 to 2009 were identified through electronic searches
      of Medline. STUDY SELECTION: Articles were included if they evaluated or reviewed
      a possible link between the MMR vaccine and autism or discussed MMR epidemiology,
      legal proceedings involving the MMR vaccine and autism, or health professionals'
      impact on immunization decisions. DATA SYNTHESIS: A total of 27 articles were
      identified. Of the articles, 74% (20 of 27) were included in the review because
      of their relevance to the study topic. CONCLUSION: The evidence presented does
      not show a causal relationship between the MMR vaccine and autism. Myths
      presented to potentially support any relationship between the MMR vaccine and
      autism have not been proven. Expert testimony refuting initial scientific
      theories has led to Supreme Court decisions that do not support a link between
      the MMR vaccine and autism. Pharmacists and all health care providers are
      responsible for informing and educating parents and families regarding this
      information so that they can make informed decisions about immunizations.

PMID- 21071321
TI  - Pseudotumor cerebri due to the potentiation of all-trans retinoic acid by
      voriconazole.
AB  - OBJECTIVE: To report an interaction between all-trans retinoic acid (ATRA) and
      voriconazole resulting in pseudotumor cerebri. SETTING: Hospital in Huntsville,
      AL, in November 2007.Patient description: 21-year-old black woman admitted to the
      hospital for fever in the setting of pancytopenia. CASE SUMMARY: The patient had
      been diagnosed with acute promyelocytic leukemia 5 months before admission and
      continued on ATRA throughout induction and two consolidation therapies.
      Voriconazole was started in view of persistent fever and pancytopenia despite
      adequate broad-spectrum antimicrobial therapy. On day 15 of voriconazole therapy,
      the patient complained of blurred vision, farsightedness, and dry skin with
      pruritus and was subsequently diagnosed with pseudotumor cerebri secondary to
      ATRA toxicity. All symptoms of pseudotumor cerebri resolved after discontinuation
      of ATRA. MAIN OUTCOME MEASURES: Not applicable. RESULTS: The development of
      pseudotumor cerebri after initiation of voriconazole may have been secondary to
      the inhibition of the cytochrome P450 (CYP) enzymes. The interaction may have led
      to changes in ATRA serum concentrations, thus contributing to the observed
      adverse drug reaction. CONCLUSION: To our knowledge, this is the first case
      report of pseudotumor cerebri in an adult patient secondary to metabolic
      inhibition of ATRA by voriconazole. This case illustrates the importance of
      monitoring for drug interactions when using medications metabolized via the CYP
      enzyme pathway.

PMID- 21071322
TI  - Pharmacy, social media, and health: Opportunity for impact.
AB  - OBJECTIVE: To discuss opportunities and challenges for pharmacists' use of social
      media to affect health care. DATA SOURCES: Not applicable. SUMMARY: Evolutions in
      social media (e.g., Facebook, Twitter, YouTube) are beginning to alter the way
      society communicates. These new applications promote openness, user-generated
      content, social networking, and collaboration. The technologies, along with
      patient behaviors and desires, are stimulating a move toward more open and
      transparent access to health information. Although social media applications can
      reach large audiences, they offer message-tailoring capabilities that can
      effectively target specific populations. Another powerful aspect of social media
      is that they facilitate the organization of people and distribution of content
      two necessary components of public health services. Although implementing health
      interventions via social media poses challenges, several examples exist that
      display the potential for pharmacists to use social media in health initiatives.
      CONCLUSION: Pharmacists have long played a role in educating patients on matters
      influencing health care. Social media offer several unique features that may be
      used to advance the role of pharmacy in health care initiatives. Public
      familiarity with social media, the economical nature of using social media, and
      the ability to disseminate information rapidly through social media make these
      new applications ideal for pharmacists wanting to provide innovative health care
      on both an individual and public level.

PMID- 21071323
TI  - Deeply discounted medications: Implications of generic prescription drug wars.
AB  - OBJECTIVE: To describe the history of generic prescription pricing programs at
      major pharmacy chains and their potential implications on prescribing, quality of
      care, and patient safety. DATA SOURCES: Publicly available generic prescription
      discount program drug lists as of May 1, 2009. SUMMARY: Fierce competition among
      major pharmacy chains such as Walgreens, CVS, and Walmart has led to a generic
      prescription pricing war with unclear public health implications. Introduced in
      2006, currently 7 of the 10 largest pharmacy chains advertise a version of a
      deeply discounted medication (DDM) program, accounting for more than 25,000
      locations nationally. By early 2008, almost 70 million Americans had used these
      programs. Although DDM programs lower drug costs for many patients, DDM
      formularies include potentially ineffective or harmful medications, have the
      potential to influence physician prescribing behavior, and may impair
      pharmacists' ability to review complete drug-dispensing records. CONCLUSION: DDMs
      are widespread but have the potential for unintended consequences on patients,
      providers, and the health care system. A systematic review of DDMs needs to
      evaluate the clinical, economic, and system-level implications of such programs.

PMID- 21071324
TI  - Longer-term implications of the generic prescription drug "price war".

PMID- 21071325
TI  - $4 generics: How low, how broad, and why patient engagement is priceless.

PMID- 21071326
TI  - Heroes of Pharmacy postscript: Ave atque vale.

PMID- 21071327
TI  - George Dilwin Coggeshall (1808-1891): First great American pharmacy school
      graduate.

PMID- 21071328
TI  - Influenza vaccination: Am I protected?

PMID- 21071329
TI  - New drugs: Sipuleucel-T, cabazitaxel, and collagenase clostridium histolyticum.

PMID- 21071330
TI  - Science snippets. Atrial fibrillation prophylaxis, disparity in MTM services
      eligibility, and point-of-care risk screening.

PMID- 21071332
TI  - Biomarkers as prognostic factors in endometrial cancer.
AB  - Endometrial cancer is the most common gynecologic malignancy in more developed
      countries. Approximately 75% of cases are diagnosed at an early stage with a
      tumor confined to the uterine corpus. Although most patients are cured by surgery
      alone, about 15-20% with no signs of locally advanced or metastatic disease at
      primary treatment recurs, with limited responsiveness to systemic therapy. The
      most common basis for determining the risk of recurrent disease has been
      classification of endometrial cancers into two subtypes. Type I, associated with
      a good prognosis and endometrioid histology and type II, associated with a poor
      prognosis and non-endometrioid histology. This review will focus primarily on the
      molecular biomarkers that have supported the dualistic model of endometrial
      carcinoma and help determine which patients would benefit from either adjuvant
      therapy or more aggressive primary treatment.

PMID- 21071331
TI  - A multicenter open-label study to assess the safety of a new formulation of BLP25
      liposome vaccine in patients with unresectable stage III non-small-cell lung
      cancer.
AB  - INTRODUCTION: BLP25 liposome vaccine (L-BLP25) is an innovative therapeutic
      cancer vaccine designed to induce an immune response resulting in elimination of
      tumor cells expressing the MUC1 antigen, which is overexpressed in non-small-cell
      lung cancer (NSCLC). Manufacturing modifications have produced subtle changes to
      the lipid A acyl chain composition of L-BLP25. This open-label phase II study was
      conducted to evaluate the safety of the new formulation in patients with
      unresectable stage IIIA/IIIB NSCLC. PATIENTS AND METHODS: Twenty-two patients
      received L-BLP25 1000 ug every week for 8 weeks plus best supportive care.
      Maintenance vaccinations were given every 6 weeks, commencing at week 13, until
      disease progression. RESULTS: Median treatment duration was 9.9 months (range, 1
      30 months), 9 patients remain on treatment, and 8 have received treatment for > 2
      years. Fifteen patients (68%) had adverse events considered to be related to L
      BLP25: these were all grade 1/2, except for 1 grade 3 event (pneumonia). The most
      common adverse events were injection-site reactions (bruising [23%], erythema
      [18%], pain [14%], fatigue [18%], and influenza-like illness [14%]). After a
      median follow-up of 26.7 months, the 1-year survival rate was 82% (95% CI, 66%
      98%), and the 2-year survival rate was 64% (95% CI, 44%-84%). CONCLUSION: The
      results suggest that the new formulation of L-BLP25 has a safety profile similar
      to the original formulation and is safe to use in the phase III clinical
      development program.

PMID- 21071333
TI  - Cysteine peptidases and their inhibitors in breast and genital cancer.
AB  - Cysteine proteinases and their inhibitors probably play the main role in
      carcinogenesis and metastasis. The metastasis process need external proteolytic
      activities that pass several barriers which are membranous structures of the
      connective tissue which includes, the basement membrane of blood vessels.
      Activities of the proteinases are regulated by endogenous inhibitors and
      activators. The imbalance between cysteine proteinases and cystatins seems to be
      associated with an increase in metastatic potential in some tumors. It has also
      been reported that proteinase inhibitors, specific antibodies for these enzymes
      and inhibition of the urokinase receptor may prevent cancer cell invasion. Some
      proteinase inhibitor could serve as agents for cancer treatment.

PMID- 21071334
TI  - Assessment of the transcription levels for the complement activation control
      system in eutopic endometrium in women with two or more consecutive miscarriages
      of unknown etiology.
AB  - Human endometrium, deciuda and placenta have been shown to express factors that
      inhibit the complement activation cascade - decay-accelerating factor (DAF),
      membrane cofactor protein (MCP) and the C3 complement component. In the following
      study we have analyzed the transcripts levels for DAF, MCP and heparin-binding
      epidermal growth factor-like growth factor (HB-EGF), the C3 complement component
      and receptor for vascular endothelial growth factor (VEGFR1) as markers of
      endometrial unbalance between factors activating the complement system in women
      with consecutive miscarriages. Study enrolled 30 women with at least two
      consecutive miscarriages, and 19 healthly women, that comprised the control
      group. RNA was isolated from endometrial samples. Transcripts levels of DAF and
      MCP was higher in women with consecutive miscarriages compared to controls, 0.78
      vs 5.08 (p<0.001) and 0.25 vs 0.17 (p=0.001) respectively. In consecutive
      miscarriages group, DAF and MCP expression was correlated with the C3 expression,
      with r=0.60; p<0.001 and r= 0.40; p=0.03 respectively. Correlation between DAF
      and C3 was also noted in controls, 0.70; p=0.001. In women with two or more
      consecutive miscarriages the analysis proved higher expression of genes that
      encode proteins that inhibit the complement cascade. Further studies are needed
      to confirm that this might be a reaction to increased presence of the complement
      factors, which like C3 that are synthesized in the endometrium.

PMID- 21071335
TI  - Assessment of S100 protein expression in the epididymis of juvenile and adult
      European bison.
AB  - In our study, we decided to compare S100 protein expression in the material
      obtained from the epididymes of 5- and 12-month-old calves, and adult European
      bison, and to detect any differences in S100 expression according to the animal
      age and size of the organ examined. We used the epididymes obtained from 6 adult
      European bison aged 6-12 years, from 6 at the age of 12 months and 6 calves aged
      5 months. Immunocytochemical reactions were performed using the avidin
      biotinylated-peroxidase (ABC) technique according to HSU. Specific polyclonal
      rabbit antiserum against bovine S100 protein (Bio Genex Laboratories) at a
      dilution at 1:400 was applied. We found the expression of S100 protein in
      endothelial cells of arteries, veins and lymphatic vessels in all the study
      animals. At the same time, we found no differences in the expression of S100
      protein in vascular endothelial cells. Our observations seem to indicate that
      S100 expression in endothelial cells of European bison epididymis is not
      correlated with age or maturity of the organ tested. We found S100 protein in
      smooth muscle cells of arteries and veins in all European bison specimens
      examined. Interestingly in the current study, in young 5-month-old sexually
      immature European bison specimens we observed weaker expression of S100 protein
      in smooth muscle cells of small vessels as compared to the same cell type both in
      large vessels in these animals and in small vessels in adult specimens.

PMID- 21071336
TI  - The connective tissue response to Ti, NiCr and AgPd alloys.
AB  - The aim of the study was to compare the connective tissue response of Lewis rats
      to Ti, NiCr and AgPd alloys. It was found that implants were covered by collagen
      rich, well vascularized capsules. Titanium was covered by the thinnest capsule
      (57 +/- 20 MUm) and AgPd alloy was covered by the thickest capsule (239 +/- 50
      MUm). The PCNA+ cell prevalence in the capsules was lower for titanium than for
      AgPd and NiCr. Mast cells formed a gradient to a depth of 1200 MUm only for
      titanium implants. Cells with brown to black silver granules in the cytoplasm
      were observed close to AgPd implants. The results suggest that titanium implants
      induce a weaker connective tissue response than implants made from NiCr and AgPd
      alloys.

PMID- 21071337
TI  - Evaluation of TLR4 expression and chosen parameters of oxidative-antioxidative
      balance in young children with food allergy.
AB  - The authors evaluated mRNA TLR4 expression on neutrophils and the chosen
      parameters of oxidative-antioxidative balance in blood of 35 children with food
      allergy (17 of them with IgE-dependent allergy and 18 with IgE-independent
      allergy) and 15 healthy children without any allergy. The age of these children
      ranged from 1 to 36 months. Children with food allergy in comparison with healthy
      children were found to have lower mRNA TLR4 expression, higher average value of
      chemiluminescence (CL) and its increase after stimulation by fMLP, PMA and OZ as
      well as lower TAS values. Disturbances of oxidative-antioxidative balance were
      found in children with food allergy. We suggest that natural immunity is involved
      in the development of food allergy mechanisms. Moreover, chemiluminescence can be
      used as an additional diagnostic test.

PMID- 21071338
TI  - Lysosomal exoglycosidases in serum and urine of patients with pancreatic
      adenocarcinoma.
AB  - Lysosomal exoglycosidases: N-acetyl-beta-D-hexosaminidase (HEX), beta-D
      galactosidase (GAL), alpha-L-fucosidase (FUC) and alpha-D-mannosidase (MAN)
      modify oligosaccharide chains of glycoconjugates in endoplasmatic reticulum
      and/or Golgi apparatus and degrade them in lysosomes. In acid environment of
      lysosome, exoglycosidases degrade oligosaccharide chains of glycoproteins,
      glycolipids and glycosaminoglycans by eliminating single sugars from the edges of
      oligosaccharide chains. Neoplasms change biochemical processes in tissues and may
      significantly change the activity of many enzymes including the activity of
      lysosomal exoglycosidasses in serum and urine of persons with neoplasmatic
      diseases. The aim of the present paper was evaluation the activity of HEX, GAL,
      FUC and MAN in serum and urine of patients with pancreatic adenocarcinoma. Serum
      and urine samples were collected from 15 patients with adenocarcinoma of the
      pancreas and 15 healthy persons. The activity of lysosomal exoglycosidases was
      determined by the method of Marciniak et al. adapted to serum and urine of
      patients with adenocarcinoma of the pancreas. Our results indicate significant
      decrease in activity of GAL (p=0.037) in serum of patients with pancreatic
      adenocarcinoma, significant increase in activity of HEX (p<0.001) and FUC
      (p=0.027) in serum, and HEX (p=0.003) in urine, as well as significant decrease
      of FUC (p=0.016) and MAN (p=0.029) in urine o patients with adenocarcinoma of the
      pancreas, in comparison to the control group. Increase in activity of some
      lysosomal enzymes in serum and urine of pancreatic adenocarcinoma patients, may
      indicate on destruction of pancreatic tissue by pancreatic adenocarcinoma.
      Determination of the HEX, GAL, FUC and MAN in serum and urine may be useful in
      diagnostics of pancreatic adenocarcinoma.

PMID- 21071339
TI  - Bilateral sweat tests with two different methods as a part of cystic fibrosis
      newborn screening (CF NBS) protocol and additional quality control.
AB  - Infants with positive CF newborn screening (NBS) results are called to a CF
      Centre for verification. Those, in whom the sweat test is elevated, undergo
      further medical procedures. The aim of our study was to evaluate the
      applicability of Nanoduct - a new system measuring sweat conductivity and giving
      immediate results in a CF NBS protocol. Measurements with Nanoduct were compared
      with the classic pilocarpine method. During 3 years 487 infants from CF NBS had
      both sweat tests performed on the same day, at the same CF centre. CF infants had
      a mean conductivity of 99.8 +/- 1 8.8 mmol/L and a mean chloride concentration of
      74.0 +/- 18.4 mmol/L. Non-CF infants values were 29.8 +/- 7.7 mmol/L and 19.2 +/-
      6.6 mmol/L respectively. A good correlation between both tests was found (95%
      confidence level (CI); r=0.87). The optimal cut off, based on follow up
      experience of screened children, for conductivity tests was 50 mmol/L and for
      chloride concentration was 34 mmol/L (no lost CF, 11 false positive) with 100%
      sensitivity and 97.5 % specificity. In conclusion Nanoduct is a very useful and
      reliable tool in CF NBS protocol, allowing more time efficient organization of
      the diagnostic and training procedures. Simultaneous bilateral sweat testing with
      two different methods (concentration and conductivity) provides an extra quality
      control system.

PMID- 21071340
TI  - Total matrix metalloproteinase-8 serum levels in patients labouring preterm and
      patients with threatened preterm delivery.
AB  - Preterm labour and prematurity are still a main cause of perinatal morbidity
      nowadays. The aim of our study was to assess the role of MMP-8 as a predictive
      marker of preterm delivery. Four groups of patients were involved to the study: I
      - pregnant women at 24-34 weeks of gestation with any symptoms of threatened
      preterm labour; II - threatened preterm labour patients between 24-34 weeks of
      gestation; III - preterm vaginal delivery patients; IV - healthy term vaginal
      delivery patients. Serum concentration of total MMP-8 was measured using two
      enzyme-linked immunosorbent assays. There were no significant differences in the
      median concentrations of total MMP-8 between physiological pregnancy and
      threatened preterm labour patients with existing uterine contractility. No
      significant differences of total MMP-8 were either found between healthy term and
      preterm labouring patients. The studies on a larger population are needed to
      reject the hypothesis that preterm labour is connected with increased MMP-8
      plasma concentrations of women in preterm labour and threatened preterm delivery.

PMID- 21071341
TI  - Ultrastructural changes in the developing chicken cornea following caffeine
      administration.
AB  - Caffeine is one of the most frequently consumed psychoactive substances. It has
      been known for many years that caffeine at high concentrations exerts harmful
      effects on both women's and laboratory animals' fertility, moreover it may impair
      normal development of many organs in the prenatal period. So far there have been
      few studies performed that demonstrate teratogenic effects of caffeine on
      structures of the developing eye, particularly the cornea. The aim of the study
      was to show ultrastructural changes in the developing cornea, as the effect of
      caffeine administration to chicken embryos. The experimental materials were 26
      chicken embryos from incubated breeding eggs. Eggs were divided into two groups:
      control (n=30) in which Ringer liquid was administrated, and experimental (n=30)
      in which teratogenic dose of caffeine 3.5mg/egg was given. In 36th hour of
      incubation solutions were given with cannula through hole in an egg shell
      directly onto amniotic membrane. After closing the hole with a glass plate and
      paraffine, eggs were put back to incubator. In 10th and 19th day of incubation
      corneas were taken for morphological analysis with a use of electron microscopy.
      Administration of caffeine during chicken development causes changes of collagen
      fibers of Bowman's membrane patterns and of the corneal stroma but it also
      changes proportion of amount of collagen fibers and of the stromal cells.

PMID- 21071342
TI  - Doxorubicin-induced F-actin reorganization in cofilin-1 (nonmuscle) down
      regulated CHO AA8 cells.
AB  - The actin cytoskeleton plays an important role in many cellular processes,
      including cell mortality, mitosis, cytokinesis, intracellular transport,
      endocytosis and secretion but also is involved in gene transcription. The
      dynamics of the actin cytoskeleton is controlled by different classes of actin
      binding proteins (ABPs) which regulate the polymerization of actin filaments. In
      this report we used siRNA against cofilin-1 (nonmuscle) to demonstrate the effect
      of cofilin on the nuclear and cytoplasmic actin pools in CHO AA8 cells after
      exposition to various concentrations of doxorubicin. The immunofluorescence
      studies showed doxorubicin dose dependent tendency to formation the
      multinucleated giant cells, but also the increase of fluorescence intensity of
      cofilin in nuclei of untransfected cells. Induction of cell death with
      doxorubicin treatment in untransfected cells revealed both mitotic catastrophe
      (in both lower and higher doxorubicin doses) and apoptosis (mostly in higher
      doxorubicin doses), whereas among cofilin-1 down-regulated cells we observed only
      mitotic catastrophe. The results suggest that cofilin has apoptosis-inducing
      ability and that mitotic catastrophe is independent from F-actin content in cell
      nucleus. In this point of view we conclude that different mechanisms of chromatin
      reorganization are involved in these two processes. Moreover, we suppose that
      apoptosis and mitotic catastrophe are independent from each other.

PMID- 21071343
TI  - An immunohistochemical study of the pancreatic endocrine cells of the ddN mouse.
AB  - The regional distribution and frequency of the pancreatic endocrine cells in the
      ddN mouse were studied using specific antisera against insulin, glucagon,
      somatostatin and human pancreatic polypeptide (hPP). In the pancreatic islets,
      most of insulin-immunoreactive (IR) cells were located in the central region, and
      glucagon-, somatostatin and hPP-IR cells were located in the peripheral region
      regardless of the lobe. In the splenic part, glucagon-IR cells were also located
      in the central regions, and more numerous somatostatin-IR cells were detected in
      the central regions as compared with the duo-denal part. hPP-IR cells were
      restricted to the peripheral regions in both lobes but more numerous cells were
      detected in the duodenal portion. In the exocrine parenchyma of the splenic lobe,
      only insulin- and glucagon-IR cells were detected but all four kinds of IR cells
      were observed in the duodenal portion. In addition, insulin and hPP-IR cells were
      also demonstrated in the pancreatic duct regions. In conclusion, some strain
      dependent characteristic distributional patterns of pancreatic endocrine cells
      were found in the ddN mouse with somewhat different distributional patterns
      between the two pancreatic lobes.

PMID- 21071344
TI  - Immunohistochemical detection of dopamine D2 receptors in human pituitary
      adenomas.
AB  - Thirty one pituitary adenomas and 3 samples of peritumoral anterior pituitary
      tissue were immunostained with an antibody raised against dopamine D2 receptor
      protein. The positive reactions were found in cell cytoplasm, a subpopulation of
      cell nuclei and the intratumoral blood vessels walls. As expected, the positive
      immunostaining was shown in cytoplasm and/or cell nuclei of all examined
      prolactinomas (7/7). In acromegaly the positive D2 staining occurred in 5/7
      samples, in gonadotropinomas in 6/8 and in plurihormonal adenomas 2/4. The lowest
      expression was observed in corticotropinomas (1/5). These findings corroborate
      with the well known efficacy of D2 agonists in the treatment of prolactinomas and
      somatotropinomas, and support the rationale of the therapeutic trials with these
      compounds in gonadotropinomas. Moreover, the presence of D2 receptors in
      intratumoral blood vessels walls constitutes the possibility of the anti
      angiogenic action of D2 agonists in pituitary adenomas.

PMID- 21071345
TI  - Usefulness and efficiency of formalin-fixed paraffin-embedded specimens from
      laryngeal squamous cell carcinoma in HPV detection by IHC and PCR/DEIA.
AB  - The use of formalin-fixed paraffin-embedded (FFPE) tissues for HPV DNA detection
      by PCR from biopsy materials is not entirely clear in retrospective studies. The
      aim of our study was to evaluate the usefulness and efficiency of FFPE tissues
      from laryngeal cancer (LSCC) in HPV detection by immunohistochemistry reaction
      (IHC) and PCR-DNA enzyme immunoassay method (PCR/DEIA) and to compare with HPV
      detection from DFT. HPV-DNA was amplified from 54 FFPE tissues from LSCC
      specimens by the short PCR fragment (SPF10) primer set using PCR/DNA method and
      monoclonal anti Human Papillomavirus antibodies in IHC. In the same patients 54
      specimens were collected and immediately deep-frozen and stored at (-70 degrees
      C) to (-80 degrees C). All the FFPE and deep-frozen tissue (DFT) specimens were
      positive for beta-globin amplification. HPV was detected by two methods (SPF10
      PCR/DEIA and IHC) in 14 (25.92%) out of 54 specimens from FFPE. Significant
      differences were found between the HPV detection using PCR/DEIA method and IHC
      method in FFPE tissues. The comparative analysis of the 54 samples after assuming
      PCR method in FFPE tissues showed accuracy of 92.6%, sensitivity of 90.5% and
      specificity of 93.9%. The FFPE tissues method has high sensitivity, specificity
      and accuracy when used to detect HPV DNA by PCR reaction and it is comparable to
      DFT results. DNA quality of FFPE samples is adequate and it can be used in HPV
      DNA detection and in retrospective studies on LSCC.

PMID- 21071346
TI  - Type II muscle fibers atrophy associated with silent corticotroph adenoma in a
      dog.
AB  - The Silent Corticotroph Adenoma (SCA) is a pituitary adenoma variant
      characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH) and
      related peptides, without the clinical signs of Cushing's disease. SCA has been
      postulated to either secrete structurally abnormal ACTH that is inactive but
      detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH
      intermittently or at low levels continuously. Excess of ACTH has been associated
      to type II muscle atrophy. We describe a case of type II muscle fibers atrophy
      associated with silent corticotroph adenoma in a dog. The dog showed moderate to
      severe proximal muscle wasting and weakness with normal levels of muscle
      associated enzymes. In the limb muscle biopsies, type II fibers were uniformly
      smaller than type I fibers. In temporalis muscles, there were few atrophic
      fibers, and several irregular areas of loss of enzymatic activity observed in
      NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and
      immunohistochemical analysis demonstrated the presence of cytoplasmic
      immunoreactivity for ACTH. The muscle atrophy was considered to be related to an
      excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals
      could help to understand the mechanism of similar diseases in human has well.

PMID- 21071347
TI  - The TRAF2 and TRAF6 expression in myomas and myometrium of women in reproduction
      and perimenopausal age.
AB  - Uterine myomas represent one of the most common female diseases. Uterine myomas
      or fibromas are benign, hormone-responding tumours of, respectively, smooth
      muscles and fibroblasts and their aetiology induces a significant interest. In
      myomas the presence of aromatase was detected and, in addition, oestrogen was
      found to be synthesized in myoma cells. The studies were performed on myoma
      patients of generative age and those in peri-menopausal age. Expression of TRAF2
      and TRAF6 proteins was examined using immunohistochemistry and Western blot
      approach in small and large uterine myomas isolated from women of various age. In
      addition, the evaluation was conducted at the periphery of every myoma. We
      indicated that the level of both tested proteins in myomas is higher than in
      control. TRAF2 level in myometrium was lower than in myomas but higher than in
      control. In the case of TRAF6 those changes were ambiguous. Age didn't have
      influence the level of expression in both tested TRAF in studied structures.

PMID- 21071348
TI  - Expression of MUC1 mucin in human umbilical vein endothelial cells (HUVEC).
AB  - Mucin 1 (MUC1) is a membrane-bound glycoprotein that is expressed by various
      epithelial cell types. MUC1 functions include modulation of cell adhesion, signal
      transduction, lubrication and hydration of epithelial surfaces, and their
      protection from infection. In this study we demonstrated that MUC1 is expressed
      in human umbilical vein endothelial cells (HUVECs) and could be released/shed
      from cellular membrane. MUC1 presence in these cells was verified using three
      methods: Western blotting, flow cytometry and metabolic labeling. We also showed
      that mucin expression is stimulated by proinflammatory cytokines: about a 2-fold
      increase was observed after TNF-alpha treatment and lower after IFN-gamma alone
      and in combination with TNF-alpha treatment. It can be assumed that the presence
      of MUC1 in endothelial cells may have an important role in the interactions with
      different cell types in physiological and pathological processes.

PMID- 21071349
TI  - Fas/FasL expression in colorectal cancer. An immunohistochemical study.
AB  - The objective of the current study was to assess the expression of Fas ligand
      (FasL) and Fas receptor (FasR) as the proteins of the post-mitochondrial
      apoptotic pathway in colorectal carcinoma and to investigate correlations between
      their expression and chosen clinico-pathological parameters. The protein
      expression was analyzed in 50 colorectal carcinoma patients, using the
      immunohistochemical method. Reaction for FasR was weak in 75.5% and strong in
      24.5% of the study patients, as compared to normal glandular epithelium where
      FasR expression was strong in 100% of cases. On the other hand, FasL expression
      was found to be weak in 30% and strong in 70% of colorectal cancer patients, as
      compared to its lack in 100% of normal colorectal epithelium. Statistical
      analysis showed strong expression of FasL was found to correlate statistically
      significantly with vascular invasion (p = 0.005). No correlations of FasL and
      FasR expression in the main mass of tumor was found between other clinic
      pathological parameters. Fas ligand and Fas receptor appeared to be of little
      usefulness as prognostic factors for different groups of colorectal carcinoma
      patients. However, these proteins could become good therapeutic targets for
      colorectal carcinoma since their expression differs distinctly between normal
      intestinal epithelium and cancer cells, and known is the mechanism by which
      cancer cells escape death via apoptosis-inducing Fas/FasL pathway disorders.

PMID- 21071350
TI  - Histopathological evaluation of recurrent goiter.
AB  - The recurrent goiter is the regrowth of thyroid tissue after thyroidectomy. An
      inadequate surgical removal of the thyroid gland, lack of substitution therapy
      and pathological stimulation of the thyroid growth can all promote the
      recurrence. The aim of this study was to find the connection between the
      histopathological findings during the first and second operation and the
      recurrence of goiter. The study group consisted of 29 women and 1 man. The mean
      time to recurrence was 15 years. The most frequent histopathological finding
      during the first and second operation was struma nodosa. According to our
      observations different histopathological findings were found in 63.4% cases after
      primary and secondary thyroidectomy. Some genetic investigations showed that
      nodules in recurrent goiters did not derive from nodules left during the first
      operation but from a group of cells which had high growth potential. Thus, not
      only the operation technique and substitution after operation are key factors of
      successful therapy of goiter, but also other factors which stimulate the re
      growth of thyroid tissue.

PMID- 21071351
TI  - The effects of docosahexaenoic acid on glial derived neurotrophic factor and
      neurturin in bilateral rat model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is
      the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the
      brain and is required for normal cellular function. Glial cell line derived
      neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors
      for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF
      and NTN by investigating their immunostaining levels after administration of DHA
      in a model of PD. For this reason we hypothesized that DHA administration of PD
      might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic
      neurodegeneration was used to create the experimental Parkinsonism model. Rats
      were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP
      induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly
      decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this,
      DHA administration protected dopaminergic neurons as shown by tyrosine
      hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN
      immunoreactions in dopaminergic neurons were higher than that of the MPTP group.
      In conclusion, the characterization of GDNF and NTN will certainly help elucidate
      the mechanism of DHA action, and lead to better strategies for the use of DHA to
      treat neurodegenerative diseases.

PMID- 21071352
TI  - Morphological and immunohistochemical comparison of three rat prostate lobes
      (lateral, dorsal and ventral) in experimental hyperprolactinemia.
AB  - The prolactin plays an important role in the regulation of growth and
      differentiation of prostate gland besides androgens. The goal of this study was
      to reveal the influence of elevated prolactin concentration on epithelial cells
      of prostate. We compared the morphology of epithelial cells of prostate dorsal,
      lateral and ventral lobes and expression of androgen receptors in these cells in
      rats with hyperprolactinemia and in control rats. We used sexually mature male
      Wistar rats. The experimental rats received metoclopramide; the control group
      received saline in the same way. The prostate dorsal, lateral and ventral lobes
      were collected routinely for light and electron microscopy. The intensity of
      immunohistochemical reaction of androgen receptor in epithelial cells of dorsal,
      lateral and ventral lobes was evaluated by measure of optical density with
      computer image analysis. The light and electron (transmission and scanning)
      microscopes were used for morphological observations. RESULTS: In experimental
      rats twofold increase in prolactin and twofold decrease in testosterone found. In
      experimental group the expression of androgen receptor was lower in columnar
      epithelial cells of dorsal and ventral lobes but higher in lateral one. We
      observed morphological abnormalities in columnar epithelial cells of lateral and
      dorsal lobes. The columnar epithelial cells of ventral lobes didn't show any
      morphological changes in hyperprolactinemia.

PMID- 21071353
TI  - MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in
      experimental rats.
AB  - Recent studies have suggested that inflammation actively participates in
      ascending aortic aneurysm formation. The aim of the present study was to evaluate
      the expression changes of adhesion molecules and MMPs in an experimental model of
      ascending aortic aneurysm induced by ascending aorta banding in Wistar rats.
      Twelve rats developed aortic dilation after ascending aorta banding treatment,
      while nine normal animals underwent surgery without banding were used as
      controls. Light microscope and scanning electron microscope showed that the wall
      of the ascending aorta became disorganized as well as infiltration by
      inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a
      significant increase in the immunostaining of MCP-1 was observed in the
      aneurysmal wall as compared to the normal aortic wall. Under similar experimental
      conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was
      markedly increased in the aneurysmal wall. In addition, gelatin zymographic
      analysis showed that the expression and activities of MMP-2 and MMP-9 were
      remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as
      compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1
      are involved in the pathogenesis of ascending aortic aneurysm and an increase in
      the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of
      ascending aortic aneurysm.

PMID- 21071354
TI  - The tunica mucosa of the oviduct in case of ovarian cysts presence in sows.
AB  - The unfavorable morphological changes in the oviductal mucosa may lead to
      infertility in females and be one of the reasons for slaughtering of farm
      animals. The aim of study was to investigate the morphological changes in the
      epithelium of oviductal mucosa of sows with ovarian cysts. The oviducts of 18
      sows were obtained after slaughter. Sows were divided into three groups: 1st
      group - 6 sows with polycystic ovaries, 2nd group - 6 sows with single cysts, 3rd
      group - 6 sows without ovarian cysts. The epithelium was examined by light
      microscopy, SEM and TEM. Ciliated and secretory cells were count on 150 MUm
      segments in apical and basal zone of folds both in ampulla and isthmus. We
      analyzed the number of cells in 5 folds in both these oviductal parts in dexter
      and sinister oviduct. We have noted unfavorable changes in oviductal mucosa
      consisting in increase of the secretory cells with simultaneous decrease of
      ciliated cells. The correlations between the general occurrence of ovarian cysts
      and the morphological state of epithelium of oviductal tunica mucosa were
      determined. The changes in proportion of cells occurred both in ampulla and
      isthmus. The excessive secretion covering epithelium promotes agglutinations and
      adhesions of the tubal folds and occlusion of the oviduct. These alterations may
      create problems in the migration of gametes and prevent the movements of the
      zygote towards the uterus and cause some disturbances in conceptus development in
      its early stages. Results suggest that COD is connected with unfavorable
      morphological and functional changes within epithelium of the oviductal tunica
      mucosa.

PMID- 21071355
TI  - The activity of selected glycosidases in salivary gland tumors.
AB  - The monitoring of the patients after salivary gland tumors surgery is an
      important clinical issue. Still imperfect diagnostic procedures also remain a
      challenge for searching new sensitive and specific biomarkers of neoplastic
      processes in salivary glands. The aim of the presented study was an the
      assessment of the activity of HEX, with its isoforms HEX-A and HEX-B, GLU, GAL,
      MAN and FUC in salivary gland tumor tissues in comparison to a healthy salivary
      gland tissues taken during autopsy. A group of 42 patients with benign and
      malignant salivary gland tumors, aged 25-65 were examined. Fragments of salivary
      gland tumor tissue, fragments of healthy tissue removed during autopsy, blood
      serum and saliva were collected from patients with salivary gland tumors and
      healthy volunteers. In salivary gland tumor tissue the activity of HEX, HEX-A,
      HEX-B, GAL, FUC was considerably higher than in comparison to healthy salivary
      gland tissue and ascending trend of activity of GLU, MAN was also noticed. The
      activity of all lysosomal exoglycosidases in blood serum in patients with
      salivary gland tumors was considerably higher in comparison to healthy volunteers
      blood serum. The considerably higher activity of HEX, HEX-A, GLU, GAL, MAN, FUC
      and descending trend of activity of HEX-B were noticed in saliva of patients with
      salivary gland tumors in comparison to healthy volunteers. The assessment of HEX
      in blood serum and saliva of patients with salivary gland tumor can be possibly
      used in diagnostics and monitoring of salivary glands tumors.

PMID- 21071356
TI  - Somatostatin, substance P and calcitonin gene-related peptide-positive intramural
      nerve structures of the human large intestine affected by carcinoma.
AB  - The aim of this study was to investigate the arrangement and chemical coding of
      enteric nerve structures in the human large intestine affected by cancer. Tissue
      samples comprising all layers of the intestinal wall were collected during
      surgery form both morphologically unchanged and pathologically altered segments
      of the intestine (n=15), and fixed by immersion in buffered paraformaldehyde
      solution. The cryostat sections were processed for double-labelling
      immunofluorescence to study the distribution of the intramural nerve structures
      (visualized with antibodies against protein gene-product 9.5) and their chemical
      coding using antibodies against somatostatin (SOM), substance P (SP) and
      calcitonin gene-related peptide (CGRP). The microscopic observations revealed
      distinct morphological differences in the enteric nerve system structure between
      the region adjacent to the cancer invaded area and the intact part of the
      intestine. In general, infiltration of the cancer tissue resulted in the gradual
      (depending on the grade of invasion) first decomposition and reduction to final
      partial or complete destruction and absence of the neuronal elements. A
      comparative analysis of immunohistochemically labeled sections (from the
      unchanged and pathologically altered areas) revealed a statistically significant
      decrease in the number of CGRP-positive neurons and nerve fibres in both
      submucous and myenteric plexuses in the transitional zone between morphologically
      unchanged and cancer-invaded areas. In this zone, a decrease was also observed in
      the density of SP-positive nerve fibres in all intramural plexuses. Conversely,
      the investigations demonstrated statistically insignificant differences in number
      of SP- and SOM-positive neurons and a similar density of SOM-positive nerve
      fibres in the plexuses of the intact and pathologically changed areas. The
      differentiation between the potential adaptive changes in ENS or destruction of
      its elements by cancer invasion should be a subject of further investigations.

PMID- 21071358
TI  - Editorial--a world in progress...
AB  - THIS YEAR WAS THE CENTENNIAL OF FLORENCE Nightingale's death and in
      commemoration, was designated as the International Year of the Nurse (IYNurse) by
      The Honor Society of Nursing, Sigma Theta Tau in the U.S., The Nightingale
      Initiative for Global Health in Canada, and the Florence Nightingale Museum in
      England. 2010 IYNurse is "a collaborative, grassroots global initiative honoring
      nurses' voices, values, and wisdom-to act as catalysts for achieving a healthy
      world." In this "celebration of commitment," we honor Florence Nightingale as the
      founder of modern nursing and for the legacy she left us and we recognize the
      contributions of nurses today, all over the world. At the 2010 IYNurse website,
      you can read stories contributed by nurses that illustrate progress made in each
      of the eight UN Millennium Development Goals. Another section of the website
      contains tributes to nurses and to the nursing experience. A video of the
      Commemorative Global Service Celebrating Nursing that took place this past April
      at the Washington National Cathedral is also available for viewing. I hope you
      will visit this website and possibly make a contribution to nursing's story.

PMID- 21071359
TI  - Neonatal cardiac tamponade and pleural effusion resolved with chest tube
      placement.
AB  - Pericardial effusion and cardiac tamponade secondary to umbilical venous
      catheterization are rare complications but potentially fatal. This article
      reports a case of cardiac tamponade and right pleural effusion secondary to
      transudation of hyperosmolar fluid from an appropriately placed umbilical venous
      catheter. The infant survived as a result of early diagnosis by echocardiography
      and urgent chest tube placement that drained both pleural and pericardial
      effusions. Cardiac tamponade should be highly suspected in any neonate with a
      central venous catheter who develops sudden, unexplained clinical deterioration
      in cardiopulmonary status even when the line is properly placed, and urgent
      echocardiography or pericardiocentesis should be considered early in management
      of such patients. Umbilical venous catheterization should be considered only for
      a select group of sick neonates due to risks involved with these lines. When an
      umbilical venous catheter is placed, special precautions should be taken and
      maintenance guidelines followed.

PMID- 21071360
TI  - An ounce of prevention: decreasing painful interventions in the NICU.
AB  - Despite a proliferation of literature relative to pain physiology, assessment,
      and treatment, pain management in NICUs remains inconsistent--most often focused
      on assessment and treatment rather than prevention. The acceptance of pain as an
      inevitable part of NICU hospitalization is part of the culture in many NICUs.
      This article is intended to encourage discussion of pain prevention in the NICU,
      with a goal of creating a new "minimal-pain" NICU culture. The focus of NICU pain
      management programs should be on decreasing the number of painful events the NICU
      patient experiences. Areas for consideration include assessing the performance of
      procedures by novice versus experienced NICU personnel, reevaluating the role of
      pediatric residents in the treatment of NICU patients, evaluating the use of
      umbilical lines and peripherally inserted central catheters to reduce the
      frequency of peripheral punctures, and evaluating the admission process for ways
      to reduce neonatal pain and stress. This article discusses the physiology of pain
      in the neonate, identifies adverse outcomes related to repeated pain, and
      proposes practice changes that can prevent unnecessary pain in neonatal care.

PMID- 21071361
TI  - Sensorimotor interventions improve growth and motor function in preterm infants.
AB  - PURPOSE: To assess the effect of an oral (O+O), a tactile/kinesthetic (T/K+T/K),
      and a combined (O+T/K) intervention on preterm infants' weight gain and motor
      function and to determine whether the combined O+T/K intervention has an
      additive/synergistic effect on outcomes. DESIGN/SAMPLE: Seventy-five preterm
      infants were randomized into an O+O intervention consisting of oral stimulation,
      a T/K+T/K intervention involving whole body stimulation, an O+T/K intervention,
      and a control group. Interventions were administered for 15 minutes, twice a day,
      for ten days. OUTCOMES: Weight gain, motor function. RESULTS: The O+O and T/K+T/K
      groups had greater weight gain during the intervention period than did controls
      (p <=.025). The T/K+T/K and O+T/K groups had better motor function than did
      controls (p <=.017). CONCLUSION: Single and combined interventions improved
      growth and motor function. The combined intervention, because of the shorter
      duration of each modality, did not lead to additive/synergistic effects,
      suggesting that the duration of the sensorimotor input is as important as its
      target in achieving defined outcomes.

PMID- 21071362
TI  - Nonimmune hydrops fetalis part II: does etiology influence mortality?
AB  - Hydrops fetalis is a condition in which there is an excess of total body fluid,
      primarily within the fetal interstitial spaces. Etymologically, hydrops fetalis
      is a Latin term meaning "edema of the fetus." In addition to generalized edema,
      the fetus has at least one of the following: ascites, pericardial effusion,
      pleural effusion(s), and an abnormally thick (>6 cm) placenta. Hydrops is
      classified as nonimmune hydrops fetalis (NIHF) when it occurs without evidence of
      isoimmunization.

PMID- 21071364
TI  - Fetal fibronectin: what does it mean?

PMID- 21071366
TI  - Is your nursery full of MDROs?
AB  - Multidrug-resistant organisms (MDROs) or multiresistant organisms are a
      significant and growing concern to all of us. Late-onset methicillin-resistant
      Staphylococcus aureus (MRSA) infections in the NICU are reported to have
      increased by 308 percent from 1995 to 2004.1 The Centers for Disease Control and
      Prevention (CDC) Healthcare Infection Control Practices Advisory Committee
      considers the prevention and control of MDROs a national priority, one that
      requires administrative and scientific leadership. This campaign will take
      commitment of financial resources, as well as of human resources devoted to
      practice improvement, expert consultation, laboratory support, monitoring of
      adherence to the practices that help with the problem, and data analysis.2
      Unfortunately, this trend holds in developing countries as well. MDROs are a
      clinical challenge the world over.

PMID- 21071367
TI  - Podcasts, webcasts, sims, and more: new and innovative ways for nurses to learn.
AB  - ADVANCES IN TECHNOLOGY HAVE expanded the educational tools and learning options
      available to today's nurses. Among these technologically enhanced tools and
      strategies are online learning, podcasts, vodcasts, webcasts, webinars,
      discussion forums, mobile learning, realistic simulations, and others. What
      exactly are these options? Which ones are the most effective? This is the first
      topic we will address in a new column on educational strategies in the NICU, a
      column designed to familiarize NICU nurse educators, clinical nurse specialists,
      managers, and preceptors with innovative and evidenced-based teaching strategies
      that promote optimal learning among NICU nurses. The purpose of this first column
      is to provide an introduction to innovative teaching tools and strategies-some
      technologically enhanced, some not-including such nontechnological interactive
      educational activities as problem-based learning, games, and concept maps. Future
      columns will discuss many of these strategies in more detail.

PMID- 21071368
TI  - Thomas Hill: a courageous premie and his loving family.

PMID- 21071369
TI  - Pancreatic endocrine tumors: radiologic-clinicopathologic correlation.
AB  - Pancreatic endocrine tumors (PETs) are primarily well-differentiated tumors
      composed of cells that resemble normal islet cells but that arise from pancreatic
      ductal cells. They are classified as functioning or nonfunctioning according to
      their associated clinical symptoms; insulinoma, gastrinoma, and glucagonoma are
      the most common functioning PETs. They also are classified according to their
      biologic behavior, although all PETs have malignant potential. Most are sporadic,
      but some are associated with familial syndromes such as multiple endocrine
      neoplasia type 1, von Hippel-Lindau syndrome, and neurofibromatosis type 1. At
      imaging, PETs typically appear as well-defined hypervascular masses, a finding
      indicative of their rich capillary network. Cystic change, calcification, and
      necrosis are common in large tumors, which are associated with a poorer prognosis
      and a higher prevalence of local and vascular invasion and metastases than are
      smaller tumors. Even when metastases are present, many well-differentiated PETs
      have an indolent course. Poorly differentiated PETs are rare and have an
      infiltrative appearance; patients with such tumors have a poor prognosis.
      Knowledge of the characteristic clinical, pathologic, and radiologic features of
      PETs is important in the evaluation and management of patients with a suspected
      clinical syndrome or a pancreatic mass.

PMID- 21071370
TI  - Comprehensive update on select immune-mediated gastroenterocolitis syndromes:
      implications for diagnosis and management.
AB  - There is a heterogeneous group of noninfectious gastroenterocolitis syndromes
      that are characterized by immune dysregulation. Recent advances in pathologic
      analysis have allowed for better characterization of many of these disorders.
      Some entities demonstrate characteristic disease distribution, epidemiologic
      features, natural history, and response to specific therapy. For instance, celiac
      disease occurs in genetically susceptible individuals who are sensitive to
      gluten, eosinophilic esophagitis is an immune response to ingested allergens, and
      microscopic colitis predominantly occurs in older patients with chronic diarrhea
      and is induced or exacerbated by drugs. Eosinophilic gastroenteritis has a
      variety of clinical and imaging manifestations. Crohn disease and ulcerative
      colitis are multifactorial immune-mediated chronic inflammatory disorders and
      have become increasingly prevalent in recent years. Multidetector computed
      tomography and magnetic resonance imaging provide valuable information that may
      be used to diagnose these conditions, guide treatment, and assess changes after
      treatment, and the role of imaging in evaluating response to therapy continues to
      evolve and expand.

PMID- 21071371
TI  - Complications of congenital and developmental abnormalities of the
      gastrointestinal tract in adolescents and adults: evaluation with multimodality
      imaging.
AB  - There is a wide variety of congenital anomalies that may affect the
      gastrointestinal tract. Most symptomatic congenital anomalies are found in
      newborns and infants. Such anomalies are relatively rare in adolescents and
      adults, and they may be difficult to identify because clinical symptoms often are
      nonspecific and insidious, causing them to be mistaken for other common abdominal
      conditions. Multimodality imaging is useful in evaluating congenital anomalies of
      the gastrointestinal tract in adults. The imaging features at radiography,
      fluoroscopy, ultrasonography, computed tomography, and magnetic resonance imaging
      may help identify congenital gastrointestinal anomalies such as congenital
      esophageal stenosis, gastric volvulus, duodenal web, annular pancreas,
      heterotopic pancreas, cecal volvulus, anomalies of the omphalomesenteric duct,
      Hirschsprung disease, and gastrointestinal duplication cyst. Familiarity with the
      imaging features of the various congenital anomalies of the gastrointestinal
      tract and their complications is important to establish the correct diagnosis and
      determine appropriate treatment, which is critical to avoid life-threatening
      complications.

PMID- 21071372
TI  - Adult renal cystic disease: a genetic, biological, and developmental primer.
AB  - Renal cystic diseases in adults are a heterogeneous group of disorders
      characterized by the presence of multiple cysts in the kidneys. These diseases
      may be categorized as hereditary, acquired, or developmental on the basis of
      their pathogenesis. Hereditary conditions include autosomal dominant polycystic
      kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and
      tuberous sclerosis. Acquired conditions include cystic kidney disease, which
      develops in patients with end-stage renal disease. Developmental cystic diseases
      of the adult kidney include localized renal cystic disease, multicystic
      dysplastic kidney, and medullary sponge kidney. In recent years, many molecular
      and cellular mechanisms involved in the pathogenesis of renal cystic diseases
      have been identified. Hereditary renal cystic diseases are characterized by
      genetic mutations that lead to defects in the structure and function of the
      primary cilia of renal tubular epithelial cells, abnormal proliferation of
      tubular epithelium, and increased fluid secretion, all of which ultimately result
      in the development of renal cysts. A better understanding of these
      pathophysiologic mechanisms is now providing the basis for the development of
      more targeted therapeutic drugs for some of these disorders. Cross-sectional
      imaging provides useful information for diagnosis, surveillance, prognostication,
      and evaluation of treatment response in renal cystic diseases.

PMID- 21071373
TI  - Mesenchymal neoplasms of the kidney in adults: imaging spectrum with radiologic
      pathologic correlation.
AB  - Mesenchymal neoplasms of the kidney in adults cover a wide spectrum with
      characteristic ontogeny and histologic findings and variable biologic profiles
      and imaging findings. Benign mesenchymal renal tumors include angiomyolipoma,
      leiomyoma, hemangioma, lymphangioma, juxtaglomerular cell tumor, renomedullary
      interstitial cell tumor (medullary fibroma), lipoma, solitary fibrous tumor, and
      schwannoma. Malignant renal tumors of mesenchymal origin include leiomyosarcoma,
      rhabdomyosarcoma, angiosarcoma, osteosarcoma, synovial sarcoma, fibrosarcoma,
      malignant fibrous histiocytoma, and solitary fibrous tumor. Cross-sectional
      imaging findings for mesenchymal renal tumors in adults are varied. Although
      angiomyolipomas and lipomas show macroscopic fat, lymphangiomas are cystic in
      appearance. Renal hemangioma may show phleboliths and a characteristic
      enhancement pattern. Leiomyoma typically arises from the capsule and causes
      buckling of the renal cortex. Although osteosarcoma may demonstrate
      characteristic dense ossification, most renal sarcomas demonstrate imaging
      features that are indistinguishable from the more common renal cell carcinoma.
      Although some renal mesenchymal tumors have typical imaging findings, biopsy is
      warranted to establish a definitive diagnosis. Awareness of the various
      mesenchymal renal tumors and familiarity with their imaging findings permit
      optimal patient management.

PMID- 21071374
TI  - Mixed epithelial and stromal tumor of the kidney: radiologic-pathologic
      correlation.
AB  - Mixed epithelial and stromal tumor (MEST) of the kidney is a rare, typically
      benign lesion that occurs predominantly in perimenopausal women. At computed
      tomography (CT), it typically manifests as a multiloculated cystic renal mass
      with a variable proportion of solid and cystic components and containing internal
      septa that demonstrate heterogeneous and delayed contrast material enhancement.
      MEST may mimic a variety of benign and malignant renal lesions, such as adult
      cystic nephroma, complex renal cyst, and cystic renal cell carcinoma. The
      preoperative diagnosis of MEST can be problematic, and most cases are treated
      surgically. However, CT with two-dimensional multiplanar reformation and three
      dimensional volume rendering helps define the diagnostic features of MEST and can
      assist in surgical planning.

PMID- 21071375
TI  - Urothelial cancer of the renal pelvicaliceal system: unusual imaging
      manifestations.
AB  - Unusual imaging features of urothelial cancer of the renal pelvicaliceal system
      can be challenging for any radiologist. These manifestations include noncalcified
      and calcified focal infiltrative parenchymal masses, incidentally detected tumors
      in a hydronephrotic kidney due to ureteropelvic junction obstruction, transpelvic
      infiltrating solid masses extending through the retroperitoneum, and tumors
      primarily invading the perirenal fat. Less common manifestations include massive
      papillary frond-like projections within a large hydronephrotic sac, large
      multiloculated cystic masses with thick and irregular septa, tumors invading the
      renal vein, and paraaortic lymph node metastases as the only sign of an
      undetectable primary tumor of the renal collecting system. Radiologists should be
      aware that an eccentric, focal, infiltrative pelvicaliceal carcinoma that causes
      distortion of the renal contour may simulate renal cell carcinoma; when
      calcified, such a pelvicaliceal carcinoma may simulate chronic inflammatory renal
      disease. The radiologist should also be aware of the importance of a meticulous
      sonographic evaluation of a hydronephrotic kidney, particularly in older
      patients, to avoid missing a urothelial cancer. When a nonfunctioning and
      enlarged kidney is present, radiologists should always consider infiltrative
      hydronephrotic urothelial carcinoma as a diagnostic possibility. Familiarity with
      unusual imaging features of urothelial cancer of the renal pelvicaliceal system
      may facilitate making the correct diagnosis, thus enabling adequate therapeutic
      management.

PMID- 21071376
TI  - Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT
      with pathologic correlation.
AB  - Sarcoidosis is a multisystem disorder that is characterized by noncaseous
      epithelioid cell granulomas, which may affect almost any organ. Thoracic
      involvement is common and accounts for most of the morbidity and mortality
      associated with the disease. Thoracic radiologic abnormalities are seen at some
      stage in approximately 90% of patients with sarcoidosis, and an estimated 20%
      develop chronic lung disease leading to pulmonary fibrosis. Although chest
      radiography is often the first diagnostic imaging study in patients with
      pulmonary involvement, computed tomography (CT) is more sensitive for the
      detection of adenopathy and subtle parenchymal disease. Pulmonary sarcoidosis may
      manifest with various radiologic patterns: Bilateral hilar lymph node enlargement
      is the most common finding, followed by interstitial lung disease. At high
      resolution CT, the most typical findings of pulmonary involvement are
      micronodules with a perilymphatic distribution, fibrotic changes, and bilateral
      perihilar opacities. Atypical manifestations, such as masslike or alveolar
      opacities, honeycomb-like cysts, miliary opacities, mosaic attenuation,
      tracheobronchial involvement, and pleural disease, and complications such as
      aspergillomas, also may be seen. To achieve a timely diagnosis and help reduce
      associated morbidity and mortality, it is essential to recognize both the typical
      and the atypical radiologic manifestations of the disease, take note of features
      that may be suggestive of diseases other than sarcoidosis, and correlate imaging
      features with pathologic findings to help narrow the differential diagnosis.

PMID- 21071377
TI  - Myocardial fat at cardiac imaging: how can we differentiate pathologic from
      physiologic fatty infiltration?
AB  - Myocardial fat is often seen at cardiac computed tomography (CT) and magnetic
      resonance (MR) imaging of healthy adults and patients with myocardial diseases.
      Physiologic myocardial fat develops with aging and is commonly seen at CT in the
      anterolateral right ventricular (RV) free wall and RV outflow tract with normal
      or thickened RV myocardium and a normal-sized RV in elderly patients. Pathologic
      conditions with myocardial fat include healed myocardial infarction (MI);
      arrhythmogenic RV cardiomyopathy or dysplasia (ARVC); and others, such as cardiac
      lipoma, lipomatous hypertrophy of the interatrial septum, tuberous sclerosis
      complex, dilated cardiomyopathy, and cardiomyopathy with muscular dystrophy. In
      patients with healed MI, CT and MR imaging show fat in left ventricular
      myocardium that is of normal thickness or thin and follows the distribution of
      the coronary artery; CT often depicts fat in mostly subendocardial regions. In
      patients with ARVC, characteristic CT and MR imaging findings include a thin RV
      outflow tract and free wall caused by subepicardial fatty infiltration; fat in
      the RV moderator band, trabeculae, and ventricular septum; and RV enlargement and
      wall motion abnormality. Recognition of patient age, characteristic locations of
      myocardial fat, myocardial thickness, and ventricular size helps in
      differentiating physiologic and pathologic myocardial fat at cardiac imaging;
      findings of wall motion abnormality and late gadolinium enhancement at MR imaging
      help narrow the diagnosis.

PMID- 21071378
TI  - CT and MR imaging of the mitral valve: radiologic-pathologic correlation.
AB  - Computed tomography (CT) and magnetic resonance (MR) imaging are increasingly
      important adjuncts to echocardiography for the evaluation of mitral valve
      disease. The mitral valve may be involved in various acquired or congenital
      conditions with resultant regurgitation or stenosis, and many of these conditions
      can be identified with CT or MR imaging. In addition, CT is useful for detecting
      and monitoring postoperative complications after mitral valve repair or
      replacement. As the use of CT and MR imaging increases, awareness of the CT and
      MR imaging appearances of the normal mitral valve and the various disease
      processes that affect it may foster recognition of unsuspected mitral disease in
      patients undergoing imaging for other purposes. Supplemental material available
      at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.306105518/-/DC1.

PMID- 21071379
TI  - Subungual tumors: clinicopathologic correlation with US and MR imaging findings.
AB  - Various types of tumors can affect the subungual space, including benign solid
      tumors (glomus tumor, subungual exostosis, soft-tissue chondroma,
      keratoacanthoma, hemangioma, lobular capillary hemangioma), benign cystic lesions
      (epidermal and mucoid cysts), and malignant tumors (squamous cell carcinoma,
      malignant melanoma). Imaging plays an important role in the detection and
      differentiation of subungual tumors because of their small size, nonspecific
      clinical manifestations, and functional significance. Ultrasonography (US)-in
      particular, high-resolution US with color Doppler studies-provides useful
      information regarding tumor size, location, shape, and internal characteristics
      (cystic, solid, or mixed), but it is limited in the further characterization of
      tissue. Magnetic resonance (MR) imaging has an important role in categorizing
      tumors according to their anatomic location, pathologic origin, and signal
      characteristics. There is some overlap between the US and MR imaging features of
      subungual tumors; however, certain features can allow accurate diagnosis and
      expedite management when correlated with clinical and pathologic findings.

PMID- 21071380
TI  - Anatomy, biomechanics, imaging, and management of ligamentum teres injuries.
AB  - The ligamentum teres has traditionally been viewed as an embryonic remnant with
      no role in the biomechanics or vascularity of adult hips. However, the ligamentum
      teres is a strong intraarticular ligament that is anatomically and biochemically
      similar to the anterior cruciate ligament of the knee. It is composed of two
      bands that originate from the acetabular transverse ligament and the pubic and
      ischial margins of the acetabular notch. Among other functions, the ligamentum
      teres is an important stabilizer of the hip, particularly in adduction, flexion,
      and external rotation. Abnormalities of the ligamentum teres account for 4%-15%
      of sports-related injuries and should be considered in the differential diagnosis
      of patients with hip pain. Lesions of the ligamentum teres include partial or
      complete traumatic tears, degenerative tears, avulsion fractures of the ligament
      at its insertion into the fovea capitis femoris, and a congenital absence of the
      ligament. Magnetic resonance arthrography and computed tomographic arthrography
      are the preferred modalities for precise preoperative diagnosis of ligamentum
      teres injuries and may be used to rule out other associated intraarticular
      injuries. Treatment of these lesions is still evolving; at present, treatment of
      most injuries is limited to arthroscopic debridement.

PMID- 21071381
TI  - Imaging characteristics of primary osteosarcoma: nonconventional subtypes.
AB  - Osteosarcoma (OS) is a common primary malignant tumor of bone that produces
      osteoid matrix. According to the World Health Organization, OS of bone is
      classified into eight subtypes with distinct biologic behaviors and clinical
      outcomes: conventional, telangiectatic, small cell, low-grade central, secondary,
      parosteal, periosteal, and high-grade surface. Imaging plays a crucial role in
      the diagnosis of each subtype of OS and ultimately in patients' survival because
      the diagnosis is based on a combination of histopathologic and imaging features.
      Conventional OS is the most common subtype of OS and is readily identified at
      radiography as an intramedullary mass with immature cloudlike bone formation in
      the metaphyses of long bones. The imaging features of less common subtypes of
      primary OS are variable and frequently overlap with those of multiple benign and
      malignant entities, creating substantial diagnostic challenges. For accurate
      diagnosis, it is important to be aware of radiographic and cross-sectional
      imaging features that allow differentiation of each nonconventional subtype of OS
      from its mimics.

PMID- 21071382
TI  - Ductal carcinoma in situ of the breast: MR imaging findings with histopathologic
      correlation.
AB  - Ductal carcinoma in situ (DCIS) is a noninvasive malignancy that is commonly
      encountered at routine breast imaging. It may be a primary tumor or may be seen
      in association with other focal higher-grade tumors. Early detection is important
      because of the large proportion of DCIS that can progress to invasive carcinoma.
      The extent of DCIS involvement is frequently underestimated at mammography, which
      can reliably help detect only calcified DCIS; consequently, magnetic resonance
      (MR) imaging evaluation can alter the course of treatment. Seven biopsy-proved
      cases of DCIS were evaluated with T2-weighted MR imaging sequences, as well as T1
      weighted sequences performed both before and after contrast material
      administration. The signal intensity and enhancement patterns of the tumors were
      analyzed, and the findings were correlated with the relevant underlying
      histopathologic features. Common enhancement patterns of DCIS include clumped
      linear-ductal enhancement, clumped focal enhancement, and masslike enhancement.
      The most common enhancement distribution pattern is segmental, followed by focal,
      diffuse, linear-ductal, and regional patterns. At T2-weighted MR imaging, DCIS is
      typically isointense relative to breast parenchyma; less commonly, it is
      hypointense or hyperintense. The use of MR imaging in the evaluation of DCIS is
      controversial, and many questions remain with regard to treatment and management.
      However, breast MR imaging can be extremely useful in the preoperative diagnosis
      and evaluation of DCIS when used in conjunction with other imaging modalities.

PMID- 21071383
TI  - Can MR Imaging contribute in characterizing well-circumscribed breast carcinomas?
AB  - Most well-circumscribed breast masses are benign lesions such as cysts,
      fibroadenomas, and intramammary lymph nodes. Nevertheless, 10%-20% of breast
      malignancies are well-circumscribed masses, and these malignancies include
      papillary, mucinous, medullary, and metaplastic carcinomas, as well as malignant
      phyllodes tumors. Therefore, it is important to differentiate these well
      circumscribed breast malignancies from benign breast lesions, but it is not easy
      to do so with conventional imaging modalities such as mammography and
      ultrasonography (US). As an emerging adjunctive imaging method, magnetic
      resonance (MR) imaging has substantial potential in characterizing well
      circumscribed breast carcinomas. Analysis of the lesion signal intensity on
      nonenhanced T2-weighted MR images, determination of the enhancement pattern, and
      kinetic curve assessment can greatly help differentiate malignant from benign
      well-circumscribed breast lesions. Therefore, breast MR imaging can play a
      substantial role in distinguishing between well-circumscribed benign and
      malignant breast lesions, especially in cases that are difficult to diagnose by
      using conventional imaging. In this article, the MR imaging findings of the
      subtypes of well-circumscribed malignant breast lesions-intracystic papillary
      carcinoma, invasive papillary carcinoma, mucinous carcinoma, medullary carcinoma,
      metaplastic carcinoma, and malignant phyllodes tumor-are described and correlated
      with the histopathologic, mammographic, and US findings.

PMID- 21071384
TI  - Neurocysticercosis: radiologic-pathologic correlation.
AB  - Neurocysticercosis is a neurologic parasitic disease caused by the encysted larva
      of the tapeworm Taenia solium and is the most important parasitic disease of the
      human central nervous system. It is the most common cause of acquired epilepsy in
      endemic settings and constitutes a public health challenge for most of the
      developing world. Nowadays, however, as a result of globalization,
      neurocysticercosis is being seen more frequently in developed countries as well.
      Neurocysticercosis is acquired through fecal-oral contamination, and the disease
      course is complex, with two intermediate hosts (ie, pigs and humans) and a
      definitive host (humans). Traditionally, it has been classified into active and
      nonactive forms according to disease location. Radiologists must be aware of its
      imaging appearance, which is quite variable, as is the differential diagnosis.
      Imaging findings depend on several factors, including the stage of the life cycle
      of T solium at presentation; the number and location (ie, subarachnoid,
      cisternal, or intraventricular) of parasites; and associated complications such
      as vascular involvement (ie, arteritis with or without infarction), inflammatory
      response (ie, edema, gliosis, or arachnoiditis), and, in ventricular forms,
      degree of obstruction. Thus, the diagnostic approach, management, and prognosis
      for neurocysticercosis differ widely depending on the type of infection.

PMID- 21071385
TI  - Congenital lung abnormalities: embryologic features, prenatal diagnosis, and
      postnatal radiologic-pathologic correlation.
AB  - Congenital lung abnormalities are being detected more frequently at routine high
      resolution prenatal ultrasonography. The most commonly encountered anomalies
      include lung agenesis-hypoplasia complex (pulmonary underdevelopment), congenital
      pulmonary airway malformations, congenital lobar overinflation, bronchial
      atresia, bronchogenic cysts, congenital high airway obstruction syndrome,
      scimitar syndrome, and bronchopulmonary sequestration. Recognizing the antenatal
      and postnatal imaging features of these abnormalities is necessary for optimal
      prenatal counseling and appropriate peri- and postnatal management. Supplemental
      material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.306105508/-/DC1.

PMID- 21071386
TI  - Cohort profile: The PharmAccess African (PASER-M) and the TREAT Asia (TASER-M)
      monitoring studies to evaluate resistance--HIV drug resistance in sub-Saharan
      Africa and the Asia-Pacific.

PMID- 21071388
TI  - Irregular RNA splicing curtails postsynaptic gephyrin in the cornu ammonis of
      patients with epilepsy.
AB  - Anomalous hippocampal inhibition is involved in temporal lobe epilepsy, and
      reduced gephyrin immunoreactivity in the temporal lobe epilepsy hippocampus has
      been reported recently. However, the mechanisms responsible for curtailing
      postsynaptic gephyrin scaffolds are poorly understood. Here, we have investigated
      gephyrin expression in the hippocampus of patients with intractable temporal lobe
      epilepsy. Immunohistochemical and western blot analyses revealed irregular
      gephyrin expression in the cornu ammonis of patients with temporal lobe epilepsy
      and four abnormally spliced gephyrins lacking several exons in their G-domains
      were isolated. Identified temporal lobe epilepsy gephyrins have oligomerization
      deficits and they curtail hippocampal postsynaptic gephyrin and GABA(A) receptor
      alpha2 while interacting with regularly spliced gephyrins. We found that cellular
      stress (alkalosis and hyperthermia) induces exon skipping in gephyrin messenger
      RNA, which is responsible for curtailed postsynaptic gephyrin and GABA(A)
      receptor alpha2 scaffolds. Accordingly, we did not obtain evidence for gephyrin
      gene mutations in patients with temporal lobe epilepsy. Cellular stress such as
      alkalosis, for example arising from seizure activity, could thus facilitate the
      development of temporal lobe epilepsy by reducing GABA(A) receptor alpha2
      mediated hippocampal synaptic transmission selectively in the cornu ammonis.

PMID- 21071389
TI  - Retrospective analysis of an oral combination of dexamethasone, uracil plus
      tegafur and cyclophosphamide for hormone-refractory prostate cancer.
AB  - OBJECTIVE: To evaluate the clinical utility of an oral combination of
      dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for
      patients with hormone-refractory prostate cancer. METHODS: Fifty-seven patients
      with hormone-refractory prostate cancer were treated with an oral administration
      of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and
      cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen
      patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and
      8 showed lymph node metastasis. Eight patients presented with only biochemical
      progression as evaluated by serum prostate-specific antigen levels. RESULTS:
      Thirty-six (63%) of 57 patients demonstrated a >=50% decline in serum prostate
      specific antigen levels. The median time to prostate-specific antigen progression
      was 7.2 months. In patients with a prostate-specific antigen decline of >=50%,
      the median time to progression was 13.3 months. With respect to pre-treatment
      markers, the duration of response to initial hormonal treatment was associated
      with the time to prostate-specific antigen progression. In 11 of 16 (69%)
      patients who complained of bone pain, the pain improved and became stable in 5 of
      those patients (31%). Most adverse events were mild and only three (5%) patients
      showed neutropenia of Grade 3 or higher. CONCLUSIONS: The combination of
      dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well
      tolerated regimen for hormone-refractory prostate cancer. To evaluate the
      survival benefits, further randomized studies are required.

PMID- 21071387
TI  - Multispectral brain morphometry in Tourette syndrome persisting into adulthood.
AB  - Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high
      prevalence of attention deficit hyperactivity and obsessive-compulsive disorder
      co-morbidities. Structural changes have been found in frontal cortex and striatum
      in children and adolescents. A limited number of morphometric studies in Tourette
      syndrome persisting into adulthood suggest ongoing structural alterations
      affecting frontostriatal circuits. Using cortical thickness estimation and voxel
      based analysis of T1- and diffusion-weighted structural magnetic resonance
      images, we examined 40 adults with Tourette syndrome in comparison with 40 age-
      and gender-matched healthy controls. Patients with Tourette syndrome showed
      relative grey matter volume reduction in orbitofrontal, anterior cingulate and
      ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into
      the limbic mesial temporal lobe. The grey matter changes were modulated
      additionally by the presence of co-morbidities and symptom severity. Prefrontal
      cortical thickness reduction correlated negatively with tic severity, while
      volume increase in primary somatosensory cortex depended on the intensity of
      premonitory sensations. Orbitofrontal cortex volume changes were further
      associated with abnormal water diffusivity within grey matter. White matter
      analysis revealed changes in fibre coherence in patients with Tourette syndrome
      within anterior parts of the corpus callosum. The severity of motor tics and
      premonitory urges had an impact on the integrity of tracts corresponding to
      cortico-cortical and cortico-subcortical connections. Our results provide
      empirical support for a patho-aetiological model of Tourette syndrome based on
      developmental abnormalities, with perturbation of compensatory systems marking
      persistence of symptoms into adulthood. We interpret the symptom severity related
      grey matter volume increase in distinct functional brain areas as evidence of
      ongoing structural plasticity. The convergence of evidence from volume and water
      diffusivity imaging strengthens the validity of our findings and attests to the
      value of a novel multimodal combination of volume and cortical thickness
      estimations that provides unique and complementary information by exploiting
      their differential sensitivity to structural change.

PMID- 21071390
TI  - Association between cannabis and cocaine use, traffic injuries and use of
      protective devices.
AB  - The effect of cannabis and cocaine use on non-fatal traffic injuries and use of
      motorcycle helmets or car seatbelts was assessed in a nationwide sample of 17,484
      car or motorcycle drivers surveyed in 2005 in Spain. Logistic regression was used
      to adjust for distance driven and potential confounders. Cocaine use >= 1
      day/week and cannabis use >4 days/week were associated with more traffic
      injuries. A positive dose-response relationship was found between frequency of
      cocaine use and lack of consistent use of protective devices. Interventions to
      avoid driving under the influence of drugs and to increase use of protective
      devices among drug users are needed.

PMID- 21071391
TI  - Gender differences in the association between education and the incidence of
      cardiovascular events in Northern Italy.
AB  - BACKGROUND: The educational differences in the incidence of major cardiovascular
      events are under-studied in Southern Europe and among women. METHODS: The study
      sample includes n = 5084 participants to 4 population-based Northern Italian
      cohorts, aged 35-74 at baseline and with no previous cardiovascular events. The
      follow-up to ascertain the first onset of coronary heart disease (CHD) or
      ischaemic stroke ended in 2002. At baseline, major cardiovascular risk factors
      were investigated adopting the standardized MONICA procedures. Two educational
      classes were obtained from years of schooling. Age- and risk factors-adjusted
      hazard ratios of first CHD or ischaemic stroke were estimated through sex
      specific separate Cox models (high education as reference). RESULTS: Median
      follow-up time was 12 years. Event rates were 6.38 (CHD) and 2.12 (ischaemic
      stroke) per 1000 person-years in men; and 1.59 and 0.94 in women. In men, low
      education was associated with higher mean Body Mass Index and prevalence of
      diabetes and cigarette smokers; but also with higher HDL cholesterol and a more
      favourable alcohol intake pattern. Less-educated women had higher mean systolic
      blood pressure, Body Mass Index and HDL cholesterol and were more likely to have
      diabetes. Men and women in the low educational class had a 2-fold increase in
      ischaemic stroke and CHD incidence, respectively, after controlling for major
      risk factors. Education was not associated with CHD incidence in men. Higher
      ischaemic stroke rates were observed among more educated women. CONCLUSION: In
      this northern Italian population, the association between education and
      cardiovascular risk seems to vary by gender.

PMID- 21071392
TI  - Pathway Commons, a web resource for biological pathway data.
AB  - Pathway Commons (http://www.pathwaycommons.org) is a collection of publicly
      available pathway data from multiple organisms. Pathway Commons provides a web
      based interface that enables biologists to browse and search a comprehensive
      collection of pathways from multiple sources represented in a common language, a
      download site that provides integrated bulk sets of pathway information in
      standard or convenient formats and a web service that software developers can use
      to conveniently query and access all data. Database providers can share their
      pathway data via a common repository. Pathways include biochemical reactions,
      complex assembly, transport and catalysis events and physical interactions
      involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims
      to collect and integrate all public pathway data available in standard formats.
      Pathway Commons currently contains data from nine databases with over 1400
      pathways and 687,000 interactions and will be continually expanded and updated.

PMID- 21071393
TI  - CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of
      large-scale omics data, bioinformatic analyses and curated annotation, with user
      rating and reviewing functionality.
AB  - The Ciona intestinalis protein database (CIPRO) is an integrated protein database
      for the tunicate species C. intestinalis. The database is unique in two respects:
      first, because of its phylogenetic position, Ciona is suitable model for
      understanding vertebrate evolution; and second, the database includes original
      large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a
      favorite of developmental biologists. Therefore, large amounts of data exist on
      its development and morphology, along with a recent genome sequence and gene
      expression data. The CIPRO database is aimed at collecting those published data
      as well as providing unique information from unpublished experimental data, such
      as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale
      analyses at various developmental stages, curated annotation data and various
      bioinformatic data, to facilitate research in diverse areas, including
      developmental, comparative and evolutionary biology. For medical and evolutionary
      research, homologs in humans and major model organisms are intentionally
      included. The current database is based on a recently developed KH model
      containing 36,034 unique sequences, but for higher usability it covers 89,683 all
      known and predicted proteins from all gene models for this species. Of these
      sequences, more than 10,000 proteins have been manually annotated. Furthermore,
      to establish a community-supported protein database, these annotations are open
      to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible
      at http://cipro.ibio.jp/2.5.

PMID- 21071394
TI  - Protein multiple sequence alignment by hybrid bio-inspired algorithms.
AB  - This article presents an immune inspired algorithm to tackle the Multiple
      Sequence Alignment (MSA) problem. MSA is one of the most important tasks in
      biological sequence analysis. Although this paper focuses on protein alignments,
      most of the discussion and methodology may also be applied to DNA alignments. The
      problem of finding the multiple alignment was investigated in the study by
      Bonizzoni and Vedova and Wang and Jiang, and proved to be a NP-hard (non
      deterministic polynomial-time hard) problem. The presented algorithm, called
      Immunological Multiple Sequence Alignment Algorithm (IMSA), incorporates two new
      strategies to create the initial population and specific ad hoc mutation
      operators. It is based on the 'weighted sum of pairs' as objective function, to
      evaluate a given candidate alignment. IMSA was tested using both classical
      benchmarks of BAliBASE (versions 1.0, 2.0 and 3.0), and experimental results
      indicate that it is comparable with state-of-the-art multiple alignment
      algorithms, in terms of quality of alignments, weighted Sums-of-Pairs (SP) and
      Column Score (CS) values. The main novelty of IMSA is its ability to generate
      more than a single suboptimal alignment, for every MSA instance; this behaviour
      is due to the stochastic nature of the algorithm and of the populations evolved
      during the convergence process. This feature will help the decision maker to
      assess and select a biologically relevant multiple sequence alignment. Finally,
      the designed algorithm can be used as a local search procedure to properly
      explore promising alignments of the search space.

PMID- 21071395
TI  - Arabidopsis thaliana telomeres exhibit euchromatic features.
AB  - Telomere function is influenced by chromatin structure and organization, which
      usually involves epigenetic modifications. We describe here the chromatin
      structure of Arabidopsis thaliana telomeres. Based on the study of six different
      epigenetic marks we show that Arabidopsis telomeres exhibit euchromatic features.
      In contrast, subtelomeric regions and telomeric sequences present at interstitial
      chromosomal loci are heterochromatic. Histone methyltransferases and the
      chromatin remodeling protein DDM1 control subtelomeric heterochromatin formation.
      Whereas histone methyltransferases are required for histone H3K9(2Me) and non-CpG
      DNA methylation, DDM1 directs CpG methylation but not H3K9(2Me) or non-CpG
      methylation. These results argue that both kinds of proteins participate in
      different pathways to reinforce subtelomeric heterochromatin formation.

PMID- 21071396
TI  - Critical association of ncRNA with introns.
AB  - It has been widely acknowledged that non-coding RNAs are master-regulators of
      genomic functions. However, the significance of the presence of ncRNA within
      introns has not received proper attention. ncRNA within introns are commonly
      produced through the post-splicing process and are specific signals of gene
      transcription events, impacting many other genes and modulating their expression.
      This study, along with the following discussion, details the association of
      thousands of ncRNAs--snoRNA, miRNA, siRNA, piRNA and long ncRNA--within human
      introns. We propose that such an association between human introns and ncRNAs has
      a pronounced synergistic effect with important implications for fine-tuning gene
      expression patterns across the entire genome.

PMID- 21071397
TI  - Hymenoptera Genome Database: integrated community resources for insect species of
      the order Hymenoptera.
AB  - The Hymenoptera Genome Database (HGD) is a comprehensive model organism database
      that caters to the needs of scientists working on insect species of the order
      Hymenoptera. This system implements open-source software and relational databases
      providing access to curated data contributed by an extensive, active research
      community. HGD contains data from 9 different species across ~200 million years
      in the phylogeny of Hymenoptera, allowing researchers to leverage genetic, genome
      sequence and gene expression data, as well as the biological knowledge of related
      model organisms. The availability of resources across an order greatly
      facilitates comparative genomics and enhances our understanding of the biology of
      agriculturally important Hymenoptera species through genomics. Curated data at
      HGD includes predicted and annotated gene sets supported with evidence tracks
      such as ESTs/cDNAs, small RNA sequences and GC composition domains. Data at HGD
      can be queried using genome browsers and/or BLAST/PSI-BLAST servers, and it may
      also be downloaded to perform local searches. We encourage the public to access
      and contribute data to HGD at: http://HymenopteraGenome.org.

PMID- 21071398
TI  - Thermodynamic contributions of single internal rA.dA, rC.dC, rG.dG and rU.dT
      mismatches in RNA/DNA duplexes.
AB  - The thermodynamic contributions of rA.dA, rC.dC, rG.dG and rU.dT single internal
      mismatches were measured for 54 RNA/DNA duplexes in a 1 M NaCl buffer using UV
      absorbance thermal denaturation. Thermodynamic parameters were obtained by
      fitting absorbance versus temperature profiles using the curve-fitting program
      Meltwin. The weighted average thermodynamic data were fit using singular value
      decomposition to determine the eight non-unique nearest-neighbor parameters for
      each internal mismatch. The new parameters predict the DeltaG degrees (37),
      DeltaH degrees  and melting temperature (T(m)) of duplexes containing these
      single mismatches within an average of 0.33 kcal/mol, 4.5 kcal/mol and 1.4
      degrees C, respectively. The general trend in decreasing stability for the single
      internal mismatches is rG.dG > rU.dT > rA.dA > rC.dC. The stability trend for the
      base pairs 5' of the single internal mismatch is rG.dC > rC.dG > rA.dT > rU.dA.
      The stability trend for the base pairs 3' of the single internal mismatch is
      rC.dG > rG.dC >> rA.dT > rU.dA. These nearest-neighbor values are now a part of a
      complete set of single internal mismatch thermodynamic parameters for RNA/DNA
      duplexes that are incorporated into the nucleic acid assay development software
      programs Visual oligonucleotide modeling platform (OMP) and ThermoBLAST.

PMID- 21071399
TI  - GenBank.
AB  - GenBank(r) is a comprehensive database that contains publicly available
      nucleotide sequences for more than 380,000 organisms named at the genus level or
      lower, obtained primarily through submissions from individual laboratories and
      batch submissions from large-scale sequencing projects, including whole genome
      shotgun (WGS) and environmental sampling projects. Most submissions are made
      using the web-based BankIt or standalone Sequin programs, and accession numbers
      are assigned by GenBank staff upon receipt. Daily data exchange with the European
      Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide
      coverage. GenBank is accessible through the NCBI Entrez retrieval system that
      integrates data from the major DNA and protein sequence databases along with
      taxonomy, genome, mapping, protein structure and domain information, and the
      biomedical journal literature via PubMed. BLAST provides sequence similarity
      searches of GenBank and other sequence databases. Complete bimonthly releases and
      daily updates of the GenBank database are available by FTP. To access GenBank and
      its related retrieval and analysis services, begin at the NCBI Homepage:
      www.ncbi.nlm.nih.gov.

PMID- 21071400
TI  - Sequence-dependent cooperative binding of p53 to DNA targets and its relationship
      to the structural properties of the DNA targets.
AB  - The prime mechanism by which p53 acts as a tumor suppressor is as a transcription
      factor regulating the expression of diverse downstream genes. The DNA-binding
      domain of p53 (p53DBD) interacts with defined DNA sites and is the main target
      for mutations in human primary tumors. Here, we show that the CWWG motif, found
      in the center of each consensus p53 half-site, is a key player in p53/DNA
      interactions. Gel-mobility-shift assays provide a unique opportunity to directly
      observe the various oligomeric complexes formed between p53DBD and its target
      sites. We demonstrate that p53DBD binds to p53 consensus sites containing CATG
      with relatively low cooperativity, as both dimers and tetramers, and with even
      lower cooperativity to such sites containing spacer sequences. p53DBD binds to
      sites containing CAAG and CTAG with measurable affinity only when imbedded in two
      contiguous p53 half-sites and only as tetramers (with very high cooperativity).
      There are three orders-of-magnitude difference in the cooperativity of
      interaction between sites differing in their non-contacted step, and further two
      orders-of-magnitude difference as a function of spacer sequences. By
      experimentally measuring the global structural properties of these sites, by
      cyclization kinetics of DNA minicircles, we correlate these differences with the
      torsional flexibility of the binding sites.

PMID- 21071401
TI  - The AddAB helicase-nuclease catalyses rapid and processive DNA unwinding using a
      single Superfamily 1A motor domain.
AB  - The oligomeric state of Superfamily I DNA helicases is the subject of
      considerable and ongoing debate. While models based on crystal structures imply
      that a single helicase core domain is sufficient for DNA unwinding activity,
      biochemical data from several related enzymes suggest that a higher order
      oligomeric species is required. In this work we characterize the helicase
      activity of the AddAB helicase-nuclease, which is involved in the repair of
      double-stranded DNA breaks in Bacillus subtilis. We show that the enzyme is
      functional as a heterodimer of the AddA and AddB subunits, that it is a rapid and
      processive DNA helicase, and that it catalyses DNA unwinding using one single
      stranded DNA motor of 3' -> 5' polarity located in the AddA subunit. The AddB
      subunit contains a second putative ATP-binding pocket, but this does not
      contribute to the observed helicase activity and may instead be involved in the
      recognition of recombination hotspot sequences.

PMID- 21071402
TI  - PSORTdb--an expanded, auto-updated, user-friendly protein subcellular
      localization database for Bacteria and Archaea.
AB  - The subcellular localization (SCL) of a microbial protein provides clues about
      its function, its suitability as a drug, vaccine or diagnostic target and aids
      experimental design. The first version of PSORTdb provided a valuable resource
      comprising a data set of proteins of known SCL (ePSORTdb) as well as pre-computed
      SCL predictions for proteomes derived from complete bacterial genomes (cPSORTdb).
      PSORTdb 2.0 (http://db.psort.org) extends user-friendly functionalities,
      significantly expands ePSORTdb and now contains pre-computed SCL predictions for
      all prokaryotes--including Archaea and Bacteria with atypical cell wall/membrane
      structures. cPSORTdb uses the latest version of the SCL predictor PSORTb (version
      3.0), with higher genome prediction coverage and functional improvements over
      PSORTb 2.0, which has been the most precise bacterial SCL predictor available.
      PSORTdb 2.0 is the first microbial protein SCL database reported to have an
      automatic updating mechanism to regularly generate SCL predictions for deduced
      proteomes of newly sequenced prokaryotic organisms. This updating approach uses a
      novel sequence analysis we developed that detects whether the microbe being
      analyzed has an outer membrane. This identification of membrane structure permits
      appropriate SCL prediction in an auto-updated fashion and allows PSORTdb to serve
      as a practical resource for genome annotation and prokaryotic research.

PMID- 21071403
TI  - Interpreting protein/DNA interactions: distinguishing specific from non-specific
      and electrostatic from non-electrostatic components.
AB  - We discuss the effectiveness of existing methods for understanding the forces
      driving the formation of specific protein-DNA complexes. Theoretical approaches
      using the Poisson-Boltzmann (PB) equation to analyse interactions between these
      highly charged macromolecules to form known structures are contrasted with an
      empirical approach that analyses the effects of salt on the stability of these
      complexes and assumes that release of counter-ions associated with the free DNA
      plays the dominant role in their formation. According to this counter-ion
      condensation (CC) concept, the salt-dependent part of the Gibbs energy of
      binding, which is defined as the electrostatic component, is fully entropic and
      its dependence on the salt concentration represents the number of ionic contacts
      present in the complex. It is shown that although this electrostatic component
      provides the majority of the Gibbs energy of complex formation and does not
      depend on the DNA sequence, the salt-independent part of the Gibbs energy-
      usually regarded as non-electrostatic--is sequence specific. The CC approach thus
      has considerable practical value for studying protein/DNA complexes, while
      practical applications of PB analysis have yet to demonstrate their merit.

PMID- 21071404
TI  - An SF1 affinity model to identify branch point sequences in human introns.
AB  - Splicing factor 1 (SF1) binds to the branch point sequence (BPS) of mammalian
      introns and is believed to be important for the splicing of some, but not all,
      introns. To help identify BPSs, particularly those that depend on SF1, we
      generated a BPS profile model in which SF1 binding affinity data, validated by
      branch point mapping, were iteratively incorporated into computational models. We
      searched a data set of 117,499 human introns for best matches to the SF1 Affinity
      Model above a threshold, and counted the number of matches at each intronic
      position. After subtracting a background value, we found that 87.9% of remaining
      high-scoring matches identified were located in a region upstream of 3'-splice
      sites where BPSs are typically found. Since U2AF65 recognizes the polypyrimidine
      tract (PPT) and forms a cooperative RNA complex with SF1, we combined the SF1
      model with a PPT model computed from high affinity binding sequences for U2AF65.
      The combined model, together with binding site location constraints, accurately
      identified introns bound by SF1 that are candidates for SF1-dependent splicing.

PMID- 21071405
TI  - ArrayExpress update--an archive of microarray and high-throughput sequencing
      based functional genomics experiments.
AB  - The ArrayExpress Archive (http://www.ebi.ac.uk/arrayexpress) is one of the three
      international public repositories of functional genomics data supporting
      publications. It includes data generated by sequencing or array-based
      technologies. Data are submitted by users and imported directly from the NCBI
      Gene Expression Omnibus. The ArrayExpress Archive is closely integrated with the
      Gene Expression Atlas and the sequence databases at the European Bioinformatics
      Institute. Advanced queries provided via ontology enabled interfaces include
      queries based on technology and sample attributes such as disease, cell types and
      anatomy.

PMID- 21071406
TI  - The RNA Modification Database, RNAMDB: 2011 update.
AB  - Since its inception in 1994, The RNA Modification Database (RNAMDB, http://rna
      mdb.cas.albany.edu/RNAmods/) has served as a focal point for information
      pertaining to naturally occurring RNA modifications. In its current state, the
      database employs an easy-to-use, searchable interface for obtaining detailed data
      on the 109 currently known RNA modifications. Each entry provides the chemical
      structure, common name and symbol, elemental composition and mass, CA registry
      numbers and index name, phylogenetic source, type of RNA species in which it is
      found, and references to the first reported structure determination and
      synthesis. Though newly transferred in its entirety to The RNA Institute, the
      RNAMDB continues to grow with two notable additions, agmatidine and 8
      methyladenosine, appended in the last year. The RNA Modification Database is
      staying up-to-date with significant improvements being prepared for inclusion
      within the next year and the following year. The expanded future role of The RNA
      Modification Database will be to serve as a primary information portal for
      researchers across the entire spectrum of RNA-related research.

PMID- 21071407
TI  - PROMISCUOUS: a database for network-based drug-repositioning.
AB  - The procedure of drug approval is time-consuming, costly and risky. Accidental
      findings regarding multi-specificity of approved drugs led to block-busters in
      new indication areas. Therefore, the interest in systematically elucidating new
      areas of application for known drugs is rising. Furthermore, the knowledge,
      understanding and prediction of so-called off-target effects allow a rational
      approach to the understanding of side-effects. With PROMISCUOUS we provide an
      exhaustive set of drugs (25,000), including withdrawn or experimental drugs,
      annotated with drug-protein and protein-protein relationships (21,500/104,000)
      compiled from public resources via text and data mining including manual
      curation. Measures of structural similarity for drugs as well as known side
      effects can be easily connected to protein-protein interactions to establish and
      analyse networks responsible for multi-pharmacology. This network-based approach
      can provide a starting point for drug-repositioning. PROMISCUOUS is publicly
      available at http://bioinformatics.charite.de/promiscuous.

PMID- 21071408
TI  - Phosphorylation of human Argonaute proteins affects small RNA binding.
AB  - Argonaute (Ago) proteins are highly conserved between species and constitute a
      direct-binding platform for small RNAs including short-interfering RNAs (siRNAs),
      microRNAs (miRNAs) and Piwi interacting RNAs (piRNAs). Small RNAs function as
      guides whereas Ago proteins are the actual mediators of gene silencing. Although
      the major steps in RNA-guided gene silencing have been elucidated, not much is
      known about Ago-protein regulation. Here we report a comprehensive analysis of
      Ago2 phosphorylation in human cells. We find that the highly conserved tyrosine
      Y529, located in the small RNA 5'-end-binding pocket of Ago proteins can be
      phosphorylated. By substituting Y529 with a negatively charged glutamate (E)
      mimicking a phosphorylated tyrosine, we show that small RNA binding is strongly
      reduced. Our data suggest that a negatively charged phospho-tyrosine generates a
      repulsive force that prevents efficient binding of the negatively charged 5'
      phosphate of the small RNA.

PMID- 21071409
TI  - Efficient preparation of internally modified single-molecule constructs using
      nicking enzymes.
AB  - Investigations of enzymes involved in DNA metabolism have strongly benefited from
      the establishment of single molecule techniques. These experiments frequently
      require elaborate DNA substrates, which carry chemical labels or nucleic acid
      tertiary structures. Preparing such constructs often represents a technical
      challenge: long modified DNA molecules are usually produced via multi-step
      processes, involving low efficiency intermolecular ligations of several
      fragments. Here, we show how long stretches of DNA (>50 bp) can be modified using
      nicking enzymes to produce complex DNA constructs. Multiple different chemical
      and structural modifications can be placed internally along DNA, in a specific
      and precise manner. Furthermore, the nicks created can be resealed efficiently
      yielding intact molecules, whose mechanical properties are preserved.
      Additionally, the same strategy is applied to obtain long single-strand overhangs
      subsequently used for efficient ligation of ss- to dsDNA molecules. This
      technique offers promise for a wide range of applications, in particular single
      molecule experiments, where frequently multiple internal DNA modifications are
      required.

PMID- 21071410
TI  - Characterization of L1 retrotransposition with high-throughput dual-luciferase
      assays.
AB  - Recent studies employing genome-wide approaches have provided an unprecedented
      view of the scope of L1 activities on structural variations in the human genome,
      and further reinforced the role of L1s as one of the major driving forces behind
      human genome evolution. The rapid identification of novel L1 elements by these
      high-throughput approaches demands improved L1 functional assays. However, the
      existing assays use antibiotic selection markers or fluorescent proteins as
      reporters; neither is amenable to miniaturization. To increase assay sensitivity
      and throughput, we have developed a third generation assay by using dual
      luciferase reporters, in which firefly luciferase is used as the
      retrotransposition indicator and Renilla luciferase is encoded on the same or
      separate plasmid for normalization. This novel assay is highly sensitive and has
      a broad dynamic range. Quantitative data with high signal-to-noise ratios can be
      obtained from 24- up to 96-well plates in 2-4 days after transfection. Using the
      dual-luciferase assays, we have characterized profiles of retrotransposition by
      various human and mouse L1 elements, and detailed the kinetics of L1
      retrotransposition in cultured cells. Its high-throughput and short assay
      timeframe make it well suited for routine tests as well as large-scale screening
      efforts.

PMID- 21071411
TI  - miRTarBase: a database curates experimentally validated microRNA-target
      interactions.
AB  - MicroRNAs (miRNAs), i.e. small non-coding RNA molecules (~22 nt), can bind to one
      or more target sites on a gene transcript to negatively regulate protein
      expression, subsequently controlling many cellular mechanisms. A current and
      curated collection of miRNA-target interactions (MTIs) with experimental support
      is essential to thoroughly elucidating miRNA functions under different conditions
      and in different species. As a database, miRTarBase has accumulated more than
      3500 MTIs by manually surveying pertinent literature after data mining of the
      text systematically to filter research articles related to functional studies of
      miRNAs. Generally, the collected MTIs are validated experimentally by reporter
      assays, western blot, or microarray experiments with overexpression or knockdown
      of miRNAs. miRTarBase curates 3576 experimentally verified MTIs between 657
      miRNAs and 2297 target genes among 17 species. miRTarBase contains the largest
      amount of validated MTIs by comparing with other similar, previously developed
      databases. The MTIs collected in the miRTarBase can also provide a large amount
      of positive samples to develop computational methods capable of identifying miRNA
      target interactions. miRTarBase is now available on
      http://miRTarBase.mbc.nctu.edu.tw/, and is updated frequently by continuously
      surveying research articles.

PMID- 21071412
TI  - The IMGT/HLA database.
AB  - It is 12 years since the IMGT/HLA database was first released, providing the HLA
      community with a searchable repository of highly curated HLA sequences. The HLA
      complex is located within the 6p21.3 region of human chromosome 6 and contains
      more than 220 genes of diverse function. Many of the genes encode proteins of the
      immune system and are highly polymorphic. The naming of these HLA genes and
      alleles and their quality control is the responsibility of the WHO Nomenclature
      Committee for Factors of the HLA System. Through the work of the HLA Informatics
      Group and in collaboration with the European Bioinformatics Institute, we are
      able to provide public access to this data through the web site
      http://www.ebi.ac.uk/imgt/hla/. Regular updates to the web site ensure that new
      and confirmatory sequences are dispersed to the HLA community, and the wider
      research and clinical communities.

PMID- 21071413
TI  - The BioGRID Interaction Database: 2011 update.
AB  - The Biological General Repository for Interaction Datasets (BioGRID) is a public
      database that archives and disseminates genetic and protein interaction data from
      model organisms and humans (http://www.thebiogrid.org). BioGRID currently holds
      347,966 interactions (170,162 genetic, 177,804 protein) curated from both high
      throughput data sets and individual focused studies, as derived from over 23,000
      publications in the primary literature. Complete coverage of the entire
      literature is maintained for budding yeast (Saccharomyces cerevisiae), fission
      yeast (Schizosaccharomyces pombe) and thale cress (Arabidopsis thaliana), and
      efforts to expand curation across multiple metazoan species are underway. The
      BioGRID houses 48,831 human protein interactions that have been curated from
      10,247 publications. Current curation drives are focused on particular areas of
      biology to enable insights into conserved networks and pathways that are relevant
      to human health. The BioGRID 3.0 web interface contains new search and display
      features that enable rapid queries across multiple data types and sources. An
      automated Interaction Management System (IMS) is used to prioritize, coordinate
      and track curation across international sites and projects. BioGRID provides
      interaction data to several model organism databases, resources such as Entrez
      Gene and other interaction meta-databases. The entire BioGRID 3.0 data collection
      may be downloaded in multiple file formats, including PSI MI XML. Source code for
      BioGRID 3.0 is freely available without any restrictions.

PMID- 21071414
TI  - tRNADB-CE 2011: tRNA gene database curated manually by experts.
AB  - We updated the tRNADB-CE by analyzing 939 complete and 1301 draft genomes of
      prokaryotes and eukaryotes, 171 complete virus genomes, 121 complete chloroplast
      genomes and approximately 230 million sequences obtained by metagenome analyses
      of 210 environmental samples. The 287 102 tRNA genes in total, and thus two times
      of the tRNA genes compiled previously, are compiled, in which sequence
      information, clover-leaf structure and results of sequence similarity and
      oligonucleotide-pattern search can be browsed. In order to pool collective
      knowledge with help from any experts in the tRNA research field, we included a
      column to which comments can be added on each tRNA gene. By compiling tRNAs of
      known prokaryotes with identical sequences, we found high phylogenetic
      preservation of tRNA sequences, especially at a phylum level. Furthermore, a
      large number of tRNAs obtained by metagenome analyses of environmental samples
      had sequences identical to those found in known prokaryotes. The identical
      sequence group, therefore, can be used as phylogenetic markers to clarify the
      microbial community structure of an ecosystem. The updated tRNADB-CE provided
      functions, with which users can obtain the phylotype-specific markers (e.g. genus
      specific markers) by themselves and clarify microbial community structures of
      ecosystems in detail. tRNADB-CE can be accessed freely at http://trna.nagahama-i
      bio.ac.jp.

PMID- 21071416
TI  - Effective--a database of predicted secreted bacterial proteins.
AB  - Protein secretion is a key virulence mechanism of pathogenic and symbiotic
      bacteria, which makes the investigation of secreted proteins ('effectors')
      crucial for understanding the molecular bacterium-host interactions. Effective
      (http://effectors.org) is a database of predicted bacterial secreted proteins,
      implementing two complementary prediction strategies for protein secretion: the
      identification of eukaryotic-like protein domains and the recognition of signal
      peptides in amino acid sequences. The Effective web portal provides user-friendly
      tools for browsing and retrieving comprehensive precalculated predictions for
      whole bacterial genomes as well as for the interactive prediction of effectors in
      user-provided protein sequences.

PMID- 21071415
TI  - Genome-wide detection of a TFIID localization element from an initial human
      disease mutation.
AB  - Eukaryotic core promoters are often characterized by the presence of consensus
      motifs such as the TATA box or initiator elements, which attract and direct the
      transcriptional machinery to the transcription start site. However, many human
      promoters have none of the known core promoter motifs, suggesting that
      undiscovered promoter motifs exist in the genome. We previously identified a
      mutation in the human Ankyrin-1 (ANK-1) promoter that causes the disease ankyrin
      deficient Hereditary Spherocytosis (HS). Although the ANK-1 promoter is CpG rich,
      no discernable basal promoter elements had been identified. We showed that the HS
      mutation disrupted the binding of the transcription factor TFIID, the major
      component of the pre-initiation complex. We hypothesized that the mutation
      identified a candidate promoter element with a more widespread role in gene
      regulation. We examined 17,181 human promoters for the experimentally validated
      binding site, called the TFIID localization sequence (DLS) and found three times
      as many promoters containing DLS than TATA motifs. Mutational analyses of DLS
      sequences confirmed their functional significance, as did the addition of a DLS
      site to a minimal Sp1 promoter. Our results demonstrate that novel promoter
      elements can be identified on a genome-wide scale through observations of
      regulatory disruptions that cause human disease.

PMID- 21071417
TI  - PCDDB: the Protein Circular Dichroism Data Bank, a repository for circular
      dichroism spectral and metadata.
AB  - The Protein Circular Dichroism Data Bank (PCDDB) is a public repository that
      archives and freely distributes circular dichroism (CD) and synchrotron radiation
      CD (SRCD) spectral data and their associated experimental metadata. All entries
      undergo validation and curation procedures to ensure completeness, consistency
      and quality of the data included. A web-based interface enables users to browse
      and query sample types, sample conditions, experimental parameters and provides
      spectra in both graphical display format and as downloadable text files. The
      entries are linked, when appropriate, to primary sequence (UniProt) and
      structural (PDB) databases, as well as to secondary databases such as the Enzyme
      Commission functional classification database and the CATH fold classification
      database, as well as to literature citations. The PCDDB is available at:
      http://pcddb.cryst.bbk.ac.uk.

PMID- 21071418
TI  - Alpha-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes.
AB  - Alternative splicing enables higher eukaryotes to increase their repertoire of
      proteins derived from a restricted number of genes. However, the possibility that
      functional diversity may also be augmented by splicing between adjacent genes has
      been largely neglected. Here, we show that the human melanocortin 1 receptor
      (MC1R) gene, a critical component of the facultative skin pigmentation system,
      has a highly complex and inefficient poly(A) site which is instrumental in
      allowing intergenic splicing between this locus and its immediate downstream
      neighbour tubulin-beta-III (TUBB3). These transcripts, which produce two distinct
      protein isoforms localizing to the plasma membrane and the endoplasmic reticulum,
      seem to be restricted to humans as no detectable chimeric mRNA could be found in
      MC1R expressing mouse melanocytes. Significantly, treatment with the MC1R agonist
      alpha-MSH or activation of the stress response kinase p38-MAPK, both key
      molecules associated with ultraviolet radiation dermal insult and subsequent skin
      tanning, result in a shift in expression from MC1R in favour of chimeric MC1R
      TUBB3 isoforms in cultured melanocytes. We propose that these chimeric proteins
      serve to equip melanocytes with novel cellular phenotypes required as part of the
      pigmentation response.

PMID- 21071419
TI  - Digital MDA for enumeration of total nucleic acid contamination.
AB  - Multiple displacement amplification (MDA) is an isothermal, sequence-independent
      method for the amplification of high molecular weight DNA that is driven by phi29
      DNA polymerase (DNAP). Here we report digital MDA (dMDA), an ultrasensitive
      method for quantifying nucleic acid fragments of unknown sequence. We use the new
      assay to show that our custom phi29 DNAP preparation is free of contamination at
      the limit of detection of the dMDA assay (1 contaminating molecule per assay
      microliter). Contamination in commercially available preparations is also
      investigated. The results of the dMDA assay provide strong evidence that the so
      called 'template-independent' MDA background can be attributed to high-molecular
      weight contaminants and is not primer-derived in the commercial kits tested. dMDA
      is orders of magnitude more sensitive than PCR-based techniques for detection of
      microbial genomic DNA fragments and opens up new possibilities for the
      ultrasensitive quantification of DNA fragments in a wide variety of application
      areas using MDA chemistry and off-the-shelf hardware developed for digital PCR.

PMID- 21071420
TI  - LocDB: experimental annotations of localization for Homo sapiens and Arabidopsis
      thaliana.
AB  - LocDB is a manually curated database with experimental annotations for the
      subcellular localizations of proteins in Homo sapiens (HS, human) and Arabidopsis
      thaliana (AT, thale cress). Currently, it contains entries for 19,604 UniProt
      proteins (HS: 13,342; AT: 6262). Each database entry contains the experimentally
      derived localization in Gene Ontology (GO) terminology, the experimental
      annotation of localization, localization predictions by state-of-the-art methods
      and, where available, the type of experimental information. LocDB is searchable
      by keyword, protein name and subcellular compartment, as well as by identifiers
      from UniProt, Ensembl and TAIR resources. In comparison to other public
      databases, LocDB as a resource adds about 10,000 experimental localization
      annotations for HS proteins and ~900 for AS proteins. Over 40% of the proteins in
      LocDB have multiple localization annotations providing a better platform for
      development of new multiple localization prediction methods with higher coverage
      and accuracy. Links to all referenced databases are provided. LocDB will be
      updated regularly by our group (available at:
      http://www.rostlab.org/services/locDB).

PMID- 21071421
TI  - A conserved structure within the HIV gag open reading frame that controls
      translation initiation directly recruits the 40S subunit and eIF3.
AB  - Translation initiation on HIV genomic RNA relies on both cap and Internal
      Ribosome Entry Site (IRES) dependant mechanisms that are regulated throughout the
      cell cycle. During a unique phenomenon, the virus recruits initiation complexes
      through RNA structures located within Gag coding sequence, downstream of the
      initiation codon. We analyzed initiation complexes paused on the HIV-2 gag IRES
      and revealed that they contain all the canonical initiation factors except eIF4E
      and eIF1. We report that eIF3 and the small ribosomal subunit bind HIV RNA within
      gag open reading frame. We thus propose a novel two step model whereby the
      initial event is the formation of a ternary eIF3/40S/IRES complex. In a second
      step, dependent on most of the canonical initiation factors, the complex is
      rearranged to transfer the ribosome on the initiation codons. The absolute
      requirement of this large structure for HIV translation defines a new function
      for a coding region. Moreover, the level of information compaction within this
      viral genome reveals an additional level of evolutionary constraint on the coding
      sequence. The conservation of this IRES and its properties in rapidly evolving
      viruses suggest an important role in the virus life cycle and highlight an
      attractive new therapeutic target.

PMID- 21071422
TI  - ConsensusPathDB: toward a more complete picture of cell biology.
AB  - ConsensusPathDB is a meta-database that integrates different types of functional
      interactions from heterogeneous interaction data resources. Physical protein
      interactions, metabolic and signaling reactions and gene regulatory interactions
      are integrated in a seamless functional association network that simultaneously
      describes multiple functional aspects of genes, proteins, complexes, metabolites,
      etc. With 155,432 human, 194,480 yeast and 13,648 mouse complex functional
      interactions (originating from 18 databases on human and eight databases on yeast
      and mouse interactions each), ConsensusPathDB currently constitutes the most
      comprehensive publicly available interaction repository for these species. The
      Web interface at http://cpdb.molgen.mpg.de offers different ways of utilizing
      these integrated interaction data, in particular with tools for visualization,
      analysis and interpretation of high-throughput expression data in the light of
      functional interactions and biological pathways.

PMID- 21071423
TI  - A series of PDB related databases for everyday needs.
AB  - The Protein Data Bank (PDB) is the world-wide repository of macromolecular
      structure information. We present a series of databases that run parallel to the
      PDB. Each database holds one entry, if possible, for each PDB entry. DSSP holds
      the secondary structure of the proteins. PDBREPORT holds reports on the structure
      quality and lists errors. HSSP holds a multiple sequence alignment for all
      proteins. The PDBFINDER holds easy to parse summaries of the PDB file content,
      augmented with essentials from the other systems. PDB_REDO holds re-refined, and
      often improved, copies of all structures solved by X-ray. WHY_NOT summarizes why
      certain files could not be produced. All these systems are updated weekly. The
      data sets can be used for the analysis of properties of protein structures in
      areas ranging from structural genomics, to cancer biology and protein design.

PMID- 21071424
TI  - AREsite: a database for the comprehensive investigation of AU-rich elements.
AB  - AREsite is an online resource for the detailed investigation of AU-rich elements
      (ARE) in vertebrate mRNA 3'-untranslated regions (UTRs). AREs are one of the most
      prominent cis-acting regulatory elements found in 3'-UTRs of mRNAs. Various ARE
      binding proteins that possess RNA stabilizing or destabilizing functions are
      recruited by sequence-specific motifs. Recent findings suggest an essential role
      of the structural mRNA context in which these sequence motifs are embedded.
      AREsite is the first database that allows to quantify the structuredness of ARE
      motif sites in terms of opening energies and accessibility probabilities.
      Moreover, we also provide a detailed phylogenetic analysis of ARE motifs and
      incorporate information about experimentally validated targets of the ARE-binding
      proteins TTP, HuR and Auf1. The database is publicly available at:
      http://rna.tbi.univie.ac.at/AREsite.

PMID- 21071425
TI  - The ARiBo tag: a reliable tool for affinity purification of RNAs under native
      conditions.
AB  - Although RNA-based biological processes and therapeutics have gained increasing
      interest, purification of in vitro transcribed RNA generally relies on gel-based
      methods that are time-consuming, tedious and denature the RNA. Here, we present a
      reliable procedure for affinity batch purification of RNA, which exploits the
      high-affinity interaction between the boxB RNA and the N-peptide from
      bacteriophage lambda. The RNA of interest is synthesized with an ARiBo tag, which
      consists of an activatable ribozyme (the glmS ribozyme) and the lambdaBoxB RNA.
      This ARiBo-fusion RNA is initially captured on Glutathione-Sepharose resin via a
      GST/lambdaN-fusion protein, and the RNA of interest is subsequently eluted by
      ribozyme self-cleavage using glucosamine-6-phosphate. Several GST/lambdaN-fusion
      proteins and ARiBo tags were tested to optimize RNA yield and purity. The
      optimized procedure enables one to quickly obtain (3 h) highly pure RNA (>99%)
      under native conditions and with yields comparable to standard denaturing gel
      based protocols. It is widely applicable to a variety of RNAs, including
      riboswitches, ribozymes and microRNAs. In addition, it can be easily adapted to a
      wide range of applications that require RNA purification and/or immobilization,
      including isolation of RNA-associated complexes from living cells and high
      throughput applications.

PMID- 21071426
TI  - PRIDB: a Protein-RNA interface database.
AB  - The Protein-RNA Interface Database (PRIDB) is a comprehensive database of protein
      RNA interfaces extracted from complexes in the Protein Data Bank (PDB). It is
      designed to facilitate detailed analyses of individual protein-RNA complexes and
      their interfaces, in addition to automated generation of user-defined data sets
      of protein-RNA interfaces for statistical analyses and machine learning
      applications. For any chosen PDB complex or list of complexes, PRIDB rapidly
      displays interfacial amino acids and ribonucleotides within the primary sequences
      of the interacting protein and RNA chains. PRIDB also identifies ProSite motifs
      in protein chains and FR3D motifs in RNA chains and provides links to these
      external databases, as well as to structure files in the PDB. An integrated JMol
      applet is provided for visualization of interacting atoms and residues in the
      context of the 3D complex structures. The current version of PRIDB contains
      structural information regarding 926 protein-RNA complexes available in the PDB
      (as of 10 October 2010). Atomic- and residue-level contact information for the
      entire data set can be downloaded in a simple machine-readable format. Also,
      several non-redundant benchmark data sets of protein-RNA complexes are provided.
      The PRIDB database is freely available online at
      http://bindr.gdcb.iastate.edu/PRIDB.

PMID- 21071427
TI  - Dual N- and C-terminal processing of citrus chlorophyllase precursor within the
      plastid membranes leads to the mature enzyme.
AB  - Chl, the central player in harvesting light energy for photosynthesis, is
      enzymatically degraded during natural turnover, leaf senescence, fruit ripening
      or following biotic/abiotic stress induction. The photodynamic properties of Chl
      and its metabolites call for tight regulation of the catabolic pathway enzymes to
      avoid accumulation of intermediate breakdown products. Chlorophyllase, the Chl
      dephytilation enzyme, was previously demonstrated to be an initiator of Chl
      breakdown when transcriptionally induced to be expressed during ethylene-induced
      citrus fruit color break or when heterologously expressed in different plant
      systems. Citrus chlorophyllase was previously shown to be translated as a
      precursor protein, which is subsequently post-translationally processed to a
      mature form. We demonstrate that maturation of citrus chlorophyllase involves
      dual N- and C-terminal processing which appear to be rate-limiting post
      translational events when chlorophyllase expression levels are high. The
      chlorophyllase precursor and intermediate forms were shown to be of transient
      nature, while the mature form accumulates over time, suggesting that processing
      may be involved in post-translational regulation of enzyme in vivo function. This
      notion is further supported by the finding that neither N- nor C-terminal
      processed domains are essential for chloroplast targeting of the enzyme, and that
      both processing events occur within the chloroplast membranes. Studies on the
      processing of chlorophyllase versions truncated at the N- or C-termini or mutated
      to abolish C-terminal processing suggest that each of the processing events is
      independent. Dual N- and C-terminal processing, not involving an organellar
      targeting signal, has rarely been documented in plants and is unique for a
      plastid protein.

PMID- 21071428
TI  - Post-translational modifications in secreted peptide hormones in plants.
AB  - More than a dozen secreted peptides are now recognized as important hormones that
      coordinate and specify cellular functions in plants. Recent evidence has shown
      that secreted peptide hormones often undergo post-translational modification and
      proteolytic processing, which are critical for their function. Such 'small post
      translationally modified peptide hormones' constitute one of the largest groups
      of peptide hormones in plants. This short review highlights recent progress in
      research on post-translationally modified peptide hormones, with particular
      emphasis on their structural characteristics and modification mechanisms.

PMID- 21071429
TI  - Profiles of purine metabolism in leaves and roots of Camellia sinensis seedlings.
AB  - To determine the metabolic profiles of purine nucleotides and related compounds
      in leaves and roots of tea (Camellia sinensis), we studied the in situ metabolic
      fate of 10 different (14)C-labeled precursors in segments from tea seedlings. The
      activities of key enzymes in tea leaf extracts were also investigated. The rates
      of uptake of purine precursors were greater in leaf segments than in root
      segments. Adenine and adenosine were taken up more rapidly than other purine
      bases and nucleosides. Xanthosine was slowest. Some adenosine, guanosine and
      inosine was converted to nucleotides by adenosine kinase and inosine/guanosine
      kinase, but these compounds were easily hydrolyzed, and adenine, guanine and
      hypoxanthine were generated. These purine bases were salvaged by adenine
      phosphoribosyltransferase and hypoxanthine/guanine phosphoribosyltransferase.
      Salvage activity of adenine and adenosine was high, and they were converted
      exclusively to nucleotides. Inosine and hypoxanthine were salvaged to a lesser
      extent. In situ (14)C-tracer experiments revealed that xanthosine and xanthine
      were not salvaged, although xanthine phosphoribosyltransferase activity was found
      in tea extracts. Only some deoxyadenosine and deoxyguanosine was salvaged and
      utilized for DNA synthesis. However, most of these deoxynucleosides were
      hydrolyzed to adenine and guanine and then utilized for RNA synthesis. Purine
      alkaloid biosynthesis in leaves is much greater than in roots. In situ
      experiments indicate that adenosine, adenine, guanosine, guanine and inosine are
      better precursors than xanthosine, which is a direct precursor of a major pathway
      of caffeine biosynthesis. Based on these results, possible routes of purine
      metabolism are discussed.

PMID- 21071431
TI  - Resveratrol blocks Akt activation in angiotensin II- or EGF-stimulated vascular
      smooth muscle cells in a redox-independent manner.
AB  - AIMS: Resveratrol (RV), an antioxidant, inhibits angiotensin II (Ang II)-induced
      hypertrophy and Ang II- or epidermal growth factor (EGF)-induced Akt
      phosphorylation in rat vascular smooth muscle cells (VSMCs). Both signalling
      pathways are reported to utilize reactive oxygen species (ROS). The aim of this
      study was to show whether RV reduces the ROS level in Ang II- or EGF-activated
      VSMCs and whether reduction of ROS causes the impeded signalling towards Akt in
      the presence of RV. METHODS AND RESULTS: We show here that RV reduces
      intracellular ROS and extracellular H2O2 release from VSMCs as measured using
      2',7'-dichlorodihydrofluorescein-diacetate and Amplex RedTM. Since NADPH oxidases
      (Nox) 1 and 4 are major ROS sources in VSMCs, we examined their need for Akt
      phosphorylation in response to Ang II or EGF. Experiments using the blocking
      peptide gp91ds-tat verified a role for Nox1 in Ang II signalling towards Akt, but
      excluded a role for Nox1 in the respective EGF signalling. A small interfering
      RNA-mediated knock-down of Nox4 showed that Nox4 was not required for Ang II- or
      EGF-induced Akt phosphorylation. Use of the flavoprotein inhibitor
      diphenyleneiodonium, N-acetyl-cysteine, and non-antioxidant RV derivatives
      revealed that the antioxidant capacity of RV is not required for the inhibition
      of Akt phosphorylation, in both rat and human VSMCs. CONCLUSION: Thus, although
      RV acts as an antioxidant, the antihypertrophic response of RV in VSMCs and the
      signalling downstream of the EGF receptor towards Akt seem to be largely redox
      independent.

PMID- 21071433
TI  - Gathering time-series data for evaluating behavior-change campaigns in developing
      countries: reactivity of diaries and interviews.
AB  - Gathering time-series data of behaviors and psychological variables is important
      to understand, guide, and evaluate behavior-change campaigns and other change
      processes. However, repeated measurement can affect the phenomena investigated,
      particularly frequent face-to-face interviews, which are often the only option in
      developing countries. This article presents three intervention control studies to
      investigate this issue. Daily diaries in Cuba did not affect behavior or
      attitudes for persons with intervention but reduced attitudes for persons without
      intervention. Reactivity of face-to-face interviews in Bolivia was negligible if
      applied weekly, but strong if applied twice per week. The article concludes with
      recommendations for gathering time-series data in developing countries.

PMID- 21071432
TI  - Haploinsufficiency of the murine Col3a1 locus causes aortic dissection: a novel
      model of the vascular type of Ehlers-Danlos syndrome.
AB  - AIMS: The vascular type of Ehlers-Danlos syndrome (EDS IV) is an autosomal
      dominant disorder characterized by thin translucent skin and extensive bruising.
      Patients with EDS IV have reduced life expectancy (median 45-50 years) due to
      spontaneous rupture of arteries (particularly large arteries) or bowel. EDS IV
      results from mutation of the COL3A1 gene, which encodes the pro-alpha(1) chains
      of type III collagen that is secreted into the extracellular matrix, e.g. by
      smooth muscle cells. A mouse model of EDS IV produced by targeted ablation of
      Col3a1 has been of limited use as only 10% of homozygous animals survive to
      adulthood, whereas heterozygous animals do not die from arterial rupture. We
      report a novel, exploitable model of EDS IV in a spontaneously generated mouse
      line. METHODS AND RESULTS: Mice were identified by predisposition to sudden,
      unexpected death from dissection of the thoracic aorta. Aortic dissection
      inheritance was autosomal-dominant, presented at an early age (median, 6 weeks)
      with incomplete penetrance, and had a similar sex ratio bias as EDS IV (2:1,
      male:female). Molecular genetic analysis demonstrated that the causal mutation is
      a spontaneous 185 kb deletion, including the promoter region and exons 1-39, of
      the Col3a1 gene. As in EDS IV, aortic dissection was not associated with elevated
      blood pressure, aneurysm formation, or infection, but may result from aberrant
      collagen fibrillogenesis within the aortic wall. CONCLUSION: This novel,
      exploitable mouse line that faithfully models the vascular aspects of human EDS
      IV provides an important new tool for advancing understanding of EDS IV and of
      aortic dissection in general.

PMID- 21071434
TI  - Palliative care communication curriculum: what can students learn from an
      unfolding case?
AB  - Limited attention to palliative care communication training is offered to medical
      students. In this work, we pursued unfolding case responses and what they
      indicated about student tendencies to use palliative care communication as well
      as what medical students can learn from their own reflective practice about
      palliative care. Findings showed an overwhelming trend for students to avoid
      palliative care communication or inclusion of topics including advance
      directives, place of care, family support, and dying. Instead, students relied
      heavily on the SPIKES protocol, communication that was strategically vague and
      ambiguous, and discussions that centered on specialty care and referral. In
      reflecting on their own case study responses, students noted an absence of direct
      communication about prognosis, no coordination of care, late hospice entry, and
      patient pain resulting from communication inefficacies. Future research should
      focus on the development of formal and adaptive curriculum structures to address
      these communication needs.

PMID- 21071435
TI  - Hospice utilization and end-of-life care decision making of African Americans.
AB  - Multiple, complex factors influence end-of-life (EOL) decisions for all persons.
      In the African American population, these factors include history of disparities
      and discrimination in health care, which may affect the individual and the
      family, family system beliefs, values, and practices, and health care system
      issues. Family dynamics have an especially important role in treatment decisions
      for loved ones with advanced disease. A family systems framework can guide the
      clinicians in appreciating care needs and preferences at EOL. Understanding why
      so many African Americans choose aggressive and often burdensome care, even at
      the expense of suffering, is important for communication about options at the EOL
      and the delivery of quality care at the EOL.

PMID- 21071436
TI  - Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys
      48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are
      required for degradation.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are large, ubiquitously
      expressed, endoplasmic reticulum membrane proteins that form tetrameric IP(3) and
      Ca(2+)-gated Ca(2+) channels. Endogenous IP(3)Rs provide very appealing tools for
      studying the ubiquitin-proteasome pathway in intact mammalian cells because, upon
      activation, they are rapidly ubiquitinated and degraded. Using mass spectrometry,
      we previously examined the ubiquitination of IP(3)R1 in alphaT3-1 pituitary
      gonadotrophs and found that IP(3)R1 ubiquitination is highly complex, with
      receptors being modified at multiple sites by monoubiquitin and polyubiquitin
      chains formed through both Lys-48 and Lys-63 linkages (Sliter, D. A., Kubota, K.,
      Kirkpatrick, D. S., Alzayady, K. J., Gygi, S. P., and Wojcikiewicz, R. J. H.
      (2008) J. Biol. Chem. 283, 35319-35328). Here, we have extended these studies to
      determine whether IP(3)R2 and IP(3)R3 are similarly modified and if
      ubiquitination is cell type-dependent. Using mass spectrometry and linkage
      specific ubiquitin antibodies, we found that all IP(3)R types are subject to
      ubiquitination at approximately the same locations and that, independent of cell
      type, IP(3)Rs are modified by monoubiquitin and Lys-48- and Lys-63-linked
      ubiquitin chains, although in differing proportions. Remarkably, the attached Lys
      48- and Lys-63-linked ubiquitin chains are homogeneous and are segregated to
      separate IP(3)R subunits, and Lys-48-linked ubiquitin chains, but not Lys-63
      linked chains, are required for IP(3)R degradation. Together, these data provide
      unique insight into the complexities of ubiquitination of an endogenous ubiquitin
      proteasome pathway substrate in unperturbed mammalian cells. Importantly,
      although Lys-48-linked ubiquitin chains appear to trigger proteasomal
      degradation, the presence of Lys-63-linked ubiquitin chains suggests that
      ubiquitination of IP(3)Rs may have physiological consequences beyond signaling
      for degradation.

PMID- 21071437
TI  - Role of MSK1 in the malignant phenotype of Ras-transformed mouse fibroblasts.
AB  - Activated by the RAS-MAPK signaling pathway, MSK1 is recruited to immediate-early
      gene (IEG) regulatory regions, where it phosphorylates histone H3 at Ser-10 or
      Ser-28. Chromatin remodelers and modifiers are then recruited by 14-3-3 proteins,
      readers of phosphoserine marks, leading to the occupancy of IEG promoters by the
      initiation-engaged form of RNA polymerase II and the onset of transcription. In
      this study, we show that this mechanism of IEG induction, initially elucidated in
      parental 10T1/2 murine fibroblast cells, applies to metastatic Hras1-transformed
      Ciras-3 cells. As the RAS-MAPK pathway is constitutively activated in Ciras-3
      cells, MSK1 activity and phosphorylated H3 steady-state levels are elevated. We
      found that steady-state levels of the IEG products AP-1 and COX-2 were also
      elevated in Ciras-3 cells. When MSK1 activity was inhibited or MSK1 expression
      was knocked down in Ciras-3 cells, the induction of IEG expression and the steady
      state levels of COX-2, FRA-1, and JUN were greatly reduced. Furthermore, MSK1
      knockdown Ciras-3 cells lost their malignant phenotype, as reflected by the
      absence of anchorage-independent growth.

PMID- 21071438
TI  - DGK1-encoded diacylglycerol kinase activity is required for phospholipid
      synthesis during growth resumption from stationary phase in Saccharomyces
      cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, triacylglycerol mobilization for
      phospholipid synthesis occurs during growth resumption from stationary phase, and
      this metabolism is essential in the absence of de novo fatty acid synthesis. In
      this work, we provide evidence that DGK1-encoded diacylglycerol kinase activity
      is required to convert triacylglycerol-derived diacylglycerol to phosphatidate
      for phospholipid synthesis. Cells lacking diacylglycerol kinase activity (e.g.
      dgk1Delta mutation) failed to resume growth in the presence of the fatty acid
      synthesis inhibitor cerulenin. Lipid analysis data showed that dgk1Delta mutant
      cells did not mobilize triacylglycerol for membrane phospholipid synthesis and
      accumulated diacylglycerol. The dgk1Delta phenotypes were partially complemented
      by preventing the formation of diacylglycerol by the PAH1-encoded phosphatidate
      phosphatase and by channeling diacylglycerol to phosphatidylcholine via the
      Kennedy pathway. These observations, coupled to an inhibitory effect of
      dioctanoyl-diacylglycerol on the growth of wild type cells, indicated that
      diacylglycerol kinase also functions to alleviate diacylglycerol toxicity.

PMID- 21071439
TI  - ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1
      (mTORC1).
AB  - The Ras/mitogen-activated protein kinase (MAPK) pathway regulates a variety of
      cellular processes by activating specific transcriptional and translational
      programs. Ras/MAPK signaling promotes mRNA translation and protein synthesis, but
      the exact molecular mechanisms underlying this regulation remain poorly
      understood. Increasing evidence suggests that the mammalian target of rapamycin
      (mTOR) plays an essential role in this process. Here, we show that Raptor, an
      essential scaffolding protein of the mTOR complex 1 (mTORC1), becomes
      phosphorylated on proline-directed sites following activation of the Ras/MAPK
      pathway. We found that ERK1 and ERK2 interact with Raptor in cells and mediate
      its phosphorylation in vivo and in vitro. Using mass spectrometry and
      phosphospecific antibodies, we found three proline-directed residues within
      Raptor, Ser(8), Ser(696), and Ser(863), which are directly phosphorylated by
      ERK1/2. Expression of phosphorylation-deficient alleles of Raptor revealed that
      phosphorylation of these sites by ERK1/2 normally promotes mTORC1 activity and
      signaling to downstream substrates, such as 4E-BP1. Our data provide a novel
      regulatory mechanism by which mitogenic and oncogenic activation of the Ras/MAPK
      pathway promotes mTOR signaling.

PMID- 21071440
TI  - Recruitment of RelB to the Csf2 promoter enhances RelA-mediated transcription of
      granulocyte-macrophage colony-stimulating factor.
AB  - Tumor necrosis factor (TNF) induces expression of granulocyte-macrophage colony
      stimulating factor (GM-CSF) but lymphotoxin beta (LTbeta) does not. Here we
      report that priming of cells with agonistic LTbeta receptor antibody
      synergistically enhanced TNF-induced GM-CSF expression. The LTbeta priming
      process was not due to an increase in TNF-mediated nuclear translocation of p65,
      p65 DNA binding, or NF-kappaB transactivational activity. The synergistic effect
      of LTbeta priming was not observed with other TNF-responsive genes such as Ccl2
      or RelB, which suggested that this effect was not a general increase in TNF
      signaling. Furthermore, RelB and p65 were both independently recruited to the GM
      CSF promoter when cells were primed with LTbeta followed by TNF treatment. As a
      consequence, an increase in both chromatin accessibility and the recruitment of
      RNA polymerase II were observed to the GM-CSF promoter. Taken together, these
      findings suggested that LTbeta signaling amplified TNF-mediated GM-CSF expression
      by facilitating chromatin access and the co-recruitment of RNA polymerase II to
      increase gene transcription. Moreover, the novel priming process described here
      underscores the complexity of the interactions between the classical and
      alternative NF-kappaB signaling pathways.

PMID- 21071441
TI  - Axonal degeneration is blocked by nicotinamide mononucleotide adenylyltransferase
      (Nmnat) protein transduction into transected axons.
AB  - Axonal degeneration is an early and important component of many neurological
      disorders. Overexpression of nicotinamide mononucleotide adenylyltransferase
      (Nmnat), a component of the slow Wallerian degeneration (Wld(s)) protein,
      protects axons from a variety of insults. We found that transduction of Nmnat
      protein into severed axons via virus-like particles prevented axonal
      degeneration. The post-injury efficacy of Nmnat indicates that its protective
      effects occur locally within the axon and provides an opportunity to develop
      novel agents to treat axonal damage.

PMID- 21071442
TI  - Fluorescence of phytochrome adducts with synthetic locked chromophores.
AB  - We performed steady state fluorescence measurements with phytochromes Agp1 and
      Agp2 of Agrobacterium tumefaciens and three mutants in which photoconversion is
      inhibited. These proteins were assembled with the natural chromophore biliverdin
      (BV), with phycoerythrobilin (PEB), which lacks a double bond in the ring C-D
      connecting methine bridge, and with synthetic bilin derivatives in which the ring
      C-D-connecting methine bridge is locked. All PEB and locked chromophore adducts
      are photoinactive. According to fluorescence quantum yields, the adducts may be
      divided into four different groups: wild type BV adducts exhibiting a weak
      fluorescence, mutant BV adducts with about 10-fold enhanced fluorescence, adducts
      with locked chromophores in which the fluorescence quantum yields are around
      0.02, and PEB adducts with a high quantum yield of around 0.5. Thus, the strong
      fluorescence of the PEB adducts is not reached by the locked chromophore adducts,
      although the photoconversion energy dissipation pathway is blocked. We therefore
      suggest that ring D of the bilin chromophore, which contributes to the extended
      pi-electron system of the locked chromophores, provides an energy dissipation
      pathway that is independent on photoconversion.

PMID- 21071443
TI  - Activation of vinculin induced by cholinergic stimulation regulates contraction
      of tracheal smooth muscle tissue.
AB  - Vinculin localizes to membrane adhesion junctions where it links actin filaments
      to the extracellular matrix by binding to the integrin-binding protein talin at
      its head domain (Vh) and to actin filaments at its tail domain (Vt). Vinculin can
      assume an inactive (closed) conformation in which Vh and Vt bind to each other,
      masking the binding sites for actin and talin, and an active (open) conformation
      in which the binding sites for talin and actin are exposed. We hypothesized that
      the contractile activation of smooth muscle tissues might regulate the activation
      of vinculin and thereby contribute to the regulation of contractile tension.
      Stimulation of tracheal smooth muscle tissues with acetylcholine (ACh) induced
      the recruitment of vinculin to cell membrane and its interaction with talin and
      increased the phosphorylation of membrane-localized vinculin at the C-terminal
      Tyr-1065. Expression of recombinant vinculin head domain peptide (Vh) in smooth
      muscle tissues, but not the talin-binding deficient mutant head domain, VhA50I,
      inhibited the ACh-induced recruitment of endogenous vinculin to the membrane and
      the interaction of vinculin with talin and also inhibited vinculin
      phosphorylation. Expression of Vh peptide also inhibited ACh-induced smooth
      muscle contraction and inhibited ACh-induced actin polymerization; however, it
      did not affect myosin light chain phosphorylation, which is necessary for cross
      bridge cycling. Inactivation of RhoA inhibited vinculin activation in response to
      ACh. We conclude that ACh stimulation regulates vinculin activation in tracheal
      smooth muscle via RhoA and that vinculin activation contributes to the regulation
      of active tension by facilitating connections between actin filaments and talin
      integrin adhesion complexes and by mediating the initiation of actin
      polymerization.

PMID- 21071444
TI  - Myosin binding protein C interaction with actin: characterization and mapping of
      the binding site.
AB  - Myosin binding protein C (MyBPC) is a multidomain protein associated with the
      thick filaments of striated muscle. Although both structural and regulatory roles
      have been proposed for MyBPC, its interactions with other sarcomeric proteins
      remain obscure. The current study was designed to examine the actin-binding
      properties of MyBPC and to define MyBPC domain regions involved in actin
      interaction. Here, we have expressed full-length mouse cardiac MyBPC (cMyBPC) in
      a baculovirus system and shown that purified cMyBPC binds actin filaments with an
      affinity of 4.3 +/- 1.1 MUM and a 1:1 molar ratio with regard to an actin
      protomer. The actin binding by cMyBPC is independent of protein phosphorylation
      status and is not significantly affected by the presence of tropomyosin and
      troponin on the actin filament. In addition, cMyBPC-actin interaction is not
      modulated by calmodulin. To determine the region of cMyBPC that is responsible
      for its interaction with actin, we have expressed and characterized five
      recombinant proteins encoding fragments of the cMyBPC sequence. Recombinant N
      terminal fragments such as C0-C1, C0-C4, and C0-C5 cosediment with actin in a
      linear, nonsaturable manner. At the same time, MyBPC fragments lacking either the
      C0-C1 or C0-C4 region bind F-actin with essentially the same properties as full
      length protein. Together, our results indicate that cMyBPC interacts with actin
      via a single, moderate affinity site localized to the C-terminal region of the
      protein. In contrast, certain basic regions of the N-terminal domains of MyBPC
      may act as small polycations and therefore bind actin via nonspecific
      electrostatic interactions.

PMID- 21071445
TI  - Autophosphorylation activates Dictyostelium myosin II heavy chain kinase A by
      providing a ligand for an allosteric binding site in the alpha-kinase domain.
AB  - Dictyostelium discoideum myosin II heavy chain kinase A (MHCK A), a member of the
      atypical alpha-kinase family, phosphorylates sites in the myosin II tail that
      block filament assembly. Here we show that the catalytic activity of A-CAT, the
      alpha-kinase domain of MHCK A (residues 552-841), is severely inhibited by the
      removal of a disordered C-terminal tail sequence (C-tail; residues 806-841). The
      key residue in the C-tail was identified as Thr(825), which was found to be
      constitutively autophosphorylated. Dephosphorylation of Thr(825) using shrimp
      alkaline phosphatase decreased A-CAT activity. The activity of a truncated A-CAT
      lacking Thr(825) could be rescued by P(i), phosphothreonine, and a phosphorylated
      peptide, but not by threonine, glutamic acid, aspartic acid, or an
      unphosphorylated peptide. These results focused attention on a P(i)-binding
      pocket located in the C-terminal lobe of A-CAT. Mutational analysis demonstrated
      that the P(i)-pocket was essential for A-CAT activity. Based on these results, it
      is proposed that autophosphorylation of Thr(825) activates ACAT by providing a
      covalently tethered ligand for the P(i)-pocket. Ab initio modeling studies using
      the Rosetta FloppyTail and FlexPepDock protocols showed that it is feasible for
      the phosphorylated Thr(825) to dock intramolecularly into the P(i)-pocket.
      Allosteric activation is predicted to involve a conformational change in
      Arg(734), which bridges the bound P(i) to Asp(762) in a key active site loop.
      Sequence alignments indicate that a comparable regulatory mechanism is likely to
      be conserved in Dictyostelium MHCK B-D and metazoan eukaryotic elongation factor
      2 kinases.

PMID- 21071446
TI  - Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged
      neurons and antioxidant enzyme heme oxygenase-1 expression.
AB  - Glutamate-induced excito-neurotoxicity likely contributes to non-cell autonomous
      neuronal death in neurodegenerative diseases. Microglial clearance of dying
      neurons and associated debris is essential to maintain healthy neural networks in
      the central nervous system. In fact, the functions of microglia are regulated by
      various signaling molecules that are produced as neurons degenerate. Here, we
      show that the soluble CX3C chemokine fractalkine (sFKN), which is secreted from
      neurons that have been damaged by glutamate, promotes microglial phagocytosis of
      neuronal debris through release of milk fat globule-EGF factor 8, a mediator of
      apoptotic cell clearance. In addition, sFKN induces the expression of the
      antioxidant enzyme heme oxygenase-1 (HO-1) in microglia in the absence of
      neurotoxic molecule production, including NO, TNF, and glutamate. sFKN treatment
      of primary neuron-microglia co-cultures significantly attenuated glutamate
      induced neuronal cell death. Using several specific MAPK inhibitors, we found
      that sFKN-induced heme oxygenase-1 expression was primarily mediated by
      activation of JNK and nuclear factor erythroid 2-related factor 2. These results
      suggest that sFKN secreted from glutamate-damaged neurons provides both
      phagocytotic and neuroprotective signals.

PMID- 21071447
TI  - Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary
      chemopreventive agent curcumin.
AB  - The efficacy of the diphenol curcumin as a cancer chemopreventive agent is
      limited by its chemical and metabolic instability. Non-enzymatic degradation has
      been described to yield vanillin, ferulic acid, and feruloylmethane through
      cleavage of the heptadienone chain connecting the phenolic rings. Here we provide
      evidence for an alternative mechanism, resulting in autoxidative cyclization of
      the heptadienone moiety as a major pathway of degradation. Autoxidative
      transformation of curcumin was pH-dependent with the highest rate at pH 8 (2.2
      MUM/min) and associated with stoichiometric uptake of O(2). Oxidation was also
      catalyzed by recombinant cyclooxygenase-2 (COX-2) (50 nm; 7.5 MUM/min), and the
      rate was increased ~10-fold by the addition of 300 MUM H(2)O(2). The COX-2
      catalyzed transformation was inhibited by acetaminophen but not indomethacin,
      suggesting catalysis occurred by the peroxidase activity. We propose a mechanism
      of enzymatic or autoxidative hydrogen abstraction from a phenolic hydroxyl to
      give a quinone methide and a delocalized radical in the heptadienone chain that
      undergoes 5-exo cyclization and oxygenation. Hydration of the quinone methide
      (measured by the incorporation of O-18 from H(2)(18)O) and rearrangement under
      loss of water gives the final dioxygenated bicyclopentadione product. When
      curcumin was added to RAW264.7 cells, the bicyclopentadione was increased 1.8
      fold in cells activated by LPS; vanillin and other putative cleavage products
      were negligible. Oxidation to a reactive quinone methide is the mechanistic basis
      of many phenolic anti-cancer drugs. It is possible, therefore, that oxidative
      transformation of curcumin, a prominent but previously unrecognized reaction,
      contributes to its cancer chemopreventive activity.

PMID- 21071448
TI  - Deciphering the roles of outer membrane protein A extracellular loops in the
      pathogenesis of Escherichia coli K1 meningitis.
AB  - Outer membrane protein A (OmpA) has been implicated as an important virulence
      factor in several gram-negative bacterial infections such as Escherichia coli K1,
      a leading cause of neonatal meningitis associated with significant mortality and
      morbidity. In this study, we generated E. coli K1 mutants that express OmpA in
      which three or four amino acids from various extracellular loops were changed to
      alanines, and we examined their ability to survive in several immune cells. We
      observed that loop regions 1 and 2 play an important role in the survival of E.
      coli K1 inside neutrophils and dendritic cells, and loop regions 1 and 3 are
      needed for survival in macrophages. Concomitantly, E. coli K1 mutants expressing
      loop 1 and 2 mutations were unable to cause meningitis in a newborn mouse model.
      Of note, mutations in loop 4 of OmpA enhance the severity of the pathogenesis by
      allowing the pathogen to survive better in circulation and to produce high
      bacteremia levels. These results demonstrate, for the first time, the roles
      played by different regions of extracellular loops of OmpA of E. coli K1 in the
      pathogenesis of meningitis and may help in designing effective preventive
      strategies against this deadly disease.

PMID- 21071449
TI  - Desmosome assembly and cell-cell adhesion are membrane raft-dependent processes.
AB  - The aim of our study was to investigate the association of desmosomal proteins
      with cholesterol-enriched membrane domains, commonly called membrane rafts, and
      the influence of cholesterol on desmosome assembly in epithelial Madin-Darby
      canine kidney cells (clone MDc-2). Biochemical analysis proved an association of
      desmosomal cadherin desmocollin 2 (Dsc2) in cholesterol-enriched fractions that
      contain membrane raft markers caveolin-1 and flotillin-1 and the novel raft
      marker ostreolysin. Cold detergent extraction of biotinylated plasma membranes
      revealed that ~60% of Dsc2 associates with membrane rafts while the remainder is
      present in nonraft and cholesterol-poor membranes. The results of
      immunofluorescence microscopy confirmed colocalization of Dsc2 and ostreolysin.
      Partial depletion of cholesterol with methyl-beta-cyclodextrin disturbs desmosome
      assembly, as revealed by sequential recordings of live cells. Moreover,
      cholesterol depletion significantly reduces the strength of cell-cell junctions
      and partially releases Dsc2 from membrane rafts. Our data indicate that a pool of
      Dsc2 is associated with membrane rafts, particularly with the ostreolysin type of
      membrane raft, and that intact membrane rafts are necessary for desmosome
      assembly. Taken together, these data suggest cholesterol as a potential regulator
      that promotes desmosome assembly.

PMID- 21071450
TI  - Vascular endothelial growth factor A (VEGF-A) induces endothelial and cancer cell
      migration through direct binding to integrin {alpha}9{beta}1: identification of a
      specific {alpha}9{beta}1 binding site.
AB  - Integrin alpha9beta1 mediates accelerated cell adhesion and migration through
      interactions with a number of diverse extracellular ligands. We have shown
      previously that it directly binds the vascular endothelial growth factors (VEGF)
      A, C, and D and contributes to VEGF-induced angiogenesis and lymphangiogenesis.
      Until now, the alpha9beta1 binding site in VEGF has not been identified. Here, we
      report that the three-amino acid sequence, EYP, encoded by exon 3 of VEGF-A is
      essential for binding of VEGF to integrin alpha9beta1 and induces adhesion and
      migration of endothelial and cancer cells. EYP is specific for alpha9beta1
      binding and neither requires nor activates VEGFR-2, the cognate receptor for VEGF
      A. Following binding to EYP, integrin alpha9beta1 transduces cell migration
      through direct activation of the integrin signaling intermediates Src and focal
      adhesion kinase. This interaction is biologically important because it mediates
      in vitro endothelial cell tube formation, wound healing, and cancer cell
      invasion. These novel findings identify EYP as a potential site for directed
      pharmacotherapy.

PMID- 21071451
TI  - Lysyl oxidase-like-2 (LOXL2) is a major isoform in chondrocytes and is critically
      required for differentiation.
AB  - The lysyl oxidase family is made up of five members: lysyl oxidase (LOX) and
      lysyl oxidase-like 1-4 (LOXL1-LOXL4). All members share conserved C-terminal
      catalytic domains that provide for lysyl oxidase or lysyl oxidase-like enzyme
      activity; and more divergent propeptide regions. LOX family enzyme activities
      catalyze the final enzymatic conversion required for the formation of normal
      biosynthetic collagen and elastin cross-links. The importance of lysyl oxidase
      enzyme activity to normal bone development has long been appreciated, but
      regulation and roles for specific LOX isoforms in bone formation in vivo is
      largely unexplored. Fracture healing recapitulates aspects of endochondral bone
      development. The present study first investigated the expression of all LOX
      isoforms in fracture healing. A remarkable coincidence of LOXL2 expression with
      the chondrogenic phase of fracture healing was found, prompting more detailed
      analyses of LOXL2 expression in normal growth plates, and LOXL2 expression and
      function in developing ATDC5 chondrogenic cells. Data show that LOXL2 is
      expressed by pre-hypertrophic and hypertrophic chondrocytes in vivo, and that
      LOXL2 expression is regulated in vitro as a function of chondrocyte
      differentiation. Moreover, LOXL2 knockdown studies in vitro show that LOXL2
      expression is required for ATDC5 chondrocyte cell line differentiation through
      regulation of SNAIL and SOX9, important transcription factors that control
      chondrocyte differentiation. Taken together, data provide evidence that LOXL2,
      like LOX, is a multifunctional protein. LOXL2 promotes chondrocyte
      differentiation by mechanisms that are likely to include roles as both a
      regulator and an effector of chondrocyte differentiation.

PMID- 21071452
TI  - Location of glycine mutations within a bacterial collagen protein affects degree
      of disruption of triple-helix folding and conformation.
AB  - The hereditary bone disorder osteogenesis imperfecta is often caused by missense
      mutations in type I collagen that change one Gly residue to a larger residue and
      that break the typical (Gly-Xaa-Yaa)(n) sequence pattern. Site-directed
      mutagenesis in a recombinant bacterial collagen system was used to explore the
      effects of the Gly mutation position and of the identity of the residue replacing
      Gly in a homogeneous collagen molecular population. Homotrimeric bacterial
      collagen proteins with a Gly-to-Arg or Gly-to-Ser replacement formed stable
      triple-helix molecules with a reproducible 2  degrees C decrease in stability.
      All Gly replacements led to a significant delay in triple-helix folding, but a
      more dramatic delay was observed when the mutation was located near the N
      terminus of the triple-helix domain. This highly disruptive mutation, close to
      the globular N-terminal trimerization domain where folding is initiated, is
      likely to interfere with triple-helix nucleation. A positional effect of
      mutations was also suggested by trypsin sensitivity for a Gly-to-Arg replacement
      close to the triple-helix N terminus but not for the same replacement near the
      center of the molecule. The significant impact of the location of a mutation on
      triple-helix folding and conformation could relate to the severe consequences of
      mutations located near the C terminus of type I and type III collagens, where
      trimerization occurs and triple-helix folding is initiated.

PMID- 21071453
TI  - Incidence of ischaemic stroke according to income level among older people: the
      3C study.
AB  - BACKGROUND: stroke has been shown to follow a social gradient with incidence
      rising as socioeconomic status decreases. OBJECTIVE: to examine the relationship
      between socioeconomic status and ischaemic stroke risk amongst older people.
      SETTING: the Cities of Bordeaux, Dijon and Montpellier in France. SUBJECTS AND
      METHODS: nine thousand and two hundred and ninety-four non-institutionalised
      persons aged 65 years or more followed for 6 years. RESULTS: the distribution of
      cardiovascular risks factors was consistent with the classical finding of more
      favourable risk profiles among the advantaged socioeconomic groups. One hundred
      and thirty-six individuals developed a first ever ischaemic stroke (incidence
      rate: 3.2 per 1,000 py (person-years), 95% CI 2.7-3.8). The age- and sex-adjusted
      incidence of ischaemic stroke increased with increasing level of income (from 2.4
      to 4.1 per 1,000 py, P = 0.04). In the multivariable analysis adjusting for
      cardiovascular risk factors, the higher income group displayed a 80% increased
      risk of ischaemic stroke compared with less wealthy participants (hazards ratio
      1.77, 95% CI 1.20-2.61). CONCLUSIONS: in this community-based sample of older
      individuals, a higher level of household income was associated with a higher risk
      of ischaemic stroke, a reversal of the social gradient usually reported in
      younger age groups. Selective survival is one of the potential explanations for
      this unexpected finding.

PMID- 21071454
TI  - Human stem cell therapy in ischaemic stroke: a review.
AB  - Stroke is a leading cause of death and disability. Globally, 15 million people
      suffer a stroke each year, of whom more than 5 million die, and a further 5
      million are left permanently disabled. Current treatment options offer modest
      benefits, and there is a pressing need for new and effective treatments. Stem
      cell therapy is a well-established treatment modality for various haematological
      diseases, with its use now being explored in different disease processes,
      including various neurological diseases, as well as vascular conditions such as
      ischaemic heart disease and peripheral vascular disease. Promising results have
      been seen in animal models of stroke, with evidence of significant functional
      benefits. Translation to the bedside, however, is in its early stages. This
      review will discuss the scientific background to stem cell therapy in ischaemic
      stroke, including evidence from current clinical trials.

PMID- 21071455
TI  - Exploring the contributory factors for un-witnessed in-patient falls from the
      National Reporting and Learning System database.

PMID- 21071456
TI  - Postural sway velocity predicts osteoporotic fracture in community-dwelling
      elderly Japanese women: the Muramatsu Study.

PMID- 21071457
TI  - A 'health broker' role as a catalyst of change to promote health: an experiment
      in deprived Dutch neighbourhoods.
AB  - Urban social entrepreneurs have been suggested to play an essential part in the
      success of local health promotion initiatives. Up to now, roles like these have
      only been identified in retrospect. This prospective collaborative study explored
      the possibilities of institutionalizing a comparable role for a 'health broker'
      in four Dutch municipalities as an additional investment to promote health in
      deprived neighbourhoods. The theoretical notions of public and policy
      entrepreneurs as well as of boundary spanners were adopted as a reference
      framework. Documents produced by the collaborative project served as input for a
      qualitative analysis of the developments. We succeeded in implementing a 'health
      broker' role comparable to that of a bureaucratic public entrepreneur holding a
      formal non-leadership position. The role was empowered by sharing it among
      multiple professionals. Although positioned within one sector, the occupants of
      the new role felt more entitled to cross sectoral borders and to connect to local
      residents, compared to other within-sector functions. The 'health broker' role
      had the potential to operate as an 'anchoring point' for the municipal health
      sector (policy), public health services (practice) and/or the local residents
      (public). It was also possible to specify potential 'broking points', i.e.
      opportunities for health promotion agenda setting and opportunities to improve
      cross-sectoral collaboration, citizen participation and political and
      administrative support for health promotion efforts. The 'health broker' role we
      developed and implemented reflects the notion of systematic rather than
      individual entrepreneurship. Such a collective entrepreneurship may create
      additional opportunities to gradually strengthen local health promotion efforts.

PMID- 21071458
TI  - Evaluation of community-based interventions for non-communicable diseases:
      experiences from India and Indonesia.
AB  - This paper reports the results of formative and outcome evaluation of two ongoing
      community-based intervention programmes for integrated non-communicable disease
      (NCD) prevention and control in urban low-income settings of Ballabgarh near New
      Delhi, India, and in Depok, West Java Province of Indonesia. At both sites, a
      coalition of community members facilitated by academic institution and the World
      Health Organization, planned and implemented the intervention since 2004. The
      intervention consisted of advocacy and mediation with stakeholders, training of
      volunteers and school teachers, communication campaigns, risk assessment camps
      and reorientation of health services. The formative evaluation was based on the
      review of documents, and outcomes were assessed using the standardized surveys
      for NCD risk factors in 2003-2004 and 2006-2007. The baseline surveys showed that
      tobacco use, low intake of fruits and vegetable, suboptimal levels of physical
      activity and obesity were prevalent in both the communities. A frequent change in
      local administrators and lack of perceived priority for health and NCDs limited
      their involvement. Pre-existing engagement of community-based organizations and
      volunteers in health activities facilitated its implementation. The reach of the
      programme among the population was modest (25-32%). Health system interventions
      resulted in increased diagnosis and better management of NCDs at health
      facilities. Early outcome measures showed mixed results of change in different
      risk factors. The experiences gained are being used in both countries to expand
      and provide technical support to national efforts. This paper adds to the
      knowledge base on the feasibility of designing and implementing large-scale
      community-based interventions for integrated prevention of NCDs through
      modification of risk factors.

PMID- 21071459
TI  - Effects of low incubation temperatures on the bactericidal activity of anti
      tuberculosis drugs.
AB  - OBJECTIVES: to explore the effect of low incubation temperatures and the
      consequent slowing of bacterial metabolism on the bactericidal action of anti
      tuberculosis drugs against Mycobacterium tuberculosis. METHODS: counting of
      surviving bacteria during exposure of static cultures to 1 mg/L isoniazid, 2 mg/L
      rifampicin, 0.5 or 2 mg/L TMC207 and 40 or 160 mg/L pyrazinamide, usually for
      periods of 21 days at temperatures of 37, 25, 22, 19, 16 or 8 degrees C. RESULTS:
      the bactericidal activities of isoniazid and rifampicin were progressively
      reduced at 25 and 22 degrees C, and were minimal at lower temperatures. TMC207
      was immediately bactericidal at 37 degrees C, in contrast to the early static
      phase reported with log phase cultures, and showed less change in activity as
      incubation temperatures were reduced than did rifampicin or isoniazid.
      Pyrazinamide was more bactericidal when incubation temperatures were reduced
      below 37 degrees C and when the static seed cultures were most dormant.
      CONCLUSIONS: these results can be explained by the surmise that at low
      temperatures bacterial energy is at a low level with only just sufficient ATP to
      maintain homeostasis, making the bacteria more susceptible to the blocking of ATP
      synthesis by TMC207. Insufficient ATP at low temperature would also hinder the
      export of pyrazinoic acid, the toxic product of the pro-drug pyrazinamide, from
      the mycobacterial cell by an inefficient efflux pump that requires energy.

PMID- 21071460
TI  - Staphylococcal bovine mastitis in France: enterotoxins, resistance and the human
      Geraldine methicillin-resistant Staphylococcus aureus clone.

PMID- 21071462
TI  - Exposure to magnetic fields of railway engine drivers: a case study in Italy.
AB  - A case study of exposure assessment of railway workers to static and extremely
      low frequency (ELF) magnetic fields is presented. A measurement campaign was
      conducted in aboard Italian main line trains. All measurements were performed on
      board during regular service (two engine drivers were simultaneously present), in
      all places potentially accessible to personnel, considering routes ranging from a
      few tens of kilometres to hundreds of kilometres. The measurement protocol was
      mostly based on broadband metres and personal metres were employed to assess
      individual exposure. Surveys on static and ELF magnetic fields were performed for
      seven different models of engine or electrified train. Traction motors were fed
      by alternating current (AC) current, except for two engines, where AC current fed
      only auxiliary services. The final result is that the average exposure to static
      magnetic field was a little higher than the background geomagnetic field;
      occasionally in few areas it could reach levels of the order of millitesla. The
      average exposure to ELF magnetic fields was in the order of 1-2 MUT, with higher
      levels (few microtesla) only for one engine; occasionally in hot spots, close to
      wiring or specific equipment, the field values could reach several tens of
      microtesla.

PMID- 21071463
TI  - Theoretical assessment of whole body counting performances using numerical
      phantoms of different gender and sizes.
AB  - A goal of whole body counting (WBC) is the estimation of the total body burden of
      radionuclides disregarding the actual position within the body. To achieve the
      goal, the detectors need to be placed in regions where the photon flux is as
      independent as possible from the distribution of the source. At the same time,
      the detectors need high photon fluxes in order to achieve better efficiency and
      lower minimum detectable activities. This work presents a method able to define
      the layout of new WBC systems and to study the behaviour of existing ones using
      both detection efficiency and its dependence on the position of the source within
      the body of computational phantoms.

PMID- 21071464
TI  - PACAP-mediated sperm-cumulus cell interaction promotes fertilization.
AB  - The developing acrosome in spermatids contains pituitary adenylate cyclase
      activating polypeptide (PACAP). However, the role of the acrosomal PACAP remains
      unclear because it has not been detected in mature spermatids and sperm. We
      reinvestigated whether the sperm acrosome contains PACAP. An antiserum produced
      against PACAP reacted to the anterior acrosome in epididymal sperm fixed under
      mild conditions, suggesting that PACAP acts on oocytes and/or cumulus cells at
      the site of fertilization. Immunolabeling and RT-PCR demonstrated the presence of
      PACAP type I receptor, a PACAP-specific receptor, in postovulatory cumulus cells.
      To investigate the role of PACAP in fertilization, we pretreated cumulus-oocyte
      complexes with the polypeptide. At a low concentration of sperm, the
      fertilization rate was significantly enhanced by PACAP in a dose-dependent
      manner. Sperm penetration through the oocyte investment, cumulus layer, and zona
      pellucida was also enhanced by PACAP. The enhancement was probably due to an
      enhancement in sperm motility and the zona-induced acrosome reaction, which were
      stimulated by a cumulus cell-releasing factor. Indeed, PACAP treatment increased
      the secretion of progesterone from the cumulus-oocyte complexes. These results
      strongly suggest that in response to PACAP, cumulus cells release a soluble
      factor that probably stimulates sperm motility and the acrosome reaction, thereby
      promoting fertilization.

PMID- 21071465
TI  - Predictive factors for multiple sclerosis in patients with clinically isolated
      spinal cord syndrome.
AB  - OBJECTIVES: To identify predictors of conversion to definite multiple sclerosis
      (MS) in patients with a cord clinically isolated syndrome. METHODS: The
      predictive values for conversion to MS of clinical, magnetic resonance imaging
      (MRI) and cerebrospinal fluid (CSF) variables in 114 patients with acute partial
      myelitis confirmed by a spinal cord lesion on MRI were studied. Other causes of
      cord syndromes were excluded. RESULTS: MS was diagnosed in 78 patients (86%)
      during 4.0 +/- 1.9 years of follow-up. Some 67 of these patients had a second
      clinical episode. The diagnosis of isolated myelitis was maintained for 36
      patients, 78% of whom (28 cases) were followed for at least 2 years, comparable
      to the MS patients. Age, bladder involvement, >= 2 cord lesions on MRI, >= 9
      brain lesions, >= 3 periventricular lesions and intrathecal IgG synthesis
      predicted conversion to clinically definite MS. Multivariate logistic analysis
      identified three predictors of MS diagnosis: age <= 40 years, inflammatory CSF
      and >= 3 periventricular lesions on brain MRI. CONCLUSION: Two out of three
      baseline factors (age, periventricular lesions and inflammatory CSF) predicted
      conversion to MS with better accuracy than the revised McDonald criteria for
      dissemination in space.

PMID- 21071466
TI  - Increasing frequency of multiple sclerosis in Catania, Sicily: a 30-year survey.
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to determine the
      prevalence and incidence of multiple sclerosis (MS) and its temporal profiles
      from 1975 to 2005 in the city of Catania. METHODS: The incidence of MS from 1975
      to 31 December 1999 had been previously investigated by the same group. The
      frequency of MS in the community of Catania from 1 January 2000 to 31 December
      2004 was studied in a population of 313,110 inhabitants (2001 census). All
      patients who satisfied Poser's criteria were considered as prevalent and incident
      cases. RESULTS: Three hundred and ninety-eight patients with MS who had
      experienced the clinical onset of the disease before 31 December 2004 were found
      in a population of 313,110 inhabitants. The prevalence rate was 127.1/100,000
      [95% confidence interval (CI) 115.1-140.4]. From 2000 to 2004, 108 patients with
      MS had clinical onset of the disease. The mean annual incidence was 7.0/100,000
      (95% CI 5.7-13.7) and was higher in women (8.4/100,000; 95% CI 6.4-10.5) than in
      men (5.3/100,000; 95% CI 3.7-7.2). The mean length of time between the date of
      clinical onset and the date of the diagnosis was 1.4 +/- 1.7 years. During the
      last 30 years the incidence of MS in this population increased from 1.3/100,000
      during the first quinquennium (1975-9) to 7.0/100,000 during 2000-4. CONCLUSIONS:
      Incidence rates have further increased in this population, suggesting that the
      risk of MS is still increasing.

PMID- 21071467
TI  - AZD1152 negatively affects the growth of anaplastic thyroid carcinoma cells and
      enhances the effects of oncolytic virus dl922-947.
AB  - Novel therapeutic approaches are required for the treatment of anaplastic thyroid
      carcinoma (ATC), an incurable disease resistant to current available therapies.
      Aurora B is an important mitotic kinase involved in chromosome segregation and
      cytokinesis. It is overexpressed in many cancers including ATC and represents a
      potential target for chemotherapy. The effects of AZD1152, a specific Aurora B
      kinase inhibitor, have been evaluated against ATC, showing G(2)/M accumulation,
      polyploidy and subsequent cell death by mitotic catastrophe upon drug treatment.
      Only three administrations of AZD1152 significantly reduced the growth of ATC
      tumour xenogratfs. Oncolytic viruses in association with other forms of treatment
      have proven highly promising in preclinical and clinical reports. The oncolytic
      adenovirus dl922-947 is active against ATC cells, and we have evaluated the
      effects of the association between AZD1152 and dl922-947. In cells treated with
      virus and drug, we report additive/synergistic killing effects. Interestingly,
      the phosphorylation of histone H3 (Ser10), the main Aurora B substrate, is
      inhibited by dl922-947 in a dose-dependent manner, and completely abolished in
      association with AZD1152. The combined treatment significantly inhibited the
      growth of ATC tumour xenografts with respect to single treatments. Our data
      demonstrate that the Aurora B inhibitor AZD1152, alone or in combination with
      oncolytic virus dl922-947, could represent a novel therapeutic option for the
      treatment of ATC.

PMID- 21071468
TI  - Serum vitamin D levels and exercise-induced bronchoconstriction in children with
      asthma.
AB  - Epidemiological studies have established a relationship between low levels of
      serum vitamin D and reduced lung function in healthy adults, and asthma onset and
      severity in children. However, no study has examined the relationship between
      vitamin D levels and exercise-induced bronchoconstriction in asthmatic children.
      We evaluated the relationship between 25-hydroxyvitamin D concentrations and
      baseline forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and
      change in FEV1 (DeltaFEV1) after a standardised exercise challenge in 45 children
      with intermittent asthma. Only 11% of the children had desirable serum vitamin D
      levels (at least 30-40 ng.mL(-1)). A positive correlation was found between serum
      25-hydroxyvitamin D and both FVC (r=0.34; p=0.037) and FEV1 (r=0.32; p=0.037).
      Subjects with a positive response to the exercise challenge (DeltaFEV1>=10%)
      presented lower serum levels of 25-hydroxyvitamin D than children with a negative
      challenge (mean+/-sd 16.2+/-5.2 versus 23.4+/-7.0 ng.mL(-1), respectively;
      p=0.001). Our results indicate that hypovitaminosis D is frequent in asthmatic
      children who live in a Mediterranean country. In those children, lower levels of
      vitamin D are associated with reduced lung function and increased reactivity to
      exercise.

PMID- 21071469
TI  - Ageing and COPD affect different domains of nutritional status: the ECCE study.
AB  - Chronic obstructive pulmonary disease (COPD) and ageing may contribute to
      malnutrition. We aimed to explore whether COPD and ageing determine malnutrition
      in different manners. 460 stable COPD outpatients (376 males and 84 females) from
      the Extrapulmonary Consequences of COPD in the Elderly (ECCE) study database were
      investigated (age 75.0+/-5.9 yrs; forced expiratory volume in 1 s 54.7+/-18.3%
      predicted). Nutritional status was evaluated using the Mini Nutritional
      Assessment(r) (MNA) questionnaire. From the MNA, three scores exploring the
      domains of the nutritional status were calculated: body composition, energy
      intake and body functionality scores. Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) stages were negatively correlated with five MNA items
      exploring mobility, patient's perception of own nutrition and health status, and
      arm and calf circumferences (lowest Spearman's rho (rs)=-0.011; highest p=0.039).
      GOLD stages were independently correlated with body composition and body
      functionality scores (model r2=0.073). Age was negatively correlated with four
      MNA items exploring loss of appetite, fluid intake, mobility and autonomy in
      daily life (lowest rs=-0.013; highest p=0.030). Age was independently correlated
      with body functionality score (model r2=0.037). Severe COPD and ageing are
      independent and probably concurrent conditions leading to malnutrition. The MNA
      questionnaire allows a valuable insight into the complexity of components of
      nutritional status and may provide useful clues for treatment strategies.

PMID- 21071470
TI  - Inhaled corticosteroids and lower lung function decline in young children with
      cystic fibrosis.
AB  - A recent American registry analysis in cystic fibrosis (CF) children showed less
      lung function decline after starting inhaled corticosteroid (ICS) use. We
      therefore examined the influence of ICS treatment on lung function in Belgian CF
      patients. Data from patients >= 6 yrs of age were eligible, provided entries on
      lung function, height and ICS use were available in two consecutive years. Data
      after oral steroid use or transplant were excluded. 852 subjects contributed data
      with 2,976 data pairs analysed, 44.9% concerning years of ICS use. Yearly %
      predicted decline in forced expiratory volume in 1 s (FEV1) was 1.07% lower
      during ICS use (p = 0.001). Subgroup analysis for age revealed that the lower
      FEV1 decline rate during ICS use was only statistically significant in children 6
      12 yrs of age (2.56%; p = 0.0003). Baseline FEV(1) was lower by 5.89% (p <
      0.0001) in ICS users for all age groups combined, but there was no difference in
      baseline lung function in the children 6-12 yrs of age. In 6-12-yr-old children
      with CF, baseline lung function was similar in ICS users and nonusers, but
      annualised FEV1 decline was 2.56% pred lower in ICS users. Our data therefore
      support recent American findings.

PMID- 21071471
TI  - The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in
      microscopic polyangiitis.
AB  - Lung fibrosis is considered a severe manifestation of microscopic polyangiitis
      (MPA). Antimyeloperoxidase (anti-MPO) antibodies in MPA patients' sera can
      activate MPO and lead to the production of reactive oxygen species (ROS). While
      high levels of ROS are cytotoxic, low levels can induce fibroblast proliferation.
      Therefore, we hypothesised that the oxidative stress induced by anti-MPO
      antibodies could contribute to lung fibrosis. 24 MPA patients (45 sera) were
      enrolled in the study, including nine patients (22 sera) with lung fibrosis.
      Serum advanced oxidation protein products (AOPP), MPO-induced hypochlorous acid
      (HOCl) and serum-induced fibroblast proliferation were assayed. AOPP levels, MPO
      induced HOCl production and serum-induced fibroblast proliferation were higher in
      patients than in healthy controls (p<0.0001, p=0.0001 and p=0.0005,
      respectively). Increased HOCl production was associated with active disease
      (p=0.002). Serum AOPP levels and serum-induced fibroblast proliferation were
      higher in patients with active MPA and lung fibrosis (p<0.0001). A significant
      linear relationship between fibroblast proliferation, AOPP levels and HOCl
      production was observed only in patients with lung fibrosis. Oxidative stress, in
      particular the production of HOCl through the interaction of MPO with anti-MPO
      antibodies, could trigger the fibrotic process observed in MPA.

PMID- 21071473
TI  - Inflammatory responses predict long-term mortality risk in community-acquired
      pneumonia.
AB  - Long-term outcomes in patients surviving community-acquired pneumonia (CAP) are
      still incompletely understood. This study investigates the association of
      clinical parameters and blood markers with long-term mortality. We prospectively
      followed 877 CAP patients from a previous multicentre trial for 18 months follow
      up and investigated all-cause mortality following hospital discharge. Overall
      mortality was 17.3% (95% CI 14.8-19.8%) with a 12.8% (95% CI 10.9-15.0%)
      mortality incidence rate per year. Initial risk assignment using the Pneumonia
      Severity Index was accurate during the 18 month follow-up. Multivariable
      regression models (hazard ratio, 95% CI) designated the following as independent
      risk factors for long-term mortality: male sex (1.7, 1.2-2.5); chronic
      obstructive pulmonary disease (1.5, 1.1-2.1); neoplastic disease (2.5, 1.7-3.7);
      and highest quartile of peak pro-adrenomedullin level (3.3, 1.7-6.2). Initial
      presentation with temperature>38.7 degrees C (0.4, 0.2-0.6), chills (0.6, 0.4
      0.99) and highest quartile of the inflammatory marker C-reactive-protein (0.3,
      0.2-0.5) were independent protective factors. A weighted risk score based on
      these variables showed good discrimination (area under receiver operating
      characteristic curve 0.78, 95% CI 0.74-0.82). Pronounced clinical and laboratory
      signs of systemic inflammatory host response upon initial hospital stay were
      associated with favourable long-term prognosis. Further studies should address
      whether closer monitoring of high-risk CAP patients after hospital discharge
      favourably impacts long-term mortality.

PMID- 21071472
TI  - FTY720-induced human pulmonary endothelial barrier enhancement is mediated by c
      Abl.
AB  - Strategies to improve pulmonary endothelial barrier function are needed to
      reverse the devastating effects of vascular leak in acute respiratory distress
      syndrome. FTY720 is a pharmaceutical analogue of the potent barrier-enhancing
      phospholipid sphingosine 1-phosphate (S1P). FTY720 decreases vascular
      permeability by an incompletely characterised mechanism that differs from S1P.
      Here, we describe its barrier-promoting effects on intracellular signalling and
      junctional assembly formation in human pulmonary endothelium. Permeability of
      cultured human pulmonary endothelial cells was assessed using transendothelial
      electrical resistance and dextran transwell assays. Junctional complex formation
      was assessed using membrane fractionation and immunofluorescence. Pharmacological
      inhibitors and small interfering (si)RNA were utilised to determine the effects
      of individual components on permeability. Unlike S1P, FTY720 failed to induce
      membrane translocation of adherens junction or tight junction proteins. beta
      catenin, occludin, claudin-5 or zona occludens protein (ZO)-1/ZO-2 siRNAs did not
      alter FTY720-induced barrier enhancement. FTY720 induced focal adhesion kinase
      (FAK) phosphorylation and focal adhesion formation, with FAK siRNA partially
      attenuating the prolonged phase of barrier enhancement. Inhibition of Src,
      protein kinase (PK)A, PKG, PKC or protein phosphatase 2A failed to alter FTY720
      induced barrier enhancement. FTY720 increased c-Abl tyrosine kinase activity and
      c-Abl siRNA attenuated peak barrier enhancement after FTY720. FTY720 enhances
      endothelial barrier function by a novel pathway involving c-Abl signalling.

PMID- 21071474
TI  - Tuberculosis screening of migrants to low-burden nations: insights from
      evaluation of UK practice.
AB  - Tuberculosis (TB) primarily occurs in the foreign-born in European countries,
      such as the UK, where increasing notifications and the high proportion of foreign
      born cases has refocused attention on immigrant (new entrant) screening. We
      investigated how UK primary care organisations (PCOs) screen new entrants and
      whether this differs according to TB burden in the PCOs (incidence < 20 or >= 20
      cases per 100,000 per annum). An anonymous, 20-point questionnaire was sent to
      all 192 UK PCOs asking which new entrants are screened, who is screened for
      active TB/latent TB infection (LTBI) and the methods used. Descriptive analyses
      were undertaken. Categorical responses were compared using the Chi-squared test.
      177 (92.2%) out of 192 PCOs responded; all undertook screening action in response
      to abnormal chest radiographs, but only 107 (60.4%) screened new entrants for
      LTBI. Few new entrants had active TB diagnosed (median 0.0%, interquartile range
      (IQR) 0.0-0.5%) but more were identified with LTBI (median 7.85%, IQR 4.30
      13.50%). High-burden PCOs were significantly less likely to screen new entrants
      for LTBI (OR 0.26, 95% CI 0.12-0.54; p<0.0001). Among PCOs screening for LTBI,
      there was substantial deviation from national guidance in selection of new
      entrant subgroups and screening method. Considerable heterogeneity and deviation
      from national guidance exist throughout the UK new entrant screening process,
      with high-burden regions undertaking the least screening. Forming an accurate
      picture of current front-line practice will help to inform future development of
      European new entrant screening policy.

PMID- 21071475
TI  - Modulating progenitor accumulation attenuates lung angiogenesis in a mouse model
      of asthma.
AB  - Asthmatic responses are associated with the lung homing of bone marrow (BM)
      derived progenitors implicated as effectors of disease pathology. Studies have
      shown that increases in lung extracted vascular endothelial progenitor cells
      (VEPCs) correlate with airway angiogenesis and declining lung function. We
      investigated the effect of modulating lung homing of VEPCs on tissue remodelling
      and airway hyperresponsiveness (AHR). BALB/c mice were sensitised to ovalbumin,
      subjected to a chronic exposure protocol and given early concurrent or delayed
      treatment with a modulator of progenitor traffic, AMD3100 (CXC chemokine receptor
      4 antagonist; inhibits chemotactic activity of stromal-derived factor-1alpha on
      VEPCs). After ovalbumin challenge, early haemopoietic stem cells (HSCs) and VEPCs
      were enumerated along with indices of airway inflammation, lung morphometry and
      AHR. Following ovalbumin challenge, there was a decrease in BM and an associated
      increase in the lung tissue-extracted HSCs and VEPCs, together with increases in
      airway eosinophilia, microvessel density and AHR. These outcomes were
      significantly inhibited by early concurrent treatment with AMD3100. Where lung
      disease was established, delayed treatment with AMD3100 significantly attenuated
      HSC numbers and lung angiogenesis but only partially reversed sustained AHR
      compared with untreated ovalbumin-exposed mice. Progenitor lung homing is
      associated with the development of asthma pathology, and early modulation of this
      accumulation can prevent airway remodelling and lung dysfunction.

PMID- 21071476
TI  - Selective estrogen receptor modulators as brain therapeutic agents.
AB  - Selective estrogen receptor modulators (SERMs), used for the treatment of breast
      cancer, osteoporosis, and menopausal symptoms, affect the nervous system. Some
      SERMs trigger neuroprotective mechanisms and reduce neural damage in different
      experimental models of neural trauma, brain inflammation, neurodegenerative
      diseases, cognitive impairment, and affective disorders. New SERMs with specific
      actions on neurons and glial cells may represent promising therapeutic tools for
      the brain.

PMID- 21071477
TI  - Tumour necrosis factor antagonists and the risk of cardiovascular disease in
      patients with rheumatoid arthritis: a systematic literature review.
AB  - OBJECTIVES: RA is associated with early ischaemic heart disease. This appears to
      be driven largely by the presence of chronic inflammation. Studies suggest that
      treatment with disease-modifying drugs such as MTX may reduce the incidence of
      cardiovascular events in RA. Anti-TNF therapies significantly reduce inflammation
      in RA. However, the extent to which these agents also reduce cardiovascular
      disease (CVD) is uncertain. The purpose of this study was to explore the effect
      of anti-TNF agents on CVD in RA using a systematic literature review. METHODS: We
      searched for studies of adults with RA treated with TNF antagonists where
      cardiovascular outcomes were recorded using MEDLINE, EMBASE, Cochrane Database,
      Database of Abstracts and Reviews of Effects, Health Technology Appraisal,
      Science Citation Index and Clinical Evidence from 1989 to 2010. Conference
      proceedings for the British Society of Rheumatology, ACR and EULAR between 2005
      and 2009 were hand searched. Two reviewers assessed abstracts for inclusion and
      then quality of selected papers was assessed. RESULTS: A total of 1840 abstracts
      were identified and 20 articles were suitable for inclusion. Information was
      obtained on the effect of TNF antagonists on overall CVD events, myocardial
      infarction, strokes and heart failure. CONCLUSION: In many studies, TNF
      antagonists appear to reduce the likelihood of CVD in individuals with RA.
      Reassuringly, there does not appear to be an increased risk of cardiac failure.
      However, the reduction in CVD is not as consistently seen as with studies of MTX.

PMID- 21071478
TI  - 'If I didn't have RA I wouldn't give them house room': the relationship between
      RA, footwear and clothing choices.
AB  - OBJECTIVES: The aim of this study was to develop a greater understanding of the
      impact of RA on women's self-image and self-presentation via an exploration of
      their clothing choices. METHODS: Located within a qualitative symbolic
      interactionist approach, 15 women with RA (age range 38-74 years, disease
      duration 1-47 years) each participated in two interviews. The first explored the
      impact of RA on their feelings about their bodies and their appearance; the
      second explored the factors that informed their clothing choices and the way they
      presented themselves. All interviews were digitally recorded and transcribed
      verbatim, digital photographs of the women's clothes and shoes were taken. Data
      were analysed jointly by both authors using thematic network analysis. RESULTS:
      Shoes were identified as greatly influencing the women's clothing choices and how
      they presented themselves. Three themes were identified that explored the
      structural and symptomatic impact of RA on the women's feet, the strategies they
      had developed to resolve their footwear needs outside of prescription footwear
      and the significant impact that footwear had on their clothing choices and self
      presentation. Insights from these data highlight the polarity that exists between
      the clinical, functional attitudes towards shoes and their social status.
      CONCLUSION: While aesthetic issues challenge the acceptability of prescription
      footwear, problems also exist with the functionality and comfort of footwear
      available on high streets. A more collaborative approach to the design of
      footwear is required for both prescription and mainstream footwear to meet the
      needs of women with RA.

PMID- 21071480
TI  - Measurement properties of the osteoarthritis of knee and hip quality of life
      OAKHQOL questionnaire: an item response theory analysis.
AB  - OBJECTIVE: To further document the measurement properties of each domain of the
      OA of knee and hip quality of life (OAKHQOL) questionnaire by a Rasch analysis.
      METHODS: The OAKHQOL self-administered questionnaire has been developed to assess
      health-related quality of life in lower limb OA. Patients with various degrees of
      severity of knee or hip OA answered the questionnaire. For each domain, their
      responses to the items were analysed with a Rasch family model, the partial
      credit model. We examined the fit of data to model expectations, as well as
      assumptions of unidimensionality and local independence. Invariance was assessed
      by analysis of differential item functioning (DIF) by sex, age and joint.
      Analyses used the RUMM2020 software (Rumm Laboratory, Perth, Western Australia).
      RESULTS: Responses for 544 patients were analysed: 297 had medically managed OA
      and 247 were waiting for arthroplasty surgery. For the 40 items of the OAKHQOL,
      data analysis showed 5 with disordered thresholds and 9 with DIF (5 for joint, 3
      for sex and 1 for age). Ten pairs of items showed local dependence and four
      domains showed unidimensionality. Full-item domains and domains without the
      misfitted items did not differ in patient-estimates data; therefore any bias at
      the item level is negligible when considering the domain scores. CONCLUSION: The
      five domains of the OAKHQOL questionnaire show good measurement properties by
      Rasch analysis and provide valid scales.

PMID- 21071479
TI  - Ultrasound Doppler measurements predict success of treatment with anti-TNF
      &alpha; drug in patients with rheumatoid arthritis: a prospective cohort study.
AB  - OBJECTIVE: To investigate the predictive ability of core outcomes applied in RA
      trials, including ultrasound (US) Doppler (USD) measurements differentiating
      patients who remain on anti-TNF-alpha therapy following 1 year. METHODS: Patients
      with RA in anti-TNF-alpha therapy were followed 1 year after therapy initiation.
      All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a
      USD examination, clinical examination including tender and swollen joint count,
      visual analogue scale (VAS) global and HAQ, biochemical measures and 28-joint DAS
      (DAS28) were collected for all patients. The amount of USD signal in the synovium
      was quantified by measuring the percentage of colour pixels-the colour fraction
      (CF). Predictive validity for patients who remain on anti-TNF-alpha therapy after
      1 year was assessed for both USD measurements and other disease measures.
      Baseline values of disease measures of patients who remained on treatment after 1
      year was compared with those who stopped therapy. RESULTS: The study cohort
      consisted of 109 patients. In this study, the baseline CF was the only measure
      predicting which patients would stay on the initial anti-TNF-alpha therapy for 1
      year, evaluated using the square-root of CF (P = 0.024). The other disease
      markers could not significantly differentiate between the two groups of patients,
      with P-values of 0.86 and 0.98 for tender and swollen joint count, respectively,
      0.86 for CRP, 0.24 for VAS, 0.10 for HAQ and 0.38 for DAS28. CONCLUSION: There is
      now evidence to support that baseline USD, in contrast to clinical measures, can
      predict which patients will remain on anti-TNF-alpha 1 year after initiating
      therapy.

PMID- 21071481
TI  - Polymyalgia rheumatica is associated with extensor tendon tenosynovitis but not
      with synovitis of the hands: a magnetic resonance imaging study.
AB  - OBJECTIVES: To study with MRI the hands of consecutive PMR patients, who were not
      selected on the basis of peripheral arthritis, with a correlation to clinical and
      laboratory findings. METHODS: Twenty-six hands of 15 PMR patients and 26 hands of
      13 healthy controls were studied by extremity-dedicated MRI for the presence of
      synovitis, tenosynovitis, soft-tissue oedema, bone marrow oedema and erosions.
      RESULTS: Sixteen (61.6%) of the 26 PMR hands and 4 (15.4%) of the 26 control
      hands showed tenosynovitis (P = 0.001). Extensor tendon tenosynovitis was seen in
      9 (34.6%) of the 26 PMR hands, but in only 1 (3.8%) control hand (P = 0.002) and
      flexor tenosynovitis was seen in 12 (46.1%) of the 26 PMR hands and in 4 (15.4%)
      of the 26 control hands (P = 0.03). All other features were similar in the two
      groups. CONCLUSIONS: Our data support the view that tenosynovitis, especially of
      the extensor tendons, is a frequent event in PMR, unrelated to clinical
      involvement of the hand. This finding is in agreement with the concept of PMR as
      a disease of extra-articular structures.

PMID- 21071483
TI  - Re-offending rates are lower among offenders treated in secure hospitals than
      among mentally ill people held in prison.

PMID- 21071485
TI  - Suicide attempts in people taking isotretinoin for acne.

PMID- 21071484
TI  - Association of suicide attempts with acne and treatment with isotretinoin:
      retrospective Swedish cohort study.
AB  - OBJECTIVE: To assess the risk of attempted suicide before, during, and after
      treatment with isotretinoin for severe acne. DESIGN: Retrospective cohort study
      linking a named patient register of isotretinoin users (1980-9) to hospital
      discharge and cause of death registers (1980-2001). SETTING: Sweden, 1980-2001.
      Population 5756 patients aged 15 to 49 years prescribed isotretinoin for severe
      acne observed for 17 197 person years before, 2905 person years during, and 87
      120 person years after treatment. MAIN OUTCOME MEASURES: Standardised incidence
      ratio (observed number divided by expected number of suicide attempts
      standardised by sex, age, and calendar year), calculated up to three years
      before, during, and up to 15 years after end of treatment. RESULTS: 128 patients
      were admitted to hospital for attempted suicide. During the year before
      treatment, the standardised incidence ratio for attempted suicide was raised:
      1.57 (95% confidence interval 0.86 to 2.63) for all (including repeat) attempts
      and 1.36 (0.65 to 2.50) counting only first attempts. The standardised incidence
      ratio during and up to six months after treatment was 1.78 (1.04 to 2.85) for all
      attempts and 1.93 (1.08 to 3.18) for first attempts. Three years after treatment
      stopped, the observed number of attempts was close to the expected number and
      remained so during the 15 years of follow-up: standardised incidence ratio 1.04
      (0.74 to 1.43) for all attempts and 0.97 (0.64 to 1.40) for first attempts.
      Twelve (38%) of 32 patients who made their first suicide attempt before treatment
      made a new attempt or committed suicide thereafter. In contrast, 10 (71%) of the
      14 who made their first suicide attempt within six months after treatment stopped
      made a new attempt or committed suicide during follow-up (two sample test of
      proportions, P=0.034). The number needed to harm was 2300 new six month
      treatments per year for one additional first suicide attempt to occur and 5000
      per year for one additional repeat attempt. CONCLUSIONS: An increased risk of
      attempted suicide was apparent up to six months after the end of treatment with
      isotretinoin, which motivates a close monitoring of patients for suicidal
      behaviour for up to a year after treatment has ended. However, the risk of
      attempted suicide was already rising before treatment, so an additional risk due
      to the isotretinoin treatment cannot be established. As patients with a history
      of suicide attempts before treatment made new attempts to a lesser extent than
      did patients who started such behaviour in connection with treatment, patients
      with severe acne should not automatically have isotretinoin treatment withheld
      because of a history of attempted suicide.

PMID- 21071486
TI  - Tales from the bench: laboratory diagnosis of malaria.
AB  - This is a practical laboratory overview of current detection methods for malaria
      parasites, suitable for use in developing countries.

PMID- 21071487
TI  - Putting GPs in charge of NHS budget is an "extraordinary gamble".

PMID- 21071488
TI  - Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas
      by the Leksell gamma knife?
AB  - OBJECTIVE: Radiation therapy is one of the treatment options for pituitary
      adenomas. The most common side effect associated with Leksell gamma knife (LGK)
      irradiation is the development of hypopituitarism. The aim of this study was to
      verify that hypopituitarism does not develop if the maximum mean dose to
      pituitary is kept under 15 Gy and to evaluate the influence of maximum distal
      infundibulum dose on the development of hypopituitarism. DESIGN AND METHODS: We
      followed the incidence of hypopituitarism in 85 patients irradiated with LGK in
      1993-2003. The patients were divided in two subgroups: the first subgroup
      followed prospectively (45 patients), irradiated with a mean dose to pituitary
      <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively
      2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum
      TSH, free thyroxine, testosterone or 17beta-oestradiol, IGF1, prolactin and
      cortisol levels were evaluated before and every 6 months after LGK irradiation.
      RESULTS: Hypopituitarism after LGK irradiation developed only in 1 out of 45
      (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to
      72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation
      dose to the distal infundibulum was found as an independent factor of
      hypopituitarism with calculated maximum safe dose of 17 Gy. CONCLUSION: Keeping
      the mean radiation dose to pituitary under 15 Gy and the dose to the distal
      infundibulum under 17 Gy prevents the development of hypopituitarism following
      LGK irradiation.

PMID- 21071489
TI  - Female obesity adversely affects assisted reproductive technology (ART) pregnancy
      and live birth rates.
AB  - BACKGROUND: Obesity has risen among women in the USA, including those seeking
      infertility treatments. In 2007, height and weight were added to the Society for
      Assisted Reproductive Technology Clinic Online Reporting System (SART CORS),
      permitting calculation of BMI (weight/height(2)) for the first time using this
      national dataset. METHODS: The SART CORS was used to evaluate the odds of failure
      to achieve a clinical intrauterine pregnancy and failure to achieve a live birth
      by the woman's age, BMI and oocyte source (autologous versus donor), controlling
      for race and ethnicity, day of embryo transfer, number of embryos transferred and
      infertility diagnoses. The reference population was women with normal BMI.
      RESULTS: There were 45 163 ART embryo transfers where maternal height and weight
      were recorded. Increasing obesity was associated with a significant rise in
      failure to achieve a clinical pregnancy with the use of autologous oocytes (P<
      0.0001), but no difference with the use of donor oocytes. Among women using
      autologous oocytes who did conceive, failure to achieve a live birth increased
      with increasing obesity, to a greater extent among women <35 years of age.
      CONCLUSIONS: Higher BMI is associated with an increased failure to achieve a
      clinical intrauterine gestation; this risk was overcome with the use of donor
      oocytes. Failure to achieve a live birth increases with higher BMI, significantly
      with the use of autologous oocytes (P< 0.0001), and to a greater extent among
      women <35 years of age (P< 0.0001).

PMID- 21071490
TI  - 'Waiting for Godot': a commonsense approach to the medical treatment of
      endometriosis.
AB  - Conservative surgical treatment for symptomatic endometriosis is frequently
      associated with only partial relief of pelvic pain or its recurrence. Therefore,
      medical therapy constitutes an important alternative or complement to surgery.
      However, no available compound is cytoreductive, and suppression instead of
      elimination of implants is the only realistic objective of pharmacological
      intervention. Because this implies prolonged periods of treatments, only
      medications with a favourable safety/tolerability/efficacy/cost profile should be
      chosen. In the past few years, innumerable new drugs for endometriosis, which
      would interfere with several hypothesized pathogenic mechanisms, have been
      studied and their use foreseen. However, robust evidence of in vivo safety and
      efficacy is lacking and, at the moment, the principal modality to interfere with
      endometriosis metabolism is still hormonal manipulation. Regrettably, in spite of
      consistent demonstration of a major effect on pain even in patients with deeply
      infiltrating lesions, progestins are underestimated and dismissed in favour of
      more scientifically fashionable and up-to-the-minute alternatives. Moreover, oral
      contraceptives (OCs) dramatically reduce the rate of post-operative endometrioma
      recurrence and should now be considered an essential part of long-term
      therapeutic strategies in order to limit further damage to future fertility.
      Finally, women who have used OC for prolonged periods will be protected from an
      increased risk of endometriosis-associated ovarian cancer. To avoid the several
      subtle modalities for distorting facts and orientating opinions in favour of
      specific compounds, progestins and monophasic OC used continuously are here
      proposed as the reference comparator in all future randomized controlled trials
      on medical treatment for endometriosis.

PMID- 21071491
TI  - Fertility treatments and the young women who use them: an Australian cohort
      study.
AB  - BACKGROUND: In Australia, fertility treatment is partly or wholly reimbursable
      under federal benefits schemes, without restrictions on age, number of treatment
      cycles or existing family size. In this study, we aimed to characterize the
      potential need for and use of fertility treatments in a population-based cohort
      of young Australian women. METHODS: We conducted structured interviews with 974
      members of a cohort constructed by tracing all female infants born at a single
      general hospital in Adelaide between 1973 and 1975. The main outcome measures
      were pregnancy history, difficulty becoming pregnant and assistance sought to
      become pregnant. RESULTS: Of 657 women aged 30-32 who had sought pregnancy, 24%
      reported difficulty becoming pregnant and 26% had lost at least one pregnancy.
      Ovulatory problems (16%) and male fertility problems (13%) were common among
      those with difficulty. Over half of the women who had difficulty conceiving (58%)
      sought assistance, largely from specialists (53%). Consultations, tests and
      education only were common (22%), as were IVF/ICSI (17%). Close to a third (28%)
      of those seeking assistance were treated only with clomiphene, as were two-thirds
      (67%) of women with ovulatory problems. CONCLUSIONS: In this study, almost a
      quarter of women in their early 30s reported difficulty conceiving, and over a
      quarter reported pregnancy loss. This suggests that a significant proportion of
      young women experience substantial difficulties becoming pregnant. Our findings
      highlight the need to continue to document the range of women's reproductive
      experiences and to monitor fertility and treatment-seeking trends.

PMID- 21071492
TI  - Physiological role of the respiratory quinol oxidase in the anaerobic nitrite
      reducing methanotroph 'Candidatus Methylomirabilis oxyfera'.
AB  - The anaerobic nitrite-reducing methanotroph 'Candidatus Methylomirabilis oxyfera'
      ('Ca. M. oxyfera') produces oxygen from nitrite by a novel pathway. The major
      part of the O(2) is used for methane activation and oxidation, which proceeds by
      the route well known for aerobic methanotrophs. Residual oxygen may serve other
      purposes, such as respiration. We have found that the genome of 'Ca. M. oxyfera'
      harbours four sets of genes encoding terminal respiratory oxidases: two
      cytochrome c oxidases, a third putative bo-type ubiquinol oxidase, and a cyanide
      insensitive alternative oxidase. Illumina sequencing of reverse-transcribed total
      community RNA and quantitative real-time RT-PCR showed that all four sets of
      genes were transcribed, albeit at low levels. Oxygen-uptake and inhibition
      experiments, UV-visible absorption spectral characteristics and EPR spectroscopy
      of solubilized membranes showed that only one of the four oxidases is
      functionally produced by 'Ca. M. oxyfera', notably the membrane-bound bo-type
      terminal oxidase. These findings open a new role for terminal respiratory
      oxidases in anaerobic systems, and are an additional indication of the
      flexibility of terminal oxidases, of which the distribution among anaerobic micro
      organisms may be largely underestimated.

PMID- 21071493
TI  - Fur regulation of the capsular polysaccharide biosynthesis and iron-acquisition
      systems in Klebsiella pneumoniae CG43.
AB  - The ferric uptake regulator Fur has been reported to repress the expression of
      rmpA, a regulatory gene for the mucoid phenotype, leading to decreased capsular
      polysaccharide (CPS) biosynthesis in Klebsiella pneumoniae CG43. Here,
      quantitative real-time PCR (qRT-PCR) analyses and electrophoretic mobility shift
      assays showed that Fur also repressed the expression of the CPS regulatory genes
      rmpA2 and rcsA. Interestingly, deletion of rmpA or rcsA but not rmpA2 from the
      Deltafur strain was able to suppress the deletion effect of Fur. The availability
      of extracellular iron affected the amount of CPS, suggesting that Fur regulates
      CPS biosynthesis in an Fe(II)-dependent manner. Increased production of
      siderophores was observed in the Deltafur strain, suggesting that uptake of
      extracellular iron in K. pneumoniae is regulated by Fur. Fur titration assays and
      qRT-PCR analyses demonstrated that at least six of the eight putative iron
      acquisition systems, identified by a blast search in the contig database of K.
      pneumoniae CG43, were directly repressed by Fur. We conclude that Fur has a dual
      role in the regulation of CPS biosynthesis and iron acquisition in K. pneumoniae.

PMID- 21071494
TI  - An alkylaminoquinazoline restores antibiotic activity in Gram-negative resistant
      isolates.
AB  - To date, various bacterial drug efflux pump inhibitors (EPIs) have been
      described. They exhibit variability in their activity spectrum with respect to
      antibiotic structural class and bacterial species. Among the various 4
      alkylaminoquinazoline derivatives synthesized and studied in this work, one
      molecule, 1167, increased the susceptibility of important human-pathogenic,
      resistant, Gram-negative bacteria towards different antibiotic classes. This 4-(3
      morpholinopropylamino)-quinazoline induced an increase in the activity of
      chloramphenicol, nalidixic acid, norfloxacin and sparfloxacin, which are
      substrates of the AcrAB-TolC and MexAB-OprM efflux pumps that act in these
      multidrug-resistant isolates. In addition, 1167 increased the intracellular
      concentration of chloramphenicol in efflux pump-overproducing strains. The rate
      of restoration depended on the structure of the antibiotic, suggesting that
      different sites in the efflux pumps may be involved. A molecule exhibiting a
      morpholine functional group and a propyl extension of the side chain was more
      active.

PMID- 21071495
TI  - The interaction between a non-pathogenic and a pathogenic strain synergistically
      enhances extra-intestinal virulence in Escherichia coli.
AB  - Finding two or more genotypes of a single species within an infected sample is a
      not infrequent event. In this work, three Escherichia coli strains of decreasing
      extra-intestinal virulence (pathogenic B2S and B1S strains, and the avirulent K
      12 MG1655 strain) were tested in septicaemia and urinary tract infection (UTI)
      mouse models, either separately or in pairs. Survival was monitored and bacteria
      were counted in various organs. Serum interleukin (IL)-6, tumour necrosis factor
      alpha (TNFalpha) and IL-10 were measured. We show that a mix of high amounts of
      B1S or of MG1655 with low amounts of B2S killed more rapidly (B1S), or killed
      more mice (MG1655), than either high amounts of B1S, high amounts of MG1655 or
      low amounts of B2S separately in the mouse septicaemia model. This bacterial
      synergy persisted when high amounts of dead or abnormal-LPS K-12 cells were
      injected together with a low amount of B2S. In both septicaemia and UTI models,
      significantly more bacteria were recovered from the organs of mice injected with
      the MG1655/B2S mix than from those of mice injected with the inocula separately.
      Consistently, in the septicaemia model, more IL-6 was secreted before death by
      the mice that were injected with the mix of bacteria than by the mice that were
      injected with the inocula separately. The synergistically enhanced mortality in
      the case of co-infection in the septicaemia model persisted in RFcgamma(-/-),
      Myd88(-/-) and IL-6(-/-) knockout mice. This synergistically increased virulence
      resulting from the interaction between an avirulent and a pathogenic strain of
      the same bacterial species raises questions about the role of avirulent bacteria
      in the development of some extra-intestinal infections.

PMID- 21071496
TI  - N-Acylhomoserine lactone quorum-sensing signalling in antagonistic phenazine
      producing Pseudomonas isolates from the red cocoyam rhizosphere.
AB  - Forty fluorescent Pseudomonas strains isolated from white and red cocoyam roots
      were tested for their ability to synthesize N-acyl-l-homoserine lactones (acyl
      HSLs). Remarkably, only isolates from the red cocoyam rhizosphere that were
      antagonistic against the cocoyam root rot pathogen Pythium myriotylum and
      synthesized phenazine antibiotics produced acyl-HSLs. This supports the
      assumption that acyl-HSL production is related to the antagonistic activity of
      the strains. After detection, the signal molecules were identified through TLC
      overlay and liquid chromatography-multiple MS (LC-MS/MS) analysis. In our
      representative strain, Pseudomonas CMR12a, production of the signal molecules
      could be assigned to two quorum-sensing (QS) systems. The first one is the QS
      system for phenazine production, PhzI/PhzR, which seemed to be well conserved,
      since it was genetically organized in the same way as in the well-described
      phenazine-producing Pseudomonas strains Pseudomonas fluorescens 2-79, Pseudomonas
      chlororaphis PCL1391 and Pseudomonas aureofaciens 30-84. The newly characterized
      genes cmrI and cmrR make up the second QS system of CMR12a, under the control of
      the uncommon N-3-hydroxy-dodecanoyl-homoserine lactone (3-OH-C12-HSL) and with
      low similarity to other Pseudomonas QS systems. No clear function could yet be
      assigned to the CmrI/CmrR system, although it contributes to the biocontrol
      capability of CMR12a. Both the PhzI/PhzR and CmrI/CmrR systems are controlled by
      the GacS/GacA two-component regulatory system.

PMID- 21071497
TI  - Continued improvement in myocardial T2* over two years of deferasirox therapy in
      beta-thalassemia major patients with cardiac iron overload.
AB  - BACKGROUND: The efficacy of cardiac iron chelation in transfusion-dependent
      patients has been demonstrated in one-year prospective trials. Since
      normalization of cardiac T2* takes several years, the efficacy and safety of
      deferasirox was assessed for two years in patients with beta-thalassemia major in
      the cardiac sub-study of the EPIC trial. DESIGN AND METHODS: Eligible patients
      with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with
      the primary endpoint being the change in T2* from baseline to two years. RESULTS:
      Baseline myocardial T2* was severe (> 5 to < 10 ms) in 39 patients, and moderate
      to-mild (10 to < 20 ms) in 62 patients. Mean deferasirox dose was 33.1 +/- 3.7
      mg/kg/d in the one-year core study increasing to 36.1 +/- 7.7 mg/kg/d during the
      second year of treatment. Geometric mean myocardial T2* increased from a baseline
      of 11.2 to 14.8 ms at two years (P < 0.001). In patients with moderate-to-mild
      baseline T2*, an increase was seen from 14.7 to 20.1 ms, with normalization (>=
      20 ms) in 56.7% of patients. In those with severe cardiac iron overload at
      baseline, 42.9% improved to the moderate-to-mild group. The incidence of drug
      related adverse events did not increase during the extension relative to the core
      study and included (>= 5%) increased serum creatinine, rash and increased alanine
      aminotransferase. CONCLUSIONS: Continuous treatment with deferasirox for two
      years with a target dose of 40 mg/kg/d continued to remove iron from the heart in
      patients with beta-thalassemia major and mild, moderate and severe cardiac
      siderosis. (Clinicaltrials.gov identifier: NCT 00171821).

PMID- 21071498
TI  - Glucose availability in hypoxia regulates the selection of chronic myeloid
      leukemia progenitor subsets with different resistance to imatinib-mesylate.
AB  - BACKGROUND: Incubation of chronic myeloid leukemia cells in hypoxia inhibits
      growth and selects BCR/Abl-independent cells with stem cell properties which are
      refractory to imatinib-mesylate. This study aimed to characterize the
      relationship of this refractoriness with glucose availability in the environment.
      DESIGN AND METHODS: K562 or primary chronic myeloid leukemia cells were cultured
      at 0.1% O(2), different cell densities and glucose concentrations. The stem and
      progenitor cell potential of these cultures at different times of incubation in
      relation to BCR/Abl(protein) expression and sensitivity to imatinib-mesylate was
      explored by transferring cells to growth-permissive secondary cultures in
      normoxia, according to the Culture-Repopulating Ability assay methodology.
      RESULTS: Hypoxia-resistant cells maintained BCR/Abl(protein) expression until
      glucose was no longer available in primary hypoxic cultures, where glucose
      availability appeared to regulate cell number and the balance between the
      enrichment of cells with kinetic properties typical of stem or progenitor cells.
      Cells surviving merely hypoxic conditions were, upon transfer to secondary
      cultures, immediately available for numerical expansion due to the maintained
      BCR/Abl(protein) expression, and were consequently sensitive to imatinib
      mesylate. Instead, BCR/Abl(protein)-negative cells selected in primary cultures
      under oxygen/glucose shortage underwent a delayed numerical expansion in
      secondary cultures, which was completely refractory to imatinib-mesylate. Cells
      with the latter properties were also found in primary chronic myeloid leukemia
      explants. CONCLUSIONS: Glucose shortage in hypoxia was shown to represent the
      condition selecting BCR/Abl(protein)-negative cells refractory to imatinib
      mesylate from either chronic myeloid leukemia lines or patients. These cells,
      exhibiting stem cell properties in vitro, are metabolically suited to home to
      stem cell niches in vivo and so may represent the chronic myeloid leukemia cell
      subset responsible for minimal residual disease.

PMID- 21071499
TI  - Outcomes after related and unrelated umbilical cord blood transplantation for
      hereditary bone marrow failure syndromes other than Fanconi anemia.
AB  - BACKGROUND: Allogeneic stem cell transplantation is the only curative option for
      patients with hereditary bone marrow failure syndromes. Umbilical cord blood is
      an alternative source of stem cells for allogeneic transplantation. DESIGN AND
      METHODS: This multicenter, retrospective study is based on data reported to the
      Eurocord Registry about patients with hereditary bone marrow failure syndrome who
      underwent umbilical cord blood transplantation. RESULTS: Sixty-four patients with
      hereditary bone marrow failure syndromes were transplanted from related (n = 20)
      or unrelated donors (n = 44). Diagnoses were Diamond-Blackfan anemia (21
      patients), congenital amegakaryocytic thrombocytopenia (16 patients),
      dyskeratosis congenita (8 patients), Shwachman-Diamond syndrome (2 patients),
      severe congenital neutropenia (16 patients) and unclassified (1 patient). In the
      group of patients who received grafts from related donors, all patients but one
      received an HLA-matched sibling transplant. The median number of total nucleated
      cells infused was 5 * 107/kg. The cumulative incidence of neutrophil recovery at
      60 days was 95%. Two patients had grade II-IV acute graft-versus-host disease,
      while the 2-year cumulative incidence of chronic graft-versus-host disease was
      11%. The 3-year overall survival rate was 95%. In the group of patients who
      received grafts from unrelated donors, 86% had HLA-mismatched grafts and three
      received two umbilical cord blood units. The median number of total nucleated
      cells infused was 6.1 * 107/kg. The cumulative incidence of neutrophil recovery
      at day 60 in this group was 55%. The 100-day cumulative incidence of grade II-IV
      acute graft-versus-host disease was 24%, while the 2-year cumulative incidence of
      chronic graft-versus-host disease was 53%. The 3-year overall survival rate was
      61%; better overall survival was associated with age less than 5 years (P = 0.01)
      and 6.1 * 107/kg or more total nucleated cells infused (P = 0.05). CONCLUSIONS:
      In patients with hereditary bone marrow failure syndromes, related umbilical cord
      blood transplantation is associated with excellent outcomes while increasing cell
      dose and better HLA matching might provide better results in unrelated umbilical
      cord blood transplantation.

PMID- 21071500
TI  - Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr
      virus status in classical Hodgkin's lymphoma.
AB  - BACKGROUND: Classical Hodgkin's lymphoma is characterized by a minority of
      neoplastic cells surrounded by a heterogeneous background population of non
      neoplastic cells including lymphoma-associated macrophages. High levels of
      expression of both the monocyte/macrophage lineage-associated antigens CD68 and
      CD163 have been suggested to have pro-tumor effects. The aim of our study was to
      correlate expression of CD68 and CD163 with the clinico-pathological features and
      prognosis of a cohort of patients with previously untreated Hodgkin's lymphoma.
      DESIGN AND METHODS: A tissue microarray was constructed from paraffin-embedded
      tumor tissues from 288 cases of classical Hodgkin's lymphoma. CD68 and CD163
      expression was assessed immunohistochemically and the degree of macrophage
      infiltration within the tumor was scored using point grid counting. Clinical data
      were obtained from clinical records. RESULTS: The patients' median age was 37
      years (range, 6-86 years). The male to female ratio was 1.2. In classical
      Hodgkin's lymphoma (n = 288) high CD68 and CD163 expression correlated, at the
      univariate level, with poorer overall survival (P=0.002 and P=0.03, respectively)
      and event-free survival (P=0.03 and P=0.04, respectively). At the multivariate
      level, high CD68 expression remained significantly predictive of overall survival
      (P=0.004). In addition, we demonstrated that both high CD68 and CD163 expression
      were associated with the presence of Epstein-Barr virus in the neoplastic cells
      (P=0.001 and P=0.0002, respectively). CONCLUSIONS: In classical Hodgkin's
      lymphoma, high expression of the macrophage/monocyte-related antigens CD68 and
      CD163 correlates with adverse outcome and with the presence of Epstein-Barr virus
      in the tumor cell population.

PMID- 21071501
TI  - Prognostic factors for intensive care unit admission, intensive care outcome, and
      post-intensive care survival in patients with de novo acute myeloid leukemia: a
      single center experience.
AB  - BACKGROUND: Acute myeloid leukemia is a life-threatening disease associated with
      high mortality rates. A substantial number of patients require intensive care.
      This investigation analyzes risk factors predicting admission to the intensive
      care unit in patients with acute myeloid leukemia eligible for induction
      chemotherapy, the outcome of these patients, and prognostic factors predicting
      their survival. DESIGN AND METHODS: A total of 406 consecutive patients with de
      novo acute myeloid leukemia (15-89 years) were analyzed retrospectively. Markers
      recorded at the time of diagnosis included karyotype, fibrinogen, C-reactive
      protein, and Charlson comorbidity index. In patients requiring critical care, the
      value of the Simplified Acute Physiology Score II, the need for mechanical
      ventilation, and vasopressor support were recorded at the time of intensive care
      unit admission. The independent prognostic relevance of the parameters was tested
      by multivariate analysis. RESULTS: Sixty-two patients (15.3%) required intensive
      care, primarily due to respiratory failure (50.0%) or life-threatening bleeding
      (22.6%). Independent risk factors predicting intensive care unit admission were
      lower fibrinogen concentration, the presence of an infection, and comorbidity.
      The survival rate was 45%, with the Simplified Acute Physiology Score II being
      the only independent prognostic parameter (P<0.05). Survival was inferior in
      intensive care patients compared to patients not admitted to an intensive care
      unit. However, no difference between intensive care and non-intensive care
      patients was found concerning continuous complete remission at 6 years or
      survival at 6 years in patients who survived the first 30 days after diagnosis
      (non-intensive care patients: 28%; intensive care patients: 20%, P>0.05).
      CONCLUSIONS: Ongoing infections, low fibrinogen and comorbidity are predictive
      for intensive care unit admission in acute myeloid leukemia. Although admission
      was a risk factor for survival, continuous complete remission and survival of
      patients alive at day 30 were similar in patients who were admitted or not
      admitted to an intensive care unit.

PMID- 21071502
TI  - Impact of invasive fungal disease on the chemotherapy schedule and event-free
      survival in acute leukemia patients who survived fungal disease: a case-control
      study.
AB  - Patients with acute leukemia who initially survive invasive fungal disease must
      receive chemotherapy or go on to transplant. Many centers change subsequent
      chemotherapy to decrease the risk of fungal reactivation. This case-control study
      compared acute leukemia patients (n=28) who developed a proven or probable fungal
      disease and survived four weeks later, to patients who did not (n=78), and
      assessed the impact of fungal disease on the chemotherapy regimens, and overall
      and event-free survival. Chemotherapy changes (i.e. delays, dose-reduction) were
      more frequent in the fungal (68%) than in the control group (24%) (P<0.001).
      Although there was no difference in overall and event-free survival between
      groups, they were both lower for proven fungal disease cases when compared to
      controls (HR 2.4, 95% CI 1.1-1.5, and HR 2.9, 95% CI 1.4-5.6, respectively).
      Patients with invasive fungal disease, even though they initially survive,
      undergo significant changes to their chemotherapy therapy. This impacts on the
      survival of patients with proven fungal disease.

PMID- 21071503
TI  - Experimental evidence supporting the concept of light-mediated modulation of stem
      hydraulic conductance.
AB  - It is a well-described phenomenon that plant leaves respond to changes in light
      intensity and duration by adjusting leaf hydraulic efficiency, and there is
      current consensus that up- or down-regulation of water channels (aquaporins) in
      the plasma membrane of the bundle sheath and mesophyll cells play a central role
      in the underlying mechanisms. Recently, experimental evidence has been provided
      also for light-mediated changes of stem hydraulic conductance (K(stem)) in field
      grown laurel plants. This effect was attributed to differences in potassium ion
      concentration of xylem sap as a function of light conditions. In the present
      article, we report evidence obtained in silver birch (Betula pendula Roth),
      supporting the concept of light-mediated modulation of K(stem). Both canopy
      position (long-term effect) and current photosynthetic photon flux density (PPFD;
      short-term effect) had a significant impact (P < 0.001) on K(stem) measured in
      shoots taken from the lower (shade shoots) and upper (sun shoots) third of the
      crowns of ~25-year-old trees growing in a natural forest stand. The shade shoots
      responded more sensitively to light manipulation: K(stem) increased by 51% in
      shade shoots and 26% in sun shoots when PPFD increased from 70 to 330 MUmol m-2 s
      1. In 4-year-old trees growing in a dense experimental plantation, K(stem),
      specific conductivity of branch-wood (k(bw)) and potassium ion concentration
      ([K(+)]) in xylem sap varied in accordance with canopy position (P < 0.001). Both
      K(stem) and k(bw) increased considerably with light availability, increasing
      within the tree crowns from bottom to top; there was a strong relationship
      between mean values of K(stem) and [K(+)] in hydraulically sampled branches.

PMID- 21071504
TI  - Patient satisfaction with musculoskeletal physical therapy care: a systematic
      review.
AB  - BACKGROUND: Patient satisfaction is an important patient-centered health outcome.
      To date, no systematic review of the literature on patient satisfaction with
      musculoskeletal physical therapy care has been conducted. PURPOSE: The purpose of
      this study was to systematically and critically review the literature to
      determine the degree of patient satisfaction with musculoskeletal physical
      therapy care and factors associated with satisfaction. DATA SOURCES: The
      databases CINAHL, MEDLINE, and EBM Reviews were searched from inception to
      September 2009. STUDY SELECTION: Articles were included if the design was a
      clinical trial, observational study, survey, or qualitative study; patient
      satisfaction was evaluated; and the study related to the delivery of
      musculoskeletal physical therapy services conducted in an outpatient setting. The
      search located 3,790 citations. Fifteen studies met the inclusion criteria. DATA
      EXTRACTION: Two authors extracted patient satisfaction data and details of each
      study. DATA SYNTHESIS: A meta-analysis of patient satisfaction data from 7
      studies was conducted. The pooled estimate of patient satisfaction was 4.44 (95%
      confidence interval=4.41-4.46) on a scale of 1 to 5, where 5 indicates high
      satisfaction and 1 indicates high dissatisfaction. Additional data were
      summarized in tables and critically appraised. LIMITATIONS: Nonrespondent bias
      from individual studies may affect the accuracy and representativeness of these
      data. CONCLUSION: Patients are highly satisfied with musculoskeletal physical
      therapy care delivered across outpatient settings in northern Europe, North
      America, the United Kingdom, and Ireland. The interpersonal attributes of the
      therapist and the process of care are key determinants of patient satisfaction.
      An unexpected finding was that treatment outcome was infrequently and
      inconsistently associated with patient satisfaction. Physical therapists can
      enhance the quality of patient-centered care by understanding and optimizing
      these determinants of patient satisfaction.

PMID- 21071505
TI  - Predictors of the use of physical therapy services among patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Although physical therapy is a proven and recommended intervention
      for managing rheumatoid arthritis (RA), few studies have explored correlates of
      physical therapy service use among people with RA. OBJECTIVE: The purposes of
      this study were: (1) to describe physical therapy use among people with RA and
      (2) to identify biopsychosocial factors associated with physical therapy use. It
      was expected that use of physical therapy services would be lower than previously
      reported, considering recent medical advancements, and that including contextual
      factors may lead to identification of new factors associated with physical
      therapy use. DESIGN: This was a cohort study. METHODS: Of 1,032 patients
      prospectively recruited from a large hospital registry, 772 completed baseline
      and laboratory assessments, received a physical examination, and completed a 1
      year follow-up survey regarding physical therapy service use. Measures included:
      demographics (ie, age, sex, marital status, race, employment, disability status,
      insurance, income, comorbidities, and education), disease duration, RA
      medications, self-efficacy (assessed with the Arthritis Self-Efficacy Scale),
      social support (assessed with the Berkman-Syme Social Network Index), function
      (assessed with the Multi-Dimensional Health Assessment Questionnaire), and
      disease activity (assessed with the Rheumatoid Arthritis Disease Activity Index).
      Self-reported use of physical therapy (yes/no) was assessed at the 1-year follow
      up. A staged regression approach, based on a theoretical model, was used to
      select and enter variables into the regression to develop a parsimonious set of
      predictors. RESULTS: The patients were well educated and had modestly high
      incomes, and most had health insurance. Approximately 15.3% of the patients used
      physical therapy services during the designated follow-up period. Using
      multivariable modeling, the most significant predictors of physical therapy
      service use were moderate to high disease activity (odds ratio [OR]=1.4, 95%
      confidence interval [CI]=1.1-1.8), less than a college education (OR=0.5, 95%
      CI=0.2-0.8), greater social networks (OR=2.1, 95% CI=1.3-3.5), and being on
      disability (OR=2.4, 95% CI=1.3-4.6). LIMITATIONS: The limitations of this study
      were use of a convenience sample and the potential for misclassification of
      physical therapy service use. CONCLUSIONS: Patients with less than college
      education were less likely to receive physical therapy services, and those with
      more active disease, those who were on disability, and those who had greater
      social networks were more likely to receive physical therapy services.

PMID- 21071506
TI  - Functional gait assessment and balance evaluation system test: reliability,
      validity, sensitivity, and specificity for identifying individuals with Parkinson
      disease who fall.
AB  - BACKGROUND: Gait impairments, balance impairments, and falls are prevalent in
      individuals with Parkinson disease (PD). Although the Berg Balance Scale (BBS)
      can be considered the reference standard for the determination of fall risk, it
      has a noted ceiling effect. Development of ceiling-free measures that can assess
      balance and are good at discriminating "fallers" from "nonfallers" is needed.
      OBJECTIVE: The purpose of this study was to compare the Functional Gait
      Assessment (FGA) and the Balance Evaluation Systems Test (BESTest) with the BBS
      among individuals with PD and evaluate the tests' reliability, validity, and
      discriminatory sensitivity and specificity for fallers versus nonfallers. DESIGN:
      This was an observational study of community-dwelling individuals with idiopathic
      PD. METHODS: The BBS, FGA, and BESTest were administered to 80 individuals with
      PD. Interrater reliability (n=15) was assessed by 3 raters. Test-retest
      reliability was based on 2 tests of participants (n=24), 2 weeks apart.
      Intraclass correlation coefficients (2,1) were used to calculate reliability, and
      Spearman correlation coefficients were used to assess validity. Cutoff points,
      sensitivity, and specificity were based on receiver operating characteristic
      plots. RESULTS: Test-retest reliability was .80 for the BBS, .91 for the FGA, and
      .88 for the BESTest. Interrater reliability was greater than .93 for all 3 tests.
      The FGA and BESTest were correlated with the BBS (r=.78 and r=.87, respectively).
      Cutoff scores to identify fallers were 47/56 for the BBS, 15/30 for the FGA, and
      69% for the BESTest. The overall accuracy (area under the curve) for the BBS,
      FGA, and BESTest was .79, .80, and .85, respectively. LIMITATIONS: Fall reports
      were retrospective. CONCLUSION: Both the FGA and the BESTest have reliability and
      validity for assessing balance in individuals with PD. The BESTest is most
      sensitive for identifying fallers.

PMID- 21071507
TI  - Paracrine modulation of cholangiocyte serotonin synthesis orchestrates biliary
      remodeling in adults.
AB  - Paracrine signaling between cholangiocytes and stromal cells regulates biliary
      remodeling. Cholangiocytes have neuroepithelial characteristics and serotonin
      receptor agonists inhibit their growth, but whether they are capable of serotonin
      biosynthesis is unknown. We hypothesized that cholangiocytes synthesize serotonin
      and that cross talk between liver myofibroblasts (MF) and cholangiocytes
      regulates this process to influence biliary remodeling. Transwell cultures of
      cholangiocytes +/- MF, and tryptophan hydroxylase-2 knockin (TPH2KI) mice with an
      inactivating mutation of the neuronal tryptophan hydroxylase (TPH) isoform, TPH2,
      were evaluated. Results in the cell culture models confirm that cholangiocytes
      have serotonin receptors and demonstrate for the first time that these cells
      express TPH2 and produce serotonin, which autoinhibits their growth but
      stimulates MF production of TGF-beta(1). Increased TGF-beta(1), in turn,
      counteracts autocrine inhibition of cholangiocyte growth by repressing
      cholangiocyte TPH2 expression. Studies of TPH2KI mice confirm that TPH2-mediated
      production of serotonin plays an important role in remodeling damaged bile ducts
      because mice with decreased TPH2 function have reduced biliary serotonin levels
      and exhibit excessive cholangiocyte proliferation, accumulation of aberrant
      ductules and liver progenitors, and increased liver fibrosis after bile duct
      ligation. This new evidence that cholangiocytes express the so-called neuronal
      isoform of TPH, synthesize serotonin de novo, and deploy serotonin as an
      autocrine/paracrine signal to regulate regeneration of the biliary tree
      complements earlier work that revealed that passive release of serotonin from
      platelets stimulates hepatocyte proliferation. Given the prevalent use of
      serotonin-modulating drugs, these findings have potentially important
      implications for recovery from various types of liver damage.

PMID- 21071508
TI  - Use of NBD-cholesterol to identify a minor but NPC1L1-independent cholesterol
      absorption pathway in mouse intestine.
AB  - The importance of Niemann-Pick C1 Like-1 (NPC1L1) protein in intestinal
      absorption of dietary sterols, including both cholesterol and phytosterols, is
      well documented. However, the exact mechanism by which NPC1L1 facilitates
      cholesterol transport remains controversial. This study administered 22-(N(-7
      nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBD
      cholesterol) and [(3)H]cholesterol to Npc1l1(+/+) and Npc1l1(-/-) mice to
      determine whether NPC1L1 facilitates dietary sterol uptake by enterocytes and/or
      participates in intracellular sterol delivery to the endoplasmic reticulum (ER)
      for lipoprotein assembly before secretion into plasma circulation. Results showed
      that [(3)H]cholesterol absorption was reduced but not abolished in Npc1l1(-/-)
      mice compared with Npc1l1(+/+) mice. In the presence of Pluronic L-81 to block
      pre-chylomicron exit from the ER, significant amounts of [(3)H]cholesterol were
      found to be associated with lipid droplets in the intestinal mucosa of both
      Npc1l1(+/+) and Npc1l1(-/-) mice, and the intracellular [(3)H]cholesterol can be
      esterified to cholesteryl esters. These results provided evidence indicating that
      the main function of NPC1L1 is to promote cholesterol uptake from the intestinal
      lumen but that it is not necessary for intracellular cholesterol transport to the
      ER. Surprisingly, NBD-cholesterol was taken up by intestinal mucosa, esterified
      to NBD-cholesteryl esters, and transported to plasma circulation to similar
      extent between Npc1l1(+/+) and Npc1l1(-/-) mice. Ezetimibe treatment also had no
      impact on NBD-cholesterol absorption by Npc1l1(+/+) mice. Thus, NBD-cholesterol
      absorption proceeds through an NPC1L1-independent and ezetimibe-insensitive
      sterol absorption mechanism. Taken together, these results indicate that NBD
      cholesterol can be used to trace the alternative cholesterol absorption pathway
      but is not suitable for tracking NPC1L1-mediated cholesterol absorption.

PMID- 21071509
TI  - Fructose-maltodextrin ratio in a carbohydrate-electrolyte solution differentially
      affects exogenous carbohydrate oxidation rate, gut comfort, and performance.
AB  - Solutions containing multiple carbohydrates utilizing different intestinal
      transporters (glucose and fructose) show enhanced absorption, oxidation, and
      performance compared with single-carbohydrate solutions, but the impact of the
      ratio of these carbohydrates on outcomes is unknown. In a randomized double-blind
      crossover, 10 cyclists rode 150 min at 50% peak power, then performed an
      incremental test to exhaustion, while ingesting artificially sweetened water or
      one of three carbohydrate-salt solutions comprising fructose and maltodextrin in
      the respective following concentrations: 4.5 and 9% (0.5-Ratio), 6 and 7.5% (0.8
      Ratio), and 7.5 and 6% (1.25-Ratio). The carbohydrates were ingested at 1.8 g/min
      and naturally (13)C-enriched to permit evaluation of oxidation rate by mass
      spectrometry and indirect calorimetry. Mean exogenous carbohydrate oxidation
      rates were 1.04, 1.14, and 1.05 g/min (coefficient of variation 20%) in 0.5-, 0.8
      , and 1.25-Ratios, respectively, representing likely small increases in 0.8-Ratio
      of 11% (90% confidence limits; +/- 4%) and 10% (+/- 4%) relative to 0.5- and 1.25
      Ratios, respectively. Comparisons of fat and total and endogenous carbohydrate
      oxidation rates between solutions were unclear. Relative to 0.5-Ratio, there were
      moderate improvements to peak power with 0.8- (3.6%; 99% confidence limits +/-
      3.5%) and 1.25-Ratio (3.0%; +/- 3.7%) but unclear with water (0.4%; +/- 4.4%).
      Increases in stomach fullness, abdominal cramping, and nausea were lowest with
      the 0.8- followed by the 1.25-Ratio solution. At high carbohydrate-ingestion
      rate, greater benefits to endurance performance may result from ingestion of 0.8-
      to 1.25-Ratio fructose-maltodextrin solutions. Small perceptible improvements in
      gut comfort favor the 0.8-Ratio and provide a clearer suggestion of mechanism
      than the relationship with exogenous carbohydrate oxidation.

PMID- 21071510
TI  - Characterization of silent afferents in the pelvic and splanchnic innervations of
      the mouse colorectum.
AB  - Hypersensitivity in inflammatory/irritable bowel syndrome is contributed to in
      part by changes in the receptive properties of colorectal afferent endings,
      likely including mechanically insensitive afferents (MIAs; silent afferents) that
      have the ability to acquire mechanosensitivity. The proportion and attributes of
      colorectal MIAs, however, have not previously been characterized. The distal ~3
      cm of colorectum with either pelvic (PN) or lumbar splanchnic (LSN) nerve
      attached was removed, opened longitudinally, pinned flat in a recording chamber,
      and perfused with oxygenated Krebs solution. Colorectal receptive endings were
      located by electrical stimulation and characterized as mechanosensitive or not by
      blunt probing, mucosal stroking, and circumferential stretch. MIA endings were
      tested for response to and acquisition of mechanosensitivity by localized
      exposure to an inflammatory soup (IS). Colorectal afferents were also tested with
      twin-pulse and repetitive electrical stimulation paradigms. PN MIAs represented
      23% of 211 afferents studied, 71% (30/42) of which acquired mechanosensitivity
      after application of IS to their receptive ending. LSN MIAs represented 33% of
      156 afferents studied, only 23% (11/48) of which acquired mechanosensitivity
      after IS exposure. Mechanosensitive PN endings uniformly exhibited significant
      twin-pulse slowing whereas LSN endings showed no significant twin-pulse
      difference. PN MIAs displayed significantly greater activity-dependent slowing
      than LSN MIAs. In conclusion, significant proportions of MIAs are present in the
      colorectal innervation; significantly more in the PN than LSN acquire
      mechanosensitivity in an inflammatory environment. This knowledge contributes to
      our understanding of the possible roles of MIAs in colon-related disorders like
      inflammatory/irritable bowel syndrome.

PMID- 21071511
TI  - Balance of meprin A and B in mice affects the progression of experimental
      inflammatory bowel disease.
AB  - MEP1A, which encodes the alpha subunit of meprin metalloproteinases, is a
      susceptibility gene for inflammatory bowel disease (IBD), and decreased
      intestinal meprin-alpha expression is associated with enhanced IBD in humans.
      Mice lacking meprin alpha (alpha knockout, alphaKO) have more severe colitis
      induced by dextran sulfate sodium (DSS) than wild-type (WT) mice, indicating an
      anti-inflammatory role for meprin A. Previous studies and those herein indicate
      the meprin B has proinflammatory activities. Therefore, mice lacking both meprin
      A and B (dKO mice) were generated to determine how their combined absence alters
      the inflammatory response to DSS. Unchallenged dKO mice grow and reproduce
      normally and have no obvious abnormal phenotype, except for a slightly elevated
      plasma albumin in both males and females and a lower urine creatinine level in
      dKO males. Upon oral administration of 3.5% DSS, the dKO mice have more severe
      colitis than the WT and betaKO mice but significantly less than the alphaKO mice.
      The dKO mice lose more weight and have elevated MPO and IL-6 activities in the
      colon compared with WT mice. Systemic inflammation, monitored by plasma nitric
      oxide levels, is absent in DSS-treated dKO mice, unlike WT mice. The severity of
      experimental IBD in dKO mice is intermediate between alphaKO and WT mice. The
      data indicate that the absence of meprin A aggravates chronic inflammation and
      the lack of meprin B affords some protection from injury. Manipulation of the
      expression of meprin gene products may have therapeutic potential.

PMID- 21071512
TI  - FMNL2 enhances invasion of colorectal carcinoma by inducing epithelial
      mesenchymal transition.
AB  - FMNL2 is a member of diaphanous-related formins that control actin-dependent
      processes such as cell motility and invasion. Its overexpression in metastatic
      cell lines and tissues of colorectal carcinoma has been associated with
      aggressive tumor development in our previous study. But its specific role in
      cancer is largely unknown. Here we report that FMNL2 is involved in epithelial
      mesenchymal transition (EMT) maintenance in human colorectal carcinoma cells. A
      positive correlation between FMNL2 and vimentin expression and an inverse
      correlation between FMNL2 and E-cadherin expression were found in colorectal
      carcinoma cell lines and cancer tissues. Specific knockdown of FMNL2 led to an
      epithelial-state transition, confirmed by the cobblestone-like phenotype,
      upregulation of E-cadherin, alpha-catenin, and gamma-catenin, and downregulation
      of vimentin, snail, slug. Loss of FMNL2 expression lowered the ability of TGF
      beta to induce cell invasion and EMT, as shown by morphology and the expression
      levels. Upregulation of vimentin, slug, snail, downregulation of E-cadherin and
      activation of receptor-Smad3 phosphorylation were observed in M5 and MDCK cells
      induced by TGF-beta, whereas altered expression of these markers was not obvious
      in FMNL2-depleting M5 cells. High levels of activation of p-MAPK and p-MEK, but
      not p-PI3K and p-AKT, were observed in SW480/FMNL2+ cells compared with control
      cells. Treatment with U0126 could abrogate the activation of p-MAPK and p-MEK,
      whereas LY294002 treatment had no effect on the PI3K/AKT pathway. In conclusion,
      these findings identify a novel EMT and tumor promoting function for FMNL2, which
      is involved in TGF-beta-induced EMT and colorectal carcinoma cell invasion via
      Smad3 effectors, or in collaboration with MAPK/MEK pathway.

PMID- 21071513
TI  - The MIF homologue D-dopachrome tautomerase promotes COX-2 expression through beta
      catenin-dependent and -independent mechanisms.
AB  - The cytokine/growth factor, macrophage migration inhibitory factor (MIF),
      contributes to pathologies associated with immune, inflammatory, and neoplastic
      disease processes. Several studies have shown an important contributing role for
      MIF-dependent COX-2 expression in the progression of these disorders. We now
      report that the MIF homologue, D-dopachrome tautomerase (D-DT), is both
      sufficient and necessary for maximal COX-2 expression in colorectal
      adenocarcinoma cell lines. D-DT-dependent COX-2 transcription is mediated in part
      by beta-catenin protein stabilization and subsequent transcription. Also
      contributing to D-DTs regulation of COX-2 expression are the activities of both c
      jun-N-terminal kinase and the MIF-interacting protein, Jab1/CSN5. Interestingly,
      D-DT-dependent beta-catenin stabilization is regulated by COX-2 expression,
      suggesting the existence of an amplification loop between COX-2- and beta-catenin
      mediated transcription in these cells. Because both COX-2- and beta-catenin
      mediated transcription are important contributors to colorectal cancer (CRC)
      disease maintenance and progression, these findings suggest a unique and novel
      regulatory role for MIF family members in CRC pathogenesis.

PMID- 21071515
TI  - Bundled-rate legislation for Medicare reimbursement for dialysis services:
      implications for anemia management with ESAs.
AB  - With the incidence of ESRD on the rise, there is a continuing need to control
      anemia-related treatment costs in dialysis patients receiving reimbursement
      through Medicare. Currently, erythropoiesis-stimulating agents (ESAs) are billed
      separately from dialysis services, potentially creating little financial
      incentive for more efficient use. The Medicare Improvement for Patients and
      Providers Act, passed by the U.S. Congress in July 2008, includes provisions
      intended to address this concern. Under this act, dialysis services will be
      reimbursed using a fully bundled, comprehensive payment system that includes all
      services currently covered in the basic composite rate, as well as certain
      separately billable items, including ESAs. A base rate of $229.63 per treatment
      has been assigned, to be individualized using case-mix adjusters. The
      implications of this new system for anemia management with ESAs continue to be
      elucidated. With fixed compensation for ESAs, management strategies that maximize
      efficiencies and, thereby, optimize cost savings will be favored. Select
      strategies may include switching from intravenous (IV) to subcutaneous routes,
      lowering Hb targets and ESA doses in hyporesponsive patients, increasing
      administration of IV iron, increasing use of home dialysis, and optimizing ESA
      dosing intervals. Once-monthly ESA therapy has potential advantages under this
      new system as an alternative to more frequently administered ESAs and may help
      achieve quality metrics in a cost-efficient manner.

PMID- 21071514
TI  - Prognostic significance of the detection of peripheral blood CEACAM5mRNA-positive
      cells by real-time polymerase chain reaction in operable colorectal cancer.
AB  - PURPOSE: To evaluate the clinical relevance of circulating CEACAM5mRNA-positive
      cells in patients with operable colorectal cancer (CRC). METHODS: Peripheral
      blood was obtained from 265 patients with operable CRC before the initiation of
      adjuvant systemic therapy from 96 normal donors and RNA prepared from the Lovo
      and ARH-77 CRC and leukemic cell lines, respectively, was used as positive and
      negative controls. The detection of CEACAM5mRNA-positive cells was done using a
      real-time PCR assay. The association with known prognostic factors and the effect
      of CEACAM5mRNA-positive cells on patients' prognosis was investigated. RESULTS:
      The analytical detection limit of the method was found to correspond to 0.7 Lovo
      cell equivalence/5 MUg RNA, with a sensitivity of 1 tumor cell/10(5) normal cells
      and a specificity of 97%. Ninety-eight (37%) patients had detectable circulating
      CEACAM5mRNA-positive cells. Detection of CEACAM5mRNA-positive cells was
      significantly associated with higher relapse rate (P < 0.001), decreased disease
      free survival (DFS; P < 0.001), higher death rate (P = 0.017), and decreased
      median overall survival (P = 0.025). Multivariate analysis revealed that the
      detection of circulating CEACAM5mRNA-positive cells was an independent prognostic
      factor for decreased DFS [HR = 3.4; 95% CI: 2.0-5.9; P < 0.001]. CONCLUSIONS:
      Detection of peripheral blood CEACAM5mRNA-positive cells is an adverse prognostic
      factor correlated with poor clinical outcome in patients with operable CRC.

PMID- 21071516
TI  - Effect of drugs on renal development.
AB  - Many nephrotoxic effects of drugs have been described, whereas the effect on
      renal development has received less attention. Nephrogenesis ceases at
      approximately 36 weeks of gestation, indicating that drugs administered to
      pregnant women and to preterm-born neonates may influence kidney development.
      Such an effect on renal development may lead to a wide spectrum of renal
      malformations (congenital anomalies of the kidney and urinary tract [CAKUT]),
      ranging from renal agenesis to a reduced nephron number. Any of these anomalies
      may have long-term sequelae, and CAKUT is the primary cause for renal replacement
      therapy in childhood. This review focuses on research into the effect of drug
      treatment during active nephrogenesis during pregnancy and in preterm-born
      infants. Because the effects of many widely used drugs have not been unraveled
      thus far, more research is needed to study the effect on renal development and
      long-term renal sequelae after drug treatment during nephrogenesis.

PMID- 21071517
TI  - Opioid and benzodiazepine use in end-stage renal disease: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Chronic pain and psychiatric disorders are common in
      dialysis patients, but the extent to which opioids and benzodiazepines are used
      is unclear. We conducted a systematic review to determine the: (1) prevalence of
      opioid and benzodiazepine use among dialysis patients; (2) reasons for use; (3)
      effectiveness of symptom control; and (4) incidence of adverse events. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Two authors reviewed all relevant
      citations in MEDLINE/EMBASE/CINAHL/BIOSIS Previews/Cochrane and hand-searched
      bibliographies. Studies after 1990 reporting prevalence estimates for opioid
      and/or benzodiazepine use in >=50 dialysis patients were included. RESULTS: We
      identified 15 studies from 12 countries over 1995 to 2006. Sample size ranged
      from 75 to 12,782. Prevalence of opioid and benzodiazepine use was variable,
      ranging from 5 to 36% (95% CI, 4.1 to 45.5%; n=10) and 8 to 26% (95% CI, 7.1 to
      27.3%; n=9), respectively. Prevalence was positively correlated with years on
      dialysis. Five studies reported on the same cohorts but gave different prevalence
      estimates. One study verified medication use through patient interviews. Reasons
      for use were reported in one study. Effectiveness of pain control varied from 17
      to 38%, and 72 to 84% of patients with significant pain had no analgesia (n=2).
      No study rigorously examined for adverse events. CONCLUSIONS: The prevalence of
      opioid and benzodiazepine use in dialysis patients is highly variable between
      centers. Further information is needed regarding the appropriateness of these
      prescriptions, adequacy of symptom control, and incidence of adverse effects in
      this population.

PMID- 21071518
TI  - Peritoneal albumin and protein losses do not predict outcome in peritoneal
      dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Peritoneal clearance of albumin-unlike the transport
      of small molecules-is defined by both vascular surface area and size-selective
      permeability. Few studies have supported a positive correlation between
      peritoneal albumin loss and mortality. The aim of this study was to investigate
      whether baseline peritoneal loss and clearance of albumin and other proteins is a
      risk factor of death in peritoneal dialysis patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: All incident peritoneal dialysis patients in our
      center during the last 15 years were included. Mass-transfer area coefficient of
      creatinine and peritoneal clearances of albumin, beta2-microglobulin, alpha2
      macroglobulin, and immunoglobulin G were calculated during a standard peritoneal
      permeability analysis. The total amount of albumin loss in the dialysate was also
      calculated. Overall mortality was studied with an intention-to-treat analysis.
      RESULTS: Two hundred fifty-seven patients were included. High baseline albumin
      clearance was associated with fast transport status, the presence of peripheral
      arterial disease, and a high comorbidity index, whereas C-reactive protein levels
      did not differ from the patients with low albumin clearance. Age, high
      comorbidity score, C-reactive protein levels >10 mg/L, and a low serum albumin
      were associated with mortality. Peritoneal albumin clearances and albumin loss
      were not associated with death in crude and adjusted analysis. Similarly,
      peritoneal clearances of immunoglobulin G, alpha2-macroglobulin, and beta2
      microglobulin were not determinants of survival. CONCLUSIONS: Baseline peritoneal
      albumin and protein clearances are associated with signs of comorbidity, but this
      does not have a measurable effect on patient survival.

PMID- 21071520
TI  - Brain tissue binding of drugs: evaluation and validation of solid supported
      porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AB  - Estimating the unbound fraction of drugs in brain has become essential for the
      evaluation and interpretation of the pharmacokinetics and pharmacodynamics of new
      central nervous system drug candidates. Dialysis-based methods are considered to
      be accurate for estimating the fraction unbound in brain; however, these
      techniques are hampered by a low throughput. In this study, we present a novel,
      matrix-free, high-throughput method for estimating the unbound fraction, based on
      a sample pooling approach combining the TRANSIL brain absorption assay with
      liquid chromatography-mass spectrometry. The base measurement of the TRANSIL
      approach is the affinity to brain membranes, and this method is used directly to
      predict the free fraction in brain. The method was evaluated by comparing the
      free fraction of drugs in brain [f(u,brain) (%)] obtained using the TRANSIL brain
      absorption assay and equilibrium dialysis methods for a test set of 65 drugs (27
      marketed and 38 proprietary drugs). A good correlation (r(2) > 0.93) of
      f(u,brain) (%) between the TRANSIL brain absorption assay and equilibrium
      dialysis was observed. Moreover, we compared the lipid composition of rat and
      porcine brain and analyzed the influence of the brain albumin content on brain
      tissue binding measurement. The comparison of the lipid composition indicated
      only minor differences between rat and porcine brain, and albumin appears to have
      a low impact on brain tissue binding measurements. The TRANSIL brain absorption
      assay with sample pooling methodology not only significantly reduces the
      biological matrix required but also increases the throughput, compared with the
      conventional dialysis methods.

PMID- 21071519
TI  - Association between hemoglobin level and endothelial function in uncomplicated,
      untreated hypertensive patients.
AB  - BACKGROUND AND OBJECTIVES: Hemoglobin (Hb) is an important nitric oxide (NO)
      buffer and a modulator of NO bioavailability. In addition, endothelial
      dysfunction is common in hypertensive patients, suggesting a pivotal role of
      hemoglobin concentration ([Hb]) in vascular function. To investigate the
      potential role of [Hb] in endothelium-dependent vasodilation, the relationship
      between Hb and endothelial function was tested in a group of patients with
      essential hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this
      retrospective study, 174 nonsmoking, uncomplicated, never-treated hypertensives
      were enrolled. Endothelium-dependent and -independent vasodilation was assessed
      by measurement of forearm blood flow response during intra-arterial infusion of
      increasing doses of acetylcholine (ACh) and sodium nitroprusside (SNP) using
      strain-gauge plethysmography. Correlation with established risk factors of
      endothelial dysfunction was performed. RESULTS: The vasodilatory response to ACh
      was inversely (P < 0.001) related to [Hb], and this relationship was dose
      dependent (P < 0.001), being minimal at the lowest dose and maximal at the
      highest dose. No association was found between Hb and the vasodilatory response
      to SNP. In a multiple linear regression model adjusted for Framingham risk
      factors (age, sex, BP, cholesterol, body mass index, glucose) and emerging risk
      factors (homeostasis model assessment index, C-reactive protein, estimated GFR),
      [Hb] maintained a strong and independent link with the vasodilatory response to
      ACh (P < 0.001). CONCLUSIONS: In a large group of nonsmoking untreated
      hypertensives, [Hb] is inversely related to forearm endothelium-dependent
      vasodilation. [Hb] should be taken into account, especially in conditions
      associated with low [Hb], when performing vascular function studies.

PMID- 21071521
TI  - Tissue distribution and elimination of [14C]apixaban in rats.
AB  - Apixaban, a potent and highly selective factor Xa inhibitor, is currently under
      development for treatment of arterial and venous thrombotic diseases. The
      distribution, metabolism, and elimination of [(14)C]apixaban were investigated in
      male, female, pregnant, and lactating rats after single oral doses. Tissue
      distribution of radioactivity in rats was measured using quantitative whole-body
      autoradiography. After a single oral administration, radioactivity distributed
      quickly in rats with C(max) at 1 h for most tissues. The elimination t(1/2) of
      radioactivity in blood was 1.7 to 4.2 h. The blood area under the plasma
      concentration-time curve of radioactivity was similar between male and female
      rats and was slightly higher in pregnant rats and lower in lactating rats. The
      radioactivity concentration in tissues involved in elimination was greater than
      that in blood with the highest concentration in the gastrointestinal tract,
      liver, and urinary bladder/contents and lowest level in brains. In pregnant rats,
      the whole-body autoradiogram showed that low levels of radioactivity were present
      in fetal blood, liver, and kidney and were much lower than the radioactivity in
      the respective maternal organs. The fecal route was the major pathway (74% of
      dose), and the urinary route was the minor pathway (14%) for apixaban
      elimination. After single oral doses of [(14)C]apixaban to lactating rats,
      apixaban exhibited extensive lacteal excretion with apixaban as the major
      component. In summary, tissue distribution of apixaban in rats was extensive but
      with limited transfer to fetal and brain tissues and extensive secretion into rat
      milk with the parent drug as the major component. Milk excretion could account
      for 10% of apixaban dose, which was comparable to urinary elimination in rats.
      Tissue distribution and drug excretion of apixaban are consistent with those for
      a moderately permeable drug that is a substrate for P-glycoprotein and breast
      cancer resistance protein efflux transporters.

PMID- 21071522
TI  - Glomerular filtration barrier and molecular segregation: guilty as charged?

PMID- 21071523
TI  - MCP-1 gene activation marks acute kidney injury.
AB  - Monocyte chemoattractant protein 1 (MCP-1) mediates acute ischemic and toxic
      kidney injury, but whether this can be used as a biomarker of acute kidney injury
      (AKI) is unknown. We obtained kidney and urine samples from mice with intrarenal
      (maleate), prerenal (endotoxemia), or postrenal (ureteral obstruction) injury. We
      also studied the independent effects of uremia without concomitant kidney injury
      by performing bilateral ureteral transection in mice. Additionally, we obtained
      urine samples from APACHE II-matched critically ill patients with or without
      advancing azotemia (n = 10 in each group). We assayed selected samples for MCP-1,
      MCP-1 mRNA, and for an activating histone mark (H3K4m3) at urinary fragments of
      the MCP-1 gene and contrasted the results with those obtained for neutrophil
      gelatinase-associated lipocalin (NGAL), a comparator "AKI biomarker" gene.
      Maleate increased urinary MCP-1 protein and mRNA more than the corresponding
      increases in NGAL. Endotoxemia and ureteral obstruction also increased NGAL and
      MCP-1 gene expression. Uremia, in the absence of renal injury, induced the NGAL
      gene, but not MCP-1, suggesting the possibility of better specificity of MCP-1
      for AKI. Clinical assessments supported the utility of MCP-1 as a biomarker
      (e.g., nonoverlapping concentrations of urinary MCP-1 in patients with and
      without AKI). Elevated levels of urinary MCP-1 mRNA and levels of H3K4m3 at the
      MCP-1 gene supported MCP-1 gene activation in patients with renal injury. In
      conclusion, these data suggest that MCP-1 has potential as a biomarker of AKI and
      provide "proof of concept" that urinary histone assessments provide mechanistic
      insight among patients with kidney disease.

PMID- 21071525
TI  - Managing overly rapid correction of chronic hyponatremia: an ounce of prevention
      or a pound of cure?

PMID- 21071524
TI  - Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary
      concentration.
AB  - The most common cause of hereditary nephrogenic diabetes insipidus is a
      nonfunctional vasopressin (VP) receptor type 2 (V2R). Calcitonin, another ligand
      of G-protein-coupled receptors, has a VP-like effect on electrolytes and water
      reabsorption, suggesting that it may affect AQP2 trafficking. Here, calcitonin
      increased intracellular cAMP and stimulated the membrane accumulation of AQP2 in
      LLC-PK1 cells. Pharmacologic inhibition of protein kinase A (PKA) and deficiency
      of a critical PKA phosphorylation site on AQP2 both prevented calcitonin-induced
      membrane accumulation of AQP2. Fluorescence assays showed that calcitonin led to
      a 70% increase in exocytosis and a 20% decrease in endocytosis of AQP2.
      Immunostaining of rat kidney slices demonstrated that calcitonin induced a
      significant redistribution of AQP2 to the apical membrane of principal cells in
      cortical collecting ducts and connecting segments but not in the inner stripe or
      inner medulla. Calcitonin-treated VP-deficient Brattleboro rats had a reduced
      urine flow and two-fold higher urine osmolality during the first 12 hours of
      treatment compared with control groups. Although this VP-like effect of
      calcitonin diminished over the following 72 hours, the tachyphylaxis was
      reversible. Taken together, these data show that calcitonin induces cAMP
      dependent AQP2 trafficking in cortical collecting and connecting tubules in
      parallel with an increase in urine concentration. This suggests that calcitonin
      has a potential therapeutic use in nephrogenic diabetes insipidus.

PMID- 21071526
TI  - The frequency and clinical significance of thrombocytopenia complicating critical
      illness: a systematic review.
AB  - BACKGROUND: The epidemiology of thrombocytopenia in critically ill patients has
      not been well characterized. The objective of this study was to systematically
      review the prevalence, incidence, and consequences of, and risk factors for,
      thrombocytopenia among critically ill patients. METHODS: We searched MEDLINE,
      EMBASE, the Cochrane Registry for controlled trials (until May 2010), and the
      Online Computer Library, as well as bibliographies of relevant studies, to
      identify investigations designed to examine the frequency, risk factors, and/or
      outcomes associated with thrombocytopenia among patients admitted to the ICU. We
      independently selected studies, abstracted data, and assessed methodologic
      quality in duplicate. Heterogeneity of design and analysis precluded statistical
      pooling of results. RESULTS: We identified 24 studies (12 prospective) enrolling
      6,894 patients from medical, surgical, mixed, or trauma ICUs. Prevalent
      thrombocytopenia (on ICU admission) occurred in 8.3% to 67.6% of patients;
      incident thrombocytopenia (developing during the course of the ICU stay) occurred
      in 13.0% to 44.1% of patients. High illness severity, sepsis, and organ
      dysfunction often correlated with thrombocytopenia. Only one study using
      multivariate analysis examined whether thrombocytopenia was associated with major
      bleeding, but it found no association. Six out of eight studies using
      multivariate analysis found that thrombocytopenia increased the risk of death.
      CONCLUSIONS: The frequency of thrombocytopenia during critical illness varies
      widely, based on case mix and definition. After confounding factors are adjusted
      for, thrombocytopenia appears to increase the risk of death.

PMID- 21071527
TI  - COPD and air travel: oxygen equipment and preflight titration of supplemental
      oxygen.
AB  - BACKGROUND: Patients with COPD may need supplemental oxygen during air travel to
      avoid development of severe hypoxemia. The current study evaluated whether the
      hypoxia-altitude simulation test (HAST), in which patients breathe 15.1% oxygen
      simulating aircraft conditions, can be used to establish the optimal dose of
      supplemental oxygen. Also, the various types of oxygen-delivery equipment allowed
      for air travel were compared. METHODS: In a randomized crossover trial, 16
      patients with COPD were exposed to alveolar hypoxia: in a hypobaric chamber (HC)
      at 2,438 m (8,000 ft) and with a HAST. During both tests, supplemental oxygen was
      given by nasal cannula (NC) with (1) continuous flow, (2) an oxygen-conserving
      device, and (3) a portable oxygen concentrator (POC). RESULTS: PaO(2) kPa (mm Hg)
      while in the HC and during the HAST with supplemental oxygen at 2 L/min (pulse
      setting 2) on devices 1 to 3 was (1) 8.6 +/- 1.0 (65 +/- 8) vs 12.5 +/- 2.4 (94
      +/- 18) (P < .001), (2) 8.6 +/- 1.6 (64 +/- 12) vs 9.7 +/- 1.5 (73 +/- 11) (P <
      .001), and (3) 7.7 +/- 0.9 (58 +/- 7) vs 8.2 +/- 1.1 (62 +/- 8) (P= .003),
      respectively. CONCLUSIONS: The HAST may be used to identify patients needing
      supplemental oxygen during air travel. However, oxygen titration using an NC
      during a HAST causes accumulation of oxygen within the facemask and
      underestimates the oxygen dose required. When comparing the various types of
      oxygen-delivery equipment in an HC at 2,438 m (8,000 ft), compressed gaseous
      oxygen with continuous flow or with an oxygen-conserving device resulted in the
      same PaO(2), whereas a POC showed significantly lower PaO(2) values. TRIAL
      REGISTRY: ClinicalTrials.gov; No.: Identifier: NCT01019538; URL:
      clinicaltrials.gov.

PMID- 21071528
TI  - Do elderly patients fare well in the ICU?
AB  - BACKGROUND: A recent update of the Mortality Probability Model (MPM)-III found
      14% of intensive care patients had age as their only MPM risk factor for hospital
      mortality. This subgroup had a low mortality rate (2% vs 14% overall), and
      pronounced differences were noted among elderly patients. This article is an
      expanded analysis of age-related mortality rates in patients in the ICU. METHODS:
      Project IMPACT data from 135 ICUs for 124,885 patients treated from 2001 to 2004
      were analyzed. Patients were stratified as elective surgical,
      emergency/unscheduled surgical, and medical and then further stratified by age
      and whether additional MPM risk factors were present or absent. RESULTS:
      Mortality rose with advancing age within all patient categories. Elective
      surgical patients without other risk factors were the least likely to die at all
      ages (0.4% for patients aged 18-29 years to 9.2% for patients aged >= 90 years),
      whereas medical patients with one or more additional risk factors had the highest
      mortality rate (12.1% for patients aged 18-29 years to 36.0% for patients aged >=
      90 years). In these two subsets, mortality rates approximately doubled in the
      elective surgical group among patients aged in their 70s (2.4%), 80s (4.3%), and
      90s (9.2%) but rose less dramatically in the medical group (27.0%, 30.7%, and
      36.0%, respectively). CONCLUSIONS: Although mortality increased with age, the
      risk differed significantly by patient subset, even among elderly patients, which
      may reflect a selection bias. Advanced age alone does not preclude successful
      surgical and ICU interventions, although the presence of serious comorbidities
      decreases the likelihood of survival to discharge for all age groups.

PMID- 21071529
TI  - Characterizing and quantifying the symptomatic features of COPD exacerbations.
AB  - BACKGROUND: There is a need for a standardized, valid, and reliable instrument
      for quantifying exacerbations of COPD. The objective of this study was to
      identify symptom items that characterize COPD exacerbations to form a new patient
      diary for evaluating exacerbation frequency, severity, and duration. METHODS:
      Twenty-three symptom items identified from patient interviews were administered
      to 410 patients with COPD aged (mean +/- SD) 65 +/- 10 years with stable FEV(1)
      of 51% predicted +/- 20% predicted and 1.8 +/- 1.8 exacerbations in the preceding
      12 months. A total of 222 patients had a physician-diagnosed exacerbation; 188
      were stable. Item-level analyses (floor and ceiling effects, criterion keying,
      item-total correlation) were used in the first stage of item reduction. Further
      reduction was conducted using Rasch model and descriptive item analyses.
      Exploratory factor analysis was performed on the items that survived the
      exclusion process. RESULTS: No item behaved differently between stable and
      exacerbation conditions. One item was removed after item-level analysis, and
      eight were removed following Rasch analysis. Together, the surviving 14 items met
      the criteria for a unidimensional measure of exacerbation severity. Internal
      consistency (person separation index) was excellent at 0.92. Post hoc exploratory
      factor analysis revealed one dominant factor, with three domains (breathlessness,
      cough and sputum, and chest symptoms) that accounted for 68% of the variance.
      CONCLUSIONS: An exacerbation appears to be a quantitative rather than qualitative
      change from the stable state. This analysis identified a range of symptoms that
      form a unidimensional construct of overall exacerbation severity. The 14 items
      identified form the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a
      daily diary for detecting and quantifying exacerbation severity in COPD.

PMID- 21071530
TI  - Integration of clinical and hemodynamic parameters in the prediction of long-term
      survival in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Current management guidelines for pulmonary arterial hypertension
      (PAH) recommend a treatment choice based primarily on World Health Organization
      (WHO) functional class. This study was designed to assess how the incorporation
      of readily obtained clinical and test-based information may significantly improve
      the prediction of outcomes over functional class alone. METHODS: Clinical and
      hemodynamic variables were assessed in 484 consecutive patients presenting with
      WHO group 1 PAH. The primary outcome measure was time to all-cause mortality over
      5 years from the index presentation (data available in all). Follow-up was
      censored at the time of lung or heart/lung transplant in 21 patients or at 5
      years. Predictors of mortality were assessed sequentially using Cox models, with
      the step-wise incorporation of clinical variables, echocardiographic, and
      catheterization findings. Results were further compared with the REVEAL (Registry
      to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease
      Management) prediction score. RESULTS: Overall median survival was 237 weeks (95%
      CI, 196-266), corresponding to 1-year, 3-year, and 5-year survival rates of 81.1%
      (77.0, 84.7), 61.1% (56.5, 65.3), and 47.9% (43.2, 52.4), respectively. The
      prediction of mortality was improved incrementally by incorporating clinical and
      echocardiographic measures with a concordance index (c-index) of 0.84 compared
      with that of 0.60 with functional class alone. The REVEAL prediction score was
      validated independently in this cohort to predict both 1-year and 5-year
      mortality. It had a prediction c-index of 0.71. CONCLUSIONS: The integration of
      routine PAH clinical (predominantly noninvasive) parameters predicts long-term
      outcome better than functional class and, hence, should be incorporated into
      medical management decisions.

PMID- 21071531
TI  - Biopsy of tiny thyroid nodules: not a question of "can we" but "should we".

PMID- 21071532
TI  - CT angiography for differentiation between intracerebral and intra-sylvian
      hematoma in patients with ruptured middle cerebral artery aneurysms.
AB  - BACKGROUND AND PURPOSE: ISHs and ICHs from ruptured MCA aneurysms can be
      difficult to distinguish on NCE-CT but may have a different impact on admission
      status and outcome. The presence of IHCEV on CTA may differentiate ISHs and ICHs.
      MATERIALS AND METHODS: Two observers independently reviewed non-contrast-enhanced
      CT scans and CTAs of 71 patients with MCA aneurysm hematomas for the site of the
      hematoma, according to predefined characteristics, and for the presence of IHCEV.
      We compared CTAs with NCE-CT scans in which both observers were confident about
      hematoma localization. We calculated kappa statistics for interobserver
      agreement, and RRs for poor clinical condition and poor outcome. RESULTS:
      Agreement for IHCEV was almost perfect (kappa, 0.87; 95% CI, 0.74-0.99). After
      consensus reading, 30 of 71 patients had IHCEV. In 28 of the 71 NCE-CT scans,
      both observers were confident as to the the site of the hematoma (kappa, 0.55;
      95% CI, 37%-73%). IHCEV were present in 10 of these 28 patients, of whom 9 had an
      ISH based on NCE-CT (positive predictive value, 90%; 95% CI, 55%-100%). In all 18
      of 28 patients without IHCEV, the hematoma was not intra-Sylvian (negative
      predictive value, 100%; 95% CI, 82%-100%). Poor admission status occurred in 50%
      of patients with IHCEV and in 60% without IHCEV (RR, 1.2; 95% CI, 0.8-1.9). Poor
      outcome occurred in 63% of patients with IHCEV and in 65% without IHCEV (RR, 1.0;
      95% CI, 0.7-1.5). CONCLUSIONS: Although CTA could reliably and accurately
      differentiate the hematoma types, admission status and outcome were similar for
      both groups.

PMID- 21071533
TI  - Aneurysm rupture following treatment with flow-diverting stents: computational
      hemodynamics analysis of treatment.
AB  - BACKGROUND AND PURPOSE: Flow-diverting approaches to intracranial aneurysm
      treatment had many promising early results, but recent apparently successful
      treatments have been complicated by later aneurysm hemorrhage. We analyzed 7
      cases of aneurysms treated with flow diversion to explore the possible rupture
      mechanisms. MATERIALS AND METHODS: CFD analysis of pre- and posttreatment
      conditions was performed on 3 giant aneurysms that ruptured after treatment and 4
      successfully treated aneurysms. Pre- and posttreatment hemodynamics were compared
      including WSS, relative blood flows, vascular resistances, and pressures, to
      identify the effects of flow-diverter placements. RESULTS: Expected reductions in
      aneurysm velocity and WSS were obtained, indicating effective flow diversion from
      the sac into the parent artery, consistent with periprocedural observations. In
      each case with postaneurysm rupture, the result of flow diversion led to an
      increase in pressure within the aneurysm. This pressure increase is related to
      larger effective resistance in the parent artery from placement of the devices
      and, in 2 cases, the reduction of a preaneurysm stenosis. CONCLUSIONS: Flow
      diversion devices can cause intra-aneurysmal pressure increases, which can
      potentially lead to rupture, especially for giant aneurysms. This relates both to
      changes in the parent artery configuration, such as reduction of a proximal
      stenosis, and to the flow diversion into higher resistance parent artery pathways
      combined with cerebral autoregulation, leading to higher pressure gradients.
      These may be important effects that should be considered when planning
      interventions. Potentially dangerous cases could be identified with angiography
      and/or patient-specific CFD models.

PMID- 21071534
TI  - Premortem diagnosis of sporadic Creutzfeldt-Jakob disease aided by positron
      emission tomography imaging.

PMID- 21071535
TI  - Flow diversion for cerebral aneurysms: a cautionary tale.

PMID- 21071536
TI  - Recovery of ophthalmoplegia after endovascular treatment of intracranial
      aneurysms.
AB  - BACKGROUND AND PURPOSE: Recovery of aneurysm induced CNP after endosaccular
      coiling has been reported in the literature. The aim of this study was to assess
      in detail the parameters that affect the outcome after endovascular treatment of
      ophthalmoplegic aneurysms due CNP. MATERIALS AND METHODS: Between November 1999
      and March 2008, 30 consecutive patients (8 men, 22 women; mean age, 54.9 years)
      presenting with CNP underwent endosaccular coiling with or without additional use
      of stents in the parent artery. Subarachnoid hemorrhage was present in 10
      patients, whereas 20 patients had unruptured aneurysms. The mean size of the
      aneurysms was 10 mm. Initial CNP was complete in 11 patients and partial in 19.
      Mean follow-up after coiling was 19 months. RESULTS: The mean interval between
      the onset of CNP and aneurysm embolization was 48 days. Fifteen patients (50%)
      had complete recovery of oculomotor function, 12 had incomplete recovery (40%),
      and 3 (10%) remained unchanged after treatment. In 4 aneurysms (13.3%), 1
      additional embolization was performed, whereas in 4 other aneurysms, 2 additional
      embolization procedures were necessary. Procedure-related permanent morbidity
      occurred in 2 patients (6.6%). CONCLUSIONS: Endosaccular coiling is an effective
      and safe method for the treatment of ophthalmoplegic aneurysms. Age, neck size,
      and time of treatment do not seem to constitute prognostic factors with respect
      to CNP recovery, though patients with small aneurysms, unruptured status, and/or
      location in the posterior circulation showed a tendency for better outcome. The
      degree of initial CNP was the only statistically significant prognostic factor
      concerning the final outcome, resulting in better recovery, in case of incomplete
      initial CNP.

PMID- 21071537
TI  - In vivo correlation of tumor blood volume and permeability with histologic and
      molecular angiogenic markers in gliomas.
AB  - BACKGROUND AND PURPOSE: Tumor angiogenesis is very heterogeneous and in vivo
      correlation of perfusion imaging parameters with angiogenic markers can help in
      better understanding the role of perfusion imaging as an imaging biomarker. The
      purpose of this study was to correlate PCT parameters such as CBV and PS with
      histologic and molecular angiogenic markers in gliomas. MATERIALS AND METHODS:
      Thirty-six image-guided biopsy specimens in 23 patients with treatment-naive
      gliomas underwent PCT examinations. We correlated MVD, MVCP, VEGFR-2 expression,
      tumor cellularity, and WHO grade of the image-guided biopsy specimens with the
      PCT parameters. Histologic sections were stained with hematoxylin-eosin, CD34,
      and VEGFR-2 and examined under a light microscope. These histologic and molecular
      angiogenic markers were correlated with perfusion parameters of the region of
      interest corresponding to the biopsy specimen. Pearson correlation coefficients
      and multiple regression analyses by using clustering methods were performed to
      assess these correlations. RESULTS: CBV showed a significant positive correlation
      with MVD (r = 0.596, P < .001), whereas PS showed a significant positive
      correlation with MVCP (r = 0.546, P = .001). Both CBV (r = 0.373, P = .031) and
      PS (r = 0.452, P = .039) also showed a significant correlation with WHO grade.
      VEGFR-2 positive specimens showed higher PS and CBV; however, neither was
      statistically significant at the .05 level. CONCLUSIONS: CBV showed a significant
      positive correlation with MVD, whereas PS showed a significant positive
      correlation with MVCP, suggesting that these 2 perfusion parameters represent
      different aspects of tumor vessels; hence, in vivo evaluation of these could be
      important in a better understanding of tumor angiogenesis.

PMID- 21071538
TI  - Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after
      flow-diversion treatment.
AB  - BACKGROUND AND PURPOSE: FD technology enables reconstructive repair of otherwise
      difficult-to-treat intracranial aneurysms. These stentlike devices may induce
      progressive aneurysm thrombosis without additional implants and may initiate
      complete reverse vessel remodeling. The associated vascular biologic processes
      are as yet only partially understood. MATERIALS AND METHODS: From 12 different
      centers, 13 cases of delayed postprocedural aneurysm rupture were recorded and
      analyzed. Symptom, aneurysm location and morphology, and the time elapsed from
      treatment until rupture were analyzed. RESULTS: There were 10 internal carotid
      and 3 basilar artery aneurysms. Mean aneurysm diameter was 22 +/- 6 mm. Eleven
      patients were symptomatic before treatment. A single FD was used for all saccular
      aneurysms, while fusiform lesions were treated by using multiple devices. A
      supplementary loose coiling of the aneurysm was performed in 1 patient only. Ten
      patients developed early aneurysm rupture after FD treatment (mean, 16 days;
      range, 2-48 days); in 3 patients, rupture occurred 3-5 months after treatment. In
      all cases, most of the aneurysm cavity was thrombosed before rupture. The
      biologic mechanisms predisposing to rupture under these conditions are reviewed
      and discussed CONCLUSIONS: FDs alone may modify hemodynamics in ways that induce
      extensive aneurysm thrombosis. Under specific conditions, however, instead of
      reverse remodeling and cicatrization, aggressive thrombus-associated autolysis of
      the aneurysm wall may result in delayed rupture.

PMID- 21071539
TI  - Generalizability and epidemiologic characterization of eleven colorectal cancer
      GWAS hits in multiple populations.
AB  - BACKGROUND: Genome-wide association studies (GWAS) in populations of European
      ancestry have identified several loci that confer an increased risk of colorectal
      cancer (CRC). METHODS: We studied the generalizability of the associations with
      11 risk variants for CRC on 8q23 (rs16892766), 8q24 (rs6983267), 9p24 (rs719725),
      10p14 (rs10795668), 11q23 (rs3802842), 14q22 (rs4444235), 15q13 (rs4779584),
      16q22 (rs9929218), 18q21 (rs4939827), 19q13 (rs10411210), and 20p12 (rs961253) in
      a multiethnic sample of 2,472 CRC cases, 839 adenoma cases and 4,466 controls
      comprised of European American, African American, Native Hawaiian, Japanese
      American, and Latino men and women. Because findings for CRC and adenoma were
      similar, we combined both groups in the analyses. RESULTS: We confirmed the
      associations with an increased risk of CRC/adenoma for the 8q24, 11q23 and 15q13
      loci in European Americans, and observed significant associations between the
      8q24 and 20p12 loci with CRC/adenoma risk in African Americans. Moreover, we
      found statistically significant cumulative effects of risk alleles on CRC/adenoma
      risk in all populations (odds ratio [OR] per allele = 1.07-1.09, P <= 0.039)
      except in Japanese Americans (OR = 1.01, P = 0.52). We found heterogeneity in the
      associations by tumor subsite, age of CRC/adenoma onset, sex, body mass index
      (BMI), and smoking status for some of the variants. CONCLUSIONS: These results
      provide evidence that the known variants are in aggregate significantly
      associated with CRC/adenoma risk in multiple populations except Japanese
      Americans, and the influences may differ across groups defined by
      clinicopathological characteristics for some variants. IMPACT: These results
      underline the importance of studying the epidemiologic architecture of these
      genetic effects in large and diverse populations.

PMID- 21071542
TI  - Differential gene expression analysis of Paracoccidioides brasiliensis during
      keratinocyte infection.
AB  - Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, one of the
      most important systemic fungal diseases in Latin America. This initiates in lung
      tissue and can subsequently disseminate to other tissues. Clinical manifestations
      range from localized forms to disseminated disease that can progress to
      lethality, probably depending on the relationships among the virulence of the
      fungus, the immune response and the ability to interact with the surface
      structures and invade epithelial cells and mononuclear cells of the host. It is
      generally regarded as a multifocal disease, with oral lesions as the prominent
      feature. The aim of this study was to evaluate P. brasiliensis yeast infection in
      normal oral keratinocytes (NOKs). The differential expression of mRNAs and
      proteins was also determined when the fungus was placed in contact with the cell
      in order to characterize differentially expressed genes and proteins during P.
      brasiliensis infection. After contact with NOKs, the fungus appeared to induce
      alterations in the cells, which showed cellular extensions and cavitations,
      probably resulting from changes in the actin cytoskeleton seen at 5 and
      8&emsp14;h after infection. Levels of protein expression were higher after
      reisolation of the fungus from infected NOK culture compared with culture of the
      fungus in medium. The analysis identified transcripts related to 19 proteins
      involved in different biological processes. Transcripts were found with multiple
      functions including induction of cytokines, protein metabolism, alternative
      carbon metabolism, zinc transport and the stress response during contact with
      NOKs. The proteins found suggested that the yeast was in a stress situation, as
      indicated by the presence of RDS1. Nevertheless, the yeast seemed to be
      proliferating and metabolically active, as shown by the presence of a proteasome,
      short-chain acetylator, glucosamine-6-phosphate isomerase and ADP/ATP carrier
      transcripts. Additionally, metabolic pathways may have been activated in order to
      eliminate toxic substances from the cell as a zinc transporter was detected,
      which is a potential target for the development of future drugs.

PMID- 21071541
TI  - Risk of cervical cancer associated with allergies and polymorphisms in genes in
      the chromosome 5 cytokine cluster.
AB  - BACKGROUND: Human papillomavirus is the acknowledged cause of cervical cancer. We
      hypothesized that allergies, characterized by hyperimmune reaction to common
      allergens and which have been associated with various cancers, may be related to
      cervical cancer, and that genetic variation in cytokine genes related to
      allergies might impact cervical cancer risk. METHODS: We investigated the risk of
      invasive squamous cell cervical cancer (SCC) associated with self-reported
      allergies and with variation in allergy-related cytokine genes using data from a
      case-control study (561 cases, 1,258 controls) conducted in Washington State.
      Logistic regression models yielded odds ratios (OR) and 95% CI. RESULTS: Pollen
      allergy, the most commonly reported allergy, was associated with reduced SCC risk
      (OR: 0.6; 95% CI: 0.5-0.8). Of 60 tagging single-nucleotide polymorphisms
      covering eight genes (CSF2, IL3, IL4, IL13, CSF2RB, IL4R, IL13RA1, IL13RA2),
      several were related to pollen allergies among controls: IL4R rs3024647 (dominant
      OR: 1.5; 95% CI: 1.0-2.3; P = 0.04), CSF2RB rs16997517 (dominant OR: 2.2; 95% CI:
      1.0-4.7; P = 0.04), and IL13 rs1800925 (per-allele OR: 1.7; 95% CI: 1.3-2.4; P =
      0.0007). Two variants were inversely associated with SCC risk: IL4R rs3024656
      (per-allele OR: 0.8; 95% CI: 0.6-1.0; P = 0.03) and CSF2RB rs16997517 (dominant
      OR: 0.4; 95% CI: 0.2-0.9; P = 0.04). CONCLUSIONS: Pollen allergies were related
      to reduced SCC risk. CSF2RB rs16997517 was directly related to pollen allergies
      in controls and to reduced SCC risk. IMPACT: If other studies confirm these
      results, the mechanism behind allergy-associated immune response associated with
      SCC risk may be worth exploring in the context of therapeutic or prophylactic
      vaccines.

PMID- 21071543
TI  - Serotype distribution and antimicrobial resistance patterns of Streptococcus
      pneumoniae isolated in Tunisia.

PMID- 21071540
TI  - Validation of genome-wide prostate cancer associations in men of African descent.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified numerous
      prostate cancer susceptibility alleles, but these loci have been identified
      primarily in men of European descent. There is limited information about the role
      of these loci in men of African descent. METHODS: We identified 7,788 prostate
      cancer cases and controls with genotype data for 47 GWAS-identified loci.
      RESULTS: We identified significant associations for SNP rs10486567 at JAZF1,
      rs10993994 at MSMB, rs12418451 and rs7931342 at 11q13, and rs5945572 and
      rs5945619 at NUDT10/11. These associations were in the same direction and of
      similar magnitude as those reported in men of European descent. Significance was
      attained at all reported prostate cancer susceptibility regions at chromosome
      8q24, including associations reaching genome-wide significance in region 2.
      CONCLUSION: We have validated in men of African descent the associations at some,
      but not all, prostate cancer susceptibility loci originally identified in
      European descent populations. This may be due to the heterogeneity in genetic
      etiology or in the pattern of genetic variation across populations. IMPACT: The
      genetic etiology of prostate cancer in men of African descent differs from that
      of men of European descent.

PMID- 21071544
TI  - Simultaneous carriage of multiple genotypes of Staphylococcus aureus in children.
AB  - The co-existence of multiple genotypes in colonization by Staphylococcus aureus
      has not been fully investigated. The aim of this study was to evaluate the
      heterogeneity of S. aureus carriage in children. We evaluated 125 nasal and
      perianal swab samples that were positive for S. aureus from 76 children scheduled
      for elective surgery. For each sample, at least four colonies with the same or
      different morphotypes were selected for analysis. Multiple-locus variable-number
      tandem-repeat fingerprinting was used to determine the genetic relatedness and to
      characterize the clonality of the S. aureus strains. Of the 125 swabs, 91 (73 %)
      contained meticillin-sensitive S. aureus (MSSA), 8 (6 %) contained meticillin
      resistant S. aureus (MRSA), and 26 (21 %) contained MSSA and MRSA simultaneously.
      A total of 738 S. aureus strains were evaluated with a mean of 6 colonies (range
      4-15) picked from each culture. Of the 125 swabs, 32 (26 %) samples contained two
      genetically distinct S. aureus strains and 6 (5 %) contained three different
      genotypes. Multiple S. aureus strains simultaneously carried by individual
      children were genetically unrelated to each other. We concluded that the co
      existence of multiple genotypes of S. aureus was common. The significance of
      multiple carriage is yet to be determined, but this intraspecies interplay could
      be important to pathogenicity and virulence in S. aureus.

PMID- 21071545
TI  - Risk factors for Pneumocystis jiroveci pneumonia (PcP) in renal transplant
      recipients.
AB  - BACKGROUND: Pneumocystis jiroveci pneumonia (PcP) is a potentially life
      threatening complication in renal transplant recipients with increased reports
      during the past few years. Individual risk factors for susceptibility to PcP are
      incompletely understood. METHODS: We retrospectively analysed 60 cases of
      confirmed PcP, diagnosed in six German transplant centres between 2004 and 2008,
      as well as 60 matched controls. RESULTS: Compared with controls, PcP cases
      revealed the following significant differences: PcP cases had a poorer renal
      function (eGFR 31 vs. 42 mL/min in controls), more biopsy-proven rejections (18
      vs. 5 patients), more frequent treatment with mycophenolate mofetil (53 vs. 44
      patients) and less frequent treatment with interleukin-2 receptor antagonist (20
      vs. 32 patients). According to centre policy, in those years, none of the
      patients or controls had received PcP prophylaxis after transplantation. Of the
      60 patients with PcP, 30% developed the disease after the currently recommended
      duration of prophylactic treatment, 27% died in the course of the disease and 45%
      required treatment in the ICU. CONCLUSIONS: Our case-control study reveals a
      novel risk profile for PcP. Renal transplant recipients with more pronounced
      renal insufficiency following rejection episodes and treated with intensified
      immunosuppression are at particular risk for PcP.

PMID- 21071546
TI  - Dedication of a nurse to educating suboptimal haemodialysis starts improved
      transition to independent modalities of renal replacement therapy.
AB  - BACKGROUND: Haemodialysis (HD) initiation is unplanned in up to 50% of patients,
      mainly due to late diagnosis and/or late nephrology referral. In these patients,
      time does not permit the multidisciplinary predialysis care that is associated
      with increased independent renal replacement therapy (RRT) modality choice and
      better access to kidney transplantation. We established a Renal Triage Nurse
      (RTN) position to educate suboptimal HD starts and to facilitate transition to
      independent modalities of RRT. METHODS: Adult patients starting HD from 1 January
      2005 to 31 December 2008 with < 180 days nephrology follow-up and surviving at
      least 180 days were included (suboptimal HD starts). The RTN educated suboptimal
      HD starts beginning in December 2006. Patients initiating RRT via the
      multidisciplinary predialysis clinic (MPC) were included for comparison.
      Multivariable logistic regression was used to determine the association between
      being seen by the RTN and achieving independent modalities of RRT. RESULTS: There
      were 176 patients: 78 suboptimal HD starts (38 of these were educated by the RTN)
      and 98 patients initiated RRT after a minimum 180-day follow-up at the MPC. Of
      the RTN patients, 27.8% switched to independent RRT modalities (peritoneal
      dialysis n = 7, home haemodialysis n = 1, transplant n = 2). RTN patients were
      more likely to live alone (33.3% versus 10.8%, P = 0.02) and to have
      cerebrovascular disease (25.0% versus 7.1%, P = 0.03); however, adjusting for
      these variables, suboptimal HD starts seen by the RTN were more likely to
      transition to independent RRT (OR 3.75, 95% CI 1.08-13.05) than those not seen.
      The proportion starting on an independent modality via the MPC was 39.8%. The RTN
      achieved a rate of independent RRT not statistically different to that observed
      in patients starting RRT via the MPC (OR 0.74, 95% CI 0.19-2.94 in multivariable
      analysis). CONCLUSIONS: Addition of the RTN to the HD care team facilitated
      transition to independent modalities of RRT in suboptimal HD starts. This
      standardized approach to the care of such patients should be considered in HD
      units where suboptimal HD starts are common.

PMID- 21071547
TI  - A systematic assessment of causes of death after heart failure onset in the
      community: impact of age at death, time period, and left ventricular systolic
      dysfunction.
AB  - BACKGROUND: The high mortality rate in patients with heart failure (HF) is
      influenced by presence of multiple comorbidities. Data are limited on the
      relative contributions of cardiovascular versus noncardiovascular diseases to
      death in individuals with HF in the community. METHODS AND RESULTS: We examined
      the incidence and predictors of cardiovascular versus noncardiovascular death in
      participants with HF in the Framingham Heart Study. Underlying, immediate, and
      contributing causes of death (3 key elements of the World Health Organization
      classification) were adjudicated by a 3-physician review panel. During 1971 to
      2004, 1025 participants with HF died (499 men, mean [SD] age at death 79 [11]
      years), including 463 participants with left ventricular ejection fraction (LVEF)
      data. Cardiovascular disease was the cause of death in 66.1% overall. Stratified
      by LVEF, cardiovascular deaths occurred in 44.5% and 69.9% of those with
      preserved and reduced LVEF, respectively. Presence of reduced LVEF increased the
      risk of cardiovascular death, with odds ratios of 3.16 (95% confidence interval
      [CI], 1.73 to 5.78) in men and 2.39 (95% CI, 1.39 to 4.08) in women. Prior
      myocardial infarction was associated with increased cardiovascular death in women
      with HF (odds ratio, 1.87; 95% CI, 1.10 to 3.16) but not in men. The risk of
      cardiovascular disease death decreased in women (odds ratio after 1980, 0.41; 95%
      CI, 0.24 to 0.69) and men (odds ratio, 0.66; 95% CI, 0.41 to 1.07, P=0.095) with
      HF over time. Infections and kidney disease emerged as key immediate and
      contributing causes of death, respectively. CONCLUSIONS: Individuals with HF in
      the community often experience cardiovascular death, but noncardiovascular
      disease also contributes significantly especially among those with preserved
      LVEF.

PMID- 21071548
TI  - Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.
AB  - The purpose of the present study was to characterize the genetic damage induced
      by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy
      (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using
      the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the
      platform technique for 72 hours, followed by drug administration and evaluation
      of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to
      induce genetic damage in the blood, brain and liver cells of sleep-deprived mice
      at the majority of the doses evaluated. Ecstasy also induced increased DNA
      migration in peripheral blood cells for all concentrations tested. Analysis of
      damaged cells by the tail moment data suggests that ecstasy is a genotoxic
      chemical at the highest concentrations tested, inducing damage in liver or brain
      cells after sleep deprivation in mice. Taken together, our results suggest that
      cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when
      associated with sleep loss.

PMID- 21071549
TI  - Delayed toxic effects of sulfur mustard on respiratory tract of Iranian veterans.
AB  - To investigate late toxic effects of sulfur mustard (SM) on the upper and lower
      respiratory tracts of Iranian veterans, 43 male veterans with more than 25%
      disability due to SM poisoning in 20-25 years after exposure, were studied.
      Direct laryngoscopy, pulmonary function tests, arterial blood gasses and pH,
      computed tomography of sinuses and lungs were investigated. The patients were
      aged 50.6 (8.9 SD) years with body mass index (BMI) of 26.6 (4.0) and disability
      of 53.2 (17.0%). The common findings of the upper respiratory tract were
      dysphonia (79.1%), post-nasal discharge (PND; 41.9%), lower larynx position
      (30.2%), limitation of vocal cords (25.6%) and mucosal inflammation of larynx
      (14.8%). The common lower respiratory diseases were diagnosed as chronic
      obstructive respiratory disease (84%), bronchiectasis (44.1%) and lung fibrosis
      (7.7%). Severity of disability was negatively correlated with BMI (p = 0.032),
      spirometric parameters (p < 0.001) and oxygen saturation (p < 0.001), but
      positively correlated with low-density lipoproteins (LDL <0.010), blood pressure
      (p = 0.008), diabetes mellitus (p < 0.001), wheezing (p = 0.0043) and
      bronchiectasis (p < 0.001). Delayed toxic effects of SM in upper and lower
      respiratory tracts were mostly inflammatory and infectious complications, SM
      induced disabilities were significantly correlated with risk factors such as
      diabetes mellitus, hypertension, LDL and lower-respiratory complications.

PMID- 21071550
TI  - Toxic influence of organophosphate, carbamate, and organochlorine pesticides on
      cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.
AB  - Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate
      (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB
      act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as
      peripheral and central nervous systems, muscles, liver, pancreas, and brain,
      whereas OC are neurotoxic involved in alteration of ion channels. There are
      several reports about metabolic disorders, hyperglycemia, and also oxidative
      stress in acute and chronic exposures to pesticides that are linked with diabetes
      and other metabolic disorders. In this respect, there are several in vitro and in
      vivo but few clinical studies about mechanism underlying these effects.
      Bibliographic databases were searched for the years 1963-2010 and resulted in
      1652 articles. After elimination of duplicates or irrelevant papers, 204 papers
      were included and reviewed. Results indicated that OP and CB impair the enzymatic
      pathways involved in metabolism of carbohydrates, fats and protein within
      cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this
      effect through inhibition of AChE or affecting target organs directly. OC mostly
      affect lipid metabolism in the adipose tissues and change glucose pathway in
      other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative
      stress via affecting mitochondrial function and therefore disrupt neuronal and
      hormonal status of the body. Establishing proper epidemiological studies to
      explore exact relationships between exposure levels to these pesticides and rate
      of resulted metabolic disorders in human will be helpful.

PMID- 21071551
TI  - The World Library of Toxicology, Chemical Safety, and Environmental Health (WLT).
AB  - The World Library of Toxicology, Chemical Safety, and Environmental Health,
      commonly referred to as the World Library of Toxicology (WLT), is a multilingual
      online portal of links to key global resources, representing a host of individual
      countries and multilateral organizations. The Site is designed as a network of,
      and gateway to, toxicological information and activities from around the world.
      It is built on a Wiki platform by a roster of Country Correspondents, with the
      aim of efficiently exchanging information and stimulating collaboration among
      colleagues, and building capacity, with the ultimate objective of serving as a
      tool to help improve global public health. The WLT was publicly launched on
      September 7, 2009, at the Seventh Congress of Toxicology in Developing Countries
      (CTDC-VII) in Sun City, South Africa.

PMID- 21071552
TI  - A traditional formula, Chunggan extract, attenuates thioacetamide-induced
      hepatofibrosis via GSH system in rats.
AB  - Chunggan extract (CGX) is a hepatotherapeutic herbal formula which has been
      traditionally used for patients suffering from various hepatic disorders. This
      study aimed to elucidate antifibrotic effect and mechanisms of CGX in
      thioacetamide (TAA) model. Hepatic fibrosis was induced in 45 Sprague-Dawley rats
      by TAA (200 mg kg(-1), intraperitoneally [ip]) on twice per week for 12 weeks.
      CGX (100 or 200 mg kg(-1), per oral [po]) was administrated once a day throughout
      the experiment. CGX treatment ameliorated serum biomarkers. CGX administration
      significantly attenuated distortion of histopathologic finding, and accumulation
      of hydroxyproline and malondialdehyde (MDA). CGX treatment significantly
      decreased transforming growth factor-beta (TGF-beta) concentrations and
      inactivated hepatic stellate cells (HSCs). CGX treatment drastically restored
      glutathione (GSH) system, while inducible nitric oxide synthase (iNOS) and tumor
      necrosis factor-alpha (TNF-alpha) significantly down-regulated in liver tissue.
      CGX showed antifibrotic effect in thioacetamide-induced chronic liver injury
      model. Its corresponding mechanisms may be mediated via anti-oxidative stress
      property sustaining GSH system and inhibition of ROS production.

PMID- 21071553
TI  - Chemosensory irritations and pulmonary effects of acute exposure to emissions
      from oriented strand board.
AB  - Due to the reduction of air change rates in low-energy houses, the contribution
      to indoor air quality of volatile organic compounds (VOCs) emitting from oriented
      strand boards (OSB) has become increasingly important. The aim of this study was
      to evaluate sensory irritations, pulmonary effects and odor annoyance of
      emissions from OSB in healthy human volunteers compared to clean air. Twenty-four
      healthy non-smokers were exposed to clean air and OSB emissions for 2 h under
      controlled conditions in a 48 m(3) test chamber at three different time points:
      to fresh OSB panels and to the same panels after open storage for 2 and 8 weeks.
      Chemosensory irritation, exhaled nitric oxide (NO) concentration, eye blink
      frequency, lung function and subjective perception of irritation of eyes, nose
      and throat were examined before, during and after exposure. Additionally,
      olfactory perception was investigated. Total VOC exposure concentrations reached
      8.9 +/- 0.8 mg/m(3) for the fresh OSB panels. Emissions consisted predominantly
      of alpha-pinene, Delta(3)-carene and hexanal. Two-hour exposure to high VOC
      concentrations revealed no irritating or pulmonary effects. All the subjective
      ratings of discomfort were at a low level and the medians did not exceed the
      expression 'hardly at all.' Only the ratings for smell of emissions increased
      significantly during exposure in comparison to clean air. In conclusion, exposure
      of healthy volunteers to OSB emissions did not elicit sensory irritations or
      pulmonary effects up to a VOC concentration of about 9 mg/m(3). Sensory intensity
      of OSB emissions in the chamber air was rated as 'neutral to pleasant.'

PMID- 21071554
TI  - Leucocytes DNA damage in mice exposed to JS-118 by the comet assay.
AB  - JS-118 is an extensively used insecticide in China. The present study
      investigated the genotoxic effect of JS-118 on whole blood at 24, 48, 72 and 96 h
      by using alkaline comet assay. Male Kunming mice were given 6.25, 12.5, 25, 50
      and 100 mg/kg BW of JS-118 intraperitoneally. A statistically significant
      increase in all comet parameters indicating DNA damage was observed at 24 h post
      treatment (p < 0.05). A clear concentration-dependent increase of DNA damage was
      revealed as evident by the OTM (arbitrary units), tail length (um) and tail DNA
      (%). From 48 h post-treatment, a gradual decrease in mean comet parameters was
      noted. By 96 h of post-treatment, the mean comet tail length reached control
      levels indicating repair of damaged DNA. This study on mice showed different DNA
      damage depending on the concentration of JS-118 and the period of treatment. The
      present study provided further information of the potential risk of the genetic
      damage caused by JS-118.

PMID- 21071555
TI  - Decreased antioxidase activities and oxidative stress in the spleen of chickens
      fed on high-fluorine diets.
AB  - Three hundred one-day-old avian broilers were divided into four equal groups of
      75 animals that were fed for 42 days as follows: a control diet containing 23 mg
      fluorine (F)/kg and three high F diets containing 400, 800, and 1200 mg F/kg,
      respectively, for high F groups I, II, and III. The superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-Px) activities were greatly decreased, while the
      malondialdehyde (MDA) contents were markedly increased in high F groups II and
      III. At the same time, mitochondrial injury and expanded endocytoplasmic
      reticulum were obviously observed in high F groups II and III, and the fluoride
      contents both in spleen and serum were significantly increased in the three high
      F groups when compared with those of control group. The results showed that
      excess dietary F in the range of 800-1200 mg/kg caused obvious oxidative stress,
      which provided a possible pathway for the apoptosis of splenocytes in chickens.

PMID- 21071557
TI  - What is an emergency?

PMID- 21071556
TI  - {Beta}2-adrenergic receptor agonists inhibit the proliferation of 1321N1
      astrocytoma cells.
AB  - Astrocytomas and glioblastomas have been particularly difficult to treat and
      refractory to chemotherapy. However, significant evidence has been presented that
      demonstrates a decrease in astrocytoma cell proliferation subsequent to an
      increase in cAMP levels. The 1321N1 astrocytoma cell line, as well as other
      astrocytomas and glioblastomas, expresses beta(2)-adrenergic receptors (beta(2)
      ARs) that are coupled to G(s) activation and consequent cAMP production.
      Experiments were conducted to determine whether the beta(2)-AR agonist (R,R')
      fenoterol and other beta(2)-AR agonists could attenuate mitogenesis and, if so,
      by what mechanism. Receptor binding studies were conducted to characterize
      beta(2)-AR found in 1321N1 and U118 cell membranes. In addition, cells were
      incubated with (R,R')-fenoterol and analogs to determine their ability to
      stimulate intracellular cAMP accumulation and inhibit [(3)H]thymidine
      incorporation into the cells. 1321N1 cells contain significant levels of beta(2)
      AR as determined by receptor binding. (R,R')-fenoterol and other beta(2)-AR
      agonists, as well as forskolin, stimulated cAMP accumulation in a dose-dependent
      manner. Accumulation of cAMP induced a decrease in [(3)H]thymidine incorporation.
      There was a correlation between concentration required to stimulate cAMP
      accumulation and inhibit [(3)H]thymidine incorporation. U118 cells have a reduced
      number of beta(2)-ARs and a concomitant reduction in the ability of beta(2)-AR
      agonists to inhibit cell proliferation. These studies demonstrate the efficacy of
      beta(2)-AR agonists for inhibition of growth of the astrocytoma cell lines.
      Because a significant portion of brain tumors contain beta(2)-ARs to a greater
      extent than whole brain, (R,R')-fenoterol, or some analog, may be useful in the
      treatment of brain tumors after biopsy to determine beta(2)-AR expression.

PMID- 21071559
TI  - Can cardiac [123I]m-iodobenzylguanidine imaging be used for risk stratification
      of patients with acute myocardial infarction?

PMID- 21071560
TI  - Income, income, or income? The effects of different income measures on health in
      a national survey.
AB  - BACKGROUND: The effects of six income types (household post-government income,
      Organisation for Economic Cooperation and Development-weighted household post
      government income, individual net income, corrected monthly household income and
      household net income from wages) on subjective health were compared in order to
      examine to what extent their effects are different. METHODS: Data from the German
      Socio-Economic Panel 2007 were used. The analyses were based on the subsample of
      30-60-year-old women and men (N=11,471), incomes were divided into 10 groups of
      equal size. In addition education, gender and age are considered. RESULTS: The
      effects of the household incomes were similar by ranging from OR 3.1 to 3.7. For
      individual income the effect was lower (OR 2.1). This has to be interpreted
      against the backdrop of a large number of subjects with missing income
      information. This group consists of not employed, unemployed and retired
      individuals. CONCLUSION: The five types of household incomes can be considered as
      interchangeable with respect to their effects on subjective health. In empirical
      studies household-based measures are appropriate if material resources or the
      purchasing power of households are depicted. Individual income is a different
      measure that should be chosen if the individual position in terms of status or
      material success is to be measured.

PMID- 21071558
TI  - Short- and long-term effects of erythropoietin treatment on endothelial
      progenitor cell levels in patients with cardiorenal syndrome.
AB  - OBJECTIVE: Patients with cardiorenal syndrome (CRS) have high cardiovascular
      morbidity. Endothelial progenitor cells (EPC) constitute an endogenous vascular
      repairsystem, protecting against atherosclerosis development. Erythropoietin
      (EPO) treatment may have beneficial effects by mobilizing EPC from the
      bonemarrow. Our objective is to determine EPC levels and effects of EPO therapy
      on EPC levels in CRS patients. DESIGN: Open-label randomized trial. SETTING: Part
      of the EPOCARES-trial, conducted in Utrecht (Netherlands). PATIENTS: Patients
      with CRS and anaemia and healthy controls were included. Interventions Patients
      were randomized to receive EPO therapy (50 IU/kg/wk) for 52 weeks or no EPO
      therapy. MAIN OUTCOME MEASURES: CD34(+)KDR(+)-EPC, cultured EPC outgrowth and
      function at baseline, after 18 days and after 52 weeks. RESULTS: Patients showed
      lower CD34(+)KDR(+)-cell numbers compared to controls (6(12) vs. 19(19)
      cells/10(5) granulocytes; p = 0.010), despite increased levels of stromal cell
      derived factor-1alpha; (3.1(0.8) vs 2.6(0.3) ng/ml; p = 0.001). EPC outgrowth and
      function were not different between patients and controls. EPC levels did not
      change after 18&emsp14;days with or without EPO treatment. CD34(+)KDR(+)-cells
      significantly declined after 52 weeks in the non-treated group (p = 0.028). Long
      term EPO therapy did not significantly affect this reduction in CD34(+)KDR(+)-EPC
      levels. CONCLUSIONS: CRS patients showed reduced CD34(+)KDR(+)-EPC levels
      compared to controls, consistent with a reduced vascular regenerative potential
      and despite upregulated SDF-1alpha levels. Over a one-year follow-up period a
      marked 68% further reduction in EPC levels was observed in the patient group
      without EPO treatment. In spite of promising experimental studies, our
      longitudinal, randomized study did not show significant influence of either short
      or long-term EPO therapy on reduced EPC levels in CRS patients.

PMID- 21071561
TI  - Effects of Smokefree Class Competition 1 year after the end of intervention: a
      cluster randomised controlled trial.
AB  - BACKGROUND: The Smokefree Class Competition, a school-based smoking prevention
      intervention, is widely disseminated in Europe. Participating classes commit
      themselves to be smoke-free and self-monitor their smoking status. Classes that
      remain smoke-free for 6 months can win prizes. Effects of the intervention on
      current smoking, initiation and progression of smoking were investigated.
      METHODS: Cluster randomised controlled trial. 84 schools (208 classes with 3490
      students; mean age 12.6 years, 50.4% female) in Saxony-Anhalt, Germany, were
      randomly assigned to intervention or control condition. A baseline survey was
      conducted before the implementation of the programme, while post-test and follow
      up surveys were carried out 7 (immediately after the end of the competition), 12
      and 19 months after baseline. Effects of participation in the programme on
      current and lifetime smoking were analysed by multilevel models controlling for
      confounding variables. RESULTS: Intervention students smoking occasionally at
      baseline smoked less frequently than students taking not part in the intervention
      at 7 and 12 months after baseline. Persistent beneficial programme effects were
      also found for lifetime smoking: intervention students were less likely to
      progress from experimental to established use. CONCLUSION: Data suggest that
      Smokefree Class Competition reduces the probability of progressing from
      occasional and experimental stages of smoking to more established forms of use.
      CLINICAL TRIALS REGISTRATION NUMBER: Trial registration ISRCTN27091233 in Current
      Control Trial Register.

PMID- 21071563
TI  - HIV-related sexual risk behaviour between 1996 and 2008, according to age, among
      men who have sex with men (Scotland).
AB  - OBJECTIVE: To examine changes in the proportions of those reporting 2+
      unprotected anal intercourse (UAI) partners in the previous 12 months among men
      who have sex with men (MSM) in Scotland between 1996 and 2008. Differences
      according to age group were also examined. METHODS: Logistic regression was used
      with data from eight cross-sectional anonymous, self-report surveys in commercial
      gay venues in Glasgow and Edinburgh (N=10,223). Data were stratified according to
      survey and age group (<25 years vs >=25 years). RESULTS: The percentage of 2+ UAI
      partners reported in the previous 12 months increased significantly between 2000
      and 2002, adjusted for age group. When the surveys were divided into two time
      periods (1996-2000 and 2002-2008), no significant differences were found within
      each time period in the percentage of 2+ UAI partners reported (adjusted for age
      group). However, a significant increase was found when the aggregated figures for
      2002-2008 were compared with those for 1996-2000. At the aggregate level, those
      aged <25 years were significantly more likely than those aged >=25 years to
      report 2+ UAI partners in the previous 12 months (adjusted for survey).
      CONCLUSIONS: HIV-related sexual risk behaviour did not change significantly
      between 2002 and 2008 among MSM in Scotland, after the increases noted between
      2000 and 2002. A significant minority of MSM continue to engage in relatively
      high levels of sexual risk, and younger generations appear to be at particular
      risk. This represents a public health concern and highlights the need for
      targeted age-specific interventions.

PMID- 21071562
TI  - Social environment and asthma: associations with crime and No Child Left Behind
      programmes.
AB  - BACKGROUND: The relationship between asthma and socio-economic status remains
      unclear. The authors investigated how neighbourhood, school and community social
      environments were associated with incident asthma in Southern California
      schoolchildren. METHODS: New-onset asthma was measured over 3 years of follow-up
      in the Children's Health Study cohort. Multilevel random-effects models assessed
      associations between social environments and asthma, adjusted for individual risk
      factors. At baseline, subjects resided in 274 census tracts (ie, neighbourhoods)
      and attended kindergarten or first grade in one of 45 schools distributed in 13
      communities throughout Southern California. Neighbourhoods and communities were
      characterised by measures of deprivation, income inequality and racial
      segregation. Communities were further described by crime rates. Information on
      schools included whether a school received funding related to the Title 1 No
      Child Left Behind programme, which aims to reduce academic underachievement in
      disadvantaged populations. RESULTS: Increased risk for asthma was observed in
      subjects attending schools receiving Title I funds compared with those from
      schools without funding (adjusted HR 1.71, 95% CI 1.14 to 2.58), and residing in
      communities with higher rates of larceny crime (adjusted HR 2.02, 95% CI 1.08 to
      3.02 across the range of 1827 incidents per 100,000 population). CONCLUSIONS:
      Risk for asthma was higher in areas of low socio-economic status, possibly due to
      unmeasured risk factors or chronic stress.

PMID- 21071564
TI  - Syphilitic periostitis of the skull and ribs in a HIV positive patient.
AB  - We report the case of a HIV and syphilis co-infected patient who presented with
      headache and rash and was found to have syphilitic periostitis. Our case
      illustrates a rare manifestation of early syphilis and presents the diagnostic
      dilemmas that can arise in HIV and syphilis co-infected patients.

PMID- 21071565
TI  - Comparison of users of an HIV/syphilis screening community-based mobile van and
      traditional voluntary counselling and testing sites in Guatemala.
AB  - OBJECTIVES: The use of a mobile van (MV) for screening for HIV and other sexually
      transmitted infections (STIs) is effective at reaching at-risk populations. The
      aim of this study was to compare behaviour characteristics and HIV and syphilis
      prevalence between subjects tested at a MV offering voluntary counselling and
      testing and those tested at three STI clinics in Guatemala. METHODS: Over 28
      months, female sex workers (FSWs), men who have sex with men/transgenders
      (MSM/TG), and people not reporting being a member of a risk group (NR) were
      offered HIV and syphilis rapid tests and interviewed about their sociodemographic
      and risk behaviour. RESULTS: 2874 subjects were tested (MV, 1336 (46%); clinics,
      1538 (54%)). The MV screened 73% of FSWs and 73% of the MSM/TG, and detected 19%
      of HIV and 69% of syphilis cases. HIV prevalence was significantly higher
      (p<0.001) at the STI clinics than at the MV for both NR and MSM/TG groups (NR, 7%
      vs 1%; MSM/TG, 8% vs 1%, respectively). A significantly higher proportion of
      MSM/TG screened at the STI clinic reported having had a prior HIV test (MV, 21%;
      clinics, 41%; p<0.001), whereas more FSWs tested in the MV reported having
      multiple partners and using condoms during their last sexual intercourse.
      CONCLUSIONS: The higher prevalence of HIV and syphilis at the STI clinics
      suggests that they successfully identified high-risk subjects. In particular, the
      NR group showed higher than expected HIV and syphilis prevalence. Innovative
      approaches such as the use of a MV helped to increase access to other hard-to
      reach groups such as MSM/TG and FSWs.

PMID- 21071566
TI  - Mycoplasma genitalium is associated with cervicitis and HIV infection in an urban
      Australian STI clinic population.
AB  - OBJECTIVES: To investigate the prevalence of the genital mollicutes, Mycoplasma
      genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and
      Ureaplasma parvum (UP), and their associations with cervicitis in a sexually
      transmitted infection (STI) clinic population. Clinical correlates of MG
      infection were also assessed. METHODS: 527 women were enrolled in a cross
      sectional study at two STI clinics in Sydney between June 2006 and January 2010.
      Genital mollicutes were detected by multiplex PCR testing of cervical swabs, and
      associations with cervicitis were analysed. Cervicitis was defined as >30
      polymorphonuclear cells per high-power field in at least three non-adjacent
      fields of cervical mucus on Gram stain. RESULTS: MG was found in 4.0% of women,
      MH in 17.1%, UU in 14.1%, and UP in 51.8%. MG was the only mollicute associated
      with cervicitis (unadjusted prevalence ratio (PR) 1.85, 95% CI 1.52 to 2.26,
      p<0.0001), and this association remained after adjustment for Chlamydia
      trachomatis (CT) infection (adjusted PR 1.24 (95% CI 1.04 to 1.48), p=0.02). MG
      was significantly associated with women being HIV positive (p=0.03), but not with
      age, vaginal discharge, commercial sex work, being of culturally and
      linguistically diverse background, or concurrent CT infection. Two of the 21
      women with MG had ectopic pregnancies. CONCLUSIONS: The authors recommend wider
      application of PCR testing for MG in STI services, particularly in high-risk
      women and those with cervicitis or HIV infection.

PMID- 21071567
TI  - Ethical challenges in fetal surgery.
AB  - Fetal surgery has been practised for some decades now. However, it remains a
      highly complex area, both medically and ethically. This paper shows how the
      routine use of ultrasound has been a catalyst for fetal surgery, in creating new
      needs and new incentives for intervention. Some of the needs met by fetal surgery
      are those of parents and clinicians who experience stress while waiting for the
      birth of a fetus with known anomalies. The paper suggests that the role of
      technology and visualisation techniques in creating and meeting such new needs is
      ethically problematic. It then addresses the idea that fetal surgery should be
      restricted to interventions that are life-saving for the fetus, arguing that this
      restriction is unduly paternalistic. Fetal surgery poses challenges for an
      autonomy-based system of ethics. However, it is risky to circumvent these
      challenges by restricting the choices open to pregnant women, even when these
      choices appear excessively altruistic.

PMID- 21071568
TI  - Legal physician-assisted suicide in Oregon and The Netherlands: evidence
      concerning the impact on patients in vulnerable groups--another perspective on
      Oregon's data.
AB  - Battin et al examined data on deaths from physician-assisted suicide (PAS) in
      Oregon and on PAS and voluntary euthanasia (VE) in The Netherlands. This paper
      reviews the methodology used in their examination and questions the conclusions
      drawn from it-namely, that there is for the most part 'no evidence of heightened
      risk' to vulnerable people from the legalisation of PAS or VE. This critique
      focuses on the evidence about PAS in Oregon. It suggests that vulnerability to
      PAS cannot be categorised simply by reference to race, gender or other
      socioeconomic status and that the impetus to seek PAS derives from factors,
      including emotional state, reactions to loss, personality type and situation and
      possibly to PAS contagion, all factors that apply across the social spectrum. It
      also argues, on the basis of official reports from the Oregon Health Department
      on the working of the Oregon Death with Dignity Act since 2008, that, contrary to
      the conclusions drawn by Battin et al, the highest resort to PAS in Oregon is
      among the elderly and, on the basis of research published since Battin et al
      reported, that there is reason to believe that some terminally ill patients in
      Oregon are taking their own lives with lethal drugs supplied by doctors despite
      having had depression at the time when they were assessed and cleared for PAS.

PMID- 21071569
TI  - Ethics of modifying the mitochondrial genome.
AB  - Recent preclinical studies have shown the feasibility of specific variants of
      nuclear transfer to prevent mitochondrial DNA disorders. Nuclear transfer could
      be a valuable reproductive option for carriers of mitochondrial mutations. A
      clinical application of nuclear transfer, however, would entail germ-line
      modification, more specifically a germ-line modification of the mitochondrial
      genome. One of the most prominent objections against germ-line modification is
      the fear that it would become possible to alter 'essential characteristics' of a
      future person, thereby possibly violating the child's right to an open future. As
      only the nuclear DNA would contain the ingredients for individual
      characteristics, modification of the mtDNA is often considered less controversial
      than modification of the nuclear DNA. This paper discusses the tenability of this
      dichotomy. After having clarified the concept of germ-line modification, it
      argues that modification of the mtDNA is not substantively different from
      modification of the nuclear DNA in terms of its effects on the identity of the
      future person. Subsequently the paper assesses how this conclusion affects the
      moral evaluation of nuclear transfer to prevent mtDNA disorders. It concludes
      that the moral acceptability of germ-line modification does not depend on whether
      it alters the identity of the future child-all germ-line modifications do-but on
      whether it safeguards the child's right to an open future. If nuclear transfer to
      prevent mtDNA disorders becomes safe and effective, then dismissing it because it
      involves germ-line modification is unjustified.

PMID- 21071570
TI  - Public attitudes to the use in research of personal health information from
      general practitioners' records: a survey of the Irish general public.
AB  - INTRODUCTION: Understanding the views of the public is essential if generally
      acceptable policies are to be devised that balance research access to general
      practice patient records with protection of patients' privacy. However, few large
      studies have been conducted about public attitudes to research access to personal
      health information. METHODS: A mixed methods study was performed. Informed by
      focus groups and literature review, a questionnaire was designed which assessed
      attitudes to research access to personal health information and factors that
      influence these. A postal survey was conducted of an electoral roll-based sample
      of the adult population of Ireland. RESULTS: Completed questionnaires were
      returned by 1575 (40.6%). Among the respondents, 67.5% were unwilling to allow
      GPs to decide when researchers could access identifiable personal health
      information. However, 89.5% said they would agree to ongoing consent
      arrangements, allowing the sharing by GPs of anonymous personal health
      information with researchers without the need for consent on a study-by-study
      basis. Increasing age (by each 10-year increment), being retired and primary
      level education only were significantly associated with an increased likelihood
      of agreeing that any personal health information could be shared on an ongoing
      basis: OR 1.39 (95% CI 1.18 to 1.63), 2.00 (95% CI 1.22 to 3.29) and 3.91 (95% CI
      1.95 to 7.85), respectively. CONCLUSIONS: Although survey data can be prone to
      response biases, this study suggests that prior consent agreements allowing the
      supply by GPs of anonymous personal health information to researchers may be
      widely supported, and that populations willing to opt in to such arrangements may
      be sufficiently representative to facilitate valid and robust consent-dependent
      observational research.

PMID- 21071571
TI  - Health service research: the square peg in human subjects protection regulations.
AB  - Protection of human participants is a fundamental facet of biomedical research.
      We report the activities of a health service research study in which there were
      three institutional review boards (IRBs), three legal departments and one
      research administration department providing recommendations and mandating
      changes in the study methods. Complying with IRB requirements can be challenging,
      but can also adversely affect study outcomes. Multiple protocol changes mandated
      from multiple IRBs created a research method that was not reflective of how
      substance use screening would be performed in a clinical setting. There was
      direct conflict between the IRBs' perceptions of participants' protection with
      the researchers' need to use research methodology that assures the clinical
      relevancy of results.

PMID- 21071573
TI  - Co-operative interactions between first- and second-order mechanisms in the
      processing of structure from motion.
AB  - Structure from motion (SFM) is the ability to perceive three-dimensional
      structure from stimuli containing only two-dimensional motion signals and this
      ability seems to be a result of high-level cortical processes. It has long been
      thought that local motion signals defined by second-order cues only weakly
      contribute to perception of SFM since performance on purely second-order SFM
      tasks is poor, relative to first-order stimuli. We hypothesized that the
      mechanisms responsible for deriving SFM were insensitive to low-level stimulus
      attributes such as the first- or second-order nature of the dots composing the
      stimulus, in other words: that they were "cue-invariant", but that large
      differences in sensitivity to local first- and second-order motions were
      responsible for previous findings. By manipulating the relative strength of first
      order dots in an SFM stimulus that combines first- and second-order dots, we show
      that the two types of motion can separately support SFM and co-operatively
      interact to produce vivid three-dimensional percepts. This provides strong
      support that the mechanisms underlying SFM are cue-invariant.

PMID- 21071574
TI  - The default allocation of attention is broadly ahead of smooth pursuit.
AB  - When moving through our environment, it is vital to preferentially process
      positions on our future path in order to react quickly to critical situations.
      During smooth pursuit, attention may be directed ahead with either a focused
      locus or a broad bias. We examined the 2D spatial extent of attention during a
      smooth pursuit task using both saccade (SRT) and manual (MRT) reaction times as
      measures of attentional allocation. Targets were flashed at various locations
      around current eye position while subjects pursued a moving target. Subjects made
      a saccade or pressed a button as soon as they perceived the target. Both SRTs and
      MRTs were shortest to targets flashed ahead of compared to behind the direction
      of pursuit across half of the visual field ahead of pursuit direction.
      Furthermore, we found an increase specific to SRTs at small target eccentricities
      directly ahead of pursuit, which may be related to an additional saccade trigger
      strategy; small saccades take longer to execute if smooth pursuit brings the eyes
      close to the target. In summary, both SRTs and MRTs revealed that attention is by
      default broadly allocated in the visual hemi-field ahead of the line of sight
      during smooth pursuit eye movements. This attentional bias may serve a predictive
      purpose for facilitating the processing of upcoming events.

PMID- 21071575
TI  - Perceptual learning of oriented gratings as revealed by classification images.
AB  - Classification image analysis is a psychophysical technique in which noise
      components of stimuli are analyzed to produce an image that reveals critical
      features of a task. Here we use classification images to gain greater
      understanding of perceptual learning. To achieve reasonable classification images
      within a single session, we developed an efficient classification image procedure
      that employed designer noise and a low-dimensional stimulus space. Subjects were
      trained across ten sessions to detect the orientation of a grating masked in
      noise, with an eleventh, test, session conducted using a stimulus orthogonal to
      the trained stimulus. As with standard perceptual learning studies, subjects
      showed improvements in performance metrics of accuracy, threshold, and reaction
      times. The clarity of the classification images and their correlation to an ideal
      target also improved across training sessions in an orientation-specific manner.
      Furthermore, image-based analyses revealed aspects of performance that could not
      be observed with standard performance metrics. Subjects with threshold
      improvements learned to use pixels across a wider area of the image, and, apposed
      to subjects without threshold improvements, showed improvements in both the
      bright and dark parts of the image. We conclude that classification image
      analysis is an important complement to traditional metrics of perceptual
      learning.

PMID- 21071576
TI  - Surround suppression and facilitation in the fovea: very long-range spatial
      interactions in contrast perception.
AB  - Surround modulation of perceived contrast has been almost exclusively studied in
      short-range conditions, i.e., in situations where a tiny gap, at most, separates
      center from surround. Existing long-range studies suggest that suppression
      extends to 12-cycle distance, whereas facilitation of perceived contrast is
      suggested to arise from visual field regions enclosing the center. In V1 neurons,
      however, long-range surround modulation involves both suppression and
      facilitation. Thus, we investigated short- and long-range surround modulation by
      measuring the perceived contrast of a center in the presence of a surround either
      near (0.3 cycles, 0.1 degree) or far (19.8 cycles, 6.6 degrees) from the center.
      This study demonstrates that in addition to the well-known suppression, surround
      modulation involves remarkably long-range facilitation of perceived contrast. At
      low center contrasts, the long-range facilitation was stronger than the long
      range suppression, whereas at high center contrast we found mainly long-range
      suppression. Because the current models of perceived contrast could not account
      for our data, we considered our results in the context of models developed for
      surround modulation in V1 neurons. However, neither mechanistic nor
      phenomenological models proved satisfactory. Moreover, with the current
      knowledge, it seems that straightforward pooling of V1 neurons' responses cannot
      account for surround modulation of perceived contrast.

PMID- 21071578
TI  - A migration signature and plasma biomarker panel for pancreatic adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma is a disease of extremely poor prognosis for
      which there are no reliable markers of asymptomatic disease. To identify
      pancreatic cancer biomarkers, we focused on a genomic interval proximal to the
      most common fragile site in the human genome, chromosome 3p12, which undergoes
      smoking-related breakage, loss of heterozygosity, and homozygous deletion as an
      early event in many epithelial tumors, including pancreatic cancers. Using a
      functional genomic approach, we identified a seven-gene panel (TNC, TFPI, TGFBI,
      SEL-1L, L1CAM, WWTR1, and CDC42BPA) that was differentially expressed across
      three different expression platforms, including pancreatic tumor/normal samples.
      In addition, Ingenuity Pathways Analysis (IPA) and literature searches indicated
      that this seven-gene panel functions in one network associated with cellular
      movement/morphology/development, indicative of a "migration signature" of the 3p
      pathway. We tested whether two secreted proteins from this panel, tenascin C
      (TNC) and tissue factor pathway inhibitor (TFPI), could serve as plasma
      biomarkers. Plasma ELISA assays for TFPI/TNC resulted in a combined area under
      the curve (AUC) of 0.88 and, with addition of CA19-9, a combined AUC for the
      three-gene panel (TNC/TFPI/CA19-9), of 0.99 with 100% specificity at 90%
      sensitivity and 97.22% sensitivity at 90% specificity. Validation studies using
      TFPI only in a blinded sample set increased the performance of CA19-9 from an AUC
      of 0.84 to 0.94 with the two-gene panel. Results identify a novel 3p pathway
      associated migration signature and plasma biomarker panel that has utility for
      discrimination of pancreatic cancer from normal controls and promise for clinical
      application.

PMID- 21071579
TI  - MicroRNAs 221/222 and genistein-mediated regulation of ARHI tumor suppressor gene
      in prostate cancer.
AB  - ARHI is an imprinted tumor suppressor gene and is downregulated in various
      malignancies. However, ARHI expression, function, and mechanisms of action in
      prostate cancer have not been reported. Here, we report that ARHI mRNA and
      protein levels were downregulated in prostate cancer tissues compared with
      adjacent normal tissues. Overexpression of ARHI inhibited cell proliferation,
      colony formation, invasion, and induced apoptosis. Further studies on a new
      mechanism of ARHI downregulation showed a significant inverse relationship
      between ARHI and miR-221 and 222, which were upregulated in prostate cancer cell
      lines. Transfection of miR-221 and 222 inhibitors into PC-3 cells caused a
      significant induction of ARHI expression. A direct interaction of miR-221 or 222
      with a target site on the 3'UTR of ARHI was confirmed by a dual luciferase pMIR
      REPORT assay. Finally, we also found that genistein upregulates ARHI by
      downregulating miR-221 and 222 in PC-3 cells. In conclusion, ARHI is a tumor
      suppressor gene downregulated in prostate cancer, and overexpression of ARHI can
      inhibit cell proliferation, colony formation, and invasion. This study
      demonstrates for the first time that prostate cancer cells have decreased level
      of ARHI which could be caused by direct targeting of 3'UTR of ARHI by miR221/222.
      Genistein, a potential nontoxic chemopreventive agent, restores expression of
      ARHI and may be an important dietary therapeutic agent for treating prostate
      cancer.

PMID- 21071580
TI  - Acyclic retinoid inhibits diethylnitrosamine-induced liver tumorigenesis in obese
      and diabetic C57BLKS/J- +(db)/+Lepr(db) mice.
AB  - Obesity and the related metabolic abnormalities are associated with increased
      risk of hepatocellular carcinoma (HCC). Malfunctioning of retinoid X receptor
      (RXR) alpha due to phosphorylation by Ras/MAPK also plays a critical role in
      liver carcinogenesis. In the present study, we examined the effects of acyclic
      retinoid (ACR), which targets RXRalpha, on the development of diethylnitrosamine
      (DEN)-induced liver tumorigenesis in C57BLKS/J- +Lepr(db)/+Lepr(db) (db/db) obese
      mice. Male db/db mice were given tap water containing 40 ppm DEN for 2 weeks,
      after which they were fed a diet containing 0.03% or 0.06% of ACR throughout the
      experiment. In mice treated with either dose of ACR for 34 weeks, the development
      of liver cell adenomas was significantly inhibited as compared with basal diet
      fed mice. ACR markedly inhibited the activation of Ras and phosphorylation of the
      ERK (extracellular signal-regulated kinase) and RXRalpha proteins in the livers
      of experimental mice. It also increased the expression of RAR beta and p21(CIP1)
      mRNA while decreasing the expression of cyclin D1, c-Fos, and c-Jun mRNA in the
      liver, thereby restoring RXRalpha function. Administration of ACR improved liver
      steatosis and activated the AMPK protein. The serum levels of insulin decreased
      by ACR treatment, whereas the quantitative insulin sensitivity check index
      (QUICKI) values increased, indicating improved insulin sensitivity. The serum
      levels of TNF-alpha and the expression levels of TNF- alpha, IL-6, and IL-1 beta
      mRNA in the livers of DEN-treated db/db mice were decreased by ACR treatment,
      suggesting attenuation of the chronic inflammation induced by excessive fatty
      deposits. ACR may be, therefore, useful in the chemoprevention of obesity-related
      HCC.

PMID- 21071581
TI  - The provision of a percutaneously placed enteral tube feeding service.
AB  - There is overwhelming evidence that the maintenance of enteral feeding is
      beneficial in patients in whom oral access has been diminished or lost. Short
      term enteral access is usually achieved via naso-enteral tube placement. For
      longer term tube feeding there are recognised advantages for enteral feeding
      tubes placed percutaneously. The provision of a percutaneous enteral tube feeding
      service should be within the remit of the hospital nutrition support team (NST).
      This designated team should provide a framework for patient selection, pre
      assessment and post-procedural care. Close working relations with community-based
      services should be established. An accredited therapeutic endoscopist should be a
      member of the NST and direct the technical aspects of the service. Every
      endoscopy unit in an acute hospital setting should provide a basic percutaneous
      endoscopic gastrostomy (PEG) service. This should include provision for fitting a
      PEG jejunal extension (PEGJ) if required. Specialist units should be identified
      where a more comprehensive service is provided, including direct jejunal
      placement (DPEJ), as well as radiological and laparoscopically placed tubes. Good
      understanding of the indications for percutaneous enteral tube feeding will
      prevent inappropriate procedures and ensure that the correct feeding route is
      selected at the appropriate time. Each unit should adopt and become familiar with
      a limited range of PEG tube equipment. Careful adherence to the important
      technical details of tube insertion will reduce peri-procedural complications.
      Post-procedural complications remain relatively common, however, and an awareness
      of the correct approach to managing them is essential for all clinicians involved
      in providing a percutaneous enteral tube feeding service. Finally, ethical
      considerations should always be taken into account when considering long-term
      enteral feeding, especially for patients with a poor quality of life.

PMID- 21071582
TI  - A case of bleeding oesophageal varices.

PMID- 21071583
TI  - The brain to gut pathway: a possible route of prion transmission.
AB  - OBJECTIVE: The intestine is recognised to play a key role in the transmission of
      prion diseases. These diseases are associated with pathological isoforms
      (PrP(Sc)) of the normal cellular prion protein (PrP(C)) and can be transmitted
      between individuals or arise spontaneously. The brain, as the primary site of
      prion replication, could provide infectious prions to peripheral tissues. Here,
      we examine whether the brain is a source of intestinal prion accumulation.
      METHODS: Following intracerebral inoculation with human origin prions the ileums
      of BalbC mice with clinical prion disease were assessed by Western immunoblot and
      immunohistochemical analysis for the presence of PrP(Sc) and the survival of
      enteric glial cells (EGCs) and specific neuronal subpopulations in the myenteric
      and submucosal plexus. RESULTS: PrP(Sc) was detected in the ileum of 13/13 mice
      following intracerebral inoculation with prions and 0/4 saline-inoculated mice.
      PrP(Sc) was localised at detectable levels in the Peyer's patches of infected
      mice. Investigation of neuronal subpopulations revealed a significant decrease in
      neurofilament reactive neurons (11+/-8%, p<0.05, n=5) compared with saline
      inoculated mice (23+/-5%, n=3). Neuronal nitric oxide synthase (nNOS) and
      tyrosine hydroxylase reactive neurons were decreased in some (2 of 4 and 1 of 3,
      respectively) but not all prion-infected mice, whereas calretinin and vasoactive
      intestinal peptide reactive neurons were unaffected. EGCs were highly distorted
      in circumscribed ganglia of the myenteric plexus. In areas of glial derangement,
      the neurons showed undefined outlines and faint cytoplasmic immunoreactivity for
      the pan-neuronal marker Hu and loss of nNOS reactivity. CONCLUSIONS: The present
      work shows that PrP(Sc) can be transmitted from the brain to the intestine. This
      causes pathological changes in enteric glia and neurons. We conclude that PrP(Sc)
      of brain origin finds a substrate in the naturally occurring PrP(C) of EGCs and
      neurons. This results in a reservoir of PrP(Sc) in the intestine, which may
      represent a source of prion disease transmission through surgical procedures and
      environmental contamination.

PMID- 21071584
TI  - E-health empowers patients with ulcerative colitis: a randomised controlled trial
      of the web-guided 'Constant-care' approach.
AB  - BACKGROUND: The natural history of ulcerative colitis requires continuous
      monitoring of medical treatment via frequent outpatient visits. The European
      health authorities' focus on e-health is increasing. Lack of easy access to
      inflammatory bowel disease (IBD) clinics, patients' education and understanding
      of the importance of early treatment at relapse is leading to poor compliance. To
      overcome these limitations a randomised control trial 'Constant-care' was
      undertaken in Denmark and Ireland. METHODS: 333 patients with mild/moderate
      ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either
      a web-group receiving disease specific education and self-treatment via
      http://www.constant-care.dk or a control group continuing the usual care for 12
      months. A historical control group was included to test the comparability with
      the control group. We investigated: feasibility of the approach, its influence on
      patients' compliance, knowledge, quality of life (QoL), disease outcomes, safety
      and health care costs. RESULTS: 88% of the web patients preferred using the new
      approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark
      and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and
      QoL were significantly improved in web patients. Median relapse duration was 18
      days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the
      control group. The number of acute and routine visits to the outpatient clinic
      was lower in the web than in the control group, resulting in a saving of 189
      euro/patient/year. No difference in the relapse frequency, hospitalisation,
      surgery or adverse events was observed. The historical control group was
      comparable with the control group. CONCLUSION: The new web-guided approach on
      http://www.constant-care.dk is feasible, safe and cost effective. It empowers
      patients with ulcerative colitis without increasing their morbidity and
      depression. It has yet to be shown whether this strategy can change the natural
      disease course of ulcerative colitis in the long term.

PMID- 21071585
TI  - Running with regulation.

PMID- 21071586
TI  - In vivo estimation of the contribution of elastin and collagen to the mechanical
      properties in the human abdominal aorta: effect of age and sex.
AB  - The mechanical properties of the aorta affect cardiac function and are related to
      cardiovascular morbidity/mortality. This study was designed to evaluate the
      isotropic (mainly elastin, elastin(iso)) and anisotropic (mainly collagen,
      collagen(ani)) material parameters within the human aorta in vivo. Thirty healthy
      men and women in three different age categories (23-30, 41-54, and 67-72 yr) were
      included. A novel mechanical model was used to identify the mechanical properties
      and the strain field with aid of simultaneously recorded pressure and radius in
      the abdominal aorta. The magnitudes of the material parameters relating to both
      the stiffness of elastin(iso) and collagen(ani) were in agreement with earlier in
      vitro studies. The load-bearing fraction attributed to collagen(ani) oscillated
      from 10 to 30% between diastolic and systolic pressures during the cardiac cycle.
      With age, stiffness of elastin(iso) increased in men, despite the decrease in
      elastin content that has been found due to elastolysis. Furthermore, an increase
      in stiffness of collagen(ani) at high physiological pressure was found. This
      might be due to increased glycation, as well as changed isoforms of collagen in
      the aortic wall with age. A marked sex difference was observed, with a much less
      age-related effect, both on elastin(iso) and collagen(ani) stiffness in women.
      Possible factors of importance could be the effect of sex hormones, as well as
      differing collagen isoforms, between the sexes.

PMID- 21071587
TI  - Cerebral vasoreactivity during hypercapnia is reset by augmented sympathetic
      influence.
AB  - Sympathetic nerve activity influences cerebral blood flow, but it is unknown
      whether augmented sympathetic nerve activity resets cerebral vasoreactivity to
      hypercapnia. This study tested the hypothesis that cerebral vasodilation during
      hypercapnia is restrained by lower-body negative pressure (LBNP)-stimulated
      sympathoexcitation. Cerebral hemodynamic responses were assessed in nine healthy
      volunteers [age 25 yr (SD 3)] during rebreathing-induced increases in partial
      pressure of end-tidal CO(2) (Pet(CO(2))) at rest and during LBNP. Cerebral
      hemodynamic responses were determined by changes in flow velocity of middle
      cerebral artery (MCAV) using transcranial Doppler sonography and in regional
      cerebral tissue oxygenation (ScO(2)) using near-infrared spectroscopy. Pet(CO(2))
      values during rebreathing were similarly increased from 41.9 to 56.5 mmHg at rest
      and from 40.7 to 56.0 mmHg during LBNP of -15 Torr. However, the rates of
      increases in MCAV and in ScO(2) per unit increase in Pet(CO(2)) (i.e., the slopes
      of MCAV/Pet(CO(2)) and ScO(2)/Pet(CO(2))) were significantly (P <=0.05) decreased
      from 2.62 +/- 0.16 cm.s(-1).mmHg(-1) and 0.89 +/- 0.10%/mmHg at rest to 1.68 +/-
      0.18 cm.s(-1).mmHg(-1) and 0.63 +/- 0.07%/mmHg during LBNP. In conclusion, the
      sensitivity of cerebral vasoreactivity to hypercapnia, in terms of the rate of
      increases in MCAV and in ScO(2), is diminished by LBNP-stimulated
      sympathoexcitation.

PMID- 21071588
TI  - Dietary nitrate supplementation reduces the O2 cost of walking and running: a
      placebo-controlled study.
AB  - Dietary supplementation with beetroot juice (BR) has been shown to reduce resting
      blood pressure and the O(2) cost of submaximal exercise and to increase tolerance
      to high-intensity cycling. We tested the hypothesis that the physiological
      effects of BR were consequent to its high NO(3)(-) content per se, and not the
      presence of other potentially bioactive compounds. We investigated changes in
      blood pressure, mitochondrial oxidative capacity (Q(max)), and physiological
      responses to walking and moderate- and severe-intensity running following dietary
      supplementation with BR and NO(3)(-)-depleted BR [placebo (PL)]. After control
      (nonsupplemented) tests, nine healthy, physically active male subjects were
      assigned in a randomized, double-blind, crossover design to receive BR (0.5
      l/day, containing ~6.2 mmol of NO(3)(-)) and PL (0.5 l/day, containing ~0.003
      mmol of NO(3)(-)) for 6 days. Subjects completed treadmill exercise tests on days
      4 and 5 and knee-extension exercise tests for estimation of Q(max) (using (31)P
      magnetic resonance spectroscopy) on day 6 of the supplementation periods.
      Relative to PL, BR elevated plasma NO(2)(-) concentration (183 +/- 119 vs. 373 +/
      211 nM, P < 0.05) and reduced systolic blood pressure (129 +/- 9 vs. 124 +/- 10
      mmHg, P < 0.01). Q(max) was not different between PL and BR (0.93 +/- 0.05 and
      1.05 +/- 0.22 mM/s, respectively). The O(2) cost of walking (0.87 +/- 0.12 and
      0.70 +/- 0.10 l/min in PL and BR, respectively, P < 0.01), moderate-intensity
      running (2.26 +/- 0.27 and 2.10 +/- 0.28 l/min in PL and BR, respectively, P <
      0.01), and severe-intensity running (end-exercise O(2) uptake = 3.77 +/- 0.57 and
      3.50 +/- 0.62 l/min in PL and BL, respectively, P < 0.01) was reduced by BR, and
      time to exhaustion during severe-intensity running was increased by 15% (7.6 +/-
      1.5 and 8.7 +/- 1.8 min in PL and BR, respectively, P < 0.01). In contrast,
      relative to control, PL supplementation did not alter plasma NO(2)(-)
      concentration, blood pressure, or the physiological responses to exercise. These
      results indicate that the positive effects of 6 days of BR supplementation on the
      physiological responses to exercise can be ascribed to the high NO(3)(-) content
      per se.

PMID- 21071589
TI  - Evidence for minimal oxygen heterogeneity in the healthy human pulmonary acinus.
AB  - It has been suggested that the human pulmonary acinus operates at submaximal
      efficiency at rest due to substantial spatial heterogeneity in the oxygen partial
      pressure (Po(2)) in alveolar air within the acinus. Indirect measurements of
      alveolar air Po(2) could theoretically mask significant heterogeneity if intra
      acinar perfusion is well matched to Po(2). To investigate the extent of intra
      acinar heterogeneity, we developed a computational model with anatomically based
      structure and biophysically based equations for gas exchange. This model yields a
      quantitative prediction of the intra-acinar O(2) distribution that cannot be
      measured directly. Temporal and spatial variations in Po(2) in the intra-acinar
      air and blood are predicted with the model. The model, representative of a single
      average acinus, has an asymmetric multibranching respiratory airways geometry
      coupled to a symmetric branching conducting airways geometry. Advective and
      diffusive O(2) transport through the airways and gas exchange into the capillary
      blood are incorporated. The gas exchange component of the model includes
      diffusion across the alveolar air-blood membrane and O(2)-hemoglobin binding.
      Contrary to previous modeling studies, simulations show that the acinus functions
      extremely effectively at rest, with only a small degree of intra-acinar Po(2)
      heterogeneity. All regions of the model acinus, including the peripheral
      generations, maintain a Po(2) >100 mmHg. Heterogeneity increases slightly when
      the acinus is stressed by exercise. However, even during exercise the acinus
      retains a reasonably homogeneous gas phase.

PMID- 21071590
TI  - Male human motor cortex stimulus-response characteristics are not altered by
      aging.
AB  - Evidence suggests that there are aging-related changes in corticospinal stimulus
      response curve characteristics in later life. However, there is also limited
      evidence that these changes may only be evident in postmenopausal women and not
      in men. This study compared corticospinal stimulus-response curves from a group
      of young men [19.8 +/- 1.6 yr (range 17-23 yr)] and a group of old men [n = 18,
      aged 64.1 +/- 5.0 yr (range 55-73 yr)]. Transcranial magnetic stimulation (TMS)
      over the contralateral motor cortex was used to evoke motor potentials at a range
      of stimulus intensities in the first dorsal interosseous muscle of each hand
      separately. There was no effect of age group or hemisphere (i.e., left vs. right
      motor cortex) on motor evoked potential (MEP) amplitude or any other stimulus
      response characteristic. MEP variability was strongly modulated by resting motor
      threshold but not by age. M-wave (but not F-wave) amplitude was reduced in old
      men, but expressing MEP amplitude as a ratio of M-wave amplitude did not reveal
      any age-related differences in cortically evoked stimulus-response
      characteristics. We conclude that male corticospinal stimulus-response
      characteristics are not altered by advancing age and that previously reported age
      related changes in motor cortical excitability assessed with TMS are likely due
      to changes inherent in the female participants only. Future studies are warranted
      to fully elucidate the relationship between, and functional significance of,
      changes in circulating neuroactive sex hormones and motor function in later life.

PMID- 21071591
TI  - Cerebral vascular adaptation to pregnancy and its role in the neurological
      complications of eclampsia.
AB  - The cerebral circulation has a central role in mediating the neurological
      complications of eclampsia, yet our understanding of how pregnancy and
      preeclampsia affect this circulation is severely limited. Here, we show that
      pregnancy causes outward remodeling of penetrating arterioles and increased
      capillary density in the brain due to activation of peroxisome proliferator
      activated receptor-gamma (PPARgamma), a transcription factor involved in
      cerebrovascular remodeling and highly activated in pregnancy. Pregnancy-induced
      PPARgamma activation also significantly affected cerebral hemodynamics,
      decreasing vascular resistance and increasing cerebral blood flow by ~40% in
      response to acute hypertension that caused breakthrough of autoregulation. These
      structural and hemodynamic changes in the brain during pregnancy were associated
      with substantially increased blood-brain barrier permeability, an effect that
      could promote passage of damaging proteins into the brain and cause the
      neurological complications of eclampsia, including seizure.

PMID- 21071592
TI  - Intragastric administration of capsiate, a transient receptor potential channel
      agonist, triggers thermogenic sympathetic responses.
AB  - The sympathetic thermoregulatory system controls the magnitude of adaptive
      thermogenesis in correspondence with the environmental temperature or the state
      of energy intake and plays a key role in determining the resultant energy
      storage. However, the nature of the trigger initiating this reflex arc remains to
      be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we
      examined the involvement of specific activation of transient receptor potential
      (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic
      system by measuring the efferent activity of the postganglionic sympathetic nerve
      innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric
      administration of capsiate resulted in a time- and dose-dependent increase in
      integrated BAT sympathetic nerve activity (SNA) over 180 min, which was
      characterized by an emergence of sporadic high-activity phases composed of low
      frequency bursts. This increase in BAT SNA was abolished by blockade of TRP
      channels as well as of sympathetic ganglionic transmission and was inhibited by
      ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited
      to BAT and did not occur in the heart or pancreas. These results point to a
      neural pathway enabling the selective activation of the central network
      regulating the BAT SNA in response to a specific stimulation of gastrointestinal
      TRP channels and offer important implications for understanding the dietary
      dependent regulation of energy metabolism and control of obesity.

PMID- 21071593
TI  - Ethyl gallate, a scavenger of hydrogen peroxide that inhibits lysozyme-induced
      hydrogen peroxide signaling in vitro, reverses hypotension in canine septic
      shock.
AB  - Although hydrogen peroxide (H2O2) is a well-described reactive oxygen species
      that is known for its cytotoxic effects and associated tissue injury, H2O2 has
      recently been established as an important signaling molecule. We previously
      demonstrated that lysozyme (Lzm-S), a mediator of sepsis that is released from
      leukocytes, could produce vasodilation in a phenylephrine-constricted carotid
      artery preparation by H2O2 signaling. We found that Lzm-S could intrinsically
      generate H2O2 and that this generation activated H2O2-dependent pathways. In the
      present study, we used this carotid artery preparation as a bioassay to define
      those antioxidants that could inhibit Lzm-S's vasodilatory effect. We then
      determined whether this antioxidant could reverse the hypotension that developed
      in an Escherichia coli bacteremic model. Of the many antioxidants tested, we
      found that ethyl gallate (EG), a nonflavonoid phenolic compound, was favorable in
      inhibiting Lzm-S-induced vasodilation. In our E. coli model, we found that EG
      reversed the hypotension that developed in this model and attenuated end-organ
      dysfunction. By fluorometric H2O2 assay and electrochemical probe techniques, we
      showed that EG could scavenge H2O2 and that it could reduce H2O2 production in
      model systems. These results show that EG, an antioxidant that was found to
      scavenge H2O2 in vitro, was able to attenuate cardiovascular dysfunction in a
      canine in vivo preparation. Antioxidants such as EG may be useful in the
      treatment of hemodynamic deterioration in septic shock.

PMID- 21071594
TI  - Double-stranded RNA-dependent protein kinase activation modulates endotoxin
      induced diaphragm weakness.
AB  - Diaphragm caspase-8 activation plays a key role in modulating sepsis-induced
      respiratory muscle dysfunction. It is also known that double-stranded RNA
      dependent protein kinase (PKR) is a regulator of caspase-8 activation in neural
      tissue. We tested the hypothesis that the PKR pathway modulates sepsis-induced
      diaphragmatic caspase-8 activation. We first evaluated the time course of
      diaphragm PKR activation following endotoxin administration in mice. We then
      determined whether administration of a PKR inhibitor (2-aminopurine) prevents
      endotoxin-induced diaphragm caspase-8 activation and contractile dysfunction in
      mice. Finally, we investigated if inhibition of PKR (using either 2-aminopurine
      or transfection with dominant-negative PKR) blocks caspase-8 activation in
      cytokine treated C2C12 cells. Endotoxin markedly activated diaphragm PKR (with
      increases in both active phospho-PKR protein levels, P < 0.03, and directly
      measured PKR activity, P < 0.01) and increased active caspase-8 levels (P <
      0.01). Inhibition of PKR with 2-aminopurine prevented endotoxin-induced diaphragm
      caspase-8 activation (P < 0.01) and diaphragm weakness (P < 0.001). Inhibition of
      PKR with either 2-aminopurine or transfection with dominant-negative PKR blocked
      caspase-8 activation in isolated cytokine-treated C2C12 cells. These data
      implicate PKR activation as a major factor mediating cytokine-induced skeletal
      muscle caspase-8 activation and weakness.

PMID- 21071595
TI  - Julius H. Comroe, Jr., distinguished lecture: central chemoreception: then ...
      and now.
AB  - The 2010 Julius H. Comroe, Jr., Lecture of the American Physiological Society
      focuses on evolving ideas in chemoreception for CO2/pH in terms of what is
      "sensed," where it is sensed, and how the sensed information is used
      physiologically. Chemoreception is viewed as involving neurons (and glia) at many
      sites within the hindbrain, including, but not limited to, the retrotrapezoid
      nucleus, the medullary raphe, the locus ceruleus, the nucleus tractus solitarius,
      the lateral hypothalamus (orexin neurons), and the caudal ventrolateral medulla.
      Central chemoreception also has an important nonadditive interaction with
      afferent information arising at the carotid body. While ventilation has been
      viewed as the primary output variable, it appears that airway resistance,
      arousal, and blood pressure can also be significantly affected. Emphasis is
      placed on the importance of data derived from studies performed in the absence of
      anesthesia.

PMID- 21071596
TI  - Bronchodilation response to deep inspirations in asthma is dependent on airway
      distensibility and air trapping.
AB  - In healthy individuals, deep inspirations (DIs) have a potent bronchodilatory
      ability against methacholine (MCh)-induced bronchoconstriction. This is variably
      attenuated in asthma. We hypothesized that inability to bronchodilate with DIs is
      related to reduced airway distensibility. We examined the relationship between DI
      induced bronchodilation and airway distensibility in 15 asthmatic individuals
      with a wide range of baseline lung function [forced expired volume in 1 s
      (FEV(1)) = 60-99% predicted]. After abstaining from DIs for 20 min, subjects
      received a single-dose MCh challenge and then asked to perform DIs. The
      effectiveness of DIs was assessed by the ability of the subjects to improve
      FEV(1). The same subjects were studied by two sets of high-resolution CT scans,
      one at functional residual capacity (FRC) and one at total lung capacity (TLC).
      In each subject, the areas of 21-41 airways (0.8-6.8 mm diameter at FRC) were
      matched and measured, and airway distensibility (increase in airway diameter from
      FRC to TLC) was calculated. The bronchodilatory ability of DIs was significantly
      lower in individuals with FEV(1) <75% predicted than in those with FEV(1) >=75%
      predicted (15 +/- 11% vs. 46 +/- 9%, P = 0.04) and strongly correlated with
      airway distensibility (r = 0.57, P = 0.03), but also with residual volume
      (RV)/TLC (r = -0.63, P = 0.01). In multiple regression, only RV/TLC was a
      significant determinant of DI-induced bronchodilation. These relationships were
      lost when the airways were examined after maximal bronchodilation with albuterol.
      Our data indicate that the loss of the bronchodilatory effect of DI in asthma is
      related to the ability to distend the airways with lung inflation, which is, in
      turn, related to the extent of air trapping and airway smooth muscle tone. These
      relationships only exist in the presence of airway tone, indicating that
      structural changes in the conducting airways visualized by high-resolution CT do
      not play a pivotal role.

PMID- 21071597
TI  - Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase
      independent activation of mTORC1.
AB  - For over 10 years, we have known that the activation of the mammalian target of
      rapamycin complex 1 (mTORC1) has correlated with the increase in skeletal muscle
      size and strength that occurs following resistance exercise. Initial cell culture
      and rodent models of muscle growth demonstrated that the activation of mTORC1 is
      common to hypertrophy induced by growth factors and increased loading. The
      further observation that high loads increased the local production of growth
      factors led to the paradigm that resistance exercise stimulates the autocrine
      production of factors that act on membrane receptors to activate mTORC1, and this
      results in skeletal muscle hypertrophy. Over the last few years, there has been a
      paradigm shift. From both human and rodent studies, it has become clear that the
      phenotypic and molecular responses to resistance exercise occur in a growth
      factor-independent manner. Although the mechanism of load-induced mTORC1
      activation remains to be determined, it is clear that it does not require
      classical growth factor signaling.

PMID- 21071599
TI  - Increasing photosynthetic carbon assimilation in C3 plants to improve crop yield:
      current and future strategies.

PMID- 21071598
TI  - Alstrom Syndrome protein ALMS1 localizes to basal bodies of cochlear hair cells
      and regulates cilium-dependent planar cell polarity.
AB  - Alstrom Syndrome is a life-threatening disease characterized primarily by
      numerous metabolic abnormalities, retinal degeneration, cardiomyopathy, kidney
      and liver disease, and sensorineural hearing loss. The cellular localization of
      the affected protein, ALMS1, has suggested roles in ciliary function and/or
      ciliogenesis. We have investigated the role of ALMS1 in the cochlea and the
      pathogenesis of hearing loss in Alstrom Syndrome. In neonatal rat organ of Corti,
      ALMS1 was localized to the basal bodies of hair cells and supporting cells. ALMS1
      was also evident at the basal bodies of differentiating fibrocytes and marginal
      cells in the lateral wall. Centriolar ALMS1 expression was retained into
      maturity. In Alms1-disrupted mice, which recapitulate the neurosensory deficits
      of human Alstrom Syndrome, cochleae displayed several cyto-architectural defects
      including abnormalities in the shape and orientation of hair cell stereociliary
      bundles. Developing hair cells were ciliated, suggesting that ciliogenesis was
      largely normal. In adult mice, in addition to bundle abnormalities, there was an
      accelerated loss of outer hair cells and the progressive appearance of large
      lesions in stria vascularis. Although the mice progressively lost distortion
      product otoacoustic emissions, suggesting defects in outer hair cell
      amplification, their endocochlear potentials were normal, indicating the strial
      atrophy did not affect its function. These results identify previously
      unrecognized cochlear histopathologies associated with this ciliopathy that (i)
      implicate ALMS1 in planar cell polarity signaling and (ii) suggest that the loss
      of outer hair cells causes the majority of the hearing loss in Alstrom Syndrome.

PMID- 21071602
TI  - Feasibility of including cellular telephone numbers in random digit dialing for
      epidemiologic case-control studies.
AB  - The usefulness of landline random digit dialing (RDD) in epidemiologic studies is
      threatened by the rapid increase in households with only cellular telephone
      service. This study assessed the feasibility of including cellular telephone
      numbers in RDD and differences between young adults with landline telephones and
      those with only cellular telephones. Between 2008 and 2009, a total of 9,023
      cellular telephone numbers were called and 43.8% were successfully screened; 248
      men and 249 women who resided in 3 Washington State counties, were 20-44 years of
      age, and used only cellular telephones were interviewed. They were compared with
      332 men and 526 women with landline telephones interviewed as controls for 2 case
      control studies conducted in parallel with cellular telephone interviewing.
      Cellular-only users were more likely to be college educated and less likely to
      have fathered/birthed a child than were their landline counterparts. Male
      cellular-only users were less likely to be obese and more likely to exercise, to
      be Hispanic, and to have lower incomes, while female cellular-only users were
      more likely to be single than landline respondents. Including cellular telephone
      numbers in RDD is feasible and should be incorporated into epidemiologic studies
      that rely on this method to ascertain subjects, although low screening rates
      could hamper the representativeness of such a sample.

PMID- 21071601
TI  - Two host cytoplasmic effectors are required for pathogenesis of Phytophthora
      sojae by suppression of host defenses.
AB  - Phytophthora sojae encodes hundreds of putative host cytoplasmic effectors with
      conserved FLAK motifs following signal peptides, termed crinkling- and necrosis
      inducing proteins (CRN) or Crinkler. Their functions and mechanisms in
      pathogenesis are mostly unknown. Here, we identify a group of five P. sojae
      specific CRN-like genes with high levels of sequence similarity, of which three
      are putative pseudogenes. Functional analysis shows that the two functional genes
      encode proteins with predicted nuclear localization signals that induce
      contrasting responses when expressed in Nicotiana benthamiana and soybean
      (Glycine max). PsCRN63 induces cell death, while PsCRN115 suppresses cell death
      elicited by the P. sojae necrosis-inducing protein (PsojNIP) or PsCRN63.
      Expression of CRN fragments with deleted signal peptides and FLAK motifs
      demonstrates that the carboxyl-terminal portions of PsCRN63 or PsCRN115 are
      sufficient for their activities. However, the predicted nuclear localization
      signal is required for PsCRN63 to induce cell death but not for PsCRN115 to
      suppress cell death. Furthermore, silencing of the PsCRN63 and PsCRN115 genes in
      P. sojae stable transformants leads to a reduction of virulence on soybean.
      Intriguingly, the silenced transformants lose the ability to suppress host cell
      death and callose deposition on inoculated plants. These results suggest a role
      for CRN effectors in the suppression of host defense responses.

PMID- 21071600
TI  - Manipulating broad-spectrum disease resistance by suppressing pathogen-induced
      auxin accumulation in rice.
AB  - Breeding crops with the quality of broad-spectrum disease resistance using
      genetic resources is one of the principal goals of crop improvement. However, the
      molecular mechanism of broad-spectrum resistance remains largely unknown. Here,
      we show that GH3-2, encoding an indole-3-acetic acid (IAA)-amido synthetase,
      mediates a broad-spectrum resistance to bacterial Xanthomonas oryzae pv oryzae
      and Xanthomonas oryzae pv oryzicola and fungal Magnaporthe grisea in rice (Oryza
      sativa). IAA, the major form of auxin in rice, results in rice more vulnerable to
      the invasion of different types of pathogens, which is at least partly due to IAA
      induced loosening of the cell wall, the natural protective barrier of plant cells
      to invaders. X. oryzae pv oryzae, X. oryzae pv oryzicola, and M. grisea secrete
      IAA, which, in turn, may induce rice to synthesize its own IAA at the infection
      site. IAA induces the production of expansins, the cell wall-loosening proteins,
      and makes rice vulnerable to pathogens. GH3-2 is likely contributing to a minor
      quantitative trait locus for broad-spectrum resistance. Activation of GH3-2
      inactivates IAA by catalyzing the formation of an IAA-amino acid conjugate, which
      results in the suppression of expansin genes. Thus, GH3-2 mediates basal
      resistance by suppressing pathogen-induced IAA accumulation. It is expected that,
      regulated by a pathogen-induced strong promoter, GH3-2 alone may be used for
      breeding rice with a broad-spectrum disease resistance.

PMID- 21071603
TI  - Application of the time-series approach to assess the temporal trend of racial
      disparity in chlamydia prevalence in the US National Job Training Program.
AB  - The authors applied a time-series approach to assess the temporal trend of racial
      disparity in chlamydia prevalence between young, socioeconomically disadvantaged
      blacks and whites entering the US National Job Training Program. Racial disparity
      was defined as the arithmetic difference between age group-, specimen type-, and
      region of residence-standardized chlamydia prevalences in blacks and whites. A
      regression with autoregressive moving average errors model was employed to adjust
      for serial correlation. Data from 46,849 women (2006-2008) and 136,892 men (2004
      2008) were analyzed. Racial disparity significantly decreased among women (by an
      average of 0.122% per 2-month interval; P < 0.05) but not among men (-0.010%, P =
      0.57). Chlamydia prevalence significantly declined for black women (-0.139% per 2
      month interval; P = 0.004), black men (-0.045%, P < 0.001), and white men (
      0.035%, P = 0.002) but not for white women (-0.028%, P = 0.413). Despite the
      decreases among black women and black men, the black-white disparities remained
      high for both sexes; in 2008, the racial disparity was 8.1% (95% confidence
      interval: 6.8, 9.3) for women and 9.0% (95% confidence interval: 8.4, 9.6) for
      men. These findings suggest that current chlamydia control efforts may be
      reaching young black men and women but need to be scaled up or modified to
      address the excess risk among blacks.

PMID- 21071604
TI  - The factor XII -4C>T variant and risk of common thrombotic disorders: A HuGE
      review and meta-analysis of evidence from observational studies.
AB  - Coagulation factor XII is involved in thrombus formation and therefore may play a
      role in the etiology of thrombotic disorders. A common variant in the factor XII
      (F12) gene (-4C>T, rs1801020) results in decreased plasma levels of this
      coagulation factor. The existence of associations between low factor XII levels
      or F12 variants and thrombotic outcomes has been debated for more than a decade.
      The authors conducted a review and meta-analysis to evaluate the evidence for an
      association between F12 -4C>T and 2 common thrombotic outcomes: venous
      thromboembolism and myocardial infarction, which are hypothesized to share some
      etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through
      July 2009 to identify relevant epidemiologic studies, and data were summarized
      using random-effects meta-analysis. Sixteen candidate gene studies (4,386 cases,
      40,089 controls) were analyzed. None of the investigated contrasts reached
      statistical significance at P < 0.05, apart from a very weak association with
      myocardial infarction for the TT + CT versus CC contrast (odds ratio = 1.13, 95%
      confidence interval: 1.00, 1.27). Overall, based on the synthesis of
      observational studies, the evidence for an association between F12 -4C>T and
      venous thromboembolism and myocardial infarction is weak.

PMID- 21071605
TI  - Job strain and the risk of depression: is reporting biased?
AB  - It is unknown whether the relation between job strain and depression reflects
      causal characteristics of the working environment or reporting bias. The authors
      investigated reporting bias by analyzing individual versus work-unit measures of
      job strain and the risk of depressive symptoms (n = 287) and a diagnosis of
      depression (n = 97) among 4,291 employees within 378 work units in Aarhus,
      Denmark, 2007. All participants reported psychological demands and decision
      latitude, and the authors estimated mean values for each work unit. The odds
      ratios predicting depressive symptoms or a diagnosis of depression for the
      highest versus the lowest levels of individual, self-reported high psychological
      demands and low decision latitude were significantly increased above 2.5. When
      participants were classified by the work-unit mean levels, these associations
      were substantially smaller. For depressive symptoms, the odds ratios were 1.49
      (95% confidence interval (CI): 0.88, 2.53) and 1.08 (95% CI: 0.84, 1.39),
      respectively, for psychological demands and decision latitude. For a diagnosis of
      depression, the odds ratios were 1.33 (95% CI: 0.57, 3.09) and 1.02 (95% CI:
      0.68, 1.56), respectively, for psychological demands and decision latitude. These
      findings indicate that reporting bias inflates associations between job strain
      and the occurrence of depression, if studies rely on individual self-reports.

PMID- 21071606
TI  - Improving flow and spillage characteristics of range hoods by using an inclined
      air-curtain technique.
AB  - The current study developed a new type of range hood, which was termed an
      'inclined air-curtain range hood', in order to improve the flow and performance
      of the conventionally used wall-mounted range hood. The flow characteristics and
      oil mist spillages of air-curtain and conventional range hoods under the
      influences of both a mannequin presence and a simulated walk-by motion were
      experimentally examined. The study examined flow patterns by using a laser-light
      sheet-assisted smoke-flow visualization technique and diagnosed spillages by
      using the tracer gas concentration test method. A mannequin presented in front of
      the conventional hood induced turbulent dispersion of oil mists toward the chest
      and nose of the mannequin owing to the complex interaction among the suction,
      wake, and wall effect, while the inclined air-curtain hood presented excellent
      hood performance by isolating the oil mists from the mannequin with an air
      curtain and therefore could reduce spillages out into the atmosphere and the
      mannequin's breathing zone. Both flow visualization and the tracer gas test
      indicated that the air-curtain hood had excellent 'robustness' over the
      conventional hood in resisting the influence of walk-by motion. The air-curtain
      technique could drastically improve the flow characteristics and performance of
      the range hood by consuming less energy.

PMID- 21071607
TI  - Contact intervals, survival analysis of epidemic data, and estimation of R(0).
AB  - We argue that the time from the onset of infectiousness to infectious contact,
      which we call the "contact interval," is a better basis for inference in epidemic
      data than the generation or serial interval. Since contact intervals can be right
      censored, survival analysis is the natural approach to estimation. Estimates of
      the contact interval distribution can be used to estimate R(0) in both mass
      action and network-based models. We apply these methods to 2 data sets from the
      2009 influenza A(H1N1) pandemic.

PMID- 21071608
TI  - Human beta-defensin 3 promotes NF-kappaB-mediated CCR7 expression and anti
      apoptotic signals in squamous cell carcinoma of the head and neck.
AB  - The microenvironment of aerodigestive cancers contains tumor-promoting
      inflammatory signals often involved in innate immunity. The epithelial
      malignancy, squamous cell carcinoma of the head and neck (SCCHN), is
      characterized by secretion of inflammatory mediators that can promote
      tumorigenesis and lymph node metastasis. Human beta-defensin (hBD) 3 is one such
      antimicrobial mediator of innate immunity produced by squamous epithelial cells
      in response to tissue damage and inflammation. Here, we hypothesized that the
      observed overexpression of hBD3 in SCCHN may have a tumor-promoting effect or
      contribute to nodal metastasis, which has previously been linked to chemokine
      receptor (CCR) 7 overexpression. Indeed, treatment of non-metastatic SCCHN cells
      with hBD3 induced surface CCR7 expression and migration toward its ligand, CCL19.
      The hBD3-induced CCR7 upregulation in SCCHN cells was significantly reduced by
      inhibition of nuclear factor (NF)-kappaB, an inflammatory transcription factor
      known to influence CCR7 expression. Moreover, hBD3 stimulation provided anti
      apoptotic signals to SCCHN cells, as evidenced by tumor resistance to cisplatin
      induced cell death, which was regulated by phosphoinositide-3-kinase/Akt
      activation. Interestingly, the observed hBD3-mediated effects were not dependent
      on G-protein coupled receptors or toll-like receptors, as has been previously
      published, but hBD3 was internalized through endocytosis, allowing intracellular
      signal transduction. Our findings suggest that hBD3 represents a novel NF-kappaB
      regulated mediator of CCR7 expression and anti-apoptotic pathways, which may be
      exploited by developing SCCHN tumors to enhance their survival and metastasis.

PMID- 21071609
TI  - No longer the poor relations.

PMID- 21071610
TI  - CML: how low can you go?

PMID- 21071611
TI  - HIV and DC: hate at first sight.

PMID- 21071612
TI  - Dissecting CD56dim human NK cells.

PMID- 21071613
TI  - Mystery of the missing target.

PMID- 21071614
TI  - Eosinophils are in the swim!

PMID- 21071615
TI  - VWF self-association: more bands for the buck.

PMID- 21071616
TI  - The neural bases for empathy.
AB  - Human empathy relies on the ability to share emotions as well as the ability to
      understand the other's thoughts, desires, and feelings. Recent evidence points to
      2 separate systems for empathy: an emotional system that supports our ability to
      empathize emotionally and a cognitive system that involves cognitive
      understanding of the other's perspective. Converging evidence from neuroimaging
      and lesion studies shows that a neural network that includes the inferior frontal
      gyrus and the inferior parietal lobule is necessary for emotion recognition and
      emotional contagion. On the other hand, the involvement of the ventromedial
      prefrontal cortex, temporoparietal junction, and the medial temporal lobe in self
      reflection and autobiographical memory places these key regions as necessary for
      cognitive empathy. The proposed dissociation between these systems is supported
      by recent neurochemical experiments involving administration of oxytocin as well
      as by ethological, psychiatric, and developmental studies. Finally, although the
      emotional and cognitive systems appear to work independently, every empathic
      response may still evoke both components to some extent, depending on the social
      context.

PMID- 21071617
TI  - Decoding temporal structure in music and speech relies on shared brain resources
      but elicits different fine-scale spatial patterns.
AB  - Music and speech are complex sound streams with hierarchical rules of temporal
      organization that become elaborated over time. Here, we use functional magnetic
      resonance imaging to measure brain activity patterns in 20 right-handed
      nonmusicians as they listened to natural and temporally reordered musical and
      speech stimuli matched for familiarity, emotion, and valence. Heart rate
      variability and mean respiration rates were simultaneously measured and were
      found not to differ between musical and speech stimuli. Although the same
      manipulation of temporal structure elicited brain activation level differences of
      similar magnitude for both music and speech stimuli, multivariate classification
      analysis revealed distinct spatial patterns of brain responses in the 2 domains.
      Distributed neuronal populations that included the inferior frontal cortex, the
      posterior and anterior superior and middle temporal gyri, and the auditory
      brainstem classified temporal structure manipulations in music and speech with
      significant levels of accuracy. While agreeing with previous findings that music
      and speech processing share neural substrates, this work shows that temporal
      structure in the 2 domains is encoded differently, highlighting a fundamental
      dissimilarity in how the same neural resources are deployed.

PMID- 21071618
TI  - Dissecting the mechanisms underlying short-interval intracortical inhibition
      using exercise.
AB  - Recently, 2 physiologically distinct phases of short-interval intracortical
      inhibition (SICI) have been identified, a larger phase at interstimulus interval
      (ISI) 3 ms and a smaller phase at ISI 1 ms. While the former is mediated by
      synaptic processes, the mechanisms underlying the first phase of SICI remain a
      matter of debate. Separately, it is known that fatiguing hand exercise reduces
      SICI, a measure of cortical excitability. Consequently, the present study
      assessed effects of fatiguing hand exercise on the 2 SICI phases, using threshold
      tracking transcranial magnetic stimulation techniques, to yield further
      information on underlying mechanisms. Studies were undertaken on 22 subjects,
      with SICI assessed at baseline, after each voluntary contraction (VC) period of
      120 s and 5, 10, and 20 min after last VC, with responses recorded over abductor
      pollicis brevis. Exercise resulted in significant reduction of SICI at ISI 1 ms
      (SICI(baseline) 9.5 +/- 2.7%; SICI(MAXIMUM REDUCTION) 2.5 +/- 2.5%, P < 0.05) and
      3 ms (SICI(baseline) 16.8 +/- 1.7%; SICI(MAXIMUM REDUCTION) 11.6 +/- 2.1%, P <
      0.05), with the time course of reduction being different for the 2 phases. Taken
      together, findings from the present study suggest that synaptic processes were
      the predominant mechanism underlying the different phases of SICI.

PMID- 21071619
TI  - Performance-related increases in hippocampal N-acetylaspartate (NAA) induced by
      spatial navigation training are restricted to BDNF Val homozygotes.
AB  - Recent evidence indicates experience-dependent brain volume changes in humans,
      but the functional and histological nature of such changes is unknown. Here, we
      report that adult men performing a cognitively demanding spatial navigation task
      every other day over 4 months display increases in hippocampal N-acetylaspartate
      (NAA) as measured with magnetic resonance spectroscopy. Unlike measures of brain
      volume, changes in NAA are sensitive to metabolic and functional aspects of
      neural and glia tissue and unlikely to reflect changes in microvasculature.
      Training-induced changes in NAA were, however, absent in carriers of the Met
      substitution in the brain-derived neurotrophic factor (BDNF) gene, which is known
      to reduce activity-dependent secretion of BDNF. Among BDNF Val homozygotes,
      increases in NAA were strongly related to the degree of practice-related
      improvement in navigation performance and normalized to pretraining levels 4
      months after the last training session. We conclude that changes in demands on
      spatial navigation can alter hippocampal NAA concentrations, confirming
      epidemiological studies suggesting that mental experience may have direct effects
      on neural integrity and cognitive performance. BDNF genotype moderates these
      plastic changes, in line with the contention that gene-context interactions shape
      the ontogeny of complex phenotypes.

PMID- 21071620
TI  - Smoking history and physical performance in midlife: results from the British
      1946 birth cohort.
AB  - BACKGROUND: The adverse effects of smoking on individual medical conditions are
      well known; however, the cumulative effect of smoking on physical performance is
      not well characterized, particularly in midlife. METHODS: In the British 1946
      Birth Cohort Study, cigarette pack-years were examined with standing balance,
      chair rising, grip strength, and an overall composite index. Pack-years were
      calculated from data collected at ages 20, 25, 31, 36, 43, and 53 years, whereas
      physical performance, cognitive function, anthropometry, and spirometry were
      assessed at age 53 years in 2,394 men and women. Regression and cubic splines
      were used to assess the relationship between pack-years and physical performance.
      RESULTS: Greater pack-years smoked were associated with lower overall physical
      performance and lower performance in standing balance and chair rising; however,
      there was no association with grip strength. For every 10 pack-years smoked, the
      overall physical performance index decreased by 0.11 SD (95% confidence interval:
      0.07-0.15, p < .001), standing balance time decreased by 0.09 SD (0.05-0.13), and
      the reciprocal of chair rise time decreased by 0.11 SD (0.07-0.16). Adjustment
      for education, social class, lung function, cognitive function, and medical
      conditions attenuated the effect, but pack-years remained significantly
      associated with standing balance and chair rising time. CONCLUSIONS: Lifetime
      cigarette pack-years are strongly related to physical performance in the fifth
      decade of life, suggesting that smokers will enter older adulthood with decreased
      physiological reserve. As smoking prevalence remains high in many developed
      countries and is rapidly growing in developing countries, these findings
      underscore the need for effective smoking cessation and prevention programs.

PMID- 21071621
TI  - The impact of feedback on self-rated driving ability and driving self-regulation
      among older adults.
AB  - In 129 community-dwelling older adults, feedback regarding qualification for an
      insurance discount (based on a visual speed of processing test; Useful Field of
      View) was examined as a prospective predictor of change in self-reported driving
      ability, driving avoidance, and driving exposure over 3 months, along with
      physical, visual, health, and cognitive variables. Multiple regression models
      indicated that after controlling for baseline scores on the outcome measures,
      failure to qualify was a significant predictor of increased avoidance over 3
      months (p = .02) but not change in self-rated driving ability or exposure. Female
      gender (p = .03) was a significant predictor of subsequent lower self-rated
      driving ability. Overall, the findings of this study provide support for the role
      of feedback in the self-monitoring of older adults' driving behavior through
      avoidance of challenging driving situations but not through driving exposure or
      self-rated driving ability.

PMID- 21071622
TI  - Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a
      mouse model of chronic intestinal inflammation.
AB  - Intraepithelial lymphocytes (IELs) represent the first line of lymphocyte defense
      against the intestinal bacteria. Although previous studies have demonstrated a
      protective role of IELs in the development of colitis, the data supporting a
      regulatory role for IELs are limited. The objective of this study was to examine
      the suppressive activity of IELs in vitro and in vivo using a mouse model of
      chronic small and large bowel inflammation. Adoptive transfer of CD8alpha(+) IELs
      isolated from small intestines of wild-type (WT) mice into TCR betaxdelta
      deficient (TCR betaxdelta(-/-)) recipients did not prevent or delay the onset of
      the disease induced by WT CD4(+)CD45RB(high) T cells. On the contrary, we
      observed a more rapid onset of wasting and clinical signs of intestinal
      inflammation when compared with animals injected with CD4(+)CD45RB(high) T cells
      alone. Histopathological scores of small and large bowel did not differ
      significantly between the two groups. Transfer of IELs alone did not produce any
      pathological changes. Real-time PCR analysis of intestinal tissues showed up
      regulation of message for T(h)1- and macrophage-derived cytokines in colon and
      small bowel. Using Foxp3-GFP reporter mice, we were unable to detect any Foxp3(+)
      cells within the CD8alpha(+) IELs but did find a small population of
      Foxp3(+)CD4(+) IELs in the small and large bowel. Using in vitro suppression
      assay, we found that neither TCRalphabeta(+)CD8alphaalpha(+),
      TCRalphabeta(+)CD8alphabeta(+) nor TCRgammadelta(+)CD8alphaalpha(+) IELs were
      capable of suppressing CD4(+) T-cell proliferation. Taken together, our data do
      not support an immunoregulatory role for CD8alpha(+) IELs in a mouse model of
      small and large bowel inflammation.

PMID- 21071623
TI  - Reading achievement in relation to phonological coding and awareness in deaf
      readers: a meta-analysis.
AB  - The relation between reading ability and phonological coding and awareness (PCA)
      skills in individuals who are severely and profoundly deaf was investigated with
      a meta-analysis. From an initial set of 230 relevant publications, 57 studies
      were analyzed that experimentally tested PCA skills in 2,078 deaf participants.
      Half of the studies found statistically significant evidence for PCA skills and
      half did not. A subset of 25 studies also tested reading proficiency and showed a
      wide range of effect sizes. Overall PCA skills predicted 11% of the variance in
      reading proficiency in the deaf participants. Other possible modulating factors,
      such as task type and reading grade level, did not explain the remaining
      variance. In 7 studies where it was measured, language ability predicted 35% of
      the variance in reading proficiency. These meta-analytic results indicate that
      PCA skills are a low to moderate predictor of reading achievement in deaf
      individuals and that other factors, most notably language ability, have a greater
      influence on reading development, as has been found to be the case in the hearing
      population.

PMID- 21071624
TI  - Beliefs about behavior account for age differences in the correspondence bias.
AB  - OBJECTIVES: Older adults tend to exhibit the correspondence bias to a greater
      extent than young adults. The current study examined whether these age
      differences are a function of the degree to which an individual subscribes to a
      lay theory of attitude-behavior consistency. METHODS: First, participants
      responded to questions regarding their beliefs about attitude-behavior
      consistency. Approximately 2 weeks later, 144 (67 young adults and 77 older
      adults) participants completed the correspondence bias task. RESULTS: As
      expected, older adults were more biased than young adults. Analyses revealed that
      the degree to which an individual holds attitude-behavior consistency beliefs in
      the dishonesty domain accounted for age-related differences in the correspondence
      bias. DISCUSSION: The results of this study suggest that age differences in the
      correspondence bias task are in part driven by older adults holding stronger
      attitude-behavior consistency beliefs than young adults.

PMID- 21071625
TI  - Behavioral effects of nicotine withdrawal differ by genetic strain in male and
      female adolescent rats.
AB  - INTRODUCTION: Gender and ethnicity are powerful predictors of initiation and
      maintenance of cigarette smoking in adults but less is known about their role in
      smoking in adolescents. Consistent with human studies, rat models also reveal sex
      and strain differences in response to nicotine administration. METHODS: This
      research examined nicotine withdrawal behaviors in 96 adolescent, male and
      female, Sprague Dawley (SD) and Long Evans (LE) rats. Rats received seven days
      continuous subcutaneous infusion of saline or 3.16 mg/kg nicotine via Alzet
      osmotic minipumps. Behavioral observations were made before, during, and after
      saline or nicotine administration. Occurrences of six specific behaviors were
      quantified: abnormal posture or movement, abnormal grooming, whole-body shakes,
      ptosis, empty-mouth chewing/teeth chattering, and diarrhea. RESULTS: SD male and
      female rats that received nicotine displayed significantly more withdrawal
      behaviors 1 and 2 days after cessation of nicotine administration compared with
      rats that had received saline. LE male rats that received nicotine displayed
      significantly more withdrawal behaviors 1 day but not 2 days after cessation of
      nicotine administration compared with males that received saline. LE females
      showed no significant withdrawal behaviors after cessation of nicotine
      administration. CONCLUSION: Results indicate that nicotine withdrawal in
      adolescent rats depends on sex and strain.

PMID- 21071626
TI  - Histamine regulates autoreactive T cell activation and adhesiveness in inflamed
      brain microcirculation.
AB  - Histamine may contribute to the pathology of MS and its animal model EAE. We
      explored the effects of histamine and specific HR agonists on activation and
      migratory capacity of myelin-autoreactive T cells. We show that histamine in
      vitro inhibits proliferation and IFN-gamma production of mouse T cells activated
      against PLP(139-151). These effects were mimicked by the H1R agonist HTMT and the
      H2R agonist dimaprit and were associated with reduced activation of ERK&frac12;
      kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved
      in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and
      chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked
      firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus
      histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T
      cells and their ability to traffic through the inflamed BBB. Strategies aimed at
      interfering with the histamine axis might have relevance in the therapy of
      autoimmune disease of the CNS.

PMID- 21071627
TI  - Transcriptional control of photosynthesis genes: the evolutionarily conserved
      regulatory mechanism in plastid genome function.
AB  - Chloroplast sensor kinase (CSK) is a bacterial-type sensor histidine kinase found
      in chloroplasts--photosynthetic plastids--in eukaryotic plants and algae. Using a
      yeast two-hybrid screen, we demonstrate recognition and interactions between:
      CSK, plastid transcription kinase (PTK), and a bacterial-type RNA polymerase
      sigma factor-1 (SIG-1). CSK interacts with itself, with SIG-1, and with PTK. PTK
      also interacts directly with SIG-1. PTK has previously been shown to catalyze
      phosphorylation of plastid-encoded RNA polymerase (PEP), suppressing plastid
      transcription nonspecifically. Phospho-PTK is inactive as a PEP kinase. Here, we
      propose that phospho-CSK acts as a PTK kinase, releasing PTK repression of
      chloroplast transcription, while CSK also acts as a SIG-1 kinase, blocking
      transcription specifically at the gene promoter of chloroplast photosystem I.
      Oxidation of the photosynthetic electron carrier plastoquinone triggers
      phosphorylation of CSK, inducing chloroplast photosystem II while suppressing
      photosystem I. CSK places photosystem gene transcription under the control of
      photosynthetic electron transport. This redox signaling pathway has its origin in
      cyanobacteria, photosynthetic prokaryotes from which chloroplasts evolved. The
      persistence of this mechanism in cytoplasmic organelles of photosynthetic
      eukaryotes is in precise agreement with the CoRR hypothesis for the function of
      organellar genomes: the plastid genome and its primary gene products are Co
      located for Redox Regulation. Genes are retained in plastids primarily in order
      for their expression to be subject to this rapid and robust redox regulatory
      transcriptional control mechanism, whereas plastid genes also encode genetic
      system components, such as some ribosomal proteins and RNAs, that exist in order
      to support this primary, redox regulatory control of photosynthesis genes.
      Plastid genome function permits adaptation of the photosynthetic apparatus to
      changing environmental conditions of light quantity and quality.

PMID- 21071628
TI  - Optomechanically induced transparency.
AB  - Electromagnetically induced transparency is a quantum interference effect
      observed in atoms and molecules, in which the optical response of an atomic
      medium is controlled by an electromagnetic field. We demonstrated a form of
      induced transparency enabled by radiation-pressure coupling of an optical and a
      mechanical mode. A control optical beam tuned to a sideband transition of a micro
      optomechanical system leads to destructive interference for the excitation of an
      intracavity probe field, inducing a tunable transparency window for the probe
      beam. Optomechanically induced transparency may be used for slowing and on-chip
      storage of light pulses via microfabricated optomechanical arrays.

PMID- 21071629
TI  - Lynx1, a cholinergic brake, limits plasticity in adult visual cortex.
AB  - Experience-dependent brain plasticity typically declines after an early critical
      period during which circuits are established. Loss of plasticity with closure of
      the critical period limits improvement of function in adulthood, but the
      mechanisms that change the brain's plasticity remain poorly understood. Here, we
      identified an increase in expression of Lynx1 protein in mice that prevented
      plasticity in the primary visual cortex late in life. Removal of this molecular
      brake enhanced nicotinic acetylcholine receptor signaling. Lynx1 expression thus
      maintains stability of mature cortical networks in the presence of cholinergic
      innervation. The results suggest that modulating the balance between excitatory
      and inhibitory circuits reactivates visual plasticity and may present a
      therapeutic target.

PMID- 21071630
TI  - How cats lap: water uptake by Felis catus.
AB  - Animals have developed a range of drinking strategies depending on physiological
      and environmental constraints. Vertebrates with incomplete cheeks use their
      tongue to drink; the most common example is the lapping of cats and dogs. We show
      that the domestic cat (Felis catus) laps by a subtle mechanism based on water
      adhesion to the dorsal side of the tongue. A combined experimental and
      theoretical analysis reveals that Felis catus exploits fluid inertia to defeat
      gravity and pull liquid into the mouth. This competition between inertia and
      gravity sets the lapping frequency and yields a prediction for the dependence of
      frequency on animal mass. Measurements of lapping frequency across the family
      Felidae support this prediction, which suggests that the lapping mechanism is
      conserved among felines.

PMID- 21071631
TI  - A cryptic sulfur cycle in oxygen-minimum-zone waters off the Chilean coast.
AB  - Nitrogen cycling is normally thought to dominate the biogeochemistry and
      microbial ecology of oxygen-minimum zones in marine environments. Through a
      combination of molecular techniques and process rate measurements, we showed that
      both sulfate reduction and sulfide oxidation contribute to energy flux and
      elemental cycling in oxygen-free waters off the coast of northern Chile. These
      processes may have been overlooked because in nature, the sulfide produced by
      sulfate reduction immediately oxidizes back to sulfate. This cryptic sulfur cycle
      is linked to anammox and other nitrogen cycling processes, suggesting that it may
      influence biogeochemical cycling in the global ocean.

PMID- 21071632
TI  - How learning to read changes the cortical networks for vision and language.
AB  - Does literacy improve brain function? Does it also entail losses? Using
      functional magnetic resonance imaging, we measured brain responses to spoken and
      written language, visual faces, houses, tools, and checkers in adults of variable
      literacy (10 were illiterate, 22 became literate as adults, and 31 were literate
      in childhood). As literacy enhanced the left fusiform activation evoked by
      writing, it induced a small competition with faces at this location, but also
      broadly enhanced visual responses in fusiform and occipital cortex, extending to
      area V1. Literacy also enhanced phonological activation to speech in the planum
      temporale and afforded a top-down activation of orthography from spoken inputs.
      Most changes occurred even when literacy was acquired in adulthood, emphasizing
      that both childhood and adult education can profoundly refine cortical
      organization.

PMID- 21071633
TI  - hTERT overexpression alleviates intracellular ROS production, improves
      mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells.
AB  - The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of
      the telomerase holoenzyme. Evidence is accumulating to link hTERT to activities
      other than telomere maintenance and immortalization. Here, we show that hTERT
      overexpression not only reduces the basal cellular reactive oxygen species (ROS)
      levels but also inhibits endogenous ROS production in response to stimuli that
      induce intracellular ROS generation. Conversely, siRNA-mediated gene silencing of
      hTERT potentiated the increase in cellular ROS levels following exposure to
      oxidative stress. This antioxidant effect of hTERT is mediated via a significant
      increase in the ratio of reduced to oxidized glutathione (GSH:GSSG) as well as
      efficient recovery of the oxidized peroxiredoxin to its nonoxidized form. Our
      data also provide evidence for mitochondrial localization of hTERT, and a
      significantly higher activity of cytochrome C oxidase, the rate-limiting enzyme
      in the mitochondrial electron transport chain, in hTERT overexpressing cells. To
      ascertain whether the improved mitochondrial function and antioxidant effect of
      hTERT could provide cancer cells with a survival advantage, the effect of
      oxidative stress on mitochondrial apoptosis was evaluated. Indeed, hTERT
      overexpressing cells inhibited cytosolic acidification, translocation of Bax, the
      drop in mitochondrial transmembrane potential, the release of cytochrome C to the
      cytosol, and cell death. Taken together, these data demonstrate a hitherto
      undefined role of hTERT in alleviating cellular ROS levels by way of potentiating
      the cellular antioxidant defense systems, and in doing so endowing cancer cells
      with the ability to evade death stimuli.

PMID- 21071634
TI  - Next-generation assessments.

PMID- 21071635
TI  - U.S. elections. Researchers anxious and on the defensive after Republican gains.

PMID- 21071637
TI  - U.S. elections. Election means change in climate for efforts to curb emissions.

PMID- 21071636
TI  - Ralph Hall bids to lead science panel.

PMID- 21071638
TI  - U.S. elections. Retiring legislators warn of pitfalls facing science in new
      Congress.

PMID- 21071639
TI  - Cancer screening. The promise and pitfalls of a cancer breakthrough.

PMID- 21071641
TI  - Remote sensing. Earth-observation summit endorses global data sharing.

PMID- 21071640
TI  - Paleoanthropology. Neandertal brain growth shows a head start for moderns.

PMID- 21071642
TI  - Human genetics. Affordable 'exomes' fill gaps in a catalog of rare diseases.

PMID- 21071643
TI  - Scientific gold mine or dicey money pit?

PMID- 21071644
TI  - Archaeology. Collapse? What collapse? Societal change revisited.

PMID- 21071645
TI  - Air pollution. Taking the sting out of acid rain.

PMID- 21071646
TI  - Training physicians to communicate.

PMID- 21071647
TI  - Editorial expression of concern.

PMID- 21071648
TI  - Retraction.

PMID- 21071649
TI  - Mentors for elementary school teachers.

PMID- 21071650
TI  - Birds of prey remain at risk.

PMID- 21071651
TI  - Environment and development. Earth system science for global sustainability:
      grand challenges.

PMID- 21071652
TI  - Medicine. Prion-like behavior of amyloid-beta.

PMID- 21071653
TI  - Materials science. Materials ecology: an industrial perspective.

PMID- 21071654
TI  - Cell biology. Irremediable complexity?

PMID- 21071655
TI  - Plant science. Fertility goddesses as Trojan horses.

PMID- 21071656
TI  - Social science. Cooperation and the commons.

PMID- 21071657
TI  - Chemistry. Glimpsing the critical intermediate in cytochrome P450 oxidations.

PMID- 21071658
TI  - Retrospective. Benoit B. Mandelbrot (1924-2010).

PMID- 21071659
TI  - Amazonia through time: Andean uplift, climate change, landscape evolution, and
      biodiversity.
AB  - The Amazonian rainforest is arguably the most species-rich terrestrial ecosystem
      in the world, yet the timing of the origin and evolutionary causes of this
      diversity are a matter of debate. We review the geologic and phylogenetic
      evidence from Amazonia and compare it with uplift records from the Andes. This
      uplift and its effect on regional climate fundamentally changed the Amazonian
      landscape by reconfiguring drainage patterns and creating a vast influx of
      sediments into the basin. On this "Andean" substrate, a region-wide edaphic
      mosaic developed that became extremely rich in species, particularly in Western
      Amazonia. We show that Andean uplift was crucial for the evolution of Amazonian
      landscapes and ecosystems, and that current biodiversity patterns are rooted deep
      in the pre-Quaternary.

PMID- 21071660
TI  - A wandering mind is an unhappy mind.
AB  - We developed a smartphone technology to sample people's ongoing thoughts,
      feelings, and actions and found (i) that people are thinking about what is not
      happening almost as often as they are thinking about what is and (ii) found that
      doing so typically makes them unhappy.

PMID- 21071661
TI  - Cytochrome P450 compound I: capture, characterization, and C-H bond activation
      kinetics.
AB  - Cytochrome P450 enzymes are responsible for the phase I metabolism of
      approximately 75% of known pharmaceuticals. P450s perform this and other
      important biological functions through the controlled activation of C-H bonds.
      Here, we report the spectroscopic and kinetic characterization of the long-sought
      principal intermediate involved in this process, P450 compound I (P450-I), which
      we prepared in approximately 75% yield by reacting ferric CYP119 with m
      chloroperbenzoic acid. The Mossbauer spectrum of CYP119-I is similar to that of
      chloroperoxidase compound I, although its electron paramagnetic resonance
      spectrum reflects an increase in |J|/D, the ratio of the exchange coupling to the
      zero-field splitting. CYP119-I hydroxylates the unactivated C-H bonds of lauric
      acid [D(C-H) ~ 100 kilocalories per mole], with an apparent second-order rate
      constant of k(app) = 1.1 * 10(7) per molar per second at 4 degrees C. Direct
      measurements put a lower limit of k >= 210 per second on the rate constant for
      bound substrate oxidation, whereas analyses involving kinetic isotope effects
      predict a value in excess of 1400 per second.

PMID- 21071662
TI  - How the CCA-adding enzyme selects adenine over cytosine at position 76 of tRNA.
AB  - CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3'
      end of transfer RNA (tRNA) precursors without using a nucleic acid template.
      Although the mechanism by which cytosine (C) is selected at position 75 of tRNA
      has been established, the mechanism by which adenine (A) is selected at position
      76 remains elusive. Here, we report five cocrystal structures of the enzyme
      complexed with both a tRNA mimic and nucleoside triphosphates under catalytically
      active conditions. These structures suggest that adenosine 5'-monophosphate is
      incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one
      metal-ion mechanism with aspartate 110 functioning as a general base. The
      discrimination against incorporation of cytidine 5'-triphosphate (CTP) at
      position 76 arises from improper placement of the alpha phosphate of the incoming
      CTP, which results from the interaction of C with arginine 224 and prevents the
      nucleophilic attack by the 3' hydroxyl group of cytidine75.

PMID- 21071663
TI  - Radio-frequency association of Efimov trimers.
AB  - The quantum mechanical three-body problem is one of the fundamental challenges of
      few-body physics. When the two-body interactions become resonant, an infinite
      series of universal three-body bound states is predicted to occur, whose
      properties are determined by the strength of the two-body interactions. We used
      radio-frequency fields to associate Efimov trimers consisting of three
      distinguishable fermions. The measurements of their binding energy are consistent
      with theoretical predictions that include nonuniversal corrections.

PMID- 21071664
TI  - Anomalous strength characteristics of tilt grain boundaries in graphene.
AB  - Graphene in its pristine form is one of the strongest materials tested, but
      defects influence its strength. Using atomistic calculations, we find that,
      counter to standard reasoning, graphene sheets with large-angle tilt boundaries
      that have a high density of defects are as strong as the pristine material and,
      unexpectedly, are much stronger than those with low-angle boundaries having fewer
      defects. We show that this trend is not explained by continuum fracture models
      but can be understood by considering the critical bonds in the strained seven
      membered carbon rings that lead to failure; the large-angle boundaries are
      stronger because they are able to better accommodate these strained rings. Our
      results provide guidelines for designing growth methods to obtain sheets with
      strengths close to that of pristine graphene.

PMID- 21071665
TI  - Structure and formation of the lunar farside highlands.
AB  - The formation of the lunar farside highlands has long been an open problem in
      lunar science. We show that much of the topography and crustal thickness in this
      terrain can be described by a degree-2 harmonic. No other portion of the Moon
      exhibits comparable degree-2 structure. The quantified structure of the farside
      highlands unites them with the nearside and suggests a relation between lunar
      crustal structure, nearside volcanism, and heat-producing elements. The farside
      topography cannot be explained by a frozen-in tidal bulge. However, the farside
      crustal thickness and the topography it produces may have been caused by spatial
      variations in tidal heating when the ancient crust was decoupled from the mantle
      by a liquid magma ocean, similar to Europa's present ice shell.

PMID- 21071666
TI  - Coupling of nitrous oxide and methane by global atmospheric chemistry.
AB  - Nitrous oxide (N(2)O) and methane (CH(4)) are chemically reactive greenhouse
      gases with well-documented atmospheric concentration increases that are
      attributable to anthropogenic activities. We quantified the link between N(2)O
      and CH(4) emissions through the coupled chemistries of the stratosphere and
      troposphere. Specifically, we simulated the coupled perturbations of increased
      N(2)O abundance, leading to stratospheric ozone (O(3)) depletion, altered solar
      ultraviolet radiation, altered stratosphere-to-troposphere O(3) flux, increased
      tropospheric hydroxyl radical concentration, and finally lower concentrations of
      CH(4). The ratio of CH(4) per N(2)O change, -36% by mole fraction, offsets a
      fraction of the greenhouse effect attributable to N(2)O emissions. These CH(4)
      decreases are tied to the 108-year chemical mode of N(2)O, which is nine times
      longer than the residence time of direct CH(4) emissions.

PMID- 21071667
TI  - Effects of rapid global warming at the Paleocene-Eocene boundary on neotropical
      vegetation.
AB  - Temperatures in tropical regions are estimated to have increased by 3 degrees  to
      5 degrees C, compared with Late Paleocene values, during the Paleocene-Eocene
      Thermal Maximum (PETM, 56.3 million years ago) event. We investigated the
      tropical forest response to this rapid warming by evaluating the palynological
      record of three stratigraphic sections in eastern Colombia and western Venezuela.
      We observed a rapid and distinct increase in plant diversity and origination
      rates, with a set of new taxa, mostly angiosperms, added to the existing stock of
      low-diversity Paleocene flora. There is no evidence for enhanced aridity in the
      northern Neotropics. The tropical rainforest was able to persist under elevated
      temperatures and high levels of atmospheric carbon dioxide, in contrast to
      speculations that tropical ecosystems were severely compromised by heat stress.

PMID- 21071668
TI  - Conditional cooperation and costly monitoring explain success in forest commons
      management.
AB  - Recent evidence suggests that prosocial behaviors like conditional cooperation
      and costly norm enforcement can stabilize large-scale cooperation for commons
      management. However, field evidence on the extent to which variation in these
      behaviors among actual commons users accounts for natural commons outcomes is
      altogether missing. Here, we combine experimental measures of conditional
      cooperation and survey measures on costly monitoring among 49 forest user groups
      in Ethiopia with measures of natural forest commons outcomes to show that (i)
      groups vary in conditional cooperator share, (ii) groups with larger conditional
      cooperator share are more successful in forest commons management, and (iii)
      costly monitoring is a key instrument with which conditional cooperators enforce
      cooperation. Our findings are consistent with models of gene-culture coevolution
      on human cooperation and provide external validity to laboratory experiments on
      social dilemmas.

PMID- 21071669
TI  - Conserved molecular components for pollen tube reception and fungal invasion.
AB  - During sexual reproduction in flowering plants such as Arabidopsis, a tip-growing
      pollen tube (PT) is guided to the synergid cells of the female gametophyte, where
      it bursts and releases the two sperm. Here we show that PT reception and powdery
      mildew (PM) infection, which involves communication between a tip-growing hypha
      and a plant epidermal cell, share molecular components. NORTIA (NTA), a member of
      the MLO family originally discovered in the context of PM resistance, and FERONIA
      (FER), a receptor-like kinase, both control PT reception in synergids. Homozygous
      fer mutants also display PM resistance, revealing a new function for FER and
      suggesting that conserved components, such as FER and distinct MLO proteins, are
      involved in both PT reception and PM infection.

PMID- 21071670
TI  - Optogenetic control of cardiac function.
AB  - The cardiac pacemaker controls the rhythmicity of heart contractions and can be
      substituted by a battery-operated device as a last resort. We created a
      genetically encoded, optically controlled pacemaker by expressing halorhodopsin
      and channelrhodopsin in zebrafish cardiomyocytes. Using patterned illumination in
      a selective plane illumination microscope, we located the pacemaker and simulated
      tachycardia, bradycardia, atrioventricular blocks, and cardiac arrest. The
      pacemaker converges to the sinoatrial region during development and comprises
      fewer than a dozen cells by the time the heart loops. Perturbation of the
      activity of these cells was entirely reversible, demonstrating the resilience of
      the endogenous pacemaker. Our studies combine optogenetics and light-sheet
      microscopy to reveal the emergence of organ function during development.

PMID- 21071671
TI  - Contact network structure explains the changing epidemiology of pertussis.
AB  - The epidemiology of whooping cough (pertussis) remains enigmatic. A leading cause
      of infant mortality globally, its resurgence in several developed nations-
      despite the availability and use of vaccines for many decades--has caused alarm.
      We combined data from a singular natural experiment and a detailed contact
      network study to show that age-specific contact patterns alone can explain shifts
      in prevalence and age-stratified incidence in the vaccine era. The practical
      implications of our results are notable: Ignoring age-structured contacts is
      likely to result in misinterpretation of epidemiological data and potentially
      costly policy missteps.

PMID- 21071673
TI  - Catalyzing transdisciplinary studies in public health: a college health survey
      and data platform.
AB  - Researchers, educators, and service providers recognize that health behaviors and
      conditions are interdependent, yet they are too often addressed compartmentally.
      This "silo" approach is unfortunate because it leads to inefficiencies and less
      effective approaches to prevention. This article describes a process designed to
      promote better understanding of the interrelatedness of health behaviors and
      outcomes through a multidimensional Internet-based health survey aimed at
      undergraduate college students. In addition, we describe a data-sharing platform
      whereby faculty and students from across disciplines may access the raw data for
      a variety of uses. An analysis is performed illustrating a syndemic between binge
      drinking, sexually transmitted diseases, and using alcohol or drugs prior to
      sexual intercourse. Potential applications of the multidomain survey are
      discussed, as well as lessons learned and limitations of this approach.

PMID- 21071672
TI  - Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor
      GPR124.
AB  - The orphan G protein-coupled receptor (GPCR) GPR124/tumor endothelial marker 5 is
      highly expressed in central nervous system (CNS) endothelium. Here, we show that
      complete null or endothelial-specific GPR124 deletion resulted in embryonic
      lethality from CNS-specific angiogenesis arrest in forebrain and neural tube.
      Conversely, GPR124 overexpression throughout all adult vascular beds produced CNS
      specific hyperproliferative vascular malformations. In vivo, GPR124 functioned
      cell-autonomously in endothelium to regulate sprouting, migration, and
      developmental expression of the blood-brain barrier marker Glut1, whereas in
      vitro, GPR124 mediated Cdc42-dependent directional migration to forebrain
      derived, vascular endothelial growth factor-independent cues. Our results
      demonstrate CNS-specific angiogenesis regulation by an endothelial receptor and
      illuminate functions of the poorly understood adhesion GPCR subfamily. Further,
      the functional tropism of GPR124 marks this receptor as a therapeutic target for
      CNS-related vascular pathologies.

PMID- 21071674
TI  - Hydrophobic nanoparticles improve permeability of cell-encapsulating
      poly(ethylene glycol) hydrogels while maintaining patternability.
AB  - Cell encapsulating poly(ethylene glycol) hydrogels represent a promising approach
      for constructing 3D cultures designed to more closely approximate in vivo tissue
      environment. Improved strategies are needed, however, to optimally balance
      hydrogel permeability to support metabolic activities of encapsulated cells,
      while maintaining patternability to restore key aspects of tissue architecture.
      Herein, we have developed one such strategy incorporating hydrophobic
      nanoparticles to partially induce looser cross-linking density at the particle
      hydrogel interface. Strikingly, our network design significantly increased
      hydrogel permeability, while only minimally affecting the matrix mechanical
      strength or prepolymer viscosity. This structural advantage improved viability
      and functions of encapsulated cells and permitted micron-scale structures to
      control over spatial distribution of incorporated cells. We expect that this
      design strategy holds promise for the development of more advanced artificial
      tissues that can promote high levels of cell metabolic activity and recapitulate
      key architectural features.

PMID- 21071675
TI  - Cell-free fusion of bacteria-containing phagosomes with endocytic compartments.
AB  - Uptake of microorganisms by professional phagocytic cells leads to formation of a
      new subcellular compartment, the phagosome, which matures by sequential fusion
      with early and late endocytic compartments, resulting in oxidative and
      nonoxidative killing of the enclosed microbe. Few tools are available to study
      membrane fusion between phagocytic and late endocytic compartments in general and
      with pathogen-containing phagosomes in particular. We have developed and applied
      a fluorescence microscopy assay to study fusion of microbe-containing phagosomes
      with different-aged endocytic compartments in vitro. This revealed that fusion of
      phagosomes containing nonpathogenic Escherichia coli with lysosomes requires Rab7
      and SNARE proteins but not organelle acidification. In vitro fusion experiments
      with phagosomes containing pathogenic Salmonella enterica serovar Typhimurium
      indicated that reduced fusion of these phagosomes with early and late endocytic
      compartments was independent of endosome and cytosol sources and, hence, a
      consequence of altered phagosome quality.

PMID- 21071676
TI  - HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest
      and positively regulate viral replication.
AB  - Viral infectivity factor, an accessory protein encoded in the HIV-1 genome,
      induces G2 cell cycle arrest; however, the biological significance and
      mechanism(s) remain totally unclear. Here we demonstrate that the TP53 pathway is
      involved in Vif-mediated G2 cell cycle arrest. Vif enhances the stability and
      transcriptional activity of TP53 by blocking the MDM2-mediated ubiquitination and
      nuclear export of TP53. Furthermore, Vif causes G2 cell cycle arrest in a TP53
      dependent manner. HXB2 Vif lacks these activities toward TP53 and cannot induce
      G2 cell cycle arrest. Using mutagenesis, we demonstrate that the critical
      residues for this function are located in the N-terminal region of Vif. Finally,
      we construct a mutant NL4-3 virus with an NL4-3/HXB2 chimeric Vif defective for
      the ability to induce cell cycle arrest and show that the mutant virus replicates
      less effectively than the wild-type NL4-3 virus in T cells expressing TP53. These
      data imply that Vif induces G2 cell cycle arrest through functional interaction
      with the TP53/MDM2 axis and that the G2 cell cycle arrest induced by Vif has a
      positive effect on HIV-1 replication. This report demonstrates the molecular
      mechanisms and the biological significance of Vif-mediated G2 cell cycle arrest
      for HIV-1 infection.

PMID- 21071677
TI  - skNAC, a Smyd1-interacting transcription factor, is involved in cardiac
      development and skeletal muscle growth and regeneration.
AB  - Cardiac and skeletal muscle development and maintenance require complex
      interactions between DNA-binding proteins and chromatin remodeling factors. We
      previously reported that Smyd1, a muscle-restricted histone methyltransferase, is
      essential for cardiogenesis and functions with a network of cardiac regulatory
      proteins. Here we show that the muscle-specific transcription factor skNAC is the
      major binding partner for Smyd1 in the developing heart. Targeted deletion of
      skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with
      ventricular hypoplasia and decreased cardiomyocyte proliferation that were
      similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle
      specific transcription factor down-regulated in hearts lacking Smyd1, also
      depended on the presence of skNAC. Viable skNAC(-/-) adult mice had reduced
      postnatal skeletal muscle growth and impaired regenerative capacity after
      cardiotoxin-induced injury. Satellite cells isolated from skNAC(-/-) mice had
      impaired survival compared with wild-type littermate satellite cells. Our results
      indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion
      and regulates postnatal skeletal muscle growth and regeneration in mice.

PMID- 21071678
TI  - MtNOA1/RIF1 modulates Medicago truncatula-Sinorhizobium meliloti nodule
      development without affecting its nitric oxide content.
AB  - AtNoa1/Rif1 (formerly referred to as AtNos1) has been shown to modulate nitric
      oxide (NO) content in Arabidopsis. As NO generation in the legume-rhizobium
      symbiosis has been shown, the involvement of an AtNoa1/Rif1 orthologue from
      Medicago truncatula (MtNoa1/Rif1) during its symbiotic interaction with
      Sinorhizobium meliloti has been studied. The expression of MtNoa1/Rif1 appeared
      to occur mainly in nodule vascular bundles and the meristematic zone. Using an
      RNA interference strategy, transgenic roots exhibiting a significantly decreased
      level of MtNoa1/Rif1 expression were analysed. NO production was assessed using a
      fluorescent probe, and the symbiotic capacities of the composite plants upon
      infection with Sinorhizobium meliloti were determined. The decrease in
      MtNoa1/Rif1 expression level resulted in a decrease in NO production in roots,
      but not in symbiotic nodules, indicating a different regulation of NO synthesis
      in these organs. However, it significantly lowered the nodule number and the
      nitrogen fixation capacity of the functional nodules. Although having no
      influence on NO production in nodules, MtNOA1/RIF1 significantly affected the
      establishment and the functioning of the symbiotic interaction. The impairment of
      plastid functioning may explain this phenotype.

PMID- 21071679
TI  - Loss of rachis cell viability is associated with ripening disorders in grapes.
AB  - Rachises of grape (Vitis vinifera L.) clusters that appeared healthy or displayed
      symptoms of the ripening disorders berry shrivel (BS) or bunch-stem necrosis
      (BSN) were treated with the cellular viability stain fluorescein diacetate and
      examined by confocal microscopy. Clusters with BS and BSN symptoms experienced a
      decrease of cell viability throughout the rachis, and their berries contained 70
      80% less sugar than healthy berries. The xylem-mobile dye basic fuchsin,
      infiltrated via the cut base of shoots with one healthy and one BS cluster, moved
      to all berries on the healthy cluster but generally failed to move into the
      peduncle of the BS cluster. Peduncle girdling did not interrupt dye movement in
      the xylem, but stopped solute accumulation in berries and led to berry shrinkage.
      In contrast, surgically destroying the peduncle xylem at the onset of ripening
      did not affect berry growth and solute accumulation. These results indicate that
      cessation of sugar and water accumulation in BS and BSN is associated with phloem
      death in the rachis. Although xylem flow to the berries may also cease, a
      functional xylem connection to the shoot may not be required for normal ripening,
      while water loss from berries by transpiration and xylem efflux may explain the
      characteristic berry shrinkage that is associated with these ripening disorders.
      The similarity of internal tissue breakdown in BS and BSN rachises and the
      correlation observed here between the proportion of shrinking berries on a
      cluster and the severity of rachis necrosis suggest that there may be a gradual
      transition between the two ripening disorders. Seeds from healthy and BS clusters
      showed no differences in colour, morphology, weight, viability, and ability to
      germinate, which indicates that the disorder may not appear until seeds are
      mature.

PMID- 21071680
TI  - Endosperm development in Brachypodium distachyon.
AB  - Grain development and its evolution in grasses remains poorly understood, despite
      cereals being our most important source of food. The grain, for which many grass
      species have been domesticated, is a single-seeded fruit with prominent and
      persistent endosperm. Brachypodium distachyon, a small wild grass, is being
      posited as a new model system for the temperate small grain cereals, but little
      is known about its endosperm development and how this compares with that of the
      domesticated cereals. A cellular and molecular map of domains within the
      developing Brachypodium endosperm is constructed. This provides the first
      detailed description of grain development in Brachypodium for the reference
      strain, Bd21, that will be useful for future genetic and comparative studies.
      Development of Brachypodium grains is compared with that of wheat. Notably, the
      aleurone is not regionally differentiated as in wheat, suggesting that the
      modified aleurone region may be a feature of only a subset of cereals. Also, the
      central endosperm and the nucellar epidermis contain unusually prominent cell
      walls that may act as a storage material. The composition of these cell walls is
      more closely related to those of barley and oats than to those of wheat.
      Therefore, although endosperm development is broadly similar to that of temperate
      small grain cereals, there are significant differences that may reflect its
      phylogenetic position between the Triticeae and rice.

PMID- 21071682
TI  - Decreasing prevalence of oral cleft live births in the Netherlands, 1997-2006.
AB  - OBJECTIVES: The number of new oral cleft patients has fallen in the Netherlands.
      This may be explained by two hypotheses: (1) greater prenatal detection of
      congenital anomalies has led to more pregnancy terminations and (2) increased
      folic acid use has reduced the oral cleft risk. Both hypotheses would mainly
      apply to the category cleft lip/alveolus +/- cleft palate (CL+/-P), since, unlike
      cleft palate only (CP), CL+/-P can be detected prenatally by two-dimensional (2D)
      ultrasound and develops during the period recommended for folic acid use. The
      authors aimed to determine trends in prevalence over 1997-2006 and to evaluate
      the hypotheses by stratifying trends by cleft category. METHODS: This study was a
      time-trend analysis of infants born alive with oral clefts in the Netherlands
      during 1997-2006 and registered in the national oral cleft registry. The authors
      calculated prevalence rates and the estimated annual percentage change (EAPC) for
      all oral clefts and the two categories. RESULTS: In 1997-2006, 3308 infants out
      of 1 970 872 live births had oral clefts, an overall prevalence per 10 000 live
      births of 16.8 (CL+/-P: 11.3; CP: 5.5). Time-trend analysis showed that the
      prevalence of all oral clefts decreased (EAPC -1.8%; 95% CI: -3.0% to -0.6%), as
      did the CL+/-P prevalence (EAPC -2.3%; 95% CI: -3.8% to -0.9%). No significant
      trends were found for the CP prevalence. CONCLUSIONS: Because the live-birth
      prevalence of CL+/-P decreased, that of all oral clefts decreased. These findings
      are in line with both hypotheses and may therefore have implications for prenatal
      counselling and folic acid policy.

PMID- 21071681
TI  - Existing branches correlatively inhibit further branching in Trifolium repens:
      possible mechanisms.
AB  - In Trifolium repens removal of any number of existing branches distal to a nodal
      root stimulates development of axillary buds further along the stem such that the
      complement of branches distal to a nodal root remains constant. This study aimed
      to assess possible mechanisms by which existing branches correlatively inhibit
      the outgrowth of axillary buds distal to them. Treatments were applied to basal
      branches to evaluate the roles of three postulated inhibitory mechanisms: (I) the
      transport of a phloem-mobile inhibitory feedback signal from branches into the
      main stem; (II) the polar flow of auxin from branches into the main stem acting
      to limit further branch development; or (III) the basal branches functioning as
      sinks for a net root-derived stimulatory signal (NRS). Results showed that
      transport of auxin, or of a non-auxin phloem-mobile signal, from basal branches
      did not influence regulation of correlative inhibition and were consistent with
      the possibility that the intra-plant distribution of NRS could be involved in the
      correlative inhibition of distal buds by basal branches. This study supports
      existing evidence that regulation of branching in T. repens is dominated by a
      root-derived stimulatory signal, initially distributed via the xylem, the
      characterization of which will progress the generic understanding of branching
      regulation.

PMID- 21071683
TI  - Mask leak in one-person mask ventilation compared to two-person in newborn infant
      manikin study.
AB  - AIM: To compare a new two-person method (four hands) of delivering mask
      ventilation with a standard one-person method using the Laerdal self-inflating
      bag (SIB) and the Neopuff (NP) infant resuscitator in a manikin model.
      BACKGROUND: Recent studies of simulated neonatal resuscitation using bag and mask
      ventilation techniques have shown facemask leak levels of 55-57% in expert hands.
      METHODS: 48 participants were randomly paired and instructed to give mask
      ventilation for a 2-min period as single-person resuscitators, then as two-person
      paired resuscitators at set pressures for NP and set parameters for SIB. Airway
      pressure, flow, inspiratory tidal volume, expiratory tidal volume and mask leak
      were recorded. RESULTS: A total of 21 578 inflations were recorded and analysed.
      For SIB, mask leak was greater (11.5%) with single-person compared to two-person
      (5.4%; mean difference 6.1%, 95% CI 1.5 to 10.7, p<0.01). For NP, mask leak was
      greater for single-person (22.2%) compared to two-person (9.1%; mean difference
      13.1% 95% CI 3.6 to 22.6, p<0.01). For single-person mask ventilation, mask leak
      was greater with NP (22.2%) compared to SIB (11.5%; mean difference 10.7%, 95% CI
      1.4 to 19.7, p<0.01). For two-person mask ventilation, mask leak was greater for
      NP (9.1%) compared to SIB (5.4%; mean difference 3.7%, 95% CI 0.1 to 6.4,
      p<0.05). CONCLUSIONS: Two-person mask ventilation technique reduces mask leak by
      approximately 50% compared to the standard one-person mask ventilation method. NP
      mask ventilation has higher mask leak than Laerdal SIB for both single- and two
      person technique mask ventilation.

PMID- 21071684
TI  - Troponin T, N-terminal pro natriuretic peptide and a patent ductus arteriosus
      scoring system predict death before discharge or neurodevelopmental outcome at 2
      years in preterm infants.
AB  - BACKGROUND: There is little consensus regarding the use of echocardiography in
      patent ductus arteriosus (PDA) treatment in preterm infants. The use of troponin
      T (cTnT) and N-terminal Pro-BNP (NTpBNP) in combination with echocardiography
      assessment may facilitate the development of a superior predictive model.
      OBJECTIVE: To investigate the ability of cTnT, NTpBNP and a PDA scoring system
      applied at 48 h of life to predict death before discharge and neurodevelopmental
      outcome at 2 years of age. DESIGN/METHODS: Infants <32 weeks and <1500 g were
      prospectively enrolled. Echocardiography evaluation coupled with cTnT and NTpBNP
      measurements were done at 48 h. The ductus arteriosus was scored (0-6) according
      to echocardiography markers of haemodynamic significance. Infants were assessed
      at 2 years using the Bayley scales and categorised into two groups: Severe
      Disability/Death before discharge or Normal/Mild Disability. RESULTS: Sixty
      infants with a median gestation of 27.7 weeks (26.2-29.4) and a median birth
      weight of 1.01 kg (0.86-1.22) were followed up to 2 years of age. Plasma cTnT and
      NTpBNP were higher in the Severe Disability/Death compared to the Normal/Mild
      Disability group (2.30 MUg/l vs 0.19 MUg/l, p<0.001; 9209 pmol/l vs 1664 pmol/l,
      p<0.001, respectively). The severe group had a higher PDA score compared to the
      mild and normal groups (5 vs 2, p<0.001). CONCLUSION: Blood cTnT, NTpBNP and a
      PDA scoring system at 48 h may facilitate the identification of those infants
      with a PDA, who are at greatest risk of poor neurodevelopmental outcome at 2
      years of age.

PMID- 21071685
TI  - Recombinant human interleukin-11 treatment enhances collateral vessel growth
      after femoral artery ligation.
AB  - OBJECTIVE: To investigate the role of recombinant human interleukin-11 (rhIL-11)
      on in vivo mobilization of CD34(+)/vascular endothelial growth factor receptor
      (VEGFR) 2(+) mononuclear cells and collateral vessel remodeling in a mouse model
      of hindlimb ischemia. METHODS AND RESULTS: We observed that treatment of Sv129
      mice with continuous infusion of 200-MUg/kg rhIL-11 per day led to in vivo
      mobilization of CD34(+)/VEGFR2(+) cells that peaked at 72 hours. Sv129 mice
      pretreated with rhIL-11 for 72 hours before femoral artery ligation showed a 3
      fold increase in plantar vessel perfusion, leading to faster blood flow recovery;
      and a 20-fold increase in circulating CD34(+)/VEGFR2(+) cells after 8 days of
      rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in
      collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4
      fold influx of perivascular CD34(+)/VEGFR2(+) cells after 8 days of therapy.
      Functionally, rhIL-11-treated mice showed better hindlimb appearance and use
      scores when compared with syngeneic mice treated with PBS under the same
      experimental conditions. CONCLUSIONS: These novel findings show that rhIL-11
      promotes in vivo mobilization of CD34(+)/VEGFR2(+) mononuclear cells, enhances
      collateral vessel growth, and increases recovery of perfusion after femoral
      artery ligation. Thus, rhIL-11 has a promising role for development as an
      adjunctive treatment of patients with peripheral vascular disease.

PMID- 21071686
TI  - Influences of aortic motion and curvature on vessel expansion in murine
      experimental aneurysms.
AB  - OBJECTIVE: To quantitatively compare aortic curvature and motion with resulting
      aneurysm location, direction of expansion, and pathophysiological features in
      experimental abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: MRI was
      performed at 4.7 T with the following parameters: (1) 3D acquisition for vessel
      geometry and (2) 2D cardiac-gated acquisition to quantify luminal motion. Male 24
      week-old mice were imaged before and after AAA formation induced by angiotensin
      II (AngII)-filled osmotic pump implantation or infusion of elastase. AngII
      induced AAAs formed near the location of maximum abdominal aortic curvature, and
      the leftward direction of expansion was correlated with the direction of
      suprarenal aortic motion. Elastase-induced AAAs formed in a region of low vessel
      curvature and had no repeatable direction of expansion. AngII significantly
      increased mean blood pressure (22.7 mm Hg, P<0.05), whereas both models showed a
      significant 2-fold decrease in aortic cyclic strain (P<0.05). Differences in
      patterns of elastin degradation and localization of fluorescent signal from
      protease-activated probes were also observed. CONCLUSIONS: The direction of AngII
      aneurysm expansion correlated with the direction of motion, medial elastin
      dissection, and adventitial remodeling. Anterior infrarenal aortic motion
      correlated with medial elastin degradation in elastase-induced aneurysms. Results
      from both models suggest a relationship between aneurysm pathological features
      and aortic geometry and motion.

PMID- 21071687
TI  - TRIB1 and GCKR polymorphisms, lipid levels, and risk of ischemic heart disease in
      the general population.
AB  - OBJECTIVE: The goal of this study was to test whether TRIB1-rs2954029 and GCKR
      rs1260326 associate with lipid levels and risk of ischemic heart disease (IHD)
      and myocardial infarction (MI) in the general population. METHODS AND RESULTS: We
      genotyped >71 000 individuals. Lipid levels were studied cross-sectionally. Risk
      of IHD and MI was examined prospectively, cross-sectionally, and in a case
      control study, and a metaanalysis was performed. TRIB1 TA (50%) and AA (27%)
      versus TT (23%) genotypes were associated with increased levels of triglycerides
      (total increase, +0.16 mmol/L; trend, P<0.001), remnant cholesterol (+0.07
      mmol/L; P<0.001), apolipoprotein B (+5.7 mg/dL; P<0.001), and low-density
      lipoprotein cholesterol (+0.11 mmol/L; P<0.001) and with decreased levels of high
      density lipoprotein cholesterol (-0.04 mmol/L; P<0.001). In metaanalyses of the 3
      studies combined, TRIB1 TA and AA versus TT genotypes were associated with 13%
      (95% CI, 5% to 20%) and 15% (7% to 23%) increased risk of IHD, and 11% (1% to
      21%) and 17% (6% to 30%) increased risk of MI, respectively. Although GCKR CT
      (46%) and TT (14%) versus CC (40%) genotypes had effects on triglycerides (+0.17
      mmol/L; trend, P<0.001), remnant cholesterol (+0.07 mmol/L; P<0.001), and
      apolipoprotein B (+4.6 mg/dL; P<0.001) similar to those of TRIB1, GCKR did not
      influence low-density lipoprotein cholesterol levels or risk of IHD or MI. Risks
      of IHD were similar after stratification for gender, age, body mass index,
      hypertension, diabetes mellitus, smoking, statin use, alcohol intake, and
      physical activity. CONCLUSIONS: In the general population, both TRIB1-rs2954029
      and GCKR-rs1260326 were associated with lipid levels, whereas TRIB1 was also
      associated with increased risk of IHD and MI.

PMID- 21071688
TI  - Influence of apolipoprotein A-I domain structure on macrophage reverse
      cholesterol transport in mice.
AB  - OBJECTIVE: The goal of this study was to determine the influence of
      apolipoprotein A-I (apoA-I) tertiary structure domain properties on the
      antiatherogenic properties of the protein. Two chimeric hybrids with the N
      terminal domains swapped (human-mouse apoA-I and mouse-human apoA-I) were
      expressed in apoA-I-null mice with adeno-associated virus (AAV) and used to study
      macrophage reverse cholesterol transport (RCT) in vivo. METHODS AND RESULTS: The
      different apoA-I variants were expressed in apoA-I-null mice that were injected
      with [H(3)]cholesterol-labeled J774 mouse macrophages to measure RCT.
      Significantly more cholesterol was removed from the macrophages and deposited in
      the feces via the RCT pathway in mice expressing mouse-H apoA-I compared with all
      other groups. Analysis of the individual components of the RCT pathway
      demonstrated that mouse-H apoA-I promoted ATP-binding cassette transporter A1
      mediated cholesterol efflux more efficiently than all other variants, as well as
      increasing the rate of cholesterol uptake into liver cells. CONCLUSIONS: The
      structural domain properties of apoA-I affect the ability of the protein to
      mediate macrophage RCT. Replacement of the N-terminal helix bundle domain in the
      human apoA-I with the mouse apoA-I counterpart causes a gain of function with
      respect to macrophage RCT, suggesting that engineering some destabilization into
      the N-terminal helix bundle domain or increasing the hydrophobicity of the C
      terminal domain of human apoA-I would enhance the antiatherogenic properties of
      the protein.

PMID- 21071689
TI  - Properties of procoagulant platelets: defining and characterizing the
      subpopulation binding a functional prothrombinase.
AB  - OBJECTIVE: The goal of this study was to define and characterize the
      subpopulation of platelets capable of regulating the functional interactions of
      factors Va (FVa) and Xa (FXa) on the thrombin-activated platelet surface. METHODS
      AND RESULTS: Flow cytometric analyses were used to define and characterize
      platelet subpopulations. At a concentration of thrombin known to elicit maximal
      platelet activation, platelet-derived FVa release, and prothrombinase
      assembly/function, only a subpopulation of platelets was positive for FVa and FXa
      binding. An additional subpopulation bound lower levels of FVa but little, if
      any, FXa. Fluorescence microscopy analyses confirmed these data. Phenotypically,
      platelets capable of binding FXa were more highly reticulated and demonstrated
      significantly increased expression of several key adhesion molecules, including P
      selectin, glycoprotein Ibalpha, and integrins alpha(IIb) and beta(3). This
      platelet subpopulation was also defined by the expression of a nondissociable,
      membrane-bound pool of functional platelet-derived FVa, which made up ~35% to 50%
      of the total membrane-bound cofactor. CONCLUSIONS: The ability of activated
      platelets to support thrombin generation is defined by a subpopulation of
      platelets expressing a nondissociable pool of platelet-derived FVa and increased
      adhesive receptor density. This subpopulation is hypothesized to play a
      significant role in regulating both normal hemostasis and pathological thrombus
      formation because the adherent properties of platelets and their ability to mount
      and sustain a procoagulant response are crucial steps in both of these processes.

PMID- 21071690
TI  - Mechanism of outside-in {alpha}IIb{beta}3-mediated activation of human platelets
      by the colonizing Bacterium, Streptococcus gordonii.
AB  - OBJECTIVE: To better understand the mechanism of platelet recruitment and
      activation by Streptococcus gordonii. The oral bacterium Streptococcus gordonii,
      is amongst the most common pathogens isolated from infective endocarditis
      patients, and has the property of being able to activate platelets, leading to
      thrombotic complications. The mechanism of platelet recruitment and activation by
      S. gordonii is poorly understood. METHODS AND RESULTS: Infective endocarditis is
      a bacterial infection of the heart valves that carries a high risk of morbidity
      and mortality. The oral bacterium, S gordonii, is among the most common pathogens
      isolated from patients with infective endocarditis and is able to activate
      platelets, leading to thrombotic complications. Platelets interact with S
      gordonii via glycoprotein Ibalpha- and alpha(IIb)beta(3)-recognizing S gordonii
      surface proteins haemaglutitin salivary antigen (Hsa) and platelet adherence
      protein A, respectively. The inhibition of glycoprotein Ibalpha or
      alpha(IIb)beta(3) using blocking antibodies or deletion of S gordonii Hsa or
      platelet adherence protein A significantly reduces platelet adhesion.
      Immunoreceptor tyrosine-based activation motif (ITAM)-containing proteins have
      recently played a role in transmitting activating signals into platelets.
      Platelet adhesion to immobilized S gordonii resulted in tyrosine phosphorylation
      of the ITAM-bearing receptor, FcgammaRIIa, and phosphorylation of downstream
      effectors (ie, spleen tyrosine kinase [Syk] and phospholipase C [PLC]-gamma2).
      Tyrosine phosphorylation of FcgammaRIIa resulted in platelet-dense granule
      secretion, filopodial and lamellipodial extension, and platelet spreading.
      Inhibition of FcgammaRIIa ablated both dense granule release and platelet
      spreading. CONCLUSIONS: Streptococcus gordonii binding to the
      alpha(IIb)beta(3)/FcgammaRIIa integrin/ITAM signaling complex results in platelet
      activation that likely contributes to the thrombotic complications of infective
      endocarditis.

PMID- 21071691
TI  - The prostaglandin E2 receptor EP4 is expressed by human platelets and potently
      inhibits platelet aggregation and thrombus formation.
AB  - OBJECTIVE: Low concentrations of prostaglandin (PG) E(2) enhance platelet
      aggregation, whereas high concentrations inhibit it. The effects of PGE(2) are
      mediated through 4 G protein-coupled receptors, termed E-type prostaglindin (EP)
      receptor EP1, EP2, EP3, and EP4. The platelet-stimulating effect of PGE(2) has
      been suggested to involve EP3 receptors. Here we analyzed the receptor usage
      relating to the inhibitory effect of PGE(2). METHODS AND RESULTS: Using flow
      cytometry, we found that human platelets expressed EP4 receptor protein. A
      selective EP4 agonist (ONO AE1-329) potently inhibited the platelet aggregation
      as induced by ADP or collagen. This effect could be completely reversed by an EP4
      antagonist, but not by PGI(2), PGD(2), and thromboxane receptor antagonists or
      cyclooxygenase inhibition. Moreover, an EP4 antagonist enhanced the PGE(2)
      induced stimulation of platelet aggregation, indicating a physiological
      antiaggregatory activity of EP4 receptors. The inhibitory effect of the EP4
      agonist was accompanied by attenuated Ca(2+) flux, inhibition of glycoprotein
      IIb/IIIa, and downregulation of P-selectin. Most importantly, adhesion of
      platelets to fibrinogen under flow and in vitro thrombus formation were
      effectively prevented by the EP4 agonist. In this respect, the EP4 agonist
      synergized with acetylsalicylic acid. CONCLUSIONS: These results are suggestive
      of EP4 receptor activation as a novel antithrombotic strategy.

PMID- 21071692
TI  - Enhanced levels of soluble CD40 ligand exacerbate platelet aggregation and
      thrombus formation through a CD40-dependent tumor necrosis factor receptor
      associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway.
AB  - OBJECTIVE: CD40 ligand is a thromboinflammatory molecule that predicts
      cardiovascular events. Platelets constitute the major source of soluble CD40
      ligand (sCD40L), which has been shown to influence platelet activation, although
      its exact functional impact on platelets and the underlying mechanisms remain
      undefined. We aimed to determine the impact and the signaling mechanisms of
      sCD40L on platelets. METHODS AND RESULTS: sCD40L strongly enhances platelet
      activation and aggregation. Human platelets treated with a mutated form of sCD40L
      that does not bind CD40, and CD40(-/-) mouse platelets failed to elicit such
      responses. Furthermore, sCD40L stimulation induces the association of the tumor
      necrosis factor receptor-associated factor-2 with platelet CD40. Notably, sCD40L
      primes platelets through activation of the small GTPase Rac1 and its downstream
      target p38 mitogen-activated protein kinase, which leads to platelet shape change
      and actin polymerization. Moreover, sCD40L exacerbates thrombus formation and
      leukocyte infiltration in wild-type mice but not in CD40(-/-) mice. CONCLUSIONS:
      sCD40L enhances agonist-induced platelet activation and aggregation through a
      CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38
      mitogen-activated protein kinase signaling pathway. Thus, sCD40L is an important
      platelet primer predisposing platelets to enhanced thrombus formation in response
      to vascular injury. This may explain the link between circulating levels of
      sCD40L and cardiovascular diseases.

PMID- 21071694
TI  - Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion.
AB  - OBJECTIVE: Early recognition of an acute coronary occlusion (ACO) improves
      clinical outcomes. Soluble fms-like tyrosine kinase-1 (sFLT1) is an endothelium
      derived protein induced by hypoxia. We tested whether sFLT1 levels are elevated
      in ACO. METHODS AND RESULTS: Serum sFLT1 levels were measured by enzyme-linked
      immunosorbent assay in patients with ST-segment elevations and angiographically
      confirmed ACO, unstable angina/non ST-segment elevation myocardial infarction,
      and 2 control groups. To further explore sFLT1 release, a mouse model of ACO and
      in vitro human coronary artery endothelial cell injury were used. sFLT1 levels
      were increased in ACO compared with unstable angina/non-ST-elevation myocardial
      infarction, catheterized controls, or healthy volunteers (200.7+/-15.5 versus
      70.7+/-44.0 versus 10.2+/-4.0 versus 11.7+/-1.7 pg/mL respectively, P<0.001
      versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (>15
      pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of
      creatine kinase levels >10 ng/mL (P<0.01) and 85% had ultrasensitive troponin I
      levels >0.05 ng/mL (P<0.05). Within 60 minutes after symptom onset, sFLT1 was
      more sensitive than the MB isoform of creatine kinase or ultrasensitive troponin
      I for ACO (100% versus 20% versus 20% respectively; P<=0.01 for each). Within 60
      minutes of ACO in mice, sFLT1 levels were elevated. Hypoxia and thrombin
      increased sFLT1 levels within 15 minutes in human coronary artery endothelial
      cells. CONCLUSIONS: sFLT1 levels may be an early indicator of endothelial hypoxia
      in ACO.

PMID- 21071695
TI  - Regulation of functionally active P2Y12 ADP receptors by thrombin in human smooth
      muscle cells and the presence of P2Y12 in carotid artery lesions.
AB  - OBJECTIVE: The platelet P2Y12 ADP receptor is a well-known target of
      thienopyridine-type antiplatelet drugs. This study is the first to describe
      increased transcriptional expression of a functionally active P2Y12 in response
      to thrombin in human vascular smooth muscle cells (SMC). METHODS AND RESULTS: On
      exposure to thrombin, P2Y12 mRNA was transiently increased, whereas total protein
      and cell surface expression of P2Y12 were markedly increased within 6 hours and
      remained elevated over 24 hours. This effect was mediated by activation of
      nuclear factor kappaB. Preincubation with thrombin significantly enhanced the
      efficacy of the P2Y receptor agonist 2-methylthio-ADP to induce interleukin 6
      expression and SMC mitogenesis. Effects induced by 2-methylthio-ADP were
      prevented by RNA interference-mediated knockdown of P2Y12 and a selective P2Y12
      antagonist R-138727, the active metabolite of prasugrel. In addition, positive
      P2Y12 immunostaining was shown in SMC of human carotid artery plaques and was
      found to colocalize with tissue factor, the rate-limiting factor of thrombin
      formation in vivo. CONCLUSIONS: These data suggest that the P2Y12 receptor not
      only is central to ADP-induced platelet activation but also may mediate platelet
      independent responses, specifically under conditions of enhanced thrombin
      formation, such as local vessel injury and atherosclerotic plaque rupture.

PMID- 21071693
TI  - Compartmentalized connexin 43 s-nitrosylation/denitrosylation regulates
      heterocellular communication in the vessel wall.
AB  - OBJECTIVE: To determine whether S-nitrosylation of connexins (Cxs) modulates gap
      junction communication between endothelium and smooth muscle. METHODS AND
      RESULTS: Heterocellular communication is essential for endothelium control of
      smooth muscle constriction; however, the exact mechanism governing this action
      remains unknown. Cxs and NO have been implicated in regulating heterocellular
      communication in the vessel wall. The myoendothelial junction serves as a conduit
      to facilitate gap junction communication between endothelial cells and vascular
      smooth muscle cells within the resistance vasculature. By using isolated vessels
      and a vascular cell coculture, we found that Cx43 is constitutively S
      nitrosylated on cysteine 271 because of active endothelial NO synthase
      compartmentalized at the myoendothelial junction. Conversely, we found that
      stimulation of smooth muscle cells with the constrictor phenylephrine caused Cx43
      to become denitrosylated because of compartmentalized S-nitrosoglutathione
      reductase, which attenuated channel permeability. We measured S
      nitrosoglutathione breakdown and NO(x) concentrations at the myoendothelial
      junction and found S-nitrosoglutathione reductase activity to precede NO release.
      CONCLUSIONS: This study provides evidence for compartmentalized S
      nitrosylation/denitrosylation in the regulation of smooth muscle cell to
      endothelial cell communication.

PMID- 21071696
TI  - P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils
      in mouse and human sickle cell disease.
AB  - OBJECTIVE: To determine the role of platelets in stimulating mouse and human
      neutrophil activation and pulmonary injury in sickle cell disease (SCD). METHODS
      AND RESULTS: Both platelet and neutrophil activation occur in SCD, but the
      interdependence of these events is unknown. Platelet activation and binding to
      leukocytes were measured in mice and patients with SCD and in controls. Relative
      to controls, blood obtained from mice or patients with SCD contained
      significantly elevated platelet-neutrophil aggregates (PNAs). Both platelets and
      neutrophils found in sickle PNAs were activated. Multispectral imaging
      (ImageStream) and conventional flow cytometry revealed a subpopulation of
      activated neutrophils with multiple adhered platelets that expressed
      significantly more CD11b and exhibited greater oxidative activity than single
      neutrophils. On average, wild-type and sickle PNAs contained 1.1 and 2.6
      platelets per neutrophil, respectively. Hypoxia/reoxygenation induced a further
      increase in PNAs in mice with SCD and additional activation of both platelets and
      neutrophils. The pretreatment of mice with SCD with clopidogrel or P-selectin
      antibody reduced the formation of PNAs and neutrophil activation and decreased
      lung vascular permeability. CONCLUSIONS: Our findings suggest that platelet
      binding activates neutrophils and contributes to a chronic inflammatory state and
      pulmonary dysfunction in SCD. The inhibition of platelet activation may be useful
      to decrease tissue injury in SCD, particularly during the early stages of vaso
      occlusive crises.

PMID- 21071697
TI  - Ticagrelor effectively and reversibly blocks murine platelet P2Y12-mediated
      thrombosis and demonstrates a requirement for sustained P2Y12 inhibition to
      prevent subsequent neointima.
AB  - OBJECTIVE: Our goal was to study the effects of ticagrelor on murine platelet
      function and thrombosis and characterize the time course of P2Y(12) inhibition
      required to inhibit neointima formation following vascular injury. METHODS AND
      RESULTS: Mice were treated with ticagrelor or vehicle. Platelet aggregation and P
      selectin expression were assessed over time, and thrombus formation was assessed
      in laser-injured cremasteric arterioles of P2Y(12)+/+ and P2Y(12)-/- mice.
      Neointima formation in FeCl(3)-injured carotid artery was assessed in C57BL/6
      mice treated with different regimens of ticagrelor. Ticagrelor inhibited platelet
      aggregation and P-selectin expression in a dose-dependent, reversible manner.
      Ticagrelor inhibited thrombus formation to the same extent as seen in P2Y(12)-/-
      mice. Neointima formation was markedly reduced in mice treated with ticagrelor
      before and 4 hours after injury (neointima area: control, 39 921+/-22 749 MUm(2),
      versus ticagrelor, 3705+/-2600 MUm(2); P<0.01), whereas administration of
      ticagrelor either before injury only or from 4 hours postinjury was ineffective.
      CONCLUSIONS: Ticagrelor effectively and reversibly inhibits P2Y(12)-mediated
      platelet function and thrombosis in mice. P2Y(12) inhibition is required both at
      the time of and after injury to effectively inhibit neointima formation.
      Additional studies are warranted to evaluate the role of P2Y(12) inhibition in
      preventing restenosis.

PMID- 21071698
TI  - Signaling during platelet adhesion and activation.
AB  - Upon vascular injury, platelets are activated by adhesion to adhesive proteins,
      such as von Willebrand factor and collagen, or by soluble platelet agonists, such
      as ADP, thrombin, and thromboxane A(2). These adhesive proteins and soluble
      agonists induce signal transduction via their respective receptors. The various
      receptor-specific platelet activation signaling pathways converge into common
      signaling events that stimulate platelet shape change and granule secretion and
      ultimately induce the "inside-out" signaling process leading to activation of the
      ligand-binding function of integrin alpha(IIb)beta(3). Ligand binding to integrin
      alpha(IIb)beta(3) mediates platelet adhesion and aggregation and triggers
      "outside-in" signaling, resulting in platelet spreading, additional granule
      secretion, stabilization of platelet adhesion and aggregation, and clot
      retraction. It has become increasingly evident that agonist-induced platelet
      activation signals also cross talk with integrin outside-in signals to regulate
      platelet responses. Platelet activation involves a series of rapid positive
      feedback loops that greatly amplify initial activation signals and enable robust
      platelet recruitment and thrombus stabilization. Recent studies have provided
      novel insight into the molecular mechanisms of these processes.

PMID- 21071699
TI  - Platelets: linking hemostasis and cancer.
AB  - Platelets are the main cellular component in blood responsible for maintaining
      the integrity of the cardiovascular system via hemostasis. Platelet dysfunction
      contributes to a wide range of obvious pathological conditions, such as bleeding
      or thrombosis, but normal platelet function is also linked to diseases not
      immediately associated with hemostasis or thrombosis, such as cancer. Since the
      description of Trousseau syndrome in 1865, various experimental and clinical
      studies have detailed the interaction of platelets with primary tumors and
      circulating metastatic tumor cells. Observations have suggested that platelets
      not only augment the growth of primary tumors via angiogenesis but endow tumor
      cells physical and mechanical support to evade the immune system and extravasate
      to secondary organs, the basis of metastatic disease. Many laboratory and animal
      studies have identified specific targets for antiplatelet therapy that may be
      advantageous as adjuncts to existing cancer treatments. In this review, we
      summarize important platelet properties that influence tumorigenesis, including
      primary tumor growth and metastasis at the molecular level. The studies provide a
      link between the well-studied paradigms of platelet hemostasis and tumorigenesis.

PMID- 21071700
TI  - Regulation of platelet function by class B scavenger receptors in hyperlipidemia.
AB  - Platelets constitutively express class B scavenger receptors CD36 and SR-BI, 2
      closely related pattern recognition receptors best known for their roles in
      lipoprotein and lipid metabolism. The biological role of scavenger receptors in
      platelets is poorly understood. However, in vitro and in vivo data suggest that
      class B scavenger receptors modulate platelet function and contribute
      significantly to thrombosis by sensing pathological or physiological ligands,
      inducing prothrombotic signaling, and increasing platelet reactivity. Platelet
      CD36 recognizes a novel family of endogenous oxidized choline phospholipids that
      accumulate in plasma of hyperlipidemic mice and in plasma of subjects with low
      high-density lipoprotein levels. This interaction leads to the activation of
      specific signaling pathways and promotes platelet activation and thrombosis.
      Platelet SR-BI, on the other hand, plays a critical role in the induction of
      platelet hyperreactivity and accelerated thrombosis under conditions associated
      with increased platelet cholesterol content. Intriguingly, oxidized high-density
      lipoprotein, an SR-BI ligand, can suppress platelet function. These recent
      findings demonstrate that platelet class B scavenger receptors play roles in
      thrombosis in dyslipidemia and may contribute to acute cardiovascular events in
      vivo in hypercholesterolemia.

PMID- 21071701
TI  - Platelet-leukocyte interactions in cardiovascular disease and beyond.
AB  - Platelet-leukocyte interactions define a basic cell process that is characterized
      by the exchange of signals between platelets and different types of leukocytes
      and that bridges 2 fundamental pathophysiological events: atherothrombosis and
      inflammatory immune reactions. When this process takes place at the site of
      atherosclerotic plaque development or at the site of endothelial injury, platelet
      dependent leukocyte recruitment and activation contributes to the inflammatory
      reaction of the vessel wall, which accounts for the exacerbation of
      atherosclerosis and for intimal hyperplasia and plaque instability. Moreover,
      platelet-leukocyte interactions may have a key role in modulating a wide array of
      responses of both the innate and adaptive immune systems, thus contributing to
      the pathogenesis of inflammatory diseases and tissue damage, as well as to host
      defense.

PMID- 21071702
TI  - Protein kinase C upregulates intercellular adhesion molecule-1 and leukocyte
      endothelium interactions in hyperglycemia via activation of endothelial expressed
      calpain.
AB  - OBJECTIVE: We tested the hypothesis of a role for the calcium-dependent protease
      calpain in the endothelial dysfunction induced by hyperglycemic activation of
      protein kinase C (PKC). METHODS AND RESULTS: Chronic hyperglycemia with insulin
      deficiency (type 1 diabetes) was induced in rats by streptozotocin. Total PKC and
      calpain activities, along with activity and expression level of the 2 endothelial
      expressed calpains isoforms, MU- and m-calpain, were measured in vascular tissue
      homogenates by enzymatic assays and Western blot analysis, respectively.
      Intravital microscopy was used to measure and correlate leukocyte-endothelium
      interactions with calpain activity in the microcirculation. Expression levels and
      endothelial localization of the inflammatory adhesion molecule intercellular
      adhesion molecule-1 were studied by Western blot analysis and immunofluorescence,
      respectively. The mechanistic role of hyperglycemia alone in the process of PKC
      induced calpain activation and actions was also investigated. We found that in
      the type 1 diabetic vasculature, PKC selectively upregulates the activity of the
      MU-calpain isoform. Mechanistic studies confirmed a role for hyperglycemia and
      PKCbeta in this process. The functional implications of PKC-induced calpain
      activation were upregulation of endothelial expressed intercellular adhesion
      molecule-1 and leukocyte-endothelium interactions. CONCLUSIONS: Our results
      uncover the role of MU-calpain in the endothelial dysfunction of PKC. Calpain may
      represent a novel molecular target for the treatment of PKC-associated diabetic
      vascular disease.

PMID- 21071703
TI  - Inherited human gp91phox deficiency is associated with impaired isoprostane
      formation and platelet dysfunction.
AB  - OBJECT: Platelet isoprostane 8-ISO-prostaglandin F2alpha (8-iso-PGF2alpha), a
      proaggregating molecule, is believed to derive from nonenzymatic oxidation of
      arachidonic acid. We hypothesized that NADPH is implicated in isoprostane
      formation and platelet activation. METHODS AND RESULTS: We studied 8-iso
      PGF2alpha in platelets from 8 male patients with hereditary deficiency of
      gp91(phox), the catalytic subunit of NADPH oxidase, and 8 male controls. On
      stimulation, platelets from controls produced 8-iso-PGF2alpha, which was
      inhibited -8% by aspirin and -58% by a specific inhibitor of gp91(phox).
      Platelets from patients with gp91(phox) hereditary deficiency had normal
      thromboxane A(2) formation but marked 8-iso-PGF2alpha reduction compared with
      controls. In normal platelets incubated with a gp91(phox) inhibitor or with
      SQ29548, a thromboxane A(2)/isoprostane receptor inhibitor, platelet recruitment,
      an in vitro model of thrombus growth, was reduced by 44% and 64%, respectively; a
      lower effect (-17%) was seen with aspirin. Moreover, thrombus formation under
      shear stress (blood perfusion at the wall shear rate of 1500 s(-1)) was reduced
      in samples in which isoprostane formation was inhibited by NADPH oxidase
      inhibitors. In gp91(phox)-deficient patients, agonist-induced platelet
      aggregation was within the normal range, whereas platelet recruitment was reduced
      compared with controls. Incubation of platelets from gp91(phox)-deficient
      patients with 8-iso-PGF2alpha dose-dependently (1 to 100 pmol/L) increased
      platelet recruitment by mobilizing platelet Ca(2+) and activating gpIIb/IIIa; a
      further increase in platelet recruitment was detected by platelet coincubation
      with l-NAME, an inhibitor of NO synthase. CONCLUSIONS: This study provides the
      first evidence that platelet 8-iso-PGF2alpha maximally derives from gp91(phox)
      activation and contributes to platelet recruitment via activation of gpIIb/IIIa.

PMID- 21071704
TI  - Hepatic hepatocyte nuclear factor 4alpha is essential for maintaining
      triglyceride and cholesterol homeostasis.
AB  - OBJECTIVE: Loss-of-function mutations in human hepatocyte nuclear factor 4alpha
      (HNF4alpha) are associated with maturity-onset diabetes of the young and lipid
      disorders. However, the mechanisms underlying the lipid disorders are poorly
      understood. In this study, we determined the effect of acute loss or augmentation
      of hepatic HNF4alpha function on lipid homeostasis. METHODS AND RESULTS: We
      generated an adenovirus expressing LacZ (Ad-shLacZ) or short hairpin RNA of
      Hnf4alpha (Ad-shHnf4alpha). Tail vain injection of C57BL/6J mice with Ad
      shHnf4alpha reduced hepatic Hnf4alpha expression and resulted in striking
      phenotypes, including the development of fatty liver and a >80% decrease in
      plasma levels of triglycerides, total cholesterol, and high-density lipoprotein
      cholesterol. These latter changes were associated with reduced hepatic
      lipogenesis and impaired very-low-density lipoprotein secretion. Deficiency in
      hepatic Hnf4alpha did not affect intestinal cholesterol absorption despite
      decreased expression of genes involved in bile acid synthesis. Consistent with
      the loss-of-function data, overexpression of Hnf4alpha induced numerous genes
      involved in lipid metabolism in isolated primary hepatocytes. Interestingly, many
      of these HNF4alpha-regulated genes were not induced in wild-type mice that
      overexpressed hepatic Hnf4alpha. Because of selective gene regulation, mice
      overexpressing hepatic Hnf4alpha had unchanged plasma triglyceride levels and
      decreased plasma cholesterol levels. CONCLUSIONS: Loss of hepatic HNF4alpha
      results in severe lipid disorder as a result of dysregulation of multiple genes
      involved in lipid metabolism. In contrast, augmentation of hepatic HNF4alpha
      activity lowers plasma cholesterol levels but has no effect on plasma
      triglyceride levels because of selective gene regulation. Our data indicate that
      hepatic HNF4alpha is essential for controlling the basal expression of numerous
      genes involved in lipid metabolism and is indispensable for maintaining normal
      lipid homeostasis.

PMID- 21071705
TI  - A critical role for chloride channel-3 (CIC-3) in smooth muscle cell activation
      and neointima formation.
AB  - OBJECTIVE: We have shown that the chloride-proton antiporter chloride channel-3
      (ClC-3) is required for endosome-dependent signaling by the Nox1 NADPH oxidase in
      SMCs. In this study, we tested the hypothesis that ClC-3 is necessary for
      proliferation of smooth muscle cells (SMCs) and contributes to neointimal
      hyperplasia following vascular injury. METHODS AND RESULTS: Studies were
      performed in SMCs isolated from the aorta of ClC-3-null and littermate control
      (wild-type [WT]) mice. Thrombin and tumor necrosis factor-alpha (TNF-alpha) each
      caused activation of both mitogen activated protein kinase extracellular signal
      regulated kinases 1 and 2 and the matrix-degrading enzyme matrix
      metalloproteinase-9 and cell proliferation of WT SMCs. Whereas responses to
      thrombin were preserved in ClC-3-null SMCs, the responses to TNF-alpha were
      markedly impaired. These defects normalized following gene transfer of ClC-3.
      Carotid injury increased vascular ClC-3 expression, and compared with WT mice,
      ClC-3-null mice exhibited a reduction in neointimal area of the carotid artery 28
      days after injury. CONCLUSIONS: ClC-3 is necessary for the activation of SMCs by
      TNF-alpha but not thrombin. Deficiency of ClC-3 markedly reduces neointimal
      hyperplasia following vascular injury. In view of our previous findings, this
      observation is consistent with a role for ClC-3 in endosomal Nox1-dependent
      signaling. These findings identify ClC-3 as a novel target for the prevention of
      inflammatory and proliferative vascular diseases.

PMID- 21071706
TI  - Platelets: covert regulators of lymphatic development.
AB  - The field of platelet biology has rapidly expanded beyond the classical role of
      platelets in preventing blood loss and orchestrating clot formation. Despite the
      lack of transcriptional ability of these anuclear cell fragments, platelet
      function is now thought to encompass such diverse contexts as tissue repair,
      immune activation, primary tumor formation, and metastasis. Recent studies from
      multiple groups have turned the spotlight on an exciting new role for platelets
      in the formation of lymphatic vessels during embryonic development. Genetic
      experiments demonstrate that podoplanin, a transmembrane protein expressed on
      lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2
      (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet
      activation. When components of this pathway are disrupted, aberrant vascular
      connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null
      embryos manifest identical blood-lymphatic mixing. The identification of
      platelets as the critical cell type mediating blood-lymphatic vascular separation
      raises new questions in our understanding of lymphatic development and platelet
      biology.

PMID- 21071707
TI  - Enhanced foam cell formation, atherosclerotic lesion development, and
      inflammation by combined deletion of ABCA1 and SR-BI in Bone marrow-derived cells
      in LDL receptor knockout mice on western-type diet.
AB  - RATIONALE: macrophages cannot limit the uptake of lipids and rely on cholesterol
      efflux mechanisms for maintaining cellular cholesterol homeostasis. Important
      mediators of macrophage cholesterol efflux are ATP-binding cassette transporter 1
      (ABCA1), which mediates the efflux of cholesterol to lipid-poor apolipoprotein
      AI, and scavenger receptor class B type I (SR-BI), which promotes efflux to
      mature high-density lipoprotein. OBJECTIVE: the aim of the present study was to
      increase the insight into the putative synergistic roles of ABCA1 and SR-BI in
      foam cell formation and atherosclerosis. METHODS AND RESULTS: low-density
      lipoprotein receptor knockout (LDLr KO) mice were transplanted with bone marrow
      from ABCA1/SR-BI double knockout mice, the respective single knockouts, or wild
      type littermates. Serum cholesterol levels were lower in ABCA1/SR-BI double
      knockout transplanted animals, as compared to the single knockout and wild-type
      transplanted animals on Western-type diet. Despite the lower serum cholesterol
      levels, massive foam cell formation was found in macrophages from spleen and the
      peritoneal cavity. Interestingly, ABCA1/SR-BI double knockout transplanted
      animals also showed a major increase in proinflammatory KC (murine interleukin-8)
      and interleukin-12p40 levels in the circulation. Furthermore, after 10 weeks of
      Western-type diet feeding, atherosclerotic lesion development in the aortic root
      was more extensive in the LDLr KO mice reconstituted with ABCA1/SR-BI double
      knockout bone marrow. CONCLUSIONS: deletion of ABCA1 and SR-BI in bone marrow
      derived cells enhances in vivo macrophage foam cell formation and atherosclerotic
      lesion development in LDLr KO mice on Western diet, indicating that under high
      dietary lipid conditions, both macrophage ABCA1 and SR-BI contribute
      significantly to cholesterol homeostasis in the macrophage in vivo and are
      essential for reducing the risk for atherosclerosis.

PMID- 21071708
TI  - Reduction in hexokinase II levels results in decreased cardiac function and
      altered remodeling after ischemia/reperfusion injury.
AB  - RATIONALE: Cardiomyocytes switch substrate utilization from fatty acid to glucose
      under ischemic conditions; however, it is unknown how perturbations in glycolytic
      enzymes affect cardiac response to ischemia/reperfusion (I/R). Hexokinase (HK)II
      is a HK isoform that is expressed in the heart and can bind to the mitochondrial
      outer membrane. OBJECTIVE: We sought to define how HKII and its binding to
      mitochondria play a role in cardiac response and remodeling after I/R. METHODS
      AND RESULTS: We first showed that HKII levels and its binding to mitochondria are
      reduced 2 days after I/R. We then subjected the hearts of wild-type and
      heterozygote HKII knockout (HKII(+/)-) mice to I/R by coronary ligation. At
      baseline, HKII(+/)- mice have normal cardiac function; however, they display
      lower systolic function after I/R compared to wild-type animals. The mechanism
      appears to be through an increase in cardiomyocyte death and fibrosis and a
      reduction in angiogenesis; the latter is through a decrease in hypoxia-inducible
      factor-dependent pathway signaling in cardiomyocytes. HKII mitochondrial binding
      is also critical for cardiomyocyte survival, because its displacement in tissue
      culture with a synthetic peptide increases cell death. Our results also suggest
      that HKII may be important for the remodeling of the viable cardiac tissue
      because its modulation in vitro alters cellular energy levels, O2 consumption,
      and contractility. CONCLUSIONS: These results suggest that reduction in HKII
      levels causes altered remodeling of the heart in I/R by increasing cell death and
      fibrosis and reducing angiogenesis and that mitochondrial binding is needed for
      protection of cardiomyocytes.

PMID- 21071709
TI  - Mesenchymal stem cells express c-kit.

PMID- 21071713
TI  - The role of cGMP-dependent protein kinase in controlling cardiomyocyte cGMP.

PMID- 21071714
TI  - Lipid oxidation and cardiovascular disease: introduction to a review series.

PMID- 21071716
TI  - Biology of endoplasmic reticulum stress in the heart.
AB  - The endoplasmic reticulum (ER) is a multifunctional intracellular organelle
      supporting many processes required by virtually every mammalian cell, including
      cardiomyocytes. It performs diverse functions, including protein synthesis,
      translocation across the membrane, integration into the membrane, folding,
      posttranslational modification including N-linked glycosylation, and synthesis of
      phospholipids and steroids on the cytoplasmic side of the ER membrane, and
      regulation of Ca(2+) homeostasis. Perturbation of ER-associated functions results
      in ER stress via the activation of complex cytoplasmic and nuclear signaling
      pathways, collectively termed the unfolded protein response (UPR) (also known as
      misfolded protein response), leading to upregulation of expression of ER resident
      chaperones, inhibition of protein synthesis and activation of protein
      degradation. The UPR has been associated with numerous human pathologies, and it
      may play an important role in the pathophysiology of the heart. ER stress
      responses, ER Ca(2+) buffering, and protein and lipid turnover impact many
      cardiac functions, including energy metabolism, cardiogenesis,
      ischemic/reperfusion, cardiomyopathies, and heart failure. ER proteins and ER
      stress-associated pathways may play a role in the development of novel UPR
      targeted therapies for cardiovascular diseases.

PMID- 21071715
TI  - Novel lipid mediators promote resolution of acute inflammation: impact of aspirin
      and statins.
AB  - The resolution of acute inflammation is a process that allows for inflamed
      tissues to return to homeostasis. Resolution was held to be a passive process, a
      concept now overturned with new evidence demonstrating that resolution is
      actively orchestrated by distinct cellular events and endogenous chemical
      mediators. Among these, lipid mediators, such as the lipoxins, resolvins,
      protectins, and newly identified maresins, have emerged as a novel genus of
      potent and stereoselective players that counter-regulate excessive acute
      inflammation and stimulate molecular and cellular events that define resolution.
      Given that uncontrolled, chronic inflammation is associated with many
      cardiovascular pathologies, an appreciation of the endogenous pathways and
      mediators that control timely resolution can open new terrain for therapeutic
      approaches targeted at stimulating resolution of local inflammation, as well as
      correcting the impact of chronic inflammation in cardiovascular disorders. Here,
      we overview and update the biosynthesis and actions of proresolving lipid
      mediators, highlighting their diverse protective roles relevant to vascular
      systems and their relation to aspirin and statin therapies.

PMID- 21071717
TI  - WNT signaling in adult cardiac hypertrophy and remodeling: lessons learned from
      cardiac development.
AB  - On pathological stress, the heart reactivates several signaling pathways that
      traditionally were thought to be operational only in the developing heart. One of
      these pathways is the WNT signaling pathway. WNT controls heart development but
      is also modulated during adult heart remodeling. This review summarizes the
      currently available data regarding WNT signaling during left ventricular (LV)
      remodeling. Upstream, soluble frizzled-related proteins (sFRPs) block WNT
      dependent activation of the canonical WNT pathway. By inhibition of WNT
      activation, these factors also reduce beta-catenin-dependent transcription by
      altering the ratio of cytoplasmic/nuclear beta-catenin. In experimental settings,
      sFRPs injected into the heart attenuated LV remodeling. sFRPs are secreted from
      autologous bone marrow-derived mononuclear cells. Disheveled is a signaling
      intermediate of both the canonical and noncanonical WNT pathway. Similarly to the
      effect of sFRP, depletion of a disheveled isoform attenuated LV remodeling. In
      contrast, disheveled activation led to progressive dilated cardiomyopathy.
      Inhibition of nuclear beta-catenin signaling downstream of the canonical WNT
      pathway significantly reduced postinfarct mortality and functional decline of LV
      function following chronic left anterior descending coronary artery ligation. WNT
      signaling also affects mobilization and homing of bone marrow-derived
      vasculogenic progenitor cells. Finally, heart-specific WNT/beta-catenin
      interaction partners have been identified that will possibly allow targeting this
      pathway in a tissue-specific manner. In summary, the WNT pathway plays a pivotal
      role in adult cardiac remodeling and may be suitable for therapeutic
      interventions. Currently, several molecular and cellular mechanisms whereby WNT
      inhibition attenuates LV remodeling are proposed. Reactivation of the
      developmental program to restore functional LV myocardium from resident precursor
      cells may significantly contribute to this process.

PMID- 21071718
TI  - Reduced tongue pressure against the hard palate on the paralyzed side during
      swallowing predicts Dysphagia in patients with acute stroke.
AB  - BACKGROUND AND PURPOSE: Dysphagia is important for prognosis in patients with
      stroke because this condition can cause aspiration pneumonia or nutritional
      deficits. The present study investigated the relationship between tongue motor
      deficits and dysphagia in patients with acute stroke. METHODS: Maximal tongue
      pressure on the hard palate when swallowing 5 mL of water was measured using a T
      shaped sensor sheet with 5 measuring points in 33 dysphagic and 31 nondysphagic
      patients with acute stroke. Maximum tongue pressures at each measuring point were
      compared between dysphagic and nondysphagic groups and between paralyzed and
      nonparalyzed sides. RESULTS: Tongue pressure at each measuring point was
      significantly smaller in dysphagic patients than in nondysphagic patients with
      the largest significant difference on the paralyzed side. The magnitude of tongue
      pressure to predict dysphagia was calculated as 4.6 kPa on the paralyzed side,
      offering 71.4% sensitivity and 72.3% specificity. CONCLUSIONS: Reduced tongue
      pressure on the paralyzed side may predict dysphagia in patients with acute
      stroke.

PMID- 21071719
TI  - Age-period-cohort analysis of stroke incidence in Dijon from 1985 to 2005.
AB  - BACKGROUND AND PURPOSE: Variations in stroke incidence could be explained by
      changes in vascular and environmental factors that affect the risk of stroke and
      changes in risk factors that are present in early life. The aim of this study was
      to identify and measure the effects of 3 interrelated factors, age, calendar
      period of stroke onset, and birth year cohort, on the incidence rates of stroke
      from 1985 through 2005. METHODS: Age-period-cohort models were used to analyze
      stroke incidence in Dijon from 1985 to 2005 from a population-based registry that
      collects data on all stroke patients whatever the type of management, in the
      public hospital, private hospitals, or at home, in the population of Dijon
      (150,000 inhabitants). RESULTS: For ischemic stroke, the incidence rose with time
      in men depending not only on age, but also on the period and cohort effects (P =
      0.017). For women, the incidence only depended on age (P < 0.001; incidence rate
      ratio, 1.085; 95% CI, 1.081 to 1.089). For hemorrhagic stroke, the rise in the
      incidence with time depended only on age in men, whereas in women, it depended on
      age, period, and cohort effects (P = 0.019). CONCLUSIONS: Age, birth cohort, and
      calendar period contain relevant information to define and explain trends in
      stroke incidence rates over a long period.

PMID- 21071720
TI  - Cost of illness in subarachnoid hemorrhage: a German longitudinal study.
AB  - BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is a
      cerebrovascular disease with a high mortality rate and severe disability.
      Longitudinal studies investigating health-economic costs in SAH are scare and
      only one of them analyzed cost-driving factors. The objective was to evaluate
      first-year costs in German patients with aneurysmal SAH and to identify
      independent determinants of costs. METHODS: One hundred thirteen incident cases
      of aneurysmal SAH treated in the Department of Neurosurgery and Neuroradiology at
      the University of Bonn (catchment area of 500,000 people) between January 2004
      and December 2005 were eligible for the study. Cost data were collected using
      health-economic questionnaires applied at baseline and 6- and 12-month follow-up
      time. All costs are expressed in (year 2009 values). Clinical assessments were
      performed using Hunt and Hess scale, Barthel Index, and Rankin Scale. Independent
      cost-driving factors were determined using multiple regression analysis. RESULTS:
      The total first-year costs were 38,300 (95% CI, 34 490 to 43,100) per patient.
      Direct costs accounted for 58.7% of total costs and were mainly paid by the
      health insurance (92.0%). Inpatient costs were the main cost component of direct
      and total costs (42.8% of total costs). The major cost-driving factors of total
      costs were younger age and worse functional outcome at 12-month follow-up
      (Barthel Index). CONCLUSIONS: Aneurysmal SAH is a cerebrovascular disease with
      considerable health-economic burden. Healthcare programs aimed at reducing the
      burden of SAH on society and individuals should consider cost-driving factors of
      SAH. Further health-economic studies investigating cost-driving factors of SAH in
      different countries are needed.

PMID- 21071721
TI  - Body weight, not thrombus-burden tissue plasminogen activator dosing: but still.

PMID- 21071722
TI  - Balloon angioplasty for intracranial atherosclerotic disease: periprocedural
      risks and short-term outcomes in a multicenter study.
AB  - BACKGROUND AND PURPOSE: whether stenting is superior to angioplasty in the
      treatment of intracranial atherosclerotic disease is unknown. Dissections, vessel
      rupture, and lesion recoil observed with primary angioplasty using balloon
      catheters designed for coronary arteries have undermined the role of primary
      angioplasty as a preferred treatment for intracranial atherosclerotic disease.
      The goal of this study is to report the immediate and 3-month outcomes of
      treating patients with intracranial atherosclerotic disease with angioplasty
      balloon catheters in a multicenter study. METHODS: this is a retrospective review
      of 74 patients from 4 institutions treated with primary angioplasty for
      intracranial atherosclerotic disease over a 6-year time period. Technical success
      (residual stenosis <= 50%), periprocedural success (no vascular complication
      within 72 hours), and 3-month outcomes are reported. RESULTS: the mean degree of
      stenosis pretreatment was 79% +/- 14% and reduced to 34% +/- 18% after
      angioplasty. Technical success was achieved in 68 (92%; 95% CI, 83% to 97%) of
      the 74 patients. Periprocedural success was achieved in 65 (88%; 95% CI, 78% to
      94%) of the 74 patients. There were 4 (5%; 95% CI, 1.5% to 13%) major procedure
      related strokes, 2 of which resulted in death within 6 hours of the procedure.
      The 30-day stroke/death rate was 5% (4 of 74; CI, 1.5% to 13%). Three-month
      follow-up was available in 71 patients. In this interval, 2 patients had new
      stroke, 1 in the ipsilateral territory and the other in the contralateral
      territory. The 3-month stroke or death rate was 8.5% (6 of 71; CI, 3.1% to
      17.5%); the retreatment rate was 2.8% (2 of 71; CI, 0.3% to 10%). CONCLUSIONS:
      balloon angioplasty is a relatively safe alternative treatment for intracranial
      atherosclerotic disease. Its role in the long-term secondary prevention of
      recurrent stroke as compared with intracranial stenting and medical therapy
      remains to be determined, preferably in a randomized study.

PMID- 21071723
TI  - Weight approximation in stroke before thrombolysis: the WAIST-Study: a
      prospective observational "dose-finding" study.
AB  - BACKGROUND AND PURPOSE: Because of the narrow therapeutic range for thrombolysis
      in stroke, accurate weight-based dosing is essential for efficacy and safety.
      Stroke patients are frequently incapable to communicate their correct body weight
      (BW). Thus, dosing is often based on BW estimation, which may lead to dosing
      errors. The aim of our study was to evaluate availability of BW information,
      accuracy of estimations, and final dosing of Alteplase (tissue plasminogen
      activator [tPA]) in a routine clinical setting. METHODS: A total of 109
      consecutive intravenous thrombolysis patients were prospectively included in the
      study. Recruitment concluded with 100 complete data sets. Before therapy, BW was
      estimated independently by 2 physicians, 2 emergency nurses, and a
      neuroradiological technical assistant. Patients were weighed, and anthropometric
      measurements for BW approximation were taken. Dosing errors were assessed.
      Clinical outcome was evaluated at 90 days. RESULTS: Of 109 patients, 55 (50.5%)
      were unable to provide information on their BW. Of those, 11 (20%) were
      accompanied by relatives able to give BW information. For all patients,
      estimation errors rates ranged from 20.8% (patient's own estimation) up to 38.2%
      (treating physician) and 42.2% (emergency nurse). Finally, 29 patients received
      an Alteplase dosage diverging >10% from the optimal dose. Twelve were under- and
      17 overdosed. Underdosage was an independent predictor for worse outcome in
      multivariate analysis. CONCLUSIONS: Our study shows that reliable BW data are
      missing for a majority of intravenous thrombolysis patients. Measuring BW before
      administering Alteplase remains challenging. Given dosing errors in one-third of
      patients and the observed impact on outcome, standardized weighing before
      thrombolysis should be considered. Clinical Trial Registration-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01006434.

PMID- 21071724
TI  - Induction of autoimmunity to brain antigens by developmental mercury exposure.
AB  - A.SW mice, which are known to be prone to mercury (Hg)-induced immune nephritis,
      were assessed for their ability to develop autoimmunity to brain antigens after
      developmental exposure to Hg. Maternal drinking water containing subclinical
      doses of 1.25MUM methyl Hg (MeHg) or 50MUM Hg chloride (HgCl(2)) were used to
      evaluate developmental (exposure from gestational day 8 to postnatal day 21)
      induction of immune responses to brain antigens. Only HgCl(2) induced
      autoantibody production; the HgCl(2)-exposed offspring showed an increased number
      of CD4(+) splenic T cells expressing CD25 and V(beta) 8.3 chains, and the brain
      reactive immunoglobulin G (IgG) antibodies were predominantly against nuclear
      proteins (30 and 34 kD). The antibodies were deposited in all brain regions.
      Although male and female A.SW mice exposed to HgCl(2) showed deposition of IgG in
      multiple brain regions, inflammation responses were observed only in the
      cerebellum (CB) of female A.SW mice; these responses were associated with
      increased levels of exploratory behavior. The developmental exposure to MeHg also
      induced inflammation in the CB and increased exploratory behavior of the female
      A.SW mice, but the change did not correlate with increased IgG in the brain.
      Interestingly, the non-Hg-exposed female A.SW mice habituated (adapted to the
      information and/or stimuli of a new environment) more than the male A.SW mice
      during exploratory behavior assessment, and the Hg exposure eliminated the
      habituation (i.e., no changes in behavior with subsequent trials), making the
      female behaviors more like those of the male A.SW mice. Additionally, gender
      differences in A.SW brain cytokine expressions prior to Hg exposure were
      eliminated by the Hg exposure.

PMID- 21071726
TI  - N-methylpurine DNA glycosylase plays a pivotal role in the threshold response of
      ethyl methanesulfonate-induced chromosome damage.
AB  - Genotoxic tolerance to low-level exposure of monofunctional alkylating agents is
      compound specific, with the mechanism pertaining to alkyl-induced genotoxic
      threshold response as yet unknown. N-methylpurine DNA glycosylase (MPG), an
      initiator glycosylase of the base excision repair (BER) pathway, typically
      repairs alkyl-induced DNA adducts, many of which are associated with genomic
      instability and tumorigenic risk. Here we demonstrate the involvement of MPG in
      modulating the genotoxic threshold response induced by the Sn2 alkylating agent
      ethyl methanesulfonate (EMS) and not the Sn1 alkylating agent N-ethyl-N
      nitrosourea (ENU) in human lymphoblastoid cells and suggest the lack of N7
      ethylguanine adduct repair as a key factor attributable to an observed increase
      in EMS-induced chromosome damage. Moreover, an increase in MPG messenger RNA
      expression levels in response to EMS and not ENU doses administered below the low
      observed effect level substantiates the proposed specific involvement of MPG in
      relation to EMS-induced genotoxicity. We further report an unexpected dose
      dependent decrease in the mutation frequency of the MPG-deficient cell line M09B
      when challenged with ENU, a response deemed consequential to a pronounced dose
      dependent increase in the number of apoptotic cells relative to wild type.
      Collectively, these findings implicate the differential involvement of MPG
      directed BER as a primary mechanism of action for the chromosome damage threshold
      response and cytotoxicity induced by alkane sulfonates and N-nitrosourea
      compounds, respectively.

PMID- 21071725
TI  - Arsenic, stem cells, and the developmental basis of adult cancer.
AB  - That chemical insults or nutritive changes during in utero and/or postnatal life
      can emerge as diseases much later in life are now being accepted as a recurring
      phenomenon. In this regard, inorganic arsenic is a multisite human carcinogen
      found at high levels in the drinking water of millions of people, although it has
      been difficult until recently to produce tumors in rodents with this metalloid. A
      mouse transplacental model has been developed where maternal exposure to
      inorganic arsenic either acts as a complete carcinogen or enhances carcinogenic
      response to other agents given subsequently in the offspring, producing tumors
      during adulthood. Similarly, human data now have emerged showing that arsenic
      exposure during the in utero period and/or in early life is associated with
      cancer in adulthood. The mouse arsenic transplacental model produces tumors or
      enhances response to other agents in multiple strains and tissues, including
      sites concordant with human targets of arsenic carcinogenesis. It is now believed
      that cancer often is a stem cell (SC)-based disease, and there is no reason to
      think cancer induced by developmental chemical exposure is any different. Indeed,
      arsenic impacts human SC population dynamics in vitro by blocking exit into
      differentiation pathways and whereby creating more key targets for
      transformation. In fact, during in vitro malignant transformation, arsenic causes
      a remarkable survival selection of SCs, creating a marked overabundance of cancer
      SCs (CSCs) compared with other carcinogens once a cancer phenotype is obtained.
      In addition, skin cancers produced following in utero arsenic exposure in mice
      are highly enriched in CSCs. Thus, arsenic impacts key, long-lived SC populations
      as critical targets to cause or facilitate later oncogenic events in adulthood as
      a possible mechanism of developmental basis of adult disease.

PMID- 21071727
TI  - Triclosan affects thyroid hormone-dependent metamorphosis in anurans.

PMID- 21071728
TI  - Human papillomavirus type 16 e6 gene variations in young Chinese women with
      cervical squamous cell carcinoma.
AB  - Human papillomavirus (HPV) 16 E6 gene mutation is considered an important genetic
      change in cervical lesion progression. To explore the possible association of
      specific HPV16 E6 sequence variations with the development of invasive cervical
      squamous cell carcinoma (SCC) in young women, we examined the distribution of
      HPV16 E6 variants in a Chinese cervical SCC population and analyzed the
      difference between younger patients (<=35 years, n = 50) and older ones (>35ys, n
      = 71). Human papillomavirus type 16 E6 DNA was amplified by polymerase chain
      reaction and sequenced by Sanger fluorescent dye dideoxy-termination method.
      Analysis revealed that the most frequently found variation in this Chinese
      population was the EV (As) lineage (65.45%). In addition, the EV (As) lineage
      seems more common and uniform in younger patients than other lineages, and it may
      be associated with early age at diagnosis of cervical SCC in young women.

PMID- 21071729
TI  - Morphometric characteristics of central retinal artery and vein endothelium in
      the normal human optic nerve head.
AB  - PURPOSE: This study documents the morphometric features of arterial and venous
      endothelia in the different laminar regions of the normal human optic nerve head
      and speculates on the hemodynamic characteristics of the central retinal artery
      (CRA) and central retinal vein (CRV). METHODS: Twenty normal human eyes were
      used. Microcannulation techniques were used to label the cytoskeleton and nuclei
      of endothelial cells in the CRA and CRV, after which images were captured using
      confocal microscopy. Length, width, length-to-width ratio, and area measurements
      were obtained from endothelium and its nuclei. Nucleus position with respect to
      cell apex and direction of blood flow was also quantified. Comparisons were made
      between prelaminar, anterior lamina cribrosa, posterior lamina cribrosa, and
      retrolaminar regions. Venous and arterial endothelial cell morphology was also
      compared. RESULTS: There was significant variation in venous endothelial
      morphology across the different laminar regions; however, no differences were
      found in arterial endothelial characteristics (all P > 0.1065). Significant
      differences were found between arterial and venous endothelium in all laminar
      regions apart from the posterior lamina cribrosa, where only nuclear area (P =
      0.0001) and nucleus position (P = 0.0088) were found to be different.
      CONCLUSIONS: Arterial-like appearance of venous endothelium in the posterior
      lamina cribrosa, where pressure gradient forces are predicted to be greatest and
      CRV luminal diameter is known to be narrowest, implicates this as a site of
      altered hemodynamic stress. Heterogeneity of venous endothelium may have
      relevance for understanding ocular vascular diseases such as central retinal vein
      occlusion.

PMID- 21071730
TI  - Effect of cataract in evaluation of macular pigment optical density by
      autofluorescence spectrometry.
AB  - PURPOSE: To assess the effect of cataract on the evaluation of macular pigment
      optical density (MPOD) in aged patients. METHODS: MPOD was prospectively measured
      using autofluorescence spectrometry before and after cataract surgery. The Lens
      Opacities Classification System III was used to grade the cataracts at baseline.
      RESULTS: Forty-five eyes of 41 subjects, who had no ocular disorders or fundus
      autofluorescence abnormalities except for age-related nuclear cataract, were
      included. Preoperative MPOD was 0.350 +/- 0.117 density unit (DU). Regression
      analysis showed that a higher nuclear color score correlated with lower MPOD (t =
      -2.90, P = 0.0063). The preoperative MPOD prediction formula was MPOD = 0.545 -
      0.069 * nuclear color score. A higher nuclear color score correlated
      significantly with failure to measure the MPOD (chi(2) = 5.08, P = 0.0242). The
      mean postoperative MPOD was 0.600 DU (95% confidence interval [CI], 0.562-0.637),
      which was significantly (P < 0.0001) higher than the preoperative level of 0.350
      DU (95% CI, 0.313-0.388). Regression analysis showed that higher preoperative
      MPOD correlated with higher postoperative MPOD (t = 2.91, P = 0.0061).
      CONCLUSIONS: Cataract, especially its nuclear component, affects MPOD measured by
      autofluorescence spectrometry. Care should be taken when using this method in
      eyes with age-related macular maculopathy and age-related macular degeneration
      and in older patients who may develop these diseases.

PMID- 21071732
TI  - Fixation stability during binocular viewing in patients with age-related macular
      degeneration.
AB  - PURPOSE: The authors examined the fixation stability of patients with age-related
      macular degeneration (AMD) and large interocular acuity differences, testing them
      in monocular and binocular viewing conditions. The relationship between fixation
      stability and visual performance during monocular and binocular viewing was also
      studied. METHODS: Twenty patients with AMD participated. Their monocular and
      binocular distance acuities were measured with the ETDRS charts. Fixation
      stability of the better and worse eye were recorded monocularly with the MP-1
      microperimeter (Nidek Technologies Srl., Vigonza, PD, Italy) and binocularly with
      an EyeLink eye tracker (SR Research Ltd., Mississauga, Ontario, Canada).
      Additional recordings of monocular fixations were obtained with the EyeLink in
      viewing conditions when one eye viewed the target while the fellow eye was
      covered by an infrared filter so it could not see the target. RESULTS: Fixation
      stability of the better eye did not change across viewing conditions. Fixation
      stability of the worse eye was 84% to 100% better in the binocular condition than
      in monocular conditions. Fixation stability of the worse eye was significantly
      larger (P < 0.05) than that of the better eye when recorded monocularly with the
      MP-1 microperimeter. This difference was dramatically reduced in the binocular
      condition but remained marginally significant (95% confidence interval, -0.351 to
      -0.006). For the better eye, there was a moderate relationship between fixation
      stability and visual acuity, both monocular and binocular, in all conditions in
      which this eye viewed the target. CONCLUSIONS: Fixational ocular motor control
      and visual acuity are driven by the better-seeing eye when patients with AMD and
      large interocular acuity differences perform the tasks binocularly.

PMID- 21071731
TI  - A novel mouse model for neurotrophic keratopathy: trigeminal nerve stereotactic
      electrolysis through the brain.
AB  - PURPOSE: To develop a mouse model of neurotrophic keratopathy by approaching the
      trigeminal nerve through the brain and to evaluate changes in corneal cell
      apoptosis and proliferation. METHODS: Six- to 8-week-old male C57BL/6 mice
      underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic
      branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the
      cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the
      procedure, we examined the gross nerve pathology, blink reflex, and
      immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67
      positive proliferating corneal cells were evaluated to detect changes from the
      contralateral normal eye. RESULTS: TSE was confirmed by gross histology of the
      trigeminal nerve and was considered effective if the corneal blink reflex was
      completely abolished. TSE totally abolished the blink reflex in 70% of mice and
      significantly reduced it in the remaining 30%. Animals with absent blink reflex
      were used for subsequent experiments. In these mice, a progressive corneal
      degeneration developed, with thinning of the corneal epithelium and eventually
      perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were
      not recognizable histologically. Seven days after TSE, an increase in cellular
      apoptosis in all the corneal layers and a reduction in proliferation in basal
      epithelial cells were detected consistently in all mice. CONCLUSIONS: TSE was
      able, in most cases, to induce a disease state that reflected clinical
      neurotrophic keratitis without damaging the periocular structures. Moreover,
      corneal denervation led to increased apoptosis and reduced proliferation of
      epithelial cells, formally implicating intact nerve function in regulating
      epithelial survival and turnover.

PMID- 21071733
TI  - Wide-range calibration of corneal backscatter analysis by in vivo confocal
      microscopy.
AB  - PURPOSE: To report intra- and interinstrument calibration methods for corneal
      backscatter analysis by in vivo confocal microscopy. METHODS: Applicability of
      two reference standards was evaluated for corneal backscatter calibration.
      Repeated measurements of four concentrations of AMCO Clear (GFS Chemicals, Inc.,
      Powell, OH) suspension and three transparencies (26%, 49%, and 65%) of
      polymethylmethacrylate (PMMA) slabs were performed to assess image intensity
      acquisition in a wide backscatter range. Intra- and intersession repeatability
      and lot-to-lot variation were determined for both standards. The effect of light
      intensity (LI) variation on image intensity acquisition was evaluated by
      examination of PMMA slabs with nonreference (60% and 80%) and reference (72%)
      LIs. Both reference standards were implemented in the protocol. Intrainstrument
      calibration was verified by measuring three normal corneas with 60%, 72%, and 80%
      LIs. Interinstrument calibration was tested by measuring PMMA slabs on a second,
      similar confocal microscope. RESULTS: AMCO Clear was used to express image
      intensity in absolute scatter units (SU), whereas the 49% transparent PMMA slab
      showed best repeatability, without image saturation, to adjust for LI variation.
      Intrainstrument calibration for LI variation reduced mean differences from -38.3%
      to 1.7% (60% LI) and from 33.9% to -0.6% (80% LI). The mean difference between
      similar microscopes decreased from 18.4% to 1.2%, after calibration of the second
      microscope. CONCLUSIONS: Large interinstrument differences necessitate
      calibration of corneal backscatter measurements. With AMCO Clear suspension and
      PMMA slabs, standardization was achieved in a wide backscatter range
      corresponding to normal and opaque corneas. These methods can easily be applied
      in ophthalmic practice.

PMID- 21071734
TI  - Visual acuity development of children with infantile nystagmus syndrome.
AB  - PURPOSE: Infantile nystagmus syndrome (INS) can be idiopathic or associated with
      ocular or systemic disease. The ocular oscillation of INS directly contributes to
      loss of visual acuity. In this study, visual acuity development in patients with
      INS was examined. METHODS: Children with INS were classified as having idiopathic
      INS (n = 84) or INS with an associated sensory deficit: INS and albinism (n =
      71), bilateral optic nerve hypoplasia (ONH; n = 23), or congenital retinal
      disorder (n = 36). Visual acuity was assessed with Teller cards and/or optotypes,
      and the data were analyzed for three age groups (<24 months, 24-48 months, and
      >48 months). RESULTS: Patients with idiopathic INS showed mildly reduced visual
      acuity early in life and gradual maturation with age that paralleled a normative
      curve. Patients with albinism also showed a mild visual deficit early in life but
      failed to keep pace with the normative curve, showing a gradual increase in
      visual acuity deficit. Patients with ONH and congenital retinal disorders
      exhibited more severe visual acuity deficits during infancy. The ONH group
      displayed slow improvement of visual acuity with a plateau at 24 months through
      >48 months, with a small increase in visual acuity deficit. The congenital
      retinal disorder group had no significant change in visual acuity across age and
      had a rapid increase in visual acuity deficit. CONCLUSIONS: The pattern of visual
      acuity development differs among children with INS, depending on the presence or
      absence of associated sensory system deficits. Careful characterization of visual
      system differences in patients with INS is important if visual acuity is an
      outcome in clinical trials.

PMID- 21071735
TI  - Assessment of the contribution of cytokine plasma levels to detect retinopathy of
      prematurity in very low birth weight infants.
AB  - PURPOSE: To prospectively study the association of high cytokine plasma levels
      with later development of retinopathy of prematurity (ROP) in preterm infants
      with early-onset sepsis to assess a laboratory test to detect ROP. METHODS: A
      prospective cohort study was conducted of preterm infants with clinical early
      onset sepsis whose birth weight (BW) was <=1500 g and gestational age (GA) was
      <=32 weeks. Plasma samples were assayed for cytokines IL-6, IL-8, IL-10, IL
      1beta, and TNF-alpha. ROP was diagnosed in screening assessments. For the
      univariate analysis of the known risk factors for ROP, all infants without ROP
      were designated as the No ROP group, patients with any stage of ROP formed the
      ROP group, and all treated patients formed the Severe ROP group. The best cutoff
      points for all cytokine levels were determined by ROC curves. RESULTS: Seventy
      four patients were enrolled. Mean GA and BW were 29.6 +/- 2.1 weeks and 1110.3 +/
      232.5 g, respectively; 49 patients (66.2%) had no ROP and 25 (33.8%) had any
      stage of ROP (17 had stage 1 or 2 ROP and 8 had stage 3 ROP). IL-6 >357 pg/mL, IL
      8 >216 pg/mL, and TNF-alpha >245 pg/mL were significantly associated with
      treatable ROP. CONCLUSIONS: There is a relationship between high plasma levels of
      IL-6, IL-8, and TNF-alpha in the first days of life with the later development of
      ROP severe enough to treat in preterm infants with early-onset sepsis. Further
      epidemiologic studies are needed to explore other possible associations of high
      serum levels of cytokines with ROP in this population at high risk.

PMID- 21071736
TI  - Immunohistochemical evidence of synaptic retraction, cytoarchitectural
      remodeling, and cell death in the inner retina of the rat model of oygen-induced
      retinopathy (OIR).
AB  - PURPOSE: Postnatal exposure to hyperoxia destroys the plexiform layers of the
      neonatal rat retina, resulting in significant electroretinographic anomalies. The
      purpose of this study was to identify the mechanisms at the origin of this loss.
      METHODS: Sprague-Dawley (SD) and Long Evans (LE) rats were exposed to hyperoxia
      from birth to postnatal day (P) 6 or P14 and from P6 to P14, after which rats
      were euthanatized at P6, P14, or P60. RESULTS: At P60, synaptophysin staining
      confirmed the lack of functional synaptic terminals in SD (outer plexiform layer
      [OPL]) and LE (OPL and inner plexiform layer [IPL]) rats. Uneven staining of ON
      bipolar cell terminals with mGluR6 suggests that their loss could play a role in
      OPL thinning. Protein kinase C(PKC)-alpha and recoverin (rod and cone ON-bipolar
      cells, respectively) showed a lack of dendritic terminals in the OPL with
      disorganized axonal projections in the IPL. Although photoreceptor nuclei
      appeared intact, a decrease in bassoon staining (synaptic ribbon terminals)
      suggests limited communication to the inner retina. Findings were significantly
      more pronounced in LE rats. An increase in TUNEL-positive cells was observed in
      LE (inner nuclear layer [INL] and outer nuclear layer [ONL]) and SD (INL) rats
      after P0 to P14 exposure (425.3%, 102.2%, and 146.3% greater than control,
      respectively [P < 0.05]). CONCLUSIONS: Results suggest that cell death and
      synaptic retraction are at the root of OPL thinning. Increased TUNEL-positive
      cells in the INL confirm that cells die, at least in part, because of apoptosis.
      These findings propose a previously undescribed mechanism of cell death and
      synaptic retraction that are likely at the origin of the functional consequences
      of hyperoxia.

PMID- 21071737
TI  - Revealing Henle's fiber layer using spectral domain optical coherence tomography.
AB  - PURPOSE: Spectral domain optical coherence tomography (SD-OCT) uses infrared
      light to visualize the reflectivity of structures of differing optical properties
      within the retina. Despite their presence on histologic studies, traditionally
      acquired SD-OCT images are unable to delineate the axons of photoreceptor nuclei,
      Henle's fiber layer (HFL). The authors present a new method to reliably identify
      HFL by varying the entry position of the SD-OCT beam through the pupil. METHODS:
      Fifteen eyes from 11 subjects with normal vision were prospectively imaged using
      1 of 2 commercial SD-OCT systems. For each eye, the entry position of the SD-OCT
      beam through the pupil was varied horizontally and vertically. The reflectivity
      of outer retinal layers was measured as a function of beam position, and
      thicknesses were recorded. RESULTS: The reflectivity of HFL was directionally
      dependent and increased with eccentricity on the side of the fovea opposite the
      entry position. When HFL was included in the measurement, the thickness of the
      outer nuclear layer (ONL) of central horizontal B-scans increased by an average
      of 52% in three subjects quantified. Four cases of pathology, in which
      alterations to the normal macular geometry affected HFL intensity, were
      identified. CONCLUSIONS: The authors demonstrated a novel method to distinguish
      HFL from true ONL. An accurate measurement of the ONL is critical to clinical
      studies measuring photoreceptor layer thickness using any SD-OCT system.
      Recognition of the optical properties of HFL can explain reflectivity changes
      imaged in this layer in association with macular pathology.

PMID- 21071738
TI  - The effect of ageing on in vivo human ciliary muscle morphology and
      contractility.
AB  - PURPOSE: To assess the effect of ageing on in vivo human ciliary muscle
      morphology and contractility during accommodation. METHODS: Seventy-nine
      subjects, aged 19-70 years were recruited. High-resolution images were acquired
      of nasal and temporal ciliary muscle in the relaxed state, and at stimulus
      vergence levels of -4 and -8 D, using anterior segment optical coherence
      tomography (AS-OCT). Objective refractions and axial lengths were also recorded.
      Linear regression analysis was performed to determine the effect of age on nasal
      and temporal ciliary muscle morphologic characteristics. RESULTS: Ciliary muscle
      anterior length decreased significantly with age both nasally (R = 0.461, P =
      0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of
      37 participants, ciliary muscle maximum width increased significantly with age,
      by 2.8 MUm/year nasally (R = 0.54, P < 0.001) and 3.0 MUm/year temporally (R =
      0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to
      the scleral spur decreased significantly with age on both the nasal and temporal
      aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During
      accommodation, changes to ciliary muscle thickness and length remained constant
      throughout life. CONCLUSIONS: The human ciliary muscle undergoes age-dependent
      changes in morphology that suggest an antero-inwards displacement of muscle mass,
      particularly in emmetropic eyes. However, the morphologic changes observed appear
      not to affect the ability of the muscle to contract during accommodation, even in
      established presbyopes, thus supporting a lenticular model of presbyopia
      development.

PMID- 21071739
TI  - Cone structure in retinal degeneration associated with mutations in the
      peripherin/RDS gene.
AB  - PURPOSE: To study cone photoreceptor structure and function associated with
      mutations in the second intradiscal loop region of peripherin/RDS. METHODS: High
      resolution macular images were obtained with adaptive optics scanning laser
      ophthalmoscopy and spectral domain optical coherence tomography in four patients
      with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of
      retinal structure and fundus autofluorescence (AF) were correlated with visual
      function, including best-corrected visual acuity (BCVA), kinetic and static
      perimetry, fundus-guided microperimetry, full-field electroretinography (ERG),
      and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced
      in each patient. RESULTS: Heterozygous mutations in peripherin/RDS were predicted
      to affect protein structure in the second intradiscal domain in each patient
      (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the
      study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present
      in patient 1, while rod-greater-than-cone dysfunction was present in patient 4;
      macular outer retinal dysfunction was present in all patients. Macular AF was
      heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction
      layer showed increased reflectivity at the fovea in all patients except patient
      1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing
      was significantly increased (z-scores >2) at most locations throughout the
      central 4 degrees  in each patient. CONCLUSIONS: peripherin/RDS mutations
      produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction,
      and increased cone spacing, consistent with cone loss in the macula. The
      abnormalities observed suggest that the integrity of the second intradiscal
      domain of peripherin/RDS is critical for normal macular cone structure.

PMID- 21071740
TI  - Integrin-linked kinase regulates integrin signaling in human trabecular meshwork
      cells.
AB  - PURPOSE: To determine whether integrin-linked kinase (ILK) controls the
      organization of the actin cytoskeleton in the trabecular meshwork (TM) by
      regulating integrin co-signaling. METHODS: The cell binding domain and the
      Heparin II (Hep II) domain of fibronectin were used to activate alpha5beta1 and
      alpha4beta1 integrin signaling, respectively, in differentiated human TM (HTM)
      cells. The role of ILK was determined using either ILK small interfering RNA
      (siRNA) to knockout ILK expression or the ILK inhibitors, KP392 and QLT0267. The
      knockdown of ILK expression was verified by Western blot analysis. The presence
      of actin stress fibers and focal adhesions was determined by labeling cultures
      with phalloidin and anti-talin or ILK antibodies, respectively. RESULTS: Cell
      spreading in differentiated HTM cells required ILK, since ILK siRNA and the ILK
      inhibitors significantly reduced cell spreading, actin polymerization, and the
      localization of talin and ILK in focal adhesions (FAs). Both cell spreading and
      the localization of talin and ILK to FAs in differentiated HTM cells could be
      rescued by inducing alpha4beta1 integrin signaling with a recombinant Hep II
      domain of fibronectin, even though alpha4beta1 integrins were not found in FAs.
      In the absence of ILK inhibition, the Hep II domain had minimal effect on
      alpha5beta1 integrin-mediated spreading. CONCLUSIONS: This study suggests that
      cooperative alpha5beta1/alpha4beta1 integrin signaling may be regulated by ILK
      trans-dominantly and that alterations in ILK activity may affect actin
      cytoskeleton organization and contractility in the TM.

PMID- 21071741
TI  - In vitro interactions of Fusarium and Acanthamoeba with drying residues of
      multipurpose contact lens solutions.
AB  - PURPOSE: To examine in vitro effects of evaporation and drying of multipurpose
      contact lens solutions on survival of Fusarium and Acanthamoeba. METHODS: Conidia
      of representative Fusarium from the 2004-2006 keratitis outbreak and trophozoites
      of Acanthamoeba castellanii were inoculated into commercially available
      multipurpose contact lens care solutions. These solutions were inoculated with
      10(2)-10(6) microbial propagules/mL and were evaporated for at least 24 hours.
      After drying, nutrient media for recovery of surviving organisms were added to
      the residues formed in the lids of 38 mm polystyrene Petri dishes. General
      morphologic patterns of the solution residuals and the distribution and
      morphologies of the microorganisms were recorded with microscopic imaging.
      RESULTS: Various multipurpose contact lens disinfection solutions formed
      distinctive dried residual patterns. Both Fusarium and Acanthamoeba at
      concentrations tested above 10(3) per mL of disinfection solution were recovered
      from dried films with replicate testing. Mature cysts of Acanthamoeba not evident
      in the inocula were observed in sparse numbers in all dried solutions except one
      (Complete Moisture Plus; Advanced Medical Optics) and control salines where
      precysts and mature cysts were common. Both fusaria and amoeba tended to be
      observed in discrete regions of the dried residues. CONCLUSIONS: Regions of
      drying films of multipurpose contact lens disinfection solutions on contact lens
      cases may induce and harbor dormant-resistant stages of Fusarium and
      Acanthamoeba. It is hypothesized that the evaporation and drying of multipurpose
      contact lens disinfection solutions may have been an added risk factor for case
      contamination among Fusarium and Acanthamoeba keratitis patients. The need for
      frequent replacement of contact lens cases is enforced.

PMID- 21071742
TI  - Total corneal power estimation: ray tracing method versus gaussian optics
      formula.
AB  - PURPOSE: To evaluate with the use of corneal topographic data the differences
      between total corneal power calculated using ray tracing (TCP) and the Gaussian
      formula (GEP) in normal eyes, eyes that previously underwent laser in situ
      keratomileusis/photorefractive keratectomy (LASIK/PRK), and theoretical models.
      METHODS: TCP and GEP using mean instantaneous curvature were calculated over the
      central 4-mm zone in 94 normal eyes, 61 myopic-LASIK/PRK eyes, and 9 hyperopic
      LASIK/PRK eyes. A corneal model was constructed to assess the incident angles at
      the posterior corneal surface for both refracted rays and parallel rays. Corneal
      models with varying parameters were also constructed to investigate the
      differences between mean TCP and GEP (4-mm zone), and an optical design software
      validation was performed. RESULTS: The TCP values tended to be less than GEP in
      normal and myopic-LASIK/PRK eyes, with the opposite relationship in some
      hyperopic-LASIK/PRK eyes having the highest anterior surface curvature. The
      difference between TCP and GEP was a function of anterior surface instantaneous
      radii of curvature and posterior/anterior ratio in postrefractive surgery eyes
      but not in normal eyes. In model corneas, posterior incident angles with parallel
      rays were greater than those with refracted rays, producing an overestimation of
      negative effective posterior corneal power; differences in magnitude between TCP
      and GEP increased with decreasing ratio of posterior/anterior radii of curvature,
      consistent with clinical results. CONCLUSIONS: In eyes after refractive surgery,
      calculating posterior corneal power using the Gaussian formula and its paraxial
      assumptions introduces errors in the calculation of total corneal power. This may
      generate errors in intraocular lens power calculation when using the Gaussian
      formula after refractive surgery.

PMID- 21071743
TI  - Differentially expressed genes associated with human limbal epithelial
      phenotypes: new molecules that potentially facilitate selection of stem cell
      enriched populations.
AB  - PURPOSE: The aim of this study was to identify differentially expressed genes in
      the human limbal epithelium by microarray analysis. METHODS: Total RNA isolates
      of human limbal and central corneal epithelia were used after transcription for
      hybridization on whole human genome expression microarrays. A set of
      differentially expressed genes detected by both microarrays was established. In
      the case of eight selected molecules, microarray results were confirmed by qRT
      PCR, and protein expression in the cornea was examined by confocal
      immunofluorescence microscopy. Colocalization with the putative stem cell marker
      C/EBPdelta was also examined. RESULTS: The authors established a database of 126
      limbal overexpressed genes. qRT-PCR confirmed microarray results in all examined
      cases (SPON1, IFITM1, ITM2A, PHLDA1, CXCR4, FZD7, DCT, DKK4). Limbal localization
      of the protein product of SPON1, IFITM1, ITM2A, CXCR4, and DKK4 was shown with
      confocal immunofluorescence microscopy. SPON1, IFITM1, and ITM2A signals mostly
      colocalized with C/EBPdelta-positive putative resting limbal stem cells.
      CONCLUSIONS: By detecting several new differentially expressed genes in the human
      corneal limbus, this study further expands current knowledge on the molecular
      signature of limbal epithelial stem cells. Plasma membrane localization of IFITM1
      and ITM2A suggests their potential usefulness as targets to select stem cell
      enriched populations from the limbal epithelium.

PMID- 21071744
TI  - Potentiating action of propofol at GABAA receptors of retinal bipolar cells.
AB  - PURPOSE: Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is
      known to potentiate GABA(A) receptor activity in a number of CNS neurons and to
      produce changes in electroretinographically recorded responses of the retina.
      However, little is known about propofol's effects on specific retinal neurons.
      The authors investigated the action of propofol on GABA-elicited membrane current
      responses of retinal bipolar cells, which have both GABA(A) and GABA(C)
      receptors. METHODS: Single, enzymatically dissociated bipolar cells obtained from
      rat retina were treated with propofol delivered by brief application in
      combination with GABA or other pharmacologic agents or as a component of the
      superfusing medium. RESULTS: When applied with GABA at subsaturating
      concentrations and with TPMPA (a known GABA(C) antagonist), propofol markedly
      increased the peak amplitude and altered the kinetics of the response. Propofol
      increased the response elicited by THIP (a GABA(A)-selective agonist), and the
      response was reduced by bicuculline (a GABA(A) antagonist). The response to 5
      methyl I4AA, a GABA(C)-selective agonist, was not enhanced by propofol. Serial
      brief applications of (GABA + TPMPA + propofol) led to a progressive increase in
      peak response amplitude and, at higher propofol concentrations, additional
      changes that included a prolonged time course of response recovery. Pre-exposure
      of the cell to perfusing propofol typically enhanced the rate of development of
      potentiation produced by (GABA + TPMPA + propofol) applications. CONCLUSIONS:
      Propofol exerts a marked and selective potentiation on GABA(A) receptors of
      retinal bipolar cells. The data encourage the use of propofol in future studies
      of bipolar cell function.

PMID- 21071745
TI  - Activation of P2X receptors induces apoptosis in human retinal pigment
      epithelium.
AB  - PURPOSE: The retinal pigment epithelium (RPE) is considered a primary site of
      pathology in age-related macular degeneration (AMD), which is the most prevalent
      form of irreversible blindness worldwide in the elderly population. Extracellular
      adenosine triphosphate (ATP) acts as a key signaling molecule in numerous
      cellular processes, including cell death. The purpose of this study was to
      determine whether extracellular ATP induces apoptosis in cultured human RPE.
      METHODS: RPE apoptosis was evaluated by caspase-3 activation, Hoechst staining,
      and DNA fragmentation. Intracellular Ca(2+) levels were determined by both a cell
      based fluorometric Ca(2+) assay and a ratiometric Ca(2+) imaging technique.
      P2X(7) mRNA and protein expression were detected by reverse transcription
      polymerase chain reaction (RT-PCR) and confocal microscopy, respectively.
      RESULTS: The authors found that both the endogenous P2X(7) agonist ATP and the
      synthetic, selective P2X(7) agonist 2',3'-O-(4-benzoylbenzoyl)-ATP (BzATP)
      induced RPE apoptosis, which was significantly inhibited by P2X(7) antagonist
      oxidized ATP (oATP) but not by the P2 receptor antagonist suramin; both ATP and
      BzATP increase intracellular Ca(2+) via extracellular Ca(2+) influx; both ATP-
      and BzATP-induced Ca(2+) responses were significantly inhibited by oATP but not
      by suramin; ATP-induced apoptosis was significantly inhibited or blocked by BAPTA
      AM or by low or no extracellular Ca(2+); and P2X(7) receptor mRNA and protein
      were expressed in RPE cells. CONCLUSIONS: These findings suggest that P2X
      receptors, especially P2X(7) receptors, contribute to ATP- and BzATP-induced
      Ca(2+) signaling and apoptosis in the RPE. Abnormal Ca(2+) homeostasis through
      the activation of P2X receptors could cause the dysfunction and apoptosis of RPE
      that underlie AMD.

PMID- 21071746
TI  - Claudin-19 and the barrier properties of the human retinal pigment epithelium.
AB  - PURPOSE: The retinal pigment epithelium (RPE) separates photoreceptors from
      choroidal capillaries, but in age-related macular degeneration (AMD) capillaries
      breach the RPE barrier. Little is known about human RPE tight junctions or the
      effects of serum on the retinal side of the RPE. METHODS: Cultured human fetal
      RPE (hfRPE) was assessed by the transepithelial electrical resistance (TER) and
      the transepithelial diffusion of methylated polyethylene glycol (mPEG). Claudins
      and occludin were monitored by quantitative RT-PCR, immunoblotting, and
      immunofluorescence. RESULTS: Similar to freshly isolated hfRPE, claudin-19 mRNA
      was 25 times more abundant than claudin-3. Other detectable claudin mRNAs were
      found in even lesser amounts, as little as 3000 times less abundant than claudin
      19. Claudin-1 and claudin-10b were detected only in subpopulations of cells,
      whereas others were undetectable. Knockdown of claudin-19 by small interfering
      RNA (siRNA) eliminated the TER. siRNAs for other claudins had minimal effects.
      Serum affected tight junctions only when presented to the retinal side of the
      RPE. The TER increased 2 times, and the conductance of K(+) relative to Na(+)
      decreased without affecting the permeability of mPEG. These effects correlated
      with increased steady-state levels of occludin. CONCLUSIONS: Fetal human RPE is a
      claudin-19-dominant epithelium that has regional variations in claudin
      expression. Apical serum decreases RPE permeability, which might be a defense
      mechanism that would retard the spread of edema due to AMD.

PMID- 21071748
TI  - A prospective study of macular thickness in amblyopic children with unilateral
      high myopia.
AB  - PURPOSE: To compare macular thickness of the normal fellow eye to that of the
      amblyopic eye using optical coherence tomography (OCT) in children with
      unilateral high myopia. Relationships between macular thickness and magnitude of
      myopic anisometropia, axial length, and visual acuity (VA) were investigated.
      METHODS: Thirty-one children with a mean age of 9.56 years were recruited.
      Macular thickness, axial length, best-corrected VA, and refraction were measured.
      Paired t-test was performed to compare the macular thickness of the amblyopic eye
      to that of the fellow eye. Partial correlations were used to test the
      relationships between interocular difference in macular thickness and
      anisometropia, axial length, and VA. RESULTS: Average (+/- SD) LogMAR VA in the
      amblyopic eye was 0.96 +/- 0.31. Mean spherical equivalent in amblyopic eyes was 
      10.79 +/- 3.40 diopters. A statistically significant difference in macular
      thickness was found between amblyopic and fellow eyes, with amblyopic eyes having
      greater foveal thickness but reduced inner and outer macular thickness. Only the
      nasal outer macular thickness had a statistically significant association with
      the magnitude of anisometropia. CONCLUSIONS: Amblyopic children with unilateral
      high myopia tend to have a thicker fovea and thinner inner and outer macula in
      the amblyopic eye compared to the normal fellow eye. The findings indicate that
      anatomic changes may be present in the retinas of amblyopic children with
      unilateral high myopia. Future study is warranted to determine whether the
      mechanism of the macular changes is due to high myopia, amblyopia, or a
      combination of the two.

PMID- 21071749
TI  - Postrelease specialization and versatility in sexual offenders referred for civil
      commitment.
AB  - Offense specialization and versatility has been explored previously in the prior
      criminal records of sexual offenders. The present study expanded these findings
      by examining offense specialization and versatility in the postrelease offending
      of a sample of sexual offenders referred for civil commitment and released.
      Criminal versatility (not limiting one's offending to sexual crime) both before
      and after commitment was the most commonly observed offending pattern in the
      sample. Specialist offenders (those for whom sexual offenses constituted more
      than half of their total number of previous arrests) were more likely than
      versatile offenders to specialize in sexual offending on release, perhaps
      indicating that specialization is a stable offending tendency. When compared by
      referral status, recidivism records indicated that offenders who were committed
      for treatment were more likely than observed, noncommitted offenders to
      specialize in sexual offending on release. When compared by offender
      classification, child molesters and offenders with mixed aged victims were much
      more likely than rapists and incest offenders to specialize in sexual offending
      on release.

PMID- 21071747
TI  - Effect of elevated intracellular cAMP levels on actomyosin contraction in bovine
      trabecular meshwork cells.
AB  - PURPOSE: Elevated cAMP in the trabecular meshwork (TM) cells increases the
      aqueous humor outflow facility. The authors investigated the mechanisms by which
      elevated cAMP opposes the RhoA-Rho kinase pathway, leading to the relaxation of
      the actomyosin system in bovine TM cells. METHODS: Forskolin (Fsk) and rolipram
      were used to elevate cAMP levels. Changes in the phosphorylation of RhoA at
      Ser188 (a putative inhibitory site), the regulatory light chain of myosin (pMLC),
      and the regulatory subunit of myosin phosphatase (MYPT1) were determined by
      Western blot analysis. The actomyosin contraction was measured by collagen gel
      contraction (CGC) assay. The impact of cAMP on cell-matrix adhesion was followed
      by immunostaining of focal adhesion proteins and by electric cell-substrate
      impedance sensing. RESULTS: Elevated cAMP led to an increase in the
      phosphorylation of RhoA at Ser188, to the inhibition of endothelin-1 (ET-1)
      induced activation of RhoA, and to the formation of stress fibers. The loss of
      pMLC along the stress fibers was comparable to that induced by Y-27632 (Rho
      kinase inhibitor). A concomitant reduction in both MYPT1 phosphorylation and pMLC
      was observed. Elevated cAMP also reduced (ET-1)-induced CGC and the cell
      substrate resistance by >50%. CONCLUSIONS: In TM cells, elevated cAMP leads to
      the phosphorylation of RhoA at Ser188. Consequent inhibition of RhoA activity
      reduces the phosphorylation of MYPT1 at Thr853, leading to a reduction in MLC
      phosphorylation and actomyosin contraction. These actions, similar to those of
      the Rho kinase inhibitors, possibly underlie the reported increase in outflow
      facility in response to Fsk perfusion ex vivo.

PMID- 21071750
TI  - Impact of early surgery on survival of patients with severe mitral regurgitation.
AB  - BACKGROUND: Optimal timing of surgery in degenerative mitral regurgitation (MR)
      remains a controversial topic. The impact of current ACC/AHA guideline
      recommendations about optimal timing of surgery on outcomes is untested and
      contemporary data are lacking. OBJECTIVE: To assess the association between the
      timing of surgery and long-term survival in patients with severe MR. METHODS: A
      cohort of 481 patients with severe, degenerative mitral regurgitation (1995-2007)
      from the Duke Cardiovascular Disease Databank who fulfilled at least one ACC/AHA
      guideline indication for surgery was identified. Exclusion criteria were
      rheumatic disease, congenital mitral valve (MV) disease, hypertrophic
      cardiomyopathy, coronary disease in more than one vessel, endocarditis, other
      severe valve disease, h/o valve repair/replacement. Patients were grouped into
      early surgery (in <= 2 months of presenting with surgical indications) and late
      surgery (>2 months) groups. An adjusted Cox regression model was constructed for
      time to death after 2 months with a time-dependent covariate term for late
      surgery. RESULTS: 168 patients had early surgery (median time to surgery 0.42
      months) with 153 followed up after 2 months, 94 had late surgery (median time to
      surgery 8.75 months) and 219 medically managed. 127/168 in the early surgery
      group and 84/94 in the late surgery group received MV repair (p=0.02). Over 5.6
      years' (median) follow-up there were 35 deaths (21%) in the early surgery group,
      with two occurring before 2 months and 20 (21%) in the late group. In the
      multivariable model, those undergoing early surgery had a lower hazard for death
      than those who underwent late surgery (HR=0.54 (95% CI 0.30 to 0.97), p=0.039).
      MV repair was independently associated with survival (HR=0.45 (95% CI 0.25 to
      0.83), p=0.01). CONCLUSIONS: In patients with severe MR who presented with
      guideline indications for surgery, those selected for earlier surgery had
      improved survival. These data support the current guidelines for early referral
      to surgery in patients with severe MR for enlarged left ventricular dimensions,
      reduced ejection fraction and symptoms rather than delaying surgery. Larger
      randomised trials are needed to definitively answer the question of optimal
      timing of surgery in patients with severe degenerative MR.

PMID- 21071751
TI  - Heart Forecast for cardiovascular risk assessment.

PMID- 21071752
TI  - Neuromuscular transmission is not impaired in axonal Guillain--Barre syndrome.
AB  - BACKGROUND: Previous studies have shown that anti-GQ1b antibodies induce massive
      neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on
      the neuromuscular junction (NMJ) in human limb muscles, this may explain
      selective motor involvement in axonal Guillain--Barre syndrome (GBS). METHODS:
      Axonal-stimulating single-fibre electromyography was performed in the extensor
      digitorum communis muscle of 23 patients with GBS, including 13 with the axonal
      form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies.
      RESULTS: All patients with axonal or demyelinating GBS showed normal or near
      normal jitter, and no blocking. CONCLUSION: In both axonal and demyelinating GBS,
      neuromuscular transmission is not impaired. Our results failed to support the
      hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse
      transmission is presumably impaired in the motor nerve terminal axons proximal to
      the NMJ.

PMID- 21071753
TI  - Use and monitoring of low dose rituximab in myasthenia gravis.
AB  - BACKGROUND: Myasthenia gravis is an autoimmune disorder of the neuromuscular
      junction. Rituximab (RTX), a monoclonal antibody to CD20, leads to B lymphocyte
      depletion and has been used in some autoimmune disorders, including small case
      series of myasthenia gravis patients. METHODS: A retrospective analysis was
      performed of all patients with acetylcholine receptor (AChR) (11 subjects) or
      muscle specific kinase antibody (MuSK) positive myasthenia gravis (three
      subjects), who had been treated with RTX in Brisbane, Australia. In most patients
      1 g of RTX, in two divided doses, was given. Patients were monitored by serial
      clinical assessments, flow cytometry of peripheral blood B lymphocytes and
      antibody testing. RESULTS: RTX led to a significant improvement in symptoms in 11
      of 14 patients. Doses of immunosuppressive medications were able to be reduced in
      12 of 14 patients but medications could be completely ceased in only one patient.
      A demonstrable reduction of autoantibody levels was found in only three AChR
      positive patients and one MuSK positive patient, independent of clinical
      improvement. Peripheral blood B lymphocyte depletion was achieved in 13 out of 14
      patients. B lymphocyte recovery occurred between 9 and 30 months post RTX (median
      12.3 months) and was consistently associated with worsening of clinical symptoms.
      CONCLUSION: Rituximab at a dose of 1 g appears to be beneficial in the treatment
      of patients with severe myasthenia gravis. Serial monitoring of peripheral blood
      B lymphocytes appears to be useful in guiding the need for further RTX therapy.

PMID- 21071754
TI  - A prospective cohort study on severe pain as a risk factor for long-term sickness
      absence in blue- and white-collar workers.
AB  - OBJECTIVE: To estimate the impact of pain in different body regions on future
      long-term sickness absence (LTSA) among blue- and white-collar workers. METHOD:
      Prospective cohort study in a representative sample of 5603 employees (the Danish
      Work Environment Cohort Study) interviewed in 2000, and followed in 2001-2002 in
      a national sickness absence register. Cox regression analysis was performed to
      assess the risk estimates of mutually adjusted severe pain in the neck/shoulder,
      low back, hand/wrist and knees for onset of LTSA, defined as receiving sickness
      absence compensation for at least 3 consecutive weeks. Age, gender, body mass
      index, smoking and diagnosed disease were controlled for. RESULTS: In 2000 the
      prevalence among blue- and white-collar workers, respectively, of severe pain was
      33% and 29% (neck/shoulder), 33% and 25% (low back), 16% and 11% (hand/wrists),
      and 16% and 12% (knees). During 2001-2002, the prevalence of LTSA among blue- and
      white-collar workers was 18% and 12%, respectively. Hand/wrist pain (HR 1.49, 95%
      CI 1.23 to 1.81) and low back pain (HR 1.30, 95% CI 1.11 to 1.53) were
      significant risk factors among the total cohort. Neck/shoulder pain was a
      significant risk factor among white-collar workers only (HR 1.35, 95% CI 1.21 to
      1.85). Knee pain was not a significant risk factor. CONCLUSION: While hand/wrist
      pain and low back pain are general risk factors for LTSA, neck/shoulder pain is a
      specific risk factor among white-collar workers. This study suggests the
      potential for preventing future LTSA through interventions to manage or reduce
      musculoskeletal pain.

PMID- 21071756
TI  - The two-stage clonal expansion model in occupational cancer epidemiology: results
      from three cohort studies.
AB  - OBJECTIVES: The objective of this work was to apply the two-stage clonal
      expansion model, with the intention to expand the literature on epidemiological
      applications of the model and demonstrate the feasibility of incorporating
      biologically based modelling methods into the widely used retrospective cohort
      study. METHODS: The authors fitted the two-stage clonal expansion model model to
      three occupational cohort studies: (1) a cohort of textile workers exposed to
      asbestos and followed for lung cancer mortality; (2) a cohort of diatomaceous
      earth workers exposed to silica and also followed for lung cancer mortality; and
      (3) a cohort of automotive manufacturing workers exposed to straight metalworking
      fluid (MWF) and followed for larynx cancer incidence. The model allowed the
      authors to estimate exposure effects in three stages: cancer initiation (early
      effects), promotion or malignant transformation (late effects). RESULTS: In the
      first cohort, the authors found strong evidence for an early effect of asbestos
      on lung cancer risk. Findings from analyses of the second cohort suggested early
      and less evidently late effects of silica on lung cancer risk. In the MWF (third)
      cohort, there was only weak evidence of straight MWF exposure effects on both
      early and late stages. The authors also observed a late birth cohort effect on
      larynx cancer risk. CONCLUSIONS: The findings for asbestos and silica were
      essentially confirmatory, supporting evidence for their early effects on lung
      cancer from a large body of literature. The effect of straight MWF on larynx
      cancer was less clear.

PMID- 21071755
TI  - Wood dust exposure and risk of lung cancer.
AB  - OBJECTIVES: Despite the compelling association between wood dust and sinonasal
      cancer, there has been little systematic and rigorous study of the relationship
      between wood dust and lung cancer. We investigated whether a history of wood dust
      exposure through occupational and hobby-related activities was associated with
      increased lung cancer risk. METHODS: We conducted a population-based case-control
      study, with 440 cases and 845 age-matched controls. Using detailed work and
      personal histories, quantitative estimates of cumulative exposure to wood dust
      (thought to be primarily from softwood) were calculated for each participant.
      Using unconditional logistic regression adjusted for age and smoking status, risk
      of lung cancer was examined in relation to employment in wood-related
      occupations, working with wood as a hobby, as well as cumulative wood dust
      exposure that took into account both occupational and hobby-related sources.
      RESULTS: While we observed an increased risk of lung cancer associated with
      working in a sawmill (OR=1.5; 95% CI: 1.1, 2.1), we found no evidence of
      increased risks with other occupations, working with wood as a hobby or with
      estimated cumulative exposure to wood dust. Contrary to our hypothesis, we
      observed modest decreased risks with exposure to wood dust, although no dose
      response relationship was apparent. CONCLUSIONS: This study provided somewhat
      reassuring evidence that softwood dust does not increase the risk of lung cancer,
      but future studies should evaluate exposure to hardwood dusts. Suggestive
      evidence for an inverse association may be attributable to the presence of
      endotoxin in the wood dust, but the lack of a dose-response relationship suggests
      a non-causal relationship.

PMID- 21071758
TI  - Management of ocular surface chemical burns.

PMID- 21071757
TI  - Risk factors for progression of subclinical diabetic macular oedema.
AB  - BACKGROUND/AIMS: [corrected] The purpose of this study was to determine the
      incidence of, and risk factors dictating, progression of subclinical macular
      oedema (SCME) to clinically significant macular oedema (CSME) in patients with
      diabetes. METHODS: This was a retrospective, observational case-controlled study
      at the Veterans Administration (VA) Boston Healthcare System. The study group
      included subjects with central subfield macular thickness (CSMT) of 200-300 MUm,
      measured by optical coherence tomography, compared with a control group with
      foveal thickness of <200 MUm, matched for age, sex and duration of diabetes. Main
      outcomes measured were progression to CSME by clinical examination. RESULTS: A
      total 124 eyes of 73 diabetic patients from the greater Boston area were included
      in this retrospective study. The study group comprised 52 eyes of 37 diabetic
      patients with SCME in one or both eyes. The control group included 72 eyes of 36
      patients without macular oedema. Sixteen eyes of 13 subjects (35%) progressed to
      CSME in the study group, compared with six eyes of four subjects (11%) in the
      control group. Stepwise logistic regression analysis confirmed that prior history
      of CSME increased the risk of progression (OR 3.69, CI 1.10 to 12.31, p=0.03).
      Logistic regression analysis also depicted a 15% increase in odds of progression
      with each 10 MUm increase in CSMT (OR 1.15, CI 1.03 to 1.28, p=0.01).
      CONCLUSIONS: The results and statistical analyses of this retrospective study
      suggest that a significant number of patients with SCME ultimately progress to
      CSME compared with controls. A significant association with prior history of
      CSME, advancing age and graded increases in CSMT was found.

PMID- 21071759
TI  - Injectability of silicone oil-based tamponade agents.
AB  - BACKGROUND/AIMS: High viscosity silicone oils are used as tamponade agents to
      increase the resistance to emulsification; however, this makes the oils more
      difficult to inject. Increasing the extensional viscosity is one way to reduce
      emulsification. This study aimed to evaluate how silicone oils with increased
      extensional viscosity behave in terms of their ease of injection. METHODS: The
      shear viscosity and the length of time taken to inject 9 ml of Siluron 1000,
      Siluron 2000, Siluron 5000, SiliconMate, a 56/44 w/w blend of Siluron
      1000/Siluron 5000 (Blend A) and a 90/10 w/w blend of Siluron 1000/PDMS 423kDa
      molecular weight (Blend B) were examined. RESULTS: The shear viscosity of Siluron
      1000, Siluron 2000 and Siluron 5000 were within the expected ranges. The shear
      viscosity of Blend A was 2283 mPa s, Blend B was 4710 mPa s and SiliconMate was
      995.3 mPa s. Siluron 1000 and SiliconMate had the shortest injection times as
      expected due to their lower shear viscosities. Comparison of Siluron 2000 and
      Blend A demonstrated that Siluron 2000 was easier to inject. Similarly, Blend B
      was easier to inject than Siluron 5000. CONCLUSION: Silicone oil blends
      containing small percentages of a high molecular weight additive are easier to
      inject than single grade oils of the equivalent shear viscosity.

PMID- 21071760
TI  - Mycobacterium tuberculosis in donor cornea.

PMID- 21071761
TI  - Warfarin in vitreoretinal surgery: a case controlled series.
AB  - INTRODUCTION: Warfarin is a commonly used anticoagulant whose effect in
      vitreoretinal surgery has not been well studied. METHODS: A series of 60 patients
      on warfarin therapy undergoing pars plana vitrectomy were retrospectively case
      controlled to 60 patients with similar presenting complaints. In addition, an
      online survey was performed of current practice in the UK. RESULTS: 2% of the
      patients receiving vitrectomy were on warfarin. There were 33 males and 27
      females with a median age of 72.5 years; follow-up was for a mean of 0.88 years.
      The international normalised ratio (INR) ranged between 0.94 and 4.6 (median
      2.3). Two cases of suprachoroidal haemorrhages occurred in the control group (one
      with preoperative choroidal haemorrhage from dislocated lens nucleus), while none
      occurred in the warfarin group. 12 patients with rhegmatogenous retinal
      detachment (RRD) in the warfarin group presented with vitreous haemorrhage
      compared with only four in the control group (p=0.04). From the online survey, 48
      respondents (81%) would ask patients to withhold warfarin prior to vitreoretinal
      surgery based on the INR. CONCLUSIONS: There was no increase in complications in
      patients continuing to take warfarin compared with controls. Patients with RRD
      are more likely to have vitreous haemorrhage at presentation if they are on
      warfarin.

PMID- 21071763
TI  - Pulmonary puzzle. An unusual cause of chest pain. Diagnosis: Cor triatriatum
      sinistrum with secondary unilateral pulmonary venous hypertension and right lung
      hypoplasia.

PMID- 21071764
TI  - Long-term follow-up high-resolution CT findings in non-specific interstitial
      pneumonia.
AB  - BACKGROUND: The aims of this study were to retrospectively assess the change in
      findings on follow-up CT scans of patients with non-specific interstitial
      pneumonia (NSIP; median, 72 months; range, 3-216 months) and to clarify the
      correlation between the baseline CT findings and mortality. METHODS: The study
      included 50 patients with a histologic diagnosis of NSIP. Two observers evaluated
      the high-resolution CT (HRCT) findings independently and classified each case
      into one of the following three categories: (1) compatible with NSIP, (2)
      compatible with UIP or (3) suggestive of alternative diagnosis. The correlation
      between the HRCT findings and mortality was evaluated using the Kaplan-Meier
      method and the log-rank test, as well as Cox proportional hazards regression
      models. RESULTS: Ground-glass opacity and consolidation decreased, whereas
      coarseness of fibrosis and traction bronchiectasis increased on the follow-up
      HRCT scans, however, in 78% of cases the overall extent of parenchymal
      abnormalities had no change or decreased. Patients with HRCT diagnosed compatible
      with NSIP had a longer survival than those with HRCT findings more compatible UIP
      or an alternative diagnosis. On multivariate analysis, the coarseness of fibrosis
      alone was associated with prognosis (HR: 1.480; 95% CIs 1.100 to 1.990).
      CONCLUSIONS: The HRCT patterns seen in patients with a histopathologic diagnosis
      of NSIP progress in a variable manner. Overall disease extent may decrease over
      time in some, while fibrosis may progress in others. The initial HRCT diagnosis
      may impact survival in this group of patients.

PMID- 21071765
TI  - Understanding the effect of compensation on recovery from severe motor vehicle
      crash injuries: a qualitative study.
AB  - OBJECTIVE: To explore the factors that influence recovery from serious injuries
      sustained in motor vehicle crashes, particularly differences between those with
      compensable and non-compensable injuries. DESIGN AND SETTING: Qualitative study
      using grounded theory and focus group methods within the trauma service of a
      university teaching hospital. PARTICIPANTS: 34 subjects (27 male, 7 female), of
      whom 21 were participants with a compensation claim and 13 were not. Each had
      sustained injuries in motor vehicle crashes between two and seven years
      previously. MAIN OUTCOME MEASURE: Themes identified from transcripts of the focus
      groups. RESULTS: The themes identified from participants claiming compensation
      were a strong sense of entitlement and injustice, a difficult claims and
      settlement process, an inability to move on with life during the claims process,
      an extreme dislike of medico-legal assessments, the necessity of legal
      representation to assist with the claims process, and a perceived lack of trust
      about having to prove an injury or disability. The themes common to all
      participants were the significance of the trauma experience, the importance of
      family and social support, and, if self-employed, financial hardship and
      difficult experiences in returning to work. CONCLUSIONS: The injury recovery
      experience was difficult for all subjects, but it was particularly stressful for
      those claiming compensation. Based on this study, the claims process,
      particularly medico-legal examinations, and other factors that could impact on
      injury recovery, are targets for further research, possible policy review, or
      legislative change.

PMID- 21071766
TI  - Hip protectors for preventing hip fractures in older people.

PMID- 21071767
TI  - Effectiveness of an external ankle brace in reducing parachuting-related ankle
      injuries.
AB  - Outside-the-boot parachute ankle braces (PABs) worn during US Army paratrooper
      training have been shown to reduce the risk of severe ankle injuries. In spite of
      evidence to the contrary, anecdotal reports continue to suggest increases in risk
      of other types of injury, and the cost of obtaining and periodically replacing
      the PAB has been used to justify its discontinued use. The authors identified
      inpatient and outpatient treatment for injuries during US Army paratrooper
      training. Those undergoing training during two periods when PAB use was mandated
      had 40% lower risks of ankle injury (brace I, RR=0.60 (95% CI 0.47 to 0.75);
      brace II, RR=0.62 (95% CI 0.49 to 0.78)), with no difference in risks of other
      types of injury. There were no differences in risk of ankle injury during periods
      when brace use was not mandated. The PAB is safe, effective and cost effective.

PMID- 21071768
TI  - Road safety in 10 countries.

PMID- 21071770
TI  - On the use of phloem sap delta13C as an indicator of canopy carbon
      discrimination.
AB  - In this study we measured delta13C in various carbon pools along the basipetal
      transport pathway in co-occurring Pinus pinaster and Acacia longifolia trees
      under Mediterranean climate conditions in the field. Overall, species differences
      in photosynthetic discrimination resulted in more enriched delta13C values in the
      water-conserving overstory P. pinaster relative to the water-spending understory
      invasive A. longifolia. Post-photosynthetic fractionation effects resulted in
      differences in delta13C of water-soluble organic matter pools along the plant
      axis with progressive depletion in delta13C from the canopy to the trunk
      (~6.50/00 depletion in A. longifolia and ~0.80/00 depletion in P. pinaster).
      Regardless of these fractionation effects, phloem sap delta13C in both terminal
      branches and the main stem correlated well with environmental parameters driving
      photosynthesis for both species, indicating that phloem sap delta13C has
      potential as an integrative tracer of changes in canopy carbon discrimination
      (Delta13C). Furthermore, we illustrate that a simple model based on sap flow
      estimated canopy stomatal conductance (G(S)) and phloem sap delta13C measurements
      has significant potential as a tool for estimating canopy-level carbon
      assimilation rates.

PMID- 21071769
TI  - Evidence that prestin has at least two voltage-dependent steps.
AB  - Prestin is a voltage-dependent membrane-spanning motor protein that confers
      electromotility on mammalian cochlear outer hair cells, which is essential for
      normal hearing of mammals. Voltage-induced charge movement in the prestin
      molecule is converted into mechanical work; however, little is known about the
      molecular mechanism of this process. For understanding the electromechanical
      coupling mechanism of prestin, we simultaneously measured voltage-dependent
      charge movement and electromotility under conditions in which the magnitudes of
      both charge movement and electromotility are gradually manipulated by the prestin
      inhibitor, salicylate. We show that the observed relationships of the charge
      movement and the physical displacement (q-d relations) are well represented by a
      three-state Boltzmann model but not by a two-state model or its previously
      proposed variant. Here, we suggest a molecular mechanism of prestin with at least
      two voltage-dependent conformational transition steps having distinct
      electromechanical coupling efficiencies.

PMID- 21071771
TI  - Different growth sensitivity to enhanced UV-B radiation between male and female
      Populus cathayana.
AB  - We investigated sex-related morphological and physiological responses to enhanced
      UV-B radiation in the dioecious species Populus cathayana Rehd. Cuttings were
      subjected to two UV-B radiation regimes: ambient (4.5 kJ m-2 day-1) and enhanced
      (12.5 kJ m-2 day-1) biologically effective UV-B radiation for one growing season.
      Enhanced UV-B radiation was found to significantly decrease the shoot height and
      basal diameter and to reduce the leaf area, dry matter accumulation, net
      photosynthesis rate (P(n)), chlorophyll a/b ratio (Chl a/b) and anthocyanin
      content. Enhanced UV-B radiation also increased chlorophyll pigment, leaf
      nitrogen, malondialdehyde and abscisic acid (ABA) content, superoxide dismutase
      and peroxidase activities and UV-B-absorbing compounds. No significant effects of
      enhanced UV-B radiation were found on biomass allocation, gas exchange (except
      for P(n)), photochemical efficiency of photosystem II or water use efficiency.
      Moreover, different sensitivity to enhanced UV-B radiation between males and
      females was detected. Under enhanced UV-B radiation, males exhibited
      significantly higher basal diameter and leaf nitrogen, and lower Chl a/b, ABA
      content, UV-B-absorbing compounds, as well as less decrement of leaf area and dry
      matter accumulation than did females. However, no significant sexual differences
      in these traits were found under ambient UV-B radiation. Our results suggest that
      males may possess a greater UV-B resistance than do females, with males having a
      more efficient antioxidant system and higher anthocyanin content to alleviate UV
      B penetration stress than females.

PMID- 21071772
TI  - Vascular prevention and dementia.

PMID- 21071773
TI  - Vascular risk factors and dementia--towards prevention strategies.
AB  - Several cohort studies have shown that vascular risk factors including
      hypertension, hypercholesterolaemia, diabetes mellitus, smoking, obesity and lack
      of physical exercise in midlife and to a lesser extent in late life, are
      associated with an increased risk of dementia. The results from randomised
      controlled clinical trials on treatment of these risk factors are not conclusive
      for the effect on cognitive decline and dementia. Studies investigating the
      effect of a multi-component intervention aimed at vascular risk factors to
      prevent or slow down cognitive decline and dementia will hopefully give the
      answer as to whether such an intervention is efficacious. This requires large
      clinical trials in an elderly population with long follow-up and several
      competing risks, making it difficult from an organisational and methodological
      point of view. Major challenges for future studies are to select the optimal
      population, set the optimal treatment targets and select clinically relevant
      outcome parameters.

PMID- 21071774
TI  - Gene expression profiles of the oestrogen receptor in breast cancer.
AB  - Breast cancer is a heterogeneous disease and existing clinicopathological
      classifications do not fully capture the diversity in clinical disease course.
      Since the oestrogen receptor (ER) plays a central role in the crosstalk between
      different signalling pathways in breast cancer, the expression of this receptor
      is important for the behaviour of breast cancer cells and is reflected in gene
      expression patterns of breast tumours. High throughput analysis of gene
      expression of breast cancer has increased the insights into ER signalling,
      including its relation with disease outcome and therapy response. Expression of
      ER and its numerous downstream targets are driving patterns of gene expression
      and dominate unsupervised analyses in the breast cancer specimens studied to
      date, regardless of microarray platform or statistical approach. This paper
      reviews gene expression studies either attempting to unravel the functional
      effect of ER or describing the gene expression profiles driven by ER in breast
      tumours. In addition, the development of molecular signatures predicting response
      to endocrine treatment will be discussed.

PMID- 21071775
TI  - Pathophysiology and prevention of diverticulitis and perforation.
AB  - OBJECTIVE: This article gives an overview of the current evidence and theories in
      the pathophysiology of diverticulosis, diverticulitis and perforation and
      discusses its prevention. BACKGROUND: Diverticular disease is one of the most
      common diseases related to the gastrointestinal tract in Western countries. The
      pathogenesis of this disease process is probably multifactorial, but remains
      poorly understood and inadequately investigated. METHODS: A literature search was
      performed in order to give an overview of the current evidence and theories in
      the pathophysiology of diverticula formation and the factors related to
      progression towards inflammation and even perforation. Strategies for prevention
      of (perforated) diverticulitis are also discussed. RESULTS/CONCLUSION: The
      pathogenesis of diverticular disease and its complications seems to be a result
      of a complex interaction between exposure to a low-fibre diet, possible genetic
      influences, the coexistence of other bowel diseases and the impact of medicine
      use. This eventually leads to alterations in colonic pressures and motility and
      structural changes of the colon wall. Unfortunately the evidence is frequently
      conflicting in the present literature or lacking altogether.

PMID- 21071776
TI  - Chronic yersiniosis due to defects in the TLR5 and NOD2 recognition pathways.
AB  - Infection with Yersinia enterocolitica leads to a self-limiting disease, but in a
      small number of cases a protracted course can develop. The host genetic factors
      contributing to the advancement of the disease to the chronic phase are not
      known. We describe a patient suffering from an abdominal inflammatory mass due to
      chronic yersiniosis. Functional assays revealed defects in the recognition of
      flagellin by Toll-like receptor 5 (TLR5) and of muramyl dipeptide by NOD2,
      leading to a defective inflammatory response to Yersinia enterocolitica. Genetic
      sequencing showed that the patient was compound heterozygous for five different
      mutations in TLR5, while being homozygous for the 3020insC NOD2 mutation. In
      conclusion, we describe a patient in whom specific defects in the TLR5 and NOD2
      recognition pathways led to chronic yersiniosis.

PMID- 21071777
TI  - Central nervous system involvement in a rare genetic iron overload disorder.
AB  - In most genetic iron overload disorders the diagnosis can be rejected when
      transferrin saturation is low. We describe a patient and her family with
      hyperferritinaemia and low transferrin saturation with iron accumulation in the
      central nervous system (CNS) and liver due to hereditary aceruloplasminaemia. In
      this rare genetic iron overload disorder oxidation of iron is disturbed,
      resulting in storage of iron in the CNS and visceral organs.

PMID- 21071778
TI  - An abdominal mass: not a 'clear cut' case! Actinomycosis.

PMID- 21071779
TI  - Shoulder pain in two HIV-seropositive patients. Avascular necrosis (AVN) of the
      bone.

PMID- 21071780
TI  - An unusual urinary tract infection! Myiasis.

PMID- 21071781
TI  - Large nocturnal eyes causing gastrointestinal bleeding in asymptomatic multiple
      myeloma. CMV enterocolitis.

PMID- 21071782
TI  - Semi-final masked hypertension.
AB  - Masked hypertension is normal blood pressures (BP) in a clinical setting and high
      BP during ambulatory monitoring. Although these patients are at higher
      cardiovascular risk, there is still no clear consensus definition of masked
      hypertension.

PMID- 21071783
TI  - Intermittent use of pantoprazole and famotidine in severe hypomagnesaemia due to
      omeprazole.

PMID- 21071784
TI  - An immersive virtual peer for studying social influences on child cyclists' road
      crossing behavior.
AB  - The goal of our work is to develop a programmatically controlled peer to bicycle
      with a human subject for the purpose of studying how social interactions
      influence road-crossing behavior. The peer is controlled through a combination of
      reactive controllers that determine the gross motion of the virtual bicycle,
      action-based controllers that animate the virtual bicyclist and generate verbal
      behaviors, and a keyboard interface that allows an experimenter to initiate the
      virtual bicyclist's actions during the course of an experiment. The virtual
      bicyclist's repertoire of behaviors includes road following, riding alongside the
      human rider, stopping at intersections, and crossing intersections through
      specified gaps in traffic. The virtual cyclist engages the human subject through
      gaze, gesture, and verbal interactions. We describe the structure of the behavior
      code and report the results of a study examining how 10- and 12-year-old children
      interact with a peer cyclist that makes either risky or safe choices in selecting
      gaps in traffic. Results of our study revealed that children who rode with a
      risky peer were more likely to cross intermediate-sized gaps than children who
      rode with a safe peer. In addition, children were significantly less likely to
      stop at the last six intersections after the experience of riding with the risky
      than the safe peer during the first six intersections. The results of the study
      and children's reactions to the virtual peer indicate that our virtual peer
      framework is a promising platform for future behavioral studies of peer
      influences on children's bicycle riding behavior.

PMID- 21071785
TI  - Virtualized Traffic: reconstructing traffic flows from discrete spatiotemporal
      data.
AB  - We present a novel concept, Virtualized Traffic, to reconstruct and visualize
      continuous traffic flows from discrete spatiotemporal data provided by traffic
      sensors or generated artificially to enhance a sense of immersion in a dynamic
      virtual world. Given the positions of each car at two recorded locations on a
      highway and the corresponding time instances, our approach can reconstruct the
      traffic flows (i.e., the dynamic motions of multiple cars over time) between the
      two locations along the highway for immersive visualization of virtual cities or
      other environments. Our algorithm is applicable to high-density traffic on
      highways with an arbitrary number of lanes and takes into account the geometric,
      kinematic, and dynamic constraints on the cars. Our method reconstructs the car
      motion that automatically minimizes the number of lane changes, respects safety
      distance to other cars, and computes the acceleration necessary to obtain a
      smooth traffic flow subject to the given constraints. Furthermore, our framework
      can process a continuous stream of input data in real time, enabling the users to
      view virtualized traffic events in a virtual world as they occur. We demonstrate
      our reconstruction technique with both synthetic and real-world input.

PMID- 21071786
TI  - A spatially augmented reality sketching interface for architectural daylighting
      design.
AB  - We present an application of interactive global illumination and spatially
      augmented reality to architectural daylight modeling that allows designers to
      explore alternative designs and new technologies for improving the sustainability
      of their buildings. Images of a model in the real world, captured by a camera
      above the scene, are processed to construct a virtual 3D model. To achieve
      interactive rendering rates, we use a hybrid rendering technique, leveraging
      radiosity to simulate the interreflectance between diffuse patches and shadow
      volumes to generate per-pixel direct illumination. The rendered images are then
      projected on the real model by four calibrated projectors to help users study the
      daylighting illumination. The virtual heliodon is a physical design environment
      in which multiple designers, a designer and a client, or a teacher and students
      can gather to experience animated visualizations of the natural illumination
      within a proposed design by controlling the time of day, season, and climate.
      Furthermore, participants may interactively redesign the geometry and materials
      of the space by manipulating physical design elements and see the updated
      lighting simulation.

PMID- 21071787
TI  - Unicube for dynamic environment mapping.
AB  - Cube mapping is widely used in many graphics applications due to the availability
      of hardware support. However, it does not sample the spherical surface evenly.
      Recently, a uniform spherical mapping, isocube mapping, was proposed. It exploits
      the six-face structure used in cube mapping and samples the spherical surface
      evenly. Unfortunately, some texels in isocube mapping are not rectilinear. This
      nonrectilinear property may degrade the filtering quality. This paper proposes a
      novel spherical mapping, namely unicube mapping. It has the advantages of cube
      mapping (exploitation of hardware and rectilinear structure) and isocube mapping
      (evenly sampling pattern). In the implementation, unicube mapping uses a simple
      function to modify the lookup vector before the conventional cube map lookup
      process. Hence, unicube mapping fully exploits the cube map hardware for real
      time filtering and lookup. More importantly, its rectilinear partition structure
      allows a direct and real-time acquisition of the texture environment. This
      property facilitates dynamic environment mapping in a real time manner.

PMID- 21071788
TI  - Video painting with space-time-varying style parameters.
AB  - Artists use different means of stylization to control the focus on different
      objects in the scene. This allows them to portray complex meaning and achieve
      certain artistic effects. Most prior work on painterly rendering of videos,
      however, uses only a single painting style, with fixed global parameters,
      irrespective of objects and their layout in the images. This often leads to
      inadequate artistic control. Moreover, brush stroke orientation is typically
      assumed to follow an everywhere continuous directional field. In this paper, we
      propose a video painting system that accounts for the spatial support of objects
      in the images or videos, and uses this information to specify style parameters
      and stroke orientation for painterly rendering. Since objects occupy distinct
      image locations and move relatively smoothly from one video frame to another, our
      object-based painterly rendering approach is characterized by style parameters
      that coherently vary in space and time. Space-time-varying style parameters
      enable more artistic freedom, such as emphasis/de-emphasis, increase or decrease
      of contrast, exaggeration or abstraction of different objects in the scene in a
      temporally coherent fashion.

PMID- 21071789
TI  - Inductively generating Euler diagrams.
AB  - Euler diagrams have a wide variety of uses, from information visualization to
      logical reasoning. In all of their application areas, the ability to
      automatically layout Euler diagrams brings considerable benefits. In this paper,
      we present a novel approach to Euler diagram generation. We develop certain
      graphs associated with Euler diagrams in order to allow curves to be added by
      finding cycles in these graphs. This permits us to build Euler diagrams
      inductively, adding one curve at a time. Our technique is adaptable, allowing the
      easy specification, and enforcement, of sets of well-formedness conditions; we
      present a series of results that identify properties of cycles that correspond to
      the well-formedness conditions. This improves upon other contributions toward the
      automated generation of Euler diagrams which implicitly assume some fixed set of
      well-formedness conditions must hold. In addition, unlike most of these other
      generation methods, our technique allows any abstract description to be drawn as
      an Euler diagram. To establish the utility of the approach, a prototype
      implementation has been developed.

PMID- 21071790
TI  - Automatic metro map layout using multicriteria optimization.
AB  - This paper describes an automatic mechanism for drawing metro maps. We apply
      multicriteria optimization to find effective placement of stations with a good
      line layout and to label the map unambiguously. A number of metrics are defined,
      which are used in a weighted sum to find a fitness value for a layout of the map.
      A hill climbing optimizer is used to reduce the fitness value, and find improved
      map layouts. To avoid local minima, we apply clustering techniques to the map-the
      hill climber moves both stations and clusters when finding improved layouts. We
      show the method applied to a number of metro maps, and describe an empirical
      study that provides some quantitative evidence that automatically-drawn metro
      maps can help users to find routes more efficiently than either published maps or
      undistorted maps. Moreover, we have found that, in these cases, study subjects
      indicate a preference for automatically-drawn maps over the alternatives.

PMID- 21071791
TI  - Shape "break-and-repair" strategy and its application to automated medical image
      segmentation.
AB  - In three-dimensional medical imaging, segmentation of specific anatomy structure
      is often a preprocessing step for computer-aided detection/diagnosis (CAD)
      purposes, and its performance has a significant impact on diagnosis of diseases
      as well as objective quantitative assessment of therapeutic efficacy. However,
      the existence of various diseases, image noise or artifacts, and individual
      anatomical variety generally impose a challenge for accurate segmentation of
      specific structures. To address these problems, a shape analysis strategy termed
      "break-and-repair" is presented in this study to facilitate automated medical
      image segmentation. Similar to surface approximation using a limited number of
      control points, the basic idea is to remove problematic regions and then estimate
      a smooth and complete surface shape by representing the remaining regions with
      high fidelity as an implicit function. The innovation of this shape analysis
      strategy is the capability of solving challenging medical image segmentation
      problems in a unified framework, regardless of the variability of anatomical
      structures in question. In our implementation, principal curvature analysis is
      used to identify and remove the problematic regions and radial basis function
      (RBF) based implicit surface fitting is used to achieve a closed (or complete)
      surface boundary. The feasibility and performance of this strategy are
      demonstrated by applying it to automated segmentation of two completely different
      anatomical structures depicted on CT examinations, namely human lungs and
      pulmonary nodules. Our quantitative experiments on a large number of clinical CT
      examinations collected from different sources demonstrate the accuracy,
      robustness, and generality of the shape "break-and-repair" strategy in medical
      image segmentation.

PMID- 21071792
TI  - A fast algorithm for computing geodesic distances in tree space.
AB  - Comparing and computing distances between phylogenetic trees are important
      biological problems, especially for models where edge lengths play an important
      role. The geodesic distance measure between two phylogenetic trees with edge
      lengths is the length of the shortest path between them in the continuous tree
      space introduced by Billera, Holmes, and Vogtmann. This tree space provides a
      powerful tool for studying and comparing phylogenetic trees, both in exhibiting a
      natural distance measure and in providing a euclidean-like structure for solving
      optimization problems on trees. An important open problem is to find a polynomial
      time algorithm for finding geodesics in tree space. This paper gives such an
      algorithm, which starts with a simple initial path and moves through a series of
      successively shorter paths until the geodesic is attained.

PMID- 21071793
TI  - A general framework for analyzing data from two short time-series microarray
      experiments.
AB  - We propose a general theoretical framework for analyzing differentially expressed
      genes and behavior patterns from two homogenous short time-course data. The
      framework generalizes the recently proposed Hilbert-Schmidt Independence
      Criterion (HSIC)-based framework adapting it to the time-series scenario by
      utilizing tensor analysis for data transformation. The proposed framework is
      effective in yielding criteria that can identify both the differentially
      expressed genes and time-course patterns of interest between two time-series
      experiments without requiring to explicitly cluster the data. The results,
      obtained by applying the proposed framework with a linear kernel formulation, on
      various data sets are found to be both biologically meaningful and consistent
      with published studies.

PMID- 21071794
TI  - Efficient formulations for exact stochastic simulation of chemical systems.
AB  - One can generate trajectories to simulate a system of chemical reactions using
      either Gillespie's direct method or Gibson and Bruck's next reaction method.
      Because one usually needs many trajectories to understand the dynamics of a
      system, performance is important. In this paper, we present new formulations of
      these methods that improve the computational complexity of the algorithms. We
      present optimized implementations, available from http://cain.sourceforge.net/,
      that offer better performance than previous work. There is no single method that
      is best for all problems. Simple formulations often work best for systems with a
      small number of reactions, while some sophisticated methods offer the best
      performance for large problems and scale well asymptotically. We investigate the
      performance of each formulation on simple biological systems using a wide range
      of problem sizes. We also consider the numerical accuracy of the direct and the
      next reaction method. We have found that special precautions must be taken in
      order to ensure that randomness is not discarded during the course of a
      simulation.

PMID- 21071795
TI  - Estimating haplotype frequencies by combining data from large DNA pools with
      database information.
AB  - We assume that allele frequency data have been extracted from several large DNA
      pools, each containing genetic material of up to hundreds of sampled individuals.
      Our goal is to estimate the haplotype frequencies among the sampled individuals
      by combining the pooled allele frequency data with prior knowledge about the set
      of possible haplotypes. Such prior information can be obtained, for example, from
      a database such as HapMap. We present a Bayesian haplotyping method for pooled
      DNA based on a continuous approximation of the multinomial distribution. The
      proposed method is applicable when the sizes of the DNA pools and/or the number
      of considered loci exceed the limits of several earlier methods. In the example
      analyses, the proposed model clearly outperforms a deterministic greedy algorithm
      on real data from the HapMap database. With a small number of loci, the
      performance of the proposed method is similar to that of an EM-algorithm, which
      uses a multinormal approximation for the pooled allele frequencies, but which
      does not utilize prior information about the haplotypes. The method has been
      implemented using Matlab and the code is available upon request from the authors.

PMID- 21071797
TI  - Fast surface-based travel depth estimation algorithm for macromolecule surface
      shape description.
AB  - Travel Depth, introduced by Coleman and Sharp in 2006, is a physical
      interpretation of molecular depth, a term frequently used to describe the shape
      of a molecular active site or binding site. Travel Depth can be seen as the
      physical distance a solvent molecule would have to travel from a point of the
      surface, i.e., the Solvent-Excluded Surface (SES), to its convex hull. Existing
      algorithms providing an estimation of the Travel Depth are based on a regular
      sampling of the molecule volume and the use of the Dijkstra's shortest path
      algorithm. Since Travel Depth is only defined on the molecular surface, this
      volume-based approach is characterized by a large computational complexity due to
      the processing of unnecessary samples lying inside or outside the molecule. In
      this paper, we propose a surface-based approach that restricts the processing to
      data defined on the SES. This algorithm significantly reduces the complexity of
      Travel Depth estimation and makes possible the analysis of large macromolecule
      surface shape description with high resolution. Experimental results show that
      compared to existing methods, the proposed algorithm achieves accurate
      estimations with considerably reduced processing times.

PMID- 21071796
TI  - F2Dock: fast Fourier protein-protein docking.
AB  - The functions of proteins are often realized through their mutual interactions.
      Determining a relative transformation for a pair of proteins and their
      conformations which form a stable complex, reproducible in nature, is known as
      docking. It is an important step in drug design, structure determination, and
      understanding function and structure relationships. In this paper, we extend our
      nonuniform fast Fourier transform-based docking algorithm to include an adaptive
      search phase (both translational and rotational) and thereby speed up its
      execution. We have also implemented a multithreaded version of the adaptive
      docking algorithm for even faster execution on multicore machines. We call this
      protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated
      F2Dock based on an extensive experimental study on a list of benchmark complexes
      and conclude that F2Dock works very well in practice. Though all docking results
      reported in this paper use shape complementarity and Coulombic-potential-based
      scores only, F2Dock is structured to incorporate Lennard-Jones potential and
      reranking docking solutions based on desolvation energy .

PMID- 21071798
TI  - Finding significant matches of position weight matrices in linear time.
AB  - Position weight matrices are an important method for modeling signals or motifs
      in biological sequences, both in DNA and protein contexts. In this paper, we
      present fast algorithms for the problem of finding significant matches of such
      matrices. Our algorithms are of the online type, and they generalize classical
      multipattern matching, filtering, and superalphabet techniques of combinatorial
      string matching to the problem of weight matrix matching. Several variants of the
      algorithms are developed, including multiple matrix extensions that perform the
      search for several matrices in one scan through the sequence database.
      Experimental performance evaluation is provided to compare the new techniques
      against each other as well as against some other online and index-based
      algorithms proposed in the literature. Compared to the brute-force O(mn)
      approach, our solutions can be faster by a factor that is proportional to the
      matrix length m. Our multiple-matrix filtration algorithm had the best
      performance in the experiments. On a current PC, this algorithm finds significant
      matches (p = 0.0001) of the 123 JASPAR matrices in the human genome in about 18
      minutes.

PMID- 21071799
TI  - Fuzzy ARTMAP prediction of biological activities for potential HIV-1 protease
      inhibitors using a small molecular data set.
AB  - Obtaining satisfactory results with neural networks depends on the availability
      of large data samples. The use of small training sets generally reduces
      performance. Most classical Quantitative Structure-Activity Relationship (QSAR)
      studies for a specific enzyme system have been performed on small data sets. We
      focus on the neuro-fuzzy prediction of biological activities of HIV-1 protease
      inhibitory compounds when inferring from small training sets. We propose two
      computational intelligence prediction techniques which are suitable for small
      training sets, at the expense of some computational overhead. Both techniques are
      based on the FAMR model. The FAMR is a Fuzzy ARTMAP (FAM) incremental learning
      system used for classification and probability estimation. During the learning
      phase, each sample pair is assigned a relevance factor proportional to the
      importance of that pair. The two proposed algorithms in this paper are: 1) The GA
      FAMR algorithm, which is new, consists of two stages: a) During the first stage,
      we use a genetic algorithm (GA) to optimize the relevances assigned to the
      training data. This improves the generalization capability of the FAMR. b) In the
      second stage, we use the optimized relevances to train the FAMR. 2) The Ordered
      FAMR is derived from a known algorithm. Instead of optimizing relevances, it
      optimizes the order of data presentation using the algorithm of Dagher et al. In
      our experiments, we compare these two algorithms with an algorithm not based on
      the FAM, the FS-GA-FNN introduced in [4], [5]. We conclude that when inferring
      from small training sets, both techniques are efficient, in terms of
      generalization capability and execution time. The computational overhead
      introduced is compensated by better accuracy. Finally, the proposed techniques
      are used to predict the biological activities of newly designed potential HIV-1
      protease inhibitors.

PMID- 21071800
TI  - Genetic networks and soft computing.
AB  - The analysis of gene regulatory networks provides enormous information on various
      fundamental cellular processes involving growth, development, hormone secretion,
      and cellular communication. Their extraction from available gene expression
      profiles is a challenging problem. Such reverse engineering of genetic networks
      offers insight into cellular activity toward prediction of adverse effects of new
      drugs or possible identification of new drug targets. Tasks such as
      classification, clustering, and feature selection enable efficient mining of
      knowledge about gene interactions in the form of networks. It is known that
      biological data is prone to different kinds of noise and ambiguity. Soft
      computing tools, such as fuzzy sets, evolutionary strategies, and neurocomputing,
      have been found to be helpful in providing low-cost, acceptable solutions in the
      presence of various types of uncertainties. In this paper, we survey the role of
      these soft methodologies and their hybridizations, for the purpose of generating
      genetic networks.

PMID- 21071801
TI  - Identification and modeling of genes with diurnal oscillations from microarray
      time series data.
AB  - Behavior of living organisms is strongly modulated by the day and night cycle
      giving rise to a cyclic pattern of activities. Such a pattern helps the organisms
      to coordinate their activities and maintain a balance between what could be
      performed during the "day" and what could be relegated to the "night." This
      cyclic pattern, called the "Circadian Rhythm," is a biological phenomenon
      observed in a large number of organisms. In this paper, our goal is to analyze
      transcriptome data from Cyanothece for the purpose of discovering genes whose
      expressions are rhythmic. We cluster these genes into groups that are close in
      terms of their phases and show that genes from a specific metabolic functional
      category are tightly clustered, indicating perhaps a "preferred time of the
      day/night" when the organism performs this function. The proposed analysis is
      applied to two sets of microarray experiments performed under varying incident
      light patterns. Subsequently, we propose a model with a network of three phase
      oscillators together with a central master clock and use it to approximate a set
      of "circadian-controlled genes" that can be approximated closely.

PMID- 21071802
TI  - Influence of prior knowledge in constraint-based learning of gene regulatory
      networks.
AB  - Constraint-based structure learning algorithms generally perform well on sparse
      graphs. Although sparsity is not uncommon, there are some domains where the
      underlying graph can have some dense regions; one of these domains is gene
      regulatory networks, which is the main motivation to undertake the study
      described in this paper. We propose a new constraint-based algorithm that can
      both increase the quality of output and decrease the computational requirements
      for learning the structure of gene regulatory networks. The algorithm is based on
      and extends the PC algorithm. Two different types of information are derived from
      the prior knowledge; one is the probability of existence of edges, and the other
      is the nodes that seem to be dependent on a large number of nodes compared to
      other nodes in the graph. Also a new method based on Gene Ontology for gene
      regulatory network validation is proposed. We demonstrate the applicability and
      effectiveness of the proposed algorithms on both synthetic and real data sets.

PMID- 21071803
TI  - Information-theoretic model of evolution over protein communication channel.
AB  - In this paper, we propose a communication model of evolution and investigate its
      information-theoretic bounds. The process of evolution is modeled as the
      retransmission of information over a protein communication channel, where the
      transmitted message is the organism's proteome encoded in the DNA. We compute the
      capacity and the rate distortion functions of the protein communication system
      for the three domains of life: Archaea, Bacteria, and Eukaryotes. The tradeoff
      between the transmission rate and the distortion in noisy protein communication
      channels is analyzed. As expected, comparison between the optimal transmission
      rate and the channel capacity indicates that the biological fidelity does not
      reach the Shannon optimal distortion. However, the relationship between the
      channel capacity and rate distortion achieved for different biological domains
      provides tremendous insight into the dynamics of the evolutionary processes of
      the three domains of life. We rely on these results to provide a model of genome
      sequence evolution based on the two major evolutionary driving forces: mutations
      and unequal crossovers.

PMID- 21071804
TI  - Learning genetic regulatory network connectivity from time series data.
AB  - Recent experimental advances facilitate the collection of time series data that
      indicate which genes in a cell are expressed. This information can be used to
      understand the genetic regulatory network that generates the data. Typically,
      Bayesian analysis approaches are applied which neglect the time series nature of
      the experimental data, have difficulty in determining the direction of causality,
      and do not perform well on networks with tight feedback. To address these
      problems, this paper presents a method to learn genetic network connectivity
      which exploits the time series nature of experimental data to achieve better
      causal predictions. This method first breaks up the data into bins. Next, it
      determines an initial set of potential influence vectors for each gene based upon
      the probability of the gene's expression increasing in the next time step. These
      vectors are then combined to form new vectors with better scores. Finally, these
      influence vectors are competed against each other to determine the final
      influence vector for each gene. The result is a directed graph representation of
      the genetic network's repression and activation connections. Results are reported
      for several synthetic networks with tight feedback showing significant
      improvements in recall and runtime over Yu's dynamic Bayesian approach. Promising
      preliminary results are also reported for an analysis of experimental data for
      genes involved in the yeast cell cycle.

PMID- 21071805
TI  - Model reduction using piecewise-linear approximations preserves dynamic
      properties of the carbon starvation response in Escherichia coli.
AB  - The adaptation of the bacterium Escherichia coli to carbon starvation is
      controlled by a large network of biochemical reactions involving genes, mRNAs,
      proteins, and signalling molecules. The dynamics of these networks is difficult
      to analyze, notably due to a lack of quantitative information on parameter
      values. To overcome these limitations, model reduction approaches based on quasi
      steady-state (QSS) and piecewise-linear (PL) approximations have been proposed,
      resulting in models that are easier to handle mathematically and computationally.
      These approximations are not supposed to affect the capability of the model to
      account for essential dynamical properties of the system, but the validity of
      this assumption has not been systematically tested. In this paper, we carry out
      such a study by evaluating a large and complex PL model of the carbon starvation
      response in E. coli using an ensemble approach. The results show that, in
      comparison with conventional nonlinear models, the PL approximations generally
      preserve the dynamics of the carbon starvation response network, although with
      some deviations concerning notably the quantitative precision of the model
      predictions. This encourages the application of PL models to the qualitative
      analysis of bacterial regulatory networks, in situations where the reference time
      scale is that of protein synthesis and degradation.

PMID- 21071806
TI  - New methods for inference of local tree topologies with recombinant SNP sequences
      in populations.
AB  - Large amount of population-scale genetic variation data are being collected in
      populations. One potentially important biological problem is to infer the
      population genealogical history from these genetic variation data. Partly due to
      recombination, genealogical history of a set of DNA sequences in a population
      usually cannot be represented by a single tree. Instead, genealogy is better
      represented by a genealogical network, which is a compact representation of a set
      of correlated local genealogical trees, each for a short region of genome and
      possibly with different topology. Inference of genealogical history for a set of
      DNA sequences under recombination has many potential applications, including
      association mapping of complex diseases. In this paper, we present two new
      methods for reconstructing local tree topologies with the presence of
      recombination, which extend and improve the previous work in. We first show that
      the "tree scan" method can be converted to a probabilistic inference method based
      on a hidden Markov model. We then focus on developing a novel local tree
      inference method called RENT that is both accurate and scalable to larger data.
      Through simulation, we demonstrate the usefulness of our methods by showing that
      the hidden-Markov-model-based method is comparable with the original method in
      terms of accuracy. We also show that RENT is competitive with other methods in
      terms of inference accuracy, and its inference error rate is often lower and can
      handle large data.

PMID- 21071807
TI  - Pairwise statistical significance of local sequence alignment using sequence
      specific and position-specific substitution matrices.
AB  - Pairwise sequence alignment is a central problem in bioinformatics, which forms
      the basis of various other applications. Two related sequences are expected to
      have a high alignment score, but relatedness is usually judged by statistical
      significance rather than by alignment score. Recently, it was shown that pairwise
      statistical significance gives promising results as an alternative to database
      statistical significance for getting individual significance estimates of
      pairwise alignment scores. The improvement was mainly attributed to making the
      statistical significance estimation process more sequence-specific and database
      independent. In this paper, we use sequence-specific and position-specific
      substitution matrices to derive the estimates of pairwise statistical
      significance, which is expected to use more sequence-specific information in
      estimating pairwise statistical significance. Experiments on a benchmark database
      with sequence-specific substitution matrices at different levels of sequence
      specific contribution were conducted, and results confirm that using sequence
      specific substitution matrices for estimating pairwise statistical significance
      is significantly better than using a standard matrix like BLOSUM62, and than
      database statistical significance estimates reported by popular database search
      programs like BLAST, PSI-BLAST (without pretrained PSSMs), and SSEARCH on a
      benchmark database, but with pretrained PSSMs, PSI-BLAST results are
      significantly better. Further, using position-specific substitution matrices for
      estimating pairwise statistical significance gives significantly better results
      even than PSI-BLAST using pretrained PSSMs.

PMID- 21071808
TI  - Predicting metabolic fluxes using gene expression differences as constraints.
AB  - A standard approach to estimate intracellular fluxes on a genome-wide scale is
      flux-balance analysis (FBA), which optimizes an objective function subject to
      constraints on (relations between) fluxes. The performance of FBA models heavily
      depends on the relevance of the formulated objective function and the
      completeness of the defined constraints. Previous studies indicated that FBA
      predictions can be improved by adding regulatory on/off constraints. These
      constraints were imposed based on either absolute or relative gene expression
      values. We provide a new algorithm that directly uses regulatory up/down
      constraints based on gene expression data in FBA optimization (tFBA). Our
      assumption is that if the activity of a gene drastically changes from one
      condition to the other, the flux through the reaction controlled by that gene
      will change accordingly. We allow these constraints to be violated, to account
      for posttranscriptional control and noise in the data. These up/down constraints
      are less stringent than the on/off constraints as previously proposed.
      Nevertheless, we obtain promising predictions, since many up/down constraints can
      be enforced. The potential of the proposed method, tFBA, is demonstrated through
      the analysis of fluxes in yeast under nine different cultivation conditions,
      between which approximately 5,000 regulatory up/down constraints can be defined.
      We show that changes in gene expression are predictive for changes in fluxes.
      Additionally, we illustrate that flux distributions obtained with tFBA better fit
      transcriptomics data than previous methods. Finally, we compare tFBA and FBA
      predictions to show that our approach yields more biologically relevant results.

PMID- 21071809
TI  - Probabilistic analysis of probe reliability in differential gene expression
      studies with short oligonucleotide arrays.
AB  - Probe defects are a major source of noise in gene expression studies. While
      existing approaches detect noisy probes based on external information such as
      genomic alignments, we introduce and validate a targeted probabilistic method for
      analyzing probe reliability directly from expression data and independently of
      the noise source. This provides insights into the various sources of probe-level
      noise and gives tools to guide probe design.

PMID- 21071810
TI  - Topology improves phylogenetic motif functional site predictions.
AB  - Prediction of protein functional sites from sequence-derived data remains an open
      bioinformatics problem. We have developed a phylogenetic motif (PM) functional
      site prediction approach that identifies functional sites from alignment
      fragments that parallel the evolutionary patterns of the family. In our approach,
      PMs are identified by comparing tree topologies of each alignment fragment to
      that of the complete phylogeny. Herein, we bypass the phylogenetic reconstruction
      step and identify PMs directly from distance matrix comparisons. In order to
      optimize the new algorithm, we consider three different distance matrices and 13
      different matrix similarity scores. We assess the performance of the various
      approaches on a structurally nonredundant data set that includes three types of
      functional site definitions. Without exception, the predictive power of the
      original approach outperforms the distance matrix variants. While the distance
      matrix methods fail to improve upon the original approach, our results are
      important because they clearly demonstrate that the improved predictive power is
      based on the topological comparisons. Meaning that phylogenetic trees are a
      straightforward, yet powerful way to improve functional site prediction accuracy.
      While complementary studies have shown that topology improves predictions of
      protein-protein interactions, this report represents the first demonstration that
      trees improve functional site predictions as well.

PMID- 21071811
TI  - Twin removal in genetic algorithms for protein structure prediction using low
      resolution model.
AB  - This paper presents the impact of twins and the measures for their removal from
      the population of genetic algorithm (GA) when applied to effective conformational
      searching. It is conclusively shown that a twin removal strategy for a GA
      provides considerably enhanced performance when investigating solutions to
      complex ab initio protein structure prediction (PSP) problems in low-resolution
      model. Without twin removal, GA crossover and mutation operations can become
      ineffectual as generations lose their ability to produce significant differences,
      which can lead to the solution stalling. The paper relaxes the definition of
      chromosomal twins in the removal strategy to not only encompass identical, but
      also highly correlated chromosomes within the GA population, with empirical
      results consistently exhibiting significant improvements solving PSP problems.

PMID- 21071812
TI  - A weighted principal component analysis and its application to gene expression
      data.
AB  - In this work, we introduce in the first part new developments in Principal
      Component Analysis (PCA) and in the second part a new method to select variables
      (genes in our application). Our focus is on problems where the values taken by
      each variable do not all have the same importance and where the data may be
      contaminated with noise and contain outliers, as is the case with microarray
      data. The usual PCA is not appropriate to deal with this kind of problems. In
      this context, we propose the use of a new correlation coefficient as an
      alternative to Pearson's. This leads to a so-called weighted PCA (WPCA). In order
      to illustrate the features of our WPCA and compare it with the usual PCA, we
      consider the problem of analyzing gene expression data sets. In the second part
      of this work, we propose a new PCA-based algorithm to iteratively select the most
      important genes in a microarray data set. We show that this algorithm produces
      better results when our WPCA is used instead of the usual PCA. Furthermore, by
      using Support Vector Machines, we show that it can compete with the Significance
      Analysis of Microarrays algorithm.

PMID- 21071813
TI  - Disturbance analysis of nonlinear differential equation models of genetic SUM
      regulatory networks.
AB  - Noise disturbances and time delays are frequently met in cellular genetic
      regulatory systems. This paper is concerned with the disturbance analysis of a
      class of genetic regulatory networks described by nonlinear differential equation
      models. The mechanisms of genetic regulatory networks to amplify (attenuate)
      external disturbance are explored, and a simple measure of the amplification
      (attenuation) level is developed from a nonlinear robust control point of view.
      It should be noted that the conditions used to measure the disturbance level are
      delay-independent or delay-dependent, and are expressed within the framework of
      linear matrix inequalities, which can be characterized as convex optimization,
      and computed by the interior-point algorithm easily. Finally, by the proposed
      method, a numerical example is provided to illustrate how to measure the
      attenuation of proteins in the presence of external disturbances.

PMID- 21071814
TI  - Linear-time algorithms for the multiple gene duplication problems.
AB  - A fundamental problem arising in the evolutionary molecular biology is to
      discover the locations of gene duplications and multiple gene duplication
      episodes based on the phylogenetic information. The solutions to the MULTIPLE
      GENE DUPLICATION problems can provide useful clues to place the gene duplication
      events onto the locations of a species tree and to expose the multiple gene
      duplication episodes. In this paper, we study two variations of the MULTIPLE GENE
      DUPLICATION problems: the EPISODE-CLUSTERING (EC) problem and the MINIMUM
      EPISODES (ME) problem. For the EC problem, we improve the results of Burleigh et
      al. with an optimal linear-time algorithm. For the ME problem, on the basis of
      the algorithm presented by Bansal and Eulenstein, we propose an optimal linear
      time algorithm.

PMID- 21071815
TI  - Semi-Markov models for brownian dynamics permeation in biological ion channels.
AB  - Constructing accurate computational models that explain how ions permeate through
      a biological ion channel is an important problem in biophysics and drug design.
      Brownian dynamics simulations are large-scale interacting particle computer
      simulations for modeling ion channel permeation but can be computationally
      prohibitive. In this paper, we show the somewhat surprising result that a small
      dimensional semi-Markov model can generate events (such as conduction events and
      dwell times at binding sites in the protein) that are statistically
      indistinguishable from brownian dynamics computer simulation. This approach
      enables the use of extrapolation techniques to predict channel conduction when
      performing the actual brownian dynamics simulation that is computationally
      intractable. Numerical studies on the simulation of gramicidin A ion channels are
      presented.

PMID- 21071817
TI  - Controllable oxygen vacancies to enhance resistive switching performance in a
      ZrO2-based RRAM with embedded Mo layer.
AB  - In this study, the resistive switching characteristics of a ZrO(2)-based memory
      film with an embedded Mo layer are investigated. The experimental results show
      that the forming process can be removed by inserting an embedded Mo metal layer
      within ZrO(2) via a post-annealing process. The excellent memory performance,
      which includes lower operation voltage (<1.5 V), good endurance (>10(3) cycles),
      a stubborn nondestructive readout property (>10(4) s), and long retention time
      (>10(7) s), is also demonstrated. Moreover, high-speed operation (10 ns) can be
      successively maintained over 10(3) cycles without any operational errors observed
      in this memory device. Due to the interface layer induced by the Ti top
      electrode, the formation and rupture of conducting filaments are suggested to
      occur near the Ti/ZrO(2) interface. The oxygen vacancies induced by the embedded
      Mo can enhance the formation of conducting filaments and further improve the
      switching characteristics in ZrO(2)-based devices.

PMID- 21071816
TI  - Environmental cadmium and breast cancer risk.
AB  - Breast cancer is the most prevalent women's cancer, with an age-adjusted
      incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic
      pollutant with multiple biological effects, has been reported to be associated
      with breast cancer in one US regional case-control study. We examined the
      association of breast cancer with urinary cadmium (UCd), in a case-control sample
      of women living on Long Island (LI), NY (100 with breast cancer and 98 without),
      a region with an especially high rate of breast cancer (142.7 per 100,000 in
      Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92
      with breast cancer and 2,884 without). In a multivariable logistic model, both
      samples showed a significant trend for increased odds of breast cancer across
      increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in
      the lowest quartile, LI women in the highest quartile had increased risk for
      breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest
      quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89,
      5.52, respectively). Further research is warranted on the impact of environmental
      cadmium on breast cancer risk in specific populations and on identifying the
      underlying molecular mechanisms.

PMID- 21071818
TI  - Solar harvest.

PMID- 21071819
TI  - Magnetic films on nanoperforated templates: a route towards percolated
      perpendicular media.
AB  - We present a study on the magnetization reversal in Co/Pt multilayer films with
      an out-of-plane easy axis of magnetization deposited onto substrates with densely
      distributed perforations with an average period as small as 34 nm. Deposition of
      magnetic Co/Pt multilayers onto the nanoperforated surface results in an array of
      magnetic nanodots surrounded by a continuous magnetic film. Following the
      evolution of the magnetic domain pattern in the system, we suggest that domain
      walls are pinned on structural inhomogeneities given by the underlying
      nanoperforated template. Furthermore, a series of micromagnetic simulations was
      performed in order to understand the modification of the pinning strength of
      domain walls due to the magnetic interaction between nanodots and the surrounding
      film. The results of the simulations show that magnetic exchange coupling between
      the nanodots and the surrounding film strongly influences the pinning behavior of
      the magnetic domain walls which can be optimized to provide maximal pinning.

PMID- 21071820
TI  - One-pot synthesis of biocompatible Te@phenol formaldehyde resin core-shell
      nanowires with uniform size and unique fluorescent properties by a synergized
      soft-hard template process.
AB  - One-pot hydrothermal process has been developed to synthesize uniform Te@phenol
      formaldehyde resin core-shell nanowires with unique fluorescent properties. A
      synergistic soft-hard template mechanism has been proposed to explain the
      formation of the core-shell nanowires. The Te@phenol formaldehyde resin core
      shell nanowires display unique fluorescent properties, which give strong
      luminescent emission in the blue-violet and green regions with excitation
      wavelengths of 270 nm and 402 nm, respectively.

PMID- 21071821
TI  - Sustained smooth dynamics in short-sleeved nanobearings based on double-walled
      carbon nanotubes.
AB  - We carry out a molecular dynamics study of nanobearings based on double-walled
      carbon nanotubes with a short rotating outer tube. A (4, 4)/(9, 9) bearing
      configuration shows peculiar stabilization of rotational motion at certain values
      of angular velocities. The observed trend is found at those values of initial
      angular velocities (in the current context, 0.8-1.5 rad ps(-1)) which denote a
      transitional regime between nearly frictionless operation at low initial angular
      speeds and decaying performance at high initial angular velocities. With the use
      of detailed 'principal components analysis', we find that the energy dissipation
      occurs mainly due to the excitation of wavy modes in the inner tube of the
      bearing. It is also proposed that wavy deformation is facilitated by the
      actuation of axial translation of the outer tube, which acts as an energy
      channelling mode. Hence, we find that the absence of dissipative wavy modes
      results in sustained smooth rotational dynamics of the nanobearing at low
      temperature.

PMID- 21071822
TI  - Two-dimensional gradient Ag nanoparticle assemblies: multiscale fabrication and
      SERS applications.
AB  - We report a novel method for fabricating silver nanoparticle assemblies with a
      featured gradient of spatial organizations. The unique step is to generate a
      gradient of deposit mass by dynamical deposition on a mask-covered substrate with
      a collimated cluster beam in oblique incidence. Then such gradient can be
      translated to the gradients of sizes or number densities of the nanoparticles
      separately, depending on the nature of the substrate surface. Multiscale
      gradients are implemented from mesoscopic to macroscopic. One-chip rapid
      detection of the optimal structure for surface enhanced Raman scattering (SERS)
      is achieved on the gradient assembly with particle number densities.

PMID- 21071823
TI  - Ordered array of self-assembled SiC nanocrystals fabricated by selective oxide
      desorption and nanosphere lithography.
AB  - We have developed a novel technique based on the selective desorption of an oxide
      film in order to grow ordered arrays of silicon carbide nanocrystals on a silicon
      surface. These nanocrystals form as a byproduct of void nucleation in the oxide
      during the high-temperature vacuum annealing of silicon, a process which normally
      produces a random distribution of nanocrystals across the silicon surface after
      its oxide layer has been fully desorbed. By the pre-deposition of a thin layer of
      excess silicon on the oxide surface through a patterned lithography mask, site
      specific nucleation of voids in the silicon oxide can instead be achieved during
      the annealing step, leading to the growth of silicon carbide nanocrystals in
      regular patterns over the silicon surface.

PMID- 21071824
TI  - C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by
      modulation of autophagy.
AB  - Autophagy, an evolutionally conserved intracellular process degrading cytoplasmic
      proteins and organelles for recycling, has become one of the most remarkable
      strategies applied in cancer research. The fullerene C60 nanoparticle (nC60) has
      been shown to induce autophagy and sensitize chemotherapeutic killing of cancer
      cells, but the details still remain unknown. Here we show that a water-dispersed
      nanoparticle solution of derivatized fullerene C60, C60(Nd) nanoparticles
      (nC60(Nd)), has greater potential in inducing autophagy and sensitizing
      chemotherapeutic killing of both normal and drug-resistant cancer cells than nC60
      does in an autophagy-dependent fashion. Additionally we further demonstrated that
      autophagy induced by nC60/C60(Nd) and Rapamycin had completely different roles in
      cancer chemotherapy. Our results, for the first time, revealed a novel and more
      potent derivative of the C60 nanoparticle in enhancing the cytotoxicity of
      chemotherapeutic agents and reducing drug resistance through autophagy
      modulation, which may ultimately lead to novel therapeutic strategies in cancer
      therapy.

PMID- 21071825
TI  - Emitter spacing effects on field emission properties of laser-treated single
      walled carbon nanotube buckypapers.
AB  - Carbon nanotube (CNT) emitters on buckypaper were activated by laser treatment
      and their field emission properties were investigated. The pristine buckypapers
      and CNT emitters' height, diameter, and spacing were characterized through
      optical analysis. The emitter spacing directly impacted the emission results when
      the laser power and treatment times were fixed. The increasing emitter density
      increased the enhanced field emission current and luminance. However, a
      continuous and excessive increase of emitter density with spacing reduction
      generated the screening effect. As a result, the extended screening effect from
      the smaller spacing eventually crippled the field emission effectiveness.
      Luminance intensity and uniformity of field emission suggest that the highly
      effective buckypaper will have a density of 2500 emission spots cm(-2), which
      presents an effective field enhancement factor of 3721 and a moderated screening
      effect of 0.005. Proper laser treatment is an effective post-treatment process
      for optimizing field emission, luminance, and durability performance for
      buckypaper cold cathodes.

PMID- 21071826
TI  - Organic photovoltaics: principles and techniques for nanometre scale
      characterization.
AB  - The photoconversion efficiency of state-of-the-art organic solar cells has
      experienced a remarkable increase in the last few years, with reported certified
      efficiency values of up to 8.3%. This increase has been due to an improved
      understanding of the underlying physics, synthetic discovery and the realization
      of the pivotal role that morphological optimization plays. Advances in nanometre
      scale characterization have underpinned all three factors. Here we give an
      overview of the current understanding of the fundamental processes in organic
      photovoltaic devices, on optimization considerations and on recent developments
      in nanometre scale measuring techniques. Finally, recommendations for future
      developments from the perspective of characterization techniques are set forth.

PMID- 21071827
TI  - Graphoepitaxial assembly of asymmetric ternary blends of block copolymers and
      homopolymers.
AB  - Ternary blends of cylinder-forming polystyrene-block-poly(methyl methacrylate)
      block copolymers and polystyrene and poly(methyl methacrylate) homopolymers were
      assembled in trench features of constant width. Increasing the fraction of
      homopolymer in the blend increased the spacing and size of block copolymer
      domains, which were oriented perpendicular to the substrate to form a hexagonal
      lattice within the trench. The number of rows of cylinders within the trench was
      controlled by the blend composition. Depending on the domain size and spacing,
      the hexagonal lattice was stretched or compressed perpendicular to the trench
      walls but not perturbed parallel to the walls, indicating a decoupling of the
      perturbation in the perpendicular and parallel directions. The row spacing was
      uniform across the trench as a function of position from the trench wall. The
      results are compared with an analytical model and with Monte Carlo simulations.

PMID- 21071828
TI  - Stochastic analysis of heart rate variability and its relation to
      echocardiography parameters in hypertrophic cardiomyopathy patients.
AB  - The heart rate variability of 10 healthy males (age 26 - 4/+ 3 y) and 49 patients
      with hypertrophic cardiomyopathy (HCM) (25 males, 24 females, age 29.5 - 11.5/+
      10.5 y) was studied. We applied Kramers-Moyal expansion to extract the drift and
      diffusion terms of the Langevin equation for the RR interval time series. These
      terms may be used for a stochastic reconstruction of the time series and for
      description of the properties of heart rate variability. New parameters
      characterizing the diffusion term are proposed: the coefficients of the linear
      fit to the left (LCF) and right (RCF) branch of the dependence of the diffusion
      term on the rescaled heart rate. Relations of the new parameters to classical
      echocardiography parameters were studied. Using the relation between the
      difference LCF-RCF and the left ventricular systolic diameter, the HCM patients
      studied were divided into three groups. In addition, comparison of the properties
      of the heart rate variability in the HCM group with that obtained for the healthy
      young men showed that the parameter LCF-RCF may be treated as a measure of the
      effect of HCM on heart rate variability and may have diagnostic value.

PMID- 21071829
TI  - Augmented photoplethysmographic low frequency waves at the onset of endotoxic
      shock in rabbits.
AB  - A rabbit model of endotoxaemia was employed to study the regional changes in
      photoplethysmogram (PPG) waveform and its low frequency fluctuations, and how
      they are related to the physiological events during the time course of endotoxic
      shock. Endotoxin (1 mg kg(-1) lipopolysaccharide) was injected into eight
      anaesthetized and mechanically ventilated rabbits. The 90 min monitoring period
      was divided into six stages, with the onset of hypotension separating the first
      three (EDTX1-3) and last three (HYPO1-3) stages. The most significant finding was
      a substantial but transient elevation in sympathetic-related toe PPG variability
      (PPGV) spectral power in EDTX3 and HYPO1 (P < 0.01 versus EDTX1). The group
      average response showed that the rapid rise started 15 min before and peaked at
      the onset of hypotension, which indicated a surge in sympathetic vasomotor
      activity that preceded the decompensatory blood pressure fall. Ear skin
      vasoconstriction was evident by a marked and sustained fall in ear PPG amplitude
      along with a decrease in ear skin temperature at the onset of hypotension, during
      which the sympathetic-related ear PPGV spectral power was elevated (P < 0.01,
      HYPO1 versus EDTX1). The results demonstrate the value of PPGV in characterizing
      regional vascular control and provide important insights into the physiological
      mechanisms of endotoxic shock.

PMID- 21071830
TI  - AASM standards of practice compliant validation of actigraphic sleep analysis
      from SOMNOwatchTM versus polysomnographic sleep diagnostics shows high conformity
      also among subjects with sleep disordered breathing.
AB  - In recent AASM practice, parameter actimetry is cited to measure total sleep time
      in obstructive sleep apnoea patients, when polysomnography is not available. An
      actigraph was therefore compared to polysomnographic data in 28 subjects with
      known sleep disordered breathing. Total sleep time (TST), sleep period time
      (SPT), sleep efficiency (SE), sustained sleep efficiency (SSE), sleep onset
      latency (SL) and sleep/wake pattern were compared to gold standard
      polysomnography. The results of an epoch-by-epoch comparison of sleep/wake from
      actigraphy to sleep stages from polysomnography gave a sensitivity of 90.2%, a
      specificity of 95.2% and an overall accuracy of 85.9%. Correlations were
      moderately strong for SE (0.71, p < 0.001) and SSE (0.65, p < 0.001) and high for
      TST (0.89, p < 0.001), SPT (0.91, p < 0.001) and SL (0.89, p < 0.001). It was
      concluded that actigraphy is not identical with PSG recording but gives good
      results in sleep/wake patterns and predicting TST, SPT, SSE, SE and SL also in
      sleep apnoea patients not suffering from other sleep disorders. The difficult
      detection of correct sleep onset causes SSE and SL to be less predictable.
      Therefore a 15-epoch criterion was introduced and resulted in high correlation of
      0.89 for sleep latency, but has to be tested on a bigger population.

PMID- 21071831
TI  - The fluid mechanics of root canal irrigation.
AB  - Root canal treatment is a common dental operation aimed at removing the contents
      of the geometrically complex canal chambers within teeth; its purpose is to
      remove diseased or infected tissue. The complex chamber is first enlarged and
      shaped by instruments to a size sufficient to deliver antibacterial fluids. These
      irrigants help to dissolve dying tissue, disinfect the canal walls and space and
      flush out debris. The effectiveness of the procedure is limited by access to the
      canal terminus. Endodontic research is focused on finding the instruments and
      clinical procedures that might improve success rates by more effectively reaching
      the apical anatomy. The individual factors affecting treatment outcome have not
      been unequivocally deciphered, partly because of the difficulty in isolating them
      and in making the link between simplified, general experimental models and the
      complex biological objects that are teeth. Explicitly considering the physical
      processes within the root canal can contribute to the resolution of these
      problems. The central problem is one of fluid motion in a confined geometry,
      which makes the dispersion and mixing of irrigant more difficult because of the
      absence of turbulence over much of the canal volume. The effects of treatments
      can be understood through the use of scale models, mathematical modelling and
      numerical computations. A particular concern in treatment is that caustic
      irrigant may penetrate beyond the root canal, causing chemical damage to the
      jawbone. In fact, a stagnation plane exists beyond the needle tip, which the
      irrigant cannot penetrate. The goal is therefore to shift the stagnation plane
      apically to be coincident with the canal terminus without extending beyond it.
      Needle design may solve some of the problems but the best design for irrigant
      penetration conflicts with that for optimal removal of the bacterial biofilm from
      the canal wall. Both irrigant penetration and biofilm removal may be improved
      through canal fluid agitation using a closely fitting instrument or by sonic or
      ultrasonic activation. This review highlights a way forward by understanding the
      physical processes involved through physical models, mathematical modelling and
      numerical computations.

PMID- 21071832
TI  - An altered method of feeding RNAi that knocks down multiple genes simultaneously
      in the nematode Caenorhabditis elegans.
AB  - In reverse genetics, RNA interference (RNAi) which is substitutable for gene
      disruption, is an outstanding method for knockdown of a gene's function. In
      Caenorhabditis elegans, feeding RNAi is most convenient, but this RNAi is not
      suitable for knockdown of multiple genes. Hence, we attempted to establish an
      efficient method of feeding RNAi for multiple knockdown. We produced bacteria
      yielding three distinct double-stranded RNAs bound to one another, and fed those
      bacteria to C. elegans. Quantitative RT-PCR and observation of phenotypes
      indicated that our method is much more efficient than the traditional one. Our
      method is useful for investigating genes' functions in C. elegans.

PMID- 21071833
TI  - Novel screening method for potential skin-whitening compounds by a luciferase
      reporter assay.
AB  - Measurement of the melanin content by using B16 melanoma cells is generally
      applied to find novel skin-whitening agents. However, this measurement method
      using B16 melanoma cells has such disadvantages, as the time taken, its
      sensitivity, and troublesomeness. We therefore attempted in the present study to
      establish a reporter assay system by measuring the tyrosinase promoter activity
      to use for convenient, high-throughput screening of new melanogenesis inhibitors.
      We first confirmed the validity of this reporter assay system by using such known
      skin-whitening agents, as arbutin, sulforaphane, and theaflavin 3,3'-digallate.
      We then compared the effect of 56 compounds on the tyrosinase promoter activity
      to test this reporter assay system. Carnosol, and rottlerin strongly inhibited
      the tyrosinase promoter activity. Moreover, carnosol and rottlerin decreased
      melanin synthesis and tyrosinase expression in a dose-dependent manner when using
      B16 melanoma cells. These results indicate this new luciferase reported assay
      system to be an effective and convenient method for screening potential skin
      whitening compounds.

PMID- 21071834
TI  - Repeated oral administration of a squeezed ginger (Zingiber officinale) extract
      augmented the serum corticosterone level and had anti-inflammatory properties.
AB  - We investigated the ability of a ginger extract to induce an immune response in
      RAW 264 cells and after a repeated oral administration to mice. The squeezed
      ginger extract augmented the production of tumor necrosis factor-alpha,
      interleukin-6, and monocyte chemotactic protein-1 when added to RAW 264 cells.
      This extract was collected as its ethanol-insoluble fraction. The oral
      administration of the squeezed ginger extract or its ethanol-insoluble fraction
      once or twice to mice also augmented the tumor necrosis factor-alpha production
      in peritoneal cells; however, its long-term administration had the opposite
      effect. The serum corticosterone level had increased after orally administering
      the squeezed ginger extract and was maintained during the administration period.
      Oral administration of the squeezed ginger extract also inhibited arachidonic
      acid-induced ear edema, but its repeated administration was needed to achieve an
      anti-inflammatory effect. These results suggest that the repeated administration
      of the aqueous constituents of ginger augmented the serum corticosterone level
      and that this may have gradually induced anti-inflammatory activity.

PMID- 21071835
TI  - Reduction of blood pressure by soybean saponins, renin inhibitors from soybean,
      in spontaneously hypertensive rats.
AB  - The effect of commercial purified soybean saponin on renin activity and blood
      pressure was investigated. Soybean saponin significantly inhibited human renin in
      vitro with IC(50)=59.9 ug/ml. Orally administered soybean saponin at 80 mg/kg of
      body weight per day to spontaneously hypertensive rats for 8 weeks significantly
      decreased the blood pressure.

PMID- 21071836
TI  - Silymarin attenuated the amyloid beta plaque burden and improved behavioral
      abnormalities in an Alzheimer's disease mouse model.
AB  - Alzheimer's disease (AD) is characterized by progressive cognitive impairment and
      the formation of senile plaques. Silymarin, an extract of milk thistle, has long
      been used as a medicinal herb for liver diseases. Here we report marked
      suppression of amyloid beta-protein (Abeta) fibril formation and neurotoxicity in
      PC12 cells after silymarin treatment in vitro. In vivo studies had indicated a
      significant reduction in brain Abeta deposition and improvement in behavioral
      abnormalities in amyloid precursor protein (APP) transgenic mice that had been
      preventively treated with a powdered diet containing 0.1% silymarin for 6 months.
      The silymarin-treated APP mice also showed less anxiety than the vehicle-treated
      APP mice. These behavioral changes were associated with a decline in Abeta
      oligomer production induced by silymarin intake. These results suggest that
      silymarin is a promising agent for the prevention of AD.

PMID- 21071837
TI  - Evaluation and target validation of indole derivatives as inhibitors of the AcrAB
      TolC efflux pump.
AB  - Indole derivatives 3-amino-6-carboxyl-indole and 3-nitro-6-amino-indole were
      designed and synthesized based on the TolC structure. They proved to have potent
      synergistic antibacterial effects on chloramphenicol, tetracycline, erythromycin,
      and ciprofloxacin against Escherichia coli YD2 and FJ307 with decreased minimal
      inhibitory concentrations (MICs) at 2-64 folds. To research its functional site,
      Escherichia coli BL21(DE3)-3 expressing a target-site mutated TolC was
      constructed by red homologous recombination and the site-directed mutagenesis
      technique. They did not noticeably affect antimicrobial activity against
      BL21(DE3)-3. All the results indicate that these compounds match our design and
      can be developed as efflux pump inhibitors for the AcrAB-TolC efflux pump.

PMID- 21071838
TI  - Identification of a fluorescent compound in the cuticle of the train millipede
      Parafontaria laminata armigera.
AB  - The train millipede (Parafontaria laminata armigera) emits a blue fluorescence
      (lambda(max)=455 nm) under black light (350 nm). The isolated fluorescent
      compound from the cuticle of P. laminata armigera was identified as pterin-6
      carboxylic acid. The structure of this compound was identified by fluorescent,
      HPLC, and mass spectrometric (ESI-ion trap MS) analyses, and then compared with
      an authentic sample.

PMID- 21071839
TI  - Characterization of Paenibacillus curdlanolyticus intracellular xylanase Xyn10B
      encoded by the xyn10B gene.
AB  - The Paenibacillus curdlanolyticus xyn10B gene encoding a family-10 xylanase was
      cloned and expressed in Escherichia coli, and the recombinant enzyme rXyn10B was
      characterized. Immunological analysis suggested that Xyn10B is an intracellular
      enzyme. rXyn10B hydrolyzed birch-wood xylan and xylooligosaccharides to produce
      mainly xylobiose, suggesting that it is an endoxylanase. Its properties were
      significantly different from those of some homologous enzymes.

PMID- 21071840
TI  - Induction of chlorosis, ROs generation and cell death by a toxin isolated from
      Pyricularia oryzae.
AB  - The ethyl acetate extract of the conidia germination fluid from an Avena isolate
      (Br58) of Pyricularia oryzae had chlorosis-inducing activity on oat leaf
      segments. The same activity was also present in the acetone extract of an oatmeal
      agar culture of Br58. Fungal cultures were used for a large-scale preparation. A
      series of acetone and ethyl acetate extraction monitored by chromatography was
      used to isolate an active fraction. The active principle was purified by HPLC. We
      show by NMR and LC/MS that the toxin was an oxidized C18 unsaturated fatty acid
      named Mag-toxin. Mag-toxin induced chlorosis on oat leaf segments incubated in
      the light but not in the dark. Reactive oxygen species (ROS) and cell death were
      induced by Mag-toxin in oat cells. The sub-cellular localization of ROS
      generation induced by the toxin treatment was correlated with the location of
      mitochondria. Interestingly, the induction of ROS generation and cell death by
      Mag-toxin was light-independent.

PMID- 21071841
TI  - Molecular design of fluorescent labeled glycosides as acceptor substrates for
      sialyltransferases.
AB  - A series of dansyl-labeled glycosides with di-, tetra-, and hexasaccharides
      carrying the terminal N-acetyllactosamine (LacNAc) sequence were synthesized as
      acceptor substrates for alpha2,6- and alpha2,3-sialyltransferases. As an
      alternative design, dansyl-labeled LacNAc glycoside carrying a long-spacer linked
      glycan was engineered by replacement of the LacNAc or lactose units with an alkyl
      chain. In addition, we designed a dansyl-labeled bi-antennary LacNAc glycoside as
      an N-linked oligosaccharide mimetic, such as asialo-alpha(1)-acid glycoprotein.
      The kinetic parameters for the transfer reaction of synthesized dansyl-labeled
      glycosides by sialyltransferases were determined by the fluorescent HPLC method.
      The catalytic efficiencies (V(max)/K(m)) of acceptor substrates carrying the
      terminal LacNAc sequence with various length glycans in the array for alpha2,6-
      and alpha2,3-sialyltransferases decreased in a glycan length-dependent manner.
      Furthermore, of the acceptor substrates tested, dansyl-labeled bi-antennary
      LacNAc glycoside displayed the most favorable K(m) value for alpha2,6- and
      alpha2,3-sialyltransferases.

PMID- 21071842
TI  - Molecular characterization of HbCDPK1, an ethephon-induced calcium-dependent
      protein kinase gene of Hevea brasiliensis.
AB  - Calcium-dependent protein kinases (CDPKs), as major primary Ca(2+) sensors, have
      been implicated in the regulation of stress and developmental signals in plants.
      In this study, a novel CDPK gene, designated HbCDPK1, was isolated from Hevea
      brasiliensis. The HbCDPK1 cDNA had 2,400 bp with an open reading frame of 1,671
      bp encoding 556 amino acids, and the deduced HbCDPK1 protein contained four
      characteristic domains identified in CDPKs, showing a high level of sequence
      similarity to CDPKs from other plants. Expression analysis revealed more
      significant accumulation of the transcripts of HbCDPK1 in latex than in the
      leaves, bark, and roots in H. brasiliensis. In addition, transcription of HbCDPK1
      was strongly induced by mechanical wounding, jasmonic acid (JA), and ethephon.
      Recombinant HbCDPK1 was expressed in E. coli, and its activity was assayed. The
      assay indicated that HbCDPK1 had the kinase and Ca(2+)-binding activity in vitro
      as a calcium-dependent protein. The potential roles of the HbCDPK1 are discussed
      as to latex production and rubber biosynthesis.

PMID- 21071843
TI  - Characterization and analysis of novel carboxyl/cholinesterase genes possessing
      the Thr-316 motif in the silkworm, Bombyx mori.
AB  - Juvenile hormone esterases (JHEs) function in juvenile hormone (JH) degradation.
      In the silkworm, Bombyx mori, we have characterized authentic JHE (Bmjhe) and
      five other carboxyl/cholinesterase (CCE) genes (Bmcce-1 to -5) with GQSAG, a
      motif sequence of JHE. But none of the genes appeared to function in vivo as a
      JHE, except for Bmjhe. Recently it was reported that the GQSAG motif might be
      dispensable, and that the Thr-316 residue has functional significance for JHE
      activity. On the basis of these findings, we identified two novel JHE candidates,
      Bmcce-6 and Bmcce-7, that lack GQSAG but possess Thr-316. In the CCE phylogenetic
      tree, BmCCE-6 was close to the lepidopteran JHE cluster, while BmCCE-7
      constituted the same cluster as pheromone-degrading esterases. The developmental
      expression profiles were different among Bmjhe, Bmcce-6, and Bmcce-7. None of the
      proteins hydrolyzed JH in vitro. Our results suggest that only one CCE (BmJHE)
      functions as JHE in the silkworm.

PMID- 21071844
TI  - Use of a Gluconobacter frateurii mutant to prevent dihydroxyacetone accumulation
      during glyceric acid production from glycerol.
AB  - To prevent dihydroxyacetone (DHA) by-production during glyceric acid (GA)
      production from glycerol using Gluconobacter frateurii, we used a G. frateurii
      THD32 mutant, DeltasldA, in which the glycerol dehydrogenase subunit-encoding
      gene (sldA) was disrupted, but DeltasldA grew much more slowly than the wild
      type, growth starting after a lag of 3 d under the same culture conditions. The
      addition of 1% w/v D-sorbitol to the medium improved both the growth and the GA
      productivity of the mutant, and DeltasldA produced 89.1 g/l GA during 4 d of
      incubation without DHA accumulation.

PMID- 21071845
TI  - Characterization of sulfhydryl heterogeneity in human serum albumin and
      recombinant human serum albumin for clinical use.
AB  - Since human serum albumin has one sulfhydryl group and 17 disulfides, reactive
      sulfhydryl groups give rise to heterogeneity. The present paper presents a
      comparison of sulfhydryl heterogeneity in human serum albumin and recombinant
      human serum albumin for clinical use. Low molecular weight sulfhydryl compounds
      were identified from both sources. The recombinant albumin had a much higher
      sulfhydryl content than plasma serum albumin.

PMID- 21071846
TI  - Construction and characterization of a fluorescent sendai virus carrying the gene
      for envelope fusion protein fused with enhanced green fluorescent protein.
AB  - Sendai virus (SeV) is an enveloped virus with a non-segmented negative-strand RNA
      genome. SeV envelope fusion (F) glycoproteins play crucial roles in the viral
      life cycle in processes such as viral binding, assembly, and budding. In this
      study, we developed a viable recombinant SeV designated F-EGFP SeV/DeltaF, in
      which the F protein was replaced by an F protein fused to EGFP at the carboxyl
      terminus. Living infected cells of the recombinant virus were directly visualized
      by green fluorescence. The addition of EGFP to the F protein maintained the
      activities of the F protein in terms of intracellular transport to the plasma
      membrane via the ER and the Golgi apparatus and fusion activity in the infected
      cells. These results suggest that this fluorescent SeV is a useful tool for
      studying the viral binding, assembly, and budding mechanisms of F proteins and
      the SeV life cycle in living infected cells.

PMID- 21071847
TI  - Characterization of acetohydroxyacid synthase I from Escherichia coli K-12 and
      identification of its inhibitors.
AB  - The first step in branched-chain amino acid biosynthesis is catalyzed by
      acetohydroxyacid synthase (EC 2.2.1.6). This reaction involves decarboxylation of
      pyruvate followed by condensation with either an additional pyruvate molecule or
      with 2-oxobutyrate. The enzyme requires three cofactors, thiamine diphosphate
      (ThDP), a divalent ion, and flavin adenine dinucleotide (FAD). Escherichia coli
      contains three active isoenzymes, and acetohydroxyacid synthase I (AHAS I) large
      subunit is encoded by the ilvB gene. In this study, the ilvB gene from E. coli K
      12 was cloned into expression vector pETDuet-1, and was expressed in E. coli BL21
      (DH3). The purified protein was identified on a 12% SDS-PAGE gel as a single band
      with a mass of 65 kDa. The optimum temperature, buffer, and pH for E. coli K-12
      AHAS I were 37  degrees C, potassium phosphate buffer, and 7.5. Km values for E.
      coli K-12 AHAS I binding to pyruvate, Mg(+2), ThDP, and FAD were 4.15, 1.26, 0.2
      mM, and 0.61 uM respectively. Inhibition of purified AHAS I protein was
      determined with herbicides and new compounds.

PMID- 21071848
TI  - GC-MS based metabolite profiling of rice Koji fermentation by various fungi.
AB  - In this study, Aspergillus kawachii, Aspergillus oryzae, and Rhizopus sp., were
      utilized for rice Koji fermentation, and the metabolites were analyzed in a time
      dependent manner by gas chromatography-mass spectrometry. On Principal Component
      Analysis, the metabolite patterns were clearly distinguished based on the fungi
      species. This approach revealed that the quantities of glucose, galactose, and
      glycerol gradually increased as a function of fermentation time in all trials
      rice Koji fermentation. The time-dependent changes of these metabolites showed
      significant increases in glucose in the A. oryzae-treated rice, and in glycerol
      and galactose in the A. kawachii-treated rice. In addition, glycolysis-related
      enzyme activities were correlated with the changes in these metabolites. The
      results indicate that time-dependent metabolite production has the potential to
      be a valuable tool in selecting inoculant fungi and the optimal fermentation time
      for rice koji.

PMID- 21071849
TI  - A simple set of plasmids for the production of transgenic plants.
AB  - A new set of plasmids for plant transgenic studies was developed. Its strong
      point is that independent gene cassettes are connected within one binary vector
      by the restriction endonuclease-based technique only. Using the set, two
      overexpressing cassettes and three RNA interference (RNAi) cassettes were
      successfully introduced into rice. Our plasmid set is useful for producing
      commercial transgenic plants, especially in the case of rice.

PMID- 21071850
TI  - Comparative biochemical characterization of two GroEL homologs from the
      cyanobacterium Synechococcus elongatus PCC 7942.
AB  - Unlike Escherichia coli, cyanobacteria generally contain two GroEL homologs. The
      chaperone function of cyanobacterial GroELs was examined in vitro for the first
      time with GroEL1 and GroEL2 of Synechococcus elongatus PCC 7942. Both GroELs
      prevented aggregation of heat-denatured proteins. The ATPase activity of GroEL1
      was approximately one-sixth that of Escherichia coli GroEL, while that of GroEL2
      was insignificant. The activities of both GroELs were enhanced by GroES, while
      that of Escherichia coli GroEL was suppressed. The ATPase activity of GroEL1 was
      greatly enhanced in the presence of GroEL2, but the folding activities of GroEL1
      and GroEL2 were much lower than that of Escherichia coli GroEL, regardless of the
      co-presence of the counterpart or GroES. Both native and recombinant GroEL1 forms
      a tetradecamer like Escherichia coli GroEL, while GroEL2 forms a heptamer or
      dimer, but the GroEL1 and GroEL2 oligomers were extremely unstable. In sum, we
      concluded that the cyanobacterial GroELs are mutually distinct and different from
      Escherichia coli GroEL.

PMID- 21071851
TI  - Arabidopsis seedlings over-accumulated indole-3-acetic acid in response to
      aminooxyacetic acid.
AB  - Previously we identified aminooxy compounds as auxin biosynthesis inhibitors. One
      of the compounds, aminooxyacetic acid (AOA) inhibited indole-3-acetic acid (IAA)
      biosynthesis in rice and tomato. Here, we found that AOA induced auxin over
      accumulation in Arabidopsis. The results suggest that auxin-related metabolic
      pathways are divergent among these plant species.

PMID- 21071852
TI  - Tryptophan boost caused by senescence occurred independently of cytoplasmic
      glutamine synthetase.
AB  - We examined to determine whether senescence-induced tryptophan levels are
      positively associated with levels of glutamine synthetase (GS1), the initial
      enzyme in tryptophan biosynthesis. We generated transgenic rice plants in which
      GS1 was suppressed by RNA interference technology. The transgenic line showed a
      dramatic decrease in GS1 protein and glutamine content, but the levels of
      tryptophan and mRNA of the key tryptophan biosynthetic genes upon senescence were
      comparable to those of the wild type.

PMID- 21071853
TI  - Chitosan-induced stomatal closure accompanied by peroxidase-mediated reactive
      oxygen species production in Arabidopsis.
AB  - Chitosan induced stomatal closure in wild type-plants and NADPH oxidase knock-out
      mutants (atrbohD atrbohF), and reactive oxygen species (ROS) production in wild
      type guard cells. Closure and production were completely abolished by catalase
      and a peroxidase inhibitor. These results indicate that chitosan induces ROS
      production mediated by peroxidase, resulting in stomatal closure.

PMID- 21071854
TI  - Distribution and biosynthesis of 20-hydroxyecdysone in plants of Achyranthes
      japonica Nakai.
AB  - There is increasing interest in phytoecdysteroids (PEs) because of their
      potential role in plant defense against insects. To understand the mechanism
      regulating their levels in plants, the fluctuation, distribution, and
      biosynthesis of PE 20-hydroxyecdysone (20E) examined in Achyranthes japonica. The
      total amount of 20E per individual plant initially remained at a constant level,
      and increased markedly after the first leaf pair (LP) stage, while the
      concentration of 20E in a given plant decreased rapidly during vegetative growth.
      In addition, the incorporation of [2-(14)C]-mevalonic acid into 20E did not
      differ significantly depending on plant organs and developmental stages,
      suggesting that biosynthesis of 20E is not restricted to particular organs or
      growth stages.

PMID- 21071855
TI  - Effect of randomly interesterified triacylglycerol containing medium- and long
      chain fatty acids on hepatic fatty acid oxidation after a single administration
      to rats.
AB  - MLCTs, which are randomly interesterified triacylglycerol containing medium- and
      long-chain fatty acids in the same glycerol molecule, showed significantly higher
      acyl-CoA dehydrogenase activity when measured by using butyryl-CoA, octanoyl-CoA,
      and palmitoyl-CoA as substrates than long-chain triacylglycerol one hour after a
      single administration to rats. These results suggest that not only medium-chain
      fatty acid oxidation, but also long-chain fatty acid oxidation were increased in
      the liver of rats administered with MLCT.

PMID- 21071856
TI  - JBIR-66, a new metabolite isolated from tunicate-derived Saccharopolyspora sp.
      SS081219JE-28.
AB  - In the course of our chemical screening program for new secondary metabolites, we
      isolated a new compound JBIR-66 (1) from the culture broth of the tunicate
      derived actinomycete, Saccharopolyspora sp. SS081219JE-28. The structure of 1 was
      determined to be (3Z,6E,8E)-N-(4-acetamido-3-hydroxybutyl)-2-hydroxy-4,8
      dimethylundeca-3,6,8-trienamide on the basis of extensive NMR and MS
      spectroscopic data.

PMID- 21071857
TI  - Synthesis of atromentin and its O-alkylated natural products.
AB  - The structure of a long-known natural pigment, atromentin, was established by a
      total synthesis based on double Suzuki-Miyaura coupling and by a single-crystal X
      ray analysis of the synthetic sample thereby obtained. A similar strategy
      including ceric ammonium nitrate (CAN) oxidation was applied to prepare 2-O
      methoxyatromentin and thelephantin I.

PMID- 21071858
TI  - Induction and promotion of flowering by heat-treated catecholamines in Lemna
      paucicostata.
AB  - Alkali- and heat-treated norepinephrine, a catecholamine, induced flowering of
      short-day (SD) plant Lemna paucicostata 151 even under long-day (LD) conditions.
      Flowering induced with a lower concentration of heat-treated norepinephrine was
      promoted under SD conditions but inhibited by a night break. The related
      compounds L-dopa and dopamine also promoted flowering under SD conditions when
      they were heat-treated.

PMID- 21071859
TI  - Sulfite oxidation catalyzed by aa(3)-type cytochrome c oxidase in
      Acidithiobacillus ferrooxidans.
AB  - Sulfite is produced as a toxic intermediate during Acidithiobacillus ferrooxidans
      sulfur oxidation. A. ferrooxidans D3-2, which posseses the highest copper
      bioleaching activity, is more resistant to sulfite than other A. ferrooxidans
      strains, including ATCC 23270. When sulfite oxidase was purified homogeneously
      from strain D3-2, the oxidized and reduced forms of the purified sulfite oxidase
      absorption spectra corresponded to those of A. ferrooxidans aa(3)-type cytochrome
      c oxidase. The confirmed molecular weights of the alpha-subunit (52.5 kDa), the
      beta-subunit (25 kDa), and the gamma-subunit (20 kDa) of the purified sulfite
      oxidase and the N-terminal amino acid sequences of the gamma-subunit of sulfite
      oxidase (AAKKG) corresponded to those of A. ferrooxidans ATCC 23270 cytochrome c
      oxidase. The sulfite oxidase activities of the iron- and sulfur-grown A.
      ferrooxidans D3-2 were much higher than those cytochrome c oxidases purified from
      A. ferrooxidans strains ATCC 23270, MON-1 and AP19-3. The activities of sulfite
      oxidase purified from iron- and sulfur-grown strain D3-2 were completely
      inhibited by an antibody raised against a purified A. ferrooxidans MON-1 aa(3)
      type cytochrome c oxidase. This is the first report to indicate that aa(3)-type
      cytochrome c oxidase catalyzed sulfite oxidation in A. ferrooxidans.

PMID- 21071860
TI  - Physiological effects of dietary PIPS soybean-derived phospholipid in obese
      zucker (fa/fa) rats.
AB  - The effects of soybean-derived phospholipid, PIPS NAGASE(TM) (PIPS), on obesity
      induced diseases were studied in obese rats. Dietary PIPS alleviated hepatomegaly
      and fatty liver in the rats. These effects were attributable to reduced
      lipogenesis and enhanced lipolysis in the liver. The results suggest that PIPS
      can be useful as a dietary component that would reduce the risk of lifestyle
      related diseases.

PMID- 21071861
TI  - Agrobacterium tumefaciens-mediated transformation of the vegetative dikaryotic
      mycelium of the cultivated mushroom Flammulina velutipes.
AB  - Agrobacterium tumefaciens was used to transform the vegetative dikaryotic
      mycelium of Flammulina velutipes using a hygromycin B resistance gene as
      selectable marker. The gene coding for urogen III methyltransferase (cob) was
      introduced into F. velutipes dikaryotic cells. The resulting transformant cells
      generated a bright red fluorescence, indicating that cob is promising as a
      reporter gene in F. velutipes.

PMID- 21071862
TI  - Inhibition of plasma hyaluronan-binding protein autoactivation by laccaic acid.
AB  - Plasma hyaluronan-binding protein (PHBP) is a serine protease implicated in
      proteolysis under inflammatory conditions. We identified laccaic acid, a widely
      used food coloring from scale insects, as a potent inhibitor of the protease in
      terms of both autoactivation of the PHBP proenzyme (IC(50) = 0.35-0.55 ug/ml) and
      the catalytic activity of the active enzyme (IC(50) = 1.1 ug/ml).

PMID- 21071863
TI  - Stability profiles of nepenthesin in urea and guanidine hydrochloride: comparison
      with porcine pepsin A.
AB  - Nepenthesin, an aspartic endopeptidase from the pitcher fluid of Nepenthes, was
      found to be markedly less stable than porcine pepsin A when treated with urea or
      guanidine hydrochloride. This is in sharp contrast with its remarkably high
      pH/temperature stability as compared with porcine pepsin A. No protein with such
      a stability profile has been reported to date.

PMID- 21071864
TI  - Mixed-species biofilm formation by direct cell-cell contact between brewing
      yeasts and lactic acid bacteria.
AB  - Mixed-species biofilm was remarkably formed in a static co-culture of
      Lactobacillus plantarum ML11-11 and Saccharomyces cerevisiae Y11-43 isolated from
      brewing samples of Fukuyama pot vinegar. Mixed-species biofilm is probably formed
      by direct cell-cell contact between ML11-11 and S. cerevisiae including Y11-43
      and laboratory yeast strains. Scanning electron microscopic observation suggested
      that the mixed-species biofilm had a thick, bi-layer structure.

PMID- 21071865
TI  - Identification and biochemical characterization of a thermostable malate
      dehydrogenase from the mesophile Streptomyces coelicolor A3(2).
AB  - We identified and characterized a malate dehydrogenase from Streptomyces
      coelicolor A3(2) (ScMDH). The molecular mass of ScMDH was 73,353.5 Da with two
      36,675.0 Da subunits as analyzed by matrix-assisted laser-desorption ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS). The detailed kinetic parameters
      of recombinant ScMDH are reported here. Heat inactivation studies showed that
      ScMDH was more thermostable than most MDHs from other organisms, except for a few
      extremely thermophile bacteria. Recombinant ScMDH was highly NAD(+)-specific and
      displayed about 400-fold (k(cat)) and 1,050-fold (k(cat)/K(m)) preferences for
      oxaloacetate reduction over malate oxidation. Substrate inhibition studies showed
      that ScMDH activity was inhibited by excess oxaloacetate (K(i)=5.8 mM) and excess
      L-malate (K(i)=12.8 mM). Moreover, ScMDH activity was not affected by most metal
      ions, but was strongly inhibited by Fe(2+) and Zn(2+). Taken together, our
      findings indicate that ScMDH is significantly thermostable and presents a
      remarkably high catalytic efficiency for malate synthesis.

PMID- 21071866
TI  - Estrogenic and anti-estrogenic activities of the Thai traditional herb, Butea
      superba Roxb.
AB  - This study evaluated the estrogenic and antiestrogenic activities of native and
      in vitro hepatic metabolized tuberous extracts of wild Butea superba collected
      from 23 out of the 76 provinces in Thailand by yeast estrogen screening (YES).
      The YES screen used consisted of the human estrogen receptors hERalpha and
      hERbeta and the human transcriptional intermediary factor 2 or human steroid
      receptor coactivator 1, respectively, together with the beta-galactosidase
      expression cassette as the reporter. The relative potency, effectiveness and
      relative inductive efficiency were evaluated by determining the beta
      galactosidase activity (EC(50)) of each tuberous extract in relation to that
      induced by 17beta-estradiol. Six pure compounds isolated from B. superba were
      tested in parallel and exhibited a maximum relative potency compared to 17beta
      estradiol of 15.5% and 5.27% in the respective hERalpha and hERbeta assays.
      Eighteen and seventeen plant extracts were respectively found to interact with
      the hERalpha and hERbeta receptors in the YES assays with higher relative potency
      and relative inductive efficiency with hERbeta than with hERalpha. The selected
      plant extracts tested exhibited antiestrogenic activity. Coincubation with the
      rat liver S9 mixture also elevated the estrogenic potency of these plant
      extracts.

PMID- 21071867
TI  - Gold nanoparticles inhibited the receptor activator of nuclear factor-kappab
      ligand (RANKL)-induced osteoclast formation by acting as an antioxidant.
AB  - Gold nanoparticles inhibited osteoclast (OC) formation induced by the receptor
      activator of nuclear factor-kappaB ligand (RANKL) in bone marrow-derived
      macrophages (BMMs). This was accompanied by a decreased level of tartrate
      resistant alkaline phosphatase (TRAP) and less activation of nuclear factor (NF)
      kappaB. The nanoparticles also reduced the production of reactive oxygen species
      (ROS) in response to RANKL and upregulated RANKL-induced glutathione peroxidase-1
      (Gpx-1), suggesting a role as an antioxidant in the BMM. The inhibitory effects
      on OC formation might have been due to elevated defense against oxidative stress.

PMID- 21071868
TI  - Study of the relationship between changes in lactic acid bacterial cell
      components and stimulation of IL-12 production under salt-stressed conditions.
AB  - One hundred and seventeen strains of plant origin lactic acid bacteria were
      observed to have interleukin (IL)-12 production-inducing activities using mouse
      peritoneal macrophages. Pediococcus pentosaceus (KKM122) was chosen for its
      stable and strong IL-12 production-inducing activity. There was no significant
      difference in IL-12 activity induced by the KKM122 strain grown in culture
      conditions of 0% and 6% NaCl. The cell wall components of cells grown in 6% salt
      condition, however, significantly induced lower IL-12 production as compared with
      those of cells grown in 0% salt condition. Cell wall components enhanced IL-12
      activity by removing cytoplasmic components when KKM122 strain was cultured in 0%
      salt condition. The immunoenhancing factor was mainly present in the cell wall
      components. IL-12 production-inducing activities were dependent on both the
      amount of bacterial cytoplasmic components and the structure of the cell wall
      components under the NaCl concentration in the culture medium.

PMID- 21071869
TI  - Selection of peptide inhibitors of soluble Abeta(1-42) oligomer formation by
      phage display.
AB  - There have been many reports suggesting that soluble oligomers of amyloid beta
      (Abeta) are neurotoxins causing Alzheimer's disease (AD). Although inhibition of
      the soluble oligomerization of Abeta is considered to be effective in the
      treatment of AD, almost all peptide inhibitors have been designed from the beta
      sheet structure (H14-D23) of Abeta(1-42). To obtain more potent peptides than the
      known inhibitors of the soluble-oligomer formation of Abeta(1-42), we performed
      random screening by phage display. After fifth-round panning of a hepta-peptide
      library against soluble Abeta(1-42), novel peptides containing arginine residues
      were enriched. These peptides were found to suppress specifically 37/48 kDa
      oligomer formation and to keep the monomeric form of Abeta(1-42) even after 24 h
      of incubation, as disclosed by SDS-PAGE and size-exclusion chromatography. Thus
      we succeeded in acquiring novel efficient peptides for inhibition of soluble
      37/48 kDa oligomer formation of Abeta(1-42).

PMID- 21071870
TI  - Fluorogenic ribonuclease protection (FRIP) analysis of single nucleotide
      polymorphisms (SNPs) in Japanese Rice (Oryza sativa L.) DNA for cultivar
      discrimination.
AB  - A rapid and easy method to discriminate plant cultivars is indispensable to
      confirm food labeling. We established a fluorogenic ribonuclease protection
      (FRIP) assay to discriminate Japanese rice (Oryza sativa L.) cultivars based on
      single nucleotide polymorphisms (SNPs). The FRIP assay uses a hybridization
      technique between fluorescent probes and the target sequence prepared by run-off
      transcription, but the requirement of two PCR thermocycles is the problem when
      preparing template DNA for run-off transcription from rice genomic DNA. In this
      study, we designed new PCR primers with asymmetric melting temperatures. These
      primers amplified the target SNP marker containing a T7 RNA polymerase promoter
      sequence upstream of the target sequence in a single PCR. Moreover, 100 cultivars
      were discriminated with the patterns of 15 SNPs. The assay can be used as a rapid
      method of analysis to discriminate Japanese rice cultivars.

PMID- 21071871
TI  - Salkowski's reagent test as a primary screening index for functionalities of
      rhizobacteria isolated from wild dipterocarp saplings growing naturally on medium
      strongly acidic tropical peat soil.
AB  - Rhizobacteria isolated from wild dipterocarp saplings in Central Kalimantan,
      Indonesia, were subjected to Salkowski's reagent test, which is often used in
      detecting indolic substances. Among 69 isolates grown in a low-nitrogen medium
      supplemented with L-tryptophan (TRP), culture fluids of 29 strains were positive
      to the test, in which 17 bacteria turned red and other 10 pink. All the red type
      rhizobacteria actively converted TRP into tryptophol (TOL), while some yielded
      indole-3-acetic acid (IAA) with TOL production. They also showed a capacity to
      decompose gallotannin into pyrogallol via gallic acid. On the other hand, an
      active IAA-producing Serratia sp. CK67, and three Fe-solubilizing Burkholderia
      spp. CK28, CK43, and Citrobacter sp. CK42, were all involved in pink type
      rhizobacteria, which were more effective, oxidative TRP-degraders than the red
      type rhizobacteria. Thus, Salkowski's reagent test should be a useful primary
      index in the screening of functional rhizobacteria in peatland ecosystem.

PMID- 21071873
TI  - Beneficial actions of statins in the reduction of atrial fibrillation and
      stabilization and regression of coronary plaques: but how and why?

PMID- 21071874
TI  - Atypical exercise stress myocardial perfusion SPECT imaging in a patient with
      effort angina pectoris.

PMID- 21071875
TI  - Long-term clinical implication of the occurrence of dissociated pulmonary vein
      activities after circumferential left atrial ablation in patients with paroxysmal
      atrial fibrillation.
AB  - BACKGROUND: The incidence and clinical implication of dissociated pulmonary vein
      (PV) electrical activities after circumferential antrum PV ablation for
      paroxysmal atrial fibrillation (AF) remains unclear. METHODS AND RESULTS: A total
      of 196 patients with symptomatic paroxysmal AF who underwent circumferential
      antrum PV ablation were prospectively studied. Dissociated PV electrical
      activities were observed in 101 patients (Group 1), but absent in the remaining
      95 patients (Group 2). There were no significant differences in the baseline
      clinical characteristics between them, except that Group 2 had a higher
      prevalence of hypertension (30 vs. 44%, P = 0.04). After 21.8 +/- 7.9 months of
      follow-up, 148 had no recurrence of AF after the initial procedure. AF recurrence
      rate was significantly higher in Group 2 than in Group 1 (P = 0.023). Relapse of
      PV conduction was the major cause of AF recurrence in both groups (16/16 vs.
      19/23, P = 0.08), and the overall procedural success rate after the redo ablation
      procedure was similar in the 2 groups (90 vs. 86%, P = 0.44). However, the total
      number of patients with non-PV foci was significantly higher in Group 2 than in
      Group 1 (12/95 vs. 2/101, P < 0.01). CONCLUSIONS: Dissociated PV electrical
      activities might identify a subgroup of patients with relatively higher initial
      procedural success with circumferential PV antrum ablation.

PMID- 21071876
TI  - High blood viscosity is closely associated with cigarette smoking and markedly
      reduced by smoking cessation.
AB  - BACKGROUND: Cigarette smoking is an independent risk factor for cardiovascular
      events such as myocardial infarction and stroke. To date, a useful and convenient
      method of predicting such events in smokers has not been established. The
      rheological properties of blood assessed by the microchannel method reflect the
      blood's viscosity and the state of microthrombus formation, which may predict
      cardiovascular thrombotic events. METHODS AND RESULTS: Blood fluidity was
      assessed in 74 smoking patients (54 men, 20 women, mean age 57.9 years) by
      measuring the blood passage time (BPT) in an aliquot (100 ul) of blood using the
      Micro Channel Array Flow Analyzer. BPT was significantly related with smoking
      variables such as daily consumption of tobacco (r = 0.236, P = 0.044), Brinkman's
      index (r = 0.252, P = 0.033), the Fagerstrom Test for Nicotine Dependence (r =
      0.257, P = 0.029), and the score of a self-rating depression scale (r = 0.236, P
      < 0.05). Multivariate regression analysis revealed that an independent BPT
      determinant was daily consumption of tobacco (r = 0.326, P = 0.045). Furthermore,
      smoking cessation markedly decreased BPT from 63.0 s to 49.7 s (P = 0.002) at 3
      months after the start of therapy. CONCLUSIONS: Unfavorable blood rheology is
      closely associated with cigarette smoking and may reflect increased
      cardiovascular risk in smokers. The study results also suggest that such risk can
      be reduced after only 3 months of smoking cessation.

PMID- 21071877
TI  - Localization of latent transforming growth factor-beta binding protein-1 in human
      coronary atherosclerotic plaques.
AB  - BACKGROUND: Transforming growth factor-beta (TGFbeta) and its receptors have been
      detected by immunohistochemistry in the normal vessel wall and in atherosclerotic
      lesions of human coronary arteries. However, TGFbeta is normally secreted as an
      inactive complex associated with a latent TGFbeta-binding protein (LTBP).
      Therefore, detection of TGFbeta antigen only in the arterial wall does not imply
      the activated form of the growth factor. METHODS AND RESULTS: In situ
      hybridization and immunohistochemistry demonstrated LTBP1 mRNA and protein
      expression throughout the media and intima of early coronary artery lesions, with
      the highest levels of protein at the luminal surface. In advanced lesions, LTBP1
      mRNA and protein were detected mainly in regions of high cell density, such as
      the fibrous cap. CONCLUSIONS: Assays of the TGFbeta signalling pathway will be
      required to determine the activity associated with TGFbeta antigen in the vessel
      wall.

PMID- 21071878
TI  - Prospective comparison of the 5 most popular risk scores in clinical use for
      unselected patients with acute coronary syndrome.
AB  - BACKGROUND: A limited number of studies comparing the main risk scores (RS) for
      acute coronary syndromes (ACS) have been conducted and there is a limited number
      of long-term observations of unselected patient cohorts evaluated with the
      various RS. The aim of this study was to validate 5 RS (TIMI STEMI RS, TIMI
      NSTEMI/UA RS, GRACE RS, SIMPLE RS and ZWOLLE RS) in a Polish population and to
      develop a new RS that would specifically predict 1-year mortality in the
      unselected ACS patient cohort. METHODS AND RESULTS: Single-center ACS registry
      analysis with 1-year follow-up of 931 patients and prospective comparison of 5 RS
      was conducted. Creation of an RS was attempted. Risk factors were evaluated in a
      multivariate logistic regression model. The predictive value of the model was
      assessed with evaluation of the area under curve (AUC) in receiver-operating
      characteristic analysis. Twelve independent factors influencing 1-year mortality
      were identified and of them, clerking, physical findings on admission, first ECG
      and myocardial necrosis markers demonstrated sufficiently high predictive value.
      All 5 RS were successfully validated in the target registry and although they all
      displayed high predictive value, the TIMI RS STEMI (AUC = 0.84) and GRACE RS (AUC
      = 0.84) proved superior. CONCLUSIONS: The developed Banach score offers both high
      goodness-of-fit and predictive value and may be used irrespective of ACS type.

PMID- 21071879
TI  - Challenges for kinetic identification of variability associated with genetic
      polymorphisms of transporters.

PMID- 21071880
TI  - Serum resistin levels and cardiovascular events in patients undergoing
      percutaneous coronary intervention.
AB  - AIM: Resistin is an adipocytokine that may link inflammation and
      atherosclerosis.We studied the associations of resistin levels with
      cardiovascular events and restenosis. METHODS: We measured pre-procedural serum
      resistin levels in 140 patients with coronary artery disease undergoing elective
      percutaneous coronary intervention (PCI), of whom 97 had a stent. Restenosis was
      defined as > 50% stenosis at follow-up angiography. Patients were followed for 3
      years for major adverse cardiovascular events (MACE). RESULTS: At 8+/-6 months
      after PCI, reangiography was performed in 94 (67%) patients, of whom 42 had
      restenosis. Between 42 patients with restenosis and 52 without restenosis,
      resistin (4.5+/-2.6 vs. 4.5+/-2.5 ng/mL) and Creactive protein (CRP) (median 0.70
      vs. 0.70 mg/L) levels did not differ. During 3-year follow-up, MACE occurred in
      24 patients (1 death, 21 unstable angina, 2 stroke). Compared with 116 patients
      without MACE, 24 with MACE had higher resistin (5.4+/-2.4 vs. 4.3+/-2.5 ng/mL)
      and CRP (1.30 vs. 0.60 mg/L) levels (p< 0.05). Patients with MACE more often had
      resistin >4.0 ng/mL than without MACE (75% vs. 35%, p< 0.001). Resistin
      correlated with CRP levels (r= 0.31). To clarify the association between MACE and
      resistin, patients were divided into 2 groups by resistin levels. Kaplan-Meier
      analysis showed a lower event-free survival rate in patients with resistin > 4.0
      ng/mL than without it (p< 0.001). On multivariate analysis, resistin, but not
      CRP, was an independent predictor of MACE. The hazard ratio for MACE was 3.6
      (95%CI=1.4-9.2) for resistin > 4.0 ng/mL. CONCLUSION: Serum resistin levels were
      found to be associated with further cardiovascular events in patients undergoing
      PCI.

PMID- 21071881
TI  - Clinical features of normal weight Japanese patients with type 2 diabetes who had
      formerly been obese.
AB  - AIM: Although the mean body mass index (BMI) of Japanese patients with type 2
      diabetes was within the normal range, we have previously shown that approximately
      half of all patients classified as normal weight had been formerly obese. The
      present study examined the clinical features of Japanese type 2 diabetic patients
      who are currently of normal weight but had formerly been obese (NWFO). METHODS:
      Body weight history with selfreported body weight was obtainable for 108 of 114
      type 2 diabetic outpatients who had been regularly attending our department.
      Common carotid artery intimamedia thickness (IMT) was also measured. RESULTS: At
      the time of the examinations, 5 (5%) and 36 (33%) of 108 type 2 diabetic patients
      were lean (BMI <18.5 kg/m(2)) and obese (BMI >=25 kg/m(2)), respectively, whereas
      normal weight (BMI >=18.5-<25 kg/m(2)) was found in 67 (62%) patients. Among 108
      patients, 67 (62%) were normal weight, of which 32 (48%) were formerly obese
      (NWFO). NWFO patients with a mean age of 65 years old at the clinic visit had
      reached their lifetime maximum body weight at age 45 and became diabetic at age
      51 years. Obese patients aged 62 years at the clinic visit became diabetic at age
      50 and had reached their maximum weight at age 51 years. Diabetes duration was 11
      years in patients who had never been obese. Thus, NWFO patients had been exposed
      to obesity-related metabolic abnormalities and/or hyperglycemia for 20 years on
      average whereas obese and never obese patients had been exposed for 11-12 years.
      Although obese patients had higher fasting TG and greater BMI than NWFO, both
      obese and NWFO patients had similarly lower HDL cholesterol levels than those who
      had never been obese; however, there was no difference among the 3 groups in
      diabetic treatment, diabetes duration, HbA1c levels, and prevalence of
      atherosclerotic risk factors, including smokers, users of statins and
      antihypertensive drugs. Carotid max IMT was thicker in NWFO type 2 diabetic
      patients (0.86+/-0.04 mm) than either obese patients (0.78+/-0.03 mm, p=0.041) or
      those who had never been obese (0.78+/-0.02 mm, p=0.046). CONCLUSION: This report
      confirms that approximately half of 108 Japanese type 2 diabetic patients who are
      currently normal weight were formerly obese and shows that these patients had a
      thicker carotid IMT than either obese patients or those who had never been obese.
      Formerly obese diabetic patients who have lost weight and are currently normal
      weight might have been exposed to long-term obesity-related cardiometabolic
      abnormalities and/or hyperglycemia, resulting in increased common carotid IMT. We
      therefore suggest that an improved clinical screening tool would include the
      assessment of body weight history for all Japanese type 2 diabetic patients at
      their first clinic visit.

PMID- 21071882
TI  - Relationship between peripheral arterial disease and incident disability among
      elderly Japanese: the Tsurugaya project.
AB  - AIM: The aim of this study was to investigate whether peripheral arterial disease
      (PAD) is predictive of disability and whether the relationship between PAD and
      disability can be fully explained by baseline physical functions. METHODS: We
      followed for five years 783 Japanese aged 70 years or older without a disability
      at baseline in 2003. We defined participants certificed as requiring long-term
      care as having incident disability. The hazard ratio (HR) and 95% confidence
      interval (95% CI) for incident disability were calculated using the Cox
      proportional hazards model. RESULTS: After adjusting for possible confounders
      other than physical function, the HR of incident disability among participants
      with PAD was 1.86 (95%CI: 1.06 to 3.26).Although the risk was attenuated
      (HR=1.63, 95%CI: 0.92 to 2.86) after adding baseline physical function as a
      covariate, the HR was still high. Furthermore, the relation was not statistically
      significant, but the group with higher physical function and PAD also had a
      higher HR of incident disability than those who had higher physical function
      without PAD. CONCLUSION: PAD is an important predictor of disability even if the
      level of baseline physical function is high.

PMID- 21071883
TI  - Contradictory effects of beta1- and alpha1- aderenergic receptor blockers on
      cardio-ankle vascular stiffness index (CAVI)--CAVI independent of blood pressure.
AB  - AIM: The cardio-ankle vascular stiffness index (CAVI) is a new parameter that
      reflects the stiffness of the aorta, femoral artery and tibial artery as a whole.
      One of its conspicuous features is that CAVI is independent of blood pressure at
      measuring time, theoretically. But, it has not been experimentally proved yet.
      For confirmation, pharmacological studies were performed comparing with brachial
      ankle pulse wave velocity (baPWV). METHODS: Used drugs were a beta1-adrenoceptor
      blocker, metoprorol and an alpha1- adrenoceptor blocker doxazosin. Both were
      administered to 12 healthy volunteer men. CAVI and baPWV were measured every one
      hour for 6 hours using VaSera. RESULTS: When metoprolol (80 mg) was administered
      to 12 healthy volunteer men, systolic blood pressure decreased from 131.4 +/- 4.5
      to 118.3 +/- 4.1 mmHg (mean +/- SE) (p < 0.05) at the 3rd hour, and diastolic
      blood pressure decreased from 85.3 +/- 4.0 to 75.3 +/- 3.0 mm Hg (p < 0.05). baP
      WV decreased from 13.93 +/- 0.46 to 12.46 +/- 0.49 m/sec (p < 0.05),
      significantly, but CAVI did not change (8.16 +/- 0.29 to 8.24 +/- 0.27) (p =
      0.449). DeltabaPWV at each time was significantly correlated with both
      Deltasystolic and Deltadiastolic blood pressures, but DeltaCAVI was not
      correlated with either Deltablood pressure. When doxazosin (4 mg) was
      administered to the same men, systolic blood pressure decreased from 130.2 +/-
      4.6 to 117.2 +/- 4.8 mmHg (p < 0.05) at the 3rd hour. Diastolic blood pressure
      also decreased from 85.1 +/- 4.1 to 74.2 +/- 3.9 mmHg (p < 0.05). baPWV decreased
      from 13.98 +/- 0.68 to 12.25 +/- 0.53 m/sec (p < 0.05), significantly. CAVI also
      decreased from 8.15 +/- 0.28 to 7.18 +/- 0.37 (p < 0.05), significantly.
      CONCLUSION: These results suggested that CAVI was not affected by blood pressure
      at the measuring time directly, but affected by the changes of contractility of
      smooth muscle cells.

PMID- 21071884
TI  - An overview of genetic polymorphisms and pancreatic cancer risk in molecular
      epidemiologic studies.
AB  - BACKGROUND: Although pancreatic cancer has been extensively studied, few risk
      factors have been identified, and no validated biomarkers or screening tools
      exist for early detection in asymptomatic individuals. We present a broad
      overview of molecular epidemiologic studies that have addressed the relationship
      between pancreatic cancer risk and genetic polymorphisms in several candidate
      genes and suggest avenues for future research. METHODS: A comprehensive
      literature search was performed using the PubMed database. RESULTS: Overall,
      individual polymorphisms did not seem to confer great susceptibility to
      pancreatic cancer; however, interactions of polymorphisms in carcinogen
      metabolizing genes, DNA repair genes, and folate-metabolizing genes with smoking,
      diet, and obesity were shown in some studies. The major problem with these
      studies is that, due to small sample sizes, they lack sufficient statistical
      power to explore gene-gene or gene-environment interactions. Another important
      challenge is that the measurement of environmental influence needs to be improved
      to better define gene-environment interaction. It is noteworthy that 2 recent
      genome-wide association studies of pancreatic cancer have reported that variants
      in ABO blood type and in 3 other chromosomal regions are associated with risk for
      this cancer, thus providing new insight into pancreatic cancer etiology.
      CONCLUSIONS: As is the case in other complex diseases, common, low-risk variants
      in different genes may act collectively to confer susceptibility to pancreatic
      cancer in individuals with repeated environmental exposures, such as smoking and
      red meat intake. Clarification of gene-gene and gene-environmental interaction is
      therefore indispensable for future studies. To address these issues, a rigorously
      designed molecular epidemiologic study with a large sample is desirable.

PMID- 21071885
TI  - High-density lipoprotein cholesterol, obesity, and mammographic density in Korean
      women: the Healthy Twin study.
AB  - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is reported to be
      associated with breast cancer risk. To better understand this association, we
      examined the relationship between HDL-C and mammographic density, a putative
      intermediate risk factor for breast cancer. METHODS: The study subjects were 711
      Korean women from the Healthy Twin study. Lipid parameters were assayed
      enzymatically in fresh sera, and percent dense area (PDA) and absolute dense area
      were measured from digital mammograms using a computer-assisted method. RESULTS:
      PDA was positively associated with HDL-C in both premenopausal and postmenopausal
      women in a multivariable-adjusted linear mixed model, but the association did not
      persist when the model was additionally adjusted for body mass index (BMI). BMI
      was inversely associated with PDA, and this association did not change after
      additional adjustment for any lipid parameter. Multivariable-adjusted analysis
      showed that there were significant additive genetic cross-trait correlations
      between PDA and both HDL-C (coefficient, 0.175) and triglyceride (coefficient, 
      0.262). However, those correlations disappeared after additional adjustment for
      BMI. CONCLUSIONS: HDL-C alone is unlikely to increase the risk of breast cancer
      in Korean women, particularly through changes in breast parenchyma that are
      apparent in mammographic density. BMI should be included in studies using
      analytical models where mammographic density is used as an intermediate risk
      factor for breast cancer.

PMID- 21071886
TI  - Expression and function of apoptosis initiator FOXO3 in granulosa cells during
      follicular atresia in pig ovaries.
AB  - In mammalian ovaries, most follicles are lost by atresia before ovulation. It has
      become apparent that the apoptosis of granulosa cells induces follicular atresia.
      Forkhead box O3 (FOXO3), also called FKHRL1 (forkhead in rhabdomyosarcoma-like
      1), is a proapoptotic molecule that belongs to the FOXO subfamily of forkhead
      transcription factors. Foxo3-deficient female mice were reported to be infertile
      because of abnormal ovarian follicular development, but the precise influences of
      FOXO3 on follicular atresia of mature ovary have not been determined. Therefore,
      we examined the expression and function of FOXO3 in porcine ovarian follicles and
      granulosa-derived cells. FOXO3 mRNA levels in granulosa cells of porcine ovaries
      increased during atresia, while FOXO3 protein was abundant in granulosa cells of
      early atretic follicles. By immunohistochemistry, the inner surface area of the
      granulosa layer in early atretic follicles was strongly stained with anti-FOXO3
      antibody. The granulosa cells expressing FOXO3 coincided with apoptotic cells,
      indicating a role of FOXO3 as a proapoptotic factor in granulosa cells of porcine
      ovaries. In porcine (JC-410) and human (KGN) granulosa-derived cells, cell death
      was induced by transfection of FOXO3 expression vectors. Expression of the
      proapoptotic factors Fas ligand (FASLG) and BCL2-like 11 (BCL2L11) was
      upregulated by FOXO3 in KGN cells. In conclusion, FOXO3 is expressed in porcine
      ovarian follicles and induces apoptosis in granulosa cells, suggesting that it is
      a candidate for the initiator of follicular atresia.

PMID- 21071887
TI  - Mitochondrial dysfunction influences apoptosis and autophagy in porcine
      parthenotes developing in vitro.
AB  - Mitochondria are important regulators of both apoptosis and autophagy. One of the
      triggers for mitochondrial-mediated apoptosis is the production of reactive
      oxygen species (ROS), which include hydrogen peroxide, superoxide, hydroxyl
      radical, nitric oxide and peroxynitrite. Recently, several studies have indicated
      that ROS may also be involved in the induction of autophagy. In the present
      study, we used H(2)O(2) to induce mitochondrial stress, examined apoptotic- and
      autophagic-related gene expression and observed LC3 protein (autophagosome
      presence marker) expression in porcine parthenotes developing in vitro. In
      porcine four-cell parthenotes cultured for 5 days in NCSU37 medium containing
      0.4% BSA, the developmental rate and mitochondrial distribution did not differ
      from that of the group supplemented with 100 uM H(2)O(2) but was significantly
      decreased in the group supplemented with 500 uM H(2)O(2) (P<0.05). Transmission
      electron microscopy (TEM) indicated that whereas normal shaped mitochondria were
      observed in blastocysts from the control group, abnormal mitochondria (mitophagy)
      and autophagic vacuoles were observed in blastocysts from the group that received
      500 uM H(2)O(2). Furthermore, addition of H(2)O(2) (100 uM and 500 uM) decreased
      cell numbers (P<0.05) and increased both apoptosis (P<0.05) and LC3 protein
      expression in the blastocysts. Real-time RT-PCR showed that H(2)O(2)
      significantly decreased mRNA expression of anti-apoptotic gene Bcl-xL but
      increased pro-apoptotic genes, Caspase 3 (Casp3) and Bak, and autophagy-related
      genes, microtubule-associated protein 1 light chain 3 (Map1lc3b) and lysosomal
      associated membrane protein 2 (Lamp2). However, the addition of H(2)O(2) had no
      effect on mRNA expression levels in nuclear DNA-encoded mitochondrial-related
      genes, cytochrome oxidase (Cox) 5a, Cox5b and Cox6b1, in blastocysts. These
      results suggest that H(2)O(2) leads to mitochondrial dysfunction that results in
      apoptosis and autophagy, which is possibly related to porcine early embryo
      development.

PMID- 21071888
TI  - Relationships between the first ovulation postpartum and polymorphism in genes
      relating to function of immunity, metabolism and reproduction in high-producing
      dairy cows.
AB  - The decrease in fertility and conception rates of high-producing dairy cows is
      one of the major negative impacts for today's producers. The recovery of ovarian
      activity postpartum is affected by the status of immunity, metabolism and
      reproduction and plays a critical role in subsequent fertility after parturition
      in the cow. In the present study we investigated the relationships between
      polymorphisms in genes relating to the above functions and the first postpartum
      ovulation as a marker of the recovery of ovarian function in the cow. In immune
      function related-factors, the occurrence of first postpartum ovulation within 3
      weeks in the C/C genotypes of tumor necrosis factor alpha (TNFalpha) exon (55.4%)
      and the A/G genotypes of TNFalpha promoter (55.4%) was significantly higher than
      that in T/T genotypes of TNFalpha exon (14.3%) and A/A genotypes of TNFalpha
      promoter (14.3%). Moreover, anovulatory cows with the T/T genotype of TNFalpha
      exon and the A/A genotype of TNFalpha promoter tended to have a prolonged days
      open compared with those of the other genotypes of TNFalpha polymorphisms. In
      metabolic function-related factors, ovulatory and anovulatory cows had a
      different distribution for alleles of the growth hormone receptor, but there were
      no significant differences in genotype and allele frequency of insulin-like
      growth factor-I polymorphism. No significant relationships were found between
      ovarian function after parturition and polymorphisms for reproduction-related
      genes. In conclusion, polymorphisms of TNFalpha gene both in exon and promoter
      regions have a strong association with the early first ovulation within 3 weeks
      after parturition in the high-producing dairy cow. Taken together, polymorphisms
      of TNFalpha gene could be strongly related to early first ovulation after
      parturition, thus being an effective tool of selection for improving reproductive
      performance in the high-producing dairy cow.

PMID- 21071889
TI  - 3,4-Dihydroxyflavone acts as an antioxidant and antiapoptotic agent to support
      bovine embryo development in vitro.
AB  - The effects of two antioxidants, superoxide dismutase (SOD) and the flavonoid 3,4
      dihydroxyflavone (DHF), on bovine embryo development in vitro were examined.
      Blastocyst development, total cell and inner cell mass (ICM) numbers,
      intracellular levels of reactive oxygen species (ROS), apoptotic indices and gene
      expression levels were examined before and after treatment of day 2 bovine
      embryos (>=2-4 cells) with various concentrations of 3,4-DHF or SOD for 6 days.
      Statistical analysis was performed using analysis of variance, with significance
      defined at the P<0.05 level. SOD had no significant effect on bovine embryo
      development at any tested concentration (control, 32.8%; 300 U/ml, 33.9%; 600
      U/ml, 24.2%). In contrast, 10 uM 3,4-DHF promoted higher blastocyst development
      (39.3%) than any other concentration (control, 26.7%; 1 uM, 30.3%; 50 uM, 29.5%;
      100 uM, 20.5%). Compared with 300 U/ml SOD, 10 uM 3,4-DHF resulted in
      significantly higher blastocyst development (44.2%) (control, 31.5%; SOD 300
      U/ml, 33.6%). Treatment with 3,4-DHF increased the ICM cell number and reduced
      intracellular ROS production and apoptotic cell numbers. When O(2) tension was
      decreased from 20% (high tension) to 5% (low tension), embryo development rates
      were doubled regardless of 3,4-DHF treatment. Under high O(2) tension, 10 uM 3,4
      DHF treatment may render bovine embryo development similar to a low O(2) tension
      environment. The best blastocyst development was obtained under low O(2) tension
      plus 10 uM 3,4-DHF treatment. The relative expression levels of antioxidant
      (MnSOD), antiapoptotic (Survivin, Bax inhibitor) and growth-related genes (IFN
      tau, Glut-5) were significantly increased after 3,4-DHF treatment, while the
      expression levels of oxidant (Sox) and apoptotic genes (Caspase-3 and Bax) were
      reduced. These results suggest that 3,4-DHF may promote the in vitro development
      of bovine embryos through its antioxidant and antiapoptotic effects.

PMID- 21071890
TI  - [Histopathological diagnosis of precancerous lesions of the gastrointestinal
      tracts].

PMID- 21071891
TI  - [Precancer lesion of the esophagus --studies on endoscopic findings and clinical
      management].

PMID- 21071892
TI  - [Precancerous lesions of the stomach].

PMID- 21071893
TI  - [Endoscopic diagnosis and treatment for colorectal adenomas].

PMID- 21071894
TI  - [A case of giant esophageal leiomyoma successfully resected by endoscopic
      submucosal dissection followed by retrieval via laparotomy].
AB  - A 30-year-old woman with chest discomfort at swallowing and occasional vomiting
      was referred to our department with a diagnosis of esophageal submucosal tumor.
      CT visualized a mass 70 mm in diameter in the middle esophagus.
      Esophagogastroduodenoscopy revealed a pedunculated submucosal tumor, and
      endoscopic resection was considered. As the size of the tumor was so large,
      retrieval of the resected specimen via the stomach following incision, laparotomy
      was planned. En bloc resection by endoscopic submucosal dissection with a Hook
      knife was performed. Retrieval of the resected specimen was carried out as
      planned. The specimen, which was 53*48*43mm in size with a distinct margin, was
      diagnosed as leiomyoma derived from the muscularis mucosae histologically. Her
      postprocedural course was uneventful. Endoscopic resection can be chosen when an
      esophageal submucosal tumor is pedunculated with abundant mobility, making it
      possible to avoid invasive surgery.

PMID- 21071895
TI  - [Three cases of squamous cell carcinoma of the esophagus who underwent argon
      plasma coagulation as salvage treatment for locoregional failure or remnant tumor
      after chemoradiotherapy].
AB  - We report 3 cases of locoregional failure or remnant esophageal squamous cell
      carcinoma after chemoradiotherapy that were successfully treated by argon plasma
      coagulation (APC) as a salvage treatment. Ablation was performed using argon
      plasma coagulation APC300 (ERBE). A power setting of 60W and an argon gas flow of
      1.8L/min was used. APC is able to be repeated multiply without adverse reaction,
      and is an effective treatment to control the tumor growth.

PMID- 21071896
TI  - [A case of postoperative recurrent gastric cancer resembling esophageal achalasia
      diagnosed by endoscopic ultrasound-guided fine-needle aspiration].
AB  - A 74 year-old man underwent subtotal gastrectomy for advanced gastric cancer in
      2000. The histological type of the cancer was signet-ring cell carcinoma, and the
      clinical stage was stage II (T2, N1, M0). In June 2008 the patient was referred
      to our hospital complaining of dysphagia. Esophageal endoscopy revealed a
      circular stenosis with covered with normal mucosa between the lower esophagus and
      the esophago-gastric junction. Histologically, samples obtained by endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA) revealed signet-ring cell
      carcinoma. Our experience suggests that EUS-FNA was useful for the histological
      diagnosis of recurrence of gastric cancer.

PMID- 21071897
TI  - [A case of giant heterotopic Brunner's gland adenoma prolapsing into the
      duodenum].
AB  - A 81-year-old woman admitted with general fatigue was found to have a giant polyp
      in the gastric antrum by endoscopy. The polyp prolapsed into the duodenum through
      the pylorus. Angiographic examination of the abdomen revealed the polyp to be
      about 90*35 mm in size. Laparotomy was performed. It was finally diagnosed as
      heterotopic Brunner's gland adenoma which had a stalk on the antrum of the
      stomach. Heterotopic Brunner's gland adenoma is rare. Only 3 cases including the
      present case have been reported in Japan.

PMID- 21071898
TI  - [A case of jejunal adenocarcinoma with serum DUPAN-2 elevation].
AB  - A 50-year-old woman was admitted to our hospital because of abdominal pain and
      vomiting. Ileus with ulcerated jejunal tumor was diagnosed and biopsy revealed
      adenocarcinoma. Because her serum level of DUPAN-2 was high, she was examined by
      PET scan, which revealed that she had a left ovarian mass in addition to the
      jejunal tumor. Surgical resection was performed: both tumors were adenocarcinoma,
      but the ovarian tumor was considered to be metastatic clinically and
      histologically. Immunostaining for DUPAN-2 was positive in the both tumors. The
      serum level of DUPAN-2 returned to normal after the surgery, and has been within
      normal limits for about 3 years without any additional therapy. This case shows a
      possible relation between small bowel adenocarcinoma and DUPAN-2.

PMID- 21071899
TI  - [A case of portal vein thrombosis complicating acute cholangitis treated
      successfully with danaparoid sodium].
AB  - An 81-year-old woman was referred to our hospital with a diagnosis of acute
      cholangitis. Endoscopic retrograde cholangiography revealed a common bile duct
      (CBD) stone. In addition, CT showed thrombus of the right portal vein. Endoscopic
      sphincterotomy was performed to remove the CBD stone. Thrombosis was treated
      successfully with danaparoid sodium. It was speculated that the treatment of the
      acute cholangitis induced thrombolysis by the auto-fibrinolysis system and
      danaparoid sodium prevented the development of thrombus formation in this case.

PMID- 21071900
TI  - [A case of well differentiated mucinous carcinoma of the gallbladder].
AB  - We report a case of well differentiated mucinous carcinoma of the gallbladder. An
      80-year-old man was admitted to our hospital because of fever and CT showed a
      mass in the fundus of the gallbladder and choledocholithiasis. Endoscopic removal
      of the common bile duct stones was done. Abdominal ultrasonography and CT showed
      a 4 cm mass in the fundus of the gallbladder. Based on a diagnosis of
      adenomyomatosis or mucinous carcinoma of the gallbladder, a laparotomy revealed a
      white mass in the fundus of gallbladder. Intra-operative pathological diagnosis
      of lymph node of cystic duct was mucinous carcinoma. Therefore, we conducted
      partial resection of the liver with D1 lymph node dissection. Pathological
      diagnosis confirmed well differentiated mucinous carcinoma of the gallbladder.
      His postoperative course was uneventful, and he is doing well without recurrence.

PMID- 21071901
TI  - [Mucinous cystic neoplasm of the pancreas associated with pregnancy: report of
      two cases].
AB  - Pancreatic neoplasms during pregnancy are rare. We describe two cases of mucinous
      cystic neoplasm (MCN) associated with pregnancy. A 34-year-old woman in the 26th
      week of pregnancy was given a diagnosis of MCN measuring 19 cm in diameter. We
      decided to resect it post partum in consideration of the risk of abortion. She
      had a healthy infant in the 40th week of pregnancy and three months later, distal
      pancreatectomy was performed. Pathological analysis revealed a mucinous
      cystadenoma of the pancreas. The second case was a 36-year-old woman. She was
      given a diagnosis of MCN, measuring 16 cm in diameter, post partum and distal
      pancreatectomy was performed. Pathologically, the tumor was an invasive mucinous
      cystadenocarcinoma of the pancreas. In this report, we did an extensive
      literature review and discussed the management of MCN during pregnancy with
      special reference to the timing of the operation and the relationship between
      tumor growth and sex hormones.

PMID- 21071902
TI  - [Stable isotope ratio analyses of light elements and their application to
      verifying geographical origin of foods].

PMID- 21071903
TI  - [Absolute quantitation of quercetin and the glycosides in natural food additives
      by quantitative NMR].
AB  - We are developing a simple absolute quantitation method for organic compounds, by
      means of quantitative nuclear magnetic resonance (qNMR), with traceability to the
      International System of Units (SI units). The qNMR method was applied to the
      absolute quantitation of rutin, isoquercitrin and quercetin in natural food
      additives, rutin (extract), enzymatically decomposed rutin extract and quercetin,
      and those compounds as commercial reagents. In this study, 1,4-bis
      (trimethylsilyl)benzene-d(4) (1,4-BTMSB-d(4)) whose purity was precisely
      evaluated on the basis of metrology, was newly used as a qNMR reference material,
      to be added to the sample solution as an internal standard. The contents of
      quercetin and quercetin glycosides were calculated from the ratio of the signal
      intensities of each aromatic proton at the 2' position of the three compounds
      (these are observed at different chemical shifts) to the eighteen protons of the
      six methyl groups on 1,4-BTMSB-d(4) used as a qNMR reference material. Rapid and
      simple qNMR method with only one step process was carried by using 1,4-BTMSB
      d(4). It was demonstrated that the purities of rutin, isoquercitrin and quercetin
      can be separately determined by qNMR without the need for a separation process or
      reference materials for all the target compounds.

PMID- 21071904
TI  - Determination of dithiocarbamates and milneb residues in foods by gas
      chromatography-mass spectrometry.
AB  - A highly sensitive gas chromatographic-mass spectrometric (GC-MS) method was
      developed for dithiocarbamates (DTCs) and milneb in foods. DTCs and milneb were
      extracted from foods with cysteine-EDTA solution as sodium salts, and methylated
      with methyl iodide. Methyl derivatives of DTCs and milneb were cleaned up on a
      neutral alumina mini column and determined by GC-MS. The mean recoveries of DTCs
      and milneb were in the range of 72-120%, except for methiram. The quantification
      limits were 0.01 mg/kg (as CS(2)) in foods except tea (0.1 mg/kg as CS(2)). The
      developed method was applied to 10 compounds (4 dimethyldithiocarbamates, 3
      ethylenebisdithiocarbamates, polycarbamates, propineb and milneb).

PMID- 21071905
TI  - [Determination of substances in polylactic acid products for food-contact use and
      mutagenicity of their migration solutions].
AB  - Specification tests defined in the Japanese Food Sanitation Law were conducted on
      7 polylactic acid food-contact products. Moreover, the content and migration of
      other compounds were examined by means of ICP-AES, GC/MS and mutagenicity tests.
      All products met their specifications, and migration levels of heavy metals were
      negligible. No notable peak was observed in GC/MS analysis. Moreover, all
      products gave negative results in both rec-assay and the umu-test. An increase in
      the beta-galactosidase activity in the umu-test observed with the migration
      solution of soup bowl was due not to polylactic acid, but to the polyurethane
      coating.

PMID- 21071906
TI  - [Migration of monomers and primary aromatic amines from nylon products].
AB  - Migration of 2 kinds of monomer and 21 kinds of primary aromatic amines (PAAs)
      from 21 kinds of nylon products such as turners, ladles and wrap film were
      determined. Samples were classified as regards materials by mean of pyrolysis
      GC/MS. One sample was classified as nylon 6, 15 samples as nylon 66 and three
      samples as nylon 6/66 copolymers, while two samples were laminate of nylon 6 with
      polyethylene or polypropylene. All of the nylon 66 samples contained a small
      amount of epsilon-caprolactam (CPL), which is the nylon 6 monomer. Migration
      levels of monomers and PAAs at 60 degrees C for 30 min into 20% ethanol were
      measured by LC/MS/MS. CPL was detected at the level of 0.015-38 ug/mL from all
      samples, excluding one wrap film sample, and 1,6-hexamethylenediamine was
      detected at the level of 0.002-0.013 ug/mL from all nylon 66 samples and one
      nylon 6/66 sample. In addition, 0.006-4.3 ug/mL of 4,4'-diaminodiphenylmethane
      from three samples, 0.032-0.23 ug/mL of aniline from four samples, 0.001 ug/mL of
      4-chloroaniline from two samples, and 0.002 ug/mL of 2-toluidine and 0.066 mg/mL
      of 1-naphthylamine from one sample each were detected. The migration levels at 95
      or 121 degrees C were about 3 and 10 times the 60 degrees C levels, respectively.

PMID- 21071907
TI  - [Detection of norovirus RNA in bivalve molluscs by using bacteria-culture
      employed method (A3T method)].
AB  - Norovirus (NV) RNA has rarely been detected in foods despite the use of highly
      sensitive methods such as RT-PCR and real-time RT-PCR. In the modified method
      (A3T method) reported previously, a bacterial culture process was introduced into
      the standard protocol for NV detection to remove some inhibitor(s) present in
      food ingredients. To confirm the efficiency of the A3T method and to examine NV
      contamination in bivalve molluscs, we tried to detect NV RNA in bivalve molluscs
      on the market and in oyster samples associated with foodborne outbreaks by using
      the standard method and the A3T method. NV RNAs were detected in 20 samples
      (18.0%) of 111 bivalve molluscs, including oysters, on the market by use of the
      A3T method, while only one sample (0.9%) was positive according to the standard
      method. NV RNA was also detected in 10 of 35 oyster samples related to foodborne
      outbreaks by the A3T method. Those results show that the A3T method is suitable
      for the detection of NV in bivalve molluscs in general laboratories.

PMID- 21071908
TI  - Establishment and evaluation of event-specific quantitative PCR method for
      genetically modified soybean MON89788.
AB  - A novel real-time PCR-based analytical method was established for the event
      specific quantification of a GM soybean event MON89788. The conversion factor
      (C(f)) which is required to calculate the GMO amount was experimentally
      determined. The quantitative method was evaluated by a single-laboratory analysis
      and a blind test in a multi-laboratory trial. The limit of quantitation for the
      method was estimated to be 0.1% or lower. The trueness and precision were
      evaluated as the bias and reproducibility of the relative standard deviation
      (RSD(R)), and the determined bias and RSD(R) values for the method were both less
      than 20%. These results suggest that the established method would be suitable for
      practical detection and quantification of MON89788.

PMID- 21071909
TI  - [Extraction and purification method of rice DNA from rice powder containing
      Konjak flour].
AB  - Rice powder containing Konjak flour made with tuberous roots of Amorphophallus
      konjac is imported as a rice-processed product from China to Japan. An improved
      DNA purification method for the polymerase chain reaction (PCR) analysis of rice
      in such products is necessary, since Konjak flour constituents absorb the DNA
      purification buffer to form a gel, and cause problems in the subsequent
      purification steps. Here, we present a simple preparative system for isolation of
      the rice and a purification method of the rice DNA from the product. The purified
      DNA was confirmed to be a good template for both PCR and real-time PCR.

PMID- 21071910
TI  - [Preparation of samples for proficiency testing of pesticide residue analysis in
      processed foods].
AB  - To conduct proficiency testing for the analysis of pesticide residues in
      processed foods, fortified samples of retort curry and pancake were examined. In
      the case of retort curry, heating and mixing were necessary at the time of
      preparation to provide a homogenous analytical sample. A mixture of 4 carbamates
      and 11 organophosphorus pesticides was spiked and 14 of them showed consistent
      results in the samples. In the case of pancake, 10 kinds of pesticides were added
      to the pastry. The prepared pastry was them cooked. The relative concentrations
      of most of the pesticides in the pancake were not affected and all the pesticides
      showed consistent results in the samples. These results showed that the two
      tested samples were suitable for proficiency testing.

PMID- 21071911
TI  - [Correlation of fat content and dioxins, total mercury and methyl mercury levels
      in tuna].
AB  - In this study, we analyzed the concentrations of mercury and dioxins in tuna with
      various fat contents (akami; the leaner meat, Chutoro; the belly area of the tuna
      along the side of the fish between the akami and the otoro. Otoro; the fattiest
      portion of the tuna) in wild and farmed bluefin tuna and farmed southern bluefin
      tuna. In the three kinds of tuna, average dioxins concentrations in Akami,
      chutoro and otoro were 1.7, 4.7 and 9.6 pg TEQ/g, respectively. The dioxins
      concentration in all three regions of tuna was in direct proportion to the fat
      content. In the farmed bluefin tuna, the dioxins concentration was almost the
      same as that of the wild tuna, but differed from that of the farmed southern
      bluefin tuna. Average total mercury concentration based on wet weight in akami
      was 0.42 ug/g, being higher than the values of 0.36 ug/g of chutoro and 0.31 ug/g
      of otoro, and in inverse proportion to the fat content. In all three regions, the
      total mercury concentration of the wild bluefin tuna was equal to that of the
      farmed tuna. The total mercury concentration in the latter was two to three times
      higher than that of the farmed southern bluefin tuna. If the Japanese intake is
      one fin of tuna (80 g) a day, the daily intake levels of dioxins and methyl
      mercury can be estimated as 0.48-37 pg TEQ/kg bw and 0.21-0.90 ug/kg bw,
      respectively.

PMID- 21071912
TI  - [Identification methods of terpenoid gum bases using TLC and GC/MS].
AB  - Simple chromatographic methods were applied to terpenoid resins used as gum
      bases. Five triterpenoid resins, mastic, dammar resin, olibanum, benzoin gum and
      elemi resin, and two diterpenoid resins, rosin and copal resin, were separated
      with normal-phase TLC. Characteristic patterns were observed for all resins.
      Different samples of the same resin gave identical patterns. The TLC method is a
      candidate for a simple identification test for terpenoids resins. Samples were
      then methyl-esterified and analyzed with GC/MS. All resins exhibited
      characteristic chromatograms for total ion current. Major constituents of all
      resins were detected. Unique constituents that can be used as indicators were
      found in every resin. Therefore, GC/MS of methyl-esterified terpenoid resins is a
      valuable identification method.

PMID- 21071913
TI  - Clinical decision making in dermatology: observation of consultations and the
      patients' perspectives.
AB  - BACKGROUND: Clinical decision making is a complex process and might be influenced
      by a wide range of clinical and non-clinical factors. Little is known about this
      process in dermatology. AIMS: The aim of this study was to explore the different
      types of management decisions made in dermatology and to identify factors
      influencing those decisions from observation of consultations and interviews with
      the patients. METHODS: 61 patient consultations were observed by a physician with
      experience in dermatology. The patients were interviewed immediately after each
      consultation. Consultations and interviews were audio recorded, transcribed and
      their content analysed using thematic content analysis. RESULTS: The most common
      management decisions made during the consultations included: follow-up, carrying
      out laboratory investigation, starting new topical treatment, renewal of systemic
      treatment, renewal of topical treatment, discharging patients and starting new
      systemic treatment. Common influences on those decisions included: clinical
      factors such as ineffectiveness of previous therapy, adherence to prescribing
      guidelines, side-effects of medications, previous experience with the treatment,
      deterioration or improvement in the skin condition, and chronicity of skin
      condition. Non-clinical factors included: patient's quality of life, patient's
      friends or relatives, patient's time commitment, travel or transportation
      difficulties, treatment-related costs, availability of consultant, and
      availability of treatment. CONCLUSION: The study has shown that patients are
      aware that management decisions in dermatology are influenced by a wide range of
      clinical and non-clinical factors. Education programmes should be developed to
      improve the quality of decision making.

PMID- 21071914
TI  - Systemic inflammatory response and survival in patients with localised prostate
      cancer: 10-year follow-up.

PMID- 21071916
TI  - Characterization of dental pulp stem cells from impacted third molars cultured in
      low serum-containing medium.
AB  - We isolated and expanded stem cells from dental pulp from extracted third molars
      using an innovative culture method consisting of low serum-containing medium
      supplemented with epidermal growth factor and platelet-derived growth factor BB.
      We evaluated the differentiation potential of these cells when they were growing
      either adherently or as micromass/spheroid cultures in various media.
      Undifferentiated and differentiated cells were analyzed by flow cytometry,
      immunocytochemistry and immunoblotting. The flow cytometry results showed that
      the dental pulp stem cells (DPSCs) were positive for mesenchymal stromal cell
      markers, but negative for hematopoietic markers. Immunocytochemical and/or
      immunoblotting analyses revealed the expression of numerous stem cell markers,
      including nanog, Sox2, nestin, Musashi-1 and nucleostemin, whereas they were
      negative for markers associated with differentiated neural, vascular and hepatic
      cells. Surprisingly, the cells were only slightly positive for alpha-smooth
      muscle actin, and a heterogeneous expression of CD146 was observed. When cultured
      in osteogenic media, they expressed osteonectin, osteopontin and procollagen I,
      and in micromass cultures, they produced collagen I. DPSCs cultured in TGF
      beta1/3-supplemented media produced extracellular matrix typical of cartilaginous
      tissue. The addition of vascular endothelial growth factor to serum-free media
      resulted in the expression of endothelial markers. Interestingly, when cultured
      in neurogenic media, DPSCs exhibited de novo or upregulated markers of
      undifferentiated and differentiated neural cells. Collectively, our data show
      that DPSCs are self-renewing and able to express markers of bone, cartilage,
      vascular and neural tissues, suggesting their multipotential capacity. Their easy
      accessibility makes these cells a suitable source of somatic stem cells for
      tissue engineering.

PMID- 21071917
TI  - Halothane-anesthetized rabbit: a new experimental model to test the effects of
      besipirdine and duloxetine on lower urinary tract function.
AB  - INTRODUCTION: The effects of besipirdine and its main metabolite, HP-748, as well
      as duloxetine and tomoxetine in the lower urinary tract (LUT) were studied using
      in vitro and in vivo techniques. MATERIALS AND METHODS: For in vivo studies,
      besipirdine or duloxetine effects on cystometric parameters and striated
      sphincter electromyographic (SS-EMG) activity were investigated. On the isolated
      urethra, norepinephrine (NE) concentration-response curves (CRC) were performed
      in the presence of besipirdine, duloxetine or tomoxetine. Moreover, CRC to HP-748
      were constructed in the absence or presence of prazosin. Potency (pEC(50)) and
      maximal responses (E(max)) were determined. RESULTS: Besipirdine at 1, 3 and 5
      mg/kg intravenously (i.v.) induced a significant increase in SS-EMG activity
      (250, 273 and 241%, respectively), bladder capacity (172, 197, and 235%,
      respectively), intercontraction interval (ICI; 208, 242, and 400%, respectively),
      and residual volume (181, 191, and 236%, respectively). Duloxetine at 2 mg/kg
      i.v. increased significantly SS-EMG activity (219%), micturition volume (222%),
      and ICI (205%). In the isolated urethra, besipirdine, tomoxetine and duloxetine
      significantly displaced to the left the NE CRC. In addition, HP-748 induced
      contraction of the isolated urethra with a pEC(50) of 5.89 and an E(max) of 37%.
      CONCLUSIONS: These data support the potential of besipirdine as a new drug for
      LUT dysfunctions such as stress and mixed urinary incontinence.

PMID- 21071918
TI  - Delayed detection of injury to an ectopic ureter of a duplicated collecting
      system following laparoscopic radical prostatectomy for early organ-confined
      prostate cancer.
AB  - In the era of early detection of organ-confined prostate cancer, guidelines
      support the fact that many patients will not need an aggressive staging work-up,
      to avoid unnecessary investigations. This strategy may lead to serious
      repercussions in rare incidences. We present a rare case of urinary extravasation
      following laparoscopic radical prostatectomy caused by injury of the upper pole
      ectopic ureter of an undetected duplex system on 1 side, an injury which is the
      first of its kind in laparoscopic urology.

PMID- 21071915
TI  - Molecular and physiological responses to juvenile traumatic brain injury: focus
      on growth and metabolism.
AB  - Traumatic brain injury (TBI), one of the most frequent causes of neurologic and
      neurobehavioral morbidity in the pediatric population, can result in lifelong
      challenges not only for patients, but also for their families. Survivors of a
      brain injury experienced during childhood - when the brain is undergoing a period
      of rapid development - frequently experience unique challenges as the
      consequences of their injuries are overlaid on normal developmental changes.
      Experimental studies have significantly advanced our understanding of the
      mechanisms and underlying molecular underpinnings of the injury response and
      recovery process following a TBI in the developing brain. In this paper, normal
      and TBI-related alterations in growth, development and metabolism are
      comprehensively reviewed in the postweanling/juvenile age range in the rat
      (postnatal days 21-60). As part of this review, TBI-related changes in gene
      expression are presented, with a focus on the injury-induced alterations related
      to cerebral growth and metabolism, and discussed in the context of existing
      literature related to physiological and behavioral responses to experimental TBI.
      Increasing evidence from the existing literature and from our own gene microarray
      data indicates that molecular responses related to growth, development and
      metabolism may play a particularly important role in the injury response and the
      recovery trajectory following developmental TBI. While gene expression analysis
      shows many of these changes occur at the level of transcription, a comprehensive
      review of other studies suggests that the control of metabolic substrates may
      preferentially be regulated through changes in transporters and enzymatic
      activity. The interrelation between cellular metabolism and activity-dependent
      neuroplasticity shows great promise as an area for future study for an optimal
      translation of experimental data to clinical TBI, with the ultimate goal of
      guiding therapeutic interventions.

PMID- 21071919
TI  - Are bacterial growth and/or chemotaxis increased by filler injections?
      Implications for the pathogenesis and treatment of filler-related granulomas.
AB  - BACKGROUND: As microbial agents have been associated with late adverse effects
      related to fillers antibiotic treatment has been envisaged. OBJECTIVE: To
      determine whether biomaterials favor bacterial growth and/or attract bacteria.
      METHODS: Hyaluronic acid, semi-permanent fillers, such as calcium
      hydroxylapatite, and permanent fillers, such as polyalkylimide/polyacrylamide,
      were used. Experiments were performed with Escherichia coli, strain HVH-U47.
      Bacteria were transferred to Sven-Gard agar to test mobility. Striae of this
      bacterial strain with a MacFarland 1 turbulence pattern were seeded from a spot
      of inoculated biomaterial using Muller-Hinton medium. The chemoattractive
      properties of the biomaterials were analyzed 10 days after inoculation. Bacterial
      growth over the biomaterial and in-depth growth were assessed as well. RESULTS:
      Semi-permanent fillers did not stimulate bacterial growth but they allowed
      bacterial colonization over the filler. Permanent acrylic compounds neither
      presented chemoattractant properties nor showed bacterial growth over the
      biomaterial. Similar results were obtained when performing in-depth cultures.
      CONCLUSIONS: Permanent and semi-permanent fillers did not facilitate bacterial
      growth when flagellated E. coli HVH-U47 was used. Our results do not argue in
      favor of antibiotics as the mainstay of therapy in late granulomas related to
      permanent fillers. In the case of resorbable/semi-permanent fillers, more studies
      are needed before recommending antibiotic therapy.

PMID- 21071920
TI  - The rhodoid nevus: a proposed term for a so far unnamed capillary malformation.

PMID- 21071921
TI  - EpiDex(r) Swiss field trial 2004-2008.
AB  - BACKGROUND: Approximately 20% of leg ulcers remain unresponsive to the best
      conservative standard of care. So far, these patients could either receive
      conventional skin grafts or had to accept their intractable wound. Skin
      substitutes from cell culture may represent a promising alternative to heal a
      major part of these patients on a non-surgical, potentially more cost-effective
      basis. OBJECTIVE: To systematically evaluate the first 68 patients treated in
      Switzerland (Swiss EpiDex(r) field trial 2004-2008). METHODS: Retrospective study
      on EpiDex treatment of a complete consecutive series of 68 patients with chronic
      wounds (66 chronic leg ulcers, 2 sores) unresponsive to best conservative
      standard of care. The primary end point was complete wound closure within 9
      months after transplantation, the secondary end points change of wound surface
      area, pain reduction and overall judgement by the patient. Adverse effects were
      infection, dermatitis and others. Calculation of treatment costs was made.
      RESULTS: By the end of the study, 50/68 (74%) of patients had their wound
      completely healed [venous 29/37 (78%); mixed 7/9 (78%); others 14/22 (64%)];
      10/68 (15%) had the wound surface area reduced by >50%, and 8/68 (12%) did not
      respond to the EpiDex treatment. Wound pain disappeared completely in 78% and
      partially in 13%. Fifteen patients (22%) received antibiotics for wound
      infection, and 2 (3%) developed dermatitis (not related to the local therapy).
      Average treatment costs for venous ulcers amounted to EUR 5,357, compared to EUR
      5,722-8,622 reimbursed according to the German DRG system (2010) for an in
      patient skin graft. CONCLUSION: EpiDex may effectively heal up to three quarters
      of recalcitrant chronic leg ulcers. Thus, it represents an intermediate step to
      avoid costly in-patient split-skin mesh graft treatments. Patients remain
      mobilized, and a donor site is avoided. Large wound size or a necrotic wound bed
      limit the use of EpiDex. Otherwise, it offers the opportunity to avoid
      conventional skin grafts in a significant number of chronic leg ulcer patients.

PMID- 21071922
TI  - Evaluation of two real-time multiplex PCR screening assays detecting fetal RHD in
      plasma from RhD negative women to ascertain the requirement for antenatal RhD
      prophylaxis.
AB  - OBJECTIVE: To evaluate two different multiplex real-time PCR assays detecting
      fetal RHD for screening of RhD negative women in relation to antenatal RhD
      prophylaxis. METHODS: We designed a duplex assay for the detection of RHD exon 7
      and 10 and a triplex assay for the detection of RHD exon 7, 10 and 5. We used the
      same fluorescent dye for the exon 7 and 10 probes to increase sensitivity; exon 5
      was VIC labeled. We evaluated possible inhibition of DNA amplification with
      dilution experiments. We then tested the two multiplex assays with DNA extracted
      from 97 plasma samples from 38 RhD negative women in gestational weeks 6-37.
      RESULTS: Dilution experiments revealed no inhibition of amplification in the
      multiplex assays. For plasma samples, the duplex assay was significantly more
      sensitive than the triplex assay (p < 0.0001). For the duplex assay (exon 7/10),
      accuracy was 99.0%. For the triplex assay (exon 7/10), accuracy was 94.2%.
      Detection of exon 5 was less reliable. CONCLUSION: The duplex assay using exon
      7/10 was the most reliable for prenatal prediction of fetal RhD type as a
      candidate assay for screening of RhD negative women in relation to antenatal RhD
      prophylaxis. The triplex assay needs further optimization.

PMID- 21071924
TI  - More on speckled lentiginous nevus syndrome.

PMID- 21071923
TI  - Curcumin facilitates fibrinolysis and cellular migration during wound healing by
      modulating urokinase plasminogen activator expression.
AB  - Urokinase plasminogen activator (uPA) plays a vital role in the early phases of
      wound healing by aiding fibrin dissolution and promoting the migration,
      proliferation, and adhesion of various cells to the wound bed. The efficacy of
      botanicals in healing wounds is an area of active research. Among these,
      curcumin, a yellow pigment abundant in turmeric rhizome, has been the center of
      extensive studies. This study focused on the effect of curcumin on uPA expression
      and its consequence on fibrin dissolution and cellular migration. Treatment of
      human fibroblast cells with curcumin caused an upregulation of uPA mRNA and
      protein. Activation of JNK and p38 MAPK signal pathways was necessary for the
      upregulation of uPA. Curcumin treatment resulted in an increase in fibrinolytic
      activity and cell migration towards the wound area. The involvement of uPA in
      fibrinolysis and cell migration was confirmed by zymography and siRNA studies,
      respectively.

PMID- 21071925
TI  - Y-chromosome disomy and trisomy in scarabaeid and cerambycid beetles.
AB  - In a series of about 500 specimens, including 420 males, of karyotyped Polyphaga
      beetles, 5 males with chromosome Y aneuploidy were detected. One male of each
      Dicronorrhina derbyana oberthuri (Scarabaeidae), Agapanthia violacea and Morimus
      funereus (Cerambycidae) were XYY, and 2 probably related and sterile males of
      Marmylida marginella (Scarabaeidae) were XYYY. These and literature data suggest
      that Y chromosome aneuploidies are much more frequent in polyphagan beetles than
      any other group of animals with an XY/XX sex determinism. The origin of this
      particularity probably lies in the unique mode of sex chromosome association at
      meiosis I: it is not synaptic but realized through nucleolar proteins forming the
      well-known parachute-like structure (Xy(p)). This has 2 possible consequences.
      The first one is the regular association of several sex chromosomes at metaphase
      I and segregation at anaphase I. It allows, for instance, XYY (Xyy(p)) males to
      procreate XYY sons. The second consequence is the occasional remain of nucleolar
      proteins embedding sex chromosomes in spermatocytes II. We propose that it could
      impede the correct segregation of Y chromatids after centromere split at anaphase
      II, and contribute to form YY gametes by XY males and YYY gametes by XYY males.
      The tendency for increasing the number of Ys would not be strongly limited at the
      XY level, but only at the XYY level by male infertility at higher Y ploidies.

PMID- 21071926
TI  - Is prostate-specific antigen surveillance necessary in men with benign prostate
      pathology following radical cystoprostatectomy for bladder cancer?
AB  - BACKGROUND: Radical cystoprostatectomy (RCP) remains the gold standard for the
      treatment of muscle-invasive bladder cancer. There are limited data regarding the
      clinical impact and detection of PSA following complete prostatectomy or the need
      to monitor serum PSA in patients with benign prostate pathology at time of RCP.
      The purpose of our study was to analyze the postoperative PSA characteristics of
      men without prostate cancer who underwent a RCP for bladder cancer. METHODS: The
      demographic, clinical and pathologic data were reviewed on 138 men who underwent
      RCP for bladder cancer from 1994 to 2008. Patients with known or incidentally
      discovered prostate cancer on final pathology were excluded from this study, and
      postoperative serum PSA values were reviewed in the remaining men. RESULTS: The
      median age of the study population was 64 years (range 40-84). At a mean follow
      up of 40.7 months, 137 (99.3%) of patients had an undetectable serum PSA. The one
      (0.7%) case in which serum PSA was not undetectable underwent an apex-sparing
      prostatectomy at the time of cystectomy. CONCLUSIONS: Serum PSA should remain
      undetectable for men with benign prostate pathology undergoing complete
      prostatectomy at the time of RCP. Elevated serum PSA following complete RCP in
      men with bladder cancer and pathologically confirmed benign prostate findings is
      rare. If the serum PSA is undetectable 3 months after RCP with benign prostate
      pathology, there is no need for continued PSA monitoring. These data support the
      notion that potential nonprostatic sources of PSA are clinically insignificant
      following complete removal of the prostate.

PMID- 21071927
TI  - Health system implications of direct-to-consumer personal genome testing.
AB  - Direct-to-consumer personal genome testing is now widely available to consumers.
      Proponents argue that knowledge is power but critics worry about consumer safety
      and potential harms resulting from misinterpretation of test information. In this
      article, we consider the health system implications of direct-to-consumer
      personal genome testing, focusing on issues of accountability, both corporate and
      professional.

PMID- 21071928
TI  - HJV hemochromatosis, iron overload, and hypogonadism in a Brazilian man:
      treatment with phlebotomy and deferasirox.

PMID- 21071929
TI  - Acute myelogenous leukemia patients are at low risk for invasive fungal
      infections after high-dose cytarabine consolidations and thus do not require
      prophylaxis.
AB  - We evaluated the frequency of invasive fungal infections (IFI), the frequency of
      empirical antifungal use (EAFU), and the efficacy of fluconazole prophylaxis on
      IFI and EAFU after high-dose cytarabine (HiDAC) consolidations. Twenty-seven
      acute myelogenous leukemia patients in their first complete remission received 76
      cycles of HiDAC (median cycle: n = 3). Fluconazole prophylaxis was administered
      following 44 cycles (fluconazole group) and not given in 32 cycles (control
      group). IFI (2 episodes) + EAFU (11 episodes) was observed in 13 of 76 cycles
      (17%); there was no difference between the fluconazole group and the control
      group (p = 0.469). Neutropenia duration was <13 days in 89% of the 76 cycles and
      was similar in the fluconazole and control groups (p = 0.845). Neutropenic fever
      was observed in 34 of the 76 cycles (45%) and was similar in the fluconazole
      group and the control group (p = 0.43). Although HiDAC cycle 1 was associated
      with a shorter neutropenia duration, there was no association between HiDAC cycle
      numbers and neutropenic fever or IFI + EAFU. HiDAC consolidations resulted in a
      high rate of neutropenic fever, the lack of an appreciable benefit from EAFU, and
      rare IFI. Most likely because of the low incidence of IFI, use of fluconazole or
      another antifungal is not warranted in this setting.

PMID- 21071930
TI  - High factor VIII activity, high plasminogen activator inhibitor 1 antigen levels
      and low factor XII activity contribute to a thrombophilic tendency in elderly
      venous thromboembolism patients.

PMID- 21071931
TI  - In vivo evaluation method of the effect of nattokinase on carrageenan-induced
      tail thrombosis in a rat model.
AB  - Thrombosis is characterized by congenital and acquired procatarxis. Nattokinase
      inhibits thrombus formation in vitro. However, in vivo evaluation of the
      therapeutic efficacy of nattokinase against thrombosis remains to be conducted.
      Subcutaneous nattokinase injections of 1 or 2 mg/ml were administered to the
      tails of rats. Subsequently, kappa-carrageenan was intravenously administered to
      the tails at 12 h after nattokinase injections. The mean length of the infarcted
      regions in the tails of rats was significantly shorter in rats administered 2
      mg/ml of nattokinase than those in control rats. Nattokinase exhibited
      significant prophylactic antithrombotic effects. Previously, the in vitro
      efficacy of nattokinase against thrombosis had been reported; now our study has
      revealed the in vivo efficacy of nattokinase against thrombosis.

PMID- 21071932
TI  - Spontaneous regression of chronic myeloid leukemia during pregnancy.

PMID- 21071933
TI  - Glycated hemoglobin predicts mortality in nondiabetic patients receiving chronic
      peritoneal dialysis.
AB  - BACKGROUND: patients with chronic peritoneal dialysis (CPD) use glucose-based
      dialysate to maintain their life; however, whether the glycemic status influences
      outcome of these patients without diabetes remains unknown. METHODS: we conducted
      a cross-sectional and 18-month prospective study, and 269 nondiabetic patients
      with CPD were enrolled in a medical center. Glycated hemoglobin (HbA1c) levels
      were measured at baseline and categorized in tertiles of HbA1c: high (>5.4%),
      middle (5.1-5.4%) and low normal (<5.1%). Mortality and cause of death were
      recorded for longitudinal analyses. RESULTS: the study results showed high HbA1c
      group patients had a trend of being older and having higher body mass index (BMI)
      than other group patients. Stepwise multiple linear regression analysis showed
      HbA1c was positively related to age, BMI and the peritoneal solute transport
      rate. After 18 months of follow-up, Cox multivariate analysis showed that HbA1c
      (HR: 4.114; 95% CI: 1.426-11.872; p = 0.009) was the significant risk factor for
      all-cause mortality after relating variables were adjusted. Moreover, high HbA1c
      (HR: 3.892; 95% CI: 1.273-11.959; p = 0.026) and low HbA1c (HR: 1.179; 95% CI:
      1.160-1.198; p = 0.039), with middle HbA1c group as the reference, also
      significantly predicted for mortality in these patients. CONCLUSIONS: HbA1c
      levels, or presence of low or high HbA1c, are associated with 18-month all-cause
      mortality in nondiabetic patients with CPD.

PMID- 21071934
TI  - Chronic nitric oxide deficiency and progression of kidney disease after renal
      mass reduction in the C57Bl6 mouse.
AB  - BACKGROUND/AIMS: the C57Bl6 mouse is resistant to chronic kidney disease (CKD)
      induced by reduction of renal mass (RRM). Nitric oxide (NO) deficiency
      exacerbates CKD progression so this study investigated whether combination of RRM
      and NO deficiency would render the C57Bl6 mouse vulnerable to CKD. METHODS: we
      used wild-type (WT) mice with RRM, chronic NO synthase (NOS) inhibition and a
      combination. Also, endothelial NOS (eNOS) knockout (KO) C57Bl6 mice were studied
      with and without RRM. Primary endpoints were albuminuria and structural damage.
      RESULTS: both nonselective (+L-NAME) and neuronal NOS 'selective' (+7NI) NOS
      inhibition greatly exacerbated the albuminuria and structural damage seen with
      RRM in the WT mice; NOS inhibition alone had little effect. The eNOS KO mice
      showed marked structural damage and significant albuminuria in the shams and RRM
      produced minimal exacerbation of structural damage although the albuminuria was
      massively amplified. CONCLUSION: these studies demonstrate that the C57Bl6 mouse
      is rendered vulnerable to RRM-induced CKD when concomitant NO deficiency is
      produced. This observation supports previous work in CKD-resistant rats and
      suggests that NO deficiency is required for progression of CKD.

PMID- 21071935
TI  - Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4
      expression in experimental diabetic nephropathy.
AB  - BACKGROUND/AIMS: although numerous studies have explored the mechanisms
      regulating the enzyme activity of NADPH oxidase in diabetic nephropathy (DN),
      little information is available for the contribution of microRNAs (miRNAs) to the
      regulation of NADPH oxidase expression. Therefore, the present study was to test
      whether miRNAs importantly contribute to the regulation of NOX4 expression, a
      major catalytic subunit of NADPH oxidase under hyperglycemia. METHODS: diabetic
      rats were induced by streptozotocin. miRNA microarray, Western blot, real-time RT
      PCR and luciferase reporter assays were employed in this study. RESULTS: among 5
      miRNAs, which are predicted to have a binding capacity to rat NOX4, the miRNA-25
      level was significantly reduced both in the kidney from diabetic rats and in high
      glucose-treated mesangial cells, accompanied by the increases in NOX4 expression
      levels. In an in vitrostudy, we found that NADPH activity was increased by 226.2%
      in miRNA-25 inhibitor transfected cells and decreased by 51.0% in miRNA-25
      precursor transfected cells. miR-25 inhibitor dramatically increased both NOX4
      mRNA and protein levels. We then showed that miR-25 negatively regulated NOX4
      expression by directly targeting the 3'-UTR by luciferase reporter assays. It was
      found that transfection of miR-25 precursor significantly decreased the
      luciferase activity of NOX4 3'-UTR by 39.5%, whereas the mutant sequence restored
      levels to 79.4%. Finally, our results indicated that the miR-25-mediated NOX4
      mRNA level may result from the regulation of mRNA stability. CONCLUSIONS: these
      findings for the first time indicate that miRNA-25 may serve as an endogenous
      gene silencing factor and contributes to the regulation of NOX4 expression and
      function in DN.

PMID- 21071936
TI  - Can the diverse family of dialysis adequacy indices be understood as one
      integrated system?
AB  - BACKGROUND: Dialysis adequacy indices are based on the amount of removed solute
      and systemized into two groups: (1) fractional solute removal (FSR, non
      dimensional), and (2) equivalent continuous clearance (ECC, ml/min), which are
      expressed using appropriate reference method for solute concentration or mass
      such as: peak, peak average, time average, and treatment time average values.
      METHODS: A review and critical analysis of the recent studies was performed.
      RESULTS: The indices are mathematically interrelated and depend on kinetic
      parameters of the treatment, as device clearance, treatment time, solute
      distribution volume, dialysis frequency. In particular, KT/V and KT can be
      directly translated to FSR and ECC using the treatment time average reference
      method. CONCLUSION: The diverse family of dialysis adequacy indices can be
      understood as one integrated system and be useful when assessing both standard
      treatment modalities and newer schedules and modalities (frequent dialysis,
      hybrid dialysis, dialysis in acute renal failure) of renal replacement therapies.

PMID- 21071937
TI  - Assessment of eptifibatide clearance by hemodialysis using an in vitro system.
AB  - BACKGROUND/AIMS: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor
      that prevents platelet aggregation. Although contraindicated in dialysis patients
      due to limited safety and dialysis data, eptifibatide is prescribed in this
      population and is associated with bleeding complications. This study was done to
      determine dialysis clearance (CL(D)) of eptifibatide using an in vitro system.
      METHODS: Three common dialyzers were tested. In vitro dialysis was performed at a
      dialysate flow rate of 500 ml/min, 'blood' flow rate (Q(B)) of 200 and 400
      ml/min, and the minimal ultrafiltration rate. Eptifibatide CL(D) and fraction
      removed were calculated for each condition. RESULTS: CL(D) ranged from 122 to 225
      ml/min and was not significantly different among the dialyzers tested. CL(D) was
      flow dependent with higher clearances observed at higher Q(B). The estimated
      fraction of eptifibatide removed was 73-83%. CONCLUSIONS: These data suggest that
      hemodialysis is an effective method to decrease the effects of eptifibatide in
      patients with impaired kidney function.

PMID- 21071939
TI  - Quitting smoking: an action that does not bounce back.

PMID- 21071938
TI  - CCN2 (CTGF) gene polymorphism is a novel prognostic risk factor for
      cardiovascular outcomes in hemodialysis patients.
AB  - BACKGROUND: The very high cardiovascular (CV) mortality and morbidity rates in
      hemodialysis (HD) patients are greatly related to atherosclerosis. CCN2
      (connective tissue growth factor/CTGF) is a profibrotic factor that is secreted
      by endothelial cells, involved in atherogenesis, promoting fibroblast
      proliferation and matrix production. CCN2 protein is significantly increased in
      complicated fibrous plaques and enhances monocyte migration into atherosclerotic
      lesions. The aim of this study was to investigate a possible association between
      CCN2 gene polymorphism and CV morbidity and mortality in HD patients. METHODS: 98
      HD patients, followed for 24 months, were genotyped for the common polymorphism
      on the CCN2 gene (G-945C). HD patient characteristics were: age 64 +/- 13 years,
      males 64%, diabetes 24%, hypertension 62%, smokers 38%, dyslipidemia 28%, all
      undergoing standard HD three times weekly. RESULTS: All-cause mortality was not
      associated with CCN2 polymorphism (G-945C). In contrast, however, the GG genotype
      was strongly associated with CV mortality: OR 13 (1.49-155), p = 0.0048.
      Interestingly, the GG genotype was also greatly associated with the serious CV
      events of stroke and myocardial infarction in surviving HD patients: OR 13.3 (2.5
      87.08), p = 0.0001. CONCLUSIONS: We demonstrate for the first time that CCN2 gene
      polymorphism is a prognostic risk factor for CV morbidity and mortality in HD
      patients. These data may have important implications for better understanding the
      link between accelerated atherosclerosis and increased mortality in HD
      population.

PMID- 21071941
TI  - Comparing different methods to assess erosive lesion depths and progression in
      vitro.
AB  - The aim of this study was to compare the precision and accuracy of 5 different
      methods applied to assess surface substance loss or changes in surface
      microhardness (SMH) on the same enamel surfaces after repeated acid exposures.
      Ground specimens from human molars were exposed to 0.01 M HCl (pH 2.2) for 6 min
      * 2 and measurements performed 3 times to estimate precision. The accuracies
      (systematic errors) were calculated against the manufacturer's calibration
      standard. Lesion depth progression was from 94 to 110%, related to repeated acid
      exposure. The precisions/accuracies were: WLI (white light interferometry),
      0.5/0.4%; SP (stylus profilometry), 4.7/0.7%; OP (optical profilometry), 1.4/12%;
      AAS (atomic absorption spectroscopy), 0.4/17% (measured calcium loss was
      converted to lesion depth). The correlation between WLI and SP was R2 = 0.98, and
      between WLI and OP it was R2 = 0.85. SMH gave information on qualitative changes
      of the surface (precision: 5.5%, accuracy: 4.0%). WLI performed best in precision
      and accuracy, but SP, OP and AAS are all relevant methods for analysing lesion
      depths and progression, SMH seems suitable for analysing minor changes in surface
      enamel only.

PMID- 21071940
TI  - Could alkali production be considered an approach for caries control?
AB  - This study investigated the relationship of arginine deiminase (ADS) and urease
      activities with dental caries through a case-control study. ADS and urease
      activities were measured in dental smooth-surface supragingival plaque and whole
      saliva samples from 93 subjects, who were in three different groups: caries-free
      (n = 31), caries-active (n = 30), and caries-experienced (n = 32). ADS activity
      was measured by quantification of the ammonia generated from the incubation of
      plaque and saliva samples in a mixture containing 50 mM arginine-HCl and 50 mM
      Tris-maleate buffer, pH 6.0. ADS-specific activity was defined as nanomoles of
      ammonia generated per minute per milligram of protein. Urease activity was
      determined by quantification of ammonia produced from 50 mM urea. For bacterial
      identification and enumeration real-time qPCR analysis was used. Groups were
      compared using Kruskal-Wallis tests. Spearman correlations were used to analyze
      plaque metabolic activity and bacterial relationships. The results revealed
      significantly higher ammonia production from arginine in saliva (1.06 vs. 0.18; p
      < 0.0001) and plaque samples (1.74 vs. 0.58; p < 0.0001) from caries-free
      subjects compared to caries-active subjects. Urease levels were about 3-fold
      higher in the plaque of caries-free subjects (p < 0.0001). Although higher urease
      activity in saliva of caries-experienced and caries-free subjects was evident, no
      significant difference was found between the groups.

PMID- 21071942
TI  - How useful is the IQCODE for discriminating between Alzheimer's disease, mild
      cognitive impairment and subjective memory complaints?
AB  - BACKGROUND: Informant questionnaires may be useful in diagnosing early dementia.
      Conflicting results were found when these questionnaires were used to
      differentiate patients with mild cognitive impairment (MCI) from healthy elderly
      subjects. We evaluated the ability of the most commonly used informant
      questionnaire, the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE), to discriminate between Alzheimer's disease (AD), MCI and subjective
      memory complaints (SMC). METHODS: Informants of 180 AD patients, 59 MCI patients
      and 89 SMC subjects who visited the Alzheimer Center of the VU University Medical
      Center between 2004 and 2007 completed the short Dutch version of the IQCODE.
      Logistic regression and receiver operating characteristic curves were used to
      evaluate the diagnostic ability of the IQCODE. RESULTS: The IQCODE was able to
      differentiate AD from MCI and SMC, but was not able to differentiate SMC from
      MCI. CONCLUSIONS: The IQCODE may be helpful in diagnosing AD but is of limited
      use in differentiating MCI from SMC.

PMID- 21071943
TI  - Transcultural influences in dementia care: observations from a psychosocial
      intervention study.
AB  - BACKGROUND: Various models of intervention for caregivers of patients with
      dementia have been described. There has been little direct comparison of cultural
      differences between countries and the effect any differences may exert on the
      outcome of caregiver interventions. AIMS: The aims of the three-country study
      (USA, Australia and the UK) were to assess whether caregiver interventions can
      still be successful when anti-dementia drugs are provided to patients, and
      whether a caregiver intervention can be successfully implemented using the same
      methods in three different English-speaking countries. In this paper, the
      cultural differences and similarities between the three countries are examined.
      METHOD: Randomised, controlled trial involving 158 patients and their caregivers
      (divided equally across three centres, New York, Sydney and Manchester) with all
      the patients receiving donepezil and the caregivers randomised to a caregiver
      intervention or treatment as usual. RESULTS: There were few differences between
      countries in the main outcome measures, and no differences between the treatment
      as-usual group and the intervention, but interesting cultural nuances were
      observed between groups. Despite these differences, the caregiver intervention
      was associated with positive results on caregiver depression across all the
      countries. CONCLUSIONS: This first multinational carer intervention study has
      emphasised the similarities between the three countries whilst highlighting
      crucial differences which may be important when planning cross-cultural studies
      in the future. The positive results achieved on caregiver depression were
      replicated across the three centres.

PMID- 21071944
TI  - D178N, 129Val and N171S, 129Val genotype in a family with Creutzfeldt-Jakob
      disease.
AB  - BACKGROUND: Fatal familial insomnia (FFI) and genetic Creutzfeldt-Jakob disease
      (CJD(D178N,)(129V)) are two phenotypes that share a common point mutation at
      codon 178 of the prion protein gene (PRNP), but differ in their polymorphism at
      codon 129 of the mutant allele. A mutation at codon 171 of the PRNP gene has been
      described in a family with a strong psychiatric history without prion disease.
      METHODS: Clinical and genetic information of a family with CJD was obtained from
      medical records and family informants. RESULTS: We identified an African-American
      family with molecular and genetically confirmed CJD(D178N,)(129V) that also
      carried the N171S, 129V polymorphism and had a strong psychiatric clinical
      presentation. CONCLUSION: This is a complex family that carries the D178N, 129V
      and N171S, 129V genotype. This report is the first description of both genotypes
      occurring within a family with genetic human prion disease.

PMID- 21071945
TI  - Prophylactic antibiotics reduce pancreatic necrosis in acute necrotizing
      pancreatitis: a meta-analysis of randomized trials.
AB  - BACKGROUND AND AIM: The use of prophylactic antibiotics to prevent infection and
      reduce mortality in patients with acute necrotizing pancreatitis (ANP) remains
      controversial. The aim of this study is to perform a systematic review of the
      data from randomized controlled trials to compare prophylactic antibiotic
      treatment of patients with ANP versus placebo. METHODS: A computerized literature
      search was conducted using Medline, PubMed, EMBase and Cochrane Central Register
      of Controlled Trials (CENTRAL) for relevant articles published in English from
      January 1990 to March 2010. MeSH terms and keywords used to identify articles
      included 'antibiotic', 'pancreatitis', and 'randomized'. Outcome measures were
      infected pancreatic necrosis (IPN), mortality, nonpancreatic infection (NPN) and
      need for surgical intervention. RESULTS: Nine trials involving 564 patients were
      included. Analysis suggested that IPN was significantly reduced by treatment with
      antibiotics (RR 0.73, 95% CI 0.54-0.98, p = 0.04). Mortality (p = 0.1), NPN (p =
      0.07), and need for surgical intervention (p = 0.17) were not significantly
      reduced by antibiotic treatment. Subsequent subgroup analysis confirmed that
      antibiotics were statistically superior to controls in reducing of infected
      necrosis (p = 0.003) and also mortality (p = 0.02) in single-blinded randomized
      controlled trials. CONCLUSION: Prophylactic antibiotic treatment reduced
      occurrence of IPN, but did not affect mortality, NPN, or surgical intervention in
      patients with ANP.

PMID- 21071946
TI  - Dyspeptic symptoms after laparoscopic large hiatal hernia repair and primary
      antireflux surgery for gastroesophageal reflux disease: a comparative study.
AB  - BACKGROUND: Several patients with gastroesophageal reflux disease suffer from
      functional dyspepsia. After laparoscopic Nissen fundoplication, these symptoms
      persist in a substantial number of patients. We hypothesized that, due to a
      higher chance of vagal nerve impairment during extensive hernia sac resection and
      esophageal mobilization, dyspeptic symptoms are more frequent after laparoscopic
      large hiatal hernia (types II-IV) repair than after primary antireflux surgery.
      METHODS: From January 2003 to December 2007, 60 consecutive patients who
      primarily underwent an antireflux fundoplication for gastroesophageal reflux
      disease and 22 consecutive patients who had large hiatal hernia repair with
      fundoplication for concomitant gastroesophageal reflux disease were included.
      According to a system combining frequency and severity, patients scored 8
      dyspeptic symptoms. Additionally, symptoms presenting preoperatively were scored
      according to the Visick grading system. RESULTS: In 43 of the 49 available
      patients (87.8%) who primarily underwent antireflux surgery and in all 20
      available patients who had hiatal hernia repair, preoperative symptoms resolved
      or improved. Mean symptom scores of all dyspeptic symptoms after surgery were
      comparable between both cohorts. General quality of life was equal in both
      cohorts. CONCLUSION: After laparoscopic large hiatal hernia repair, dyspeptic
      symptoms were present in similar frequencies as after primary antireflux surgery.

PMID- 21071947
TI  - Neurology in the People's Republic of China--an update.
AB  - The present note provides an overview of the historical development of neurology
      and its current status in the People's Republic of China, against the backdrop of
      the current massive transformation of Chinese society. We trace the origins of
      neurology in China to missionary medicine during the Republican period (1911
      1949), and describe how the discipline grows with difficulty throughout the
      subsequent decades (1950-1976). We then introduce an influential legacy of the
      post-revolutionary period, the ideal of integrating traditional Chinese medicine
      (TCM) and Western medicine, and briefly describe recent efforts to modernize
      medical education and training. Finally, we provide a brief overview of topics in
      neurology and neuropsychiatry that have a 'Chinese face', last but not least the
      successful integration of TCM and Western medicine in the treatment of
      hepatolenticular degeneration/Wilson's disease.

PMID- 21071948
TI  - Safety of pharmacological augmentation of stroke rehabilitation.
AB  - BACKGROUND: Based on experimental studies, pharmacological augmentation (PA) of
      stroke rehabilitation might be reasonable. Whether PA is beneficial in clinical
      practice is unclear. METHODS: We performed an observational study on the use of
      PA in addition to regular rehabilitative therapies in a stroke rehabilitation
      unit. Over 20 months, we systematically observed (1) the utilization rate of PA,
      (2) possible adverse events, and (3) the functional outcome of patients with
      versus without PA (non-PA). The primary outcome variable was the increase in
      abilities in activities of daily living during in-hospital rehabilitation as
      quantified by the delta 'functional independence measure' (FIM). RESULTS: Ninety
      seven of 249 (39%) patients had PA. L-Dopa was used in 63 (65%),
      acetylcholinesterase inhibitors in 33 (34%), and selective serotonin reuptake
      inhibitors in 31 (32%) PA patients. In 11 (11%) patients, PA was associated with
      delirium (n = 4), gastrointestinal symptoms (n = 4), electrolyte disorders (n =
      2), or incontinence (n = 1). All adverse events were temporary. PA patients did
      not differ from non-PA patients in age (74 vs. 73 years; p = 0.62), gender ratio,
      and stroke type (ischemia 85 vs. 82%; p = 0.49). However, compared with non-PA
      patients, PA patients were more severely affected (median NIH Stroke Scale Score
      7 vs. 4; p < 0.001; median FIM 58 vs. 85; p = 0.01). At discharge, the PA group
      had a higher median DeltaFIM compared with non-PA patients (16 vs. 9; p = 0.01).
      None of the PA patients but 5 (3.3%) of the non-PA patients had died. CONCLUSION:
      PA of stroke rehabilitation was used frequently. The absence of safety concerns
      suggests that there is scope for benefit from PA in stroke rehabilitation. A
      large randomized controlled trial seems feasible and ethically justified.

PMID- 21071949
TI  - Multiple sclerosis in Iran: a demographic study of 8,000 patients and changes
      over time.
AB  - BACKGROUND: Iran was formerly considered to be located in a low prevalence zone
      for multiple sclerosis (MS). During the last decade the number of patients has
      increased. This study was conducted to estimate the prevalence of MS in the
      capital city of the country. METHODS: We re-evaluated the files of all patients
      who had registered at the Iranian Multiple Sclerosis Society during a 10-year
      period. RESULTS: 8,146 patients (72.3% female, 27.7% male) with a female-to-male
      ratio of 2.60 had registered. Mean age of disease onset was 27.24 (SD: 8.32). A
      relapsing-remitting pattern was recognized in 84.9% of the patients. The number
      of new registrations tripled from 2002 to 2008 and the female-to-male ratio
      increased from 2 to 3.12. The prevalence of MS in Tehran is estimated to be at
      least 51.9 per 100,000. Visual impairment was the main presenting symptom.
      CONCLUSIONS: It seems that the prevalence of MS has increased to a medium-to-high
      risk level in Iran. The mean age of onset was similar to other studies but the
      calculated prevalence of early onset MS was increased. The cumulative data
      indicates that the female-to-male ratio is increasing annually.

PMID- 21071950
TI  - Improved visual hallucination by donepezil and occipital glucose metabolism in
      dementia with Lewy bodies: the Osaki-Tajiri project.
AB  - Deficits in the cholinergic system are pronounced in dementia with Lewy bodies
      (DLB) and are more severe in patients with visual hallucinations (VHs). The aim
      is to identify the occipital glucose metabolism patterns by positron emission
      tomography (PET) and the changes following donepezil treatment. 13 DLB patients
      with VHs were enrolled in the study. After the first FDG-PET study, 5 mg/day
      donepezil was administered orally, and a second PET study was performed 3 months
      later. After donepezil administration, VHs disappeared completely in 6 patients,
      and the PET studies revealed significantly decreased glucose metabolism in the
      medial occipital cortex. These results suggest that VHs in DLB were associated
      with impaired glucose metabolism in the medial occipital cortex. Donepezil
      treatment may modify regional glucose metabolism.

PMID- 21071951
TI  - Integration of cognitive impairment in the expanded disability status scale of
      215 patients with multiple sclerosis.
AB  - BACKGROUND: Estimates of the prevalence of cognitive impairment among patients
      with multiple sclerosis (MS) range between 40 and 70%. The current cerebral
      functional system (CFS) of the Expanded Disability Status Scale (EDSS) is
      subjective. AIM: To define a new cerebral functional system (NCFS) based on
      neuropsychological evaluation (NE). METHODS: We prospectively included 215 MS
      patients. NE evaluated cognitive functions. Fatigue was assessed with the Fatigue
      Impact Scale. The NCFS was devised with grades from 0 to 5, excluding depression
      but including fatigue. Grade 1 of the NCFS was integrated in the EDSS as other
      functional scores. The NCFS and new EDSS including the NCFS were compared with
      the current CFS and EDSS. RESULTS: 215 patients (69% women, 67% with relapsing
      remitting MS, median EDSS 3.0) were assessed. 98% of these patients presented
      fatigue and/or cognitive impairment with the NCFS compared to 62% with the CFS.
      The NCFS was higher than the CFS, and the EDSS had changed in 31% of the 113
      patients with an EDSS <3.5. Change in functional score was not correlated to
      current age or age at onset of MS. CONCLUSIONS: We propose a new CFS grading
      based on NE, including fatigue, and integrating grade 1 at EDSS.

PMID- 21071952
TI  - No symptomatic intracerebral hemorrhage after cardiac surgery: a 14-year
      retrospective study.
AB  - BACKGROUND: In the presence of new neurological findings occurring after cardiac
      surgery, the clinical question is whether to exclude symptomatic intracerebral
      hemorrhage (ICH), particularly in the context of routine postoperative
      anticoagulation treatment. METHODS: This is a retrospective 14-year study
      including 5,275 patients who underwent cardiovascular surgery. The control cohort
      included all patients with acute cerebrovascular accidents hospitalized in 2
      general hospitals in Jerusalem during a 2-month period in 2007 (part of a
      national survey). RESULTS: After cardiac surgery, 78 patients developed ischemic
      strokes, mostly of large-vessel etiology. These ischemic strokes occurred more
      often in patients who underwent combined operations (22/647 = 3.4% vs. 45/3,489 =
      1.3%; p = 0.0004). ICH was found in 6% of all acute cerebrovascular accidents in
      the general survey, but was absent after cardiac surgery (5 vs. 0; p = 0.02).
      CONCLUSIONS: Despite hypertension as a main risk factor and the administration of
      postoperative anticoagulation, we found that symptomatic ICH did not occur after
      cardiac surgery.

PMID- 21071954
TI  - Anti-neutrophil cytoplasmic antibody-associated vasculitis, large vessel
      vasculitis and Kawasaki disease in Japan.
AB  - Based on studies comparing the prevalence of anti-neutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis (AAV) between Japan and Europe, we have learned that
      the difference may be due to genetic background and environmental factors, but
      not to diagnosis or ELISA system for myeloperoxidase and proteinase-3 ANCA. In
      Japan, microscopic polyangiitis is the most common among AAV, but Wegener's
      granulomatosis was present in less than 2 per million patients. Also, one study
      from Hokkaido reported only 16 patients in a 27-year time frame. A recent
      retrospective study of renal vasculitis between 2000 and 2004 from Miyazaki
      prefecture in Japan reported an incidence of microscopic polyangiitis of 14.8 per
      million, but no patients with Wegener's granulomatosis or Churg-Strauss syndrome.
      In the present review, we focus on ANCA-related vasculitis in Japan: (1) AAV and
      large vessel vasculitis - Takayasu's arteritis and giant cell arteritis; (2)
      primary renal vasculitis; (3) epitopes of myeloperoxidase-ANCA in vasculitis in
      the Japanese population and comparison of ANCA-ELISA systems in Japan and Europe,
      and finally (4) children with vasculitis in Japan involving Kawasaki disease - a
      systemic vasculitis.

PMID- 21071953
TI  - Genome-wide linkage scan of bipolar disorder in a Colombian population isolate
      replicates Loci on chromosomes 7p21-22, 1p31, 16p12 and 21q21-22 and identifies a
      novel locus on chromosome 12q.
AB  - BACKGROUND/AIMS: Bipolar disorder (BP) is a severe psychiatric illness,
      characterised by alternating episodes of depression and mania, which ranks among
      the top ten causes of morbidity and life-long disability world-wide. We have
      previously performed a whole-genome linkage scan on 6 pedigrees segregating
      severe BP from the well-characterised population isolate of Antioquia, Colombia.
      We recently collected genotypes for the same set of 382 autosomal microsatellite
      markers in 9 additional Antioquian BP pedigrees. Here, we report the analysis of
      the combined pedigree set. METHODS: Linkage analysis using both parametric and
      nonparametric approaches was conducted for 3 different diagnostic models: severe
      BP only (BPI); mood disorders (BPI, BPII and major depression); and psychosis
      (operationally defined by the occurrence of at least 1 episode of hallucinations
      and/or delusions). RESULTS AND CONCLUSION: For BPI only, the most interesting
      result was obtained for chromosome 7p21.1-p22.2 under a recessive model of
      inheritance (heterogeneity LOD score = 2.80), a region that had previously been
      linked to BP in a study on Portuguese Island families. For both BPI and mood
      disorders, nonparametric analyses identified a locus on chromosome 12ct-q14
      (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not
      previously been reported as a candidate region for BP. Additional candidate
      regions were found on chromosomes 1p22-31 (mood disorders) and 21q21-22 (BPI), 2
      loci that have repeatedly been implicated in BP susceptibility. Linkage analysis
      of psychosis as a phenotype identified candidate regions on chromosomes 2q24-31
      and 16p12-q12. The finding on chromosome 16p is noteworthy because the same locus
      has been implicated by genome-wide association analyses of BP.

PMID- 21071955
TI  - Knockout of angiotensin 1-7 receptor Mas worsens the course of two-kidney, one
      clip Goldblatt hypertension: roles of nitric oxide deficiency and enhanced
      vascular responsiveness to angiotensin II.
AB  - AIMS: the present study was performed to evaluate the effects of target
      disruption of the G-protein-coupled receptor Mas for angiotensin 1-7 [Ang(1-7)]
      in knockout mice on the course of two-kidney, one-clip (2K1C) Goldblatt
      hypertension. METHODS: knockout and wild-type mice underwent clipping of one
      renal artery. Blood pressure (BP) was monitored by radiotelemetry. The mice were
      either untreated or chronically treated with the superoxide (O(2)(-)) scavenger
      tempol (400 mg/l) or the inhibitor of NADPH oxidase apocynin (1 g/l) administered
      in drinking water. RESULTS: knockout mice responded to clipping by accelerated
      increases in BP and the final BP was significantly higher than that in wild-type
      mice. Chronic treatment with tempol or apocynin elicited similar antihypertensive
      effects in 2K1C/knockout as in 2K1C/wild-type mice. Acute nitric oxide synthase
      inhibition caused greater BP increases in 2K1C/wild-type than in 2K1C/knockout
      mice. CONCLUSION: our present findings support the notion that the angiotensin
      converting enzyme 2-Ang(1-7)-Mas axis serves as an important endogenous
      physiological counterbalancing mechanism that partially attenuates the
      hypertensinogenic actions of the activated renin-angiotensin system. The
      impairment in this axis may contribute to the deterioration of the course of 2K1C
      Goldblatt hypertension.

PMID- 21071957
TI  - Estimation of oxidative stress markers in chronic kidney disease.
AB  - Changes mediated by oxidative stress are thought to be involved with
      atherosclerosis in patients with chronic kidney disease (CKD). The purpose of
      this study was to analyze the markers of oxidative damage and the activity of
      antioxidative enzymes as well as the total antioxidant capability in patients
      with different stages of CKD, both conventionally treated and dialyzed. We
      evaluated the oxidative modification of lipids (by oxidized low-density
      lipoprotein and malonodialdehyde levels) and proteins (by advanced oxidation
      protein products level). We also assessed the activity of paraoxonase-1 and
      glutathione peroxidases and total antioxidant status. Compared with the control
      group, the uremic patients, both dialyzed and nondialyzed, had higher levels of
      all studied plasma oxidative stress markers and decreased activity of
      antioxidative enzymes. Our results lead us to conclude that oxidative stress
      seems to be related rather to the uremic state than to the dialysis treatment. We
      also showed that estimating total antioxidant status in a simple test is
      unreliable for assessing the antioxidant ability of patients with CKD.

PMID- 21071956
TI  - High-salt diet and hypertension: focus on the renin-angiotensin system.
AB  - A high-salt diet is one of the major risk factors in the development and
      maintenance of hypertension. Numerous experimental and observational studies have
      confirmed the association of sodium intake with blood pressure levels. The
      effects of a high-salt diet are related to the function of the renin-angiotensin
      system, which is normally suppressed by a high-salt diet. Endothelial dysfunction
      probably plays an important role in the influence of high sodium intake on blood
      pressure, although the exact mechanisms remain elusive. Genetic factors are known
      to be very important, and various consomic and congenic rat strains as animal
      models have proven to be very useful in bringing us a step closer to
      understanding the interaction between salt intake and hypertension. In this
      article, experimental data obtained in studies on animals and humans, as well as
      epidemiological data are reviewed.

PMID- 21071959
TI  - Detection of markers of cardiovascular and renal risk in Cuba: Isle of Youth
      Study (ISYS).
AB  - Chronic vascular diseases constitute a growing global health problem. OBJECTIVES:
      To (a) determine marker positivity for renovascular damage in the total adult
      population of the Isle of Youth, Cuba; (b) describe marker association with
      common risk factors for renal and related chronic vascular conditions, and (c)
      identify best predictors of renovascular damage. METHODS: Previous informed
      consent was obtained, the population studied was 55,646, and subjects were aged
      >=20 years. Blood pressure, weight and height were measured and a questionnaire
      applied. Urine markers for renovascular damage (hematuria, proteinuria and
      microalbuminuria) were also determined. RESULTS: Positive markers were detected
      in 21.3%: hematuria (12.6%), microalbuminuria (6.8%), proteinuria (0.9%), and
      proteinuria + hematuria (0.9%). Risk factors were highly prevalent: 15.1% were
      aged >=60 years; 32.3% overweight, 13.9% obese, and 25.1% smokers. Prevalence of
      high blood pressure (30%), diabetes mellitus (5.4%) and cardiovascular disease
      (5%) was also high, while cerebrovascular disease registered 0.9%. Markers were
      more prevalent in older people and in those suffering from diabetes mellitus,
      high blood pressure, cardiovascular and cerebrovascular disease, overweight or
      obesity. Risk factor regression tree analysis identified hypertension as the best
      predictor of renovascular damage. CONCLUSIONS: Adult population-wide screening
      revealed hidden morbidity and permitted better risk stratification. Results serve
      to inform community-based multidisciplinary and intersectoral disease prevention
      and management.

PMID- 21071958
TI  - Antifibrotic effects of pioglitazone at low doses on the diabetic rat kidney are
      associated with the improvement of markers of cell turnover, tubular and
      endothelial integrity, and angiogenesis.
AB  - BACKGROUND/AIMS: Pioglitazone and other thiazolidinediones are renoprotective in
      diabetic nephropathy at doses that normalize glycemia, presumably as a
      consequence of glycemic control. However, low doses of pioglitazone that did not
      normalize glycemia in rat models of type 2 diabetes prevented tubulointerstitial
      fibrosis and glomerulosclerosis through counteracting inflammation, oxidative
      stress, cell cycle arrest, and fibrosis. The current work tested whether this low
      dose treatment also reduces other fibrosis and inflammation factors in the
      diabetic kidney and prevents tubular cell loss, endothelial damage, and abnormal
      angiogenesis. METHODS: ZDF fa/fa rats (ZDF) were fed for 4 months chow with
      0.001% pioglitazone, and the untreated ZDF and the non-diabetic lean Zucker rats
      (LZR) received regular chow. Proteinuria, creatinine clearance, blood pressure,
      and renal quantitative histopathology markers were determined. RESULTS:
      Correction of renal function in ZDF by pioglitazone, occurring with a glycemia
      >250 mg/dl, was accompanied by normalization of the renal levels of connective
      tissue growth factor and fibronectin (fibrosis), TNF-alpha, interleukin-6 and MCP
      1 (inflammation), megalin (tubular cells), the PCNA/caspase-3 ratio (positive
      cell turnover), VEGF (abnormal angiogenesis), and the ratio between eNOS and iNOS
      (endothelial dysfunction). CONCLUSION: This supports mechanisms for the
      renoprotective effects of pioglitazone in diabetes additional to glycemic
      control.

PMID- 21071960
TI  - Prognostic implication of plasma osteopontin levels in patients with chronic
      kidney disease.
AB  - AIMS: To assess (a) plasma osteopontin (pOPN) in a cohort of chronic kidney
      disease (CKD) patients; (b) the relationship between pOPN and aortic
      calcification and stiffness, and (c) the association between pOPN and the overall
      and cardiovascular mortality risk. METHODS: pOPN, the abdominal aortic
      calcification score and pulse wave velocity (PWV) were determined in 94 CKD
      patients (68 +/- 13 years; 60% males; 31% at CKD stages 2-3, 31% at stages 4-5,
      38% at stage 5D), prospectively followed for mortality. RESULTS: pOPN was higher
      in CKD patients than in controls. Interleukin (IL)-6 (r(2) = 0.086; p = 0.004),
      CRP (r(2) = 0.046; p = 0.038), iPTH (r(2) = 0.065; p = 0.014), albumin (r(2) =
      0.210; p < 0.0001) and statin use (r(2) = 0.038; p = 0.059) were associated with
      pOPN. There was no association between pOPN and the aortic calcification score or
      PWV. During follow-up (969 +/- 405 days), 32 patients died. In crude analysis,
      pOPN >167 ng/ml predicted overall and cardiovascular mortality (p = 0.02 and
      0.01, respectively), but this effect was lost after adjustment for albumin or IL
      6. CONCLUSIONS: pOPN is elevated from the early stages of CKD onward. We found no
      associations between pOPN and the aortic calcification score or the PWV. The
      positive association between pOPN and clinical outcomes was dependent of the
      patients' inflammatory status.

PMID- 21071962
TI  - Prediction of mortality in patients undergoing maintenance hemodialysis by
      Charlson Comorbidity Index using ICD-10 database.
AB  - BACKGROUND/AIMS: Many patients with end-stage renal disease have additional
      comorbidities that are important to clinical study and impact the patient's
      outcome. The Charlson Comorbidity Index (CCI) is a popular tool and a strong
      predictor of outcome in end-stage renal disease patients. We obtained comorbidity
      data from the hospital discharge database using the International Classification
      of Disease, 10th revision (ICD-10) and analyzed the mortality rate in incident
      patients undergoing maintenance hemodialysis (HD). METHODS: We evaluated the
      medical records of a total of 456 patients on HD (58 +/- 14 years of age, 56%
      males). We calculated CCI scores at the start of HD with information from the
      hospital discharge summary according to the ICD-10 code. We then analyzed patient
      mortality according to these CCI scores. RESULTS: The percentages of patients
      that had diabetes with end-organ damage (51.1%), congestive heart failure (9.9%),
      coronary artery disease (8.1%) and stroke (6.8%) were identified. CCI scores were
      5.09 +/- 2.01 (range 2-11). Four comorbidity groups were established by quartile
      ranking of the CCI scores: low, moderate, high and very high. The mortality rates
      were: 0.83, 7.70, 14.09 and 18.69 deaths/100 patient-years, respectively (p =
      0.001). Compared with the low comorbidity group, the hazard ratios for mortality
      were 9.22 (95% CI 3.29-25.84) for the moderate group, 16.77 (95% CI 5.97-47.11)
      for the high group, and 22.37 (95% CI 8.08-61.93) for the very high group.
      CONCLUSIONS: The CCI scores using the ICD-10 database information were
      significant predictors of mortality in incident patients undergoing maintenance
      HD.

PMID- 21071961
TI  - Serum 25(OH)-cholecalciferol concentration is associated with hemoglobin level
      and erythropoietin resistance in patients on maintenance hemodialysis.
AB  - BACKGROUND: Resistance to erythropoiesis-stimulating agents (ESAs) has been
      observed in patients with chronic kidney disease (CKD) and it is associated with
      clinical outcomes. The presence of ESA resistance cannot always be explained by
      the known risk factors of the condition, suggesting that additional factors may
      be involved. We wanted to test the hypothesis that vitamin D insufficiency is
      associated with lower hemoglobin (Hb) and ESA resistance in patients on
      maintenance hemodialysis (HD). METHODS: Data from patients receiving maintenance
      HD in a single dialysis center were extracted from the medical records in a
      retrospective chart review. Basic patient characteristics and laboratory data
      including Hb, serum albumin, intact parathyroid hormone and serum 25(OH)
      cholecalciferol (25(OH)D(3)) levels were collected. ESA dose and Kt/V were
      extracted from the dialysis charts. Correlation analysis and multivariate linear
      regression analysis were used to reveal potential independent associations
      between clinical and laboratory parameters and ESA resistance. RESULTS: Data from
      142 patients were analyzed. Serum 25(OH)D(3) concentration was significantly
      correlated with Hb (rho = 0.186, p < 0.05) and also with ESA dose/Hb index (rho =
      0.230, p < 0.01). In multivariable regression analyses, serum 25(OH)D(3)
      concentration remained significantly associated with both Hb and ESA dose/Hb
      index after controlling for potentially important confounders. CONCLUSION: Serum
      25(OH)D(3) concentration is independently associated with erythropoietin
      responsiveness in CKD patients on maintenance HD. If this association will be
      confirmed, treatment trials looking at the effect of vitamin D supplementation on
      anemia treatment in CKD patients may be warranted.

PMID- 21071963
TI  - Endoscopic subureteral polydimethylsiloxane injection and prevention of recurrent
      acute graft pyelonephritis.
AB  - BACKGROUND/AIMS: Vesicoureteral reflux (VUR) is an important factor in recurrent
      acute graft pyelonephritis (AGPN). In this study, we evaluated the effect of
      subureteral polydimethylsiloxane (PDS) injection on recurrent AGPN in renal
      transplant recipients with VUR. METHODS: 64 renal transplant recipients with
      recurrent AGPN were included, 31 (48%) of whom had VUR. Of the patients with VUR,
      19 (61%) were treated with PDS and the others were managed with antibiotics. The
      effect of PDS treatment on recurrent AGPN was evaluated in terms of the overall
      success rate, the success rate according to VUR grade, and the number of PDS
      treatments. RESULTS: The overall success rate of PDS injection was 63%, and the
      number of AGPN episodes was significantly reduced after injection compared with
      the number before injection (0.21 vs. 1.34 times/person-year, respectively, p <
      0.05). The success rate of PDS treatment differed with the VUR grade (50% in
      grade 1, 33% in grade 2, 75% in grade 3, and 67% in grade 4). The success rate in
      the first trial was 67% and in the second it was 50%. CONCLUSION: PDS injection
      is an effective treatment for recurrent AGPN in renal allograft recipients with
      VUR.

PMID- 21071964
TI  - Local expression of C-reactive protein is associated with deteriorating graft
      function in acute and chronic failure of kidney transplants.
AB  - BACKGROUND: C-reactive protein (CRP) is a key molecule in inflammation and tissue
      homeostasis and is produced locally by renal tubular epithelial cells. Its
      significance of expression in contrast to expression of cytotoxic T cell (CTL)
      markers remains to be elucidated. METHODS: By means of real-time PCR, we
      determined mRNA levels of CRP in 66 renal allograft biopsies with acute allograft
      failure and in 34 biopsies with chronic dysfunction. Results were compared to
      expression of CTL components (perforin, granzyme B) and were correlated with
      histologic diagnoses and outcome. RESULTS: CTL markers were found in most
      biopsies, and thus were not specific for particular histologies, although
      expression levels increased significantly with Banff rejection grades. Expression
      of CRP was highly specific for rejection episodes in acute failure (p < 0.0001)
      as well as for transplant glomerulopathy or de novo/recurrent glomerulonephritis
      in chronic failure (p < 0.005). Finally, the presence of CRP expression in renal
      allografts was associated with a deteriorating 1-year graft function in acute (p
      < 0.01) as well as chronic allograft dysfunction (p = 0.077). CONCLUSIONS: Our
      data suggest local CRP expression of kidney transplants as an indicator for
      pathologic entities associated with unfavorable outcomes in the early and late
      course of kidney transplants.

PMID- 21071965
TI  - A theoretical and practical course on urine microscopy in Nigeria: a model for
      nephrological skill transfer.
AB  - BACKGROUND: In the developing world, the diagnostic power of nephrologists is
      heavily limited by financial, technical and human resource constraints. Urine
      microscopy (UM) is a basic, inexpensive and relatively simple diagnostic tool,
      which supplies irreplaceable information. Recently, a theoretical and practical
      course on UM was organized during the 22nd annual meeting of the Nigerian Society
      of Nephrology. METHODS: The 2-day course was based on power point presentations
      and on examination of true urine samples by means of a microscope equipped with
      phase contrast, polarized light and a video camera for projection of the
      findings. RESULTS: The presentations described were the methodology, the
      particles of the urine sediment and their clinical interpretation, the urine
      sediment in different clinical conditions, and 12 clinical cases, which
      demonstrated the value of UM in clinical practice. Practical sessions showed the
      most important urine particles, and how they could be identified and combined
      into urine profiles. More than 97% of the participants found the course to be
      useful and practicable and a UM program was actually started in 1 Nigerian center
      a few days after the course. CONCLUSION: This course demonstrated that
      nephrological skills can be transferred from the developed to the developing
      world without large financial investments.

PMID- 21071966
TI  - Dialyzers designed to increase internal filtration do not result in significantly
      increased platelet activation and thrombin generation.
AB  - INTRODUCTION: To increase middle molecule clearances, high-flux dialyzers with
      increased internal filtration have been developed. However, dialyzer design and
      structure may affect thrombin generation and platelet activation, thereby risking
      increased clotting and reduced dialyzer clearances. METHODS: Coagulation
      parameters, platelet, white cell and endothelial activation markers were measured
      prior to and following dialysis sessions in 12 patients using two different
      dialyzers designed for increased internal filtration. RESULTS: Prior to dialysis,
      patients had evidence of activation of coagulation with increased factor VIII:C,
      thrombin-antithrombin complexes and prothrombin fragment 1+2, increased platelet
      activation, with raised platelet factor 4, beta-thromboglobulin levels and
      increased fibrinolysis (raised D-dimers). Dialysis was associated with the
      release of soluble platelet integrin, sP selectin, increased endothelial
      activation with increased levels of von Willebrand factor (vWF) antigen (vWF:Ag)
      and vWF propeptide (vWF:pp) and sE selectin. There was no difference in
      tinzaparin levels at the end of the dialysis session using either dialyzer, as
      shown by anti-Xa activity - 0.145 +/- 0.027 versus 0.11 +/- 0.017 IU/ml,
      respectively. CONCLUSION: Haemodialysis patients have an inflammatory phenoytype,
      characterized by increased activation of coagulation, platelets and also
      fibrinolysis. However, dialyzers designed to increase internal filtration did not
      significantly increase platelet activation or thrombin generation.

PMID- 21071967
TI  - Renal genetics and clinical practice: the present and the possible.

PMID- 21071968
TI  - Practical genetics for autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common mendelian
      disorder of the kidney and accounts for ~5% of end-stage renal disease in North
      America. It is characterized by focal development of renal cysts which increase
      in number and size with age. Mutations of PKD1 and PKD2 account for most cases.
      Although the clinical manifestations of both gene types overlap completely, PKD1
      is associated with more severe disease than PKD2, with larger kidneys and earlier
      onset of end-stage renal disease. Furthermore, marked within-family renal disease
      variability is well documented in ADPKD and suggests a strong modifier effect
      from as yet unknown genetic and environmental factors. In turn, the significant
      inter- and intra-familial renal disease variability poses a challenge for
      diagnosis and genetic counseling. In general, renal ultrasonography is commonly
      used for the diagnosis, and age-dependent criteria have been defined for subjects
      at risk of PKD1. However, the utility of the PKD1 ultrasound criteria in the
      clinical setting is unclear since their performance characteristics have not been
      defined for the milder PKD2 and the gene type for most test subjects is unknown.
      Recently, highly predictive ultrasound diagnostic criteria have been derived for
      at-risk subjects of unknown gene type. Additionally, both DNA linkage and gene
      based direct sequencing are available for the diagnosis of ADPKD, especially in
      subjects with equivocal imaging results, a negative or indeterminate family
      history, or in younger at-risk individuals being evaluated as potential living
      related kidney donor. This review will highlight the utility and limitations of
      clinical predictors of gene types, imaging- and molecular-based diagnostic tests,
      and present an integrated approach for evaluating individuals suspected to have
      ADPKD.

PMID- 21071969
TI  - Towards the integration of genetic knowledge into clinical practice.
AB  - The past three decades have seen a revolution in molecular biology and genetics
      that have changed the way we define disease, diagnose it, understand
      pathogenesis, initiate new treatments and assess individual responsiveness to
      intervention. The 'new genetics' has made its biggest impact on monogenic or
      'rare' diseases, although its impact is increasingly being felt in the
      polymorphic so-called 'common' diseases. In this brief review, we summarise the
      efforts being made to improve the management of rare kidney diseases in Europe
      through the EUNEFRON network and also the rapid progress being made
      internationally in translating genetic knowledge for patient benefit in autosomal
      dominant polycystic kidney disease, the most common inherited kidney disease.

PMID- 21071970
TI  - Uromodulin-associated kidney disease.
AB  - Uromodulin (Tamm-Horsfall glycoprotein) is the most common protein excreted in
      the urine of healthy individuals, yet its function remains unclear. Mutations in
      the UMOD gene encoding uromodulin result in a marked decrease in the synthesis of
      uromodulin, as well as the accumulation of abnormal uromodulin in tubular cells,
      leading to tubular cell death. UMOD gene mutations are responsible for the
      autosomal dominant inheritance of chronic interstitial disease, leading to the
      need for renal replacement in the third through seventh decades of life.
      Individuals with UMOD mutations also suffer from hyperuricemia in childhood, and
      often suffer from gout in their teenage years. A similar clinical syndrome
      causing the autosomal dominant inheritance of chronic kidney disease,
      hyperuricemia, and anemia has recently been attributed to mutations in the REN
      gene encoding renin. Recently, polymorphisms in the UMOD gene have been found
      responsible for increased urinary uromodulin production and an increased risk of
      chronic kidney disease. This review summarizes information on uromodulin biology
      and clinical manifestations of mutations in the UMOD gene, as well as similar
      inherited interstitial diseases. It provides new information regarding UMOD gene
      polymorphisms and their association with chronic kidney disease.

PMID- 21071971
TI  - Haemolytic uraemic syndrome.
AB  - Atypical haemolytic uraemic syndrome (aHUS) is a disease characterized by
      complement overactivation in which inherited defects in complement genes and
      acquired autoantibodies against complement regulatory proteins have been
      described. Identification of the underlying defect can both predict disease
      outcome and guide treatment. The ability to remove inhibitory autoantibodies and
      hyper-active complement components in addition to its ability to replace
      defective complement regulators means that plasma exchange is currently first
      line therapy. In those with factor H and factor I mutations who do progress to
      end-stage renal failure, renal transplantation usually fails due to recurrent
      HUS. In this situation, combined liver-kidney transplantation has been suggested
      to correct the underlying genetic defect. Newer agents, such as the complement
      inhibitor eculizumab, may herald a new era in the treatment of aHUS.

PMID- 21071972
TI  - Blood pressure, proteinuria and nephropathy in Fabry disease.
AB  - BACKGROUND/AIMS: Fabry disease is an X-linked disorder leading to abnormal
      accumulation of glycosphingolipids with multisystem involvement, including
      cardiac, renal, dermatologic and neurologic manifestations. Fabry nephropathy,
      specifically proteinuria and progressive chronic kidney disease, have taken
      center stage over the past decade, defining disease outcomes as well as mortality
      associated with Fabry disease. Systemic blood pressure among patients with Fabry
      disease is relatively low, compared to other forms of proteinuric chronic kidney
      disease. METHODS: This review is based on a systematic survey of recent
      publications that describe the diagnosis and treatment of Fabry nephropathy in
      adults. RESULTS: A high percentage of patients with Fabry disease have been shown
      to have proteinuria, and a small but significant percentage of Fabry patients
      have overt hypertension. Recent efforts have focused on the use of angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers (ACEIs/ARBs) in
      addition to enzyme replacement therapy (ERT) for treatment of Fabry nephropathy.
      The proven beneficial effects of ACEI/ARBs for more common forms of proteinuric
      kidney disease have been extrapolated to the treatment of Fabry nephropathy. The
      overall treatment goal with ACEIs/ARBs, in combination with ERT, is reduction of
      urinary protein excretion to less than 500 mg/day, and stabilization of the
      decline of kidney function to -1 ml/min/1.73 m(2)/year. ERT alone, in the absence
      of ACEIs/ARBs does not decrease proteinuria in Fabry patients. We present the
      prevalence of proteinuria, kidney disease and hypertension in Fabry disease and
      discuss treatment goals for the treatment of this unusual form of proteinuric
      kidney disease. CONCLUSION: There are some practical challenges to the use of
      standard antiproteinuric therapy in Fabry disease that need to be addressed to
      optimize patient outcome, with the expectation that kidney function can be
      preserved with the combination of ERT and ACEI/ARB therapy.

PMID- 21071973
TI  - Genetic variations and transplant outcomes.
AB  - Extensive genetic variation has been described in molecules regulating innate and
      adaptive immunity, pharmacokinetics, coagulation, and fibrosis. However, large
      prospective studies need to be performed to define the clinical consequences of
      such variation and the potential benefits of genotyping these markers for
      patients. The purpose of this review is to summarize recent data describing
      associations of polymorphisms in both immunological and non-immunological
      molecules with transplant outcomes, and discuss their clinical implications and
      limitations.

PMID- 21071974
TI  - Genetics of chronic kidney disease.
AB  - The current review collates what is already known of the genetics of chronic
      kidney disease (CKD), and focuses on new trends in genome-wide assessment of the
      inherited component of susceptibility to this condition. Early efforts to
      identify kidney disease susceptibility genetic loci using linkage and candidate
      gene strategies proved disappointing. More recently, genome-wide association
      studies have yielded highly promising results suggesting a number of potential
      candidate genes and genomic regions that may contribute to the pathogenesis of
      CKD. Renal failure susceptibility genes identified by these methods, such as
      MYH9, have yielded novel insights into the pathogenesis of CKD. Genome-wide
      association studies of CKD are beginning to define the genomic architecture of
      kidney disease and will impact our understanding of how genetic variation
      influences susceptibility to this condition.

PMID- 21071975
TI  - Genetic disorders of glomerular basement membranes.
AB  - This review provides current information about glomerular disorders that arise
      directly from inherited abnormalities in extracellular matrix proteins intrinsic
      to the glomerular basement membrane (Alport syndrome, thin basement membrane
      nephropathy, HANAC syndrome and Pierson syndrome). The authors also discuss
      disorders involving genetic defects in cellular proteins that result in
      structural defects in glomerular basement membranes (MYH9-related disorders, nail
      patella syndrome).

PMID- 21071976
TI  - Genetics in clinical practice: nephrotic and proteinuric syndromes.
AB  - Nephrotic syndrome (NS) is a disorder of the glomerular filtration barrier, a
      highly specialised tri-layer structure with unique functional properties. Recent
      advances emanating from the field of molecular genetics have revealed the
      podocyte as probably the central player in the control of glomerular filtration.
      More specifically, the cell-cell junction between adjacent podocyte foot
      processes, the slit diaphragm, has been revealed to be made up of a sophisticated
      multi-protein complex which dynamically controls foot process architecture via
      signalling to the actin cytoskeleton. Key genes that have been identified from
      the study of inherited NS include those encoding nephrin, podocin, TRPC6 and
      alpha-actinin-4, and more remain to be found. It is now possible to identify
      genetic causes underlying a proportion of NS presenting at any age, and this
      review aims to help describe genetic NS according to age of presentation, and
      provide information on known mutations. The next big challenge for clinicians and
      researchers is to translate the molecular information learnt into the
      understanding of acquired, non-inherited forms of the disease.

PMID- 21071977
TI  - Tuberous sclerosis complex renal disease.
AB  - Although not as common as other genetic renal diseases such as autosomal dominant
      polycystic kidney disease, patients with tuberous sclerosis complex frequently
      have significant renal involvement. Recent revelations in the cell biology of
      these renal disease manifestations as well as effective therapies for tuberous
      sclerosis complex-related renal issues have heralded hope of improved renal
      survival and improved quality of life for the TSC patient. This review
      specifically addresses some of the major renal manifestations of this disease.

PMID- 21071978
TI  - Genetics of familial renal cancers.
AB  - Renal cell carcinoma (RCC) is a heterogeneous disorder. A variety of
      histopathological subtypes occur, and the molecular mechanisms associated with
      these subtypes can differ. Only a small fraction of all RCC is accounted for by
      inherited cases (e.g. von Hippel-Lindau disease, Birt-Hogg-Dube syndrome,
      hereditary leiomyomatosis renal cell cancer), but such cases can pose specific
      clinical management issues and offer opportunities for early cancer detection and
      prevention. Furthermore, inherited RCC syndromes have provided important
      paradigms to study the molecular basis of renal tumourigenesis. The
      identification of molecular mechanisms of carcinogenesis in inherited RCC
      syndromes should lead to novel approaches to personalized therapeutics.

PMID- 21071979
TI  - Mechanisms of nephronophthisis and related ciliopathies.
AB  - An emerging group of human genetic diseases termed 'ciliopathies' are caused by
      dysfunction of two functionally and physically associated organelles, the
      centrosome and cilium. These organelles are central to perception of the physical
      environment through detection of a diverse variety of extracellular signals such
      as growth factors, chemicals, light and fluid flow. Many of the described
      ciliopathies display multi-organ involvement, with renal and retina being the
      most commonly affected. Nephronophthisis is a recessive disorder of the kidney
      that is the leading cause of end-stage renal failure in children. Through
      positional cloning, many of the causative mutations have been mapped to genes
      involved in centrosome and cilia function. In this review, we discuss the
      identified causative mutations that give rise to nephronophthisis and how these
      are related to the disease etiology in both the kidney and other organs.

PMID- 21071981
TI  - Selective blockade of oxytocin and vasopressin V(1a) receptors in anaesthetised
      rats: evidence that activation of oxytocin receptors rather than V(1a) receptors
      increases sodium excretion.
AB  - BACKGROUND: Although it is known that moderate-to-high doses of the
      neurohypophysial hormones oxytocin and vasopressin are natriuretic, doubts remain
      over the identity of the receptors responsible. To address this issue, we have
      used highly selective antagonists of oxytocin and vasopressin receptors in
      animals with elevated endogenous circulating levels of the 2 hormones. METHODS:
      Rats were anaesthetised and prepared surgically for clearance studies, thereby
      raising plasma oxytocin and vasopressin concentrations. Sodium excretion,
      glomerular filtration rate and lithium clearance (an index of end-proximal fluid
      delivery) were measured: first during a control period, then after administration
      of the selective oxytocin receptor antagonist desGly-NH(2),d(CH(2))(5)[D
      Trp(2),Thr(4),Dap(5)]OVT, the selective vasopressin V(1a) receptor antagonist
      d(CH(2))(5)[Tyr(Me)(2),Dab(5)]AVP, or vehicle alone. RESULTS: Absolute and
      fractional sodium excretion fell in rats given the oxytocin antagonist (by 32 and
      27%, respectively, compared with corresponding values in vehicle-infused rats),
      but not in those given the V(1a) antagonist or vehicle. Antinatriuresis was
      associated with a small reduction in the ratio of sodium clearance to lithium
      clearance (an index of the fraction of distally delivered sodium that escapes
      reabsorption in the distal nephron). CONCLUSIONS: These results corroborate
      previous studies showing that activation of oxytocin receptors increases sodium
      excretion and imply that the natriuretic effect of elevated plasma vasopressin
      concentrations results from stimulation of oxytocin receptors.

PMID- 21071982
TI  - Disorders of the renal proximal tubule.
AB  - Following glomerular filtration, the bulk of solutes are reabsorbed in the
      proximal tubule to prevent excessive losses of vital metabolites. In this nephron
      segment, reabsorption is largely active via dedicated transporters. Hereditary
      defects in proximal tubular function are characterized by malabsorption affecting
      amino acids, glucose, potassium, phosphate, bicarbonate, low-molecular-weight
      proteins and other solutes handled by this nephron segment. Dysfunction may be
      isolated or generalized (Fanconi syndrome). Defects in specific transporters lead
      to increased urinary excretion of substrates, which are often diagnostic. In
      others, extrarenal gene expression causes a multisystem phenotype. In this
      review, we will give a short overview of the molecular genetics, clinical
      picture, pathophysiology and treatment of genetically defined proximal
      tubulopathies.

PMID- 21071980
TI  - Expression of Transcription Factor GATA-6 in Alveolar Epithelial Cells Is Linked
      to Neonatal Lung Disease.
AB  - BACKGROUND: Premature birth and respiratory distress syndrome (RDS) are risk
      factors for disturbed lung development and bronchopulmonary dysplasia (BPD). The
      molecular mechanisms related to prematurity and BPD remain largely unknown.
      Epithelial expression of the transcription factor GATA-6 has been implicated in
      normal and abnormal murine lung development. OBJECTIVES: The possible involvement
      of GATA-6 in the normal development and in RDS and BPD was investigated in the
      human and baboon lung. METHODS: Immunohistochemistry was used to study the
      expression of GATA-6 and thyroid transcription factor 1 in lung specimens from
      different age groups of human and baboon fetuses and newborns with lung disease.
      Furthermore, the regulatory role of TGF-beta1 in GATA-6 expression was
      investigated in human pulmonary epithelial cell lines using RT-PCR. RESULTS: GATA
      6 expression increased in the developing human airway epithelium along with
      advancing gestation, but diminished to negligible at birth. In RDS, GATA-6
      expression was enhanced at 5-7 days after birth, and decreased thereafter. In
      BPD, the expression of GATA-6 in alveolar epithelial cells was low. These results
      were confirmed and extended using an established baboon model of prematurity. The
      in vitro experiments revealed that TGF-beta1 induces GATA-6 and thyroid
      transcription factor 1 expression in lung epithelial cells. CONCLUSIONS: Our
      results suggest that the expression of GATA-6 at the early stages of the preterm
      lung may be related to impaired postnatal alveolar development.

PMID- 21071983
TI  - Genetic disorders of NaCl transport in the distal convoluted tubule.
AB  - The distal convoluted tubule (DCT) reabsorbs 5-10% of filtered Na, and is an
      important site for regulation of Na balance. Additionally, the amount and
      composition of the tubular fluid that leaves the DCT affects H and K secretion in
      more distal nephrin segments. Mutations in five genes whose products are
      expressed in the DCT demonstrate these points and help to define the mechanisms
      by which the DCT contributes to control of electrolyte balance and volume. Loss
      of function mutations in the apical thiazide-sensitive NaCl cotransporter and the
      basolateral K channel Kir4.1, and activating mutations in the Ca-sensing receptor
      cause a phenotypically similar salt wasting syndrome. Mutation in two recently
      identified kinases, WNK1 and WNK4 cause a salt-retaining syndrome through
      increased apical expression of NaCl cotransporter. Recent studies indicate that
      these genes are important not only for understanding the physiology of the distal
      nephron, but that they and others may also contribute to blood pressure variation
      in the general population.

PMID- 21071984
TI  - Disorders of calcium metabolism.
AB  - The genetic contribution to calcium metabolism is well recognized. Many of the
      proteins that contribute to calcium homeostasis through intestinal absorption,
      bone deposition and resorption, renal reabsorption and the molecules regulating
      these processes have been identified. Mutations in many of the genes coding for
      these proteins have been identified and often have clear clinical phenotypes.
      These mutations are generally rare with large effect sizes and a high degree of
      penetrance. As monogenetic diseases, they have a mendelian inheritance pattern
      and have been identified with traditional family-based linkage studies. A great
      deal of progress has been made in the understanding of the physiology of calcium
      metabolism; however, it remains an evolving field. The identification of the
      monogenetic etiology of disease has contributed greatly to our understanding of
      calcium handling and homeostasis. Transgenic animal models of these diseases
      continue to offer new insights into the mechanisms of calcium metabolism and its
      regulation. The purpose of this review is to briefly outline calcium metabolism
      focusing on the mechanisms of intestinal absorption and renal reabsorption as a
      framework to review the monogenic causes of dysregulated calcium metabolism.

PMID- 21071985
TI  - Disorders of water and acid-base homeostasis.
AB  - Disorders of water balance lead either to dehydration or overhydration. Because
      there is an intimate relationship between water and sodium concentration (water
      generally following salt), one can distinguish hypotonic, isotonic and hypertonic
      dehydration and the same for overhydration. The vast majority of water balance
      disorders are acquired. In this article, the focus is on the inherited disorders
      both of water (nephrogenic diabetes insipidus) and acid-base balance. Both
      acidosis and alkalosis can arise from primary tubular ion transport
      abnormalities. The alkaloses are usually secondary to salt handling problems,
      whereas the renal tubular acidoses are often a consequence of primary
      abnormalities of acid-base transporters.

PMID- 21071986
TI  - Renal stone disease.
AB  - BACKGROUND/AIMS: Renal stone disease may be seen as a clinical symptom of an
      underlying pathological process predisposing to crystallization within the renal
      tract. Renal stones may be comprised of calcium salts, uric acid, cystine and
      various other insoluble complexes. Nephrolithiasis may be the manifestation of
      rare single gene disorders or part of more common idiopathic renal stone-forming
      diseases. METHODS AND RESULTS: Molecular genetics has allowed significant
      progress to be made in our understanding of certain stone-forming conditions. The
      molecular defect underlying single gene disorders often contributes to a
      significant metabolic risk factor for stone formation. In contrast, idiopathic
      renal stone formation relates to the interplay of environmental, dietary and
      genetic factors, with hypercalciuria being the most commonly found metabolic risk
      factor. Candidate genes for idiopathic stone formers have been identified using
      numerous approaches, some of which are outlined here. Despite this, the genetic
      basis underlying familial hypercalciuria and calcium stone formation remains
      elusive. The molecular basis of other metabolic risk factors such as
      hyperuricosuria, hyperoxaluria and hypocitraturia is being unraveled and is
      allowing new insights into renal stone pathogenesis. CONCLUSION: The discovery of
      both rare and common molecular defects leading to renal stones will hopefully
      increase our understanding of the disease pathogenesis. Such knowledge will allow
      screening for genetic defects and the use of specific drug therapies in order to
      prevent renal stone formation.

PMID- 21071987
TI  - Loop disorders: insights derived from defined genotypes.
AB  - Great progress has been made in the last 15 years in the characterization and the
      pathophysiological understanding of renal salt and water wasting associated with
      inherited disorders of the thick ascending limb (TAL) of Henle's loop, the loop
      disorders. Besides careful clinical observations and innovative physiological
      concepts, molecular genetics have made this progress possible. So far, mutations
      in five different genes may be responsible for the loop disorders. These gene
      products are as follows: NKCC2 symporter, ROMK, ClC-Ka, ClC-Kb, and barttin, a
      beta-subunit to both chloride channels. The key symptoms, such as polyhydramnios
      secondary to fetal polyuria, postnatal volume depletion with hypotension, iso- or
      hyposthenuria, hyperprostaglandinuria and hypercalciuria followed by hypokalemic
      alkalosis secondary to hyperaldosteronism, are typical features of loop disorders
      that are restricted to TAL, such as in disorders with NKCC2 and ROMK mutations.
      However, transient perinatal hyperkalemia in infants with ROMK mutations suggests
      an additional function of ROMK for K secretion in the cortical collecting duct.
      The extremely rare human ClC-Kamutation has only been described in combination
      with ClC-Kb mutations. Similar to barttin mutations, this double knockout of
      transepithelial salt transport in TAL and in distal convoluted tubule (DCT) leads
      to a severe loop disorder with deafness. In contrast, the isolated ClC-Kb
      mutation predominantly appears as an incomplete loop disorder with features
      similar to an isolated DCT defect, because ClC-Kb function in TAL can in part be
      compensated by ClC-Ka. This compensation does not exist in DCT. Besides these
      defined genotypes, the type and the severity of mutation as well as the onset and
      quality of medical care are important determinants for the patients' outcome.
      Considering a few variables, such as transient hyperkalemia, disease onset beyond
      neonatal period, profound hypochloremia and hypokalemia, or congenital hearing
      loss, might be helpful to guide genetic testing efficiently.

PMID- 21071988
TI  - The effect of herpes simplex virus-1 on nitric oxide synthase in the rat brain:
      the role of glucocorticoids.
AB  - OBJECTIVE: Herpes simplex virus-1 (HSV-1) is a common cause of viral encephalitis
      manifested by activation of the adrenocortical axis, fever and behavioral
      changes. We investigated the early effects of HSV-1 on constitutive (c) and
      inducible (i) nitric oxide synthase (NOS) activity in rat brain and in mixed
      glial cell culture. The effect of glucocorticoids (GCs) on NOS responses to HSV-1
      was also determined. METHODS: NOS activity was evaluated by the conversion of 3H
      arginine to 3H-citrulline. Nitrites were measured in supernatants of activated
      glial cells. RESULTS: Under basal conditions, the highest cNOS activity was found
      in the cerebellum, while activity was much lower in the pons and negligible in
      the hypothalamus and hippocampus. Forty-eight hours after intracerebral injection
      of HSV-1, serum corticosterone was increased and NOS activity in the cerebellum
      and pons was inhibited. Adrenalectomy had no effect on the basal NOS activity but
      completely abrogated the inhibitory effect of HSV-1. Administration of the iNOS
      inhibitor aminoguanidine did not significantly change NOS activity, suggesting
      that the activity found in the cerebellum and pons can be attributed to the cNOS
      isoform. In mixed glial cell culture infected with HSV-1 and then activated with
      lipopolysaccharide, NOS activity and nitrite production were inhibited by 77 and
      53%, respectively. CONCLUSIONS: These results suggest that brain NOS activity is
      inhibited in the early stages of HSV-1 infection and requires the presence of
      circulating GCs. HSV-1-induced brain NOS inhibition may play a role in neuronal
      viral invasion and in the activation of the adrenocortical axis.

PMID- 21071989
TI  - Palliative chemotherapy does not improve survival in metastatic esophageal
      cancer.
AB  - BACKGROUND: The role of chemotherapy in metastatic esophageal carcinoma (MEC)
      remains a matter of debate. The aim of this retrospective study was to analyze
      the survival impact of chemotherapy after stratification for prognostic factors.
      METHODS: Consecutive patients with MEC (1995 to 2008) were randomly assigned to a
      development (n = 171) and a validation cohort (n = 113). We had first identified
      prognostic factors using the Kaplan-Meier and Cox methods in the development
      cohort and then validated them in the validation cohort. Then, we analyzed the
      impact of chemotherapy after stratification for these prognostic factors. The
      majority of patients had squamous cell carcinoma (80%). RESULTS: The Cox model
      has retained 2 prognostic factors only: associated cancers (hazard ratio = 2.77,
      range 1.39-5.54, p = 0.004) and grade 3-4 dysphagia (hazard ratio = 1.44, range
      1.08-2.14, p = 0.007). Median survival was 10.9 in patients with 0 (n = 77), 6.2
      in those with 1 (n = 65) and 1.8 months in those with 2 prognostic factors (n =
      11/171; p = 0.025). The median survival times of the patients with 0, 1 and 2
      prognostic factors were 13 versus 9 months (nonsignificant, NS), 6 versus 5
      months (NS) and 5 versus 1.3 months (NS) in patients with and without
      chemotherapy, respectively. CONCLUSION: Our data suggest that chemotherapy has no
      significant effect on survival for unselected MEC patients, regardless of the
      prognostic factors we identified.

PMID- 21071990
TI  - Expression of estrogen receptor beta and phosphorylation of estrogen receptor
      alpha serine 167 correlate with progression-free survival in patients with
      metastatic breast cancer treated with aromatase inhibitors.
AB  - Aromatase inhibitor (AI) is widely used as an endocrine treatment in
      postmenopausal patients with hormone receptor-positive breast cancer. To identify
      useful prognostic factors for patients with metastatic breast cancer treated with
      AI therapy, we investigated the association between several hormone receptor
      related factors and prognosis. The expressions of estrogen receptor-alpha
      (ERalpha), ERbeta, progesterone receptor, the phosphorylation of ERalpha serine
      118 (Ser118) and ERalpha Ser167 were examined using immunohistochemical
      techniques for the primary tumors of 41 patients with metastatic breast cancer
      who received first-line AI therapy after relapse. To assess the associations of
      protein expression and phosphorylation levels with progression-free survival
      (PFS), the levels of each factor were categorized into low and high values at
      optimal cutoff points. In univariate analysis, high ERalpha expression and high
      ERalpha Ser167 phosphorylation correlated with longer PFS (p = 0.016 and 0.013,
      respectively). In multivariate analysis, low ERbeta expression and high ERalpha
      Ser167 phosphorylation correlated with longer PFS (p = 0.031 and 0.004,
      respectively). Patients with both low ERbeta expression and high ERalpha Ser167
      phosphorylation had longer PFS than the others (p = 0.0107). These data suggest
      that the expression of ERbeta and phosphorylation of ERalpha Ser167 may be useful
      prognostic factors in patients with metastatic breast cancer who received first
      line AI therapy.

PMID- 21071991
TI  - Safety and feasibility of using sorafenib in recurrent hepatocellular carcinoma
      after orthotopic liver transplantation.
AB  - BACKGROUND AND AIM: The majority of patients who undergo orthotopic liver
      transplantation (OLT) for hepatocellular carcinoma (HCC) have a very good
      prognosis if the tumor is within the Milan criteria. However, 10-15% of patients
      will have reoccurrence after OLT. Currently, sorafenib is available for advanced
      HCC. The safety and efficacy of sorafenib in this population has not been
      reported. METHODS: We retrospectively looked at 54 patients who received
      sorafenib for advanced HCC. Out of 54 patients, we analyzed 9 who received
      sorafenib after OLT for HCC reoccurrence at Cleveland Clinic. RESULT: The median
      age at the time treatment with sorafenib was initiated was 59 years (range 46
      77). Two patients received prior local therapy. Most of the toxicity was expected
      side effects from sorafenib except in 1 patient who developed hematological
      toxicity. Six patients required dose reduction secondary to toxicity. There were
      no unexpected complications from interaction with immunosuppressive medication.
      One patient achieved complete radiographic remission. Median survival from the
      start of sorafenib had not been reached at the time of writing; however, the 4
      month survival rate is currently estimated to be 84 +/- 15%, and 1 patient with
      lung reoccurrence has been treated for almost 18 months thus far. CONCLUSION:
      Sorafenib can be used in patients with recurrent HCC after liver transplantation
      with tolerable toxicity; however, dose adjustment may be required. A larger
      prospective study is necessary to determine the efficacy of sorafenib in this
      group of patients.

PMID- 21071992
TI  - Stop and go FOLFOX plus bevacizumab chemotherapy in the first-line treatment of
      metastatic colorectal cancer.
AB  - BACKGROUND: Infusional 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) plus
      bevacizumab chemotherapy is commonly implemented in the first-line treatment of
      metastatic colorectal cancer. A stop and go oxaliplatin strategy has been
      recommended to reduce oxaliplatin-associated neuropathy. Despite the acceptance
      of this strategy by community and academic practices, efficacy data with this
      approach are limited. METHODS: We analyzed the efficacy of a stop and go FOLFOX
      regimen combined with bevacizumab in a single institute between January 2007 and
      December 2009. Oxaliplatin was withdrawn electively after 8 cycles of treatment
      and patients were maintained on 5-fluorouracil/leucovorin and bevacizumab until
      progression. When feasible, patients were rechallenged with oxaliplatin upon
      progression. RESULTS: Sixty-seven patients were treated and analyzed for outcome.
      The response rate of this group was 58%. The median progression-free and overall
      survival was 10.6 and 26.7 months, respectively. The median duration of disease
      control in the 18-patient subgroup that was rechallenged with oxaliplatin was
      21.2 months. CONCLUSIONS: Elective withdrawal of oxaliplatin after 8 cycles in
      the setting of FOLFOX and bevacizumab does not appear to compromise the activity
      of this regimen. A stop and go approach of FOLFOX plus bevacizumab is effective
      and may reduce treatment costs and toxicity in comparison with a continuous
      FOLFOX treatment strategy.

PMID- 21071993
TI  - Cisplatin application in pregnancy: first in vivo analysis of 7 patients.
AB  - Cervical cancer in pregnancy is an oncologic challenge. Empirical cisplatin is
      recommended to prevent cancer progression until fetal maturity. Seven patients
      with cervical cancer in the second trimester decided to delay delivery together
      with neoadjuvant chemotherapy. After 2-4 cycles, caesarean section and radical
      hysterectomy were performed above 32 weeks of gestation. Synchronous samples from
      maternal blood, umbilical cord blood and amniotic fluid were taken. All patients
      delivered healthy babies. Cisplatin concentrations in umbilical cord and amniotic
      fluid were 31-65 and 13-42% of the maternal blood, respectively. This is the
      first series on in vivo cisplatin concentration in the fetomaternal compartment.

PMID- 21071994
TI  - Prognostic model to predict outcomes in non-small cell lung cancer patients with
      erlotinib as salvage treatment.
AB  - PURPOSE: To devise a prognostic model based on clinical parameters for non-small
      cell lung cancer (NSCLC) patients treated with erlotinib as a salvage therapy.
      PATIENTS AND METHODS: Between July 2006 and September 2008, two hundred fifty
      seven metastatic/relapsed NSCLC patients who had been treated with erlotinib as a
      salvage therapy were analyzed retrospectively. RESULTS: For the 257 patients, the
      median overall survival (OS) and progression-free survival (PFS) with erlotinib
      treatment were 12.4 and 2.8 months. Multivariate analysis showed that an ECOG
      performance status of 2 or more, an elevated serum LDH level, and the absence of
      skin rash were independent adverse prognostic factors for OS and that the
      presence of intra-abdominal metastasis, 2 or more prior chemotherapy regimens,
      and the absence of skin rash were prognostic factors for PFS. Patients were
      categorized into the following 4 prognosis groups on the basis of each adverse
      prognostic factor: good, intermediate, poor, and very poor prognosis. The median
      OS times for the good, intermediate, poor, and very poor prognosis groups were
      22.0, 9.3, 5.4, and 2.7 months (p < 0.001) and the median PFS times were 6.5,
      3.0, 1.2, and 0.9 months (p < 0.001). CONCLUSION: This prognostic model based on
      clinical parameters would be useful to identify patients who might be most likely
      to benefit from erlotinib therapy in clinical practice.

PMID- 21071995
TI  - Sunitinib in patients with advanced hepatocellular carcinoma after progression
      under sorafenib treatment.
AB  - OBJECTIVE: To evaluate the safety and efficacy of sunitinib in patients with
      advanced hepatocellular carcinoma (HCC) after progression under sorafenib
      treatment. METHODS: Sunitinib was administered at 37.5 mg daily (4-weeks-on/2
      weeks-off schedule) after progression under sorafenib treatment. Adverse events
      (AEs) were assessed using NCI-CTCAE v3.0, and tumor response was evaluated
      according to RECIST. Data were analyzed retrospectively. RESULTS: Eleven patients
      with metastatic disease were treated. Seven patients (64%) presented with no
      liver cirrhosis, including 3 patients with a history of liver transplantation.
      The first radiological follow-up showed stable disease in 40% of patients after
      marked radiological progression under sorafenib. The median time to progression
      was 3.2 months. Treatment was discontinued due to radiological progression (n =
      9) or AEs (n = 2; hemorrhages) in all patients after 3.5 months. The median
      overall survival was 8.4 months. All patients with Child-Pugh class B liver
      cirrhosis suffered a clinical deterioration of liver function and died within 4
      months due to tumor progression. CONCLUSIONS: Sunitinib provided modest antitumor
      activity in patients with advanced HCC after progression under sorafenib
      treatment. Patients with Child-Pugh class B liver cirrhosis might not receive a
      clinical benefit from this second-line approach. Hemorrhagic complications may
      represent a clinically relevant problem of sunitinib in patients with advanced
      HCC.

PMID- 21071996
TI  - Early markers of choroidal neovascularization in the fellow eye of patients with
      unilateral exudative age-related macular degeneration.
AB  - OBJECTIVE: To identify morphological and/or functional early markers of choroidal
      neovascularization (CNV) development in fellow eyes of patients with exudative
      age-related macular degeneration (AMD). DESIGN: This is a single-center,
      prospective, observational, longitudinal 2-year study. PATIENTS: Patients were
      enrolled with the diagnosis of neovascular AMD in 1 eye and early age-related
      maculopathy (ARM) in the fellow eye. Intervention or Methods: All patients
      completed the baseline assessment and were followed up for up to 24 months with
      repeated ophthalmic and imaging assessments performed at 6-month intervals. MAIN
      OUTCOME MEASURES: Each patient underwent a detailed ocular and medical history, a
      complete ophthalmologic examination with color fundus photography, fluorescein
      angiography, indocyanine green angiography (ICG), optical coherence tomography
      (OCT), fundus autofluorescence (FAF) imaging and retinal leakage analysis (RLA).
      RESULTS: Sixty-two patients were enrolled in the study. Large or intermediate
      drusen were present in 100% of the study eyes and hyperpigmentation in 46% (24
      eyes). Fifty-two patients completed the 2-year study follow-up. Large soft drusen
      (>125 MUm) were observed in 15 out of 17 eyes (88%) that converted and developed
      CNV during the study and in 25 out of 35 eyes (71.4%) that did not develop CNV.
      Among the 17 eyes that developed CNV, 9 (53%) showed abnormal findings before
      conversion, on ICG. No particular FAF pattern was found to be correlated with
      conversion to wet AMD. OCT was able to document the presence of intra- or
      subretinal fluid at the time of conversion in all 17 eyes that developed CNV
      during the study. Alterations of the blood-retinal barrier were identified by RLA
      before conversion in 76% of the eyes that converted and 23% of the eyes that did
      not convert during the study. CONCLUSIONS: Characterization of early ARM
      phenotypes is challenging. By combining different imaging modalities of the
      macula and correlating this information, we were able to determine the presence
      of functional macular alterations in the fellow eye of patients with this disease
      before development of CNV.

PMID- 21071997
TI  - Disposition and metabolism of ralfinamide, a novel Na-channel blocker, in healthy
      male volunteers.
AB  - Ralfinamide is an alpha-aminoamide derivative with ion channel blocking
      properties, acting both peripherally and centrally through different molecular
      targets important in pain control. Absorption, blood and plasma time courses, and
      urinary and faecal excretion of total radioactivity were assessed in 6 male
      healthy volunteers administered a single oral dose of 320 mg 14C-(S)-ralfinamide.
      Pharmacokinetics of the parent drug were investigated over 120 h, urinary and
      plasma metabolites up to 192 h post-dose. 14C-(S)-ralfinamide was rapidly and
      completely absorbed. Ralfinamide and the dealkylated ralfinamide metabolite (NW
      1716) represented the majority of plasma radioactivity. Plasma elimination of the
      parent compound occurred mono-exponentially (half-life approx. 15 h). 14C
      radioactivity was eliminated in a bi-phasic manner (terminal half-life of 60 and
      24 h for plasma and whole blood, respectively). Plasma-concentrations of
      unchanged ralfinamide were significantly lower than radioactivity concentrations,
      indicating metabolism of the parent compound. At 192 h post-dose the total
      balance of radioactivity was almost complete (95%). The main route of excretion
      was via the kidneys (94% of the dose). Major metabolites identified in urine and
      plasma were the N-dealkylated acid of ralfinamide and deaminated ralfinamide acid
      (NW-1799). Other metabolites, in particular the product of glucuronide
      conjugation N-dealkylated-beta-glucuronide, were identified.

PMID- 21071998
TI  - Liver X receptor agonist methyl-3beta-hydroxy-5alpha,6alpha-epoxycholanate
      attenuates atherosclerosis in apolipoprotein E knockout mice without increasing
      plasma triglyceride.
AB  - BACKGROUND: Liver X receptors (LXRs) promote macrophage reverse cholesterol
      transport and cholesterol excretion from the body. The synthetic LXR ligands
      T0901317 and GW3965 were shown to significantly inhibit atherosclerosis in mice
      and to increase the expression of ATP-binding cassette transporter A1 (ABCA1) in
      the atherosclerotic lesions. However, these compounds increase plasma and hepatic
      triglyceride (TG) levels in mice. Methyl-3beta-hydroxy-5alpha,6alpha
      epoxycholanate (MHEC), synthesized from hyodeoxycholic acid, functions as an LXR
      agonist, but its role in atherogenesis and lipid metabolism remained to be
      elucidated. METHODS: THP-1-derived macrophages were cultured in the medium con-
      taining various concentrations of MHEC or T0901317 (0-10 MUmol/l) for 24 h.
      Reverse transcription polymerase chain reaction was used to quantify LXRalpha,
      LXRbeta and ABCA1 mRNA levels in macrophages. Additionally, MHEC or T0901317 was
      orally administered at 10 mg/kg daily for 6 weeks in apolipoprotein E knockout
      (apoE-/-) mice fed a high-cholesterol diet. Plasma lipids were determined
      enzymatically. The area of and ABCA1 expression in the aortic atherosclerotic
      lesions were measured by oil red O staining and immunohistochemistry,
      respectively. RESULTS: Both MHEC and T0901317 equally stimulated LXRalpha and
      ABCA1 mRNA expression in a dose-dependent manner in THP-1-derived macrophages,
      but they did not induce LXRbeta mRNA expression significantly. The plasma levels
      of total cholesterol, TG and high-density lipoprotein cholesterol were
      significantly higher in T0901317-treated mice than in the vehicle-treated control
      group. Interestingly, MHEC treatment dramatically increased plasma high-density
      lipoprotein cholesterol without altering plasma levels of total cholesterol and
      TG. Both MHEC and T0901317 equally inhibited the development of atherosclerotic
      lesions in apoE-/- mice. The expression of ABCA1, a cholesterol efflux
      transporter, was greatly induced by the two LXR agonists in the artery wall.
      CONCLUSIONS: MHEC is a novel LXR agonist and it inhibits atherosclerosis in apoE
      /- mice without raising blood TG. Thus, MHEC relative to T0901317 may be a better
      therapeutic LXR agonist for the treatment of atherosclerosis.

PMID- 21071999
TI  - Pifithrin-alpha, an inhibitor of p53 transactivation, up-regulates COX-2
      expression through an MAPK-dependent pathway.
AB  - Cyclooxygenase-2 (COX-2) has been reported to be elevated in many cancers,
      including breast and colorectal cancers, resulting in accumulation of
      prostaglandin E2 in the cancer cell environment. In this study, we investigated
      the effect of pifithrin (PFT)-alpha, an inhibitor of p53 transactivation, on COX
      2 expression in breast and fibrosarcoma cells. Our results showed that COX-2
      expression was dose-dependently increased by PFT-alpha in MDA-MB231 breast cancer
      cells with mutant p53. In addition, the expression level of COX-2 was also
      increased by PFT-alpha in normal fibroblasts as well as in HT1080 fibrosarcoma
      cells with p53 wild-type cells. To verify the regulatory mechanism of COX-2 in
      response to PFT-alpha, we pretreated cells with a mitogen-activated protein
      kinase (MAPK) kinase (MEK)1/2 inhibitor (UO126) and a phosphoinositide-3 (PI-3K)
      inhibitor (LY294002). PFT-alpha-induced COX-2 expression was significantly
      decreased by UO126 and LY294002 in MDA-MB231 cells. However, the phosphorylation
      of extracellular signal-regulated kinase (ERK) was increased by PFT-alpha, but
      not Akt phosphorylation. Finally, we confirmed the correlation of the MEK and PI
      3K pathway and COX-2 expression using the constitutively active (CA)-MEK and myr
      Akt adenovirus systems. COX-2 expression was increased by CA-MEK transfection,
      but not by myr-Akt. Taken together, we have demonstrated that PFT-alpha-induced
      COX-2 expression is regulated through a MEK/ERK pathway in MDA-MB231 human breast
      cancer cells.

PMID- 21072000
TI  - Psychometric validity of the strengths and difficulties questionnaire
      dysregulation profile.
AB  - BACKGROUND: In many severely mentally disordered children, the clinical
      presentation is complicated by comorbid affective and behavioral dysregulation.
      Recently, a highly heritable behavioral phenotype of simultaneous deviance on the
      anxious/depressed, attention problems, and aggressive behavior syndrome scales
      has been identified on the Child Behavior Checklist Dysregulation Profile (CBCL
      DP). The aim of the present pilot study was to determine an equivalent to the
      CBCL-DP using the Strengths and Difficulties Questionnaire (SDQ). SAMPLING AND
      METHODS: We applied stepwise linear discriminant analyses and receiver operating
      characteristic (ROC) analysis to data from 543 consecutively referred children
      and adolescents, aged 5-17 years. The CBCL and the SDQ were completed by parents
      as part of the diagnostic routine. ICD-10 discharge diagnoses were established in
      consensus conferences. RESULTS: A combination of five SDQ items (SDQ
      Dysregulation Profile, SDQ-DP) yielded the best discrimination of children with
      and without CBCL-DP and classified 81.0% of the subjects correctly leading to an
      area under the curve of 0.93. The content of the five SDQ-DP items mirrors well
      the mixed behavioral phenotype of anxious-depressive, aggressive and attention
      problems captured by the CBCL-DP. SDQ-DP status was highly correlated with CBCL
      DP status and was best defined by a SDQ-DP score >=5. CONCLUSIONS: The
      psychometric properties of the SDQ-DP have been robustly tested and validated.
      Based on these results, clinicians may use the SDQ-DP as a useful and economical
      screening measure to improve the assessment, prevention, and treatment of severe
      dysregulation in childhood and adolescence. Future investigations should study
      the longitudinal stability, heritability, and genetic associations of this
      behavioral phenotype.

PMID- 21072001
TI  - Prenatal stress: course and interrelation of emotional and physiological stress
      measures.
AB  - BACKGROUND: Prenatal stress is known to be a potential risk factor for cognitive,
      behavioural and motor development that even last until adolescence. A consensus
      of how 'prenatal stress' can be measured, in which trimester of pregnancy women
      should be studied and whether subjective feelings of being stressed are
      associated with a hormonal response is still lacking. To close this gap, a
      prospective longitudinal study was conducted in pregnant women. SAMPLING AND
      METHODS: 108 subjects were asked to fill out questionnaires concerning pregnancy
      related anxiety, perceived stress, marital satisfaction, critical life events and
      to collect salivary cortisol in each trimester of pregnancy. RESULTS: Fear of
      giving birth increases until the end of pregnancy, and marital satisfaction is
      highest at the end of pregnancy. Perceived stress is related to a hormonal
      response in cortisol only in the first (r = 0.18, p < 0.10) and second (r = 0.18,
      p < 0.10) trimesters of pregnancy. Critical life events are linked to raised
      cortisol levels in early pregnancy only (r = 0.28, p < 0.01). CONCLUSION:
      Prenatal stress can be operationalized by using different subjective as well as
      physiological stress measures. Only in the first half of pregnancy self-report
      and physiological stress measures seem to be associated.

PMID- 21072002
TI  - Standardized rater training for the Hamilton Depression Rating Scale (HAMD17) and
      the Inventory of Depressive Symptoms (IDS(C30)).

PMID- 21072003
TI  - Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL
      2 human melanoma cells.
AB  - In this study, we have shown that gene expression of human GD3 synthase (hST8Sia
      I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To
      elucidate the mechanism underlying the downregulation of hST8Sia I gene
      expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible
      promoter region within the hST8Sia I gene using luciferase constructs carrying 5'
      deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking
      region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which
      contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and
      NF-kappaB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2
      cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kappaB
      binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I
      in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I
      gene expression through NF-kappaB activation in human melanoma cells.

PMID- 21072005
TI  - Why does wound care remain a low priority?

PMID- 21072004
TI  - Novel deletion of the E3A ubiquitin protein ligase gene detected by multiplex
      ligation-dependent probe amplification in a patient with Angelman syndrome.
AB  - Angelman syndrome (AS) is a severe neurobehavioural disorder caused by failure of
      expression of the maternal copy of the imprinted domain located on 15q11-q13.
      There are different mechanisms leading to AS: maternal microdeletion, uniparental
      disomy, defects in a putative imprinting centre, mutations of the E3 ubiquitin
      protein ligase (UBE3A) gene. However, some of suspected cases of AS are still
      scored negative to all the latter mutations. Recently, it has been shown that a
      proportion of negative cases bear large deletions overlapping one or more exons
      of the UBE3A gene. These deletions are difficult to detect by conventional gene
      scanning methods due to the masking effect by the non-deleted allele. In this
      study, we have used for the first time multiplex ligation-dependent probe
      amplification (MLPA) and comparative multiplex dosage analysis (CMDA) to search
      for large deletions affecting the UBE3A gene. Using this approach, we identified
      a novel causative deletion involving exon 8 in an affected sibling. Based on our
      results, we propose the use of MLPA as a fast, accurate and inexpensive test to
      detect large deletions in the UBE3A gene in a small but significant percentage of
      AS patients.

PMID- 21072006
TI  - Managing wound pain during application and removal of dressings.

PMID- 21072007
TI  - Effects of education and experience on nurses' value of ulcer prevention.
AB  - Few studies have focused on the value that nurses place on pressure ulcer
      prevention, even though values are a key determinant of a person's behaviour and
      actions. Previous studies have reported that the value that a nurse places on
      pressure ulcer prevention is linked to the skin care that they deliver. This
      article describes a study that was undertaken to determine the value that nurses
      place on pressure ulcer prevention, which also identified how this value is
      formed. The participants in this study (n=16), were recruited from non-acute
      adult medical wards of 14 hospitals in one NHS trust, and a university. Data was
      gathered via semi-structured interviews and interpreted through Straussian
      grounded theory. The findings of this study show how the participants underwent a
      transition from placing a low to a high value on pressure ulcer prevention and
      how this affected patient care. The key point in this transition appears to be an
      encounter with a patient with a high grade pressure ulcer, which caused the
      nurses to reappraise their values. Looking after patients with pressure ulcers
      seems to increase the value that a nurse places on pressure ulcer prevention. The
      education that nurses receive on pressure ulcer prevention only appears to alter
      their values when they have some experience of looking after patients with
      pressure ulcers.

PMID- 21072008
TI  - Sternal wound infections: improvements made to reduce rates.
AB  - Wound infections from surgical sites account for 15% of all healthcare-associated
      infections (National Institute for Health and Clinical Excellence (NICE), 2008).
      There is evidence that the care provided before and after the operation is
      paramount to minimize the risk of surgical site infection. Sternal wound
      infections lengthen hospital stays (or prompt readmission) and carry a high
      mortality rate. In August 2009 a Manchester Hospital discovered a cluster of
      three patients with sternal wound infections. A review of clinical data for
      patients having cardiac surgery from 1 December 2008 and 9 October 2009 revealed
      an increased incidence of patients with sternal wound infections. The data did
      not reveal a significant problem, but one that should be kept under observation.
      During the investigation no single pathogen had been identified as responsible
      and no obvious source of environmental infection was identified. Implementing
      additional infection prevention and control practices helped the hospital team to
      improve the care given to patients. A host of factors, ranging from providing
      more information on wound care to patients, improving audit scores, and adhering
      to NICE guidelines, contributed to the reduction in this type of surgical site
      infection.

PMID- 21072009
TI  - Exudate, infection and patient quality of life.
AB  - Efficient and cost-effective management of excessive wound exudate continues to
      present unique challenges to nurses. Accurate patient and wound assessment is
      essential to inform the treatment and selection of suitable dressings. The wide
      range of modern wound management products should be sufficient to meet the needs
      of every wound type at all phases of healing, and as circumstances change.
      However, there are still situations in which nurses are having to change
      dressings a number of times in 24 hours to prevent maceration (i.e. the softening
      and whitening of skin that is kept constantly wet), soiling, and the potential
      for cross-infection. There is no easy solution to the problem, but as nurses
      become more knowledgeable about identifying and managing the causes of excessive
      exudate, the available management options, and, as dressing materials become more
      sophisticated, practice should improve in this area.

PMID- 21072010
TI  - Patients' views on topical negative pressure: 'effective but smelly'.
AB  - Topical negative pressure (TNP) is increasingly being used in both the UK and
      internationally, on wounds of acute, chronic and surgical origin. However, little
      is known about patients' experiences of this therapy. NHS Quality Improvement
      Scotland undertook a health technology assessment on TNP in 2009-2010. This
      assessment considered clinical and cost-effectiveness, patient issues, and
      organizational issues. This article describes the primary research undertaken for
      the patient issues section. Qualitative methods were used to attempt to
      understand patients' perceptions and experiences of TNP. A focus group and
      individual interviews were held in Glasgow, recorded, and transcribed verbatim.
      Data were analysed thematically. The themes which emerged as being important to
      patients receiving TNP were healing, smell, embarrassment, pain, nurse training,
      self-care, information provision, getting out of hospital, and returning to
      normal life. Implications for practice are suggested for manufacturers, service
      leads and nurses.

PMID- 21072011
TI  - Barrier dressings in surgical site infection prevention strategies.
AB  - Healthcare-associated infections (HCAIs) are a matter of priority for the NHS.
      They are associated with significant morbidity, and frequently lead to increased
      length of hospital stay, pain and discomfort for the patient, and in some cases
      even permanent disability. It is estimated that surgical site infections (SSIs)
      constitute around 14% of all HCAIs. Any break in the skin affords a portal of
      entry for microbial pathogens, and hence places the patient at an increased risk
      of infection. To address the issue, a multi-factorial strategy for the prevention
      of SSIs is essential, with postoperative dressings playing a key part alongside
      universal precautions such as hand hygiene and aseptic technique. The available
      guidance specifies the need for a postoperative dressing which provides an
      effective physical barrier and a moist environment for optimal wound healing.
      Vapour-permeable barrier dressings appear to be effective in meeting both of
      these criteria and also offer additional advantages both to patients and
      practitioners, such as patient comfort and the ability to stay in place whilst
      the patient showers. However, regular wound assessment must be carried out to
      ensure the vapour-permeable postoperative dressing is the right choice for a
      specific patient at a given time.

PMID- 21072012
TI  - Managing wound pain: is there an 'ideal dressing'?

PMID- 21072013
TI  - Does home haemodialysis produce better outcomes for patients?
AB  - Demand for renal replacement therapy (dialysis and transplantation) is projected
      to rise by approximately 5% every year until at least 2030. Therefore, particular
      attention should be paid to areas in which significant increases in demand are
      likely to lead to further pressure on services. There is evidence to support
      higher patient survival rates in home haemodialysis compared with those that
      receive hospital- or satellite-based haemodialysis (i.e. a smaller renal unit
      based in a community hospital closer to the patient's home). Furthermore, studies
      suggest that home haemodialysis is at least as effective as and less costly than
      hospital or satellite unit haemodialysis. Therefore, there is a greater
      requirement for expanding the provision of home haemodialysis, and to make this
      treatment option available to a wider range of patients.

PMID- 21072014
TI  - Managing anaemia of chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a multi-faceted disease which has a number of
      associated complications. Anaemia is one of the most common complications that
      develops early in the course of the disease process. It is associated with
      increased mortality, increased hospitalization rates, and reduced quality of
      life. Low haemoglobin levels may increase risk for progression of CKD,
      cardiovascular morbidity and mortality. This article aims to address the
      importance of early recognition and management of anaemia in CKD, and the role of
      the health professional in this regard. Issues that will be discussed include
      causes, screening, guidelines, current research and recommended treatments of
      anaemia in CKD, along with recommendations for future practice in this pivotal
      area of renal care.

PMID- 21072015
TI  - Glaucoma expert patient programme and ocular hypotensive treatment.
AB  - Expert patient programmes (EPPs) are becoming an increasingly important aspect of
      chronic disease management, resulting in improved health outcomes for patients.
      Patients with chronic open angle glaucoma (COAG) require lifelong therapy.
      However, to date, no EPPs have been designed specifically for patients with
      chronic eye conditions like COAG. This article describes the development and
      implementation of the Glaucoma Expert Patient Programme (GEPP), a glaucoma
      specific educational self-management programme which aims to improve glaucoma
      patients' knowledge, self-management skills, expectations and adherence to
      treatment. A review of theoretical frameworks and models which underpin the
      design, use and conduct of EPPs was undertaken, and the GEPP was designed based
      on the model by Kate Lorig (2003). The result is an educational programme which
      offers COAG patients a different perspective on their condition and supports them
      with knowledge, skills and strategies to better manage their condition on a daily
      basis.

PMID- 21072016
TI  - Using competences and competence tools in workforce development.
AB  - The NHS Knowledge and Skills Framework (KSF) has been a driving force in the move
      to competence-based workforce development in the NHS. Skills for Health has
      developed national workforce competences that aim to improve behavioural
      performance, and in turn increase productivity. This article describes five
      projects established to test Skills for Health national workforce competences,
      electronic tools and products in different settings in the NHS. Competences and
      competence tools were used to redesign services, develop job roles, identify
      skills gaps and develop learning programmes. Reported benefits of the projects
      included increased clarity and a structured, consistent and standardized approach
      to workforce development. Findings from the evaluation of the tools were positive
      in terms of their overall usefulness and provision of related training/support.
      Reported constraints of using the competences and tools included issues relating
      to their availability, content and organization. It is recognized that a highly
      skilled and flexible workforce is important to the delivery of high-quality
      health care. These projects suggest that Skills for Health competences can be
      used as a 'common currency' in workforce development in the UK health sector.
      This would support the need to adapt rapidly to changing service needs.

PMID- 21072017
TI  - Are international nursing students disadvantaged by UK patients?
AB  - International students bring billions of pounds annually to the UK through higher
      education. Although nursing students may not contribute as significantly in
      monetary terms as traditional graduate and postgraduate learners, they do,
      however, bring with them other benefits in terms of wealth of experience,
      diversity and cultural capital, often looking after client groups sometimes
      marginalized by mainstream society. The reality is that many nursing homes and
      care homes simply would not function without internationally recruited nurses
      contributing to our health service and the wellbeing of society. The author of
      this article is a module manager for a Nursing and Midwifery Council regulated
      Overseas Nurses Programme, which runs up to four times per year at a large
      Faculty of Health, Sports and Science in South Wales. Anecdotal evidence from
      class disclosures by international nursing students provided the rationale for
      this independent enquiry. Listening to verbal accounts suggested that
      internationally-recruited nurses were experiencing episodes of 'unfair treatment'
      by patients under their care when undertaking the clinical practice component of
      the programme.

PMID- 21072018
TI  - Making patient safety work: the Health Foundation snapshot.
AB  - John Tingle discusses two recent publications from The Health Foundation charity
      which showcases their current patient safety work.

PMID- 21072019
TI  - NMC launches new standards for undergraduate nurse programmes.
AB  - As the nursing profession moves towards an all-graduate workforce, Professor Alan
      Glasper discusses the recently announced standards and structure of these
      educational programmes.

PMID- 21072021
TI  - Sleep: the nursing implications.

PMID- 21072022
TI  - Acute oral toxicity and brine shrimp lethality of Elaeis guineensis Jacq., (oil
      palm leaf) methanol extract.
AB  - Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine
      for treating various ailments. An evaluation on the toxicity of extracts of this
      plant is crucial to support the therapeutic claims. The acute oral toxicity and
      brine shrimp lethality of a methanolic extract of this plant was tested. Oral
      administration of crude extract at the highest dose of 5,000 mg/kg resulted in no
      mortalities or evidence of adverse effects, implying that E. guineensis is
      nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs
      confirm this evidence. The E. guineensis extracts screened for toxicity against
      brine shrimp had 50% lethal concentration (LC50) values of more than 1.0 mg/mL
      (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract
      was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the
      least mortalities happened to be at 0.195 mg/mL concentration. The results of
      both tests confirm that E. guineensis is nontoxic and hence safe for commercial
      utilization.

PMID- 21072025
TI  - 2-chlorophenyl zinc bromide: a convenient nucleophile for the mannich-related
      multicomponent synthesis of clopidogrel and ticlopidine.
AB  - A methodological study devoted to the Mannich-like multicomponent synthesis of
      the antiplatelet agent (+/-)-clopidogrel (7) and the ethyl ester analogue 6 is
      described. The process involves the formation of 2-chlorophenyl zinc bromide (2)
      and its subsequent reaction with an alkyl glyoxylate and 4,5,6,7
      tetrahydrothieno[3,2-c]pyridine (3). We demonstrate that the organozinc reagent 2
      also constitutes a very convenient nucleophile for the multicomponent synthesis
      of the benzylamine core of ticlopidine (9).

PMID- 21072023
TI  - Investigating the spectrum of biological activity of ring-substituted
      salicylanilides and carbamoylphenylcarbamates.
AB  - In this study, a series of twelve ring-substituted salicylanilides and
      carbamoylphenylcarbamates were prepared and characterized. The compounds were
      analyzed using RP-HPLC to determine lipophilicity. They were tested for their
      activity related to the inhibition of photosynthetic electron transport (PET) in
      spinach (Spinacia oleracea L.) chloroplasts. Moreover, their site of action in
      the photosynthetic apparatus was determined. Primary in vitro screening of the
      synthesized compounds was also performed against mycobacterial, bacterial and
      fungal strains. Several compounds showed biological activity comparable with or
      higher than the standards 3-(3,4-dichlorophenyl)-1,1-dimethylurea, isoniazid,
      penicillin G, ciprofloxacin or fluconazole. The most active compounds showed
      minimal anti-proliferative activity against human cells in culture, indicating
      they would have low cytotoxicity. For all compounds, the relationships between
      lipophilicity and the chemical structure are discussed.

PMID- 21072026
TI  - Oligomerization of 3,5-dimethyl benzyl alcohol promoted by clay: experimental and
      theoretical study.
AB  - Linear oligomerization of 3,5-dimethyl benzyl alcohol is induced by a
      montmorillonite clay (Tonsil Optimum Extra), producing 1,3,5,7-tetramethyl-9,10
      dihydro-anthracene, which, by loss of protons results in the product 1,3,5,7
      tetramethylanthracene. It was also found that the compounds 4-(3',5'
      dimethylbenzyl)-1,3,5,7-tetramethyl-9,10-dihydroanthracece and 4-(3',5'
      dimethylbenzyl)-1,3,5,7-tetra-methylanthracene were formed from 1,3,5,7
      tetramethyl-9,10-dihydroanthracene. 1,3,5,7-Tetramethylanthryl radical cation was
      formed from 1,3,5,7-tetramethyl-9,10-dihydroanthracene; it was characterized by
      Electronic Paramagnetic Resonance (EPR). On the other hand, a theoretical
      analysis was performed, allowing the rationalization of the observed products and
      some of the key reaction steps.

PMID- 21072027
TI  - 5,6-Didehydroginsenosides from the roots of Panax notoginseng.
AB  - Two minor novel dammarane-type saponins - 5,6-didehydroginsenoside Rd (1) and 5,6
      didehydroginsenoside Rb1 (2) - were isolated from the dried roots of Panax
      notoginseng along with sixteen known saponins. The structures of the new
      compounds were elucidated on the basis of spectroscopic and chemical methods.

PMID- 21072040
TI  - Documenting the NICU design dilemma: comparative patient progress in open-ward
      and single family room units.
AB  - OBJECTIVE: To test the efficacy of single family room (SFR) neonatal intensive
      care unit (NICU) designs, questions regarding patient medical progress and
      relative patient safety were explored. Addressing these questions would be of
      value to hospital staff, administrators and designers alike. STUDY DESIGN: This
      prospective study documented, by means of Institution Review Board-approved
      protocols, the progress of patients in two contrasting NICU designs. Noise
      levels, illumination and air quality measurements were included to define the two
      NICU physical environments. RESULT: Infants in the SFR unit had fewer apneic
      events, reduced nosocomial sepsis and mortality, as well as earlier transitions
      to enteral nutrition. More mothers sustained stage III lactation, and more
      infants were discharged breastfeeding in the SFR. CONCLUSION: This study showed
      the SFR to be more conducive to family-centered care, and to enhance infant
      medical progress and breastfeeding success over that of an open ward.

PMID- 21072041
TI  - Antepartum eclampsia <34 weeks case series: advisable to postpone delivery to
      administer corticosteroids for fetal pulmonary benefit?
AB  - OBJECTIVE: To determine if postponement of delivery to administer fetal lung
      maturation corticosteroids (PDACs) in mothers with antepartum eclampsia <34 weeks
      gestation benefits the fetus without compromising the mother. STUDY DESIGN: A
      case series of 37 maternal-perinatal pairs over a 9-year period with antepartum
      eclampsia between 24 and 34 weeks gestation from a single tertiary center were
      reviewed retrospectively. Duration of PDAC, clinical course and maternal-fetal
      outcomes, including impact of duration of PDAC on neonatal pulmonary function,
      were recorded for each case. Group assignment was based on length of
      corticosteroid treatment course before delivery: Group A, 0 to <= 24 h, n=28; B,
      24 to <48 h, n=5; C, >= 48 h, n=4. Data were collected and analyzed by one-way
      analysis of variance (ANOVA), ANOVA on ranks, chi(2)-test and Fisher's exact
      tests where appropriate; statistical significance was determined by a P-value
      <0.05. RESULT: Overall, 37 of 68 eclampsia patients in 1999 to 2007 met inclusion
      criteria. No adverse maternal or fetal event occurred while delivery was
      postponed. Immediate neonatal intubation or continuous positive airway pressure
      was required for 23/28 in A, 4/5 in B and 2/4 in C; room air was sufficient at
      birth for 5/28 in A, 1/5 in B and 2/4 in C. No newborn >33 weeks gestation
      required INI. Prolonged (that is, >1 day) mechanical ventilation was not required
      for any infant with a gestational age >= 32 weeks or PDAC >= 48 h. Two of three
      neonatal deaths in group A were attributed to pulmonary insufficiency.
      CONCLUSION: PDAC for antepartum preterm eclampsia, especially <= 32 weeks
      gestation, appears to offer notable fetal pulmonary benefit without significantly
      increasing maternal or fetal risk.

PMID- 21072042
TI  - Monosomal karyotype in myelodysplastic syndromes, with or without monosomy 7 or
      5, is prognostically worse than an otherwise complex karyotype.
AB  - Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal
      monosomies or a single monosomy associated with a structural abnormality. In
      acute myeloid leukemia, MK has been shown to be prognostically worse than an
      otherwise complex karyotype. The current study examines whether the same holds
      true for myelodysplastic syndromes (MDS). A total of 127 MDS patients (median age
      70 years) with a complex karyotype were considered; 106 (83%) met the above
      stipulated criteria for MK and 21 (17%) had a complex karyotype without
      monosomies. Survival was significantly inferior in patients with MK compared with
      those with a complex karyotype without monosomies (P=0.01; HR 1.9, 95% confidence
      interval (95% CI), 1.1-3.3). Multivariable analysis identified MK (P=0.002),
      advanced age (P=0.0004) and bone marrow blast percentage (0.04) as independent
      risk factors for survival. There was no difference in survival among MK patients
      further substratified by the presence or absence of monosomy 7 and/or monosomy 5.
      Although not statistically significant, leukemia-free survival was also worse
      with MK compared with complex karyotype without monosomies (P=0.09; HR 2.7, 95%
      CI 0.8-9.0). MK in MDS identifies a prognostically worse subgroup of patients
      with a complex karyotype, regardless of whether monosomy 7 or 5 is part of the MK
      component.

PMID- 21072044
TI  - The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize
      hematopoietic progenitors.
AB  - The oncogenic fusion protein E2A-HLF is a chimeric transcription factor that
      arises from the t(17;19) translocation in childhood B-cell acute lymphoblastic
      leukemias (B-precursor ALL) and is associated with very poor outcome. We show
      that retroviral-mediated expression of E2A-HLF alone is sufficient to immortalize
      primary lymphoid progenitors. We identify Lmo2 and Bcl-2 as direct target genes
      downstream of E2A-HLF. We use real-time PCR analysis to show that LMO2 and BCL-2
      expression is preferentially upregulated both in biopsy material from t(17;19) B
      precursor ALL patients and lymphoid cell lines derived from t(17;19) leukemias.
      Co-expression of Lmo2 and Bcl-2 was sufficient to immortalize lymphoid progenitor
      cells resulting in a similar phenotype to that induced by E2A-HLF alone. Both
      shRNA-mediated knockdown of Lmo2 expression and pharmacological inhibition of BCL
      2 function in E2A-HLF immortalized cells severely compromised their viability.
      These data suggest that both Lmo2 and Bcl-2 are required for the action of E2A
      HLF in leukemogenesis.

PMID- 21072043
TI  - Inhibition of Grb2 expression demonstrates an important role in BCR-ABL-mediated
      MAPK activation and transformation of primary human hematopoietic cells.
AB  - Chronic myeloid leukemia (CML) results from the expression of the BCR/ABL
      oncogene in a primitive hematopoietic cell. However, BCR/ABL-activated signaling
      mechanisms are dependent on the cellular context in which it is expressed, and
      mechanisms underlying primitive human hematopoietic cell transformation by BCR
      ABL are not well understood. Our previous studies have shown that BCR/ABL-Y177
      has an essential role in Ras activation and human hematopoietic progenitor
      transformation in CML. The adapter protein growth factor receptor-binding protein
      2 (Grb2) can bind phosphorylated BCR/ABL-Y177, induce Grb2-SoS complex formation
      and activate Ras signaling. We investigated the role of Grb2 in CML progenitor
      transformation by cotransducing human CD34+ cells with lentivirus vectors
      expressing short hairpin RNA to Grb2 and retrovirus vectors expressing BCR/ABL.
      We show that Grb2 knockdown significantly inhibits proliferation and survival of
      BCR-ABL-expressing CD34+ cells, but not control CD34+ cells. Grb2 knockdown
      reduced mitogen-activated protein kinase (MAPK) activity in BCR-ABL-expressing
      hematopoietic cells. We conclude that inhibition of Grb2 expression demonstrates
      an important role in BCR-ABL-mediated MAPK activation and transformation of
      primary human hematopoietic cells.These results support further investigation of
      downstream effectors of Grb2-mediated signals and targeting of Grb2 interactions
      in the treatment of CML.

PMID- 21072045
TI  - A genome-wide approach identifies that the aspartate metabolism pathway
      contributes to asparaginase sensitivity.
AB  - Asparaginase is an important component for treatment of childhood acute
      lymphoblastic leukemia (ALL). The basis for interindividual differences in
      asparaginase sensitivity remains unclear. To comprehensively identify genetic
      variants important in the cytotoxicity of asparaginase, we used a genome-wide
      association approach using the HapMap lymphoblastoid cell lines (87 CEU trio
      members) and 54 primary ALL leukemic blast samples at diagnosis. Asparaginase
      sensitivity was assessed as the drug concentration necessary to inhibit 50% of
      growth (inhibitory concentration (IC)(50)). In CEU lines, we tested 2,390,203
      single-nucleotide polymorphism (SNP) genotypes at the individual SNP (P<0.001)
      and gene level (P<0.05), and identified 329 SNPs representing 94 genes that were
      associated with asparaginase IC(50). The aspartate metabolism pathway was the
      most overrepresented among 199 pathways evaluated (P=8.1 * 10(-3)), with primary
      involvement of adenylosuccinate lyase and aspartyl-tRNA synthetase genes. We
      validated that SNPs in the aspartate metabolism pathway were also associated with
      asparaginase sensitivity in primary ALL leukemic blast samples (P=5.5 * 10(-5)).
      Our genome-wide interrogation of CEU cell lines and primary ALL blasts revealed
      that inherited genomic interindividual variation in a plausible candidate pathway
      can contribute to asparaginase sensitivity.

PMID- 21072046
TI  - A decision analysis of allogeneic hematopoietic stem cell transplantation in
      adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia
      in first remission who have an HLA-matched sibling donor.
AB  - Clinical studies using genetic randomization cannot accurately answer whether
      adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia
      (ALL) who have a human leukocyte antigen (HLA)-matched sibling should undergo
      allogeneic hematopoietic stem cell transplantation (HSCT) or chemotherapy in
      first remission, as, in these studies, patients without a sibling donor undergo
      alternative donor transplantation or chemotherapy alone after a relapse.
      Therefore, we performed a decision analysis to identify the optimal strategy in
      this setting. Transition probabilities and utilities were estimated from
      prospective studies of the Japan Adult Leukemia Study Group, the database of the
      Japan Society for Hematopoietic Cell Transplantation and the literature. The
      primary outcome measure was the 10-year survival probability with or without
      quality of life (QOL) adjustments. Subgroup analyses were performed according to
      risk stratification on the basis of white blood cell count and cytogenetics, and
      according to age stratification. In analyses without QOL adjustments, allogeneic
      HSCT in first remission was superior in the whole population (48.3 vs 32.6%) and
      in all subgroups. With QOL adjustments, a similar tendency was conserved (44.9 vs
      31.7% in the whole population). To improve the probability of long-term survival,
      allogeneic HSCT in first remission is recommended for patients who have an HLA
      matched sibling.

PMID- 21072047
TI  - Multiple forms of PKR present in the nuclei of acute leukemia cells represent an
      active kinase that is responsive to stress.
AB  - A number of cancers possess constitutive activity of the dsRNA-dependent kinase,
      PKR. Inhibition of PKR in these cancers leads to tumor cell death. We recently
      reported the increased presence of PKR phosphorylated on Thr451 (p-T451 PKR) in
      clinical samples from myelodysplastic syndrome (MDS) patients and acute leukemia
      cell lines. Whereas p-T451 PKR in low-risk patient samples or PTEN-positive acute
      leukemia cell lines was mostly cytoplasmic, in high-risk patient samples and
      acute leukemia cell lines deficient in PTEN, p-T451 PKR was mainly nuclear. As
      nuclear activity of PKR has not been previously characterized, we examined the
      status of nuclear PKR in acute leukemia cell lines. Using antibodies to N
      terminus, C-terminus and the kinase domain in conjunction with a proteomics
      approach, we found that PKR exists in diverse molecular weight forms in the
      nucleus. Analysis of PKR transcripts by reverse transcriptase-PCR, and PKR
      derived peptides by MS/MS revealed that these forms were the result of post
      translational modifications (PTMs). Biochemical analysis demonstrated that
      nuclear PKR is an active kinase that can respond to stress. Given the association
      of PKR with PTEN and the Fanconi complex, these results indicate that PKR likely
      has other previously unrecognized roles in nuclear signaling that may contribute
      to leukemic development.

PMID- 21072048
TI  - Expression of S100A8 in leukemic cells predicts poor survival in de novo AML
      patients.
AB  - Cytogenetic stratification remains insufficient for almost half of the acute
      myeloblastic leukemia (AML) cases, with AML patients requiring subsequent
      molecular investigation. In our study, we used mass spectrometry (MS)-based
      proteomic approaches to characterize de novo AML. Fifty-four samples (mononuclear
      cells from bone marrow or peripheral blood mononuclear cells collected and frozen
      before treatment) from two independent cohorts of newly diagnosed AML patients
      were analyzed. We showed that the protein signature of leukemic cells defined two
      clusters that displayed significant variation for overall and disease-free
      survival (P=0.001 and 0.0004, respectively). This proteomic classification
      refines the cytogenetic classes. AML patients with intermediate and unfavorable
      cytogenetic classifications could be subdivided according to their protein
      profiles into subgroups with significantly different survival rates. Among the
      proteins expressed by leukemic cells, we isolated a 10,800-Da marker that
      retained the highest discriminative value between living and deceased patients.
      The 10,800-Da marker was identified by MS peptide sequencing as S100A8 (also
      designated MRP8 or calgranulin A). Western blot analysis confirmed its expression
      mainly in AML patients with the worst prognosis, arguing for a selective
      deregulation associated with poor prognosis. These results suggest that the
      expression of S100A8 in leukemic cells is a predictor of low survival.

PMID- 21072049
TI  - The first case of acute lymphoblastic leukemia with the e19a2 BCR-ABL1
      transcript: imatinib therapy followed by unrelated donor transplantation induces
      a durable molecular response.

PMID- 21072050
TI  - The sequence of application of methotrexate and histone deacetylase inhibitors
      determines either a synergistic or an antagonistic response in childhood acute
      lymphoblastic leukemia cells.

PMID- 21072051
TI  - NADPH oxidases regulate cell growth and migration in myeloid cells transformed by
      oncogenic tyrosine kinases.
AB  - Transformation by tyrosine kinase oncogenes (TKOs) in myeloid malignancies,
      including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia
      or JAK2V617F in myeloproliferative neoplasms, is associated with increased growth
      and cytoskeletal abnormalities. Using targeted approaches against components of
      the superoxide-producing NADPH-oxidases, including NADPH oxidase 2 (NOX2), NOX4
      and the common p22(phox) subunit of NOX1-4, myeloid cells were found to display
      reduced cell growth and spontaneous migration. Consistent with a role of NOXs as
      regulators of membrane proximal signaling events in nonphagocytic cells, NOX2 and
      NOX4 were not involved in the excess production of intracellular reactive oxygen
      species and did not significantly increase oxygen consumption. All NOX family
      members are controlled in part through levels of the rate-limiting substrate
      NADPH, which was found to be significantly elevated in TKO-transformed cells.
      Also, reduced phosphorylation of the actin filament crosslinking protein
      myristoylated alanine-rich C-kinase substrate (MARCKS) in response to suppression
      of p22(phox) hints at a novel effector of NOX signaling. MARCKS was also found to
      be required for increased migration. Overall, these data suggest a model whereby
      NOX links metabolic NADPH production to cellular events that directly contribute
      to transformation.

PMID- 21072052
TI  - Retinoids enhance glucocorticoid-induced apoptosis of T cells by facilitating
      glucocorticoid receptor-mediated transcription.
AB  - Glucocorticoid-induced apoptosis of thymocytes is one of the first recognized
      forms of programmed cell death. It was shown to require gene activation induced
      by the glucocorticoid receptor (GR) translocated into the nucleus following
      ligand binding. In addition, the necessity of the glucocorticoid-induced, but
      transcription-independent phosphorylation of phosphatidylinositol-specific
      phospholipase C (PI-PLC) has also been shown. Here we report that retinoic acids,
      physiological ligands for the nuclear retinoid receptors, enhance glucocorticoid
      induced death of mouse thymocytes both in vitro and in vivo. The effect is
      mediated by retinoic acid receptor (RAR) alpha/retinoid X receptor (RXR)
      heterodimers, and occurs when both RARalpha and RXR are ligated by retinoic
      acids. We show that the ligated RARalpha/RXR interacts with the ligated GR,
      resulting in an enhanced transcriptional activity of the GR. The mechanism
      through which this interaction promotes GR-mediated transcription does not
      require DNA binding of the retinoid receptors and does not alter the
      phosphorylation status of Ser232, known to regulate the transcriptional activity
      of GR. Phosphorylation of PI-PLC was not affected. Besides thymocytes, retinoids
      also promoted glucocorticoid-induced apoptosis of various T-cell lines,
      suggesting that they could be used in the therapy of glucocorticoid-sensitive T
      cell malignancies.

PMID- 21072054
TI  - PTEN status switches cell fate between premature senescence and apoptosis in
      glioma exposed to ionizing radiation.
AB  - Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) has frequently
      been observed in human gliomas, conferring AKT activation and resistance to
      ionizing radiation (IR) and drug treatments. Recent reports have shown that PTEN
      loss or AKT activation induces premature senescence, but many details regarding
      this effect remain obscure. In this study, we tested whether the status of PTEN
      determined fate of the cell by examining PTEN-deficient U87, U251, and U373, and
      PTEN-proficient LN18 and LN428 glioma cells after exposure to IR. These cells
      exhibited different cellular responses, senescence or apoptosis, depending on the
      PTEN status. We further observed that PTEN-deficient U87 cells with high levels
      of both AKT activation and intracellular reactive oxygen species (ROS) underwent
      senescence, whereas PTEN-proficient LN18 cells entered apoptosis. ROS were
      indispensable for inducing senescence in PTEN-deficient cells, but not for
      apoptosis in PTEN-proficient cells. Furthermore, transfection with wild-type (wt)
      PTEN or AKT small interfering RNA induced a change from premature senescence to
      apoptosis and depletion of p53 or p21 prevented IR-induced premature senescence
      in U87 cells. Our data indicate that PTEN acts as a pivotal determinant of cell
      fate, regarding senescence and apoptosis in IR-exposed glioma cells. We conclude
      that premature senescence could have a compensatory role for apoptosis in the
      absence of the tumor suppressor PTEN through the AKT/ROS/p53/p21 signaling
      pathway.

PMID- 21072053
TI  - Illicit survival of cancer cells during polyploidization and depolyploidization.
AB  - Tetraploidy and the depolyploidization of tetraploid cells may contribute to
      oncogenesis. Several mechanisms have evolved to avoid the generation, survival,
      proliferation and depolyploidization of tetraploids. Cells that illicitly survive
      these checkpoints are prone to chromosomal instability and aneuploidization.
      Along with their replication, tetraploids constantly undergo chromosomal
      rearrangements that eventually lead to pseudodiploidy by two non-exclusive
      mechanisms: (i) multipolar divisions and (ii) illicit bipolar divisions in the
      presence of improper microtubule-kinetochore attachments. Here, we describe the
      regulation and the molecular mechanisms that underlie such a 'polyploidization
      depolyploidization' cascade, while focusing on the role of oncogenes and tumor
      suppressor genes in tetraploidy-driven tumorigenesis. We speculate that the
      identification of signaling/metabolic cascades that are required for the survival
      of tetraploid or aneuploid (but not diploid) cancer cells may pave the way for
      the development of novel broad-spectrum anticancer agents.

PMID- 21072055
TI  - IFNgamma triggers a LIGHT-dependent selective death of motoneurons contributing
      to the non-cell-autonomous effects of mutant SOD1.
AB  - Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease
      that primarily affects motoneurons in the brain and spinal cord. Dominant
      mutations in superoxide dismutase-1 (SOD1) cause a familial form of ALS. Mutant
      SOD1-damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic
      factors, but the mechanistic basis of the motoneuron-specific elimination is
      poorly understood. Here, we describe a motoneuron-selective death pathway
      triggered by activation of lymphotoxin-beta receptor (LT-betaR) by LIGHT, and
      operating by a novel signaling scheme. We show that astrocytes expressing mutant
      SOD1 mediate the selective death of motoneurons through the proinflammatory
      cytokine interferon-gamma (IFNgamma), which activates the LIGHT-LT-betaR death
      pathway. The expression of LIGHT and LT-betaR by motoneurons in vivo correlates
      with the preferential expression of IFNgamma by motoneurons and astrocytes at
      disease onset and symptomatic stage in ALS mice. Importantly, the genetic
      ablation of Light in an ALS mouse model retards progression, but not onset, of
      the disease and increases lifespan. We propose that IFNgamma contributes to a
      cross-talk between motoneurons and astrocytes causing the selective loss of some
      motoneurons following activation of the LIGHT-induced death pathway.

PMID- 21072056
TI  - BID is cleaved by caspase-8 within a native complex on the mitochondrial
      membrane.
AB  - Caspase-8 stably inserts into the mitochondrial outer membrane during extrinsic
      apoptosis. Inhibition of caspase-8 enrichment on the mitochondria impairs caspase
      8 activation and prevents apoptosis. However, the function of active caspase-8 on
      the mitochondrial membrane remains unknown. In this study, we have identified a
      native complex containing caspase-8 and BID on the mitochondrial membrane, and
      showed that death receptor activation by Fas or tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) induced the cleavage of BID (tBID formation)
      within this complex. tBID then shifted to separate mitochondria-associated
      complexes that contained other BCL-2 family members, such as BAK and BCL-X(L). We
      report that cells stabilize active caspase-8 on the mitochondria in order to
      specifically target mitochondria-associated BID, and that BID cleavage on the
      mitochondria is essential for caspase-8-induced cytochrome c release. Our
      findings indicate that during extrinsic apoptosis, caspase-8 can specifically
      target BID where it is mostly needed, on the surface of mitochondria.

PMID- 21072057
TI  - Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of
      cytokine-induced Rho signaling.
AB  - Stem cell factor (SCF) and erythropoietin are strictly required for preventing
      apoptosis and stimulating proliferation, allowing the differentiation of
      erythroid precursors from colony-forming unit-E to the polychromatophilic stage.
      In contrast, terminal maturation to generate reticulocytes occurs independently
      of cytokine signaling by a mechanism not fully understood. Terminal
      differentiation is characterized by a sequence of morphological changes including
      a progressive decrease in cell size, chromatin condensation in the nucleus and
      disappearance of organelles, which requires transient caspase activation. These
      events are followed by nucleus extrusion as a consequence of plasma membrane and
      cytoskeleton reorganization. Here, we show that in early step, SCF stimulates the
      Rho/ROCK pathway until the basophilic stage. Thereafter, ROCK-1 is activated
      independently of Rho signaling by caspase-3-mediated cleavage, allowing terminal
      maturation at least in part through phosphorylation of the light chain of myosin
      II. Therefore, in this differentiation system, final maturation occurs
      independently of SCF signaling through caspase-induced ROCK-1 kinase activation.

PMID- 21072058
TI  - Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level.
AB  - TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti
      cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or
      TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells.
      TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies
      still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show
      here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL
      induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with
      TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells.
      This sensitization, which mainly occurs at the death-inducing signaling complex
      (DISC) level, through enhanced caspase-8 recruitment and activation, is
      compromised by c-FLIP expression and is independent of the mitochondria.
      Importantly, TRAIL-R4 expression prevents TRAIL-induced tumor regression in nude
      mice, but tumor regression induced by TRAIL can be restored with chemotherapy.
      Our results clearly support a negative regulatory function for TRAIL-R4 in
      controlling TRAIL signaling, and unveil the ability of TRAIL-R4 to cooperate with
      c-FLIP to inhibit TRAIL-induced cell death.

PMID- 21072059
TI  - Uncovering new substrates for Aurora A kinase.
AB  - Aurora A is a serine/threonine kinase that is essential for a wide variety of
      cell-cycle-related events, but only a small number of its substrates are known.
      We present and validate a strategy by which to identify Aurora A substrates and
      their phosphorylation sites. We developed a computational approach integrating
      various types of biological information to generate a list of 90 potential Aurora
      substrates, with a prediction accuracy of about 80%. We also demonstrated the
      specific phosphorylation of NUSAP (nucleolar and spindle-associated protein) by
      Aurora A in vivo. Our results provide a means by which to develop an
      understanding of Aurora A function and suggest unexpected roles for this kinase.

PMID- 21072060
TI  - The interface between the ubiquitin family and the DNA damage response.
AB  - The crucial role of ubiquitin signalling in genome-integrity maintenance was
      first recognized in 1987 by Stefan Jentsch and Alex Varshavsky, who showed that
      Rad6-the repair protein involved in DNA damage tolerance-is a ubiquitin
      conjugating enzyme. Although this discovery inspired extensive research and led
      to the discovery of genome surveillance pathways that are fuelled by proteolytic
      and regulatory ubiquitylation and SUMOylation, it took more than two decades for
      these fields to meet at a dedicated interdisciplinary conference. This was
      rectified at an EMBO workshop held between 1 and 5 September on Red Island,
      Rovinj, Croatia.

PMID- 21072061
TI  - RNA channelling by the eukaryotic exosome.
AB  - The eukaryotic exosome is a key nuclease for the degradation, processing and
      quality control of a wide variety of RNAs. Here, we report electron microscopic
      reconstructions and pseudo-atomic models of the ten-subunit Saccharomyces
      cerevisiae exosome in the unbound and RNA-bound states. In the RNA-bound
      structures, extra density that is visible at the entry and exit sites of the
      exosome channel indicates that a substrate-threading mechanism is used by the
      eukaryotic exosome. This channelling mechanism seems to be conserved in exosome
      like complexes from all domains of life, and might have been present in the most
      recent common ancestor.

PMID- 21072062
TI  - Poring over exosome structure.

PMID- 21072063
TI  - Receptor for activated C kinase 1 stimulates nascent polypeptide-dependent
      translation arrest.
AB  - Nascent peptide-dependent translation arrest is crucial for the quality control
      of eukaryotic gene expression. Here we show that the receptor for activated C
      kinase 1 (RACK1) participates in nascent peptide-dependent translation arrest,
      and that its binding to the 40S subunit is crucial for this. Translation arrest
      by a nascent peptide results in Dom34/Hbs1-independent endonucleolytic cleavage
      of mRNA, and this is stimulated by RACK1. We propose that RACK1 stimulates the
      translation arrest that is induced by basic amino-acid sequences that leads to
      endonucleolytic cleavage of the mRNA, as well as to co-translational protein
      degradation.

PMID- 21072064
TI  - Fermenting knowledge: the history of winemaking, science and yeast research.

PMID- 21072065
TI  - Giant cell arteritis presenting as macular choroidal ischaemia.

PMID- 21072066
TI  - Scanning beyond the limits of standard OCT with a Fourier domain optical
      coherence tomography integrated into a slit lamp: the SL SCAN-1.
AB  - PURPOSE: With a new Fourier domain optical coherence tomography (FD OCT) device,
      SL SCAN-1 (Topcon Europe Medical BV, Capelle a/d IJssel, The Netherlands),
      integrated into a slit-lamp OCT, scans can be obtained through a handheld lens.
      The necessary adjustment of the reference arm is possible by fast Z-alignment.
      This study was performed to prove the capability of SL SCAN-1 to scan through a
      three-mirror contact lens, scanning the peripheral retina and anterior chamber
      angle. METHODS: Different representative pathologies of the peripheral retina and
      anterior chamber were simultaneously observed and scanned with the SL SCAN-1. The
      scans of peripheral retinal lesions were obtained both through a handheld lens
      and through a three-mirror contact lens. The anterior chamber angle was scanned
      directly with the SL SCAN-1 in anterior mode, and through the gonio-mirror of a
      three-mirror contact lens with the SL SCAN-1 in posterior mode. RESULTS: OCT
      scans could be obtained with the SL SCAN-1 of the peripheral retina through both,
      a common handheld lens and a three-mirror contact lens. The scans obtained
      through a three-mirror contact lens were of better quality, visualizing details
      of the different layers of the retina more clearly. The scans of the anterior
      chamber, obtained through the gonio-mirror of a three-mirror contact lens,
      visualized the open anterior chamber angle, with details of fine structures.
      CONCLUSIONS: The SL SCAN-1 is a unique FD OCT system, which is able to scan not
      only the posterior pole and anterior segment but also the anterior chamber angle
      and the more peripheral retina. These four modalities combined into one device
      could make the SL SCAN-1 a very powerful aid in daily practice.

PMID- 21072067
TI  - BEST1-related autosomal dominant vitreoretinochoroidopathy: a degenerative
      disease with a range of developmental ocular anomalies.
AB  - PURPOSE: To describe the spectrum of phenotypic characteristics of BEST1-related
      autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M
      mutation. METHODS: A retrospective review of the clinical, psychophysical, and
      electrophysiological phenotypes of six subjects with ADVIRC. Five family members
      were sequenced for mutations in the BEST1 gene. RESULTS: A heterozygous change,
      p.V86M (c.256G > A), was identified in the BEST1 gene in the three affected
      subjects tested, and was shown to segregate with the disease phenotype. The
      distance visual acuity ranged from >= 20/25 to absent perception of light.
      Clinical features observed included angle closure glaucoma (n = 2), microcornea
      with shallow anterior chamber (n = 1), iris dysgenesis (n = 2), cataracts (n =
      4), classical peripheral concentric band of retinal hyperpigmentation (n = 5),
      and optic nerve dysplasia (n = 1). Full-field electroretinogram response
      amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable
      (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28
      years) but were abnormal in two older subjects. Optical coherence tomography
      showed macular thinning in the proband, whereas his affected daughter had normal
      macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in
      the lone case tested (27 years). CONCLUSION: ADVIRC is a slowly progressive
      vitreoretinal degeneration that demonstrates marked intra-familial phenotypic
      variability. Optic nerve dysplasia and iris dysgenesis are novel observations
      that extend the ocular phenotype of ADVIRC.

PMID- 21072068
TI  - In vitro and in vivo studies of adenovirus-mediated human norepinephrine
      transporter gene transduction to hepatocellular carcinoma.
AB  - The clinical value of (131)I-MIBG for targeted imaging and targeted radiotherapy
      is limited to neural crest-derived tumors expressing human norepinephrine
      transporters (hNET) protein. To extend (131)I-MIBG-targeted therapy to other
      nonexpressed hNET tumors, this study investigated the hNET expression in vitro
      and in vivo in HepG2 hepatoma mediated by recombinant adenovirus encoding the
      hNET gene (Ad-hNET). For this purpose, the HepG2 cells showed a 4.87-fold
      increase in (125)I-MIBG uptake after infection with Ad-hNET, and the uptake of
      (125)I-MIBG could be specifically inhibited by maprotiline. Immunohistological
      analysis, in vivo biological study and (131)I-MIBG scintigraphic imaging also
      revealed the high expression of hNET protein in hepatoma. This in vitro and in
      vivo studies demonstrate the feasibility of hNET gene transfer, meditated by
      adenovirus vector, could extend to tumors other than those derived from the
      neural crest, which provides a sound foundation for further investigation of
      hepatocellular carcinoma-targeted radiotherapy mediated by adenovirus
      transfection with hNET gene.

PMID- 21072069
TI  - Trigeminal nerve injuries in relation to the local anaesthesia in mandibular
      injections.
AB  - OBJECTIVE: This study reports the signs and symptoms that are the features of
      trigeminal nerve injuries caused by local anaesthesia (LA). METHODS: Thirty-three
      patients with nerve injury following LA were assessed. All data were analysed
      using the SPSS statistical programme and Microsoft Excel. RESULTS: Lingual nerve
      injury (LNI; n = 16) and inferior alveolar nerve injury (IANI; n = 17) patients
      were studied. LNI were more likely to be permanent. Neuropathy was demonstrable
      in all patients with varying degrees of paraesthesia, dysaesthesia (in the form
      of burning pain) allodynia and hyperalgesia. All injuries were unilateral. A
      significantly greater proportion of LNI patients (75%) had received multiple
      injections, in comparison to IANI patients (41%) (p <0.05). Fifty percent of
      patients with LNI reported pain on injection. The presenting signs and symptoms
      of both LNI and IANI included pain. These symptoms of neuropathy were constant in
      88% of the IANI group and in 44% of LNI patients. Functional difficulties were
      different between the LNI and IANI groups, a key difference being the presence of
      severely altered taste perception in nine patients with LA-induced LNI.
      CONCLUSIONS: Chronic pain is often a symptom after local anaesthetic-induced
      nerve injury. Patients in the study population with lingual nerve injury were
      significantly more likely to have received multiple injections compared to those
      with IANI.

PMID- 21072070
TI  - What would you do?

PMID- 21072071
TI  - Politically driven.

PMID- 21072072
TI  - A lot of expensive noise.

PMID- 21072073
TI  - Incorrect and misleading.

PMID- 21072074
TI  - Wake up to endodontics.

PMID- 21072075
TI  - Non-accidental injury.

PMID- 21072076
TI  - Musculoskeletal pain.

PMID- 21072078
TI  - Gaping gob reveal.

PMID- 21072077
TI  - Textbooks wanted.

PMID- 21072079
TI  - Peninsula Dental School celebrates new facility.

PMID- 21072088
TI  - Department of Health is dragging feet on HIV rule.

PMID- 21072093
TI  - Risk management in clinical practice. Part 8. Temporomandibular disorders.
AB  - Temporomandibular disorders can arise apparently idiopathically, as a result of
      macro-trauma or micro-trauma such as parafunction, as a result of a separate
      disease process or as a consequence of dental treatment. The objectives of this
      chapter are to make the practitioner aware of his/her responsibilities in any of
      these situations. Precise record keeping and careful risk management are
      essential. Guidelines are given to protect not only the practitioner but also the
      patient.

PMID- 21072098
TI  - Summary of: Trigeminal nerve injuries in relation to the local anaesthesia in
      mandibular injections.
AB  - OBJECTIVE: This study reports the signs and symptoms that are the features of
      trigeminal nerve injuries caused by local anaesthesia (LA). METHODS: Thirty-three
      patients with nerve injury following LA were assessed. All data were analysed
      using the SPSS statistical programme and Microsoft Excel. RESULTS: Lingual nerve
      injury (LNI; n = 16) and inferior alveolar nerve injury (IANI; n = 17) patients
      were studied. LNI were more likely to be permanent. Neuropathy was demonstrable
      in all patients with varying degrees of paraesthesia, dysaesthesia (in the form
      of burning pain) allodynia and hyperalgesia. All injuries were unilateral. A
      significantly greater proportion of LNI patients (75%) had received multiple
      injections, in comparison to IANI patients (41%) (p <0.05). Fifty percent of
      patients with LNI reported pain on injection. The presenting signs and symptoms
      of both LNI and IANI included pain. These symptoms of neuropathy were constant in
      88% of the IANI group and in 44% of LNI patients. Functional difficulties were
      different between the LNI and IANI groups, a key difference being the presence of
      severely altered taste perception in nine patients with LA-induced LNI.
      CONCLUSIONS: Chronic pain is often a symptom after local anaesthetic-induced
      nerve injury. Patients in the study population with lingual nerve injury were
      significantly more likely to have received multiple injections compared to those
      with IANI.

PMID- 21072099
TI  - Decisions about restorative dental treatment among dentists attending a
      postgraduate continuing professional development course.
AB  - Continuing professional development (CPD) courses seek to inform, educate and
      develop practitioners' patterns of prescribing in line with the evidence base.
      When devising such courses it would be useful for organisers to have some idea of
      what current practice is and the decision-making process as this would inform the
      development of appropriate continuing education courses. A questionnaire
      comprising ten questions was given to 90 dentists at the start of a day's lecture
      course run under Section 63 regulations. The dentists were then shown a series of
      pictures and asked how they would manage each of the cases presented. Eighty-nine
      dentists completed the questionnaire and the results were tabulated and fed back
      to the group at the end of their day's course. Results showed varied and
      inconsistent application of advances in restorative techniques among the
      respondents. Despite a definite interest in more modern treatment options, many
      practitioners continued to support the use of traditional techniques that could
      be considered outdated. Further investigation of the practices of GDPs and their
      decision-making processes would be useful in targeting postgraduate education
      programmes to encourage the uptake of evidence-based practice.

PMID- 21072100
TI  - Gabriel-Philippe de la Hire and the discovery of Hunter-Schreger bands.
AB  - Hunter-Schreger bands are an optical phenomenon observed in mammalian tooth
      enamel. Familiar to all current and former students of dental histology, this
      optical phenomenon appears as alternating patterns of dark and light bands when
      cut enamel is viewed under reflected light. The discovery of this important
      feature of mammalian enamel has been historically credited to two eighteenth
      century investigators, Hunter and Schreger. A re-evaluation of the evidence would
      suggest that the bands were observed almost seventy years earlier by a French
      scientist, Gabriel-Philippe de la Hire, and subsequently confirmed by the famous
      French dentist Pierre Fauchard. This article reviews the contribution of de la
      Hire, as well as that of Fauchard, Hunter and Schreger, to the early recognition
      among the scientific community of what would now be referred to as 'enamel
      microstructure'.

PMID- 21072123
TI  - Characterizing the performance of two optical particle counters (Grimm OPC1.108
      and OPC1.109) under urban aerosol conditions.
AB  - The performance of Grimm optical particle counters (OPC, models 1.108 and 1.109)
      was characterized under urban aerosol conditions. Number concentrations were well
      correlated. The different lower cut-off diameters (0.25 and 0.3 MUm) give an
      average difference of 23.5%. Both detect less than 10% of the total particle
      concentration (0.01-1 MUm; Differential Mobility Analyzer), but in the respective
      size ranges, differences are <10%. OPC number size distributions were converted
      to mass concentrations using instrument-specific factors given by the
      manufacturer. Mass concentrations for OPC1.108 were 60% higher than for OPC1.109
      and (in case of OPC1.109) much lower than those measured with an impactor in the
      relevant size range or a TSP filter. Using the C-factor correction suggested by
      the manufacturer, OPC1.109 underestimated mass concentrations by 21% (impactor)
      and by about 36% (TSP filter), which is in the range of comparability of co
      located different mass concentration methods (Hitzenberger, Berner, Maenhaut,
      Cafmeyer, Schwarz, & Mueller et al., 2004).

PMID- 21072124
TI  - A novel measure to characterise optimality of diameter relationships at retinal
      vascular bifurcations.
AB  - Conventionally, the relationship between parent and daughter vessels at vascular
      bifurcations has been expressed by the junction exponent (x), and deviations of
      this parameter from the optimal conditions predicted by Murray's law (x = 3) have
      been shown to be associated with vascular disease. However, the junction exponent
      is normally calculated iteratively from diameter measurements, and Monte-Carlo
      simulation studies show the junction exponent to be biased in the presence of
      measurement noise.We present an alternative parameter, referred to as optimality
      ratio, that is simpler to compute and also more robust in the presence of
      noise.To demonstrate the sensitivity of the optimality ratio to alterations in
      topography of the retinal vascular network, we analysed the effect of inducing
      endothelial dysfunction by infusion of NG-monomethyl-l-arginine (l-NMMA), a
      nitric oxide synthase inhibitor, compared to placebo in a double-blind crossover
      study. The optimality ratio showed a significant increase (p = 0.03) during
      infusion of l-NMMA compared to placebo.We propose that a measure of the extent of
      departure of optimality ratio from its optimal value of 2(-1/3) may be a useful
      indicator of microvascular endothelial dysfunction in vivo.

PMID- 21072125
TI  - P-C bond formation via P-H addition of a fluoroaryl phosphinic acid to ketones.
AB  - The synthesis, structure and reactivity of the fluoroaryl phosphinic acid
      HF(4)C(6)-P(O)HOH is reported and compared to a sterically comparable yet non
      fluorinated analog with similar size. The fluoroaryl phosphinic acid undergoes
      reversible P-H addition to the carbonyl functionality of ketones under formation
      of a P-C bond which is retained in the resulting alpha-hydroxy phosphinic acid.
      The latter shows an extended 2D hydrogen bonded network in the solid state.

PMID- 21072126
TI  - Applicability of non-destructive substitutes for leaf area in different stands of
      Norway spruce (Picea abies L. Karst.) focusing on traditional forest crown
      measures.
AB  - Since individual tree leaf area is an important measure for productivity as well
      as for site occupancy, it is of high interest in many studies about forest
      growth. The exact determination of leaf area is nearly impossible. Thus, a common
      way to get information about leaf area is to use substitutes. These substitutes
      are often variables which are collected in a destructive way which is not
      feasible for long term studies. Therefore, this study aimed at testing the
      applicability of using substitutes for leaf area which could be collected in a
      non-destructive way, namely crown surface area and crown projection area. In 8
      stands of Norway spruce (Picea abies L. Karst.), divided into three age classes
      and two thinning treatments, a total of 156 trees were felled in order to test
      the relationship between leaf area and crown surface area and crown projection
      area, respectively. Individual tree leaf area of the felled sample trees was
      estimated by 3P-branch sampling with an accuracy of +/-10%. Crown projection area
      and crown surface area were compared with other, more commonly used, but
      destructive predictors of leaf area, namely sapwood area at different heights on
      the bole. Our investigations confirmed findings of several studies that sapwood
      area is the most precise measure for leaf area because of the high correlation
      between sapwood area and the leaf area. But behind sapwood area at crown base and
      sapwood area at three tenth of the tree height the predictive ability of crown
      surface area was ranked third and even better than that of sapwood area at breast
      height (R(2) = 0.656 compared with 0.600). Within the stands leaf area is
      proportional to crown surface area. Using the pooled data of all stands a mixed
      model approach showed that additionally to crown surface area dominant height and
      diameter at breast height (dbh) improved the leaf area estimates. Thus, taking
      dominant height and dbh into account, crown surface area can be recommended for
      estimating the leaf area of individual trees. The resulting model was in line
      with many other findings on the leaf area and leaf mass relationships with crown
      size. From the additional influence of dominant height and dbh in the leaf area
      model we conclude that the used crown model could be improved by estimating the
      position of the maximum crown width and the crown width at the base of the crown
      depending on these two variables.

PMID- 21072127
TI  - WHY INTENSIVE INTERVENTIONS ARE NECESSARY FOR STUDENTS WITH SEVERE READING
      DIFFICULTIES.
AB  - This article reviews research related to intensive interventions within a
      Response to Intervention framework. We review the research from studies that
      provided different levels of intensity of intervention with the goal of
      establishing a case that movement through less intensive tiers of intervention
      may not be an effective and responsible approach to addressing the reading
      difficulties of some students, particularly those with significant reading
      difficulties or disabilities.

PMID- 21072128
TI  - Reading interventions for struggling readers in the upper elementary grades: a
      synthesis of 20 years of research.
AB  - A synthesis of the extant research on reading interventions for students with
      reading difficulties and disabilities in fourth and fifth grade (ages 9-11) is
      presented. Thirteen studies with treatment/comparison study designs and eleven
      single group or single subject studies were located and synthesized. Findings
      from the 24 studies revealed high effects for comprehension interventions on
      researcher-developed comprehension measures. Word recognition interventions
      yielded small to moderate effects on a range of reading outcomes. Few studies
      were located implementing vocabulary and multi-component interventions.

PMID- 21072129
TI  - Anatomical and Physiological Considerations in Vestibular Dysfunction and
      Compensation.
AB  - Sensory information from the vestibular, visual, and somatosensory/proprioceptive
      systems are integrated in the brain in complex ways to produce a final motor
      output to muscle groups for maintaining gaze, head and body posture, and
      controlling static and dynamic balance. The balance system is complex, which can
      make differential diagnosis of dizziness quite challenging. On the other hand,
      this complex system is organized anatomically in a variety of pathways and some
      of these pathways have been well studied. The vestibulo-ocular reflex (VOR) is
      one such pathway. Understanding the anatomy and physiology of the VOR facilitates
      our understanding of normal and abnormal eye movements and research is advancing
      our understanding of the plasticity of the vestibular system. This review
      highlights anatomical and physiological features of the normal vestibular system,
      applies these concepts to explain some clinical findings in some common
      peripheral vestibular disorders, and discusses some of the research investigating
      the anatomical and physiological basis for vestibular compensation.

PMID- 21072131
TI  - The relative effects of group size on reading progress of older students with
      reading difficulties.
AB  - This study reports findings on the relative effects from a yearlong secondary
      intervention contrasting large-group, small-group, and school-provided
      interventions emphasizing word study, vocabulary development, fluency, and
      comprehension with seventh- and eighth-graders with reading difficulties.
      Findings indicate that few statistically significant results or clinically
      significant gains were associated with group size or intervention. Findings also
      indicate that a significant acceleration of reading outcomes for seventh- and
      eighth-graders from high-poverty schools is unlikely to result from a 50 min
      daily class. Instead, the findings indicate, achieving this outcome will require
      more comprehensive models including more extensive intervention (e.g., more time,
      even smaller groups), interventions that are longer in duration (multiple years),
      and interventions that vary in emphasis based on specific students' needs (e.g.,
      increased focus on comprehension or word study).

PMID- 21072130
TI  - Discovering New Reactions with N-Heterocyclic Carbene Catalysis.

PMID- 21072132
TI  - Children's Reasoning about Lie-telling and Truth-telling in Politeness Contexts.
AB  - Children's reasoning about lying and truth-telling was examined among
      participants ages 7-11 (total N = 181) with reference to conflicts between being
      honest and protecting the feelings of others. In Study 1, participants showed
      different patterns of evaluation and motivational inference in politeness
      contexts vs. transgression contexts: in politeness contexts, they rated lie
      telling more favorably and were far more likely to assume that motives were
      prosocial. In Study 2, participants evaluated lie-telling more positively and
      truth-telling more negatively in politeness contexts, especially when they
      focused on the implications of the statements for others instead of whether the
      statements were true or false.

PMID- 21072133
TI  - Chinese Children's Moral Evaluation of Lies and Truths-Roles of Context and
      Parental Individualism-Collectivism Tendencies.
AB  - The present study examined Chinese children's moral evaluations of truths and
      lies about one's own pro-social acts. Children ages 7, 9, and 11 were read
      vignettes in which a protagonist performs a good deed and is asked about it by a
      teacher, either in front of the class or in private. In response, the protagonist
      either tells a modest lie, which is highly valued by the Chinese culture, or
      tells an immodest truth, which violates the Chinese cultural norms about modesty.
      Children were asked to identify whether the protagonist's statement was the truth
      or a lie, and to evaluate how 'good' or 'bad' the statement was. Chinese children
      rated modest lies more positively than immodest truths, with this effect becoming
      more pronounced with age. Rural Chinese children and those with at least one
      nonprofessional parent rated immodest truths less positively when they were told
      in public rather than in private. Furthermore, Chinese children of parents with
      high collectivism scores valued modest lies more than did children of parents
      with low collectivism scores. These findings suggest that both macro- and micro
      cultural factors contribute significantly to children's moral understanding of
      truth and lie telling.

PMID- 21072134
TI  - Considerations for Training Cancer Survivors.
AB  - The incidence of cancer development has reached a plateau while cancer survival
      rates have been increasing. Therefore, more cancer survivors are living with the
      negative effects of cancer and cancer treatments. Exercise can play a significant
      role in combating the negative effects of cancer and cancer treatments and
      improving quality of life during and following clinical treatment for cancer.
      However, exercise interventions must be individualized to optimally meet the
      needs of cancer survivors. This article provides valuable information for
      certified personal trainers regarding the modification of exercise interventions
      to meet the specific needs of the ever increasing population of cancer survivors.

PMID- 21072135
TI  - Novel pharmacological approaches to treatment of drug overdose and addiction.

PMID- 21072136
TI  - Why I Hit Him: Women's Reasons for Intimate Partner Violence.
AB  - This study examines motives for intimate partner violence (IPV) among a community
      sample of 412 women who used IPV against male partners. A "Motives and Reasons
      for IPV scale" is proposed, and exploratory factor analyses identified five
      factors: expression of negative emotions, self-defense, control, jealousy, and
      tough guise. To our knowledge, the study is the first to investigate the
      relationship between women's motives for IPV and their perpetration of physical,
      psychological, and sexual aggression, as well as coercive control, toward
      partners. Hierarchical regression analyses revealed participants' aggression was
      driven by complex, multiple motives. All five motives were related to a greater
      frequency of perpetrating IPV. Treatment programs focusing on women's IPV
      perpetration should address both defensive and proactive motives.

PMID- 21072137
TI  - Quantitation of 6-, 8- and 10-Gingerols and 6-Shogaol in Human Plasma by High
      Performance Liquid Chromatography with Electrochemical Detection.
AB  - Zingiber officinale is one of the most commonly used spices. We developed a
      method to determine the main pungent ginger constituents, 6-, 8- and 10-gingerols
      and 6-shogaol in human plasma. Quantitation was achieved using a reversed-phase
      C(18) column using high-performance liquid chromatography with electrochemical
      detection. The assay was linear from 0.1 to 5.0 MUg/mL. The within-day
      coefficients of variation for the assay at 5.0 MUg/mL were <= 5% for all
      analytes. The recovery of all four analytes was >=99% for at 5.0 MUg/mL. The
      lower limit of quantitation was 0.1 MUg/mL except for 10-gingerol which was 0.25
      MUg/mL. Currently, there is no analytical method for detecting pungent ginger
      constituents in human plasma. This HPLC method allows for the detection of all
      four of ginger's pungent constituents simultaneously in a relatively short run
      time of 25 minutes. This method should be useful for determining plasma levels of
      6-, 8-, 10-gingerol and 6-shogaol in phase I clinical trials.

PMID- 21072138
TI  - Modular Cognitive Therapy for Obsessive-Compulsive Disorder: A Wait-List
      Controlled Trial.
AB  - The current study examined the efficacy of cognitive therapy (CT) in reducing
      symptoms of obsessive-compulsive disorder (OCD). Twenty-nine individuals with OCD
      were assigned according to therapist availability to a 12-week wait period or the
      immediate start of 22 sessions (over 24 weeks) of flexible, modular CT. After 12
      weeks of treatment, the CT group, but not the wait-list group, exhibited
      significant improvement in OCD symptoms. The combined sample of patients who
      underwent 24 weeks of CT improved significantly from pre- to post-treatment and
      symptoms remained significantly improved at 3-month follow-up. OCD symptoms rose
      slightly between posttreatment and 12-month follow-up, but, remained
      significantly lower than at pretreatment. Overall, modular CT appears to be an
      effective and acceptable treatment for OCD.

PMID- 21072139
TI  - A comparative electron correlation treatment in H(2)S-benzene dimer with DFT and
      wavefunction-based ab initio methods.
AB  - Three major conformations of H(2)S-benzene dimer have been located with a variety
      of density functional theories (DFT) and second order Moller-Plesset perturbation
      (MP2). In line with an experiment, MP2 results indicate that the tilted C(s)
      symmetry structure is a stable dimer, yet a C(2v)-symmetry structure is only a
      second-order saddle point. Although all of the examined DFT methods also predict
      the binding between H(2)S and benzene as MP2 and the coupled cluster method with
      single and double excitations and perturbative triples (CCSD(T)) do, they
      considerably underestimate binding energies as compared with CCSD(T) results.
      However, PW91LYP and MPWB1K reproduce the binding sequence obtained with MP2 for
      the dimers, and provide the best binding energies among the tested DFT methods.
      The method of increments with the orbitals of H(2)S and pi orbitals of the
      benzene recovers 99% of the total binding from the full CCSD(T).

PMID- 21072140
TI  - Interferon-gamma Regulates the Death of M. tuberculosis-Infected Macrophages.
AB  - We previously described a caspase-independent death induced in macrophages by a
      high intracellular burden of Mycobacterium tuberculosis (Mtb). This death, with
      features of apoptosis and necrosis, releases viable bacilli for spreading
      infection. Interferon (IFN)-gamma promotes survival of macrophages with a low
      intracellular Mtb load by inhibiting bacterial replication. Macrophages in naive
      hosts are unable to restrict Mtb replication following aerosol transmission, but
      IFN-gamma is increasingly present when adaptive immunity is expressed in the
      lungs ~2 weeks post-infection. We therefore investigated the effects of IFN-gamma
      on macrophages challenged with Mtb at high multiplicity of infection (MOI). In
      contrast to the response at low MOI, IFN-gamma accelerated the death of heavily
      infected macrophages and altered the characteristics of the dying cells. IFN
      gamma increased caspase-dependent DNA cleavage and apoptotic vesicle formation,
      but it also increased mitochondrial injury and release of LDH and HMGB1 in a
      caspase-independent manner. Adaptive immunity in tuberculosis (TB), mediated
      primarily by IFN-gamma, has differential effects on Mtb-induced macrophage cell
      death depending on the intracellular bacillary load. While IFN-gamma generally
      promotes host defense, our data suggest that its effects on heavily infected
      macrophages could also accelerate necrosis and spreading infection in TB disease.

PMID- 21072141
TI  - Generalized Born model with a simple, robust molecular volume correction.
AB  - Generalized Born (GB) models provide a computationally efficient means of
      representing the electrostatic effects of solvent and are widely used, especially
      in molecular dynamics (MD). A class of particularly fast GB models is based on
      integration over an interior volume approximated as a pairwise union of atom
      spheres-effectively, the interior is defined by a van der Waals rather than Lee
      Richards molecular surface. The approximation is computationally efficient, but
      if uncorrected, allows for high dielectric (water) regions smaller than a water
      molecule between atoms, leading to decreased accuracy. Here, an earlier pairwise
      GB model is extended by a simple analytic correction term that largely alleviates
      the problem by correctly describing the solvent-excluded volume of each pair of
      atoms. The correction term introduces a free energy barrier to the separation of
      non-bonded atoms. This free energy barrier is seen in explicit solvent and Lee
      Richards molecular surface implicit solvent calculations, but has been absent
      from earlier pairwise GB models. When used in MD, the correction term yields
      protein hydrogen bond length distributions and polypeptide conformational
      ensembles that are in better agreement with explicit solvent results than earlier
      pairwise models. The robustness and simplicity of the correction preserves the
      efficiency of the pairwise GB models while making them a better approximation to
      reality.

PMID- 21072142
TI  - Cultural Models and Fertility Timing among Cherokee and White Youth in
      Appalachia: Beyond the Mode.

PMID- 21072143
TI  - The Evolution of HIV-1 Diversity in Rural Cameroon and its Implications in
      Vaccine Design and Trials.
AB  - West-Central Africa is an epicenter of the HIV pandemic; endemic to Cameroon are
      HIV-1 viruses belonging to all (sub)subtypes and numerous Circulating Recombinant
      Forms (CRFs). The rural villages of Cameroon harbor many strains of HIV-1, though
      these areas are not as well monitored as the urban centers. In the present study,
      82 specimens obtained in 2000 and 2001 from subjects living in the rural villages
      of the South and West Regions of Cameroon were subtyped in gag, pol, and env and
      compared to 90 specimens obtained in 2006-2008 in the same regions, in order to
      analyze HIV-1 evolution in these rural areas. It was found that in the South
      Region, the proportion of unique recombinant forms (URFs) remained constant
      (~40%), while the amount of URFs containing fragments of a CRF increased by 25%.
      (Sub)subtypes A1, F2, H, and K, and CRF09_cpx, identified in 2000 and 2001, were
      replaced by CRFs 01_AE, 13_cpx, 14_BG, and 18_cpx in 2006-2008. In the West
      Region, (sub)subtypes A2, C, G, and H, and CRFs 01_AE and 09_cpx, identified in
      2000-2001, were replaced by sub-subtype A1 and CRFs 25_cpx and 37_cpx in 2006
      2008. The proportion of URFs in the West Region dropped significantly over the
      time period by 43%. In both Regions, the proportion of CRF02_AG increased at all
      loci. These findings demonstrate that the evolution of HIV-1 is distinct for each
      endemic region, and suggests that the proportion of URFs containing CRF fragments
      is increasing as the genetic identity of the virus continues to shift
      dramatically. This highlights the concern that subtype-specific vaccines may not
      be relevant in Cameroon, and that the distribution of viral diversity in these
      regions of Cameroon must be carefully monitored.

PMID- 21072144
TI  - Genetic demixing and evolution in linear stepping stone models.
AB  - Results for mutation, selection, genetic drift, and migration in a one
      dimensional continuous population are reviewed and extended. The population is
      described by a continuous limit of the stepping stone model, which leads to the
      stochastic Fisher-Kolmogorov-Petrovsky-Piscounov equation with additional terms
      describing mutations. Although the stepping stone model was first proposed for
      population genetics, it is closely related to "voter models" of interest in
      nonequilibrium statistical mechanics. The stepping stone model can also be
      regarded as an approximation to the dynamics of a thin layer of actively growing
      pioneers at the frontier of a colony of micro-organisms undergoing a range
      expansion on a Petri dish. The population tends to segregate into monoallelic
      domains. This segregation slows down genetic drift and selection because these
      two evolutionary forces can only act at the boundaries between the domains; the
      effects of mutation, however, are not significantly affected by the segregation.
      Although fixation in the neutral well-mixed (or "zero-dimensional") model occurs
      exponentially in time, it occurs only algebraically fast in the one-dimensional
      model. An unusual sublinear increase is also found in the variance of the
      spatially averaged allele frequency with time. If selection is weak, selective
      sweeps occur exponentially fast in both well-mixed and one-dimensional
      populations, but the time constants are different. The relatively unexplored
      problem of evolutionary dynamics at the edge of an expanding circular colony is
      studied as well. Also reviewed are how the observed patterns of genetic diversity
      can be used for statistical inference and the differences are highlighted between
      the well-mixed and one-dimensional models. Although the focus is on two alleles
      or variants, q-allele Potts-like models of gene segregation are considered as
      well. Most of the analytical results are checked with simulations and could be
      tested against recent spatial experiments on range expansions of inoculations of
      Escherichia coli and Saccharomyces cerevisiae.

PMID- 21072145
TI  - Neurogenic thoracic outlet syndrome: A case report and review of the literature.
AB  - Neurogenic thoracic outlet syndrome (NTOS) is an oft-overlooked and obscure cause
      of shoulder pain, which regularly presents to the office of shoulder surgeons and
      pain specialist. With this paper we present an otherwise healthy young female
      patient with typical NTOS. She first received repeated conservative treatments
      with 60 units of botulinium toxin injected into the anterior scalene muscle at
      three-month intervals, which providing excellent results of symptom-free periods.
      Later a trans-axillary first rib resection provided semi-permanent relief. The
      patient was followed for 10 years after which time the symptoms reappeared. We
      review the literature and elaborate on the anatomy, sonoanatomy, etiology and
      characteristics, symptoms, diagnostic criteria and treatment modalities of NTOS.
      Patients with NTOS often get operated upon - even if just a diagnostic
      arthroscopy, and an interscalene or other brachial plexus block may be performed.
      This might put the patient in jeopardy of permanent nerve injury, and the purpose
      of this review is to minimize or prevent this.

PMID- 21072146
TI  - Clinical results and motion analysis following arthroscopic anterior
      stabilization of the shoulder using bioknotless anchors.
AB  - PURPOSE: Traumatic anterior dislocation of the shoulder is a common occurrence
      increasingly being treated arthroscopically. This study aims to determine the
      outcome of arthroscopic anterior stabilization using bioknotless anchors and
      analyze the motion in a subset of these patients. MATERIALS AND METHODS: The
      outcome of 20 patients who underwent arthroscopic anterior stabilization using
      the bioknotless system was studied (average follow-up 26 months). Four of these
      patients underwent motion analysis of their shoulder pre- and post-operatively.
      RESULTS: 15% were dissatisfied following surgery and the recurrence of
      instability was also 15%. Those who were dissatisfied or suffered recurrent
      symptoms had statistically significant lower constant scores at the final follow
      up. Pre-operative motion analysis showed a disordered rhythm of shoulder rotation
      which was corrected following surgery with minimal loss of range of motion.
      CONCLUSIONS: Our success rate was comparable to similar arthroscopic techniques
      and results published in the literature. Patient satisfaction depended more on
      return to usual activities than recurrence of symptoms. There was very little
      reduction in range of movement following surgery and the rhythm of shoulder
      motion, particularly external rotation in abduction was improved. LEVEL OF
      EVIDENCE: Four retrospective series.

PMID- 21072147
TI  - The lateral Jobe test: A more reliable method of diagnosing rotator cuff tears.
AB  - PURPOSE: The most reliable clinical investigations to diagnose rotator cuff tears
      reported in the literature is a triad of weakness on resisted external rotation,
      pain on impingement, and weakness on supraspinatus testing, or a combination of
      two of the above in a patient over 60 years of age. We present a simple new
      clinical test "The lateral Jobe Test" and compare it to these combined tests. The
      lateral Jobe test is performed with the patient's shoulder abducted 90 degrees 
      in the coronal plane and internally rotated so that with the elbows flexed 90
      degrees  the fingers point inferiorly and thumbs medially. A positive test is
      pain or weakness on resisting an inferiorly directed force applied to the distal
      arms or an inability to perform the test. MATERIALS AND METHODS: A consecutive
      series of 175 patients undergoing shoulder arthroscopy were reviewed
      prospectively and examined by two independent orthopedic surgeons blinded to the
      diagnosis. The results of the clinical tests were validated against arthroscopic
      findings. RESULTS: The lateral Jobe test had a significantly higher sensitivity
      (81 vs. 58%) than the combined tests. The specificity of both was similar at 89
      and 88%, respectively. CONCLUSION: The lateral Jobe test is a simple single test
      which can help in the clinical diagnosis of rotator cuff tears. LEVEL OF
      EVIDENCE: Level IIb.

PMID- 21072148
TI  - Nonoperative management of a sagittal coracoid fracture with a concomitant
      acromioclavicular joint separation.
AB  - Separation of the acromioclavicular joint in conjunction with a coracoid fracture
      is a rare injury. Treatment decisions are traditionally based on the level of the
      fracture, the status of the coracoclavicular ligament and the activity level of
      the patient. We present a novel coracoid fracture pattern treated nonoperatively
      in a young, active patient and a thorough review of the literature regarding this
      topic.

PMID- 21072149
TI  - Greater auricular nerve neuropraxia with beach chair positioning during shoulder
      surgery.
AB  - Neuropraxia of the greater auricular nerve is an uncommon complication of
      shoulder surgery, with the patient in the beach chair position. The greater
      auricular nerve, a superficial branch of the cervical plexus, is vulnerable to
      neuropraxia due to its superficial anatomical location. In this case series, we
      present three cases of neuropraxia associated with direct compression by a
      horseshoe headrest, used in routine positioning for uncomplicated shoulder
      surgery. We outline the risk of using devices of this nature and discourage the
      use of similar headrest devices due to the potential complications in headrest
      devices that exert pressure on the posterior auricular area to maintain head
      position during surgery.

PMID- 21072150
TI  - Aminoglycoside use in renal failure.
AB  - Aminoglycosides are the mainstay in the treatment of serious gram negative
      infections including catheter-associated infections. They are not metabolized and
      are rapidly excreted as such by glomerular filtration resulting in a plasma
      t(1/2) of approximately two hours in those with normal renal function. The
      t(1/2), however, can extend to 30-60 hours in patients who are functionally
      anephric; therefore, dosage reduction or modification is necessary in renal
      failure patients. In patients on hemodialysis the clearance of aminoglycosides is
      significant and variable. The concept of conventional postdialysis dosing in
      patients on hemodialysis needs to be revised in favor of higher predialysis doses
      to maintain effective bactericidal activity. This article is a brief review of
      the use of aminoglycosides in renal failure patients.

PMID- 21072151
TI  - Iron status, inflammation and hepcidin in ESRD patients: The confounding role of
      intravenous iron therapy.
AB  - Uremia is a state of heightened inflammatory activation. This might have an
      impact on several parameters including anemia management. Inflammation interferes
      with iron utilization in chronic kidney disease through hepcidin. We studied the
      body iron stores, degree of inflammatory activation, and pro-hepcidin levels in
      newly diagnosed patients with end-stage renal disease (ESRD), and compared them
      with normal population. In addition to clinical examination and anthropometry,
      the levels of iron, ferritin, C-reactive protein, tumor necrosis factor alfa,
      interleukin-6, and prohepcidin were estimated. A total of 74 ESRD patients and 52
      healthy controls were studied. The ESRD patients had a significantly lower
      estimated body fat percentage, muscle mass, and albumin; and higher transferrin
      saturation (TSAT) and raised serum ferritin. Inflammatory activation was evident
      in the ESRD group as shown by the significantly higher CRP, IL-6, and TNF-alpha
      levels. The pro-hepcidin levels were also increased in this group. Half of the
      ESRD patients had received parenteral iron before referral. Patients who had
      received intravenous iron showed higher iron, ferritin, and TSAT levels. These
      patients also showed more marked inflammatory activation, as shown by the
      significantly higher CRP, TNF-alpha, and IL-6 levels. We conclude that our ESRD
      patients showed marked inflammatory activation, which was more pronounced in
      patients who had received IV iron. High hepcidin levels could explain the
      functional iron deficiency. The cause of the relatively greater degree of
      inflammatory activation as well as the relationship with IV iron administration
      needs further studies.

PMID- 21072152
TI  - Tuberculin skin test for the diagnosis of latent tuberculosis during renal
      replacement therapy in an endemic area: A single center study.
AB  - Patients on renal replacement therapy (RRT) are at-risk for developing
      tuberculosis (TB). There is limited information on tuberculin skin test (TST) and
      its predictability for development of TB. In this prospective cohort study,
      patients taken for RRT were included. Patients with active TB were excluded. TST
      was done with 5-tuberculin unit. In addition to TST, age, sex, diabetes as basic
      disease, number of dialysis and blood transfusion (BT), pre-transplant TB,
      hepatitis B and C infections and type of immunosuppression were correlated with
      the development of TB. Of the 200 patients included, TST was positive in 21 and
      negative in 179. In TST negative group, 20 (11.1%) and in TST positive group 5
      (23.8%) patients developed TB. TB free survival in two groups was similar (P =
      0.08). On multivariate Cox regression analysis, hazard of development of TB by
      TST was 2.7 [P = 0.11, confidence interval (CI) 0.78-9.7]. There was no
      difference between TST non-responsive and TST negative patients (P = 0.18).
      Sensitivity and specificity of TST for predicting TB was only 20 and 9%,
      respectively. Our study shows that TST in patients on dialysis is an insensitive
      and nonspecific test to predict development of active TB.

PMID- 21072153
TI  - Percutaneous real-time ultrasound-guided renal biopsy performed solely by
      nephrologists: A case series.
AB  - Renal biopsy is an integral part of the nephrologists' diagnostic armamentarium.
      Usually it is performed by radiologists or nephrologists with radiologist's
      assistance. Our aim was to assess the efficacy and safety of percutaneous
      ultrasound-guided renal biopsy performed solely by nephrologists. We performed
      real-time ultrasound-guided renal biopsy on 37 patients (N group). The results
      were then compared with those of a similar number of biopsies done with
      radiologist's support (NR group) immediately prior to these. In the N group, 36
      biopsies (97.3%) were successful and were histopathologically adequate, whereas
      in the NR group, all biopsies were successful but only 28 were adequate (75.68%).
      Eighteen patients required only a single attempt in the N group, whereas majority
      (34 patients) in the NR group required two or more attempts. The average attempt
      per bit of renal tissue was 1.22 in both the groups. The average number of passes
      per patient was 1.77 in the N group and 2.32 in the NR group. The mean size of
      renal tissue obtained was 1.41 +/- 0.47 cm in the N group and 1.19 +/- 0.42 cm in
      the NR group. The average number of glomeruli was 15.62 +/- 5.26 and 13.7 +/-
      7.38 in the N and NR groups, respectively (P<0.05). In the N group, there were no
      complications except two cases of post procedural hematuria that was managed
      conservatively. There was no need for blood transfusion and both of them were
      discharged after 48 hours. No patient had peri-renal collection or hematoma on
      repeat ultrasonography of the abdomen at 24 hours. However, in the NR group, five
      patients developed complications and one patient required laparotomy. Our study
      shows that percutaneous ultrasound-guided renal biopsy can be safely and
      successfully performed entirely by nephrologists without outside assistance. In
      our series, nephrologists who performed solely took fewer attempts, had better
      yield and fewer complications when compared to biopsies performed with
      radiologist's assistance. More and more nephrologists should take up this simple
      yet vital procedure.

PMID- 21072154
TI  - Sildenafil citrate can improve erectile dysfunction among chronic hemodialysis
      patients.
AB  - Erectile dysfunction (ED) is common among patients with end-stage renal disease
      (ESRD), who undergo hemodialysis (HD). The aim of this study was to evaluate the
      safety and effectiveness of sildenafil in male HD patients with ED. Twenty-seven
      HD patients were recruited for this prospective, randomized, double-blind,
      placebo-controlled, clinical trial study of sildenafil during a period of 1 week.
      Efficacy was assessed by using the International Index of Erectile Function
      (IIEF) before and 1 week after treatment. Baseline demographic and clinical
      features were similar in both the groups. There was a weak correlation between ED
      and duration of undergoing dialysis (P = 0.073). There was significant
      relationship between sildenafil usage and improvement in erectile function (P <
      0.0001). Placebo improved significantly the erectile function (P = 0.016),
      perhaps by psychological way. However, sildenafil had a more significant effect
      than placebo in increasing IIEF score among HD patients (P = 0.00 compared to
      0.016). Sildenafil is effective and safe for treating ED among HD patients.

PMID- 21072155
TI  - Effect of gene polymorphisms on the levels of calcineurin inhibitors in Indian
      renal transplant recipients.
AB  - The outcome of renal transplantation is improved by cyclosporine and tacrolimus.
      However, its success is limited by drug-induced nephrotoxicity. Therefore,
      monitoring their levels is important. These levels are influenced mainly by
      CYP3A4, CYP3A5 and MDR- 1 genes. These levels also affect target molecules of
      CNIs, mainly IL-2. Inter-individual differences in these levels have been
      attributed to SNPs in these genes and hence study of these SNPs assumes
      significance. So far no study has been carried out on Indian renal transplant
      recipients covering the SNPs of the genes involved in metabolism, efflux and drug
      target of CNIs, hence the data is lacking for Indian population. The aim is to
      study A-392G SNP of CYP3A4, A6986G SNP of CYP3A5, C3435T SNP of MDR-1 and T-330G
      SNP of IL-2 genes and correlate with CNI blood levels. Hundred healthy subjects
      and 100 consecutive renal transplant recipients; 56 on CsA and 44 on tacrolimus
      were genotyped by PCR followed by restriction enzyme assay for mentioned SNPs. No
      significant difference was observed between level/dose (L/D) ratio of CNIs and
      CYP3A4 and IL-2 SNPs. However, median L/D ratio for tacrolimus was significantly
      higher in subjects with CYP3A5*3/*3 (n = 24) (P = 0.011) and MDR- 1 3435TT (n =
      18) (P = 0.0122). The findings from this study show that homozygous mutant
      patients for CYP3A5 and MDR-1 gene SNPs could be managed with lower tacrolimus
      dose to avoid nephrotoxicity.

PMID- 21072156
TI  - Bilateral renal vein thrombosis and pulmonary embolism secondary to membranous
      glomerulonephritis treated with percutaneous catheter thrombectomy and localized
      thrombolytic therapy.
AB  - Renal vein thrombosis (RVT) is a rare event but is prevalent in patients with
      nephrotic syndrome. Bilateral RVT is even rarer. The literature is relatively
      sparse in terms of the management of RVT because of its rarity and consists of a
      few case reports and case series. We present a case with bilateral RVT
      complicated by a pulmonary embolism in a patient with membranous
      glomerulonephritis (MGN). A 19-year-old female presented with acute flank pain
      and worsening renal function after a couple of weeks in hospital while being
      treated with diuretics for anasarca secondary to MGN. Venography was used for
      diagnosis. The patient underwent percutaneous catheter thrombectomy and localized
      thrombolysis achieving resolution of pain and improvement of renal function. The
      patient was then anticoagulated for life with warfarin.

PMID- 21072157
TI  - Constrictive pericarditis in a renal transplant recipient with tuberculosis.
AB  - Tuberculosis is a common cause of pericarditis in the developing countries and
      constrictive pericarditis is a serious sequel. There are only three cases of
      constrictive pericarditis in kidney transplant recipients previously reported in
      literature. Here, we report a case of constrictive pericarditis developing in a
      renal transplant recipient while on antituberculous therapy for tuberculous
      pleural effusion.

PMID- 21072158
TI  - Cryptococcal sepsis in small vessel vasculitis.
AB  - While meningoencephalitis due to cryptococcus is well known in immunocompromised
      patients, disseminated cryptococcosis and cryptococcemia is rare outside the
      setting of advanced HIV infection. We report a case of disseminated
      cryptococcosis occurring in a patient with Wegener's granulomatosis on
      immunosuppressive medications.

PMID- 21072159
TI  - Child with acute lobar nephronia.
AB  - A five-year-old girl child presented to us with a history of two weeks high grade
      fever treated outside with intensive antibiotic therapy for an ultrasound abdomen
      finding of hypoechoic lesion in the midpole of the left kidney. As fever and
      sonographic findings persisted, a CT abdomen was done, which showed features of
      lobar nephronia but reported as Wilm's tumor. Child underwent open biopsy and the
      diagnosis of lobar nephronia was confirmed. Child was continued on antibiotics
      and fever and sonographic findings improved.

PMID- 21072160
TI  - Delayed diagnosis of pheochromocytoma associated with chronic kidney disease.
AB  - Pheochromocytoma is a rare disease charactrized by excessive production of
      catecholamines, manifestating mainly with hypertension. We report the case of a
      45-year-old woman with history of sudden onset dyspnea, headache, palpitations
      and sudoresis. An abdominal ultrasound was suggestive of chronic kidney disease
      (CKD). An abdominal computed tomography and magnetic resonance was performed and
      showed a mass in the topography of left adrenal. The patient underwent a surgery
      for the removal of the mass and became stable with normal blood pressure levels,
      but remained with CKD. The dalayed diagnosis of pheochromocytoma in the present
      case has contributed to the development of CKD.

PMID- 21072161
TI  - A young lady with abdominal pain and facial lesions.

PMID- 21072162
TI  - Structural studies of the tandem Tudor domains of fragile X mental retardation
      related proteins FXR1 and FXR2.
AB  - BACKGROUND: Expansion of the CGG trinucleotide repeat in the 5'-untranslated
      region of the FMR1, fragile X mental retardation 1, gene results in suppression
      of protein expression for this gene and is the underlying cause of Fragile X
      syndrome. In unaffected individuals, the FMRP protein, together with two
      additional paralogues (Fragile X Mental Retardation Syndrome-related Protein 1
      and 2), associates with mRNA to form a ribonucleoprotein complex in the nucleus
      that is transported to dendrites and spines of neuronal cells. It is thought that
      the fragile X family of proteins contributes to the regulation of protein
      synthesis at sites where mRNAs are locally translated in response to stimuli.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the X-ray crystal structures of
      the non-canonical nuclear localization signals of the FXR1 and FXR2 autosomal
      paralogues of FMRP, which were determined at 2.50 and 1.92 A, respectively. The
      nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain
      architectures, closely resembling that of UHRF1, which is proposed to bind
      methylated histone H3K9. CONCLUSIONS: The FMRP, FXR1 and FXR2 proteins comprise a
      small family of highly conserved proteins that appear to be important in
      translational regulation, particularly in neuronal cells. The crystal structures
      of the N-terminal tandem Tudor domains of FXR1 and FXR2 revealed a conserved
      architecture with that of FMRP. Biochemical analysis of the tandem Tudor domains
      reveals their ability to preferentially recognize trimethylated peptides in a
      sequence-specific manner. ENHANCED VERSION: This article can also be viewed as an
      enhanced version in which the text of the article is integrated with interactive
      3D representations and animated transitions. Please note that a web plugin is
      required to access this enhanced functionality. Instructions for the installation
      and use of the web plugin are available in Text S1.

PMID- 21072163
TI  - Comprehensive approach to analyzing rare genetic variants.
AB  - Recent findings suggest that rare variants play an important role in both
      monogenic and common diseases. Due to their rarity, however, it remains unclear
      how to appropriately analyze the association between such variants and disease. A
      common approach entails combining rare variants together based on a priori
      information and analyzing them as a single group. Here one must make some
      assumptions about what to aggregate. Instead, we propose two approaches to
      empirically determine the most efficient grouping of rare variants. The first
      considers multiple possible groupings using existing information. The second is
      an agnostic "step-up" approach that determines an optimal grouping of rare
      variants analytically and does not rely on prior information. To evaluate these
      approaches, we undertook a simulation study using sequence data from genes in the
      one-carbon folate metabolic pathway. Our results show that using prior
      information to group rare variants is advantageous only when information is quite
      accurate, but the step-up approach works well across a broad range of plausible
      scenarios. This agnostic approach allows one to efficiently analyze the
      association between rare variants and disease while avoiding assumptions required
      by other approaches for grouping such variants.

PMID- 21072164
TI  - The manipulative complexity of Lower Paleolithic stone toolmaking.
AB  - BACKGROUND: Early stone tools provide direct evidence of human cognitive and
      behavioral evolution that is otherwise unavailable. Proper interpretation of
      these data requires a robust interpretive framework linking archaeological
      evidence to specific behavioral and cognitive actions. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we employ a data glove to record manual joint angles in a modern
      experimental toolmaker (the 4(th) author) replicating ancient tool forms in order
      to characterize and compare the manipulative complexity of two major Lower
      Paleolithic technologies (Oldowan and Acheulean). To this end we used a
      principled and general measure of behavioral complexity based on the statistics
      of joint movements. CONCLUSIONS/SIGNIFICANCE: This allowed us to confirm that
      previously observed differences in brain activation associated with Oldowan
      versus Acheulean technologies reflect higher-level behavior organization rather
      than lower-level differences in manipulative complexity. This conclusion is
      consistent with a scenario in which the earliest stages of human technological
      evolution depended on novel perceptual-motor capacities (such as the control of
      joint stiffness) whereas later developments increasingly relied on enhanced
      mechanisms for cognitive control. This further suggests possible links between
      toolmaking and language evolution.

PMID- 21072165
TI  - High-affinity inhibitors of human NAD-dependent 15-hydroxyprostaglandin
      dehydrogenase: mechanisms of inhibition and structure-activity relationships.
AB  - BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the
      key enzyme for the inactivation of prostaglandins, regulating processes such as
      inflammation or proliferation. The anabolic pathways of prostaglandins,
      especially with respect to regulation of the cyclooxygenase (COX) enzymes have
      been studied in detail; however, little is known about downstream events
      including functional interaction of prostaglandin-processing and -metabolizing
      enzymes. High-affinity probes for 15-PGDH will, therefore, represent important
      tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity
      inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS)
      by testing >160 thousand compounds in a concentration-response format and
      identified compounds that act as noncompetitive inhibitors as well as a
      competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused
      strong thermal stabilization of the enzyme, with cofactor dependencies
      correlating with their mechanism of action. We solved the structure of human 15
      PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We
      found binding modes that are consistent with the observed mechanisms of action.
      CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three
      other human dehydrogenases/reductases, suggest selectivity of the present
      inhibitors for 15-PGDH. The high potencies and different mechanisms of action of
      these chemotypes make them a useful set of complementary chemical probes for
      functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This
      article can also be viewed as an enhanced version in which the text of the
      article is integrated with interactive 3D representations and animated
      transitions. Please note that a web plugin is required to access this enhanced
      functionality. Instructions for the installation and use of the web plugin are
      available in Text S2.

PMID- 21072166
TI  - PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new
      functional domain of HIV-1 Vpr proteins.
AB  - BACKGROUND: The hallmark of HIV-1 pathogenesis is the progressive CD4(+) T cell
      depletion and high propensity of CD4(+) T cells to apoptosis. HIV-1 viral protein
      R (Vpr) is a major pro-apoptotic gene product. A first Vpr-mediated apoptotic
      mechanism that requires a physical interaction of HIV-1 Vpr(71-82)
      mitochondriotoxic domain containing the conserved sequence (71-)HFRIGCRHSRIG(-82)
      with the Adenine Nucleotide Translocator (ANT) has been characterized. The family
      of Ser/Thr protein phosphatase PP2A interacts with several viral proteins to
      regulate cell growth and apoptotic pathways. Previous studies based on yeast two
      hybrid assays and mutational experiments indicated that PP2A(1) is involved in
      the induction of G2 arrest by HIV-1 Vpr. PRINCIPAL FINDINGS: Experiments
      combining pull-down, cell penetration and apoptosis analyses in distinct human
      cells indicate that the PP2A(1) binding sequence from Vpr(77-92) is a new cell
      penetrating apoptotic sequence. We also found that the I84P mutation or the
      IIQ/VTR(83-85) and T89A substitutions in the Vpr(77-92) sequence prevent PP2A(1)
      binding, cell penetration and apoptosis. In addition the double R77A and R80A
      mutation known to inactivate the mitochondriotoxic Vpr(71-82) domain, has no
      effect on the biological properties of the Vpr(77-92) domain. CONCLUSION:
      Together our data provide evidence for the first time that the Vpr(77-92)
      sequence delineates a biological active domain of Vpr with PP2A(1) binding and
      pro-apoptotic capacities and, it is conceivable that this cell penetrating
      sequence may account for the Vpr internalization in uninfected cells. Finally,
      our data also implicate the existence of two partially overlapping pro-apoptotic
      domains in the Vpr C-terminal part, a redundancy that represents a new approach
      to address the question of biological relevance of HIV-1 Vpr. In this context,
      future studies will be required to determine the functional relevance of the
      Vpr(77-92) domain in full length Vpr protein and also in entire HIV provirus.

PMID- 21072167
TI  - Dopamine D4 receptor gene associated with fairness preference in ultimatum game.
AB  - In experimental economics, the preference for reciprocal fairness has been
      observed in the controlled and incentivized laboratory setting of the ultimatum
      game, in which two individuals decide on how to divide a sum of money, with one
      proposing the share while the second deciding whether to accept. Should the
      proposal be accepted, the amount is divided accordingly. Otherwise, both would
      receive no money. A recent twin study has shown that fairness preference inferred
      from responder behavior is heritable, yet its neurogenetic basis remains unknown.
      The D4 receptor (DRD4) exon3 is a well-characterized functional polymorphism,
      which is known to be associated with attention deficit hyperactivity disorder and
      personality traits including novelty seeking and self-report altruism. Applying a
      neurogenetic approach, we find that DRD4 is significantly associated with
      fairness preference. Additionally, the interaction among this gene, season of
      birth, and gender is highly significant. This is the first result to link
      preference for reciprocal fairness to a specific gene and suggests that gene *
      environment interactions contribute to economic decision making.

PMID- 21072168
TI  - Transcranial alternating current stimulation enhances individual alpha activity
      in human EEG.
AB  - Non-invasive electrical stimulation of the human cortex by means of transcranial
      direct current stimulation (tDCS) has been instrumental in a number of important
      discoveries in the field of human cortical function and has become a well
      established method for evaluating brain function in healthy human participants.
      Recently, transcranial alternating current stimulation (tACS) has been introduced
      to directly modulate the ongoing rhythmic brain activity by the application of
      oscillatory currents on the human scalp. Until now the efficiency of tACS in
      modulating rhythmic brain activity has been indicated only by inference from
      perceptual and behavioural consequences of electrical stimulation. No direct
      electrophysiological evidence of tACS has been reported. We delivered tACS over
      the occipital cortex of 10 healthy participants to entrain the neuronal
      oscillatory activity in their individual alpha frequency range and compared
      results with those from a separate group of participants receiving sham
      stimulation. The tACS but not the sham stimulation elevated the endogenous alpha
      power in parieto-central electrodes of the electroencephalogram. Additionally, in
      a network of spiking neurons, we simulated how tACS can be affected even after
      the end of stimulation. The results show that spike-timing-dependent plasticity
      (STDP) selectively modulates synapses depending on the resonance frequencies of
      the neural circuits that they belong to. Thus, tACS influences STDP which in turn
      results in aftereffects upon neural activity.The present findings are the first
      direct electrophysiological evidence of an interaction of tACS and ongoing
      oscillatory activity in the human cortex. The data demonstrate the ability of
      tACS to specifically modulate oscillatory brain activity and show its potential
      both at fostering knowledge on the functional significance of brain oscillations
      and for therapeutic application.

PMID- 21072169
TI  - Study of the molecular recognition of aptamers selected through ovarian cancer
      cell-SELEX.
AB  - BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy, and the
      ovarian clear cell carcinoma subtype (OCCA) demonstrates a particularly poor
      response to standard treatment. Improvements in ovarian cancer outcomes,
      especially for OCCA, could be expected from a clearer understanding of the
      molecular pathology that might guide strategies for earlier diagnosis and more
      effective treatment. METHODOLOGY/PRINCIPAL FINDINGS: Cell-SELEX technology was
      employed to develop new molecular probes for ovarian cancer cell surface markers.
      A total of thirteen aptamers with K(d)'s to ovarian cancer cells in the pico- to
      nanomolar range were obtained. Preliminary investigation of the targets of these
      aptamers and their binding characteristics was also performed.
      CONCLUSIONS/SIGNIFICANCE: We have selected a series of aptamers that bind to
      different types of ovarian cancer, but not cervical cancer. Though binding to
      other cancer cell lines was observed, these aptamers could lead to identification
      of biomarkers that are related to cancer.

PMID- 21072170
TI  - PPARgamma downregulation by TGFbeta in fibroblast and impaired expression and
      function in systemic sclerosis: a novel mechanism for progressive fibrogenesis.
AB  - The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma) is expressed in multiple cell types in addition to adipocytes. Upon
      its activation by natural ligands such as fatty acids and eicosanoids, or by
      synthetic agonists such as rosiglitazone, PPAR-gamma regulates adipogenesis,
      glucose uptake and inflammatory responses. Recent studies establish a novel role
      for PPAR-gamma signaling as an endogenous mechanism for regulating transforming
      growth factor-beta (TGF-beta)-dependent fibrogenesis. Here, we sought to
      characterize PPAR-gamma function in the prototypic fibrosing disorder systemic
      sclerosis (SSc), and delineate the factors governing PPAR-gamma expression. We
      report that PPAR-gamma levels were markedly diminished in skin and lung biopsies
      from patients with SSc, and in fibroblasts explanted from the lesional skin. In
      normal fibroblasts, treatment with TGF-beta resulted in a time- and dose
      dependent down-regulation of PPAR-gamma expression. Inhibition occurred at the
      transcriptional level and was mediated via canonical Smad signal transduction.
      Genome-wide expression profiling of SSc skin biopsies revealed a marked
      attenuation of PPAR-gamma levels and transcriptional activity in a subset of
      patients with diffuse cutaneous SSc, which was correlated with the presence of a
      "TGF-beta responsive gene signature" in these biopsies. Together, these results
      demonstrate that the expression and function of PPAR-gamma are impaired in SSc,
      and reveal the existence of a reciprocal inhibitory cross-talk between TGF-beta
      activation and PPAR-gamma signaling in the context of fibrogenesis. In light of
      the potent anti-fibrotic effects attributed to PPAR-gamma, these observations
      lead us to propose that excessive TGF-beta activity in SSc accounts for impaired
      PPAR-gamma function, which in turn contributes to unchecked fibroblast activation
      and progressive fibrosis.

PMID- 21072172
TI  - MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of
      cell cycle.
AB  - MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in
      mice. The MS4A family includes CD20, FcepsilonRIbeta, HTm4 and at least 26 novel
      members that are characterized by their structural features: with four membrane
      spanning domains, two extracellular domains and two cytoplasmic regions. CD20,
      FcepsilonRIbeta and HTm4 have been found to function in B cells, mast cells and
      hematopoietic cells respectively. However, little is known about the function of
      MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates
      mouse T cell proliferation. MS4a4B is highly expressed in primary T cells,
      natural killer cells (NK) and some T cell lines. But its expression in all
      malignant T cells, including thymoma and T hybridoma tested, was silenced.
      Interestingly, its expression was regulated during T cell activation. Viral
      vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells
      reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell
      proliferation. Cell cycle analysis showed that MS4a4B regulated T cell
      proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated
      inhibition of cell cycle was correlated with upregulation of Cdk inhibitory
      proteins and decreased levels of Cdk2 activity, subsequently leading to
      inhibition of cell cycle progression. Our data indicate that MS4a4B negatively
      regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in
      the negative-feedback regulatory loop of activated T cells.

PMID- 21072171
TI  - The regulation of miRNA-211 expression and its role in melanoma cell
      invasiveness.
AB  - The immediate molecular mechanisms behind invasive melanoma are poorly
      understood. Recent studies implicate microRNAs (miRNAs) as important agents in
      melanoma and other cancers. To investigate the role of miRNAs in melanoma, we
      subjected human melanoma cell lines to miRNA expression profiling, and report a
      range of variations in several miRNAs. Specifically, compared with expression
      levels in melanocytes, levels of miR-211 were consistently reduced in all eight
      non-pigmented melanoma cell lines we examined; they were also reduced in 21 out
      of 30 distinct melanoma samples from patients, classified as primary in situ,
      regional metastatic, distant metastatic, and nodal metastatic. The levels of
      several predicted target mRNAs of miR-211 were reduced in melanoma cell lines
      that ectopically expressed miR-211. In vivo target cleavage assays confirmed one
      such target mRNA encoded by KCNMA1. Mutating the miR-211 binding site seed
      sequences at the KCNMA1 3'-UTR abolished target cleavage. KCNMA1 mRNA and protein
      expression levels varied inversely with miR-211 levels. Two different melanoma
      cell lines ectopically expressing miR-211 exhibited significant growth inhibition
      and reduced invasiveness compared with the respective parental melanoma cell
      lines. An shRNA against KCNMA1 mRNA also demonstrated similar effects on melanoma
      cells. miR-211 is encoded within the sixth intron of TRPM1, a candidate
      suppressor of melanoma metastasis. The transcription factor MITF, important for
      melanocyte development and function, is needed for high TRPM1 expression. MITF is
      also needed for miR-211 expression, suggesting that the tumor-suppressor
      activities of MITF and/or TRPM1 may at least partially be due to miR-211's
      negative post transcriptional effects on the KCNMA1 transcript. Given previous
      reports of high KCNMA1 levels in metastasizing melanoma, prostate cancer and
      glioma, our findings that miR-211 is a direct posttranscriptional regulator of
      KCNMA1 expression as well as the dependence of this miRNA's expression on MITF
      activity, establishes miR-211 as an important regulatory agent in human melanoma.

PMID- 21072174
TI  - Laboratory mouse models for the human genome-wide associations.
AB  - The agnostic screening performed by genome-wide association studies (GWAS) has
      uncovered associations for previously unsuspected genes. Knowledge about the
      functional role of these genes is crucial and laboratory mouse models can provide
      such information. Here, we describe a systematic juxtaposition of human GWAS
      discovered loci versus mouse models in order to appreciate the availability of
      mouse models data, to gain biological insights for the role of these genes and to
      explore the extent of concordance between these two lines of evidence. We perused
      publicly available data (NHGRI database for human associations and Mouse Genome
      Informatics database for mouse models) and employed two alternative approaches
      for cross-species comparisons, phenotype- and gene-centric. A total of 293 single
      gene-phenotype human associations (262 unique genes and 69 unique phenotypes)
      were evaluated. In the phenotype-centric approach, we identified all mouse models
      and related ortholog genes for the 51 human phenotypes with a comparable
      phenotype in mice. A total of 27 ortholog genes were found to be associated with
      the same phenotype in humans and mice, a concordance that was significantly
      larger than expected by chance (p<0.001). In the gene-centric approach, we were
      able to locate at least 1 knockout model for 60% of the 262 genes. The knockouts
      for 35% of these orthologs displayed pre- or post-natal lethality. For the
      remaining non-lethal orthologs, the same organ system was involved in mice and
      humans in 71% of the cases (p<0.001). Our project highlights the wealth of
      available information from mouse models for human GWAS, catalogues extensive
      information on plausible physiologic implications for many genes, provides
      hypothesis-generating findings for additional GWAS analyses and documents that
      the concordance between human and mouse genetic association is larger than
      expected by chance and can be informative.

PMID- 21072173
TI  - Evolutionary history of tissue kallikreins.
AB  - The gene family of human kallikrein-related peptidases (KLKs) encodes proteins
      with diverse and pleiotropic functions in normal physiology as well as in disease
      states. Currently, the most widely known KLK is KLK3 or prostate-specific antigen
      (PSA) that has applications in clinical diagnosis and monitoring of prostate
      cancer. The KLK gene family encompasses the largest contiguous cluster of serine
      proteases in humans which is not interrupted by non-KLK genes. This exceptional
      and unique characteristic of KLKs makes them ideal for evolutionary studies
      aiming to infer the direction and timing of gene duplication events. Previous
      studies on the evolution of KLKs were restricted to mammals and the emergence of
      KLKs was suggested about 150 million years ago (mya). In order to elucidate the
      evolutionary history of KLKs, we performed comprehensive phylogenetic analyses of
      KLK homologous proteins in multiple genomes including those that have been
      completed recently. Interestingly, we were able to identify novel reptilian,
      avian and amphibian KLK members which allowed us to trace the emergence of KLKs
      330 mya. We suggest that a series of duplication and mutation events gave rise to
      the KLK gene family. The prominent feature of the KLK family is that it consists
      of tandemly and uninterruptedly arrayed genes in all species under investigation.
      The chromosomal co-localization in a single cluster distinguishes KLKs from
      trypsin and other trypsin-like proteases which are spread in different genetic
      loci. All the defining features of the KLKs were further found to be conserved in
      the novel KLK protein sequences. The study of this unique family will further
      assist in selecting new model organisms for functional studies of proteolytic
      pathways involving KLKs.

PMID- 21072175
TI  - Neonatal mortality and prevalence of practices for newborn care in a squatter
      settlement of Karachi, Pakistan: a cross-sectional study.
AB  - BACKGROUND: During the past two decades there has been a sustained decline in
      child and infant mortality, however neonatal mortality has remained relatively
      unchanged. Almost all neonatal deaths (99%) occur in developing countries, where
      the majority are delivered at homes. Evidence suggests that these deaths could be
      prevented by simple, inexpensive practices and interventions during the
      pregnancy, delivery and postnatal period. In Pakistan over the last decade
      extensive efforts have been made by the international donors and government to
      implement these practices. However, limited attempts have been made to explore if
      these efforts have made a difference at the grass root level. This study assessed
      the burden of neonatal mortality and prevalence of practices for newborn care in
      a squatter settlement of Karachi, Pakistan. METHODOLOGY/PRINCIPAL FINDINGS: A
      community based cross-sectional study was performed. A pre-tested structured
      questionnaire was administered to 565 women who had recently delivered.
      Information was collected on neonatal morbidity, mortality and practices of women
      regarding care during pregnancy, child birth and for newborn, till 28th day of
      birth. Although 70% of women mentioned receiving antenatal care by a skilled
      provider, only 54.5% had four or more visits. Tetanus toxoid was received by 79%
      of women while only 56% delivered at a health care facility by a skilled
      attendant. Newborn care practices like bathing the baby immediately after birth
      (56%), giving pre-lacteals (79.5%), late initiation of breast feeding (80.3%),
      application of substances on umbilical cord (58%) and body massage (89%) were
      common. Most neonates (81.1%) received BCG injection and polio drops after birth.
      Neonatal mortality rate was 27/1000 live births with the majority of deaths
      occurring during the first three days of life. CONCLUSION: Even after years of
      efforts by government and nongovernmental sector to reduce newborn morbidity and
      mortality, inadequate antenatal care, home deliveries and unhealthy newborn care
      practices are highly prevalent. This leads us to important questions of why
      practices and behaviors have not changed. Who is responsible and what strategies
      are needed to bring this change?

PMID- 21072176
TI  - A non-coding RNA within the Rasgrf1 locus in mouse is imprinted and regulated by
      its homologous chromosome in trans.
AB  - BACKGROUND: Rasgrf1 is imprinted in mouse, displaying paternal allele specific
      expression in neonatal brain. Paternal expression is accompanied by paternal
      specific DNA methylation at a differentially methylated domain (DMD) within the
      locus. The cis-acting elements necessary for Rasgrf1 imprinting are known. A
      series of tandem DNA repeats control methylation of the adjacent DMD, which is a
      methylation sensitive enhancer-blocking element. These two sequences constitute a
      binary switch that controls imprinting and represents the Imprinting Control
      Region (ICR). One paternally transmitted mutation, which helped define the ICR,
      induced paramutation, in trans, on the maternal allele. Like many imprinted
      genes, Rasgrf1 lies within an imprinted cluster. One of four noncoding
      transcripts in the cluster, AK015891, is known to be imprinted.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that an additional noncoding
      RNA, AK029869, is imprinted and paternally expressed in brain throughout
      development. Intriguingly, any of several maternally inherited ICR mutations
      affected expression of the paternal AK029869 transcript in trans. Furthermore, we
      found that the ICR mutations exert different trans effects on AK029869 at
      different developmental times. CONCLUSIONS/SIGNIFICANCE: Few trans effects have
      been defined in mammals and, those that exist, do not show the great variation
      seen at the Rasgrf1 imprinted domain, either in terms of the large number of
      mutations that produce the effects or the range of phenotypes that emerge when
      they are seen. These results suggest that trans regulation of gene expression may
      be more common than originally appreciated and that where trans regulation occurs
      it can change dynamically during development.

PMID- 21072177
TI  - IC-tagging and protein relocation to ARV muNS inclusions: a method to study
      protein-protein interactions in the cytoplasm or nucleus of living cells.
AB  - BACKGROUND: Characterization of protein-protein interactions is essential for
      understanding cellular functions. Although there are many published methods to
      analyze protein-protein interactions, most of them present serious limitations.
      In a different study we have characterized a novel avian reovirus muNS-based
      protein tagging and inclusion targeting method, and demonstrated its validity to
      purify free an immobilized protein. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      present a method to identify protein-protein interactions inside living
      eukaryotic cells (tested in primate and avian cells). When p53 was tagged with
      Intercoil (IC; muNS residues 477-542), it not only got integrated into muNS
      cytoplasmic inclusions, but also attracted its known ligand SV40 large T antigen
      (TAg) to these structures. We have also adapted this system to work within the
      cell nucleus, by creating muNS-related protein chimeras that form nuclear
      inclusions. We show that nuclear muNS-derived inclusions are as efficient as
      cytoplasmic ones in capturing IC-tagged proteins, and that the proteins targeted
      to nuclear inclusions are able to interact with their known ligands.
      CONCLUSIONS/SIGNIFICANCE: Our protein redistribution method does not present the
      architectural requirement of re-constructing a transcription factor as any of the
      two-hybrid systems do. The method is simple and requires only cell transfection
      and a fluorescence microscope. Our tagging method can be used either in the
      cytoplasm or the nucleus of living cells to test protein-protein interactions or
      to perform functional studies by protein ligand sequestration.

PMID- 21072178
TI  - The ERCC6 gene and age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of
      irreversible visual loss in the developed countries and is caused by both
      environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an
      association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in
      the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression.
      ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome
      (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks
      of CS. METHODOLOGY/PRINCIPAL FINDINGS: Separate and combined data from three
      large AMD case-control studies and a prospective population-based study (The
      Rotterdam Study) were used to analyse the genetic association between ERCC6 and
      AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in
      retinal pigment epithelium (RPE) cells of healthy and early AMD affected human
      donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the
      Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated
      in two non-European studies (AREDS, Columbia University). In addition, the AMRO
      NL study revealed no significant association for 9 other variants spanning ERCC6.
      Finally, we determined that ERCC6 expression in the human RPE did not depend on
      rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor
      eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018).
      CONCLUSIONS/SIGNIFICANCE: Our meta-analysis of four Caucasian cohorts does not
      replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless,
      our findings on ERCC6 expression in the RPE suggest that ERCC6 may be
      functionally involved in AMD. Combining our data with those of the literature, we
      hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be
      caused by diverse, small and heterogeneous genetic and/or environmental
      determinants.

PMID- 21072179
TI  - Visual laterality of calf-mother interactions in wild whales.
AB  - BACKGROUND: Behavioral laterality is known for a variety of vertebrate and
      invertebrate animals. Laterality in social interactions has been described for a
      wide range of species including humans. Although evidence and theoretical
      predictions indicate that in social species the degree of population level
      laterality is greater than in solitary ones, the origin of these unilateral
      biases is not fully understood. It is especially poorly studied in the wild
      animals. Little is known about the role, which laterality in social interactions
      plays in natural populations. A number of brain characteristics make cetaceans
      most suitable for investigation of lateralization in social contacts.
      METHODOLOGY/PRINCIPAL FINDINGS: Observations were made on wild beluga whales
      (Delphinapterus leucas) in the greatest breeding aggregation in the White Sea.
      Here we show that young calves (in 29 individually identified and in over a
      hundred of individually not recognized mother-calf pairs) swim and rest
      significantly longer on a mother's right side. Further observations along with
      the data from other cetaceans indicate that found laterality is a result of the
      calves' preference to observe their mothers with the left eye, i.e., to analyze
      the information on a socially significant object in the right brain hemisphere.
      CONCLUSIONS/SIGNIFICANCE: Data from our and previous work on cetacean laterality
      suggest that basic brain lateralizations are expressed in the same way in
      cetaceans and other vertebrates. While the information on social partners and
      novel objects is analyzed in the right brain hemisphere, the control of feeding
      behavior is performed by the left brain hemisphere. Continuous unilateral visual
      contacts of calves to mothers with the left eye may influence social development
      of the young by activation of the contralateral (right) brain hemisphere,
      indicating a possible mechanism on how behavioral lateralization may influence
      species life and welfare. This hypothesis is supported by evidence from other
      vertebrates.

PMID- 21072180
TI  - Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI
      resting-state functional connectivity.
AB  - BACKGROUND: Local network connectivity disruptions in Alzheimer's disease
      patients have been found using graph analysis in BOLD fMRI. Other studies using
      MEG and cortical thickness measures, however, show more global long distance
      connectivity changes, both in functional and structural imaging data. The form
      and role of functional connectivity changes thus remains ambiguous. The current
      study shows more conclusive data on connectivity changes in early AD using graph
      analysis on resting-state condition fMRI data. METHODOLOGY/PRINCIPAL FINDINGS: 18
      mild AD patients and 21 healthy age-matched control subjects without memory
      complaints were investigated in resting-state condition with MRI at 1.5 Tesla.
      Functional coupling between brain regions was calculated on the basis of pair
      wise synchronizations between regional time-series. Local (cluster coefficient)
      and global (path length) network measures were quantitatively defined. Compared
      to controls, the characteristic path length of AD functional networks is closer
      to the theoretical values of random networks, while no significant differences
      were found in cluster coefficient. The whole-brain average synchronization does
      not differ between Alzheimer and healthy control groups. Post-hoc analysis of the
      regional synchronization reveals increased AD synchronization involving the
      frontal cortices and generalized decreases located at the parietal and occipital
      regions. This effectively translates in a global reduction of functional long
      distance links between frontal and caudal brain regions.
      CONCLUSIONS/SIGNIFICANCE: We present evidence of AD-induced changes in global
      brain functional connectivity specifically affecting long-distance connectivity.
      This finding is highly relevant for it supports the anterior-posterior
      disconnection theory and its role in AD. Our results can be interpreted as
      reflecting the randomization of the brain functional networks in AD, further
      suggesting a loss of global information integration in disease.

PMID- 21072181
TI  - C/EBPdelta gene targets in human keratinocytes.
AB  - C/EBPs are a family of B-Zip transcription factors--TFs--involved in the
      regulation of differentiation in several tissues. The two most studied members-
      C/EBPalpha and C/EBPbeta--play important roles in skin homeostasis and their
      ablation reveals cells with stem cells signatures. Much less is known about
      C/EBPdelta which is highly expressed in the granular layer of interfollicular
      epidermis and is a direct target of p63, the master regular of multilayered
      epithelia. We identified C/EBPdelta target genes in human primary keratinocytes
      by ChIP on chip and profiling of cells functionally inactivated with siRNA.
      Categorization suggests a role in differentiation and control of cell-cycle,
      particularly of G2/M genes. Among positively controlled targets are numerous
      genes involved in barrier function. Functional inactivation of C/EBPdelta as well
      as overexpressions of two TF targets--MafB and SOX2--affect expression of markers
      of keratinocyte differentiation. We performed IHC on skin tumor tissue arrays:
      expression of C/EBPdelta is lost in Basal Cell Carcinomas, but a majority of
      Squamous Cell Carcinomas showed elevated levels of the protein. Our data indicate
      that C/EBPdelta plays a role in late stages of keratinocyte differentiation.

PMID- 21072182
TI  - Quantification of circulating endothelial progenitor cells using the modified
      ISHAGE protocol.
AB  - AIMS: Circulating endothelial progenitor cells (EPC), involved in endothelial
      regeneration, neovascularisation, and determination of prognosis in
      cardiovascular disease can be characterised with functional assays or using
      immunofluorescence and flow cytometry. Combinations of markers, including
      CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all
      characteristics of EPC. The lack of a standardised protocol with regards to
      reagents and gating strategies may account for the widespread inter-laboratory
      variations in quantification of EPC. We, therefore developed a novel protocol
      adapted from the standardised so-called ISHAGE protocol for enumeration of
      haematopoietic stem cells to enable comparison of clinical and laboratory data.
      METHODS AND RESULTS: In 25 control subjects, 65 patients with coronary artery
      disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial
      infarction (ACS)), EPC were quantified using the following approach: Whole blood
      was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used,
      and finally, CD45(dim)CD34(+) cells were quantified for KDR. A minimum of 100
      CD34(+) events were collected. For comparison, CD45(+)CD34(+) and CD45(-)CD34(+)
      were analysed simultaneously. The number of CD45(dim)CD34(+)KDR(+) cells only
      were significantly higher in healthy controls compared to patients with CAD or
      ACS (p = 0.005 each, p<0.001 for trend). An inverse correlation of
      CD45(dim)CD34(+)KDR(+) with disease activity (r = -0.475, p<0.001) was confirmed.
      Only CD45(dim)CD34(+)KDR(+) correlated inversely with the number of diseased
      coronaries (r = -0.344; p<0.005). In a second study, a 4-week de-novo treatment
      of atorvastatin in stable CAD evoked an increase only of CD45(dim)CD34(+)KDR(+)
      EPC (p<0.05). CD45(+)CD34(+)KDR(+) and CD45(-)CD34(+)KDR(+) were indifferent
      between the three groups. CONCLUSION: Our newly established protocol adopted from
      the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration
      confirming previous findings with respect to the correlation of EPC with disease
      activity and the increase of EPC during statin therapy. The data of this study
      show the CD45(dim) fraction to harbour EPC.

PMID- 21072183
TI  - p21-Activated kinases are required for transformation in a cell-based model of
      neurofibromatosis type 2.
AB  - BACKGROUND: NF2 is an autosomal dominant disease characterized by development of
      bilateral vestibular schwannomas and other benign tumors in central nervous
      system. Loss of the NF2 gene product, Merlin, leads to aberrant Schwann cell
      proliferation, motility, and survival, but the mechanisms by which this tumor
      suppressor functions remain unclear. One well-defined target of Merlin is the
      group I family of p21-activated kinases, which are allosterically inhibited by
      Merlin and which, when activated, stimulate cell cycle progression, motility, and
      increased survival. Here, we examine the effect of Pak inhibition on cells with
      diminished Merlin function. METHODOLOGY/PRINCIPAL FINDINGS: Using a specific
      peptide inhibitor of group I Paks, we show that loss of Pak activity restores
      normal cell movement in cells lacking Merlin function. In addition, xenografts of
      such cells form fewer and smaller tumors than do cells without Pak inhibition.
      However, in tumors, loss of Pak activity does not reduce Erk or Akt activity, two
      signaling proteins that are thought to mediate Pak function in growth factor
      pathways. CONCLUSIONS/SIGNIFICANCE: These results suggest that Pak functions in
      novel signaling pathways in NF2, and may serve as a useful therapeutic target in
      this disease.

PMID- 21072185
TI  - Environmental control of phase transition and polyp survival of a massive
      outbreaker jellyfish.
AB  - A number of causes have been proposed to account for the occurrence of gelatinous
      zooplankton (both jellyfish and ctenophore) blooms. Jellyfish species have a
      complex life history involving a benthic asexual phase (polyp) and a pelagic
      sexual phase (medusa). Strong environmental control of jellyfish life cycles is
      suspected, but not fully understood. This study presents a comprehensive analysis
      on the physicochemical conditions that control the survival and phase transition
      of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the
      Mediterranean Sea. Laboratory experiments indicated that the influence of
      temperature on strobilation and polyp survival was the critical factor
      controlling the capacity of this species to proliferate. Early life stages were
      less sensitive to other factors such as salinity variations or the competitive
      advantage provided by zooxanthellae in a context of coastal eutrophication.
      Coherently with laboratory results, the presence/absence of outbreaks of this
      jellyfish in a particular year seems to be driven by temperature. This is the
      first time the environmental forcing of the mechanism driving the life cycle of a
      jellyfish has been disentangled via laboratory experimentation. Projecting this
      understanding to a field population under climatological variability results in a
      pattern coherent with in situ records.

PMID- 21072186
TI  - The stabilisation potential of individual and mixed assemblages of natural
      bacteria and microalgae.
AB  - It is recognized that microorganisms inhabiting natural sediments significantly
      mediate the erosive response of the bed ("ecosystem engineers") through the
      secretion of naturally adhesive organic material (EPS: extracellular polymeric
      substances). However, little is known about the individual engineering capability
      of the main biofilm components (heterotrophic bacteria and autotrophic
      microalgae) in terms of their individual contribution to the EPS pool and their
      relative functional contribution to substratum stabilisation. This paper
      investigates the engineering effects on a non-cohesive test bed as the surface
      was colonised by natural benthic assemblages (prokaryotic, eukaryotic and mixed
      cultures) of bacteria and microalgae. MagPI (Magnetic Particle Induction) and CSM
      (Cohesive Strength Meter) respectively determined the adhesive capacity and the
      cohesive strength of the culture surface. Stabilisation was significantly higher
      for the bacterial assemblages (up to a factor of 2) than for axenic microalgal
      assemblages. The EPS concentration and the EPS composition (carbohydrates and
      proteins) were both important in determining stabilisation. The peak of
      engineering effect was significantly greater in the mixed assemblage as compared
      to the bacterial (x 1.2) and axenic diatom (x 1.7) cultures. The possibility of
      synergistic effects between the bacterial and algal cultures in terms of
      stability was examined and rejected although the concentration of EPS did show a
      synergistic elevation in mixed culture. The rapid development and overall
      stabilisation potential of the various assemblages was impressive (x 7.5 and
      *9.5, for MagPI and CSM, respectively, as compared to controls). We confirmed the
      important role of heterotrophic bacteria in "biostabilisation" and highlighted
      the interactions between autotrophic and heterotrophic biofilm consortia. This
      information contributes to the conceptual understanding of the microbial sediment
      engineering that represents an important ecosystem function and service in
      aquatic habitats.

PMID- 21072184
TI  - Flavopiridol pharmacogenetics: clinical and functional evidence for the role of
      SLCO1B1/OATP1B1 in flavopiridol disposition.
AB  - BACKGROUND: Flavopiridol is a cyclin-dependent kinase inhibitor in phase II
      clinical development for treatment of various forms of cancer. When administered
      with a pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited
      striking activity in patients with refractory chronic lymphocytic leukemia. This
      study aimed to evaluate pharmacogenetic factors associated with inter-individual
      variability in pharmacokinetics and outcomes associated with flavopiridol
      therapy. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five patients who received single
      agent flavopiridol via the PK-directed schedule were genotyped for 189
      polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters.
      Genotypes were evaluated in univariate and multivariate analyses as covariates in
      a population PK model. Transport of flavopiridol and its glucuronide metabolite
      was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently
      transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and
      SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate
      analysis. Transport assay results indicated both flavopiridol and flavopiridol
      glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates
      incorporated into the final population PK model included bilirubin, SLCO1B1
      rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype
      and response. To validate these findings, a second set of data with 51 patients
      was evaluated, and overall trends for associations between PK and PGx were found
      to be consistent. CONCLUSIONS/SIGNIFICANCE: Polymorphisms in transport genes were
      found to be associated with flavopiridol disposition and outcomes. Observed
      clinical associations with SLCO1B1 were functionally validated indicating for the
      first time its relevance as a transporter of flavopiridol and its glucuronide
      metabolite. A second 51-patient dataset indicated similar trends between genotype
      in the SLCO1B1 and other candidate genes, thus providing support for these
      findings. Further study in larger patient populations will be necessary to fully
      characterize and validate the clinical impact of polymorphisms in SLCO1B1 and
      other transporter and metabolizing enzyme genes on outcomes from flavopiridol
      therapy.

PMID- 21072187
TI  - Evidence for significant overlap between common risk variants for Crohn's disease
      and ankylosing spondylitis.
AB  - BACKGROUND: A multicenter genome-wide association scan for Crohn's Disease (CD)
      has recently reported 40 CD susceptibility loci, including 29 novel ones (19
      significant and 10 putative). To gain insight into the genetic overlap between CD
      and ankylosing spondylitis (AS), these markers were tested for association in AS
      patients. PRINCIPAL FINDINGS: Two previously established associations, namely
      with the MHC and IL23R loci, were confirmed. In addition, rs2872507, which maps
      to a locus associated with asthma and influences the expression of the ORMDL3
      gene in lymphoblastoid cells, showed a significant association with AS (p =
      0.03). In gut biopsies of AS and CD patients, ORMDL3 expression was not
      significantly different from controls and no correlation was found with the
      rs2872507 genotype (Spearman's rho: -0.067). The distribution of p-values for the
      remaining 36 SNPs was significantly skewed towards low p-values unless the top 5
      ranked SNPs (ORMDL3, NKX2-3, PTPN2, ICOSLG and MST1) were excluded from the
      analysis. CONCLUSIONS: Association analysis using risk variants for CD led to the
      identification of a new risk variant associated with AS (ORMDL3), underscoring a
      role for ER stress in AS. In addition, two known and five potentially relevant
      associations were detected, contributing to common susceptibility of CD and AS.

PMID- 21072188
TI  - The impact of case diagnosis coverage and diagnosis delays on the effectiveness
      of antiviral strategies in mitigating pandemic influenza A/H1N1 2009.
AB  - BACKGROUND: Neuraminidase inhibitors were used to reduce the transmission of
      pandemic influenza A/H1N1 2009 at the early stages of the 2009/2010 pandemic.
      Policies for diagnosis of influenza for the purposes of antiviral intervention
      differed markedly between and within countries, leading to differences in the
      timing and scale of antiviral usage. METHODOLOGY/PRINCIPAL FINDINGS: The impact
      of the percentage of symptomatic infected individuals who were diagnosed, and of
      delays to diagnosis, for three antiviral intervention strategies (each with and
      without school closure) were determined using a simulation model of an Australian
      community. Epidemic characteristics were based on actual data from the A/H1N1
      2009 pandemic including reproduction number, serial interval and age-specific
      infection rate profile. In the absence of intervention an illness attack rate
      (AR) of 24.5% was determined from an estimated R(0) of 1.5; this was reduced to
      21%, 16.5% or 13% by treatment-only, treatment plus household prophylaxis, or
      treatment plus household plus extended prophylaxis antiviral interventions
      respectively, assuming that diagnosis occurred 24 hours after symptoms arose and
      that 50% of symptomatic cases were diagnosed. If diagnosis occurred without
      delay, ARs decreased to 17%, 12.2% or 8.8% respectively. If 90% of symptomatic
      cases were diagnosed (with a 24 hour delay), ARs decreased to 17.8%, 11.1% and
      7.6%, respectively. CONCLUSION: The ability to rapidly diagnose symptomatic cases
      and to diagnose a high proportion of cases was shown to improve the effectiveness
      of all three antiviral strategies. For epidemics with R(0)< = 1.5 our results
      suggest that when the case diagnosis coverage exceeds ~70% the size of the
      antiviral stockpile required to implement the extended prophylactic strategy
      decreases. The addition of at least four weeks of school closure was found to
      further reduce cumulative and peak attack rates and the size of the required
      antiviral stockpile.

PMID- 21072189
TI  - RNA polymerase II binding patterns reveal genomic regions involved in microRNA
      gene regulation.
AB  - MicroRNAs are small non-coding RNAs involved in post-transcriptional regulation
      of gene expression. Due to the poor annotation of primary microRNA (pri-microRNA)
      transcripts, the precise location of promoter regions driving expression of many
      microRNA genes is enigmatic. This deficiency hinders our understanding of
      microRNA-mediated regulatory networks. In this study, we develop a computational
      approach to identify the promoter region and transcription start site (TSS) of
      pri-microRNAs actively transcribed using genome-wide RNA Polymerase II (RPol II)
      binding patterns derived from ChIP-seq data. Based upon the assumption that the
      distribution of RPol II binding patterns around the TSS of microRNA and protein
      coding genes are similar, we designed a statistical model to mimic RPol II
      binding patterns around the TSS of highly expressed, well-annotated promoter
      regions of protein coding genes. We used this model to systematically scan the
      regions upstream of all intergenic microRNAs for RPol II binding patterns similar
      to those of TSS from protein coding genes. We validated our findings by examining
      the conservation, CpG content, and activating histone marks in the identified
      promoter regions. We applied our model to assess changes in microRNA
      transcription in steroid hormone-treated breast cancer cells. The results
      demonstrate many microRNA genes have lost hormone-dependent regulation in
      tamoxifen-resistant breast cancer cells. MicroRNA promoter identification based
      upon RPol II binding patterns provides important temporal and spatial
      measurements regarding the initiation of transcription, and therefore allows
      comparison of transcription activities between different conditions, such as
      normal and disease states.

PMID- 21072190
TI  - Proteome analysis of Borrelia burgdorferi response to environmental change.
AB  - We examined global changes in protein expression in the B31 strain of Borrelia
      burgdorferi, in response to two environmental cues (pH and temperature) chosen
      for their reported similarity to those encountered at different stages of the
      organism's life cycle. Multidimensional nano-liquid chromatographic separations
      coupled with tandem mass spectrometry were used to examine the array of proteins
      (i.e., the proteome) of B. burgdorferi for different pH and temperature culture
      conditions. Changes in pH and temperature elicited in vitro adaptations of this
      spirochete known to cause Lyme disease and led to alterations in protein
      expression that are associated with increased microbial pathogenesis. We
      identified 1,031 proteins that represent 59% of the annotated genome of B.
      burgdorferi and elucidated a core proteome of 414 proteins that were present in
      all environmental conditions investigated. Observed changes in protein abundances
      indicated varied replicon usage, as well as proteome functional distributions
      between the in vitro cell culture conditions. Surprisingly, the pH and
      temperature conditions that mimicked B. burgdorferi residing in the gut of a fed
      tick showed a marked reduction in protein diversity. Additionally, the results
      provide us with leading candidates for exploring how B. burgdorferi adapts to and
      is able to survive in a wide variety of environmental conditions and lay a
      foundation for planned in situ studies of B. burgdorferi isolated from the tick
      midgut and infected animals.

PMID- 21072191
TI  - Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa.
AB  - BACKGROUND: Antiretroviral therapy (ART) has been scaled-up rapidly in Africa.
      Programme reports typically focus on loss to follow-up and mortality among
      patients receiving ART. However, little is known about linkage and retention in
      care of individuals prior to starting ART. METHODOLOGY: Data on adult residents
      from a periurban community in Cape Town were collected at a primary care clinic
      and hospital. HIV testing registers, CD4 count results provided by the National
      Health Laboratory System and ART registers were linked. A random sample (n = 885)
      was drawn from adults testing HIV positive through antenatal care, sexual
      transmitted disease and voluntary testing and counseling services between January
      2004 and March 2009. All adults (n = 103) testing HIV positive through TB
      services during the same time period were also included in the study. Linkage to
      HIV care was defined as attending for a CD4 count measurement within 6 months of
      HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months
      of HIV diagnosis in individuals with a CD4 count <=200 cells/ul taken within 6
      months of HIV diagnosis. FINDINGS: Only 62.6% of individuals attended for a CD4
      count measurement within 6 months of testing HIV positive. Individuals testing
      through sexually transmitted infection services had the best (84.1%) and
      individuals testing on their own initiative (53.5%) the worst linkage to HIV
      care. One third of individuals with timely CD4 counts were eligible for ART and
      66.7% of those were successfully linked to ART care. Linkage to ART care was
      highest among antenatal care clients. Among individuals not yet eligible for ART
      only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients
      tested in more recent calendar period. CONCLUSION: Linkage to HIV and ART care
      was low in this poor peri-urban community despite free services available within
      close proximity. More efforts are needed to link VCT scale-up to subsequent care.

PMID- 21072192
TI  - Factors affecting the introduction of new vaccines to poor nations: a comparative
      study of the Haemophilus influenzae type B and hepatitis B vaccines.
AB  - BACKGROUND: A major effort to introduce new vaccines into poor nations of the
      world was initiated in recent years with the help of the GAVI alliance. The first
      vaccines introduced have been the Haemophilus influenzae type B (Hib) and the
      hepatitis B (Hep B) vaccines. The introduction of these vaccines during the first
      phase of GAVI's operations demonstrated considerable variability. We set out to
      study the factors affecting the introduction of these vaccines. The African
      Region (AFRO), where new vaccines were introduced to a substantial number of
      countries during the first phase of GAVI's funding, was selected for this study.
      METHODOLOGY/PRINCIPAL FINDINGS: GAVI-eligible AFRO countries with a population of
      0.5 million or more were included in the study. Countries were analyzed and
      compared for new vaccine introduction, healthcare indicators, financial
      indicators related to healthcare and country-level Governance Indicators, using
      One Way ANOVA, correlation analysis and Qualitative Comparative Analysis (QCA).
      Introduction of new vaccines into AFRO nations was associated primarily with high
      country-level Governance Indicator scores. The use of individual Governance
      Indicator scores, as well as a combined Governance Indicator score we developed,
      demonstrated similar results. CONCLUSIONS/SIGNIFICANCE: Our study results
      indicate that good country-level governance is an imperative pre-requisite for
      the successful early introduction of new vaccines into poor African nations.
      Enhanced support measures may be required to effectively introduce new vaccines
      to countries with low governance scores. The combined governance score we
      developed may thus constitute a useful tool for helping philanthropic
      organizations make decisions regarding the type of support needed by different
      countries to achieve success.

PMID- 21072193
TI  - Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift
      valley fever virus in human small airway epithelial cells.
AB  - Rift valley fever virus (RVFV) infection is an emerging zoonotic disease endemic
      in many countries of sub-Saharan Africa and in Egypt. In this study we show that
      human small airway epithelial cells are highly susceptible to RVFV virulent
      strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein
      arrays technology to identify phosphoprotein signaling pathways modulated during
      infection of cultured airway epithelium. ZH-501 infection induced activation of
      MAP kinases (p38, JNK and ERK) and downstream transcriptional factors [STAT1
      (Y701), ATF2 (T69/71), MSK1 (S360) and CREB (S133)]. NF-kappaB phosphorylation
      was also increased. Activation of p53 (S15, S46) correlated with the increased
      levels of cleaved effector caspase-3, -6 and -7, indicating activation of the
      extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a
      major anti-apoptotic regulator of survival pathways, AKT (S473), along with
      phosphorylation of FOX 01/03 (T24/31) which controls cell cycle arrest downstream
      from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was
      decreased. However, the intrinsic apoptotic pathway marker, caspase-9,
      demonstrated only a marginal activation accompanied by an increased level of the
      inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker,
      LC3B, which often accompanies the pro-survival signaling, was decreased.
      Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral
      strategy directed toward the control of cell apoptosis through a number of
      transcriptional factors. Analyses of MP-12 titers in challenged cells in the
      presence of MAPK inhibitors indicated that activation of p38 represents a
      protective cell response while ERK activation controls viral replication.

PMID- 21072194
TI  - Dynamic distribution of histone H4 arginine 3 methylation marks in the developing
      murine cortex.
AB  - BACKGROUND: Epigenetic modifications regulate key transitions in cell fate during
      development of the central nervous system (CNS). During cortical development the
      initial population of proliferative neuroepithelial precursor cells give rise to
      neurons and then glia in a strict temporal order. Neurogenesis and gliogenesis
      are accompanied by a switch from symmetric to asymmetric divisions of the neural
      precursor cells generating another precursor and a differentiated progeny. To
      investigate whether specific post-translational histone modifications define
      specific stages of neural precursor differentiation during cortical development I
      focussed on the appearance of two different types of histone arginine
      methylation, the dimethyl symmetric H4R3 (H4R3me2s) and dimethyl asymmetric H4R3
      (H4R3me2a) in the developing mouse cortex. METHODOLOGY/PRINCIPAL FINDINGS: An
      immunohistochemical study of the developing cortex at different developmental
      stages was performed to detect the distribution of H4R3me2s and H4R3me2a
      modifications. I analysed the distribution of these modifications in: 1)
      undifferentiated neural precursors, 2) post-mitotic neurons and 3) developing
      oligodendrocyte precursors (OLPs) using lineage-specific and histone modification
      specific antibodies to co-label the cells. I found that the proliferative
      neuroepithelium during the stage of mainly symmetric expansive divisions is
      characterised by the prevalence of H4R3me2s modification and almost no detectable
      H4R3me2a modification. However, at a later stage, when the cortical layers with
      post-mitotic neurons have begun forming, both H4R3me2a and H4R3me2s modifications
      are detected in the post-mitotic neurons and in the developing OLPs.
      CONCLUSIONS/SIGNIFICANCE: I propose that the H4R3me2s modification forms part of
      the "histone code" of undifferentiated neural precursors. The later appearance of
      the H4R3me2a modifications specifies the onset of neurogenesis and gliogenesis
      and the commitment of the NSCs to differentiate. Thus, the sequential appearance
      of the two different H4R3 methylation marks may define a particular cellular
      state of the NSCs during their development and differentiation demonstrating the
      role of histone arginine methylation in cortical development.

PMID- 21072195
TI  - Characteristic metabolism of free amino acids in cetacean plasma: cluster
      analysis and comparison with mice.
AB  - From an evolutionary perspective, the ancestors of cetaceans first lived in
      terrestrial environments prior to adapting to aquatic environments. Whereas
      anatomical and morphological adaptations to aquatic environments have been well
      studied, few studies have focused on physiological changes. We focused on plasma
      amino acid concentrations (aminograms) since they show distinct patterns under
      various physiological conditions. Plasma and urine aminograms were obtained from
      bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer
      whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to
      uncover a multitude of amino acid relationships among different species, which
      can help us understand the complex interrelations comprising metabolic
      adaptations. The cetacean aminograms formed a cluster that was markedly
      distinguishable from the mouse cluster, indicating that cetaceans and terrestrial
      mammals have quite different metabolic machinery for amino acids. Levels of
      carnosine and 3-methylhistidine, both of which are antioxidants, were
      substantially higher in cetaceans. Urea was markedly elevated in cetaceans,
      whereas the level of urea cycle-related amino acids was lower. Because diving
      mammals must cope with high rates of reactive oxygen species generation due to
      alterations in apnea/reoxygenation and ischemia-reperfusion processes, high
      concentrations of antioxidative amino acids are advantageous. Moreover, shifting
      the set point of urea cycle may be an adaptation used for body water conservation
      in the hyperosmotic sea water environment, because urea functions as a major
      blood osmolyte. Furthermore, since dolphins are kept in many aquariums for
      observation, the evaluation of these aminograms may provide useful diagnostic
      indices for the assessment of cetacean health in artificial environments in the
      future.

PMID- 21072196
TI  - Profiling gene expression induced by protease-activated receptor 2 (PAR2)
      activation in human kidney cells.
AB  - Protease-Activated Receptor-2 (PAR2) has been implicated through genetic knockout
      mice with cytokine regulation and arthritis development. Many studies have
      associated PAR2 with inflammatory conditions (arthritis, airways inflammation,
      IBD) and key events in tumor progression (angiogenesis, metastasis), but they
      have relied heavily on the use of single agonists to identify physiological roles
      for PAR2. However such probes are now known not to be highly selective for PAR2,
      and thus precisely what PAR2 does and what mechanisms of downstream regulation
      are truly affected remain obscure. Effects of PAR2 activation on gene expression
      in Human Embryonic Kidney cells (HEK293), a commonly studied cell line in PAR2
      research, were investigated here by comparing 19,000 human genes for intersecting
      up- or down-regulation by both trypsin (an endogenous protease that activates
      PAR2) and a PAR2 activating hexapeptide (2f-LIGRLO-NH(2)). Among 2,500 human
      genes regulated similarly by both agonists, there were clear associations between
      PAR2 activation and cellular metabolism (1,000 genes), the cell cycle, the MAPK
      pathway, HDAC and sirtuin enzymes, inflammatory cytokines, and anti-complement
      function. PAR-2 activation up-regulated four genes more than 5 fold (DUSP6, WWOX,
      AREG, SERPINB2) and down-regulated another six genes more than 3 fold (TXNIP,
      RARG, ITGB4, CTSD, MSC and TM4SF15). Both PAR2 and PAR1 activation resulted in up
      regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB,
      CORO1C, THBS1, SDC4) known to be important in cancer. This is the first
      widespread profiling of specific activation of PAR2 and provides a valuable
      platform for better understanding key mechanistic roles of PAR2 in human
      physiology. Results clearly support the development of both antagonists and
      agonists of human PAR2 as potential disease modifying therapeutic agents.

PMID- 21072197
TI  - Population genetic differences along a latitudinal cline between original and
      recently colonized habitat in a butterfly.
AB  - BACKGROUND: Past and current range or spatial expansions have important
      consequences on population genetic structure. Habitat-use expansion, i.e.
      changing habitat associations, may also influence genetic population parameters,
      but has been less studied. Here we examined the genetic population structure of a
      Palaeartic woodland butterfly Pararge aegeria (Nymphalidae) which has recently
      colonized agricultural landscapes in NW-Europe. Butterflies from woodland and
      agricultural landscapes differ in several phenotypic traits (including
      morphology, behavior and life history). We investigated whether phenotypic
      divergence is accompanied by genetic divergence between populations of different
      landscapes along a 700 km latitudinal gradient. METHODOLOGY/PRINCIPAL FINDINGS:
      Populations (23) along the latitudinal gradient in both landscape types were
      analyzed using microsatellite and allozyme markers. A general decrease in genetic
      diversity with latitude was detected, likely due to post-glacial colonization
      effects. Contrary to expectations, agricultural landscapes were not less diverse
      and no significant bottlenecks were detected. Nonetheless, a genetic signature of
      recent colonization is reflected in the absence of clinal genetic differentiation
      within the agricultural landscape, significantly lower gene flow between
      agricultural populations (3.494) than between woodland populations (4.183), and
      significantly higher genetic differentiation between agricultural (0.050) than
      woodland (0.034) pairwise comparisons, likely due to multiple founder events.
      Globally, the genetic data suggest multiple long distance dispersal/colonization
      events and subsequent high intra- and inter-landscape gene flow in this species.
      Phosphoglucomutase deviated from other enzymes and microsatellite markers, and
      hence may be under selection along the latitudinal gradient but not between
      landscape types. Phenotypic divergence was greater than genetic divergence,
      indicating directional selection on some flight morphology traits. MAIN
      CONCLUSIONS/SIGNIFICANCE: Clinal differentiation characterizes the population
      structure within the original woodland habitat. Genetic signatures of recent
      habitat expansion remain, notwithstanding high gene flow. After differentiation
      through drift was excluded, both latitude and landscape were significant factors
      inducing spatially variable phenotypic variation.

PMID- 21072198
TI  - Global health: a successful context for precollege training and advocacy.
AB  - Despite a flourishing biomedical and global health industry too few of Washington
      state's precollege students are aware of this growing sector and emerging ideas
      on bacteria, fungi, parasites and viruses. Against the backdrop of numerous
      reports regarding declining precollege student interest in science, a precollege
      program was envisioned at Seattle Biomedical Research Institute (as of 2010,
      Seattle BioMed) to increase youth engagement in biomedical research and global
      health, increase community interest in infectious diseases and mobilize a future
      biomedical workforce. Since 2005, 169 rising high school juniors have
      participated in the BioQuest Academy precollege immersion program at Seattle
      BioMed. Assembling in groups of 12, students conduct laboratory experiments
      (e.g., anopheline mosquito dissection, gene expression informed tuberculosis drug
      design and optimizing HIV immunization strategies) related to global health
      alongside practicing scientific mentors, all within the footprint the institute.
      Laudable short-term impacts of the program include positive influences on student
      interest in global health (as seen in the students' subsequent school projects
      and their participation in Seattle BioMed community events), biomedical careers
      and graduate school (e.g., 16.9% of teens departing 2008-2009 Academy report
      revised goals of attaining a doctorate rather than a baccalaureate diploma). Long
      term, 97% of alumni (2005-2008) are attending postsecondary schools throughout
      North America; eight graduates have already published scientific articles in peer
      reviewed journals and/or presented their scientific data at national and
      international meetings, and 26 have been retained by Seattle BioMed researchers
      as compensated technicians and interns. Providing precollege students with
      structured access to practicing scientists and authentic research environments
      within the context of advancing global health has been a robust means of both
      building a future pool of talented leaders and engaged citizenry and increasing
      the visibility of health disparities within the community.

PMID- 21072199
TI  - Effects of hydrographic variability on the spatial, seasonal and diel diving
      patterns of southern elephant seals in the eastern Weddell Sea.
AB  - Weddell Sea hydrography and circulation is driven by influx of Circumpolar Deep
      Water (CDW) from the Antarctic Circumpolar Current (ACC) at its eastern margin.
      Entrainment and upwelling of this high-nutrient, oxygen-depleted water mass
      within the Weddell Gyre also supports the mesopelagic ecosystem within the gyre
      and the rich benthic community along the Antarctic shelf. We used Conductivity
      Temperature-Depth Satellite Relay Data Loggers (CTD-SRDLs) to examine the
      importance of hydrographic variability, ice cover and season on the movements and
      diving behavior of southern elephant seals in the eastern Weddell Sea region
      during their overwinter feeding trips from Bouvetoya. We developed a model
      describing diving depth as a function of local time of day to account for diel
      variation in diving behavior. Seals feeding in pelagic ice-free waters during the
      summer months displayed clear diel variation, with daytime dives reaching 500
      1500 m and night-time targeting of the subsurface temperature and salinity maxima
      characteristic of CDW around 150-300 meters. This pattern was especially clear in
      the Weddell Cold and Warm Regimes within the gyre, occurred in the ACC, but was
      absent at the Dronning Maud Land shelf region where seals fed benthically. Diel
      variation was almost absent in pelagic feeding areas covered by winter sea ice,
      where seals targeted deep layers around 500-700 meters. Thus, elephant seals
      appear to switch between feeding strategies when moving between oceanic regimes
      or in response to seasonal environmental conditions. While they are on the shelf,
      they exploit the locally-rich benthic ecosystem, while diel patterns in pelagic
      waters in summer are probably a response to strong vertical migration patterns
      within the copepod-based pelagic food web. Behavioral flexibility that permits
      such switching between different feeding strategies may have important
      consequences regarding the potential for southern elephant seals to adapt to
      variability or systematic changes in their environment resulting from climate
      change.

PMID- 21072200
TI  - Ionotropic glutamate receptor AMPA 1 is associated with ovulation rate.
AB  - Ionotropic glutamate receptors mediate most excitatory neurotransmission in the
      central nervous system by opening ion channels upon the binding of glutamate.
      Despite the essential roles of glutamate in the control of reproduction and
      anterior pituitary hormone secretion, there is a limited understanding of how
      glutamate receptors control ovulation. Here we reveal the function of the
      ionotropic glutamate receptor AMPA-1 (GRIA1) in ovulation. Based on a genome-wide
      association study in Bos taurus, we found that ovulation rate is influenced by a
      variation in the N-terminal leucine/isoleucine/valine-binding protein (LIVBP)
      domain of GRIA1, in which serine is replaced by asparagine. GRIA1(Asn) has a
      weaker affinity to glutamate than GRIA1(Ser), both in Xenopus oocytes and in the
      membrane fraction of bovine brain. This single amino acid substitution leads to
      the decreased release of gonadotropin-releasing hormone (GnRH) in immortalized
      hypothalamic GT1-7 cells. Cows with GRIA1(Asn) have a slower luteinizing hormone
      (LH) surge than cows with GRIA1(Ser). In addition, cows with GRIA1(Asn) possess
      fewer immature ovarian follicles before superovulation and have a lower response
      to hormone treatment than cows with GRIA1(Ser). Our work identified that GRIA1 is
      a critical mediator of ovulation and that GRIA1 might be a useful target for
      reproductive therapy.

PMID- 21072201
TI  - Genome-wide and follow-up studies identify CEP68 gene variants associated with
      risk of aspirin-intolerant asthma.
AB  - Aspirin-intolerant asthma (AIA) is a rare condition that is characterized by the
      development of bronchoconstriction in asthmatic patients after ingestion of non
      steroidal anti-inflammatory drugs including aspirin. However, the underlying
      mechanisms of AIA occurrence are still not fully understood. To identify the
      genetic variations associated with aspirin intolerance in asthmatics, the first
      stage of genome-wide association study with 109,365 single nucleotide
      polymorphisms (SNPs) was undertaken in a Korean AIA (n = 80) cohort and aspirin
      tolerant asthma (ATA, n = 100) subjects as controls. For the second stage of
      follow-up study, 150 common SNPs from 11 candidate genes were genotyped in 163
      AIA patients including intermediate AIA (AIA-I) subjects and 429 ATA controls.
      Among 11 candidate genes, multivariate logistic analyses showed that SNPs of
      CEP68 gene showed the most significant association with aspirin intolerance (P
      values of co-dominant for CEP68, 6.0*10(-5) to 4.0*10(-5)). All seven SNPs of the
      CEP68 gene showed linkage disequilibrium (LD), and the haplotype of CEP68_ht4 (T
      G-A-A-A-C-G) showed a highly significant association with aspirin intolerance
      (OR= 2.63; 95% CI= 1.64-4.21; P = 6.0*10(-5)). Moreover, the nonsynonymous CEP68
      rs7572857G>A variant that replaces glycine with serine showed a higher decline of
      forced expiratory volume in 1s (FEV(1)) by aspirin provocation than other
      variants (P = 3.0*10(-5)). Our findings imply that CEP68 could be a susceptible
      gene for aspirin intolerance in asthmatics, suggesting that the nonsynonymous
      Gly74Ser could affect the polarity of the protein structure.

PMID- 21072202
TI  - Comparison of HIV prevalence estimates for Zimbabwe from antenatal clinic
      surveillance (2006) and the 2005-06 Zimbabwe Demographic and Health Survey.
AB  - OBJECTIVE: To assess whether HIV surveillance data from pregnant women attending
      antenatal care (ANC) clinics in Zimbabwe represent infection levels in the
      general population. METHODS: HIV prevalence estimates from ANC surveillance sites
      in 2006 were compared with estimates from the corresponding Zimbabwe Demographic
      and Health Survey 2005-06 (ZDHS) clusters using geographic information systems.
      RESULTS: The ANC HIV prevalence estimate (17.9%, 95% CI 17.0%-18.8%) was similar
      to the ZDHS estimates for all men and women aged 15-49 years (18.1%, 16.9%
      18.8%), for pregnant women (17.5%, 13.9%-21.9%), and for ANC attendees living
      within 30 km of ANC surveillance sites (19.9%, 17.1%-22.8%). However, the ANC
      surveillance estimate (17.9%) was lower than the ZDHS estimates for all women
      (21.1%, 19.7%-22.6%) and for women living within 30 km catchment areas of ANC
      surveillance sites (20.9%, 19.4%-22.3%). HIV prevalence in ANC sites classified
      as urban and rural was significantly lower than in sites classified as "other".
      CONCLUSIONS: Periodic population surveys can be used to validate ANC surveillance
      estimates. In Zimbabwe, ANC surveillance provides reliable estimates of HIV
      prevalence among men and women aged 15-49 years in the general population. Three
      classifications of ANC sites (rural/urban/other) should be used when generating
      national HIV estimates.

PMID- 21072203
TI  - Lactic acid induces aberrant amyloid precursor protein processing by promoting
      its interaction with endoplasmic reticulum chaperone proteins.
AB  - BACKGROUND: Lactic acid, a natural by-product of glycolysis, is produced at
      excess levels in response to impaired mitochondrial function, high-energy demand,
      and low oxygen availability. The enzyme involved in the production of beta
      amyloid peptide (Abeta) of Alzheimer's disease, BACE1, functions optimally at
      lower pH, which led us to investigate a potential role of lactic acid in the
      processing of amyloid precursor protein (APP). METHODOLOGY/PRINCIPAL FINDINGS:
      Lactic acid increased levels of Abeta40 and 42, as measured by ELISA, in culture
      medium of human neuroblastoma cells (SH-SY5Y), whereas it decreased APP
      metabolites, such as sAPPalpha. In cell lysates, APP levels were increased and
      APP was found to interact with ER-chaperones in a perinuclear region, as
      determined by co-immunoprecipitation and fluorescence microscopy studies. Lactic
      acid had only a very modest effect on cellular pH, did increase the levels of ER
      chaperones Grp78 and Grp94 and led to APP aggregate formation reminiscent of
      aggresomes. CONCLUSIONS/SIGNIFICANCE: These findings suggest that sustained
      elevations in lactic acid levels could be a risk factor in amyloidogenesis
      related to Alzheimer's disease through enhanced APP interaction with ER chaperone
      proteins and aberrant APP processing leading to increased generation of amyloid
      peptides and APP aggregates.

PMID- 21072204
TI  - FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their
      potential as biomarkers for surveillance and therapy.
AB  - BACKGROUND: Fifty percent of patients with muscle-invasive bladder cancer (MI-BC)
      die from their disease and current chemotherapy treatment only marginally
      increases survival. Novel therapies targeting receptor tyrosine kinases or
      activated oncogenes may improve outcome. Hence, it is necessary to stratify
      patients based on mutations in relevant oncogenes. Patients with non-muscle
      invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds
      develop recurrences. Tumor specific mutations can be used to detect recurrences
      in urine assays, presenting a more patient-friendly diagnostic procedure than
      cystoscopy. METHODOLOGY/PRINCIPAL FINDINGS: To address these issues, we developed
      a mutation assay for the simultaneous detection of 19 possible mutations in the
      HRAS, KRAS, and NRAS genes. With this assay and mutation assays for the FGFR3 and
      PIK3CA oncogenes, we screened primary bladder tumors of 257 patients and 184
      recurrences from 54 patients. Additionally, in primary tumors p53 expression was
      obtained by immunohistochemistry. Of primary tumors 64% were mutant for FGFR3,
      11% for RAS, 24% for PIK3CA, and 26% for p53. FGFR3 mutations were mutually
      exclusive with RAS mutations (p = 0.001) and co-occurred with PIK3CA mutations (p
      = 0.016). P53 overexpression was mutually exclusive with PIK3CA and FGFR3
      mutations (p<=0.029). Mutations in the RAS and PIK3CA genes were not predictors
      for recurrence-free, progression-free and disease-specific survival. In patients
      presenting with NMI-BC grade 3 and MI-BC, 33 and 36% of the primary tumors were
      mutant. In patients with low-grade NMI-BC, 88% of the primary tumors carried a
      mutation and 88% of the recurrences were mutant. CONCLUSIONS/SIGNIFICANCE: The
      mutation assays present a companion diagnostic to define patients for targeted
      therapies. In addition, the assays are a potential biomarker to detect
      recurrences during surveillance. We showed that 88% of patients presenting with
      low-grade NMI-BC are eligible for such a follow-up. This may contribute to a
      reduction in the number of cystoscopical examinations.

PMID- 21072205
TI  - Regulation and cytoprotective role of hexokinase III.
AB  - BACKGROUND: Hexokinases (HKs) catalyze the first step in glucose metabolism. Of
      the three mammalian 100-kDa HK isoforms, HKI and II can bind to mitochondria and
      protect against cell death. HKIII does not bind mitochondria, and little is known
      about its regulation or cytoprotective effects. We studied the regulation of
      HKIII at the transcriptional and protein levels and investigated its role in
      cellular protection. METHODOLOGY/PRINCIPAL FINDINGS: We show that like HKII,
      HKIII expression is regulated by hypoxia, but other factors that regulate HKII
      expression have no effect on HKIII levels. This transcriptional regulation is
      partially dependent on hypoxia-inducible factor (HIF) signaling. We also
      demonstrate regulation at the protein level, as mutations in putative N-terminal
      substrate binding residues altered C-terminal catalytic activity, suggesting that
      HKIII activity is governed, in part, by interactions between these two domains.
      Overexpression of HKIII reduced oxidant-induced cell death, increased ATP levels,
      decreased the production of reactive oxygen species (ROS), and preserved
      mitochondrial membrane potential. HKIII overexpression was also associated with
      higher levels of transcription factors that regulate mitochondrial biogenesis,
      and greater total mitochondrial DNA content. Attempts to target HKIII to the
      mitochondria by replacing its N-terminal 32-amino-acid sequence with the
      mitochondrial-targeting sequence of HKII led to protein aggregation, suggesting
      that this region is necessary to maintain proper protein folding and solubility.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that HKIII is regulated by
      hypoxia and there are functional interactions between its two halves.
      Furthermore, HKIII exerts protective effects against oxidative stress, perhaps by
      increasing ATP levels, reducing oxidant-induced ROS production, preserving
      mitochondrial membrane potential, and increasing mitochondrial biogenesis.

PMID- 21072206
TI  - Hearing loss in stranded odontocete dolphins and whales.
AB  - The causes of dolphin and whale stranding can often be difficult to determine.
      Because toothed whales rely on echolocation for orientation and feeding, hearing
      deficits could lead to stranding. We report on the results of auditory evoked
      potential measurements from eight species of odontocete cetaceans that were found
      stranded or severely entangled in fishing gear during the period 2004 through
      2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed
      dolphins had significant hearing deficits with a reduction in sensitivity
      equivalent to severe (70-90 dB) or profound (>90 dB) hearing loss in humans. The
      only stranded short-finned pilot whale examined had profound hearing loss. No
      impairments were detected in seven Risso's dolphins from three different
      stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one
      spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could
      play a significant role in some cetacean stranding events, and the hearing of all
      cetaceans in rehabilitation should be tested.

PMID- 21072207
TI  - Maternal environmental contribution to adult sensitivity and resistance to
      obesity in Long Evans rats.
AB  - BACKGROUND: The OLETF rat is an animal model of early onset hyperphagia induced
      obesity, presenting multiple pre-obese characteristics during the suckling
      period. In the present study, we used a cross-fostering strategy to assess
      whether interactions with obese dams in the postnatal environment contributed to
      the development of obesity. METHODOLOGY: On postnatal Day (PND)-1 OLETF and
      control LETO pups were cross-fostered to same or opposite strain dams. An
      independent ingestion test was performed on PND11 and a nursing test on PND18.
      Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin,
      cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat
      pads were collected and weighed and adipocyte size and number were estimated.
      Body weight and intake, as well as the estrous cycle of the female offspring were
      monitored. PRINCIPAL FINDINGS: During the suckling period, the pups' phenotype
      was almost completely determined by the strain of the mother. However, pups
      independently ingested food according to their genotype, regardless of their
      actual phenotype. At adulthood, cross fostered males of both strains and LETO
      females were affected in regard of their adiposity levels in the direction of the
      foster dam. On the other hand, OLETF females showed almost no alterations in
      adiposity but were affected by the strain of the dams in parameters related to
      the metabolic syndrome. Thus, OLETF females showed reduced liver adiposity and
      circulating levels of ALT, while LETO females presented a disrupted estrous cycle
      and increased cholesterol and triglycerides in the long term. CONCLUSIONS: The
      present study provides further support for the early postnatal environment
      playing a sex-divergent role in programming later life phenotype. In addition, it
      plays a more central role in determining the functioning of mechanisms involved
      in energy balance that may provide protection from or sensitivity to later life
      obesity and pathologies related to the metabolic syndrome.

PMID- 21072208
TI  - Contribution of plasminogen activation towards the pathogenic potential of oral
      streptococci.
AB  - Oral streptococci are a heterogeneous group of human commensals, with a potential
      to cause serious infections. Activation of plasminogen has been shown to increase
      the virulence of typical human pathogenic streptococci such as S. pneumoniae. One
      important factor for plasminogen activation is the streptococcal alpha-enolase.
      Here we report that plasminogen activation is also common in oral streptococci
      species involved in clinical infection and that it depends on the action of human
      plasminogen activators. The ability to activate plasminogen did not require full
      conservation of the internal plasminogen binding sequence motif FYDKERKVY of
      alpha-enolase that was previously described as crucial for increased plasminogen
      binding, activation and virulence. Instead, experiments with recombinant alpha
      enolase variants indicate that the naturally occurring variations do not impair
      plasminogen binding. In spite of these variations in the internal plasminogen
      binding motif oral streptococci showed similar activation of plasminogen. We
      conclude that the pathomechanism of plasminogen activation is conserved in oral
      streptococci that cause infections in human. This may contribute to their
      opportunistic pathogenic character that is unfurled in certain niches.

PMID- 21072209
TI  - Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects.
AB  - BACKGROUND: Escherichia coli AlkB is a 2-oxoglutarate- and iron-dependent
      dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse
      AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of
      mammalian dioxygenases. METHODS AND FINDINGS: In the present study we show non
      Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1(-/-) and
      heterozygous Alkbh1(+/-) offspring are born at a greatly reduced frequency.
      Additionally, the sex-ratio is considerably skewed against female offspring, with
      one female born for every three to four males. Most mechanisms that cause
      segregation distortion, act in the male gametes and affect male fertility. The
      skewing of the sexes appears to be of paternal origin, and might be set in the
      pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is
      upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5
      10% of the tubules in Alkbh1(-/-) adults. The deficiency of Alkbh1 also causes
      misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is
      consistent with the incompletely penetrant phenotypes observed, particularly
      recurrent unilateral eye defects and craniofacial malformations. CONCLUSIONS:
      Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation
      in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio
      distribution and embryonic development in mice.

PMID- 21072210
TI  - Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon
      receptor agonist.
AB  - BACKGROUND: Cancer stem cells (CSCs) have increased resistance to cancer
      chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with
      chemotherapeutic drugs, and/or by sorting of cells expressing CSC markers such as
      aldehyde dehydrogenase-1 (ALDH). CSCs form colonies in agar, mammospheres in low
      adherence cultures, and tumors following xenotransplantation in Scid mice. We
      hypothesized that tranilast, a non-toxic orally active drug with anti-cancer
      activities, would inhibit breast CSCs. METHODOLOGY/FINDINGS: We examined breast
      cancer cell lines or D-CSCs generated by growth of these cells with mitoxantrone.
      Tranilast inhibited colony formation, mammosphere formation and stem cell marker
      expression. Mitoxantrone-selected cells were enriched for CSCs expressing stem
      cell markers ALDH, c-kit, Oct-4, and ABCG2, and efficient at forming
      mammospheres. Tranilast markedly inhibited mammosphere formation by D-CSCs and
      dissociated formed mammospheres, at pharmacologically relevant concentrations. It
      was effective against D-CSCs of both HER-2+ and triple-negative cell lines.
      Tranilast was also effective in vivo, since it prevented lung metastasis in mice
      injected i.v. with triple-negative (MDA-MB-231) mitoxantrone-selected cells. The
      molecular targets of tranilast in cancer have been unknown, but here we
      demonstrate it is an aryl hydrocarbon receptor (AHR) agonist and this plays a key
      role. AHR is a transcription factor activated by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD), polycyclic aromatic hydrocarbons and other ligands. Tranilast
      induced translocation of the AHR to the nucleus and stimulated CYP1A1 expression
      (a marker of AHR activation). It inhibited binding of the AHR to CDK4, which has
      been linked to cell-cycle arrest. D-CSCs expressed higher levels of the AHR than
      other cells. Knockdown of the AHR with siRNA, or blockade with an AHR antagonist,
      entirely abrogated the anti-proliferative and anti-mammosphere activity of
      tranilast. Thus, the anti-cancer effects of tranilast are AHR dependent.
      CONCLUSION/SIGNIFICANCE: We show that tranilast is an AHR agonist with inhibitory
      effects on breast CSCs. It is effective against CSCs of triple-negative breast
      cancer cells selected for anti-cancer drug resistance. These results suggest it
      might find applications in the treatment of breast cancer.

PMID- 21072211
TI  - Hepatocyte growth factor modulates interleukin-6 production in bone marrow
      derived macrophages: implications for inflammatory mediated diseases.
AB  - The generation of the pro-inflammatory cytokines IL-6, TNF-alpha, and IL-1beta
      fuel the acute phase response (APR). To maintain body homeostasis, the increase
      of inflammatory proteins is resolved by acute phase proteins via presently
      unknown mechanisms. Hepatocyte growth factor (HGF) is transcribed in response to
      IL-6. Since IL-6 production promotes the generation of HGF and induces the APR,
      we posited that accumulating HGF might be a likely candidate for quelling excess
      inflammation under non-pathological conditions. We sought to assess the role of
      HGF and how it influences the regulation of inflammation utilizing a well-defined
      model of inflammatory activation, lipopolysaccharide (LPS)-stimulation of bone
      marrow derived macrophages (BMM). BMM were isolated from C57BL6 mice and were
      stimulated with LPS in the presence or absence of HGF. When HGF was present,
      there was a decrease in production of the pro-inflammatory cytokine IL-6, along
      with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine
      production correlated with an increase in phosphorylated GSK3beta, increased
      retention of the phosphorylated NFkappaB p65 subunit in the cytoplasm, and an
      enhanced interaction between CBP and phospho-CREB. These changes were a direct
      result of signaling through the HGF receptor, MET, as effects were reversed in
      the presence of a selective inhibitor of MET (SU11274) or when using BMM from
      macrophage-specific conditional MET knockout mice. Combined, these data provide
      compelling evidence that under normal circumstances, HGF acts to suppress the
      inflammatory response.

PMID- 21072212
TI  - The association of AMPK with ULK1 regulates autophagy.
AB  - Autophagy is a highly orchestrated intracellular bulk degradation process that is
      activated by various environmental stresses. The serine/threonine kinase ULK1,
      like its yeast homologue Atg1, is a key initiator of autophagy that is negatively
      regulated by the mTOR kinase. However, the molecular mechanism that controls the
      inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood.
      Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner.
      We found that AMPK binds to the PS domain of ULK1 and this interaction is
      required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR
      induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with
      raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces
      autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant
      raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken
      together, these results suggest that AMPK association with ULK1 plays an
      important role in autophagy induction, at least in part, by phosphorylation of
      raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex.

PMID- 21072213
TI  - CD4+CD25+Foxp3+ regulatory T cells depletion may attenuate the development of
      silica-induced lung fibrosis in mice.
AB  - BACKGROUND: Silicosis is an occupational lung disease caused by inhalation of
      silica dust characterized by lung inflammation and fibrosis. Previous study
      showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2
      polarization during the development of silicosis is still a matter of debate.
      Regulatory T cells (Treg cells) represent a crucial role in modulation of immune
      homeostasis by regulating Th1/Th2 polarization, but their possible implication in
      silicosis remains to be explored. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the
      implication of Treg cells in the development of silicosis, we generated the Treg
      depleted mice model by administration of anti-CD25 mAbs and mice were exposed to
      silica by intratracheal instillation to establish experimental model of silica
      induced lung fibrosis. The pathologic examinations show that the Treg-depleted
      mice are susceptive to severer inflammation in the early stage, with enhanced
      infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay
      of the progress of silica-induced lung fibrosis in mice model. Further study of
      mRNA expression of cytokines reveals that depletion of Tregs leads to the
      increased production of Th1-cytokines and decreased production of Th2-cytokine.
      The Flow Cytometry and realtime PCR study show that Treg cells exert the
      modulation function both directly by expressing CTLA-4 at the inflammatory stage,
      and indirectly by secreting increasing amount of IL-10 and TGF-beta during the
      fibrotic stage in silica-induced lung fibrosis. CONCLUSION/SIGNIFICANCE: Our
      study suggests that depletion of Tregs may attenuate the progress of silica
      induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance
      toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function
      of Treg cells may depend on direct mechanism and indirect mechanism during the
      inflammatory stage of silicosis.

PMID- 21072214
TI  - Apolipophorin-III mediates antiplasmodial epithelial responses in Anopheles
      gambiae (G3) mosquitoes.
AB  - BACKGROUND: Apolipophorin-III (ApoLp-III) is known to play an important role in
      lipid transport and innate immunity in lepidopteran insects. However, there is no
      evidence of involvement of ApoLp-IIIs in the immune responses of dipteran insects
      such as Drosophila and mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: We report the
      molecular and functional characterization of An. gambiae apolipophorin-III
      (AgApoLp-III). Mosquito ApoLp-IIIs have diverged extensively from those of
      lepidopteran insects; however, the predicted tertiary structure of AgApoLp-III is
      similar to that of Manduca sexta (tobacco hornworm). We found that AgApoLp-III
      mRNA expression is strongly induced in the midgut of An. gambiae (G3 strain)
      mosquitoes in response to Plasmodium berghei infection. Furthermore,
      immunofluorescence stainings revealed that high levels of AgApoLp-III protein
      accumulate in the cytoplasm of Plasmodium-invaded cells and AgApoLp-III silencing
      increases the intensity of P. berghei infection by five fold. CONCLUSION: There
      are broad differences in the midgut epithelial responses to Plasmodium invasion
      between An. gambiae strains. In the G3 strain of An. gambiae AgApoLp-III
      participates in midgut epithelial defense responses that limit Plasmodium
      infection.

PMID- 21072216
TI  - Up in the air.

PMID- 21072217
TI  - Effects of fibrin-binding oligopeptide on osteopromotion in rabbit calvarial
      defects.
AB  - PURPOSE: Fibronectin (FN) has been shown to stimulate bone regeneration in animal
      models. The aim of this study was to evaluate the capacity of bovine bone mineral
      coated with synthetic oligopeptides to enhance bone regeneration in rabbit
      calvarial defects. METHODS: Oligopeptides including fibrin-binding sequences of
      FN repeats were synthesized on the basis of primary and tertiary human plasma FN
      structures. Peptide coated and uncoated bone minerals were implanted into 10 mm
      calvarial defects in New Zealand white rabbits, and the animals were sacrificed
      at 4 or 8 weeks after surgery. After specimens were prepared, histologic
      examination and histomorphometric analysis were performed. RESULTS: At 4 weeks
      after surgery, the uncoated groups showed a limited amount of osteoid formation
      at the periphery of the defect and the oligopeptide coated groups showed more
      osteoid formation and new bone formation in the center of the defect as well as
      at the periphery. At 8 weeks, both sites showed increased new bone formation.
      However, the difference between the two sites had reduced. CONCLUSIONS: Fibrin
      binding synthetic oligopeptide derived from FN on deproteinized bovine bone
      enhanced new bone formation in rabbit calvarial defects at the early healing
      stage. This result suggests that these oligopeptides can be beneficial in
      reconstructing oral and maxillofacial deformities or in regenerating osseous bone
      defects.

PMID- 21072215
TI  - In vivo deficiency of both C/EBPbeta and C/EBPepsilon results in highly defective
      myeloid differentiation and lack of cytokine response.
AB  - The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved
      in hematopoietic cell development and induction of several inflammatory
      mediators. Here, we generated C/EBPbeta and C/EBPepsilon double-knockout (bbee)
      mice and compared their phenotypes to those of single deficient (bbEE and BBee)
      and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal
      infections and died within 2-3 months. Morphologically, their neutrophils were
      blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone
      marrow cells indicated a significant decrease in the number of myeloid colonies
      of the bbee mice. In addition, the proportion of hematopoietic progenitor cells
      [Lin(-)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly
      increased, reflecting the defective differentiation of the myeloid compartment.
      Furthermore, microarray expression analysis of LPS- and IFNgamma-activated bone
      marrow-derived macrophages from bbee compared to single knockout mice revealed
      decreased expression of essential immune response-related genes and networks,
      including some direct C/EBP-targets such as Marco and Clec4e. Overall, the
      phenotype of the bbee mice is distinct from either the bbEE or BBee mice,
      demonstrating that both transcription factors are crucial for the maturation of
      neutrophils and macrophages, as well as the innate immune system, and can at
      least in part compensate for each other in the single knockout mice.

PMID- 21072218
TI  - Periodontal regeneration capacity of equine particulate bone in canine alveolar
      bone defects.
AB  - PURPOSE: This study was performed to evaluate the periodontal wound healing
      effect of particulate equine bone mineral on canine alveolar bone defects.
      METHODS: Twelve adult male beagle dogs were used as study subjects. The
      mandibular second and fourth premolars were extracted prior to the experimental
      surgery, and the extraction sites were allowed to heal for 8 weeks. After
      periodontal probing, two-walled defects were created at the mesial and distal
      sides of the mandibular third premolars bilaterally, and the defects were filled
      with equine particulate bone with collagen membrane or bovine particulate bone
      with collagen membrane, or collagen membrane alone. The defects without any
      treatment served as negative controls. After probing depth measurement, animals
      were sacrificed at 10, 16, and 24 post-surgery weeks for micro-computed
      tomographic and histomorphometric analysis. RESULTS: The equine particulate bone
      inserted group showed significantly decreased values of probing depth and first
      bone contact compared to the negative control and collagen membrane alone groups
      at weeks 10, 16, and 24 (P < 0.05). There were no significant differences in the
      new cementum length, newly-formed bone area, or newly-formed bone volume between
      equine particulate bone- and bovine particulate bone-inserted groups, both of
      which showed significantly increased values compared to the negative control and
      collagen membrane alone groups (P < 0.05). CONCLUSIONS: Equine particulate bone
      showed significant differences in probing depth, first bone contact, new cementum
      length, newly formed bone area, and bone volume fraction values when compared to
      the negative control and collagen membrane alone groups. There were no
      significant differences between equine and bovine particulate bone substitutes in
      these parameters; therefore, we can conclude that equine particulate bone is
      equivalent to bovine bone for periodontal regeneration.

PMID- 21072219
TI  - Socket preservation using deproteinized horse-derived bone mineral.
AB  - PURPOSE: The healing process following tooth extraction apparently results in a
      pronounced resorption of the alveolar ridge. As a result, the width of alveolar
      ridge is reduced and severe alveolar bone resorption occurs. The purpose of this
      experiment is to clinically and histologically evaluate the results of using
      horse-derived bone mineral for socket preservation. METHODS: The study comprised
      4 patients who were scheduled for extraction as a consequence of severe chronic
      periodontitis or apical lesion. The extraction was followed by socket
      preservation using horse-derived bone minerals. Clinical parameters included
      buccal-palatal width, mid-buccal crest height, and mid-palatal crest height. A
      histologic examination was conducted. RESULTS: The surgical sites healed
      uneventfully. The mean ridge width was 7.75 +/- 2.75 mm at baseline and 7.00 +/-
      2.45 mm at 6 months. The ridge width exhibited no significant difference between
      baseline and 6 months. The mean buccal crest height at baseline was 7.5 +/- 5.20
      mm, and at 6 months, 3.50 +/- 0.58 mm. The mean palatal crest height at baseline
      was 7.75 +/- 3.10 mm, and at 6 months, 5.00 +/- 0.82 mm. There were no
      significant differences between baseline and 6 months regarding buccal and
      palatal crest heights. The amount of newly formed bone was 9.88 +/- 2.90%, the
      amount of graft particles was 42.62 +/- 6.57%, and the amount of soft tissue was
      47.50 +/- 9.28%. CONCLUSIONS: Socket preservation using horse-derived bone
      mineral can effectively maintain ridge dimensions following tooth extraction and
      can promote new bone formation through osteoconductive activities.

PMID- 21072220
TI  - Biological effects of a porcine-derived collagen membrane on intrabony defects.
AB  - PURPOSE: To prolong the degradation time of collagen membranes, various cross
      linking techniques have been developed. For cross-linking, chemicals such as
      formaldehyde and glutaraldehyde are added to collagen membranes, but these
      chemicals could adversely affect surrounding tissues. The aim of this study is to
      evaluate the ability of porous non-chemical cross-linking porcine-derived
      collagen nanofibrous membrane to enhance bone and associated tissue regeneration
      in one-wall intrabony defects in beagle dogs. METHODS: The second and third
      mandibular premolars and the first molars of 2 adult beagles were extracted
      bilaterally and the extraction sites were allowed to heal for 10 weeks. One-wall
      intrabony defects were prepared bilaterally on the mesial and distal side of the
      fourth mandibular premolars. Among eight defects, four defects were not covered
      with membrane as controls and the other four defects were covered with membrane
      as the experimental group. The animals were sacrificed 10 weeks after surgery.
      RESULTS: Wound healing was generally uneventful. For all parameters evaluating
      bone regeneration, the experimental group showed significantly superior results
      compared to the control. In new bone height (NBh), the experimental group
      exhibited a greater mean value than the control (3.04 +/- 0.23 mm/1.57 +/- 0.59,
      P = 0.003). Also, in new bone area (NBa) and new bone volume (NBv), the
      experimental group showed superior results compared to the control (NBa, 34.48 +/
      10.21% vs. 5.09 +/- 5.76%, P = 0.014; and NBv, 28.04 +/- 12.96 vs. 1.55 +/-
      0.57, P = 0.041). On the other hand, for parameters evaluating periodontal tissue
      regeneration, including junctional epithelium migration and new cementum height,
      there were no statistically significant differences between two groups.
      CONCLUSIONS: Within the limitations of this study, this collagen membrane
      enhanced bone regeneration at one-wall intrabony defects. On the other hand, no
      influence of this membrane on periodontal tissue regeneration could be
      ascertained in this study.

PMID- 21072221
TI  - The effect of implant shape and bone preparation on primary stability.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of implant shape
      and bone preparation on the primary stability of the implants using resonance
      frequency analysis. METHODS: Sixty bovine rib blocks were used for soft and hard
      bone models. Each rib block received two types of dental implant fixtures; a
      straight-screw type and tapered-screw type. Final drilling was done at three
      different depths for each implant type; 1 mm under-preparation, standard
      preparation, and 1 mm over-preparation. Immediately after fixture insertion, the
      implant stability quotient (ISQ) was measured for each implant. RESULTS:
      Regardless of the bone type, the ISQ values of the straight-screw type and
      tapered-screw type implants were not significantly different (P > 0.05). Depth of
      bone preparation had no significant effect on the ISQ value of straight-screw
      type implants (P > 0.05). For the tapered-screw type implants, under-preparation
      significantly increased the ISQ value (P < 0.05), whereas overpreparation
      significantly decreased the ISQ value (P < 0.05). CONCLUSIONS: Within the
      limitations of this study, it is concluded that bone density seemed to have a
      prevailing effect over implant shape on primary stability. The primary stability
      of the tapered-screw type implants might be enhanced by delicate surgical
      techniques.

PMID- 21072222
TI  - Marginal bony changes in relation to different vertical positions of dental
      implants.
AB  - PURPOSE: The purpose of this study was to radiographically evaluate marginal bony
      changes in relation to different vertical positions of dental implants. METHODS:
      Two hundred implants placed in 107 patients were examined. The implants were
      classified by the vertical positions of the fixture-abutment connection
      (microgap): 'bone level,' 'above bone level,' or 'below bone level.' Marginal
      bone levels were examined in the radiographs taken immediately after fixture
      insertion, immediately after second-stage surgery, 6 months after prosthesis
      insertion, and 1 year after prosthesis insertion. Radiographic evaluation was
      carried out by measuring the distance between the microgap and the most coronal
      bone-to-implant contact (BIC). RESULTS: Immediately after fixture insertion, the
      distance between the microgap and most coronal BIC was 0.06 +/- 0.68 mm; at
      second surgery, 0.43 +/- 0.83 mm; 6 months after loading, 1.36 +/- 0.56 mm; and 1
      year after loading, 1.53 +/- 0.51 mm (mean +/- SD). All bony changes were
      statistically significant but the difference between the second surgery and the 6
      month loading was greater than between other periods. In the 'below bone level'
      group, the marginal bony change between fixture insertion and 1 year after
      loading was about 2.25 mm, and in the 'bone level' group, 1.47 mm, and in 'above
      bone level' group, 0.89 mm. Therefore, the marginal bony change was smaller than
      other groups in the 'above bone level' group and larger than other groups in the
      'below bone level' group. CONCLUSIONS: Our results demonstrated that marginal
      bony changes occur during the early phase of healing after implant placement.
      These changes are dependent on the vertical positions of implants.

PMID- 21072223
TI  - Clinical case report on treatment of generalized aggressive periodontitis.
AB  - PURPOSE: The purpose of this study was to evaluate the improvement of periodontal
      health of generalized aggressive periodontitis (GAgP) diagnosed patients treated
      with non-surgical periodontal therapy accompanying systemic antibiotics
      administration. METHODS: Two patients with GAgP were chosen for this study.
      Clinical indices were taken and a radiographic examination was performed at the
      baseline of the study and they were treated by periodontal therapy accompanying
      systemic antibiotics administration. Post-surgical visits were scheduled at
      regular intervals to check clinical and radiographic changes. RESULTS: Through
      non-surgical periodontal therapy accompanying systemic antibiotics
      administration, GAgP patients showed decreased probing pocket depth, sulcus
      bleeding index, and increased attachment level and clinical index when comparing
      the initial and six month follow up data. In the six month follow-up radiographic
      examination after non-surgical periodontal therapy, resolution of the bony defect
      was observed. CONCLUSIONS: Non-surgical therapy combined with systemic
      antibiotics administration in GAgP patients is suggested to be an effective
      approach to enhance the periodontal health.

PMID- 21072224
TI  - Trachoma prevalence and associated risk factors in the gambia and Tanzania:
      baseline results of a cluster randomised controlled trial.
AB  - BACKGROUND: Blinding trachoma, caused by ocular infection with Chlamydia
      trachomatis, is targeted for global elimination by 2020. Knowledge of risk
      factors can help target control interventions. METHODOLOGY/PRINCIPAL FINDINGS: As
      part of a cluster randomised controlled trial, we assessed the baseline
      prevalence of, and risk factors for, active trachoma and ocular C. trachomatis
      infection in randomly selected children aged 0-5 years from 48 Gambian and 36
      Tanzanian communities. Both children's eyes were examined according to the World
      Health Organization (WHO) simplified grading system, and an ocular swab was taken
      from each child's right eye and processed by Amplicor polymerase chain reaction
      to test for the presence of C. trachomatis DNA. Prevalence of active trachoma was
      6.7% (335/5033) in The Gambia and 32.3% (1008/3122) in Tanzania. The countries'
      corresponding Amplicor positive prevalences were 0.8% and 21.9%. After
      adjustment, risk factors for follicular trachoma (TF) in both countries were
      ocular or nasal discharge, a low level of household head education, and being
      aged >= 1 year. Additional risk factors in Tanzania were flies on the child's
      face, being Amplicor positive, and crowding (the number of children per
      household). The risk factors for being Amplicor positive in Tanzania were similar
      to those for TF, with the exclusion of flies and crowding. In The Gambia, only
      ocular discharge was associated with being Amplicor positive.
      CONCLUSIONS/SIGNIFICANCE: These results indicate that although the prevalence of
      active trachoma and Amplicor positives were very different between the two
      countries, the risk factors for active trachoma were similar but those for being
      Amplicor positive were different. The lack of an association between being
      Amplicor positive and TF in The Gambia highlights the poor correlation between
      the presence of trachoma clinical signs and evidence of C. trachomatis infection
      in this setting. Only ocular discharge was associated with evidence of C.
      trachomatis DNA in The Gambia, suggesting that at this low endemicity, this may
      be the most important risk factor. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00792922.

PMID- 21072225
TI  - Targeting antibiotics to households for trachoma control.
AB  - BACKGROUND: Mass drug administration (MDA) is part of the current trachoma
      control strategy, but it can be costly and results in many uninfected individuals
      receiving treatment. Here we explore whether alternative, targeted approaches are
      effective antibiotic-sparing strategies. METHODOLOGY/PRINCIPAL FINDINGS: We
      analysed data on the prevalence of ocular infection with Chlamydia trachomatis
      and of active trachoma disease among 4,436 individuals from two communities in
      The Gambia (West Africa) and two communities in Tanzania (East Africa). An age-
      and household-structured mathematical model of transmission was fitted to these
      data using maximum likelihood. The presence of active inflammatory disease as a
      marker of infection in a household was, in general, significantly more sensitive
      (between 79% [95%CI: 60%-92%] and 86% [71%-95%] across the four communities) than
      as a marker of infection in an individual (24% [16%-33%]-66% [56%-76%]). Model
      simulations, under the best fit models for each community, showed that targeting
      treatment to households has the potential to be as effective as and significantly
      more cost-effective than mass treatment when antibiotics are not donated. The
      cost (2007US$) per incident infection averted ranged from 1.5 to 3.1 for MDA,
      from 1.0 to 1.7 for household-targeted treatment assuming equivalent coverage,
      and from 0.4 to 1.7 if household visits increased treatment coverage to 100% in
      selected households. Assuming antibiotics were donated, MDA was predicted to be
      more cost-effective unless opportunity costs incurred by individuals collecting
      antibiotics were included or household visits improved treatment uptake. Limiting
      MDA to children was not as effective in reducing infection as the other
      aforementioned distribution strategies. CONCLUSIONS/SIGNIFICANCE: Our model
      suggests that targeting antibiotics to households with active trachoma has the
      potential to be a cost-effective trachoma control measure, but further work is
      required to assess if costs can be reduced and to what extent the approach can
      increase the treatment coverage of infected individuals compared to MDA in
      different settings.

PMID- 21072226
TI  - Importance of TLR2 on hepatic immune and non-immune cells to attenuate the strong
      inflammatory liver response during Trypanosoma cruzi acute infection.
AB  - BACKGROUND: Toll-like receptors (TLR) and cytokines play a central role in the
      pathogen clearance as well as in pathological processes. Recently, we reported
      that TLR2, TLR4 and TLR9 are differentially modulated in injured livers from
      BALB/c and C57BL/6 (B6) mice during Trypanosoma cruzi infection. However, the
      molecular and cellular mechanisms involved in local immune response remain
      unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate that
      hepatic leukocytes from infected B6 mice produced higher amounts of pro
      inflammatory cytokines than BALB/c mice, whereas IL10 and TGFbeta were only
      released by hepatic leukocytes from BALB/c. Strikingly, a higher expression of
      TLR2 and TLR4 was observed in hepatocytes of infected BALB/c mice. However, in
      infected B6 mice, the strong pro-inflammatory response was associated with a high
      and sustained expression of TLR9 and iNOS in leukocytes and hepatic tissue
      respectively. Additionally, co-expression of gp91- and p47-phox NADPH oxidase
      subunits were detected in liver tissue of infected B6 mice. Notably, the pre
      treatment previous to infection with Pam3CSK4, TLR2-agonist, induced a
      significant reduction of transaminase activity levels and inflammatory foci
      number in livers of infected B6 mice. Moreover, lower pro-inflammatory cytokines
      and increased TGFbeta levels were detected in purified hepatic leukocytes from
      TLR2-agonist pre-treated B6 mice. CONCLUSIONS/SIGNIFICANCE: Our results describe
      some of the main injurious signals involved in liver immune response during the
      T. cruzi acute infection. Additionally we show that the administration of
      Pam3CSk4, previous to infection, can attenuate the exacerbated inflammatory
      response of livers in B6 mice. These results could be useful to understand and
      design novel immune strategies in controlling liver pathologies.

PMID- 21072227
TI  - Role of the gp85/trans-sialidases in Trypanosoma cruzi tissue tropism:
      preferential binding of a conserved peptide motif to the vasculature in vivo.
AB  - BACKGROUND: Transmitted by blood-sucking insects, the unicellular parasite
      Trypanosoma cruzi is the causative agent of Chagas' disease, a malady manifested
      in a variety of symptoms from heart disease to digestive and urinary tract
      dysfunctions. The reasons for such organ preference have been a matter of great
      interest in the field, particularly because the parasite can invade nearly every
      cell line and it can be found in most tissues following an infection. Among the
      molecular factors that contribute to virulence is a large multigene family of
      proteins known as gp85/trans-sialidase, which participates in cell attachment and
      invasion. But whether these proteins also contribute to tissue homing had not yet
      been investigated. Here, a combination of endothelial cell immortalization and
      phage display techniques has been used to investigate the role of gp85/trans
      sialidase in binding to the vasculature. METHODS: Bacteriophage expressing an
      important peptide motif (denominated FLY) common to all gp85/trans-sialidase
      proteins was used as a surrogate to investigate the interaction of this motif
      with the endothelium compartment. For that purpose phage particles were incubated
      with endothelial cells obtained from different organs or injected into mice
      intravenously and the number of phage particles bound to cells or tissues was
      determined. Binding of phages to intermediate filament proteins has also been
      studied. FINDINGS AND CONCLUSIONS: Our data indicate that FLY interacts with the
      endothelium in an organ-dependent manner with significantly higher avidity for
      the heart vasculature. Phage display results also show that FLY interaction with
      intermediate filament proteins is not limited to cytokeratin 18 (CK18), which may
      explain the wide variety of cells infected by the parasite. This is the first
      time that members of the intermediate filaments in general, constituted by a
      large group of ubiquitously expressed proteins, have been implicated in T. cruzi
      cell invasion and tissue homing.

PMID- 21072228
TI  - LAMP for human African trypanosomiasis: a comparative study of detection formats.
AB  - Loop-mediated isothermal amplification (LAMP) is at the forefront of the search
      for innovative diagnostics for human African trypanosomiasis (HAT). Several
      simple endpoint detection methods have been developed for LAMP and here we
      compare four of these: (i) visualization of turbidity; (ii) addition of
      hydroxynaphthol blue before incubation; (iii) addition of calcein with MnCl2
      before incubation and (iv) addition of Quant-iT PicoGreen after incubation. These
      four methods were applied to four LAMP assays for the detection of human African
      trypanosomiasis, including two Trypanozoon specific and two Trypanosoma brucei
      rhodesiense specific reactions using DNA extracted from cryo-preserved procyclic
      form T. b. rhodesiense. A multi-observer study was performed to assess inter
      observer reliability of two of these methods: hydroxynapthol blue and calcein
      with MnCl2, using DNA prepared from blood samples stored on Whatman FTA cards.
      Results showed that hydroxynaphthol blue was the best of the compared methods for
      easy, inexpensive, accurate and reliable interpretation of LAMP assays for HAT.
      Hydroxynapthol blue generates a violet to sky blue colour change that was easy to
      see and was consistently interpreted by independent observers. Visible turbidity
      detection is not possible for all currently available HAT LAMP reactions; Quant
      iT PicoGreen is expensive and addition of calcein with MnCl2 adversely affects
      reaction sensitivity and was unpopular with several observers.

PMID- 21072229
TI  - Health seeking behaviour and utilization of health facilities for schistosomiasis
      related symptoms in ghana.
AB  - BACKGROUND: Schistosomiasis causes long-term illness and significant economic
      burden. Morbidity control through integration within existing health care
      delivery systems is considered a potentially sustainable and cost-effective
      approach, but there is paucity of information about health-seeking behaviour.
      METHODS: A questionnaire-based study involving 2,002 subjects was conducted in
      three regions of Ghana to investigate health-seeking behaviour and utilization of
      health facilities for symptoms related to urinary (blood in urine and painful
      urination) and intestinal schistosomiasis (diarrhea, blood in stool, swollen
      abdomen and abdominal pain). Fever (for malaria) was included for comparison.
      RESULTS: Only 40% of patients with urinary symptoms sought care compared to >70%
      with intestinal symptoms and >90% with fever. Overall, about 20% of
      schistosomiasis-related symptoms were reported to a health facility (hospital or
      clinic), compared to about 30% for fever. Allopathic self-medication was commonly
      practiced as alternative action. Health-care seeking was relatively lower for
      patients with chronic symptoms, but if they took action, they were more likely to
      visit a health facility. In a multivariate logistic regression analysis,
      perceived severity was the main predictor for seeking health care or visiting a
      health facility. Age, socio-economic status, somebody else paying for health
      care, and time for hospital visit occasionally showed a significant impact, but
      no clear trend. The effect of geographic location was less marked, although
      people in the central region, and to a lesser extent the north, were usually less
      inclined to seek health care than people in the south. Perceived quality of
      health facility did not demonstrate impact. CONCLUSION: Perceived severity of the
      disease is the most important determinant of seeking health care or visiting a
      health facility in Ghana. Schistosomiasis control by passive case-finding within
      the regular health care delivery looks promising, but the number not visiting a
      health facility is large and calls for supplementary control options.

PMID- 21072230
TI  - Quantifying the burden of rhodesiense sleeping sickness in Urambo District,
      Tanzania.
AB  - BACKGROUND: Human African trypanosomiasis is a severely neglected vector-borne
      disease that is always fatal if untreated. In Tanzania it is highly focalised and
      of major socio-economic and public health importance in affected communities.
      OBJECTIVES: This study aimed to estimate the public health burden of rhodesiense
      HAT in terms of DALYs and financial costs in a highly disease endemic area of
      Tanzania using hospital records. MATERIALS AND METHODS: Data was obtained from
      143 patients admitted in 2004 for treatment for HAT at Kaliua Health Centre,
      Urambo District. The direct medical and other indirect costs incurred by
      individual patients and by the health services were calculated. DALYs were
      estimated using methods recommended by the Global Burden of Disease Project as
      well as those used in previous rhodesiense HAT estimates assuming HAT under
      reporting of 45%, a figure specific for Tanzania. RESULTS: The DALY estimate for
      HAT in Urambo District with and without age-weighting were 215.7 (95% CI: 155.3
      287.5) and 281.6 (95% CI: 209.1-362.6) respectively. When 45% under-reporting was
      included, the results were 622.5 (95% CI: 155.3-1098.9) and 978.9 (95% CI: 201.1
      1870.8) respectively. The costs of treating 143 patients in terms of admission
      costs, diagnosis, hospitalization and sleeping sickness drugs were estimated at
      US$ 15,514, of which patients themselves paid US$ 3,673 and the health services
      US$ 11,841. The burden in terms of indirect non-medical costs for the 143
      patients was estimated at US$ 9,781. CONCLUSIONS: This study shows that HAT
      imposes a considerable burden on affected rural communities in Tanzania and
      stresses the urgent need for location- and disease-specific burden estimates
      tailored to particular rural settings in countries like Tanzania where a
      considerable number of infectious diseases are prevalent and, due to their focal
      nature, are often concentrated in certain locations where they impose an
      especially high burden.

PMID- 21072231
TI  - A systematic review of the frequency of neurocyticercosis with a focus on people
      with epilepsy.
AB  - BACKGROUND: The objective of this study is to conduct a systematic review of
      studies reporting the frequency of neurocysticercosis (NCC) worldwide.
      METHODS/PRINCIPAL FINDINGS: PubMed, Commonwealth Agricultural Bureau (CAB)
      abstracts and 23 international databases were systematically searched for
      articles published from January 1, 1990 to June 1, 2008. Articles were evaluated
      for inclusion by at least two researchers focusing on study design and methods.
      Data were extracted independently using standardized forms. A random-effects
      binomial model was used to estimate the proportion of NCC among people with
      epilepsy (PWE). Overall, 565 articles were retrieved and 290 (51%) selected for
      further analysis. After a second analytic phase, only 4.5% of articles, all of
      which used neuroimaging for the diagnosis of NCC, were reviewed. Only two
      studies, both from the US, estimated an incidence rate of NCC using hospital
      discharge data. The prevalence of NCC in a random sample of village residents was
      reported from one study where 9.1% of the population harboured brain lesions of
      NCC. The proportion of NCC among different study populations varied widely.
      However, the proportion of NCC in PWE was a lot more consistent. The pooled
      estimate for this population was 29.0% (95%CI: 22.9%-35.5%). These results were
      not sensitive to the inclusion or exclusion of any particular study.
      CONCLUSION/SIGNIFICANCE: Only one study has estimated the prevalence of NCC in a
      random sample of all residents. Hence, the prevalence of NCC worldwide remains
      unknown. However, the pooled estimate for the proportion of NCC among PWE was
      very robust and could be used, in conjunction with estimates of the prevalence
      and incidence of epilepsy, to estimate this component of the burden of NCC in
      endemic areas. The previously recommended guidelines for the diagnostic process
      and for declaring NCC an international reportable disease would improve the
      knowledge on the global frequency of NCC.

PMID- 21072232
TI  - CD8 cells of patients with diffuse cutaneous leishmaniasis display functional
      exhaustion: the latter is reversed, in vitro, by TLR2 agonists.
AB  - Leishmania mexicana (Lm) causes localized (LCL) and diffuse (DCL) cutaneous
      leishmaniasis. DCL patients have a poor cellular immune response leading to
      chronicity. It has been proposed that CD8 T lymphocytes (CD8) play a crucial role
      in infection clearance, although the role of CD8 cytotoxicity in disease control
      has not been elucidated. Lesions of DCL patients have been shown to harbor low
      numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment
      restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led
      us to analyze possible functional differences between CD8 from patients with LCL
      and DCL. We compared IFNgamma production, antigen-specific proliferation, and
      cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO)
      infected with Leishmania mexicana (MOi). Additionally, we analyzed tissue
      biopsies from both groups of patients for evidence of cytotoxicity associated
      with apoptotic cells in the lesions. We found that CD8 cell of DCL patients
      exhibited low cytotoxicity, low antigen-specific proliferation and low IFNgamma
      production when stimulated with MOi, as compared to LCL patients. Additionally,
      DCL patients had significantly less TUNEL+ cells in their lesions. These
      characteristics are similar to cellular "exhaustion" described in chronic
      infections. We intended to restore the functional capacity of CD8 cells of DCL
      patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG) or
      Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNgamma
      production were restored with both stimuli, whereas PD-1 (a molecule associated
      with cellular exhaustion) expression, was reduced. Our work suggests that CD8
      response is associated with control of Lm infection in LCL patients and that
      chronic infection in DCL patients leads to a state of CD8 functional exhaustion,
      which could facilitate disease spread. This is the first report that shows the
      presence of functionally exhausted CD8 T lymphocytes in DCL patients and,
      additionally, that pre-stimulation with TLR2 ligands can restore the effector
      mechanisms of CD8 T lymphocytes from DCL patients against Leishmania mexicana
      infected macrophages.

PMID- 21072233
TI  - Serological evaluation of Mycobacterium ulcerans antigens identified by
      comparative genomics.
AB  - A specific and sensitive serodiagnostic test for Mycobacterium ulcerans infection
      would greatly assist the diagnosis of Buruli ulcer and would also facilitate
      seroepidemiological surveys. By comparative genomics, we identified 45 potential
      M. ulcerans specific proteins, of which we were able to express and purify 33 in
      E. coli. Sera from 30 confirmed Buruli ulcer patients, 24 healthy controls from
      the same endemic region and 30 healthy controls from a non-endemic region in
      Benin were screened for antibody responses to these specific proteins by ELISA.
      Serum IgG responses of Buruli ulcer patients were highly variable, however, seven
      proteins (MUP045, MUP057, MUL_0513, Hsp65, and the polyketide synthase domains
      ER, AT propionate, and KR A) showed a significant difference between patient and
      non-endemic control antibody responses. However, when sera from the healthy
      control subjects living in the same Buruli ulcer endemic area as the patients
      were examined, none of the proteins were able to discriminate between these two
      groups. Nevertheless, six of the seven proteins showed an ability to distinguish
      people living in an endemic area from those in a non-endemic area with an average
      sensitivity of 69% and specificity of 88%, suggesting exposure to M. ulcerans.
      Further validation of these six proteins is now underway to assess their
      suitability for use in Buruli ulcer seroepidemiological studies. Such studies are
      urgently needed to assist efforts to uncover environmental reservoirs and
      understand transmission pathways of the M. ulcerans.

PMID- 21072234
TI  - Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E2
      production in murine macrophages.
AB  - BACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis
      and immune responses. Nevertheless, the role played by this saliva in the
      induction of key elements of inflammatory responses, such as lipid bodies (LB,
      also known as lipid droplets) and eicosanoids, has been poorly investigated. LBs
      are cytoplasmic organelles involved in arachidonic acid metabolism that form
      eicosanoids in response to inflammatory stimuli. In this study, we assessed the
      role of salivary gland sonicate (SGS) from Lutzomyia (L.) longipalpis, a
      Leishmania infantum chagasi vector, in the induction of LBs and eicosanoid
      production by macrophages in vitro and ex vivo. METHODOLOGY/PRINCIPAL FINDINGS:
      Different doses of L. longipalpis SGS were injected into peritoneal cavities of
      C57BL/6 mice. SGS induced increased macrophage and neutrophil recruitment into
      the peritoneal cavity at different time points. Sand fly saliva enhanced PGE2 and
      LTB4 production by harvested peritoneal leukocytes after ex vivo stimulation with
      a calcium ionophore. At three and six hours post-injection, L. longipalpis SGS
      induced more intense LB staining in macrophages, but not in neutrophils, compared
      with mice injected with saline. Moreover, macrophages harvested by peritoneal
      lavage and stimulated with SGS in vitro presented a dose- and time-dependent
      increase in LB numbers, which was correlated with increased PGE2 production.
      Furthermore, COX-2 and PGE-synthase co-localized within the LBs induced by L.
      longipalpis saliva. PGE2 production by macrophages induced by SGS was abrogated
      by treatment with NS-398, a COX-2 inhibitor. Strikingly, SGS triggered ERK-1/2
      and PKC-alpha phosphorylation, and blockage of the ERK-1/2 and PKC-alpha pathways
      inhibited the SGS effect on PGE2 production by macrophages. CONCLUSION: In sum,
      our results show that L. longipalpis saliva induces lipid body formation and PGE2
      production by macrophages ex vivo and in vitro via the ERK-1/2 and PKC-alpha
      signaling pathways. This study provides new insights regarding the
      pharmacological mechanisms whereby L. longipalpis saliva influences the early
      steps of the host's inflammatory response.

PMID- 21072235
TI  - Cost-effectiveness of a chemoprophylactic intervention with single dose
      rifampicin in contacts of new leprosy patients.
AB  - BACKGROUND: With 249,007 new leprosy patients detected globally in 2008, it
      remains necessary to develop new and effective interventions to interrupt the
      transmission of M. leprae. We assessed the economic benefits of single dose
      rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of
      leprosy. METHODS: We conducted a single centre, double blind, cluster randomised,
      placebo controlled trial in northwest Bangladesh between 2002 and 2007, including
      21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a
      single dose of rifampicin or placebo to close contacts, with follow-up for four
      years. The main outcome measure was the development of clinical leprosy. We
      assessed the cost effectiveness by calculating the incremental cost effectiveness
      ratio (ICER) between the standard multidrug therapy (MDT) program with the
      additional chemoprophylaxis intervention versus the standard MDT program only.
      The ICER was expressed in US dollars per prevented leprosy case. FINDINGS:
      Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy
      patients is cost-effective at all contact levels and thereby a cost-effective
      prevention strategy. In total, $6,009 incremental cost was invested and 38
      incremental leprosy cases were prevented, resulting in an ICER of $158 per one
      additional prevented leprosy case. It was the most cost-effective in neighbours
      of neighbours and social contacts (ICER $214), slightly less cost-effective in
      next door neighbours (ICER $497) and least cost-effective among household
      contacts (ICER $856). CONCLUSION: Chemoprophylaxis with single dose rifampicin
      given to contacts of newly diagnosed leprosy patients is a cost-effective
      intervention strategy. Implementation studies are necessary to establish whether
      this intervention is acceptable and feasible in other leprosy endemic areas of
      the world.

PMID- 21072237
TI  - Additional haplogroups of Toxoplasma gondii out of Africa: population structure
      and mouse-virulence of strains from Gabon.
AB  - BACKGROUND: Toxoplasma gondii is found worldwide, but distribution of its
      genotypes as well as clinical expression of human toxoplasmosis varies across the
      continents. Several studies in Europe, North America and South America argued for
      a role of genotypes in the clinical expression of human toxoplasmosis. Genetic
      data concerning T. gondii isolates from Africa are scarce and not sufficient to
      investigate the population structure, a fundamental analysis for a better
      understanding of distribution, circulation, and transmission.
      METHODOLOGY/PRINCIPAL FINDINGS: Seropositive animals originating from urban and
      rural areas in Gabon were analyzed for T. gondii isolation and genotyping. Sixty
      eight isolates, including one mixed infection (69 strains), were obtained by
      bioassay in mice. Genotyping was performed using length polymorphism of 13
      microsatellite markers located on 10 different chromosomes. Results were analyzed
      in terms of population structure by Bayesian statistical modeling, Neighbor
      joining trees reconstruction based on genetic distances, F(ST) and linkage
      disequilibrium. A moderate genetic diversity was detected. Three haplogroups and
      one single genotype clustered 27 genotypes. The majority of strains belonged to
      one haplogroup corresponding to the worldwide Type III. The remaining strains
      were distributed into two haplogroups (Africa 1 and 3) and one single genotype.
      Mouse virulence at isolation was significantly different between haplogroups.
      Africa 1 haplogroup was the most virulent. CONCLUSION: Africa 1 and 3 haplogroups
      were proposed as being new major haplogroups of T. gondii circulating in Africa.
      A possible link with strains circulating in South and Central America is
      discussed. Analysis of population structure demonstrated a local spread within a
      rural area and strain circulation between the main cities of the country. This
      circulation, favored by human activity could lead to genetic exchanges. For the
      first time, key epidemiological questions were addressed for the West African T.
      gondii population, using the high discriminatory power of microsatellite markers,
      thus creating a basis for further epidemiological and clinical investigations.

PMID- 21072236
TI  - Midgut barrier imparts selective resistance to filarial worm infection in Culex
      pipiens pipiens.
AB  - Mosquitoes in the Culex pipiens complex thrive in temperate and tropical regions
      worldwide, and serve as efficient vectors of Bancroftian lymphatic filariasis
      (LF) caused by Wuchereria bancrofti in Asia, Africa, the West Indies, South
      America, and Micronesia. However, members of this mosquito complex do not act as
      natural vectors for Brugian LF caused by Brugia malayi, or for the cat parasite
      B. pahangi, despite their presence in South Asia where these parasites are
      endemic. Previous work with the Iowa strain of Culex pipiens pipiens demonstrates
      that it is equally susceptible to W. bancrofti as is the natural Cx. p. pipiens
      vector in the Nile Delta, however it is refractory to infection with Brugia spp.
      Here we report that the infectivity barrier for Brugia spp. in Cx. p. pipiens is
      the mosquito midgut, which inflicts internal and lethal damage to ingested
      microfilariae. Following per os Brugia exposures, the prevalence of infection is
      significantly lower in Cx. p. pipiens compared to susceptible mosquito controls,
      and differs between parasite species with <50% and <5% of Cx. p. pipiens becoming
      infected with B. pahangi and B. malayi, respectively. When Brugia spp. mf were
      inoculated intrathoracically to bypass the midgut, larvae developed equally well
      as in controls, indicating that, beyond the midgut, Cx. p. pipiens is
      physiologically compatible with Brugia spp. Mf isolated from Cx. p. pipiens
      midguts exhibited compromised motility, and unlike mf derived from blood or
      isolated from the midguts of Ae. aegypti, failed to develop when inoculated
      intrathoracically into susceptible mosquitoes. Together these data strongly
      support the role of the midgut as the primary infection barrier for Brugia spp.
      in Cx. p. pipiens. Examination of parasites recovered from the Cx. p. pipiens
      midgut by vital staining, and those exsheathed with papain, suggest that the
      damage inflicted by the midgut is subcuticular and disrupts internal tissues.
      Microscopic studies of these worms reveal compromised motility and sharp bends in
      the body; and ultrastructurally the presence of many fluid or carbohydrate-filled
      vacuoles in the hypodermis, body wall, and nuclear column. Incubation of Brugia
      mf with Cx. p. pipiens midgut extracts produces similar internal damage
      phenotypes; indicating that the Cx. p. pipiens midgut factor(s) that damage mf in
      vivo are soluble and stable in physiological buffer, and inflict damage on mf in
      vitro.

PMID- 21072238
TI  - Risk factors for death in children with visceral leishmaniasis.
AB  - BACKGROUND: Despite the major public health importance of visceral leishmaniasis
      (VL) in Latin America, well-designed studies to inform diagnosis, treatment and
      control interventions are scarce. Few observational studies address prognostic
      assessment in patients with VL. This study aimed to identify risk factors for
      death in children aged less than 15 years admitted for VL treatment in a referral
      center in northeast Brazil. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective
      cohort, we reviewed 546 records of patients younger than 15 years admitted with
      the diagnosis of VL at the Instituto de Medicina Integral Professor Fernando
      Figueira between May 1996 and June 2006. Age ranged from 4 months to 13.7 years,
      and 275 (50%) were male. There were 57 deaths, with a case-fatality rate of 10%.
      In multivariate logistic regression, the independent predictors of risk of dying
      from VL were (adjusted OR, 95% CI): mucosal bleeding (4.1, 1.3-13.4), jaundice
      (4.4, 1.7-11.2), dyspnea (2.8, 1.2-6.1), suspected or confirmed bacterial
      infections (2.7, 1.2-6.1), neutrophil count <500/mm3 (3.1, 1.4-6.9) and platelet
      count <50,000/mm3 (11.7, 5.4-25.1). A prognostic score was proposed and had
      satisfactory sensitivity (88.7%) and specificity (78.5%).
      CONCLUSIONS/SIGNIFICANCE: Prognostic and severity markers can be useful to inform
      clinical decisions such as whether a child with VL can be safely treated in the
      local healthcare facility or would potentially benefit from transfer to referral
      centers where advanced life support facilities are available. High risk patients
      may benefit from interventions such as early use of extended-spectrum antibiotics
      or transfusion of blood products. These baseline risk-based supportive
      interventions should be assessed in clinical trials.

PMID- 21072239
TI  - The honey bee epigenomes: differential methylation of brain DNA in queens and
      workers.
AB  - In honey bees (Apis mellifera) the behaviorally and reproductively distinct queen
      and worker female castes derive from the same genome as a result of differential
      intake of royal jelly and are implemented in concert with DNA methylation. To
      determine if these very different diet-controlled phenotypes correlate with
      unique brain methylomes, we conducted a study to determine the methyl cytosine
      (mC) distribution in the brains of queens and workers at single-base-pair
      resolution using shotgun bisulfite sequencing technology. The whole-genome
      sequencing was validated by deep 454 sequencing of selected amplicons
      representing eight methylated genes. We found that nearly all mCs are located in
      CpG dinucleotides in the exons of 5,854 genes showing greater sequence
      conservation than non-methylated genes. Over 550 genes show significant
      methylation differences between queens and workers, revealing the intricate
      dynamics of methylation patterns. The distinctiveness of the differentially
      methylated genes is underscored by their intermediate CpG densities relative to
      drastically CpG-depleted methylated genes and to CpG-richer non-methylated genes.
      We find a strong correlation between methylation patterns and splicing sites
      including those that have the potential to generate alternative exons. We
      validate our genome-wide analyses by a detailed examination of two transcript
      variants encoded by one of the differentially methylated genes. The link between
      methylation and splicing is further supported by the differential methylation of
      genes belonging to the histone gene family. We propose that modulation of
      alternative splicing is one mechanism by which DNA methylation could be linked to
      gene regulation in the honey bee. Our study describes a level of molecular
      diversity previously unknown in honey bees that might be important for generating
      phenotypic flexibility not only during development but also in the adult post
      mitotic brain.

PMID- 21072240
TI  - WRAP53 is essential for Cajal body formation and for targeting the survival of
      motor neuron complex to Cajal bodies.
AB  - The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This
      gene also encodes a protein that directs small Cajal body-specific RNAs to Cajal
      bodies. Cajal bodies are nuclear organelles involved in diverse functions such as
      processing ribonucleoproteins important for splicing. Here we identify the WRAP53
      protein as an essential factor for Cajal body maintenance and for directing the
      survival of motor neuron (SMN) complex to Cajal bodies. By RNA interference and
      immunofluorescence we show that Cajal bodies collapse without WRAP53 and that new
      Cajal bodies cannot be formed. By immunoprecipitation we find that WRAP53
      associates with the Cajal body marker coilin, the splicing regulatory protein
      SMN, and the nuclear import receptor importinbeta, and that WRAP53 is essential
      for complex formation between SMN-coilin and SMN-importinbeta. Furthermore,
      depletion of WRAP53 leads to accumulation of SMN in the cytoplasm and prevents
      the SMN complex from reaching Cajal bodies. Thus, WRAP53 mediates the interaction
      between SMN and associated proteins, which is important for nuclear targeting of
      SMN and the subsequent localization of the SMN complex to Cajal bodies. Moreover,
      we detect reduced WRAP53-SMN binding in patients with spinal muscular atrophy,
      which is the leading genetic cause of infant mortality worldwide, caused by
      mutations in SMN1. This suggests that loss of WRAP53-mediated SMN trafficking
      contributes to spinal muscular atrophy.

PMID- 21072241
TI  - Control of transcription by cell size.
AB  - Cell size increases significantly with increasing ploidy. Differences in cell
      size and ploidy are associated with alterations in gene expression, although no
      direct connection has been made between cell size and transcription. Here we show
      that ploidy-associated changes in gene expression reflect transcriptional
      adjustment to a larger cell size, implicating cellular geometry as a key
      parameter in gene regulation. Using RNA-seq, we identified genes whose expression
      was altered in a tetraploid as compared with the isogenic haploid. A significant
      fraction of these genes encode cell surface proteins, suggesting an effect of the
      enlarged cell size on the differential regulation of these genes. To test this
      hypothesis, we examined expression of these genes in haploid mutants that also
      produce enlarged size. Surprisingly, many genes differentially regulated in the
      tetraploid are identically regulated in the enlarged haploids, and the magnitude
      of change in gene expression correlates with the degree of size enlargement.
      These results indicate a causal relationship between cell size and transcription,
      with a size-sensing mechanism that alters transcription in response to size. The
      genes responding to cell size are enriched for those regulated by two mitogen
      activated protein kinase pathways, and components in those pathways were found to
      mediate size-dependent gene regulation. Transcriptional adjustment to enlarged
      cell size could underlie other cellular changes associated with polyploidy. The
      causal relationship between cell size and transcription suggests that cell size
      homeostasis serves a regulatory role in transcriptome maintenance.

PMID- 21072242
TI  - Microglial interactions with synapses are modulated by visual experience.
AB  - Microglia are the immune cells of the brain. In the absence of pathological
      insult, their highly motile processes continually survey the brain parenchyma and
      transiently contact synaptic elements. Aside from monitoring, their physiological
      roles at synapses are not known. To gain insight into possible roles of microglia
      in the modification of synaptic structures, we used immunocytochemical electron
      microscopy, serial section electron microscopy with three-dimensional
      reconstructions, and two-photon in vivo imaging to characterize microglial
      interactions with synapses during normal and altered sensory experience, in the
      visual cortex of juvenile mice. During normal visual experience, most microglial
      processes displayed direct apposition with multiple synapse-associated elements,
      including synaptic clefts. Microglial processes were also distinctively
      surrounded by pockets of extracellular space. In terms of dynamics, microglial
      processes localized to the vicinity of small and transiently growing dendritic
      spines, which were typically lost over 2 d. When experience was manipulated
      through light deprivation and reexposure, microglial processes changed their
      morphology, showed altered distributions of extracellular space, displayed
      phagocytic structures, apposed synaptic clefts more frequently, and enveloped
      synapse-associated elements more extensively. While light deprivation induced
      microglia to become less motile and changed their preference of localization to
      the vicinity of a subset of larger dendritic spines that persistently shrank,
      light reexposure reversed these behaviors. Taken together, these findings reveal
      different modalities of microglial interactions with synapses that are subtly
      altered by sensory experience. These findings suggest that microglia may actively
      contribute to the experience-dependent modification or elimination of a specific
      subset of synapses in the healthy brain.

PMID- 21072243
TI  - Epigenetics of royalty.

PMID- 21072244
TI  - Doctors and drug companies: still cozy after all these years.
AB  - Geoff Spurling and colleagues report findings of a systematic review looking at
      the relationship between exposure to promotional material from pharmaceutical
      companies and the quality, quantity, and cost of prescribing. They fail to find
      evidence of improvements in prescribing after exposure, and find some evidence of
      an association with higher prescribing frequency, higher costs, or lower
      prescribing quality.

PMID- 21072245
TI  - Why do evaluations of eHealth programs fail? An alternative set of guiding
      principles.

PMID- 21072247
TI  - Use of an insulating mask for controlling anisotropy in multilayer electrospun
      scaffolds for tissue engineering.
AB  - Tissue engineering of various musculoskeletal or cardiovascular tissues requires
      scaffolds with controllable mechanical anisotropy. However, native tissues also
      exhibit significant inhomogeneity in their mechanical properties, and the
      principal axes of anisotropy may vary with site or depth from the tissue surface.
      Thus, techniques to produce multilayered biomaterial scaffolds with controllable
      anisotropy may provide improved biomimetic properties for functional tissue
      replacements. In this study, poly(epsilon-caprolactone) scaffolds were
      electrospun onto a collecting electrode that was partially covered by rectangular
      or square shaped insulating masks. The use of a rectangular mask resulted in
      aligned scaffolds that were significantly stiffer in tension in the axial
      direction than the transverse direction at 0 strain (22.9 +/- 1.3 MPa axial, 16.1
      +/- 0.9 MPa transverse), and at 0.1 strain (4.8 +/- 0.3 MPa axial, 3.5 +/- 0.2
      MPa transverse). The unaligned scaffolds, produced using a square mask, did not
      show this anisotropy, with similar stiffness in the axial and transverse
      directions at 0 strain (19.7 +/- 1.4 MPa axial, 20.8 +/- 1.3 MPa transverse) and
      0.1 strain (4.4 +/- 0.2 MPa axial, 4.6 +/- 0.3 MPa, transverse). Aligned
      scaffolds also induced alignment of adipose stem cells near the expected axis on
      aligned scaffolds (0.015 +/- 0.056 rad), while on the unaligned scaffolds, their
      orientation showed more variation and was not along the expected axis (1.005 +/-
      0.225 rad). This method provides a novel means of creating multilayered
      electrospun scaffolds with controlled anisotropy for each layer, potentially
      providing a means to mimic the complex mechanical properties of various native
      tissues.

PMID- 21072248
TI  - Tissue-engineered fibrin scaffolds containing neural progenitors enhance
      functional recovery in a subacute model of SCI.
AB  - Two recurring problems with stem/neural progenitor cell (NPC) transplantation
      therapies for spinal cord injury (SCI) are poor cell survival and uncontrolled
      cell differentiation. The current study evaluated the viability and
      differentiation of embryonic stem cell-derived neural progenitor cells (ESNPCs)
      transplanted within fibrin scaffolds containing growth factors (GFs) and a
      heparin-binding delivery system (HBDS) to enhance cell survival and direct
      differentiation into neurons. Mouse ESNPCs were generated from mouse embryonic
      stem cells (ESCs) using a 4-/4+ retinoic acid (RA) induction protocol that
      resulted in a population of cells that was 70% nestin positive NPCs. The ESNPCs
      were transplanted directly into a rat subacute dorsal hemisection lesion SCI
      model. ESNPCs were either encapsulated in a fibrin scaffold; encapsulated in
      fibrin containing the HBDS, neurotrophin-3 (NT-3) and platelet derived growth
      factor (PDGF-AA); or encapsulated in fibrin scaffolds with NT-3 and PDGF-AA
      without the HBDS. We report that the combination of GFs and fibrin scaffold
      (without HBDS) enhanced the total number of ESNPCs present in the treated spinal
      cords and increased the number of ESNPC-derived NeuN positive neurons 8 weeks
      after transplantation. All experimental groups treated with ESNPCs exhibited an
      increase in behavioral function 4 weeks after transplantation. In a subset of
      animals, the ESNPCs over-proliferated as evidenced by SSEA-1 positive/Ki67
      positive ESCs found at 4 and 8 weeks. These results demonstrate the potential of
      tissue-engineered fibrin scaffolds to enhance the survival of NPCs and highlight
      the need to purify cell populations used in therapies for SCI.

PMID- 21072249
TI  - Tracking Cholera in Coastal Regions using Satellite Observations.
AB  - Cholera remains a significant health threat across the globe. The pattern and
      magnitude of the seven global pandemics suggest that cholera outbreaks primarily
      originate in coastal regions and then spread inland through secondary means.
      Cholera bacteria show strong association with plankton abundance in coastal
      ecosystems. This review study investigates relationship(s) between cholera
      incidence and coastal processes and explores utility of using remote sensing data
      to track coastal plankton blooms, using chlorophyll as a surrogate variable for
      plankton abundance, and subsequent cholera outbreaks. Most studies over the last
      several decades have primarily focused on the microbiological and epidemiological
      understanding of cholera outbreaks. Accurate identification and mechanistic
      understanding of large scale climatic, geophysical and oceanic processes
      governing cholera-chlorophyll relationship is important for developing cholera
      prediction models. Development of a holistic understanding of these processes
      requires long and reliable chlorophyll dataset(s), which are beginning to be
      available through satellites. We have presented a schematic pathway and a
      modeling framework that relate cholera with various hydroclimatic and oceanic
      variables for understanding disease dynamics using latest advances in remote
      sensing. Satellite data, with its unprecedented spatial and temporal coverage,
      have potentials to monitor coastal processes and track cholera outbreaks in
      endemic regions.

PMID- 21072250
TI  - Disseminating Effective Community Prevention Practices: Opportunities for Social
      Work Education.
AB  - In the United States about 17% of adolescents meet diagnostic criteria for
      mental, emotional, and behavioral disorders. Six million young people receive
      treatment services annually for mental, emotional, or behavioral problems. These
      problems affect 1 in 5 families and cost $247 million annually (O'Connell, Boat,
      & Warner, 2009). Some strategies for preventing mental, emotional, and behavioral
      disorders in young people have been developed, tested, and found to be effective
      in preventing the onset, persistence, and severity of psychological disorders,
      drug abuse, and delinquency. Unfortunately, tested and effective prevention
      policies, programs, and practices are not widely used (O'Connell, Boat, & Warner,
      2009). This paper highlights recent advances in prevention science and describes
      some opportunities and challenges in advancing the use of science-based
      prevention in communities. The chapter concludes by exploring the potential role
      of social work education in developing a workforce ready to increase community
      access to effective prevention strategies.

PMID- 21072246
TI  - Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for
      seasonal influenza: a randomized placebo-controlled trial.
AB  - BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing
      the time to alleviation of symptoms in outpatients with seasonal influenza. The
      objective of this study was to compare the short-term virological efficacy of
      oseltamivir-zanamivir combination versus each monotherapy plus placebo. METHODS
      AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general
      practitioners throughout France during the 2008-2009 seasonal influenza epidemic.
      Patients, general practitioners, and outcome assessors were all blinded to
      treatment assignment. Adult outpatients presenting influenza-like illness for
      less than 36 hours and a positive influenza A rapid test diagnosis were
      randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by
      inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir
      plus oral placebo (Z). Treatment efficacy was assessed virologically according to
      the proportion of patients with nasal influenza reverse transcription (RT)-PCR
      below 200 copies genome equivalent (cgeq)/ul at day 2 (primary outcome), and
      clinically to the time to alleviation of symptoms until day 14. Overall 541
      patients (of the 900 planned) were included (OZ,  =192; O, n=176; Z, n=173), 49%
      male, mean age 39 years. In the intention-to-treat analysis conducted in the 447
      patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n=157), O
      (n=141), and Z (n=149) arms had RT-PCR<200 cgeq/ul (-13.0%, 95% confidence
      interval [CI] -23.1 to -2.9, p=0.025; +12.3%, 95% CI 2.39-22.2, p=0.028 for OZ/O
      and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49,
      and 1.68 log(10) cgeq/ul (p=0.060, p=0.016 for OZ/O and OZ/Z). Median time to
      alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0-4.0,
      p=0.018; +0.0, 95% CI -3.0 to 3.0, p=0.960 for OZ/O and OZ/Z). Four severe
      adverse events were observed. Nausea and/or vomiting tended to be more frequent
      in the combination arm (OZ, n=13; O, n=4; and Z, n=5 patients, respectively).
      CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the
      oseltamivir-zanamivir combination appeared less effective than oseltamivir
      monotherapy, and not significantly more effective than zanamivir monotherapy.
      Despite the theoretical potential for the reduction of the emergence of antiviral
      resistance, the lower effectiveness of this combination calls for caution in its
      use in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.govNCT00799760.

PMID- 21072251
TI  - Posttraumatic distress and the presence of posttraumatic growth and meaning in
      life: Experiential avoidance as a moderator.
AB  - Existing models of trauma suggest that for recovery to occur, trauma related cues
      and emotions require awareness and openness while survivors continue committing
      action toward valued life aims (other than regulating emotions). Based on this
      theoretical framework, an unwillingness to be in contact with distressing
      thoughts and feelings (experiential avoidance) might operate together with
      posttraumatic distress to predict when people find benefits and meaning in the
      aftermath of trauma. We hypothesized that people reporting posttraumatic distress
      and less reliance on experiential avoidance would report greater posttraumatic
      growth and meaning in life compared with other trauma survivors. We administered
      questionnaires to 176 college students reporting at least one traumatic event.
      Results supported these moderation models. This is the fourth study (with
      different samples, measures, and methodologies) to provide evidence that a
      combination of excessive anxiety and a heavy reliance on experiential avoidance
      leads to attenuated well-being. We discuss the implications for understanding
      heterogeneous trauma reactions.

PMID- 21072252
TI  - UNDERSTANDING STRUCTURAL EFFECTS OF MULTIPOLE MOMENTS ON AQUEOUS SOLVATION OF
      IONS USING THE SOFT-STICKY DIPOLE-QUADRUPOLE-OCTUPOLE WATER MODEL.
AB  - The effects of water multipole moments on the aqueous solvation of ions were
      determined in Monte Carlo simulations using soft-sticky dipole-quadrupole
      octupole (SSDQO) water. Water molecules formed linear hydrogen bonds to Cl(-)
      using the new SSDQO1 parameters, similar to multi-site models. However, the
      dipole vector was tilted rather than parallel to the oxygen-Na(+) internuclear
      vector as in most multi-site model, while experiment and ab initio molecular
      dynamics simulations generally indicate a range of values between tilted and
      parallel. By varying the multipoles in SSDQO, the octupole was found to determine
      the orientation around Na(+). Moreover, analysis of the multipoles of more
      conventional models is predictive of their performance as solvents.

PMID- 21072253
TI  - Photopolymerized Thiol-Ene Systems as Shape Memory Polymers.
AB  - In this study we introduce the use of thiol-ene photopolymers as shape memory
      polymer systems. The thiol-ene polymer networks are compared to a commonly
      utilized acrylic shape memory polymer and shown to have significantly improved
      properties for two different thiol-ene based polymer formulations. Using
      thermomechanical and mechanical analysis, we demonstrate that thiol-ene based
      shape memory polymer systems have comparable thermomechanical properties while
      also exhibiting a number of advantageous properties due to the thiol-ene
      polymerization mechanism which results in the formation of a homogenous polymer
      network with low shrinkage stress and negligible oxygen inhibition. The resulting
      thiol-ene shape memory polymer systems are tough and flexible as compared to the
      acrylic counterparts. The polymers evaluated in this study were engineered to
      have a glass transition temperature between 30 and 40  degrees C, exhibited free
      strain recovery of greater than 96% and constrained stress recovery of 100%. The
      thiol-ene polymers exhibited excellent shape fixity and a rapid and distinct
      shape memory actuation response.

PMID- 21072254
TI  - COMPLEMENTARY THERAPY USE AMONG RACIAL/ETHNIC GROUPS.

PMID- 21072255
TI  - Solvation of Glucose, Trehalose, and Sucrose by the Soft Sticky Dipole-Quadrupole
      Octupole Water Model.
AB  - Water structure around sugars modeled by partial charges is compared for soft
      sticky dipole-quadrupole-octupole (SSDQO), a fast single-site multipole model,
      and commonly used multi-site models in Monte Carlo simulations. Radial
      distribution functions and coordination numbers of all the models indicate
      similar hydration by hydrogen-bond donor and acceptor waters. However, the new
      optimized SSDQO1 parameters as well as TIP4P-Ew and TIP5P predict a "lone-pair"
      orientation for the water accepting the sugar hydroxyl hydrogen bond that is more
      consistent with the limited experimental data than the "dipole" orientation in
      SPC/E, which has important implications for studies of the cryoprotectant
      properties of sugars.

PMID- 21072256
TI  - Mechanisms underlying mycobacterial infections.

PMID- 21072257
TI  - Systems biology approaches to understanding mycobacterial survival mechanisms.
AB  - The advent of high-throughput platforms for the interrogation of biological
      systems at the cellular and molecular level have allowed living cells to be
      observed and understood at a hitherto unprecedented level of detail and have
      enabled the construction of comprehensive, predictive in silico models. Here, we
      review the application of such high-throughput, systems-biological techniques to
      mycobacteria-specifically to the pernicious human pathogen Mycobacterium
      tuberculosis (MTb) and its ability to survive in human hosts. We discuss the
      development and application of transcriptomic, proteomic, regulomic, and
      metabolomic techniques for MTb as well as the development and application of
      genome-scale in silico models. Thus far, systems-biological approaches have
      largely focused on in vitro models of MTb growth; reliably extending these
      approaches to in vivo conditions relevant to infection is a significant challenge
      for the future that holds the ultimate promise of novel chemotherapeutic
      interventions.

PMID- 21072258
TI  - Interleukin-4, Oxidative Stress, Vascular Inflammation and Atherosclerosis.
AB  - The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been
      implicated in the initiation and progression of atherosclerosis. In fact,
      inflammatory responses in vascular endothelium are primarily regulated through
      oxidative stress-mediated signaling pathways leading to overexpression of pro
      inflammatory mediators. Enhanced expression of cytokines, chemokines and adhesion
      molecules in endothelial cells and their close interactions facilitate recruiting
      and adhering blood leukocytes to vessel wall, and subsequently stimulate
      transendothelial migration, which are thought to be critical early pathologic
      events in atherogenesis. Although interleukin-4 (IL-4) was traditionally
      considered as an anti-inflammatory cytokine, recent in vitro and in vivo studies
      have provided robust evidence that IL-4 exerts pro-inflammatory effects on
      vascular endothelium and may play a critical role in the development of
      atherosclerosis. The cellular and molecular mechanisms responsible for IL-4
      induced atherosclerosis, however, remain largely unknown. The present review
      focuses on the distinct sources of IL-4-mediated reactive oxygen species (ROS)
      generation as well as the pivotal role of ROS in IL-4-induced vascular
      inflammation. These studies will provide novel insights into a clear delineation
      of the oxidative mechanisms of IL-4-mediated stimulation of vascular inflammation
      and subsequent development of atherosclerosis. It will also contribute to novel
      therapeutic approaches for atherosclerosis specifically targeted against pro
      oxidative and pro-inflammatory pathways in vascular endothelium.

PMID- 21072259
TI  - Emotion Knowledge, Social Competence, and Behavior Problems in Childhood and
      Adolescence: A Meta-Analytic Review.
AB  - The present meta-analytic review examined the magnitude of the relation between
      discrete emotion knowledge and three of its most commonly studied correlates in
      childhood and adolescence: social competence, internalizing problems, and
      externalizing problems. Emotion knowledge demonstrated small to medium-sized
      relations with each correlate. Moderators of effect size were also examined and
      included multiple sample and methodological characteristics. Using random effects
      models, significant moderators of effect size for relations between emotion
      knowledge and externalizing problems included sample recruitment, sample age, and
      the source of externalizing problems ratings. Moderators of effect size were not
      found for emotion knowledge and social competence, and the effect sizes across
      samples for emotion knowledge and internalizing problems were homogeneous.
      Results highlight the relatively consistent yet modest relations between emotion
      knowledge and its correlates. Implications for applied research and new
      directions for research on emotion knowledge using innovative methods are
      discussed.

PMID- 21072261
TI  - Targeting diphtheria toxin and TNF alpha expression in ovarian tumors using the
      H19 regulatory sequences.
AB  - BACKGROUND: There are currently no effective therapies for the treatment of
      ovarian cancer ascites fluid (OCAF). H19 is an RNA oncofetal gene that is present
      at high levels in human cancer tissues (ovarian cancer and OCAF among them),
      while existing at a nearly undetectable level in the surrounding normal tissue.
      There is evidence for a synergistic effect in cell cytotoxicity mediated by
      TNFalpha and diphtheria toxin in sensitive and resistant human ovarian tumor cell
      line. Thus, we tested the cytotoxic effect of TNF-alpha cytokine, together with
      the diphtheria toxin, in the therapy of ovarian cancer. METHODS: The therapeutic
      potential of toxin vectors carrying the DT-A gene alone (pH19-DTA), or in
      combination with the TNF-alpha gene (pH19-TNF-DTA), driven by H19 regulatory
      sequences were tested in ovarian carcinoma cell lines and in a heterotopic
      ovarian cancer model. RESULTS: The toxin vectors showed a high killing capacity
      when transfected into different ovarian cancer cell lines. In addition,
      intratumoral injection of the toxin vector into ectopically developed tumors
      caused 40% inhibition of tumor growth. The killing effect after injection of pH19
      TNF-DTA plasmid into ectopically developed tumors was significantly higher than
      that showed by the pH19-DTA plasmid alone, particularly in diphtheria toxin and
      TNF resistant tumors. CONCLUSIONS: These observations may be the first step
      towards a major breakthrough in the treatment of human ovarian cancer. It should
      enable us to identify likely non-responders in advance, and to treat patients who
      are resistant to all known therapies, thereby avoiding treatment failure coupled
      with unnecessary suffering and cost.

PMID- 21072263
TI  - Characterization of a necrotizing enterocolitis model in newborn mice.
AB  - BACKGROUND: Necrotizingenterocolitis (NEC) is a major health concern for
      premature infants and its patho-genesis remains poorly understood. The current
      mouse NEC model has not well been characterized. OBJECTIVES: In this study, we
      develop a simple mouse model of NEC and determine the role of several factors
      modulating human NEC (i.e., breast milk, birth weight, cesarean section and
      bacteria) on intestinal injury. METHODS: In a first experiment, pups born
      naturally and dam fed for <12 hours were gavaged with adult commensal bacteria or
      E. Fecalis, and exposed to hypoxia-cold stress-formula feeding, and compared with
      controls without bacteria inoculation. 72-hour mortality was recorded, and small
      intestines were examined histologically. In a second experiment, we compared the
      incidence of NEC in mice dam fed for <12 hours to those dam fed for 12 to 24
      hours or delivered by cesarean section prior to being submitted to the NEC
      protocol. RESULTS: In pups inoculated with 10(7) CFU of a standardized
      preparation of adult commensal bacteria or 10(5) CFU of E. Fecalis, the incidence
      of severe NEC (>grade 2) was 70% and 37% respectively vs 6% in the controls (no
      bacteria)(p<0.05). In pups dam fed for 12 to 24 hours, NEC incidence was 44(+/
      12)% lower vs those dam fed less than 12 hours (p<0.05). We did not find any
      difference in the NEC incidence between naturally-born pups dam fed for less than
      12 hours and these born by cesarean section. The incidence of severe NEC was
      higher in pups with low birth weight. CONCLUSIONS: we have simplified and
      characterized a neonatal mouse NEC model that shares several risk factors with
      human NEC. Now that transgenic mice are available, this model will be useful to
      study the role played by specific proteins in vivo in NEC development.

PMID- 21072260
TI  - Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the
      art.
AB  - Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in all
      tissues, as part of the perivascular population. As multipotent cells, MSCs can
      differentiate into different tissues originating from mesoderm ranging from bone
      and cartilage, to cardiac muscle. MSCs are an excellent candidate for cell
      therapy because they are easily accessible, their isolation is straightforward,
      they can be bio-preserved with minimal loss of potency, and they have shown no
      adverse reactions to allogeneic versus autologous MSCs transplants. Therefore,
      MSCs are being explored to regenerate damaged tissue and treat inflammation,
      resulting from cardiovascular disease and myo-cardial infarction (MI), brain and
      spinal cord injury, stroke, diabetes, cartilage and bone injury, Crohn's disease
      and graft versus host disease (GvHD). Most of the application and clinical trials
      involve MSCs from bone marrow (BMMSCs). Transplantation of MSCs from bone marrow
      is considered safe and has been widely tested in clinical trials of
      cardiovascular, neurological, and immunological disease with encouraging results.
      There are examples of MSCs utilization in the repair of kidney, muscle and lung.
      The cells were also found to promote angiogenesis, and were used in chronic skin
      wound treatment. Recent studies involve also mesenchymal stem cell transplant
      from umbilical cord (UCMSCt). One of these demonstrate that UCMSCt may improve
      symptoms and biochemical values in patients with severe refractory systemic lupus
      erythematosus (SLE), and therefore this source of MSCs need deeper studies and
      require more attention. However, also if there are 79 registered clinical trial
      sites for evaluating MSC therapy throughout the world, it is still a long way to
      go before using these cells as a routinely applied therapy in clinics.

PMID- 21072262
TI  - Peroxisome proliferator activated receptor-gamma and traumatic brain injury.
AB  - Traumatic brain injury (TBI) represents a major health care problem and a
      significant socioeconomic challenge worldwide. No specific therapy for TBI is
      available. The peroxisome proliferator activated receptor-gamma (PPAR-gamma)
      belongs to the nuclear receptor superfamily. Although PPAR-gamma was originally
      characterized in adipose tissue as a regulator of lipid and glucose metabolism,
      recent studies showed that PPAR-gamma is present in most cell types and plays a
      central role in the regulation of adipogenesis, glucose homeostasis, cellular
      differentiation, apoptosis and inflammation. Here, we reviewed the current
      literature on the molecular mechanisms of PPAR-gamma-related neuroprotection
      after TBI. Growing evidence has indicated that the beneficial effects of PPAR
      gamma activation in TBI appear to be mediated through downregulation of
      inflammatory responses, reduction of oxidative stress, inhibition of apoptosis,
      and promotion of neurogenesis. A thorough understanding of the PPAR-gamma pathway
      will be critical to the development of therapeutic interventions for the
      treatment of patients with TBI.

PMID- 21072264
TI  - Differential fatty acid profile in adipose and non-adipose tissues in obese mice.
AB  - Obesity is a metabolic disease characterized by chronic inflammation. Early
      studies indicated that adipose tissue from obese mice contains more saturated
      fatty acids and that the saturated fatty acids activate TLR4-mediated
      inflammatory signaling, which contributes to inflammation in adipose tissue. In
      this study, we determined fatty acid profile in non-adipose tissues from obese
      (db/db) mice and compared with that from lean mice. Unexpectedly, in contrast to
      a significant increase in saturated and decrease in unsaturated fatty acid in
      adipose tissue from obese mice, the non-adipose tissues from obese mice exhibited
      a significant decrease in saturated and increase in unsaturated fatty acid
      compared with that from lean mice. The liver from obese mice had a 15% and 32%
      decrease in palmitic acid and stearic acid, and a 20% increase in linoleic acid;
      the spleen had a 32% and 60% decrease in palmitic acid and stearic acid, and a
      70% and 50% increase in oleic acid and linoleic acid; and the pancreas had a 50%
      and 75% decrease in palmitic acid and stearic acid, and a 130% and 113% increase
      in oleic acid and linoleic acid. These data suggest that, different from adipose
      tissue where elevated saturated fatty acids contributes to inflammation, fatty
      acids per se in non-adipose tissues such as liver, spleen and pancreas may not
      contribute to inflammatory responses in obese mice.

PMID- 21072265
TI  - Growth and cell-division in extensive (XDR) and extremely drug resistant (XXDR)
      tuberculosis strains: transmission and atomic force observation.
AB  - The ultra-structure of Mycobacterium tuberculosis (MTB) was examined by
      transmission electronic (TEM)) and atomic force microscopy (AFM). The study was
      performed to describe the morphology of susceptible, multidrug-resistant (MDR),
      extensively drug-resistant (XDR) and extremely drug-resistant tuberculosis
      isolates (XXDR-TB) during their exponential growth phase. Four types of cell
      division were observed and described. While three of them (symmetrical,
      asymmetrical and branching type) occurred in all isolates studied, the fourth one
      (adapted type) was seen only in XDR and XXDR-TB bacilli. In the fourth type of
      cell division, a rod shaped mother cell produced a small round shape bacillus
      (0.3-0.5 MUm). These round cells were different from buds or polar division, but
      similar to terminal endospores without showing the typing heat resistance. Based
      on the present observation, we suggest that XDR-and XXDR-TB bacilli accommodate
      changes helping them to overcome the hostile environment. Viewed under AFM, the
      other frequently detected shapes in MTB isolates were oval, V, Y and multi
      branching filaments. These shape variation confirmed pleomorphic phenomena in MTB
      populations and the specific features of pan-resistant strains.

PMID- 21072266
TI  - Selective induction of cell adhesion molecules by proinflammatory mediators in
      human cardiac microvascular endothelial cells in culture.
AB  - Pro-inflammatory mediators can dramatically alter many responses of cultured
      endothelial cells in vitro, which are relevant to understanding the role played
      by the endothelium in inflammation in vivo. The aim of this study was to
      determine the ability of a comprehensive array of pro-inflammatory stimuli to
      modulate Cell Adhesion Molecule (CAM) expression in cultures of human
      microvascular cardiac endothelial cells (HMVEC.c). Cell ELISA, immunocy
      tochemistry and flow cytometry were used to measure the CAM expressions in
      HMVEC.c in response to interleukins, TNF-alpha and LPS. Passage matched HMVEC.c
      from different donors showed different CAM expression profiles, confirming
      inherent variability in endothelial cells. Endothelial cells from different parts
      of the vasculature are exposed to different cytokines and thus different protein
      expression profiles. A thorough understanding of these innate differences in
      expression pattern of the microvasculatures of cardiac tissues might allow us the
      opportunity to target these tissues selectively.

PMID- 21072267
TI  - Transforming growth factor-beta inhibition attenuates pulmonary arterial
      hypertension in rats.
AB  - The role of transforming growth factor-beta in the pathogenesis of pulmonary
      arterial hypertension is unclear. We examined the effects of T9429, an antibody
      against transforming growth factor-beta receptors, on hemodynamic, histological
      and functional parameters in the rat model of monocrotaline-induced pulmonary
      hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar
      rats, T9429 (0.1mg/kg daily) was administered intraperito-neally in 19 rats
      (268+/-10g) via an osmotic mini-pump for 7 days. One week thereafter, right
      ventricular systolic pressure, pulmonary vascular remodeling and exercise
      tolerance were evaluated. Compared to the monocrotaline group (25.5+/-1.9mmHg),
      right ventricular systolic pressure was lower (p=0.0014) in the
      monocrotaline+antibody group (18.4+/-0.8mmHg). This was translated into
      attenuated right ventricular hypertrophy (p=0.0063) and longer (p=0.0155)
      exercise duration (2.08+/-0.29min versus 6.19+/-1.02min). Pulmonary arterial wall
      thickness (in vessels 50 -200MUm) was comparable between the two groups, but the
      monocrotaline+antibody group displayed lower number (p<0.0001) of pre-capillary
      arterioles (<50MUm, in 20 randomly selected fields) with a muscularized media
      (23.33+/-3.15 versus 6.64+/-0.75). Our results suggest that transforming growth
      factor-beta receptor blockade improves vascular remodeling and attenuates
      pulmonary hypertension, a finding with potential therapeutic implications.

PMID- 21072268
TI  - A novel colonic anastomosis technique involving fixed polyglycolic acid mesh.
AB  - BACKGROUND: Polyglycolic acid mesh (PAM) reinforcement of colonic anastomoses
      were evaluated. METHODS: Twenty female albino rabbits were divided into two
      groups. Each rabbit underwent segmental colonic resection with single-layer
      anastomosis. In one group of rabbits, PAM of length equal to the circumference of
      the anastomosis was applied. Rabbits were sacrificed on postoperative day 10 and
      peritoneal adhesions, anastomosis burst pressure, and anastomosis
      histopathological characteristics were evaluated. RESULTS: The average burst
      pressure for the control and PAM groups was 149+/-15.95 mmHgand 224+/-124.5 mmHg,
      respectively (p=0.578). All control anastomoses burst, whereas only five (50%)
      PAM anastomoses burst (p<0.03). There was no anastomotic leakage in the control
      group, whereas three PAM group anastomoses leaked (p=0.210). The collagen fiber
      density and amount of neovascularization were lower in the PAM than the control
      group (p=0.001 and p=0.002, respectively). The average peritoneal adhesion value
      was 1.6+/-0.51 in the control group and 2.9+/-0.31 in the PAM group (p<0.0001).
      CONCLUSION: The new fixed PAM-reinforced anastomosis technique resulted in an
      increased risk of anastomosis leakage and peritoneal adhesion, but also higher in
      non-burst anastomoses.

PMID- 21072269
TI  - Editorial board 2010.

PMID- 21072270
TI  - Once-monthly risedronate for postmenopausal osteoporosis.
AB  - Bisphosphonates are the mainstay of treatment for postmenopausal women with
      osteoporosis. Despite numerous clinical trials documenting efficacy,
      tolerability, and safety of bisphosphonate therapy, long-term persistence and
      adherence to these agents remains low. This has serious consequences for patients
      with osteoporosis in that medication non-compliance is associated with
      significantly higher fracture risk. This review explores the unique
      physicochemical properties of bisphosphonates that allow more convenient
      intermittent dosing and whether less frequent dosing regimens improve compliance.
      Bisphosphonates are now available as oral drugs (taken daily, weekly, or monthly)
      or as intravenous preparations (given every 3 months or annually). The safety and
      efficacy of these various preparations are reviewed and compared, with particular
      emphasis on the newest agent to be approved, once-monthly risedronate. In
      contrast to monthly oral ibandronate, risedronate is the first and only monthly
      oral bisphosphonate to offer both vertebral and non-vertebral fracture reduction,
      based upon non-inferiority trials. Whether the greater convenience of this
      monthly oral bisphosphonate will translate into improved compliance and lower
      fracture risk is yet to be determined.

PMID- 21072271
TI  - Long-term safety and efficacy of raloxifene in the prevention and treatment of
      postmenopausal osteoporosis: an update.
AB  - The integrity of bone tissue and its remodeling that occurs throughout life
      requires a coordinated activity of osteoblasts and osteoclasts. The decreased
      estrogen circulating level during postmenopausal transition, with a prevalence of
      osteoclastic activity over osteoblastic activity, represents the main cause of
      bone loss and osteoporosis. Osteoporosis is a chronic disease requiring long-term
      therapy and it is important to evaluate the efficacy and safety of treatments
      over several years, as the fear of health risks is a common reason for
      discontinuing therapy. Raloxifene is a selective estrogen receptor modulator
      (SERM) leading to estrogen-agonist effects in some tissues and estrogen
      antagonist effects in others. Raloxifene is effective to prevent and treat
      postmenopausal vertebral osteoporosis, with reduction of spine fractures and, in
      post-hoc analyses, non-spine fractures in high-risk subjects. Moreover,
      raloxifene reduces the risk of invasive breast cancer and improves the levels of
      serum lipoprotein but with an increased risk of venous thromboembolism and fatal
      stroke, without significant change in the incidence of coronary events. For these
      reasons the overall risk-benefit profile is favorable. Therefore, when
      considering the use of raloxifene in a postmenopausal woman, we should take into
      account the osteoporosis-related individual risk and weigh the potential
      benefits, skeletal and extra-skeletal, against the health risks.

PMID- 21072272
TI  - Functional health literacy in Spanish-speaking Latinas seeking breast cancer
      screening through the National Breast and Cervical Cancer Screening Program.
AB  - BACKGROUND: This analysis examines the association between functional health
      literacy and follow-up after mammography among women receiving breast cancer
      screening at a National Breast and Cervical Cancer Early Detection Program site
      in New York City that provides universal bilingual case management. METHODS: A
      total of 707 Latinas who spoke Spanish as their primary language completed a
      survey of health and demographic characteristics and the Test of Functional
      Health Literacy in Spanish (TOFHLA-S). Survey results were matched with clinical
      outcome data. RESULTS: Among the survey participants, 98% were foreign-born and
      99% had no health insurance. While the study found significant differences in
      access to health information and past screening behavior, women without adequate
      health literacy in Spanish were no less likely to receive clinical resolution of
      abnormal mammograms within 60 days (81.8% overall; n = 110) or to return for a
      repeat mammogram within 18 months (57.2% overall; n = 697). In fact, among those
      referred for a Pap test (n = 310), women without adequate health literacy were
      more likely to receive a Pap test within 60 days of their mammogram than those
      with adequate health literacy (82% compared to 71%, OR: 1.83, 95% CI: 1.04-3.22).
      DISCUSSION: The lack of significantly lower follow-up outcomes among women with
      inadequate and marginal functional health literacy in this population of primary
      Spanish-speaking Latinas suggests that, once women have accessed screening
      services, programmatic approaches may exist to mitigate barriers to follow-up and
      to ensure optimal cancer screening outcomes for women of all literacy levels.

PMID- 21072273
TI  - Progress in analgesia for labor: focus on neuraxial blocks.
AB  - Neuraxial analgesia is widely accepted as the most effective and the least
      depressant method of providing pain relief in labor. Over the last several
      decades neuraxial labor analgesia techniques and medications have progressed to
      the point now where they provide high quality pain relief with minimal side
      effects to both the mother and the fetus while maximizing the maternal autonomy
      possible for the parturient receiving neuraxial analgesia. The introduction of
      the combined spinal epidural technique for labor has allowed for the rapid onset
      of analgesia with minimal motor blockade, therefore allowing the comfortable
      parturient to ambulate. Patient-controlled epidural analgesia techniques have
      evolved to allow for more flexible analgesia that is tailored to the individual
      needs of the parturient and effective throughout the different phases of labor.
      Computer integrated systems have been studied to provide seamless analgesia from
      induction of neuraxial block to delivery. New adjuvant drugs that improve the
      effectiveness of neuraxial labor analgesia while decreasing the side effects that
      may occur due to high dose of a single drug are likely to be added to future
      labor analgesia practice. Bupivacaine still remains a popular choice of local
      anesthetic for labor analgesia. New local anesthetics with less cardiotoxicity
      have been introduced, but their cost effectiveness in the current labor analgesia
      practice has been questioned.

PMID- 21072275
TI  - Tinidazole in the treatment of bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is the commonest cause of vaginal discharge in women of
      childbearing age. Oral metronidazole has long been established as an effective
      therapy in the treatment of BV. However, adverse effects due to metronidazole are
      frequent and this may lead to problems with adherence to a 7-day course of
      treatment and subsequently result in treatment failure. Oral tinidazole has been
      used to treat bacterial vaginosis for over 25 years but in a number of different
      dosage regimens. Placebo controlled trials have consistently shown increases in
      cure rate with tinidazole. Longer courses of treatment (eg, 1 g daily for 5 days)
      appear to be more effective than a 2 g oral single dose. Comparative studies
      suggest that oral tinidazole is equivalent to oral metronidazole, intravaginal
      clindamycin cream, and intravaginal metronidazole tablets, in efficacy in
      treating BV. However, tinidazole has a more favorable side effect profile than
      oral metronidazole notably with better gastrointestinal tolerability and less
      metallic taste. Bacterial vaginosis is associated with high rates of recurrence
      and appropriate management of such recurrences can prove difficult. Recurrent BV
      has been linked with persistence of Gardnerella vaginalis after treatment;
      however the clinical implications of the possible greater activity of tinidazole
      against G. vaginalis are not yet clear. Repeated courses of oral metronidazole
      may be poorly tolerated and an alternative but equally effective treatment that
      is better tolerated may be preferable. In comparison to oral metronidazole, cost
      is clearly an issue as oral metronidazole is considerably cheaper and available
      in generic form. However where avoidance of oral metronidazole is necessary
      because of side effects, oral tinidazole is a cost-effective alternative.

PMID- 21072274
TI  - Safety, efficacy and patient acceptability of the contraceptive and non
      contraceptive uses of the LNG-IUS.
AB  - Intrauterine devices (IUDs) provide highly effective, long-term, safe, reversible
      contraception, and are the most widely used reversible contraceptive method
      worldwide. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a T
      shaped IUD with a steroid reservoir containing 52 mg of levonorgestrel that is
      released at an initial rate of 20 MUg daily. It is highly effective, with a
      typical-use first year pregnancy rate of 0.1% - similar to surgical tubal
      occlusion. It is approved for 5 years of contraceptive use, and there is evidence
      that it can be effective for up to 7 years of continuous use. After removal,
      there is rapid return to fertility, with 1-year life-table pregnancy rates of 89
      per 100 for women less than 30 years of age. Most users experience a dramatic
      reduction in menstrual bleeding, and about 15% to 20% of women become amenorrheic
      1 year after insertion. The device's strong local effects on the endometrium
      benefit women with various benign gynecological conditions such as menorrhagia,
      dysmenorrhea, leiomyomata, adenomyosis, and endometriosis. There is also evidence
      to support its role in endometrial protection during postmenopausal estrogen
      replacement therapy, and in the treatment of endometrial hyperplasia.

PMID- 21072276
TI  - Aromatase inhibitor strategies in metastatic breast cancer.
AB  - Despite ongoing therapeutic innovations, metastatic breast cancer (MBC) remains a
      treatable but incurable disease. In the developed world, a diagnosis of MBC
      without a preceding diagnosis of early stage disease is a rare event. However,
      approximately one-third of women with early stage breast cancer ultimately
      experience a distant recurrence. Because the majority of breast cancers express
      estrogen and/or progesterone receptors and are accordingly considered hormone
      sensitive, therapeutic strategies that interfere with hormone-mediated
      tumorigenesis have been a cornerstone of the breast cancer management paradigm
      for decades. Historically, the selective estrogen receptor modulator tamoxifen
      has been the most extensively studied and widely used hormone maneuver in breast
      cancer. However, a recent therapeutic innovation, namely the successful
      development of third-generation aromatase inhibitors (AIs), has had a dramatic
      impact on the treatment paradigm for women with hormone-sensitive MBC. Because of
      the demonstrated efficacy in postmenopausal breast cancer patients, the generally
      favorable side-effect profile, and the convenience of oral administration, AIs
      are now in widespread clinical use. Currently, there are three clinically
      available third-generation AIs: two reversible, nonsteroidal AIs, letrozole and
      anastrozole; and one irreversible, steroidal AI, exemestane. All three agents are
      at least as efficacious as tamoxifen as monotherapy for postmenopausal women with
      hormone-sensitive MBC. Current clinical research aims to improve upon existing
      strategies by evaluating AIs in combination with systemic chemotherapy regimens
      and/or novel targeted agents. It is hoped that these therapeutic innovations will
      lead to ongoing improvements in quality of life parameters and ideally survival
      for women with hormone-sensitive MBC.

PMID- 21072277
TI  - The role of progesterone in prevention of preterm birth.
AB  - Preterm birth continues to provide an enormous challenge in the delivery of
      perinatal health care, and is associated with considerable short and long-term
      health consequences for surviving infants. Progesterone has a role in maintaining
      pregnancy, by suppression of the calcium-calmodulin-myosin light chain kinase
      system. Additionally, progesterone has recognized anti-inflammatory properties,
      raising a possible link between inflammatory processes, alterations in
      progesterone receptor expression and the onset of preterm labor. Systematic
      reviews of randomized controlled trials evaluating the use of intramuscular and
      vaginal progesterone in women considered to be at increased risk of preterm birth
      have been published, with primary outcomes of perinatal death, preterm birth <34
      weeks, and neurodevelopmental handicap in childhood. Eleven randomized controlled
      trials were included in the systematic review, involving 2714 women and 3452
      infants, with results presented according to the reason women were considered to
      be at increased risk of preterm birth. While there is a potential beneficial
      effect in the use of progesterone for some women considered to be at increased
      risk of preterm birth, primarily in the reduction in the risk of preterm birth
      before 34 weeks gestation, it remains unclear if the observed prolongation of
      pregnancy translates into improved health outcomes for the infant.

PMID- 21072278
TI  - Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl
      estradiol contraceptive pills in the treatment of premenstrual dysphoric
      disorder.
AB  - Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%-8% of
      reproductive age women. Multiple therapeutic modalities have been evaluated with
      varying efficacy for the associated somatic and mood symptoms. The majority of
      older studies had shown that oral contraceptive pills (OCs) were most effective
      for the physical symptoms. However, newer OCs containing a novel progestin,
      drospirenone, have shown promise in alleviating both the somatic and
      affective/behavioral symptoms. This progestin, which is a derivative of
      spironolactone, has both antimineralocorticoid and antiandrogenic activity. A
      24/4 formulation containing 20 MUg of ethinyl estradiol has been found effective
      in randomized double-blind placebo-controlled trials utilizing established scales
      documenting symptoms associated with PMDD. Multiple studies have shown that
      drospirenone-containing OCs are safe without evidence of clinically adverse
      effects on carbohydrate metabolism, lipids, blood pressure, weight, serum
      potassium or increased thrombotic events compared to other low dose OCs. In
      addition, significant improvements have been demonstrated in acne, hirsutism, and
      fluid retention symptoms. Several open label studies demonstrated good patient
      compliance and reported satisfaction with the method. Because of the significant
      placebo effect demonstrated in the blinded placebo-controlled trials, additional
      large randomized placebo-controlled trials are needed to confirm the efficacy of
      the drospirenone OCs in the treatment of PMDD. However, this OC formulation
      appears to be a promising therapeutic modality.

PMID- 21072279
TI  - Treating postmenopausal osteoporosis in women at increased risk of fracture -
      critical appraisal of bazedoxifene: a review.
AB  - Several categories of drugs to treat osteoporosis exist in the form of
      bisphosphonates, strontium, parathyroid hormone, and selective estrogen receptor
      modulators (SERM). Advantages and disadvantages exist for each category as some
      patients may, for example, not tolerate bisphosphonates for gastrointestinal side
      effects, and especially in women in whom osteoporosis is frequent, several
      options for treatment are needed. The objectives of this review were to
      critically appraise the effects of bazedoxifene on risk of fractures especially
      in women at high risk of fractures. A systematic literature search was conducted
      for studies, especially randomized controlled trials with fractures as end
      points. Bazedoxifene is a new member of the SERM group. The literature search
      identified one randomized controlled trial with fractures as end-point. This was
      a 3-year randomized double-blind placebo controlled trial in which 7492
      postmenopausal women aged 55 to 85 years were randomly allocated to 1)
      bazedoxifene (20 [n = 1886] or 40 [n = 1872] mg/day); 2) raloxifene (60 mg/day, n
      = 1849); or 3) placebo (n = 1885). The risk of vertebral fractures decreased with
      both 20 (HR 0.58, 95% CI 0.38 to 0.89) and 40 (HR 0.63, 95% CI 0.42 to 0.96) mg
      of bazedoxifene per day compared to placebo. There was no reduction in non
      vertebral fractures. A subgroup of women with a priori high risk of fractures was
      identified post hoc. In this subgroup there was a reduction in the risk of non
      vertebral fractures with the 20 mg dose of bazedoxifene compared to placebo (HR
      0.50, 95% CI 0.28 to 0.90). In the 40 mg bazedoxifene group no significant
      reduction in non-vertebral fractures was seen in this subgroup (HR 0.70, 95% CI
      0.40 to 1.20). In general post-hoc defined subgroup analyses should be
      interpreted with caution. However, the results indicate that bazedoxifene may be
      effective in preventing vertebral fractures in postmenopausal women with
      osteoporosis.

PMID- 21072280
TI  - Treating dyspareunia caused by vaginal atrophy: a review of treatment options
      using vaginal estrogen therapy.
AB  - Vulvovaginal atrophy (VVA) and dryness are common symptoms of the decline in
      endogenous production of estrogen at menopause and often result in dyspareunia.
      Yet while 10% to 40% of women experience discomfort due to VVA, it is estimated
      that only 25% seek medical help. The main goals of treatment for vaginal atrophy
      are to improve symptoms and to restore vaginal and vulvar anatomic changes.
      Treatment choices for postmenopausal dyspareunia resulting from vulvovaginal
      atrophy will depend on the underlying etiology and might include individualized
      treatment. A number of forms of vaginal estrogen and manner of delivery are
      currently available to treat moderate to severe dyspareunia caused by VVA. They
      all have been shown to be effective and are often the preferred treatment due to
      the targeted efficacy for urogenital tissues while resulting in only minimal
      systemic absorption. Both healthcare professionals and patients often find it
      difficult to broach the subject of sexual problems associated with VVA. However,
      with minimal effort to initiate a conversation about these problems, healthcare
      providers can provide useful information to their postmenopausal patients in
      order to help them each choose the optimal treatment for their needs and
      symptoms.

PMID- 21072281
TI  - Assessment of musculoskeletal system in women with jumping mechanography.
AB  - The purpose of this study was to investigate and add reference data about the
      musculoskeletal system in women. The mechanography system of the LeonardoTM
      platform (Novotec, Germany) was used to measure parameters of movement (velocity,
      force, power) in 176 healthy Greek women aged 20-79 years, separated according to
      age decade in six groups: group 1 (n = 12), 20-29 years; group 2 (n = 14), 30-39
      years; group 3 (n = 33), 40-49 years; group 4 (n = 59), 50-59 years including 21
      postmenopausal; group 5 (n = 31), 60-69 years including 12 postmenopausal; and
      group 6 (n = 27), 70-79 years all postmenopausal. This system measures forces
      applied to the plate over time, calculates through acceleration the vertical
      velocity of center of gravity and using force and velocity it calculates power of
      vertical movements. All women performed a counter-movement jump (brief squat
      before the jump) with freely moving arms. Weight was recorded on the platform
      before the jump and height was measured with a wall-mounted ruler. Body weight
      and body mass index were gradually increased; on the contrary height and all
      movement parameters except force (velocity, power) were statistically decreased
      during aging and after menopause.

PMID- 21072282
TI  - Prevention of cervical, vaginal, and vulval cancers: role of the quadrivalent
      human papillomavirus (6, 11, 16, 18) recombinant vaccine.
AB  - The relationship between the human papillomavirus (HPV) and malignancies of the
      uterine cervix, vagina, and vulva has been established. The development of a
      quadrivalent HPV recombinant prophylactic vaccine represents the first time in
      history that primary prevention of these cancers is offered to girls and women.
      The prevalence of oncogenic HPV subtypes in cervical cancers has been the most
      studied, but prevalence has also been established for vaginal and vulvar cancers.
      Clinical trials demonstrate impressive efficacy in disease prevention as well as
      excellent safety and tolerability. The role the quadrivalent HPV recombinant
      vaccine promises to have in the reduction of gynecologic malignancies will depend
      on various factors, including acceptance and accessibility of the vaccine,
      duration of immunity, and cross-protection against other oncogenic HPV subtypes.
      The HPV vaccine's role in disease reduction will probably be viewed in the
      context of a strategy that involves continued secondary screening and lifestyle
      modification to reduce modifiable risk factors, along with widespread
      vaccination.

PMID- 21072283
TI  - Mandatory fortification with folic acid in the United States appears to have
      adverse effects on histone methylation in women with pre-cancer but not in women
      free of pre-cancer.
AB  - OBJECTIVE: To evaluate whether mandatory fortification of grain products with
      folic acid in the US is associated with changes in histone methylation in cells
      involved in cervical carcinogenesis. METHODS: Cervical specimens obtained before
      (1990 to 1992) and after mandatory folic acid fortification (2000 to 2002) were
      used to examine the degree of histone methylation (H3 Lys-9) by
      immunohistochemistry. 91 women (51 before and 40 after fortification) were
      diagnosed with cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in
      situ (CIS) and sections utilized in the study also contained normal, reactive or
      metaplastic cervical epithelium, CIN 1 or CIN 2. 64 women (34 before and 30 after
      fortification) were free of CIN and these sections contained only normal or
      reactive cervical epithelium. Immunohistochemical staining for H3 Lys-9, its
      assessment in different cell or lesion types and data entry were blinded for
      fortification status. For each cell type or lesion category we used PROC MIXED in
      SAS with the specimen identifier as a random effect and the robust variance
      estimator to estimate age- and race-adjusted intensity score for H3 Lys-9 in the
      pre- and post-fortification periods. RESULTS: Degree of H3 Lys-9 methylation was
      significantly higher (P < 0.0001) in >=CIN 2 lesions (CIN 2, CIN 3 and CIS) than
      in <=CIN 1 lesions (CIN 1, normal, reactive and metaplastic), in both pre- and
      post-fortification CIN 3/CIS specimens. Age- and race-adjusted mean H3 Lys-9
      score was significantly higher in all cell or lesion types in CIN 3/CIS specimens
      obtained in the post-fortification period compared to pre-fortification period (P
      < 0.05, all comparisons). In contrast, in specimens obtained from women free of
      CIN, Lys-9 methylation in normal/reactive cervical epithelium was significantly
      lower in post-fortification specimens than in pre-fortification specimens (P =
      0.03). CONCLUSIONS: Higher levels of Lys-9 methylation in >=CIN 2 compared to
      <=CIN 1 lesions suggest that higher Lys-9 methylation is associated with
      progression of lower grade CIN to higher grade CIN. Higher Lys-9 methylation in
      cervical tissues of women diagnosed with CIN 3 in the post-fortification period
      than in pre-fortification period suggest that fortification may adversely affect
      histone methylation in already initiated cells. Lower Lys-9 methylation in
      normal/reactive cervical cells of women free of CIN in the post-fortification
      period than pre-fortification on the other hand suggests that fortification is
      likely to protect against initiation of carcinogenic process in the cervix. These
      results suggest that mandatory fortification with folic acid in the US seems to
      have different effects on cancer depending on the stage of carcinogenesis.
      Because this is the first study to report folic acid fortification-associated
      differences in histone methylation and because of the limitations inherent to the
      approach we have taken to demonstrate these differences, validation of the
      results in other study populations or with other techniques for assessing histone
      methylation is necessary.

PMID- 21072284
TI  - Advances in labor analgesia.
AB  - The pain of childbirth is arguably the most severe pain most women will endure in
      their lifetimes. The pain of the early first stage of labor arises from dilation
      of the lower uterine segment and cervix. Pain from the late first stage and
      second stage of labor arises from descent of the fetus in the birth canal,
      resulting in distension and tearing of tissues in the vagina and perineum. An
      array of regional nerve blocks, systemic analgesic, and nonpharmacologic
      techniques are currently used for labor analgesia. Nonpharmacologic methods are
      commonly used, but the effectiveness of these techniques generally lacks rigorous
      scientific study. Continuous labor support has been shown to decrease the use of
      pharmacologic analgesia and shorten labor. Intradermal water injections decrease
      back labor pain. Neuraxial labor analgesia (most commonly epidural or combined
      spinal-epidural) is the most effective method of pain relief during childbirth,
      and the only method that provides complete analgesia without maternal or fetal
      sedation. Current techniques commonly combine a low dose of local anesthetic
      (bupivacaine or ropivacaine) with a lipid soluble opioid (fentanyl or
      sufentanil). Neuraxial analgesia does not increase the rate of cesarean delivery
      compared to systemic opioid analgesia; however, dense neuraxial analgesia may
      increase the risk of instrumental vaginal delivery.

PMID- 21072286
TI  - Current status of maintenance therapy for advanced ovarian cancer.
AB  - Even after countered with and responding to maximal surgical and chemotherapy
      efforts, advanced ovarian cancer usually ultimately recurs. One strategy employed
      to forestall recurrence is maintenance chemotherapy, an extension of treatment
      following a complete response to conventional measures. Many agents have been
      studied and many more are currently under investigation in maintenance regimens.
      While phase III data suggest that taxane maintenance prolongs progression-free
      survival, no overall survival benefit has been established. This article reviews
      the current status of maintenance therapy for advanced ovarian cancer, including
      phase III evidence and new and upcoming trials.

PMID- 21072285
TI  - Targeting HER2 in breast cancer: overview of long-term experience.
AB  - The ability to probe diseases at the genomic level has improved our understanding
      and enhanced the treatment of breast cancer. One important finding relates to the
      HER2 oncogene which encodes a novel transmembrane receptor that, when
      overexpressed, appears to confer growth and survival advantages to breast tumor
      cells. This fortuitous discovery enabled researchers to develop agents which
      could inhibit receptor-mediated tumor cell signaling. Numerous clinical trials of
      such agents have demonstrated improved outcomes in patients with HER2-positive
      breast cancer. Nonetheless, not all tumors respond to therapy targeting the
      receptor, while relapses occur after an initial response to treatment. This paper
      provides a historical and current perspective of the treatment of patients with
      HER2-positive breast cancer.

PMID- 21072288
TI  - Update on the efficacy, safety, and adherence to treatment of full length
      parathyroid hormone, PTH (1-84), in the treatment of postmenopausal osteoporosis.
AB  - Full length (1-84) parathyroid hormone (PTH) was introduced in Europe as a
      treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84) in
      the prevention of vertebral fractures is very high, and is similar to that of
      teriparatide. Its action in the prevention of femoral fractures has yet to be
      fully demonstrated, but the incidence of such fractures in trials was very low,
      and a decrease in nonvertebral fractures was seen in high-risk patients. The
      effect on bone mineral density (BMD) was clearly demonstrated in the spine and
      also in the hip. The effects on BMD were evident and increased progressively with
      treatment until 36 months. After its discontinuation there was a clear decrease
      in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric
      density and bone volume in trabecular sites were also reported. Moreover, a bone
      volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria
      are frequent consequences of PTH treatment, but rarely have clinical effects and
      are usually well controlled by reducing calcium and vitamin D supplementation.

PMID- 21072287
TI  - Raising HDL cholesterol in women.
AB  - High-density lipoprotein cholesterol (HDL-C) concentration is essential in the
      determination of coronary heart disease (CHD) risk in women. This is especially
      true in the postmenopausal state, where lipid profiles and CHD risk mimic that of
      age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C
      levels may have particular significance during the transition to menopause. This
      review discusses HDL-C-raising therapies and the role of HDL in the primary
      prevention of CHD in women. Lifestyle-based interventions such as dietary change,
      aerobic exercise regimens, and smoking cessation are initial steps that are
      effective in raising HDL-C, and available data suggest women respond similarly to
      men with these interventions. When combined with pharmacotherapy, the effects of
      these lifestyle alterations are further amplified. Though studies demonstrating
      gender-specific differences in therapy are limited, niacin continues to be the
      most effective agent in raising HDL-C levels, especially when used in combination
      with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy
      show much promise in further raising HDL-C levels and improving cardiovascular
      outcomes.

PMID- 21072290
TI  - Efficacy and safety of combined ethinyl estradiol/drospirenone oral
      contraceptives in the treatment of acne.
AB  - Acne is a common disorder affecting the majority of adolescents and often extends
      into adulthood. The central pathophysiological feature of acne is increased
      androgenic stimulation and/or end-organ sensitivity of pilosebaceous units
      leading to sebum hypersecretion and infundibular hyperkeratinization. These
      events lead to Propionibacterium acnes proliferation and subsequent inflammation.
      Hormonal therapy, including combined oral contraceptives (OCs), can attenuate the
      proximate androgenic trigger of this sequence. For many women, hormonal therapy
      is a rational option for acne treatment as it may be useful across the spectrum
      of severity. Drospirenone (DRSP) is a unique progestin structurally related to
      spironolactone with progestogenic, antimineralocorticoid, and antiandrogenic
      properties. It is available in 2 combined OC preparations (30 MUg EE/3 mg DRSP;
      Yasmin((r)) in a 21/7 regimen; and 20 MUg EE/3 mg DRSP; Yaz((r)) in a 24/4
      regimen). These preparations are bereft of the fluid retentional side effects
      typical of other progestins and their safety has been demonstrated in large
      epidemiological studies in which no increased risk of vascular thromboembolic
      disease or arrhythmias was observed. In acne, the efficacy of DRSP-containing OCs
      has been shown in placebo-controlled superiority trials and in active-comparator
      non-inferiority trials.

PMID- 21072289
TI  - Review of the safety, efficacy, costs and patient acceptability of recombinant
      follicle-stimulating hormone for injection in assisting ovulation induction in
      infertile women.
AB  - Anovulation is a common cause of female subfertility. Treatment of anovulation is
      aimed at induction of ovulation. In women with clomiphene-citrate resistant WHO
      group II anovulation, one of the treatment options is ovulation induction with
      exogenous follicle-stimulating hormone (FSH or follitropin). FSH is derived from
      urine or is produced as recombinant FSH. Two forms of recombinant FSH are
      available - follitropin alpha and follitropin beta. To evaluate the efficacy,
      safety, costs and acceptability of recombinant FSH, we performed a review to
      compare recombinant FSH with urinary-derived FSH products. Follitropin alpha,
      beta and urinary FSH products appeared to be equally effective in terms of
      pregnancy rates. Patient safety was also found to be comparable, as the incidence
      of side effects including multiple pregnancies was similar for all FSH products.
      In practice follitropin alpha and beta may be more convenient to use due to the
      ease of self-administration, but they are also more expensive than the urinary
      products.

PMID- 21072291
TI  - Strontium ranelate in postmenopausal osteoporosis treatment: a critical
      appraisal.
AB  - Osteoporosis is a progressive and debilitating disease characterized by a massive
      bone loss with a deterioration of bone tissues, and a propensity for a fragility
      fracture. Strontium ranelate is the first antiosteoporotic treatment that has
      dual mode of action and simultaneously increases bone formation, while decreasing
      bone resorption, thus rebalancing bone turnover formation. Strontium ranelate
      rebalances bone turnover in favor of improved bone geometry, cortical thickness,
      trabecular bone morphology and intrinsic bone tissue quality, which translates
      into enhanced bone strength. This review describes the mechanism of the strontium
      ranelate action and its effects on bone mineral density, bone turnover, and
      osteoporotic fractures. The efficacy of strontium ranelate in postmenopausal
      osteoporosis treatment to reduce the risk of vertebral and hip fractures has been
      highlighted in several randomized, controlled trials. Treatment efficacy with
      strontium ranelate has been documented across a wide range of patient profiles:
      age, number of prevalent vertebral fractures, body mass index, and a family
      history of osteoporosis. Because strontium ranelate has a large spectrum of
      efficacy, it can be used to treat different subgroups of patients with
      postmenopausal osteoporosis. Strontium ranelate was shown to be relatively well
      tolerated and the safety aspects were good. Strontium ranelate should be
      considered as a first-line treatment for postmenopausal osteoporotic patients.

PMID- 21072292
TI  - Indian women with higher serum concentrations of folate and vitamin B12 are
      significantly less likely to be infected with carcinogenic or high-risk (HR)
      types of human papillomaviruses (HPVs).
AB  - BACKGROUND: Studies conducted in the USA have demonstrated that micronutrients
      such as folate and vitamin B12 play a significant role in modifying the natural
      history of high-risk human papillomaviruses (HR-HPVs), the causative agent for
      developing invasive cervical cancer (CC) and its precursor lesions. OBJECTIVE:
      The purpose of the current study was to investigate whether these micronutrients
      have similar effects on HR-HPV infections in Indian women. METHODS: The
      associations between serum concentrations of folate and vitamin B12 and HR-HPV
      infections were evaluated in 724 women who participated in a CC screening study
      in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12
      concentrations were measured by using a competitive radio-binding assay. Digene
      hybrid capture 2 (HC2) assay results were used to categorize women into two
      groups, positive or negative for HR-HPVs. Unconditional logistic regression
      models specified a binary indicator of HC2 (positive/negative) as the dependent
      variable and serum folate concentrations combined with serum vitamin B12
      concentrations as the independent predictor of primary interest. Models were
      fitted, adjusting for age, education, marital status, parity, type of fuel used
      for cooking and smoking status. RESULTS: Women with higher concentrations of
      serum folate (>6 ng/mL) and vitamin B12 (>356 pg/mL) were at lower risk of being
      positive for HR-HPVs compared to those with serum folate <=6 ng/mL and serum
      vitamin B12 <= 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08-0.89;
      P = 0.03). CONCLUSIONS: These results demonstrated that improving folate and
      vitamin B12 status in Indian women may have a beneficial impact on the prevention
      of CC. Micronutrient based interventions for control of HR-HPV infections may
      represent feasible alternatives to vaccine based approaches to HPV disease
      prevention, which are currently unaffordable for use in resource limited areas in
      rural India.

PMID- 21072293
TI  - Intergenerational associations between a consensual childhood sexual experience
      and adult substance abuse among Latina mothers and daughters.
AB  - PURPOSE: Early onset of sexual activity has been linked to later substance abuse.
      Our study aimed to further describe the associations between Latina mothers' and
      daughters' early sexual activity and adult substance abuse. METHODS: A survey was
      conducted with 92 Latina mother-daughter dyads whose members never experienced
      sexual abuse. Childhood sexual experience was defined as the occurrence of a
      consensual sexual encounter at the age of 15 years or younger. Substance abusers
      were identified by the extent of substance use during the 12 months prior to the
      interview. Path analysis was used to fit our conceptual models to the data. MAIN
      FINDINGS: Daughters' current, adult substance abuse was associated independently
      with: their own childhood sexual experience (odds ratio [OR] = 6.0) and mothers'
      current, adult substance abuse (OR = 2.0). Compared with daughters who first
      experienced sex after the age of 19, the odds of using substances were 17.7 times
      higher among daughters who had childhood sexual experience and 3.8 times higher
      among daughters who first experienced sex between the age of 16-19 years.
      Explicitly, sexual experiences between the ages of 16-19 years were also risk
      factors for later adult substance abuse. Mothers' childhood sexual experience (OR
      = 7.3) was a strong predictor for daughters' childhood sexual experience.
      CONCLUSIONS: Our study supported a link between mother and daughter childhood
      sexual experience among Latinas, and indicated it is a correlate of adult
      substance abuse. Family based substance abuse prevention efforts and future
      longitudinal studies should consider maternal childhood sexual experience as a
      potential indication of risk for Latina daughters.

PMID- 21072294
TI  - Prevention of maternal cytomegalovirus infection: current status and future
      prospects.
AB  - Human cytomegalovirus (CMV) infection is the most common cause of perinatal viral
      infection in the developed world, resulting in approximately 40,000 congenitally
      infected infants in the United States each year. Congenital CMV infection can
      produce varying degrees of neurodevelopmental disabilities. The significant
      impact of congenital CMV has led the Institute of Medicine to rank development of
      a CMV vaccine as a top priority. Vaccine development has been ongoing; however no
      licensed CMV vaccine is currently available. Treatment of pregnant women with CMV
      hyperimmune globulin has shown promising results, but has not been studied in
      randomized controlled trials. Education on methods to prevent CMV transmission,
      particularly among young women of child-bearing age, should continue until a CMV
      vaccine becomes available. The epidemiology, clinical manifestations, prevention
      strategies, and treatment of CMV infections are reviewed.

PMID- 21072295
TI  - Profile of teriparatide in the management of postmenopausal osteoporosis.
AB  - One out of every 2 women within postmenopause are at risk of fracture due to
      osteoporosis. Fortunately, a growing arsenal of therapies is becoming available
      to treat this disease and prevent fracture. A new class of anabolic agents has
      emerged within the last decade that brought with it a new concept in osteoporosis
      therapy: building new stronger bone rather than simply inhibiting bone turnover.
      Evidence is accumulating to understand how to best utilize these new agents, and
      which patients benefit most. This article will review the effectiveness, risks,
      timing and clinical uses of teriparatide in postmenopausal osteoporosis.

PMID- 21072296
TI  - Gender-related mortality for HIV-infected patients on highly active
      antiretroviral therapy (HAART) in rural Uganda.
AB  - The purpose of this study was to examine gender differences in mortality for
      human immunodeficiency virus (HIV) patients in rural Western Uganda after six
      months of highly active antiretroviral therapy (HAART). Three hundred eighty five
      patients were followed up for six months after initiating HAART. Statistical
      analysis included descriptive, univariate and multivariate methods, using Kaplan
      Meier estimates of survival distribution and Cox proportional hazards regression.
      Mortality in female patients (9.0%) was lower than mortality in males (13.5%),
      with the difference being almost statistically significant (adjusted hazard ratio
      for females 0.55; 95% confidence interval [CI]: 0.28-1.07; P = 0.08). At
      baseline, female patients had a significantly higher CD4+ cell count than male
      patients (median 147 cells/MUL vs 120 cells/MUL; P < 0.01). A higher CD4+ cell
      count and primary level education were strongly associated with better survival.
      The higher CD4+ cell count in females may indicate that they accessed HAART
      services at an earlier stage of their disease progression than males. A
      borderline statistically significant lower mortality rate in females shows that
      females fare better on treatment in this context than males. The association
      between lower mortality and higher CD4+ levels suggest that males are not
      accessing treatment early enough and that more concerted efforts need to be made
      by HAART programs to reach male HIV patients.

PMID- 21072297
TI  - Emergency contraception: potential role of ulipristal acetate.
AB  - Unintended pregnancy is a global reproductive health problem. Emergency
      contraception (EC) provides women with a safe means of preventing unwanted
      pregnancies after having unprotected intercourse. While 1.5 mg of levonorgestrel
      (LNG) as a single dose or in 2 doses with 12 hours apart is the currently gold
      standard EC regimen, a single dose of 30 mg ulipristal acetate (UPA) has recently
      been proposed for EC use up to 120 hours of unprotected intercourse with similar
      side effect profiles as LNG. The main mechanism of action of both LNG and UPA for
      EC is delaying or inhibiting ovulation. However, the 'window of effect' for LNG
      EC seems to be rather narrow, beginning after selection of the dominant
      follicular and ending when luteinizing hormone peak begins to rise, whereas UPA
      appears to have a direct inhibitory effect on follicular rupture which allows it
      to be also effective even when administered shortly before ovulation, a time
      period when use of LNG is no longer effective. These experimental findings are in
      line with results from a series of clinical trials conducted recently which
      demonstrate that UPA seems to have higher EC efficacy compared to LNG. This
      review summarizes some of the data available on UPA used after unprotected
      intercourse with the purpose to provide evidence that UPA, a new type of second
      generation progesterone receptor modulator, represents a new evolutionary step in
      EC treatment.

PMID- 21072298
TI  - Non-contraceptive applications of the levonorgestrel intrauterine system.
AB  - Intrauterine progestins have many important current and potential gynecologic
      applications. This article describes the evidence for use of intrauterine
      progestin for common gynecologic conditions beyond its important role in
      contraception. The pharmacology of and selection criteria for use of the
      levonorgestrel intrauterine device is discussed, and the evidence for use of
      intrauterine progestin delivery for menorrhagia, endometriosis management,
      uterine fibroids, adenomyosis and endometrial hyperplasia is reviewed.

PMID- 21072299
TI  - Examining the use of oral contraceptives in the management of acne.
AB  - Combined oral contraceptive pills (cOCPs) are often used in the treatment of acne
      in females. They are effective, safe, and easy to use in appropriate patients in
      combination with more conventional acne therapies. This article will briefly
      address the physiologic rationale for the use of cOCPs in the treatment of acne.
      It will also review efficacy by examining relevant clinical trials. Safety
      considerations and the adverse event profile for oral contraceptives will be
      presented. Finally, practical considerations for prescribing cOCPs will be
      discussed.

PMID- 21072300
TI  - Breast cancer burden in central Sudan.
AB  - Breast cancer is a worldwide disease resulting in many deaths. Although breast
      cancer incidence is lower in Sub-Saharan African countries than in developed
      countries, African women are more likely than women in the developed world to be
      diagnosed at later stages of the disease and, thus, are more likely to die from
      it. This is due to the lack of awareness by women, accessibility to screening
      methods, and availability of African-based research findings that would influence
      decision making at the governmental level. This descriptive study was undertaken
      to shed light on the type, stage and age distribution of breast cancer at
      diagnosis in women living in central Sudan encompassing al-Gezira, Blue Nile,
      White Nile, and Sennar States. Cases comprised 1255 women from central Sudan
      diagnosed with breast cancer and referred to and treated at Institute of Nuclear
      Medicine, Molecular Biology, and Oncology, from January 1999 to December 2006.
      Data revealed that 74% of the women were <50 years old or premenopausal. Invasive
      ductal carcinoma was the most common pathology (82%) and women presenting with
      stage III or higher tumors that had already metastasized, while ductal carcinoma
      in situ was the least prevalent (0.5%) finding. Estrogen and progesterone
      receptors expression were performed on a limited number of samples and the
      overwhelming majority of cases were observed to be negative for estrogen and
      progesterone receptors expression.

PMID- 21072301
TI  - The triple test as a screening technique for Down syndrome: reliability and
      relevance.
AB  - The triple test is a second trimester screening test used to identify those
      pregnant women who should be offered a diagnostic test to identify whether their
      fetus has an aneuploidy. It was first described in 1988, but has largely been
      superseded by newer tests either conducted earlier in the first trimester (ie,
      the combined test, using ultrasound measurement of nuchal translucency, pregnancy
      associated plasma protein A, and human chorionic gonadotrophin [hCG]) or in the
      second trimester (ie, the quadruple test, using alpha-fetoprotein, hCG, uE3, and
      inhibin). These newer tests have been introduced because they offer greater
      detection and lower screen positive results thereby enhancing diagnosis rates,
      while decreasing the risk of iatrogenic harm caused by the invasive testing
      required when collecting suitable sample tissue. Noninvasive alternatives to the
      triple test have been identified, but these have not been adopted despite 13
      years of development. It is likely, therefore, that the triple test (or variants
      thereof) will continue to be used in routine antenatal care for the foreseeable
      future.

PMID- 21072302
TI  - Success of frozen embryo transfer: Does the type of gonadotropin influence the
      outcome?
AB  - OBJECTIVES: To determine whether there is a difference in outcome between
      different ovulation-induced cycles after frozen-thawed embryo transfer (FET).
      METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group's
      trials register in May 2009, the Cochrane Central Register of Controlled Trials
      (Cochrane Library, Issue 1, 2008), ISI Web of Knowledge (1985 to August 2009),
      and reference lists of articles. Relevant conference proceedings were hand
      searched and researchers in the field were contacted. Randomized controlled
      trials and retrospective studies were included, comparing the various cycle
      regimens and different methods during FET in assisted reproductive technology,
      ie, in vitro fertilization and intracytoplasmic sperm injection. RESULTS: Using
      the agonist long protocol for downregulation, five trials provided extractable
      data for live-birth rates, ongoing pregnancy, and clinical pregnancy rates
      following FET. One trial provided extractable data for clinical pregnancy rate.
      There was no evidence of a significant difference in any outcome between the
      users of urinary gonadotropins versus recombinant follicle-stimulating hormone.
      Data on implantation and miscarriage rates following FET were not available for
      analysis. CONCLUSIONS: It seems that clinical pregnancy rate after FET is not
      influenced by the type of gonadotropins used. Research should be directed towards
      improving freezing and thawing techniques.

PMID- 21072303
TI  - New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an
      evolutionary step in birth control.
AB  - AIM: To review milestones in development of oral contraceptive pills since their
      introduction in the US 50 years ago in order to better understand how a new
      formulation with low-dose estrogen in an extended-cycle pattern fits into the
      evolution of birth control pills. METHODS: This is a review of trends in the
      development of various birth controls pills and includes data from phase III
      clinical trials for this new formulation. RESULTS: The first birth control pill
      was a very high-dose monophasic formulation with the prodrug estrogen mestranol
      and a first-generation progestin. Over the decades, the doses of hormones have
      been markedly reduced, and a new estrogen and several different progestins were
      developed and used in different dosing patterns. The final element to undergo
      change was the 7-day pill-free interval. Many of these same changes have been
      made in the development of extended-cycle pill formulation. CONCLUSION: The
      newest extended-cycle oral contraceptive formulation with 84 active pills, each
      containing 20 MUg ethinyl estradiol and 100 MUg levonorgestrel, represents an
      important evolution in birth control that incorporates lower doses of estrogen
      (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled
      bleeding episodes (to meet women's desires for fewer and shorter menses) and the
      use of low-dose estrogen in place of placebo pills (to reduce the number of days
      of unscheduled spotting and bleeding). Hopefully, this unique formation will
      motivate women to be more successful contraceptors.

PMID- 21072304
TI  - Factors affecting receipt of chemotherapy in women with breast cancer.
AB  - AIMS: To review literature describing factors associated with receipt of
      chemotherapy for breast cancer, to better understand what factors are most
      relevant to women's health and whether health disparities are apparent, and to
      assess how these factors might affect observational studies and outcomes
      research. Patterns of care for metastatic breast cancer, for which no standard-of
      care exists, were of particular interest. METHODS: Relevant studies written in
      English, Italian, French, or Spanish, published in 2000 or later, were identified
      through MEDLINE and reviewed. Review articles and clinical trials were excluded;
      all observational studies and surveys were considered. Articles were reviewed for
      any discussion of patient characteristics, hospital/physician/insurance
      characteristics, psychosocial characteristics, and clinical characteristics
      affecting receipt of chemotherapy by breast cancer patients. RESULTS: In general,
      factors associated with increased likelihood of receiving chemotherapy included
      younger age, being Caucasian, having good general health and few co-morbidities,
      having more severe clinical disease, having responded well to previous treatment,
      and having breast cancer that is estrogen- or progesterone-receptor-negative.
      Many of the clinical factors found to increase the likelihood of receiving
      chemotherapy were consistent with current oncology guidelines. Of the relevant 19
      studies identified, only six (32%) reported data specific to metastatic cancer;
      most studies aggregated women with stage I-IV for purposes of analysis.
      CONCLUSION: Studies of patterns of care in breast cancer treatment can help
      identify challenges in health care provided to particular subgroups of women and
      can aid researchers in designing studies that account for such factors in
      clinical and outcomes research. Although scarce, studies evaluating only women
      with metastatic breast cancer indicate that factors affecting decisions related
      to receipt of chemotherapy are similar across stage for this disease.

PMID- 21072306
TI  - Management of preterm labor: atosiban or nifedipine?
AB  - Preterm birth is strongly associated with neonatal death and long-term
      neurological morbidity. The purpose of tocolytic drug administration is to
      postpone threatening preterm delivery for 48 hours to allow maximal effect of
      antenatal corticosteroids and maternal transportation to a center with
      specialized neonatal care facilities. There is uncertainty about the value of
      atosiban (oxytocin receptor antagonist) and nifedipine (calcium channel blocker)
      as first-line tocolytic drugs in the management of preterm labor. For nifedipine,
      concerns have been raised about unproven safety, lack of placebo-controlled
      trials, and its off-label use. The tocolytic efficacy of atosiban has also been
      questioned because of a lack of reduction in neonatal morbidity. This review
      discusses the available evidence, the pros and cons of either drug and aims to
      provide information to support a balanced choice of first-line tocolytic drug:
      atosiban or nifedipine?

PMID- 21072305
TI  - Management of menopause-associated vasomotor symptoms: Current treatment options,
      challenges and future directions.
AB  - Hot flashes are one of the most common and distressing symptoms associated with
      menopause, occurring in more than 75% of postmenopausal women. They are
      especially problematic in breast cancer patients since some breast cancer
      therapies can induce hot flashes. For mild hot flashes, it is proposed that
      behavioral modifications are the first step in management. Hormonal therapies,
      including estrogens and progestogens, are the most well known effective agents in
      relieving hot flashes; however, the safety of these agents is controversial.
      There is an increasing amount of literature on nonhormonal agents for the
      treatment of hot flashes. The most promising data regard newer antidepressant
      agents such as venlafaxine, which reduces hot flashes by about 60%. Gabapentin is
      another nonhormonal agent that is effective in reducing hot flashes. While many
      complimentary therapies, including phytoestrogens, black cohosh, and
      dehydroepiandrosterone, have been explored for the treatment of hot flashes; none
      can be recommended at this time. Furthermore, there is a lack of strong evidence
      to support exercise, yoga, or relaxation for the treatment of hot flashes. Paced
      respirations and hypnosis appear to be promising enough to warrant further
      investigation. Another promising nonpharmacological therapy, currently under
      investigation, involves a stellate ganglion block.

PMID- 21072307
TI  - Optimal management of perimenopausal depression.
AB  - Only recently has the perimenopause become recognized as a time when women are at
      risk for new onset and recurrence of major depression. Untreated depression at
      this time not only exacerbates the course of a depressive illness, but also puts
      women at increased risk for sleep disorders, cardiovascular disease, diabetes,
      and osteoporosis. Although antidepressant medication is the mainstay of
      treatment, adjunctive therapy, especially with estrogen replacement, may be
      indicated in refractory cases, and may speed the onset of antidepressant action.
      Many, but not all, studies, report that progesterone antagonizes the beneficial
      effects of estrogen. Although some antidepressants improve vasomotor symptoms, in
      general they are not as effective as estrogen alone for relieving these symptoms.
      Estrogen alone, however, does not generally result in remission of major
      depression in most (but not all) studies, but may provide benefit to some women
      with less severe symptoms if administered in therapeutic ranges. The selective
      serotonin reuptake inhibitors (SSRIs) in addition to estrogen are usually more
      beneficial in improving mood than SSRIs or estrogen treatment alone for major
      depression, whereas the selective norepinephrine and serotonin reuptake
      inhibitors do not require the addition of estrogen to exert their antidepressant
      effects in menopausal depression. In addition to attention to general health,
      hormonal status, and antidepressant treatment, the optimal management of
      perimenopausal depression also requires attention to the individual woman's
      psychosocial and spiritual well being.

PMID- 21072309
TI  - Management of hypoactive sexual desire disorder in women: current and emerging
      therapies.
AB  - Hypoactive sexual desire disorder (HSDD) is a common multifactorial condition
      which is characterized by a decrease in sexual desire that causes marked personal
      distress and/or interpersonal difficulty. The general idea that HSDD is a sexual
      dysfunction difficult to treat is due to the large number of potential causes and
      contributing factors. Indeed, a balanced approach comprising both biological and
      psycho-relational factors is mandatory for accurate diagnosis and tailored
      management in clinical practice. There are currently no approved pharmacological
      treatments for premenopausal women with HSDD, while transdermal testosterone is
      approved in Europe for postmenopausal women who experience HSDD as a result of a
      bilateral oophorectomy. Even though the role of sex hormones in modulating the
      sexual response during the entire reproductive life span of women is crucial, a
      better understanding of the neurobiological basis of sexual desire supports the
      idea that selective psychoactive agents may be proposed as nonhormonal treatments
      to restore the balance between excitatory and inhibitory stimuli leading to a
      normal sexual response cycle. We conclude that the ideal clinical approach to
      HSDD remains to be established in term of efficacy and safety, and further
      research is needed to develop specific hormonal and nonhormonal pharmacotherapies
      for individualized care in women.

PMID- 21072310
TI  - The influence of health-seeking behavior on the incidence and perinatal outcome
      of umbilical cord prolapse in Nigeria.
AB  - OBJECTIVES: To determine the influence of health-seeking behavior of urban women
      in South-West Nigeria on the incidence and perinatal outcome of umbilical cord
      prolapse (UCP). METHODS: A retrospective study comparing two groups of urban
      women using information extracted from medical records of patients who had UCP,
      and were managed at the University College Hospital Ibadan, Nigeria from
      January1st 1995 to December 31st 2005. The data was analyzed using SPSS software
      (version 15). Analysis included simple tabulation, proportion and comparison of
      incidence, perinatal morbidity, and mortality of UCP between the two groups of
      women using Chi-square or Fisher's exact test. Odds ratio (OR) and 95% confidence
      intervals (CI) were calculated whenever necessary. P-value of 0.05 or less was
      statistically significant. RESULTS: Women without prenatal care were more likely
      to have fetuses with UCP (54, 75%), than in women who had prenatal care (18,
      25%). The risk of perinatal death from UCP was higher in women without prenatal
      care, as compared with those who received prenatal care (OR 3.02, 95% CI: 0.879
      to 10.356; P-value = 0.061). The risk of perinatal morbidity and neonatal
      intensive care admission was also higher among women without prenatal care as
      compared with women who received prenatal care (OR 4.09, 95% CI: 1.03 to 16.30; P
      value = 0.041). The overall perinatal mortality rate in the study population was
      403 per 1000 total births, and this was five times more than that of the hospital
      perinatal mortality rate of 80 per 1000 total births during the study period. The
      perinatal mortality rate was higher among women without prenatal care, 463 per
      1000 total births, as compared with 222 per 1000 total births in women who
      received prenatal care. Perinatal death before arrival at the hospital is less
      likely to occur in women with prenatal care when compared with women without
      prenatal care (OR 0.0635; 95% CI: 0.0052 to 0.776; P-value = 0.03). CONCLUSION: A
      high index of suspicion and an identification of risk factors, with early
      diagnosis, prompt intervention, and provision of health care facilities can
      reduce the incidence and poor outcome of UCP in developing countries.

PMID- 21072308
TI  - Estrogens of multiple classes and their role in mental health disease mechanisms.
AB  - Gender and sex hormones can influence a variety of mental health states,
      including mood, cognitive development and function, and vulnerability to
      neurodegenerative diseases and brain damage. Functions of neuronal cells may be
      altered by estrogens depending upon the availability of different physiological
      estrogenic ligands; these ligands and their effects vary with life stages, the
      genetic or postgenetic regulation of receptor levels in specific tissues, or the
      intercession of competing nonphysiological ligands (either intentional or
      unintentional, beneficial to health or not). Here we review evidence for how
      different estrogens (physiological and environmental/dietary), acting via
      different estrogen receptor subtypes residing in alternative subcellular
      locations, influence brain functions and behavior. We also discuss the families
      of receptors and transporters for monoamine neurotransmitters and how they may
      interact with the estrogenic signaling pathways.

PMID- 21072312
TI  - The use of anti-TNFalpha medications for rheumatologic disease in pregnancy.
AB  - Anti-TNFalpha medications have led to vast improvements in the treatment of
      inflammatory conditions, including rheumatoid arthritis and Crohn's disease. As
      these diseases often afflict women in their reproductive years, the safety of
      these drugs during pregnancy is an important issue. Prospectively collected data
      thus far appear to be reassuring; however an analysis of the FDA-reported
      anomalies has raised some questions. It appears that significant levels of these
      drugs cross the placenta as the pregnancy nears term, but little is passed
      through breast milk. Prior to using these medications during pregnancy, the risks
      and benefits of these drugs, other treatment options, and the ongoing
      inflammatory condition all must be carefully weighed by both doctor and patient.

PMID- 21072314
TI  - Cervical cancer screening: knowledge, health perception and attendance rate among
      Hong Kong Chinese women.
AB  - PURPOSE: Cervical cancer screening has been consistently shown to be effective in
      reducing the incidence rate and mortality from cervical cancer. However, cervical
      screening attendance rates are still far from satisfactory in many countries.
      Strategies, health promotion and education programs need to be developed with
      clear evidence of the causes and factors relating to the low attendance rate. The
      study aims to assess the prediction of cervical screening attendance rate by
      Chinese women's knowledge about cervical cancer and cervical screening as well as
      their perception of health. PATIENTS AND METHODS: A survey with self-reported
      questionnaires was conducted on 385 Chinese women recruited from a community
      clinic in Hong Kong. Participants were Chinese women, Hong Kong residents, aged
      18-65 years, able to read Chinese or English, and were not pregnant. RESULTS:
      Women aged 37 years or less, with at least tertiary education, who perceived
      having control over their own health and had better knowledge on risk factors,
      were more likely to attend cervical cancer screening. Many participants had
      adequate general knowledge but were unable to identify correct answers on the
      risk factors. CONCLUSION: Health promotion efforts need to focus on increasing
      women's knowledge on risk factors and enhancing their perceived health control by
      providing more information on the link between screening and early detection with
      lower incidence rates and mortality from cervical cancer.

PMID- 21072311
TI  - Partner violence during pregnancy: prevalence, effects, screening, and
      management.
AB  - The purpose of this review is to provide an overview of the current state of
      knowledge regarding the experience of intimate partner violence (IPV) during
      pregnancy. Pregnancy IPV is a significant problem worldwide, with rates varying
      significantly by country and maternal risk factors. Pregnancy IPV is associated
      with adverse newborn outcomes, including low birth weight and preterm birth. Many
      mechanisms for how IPV may impact birth outcomes have been proposed and include
      direct health, mental health, and behavioral effects, which all may interact.
      Screening for IPV during pregnancy is essential, yet due to time constraints and
      few clear recommendations for assessment, many prenatal providers do not
      routinely inquire about IPV, or even believe they should. More training is needed
      to assist health care providers in identifying and managing pregnancy IPV, with
      additional research needed to inform effective interventions to reduce the rates
      of pregnancy IPV and resultant outcomes.

PMID- 21072313
TI  - Long-term safety, efficacy, and patient acceptability of the intrauterine Copper
      T-380A contraceptive device.
AB  - The intrauterine device (IUD), primarily in the form of the copper IUD, is used
      by more than 150 million women around the world, making it the most widely used
      reversible method of contraception. With a remarkably low failure rate of less
      than 1 per 100 women in the first year of use, the Copper T-380A is in the top
      tier of contraceptives in terms of efficacy. Risks of utilization include
      perforation and an increased risk of infection in the first 20 days following
      insertion. Overall, the number of adverse events is low, making the Copper T-380A
      a very safe contraceptive method. The most common reasons for the discontinuation
      of this method are menstrual bleeding and dysmenorrhea. However, cumulative
      discontinuation rates of Copper T-380A are lower than that have been reported for
      other methods, indicating that the Copper T-380A is highly acceptable to women.
      After 5 years, approximately 50% of all women, who have a Copper T-380A inserted,
      will continue to use this highly effective contraceptive method.

PMID- 21072315
TI  - Prevalence of anemia in women with asymptomatic malaria parasitemia at first
      antenatal care visit at the University of Calabar Teaching Hospital, Calabar,
      Nigeria.
AB  - BACKGROUND: Anemia in pregnancy in malaria endemic areas is a public health
      challenge that has contributed either directly or indirectly to maternal
      morbidity and mortality in our environment. Anemia and malaria during pregnancy
      are highly preventable and treatable. OBJECTIVE: The aim of this study is to
      assess the prevalence of anemia in asymptomatic malaria parasitemic women at
      first antenatal visit in a tertiary hospital facility. METHOD: The study was
      conducted at the antenatal clinic of the University of Calabar Teaching Hospital,
      Calabar, Nigeria over a three-month period. Five hundred and forty-five pregnant
      women were recruited after obtaining an informed consent. A structured
      questionnaire was administered to each participant and two thin and thick blood
      films were used to identify the malaria parasites and estimate density. The
      average of two packed cell volumes at booking was determined using two capillary
      tubes and read from a Hawksleys microhematocrit reader. RESULTS: A total of 545
      pregnant women participated in the study. The mean ages of primigravidas and
      multigravidas were 21.4 +/- 3.1 and 24.3 +/- 4.0 years. Two hundred and ninety
      (53.2%) were primigravidas while 255 (46.8%) were multigravidas. The parasite
      density in primigravidas was 1297 +/- 1234 while that for multigravidas was 661
      +/- 497 (t = 7.7, P < 0.001). The prevalence of anemia in the study population
      was 59.6%. There was no statistically significant difference in the prevalence of
      anemia among the primigravidas (60.3%) and the multigravidas (58.8%) (chi(2) =
      1.3, P = 0.08). There was a statistically significant association between
      severity of parasitemia and degree of anemia (chi(2) = 441.1, P < 0.001). There
      was a statistically significant association between antimalarials use before
      booking and severity of parasitemia (chi(2) = 36.52, P < 0.001). CONCLUSION:
      Anemia at first antenatal booking was significantly associated with malaria
      parasitemia. Routine screening for anemia and malaria parasites at booking,
      prompt parasite clearance, use of intermittent preventive treatment (IPT) during
      pregnancy and correction of anemia can reduce the prevalence of malaria related
      anemia and obstetric complications associated with it.

PMID- 21072316
TI  - A Bayesian model for longitudinal count data with non-ignorable dropout.
AB  - Asthma is an important chronic disease of childhood. An intervention programme
      for managing asthma was designed on principles of self-regulation and was
      evaluated by a randomized longitudinal study.The study focused on several
      outcomes, and, typically, missing data remained a pervasive problem. We develop a
      pattern-mixture model to evaluate the outcome of intervention on the number of
      hospitalizations with non-ignorable dropouts. Pattern-mixture models are not
      generally identifiable as no data may be available to estimate a number of model
      parameters. Sensitivity analyses are performed by imposing structures on the
      unidentified parameters.We propose a parameterization which permits sensitivity
      analyses on clustered longitudinal count data that have missing values due to non
      ignorable missing data mechanisms. This parameterization is expressed as ratios
      between event rates across missing data patterns and the observed data pattern
      and thus measures departures from an ignorable missing data mechanism.
      Sensitivity analyses are performed within a Bayesian framework by averaging over
      different prior distributions on the event ratios. This model has the advantage
      of providing an intuitive and flexible framework for incorporating the
      uncertainty of the missing data mechanism in the final analysis.

PMID- 21072317
TI  - POSTURE MATCHING AND ELASTIC REGISTRATION OF A MOUSE ATLAS TO SURFACE TOPOGRAPHY
      RANGE DATA.
AB  - Estimation of internal mouse anatomy is required for quantitative bioluminescence
      or fluorescence tomography. However, only surface range data can be recovered
      from all-optical systems. These data are at times sparse or incomplete. We
      present a method for fitting an elastically deformable mouse atlas to surface
      topographic range data acquired by an optical system. In this method, we first
      match the postures of a deformable atlas and the range data of the mouse being
      imaged. This is achieved by aligning manually identified landmarks. We then
      minimize the asymmetric L(2) pseudo-distance between the surface of the
      deformable atlas and the surface topography range data. Once this registration is
      accomplished, the internal anatomy of the atlas is transformed to the coordinate
      system of the range data using elastic energy minimization. We evaluated our
      method by using it to register a digital mouse atlas to a surface model produced
      from a manually labeled CT mouse data set. Dice coefficents indicated excellent
      agreement in the brain and heart, with fair agreement in the kidneys and bladder.
      We also present example results produced using our method to align the digital
      mouse atlas to surface range data.

PMID- 21072318
TI  - Identification of glycoproteins from mouse skin tumors and plasma.
AB  - Plasma has been the focus of testing different proteomic technologies for the
      identification of biomarkers due to its ready accessibility. However, it is not
      clear if direct proteomic analysis of plasma can be used to discover new marker
      proteins from tumor that are associated with tumor progression. Here, we reported
      that such proteins can be detected in plasma in a chemical induced skin cancer
      mouse model. We analyzed glycoproteins from both benign papillomas and malignant
      carcinomas from mice using our recently developed platform, solid-phase
      extraction of glycopeptides (SPEG) and mass spectrometry, and identified 463
      unique N-linked glycosites from 318 unique glycoproteins. These include most
      known extracellular proteins that have been reported to play roles in skin cancer
      development such as thrombospondin, cathepsins, epidermal growth factor receptor,
      cell adhesion molecules, cadherins, integrins, tuberin, fibulin, TGFbeta
      receptor, etc. We further investigated whether these tumor proteins could be
      detected in plasma from tumor bearing mice using isotope labeling and 2D-LC-MALDI
      MS/MS. Two tumor glycoproteins, Tenascin-C and Arylsulfatase B, were identified
      and quantified successfully in plasma from tumor bearing mice. This result
      indicates that analysis of tumor associated proteins in tumors and plasma by
      method using glycopeptide capture, isotopic labeling, and mass spectrometry can
      be used as a discovery tool to identify candidate tumor proteins that may be
      detected in plasma.

PMID- 21072319
TI  - The novel estrogen-induced gene EIG121 regulates autophagy and promotes cell
      survival under stress.
AB  - We previously identified a novel estrogen-induced gene, EIG121, as being
      differentially regulated in endometrioid and nonendometrioid endometrial
      carcinoma. The function of EIG121 was unknown. Using a tetracycline-inducible
      system, we found that overexpression of EIG121, but not of LacZ, caused a
      profound suppression of cell growth. Subcellular fractionation and
      immunofluroscent labeling indicated that EIG121 was a transmembrane protein
      localized in the plasma membrane-late endosome-lysosome compartments. Deletion of
      the putative transmembrane domain abolished the membrane association. In cells
      overexpressing EIG121, cytoplasmic vacuoles accumulated after EIG121 induction,
      and the autophagosome marker LC3 translocated into punctuate, dot-like
      structures. Electron microscopy revealed that in cells overexpressing EIG121,
      autophagosomes were markedly increased. Overexpression of EIG121 also increased
      the cells containing acidic vesicles and induced lysosomal degradation of long
      lived proteins. In MCF-7 cells, both EIG121 and LC3 were rapidly degraded by a
      lysosomal mechanism after starvation. Knockdown of EIG121 blocked starvation
      induced LC3 degradation. By itself, knockdown of EIG121 did not affect cell
      survival. When combined with starvation or cytotoxic agents, EIG121 knockdown
      greatly increased apoptosis. Our results suggest that EIG121 is associated with
      the endosome-lysosome compartments and may have an important role in autophagy.
      Under unfavorable conditions such as starvation and exposure to cytotoxic agents,
      EIG121 may protect cells from cell death by upregulating the autophagy pathway.

PMID- 21072320
TI  - PET Performance Evaluation of an MR-Compatible PET Insert.
AB  - A magnetic resonance (MR) compatible positron emission tomography (PET) insert
      has been developed in our laboratory for simultaneous small animal PET/MR
      imaging. This system is based on lutetium oxyorthosilicate (LSO) scintillator
      arrays with position-sensitive avalanche photodiode (PSAPD) photodetectors. The
      PET performance of this insert has been measured. The average reconstructed image
      spatial resolution was 1.51 mm. The sensitivity at the center of the field of
      view (CFOV) was 0.35%, which is comparable to the simulation predictions of
      0.40%. The average photopeak energy resolution was 25%. The scatter fraction
      inside the MRI scanner with a line source was 12% (with a mouse-sized phantom and
      standard 35 mm Bruker 1H RF coil), 7% (with RF coil only) and 5% (without phantom
      or RF coil) for an energy window of 350-650 keV. The front-end electronics had a
      dead time of 390 ns, and a trigger extension dead time of 7.32 MUs that degraded
      counting rate performance for injected doses above ~0.75 mCi (28 MBq). The peak
      noise-equivalent count rate (NECR) of 1.27 kcps was achieved at 290 MUCi (10.7
      MBq). The system showed good imaging performance inside a 7-T animal MRI system;
      however improvements in data acquisition electronics and reduction of the
      coincidence timing window are needed to realize improved NECR performance.

PMID- 21072321
TI  - Substitutional A-to-I RNA editing.
AB  - Adenosine-to-inosine (A-to-I) editing catalyzed by adenosine deaminases acting on
      RNA (ADARs) entails the chemical conversion of adenosine residues to inosine
      residues within double-stranded RNA (dsRNA) substrates. Inosine base pairs as
      guanosine and A-to-I editing can therefore alter the structure and base pairing
      properties of the RNA molecule. This has a biological significance in controlling
      the amount of functional RNA molecules in the cell, in expanding the
      functionality of a limited set of transcripts, and in defending the cell against
      certain RNA viruses. A-to-I editing is not limited to any specific type of RNA
      substrate. Instead, it can affect any RNA molecule able to attain the required
      double-stranded structure. This includes microRNAs, small interfering RNAs, viral
      RNAs, and messenger RNAs with potential for recoding events and splice site
      modifications.

PMID- 21072323
TI  - Overexpression of Colligin 2 in Glioma Vasculature is Associated with
      Overexpression of Heat Shock Factor 2.
AB  - In previous studies we found expression of the protein colligin 2 (heat shock
      protein 47 (HSP47), SERPINH1) in glioma neovasculature while not in normal brain
      tissue. Generally, the regulation of heat shock gene expression in eukaryotes is
      mediated by heat shock factors (HSF). In mammals, three heat shock transcription
      factors, HSF-1, -2, and -4, have been isolated. Here we investigated the relation
      between the expression of colligin 2 and these heat shock factors at the mRNA
      level using real-time reverse transcriptase PCR (qRT-PCR) in different grades of
      astrocytic tumorigenesis, viz., low-grade glioma and glioblastoma. Endometrium
      samples, representing physiological angiogenesis, were included as controls.
      Since colligin 2 is a chaperon for collagens, the gene expression of collagen I
      (COL1A1) was also investigated. The blood vessel density of the samples was
      monitored by expression of the endothelial marker CD31 (PECAM1). Because NG2
      immunopositive pericytic cells are involved in glioma neovascularization, the
      expression of NG2 (CSPG4) was also measured.We demonstrate overexpression of HSF2
      in both stages of glial tumorigenesis (reaching significance only in low-grade
      glioma) and also minor elevated levels of HSF1 as compared to normal brain. There
      were no differences in expression of HSF4 between low-grade glioma and normal
      brain while HSF4 was downregulated in glioblastoma. In the endometrium samples,
      none of the HSFs were upregulated. In the low-grade gliomas SERPINH appeared to
      be slightly overexpressed with a parallel 4-fold upregulation of COL1A1, while in
      glioblastoma there was over 5-fold overexpression of SERPINH1 and more than 150
      fold overexpression of COL1A1. In both the lowgrade gliomas and the glioblastomas
      overexpression of CSPG4 was found and overexpression of PECAM1 was only found in
      the latter. Our data suggest that the upregulated expression of colligin 2 in
      glioma is accompanied by upregulation of COL1A1, CSPG4, HSF2 and to a lesser
      extent, HSF1. Further studies will unravel the association of these factors with
      colligin 2 expression, possibly leading to keys for therapeutic intervention.

PMID- 21072322
TI  - Language and Dementia: Neuropsychological Aspects.
AB  - This article reviews recent evidence for the relationship between extralinguistic
      cognitive and language abilities in dementia. A survey of data from
      investigations of three dementia syndromes (Alzheimer's disease, semantic
      dementia and progressive nonfluent aphasia) reveals that, more often than not,
      deterioration of conceptual organization appears associated with lexical
      impairments, whereas impairments in executive function are associated with
      sentence- and discourse-level deficits. These connections between extralinguistic
      functions and language ability also emerge from the literature on cognitive
      reserve and bilingualism that investigates factors that delay the onset and
      possibly the progression of neuropsychological manifestation of dementia.

PMID- 21072324
TI  - Omega-6 fat supplementation alters lipogenic gene expression in bovine
      subcutaneous adipose tissue.
AB  - In contrast to rodents, adipose tissue serves as the major site of lipogenesis
      and storage reservoir for excess dietary energy in cattle. Research in rodents
      shows that adding corn oil (57% C18:2 n-6) to the diet alters lipogenesis
      enhancing deposition of omega-6 fatty acids. This study examines changes in
      lipogenic gene expression of subcutaneous adipose tissue from eighteen steers fed
      increasing levels of dietary corn oil [0 (NONE), 0.31 kg/d (MED) and 0.62 kg/d
      (HI)] using two platforms, qPCR and microarray. The results show that MED level
      of oil supplementation up-regulates gene expression of key lipogenic enzymes but
      that as oil supplementation reaches HI level mRNA encoding lipogenic enzymes
      responsible for de novo synthesis and desaturation are down-regulated. Changes in
      specific lipogenic mRNA levels are correlated with changes in tissue fatty acid
      composition where de novo and desatured fatty acids were reduced with the highest
      level of oil supplementation.

PMID- 21072326
TI  - Arrhythmia models: in vivo, in vitro and in silico.

PMID- 21072325
TI  - Myc Function in Drosophila.
AB  - Myc proteins control several cellular processes, including proliferation and
      growth, and they play an important role in human tumorigenesis. Several years
      ago, single homologs of Myc, its interaction partner Max, and its antagonist Mnt
      were identified in Drosophila melanogaster. Here, we review the function of this
      so-called Max network in fruit flies, with a particular emphasis on its most
      obvious biological activity: the control of cellular and organismal growth. We
      describe the molecular basis for this growth function, as well as the interaction
      of Myc with other pathways known to control growth, the insulin, TOR, and hippo
      pathways. In addition, Drosophila Myc also controls DNA replication and
      influences apoptosis, both cell-autonomously and non-autonomously, in a process
      known as cell competition. In the future, we expect that further functions of Myc
      will be uncovered and that genetic approaches will increasingly be used to
      characterize the evolutionarily conserved molecular mechanism of Myc action, thus
      also benefitting our understanding of Myc biology in vertebrates.

PMID- 21072327
TI  - High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction
      of Enolate-Stabilized Enol Carbonates.
AB  - The use of high-throughput screening allowed for the optimization of reaction
      conditions for the palladium-catalyzed asymmetric decarboxylative alkylation
      reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction
      solvent and to an electron-deficient PHOX derivative as ligand from our standard
      reaction conditions improved the enantioselectivity for the alkylation of a ketal
      protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar
      improvements in enantioselectivity were seen for a beta-keto-ester derived- and
      an alpha-phenyl cyclohexanone-derived enol carbonate.

PMID- 21072328
TI  - Analysis of Bonding between Conjugated Organic Molecules and Noble Metal Surfaces
      Using Orbital Overlap Populations.
AB  - The electronic structure of metal-organic interfaces is of paramount importance
      for the properties of organic electronic and single-molecule devices. Here, we
      use so-called orbital overlap populations derived from slab-type band-structure
      calculations to analyze the covalent contribution to the bonding between an
      adsorbate layer and a metal. Using two prototypical molecules, the strong
      acceptor 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) on Ag(111)
      and the strong donor 1H,1'H-[4,4']bipyridinylidene (HV0) on Au(111), we present
      overlap populations as particularly versatile tools for describing the metal
      organic interaction. Going beyond traditional approaches, in which overlap
      populations are represented in an atomic orbital basis, we also explore the use
      of a molecular orbital basis to gain significant additional insight. On the basis
      of the derived quantities, it is possible to identify the parts of the molecules
      responsible for the bonding and to analyze which of the molecular orbitals and
      metal bands most strongly contribute to the interaction and where on the energy
      scale they interact in bonding or antibonding fashion.

PMID- 21072329
TI  - Using Selectively Applied Accelerated Molecular Dynamics to Enhance Free Energy
      Calculations.
AB  - Accelerated molecular dynamics (aMD) has been shown to enhance conformational
      space sampling relative to classical molecular dynamics; however, the exponential
      reweighting of aMD trajectories, which is necessary for the calculation of free
      energies relating to the classical system, is oftentimes problematic, especially
      for systems larger than small poly peptides. Here, we propose a method of
      accelerating only the degrees of freedom most pertinent to sampling, thereby
      reducing the total acceleration added to the system and improving the convergence
      of calculated ensemble averages, which we term selective aMD. Its application is
      highlighted in two biomolecular cases. First, the model system alanine dipeptide
      is simulated with classical MD, all-dihedral aMD, and selective aMD, and these
      results are compared to the infinite sampling limit as calculated with
      metadynamics. We show that both forms of aMD enhance the convergence of the
      underlying free energy landscape by 5-fold relative to classical MD; however,
      selective aMD can produce improved statistics over all-dihedral aMD due to the
      improved reweighting. Then we focus on the pharmaceutically relevant case of
      computing the free energy of the decoupling of oseltamivir in the active site of
      neuraminidase. Results show that selective aMD greatly reduces the cost of this
      alchemical free energy transformation, whereas all-dihedral aMD produces
      unreliable free energy estimates.

PMID- 21072330
TI  - Social Influence and Selection Processes as Predictors of Normative Perceptions
      and Alcohol Use Across the Transition to College.
AB  - Research indicates that social influences impact college alcohol consumption.
      However, little work has addressed how selection processes may serve as an
      influential factor predicting alcohol use in this population. A model of
      influence and selection processes contributing to alcohol use across the
      transition to college was examined using structural equation modeling among a
      sample of late adolescents (N=193). Results indicate selection processes occur as
      students transition into college and have the opportunity to seek out and join
      new friend circles, while peer influence occurs once students have settled within
      a circle of friends at college. Implications for prevention are discussed.

PMID- 21072331
TI  - The Ribosome Comes Alive.
AB  - This essay is a reflection on the ways the X-ray structures of the ribosome are
      helping in the interpretation of cryogenic electron microscopy (cryo-EM) density
      maps showing the translating ribosome in motion. Through advances in
      classification methods, cryo-EM and single-particle reconstruction methods have
      recently evolved to the point where they can yield an array of structures from a
      single sample ("story in a sample"), providing snapshots of an entire subprocess
      of translation, such as translocation or decoding.

PMID- 21072332
TI  - New nanostructured electrochemical biosensors based on three-dimensional (3
      mercaptopropyl)-trimethoxysilane network.
AB  - The design and characterization of a new nanostructured organic-inorganic hybrid
      material and its application to L-lactic acid determination are described. This
      material is based on the integration of the enzyme lactate oxidase (LOx) and gold
      nanoparticles (AuNPs) into a sol-gel 3D polymeric network derived from (3
      mercaptopropyl)-trimethoxysilane (MPTS) previously formed onto a gold surface.
      MPTS presents the advantage of forming a 3D polymeric network containing a large
      number of thiol tail groups distributed throughout its structure that enable both
      its anchoring onto gold surfaces and the AuNPs incorporation. Moreover, this
      matrix provides a biocompatible environment that preserves the catalytic activity
      of LOx after its immobilization and allows the incorporation of a high amount of
      enzyme, which is expected to improve the sensitivity of the final biosensing
      device. Characterization of the designed biosensing platform was performed using
      quartz crystal microbalance (QCM), scanning electron microscopy (SEM) and atomic
      force microscopy (AFM) techniques. From the conjunction of these techniques,
      information about (i) the kinetic of LOx adsorption process in real time, (ii)
      the amount of LOx incorporated into the network, and (iii) the morphological
      characteristics at the nanometre level of the designed biosensing material was
      obtained. This information is very useful on the development of successful
      biosensing devices. Finally, the response of the biosensor to L-lactic acid was
      evaluated. The biosensor responds linearly to L-lactic acid in the range of 50 uM
      to 0.25 mM, with a sensitivity of 3.4 uA mM(-1) and a detection limit of 4.0 uM.

PMID- 21072333
TI  - Analytical method for parameterizing the random profile components of
      nanosurfaces imaged by atomic force microscopy.
AB  - The functional properties of many technological surfaces in biotechnology,
      electronics, and mechanical engineering depend to a large degree on the
      individual features of their nanoscale surface texture, which in turn is a
      function of the surface manufacturing process. Among these features, the surface
      irregularities and self-similarity structures at different spatial scales,
      especially in the range of 1 to 100 nm, are of high importance because they
      greatly affect the surface interaction forces acting at a nanoscale distance. An
      analytical method for parameterizing the surface irregularities and their
      correlations in nanosurfaces imaged by atomic force microscopy (AFM) is proposed.
      In this method, flicker noise spectroscopy--a statistical physics approach--is
      used to develop six nanometrological parameters characterizing the high-frequency
      contributions of jump- and spike-like irregularities into the surface texture.
      These contributions reflect the stochastic processes of anomalous diffusion and
      inertial effects, respectively, in the process of surface manufacturing. The AFM
      images of the texture of corrosion-resistant magnetite coatings formed on low
      carbon steel in hot nitrate solutions with coating growth promoters at different
      temperatures are analyzed. It is shown that the parameters characterizing surface
      spikiness are able to quantify the effect of process temperature on the corrosion
      resistance of the coatings. It is suggested that these parameters can be used for
      predicting and characterizing the corrosion-resistant properties of magnetite
      coatings.

PMID- 21072334
TI  - Electrocatalytic detection of polysaccharides at picomolar concentrations.
AB  - Electroinactive polysaccharides (PS) modified by osmium(VI) complexes with
      nitrogenous ligands produce redox couples at carbon and mercury electrodes. We
      show that PS adducts with Os(VI) 2,2'-bipyridine produce at ~-1.2 V (against
      Ag/AgCl/3 M KCl electrode) an additional peak at mercury and solid amalgam
      electrodes. This peak is due to the catalytic hydrogen evolution, allowing
      detection of PS (such as dextran and mannan) at picomolar concentrations.

PMID- 21072335
TI  - Cyclometalated platinum(II) complexes as topoisomerase IIalpha poisons.
AB  - A platinum(II)-based major groove binder [Pt(II)(C^N)(C=NR)(2)](+) (HC^N = 2
      phenylpyridine (phpy), R = 2-naphthyl) was identified as a potent human
      topoisomerase IIalpha poison. It stabilizes the covalent TopoIIalpha-DNA cleavage
      complex and induces cancer cell death with potency significantly higher than the
      widely clinically used TopoIIalpha poison Vp-16.

PMID- 21072336
TI  - Cytosolic metal handling in plants: determinants for zinc specificity in metal
      transporters and metallothioneins.
AB  - The handling of trace elements by plants plays a fundamental role in food
      security and safety. Therefore, there is a need to understand the mechanisms that
      govern metal ion trafficking in plants. The past decade has seen an immense
      expansion of knowledge on metal ion transport in a variety of biological systems
      including plants, but as for other organisms, the mechanisms for intracellular
      zinc trafficking remain enigmatic. The current report highlights recent advances
      in understanding zinc transport in plants and in identifying the biomolecules
      involved in this process. A particular focus is put on pinpointing determinants
      for zinc specificity, and we also highlight areas in need of development.
      Reliable experimental speciation data are a first step towards systems biology
      approaches to mineral nutrition in plants-but there is also a need to understand
      molecular details. One intriguing question, in particular in the context of
      predicting protein function, concerns how discrimination between metal ions in a
      biological system functions.

PMID- 21072337
TI  - Structure and antibacterial activity of the silver(I) complex of 2
      aminophenoxazine-3-one.
AB  - The crystal structure and antibacterial activity of the first metal complex of 2
      aminophenoxazine-3-one is reported. We describe the silver(i) complex of this
      important biological molecule and show that the binding mode is through the
      phenoxazine ring nitrogen. A new synthetic route to 2-aminophenoxazine-3-one is
      also reported.

PMID- 21072338
TI  - Study of the Se-containing metabolomes in Se-rich yeast by size-exclusion-cation
      exchange HPLC with the parallel ICP MS and electrospray orbital ion trap
      detection.
AB  - Strong cation exchange HPLC with the parallel ICP MS and electrospray hybrid
      linear ion trap quadrupole orbital trap mass spectrometry (ESI Orbitrap MS)
      detection was developed for the study of the metabolomic pattern of selenium in
      selenium-rich yeast. The mobile phase composition (gradient of ammonium formate
      in 20% methanol) was optimized to obtain separation in conditions guaranteeing
      the identical ICP MS sensitivity during the entire chromatographic run and the
      compatibility with electrospray ionization. Twenty seven Se-containing
      metabolites observed in the HPLC-ICP MS chromatogram were identified by ESI
      Orbitrap MS based on the Se isotopic pattern, the accurate molecular mass, and
      the multistage fragmentation patterns. The method allowed for the first time the
      correlation of the differences observed in HPLC-ICP MS chromatography of water
      extracts of Se-rich yeast samples from different manufacturers with the identity
      of the eluted compounds determined by ESI MS.

PMID- 21072339
TI  - Probing the metal-homeostatis effects of the administration of chromium(vi) to
      mice by ICP MS and size-exclusion chromatography-ICP MS.
AB  - Concentrations of chromium, copper, iron, manganese and zinc were determined in
      liver, kidney, brain, lung, heart and testis of mouse following intraperitoneal
      injection of hexavalent chromium [Cr(vi)] at a single dose of 8.0 mg Cr/kg. As
      result, chromium concentrations increased ca. 40-fold in liver and kidney and by
      a factor of 3-5 in all the other tissues. The homeostasis of Cu, Fe, Mn and Zn
      was also affected. The element molecular weight distribution was evaluated in the
      cytosols of the different mouse organs by size-exclusion chromatography (Superdex
      75) with UV-VIS and ICP-MS detection. The administration of Cr(vi) resulted in
      differences in the elution profiles of Fe, Mn, Cu and Zn-protein complexes.
      Bioinduced Mn, Fe and Zn-binding proteins could be detected in some tissues,
      especially in liver and kidney. Different molecular weight fractions containing
      chromium were heartcut and submitted to tryptic digestion prior to MALDI MS
      analysis. Cr-peptide complexes could be obtained both in non-denaturing and in
      denaturing (in the presence of urea and DTT) conditions. They were isolated by
      size-exclusion chromatography with a smaller separation range (Superdex Peptide)
      but could not be identified by MALDI MS.

PMID- 21072340
TI  - Metallochaperone-like genes in Arabidopsis thaliana.
AB  - A complete inventory of metallochaperone-like proteins containing a predicted HMA
      domain in Arabidopsis revealed a large family of 67 proteins. 45 proteins, the
      HIPPs, have a predicted isoprenylation site while 22 proteins, the HPPs, do not.
      Sequence comparisons divided the proteins into seven major clusters (I-VII).
      Cluster IV is notable for the presence of a conserved Asp residue before the
      CysXXCys, metal binding motif, analogous to the Zn binding motif in E. coli ZntA.
      HIPP20, HIPP21, HIPP22, HIPP26 and HIPP27 in Cluster IV were studied in more
      detail. All but HIPP21 could rescue the Cd-sensitive, ycf1 yeast mutant but
      failed to rescue the growth of zrt1zrt2, zrc1cot1 and atx1 mutants. In
      Arabidopsis, single and double mutants did not show a phenotype but the
      hipp20/21/22 triple mutant was more sensitive to Cd and accumulated less Cd than
      the wild-type suggesting the HIPPs can have a role in Cd-detoxification, possibly
      by binding Cd. Promoter-GUS reporter expression studies indicated variable
      expression of these HIPPs. For example, in roots, HIPP22 and HIPP26 are only
      expressed in lateral root tips while HIPP20 and HIPP25 show strong expression in
      the root vasculature.

PMID- 21072341
TI  - Quantification of phytochelatins in Chlamydomonas reinhardtii using ferrocene
      based derivatization.
AB  - A method for the identification and quantification of canonic and isoforms of
      phytochelatins (PCs) from Chlamydomonas reinhardtii was developed. After
      disulfide reduction with tris(2-carboxyethyl)phosphine (TCEP) PCs were
      derivatized with ferrocenecarboxylic acid (2-maleimidoyl)ethylamide (FMEA) in
      order to avoid oxidation of the free thiol functions during analysis. Liquid
      chromatography (LC) coupled to electrospray mass spectrometry (ESI-MS) and
      inductively coupled plasma-mass spectrometry (ICP-MS) was used for rapid and
      quantitative analysis of the precolumn derivatized PCs. PC(2-4), CysGSH, CysPC(2
      4), CysPC(2)desGly, CysPC(2)Glu and CysPC(2)Ala were determined in the algal
      samples depending on the exposure of the cells to cadmium ions.

PMID- 21072342
TI  - Synthesis, characterization and biological evaluation of In(III) complexes
      anchored by DOTA-like chelators bearing a quinazoline moiety.
AB  - Following previous studies with a DOTA-like bifunctional chelator (H(3)L1)
      containing an ethylenic linker between the macrocycle backbone and a quinazoline
      pharmacophore, we synthesized and fully characterized a congener macrocyclic
      ligand (H(3)L2) having a longer, five-carbon spacer for the linkage of the
      quinazoline moiety. Both H(3)L1 and H(3)L2 were used to prepare indium(III)
      complexes aiming at their evaluation as radioactive probes for in vivo targeting
      of EGFR-TK. The protonation constants (log K(Hi)) of H(3)L2 were determined by
      potentiometry and UV-Vis spectrophotometry and the values found are 12.18, 9.74,
      4.99, 3.91 and 2.53. The stability and protonation constants of InL (L = L1, L2)
      were also obtained from a combined potentiometry and UV-VIS spectrophotometry
      study. The reaction of InCl(3) with H(3)L1 and H(3)L2 led to the formation of the
      well-defined complexes InL1 and InL2, containing In(iii) ions coordinated by a
      seven (N(4),O(3)) donor atom set. These new complexes were fully characterized by
      spectroscopic methods (IR, NMR, ESI-MS), HPLC and by X-ray diffraction analysis
      in the case of InL1. The radioactive congener (111)InL2 was prepared from the
      reaction of (111)In-chloride with H(3)L2, in high yield and high radiochemical
      purity. (111)InL2 is a neutral complex that presents a hydrophilic character and
      exhibits a high in vitro and in vivo stability. H(3)L2 and InL2 do not inhibit
      the cell growth of A431 cervical carcinoma cells. In this EGFR-expressing cell
      line, (111)InL2 has shown very low cell internalization. These findings indicate
      that these DOTA-like chelators are not the best suited bifunctional ligands to
      obtain In(iii) complexes with adequate biological properties for targeting the
      EGFR-TK.

PMID- 21072344
TI  - The missing zinc: p53 misfolding and cancer.
AB  - The p53 tumor suppressor is a transcription factor that contains a single zinc
      ion near its DNA binding interface. Zn(2+) is required for site-specific DNA
      binding and proper transcriptional activation. In addition to its functional
      significance, zinc plays a dominant role in determining whether p53 folds
      productively or misfolds. Insufficient zinc and excess zinc cause p53 to misfold
      by distinct mechanisms which both result in functional loss. The zinc-binding
      status of p53 in the cell is impacted significantly by the presence of
      tumorigenic mutations and by metal ion homeostasis. This review discusses
      mechanisms by which zinc modulates folding and misfolding of p53, how improper
      metal binding and release leads to loss of function and cancer, and how
      misfolding can be rescued by metallochaperones.

PMID- 21072345
TI  - Remarkable effect of mobile phase buffer on the SEC-ICP-AES derived Cu, Fe and Zn
      metalloproteome pattern of rabbit blood plasma.
AB  - The development of an analytical method to quantify the major Cu, Fe and Zn
      containing metalloproteins in mammalian plasma has been recently reported. This
      method is based on the separation of plasma proteins by size exclusion
      chromatography (SEC) followed by the on-line detection of the metalloproteins by
      an inductively coupled plasma atomic emission spectrometer (ICP-AES). To assess
      whether the mobile phase buffer can affect the SEC-ICP-AES-derived
      metalloproteome pattern, thawed rabbit plasma was analyzed using phosphate
      buffered saline (PBS)-buffer (0.15 M, pH 7.4), Tris-buffer (0.1 and 0.05 M, pH
      7.4), Hepes-buffer (0.1 M, pH 7.4) or Mops-buffer (0.1 M, pH 7.4). In contrast to
      the Cu-specific chromatograms, the Fe and Zn-specific chromatograms that were
      obtained with Tris, Hepes and Mops-buffer were considerably different from those
      attained with PBS-buffer. The Tris, Hepes and Mops-buffer mediated redistribution
      of ~25% plasma Zn(2+) from <100 kDa to >100-600 kDa plasma proteins and to a
      smaller extent to a <10 kDa (Tris)(2)Zn(2+)-complex can be rationalized in terms
      of the abstraction of Zn(2+) from the weak binding site on albumin. In contrast,
      only Hepes and Mops-buffer redistributed ~20% of plasma Fe(3+) from the <100 kDa
      to the >600 kDa elution range. Based on these results and considering that the
      utilization of PBS-buffer has previously resulted in the detection of a number of
      Cu, Fe and Zn-containing metalloentities in rabbit plasma that was most
      consistent with literature data, this mobile phase buffer is recommended for
      metallomic studies regarding mammalian blood plasma.

PMID- 21072346
TI  - Free cadmium ions released from CdTe-based nanoparticles and their cytotoxicity
      on Phaeodactylum tricornutum.
AB  - The risk of nanoparticles (NPs) to organisms and the environment has become more
      noticeable alongside their rapid applications in many fields. The release of
      Cd(2+) from CdTe-based NPs (CdTe-NPs), an important class of engineered
      nanomaterials, is one of the possible factors responsible for the cytotoxicity of
      these NPs. Based on the same CdTe core, CdTe/CdS, CdTe/ZnS and CdTe/SiO(2) NPs
      were synthesized and their Cd(2+) release rates were carefully studied based on
      dialysis using inductively coupled plasma mass spectrometry (ICPMS). Results
      obtained indicated that the Cd(2+) release rates of the CdTe-NPs decreased in the
      order CdTe (8.78 ng mL(-1) mg(-1) h(-1)) > CdTe/CdS (2.63) > CdTe/SiO(2) (0.89) >
      CdTe/ZnS (0.72). Phaeodactylum tricornutum was used as a model diatom for
      evaluating the cytotoxicity of the CdTe-NPs. Results obtained from the CdTe-NPs
      exposure experiments together with ICPMS and fluorescence microscopy studies
      suggested that the cytotoxicity of the CdTe-NPs increased along with the increase
      in their Cd(2+) release rates. Effective coating materials such as ZnS and SiO(2)
      for the CdTe core significantly reduced the cytotoxicity of CdTe.

PMID- 21072347
TI  - Copper(I) and copper(II) binding to beta-amyloid 16 (Abeta16) studied by
      electrospray ionization mass spectrometry.
AB  - Copper-beta-amyloid 16 (Abeta16) complexes were investigated by electrospray
      ionization mass spectrometry (ESI-MS). Copper(i) and (ii) complexes were formed
      on-line in a microchip electrospray emitter by using a sacrificial copper
      electrode as the anode in positive ionization mode. In the presence of ascorbic
      acid in the peptide solution, the amount of Cu(i)-Abeta16 generated
      electrochemically was even higher. A kinetic model is proposed to account for the
      generation of copper complexes. The structure of Cu(i)-Abeta16 was investigated
      by tandem mass spectrometry (MS/MS), and the binding site of Cu(i) to Abeta16 was
      identified at the His13, His14 residues. Cu(ii)-Abeta16 was also investigated by
      MS/MS and, based on the unusual observations of a-ions, the two binding residues
      of His13 and His14 of Abeta16 to Cu(ii) were also confirmed. This approach
      provides direct information on Cu(i)-Abeta16 complexes generated in solution from
      metallic copper and gives evidence that both His13 and His14 are involved in the
      coordination of both Cu(i)- and Cu(ii)-Abeta16 complexes.

PMID- 21072348
TI  - Metal ions binding to NAD-glycohydrolase from the venom of Agkistrodon acutus:
      regulation of multicatalytic activity.
AB  - AA-NADase from Agkistrodon acutus venom is a unique multicatalytic enzyme with
      both NADase and AT(D)Pase activities. Among all identified NADases, only AA
      NADase contains Cu(2+) ions that are essential for its multicatalytic activity.
      In this study, the interactions between divalent metal ions and AA-NADase and the
      effects of metal ions on its structure and activity have been investigated by
      equilibrium dialysis, isothermal titration calorimetry, fluorescence, circular
      dichroism, dynamic light scattering and HPLC. The results show that AA-NADase has
      two classes of Cu(2+) binding sites, one activator site with high affinity and
      approximately six inhibitor sites with low affinity. Cu(2+) ions function as a
      switch for its NADase activity. In addition, AA-NADase has one Mn(2+) binding
      site, one Zn(2+) binding site, one strong and two weak Co(2+) binding sites, and
      two strong and six weak Ni(2+) binding sites. Metal ion binding affinities follow
      the trend Cu(2+) > Ni(2+) > Mn(2+) > Co(2+) > Zn(2+), which accounts for the
      existence of one Cu(2+) in the purified AA-NADase. Both NADase and ADPase
      activities of AA-NADase do not have an absolute requirement for Cu(2+), and all
      tested metal ions activate its NADase and ADPase activities and the activation
      capacity follows the trend Zn(2+) > Mn(2+) > Cu(2+) ~Co(2+) > Ni(2+). Metal ions
      serve as regulators for its multicatalytic activity. Although all tested metal
      ions have no obvious effects on the global structure of AA-NADase, Cu(2+)- and
      Zn(2+)-induced conformational changes around some Trp residues have been
      observed. Interestingly, each tested metal ion has a very similar activation of
      both NADase and ADPase activities, suggesting that the two different activities
      probably occur at the same site.

PMID- 21072349
TI  - Identification and characterization of gadolinium(III) complexes in biological
      tissue extracts.
AB  - The gadolinium species present in a rat kidney following intravenous
      administration of a gadolinium-based magnetic resonance contrast agent
      (OptimarkTM, Gadoversetamide injection) to a rat was examined in the present
      study. The major gadolinium species in the supernatant of the rat kidney tissue
      extracts was determined by reversed-phase liquid chromatography with online
      inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES). The
      identity of the compound was established by liquid chromatography electrospray
      ionization mass spectrometry (LC-ESI-MS) detection. The principal gadolinium(III)
      complex in a rat kidney tissue extract was identified as Gd-DTPA-BMEA 24 Hrs and
      7 days after a single intravenous injection of OptimarkTM (gadoversetamide; Gd
      DTPA-BMEA) at a dose of 5 mmol Gd/kg body weight. The study demonstrated for the
      first time the feasibility of the use of two complementary techniques, HPLC-ICP
      OES and HPLC-ESI-MS to study the in vivo behavior of gadolinium-based magnetic
      resonance contrast media.

PMID- 21072351
TI  - Copper handling machinery of the brain.
AB  - Copper plays an indispensable role in the physiology of the human central nervous
      system (CNS). As a cofactor of dopamine-beta-hydroxylase, peptidyl-alpha
      monooxygenase, superoxide dismutases, and many other enzymes, copper is a
      critical contributor to catecholamine biosynthesis, activation of neuropeptides
      and hormones, protection against reactive oxygen species, respiration and other
      processes essential for normal CNS function. Copper content in the CNS is tightly
      regulated, and changes in copper levels in the brain are associated with a wide
      spectrum of pathologies. However, the mechanistic understanding of copper
      transport in the CNS is still in its infancy. Little is known about copper
      distribution among various cell types or cell-specific regulation of copper
      homeostasis, despite the fact that the molecules mediating copper transport and
      distribution in the brain (CTR1, Atox1, CCS, ScoI/II, ATP7A and ATP7B) have been
      identified and their importance in CNS function increasingly understood. In this
      review, we summarize current knowledge about copper levels and uses in the CNS
      and describe the molecules involved in maintaining copper homeostasis in the
      brain.

PMID- 21072352
TI  - One is enough: insights into the two-metal ion nuclease mechanism from global
      analysis and computational studies.
AB  - The mechanistic details of metallonuclease reactions, typically supported by
      Mg(II), have a long and contentious history. Two-metal ion mechanisms have
      enjoyed much favor, based largely in the multitude of X-ray crystal structures of
      these enzymes with more than one metal ion per active site. Most recently, this
      mechanism has come under challenge. Reviewed herein are the applications of
      different experimental strategies that collectively support a mechanism in which
      only one metal ion is necessary for nucleic acid hydrolysis. Based on global
      kinetic analysis, analysis of reactions in which the nonsupportive Ca(ii) is
      added, and a number of computational approaches, secondary sites are proposed to
      either be occupied by activity-modulating metal ions or occupied in turn by a
      single metal that changes position during the course of the reaction.

PMID- 21072354
TI  - Metallomics study in CSF for putative biomarkers to predict cerebral vasospasm.
AB  - Cerebral vasospasm (CV) refers to physical narrowing of brain cerebral arteries
      due to over-contraction of the arterial wall, which often arises following a
      subarachnoid hemorrhage (SAH). CV is frequently associated with poorer outcomes
      in those patients. Between the ictus of SAH and its CV complication, there is a 3
      7 days delay, which provides a time window to predict and possibly prevent the
      onset CV. Since the precise pathomechanism of CV is still unclear and approaches
      for predicting it are inefficient, more effective ways of predicting CV need to
      be developed. As a protective nourishing fluid flows through the subarachnoid
      space, cerebrospinal fluid (CSF) closely relates to the health states of the
      central nervous system (CNS). Analysis of CSF can provide invaluable information
      to diagnose, treat and prevent diseases of the CNS because of its relatively
      direct representation of events in the brain. Therefore, we assume that the
      components in CSF and their alterations may reflect the state of aneurismal SAH
      and the development of vasospasm. In this study, three types of CSF from healthy
      control, and patients who suffered SAH and its complication, CV, were
      investigated via two-dimensional separations in combination with elemental and
      molecular mass spectrometry detection for the identification of elemental
      species. Size exclusion chromatography (SEC) was initially used with selective
      metal detection by inductively coupled plasma mass spectrometry (ICPMS) for
      characterizing size distribution of metal species. Various molecular distribution
      patterns were exhibited at different metal detection points (Fe, Ni, Cu, Zn and
      Pb). Further identification of possible metallopeptides and metalloprotein in
      tryptic digested fractions from the three sample types were made via reverse
      phase (RP)-Chip and electrospray mass spectrometry (MS) in combination with the
      Spectrum Mill data base search engine accessing appropriate data bases.
      Comparisons were generated to show suggested protein similarities or differences
      across the three CSF sample types. Six protein families with possible protein
      markers were further identified, and may be considered as possible focus areas
      for discovering valuable biomarkers to preclude the debilitating or deadly
      vasospasm.

PMID- 21072353
TI  - A study of the distribution of aluminium in human placental tissues based on
      alkaline solubilization with determination by electrothermal atomic absorption
      spectrometry.
AB  - Aluminium (Al) is a nonessential element known to induce neurotoxic effects, such
      as dialysis dementia, in patients on hemodialysis, with compromised kidney
      function. The role of Al in the progression of some neurodegenerative diseases,
      such as Alzheimer's disease (AD), is controversial, and remains unclear. The
      effects of Al on other vulnerable populations, such as fetuses and infants, have
      been infrequently studied. In the present study, Al has been measured in human
      placenta samples, comprising ~160 each of placenta bodies, placenta membranes,
      and umbilical cords, using electrothermal atomic absorption spectrometry (ETAAS)
      after atmospheric pressure digestion with tetramethylammonium hydroxide (TMAH)
      and ethylenediaminetetraacidic acid (EDTA). The sensitivity, or characteristic
      mass (m(0)), for Al at the 309.3-nm line was found to be 30 +/- 4 pg. The
      instrumental detection limit (IDL) (3s) for Al in solution was calculated as 0.72
      MUg L(-1) while the method detection limit (MDL) (3s) was 0.25 MUg g(-1).
      Accuracy was assessed through analysis of quality control (QC) materials,
      including certified reference materials (CRMs), in-house reference materials
      (RMs), and spike recovery experiments, of varying matrices. Placental tissue
      analyses revealed geometric mean concentrations of approximately 0.5 MUg g(-1) Al
      in placenta bodies (n = 165) and membranes (n = 155), while Al concentrations in
      umbilical cords (n = 154) were about 0.3 MUg g(-1). Al was detected in 95% of
      placenta bodies, and 81% of placenta membranes, but only in 46% of umbilical
      cords.

PMID- 21072355
TI  - Sample preparation strategies for quantitative analysis of catalase in red blood
      cells by elemental mass spectrometry.
AB  - A sample preparation strategy for the determination of the Fe-containing enzyme
      catalase (CAT) by Fe specific monitoring in human erythrocytes has been
      optimized. For this purpose, the combined use of elemental mass spectrometry (via
      inductively coupled plasma, ICP-MS), molecular mass spectrometry (via MALDI-TOF)
      and enzymatic activity measurements has been required. The procedure involved
      haemoglobin precipitation from cell lysate with a solution of ethanol-chloroform
      and preconcentration of the supernatant by using a Speed-Vac concentrator.
      Catalase recoveries of about 88 +/- 15% could be measured by monitoring the
      protein enzymatic activity before and after precipitation. Further fractionation
      of Fe-containing proteins from the preconcentrated extract was achieved by size
      exclusion chromatography (Superdex 200) with a mobile phase of ammonium acetate
      (0.05 M, pH 7.4) coupled to ICP-MS (Fe monitoring) and UV/VIS detection (specific
      absorption of the heme-group at 408 nm). A second dimensional chromatography of
      the CAT-positive activity fraction was carried out by anion-exchange
      chromatography (Mono Q 5/50) using for elution a linear gradient of ammonium
      acetate (0-0.750 M in 15 min). This second step revealed a single Fe-containing
      species in the chromatogram and permitted the unambiguous characterization of the
      CAT in such fractions by MALDI-TOF. Column recoveries were evaluated and were
      quantitative, in terms of Fe bound to protein and CAT activity.

PMID- 21072356
TI  - Using a dual-stable isotope tracer method to study the uptake, xylem transport
      and distribution of Fe and its chelating agent from stereoisomers of an Fe(III)
      chelate used as fertilizer in Fe-deficient Strategy I plants.
AB  - A dual-stable isotope tracer experiment was carried out with Fe-deficient sugar
      beet plants grown hydroponically and resupplied with differentially Fe labeled
      racemic and meso Fe(iii)-chelates of the ethylendiamine di(o-hydroxyphenylacetic)
      acid (o,oEDDHA). No short-term Fe isotope exchange reactions occurred in the
      nutrient solution and plants did not discriminate between (54)Fe and (57)Fe.
      After 3-6 h, stable Fe isotopes, chelating agents and chelates were analyzed in
      roots, xylem sap and leaves by ICP-MS and HPLC-ESI/TOFMS. Ferric chelate
      reductase rates, xylem transport and total uptake were 2-fold higher with the
      meso isomer than with the racemic one. Both chelating agent isomers were
      incorporated and distributed by plants at similar rates, in amounts one order of
      magnitude lower than those of Fe. After 6 h of Fe resupply, most of the Fe
      acquired was localized in roots, whereas most of the chelating agent was in
      leaves. In a separate experiment, Fe-deficient sugar beet and tomato plants were
      treated with different concentrations of Fe(iii)-o,oEDDHA (with a meso/racemic
      ratio of 1). The xylem sap Fe concentration at 24 h was unaffected by the chelate
      concentration, with xylem Fe(iii)-o,oEDDHA accounting for 1-18% of total Fe and
      xylem meso/racemic ratio close to 1. Although most of the Fe coming from Fe(iii)
      o,oEDDHA was taken up through a reductive dissociative mechanism, a small part of
      the Fe may be taken up via non-dissociative mechanisms.

PMID- 21072359
TI  - Metallomics approach for the identification of the iron transport protein
      transferrin in the blood of harbour seals (Phoca vitulina).
AB  - The health status of marine mammals such as harbour seals (Phoca vitulina)
      represents an indirect but powerful way for the assessment of environmental
      changes. The present work illustrates the first investigation and
      characterisation of Tf isolated from blood samples of North Sea harbour seals
      with a view to using changes in Tf isoform patterns as an additional parameter in
      extended studies of their health status. Therefore, an HPLC-ICP-MS approach has
      been developed which allows the highly resolved separation and fractionation of
      up to eight different Tf isoforms, as well as their sensitive and specific
      detection on the basis of their characteristic iron content. Molecule-specific
      detection techniques such as nanoLC-ESI-QTRAP-MS or MALDI-TOF-MS were used as
      complementary techniques to unambiguously identify the isolated proteins as Tf
      via cross species protein identification and to further characterise the
      molecular weight as well as the sialic acid content, which is responsible for the
      elution behaviour of the different isoforms during their ion exchange separation.
      A molecular mass above 80 kDa has been measured for the different seal Tf
      isoforms, which is in good agreement with the known molecular mass in other
      mammalian species, while the estimated pI of the different isoforms indicates
      some differences in comparison to other species. A number of homologies to known
      Tf sequences have been observed, which finally allows the cross species protein
      identification. The combined metallomics orientated analytical approach, which
      includes the complementary application of element and molecule-specific detection
      techniques, opens up interesting possibilities for the fast and targeted
      isolation and identification of a diagnostically relevant metal containing
      protein from an un-sequenced mammalian species prior to its utilisation in
      extended studies.

PMID- 21072358
TI  - Metallo-allixinate complexes with anti-diabetic and anti-metabolic syndrome
      activities.
AB  - Metabolic syndrome and the accompanied diabetes mellitus are both important
      diseases worldwide due to changes of lifestyle and eating habits. The number of
      patients with diabetes worldwide is estimated to increase to 300 million by 2025
      from 150-220 million in 2010. There are two main types of diabetes. In type 1
      diabetes, caused by destruction of pancreatic beta-cells resulting in absolute
      deficiency of intrinsic insulin secretion, the patients require exogenous insulin
      injections several times a day. In type 2 diabetes, characterized by insulin
      resistance and abnormal insulin secretion, the patients need exercise, diet
      control and/or several types of hypoglycemics. The idea of using metal ions for
      the treatment of diabetes originates from the report in 1899. The research on the
      role of metal ions that may contribute to the improvement of diabetes began. The
      orally active metal complexes containing vanadyl (oxidovanadium(iv)) ion and
      cysteine or other ligands were first proposed in 1990, and a wide class of
      vanadium, copper and zinc complexes was found to be effective for treating
      diabetes in experimental animals. We noticed a characteristic compound, allixin,
      which is a non-sulfur component in dry garlic. Its vanadyl and zinc complexes
      improved both types of diabetes following oral administration in diabetic
      animals. We then developed a new zinc complex with thioxoallixin-N-methyl (tanm),
      which is both a sulfur and N-methyl derivative of allixin, and found that this
      complex improves not only diabetes but also metabolic syndrome. Furthermore, new
      zinc complexes inspired from the zinc-tanm were prepared; one of them exceeded
      the activity of zinc-tanm. The mechanism of such complexes was studied in
      adipocytes. We describe here the usefulness of the development of metal-based
      complexes in the context of potential therapeutic application for diabetes and
      metabolic syndrome.

PMID- 21072360
TI  - Cytotoxic copper(II) salicylaldehyde semicarbazone complexes: mode of action and
      proteomic analysis.
AB  - The in vitro cytotoxic studies of a series of salicylaldehyde semicarbazones,
      HOC6H4CH=N-NHCONR2 (H2R2) and their Cu(II) complexes on a number of human tumor
      cell lines were conducted and it was observed that their cytotoxicities were
      enhanced following complexation to copper. These copper(II) complexes also
      demonstrated higher in vitro activities than the reference drug, cisplatin, on
      the tumor cell lines at micro molar range. Apoptotic assays and cell cycle
      analysis of the copper complexes, [Cu(HBnz2)Cl] and [Cu(HBu2)Cl] revealed that
      they mediated cytotoxicity in MOLT-4 cells via apoptosis. Further proteomic
      investigation of [Cu(HBnz2)Cl] and [Cu(HBu2)Cl] with respect to their protein
      expression profiles associated with their mode of action was conducted. By
      comparing the expression levels of 33 identified protein spots amongst the
      respective compound-treated profiles, we identified similarities in protein
      expression patterns between the two copper(II) complexes. The possible roles of
      the identified proteins in the execution of apoptosis by these copper(II)
      complexes are discussed.

PMID- 21072361
TI  - Zinc proteomes, phylogenetics and evolution.
AB  - Evolution has not been studied in detail with reference to the changing
      environment. This requires a study of the inorganic chemistry of organisms,
      especially metalloproteins. The evolution of organisms has been analysed many
      times previously using comparative studies, fossils, and molecular sequences of
      proteins, DNA and 16s rRNA (Zhang and Gladyshev, Chem. Rev., 2009, 109, 4828).
      These methods have led to the confirmation of Darwin's original proposal that
      evolution followed from natural selection in a changing environment often
      pictured as a tree. In all cases, the main tree in its upper later reaches has
      been well studied but its lower earlier parts are not so well defined. To
      approach this topic we have treated evolution as due to the intimate combination
      of the effect of chemical changes in the environment and in the organisms
      (Williams and da Silva, The Chemistry of Evolution, 2006, Elsevier). The best
      chemicals to examine are inorganic ions as they are common to both. As a more
      detailed example of the chemical study of organisms we report in this paper a
      bioinformatic approach to the characterization of the zinc proteomes. We deduce
      them from the 821 totally sequenced DNA of organisms available on NCBI,
      exploiting a published method developed by one of us (Andreini, Bertini and
      Rosato, Acc. Chem. Res., 2009, 42, 1471). Comparing the derived zinc-finger
      containing proteins and zinc hydrolytic enzymes in organisms of different
      complexity there is a correlation in their changes during evolution related to
      environmental change.

PMID- 21072362
TI  - Application of XANES spectroscopy in understanding the metabolism of selenium in
      isolated rainbow trout hepatocytes: insights into selenium toxicity.
AB  - Selenium (Se) is an essential element, but causes toxic effects in fish at a
      slightly elevated level beyond the threshold. However, the degree of Se toxicity
      differs depending on the chemical forms of Se (e.g., organic vs. inorganic) to
      which fish are exposed to. The mechanisms of Se metabolism and toxicity in fish,
      particularly at cellular level, are poorly understood. The present study was
      designed to examine the metabolic fate of different seleno-compounds, both
      inorganic and organic, in isolated hepatocytes of rainbow trout (Oncorhynchus
      mykiss) in primary culture using XANES spectroscopy. In cells exposed to 100 MUM
      of selenate and selenite for 6-24 h, elemental Se was found to be the primary
      metabolite. Whereas, selenocystine appeared to be the major metabolite in cells
      exposed to 100 MUM seleno-L-methionine for 6-24 h. Interestingly, we recorded L
      methionine-gamma-lyase activity in S9 fraction of cell lysate-an enzyme that
      directly catalyzes selenomethionine into methylselenol. We also found concurrent
      reduction of glutathione (GSH) concentration following reaction of seleno-L
      methionine with cellular S9 fraction. Moreover, we observed a rapid increase in
      cellular reactive oxygen species (ROS) generation with increasing seleno-L
      methionine exposure dose (100-1000 MUM). These findings indicated the rapid
      cellular metabolism of seleno-L-methionine into methylselenol at higher exposure
      dose (>=100 MUM), and the occurrence of GSH mediated redox cycling of
      methylselenol--a process that is known to produce reactive oxygen species (ROS).
      Overall, our results suggest that inorganic and organic selenium are metabolized
      through different metabolic pathways in rainbow trout hepatocytes. The findings
      of our study have important implications for understanding the chemical species
      specific differences in Se toxicity to fish.

PMID- 21072364
TI  - The hazards of iron loading.
AB  - Excessive or misplaced tissue iron now is recognized to pose a substantial health
      risk for an extensive array of endocrinological, gastrointestinal, infectious,
      neoplasmic, neurodegenerative, obstetric, ophthalmic, orthopedic, pulmonary and
      vascular diseases. Ingested, injected, inhaled and decompartmentalized iron
      contributes not only to disease, but also to aging and mortality. Iron is
      dangerous by catalyzing free radical formation and by serving as an essential
      nutrient for microbial and neoplasmic cell invaders. Our body cells exhibit wide
      variation in sensitivity to iron toxicity. Efficacy of our iron withholding
      defense system is modulated by numerous environmental, behavioral and genetic
      factors. A notable variety of methods for prevention and therapy of iron toxicity
      are now becoming available.

PMID- 21072365
TI  - Zinc release of Zn7-metallothionein-3 induces fibrillar type amyloid-beta
      aggregates.
AB  - The reactive oxygen species H2O2 promotes the Zn7-metallothionein-3 induced
      Abeta(40) aggregation of fibrillar type structures via slow cysteine oxidation
      and Zn(2+) release, whereas amorphous aggregates are formed by addition of Zn(2+)
      to Abeta(40).

PMID- 21072366
TI  - Three-dimensional elemental bio-imaging of Fe, Zn, Cu, Mn and P in a 6
      hydroxydopamine lesioned mouse brain.
AB  - Three dimensional maps of iron (Fe), zinc (Zn), copper (Cu), manganese (Mn) and
      phosphorous (P) in a 6-hydroxydopamine (6-OHDA) lesioned mouse brain were
      constructed employing a novel quantitative laser ablation-inductively coupled
      plasma-mass spectrometry (LA-ICP-MS) imaging method known as elemental bio
      imaging. The 3D maps were produced by ablating serial consecutive sections taken
      from the same animal. Each section was quantified against tissue standards
      resulting in a three dimensional map that represents the variation of trace
      element concentrations of the mouse brain in the area surrounding the substantia
      nigra (SN). Damage caused by the needle or the toxin did not alter the
      distribution of Zn, and Cu but significantly altered Fe in and around the SN and
      both Mn and Fe around the needle track. A 20% increase in nigral Fe concentration
      was observed within the lesioned hemisphere. This technique clearly shows the
      natural heterogeneous distributions of these elements throughout the brain and
      the perturbations that occur following trauma or intoxication. The method may
      applied to three-dimensional modelling of trace elements in a wide range of
      tissue samples.

PMID- 21072367
TI  - Enhanced photodynamic effect of cobalt(III) dipyridophenazine complex on
      thyrotropin receptor expressing HEK293 cells.
AB  - Ternary cobalt(III) complexes [CoL(B)] (1-3) of a trianionic tetradentate
      phenolate-based ligand (L) and phenanthroline bases (B), viz. 1,10-phenanthroline
      (phen in 1), dipyridoquinoxaline (dpq in 2) and dipyridophenazine (dppz in 3) are
      synthesized, characterized from X-ray crystallographic, analytical and spectral
      techniques, and their utility in photodynamic therapy (PDT) of thyroid diseases
      caused by TSH receptor dysfunction is probed. The complexes display a visible
      spectral band within the PDT spectral window at ~690 nm. Photodynamic potential
      was estimated through DNA cleavage activity of the dpq and dppz complexes in UV-A
      light of 365 nm and red light of 676 nm. The reactions proceed via the hydroxyl
      radical pathway. The complexes retain their DNA photocleavage activity in red
      light under anaerobic conditions, a situation normally prevails in hypoxic tumor
      core. Investigation into the photocytotoxic potential of these complexes showed
      that the dppz complex 3 is approximately 4-fold more active in the HEK293 cells
      expressing human thyrotropin receptor (HEK293-hTSHR) than in the parental cell
      line and has an insignificant effect on an unrelated human cervical carcinoma
      cell line (HeLa). Photoexcitation of complex 3 in HEK293-hTSHR cells leads to
      damage hTSHR as evidenced from the decrease in cAMP formation both in absence and
      presence of hTSH and decrease in the TSHR immunofluorescence with a concomitant
      cytoplasmic translocation of the membrane protein, cadherin. The involvement of
      hTSHR is evidenced from the ability of complex 3 to bind to the extracellular
      domain of hTSHR (hTSHR-ECD) with a K(d) value of 81 nM and from the photocleavage
      of hTSHR-ECD.

PMID- 21072368
TI  - Effects of large-scale amino acid substitution in the polypeptide tether
      connecting the heme and molybdenum domains on catalysis in human sulfite oxidase.
AB  - Sulfite oxidase (SO) is a molybdenum-cofactor-dependent enzyme that catalyzes the
      oxidation of sulfite to sulfate, the final step in the catabolism of the sulfur
      containing amino acids, cysteine and methionine. The catalytic mechanism of
      vertebrate SO involves intramolecular electron transfer (IET) from molybdenum to
      the integral b-type heme of SO and then to exogenous cytochrome c. However, the
      crystal structure of chicken sulfite oxidase (CSO) has shown that there is a 32 A
      distance between the Fe and Mo atoms of the respective heme and molybdenum
      domains, which are connected by a flexible polypeptide tether. This distance is
      too long to be consistent with the measured IET rates. Previous studies have
      shown that IET is viscosity dependent (Feng et al., Biochemistry, 2002, 41, 5816)
      and also dependent upon the flexibility and length of the tether (Johnson-Winters
      et al., Biochemistry, 2010, 49, 1290). Since IET in CSO is more rapid than in
      human sulfite oxidase (HSO) (Feng et al., Biochemistry, 2003, 42, 12235) the
      tether sequence of HSO has been mutated into that of CSO, and the resultant
      chimeric HSO enzyme investigated by laser flash photolysis and steady-state
      kinetics in order to study the specificity of the tether sequence of SO on the
      kinetic properties. Surprisingly, the IET kinetics of the chimeric HSO protein
      with the CSO tether sequence are slower than wildtype HSO. This observation
      raises the possibility that the composition of the non-conserved tether sequence
      of animal SOs may be optimized for individual species.

PMID- 21072370
TI  - Metallomics, a growing success!

PMID- 21072372
TI  - Analytical methodologies for metallomics studies of antitumor Pt-containing
      drugs.
AB  - Pt-containing drugs are nowadays essential components in cancer chemotherapy.
      However, drug resistance and side effects limit the efficiency of the treatments.
      In order to improve the response to Pt-based drugs, different administration
      strategies or new Pt-compounds have been developed with little success. The
      reason for this failure could be that the mechanism of action of these drugs is
      not completely understood. In this way, metallomics studies may contribute to
      clarify the interactions of Pt-containing drugs within the organism. This review
      is mainly focused on the role of Analytical Chemistry on the study of the
      interactions between Pt-based drugs and biomolecules. A summary of the analytical
      techniques and the most common sample treatment procedures currently used in
      metallomics studies of these drugs is presented. Both are of paramount importance
      to study these complex samples preserving the drug-biomolecule interaction.
      Separation and detection techniques must be carefully selected in order to
      achieve the intended goals. The use of multidimensional hyphenated techniques is
      usually necessary for a better understanding of the Pt-based drugs interactions
      in the organism. An overview of Pt-drugs biological interactions is presented,
      considering the different sample matrices and the drugs course through the
      organism. Samples analysed in the included studies are blood, urine, cell
      cytosol, DNA as well as the drugs themselves and their derivatives. However, most
      of these works are based on in vitro experiments or incubations of standards,
      leading in some cases to contradictory results depending on the experimental
      conditions used. Though in vivo experiments represent a great challenge due to
      the high complexity and the low concentrations of the Pt-adducts in real samples,
      these studies must be undertaken to get a deeper understanding of the real
      interactions concerning Pt-containing drugs.

PMID- 21072373
TI  - Bioinformatics in bioinorganic chemistry.
AB  - Bioinformatics is a central discipline in modern life sciences aimed at
      describing the complex properties of living organisms starting from large-scale
      data sets of cellular constituents such as genes and proteins. In order for this
      wealth of information to provide useful biological knowledge, databases and
      software tools for data collection, analysis and interpretation need to be
      developed. In this paper, we review recent advances in the design and
      implementation of bioinformatics resources devoted to the study of metals in
      biological systems, a research field traditionally at the heart of bioinorganic
      chemistry. We show how metalloproteomes can be extracted from genome sequences,
      how structural properties can be related to function, how databases can be
      implemented, and how hints on interactions can be obtained from bioinformatics.

PMID- 21072374
TI  - Parallel on-line detection of a methylbismuth species by hyphenated GC/EI-MS/ICP
      MS technique as evidence for bismuth methylation by human hepatic cells.
AB  - Methylation of metal(loid)s by bacteria or even mammals is a well known process
      that can lead to increased toxicity for humans. Nevertheless, reliable analytical
      techniques and tools are indispensable in speciation analysis of trace elements,
      especially since environmental or biological samples are usually characterised by
      complex matrices. Here the methylating capability of hepatic cells was observed
      in vitro. HepG2 cells were incubated with colloidal bismuth subcitrate, bismuth
      cysteine and bismuth glutathione, respectively for a period of 24 h. For
      identification the cell lysate was ethylated by sodium tetraethyl borate under
      neutral conditions. After cryo focussing by purge and trap, the bismuth
      speciation was carried out via GC/EI-MS/ICP-MS. Colloidal bismuth subcitrate and
      bismuth cysteine were methylated by HepG2 cells, while no methylated bismuth
      species was detected after incubation with bismuth glutathione.

PMID- 21072375
TI  - Nicotianamine forms complexes with Zn(II) in vivo.
AB  - The non-proteinogenic amino acid nicotianamine (NA) is a major player in plant
      metal homeostasis. It is known to form complexes with different transition metals
      in vitro. Available evidence associates NA with translocation of Fe, and possibly
      other micronutrients, to and between different plant cells and tissues. To date,
      however, it is still extremely challenging to detect metal-ligand complexes in
      vivo because tissue disruption immediately changes the chemical environment and
      thereby the availability of binding partners. In order to overcome this
      limitation we used various Schizosaccharomyces pombe strains expressing a plant
      NAS gene to study formation of metal-NA complexes in vivo. Tolerance,
      accumulation and competition data clearly indicated formation of Zn(ii)-NA but
      not of Cu(ii)-NA complexes. Zn(ii)-NA was then identified by X-ray absorption
      spectroscopy (XAS). About half of the cellular Zn was found to be bound by NA in
      NAS-expressing cells while no NA-like ligands were detected by XAS in control
      cells not expressing NAS. Given the high conservation of eukaryotic metal
      homeostasis components, these results strongly suggest the possible existence of
      Zn(ii)-NA complexes also in planta. Reported observations implicating NA in plant
      Zn homeostasis would then indeed be attributable to direct interaction of Zn(ii)
      with NA rather than only indirectly to perturbations in Fe metabolism. Re
      evaluation of extended X-ray absorption fine structure (EXAFS) spectra for the Zn
      hyperaccumulator Thlaspi caerulescens showed that NA is as expected not a major
      storage ligand for Zn. Instead it is hypothesized to be involved in efficient
      translocation of Zn to above-ground tissues in hyperaccumulators.

PMID- 21072376
TI  - Inhibitory effect of CuSO4 on alpha-glucosidase activity in ddY mice.
AB  - We investigated the effects of divalent alkaline earth and first-row transition
      metal and zinc ions on alpha-glucosidase activity in vitro and in vivo. CuSO4 and
      ZnSO4 exhibited a high alpha-glucosidase inhibitory effect in vitro. The IC(50)
      values of CuSO4 were 0.77 +/- 0.01 (substrate; maltose) and 0.78 +/- 0.01
      (substrate; sucrose), and those of ZnSO4 were 5.49 +/- 0.14 (substrate; maltose)
      and 4.70 +/- 0.06 (substrate; sucrose) for yeast alpha-glucosidase. On the basis
      of Lineweaver-Burk plots, both CuSO4 and ZnSO4 exhibited different modes of
      inhibition against alpha-glucosidase. Subsequently, oral glucose and sucrose
      tolerance tests (OGTT and OSTT) were performed on non-diabetic ddY mice to
      examine the effect of the metal ions on their blood glucose levels. As a result
      of single oral administration of CuSO4 in non-diabetic ddY mice, a significant
      and potent lowering of the blood glycemic response toward disaccharide, sucrose,
      ingestion was observed at 45 min after doses of 0.08 and 0.24 mmol kg(-1) body
      weight. In contrast, the CuSO4 administration showed no suppression of the
      elevation of blood glucose levels in mice after a monosaccharide, glucose,
      administration. These results indicate that CuSO4 suppresses disaccharide
      digestion by inhibiting alpha-glucosidase activity in the epithelium of the small
      intestine, suggesting that antidiabetic Cu complexes with some ligands have a
      similar action mechanism to that of alpha-glucosidase inhibitor, acarbose,
      currently used for clinical purposes.

PMID- 21072377
TI  - Coordination of platinum therapeutic agents to met-rich motifs of human copper
      transport protein1.
AB  - Platinum therapeutic agents are widely used in the treatment of several forms of
      cancer. Various mechanisms for the transport of the drugs have been proposed
      including passive diffusion across the cellular membrane and active transport via
      proteins. The copper transport protein Ctr1 is responsible for high affinity
      copper uptake but has also been implicated in the transport of cisplatin into
      cells. Human hCtr1 contains two methionine-rich Mets motifs on its extracellular
      N-terminus that are potential platinum-binding sites: the first one encompasses
      residues 7-14 with amino acid sequence Met-Gly-Met-Ser-Tyr-Met-Asp-Ser and the
      second one spans residues 39-46 with sequence Met-Met-Met-Met-Pro-Met-Thr-Phe. In
      these studies, we use liquid chromatography and mass spectrometry to compare the
      binding interactions between cisplatin, carboplatin and oxaliplatin with
      synthetic peptides corresponding to hCtr1 Mets motifs. The interactions of
      cisplatin and carboplatin with Met-rich motifs that contain three or more
      methionines result in removal of the carrier ligands of both platinum complexes.
      In contrast, oxaliplatin retains its cyclohexyldiamine ligand upon platinum
      coordination to the peptide.

PMID- 21072378
TI  - Functional metal ions in nucleic acids.
AB  - Metal ions are inevitably involved in almost every aspect of nucleic acid
      chemistry. Their most prominent role is certainly the maintenance of nucleic acid
      structural integrity. However, they serve various other roles as well, e.g. as
      catalytic co-factors in ribozymes, in determining the secondary structure of
      tetra-stranded helices, during RNA folding, and possibly even in enabling
      nucleobase-centred acid/base catalysis under physiological conditions and in
      modulating homogeneous genetic recombination. This tutorial review gives a
      compact overview of the multifaceted situations in which metal ions exert
      specific functions in nucleic acids, also including a discussion of structural
      metal ions in regular DNA and RNA as well as triple helices, guanine
      quadruplexes, and helical junctions. It has a strong focus on metal ions that are
      naturally present in living systems and only occasionally includes a description
      of the interaction of exogenous metal complexes with nucleic acids (or their
      components), provided that the results of these studies can be transferred into
      the context of endogenous metal ions.

PMID- 21072379
TI  - R161, K452 and R460 residues are vital for metal-citrate complex transport in
      Cit(Sc) from Streptomyces coelicolor.
AB  - Recent discoveries have been made that demonstrate Gram-positive bacteria can
      transport metal-citrate complexes through the CitMHS family of proteins in
      symport with H(+) ions. The CitMHS family of transporters investigated to date
      have the ability to selectively transport only certain metal-citrate complexes.
      Despite sharing amino acid sequence similarity as high as 73%; predicting what
      complexes are transported remains difficult. The iron-citrate transporter from
      Streptomyces coelicolor has been mutated at three postulated critical sites
      (R161, K452 and R460) based on activity modeling against the LacY permease. All
      three mutants eliminate or greatly reduce uptake of metal-citrate complexes
      tested. The implications of this are discussed.

PMID- 21072382
TI  - Cysteine proteases as targets for metal-based drugs.
AB  - The discovery of the platinum anticancer drug cisplatin provided a major stimulus
      for research into metal-based drugs. The molecular target for the platinum agents
      is DNA; however recent developments in inorganic medicinal chemistry have
      identified several alternative novel targets for metal-based drugs. Biological
      molecules with essential thiol groups are attractive targets. Thiol-containing
      molecular targets include the redox enzymes thioredoxin reductase and glutathione
      reductase, transcription factors, and cysteine proteases such as caspases and
      cathepsins. Inorganic chemistry offers many opportunities for medicinal
      chemistry, and alternative targets for metal-based drugs are reviewed, with a
      focus on cysteine proteases. The cathepsin cysteine proteases have numerous
      physiological functions, and have been implicated in diseases including cancer,
      autoimmune and inflammatory, and parasitic diseases. The catalytic mechanism of
      these enzymes is dependent upon a cysteine at the active site. We postulate that
      metal complexes can inhibit these enzymes via a ligand substitution with the
      thiol of the active site cysteine. We have investigated several classes of metal
      complexes including cyclometalated organo gold(iii) and Pd(ii) complexes, and a
      series of rhenium(v) mixed ligand oxorhenium complexes as inhibitors of cathepsin
      cysteine proteases. Mechanistic studies were conducted on the latter supporting
      the hypothesis of active site-directed inhibition. These data are reviewed below
      and discussed in the context of possible therapeutic applications including
      cancer and parasitic disease.

PMID- 21072380
TI  - Bioimaging of copper alterations in the aging mouse brain by autoradiography,
      laser ablation inductively coupled plasma mass spectrometry and
      immunohistochemistry.
AB  - Copper may play an important role in the brain in aging and neurodegenerative
      diseases. We compare the active Cu uptake, Cu-containing enzyme levels, and total
      Cu distribution in the brains of young and aging mice. (67)Cu was administered
      intravenously to 2, 7-9, and 14 month old mice. Active uptake of (67)Cu in the
      brain was measured at 24 h by digital phosphor autoradiography. Cerebral
      superoxide dismutase-1 (SOD-1) and cytochrome-C oxidase subunit-1 (CCO-1) levels
      were analyzed by immunohistochemistry. The total Cu distribution in brain section
      was determined by imaging laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS). In aging mice, active (67)Cu uptake and SOD-1 levels
      were significantly decreased in the brain, whereas blood (67)Cu and CCO-1 levels
      were similar for all mice, irrespective of age. Paradoxically, global Cu cerebral
      content was increased in aged mice, suggesting that regulation of active Cu
      uptake by the brain may be linked to total Cu levels in an attempt to maintain Cu
      homeostasis. However, focal areas of both decreased Cu uptake and Cu content were
      noted in the striatum and ventral cortex in aging mice. These focal areas of Cu
      deficit correspond to the regions of greatest reduction in SOD-1 in the aged
      mice. In aging, dysregulated Cu homeostasis may result in decreased SOD-1 levels,
      which may contribute to oxidative vulnerability of the aging brain. This study
      illustrates the importance of a multi-modality approach in studying the
      biodistribution and homeostasis of Cu in the brain.

PMID- 21072383
TI  - Metalloproteomics and metal toxicology of alpha-synuclein.
AB  - Significant evidence has been accumulated linking exposure to heavy metals and/or
      distortion of metal homeostasis with the development of various neurodegenerative
      diseases. alpha-Synuclein is known to be involved in pathogenesis of a subset of
      neurodegenerative diseases collectively known as synucleinopathies. Therefore the
      interplay between metals, alpha-synuclein and neurodegeneration has attracted
      significant attention of researchers. This review discusses some of the aspects
      of the alpha-synuclein metalloproteomics and represents the peculiarities and
      consequences of alpha-synuclein interaction with various metal ions. Both non
      specific and specific binding of this protein to metals is considered together
      with the analysis of the effects of such interactions on alpha-synuclein
      structure and aggregation propensity.

PMID- 21072384
TI  - Selective mitochondrial accumulation of cytotoxic dinuclear polypyridyl
      ruthenium(II) complexes.
AB  - The lipophilic ligand-bridged dinuclear cation Rubb16 is significantly cytotoxic
      and preferentially accumulates in the mitochondria of the L1210 murine leukemia
      cancer cell line.

PMID- 21072385
TI  - 2-Oxoglutarate oxygenases are inhibited by a range of transition metals.
AB  - 2-Oxoglutarate oxygenases are inhibited by a range of transition metals, as
      exemplified by studies on human histone demethylases and prolyl hydroxylase
      domain 2 (PHD2 or EGLN1). The biological effects associated with 2-oxoglutarate
      oxygenase inhibition may result from inhibition of more than one enzyme and by
      mechanisms in addition to simple competition with the Fe(ii) cofactor.

PMID- 21072386
TI  - Formation and study of single metal ion-phospholipid complexes in biphasic
      electrospray ionization mass spectrometry.
AB  - Single metal ion-phospholipid complexes are observed in biphasic electrospray
      ionization mass spectrometry (BESI-MS) using a dual-channel microsprayer. Such a
      microsprayer makes it possible to put into contact two immiscible liquids within
      the Taylor cone. Thus, L-alpha-dipalmitoyl phosphatidylcholine (DPPC) dissolved
      in 1,2-dichloroethane (DCE) reacts with aqueous metal cations (M = Na(+), K(+),
      Ca(2+), Cu(2+), La(3+)) yielding the formation of [M-DPPC(n)](z+) complexes. The
      number of phospholipid molecules ranges from 1 to 4 for monovalent ions, to 8 for
      divalent and to more than 10 for trivalent ions respectively. The large number of
      ligands observed involves the formation of solvent free single ion-phospholipid
      complexes.

PMID- 21072387
TI  - Iron-binding and mobilization from ferritin by polypyridyl ligands.
AB  - Polypyridyl ligands were investigated for their ability to bind and mobilize
      iron(ii) from ferritin in aqueous solution. Association constants with iron(ii)
      (pFe(II)) were determined for the pentadentate ligands N4Py (pFe(II) = 14.4) and
      Bn-TPEN (pFe(II) = 13.7) using a competition method with the hexadentate ligand
      TPEN (pFe(II) = 14.6, 0.1 M KNO(3)). Ferrous complexes were formed using the
      polypyridyl ligands and ferritin as the sole iron source in the presence of
      reductant. The observed rates of iron mobilization from ferritin were dependent
      on reductant and were higher in the presence of ascorbate than dithiothreitol.
      TPEN, N4Py and Bn-TPEN demonstrated comparable and in some cases faster rates and
      higher levels of iron mobilization when compared to the iron(ii) chelator 1,10
      phenanthroline, particularly at low concentrations of chelator.

PMID- 21072388
TI  - Comparison of selenohomolanthionine and selenomethionine in terms of selenium
      distribution and toxicity in rats by bolus administration.
AB  - The distribution and metabolism of selenohomolanthionine (4,4'-selenobis[2
      aminobutanoic acid], SeHLan), a newly identified selenoamino acid in selenized
      Japanese pungent radish, were compared with those of selenomethionine (SeMet) in
      rats. Either selenoamino acid was injected intravenously at a bolus dose of 1.0
      mg Se/kg body weight. SeMet was preferably accumulated in the pancreas,
      increasing the serum amylase level, an index of pancreatic damage. SeHLan was
      preferably accumulated in the kidneys, raising the serum creatinine level, an
      index of kidney damage. On the other hand, the levels of two major urinary
      selenometabolites, i.e., Se-methylseleno-N-acetyl-galactosamine and
      trimethylselenonium, were comparable between SeHLan- and SeMet-administered rats,
      suggesting that there may be no differences in the efficiency of metabolism of
      these two selenoamino acids to the urinary selenometabolites despite the
      difference in distribution. SeHLan is expected to be a potential supplemental
      source of Se without inducing the onset of pancreatic damage. The specific
      toxicity of SeHLan to the kidneys may be avoided if its dose is lower than the
      one used in the present study.

PMID- 21072389
TI  - Synthesis and biological applications of ionic triphenyltin(IV) chloride
      carboxylate complexes with exceptionally high cytotoxicity.
AB  - The reaction of N-phthaloylglycine (P-GlyH), N-phthaloyl-l-alanine (P-AlaH), and
      1,2,4-benzenetricarboxylic 1,2-anhydride (BTCH) with triethylamine led to the
      formation of the corresponding ammonium salts [NHEt(3)][P-Gly] (1), [NHEt(3)][P
      Ala] (2) and [NHEt(3)][BTC] (3) in very high yields. The subsequent reaction of 1
      3 with triphenyltin(iv) chloride (1 : 1) yielded the compounds
      [NHEt(3)][SnPh(3)Cl(P-Gly)] (4), [NHEt(3)][SnPh(3)Cl(P-Ala)] (5), and
      [NHEt(3)][SnPh(3)Cl(BTC)] (6), respectively. The molecular structure of 4 was
      determined by X-ray diffraction studies. The cytotoxic activity of the ammonium
      salts (1-3) and the triphenyltin(iv) chloride derivatives (4-6) were tested
      against human tumor cell lines from five different histogenic origins: 8505C
      (anaplastic thyroid cancer), A253 (head and neck cancer), A549 (lung carcinoma),
      A2780 (ovarian cancer) and DLD-1 (colon cancer). Triphenyltin(iv) chloride
      derivatives (4-6) show very high activity against these cell lines while the
      ammonium salts of the corresponding carboxylic acids (1-3) are totally inactive.
      The most active compound is 4 which is 50 times more active than cisplatin.
      Compound 4 is found to induce apoptosis via extrinsic pathways on DLD-1 cell
      lines, probably by accumulation of caspases 2, 3 and 8. Furthermore, compound 4
      seems to cause disturbances in G1 and G2/M phases in cell cycle of DLD-1 cell
      line.

PMID- 21072390
TI  - A fast and sensitive assay for measuring the activity and enantioselectivity of
      transaminases.
AB  - A fast and sensitive method for screening transaminase activity and
      enantioselectivity, using D- and L-amino acid oxidases, allows new amine
      substrates to be rapidly identified.

PMID- 21072391
TI  - Dynamics of photogenerated holes in nanocrystalline alpha-Fe2O3 electrodes for
      water oxidation probed by transient absorption spectroscopy.
AB  - Transient absorption spectroscopy on the MUs-s time scale is used to monitor the
      yield and decay dynamics of photogenerated holes in nanocrystalline hematite
      photoanodes. In the absence of a positive applied bias, these holes are observed
      to undergo rapid electron-hole recombination. The application of a positive bias
      results in the generation of long-lived (3 +/- 1 s lifetime) photoholes.

PMID- 21072392
TI  - Rapid and reversible formation of a crystalline hydrate of a metal-organic
      framework containing a tube of hydrogen-bonded water.
AB  - The flexible metal-organic framework MIL-53(Cr) undergoes a dramatic volume
      expansion upon immersion in water at room temperature to form a crystalline
      hydrate in which water is held as a hydrogen-bonded tube: the hydration is
      readily reversible under ambient conditions as shown by time-resolved powder X
      ray diffraction.

PMID- 21072393
TI  - Ferroelectric mobile water.
AB  - In molecular dynamics simulations single-domain ferroelectric water is produced
      under ordinary ambient conditions utilizing carbon nanotubes open to a water
      reservoir. This ferroelectric water diffuses while keeping its proton-ordered
      network intact. The mobile/immobile water transitions and the step-wise changes
      in net polarization of water are observed to occur spontaneously. The immobile
      water becomes mobile by transforming into the single-domain ferroelectric water.
      Our general notion of relating a more highly ordered structure with a lower
      temperature has so far restricted researchers' attention to very low temperatures
      when experimenting on proton-ordered phases of water. The present study improves
      our general understanding of water, considering that the term 'ferroelectric
      water' has so far practically stood for 'ferroelectric ice,' and that single
      domain ferroelectric water has not been reported even for the ice nanotubes.

PMID- 21072394
TI  - Stepwise assembly of two 3d-4d heterometallic coordination polymers based on a
      hexanuclear silver(I) metalloligand.
AB  - Two novel 3d-4d heterometallic coordination polymers
      {[Cu(3)(bipy)(3)(H(2)O)(5)][Ag(6)(mna)(6)].11.5H(2)O}(n) (1) and
      {[Zn(3)(eda)(3)(H(2)O)(4)][Ag(6)(mna)(6)].8H(2)O}(n) (2) were synthesized based
      on a hexanuclear silver(I) metalloligand by a three-step synthetic method (bipy =
      2, 2'-bipyridine, eda = ethylenediamine and H(2)mna = 2-mercaptonicotinic acid).
      The photoluminescence behaviors of 1 and 2 were also discussed.

PMID- 21072395
TI  - Iron-catalyzed synthesis of polysubstituted pyrroles via [4C+1N] cyclization of 4
      acetylenic ketones with primary amines.
AB  - A highly efficient iron-catalyzed approach to polysubstituted pyrroles has been
      developed through the [4C+1N] cyclization of 4-acetylenic ketones with primary
      amines, leading to the synthesis of a variety of tetra- and fully-substituted
      pyrroles as well as fused pyrrole derivatives in good to excellent yields.

PMID- 21072396
TI  - Replication NAND gate with light as input and output.
AB  - Logic operations can highlight information transfer within complex molecular
      networks. We describe here the design of a peptide-based replication system that
      can be detected by following its fluorescence quenching. This process is used to
      negate the signal of light-activated replication, and thus to prepare the first
      replication NAND gate.

PMID- 21072397
TI  - Unsymmetrical diimine complexes of iron(II) and manganese(II): synthesis,
      structure and photoluminescence of an isomer.
AB  - Two bis(unsymmetrical diimine) complexes of
      (L(NO(2))(phi1))(L(NO(2))(phi2))M(II)Cl(2) family with M = Fe and Mn, are
      reported (L(NO(2))(phi) = (E)-3-nitro-N-(pyridine-2-ylmethylene)aniline; phi =
      dihedral angle between the diimine unit including pyridine ring and the phenyl
      ring planes). Pure tcc-(L(NO2)(33.6))(L(NO2)(79.3))Fe(II)Cl(2).0.5H(2)O (1) and
      tcc-(L(NO2)(32.0))(L(NO2)(79.4))Mn(II)Cl(2).0.5H(2)O (2) isomers have been
      successfully isolated in high yields and characterized by elemental analyses,
      variable temperature magnetic susceptibility measurements, IR, mass, UV-vis and
      Mossbauer spectra including the single-crystal X-ray structure determinations
      that identified strong intermolecular non-bonding interactions in lattice (tcc
      refers to trans-cis-cis positions with respect to pyridine N-imine N-Cl donors).
      Geometries optimizations of all possible tcc, ttt, ctc, ccc and cct isomers of
      iron at the B3LYP/DFT level in gas-phase have shown that the tcc-isomer
      incorporating two non-equivalent ligands as in
      (L(NO(2))(42))(L(NO(2))(61))Fe(II)Cl(2), 1 (g), is stabilized by 6-20 kJ mol(-1)
      compared to other isomers where two ligands are equivalent. The frozen methanol
      glasses of 1 and 2 are luminescent at 77 K (1: lambda(ext) = 370, lambda(em) =
      521 nm, chi(2) = 1.3, tau(avg) = 0.57 ns; 2: lambda(ext) = 368, lambda(em) = 524
      nm, chi(2) = 1.1, tau(avg) = 0.90 ns). The DFT calculations have identified four
      closely spaced localized pi(*) orbitals comprising of two non-equivalent ligands
      as UPMOs. The features contrast the tcc-isomer of (L(phi))(2)Fe(II)Cl(2) (3),
      congener of 1 without -NO(2) substitution and non-emissive (bpy)(2)Fe(II)Cl(2)
      (4) where two ligands are equivalent. TD-DFT calculations have assigned intra
      ligand (IL) and ligand to ligand charge transfer (LLCT) dominated excited states
      as the origin of luminescence of 1 and 2.

PMID- 21072398
TI  - Electrostatic interactions between diffuse soft multi-layered (bio)particles:
      beyond Debye-Huckel approximation and Deryagin formulation.
AB  - We report a steady-state theory for the evaluation of electrostatic interactions
      between identical or dissimilar spherical soft multi-layered (bio)particles, e.g.
      microgels or microorganisms. These generally consist of a rigid core surrounded
      by concentric ion-permeable layers that may differ in thickness, soft material
      density, chemical composition and degree of dissociation for the ionogenic
      groups. The formalism allows the account of diffuse interphases where
      distributions of ionogenic groups from one layer to the other are position
      dependent. The model is valid for any number of ion-permeable layers around the
      core of the interacting soft particles and covers all limiting situations in
      terms of nature of interacting particles, i.e. homo- and hetero-interactions
      between hard, soft or entirely porous colloids. The theory is based on a rigorous
      numerical solution of the non-linearized Poisson-Boltzmann equation including
      radial and angular distortions of the electric field distribution within and
      outside the interacting soft particles in approach. The Gibbs energy of
      electrostatic interaction is obtained from a general expression derived following
      the method by Verwey and Overbeek based on appropriate electric double layer
      charging mechanisms. Original analytical solutions are provided here for cases
      where interaction takes place between soft multi-layered particles whose size and
      charge density are in line with Deryagin treatment and Debye-Huckel
      approximation. These situations include interactions between hard and soft
      particles, hard plate and soft particle or soft plate and soft particle. The
      flexibility of the formalism is highlighted by the discussion of few situations
      which clearly illustrate that electrostatic interaction between multi-layered
      particles may be partly or predominantly governed by potential distribution
      within the most internal layers. A major consequence is that both amplitude and
      sign of Gibbs electrostatic interaction energy may dramatically change depending
      on the interplay between characteristic Debye length, thickness of ion-permeable
      layers and their respective protolytic features (e.g. location, magnitude and
      sign of charge density). This formalism extends a recent model by Ohshima which
      is strictly limited to interaction between soft mono-shell particles within
      Deryagin and Debye-Huckel approximations under conditions where ionizable sites
      are completely dissociated.

PMID- 21072399
TI  - Magnetic self-assembly of gold nanoparticle chains using dipolar core-shell
      colloids.
AB  - The preparation of gold nanoparticle (AuNP) assemblies was conducted by the
      synthesis and dipolar assembly of ferromagnetic core-shell nanoparticles composed
      of AuNP cores and cobalt NP shells. Dissolution of metallic Co phases with
      mineral acids afforded self-assembled AuNP chains and bracelets.

PMID- 21072400
TI  - Metal complexes with carbene ligands stabilized by lateral enamines.
AB  - Metal complexes carrying a new class of singlet carbene ligands stabilized by
      lateral enamine moieties are accessible by oxidative insertion into readily
      available chloro vinamidinium salts.

PMID- 21072401
TI  - Scandium terminal imido complex induced C-H bond selenation and formation of an
      Sc-Se bond.
AB  - The reaction between scandium terminal imido complexes and elemental selenium
      showed an unprecedented C-H bond selenation and the formation of an Sc-Se bond.

PMID- 21072402
TI  - Dihydrogen activation by sulfido-bridged dinuclear Ru/Ge complexes: insight into
      the [NiFe] hydrogenase unready state.
AB  - A S/SH bridged hetero-dinuclear Ru/Ge complex cation reacted with H(2) to afford
      the MU-S/MU-H complex. The reaction was considerably slower compared to that of
      the MU-S/MU-OH complex. Thus, the MU-S/MU-SH and MU-S/MU-OH complexes might
      provide models for the unready and ready states, respectively, of [NiFe]
      hydrogenase.

PMID- 21072403
TI  - Construction of a FRET-based ratiometric fluorescent thiol probe.
AB  - We have rationally constructed a novel FRET-based ratiometric thiol probe
      suitable for ratiometric imaging in living cells based on the native chemical
      ligation reaction.

PMID- 21072404
TI  - Thermodynamic investigations of methyl tert-butyl ether and water mixtures.
AB  - Interactions between methyl tert-butyl ether (MTBE) and water have been
      investigated by scanning calorimetry, isothermal titration calorimetry,
      densitometry, IR-spectroscopy, and gas chromatography. The solubilization of MTBE
      in water at 25  degrees C at infinite dilution has DeltaH degrees  = -17.0 +/-
      0.6 kJ mol(-1); DeltaS degrees  = -80 +/- 2 J mol(-1) K(-1); DeltaC(p) = +332 +/-
      15 J mol(-1) K(-1); DeltaV degrees  = -18 +/- 2 cm(3) mol(-1). The signs of these
      thermodynamic functions are consistent with hydrophobic interactions. The
      occurrence of hydrophobic interaction is further substantiated as IR absorption
      spectra of MTBE-water mixtures show that MTBE strengthens the hydrogen bond
      network of water. Solubilization of MTBE in water is exothermic whereas
      solubilization of water in MTBE is endothermic with DeltaH degrees  = +5.3 +/-
      0.6 kJ mol(-1). The negative mixing volume is explained by a large negative
      contribution due to size differences between water and MTBE and by a positive
      contribution due to changes in the water structure around MTBE. Henry's law
      constants, K(H), were determined from vapor pressure measurements of mixtures
      equilibrated at different temperatures. A van't Hoff analysis of K(H) gave
      DeltaH(H) degrees  = 50 +/- 1 kJ mol(-1) and DeltaS(H) degrees  = 166 +/- 5 J
      mol(-1) K(-1) for the solution to gas transfer. MTBE is excluded from the ice
      phase water upon freezing MTBE-water mixtures.

PMID- 21072405
TI  - Superior Z->E and E->Z photoswitching dynamics of dihydrodibenzodiazocine, a
      bridged azobenzene, by S1(npi*) excitation at lambda = 387 and 490 nm.
AB  - The ultrafast Z->E and E->Z photoisomerisation dynamics of 5,6
      dihydrodibenzo[c,g][1,2]diazocine (1), the parent compound of a class of bridged
      azobenzene-based photochromic molecular switches with a severely constrained
      eight-membered heterocyclic ring as central unit, have been studied by
      femtosecond time-resolved spectroscopy in n-hexane as solvent and by quantum
      chemical calculations. The diazocine contrasts with azobenzene (AB) in that its Z
      rather than E isomer is the energetically more stable form. Moreover, it stands
      out compared to AB for the spectrally well separated S(1)(npi*) absorption bands
      of its two isomers. The Z isomer absorbs at around lambda = 404 nm, the E form
      has its absorption maximum around lambda = 490 nm. The observed transient spectra
      following S(1)(npi*) photoexcitation show ultrafast excited-state decays with
      time constants tau(1) = 70 fs for the Z and <50 fs for the E isomer reflecting
      very fast departures of the excited wave packets from the S(1) Franck-Condon
      regions and tau(2) = 270 fs (320 fs) related to the Z->E (resp. E->Z)
      isomerisations. Slower transient absorption changes on the time scale of tau(3) =
      5 ps are due to vibrational cooling of the reaction products. The results show
      that the unique steric constraints in the diazocine do not hinder, but accelerate
      the molecular isomerisation dynamics and increase the photoswitching
      efficiencies, contrary to chemical intuition. The observed isomerisation times
      and quantum yields are rationalised on the basis of CASPT2//CASSCF calculations
      by a S(1)/S(0) conical intersection seam at a CNNC dihedral angle of ~96 degrees 
      involving twisting and torsion of the central CNNC moiety. With improved
      photochromism, high quantum yields, short reaction times and good photostability,
      diazocine 1 and its derivatives constitute outstanding candidates for
      photoswitchable molecular tweezers and other applications.

PMID- 21072406
TI  - High-valent diiron species generated from N-bridged diiron phthalocyanine and
      H(2)O(2).
AB  - N-bridged diiron tetra-tert-butylphthalocyanine activates H(2)O(2) to form
      anionic hydroperoxo complex [(Pc)Fe(IV)=N-Fe(III)(Pc)-OOH](-) prone to
      heterolytic cleavage of O-O bond with the release of OH(-) and formation of
      neutral diiron oxo phthalocyanine cation radical complex, PcFe(IV)=N
      Fe(IV)(Pc(+))=O. ESI-MS data showed stability of the Fe-N-Fe binuclear structure
      upon formation of this species, capable of oxidizing methane and benzene via O
      atom transfer. The slow formation kinetics and the high reactivity preclude
      direct detection of this oxo complex by low temperature UV-vis spectroscopy.
      However, strong oxidizing properties and the results of EPR study support the
      formation of PcFe(IV)=N-Fe(IV)(Pc(+))=O. Addition of H(2)O(2) at -80  degrees C
      led to the disappearance of iron EPR signal and to the appearance of the narrow
      signal at g = 2.001 consistent with the transient formation of PcFe(IV)=N
      Fe(IV)(Pc(+))=O. In the course of this study, another high valent diiron species
      was prepared in the solid state with 70% yield. The Mossbauer spectrum shows two
      quadrupole doublets with delta(1) = -0.14 mm s(-1), DeltaE(Q1) = 1.57 mm s(-1)
      and delta(2) = -0.10 mm s(-1), DeltaE(Q2) = 2.03 mm s(-1), respectively. The
      negative delta values are consistent with formation of Fe(iv) states. Fe K-edge
      EXAFS spectroscopy reveals conservation of the diiron Fe-N-Fe core. In XANES, an
      intense 1s -> 3d pre-edge feature at 7114.4 eV suggests formation of Fe(iv)
      species and attaching of one oxygen atom per two Fe atoms at the 1.90 A distance.
      On the basis of Mossbauer, EPR, EXAFS and XANES data this species was tentatively
      assigned as (Pc)Fe(IV)=N-Fe(IV)(Pc)-OH which could be formed from PcFe(IV)=N
      Fe(IV)(Pc(+))=O by hydrogen atom abstraction from a solvent molecule. Thus,
      despite unfavourable kinetics, we succeeded in the preparation of the first
      dirion(iv) phthalocyanine complex with oxygen ligand, generated in the
      (Pc)Fe(IV)=N-Fe(III)(Pc) - H(2)O(2) system capable of oxidizing methane.

PMID- 21072407
TI  - Towards high throughput production of artificial egg oocytes using microfluidics.
AB  - The production of micron-size droplets using microfluidic tools offers new
      opportunities to carry out biological assays in a controlled environment. We
      apply these strategies by using a flow-focusing microfluidic device to
      encapsulate Xenopus egg extracts, a biological system recapitulating key events
      of eukaryotic cell functions in vitro. We present a method to generate
      monodisperse egg extract-in-oil droplets and use high-speed imaging to
      characterize the droplet pinch-off dynamics leading to the production of trains
      of droplets. We use fluorescence microscopy to show that our method does not
      affect the biological activity of the encapsulated egg extract by observing the
      self-organization of microtubules and actin filaments, two main biopolymers of
      the cell cytoskeleton, encapsulated in the produced droplets. We anticipate that
      this assay might be useful for quantitative studies of biological systems in a
      confined environment as well as high throughput screenings for drug discovery.

PMID- 21072408
TI  - 10th anniversary issue: Korea.

PMID- 21072409
TI  - Systems biology of ovine intestinal parasite resistance: disease gene modules and
      biomarkers.
AB  - This study reports on the molecular systems biology of gastrointestinal nematode
      (GIN) infection and potential biomarkers for GIN resistance in sheep. Microarray
      gene expression data were obtained for 3 different tissues at 4 time points from
      sheep artificially challenged with two types of nematodes, Haemonchus contortus
      (HC) and Trichostrongylus colubriformis (TC). We employed an integrated systems
      biology approach, integrating 3 main methods: standard differential gene
      expression analyses, weighted gene co-expression network analyses (WGCNA) and
      quantitative genetic analyses of gene expression traits of key biomarkers. Using
      standard differential gene expression analyses we identified differentially
      expressed genes (DE) which responded differently in sheep challenged with HC
      compared to those challenged with TC. These interaction genes (e.g. MRPL51,
      SMEK2, CAT, MAPK1IP1 and SLC25A20A) were enriched in Wnt receptor signalling
      pathway (p = 0.0132) and positive regulation of NFkappabeta transcription factor
      activity (p = 0.00208). We report FCER1A, a gene encoding a high-affinity
      receptor for the Fc region of immunoglobulin E, which is linked to innate
      immunity to GIN in sheep. Using weighted gene co-expression network analysis
      (WGCNA) methods, we identified gene modules that were correlated with the length
      of infection (disease modules). Hub genes (with high intramodular connectivity)
      were filtered further to identify biomarkers that are related to the length of
      infection (e.g. CAT, FBX033, COL15A1, IGFBP7, FBLN1 and IgCgamma). The biomarkers
      we found in HC networks were significantly associated with functions such as T
      cell and B-cell regulations, TNF-alpha, interleukin and cytokine production. In
      TC networks, biomarkers were significantly associated with functions such as
      protein catabolic process, heat shock protein binding, protein targeting and
      localization, cytokine receptor binding, TNF receptor binding, apoptosis and IGF
      binding. These results provide specific gene targets for therapeutic
      interventions and provide insights into GIN infections in sheep which may be used
      to infer the same in related host species. This is also the first study to apply
      the concept of estimating breeding values of animals to expression traits and
      reveals 11 heritable candidate biomarkers (0.05 to 0.92) that could be used in
      selection of animals for GIN resistance.

PMID- 21072410
TI  - Rapid chemical ligation of oligonucleotides by the Diels-Alder reaction.
AB  - Extremely fast and efficient Diels-Alder chemical ligation of furan and maleimide
      oligonucleotides has been carried out in aqueous buffer. It was possible to
      ligate three oligonucleotides simultaneously in a controlled manner with the aid
      of a complementary splint. The templated reactions proceeded within 1 min at room
      temperature whereas non-templated reactions were slow and incomplete. Rapid and
      clean methods of DNA ligation such as the one demonstrated here have potential
      uses in biology and nanotechnology.

PMID- 21072411
TI  - Structure-enantioselectivity effects in 3,4-dihydropyrimido[2,1-b]benzothiazole
      based isothioureas as enantioselective acylation catalysts.
AB  - The catalytic activity and enantioselectivity in the kinetic resolution of (+/-)
      1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1
      b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts
      screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good
      levels of selectivity in the kinetic resolution of a number of secondary alcohols
      (S values up to >100 at ~50% conversion). Low catalyst loadings (0.10-0.25 mol%)
      of the optimal isothiourea can be used to generate enantiopure alcohols (>99% ee)
      in good yields.

PMID- 21072412
TI  - Revising the mechanism of polymer autooxidation.
AB  - The basic scheme for autooxidation of polymers, originally developed by Bolland,
      Gee and co-workers for rubbers and lipids, is now widely applied to all types of
      polymeric materials. According to their scheme, the reaction that makes this
      process autocatalytic, referred to as the propagation step, is a hydrogen
      abstraction from the next substrate by the peroxyl radical (ROO + RH -> ROOH +
      R). In this study, using advanced quantum-chemical methods, we have shown that
      this step is actually characterised by largely positive Gibbs free energy (10-65
      kJ mol(-1)) for most regular polymers with saturated chains (polypropylene,
      polyethylene, polyvinyl chloride, polyvinyl acetate, polyurethane, poly(methyl
      methacrylate) etc.) and even some polymers with unsaturated fragments
      (polystyrene, polyethylene terephthalate). Neither elevated temperature, nor
      solvation makes this process thermodynamically favourable. Only when the formed
      radical centre is conjugated with adjacent double bonds (as in polybutadiene) or
      captodatively stabilised by two suitable functional groups (such as a carbonyl
      and a lone pair donor such as oxygen or nitrogen), is the propagation step
      exoergic. Instead, we show that it is the presence of structural defects, such as
      terminal or internal double bonds, formed either during polymerisation or in the
      degradation process itself, that is responsible for the autooxidation of most
      polyesters and most polyalkenes. Recognition of the real mechanism of
      autooxidation in polymers is a key to developing strategies for the prevention of
      their degradation.

PMID- 21072413
TI  - Phase behaviour and conductivity study of electrolytes in supercritical
      hydrofluorocarbons.
AB  - The purpose of this work was to characterise supercritical hydrofluorocarbons
      (HFC) that can be used as solvents for electrodeposition. The phase behaviour of
      CHF(3), CH(2)F(2), and CH(2)FCF(3) containing [NBu(n)(4)][BF(4)],
      [NBu(n)(4)][B{3,5-C(6)H(3)(CF(3))(2)}(4)] and Na[B{3,5-C(6)H(3)(CF(3))(2)}(4)]
      was studied and the conditions for forming a single supercritical phase
      established. Although all three HFCs are good solvents for [NBu(n)(4)][BF(4)] the
      results show that the CH(2)F(2) system has the lowest p(r) for dissolving a given
      amount of [NBu(n)(4)][BF(4)]. The solubility of Na[B{3,5-C(6)H(3)(CF(3))(2)}(4)]
      in CH(2)F(2) was found to be unexpectedly high. Studies of the phase behaviour of
      CH(2)F(2) containing [NBu(n)(4)][BF(4)] and [Cu(CH(3)CN)(4)][BF(4)] showed that
      the copper complex was unstable in the absence of CH(3)CN. For CHF(3),
      [Cu(hfac)(2)] was more soluble and more stable than [Cu(CH(3)CN)(4)][BF(4)] and
      only increased the phase-separation pressure by a moderate amount. Studies of the
      conductivity of [NBu(n)(4)][B(C(6)F(5))(4)], [NBu(n)(4)][B{3,5
      C(6)H(3)(CF(3))(2)}(4)], [NR(f)Bu(n)(3)][B{3,5-C(6)H(3)(CF(3))(2)}(4)] (R(f) =
      (CH(2))(3)C(7)F(15)), and Na[B{3,5-C(6)H(3)(CF(3))(2)}(4)] were carried out in
      scCH(2)F(2). The results show that these salts are more conducting than
      [NBu(n)(4)][BF(4)] under the same conditions although the increase is much less
      significant than that reported in previous work in supercritical CO(2) + CH(3)CN.
      Consequently, either [NBu(n)(4)][BF(4)] or the corresponding BARF salts would be
      suitable background electrolytes for electrodeposition from scCH(2)F(2).

PMID- 21072414
TI  - Stable heteroleptic complexes of divalent lanthanides with bulky pyrazolylborate
      ligands--iodides, hydrocarbyls and triethylborohydrides.
AB  - The reaction of YbI(2) with KTp(Me2) gives (Tp(Me2))YbI(THF)(2) (1-Yb) as a
      thermally unstable product. Use of the more hindered KTp(tBu,Me) gave
      (Tp(tBu,Me))LnI(THF)(n) (Ln = Sm, n = 2, 2-Sm; Ln = Yb, n = 1, 2-Yb). The crystal
      structures of both these compounds are reported. Adducts with neutral ligands
      such as pyridines and isonitriles can be prepared and the crystal structures of
      [(Tp(tBu,Me))YbIL(n)] (L = CN(t)Bu, n = 1; L = 3,5-lutidine, n = 2) are
      described. 2-Sm can be oxidized using AgBPh(4) to give
      [(Tp(tBu,Me))SmI(THF)(2)]BPh(4). Compounds 2-Sm and 2-Yb are useful starting
      materials for the preparation of heteroleptic compounds by metathesis with
      appropriate potassium reagents. The preparations and characterization of the
      hydrocarbyls (Tp(tBu,Me))Ln{CH(SiMe(3))(2)} (Ln = Sm, 5-Sm; Yb, 5-Yb) and
      [(Tp(tBu,Me))Ln{CH(2)(SiMe(3))}(THF)] (Ln = Yb, 6a-Yb) and the
      triethylborohydrides [(Tp(tBu,Me))Ln(HBEt(3))(THF)(n)] (Ln = Sm, n = 0, 7-Sm; Yb,
      n = 1, 7-Yb) are reported, as well as the crystal structures of 5-Sm and 5-Yb,
      and the THF adducts 6a-Yb and [(Tp(tBu,Me))Sm{CH(SiMe(3))(2)}(THF)], 5a-Sm.

PMID- 21072415
TI  - Lateral and cross-lateral focusing of spherical particles in a square
      microchannel.
AB  - The inertial migration of particles in micro-scale flows has received much
      attention due to its promising applications, such as the membrane-free passive
      separation of particles or cells. The particles suspended in rectangular channels
      are known to be focused near the center of each channel face as the channel
      Reynolds number (R(C)) increases due to the lift force balance and the
      hydrodynamic interactions of the particles with the wall. In this study, the
      three-dimensional positions of neutrally buoyant spherical particles inside a
      square microchannel are measured using the digital holographic microscopy
      technique, and a transition from the lateral tubular pinch to the cross-lateral
      focusing with increasing R(C) is reported. The particles are found to migrate
      first in the lateral direction and then cross-laterally toward the four
      equilibrium positions. A general criterion that can be used to secure the fully
      developed state of particle focusing in Lab-on-a-Chip applications is also
      derived. This criterion could be helpful for the accurate estimation of the
      design parameters of inertial microfluidic devices, such as R(C), channel length
      and width, and particle diameter.

PMID- 21072416
TI  - Droplet synthesis of well-defined block copolymers using solvent-resistant
      microfluidic device.
AB  - Well-defined diblock copolymers were synthesized via an exothermic RAFT route by
      a droplet microfluidic process using a solvent-resistant and thermally stable
      fluoropolymer microreactor fabricated by a non-lithographic embedded template
      method. The resulting polymers were compared to products obtained from continuous
      flow capillary reactor and conventional bulk synthesis. The droplet based
      microreactor demonstrated superior molecular weight distribution control by
      synthesizing a higher molecular weight product with higher conversion and narrow
      polydispersity in a much shorter reaction time. The high quality of the as
      synthesized block copolymer PMMA-b-PS led to a generation of micelles with a
      narrow size distribution that could be used as a template for well-ordered
      mesoporous silica with regular frameworks and high surface areas.

PMID- 21072417
TI  - Changes of the near-surface chemical composition of the 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide room temperature ionic liquid
      under the influence of irradiation.
AB  - Radiation induced degradation effects are studied for a model ionic liquid (IL)-
      [EMIm]Tf(2)N--in order to distinguish in which way the results of X-ray based
      material analysis methods can be falsified by the radiation supplied by typical X
      ray sources itself. Photoelectron spectroscopy is commonly used for determining
      the electronic structure of ionic liquids. Degradation effects, which often occur
      e.g. in organic materials during X-ray or electron irradiation, are potentially
      critical for the interpretation of data obtained from ionic liquids. The changes
      of the chemical composition as well as the radiation-induced desorption of 1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIm]Tf(2)N)
      fragments are analysed by X-ray photoelectron spectroscopy (XPS) as well as
      quadrupole mass spectroscopy (QMS) upon exposure to monochromated or non
      monochromated AlKalpha X-rays from typical laboratory sources. During the
      irradiation of [EMIm]Tf(2)N, an increasing carbon concentration is observed in
      both cases and especially the [Tf(2)N](-) ion is strongly altered. This
      observation is supported by the results from the QMS analysis which revealed a
      variety of different IL fragments that are desorbed during X-ray irradiation. It
      is shown that the decomposition rate is directly linked to the photon flux on the
      sample and hence has to be considered when planning an XPS experiment. However,
      for typical experiments on this particular IL the measurements suggest that the
      changes are on a larger time scale as typically required for spectra acquisition,
      in particular if monochromated X-ray sources are used.

PMID- 21072418
TI  - Supramolecular assembly of a biomineralizing antimicrobial peptide in coarse
      grained Monte Carlo simulations.
AB  - Monte Carlo simulations are used to model the self-organizing behavior of the
      biomineralizing peptide KSL (KKVVFKVKFK) in the presence of phosphate. Originally
      identified as an antimicrobial peptide, KSL also directs the formation of
      biosilica through a hypothetical supramolecular template that requires phosphate
      for assembly. Specificity of each residue and the interactions between the
      peptide and phosphate are considered in a coarse-grained model. Both local and
      global physical quantities are calculated as the constituents execute their
      stochastic motion in the presence and absence of phosphate. Ordered peptide
      aggregates develop after simulations reach thermodynamic equilibrium, wherein
      phosphates form bridging ligands with lysines and are found interdigitated
      between peptide molecules. Results demonstrate that interactions between the
      lysines and phosphate drive self-organization into lower energy conformations of
      interconnected peptide scaffolds that resemble the supramolecular structures of
      polypeptide- and polyamine-mediated silica condensation systems. Furthermore, the
      specific phosphate-peptide organization appears to mimic the zwitterionic
      structure of native silaffins (scaffold proteins of diatom shells), suggesting a
      similar template organization for silica deposition between the in vitro KSL and
      silaffin systems.

PMID- 21072419
TI  - Photophysics and reductive quenching reactivity of gadusol in solution.
AB  - The photostability and photophysics of gadusol in aqueous solution has been
      studied. The photodecomposition quantum yields (ca. 4 * 10(-2) and 1 * 10(-4) at
      acidic and neutral pH, respectively) confirm the high photostability of the
      metabolite, independently of the presence of oxygen, under physiological
      conditions. The nature of the electronic transition of gadusol has been assigned
      as pi->pi* on the basis of the solvatochromic shifts of the UV absorption
      spectrum and the time-dependent density functional theory calculation of the
      vertical transition energies. The results from the photoacoustic calorimetry
      point to the rapid non-radiative decay as the dominant relaxation pathway of the
      excited species at pH 7, which is consistent with the proposed UV-sunscreening
      role of the molecule in the early atmosphere. Laser flash photolysis experiments
      probed that the ground state of the enolate form (gadusolate) undergoes electron
      transfer reactions with some triplet sensitizers in water or methanol solution. A
      rate constant of 2 * 10(8) M(-1) s(-1) has been determined for the quenching of
      rose bengal triplet state in water at pH 7. This reductive quenching reactivity
      may be considered as one of the underlying mechanisms that support the
      antioxidant capacity of gadusol in biological environments.

PMID- 21072420
TI  - Dye-loaded zeolite L @silica core-shell composite functionalized with
      europium(III) complexes for dipicolinic acid detection.
AB  - Novel core-shell composites have been developed by immobilization of non
      luminescent europium(III) complexes onto the surface of silica shells that are
      coated on the surface of luminescent dye-loaded zeolite L nano-crystals. The
      obtained core-shell composites were used for the ratiometric detection of
      dipicolinic acid (DPA) molecules. The dyes located in the channels of the zeolite
      L host are protected from any interaction with the environment of the particles
      and therefore provide a stable reference signal which can eliminate the need for
      instrument-specific calibration curves for DPA quantification in an analyte.

PMID- 21072422
TI  - Ion-molecule reactions of ammonia clusters with C60 aggregates embedded in helium
      droplets.
AB  - Helium nanodroplets are co-doped with C(60) and ammonia. Mass spectra obtained by
      electron ionization reveal cations containing ammonia clusters complexed with up
      to four C(60) units. The high mass resolution of Deltam/m~ 1/6000 makes it
      possible to separate the contributions of protonated, unprotonated and
      dehydrogenated ammonia. C(60) aggregates suppress the proton-transfer reaction
      which usually favors the appearance of protonated ammonia cluster ions.
      Unprotonated C(x)(NH(3))(n)(+) ions (x = 60, 120, 180) exceed the abundance of
      the corresponding protonated ions if n < 5; for larger values of n the abundances
      of C(60)(NH(3))(n)(+) and C(60)(NH)(n-1)NH(4)(+) become about equal.
      Dehydrogenated C(60)NH(2)(+) ions are relatively abundant; their formation is
      attributed to a transient doubly charged C(60)-ammonia complex which forms either
      by an Auger process or by Penning ionization following charge transfer between
      the primary He(+) ion and C(60). The abundance of C(x)NH(3)(+) and C(x)NH(4)(+)
      ions (x = 120 or 180) is one to two orders of magnitude weaker than the abundance
      of ions containing one or two additional ammonia molecules. However, a model
      involving evaporation of NH(3) or NH(4) from the presumably weakly bound
      C(x)NH(3)(+) and C(x)NH(4)(+) ions is at odds with the lack of enhancement in the
      abundance of C(120)(+) and C(180)(+). Mass spectra of C(60) dimers complexed with
      water complement a previous study of C(60)(H(2)O)(n)(+) recorded at much lower
      mass resolution.

PMID- 21072424
TI  - Site-selective Suzuki-Miyaura cross-coupling reactions of 2,3,4,5
      tetrabromofuran.
AB  - Suzuki-Miyaura reactions of 2,3,4,5-tetrabromofuran allow a convenient and site
      selective synthesis of mono-, di- and tetraarylfurans which are not readily
      available by other methods.

PMID- 21072421
TI  - Cu(II) catalyzed oxidation-[3+2] cycloaddition-aromatization cascade: efficient
      synthesis of pyrrolo [2, 1-a] isoquinolines.
AB  - A novel and synthetically efficient Cu(II) catalyzed oxidation-dipolar
      cycloaddition-aromatization cascade reaction has been developed for a "one-pot"
      synthesis of biologically important pyrrolo [2, 1-a] isoquinolines.

PMID- 21072425
TI  - Photosciences: a look into the future.

PMID- 21072426
TI  - pH-responsive polysaccharide microcapsules through covalent bonding assembly.
AB  - Biocompatible and biodegradable microcapsules were fabricated by the covalent
      assembly of polysaccharides and their derivatives. The formation of Schiff's
      bases between polysaccharides and their derivatives enabled the microcapsules'
      autofluorescence properties and pH-responsivity. These polysaccharide
      microcapsules have great potential applications in biological tracing and drug
      delivery.

PMID- 21072427
TI  - Linking [2]rotaxane wheels to create a new type of metal organic rotaxane
      framework.
AB  - Three new [2]rotaxanes with aromatic nitrogen donors appended to the crown ether
      wheel have been synthesized and used as ligands to coordinate Cd(II) ions. One of
      these yields a new type of 2-periodic, metal organic rotaxane framework in which
      the wheel rather than the axle is used to link the metal nodes.

PMID- 21072428
TI  - Exploring both sequence detection and restriction endonuclease cleavage kinetics
      by recognition site via single-molecule microfluidic trapping.
AB  - We demonstrate the feasibility of a single-molecule microfluidic approach to both
      sequence detection and obtaining kinetic information for restriction
      endonucleases on dsDNA. In this method, a microfluidic stagnation point flow is
      designed to trap, hold, and linearize double-stranded (ds) genomic DNA to which a
      restriction endonuclease has been pre-bound sequence-specifically. By introducing
      the cofactor magnesium, we determine the binding location of the enzyme by the
      cleavage process of dsDNA as in optical restriction mapping, however here the DNA
      need not be immobilized on a surface. We note that no special labeling of the
      enzyme is required, which makes it simpler than our previous scheme using
      stagnation point flows for sequence detection. Our accuracy in determining the
      location of the recognition site is comparable to or better than other single
      molecule techniques due to the fidelity with which we can control the
      linearization of the DNA molecules. In addition, since the cleavage process can
      be followed in real time, information about the cleavage kinetics, and subtle
      differences in binding and cleavage frequencies among the recognition sites, may
      also be obtained. Data for the five recognition sites for the type II restriction
      endonuclease EcoRI on lambda-DNA are presented as a model system. While the roles
      of the varying fluid velocity and tension along the chain backbone on the
      measured kinetics remain to be determined, we believe this new method holds
      promise for a broad range of studies of DNA-protein interactions, including the
      kinetics of other DNA cleavage processes, the dissociation of a restriction
      enzyme from the cleaved substrate, and other macromolecular cleavage processes.

PMID- 21072429
TI  - Development of a real-world direct interface for integrated DNA extraction and
      amplification in a microfluidic device.
AB  - Integrated DNA extraction and amplification have been carried out in a
      microfluidic device using electro-osmotic pumping (EOP) for fluidic control. All
      the necessary reagents for performing both DNA extraction and polymerase chain
      reaction (PCR) amplification were pre-loaded into the microfluidic device
      following encapsulation in agarose gel. Buccal cells were collected using
      OmniSwabs [WhatmanTM, UK] and manually added to a chaotropic binding/lysis
      solution pre-loaded into the microfluidic device. The released DNA was then
      adsorbed onto a silica monolith contained within the DNA extraction chamber and
      the microfluidic device sealed using polymer electrodes. The washing and elution
      steps for DNA extraction were carried out using EOP, resulting in transfer of the
      eluted DNA into the PCR chamber. Thermal cycling, achieved using a Peltier
      element, resulted in amplification of the Amelogenin locus as confirmed using
      conventional capillary gel electrophoresis. It was demonstrated that the PCR
      reagents could be stored in the microfluidic device for at least 8 weeks at 4 
      degrees C with no significant loss of activity. Such methodology lends itself to
      the production of 'ready-to-use' microfluidic devices containing all the
      necessary reagents for sample processing, with many obvious applications in
      forensics and clinical medicine.

PMID- 21072431
TI  - Electrochemical sensing for caspase 3 activity and inhibition using quantum dot
      functionalized carbon nanotube labels.
AB  - A novel electrochemical sensing platform for sensitive determination of caspase 3
      activity and inhibition was developed by combining the site-specific recognition
      and cleavage of the DEVD-peptide with quantum dots as signal amplification.

PMID- 21072432
TI  - Single-crystal alpha-Fe2O3 hexagonal nanorings: stepwise influence of different
      anionic ligands (F- and SCN- anions).
AB  - Single-crystal alpha-Fe(2)O(3) hexagonal nanorings with hexagonal inner hole were
      synthesized under the stepwise influence of different anionic ligands (F(-) and
      SCN(-)). This is a new method to design and modify crystal structures of
      transition metal oxide nanoparticles.

PMID- 21072433
TI  - Small molecules control the formation of Pt nanocrystals: a key role of carbon
      monoxide in the synthesis of Pt nanocubes.
AB  - In many previous studies, nonaqueous synthesis of Pt nanocubes with tunable size
      has been achieved by the use of metal carbonyls (e.g., Fe(CO)(5), Co(2)(CO)(8),
      W(CO)(6)). The presence of zero-valent metals in the carbonyls was demonstrated
      as the key factor to the nanocube formation but the role of CO was entirely
      ignored. By using CO alone, we have now demonstrated that the favorable growth of
      Pt nanocubes in the presence of CO is mainly owing to the effect that the Pt
      (100) surface is stabilized by the co-adsorption of CO and amine.

PMID- 21072434
TI  - Multimodal coupling of optical transitions and plasmonic oscillations in
      rhodamine B modified gold nanoparticles.
AB  - The optical properties of a photoluminescent dye rhodamine B (RhB) interacting
      with gold nanoparticles (AuNP) have been investigated using plasmonic absorbance,
      fluorescence, and resonance elastic light scattering (RELS) spectroscopy. We have
      found that these interactions result in a multimodal coupling that influence
      optical transitions in RhB. In absorbance measurements, we have observed for the
      first time the coupling resulting in strong screening of RhB pi-pi* transitions,
      likely caused by a contact adsorption of RhB on a conductive surface of AuNP. The
      nanoparticles quench also very efficiently the RhB fluorescence. We have
      determined that the static quenching mechanism with a non-Forster fluorescence
      resonance energy transfer (FRET) from RhB molecules to AuNP is involved. The
      Stern-Volmer dependence F(0)/F = f(Q) shows an upward deviation from linearity,
      attributed to the ultra-high quenching efficiency of AuNP leading to the new
      extended Stern-Volmer model. A sharp RELS peak of RhB alone (lambda(max) = 566
      nm) has been observed for the first time and attributed to the resonance
      fluorescence and enhanced scattering. This peak is completely quenched in the
      presence of AuNP(22nm). Our quantum mechanical calculations confirm that the
      distance between AuNP surface and conjugated pi-electron system in RhB is well
      within the range of plasmonic fields extending from AuNP. The optical transition
      coupling to plasmonic oscillations and the efficient energy transfer due to the
      interactions of fluorescent dyes with nanoparticles are important for biophysical
      studies of life processes and applications in nanomedicine.

PMID- 21072435
TI  - Hydrophoretic high-throughput selection of platelets in physiological shear
      stress range.
AB  - A gentle, but fast means for low-stress, high-throughput platelet purification is
      of significant clinical and biotechnological utility. Current implementations to
      sort platelets, however, require an external physical field, specialized buffer,
      or the harsh separation condition of high shear stress that tends to cause
      platelet stimulation. Here we report the use of hydrophoretic size separation in
      a wider channel and its parallelization to augment its throughput capability,
      maintaining physiological shear-stress range. We demonstrate a parallelized
      device comprising 10 stacks of the wide-channel hydrophoresis device, yielding a
      throughput of 2.9 million cells s(-1) and a platelet purity of 76.8%. The use of
      the wide channel for hydrophoresis also facilitates clogging-free separation by
      sorting blood clots and plaques. The wide-channel hydrophoresis offers the
      potential for gentle, fast, clogging-free sorting of rare blood cells with
      extreme throughput capabilities.

PMID- 21072436
TI  - Single-crystalline alpha-Fe2O3 oblique nanoparallelepipeds: high-yield synthesis,
      growth mechanism and structure enhanced gas-sensing properties.
AB  - In this paper, single-crystalline alpha-Fe2O3 oblique nanoparallelepipeds are
      fabricated in high yield via a facile surfactant-free hydrothermal method, which
      involves oriented aggregation and Ostwald ripening. The obtained nanocrystals
      have exposed facets of {012}, {01-4} and {-210} with a rhombohedral alpha-Fe2O3
      structure. The gas sensors based on the as-synthesized alpha-Fe2O3 nanostructures
      exhibit high sensitivity, short recovery time, and good reproducibility in
      ethanol and acetone. The superiority of the gas-sensing properties of the
      obtained nanostructures should be attributed to the surface structure of the
      nanocrystals. The as-prepared alpha-Fe2O3 nanocrystals are significant for
      exploiting their other applications in the future.

PMID- 21072437
TI  - Hydrogen-bond strengths by magnetically induced currents.
AB  - We present here a "non-invasive" computational method to estimate the strength of
      individual hydrogen bonds using magnetically induced currents. The method is
      calibrated using H-bonding dimers, and applied on Watson-Crick DNA base pairs and
      proton wires in carbonic anhydrase.

PMID- 21072430
TI  - Natural products as a source of Alzheimer's drug leads.
AB  - This review focuses on recent developments in the use of natural products as
      therapeutics for Alzheimer's disease. The compounds span a diverse array of
      structural classes and are organized according to their mechanism of action, with
      the focus primarily on the major hypotheses. Overall, the review discusses more
      than 180 compounds and summarizes 400 references.

PMID- 21072438
TI  - Molecular dynamics calculation of activation volumes.
AB  - We propose a novel approach toward calculating activation and reaction volumes
      based on MD simulations of reaction systems. The accuracy of the calculated
      volumes, verified by the comparison to the experimental data, is suitable for
      quantitative analysis of the experimental volumes of activations in terms of
      structural parameters of the corresponding transition states.

PMID- 21072439
TI  - High-resolution solid-state (13)C MUMAS NMR with long coherence life times.
AB  - Longer coherence life times (i.e. smaller homogeneous linewidths) can be achieved
      for carbon resonances which are strongly coupled to protons with high rf field
      heteronuclear decoupling in micro magic angle spinning NMR. Better proton
      decoupling enhances the sensitivity and resolution of two-dimensional through
      bond correlation experiments for mass-limited samples with uniform carbon
      labeling.

PMID- 21072440
TI  - Time-of-flight thermal flowrate sensor for lab-on-chip applications.
AB  - We describe a thermal microflowrate sensor for measuring liquid flow velocity in
      microfluidic channels, which is capable of providing a highly accurate response
      independent of the thermal and physical properties of the working liquid. The
      sensor consists of a rectangular channel containing a heater and several
      temperature detectors microfabricated on suspended silicon bridges. Heat pulses
      created by the heater are advected downstream by the flow and are detected using
      the temperature detector bridges. By injecting a pseudo-stochastic thermal signal
      at the heater and performing a cross correlation between the detected and the
      injected signals, we can measure the single-pulse response of the system with
      excellent signal-to-noise ratio and hence deduce the thermal signal time-of
      flight from heater to detector. Combining results from several detector bridges
      allows us to eliminate diffusion effects, and thus calculate the flow velocity
      with excellent accuracy and linearity over more than two orders of magnitude. The
      experimental results obtained with several test fluids closely agree with data
      from finite element analysis. We developed a phenomenological model which
      supports and explains the observed sensor response. Several fully functional
      sensor prototypes were built and characterized, proving the feasibility and
      providing a critical component to microfluidic lab-on-chip applications where
      accurate flow measurements are of importance.

PMID- 21072441
TI  - Proteomics investigation of human platelets in healthy donors and cystic fibrosis
      patients by shotgun nUPLC-MSE and 2DE: a comparative study.
AB  - Platelets are of pathophysiological relevance in haemostasis, wound repair,
      inflammation and cardiovascular disease. We have shown that human platelets
      express a biologically active Cystic Fibrosis Transmembrane Conductance
      Regulator, which is dysfunctional in Cystic Fibrosis (CF) patients, and regulate
      platelet responses related to inflammation and its resolution. In order to
      further elucidate platelet involvement in CF inflammation, we pursued a
      comparative proteomic analysis of cells from healthy donors and CF patients, in
      association with a non-supervised comparative analysis of the Gene Ontology. Our
      results, showing changes in the integrin signalling in CF, support a pro
      inflammatory profile of CF platelets.

PMID- 21072442
TI  - [Advances and challenges of the Revista Peruana de Medicina Experimental y Salud
      Publica in the year 2010].

PMID- 21072443
TI  - [Interculturality in health. The new frontier of medicine].

PMID- 21072444
TI  - [Tuberculosis in the indigenous population of Peru 2008].
AB  - OBJECTIVE: To identify the indigenous inhabitants affected by tuberculosis (TB)
      in Peru during the year 2008. MATERIAL AND METHODS: Descriptive observational
      study, performed from August to December 2009, including all indigenous patients
      affected by tuberculosis that were including in the Control Program during the
      year 2008 in the 25 regions of Peru. RESULTS: We identified 702 indigenous
      patients with tuberculosis. The ethnical groups that have most patients were the
      Quechua group (417/702; 59.4%) and the Amazonic indigenous (201/702, 28.6%). Out
      of the Amazonic, more than 60% belonged to the Ashaninka (Campas), Shipibo and
      Matsiguenga groups. In third place, we found the Aymara natives, who had 84/702
      (11.97%) of cases of tuberculosis. It is important to mention that the
      distribution of the cases of multidrugresistant tuberculosis (MDR TB) involves
      five departments (nine cases of MDR TB), being the greater number of cases of MDR
      TB in patients previously treated (6/9), and only 3 cases were primary MDR TB,
      belonging to the quechua group. CONCLUSIONS: High incidence rates of tuberculosis
      in indigenous population have been found, which raises the need of further
      research in order to guarantee the correct gathering of information in ethnic
      groups in order to have more and better evidence about the situation of
      tuberculosis in the indigenous population of Peru.

PMID- 21072445
TI  - [Concurrent infections by two dengue virus serotypes during an outbreak in
      northwestern Peru, 2008].
AB  - OBJECTIVES: To establish the existence of concurrent infections by different
      dengue virus (DENV) serotypes in an outbreak in the Northwestern in Peru during
      2008. MATERIAL AND METHODS: 73 serum samples from patients with dengue were
      analyzed during an outbreak that occurred in Northwestern in Peru between May and
      June 2008. Molecular biology techniques were used to serotype the DENV, thus,
      firstly the viral RNA viral was extracted using Viral QIAamp RNA mini kit
      (Qiagen, Valencia, California, USA), then the viral cDNA fragments were reverse
      transcripted and amplified by means of the Reverse Transcriptase Polymerase Chain
      Reaction (RT-PCR) and the RT-Nested PCR region techniques and finally, genetic
      sequencing of the viral cDNA fragments were performed using the Big Dye
      Terminator v.3,1 kit. RESULTS: The 73 dengue cases presented infections by
      different serotypes: 34 (46.6%) by DENV-3, 29 (39.7%) by DENV-1, 4 (5.5%) by DENV
      4, and 6 (8.2%) concurrent infections by DENV-1 and DENV-3. The most frequent
      clinical manifestations observed among dengue patients were fever and headache
      (100%), myalgia (94.5%), ocular pain (83.6%), arthralgia (78.1%), shivers
      (63.0%), nausea/vomiting (38.4%), positive tourniquet test (30.1%), and rash
      (20.5%). All patients with concurrent infections presented light clinical course
      of dengue fever (DF) except one patient who had moderate hemorrhagic
      manifestations. CONCLUSION: This is the first Peruvian report of patients with
      concurrent infections of two DENV serotypes without severe clinical
      manifestations.

PMID- 21072446
TI  - [Association between cutaneous leishmaniasis incidence and the human development
      index and its components in four endemic states of Venezuela].
AB  - OBJECTIVES: Assess potential relationships between the Human Development Index
      (HDI) and its components and the incidence of cutaneous leishmaniasis (CL) in
      four endemic States of Venezuela (Merida, Trujillo, Lara and Sucre) in the period
      1994-2003. MATERIAL AND METHODS: Socioeconomical data (classified according the
      World Bank) was obtained from the National Institute of Statistics, and the
      epidemiological data from the Ministry of Health, both from Venezuela. For this
      ecological study the annual variation of the variables was assessed and also
      regression models were done. RESULTS: The HDI varied in the period from 0.6746 in
      1994 to 0.8144 in 2003 (p=0.90). During this time an increase in the cumulative
      incidence of Leishmaniasis was observed, particularly from 1998 (7.3
      cases/100,000 pop) to 1999 (11.3 cases/100,000 pop). Analyzing the linear
      regression models, it was observed that the relationship between epidemiological
      and social variables was different at States levels. For Merida and Trujillo it
      was observed a significant decrease in the CL regard to the increase of literacy
      (p<0.05), of the gross combined enrollment (p<0.05), life expectancy (p<0.05),
      money income (p<0.05) and the HDI (p<0.05). CONCLUSION: This information reflects
      the significant influence of socioeconomical indicators on the CL incidence at
      Trujillo and Merida, being an inverse relationship between both types of
      variables; with an increase or improvement in the socioeconomical indicators, the
      disease incidence rate decreased.

PMID- 21072447
TI  - [Risk sexual behavior among people living with HIV/AIDS and receiving
      antiretroviral therapy in Piura, Peru].
AB  - OBJECTIVE: To explore opinions and beliefs about risky sexual behavior and HIH
      transmission in tow hospital of Piura. MATERIAL AND METHODS: Qualitative study
      based on extensive interviews and focus groups of people over 15 years old of age
      living with HIV. Interviews were recorded as audio, and then transcribed as text
      in MS Word. Information was analyzed with AtlasTi. RESULTS: Results indicate that
      people living with HIV and receive antiretrovirals practice risky sexual
      behavior. Those results agree with quantitative-epidemiological studies
      establishing that TARGA era is associated with continuation or increase of risky
      sexual behavior. Two reasons could explain such behavior; first there is a belief
      that HIV is innocuous by effect of the antiretrovirals. Second, there is belief
      that a medical confirmation of undetectable viral count means being healed from
      infection. CONCLUSIONS: People living with HIV receiving antiretrovirals
      improving general health status maintain risky sexual behavior that may
      facilitate HIV transmission to their serodiscordant partners and increase the
      number of people infected. Until now, prevention activities mostly targeted
      people believed not to be infected, however, it is also necessary an intense
      secondary prevention effort that includes an explicit approach of sexuality in
      its entire dimension.

PMID- 21072448
TI  - [Prevalence of the attempts to stop pregnancy and associated factors in a
      marginal suburban community in Lima-Peru, 2006].
AB  - OBJECTIVES: To estimate the prevalence for the attempts to stop pregnancy among
      women with history of previous pregnancies, and to determine the factors
      associated. MATERIAL AND METHODS: A cross-sectional study was performed during
      2006. Samples included 1057 women with background of pregnancy, living in
      Pamplona Alta, selected by a systematic random sampling. We applied descriptive
      and inferential statistics, including a logistic regression model. RESULTS: The
      prevalence for the attempt to stop pregnancy was 13.9% (99% CI: 11.1-16.7). The
      factors associated identified by multivariate analysis were: Unwanted pregnancy
      (OR=5.7; CI: 1.9-16.7), lack of pre-natal care (OR=4.7; CI: 1.8-12.2),
      prostitution (OR=11.4; CI: 1.5-87.9), age below 20 years (OR=2.9; CI: 1.1-7.9),
      and having more than two partners (OR=3.3; CI: 1.1-10.2). CONCLUSIONS: The
      estimated prevalence for the attempt to stop pregnancy among women with history
      of previous pregnancies in a marginal suburban area from Lima was low when
      compared to the national estimated prevalence of abortion. The associated factors
      identified for the attempts to stop pregnancy are: unwanted pregnancy,
      prostitution, age below 20 years, having more than two partners and lack of pre
      natal care.

PMID- 21072449
TI  - [Caesarean section among seven public hospitals at Lima: trend analysis during
      2001-2008 period].
AB  - OBJECTIVE: To analyze the trend of the monthly "caesarean section rate" (CSR) at
      the DISA V Lima-Ciudad Hospitals during the period 2001 - 2008. MATERIAL AND
      METHODS: Ecological study that aim to analyze the monthly reports of all DISA V
      Lima-Ciudad Hospitals that attends childbirths, and by analyzing the trend of
      theirs monthly caesarean section ratio or monthly CSR (TCM = total caesarean
      births in a month * 100/total number of newborns in the same month ) to determine
      their characteristic patterns. RESULTS: Of the 7 hospitals studied, it was found
      that between 2001 and 2008, TCM average was 36.9% +/- 9.1% (range: 16.5%-71.4%).
      From 2001 (33.5% +/- 6.9%) to 2008 (39.7% +/- 8.3%) years TCM increased 6.9% +/-
      7.0% on average, having registered a increase of 7.7% +/- 6.4% at the year 2007
      (43.5% +/- 9.8%). Analyzing the TCM trend was found that most hospitals have a
      significant increase between 2004 and 2005 years. Analyzing the TCM trend was
      found that it tends to increase in April (37,9% +/- 9,7%) and September (40.2% +/
      8.9%), cycle that characterize most DISA V Lima-Ciudad Hospitals. CONCLUSIONS:
      TCM of the DISA V Lima-Ciudad Hospitals length exceeds the limit recommended by
      WHO and, during the period 2001-2008, has had a significant trend to increase.

PMID- 21072450
TI  - [Rapid centrifugation assay standarization for dengue virus isolation].
AB  - The plate centrifugation assay was standardized for dengue virus isolation from
      serum samples. C6/36-HT cells were used determining the optimal values for
      centrifugation spin speed, inoculum, sera dilution, and incubation time. Then, 22
      positive serum samples with viral isolation and viral strains of the four
      reference dengue virus serotypes were tested simultaneously by the standardized
      plate centrifugation method and the conventional tube culture. The isolations
      were typified by indirect immunofluorescent test using monoclonal antibodies. The
      plate centrifugation method was optimized to 200 MUL of inoculum, dilution of
      sera 1/20, centrifugation speed at 1600 rpm/30 min, and sensitivity of 95,5%
      after 5 days post-inoculation. We concluded that the plate centrifugation method
      increased dengue virus isolation, with a significant reduction of the time of
      isolation for dengue virus.

PMID- 21072451
TI  - [Knowledge, attitudes and practices about fascioliasis among mothers from an
      Andean rural area of north Peru].
AB  - A survey to determine knowledge, attitudes and practices about fascioliasis was
      administered to 62 mothers from a rural endemic zone of Cajamarca's Andean
      Region, Peru. Only 37.0% recognized the alicuya (local name for Fasciola
      hepatica) as the parasite responsible for the disease; 56.5% knows that the
      disease affects the liver in the humans and 85.5% knows affects also animals;
      98.4% have a positive predisposition to attend informative talks about the
      disease and 75.8% to support their authorities actively to solve of the problem.
      38.7% referred drinking emollients in the street, 75.6% have domestic animals
      considered host for the parasite. In conclusion, attitudes of mothers are mostly
      favourable for prevention and control activities, despite their mistaken
      knowledge risky practices for fasciolasis among members of their families.

PMID- 21072452
TI  - [High frequency of plagiarism in medical thesis from a Peruvian public
      university].
AB  - An observational study was conducted to describe the presence of plagiarism in
      medical thesis in 2008 performed at a public university in Peru. Search for
      plagiarism in 33 thesis introductions using a Google search algorithm,
      characterizes of the study type and we search in electronic form if the thesis
      mentor have published articles in scientific journals. We found evidence of
      plagiarism in 27/33 introductions, 37.3% (171/479) of all the paragraphs analyzed
      had some degree of plagiarism, literal plagiarism was the most frequent (20/27)
      and journals were the most common sources of plagiarism (19/27). The
      characteristics of the studies were observational (32/33), cross-sectional
      (30/33), descriptive (25/33) and retrospective (19/33). None of the authors had
      published in a scientific journal, and only nine of his tutors of them had at
      least one publication. No association was found between the characteristics of
      the thesis and the presence of plagiarism. In conclusion, we found a high
      frequency of plagiarism in theses analyzed. Is responsibility of medical schools
      take the necessary actions to detect and avoid plagiarism among their students.

PMID- 21072453
TI  - [Economic evaluation of antiviral treatment for chronic hepatitis B: a systematic
      review].
AB  - OBJECTIVE: To revise the available evidence on the cost-effectiveness of
      antiviral regimens for treatment of chronic hepatitis B. MATERIAL AND METHODS: We
      performed a systematic revision on MEDLINE, LILACS NICE and COCHRANE databases,
      searching for economic evaluations of antiviral regimens for treatment of chronic
      hepatitis B. We included original studies, systematic revisions and management
      guidelines including information on the cost-effectiveness of this treatment. We
      registered the characteristics and results of the retrieved documents. RESULTS:
      We obtained 29 original papers, 4 revision articles and 4 management guidelines.
      Most of these publications have been done in the last 5 years. There was conflict
      of interest in 73% of original articles, due to authors working for the
      pharmaceutical industry. 93% of articles that evaluate the cost-effectiveness of
      giving treatment for chronic hepatitis B against management of its complications
      find that it is indeed cost-effective to give antiviral treatment. 3/6 studies
      that evaluate lamivudine against other drugs find it as a dominant strategy, 3/5
      find entecavir as the dominant strategy, 1/1 find tenofovir dominant, 1/4 find
      conventional interferon as dominant and none of them find adefovir or pegylated
      interferon as dominant strategies. CONCLUSIONS: We consider that the available
      evidence suggests that to give antiviral treatment for chronic hepatitis B is a
      cost-effective intervention for many health systems, including ours. It has
      varying indexes of cost-effectiveness according to the evaluated regimens.
      Ideally , we should perform local economic evaluations in this issue.

PMID- 21072454
TI  - [Interculturality in health].
AB  - Interculturality in health is a recent concept that develops in response to
      claims of indigenous peoples for their right to their cultural identity, but also
      correspond to a global trend of incorporating the "right to the difference",
      which distinguishes and promotes coexistence between different cultural groups in
      the same territory. The article discusses, from a historical perspective, the
      original mismatch between Native American populations and European conquerors
      that marked out their access to health services, and discussed some of the many
      current issues related to, as the identification of indigenous people and the
      relationship between human rights and interculturality, to finally present a
      review of the genesis of the concept of interculturalism in health and their
      complexity reviewing the concept of cultural syndrome and his adaptation to
      scientific medicine.

PMID- 21072455
TI  - [Beyond the indigenous: health and interculturality at the global level].
AB  - Health inequalities are broadly documented for ethnic minority groups and
      immigrants worldwide. Intercultural perspectives in health are thus developed in
      very different places and situations. Both the criteria for defining the target
      groups as well as the ways the health problems of these groups are looked at, are
      shaped by the particular local context. However, some challenges are common to
      almost all situations where the topic of ethnic diversity and health is
      considered. And in contrast to the rather novel term, the issues at stake in
      "intercultural heath" are not new at all. Against this background, the present
      article brings into focus three essential points: the necessity of defining
      ethnicity adequately to avoid stereotyping and the creation of new inequalities;
      the challenge of converting ethnicity into a helpful and thus "healthy" category
      in the field of medicine and health; and the need for the integration of explicit
      and serious reflections on medical ethics and human rights that provide for the
      normative framework and moral orientation of health activities with indigenous,
      migrant and other particularly vulnerable groups.

PMID- 21072456
TI  - [Surgery and Amerindian peoples: an intercultural challenge].
AB  - Many cultures have performed the cutting and excision of the human anatomy under
      contexts that we consider magical or religious; nevertheless, the will to offer
      recovery to people in their diseases, progressively transformed these cuttings
      into procedures aimed at the extraction of their causes, known as surgery.
      However, that didn't imply a replacement but a different sight of how to provide
      health, that is why there are still gaps between that "symbolic surgery" and the
      one practiced in occident. In this review we offer a description of the vision of
      diverse communities regarding surgery, and some anecdotes of how it has
      influenced, modified or rejected the application of modern surgery.

PMID- 21072457
TI  - [Education on medical anthropology and intercultural health in Mexico: from the
      20th century cultural indigenism to the 21st century interculturality].
AB  - The study of the health/disease/healthcare process from the socio-medical aspect
      is the field of the medical anthropology. In Mexico, this medical specialty had
      its origins at the end of the 19th century. Since then, many educational reforms
      occurred associated to the political processes and the recognition and better
      understanding of Mexican pluricultural society; allowing expansion,
      diversification and consolidation of medical anthropology as an specialty. This
      review presents the historical evolution of the academic courses on this field,
      the educators that influenced its consolidation, and the current situation of the
      available academic programs on medical anthropology. The diversity of specialties
      from those health sciences that are associated to medical anthropology is
      emphasized.

PMID- 21072458
TI  - [Medical anthropology evidences on the Pishtaco origin].
AB  - This paper will contribute to the scientific development of a new approach on the
      pishtaco in Peru by means of medical anthropological analysis. The model
      emphasizes presentation and analysis of historical, pharmaceutical, and
      anthropological evidence supporting use of human tissues with specific medical
      goals in Peruvian and European regions. We can find the origin of this phenomenon
      around the sixteen and seventeen centuries in Europe: The pishtaco has no an
      Andean origin. The methodology and main conclusions of this paper could provide
      to the scientific community an alternative perspective to the conventional
      anthropological and ethnological research, as an example of a medical
      anthropological analysis of the pishtaco character. Professionals involved in
      intercultural health projects could have a new insight on this issue thanks to
      these results. They will obtain an adequate historical-cultural context for the
      interpretation and understanding of people and native communities' beliefs about
      health, body and medical systems.

PMID- 21072459
TI  - [Atypic toxocariasis: a case report from the Peruvian north coast].
AB  - We present the case of a 4.5 years old boy with atypic toxocariasis, from La
      Matanza, Morropon, Piura. The patient had non-specific symptoms during 9 days.
      Suspicion of Toxocariasis was supported by marked eosinophilia in the cell blood
      count (15% or 1470 cells/MUL). Diagnosis was confirmed by laboratory with ELISA
      serology demonstrating the presence of IgG and IgM anti-Toxocara antibodies.
      Symptoms receded before the patient received a five-day treatment with albendazol
      15mg/kg/day.

PMID- 21072460
TI  - [Telemaco Battistini Sanchez (1895-1960)].

PMID- 21072461
TI  - [M. Kuczynski-Godard (1890-1967): medical-anthropological pictures of the
      Peruvian Amazon and the Andes, 1938-1948].

PMID- 21072462
TI  - [About tuberculosis].

PMID- 21072463
TI  - [About Peruvian medical journals].

PMID- 21072465
TI  - [Road traffic injuries in Peru: where are we and what next?].

PMID- 21072466
TI  - [Epidemiological profile of road traffic accidents in Peru, 2005-2009].
AB  - OBJECTIVE: To determine the characteristics and epidemiological profile of road
      traffic injuries (RTI) in Peru during the period 2005-2009. MATERIALS AND
      METHODS: Descriptive, retrospective study, secondary sources of information on
      RTI from the National Police of Peru and the National Sanitary Strategy for the
      Control of Traffic Accidents (ESNAT) of the Ministry of Health were analyzed.
      RESULTS: During the 5 years of study, there were 404120 TA, of which 63.8%
      occurred in Lima. Cars and vans are the types of vehicle most frequently involved
      in these accidents. Speed excess and driver's senselessness are the main causes
      of accidents. The most common type of accident is the crash (57%). Males from 20
      to 34 years old are the most vulnerable population. CONCLUSIONS: The RTI are an
      emerging public health problem in Peru. The trend of the mortality and morbidity
      rates due to traffic accidents in Peru has followed an increasing curve between
      the years 2005 and 2008; however these numbers during 2009 have been decreasing
      but not really significantly. Information systems must be integrated in order to
      give reliable information to the national institutions involved in these
      problematic, so that it can be used as a reference for future political
      decisions.

PMID- 21072467
TI  - [Self-reporting of road traffic accidents in a national survey of urban
      population in Peru].
AB  - OBJECTIVES: To estimate the frequency of self-reporting of road traffic accidents
      in the previous year in the general population and to determine the associated
      factors. MATERIALS AND METHODS: We conducted a secondary analysis of the data of
      the III National Survey of Drug Use in the General Population of Peru, 2006. We
      measured socio-demographical variables: age, gender, place of origin, educational
      level and marital status. We also evaluated the use of legal, illegal and medical
      drugs. The independent variable was the self-reporting of a road traffic
      accident. We performed the descriptive, bivariate and multivariate analysis of
      the socio-demographical variables and the drug use (legal and illegal), together
      with the self-reporting of the traffic accident. RESULTS: The frequency of
      reporting of road traffic accidents in the last year according to the survey was
      2.93% (95%CI: 2.92-2.94). The associated factors for self-reporting of a road
      traffic accident were: to live in the jungle areas (OR: 2.03; 95%CI:1.55-2.65),
      male gender (OR: 1.79; 95%CI: 1.46-2.22), legal drugs use in the last year (OR:
      1.98, 95%CI: 1.53-2.55), alcohol consumption in the last year (OR: 1.82; 95%CI:
      1.44-2.32) and medical drugs use in the last year (OR: 2.45, 95%CI 1.63-3.68).
      CONCLUSIONS: The prevalence of self-reporting of road traffic accidents in the
      last year was very high compared to similar studies and other reporting sources.
      The variables associated with having had a traffic accident were: living in the
      jungle area, being male, legal drug use in the last month, especially alcohol and
      medical drug use in the last month. It is necessary to think carefully about the
      information system of the road traffic accidents in order to achieve a better
      picture of the problem putting emphasis in the legal drugs use.

PMID- 21072468
TI  - [Coverage of the Emergency Health Care Law and the Compulsory Insurance against
      Road Traffic Crashes (SOAT)].
AB  - OBJECTIVE: The aim of this study was to ascertain, from patients' perspective,
      the degree of knowledge and the actual coverage of the Emergency Health Care Law
      and the Compulsory Insurance against Road Traffic Crashes (SOAT). MATERIAL AND
      METHODS: A cross-sectional, active surveillance of emergency wards of selected
      health facilities in three Peruvian cities (Lima, Pucallpa y Ayacucho) was
      conducted. RESULTS: Out of 644 surveyed victims, 77% did not know about the law
      about provision of emergency health care (81% in Lima, 64% in Pucallpa y 93% in
      Ayacucho; p<0.001). Following the explanation of what this law entails, 46%
      reported to have received care according to the law specifications. As for SOAT,
      the health care related costs of 237 persons (37.2%) were not covered by any
      insurance scheme (74% in Pucallpa, 34% in Ayacucho and 26% in Lima: p<0.001).
      CONCLUSIONS: In this study, the lack of knowledge about the provision of
      emergency health care law was important, and the coverage of care was deficient
      as nearly half of participants reported not to be treated by one or more of the
      entitlements stated in such law. Road traffic injuriesrelated health care costs
      were not covered by any insurance scheme in one of three victims. Improvements on
      citizens? information about their rights and of effective law enforcement are
      badly needed to reach a universal and more equitable coverage in the health care
      of road traffic-related victims.

PMID- 21072469
TI  - [Fatigue and sleepiness in interprovincial road bus drivers: comparative study
      between formality and informality].
AB  - OBJECTIVES: To compare the levels of fatigue, sleepiness and their consequences
      between formal and informal drivers of interprovincial buses. To evaluate labor
      conditions between both study groups. MATERIALS AND METHODS: A comparative cross
      sectional study was performed with non-probabilistic sampling. 100 companies of
      land transport were included, out of which 17 were formal according to the
      official registries of the Ministry of Transport and Communications (MTC), the
      drivers were also classified as formal or informal. The survey included one
      questionnaire and a Peruvian validated version of the Epworth sleepiness scale.
      RESULTS: 71 formal drivers and 274 informal drivers participated, all were males.
      Out of the 134 drivers that worked for the formal companies according to the MTC,
      only 43 (32%) belong to the formal group based on the proposed criteria. 48% (34)
      of the formal drivers and 43% (118) of the informal sleep less than 7 hours a
      day. 48% (34) of the formal and 49% (135) of the informal admitted having had an
      accident or "almost" having had it, the most frequent time of the day was between
      01.00 and 04.00 in the morning. The dawn is the period in which both groups feel
      most tired. 44% (30) of the formal drivers and 54% (144) of the informal ones
      perform 5 or more night shifts per week. Out of the total of interviewed, 16%
      (56) had sleepiness. The association with road traffic accidents was similar.
      CONCLUSIONS: The fatigue and sleepiness levels were similar between formal and
      informal drivers. Companies classified as formal, have a high percentage of
      informality amongst their drivers.

PMID- 21072470
TI  - [Iodized salt intake in households and iodine nutritional status in women of
      childbearing age in Peru, 2008].
AB  - OBJECTIVE: To estimate the iodine nutritional status in women of childbearing age
      and to evaluate the intake of salt adequately iodized in their households in
      Peru. MATERIALS AND METHODS: Cross-sectional study performed with a multistage,
      probabilistic, cluster sampling that included 1573 households and 2048 women in
      childbearing age, distributed in five domains (Lima, rest of the coast, rural
      highlands and jungle area). The use of iodized salt was evaluated in the
      households and the urinary iodine was evaluated in the childbearing age women.
      RESULTS: 97.5% (95%CI. 96.7-98.5%) of peruvian households have iodized salt
      consumption, being it lower in the rural highland (95%) and higher in Lima
      (100%). The national mean of urinary iodine was 266 MUg/L, being it lower in the
      jungle areas (206 MUg/L) and higher in the rest of the coast (302 MUg/L), these
      values are above the level recommended by the World Health Organization in all
      domains (average higher than 200 MUg/L), value that ensures control over the
      iodine deficiency disorders (IDD). CONCLUSIONS: Control of IDD associated with
      iodized salt consumption is good, and monitoring of the presence of iodine in
      salt, particularly in the areas with lowest access, should continue.

PMID- 21072471
TI  - [Factors associated to complications of endoscopic retrograde
      cholangiopancreatography in a third-level hospital].
AB  - Endoscopic treatment of the bile duct diseases is possible thanks to the ERCP
      (endoscopic retrograde cholangio pancreatography), nevertheless, it is not free
      of complications. OBJECTIVES: To describe the characteristics and indications of
      the ERCP and determine the factors associated to the development of complications
      after performing the procedure. MATERIALS AND METHODS: An observational
      retrospective study was done in the Gastroenterology Department of the Hospital
      Guillermo Almenara Irigoyen in Lima, Peru, from March 2002 to June 2005. RESULTS:
      294 registers on 280 patients were evaluated, the median age was 58 and 155
      (52.7%) were women, five procedures we done in the intensive care unit (ICU). The
      most frequent indication was choledochus litiasis in 67.3% cases. 205 (69.7%)
      procedures were successful, only 33 presented complications. The most frequent
      complications were acute pancreatitis and hemorrhage, in 16 and 13 patients
      respectively. There were no cases of perforation or death. Pancreatic duct
      cannulation more than once was an associated factor (OR=2.01; 95%CI: 1.11-5.92;
      p=0.03). CONCLUSIONS: 11.2% of cases presented complications, being acute
      pancreatitis and mild hemorrhage the most frequent complications. Only pancreatic
      duct cannulation more than once is an associated factor for having complications.

PMID- 21072472
TI  - [Evaluation of two immunoblot tests with goat and sheep hydatid antigen for human
      echinococcosis diagnosis].
AB  - To estimate the diagnosis value of goat and ovine antigen for echinococcosis
      immunoblot test, 135 serums were used, of which 70 were coming from patients with
      hydatid disease confirmed by the finding of proto scolex and membrane in the
      pathology study of surgical piece, 45 from patients with other parasitic diseases
      and 20 apparently healthy people. The sensitivity, the specificity, positive and
      negative predictive value of immunoblot test, with hidatyd antigen of goat was of
      92.8%, 100%, 100%, 92.8%, respectively, than for ovine antigen was 91.4%, 95.3%,
      95.5%, 91.1%, respectively. Kappa index was 0.93 for goat antigen and 0.86 with
      sheep in relation to the pathological study. We recommended the use of both
      antigens for the serologic diagnosis of human echinococcosis.

PMID- 21072473
TI  - [Marine bacteria producing antibacterial compounds isolated from inter-tidal
      invertebrates].
AB  - Prospective sampling activities of intertidal invertebrates in the Ancon Bay
      (Lima, Peru) were done in order to select marine bacteria producing antimicrobial
      substances. The study included the isolation of bacteria in marine agar, in vitro
      antimicrobial susceptibility testing and electronic microscopic observations. We
      report the isolation, phenotypical characterization and antimicrobial properties
      of 10 strains of marine bacteria including the genus Vibrio, Pseudomonas, and
      Flavobacterium, and the order Actinomycetae that inhibit human pathogens. The
      results indicate that the marine invertebrates would be sources of bacteria
      producing antibiotic substances.

PMID- 21072475
TI  - [Actions and strategies for the prevention and control of road traffic injuries:
      peruvian experience by levels of prevention].
AB  - This article aims to describe the main actions that are being developed in Peru
      for primary and secondary prevention of road traffic injuries, considering the
      epidemiological aspects that characterize the Peruvian experience, as reported in
      other countries. At the primary prevention level, it addresses issues related to
      the timing restriction of the sales of alcoholic beverages, detection of drivers
      with positive testing for alcohol in blood and the chosen driver. Regarding
      secondary prevention, the studies on black spots and the impact containment
      barrels are presented, also a brief overview of the pre-hospital care systems in
      the case of road traffic injuries. There is a need for better characterization of
      the problem, in order to establish healthy public policies regarding traffic
      accidents, there is a need for evidence-based reviews and studies of economic
      evaluations.

PMID- 21072474
TI  - [Effect of levonorgestrel in the ovulation, endometrium, and spermatozoa for
      emergency oral contraception].
AB  - There is wide controversy about the mechanism of action of the levonorgestrel
      used for emergency oral contraception, and many organizations, both scientific as
      well as from the civil society, show their discrepancy with its use, due to its
      possible action as an abortion- inducer. In order to evaluate the scientific
      evidence available on the mechanisms of action of the levonorgestrel used for
      emergency oral contraception (EOC), a systematic revision was performed in the
      Medline and Cochrane library databases. We found 444 articles. After reviewing
      the abstracts, we selected 22 articles, whose complete texts were evaluated. We
      found that the main mechanism of action of the levonorgestrel, given at the doses
      recommended for EOC, is the inhibition or retardation of the ovulation, it
      doesn't affect the spermatozoa in their migration or egg-penetration capacities.
      No morphological or molecular alterations in the endometrium that could interfere
      with the implantation of the fertilized egg have been demonstrated. There is no
      actual scientific evidence available supporting that the use of levonorgestrel
      for EOC is abortive.

PMID- 21072476
TI  - [Tiredness and sleepiness in rural bus drivers during their job performance:
      Peruvian experience and proposals].
AB  - The information indicates that the traffic accidents caused by bus drivers'
      sleepiness or tiredness are frequent in our country. A driver that falls asleep
      while driving cannot perform evasive maneuvers in order to avoid crashes or
      getting off the track, being the result of this kind of accidents a great number
      of victims and infrastructure destruction. In this article we discuss the
      original data published in Peru up to date and make general proposals to face the
      problem.

PMID- 21072477
TI  - [Road traffic injuries in developing countries: research and action agenda].
AB  - Road traffic injury (RTI) is the leading cause of death in persons aged 10-24
      worldwide and accounts for about 15% of all male deaths. The burden of RTI is
      unevenly distributed amongst countries with over eighty-fold differences between
      the highest and lowest death rates. Thus the unequal risk of RTI occurring in the
      developing world, due to many reasons, including but not limited to rapid
      motorization and poor infrastructure, is a major global challenge. This editorial
      highlights a number of key issues that must inform programs designed to prevent
      RTI in the developing world, where the epidemic is all the more insidious.
      Firstly, road safety is a development issue; secondly, road traffic injury is a
      major health issue; thirdly, road traffic injuries can be prevented by the
      implementation of scientific measures; fourth, pre-hospital and hospital
      emergency care is needed; and fifth, research on RTI is neglected in low-income
      and middle-income countries. The repercussion of such progress to Peru is also
      discussed.

PMID- 21072478
TI  - [Reducing pedestrian deaths and injuries due to road traffic injuries in Peru:
      interventions that can work].
AB  - Pedestrians in Peru are the victims of the greatest proportion of road traffic
      fatalities in the world. In 2009, pedestrians were involved in 27% of road
      traffic incidents in Peru. This is a significant public health problem in Peru
      and it has important economic effects as well. We review the evidence for some of
      the solutions and interventions implemented in other countries that may work well
      in Peru to confront this problem via preventing pedestrian-vehicle incidents.
      Most importantly, deploying interventions such as area-wide traffic calming
      through speed bumps, roundabouts, better lighting, one-way streets, detours, and
      blocking some roads has the strongest evidence for reducing injuries and
      fatalities in pedestrians. Other interventions related to education and
      enforcement may have a role as well in very specific contexts, but overall
      designing and modifying the built environment is the most important intervention.

PMID- 21072479
TI  - [Supervising road safety in Peru].
AB  - In this article some problems in road safety are described, which have been
      detected by the Ombudsman of Peru, as part of its role of public administration
      supervisor, amongst these problems we mention: lack of and inadequate elaboration
      of the statistics on road traffic accidents, the inconsistency of the National
      Council for Road Security and the lack of responsibility of the local and
      regional governments reflected by the lack of application of the National Plan of
      Road Safety. Facing this, the Ombudsman suggests that the State develops a
      rigorous statistical system, strengthens the National Council of Road Safety and
      that the different sectors of the government develop the mentioned National Plan.

PMID- 21072480
TI  - [Sleep monitoring in bus and truck drivers: relevant factor to consider for the
      renewal of the driving license].
AB  - The available information indicates that up to one third of the road traffic
      accidents are produced by the driver's sleepiness. Sleep apnea-hypopnea syndrome
      (SAHS) is an organic disease that causes sleepiness. It can be diagnosed by a
      sleep register and can be controlled by different therapeutic means, varying
      their complexity according to its severity, which determines the final cost of
      the management of SAHS. In patients using the therapy thoroughly, the results are
      very good and achieve to control the sleepiness, improve the quality of life of
      the affected subject, protect his health and markedly decrease the risk of
      accidents due to sleepiness during driving. We put into consideration of the
      respective authorities the application of these tests in drivers suspected of
      having SAHS who renew their driving licenses type A-II and A-III.

PMID- 21072481
TI  - [Psychosocial aspects and accidents in land transport].
AB  - Road traffic accidents are a public health problem in Peru, having caused 35 596
      deaths in Peru between 1998 and 2008. Lima is the most affected region,
      presenting 61.7% of the accidents, the annual cost reached one thousand million
      dollars, equivalent to a third part of the investment in health. Available
      studies give emphasis to the protagonists--the drivers, the pedestrians--or to
      equipment and roads; the laws have been modified and containment plans for
      accidents have been implemented, but the incidence remains the same. We raise the
      possibility of exploring behavioral and social factors that could be relevant in
      the genesis of the problem, revising those related to current disorder in
      transport, the behaviors of drivers and pedestrians and the permissiveness of
      society in general particularly of the authority. We propose research and a
      multidisciplinary and intersectoral intervention.

PMID- 21072482
TI  - [Assessment of the structure, dynamics and monitoring of information systems for
      road traffic injuries in Peru--2009].
AB  - OBJECTIVE: A baseline assessment of the structure, dynamics, and monitoring
      capabilities of the information systems for road traffic injuries was conducted
      in three Peruvian cities: Lima, Huamanga and Pucallpa. MATERIAL AND METHODS: 50
      in-depth interviews were performed with key stakeholders, including managers and
      operators of information systems. The instrument was developed taking into
      account international standards and recommendations for information systems.
      RESULTS: Six information systems were identified, some of which contain
      integrated operational systems enabling the recollection, processing, aggregation
      and data analysis following automated processes. These systems are considered
      valuable by different stakeholders because of their ability to present data in an
      organized manner. A low level of collaboration and exchange of information
      between institutions in the diverse aspects of data collection, processing and
      usage was observed. Officially, formal collaboration agreements between
      institutions do exist, potentially enabling more collaborative work. An interest
      was expressed in establishing an integrated information system due to the need
      for detailed and solid/trusted information that maximizes the use of existing
      resources. CONCLUSIONS: Current information systems for road traffic injuries
      have limitations. The actual use and utility of the information for decision
      making for prevention of road traffic injuries nationwide is limited.

PMID- 21072483
TI  - [Ethnolinguistic map of Peru].
AB  - To provide adequate health care with an intercultural approach is necessary for
      the health care personnel know the Peruvian ethnolinguistic diversity, so we
      present 76 ethnic groups that belong to 16 ethnolinguistic families and their
      geographical distribution on a map of Peru.

PMID- 21072484
TI  - [Guillain Barre syndrome in association with Brucellosis].
AB  - We describe a case of a 47 years old male, with a history of 2 days of
      progressive, ascendant, symmetrical weakness in the lower extremities; a lumbar
      puncture was performed after the brain CT scan, as well as an electromyography,
      evidencing pure motor polyradiculopathy with axonal pattern, compatible with
      Guillain Barre syndrome. Afterwards, he received four plasmapheresis sessions,
      with clinical improvement from the second session. Due to his epidemiological
      background, Brucella set testing was done. Rose Bengal was positive, antibiotic
      treatment with rifampin and doxicicline was initiated, as well as rehabilitation.
      Three months later the patient recovered completely. The relevance of early
      treatment with plasmapheresis and the definition of the etiologic diagnosis
      determine that the prognosis of the Guillain Barre syndrome is favorable.

PMID- 21072485
TI  - [Arturo Vasi Paez (1924-2008)].

PMID- 21072486
TI  - [Indigenous populations from Peru].

PMID- 21072487
TI  - [Tuberculosis in indigenous people].

PMID- 21072488
TI  - [Latent tuberculosis: chemoprophylactic coverage of household contacts in Peru].

PMID- 21072490
TI  - [About interculturality].

PMID- 21072491
TI  - [Undergraduate students: the future of research].

PMID- 21072492
TI  - Suppression of vascular smooth muscle cell responses induced by TNF-alpha in GM3
      synthase gene transfected cells.
AB  - The natural accumulation of ganglioside GM3 (N-glycolylneuraminic acid) on
      atherosclerotic lesions is a common theory. The present study is the first to
      examine the effects of the GM3 synthase gene on the responses of vascular smooth
      muscle cells (VSMC) to tumor necrosis factor-alpha (TNF-alpha). We found that
      overexpression of the GM3 synthase gene inhibited DNA synthesis and ERK1/2
      activity induced by TNF-alpha in VSMC, whereas the basal levels of DNA synthesis
      and ERK1/2 activity remained unchanged. In addition, GM3 synthase gene
      transfectants significantly reduced the migration and invasion of VSMC following
      TNF-alpha treatment, compared with empty vector transfectants. Furthermore, TNF
      alpha-induced matrix metalloproteinase-9 (MMP-9) expression and promoter activity
      were also decreased in GM3 synthase gene transfectants. GM3 synthase gene
      expression markedly suppressed the TNF-alpha-stimulated transcriptional activity
      of activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), which are
      the controlling factors of MMP-9 expression. Consistent with these results, the
      addition of anti-GM3 antibody into the GM3 synthase gene transfectants blocked
      inhibition of DNA synthesis, ERK1/2 activity, migration and invasion. Finally,
      GM3 synthase gene transfectants treated with anti-GM3 antibody reversed the
      suppression of MMP-9 expression by reducing AP-1 and NF-kappaB binding activity.
      These results suggest regulatory roles for the GM3 synthase gene in VSMC
      proliferation and migration during the formation of atherosclerotic lesions.

PMID- 21072493
TI  - Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by
      suppressing NF-kappaB activation.
AB  - Several bone protective factors are reported to exhibit stimulatory activities on
      bone formation coupled with inhibitory effects on bone resorption; one such
      factor is vitamin K2. Vitamin K species [K1 (phylloquinone) and K2 (menaquinone)]
      have long been associated with bone protective activities and are receiving
      intense interest as nutritional supplements for the prevention or amelioration of
      bone disease in humans. However, the mechanisms of vitamin K action on the
      skeleton are poorly defined. Activation of the nuclear factor kappaB (NF-kappaB)
      signal transduction pathway is essential for osteoclast formation and resorption.
      By contrast, NF-kappaB signaling potently antagonizes osteoblast differentiation
      and function, prompting us to speculate that NF-kappaB antagonists may represent
      a novel class of dual anti-catabolic and pro-anabolic agents. We now show that
      vitamin K2 action on osteoblast and osteoclast formation and activity is
      accomplished by down-regulating basal and cytokine-induced NF-kappaB activation,
      by increasing IkappaB mRNA, in a gamma-carboxylation-independent manner.
      Furthermore, vitamin K2 prevented repression by tumor necrosis factor alpha
      (TNFalpha) of SMAD signaling induced by either transforming growth factor beta
      (TGFbeta) or bone morphogenetic protein-2 (BMP-2). Vitamin K2 further antagonized
      receptor activator of NF-kappaB (RANK) ligand (RANKL)-induced NF-kappaB
      activation in osteoclast precursors. Our data provide a novel mechanism to
      explain the dual pro-anabolic and anti-catabolic activities of vitamin K2, and
      may further support the concept that pharmacological modulation of NF-kappaB
      signal transduction may constitute an effective mechanism for ameliorating
      pathological bone loss and for promoting bone health.

PMID- 21072494
TI  - Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies.
AB  - Among the different processes occurring during the evolution of liver disease,
      fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant
      irrespective of the underlying etiology. Cirrhosis is the end-stage of this
      reaction. Metabolic profiles, which are affected by many physiological and
      pathological processes, may provide further insight into the metabolic
      consequences of this severe liver disease. The aim of this study was to
      demonstrate the applicability of 1H high resolution magic angle spinning (HR-MAS)
      NMR spectroscopy in the biochemical profile determination of human liver needle
      biopsy samples for the characterization of metabolic alterations related to the
      severity of liver disease. We recorded and analyzed HR-MAS spectra of 68 liver
      tissue samples obtained by needle biopsy from patients with chronic liver
      disease. Multivariate analysis was applied to these data to obtain discrimination
      patterns and to reveal relevant metabolites. The metabolic characterization of
      liver tissue from needle biopsies by HR-MAS NMR spectroscopy provided
      differential patterns for cirrhotic and non-cirrhotic chronic liver disease
      tissue. Metabolites closely related to the liver metabolism such as some fatty
      acids, glucose and amino acids show differences between the two groups.
      Phospholipid precursors, which have been previously correlated with hepatic
      lesions also show differences. Furthermore, the correlation between
      histologically assessed liver disease stages and the levels of the most
      discriminative metabolites show that liver dysfunction is present at the initial
      stages of chronic hepatic lesions. Overall, this work suggests that the
      additional information obtained by NMR metabolomics applied to needle biopsies of
      human liver may be useful for assessing metabolic alterations and liver
      dysfunction in chronic liver disease.

PMID- 21072495
TI  - [Diminishing borders between cardiology and cardiothoracic surgery: quo vadis?].
AB  - Increasingly complex techniques in cardiovascular medicine lead to a competitive
      partnership between cardiology and cardiac surgery. Common challenges will arise
      in the fields of coronary heart disease, heart valves, heart failure and rhythm
      therapy. For instance, coronary revascularization in acute myocardial infarction
      is no longer considered to exclusively be an interventional option. In
      comparison, the implantation of heart valves is increasingly carried out by
      cardiologists using interventional techniques. The latest designs of sutureless
      valves try to combine the benefits of conventional and transcatheter heart
      valves. Heart failure is the most common reason for hospital admission and thus
      an important therapeutic target for cardiology and cardiac surgery. New
      approaches in diagnostics, heart assist devices and cellular therapy meet this
      challenge. CONCLUSION: In the future only a sensitive and transparent
      collaboration across transsectoral borders will offer optimal therapy in
      cardiovascular medicine.

PMID- 21072496
TI  - Cross-cultural and cross-ecotype production of a killer whale 'excitement' call
      suggests universality.
AB  - Facial and vocal expressions of emotion have been found in a number of social
      mammal species and are thought to have evolved to aid social communication. There
      has been much debate about whether such signals are culturally inherited or are
      truly biologically innate. Evidence for the innateness of such signals can come
      from cross-cultural studies. Previous studies have identified a vocalisation (the
      V4 or 'excitement' call) associated with high arousal behaviours in a population
      of killer whales in British Columbia, Canada. In this study, we compared
      recordings from three different socially and reproductively isolated ecotypes of
      killer whales, including five vocal clans of one ecotype, each clan having
      discrete culturally transmitted vocal traditions. The V4 call was found in
      recordings of each ecotype and each vocal clan. Nine independent observers
      reproduced our classification of the V4 call from each population with high inter
      observer agreement. Our results suggest the V4 call may be universal in Pacific
      killer whale populations and that transmission of this call is independent of
      cultural tradition or ecotype. We argue that such universality is more consistent
      with an innate vocalisation than one acquired through social learning and may be
      linked to its apparent function of motivational expression.

PMID- 21072497
TI  - Lead concentration distribution and source tracing of urban/suburban aquatic
      sediments in two typical famous tourist cities: Haikou and Sanya, China.
AB  - The content and spatial distribution of lead in the aquatic systems in two
      Chinese tropical cities in Hainan province (Haikou and Sanyan) show an unequal
      distribution of lead between the urban and the suburban areas. The lead content
      is significantly higher (72.3 mg/kg) in the urban area than the suburbs (15.0
      mg/kg) in Haikou, but quite equal in Sanya (41.6 and 43.9 mg/kg). The frequency
      distribution histograms suggest that the lead in Haikou and in Sanya derives from
      different natural and/or anthropogenic sources. The isotopic compositions
      indicate that urban sediment lead in Haikou originates mainly from anthropogenic
      sources (automobile exhaust, atmospheric deposition, etc.) which contribute much
      more than the natural sources, while natural lead (basalt and sea sands) is still
      dominant in the suburban areas in Haikou. In Sanya, the primary source is natural
      (soils and sea sands).

PMID- 21072498
TI  - Cerebrospinal fluid pentraxin 3 early after subarachnoid hemorrhage is associated
      with vasospasm.
AB  - PURPOSE: To investigate plasma and cerebrospinal fluid (CSF) concentrations of
      pentraxin 3 (PTX3), a prototypic long pentraxin protein induced by
      proinflammatory signals, in subarachnoid hemorrhage (SAH), and its relation with
      SAH-associated vasospasm. METHODS: Serial plasma and CSF samples were collected
      from 38 consecutive SAH patients admitted to the Neurosurgical Intensive Care.
      PTX3 concentrations were analyzed in relation to clinical status and clinical
      vasospasm (defined as neuro-worsening and angiographic confirmation of vessel
      narrowing). Since neutrophils are an important source of preformed PTX3,
      myeloperoxidase (MPO) in CSF was measured to assess the correlation with CSF PTX3
      and establish whether blood contamination was the determinant of PTX3 increase.
      RESULTS: PTX3 was elevated in all SAH patients both in plasma and CSF. Acute peak
      (first 48 h after SAH) CSF PTX3 was significantly higher in patients who later
      developed vasospasm [median 13.6 (range 2.3-51.9) ng/ml] compared to those who
      did not [3.2 (0.1-50.5) ng/ml, p = 0.03]. The temporal pattern of CSF PTX3 in
      patients with vasospasm was triphasic with a peak during the first 48 h after
      SAH, a subsequent decrease in the following 48-96 h and a secondary significant
      increase with the occurrence of vasospasm. A loose correlation between CSF PTX3
      and MPO was observed (r(2) = 0.13), indicating that following SAH there is a
      brain production of PTX3. CONCLUSIONS: Acute increased concentrations of PTX3 in
      CSF but not in plasma are related to the occurrence of vasospasm, indicating that
      measurement of CSF PTX3 associated with the clinical evaluation can improve early
      diagnosis of this complication.

PMID- 21072500
TI  - Outcome of tension-free obturator tape procedures in obese and overweight women.
AB  - INTRODUCTION AND HYPOTHESIS: Little data are available on the outcome of tension
      free obturator tape (TVT-O) procedures in obese and overweight women. We
      hypothesized that the subjective and objective outcomes of TVT-O in women with a
      higher body mass index (BMI) would differ from those with a lower BMI. METHODS:
      We retrospectively reviewed the records of 129 patients who had undergone TVT-O,
      stratifying by BMI into normal weight (n = 39), overweight (n = 58), and obese (n
      = 32) groups. We compared pre- and postoperative evaluations, including
      subjective and objective outcome of TVT-O, complications, and quality of life
      assessed by validated questionnaires. RESULTS: The median follow-up was 24
      months. There were no significant differences between groups in terms of
      objective cure rate and subjective success, quality of life scores, or
      postoperative complications. CONCLUSION: BMI did not influence the outcome of TVT
      O procedures at a median of 24 months after surgery.

PMID- 21072499
TI  - Long pentraxin PTX3 deficiency worsens LPS-induced acute lung injury.
AB  - OBJECTIVE: Long pentraxin PTX3 is an inflammatory mediator and a component of the
      humoral arm of innate immunity. PTX3 expression is increased in animals with
      acute lung injury (ALI) and in patients with sepsis or acute respiratory distress
      syndrome and is considered to be a potential biomarker for these diseases.
      However, the role of PTX3 in the pathogenesis of ALI is not fully understood. We
      hypothesized that PTX3, as an important immune modulator, may determine the
      severity of ALI. METHODS: Lipopolysaccharide (LPS) was intra-tracheally
      administrated to PTX3 knock-out (PTX3-KO) and wild-type (WT) mice. Lung injury,
      neutrophil infiltration, cell death, fibrin deposition, and tissue factor
      expression in the lung were determined. Local and systemic inflammatory responses
      were assessed by measuring cytokines in the lung and plasma. RESULTS: LPS
      instillation induced ALI in both PTX3-KO and WT mice. Interestingly, PTX3
      deficiency significantly increased the magnitude/extent of lung injury compared
      to that in WT mice. The severe lung injury was accompanied by elevated neutrophil
      infiltration, cell death, and fibrin deposition in the lung. PTX3 deficiency also
      enhanced LPS-induced tissue factor expression/activation in the lung and
      increased tumor necrosis factor-alpha and monocyte chemoattractant protein-1
      levels in the plasma. CONCLUSION: Our data suggest that the endogenously
      expressed PTX3 plays a protective role in the pathogenesis of ALI and that a lack
      of PTX3 may enhance neutrophil recruitment, cell death, activation of coagulation
      cascades, and inflammatory responses in the lung.

PMID- 21072501
TI  - Risk for antipsychotic-induced extrapyramidal symptoms: influence of family
      history and genetic susceptibility.
AB  - OBJECTIVES: This study aims to further evaluate the impact of family history of
      primary movement disorders (FHpMD) and a candidate genetic variant on risk of
      antipsychotic-induced extrapyramidal symptoms (EPS). METHODS: We examined 156 (76
      men) inpatients receiving antipsychotics for EPS and FHpMD stratified by patient
      characteristics. The genetic analysis included genotyping of a multiallelic
      dinucleotide polymorphism in the ATP1A3 gene. RESULTS: EPS lifetime prevalence
      was 69% and more frequent in the presence of FHpMD (p = 0.052), particularly in
      patients younger than 60 years (p = 0.012) and with acute dystonic reactions. The
      ATP1A3 polymorphism showed an allele length-dependent association with
      parkinsonism (p=0.019 uncorrected, p=0.057 corrected) exclusively. Carriers of
      the shortest allele had a 7.7-fold increased risk for parkinsonism. CONCLUSIONS:
      The association of FHpMD and EPS may be linked to the EPS subtype and age of the
      patient. A common ATP1A3 genomic variation may represent a susceptibility factor
      for the risk for antipsychotic-induced parkinsonism in an allele-dependent
      manner.

PMID- 21072502
TI  - Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and
      clinical issues.
AB  - BACKGROUND: Recently, those substances deriving from the active ingredient of the
      Khat plant, cathinone, have been rising in popularity. Indeed, 4
      methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as
      a cheaper alternative to other classified recreational drugs. AIMS: We aimed here
      at providing a state-of-the-art review on mephedrone history and prevalence of
      misuse, chemistry, pharmacology, legal status, product market appearance,
      clinical/management and related fatalities. METHODS: Because of the limited
      evidence, some of the information here presented has been obtained from user
      reports/drug user-orientated web sites. The most common routes for mephedrone
      recreational use include insufflation and oral ingestion. It elicits stimulant
      and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and
      MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a
      number of both physical and psychopathological side effects. Recent preliminary
      analysis of recent UK data carried out in 48 related cases have provided positive
      results for the presence of mephedrone at postmortem. DISCUSSION AND CONCLUSIONS:
      Within the UK, diffusion of mephedrone may have been associated with an
      unprecedented combination of a particularly aggressive online marketing policy
      and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has
      been recently classified in both the UK and in a number of other countries as a
      measure to control its availability. Following this, a few other research
      psychoactives have recently entered the online market as yet unregulated
      substances that may substitute for mephedrone. Only international collaborative
      efforts may be able to tackle the phenomenon of the regular offer of novel
      psychoactive drugs.

PMID- 21072503
TI  - Subjective and physiological effects of acute intranasal methamphetamine during d
      amphetamine maintenance.
AB  - RATIONALE: Methamphetamine abuse and dependence are significant public-health
      concerns. Behavioral therapies are effective for reducing methamphetamine use.
      However, many patients enrolled in behavioral therapies are unable to achieve
      significant periods of abstinence, suggesting other strategies like
      pharmacotherapy are needed. OBJECTIVES: This experiment determined the subjective
      and physiological effects of intranasal methamphetamine during D: -amphetamine
      maintenance in eight non-treatment-seeking stimulant-dependent participants. We
      predicted D: -amphetamine maintenance would attenuate the acute subjective
      effects of intranasal methamphetamine. We also predicted intranasal
      methamphetamine would be well tolerated during D: -amphetamine maintenance.
      METHODS: After at least 7 days of maintenance on sustained-release D: 
      amphetamine (0 and 45 mg/day), participants were administered ascending doses of
      intranasal methamphetamine (0, 2.5, 5, 10, and 20 mg) across two experimental
      sessions. Intranasal methamphetamine doses were separated by 90 min. RESULTS:
      Intranasal methamphetamine produced prototypical subjective and physiological
      effects (e.g., increased ratings of Like Drug; increased heart rate, blood
      pressure, and body temperature). The acute effects of intranasal methamphetamine
      were significantly diminished during D: -amphetamine maintenance relative to
      placebo maintenance. CONCLUSIONS: These results are concordant with those of
      clinical trials and provide further support for the use of agonist replacement
      therapy to manage methamphetamine dependence. Additional research in humans is
      needed to determine the effectiveness of D: -amphetamine under different
      experimental conditions that more closely reflect use in the natural environment
      (e.g., higher methamphetamine doses) and behavioral arrangements that are
      predictive of pharmacotherapy effectiveness (e.g., drug self-administration).

PMID- 21072504
TI  - Loudness dependence of auditory evoked potentials (LDAEP) correlates with the
      availability of dopamine transporters and serotonin transporters in healthy
      volunteers-a two isotopes SPECT study.
AB  - RATIONALE AND OBJECTIVE: Although loudness dependence of auditory evoked
      potentials (LDAEPs) had been suggested as a noninvasive measure of central
      serotonin functions, recent studies suggest that LDAEP may be modulated by
      multiple neuromodulatory systems, such as dopamine. Here, we explore the
      relationship between LDAEP and dopamine and serotonin in the level of monoamine
      transporter availability. METHODS: Forty-nine healthy volunteers received LDAEP
      and single-photon emission computed tomography (SPECT) using [(99m)Tc] TRODAT and
      [(123)I] ADAM to approximate the availability of dopamine transporters (DATs) and
      serotonin transporters (SERTs). RESULTS: LDAEP was found to be positively
      associated with DAT, after adjusting for age and gender, and the log-transformed
      slope of loudness dependence at Cz was negatively associated with SERT.
      CONCLUSION: Our findings provide further evidence for the possible involvement of
      dopamine and serotonins in the genesis of LDAEP.

PMID- 21072505
TI  - Authentication of fattening diet of Iberian pigs according to their volatile
      compounds profile from raw subcutaneous fat.
AB  - The composition of volatile components of subcutaneous fat from Iberian pig has
      been studied. Purge and trap gas chromatography-mass spectrometry has been used.
      The composition of the volatile fraction of subcutaneous fat has been used for
      authentication purposes of different types of Iberian pig fat. Three types of
      this product have been considered, montanera, extensive cebo and intensive cebo.
      With classification purposes, several pattern recognition techniques have been
      applied. In order to find out possible tendencies in the sample distribution as
      well as the discriminant power of the variables, principal component analysis was
      applied as visualisation technique. Linear discriminant analysis (LDA) and soft
      independent modelling by class analogy (SIMCA) were used to obtain suitable
      classification models. LDA and SIMCA allowed the differentiation of three
      fattening diets by using the contents in 2,2,4,6,6-pentamethyl-heptane, m-xylene,
      2,4-dimethyl-heptane, 6-methyl-tridecane, 1-methoxy-2-propanol, isopropyl
      alcohol, o-xylene, 3-ethyl-2,2-dimethyl-oxirane, 2,6-dimethyl-undecane, 3-methyl
      3-pentanol and limonene.

PMID- 21072506
TI  - Calibration and uncertainty assessment for certified reference gas mixtures.
AB  - The weighted least squares method to build an analysis function described in ISO
      6143, Gas analysis--Comparison methods for determining and checking the
      composition of calibration gas mixtures, is modified to take into account the
      typically small number of instrumental readings that are obtained for each
      primary standard gas mixture used in calibration. The theoretical basis for this
      modification is explained, and its superior performance is illustrated in a
      simulation study built around a concrete example, using real data. The
      corresponding uncertainty assessment is obtained by application of a Monte Carlo
      method consistent with the guidance in the Supplement 1 to the Guide to the
      expression of uncertainty in measurement, which avoids the need for two
      successive applications of the linearizing approximation of the conventional
      method for uncertainty propagation. The three main steps that NIST currently uses
      to certify a reference gas mixture (homogeneity study, calibration, and
      assignment of value and uncertainty assessment), are described and illustrated
      using data pertaining to an actual standard reference material.

PMID- 21072507
TI  - Transplacental passage of the non-ionic contrast agent iopamidol in twins.
AB  - Premature dizygotic twins, exposed in utero to iopamidol (Isovue-370(r)) 4 days
      prior to delivery, were born with abdominal radiopaque densities that made
      exclusion of necrotizing enterocolitis difficult when they developed abdominal
      distention and feeding intolerance. This is a unique case report of
      transplacental passage of iopamidol.

PMID- 21072508
TI  - Steered molecular dynamics simulations of ligand-receptor interaction in
      lipocalins.
AB  - Retinol binding protein (RBP) and an engineered lipocalin, DigA16, have been
      studied using molecular dynamics simulations. Special emphasis has been placed on
      explaining the ligand-receptor interaction in RBP-retinol and DigA16-digoxigenin
      complexes, and steered molecular dynamics simulations of 10-20 ns have been
      carried out for the ligand expulsion process. Digoxigenin is bound deep inside
      the cavity of DigA16 and forms several stable hydrogen bonds in addition to the
      hydrophobic van der Waals interaction with the aromatic side-chains. Four
      crystalline water molecules inside the ligand-binding cavity remain trapped
      during the simulations. The strongly hydrophobic receptor site of RBP differs
      considerably from DigA16, and the main source of ligand attraction comes from the
      phenyl side-chains. The hydrogen bonds between digoxigenin and DigA16 cause the
      rupture forces on ligand removal in DigA16 and RBP to differ. The mutated DigA16
      residues contribute approximately one-half of the digoxigenin interaction energy
      with DigA16 and, of these, the energetically most important are residues His35,
      Arg58, Ser87, Tyr88, and Phe114. Potential "sensor loops" were found for both
      receptors. These are the outlier loops between residues 114-121 and 63-67 for
      DigA16 and RBP, respectively, and they are located near the entrance of the
      ligand-binding cavity. Especially, the residues Glu119 (DigA16) and Leu64 (RBP)
      are critical for sensing. The ligand binding energies have been estimated based
      on the linear response approximation of binding affinity by using a previous
      parametrization for retinoids and RBP.

PMID- 21072509
TI  - Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis
      C.
AB  - Host genetic variation may affect the outcome of chronic viral hepatitides,
      favoring viral clearance and/or modulating the inflammatory response to
      persistent infection. Our aims were to assess whether interleukin 6 (IL-6)
      promoter polymorphisms are associated with chronic hepatitis C virus (HCV)
      infection and to clarify the role of IL-6 haplotypes in facilitating progressive
      disease. The study included 424 Italian patients (233 males, median age 53 years)
      affected by HCV chronic infection. IL6 -1363, -597, -572, -174, and +2954
      polymorphic loci were assayed by means of restriction fragment length
      polymorphism. Three hundred forty-four healthy Italian blood donors (245 males,
      median age 50 years) served as controls. Comparing patients and controls analysis
      of molecular variance was highly significant (p < 0.0001); at a locus by locus
      approach, the frequencies of minor alleles in the -1363 (p < 0.02), -597 (p <
      0.02), and -174 (p < 0.01) polymorphisms were confirmed to be less represented in
      patients than in controls. Carrying the wild-type G allele at the -597 and -174
      loci identified an unfavorable haplotype; carrying the minor allele in one/both
      loci identified an indifferent/favorable haplotype. Male patients carrying two
      unfavorable haplotypes had the highest adjusted mean +/- standard error Ishak
      staging score (3.56 +/- 0.19), while females carrying one or no unfavorable
      haplotypes had the lowest (2.69 +/- 0.21); the remaining patients had an
      intermediate value (3.12 +/- 0.13, p < 0.01). In conclusion, IL-6 promoter
      polymorphisms influence the development of chronic HCV infection. With the
      permissive effect of male gender, haplotypes represented by the wild-type allele
      for -597 and -174 loci appear to favor a worse evolution of the disease.

PMID- 21072510
TI  - Early monitoring of response to neoadjuvant chemotherapy in breast cancer with
      18F-FDG PET/CT: defining a clinical aim.

PMID- 21072511
TI  - Molecular imaging of sigma receptors: synthesis and evaluation of the potent
      sigma1 selective radioligand [18F]fluspidine.
AB  - PURPOSE: Neuroimaging of sigma(1) receptors in the human brain has been proposed
      for the investigation of the pathophysiology of neurodegenerative and psychiatric
      diseases. However, there is a lack of suitable (18)F-labelled PET radioligands
      for that purpose. METHODS: The selective sigma(1) receptor ligand
      [(18)F]fluspidine (1'-benzyl-3-(2-[(18)F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'
      piperidine]) was synthesized by nucleophilic (18)F(-) substitution of the tosyl
      precursor. In vitro receptor binding affinity and selectivity were assessed by
      radioligand competition in tissue homogenate and autoradiographic approaches. In
      female CD-1 mice, in vivo properties of [(18)F]fluspidine were evaluated by ex
      vivo brain section imaging and organ distribution of intravenously administered
      radiotracer. Target specificity was validated by organ distribution of
      [(18)F]fluspidine after treatment with 1 mg/kg i.p. of the sigma receptor
      antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen.
      In vitro metabolic stability and in vivo metabolism were investigated by LC-MS(n)
      and radio-HPLC analysis. RESULTS: [(18)F]Fluspidine was obtained with a
      radiochemical yield of 35-45%, a radiochemical purity of >= 99.6% and a specific
      activity of 150-350 GBq/MUmol (n = 6) within a total synthesis time of 90-120
      min. In vitro, fluspidine bound specifically and with high affinity to sigma(1)
      receptors (K (i) = 0.59 nM). In mice, [(18)F]fluspidine rapidly accumulated in
      brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and
      13 at 5 and 30 min after intravenous application of the radiotracer,
      respectively. By ex vivo autoradiography of brain slices, resemblance between
      binding site occupancy of [(18)F]fluspidine and the expression of sigma(1)
      receptors was shown. The radiotracer uptake in the brain as well as in peripheral
      sigma(1) receptor expressing organs was significantly inhibited by haloperidol
      but not by tamoxifen. Incubation with rat liver microsomes led to a fast
      biotransformation of fluspidine. After an incubation period of 30 min only 13% of
      the parent compound was left. Seven metabolites were identified by HPLC-UV and LC
      MS(n) techniques. However, [(18)F]fluspidine showed a higher metabolic stability
      in vivo. In plasma samples ~ 94% of parent compound remained at 30 min and ~ 67%
      at 60 min post-injection. Only one major radiometabolite was detected. None of
      the radiometabolites crossed the blood-brain barrier. CONCLUSION:
      [(18)F]Fluspidine demonstrated favourable target affinity and specificity as well
      as metabolic stability both in vitro and in animal experiments. The in vivo
      properties of [(18)F]fluspidine offer a high potential of this radiotracer for
      neuroimaging and quantitation of sigma(1) receptors in vivo.

PMID- 21072512
TI  - Correlation of biological aggressiveness assessed by 11C-methionine PET and
      hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed
      glioblastoma.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is characterized by tissue hypoxia
      associated with resistance to radiotherapy and chemotherapy. To clarify the
      biological link between hypoxia and tumour-induced neovascularization and tumour
      aggressiveness, we analysed detailed volumetric and spatial information of viable
      hypoxic tissue assessed by (18)F-fluoromisonidazole (FMISO) PET relative to
      neovascularization in Gd-enhanced MRI and tumour aggressiveness by L-methyl-(11)C
      methionine (MET) PET in newly diagnosed GBMs. METHODS: Ten patients with newly
      diagnosed GBMs were investigated with FMISO PET, MET PET and Gd-enhanced MRI
      before surgery. Tumour volumes were calculated by performing a three-dimensional
      threshold-based volume of interest (VOI) analysis for metabolically active volume
      on MET PET (MET uptake indices of >=1.3 and >=1.5) and Gd-enhanced volume on MRI.
      FMISO PET was scaled to the blood FMISO activity to create tumour to blood (T/B)
      images. The hypoxic volume (HV) was defined as the region with T/B greater than
      1.2. PET and MR images of each patient were coregistered to analyse the spatial
      location of viable hypoxic tissue relative to neovascularization and active
      tumour extension. RESULTS: Metabolically active tumour volumes defined using MET
      uptake indices of >=1.3 and >=1.5 and the volumes of Gd enhancement showed a
      strong correlation (r = 0.86, p < 0.01 for an index of >=1.3 and r = 0.77, p <
      0.05 for an index of >=1.5). The HVs were also excellently correlated with the
      volumes of Gd enhancement (r = 0.94, p < 0.01). The metabolically active tumour
      volumes as defined by a MET uptake index of >=1.3 and the HVs exhibited a strong
      correlation (r = 0.87, p < 0.01). On superimposed images, the metabolically
      active area on MET PET defined by a MET uptake index of >=1.3 was usually larger
      than the area of the Gd enhancement and about 20-30% of the MET area extended
      outside the area of the enhancement. On the other hand, the surface area of
      viable hypoxic tissue with a T/B cutoff of >=1.2 on FMISO PET did not
      substantially differ from the area of the Gd enhancement. CONCLUSION: The
      volumetric analysis demonstrates that the viable hypoxic tissue assessed by FMISO
      PET is related to the neovascularization in Gd-enhanced MRI and the tumour
      aggressiveness by MET PET in newly diagnosed GBMs. The spatial analysis shows
      that the metabolically active tumour may be substantially underestimated by Gd
      enhanced MRI. Complementary use of MET and FMISO to Gd-enhanced MRI may improve
      the understanding of tumour biology and lead to the most efficient delineation of
      tumour volume and treatment strategy.

PMID- 21072513
TI  - 177Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable
      effectiveness to 213Bi-immunotherapy, but causes toxicity not observed with
      213Bi.
AB  - PURPOSE: (213)Bi-d9MAb-immunoconjugates targeting gastric cancer cells have
      effectively cured peritoneal carcinomatosis in a nude mouse model following
      intraperitoneal injection. Because the beta-emitter (177)Lu has proven to be
      beneficial in targeted therapy, (177)Lu-d9MAb was investigated in this study in
      order to compare its therapeutic efficacy and toxicity with those of (213)Bi
      d9MAb. METHODS: Nude mice were inoculated intraperitoneally with HSC45-M2 gastric
      cancer cells expressing d9-E-cadherin and were treated intraperitoneally 1 or 8
      days later with different activities of specific (177)Lu-d9MAb immunoconjugates
      targeting d9-E-cadherin or with nonspecific (177)Lu-d8MAb. Therapeutic efficacy
      was evaluated by monitoring survival for up to 250 days. For evaluation of
      toxicity, both biodistribution of (177)Lu-d9MAb and blood cell counts were
      determined at different time points and organs were examined histopathologically.
      RESULTS: Treatment with (177)Lu-immunoconjugates (1.85, 7.4, 14.8 MBq)
      significantly prolonged survival. As expected, treatment on day 1 after tumour
      cell inoculation was more effective than treatment on day 8, and specific (177)Lu
      d9MAb conjugates were superior to nonspecific (177)Lu-d8MAb. Treatment with 7.4
      MBq of (177)Lu-d9MAb was most successful, with 90% of the animals surviving
      longer than 250 days. However, treatment with therapeutically effective
      activities of (177)Lu-d9MAb was not free of toxic side effects. In some animals
      lymphoblastic lymphoma, proliferative glomerulonephritis and hepatocarcinoma were
      seen but were not observed after treatment with (213)Bi-d9MAb at comparable
      therapeutic efficacy. CONCLUSION: The therapeutic efficacy of (177)Lu-d9MAb
      conjugates in peritoneal carcinomatosis is impaired by toxic side effects.
      Because previous therapy with (213)Bi-d9MAb revealed comparable therapeutic
      efficacy without toxicity it should be preferred for the treatment of peritoneal
      carcinomatosis.

PMID- 21072514
TI  - Question mark ear deformity: a combined method for correction.
AB  - Question mark ear deformity or Cosman ear is a very uncommon congenital
      alteration. The deformity includes a cleft between the posterior helix and the
      lobule, an increase in anterior projection, an abnormal superior third that
      modifies the superior crura and the scaphoid fossa, partial or complete absence
      of the antihelix, transposition of the lobule and antihelix (severe cases), and
      postauricular tags. The authors present a case of moderate question mark ear
      deformity treated using Mustarde sutures and two cartilage grafts to correct the
      support and the contour defect. Adequate correction of the deformity and symmetry
      was achieved for both ears. The technique described in this report is suitable
      for minimal to moderate defects.

PMID- 21072515
TI  - Surgical correction of gynecomastia in thin patients.
AB  - BACKGROUND: Gynecomastia refers to a benign enlargement of the male breast. This
      article describes the authors' method of using power-assisted liposuction and
      gland removal through a subareolar incision for thin patients. METHODS: Power
      assisted liposuction is performed for removal of fatty breast tissue in the chest
      area to allow skin retraction. The subareolar incision is used to remove
      glandular tissue from a male subject considered to be within a normal weight
      range but who has bilateral grade 1 or 2 gynecomastia. RESULTS: Gynecomastia
      correction was successfully performed for all the patients. The average volume of
      aspirated fat breast was 100-200 ml on each side. Each breast had 5-80 g of
      breast tissue removed. At the 3-month, 6-month, and 1-year follow-up assessments,
      all the treated patients were satisfied with their aesthetic results.
      CONCLUSIONS: Liposuction has the advantages of reducing the fat tissue where
      necessary to allow skin retraction and of reducing the traces left by surgery.
      The combination of surgical excision and power-assisted lipoplasty also is a
      valid choice for the treatment of thin patients.

PMID- 21072516
TI  - Late hematoma, seroma, and galactocele in breasts injected with polyacrylamide
      gel.
AB  - Late hematoma or seroma and galactocele caused by augmentation mammaplasty have
      been reported in patients with silicon breast prostheses but are extremely rare
      in patients injected with polyacrylamide gel (PAAG). In a retrospective survey,
      the incidence, clinical manifestations, and management of late hematoma, seroma,
      and galactocele in 28 of 2,610 patients who underwent breast augmentation with
      PAAG injection were investigated, and 5 typical cases are presented. The
      diagnostic and managing methods for this complication have been assessed. The
      incidence of late hematoma or seroma was 0.65% and that of galactocele was 0.35%
      among patients with PAAG-injected breast augmentations. The clinical onsets of
      such late PAAG complications were of two types: rapid enlargement in 17 patients
      and progressive expansion in another 11 patients. Aspiration, ultrasound, and
      magnetic resonance imaging (MRI) are useful and sensitive tools for diagnosis.
      Foreign body reaction, PAAG-related tissue necrosis and fibrosis, and granuloma
      were shown, and the bacterial cultures in all 12 cases were negative. Needle
      aspiration with pressure dressing has been advocated as a reliable method for
      small diseases, and surgical exploration with irrigation-vacuum drainage and
      evacuation with capsulectomy have been considered more effective for recurrent,
      large, and long-term cases. In conclusion, these late complications rarely
      present after large-volume injections of PAAG for breast augmentation. The PAAG
      related pathologic inflammatory tissue changes are suggested as the pathogenesis
      for the complication. Trauma and breastfeeding are considered to be stimulating
      factors.

PMID- 21072517
TI  - Genotyping of intron 22-related rearrangements of F8 by inverse-shifting PCR in
      Egyptian hemophilia A patients.
AB  - Hemophilia A (HA) is the most common severe bleeding disorder in humans,
      affecting one in 5,000 male births. In severe HA, intron 22 inversion of F8 is
      the most prevalent mutation, accounting for 40-50% of all mutations; however,
      little is known about the disease-causing mutations among Egyptian hemophiliacs.
      We aimed at genotyping all possible known DNA rearrangements of intron 22 of F8
      in Egyptian HA patients. Peripheral blood samples were collected from 30 Egyptian
      HA patients (13 severe, ten moderate, and seven mild cases). Genotyping of F8
      intron 22 rearrangements was performed by inverse-shifting PCR (IS-PCR). Our
      study revealed that seven patients (23.3%) had inversion 22, three patients (10%)
      had deletion 22, and 20 patients (66.7%) carried the wild-type allele. No intron
      22 duplication was detected. The relative proportion of inversion 22-type 1 to
      inversion 22-type 2 was 85.7% and 14.3%, respectively, whereas the relative
      proportion of deletion 22-type 1 to deletion 22-type 2 was 33.3% and 66.7%,
      respectively. A statistically highly significant relation was found between
      disease severity and F8 intron 22 rearrangements (p = 0.008). Among severe cases,
      46.1% had inversion 22, 23.1% had deletion 22, and 30.8% carried the wild-type
      allele. We conclude that F8 intron 22 inversion/deletion is responsible for about
      one third of disease-causing mutations among Egyptian hemophiliacs and for nearly
      70% in severe cases. In addition, F8 intron 22 inversion/deletion by IS-PCR has
      proven to be a rapid and robust technique and might be the recommended tool for
      genetic analysis of HA patients specially with severe cases in developing
      countries.

PMID- 21072518
TI  - Gemcitabine and vinorelbine combination is effective in both as a salvage and
      mobilization regimen in relapsed or refractory Hodgkin lymphoma prior to ASCT.
AB  - We investigated the efficacy of gemcitabine and vinorelbine (Gem/Vin) combination
      chemotherapy as a salvage and mobilization regimen in relapsed or refractory
      Hodgkin lymphoma (HL) patients prior to autologous hematopoietic stem cell
      transplantation. We retrospectively reviewed the data of our relapsed or primary
      refractory HL patients treated with Gem/Vin regimen which consisted of
      gemcitabine 1,000 mg/m(2)/day and vinorelbine 30 mg/m(2)/day on days 1, 8, and 15
      every 28 days. The overall response rate was 72.4%. Ten (34.5%) patients achieved
      complete remission, 11 (37.9%) partial remission, and eight (27.6%) patients had
      no response. Mobilization with Gem/Vin regimen was successful in 20/23 (87%)
      patients while mobilization failure was seen in three (13%) patients. Gemcitabine
      and vinorelbine is an effective salvage regimen with acceptable toxicity and high
      mobilization potential in relapsed or refractory HL patients.

PMID- 21072519
TI  - Cytotoxic responses to N-(4-hydroxyphenyl)retinamide in human pancreatic cancer
      cells.
AB  - PURPOSE: Although fenretinide (4-HPR) has been studied in breast cancer and in
      neuroblastoma, little is known regarding its activity in pancreatic cancer, a
      neoplasm for which there are few therapeutic options. Since pancreatic cancer
      cells are susceptible to reactive oxygen species (ROS) and ceramide, two
      hallmarks of 4-HPR cytotoxicity, we investigated the effect of 4-HPR on human
      pancreatic cancer cells. METHODS: Human pancreatic cancer cell lines MIA PaCa-2
      and PANC-1 were treated with 4-HPR, followed by measurement of viability,
      proliferation, ROS and ceramide production, and Western blotting. RESULTS: At the
      measured IC(50) of 10 MUM, 4-HPR led to a 44-68% reduction in [(3)H]thymidine
      incorporation, a >3-fold increase in de novo ceramide levels, a 2.7-fold increase
      in ROS, and minor increases in markers of apoptosis. 4-HPR induced a robust,
      sustained increase in LC3 II expression and enhanced formation of acridine orange
      stained acidic vesicles that are markers of autophagy. In addition, sustained,
      dose-dependent increases in JNK and p38 phosphorylation and decreased ERK
      phosphorylation were observed following treatment. Pretreatment with vitamin E, a
      ROS scavenger, and 3-methyladenine, an autophagy inhibitor, individually led to
      decreased sensitivity to 4-HPR; however, the de novo ceramide inhibitor myriocin
      had no effect. CONCLUSIONS: These data show that 4-HPR triggers pancreatic cancer
      cell death by apoptosis and autophagy and that sensitivity appears to be mediated
      by ROS and not ceramide. This study is the first to characterize the response of
      human pancreatic cancer cells to 4-HPR and opens the door to investigations into
      this compound in pancreatic adenocarcinomas.

PMID- 21072520
TI  - Antitumor effects of (S)-HDAC42, a phenylbutyrate-derived histone deacetylase
      inhibitor, in multiple myeloma cells.
AB  - PURPOSE: Epigenetic agents are among the newly targeted therapeutic strategies
      being studied with intense interest for patients with multiple myeloma. Here, we
      demonstrate the antitumor activity of a phenylbutyrate-based histone deacetylase
      (HDAC) inhibitor, (S)-HDAC42, and identify its possible targets in myeloma cells.
      METHODS: The antiproliferative effect of (S)-HDAC42 was compared with
      suberoylanilide hydroxamic acid (SAHA) in three myeloma cell lines, IM-9, RPMI
      8226, and U266. Flow cytometry and terminal transferase dUTP nick-end labeling
      (TUNEL) assay were used to demonstrate the induction of apoptosis by (S)-HDAC42.
      Moreover, the proposed mechanisms of action, such as modulation of Akt, NF-kappaB
      pathway, and cell cycle-related proteins, were investigated by western blotting.
      RESULTS: (S)-HDAC42 exhibited four- to sevenfold higher potency relative to SAHA
      in suppressing myeloma cell viabilities. The apoptotic effect induced by (S)
      HDAC42 was through both intrinsic and extrinsic pathways, as evidenced by
      increased cleavage of caspase-3, caspase-8, and caspase-9 and release of
      cytochrome c from mitochondria. In addition to HDAC inhibition, (S)-HDAC42 also
      disturbed signaling pathways governing cell survival, including downregulating
      Akt phosphorylation and NF-kappaB signaling. The modulation of cell cycle-related
      proteins by (S)-HDAC42 suggested its inhibitory effect on cell cycle propagation.
      CONCLUSION: These data suggest the translational value of (S)-HDAC42 in
      developing new therapeutic strategies for myeloma, which warrants further
      investigations.

PMID- 21072522
TI  - Bats and frogs and animals in between: evidence for a common central timing
      mechanism to extract periodicity pitch.
AB  - Widely divergent vertebrates share a common central temporal mechanism for
      representing periodicities of acoustic waveform events. In the auditory nerve,
      periodicities corresponding to frequencies or rates from about 10 Hz to over
      1,000 Hz are extracted from pure tones, from low-frequency complex sounds (e.g.,
      1st harmonic in bullfrog calls), from mid-frequency sounds with low-frequency
      modulations (e.g., amplitude modulation rates in cat vocalizations), and from
      time intervals between high-frequency transients (e.g., pulse-echo delay in bat
      sonar). Time locking of neuronal responses to periodicities from about 50 ms down
      to 4 ms or less (about 20-300 Hz) is preserved in the auditory midbrain, where
      responses are dispersed across many neurons with different onset latencies from 4
      5 to 20-50 ms. Midbrain latency distributions are wide enough to encompass two or
      more repetitions of successive acoustic events, so that responses to multiple,
      successive periods are ongoing simultaneously in different midbrain neurons.
      These latencies have a previously unnoticed periodic temporal pattern that
      determines the specific times for the dispersed on-responses.

PMID- 21072521
TI  - Analysis of target sequences of DDM1s in Brassica rapa by MSAP.
AB  - DNA methylation is an important epigenetic modification regulating gene
      expression and transposon silencing. Although epigenetic regulation is involved
      in some agricultural traits, there has been relatively little research on
      epigenetic modifications of genes in Brassica rapa, which includes many important
      vegetables. In B. rapa, orthologs of DDM1, a chromatin remodeling factor required
      for maintenance of DNA methylation, have been characterized and DNA
      hypomethylated knock-down plants by RNAi (ddm1-RNAi plants) have been generated.
      In this study, we investigated differences of DNA methylation status at the
      genome-wide level between a wild-type (WT) plant and a ddm1-RNAi plant by
      methylation-sensitive amplification polymorphism (MSAP) analysis. MSAP analysis
      detected changes of DNA methylation of many repetitive sequences in the ddm1-RNAi
      plant. Search for body methylated regions in the WT plant revealed no difference
      in gene body methylation levels between the WT plant and the ddm1-RNAi plant.
      These results indicate that repetitive sequences are preferentially methylated by
      DDM1 genes in B. rapa.

PMID- 21072523
TI  - Craniopharyngiomas in children: how radical should the surgeon be?
AB  - PURPOSE: Two main modes of management of craniopharyngiomas, namely, radical
      tumor removal and intentional incomplete removal followed by radiotherapy, are
      used. Recently, a half-way solution was added. Radical removal is reserved only
      for the tumors not involving hypothalamus. Such tumors, however, are not clearly
      defined. The goal of the study was to clarify the relationship of
      craniopharyngiomas with surrounding structures, especially hypothalamus, and to
      evaluate its clinical significance. METHODS: Our policy of management of
      craniopharyngiomas was elaborated on the basis of the results of morphological
      studies of the topography and their correlation with magnetic resonance imaging
      (MRI) in 115 adults and children operated on since 1991. Suitability of the
      policy in children and adolescents was verified by long-term outcome analysis in
      41 consecutive patients. RESULTS: The rate of morbidity and mortality was higher
      in patients with craniopharyngiomas located inside the third ventricle either
      partially (intraventricular and extraventricular craniopharyngiomas, IEVCs, 16
      patients) or completely (intraventricular, one patient) than in tumors located
      outside the ventricle (suprasellar extraventricular, SEVCs, five patients;
      intrasellar and suprasellar, 19 patients). Postsurgical hypothalamic signs and
      symptoms occurred most often in intraventricular tumors; there were no mental
      disorders or obesity caused by primary removal of SEVCs including those severely
      compressing hypothalamus. CONCLUSIONS: Radical removal of SEVCs is safer than of
      IEVCs despite an apparent involvement of hypothalamus. In majority of cases, they
      may be distinguished by indirect MRI signs; in others only according to operation
      findings; final decision about the optimal extent of tumor removal should be made
      during surgery.

PMID- 21072524
TI  - Discrepant electrophysiological characteristics and calcium homeostasis of left
      atrial anterior and posterior myocytes.
AB  - The left atrial (LA) posterior wall has been demonstrated to have regional
      electrophysiological differences with a higher arrhythmogenic potential leading
      to atrial fibrillation (AF). However, the ionic characteristics and calcium
      regulation in the LA anterior and posterior myocytes have not been fully
      elucidated. The purpose of this study was to investigate the electrical
      characteristics of the LA anterior and posterior myocytes. Whole-cell patch-clamp
      techniques and the indo-1 fluorimetric ratio technique were used to investigate
      the characteristics of the ionic currents, action potentials, and intracellular
      calcium in single isolated rabbit myocytes in the LA anterior and posterior
      walls. The expression of the Na(+)-Ca(2+) exchanger (NCX) and ryanodine receptor
      (RyR) were evaluated by a Western blot. The LA posterior myocytes (n = 15) had a
      higher incidence (53 vs. 19%, P < 0.05) of delayed afterdepolarizations than the
      LA anterior myocytes (n = 16). The LA posterior myocytes had larger sodium
      currents and late sodium currents, but smaller inward rectifier potassium
      currents than the LA anterior myocytes. The LA posterior myocytes had larger
      intracellular Ca(2+) transient and sarcoplasmic reticulum Ca(2+) contents as
      compared with the LA anterior myocytes. However, the NCX currents in the LA
      posterior myocytes were smaller than those in the LA anterior myocytes. The LA
      posterior myocytes had a smaller protein expression of NCX, but a larger protein
      expression of RyR than the LA anterior myocytes. In conclusion, LA posterior
      myocytes contain a high arrhythmogenic potential and distinctive
      electrophysiological characteristics, which may contribute to the pathophysiology
      of AF.

PMID- 21072525
TI  - The association between inherited thrombophilias and pregnancy-related
      hypertension recurrence.
AB  - PURPOSE: The aim of this study was to determine the association between inherited
      thrombophilias and pregnancy-related hypertension recurrence. METHODS: In this
      case-control study, blood samples were obtained from patients who had at least
      two pregnancies complicated with pregnancy-related hypertension (n = 41) and
      healthy, normotensive pregnancies delivered without any complication (n = 38).
      Following the DNA extraction, samples were tested for factor V Leiden,
      prothrombin G20210A and homozygous methylene tetrahydrofolate reductase (MTHFR)
      C677T mutations using reverse hybridization method. RESULTS: Common inherited
      thrombophilias were present in 26.8% of women with recurrent pregnancy-related
      hypertension group and 23.7% of control subjects (odds ratio 1.1; 95% confidence
      interval, 0.6-1.9). No significant difference was observed between two groups in
      terms of factor V Leiden, prothrombin G20210A and MTHFR C677T mutations.
      CONCLUSION: Our data suggest that factor V Leiden, prothrombin G20210A and MTHFR
      C677T mutations are not associated with pregnancy-related hypertension
      recurrence.

PMID- 21072526
TI  - Pregnancy, obesity, gestational weight gain, and parity as predictors of
      peripartum complications.
AB  - PURPOSE: To determine if the best predictor of pregnancy complications is pre
      pregnancy body mass index (BMI) alone or in combination with other factors.
      METHODS: BMI and peripartum outcomes of singleton pregnancies were evaluated.
      Recursive partitioning and logistic regression modeling was used. RESULTS: Of the
      4,286 cohorts, 26% were obese (BMI >30 kg/m(2)) and, compared to cohorts with
      normal weight, at risk for wound infections (P < 0.001), and shoulder dystocia (P
      < 0.001). High-risk patients (15%; BMI >32.5, parity, pregnancy weight gain of 28
      lb by 28 weeks) were at increased risk for wound infection (P < 0.001),
      endometritis (P < 0.001), shoulder dystocia (P = 0.001) and 5 min Apgar score <4
      (P < 0.041) and at lower risk for pre-term delivery (P = 0.007). CONCLUSIONS:
      Since BMI, parity, and weight gain until 28 weeks together provide better
      prediction of peripartum complications than BMI alone, these characteristics can
      be used to triage and refer patients.

PMID- 21072527
TI  - Nifedipine for the treatment of preterm labor in twin and singleton pregnancies.
AB  - PURPOSE: To investigate the outcomes of singleton and twin pregnancies that were
      complicated by spontaneous preterm labor and received nifedipine tocolysis.
      METHODS: We identified the following subjects from a computerized, hospital
      database: 58 singleton and 32 twin pregnancies that were between 24 and 34 weeks
      of gestation, admitted for spontaneous preterm labor without rupture of the
      membranes, and receiving tocolysis with nifedipine. Data were analyzed using the
      Chi-square test, the Mann-Whitney test, and the Kaplan-Meier survival analysis.
      RESULTS: Spontaneous, preterm delivery occurred in 31.1% cases of singleton and
      81.3% of twin pregnancies. Although the 22% of the mothers of twins did not have
      cervical changes upon admission, 37% of twins were delivered within 48 h. Mean
      for delivery weeks from admission to 36 weeks was significantly less for twin
      than it was for singleton gestations (32.3 +/- 1.0 vs. 35.0 +/- 0.5 weeks,
      respectively; Mantel-Cox X (2) = 41.118; p < 0.001). The maternal side effects
      were not significantly different between the groups. No serious cardiovascular
      complication had been found in either group. CONCLUSIONS: Tocolysis with
      nifedipine is effective and safe for use in both singleton and twin gestations.

PMID- 21072528
TI  - Laryngeal effects of nasal allergen provocation in singers with allergic
      rhinitis.
AB  - In spite of our recent insight into nasobronchial interaction mechanisms in
      allergic airway disease, the association between allergic rhinitis and voice
      complaints remains obscure. To evaluate the effects of nasal allergen provocation
      and seasonal grass pollen exposure on subjective and objective laryngeal
      parameters in singers with and without allergic rhinitis, an observational case
      control study was conducted. Prior to the pollen season, six grass pollen
      allergic and six non-allergic semiprofessional singers were exposed to nebulized
      sham solution and grass pollen extract (HAL degrees ) in rising concentrations.
      After 3 min, 60 min and 24 h, nasal and laryngeal complaints were evaluated by
      the use of a visual analog scale (VAS). Laryngeal parameters like voice
      appearance (video stroboscopic images), voice range profile and subjective
      (GRBAS) and objective (jitter, shimmer, H/N, DSI) voice quality were evaluated
      before provocation, after 60 min and 24 h. During the pollen season, the allergic
      singers were re-evaluated. Results showed that in allergic singers both nasal
      (TNS of 4.0 +/- 2.4 vs. 0.0 +/- 0.0, p < 0.05) and laryngeal complaints (TLS of
      1.4 +/- 1.1 vs. 0.0 +/- 0.2, p < 0.05) were induced at 3 min after the
      provocation. The induced laryngeal complaints were the feeling of laryngeal
      irritation, secretions and globus. No change in voice quality or stroboscopy
      score was measured. During the pollen season, laryngeal complaints were present
      (TLS of 2.4 +/- 2.4) in allergic singers, without evidence for objective voice
      and laryngeal changes. In conclusion, we here demonstrate the rapid induction of
      laryngeal complaints in allergic singers by nasal allergen provocation and during
      the pollen season. There was no subject reported or investigator measured change
      in voice quality. No change in stroboscopy score was measured.

PMID- 21072529
TI  - Increasing incidence of differentiated thyroid cancer in South East England: 1987
      2006.
AB  - There has been a worldwide increase in the incidence of thyroid cancer (TC).
      Documenting these recent trends is of immense value to cancer control measures,
      monitoring policies, improving clinical outcomes, resource allocation and
      stimulating research. Hence this study aimed to analyse the changes in incidence,
      staging and morphologic types of TC in South East England (1987-2006) by means of
      a retrospective, descriptive epidemiological study using anonymized data obtained
      from the Thames Cancer Registry (TCR) of all patients registered with TC in the
      period 1987-2006. Ethical approval was obtained from the Kent Research Ethics
      Committee. 4,880 anonymized datasets using the ICD-10 code for thyroid cancer
      (C73) were analyzed using SPSS v.17. TC was commoner amongst females 3,560 (73%)
      than males 1,320 (27%) with a 2.7:1 ratio. Mean age at diagnosis was 53 years
      (Range 5-99) years. An increasing incidence trend was observed in early stage
      disease (p < 0.001), in young adults aged <= 49 years (p < 0.001) and in well
      differentiated TC (papillary p < 0.001 and follicular p = 0.03). The results
      showed that TC is commoner in females than males in SE England with a 2.7:1
      ratio. The results also indicate that TC incidence has increased in SE England
      over the 20 years studied, with the greatest increase occurring in early stage
      disease, in females, young adults and well-differentiated types (papillary and
      follicular). This may be due to widespread usage of ultrasound with detection of
      incidental nodules. Further studies are required to explain the trend.

PMID- 21072530
TI  - Progressive external ophthalmoplegia as initial manifestation of sporadic late
      onset nemaline myopathy.

PMID- 21072531
TI  - Management of punding in Parkinson's disease: an open-label prospective study.
AB  - Punding, a peculiar stereotyped behavior characterized by intense fascination
      with complex, excessive, non-goal-oriented, repetitive activities, is a quite
      rare condition complicating Parkinson's disease (PD). It is triggered by
      dopaminergic therapy and could have a strong impact on patient quality of life.
      No study has specifically investigated medical management of this condition, and
      only a few anecdotal reports have provided therapeutic hints. Given the suggested
      similarities to drug-induced dyskinesias, we have previously suggested a
      multistep algorithm for management of punding. We conducted a prospective open
      label study on ten PD punders aimed at testing its validity. In two cases,
      reduction of levodopa therapy was efficacious; amantadine was effective in
      controlling punding in four cases; in the remaining cases, quetiapine was
      employed, with mild efficacy in two cases.

PMID- 21072532
TI  - Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared
      haplotype on chromosome 9p.
AB  - Families with autosomal dominant frontotemporal dementia and amyotrophic lateral
      sclerosis (FTD/ALS) have previously been linked to a locus on chromosome 9p21. We
      describe the clinical phenotype and pathology of a large family with autosomal
      dominant FTD/ALS with nine affected members originating from Gwent in South
      Wales, UK. We also further refine the locus on chromosome 9p21 using a haplotype
      sharing approach and assess heterogeneity in 9p21 linked families. Within this
      family, affected individuals present with either FTD or ALS or both diseases
      simultaneously. In addition there was marked phenotypic variation including
      ataxia, Parkinsonism, psychosis and visuo-spatial cognitive deficits. The
      pathological features of the three cases described were consistent with type 2
      FTD pathology, as previously reported in similar families. However, we also
      report distinctive cerebellar and glial pathology and a significant proportion of
      TDP-43 negative inclusions. No mutations in known genes for FTD or ALS were
      found. We identified a large 4.8-megabase haplotype on chromosome 9p21, which was
      shared by all affected family members. This haplotype overlaps and limits the
      previously reported FTD/ALS linkage region on chromosome 9p21. Sequencing of this
      region did not identify any evidence of a pathogenic exonic mutation. This
      suggests that the pathogenic change affects non-coding DNA and that the disease
      is caused by variation in gene or protein expression.

PMID- 21072533
TI  - Urinary symptoms and urodynamic findings in patients with Machado-Joseph disease.
AB  - The study evaluated the prevalence of clinical and urodynamic findings in the
      lower urinary tract of patients with Machado-Joseph (MJ) disease. One hundred
      twenty-two patients were retrospectively evaluated; 17 (13.9%) presented lower
      urinary tract dysfunction, 10 of them were women. The average age was 41.6 years.
      Urgency was found in 15 patients and incontinence in nine. The urodynamic study
      showed detrusor overactivity in eight patients, areflexia in one, and four with
      normal detrusor contractility. Bladder sensitivity was abnormal in six, bladder
      capacity was decreased in one, urine flow decreased in 13, post-voiding residue
      was greater than 100 ml in nine. We could not find sphincter dyssynergia. The
      average cytosine-adenine-guanine (CAG) repetition was higher in patients with
      abnormal detrusor contraction (89.9) than in patients with normal urodynamics
      (68.2) (p = 0.03). There was no statistical significance when comparing the
      averages of replicates for people with and without urgency urinary incontinence
      (p = 0.27 and p = 0.5, respectively). The rate of lower urinary tract dysfunction
      in patients with MJ disease was around 14%. The urodynamic study showed
      predominance of detrusor overactivity and urgency as the most common symptom. We
      found an association between the total number of CAG repetitions and changes in
      detrusor contractility.

PMID- 21072534
TI  - 'Switching off' SUNCT by sudden head movement: a new symptom.

PMID- 21072535
TI  - Intestinal ischemia: current treatment concepts.
AB  - PURPOSE: Mesenteric ischemia is a condition well-known among physicians treating
      patients with abdominal symptoms. Even so, mortality rates have not decreased
      significantly over the last decades. The purpose of this article is to review
      current treatment concepts of acute and chronic mesenteric ischemia. RESULTS:
      Early diagnosis is one of the most important features that determine a patient's
      prognosis. Conventional angiography and multidetector computed tomography are
      therefore appropriate to quickly diagnose mesenteric ischemia, the latter being
      commonly more available. Once a patient presents with signs of peritonitis,
      instant laparotomy is indicated, and infarcted bowel segments need to be
      resected, followed by a second-look operation if necessary. If bowel necrosis is
      clinically not suspected, different approaches should be applied according to
      source and nature of mesenteric ischemia. Besides established surgical treatment
      concepts, more and more interventional procedures are developed and evaluated.
      However, superiority of these new techniques could only be shown for selected
      patient groups so far. In chronic mesenteric ischemia, interventional approaches
      seem to be an attractive alternative in patients who are in a condition too bad
      to undergo surgery. Patients with colonic ischemia are treated best in a
      conservative manner and by resolving the underlying cause, if identified.
      CONCLUSION: Patients with acute mesenteric ischemia are still at highest risk for
      a fatal course of disease. New diagnostic and therapeutic developments have not
      been tested in larger studies yet, neither has any of these methods led to an
      increased survival in studies published so far. Taken together, mesenteric
      ischemia requires high awareness, earliest possible diagnosis, and treatment by
      an experienced interdisciplinary team of gastroenterologists, radiologists, and
      surgeons.

PMID- 21072536
TI  - Monitoring prevalence of varicella-zoster virus clades in Germany.
AB  - The global surveillance of varicella-zoster virus (VZV) clades is an important
      tool for investigation into viral evolution, host-virus interactions, role of
      immigration and travel for importation of viral strains as well as possible
      recombination events between wild- and vaccine-type VZV strains. In this
      prospective study, comprehensive data on the current distribution of VZV clades
      in Germany were collected. VZV strains from 213 patients with varicella and 109
      with zoster were genotyped using the scattered single-nucleotide polymorphism
      method on the basis of sequencing open reading frames 1, 21, 22, 37, 50, 54 and
      60. In varicella, clade 3 was detected in 45.5%, clade 1 in 30.0%, clade 5 in
      21.1% and clade 2 in 0.9% of the cases. The analysis of zoster strains revealed
      clade 3 in 50.5%, clade 1 in 46.8%, clade 2 and clade 4 in 0.9% of the cases
      each. Five strains from varicella and one strain from zoster could not be
      attributed to any of the major and provisional VZV clades. Statistical analysis
      verified significantly lower frequency of clade 1 and significantly higher
      frequency of clade 5 in patients with varicella compared to zoster. In addition,
      varicella patients with clade 5 strains were significantly younger than the
      patients with clade 3. In conclusion, almost one half of VZV infections in
      Germany were caused currently by VZV clade 3. In primary VZV infection, nearly
      20% of clade 1 has been replaced by clade 5 that might spread more effectively in
      the population than the European VZV clades.

PMID- 21072537
TI  - Prenatal presentation of transient central diabetes insipidus.
AB  - INTRODUCTION: Nephrogenic diabetes insipidus (DI) in the foetus has been
      described as a rare presentation of severe polyhydramnios. DISCUSSION: We report
      a case of foetal central DI, characterised by severe polyhydramnios. Significant
      polyuria was noted at birth. Serum AVP level was un-measurable (<0.5 pg/ml). A
      dramatic response to intravenous dDAVP (desmopressin) was noted confirming
      central DI. Further investigations did not reveal a recognised cause for central
      or nephrogenic DI. The infant thrived well on a small dose of oral desmopressin
      until the age of 12 months. At 13 months, a water deprivation test revealed a
      normal ability to concentrate urine without desmopressin, and subsequently, the
      infant has thrived without further treatment. The transient nature of the central
      DI remains obscure but could be explained by a maturational delay in the tissues
      involved in AVP synthesis or release, during intrauterine life and infancy.
      CONCLUSION: Both nephrogenic and central DI should be considered as a cause of
      severe polyhydramnios. This may help to guide prompt intensive management and
      investigation, with attention to vascular access, central venous pressure, urine
      output monitoring and replacement.

PMID- 21072538
TI  - Identification of astigmatid mites using ITS2 and COI regions.
AB  - Identification of astigmatid mites based on their morphological characteristics
      is difficult because of the similarity of their organs, especially in immature
      mites. The ribosomal second internal transcribed spacer (ITS2) and the
      mitochondrial cytochrome oxidase subunit I (COI) regions are highly conserved in
      the eukaryotes and are usually used as barcodes. The ITS2 and COI regions of six
      species of astigmatid mites (Aleuroglyphus ovatus, Blomia tropicalis,
      Dermatophagoides farinae, Dermatophagoides pteronyssinus, Euroglyphus maynei,
      Tyrophagus putrescentiae) were obtained by polymerase chain reaction and
      sequenced. The lengths of the ITS2 sequences varied from 316 to 488 bp, while the
      COI regions were 377 or 378 bp long. Considering the ITS2 genes, the
      intraspecific genetic distance was in the range of 0.00-0.077844, whereas the
      interspecific genetic distance was 0.202426-0.912959. The values were 0.000
      0.029748 and 0.138403-0.279304 for intra- and interspecific genetic distances
      when COI genes were used. The phylogenetic trees inferred from the ITS2 and the
      COI regions, by using maximum parsimony and neighbor-joining methods, were
      identical to those based on their morphological classification. Thus, the ITS2
      and COI regions can be applied as barcodes to identify different species of
      astigmatid mites.

PMID- 21072539
TI  - PCR detection of Dirofilaria immitis in Aedes aegypti and Culex pipiens from
      urban temperate Argentina.
AB  - Dirofilariasis, a mosquito-borne disease of dogs caused by the nematode
      Dirofilaria immitis (Leidy; Spirurida: Onchocercidae), has now become a growing
      zoonotic concern. Based on direct microscopical observation, Aedes aegypti (L.)
      and Culex pipiens L. (Diptera: Culicidae) have been previously incriminated as
      potential vectors of D. immitis in urban temperate Argentina. In this study, an
      effort was made to provide evidence for this assumption by screening of
      mosquitoes for D. immitis infection using a polymerase chain reaction (PCR)
      assay. PCR primers were developed to specifically amplify the D. immitis-16S rRNA
      gene and to reliably detect 100th of the genomic equivalent (10 pg) of the
      infective third-stage larvae in mosquito pools of up to 30 individuals.
      Collection of mosquitoes was performed between September 2007 and April 2008 in
      premises known to be inhabited by D. immitis-infected dogs in Greater Buenos
      Aires. The final collection comprised 453 specimens belonging to 11 mosquito
      species of the genera Aedes, Culex, Ochlerotatus, and Psorophora. PCR assays were
      performed on 82 pools (n <= 20) of heads and abdomens separately, as this allows
      differentiating infective and non-infective stages of the parasite, respectively.
      Identification of the non-infective stage of D. immitis in A. aegypti and C.
      pipiens provided additional strong support of transmission of the parasite by
      these species. To our knowledge, this was the first PCR screening for D. immitis
      infected mosquitoes in South America.

PMID- 21072541
TI  - Landscape-scale feeding patterns of African elephant inferred from carbon isotope
      analysis of feces.
AB  - The African elephant (Loxodonta africana) is a large-bodied, generalist herbivore
      that eats both browse and grass. The proportions of browse and grass consumed are
      largely expected to reflect the relative availability of these resources. We
      investigated variations in browse (C(3) biomass) and grass (C(4)) intake of the
      African elephant across seasons and habitats by stable carbon isotope analysis of
      elephant feces collected from Kruger National Park, South Africa. The results
      reflect a shift in diet from higher C(4) grass intake during wet season months to
      more C(3) browse-dominated diets in the dry season. Seasonal trends were
      correlated with changes in rainfall and with nitrogen (%N) content of available
      grasses, supporting predictions that grass is favored when its availability and
      nutritional value increase. However, switches to dry season browsing were
      significantly smaller in woodland and grassland habitats where tree communities
      are dominated by mopane (Colophospermum mopane), suggesting that grasses were
      favored here even in the dry season. Regional differences in diet did not reflect
      differences in grass biomass, tree density, or canopy cover. There was a
      consistent relationship between %C(4) intake and tree species diversity, implying
      that extensive browsing is avoided in habitats characterized by low tree species
      diversity and strong dominance patterns, i.e., mopane-dominated habitats.
      Although mopane is known to be a preferred species, maintaining dietary diversity
      appears to be a constraint to elephants, which they can overcome by supplementing
      their diets with less abundant resources (dry season grass). Such variations in
      feeding behavior likely influence the degree of impact on plant communities and
      can therefore provide key information for managing elephants over large,
      spatially diverse, areas.

PMID- 21072540
TI  - Characterization of Leishmania spp. causing cutaneous leishmaniasis in Manaus,
      Amazonas, Brazil.
AB  - In the State of Amazonas, American tegumentary leishmaniasis is endemic and
      presents a wide spectrum of clinical variability due to the large diversity of
      circulating species in the region. Isolates from patients in Manaus and its
      metropolitan region were characterized using monoclonal antibodies and isoenzymes
      belonging to four species of the parasite: Leishmania (Viannia) guyanensis, 73%
      (153/209); Leishmania (Viannia) braziliensis, 14% (30/209); Leishmania
      (Leishmania) amazonensis, 8% (17/209); and Leishmania (Viannia) naiffii, 4%
      (9/209). The most prevalent species was L. (V.) guyanensis. The principal finding
      of this study was the important quantity of infections involving more than one
      parasite species, representing 14% (29/209) of the total. The findings obtained
      in this work regarding the parasite are further highlighted by the fact that
      these isolates were obtained from clinical samples collected from single lesions.

PMID- 21072542
TI  - Simple ecological trade-offs give rise to emergent cross-ecosystem distributions
      of a coral reef fish.
AB  - Ecosystems are intricately linked by the flow of organisms across their
      boundaries, and such connectivity can be essential to the structure and function
      of the linked ecosystems. For example, many coral reef fish populations are
      maintained by the movement of individuals from spatially segregated juvenile
      habitats (i.e., nurseries, such as mangroves and seagrass beds) to areas
      preferred by adults. It is presumed that nursery habitats provide for faster
      growth (higher food availability) and/or low predation risk for juveniles, but
      empirical data supporting this hypothesis is surprisingly lacking for coral reef
      fishes. Here, we investigate potential mechanisms (growth, predation risk, and
      reproductive investment) that give rise to the distribution patterns of a common
      Caribbean reef fish species, Haemulon flavolineatum (French grunt). Adults were
      primarily found on coral reefs, whereas juvenile fish only occurred in non-reef
      habitats. Contrary to our initial expectations, analysis of length-at-age
      revealed that growth rates were highest on coral reefs and not within nursery
      habitats. Survival rates in tethering trials were 0% for small juvenile fish
      transplanted to coral reefs and 24-47% in the nurseries. As fish grew, survival
      rates on coral reefs approached those in non-reef habitats (56 vs. 77-100%,
      respectively). As such, predation seems to be the primary factor driving across
      ecosystem distributions of this fish, and thus the primary reason why mangrove
      and seagrass habitats function as nursery habitat. Identifying the mechanisms
      that lead to such distributions is critical to develop appropriate conservation
      initiatives, identify essential fish habitat, and predict impacts associated with
      environmental change.

PMID- 21072543
TI  - Influence of drying methods over in vitro antitumoral effects of
      exopolysaccharides produced by Agaricus blazei LPB 03 on submerged fermentation.
AB  - Agaricus blazei is a mushroom that belongs to the Brazilian biodiversity and is
      considered as an important producer of bioactive compounds beneficial to human
      health. Studies have demonstrated that these compounds present immuno-modulatory,
      antioxidant and antitumor properties. In order to compare the most used method
      for fungal polysaccharide drying, lyophilization with other industrial-scale
      methods, the aim of this work was to submit A. blazei LPB 03 polysaccharide
      extracts to vaucum, spray and freeze drying, and evaluate the maintenance of its
      antitumoral effects in vitro. Exopolysaccharides produced by A. blazei LPB 03 on
      submerged fermentation were extracted with ethanol and submitted to drying
      processes. The efficiency represents the water content that was removed during
      the drying process. The resultant dried products showed water content around 3%
      and water activity less than 0.380, preventing therefore the growth of
      microorganisms and reactions of chemical degradation. Exopolysaccharide extracts
      dried by vacuum and spray dryer did not showed any significant cytotoxic effect
      on cell viability of Wistar mice macrophages. Content of total sugars and protein
      decrease after drying, nevertheless, 20 mg/ml of exopolysaccharides dried by
      spray dryer reached 33% of inhibition rate over Ehrlich tumor cells in vitro.

PMID- 21072544
TI  - A 50-year experience with autoimmune hepatitis: and where are we now?
AB  - BACKGROUND: Autoimmune hepatitis (AIH) as chronic active hepatitis became
      recognized in the 1940s as a progressive hyperglobulinemic disease affecting
      younger women attributed to persisting virus infection of the liver: autoimmunity
      then was barely on the horizon. EARLY OBSERVATIONS: The lupus erythematosus (LE)
      cell reported in 1948 signified the presence of antinuclear autoantibodies,
      promoting perceptions of autoimmunity in certain chronic diseases. Recognition of
      LE cells in chronic hepatitis led to the designation of 'lupoid hepatitis', with
      autoimmunity further substantiated by anti-cytoplasmic autoantibodies detected by
      complement fixation. Next a serum reactant with smooth muscle of rodent stomach
      was found to have a wider distribution and became identified as an autoantibody
      to filamentous (F) actin. Therapy with corticosteroids proved effective,
      particularly combined with azathioprine. Various trials showed greatly improved
      survival and established modern therapy of AIH. An HLA-based predisposition (B8,
      DR3) was the first pointer to a genetic etiology. RECENT ADVANCES: Recombinant or
      purified autoantigenic substrates have led to automated assays, which, together
      with improved immunofluorescence procedures, allow serological confidence in
      diagnosis and institution of effective immunosuppressive therapies. The liver
      kidney 'microsomal' autoantigen reactive with cytochrome P450 2D6 distinguishes
      two serological types of AIH that appear pathogenetically distinct. Molecular
      characterization of antigens and epitopes remains wanting in type 1 AIH. FUTURE
      PROSPECTS: The challenge remains with both types of AIH to elucidate in molecular
      terms the genetic and environmental basis of pathogenesis from initiation to
      ultimate progression and cirrhosis (when inadequately treated). Advancing
      technologies are bringing this goal closer to being attainable.

PMID- 21072545
TI  - Back muscle strength and spinal mobility are predictors of quality of life in
      middle-aged and elderly males.
AB  - With aging of society, clarification of the relationship between QOL and abnormal
      posture in the elderly may allow improvement of QOL through any preventive
      methods and training. However, sagittal balance has not been studied widely and
      most studies have focused on postmenopausal patients with osteoporosis. In this
      report, we provide the first evaluation of the simultaneous effects of
      degenerative changes on radiograph, spinal range of motion (ROM), sagittal
      balance, and back muscle strength, and examine the influence of these effects on
      QOL of the middle-aged and elderly male subjects. The subjects were 100 Japanese
      males who underwent a basic health checkup. Lumbar lateral radiograph, sagittal
      balance and spinal mobility determined with SpinalMouse((r)) and back muscle
      strength were measured. The thoracic/lumbar angle ratio (T/L ratio) was used as
      an index of sagittal balance. SF-36 physical component summary (PCS) scores
      showed a significant negative correlation with age (r = -0.377), osteophyte score
      (r = -0.246) and T/L ratio (r = -0.214), and a significant positive correlation
      with lumbar lordosis angle (r = 0.271), thoracic ROM (r = 0.282), and back muscle
      strength (r = 0.549). Multiple regression analysis indicated that thoracic spinal
      ROM (r = 0.254, p < 0.01) and back muscle strength (r = 0.488, p < 0.0001) were
      significantly associated with SF-36 PCS (R (2) = 0.403). In conclusion, QOL of
      the middle-aged and elderly male subjects was related to sagittal balance, lumbar
      lordosis angle, spinal ROM, and back muscle strength. Exercise including muscle
      strength and spinal ROM may be able to influence these primary factors related to
      QOL. Back muscle strength and thoracic ROM impact on improvement of QOL in the
      middle-aged and the elderly.

PMID- 21072546
TI  - Impaired diastolic function and elevated Nt-proBNP levels in type 1 diabetic
      patients without overt cardiovascular disease.
AB  - Diabetic cardiomyopathy is an important complication of type 1 diabetes mellitus.
      Diastolic heart failure is an early manifestation of diabetic cardiac disease. Nt
      proBNP is a valuable marker of ventricular dysfunction. The aim of this study was
      to determine Nt-proBNP concentrations in type 1 diabetic patients and determine
      their relationship with ventricular diastolic dysfunction (DD) and carotid artery
      intima media thickness (CIMT) measurements. Sixty-seven type 1 diabetic patients
      (30.2 +/- 8.0 years; W/M: 24/43) without known cardiovascular disease and 48
      healthy controls (30.5 +/- 6.4 years; W/M: 19/29) were recruited. Nt-proBNP
      levels were measured. Conventional and tissue Doppler echocardiography were used
      to evaluate left ventricular diastolic function and CIMT. Nt-proBNP in diabetic
      patients was significantly higher than in controls (38 +/- 34.8 vs. 15.1 +/- 12.7
      pg/ml) (P = 0.004). Ea level was higher (12.3 +/- 3 vs. 10.3 +/- 4 cm/s, P =
      0.003) and E/Ea ratio was lower in patients (6.6 +/- 2.5 vs. 9.7 +/- 5.9, P =
      0.001) compared with controls. Ratio of DD was higher in patients than controls
      (11.1 vs. 2.1%, P = 0.01). CIMT measurements in diabetic patients were higher
      than controls (0.54 +/- 0.11 vs. 0.48 +/- 0.05 mm, P = 0.02). Logistic regression
      revealed age and HbA1c to be independently associated with the presence of DD. Nt
      proBNP levels are elevated in type 1 diabetic patients without overt
      cardiovascular disease and the presence of DD is increased in diabetic patients
      in comparison with controls. Nt-proBNP levels do not seem to be related to the
      presence of DD and subclinical atherosclerosis in this group of patients.

PMID- 21072547
TI  - Imaging plasmodesmata.
AB  - At only 50 nm in diameter, plasmodesmata (PD) are below the limit of resolution
      of conventional light microscopy. Consequently, much of our current
      interpretation of the substructure of PD is derived from transmission electron
      microscopy. However, PD can be imaged with alternative techniques, including
      field emission scanning electron microscopy and 'super-resolution' imaging
      approaches such as 3D-structured illumination microscopy. This review considers
      the methods currently available for studying PD and focuses on the boundary
      between light- and electron-based imaging approaches.

PMID- 21072548
TI  - The influence of parity on quantitative ultrasound evaluation of the calcaneus
      and hand phalanges in Polish postmenopausal women.
AB  - The aim of the retrospective study was to assess the influence of parity on the
      skeletal status in 760 postmenopausal women. Women with factors affecting their
      bone status, or those treated for osteoporosis, were not included. Quantitative
      ultrasound measurements were performed at the heel (Achilles, n = 465) or at hand
      phalanges (DBM Sonic 1200, n = 295). Regarding hand phalanges, Z score values
      were significantly lower in women with three, four, and five or six deliveries in
      comparison to nonparous women and in women with four deliveries versus women with
      one or two deliveries. Calcaneus ultrasound variables did not differ in regard to
      the number of deliveries. Stepwise multiple regression analysis has shown that
      the main factors, affecting the bone status, were postmenopause duration and body
      weight. We concluded the increasing number of deliveries negatively influences
      ultrasound measurements at hand phalanges, which suggests their role as a
      qualitative feature factor of cortical non-weight-bearing bone.

PMID- 21072549
TI  - Chondroma in temporomandibular region--case report and therapeutic
      considerations.
AB  - PURPOSE: Chondromas are benign tumors composed of mature hyaline cartilage. These
      tumors are quite common in the bones of the hands and feet but extremely rare in
      jaw bones, and few such cases are reported in the literature. The aim of the
      present study was to carry out a literature review and present a clinical case of
      a patient with a chondroma in the right mandibular condyle treated with excision
      of the tumor. CONCLUSIONS: The importance of early diagnosis and treatment in
      order to impede or minimize any lasting effects is discussed.

PMID- 21072550
TI  - Patient satisfaction, chronic pain, and quality of life after elective incisional
      hernia repair: effects of recurrence and repair technique.
AB  - PURPOSE: To determine the effects of repair technique and hernia recurrence on
      patient-reported outcomes after incisional hernia repair. METHODS: This cohort
      study included patients from sixteen Veteran's Affairs Medical Centers across the
      United States who underwent elective incisional hernia repair between 1997 and
      2002. Technical details and outcomes (repair type and recurrence status) were
      determined by physician chart review. Patient satisfaction, chronic pain (McGill
      pain scale and visual analogue scale), and health-related quality of life (Short
      Form 36) were evaluated with a mailed survey at a median of five years after
      repair. Multivariable regression modeling was performed to evaluate the effect of
      repair type and recurrence status on patient-reported outcomes. RESULTS: Of 854
      patients alive at the time of survey mailing, 371 responded (43.4%). Patients
      with active recurrence were more likely to be dissatisfied with their results
      (odds ratio (OR) 6.2, P < 0.0001), to have chronic sensory hernia site pain (OR
      3.2, P = 0.01), to report disturbance from pain (OR 2.1, P = 0.04), and to have
      significantly worse quality of life on the Physical Function, General Health, and
      Physical Component Score domains. Repair technique with permanent mesh versus
      suture had no independent effect on patient satisfaction, chronic pain, or QOL.
      CONCLUSIONS: Recurrence has a substantial negative effect on patient-reported
      outcomes after incisional hernia repair, whereas the repair technique has no
      independent effect.

PMID- 21072551
TI  - Human acellular dermal matrix for ventral hernia repair reduces morbidity in
      transplant patients.
AB  - PURPOSE: Organ transplantation is widely accepted as the treatment of choice for
      native organ failure. Due to required immunosuppression, however, organ
      recipients are prone to wound infections, incisional hernias, and fascial
      dehiscence. These complications are especially dangerous in this patient
      population, as they can compromise the survival of the transplanted organ.
      Various methods have been employed to repair ventral and incisional hernias in
      these patients. These include primary repair, synthetic mesh, biologic mesh,
      tensor fascia lata grafts (TFL), component separation, flaps from the thighs, or
      a combination of these. The goal of this study was to review the experience at
      our institution with ventral hernia repair in transplant patients and to compare
      outcomes of the various repair techniques. METHODS: Patients with liver, renal,
      or pancreas transplants requiring immunosuppression who underwent a ventral or
      incisional hernia repair at the University of Maryland from 2000-2005 were
      reviewed retrospectively. Factors examined include type and location of hernia,
      type of repair, post operative infection, hernia recurrence, reoperation, mesh
      removal, and length of follow up. Complication rates were compared using odds
      ratio and chi-square. RESULTS: A total of 104 patients met the criteria with a
      mean length of follow up of 26 months. Of these, 34 patients had repair with
      human acellular dermal matrix (HADM), 26 had synthetic mesh, 25 had primary
      repair, and 9 had TFL. Rates of wound infection in these groups were 15, 65, 8,
      and 11% respectively (chi (2) = 28, P < 0.001). Rates of recurrence were 24, 77,
      36, and 11% respectively (chi (2) = 22, P < 0.001). The rate of mesh removal with
      HADM and synthetic mesh were 12 and 69%, respectively (chi (2) = 14, P < 0.001).
      When comparing HADM and synthetic mesh, the odds ratio for wound infection is 11
      (95% CI 3.2-38) and for mesh removal is 8.7 (95% CI 2.6-28). CONCLUSION: When
      repairing ventral or incisional hernias in immunosuppressed transplant patients,
      HADM provides significantly reduced morbidity from reduced rates of infection,
      recurrence, and need for operative removal of mesh.

PMID- 21072552
TI  - Health-related quality of life in Moroccan patients with ankylosing spondylitis.
AB  - The main objective of this study was to assess the aspects of health-related
      quality of life (QOL) in patients with ankylosing spondylitis (AS) and to explore
      the disease-related parameters influencing it. One hundred patients with AS
      according to New York Classification criteria were recruited in this cross
      sectional study. The Medical Outcomes Study Short Form 36 Health Survey (SF-36)
      was used to assess health-related QOL. Assessment criteria included the
      evaluation of disease activity (Bath Ankylosing Spondylitis Disease Activity
      index [BASDAI]), global well-being (Bath Ankylosing Spondylitis Global Index
      [BASGI]), enthesitis (Mander enthesis index [MEI]), functional status (Bath
      Ankylosing Spondylitis Functional Index [BASFI]); metrology (Bath Ankylosing
      Spondylitis Metrology Index [BASMI]) and radiographic damage (Bath Ankylosing
      Spondylitis Radiologic Index [BASRI]). In this study, males comprised 67% of the
      subjects; mean age was 38 +/- 13 years and mean disease duration was 9.5 +/- 6.8
      years. Among these patients, 52% had hip involvement. Our patients had a
      moderately active disease and severe functional disability. All domains of SF-36
      were deteriorated with low scores. The SF-36 subgroups most affected were role
      limitation (18.8 +/- 28.1), role emotional (19.4 +/- 35), general health (44.9 +/
      20.3) and vitality (38.0 +/- 18.2). Lower scores of SF-36 had good statistically
      significant correlations with altered functional status (BASFI), worse general
      well-being (BASGI), altered metrology (BASMI); and moderate correlations with
      high disease activity (BASDAI), important radiological damage (BASRI); restricted
      chest expansion and prolonged morning stiffness (p < 0.001). This study states
      that health-related QOL in Moroccan patients with AS is damaged in a significant
      way. Mental as well as physical aspects were affected. Functional disability,
      patient's well-being, metrology and disease activity are the main factors
      associated with deteriorating domains of QOL in AS. Recognizing complicated
      relationships between clinical measures and QOL in patients with AS can help us
      to develop further management strategies to improve their QOL.

PMID- 21072553
TI  - Systemic lupus erythematosus, human papillomavirus infection, cervical pre
      malignant and malignant lesions: a systematic review.
AB  - The purpose of this study was to review and evaluate systematically the
      scientific evidence on the relationship between systemic lupus erythematosus
      (SLE), human papillomavirus (HPV) infection, pre-cancerous cervical
      abnormalities, and cervical cancer. Establishing strict inclusion and exclusion
      criteria, we performed an extensive search for studies in MEDLINE and BIREME
      databases to assess the studies that evaluated the frequency of HPV infection,
      pre-cancerous cervical abnormalities, and cervical cancer in women with SLE.
      Secondary references were additionally obtained from the included articles.
      Thirty-three articles met the criteria previously established. Fifteen out of 18
      studies that performed cytological analysis showed a higher frequency of squamous
      intraepithelial lesions in SLE patients compared with normal women. Moreover,
      three studies found a higher frequency of high-grade squamous intraepithelial
      lesions. Additionally, it was observed that women with SLE had a higher frequency
      of HPV infection, confirmed by molecular biology techniques. Curiously, despite
      the above findings, no increased frequency of cervical cancer was observed in the
      majority of the studies which addressed this issue. Five studies observed a
      relationship between cervical abnormalities and previous use of immunosuppressive
      drugs. This review suggests that SLE patients seem not to be at increased risk
      for developing cervical cancer; however, they should be considered at higher risk
      for HPV infection and cervical dysplasia than the general population. Thus,
      gynecological visits at shorter intervals seem to be a reasonable approach for
      those patients.

PMID- 21072554
TI  - Free energy of colloidal particles at the surface of sessile drops.
AB  - The influence of finite system size on the free energy of a spherical particle
      floating at the surface of a sessile droplet is studied both analytically and
      numerically. In the special case that the contact angle at the substrate equals
      pi/2 , a capillary analogue of the method of images is applied in order to
      calculate small deformations of the droplet shape if an external force is applied
      to the particle. The type of boundary conditions for the droplet shape at the
      substrate determines the sign of the capillary monopole associated with the image
      particle. Therefore, the free energy of the particle, which is proportional to
      the interaction energy of the original particle with its image, can be of either
      sign, too. The analytic solutions, given by the Green's function of the capillary
      equation, are constructed such that the condition of the forces acting on the
      droplet being balanced and of the volume constraint are fulfilled. Besides the
      known phenomena of attraction of a particle to a free contact line and repulsion
      from a pinned one, we observe a local free-energy minimum for the particle being
      located at the drop apex or at an intermediate angle, respectively. This
      peculiarity can be traced back to a non-monotonic behavior of the Green's
      function, which reflects the interplay between the deformations of the droplet
      shape and the volume constraint.

PMID- 21072556
TI  - A novel nonionic surfactant- and solvent-stable alkaline serine protease from
      Serratia sp. SYBC H with duckweed as nitrogen source: production, purification,
      characteristics and application.
AB  - A novel nonionic surfactant- and hydrophilic solvent-stable alkaline serine
      protease was purified from the culture supernatant of Serratia sp. SYBC H with
      duckweed as nitrogen source. The molecular mass of the purified protease is about
      59 kDa as assayed via SDS-PAGE. The protease is highly active over the pH range
      between 5.0 and 11.0, with the maximum activity at pH 8.0. It is also fairly
      active over the temperature range between 30 and 80 degrees C, with the maximum
      activity at 40 degrees C. The protease activity was substantially stimulated by
      Mn(2+) and Na(+) (5 mM), up to 837.9 and 134.5% at 40 degrees C, respectively. In
      addition, Mn(2+) enhanced the thermostability of the protease significantly at 60
      degrees C. Over 90% of its initial activity remained even after incubating for 60
      min at 40 degrees C in 50% (v/v) hydrophilic organic solvents such as DMF, DMSO,
      acetone and MeOH. The protease retained 81.7, 83.6 and 76.2% of its initial
      activity in the presence of nonionic surfactants 20% (v/v) Tween 80, 25% (v/v)
      glycerol and Triton X-100, respectively. The protease is strongly inhibited by
      PMSF, suggesting that it is a serine protease. Washing experiments revealed that
      the protease has an excellent ability to remove blood stains.

PMID- 21072557
TI  - Efficient chemical and enzymatic saccharification of the lignocellulosic residue
      from Agave tequilana bagasse to produce ethanol by Pichia caribbica.
AB  - Bagasse of Agave tequilana (BAT) is the residual lignocellulosic waste that
      remains from tequila production. In this study we characterized the chemical
      composition of BAT, which was further saccharified and fermented to produce
      ethanol. BAT was constituted by cellulose (42%), hemicellulose (20%), lignin
      (15%), and other (23%). Saccharification of BAT was carried out at 147  degrees C
      with 2% sulfuric acid for 15 min, yielding 25.8 g/l of fermentable sugars,
      corresponding to 36.1% of saccharificable material (cellulose and hemicellulose
      contents, w/w). The remaining lignocellulosic material was further hydrolyzed by
      commercial enzymes, ~8.2% of BAT load was incubated for 72 h at 40  degrees C
      rendering 41 g/l of fermentable sugars corresponding to 73.6% of the
      saccharificable material (w/w). Mathematic surface response analysis of the acid
      and enzymatic BAT hydrolysis was used for process optimization. The results
      showed a satisfactory correlation (R (2) = 0.90) between the obtained and
      predicted responses. The native yeast Pichia caribbica UM-5 was used to ferment
      sugar liquors from both acid and enzymatic hydrolysis to ethanol yielding 50 and
      87%, respectively. The final optimized process generated 8.99 g ethanol/50 g of
      BAT, corresponding to an overall 56.75% of theoretical ethanol (w/w). Thus, BAT
      may be employed as a lignocellulosic raw material for bioethanol production and
      can contribute to BAT residue elimination from environment.

PMID- 21072558
TI  - The plasma and cerebrospinal fluid pharmacokinetics of sorafenib after
      intravenous administration in non-human primates.
AB  - PURPOSE: Sorafenib is a small molecule inhibitor of multiple signaling kinases
      thought to contribute to the pathogenesis of many tumors including brain tumors.
      Clinical trials with sorafenib in primary and metastatic brain tumors are
      ongoing. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics
      (PK) of sorafenib after an intravenous (IV) dose in a non-human primate (NHP)
      model. METHODS: 7.3 mg/kg of sorafenib free base equivalent solubilized in 20%
      cyclodextrin was administered IV over 1 h to three adult rhesus monkeys. Serial
      paired plasma and CSF samples were collected over 24 h. Sorafenib was quantified
      with a validated HPLC/tandem mass spectrometry assay. PK parameters were
      estimated using non-compartmental methods. CSF penetration was calculated from
      the AUC(CSF) : AUC(plasma). RESULTS: Peak plasma concentrations after IV dosing
      ranged from 3.4 to 7.6 MUg/mL. The mean +/- standard deviation (SD) area under
      the plasma concentration from 0 to 24 h was 28 +/- 4.3 MUg * h/mL, which is
      comparable to the exposure observed in humans at recommended doses. The mean +/-
      SD clearance was 1.7 +/- 0.5 mL/min/kg. The peak CSF concentrations ranged from
      0.00045 to 0.00058 MUg/mL. The mean +/- SD area under the CSF concentration from
      0 to 24h was 0.0048 +/- 0.0016 MUg*h/mL. The mean CSF penetration of sorafenib
      was 0.02% and 3.4% after correcting for plasma protein binding. CONCLUSION:
      Sorafenib is well tolerated in NHP and measurable in CSF after an IV dose. The
      CSF penetration of sorafenib is limited relative to total and free drug exposure
      in plasma.

PMID- 21072559
TI  - Enzymatic synthesis of sucrose octaacetate using a novel alkaline protease.
AB  - Acylation of 0.5 g sucrose with 1.2 ml acetic anhydride was carried out in 2 ml
      two-solvent medium of anhydrous pyridine/n-hexane (1:1, v/v) using 0.2 g crude
      protease from Serratia sp. Sucrose octaacetate was the sole product and more than
      90% sucrose was converted in 24 h at 30 degrees C. The purity of sucrose
      octaacetate reached 100%, via a simple purification method of alcohol/water
      washing and centrifugation.

PMID- 21072560
TI  - Construction and evaluation of shuttle vector, pGYC4alpha, based on pYC2 from
      Lactobacillus sakei.
AB  - The shuttle vector pGYC4alpha (6,157 bp) was constructed based on the sigma
      replicon plasmid pYC2 from Lactobacillus sakei BM5 isolated from kimchi. The
      vector contained inserts of the ColE1 replicon, alpha-amylase gene from Bacillus
      licheniformis containing its own signal peptide, and lactococcal promoter P32.
      Transformation and expression of a selection marker gene (alpha-amylase) with
      pGYC4alpha were demonstrated in Escherichia coli and several lactic acid bacteria
      (LAB). The highest alpha-amylase activity in LAB transformants was obtained in
      M17/0.25% glucose media with 0.5% CaCO(3). The segregational stability of the
      shuttle vector in LAB was 100% for more than 100 generations in the absence of
      antibiotic pressure. The developed vector might be useful as a genetic tool for
      food industries.

PMID- 21072561
TI  - Fast filtration for metabolome sampling of suspended animal cells.
AB  - A new method for sampling suspended animal cells by fast filtration is presented
      that allows rapid quenching of cellular metabolism and efficient separation of
      the cells from culture medium. Compared to sampling with a microstructure heat
      exchanger or centrifugation without prior quenching, the adenylate energy charge
      and the measured concentrations especially of metabolites with a high turnover
      rate or of metabolites early in metabolic pathways were substantially higher. No
      leakage of ATP from the cells was observed when using iso-osmotic NaCl solution
      in the washing step. The combination of fast filtration and cold methanol
      extraction is therefore suitable for intracellular metabolomic studies of
      suspended animal cell cultures and superior to other methods currently applied.

PMID- 21072562
TI  - Induction of apoptosis in human colon carcinoma COLO 205 cells by the recombinant
      alpha subunit of C-phycocyanin.
AB  - The alpha-subunit of C-phycocyanin (CpcA) was expressed in Escherichia coli and
      purified. The recombinant CpcA inhibited the growth of human colon carcinoma COLO
      205 cells. Typical apoptotic morphological characteristics, such as chromatin
      condensation and nuclear fragmentation, were observed in CpcA-treated COLO 205
      cells by fluorescence microscopy and transmission electron microscopy. Moreover,
      the apoptotic process was associated with the Bax/Bcl-2 ratio up-regulation,
      mitochondrial membrane depolarization, cytochrome c release, and caspase-9
      activation. These findings indicate that CpcA induced the death of COLO 205 cells
      through the intrinsic apoptotic pathway.

PMID- 21072563
TI  - Cloning and analysis of the xylAB operon and characterization of xylose isomerase
      from Thermoanaerobacter ethanolicus.
AB  - Three genes, xylA-like, xylA and xylB, were cloned and sequenced from the
      chromosome of Thermoanaerobacter ethanolicus JW200. xylA and xylB share an operon
      and encode xylose isomerase and xylulokinase, respectively. The xylA-like gene
      locates upstream of xylAB operon and encodes a hypothetical protein that lacks
      xylose isomerase activity. The xylose isomerase was expressed in Escherichia coli
      and purified by heat treatment and an ion-exchange chromatography. The enzyme had
      highest activity at 85 degrees C and pH 7.0, and a half-life for 1 h at 85
      degrees C. The K (m) and V (max) values for xylose were 11 mM and 25 U/mg,
      respectively. The high level of expression, easy purification, and
      thermostability of the XylA from T. ethanolicus JW200 suggests industrial
      usefulness.

PMID- 21072564
TI  - Expression of the hIGF-I gene driven by the Fhx/P25 promoter in the silk glands
      of germline silkworm and transformed BmN cells.
AB  - The expression of the human insulin-like growth factor (hIGF-I) gene driven by
      the Fhx/P25 promoter in the silk glands of transgenic silkworms (Bombyx mori) and
      in transformed silkworm cells, was achieved using BmN cells transfected with a
      piggyBac vector, pigA3GFP-Fhx/P25-hIGF-ie-neo containing a neomycin-resistance
      gene (neo), a green fluorescent protein gene (gfp), an hIGF-I gene, and a helper
      plasmid containing the piggyBac transposase sequence under the control of the B.
      mori actin 3 (A3) promoter. We selected stably transformed BmN cells expressing
      hIGF-I using the antibiotic G418. The expression level of hIGF-I was about 450 pg
      in 3 * 10(6) cells, determined by ELISA. The piggyBac vector was transferred into
      the silkworm eggs using sperm-mediated gene transfer. The expression level of
      hIGF-I per gram fresh posterior silk glands of G4 transgenic silkworms was
      approx. 150 ng.

PMID- 21072565
TI  - Molecular characterization and evolution of an interspersed repetitive DNA family
      of oysters.
AB  - When genomic DNA from the European flat oyster Ostrea edulis L. was digested by
      BclI enzyme, a band of about 150 bp was observed in agarose gel. After cloning
      and sequencing this band and analysing their molecular characteristics and
      genomic organization by means of Southern blot, in situ hybridisation, and
      polymerase chain reaction (PCR) protocols, we concluded that this band is an
      interspersed highly repeated DNA element, which is related in sequence to the
      flanking regions of (CT)-microsatellite loci of the species O. edulis and
      Crassostrea gigas. Furthermore, we determined that this element forms part of a
      longer repetitive unit of 268 bp in length that, at least in some loci, is
      present in more than one copy. By Southern blot hybridisation and PCR
      amplifications-using primers designed for conserved regions of the 150-bp BclI
      clones of O. edulis-we determined that this repetitive DNA family is conserved in
      five other oyster species (O. stentina, C. angulata, C. gigas, C. ariakensis, and
      C. sikamea) while it is apparently absent in C. gasar. Finally, based on the
      analysis of the repetitive units in these oyster species, we discuss the slow
      degree of concerted evolution in this interspersed repetitive DNA family and its
      use for phylogenetic analysis.

PMID- 21072566
TI  - The library model for satellite DNA evolution: a case study with the rodents of
      the genus Ctenomys (Octodontidae) from the Ibera marsh, Argentina.
AB  - On the basement of the library model of satellite DNA evolution is the
      differential amplification of subfamilies through lineages diversification.
      However, this idea has rarely been explored from an experimental point of view.
      In the present work, we analyzed copy number and sequence variability of RPCS
      (repetitive PvuII Ctenomys sequence), the major satellite DNA present in the
      genomes of the rodents of the genus Ctenomys, in a closely related group of
      species and forms inhabiting the Ibera marsh in Argentina. We studied the
      dependence of these two parameters at the intrapopulation level because in the
      case of interbreeding genomes, differences in RPCS copy number are due to recent
      amplification/contraction events. We found an inverse relationship among RPCS
      copy number and sequence variability: amplifications lead to a decrease in
      sequence variability, by means of biased homogenization of the overall satellite
      DNA, prevailing few variants. On the contrary, the contraction events that
      involve tandems of homogeneous monomers contribute-by default-minor variants to
      become "evident", which otherwise were undetectable. On the other hand, all the
      RPCS sequence variants are totally or partially shared by all the studied
      populations. As a whole, these results are comprehensible if these RPCS variants
      preexisted in the common ancestor of this Ctenomys group.

PMID- 21072567
TI  - Mosaicism may explain the evolution of social characters in haplodiploid
      Hymenoptera with female workers.
AB  - The role of haplodiploidy in the evolution of eusocial insects and why in
      Hymenoptera males do not perform any work is presently unknown. We show here that
      within-colony conflict caused by the coexistence of individuals of the same caste
      expressing the same character in different ways can be fundamental in the
      evolution of social characters in species that have already reached the eusocial
      condition. Mosaic colonies, composed by individuals expressing either the wild
      type or a mutant phenotype, inevitably occurs during the evolution of
      advantageous social traits in insects. We simulated the evolution of an
      advantageous social trait increasing colony fitness in haplodiploid and
      diplodiploid species considering all possible conditions, i.e.
      dominance/recessivity of the allele determining the new social character, sex of
      the castes, and influence of mosaicism on the colony fitness. When mosaicism
      lowered colony fitness below that of the colony homogeneous for the wild type
      allele, the fixation of an advantageous social character was possible only in
      haplodiploids with female castes. When mosaicism caused smaller reductions in
      colony fitness, reaching frequencies of 90% was much faster in haplodiploids with
      female castes and dominant mutations. Our results suggest that the evolution of
      social characters is easier in haplodiploid than in diplodiploid species,
      provided that workers are females.

PMID- 21072568
TI  - Relative extraction ratio (RER) for arsenic and heavy metals in soils and
      tailings from various metal mines, Korea.
AB  - This study focused on the evaluation of leaching behaviours for arsenic and heavy
      metals (Cd, Cu, Ni, Pb and Zn) in soils and tailings contaminated by mining
      activities. Ten representative mine soils were taken at four representative metal
      mines in Korea. To evaluate the leaching characteristics of the samples, eight
      extraction methods were adapted namely 0.1 M HCl, 0.5 M HCl, 1.0 M HCl, 3.0 M
      HCl, Korean Standard Leaching Procedure for waste materials (KSLP), Synthetic
      Precipitation Leaching Procedure (SPLP), Toxicity Characteristic Leaching
      Procedure (TCLP) and aqua regia extraction (AR) methods. In order to compare
      element concentrations as extraction methods, relative extraction ratios (RERs,
      %), defined as element concentration extracted by the individual leaching method
      divided by that extracted by aqua regia based on USEPA method 3050B, were
      calculated. Although the RER values can vary upon sample types and elements, they
      increase with increasing ionic strength of each extracting solution. Thus, the
      RER for arsenic and heavy metals in the samples increased in the order of KSLP <
      SPLP < TCLP < 0.1 M HCl < 0.5 M HCl < 1.0 M HCl < 3.0 M HCl. In the same
      extraction method, the RER values for Cd and Zn were relatively higher than those
      for As, Cu, Ni and Pb. This may be due to differences in geochemical behaviour of
      each element, namely high solubility of Cd and Zn and low solubility of As, Cu,
      Ni and Pb in surface environment. Thus, the extraction results can give important
      information on the degree and extent of arsenic and heavy metal dispersion in the
      surface environment.

PMID- 21072570
TI  - Clarifying the identity of Amblyseius swirskii and Amblyseius rykei (Acari:
      Phytoseiidae): are they two distinct species or two populations of one species?
AB  - The generalist predator Amblyseius swirskii is an efficient natural enemy of
      small insects and phytophagous mites, particularly thrips and spider mites. This
      phytoseiid species was considered for a long time as a subtropical species and
      Amblyseius rykei as a sub-Saharan African species. A recent revision of
      phytoseiid species of the subtribe Amblyseiina from sub-Saharan Africa Zannou et
      al. (Zootaxa 1550:1-47, 2007) determined that the two species are identical and
      synonymized them. To confirm or invalidate that morphological study, we crossed a
      Benin population of A. rykei and an Israel population of A. swirskii through two
      generations and back-crossed their hybrids to their parents. We also compared
      demographic parameters of both species on maize pollen, and their predation and
      oviposition rates on first larval instars of Frankliniella occidentalis. All
      females of homogamic and heterogamic crosses produced viable progeny, fertile F1
      and viable F2. All the laid eggs hatched and sex ratio was female-biased for all
      crosses. Demographic parameters of the two species on maize pollen, and their
      predation rates and development times (egg to adult) on first instars of F.
      occidentalis were similar. Only oviposition of A. swirskii on larvae of F.
      occidentalis was significantly higher than that of A. rykei. These results
      indicate that A. rykei and A. swirkii are conspecific, and thus are a single
      species as concluded by Zannou et al.

PMID- 21072569
TI  - Alkaline degradation study of linear and network poly(epsilon-caprolactone).
AB  - Alkaline hydrolysis of a polycaprolactone (PCL) network obtained by
      photopolymerization of a PCL macromer was investigated. The PCL macromer was
      obtained by the reaction of PCL diol with methacrylic anhydride. Degradation of
      PCL network is much faster than linear PCL; the weight loss rate is approximately
      constant until it reaches around 70%, which happens after approximately 60 h in
      PCL network and 600 h in linear PCL. Calorimetric results show no changes in
      crystallinity throughout degradation, suggesting that it takes place in the
      crystalline and amorphous phases simultaneously. Scanning electron microscopy
      microphotographs indicate that degradation is produced by a different erosion
      mechanism in both kinds of samples. The more hydrophilic network PCL would follow
      a bulk-erosion mechanism, whereas linear PCL would follow a surface-erosion
      mechanism. Mechanical testing of degraded samples shows a decline in mechanical
      properties due to changes in sample porosity as a consequence of the degradation
      process.

PMID- 21072571
TI  - Accelerated stability studies for moisture-induced aggregation of tetanus toxoid.
AB  - PURPOSE: The study was carried out to evaluate the effect of exposing solid
      tetanus toxoid to moisture in two different ways on the structure and function of
      the toxoid. METHODS: Tetanus toxoid was exposed to moisture by (i) the addition
      of an optimized amount of buffer and (ii) incubation under an environment
      provided by a saturated solution of K(2)CrO(4.) The changes in the
      conformational, structural and antigenic properties of tetanus toxoid were
      measured and compared. RESULTS: Results show that even at a similar level of
      moisture-induced aggregation, the amounts of water absorbed by the two
      preparations of tetanus toxoid are different. Differences in antigenicity and
      changes in structure of the toxoid at primary, secondary and tertiary structure
      levels were seen. CONCLUSION: Although both conditions are used to mimic
      accelerated stability conditions in the laboratory, the final products are
      different in the two cases. Thus, conditions for 'accelerated stability studies'
      for therapeutic proteins need to be selected with care so that they resemble the
      fate of the actual product.

PMID- 21072572
TI  - beta-cyclocitral, a grazer defence signal unique to the cyanobacterium
      Microcystis.
AB  - beta-Cyclocitral is often present in eutrophic waters and is a well known source
      of airborne and drinking water malodor, but its production and functional ecology
      are unresolved. This volatile organic compound (VOC) is derived from the
      catalytic breakdown of beta-carotene, and evidence indicates that it is produced
      by the activation of a specific carotene oxygenase by all species of the bloom
      forming cyanobacterium Microcystis. Previous work has shown that beta-cyclocitral
      affects grazer behavior, but the nature of this interaction and its influence on
      predator-prey dynamics was unresolved. The present study combined analytical and
      behavioral studies to evaluate this interaction by using Microcystis NRC-1 and
      Daphnia magna. Results showed that beta-cyclocitral was undetectable in live
      Microcystis cells, or present only at extremely low concentrations (2.6 amol
      /cell). In contrast, cell rupture activated a rapid carotene oxygenase reaction,
      which produced high amounts (77 +/- 5.5 amol beta-cyclocitral/cell),
      corresponding to a calculated maximum intracellular concentration of 2.2 mM. The
      behavioral response of Daphnia magna to beta-cyclocitral was evaluated in a
      bbe(c) Daphnia toximeter, where beta-cyclocitral treatments induced a marked
      increase in swimming velocity. Acclimation took place within a few minutes, when
      Daphnia returned to normal swimming velocity while still exposed to beta
      cyclocitral. The minimum VOC concentration (odor threshold) that elicited a
      significant grazer response was 750 nM beta-cyclocitral, some 2,900 times lower
      than the per capita yield of a growing Microcystis cell after activation. Under
      natural conditions, initial grazer-related or other mode of cell rupture would
      lead to the development of a robust beta-cyclocitral microzone around Microcystis
      colonies, thus acting as both a powerful repellent and signal of poor quality
      food to grazers.

PMID- 21072573
TI  - Antifungal abietane-type diterpenes from the cones of Taxodium distichum Rich.
AB  - The chemical composition of Taxodium distichum cones and the antifungal
      activities of twelve diterpenoids against two wood decay fungi, Trametes
      versicolor (white-rot) and Fomitopsis palustris (brown-rot) were examined. The
      chemical composition of the major extractive fraction, the n-C(6)H(14) extract,
      was evaluated and its antifungal properties were identified. Twelve diterpenoids
      including ten abietane-type components were isolated from the n-C(6)H(14)
      extract: 6,7-dehydroferruginol (1), ferruginol (2), 6,7-dehydroroyleanone (3),
      sandaracopimaric acid (4), taxodione (5), taxodal (6), taxodone (7), sugiol (8),
      xanthoperol (9), salvinolone (10), 5,6-dehydrosugiol (11), and 14-deoxycoleon U
      (12). Compounds 5 and 12 were highly active against both wood-decay fungi. In
      particular, the activities of these compounds against F. palustris were potent.
      The results suggest that the position and the number of hydroxyl groups on
      abietane-type structures may be related to antifungal activities against T.
      versicolor and F. palustris.

PMID- 21072574
TI  - Performance measurement in the health sector: uses of frontier efficiency
      methodologies and multi-criteria decision making.

PMID- 21072575
TI  - VDAC contributes to mRNA levels in Saccharomyces cerevisiae cells by the
      intracellular reduction/oxidation state dependent and independent mechanisms.
AB  - Available data suggest that voltage-dependent anion selective channel (VDAC)
      constitutes an important component of a cellular regulatory mechanism based on
      the intracellular reduction/oxidation (redox) state. Here, using quantitative RT
      PCR, we demonstrated that depletion of VDAC1 (termed here VDAC) in Saccharomyces
      cerevisiae cells distinctly affected levels of mRNAs encoding nuclear proteins
      sensitive to changes of the intracellular redox state including the nuclear
      transcription factors important for adaptation to the redox state and proteins
      involved in communication between mitochondria and the nucleus. We also revealed
      that the changes of the studied protein transcript levels generally correlated
      with changes of the intracellular redox state although VDAC appears also to
      affect mRNA levels by a mechanism not based on changes of the intracellular redox
      states. Thus, VDAC seems to be an important element of the intracellular
      signaling network.

PMID- 21072577
TI  - Is it time to change the stereotype of cancer: the expert view.
AB  - OBJECTIVES: Negative public attitudes towards cancer may contribute to delays in
      presentation and present barriers to providing quality care. This study explored
      the views of cancer experts regarding the content of public health messages to
      improve public attitudes to cancer. METHODS: Twenty-one healthcare professionals
      (HCPs) from a range of backgrounds took part took part in interviews. Interview
      transcripts were evaluated using thematic analysis focusing on the HCPs views of
      the prevailing negative stereotype of cancer patients and their recommendations
      for cancer awareness campaigns that could redress this view. RESULTS: HCPs
      contrasted the progress that had been made in the effective management of cancer
      with popular stereotypes and media representations. Information quality and
      supply were identified as barriers to changing the cancer stereotype held by the
      public. CONCLUSIONS: HCPs believe there is a need for more information about
      cancer in the public domain and it should focus on providing more balanced
      messages that include information about the improvements that have been achieved
      in preventing and treating cancer.

PMID- 21072576
TI  - Ovariectomy alters energy metabolism in rat striatum: effect of supplementation
      with soy diet rich in isoflavones.
AB  - In the present study we investigated the effect of ovariectomy on some parameters
      of energy metabolism, namely Na(+),K(+)-ATPase and pyruvate kinase activities, as
      well as the mitochondrial respiratory chain enzymes activities succinate
      dehydrogenase, complex II and cytochrome c oxidase in rat striatum. The influence
      of soy diet rich in isoflavones on the effects elicited by ovariectomy on enzyme
      activities was also evaluated. Female adult Wistar rats were assigned to one of
      the following groups: sham (submitted to surgery without removal of the ovaries)
      and ovariectomized. Seven days after surgery animals were fed for 30 days on a
      special diet with soy protein or a standard diet with casein (control). Rats were
      sacrificed after treatment and the striatum was dissected. Results showed that
      rats subjected to ovariectomy presented a significant increase in Na(+),K(+)
      ATPase, succinate dehydrogenase and complex II activities. Treatment with
      isoflavones-rich soy diet was able to reverse the increase of Na(+),K(+)-ATPase
      activity, but was not effective in reversing the changes caused by ovariectomy on
      succinate dehydrogenase and complex II activities. Since ovariectomy mimics
      postmenopausal changes, our findings suggest that dysfunction of brain energy
      metabolism may be related to neurological symptoms observed in some
      postmenopausal women.

PMID- 21072578
TI  - Vitamin D, calcium, and retinol intake, and pancreatic cancer in a population
      based case-control study in the San Francisco Bay area.
AB  - OBJECTIVE: The aim of this study was to evaluate a complex association among
      intake of dietary vitamin D, calcium, and retinol, and pancreatic cancer risk.
      METHODS: Pancreatic cancer cases (n = 532) diagnosed in 1995-1999 were identified
      using rapid case ascertainment methods and were frequency matched to population
      based controls (n = 1,701) in the San Francisco Bay Area. Detailed dietary data
      were collected during in-person interviews using a validated semi-quantitative
      food-frequency questionnaire. Adjusted unconditional logistic regression was used
      to estimate odds ratios (ORs) and confidence intervals. RESULTS: In men,
      increased pancreatic cancer risk was associated with currently recommended
      dietary vitamin D intake levels (highest (>=450 IU/day) vs. lowest (<150 IU/day)
      intake, OR = 2.6, trend-p = 0.009) and total vitamin D intake from diet and
      supplements (for <800 IU/day). ORs for dietary vitamin D intake remained
      increased after adjustment for intake of retinol and calcium, although confidence
      intervals included unity. Stratified analyses showed that ORs were higher among
      men with lower intake of retinol and lower physical activity but there was no
      evidence of statistical interaction. No associations with vitamin D intake were
      observed among women, although ORs typically were elevated. ORs increased with
      increased dietary calcium intake among men (trend-p = 0.008) and not women.
      CONCLUSIONS: Our results among men showing an increased risk of pancreatic cancer
      associated with dietary intake of vitamin D and of calcium require confirmation
      in further studies. Continued investigation is needed to clarify the complex role
      of vitamin D and calcium in pancreatic cancer risk and to determine their optimal
      intake level and preventive effects for pancreatic cancer.

PMID- 21072580
TI  - In conclusion: looking to the future of comprehensive cancer control.
AB  - The articles in this monograph illustrate the progress and successes of
      comprehensive cancer control (CCC) since our 2005 publication. The strides made
      in CCC demonstrate the energy and commitment of this nationwide movement to
      reduce the burden of cancer for all people. The purpose of this conclusion paper
      is to discuss the future of CCC, which promises a new emphasis on policy, primary
      prevention, public health, evidence-based interventions, and global health
      supported by advanced communication tools.

PMID- 21072579
TI  - Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung:
      pooled analysis of seven case-control studies in the International Lung Cancer
      Consortium (ILCCO).
AB  - BACKGROUND: The International Lung Cancer Consortium (ILCCO) was established in
      2004, based on the collaboration of research groups leading large molecular
      epidemiology studies of lung cancer that are ongoing or have been recently
      completed. This framework offered the opportunity to investigate the role of
      tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare
      form of lung cancer. METHODS: Our pooled data comprised seven case-control
      studies from the United States, with detailed information on tobacco smoking and
      histology, which contributed 799 cases of BAC and 15,859 controls. We estimated
      the odds ratio of BAC for tobacco smoking, using never smokers as a referent
      category, after adjustment for age, sex, race, and study center. RESULTS: The
      odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08,
      2.93); the risk increased linearly with duration, amount, and cumulative
      cigarette smoking and persisted long after smoking cessation. The proportion of
      BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54). CONCLUSIONS: This
      analysis provides a precise estimate of the risk of BAC for tobacco smoking.

PMID- 21072581
TI  - Increased expression of TNF receptor-associated factor 6 after rat traumatic
      brain injury.
AB  - TRAF6 (TNF receptor-associated factor 6), a member of tumor necrosis factor
      receptor-associated factors family was identified as a molecule that binds to the
      cytoplasmic domain of CD40. TRAF6 functions as an adaptor, positively regulating
      the NF-kappaB, JNK pathway. Additionally, some studies have reported that TRAF6
      is required for apoptosis within the developing CNS and regulates cell fate
      decisions by inducing caspase 8-dependent apoptosis. However, its distribution
      and function in the central nervous system (CNS) lesion are not well understood.
      In this study, we performed an acute traumatic brain injury model in adult rats.
      And we mainly examined protein expression and cellular localization of TRAF6
      during rat traumatic brain injury (TBI). Western blot analysis showed TRAF6 level
      significantly improved at 7 days after injury, and then declined during the
      following days. The protein expression of TRAF6 was further analysed by
      immunohistochemistry. In comparison to contralateral cerebral cortex, we observed
      a highly significant accumulation of TRAF6 at the ipsilateral brain.
      Immunofluorescence double-labeling showed that TRAF6 was co-expressed with NeuN
      and GFAP. Besides, co-localization of TRAF6/active caspase 3 and
      TRAF6/proliferating cell nuclear antigen (PCNA) were detected in NeuN and GFAP,
      respectively. We also examined the expression profiles of proliferating cell
      nuclear antigen (PCNA) and active caspase 3 whose changes were correlated with
      the expression profiles of TRAF6. In conclusion, this is the first description of
      TRAF6 expression in traumatic brains. Our data suggested that TRAF6 might play
      important roles in CNS pathophysiology after TBI.

PMID- 21072583
TI  - Assessment of public exposure to naturally occurring radioactive materials from
      mining and mineral processing activities of Tarkwa Goldmine in Ghana.
AB  - Studies have been carried out in a Goldmine in Ghana to determine the exposure of
      the public to naturally occurring radioactive materials from processing of gold
      ore. Direct gamma spectrometry and neutron activation analysis techniques were
      used to analyse soil, rock, water and dust samples from the mining environment.
      The mean activity concentrations measured for (238)U, (232)Th and (40)K in the
      soil/rock samples were 15.2, 26.9 and 157.1 Bq kg( - 1), respectively. For the
      water samples, the mean activity concentrations were 0.54 and 0.41 Bq l( - 1))
      and 7.76 Bq l( - 1) for (226)Ra, (232)Th and (40)K, respectively. The mean
      activity concentrations measured in the dust samples were 4.90 and 2.75 MUBq m( -
      3) for (238)U and (232)Th, respectively. The total annual effective dose to the
      public was estimated to be 0.69 mSv. The results in this study compared well with
      typical world average values. The results indicate an insignificant exposure of
      the public from the activities of the Goldmine.

PMID- 21072582
TI  - Expression of vascular endothelial growth factor receptor-3 mRNA in the
      developing rat cerebellum.
AB  - Vascular endothelial growth factor receptor (VEGFR)-3, a receptor for VEGF-C and
      VEGF-D, has recently been suggested to play an important role during neuronal
      development. To characterize its potential role in CNS ontogenesis, we
      investigated the spatiotemporal and cellular expression of VEGFR-3 in developing
      and mature rat cerebellum using in situ hybridization. VEGFR-3 expression
      appeared as early as E15, and was restricted to the ventricular zone of the
      cerebellar primordium, the germinative neuroepithelium, but was absent by E20.
      Instead, the expression area of VEGFR-3 in the cerebellum grew in parallel with
      cerebellar development. From E20 on, two populations of VEGFR-3-expressing cells
      can be clearly distinguished in the developing cerebellum: a population of
      differentiating and postmitotic neurons and the Bergmann glia. VEGFR-3 expression
      in neurons occurred during the period of neuronal differentiation, and increased
      with maturation. In particular, the expression of VEGFR-3 mRNA revealed different
      temporal patterns in different neuronal populations. Neurons generated early,
      Purkinje cells, and deep nuclear neurons expressed VEGFR-3 mRNA during late
      embryonic stages, whereas VEGFR-3 transcription in local interneurons appeared by
      P14 with weaker expression. In addition, Bergmann glia expressed VEGFR-3
      throughout cerebellar maturation into adulthood. However, receptor expression was
      absent in the progenitors in the external granular layer and during further
      migration. The results of this study suggest that VEGFR-3 has even broader
      functions than previously thought, regulating both developmental processes and
      adult neuronal function in the cerebellum.

PMID- 21072584
TI  - The validation analysis of the INSHORE system--a precise and efficient coastal
      survey system.
AB  - Government and environmental entities are becoming increasingly concerned with
      qualifying and quantifying the erosion effects that are observed in sandy shores.
      Correspondingly, survey methodologies that gather data for such erosion studies
      are increasingly being demanded. The responsible entities are continually
      broadening their areas of interest, are concerned in the establishment of regular
      monitoring programmes and are demanding high accuracy from the geo-spatial data
      that is collected. The budget available for such monitoring activities, however,
      does not parallel the trend in the increasing demand for quality specifications.
      Survey methodologies need improvement to meet these requirements. We have
      developed a new land-based survey system--the INSHORE system--that is ideal for
      low cost, highly efficient and highly precise coastal surveys. The INSHORE system
      uses hi-tech hardware that is based on high-grade global positioning system (GPS)
      receivers and a laser distance sensor combined with advanced software algorithms.
      This system enables the determination of the ground coordinates of the surveyed
      areas with a precision of 1 to 2 cm, without having a sensor in contact with the
      ground surface. The absence of physical contact with the ground makes this system
      suitable for high-efficiency surveys. The accuracy of the positioning, which is
      based on advanced differential GPS processing, is enhanced by considering the
      estimated attitude of the GPS receiver holding structure and eliminates
      undesirable offsets. This paper describes the INSHORE survey system and presents
      the results of validation tests that were performed in a sandy shore environment.

PMID- 21072585
TI  - Decision-Tree-based data mining and rule induction for predicting and mapping
      soil bacterial diversity.
AB  - Soilmicrobial ecology plays a significant role in global ecosystems.
      Nevertheless, methods of model prediction and mapping have yet to be established
      for soil microbial ecology. The present study was undertaken to develop an
      artificial-intelligence- and geographical information system (GIS)-integrated
      framework for predicting and mapping soil bacterial diversity using pre-existing
      environmental geospatial database information, and to further evaluate the
      applicability of soil bacterial diversity mapping for planning construction of
      eco-friendly roads. Using a stratified random sampling, soil bacterial diversity
      was measured in 196 soil samples in a forest area where construction of an eco
      friendly road was planned. Model accuracy, coherence analyses, and tree analysis
      were systematically performed, and four-class discretized decision tree (DT) with
      ordinary pair-wise partitioning (OPP) was selected as the optimal model among
      tested five DT model variants. GIS-based simulations of the optimal DT model with
      varying weights assigned to soil ecological quality showed that the inclusion of
      soil ecology in environmental components, which are considered in environmental
      impact assessment, significantly affects the spatial distributions of overall
      environmental quality values as well as the determination of an environmentally
      optimized road route. This work suggests a guideline to use systematic accuracy,
      coherence, and tree analyses in selecting an optimal DT model from multiple
      candidate model variants, and demonstrates the applicability of the OPP-improved
      DT integrated with GIS in rule induction for mapping bacterial diversity. These
      findings also provide implication on the significance of soil microbial ecology
      in environmental impact assessment and eco-friendly construction planning.

PMID- 21072586
TI  - Land cover change of watersheds in Southern Guam from 1973 to 2001.
AB  - Land cover change can be caused by human-induced activities and natural forces.
      Land cover change in watershed level has been a main concern for a long time in
      the world since watersheds play an important role in our life and environment.
      This paper is focused on how to apply Landsat Multi-Spectral Scanner (MSS)
      satellite image of 1973 and Landsat Thematic Mapper (TM) satellite image of 2001
      to determine the land cover changes of coastal watersheds from 1973 to 2001. GIS
      and remote sensing are integrated to derive land cover information from Landsat
      satellite images of 1973 and 2001. The land cover classification is based on
      supervised classification method in remote sensing software ERDAS IMAGINE.
      Historical GIS data is used to replace the areas covered by clouds or shadows in
      the image of 1973 to improve classification accuracy. Then, temporal land cover
      is utilized to determine land cover change of coastal watersheds in southern
      Guam. The overall classification accuracies for Landsat MSS image of 1973 and
      Landsat TM image of 2001 are 82.74% and 90.42%, respectively. The overall
      classification of Landsat MSS image is particularly satisfactory considering its
      coarse spatial resolution and relatively bad data quality because of lots of
      clouds and shadows in the image. Watershed land cover change in southern Guam is
      affected greatly by anthropogenic activities. However, natural forces also affect
      land cover in space and time. Land cover information and change in watersheds can
      be applied for watershed management and planning, and environmental modeling and
      assessment. Based on spatio-temporal land cover information, the interaction
      behavior between human and environment may be evaluated. The findings in this
      research will be useful to similar research in other tropical islands.

PMID- 21072587
TI  - One century of hydrological monitoring in two small catchments with different
      forest coverage.
AB  - Long-term data on precipitation and runoff are essential to draw firm conclusions
      about the behavior and trends of hydrological catchments that may be influenced
      by land use and climate change. Here the longest continuous runoff records from
      small catchments (<1 km(2)) in Switzerland (and possibly worldwide) are reported.
      The history of the hydrological monitoring in the Sperbel- and Rappengraben
      (Emmental) is summarized, and inherent uncertainties in the data arising from the
      operation of the gauges are described. The runoff stations operated safely for
      more than 90% of the summer months when most of the major flood events occurred.
      Nevertheless, the absolute values of peak runoff during the largest flood events
      are subject to considerable uncertainty. The observed differences in average,
      base, and peak runoff can only partly be attributed to the substantial
      differences in forest coverage. This treasure trove of data can be used in
      various ways, exemplified here with an analysis of the generalized extreme value
      distributions of the two catchments. These distributions, and hence flood return
      periods, have varied greatly in the course of one century, influenced by the
      occurrence of single extreme events. The data will be made publicly available for
      the further analysis of the mechanisms governing the runoff behavior of small
      catchments, as well as for testing stochastic and deterministic models.

PMID- 21072588
TI  - Discriminating of HMG-CoA reductase inhibitors and decoys using self-organizing
      maps.
AB  - Self-Organizing Map (SOM) models were built to distinguish inhibitors of HMG-CoA
      reductase from its non-binding decoys. The molecules were represented by five
      global molecular descriptors and seven 2D property autocorrelation descriptors.
      Based on these molecular descriptors, 35 HMG-CoA reductase ligands and 1480
      decoys were projected into a self-organizing network. In the map, the ligands and
      the decoys were well separated, where no neuron was occupied by a ligand and a
      decoy at the same time. Afterward, the discriminating power of the selected
      molecular descriptors was further validated by extending the datasets to 135
      inhibitors. Finally, the SOM approach was subsequently used to identify active
      compounds in a virtual screening experiment by an external test set which
      included 32 HMG-CoA reductase inhibitors and 1103 decoys. In this study, 84.4% of
      the inhibitors (true positives) are retrieved with 15% contamination by non-hits
      (false positives). The SOM models obtained in this article exhibited powerful
      ability in virtual screening to find novel inhibitors for HMG-CoA reductase.

PMID- 21072589
TI  - A diversity-oriented synthesis of 3-(2-amino-1,6-dihydro-6-oxo-pyrimidin-5
      yl)propanoic esters.
AB  - The synthesis of dimethyl 2-(methoxymethylene) pentanedioates by an unusual
      Michael addition of 3,3-dimethoxypropionate to alpha, beta-unsaturated esters is
      described. These new intermediates can subsequently be converted to methyl 3-(2
      amino-1,6-dihydro-6-oxo-pyrimidin-5-yl)propanoates upon treatment with guanidine
      carbonate. The resulting pyrimidine derivatives are open-chain analogues of
      pyrido[2,3-d]pyrimidines with interesting biological activities.

PMID- 21072590
TI  - Novel and efficient one-pot five- and six-component reactions for the
      stereoselective synthesis of highly functionalized enaminones and
      dithiocarbamates.
AB  - Efficient methods for stereoselective synthesis of polyfunctional (E)-enaminones
      and (Z)-dithiocarbamates via one-pot five- and six-component sequential
      Ugi/Nucleophilic addition reactions are described. High yields and high bond
      forming efficiency, and simple operations are the advantages of this method.

PMID- 21072591
TI  - Effectiveness of doxazosin in the management of lower ureteral stones in male and
      female patients.
AB  - OBJECTIVES: To evaluate the effectiveness of doxazosin on the rate of spontaneous
      passage of distal ureteral stones in female patients. METHODS: A total of 80
      patients with stones sized 10 mm or smaller, located in the distal part of the
      ureter, were included. They were divided into two groups, according to the
      gender. Patients were followed-up until passage of the stone or for a maximum of
      3 weeks. The number of pain episodes, stone expulsion rate and time, and possible
      side effects of medications were recorded and compared in both groups. RESULTS:
      All patients completed the study. No statistically significant difference was
      observed regarding patient age, stone size, and stone location between the groups
      (P > 0.05). Stone expulsion occurred in 29 patients (72.5%) in group 1 and in 28
      patients (70%) in group 2 (P = 0.35). Mean time to expulsion was 6.5 days (range
      3-15 days) in the male arm and 7.5 days (range 4-17 days) in the female arm (P =
      0.97). There were no differences between the groups in the number of colic
      episodes and analgesic use. CONCLUSIONS: Medical treatment of distal ureteral
      stones with doxazosin has similar stone passage rate, expulsion time, and safety
      in women compared with men.

PMID- 21072592
TI  - Additive antitumoral effect of interleukin-12 gene therapy and chemotherapy in
      the treatment of urothelial bladder cancer in vitro and in vivo.
AB  - BACKGROUND: We evaluated antitumoral effect of combined chemotherapy and
      interleukin-12 (IL-12) gene therapy in in vitro and in vivo experimental
      urothelial bladder cancer (UBC) model. MATERIALS AND METHODS: EJ UBC cells were
      transfected with recombinant IL-12 genes using a liposomal transfection agent.
      Pirarubicin (THP) was added to the experimental samples at a final concentration
      of 20 mg/l. Four groups were assigned in vitro: untreated cells, transfected
      cells, untransfected cells plus THP and transfected cells plus THP. Death rates
      (DR) and cellular micromorphologic changes were evaluated. Bladder tumor model
      was established by subcutaneous injection of EJ cells to the nude mice. Four
      groups were assigned in vivo: control group; THP group; IL-12 gene group and IL
      12 gene plus THP group. After injection of combined THP and IL-12 gene therapy,
      tumor size and IL-12 levels were evaluated. RESULTS: In vitro study: DR in the
      THP + IL-12 gene therapy group (58.2 +/- 15.8%) was significantly higher than
      transfected group (12.2 +/- 5.6%; P = 0.01) and untransfected cells plus THP
      group (33.4 +/- 7.8; P = 0.046). A higher amount of apoptotic changes and
      necrosis on transmission electron microscope analysis were observed in
      transfected cells plus THP group. In vivo study: A significant tumor attenuation
      was found in IL-12 gene in combination with THP group when compared with any
      other groups that were treated without Il-12 or THP (P < 0.05). IL-12 levels in
      serum were significant high in IL-12 gene groups (P < 0.01). CONCLUSION: The
      combination of THP chemotherapy and IL-12 gene therapy showed an additive
      antitumoral effect on bladder cancer cells in vitro and in vivo. Further
      investigation should be focused on high-level transgene protocols in vivo.

PMID- 21072593
TI  - Dysfunction of the thick loop of Henle and senescence: from molecular biology to
      clinical geriatrics.
AB  - The sodium-potassium-2 chloride bumetanide-sensitive transporter (NKCC2), a
      protein coded by gene SLC12A1, allows salt reabsorption in the thick ascending
      loop of Henle (TALH). The functional and clinical exploration of the TALH can be
      carried out using the Chaimowitz's test, which is based on the exploration of the
      tubular response to an acute overload of a hypotonic sodium chloride solution.
      Since this segment is normally responsible for the generation of free water
      clearance, its function can be assessed via the calculation of such clearance
      from the parameters obtained during this test. By applying the Chaimowitz's test,
      the presence of incompetence for sodium reabsorption in TALH in healthy old
      people was documented. Additionally, it was documented that in water-restricted
      old rats, a situation that normally induces an increase in the number of NKCC2 in
      young rats is absent in old ones. In the clinical setting, the increased urinary
      sodium loss usually found in healthy old people predisposes them to dehydration,
      hypotension and or hyponatremia when they are on low-sodium diet or under
      treatment with diuretics. These are commonly found in elderly people with
      geriatric syndromes such as delirium, gait disorders and incontinence.
      CONCLUSION: The NKCC2 transporter decrease in the thick ascending loop of Henle
      secondary to the ageing could explain the reduced sodium reabsorption of this
      segment in the healthy elderly and its potential clinical consequences of
      dehydration and serum sodium abnormalities.

PMID- 21072594
TI  - Effects of intermittent electrical stimulation on superficial pressure, tissue
      oxygenation, and discomfort levels for the prevention of deep tissue injury.
AB  - The overall goal of this project is to develop effective methods for the
      prevention of deep tissue injury (DTI). DTI is a severe type of pressure ulcer
      that originates at deep bone-muscle interfaces as a result of the prolonged
      compression of tissue. It afflicts individuals with reduced mobility and
      sensation, particularly those with spinal cord injury. We previously proposed
      using a novel electrical stimulation paradigm called intermittent electrical
      stimulation (IES) for the prophylactic prevention of DTI. IES-induced
      contractions mimic the natural repositioning performed by intact individuals, who
      subconsciously reposition themselves as a result of discomfort due to prolonged
      sitting. In this study, we investigated the effectiveness of various IES
      paradigms in reducing pressure around the ischial tuberosities, increasing tissue
      oxygenation throughout the gluteus muscles, and reducing sitting discomfort in
      able-bodied volunteers. The results were compared to the effects of voluntary
      muscle contractions and conventional pressure relief maneuvers (wheelchair push
      ups). IES significantly reduced pressure around the tuberosities, produced
      significant and long-lasting elevations in tissue oxygenation, and significantly
      reduced discomfort produced by prolonged sitting. IES performed as well or better
      than both voluntary contractions and chair push-ups. The results suggest that IES
      may be an effective means for the prevention of DTI.

PMID- 21072595
TI  - Flow optimization study of a batch microfluidics PET tracer synthesizing device.
AB  - We present numerical modeling and experimental studies of flow optimization
      inside a batch microfluidic micro-reactor used for synthesis of human-scale doses
      of Positron Emission Tomography (PET) tracers. Novel techniques are used for
      mixing within, and eluting liquid out of, the coin-shaped reaction chamber.
      Numerical solutions of the general incompressible Navier Stokes equations along
      with time-dependent elution scalar field equation for the three dimensional coin
      shaped geometry were obtained and validated using fluorescence imaging analysis
      techniques. Utilizing the approach presented in this work, we were able to
      identify optimized geometrical and operational conditions for the micro-reactor
      in the absence of radioactive material commonly used in PET related tracer
      production platforms as well as evaluate the designed and fabricated micro
      reactor using numerical and experimental validations.

PMID- 21072597
TI  - Coding and traceability used by tissue banks in Mexico.
AB  - This short communication describes how some Mexican tissue banks have established
      their own system for coding and traceability of tissues.

PMID- 21072596
TI  - Analysis on the interaction between IL-1F7 gene and environmental factors on
      patients with ankylosing spondylitis: a case-only study.
AB  - To examine the interaction between IL-1F7 gene and environmental factors in
      patients with ankylosing spondylities (AS). 150 AS Han Chinese patients (all
      human leukocyte antigen-B27 positive) were genotyped using a panel of single
      nucleotide polymorphism markers within IL-1F7 gene (rs3811047) by ligase
      detection reactions. Polymerase chain reaction with sequence-specific primer was
      used to determine HLA-B27 subtypes. We analyzed the interaction between IF-1F7
      gene and eight environmental factors in AS patients by using a case-only study.
      The genetic polymorphism and environmental factors were considered as dependent
      variables in logistic models, and P-values, ORi and 95% confidence intervals were
      used for estimating the effects of interaction. The different frequency of A/G
      between drinking group and non-drinking group was significant (ORi 3.163, 95% CI
      1.368-7.317, P=0.006). Within the cooking oil group, odds ratio for interaction
      of G*E between main plants fats and half plants -half animal fats subunits was
      4.273 (95% CI 1.590-11.479, P=0.004). Our data show that there was no interaction
      between IL-1F7 alleles and the other six environmental factors in AS patients
      (all P>0.05). We observed that there was an interaction between IF-1F7 gene and
      drinking in AS patients. Thus, drinking may be a risk exposure factor to take
      combined action with predisposing genes in AS patients. This action may increase
      the incident risk of AS. Also, main plants fats may be protective factors to AS.

PMID- 21072598
TI  - International forum on tissue coding: response from South America, Uruguay.

PMID- 21072599
TI  - Lack of GNAQ germline mutations in uveal melanoma patients with high risk for
      hereditary cancer predisposition.
AB  - A high frequency of somatic mutation in GNAQ has been reported in uveal melanoma
      (UM). GNAQ is located in the chromosomal band 9q21, the same chromosomal band
      that harbors a putative candidate gene for hereditary UM. We investigated the
      frequency of germline sequence alterations in the GNAQ gene in UM patients with
      increased predisposition to hereditary cancer. A total of 44 high risk UM
      patients were studied including three patients with a family history of UM, 15
      patients with a family history of cutaneous melanoma (CM), three patients with
      early age at onset of their UM (<30 years) and 23 patients with strong family
      history of cancer and/or personal history of multiple primary tumors. Mutational
      screening of the seven exons of GNAQ and nearby intronic sequence was carried out
      by direct sequencing. We identified two deep intronic variants but no potential
      pathogenic mutations in GNAQ. Our results exclude GNAQ as a candidate gene in UM
      patients with a high risk for hereditary cancer predisposition.

PMID- 21072601
TI  - Integration of complementary and alternative medicine into medical schools in
      Austria, Germany and Switzerland--results of a cross-sectional study.
AB  - BACKGROUND: The results of a survey of decision makers (directors of clinical
      departments, along with research and education institutes) at German medical
      schools in 1997 demonstrated that although most respondents were in favour of
      integrating complementary and alternative medicine (CAM) into medical school
      curricula, only a minority had implemented these into their medical schools. The
      aims of this study were to evaluate the current opinions on CAM from decision
      makers at medical schools in three German-speaking countries and the present
      extent to which it has been integrated. METHODS: In 2004 we sent a standardised
      questionnaire to 1,017 department directors at medical schools in Austria (A, n =
      75), Germany (G, n = 873) and Switzerland (CH, n = 69). RESULTS: 487
      questionnaires (overall response rate: 48%, country-specific response rate: A
      39%; G 49%; S 42%) were returned. 40% of respondents had a positive opinion on
      CAM, whereas 28% had a neutral and 29% a negative opinion and 3% were unsure with
      a significant difference between Germany (44% positive opinion) in favour for CAM
      vs. Switzerland (22%; p = 0,021). The CAM therapies rated most positively were
      acupuncture (53%), osteopathy (52%) and naturopathy (38%) with no statistical
      differences between the countries. Naturopathy (39%) and herbal medicine (34%)
      were viewed more positively in Germany compared to Austria (4%, p = 0.001 and 8%,
      p = 0.01), but not to Switzerland (27%, p = 0.289 and 24%, p = 0.353). The
      majority of respondents favoured the integration of CAM into the medical system
      (research 85%, teaching 84% and treatment 60%). However, only 162 respondents
      (34%) indicated that CAM therapies had already been integrated into the
      curriculum at their medical schools (treatment 26%, research 19% and education
      18%) with no significant differences between the countries. Respondents of
      Switzerland indicated lower activity of CAM integration (treatment 10% and
      research 10%) compared to Austria (28%, p = 0.016 and 28%, p = 0.016) and Germany
      (27%, p = 0.01 and 20%, p = 0.174). CONCLUSIONS: The majority of respondents
      favoured the integration of CAM into the medical system. However, this
      integration remains limited and does not reflect the high usage of CAM in the
      population.

PMID- 21072600
TI  - Anti-inflammatory glucocorticoid drugs: reflections after 60 years.
AB  - This review considers the problem of the serious concomitant side effects of
      powerful anti-inflammatory drugs modelled upon the principal human glucocorticoid
      hormone, cortisol. The very nature of the original bio-assays to validate their
      cortisol-like hormonal and anti-inflammatory activities ensured that pleiotropic
      toxins were selected for clinical studies. Other complicating factors have been
      (1) considerable reliance on bio-assays conducted in laboratory animals that
      primarily secrete corticosterone, not cortisol, as their principal anti
      inflammatory adrenal hormone; (2) some differences in the binding of xenobiotic
      cortisol analogues (vis a vis cortisol) to transport proteins, detoxifying
      enzymes and even some intra-cellular receptors; (3) the "rogue" properties of
      these hormonal xenobiotics, acting independently of--but still able to suppress-
      hormonal mechanisms regulating endogenous cortisol; and (4) problems of
      intrinsic/acquired "steroid resistance", diminishing their clinical efficacy, but
      not necessarily all their toxicities. The rather gloomy conclusion is that
      devising new drugs to reproduce the effect of multi-potent hormones may be a
      recipe for disaster, in contexts other than simply remedying an endocrine
      deficiency. Promising new developments include "designed" combination therapies
      that allow some reduction in total steroid doses (and hopefully their side
      effects); sharpening strategies to limit the actual duration of steroid
      administration; and resurgent interest in searching for more selective analogues
      (both steroidal and non-steroid) with less harmful side effects. Some oversights
      and neglected areas of research are also considered. Overall, it now seems timely
      to engage in some drastic rethinking about (retaining?) these "licensed toxins"
      as fundamental therapies for chronic inflammation.

PMID- 21072602
TI  - Tobacco smoke load and non-lung cancer mortality associations in Austrian and
      German males.
AB  - The millstone around the neck of tobacco control in Europe has been the influence
      of the tobacco industry on the governments of German speaking countries. This
      study attempts to estimate non-lung cancer mortality attributable to smoking in
      Austria during 1967-2006 and in Germany during 1973-2006. National estimates of
      the annual smoking-attributable fractions (SAF) were calculated for all ages in
      males, using lung cancer mortality rates as indicators of "tobacco smoke load"
      associated with cancer from active and passive smoking. In both countries non
      lung cancer rates showed a nearly perfect linear correlation with lung cancer
      rates (R (2) = 0.95 in Austria and 0.94 in Germany) with a slope of 1.86 (95%
      confidence intervals [CI]: 1.71-1.99) in Austria and 1.77 (95% CI: 1.60-1.93) in
      Germany. In 2006 SAF of male cancer mortality for all ages were 61% in Austria
      (sensitivity range [SR]: 45%-70%) without autocorrelation and 61% in Germany (SR:
      41-75%), if adjusted for possible autocorrelation. The similarity of the results
      is in line with the poor tobacco control measures in both countries until
      recently. Cancer prevention programs in Austria and Germany should focus on
      tobacco control, because 61% of male cancer mortality was associated with tobacco
      smoke load.

PMID- 21072603
TI  - Cognitive function in elderly marathon runners: cross-sectional data from the
      marathon trial (APSOEM).
AB  - BACKGROUND: Cognitive impairment of the elderly contributes to morbidity, loss of
      quality of life, and impairment of work ability in aging western societies. Thus
      strategies to maintain cognitive function at an advanced age imply a great
      challenge to Occupational Medicine. AIM: To study whether intensive endurance
      exercise training is associated with better cognitive performance and increases
      brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF).
      METHODS: Active elderly marathon runners or bicyclists older than 60 years were
      recruited and matched with an inactive control group according to age, sex, and
      education years. After exclusion of various diseases according to the study
      protocol 56 athletes and 58 controls could be selected for follow-up studies. The
      influence of endurance training on cognitive function was assessed by the use of
      the Vienna Neuropsychological Test Battery and the CERAD test battery. Other
      relevant outcomes were the levels of BDNF, IGF-1, Apo e4 carrier state, and self
      ratings. RESULTS: The elderly marathon group performed better only in one
      specific cognitive task (the Five Point Test, p = 0.04) and almost significantly
      better in one additional test (the NAI Stroop Test, p = 0.08). Neither BDNF nor
      IGF-1 was related to the duration of daily exercise and no differences in the
      basal levels of these humoral growth factors in the exercise and the control
      cohort were found. Interestingly, we also found significantly decreased BDNF
      levels in subjects with Alzheimer's disease in the family in spite of the
      maintained normal cognitive performance (p = 0.01). CONCLUSION: These results
      suggest that extensive endurance exercise training might be beneficial for
      maintaining cognitive function in elderly persons. Our data demonstrate that
      beneficial endurance training effects are not linked to the upregulation of the
      examined neurotrophins. Since we found reduced BDNF-levels in subjects with a
      positive family history of Alzheimer's disease, we speculate that BDNF-reduction
      might precede cognitive impairment.

PMID- 21072605
TI  - Parry Romberg syndrome.

PMID- 21072604
TI  - Clinical consequences of the Calypso trial showing superiority of PEG-liposomal
      doxorubicin and carboplatin over paclitaxel and carboplatin in recurrent ovarian
      cancer: results of an Austrian gynecologic oncologists' expert meeting.
AB  - The Calypso trial showed an improved progression-free survival with PEG-liposomal
      doxorubicin (PLD) and carboplatin (P) as compared with the standard regimen
      paclitaxel (PCLTX) and P in the second- or third-line treatment of platinum
      sensitive epithelial ovarian cancer [1]. A panel of Austrian gynecologic
      oncologists discussed the clinical consequences of the data from the Calypso
      study for the routine practice. PLD + P had a significantly lower rate of
      alopecia and neuropathy than the taxane regimen, both toxicities which compromise
      the quality of life. Due to possible significant thrombocytopenia, the blood
      counts of patients undergoing PLD + P therapy should be monitored weekly.
      Patients receiving PLD/P are at higher risk of nausea and vomiting. Palmoplantar
      erythrodysesthesia (hand-foot syndrome) is a significant toxicity of PLD + P most
      prevalent after the third or fourth cycle. Prophylaxis consists of avoiding
      pressure on feet and hands and other parts of the body. Similarly, prophylaxis of
      mucositis seems important and includes avoiding consumption of hot, spicy and
      salty foods and drinks. Mouth dryness should be avoided. Premedication with
      antiemetics and dexamethasone dissolved in 5% glucose is done to prevent
      hypersensitivity to PLD. In conclusion, the therapeutic index is more favorable
      for PLD + P than for PCTX + P.

PMID- 21072606
TI  - ExploringMycobacterium tuberculosis infection-induced alterations in gene
      expression in macrophage by microarray hybridization.
AB  - Tuberculosis remains a serious threat to public health. Its causative
      agentMycobacterium tuberculosis is an intracellular pathogen which survives and
      replicates within cells of the host immune system, primarily macrophages.
      Knowledge of the bacteria-macrophage interaction can help to develop novel
      measures to combat the disease. The global gene expression of macrophage
      following invasion by and growth ofM. tuberculosis was studied by cDNA
      microarray. Of the 12800 human genes analyzed, totally 473 (3.7%) macrophage
      genes were differentially expressed after being infected byM. tuberculosis, among
      which, only 25 (5.2%, corresponding to less than 0.2% of the 12800 genes) genes
      were up-regulated, while others (94.8%) were down-regulated against the control.
      Of the 473 genes, 376 genes are registered in the GenBank, and 97 are novel
      genes. Expression of 5 up-regulated genes has been induced by more than 3-fold.
      25 genes were down-regulated by more than 3-fold. Syndecan binding protein has
      been down-regu- lated up to 12.5-fold. The data gave an insight into the early
      gene expression in macrophage ensuingM. tuberculosis infection and a basis for
      further study.

PMID- 21072607
TI  - Cloning of the promoter region of plasma membrane aquaporinBnPIP1 fromBrassica
      napus and its functional analysis.
AB  - A 1.6 kb upstream regulatory sequence (GenBank accession no. AF472487) of plasma
      membrane aquaporinBnPIP1 gene fromBrassica napus was obtained by genomic walking
      based on ligation-mediated PCR method. Sequence analysis indicated that this
      fragment contained seed germination specific and vascular specific sequences. The
      1.6 kb upstream sequence and various 5' end deleted sequences were fused withuidA
      gene and constructed into plant expression vectors which were used for tobacco
      transformation. GUS histochemical assay showed that the 1.6 kb fragment had high
      levels of promoter activity and the GUS staining was mainly distributed in
      vascular systems and tissues with rapid expanding and proliferating cells.
      Promoter deletion analysis showed that the deletion of -1610 - -1030 bp resulted
      in a dramatic reduction in GUS activity. It was assumed that there might be cis
      acting element(s) existing in this region. Whereas, the region located at -1030 -
      -902 bp strongly inhibited the expression ofgus and probably contained negative
      regulatory element(s). The fragment of -902 - -19 bp could also directgus
      expression at high level.

PMID- 21072608
TI  - Function of attention in learning process in the olfactory bulb.
AB  - It has been suggested that in the olfactory bulb, odor information is processed
      through parallel channels and learning depends on the cognitive environment. The
      synapse's spike effective time is defined as the effective time for a spike from
      pre-synapse to post-synapse, which varies with the type of synapse. A learning
      model of the olfactory bulb was constructed for synapses with varying spike
      effective times. The simulation results showed that such a model can realize the
      multi-channel processing of information in the bulb. Furthermore, the effect of
      the cognitive environment on the learning process was also studied. Different
      feedback frequencies were used to express different attention states. Considering
      the information's multi-channel processing requirement for learning, a learning
      rule considering both spike timing and average spike frequency is proposed.
      Simulation results showed that habituation and anti-habituation of an odor in the
      olfactory bulb might be the result of learning guided by a common local learning
      rule but at different attention states.

PMID- 21072609
TI  - Characterization of an ethylene receptor homolog gene from rice.
AB  - Ethylene plays important roles in plant growth, development and stress responses.
      Its receptor genes have been studied in dicots such asArabidopsis, tobacco and
      tomato. However, no research has been reported for the ethylene receptors from
      monocots currently. In the present study, we cloned an ethylene receptor
      geneOSPK2 from rice and found that its encoded protein was divergent from the
      ethylene receptors from dicots. OSPK2 had a long extension in its N-terminal,
      followed by three transmembrane segments, a GAF domain, a putative kinase domain
      and a putative receiver domain. Although most of the domains were conserved, the
      expected phosphorylation site His and the phosphate receiver Asp have been
      replaced by Gln and Asn, respectively. This fact indicates that OSPK2 may not
      function as a histidine kinase in a phosphorelay manner, but rather play roles by
      other mechanism, probably through Ser/Thr kinase activity. The expression of
      theOSPK2 gene was investigated by RT-PCR method under different conditions. We
      found that this gene was apparently induced by wounding and PEG treatment, but
      not significantly affected by salt and ABA treatments. The differential
      expression of theOSPK2 gene may reflect its roles in mediating different abiotic
      stress responses, consistent with our previous studies on tobacco ethylene
      receptors.

PMID- 21072610
TI  - Regulation of gelsolin to plant actin filaments and its distribution in pollen.
AB  - The effect of plasma gelsolin on plant microfilaments and its localization in
      plant cells were investigated. The results by using ultracentrifugation and
      electron microscopy showed that plant microfilaments could be severed into
      shorter fragments by gelsolin in a Ca(2+)-dependent manner. By measuring the
      binding ability of plasma gelsolin to pollen actin using the method of
      immunoprecipitation, it was shown that pollen actin could bind gelsolin at a
      ratio of 2.0+/-0.21 in the presence of Ca(2+). Addition of EGTA could
      disassociate the actin-gelsolin complexes, reducing the ratio to 1.2+/-0.23, and
      the addition of PIP(2) could further reduce the ratio to 0.8+/-0.1. The results
      indicate that plant actin has similar binding properties with plasma gelsolin as
      that of animal actin. By Western blotting we identified the existence of gelsolin
      in lily pollen. The results of immunolocalization of gelsolin in pollen and
      pollen tube showed that gelsolin was mainly localized at the germinal furrow in
      pollen grains and at the cytoplasm in pollen tube, especially in the tip region.

PMID- 21072611
TI  - Studies on gene structure, enzymatic activity and regulatory mechanism of
      acetohydroxy acid isomeroreductase from G2 pea.
AB  - TheAAIR genomic DNA of G2 pea (Pisum sativum L.) was amplified by PCR method.
      Sequence analysis showed that it was composed of 8 introns and 9 exons with three
      of the introns containing specific A/T-rich endogenous promoter regions.
      Molecular hybridization experiments revealed that the expression of AAIR remained
      at a high level before and after flowering if grown in short day growth chambers.
      However, when grown under long day conditions, the level of AAIR expression
      declined very rapidly after flowering. This variation of AAIR expression is
      consistent with the change of enzymatic activity of acetohydroxy acid
      isomeroreductase. Functional complementation experiments carried out using an
      acetohydroxy acid isomeroreductase deficientE. coli strain showed that these
      cells could not grow on M9 medium without addition of branched-chain amino acids
      unless they were transformed with theAAIR expression vector. Further study
      revealed that overexpression of the peaAAIR cDNA in acetohydroxy acid
      isomeroreductase deficientE. coli strain enhanced significantly its branched
      chain amino acid biosynthetic capacity. Results from gel shift experiments showed
      that fractions of pea nuclear protein extracts could bind specifically to some
      A/T rich regions present in introns of theAAIR gene. The A/T-rich-region-binding
      proteins remained at a steady level in the non-senescing apical buds of short-day
      grown G2 pea. In the rapid-senescing apical buds of long-day grown G2 pea, the
      levels of these proteins declined rapidly after flower initiation. Therefore, the
      nuclear protein binding capacities to endogenous promoter regions may constitute
      an important mechanism to regulateAAIR gene expression.

PMID- 21072612
TI  - Behavioral modification in choice process ofDrosophila.
AB  - In visual operant conditioning ofDrosophila at the flight simulator, only motor
      output of flies-yaw torque-is recorded, which is involved in the conditioning
      process. The current study used a newly-designed data analysis method to study
      the torque distribution ofDrosophila. Modification of torque distribution
      represents the effects of operant conditioning on flies' behavioral mode. Earlier
      works([10]) showed that, when facing contradictory visual cues, flies could make
      choices based upon the relative weightiness of different cues, and it was
      demonstrated that mushroom bodies might play an important role in such choice
      behavior. The new "torque-position map" method was used to explore the CS-US
      associative learning and choice behavior inDrosophila from the aspect of its
      behavioral mode. Finally, this work also discussed various possible neural bases
      involved in visual associative learning, choice processing and modification
      processing of the behavioral mode in the visual operant conditioning
      ofDrosophila.

PMID- 21072613
TI  - Chicken retinal ganglion cells response characteristics: multi-channel electrode
      recording study.
AB  - The first stage of visual processing occurs in the retina, the function of which
      is to process the raw information obtained from the outside world. In the present
      study, the electrical activities of a group of retinal ganglion cells were
      recorded from a small functioning piece of retina, using multi-electrode array
      (MEA), and the action potentials were detected by applying nonlinear algorithm.
      By analyzing the ensemble retinal ganglion output characteristics, it is revealed
      that both firing rates and correlated activity between adjacent neurons in the
      retina contribute to visual information encoding.

PMID- 21072614
TI  - Muscle injection of rAAV/mFIX to secrete clotting factor IX corrects the
      hemorrhagic tendencies in hemophilia B mice.
AB  - Recombinant AAV particles of high titer (>10(13) virus genome/mL) were prepared
      according to the rHSV/AAV helper virus method. After intramuscular injection of
      viral vectors in the hind limb, a sustained elevated level (>370 ng/mL) of murine
      FIX expression in the plasma of hemophilia B mouse was detected and persisted for
      more than 350 days. The biological activity reached 30% of normal levels, and
      bleeding symptoms in the treated mice were significantly alleviated. No anti-FIX
      antibody (inhibitor) was detected, though anti-AAV antibodies were found at a
      very low level after single injection. Repeated injection with rAAV/mFIX led to a
      variation in anti-AAV antibody levels between the two groups which had received
      different doses. Results from tissue analysis confirmed the skeletal muscle as
      the origin for circulating functional mFIX. Our results suggest that AAV-mediated
      gene transfer offers a promising method of gene therapy for hemophilia B.

PMID- 21072615
TI  - An efficient method of constructing homologous recom binant baculovirus with PCR
      amplified fragments.
AB  - This paper describes a rapid method of constructing homologous recombinant
      baculovirus inE. coli with PCR-amplified fragments. By using this method, the
      traditional steps of constructing transfer vector are omitted. The method is
      based on phage lambda red system which can promote the recombination between the
      homologous fragments with the length above 36 bp. Taking HaSNPV as an example,
      this paper describes the rapid recombination process by using chloramphenicol
      resistance gene (Cm ( R )) to replaceorf135 in HaSNPV genome. A pair of primers
      with length of 60 bp was synthesized, in which 40 bp was homologous to the each
      end sequence oforf135, and the rest 20 bp was homologous to the each end sequence
      ofCm ( R ). By using these primers, a linear fragment containing the completeCm (
      R ) gene between 40 bp of homologous arms oforf135 was generated by PCR with the
      plasmid pKD3 which containsCm ( R ) as the template. By transforming the linear
      fragment into theE. coli containing the bacterial artificial chromosome of HaSNPV
      and with the help of a plasmid expressing lambda recombinase, the recombinants on
      which the homologue replacement had taken place were selected by chloramphenicol
      resistance. This method greatly shortens the process of constructing recombinant
      baculovirus since the process was performed inE. coli and does not need to
      construct transfer vectors. It can be further used for gene replacement and gene
      deletion of other large viral genomes.

PMID- 21072616
TI  - Physiological characteristics of the primitive CO(2) concentrating mechanism in
      PEPC transgenic rice.
AB  - The relationship between carbon assimilation and high-level expression of the
      maize PEPC in PEPC transgenic rice was studied by comparison to that in the
      untransformed rice,japonica kitaake. Stomatal conductance and photosynthetic
      rates in PEPC transgenic rice were higher than those of untransformed rice, but
      the increase of stomatal conductance had no statistical correlation with that of
      photosynthetic rate. Under high levels of light intensity, the protein contents
      of PEPC and CA were increased significantly. Therefore the photosynthetic
      capacity was increased greatly (50%) with atmospheric CO(2) supply. While CO(2)
      release in leaf was reduced and the compensation point was lowered
      correspondingly under CO(2) free conditions. Treatment of the rice with the PEPC
      specific inhibitor DCDP showed that overexpression of PEPC and enhancement of
      carbon assimilation were related to the stability of Fv/Fm. Labeling
      with(14)CO(2) for 20 s showed more(14)C was distributed to C(4) primary
      photosynthate asperate in PEPC transgenic rice, suggesting that there exists a
      limiting C(4) photosynthetic mechanism in leaves. These results suggest that the
      primitive CO(2) concentrating mechanism found in rice could be reproduced through
      metabolic engineering, and shed light on the physiological basis for transgenic
      breeding with high photosynthetic efficiency.

PMID- 21072617
TI  - Vitamin B12 status, homocysteine and mortality amongst community-dwelling Irish
      elders.
AB  - BACKGROUND: Vitamin B12 deficiency is associated with hyperhomocysteinaemia,
      which is associated with atherosclerosis and increased mortality. High levels of
      vitamin B12 have also been associated with increased mortality in certain patient
      populations. AIMS: We examined vitamin B12 and homocysteine status and mortality
      rates in a population of Irish community-dwelling elders over a 3-year period.
      METHODS: Prospective, community-based observational cohort study. RESULTS:
      Subjects in the highest quartile of homocysteine had increased mortality rates
      (14.68 vs. 7.32%, relative risk 2.09). This relationship was attenuated when
      controlled for the presence or absence of a history of stroke or myocardial
      infarction. There was no relationship between vitamin B12 status and mortality
      during the observation period. CONCLUSION: Vitamin B12 levels are not associated
      with death rates in Irish community-dwelling elders. Homocysteine levels are
      associated with mortality and may act via the mechanism of atherosclerotic
      disease.

PMID- 21072618
TI  - Pneumococcal meningitis: clinical outcomes in a pre-vaccine era at a Dublin
      paediatric hospital, 1999-2007.
AB  - AIM: To document the long-term outcomes of pneumococcal meningitis in children
      presenting to a Dublin paediatric hospital in the pre-pneumococcal conjugate
      vaccine (PCV7) era (1998-2007). METHODS: Subjects with pneumococcal meningitis
      were identified at The Children's University Hospital, Dublin through the
      hospital surveillance system and laboratory archives. RESULTS: 44 children were
      identified with S. pneumoniae meningitis. Mean age of presentation was 23.45
      months (2 days to 13 years) and 28 (65%) cases were less than 12 months old.
      Eight (18.6%) children died. 55% of cases were left with significant deficits. Of
      the survivors, 7 (20%) had moderate to severe neurological sequelae. CONCLUSION:
      Pneumococcal meningitis is a devastating childhood disease with significant
      mortality and morbidity, especially in those less than 2 years of age. These data
      provide a baseline against which the impact of PCV7 on pneumococcal meningitis
      can be measured.

PMID- 21072619
TI  - Relaxin-3/INSL7 regulates the stress-response system in the rat hypothalamus.
AB  - Relaxin-3 (RLN3) is a neuropeptide belonging to the insulin-relaxin superfamily.
      RLN3-expressing neurons are predominantly located in the dorsal pons known as the
      nucleus incertus, and project their axons to the forebrain including the
      hypothalamus. RLN3 has been suggested to be involved in the stress response. In
      the present study, we investigated the hypothalamic action of RLN3 in the stress
      response system by intracerebroventricular (icv) administration of RLN3. Compared
      with saline icv injection, 1 nmol icv RLN3 injection induced c-Fos expression in
      the paraventricular nucleus of the hypothalamus (PVN) at 1 h after
      administration. Some RLN3-induced c-Fos-positive cells in the PVN were also
      corticotropin-releasing factor (CRF)-expressing neurons. CRF and c-fos mRNA
      levels in the PVN were increased at 2 h after RLN3 administration. Plasma
      adrenocorticotropic hormone (ACTH) levels were also increased after RLN3
      administration. These results suggest that RLN3 is able to stimulate the
      hypothalamopituitary CRF-ACTH system during the acute response.

PMID- 21072622
TI  - Neurolymphomatosis as a manifestation of relapsed primary cardiac lymphoma.

PMID- 21072620
TI  - Insulin analogues in the management of the pregnancy complicated by diabetes
      mellitus.
AB  - Since their introduction, insulin analogues are the preferred choice for short
      acting insulin due to their superior pharmacologic profiles, leading to greater
      flexibility and convenience of dosing and, thus, greater patient satisfaction and
      improved quality of life. Over the past few years, clinical experience with
      insulin analogues in pregnancy has increased. The most studied, insulin lispro,
      has been shown to be a safe and clinically effective option in the treatment of
      the diabetic gravida. Studies of the other insulin analogues are limited, but
      promising. Further research is warranted to evaluate safety and efficacy of these
      analogues.

PMID- 21072623
TI  - Successive cases of an entrapped arterial catheter guidewire in separate patients
      on the same day.

PMID- 21072624
TI  - Objective assessment of dermatitis following post-operative radiotherapy in
      patients with breast cancer treated with breast-conserving treatment.
AB  - PURPOSE: To evaluate radiation dermatitis objectively in patients with breast
      cancer who had undergone post-operative radiotherapy after breast-conserving
      surgery. PATIENTS AND METHODS: Skin color (L*, a*, and b* values) and moisture
      analyses were performed for both breasts (before, after, 1 month, 6 months, and 1
      year after radiotherapy) to examine irradiated and non-irradiated skin divided
      into four quadrants in 118 patients. These patients underwent breast conservative
      surgery followed by 50 Gy/25 fractions (median) of radiotherapy with or without
      boost irradiation (10 Gy/5 fractions). RESULTS: L*, a*, and moisture values were
      changed by irradiation and maximized at completion or 1 month after radiotherapy.
      One year after radiotherapy, the skin color had returned to the range observed
      prior to radiotherapy. However, moisture did not return to previous values even 1
      year after treatment. The lateral upper side (quadrant C) showed greater changes
      than other quadrants in the L* value (darker) at the end of radiotherapy. The
      Common Toxicity Criteria version 3 scores were found to correlate well with a*
      and L* values at the completion and 1 month after radiotherapy. Boost
      radiotherapy intensified reddish and darker color changes at the completion of
      radiotherapy, while chemotherapy did not intensify the skin reaction caused by
      radiotherapy. CONCLUSION: Moisture impairment as a result of irradiation lasts
      longer than color alterations. Objective assessments are useful for analyzing
      radiation dermatitis.

PMID- 21072625
TI  - Fibrotic changes after postmastectomy radiotherapy and reconstructive surgery in
      breast cancer. A retrospective analysis in 109 patients.
AB  - PURPOSE: The purpose of this study was to analyze the probability and time course
      of fibrotic changes in breast reconstruction before or after postmastectomy
      radiotherapy (PMRT). MATERIALS AND METHODS: Between 1995 and 2004, 109 patients
      were treated with PMRT at Tubingen University and underwent heterologous (HL) or
      autologous (AL) breast reconstruction prior or subsequent to radiation therapy.
      Fibrosis of the reconstructed breast after radiotherapy was assessed using the
      Baker score for HL reconstructions and the Common Terminology Criteria for
      Adverse Events (CTCAE) for all patients. Actuarial rates of fibrosis were
      calculated for the maximum degree acquired during follow- up and at the last
      follow-up visit documented. RESULTS: Median time to follow-up was 34 months (3
      227 months). Radiotherapy was applied with a median total dose of 50.4 Gy. A
      total of 44 patients (40.4%) received a boost treatment with a median dose of 10
      Gy. Breast reconstruction was performed with AL, HL, or combined techniques in
      20, 82, and 7 patients, respectively. The 3-year incidence of >= grade III
      maximum fibrosis was 20% and 43% for Baker and CTCAE scores, respectively. The
      corresponding figures for fibrosis at last follow-up visit were 18% and 2%. The 3
      year rate of surgical correction of the contralateral breast was 30%. Initially
      unplanned surgery of the reconstructed breast was performed in 39 patients
      (35.8%). Boost treatment and type of cosmetic surgery (HL vs. AL) were not
      significantly associated with the incidence of fibrosis. CONCLUSIONS: We found
      severe fibrosis to be a frequent complication after PMRT radiotherapy and breast
      reconstruction. However, surgical intervention can ameliorate the majority of
      high grade fibrotic events leading to acceptable long-term results. No treatment
      parameters associated with the rate of fibrosis could be identified.

PMID- 21072626
TI  - Design of small-molecule Smac mimetics as IAP antagonists.
AB  - Smac/DIABLO, discovered in 2000 as a protein released from mitochondria into the
      cytosol in response to apoptotic stimuli, functions as an endogenous antagonist
      of X-linked inhibitor of apoptosis protein (XIAP) and several other IAP proteins
      through direct binding. The interaction between Smac and IAPs involves the AVPI
      tetrapeptide binding motif on the N-terminus of Smac and a well-defined groove on
      the surface of these IAP proteins, providing an ideal site for the design of
      small-molecule Smac mimetics. Potent and cell-permeable small-molecule Smac
      mimetics have provided powerful pharmacological tools for study of the regulation
      of apoptosis by IAP proteins, and several such compounds are now in early
      clinical trials as new anticancer agents.

PMID- 21072627
TI  - The stress of starvation: glucocorticoid restraint of beta cell development.
AB  - Developmental insults during gestation, such as under-nutrition, are known to
      restrict the number of beta cells that form in the fetal pancreas and are
      maintained in adulthood, leading to increased risk of type 2 diabetes. There are
      now substantial data indicating that glucocorticoids mediate this effect of under
      nutrition on beta cell mass and that even at physiological levels they restrain
      fetal beta cell development in utero. There are emerging clues that this occurs
      downstream of endocrine commitment by neurogenin 3 but prior to terminal beta
      cell differentiation. Deciphering the precise mechanism will be important as it
      might unveil new pathways by which to manipulate beta cell mass that could be
      exploited as novel therapies for patients with diabetes.

PMID- 21072629
TI  - Survey of cyclic and linear siloxanes in sediment from the Songhua River and in
      sewage sludge from wastewater treatment plants, Northeastern China.
AB  - Siloxanes are used in a wide range of industrial applications, such as fuel
      additives, automotive polishes and waxes, and antifoaming agents, as well as in
      personal care products and biomedical devices. Despite the potential for
      environmental occurrence, few studies have reported sources and pathways of
      siloxanes in the environment. In this study, we determined concentrations of four
      cyclic siloxanes, namely, octamethylcyclotetrasiloxane (D4),
      decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6), and
      tetradecamethylcycloheptasiloxane (D7) as well as 13 linear siloxanes (L4 to
      L16), in sediments sampled from the Songhua River and in sewage sludge sampled
      from treatment plants that discharge wastewater into the Songhua River in
      northeastern China. Siloxanes were found in all of the sediment samples at total
      concentrations (sum of all cyclic and linear siloxanes) as high as 2050 ng/g dry
      weight (dw). The respective total concentration ranges for cyclic (D4, D5, D6,
      and D7) and linear (L4 to L16) siloxanes in sewage sludge were 602 to 2360 and 98
      to 3310 ng/g dw. Cyclic siloxanes were found at greater concentrations than
      linear siloxanes in sediment samples. However, the summed concentrations of
      linear siloxanes were higher than the summed concentrations of cyclic siloxanes
      in sludge samples. Among cyclic siloxanes, D7 and D5 were the dominant compounds
      in both sediment and sludge. Among linear siloxanes, L10 and L11 together
      accounted for 55% of the total concentrations in sludge samples, and L6 accounted
      for 30% of the total concentration in sediment samples. To our knowledge, this is
      the first report to document concentrations and compositions of organosiloxanes
      in sediments and sewage sludge from China.

PMID- 21072628
TI  - Targeting of the actin cytoskeleton by insecticidal toxins from Photorhabdus
      luminescens.
AB  - Photorhabdus luminescens produces several types of protein toxins, which are
      essential for participation in a trilateral symbiosis with nematodes and insects.
      The nematodes, carrying the bacteria, invade insect larvae and release the
      bacteria, which kill the insects with their toxins. Recently, the molecular
      mechanisms of the toxin complexes PTC3 and PTC5 have been elucidated. The
      biologically active components of the toxin complexes are ADP
      ribosyltransferases, which modify actin and Rho GTPases, respectively. The
      actions of the toxins are described and compared with other bacterial protein
      toxins acting on the cytoskeleton.

PMID- 21072630
TI  - Biologic responses of bacteria communities living at the mucus secretion of
      common carp (Cyprinus carpio) after exposure to the carbon nanomaterial fullerene
      (C60).
AB  - Bacteria communities living in mucus secretions of common carp Cyprinus carpio
      (Cyprinidae) were exposed to the organic nanomaterial fullerene (C(60)) to
      evaluate its potential bactericidal effects. End points analyzed were viability,
      growth, reactive oxygen species (ROS) concentration, and total antioxidant
      competence against peroxyl radicals. Viability was not affected (p > 0.05),
      whereas growth was arrested (p < 0.05) after 3 hours of exposure to the three
      concentration of C(60) assayed (0.1, 1, and 10 mg/L). Levels of RO measured at
      different C(60) concentration showed that some colonies were reactive
      (significant dose-response relation, p < 0.05) to C(60), whereas others were not.
      The nonreactive colonies to C(60) presented higher antioxidant competence to
      peroxyl radicals compared with the reactive colonies (p < 0.05). The strains
      isolated and identified by polymerase chain reaction (PCR) products of 16S rRNA
      showed a predominance of Aeromonas genus between all the isolated Gram-negative
      bacteria. Thus, the present results indicate that C(60) affects bacterial
      communities that live in mucus secretions of common carp.

PMID- 21072631
TI  - Soft tissue mass at the infrascapular fossa.

PMID- 21072634
TI  - Management of acute aortic syndrome and chronic aortic dissection.
AB  - Acute aortic syndrome (AAS) describes several life-threatening aortic
      pathologies. These include intramural hematoma, penetrating aortic ulcer, and
      acute aortic dissection (AAD). Advances in both imaging and endovascular
      treatment have led to an increase in diagnosis and improved management of these
      often catastrophic pathologies. Patients, who were previously consigned to
      medical management or high-risk open surgical repair, can now be offered
      minimally invasive solutions with reduced morbidity and mortality. Information
      from the International Registry of Acute Aortic Dissection (IRAD) database
      demonstrates how in selected patients with complicated AAD the 30-day mortality
      from open surgery is 17% and endovascular stenting is 6%. Despite these
      improvements in perioperative deaths, the risks of stroke and paraplegia remain
      with endovascular treatment (combined outcome risk 4%). The pathophysiology of
      each aspect of AAS is described. The best imaging techniques and the evolving
      role of endovascular techniques in the definitive management of AAS are discussed
      incorporating strategies to reduce perioperative morbidity.

PMID- 21072635
TI  - Pathological findings and oncological control afforded by radical prostatectomy
      in men with high-risk prostate cancer: a single-centre study.
AB  - OBJECTIVE: To assess pathological findings and oncological control afforded by
      radical prostatectomy (RP) in high-risk prostate cancers (PCa) at our
      institution. MATERIALS AND METHODS: We performed a retrospective review of
      prostate cancer patients who underwent RP between 1995 and 2006 for a high-risk
      prostate cancer (i.e., PSA >20 or biopsy Gleason >=8 or clinical stage >=T2c).
      Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml
      after surgery. Survival curves were elaborated by the Kaplan-Meier method and Cox
      proportional hazard regression analysis. For each patient, a prognostic score for
      recurrence was estimated, and a prediction model was then constructed. RESULTS:
      Overall, 138 patients were included and followed for a median time of 53 months.
      Mean age at diagnosis was 63.4 years (range 39-80) and mean pre-operative PSA was
      15.5 ng/ml (range 7.4-31). The median follow-up was 53 months (range 6-166).
      Overall, 82 patients (59%) had biochemical recurrence. The five-year PSA
      recurrence-free survival rate was 40%. In univariate analysis, clinically
      palpable tumours (T2-T3) (P = 0.032), biopsy Gleason score >=8 (P = 0.031),
      seminal vesicle invasion (pT3b), positive margins and positive lymph nodes (P <
      0.001) were significantly associated with recurrence. In multivariate analysis,
      the biopsy Gleason score >=8, seminal vesicle invasion, positive margins and
      positive lymph nodes predicted recurrence (P < 0.05). CONCLUSIONS: RP affords an
      acceptable oncological control at first-line treatment of selected patients with
      high-risk PCa. However, in certain cases, surgery alone might not be sufficient
      and may be part of a multimodal treatment including either adjuvant radiotherapy
      or androgen deprivation.

PMID- 21072664
TI  - Expression of the Wilm's tumor gene WT1 during diaphragmatic development in the
      nitrofen model for congenital diaphragmatic hernia.
AB  - PURPOSE: The nitrofen model of congenital diaphragmatic hernia (CDH) reproduces a
      typical diaphragmatic defect. However, the exact pathomechanism of CDH is still
      unknown. The Wilm's tumor 1 gene (WT1) is crucial for diaphragmatic development.
      Mutations in WT1 associated with CDH have been described in humans. Additionally,
      WT1(-/-) mice display CDH. Furthermore, WT1 is involved in the retinoid signaling
      pathway, a candidate pathway for CDH. We hypothesized that diaphragmatic WT1 gene
      expression is downregulated during diaphragmatic development in the nitrofen CDH
      model. METHODS: Pregnant rats received vehicle or nitrofen on gestational day 9
      (D9). Embryos were delivered on D13, D18 and D21. The pleuroperitoneal folds
      (PPFs) were dissected using laser capture microdissection (D13). Diaphragms of
      D18 and D21 were manually dissected. RNA was extracted and relative mRNA
      expression of WT1 was determined using real-time PCR. Immunofluorescence was
      performed to evaluate protein expression of WT1. Statistical significance was
      considered p < 0.05. RESULTS: Diaphragmatic mRNA expression of WT1 was
      significantly decreased in the nitrofen group on D13, D18 and D21. Intensity of
      immunofluorescencence of WT1 was markedly decreased in the CDH diaphragms on D13,
      D18 and D21. CONCLUSION: Downregulation of diaphragmatic WT1 gene expression may
      impair diaphragmatic development in the nitrofen CDH model.

PMID- 21072665
TI  - Determining the origin of cells in tissue engineered skin substitutes: a pilot
      study employing in situ hybridization.
AB  - BACKGROUND: Definitive and high-quality coverage of large and, in particular,
      massive skin defects remains a significant challenge in burn as well as plastic
      and reconstructive surgery because of donor site shortage. A novel and promising
      approach to overcome these problems is tissue engineering of skin. Clearly,
      before eventual clinical application, engineered skin substitutes of human origin
      must be grafted and then evaluated in animal models. For the various tests to be
      conducted it is indispensable to be able to identify human cells as such in
      culture and also to distinguish between graft and recipient tissue after
      transplantation. Here we describe a tool to identify human cells in vitro and in
      vivo. METHODS: In situ hybridization allows for the detection and localization of
      specific DNA or RNA sequences in morphologically preserved cells in culture or
      tissue sections, respectively. We used digoxigenin-labeled DNA probes
      corresponding to human-specific Alu repeats in order to identify human
      keratinocytes grown in culture together with rat cells, and also to label split
      and full thickness skin grafts of human origin after transplantation on immuno
      incompetent rats. RESULTS: Digoxigenin-labeled DNA probing resulted in an
      intensive nuclear staining of human cells, both in culture and after
      transplantation onto recipient animals, while recipient animal cells (rat cells)
      did not stain. CONCLUSION: In situ hybridization using primate-specific Alu
      probes reliably allows distinguishing between cells of human and non-human origin
      both in culture as well as in histological sections. This method is an essential
      tool for those preclinical experiments (performed on non-primate animals) that
      must be conducted before novel tissue engineered skin substitutes might be
      introduced into clinical practice.

PMID- 21072666
TI  - The GPR55 agonist lysophosphatidylinositol acts as an intracellular messenger and
      bidirectionally modulates Ca2+ -activated large-conductance K+ channels in
      endothelial cells.
AB  - Lysophospholipids are known to serve as intra- and extracellular messengers
      affecting many physiological processes. Lysophosphatidylinositol (LPI), which is
      produced in endothelial cells, acts as an endogenous agonist of the orphan
      receptor, G protein-coupled receptor 55 (GPR55). Stimulation of GPR55 by LPI
      evokes an intracellular Ca(2+) rise in several cell types including endothelial
      cells. In this study, we investigated additional direct, receptor-independent
      effects of LPI on endothelial large-conductance Ca(2+) and voltage-gated
      potassium (BK(Ca)) channels. Electrophysiological experiments in the inside-out
      configuration revealed that LPI directly affects the BK(Ca) channel gating
      properties. This effect of LPI strictly depended on the presence of Ca(2+) and
      was concentration-dependent, reversible, and dual in nature. The modulating
      effects of LPI on endothelial BK(Ca) channels correlated with their initial open
      probability (Po): stimulation at low Po (<0.3) and inhibition at high Po levels
      (>0.3). In the whole-cell configuration, LPI in the pipette facilitated membrane
      hyperpolarization in response to low (0.1-2 MUM) histamine concentrations. In
      contrast, LPI counteracted membrane hyperpolarization in response to supramaximal
      cell stimulation with histamine. These results highlight a novel receptor
      independent and direct bidirectional modulation of BK(Ca) channels by LPI on
      endothelial cells. We conclude that LPI via this mechanism serves as an important
      modulator of endothelial electrical responses to cell stimulation.

PMID- 21072667
TI  - hsf1 (+) extends chronological lifespan through Ecl1 family genes in fission
      yeast.
AB  - The heat shock factor (HSF), a protein evolutionarily conserved from yeasts to
      human, regulates the expression of a set of proteins called heat shock proteins
      (HSPs), many of which function as molecular chaperones. In Saccharomyces
      cerevisiae, the HSF binds to the 5' upstream region of YGR146C and activates its
      transcription. YGR146C encodes a functional homolog of ecl1 (+), ecl2 (+), and
      ecl3 (+) of Schizosaccharomyces pombe. At present, these Ecl1 family genes, which
      are extenders of chronological lifespan, have been identified only in fungi
      groups. Based on ChIP analysis, we identified that Hsf1 binds to the upstream DNA
      region of ecl2 (+) after heat shock in S. pombe. In Caenorhabditis elegans, heat
      shock factor HSF-1 is known to regulate aging and required for the elongation of
      longevity by dietary restriction. We found that heat shock factor Hsf1 extends
      chronological lifespan of S. pombe when overexpressed. Moreover, we show that the
      extension of chronological lifespan by the overproduction of Hsf1 mainly depends
      on ecl2 (+) among Ecl1 family genes. From these results, we suggest that HSF is a
      conserved regulator of lifespan, at least in yeast and nematode, and Ecl1 family
      genes such as YGR146C and ecl2 (+) are the direct targets of Hsf1 and mediate
      lifespan extension by Hsf1.

PMID- 21072668
TI  - Rapid excess weight loss following laparoscopic gastric bypass leads to increased
      risk of internal hernia.
AB  - BACKGROUND: Internal hernia (IH) is one of the more acute and potentially
      devastating complications after laparoscopic gastric bypass (LGB). Currently,
      there is no way to predict which patients will develop IH. We propose that
      patients who undergo periods of rapid excess weight loss (EWL) following LGB are
      more likely to develop IH. METHODS: A retrospective review of a prospectively
      collected laparoscopic gastric bypass database from our bariatric center was
      performed. Patient data between 2002 and 2009 was reviewed. Demographics, initial
      body mass index (BMI), detailed weight loss curves, and morbidity, specifically
      IH, were reviewed. Statistical analysis was performed. Logistic regression
      analysis was used to obtain an adjusted odds ratio for rapid weight loss and
      hernia development. RESULTS: We reviewed all 934 LGB procedures performed. The
      average initial BMI was 49.1 kg/m2 (range=34-91 kg/m2). EWL based on our current
      averages at 1, 3, 6, 9, and 12 months postoperatively were 20, 40, 60, 75, and
      85%. We statistically defined rapid EWL as greater than the 90th percentile for
      weight loss. Rapid EWL was noted in 33.2% (310/934) of patients. Fifty-eight
      (6.2%) patients were identified with IH. Of these, 27(46.5%) had periods of rapid
      EWL (odds ratio [OR]=1.83; 95% CI=1.07, 3.02). Bivariate analysis of patient
      factors that led to rapid EWL identified initial BMI (49.3 vs. 46.6 kg/m2) and
      rapid EWL as increasing the likelihood of developing IH (p=0.026). A multivariate
      logistic model for IH identified only rapid EWL as a predictive factor. Locations
      of IH were the jejunojejunostomy (24), Pedersen's defect (23), adhesions (9), and
      colonic mesentery (1). There were five patients with combined JJ and Pederson's
      hernias. CONCLUSION: Outcomes from missed IH can be catastrophic. In our large,
      single-center series, we have found that patients who undergo periods of rapid
      EWL are at nearly twice the risk for development of IH as the rest of the gastric
      bypass population.

PMID- 21072669
TI  - Development of an ex vivo simulated training model for laparoscopic liver
      resection.
AB  - BACKGROUND: The number of patients who have undergone laparoscopic liver surgery
      has increased in the last 15 years. It is technically challenging surgery,
      requiring both advanced laparoscopic and liver resection skills. Surgeons often
      require familiarisation with much of the equipment and techniques used in this
      type of surgery. No ex vivo model currently exists for laparoscopic liver
      resection (LLR). The aim of this study was to develop a model for acquiring the
      technical skills involved in LLR that was also able to assess and measure
      surgical performance. METHODS: The ProMIS augmented reality surgical simulator
      was selected because performance data other than time could be obtained, and the
      simulator was adapted to create the laparoscopic trainer. Twenty candidates with
      differing laparoscopic surgical experience tested the model. Three groups were
      identified, novice, intermediate, and expert, according to previous exposure to
      the laparoscopic tasks. Candidates were required to identify a tumour
      ultrasonographically, mark and transect ex vivo liver, and perform two
      laparoscopic stitches with intracorporeal knots. The ProMIS recorded the
      performance data, including instrument path lengths and time. RESULTS:
      Measurements taken from the ProMIS simulator were analysed for statistical
      differences between the groups. Expert surgeons showed a statistically
      significant difference in the time taken to identify the liver lesion and
      transect the organ. The results also demonstrate that the more difficult tasks
      such as laparoscopic suturing are completed by the expert surgeons with
      statistically significant shorter times and path lengths compared to the less
      experienced surgeons. CONCLUSION: The adapted ProMIS augmented reality simulator
      provided junior surgeons with a realistic learning environment in which to
      familiarise themselves with the equipment and techniques required for LLR. The
      model also allows assessment of the performance of individuals over time and
      within a peer group. Construct validity is proven for the suturing component of
      the model.

PMID- 21072670
TI  - Risk of recurrence after laparoscopy-assisted radical gastrectomy for gastric
      cancer performed by a single surgeon.
AB  - BACKGROUND: The risk of recurrence after laparoscopy-assisted radical gastrectomy
      (LAG) was investigated. MATERIALS AND METHODS: Clinical data of 398 consecutive
      patients who underwent radical gastrectomy with R0 resection for gastric cancer
      at Gyeongsang National University Hospital between January 2005 and December 2007
      were reviewed retrospectively. RESULTS: Of the patients, 65.4% (n = 261) and
      34.6% (n = 138) underwent LAG and open radical gastrectomy (OG), respectively. Of
      the LAG cases, 73.2% (n = 192), 10.7% (n = 28), 12.6% (n = 33), and 3.1% (n = 8)
      had stage I, II, III, and IV gastric cancer, respectively. All patients were
      followed up for a mean of 36.8 +/- 13.7 months, and 14.6% (n = 58) had recurrence
      during the follow-up period. Univariate analysis revealed that tumor size, tumor
      node-metastasis (TNM) stage, method of approach (LAG versus OG), and operation
      type were associated significantly with recurrence. Multivariate analysis
      revealed that only high TNM stage was significantly associated with recurrence (P
      = 0.00). While patients who underwent OG had higher incidence of recurrence than
      patients who underwent LAG, OG was not significantly associated with recurrence
      on multivariate analysis (P = 0.06). CONCLUSIONS: LAG and OG did not differ
      significantly in terms of recurrence, even when used in advanced gastric cancer
      cases. Multivariate analysis revealed that high TNM stage was significantly
      associated with recurrence. Thus, LAG appears to be a safe and feasible procedure
      that has the potential to be an alternative to open surgery, even for advanced
      gastric cancer.

PMID- 21072671
TI  - Objective assessment of laparoscopic suturing skills using a motion-tracking
      system.
AB  - BACKGROUND: Laparoscopic suturing skills are important for advanced laparoscopic
      surgery. However, objective assessment of these skills has not yet been
      established. The aim of this study was to assess the laparoscopic suturing skills
      of novice and experienced surgeons using an electromagnetic motion-tracking
      system. METHODS: A total of 18 surgeons, who were all right-handed, were divided
      into the following two groups according to their experience as an operator in
      laparoscopic surgery: 9 novice surgeons (fewer than 10 laparoscopic procedures)
      and 9 experienced surgeons (more than 50 laparoscopic procedures). The subjects
      performed an intracorporeal suturing task in an inanimate box laparoscopic
      trainer while the movements of their forceps were evaluated using an
      electromagnetic motion-tracking system. Their laparoscopic skills were assessed
      on the basis of the time, path length, and average speed of the forceps in each
      hand. RESULTS: Experienced surgeons completed the suturing task significantly
      faster than novice surgeons did. The left path length was significantly shorter
      for experienced surgeons than for novice surgeons, whereas the right path lengths
      did not differ. The right average speed of knot tying was significantly faster
      for experienced surgeons than for novice surgeons, whereas the left average
      speeds did not differ. CONCLUSIONS: Evaluation of psychomotor skills in
      laparoscopic suturing using an electromagnetic motion-tracking system revealed
      better results for experienced surgeons than for novice surgeons in terms of the
      time taken, left path length, and right speed of knot-tying. Furthermore,
      surgical proficiency due to experience can affect surgical dexterity of each hand
      differently. The present study also demonstrates the efficacy of this system for
      objective evaluation of laparoscopic suturing skills.

PMID- 21072673
TI  - The phase-out of the intact family in a changing world: prevention and
      intervention for every child?

PMID- 21072672
TI  - The effects of Nigella sativa against oxidative injury in a rat model of
      subarachnoid hemorrhage.
AB  - OBJECTIVE: The aim of the study was to investigate the putative neuroprotective
      effect of Nigella sativa oil (NSO) treatment against subarachnoid hemorrhage
      (SAH) in rats. METHODS: To induce SAH, rats were injected with 0.3 ml blood into
      their cisterna magna. Male Wistar albino rats were divided as control, vehicle
      treated SAH, and NSO-treated (0.2 ml/kg, intraperitoneally) SAH groups. Forty
      eight hours after SAH induction, neurological examination scores were recorded
      and the rats were decapitated. Brain tissue samples were taken for blood brain
      barrier permeability, brain water content, or determination of malondialdehyde
      (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na(+)-K(+)-ATPase
      activities. RESULTS AND DISCUSSION: On the second day of SAH induction,
      neurological examination scores were increased in SAH groups, while SAH caused
      significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, which
      were accompanied with significant increases in MDA levels and MPO activity. The
      histological observation showed vasospasm of the basillary artery. On the other
      hand, NSO treatment markedly improved the neurological scores while all oxidant
      responses were prevented, implicating that NSO treatment may be of therapeutic
      use in preventing oxidative stress due to SAH.

PMID- 21072674
TI  - Aldosterone-induced kidney injury is mediated by NFkappaB activation.
AB  - BACKGROUND: Aldosterone induces inflammation and fibrosis in the kidney, while
      nuclear factor kappaB (NFkappaB) plays key roles in inflammation mediated by
      various cytokines. Here, we determined the roles of NFkappaB activation in
      aldosterone-induced kidney injury. METHODS: We used unilaterally nephrectomized
      rats with or without continuous aldosterone infusion and 0.9% saline as drinking
      water for 3 weeks. IMD-1041, an IKKbeta inhibitor, and spironolactone were orally
      administered to inhibit NFkappaB and mineralocorticoid receptor, respectively.
      RESULTS: The aldosterone-infused rats exhibited severe kidney injury,
      hypertension, and increased expression of pro-inflammatory and fibrotic proteins,
      osteopontin, fibrinogen, collagen type I, and PAI-1. Western blotting confirmed
      NFkappaB activation by aldosterone by the increased amount of p65 in the nuclear
      fraction of the kidney, and oral IMD-1041 prevented the kidney injury and
      lessened the increase in pro-inflammatory and fibrotic proteins without
      significant changes in blood pressures. In addition, changes in angiotensin
      converting enzyme 2 (ACE2), which has been found to act as a protective factor in
      various kidney injury models, were examined. Immunofluorescence studies revealed
      the presence of ACE2 in the brush-border membrane of the proximal convoluted
      tubules and markedly blunted ACE2 staining in aldosterone-infused rats. The
      decrease in amount of ACE2 protein was confirmed by Western blotting, and IMD
      1041 also prevented the decrease in ACE2. The administration of spironolactone
      also abolished the effects of aldosterone. CONCLUSION: Our results suggest that
      aldosterone induces kidney injury via activation of NFkappaB and
      mineralocorticoid receptor, and that decreased ACE2 expression may play an
      important role in aldosterone-induced kidney injury.

PMID- 21072675
TI  - A case of reversible posterior leukoencephalopathy syndrome in a patient on
      peritoneal dialysis.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently identified
      clinical and radiologic entity. The characteristic radiologic findings are
      bilateral gray and white matter edema in the posterior regions of the cerebral
      hemispheres. The typical clinical syndrome includes headache, confusion, visual
      symptoms, and seizures. RPLS most often occurs in the setting of hypertensive
      crisis, preeclampsia, or with cytotoxic immunosuppressive therapy, but many other
      clinical settings are described, such as cryoglobulinemia, hemolytic uremic
      syndrome, systemic lupus erythematosus, and use of erythropoietin. A 24-year-old
      man, diagnosed as having anaphylactoid purpura nephritis at 12 years of age and
      who started peritoneal dialysis (PD) at 23 years of age, was admitted to our
      hospital with a seizure and consciousness disturbance. His blood pressure (BP)
      and body fluid volume had not been controlled well because of poor compliance
      with medication and PD. T2-weighted magnetic resonance imaging (MRI) revealed
      high signal intensity changes restricted to the cortex and subcortical white
      matter of the cerebellum. On the other hand, diffusion-weighted imaging showed an
      isointense signal. From these findings, he was diagnosed as having RPLS. With
      appropriate control of BP and volume control by PD and hemodialysis, his symptoms
      improved, and a follow-up cranial MRI 1 month later was almost normal. To the
      best of our knowledge, this is the first report of RPLS in an adult PD patient.

PMID- 21072676
TI  - Inflammasomes: current understanding and open questions.
AB  - The innate immune system relies on its capability to detect invading microbes,
      tissue damage, or stress via evolutionarily conserved receptors. The nucleotide
      binding domain leucine-rich repeat (NLR)-containing family of pattern recognition
      receptors includes several proteins that drive inflammation in response to a wide
      variety of molecular patterns. In particular, the NLRs that participate in the
      formation of a molecular scaffold termed the "inflammasome" have been intensively
      studied in past years. Inflammasome activation by multiple types of tissue damage
      or by pathogen-associated signatures results in the autocatalytic cleavage of
      caspase-1 and ultimately leads to the processing and thus secretion of pro
      inflammatory cytokines, most importantly interleukin (IL)-1beta and IL-18. Here,
      we review the current knowledge of mechanisms leading to the activation of
      inflammasomes. In particular, we focus on the controversial molecular mechanisms
      that regulate NLRP3 signaling and highlight recent advancements in DNA sensing by
      the inflammasome receptor AIM2.

PMID- 21072677
TI  - Biochemistry, evolution and physiological function of the Rnf complex, a novel
      ion-motive electron transport complex in prokaryotes.
AB  - Microbes have a fascinating repertoire of bioenergetic enzymes and a huge variety
      of electron transport chains to cope with very different environmental
      conditions, such as different oxygen concentrations, different electron
      acceptors, pH and salinity. However, all these electron transport chains cover
      the redox span from NADH + H(+) as the most negative donor to oxygen/H(2)O as the
      most positive acceptor or increments thereof. The redox range more negative than 
      320 mV has been largely ignored. Here, we have summarized the recent data that
      unraveled a novel ion-motive electron transport chain, the Rnf complex, that
      energetically couples the cellular ferredoxin to the pyridine nucleotide pool.
      The energetics of the complex and its biochemistry, as well as its evolution and
      cellular function in different microbes, is discussed.

PMID- 21072679
TI  - BMP-4 suppresses progesterone production by inhibiting histone H3 acetylation of
      StAR in bovine granulosa cells in vitro.
AB  - This study examined the molecular mechanism by which BMP-4 inhibits progesterone
      production and the expression of genes involved in steroidogenesis. Granulosa
      cells were cultured in medium with or without BMP-4 for 0-96 h. BMP-4 inhibited
      progesterone secretion in granulosa cells and suppressed the expression of
      steroidogenic acute regulatory protein (StAR) at the mRNA and protein levels,
      whereas BMP-4 did not affect the proliferation of granulosa cells. In addition,
      we found that BMP-4 affected the expression of SR-B1 mRNA but not LDL-R in
      granulosa cells. To examine the protein-DNA interaction at specific sites within
      the StAR gene promoter, we used the quantitative real-time PCR and the ChIP
      technique. We demonstrated that BMP-4 suppresses the acetylation of histone H3
      associated with the StAR promoter region at 48 and 72 h of culture in bovine
      granulosa cells. Our results showed for the first time that BMP-4 inhibited the
      acetylation of histone H3 associated with the StAR promoter region in bovine
      granulosa cells. Taken together, we propose that the inhibition of the
      acetylation of histone H3 associated with the StAR promoter region by BMP-4 may
      be one of the inhibitory molecular mechanisms of progesterone synthesis in
      granulosa cells. Our data suggested that theca cell-derived BMP-4 is important as
      a regulator of steroid hormone synthesis in granulosa cells during follicular
      development in the mammalian ovary.

PMID- 21072680
TI  - Over-expression of LYRM1 inhibits glucose transport in rat skeletal muscles via
      attenuated phosphorylation of PI3K (p85) and Akt.
AB  - To explore the effect of LYRM1 over-expression on basal and insulin-stimulated
      glucose uptake in rat skeletal muscle cells, and to understand the underlying
      mechanisms, Rat myoblasts (L6) transfected with either an empty expression vector
      (pcDNA3.1Myc/His B) or a LYRM1 expression vector were differentiated into
      myotubes. Glucose uptake was determined by measuring 2-deoxy-D-[(3)H] glucose
      uptake into L6 myotubes. Western blotting was performed to assess the
      translocation of insulin-sensitive glucose transporter 4 (GLUT4). It was also
      used to measure the phosphorylation and total protein contents of insulin
      signaling proteins, such as the insulin receptor (IR), insulin receptor substrate
      (IRS)-1, phosphatidylinositol-3-kinase (PI3K) p85, Akt, ERK1/2, P38, and JNK.
      LYRM1 over-expression in L6 myotubes reduced insulin-stimulated glucose uptake
      and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin
      stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine
      phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38,
      and JNK. LYRM1 regulates the function of IRS-1, PI3K, and Akt, and decreases
      GLUT4 translocation and glucose uptake in response to insulin. These observations
      highlight the potential role of LYRM1 in glucose homeostasis and possibly in the
      pathophysiology of type 2 diabetes related to obesity.

PMID- 21072681
TI  - Phenotypic and genotypic profile of human tympanic membrane derived cultured
      cells.
AB  - The human tympanic membrane (hTM), known more commonly as the eardrum, is a thin,
      multi-layered membrane that is unique in the body as it is suspended in air. When
      perforated, the hTM's primary function of sound-pressure transmission is
      compromised. For the purposes of TM reconstruction, we investigated the phenotype
      and genotype of cultured primary cells derived from hTM tissue explants, compared
      to epithelial (HaCaT cells) and mesenchymal (human dermal fibroblasts (HDF))
      reference cells. Epithelium-specific ets-1 (ESE-1), E-cadherin, keratinocyte
      growth factor-1 (KGF-1/FGF-7), keratinocyte growth factor-2 (KGF-2/FGF10),
      fibroblast growth factor receptor 1 (FGFR1), variants of fibroblast growth factor
      receptor 2 (FGFR2), fibroblast surface protein (FSP), and vimentin proteins were
      used to assess the phenotypes of all cultured cells. Wholemount and paraffin
      embedded hTM tissues were stained with ESE-1 and E-cadherin proteins to establish
      normal epithelial-specific expression patterns within the epithelial layers.
      Immunofluorescent (IF) cell staining of hTM epithelial cells (hTMk) demonstrated
      co-expression of both epithelial- and mesenchymal-specific proteins. Flow
      cytometry (FCM) analysis further demonstrated co-expression of these epithelial
      and mesenchymal-specific proteins, indicating the subcultured hTMk cells
      possessed a transitional phenotype. Gene transcript analysis of hTMk cells by
      reverse transcriptase polymerase chain reaction (RT-PCR) revealed a down
      regulation of ESE-1, E-cadherin, FGFR2, variant 1 and variant 2 (FGFR2v1 and
      FGFR2v2) between low and high passages, and up-regulation of KGF-1, KGF-2, and
      FGFR1. All results indicate a gradual shift in cell phenotype of hTMk-derived
      cells from epithelial to mesenchymal.

PMID- 21072682
TI  - Photobleaching on photonic crystal enhanced fluorescence surfaces.
AB  - The effect of resonant fluorescent enhancement from a photonic crystal surface
      upon the fluorescent photobleaching rate of Cyanine-5 labeled protein has been
      investigated. We show that the enhanced excitation mechanism for photonic crystal
      enhanced fluorescence, in which the device surface resonantly couples light from
      an excitation laser, accelerates photobleaching in proportion to the coupling
      efficiency of the laser to the photonic crystal. We also show that the enhanced
      extraction mechanism, in which the photonic crystal directs emitted photons
      approximately normal to the surface, does not play a role in the rate of
      photobleaching. We show that the photobleaching rate of dye molecules on the
      photonic crystal surface is accelerated by 30x compared to an ordinary glass
      surface, but substantial signal gain is still evident, even after extended
      periods of continuous illumination at the resonant condition.

PMID- 21072683
TI  - Interaction of potassium mono and di phosphates with bovine serum albumin studied
      by fluorescence quenching method.
AB  - The interactions between potassium mono and di phosphates and bovine serum
      albumin (BSA) were studied using fluorescence spectroscopy (FS) and ultraviolet
      spectroscopy (UV). The experimental results showed that the potassium mono and di
      phosphates could insert into the BSA and quench the inner fluorescence of BSA by
      forming the potassium mono phosphate-BSA and pottassium di phosphate-BSA
      complexes. It was found that the static quenching was the main reason leading to
      the fluorescence quenching. It was conformed by XRD and SEM techniques.

PMID- 21072684
TI  - Intracytoplasmic injection of morphologically selected spermatozoa (IMSI)
      improves outcome after assisted reproduction by deselecting physiologically poor
      quality spermatozoa.
AB  - PURPOSE: We used computer assisted sperm selection (MSOME) during cycles of
      intracytoplasmic sperm injection to test whether this technique improves results
      over traditional ICSI protocols. We also used the TUNEL assay to test whether
      MSOME could deselect physiologically abnormal spermatozoa. METHODS: Individual
      spermatozoa were examined with MSOME. Normal and abnormal spermatozoa were tested
      for the level of DNA fragmentation using TUNEL assay. In a prospective,
      randomized trial, patients were selected for standard ICSI, or IMSI techniques.
      We tested the two groups for biological and clinical parameters. RESULTS: 64.8%
      of spermatozoa, otherwise selectable for ICSI, were characterized by
      abnormalities after computer-assisted sperm analysis. These sperm were also
      characterized by an increase in the level of DNA fragmentation. We noted an
      increase in embryo quality, pregnancy and implantation rates after computerized
      sperm selection during ICSI procedures. CONCLUSIONS: Computerised selection of
      spermatozoa during ICSI procedures deselects physiological abnormal spermatozoa
      and improves clinical results.

PMID- 21072685
TI  - Molecular characterization and expression pattern of three zona pellucida 3 genes
      in the Chinese sturgeon, Acipenser sinensis.
AB  - Chinese sturgeon (Acipenser sinensis) is a rare and endangered species and also
      an important resource for the sturgeon aquaculture industry. SMART cDNAs were
      synthesized from the ovary of A. sinensis, and the full-length cDNAs of three
      zona pellucida glycoprotein 3 genes (the new gene named AsZP3) were cloned and
      sequenced. AsZP3.1, AsZP3.2, and AsZP3.3 were 1,388 base pairs (bp), 1,288, and
      1,290 bp in length, respectively, and they could be translated into proteins with
      440, 394, and 398 amino acids, respectively. High level of amino acids sequence
      identity was seen between AsZP3.2 and AsZP3.3 (about 82%), but they share low
      identity with AsZP3.1 (26 and 23%, respectively). The AsZP3.1 has 42-50% amino
      acids sequence identity values with other fish and lower values with higher
      vertebrates (38%); AsZP3.2 and AsZP3.3 shared about 30-44% sequence identity with
      higher vertebrates and other fish. RT-PCR analysis indicated that AsZP3.1
      displayed a wide tissue distribution at the mRNA levels including liver, kidney,
      spleen, heart, and ovary, but AsZP3.2 and AsZP3.3 mRNAs were expressed
      exclusively in the gonad. All three AsZP3 mRNAs were not detected during
      embryogenesis and early larval development; furthermore, they were not detected
      in the gonads of 1- and 2-year-old Chinese sturgeons. All three AsZP3 mRNAs were
      detected in the testes of 3-year-old males and in the ovaries of 4- and 5-year
      old female Chinese sturgeons.

PMID- 21072686
TI  - Role of three-dimensional rotational venography in evaluation of the left iliac
      vein in patients with chronic lower limb edema.
AB  - The aim of this study was to assess the role of three-dimensional rotational
      venography (3D RV) supplementary to two-dimensional (2D) digital subtraction
      venography (DSV) in evaluation of the left iliac vein in patients with chronic
      lower limb edema. We reviewed 34 patients with chronic lower limb edema who had
      undergone bilateral iliac 2D DSV and 3D RV of the left common iliac vein and had
      surgery in our institution. The presence, anatomical location, and size of the
      venous narrowing were assessed. Stenosis was defined as luminal narrowing of 50%
      or more compared with the prestenotic or poststenotic lumen by visual assessment.
      A measured pressure gradient of 2 mm Hg or more at surgery was considered a
      positive result. The diagnostic accuracy was higher for the 3D images (88.2%)
      than for the 2D images alone (70.6%). 3D images provided higher sensitivity (90%)
      than the 2D images alone (66.7%). The 2D images alone had excellent specificity
      (100%) and positive predictive value (100%) in the diagnosis of venous narrowing.
      2D DSV images provide specificity in diagnosis of venous stenosis of the left
      iliac vein in patients with chronic lower limb edema. In patients with negative
      2D images, additional 3D RV leads to higher diagnostic sensitivity, thereby
      providing a powerful tool for planning surgical and endovascular treatment.

PMID- 21072687
TI  - Responsiveness of the Short Musculoskeletal Function Assessment (SMFA) in
      patients with femoral neck fractures.
AB  - PURPOSE: The aim of this study was to evaluate the internal and external
      responsiveness of the Short Musculoskeletal Function Assessment (SMFA), i.e. the
      instrument's ability to capture clinically important changes, in patients with
      hip fractures within the context of a randomized controlled trial. METHODS: To
      evaluate the internal responsiveness of the SMFA, the observed change and the
      standardized response mean (SRM) in relation to the change in the Dysfunction
      Index and the Bother Index were calculated. In order to calculate external
      responsiveness, an external criterion (EC) was constructed by using the Harris
      hip score. Receiver operating characteristic (ROC) curves and logistic regression
      analysis were used in the evaluation. RESULTS: Both the Bother and the
      Dysfunction SMFA indices displayed good internal responsiveness as expressed by
      significant change scores and by moderate and large SRMs, 0.76 and 0.96,
      respectively. The ROC curve and logistic regression analyses showed that both
      indices had acceptable external responsiveness and were able to discriminate
      between patients with a less good outcome versus a moderately good or good
      outcome based on the EC while the ability to differ between patients with
      moderately good versus a good outcome was limited. The percentage of correctly
      classified cases was 64% (good/moderately good), 80% (good/less good), and 74%
      (moderately good/less good) for both the Dysfunction and Bother Indices.
      CONCLUSIONS: The SMFA had good overall responsiveness in patients with hip
      fractures and, based on our results, we conclude that the SMFA can be recommended
      for use as one of the measures to evaluate the outcome after a hip fracture.

PMID- 21072688
TI  - Prospective randomized trial of ligasure versus harmonic hemostasis technique in
      thyroidectomy.
AB  - BACKGROUND: Two surgical devices have become popular in thyroid surgery: a
      bipolar energy sealing system (B) and ultrasonic coagulation (UC). Retrospective
      and prospective studies have demonstrated that the use of these surgical devices
      for thyroidectomy compared with conventional thyroidectomy (clamp-and-tie)
      techniques reduces operative time and cost. We conducted a prospective randomized
      clinical trial to determine if there is any difference in operative time and cost
      between B and UC. MATERIALS AND METHODS: A single-blinded prospective randomized
      controlled trial was conducted at a tertiary referral center. A total of 90
      patients who required a thyroidectomy for thyroid cancer, thyroid nodules, or
      hyperthyroidism were randomized to either B or UC during thyroidectomy. The
      operative time and cost of thyroidectomy were compared between the two groups.
      RESULTS: There was no statistically significant difference in patient age,
      gender, body mass index, indication for thyroidectomy and thyroid gland weight
      between the two groups. There was no statistically significant difference in
      operating room cost or total cost for thyroidectomy between the B and UC groups.
      There was also no statistically significant difference in the operative time
      between the B and UC groups (187.6 vs. 184.2 min, P = 0.48) or in postoperative
      complication rates. The only statistically significant difference in total cost
      was between surgeons independent of the device used (P < 0.01). CONCLUSIONS: In
      thyroid surgery, total cost and operative time were similar between the two
      surgical devices used.

PMID- 21072689
TI  - Liu Shih-Hao: pioneer of translational medicine in China.
AB  - Translational medicine is a new discipline which aims to eliminate the barrier
      between preclinical and clinical medicine. Here, Dr. Li discusses the application
      of translational medicine in the research, teaching and clinical work of Prof.
      Liu Shih-Hao, the founder of endocrinology in China, who was particularly
      renowned for his early work in calcium and phosphorus metabolism. This well-known
      success story can be traced back to an early appreciation of translational
      medicine by Prof. Liu Shih-Hao, and serves as an important and revelatory lesson
      for us all.

PMID- 21072690
TI  - Contemporary single-center surgical experiences in redo procedures of the
      pancreas: improved outcome and reduction of operative risk.
AB  - INTRODUCTION: Redo procedures of the pancreas are complex operations associated
      with significant morbidity and mortality rates. The operative risk may be
      minimised when indications for redo procedure are well reflected and operation is
      performed by an experienced surgeon. The aim of this study was to confirm this
      hypothesis evaluating our experiences with redo procedures. METHODS: We reviewed
      28 patients (mean age of 54 years; range 11-75 years) undergoing a redo procedure
      of the pancreas from January 2004 to June 2008 at our hospital. The term redo
      procedure was defined as a pancreatic reoperation that was carried out after
      preceding pancreatic surgery. Relaparotomies following acute complications after
      pancreatic surgery were not taken into consideration. RESULTS: The following
      parameters were evaluated: median operative time 332 min (range 160-730 min),
      median intraoperative blood loss 625 ml (range 300-2,800 ml), median
      postoperative stay on Intensive Care Unit 20 h (range 0-112 h), median
      postoperative hospital stay 15 days (range 7-98), morbidity (14%), and mortality
      (3.6%). CONCLUSIONS: Redo procedures of the pancreas can be performed with low
      complication rates. In order to achieve a satisfactory outcome, the indication of
      redo procedures has to be well reflected, and operation may be performed by
      specialised and experienced surgeons.

PMID- 21072691
TI  - Thyroid hormones are positively associated with insulin resistance early in the
      development of type 2 diabetes.
AB  - Thyroid hormones have generally been found normal in diabetic patients. The
      question of whether variation within the euthyroid range influences insulin
      sensitivity in type 2 diabetes remains to be established. To investigate this, a
      meal was given to four groups: 17 healthy volunteers (controls), 22 first-degree
      relatives of type 2 diabetic subjects (relatives), 15 subjects with impaired
      glucose tolerance (IGT), and 24 subjects with overt type 2 diabetes (DM). Blood
      was drawn for 360 min for measurements of glucose and insulin. Plasma-free
      T4(FT4) and plasma-free-T3(FT3) levels were measured. Fasting and postprandial
      insulin resistance was assessed by HOMA-IR and ISI indices, respectively. FT4
      levels were found to be lower in controls (13.73 +/- 0.48 pmol/l) than relatives,
      IGT, and DM (15.33 +/- 0.52, 16.13 +/- 0.65, and 17.7 +/- 0.85 pmol/l,
      respectively, P = 0.007). FT3 levels were lower in controls (3.68 +/- 0.09
      pmol/l) than in relatives, IGT, and DM (4.35 +/- 0.1, 4.8 +/- 0.067, and 4.87 +/-
      0.11 pmol/l, respectively, P = 0.001). HOMA-IR was positively associated with FT4
      and FT3 levels (beta-co-efficient = 1.876 +/- 0.476, P = 0.001; and 0.406 +/-
      0.090, P = 0.001, respectively). ISI was negatively associated with FT4 and FT3
      levels (beta-co-efficient = -0.051 +/- 0.009, P = 0.001 and -0.009 +/- 0.002, P =
      0.001, respectively). In conclusion, increases of thyroid hormone levels within
      the normal range associate positively with insulin resistance. These data suggest
      that thyroid hormones may be part of the pathogenetic mechanism to explain
      metabolic derangement early in the development of type 2 diabetes.

PMID- 21072692
TI  - Greater disruption to control of voluntary saccades in autistic disorder than
      Asperger's disorder: evidence for greater cerebellar involvement in autism?
AB  - It remains unclear whether autism and Asperger's disorder (AD) exist on a symptom
      continuum or are separate disorders with discrete neurobiological underpinnings.
      In addition to impairments in communication and social cognition, motor deficits
      constitute a significant clinical feature in both disorders. It has been
      suggested that motor deficits and in particular the integrity of cerebellar
      modulation of movement may differentiate these disorders. We used a simple
      volitional saccade task to comprehensively profile the integrity of voluntary
      ocular motor behaviour in individuals with high functioning autism (HFA) or AD,
      and included measures sensitive to cerebellar dysfunction. We tested three groups
      of age-matched young males with normal intelligence (full scale, verbal, and
      performance IQ estimates >70) aged between 11 and 19 years; nine with AD, eight
      with HFA, and ten normally developing males as the comparison group. Overall, the
      metrics and dynamics of the voluntary saccades produced in this task were
      preserved in the AD group. In contrast, the HFA group demonstrated relatively
      preserved mean measures of ocular motricity with cerebellar-like deficits
      demonstrated in increased variability on measures of response time, final eye
      position, and movement dynamics. These deficits were considered to be consistent
      with reduced cerebellar online adaptation of movement. The results support the
      notion that the integrity of cerebellar modulation of movement may be different
      in AD and HFA, suggesting potentially differential neurobiological substrates may
      underpin these complex disorders.

PMID- 21072694
TI  - Algebraic and geometric understanding of cells: epigenetic inheritance of
      phenotypes between generations.
AB  - We have developed methods and systems for analyzing epigenetic information in
      cells, as well as that of genetic information, to expand our understanding of how
      living systems are determined. Because cells are minimum units reflecting
      epigenetic information, which is considered to map the history of a parallel
      processing recurrent network of biochemical reactions, their behaviors cannot be
      explained by considering only conventional DNA information-processing events. The
      role of epigenetic information in cells, which complements their genetic
      information, was inferred by comparing predictions from genetic information with
      cell behavior observed under conditions chosen to reveal adaptation processes and
      community effects. A system for analyzing epigenetic information was developed
      starting from the twin complementary viewpoints of cell regulation as an
      'algebraic' system (emphasis on temporal aspects) and as a 'geometric' system
      (emphasis on spatial aspects). The knowledge acquired from this study may lead to
      the use of cells that fully control practical applications like cell-based drug
      screening and the regeneration of organs.

PMID- 21072693
TI  - NSSR1 is regulated by testosterone in the mouse uterus and extensively expressed
      in endometrial carcinoma.
AB  - Neural salient serine/arginine-rich protein 1 (NSSR1) has been found to play
      important roles in inhibiting alternative splicing during heat shock and mitosis
      and is predominantly expressed in neural tissues such as cerebral neurons,
      cerebellar Purkinje cells and bipolar cells of the retina. Recently, NSSR1 has
      also been shown to be highly expressed in the testes, suggesting its potential
      roles in reproductive system. In this report, the expression of NSSR1 in the
      columnar epithelium of the endometrium and gland epithelium during the
      development of the mouse uterus, the regulation of NSSR1 level by testosterone in
      the adult mouse uterus, and expression level of NSSR1 in both human endometrial
      carcinomas and ovarian cancers were analyzed by quantitative real-time polymerase
      chain reaction (qRT-PCR), Western blot, and immunohistochemistry. We demonstrated
      that the expression of NSSR1 was developmentally regulated in the columnar
      epithelium of the endometrium and gland epithelium in the mouse uterus.
      Additionally, the NSSR1 level in the mouse uterus was maintained and regulated by
      testosterone. Interestingly, an enhanced level of NSSR1 was observed in both
      human endometrial carcinomas and ovarian cancers. Our results suggest that
      expression and distribution of NSSR1 is developmentally and hormonally regulated
      and up-regulated in endometrial carcinomas as well as ovarian cancers, indicating
      its potential involvement in uterine development and tumorgenesis.

PMID- 21072695
TI  - Single cell analytics: an overview.
AB  - The research field of single cell analysis is rapidly expanding, driven by
      developments in flow cytometry, microscopy, lab-on-a-chip devices, and many other
      fields. The promises of these developments include deciphering cellular
      mechanisms and the quantification of cell-to-cell differences, ideally with
      spatio-temporal resolution. However, these promises are challenging as the
      analytical techniques have to cope with minute analyte amounts and
      concentrations. We formulate first these challenges and then present state-of-the
      art analytical techniques available to investigate the different cellular
      hierarchies--from the genome to the phenome, i.e., the sum of all phenotypes.

PMID- 21072697
TI  - Chitin, chitosan and derivatives for wound healing and tissue engineering.
AB  - Naturally derived polymers possess a number of properties beneficial to wound
      healing and tissue engineering. The polysaccharides chitin and chitosan appear to
      be suitable candidates for the preparation of dressing materials and scaffolds
      for tissue regeneration due to their unique structural, physico-chemical and
      functional properties. Functionalization of these biopolymers for improvement of
      properties such as solubility or introduction of active functions and blending
      with other intrinsically bioactive polymers has attracted considerable attention
      in recent years. Such modifications would allow going beyond traditional
      approaches for treatments of dermal injuries. This chapter is a critical review
      of the advances in chitin and chitosan functionalization for wound-healing and
      tissue-engineering applications.

PMID- 21072696
TI  - Recombinamers: combining molecular complexity with diverse bioactivities for
      advanced biomedical and biotechnological applications.
AB  - The rapid development of polymer science has led to literally thousands of
      different monomers and an almost endless number of possibilities arising from
      their combination. The most promising strategy to date has been to consider
      natural products as macromolecules that provide the best option for obtaining
      functional materials. Proteins, with their high levels of complexity and
      functionality, are one of the best examples of this approach. In addition, the
      development of genetic engineering has permitted the design and highly controlled
      synthesis of proteinaceous materials with complex and advanced functionalities.
      Elastin-like recombinamers (ELRs) are presented herein as an example of an
      extraordinary convergence of different properties that is not found in any other
      synthetic polymer system. These materials are highly biocompatible, stimuli
      responsive, show unusual self-assembly properties, and can incorporate bioactive
      domains and other functionalities along the polypeptide chain. These attributes
      are an important factor in the development of biomedical and biotechnological
      applications such as tissue engineering, drug delivery, purification of
      recombinant proteins, biosensors or stimuli-responsive surfaces.

PMID- 21072698
TI  - Biology of human hair: know your hair to control it.
AB  - Hair can be engineered at different levels--its structure and surface--through
      modification of its constituent molecules, in particular proteins, but also the
      hair follicle (HF) can be genetically altered, in particular with the advent of
      siRNA-based applications. General aspects of hair biology are reviewed, as well
      as the most recent contributions to understanding hair pigmentation and the
      regulation of hair development. Focus will also be placed on the techniques
      developed specifically for delivering compounds of varying chemical nature to the
      HF, indicating methods for genetic/biochemical modulation of HF components for
      the treatment of hair diseases. Finally, hair fiber structure and chemical
      characteristics will be discussed as targets for keratin surface
      functionalization.

PMID- 21072699
TI  - Biomimetic materials for medical application through enzymatic modification.
AB  - Living organisms synthesize functional materials, based on proteins and
      polysaccharides, using enzyme-catalyzed reactions. According to the biomimetic
      approach, biomaterial matrices for tissue engineering are designed to be able to
      mimic the properties and the functions of the extracellular matrix (ECM). In this
      chapter, the most significant research efforts dedicated to the study and the
      preparation of biomimetic materials through enzymatic modifications were
      reviewed. The functionalizations of different polymeric matrices obtained through
      the catalytic activity of two enzymes (Transglutaminase, TGase and Tyrosinase,
      TYRase) were discussed. Specifically, the biomimetic applications of TGase and
      TYRase to confer appropriate biomimetic properties to the biomaterials, such as
      the possibility to obtain in situ gelling hydrogels and the incorporation of
      bioactive molecules (growth factors) and cell-binding peptides into the
      scaffolds, were reviewed.

PMID- 21072700
TI  - Measuring the mechanical properties of single microbial cells.
AB  - Many cells are considered to be susceptible to mechanical forces or "shear" in
      bioprocessing, leading to undesirable cell breakage or adverse metabolic effects.
      However, cell breakage is the aim of some processing operations, in particular
      high-pressure homogenisation and other cell disruption methods. In either case,
      the exact mechanisms of damage or disruption are obscure. One reason for this is
      that the mechanical properties of the cells are generally unknown, which makes
      investigation or prediction of the damage difficult. There are several methods
      for measuring the mechanical properties of single microbial cells, and these are
      reviewed briefly. In the context of bioprocessing research, a powerful method of
      characterising the mechanical properties of single cells is compression testing
      using micromanipulation, supplemented by mathematical modelling of the cell
      behaviour in compression. The method and associated modelling are described, with
      results mainly from studies on yeast cells. Continuing difficulties in making a
      priori predictions of cell breakage in processing are identified. In future,
      compression testing by micromanipulation might also be used in conjunction with
      other single cell analytical techniques to study mechanisms controlling form,
      growth and division of cells and their consequential mechanical behaviour. It
      ought to be possible to relate cell wall mechanics to cell wall composition and
      structure, and eventually to underlying gene expression, allowing much greater
      understanding and control of the cell mechanical properties.

PMID- 21072701
TI  - Resolution of natural microbial community dynamics by community fingerprinting,
      flow cytometry, and trend interpretation analysis.
AB  - Natural microbial communities generally have an unknown structure and composition
      because of their still not yet cultivable members. Therefore, understanding the
      relationships among the bacterial members, prediction of their behaviour, and
      controlling their functions are difficult and often only partly successful
      endeavours to date. This study aims to test a new idea that allows to follow
      community dynamics on the basis of a simple concept. Terminal restriction
      fragment length polymorphism (T-RFLP) analysis of bacterial 16S ribosomal RNA
      genes was used to describe a community profile that we define as composition of a
      community. Flow cytometry and analysis of DNA contents and forward scatter
      characteristics of the single cells were used to describe a community profile,
      which we define as structure of a community. Both approaches were brought
      together by a non-metric multidimensional scaling (n-MDS) for trend
      interpretation of changes in the complex community data sets. This was done on
      the basis of a graphical evaluation of the cytometric data, leading to the newly
      developed Dalmatian plot tool, which gave an unexpected insight into the dynamics
      of the unknown bacterial members of the investigated natural microbial community.
      The approach presented here was compared with other techniques described in the
      literature. The microbial community investigated in this study was obtained from
      a BTEX contaminated anoxic aquifer. The indigenous bacteria were allowed to
      colonise in situ microcosms consisting of activated carbon. These microcosms were
      amended with benzene and one of the electron acceptors nitrate, sulphate or
      ferric iron to stimulate microbial growth. The data obtained in this study
      indicated that the composition (via T-RFLP) and structure (via flow cytometry) of
      the natural bacterial community were influenced by the hydro-geochemical
      conditions in the test site, but also by the supplied electron acceptors, which
      led to distinct shifts in relative abundances of specific community members. It
      was concluded that engineered environments can be successfully monitored by
      single cell analytics in combination with established molecular tools and
      sophisticated statistical analyses, a combination that holds great promise for
      studying and monitoring natural microbial community behaviour.

PMID- 21072702
TI  - Light microscopic analysis of mitochondrial heterogeneity in cell populations and
      within single cells.
AB  - Heterogeneity in the shapes of individual multicellular organisms is a daily
      experience. Likewise, even a quick glance through the ocular of a light
      microscope reveals the morphological heterogeneities in genetically identical
      cultured cells, whereas heterogeneities on the level of the organelles are much
      less obvious. This short review focuses on intracellular heterogeneities at the
      example of the mitochondria and their analysis by fluorescence microscopy. The
      overall mitochondrial shape as well as mitochondrial dynamics can be studied by
      classical (fluorescence) light microscopy. However, with an organelle diameter
      generally close to the resolution limit of light, the heterogeneities within
      mitochondria cannot be resolved with conventional light microscopy. Therefore, we
      briefly discuss here the potential of subdiffraction light microscopy (nanoscopy)
      to study inner-mitochondrial heterogeneities.

PMID- 21072703
TI  - From single cells to microbial population dynamics: modelling in biotechnology
      based on measurements of individual cells.
AB  - The development of dynamic modelling of microbial populations in bioprocesses is
      reviewed. In the 1960s Arnold Fredrickson established the theoretical basis of
      such models, and other researchers have subsequently advanced them. This review
      explores the relationships that describe cell proliferation and evaluates the
      importance of the application of flow cytometry to the fundamental
      parameterisation of the models for their use in bioprocess engineering. The
      section "Individual-Based Modelling" discusses recent theoretical developments.
      Delay-differential equations are demonstrated to describe accurately temporal
      variation of the cell proliferation cycle and specialised approaches and related
      iconography are applied to stochastic and deterministic modelling of stages of
      cellular development. Synchronised cultures of the bacterium Cupriavidus necator
      were prepared and monitored using a flow cytometer. The data obtained demonstrate
      that cell proliferation could be simulated quantitatively using the developed
      model.

PMID- 21072704
TI  - Narrow-band imaging in the evaluation of villous morphology: a feasibility study
      assessing a simplified classification and observer agreement.
AB  - BACKGROUND AND STUDY AIMS: To determine the utility of narrow-band imaging with
      optical magnification (NBI-Z) in the evaluation of villous morphology. PATIENTS
      AND METHODS: Patients considered at risk of having celiac disease were invited.
      After standard endoscopy, they underwent further evaluation with NBI-Z which was
      digitally recorded. Targeted biopsies of each area videoed with NBI-Z were
      performed and tissue sent for histopathological analysis. Two expert endoscopists
      then selected the best representative videos (developmental phase). Next, 41
      representative images of these videos were classified as follows: villous
      patterns present (N) or absent (A). Images showing absence of villi were then
      classified as cerebriform (C) or flat (F), corresponding to partial or total
      villous atrophy respectively. Three NBI-Z-naive endoscopists then graded the
      videos. They underwent an interactive training session (learning phase) with
      video and images from a digital library before embarking on the actual
      assessment. To test for reproducibility, all videos were randomly reordered and
      graded again after a week. RESULTS: Forty-one videos (10 celiac disease, 31
      normal) from 21 patients (3 celiac disease, 18 normal) were analyzed. The overall
      sensitivity and specificity in correctly distinguishing the presence or absence
      of villi were 93.3% and 97.8% respectively, with interobserver and intraobserver
      agreement (kappa, kappa) at 0.82 and 0.86. The sensitivity and specificity in
      differentiating partial from total villous atrophy were 83.3% and 100%, kappa at
      0.73 and 0.68 respectively. CONCLUSIONS: Using a simplified classification, we
      demonstrated the feasibility of using NBI-Z to detect villous atrophy in patients
      presenting with suspected celiac disease.

PMID- 21072705
TI  - Comparison of transcolonic NOTES and laparoscopic peritoneoscopy for the
      detection of peritoneal metastases.
AB  - BACKGROUND AND AIMS: Peritoneoscopy by natural orifice transluminal endoscopic
      surgery (NOTES) could replace laparoscopic staging peritoneoscopy (LAP) if the
      yield were comparable to that from LAP. In previously performed porcine
      experiments, transgastric peritoneoscopy seemed inferior to LAP due to limited
      visualization of the liver. The aim of the present study was to improve liver
      visualization by using a colonic approach and to compare transcolonic
      peritoneoscopy (TCP) with the previously set LAP standard. METHODS: Small beads
      were stapled into porcine peritoneal cavities to simulate metastases. Previously
      in the same model LAP had detected 95% of beads (95% CI 87% -98%). Using a non
      inferiority design, a sample size of 33 beads was determined; these were
      distributed among six animals with randomization for numbers and location. TCP
      was performed using either standard endoscopic accessories (TCP-s) or a specially
      designed toolkit (TCP-t) in randomized order by one of two blinded endoscopists.
      Primary outcome was number of beads found and touched during peritoneoscopy.
      RESULTS: Locations of beads included abdominal peritoneum (6 beads), diaphragm
      (8), liver (18), and miscellaneous sites (1). TCP-s found 25 beads (yield 76%,
      95% CI 59% -87%). TCP-t found 19 beads (yield 58%, 95% CI 41%-71%). The majority
      of missed beads were located at the inferior liver surface: TCP-s detected 8/15
      (53%) and TCP-t 5/15 (33%) of these simulated metastases. CONCLUSIONS: In this
      prospective, experimental trial, transcolonic NOTES peritoneoscopy was inferior
      in comparison with the diagnostic laparoscopy done previously in the same model.

PMID- 21072706
TI  - Barrett's esophagus and reflux disease.

PMID- 21072707
TI  - Endoscopic diagnosis and treatment of upper gastrointestinal tumors.

PMID- 21072708
TI  - Gastrointestinal bleeding.

PMID- 21072709
TI  - Small-bowel endoscopy.

PMID- 21072711
TI  - Colon tumors and colonoscopy.

PMID- 21072712
TI  - Endoscopic ultrasonography.

PMID- 21072713
TI  - Natural orifice transluminal endoscopic surgery.

PMID- 21072714
TI  - Spiral enteroscopy: from "new kid on the block" to established deep small-bowel
      enteroscopy tool.

PMID- 21072715
TI  - Investigation and prevention of infectious outbreaks during endoscopic retrograde
      cholangiopancreatography.

PMID- 21072716
TI  - European Society of Gastrointestinal Endoscopy, European Society of
      Gastroenterology and Endoscopy Nurses and Associates, and the European Society of
      Anaesthesiology Guideline: Non-anesthesiologist administration of propofol for GI
      endoscopy.
AB  - Propofol sedation by non-anesthesiologists is an upcoming sedation regimen in
      several countries throughout Europe. Numerous studies have shown the efficacy and
      safety of this sedation regimen in gastrointestinal endoscopy. Nevertheless, this
      issue remains highly controversial. The aim of this evidence- and consensus-based
      set of guideline is to provide non-anesthesiologists with a comprehensive
      framework for propofol sedation during digestive endoscopy. This guideline
      results from a collaborative effort from representatives of the European Society
      of Gastrointestinal Endoscopy (ESGE), the European Society of Gastroenterology
      and Endoscopy Nurses and Associates (ESGENA) and the European Society of
      Anaesthesiology (ESA). These three societies have endorsed the present guideline.

PMID- 21072717
TI  - Outcomes of endoscopic papillectomy in elderly patients with ampullary adenoma or
      early carcinoma.
AB  - Outcomes for 14 elderly (age >= 70 years) patients (79.4 +/- 1.0 years) who
      underwent endoscopic papillectomy for ampullary tumors were compared with those
      of 22 younger (age < 70 years) patients (52.5 +/- 1.9 years). There were no
      differences in procedural success (100%), bleeding (5/14 vs. 6/22), adenoma
      recurrence (0/14 vs. 2/22) and median survival (24.0 vs. 25.5 months) between the
      elderly and younger patients. In younger patients, although adenoma recurrences
      (n=2) were managed endoscopically, invasive adenocarcinomas (n=3) were treated by
      pancreatoduodenectomy. All elderly patients with invasive (T2) tumors (n=5) were
      not surgically fit and underwent successful palliation with further endoscopic
      resection and stenting. Whilst all younger patients survived, five elderly
      patients died but three of these deaths were not cancer-related. Advanced age,
      therefore, did not adversely influence the outcomes of endoscopic papillectomy,
      suggesting it may be a treatment of choice for elderly patients with ampullary
      tumors or early cancer who are deemed unfit for surgery.

PMID- 21072718
TI  - Polypoid and non-pigmented small-bowel melanoma in capsule endoscopy is common.

PMID- 21072722
TI  - [Internet and citation bestsellers of the PPmP].

PMID- 21072723
TI  - [Which is the best test for my data?].

PMID- 21072724
TI  - Imaging of the peripheral nerves.

PMID- 21072725
TI  - Ultrasound and magnetic resonance imaging of the peripheral nerves: current
      techniques, promising directions, and open issues.
AB  - High-resolution ultrasound (US) and magnetic resonance (MR) imaging are the two
      imaging methods of choice for the study of peripheral nerves. The many advances
      that have been made in recent years, either by US or MR imaging, including
      diffusion tensor imaging and tractography, offer new perspectives for the
      assessment of many pathological processes affecting peripheral nerves such as
      entrapment syndromes, tumors and tumor-like lesions, and traumatic disorders.
      Most of these improvements have especially increased the spatial resolution of
      nerve imaging. US and MR imaging are complementary, each having advantages and
      disadvantages. Tractography is still emerging in the musculoskeletal field,
      particularly for the analysis of peripheral nerves, but this technique seems
      promising.

PMID- 21072726
TI  - Entrapment neuropathies I: upper limb (carpal tunnel excluded).
AB  - Several entrapment neuropathies of the upper extremity can cause hypoechoic
      swelling and nerve compression as seen at ultrasound. The ulnar nerve can be
      compressed at the cubital tunnel of the elbow and Guyon's canal at the wrist. The
      deep branch of the radial nerve can be compressed at the supinator muscle at the
      elbow, and the superficial radial nerve may be compressed at the dorsal wrist
      (Wartenberg's syndrome). In addition to compression at the carpal tunnel, the
      median nerve may be compressed at the elbow, related to a supracondylar process
      or by the pronator teres. Knowledge of these key anatomical sites of potential
      nerve compression is essential for accurate diagnosis of entrapment neuropathies.

PMID- 21072727
TI  - Entrapment neuropathies II: carpal tunnel syndrome.
AB  - Diagnostic tests in patients complaining of carpal tunnel syndrome (CTS) are
      based on physical examination, electrodiagnostic tests (EDTs), and diagnostic
      imaging. Timely diagnosis helps prevent permanent nerve damage and its sequelae
      in terms of functional impairment. Imaging provides additional information to
      that obtained from clinical tests and EDTs. By allowing direct visualization of
      the compressed median nerve (MN), ultrasound (US) and magnetic resonance imaging
      can depict the causes for secondary CTS and describe anatomical variants, such as
      a bifid MN or a persistent median artery of the forearm, as well as space
      occupying lesions including tenosynovitis and ganglion cysts. In addition,
      diagnostic imaging is of value for postoperative patients presenting with
      persistent symptoms. Finally, US is able to add information for EDT-negative
      symptomatic patients. Over time, US has increased in its sensitivity and
      specificity so it can be used as the initial test in patients presenting with
      clinical symptoms of CTS because it is now equivalent to EDT. The use of US as a
      screening test may reduce the number of EDT examinations in patients with
      suspected CTS, providing additional valuable anatomical information.

PMID- 21072728
TI  - Entrapment neuropathies III: lower limb.
AB  - Clinicians frequently encounter compressive neuropathies of the lower extremity.
      The clinical history and physical examination, along with electrodiagnostic
      testing and imaging studies, lead to the correct diagnosis. The imaging
      characteristics of the compression neuropathies can include acute and chronic
      changes in the nerves and the muscles they innervate. We provide a detailed
      review of compression neuropathies of the lower extremity with an emphasis on
      magnetic resonance (MR) imaging characteristics. We discuss the clinical
      presentation, etiology, anatomical location, and MR imaging appearance of these
      neuropathies, including the piriformis syndrome, iliacus syndrome, saphenous
      neuropathy, obturator neuropathy, lateral femoral cutaneous neuropathy (meralgia
      paresthetica), proximal tibial neuropathy, common peroneal neuropathy, deep
      peroneal neuropathy, superficial peroneal neuropathy, tarsal tunnel syndrome,
      Baxter's neuropathy, jogger's foot, sural neuropathy, and Morton's neuroma.

PMID- 21072729
TI  - Traumatic neuropathies: spectrum of imaging findings and postoperative
      assessment.
AB  - Traumatic injury to peripheral nerves is a significant cause of morbidity and
      disability. Until reinnervation occurs, electrodiagnostic studies cannot
      differentiate severe axonotmetic lesions (Sunderland class 4) from complete nerve
      transection or neurotmesis (Sunderland class 5). This limitation is relevant
      clinically because in cases of neurotmesis an improved outcome may be achieved
      with an early surgical repair (within 1 week after trauma). High-resolution
      ultrasound (US) is an efficient modality to visualize injured nerves and is
      becoming increasingly important among radiologists and surgeons. Magnetic
      resonance (MR) imaging is complementary to high-resolution US, especially in
      evaluating deep-seated and proximal nerve segments. This article describes the
      imaging features of traumatic peripheral nerve lesions. The role of diagnostic
      imaging in stretching injuries, contusion trauma, penetrating wounds, and after
      surgery is discussed. A multimodality diagnostic approach including physical
      examination, electrophysiology, and US and MR imaging allows an accurate
      evaluation of most peripheral nerves. Imaging assessment of peripheral nerves
      trauma is useful for the diagnosis, follow-up, and postoperative evaluation.

PMID- 21072731
TI  - Tumors and tumor-like lesions of peripheral nerves.
AB  - The diagnosis of a peripheral nerve tumor can often be suggested on imaging.
      Direct continuity with a neural structure or location along a typical nerve
      distribution, shape, and intrinsic magnetic resonance (MR) signal characteristics
      represent the most important signs in this regard. Although several nonneoplastic
      nerve lesions can be specifically diagnosed by MR imaging, benign and malignant
      neoplasms of peripheral nerves can usually not be distinguished with confidence.
      This article reviews the MR imaging appearance, clinical and pathological
      features of schwannoma, localized neurofibroma, plexiform neurofibroma,
      intraneural perineurioma, fibrolipomatous hamartoma, nerve sheath ganglion,
      traumatic neuroma, malignant peripheral nerve sheath tumor, and secondary
      malignant neoplasms of peripheral nerves. Typical findings are illustrated on the
      basis of histologically confirmed cases.

PMID- 21072730
TI  - Brachial plexus and nerves about the shoulder.
AB  - Ultrasound (US) and MR imaging have been shown able to detect in-depth features
      of brachial plexus anatomy and to localize pathological lesions in disorders
      where electrophysiology and physical findings are nonspecific or nonlocalizing.
      High-end gradient technology, phased array coils, and selection of an appropriate
      protocol of pulse sequences are the main requirements to evaluate the brachial
      plexus nerves with MR imaging and to distinguish between intrinsic and extrinsic
      pathological changes. A careful scanning technique based on anatomical landmarks
      is required to image the brachial plexus nerves with US. In traumatic injuries,
      MR imaging and myelographic techniques can exclude nerve lesions at the level of
      neural foramina and at intradural location. Outside the spinal canal, US is an
      excellent alternative to MR imaging to determine the presence of a lesion, to
      establish the site and the level of nerve involvement, as well as to confirm or
      exclude major nerve injuries. In addition to brachial plexus injuries, MR imaging
      and US can be contributory in a variety of nontraumatic brachial plexopathies of
      a compressive, neoplastic, and inflammatory nature. In the thoracic outlet
      syndrome, imaging performed in association with postural maneuvers can help
      diagnose dynamic compressions. MR imaging and US are also effective to recognize
      neuropathies about the shoulder girdle involving the suprascapular, axillary,
      long thoracic, and spinal accessory nerves that may mimic brachial plexopathy. In
      this article, the clinical entities just listed are discussed independently,
      providing an overview of the current status of knowledge regarding imaging
      assessment.

PMID- 21072732
TI  - Peripheral nerves: ultrasound-guided interventional procedures.
AB  - Specific ultrasound (US)-guided interventional procedures on peripheral nerves
      are reviewed in this article including regional anesthesia, biopsy of neural
      lesions, and some injection therapies. For these procedures, US is the best
      modality to provide a safe imaging guidance because of its excellent spatial
      resolution and real-time capabilities. With US guidance, the radiologist can
      visualize the needle tip continuously and ensure that the needle is placed
      precisely in the desired location, avoiding the risk of inadvertent nerve damage.
      Practical tips and tricks for US-guided needle placement, biopsy of neural
      lesions, and US-guided therapy are reviewed in this article. The use of US-guided
      injections in specific clinical settings, such as the percutaneous treatment of
      carpal tunnel syndrome, Morton's and saphenous neuromas, painful stump neuromas,
      piriformis syndrome, and meralgia paresthetica are also illustrated here. US
      allows the clinician to inject drugs with little or no patient discomfort.

PMID- 21072734
TI  - Hip velocity and arm coordination in front crawl swimming.
AB  - The hip intracyclic velocity variability and the index of coordination in front
      crawl swimming were examined in relation to performance level. 22 swimmers were
      assigned to either an elite or a recreational swimming group and performed 4 swim
      trials at different paces relative to their individual maximum velocity. A
      velocity meter system was set to determine intracyclic velocity variability and
      video analysis allowed the determination of the index of coordination. Mean
      intracyclic velocity variability was lower in the elite swimmers than the
      recreational swimmers (14.39 +/- 1.97 vs. 17.80 +/- 4.23%, p<0.05), and remained
      stable with swim pace (i. e., the relative velocity) for the elite group, whereas
      it increased for the recreational group (p<0.05). The elite swimmers were
      characterized by a lower mean index of coordination than the recreational
      swimmers (-9.6 +/- 7.1 vs. -6.9 +/- 5.0%, p<0.05), but it increased with swim
      velocity in the elite group and showed only a tendency in the recreational group
      (p=0.07). These findings suggest that low intracyclic velocity variability and
      its stability over a range of swimming paces, which result from optimized inter
      arm coordination, are characteristic of skilled performance. Thus, the
      examination of intracyclic velocity variability and index of coordination
      variability with different swim paces could provide new insight into skilled
      performance in swimming.

PMID- 21072735
TI  - Exercise training associated with diet improves heart rate recovery and cardiac
      autonomic nervous system activity in obese children.
AB  - The purpose of this study was to test the hypotheses that in obese children: 1)
      hypocaloric diet (D) improves both heart rate recovery at 1 min (Delta HRR1)
      cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in
      obese children; 2) Diet and exercise training (DET) combined leads to greater
      improvement in both Delta HRR1 after an exercise test and in CANSA, than D alone.
      Moreover, we examined the relationships among Delta HRR1, CANSA,
      cardiorespiratory fitness and anthropometric variables (AV) in obese children
      submitted to D and to DET. 33 obese children (10 +/- 0.2 years; body mass index
      (BMI) >95 (th) percentile) were divided into 2 groups: D (n=15; BMI=31 +/- 1
      kg/m2)) and DET (n=18; 29 +/- 1 kg/m2). All children performed a maximal
      cardiopulmonary exercise test on a treadmill. The Delta HRR1 or LF/HF ratio
      (P>0.05). In contrast, the DET group showed increased peak VO2 ( P=0.01) and
      improved Delta HRR1 (Delta HRR1=37.3 +/- 2.6; P=0.01) and LF/HF ratio ( P=0.001).
      The DET group demonstrated significant relationships among Delta HRR1, peak VO2
      and CANSA (P<0.05). In conclusion, DET, in contrast to D, promoted improved
      ADelta HRR1 and CANSA in obese children, suggesting a positive influence of
      increased levels of cardiorespiratory fitness by exercise training on cardiac
      autonomic activity.

PMID- 21072736
TI  - Promoting balance and strength in the middle-aged workforce.
AB  - The prevalence of sustaining fall-related injuries is high in the middle-aged
      workforce. Deficits in postural control/muscle strength represent important fall
      risk factors. The objective of this study was to examine the impact of balance
      and strength training followed by detraining on postural control and muscle
      strength in the workforce. Thirty-two adults with sedentary office work
      participated in this study and were assigned to an intervention (age 56.0 +/- 3.7
      yrs) or a control group (age 55.5 +/- 3.4 yrs). The intervention group
      participated in 8 weeks of balance and strength training conducted at the
      worksite, followed by 8 weeks of detraining. Tests included the measurement of
      (a) total centre of pressure (COP) displacements during one-legged standing, (b)
      gait velocity and stride-to-stride variability, (c) peak isometric/isokinetic
      torque and rate of torque development (RTD) of the plantar flexors, and (d)
      jumping height. After training, significant improvements in COP displacements,
      gait velocity, peak isometric/isokinetic torque, RTD, and jumping height were
      observed. During detraining, muscle strength deteriorated, whereas postural
      control improved. This fall-preventive training program conducted at the worksite
      proved to be feasible and effective. It is suggested that this training program
      should be permanently conducted to maintain/improve muscle strength.

PMID- 21072737
TI  - Leg ability factors in tennis players.
AB  - We investigated the effects of leg stiffness on running speed, jump height and
      leg power in 13 male 2(nd)- and 3(rd)-series ranked tennis players (23 +/- 3
      years old, 73.2 +/- 8.4 kg, 1.81 +/- 0.06 m). Leg stiffness and jump height were
      assessed using jumping and hopping tests. Mean running speeds over 20 m and 40 m
      (speed20 and speed40, respectively) were determined from a sprint test.
      Theoretical maximal leg power (P(maxth)) was extrapolated from a force-velocity
      test performed on a cycle ergometer. Leg stiffness averaged 478.7 +/- 181.7 N.m
      1.kg-1 (34,808 +/- 12,573 N.m-1. It was significantly correlated to speed20 and
      counter movement jump height (r=0.60, P=0.028 and r=0.58, P=0.0407,
      respectively). There were also significant correlations between P (maxth) and
      counter-movement jump height (r=0.59, P=0.0335) and between P(maxth) and speed40
      (r=0.58, P=0.0393). This study characterizes leg stiffness in tennis players and
      brings new information concerning the way it is related to several other muscular
      biomechanical parameters.

PMID- 21072738
TI  - Vibration training improves balance in unstable ankles.
AB  - Functional ankle instability (FAI) is a common condition following ankle injury
      characterised by increased risk of injury. Ankle sprains are a common acute form
      of injury suffered in dancing and loss of balance can affect not only risk of
      injury risk but also performance aesthetics. Whole body vibration training (WBVT)
      is a new rehabilitation method that has been linked with improving balance and
      muscle function. 38 female dancers with self reported unilateral FAI were
      randomly assigned in 2 groups: WBVT and control. Absolute centre of mass (COM)
      distribution during single leg stance, SEBT normalised research distances and
      Peroneus longus mean power frequency (f(med)) where measured pre and post 6-week
      intervention. There was a significant improvement in COM distribution over the 6
      weeks from 1.05 +/- 0.57 to 0.33 +/- 0.42 cm2 (P<0.05), and 4 of the 8 planes of
      direction in the SEBT Ant, Antlat, Med and Antmed from 77.5 +/- 7.1 to 84.1 +/-
      5.8% (P<0.05) compared to control groups during the course of the 6 week training
      intervention. There was no evidence of improvement in peroneus longus (f(med))
      over time (P=0.915) in either group. WBVT improved static balance and SEBT scores
      amongst dancers exhibiting ankle instability but did not affect peroneus longus
      muscle fatigue.

PMID- 21072739
TI  - Gender muscle recovery during isokinetic exercise.
AB  - The purpose of this study was to examine the effect of two between set rest
      intervals (RI) on isokinetic knee extension peak torque (PT) produced by
      sedentary women and men. Seventeen young women (27.18 +/- 4.05 yrs) and 16 young
      men (26.75 +/- 4.73 yrs) performed 3 sets of 10 unilateral isokinetic knee
      extension at 60 degrees  and 180 degrees /s. The RI between sets was 60 and 120
      s, counterbalanced across 2 testing days. Statistical evaluation of the data was
      performed using a 3-way mixed factor ANOVA (gender x rest interval x sets). Males
      and females exhibited decreases (p<0.05) in PT with 120 s RI at 60 degrees /s.
      There was no significant decline in PT in the female group during both RI at 180
      degrees /s. Men showed a significant decrease in PT only with 60 s RI. Young
      women and men require more than 120 s of RI to recover full PT at 60 degrees /s.
      However, full quadriceps's muscle strength recovery can be attained with a 60 and
      120 s at 180 degrees /s in women, but in men only with a 120 s at the same
      velocity.

PMID- 21072740
TI  - Protective effect of erythropoietin on renal injury induced by acute exhaustive
      exercise in the rat.
AB  - We investigated the protective effect of Erythropoietin (EPO) analogue rHuEPO on
      renal injury induced by acute exhaustive exercise in the rat. Rats were randomly
      allocated to one of 3 groups: normal control (C), exhaustive exercise test (ET)
      and EPO pre-treatment (rHuEPO 2 000 U/kg) plus ET (EPO+ET). Compared with
      controls, animals in the ET group had increased serum urea nitrogen, serum
      creatinine, urine protein, and renal tissue malondialdehyde (MDA) and decreased
      renal tissue nitric oxide (NO), nitric oxide synthase (NOS) and superoxide
      dismutase (SOD) activities. There was severe damage in renal tubular epithelial
      cells with a lot of cell apoptosis, and TUNEL assay revealed a remarkably high
      apoptotic index (p<0.01). Changes in renal function and kidney tissue were much
      less in the EPO+ET group (p<0.05) and the apoptotic index was much lower than in
      the ET group (18.45+/-0.32 vs. 27.55+/-0.49, p<0.05). EPO pretreatment thus
      significantly prevented renal cell apoptosis, and counteracted high MDA and low
      NO and NOS renal contents induced by exhaustive exercise. The data point to a
      potential value of EPO in preventing the acute renal injury after exhaustive
      exercise.

PMID- 21072741
TI  - Incidence of the plateau at VO 2max is dependent on the anaerobic capacity.
AB  - The purpose of this study was to address if there is an association between the
      plateau at VO (2max) and the anaerobic capacity. 9 well-trained cyclists (age
      22.2 +/- 3.5 yr, height 182.5 +/- 5.0 cm, mass 75.7 +/- 8.7 kg, VO (2max) 59.3 +/
      4.8 ml x kg(-1) x min(-1)completed both an incremental step test of 20 W x min(
      1) starting at 120 W for determination of maximal oxygen uptake (MOU) and a
      maximally accumulated oxygen deficit (MAOD) trial at 125% MOU for estimation of
      anaerobic capacity. Throughout all trials expired air was recorded on a breath-by
      breath basis. A significant inverse relationship was observed between the MAOD
      and the Delta VO (2) during the final 60 s of the MOU test (r=-0.77, p=0.008). Of
      the 9 participants it was noted that only 4 exhibited a plateau at MOU. There
      were non-significant differences for VO (2) and the associated secondary criteria
      for those exhibiting a plateau and the non-plateau responders, despite a
      significant difference for MAOD (p=0.041) between groups. These data suggest that
      incidence of the plateau at MOU is dependent on anaerobic substrate metabolism
      and that ranges of responses reported in the literature may be a consequence of
      variations in anaerobic capacity amongst participants.

PMID- 21072742
TI  - An anatomical study of the proximal hamstring muscle complex to elucidate muscle
      strains in this region.
AB  - Muscle strain injuries are common in sports, and a high incidence is reported for
      the hamstring muscles, especially in the proximal region, where the long head of
      the biceps femoris muscle is most frequently affected. To look for some
      architectural peculiarities, which would make this muscle vulnerable, 101 legs of
      embalmed human cadavers were dissected and descriptively examined, morphometric
      data were obtained in the proximal region, and slices of plastinated specimens
      were microscopically examined. The 3 muscles composing the proximal hamstring
      complex are partly twisted around each other and possess common fibrous
      adhesions. Biceps femoris (BF) and semitendinosus (ST) muscles form a common
      head, to which the ST contributes the majority of fascicles extending 9 cm down
      from the ischiac tuberosity, thereby attaching to the common tendon at a
      remarkable pennation angle. The first BF fascicles origin from the common tendon
      only at 6 cm distance from the ischiac tuberosity. It is concluded that the high
      incidence of proximal BF strains may be a misinterpretation due to insufficient
      imaging and the complex architecture. It is suggested that the pennation angle at
      which the ST inserts to the common tendon makes this muscle especially vulnerable
      for strains during forced eccentric contractions.

PMID- 21072743
TI  - Creatine activates airway epithelium in asthma.
AB  - Airway epithelium plays important roles in the pathophysiology of asthma.
      Creatine supplementation (Cr) was shown to increase asthma features in a murine
      model of allergic asthma; however, the role of the airway epithelium in this
      inflammatory response is not known. BALB/c mice were divided into control,
      creatine supplementation, ovalbumin-sensitized (OVA) and OVA plus creatine
      supplementation groups. OVA sensitization occurred on days 0, 14, 28 and 42, and
      ovalbumin challenge from days 21-53. Cr was also given on days 21-53. Total and
      differential cells counts in BALF were evaluated. Quantitative epithelial
      expression of interleukin (IL)-4, IL-5, IL-13, CCL11, CCL5, CCL2, iNOS, VCAM-1,
      ICAM-1, NF-kappaB, VEGF, TGF-beta, IGF-1, EGFR, TIMP-1, TIMP-2, MMP-9, MMP-12 and
      arginase II were performed. Cr increased the number of total cells and
      eosinophils in BALF, the epithelial content of goblet cells and the epithelial
      expression of IL-5, CCL2, iNOS, ICAM-1, NF-kappaB, TGF-beta, TIMP-1 and MMP-9
      when compared to the control group (p<0.05). Creatine supplementation also
      exacerbated goblet cell proliferation, and IL-5 and iNOS expression by epithelial
      cells compared to the OVA group (p<0.01). Creatine up-regulates the pro
      inflammatory cascade and remodelling process in this asthma model by modulating
      the expression of inflammatory mediators by epithelial cells.

PMID- 21072744
TI  - ACE and ACTN3 genotypes in older women: muscular phenotypes.
AB  - This study examined the association between ACE I/D and ACTN3 R577X polymorphisms
      and muscle-related phenotypes and their adaptation to resistance training in
      older women. Volunteers (n=246;age=66.7 +/- 5.5 years) underwent quadriceps
      strength assessment using isokinetics and fat-free mass by dual energy X-ray
      absorptiometry. 79 volunteers performed 24 weeks of resistance training and 75
      were studied as controls. Genotypes were identified by standard procedures. No
      associations were observed for muscle strength for either gene, but volunteers
      carrying the D/D genotype presented higher appendicular fat-free mass compared to
      the I-allele carriers (6.3 +/- 0.1 vs. 6.1 +/- 0.1 kg/m (2)). The X-allele
      carriers presented higher relative fat-free mass when compared to homozygous R/R
      (16.3 +/- 0.1 vs. 15.9 +/- 0.1 kg/m (2)). All fat-free mass variables were
      significantly greater for carriers of both X/X and D/D genotypes. In response to
      RT, only the I-allele carriers significantly increased fat-free mass and a
      significant training * genotype interaction was noted. These findings do not
      support a pivotal role for the studied polymorphisms in determining muscle
      strength in older women, but suggest a modest role in fat-free mass
      determination. Of note, the results provide a novel insight that these genetic
      variations may interact to determine muscle mass in older women.

PMID- 21072745
TI  - Multi-organ dysfunction in bodybuilding possibly caused by prolonged
      hypercalcemia due to multi-substance abuse: case report and review of literature.
AB  - A 26-year-old male bodybuilder was admitted to the surgical department of a
      Danish community hospital for hematemesis. During the clinical interview, he
      revealed that he had recently finished a course of anabolic steroids and
      erythropoietin. The patient also had a previous history of infections and chronic
      ulcers due to paraffin-oil injections in both upper arms one year before. Over
      the course of the next few hours, the patient developed signs of multi-organ
      dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with
      temporary anuria, and respiratory insufficiency, and was transferred to the ICU.
      After manometric monitoring on the patient's upper arms proved difficult,
      invasive blood pressure monitoring was used and revealed that the patient was in
      a state of hypertensive crisis. This case of multi-organ dysfunction was possibly
      caused by multi-substance-induced hypercalcemia.

PMID- 21072746
TI  - Blood flow of the Achilles tendon during military training.
AB  - The purpose of this study was to evaluate the vascular response of the Achilles
      tendon as indicated by power Doppler activity during a military training program
      of 6 weeks. 49 male military recruits (98 tendons) volunteered for this study.
      Before and during the military training program, the Achilles tendons were
      screened with gray-scale ultrasonography and power Doppler US. Reactive
      tendinopathies of the Achilles tendons were registered by means of a clinical
      examination, VAS-scores and VISA-A scores. The US examination, the clinical
      examination, VAS-scores and VISA-A scores showed that 13/98 tendons developed a
      reactive tendinopathy. 3 of these 13 symptomatic tendons showed intratendinous
      Doppler activity. In these tendons, pain was always present before the vascular
      response of the Achilles tendon. Both pain and hypervascularisation remained
      visible till the end of the basic military training. In 5 asymptomatic tendons
      with no structural changes of the tendon, a vascular response was seen during one
      single measurement. It can be hypothesized that there is no relationship between
      the vascular response of the Achilles tendon and the pain in a reactive
      tendinopathy. In a reactive tendinopathy, other pain mechanisms must be
      investigated in future research.

PMID- 21072747
TI  - Interval and strength training in CAD patients.
AB  - This study sought to study the effect of high intensity aerobic interval
      endurance training on peak stroke volume and maximal strength training on
      mechanical efficiency in coronary artery disease (CAD) patients. 8 CAD patients
      (age 61.4 +/- 3.7 years) trained 30 interval training sessions with 4 * 4 min
      intervals at 85-95% of peak heart rate while 10 CAD patients (age 66.5 +/- 5.5
      years) trained 24 sessions of maximal horizontal leg press. In the interval
      training group peak stroke volume increased significantly by 23% from 94.1 +/-
      23.0 mL . beat (-1) to 115.8 +/- 22.4 mL . beat (-1) (p<0.05). Peak oxygen uptake
      increased significantly by 17% from 27.2 +/- 4.5 mL . kg (-1) . min (-1) to 31.8
      +/- 5.0 mL . kg (-1) min (-1) (p<0.05) in the same group. In contrast, there was
      no such exercise training-induced change in peak stroke volume or peak oxygen
      uptake in the maximal strength training group, despite a 35% improvement in sub
      maximal walking performance.

PMID- 21072749
TI  - [Patient satisfaction with outpatient psychological services].
AB  - A validated questionnaire regarding patient satisfaction with psychological
      services is reported. There is a German and an Italian version, with a total
      sample size of 655 persons. Based on satisfaction criteria generated by the
      patients themselves, a preliminary version and consecutively the final version,
      computed according to psychometric criteria, were developed. Internal consistency
      complied with scientific requirements (Cronbach alpha=0.95 and 0.96,
      respectively). The outcome was a one-dimensional satisfaction factor, empirically
      subdivided into "relationship" and "treatment outcome". Main indication of the
      questionnaire is the demonstration of process quality. There are also preliminary
      results with respect to congruence validity.

PMID- 21072750
TI  - [Evaluation of current assessment tools in the early detection of language
      retardation in the German preventive paediatric examinations
      (Kindervorsorgeuntersuchung U7/U7A)].
AB  - OBJECTIVE: The current analysis is a contribution to user orientation and quality
      assurance that seeks to evaluate and optimise the use of German language
      development assessment tools during early paediatric toddler check-ups (
      KINDERVORSORGEUNTERSUCHUNG U7 OR U7A). METHODS: All current, standardised
      assessment tools, particularly those relevant to early detection of developmental
      language retardation - normed on German speaking children - were evaluated
      quantitatively and qualitatively with particular regard to their psychometric
      criteria (13 criteria) and design features. RESULTS: 8 assessment tools (ELAN;
      ELFRA-2; Short Form ELFRA-2; FRAKIS; FRAKIS-K; SBE-2-KT; SBE-3-KT; SETK-2) were
      located in the literature and subjected to a detailed and rigorous comparative
      analysis. Quantitatively they met 9 to 11 of the 13 psychometric criteria.
      CONCLUSION: In Germany, there are several assessment tools for dichotomous
      identification of language retardations on high levels of psychometric criteria
      that can be used in the above-mentioned preventive paediatric examinations.
      Nevertheless, the collecting of actual norm scores of representative samples
      should be kept in mind.

PMID- 21072751
TI  - [Quality of life in German nursing homes - results of a survey using the EQ-5D
      questionnaire].
AB  - In the course of reformation of the health-care system the impact of measuring
      the quality of life steadily rises. The current study reports the disease
      comprehensive quality of life of the elderly who live in nursing homes and
      compares these results with the reference value of the German population.
      Furthermore, the results from the different nursing homes are compared with one
      another in order to prove the direct influence of the nursing home itself on the
      subjective quality of life of the habitants. The survey was conducted with the
      generic questionnaire EQ-5D which is an approved index-instrument for health
      related quality of life measurement and has been translated into 102 languages so
      far. In total 342 persons from 8 different nursing homes took part in the survey,
      at least 25 persons from each nursing home. On the one hand the results show
      interesting divergences in the quality of life level between habitants and the
      German population. Differences of at least 2- up to 10-fold values have been
      proved. For example, there was a discrepancy in the fields of problems related to
      the habitant's sex, which was not documented in the study of German population.
      On the other hand high discrepancies when comparing the nursing homes among each
      other could be proved, although the age structure as well as the distribution
      between the sexes in at least 7 nursing homes was identical. So it seems that a
      direct impact of the nursing home on the quality of life of the habitants could
      be shown. The present study raises many new questions which implicate the need
      for further surveys. These findings may have a proximate effect on the future
      health-care system, which will have to involve age-based health-care provision as
      well as innovative concepts of caring.

PMID- 21072752
TI  - Molecular determination of RHD zygosity: predicting risk of hemolytic disease of
      the fetus and newborn related to anti-D.
AB  - OBJECTIVE: Development of an accurate molecular method for paternal RHD zygosity
      to predict risk to a fetus for hemolytic disease of the fetus and newborn (HDFN)
      related to anti-D. METHODS: Quantitative fluorescence polymerase chain reaction
      (QF-PCR) was used to detect RHD exons 5 and 7, using RHCE exon 7 as an internal
      control. The genotype and zygosity were determined from the peak area ratios of
      RHD exon 5 or 7 to RHCE exon 7. We tested 25 Caucasian and 25 African American
      (AA) samples whose zygosity was predicted from the Rh phenotype and an alternate
      molecular method. In addition, we tested 71 paternal samples from prenatal cases
      where fetal testing was performed. RESULTS: RHD/RHCE ratios clearly distinguished
      the RHD/D and RHD/d genotypes. RHD variants were recognized when RHD exon 5 copy
      number was discordant with exon 7. The molecular assay identified eight cases
      where the phenotype incorrectly assigned zygosity and we observed three false
      negatives in the hybrid Rhesus box assay. The prenatal results were consistent
      with the zygosity determined for the paternal samples in our study. CONCLUSIONS:
      This QF-PCR method accurately determines RHD zygosity in Caucasians and AAs and
      will help predict the risk that a fetus will inherit RHD.

PMID- 21072753
TI  - Opening the psychological black box in genetic counseling. The psychological
      impact of DNA testing is predicted by the counselees' perception, the medical
      impact by the pathogenic or uninformative BRCA1/2-result.
AB  - BACKGROUND: It has been hypothesized that the Outcomes of DNA testing (O) are
      better predicted and/or mediated by the counselees' Perception P) than by the
      actually communicated genetic Information (I). In this study, we aimed at
      quantifying the effect that perception has in genetic counseling for hereditary
      breast/ovarian cancer. METHODS: Two hundred and four women, who had previously
      been tested for BRCA1/2, participated in a retrospective questionnaire study; 93%
      had cancer. Communicated Information (I) consisted of cancer risks and BRCA1/2
      test result category: unclassified variant (n = 76), uninformative (n = 76),
      pathogenic mutation (n = 51). Four perception variables (P) were included: the
      counselees' recollections and interpretations of both the cancer risks and the
      likelihood that the cancer in their family is heritable. The Outcome variables
      (O) included life changes, counselees' medical decisions, BRCA-related self
      concept, current psychological well-being, and quality-of-life. Bootstrap
      mediation analyses determined whether relationships were direct (I->O or P->O) or
      indirect through the mediation of perception (I->P->O). RESULTS: The actually
      communicated pathogenic mutation and uninformative result directly predicted
      medical decisions (I->O), i.e. intended and performed surgery of breasts/ovaries.
      All other outcomes were only directly predicted by the counselees' perception
      (recollection and interpretation) of their cancer risks and heredity likelihood
      (P->O), or this perception mediated the outcome (I->P->O). However, this
      perception was significantly different from the actually communicated cancer
      risks (I->P). Unclassified variants were inaccurately perceived (mostly
      overestimated); this misperception predicted both psychological outcomes and
      radical medical decisions. DISCUSSION: Genetic counselors need to explicitly
      address the counselee's interpretations and intended medical decisions. In case
      of misinterpretations, additional counseling might be offered. Communication of
      unclassified variants needs special attention given the pitfall of overestimation
      of risk.

PMID- 21072754
TI  - Endoscopic CoblatorTM-assisted management of encephaloceles.
AB  - OBJECTIVES: Numerous studies have demonstrated the efficacy and safety of
      endoscopic management of cerebral spinal fluid (CSF) rhinorrhea, encephaloceles,
      and anterior skull base defects. Techniques have evolved as new instrumentation
      has developed, but typically involve meticulous bipolar cautery to decrease the
      potential for intracranial bleeding. The present study evaluated the CoblatorTM
      as a novel tool in transnasal endoscopic management of encephaloceles. STUDY
      DESIGN: Outcomes study. METHODS: A prospective cohort involving 19 patients with
      22 encephaloceles (19 spontaneous, 3 traumatic) reduced with the CoblatorTM
      (radiofrequency coblation plus bipolar modality) was compared to a retrospective
      cohort of six encephaloceles (five spontaneous, one traumatic) removed with
      endoscopic bipolar cautery. Main outcome measures included duration of
      encephalocele removal and bleeding events. Bleeding encountered during removal
      was considered a minor event unless more than one attempt at cauterization was
      required. Other data collected included standard demographics, encephalocele
      size, and complications. RESULTS: Average duration of coblation-assisted
      encephalocele removal was 15.8 minutes compared to 46 minutes with standard
      bipolar cautery (P = .0003). Average number of bleeding episodes did not
      significantly differ between groups (CoblatorTM, 1.0 +/- 1.57 vs. bipolar, 1.17
      +/- 0.98; P = .80). One episode of major bleeding occurred in the coblation group
      when an anterior ethmoid artery was encountered during removal. Encephalocele
      size was similar between groups (CoblatorTM, 17.4 mm vs. bipolar, 16.6 mm; P =
      .65). CONCLUSIONS: Radiofrequency coblation significantly increased
      intraoperative speed during encephalocele removal with similar hemostatic
      properties when compared to bipolar cautery alone and represents a useful
      instrument in the management of encephaloceles.

PMID- 21072755
TI  - Melanocytic nevi with Spitz differentiation: diagnosis and management.
AB  - OBJECTIVES: Melanocytic proliferations with Spitz differentiation present a
      difficult clinicopathologic dilemma, as their spectrum ranges from benign to
      malignant. Distinct entities include Spitz nevus, atypical Spitz nevus, and
      Spitzoid melanoma. Their histopathologic differentiation can be challenging, and
      cases of Spitzoid melanoma initially diagnosed as benign Spitz nevi are reported
      in the literature. The goal of this article is to discuss the diagnostic tools
      (including comparative genomic hybridization), which may be helpful in
      differentiating benign Spitz nevi from malignant melanoma with Spitzoid features,
      and to propose an appropriate management strategy for each entity. STUDY DESIGN:
      Retrospective case reports. METHODS: Medical records of patients referred for
      suspicious nevi were reviewed. Data regarding demographics, site, pathology
      reports, and treatment were reviewed. RESULTS: Four patients with three distinct
      diagnoses involving Spitz differentiation were identified. The pathologic
      interpretation of these biopsies was difficult and multiple dermatopathologists
      were involved. All four patients underwent excision with or without sentinel node
      biopsy. CONCLUSIONS: Otolaryngologists, plastic surgeons and dermatopathologists
      will encounter patients who have melanocytic lesions with Spitz differentiation
      at some point in their career. The management of these patients is significantly
      impacted by the histopathologic diagnosis, and should not be undertaken until it
      is confirmed, possibly with comparative genomic hybridization. In our experience,
      it is not unusual to have multiple independent pathologic examinations. We
      believe that a team approach between the surgeon and the dermatopathologist is
      crucial when diagnosing and managing patients with Spitz lesions.

PMID- 21072756
TI  - A randomized double-blind controlled trial of phosphorylcholine-coated
      tympanostomy tube versus standard tympanostomy tube in children with recurrent
      acute and chronic otitis media.
AB  - OBJECTIVE: To compare the postoperative complication rates of phosphorylcholine
      coated fluoroplastic tympanostomy tubes versus uncoated fluoroplastic
      tympanostomy tubes. METHODS: A prospective randomized double-blind controlled
      trial in children with recurrent acute otitis media and chronic otitis media with
      effusion; 240 children were randomized to receive a phosphorylcholine-coated tube
      in one ear and an uncoated tube in the other. Postoperatively, patients were
      assessed at 2 weeks and 4, 8, 12, 18, and 24 months to ascertain the incidence of
      otorrhea, tube lumen blockage, and early extrusion. RESULTS: Out of 240 children,
      5 withdrew and 16 were lost to early follow-up. The mean age was 43.8 months.
      There were no statistically significant differences in the incidence of
      postoperative otorrhea, tube blockage, and extrusion. CONCLUSIONS:
      Phosphorylcholine-coated fluoroplastic ventilation tubes do not offer any
      advantages over uncoated standard fluoroplastic tympanostomy tubes.

PMID- 21072759
TI  - Mitochondrial tyrosine phosphoproteome: new insights from an up-to-date analysis.
AB  - Tyrosine phosphorylation is a newcomer in the mitochondrial signaling and is
      currently emerging as an important mechanism for regulating mitochondrial
      processes. But to what extent? By analyzing an updated draft of the mitochondrial
      tyrosine phosphoproteome, the following observations can be drawn: more than a
      hundred mitochondrial proteins undergo tyrosine phosphorylation, phosphotyrosine
      proteins are distributed in each of the submitochondrial compartments, and
      mitochondrial tyrosine phosphorylated proteins are involved in a variety of
      functions as metabolism (electron transport chain, Krebs cycle, fatty acid and
      amino acid metabolism), solute and protein transport, mitochondrial translation
      machinery, quality protein assessment, oxidative stress, apoptosis, fission, and
      other. This large and varied collection suggests that tyrosine phosphorylation
      could be a widespread mechanism in modulating mitochondrial functions. Moreover
      the in silico model is here used to explore potential effects of tyrosine
      phosphorylation on selected mitochondrial proteins pointing out some future
      perspectives in this field.

PMID- 21072766
TI  - Secondary metabolites of plants from the genus Saussurea: chemistry and
      biological activity.
AB  - The Asteraceae family comprises ca. 1000 genera, mainly distributed in Asia and
      Europe. Saussurea DC., as the largest subgenus of this family, comprises ca. 400
      species worldwide, of which ca. 300 species occur in China. Most plants in China
      grow wild in the alpine zone of the Qingzang Plateau and adjacent regions at
      elevations of 4000 m. Plants of the genus Saussurea (Asteraceae) are used in both
      traditional Chinese folk medicine and Tibet folklore medicine, since they are
      efficacious in relieving internal heat or fever, harmonizing menstruation,
      invigorating blood circulation, stopping bleeding, alleviating pain, increasing
      energy, and curing rheumatic arthritis. A large number of biologically active
      compounds have been isolated from this genus. This review shows the chemotaxonomy
      of these compounds (215 compounds) such as sesquiterpenoids (101 compounds),
      flavonoids (19 compounds), phytosterols (15 compounds), triterpenoids (25
      compounds), lignans (32 compounds), phenolics (23 compounds), and chlorophylls
      (11 compounds). Biological activities (anti-inflammatory, anticancer, antitumor,
      hepatoprotective, anti-ulcer, cholagogic, immunosuppressive, spasmolytic,
      antimicrobial, antiparasitic, antifeedant, CNS depressant, antioxidant, etc.) of
      these compounds, including structure-activity relationships, are also discussed.

PMID- 21072767
TI  - Naturally occurring dimers from chemical perspective.

PMID- 21072768
TI  - 7,8-secolignans from Schisandra wilsoniana and their anti-HIV-1 activities.
AB  - Two new 7,8-secolignans, marphenols A and B (1 and 2, resp.), together with a
      known related derivative, 7,8-secoholostylone B (3), were isolated from the stems
      of Schisandra wilsoniana. The structures of 1 and 2 were elucidated by
      spectroscopic methods, including extensive 1D- and 2D-NMR techniques. The anti
      HIV-1 activities of 1-3 were evaluated. Compound 1 inhibited HIV-1(IIIB)-induced
      syncytia formation with an EC(50) value of 0.55 MUg ml(-1). It reduced p24
      antigen expression in acutely HIV-1(IIIB)-infected C8166 cells and primary
      isolate HIV-1(TC-2)-infected peripheral blood mononuclear cells (PBMCs), with
      EC(50) values of 3.34 and 0.52 MUg ml(-1), respectively. It showed no effects on
      the HIV-1(IIIB) replication in chronically infected H9 cells as well as fusion
      inhibition.

PMID- 21072769
TI  - New cytotoxic prostanoids from Taiwanese soft coral Clavularia viridis.
AB  - Chemical investigation of the AcOEt/MeOH extract of Clavularia viridis collected
      in Taiwan has afforded four new prostanoids, named claviridins A-D (1-4, resp.).
      The structures of compounds 1-4 were determined on the basis of 1D- and 2D-NMR
      techniques, including COSY, HMQC, HMBC, and NOESY experiments. Pharmacological
      studies revealed that compounds 1-4 exhibited potent cytotoxicity against human
      cancer cells.

PMID- 21072770
TI  - Composition and intraspecific chemical variability of the essential oil from
      Artemisia herba-alba growing wild in a Tunisian arid zone.
AB  - The intraspecific chemical variability of essential oils (50 samples) isolated
      from the aerial parts of Artemisia herba-alba Asso growing wild in the arid zone
      of Southeastern Tunisia was investigated. Analysis by GC (RI) and GC/MS allowed
      the identification of 54 essential oil components. The main compounds were beta
      thujone and alpha-thujone, followed by 1,8-cineole, camphor, chrysanthenone,
      trans-sabinyl acetate, trans-pinocarveol, and borneol. Chemometric analysis (k
      means clustering and PCA) led to the partitioning into three groups. The
      composition of two thirds of the samples was dominated by alpha-thujone or beta
      thujone. Therefore, it could be expected that wild plants of A. herba-alba
      randomly harvested in the area of Kirchaou and transplanted by local farmers for
      the cultivation in arid zones of Southern Tunisia produce an essential oil
      belonging to the alpha-thujone/beta-thujone chemotype and containing also 1,8
      cineole, camphor, and trans-sabinyl acetate at appreciable amounts.

PMID- 21072771
TI  - Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one
      derivatives structurally related with piracetam.
AB  - Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2
      oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic
      effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and
      (R,S)-3 were obtained in good yields in only two steps starting from methyl DL
      phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses
      than piracetam, used as reference drug, but it showed lower efficacy. Whereas
      diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert
      amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only
      (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds
      did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor
      coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one
      derivatives constitute a new kind of nootropic compounds.

PMID- 21072772
TI  - Synthesis of novel ligustrazine derivatives as NA+/H+ exchange inhibitors.
AB  - A novel series of 3,5,6-trimethylpyrazine-2-methoxy (or methylamino) substituted
      benzoyl-guanidine derivatives were designed and synthesized as Na(+)/H(+)
      exchange (NHE) inhibitors. In this study, compounds with electron-withdrawing
      substituents on the benzene ring seemed to improve NHE-1 inhibitory activities.
      Compounds 6d, 6k, and 6l were found to be potent inhibitors of NHE-1
      (IC(50)=3.0+/-1.6, 3.0+/-1.4, and 1.6+/-0.4 nmol/l, resp.). Furthermore, they
      showed a remarkable reduction of infarct size in the rat myocardial infarction
      model in vivo.

PMID- 21072773
TI  - Cytotoxic sesquiterpenes from Magnolia kachirachirai.
AB  - Bioassay-guided fractionation of the root wood of Magnolia kachirachirai
      (Kanehira & Yamamoto) Dandy (Magnoliaceae) led to the isolation of three new
      compounds, kachiraterpenol (1), (E)-2,3-bis(4-hydroxy-3-methoxyphenyl)prop-2-enal
      (15), and kachiranol (19), together with 27 known compounds, of which 4,4'
      dihydroxy-3,3'-dimethoxybenzophenone (16) was isolated for the first time from a
      natural source. Their structures were elucidated by spectroscopic analysis. Two
      of these isolates, costunolide (2) and dehydrosaussurea lactone (4), showed
      cytotoxic properties against MCF-7, NCI-H460, and SF-268 cancer cell lines in
      vitro.

PMID- 21072774
TI  - Antimicrobial activity of fatty acids from fruits of Peucedanum cervaria and P.
      alsaticum.
AB  - Plants of the genus Peucedanum have been used in traditional medicine for a long
      time to treat different diseases including infectious diseases. The hexane fruits
      extracts of Peucedanum cervaria and P. alsaticum were examined for antimicrobial
      activity and analyzed for their fatty acid content. Fatty acid composition of
      oils were analyzed by GC/FID in methyl ester form. Minimal inhibitory
      concentrations (MICs) of fatty acid fractions against twelve reference bacterial
      and yeast strains were performed by the twofold serial microdilution broth
      method. Fourteen fatty acids were identified. Oleic and linoleic acids were found
      to be dominant. The extracts from both plants examined exhibited inhibitory
      effects against Gram-positive strains tested with different MIC values (0.25-2
      mg/ml); however, extract from P. alsaticum possessed stronger antibacterial
      properties and a broader spectrum. The growth of Gram-negative bacteria and
      Candida spp. strains was not inhibited even at the highest extract concentration
      used (MIC>4 mg/ml). Standard fatty acids exhibited inhibitory effects towards all
      bacterial and yeast strains used in this study; however, the majority of bacteria
      were more sensitive to linoleic than to oleic acid. These results revealed, for
      the first time, that hexane extracts obtained from fruits of P. alsaticum and P.
      cervaria possess moderate in vitro antibacterial activity against Gram-positive
      bacteria including staphylococci. Linoleic and oleic acids appear to be the
      compounds responsible for this effect, and a synergistic antimicrobial effect
      between these two fatty acids was indicated.

PMID- 21072775
TI  - Chemical composition and antimicrobial activity of volatiles from Degenia
      velebitica, a European stenoendemic plant of the Brassicaceae family.
AB  - Free and glucosidic bound leaf volatiles of Degenia velebitica were isolated and
      fractionated simultaneously into H(2)O-soluble, H(2)O-insoluble, and highly
      volatile compounds by hydrodistillation-adsorption (HDA) and analyzed by GC/MS.
      Among the 24 constituents identified, the main compounds obtained by the HDA
      method were S- and/or N-atom containing compounds, i.e., 6
      (methylsulfanyl)hexanenitrile (10; 26.78%), dimethyl trisulfide (6; 26.35%),
      3,4,5-trimethylpyrazole (17; 13.33%), hex-5-enenitrile (2; 10.11%), dimethyl
      tetrasulfide (8; 4.93%), and pent-4-enyl isothiocyanate (7; 4.45%). In addition,
      O-glycosidically bound volatiles and free volatiles were isolated by solvent
      extraction. Sixteen volatile O-aglycones and twelve free volatile components were
      identified. The main O-aglycones were eugenol (19; 24.15%), 2-methoxy-4
      vinylphenol (11; 11.50%), and benzyl alcohol (20; 9.49%), and the main free
      volatiles were (9Z,12Z)-octa-9,12-dienic acid (38.35%), hexadecanoic acid
      (22.64%), and phytol (5.80%). The H(2)O-soluble volatile fraction obtained by
      HDA, containing mostly glucosinolate degradation products and 3,4,5
      trimethylpyrazole (17), was evaluated for antimicrobial activity by determining
      inhibition zones with the diffusion method as well as minimal inhibitory
      concentrations (MIC) and minimal microbicidal concentrations (MMC) with the micro
      dilution method. The fraction expressed activity against the tested Gram-positive
      and Gram-negative bacteria as well as against yeast, with MIC values equal to or
      lower than 16.7 MUg/ml.

PMID- 21072776
TI  - Induced production of halogenated diphenyl ethers from the marine-derived fungus
      Penicillium chrysogenum.
AB  - Manipulation of the fermentation of the marine-derived fungus Penicillium
      chrysogenum by addition of CaBr(2) resulted in induced production of
      bromodiphenyl ether analogs. Two new free-radical-scavenging polybrominated
      diphenyl ethers, 1 and 2, and three known diphenyl ethers, 3,3'-dihydroxy-5,5'
      dimethyldiphenyl ether (3), and an inseparable mixture of violacerol-I (4) and
      violacerol-II (5) were isolated. The structures of the two new polybromodiphenyl
      ethers 1 and 2 were assigned by combined spectroscopic-data analysis, including
      deuterium-induced isotope effect. Compounds 1-3, and a mixture of 4 and 5
      exhibited radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl
      with IC(50) values of 18, 15, 42, and 6 MUM, respectively. With the exception of
      3, the compounds were, therefore, more active than the positive control, ascorbic
      acid (IC(50) 20 MUM).

PMID- 21072777
TI  - Chemical composition, seasonal variation, and biosynthetic considerations of
      essential oils from Baccharis microdonta and B. elaeagnoides (Asteraceae).
AB  - The chemical composition and seasonal variation throughout one year of the
      essential oils from leaves of Baccharis microdonta and B. elaeagnoides, collected
      in Campos do Jordao, SP, were investigated. The composition of the latter species
      has been described for the first time. By GC (RI) and GC/MS analysis, 43
      compounds were identified, and a predominance of oxygenated sesquiterpene
      derivatives was found in both species. The main components of the B. microdonta
      oils were elemol (31; 11.7-30.6%), spathulenol (34; 4.7-9.1%), beta-caryophyllene
      (19; 3.7-6.2%), and germacrene D (24; 2.9-12.2%), and those of the B.
      elaeagnoides oils were 34 (10.1-21.5%), viridiflorol (35; 3.6-18.4%), 24 (0.9
      13.8%), and 19 (3.5-9.4%). The identified compounds were grouped according to
      their respective C-skeletons, and the percentages of occurrence of the C
      skeletons in the essential oils of leaves collected in the four seasons allowed
      identifying the preferential accumulation of different types of C-skeletons as
      well as the seasonal variation of the biosynthetic routes over the studied
      period.

PMID- 21072778
TI  - Geranium macrorrhizum L. (Geraniaceae) essential oil: a potent agent against
      Bacillus subtilis.
AB  - The volatile hydrodistilled compounds from aerial parts and rhizomes of the
      ethnopharmacologically highly valued plant species Geranium macrorrhizum L. were
      screened for their antimicrobial activity in disc-diffusion and microdilution
      assays. The assays pointed out to a very high and selective activity of the oils
      against Bacillus subtilis with minimum inhibitory concentrations (MIC) of 0.4-1.0
      MUg/ml. This prompted us to perform detailed compositional analyses of the oils.
      GC and GC/MS analyses allowed the identification of 283 constituents. The oils
      consisted mainly of sesquiterpenoids, the main ones being germacrone (49.7% in
      the oil from aerial parts) and delta-guaiene (49.2% in rhizome oil). Significant
      qualitative and quantitative compositional differences in the oils from the two
      plant parts were observed. Further antimicrobial testing enabled us to determine
      that germacrone, the major constituent of the oil from aerial parts, was not the
      sole agent responsible for the observed activity.

PMID- 21072779
TI  - Comparative larvicidal activity of essential oils from three medicinal plants
      against Aedes aegypti L.
AB  - This work aimed at comparing larvicidal activity of essential oils extracted from
      the dried leaves of Alpinia speciosa, Cymbopogon citratus, and Rosmarinus
      officinalis against Ae. aegypti larvae. The larvae were observed for 4 h and at
      24 h according to a completely randomized design with three replications and the
      following concentrations [MUl/ml]: 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, and controls
      were distilled water, and commercial standard citral, camphor, eucalyptol, alpha
      pinene, and beta-myrcene. The essential oil of C. citratus had the lowest LC50
      (0.28) and LC90 (0.56) values, followed by that of A. speciosa (0.94 and 1.2,
      resp.) and of R. officinalis (1.18 and 1.67, resp.), and only the commercial
      standards citral and alpha-pinene were larvicidal.

PMID- 21072780
TI  - Kinetics of sorption-desorption of benfuracarb insecticide in mollisols.
AB  - BACKGROUND: Sorption-desorption processes govern the movement of pesticides in
      soil. These processes determine the potential hazard of the pesticide in a given
      environment for groundwater contamination and need to be investigated. RESULTS:
      In the present study, sorption-desorption processes of benfuracarb were
      investigated using a batch method in two mollisols. The kinetics of benfuracarb
      sorption in mollisols conformed to two-compartment (1 + 1) first-order kinetics.
      The fast sorption rate constant was about 3 times higher for silt loam than for
      loam soil. However, the slow sorption rate constants were statistically similar
      for both soils. The concentration-dependent sorption-desorption isotherms of
      benfuracarb could not closely conform to the Freundlich isotherm in mollisols of
      high organic C content. The computed values of both the sorption (log K) and
      desorption (log K') capacities were higher for silt loam than for loam soil. The
      desorption index (n'/n) values in the range 30.0-41.3 indicated poor
      reversibility of sorbed benfuracarb in mollisols. CONCLUSION: In view of the
      strong sorption of benfuracarb in mollisols with only partial desorption, the
      possibility of the leaching of soil-applied benfuracarb to contaminate
      groundwaters appears to be low.

PMID- 21072784
TI  - A novel approach toward the challenge of accurately quantifying fetal DNA in
      maternal plasma.

PMID- 21072785
TI  - Periconceptional cytomegalovirus infection: pregnancy outcome and rate of
      vertical transmission.
AB  - OBJECTIVE: To evaluate pregnancy outcome and rate of vertical transmission in
      primary maternal periconceptional cytomegalovirus (CMV) infection. METHODS: All
      women serologically diagnosed with primary periconceptional CMV infection between
      1999 and 2008 were included. Periconceptional infection was defined as primary
      maternal CMV infection occurring within 4 weeks prior to the last reported
      menstrual period and up to 3 weeks following the expected date of the missed
      menstrual period. Intrauterine infection was verified by PCR and shell vial
      culture of amniotic fluid at 22-24 weeks or neonatal urine culture within 48 h of
      birth. RESULTS: Of the 59 patients studied, 43 (73%) underwent diagnostic
      amniocentesis. Eleven of the 43 patients (25.5%) were positive for CMV
      contamination. Ten of the 11 patients (90%) elected to terminate pregnancy.
      Twelve women (20.3%) declined amniocentesis: of these 2 elected to undergo a
      first-trimester termination of pregnancy and 10 gave birth to a live-born infant.
      Six of the ten neonates were negative for CMV and two tested positive for urinary
      CMV; all eight were healthy on long-term follow-up, and two were lost to follow
      up. The remaining four women had a spontaneous first-trimester abortion.
      CONCLUSION: The risk of transmission of periconceptional CMV infection is lower
      than previously reported. These data should be borne in mind when counseling
      affected couples.

PMID- 21072790
TI  - Long-range 1H-15N heteronuclear shift correlation across wide F1 spectral
      windows.
AB  - Long-range (1)H-(15)N heteronuclear shift correlation experiments at natural
      abundance are becoming more routinely utilized in the characterization of unknown
      chemical structures from a diverse range of sources including natural products
      and pharmaceuticals. Apart from the inherent challenges of the low gyromagnetic
      ratio and natural abundance of (15)N, investigators are also occasionally
      hampered by having to deal with the wide spectral range inherent to various
      nitrogen functional groups, which can exceed 500 ppm. Earlier triple resonance
      cryoprobe designs typically provided 90 degrees  (15)N pulses in the range of 35
      40 us, which did not allow the uniform excitation of wide F(1) spectral ranges
      for (1)H-(15)N GHMBC spectra. We report the results obtained with a newly
      designed Bruker 600 MHz triple resonance TCI Micro CryoProbeTM using methyl
      orange as a model compound, in which the (15)N resonances are separated by >450
      ppm.

PMID- 21072792
TI  - Two tools for applying chromatographic retention data to the mass-based
      identification of peptides during hydrogen/deuterium exchange experiments by nano
      liquid chromatography/matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Two tools are described for integrating LC elution position with mass-based data
      in hydrogen-deuterium exchange (HDX) experiments by nano-liquid
      chromatography/matrix-assisted laser desorption/ionization mass spectrometry
      (nanoLC/MALDI-MS, a novel approach to HDX-MS). The first of these, 'TOF2H-Z
      Comparator', highlights peptides in HDX experiments that are potentially
      misidentified on the basis of mass alone. The program first calculates normalized
      values for the organic solvent concentration responsible for the elution of ions
      in nanoLC/MALDI HDX experiments. It then allows the solvent gradients for the
      multiple experiments contributing to an MS/MS-confirmed peptic peptide library to
      be brought into mutual alignment by iteratively re-modeling variables among LC
      parameters such as gradient shape, solvent species, fraction duration and LC dead
      time. Finally, using the program, high-probability chromatographic outliers can
      be flagged within HDX experimental data. The role of the second tool, 'TOF2H-XIC
      Comparator', is to normalize the LC chromatograms corresponding to all
      deuteration timepoints of all HDX experiments of a project, to a common
      reference. Accurate normalization facilitates the verification of chromatographic
      consistency between all ions whose spectral segments contribute to particular
      deuterium uptake plots. Gradient normalization in this manner revealed
      chromatographic inconsistencies between ions whose masses were either
      indistinguishable or separated by precise isotopic increments.

PMID- 21072793
TI  - Determination of the natural abundance delta15N of taurine by gas chromatography
      isotope ratio measurement mass spectrometry.
AB  - The measurement of the nitrogen isotope ratio of taurine (2-aminoethanesulphonic
      acid) in biological samples has a large number of potential applications. Taurine
      is a small water-soluble molecule which is notoriously difficult to analyze due
      to its polarity and functionality. A method is described which allows the
      determination of the natural abundance delta(15)N values of taurine and
      structural analogues, such as 3-amino-1-propanesulphonic acid (APSA), by isotope
      ratio mass spectrometry interfaced to gas chromatography (GC-irm-MS). The one
      step protocol exploits the simultaneous derivatization of both functionalities of
      these aminosulphonic acids by reaction with triethylorthoacetate (TEOA).
      Conditions have been established which ensure quantitative reaction thus avoiding
      any nitrogen isotope fractionation during derivatization and workup. The
      differences in the delta(15)N values of derivatized and non-derivatized taurine
      and APSA all fall within the working range of 0.40/00 (-0.02 to 0.390/00). When
      applied to four sources of taurine with various delta(15)N values, the method
      achieved excellent reproducibility and accuracy. The optimized method enables the
      determination of the natural abundance delta(15)N values of taurine over the
      concentration range 1.5-7.84 umol.mL(-1) in samples of biological origin.

PMID- 21072794
TI  - Mass spectrometric characterization of black tea thearubigins leading to an
      oxidative cascade hypothesis for thearubigin formation.
AB  - Thearubigins are the most abundant group of phenolic pigments found in black tea,
      accounting for an estimated 60-70% of the solids in a typical black tea infusion.
      Fifty years ago the term thearubigins was first introduced and to date the
      chemical nature of the thearubigins remains largely unresolved, if not
      mysterious, despite numerous attempts made to clarify their structure.
      Thearubigins isolated from 15 commercial black teas have been analyzed using a
      strategy combining standard chemical characterization along with a series of
      modern complementary mass spectrometry techniques, including MALDI-TOF-MS, FTICR
      MS, LC/TOF-MS and LC/MS/MS. Fifteen molecular formulas have been matched to
      constituents of fresh tea leaf that have survived processing and 21 to dimeric
      transformation products such as theasinensins, theaflavins, theaflavates,
      theanaphthoquinones, theacitrins and oolongtheanins, which were further confirmed
      by ESI MS/MS. MALDI-TOF-MS data revealed an average of 5000 additional
      thearubigin components in the mass range between m/z 1000 to 2100 clearly
      defining the molecular weight range of the thearubigin fraction. Six selected
      samples have for the first time been analyzed by electrospray ionization Fourier
      transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). FT-ICR-MS data
      revealed the presence of a maximum of 9428 peaks in the mass range 300 to 1000
      m/z and molecular formulas were assigned to 1517 of them. Data interpretation
      strategies developed for petrolomics studies (van Krevelen and Kendrick analyses)
      have for the first time been applied to black tea thearubigins and a novel
      interpretation protocol has been developed to refine these procedures for the
      investigation of complex mixtures, leading to a novel hypothesis for the
      formation and structure of the black tea thearubigins named oxidative cascade
      hypothesis.

PMID- 21072795
TI  - Characterization of the volatile organic compounds of Italian 'Fossa' cheese by
      solid-phase microextraction gas chromatography/mass spectrometry.
AB  - Fossa cheese is an Italian hard cheese, ripened for up to 3 months in underground
      pits dug into tuffaceous rock. During this period, the cheese develops a unique
      flavour and intense and somewhat piquant aroma. Solid-phase microextraction gas
      chromatography/mass spectrometry (SPME-GC/MS) was utilized to characterize the
      volatile organic compounds (VOCs) of Fossa cheese. A total of 75 VOCs were
      separated and identified; in particular, the major class of compounds found in
      the cheeses ripened in the pits were the esters of fatty acids. Discriminant
      analysis of volatile profiles allowed us to distinguish between cheeses in
      different stages of seasoning (60-day-old cheese and cheese ripened an additional
      90 days in and out of the pits).

PMID- 21072796
TI  - Rapid screening and characterization of metabolites from a marine-derived
      actinomycete by high-performance liquid chromatography coupled with electrospray
      ionization quadrupole time-of-flight mass spectrometry.
AB  - A rapid and reliable method has been optimized and established for the analysis
      of the metabolites from a marine actinomycete by high-performance liquid
      chromatography coupled with electrospray ionization quadrupole time-of-flight
      mass spectrometry (HPLC/QTOF MS/MS). From MS/MS spectra, the product ions of [M +
      H](+) were recorded to provide abundant structural information of the mother
      nucleus and peptide moieties. Using the QTOF MS/MS and in-source collision
      induced dissociation (in-source CID) techniques, three main metabolites including
      actinomycin D, actinomycin V and actinomycin I were determined and characterized
      by elemental compositions of precursor and product ions (<7 ppm). Additionally,
      this method provided information about the compositions of the peptide residues
      and the sequences of the amino acid from a series of fragment ions. It proved
      useful for the identification of the metabolites in marine samples which have
      similar structures especially when there were no reference compounds available.

PMID- 21072797
TI  - Rapid monitoring of sulfur mustard degradation in solution by headspace solid
      phase microextraction sampling and gas chromatography mass spectrometry.
AB  - A method using headspace solid-phase microextraction (HS-SPME) followed by gas
      chromatography/mass spectrometry (GC/MS) analysis has been developed to gain
      insight into the degradation of the chemical warfare agent sulfur mustard in
      solution. Specifically, the described approach simplifies the sample preparation
      for GC/MS analysis to provide a rapid determination of changes in sulfur mustard
      abundance. These results were found to be consistent with those obtained using
      liquid-liquid extraction (LLE) GC/MS. The utility of the described approach was
      further demonstrated by the investigation of the degradation process in a complex
      matrix with surfactant added to assist solvation of sulfur mustard. A more rapid
      reduction in sulfur mustard abundance was observed using the HS-SPME approach
      with surfactant present and was similar to results from LLE experiments.
      Significantly, this study demonstrates that HS-SPME can simplify the sample
      preparation for GC/MS analysis to monitor changes in sulfur mustard abundance in
      solution more rapidly, and with less solvent and reagent usage than LLE.

PMID- 21072798
TI  - Folded emitters for nanoelectrospray ionization mass spectrometry.
AB  - Electrospray ionization (ESI) has revolutionized mass spectrometry (MS),
      providing a facile method for the ionization of macromolecules for analysis by
      mass. The development of nanoESI-MS has further extended the utility of ESI-MS,
      permitting the analysis of small-volume samples with enhanced sensitivity over
      conventional ESI-MS. Traditional nanoESI-MS experiments use pulled-glass
      capillary emitters, which are expensive to purchase and require specialized
      instruments and training to fabricate in-house. Furthermore, these emitters
      suffer from problems including clogging, sample contamination, and irreproducible
      spray stability. Here, we report a new emitter for nanoESI-MS, made by folding
      small pieces of polyimide tape. In comparison with conventional pulled-glass
      capillary emitters, the new emitters are inexpensive and simple to make. Their
      low cost makes them disposable after a single use, such that sample contamination
      or clogging is never a problem. Emitter performance has been evaluated for
      diverse analytes encompassing a large mass range, including small molecules,
      peptides, proteins, and synthetic polymers. In all cases, the performance is
      similar to that of pulled-glass capillary emitters, with the advantages of low
      cost, ease of use, and disposability.

PMID- 21072799
TI  - Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometric and semi-empirical calculations study of five isoflavone aglycones.
AB  - Five isoflavones, daidzein, genistein, formononetin, prunetin and biochanin A,
      known for their biological properties, are investigated by electrospray
      ionization mass spectrometry in the positive ion mode. The most probable
      protonation sites are determined taking into account semi-empirical calculations
      using the PM6 Hamiltonian. Fragmentation mechanisms are proposed based on
      accurate mass measurements, MS(3) experiments and supported by the semi-empirical
      calculations. Some of the fragmentation pathways were found to be dependent on
      the substitution pattern of the B-ring and the ions afforded by these
      fragmentations can be considered as diagnostic. It was possible to distinguish
      between prunetin and biochanin A, two isobaric isoflavone aglycones included in
      this study. Furthermore, a comparison of the fragmentation patterns of genistein
      and biochanin A, two isoflavones, with those of their flavone counterparts,
      apigenin and acacetin, enabled us to identify some key ions mainly due to
      structural features, allowing distinction to be made between these two classes of
      compounds.

PMID- 21072800
TI  - Real-time monitoring of the progress of polymerization reactions directly on
      surfaces at open atmosphere by ambient mass spectrometry.
AB  - The progress of an on-surface polymerization process involving alkyl and
      perfluoroalkyl silanes and siloxanes was monitored in real-time via easy ambient
      sonic spray ionization mass spectrometry (EASI-MS). When sprayed on surfaces, the
      organosilicon compounds present in commercially available nanofilm products
      (NFPs) react by condensation to form a polymeric coating. A NFP for coating of
      floor materials (NFP-1) and a second NFP for coating tiles and ceramics (NFP-2)
      were applied to glass, filter paper or cotton surfaces and the progress of the
      polymerization was monitored by slowly scanning the surface. Via EASI(+)-MS
      monitoring, significant changes in the composition of hydrolysates and
      condensates of 1H,1H,2H,2H-perfluorooctyl triisopropoxysilane (NFP-1) and
      hexadecyl triethoxysilane (NFP-2) were observed over time. The abundances of the
      hydrolyzed species decreased compared with those of the non-hydrolysed species
      for both NFP-1 and NFP-2 and the heavier oligomers became relatively more
      abundant over a period of 15-20 min. A similar tendency favouring the heavier
      oligomers was observed via EASI(-)-MS. This work illustrates the potential of
      ambient mass spectrometry for the direct monitoring of polymerization reactions
      on surfaces.

PMID- 21072801
TI  - In-gel protein N- and C-termini identification and its application for transgenic
      protein characterization.
AB  - A new method for the determination of N- and C-termini of a protein isolated in a
      polyacrylamide gel is introduced. In-gel partial protein hydrolysis by
      hydrochloric acid is used to generate N- and C-terminal peptides for
      identification. This new method is complementary to existing techniques. The
      application of the in-gel protein termini identification technique to the
      characterization of the transgenic protein diacylglycerol acyltransferase
      (UrDGAT2A) purified from soybean seeds is also reported here. Both N- and C
      termini of UrDGAT2A were successfully identified and the N-terminus was found to
      be blocked by acetylation. The analysis results of UrDGAT2A and two commercial
      proteins (bovine serum albumin (BSA) and alcohol dehydrogenase) are used to
      demonstrate the effectiveness of the method in identifying actual N- and C
      termini, terminal truncation and blocking.

PMID- 21072802
TI  - Seabird satellite tracking validates the use of latitudinal isoscapes to depict
      predators' foraging areas in the Southern Ocean.
AB  - Stable isotopes are increasingly being used to trace wildlife movements. A
      fundamental prerequisite of animal isotopic tracking is a good knowledge of
      spatial isotopic variations in the environment. Few accessible reference maps of
      the isotopic landscape ("isoscapes") are available for marine predators. Here, we
      validate for the first time an isotopic gradient for higher trophic levels by
      using a unique combination of a large number of satellite-tracks and subsequent
      blood plasma isotopic signatures from a wide-ranging oceanic predator. The plasma
      delta(13)C and delta(15)N values of wandering albatrosses (n = 45) were highly
      and positively correlated to the Southern Ocean latitudes at which the satellite
      tracked individuals foraged. The well-defined latitudinal baseline carbon
      isoscapes in the Southern Ocean is thus reflected in the tissue of consumers, but
      with a positive shift due to the cumulative effect of a slight (13)C-enrichment
      at each trophic level. The data allowed us to estimate the carbon isotopic
      position of the main oceanic fronts in the area, and thus to delineate robust
      isoscapes of the main foraging zones for top predators. The plasma delta(13)C and
      delta(15)N values were positively and linearly correlated, thus suggesting that
      latitudinal isoscapes also occur for delta(15)N at the base of the food web in
      oceanic waters of the Southern Ocean. The combination of device deployments with
      sampling of relevant tissues for isotopic analysis appears to be a powerful tool
      for investigating consumers' isoscapes at various spatio-temporal scales.

PMID- 21072803
TI  - Rapid and efficient glycoprotein identification through microwave-assisted
      enzymatic digestion.
AB  - Identification of protein glycosylation sites is analytically challenging due to
      the diverse glycan structures associated with a glycoprotein. Mass spectrometry
      (MS)-based identification and characterization of glycoproteins has been achieved
      predominantly with the bottom-up approach, which typically involves the enzymatic
      cleavage of proteins to peptides prior to LC/MS or LC/MS/MS analysis. However,
      the process can be challenging due to the structural variations and steric
      hindrance imposed by the attached glycans. Alternatives to conventional heating
      protocols, that increase the rate of enzymatic cleavage of glycoproteins, may aid
      in addressing these challenges. An enzymatic digestion of a glycoprotein can be
      accelerated and made more efficient through microwave-assisted digestion. In this
      paper, a systematic study was conducted to explore the efficiency of microwave
      assisted enzymatic (trypsin) digestion (MAED) of glycoproteins as compared with
      the conventional method. In addition, the optimum experimental parameters for the
      digestion such as temperature, reaction time, and microwave radiation power were
      investigated. It was determined that efficient tryptic digestion of glycoproteins
      was attained in 15 min, allowing comparable if not better sequence coverage
      through LC/MS/MS analysis. Optimum tryptic cleavage was achieved at 45 degrees C
      irrespective of the size and complexity of the glycoprotein. Moreover, MAED
      allowed the detection and identification of more peptides and subsequently higher
      sequence coverage for all model glycoprotein. MAED also did not appear to prompt
      a loss or partial cleavage of the glycan moieties attached to the peptide
      backbones.

PMID- 21072804
TI  - Multiple-stage mass spectrometry analysis of bisphenol A diglycidyl ether,
      bisphenol F diglycidyl ether and their derivatives.
AB  - The fragmentation of bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl
      ether (BFDGE) and their derivatives was studied by electrospray ionization tandem
      mass spectrometry. Multiple-stage mass spectrometry and accurate mass
      measurements were combined to establish the fragmentation pathways. BADGEs and
      BFDGEs tend to form ammonium adducts under electrospray conditions which
      fragmented easily. The fragmentation of [M+NH(4)](+) for BADGEs started with the
      cleavage of the phenyl-alkyl bond, which was followed by the alpha-cleavage of
      the ether group to generate the characteristic product ions at m/z 135,
      [C(9)H(11)O](+), and m/z 107, [C(7)H(7)O](+). The fragmentation of the BFDGE
      isomer mixtures was studied by on-line reversed-phase liquid chromatography
      coupled to multiple-stage mass spectrometry (LC/MS(n)). Information obtained from
      product ion spectra for each BFDGE isomer and its comparison with the
      fragmentation pathway of BADGE allowed each isomer and the chromatographic
      elution order to be identified.

PMID- 21072805
TI  - Olive oil or lard?: distinguishing plant oils from animal fats in the
      archeological record of the eastern Mediterranean using gas
      chromatography/combustion/isotope ratio mass spectrometry.
AB  - Distinguishing animal fats from plant oils in archaeological residues is not
      straightforward. Characteristic plant sterols, such as beta-sitosterol, are often
      missing in archaeological samples and specific biomarkers do not exist for most
      plant fats. Identification is usually based on a range of characteristics such as
      fatty acid ratios, all of which indicate that a plant oil may be present, none of
      which uniquely distinguish plant oils from other fats. Degradation and
      dissolution during burial alter fatty acid ratios and remove short-chain fatty
      acids, resulting in degraded plant oils with similar fatty acid profiles to other
      degraded fats. Compound-specific stable isotope analysis of delta(13)C(18:0) and
      delta(13)C(16:0), carried out by gas chromatography/combustion/isotope ratio mass
      spectrometry (GC/C/IRMS), has provided a means of distinguishing fish oils, dairy
      fats, ruminant and non-ruminant adipose fats, but plant oils are rarely included
      in these analyses. For modern plant oils where C(18:1) is abundant,
      delta(13)C(18:1) and delta(13)C(16:0) are usually measured. These results cannot
      be compared with archaeological data or data from other modern reference fats
      where delta(13)C(18:0) and delta(13)C(16:0) are measured, as C(18:0) and C(18:1)
      are formed by different processes resulting in different isotopic values. Eight
      samples of six modern plant oils were saponified, releasing sufficient C(18:0) to
      measure the isotopic values, which were plotted against delta(13)C(16:0). The
      isotopic values for these oils, with one exception, formed a tight cluster
      between ruminant and non-ruminant animal fats. This result complicates the
      interpretation of mixed fatty residues in geographical areas where both animal
      fats and plant oils were in use.

PMID- 21072806
TI  - A comparison of the fragmentation pathways of [Cu(II)(Ma)(Mb)]*2+ complexes where
      Ma and Mb are peptides containing either a tryptophan or a tyrosine residue.
AB  - [Cu(II)(M(a))(M(b))](*2+) complexes, where M(a) and M(b) are dipeptides or
      tripeptides each containing either a tryptophan (W) or tyrosine (Y) residue, have
      been examined by means of electrospray tandem mass spectrometry. Collision
      induced dissociations (CIDs) of complexes containing identical peptides having a
      tryptophan residue generated abundant radical cations of the peptides; by
      contrast, for complexes containing peptides having a tyrosine residue, the main
      fragmentation channel is dissociative proton transfer to give [M(a) + H](+) and
      [Cu(II)(M(b)-H)](*+). When there are two different peptides in the complex, each
      containing a tryptophan residue, radical cations are again the major products,
      with their relative abundances depending on the locations of the tryptophan
      residue in the peptides. In the CIDs of mixed complexes, where one peptide
      contains a tryptophan residue and the other a tyrosine residue, the main
      fragmentation channel is formation of the radical cation of the tryptophan
      containing peptide and not proton transfer from the tyrosine-containing peptide
      to give a protonated peptide.

PMID- 21072807
TI  - Data combination from multiple matrix-assisted laser desorption/ionization
      (MALDI) matrices: opportunities and limitations for MALDI analysis.

PMID- 21072808
TI  - Reply to the comment by Bachmaier (2010) "On the misleading use of the term
      'semivariance' in recent articles".

PMID- 21072811
TI  - Therapy and outcome of primitive neuroectodermal tumor of the jaw.
AB  - Data pertaining to outcomes in jaw primitive neuroectodermal tumor (PNET) are
      lacking. Eleven cases of jaw PNET (five maxillary and six mandibular) were
      treated at our cancer center with the same chemotherapeutic agents from June 2003
      to January 2009. Four patients underwent surgery after neoadjuvant chemotherapy
      and all received local radiotherapy. At median follow-up of 56 months (range: 19
      77 months), 7/11 patients are in sustained remission. There was no difference in
      outcome with respect to site of tumor, and whether surgery was performed or not.
      These results support the use of chemoradiation as initial modality of treatment
      rather than going for extensive and mutilating surgery.

PMID- 21072815
TI  - Insidious iron burden in pediatric patients with acute lymphoblastic leukemia.
AB  - BACKGROUND: A significant iron burden may occur after only 10 blood transfusions
      in patients with hematologic disorders. Children with acute lymphoblastic
      leukemia (ALL) routinely receive blood transfusions during therapy, although few
      studies to date have quantified transfusion-related iron burden in these
      patients. This study quantifies the transfused blood volume and resultant iron
      load in a large cohort of pediatric patients with ALL, and evaluates risk factors
      that may impact transfusion volume. METHODS: This single institution
      retrospective study evaluated 107 patients who completed therapy for ALL between
      July 1995 and March 2007. Age, weight, and hemoglobin at presentation, ALL risk
      category, leukemia cell type, and volume of blood transfusions were collected
      from medical records. RESULTS: Patients received an average of 115 ml/kg of blood
      (77 mg/kg iron) during treatment. There was a significant association between the
      volume of packed red blood cells and ALL risk category. Patients with standard
      risk disease received 90 ml/kg (60 mg/kg iron), patients with high-risk disease
      196 ml/kg (131 mg/kg iron) and patients with T-cell disease 114 ml/kg (76 mg/kg
      iron). There was no correlation between age or hemoglobin at presentation with
      amount of blood received. CONCLUSIONS: Patients with ALL often receive a
      substantial amount of iron during therapy, with patients with high-risk disease
      receiving the greatest load. As iron overload has an overlapping toxicity profile
      with chemotherapy and is treatable, screening for increased iron burden and iron
      related morbidities should be considered during long-term follow-up of patients
      with ALL, particularly in those with high-risk ALL.

PMID- 21072819
TI  - Bevacizumab and irinotecan in the treatment of children with recurrent/refractory
      medulloblastoma.
AB  - Relapsed/refractory medulloblastoma (MB) has a poor outcome regardless of the
      treatment employed. Novel therapies are needed in an effort to improve survivals.
      We present two children with recurrent/refractory MB treated with bevacizumab and
      irinotecan both given every 2 weeks. One patient also received temozolamide. The
      first patient had stable disease and remains without progression after 30 months.
      The second patient had a near complete response that was sustained for 18 months.
      The regimen was well tolerated with minimal toxicity and provided prolonged
      progression-free survival in these two patients. Prospective clinical trials are
      needed to evaluate the effectiveness of this strategy.

PMID- 21072820
TI  - Development of the Latin American Center for Pediatric Oncology Nursing
      Education.

PMID- 21072821
TI  - Molecular diagnosis and targeted therapy of a pediatric chronic eosinophilic
      leukemia patient carrying TPM3-PDGFRB fusion.
AB  - We report a rare pediatric chronic eosinophilic leukemia (CEL) case of an 8-year
      old male whose leukemic cells carried t(1; 5)(q21; q33) chromosomal abnormality.
      Sequencing analysis confirmed a TPM3-PDGFRB fusion, and the breakpoint was the
      same as adult patient. Targeted therapy with imatinib induced a rapid hematologic
      response and reduction of TPM3-PDGFRB transcripts as monitored by reverse
      transcription real-time PCR (RT-qPCR). We then established an RT-qPCR assay
      applicable to detection of all possible PDGFRB fusions and also validated this
      assay in the patient. These data should provide a valuable reference for
      management of pediatric CEL.

PMID- 21072822
TI  - Educational and vocational achievement among long-term survivors of adolescent
      cancer in Germany.
AB  - BACKGROUND: Adolescence involves graduating from school and preparing one's
      professional career. The accomplishment of these tasks may be hampered by the
      experience of cancer. This study investigates the educational and professional
      achievements of German long-term survivors of adolescent cancer. PROCEDURE: Adult
      survivors of cancer during adolescence (n = 820, age at onset between 15 and 18
      years; M = 15.8, SD = 0.9 years; age at follow-up: M = 30.4, SD = 6.0 years) were
      recruited through the German Childhood Cancer Registry. They completed self
      reports with standard items on their educational and vocational level and their
      current occupational situation. Outcomes were compared to an age-matched sample
      from the general population (German Socio-Economic Panel, n = 820, age: M = 30.4,
      SD = 6.7). Risk factors for educational and vocational underachievement were
      identified by subgroup analyses. RESULTS: Compared to peers from the general
      population, survivors of cancer during adolescence achieved higher educational
      and vocational levels. A higher proportion of survivors was employed; however,
      survivors were significantly older when starting their first occupation. Subgroup
      analyses revealed that neuropsychological late effects were associated with
      reduced rates of graduation from university and of employment among the
      survivors. No such effect of neuro-cognitive late effects occurred for high
      school graduation. CONCLUSIONS: Most German survivors of cancer during
      adolescence participate in school and vocational life without major difficulties.
      Problems particularly arise for survivors with neuropsychological sequelae.
      Further research should investigate whether these results can be attributed to
      the German support system for pediatric cancer patients or to sample effects.

PMID- 21072824
TI  - Survival by race among children with extracranial solid tumors in the United
      States between 1985 and 2005.
AB  - BACKGROUND: The National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) database was used to compare survival rates by race among children
      with common extracranial solid tumors between 1985 and 2005. PROCEDURE: Diagnosis
      and outcome data were obtained from SEER. Five-year survival probabilities were
      calculated using the Kaplan-Meier method. Survival hazard ratios were calculated
      using the Cox proportional hazards model. Survival probabilities were compared
      among Whites, Blacks, American Indians/Alaskan Natives, and Asians/Pacific
      Islanders. RESULTS: Five-year survival probabilities were higher for White
      children than for children belonging to other racial groups (77% vs. 71% for
      Blacks, 72% for American Indian/Alaskan Native, 72% for Asian/Pacific Islander).
      Male non-White children had worse 5-year survival than male White children while
      there were no differences in survival among females across racial groups. There
      was no difference when survival probabilities for Hispanic and non-Hispanic
      children were compared. Overall, Black children had a higher risk of death
      compared to White children (1.31, P < 0.05). Black children had a higher risk of
      death from germ cell tumors, hepatoblastoma and non-rhabdomyosarcoma soft tissue
      sarcomas. Asian/Pacific Islander children also had a higher risk of death overall
      (1.34, P < 0.05) and a higher risk of death from germ cell tumors, hepatocellular
      carcinoma, neuroblastoma, and Wilms tumor compared to White children.
      CONCLUSIONS: Male children from minority groups have poorer survival from
      extracranial solid malignancies than White male children. Future efforts should
      be directed at understanding the causes of these differences and at developing
      practical clinical interventions to eliminate them.

PMID- 21072829
TI  - Hematopoietic stem cell transplantation in severe congenital neutropenia.
AB  - BACKGROUND: Severe congenital neutropenia (SCN) is an immunodeficiency
      characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC)
      <0.5 * 10(9)/L. SCN is also a premalignant condition; a significant proportion of
      patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic
      hematopoietic stem cell transplantation (HSCT) is the only curative treatment for
      SCN. PROCEDURE: Since 2004, eight HSCT have been performed in seven patients at
      our center. The indications were transformation to MDS/L (n = 2), granulocyte
      colony-stimulating factor receptor (CSF3R) mutation(s) (n = 2), granulocyte
      colony-stimulating factor (G-CSF) resistance (n = 2), and at the patient's own
      request (n = 1). RESULTS: The mean age at transplantation was 13 years (2.8-28
      years) (mean follow-up 32 months, range 21-60). Three patients harbored ELANE
      mutations, three HAX1 mutations, and in one patient no causative mutation was
      identified. Two of the ELANE mutations were novel mutations. Three patients
      initially received myeloablative conditioning and four had reduced intensity
      conditioning (RIC). Three grafts were from HLA-identical siblings, three from
      matched unrelated donors and two were cord blood units. Engraftment occurred in
      all patients. Two of seven (29%) patients died; both had MDS/L and both were
      among the three that underwent myeloablative conditioning. One patient has
      chronic GVHD 2 years post-transplant. CONCLUSIONS: The role of HSCT should be
      explored further in patients with SCN. In particular, the influence of the
      conditioning regime needs to be evaluated in a larger cohort of patients.

PMID- 21072825
TI  - Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for
      patients with transfusion-dependent beta-thalassemia.
AB  - BACKGROUND: Deferasirox is an oral iron-chelating agent taken once-daily by
      patients with transfusion-dependent iron overload. However, some patients are
      unresponsive or unable to tolerate once-daily deferasirox. The current study
      evaluated whether twice-daily deferasirox treatment showed increased efficacy or
      tolerability in unresponsive or intolerant patients. PROCEDURE: Patients from two
      Taiwanese hospitals with transfusion-dependent beta-thalassemia, including those
      who showed increasing serum ferritin levels for six consecutive months, with at
      least one level >2,500 ng/dl, while treated with >30 mg/kg/day of once-daily
      deferasirox (unresponsive) or developed deferasirox-related adverse events (AEs)
      at the dosage required to maintain the iron burden balance (intolerant) and were
      treated twice-daily with the same total daily dose of deferasirox since 2008,
      were enrolled in the study and evaluated retrospectively by medical record
      review. RESULTS: Eighteen patients were included for analysis. A statistically
      significant median decrease in serum ferritin levels was detected in the 11
      unresponsive patients after 6 months of continuous twice-daily deferasirox
      treatment. Five out of the seven intolerant patients experienced either no
      deferasirox-related AEs or less severe AEs. The 12 patients from both groups (11
      unresponsive, 1 intolerant) who received continuous twice-daily deferasirox for 6
      months showed a mild but significant median increase in serum creatinine levels.
      CONCLUSIONS: Twice-daily deferasirox dosing is effective in iron chelation and
      improves tolerability in transfusion-dependent beta-thalassemia patients who are
      unresponsive to or intolerant of once-daily deferasirox. Future studies with
      greater patient numbers will be required to confirm the results reported herein.

PMID- 21072830
TI  - Genes that move the window of viability of life: lessons from bacteria thriving
      at the cold extreme: mesophiles can be turned into extremophiles by substituting
      essential genes.
AB  - Whether occurrence of life at the physicochemical extremes results from the
      entire adaptation of organisms to such settings or it originates from the action
      of a few genes has been debated for a long time. Recent evidence suggests that a
      limited number of functions suffice to change the predilection of microorganisms
      for radically different environmental scenarios. For instance, expression of a
      few genes from cold-loving bacteria in mesophilic hosts allows them to grow at
      much lower temperatures and become heat-sensitive. This has been exploited not
      only for constructing Escherichia coli strains able to grow at 5-10  degrees C
      (and thus optimised as hosts for heterologous gene expression) but also for
      designing vaccines based on temperature-sensitive pathogens. Occurrence of
      genes/functions that reframe the windows of viability may also ask for a revision
      of some concepts in microbial ecology and may provide new tools for engineering
      bacteria with a superior biotechnological performance.

PMID- 21072832
TI  - Prevalence of advanced bone age in a cohort of patients who received cis-retinoic
      acid for high-risk neuroblastoma.
AB  - In the last decade, 13-cis-retinoic acid (13-cis-RA) has been added to the
      treatment of patients with high-risk neuroblastoma. In survivors of
      neuroblastoma, short stature is consistently observed. Causes include growth
      hormone deficiency and poor growth of irradiated long bones. Within the
      survivorship program at CHOP, we have observed that a number of these patients
      also have advanced bone ages. Children treated with 13-cis-RA are at risk for
      advanced bone age that may dramatically impact their linear growth. Ongoing
      evaluation is necessary to examine the effect of 13-cis-RA on final adult height
      and to inform clinical practice in this cohort.

PMID- 21072835
TI  - Endoscopic ultrasound-guided paracentesis of ascitic fluid: a morphologic study
      with ultrasonographic correlation.
AB  - BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has
      been widely used for the diagnosis of primary and metastatic gastrointestinal
      (GI) and non-GI malignancies. Few studies have been published to evaluate the
      accuracy and the cytologic features of EUS-guided paracentesis in the diagnosis
      and staging of malignant neoplasms. METHODS: All EUS-guided paracenteses of
      ascitic fluid performed at the University of California Irvine Medical Center
      (UCIMC) from January 2003 to February 2006 were retrospectively retrieved.
      Corresponding EUS findings, cytology and histology slides, and follow-up
      information were reviewed. RESULTS: One hundred one (101) cases were found. Two
      smears were submitted in 11 cases because of the scanty amount of fluid
      aspirated. In the remaining cases, 5 mL or less of fluid were aspirated in 56
      patients, and, of 9 who had prior computed tomography (CT), ascitic fluid was not
      seen in 6. The cytologic diagnoses were as follows: 17 were positive for
      adenocarcinoma, 1 positive for metastatic small-cell carcinoma of the lung, 1
      positive for diffuse large-cell lymphoma, 3 suspicious for adenocarcinoma, 1
      suspicious for plasmacytoma, 4 atypical epithelial cells, and 74 negative. Cell
      block was available in 80 cases and immunohistochemical stains were performed in
      71 cases to confirm the diagnosis. Six patients had peritoneal biopsy. The
      sensitivity, specificity, positive and negative predictive values, and diagnostic
      accuracy were 80%, 100%, 100%, 95%, and 96%, respectively. CONCLUSIONS: EUS
      guided paracentesis is a valuable aid in the cytologic diagnosis of malignant
      ascites. It is particularly useful when no abnormality is identified by CT.

PMID- 21072838
TI  - Metal removal efficiency and ecotoxicological assessment of field-scale passive
      treatment biochemical reactors.
AB  - Anaerobic biochemical reactors (BCRs) are useful for removing metals from mining
      impacted water at remote sites. Removal processes include sorption and
      precipitation of metal sulfides, carbonates, and hydroxides. A question of
      interest is whether BCRs remove aquatic toxicity. Influent and effluent samples
      from the Luttrell Repository and Peerless Jenny King, both in Montana, USA; Park
      City, Utah, USA; and Standard Mine, Colorado, USA, were examined and compared for
      removal of metals and aquatic toxicity. Effluent samples from Standard Mine
      included those having solely BCR treatment and those having BCR treatment
      followed by aeration in a polishing cell. Metal removal for all sites was >90%.
      All influent samples were acutely toxic to Ceriodaphnia dubia and Pimephales
      promelas; toxicity was removed following treatment, except in the Luttrell
      Repository and Standard Mine BCR samples. Laboratory aeration of undiluted
      samples eliminated (Standard Mine BCR) or significantly reduced (Luttrell
      Repository, 65% survival) acute toxicity, most likely through removal of hydrogen
      sulfide. A toxicity identification evaluation suggested that metals also might be
      contributing to toxicity in the Luttrell Repository effluent samples; metals
      other than Mn were either not detected or very low (Fe and Pb) in the Standard
      Mine BCR samples. Field-aerated samples were not acutely toxic, and only the
      Luttrell Repository and Standard Mine samples showed short-term subchronic
      toxicity. Overall, results indicated BCR treatment had high metal removal
      efficiency and that inclusion of in-field aeration was beneficial in removal of
      acute and short-term subchronic toxicity.

PMID- 21072839
TI  - Measuring the toxicity of alkyl-phenanthrenes to early life stages of medaka
      (Oryzias latipes) using partition-controlled delivery.
AB  - Alkyl-phenanthrenes are a class of compounds present in crude oil and toxic to
      developing fish. Most research on alkyl-phenanthrenes has focused on retene (7
      isopropyl-1-methyl-phenanthrene), but little is known about the chronic toxicity
      of related congeners to the early life stages of fish. This project is the first
      to describe the chronic toxicity of a series of alkyl-phenanthrenes to the
      embryos of Japanese medaka (Oryzias latipes) using the partition-controlled
      delivery (PCD) method of exposure and is the first to establish a relationship
      between toxicity of alkyl-phenanthrenes and log P. With PCD, test concentrations
      were maintained by equilibrium partitioning of test chemicals from
      polydimethylsiloxane (PDMS) films containing various concentrations of C1 to C4
      phenanthrenes. Log film:solution partition constants (log K(fs)) and aqueous
      solubility limits were determined for each alkyl-phenanthrene. The prevalence of
      abnormalities in fish embryos increased in an exposure-dependent manner, with
      median effective concentration (EC50) values lower than experimental solubility
      limits of the compounds, and typical of environmental concentrations. Alkyl
      phenanthrenes were more toxic to medaka embryos than unsubstituted phenanthrene,
      with effects resembling those of dioxin and indicating a specific receptor-based
      mechanism of toxicity. These results extend conclusions for the Exxon Valdez oil
      spill, suggest a specific mechanism of toxicity for alkyl-phenanthrenes, and
      provide a model for assessing the risks of mixture toxicity.

PMID- 21072840
TI  - Systems biology: leading the revolution in ecotoxicology.
AB  - The rapid development of new technologies such as transcriptomics, proteomics,
      and metabolomics (Omics) are changing the way ecotoxicology is practiced. The
      data deluge has begun with genomes of over 65 different aquatic species that are
      currently being sequenced, and many times that number with at least some level of
      transcriptome sequencing. Integrating these top-down methodologies is an
      essential task in the field of systems biology. Systems biology is a biology
      based interdisciplinary field that focuses on complex interactions in biological
      systems, with the intent to model and discover emergent properties of the system.
      Recent studies demonstrate that Omics technologies provide valuable insight into
      ecotoxicity, both in laboratory exposures with model organisms and with animals
      exposed in the field. However, these approaches require a context of the whole
      animal and population to be relevant. Powerful approaches using reverse
      engineering to determine interacting networks of genes, proteins, or biochemical
      reactions are uncovering unique responses to toxicants. Modeling efforts in
      aquatic animals are evolving to interrelate the interacting networks of a system
      and the flow of information linking these elements. Just as is happening in
      medicine, systems biology approaches that allow the integration of many different
      scales of interaction and information are already driving a revolution in
      understanding the impacts of pollutants on aquatic systems.

PMID- 21072841
TI  - Review of recent proteomic applications in aquatic toxicology.
AB  - Over the last decade, the environmental sciences have witnessed an incredible
      movement towards the utilization of high-throughput molecular tools that are
      capable of detecting simultaneous changes of hundreds, and even thousands, of
      molecules and molecular components after exposure of organisms to different
      environmental stressors. These techniques have received a great deal of attention
      because they not only offer the potential to unravel novel mechanisms of
      physiological and toxic action but are also amenable to the discovery of
      biomarkers of exposure and effects. In this article, we review the state of
      knowledge of one of these tools in ecotoxicological research: proteomics. We
      summarize the state of proteomics research in fish, and follow with studies
      conducted with aquatic invertebrates. A brief discussion on proteomic methods is
      also presented. We conclude with some ideas for future proteomic studies with
      fish and aquatic invertebrates.

PMID- 21072844
TI  - Effluent-dominated streams. Part 1: Presence and effects of excess nitrogen and
      phosphorus in Wascana Creek, Saskatchewan, Canada.
AB  - Regina, Saskatchewan, Canada (population 190,400) treats its sewage at a modern
      sewage treatment plant (STP) on Wascana Creek. In the winter, treated sewage
      effluent makes up almost 100% of stream flow. Four surveys conducted from 2005 to
      2007, in differing seasons, indicated significantly higher nitrogen (N) and
      phosphorus (P) concentrations at sites downstream of the STP compared to an
      upstream control site. Downstream, Wascana Creek is N hypersaturated (total
      dissolved N >3 mg/L) and soluble reactive phosphorus (SRP) makes up a greater
      percentage of total P (TP). Diminished nutrient retention capacities for both N
      and P are directly attributable to STP effluent. Creek SRP concentrations are
      less than estimates of equilibrium P concentrations (EPC(o)), indicating that
      creek sediments may be a source of P, further exacerbating hypereutrophic ambient
      SRP concentrations. As well, NO(2) + NO(3)-N concentrations far surpass World
      Health Organization limits for drinking water (10 mg/L) and sensitive taxa, while
      NH(3)-N, NH(4)-N, and NO(2) + NO(3)-N exceed Canadian Water Quality Guidelines
      for Protection of Aquatic Life and those for the U.S. Environmental Protection
      Agency. High NH(4)-N concentrations may be responsible for depressions not only
      in algal biomass and production observed downstream but reductions in primary to
      bacterial production ratios (PP:BP). In spring and fall, these reductions push
      PP:BP from net autotrophy to heterotrophy. The Wascana Creek study highlights the
      considerable problems associated with excess nutrients in effluent-dominated
      ecosystems (EDS). It also underlines the need for better controls on NH(4)-N
      additions from STPs in such EDS, especially in a day and age when freshwater
      supplies are dwindling and negative effects of climate change are expected.

PMID- 21072843
TI  - Genomic approaches with natural fish populations from polluted environments.
AB  - Transcriptomics and population genomics are two complementary genomic approaches
      that can be used to gain insight into pollutant effects in natural populations.
      Transcriptomics identify altered gene expression pathways, and population
      genomics approaches more directly target the causative genomic polymorphisms.
      Neither approach is restricted to a predetermined set of genes or loci. Instead,
      both approaches allow a broad overview of genomic processes. Transcriptomics and
      population genomic approaches have been used to explore genomic responses in
      populations of fish from polluted environments and have identified sets of
      candidate genes and loci that appear biologically important in response to
      pollution. Often differences in gene expression or loci between polluted and
      reference populations are not conserved among polluted populations, suggesting a
      biological complexity that we do not yet fully understand. As genomic approaches
      become less expensive with the advent of new sequencing and genotyping
      technologies, they will be more widely used in complementary studies. However,
      although these genomic approaches are immensely powerful for identifying
      candidate genes and loci, the challenge of determining biological mechanisms that
      link genotypes and phenotypes remains.

PMID- 21072845
TI  - Effluent-dominated streams. Part 2: Presence and possible effects of
      pharmaceuticals and personal care products in Wascana Creek, Saskatchewan,
      Canada.
AB  - Recent worldwide surveys have not only established incomplete removal of
      pharmaceuticals and personal care products (PPCPs) by sewage treatment plants,
      but also their presence in surface waters receiving treated sewage effluent.
      Those aquatic systems where sewage effluent dominates flow are thought to be at
      the highest risk for ecosystem level changes. The city of Regina, Saskatchewan,
      Canada (population 190,400) treats its sewage at a modern tertiary sewage
      treatment facility located on Wascana Creek. The Wascana Creek hydrograph is
      dominated by one major event: spring snow melt. Thereafter, creek flow declines
      considerably and in winter treated sewage effluent makes up almost 100% of stream
      flow. Four water surveys conducted on the creek from winter 2005 to spring 2007
      indicated that PPCPs were always present, in nanogram and sometimes microgram per
      liter concentrations downstream of the sewage treatment plant. This mixture
      included antibiotics, analgesics, antiinflammatories, a lipid regulator,
      metabolites of caffeine, cocaine and nicotine, and an insect repellent. Not
      surprisingly, concentrations of some PPCPs were highest in winter. According to
      hazard quotient calculations and homologue presence, ibuprofen, naproxen,
      gemfibrozil, triclosan, erythromycin, trimethoprim, and sulfamethoxazole were
      present in Wascana Creek at concentrations that may present a risk to aquatic
      organisms. The continual exposure to a mixture of pharmaceuticals as well as
      concentrations of un-ionized ammonia that far exceed Canadian and American water
      quality guidelines suggests that Wascana Creek should be considered an ecosystem
      at risk. Although the Wascana Creek study is regional in nature, the results
      highlight the considerable risks posed to aquatic organisms in such effluent
      dominated ecosystems.

PMID- 21072847
TI  - Expression of mucin (MUC) genes in mucoepidermoid carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: Mucoepidermoid carcinoma (MEC) is the most common
      malignant salivary gland tumor. The presence of mucin (MUC) genes has been
      correlated with patient prognosis using immunohistochemical techniques. This
      study was undertaken to 1) investigate the expression of newly discovered MUC
      genes in MEC specimens, 2) assess the correlation of this expression to
      prognosis, and 3) further investigate the correlation of previously identified
      MUC genes to prognosis using molecular techniques. STUDY DESIGN: Retrospective
      chart review and sample isolation. METHODS: Twenty-three patients with a
      diagnosis of MEC underwent mucin gene analysis of tumor and normal surrounding
      salivary gland tissue. Initial expression analysis of recently identified mucin
      genes MUC 12, 13, 17, 18, and 19 was performed using reverse transcription
      polymerase chain reaction (RT-PCR) followed by quantitative assessment with
      quantitative PCR. Additional assessments of mucin genes MUC 1 and MUC 4, which
      have previously been associated with MEC, were also analyzed with real-time RT
      PCR. RESULTS: MEC was associated with MUC 19 expression in 65% of tumor samples
      compared to only 26% of normal tissue (P = .02). MUC 18 demonstrated equal
      expression in both tumor and normal tissue. MUC 12 and 17 were not expressed in
      either MEC or normal salivary gland. MUC 13 was found in 13% of tumors and 0% of
      normal samples. MUC 1 and MUC 4 were expressed 4.2- and 21-fold higher in stage I
      disease in tumor tissue compared to normal, respectively. CONCLUSIONS: Presence
      of MUC 19 is suggestive of mucoepidermoid carcinoma, and higher expression of MUC
      1 and MUC 4 is correlated with earlier stage disease.

PMID- 21072849
TI  - Prognostic importance of the gross classification of hepatocellular carcinoma in
      living donor-related liver transplantation.
AB  - BACKGROUND: The gross classification of hepatocellular carcinoma (HCC) has been
      reported to be a significant prognostic factor for patients with HCC undergoing
      partial hepatectomy. The present study investigated whether the gross
      classification of HCC is also a prognostic factor in living donor-related liver
      transplantation (LDLT). METHODS: Some 119 patients undergoing LDLT for HCC were
      identified retrospectively from a prospective institutional database containing
      information on all LDLTs carried out between 1996 and 2009. Patients were divided
      into three groups according to the gross classification of the largest tumour in
      the explanted liver: type 1 HCC, single nodular type (81 patients); type 2,
      single nodular type with extranodular growth (21); and type 3, contiguous
      multinodular type (17). Clinicopathological factors and recurrence-free survival
      rates were compared. RESULTS: Recurrence-free survival rates for the whole group
      were 87.7 per cent at 1 year, 83.5 per cent at 3 years and 81.0 per cent at 5
      years after LDLT. Type 3 HCC was associated with large tumour size, poor
      histological grade, a high incidence of microvascular invasion and multiple
      tumours. Independent predictors of poor recurrence-free survival were
      preoperative serum level of des-gamma-carboxy prothrombin exceeding 300 mAU/ml,
      microvascular invasion and type 3 HCC. CONCLUSION: The gross classification of
      HCC was an independent predictor for recurrence of HCC in patients undergoing
      LDLT.

PMID- 21072851
TI  - Linking molecular biomarkers with higher level condition indicators to identify
      effects of copper exposures on the endangered delta smelt (Hypomesus
      transpacificus).
AB  - The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species
      endemic to the Sacramento-San Joaquin estuary (CA, USA), and considered an
      indicator of ecosystem health. Copper is a contaminant of concern in Californian
      waterways that may affect the development and survival of this endangered
      species. The experimental combination of molecular biomarkers with higher level
      effects may allow for interpretation of responses in a functional context that
      can be used to predict detrimental outcomes caused by exposure. A delta smelt
      microarray was developed and applied to screen for candidate molecular biomarkers
      that may be used in monitoring programs. Functional classifications of microarray
      responses were used along with quantitative polymerase chain reaction determining
      effects upon neuromuscular, digestive, and immune responses in Cu-exposed delta
      smelt. Differences in sensitivity were measured between juveniles and larvae
      (median lethal concentration = 25.2 and 80.4 ug/L Cu(2+), respectively). Swimming
      velocity declined with higher exposure concentrations in a dose-dependent manner
      (r =  -0.911, p < 0.05), though was not statistically significant to controls.
      Genes encoding for aspartoacylase, hemopexin, alpha-actin, and calcium regulation
      proteins were significantly affected by exposure and were functionally
      interpreted with measured swimming responses. Effects on digestion were measured
      by upregulation of chitinase and downregulation of amylase, whereas
      downregulation of tumor necrosis factor indicated a probable compromised immune
      system. Results from this study, and many others, support the use of functionally
      characterized molecular biomarkers to assess effects of contaminants in field
      scenarios. We thus propose that to attribute environmental relevance to molecular
      biomarkers, research should concentrate on their application in field studies
      with the aim of assisting monitoring programs.

PMID- 21072852
TI  - Stepwise identification of HLA-A*0201-restricted CD8+ T-cell epitope peptides
      from herpes simplex virus type 1 genome boosted by a StepRank scheme.
AB  - Identification of immunodominant epitopes is the first step in the rational
      design of peptide vaccines aimed at T-cell immunity. To date, however, it is yet
      a great challenge for accurately predicting the potent epitope peptides from a
      pool of large-scale candidates with an efficient manner. In this study, a method
      that we named StepRank has been developed for the reliable and rapid prediction
      of binding capabilities/affinities between proteins and genome-wide peptides. In
      this procedure, instead of single strategy used in most traditional epitope
      identification algorithms, four steps with different purposes and thus different
      computational demands are employed in turn to screen the large-scale peptide
      candidates that are normally generated from, for example, pathogenic genome. The
      steps 1 and 2 aim at qualitative exclusion of typical nonbinders by using
      empirical rule and linear statistical approach, while the steps 3 and 4 focus on
      quantitative examination and prediction of the interaction energy profile and
      binding affinity of peptide to target protein via quantitative structure-activity
      relationship (QSAR) and structure-based free energy analysis. We exemplify this
      method through its application to binding predictions of the peptide segments
      derived from the 76 known open-reading frames (ORFs) of herpes simplex virus type
      1 (HSV-1) genome with or without affinity to human major histocompatibility
      complex class I (MHC I) molecule HLA-A*0201, and find that the predictive results
      are well compatible with the classical anchor residue theory and perfectly match
      for the extended motif pattern of MHC I-binding peptides. The putative epitopes
      are further confirmed by comparisons with 11 experimentally measured HLA-A*0201
      restrcited peptides from the HSV-1 glycoproteins D and K. We expect that this
      well-designed scheme can be applied in the computational screening of other viral
      genomes as well.

PMID- 21072853
TI  - Beta-branched residues adjacent to GG4 motifs promote the efficient association
      of glycophorin A transmembrane helices.
AB  - Protein transmenembrane (TM) segments participating in helix-helix packing
      commonly contain small residue patterns (termed GG4 or "small-xxx-small" motifs)
      at i and i + 4 positions. Within many TM segments - such as the glycophorin A
      (GpA) sequence L75IxxGVxxGVxxT87- the G17y-xxx-Gly83 motif often occurs in
      combination with large, usually beta3-branched aliphatic residues at adjacent
      positions, typified here by Val30 and Val84 residues. To explore the importance
      of local P-branched character on GpA dimerization, we made systematic
      replacements to all 16 combinations of single or double Ile, Leu, and AIa
      residues at GpA TM Val/Val positions 80 and 84. Using the TOXCAT system to assay
      self-oligomerization in the Escherichia coli inner membrane--we observed that (i)
      combinations of Val and lie residues maintained, or improved dimerization levels;
      (ii) single Ala or Leu mutant combinations with Val or Ile maintained near-wild
      type dimerization affinities; and (iii) in the absence of beta-branching, i.e.,
      Leu/Leu, Ala/Ala and Ala/Leu combinations, GpA dimerization was significantly
      diminished. An apparent capacity of lle-containing mutants to increase GpA
      dimerization versus WT likely arises from improved van der Waals packing (vs.
      Val) within the locus of helix contact, consistent with correlations we noted in
      lipid accessibility measurements. Examination of several synthetic peptides with
      sequences corresponding to selected GpA mutants (VV VI, IV II, and LL) confirmed
      their dimerization on sodium dodecylsulfate polyacrylamide gel electrophoresis
      (SDS-PAGE). The overall results reinforce the importance of a beta-branch
      containing "ridge" residue to complement a "small-xxx-small groove" in promotion
      of TM-TM interactions.

PMID- 21072854
TI  - Structural study of an active analog of EX-4 in solution and micelle associated
      states.
AB  - Of many drug candidates designed for treatment of type II diabetes, an exendin-4
      (EX-4) analog from the substitutions of both beta-Asp for Glu3 and Tyrfor Glnl3
      of EX-4 was found to have a prolongation in biological half life, an increase in
      cell proliferation and a remarkable improvement in reducing blood glucose with
      respect to EX-4. In this study, we applied CD and NMR approaches to characterize
      the structures of this active EX-4 analog in water, trifluoroethanol (TFE)
      aqueous solution, and dodecylphosphocholine (DPC) micelles and compared the
      results of the EX-4 analog with those of EX-4. Both EX-4 peptides adopt alpha
      helix structures with the N-termini disordered and the C-terminal parts folded as
      hydrophobic clusters in these media. However, the analog has a longer helical
      extension in the N-terminal part than EX-4. The increasing helical turns may
      favor affinity for extracellular domain of glucagon-like peptide-1 receptor and
      accurate positioning of the crucial N-terminal residues in the transmembrane
      domains of the receptor. The analog has a stronger propensity to aggregate than
      the native EX-4, which is attributed to more coiled-coil interaction in the
      analog than in its native type. We also probed the association of EX-4 and its
      analog to DPC micelles and observed micelle-induced insertion of both peptides
      with their N- and C-termini as well as the central parts embedded in micelles and
      the residues near Asp9 and the residues around Trp25-Ser32 more water exposed. A
      single-step ligand-receptor binding model was suggested based on the analysis of
      these results.

PMID- 21072855
TI  - A novel computational approach "BP-STOCH" to study ligand binding to finite
      lattice.
AB  - We report a novel computational algorithm "BP-STOCH" to be used for studying
      single-type ligand binding with biopolymers of finite lengths, such as DNA
      oligonucleotides or oligopeptides. It is based on an idea to represent any type
      of ligand-biopolymer complex in a form of binary number, where "0" and "1" bits
      stand for vacant and engaged monomers of the biopolymer, respectively. Cycling
      over all binary numbers from the lowest 0 up to the highest 2(N) - 1 means a
      sequential generating of all possible configurations of vacant/engaged monomers,
      which, after proper filtering, results in a full set of possible types of
      complexes in solution between the ligand and the N-site lattice. The principal
      advantage of BP-STOCH algorithm is the possibility to incorporate into this cycle
      any conditions on computation of the concentrations and observed experimental
      parameters of the complexes in solution, and programmatic access to each monomer
      of the biopolymer within each binding site of every binding configuration. The
      latter is equivalent to unlimited extension of the basic reaction scheme and
      allows to use BP-STOCH algorithm as an alternative to conventional computational
      approaches.

PMID- 21072860
TI  - Statistical approach to determine the effect of combined environmental parameters
      on conidial development of Trichoderma atroviride (T-15603.1).
AB  - Trichoderma atroviride (T-15603.1) is a promising fungal agent for biological
      control of wood decay fungi in urban tree wounds. The aim of this work was to
      determine the combined effects of water activity (a(w), 0.998-0.892), temperature
      (10-30  degrees C) and pH (3-7) on the development of conidia on low-nutrient
      agar (LNA). Lag phase prior to germination (h), germination rates (u(m)) and germ
      tube elongation were obtained at each set of conditions. The experimental data
      were used to fit a response surface model for predicting the germination rates of
      T-15603.1 and to analyze the effect of the abiotic parameters tested. The
      polynomial response surface model was mathematically evaluated using graphical
      plots and several statistical indices (RMSE, %SEP, A(f), B(f), pRE). Data
      analyses showed a highly significant effect on conidial development of a(w) and
      temperature (P < 0.001), whereas no significant effect of pH (P >= 0.05) was
      observed. The germination rate dropped and the lag prior to germination increased
      as the temperature and a(w) decreased, but T-15603.1 appeared to be more
      sensitive to a(w) reduction than to temperature. The minimum a(w) level for
      germination was 0.910 at 15-25  degrees C, and maximum germination rates were
      obtained at a(w) = 0.998, 25-30  degrees C and pH 5. The response surface model
      was useful and widely accurate (R2 = 0.983) for predicting the germination rate
      of T-15603.1 and complemented the experimental results. These findings contribute
      to better understanding how combined environmental factors affect the
      environmental parameter tolerance levels of T-15603.1 and to the development of
      an adequate delivery system for optimized application of T-15603.

PMID- 21072861
TI  - Metabolic changes of Acidithiobacillus caldus under Cu2(+) stress.
AB  - Metabolic changes were investigated by measuring the depletion of dissolved
      oxygen and the enzymatic activities of sulfur metabolism in Acidithiobacillus
      caldus (A. caldus) before and after copper stress. The results showed that high
      concentrations of Cu2(+) have an indirect negative effect on the sulfite oxidase
      and the APS reductase involved in sulfur metabolism when A. caldus is cultured in
      medium with elemental sulfur as its growth energy. This leads to a decrease in
      the respiration rate and the growth rate. The changes of activity are negatively
      correlated with the intracellular Cu2(+) concentration through an indirect
      interaction mechanism. A. caldus was able to induce an efflux of copper ions by
      forming an ATPase-dependent pump, which transported copper ions by consuming ATP.
      The negative effect of Cu2(+) on the bacterial metabolism could be minimized by
      the copper efflux when the bacteria were adapted in medium containing Cu2(+) for
      a long time. However, this bacterial rejuvenation became weaker when grown in
      medium containing higher concentrations of copper ions.

PMID- 21072864
TI  - Multiple stable states with in-plane anisotropy in ultrathin YMnO3 films.

PMID- 21072867
TI  - Microfluidic devices for bioapplications.
AB  - Harnessing the ability to precisely and reproducibly actuate fluids and
      manipulate bioparticles such as DNA, cells, and molecules at the microscale,
      microfluidics is a powerful tool that is currently revolutionizing chemical and
      biological analysis by replicating laboratory bench-top technology on a miniature
      chip-scale device, thus allowing assays to be carried out at a fraction of the
      time and cost while affording portability and field-use capability. Emerging from
      a decade of research and development in microfluidic technology are a wide range
      of promising laboratory and consumer biotechnological applications from
      microscale genetic and proteomic analysis kits, cell culture and manipulation
      platforms, biosensors, and pathogen detection systems to point-of-care diagnostic
      devices, high-throughput combinatorial drug screening platforms, schemes for
      targeted drug delivery and advanced therapeutics, and novel biomaterials
      synthesis for tissue engineering. The developments associated with these
      technological advances along with their respective applications to date are
      reviewed from a broad perspective and possible future directions that could arise
      from the current state of the art are discussed.

PMID- 21072868
TI  - Polymer nanotubules obtained by layer-by-layer deposition within AAO-membrane
      templates with sub-100-nm pore diameters.

PMID- 21072869
TI  - Nanogeometry matters: unexpected decrease of capillary adhesion forces with
      increasing relative humidity.
AB  - The sticking effect between hydrophilic surfaces occurring at increasing relative
      humidity (RH) is an everyday phenomenon with uncountable implications. Here
      experimental evidence is presented for a counterintuitive monotonous decrease of
      the capillary adhesion forces between hydrophilic surfaces with increasing RH for
      the whole humidity range. It is shown that this unexpected result is related to
      the actual shape of the asperity at the nanometer scale: a model based on
      macroscopic thermodynamics predicts this decrease in the adhesion force for a
      sharp object ending in an almost flat nanometer-sized apex, in full agreement
      with experiments. This anomalous decrease is due to the fact that a significant
      growth of the liquid meniscus formed at the contact region with increasing
      humidity is hindered for this geometry. These results are relevant in the
      analysis of the dynamical behavior of nanomenisci. They could also have an
      outstanding value in technological applications, since the undesirable sticking
      effect between surfaces occurring at increasing RH could be avoided by
      controlling the shape of the surface asperities at the nanometric scale.

PMID- 21072870
TI  - Encapsulation and release of molecular cargos via temperature-induced vesicle-to
      micelle transitions.
AB  - Temperature-induced vesicle-to-micelle transitions of polystyrene-block-poly
      acrylic acid (PS(139)-b-PAA(17)) aggregates in tetrahydrofuran (THF)/H(2)O
      solvent mixtures are studied. For a typical system with an initial concentration
      of PS(139)-b-PAA(17) of 2 wt% and 50 vol% of H(2)O, the morphology of the
      aggregates changes from vesicles to micelles upon heating from room temperature
      to 45  degrees C. The transition temperature is found to depend on the polymer
      concentration as well as solvent composition. A higher polymer concentration
      results in a higher transition temperature. The morphological change is
      attributed to a change in the solvent-polymer interactions, which results in a
      reduction in interfacial energy. The corresponding temperature-induced
      morphological change is employed as a strategy for the reversible release and
      encapsulation of small molecules. The release of Rhodamine 110 bisamide above the
      transition temperature is observed as a result of the trypsin-catalyzed
      hydrolysis of the bisamide into Rhodamine 110. Likewise, the successful
      encapsulation of Rhodamine 110 below the transition temperature is proven using
      sodium nitrite as a chemical quencher.

PMID- 21072871
TI  - Programmed nanopatterning of organic/inorganic nanoparticles using nanometer
      scale wells embedded in a DNA origami scaffold.

PMID- 21072873
TI  - TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by
      flagellin.
AB  - The fact that some TLR-based vaccine adjuvants maintain function in TLR-deficient
      hosts highlights that their mechanism of function remains incompletely
      understood. Thus, we examined the ability of flagellin to induce cytokines and
      elicit/promote murine antibody responses upon deletion of the flagellin receptors
      TLR5 and/or NLRC4 (also referred to as IPAF) using a prime/boost regimen. In TLR5
      KO mice, flagellin failed to induce NF-kappaB-regulated cytokines such as
      keratinocyte-derived chemokine (CXCL1) but induced WT levels of the inflammasome
      cytokine IL-18 (IL-1F4). Conversely, in NLRC4-KO mice, flagellin induced
      keratinocyte-derived chemokine, but not IL-18, whereas TLR5/NLRC4-DKO lacked
      induction of all cytokines measured. Flagellin/ovalbumin treatment resulted in
      high-antibody titers to both flagellin and ovalbumin in WT, TLR5-KO and DKO mice
      but did not elicit antibodies to either in TLR5/NLRC4-DKO mice. Thus, flagellin's
      ability to elicit/promote humoral immunity requires a germ-line-encoded receptor
      capable of recognizing this molecule. Such promotion of adaptive immunity can be
      effectively driven by either TLR5-mediated activation of NF-kappaB or NLRC4
      mediated activation of the inflammasome.

PMID- 21072874
TI  - Generation of TRAIL-receptor 1-specific human monoclonal Ab by a combination of
      immunospot array assay on a chip and human Ab-producing mice.

PMID- 21072880
TI  - Memory-like IFN-gamma response by NK cells following malaria infection reveals
      the crucial role of T cells in NK cell activation by P. falciparum.
AB  - NK cells are rapid IFN-gamma responders to Plasmodium falciparum-infected
      erythrocytes (PfRBC) in vitro and are involved in controlling early parasitaemia
      in murine models, yet little is known about their contribution to immune
      responses following malaria infection in humans. Here, we studied the dynamics of
      and requirements for in vitro NK responses to PfRBC in malaria-naive volunteers
      undergoing a single experimental malaria infection under highly controlled
      circumstances, and in naturally exposed individuals. NK-specific IFN-gamma
      responses to PfRBC following exposure resembled an immunological recall pattern
      and were tightly correlated with T-cell responses. However, although PBMC
      depleted of CD56(+) cells retained 20-55% of their total IFN-gamma response to
      PfRBC, depletion of CD3(+) cells completely abrogated the ability of remaining
      PBMC, including NK cells, to produce IFN-gamma. Although NK responses to PfRBC
      were partially dependent on endogenous IL-2 signaling and could be augmented by
      exogenous IL-2 in whole PBMC populations, this factor alone was insufficient to
      rescue NK responses in the absence of T cells. Thus, NK cells make a significant
      contribution to total IFN-gamma production in response to PfRBC as a consequence
      of their dependency on (memory) T-cell help, with likely positive implications
      for malaria vaccine development.

PMID- 21072887
TI  - Efficient Treg depletion induces T-cell infiltration and rejection of large
      tumors.
AB  - There are a number of factors that hamper immunotherapy of cancer. For example,
      tumors exhibit an aberrant vasculature that appears to form a barrier against T
      cell infiltration. Another major obstacle is created by Treg. So far,
      conventional depletion of Treg with anti-CD25 antibodies, which eliminate only
      70% of Treg, has failed to significantly reduce the growth of established tumors.
      Using Foxp3.LuciDTR-4 mice, we show here that 90-95% Treg depletion resulted in
      complete regression of large established tumors, whereas 70% depletion was
      ineffective. The extensive Treg depletion induced a number of processes that are
      critical for tumor rejection, including activation of tumor-specific CD8(+) T
      cells and enhanced infiltration of these cells into the tumor. The precise
      mechanism of enhanced infiltration is not known, but normalization of the tumor
      vasculature is assumed to assist infiltration. Indeed, we observed that 90% Treg
      depletion caused normalization of the tumor vasculature as indicated by a
      reduction in leakiness and the number of dilated vessels. These results suggest
      that for clinical immunotherapy of cancer, it would be desirable to have reagents
      that allow high-level depletion of Treg, which, in conjunction with treatment
      modalities such as vaccination, may concomitantly increase T-cell activation and
      infiltration.

PMID- 21072888
TI  - Sphincteroplasty for fecal incontinence in the era of sacral nerve modulation.
AB  - The role of sphincteroplasty in the treatment of patients with fecal incontinence
      due to anal sphincter defects has been questioned because the success rate
      declines in the long-term. A new emerging treatment for fecal incontinence,
      sacral nerve stimulation, has been shown to be effective in these patients.
      However, the success rate of sphincteroplasty may depend of several patient
      related and surgical-related factors and the outcome from sphincteroplasty has
      been evaluated differently (with qualitative data) from that after sacral nerve
      stimulation (quantitative data using scoring systems and quality of life).
      Furthermore, the data available so far on the long-term success rate after sacral
      nerve modulation do not differ substantially from those after sphincteroplasty.
      The actual data do not support the replacement of sphincteroplasty with sacral
      nerve stimulation in patients with fecal incontinence secondary to sphincter
      defects.

PMID- 21072889
TI  - Non-invasive markers of gut wall integrity in health and disease.
AB  - The intestinal mucosa is responsible for the absorption of nutrients from the
      lumen and for the separation of the potentially toxic luminal content (external
      environment) from the host (internal environment). Disruption of this delicate
      balance at the mucosal interface is the basis for numerous (intestinal) diseases.
      Experimental animal studies have shown that gut wall integrity loss is involved
      in the development of various inflammatory syndromes, including post-operative or
      post-traumatic systemic inflammatory response syndrome, sepsis, and multiple
      organ failure. Assessment of gut wall integrity in clinical practice is still a
      challenge, as it is difficult to evaluate the condition of the gut non-invasively
      with currently available diagnostic tools. Moreover, non-invasive, rapid
      diagnostic means to assess intestinal condition are needed to evaluate the
      effects of treatment of intestinal disorders. This review provides a survey of
      non-invasive tests and newly identified markers that can be used to assess gut
      wall integrity.

PMID- 21072890
TI  - Pediatric nonalcoholic fatty liver disease: overview with emphasis on histology.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a disease in which excessive fat
      accumulates in the liver of a patient without a history of alcohol abuse. This
      disease includes simple steatosis and nonalcoholic steatohepatitis (NASH).
      NAFLD/NASH is recognized as a hepatic manifestation of metabolic syndrome. In
      recent years, pediatric NAFLD has increased in line with the increased prevalence
      of pediatric obesity. The estimated prevalence of pediatric NAFLD is 2.6%-9.6%,
      and it is associated with sex, age, and ethnicity. With regard to the
      pathogenesis of NAFLD, the "two-hit" hypothesis is widely accepted and oxidative
      stress is thought to play an important role in the second hit. Although clinical
      symptoms, laboratory data, and imaging findings are important, liver biopsy is
      regarded as the gold standard for the diagnosis of NAFLD/NASH. In addition, liver
      biopsy is essential for assessing the degree of necro-inflammatory change and
      fibrosis in NASH. Two different types of steatohepatitis (type 1 and type 2 NASH)
      have been reported, with type 2 NASH being present in as many as 51% of pediatric
      NAFLD patients. However, we and others have observed that type 1 and 2 patterns
      commonly overlap. Although pharmacotherapy has been studied in clinical trials,
      lifestyle modification by diet and exercise remains the mainstay of treatment for
      NAFLD/NASH.

PMID- 21072891
TI  - Histopathology of nonalcoholic fatty liver disease.
AB  - Histological analysis of liver biopsies remains a standard against which other
      methods of assessment for the presence and amount of hepatic injury due to
      nonalcoholic fatty liver disease (NAFLD) are measured. Histological evaluation
      remains the sole method of distinguishing steatosis from advanced forms of NAFLD,
      i.e. nonalcoholic steatohepatitis (NASH) and fibrosis. Included in the lesions of
      NAFLD are steatosis, lobular and portal inflammation, hepatocyte injury in the
      forms of ballooning and apoptosis, and fibrosis. However, patterns of these
      lesions are as distinguishing as the lesions themselves. Liver injury in adults
      and children due to NAFLD may have different histological patterns. In this
      review, the rationale for liver biopsy, as well as the histopathological lesions,
      the microscopically observable patterns of injury, and the differential diagnoses
      of NAFLD and NASH are discussed.

PMID- 21072892
TI  - Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage
      liver disease.
AB  - AIM: To assess the utility of an autologous CD34(+) and CD133(+) stem cells
      infusion as a possible therapeutic modality in patients with end-stage liver
      diseases. METHODS: One hundred and forty patients with end-stage liver diseases
      were randomized into two groups. Group 1, comprising 90 patients, received
      granulocyte colony stimulating factor for five days followed by autologous
      CD34(+) and CD133(+) stem cell infusion in the portal vein. Group 2, comprising
      50 patients, received regular liver treatment only and served as a control group.
      RESULTS: Near normalization of liver enzymes and improvement in synthetic
      function were observed in 54.5% of the group 1 patients; 13.6% of the patients
      showed stable states in the infused group. None of the patients in the control
      group showed improvement. No adverse effects were noted. CONCLUSION: Our data
      showed that a CD34(+) and CD133(+) stem cells infusion can be used as supportive
      treatment for end-stage liver disease with satisfactory tolerability.

PMID- 21072893
TI  - Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory
      disturbance in rat mesentery.
AB  - AIM: To investigate the effect of total salvianolic acid (TSA) on ischemia
      reperfusion (I/R)-induced rat mesenteric microcirculatory dysfunctions. METHODS:
      Male Wistar rats were randomly distributed into 5 groups (n = 6 each): Sham group
      and I/R group (infused with saline), TSA group, TSA + I/R group and I/R + TSA
      group (infused with TSA, 5 mg/kg per hour). Mesenteric I/R were conducted by a
      ligation of the mesenteric artery and vein (10 min) and subsequent release of the
      occlusion. TSA was continuously infused either starting from 10 min before the
      ischemia or 10 min after reperfusion. Changes in mesenteric microcirculatory
      variables, including diameter of venule, velocity of red blood cells in venule,
      leukocyte adhesion, free radicals released from venule, albumin leakage and mast
      cell degranulation, were observed through an inverted intravital microscope.
      Meanwhile, the expression of adhesion molecules CD11b/CD18 on neutrophils was
      evaluated by flow cytometry. Ultrastructural evidence of mesenteric venules
      damage was assessed after microcirculation observation. RESULTS: I/R led to
      multiple responses in mesenteric post-capillary venules, including a significant
      increase in the adhesion of leukocytes, production of oxygen radicals in the
      venular wall, albumin efflux and enhanced mast cell degranulation in vivo. All
      the I/R-induced manifestations were significantly reduced by pre- or post
      treatment with TSA, with the exception that the I/R-induced increase in mast cell
      degranulation was inhibited only by pre-treatment with TSA. Moreover, pre- or
      post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on
      neutrophils, reducing the increase in the number of caveolae in the endothelial
      cells of mesentery post-capillary venules induced by I/R. CONCLUSION: The results
      demonstrated that TSA protects from and ameliorates the microcirculation
      disturbance induced by I/R, which was associated with TSA inhibiting the
      production of oxygen-free radicals in the venular wall and the expression of
      CD11b/CD18 on neutrophils.

PMID- 21072894
TI  - Antibiotic prophylaxis in variceal hemorrhage: timing, effectiveness and
      Clostridium difficile rates.
AB  - AIM: To investigate if antibiotics administered within 8 h of endoscopy reduce
      mortality or increase the incidence of Clostridium difficile infection (CDI).
      METHODS: A 2-year retrospective analysis of all patients who presented with first
      variceal hemorrhage was undertaken. The primary outcome measure was 28-d
      mortality. Secondary outcome measures were 28-d rebleeding rates and 28-d
      incidence of CDI. All patients were admitted to a tertiary liver unit with a
      consultant-led, 24-h endoscopy service. Patients received standard care including
      terlipressin therapy. Data collection included: primary and secondary outcome
      measures, timing of first administration of intravenous antibiotics, etiology of
      liver disease, demographics, endoscopy details and complications. A prospective
      study was undertaken to determine the incidence of CDI in the study population
      and general medical inpatients admitted for antibiotic therapy of at least 5 d
      duration. Statistical analysis was undertaken using univariate, non-parametric
      tests and multivariate logistic regression analysis. RESULTS: There were 70 first
      presentations of variceal hemorrhage during the study period. Seventy percent of
      cases were male and 65.7% were due to chronic alcoholic liver disease. In total,
      64/70 (91.4%) patients received antibiotics as prophylaxis during their
      admission. Specifically, 53/70 (75.7%) received antibiotics either before
      endoscopy or within 8 h of endoscopy [peri-endoscopy (8 h) group], whereas 17/70
      (24.3%) received antibiotics at > 8 h after endoscopy or not at all (non peri
      endoscopy group). Overall mortality and rebleeding rates were 13/70 (18.6%) and
      14/70 (20%), respectively. The peri-endoscopy (8 h) group was significantly less
      likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%, P =
      0.04, odds ratio (OR) = 0.28 (0.078-0.997)] and showed a trend towards reduced
      rebleeding [17.0% vs 29.4%, P = 0.27, OR = 0.49 (0.14-1.74)]. On univariate
      analysis, the non peri-endoscopy group [P = 0.02, OR = 3.58 (1.00-12.81)], higher
      model for end-stage liver disease (MELD) score (P = 0.02), presence of
      hepatorenal syndrome [P < 0.01, OR = 11.25 (2.24-56.42)] and suffering a clinical
      episode of sepsis [P = 0.03, OR = 4.03 (1.11-14.58)] were significant predictors
      of death at 28 d. On multivariate logistic regression analysis, lower MELD score
      [P = 0.01, OR = 1.16 (1.04-1.28)] and peri-endoscopy (8 h) group [P = 0.01, OR =
      0.15 (0.03-0.68)] were independent predictors of survival at 28 d. The CDI
      incidence (5.7%) was comparable to that in the general medical population (5%).
      CONCLUSION: Antibiotics administered up to 8 h following endoscopy were
      associated with improved survival at 28 d. CDI incidence was comparable to that
      in other patient groups.

PMID- 21072895
TI  - Endoscopic mucosal resection of colorectal polyps in typical UK hospitals.
AB  - AIM: To evaluate the outcomes of endoscopic mucosal resection (EMR) for
      colorectal polyps, with particular regard to procedural complications and
      recurrence rate, in typical United Kingdom (UK) hospitals that perform an average
      of about 25 colonic EMRs per year. METHODS: A total of 239 colorectal polyps (>=
      10 mm) resected from 199 patients referred to Rochdale Infirmary, Salford Royal
      Hospital and Royal Oldham Hospital for EMR between January 2003 and January 2009
      were studied. RESULTS: The mean size of polyps resected was 19.6 +/- 12.4 mm
      (range 10-80 mm). The overall major complication rate was 2.1%. Complications
      were less frequent with non-adenomas compared with the other groups (Pearson's
      chi(2) test, P < 0.0001). Resections of larger-sized polyps were more likely to
      result in complications (unpaired t-test, P = 0.021). Recurrence was associated
      with histology, with carcinoma-in-situ more likely to recur compared with low
      grade dysplasia [hazard ratio (HR) 186.7, 95% confidence interval (95% CI): 8.81
      3953.02, P = 0.001]. Distal lesions were also more likely to recur compared with
      right-sided and transverse colon lesions (HR 5.93, 95% CI: 1.35-26.18, P =
      0.019). CONCLUSION: EMR for colorectal polyps can be performed safely and
      effectively in typical UK hospitals. Stricter follow-up is required for
      histologically advanced lesions due to increased recurrence risk.

PMID- 21072896
TI  - Factors associated with incomplete small bowel capsule endoscopy studies.
AB  - AIM: To identify patient risk factors associated with incomplete small bowel
      capsule endoscopy (CE) studies. METHODS: Data from all CE procedures performed at
      St. Paul's Hospital in Vancouver, British Columbia, Canada, between December 2001
      and June 2008 were collected and analyzed on a retrospective basis. Data
      collection for complete and incomplete CE study groups included patient
      demographics as well as a number of potential risk factors for incomplete CE
      including indication for the procedure, hospitalization, diabetes mellitus with
      or without end organ damage, limitations in mobility, renal insufficiency, past
      history of bowel obstruction, abdominal surgery, abdominal radiation therapy and
      opiate use. Risk factors were analyzed using a univariable and multivariable
      logistic regression model. RESULTS: From a total of 535 CE procedures performed,
      158 were incomplete (29.5%). The univariable analysis showed that CE procedures
      performed for overt gastrointestinal bleeding (P = 0.002), and for patients with
      a prior history of abdominal surgery (P = 0.023) or bowel obstruction (P = 0.023)
      were significantly associated with incomplete CE studies. Patients on opiate
      medications (P = 0.094) as well as hospitalized patients (P = 0.054) were not
      statistically significant, but did show a trend towards incomplete CE. The
      multivariable analysis showed that independent risk factors for an incomplete CE
      procedure include prior history of bowel obstruction [odds ratios (OR) 2.77, P =
      0.02, 95% confidence intervals (CI): 1.17-6.56] and procedures performed for
      gastrointestinal bleeding (Occult OR 2.04, P = 0.037, 95% CI: 1.04-4.02 and Overt
      OR 2.69, P = 0.002, 95% CI: 1.44-5.05). Patients with a prior history of
      abdominal surgery (OR 1.46, P = 0.068, 95% CI: 0.97-2.19), those taking opiate
      medications (OR 1.54, P = 0.15, 95% CI: 0.86-2.76) and hospitalized patients (OR
      1.82, P = 0.124, 95% CI: 0.85-3.93) showed a trend towards statistical
      significance. CONCLUSION: We have identified a number of risk factors for
      incomplete CE procedures that can be used to risk-stratify patients and guide
      interventions to improve completion rates.

PMID- 21072897
TI  - MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in
      hepatocellular carcinoma cells.
AB  - AIM: To investigate the proliferative effect of advanced glycation end-products
      (AGEs) and the role of their cellular receptor (RAGE) on hepatocellular carcinoma
      (HCC) cells, and the inhibitory effects of MK615, an extract from Japanese
      apricot, against AGEs were also evaluated. METHODS: Two HCC cell lines, HuH7 and
      HepG2, were used. Expression of RAGE was investigated by polymerase chain
      reaction, Western blotting, and flow cytometry (FACS). The effect of MK615 on
      RAGE expression was also evaluated by FACS. The proliferative effects of a
      control (unglycated bovine serum albumin), glucose-derived AGEs (Glc-AGE), and
      glyceraldehyde-derived AGEs (Glycer-AGE), and the anti-proliferative effect of
      MK615 against AGEs, were evaluated using MTT assays. RESULTS: Expression of RAGE
      was confirmed at both the mRNA and protein levels in both HuH7 and HepG2. FACS
      revealed that the level of RAGE expression was higher in HuH7 than in HepG2.
      Treatment with 0.1 MUg/mL MK615 decreased the expression level of RAGE from 24.3%
      to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2. The growth indices for the
      control, Glc-AGE, and Glycer-AGE were 1.06 +/- 0.08, 0.99 +/- 0.04, and 1.38 +/-
      0.05, respectively, in HuH7 (P = 0.037), and were 1.03 +/- 0.04, 1.04 +/- 0.03,
      and 1.07 +/- 0.05, respectively, in HepG2 (P > 0.05). When the cells were
      cultured simultaneously with Glycer-AGE and MK615, MK615 abrogated the
      proliferative effect of Glycer-AGE in HuH7. CONCLUSION: Only Glycer-AGE has a
      proliferative effect on HuH7, which expresses a higher level of RAGE. MK615
      suppresses the proliferative effect of Glycer-AGE on HuH7 by decreasing the
      expression of RAGE.

PMID- 21072898
TI  - Comparative study of therapeutic effects of PPI and H2RA on ulcers during
      continuous aspirin therapy.
AB  - AIM: To compare the therapeutic effects of proton pump inhibitors (PPI) and
      histamine 2 receptor antagonists (H2RA) on gastroduodenal ulcers under continuous
      use of low-dose aspirin. METHODS: Sixty patients who had a gastroduodenal ulcer
      on screening endoscopy but required continuous use of low-dose aspirin were
      randomly assigned to receive PPI (lansoprazole 30 mg, n = 30) or H2RA (famotidine
      40 mg or if famotidine had been administered before assignment, ranitidine 300
      mg, n = 30). The therapeutic effects were evaluated by endoscopy after 8-wk
      treatment. The presence or absence of Helicobacter pylori (H. pylori) was
      determined by urea breath test before treatment. Abdominal symptoms were compared
      with the gastrointestinal symptom rating scale (GSRS) questionnaire before and
      after treatment. RESULTS: Twenty-six patients in the PPI group and 26 patients in
      the H2RA group, excluding dropouts, were analyzed. There were no significant
      differences in median age, sex, underlying disease, smoking status, H. pylori
      infection, prevalence of ulcers before treatment, and lesion site between the two
      groups. The therapeutic effects were endoscopically evaluated as healed in 23
      patients (88.5%) and not healed in 3 patients in the PPI group and as healed in
      22 patients (84.6%) and not healed in 4 patients in the H2RA group. Abdominal
      symptoms before treatment were uncommon in both groups; the GSRS scores were not
      significantly reduced after treatment as compared with before treatment.
      CONCLUSION: The healing rate of gastroduodenal ulcers during continuous use of
      low-dose aspirin was greater than 80% in both the PPI group and the H2RA group,
      with no significant difference between the two groups.

PMID- 21072899
TI  - Endoscopic management of occluded metal biliary stents: metal versus 10F plastic
      stents.
AB  - AIM: To compare the efficacy of self-expandable metal stents (SEMSs) with 10F
      plastic stents (PSs) in the endoscopic management of occluded SEMSs. METHODS: We
      retrospectively reviewed the medical records of 56 patients who underwent SEMS
      insertion for palliation of unresectable malignant biliary obstruction between
      2000 and 2007 and subsequent endoscopic retrograde biliary drainage (ERBD) with
      SEMS or PS for initial SEMS occlusion between 2000 and 2008. RESULTS: Subsequent
      ERBD with SEMS was performed in 29 patients and with PS in 27. The median time to
      stent occlusion after subsequent ERBD was 186 d in the SEMS group and 101 d in
      the PS group (P = 0.118). Overall median stent patency was 79 d for the SEMS
      group and 66 d for the PS group (P = 0.379). The mean number of additional
      biliary drainage procedures after subsequent ERBD in patients that died (n = 50)
      during the study period was 2.54 +/- 4.12 for the SEMS group and 1.85 +/- 1.95
      for the PS group (P = 0.457). The mean total cost of additional biliary drainage
      procedures after the occlusion of subsequent SEMS or PS was $410.04 +/- 692.60
      for the SEMS group and $630.16 +/- 671.63 for the PS group (P = 0.260). Tumor
      ingrowth as the cause of initial SEMS occlusion was the only factor associated
      with a shorter time to subsequent stent occlusion (101 d for patients with tumor
      ingrowth vs 268 d for patients without tumor ingrowth, P = 0.008). CONCLUSION:
      Subsequent ERBD with PSs offered similar patency and number of additional biliary
      drainage procedures compared to SEMSs in the management of occluded SEMS.

PMID- 21072900
TI  - Predictive factors associated with malignancy of intraductal papillary mucinous
      pancreatic neoplasms.
AB  - AIM: To identify preoperative predictive factors associated with malignancy of
      intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS:
      Between April 1995 and April 2010, 129 patients underwent surgical resection for
      IPMNs at our institute and had confirmed pathologic diagnoses. The medical
      records were retrospectively reviewed and immunohistochemical staining for mucin
      (MUC) in pancreatic tissues was performed. RESULTS: Univariate analysis showed
      that the following five variables were closely associated with malignant IPMNs
      preoperatively: absence of extrapancreatic malignancy; symptoms; tumor size > 4
      cm; main pancreatic duct (MPD) size > 7 mm; and lymph node enlargement on
      preoperative computed tomography (CT). Multivariate analysis revealed that the
      following two factors were significantly associated with malignant IPMNs
      preoperatively: MPD size > 7 mm [odds ratio (OR) = 2.50]; and lymph node
      enlargement on preoperative CT (OR = 3.57). No significant differences in the
      expression of MUC1, MUC2 and MUC5AC were observed between benign and malignant
      IPMNs. CONCLUSION: MPD size > 7 mm and preoperative lymph node enlargement on CT
      are useful predictive factors associated with malignancy of IPMNs.

PMID- 21072901
TI  - Specific intronic p53 mutation in esophageal squamous cell carcinoma in Southern
      Thailand.
AB  - AIM: To investigate p53 mutations in esophageal cancer in a high-risk population,
      and correlate them with smoking, alcohol consumption and betel chewing. METHODS:
      One hundred and sixty-five tumor samples of esophageal squamous cell carcinoma
      (ESCC) obtained from a university hospital in Songkhla province, Southern
      Thailand were investigated for p53 mutations in exons 5-8, using polymerase chain
      reaction-single strand conformation polymorphism analysis, followed by direct
      sequencing. A polymerase chain reaction-restriction fragment length polymorphism
      (RFLP) assay was additionally used to confirm possible germline mutation in
      intron 6. A history of risk habits was obtained by interviews. The association
      between risk habits and mutation frequency was evaluated using the chi(2) test.
      RESULTS: The studied specimens were from 139 male and 26 female patients with
      ESCC, treated at Songklanagarind Hospital. Most of the patients were smokers
      (86.7%) and alcohol consumers (72.73%), and 38.3% were betel chewers. Forty-three
      mutations of the p53 gene were detected in 25.5% (42/165) of tumor samples.
      Mutations were most commonly found in exon 5 (25.6%) and exon 8 (25.6%).
      Mutations in the hot-spot codon 248 were found in four cases (9.3% of all
      mutations). G:C->C:G (30.23%), G:C->A:T (27.90%) and G:C->T:A (16.28%) were the
      prevalent spectra of mutations. Unexpectedly, among 10 intronic mutations, eight
      cases harbored a similar mutation: G->C substitution in intron 6 (nucleotide
      12759, GenBank NC_000017). These were additionally confirmed by the RFLP
      technique. Similar mutations were also detected in their matched blood samples
      using RFLP and direct sequencing, which suggested germline mutations. There was
      no significant correlation between risk habits and p53 mutation frequency.
      CONCLUSION: A proportion of Thai ESCC patients harbored specific intronic p53
      mutations, which might be germline mutations. Further studies are needed to
      explore this novel finding.

PMID- 21072902
TI  - Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for
      radionuclide therapy.
AB  - AIM: To investigate the feasibility of radionuclide therapy of colon tumor cells
      by baculovirus vector-mediated transfer of the sodium/iodide symporter (NIS)
      gene. METHODS: A recombinant baculovirus plasmid carrying the NIS gene was
      constructed, and the viruses (Bac-NIS) were prepared using the Bac-to-Bac system.
      The infection efficiency in the colon cancer cell line SW1116 of a green
      fluorescent protein (GFP) expressing baculovirus (Bac-GFP) at different
      multiplicities of infection (MOI) with various concentrations of sodium butyrate
      was determined by flow cytometry. An in vitro cytotoxicity assay was also
      conducted after infection of SW1116 cells with Bac-NIS. Iodine uptake of Bac-NIS
      infected SW1116 cells and inhibition of this uptake by sodium perchlorate was
      examined, and the effect of Bac-NIS-mediated (131)I in killing tumor cells was
      evaluated by cell colony formation tests. RESULTS: Infection and transgene
      expression in SW1116 with Bac-GFP were significantly enhanced by sodium butyrate,
      as up to 72% of SW1116 cells were infected with the virus at MOI of 400 and
      sodium butyrate at 0.5 mmol/L. No obvious cytotoxicity was observed under these
      conditions. Infection of SW1116 with Bac-NIS allowed uptake of (131)I in these
      tumor cells, which could be inhibited by sodium perchlorate. The viability of
      SW1116 cells infected with Bac-NIS was significantly lower than with Bac-GFP,
      suggesting that NIS gene-mediated (131)I uptake could specifically kill tumor
      cells. CONCLUSION: Baculovirus vector-mediated NIS gene therapy is a potential
      approach for treatment of colon cancer.

PMID- 21072903
TI  - Patterns of lymph node metastasis are different in colon and rectal carcinomas.
AB  - AIM: To describe patterns of lymph node metastasis in invasive colon and rectal
      carcinomas. METHODS: Clinical data of 2340 patients with colorectal carcinoma
      (stage I to III) who received radical resection, was retrospectively reviewed. Of
      the 2340 patients, 1314 patients suffered from rectal carcinoma and 1026 from
      colon carcinoma. Patients with rectal cancer who received neoadjuvant
      chemoradiation therapy were excluded. Statistical analysis was performed using
      Mann-Whitney, chi(2) and Cochran's and Mantel-Haenszel tests (SPSS 15.0). A two
      tailed P < 0.05 was considered statistically significant. RESULTS: Lymph node
      retrieval in the rectal carcinoma group was significantly lower than that in the
      colon carcinoma group (P < 0.001), while positive lymph node retrieval in the
      rectal carcinoma group was significantly higher than that in the colon carcinoma
      group (P < 0.001). The proportion of lymph node positive (N+) cases was higher
      (patients with one or more positive lymph nodes) in the rectal carcinoma group (P
      = 0.004). The number of N+ cases was compared at different T stages (T1-T4) to
      eliminate background bias and the results were confirmed (P < 0.001). In
      addition, the lymph node ratio (the ratio of number of positive lymph nodes over
      the number of lymph nodes examined) of stage III cases in the rectal carcinoma
      group was significantly higher than that in the colon carcinoma group (P <
      0.001). CONCLUSION: Rectal carcinomas seem more prone to metastasize to the lymph
      nodes than colon carcinomas, which may be of potential clinical significance.

PMID- 21072904
TI  - STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer.
AB  - AIM: To investigate the correlation between gastric cancer growth and signal
      transducer and activator of transcription-3 (STAT3) expression. METHODS: We
      assessed the expressions of STAT3, phosphor-STAT3 (pSTAT3), suppressor of
      cytokine signaling-1 (SOCS-1), survivin and Bcl-2 in gastric cancer patients
      after gastrectomy by immunohistochemical method. In addition, in situ
      hybridization was used to further demonstrate the mRNA expression of STAT3 in
      gastric cancer. RESULTS: With the univariate analysis, expressions of STAT3,
      pSTAT3, SOCS-1, survivin and Bcl-2, the size of primary tumor and the lymph node
      metastasis were found to be associated with the overall survival (OS) of gastric
      cancer patients. However, only pSTAT3 expression and the lymph node metastasis
      were identified as the independent factors of OS of gastric cancer with
      multivariate analysis. STAT3 expression was correlated with the lymph node
      metastasis. There were positive correlations between expressions of STAT3,
      survivin, Bcl-2 and pSTAT3 in gastric cancer, whereas there was negative
      correlation between STAT3 expression and SOCS-1 expression in gastric cancer.
      CONCLUSION: STAT3 can transform into pSTAT3 to promote the survival and inhibit
      the apoptosis of gastric cancer cells. SOCS-1 might be the valid molecular
      antagonist to inhibit the STAT3 expression in gastric cancer.

PMID- 21072905
TI  - Modified rendezvous intrahepatic bile duct cannulation technique to pass a PTBD
      catheter in ERCP.
AB  - The rendezvous procedure combines an endoscopic technique with percutaneous
      transhepatic biliary drainage (PTBD). When a selective common bile duct
      cannulation fails, PTBD allows successful drainage and retrograde access for
      subsequent rendezvous techniques. Traditionally, rendezvous procedures such as
      the PTBD-assisted over-the-wire cannulation method, or the parallel cannulation
      technique, may be available when a bile duct cannot be selectively cannulated.
      When selective intrahepatic bile duct (IHD) cannulation fails, this modified
      rendezvous technique may be a feasible alternative. We report the case of a
      modified rendezvous technique, in which the guidewire was retrogradely passed
      into the IHD through the C2 catheter after end-to-end contact between the tips of
      the sphincterotome and the C2 catheter at the ampulla's orifice, in a 39-year-old
      man who had been diagnosed with gallbladder carcinoma with a metastatic right IHD
      obstruction. Clinically this procedure may be a feasible and timesaving
      technique.

PMID- 21072906
TI  - Achalasia combined with esophageal intramural hematoma: case report and
      literature review.
AB  - A 62-year-old male patient was admitted to our hospital due to severe chest pain,
      odynophagia, and hematemesis. Chest computed tomography showed an esophageal
      submucosal tumor. Esophagogastroduodenoscopy (EGD) revealed a longitudinal
      purplish bulging tumor of the esophagus. Endoscopic ultrasound (EUS) showed a
      mixed echoic tumor with partial liquefaction from the submucosal layer. The
      patient was diagnosed with esophageal intramural hematoma as well as achalasia by
      upper gastrointestinal endoscopy, esophagography and esophageal manometry. The
      patient was managed conservatively with intravenous nutrition, and oral feeding
      was discontinued. Follow-up EGD and EUS showed complete recovery of the
      esophageal wall, and finally, the patient underwent endoscopic dilatation for
      achalasia. The patient was symptom free at the time when we wrote this
      manuscript.

PMID- 21072907
TI  - [Ophthalmological profile of patients living with HIV/AIDS].
AB  - INTRODUCTION: Serbia has 2.287 registered HIV positive persons. A certain number
      has ocular complications which are mainly the result of opportunistic infections
      accompanying this illness. Due to a highly stigmatizing environment for people
      living with HIV/AIDS in Serbia, they do not always seek doctors assistance
      despite the fear of losing their sight. CASE REPORT: We presented ophthalmologic
      status of nine HIV positive persons, all at the different phases of the illness.
      The decrease in the visual acuity was the first symptom which led to the
      diagnosis of HIV infection in two of our patients. CONCLUSION: Ophthalmologist
      has an important role in the multidisciplinary approach to patients with HIV/AIDS
      from introducing the diagnosis to the follow-up and the treatment of ocular
      complications which may accompany this chronic illness. With the active
      involvement of eye professionals serious consequences can be prevented, which
      have not only medical but also social and economic implications on the individual
      and the society as a whole.

PMID- 21072908
TI  - [Epidemiology of atrial fibrillation].
AB  - Atrial fibrillation (AF) is the most frequent maintained arrhythmia and
      constitutes a major morbidity cause, especially because of its associated risk of
      ischemic stoke. Additionally, it represents an independent risk factor for global
      mortality. The incidence of AF varies, according to different studies, between a
      minimum of 0.25 per 1000 person/year (women) and 0.9 per 1000 person/year (men)
      and a maximum of 8.9 per 1000 person/year (women) and 11.5 per 1000 person/year
      (men). Several cross sectional and prospective studies indicate that the
      prevalence of AF is inferior to 1% in individuals who are less than 55 years old.
      It is estimated that this arrhythmia's suffers a significant increase throughout
      the entire life span, and that its highest raise occurs between the ages of 65
      and 80. A Portuguese study performe d between June and November 2003, in the
      scope of Rede Medicos-Sentinela, showed an AF prevalence of 0.53% in a population
      of 32,185 Health Centres patients. The mean age of patients suffering from this
      disease is situated within the interval of 70 to 80 years old. It is inferior for
      those who suffer from a concomitant cardiovascular disease, being significantly
      higher for women versus men. The risk factors and comorbidities which are most
      commonly associated to AF are age, several cardiovascular conditions, alcoholism,
      family history of AF and hyperthyroidism. Considering the high rate of stroke
      mortality in Portugal and assuming that AF is present in 15% ischemic stroke
      triggering and that it increases its risk 2 to 7 times, it can be concluded that
      knowledge regarding AF's incidence and prevalence in the different age groups
      will be important in order to improve its level of control, which is essential
      for preventing stroke and better management of this condition's treatment in the
      cardiovascular diseases' general context.

PMID- 21072909
TI  - [Gastroenterology perspectives].

PMID- 21072910
TI  - [Denosumab. The first inhibitor of RANK-ligand for treatment of osteoporosis].
AB  - Denosumab is a fully human monoclonal antibody, that specifically binds with high
      affinity to RANK-ligand (RANKL) and prevents interaction of RANKL with its
      receptor, called RANK (Receptor activator of nuclear factor kappa B). Blocking
      this signalling pathway (RANKL/RANK pathway) inhibits osteoclast differentiation
      and activation, and reduces bone resorption. Application of denosumab (60 mg s.
      c., every six months) results in increased bone mineral density, as showed in
      several clinical trials. Incidence of new vertebral fractures in postmenopausal
      women with osteoporosis was reduced significantly by semi-annual application of
      denosumab versus placebo. Patients suffering from malignant diseases could also
      benefit from treatment with denosumab in future.

PMID- 21072911
TI  - [Vitamin D--an old vitamin in a new perspective].
AB  - Vitamin D, is a secosteroid which, in its active form 1,25-(OH)2-Vitamin D3, has
      hormone activities. Most cells and tissues in the human body have vitamin D
      receptors that stimulate the nuclear transcription of various genes to alter
      cellular function. Vitamin D, appears to have an effect on numerous disease
      states and disorders, including osteoporosis, chronic musculoskeletal pain,
      diabetes (types 1 and 2), multiple sclerosis, cardiovascular disease, and cancers
      of the breast, prostate, and colon. According to many researchers there is
      currently a worldwide vitamin D deficiency in various populations, including
      infants, pregnant and lactating women, and the elderly. The prevalence of vitamin
      D, insufficiency in the general German population is high. Vitamin D in the food
      supply is limited and most often inadequate to prevent deficiencies. Supplemental
      vitamin D is likely necessary to avoid deficiency, especially in winter months.
      The estimated cost saving effect of improving vitamin D status in Germany might
      be up to 37.5 billion euros annually.

PMID- 21072912
TI  - [Minimal bright red rectal bleeding: what should be considered?].
AB  - Blood in faeces or stains of blood on the surface or toilet paper are common
      problems among all age groups. Too few patients seek medical consultation because
      of these symptoms. The differential diagnosis is quite large. Most cases are
      caused by benign anorectal diseases like hemorrhoids. On the other hand
      neoplasias of the anus and intestine or inflammatory bowel disease are important
      diagnoses to be considered. We emphasize that every patient should be seen by a
      doctor and endoscopic investigation should be discussed.

PMID- 21072913
TI  - [Interactions between fluoride and milk?].

PMID- 21072914
TI  - [Atmospheric nitrogen deposition in urban area of Beijing].
AB  - Using ion exchange resin columns method, atmospheric nitrogen deposition was
      observed in the urban area of Beijing from March to September in 2009. The
      average value of atmospheric nitrate nitrogen deposition was 40.59 mg x m(-2) and
      that of atmospheric sulfite nitrogen deposition was 14.66 mg x m(-2) from March
      to June. The average value of atmospheric nitrate nitrogen deposition was 75.13
      mg x m(-2) and that of atmospheric sulfite nitrogen deposition was 20.67 mg x m(
      2) from June to September. Observational results show that atmospheric nitrate
      and sulfite nitrogen deposition had obvious local difference, that is to say,
      there was relatively large amount of deposition around traffic arteries and power
      plants, which shows the character of line/point source of atmospheric nitrate and
      sulfite nitrogen deposition. The average value of atmospheric ammonia nitrogen
      deposition was 12.19 mg x m(-2) from March to June, and 8.46 mg x m(-2) from June
      to September. Observational results show that the change of atmospheric ammonia
      nitrogen deposition among observation points was obvious smaller than atmospheric
      nitrate and sulfite nitrogen deposition, which shows the character of non-point
      source of atmospheric ammonia nitrogen deposition.

PMID- 21072915
TI  - [Size distributions of organic carbon (OC) and elemental carbon (EC) in Shanghai
      atmospheric particles].
AB  - Size distributions of organic carbon (OC), elemental carbon (EC) and secondary
      organic carbon (SOC) in atmospheric particles with size range from < 0.49, 0.49
      0.95, 0.95-1.50, 1.50-3.00, 3.00-7.20, > 7.20 microm, collected in Jiading
      District, Shanghai were determined. For estimating size distribution of SOC in
      these atmospheric particles, a method of determining (OC/EC)(pri) in atmospheric
      particles with different sizes was discussed and developed, with which SOC was
      estimated. According to the correlation between OC and EC, main sources of the
      particles were also estimated roughly. The size distributions of OC and SOC
      showed a bi-modal with peaks in the particles with size of < 0.49 microm and >
      3.0 microm, respectively. EC showed both of a bi-modal and tri-modal. Compared
      with OC, EC was preferably enriched in particles with size of < 0.49 microm. Mass
      concentrations of OC and EC in fine particles (< 3.00 microm) accounted for 59.8%
      80.0% and 58.1%-82.4% of those in total suspended particles. OC and EC were
      preferably enriched in fine particles (< 3.00 microm). The concentrations of SOC
      in the particles with different sizes accounted for 15.7%-79.1% of OC in the
      particles with corresponding size. Concentrations of SOC in fine aerosols (< 3.00
      microm) and coarse aerosols (> 3.00 microm) accounted for 41.4% and 43.5% of
      corresponding OC. Size distributions of OC, EC and SOC showed time-dependence.
      The correlation between OC and EC showed that the main contribution to
      atmospheric particles in Jiading District derived from light petrol vehicles
      exhaust.

PMID- 21072916
TI  - [Geochemical character of precipitation in summer of Shanghai 2008-2009].
AB  - The chemical compositions of the rainwater collected in Shanghai in Summer of
      2008-2009 were investigated. The chemical character and pollutant source of
      rainwater were evaluated depended on HYSPLIT model, ions tracer techniques,
      correlation and principal component analysis. The results showed that: (1) the
      mean pH in rain was 4.72 and 4.68; (2) the frequency of acid rain was 53.30% and
      63.30%, respectively, in 2008 and 2009; (3) ionic concentration was SO4(2-) >
      NH4+ > NO3- > Cl- > Ca2+ > Na+ > Mg2+ > K+, in which the secondary components
      like SO4(2-), NO3- and NH4+ contributed significantly to total ions of rainwater
      and they accounted for 55.01% and 65.97% of total ions in 2008 and 2009,
      respectively, which indicate the severe secondary pollution in Shanghai; (4) the
      ratio of SO4(2-) to NO3- in Summer precipitation in 2008 and 2009 was 3.19 and
      2.13, respectively, which implies sulfuric-nitrous mixed type of precipitation;
      (5) the content of DOC varied from 1.36 mg/L to 10.69 mg/L and average value was
      2.44 mg/L in rainwater; (6) SO4(2-) and NO3- were mainly in the form of (NH4)
      2SO4 and NH4NO3, which showed the dominant neutralization effect of NH4+ over
      Ca2+ in Summer. Source identification indicated that SO4(2-), NH4+, NO3-, K+ and
      most Ca2+ derived from anthropogenic sources, while Mg2+ and Cl- derived from
      both marine and non-marine but non-marine was over marine. The chemistry of
      precipitation in Shanghai was impacted by local pollutants and the long-and
      moderate-range transport by Southwest monsoon according to backward trajectory
      analysis.

PMID- 21072917
TI  - [Influence of inorganic additives on the distribution of polycyclic aromatic
      hydrocarbons in the smoke and ash from mosquito coils burning].
AB  - The influence of inorganic additives (NaCl, Na2CO3 and CaCO3) on the distribution
      of polycyclic aromatic hydrocarbons (PAHs) in the smoke and ash from mosquito
      coils burning was studied, GC-MS technique was applied to analyze the contents of
      16 priority-controlled PAHs recommended by US EPA. The results show that 16
      priority-controlled PAHs are detected in the smoke of mosquito coil without
      additives, characterized by the predominance of 2- to 3-ring PAHs, which are
      ranked as NaP (3.109 microg x g(-1)) > Phe (1.230 microg x g(-1)) > AcP (0.495
      microg x g(-1)) > FluA (0.311 microg x g(-1)); the emission factors in the ash
      are also predominated by 2- to 3-ring PAHs, but the total PAHs emission factors
      in the ash are only 4.7% of those in the smoke. NaCl and Na2CO3 additives can not
      decrease the emission of PAHs but promote total emission factors and TEQ of PAHs
      in the smoke of mosquito coils increase remarkably. The best additive in this
      study is CaCO3. With the increase of the addition of CaCO3, the proportion for 2-
      to 3-ring PAHs in the smoke increases remarkably than that in the ash, while the
      status reverse for 5- to 6-ring PAHs. CaCO3 with mole fraction of 2.0% has the
      most excellent property to decrease total emission factors and TEQ of PAHs in the
      smoke of mosquito coils, and the total emission factors and TEQ of PAHs decrease
      1.8% and 86.6% respectively compared with the control.

PMID- 21072918
TI  - [Monitoring of organic pollutants in river based on polarimetric SAR].
AB  - The rivers with the distinct gradient of water quality in the southern region of
      China were selected as a case study. The objective of this study was to develop
      the monitoring and evaluating technology of the water quality based on C-band
      polarimetric synthetic aperture radar (POLSAR). The random rough surface
      scattering model to describe the electromagnetic scattering characteristics of
      polluted water was briefly introduced. The potential effect of organic pollutants
      to the scattering model and backscattering coefficient were explored. The
      simultaneously obtained POLSAR data and the measured water quality indexes were
      analyzed. By comparing the POLSAR data and the water quality indexes, it could be
      observed that the chemical oxygen demand (COD) was in proportional to the ratio
      between HH and VV backscattering coefficients, which matched the analysis based
      on electromagnetic scattering theory. A fitting model was proposed to retrieve
      the chemical oxygen demand by ratio between HH and VV channel backscattering
      coefficients using least square method, with the fit coefficient of 0.90. In this
      study, the model using the ratio between HH and VV backscattering coefficients
      was established, which was mainly based on the analysis of experimental results,
      and was also supported by theoretical interpretation.

PMID- 21072919
TI  - [Local sensitivity and its stationarity analysis for urban rainfall runoff
      modelling].
AB  - Sensitivity analysis of urban-runoff simulation is a crucial procedure for
      parameter identification and uncertainty analysis. Local sensitivity analysis
      using Morris screening method was carried out for urban rainfall runoff modelling
      based on Storm Water Management Model (SWMM). The results showed that Area, %
      Imperv and Dstore-Imperv are the most sensitive parameters for both total runoff
      volume and peak flow. Concerning total runoff volume, the sensitive indices of
      Area, % Imperv and Dstore-Imperv were 0.46-1.0, 0.61-1.0, -0.050(-) - 5.9,
      respectively; while with respect to peak runoff, they were 0.48-0.89, 0.59-0.83,
      0(-) -9.6, respectively. In comparison, the most sensitive indices (Morris) for
      all parameters with regard to total runoff volume and peak flow appeared in the
      rainfall event with least rainfall; and less sensitive indices happened in the
      rainfall events with heavier rainfall. Furthermore, there is considerable
      variability in sensitive indices for each rainfall event. % Zero-Imperv's
      coefficient variations have the largest values among all parameters for total
      runoff volume and peak flow, namely 221.24% and 228.10%. On the contrary, the
      coefficient variations of conductivity among all parameters for both total runoff
      volume and peak flow are the smallest, namely 0.

PMID- 21072920
TI  - [Impacts on nutrient export by landscape heterogeneity based on sub-watershed].
AB  - Landscape features of a watershed are important factors affecting non-point
      source (NPS) pollution. Sub-watershed bounds were delineated and landscape
      heterogeneity was analyzed based on GIS and RS in Xitiaoxi watershed which
      located the upper reach of Taihu Lake area. Nutrient export intensity of sub
      watersheds was estimated by revised export coefficient model. Then the
      relationships between nutrient export and main landscape types, as well as
      Shannon diversity index (SHDI) in sub-watershed units were analyzed. Results
      show, TN and TP export intensity have obvious spatial difference, which changed
      from 3.01 kg/(hm2 x a) to 15.44 kg/(hm2 x a) and 0.049 kg/(hm2 x a) to 0.355
      kg/(hm2 x a) respectively. The dominated landscape types including cultivated
      land and forest land quantitatively related with nutrient export intensity. TN
      and TP export intensity will decrease 0.203 1 kg/(hm2 x a) and 0.0152 kg/(hm2 x
      a) respectively with 10% increased of forest area, and will increase 0.5726
      kg/(hm2 x a) and 0.0273 kg/(hm2 x a) with 10% increased of cultivated land area.
      The relationship between nutrient export intensity and SHDI exhibited second
      degree polynomial, export intensity increased by SHDI increasing and to maximum
      when SHDI equals 1.5, then decreased with SHDI increasing. This research results
      will provide an important reference value for NPS management.

PMID- 21072921
TI  - [Characteristics of temporal and spatial distribution of water quality in urban
      wetland of the Xixi National Wetland Park, China].
AB  - As the first national wetland park and the representatively urban wetland, Xixi
      wetland must provide the services of tourism and recreation especially. Based on
      the data which had been collected monthly from March to August in 2009, the
      objectives of this paper were to describe the characteristics of water quality in
      temporally and spatially. The results indicated that: (1) the characteristics of
      water quality in spatially are significantly corrected with the function of
      wetland. Total nitrogen (TN) and total phosphorus (TP) average concentrations are
      0.78 mg/L and 0.07 mg/L respectively in natural ponds, while the concentrations
      of TN and TP in ornamental ponds are 1.37 mg/L and 0.17 mg/L respectively. The
      concentrations of TN and TP are 2.91 mg/L and 0.18 mg/L in natural streams and
      1.91 mg/L and 0.09 mg/L in sight-seeing streams; (2) the nutrition in Xixi
      wetland is different in temporally. The nutrition in Xixi is at the level of
      moderate eutrophication, while the nutrition is higher in summer than it in
      spring; (3) the level of eutrophication in pounds is lower than it in streams, of
      which the level of eutrophication in natural ponds is lower than it in ornamental
      ponds and the level of eutrophication in natural streams is higher than it in
      sight-seeing streams by contraries. In order to improve water quality in Xixi
      wetland, the valid measure is to strengthen the management of ornamental ponds
      and natural streams.

PMID- 21072922
TI  - [Research on iron in marshy rivers of the Sanjiang Plain].
AB  - River waters (including the main river and marshy river) were sampled to study
      the iron concentration, species and complexed competitive ability in the Sanjiang
      Plain in order to reveal the influence of wetland reclamation on the iron species
      and output flux. The cross-flow filtration technique was employed to separate
      iron species according to size fraction. The result showed that the typical
      marshy river which is rich in organic matters became an important iron source for
      atypical marshy river. In the typical marshy river, the concentration of total
      dissolved and acid-labile iron reached to 1.16 and 0.81 mg x L(-1), respectively.
      Complexed (accounting 70.9% of total dissolved iron) and ion iron (accounting
      9.3% of total dissolved iron) were the primary species in dissolved iron.
      Therefore, iron transported primarily as low-molecular-weight iron forms in river
      waters in the Sanjiang Plain. The low-molecular-weight iron accounted for 68.7%
      and 82.2% of total dissolved iron and low-molecular-weight iron concentrations
      reached to 0.13 and 0.88 mg x L(-1) in the main and typical marshy river,
      respectively. The ferric iron concentration in the typical marshy river was 3.1
      times higher than that in the atypical marshy river. Little difference of ferrous
      iron contents between the typical and atypical marshy river was observed. Fe(II)
      was found in complexed and colloidal iron through ligand competitive experiment.
      In the typical marshy river, complexed iron had a higher ligand competitive
      ability, which could form more stable complexed iron. The decline of the stable
      complexed iron output flux due to reclamation of the Sanjiang wetland would
      greatly influence the distance of iron transportation, especially iron output to
      the coastal waters.

PMID- 21072923
TI  - [Experimental research on migration characteristics of nitrogen and phosphorus in
      Qingtongxia irrigation district].
AB  - Taking the Qingtongxia irrigation district at the Yellow River upstream as an
      example, based on the monitor experiment material, this paper has analyzed the
      migration characteristics of nitrogen and phosphorus in the water conveyance
      system, the field system and the drainage system in the irrigations district. The
      results showed that, the concentrations of nitrogen and phosphorus showed
      increasing tendency in the water conveyance system and the increasing extent
      related to the channel substrate and content of nitrogen and phosphorus. In the
      field system, the fertilizer application process has a great influence on the
      concentration of nitrogen and phosphorus in farmland irrigation drainage and
      soil. During the crop growing period, nitrogen content in the soil above 60 cm
      changes greatly, total phosphorus content in the soil changes slightly
      correspondingly. In the drainage system, the concentrations of nitrogen and
      phosphorus showed decreasing tendency, from the end of farm ditch to outlet of
      agricultural drain, the concentration of ammonia nitrogen, nitrate nitrogen and
      total phosphorus in the agricultural drain decreased by 25%, 41% and 45%
      respectively. Affected by livestock and poultry breeding pollution and so on, the
      concentration of nitrogen showed increasing tendency in mainstay drainage ditch.

PMID- 21072924
TI  - [Seasonal variation characteristics of algae biomass in Chaohu Lake].
AB  - The biomass and distribution of algae community in Chaohu Lake were investigated
      in 2008. At the same time, the seasonal variations of algae translocation between
      the sediment and overlying water were also quantitative studied by self-made
      "algae up/down trap". Chaohu Lake was dominated by Cyanobacteria all the year,
      and dominant Cyanobacteria species changed in different seasons. In spring,
      Anabaena was the dominant species, and Microcystis was the subdominant species;
      In the whole summer and autumn, the dominant species is Microcystis. Algae
      biomass increased significantly from May and the maximum appeared in August, was
      146.37 mg x m(-3) with Chl-a. The value of algae biomass were 9.75-16.24 mg x kg(
      1) in the surface sediments, and the minimum appeared in Summer, then the algae
      biomass increased gradually with the maximum value in winter. Translocation
      process between the sediment and the overlying water occurred throughout the
      study period. The recruitment rates increased at first with the maximum rates in
      early August, was 0.036 8 mg x (m2 x d) (-1), and then had a downward tendency.
      However the sedimentation rates increased slowly firstly with the maximum rate in
      early September, then it decreased sharply, was 0.032 1 mg x (m2 x d)(-1).
      Multiple stepwise regression showed that temperature was the most significant
      factor for the algae biomass in Chaohu Lake, Total nitrogen (TN) and Total
      phosphorus(TP) are sub-important factors.

PMID- 21072925
TI  - [Chemicohydrographic characteristics and the seasonal variations of nutrients at
      35 degrees N transect in the cold water mass of the Southern Yellow Sea].
AB  - Based on the four cruises during 2006-2007, the chemicohydrographic
      characteristics and the seasonal variations of nutrients at 35 degrees N transect
      in the cold water mass of the Southern Yellow Sea were analyzed. The results
      showed that: In Winter, hydrological conditions in the eastern part of the
      section was significantly influenced by the Yellow Sea Warm Current, and the
      vertical mixing in the deep water had not reached the bottom, which led to the
      different distribution of the elements in the eastern and western part of the
      section, the vertically uniform distribution was presented in the west and the
      upper water of the east, while the stratification structure was found in the
      bottom water of the east. In Spring, the Yellow Sea warm current residual water
      and the Qingdao cold water mass were the most obviously hydrological
      characteristics, and because of the increasing of the temperature in the upper
      water and the weakening of the vertical mixing, the stability of the water column
      increased gradually; compared with winter, the contour trend of DO, pH and
      nutrients in deep water transferred to the more horizontal direction, and with
      the arrival of spring blooming, the nutrient concentrations in the upper water
      decreased significantly, besides, the subsurface chlorophyll maximum (SCM)
      phenomena also began to emerge. In Summer, the section was influenced by the
      thermocline and the Yellow Sea cold water mass, which was accompanied with the
      maximum value phenomenon of DO and pH, in addition, the nutrient concentrations
      were low in upper water and high in bottom water, and compared with spring, the
      further reduction of the nutrient concentrations existed in upper water, but the
      nutrient concentrations were increasing dominantly in the water below the
      thermocline. In Autumn, with the decreasing of the temperature in the upper water
      and the enhancing of the vertical mixing, the stability of the water column
      decreased, but the vertical mixing in the deep water was still not smooth, and
      the nutrient concentrations in the bottom water of the east were higher than
      those in summer. This study further revealed the influencing mechanism of the
      mixing, stratification as well as other physical processes on the vertical
      distribution and its seasonal variations of the elements.

PMID- 21072926
TI  - [Degradation of dimethyl phthalate (DMP) in aqueous solution by UV/Si
      FeOOH/H2O2].
AB  - In this study the new catalyst Si-FeOOH was synthesized by adding Si to the
      traditional FeOOH and the mechanic strength of this new catalyst could be
      enhanced greatly. The photo-degradation of dimethyl phthalate (DMP) by UV/Si
      FeOOH/H2O2 was investigated. The new catalyst Si-FeOOH was amorphous structure
      with high surface area and low soluble iron by XRD, IR and SEM. The efficiency of
      DMP degradation by UV/Si-FeOOH/H2O2 could reach 97% after 30 min reaction time at
      pH 5, 0.5 g/L dosage of Si-FeOOH, and 2.0 mmol/L of H2O2 under 125W UV365
      irradiation. DMP could be degraded effectively by synergistic effect of UV, Si
      FeOOH and H2O2. The Si-FeOOH photocatalyst can be very easily recovered and its
      catalytic activity also remained after several rounds of reaction.

PMID- 21072927
TI  - [Oxidative efficiency of the system of electrolysis coupled ozonation].
AB  - The oxidation system of electrolysis coupled ozonation (electrolysis-ozonation)
      was used to degrade 4-chlorophenol (4-CP), and its mechanism was discussed on the
      basis of kinetic analysis. The experimental results indicated the electrolysis
      ozonation system had a significant synergistic effect during degradation of 4-CP.
      For example, the electrolysis-ozonation had the 4-CP removal rate of 92.7% and
      the COD removal rate of 64.9% in 900 s, respectively; while electrolysis alone
      plus ozonation alone only had the 4-CP removal rate of 69.7% and the COD removal
      rate of 30.1% under the same conditions. The results of H2O2 concentration
      analysis and photocurrent test showed that the synergistic mechanism of
      electrolysis-ozonation included two factors: (1) production of *03- at the
      cathode; (2) H2O2 generation resulting from reduction of dissolved oxygen. The
      above two factors led to generation of *OH in system effectively.

PMID- 21072928
TI  - [Kinetics of humic substances oxidation degradation by Fenton's reagent].
AB  - Humic substances (HS) oxidation degradation by Fenton's reagent was kinetically
      investigated in this study. HS was removed by both oxidation and coagulation
      during Fenton treatment. Moreover, initial pH, the dosage of Fenton's reagent and
      initial concentration of HS had a significant impact on HS oxidation rate and the
      oxidation mainly occurred at the first 60 min of reaction time. The empirical
      kinetic equation for HS oxidation by Fenton's reagent under the conditions of 308
      K of temperature, 4.0 of pH, 5-40 mmol x L(-1) of Fe2+, 40-120 mmol x L(-1) of
      H2O2, 250-1 000 mg x L(-1) of HS, could be described using a kinetic model, which
      was fitted very well with the experimental data. The overall reaction order is
      2.34. The lower activation energy of 14.9 kJ x mol(-1) shows that Fenton reaction
      can be initiated easily. The reaction order of H2O2 (0.86) is higher than that of
      Fe2+ (0.47), which indicates that the effect of initial H2O2 concentration is
      greater than that of Fe2+ on the oxidation degradation of HS by Fenton process.

PMID- 21072929
TI  - [Research in high frequency ultrasonic for degradation of azo dye wastewater
      containing MX-5B].
AB  - The degradation of azo dye wastewater, containing MX-5B, was investigated by
      using high frequency ultrasonic irradiation. The effect of different factors like
      the initial pH of solution, sonolysis parameters, air-blowing, Fe2+ concentration
      were studied, the synergistic action of complex frequency and the mechanism of
      degradation was explored primarily. The results show that MX-5B in aqueous
      solution can be degraded efficiently by ultrasonic irradiation, when the pH 3.5,
      ultrasonic frequency 418.3 kHz, ultrasonic power 69 W, color removal rate up to
      100% in 180 min. Adding of Fe2+ and blowing air had some effects. The results
      also indicated that radical-oxidation controlled the ultrasonic decompose of MX
      5B and MX-5B ultrasonic removal was observed to behave as pseudo-first-order
      kinetics under different experimental conditions tested in the present work.
      Comparison of UV-Vis absorption spectrums before and after treatment showed that
      all of the conjugate structure and part of aromatic structure were destroyed
      after being ultrasonic irradiation.

PMID- 21072930
TI  - [Research on removal of copper, manganese and zinc ions using cation exchange
      membrane based on Donnan dialysis].
AB  - Based on Donnan dialysis technique, the mechanism that influences the exchange
      capacity of the membrane and the interaction mechanism between two co-existing
      ions are investigated in this paper, where the cation exchange membrane is
      applied to remove the heavy metal ions such as copper, manganese, zinc. The
      following results were obtained: It is applicable to use the cation exchange
      membrane to remove copper, manganese and zinc ions and 75%-85% of removal
      efficiency can be obtained; when the concentration and charge number are the
      same, the smaller the radius of hydrated heavy metal, the quicker the ion diffuse
      and consequently the higher removal efficiency the membrane can achieve, which is
      the main factor; when the radius of the hydrated heavy metals are approximately
      same, the membrane will have higher removal efficiency to the ion with lower
      atomic number; when the ions with same charge number and concentration co-exist,
      both of them are removed but with different removal speeds for existing of
      disturbance between them and there exist diffusion competition, i.e. those who
      are more prone to be exchanged will be more competitive and more likely to low
      the removal rate of the other ion seriously; if the total concentration of the
      ions is far lower than the exchange capacity of the membrane, the removal
      efficiency when the ions coexist is not lower too much than that of the case when
      they exist lonely.

PMID- 21072931
TI  - [Effect of nitrite accumulation on enhanced biological phosphorus removal (EBPR)
      in A2O process treating domestic wastewater].
AB  - At normal temperature, short-cut nitrification and denitrification was achieved
      in a lab-scale A2O process treating low C/N ratio domestic wastewater by
      controlling DO concentration of 0.3-0.5 mg/L and increasing the internal reflux
      ratio to decrease the actual aerobic HRT. However, the phosphorus removal in A2O
      process was deteriorated with the increasing of the nitrite concentration in the
      effluent. The factors causing phosphorus removal deterioration, such as the
      influent COD concentrations, temperature, pH and free nitrous acid (FNA) were
      systematically analyzed. Experimental results showed that the nitrite
      accumulation resulting from short-cut nitrification affected anaerobic P release
      and aerobic P uptake. Especially, the higher FNA concentration (HNO2-N 0.002
      0.003 mg/L) in the aerobic zone significantly inhibited the aerobic P uptake,
      which was the major reason causing P removal deterioration. Through adding the
      carbon sources in influent to enhance anaerobic P release and denitrification,
      the nitrite and FNA concentrations in the aerobic zone were decreased, and the P
      removal was recovered. More than 96% of PO4(3-) -P could be removed in A2O
      process.

PMID- 21072932
TI  - [Enhanced biological phosphorus removal in single aerobic process].
AB  - When SBR with sodium acetate as the sole carbon source and operated under
      alternative anaerobic and aerobic condition had achieved a good performance in
      phosphate removal, it was shifted to completely aerobic treatment system, and
      found that a good phosphorus removal with removal efficiency of the highest of
      73.9%, the lowest of 40% and an average of about 50% was still achieved. The
      phosphate removal could last 80 cycles before regeneration. Phosphate content of
      sludge in the SBR increased from 1.43% to 6.56%. PHB and glycogen in the sludge
      were 27 mg/g and 26 mg/g, respectively. Both of them in the sludge during the
      whole cycle were of slight variation. Based on analysis of carbon consumption and
      phosphate absorption as well as their relationship, it is considered that this
      enhanced biological phosphorus removal in single aerobic process is due to that,
      the sludge in the system can use ATP released from aerobic oxidation of sodium
      acetate after acclimation to condition of sodium acetate as the sole carbon to
      synthesize poly-P granule in cell to a certain content.

PMID- 21072933
TI  - [Cultivation of aerobic granules in a large pilot SBR with domestic sewage].
AB  - The cultivation of aerobic granules in a large pilot-scale SBR was investigated
      using domestic wastewater. After operation of 210 days, the granules with a
      diameter of 330 microm were successfully formed by seeding anaerobic digested
      sludge. Results showed that, during the first three months of operation under low
      organic load of influent, removal efficiencies of pollutants increased steadily
      including COD, NH(4+)-N, total nitrogen (TN) and total phosphorous (TP).
      Meanwhile, microorganisms related to nitrogen and phosphorous were enriched. The
      organic load was enhanced since cycle time was shortened to 6 h, and the
      operational performance of the reactor still remained stable. Moreover, the
      average particle size of the sludge started to increase, along with excellent
      settling ability and high bioactivity. After the formation of aerobic granules,
      Sludge volume index (SVI) was maintained at 30 mL x g(-1) and the mixed liquor
      suspended solid (MLSS) concentration in the SBR reached 8.8 g x L(-1). MLVSS/MLSS
      ratio of the sludge increased to 82% with a high oxygen uptake rate (OUR) of 5.32
      mg x (min x L)(-1). Bacillus was dominant on the outer layer of granules, while
      cocci were mainly located inside. The average COD and TP removal efficiencies
      kept at 90% and NH(4+) -N was almost completely depleted, NO(3-) -N and NO(2-) -N
      were not accumulated in the effluent. The aerobic granules were also capable of
      achieving simultaneous nitrification and denitrification (SND) in a single SBR
      cycle, which resulted in a high TN removal efficiency of 80%.

PMID- 21072934
TI  - [Sewage sludge conditioning by bioleaching-dual PAC and PAM addition].
AB  - Bioleaching-dual polyaluminum chloride (PAC) and polyacrylamide (PAM) addition
      was used to condition sewage sludge. The results showed that FeSO4 x 7H2O
      addition improved the bioleaching rate obviously with a fixed sulfur power dosage
      of 3 g x L(-1); when the FeSO4 x 7H2O dosage was 8 g x L(-1), the bioleaching
      lasted 1.5 d to decrease the sludge pH below 2. Bioleaching improved the sludge
      dewaterability significantly with a specific resistance to filtration (SRF)
      reduction of 77.52% from 6.45 x 10(10)s2 x g(-10 to 1.45 x 10(10)s2 x g(-1), but
      the bioleached sludge was still difficult to be dewatered. After adjusting the
      bioleached sludge pH to 6, PAC and PAM were used to enhance conditioning of the
      bioleached sludge. The results indicated that the optimal dosage was 200 mg x L(
      1) for PAC or 50 mg x L(-1) for PAM when single chemical was used. When PAC and
      PAM were dually used, the optimal dosages of PAC and PAM were 100 mg x L(-1) and
      25 mg x L(-1), respectively; SRF and moisture of sludge cake reduced to 2.02 x
      10(8) s2 x g(-1) and 74.81%, respectively, showing good dewaterability of the
      treated sludge. Compared with the single use of PAC and PAM, the dual use of PAC
      and PAM showed the advantages of lower cost and better conditioning effect.

PMID- 21072935
TI  - [Preparation and characterization of activated carbon-silver composite with
      antibacterial behavior via NaBH4 reduction method].
AB  - Activated carbon-silver composite (Ag/AC) for antibacterial behavior with
      capability of controlling silver release was prepared by NaBH4 reduction method.
      The antibacterial activity towards E. coil and resistance of water erosion was
      investigated through a point of view of water purification. N2 adsorption
      isotherm, Scanning electron spectroscopy (SEM)-Energy dispersive X-ray
      spectrometer(EDS) and X-ray diffraction(XRD) was used to characterize the surface
      morphology and pore properties. As an experiment result, silver was deposited on
      AC in the state of Ag0. The content of silver supported, specific surface area,
      nucleus formation and growth mechanism, particle size and distribution of the
      generated silver particles were determined by the concentration of the aqueous
      solution of AgNO3. With the increasing of AgNO3 solution concentration, the
      activity of the obtained Ag/AC changed from non-active to inhibitory and then to
      high antibacterial. Ag/AC supported silver content of 2.70% killed all the
      concentration of 2 x 10(6) CFU/mL of E. coil. However, it showed high resistance
      to water erosion that silver loss was 21.1% in 600 h for surging. High
      antibacterial activity and control silver release can be simultaneously realized
      by the NaBH4 reduction method.

PMID- 21072936
TI  - [Surface properties and adsorption characteristics for fluoride of goethite,
      kaolinite and their association].
AB  - The basic properties of goethite, kaolinite and their association were
      characterized using X-ray diffraction (XRD) , scanning electron microscopes
      (SEM), Fourier transform infrared spectroscopy (FT-IR), potentiometric
      titrations, specific surface area (SSA) and micropore analysis. Moreover, the
      adsorption capacity and adsorption models of fluoride by the investigated samples
      were studied. Results show that when kaolinite and goethite presented
      simultaneously in the same suspension system, goethite was apt to coat the
      surface of kaolinite and the interactions between them could occur rapidly. As a
      result, the binary association containing kaolinite and goethite was formed. The
      binary association possessed the pore diameter of 0.42 nm and 0.61 nm, specific
      surface area of 34.08 m2/g, surface fractal dimension of D = 2.726 and the
      pH(PZNPC) (pH of point of zero net proton charge) in the range of 5.50-6.50. At
      the initial pH 6. 00, the maximum adsorption capacity (q(max) of goethite,
      kaolinite and association was 4.506, 0.608 and 3.520 mg/g respectively. The
      adsorption of fluoride by the single kaolinite or goethite could be attributed to
      monolayer adsorption and the data of isotherm adsorption could be well fitted by
      Langmuir model (R2 = 0.991 and R2 = 0.964 respectively). The Freundlich model was
      suitable for describing the adsorption of fluoride by the binary association (R2
      = 0.995), which indicated that the surface of the binary association is
      heterogeneous and is probably provided with multilayer adsorption sites. The
      adsorption mechanisms for fluoride by the investigated samples include anion
      ligand exchange, surface coordination and electrostatic attraction. In addition,
      F acting as a bond bridge between the surfaces of kaolinite and goethite
      contributed to the adsorption of fluoride too. Compared to the single goethite or
      kaolinite, the binary association exhibited the higher specific surface area,
      surface fractal dimension and adsorption capacity for fluoride as well as the
      lower amount of hydroxyls and net proton charges on it's surface, although no
      significant variation was found in the porosity structure of the association.

PMID- 21072937
TI  - [Biodegradation and adsorption of bio-zeolite on pyridine and quinoline].
AB  - The study was to explore the treatment of pyridine, quinoline and their
      transformation product, NH(4+) -N, by the biodegradation and adsorption of a
      natural and a modified bio-zeolites. The experiment results demonstrated that the
      mixed bacteria on the bio-zeolites, a pyridine-degrading bacterium and a
      quinoline-degrading bacterium, could degrade pyridine and quinoline
      simultaneously. The NH(4+) -N transformed from pyridine and quinoline could be
      adsorbed by the natural and modified zeolites. The adsorption capacity of the
      modified zeolite was lower than that of the natural zeolite. However, more
      microorganisms could attach on the surface of the modified zeolite, so the
      application of the modified bio-zeolite has a better prospect in actual treatment
      of pyridine and/ or quinoline pollution.

PMID- 21072938
TI  - [Electricity generation and quinoline degradation of pure strains and mixed
      strains in the microbial fuel cell].
AB  - Microbial flora composition of microbial fuel cells (MFC) is important to the
      electricity generation. Four bacterium strains Q1, b, c and d which represent all
      different morphology of culturable bacterium were isolated from a MFC using 200
      mg x L(-1) quinoline as the fuel and operating for at least 210 days. Strains Q1,
      c and d were Pseudomonas sp. based on 16S rDNA sequence analysis, while strain b
      was Burkholderia sp. Double-chamber MFCs using 200 mg x L(-1) quinoline and 300
      mg x L(-1) glucose as the fuel and potassium ferricyanide as the electron
      acceptor were constructed. Results showed that strain b, c and d were non
      electrogenesis. The electrical charges of MFC inoculated electrogenesis strain Q1
      with non-electrogenesis strain b, c and d respectively were 3.00, 3.57 and 5.13C,
      and the columbic efficiency were 3.85%, 4.59% and 6.58%, which were all lower
      than that inoculated with pure Q1, because of the interspecific competition of
      electrogenesis and non-electrogenesis bacteria. Combinations of Q1 with the other
      three strains respectively resulted in 100% of quinoline degradation rates within
      24h, which is better than pure cultures, that is, mixed microbial populations
      perform better in MFC when complex organics are used as the fuel. GC/MS analyses
      showed that only 2(1H)-quinolinone and phenol existed in the effluent of the MFC,
      which was inoculated with only Q1 or mixed bacteria.

PMID- 21072939
TI  - [Primary study on contents of sulfate reducing bacteria (SRB) and organic matter
      from intertidal zone at Chongming Dongtan].
AB  - Collected soil samples from different tidal flats and elevation in Chongming
      Dongtan wetland, then conducted sulfate-reducing bacteria (SRB) based on MPN
      method, determined organic matter content and calculated SO4(2-)/Cl- molar ratio,
      for the research on the distribution of SRB, relevance to soil organic matter
      content as well as influence of plant rhizosphere environment on SRB growth. The
      results show the distribution of SRB is ranked as middle flat > climax flat >
      bald flat. The same tidal flats at different depths, the SRB levels are shown as
      51-52 cm > 21-22 cm > 81-82 cm, therefore 51-52 cm soil depth of Dongtan wetland
      is the suitable area for SRB to grow. However, in different tidal and depth, the
      distribution of organic matter content presents climax flat > middle flat > bald
      flat. From 21-51 cm, as the depth increasing, the organic matter content
      decreases while the amount of SRB significantly increasing, which indicates SRB
      utilizes the soil organic matter to carry out reduction reaction. The SO4(2-)/Cl-
      molar ratios of all soil samples are less than 0.05, indicating that SRB are
      actively engaged in sulfate reduction. The concentration of SRB in reed
      rhizosphere soil is the highest, showing that Phragmites australis rhizosphere
      environment in Dongtan wetland could enhance SRB growth, while the number of SRB
      in Spartina alterniflora rhizosphere environment is relatively lower than the non
      rhizosphere environment, indicating that the rhizosphere effect has different
      effects on SRB in Dongtan tidal flats.

PMID- 21072940
TI  - [Distribution and diversity of sulfate-reducing bacteria in a crude oil gathering
      and transferring system].
AB  - The distribution of sulfureted hydrogen (H2S) as well as sulfate-reducing
      bacteria (SRB) distribution and diversity in crude oil and oilfield production
      water samples from a oil gathering and transferring system in Changqing Oilfield
      of China were investigated by methylene blue colorimetric method, the most
      probable number technique and sequence analysis of the 16S rRNA gene,
      respectively. At the oil gathering and transferring system which from oil well
      through oil flowstation and then to oil comprehensive treatment station, the
      results showed that in oil samples, the content of H2S were 105.80, 99.70, and
      24.57 mg x L(-1), respectively; and the count of SRB were 98, 300, and 680 CFU
      x100 mL(-1), respectively. In water samples, the content of H2S were 1.13, 2.80,
      and 3.49 mg x L(-1), respectively; and the count of SRB were 9 500, 40 000, and
      76 000 CFU x 100 mL(-1), respectively. The abundance of SRB in the water samples
      is about 100 times than that in the crude-oil samples. High concentration of H2S
      in oil well inhibited the growth of SRB, thereby the count of SRB in oil well
      were small. With the reduction of H2S concentration, the actions of inhibition
      weakened and disappeared, then the number of SRB were gradual increase in the
      gathering and transferring system. For the initial concentration of H2S in water
      samples was low, and the number of SRB were large, then the content of H2S
      increased gradually with the number of SRB were increased. Sequence analysis of
      the 16S rRNA gene indicated that SRB related to Desulfovibrionaceae sp. and
      Desulfococcus sp. were detected in the water and crude oil samples,
      simultaneously. However, SRB related to Desulfomonile sp., Desulfotomaculum sp.
      and Desulfosarcina sp. were detected in the water samples but not in crude-oil
      samples. Abundance of SRB was increased due to the variation of environmental
      condition during the period of oil gathering and transferring process.

PMID- 21072941
TI  - [Isolation and characterazation of a carbazole-degrading bacterial strain].
AB  - A bacterial strain was isolated from soil samples using plate screening
      techniques. Results indicated this isolated were able to use carbazole as sole
      source of carbon and energy, simultaneously, including N-Methylcarbazole, 4
      Hydroxycarbazole and 2,2'-Biphenol. It was identified as Flavobacterium sp.
      according to its morphology, and biochemical properties, and 16S rDNA sequence
      analysis. Utilization of carbazole by the isolates was confirmed by the increase
      in bacterial biomass and the decrease in substrate concentration in liquid
      cultures. The optimal pH and temperature for cell growth and carbazole
      degradation were 7.5 and 30 degrees C, respectively. Resting cells grown in Luria
      broth also showed activity for decomposing other heterocyclic compounds. In
      addition, biodegradation of carbazole was carried out with carbazole degrading
      strain KH-6. The results indicated that 90% of the carbazole could be degraded in
      the sterilized soil. And strain KH-6 could enhance the degradations of carbazole
      significantly.

PMID- 21072942
TI  - [Production of biodemulsifier by Alcaligenes sp. S-XJ-1 using waste diesel oil].
AB  - Biodemulsifier is a new type of demulsifiers for breaking oil-water emulsion. One
      demulsifier-producing strain, Alcaligenes sp. S-XJ-1 could grow on waste diesel
      oil (WDO), dry weight of the strain was up to 2.0 g/L after being cultivated for
      7 d, 10 g/L S-XJ-1 cell suspension reduced surface tension of water from 72.0
      mN/m to 29.7 mN/m. Biodemulsifier produced by S-XJ-1 was 0.3 g/L, its critical
      micelle concentration (CMC) was 150 mg/L, showing a better surface activity than
      chemical surfactant SDS. Furthermore, it showed an demulsifying efficiency over
      70% for W/O model emulsion. It was indicated S-XJ-1 could utilize C14-C20 n
      alkanes composing waste diesel oil by GC-MS, C20 n-alkane was almost completely
      comsumed by S-XJ-1 with utilization ratio of 99%. In addition, n-alkanes
      utilization ratio and demulsifying capability increased when length of carbon
      chain increased. Both utilization ratio and demulsifying capability of
      biodemulsifier produced by S-XJ-1 using C20 n-alkane as the carbon source were
      superior to other n-alkanes, and similar to waste diesel oil. It was identified
      the biodemulsifier produced by S-XJ-1 using waste diesel oil was lipopeptide by
      TLC and FTIR.

PMID- 21072943
TI  - [Comparative analysis of primer-based PCR strategies for characterizing ammonia
      oxidizing bacterial communities in lake sediments].
AB  - PCR-based techniques are commonly used to characterize ammonia-oxidizing
      bacterial (AOB) communities, but are subjected to the bias induced by PCR
      primers. In this study, the sensitivity and specificity of two pairs of primer
      were assessed based on a group of lake sediment samples. Compared to the low
      sensitivity of the CTO primer, the betaAMO primer produced intensive single bands
      in all samples tested. However, the sequences retrieved from one of the samples
      by betaAMO did not cluster with Nitrosomonadales, to which all beta-AOB
      affiliate. In contrast, all sequences amplified with CTO fell within the
      Nitrosomonas europaea/"Nitrosococcus mobilis" lineage. Furthermore, the products
      of four approaches were subjected to denaturing gradient gel electrophoresis
      (DGGE), and the patterns of the nested strategies with betaAMO followed CTO or
      the universal primer of 16S rRNA gene followed CTO were highly similar to that of
      CTO amplification. These findings suggest that betaAMO is not competent for
      charactering the beta-AOB communities due to the low specificity. The nested
      approaches with both selective and specific primers are the choice because they
      can amplify effectively and retrieve community composition of beta-AOB in lake
      sediments.

PMID- 21072944
TI  - [Study on structural characterization and purification of bioflocculant ZS-7].
AB  - The bioflocculant ZS-7 was purified to homogeneity by ethanol precipitation,
      dialysis and gel permeation chromatography (GPC). About 0.98 g of the purified
      bioflocculant could be recovered from 1L of fermentation broth. The purified
      bioflocculant was identified as a glycoprotein consisting of polysaccharide
      (91.5%) and protein (8.4%), with an approximate molecular weight of 6.89 x 10(4).
      The major component of ZS-7 is an acid polysaccharide including uronic (16.4%),
      pyruvic (7.1%) and acetic acids (0.5%). It consists of galactose, glucose,
      mannose and rhamnose in a molar ratio of 142 :2.2 : 4.5 : 3.4. X-ray
      photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) and NMR
      spectrum of the bioflocculant indicate the presence of carboxyl, hydroxyl, amide,
      amino, methoxyl and sulfate groups.

PMID- 21072945
TI  - [Transthyretin-binding activity of hexabromocyclododecanes (HBCDs) and its
      thyroid hormone disrupting effects after developmental exposure].
AB  - In vivo and in vitro research approaches were carried out to survey the potential
      health risk of environmental exposure by hexabromocyclododecanes (HBCDs).
      Transthyretin-binding assay was designed to test for the potency of HBCDs to
      compete with thyroxine (T4) for binding to the transport protein. The results
      showed that the binding of 25I-T4 and T4 was only slightly inhabited even at the
      highest competitive concentration of HBCDs (75.08%, 80 micromol x L(-1)),
      indicating the marginally interfere potency of HBCDs in the transportation of T4.
      Sprague-Dawley rats of 3-days old were exposed to 0.2 mg/kg and 1 mg/kg HBCDs for
      21 d to examine the thyroid hormones (THs) disrupting effects of HBCDs after
      developmental exposure. Compared with the controls, levels of total 3,3',5
      triiodothyronine (TT3), free 3,3',5-triiodothyronine (FT3), increased
      significantly (p < 0.05, p < 0.05) in low- and high-dose exposures, thyroid
      stimulating hormone (TSH) also increased slightly while the total thyroxine
      (TT4), free thyroxine (FT4) had a decline about two-fold inversely. Combined both
      the in vivo and in vitro results, the possible mode of action of HBCDs on THs
      disruption may through the synergy or substitution effect of T3. The findings
      support further investigation of the potential THs disrupting effects of HBCDs on
      public health, especially on children during brain development.

PMID- 21072946
TI  - [Mechanism of quantum dots facilitating Cu2+-induced hepatic L02 cells toxicity:
      possible trojan-horse role of QDs].
AB  - Concerns regarding the potential environmental impact of quantum dots (QDs) are
      raised for its extensive use. Understanding the influences of QDs on original
      environmental pollutants induced toxicity and obtaining information about the
      mechanism is crucial to evaluate potential ecological hazards posed by QDs. The
      effects of QDs on Cu2+ induced Hepatic L02 cells toxicity and the mechanisms were
      investigated. IC10 value of 2 microg/mL QDs and IC10-IC50 value of 2.5-20
      microg/mL of CU2+ was used in this study. Firstly Luminescence emission spectrum
      of QDs showed 10 nm red shifts with addition of Cu2+ provide the interaction
      possibility of QDs and Cu2+, the further X-ray energy dispersive spectroscopy
      (EDX) analysis indicated binding of Cu2+ on QDs surface. Then the intracellular
      Cu2+ concentrations showed increase with addition of QDs, which is accompanied by
      loss of cell viability and morphology changes. The mechanism was therefore
      assumed as interaction of QDs-Cu2+ improved the intracellular Cu2+ level then
      cytotoxicity. QDs seemed to serve as Trojan-horse taking much more Cu2+ into
      cells via cheating cell membrane recognition, which imply the possible
      interactions with heavy metal ions will pose a significant influence on
      environment and human body.

PMID- 21072947
TI  - [Enzymatic hydrolysis of cellulose in reverse micelles].
AB  - Several types of surfactants were adopted to construct reverse micelles, in order
      to investigate the characteristics of cellulose hydrolysis, we used the
      carboxymethyl cellulose as substrate. The electrical conductivity was measured to
      determine the maximum water solubilization W0( W0 = [H2O]/[SA] ) of CTAB, SDS,
      Tween-80 and rhamnolipid reverse micellar systems were 15.2, 20.1, 2.3 and 40.3.
      In this condition we studied the effects of surfactants concentrations and
      cellulose dosage on the enzymatic hydrolysis of reverse micelle,and compared with
      aqueous systems. It was shown by the results that when the cellulose dosage was
      0.15 FPU/g substrate, the maximum yield of reducing sugar in reverse micelles was
      obtained at 1 cmc of CTAB, SDS, Tween-80 and rhamnolipid, in which the
      rhamnolipid yield was the highest of 198.03 mg substrate. When the concentrations
      of CTAB, SDS, Tween-80 and rhamnolipid were 1 cmc, the productions of reverse
      micelles systems were higher than that of aqueous systems of 34.36%, 21.24%,
      11.44% and 34.62%. In the optimum conditions of the surfactant concentration,
      taking the saving cost and sugar yield into consideration, the cellulose dosage
      of 5 FPU substrate was the most suitable. The reducing sugar's yield of
      biosurfactant rhamnolipid reverse micellar system was higher than those of three
      chemical surfactant systems, it was shown that the adoption of biosurfactant has
      technologically promising prospect in constructing reverse micelles and enhancing
      the stability of reverse micelles.

PMID- 21072948
TI  - [Effect of alkaline treatment on anaerobic digestion of rice straw].
AB  - The biogas yields of rice straw during anaerobic digestion can be improved by
      alkaline pretreatment, while it increased the cost because of large amount of
      alkaline. In order to decrease the amount, 3 sets of experiments were performed
      using straw with alkaline treatment (pretreatment), digested straw with alkaline
      treatment (post-treatment) and straw digested directly (control). The results
      showed that cell wall of straw was destroyed by 5% NaOH treated for 48h, the COD
      (chemical oxygen demand), total nitrogen, NO(3-) -N and NH(4+) -N were increased
      from 2 311.11, 175.40, 5.02 and 117.82 mg/L to 10488.89, 417.84, 248.64 and
      141.44 mg/L respectively. It suggested that not only lignocellulose but also some
      nitrogenous materials were destroyed or broken down by alkaline treatment. The
      lignin structure was destroyed through alkaline treatment that caused the
      decreased lignin, but the crystallinity index (C(r)I) of cellulose increased from
      0.592 3 to 0.662 2. The results of anaerobic digestion showed that the total
      solid of straw decreased 50.47% after anaerobic digestion treatment leading to
      less workload and only 50% alkaline used. However, the biogas yield of post
      treatment and pretreatment were 382.32 mL/g of TS(added) and 375.84 mL/g of
      TS(added). Lignin content of control increased while decreased in pretreatment
      and post-treatment. After anaerobic digestion, crystalline of cellulose was
      destroyed significantly, and crystalline and amorphous of post-treatment were
      destroyed more severely than that of pretreatment. From all those mentioned
      above, post-treatment of straw with alkaline was economical and feasible for
      biogas production.

PMID- 21072950
TI  - [Records and sources of mercury pollution over the past 200 years in Ny-Alesund,
      Arctic].
AB  - Hg pollution has become a global problem since the industrial revolution. In this
      study,we collected a pond sediment core rich in moss residues from the Ny-Alesund
      of Svalbard, and determined the content and flux of Hg in the sediments. Combined
      with 210Pb and 137Cs dating,we reconstructed the changes of Hg concentration and
      depositional flux in the recent 200 years,and focused on the main controlling
      factors on the elevated inputs of Hg since the 1850s. The results show that the
      Hg contents increase significantly since the World Industrial Revolution. The
      highest value of Hg is up to 180 ng x g(-1) in the surface sediments, and the
      ratios of anthropogenic Hg increase from 30% to 90%, thus the input of
      anthropogenic Hg has become a main source of total mercury in the study area. The
      range of Hg deposition flux is between 8-20 microg x (m(2) x a)(-1) in past 200
      years, and show three distinct peaks,corresponding to 1800 s, 1880 s and 1970 s.
      Compared the historical Hg deposition flux with the records of local coal
      combustion and globe Hg production, we suggest that the anthropogenic Hg is
      mainly derived from the long-range atmosphere Hg transport, whereas the influence
      of local coal mining is likely minor. The Ny-Alesund has similar Hg pollution
      degree with Sweden, Canada and other circum-arctic areas, but obviously higher
      than Greenland and significantly lower than America and Russia,as well as other
      industrialized countries.

PMID- 21072949
TI  - [Effect of the ratio of height to diameter on the performance of the simultaneous
      reactor for nitrogen removal from swine wastewater and sulfide removal from
      biogas].
AB  - The effect of the ratio of height to diameter (H/D) on the process of
      simultaneous nitrogen removal from swine wastewater and hydrogen sulfide removal
      from biogas was investigated, using the bubble column reactors with packing
      material. The performance of the reactor with H/D of 8 : 1, 3 :1 and 2 : 1 was
      compared. Under temperature of 30-32 degrees C, gas retention time of 6.70 min,
      hydraulic retention time of 3.35 d, hydrogen sulfide concentration of 1 414-1 838
      mg x m(-3) in biogas, and NO(x)(-) -N concentration of 114-243 mg x L(-1) in
      influent. The reactor with H/D of 2 : 1 achieved a stable and good treatment
      result, with the average removal rates of 96.7% for hydrogen sulfide, and 88.7%
      for N(x)(-) -N. While the reactors with H/D of 3 : 1 and 8 : 1 obtained unstable
      and inferior results, with the average removal rates of 68.0%, 80.4% for hydrogen
      sulfide respectively, and 89.7%, 90.2% for NO(x)(-) -N respectively. The reason
      could be attributed to the following facts. The reactor with H/D of 2:1 has a
      slower optimum gas velocity (3.12 x 10(-2) m x s(-1))- than the reactor with H/D
      of 3 : 1 and 8 : 1 (3.62 x 10(-2) m x s(-1) and 6.64 x 10(-2) m x s(-1)
      respectively), and has a higher gas-liquid mass transfer coefficient (1.79 x 10(
      5) s(-1)) than the other two reactors (1.64 x 10(-5) s(-1) and 1.55 x 10(-5) s(
      1) respectively). Results of the performance and the hydrodynamics parameters of
      the reactors all indicated that the reactor with H/D of 2 : 1 was more suitable
      for the process of simultaneous nitrogen and hydrogen sulfide removal.

PMID- 21072951
TI  - [Environment spatial distribution of mercury pollution in Songhua River upstream
      gold mining areas].
AB  - Using Zeeman mercury spectrometer RA915+ monitoring the total gaseous mercury
      concentration were collected from gold mining area in Huadian, in the upper
      reaches of the Songhua River, during summer and autumn of 2008, where we
      simultaneously collected samples of air, water, sediment and soil. The research
      is focused on analyzing of the spatial and temporal distribution characteristics
      of atmospheric mercury pollution and the correlation with other environmental
      factors. The results show that: the concentration of atmospheric mercury in
      summer is higher than that in autumn and in the evening is higher than at noon,
      and it present a gradual decay with the distance to the gold mining area as the
      center point increasing. The distribution rule of mercury pollution of
      environmental factors in the gold mining area is: in sediment > in soil > in
      plant > in water, the characteristics of mercury pollution distribution in plant
      is: root > stem and leaf, and the content of mercury in plant in autumn is
      commonly higher than that in summer. This is thought due to the accumulation of
      pollutant element from soil during the growth of plant. The atmospheric mercury
      has a significant correlation with the root of plant, respectively 0.83 in summer
      and 0.97 in autumn.

PMID- 21072952
TI  - [Distribution of Hg in mangrove plants and correlation with Hg speciation in
      sediments].
AB  - Plant is an important role in biogeochemical cycle of Hg. The aim of this study
      is to ascertain Hg accumulation in several kinds of mangrove plants, and to
      discuss relationship among Hg concentrations in mangrove plants and different Hg
      speciation in sediments. Contents of total mercury (THg) in mangrove plants and
      sediments were determined. Hg speciation was determined with a modified Tessier's
      method. Contents of THg of the mangrove plants were in the range of 817.5-3 197.6
      ng/g. In detail, Hg concentration was (1 579.4 +/- 1 326.8) ng/g in Kandelia
      candel, (2 115.1 +/- 1 892.3) ng/g in Aegiceras corniculatum, (2 159.3 +/- 1
      678.7) ng/g in Avicennia marina, (2 566.5 +/- 821.6) ng/g in Bruguiera
      gymnorrhiza, (2 104.3 +/- 1 661.8) ng/g in Excoecaria agallocha, (3 197.6 +/- 2
      782.8) ng/g in Sonneratia apetala, (817.5 +/- 632.3) ng/g in Acanthus
      ilicifolius, (1 801.8 +/- 1 255.4) ng/g in Rhizophora. stylosa, respectively.
      There are obvious interspecific variation, and organic variation in THg contents
      of mangrove plants, which is closely related to environment and physiological
      characteristics of mangrove plants. Enrichment of THg in mangrove plants was
      inhomogeneous, following the order of Sonneratia apetala > Bruguiera gymnorrhiza
      > Avicennia marina > Aegiceras corniculatum > Excoecaria agallocha > Rhizophora
      stylosa > Kandelia candel > Acanthus ilicifolius. Mercury exists mainly in
      volatile form in most mangrove wetlands, but mainly in the form of residue in
      sediments from Shenzhen mangrove wetlands. Significantly positive correlations
      were found among Hg concentrations in leaves and stems of Sonneratia apetala and
      volatile Hg, exchangeable Hg of sediments. Significantly positive correlations
      were also found among Hg concentrations in leaves of Excoecaria agallocha and
      volatile Hg, exchangeable Hg of sediments. But, there is no significant
      correlation between Hg concentrations of most mangrove plants and different Hg
      speciation in sediments. It showed that plants assimilate Hg from different
      sources, such as water, sediment and air, and that Hg assimilated by plants could
      transfer among different plant organics.

PMID- 21072953
TI  - [Effects of hydroxyapatite on growth and quality of potato (Solanum tuberosum L.)
      in Cd polluted soil].
AB  - A pot experiment was conducted in a glasshouse to study effects of hydroxyapatite
      amending Cd polluted soil on growth and quality of potato (Solanum tuberosum L.).
      In the experiment, 3 levels of Cd pollution (0, 5, and 10 mg x kg(-1)) and 6
      levels of hydroxyapatite application (0, 4, 8, 10, 16, and 30 g x kg(-1)) in soil
      were prepared to plant 2 potato varieties (Zhongshusanhao and Daxiyang in Chinese
      system). The results showed that Cd pollution in soil resulted in decrease in
      yield per plant of potato; for example, in the soils with 5 and 10 mg x kg(-1) of
      Cd, the yield per plant decreased 24%-31% and 41%-45%, respectively. Applying
      hydroxyapatite to Cd pollution could greatly increase yield per plant of potato.
      Compared to the soil without hydroxyapatite, 10 or 30 g x kg(-1) hydroxyapatite
      added to the soil with 5 or 10 mg x kg(-1) of Cd increased 17%-9% or 45%-58% in
      yield per plant. Due to hydroxyapatite amending Cd polluted soil, chlorophyll
      contents in leaves and superoxide dismutase (SOD) activities in tubers enhanced
      and malondialdehyde (MDA) contents in tubers declined apparently. Meanwhile,
      quality of potato tubers was obviously improved, such as increase in vitamin C
      contents, starch contents, and protein contents in potato tubers. With
      hydroxyapatite applying from 0 to 30 g x kg(-1), Cd contents in potato tubers
      deceased from 0.87-0.95 mg x kg(-1) to 0.13-0.21 mg x kg(-1) by 78%-85% in the
      soils with 5 mg x kg(-1) of Cd, and from 1.86-1.93 mg x kg(-1) to 0.52-0.65 mg x
      kg(-1) by 66%-72% in the soils with 10 mg x kg(-1) of Cd. The experiment
      indicated that the mechanism of hydroxyapatite alleviating soil Cd toxicity main
      included rising soil pH values, reducing effective Cd contents in soil, and Ca
      from hydroxyapatite blocking soil Cd moving to potato. However, ability of
      hydroxyapatite alleviating soil Cd toxicity was limited, and excessive
      hydroxyapatite to soil exhibited stress effects on growth and quality of potato.
      In the Cd polluted soils with proper hydroxyapatite, growth and quality of
      Zhongshusanhao were better than those of Daxiyang, indicating different responses
      of various potato varieties to environment amelioration.

PMID- 21072954
TI  - [Changes and analysis of soil quality under different land use types in oasis
      rim].
AB  - The aggravation process of oasisization leads to changes of land use type in
      oasis rim. In order to discuss the effects of different land use types on soil
      properties and soil quality, the four land use types located Cele oasis rim in
      south margin of Tarim Basin, which are the cotton field, orchard, and Caligonum
      mongolicum Turcz land use type reclaimed by people and nature state land use type
      covered by Alhagi sparsifolia SHAP, were selected as study object. The relative
      soil quality index (RI) and the soil quality synthesis index (SQI) were used to
      analyse the changes of soil quality between four land use types within 0-20 cm,
      2040 cm, 40-60 cm soil depth, respectively. Meantime, the fractal theory was used
      to analyse the particle-size distribution (PSD) property of top soil under
      different land use types. The results indicated that there was a significant
      difference in the soil organic matter and total nitrogen in same soil depth
      between four land use types; the order ranked according to RI was same to the
      order ranked according to SQI in each soil depth between four land use types. The
      cotton field and orchard have an obviously positive effect on soil quality of the
      top soil, however, the soil quality of Alhagi sparsifolia SHAP land use type was
      gradually increasing along with the increasing soil depth. The soil properties
      and soil quality of Caligonum mongolicum Turcz land use type were at the lowest
      level according to the comparison results among all land use types, and the
      calculation results of PSD fractal dimension also indicated the Caligonum
      mongolicum Turcz land use type had the worst ability on maintaining soil fine
      fractions.

PMID- 21072955
TI  - [Research progress of the coupling process of Fe and N in wetland soils].
AB  - The coupling process of the earth system is the key research content of earth
      surface system at present. Wetland is an important ecosystem on the earth
      surface. Wetland soil is under anaerobic conditions seasonally or perennially
      because of waterlogging, where the redox of Fe and N can be coupled by
      microbiology. The coupling process lies in three aspects: the microbial coupling
      of NO(3-)-reduction and Fe(2+)-oxidation, coupling of Fe(3+)-reduction and NH(4+)
      oxidation and the interaction of NO3- and Fe3+ during reduction. Getting the
      knowledge of the coupling process has important significance to understand the
      cycles of Fe and N in wetland soil. The article reviews the research status of
      the three aspects. In general, we have a comparatively deep understand of the
      coupling process of NO(3-)-reduction and Fe(2+)-oxidation than the latter two
      aspects. The research of microbial mechanism of the coupling process of Fe(3+)
      reduction-NH(4+)-oxidation and the comprehensive evaluation of the environmental
      significance of coupling process of Fe and N in wetland soil should be
      strengthened in the future research, and then it can provide evidence for wetland
      protection and management.

PMID- 21072956
TI  - [Perspectives on synergic biological effects induced by ambient allergenic pollen
      and urban fine/ultrafine particulate matters in atmosphere].
AB  - Ambient particulate matters (PM) and allergenic pollens in urban atmosphere have
      taken negative effects on human health and air quality. Studies on synergistic
      effects between the two pollutants are being focused in disciplines, such as
      atmospheric sciences, environmental toxicology, and immunology. In this study,
      physicochemical characterization of airborne fine/ultrafine particles in
      Shanghai, China and ambient allergenic pollens (cedar) in Kanto, Japan were
      investigated. We found that allergenic protein particles (Ubisch body) with
      diameter less than 0.7 microm were absorbed on Japanese cedar pollen, and
      airborne particles which contained allergenic particles mainly distributed in < 1
      microm size range. The highest mass concentration of chemical elements in
      Shanghai airborne particles was found in the 0.3-0.18 microm size range, but mass
      level of pollutant elements, such as S and Pb, in ambient in ultrafine (nano)
      particles were higher than that in coarse and fine particles. And also, pollen
      particles were found in Shanghai airborne particles. Synergistic effects between
      diesel exhaust particles (DEPs), which were the main component in urban airborne
      particles, and ambient pollens in urban atmosphere can be found, but their
      mechanism have not been clear. After our new results and other conclusions
      published recently on allergenic pollen and airborne fine/ultrafine particles
      were summarized, perspectives of this new discipline were presented.

PMID- 21072957
TI  - [Single embryo transfer].
AB  - Thanks to assisted reproduction technology (ART) most couples with infertility
      can be helped today. Since the beginning of ART, however, two major problems have
      existed. In the first years of IVF more than one embryo was transferred in order
      to reach acceptable pregnancy rates, but this entails a risk of multiple
      pregnancy with all its morbidity and mortality due to premature birth. Also,
      studies comparing the outcome of children following ART with the outcome of
      children who were spontaneously conceived, showed that ART increased the risk of
      prematurity and low birth weight, even in singleton pregnancies. The transfer of
      just one embryo (single embryo transfer or SET) in IVF/ICSI treatment cycles
      appeared to be the only answer to the epidemic of multiple pregnancies. The
      studies which analyze the outcome of SET singletons are promising, since they
      suggest that a broader application of SET could have a positive influence on the
      outcome of pregnancies after ART as well.

PMID- 21072958
TI  - [The anthropology of women in the Orthodox Jewish community of Antwerpen:
      identity, emancipation and integration].
AB  - This contribution contains a synthesis of the results of two socio-cultural
      anthropological research projects among Orthodox Jewry concerning the 'identity',
      'emancipation' and 'integration' of women. First the meaning of female
      religiosity from the perspective of strictly Orthodox, including Chassidic, women
      is discussed. Whereas in the public and institutional religious sphere men are
      the paradigmatic "Orthodox Jews", due to the sacralisatie of daily life,
      religious roles for women are not less extensive or any less important but are
      predominantly situated in the private and domestic sphere. It is argued that from
      an anthropological and gender critical perspective, women's religious gender
      identity therefore cannot be straightforwardly interpreted as either "oppressed"
      nor "emancipator". The second study concerns Jewish Orthodox women (ranging from
      strictly to modern Orthodox) in Antwerp who transgress religious gender norms by
      studying or working in the surrounding secular society. Their life stories show
      very different trajectories of encounters with the "outside world" that are
      sometimes enriching yet sometimes also experienced in terms of intercultural
      conflicts. It is concluded that maintaining cultural identity, next to
      emancipation and integration from within the Orthodox Jewish community is not
      impossible, but that this requires minimal mutual dialogue and understanding.

PMID- 21072959
TI  - [Cardiogenic shock--severe complication of myocardial infarction].
AB  - Cardiogenic shock is the most common fatal complication of acute myocardial
      infarction. The conception of an extensive irreparable myocardial injury
      underlying the cardiogenic shock has changed especially with the results of the
      SHOCK study. In addition to the infarction injury, an acute inflammatory
      reaction, neurohumoral activation as well as improving myocardial stunning
      influence the development of shock. Mortality is high at the initial stage,
      whereas subsequent prognosis is equivalent to that seen in other infarction
      patients. Essential therapy consists in a prompt revascularization of the
      infarcted area and optimization of hemodynamics, if necessary by applying
      mechanical supportive therapies.

PMID- 21072960
TI  - [Encephalopathies due to vitamin deficiency].
AB  - Encephalopathy may develop within 1 to 3 weeks upon cessation of thiamine supply.
      Deficiency of folic acid may require months until encephalopathy develops,
      whereas this may take years for vitamin B12 deficiency. It may be harmful for the
      patient if the impairment of cognitive functions is considered to be due to
      Alzheimer's disease, even though vitamin deficiency is the cause. Differential
      diagnosis, however, is not easy. Risk factors for vitamin deficiencies include
      reduction of body weight, associated surgical procedures and nausea during
      pregnancy.

PMID- 21072961
TI  - [Burnout among health care professionals].
AB  - Symptoms of burnout comprise exhaustion, cynicism, and diminished professional
      efficacy, as well as a feeling of impaired occupational achievement.
      Comprehensive Finnish studies have revealed that especially mild burnout is
      fairly common among clinicians and dentists. Burnout among clinicians accumulates
      to the public sector, to the early stages of the career, and to the specialties
      of psychiatry and radiology. Worker participatory methods aiming at the
      development of working conditions have yielded promising results in the
      prevention of burnout within the health care sector.

PMID- 21072962
TI  - [Cancer patient with dyspnoe--remember the possibility of pulmonary tumor
      microembolism].
AB  - We report two patients with breast cancer who presented with a subacute course of
      progressive dyspnoe and shortness of breathing, culminating in respiratory
      failure and cardiovascular collapse from acute right heart failure. D-dimer serum
      levels were elevated and right ventricle strain (electrocardiogram) and pulmonary
      hypertension were also present. Clinical investigation and computed tomography of
      the chest were inconclusive. The autopsy study revealed multiple intravascular
      carcinomatous emboli in small arterioles of pulmonary vasculature. In the
      differential diagnosis of unexplained severe dyspnoe and pulmonary hypertension,
      malignancy should always be kept in mind.

PMID- 21072963
TI  - [Update on current care guidelines. The diagnosis and medical treatment of memory
      disorders].
AB  - Any complaints from a patient about their memory should be examined. Diagnosis is
      based on international criteria. The basic evaluation consists of the medical
      history, clinical evaluation, cognitive tests and brain imaging, especially using
      MRI. When a diagnosis of Alzheimer's disease, AD with cerebrovascular disease or
      with Lewy Body disease, or Dementia associated with Parkinson's disease or LBD is
      made, evidence based medical therapy is indicated as part of comprehensive care.
      An acetylcholinesterase inhibitor or memantine can be used. These drugs are
      ineffective in the case of frontotemporal degenerations. For severe behavioural
      disorders, other psychoactive medications can be applied.

PMID- 21072964
TI  - [T-helper cells--bandleaders of immune response].
AB  - T-helper (Th) cells direct the actions of immune response by means of cytokines,
      soluble growth factors produced by them. Helper cells are divided into at least
      four different subtypes, dysfunctions of which may lead to disease states such as
      autoimmunity or asthma. Elucidation of regulatory mechanisms of the immune
      response has brought on the market biological drugs that are more effective and
      better tolerated than conventional drugs, such as antibodies inhibiting the
      action of cytokines. Since immune responses can be directed by affecting T-helper
      cell functions, research on T-helper cells is of interest for drug development.

PMID- 21072965
TI  - [Frontotemporal lobar degeneration: a diagnostic challenge].
AB  - Frontotemporal lobar degeneration (FTLD) is a common cause of dementia in
      population of under 65 years old. FTLD manifests clinically with progressive
      behavioural problems and personality changes and/or language impairment. There
      are no disease-modifying treatments for FTLD. Symptomatic treatments such as
      selective serotonin reuptake inhibitors and atypical antipsychotic agents are
      frequently used to manage behavioural symptoms. Immunohistochemical findings have
      clarified neuropathological classification of the disease. Family history of
      dementia is positive in approximately 30-50% of FTLD cases. Mutations in five
      different genes are known to cause FTLD, but these mutations seem to be rare in
      the Finnish population.

PMID- 21072966
TI  - [Future prospects of investigation into the cause of death].
AB  - While the total number of autopsies has steadily remained at 30 to 35% of all
      deaths, a change has occurred in the ratio of medical autopsies to forensic ones.
      The number of forensic autopsies has been on a steady rise since the 1980's. The
      most recent sectors of forensic medicine include applied molecular genetics and
      radiological imaging (virtopsy). Molecular autopsies and the virtopsy technique
      provide novel information that is inaccessible for the classical autopsy, but can
      be crucial for the determination of the cause and manner of death.

PMID- 21072967
TI  - [Eating disorders--transient nuisance or perpetual problem?].
AB  - Approximately 7% of Finnish women develop an eating disorder before the age of
      30. While at least 70% of anorectic women will recover from their illness,
      normalization of body weight and hormone function usually takes years. Some of
      the anorexia cases become chronic. Bulimia nervosa has been considered a milder
      disease than anorexia, but the disease picture of bulimia may fluctuate, often
      exhibiting highly prolonged symptoms. Psychotherapeutic treatment and medication
      produce good responses to bulimic symptoms, whereas evidence of the efficacy of
      anorectic therapies remains less certain.

PMID- 21072968
TI  - [Key points in stent grafting of the aortic arch].

PMID- 21072969
TI  - [LVAD placement in a patient in cardiogenic shock and with histories of omental
      filling for mediastinitis and open heart surgery repeated 5 times due to
      infective endocarditis].

PMID- 21072970
TI  - [Imaging diagnosis Q & A. The left coronary artery arising from the pulmonary
      trunk].

PMID- 21072971
TI  - Physicochemical characterization and drug-release properties of celecoxib hot
      melt extruded glass solutions.
AB  - The interest in hot-melt extrusion (HME) as a drug delivery technology for the
      production of glass solutions is growing rapidly. HME glass solutions have a
      tendency to recrystallize during storage and also typically have a very dense
      structure, restricting the ingress of dissolution fluid and retarding drug
      release. In this study, we have used HME to manufacture glass solutions
      containing celecoxib (CX) and polyvinylpyrrolidone (PVP) and have assessed the
      use of supercritical carbon dioxide (scCO2) as a pore-forming agent to enhance
      drug release. Differential scanning calorimetry confirmed the formation of glass
      solutions following extrusion. All extrudates exhibited a single glass transition
      temperature (Tg), positioned between the Tg values of CX and PVP. The instability
      of glass solutions is a significant problem during storage. Stabilization may be
      improved through the appropriate choice of excipient to facilitate drug-polymer
      interactions. The Gordon-Taylor equation showed that the Tg values of all
      extrudates expected on ideal mixing were lower than those observed
      experimentally. This may be indicative of drug-polymer interactions that decrease
      free volume and elevate the Tg. Molecular interactions between CX and PVP were
      further confirmed using Fourier transform infrared and Raman spectroscopy.
      Storage stability of the extrudates was shown to be dependent on drug loading.
      Samples containing a higher CX loading were less stable, which we ascribed to
      decreased Tg and hence increased mobility within the drug-polymer matrix. The
      solubility of CX was improved through the formulation of extruded glass
      solutions, but release rate was relatively slow. Exposure of extrudates to scCO2
      had no effect on the solid-state properties of CX but did produce a highly porous
      structure. The drug-release rate from extrudates after scCO2 exposure was
      significantly higher.

PMID- 21072974
TI  - [Emergency call: limits and risks].

PMID- 21072975
TI  - [Environment favorable to female physicians: introduction].

PMID- 21072973
TI  - Total intravenous anaesthesia (TIVA) with propofol-fentanyl and propofol
      midazolam combinations in spontaneously-breathing goats.
AB  - OBJECTIVE: To compare the efficacy and cardiopulmonary effects of propofol and
      fentanyl, with propofol and midazolam for total intravenous anaesthesia. STUDY
      DESIGN: Prospective, randomized, crossover experimental study. ANIMALS: Six
      goats; three does and three wethers. METHODS: Goats received either fentanyl 0.02
      mg kg(-1) (treatment FP) or midazolam 0.3 mg kg(-1) (treatment MP) intravenously.
      One minute later anaesthesia was induced with propofol, then maintained by
      constant rate infusion of propofol 12.0 mg kg(-1) hour(-1) and fentanyl 0.02 mg
      kg(-1) hour(-1) (treatment FP) or propofol 12.0 mg kg(-1) hour(-1) and midazolam
      0.3 mg kg(-1) hour(-1) (treatment MP) for 90 minutes. Response to noxious
      stimulus was tested every 10 minutes and propofol dose adjusted to prevent
      purposeful movement. Cardiopulmonary parameters were measured continuously, and
      arterial blood-gas analysis performed intermittently. Recovery was timed and
      quality scored. Results are presented as median (IQR). RESULTS: Differences in
      the propofol induction dose [4.00 (3.96-4.01) and 3.97 (3.91-4.00) mg kg(-1) for
      treatments FP and MP, respectively] were not significant. Quality of induction in
      both groups was smooth. The median propofol dose for maintenance was less (p =
      0.004) with treatment FP (12.0 mg kg(-1) hour(-1) than MP (18.0 mg kg(-1) hour(
      1). Cardiopulmonary function was well maintained with both treatments. Recovery
      times in minutes from the end of anaesthetic infusion for treatments FP and MP
      respectively were; to extubation 3.0 (3.0-3.0) and 4.5 (3.3-5.0); to sternal
      position, 4.5 (3.3-5.0) and 5.0 (5.0-6.5) and to standing 13.0 (10.3-15.0) and
      15.0 (11.3-17.3). Quality of recovery was acceptable in both groups, but abnormal
      behavioural signs were observed after treatment FP. CONCLUSIONS AND CLINICAL
      RELEVANCE: Total intravenous anaesthesia with propofol and fentanyl or propofol
      and midazolam, at the doses studied, in spontaneously-breathing, oxygen
      supplemented goats is practicable. Recovery from the fentanyl-propofol
      combination is not always smooth.

PMID- 21072976
TI  - [Environment favorable to female physicians (2): the status of female physicians
      in Japan].

PMID- 21072972
TI  - Use of pathway information in molecular epidemiology.
AB  - Candidate gene studies are generally motivated by some form of pathway reasoning
      in the selection of genes to be studied, but seldom has the logic of the approach
      been carried through to the analysis. Marginal effects of polymorphisms in the
      selected genes, and occasionally pairwise gene-gene or gene-environment
      interactions,are often presented, but a unified approach to modelling the entire
      pathway has been lacking. In this review, a variety of approaches to this problem
      is considered, focusing on hypothesis-driven rather than purely exploratory
      methods. Empirical modelling strategies are based on hierarchical models that
      allow prior knowledge about the structure of the pathway and the various
      reactions to be included as 'prior covariates'. By contrast, mechanistic models
      aim to describe the reactions through a system of differential equations with
      rate parameters that can vary between individuals, based on their genotypes. Some
      ways of combining the two approaches are suggested and Bayesian model averaging
      methods for dealing with uncertainty about the true model form in either
      framework is discussed. Biomarker measurements can be incorporated into such
      analyses, and two-phase sampling designs stratified on some combination of
      disease, genes and exposures can be an efficient way of obtaining data that would
      be too expensive or difficult to obtain on a full candidate gene sample. The
      review concludes with some thoughts about potential uses of pathways in genome
      wide association studies.

PMID- 21072977
TI  - [Environment favorable to female physicians (3): Results of a survey conducted
      among female members of the Japanese Society of Otorhinolaryngology].

PMID- 21072978
TI  - [Environment favorable to female physicians (4): approach to support female
      physicians at Jichi Medical University].

PMID- 21072979
TI  - Antiretroviral drug development for HIV: challenges for the future.
AB  - The scarcity of new innovative drugs in the development pipeline for combating
      HIV replication may signal a change in direction for HIV researchers and drug
      developers. The model of introducing drugs with incremental improvements within
      existing drug classes is no longer commercially viable. While an argument can be
      made that drugs aimed at novel targets may have a greater impact, the list of
      such targets is limited and the scientific challenge of intervening at another
      stage in the HIV replication cycle is high. It is difficult to envision a
      realistic risk/reward scenario that will ensure continued investment in the
      discovery of novel HIV drugs that simply block replication and suppress plasma
      viral load. Recently, it has been suggested that the scientific community should
      move research in a new direction, with the goal of attacking the reservoirs of
      latent HIV that persist despite treatment with current drugs to achieve a
      functional cure, if not a sterilizing cure. This process will have to be a long
      term commitment, primarily funded by the NIH, with some involvement by the
      pharmaceutical and biotechnology industries. While most individuals infected with
      HIV can achieve viral suppression with the current approved therapies, treatment
      is lifelong, side effects are significant and resistance will eventually render
      more of these drugs less effective. New and innovative approaches must be
      developed to prevent viral infection and further improve the quality of life for
      those individuals who are already infected.

PMID- 21072980
TI  - [Q & A: An esophageal lesion that tends to increase in size].

PMID- 21072983
TI  - Giovanni Orlandini--a representative of European anatomical science and culture.

PMID- 21072984
TI  - Spontaneously hypertensive rat neuroanatomy: applications to pharmacological
      research.
AB  - Spontaneously hypertensive rats (SHR), which are normotensive at birth and
      develop sustained hypertension between 3 and 6 months of age, are the model most
      extensively investigated for evaluating hypertensive brain damage and its
      treatment. The time-dependent rise of arterial blood pressure and the occurrence
      of brain atrophy, loss of nerve cells and glial reaction are shared to some
      extent with what occurs human hypertensive brain. SHR, therefore, can represent a
      reasonable model of hypertension-related brain damage. Our main studies on
      cerebrovascular and brain microanatomical changes occurring in SHR and their
      sensitivity to pharmacological interventions are summarized.

PMID- 21072985
TI  - Sarcoglycan[s] are not muscle-specific: hypothetical roles.
AB  - The sarcoglycan complex is a multimember transmembrane complex interacting with
      other proteins to provide a mechano-signaling connection from the cytoskeleton to
      the extracellular matrix in myofibers. This complex plays a key role at the
      membrane and is crucial in maintaining sarcolemma viability in muscle fibers.
      Recent observations have demonstrated that in the lung this glycoprotein is
      associated with both alveoli and bronchioles, and that the urogenital and
      digestive tracts are epsilon-sarcoglycan positive. Further addressing this issue,
      in this work we extend our previous studies to better verify whether the
      sarcoglycan complex also exists in epithelial tissue. All our observations showed
      staining for all sarcoglycans to be a normal pattern in all tested epithelial
      cells. We hypothesize a key role for sarcoglycans in bidirectional signaling
      between cells and extracellular matrix, and an important role in the regulation
      of inhibitory synapses and of blood brain barrier.

PMID- 21072986
TI  - Contacts between mast cells and dendritic cells in the human skin.
AB  - Langerhans cells are a dendritic cell type characteristic of the epidermis. Since
      mast cells secrete molecules potentially influent on dendritic cell
      differentiation, we have addressed the degree of proximity between these two cell
      types in biopsies of skin diseases characterized by massive influx of dendritic
      cell precursors. By fluorescence microscopy, avidin labeled mast cells were found
      in contact with CD1a+ dendritic cells. By electron microscopy, contacts between
      mast cells and blunty dendritic cells were found in areas corresponding to those
      where CD1a+ cells were localized by immunohistochemistry. We propose that mast
      cells can induce the differentiation of precursors into Langerhans cells through
      both the release of short range acting soluble factors and contact-mediating
      plasma membrane molecules.

PMID- 21072987
TI  - The aging brain, neuroinflammatory signaling and sleep-wake regulation.
AB  - Tissues and organs change over time, regulated by intrinsic (genetic)
      determinants and environmental (and microenvironmental) adaptation. Brain changes
      during lifetime are especially critical, as the brain is the effector of
      cognition and the vast majority of neurons live throughout the life of the
      individual. In addition, brain aging mechanisms are especially critical for
      disease vulnerability, given the aging-related prevalence of pathologies that
      include neurodegenerative diseases. In this context, the present contribution
      concisely highlights data yielded by recent trends of research on the normal
      aging brain, and specifically: the occurrence of synaptic changes (rather than
      neuronal loss) and the altered regulation of adult neurogenesis (which represents
      a novel exciting field of knowledge); the development of a low-grade chronic
      inflammatory state which primes glial cells and may lead to changes in
      intercellular crosstalk, thus playing a potential role in the brain
      susceptibility to neurodegeneration; changes occurring in state-dependent
      behavior, sleep and wake, which are products of global brain functioning and
      underlie consciousness and cognitive performance; changes in the biological
      clock, the hypothalamic suprachiasmatic nucleus, which regulates sleep-wake
      alternation and other endogenous rhythms. Altogether, the present synopsis of
      recent studies at the molecular, cellular, and functional levels emphasizes the
      idea that the normal aging brain should be viewed as an example of adaptation and
      plasticity rather than as an obligatory decline.

PMID- 21072988
TI  - Recent advances in molecular diagnostics of colorectal cancer by genomic arrays:
      proposal for a procedural shift in biological sampling and pathological report.
AB  - Two forms of genetic instability have been described in colorectal cancer:
      chromosomal instability, characterized by structural and numerical chromosomal
      abnormalities and associated to aneuploidy; and microsatellite instability,
      characterized by a deficiency in the mismatch repair system that leads to
      slippage in microsatellites and is associated to euploidy. Thirteen colorectal
      cancer sample DNAs were analyzed after colectomy. High-resolution genome-wide DNA
      copy number and Single Nucleotide Polimorphism genotyping analysis was performed
      by Affymetrix SNP 6.0 arrays that interrogates 906,600 single nucleotide
      polymorphisms and 945,826 copy number probes. We implemented this analysis as
      part of a routine procedure that includes the sampling of fresh tissue from the
      tumor mass without affecting the subsequent standard histopathological procedure.
      The novel molecular technology allows the determination of a genome-wide
      molecular karyotype using only 500 ng of high-quality tumor DNA; it distinguishes
      the two main types of genomic instability, discriminating between chromosomal
      instability positive and negative tumors. It also detects loss of heterozygosity
      (LOH) regions, called copy neutral-LOH. Tumor-associated copy neutral-LOH regions
      may play a pivotal role in oncogenesis when they determine duplications of either
      activating or loss of function gene mutation. We observed recurrent gains of
      chromosomes 2, 7, 8q, 9, 12, 13, 20 and losses of chromosomes 4, 5, 8p, 15, 17p,
      18, 22, and Y, in agreement with previous cytogenetic studies. The use of such
      sampling procedure could stimulate the routine detection of point mutations in
      specific genes, thus avoiding subsequent sectioning of formalin-fixed and
      paraffin-embedded samples.

PMID- 21072990
TI  - Atherosclerotic alterations in human carotid observed by scanning electron
      microscopy.
AB  - Atherosclerosis involves all the layers of the artery wall, but the events
      involving the intimal portion are fundamental to understand the evolution and
      gravity of lesions. This study shows that scanning microscopy is instrumental for
      better understanding the physiopathology of this disease.

PMID- 21072989
TI  - Anatomical basis of hypoxic and hyperoxic injuries to the centres of
      cardiorespiratory regulation.
AB  - The aim of the present paper is to briefly review the changes occurring in the
      nucleus tractus solitarii and carotid body in response to hypoxic and hyperoxic
      injuries. Selective alterations of dendrites and Fos-immunoreactivity of neurons
      have been observed in the subnucleus gelatinosus of the nucleus tractus solitarii
      of adult subjects dying after hypoxic-ischaemic injury. The selective
      vulnerability of this portion of the nucleus tractus solitarii may be explained
      mainly with reference to the vascularization of medullary tegmentum. In the
      carotid body, chronic hypoxia and hyperoxia cause a series of morphological,
      cellular and biochemical changes which may play a major role during the first
      postnatal period and may have implications in the pathogenesis of Sudden Infant
      Death Syndrome. Intermittent hypoxia may cause hypersensitivity of the carotid
      body, possibly increasing the risk of unstable respiration. Conversely, hyperoxia
      exposure has been reported to cause hyposensitivity and reduction in volume of
      the carotid body, possibly leading to ineffective response.

PMID- 21072991
TI  - Morphological changes induced by neuropeptide in vitro stimulation of the rat
      parotid gland.
AB  - The effect of in vitro stimulation of rat parotid gland with the neuropeptides
      substance P, calcitonin gene-related peptide and galanin has been studied by
      microfilament fluorescence staining and in semithin sections, and compared to
      control incubations and in vitro stimulation with beta-adrenergic and muscarinic
      agonists. Clear-cut aspects of massive granule exocytosis and cytoplasm
      vacuolation, indicative of protein and fluid secretion respectively, were obvious
      only after substance P stimulation, whereas treatment with galanin and calcitonin
      gene-related peptide produced little to no morphological changes. The results
      being in agreement with the outcome of other methodological approaches, these
      procedures appear reliable, may be effectively applied to the study of the
      functional regulation of secretory mechanisms, and may be particularly useful in
      human tissue analyses.

PMID- 21072993
TI  - Localization and origin of cardiac CD117-positive cells: identification of a
      population of epicardially-derived cells in adult human heart.
AB  - During heart morphogenesis, epicardial cells undergo epithelial-mesenchymal
      transition giving origin to a population of epicardially derived cells that play
      a crucial role in the development of most cardiac cell lineages. Considering the
      hypothesis that epithelial-mesenchymal transition of epicardial mesothelium can
      generate cardiac primitive cells in the adult heart, we have examined in vivo and
      in vitro the epicardium and subepicardium of normal human adult hearts and of
      pathological hearts from patients with chronic ischemic heart failure for the
      presence of CD117-positive cells with epithelial and mesenchymal markers
      expression. The number of CD117-positive cells increased significantly in the
      subepicardium of pathological hearts and sloped down towards myocardium,
      remaining still elevated with respect to normal hearts. While cells with typical
      epithelial proteins expression formed an intact layer on the surface of the
      normal hearts, CD117-positive cells were localized mainly in the subepicardium
      and expressed mesenchymal markers in the pathological hearts. Epithelial
      mesenchymal transition, induced in vitro by several growth factors known to
      accumulate in the ischemic myocardium, gave origin to epicardially-derived cells
      with CD117 expression. These data support the hypothesis of epicardial origin of
      cardiac primitive cells in the adult human heart.

PMID- 21072992
TI  - Adult stem cells, scaffolds for in vivo and in vitro myocardial tissue
      engineering.
AB  - The main goal in the last few years in cardiac research has been to isolate
      cardiac potential stem cells from adult myocardium and to demonstrate their
      differentiation potential. We have previously demonstrated that c-Kit positive
      cardiac stem cells are able to organize themselves into a tissue-like cell mass.
      In this 3D mass, they can produce a high concentration of natural extracellular
      matrix, can create vessels, a capsule and, with the help of an Open-pore
      Polylactic Acid scaffold, many cells can organize an elementary myocardium.
      Drawing from this background, we decided to design and use poly-lactic scaffolds
      and the model of the athymic Nude-Foxn1(nu) mouse to evaluate the extent of the
      myogenic vs endothelial differentiation in vivo, and to evaluate the presence or
      the absence of a foreign body reaction.

PMID- 21072994
TI  - Role of the B-cell receptor in chronic lymphocytic leukemia: where do we stand?
AB  - The past 15 years have witnessed an enormous effort in studying B-cell Chronic
      Lymphocytic Leukemia. A great number of researches brought significant novel
      information and a better understanding of the natural history of this disease.
      This mini review will focus on the studies related to the Immunoglobulin variable
      (IgV) genes rearrangements that compose the B-cell receptor (BcR) of the leukemic
      clones. These studies have defined a role for the antigen(s) in the paths that
      lead to leukemic clone generation/expansion and underscore the informative value
      represented by BcR analyses.

PMID- 21072995
TI  - Multipotent stem cells in the biliary tree.
AB  - The biliary tree system consists of two divisions: intrahepatic bile ducts and
      extrahepatic bile ducts. The development of the biliary tree, and secondarily the
      liver, shares a common origin with ventral pancreas. A common progenitor for
      liver, biliary duct system, and ventral pancreas exists at early stages of
      development, when the anterior definitive endoderm is forming the foregut.
      Several studies indicate that the biliary tree contains stem cell compartments
      for liver, pancreas and the bile duct system and persisting into adulthood. These
      stem cell compartments are present in the peribiliary glands and possibly give
      rise to committed progenitors in gallbladder that does not have peribiliary
      glands. The biliary tree stem/progenitors represent a new source of cells that
      can be used as tools for regenerative medicine of liver, bile duct and pancreas.

PMID- 21072996
TI  - Plasticity and regeneration in the peripheral nervous system.
AB  - While in the central nervous system plasticity (in response to stimulus) and
      regeneration (in response to injury) are mainly based on adaptive changes in
      neural circuitries and synaptic reorganization, in the peripheral nervous system
      they are predominantly based on axonal (re)growth and neuron addition. In this
      paper, we will briefly overview the main investigation lines on plasticity and
      regeneration in the peripheral nervous system that have been carried out at the
      Laboratory of Human Anatomy of the Department of Clinical and Biological Sciences
      at the "San Luigi Gonzaga" Medical Faculty of the University of Turin. This body
      of research was mainly focused on the identification of the adaptive changes
      occurring to the sensory and autonomic neurons as a consequence of exceptional
      stimuli and/or damage at their periphery, as well as on the identification of
      effective new strategies for improving post-traumatic peripheral nerve fiber
      regeneration. These studies are in line with the long standing tradition on
      peripheral nervous system investigation carried out by the Anatomical School at
      the University of Turin since the times of Giuseppe Levi and we are honoured to
      have the occasion to present the results of our research on occasion of the
      appointment of Giovanni Orlandini as Emeritus Professor of the University of
      Florence.

PMID- 21072997
TI  - Characterization of oligodendrocyte lineage precursor cells in the mouse cerebral
      cortex: a confocal microscopy approach to demyelinating diseases.
AB  - The identification of stem cells resident in the adult central nervous system has
      redirected the focus of research into demyelinating diseases, such as multiple
      sclerosis, mainly affecting the brain white matter. This immunocytochemical and
      morphometrical study was carried out by confocal microscopy in the adult mouse
      cerebral cortex, with the aim of analysing, in the brain grey matter, the
      characteristics of the oligodendrocyte lineage cells, whose capability to
      remyelinate is still controversial. The observations demonstrated the presence in
      all the cortex layers of glial restricted progenitors, reactive to A2B5 marker,
      oligodendrocyte precursor cells, expressing the NG2 proteoglycan, and pre
      oligodendrocytes and pre-myelinating oligodendrocytes, reactive to the specific
      marker O4. NG2 expressing cells constitute the major immature population of the
      cortex, since not only oligodendrocyte precursor cells and pre-oligodendrocytes
      but also a part of the glial restrict progenitors express the NG2 proteoglycan.
      Together with the population of these immature cells, a larger population of
      mature oligodendrocytes was revealed by the classical oligodendrocyte and myelin
      markers, 2',3'-cyclic nucleotide 3'-phosphodiesterase, myelin basic protein and
      myelin oligodendrocyte glycoprotein. The results indicate that oligodendrocyte
      precursors committed to differentiate into myelin forming oligodendrocytes are
      present through all layers of the adult cortex and that their phenotypic features
      exactly recall those of the oligodendroglial lineage cells during development.

PMID- 21072998
TI  - Effects of estrous cycle and xenoestrogens expositions on mice nitric oxide
      producing system.
AB  - Nitric oxide (NO)-containing neurons are widely distributed within the central
      nervous system, including regions involved in the control of reproduction and
      sexual behavior. Nitrergic neurons may co-localize with gonadal hormone receptors
      and gonadal hormones may influence neuronal NO synthase expression in adulthood
      as well as during development. In rodents, the female, in physiological
      conditions, is exposed to short-term changes of gonadal hormones levels (estrous
      cycle). Our studies, performed in mouse hypothalamic and limbic systems, reveal
      that the expression of neuronal NO synthase may vary according to the rapid
      variations of hormonal levels that take place during the estrous cycle. This is
      in accordance with the hypothesis that gonadal hormone activation of NO-cGMP
      pathway is important for mating behavior. NO-producing system appears
      particularly sensitive to alterations of endocrine balance during development, as
      demonstrated by our experiments utilizing perinatal exposure to bisphenol A, an
      endocrine disrupting chemical. In fact, significant effects were detected in
      adulthood in the medial preoptic nucleus and in the ventromedial subdivision of
      the bed nucleus of the stria terminalis. Therefore, alteration of the neuronal NO
      synthase expression may be one of the causes of the important behavioral
      alterations observed in bisphenol-exposed animals.

PMID- 21073000
TI  - The gastric wall in systemic sclerosis patients: a morphological study.
AB  - Organ failure secondary to fibrosis is the main cause of morbidity and death in
      patients with systemic sclerosis. Gastrointestinal tract dysmotility is a major
      visceral manifestation, clinically ranging from an asymptomatic form to severe
      paresis. Although the oesophagus is the most frequently affected part of the
      gastrointestinal tract, all other segments can be involved. The present study was
      undertaken to evaluate the histopathological changes of the gastric wall in a
      series of full-thickness biopsies from systemic sclerosis patients who underwent
      gastric surgery due to severe gastroesophageal involvement. Gastric biopsies were
      processed for light microscopy and transmission electron microscopy. The
      histological and ultrastructural observations revealed a generalized fibrosis
      affecting all the gastric wall layers. The most severe changes were observed in
      the muscularis mucosae and muscle layers. Wide areas of marked focal fibrosis
      with dense collagen bundles and elastic fibre deposition surrounding smooth
      muscle cells were found. Myofilaments and thickened dense bodies were severely
      disarranged or absent in most smooth muscle cells. Nerve fibres showed
      ultrastructural alterations, such as oedematous axoplasm and scarce cytoskeletal
      elements. Abundant elastic and collagen fibres enveloped nerve fibres, nerve
      endings and interstitial cells of Cajal, thereby separating them from smooth
      muscle cells and blood microvessels. This study provides evidence for a prominent
      fibrosis and severe ultrastructural alterations of smooth muscle cells and nerve
      fibres as the main histopathological hallmarks in the gastric wall of systemic
      sclerosis patients.

PMID- 21072999
TI  - Morphological expression of angiogenesis in the mammalian ovary as seen by SEM of
      corrosion casts.
AB  - In the mammalian ovary, follicular and corpus luteum cycle is associated with
      intensive microvascular remodelling. The complex angiogenic dynamics are finely
      tuned by numerous regulatory factors acting as activators (up-regulators) or
      inhibitors (down-regulators) of angiogenesis. Alterations of such a tight
      modulation are involved in several pathologies, including infertility, polycystic
      ovarian syndrome, ovarian hyperstimulation syndrome and ovarian cancer. We have
      demonstrated in several experimental models that ovarian function is critically
      and specifically dependent on angiogenesis for follicular development, ovulation,
      and corpus luteum growth. The aim of this review is to summarize the results we
      have obtained on the morphodynamic remodelling of ovarian microvascularization,
      in polyovulatory (rat, rabbit and pig) and monovulatory species (cow), using
      scanning electron microscopy of vascular corrosion casts. The knowledge of the
      morphological expression of the up- and down-regulation of angiogenesis occurring
      in mono and polyovulatory animals might provide useful information to preserve
      fertility and to increase of the effectiveness of reproductive management in
      species of domestic interest.

PMID- 21073001
TI  - Static and dynamic osteogenesis.
AB  - Two subsequent different types of bone formation, we respectively named static
      osteogenesis (SO) and dynamic osteogenesis (DO), were observed in intramembranous
      ossification centers of newborn rabbits and chick embryos as well as during bone
      repair. In all cases the onset of intramembranous ossification is characterized
      by the appearance, around the vessels, of pluristratified cords of unexpectedly
      stationary osteoblasts that transform into osteocytes in the same site where they
      differentiated, whence the name of static osteogenesis (SO). Soon after, typical
      monostratified laminae of well known movable osteoblasts differentiate along the
      surface of the bony trabeculae laid down by SO and thicken them by DO. No
      significant structural and ultrastructural differences were found between
      stationary and movable osteoblasts, all being polarized secretory cells joined by
      gap junctions. However, unlike in typical movable osteoblast laminae, stationary
      osteoblasts inside the cords are irregularly arranged, variously polarized, and
      transform into osteocytes clustered within confluent lacunae. Briefly SO seems to
      be devoted to building the first trabecular bony framework having, with respect
      to the subsequent bone apposition by typical movable osteoblasts, the same
      supporting function as calcified trabeculae in endochondral ossification. SO-bone
      is a bad quality woven-bone, whereas DO-bone generally is a lamellar-bone and
      thus mechanically more resistant. The relevance of this fact in bone repair and
      clinical practice will be discussed.

PMID- 21073002
TI  - Cell behaviour on bioactive polymeric coatings.
AB  - Researchers are testing different treatments to induce modifications in both
      chemical composition and topography of implant surface, with the aim to
      ameliorate bone-to-implant contacts and hence improve osseointegration processes
      and biomechanical properties in the short and long-term. Aim of the present
      research was the evaluation of MG63 osteoblast-like cells behaviour on polymeric
      coatings, electrosynthesized on titanium substrates, differently modified in
      order to improve implant performances both in terms of osseointegration and
      infection prevention. Cell viability data and scanning electron microscopy
      morphological observations were consistent with a good compatibility of modified
      electrosynthesized coatings and suggest the use of this procedure to produce new
      bioactive titanium coatings for implant surgery.

PMID- 21073003
TI  - Pro-calcific responses by aortic valve interstitial cells in a novel in vitro
      model simulating dystrophic calcification.
AB  - Etiopathogenetic mechanisms in calcific aortic valve stenosis are still poorly
      understood despite this being the third major cause of heart disease in western
      world. In prior in vitro cultures simulating metastatic calcification, pro
      calcific effects on aortic valve interstitial cells (AVICs) resulted by adding
      bacterial endotoxin lipopolysaccharide (LPS) at high inorganic phosphate (Pi)
      levels. Here we accomplished improved in vitro models simulating either
      metastatic (Pi = 2.6 mM) or dystrophic calcification (Pi = 1.3 mM), in which LPS
      stimulated bovine AVICs underwent extra-stimulation with macrophage-cytokine
      containing media derived from parallel cultures of allogeneic
      monocyte/macrophages in turn stimulated with LPS. In dystrophic calcification
      like cultures, lower calcium amount was spectrometrically assessed with parallel
      reduced alkaline phosphatase activity with respect to metastatic calcification
      like cultures, with an about three-fold slower progression of mineralization.
      Hydroxyapatite crystal precipitation was ultrastructurally found to correlate
      with AVIC degeneration processes culminating with the formation of phthalocyanin
      positive lipidic layers (PPLs) at the surface of cells and cell-derived matrix
      vesicle-like bodies, acting as calcium nucleators according to a pattern
      mirroring those we had previously found in in vivo conditions. In conclusion, an
      in vitro model has been developed enabling reliable simulations of the effects
      exerted on AVICs by putatively pro- or anti-calcific agents.

PMID- 21073004
TI  - Three-dimensional analysis of facial morphology: growth, development and aging of
      the orolabial region.
AB  - Soft tissue analysis plays an increasing, strategic role in the recognition of
      facial alterations, but there are scanty three-dimensional reference data during
      normal growth, development and aging. In the current study, 532 male and 386
      female healthy subjects aged 4 to 73 years were analyzed using a non-invasive,
      computerized electromagnetic digitizer, and normal dimensions of mouth and lips
      were obtained in the three-dimensional space. Labial thickness and curvature were
      also assessed in a selected group of 40 men and women, equally divided into young
      (age 21-30 yr, mean 25 yr) and old persons (age 45-65 yr, mean 55 yr). Lip
      vermilion area to volume, and vermilion height to cutaneous lip height ratios
      decreased with age in both sexes. On average, the lips were thicker in men and in
      young persons than in women and in old persons. Mean labial curvature was larger
      in young men than in the other groups, and it was more variable in young than in
      old persons. Data collected in the present investigation can be used as a data
      base for the quantitative description of human lip morphology during normal
      growth, development and aging.

PMID- 21073005
TI  - The many faces of S100B protein: when an extracellular factor inactivates its own
      receptor and activates another one.
AB  - The Ca(2+)-binding protein of the EF-hand type, S100B, is an intracellular
      regulator and an extracellular signal. Within cells S100B interacts with several
      proteins thereby regulating energy metabolism, Ca2+ homeostasis, protein
      phosphorylation and degradation, and cell locomotion, proliferation and
      differentiation. Once secreted/released, S100B exerts autocrine and paracrine
      effects on responsive cells by engaging the receptor for advanced glycation end
      products. However, recent evidence suggests that S100B might also activate basic
      fibroblast growth factor receptor 1 via prior binding to basic fibroblast growth
      factor.

PMID- 21073006
TI  - Stress proteins in experimental nephrotoxicity: a ten year experience.
AB  - Heat shock proteins and glucose-regulated proteins represent an extraordinary
      mechanism of defense induced in the kidney by chemicals or drugs and essential to
      survive. Here we resume our experience on the presence and regulation of stress
      proteins into acute and chronic nephrotoxic models in rodents and in vitro. In
      acute renal damage, induced in rats by a single injection of inorganic mercury,
      stress proteins enhanced in a dose-dependent manner to recover cytoskeleton and
      mitochondria and maintain nuclear activity. When we pre-treated mercury injected
      rats with antioxidant melatonin or with bimoclomol, a stress proteins-coinducer,
      stress proteins expression was modulated together with tubular recovery. Similar
      data were obtained in ischemia-reperfusion in rats treated with stannous
      chloride, that provided cytoprotection stimulating heme oxygenase induction.
      During nephrotoxicity induced by administration of cyclosporine A at therapeutic
      dosage for 1-2 months, stress protein overexpression well correlated with
      oxidative and cell death, but decreased if we counteracted renal damage using
      antioxidants. In aluminium intoxication through drinking water for 3-6 months, we
      detected a time-dependent stress response in the rat kidney that was organ
      specific and different from the liver. In vitro studies on rat tubular proximal
      cells exposed to heavy metals demonstrated that stress protein expression was
      related to peculiar mechanisms of action of each metal. In conclusion,
      experimental studies on the renal chaperones can greatly contribute to understand
      their role, and agents able to modulate the stress response might be considered
      promising therapeutic tools to reduce nephrotoxicity.

PMID- 21073008
TI  - New occasions teach new duties.

PMID- 21073007
TI  - Presence and interaction in tissues of atrial natriuretic peptide, oxytocin and
      vasopressin: new insights.
AB  - Atrial natriuretic peptide, oxytocin and vasopressin are three well known and
      widely studied molecules since many years. They have been fully characterised
      from a genetic and biomolecular point of view and a number of receptor-dependent
      functions have been recognised for them. Nevertheless, in the last years our
      group has conducted morphologic studies, using an immunohistochemical approach
      complemented by molecular biology techniques, and could show non-canonical
      localization and co-localization of these peptides in normal and pathologic
      tissues, that permitted us to postulate that they may be involved in a wider
      range of functions than usually assumed and not yet fully understood. In this
      minireview we summarise some of the main results that open new scenarios in the
      comprehension of the biologic activities of these peptides and allow to postulate
      a role for them as diagnostic tools.

PMID- 21073009
TI  - The origins of the medical institution of Yale College.

PMID- 21073010
TI  - The Clements C. Fry collection at Yale.

PMID- 21073011
TI  - Pre-medical education for future physicians: evolution at Yale and beyond.

PMID- 21073012
TI  - Medical education: progress and retreat.
AB  - In summary, there have been significant educational improvements, particularly
      during the first two years of medical school. Students today are more
      accomplished, more diverse, and there is now a focus on the highly relevant basic
      science of medical practice, including medical ethics and public health. The
      curriculum has been centralized and coordination between various departments has
      vastly improved as a result. The number of lectures has been reduced, replaced by
      more effective small-group, problem-solving seminars. Support services for
      students have made medical school a much more enjoyable experience. On the other
      hand, the dramatic shift in the nature of hospitalized patients has adversely
      affected traditional bedside teaching that was such an important part of clinical
      education in the past. Extensive diagnostic evaluations now take place in an
      ambulatory setting. Hospitals and medical schools have not yet found a
      satisfactory way to integrate trainees into these venues. Finally, there has been
      a marked decrease in the number of graduates seeking careers in primary care, a
      phenomenon influenced by huge educational debts, the attraction of being able to
      master a defined discipline, and the desire to combine a medical life with a
      reasonable life-style. On balance, although the overall education of our future
      doctors has definitely been improved in the past fifty years, the erosion in
      fundamental clinical skills has been a disappointment.

PMID- 21073013
TI  - Medical student-to-associate dean at Yale.

PMID- 21073014
TI  - The Yale Department of Internal Medicine 1952-1965.

PMID- 21073016
TI  - Recollections on government and health care.

PMID- 21073015
TI  - The role of the Yale affiliated Gastroenterology Program in the evolution of
      medical education in Connecticut.

PMID- 21073017
TI  - The way we were--at Yale.

PMID- 21073018
TI  - The history and development of the Department of the History of Science and
      Medicine of Yale University. 1960.

PMID- 21073019
TI  - Educating doctors.

PMID- 21073020
TI  - Through her eyes.

PMID- 21073021
TI  - Putting yourself in your patient' shoes.

PMID- 21073022
TI  - Changes in platelet count in uncomplicated and severe falciparum malaria.
AB  - This study investigated alterations in platelet counts pre- and post-treatment
      with artemisinin derivatives in uncomplicated and severe falciparum malaria.
      Serial platelet counts were taken over 4 weeks for 110 uncomplicated and 110
      severe falciparum malaria patients admitted to the Hospital for Tropical Diseases
      during 2005-2008. On admission, prior to treatment, thrombocytopenia was found in
      73.6% of uncomplicated falciparum malaria patients and 90.9% of severe falciparum
      malaria cases. Platelet levels significantly lower in severe malaria cases.
      Although initial platelet counts were lower than normal in both study groups,
      they slowly increased significantly over time, and approached normal levels by
      several weeks post-treatment. No bleeding was evident during treatment, and none
      of the patients required a platelet transfusion. Platelet transfusions are not
      required for malaria patients with thrombocytopenia who have no bleeding.

PMID- 21073023
TI  - Factors associated with acute renal failure in severe falciparum [corrected]
      malaria patients.
AB  - Acute renal failure (ARF) is a common cause of morbidity and mortality in severe
      malaria infection. We evaluated factors associated with acute renal failure in
      severe malaria by comparing patients with severe malaria with and without ARF
      admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. Nine hundred
      fifteen severe malaria patients were included in the study, of whom 195 had ARF
      and 720 did not have ARF. We found jaundice, anemia, hypoalbuminemia,
      hyponatremia, hyperkalemia, acidosis, leukocytosis, elevated transaminases (SGOT
      and SGPT) and cerebral malaria, were significantly associated with ARF among
      patients with severe malaria (p < 0.05). Patients who have ARF and any of these
      clinical or laboratory manifestations of severe malaria should be monitored and
      managed properly, since early detection and treatment may reduce morbidity and
      mortality.

PMID- 21073025
TI  - Is Sabin-Feldman dye test using T. gondii tachyzoites from animal inoculation
      still the best method for detecting Toxoplasma gondii antibodies?
AB  - Although the Sabin-Feldman dye test is the gold standard for detecting Toxoplasma
      antibodies in human, it is performed only in reference laboratories because live
      virulent T. gondii are used for the test. We collected 210 human serum samples
      and tested them by the dye test using in vivo tachyzoites (conventional method)
      then compared these results with three other methods: a dye test using cell
      culture-derived T. gondii tachyzoites and indirect immunofluorescent antibody
      tests (IFAT) using in vivo and in vitro tachyzoites. We found the conventional
      dye test detected the highest percent of cases (4.3%), followed by the IFAT using
      parasites from mice (3.8%), then the dye test and the IFAT using cell culture
      tachyzoites (both 2.8%). Agreement with the dye test when using mouse and cell
      culture derived tachyzoites was 96.7%. Using in vivo tachyzoites for the dye test
      and the IFAT gave 94.3% agreement, while using in vitro tachyzoites gave 94.8%
      agreement. When compared with the conventional dye test, the IFAT had 75%
      sensitivity and 100% specificity. The T. gondii tachyzoites obtained from cell
      culture had a lower virulence, as indicated by a three times longer survival
      period in the inoculated mice. We favor the conventional dye test as the gold
      standard for Toxoplasma antibody detection. In vitro tachyzoites can be used
      routinely in the dye test but false negative results may occur in some cases. The
      IFAT, using either in vivo or in vitro tachyzoites, are alternatives for
      laboratories where provision of live tachyzoites is limited.

PMID- 21073024
TI  - An alternative liquid chromatography-mass spectrometric method for the
      determination of azithromycin in human plasma and its application to
      pharmacokinetic study of patients with malaria.
AB  - A simple, sensitive, selective and reproducible method based on high performance
      liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/MS)
      was developed for the determination of a macrolide antibiotic azithromycin in
      human plasma. The internal standard (roxithromycin) was separated from
      azithromycin on a Hypersil Gold C18 column, with retention times of 10.71 and
      13.67 minutes, respectively. The mobile phase consisted of a mixture of 20 mM
      ammonium acetate buffer (pH 5.2), acetonitrile and methanol (50:40:10, v/ v/v),
      running through the column at a flow rate of 0.3 ml/minute. Chromatographic
      analysis was carried out at 25 degrees C. Sample preparation was by liquid-liquid
      extraction with a mixture of 7:3 (v/v) diethylether:dichloromethane. The
      precision of the method based on within-day repeatability and reproducibility
      (day-to-day variation) was below 5% (% coefficient of variations: % CV). Good
      accuracy was observed for both intra-day and inter-day assays. The limit of
      quantification was acceptable at 0.5 ng using 200 microl plasma samples. The mean
      recoveries for azithromycin and the internal standard were greater than 85%. The
      method was applied successfully to the investigation of the pharmacokinetics of
      azithromycin when given in combination with fosmidomycin as oral doses of 750 mg
      twelve hourly for 3 days in 5 Thai male patients with acute uncomplicated
      falciparum malaria.

PMID- 21073026
TI  - Eosinophilic appendicitis caused by Schistosoma japonicum: a case report and
      review of the literature.
AB  - Parasitic appendicitis is uncommon. The authors reviewed the pathology of 4,130
      appendices resected over the past 10 years (2000 to 2009). Only one case of
      eosinophilic appendicitis caused by Schistosoma japonicum was identified. The
      overall prevalence of schistosomal appendicitis was 0.024%. The case was a 61
      year-old woman who presented with right lower quadrant abdominal pain. She had
      been a farmer in Chumphon and Surat Thani Provinces, which are endemic for
      schistosomiasis in Thailand. Physical, laboratory and ultrasound examinations
      were suggestive of acute appendicitis. She underwent emergency appendectomy.
      Intraoperative findings revealed a ruptured appendix with a fecalith in the
      appendiceal lumen. The histopathologic diagnosis was suppurative eosinophilic
      appendicitis with schistosomal ova in the mucosa, submucosa, muscular layer and
      vascular lumens, identified as S. japonicum eggs. The patient was treated for the
      parasite with praziquantal. We briefly review the clinicopathologic features and
      pathogenesis of schistosomal appendicitis.

PMID- 21073027
TI  - Aedes albopictus control with spray application of Bacillus thuringiensis
      israelensis, strain AM 65-52.
AB  - A Bacillus thuringiensis israelensis (Bti) formulation, VectoBac WG (strain AM 65
      52), was evaluated for mosquito control in a training area with dense vegetation.
      Bti was spray applied to target Aedes albopictus larval habitats of 130 ha once
      every 2 weeks using a motorized back pack mist blower, Stihl SR420, and a vehicle
      mounted ultra low volume generator (ULV), IGEBA U40. Ovitrap index (OI) and
      larval density (LD) were used to measure the efficacy of larviciding. In the Bti
      treated area the OI and LD significantly decreased with time (p < 0.05); OI
      decreased from 84.3 +/- 1.7 to 27.5 +/- 2.5 (%) and LD decreased from 27.9 +/-
      1.5 to 3.2 +/- 1.8 larvae per ovitrap by 3 months from the start of treatment.
      During the same period of time there was no significant reduction in OI and LD at
      the untreated site which was under a conventional mosquito control program. This
      large scale study indicates larvicidal spraying with Bti of natural breeding
      sites, was able to reduce Ae. albopictus adult density. This significant
      reduction was not achieved with conventional manual application methods.

PMID- 21073028
TI  - Laboratory evaluation of four commercial repellents against larval
      Leptotrombidium deliense (Acari: Trombiculidae).
AB  - Four commercial repellents were evaluated in the laboratory against
      Leptotrombidium deliense chiggers. Both in vitro and in vivo methods were used to
      determine repellency of the compounds. The repellents were Kellis (containing
      citronella oil, jojoba oil and tea tree oil), Kaps (containing citronella oil),
      BioZ (containing citronella oil, geranium oil and lemon grass oil) and Off
      (containing DEET). The combination of three active ingredients: citronella oil,
      geranium oil, lemon grass oil gave the highest repellency (87%) followed by DEET
      (84%). In vitro repellencies ranged from 73% to 87%. There was no significant
      difference between the four products. All the repellents had 100% in vivo
      repellency compared to 41-57% for the controls.

PMID- 21073029
TI  - Application of revised dengue classification criteria as a severity marker of
      dengue viral infection in Indonesia.
AB  - A prospective study of dengue infected patients at Dr.Soetomo Hospital pediatric
      ward was carried out from October 2008 to April 2009 to evaluate the revised
      dengue classification system proposed by the Dengue Control (DENCO), for early
      detection of severe dengue infected patients using the WHO classification system
      for comparison, with the addition of clinical interventions as a tool to grade
      for severity. One hundred forty-five patients were included in the study. Using
      the WHO classification system, 122 cases (84.1%) were classified as having non
      severe dengue, of which 70 (48.3%) were classified as having dengue fever (DF),
      39 (26.9%) as having dengue hemorrhagic fever (DHF) grade I, and 13 (9%) as
      having DHF grade II. Twenty-three (15.9%) were classified as having severe
      dengue, of which 16 (11%) were classified as having DHF grade III and 7 (4.8%) as
      having DHF grade IV. With clinical interventions included, 8 cases (6.6%)
      originally classified as having non-severe dengue infection were reclassified as
      having severe infection (sensitivity = 74%, specificity = 100%, likelihood ratio
      (-) = 0.26). Using the new dengue classification system, 117 cases (80.7%) were
      classified as having non-severe dengue infection, of which 79 (54.5%) were
      classified as having dengue without warning signs and 38 (26.2%) were classified
      as having dengue with warning signs, while 28 (19.3%) were classified as having
      severe dengue infection. Using clinical intervention, 4 cases (3.4%) which were
      originally classified as having non-severe dengue infection were reclassified as
      having severe dengue infection (sensitivity = 88%, specificity = 99%, likelihood
      ratio (+) = 98.88, likelihood ratio (-) = 0.13). Binary logistic regression
      showed the revised dengue classification system (p = 0.000, Wald:22.446) was
      better in detecting severe dengue infections than the WHO classification system
      (p = 0.175, Wald:6.339).

PMID- 21073030
TI  - Seroprevalence of avian influenza A/H5N1 among poultry farmers in rural
      Indonesia, 2007.
AB  - Since 2003, about a third (> 150 cases) of human cases of highly pathogenic avian
      influenza (HPAI) A/H5N1 worldwide are reported from Indonesia. We measured the
      seroprevalence of H5N1 among Indonesian poultry farmers and assessed the risk
      factors for and knowledge of H5N1 infection. In 2007, poultry workers and farm
      residents were interviewed about risk factors for knowledge of and then examined
      for the seropositivity of H5N1 virus. Four hundred ninety-five of 622 farmers
      (80%) from 12 farms participated in the study. Of these, 71% were male, with a
      median age of 29 years. None tested positive for H5N1 virus. Masks were never
      worn by 54% of participants; 86% were afraid of becoming infected. For the
      preceding six months, 1 farm was confirmed as having poultry infected with H5N1
      virus. No evidence of subclinical infection with avian influenza A/H5N1 virus was
      found among poultry farmers, although exposure of the farmers to this virus may
      have been limited. However, we recommend sustaining ongoing surveillance and
      control efforts.

PMID- 21073031
TI  - Responding to pandemic influenza in Cambodia and Lao PDR: challenges in moving
      from strategy to operation.
AB  - Low income countries in Southeast Asia are in a region at risk of emerging
      infectious diseases, notably SARS, H5N1 influenza and H1N1 influenza. Efforts
      have focused largely upon early outbreak response, though with the emergence of
      pandemic influenza, countries in the region are having to prepare to implement
      mitigation measures. We review the challenges for strategy and operation faced by
      two low income countries, Cambodia and Lao People's Democratic Republic (PDR),
      and highlight successes in planing and implementation to date as well as
      identifying needs and challenge that may hinder the future effectiveness of
      control measures.

PMID- 21073032
TI  - Viral respiratory tract infections among patients with acute undifferentiated
      fever in Vietnam.
AB  - To investigate the proportion of viral respiratory tract infections among acute
      undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam
      during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve
      primary health facilities and a clinic for malaria control program. Serum was
      collected on first presentation (t0) and after 3 weeks (t3) for serology. After
      exclusion of acute dengue infection, acute and convalescent serum samples from
      606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM
      and IgG antibodies against common respiratory viruses. Paired sera showed the
      following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus
      (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial
      virus (HRSV, 0.6%). There was no association between type of infection and age,
      sex or seasonality; some inter-annual differences were observed for influenza.
      Antibody prevalence, indicative of previous infections, was relatively low: HPV,
      56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%.

PMID- 21073034
TI  - Social factors related to quality of life among HIV infected children in ubon
      Ratchathani Province, Thailand.
AB  - A cross-sectional study was conducted to determine the social factors and quality
      of life of HIV infected children attending the Pediatric Infectious Disease
      Clinic, Sappasithiprasong Hospital, Ubon Ratchathani Province, Thailand. Data
      were collected during October-November 2008, by interviewing caretakers and their
      children using a structured questionnaire. The children's families were in need
      of improved social support (84.5%), since community resources provided limited
      support, such as clothes, food, financial support, consultation, and information.
      The HIV infected children's quality of life needed improvement (78.7%). The
      factors associated with quality of life included having others as main caretakers
      (OR 4.64, 95% CI 1.45-14.78), parental death (OR 4.19, 95% CI 1.55-11.31), age of
      caregivers above 45 years old (OR 9.52, 95% CI 2.62-34.53), and family income
      less than THB 5,000 per month (OR 5.25, 95% CI 1.14-23.39). However, on
      multivariate analysis, only age of caregiver was a significant predictor for
      quality of life of the child. Children who were cared for by caregivers aged 45
      years or above had a better quality of life than those whose caregivers were 20
      45 years old (OR 6.32, 95% CI 1.12-35.62). Therefore, to improve quality of life
      among HIV infected children, age of caregiver is an important factor to be
      considered. Government and non-government organizations should focus on
      supporting caregivers in terms of food, financial, and emotional support based on
      resources available in the community.

PMID- 21073033
TI  - Screening test accuracy among potential blood donors of HBsAg, anti-HBc and anti
      HCV to detect hepatitis B and C virus infection in rural Cambodia and Vietnam.
AB  - The aim of this study was to determine the accuracy of rapid tests for HBsAg,
      anti-HBc and anti-HCV in rural Cambodia and Vietnam to detect hepatitis B and C.
      In a cross-sectional epidemiological study of two populations of 1,200 potential
      blood donors in rural Cambodia and Vietnam the prevalence rates of HBsAg, anti
      HBc and anti-HCV as established by enzyme immunoassay (EIA) tests were compared
      to rapid test outcomes. The EIA reference test results were validated by
      Architect Chemiluminescent Microparticle Immunoassay (CMIA) technique. The actual
      rapid test demonstrated high specificity for all three test categories as claimed
      by the manufacturer. The test sensitivity observed was significantly lower than
      that claimed by the manufacturer: 86.5% for HBsAg, 86.6% for anti-HBc, and 76.4%
      for anti-HCV. There were large and significant variations in test performance
      between the two countries, especially for HBsAg detection. The low sensitivity of
      the actual rapid tests for HBsAg, anti-HBc and anti-HCV make them useless for
      blood donor screening in rural Southeast Asia. Rapid tests may be useful
      screening tools in blood transfusion services in low-resource settings, but tests
      should be carefully validated locally before being used for screening purposes
      since test performance varies by location.

PMID- 21073035
TI  - Distribution of human rotavirus G and P genotypes in a hospital setting from
      Northern India.
AB  - Rotavirus gastroenteritis is a major cause of severe dehydrating diarrhea in
      children worldwide. Rotavirus G and P genotyping is essential for epidemiological
      surveillance and for better formulation of candidate rotavirus vaccines. Out of
      862 diarrheal stool samples collected from hospitalized children aged < 2 years
      during February 2005 - March 2007, 318 (36.9%) were positive for rotavirus by
      ELISA. G and P genotyping was performed on 100 randomly selected positive samples
      using a seminested multiplex RT-PCR assay. The result of G genotyping indicates
      G1 (60%) was the most predominant VP7 type, followed by G2 (16%), G9 (8%) and G3
      (3%). Two cases of G12 genotype were also observed. P genotypes identified were
      P[8] (40%) followed by P[4] (26%) and P[6] (17%). The most common G-P
      combinations were G1P[8] (26%), followed by G1P[4] and G1P[6]. Mixed infection
      involved 28% of strains. In this study the G1 and P[8] genotypes were the leading
      G and P types. Two cases with G12 genotype were also observed during the study.

PMID- 21073036
TI  - Factors affecting tuberculosis retreatment defaults in Nanded, India.
AB  - This study was carried out to determine factors affecting tuberculosis
      retreatment defaults in Nanded, India. All patients registered as tuberculosis
      retreatment cases (n = 107 excluding deaths during treatment) were interviewed by
      home visits. Their sociodemographic characteristics and treatment history were
      recorded and later compared with their treatment outcomes. Among the patients
      registered for re-treatment of tuberculosis (n = 112), 24 (21.4%) defaulted on
      treatment. The rate of default was 25.8% among those who had previously defaulted
      on treatment. Those who were employed, illiterate and alcoholics were 3.5, 3.5
      and 3.4 times more likely to default, respectively, than others; these
      differences were significant.

PMID- 21073037
TI  - Amino acid sequence of B-cell epitope of N-terminal region of ESAT-6
      Mycobacterium leprae role as specific antigen for diagnosis of leprosy.
AB  - The objective of this study was to find a specific B-cell epitope of N-terminal
      region of antigen L-ESAT-6 from leprosy patients, healthy individuals and healthy
      nurses working for more than 10 years in the leprosy ward of Dr. A. Rivai
      Abdullah Leprosy Hospital, Palembang, Indonesia. Fifty subjects were enrolled in
      this study, comprising 10 subjects with LL type leprosy, 10 subjects with BB type
      leprosy, 10 subjects with TT type leprosy, 10 healthy nurses from leprosy ward
      and 10 healthy individuals as control group. The amino acid sequence of residues
      11-36 of the N-terminal region of L-ESAT-6 were divided into a series of 18
      peptides each consisting of 9-mer peptides with an overlap of 8-mers and an
      offset of one amino acid. The series of 18 peptides were synthesized in the form
      of biotinylated peptides and used to screen sera of 50 subjects using an indirect
      ELISA method. Our study identified at the N-terminal of L-ESAT-6, LEQCQES, VNELQG
      and IDALLE as epitope marker for LL and BB type of leprosy, epitope marker for TT
      type of leprosy and for (protective epitope marker) healthy nurses working for
      more than 10 years in the leprosy ward, respectively. These antigens can be used
      in immunochromatographic test for the early diagnosis of leprosy.

PMID- 21073038
TI  - Role of Burkholderia pseudomallei in the invasion, replication and induction of
      apoptosis in human epithelial cell lines.
AB  - Burkholderia pseudomallei is a bacterial pathogen causing melioidosis. In the
      present study, we demonstrated the effects of B. pseudomallei capsular
      polysaccharide on the invasion, intracellular replication, induction of
      cytotoxicity and apoptosis of human epithelial HeLa and A549 cells. The B.
      pseudomallei capsule mutant had a significantly greater ability to invade both
      cell lines (p < 0.05). The B. pseudomallei capsule mutant had a greater ability
      to induce apoptosis in A549 cells than wild type B. pseudomallei. These results
      indicate the capsular polysaccharide of B. pseudomallei plays an important role
      in inhibiting invasion by the bacteria but has no effect on intracellular
      multiplication, induction of cytotoxicity or apoptosis in epithelial cells.

PMID- 21073039
TI  - Identification and characterization of soil-isolated Streptomyces SJE177
      producing actinomycin.
AB  - One hundred seventy-seven actinomycetes strains were isolated from soils
      collected from fruit orchards in Thailand. All were tested for antibacterial
      activity against seven pathogenic bacteria using co-cultivation methods. Forty
      strains (22.6%) were active against at least one indicator bacteria. Twenty-seven
      strains (15.3%) inhibited only gram-positive bacteria, four strains (2.3%)
      inhibited only gram-negative bacteria, and nine strains (5.1%) showed activity
      against both. Strain SJE177 had potent activity against all tested bacteria, and
      was selected for further investigation. A crude ethyl acetate extract of this
      strain retained inhibitory activity as tested by disk-diffusion method. Analysis
      of morphological and biochemical characteristics and the 16S rRNA gene sequence
      indicated this strain belonged to the genus Streptomyces. The strain formed a
      monophyletic line in a phylogenetic tree of 16S rRNA gene sequences with other
      Streptomyces reference strains. High performance liquid chromatography (HPLC)
      analysis showed SJE177 produced actinomycin. Since many isolates showed
      inhibitory activity against indicator bacteria, these results suggest Thai soil
      could be an interesting source to explore for antibacterial substances.

PMID- 21073040
TI  - Cryptococcocis: a rare fungal infection of the tongue.
AB  - Fungal infection in the oral cavity is not uncommon. The site involved is usually
      species related. Cryptococcus rarely infects the oral cavity. We report an
      elderly patient who presented with a central lesion on the dorsum of the tongue.
      Biopsy revealed a fungal infection. Special stains confirmed cryptococcus. Being
      a rare location for cryptococcal infection, clinical suspicion should be
      correlated with histopathological examination. Once confirmed, the patient should
      be treated with an antifungal medication.

PMID- 21073041
TI  - Knowledge of blood-borne infectious diseases and the practice of universal
      precautions amongst health-care workers in a tertiary hospital in Malaysia.
AB  - This study aimed to assess the knowledge of blood-borne diseases transmitted
      through needle stick injuries amongst health-care workers in a tertiary teaching
      hospital. We also aimed to assess the practices of universal precautions amongst
      these workers and its correlation with the facts. We carried out a cross
      sectional study from January to July 2008 involving various levels of health-care
      workers in Serdang Hospital, Selangor, Malaysia. A self-administered
      questionnaire assessing knowledge of blood-borne diseases and universal
      precautions, and actual practice of universal precautions was used. Two hundred
      fifteen respondents participated in this study; 63.3% were staff nurses. The mean
      knowledge score was 31.84 (SD 4.30) and the mean universal practice score was 9.0
      (SD 2.1). There was a small, positive correlation between knowledge and actual
      practice of universal precautions (r = 0.300, n = 206, p < 0.001) amongst the
      cohort studied. Factors such as age and years of experience did not contribute
      towards acquisition of knowledge about blood-borne illnesses or the practice of
      universal precautions.

PMID- 21073042
TI  - A survey of goiter morbidity in Ban Mae Toen, northwest Thailand.
AB  - A number of cases of goiter have been reported from Ban Mae Toen (BMT)
      northwestern Thailand, therefore we carried out this study to evaluate the
      prevalence and severity of goiter in BMT. We suspected fluoride toxicity as a
      factor in this phenomenon, therefore we used a WHO model using photographs to
      carry out a non-medical survey for teeth discoloration and limb deformity at the
      same time as the goiter survey. Every resident of BMT and a sampled population
      from two nearby control villages were surveyed in 2007. The overall prevalence of
      goiter among both sexes was 11%; 20% in women and 3% in men. No cases of goiter
      were recognised in the two control villages. Twenty-four percent of the BMT
      population and 5% of the sampled population of the control villages had lower
      limb deformities. Sixty-three percent of the BMT population had discoloration of
      teeth, especially among those > 35 years old. The control villages had
      significantly (p < 0.01) fewer cases of discoloration of teeth than the BMT
      population. The morbidity seen in Ban Mae Toen suggests the need for urgent
      enquiry into the etiology of this morbidity.

PMID- 21073043
TI  - Geographical variations in all-cause mortality in Thailand.
AB  - In this study, we examined age-specific death rates among men and women from
      various districts in Thailand using mortality data from 1999 to 2001. A Poisson
      generalized linear model was used for analysis. To adjust for large variations in
      resident populations among districts, the 926 districts in Thailand were reduced
      to 235 "superdistricts" based on a minimum population of 200,000. The Poisson
      model incorporating additive factors for age-group and superdistrict generally
      provided a good fit for these data. The fitted mortality rates among the 235
      superdistricts were compared with the overall means for each gender (637 per
      100,000 for males and 415 per 100,000 for females). Thematic maps were created
      with three different colors signifying each superdistrict's mortality rate
      compared to the mean. Northeastern Thailand had higher than average mortality for
      both males and females. Lower than average death rates were found in southern
      Thailand with the exception of Phuket and Narathiwat, and in Bangkok, except for
      females in the superdistrict containing Nong Chok and Lat Krabang Districts. This
      modeling and mapping approach is a useful preliminary tool enabling public health
      planners to determine statistically valid geographical variations in mortality
      and to develop effective interventions.

PMID- 21073044
TI  - Review of injuries over a one year period among 87,134 adults studying at an open
      university in Thailand.
AB  - Countries need epidemiological information about population injury statistics to
      devise preventive strategies. To generate such information we estimated the one
      year incidence and distribution of injury in a group of 87,134 adult Sukhothai
      Thammathirat Open University distance-learning students residing throughout
      Thailand. Those who participated joined the study by filling out a baseline
      questionnaire in 2005 which included a one-year recall of injuries serious enough
      to interfere with daily activities and/or require medical treatment. The more
      serious injuries were categorised by location, mechanism and intentionality. We
      collected sociodemographic information about the participants. Nearly 22% of
      participants reported at least one injury during the previous 12 months. Males,
      those with lower income and the less educated, had higher injury rates. Home
      injuries were more common among females. Sports, road and workplace injuries were
      more common among males. Transport injuries decreased with age and falls
      increased with age. Most injuries were unintentional. Injury rates among Thai
      adults are high. We identified at risk groups by injury mechanism and setting.
      Before interventions can be devised more research is needed regarding exposure
      and vulnerability in at risk socio-demographic groups.

PMID- 21073045
TI  - Paraoxonase 1 activity as a predictor of cardiovascular disease in type 2
      diabetes.
AB  - The role of paraoxonase 1 in cardiovascular disease complications in type 2
      diabetes mellitus is not fully understood. We studied paraoxonase activity
      towards paraoxon in 188 non-diabetic and 140 diabetic subjects using general
      linear models and univariate analysis. Adjusting for age revealed a reduction in
      activity towards paraoxon was associated with a significant increase in risk (p =
      0.023) for cardiovascular disease complications in diabetic patients.
      Multivariate analysis of two plasma measures of paraoxonase activity using
      paraoxon and diazoxon also showed reduced paraoxonase activity towards paraoxon
      was associated with a significant increase in risk (p = 0.045) for cardiovascular
      disease complications in diabetic patients. These analyses showed that a reduced
      paraoxonase activity towards paraoxon was associated with ethnicity. Based on
      multivariate analysis, subjects of Malay ethnic origin have significantly higher
      than expected activity (p = 0.008, compared to Indians), towards paraoxon than
      subjects of Chinese origin who in turn had higher than expected paraoxonase
      activity (p = 0.028, compared to Indians) Indian subjects.

PMID- 21073046
TI  - Hemoglobin variants in patients with type 2 diabetes mellitus.
AB  - Measurement of HbA1c levels in diabetic patients is an established procedure for
      evaluating long-term control of diabetes. Despite its usefulness, conditions that
      effect hemoglobin concentration, such as hemoglobinopathies give rise to
      inappropriate HbA1c values. Since information about hemoglobinopathies in the
      diabetic population in Sri Lanka is limited, a prospective cross-sectional study
      was carried out among 2,695 diabetic subjects attending the diabetic clinic at
      Nawaloka Hospital, Sri Lanka. Hemoglobin type and HbA1c were measured by the HPLC
      method. The results reveal among 2,695 diabetic subjects, 53 (2%) had abnormal
      hemoglobin types (HbF and HbS). HbA1c concentrations in diabetic patients without
      Hb abnormalities show a higher correlation with fasting blood glucose than those
      with hemoglobin abnormalities. This study emphasizes that patients with
      inappropriate HbA1c values should be investigated for hemoglobinopathies.

PMID- 21073047
TI  - Cotinine levels in serum and bronchoalveolar lavage fluid.
AB  - Cotinine is a major metabolite of nicotine. This study was planned to investigate
      the relationship between bronchoalveolar lavage (BAL) fluid cotinine levels and
      serum cotinine levels in smokers and nonsmokers with various pulmonary diseases
      and to investigate whether these levels are affected by passive smoking. Serum
      and BAL fluid cotinine levels were measured in 27 patients. BAL cotinine levels
      were measured using a sensitive ELISA kit produced to measure cotinine in saliva.
      Plates were read by microuant (BioTek, USA) micro plate reader. All patient serum
      cotinine levels were detectable except for one nonsmoker patient. However, BAL
      fluid cotinine levels were measurable in only 6 patients (two of them were
      nonsmokers). A significant positive correlation was seen between serum and BAL
      fluid cotinine levels (r = 0.726; p = 0.000). Serum cotinine levels were
      significantly higher in present smokers than non-smokers (21.0 +/- 16.01; 5.35 +/
      7.65; p = 0.004). However, there were no significant differences in BAL fluid
      cotinine levels between smokers and nonsmokers. Passive smoking can increase
      nicotine metabolites in serum and other body fluids, including BAL fluid. Since
      BAL fluid and serum cotinine levels were well correlated, there is no need to use
      invasive procedures, such as bronchoscopy and expensive, time consuming BAL fluid
      analyses. Serum cotinine levels can give a rough idea of smoking status. BAL
      fluid cotinine meaurements should be done for only scientific reasons.

PMID- 21073048
TI  - Attitudes towards a smoking ban in restaurants of managers, employees and
      customers in Kunming City, China.
AB  - The objective of this study was to investigate the attitudes of restaurant
      managers, employees and customers towards a total smoking ban policy in
      restaurants. A restaurant based survey in an urban area of Kunming City, China,
      was carried out from May to August 2009. One hundred managers, 1,055 employees
      and 5,213 customers aged 15 years or above were interviewed using a structured
      questionnaire. The percentage of respondents supporting a total smoking ban in
      restaurants was 17% among managers, 13.4% among employees, and 16.6% among
      customers. Multilevel analysis confirmed respondents who did not smoke, who were
      educated, and who worked or dined at a restaurant with fewer than 200 seats were
      more likely to support a total smoking ban. A total smoking ban in restaurants is
      unlikely to be supported by people involved in the restaurant business in the
      study area. This coincides with poor awareness of the harms of smoking.

PMID- 21073049
TI  - Cruveilhier-Baumgarten syndrome in a cirrhotic patient taking alcohol with
      Boesenbergia pundurata.
AB  - Cruveilhier-Baumgarten syndrome (CBS) is a rare complication of cirrhosis. We
      reported a case of CBS who came to hospital with progressive ascites, jaundice,
      fever and upper gastrointestinal bleeding. The cause of cirrhosis and hepatitis
      might be due to alcohol and possibly local Thai herb [Boesenbergia pundurata
      (Roxb.) Schitr or Krachaidum].

PMID- 21073050
TI  - Optimizing the culture of Plasmodium falciparum in hollow fiber bioreactors.
AB  - The hollow fiber bioreactor (HFBR) is a cell culturing system allowing continuous
      perfusion of medium. It was designed to grow microorganisms in a dynamically
      altering medium mimicking change in the in vivo intravascular and extravascular
      compartments. The cell compartment (extra capillary space) and medium compartment
      (intra capillary space) are connected through pores of semipermeable fiber
      membranes. These membranes allow exchange of gas and nutrients. We have adapted
      this system for the ex vivo culture of Plasmodiumfalciparum at high parasite
      densities. A Thai P. falciparum isolate (TM036) cultured in RPMI, supplemented
      with 0.5% Albumax II, could be maintained continuously in the system by daily
      changes of a small volumes of medium. Under optimized conditions the HFBR
      cultures attained 8% parasitemia in 40% hematocrit, thereby providing a total
      parasite biomass of 6.0 x 10(9) parasitized erythrocytes. The main problem
      encountered was clogging of micropores in the hollow fiber system by cellular
      debris over time. Although 'reverse flushing' partly prevented this, a larger
      pore size might be needed to overcome this problem. The system opens new
      possibilities for the study of in vitro drug sensitivity under conditions
      mimicking in vivo pharmacokinetics, and the selection of anti-malarial drug
      resistance and associated parasite biological and genomic changes.

PMID- 21073051
TI  - Prevalence and genotyping of Cryptosporidium SPP from dairy cow fecal samples in
      western Thailand.
AB  - The aims of this study were to determine the prevalence of Cryptosporidium spp in
      dairy cows in central Thailand and to investigate the genotype of Cryptosporidium
      spp in this population. A total of 200 fecal samples from dairy cows were
      collected and examined by the acid-fast staining technique and polymerase chain
      reaction restriction fragment length polymorphism (PCR-RFLP). The prevalence of
      Cryptosporidium infection in dairy cows was 7% (95% CI 3.5-10.5) by acid-fast
      staining, and 15.5% (95% CI 10.5-20.5) by PCR-RFLP. This is the first report of
      genetic identification of the C. parvum bovine genotype in dairy cows in
      Thailand. PCR-RFLP analysis showed all positive samples were C. parvum (bovine
      genotype). C. andersoni was not found in this study. The only significant risk
      factor for Cryptosporidium infection in dairy cows was age. Calves less than 2
      months old were more frequently infected by Cryptosporidium than others (OR
      13.82, 95% CI 3.67-51.97, p = 0.001). Cattle may be a potential source of human
      cryptosporidiosis.

PMID- 21073052
TI  - Comparison of Pouzolzia indica methanolic extract and Virkon against cysts of
      Acanthamoeba spp.
AB  - The present study was conducted to investigate the morphological and structural
      changes of Acanthamoeba cysts after being treated with various concentrations of
      Pouzolzia indica methanolic extract fraction 3 (methanol eluted) and Virkon
      solution. Changes in the Acanthamoeba cysts were detected by light microscopy,
      scanning electron microscopy and transmission electron microscopy. The results
      show Acanthamoeba cysts were killed by Pouzolzia indica methanolic extract
      fraction 3 at a concentration of 1:8 and by Virkon solution at a concentration of
      0.25%, with a minimal cysticidal concentration (MCC) by 24 hours. Both agents
      caused similar structural damage to Acanthamoeba cysts in the same sequence. Step
      by step structural alterations occurred within the cyst. First, the cyst shrank,
      collapsed and had clumping of cytoplasmic stuctures inside the cyst walls.
      Second, the cysts began to bulge, swell, have a decrease in wrinkles in the cyst
      walls and spill the cytoplasmic contents into the environment. Finally, the cyst
      walls broke into small pieces. This study may be beneficial to compare with
      future studies of pharmaceutical agents against Acanthamoeba keratitis.

PMID- 21073053
TI  - Application of recombinant SMR-domain containing protein of angiostrongylus
      cantonensis in immunoblot diagnosis of human angiostrongyliasis.
AB  - The aim of this study was to find novel proteins expressed from an
      Angiostrongylus cantonensis adult female worm cDNA library for serodiagnosis of
      angiostrongyliasis. An immuno-dominant clone, fAC22, was identified by
      immunoscreening with pooled positive sera from proven angiostrongyliasis
      patients. The clone contained an open reading frame of 2,136 bp encoding a 80.5
      kDa protein with a predicted isoelectric point of 5.8. The deduced amino acid
      sequence (712 amino acids) contained the conserved domain of Small mutS related
      (Smr) superfamily protein, with similarity with the Smr domain protein of Brugia
      malayi. The fusion His-tagged 81 kDa recombinant protein expressed as inclusion
      body in Escherichia coli was solubilized and purified by Ni-affinity
      chromatography for use in immunoblot analysis. Its sensitivity, specificity,
      positive and negative predictive values in immunodiagnostic test was 93.5, 91.5,
      79.0 and 97.5%, respectively. Although some cross-reactivity of the antigen was
      observed among gnathostomiasis, bancroftian filariasis, ascariasis,
      echinococcosis, paragonimiasis and opisthorchiasis, sera from 14 other infections
      were all negative. These data indicate its possible application in
      immunodiagnosis of clinically suspected angiostrongyliasis. Key words:
      Angiostrongylus cantonensis,eosinophilic meningitis, recombinant fusion protein,
      immunodiagnosis

PMID- 21073054
TI  - A single dose of doxycycline in combination with diethylcarbamazine for treatment
      of bancroftian filariasis.
AB  - Standard treatment of lymphatic filariasis with diethylcarbamazine (DEC) is
      associated with systemic adverse reactions, thought to be due to the release of
      microfilariae material and Wolbachia endosymbiotic bacteria into the blood.
      Combination treatments with doxycycline for 3-8 weeks are more effective than
      standard treatment. However, long-term use of antibiotics may contribute to drug
      resistance and are not practical for use in remote areas. We assessed whether a
      single dose of doxycycline combined with the standard DEC regimen would reduce
      the incidence and severity of adverse reactions and increase the efficacy of
      standard treatment. Forty-four subjects from Tak Province were recruited into the
      randomized double-blind clinical trial study: 25 received DEC (300 mg) combined
      with a placebo, and 19 received DEC (300 mg) combined with doxycycline (200 mg).
      The incidences of adverse reactions to standard treatment were lower in the
      doxycycline group (45.5%) than in the placebo group (58.8%). Severe reactions
      occurred only in the placebo group (3 of 25 subjects). The severity of adverse
      reactions was significantly lower in the doxycycline group (mean score 0.45) than
      in the placebo group (mean score 1.17). The levels of IL-6 and Wolbachia DNA in
      the plasma were significantly lower in the doxycycline group. The filarial
      antigen levels were significantly lower in the doxycycline group at months 6
      after treatment.

PMID- 21073055
TI  - Iso-electricfocusing of Bithynia snail antigens for IgG- and IgG(1-4)-ELISA
      detection of human opisthorchiasis.
AB  - Diagnosis of opisthorchiasis is confirmed by the presence of characteristic eggs
      and worms. However, misdiagnosis may occur in light infections, and also due to
      the morphological similarity of opisthorchid eggs to other species. A finding of
      specific immune mediators can help confirm infection. This study used indirect
      ELISA to detect total IgG and IgG(1-4) with selected antigens of Bithynia
      siamensis goniomphalos extract, which were derived by liquid-phase iso
      electricfocusing (IFE). Antigens (Iso-AgF) from 20 IEF fractionated fractions
      were selected based on a high ELISA-OD ratio between pooled-positive and pooled
      negative sera. Iso-AgF 7, 7, 6, 2, and 10 resulted in high OD-ratio to total IgG,
      IgG1, 2, 3, and 4, respectively. A full-scale ELISA was conducted with sera from
      50 opisthorchiasis cases, 196 from other parasitic-disease cases, and 35 healthy
      controls. Iso-AgF7 to IgG1 showed the best result, with sensitivity, specificity,
      positive and negative predictive value of 100, 96, 86, and 100%, respectively, at
      a cut-off 0.221. Low cross-reactivity to IgG1 was found in one case each of
      gnathostomiasis, trichinellosis, toxocariasis, angiostrongyliasis, bancroftian
      filariasis, enterobiasis, neurocysticercosis, and taeniasis. Thus, Iso-AgF7 to
      IgG1 was a good candidate antigen to be developed for detection of antibodies
      against Opisthorchis viverrini.

PMID- 21073056
TI  - Habitat characterization and mapping of Anopheles maculatus (Theobald) mosquito
      larvae in malaria endemic areas in Kuala Lipis, Pahang, Malaysia.
AB  - In Peninsular Malaysia, a large proportion of malaria cases occur in the central
      mountainous and forested parts of the country. As part of a study to assess
      remote sensing data as a tool for vector mapping, we conducted entomological
      surveys to determine the type of mosquitoes, their characteristics and the
      abundance of habitats of the vector Anopheles maculatus in malaria endemic areas
      in Pos Senderot. An. maculatus mosquitoes were collected from 49 breeding sites
      in Pos Senderot. An. maculatus preferred to breed in water pockets formed on the
      bank of rivers and waterfalls. The most common larval habitats were shallow pools
      5.0-15.0 cm deep with clear water, mud substrate and plants or floatage. The
      mosquito also preferred open or partially shaded habitats. Breeding habitats were
      generally located at 100-400 m from the nearest human settlement. Changes in
      breeding characteristics were also observed. Instead of breeding in slow flowing
      streams, most larvae bred in small water pockets along the river margin.

PMID- 21073057
TI  - Insect repellent activity of medicinal plant oils against Aedes aegypti (Linn.),
      Anopheles minimus (Theobald) and Culex quinquefasciatus Say based on protection
      time and biting rate.
AB  - This study investigated insect bite protection and length of the protection with
      30 repellents which were divided into 3 categories: plant oil, essential oil and
      essential oil with ethyl alcohol, tested against three mosquito species, Aedes
      aegypti, Anopheles minimus and Culex quinquefasciatus, under laboratory
      conditions. The plant oil group was comprised of Phlai (Zingiber cassumunar) and
      Sweet basil (Ocimum basilicum). Both substances were effective as repellents and
      feeding deterrents against An. minimus (205 minutes protection time and a biting
      rate of 0.9%), Cx. quinquefasciatus (165 minutes protection time and 0.9% biting
      rate) and Ae. aegypti (90 minutes protection time and 0.8% biting rate).
      Essential oil from citronella grass (Cymbopogon nardus) exhibited protection
      against biting from all 3 mosquito species: for An. minimus, Cx. quinquefasciatus
      and Ae. aegypti, the results were 130 minutes and 0.9%, 140 minutes and 0.8%, and
      115 minutes and 0.8%, respectively. The period of protection time against Ae.
      aegypti for all repellent candidates tested was lower than the Thai Industrial
      Standards Institute (TISI) determined time of greater than 2 hours.

PMID- 21073058
TI  - Geo-database use to promote dengue infection prevention and control.
AB  - Dengue infection (DI) is a major health problem in Thailand and is especially
      prevalent in Ubon Ratchathani Province. The objectives of the project were: (1)
      to develop a geo-database system for DI prevention and control, (2) to perform an
      Aedes aegypti larval vector survey for DI prevention and control in Ubon
      Ratchathani Province, (3) to study the behavior and perceptions regarding DI
      prevention among the target population in Ubon Ratchathani Province. Ten villages
      with high incidences of DI over a 3 year period from 2005 to 2007 were selected.
      The survey was divided into 2 periods, pre-outbreak period (February-April 2008)
      and outbreak period (June-August 2008). The data were collected in April and June
      2008. The households in each village were purposively sampled. Water containers
      inside and outside of the houses were surveyed using the World Health
      Organization's house index (HI), container index (CI), and Breteau index (BI).
      The location of each household was recorded using the global positioning system
      (GPS). Data regarding people's perceptions and behaviors concerning DI prevention
      were collected during interviews of 383 families in Mach 2008. A database for DI
      was developed using ArcView version 9.2. The results showed during the pre
      outbreak period, Non Jig, Non Sawang, and Huai Teeneu villages had the highest
      risk level (BI > or =50). During the outbreak period, Non Jig and Huai Teeneu
      village had the highest risk level (BI > or =50). Results regarding DI
      perceptions showed the target population had high levels of DI perceptions. DI
      preventive behavior was found in 50.9%.

PMID- 21073059
TI  - The impact of a program for strengthening dengue hemorrhagic fever case
      management on the clinical outcome of dengue hemorrhagic fever patients.
AB  - This study compared the case fatality ratio (CFR) of dengue shock syndrome (DSS)
      patients admitted to Buri Ram Hospital, an area with CFR of 0.11, 0.43 and 0.23%
      in 2002, 2003 and 2004, respectively, to obtain a provincial model for dengue
      case management using the I. development of a special program for strengthening
      dengue hemorrhagic fever (DHF) case management (No deaths in DSS patients), II. a
      retrospective review of the medical records of dengue fever (DF), DHF and DSS
      patients referred to Buri Ram Hospital. We compared the data during the 3 periods
      of the implementation of this program. Data was statistically analyzed using chi2
      or Fisher's exact test for categorical variables, one-way ANOVA for continuous
      data with normal distribution and Kruskal-Wallis test for nonparametric
      variables. The numbers of DF, DHF and DSS cases in Buri Ram were 1332, 1700 and
      1630 person, respectively, during 2006-2008. The number of DSS patients increased
      after implementation of the program: 12.2, 51.2 and 47.22 for 2006, 2007 and
      2008, respectively, but the complications of the disease decreased. The CFR
      during 2006, 2007 and 2008 were 0.15, 0 and 0.06% (p > 0.05). The program for
      strengthening DHF case management did improve clinical outcomes in dengue
      patients after the implementation. The CFR in 2008 was only 0.06%, lower than the
      goal of the Ministry of Public Health (<0.13%). This program is still running,
      sustaining low CFR in dengue patients. It may be used as a model for other
      provinces in Thailand that have high dengue deaths.

PMID- 21073060
TI  - Dengue hemorrhagic fever presenting with acute pancreatitis.
AB  - Acute pancreatitis is an uncommon manifestation of dengue fever. Here we present
      a 47 year old male with dengue hemorrhagic fever who presented with acute
      pancreatitis and associated hyperglycemia. To our knowledge, this is the first
      reported case of dengue complicated with acute pancreatitis from South Asia.

PMID- 21073061
TI  - Intrahepatic HBV DNA and covalently closed circular DNA (cccDNA) levels in
      patients positive for anti-HBc and negative for HBsAg.
AB  - Covalently closed circular DNA (cccDNA) is a unique episomal replicative
      intermediate molecule of hepatitis B virus (HBV) which plays a key role in viral
      persistence. The aim of this study was to prove cccDNA persistence in the liver
      tissue of patients negative for hepatitis B surface antigen (HBsAg) and positive
      for antibody to hepatitis core antigen (anti-HBc). Intrahepatic HBV DNA and
      cccDNA were determined using real-time and semi-nested PCR assays on the liver
      tissues of 35 patients who were negative for HBsAg and positive for anti-HBc with
      or without anti-HBs. HBV DNA was detected in the liver tissue of 4 out of 35
      patients who were positive for anti-HBc. None of the samples harbored cccDNA. In
      this study population, which is of Asian origin, very low levels of HBV DNA were
      detected in a small percentage of patients with anti-HBc. Even using the highly
      sensitive semi-nested PCR assay, HBV cccDNA was not detectable in any anti-HBc
      positive patients either with or without anti-HBs.

PMID- 21073063
TI  - The private demand for Hib vaccination in a probable low Hib disease incidence
      country: Thailand 2006.
AB  - This study aimed to determine the private demand for Hib vaccination in Thailand.
      A willingness-to-pay (WTP) survey was performed by face-to-face interviews of 662
      pregnant women attending antenatal clinics in 4 regions of the country.
      Hypothetical incidence scenarios of Hib disease and hypothetical vaccine market
      scenarios were presented to the respondents. Regarding the scenarios, the
      respondents responded to discrete choice questions asking for their WTP for Hib
      vaccination for their children. Probit regression models were used to predict
      median WTP for Hib vaccine per child. A median WTP for Hib vaccine per child per
      vaccination course was estimated at THB 3800, or USD 106. Although Hib disease
      incidence in Thailand is probably low, high monetary value of WTP for Hib vaccine
      probably reflects concern among Thai people about severity of the disease and
      good perceptions about safety and efficacy of the vaccine.

PMID- 21073062
TI  - Immunogenicity of HBV vaccine during stated shelf-life.
AB  - Thiomersal has been used as preservative in multi-dose vials of hepatitis B
      vaccine (Engerix-B). Due to safety concerns, thiomersal was replaced with 2
      phenoxyethanol (2PE) as preservative in multi-dose vials. The potency of 2PE
      preserved hepatitis B vaccine multiple use vials was measured over the shelf-life
      in terms of immunogenicity, reactogenicity and safety. This single-blind,
      randomized study was conducted with the assistance of employees of
      GlaxoSmithKline Biologicals, makers of the Engerix-B vaccine. Four hundred twenty
      subjects aged > or =18 years were randomized to receive three doses (0, 1, 6
      months) of 2PE preserved hepatitis B vaccine kept on the shelf <12 months (2PE
      New group), 2PE preserved hepatitis B vaccine kept on the shelf >18 months (2PE
      Old group), or thiomersal preserved hepatitis B vaccine [HBV(Thio) group]. Anti
      HBs was measured by GlaxoSmithKline Biologicals post-vaccination; the
      reactogenicity and safety of the vaccines were assessed. Protective anti-HBs
      levels (> or =10 mIU/ml) were measured one month after dose 3. The results showed
      protective levels in 86.8% (2PE New), 89% (2PE Old) and 95.3% [HBV(Thio)]. There
      was no difference detected between the 2PE New and 2PE Old groups in terms of
      anti-HBs seroprotection rates and geometric mean concentrations one month after
      dose 3. However, both 2PE groups had significantly lower seroprotection rates
      than the HBV(Thio) group and the number of non-responders was higher in the 2PE
      groups than in the Thio group. A antibody response rates over time were similar
      between the 2PE New and Old groups. The reactogenicity profiles were acceptable
      and the ranges were similar for each group. The shelf-life of the vaccines had no
      impact on immunogenicity or reactogenicity and 2PE preserved hepatitis B vaccine
      can be considered stable over time.

PMID- 21073064
TI  - A butterfly shaped alveolar hemorrhage caused by cytomegalovirus.
AB  - Abstract. We report here a 35 year-old immunocompetent male, with a fulminantly
      lethal diffuse alveolar hemorrhage caused by CMV pneumonia. The patient was
      admitted with fever, rust colored sputum and exertional dyspnea. A chest x-ray
      revealed bilateral alveolar infiltration in a butterfly pattern. Bronchoalveolar
      lavage (BAL) was performed which revealed alveolar hemorrhage. Microscopic
      findings of the lavage fluid revealed large numbers of erythrocytes and
      hemosiderin-laden macrophages. The patient did not improve with empiric
      antibiotic treatment. High CMV IgG and IgM titers were found in the serum. The
      patient died from respiratory failure after detection of inclusion bodies on BAL
      before initiation of antiviral therapy.

PMID- 21073065
TI  - Antibiosis of Burkholderia ubonensis againist Burkholderia pseudomallei, the
      causative agent for melioidosis.
AB  - Melioidosis, caused by Burkholderia pseudomallei, is an enigmatic infectious
      disease that afflicts individuals in many tropical and developing regions.
      Treatment is hampered by the organism's innate antibiotic resistance and the
      disease's non-pathognomic presentation. Recently, added attention has been given
      to this organism due to its classification as a potential biowarfare agent.
      Therefore, methods of preventing acquisition of infection are needed. We
      investigated antagonism between Burkholderia spp and B. pseudomallei derived from
      the same ecological niche in a melioidosis endemic region in Papua New Guinea.
      Isolates of environmentally derived non-pseudomallei Burkholderia spp (n=16) were
      screened for antibiosis against 27 B. pseudomallei isolates. Three isolates
      subsequently identified as B. ubonensis produced specific antagonistic activity
      against all B. pseudomallei isolates tested. The antagonistic compound in a cell
      free state was obtained from a representative producing strain, with subsequent
      biological characterization revealing a pepsin sensitive peptide moiety
      consistent with a bacteriocin-like compound. To our knowledge, this is the first
      report of antagonistic activity demonstrated by near-neighbor Burkholderia
      against B. pseudomallei. This antagonism may be important in the micro-ecology of
      B. pseudomallei, and could also have application in the biocontrol of this
      pathogen.

PMID- 21073066
TI  - Status of Vi gene, its expression and Salmonella Pathogenicity Island (SPI-7) in
      Salmonella Typhi in India.
AB  - Salmonella enterica serotype Typhi (S. Typhi) is a causative organism of typhoid
      fever. A number of Salmonella serovars express a capsular polysaccharide antigen
      known as Vi, the biosynthetic and export proteins of which are encoded within the
      viaB locus of Salmonella Pathogenicity Island -7 (SPI-7). SPI-7 is inserted
      between two partially duplicated copies of tRNA -pheU gene. We have investigated
      the frequency of viaB operon deletion and loss of SPI-7 due to storage of strains
      collected during the period 1987-2006 by PCR amplification of fliC (for
      confirmation of serotype Typhi), tviB (for status of viaB operon) and tRNA -pheU
      (for absence of SPI-7). All 111 isolates were observed with positive
      amplification of 495 bp amplicon for fliC. A total of 36 isolates were negative
      for Vi by agglutination while 39 were negative for viaB operon. Interestingly,
      106 isolates were found to have SPI-7. The 5 SPI-7 negative isolates were
      isolated during recent years. Long-term storage and repeated culture had little
      or no effect on SPI-7, as none of the 18 isolates recovered from blood before
      1997 lacked SPI-7. On the other hand, loss of viaB operon was directly
      proportional to duration of storage. Thus, it is proposed that stability of Vi
      gene is dependent on the presence of selection pressure.

PMID- 21073067
TI  - Preliminary report of SCCmec-types and antimicrobial susceptibilities of
      methicillin-resistant Staphylococcus aureus isolates from a university hospital
      in Thailand.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has spread worldwide. It is a
      major cause of hospital-acquired infections in most hospitals for nearly half
      century. The present study was conducted to examine the antimicrobial
      susceptibilities and staphylococcal cassette chromosome mec (SCCmec)-type for
      MRSA isolates from 237 patients treated at Srinagarind Hospital between September
      2002 and August 2003. Antimicrobial susceptibility testing for all isolates was
      performed using an agar dilution method and SCCmec-types of 81 representatives
      from 237 isolates were determined using multiplex PCR. The minimum inhibitory
      concentration (MIC) ranges for the MRSA isolates were as follows: cefazolin 8 to
      > or =64; erythromycin < or = 0.5 to > or =64; gentamicin < or = 0.5 to > or =64;
      imipenem < or = 0.5 to >16; ofloxacin < or = 0.5 to > or =64; oxacillin 16 to >
      or =64; tetracycline 2 to > or =64 and vancomycin < or = 0.5 to 2 microg/ml. All
      MRSA isolates were susceptible to vancomycin, but only 0.4% to 8.9% was
      susceptible to the remaining antimicrobial agents. Of the 81 isolates tested, 2
      types of SCCmec were found (76 with type III and 2 with type II) and no mecA gene
      was detected in 3 isolates. Sixty-seven of the 78 isolates carried the mercury
      resistant operon. The multilocus sequence type in isolates with type III SCCmec
      was ST239 and in isolates with type II SCCmec was ST5.

PMID- 21073068
TI  - Rhinofacial entomophthoramycosis; a case series and review of the literature.
AB  - Rhinofacial entomophthoramycosis is an uncommon chronic mycotic disease caused by
      exposure to the organism Conidiobolus coronatus. The authors report a case series
      of 5 patients with rhinofacial entomophthoramycosis and review the literature.
      All patients had typical involvement of the rhinofacial area with formation of
      subcutaneous lesions causing a chronic granulomatous inflammatory response with
      tissue eosinophilia and Splendore-Hoeppli reaction. Diagnoses were made based on
      histopathologic examination in all cases and fungi were isolated and identified
      in one case. The clinicopathologic features and therapeutic management of
      rhinofacial entomophthoramycosis are described.

PMID- 21073069
TI  - Prevalence of non-alcoholic fatty liver in a hypercholesterolemic population of
      northwestern peninsular Malaysia.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease
      worldwide and a frequent finding on ultrasound examination. NAFLD is considered
      as the liver component of metabolic syndrome and is linked to accelerated
      atherosclerosis and cardiovascular disease. No data from systematic studies
      regarding the prevalence of NAFLD are available for the Malaysian population. One
      hundred eighty untreated hypercholesterolemic volunteers underwent blood and
      ultrasound examinations to evaluate their livers. NAFLD was diagnosed in 102
      subjects (56.7%) with similar prevalences between sexes. Of the 102 positive
      subjects 82 (80.4%) were graded as mild, 17 (16.7%) as moderate and 3 (2.9%) as
      severe fatty liver cases. Elevated fasting plasma glucose (FPG) levels were found
      in 13 of 180 subjects (7.2%), while elevated AST and ALT levels were seen in 30
      (16.7%) and 22 (12.2%) of the180 subjects, respectively.

PMID- 21073070
TI  - Self-efficacy, self-care behaviors and glycemic control among type-2 diabetes
      patients attending two private clinics in Yangon, Myanmar.
AB  - This cross-sectional study aimed to estimate the prevalence of glycemic control
      and its associated factors among type-2 diabetes patients attending two private
      clinics in Yangon, Myanmar. Two hundred sixty-six diabetes patients attending two
      private diabetes clinics in Yangon during February and March, 2009 were included
      in the study. The participants completed a structured questionnaire. HbA(1c) was
      used as the index for glycemic control. The prevalence of successful glycemic
      control (HbA(1c) < or =7%) was 27.1%. The median HbA(1c) value was 7.8%. About
      62.0% of patients had high self-efficacy levels, and 30.8% had good self-care
      behavior. Multiple logistic regression analysis revealed four variables
      associated with glycemic control: age > or =60 years (OR 2.46, 95% CI 1.17-5.21),
      taking one oral hypoglycemic agent (OHA) (OR 2.56, 95% CI 1.26-5.19), being
      overweight (OR 2.01, 95% CI 1.02-3.95) and having a high self-efficacy level (OR
      5.29, 95% CI 2.20-12.75). Interventions to increase diabetic patient self
      efficacy levels and self-care behavior, especially related to diet and exercise,
      are needed to reduce poor glycemic control.

PMID- 21073071
TI  - HIV/AIDS-related knowledge, attitudes and perceptions: a cross-sectional
      household survey.
AB  - This study aimed to assess knowledge of and attitudes toward HIV/AIDS among a
      community in a semi-urban setting in Malaysia, to determine factors affecting
      perceptions toward people living with HIV in the community, and to provide
      baseline information for planning preventive measures against HIV/AIDS. This
      cross-sectional study was conducted in August 2009. Two hundred sixty-two
      household members were interviewed with a semi-structured questionnaire. Most
      respondents (232; 88.5%) had heard of HIV/AIDS. Only a few respondents (6; 2.6%)
      could correctly answer all the questionnaire items. Misconceptions about disease
      transmission were seen among surveyed participants, such as the belief HIV/AIDS
      can be contracted from saliva (104; 44.8%), mosquito bites (95; 40.9%) or casual
      touch (86; 37.1%). A multivariate linear regression model showed better
      perceptions towards people living with HIV depend on an improved knowledge of
      HIV/AIDS transmission. Current data emphasize the need to scale up HIV/AIDS
      education incorporating the mode of disease transmission.

PMID- 21073072
TI  - Development of a model for parent-adolescent daughter communication about
      sexuality.
AB  - This study aimed to develop a model for parent-adolescent daughter communication
      about sexuality (PDCS). The subjects were 18 mother-doughter pairs. The females
      were 12-13 years old studying in the 7th grade of a secondary school in Bangkok.
      The model had 3 parts: (1) the process of PDCS development, (2) the essential
      components, characteristics and patterns of PDCS and (3) the impact of the
      program. The model was examined using both quantitative (paired t-test) and
      qualitative (content analysis) methods. The inputs, assessing the guardian and
      adolescent female factors, included sexuality knowledge, understanding of the
      daughter's sexual development, attitudes regarding talking about sexuality,
      perceptions regarding communication and the maternal-daughter relationship, and
      uncomfortable feelings and confidence in ability to talk about sexuality. The
      processes included: (1) raising awareness and enhancing positive attitudes about
      PDCS, (2) establishing sexual knowledge and development, (3) establishing a
      maternal-daughter relationship and (4) training in reciprocal PDCS skills. The
      output was modification of maternal and daughter communication skills that
      occurred during the shared discussion and reflection process. The outcomes
      reflected 4 aspects: feelings toward PDCS, characteristics of PDCS, sexual
      knowledge, and maternal-daughter relationship. The model was successful in
      guardian implementation and networking were established on their own with the
      cooperation of both subjects in accordance with their likenesses, abilities, and
      competencies. There was little assistance needed from the researcher or teacher
      to support self reliance with the PDCS.

PMID- 21073073
TI  - Blood pressure control among diabetic hypertensives under cardiology follow-up at
      a regional hospital in rural Malaysia.
AB  - Three hundred thirty-one consecutive patients presenting with hypertension to the
      outpatient medical clinic of Tengku Ampuan Afzan Hospital, Kuantan, Malaysia were
      screened and 150 patients with concurrent diabetes were enrolled into a cross
      sectional study. The majority of patients were male (60.6%) with a mean age of
      60.0 +/- 11.0 years. The mean systolic blood pressure (SBP) was 140.9 +/- 20.1
      mmHg and the mean diastolic blood pressure (DBP) was 81.7 +/- 9.8 mmHg. Only
      38.0% (57/150) of patients had blood pressures within recommended guidelines
      (130/80 mmHg). The mean blood pressure in this group was 123.7 +/- 8.5/76.4 +/-
      5.6 mmHg. The majority of patients were on either 2 (41.3%) or 3 (31.3%) anti
      hypertensives. Females had a significantly higher SBP 145.4 +/- 22.7 vs. 138.0 +/
      17.8 mmHg in males (p = 0.026). The level of blood pressure control in diabetics
      was unsatisfactory, especially in females and the elderly. A reassessment of
      priorities in the management of patients with concurrent hypertension and
      diabetes is therefore, urgently needed.

PMID- 21073074
TI  - G6PD enzyme activity in normal term Malaysian neonates and adults using a
      OSMMR2000-D kit with Hb normalization.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the commonest
      causes of neonatal jaundice in Malaysia. Screening of cord blood for G6PD
      deficiency by the semiquantitative fluorescent spot test (FST) is performed in
      Malaysia but this test can miss cases of partial G6PD deficiency. The OSMMR-D kit
      assay measures G6PD activity and hemoglobin (Hb) concentration, allowing direct
      expression of results in U/gHb. We evaluated this method and established the
      normal range for G6PD activity in normal term neonates and adults. EDTA blood
      from 94 neonates and 295 adults (age 15-59 years old) with normal Hb and FST were
      selected. The normal means for G6PD activity for neonates and adults were 12.43
      +/- 2.28 U/gHb and 9.21 +/- 2.6 U/gHb, respectively; the reference ranges for
      normal G6PD activity in neonates and adults were 10.15-14.71 U/gHb and 6.61-11.81
      U/gHb respectively. There were no significant differences in mean normal G6PD
      activity between the Malays and Chinese racial groups or between genders. The
      upper and lower limit cut-off points for partial deficiency in neonates were 7.4
      U/gHb (60% of the normal mean) and 2.5 U/gHb (20% of the normal mean),
      respectively. For adults, the upper and lower limit cut-off points for partial
      deficiency in adults were 5.52 U/gHb (60% of the normal mean) and 1.84 U/gHb (20%
      of the normal mean), respectively. The quantitation of G6PD enzymes using this
      OSMMR-D kit with Hb normalization was simple since the Hb was analyzed
      simultaneously and the results were reproducible with a CV of less than 5%.

PMID- 21073075
TI  - Iodine deficiency disorder among pregnant women in a tertiary care hospital of
      Kolkata, India.
AB  - The present unicentric, hospital based, non-interventional, cross-sectional study
      was undertaken to assess the iodine status of pregnant women attending the
      antenatal clinic at a medical college in Kolkata, India, during the different
      trimesters of pregnancy and to compare their iodine status with those of age
      matched non-pregnant control women. Assessment of the iodine status was based on
      urinary iodine excretion (UIE). Serum levels of free triiodithyronine (fT3), free
      thyroxine (fT4) and thyroid stimulating hormone (TSH) were assayed as an indirect
      measure of iodine status. A statistical comparison between the median values for
      UIE, TSH, fT4 and fT3 in pregnant women and non-pregnant controls revealed a
      significant difference between the median values for UIE (p < 0.0047), TSH (p <
      0.00001) and fT4 (p < 0.001). UIE and fT4 were significantly lower and TSH was
      significantly higher in pregnant women than in non-pregnant controls. However, no
      significant difference in median values for fT3 concentration between the groups
      was seen (p = 0.4). Only 4 cases out of 200 pregnant women had an UIE of less
      than the lower cut-off value for UIE recommended by the WHO corresponding to
      optimal iodine intake. The results indicate most pregnant subjects attending the
      antenatal clinic at Medical College Kolkata, India, a tertiary care institution,
      did not suffer from significant iodine depletion. This may be ascribed to
      increased awareness of this condition and the accessibility of iodized salt among
      the study population.

PMID- 21073076
TI  - Prevalence and factors affecting the use of tobacco, alcohol and addictive
      substance among university students in eastern Turkey.
AB  - This study investigated the prevalence and factors affecting the use of
      cigarettes, alcohol and addictive substances among university students in Eastern
      Turkey. This cross-sectional study was conducted on 2258 students at Firat
      University in the city of Elazig, eastern Turkey. The subjects were students,
      randomly selected from each department of the university. A questionnaire was
      administered to the students under direct observation. The mean age of the
      participants was 21.36 +/- 2.93 years. Twenty-nine point three percent of the
      students smoked and 26.9% used alcohol. Six point six percent declared they had
      used an addictive substance other than cigarettes or alcohol at least once during
      their lifetime. Students who smoked had a higher monthly family income and
      allowance than nonsmokers (p < 0.05). Smoking was more prevalent among students
      whose fathers, siblings or close friends also smoked (p < 0.05). The use of
      alcohol was higher among students whose close friends used alcohol (p < 0.05).
      Six point three percent of participants stated they knew classmates who used
      addictive substances other than cigarettes or alcohol, and 12.4% declared they
      knew friends outside the classroom who used addictive drugs. At Firat University
      a large proportion of students reported using alcohol or smoking. Access to
      addictive drugs was also prevalent. Educational programs oriented towards young
      people must be prioritized in order to raise awareness regarding substance use.

PMID- 21073077
TI  - Factors influencing the declining trend of vasectomy in Sichuan, China.
AB  - Vasectomy was once the most common birth control method in both Sichuan Province,
      China and the world. However, since the 1990s the prevalence of vasectomy in
      Sichuan, has declined significantly compared to female sterilization in Sichuan
      and national prevalence of male/female sterilization during the same period. To
      explore possible reasons for this decline, 27 focus group discussions (FGDs) and
      8 in-depth interviews (IDIs) were conducted in four strata of Sichuan. Procedures
      for qualitative data analysis were used. The findings reveal the decline in
      vasectomy in Sichuan Province is influenced by multiple factors, including shifts
      in demographics, changes in family planning working approach and people's
      perceptions of reproduction, lack of information and misunderstandings about
      vasectomy, the stereotype of male dominance, bias and preference of program and
      provider, and the impact of a market economy. Several implications arise from the
      study for future program development.

PMID- 21073078
TI  - Potentially hazardous environmental factors for poisoning in rural Vietnam: a
      community-based survey.
AB  - Poisoning represents one of the most common threats against public health. This
      population-based study was undertaken to identify potentially hazardous
      environmental factors for poisoning in Vietnam, and thereby to improve the
      background information needed to take adequate preventive measures. The study
      population comprised 3814 individuals from 942 randomly selected households in
      Phu Tho Province. Their mean age was 32.7 years, 50.4% were male. Data collection
      methods included face-to-face interviews using a structured questionnaire, and
      reality observations following a structured checklist. Of the study population,
      438 individuals (11.5%) recalled having suffered from at least one episode of
      symptomatic poisoning. The toxic agents most commonly involved in these incidents
      were pesticides (68.7%). Hazardous exposure to toxins was reported to occur
      frequently and pesticides were again the agents most commonly involved. The
      presence of insecticides and other pesticides in the home were common (39%) and
      21.7% of studied households kept poisonous chemicals in places easily accessible
      to children. Nearly half the households kept medications at home, often without
      any medical safe-box. Fifty-six point two percent reported prescriptions were not
      necessary for purchasing pharmaceuticals. Common habits among household members
      put them at risk for poisoning by natural toxins. Among these, frequent use of
      unusual herbs, and the practice of raising and eating poisonous animals were most
      important. In conclusion, the widespread use of pesticides, risk for exposure to
      natural toxins and self medication constitute major hazards for poisoning in
      Vietnam. Effective control regulations and safe strategies are lacking.

PMID- 21073079
TI  - Factors affecting adherence of antiretroviral treatment among AIDS patients in an
      Ethiopian tertiary university teaching hospital.
AB  - BACKGROUND: Higher level of antiretroviral adherence is associated with improved
      virological, immunological and clinical outcomes. Despite the availability of few
      studies in sub Saharan Africa the factors for poor adherence are diverse.
      OBJECTIVE: To determine adherence factors for antiretroviral treatment in Hawassa
      University teaching hospital in southern Ethiopia. PATIENTS AND METHODS: A cross
      sectional study was undertaken on total of 510 AIDS patients seen over one month
      period Data were collected using a structured questionnaire and analysis was done
      using SPSS 15.0. RESULTS: Out of interviewed patients 88.2% of them had > or =
      95% and 97.1% of them had > or =80% antiretroviral adherence rate by self report
      over one month period. The major reasons for missing drugs in 79.8% were
      forgetting to take drug, gastrointestinal symptoms, give priority for praying,
      being hopeless and inadequate adherence counseling Significant predictors of poor
      adherence were lower level of knowledge about adherence, absence of job and
      'Sidamnigna' as primary language. It is also observed that trend of adherence
      decreased as level of education decrease. CONCLUSIONS: Adherence rate found in
      this study is higher than many developed and developing countries and equivalent
      to other studies done in Ethiopia. Those who speak local language, jobless and
      having low education level may require intensive counseling to optimize their
      adherence.

PMID- 21073080
TI  - Quality of tuberculosis care in six health facilities of Afar Region, Ethiopia.
AB  - BACKGROUND: Quality tuberculosis care plays an important role in the status of
      tuberculosis (TB) control, treatment completion and adherence. Nonetheless, very
      little is known about the quality of TB care in public health facilities in
      Ethiopia. In this study we assessed the quality of TB care delivery in Afar
      Region of Ethiopia. METHODS: A descriptive cross sectional health institution
      based survey with both semi-structured and structured questionnaires was
      employed. A mix of complementary techniques was administered Data were collected
      between 5th February and 10th March 2007 from six health institutions. Records
      were reviewed for 270 patients, exit interviews were made for 209 patients, six
      providers were interviewed & 49 patients were observed Data was collected by
      trained nurses and analyzed using SPSS 11.0 statistical software. RESULTS: The
      study had showed that delivery of materials, drugs and supplies for tuberculosis
      control activities were fairly good. Staffing qualities were poor and patterns of
      supervision were weak. A relatively higher proportion of patients were
      dissatisfied with the appropriateness and adequacy of working hours (63.6%) and
      waiting time (70.3%). Statistically significant correlation was observed between
      process quality and output quality (clients' satisfaction) parameters (p <
      0.001). CONCLUSION: Continues quality improvement mechanisms to improve the
      different aspects of the programme and adherence to the National Tuberculosis and
      Leprosy Control Program guideline could be important interventions to enhance the
      quality of care delivery. An expanded community-based study to better guide
      quality DOTS program in pastoralist communities is crucial.

PMID- 21073081
TI  - Identification of drug susceptibility pattern and mycobacterial species in sputum
      smear positive pulmonary tuberculosis patients with and without HIV co-infection
      in north west Ethiopia.
AB  - BACKGROUND: Ethiopia is among the high-burden countries of tuberculosis (TB) in
      the world Since mycobacterial culture and susceptibility testing are not
      routinely performed in Ethiopia, recent data on susceptibility patterns and the
      mycobacterial species cultured from sputum smear positive patients are limited.
      OBJECTIVES: The aim was to determine first line anti-TB drug susceptibility of
      Mycobacterium tuberculosis isolates obtained from consecutive newly diagnosed
      smear positive pulmonary TB patients in north west Ethiopia. METHODOLOGY: A
      retrospective cross sectional study was conducted using previously collected
      sputum samples (n=180) kept at the referral hospital of the University of Gondar
      at -20 degrees C. Sputum samples were cultured on Lowenstein Jensen (LJ) medium.
      Conventional Polymerase Chain Reaction (PCR) using RD4 primers to identify the M.
      tuberculosis complex was performed on cultured isolates. Ninety eight (84.4%) of
      the 116 isolates identified as M. tuberculosis were tested for their drug
      susceptibility pattern using the proportion method Clinical baseline data
      including body mass index, body temperature, clinical symptoms and erythrocyte
      sedimentation rate were obtained. RESULTS: The culture retrieval rate of
      previously frozen sputum samples was 64.4% (116/180). All the isolated
      mycobacterial species (n=116) were confirmed as belonging to the M. tuberculosis
      complex by PCR. Of 98 isolates for which the drug susceptibility test was done,
      15.3% (15/98) were found to be resistant to one or more antimycobacterial drugs,
      and resistance to isoniazid and streptomycin was most common with 8.2% (8/98) and
      6.1% (6/98) respectively. TB patients co infected with HIV had increased
      erythrocyte sedimentation rate, higher age and lower sputum smear grade than HIV
      negative TB patients. CONCLUSIONS: No mycobacteria other than M. tuberculosis
      were detected in sputum smear positive TB-patients. Although no multi drug
      resistant strain was observed, relatively high rates of INH resistance were found
      in this region. Culture facilities are urgently needed in regional centers to
      increase diagnostic sensitivity and monitor developing trends of drug resistance
      in Ethiopia.

PMID- 21073082
TI  - Antibiotic use in obstetric fistula repair: single blinded randomized clinical
      trial.
AB  - INTRODUCTION: The beneficial effect of extended use over single dose of
      antibiotics in obstetric fistula repair is unknown, however, is practiced widely.
      METHODS: From September 2006 to February 2008, a total of 722 eligible women with
      obstetric fistula were randomly assigned to receive either of 80 mg Gentamycin IV
      (immediately after spinal anesthesia), or extended use of Amoxicillin,
      Chloramphenicol or Cotrimexazole (postoperatively) and followed post operatively.
      Post surgery progresses, interventions andfinal results were recorded on the
      standard format prepared. RESULTS: A total of 722 study participants were
      followed, the mean age was 25.1 years (24.6, 25.6), 90.4% were illiterate, 33.2%
      were divorced and 53.2% were injured during their first delivery. About 81% of
      women had bladder injury without rectal and anal sphincter involvement, and over
      70% had prolonged labor (labour lasted over 24 hours). Proportion of women with
      the above mentioned parameters was similar among the two groups. Additional
      procedures (Martius fat graft and minilaparatomy); the amount of blood loss; and
      the length ureteric catheters and vaginal pack stayed were not different among
      the two groups. The proportion of women with successfild fistula closure was
      similar among the two groups; 94.5% (92.1, 96.9) for single dose of Gentamycin
      vs. 89.4% (86.2, 92.6) for extended dose of other antibiotics. Hospital stay;
      proportion of women with fever, post repair infection; post operation stress
      incontinence and other residual incontinences were not different among the two
      groups. CONCLUSIONS: Single dose of Gentamycin (80 mg IV) given preoperatively at
      the administration of spinal anesthesia appears to be equally effective as the
      extended use of either of or combination of Amoxicillin, Chloramphenicol and
      Cotrimexazole.

PMID- 21073083
TI  - Assesment of household burden of orphaning and coping strategies by guardians and
      families with orphans and vulnerable children in Hossana Town, SNNPR.
AB  - BACKGROUND: Globally the number of orphans is increasing due to HIV/AIDS,
      internal corflicts and others. Orphanage and vulnerability causes much of its
      burden on poor households and children. OBJECTIVE: This study was initiated to
      assess household challenges of orphaning and coping strategies by families and
      guardians living with Orphan and Vulnerable Children (OVC). It has also tried to
      look at the types and level of challenge facing OVC. METHODOLOGY: Community based
      descriptive cross-sectional quantitative survey was conducted from October to
      November 2008 using a pre-tested Amharic questionnaire among guardians of OVC in
      Hossana town. Hadiya zone, SNNPR. A total of 334 samples were selected using a
      simple random sampling technique. RESULT: Sixty nine percent (69%) of guardians
      were women. Almost all of the OVC had participated in one domestic activity and
      26.9% of OVC were involved in domestic work in other houses. A little more than
      twenty two percent (22.2%) have history of involvement in productive child labor;
      of whom 79.7% were found working at the time of data collection Above thirty five
      percent (35.6%) of respondents believe that the OVC are discriminated and 23.5%
      of the discriminators were step parents. As household coping mechanism 24.9%
      reported selling domestic animals, 15.6% selling household equipments and 12.9%
      sell plots of land which all occurs due to lack of resources in households.
      CONCLUSION AND RECOMMENDATION: The study concluded that caregivers lack
      sufficient resources to provide basic needs to OVC. Hence, community based
      training on micro finance assistance, discrimination and psychological support
      should be given to guardians and the community in general.

PMID- 21073084
TI  - Patterns of lumbar myelographic findings in patients with LBP a 5 years
      retrospective study at Yehuleshet Higher Clinic, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Low back pain (LBP) is usually defined as pain, muscle tension, or
      stiffness localized below the costal margin and above the inferior gluteal folds,
      with or without leg pain (sciatica). LBP is a common health problem and the
      imaging of which need carful clinical diagnostic triage. Most of us will
      experience at least one episode of LBP during our life. Despite its burden to the
      health facilities, more than 90% have no identifiable organic cause so their
      diagnosis is based on exclusion of other specific pathologies. OBJECTIVE: The
      study asses level of association of LBP and lumbar Myelographic findings in a
      higher clinic in Addis Ababa and provide baseline information of patterns of
      lumbar myelographic disease. PATIENTS AND METHODS: This is a retrospective record
      review of patients with LBP for whom lumbar myelography was done at Yehuleshet
      Higher Clinic. Data were collected from the clinics record, both hard and soft
      copy records were used a total of 1688 patients who had lumbar myelography study
      done for a complaint of LBP in the years from 2002-2008 are included in the
      study. RESULTS: Among the study subjects 895 (53%) were males and 793 (47%) were
      females. Mean age was 42.41 +/- 13.22. 1073 (63.6%) had abnormal myelographic
      findings and the rest 615 (36.4%) had normal lumbar myelography. The commonest
      abnormality is disc prolapse 36.7% with L4-L5 and L5-S1 being the commonest
      sites. CONCLUSION: Even if lumbar myelography showed abnormal findings in 63.6% a
      significant number of the studies (36.4%) were normal indicating lack of optimal
      clinical triage. Overall in countries like ours, where the recommended primary
      imaging modality, i.e., MRI is inaccessible and expensive, the value of
      myelography is unquestionable. RECOMMENDATION: But because of the invasive nature
      of the examination which also uses radiation, a diagnostic clinical triage should
      be taken first before subjecting patients to Myelographic procedures. Further
      studies to assess the positive predictive value of myelography with surgical
      confirmation are recommended.

PMID- 21073085
TI  - Cryptococcal meningitis in patients with acquired immunudeficiency syndrome in
      prehaart era at Gondar College of Medical Sciences Hospital north-west Ethiopia.
AB  - BACKGROUND: CIyptococcal meningitis is an important opportunistic funimgal
      infection that became very common after the era of HIV infection. OBJECTIVES: To
      determine the magnitude of Clyptococcal meningitis and study the clinical pattern
      among inpatients with HV infection at Gondar Hospital. METHODS: A descriptive
      study was done among ELISA confirmed admitted HIV patients. Clinically suspected
      cases of meningitis underwent lumbar puncture and cerebrospinal fluid analysis.
      The clinical profile and outcomes of the confirmed Cryptococcal meningitis cases
      were described. RESULTS: Among 375 HIV serology positive patients 31 were
      confirmed to have Cryptococcal meningitis. Their median age was 29 years (range
      16-64); and 22 were males. The major manifestation at presentation included
      headache and fever each in 90% malaise (65%), stiffness of the neck (48%),
      altered Mentation (32%) and nausea and vomiting (32%), photophobia (23%) and
      seizure (3.6%). Median duration of illness was 16 days; ranging from 1-40 days.
      Temperature was above 38.4 degreees C in 80%. Meningial signs were observed in
      32% altered Mentation was noted in 29% and focal neurologic deficit in 19%
      Cerebrospinal fluid examination revealed visually increased pressure (measured
      opening pressure >200 mmH2O in six patients) in 81% glucose < 50 mg/dl (50-70 mg/
      dl) in 55% Protein >40 mg/dl (15-40 mg/dl) in 35% leukocytes count < 20/mm3 (poor
      prognostic sign) in 58% Indian ink staining detected encapsulated yeasts in 71%
      C. neoformans was cultivated in 90% of sample. Highest case fatality rate of the
      disease was observed during the pre HAART era. CONCLUSION: Cryptococcal
      Meningitis is common among patients with immune-suppression. It could be the
      initial manifestation of HIV infection and should be suspected in any potential
      HIV infected patient with neurological symptoms especially headache and fever. As
      it has highest case fatality rate, early diagnosis and prompt therapy is strongly
      recommended Better treatment options like boosting their immunity with HAART
      should also be investigated

PMID- 21073086
TI  - Case series of 2,4-D poisoning in Tikur Anbessa Teaching Hospital.
AB  - 2,4-D (2, 4 dichlophenoxy acetic acid) poisoning is a rare phenomenon, but it is
      appearing more frequently as agrochemical usage of these agents is increasing in
      Ethiopia. Here the clinical features and outcomes of three cases due to 2, 4-D
      poisoning are described and discussion is made with literature review.

PMID- 21073087
TI  - Osteochondroma of the coccyx: a case report.
AB  - Osteochondroma is the most common benign bone tumor. Majority of solitary
      osteochondromas are asymptomatic however, may give functional impairment due to
      pain from pressure or mass effect. Osteochondromas occur most often about the
      knee and picked incidentally, coccygeal osteochondroma however; is a rare
      occurrence. On a plain radiography, it typically appears as a bony projection
      with a clear cortex and medulla related to the coccyx. Here we present the case
      of a 7-year-old child with coccygeal osteochondroma.

PMID- 21073088
TI  - The past few months have been a time of considerable activity for the Royal Naval
      Medical Service.

PMID- 21073089
TI  - Is damage control surgery appropriate in vascular trauma in the field?

PMID- 21073090
TI  - Fixation and deformity correction by plate osteosynthesis of a tibial shaft
      malunion after traditional African bone setting.
AB  - Given the global nature of modern travel and the possibility of deployment to the
      African continent, it is conceivable that medical officers in the course of their
      general duties may be exposed to patients managed with traditional bone setting
      techniques. Whilst these techniques may prove effective for many, complications
      may still arise and their management may be challenging.

PMID- 21073091
TI  - Asthma and exercise; a testing issue?

PMID- 21073092
TI  - Case study--leprosy.
AB  - We present the case of a 26 year old Indian base worker who attended the Role 2
      enhanced hospital in Iraq with a case of leprosy. The patient presented four
      times over a 12 month period with non-specific pain in the right hand and forearm
      combined with a large lesion of dry skin and reduced sensation in the forearm. A
      clinical diagnosis of leprosy was made, which was subsequently confirmed as
      paucibacillary leprosy by skin smears sent to the UK. It was not possible to
      treat the patient locally and a recommendation made to the patient's employer
      that the patient return to India to commence treatment.

PMID- 21073093
TI  - HMS ARK ROYAL and the 2003 helicopter crash in the Northern Arabian Gulf.

PMID- 21073094
TI  - Notes from a small Scottish training scheme.

PMID- 21073095
TI  - 'Performing miracles': the importance of Royal Naval Medical Officers in
      operations 'Overlord' and 'Neptune' during World War II.

PMID- 21073097
TI  - AJOT publication priorities.

PMID- 21073096
TI  - Dietary hypersensitivity in cats and dogs.
AB  - Adverse reactions to food or dietary hypersensitivity are frequently seen
      problems in companion animal medicine and may be difficult to differentiate from
      inflammatory bowel disease (IBD). Dietary hypersensitivity can be divided into
      two subgroups: immunological and nonimmunological problems. Non-immunological
      problems can be subdivided into food intolerance, food poisoning, and dietary
      indiscretion. The immunological group can be subdivided into true food allergy
      (IgE mediated) and anaphylaxis (non-IgE mediated). This article gives an outline
      of what dietary hypersensitivity is, and more specifically food allergy and how
      to deal with patients with possible dietary hypersensitivity.

PMID- 21073098
TI  - Comparing three postoperative treatment protocols for extensor tendon repair in
      zones V and VI of the hand.
AB  - OBJECTIVE: This pilot study compared the effectiveness of 3 postoperative
      rehabilitation protocols for patients with Zones V and VI extensor tendon
      lacerations. METHOD: Twenty-seven patients were recruited from 3 sites and
      randomly assigned to 1 of 3 established treatment protocols: immobilization,
      early passive motion (EPM), and early active motion (EAM). Outcome measures were
      collected at 3, 6, and 12 wk after treatment and included total active motion
      (TAM). RESULTS: At the end of Week 12, data on 24 injured digits of 18 patients
      were available for analysis. When data at Weeks 3, 6, and 12 were compared,
      patients in all groups showed steady improvement in TAM, but digits under the EAM
      treatment improved to a greater extent over time (F[2, 46] = 75.6, p < .001).
      CONCLUSION: Patients with Zones V and VI extensor tendon injuries treated with
      the EAM protocol recovered range of motion more rapidly.

PMID- 21073100
TI  - Use of mental practice to improve upper-limb recovery after stroke: a systematic
      review.
AB  - OBJECTIVE: We sought to determine whether mental practice is an effective
      intervention to improve upper-limb recovery after stroke. METHOD: We conducted a
      systematic review of the literature, searching electronic databases for the years
      1985 to February 2009. We selected studies according to specified criteria, rated
      each study for level of evidence, and summarized study elements. RESULTS: Studies
      differed with respect to design, patient characteristics, intervention protocols,
      and outcome measures. All studies used imagery of tasks involving movement of the
      impaired limb. The length of the interventions and number of practice hours
      varied. Results suggest that mental practice combined with physical practice
      improves upper-limb recovery. CONCLUSION: When added to physical practice, mental
      practice is an effective intervention. However, generalizations are difficult to
      make. Further research is warranted to determine who will benefit from training,
      the dosing needed, the most effective protocols, whether improvements are
      retained, and whether mental practice affects perceived occupational performance.

PMID- 21073099
TI  - Five-year retrospective study of inpatient occupational therapy outcomes for
      patients with multiple sclerosis.
AB  - OBJECTIVE: This study was a retrospective chart analysis spanning 5 yr that
      investigated associations between occupational therapy interventions and goal
      based positive outcomes in patients with multiple sclerosis (MS) and related
      disorders at discharge in an urban inpatient rehabilitation setting. METHOD:
      Using descriptive statistics, we examined demographic characteristics in the
      first analysis phase. In the second phase, we performed a series of correlational
      analyses to identify treatment variables associated with positive outcomes.
      RESULTS: Generally, patients improved in their FIM scores at discharge.
      Increasing occupational therapy intensity had a positive effect on functional
      performance in all categories except feeding, with significant correlations in
      upper-extremity dressing (r = .153, p < .05) and memory (r = .204, p < .01).
      CONCLUSION: Occupational therapy was associated with positive functional outcomes
      for patients with MS. Future treatment protocols should include cognitive skills
      training, community reintegration, and self-care, because these treatments were
      found to be significantly correlated with positive changes in FIM scores.

PMID- 21073101
TI  - Effectiveness of rehabilitation in enhancing community integration after acute
      traumatic brain injury: a systematic review.
AB  - OBJECTIVE: We assessed evidence for post-acute traumatic brain injury (TBI)
      rehabilitation interventions used to enhance community integration (CI) relevant
      to occupational therapy. METHOD: We conducted a systematic review of intervention
      studies on TBI rehabilitation from 1990 to 2007. RESULTS: We analyzed and
      summarized 10 studies that met the inclusion criteria. Of 10 studies, 7 found
      that post-acute TBI rehabilitation benefits CI; all effective studies involved
      occupational therapy or involved interventions occupational therapists can do.
      CONCLUSION: Many CI programs show positive results and should be studied more
      rigorously. Such promising programs should also be considered when decisions
      about post-acute TBI rehabilitation services for clients are being made. To
      further establish that post-acute TBI rehabilitation interventions improve CI,
      future studies should include intervention strategies based on injury severity, a
      control group, and longer term follow-up. The role of occupational therapy in
      these effective programs should be further explored.

PMID- 21073102
TI  - Combined bracing, electrical stimulation, and functional practice for chronic,
      upper-extremity spasticity.
AB  - OBJECTIVE: Conventional methods for managing upper-extremity (UE) spasticity are
      invasive, usually require readministration after a certain time period, and do
      not necessarily increase UE function. This study examined efficacy of combining
      two singularly efficacious modalities-UE bracing and electrical stimulation-with
      functional training to reduce UE spasticity and improve function. METHOD: Two
      chronic stroke patients exhibiting UE spasticity were administered the Modified
      Ashworth Scale (MAS), the upper-extremity section of the Fugl-Meyer Impairment
      Scale (FM), the Box and Block Test (B&B), and the Arm Motor Ability Test (AMAT).
      They were then individually fitted for a brace and subsequently participated in
      treatment sessions occurring 2 days/wk for 5 wk, consisting of (1) 30-min
      clinical sessions, during which the UE was braced in a functional position while
      cyclic electrical stimulation was applied to the antagonist extensors of the
      tricep and forearm, and (2) 15-min, clinically based training sessions, occurring
      directly after the clinical session. RESULTS: After intervention, participants
      exhibited 1-point reductions in MAS scores for the affected fingers, FM score
      increases, and increased ability to perform AMAT activities,. Three months later,
      both participants retained these changes. CONCLUSION: Data point to a
      noninvasive, promising method of managing spasticity and rendering functional
      changes.

PMID- 21073103
TI  - Use of the Occupational Therapy Task-Oriented Approach to optimize the motor
      performance of a client with cognitive limitations.
AB  - This case report describes the use of the Occupational Therapy Task-Oriented
      Approach with a client with occupational performance limitations after a cerebral
      vascular accident. The Occupational Therapy Task-Oriented Approach is often
      suggested as a preferred neurorehabilitation intervention to improve occupational
      performance by optimizing motor behavior. One common critique of this approach,
      however, is that it may seem inappropriate or have limited application for
      clients with cognitive deficits. This case report demonstrates how an
      occupational therapist working in an inpatient rehabilitation setting used the
      occupational therapy task-oriented evaluation framework and treatment principles
      described by Mathiowetz (2004) with a person with significant cognitive
      limitations. This approach was effective in assisting the client in meeting her
      long-term goals, maximizing her participation in meaningful occupations, and
      successfully transitioning to home with her daughter.

PMID- 21073104
TI  - Use of occupations and activities in a modified constraint-induced movement
      therapy program: a musician's triumphs over chronic hemiparesis from stroke.
AB  - OBJECTIVE: This case report addresses the use of therapeutic occupations and
      activities within a modified constraint-induced movement therapy (mCIMT) approach
      for a 52-yr-old female violinist 4 yr after ischemic stroke. METHOD: Analysis of
      occupational performance was completed before and after intervention using a
      modified version of the Fugl-Meyer Sensorimotor Evaluation, the Motor Functioning
      Assessment, the Arm Improvement and Movement Checklist, and information obtained
      from a client journal maintained throughout treatment. The mCIMT protocol
      included use of constraint of the affected arm, with emphasis placed on
      participation in meaningful occupations and activities. RESULTS: Improved
      function in the affected extremity was noted at the conclusion of mCIMT. After
      completion of therapy, the client reported a return to playing violin.
      DISCUSSION: The findings from this case report suggest that use of meaningful
      occupations and activities integrated into a mCIMT protocol may be effective in
      addressing skills deficits for clients with upper-extremity chronic hemiparesis.

PMID- 21073105
TI  - Effects of a kinesthetic cursive handwriting intervention for grade 4-6 students.
AB  - OBJECTIVE: We studied whether Grade 4-6 students who participated in a
      kinesthetic writing intervention improved in legibility, speed, and personal
      satisfaction with cursive handwriting. METHOD: Small groups of students with
      handwriting difficulties were seen weekly for 7 wk using a kinesthetic writing
      system. A repeated measures design was used to evaluate change in global
      legibility, individual letter formation, specific features of handwriting, and
      personal satisfaction. RESULTS: Analysis revealed (1) a significant increase in
      ratings of global legibility (p <.01; clinically significant improvements in 39%
      of students); (2) significant improvements in letter formation and legibility
      features of baseline, closure, and line quality (all p < .05); (3) increased
      handwriting speed (p < .05; not clinically significant); and (4) significant
      increase in measures with personal satisfaction of handwriting (p < .01).
      CONCLUSION. A kinesthetic handwriting intervention may be effective in improving
      the skills of students with handwriting challenges.

PMID- 21073106
TI  - Examining content validity and reliability of the Assessment of Children's Hand
      Skills (ACHS): a preliminary study.
AB  - OBJECTIVE: We developed the Assessment of Children's Hand Skills (ACHS) to
      evaluate hand skills using naturalistic observation and examined the assessment's
      interrater and test-retest reliability. METHOD: We developed the hand skill
      framework, performed expert review, and pilot tested the ACHS. The ACHS's
      reliability was examined by recruiting 54 children (30 typically developing
      children and 24 children with disabilities). RESULTS: The test-retest reliability
      for the ACHS was satisfactory at the individual item level (0.42 < or = kappa <
      or = 0.79) and the total scale level (Spearman's p = 0.78, p < .01). Moderate
      interrater agreement of the total scale scores was demonstrated (p = 0.63, p <
      .01), but individual items exhibited varied interrater agreement. CONCLUSION: The
      ACHS demonstrated adequate content validity and preliminary reliability evidence
      and could be used to quantify children's hand skill use. Construct validity
      should be established in a clinical setting.

PMID- 21073107
TI  - Cross-regional validation of the School Version of the Assessment of Motor and
      Process Skills.
AB  - OBJECTIVE: The objective was to determine whether the School Version of the
      Assessment of Motor and Process Skills (School AMPS) is valid when used to
      evaluate students in different world regions. METHOD: Participants were 984
      students, ages 3-13 yr, from North America, Australia and New Zealand, United
      Kingdom, and the Nordic countries, matched for age and diagnoses. We used FACETS
      many-faceted Rasch analyses to generate item difficulty calibrations by region
      and evaluate for significant differential item functioning (DIF) and differential
      test functioning (DTF). RESULTS: Four School AMPS items demonstrated DIF but
      resulted in no DTF. CONCLUSION: This study provided support for occupational
      therapists using the School AMPS to evaluate students' quality of schoolwork task
      performances across regions because the School AMPS measures are free of bias
      associated with world region.

PMID- 21073108
TI  - Identifying strategies early intervention occupational therapists use to teach
      caregivers.
AB  - This study investigated early intervention occupational therapists' use of
      strategies to teach caregivers. A sample of 40 videotapes made by early
      intervention occupational therapists was randomly selected from an archival
      videotape data set of provider home visits. The sample included 20 videotapes
      illustrating traditional services and 20 videotapes illustrating therapists
      providing participation-based services. Videotapes were rated using the Teaching
      Caregivers Scale, which rates three variables on 30-s intervals: (1) routine, (2)
      provider role, and (3) strategies used to teach caregivers during early
      intervention home visits. Regardless of the model of service, explicit teaching
      strategies were rarely used during home visits.

PMID- 21073109
TI  - Promoting healthy lifestyles with aging: development and validation of the Health
      Enhancement Lifestyle Profile (HELP) using the Rasch measurement model.
AB  - This study was conducted to develop and validate the Health Enhancement Lifestyle
      Profile (HELP), a self-report measure for examining various aspects of health
      related lifestyle in older adults. Data derived from 253 community-dwelling older
      adults were analyzed through the Rasch measurement model. Unidimensionality and
      data-model fit of HELP were largely supported through the analyses of principal
      components of residuals, fit statistics, local dependency, and differential item
      functioning. The item hierarchy formed through logits provided an expected
      pattern of healthy lifestyle behaviors. Acceptable to good person separation and
      reliability statistics supported the clinical applicability and consistency of
      the HELP scores. Finally, analysis of the rating scale structure confirmed the
      functioning of the 0- to 5-point rating scale used. HELP can assist in monitoring
      lifestyle risk factors and measuring the outcome of services aimed at promoting
      healthy lifestyles among older adults.

PMID- 21073110
TI  - Development and evaluation of the University of Michigan's Practice-Oriented
      Research Training (PORT) Program.
AB  - We describe the development and evaluation of a clinical research training
      program designed specifically for such health professionals as occupational and
      physical therapists. Outcomes of program success included trainees' self-rating
      of research skills before and after the program, as well as submission of a
      formal grant application to a grant competition for program participants. At
      program completion, participants reported improvements in their research skills,
      with the most gain in formulating research questions and writing a testable
      hypothesis and the least gain in understanding statistics. Of the 21
      participants, 43% submitted a grant proposal to a competitive intramural grant
      program. In the next year, grantees of the program will continue to be mentored
      by the program mentors while conducting their research projects. Given the
      initial successes, this program represents a promising model for providing
      research training to practicing clinicians.

PMID- 21073111
TI  - Transporting children in wheelchairs in passenger vehicles: a comparison of best
      practice to observed and reported practice in a pilot sample.
AB  - OBJECTIVE: We compared observed and reported practice among children with special
      health care needs transported in wheelchairs with the recommendations from the
      American National Standards Institute/Rehabilitation Engineering and Assistive
      Technology Society of North America Committee on Wheelchairs and Transportation
      voluntary standards for best practice for using wheelchairs in vehicles. METHOD:
      A convenience sample of vehicles exiting the garage of a children's hospital was
      observed. Certified child passenger safety technicians gathered driver
      demographics and the child's reported medical condition, weight, age, clinic
      visited, and relation to the driver. Technicians observed how the wheelchair and
      occupant were secured. RESULTS: A sample of 20 vehicles showed that 90% used four
      point tie-down systems to secure the wheelchairs. A total of 88% of drivers tied
      the wheelchairs down correctly; only 20% used a separate lap-shoulder belts to
      secure the occupants. Twenty-five percent used lap trays, which are not
      recommended. Fifteen participants traveled with medical equipment secured
      inappropriately. CONCLUSION: Many deviations from best practice were observed and
      highlight areas for increased awareness, education, and resources for caregivers.

PMID- 21073112
TI  - New assessment of forearm strength: reliability and validity.
AB  - OBJECTIVE: The objective was to determine the reliability of a portable forearm
      strength hydraulic dynamometer with a doorknob handle and assess its validity
      compared with a Cybex 6000 (Cybex International, Inc., Medway, MA) isometric
      torque assessment. METHOD: Eighteen volunteers (with a total of 30 forearms)
      participated in this one-session methodological study to determine the intra- and
      interrater reliability and criterion validity of a forearm dynamometer. RESULTS:
      Intrarater reliability for both assessors for pronation was (intraclass
      correlation coefficient [ICC](3,1) = .937-.961) and for supination was (ICC(3,1)
      = .923-.968). Interrater reliability for pronation was ICC(3,2) = .927 and for
      supination was ICC(3,2) = .847. Criterion validity of the Baseline hydraulic
      dynamometer (Fabrication Enterprises Inc., White Plains, NY) compared with the
      Cybex 6000 was .574-.664 for pronation and .749-.750 for supination. CONCLUSION:
      The Baseline hydraulic dynamometer with a more functional doorknob handle had
      good intra- and interrater reliability and demonstrated moderate validity
      compared with Cybex 6000 strength testing.

PMID- 21073113
TI  - Child and youth practice area publications in the American Journal of
      Occupational Therapy in 2008 and 2009: a content analysis, methodology overview,
      and summary.
AB  - In this review, 39 articles published in the American journal of occupational
      therapy in 2008 and 2009 that were categorized in the practice area of children
      and youth were examined using content analysis. The most frequent type of
      research published was basic research, which accounted for 38.5% (n=15) of the 39
      studies published on the topic. Instrument development and testing and
      effectiveness studies were the next two most frequently noted research
      approaches, accounting for 25.6% (n=10) and 20.5% (n=8) of the studies,
      respectively. Among the 8 effectiveness studies, the level of evidence
      distribution was as follows: Level I, 3; Level III, 2; Level IV, 1; and Level V,
      2. Quantitative studies were the predominant research paradigm used with 76.9%
      (n=30) of the studies.

PMID- 21073114
TI  - Selection of elite athletes, hormones and genes.

PMID- 21073115
TI  - Association of serum adiponectin levels with artherosclerosis and the metabolic
      syndrome in obese children.
AB  - BACKGROUND: The atherosclerotic process starts at an early age and is linked to
      obesity. However, the exact pathophysiological mechanism is poorly understood.
      OBJECTIVE: To investigate the relationship between serum adiponectin and
      metabolic syndrome and early arteriosclerosis. SUBJECTS: 176 obese and 88 normal
      children. METHODS: Ultrasound measurement was performed to investigate IMT, FMD,
      carotid artery compliance (CAC). Adiponectin was measured by enzyme-linked
      immunosorbent assay. RESULTS: Adiponectin levels correlated negatively with obese
      markers, blood pressure, fasting insulin, high sensitive CRP, HOMA-IR and IMT;
      marginally positively associated with CAC and HDL-c. The risk of metabolic
      syndrome increased 3.43 times when adiponectin levels were less than 7060 ng/ml.
      Heavy obesity, hypertension, low HDL-c, fasting hyperinsulin, High LDL-c and
      metabolic syndrome percentage were different in three groups according to the cut
      off value of adiponectin. CONCLUSIONS: Low adiponectin levels are associated with
      a high incidence of metabolic syndrome.

PMID- 21073116
TI  - Septo-optic dysplasia.

PMID- 21073117
TI  - Hyperandrogenism among elite adolescent female athletes.

PMID- 21073118
TI  - Confirmation of neonatal screening: reference intervals and evaluation of
      methodological changes in TSH measurement.
AB  - Neonatal reference values for serum thyrotropin are scarce and comprise only
      small numbers of patients. During 2006, changes were made in IMMULITE kits for
      TSH measurement. To validate methodological changes, 80 serum samples from
      patients were evaluated and to establish reference intervals, 334 neonates and
      infants were analyzed (divided into 4 groups). Group 1 (G1) (48-72 h of life)
      (n=153), group 2A (G2A) (7-10 days of life) (n=65), group 2B (G2B) (11-14 days of
      life) (n=35), group 3 (G3) (28-40 days of life) (n=81). Current kits overestimate
      TSH results by 26 to 37%; TSH (mIU/L) reference intervals (percentile 2.5-97.5)
      were G1 (1.1-12.7), G2A (1.8-9.8), G2B (1.1-7.1) (p < 0.03 vs. G2A), G3 (1.2
      6.9). We suggest that during the second week of life, reference values should be
      divided into an early stage and a late stage, at least, for there to be an
      adequate interpretation of borderline measurements in newborn thyroid screening.

PMID- 21073119
TI  - Antihyperlipidemic agents cause a decrease in von Willebrand factor levels in
      pediatric patients with familial hyperlipidemia.
AB  - Familial hyperlipidemia is a group of genetic disorders with a predisposition to
      atherosclerosis. Hyperlipidemia causes increased atherosclerotic events through
      increased endothelial damage. In this report we aimed to measure the plasma
      fibrinogen and von Willebrand factor antigen (VWf:Ag) levels in pediatric
      patients with familial hyperlipidemias and to investigate the effects of serum
      lipid levels and antihyperlipidemic agents on these parameters. Of the 41
      patients analyzed, vWf:Ag level was significantly lower in antihyperlipidemic
      receivers (132 +/- 51%, 102 +/- 19%; p = 0.010). This finding may indicate that
      early initiation of antihyperlipidemics in patients with familial hyperlipidemias
      may decrease the risk of future atherosclerotic events through not only
      decreasing the serum lipid levels, but also decreasing plasma vWf:Ag levels.

PMID- 21073120
TI  - GHR and VDR genes do not contribute to the growth hormone (GH) response in GH
      deficient and Turner syndrome patients.
AB  - We have prospectively assessed the influence of GHR and VDR gene polymorphisms on
      the response to rhGH therapy in Venezuelan children with growth hormone
      deficiency (GHD, n=28) and Turner syndrome (TS, n=25). Clinical data during rhGH
      treatment were compared in GH and TS patients with different genotypes. PCR
      amplifications were performed to obtain the genotype frequencies of the
      polymorphisms. Clinical data at the start of treatment and rhGH doses were
      indistinguishable among patients with GHD or TS with different GHR or VDR
      genotypes. After the first two years of rhGH treatment, clinical data in both GHD
      and TS patients were not different according GHR or VDR genotypes. In addition,
      there was no significant difference among the subjects when both these genotypes
      were combined. Gene polymorphisms in low penetrance genes do not contribute to
      the rhGH therapy response in patients with GHD and TS.

PMID- 21073121
TI  - Is BaF3 bioassay useful to identify patients with bioinactive growth hormone?
AB  - We analyzed the ability of the BaF3 cell line bioassay to select patients with
      biologically inactive GH. We first evaluated the biological response of the Ba/F3
      hGHR cells to rhGH additional doses from 10 to 5000 pg/ml. The concentration
      points corresponding to the linear part of the curve were selected. We then
      analyzed a group of sera, diluted like the standard, including the entire range
      of GH concentrations that can be analyzed by bioassay. The serum/standard area
      below the curve ratio was calculated. Serum GH immunoactivity determined by
      IMMULITE/GH bioactivity ratios was calculated. Our experimental data showed that
      GH-bioactivity/GH-immunoactivity ratios below 0.303 are indicative of a
      bioinactive GH molecule. This bioassay would recognize only extreme cases of GH
      bioinactivity, and it would not be a useful tool in the search for patients with
      altered forms of GH.

PMID- 21073122
TI  - Genital surgery for disorders of sex development: implementing a shared decision
      making approach.
AB  - Ongoing controversy surrounds early genital surgery for children with disorders
      of sex development, making decisions about these procedures extraordinarily
      complex. Professional organizations have encouraged healthcare providers to adopt
      shared decision-making due to its broad potential to improve the decision-making
      process, perhaps most so when data are lacking, when there is no clear "best
      choice" treatment, when decisions involve more than one choice, where each choice
      has both advantages and disadvantages, and where the ranking of options depends
      heavily on the decision-maker's values. We present a 6-step model for shared
      decision-making in decisions about genital surgery for disorders of sex
      development: (1) Set the stage and develop an appropriate team; (2) Establish
      preferences for information and roles in decision-making; (3) Perceive and
      address emotions; (4) Define concerns and values; (5) Identify options and
      present evidence; and (6) Share responsibility for making a decision. As long as
      controversy persists regarding surgery for DSD, an SDM process can facilitate the
      increased sharing of relevant information essential for making important health
      care decisions.

PMID- 21073123
TI  - Mean platelet volume in obese adolescents with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the accumulation of
      excess fat in the liver in the absence of alcohol consumption, which commonly
      coexists with obesity. NAFLD is associated with increased risk of atherosclerosis
      and insulin resistance. Mean platelet volume (MPV) is a marker of platelet
      activation, which is a determinant of atherosclerosis. AIMS: The first aim of the
      present study was to investigate the MPV levels in obese adolescents and compare
      the MPV levels in patients with and without NAFLD and also with healthy controls.
      The second aim of this study was to evaluate the relationship between IR and MPV.
      PATIENTS AND METHODS: Case records of 128 exogenous obese adolescents were
      retrospectively evaluated. Laboratory parameters were collected by using a
      computerized patient database. Insulin resistance was calculated by a homeostasis
      model assessment (HOMA-IR) index. Patients were divided into two groups: patients
      with NAFLD (Group 1) and patients without NAFLD (Group 2). Forty-seven healthy
      children constituted the control group. RESULTS: MPV was significantly higher in
      obese adolescents than their healthy peers. Group 1 had significantly higher MPV
      than group 2. HOMA-IR was significantly higher in group 1 than group 2. MPV was
      significantly higher in patients with IR than patients without IR. There was a
      positive correlation between MPV and HOMA-IR. MPV was inversely correlated with
      HDL cholesterol and platelet count. CONCLUSION: MPV may be used as a follow-up
      marker in patients with NAFLD at the point of atherosclerosis.

PMID- 21073124
TI  - Congenital hypothyroidism: etiology.
AB  - The etiology of congenital hypothyroidism (CH) is important in determining its
      severity, prognosis, genetic counseling and clinical management. AIMS:
      investigate the causes of CH and their severity using serum levels of FreeT4 and
      TSH. PATIENTS AND METHODS: 243 neonates with CH (61% were girls) diagnosed by the
      Neonatal Screening Program of Minas Gerais between 1996 and 2003. The thyroid
      function was assessed through serum FreeT4 and TSH by chemilumiscence. CH
      etiology was evaluated by ultrasonography, scintigraphy, potassium perchlorate
      discharge test and serum thyroglobulin levels. RESULTS: Out of 243 patients,
      dysgenesis was found in 114 (47%): 3.3% had athyreosis; 0.4% eutopic dysgenetic
      gland due to maternal use of 131I; 22% ectopic glands (8.6% an isolated ectopic
      gland and 13% also an eutopic dysgenetic thyroid); 9% eutopic dysgenesis, 8.6%
      hypoplasia and 3.7% hemiagenesis. Thyroid in situ was found in 129 (52%): 23.5%
      had iodide organification defect; 3.7% thyroglobulin synthesis defect; 6.2% other
      0.4% dyshomonogenesis; iodide transport defect; 1.2% transient CH and 18% a
      normal gland. Patients with dysgenesis had a more severe CH than those with
      thyroid in situ (TSH 248.08 vs. 18.17 microIU/mL and FT4 0.32 vs. 0.95 ng/dL, p <
      0.001). CONCLUSIONS: Some cases had more complex dysgenesis, presenting ectopia
      associated to a dysgenetic eutopic gland. The ultrasound was the best tool to
      detect the dysgenetic tissue, but the scintigraphy was the most effective in
      identifying the functioning tissue. The thyroid hormone synthesis defects were
      found more frequently than expected, but in some cases they could not be defined.

PMID- 21073125
TI  - Familial hyperinsulinism-hyperammonemia syndrome in a family with seizures: case
      report.
AB  - Hyperinsulinism-hyperammonemia (HI/HA) syndrome is the second most frequent cause
      of congenital hyperinsulinism (CHI) and it is characterized by recurrent
      symptomatic hypoglycemia and persistent hyperammonemia. We describe the familial
      case of a 2-year-old child and her 32-year-old mother who, having suffered from
      tonic-clonic seizures since infancy, had both been diagnosed with epilepsy and
      treated with sodium valproate. Hypoglycemia was identified in the child in
      routine analysis. Six days after admission, a complete study of hypoglycemia
      showed test results compatible with hyperinsulinemic hypoglycemia and
      hyperammonemia. A mutation in the GDH gene (Arg269His) confirmed the diagnosis in
      both the mother and the child. An important peculiarity of this case is the
      diagnosis of a 32-year-old woman, previously diagnosed with epilepsy through her
      daughter's diagnosis at a Pediatric Endocrinology Department and subsequently
      treated ineffectively with sodium valproate. We conclude that, as hypoglycemia
      may be subtle, the diagnosis of HI/HA should be considered in children or adults
      with seizures/epilepsy and hyperammonemia, serum ammonia being a simple screening
      test for the disease.

PMID- 21073126
TI  - Genital sanguineous discharge in prepuberty: a case of mullerian papilloma of
      vagina in a nine-year-old girl.
AB  - Vaginal bleeding in prepuberty is an alarming symptom that must be carefully
      investigated. Among quite common causes of genital sanguineous discharge, there
      are rarer conditions responsible for bleeding at this age like Mullerian
      papilloma of the genital tract. In this report, we describe a case of Mullerian
      papilloma of the vagina in a 9-year-old girl. We believe in the importance of a
      correct clinical setting and histological definition to avoid wrong diagnosis and
      consequent inadequate treatments. Mullerian papilloma, a benign tumor, can in
      fact be treated only with local excision.

PMID- 21073127
TI  - Glycogen storage disease type III with hypoketosis.
AB  - A rare case of glycogen storage disease type III with unusually absent ketone
      body production during hypoglycemia is presented. A 10-month-old boy presented
      with asymptomatic hepatomegaly. GOT/GPT 2555/1160 IU/L, CK 302 IU/L,
      triglycerides 1223 mg/dL, cholesterol 702 mg/dL and uric acid 7.9 mg/dL. After a
      9-hour fast, glucose was 27 mg/dL and adequate lipolysis without ketogenesis was
      observed (total/free carnitine 34.5/20 micromol/L, free fatty acids 1620
      micromol/L and beta-hydroxybutyrate 172 micromol/L). Result of MCT (medium-chain
      triglycerides) load test: basal hydroxybutyrate 29 micromol/L rose to 5748
      micromol/L. Treatment with a fat-restricted diet supplemented with formula
      containing MCT was initiated and the patient presented a satisfactory initial
      evolution. Three months later, CK were 3000 IU/L. Muscle biopsy was diagnostic of
      glycogenosis. Enzymatic activity in skin fibroblasts was 0% for amylo-1,6
      glucosidase. The diagnosis of glycogenosis type III was established.
      Echocardiography performed at that time showed non-obstructive ventricular
      hypertrophy. Until now hypoketosis during hypoglycemia has only been described in
      glycogenosis type I.

PMID- 21073128
TI  - McCune-Albright syndrome (MAS): early and extensive bone fibrous dysplasia
      involvement and "mistaken identity" oophorectomy.
AB  - BACKGROUND: McCune-Albright syndrome (MAS) is a triad of gonadotropin-independent
      precocious puberty (GIPP), cafe-au-lait spots (CALS) and fibrous dysplasia (FD)
      of bone. The extent of the abnormalities is variable. PATIENT AND RESULTS: We
      report a 3 year old girl with CALS since infancy, FD diagnosed at age of 2.5
      years, and at the age of 3 years vaginal bleeding. The ultrasound revealed a
      cystic mass of the ovary, surgical pathology found ovarian cyst. LHRH stimulation
      demonstrated GIPP (LH 9.8 mIU/ml and FSH 8.9 mIU/ml; normal LH 1.8-10, FSH 9-26
      mIU/ml). Radiographs and bone scans demonstrated FD in multiple bones. Peripheral
      leucocytes and the ovary were negative for GNAS gene mutations. Treatment with
      Letrasole interrupted the pubertal development. CONCLUSIONS: We conclude that the
      clinical signs of MAS are telling and that timely MAS diagnosis prevents
      unnecessary oophorectomy. A close follow up is recommended regarding development
      of endocrine disorders and spreading of FD.

PMID- 21073129
TI  - Two new unrelated cases of hereditary 1,25-dihydroxyvitamin D-resistant rickets
      with alopecia resulting from the same novel nonsense mutation in the vitamin D
      receptor gene.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) an important regulator of bone
      homeostasis, mediates its actions by binding to the vitamin D receptor (VDR), a
      nuclear transcription factor. Mutations in the VDR cause the rare genetic disease
      hereditary vitamin D resistant rickets (HVDRR). In this study, we examined two
      unrelated young female patients who exhibited severe early onset rickets,
      hypocalcemia, and hypophosphatemia. Both patients had partial alopecia but with
      different unusual patterns of scant hair. Sequencing of the VDR gene showed that
      both patients harbored the same unique nonsense mutation that resulted in a
      premature stop codon (R50X). Skin fibroblasts from patient #1 were devoid of VDR
      protein and 1,25(OH)2D3 treatment of these cells failed to induce CYP24A1 gene
      expression, a marker of 1,25(OH)2D3 action. In conclusion, we identified a novel
      nonsense mutation in the VDR gene in two patients with HVDRR and alopecia. The
      mutation truncates the VDR protein and causes 1,25(OH)2D3 resistance.

PMID- 21073130
TI  - Secondary hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing
      loss in the subacute and chronic phases.
AB  - This study investigated the efficacy of hyperbaric oxygen therapy (HBOT) as a
      secondary treatment for patients with idiopathic sudden sensorineural hearing
      loss (ISSNHL) in the subacute and chronic phases. Forty-eight ISSNHL patients
      (HBOT group) who had received primary conventional treatment within 4 weeks after
      onset and underwent HBOT between 4 and 20 weeks post-onset were retrospectively
      compared with 44 ISSNHL patients (control group) with primary conventional
      treatment alone. Mean hearing gain was slight, with gains of 5.2 +/- 8.9 dB in
      the HBOT group and 2.0 +/- 7.6 dB in the control group. However, no significant
      difference was recognized between the two groups. In the HBOT group, no
      significant difference was observed in hearing gain among patients with HBOT
      initial time at 4-7, 8-11, 12-15 or 16-20 weeks after onset. Meanwhile, hearing
      gain was significantly higher in patients with profound hearing loss than in the
      other patients. We conclude that the effectiveness of secondary HBOT for ISSNHL
      patients in either subacute or chronic phase remains unproven, and thus, the
      decision administer HBOT should be made with caution.

PMID- 21073131
TI  - Cerebral blood flow and metabolism during mild hypothermia in patients with
      severe traumatic brain injury.
AB  - Cerebral blood flow (CBF) measurements during mild hypothermia therapy were made
      in 30 adult patients with severe head injuries (Glasgow Coma Scale score < or
      =18), by xenon enhanced computed tomography (Xe-CT). All patients but one
      underwent removal of hematomas and decompressive craniectomy. Immediately after
      surgery, hypothermia was induced by surface cooling, and a brain temperature of
      32-35 degrees C was maintained for 3 days. During hypothermia therapy, CBF
      measurements by Xe-CT were made for all patients on post-injury days 1 to 4. From
      the arteriovenous-oxygen content difference and CBF values, the cerebral
      metabolic rate of oxygen (CMRO2) values were obtained. Outcome was assessed at
      discharge according to the patients' Glasgow Outcome Scale (GOS) scores. Patients
      were divided into two groups based on their outcomes. Nineteen patients (63%)
      showed good outcomes (GOS score of 4 or 5) and 11 (37%) showed poor outcomes (GOS
      score of 1, 2, or 3). Statistically significant differences were obtained for the
      mean global CBF and CMRO2 values between the good and poor outcome groups. In
      this study, we demonstrated that CBF measurement may be useful to predict
      neurological outcomes following severe traumatic brain injury in patients
      undergoing hypothermia as well as to identify those who might not likely benefit
      from hypothermia therapy.

PMID- 21073132
TI  - Irradiation-induced p53 expression is attenuated in cells with NQO1 C465T
      polymorphism.
AB  - NAD(P)H:quinone acceptor oxidoreductase (NQO) 1 polymorphism is associated with
      various hematological malignancies, especially infant leukemia or therapy-related
      leukemias, which involve the rearrangement of mixed lineage leukemia (MLL) gene.
      Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (EBV-LCLs) with
      either of 2 well known polymorphic variations of C609T and C465T were selected
      from our archives of EBV-LCL clones and studied the induction of p53 expression
      after DNA damage. Irradiation of cells with C609T/C609T polymorphism (NQO1 *2*2)
      did not affect the induction of p53 expression. However, irradiation of cells
      with C465T/WT polymorphism (NQO1 *1*3) resulted in attenuation of p53 and p21
      induction. Our results suggest that increased risk of infant leukemia development
      in patients with NQO1 *1*3 polymorphism is partially dependent on the inhibition
      of p53 pathway, though further studies are needed to fully understand the
      pathological role of C465T variant in the development of childhood leukemia.

PMID- 21073133
TI  - Association between positional changes in laboratory values and severity in
      subjects with obstructive sleep apnea syndrome.
AB  - INTRODUCTION: The aim of the study was to investigate the association between the
      difference (defined as the remainder, Rm) in laboratory values determined in the
      upright and supine positions and the severity of obstructive sleep apnea syndrome
      (OSAS). MATERIALS AND METHODS: Thirty-three Japanese male subjects with OSAS
      [apnea/hypopnea index (AHI: the number of apneas and hypopneas per hour) > or =5]
      underwent cephalometric analysis and measurements of nasal resistance in the
      upright and supine positions. Several parameters in a dental model and physical
      features were also analyzed. RESULTS: Significant associations of the logarithmic
      AHI, with neck depth, Rm for the facial axis, and the minimum airway behind the
      tongue in the supine position were found in multiple linear regression analysis.
      CONCLUSION: Our results suggest that neck depth, Rm for the facial axis and the
      minimum airway behind the tongue in the supine position may be determinants of
      the severity of OSAS.

PMID- 21073134
TI  - HER-2/neu cytoplasmic staining is correlated with neuroendocrine differentiation
      in breast carcinoma.
AB  - HER2 oncoprotein plays an essential role in breast cancer growth and
      differentiation. Determination of HER2 status contributes not only to predicting
      survival but also to selecting the patients for anti-HER2 therapy. HER2 protein
      expressed in human cancer cells often contains variant forms as well as the full
      length wild-type form. In the present study, we investigated the subcellular
      localization of HER2 protein in 1053 primary breast cancer tissues. HER2 protein
      was stained by various immunohistochemical methods and studied by immunoelectron
      microscopy to confirm the intracellular localization. Thirty-four of 1053
      specimens showed cytoplasmic staining of the intracellular domain of HER2 protein
      by the HercepTest and CB-11. In contrast, no immunoreactivity to the antibodies
      against the extracellular domain was observed. None of the 34 specimens showed
      amplification of the HER2 protein by fluorescence in situ hybridization.
      Subsequently, we studied the association of the cytoplasmic expression of HER2
      with neuroendocrine differentiation. Interestingly, all 34 specimens had some
      positive signals of neuroendocrine markers such as synaptophysin, chromogranin A,
      neuron-specific enolase, and CD56. Although the result is preliminary, it
      warrants further study on the role of the cytoplasmic variant form of HER2 in
      breast cancer growth, particularly in the aspect of neuroendocrine
      differentiation.

PMID- 21073135
TI  - Predictive value of CD24 and CD44 for neoadjuvant chemotherapy response and
      prognosis in primary breast cancer patients.
AB  - PURPOSE: We investigated the significance of CD24 and CD44 expression for
      predicting responses to chemotherapy and prognosis in primary breast cancer
      patients. PATIENTS AND METHODS: Diagnosis of breast cancer was confirmed by core
      needle biopsy, and immunohistochemical studies were performed. Preoperatively,
      patients received anthracycline-containing chemotherapy. Expression of CD44 and
      CD24 was assessed immunohistochemically and the relationship with chemotherapy
      response and with prognosis was analyzed. RESULTS: Between 2001 and 2004, 139
      women were enrolled in this study. In the correlation analysis, CD24 expression
      was negatively associated with pathological response to chemotherapy (p =
      0.0003). A machine learning technique with an alternating decision tree (ADTree)
      showed that four logical rules are involved in predicting the response depending
      on the combination of CD24, HER2, tumor stage, CD44, progesterone receptor, and
      patient age. In the survival analysis, patients having CD44 (++) showed a
      significantly favorable prognosis as compared with others (p = 0.0002). A
      multivariate analysis showed that CD44 expression had an independent prognostic
      value (p < .0001). CONCLUSION: We found a significant correlation between CD44
      expression and prognosis and between CD24 expression and response to
      chemotherapy. CD24 and CD44 expressions would be useful predictive markers,
      although further studies are needed.

PMID- 21073136
TI  - A delayed recall battery as a sensitive screening for mild cognitive impairment:
      follow-up study of memory clinic patients after 10 years.
AB  - OBJECTIVE: I examined the predictive value of the combination of three delayed
      recall tests to distinguish (1) those with probable Alzheimer's disease (AD) from
      those within normal range, and (2) those with Mild cognitive impairment (MCI)
      from those within normal range. The data from 90 visitors to a memory clinic in
      Tokyo was used. I first examined patients clinically, neuroradiologically, and
      excluded the mental and neurological illness. AD was diagnosed according to the
      NINCDS-ADRDA criteria, MCI according to the criteria of Petersen et al.. Normal
      must be free from any disease examined above. METHODS: After the diagnosis, the
      baseline neuropsychological tests were performed for all participants; the Mini
      Mental State Examination, Raven's Colored Progressive Matrices, the Stroop Test,
      a 10-words list learning and recall test, a story recall test, and the Rey
      Osterrieth Complex Figure Test. After 10 years, all patients were reassessed and
      diagnosed again. RESULTS: Of the MCI patients for follow-up (n=29), 19 were
      converted to AD, while 5 not. One died. 4 lost. All AD patients (n=30) remained
      as AD. The combination of 3 delayed recall battery provides clinically useful
      predictive values for both AD and MCI in a memory clinics and dementia research
      clinics.

PMID- 21073137
TI  - Parasitic zoonoses in present day Europe.

PMID- 21073138
TI  - Factors of occurrence of ocular toxoplasmosis. A review.
AB  - Acquired and congenital toxoplasmosis are frequently complicated by ocular
      toxoplasmosis. The diagnosis relies on clinical aspects, response to specific
      treatment and results of biological assays. The incidence and the prevalence of
      this complication are difficult to establish precisely and depend on the
      prevalence of the parasite infection in the general population, and are affected
      by factors such as type of exposure to the parasite, genetic backgrounds of the
      parasite and the host, and type of immune response elicited by the parasite.

PMID- 21073139
TI  - Risk factors for Toxoplasma infection in pregnant women in FYR of Macedonia.
AB  - The aim of the study was to identify risk factors for Toxoplasma gondii infection
      in pregnant women in FYR of Macedonia. Retrospective analysis of serological and
      epidemiological data in a series of 235 pregnant women from Macedonia, tested for
      Toxoplasma infection between January 2004 and December 2005, showed an overall
      prevalence of infection of 20.4%. Exposure to transmission factors significantly
      increased the risk of infection (RR = 1.989, 95 % CI = 1.041-3.800, p = 0.037).
      The single infection transmission factor that was a predictor of infection in the
      whole series was exposure to soil (RR = 1.946, 95% CI = 1.026-3.692, p = 0.041).
      Based on prevalence and the established risk factors for Toxoplasma infection in
      Macedonia, the health education programme as a sustainable measure for the
      prevention of congenital toxoplasmosis should focus on educating women of
      generative age to avoid contact with soil (farming, gardening), and/to adhere to
      strict hygienic practices afterwards.

PMID- 21073140
TI  - Toxoplasmosis in Serbia: time for an action plan.
AB  - Known for a century, Toxoplasma gondii has been studied in Serbia half this time,
      ever since the introduction of the Sabin-Feldman test at the Institute for
      Medical Research (IMR) in 1959. However, despite 50 years of continuous efforts,
      exact data on the frequency of acute clinical disease, acute infections in
      pregnancy and congenital infection in the offspring are still lacking, due to the
      vague regulatory provision that toxoplasmosis is subject to reporting "in case of
      epidemiological indications". It is, however, clear that the major Toxoplasma
      induced public health issue in Serbia, like elsewhere in Europe, is congenital
      toxoplasmosis (CT). Continuous monitoring of particular patient groups showed a
      dramatic decrease in the prevalence of infection over the past two decades, and a
      consequently increased proportion of women susceptible to infection in pregnancy,
      suggesting a potential increase in the incidence of CT. Studies of risk factors
      for infection transmission have provided data to guide national health education
      campaigns. It is expected that the recent appointment of the National Reference
      Laboratory for Toxoplasmosis as the focal point for the collection of data from
      the primary level, will provide the means for accurate assessment of the measure
      of the problem, which is a prerequisite of an evidence-based nation-wide
      prevention program. In the meantime, health education of all pregnant women,
      focused at risk factors of major local significance, is advocated as a sound and
      financially sustainable option to reduce congenital toxoplasmosis.

PMID- 21073141
TI  - Human trichinellosis in Hungary from 1965 to 2009.
AB  - Human trichinellosis was first documented in Hungary in 1891 and then there were
      an increased number of reports up to 1964 when the most severe outbreak occurred.
      After that, no information was available on the international literature on human
      trichinellosis which occurred from 1965 up to the present years. The aim of this
      study was to collect all the data available in Hungarian official data-sources on
      human trichinellosis which occurred from 1965 up to 2009 in Hungary. Furthermore,
      a comparative analysis was performed on the different serological tests used
      along the 45 years of investigation. In the period in question, 573 infections
      were documented in Hungary. Of them, 57 occurred in the years 1965-69, 130 in
      1970-79, 302 in 1980-89, 27 in 1990-99, and 57 in 200009. The most common sources
      of infection were pork from backyard pigs and hunted wild boars. Sporadic cases
      and small family outbreaks marked the last ten years. The comparison of
      serological tests shows that the ELISA is a good test for the first screening,
      but ELISA-positive serum samples should be confirmed by western blot except for
      clinically clear-cut cases.

PMID- 21073142
TI  - Seasonality of trichinellosis in patients hospitalized in Belgrade, Serbia.
AB  - A retrospective study of the course and outcome of trichinellosis in a series of
      50 patients hospitalized at the Institute for Infectious and Tropical Diseases in
      Belgrade between 2001 and 2008 was performed. Clinical diagnosis of
      trichinellosis was based upon the patients' clinical history, symptoms and signs,
      and eosinophilia. The occurrence of cases showed a strong seasonality (P <
      0.0001). The incubation period ranged between one and 33 days. The mean time
      between onset of symptoms and admission was nine days. Family outbreaks were the
      most frequent. Smoked pork products were the dominant source of infection (76%).
      Fever was the most frequent clinical manifestation (90%), followed by myalgia
      (80%) and periorbital edema (76%). 43 patients were examined serologically and
      72% of them had anti-Trichinella antibodies. Eosinophilia and elevated levels of
      serum CK and LDH were detected in 94, 50 and 56% of the patients, respectively.
      All patients responded favorably to treatment with mebendazole or albendazole,
      but eight developed transient complications. Trichinellosis remains a major
      public health issue in Serbia.

PMID- 21073143
TI  - Cystic echinococcosis in Greece. Past and present.
AB  - Cystic echinococcosis is a zoonotic disease with a wide geographical
      distribution, Greece included, and is considered to be a serious problem for the
      public health and the livestock economy. Although the disease was widespread in
      Greece since ancient times, cystic echinococcosis was identified as a serious
      problem around 1970, and since then national surveillance programmes are running,
      based on meat inspection and stray dogs management. Ever since, there are
      official records of the parasite's prevalence in humans and livestock which show
      a continuous decline. More precisely, human hydatidosis, according to the
      official records, declines from an annual incidence of 14.8 per 100,000
      inhabitants during 1967-1971 to 0.3 in 2008. Late surveys reveal that in Greece
      the prevalence of echinococcosis was 23-39.2% for sheep, 7.6-14.7% for goats, 0%
      in cattle and 0.6% in pigs, while further molecular analyses in Southern Greece
      showed the existence of the genotypes G1 and G3 in sheep and G7 in goats in that
      area. All data presented demonstrate that the parasite is still present in
      Greece. Surveillance is nowadays being performed under EU regulations but it is
      highly important to improve and adopt corrective and preventive measures to avoid
      animal and human infection.

PMID- 21073145
TI  - Epidemiology and clinical relevance of Pneumocystis jirovecii Frenkel, 1976
      dihydropteroate synthase gene mutations.
AB  - A review was conducted to examine the published works that studied the prevalence
      of Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations in patients
      with P. jirovecii pneumonia (PcP), in develop and developing countries, and that
      focused the problem of the possible association of these mutations with exposure
      to sulpha or sulphone drugs and their influence in the PcP outcome. Studies
      conducted in United States of America presented higher P. jirovecii mutations
      rates, in comparison with European countries, and in developing countries, lower
      rates of DHPS mutations were reported, due to limited use of sulpha drugs. A
      significant association was reported between the use of sulpha or sulphone agents
      for PcP prophylaxis in HIV-infected patients and the presence of DHPS mutations.
      However these mutations were also detected in PcP patients who were not currently
      receiving sulpha or sulphone agents. The outcome and mortality of HIV-infected
      patients with PcP harbouring DHPS gene mutations were related primarily to the
      underlying severity of illness and the initial severity of PcP, more than to the
      presence of mutations.

PMID- 21073144
TI  - Coexistence of emerging bacterial pathogens in Ixodes ricinus ticks in Serbia.
AB  - The list of tick-borne pathogens is long, varied and includes viruses, bacteria,
      protozoa and nematodes. As all of these agents can exist in ticks, their co
      infections have been previously reported. We studied co-infections of emerging
      bacterial pathogens (Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum
      and Francisella tularensis) in Ixodes ricinus ticks in Serbia. Using PCR
      technique, we detected species-specific sequences, rrf-rrl rDNA intergenic spacer
      for B. burgdorferi s.l., p44/msp2 paralogs for A. phagocytophilum, and the 17 kDa
      lipoprotein gene, TUL4, for F. tularensis, respectively, in total DNA extracted
      from the ticks. Common infections with more than one pathogen were detected in 42
      (28.8%) of 146 infected I. ricinus ticks. Co-infections with two pathogens were
      present in 39 (26.7%) of infected ticks. Simultaneous presence of A.
      phagocytophilum and different genospecies of B. burgdorferi s.l. complex was
      recorded in 16 ticks, co-infection with different B. burgdorferi s. l.
      genospecies was found in 15 ticks and eight ticks harbored mixed infections with
      F. tularensis and B. burgdorferi s.l. genospecies. Less common were triple
      pathogen species infections, detected in three ticks, one infected with A.
      phagocytophilum / B. burgdorferi s.s. / B. lusitaniae and two infected with F.
      tularensis / B. burgdorferi s.s. / B. lusitaniae. No mixed infections of A.
      phagocytophilum and F. tularensis were detected.

PMID- 21073146
TI  - Prevalence and site preferences of heterophyid metacercariae in Tilapia zilli
      from Ismalia fresh water canal, Egypt.
AB  - Factors affecting prevalence and site preferences of heterophyid metacercariae
      (MC) were investigated in this study. A total of 173 specimens of a freshwater
      fish, Tilapia zilli were collected during autumn 2008, winter 2009 and summer
      2009, from Ismailia fresh water canal, Egypt. Results showed that the total
      prevalence of heterophyid MC was 95.37%. The heterophyid MC consisted of
      Haplorchis yokogawi (47.4%), Pygidiopsis genata (21.4%), and Phagicola ascolonga
      (93.64%). H. yokogawi MC was detected in striated muscles, P. ascolonga in liver
      and kidney while, P. genata was detected in muscles, liver and kidney. The
      aggregation indices showed that all MC were aggregated and the P. genata was the
      most highly aggregated followed by H. yokogawi and then P. ascolonga. Responses
      of the heterophyid MC to host sex, weight and season greatly varied according to
      species of MC. Different responses of interaction for heterophyid MC intensity
      were found by GLIM analysis and this variation dependant on the type of infection
      (single or mixed infections). Factors affecting site preference of heterophid MC
      infection were discussed and further studies in other locations are required to
      examine the factors affecting site preference.

PMID- 21073147
TI  - Radix natalensis (Gastropoda: Lymnaeidae), a potential intermediate host of
      Fasciola hepatica in Egypt.
AB  - Experimental infections of Egyptian Radix natalensis with French miracidia of
      Fasciola hepatica were carried out to determine if this snail might act as an
      intermediate host in the life cycle of this digenean in Egypt. Single exposures
      of R. natalensis to miracidia (2/snail) and two successive exposures (a total of
      4 miracidia/ snail) were performed using lymnaeids measuring 1 to 6 mm in height.
      Live larval forms of F. hepatica were noted in single- and double-exposed snails.
      In double exposures, a significant increase of snail survival on day 28 post
      exposure (at 24 degrees C) and an decrease in prevalence were noted when the
      height of snails at exposure was increasing. Cercariae of F. hepatica were shed
      by these snails (90.7/snail) during a mean patent period of 24.3 days. All snails
      have released these cercariae during 2-13 waves of shedding. According to these
      results, R. natalensis can be considered a potential intermediate host of F.
      hepatica in Egypt.

PMID- 21073148
TI  - The prevalence of African animal trypanosomoses and tsetse presence in Western
      Senegal.
AB  - In 2005, the Government of Senegal initiated a tsetse eradication campaign in the
      Niayes and La Petite Cote aiming at the removal of African Animal Trypanosomosis
      (AAT), which is one of the main constraints to the development of more effective
      cattle production systems. The target area has particular meteorological and
      ecological characteristics that provide great potential for animal production,
      but it is unfortunately still infested by the riverine tsetse species Glossina
      palpalis gambiensis Vanderplank (Diptera: Glossinidae). The tsetse project in
      Senegal has adopted an area-wide integrated pest management (AW-IPM) approach
      that targets the entire tsetse population within a delimited area. During the
      first phase of the programme, a feasibility study was conducted that included the
      collection of entomological, veterinary, population genetics, environmental and
      socioeconomic baseline data. This paper presents the parasitological and
      serological prevalence data of AAT in cattle residing inside and outside the
      tsetse-infested areas of the target zone prior to the control effort. At the herd
      level, a mean parasitological prevalence of 2.4% was observed, whereas a
      serological prevalence of 28.7%, 4.4%, and 0.3% was obtained for Trypanosoma
      vivax, T. congolense and T. brucei brucei, respectively. The observed infection
      risk was 3 times higher for T. congolense and T. vivax in the tsetse-infested
      than in the assumed tsetse-free areas. Moreover, AAT prevalence decreased
      significantly with distance from the nearest tsetse captured which indicated that
      cyclical transmission of the parasites by tsetse was predominant over mechanical
      transmission by numerous other biting flies present. The importance of these
      results for the development of a control strategy for the planned AW-IPM campaign
      is discussed.

PMID- 21073149
TI  - MALDI ion trap mass spectrometer with charge detector for large biomolecule
      detection.
AB  - Up to now, all commercial matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometers still can not efficiently analyze very large biomolecules. In
      this work, we report the development of a novel MALDI ion trap mass spectrometer
      which can enrich biomolecular ions to enhance the detection sensitivity. A charge
      detector was installed to measure the large ions directly. With this design, we
      report the first measurement of IgM with the mass-to-charge ratio (m/z) at 980
      000. In addition, quantitative measurements of the number of ions can be
      obtained. A step function frequency scan was first developed to get a clear
      signal in the m/z range from 200,000 to 1,000,000.

PMID- 21073150
TI  - Novel small molecule inhibitors of MDR Mycobacterium tuberculosis by NMR fragment
      screening of antigen 85C.
AB  - Protein target-based discovery of novel antibiotics has been largely unsuccessful
      despite rich genome information. Particularly in need are new antibiotics for
      tuberculosis, which kills 1.6 million people annually and shows a rapid increase
      in multiple-drug-resistant cases. By combining fragment-based drug discovery with
      early whole cell antibacterial screening, we discovered novel ligand-efficient
      inhibitors of multiple-drug resistant Mycobacterium tuberculosis (Mtb), which
      bind to the substrate site of the Mtb protein antigen 85C, hitherto unused in Mtb
      chemotherapy. 

PMID- 21073151
TI  - C72Cl4: a pristine fullerene with favorable pentagon-adjacent structure.
AB  - A long-sought empty non-IPR fullerene, (#11188)C72, which is more stable than the
      sole IPR isomer in the fullerene[72] family, has been retrieved and
      crystallographically characterized as (#11188)C72Cl4. Mass spectrometric data
      support the facile dechlorination of (#11188)C72Cl4 and, in turn, the possible
      stability of pristine (#11188)C72.

PMID- 21073152
TI  - Polyhedral 50-facet Cu2O microcrystals partially enclosed by {311} high-index
      planes: synthesis and enhanced catalytic CO oxidation activity.
AB  - Micro- and nanoparticles with high-index facets may exhibit higher chemical
      activities that are of great importance in practical applications. Cuprite is a
      potential alternative to expensive noble metals as the catalyst for CO oxidation
      at moderate temperatures. We report here a solution based approach to the
      preparation of unusual polyhedral 50-facet Cu2O microcrystals with a
      morphological yield higher than 70%. It has been revealed that the concentration
      of OH(-) and the volume ratio of polar organic solvent to water in the mixed
      solvent play crucial roles in controlling the morphology of Cu2O microcrystals.
      The formation of the 50 facets could be geometrically viewed as the truncation of
      all the 24 vertices of a small rhombicuboctahedron having 26 facets. When growing
      from solutions, however, the anisotropic growth rates along the <100>, <110>, and
      <111> directions might be responsible for the formation of this morphology. The
      Miller index of the 24 nearly isosceles trapezoids could be assigned to {311}
      planes based on geometrical analysis and was verified by simulated models using
      the WinXmorph software and supported by TEM and ED observations. Compared with
      other polyhedral Cu2O microcrystals, the as-prepared microcrystals showed a
      higher specific catalytic rate toward CO oxidation.

PMID- 21073153
TI  - Cooperative melting in caged dimers with only two DNA duplexes.
AB  - Small molecule-DNA hybrids with only two parallel DNA duplexes (rSMDH2) displayed
      sharper melting profiles compared to unmodified DNA duplexes, consistent with
      predictions from neighboring-duplex theory. Using adjusted thermodynamic
      parameters obtained from a coarse-grain dynamic simulation, the experimental data
      fit well to an analytical model.

PMID- 21073154
TI  - Adsorption kinetics of laponite and ludox silica nanoparticles onto a deposited
      poly(diallyldimethylammonium chloride) layer measured by a quartz crystal
      microbalance and optical reflectometry.
AB  - A quartz crystal microbalance with dissipation (QCM-D) and an optical
      reflectometer (OR) have been used to investigate the adsorption behavior of
      Laponite and Ludox silica nanoparticles at the solid-liquid interface. The
      adsorption of both Laponite and Ludox silica onto poly(diallyldimethylammonium
      chloride) (PDADMAC)-coated surfaces over the first few seconds were studied by
      OR. Both types of nanoparticles adsorbed rapidly and obtained a stable adsorbed
      amount after only a few minutes. The rate of adsorption for both nanoparticle
      types was concentration dependent. The maximum adsorption rate of Ludox
      nanoparticles was found to be approximately five times faster than that for
      Laponite nanoparticles. The QCM data for the Laponite remained stable after the
      initial adsorption period at each concentration tested. The observed plateau
      values for the frequency shifts increased with increasing Laponite particle
      concentration. The QCM data for the Ludox nanoparticles had a more complex long
      time behavior. In particular, the dissipation data at 3 ppm and 10 ppm Ludox
      increased slowly with time, never obtaining a stable value within the duration of
      the experiment. We postulate here that this is caused by slow structural
      rearrangements of the particles and the PDADMAC within the surface adsorbed
      layer. Furthermore, the QCM dissipation values were significantly smaller for
      Laponite when compared with those for Ludox for all nanoparticle concentrations,
      suggesting that the Laponite adsorbed layer is more compact and more rigidly
      bound than the Ludox adsorbed layer.

PMID- 21073155
TI  - Dynamic study of nanodroplet nucleation and growth on self-supported nanothick
      liquid films.
AB  - The dynamics of water condensation on self-supported thin films was studied at
      the nanoscale using transmitted electrons in an environmental scanning electron
      microscope. The initial stages of nucleation and growth over nanothick water
      films have been investigated. Irregularities at the water-film boundaries
      constituted nucleation sites for asymmetric dropwise and filmwise condensation.
      Nanodroplet growth was associated with center of mass movement, and the dynamic
      growth power law dependence was explored for the nanoscale.

PMID- 21073156
TI  - Acid-catalyzed and solvolytic desulfation of H2SO4-hydrolyzed cellulose
      nanocrystals.
AB  - Cellulose nanocrystals (CNCs) prepared by H(2)SO(4) hydrolysis have sulfate
      groups on their surface, which have negative implications for some CNC
      applications. In this study, two desulfation methods were evaluated, and the
      properties of desulfated CNCs were compared to those of unsulfated CNCs, prepared
      by HCl hydrolysis. H(2)SO(4)-hydrolyzed CNCs from softwood sulfite pulp were
      subjected to either a mild acid hydrolytic desulfation or a solvolytic
      desulfation in dimethyl sulfoxide via the pyridinium salt. Removal of the sulfate
      groups was confirmed by conductometric titration and X-ray photoelectron
      spectroscopy. The effect of the desulfation procedure on the lateral crystallite
      dimensions was analyzed by X-ray diffraction. The extent of particle aggregation
      in the samples was assessed by atomic force microscopy and dynamic light
      scattering. The acid hydrolytic method achieved only partial desulfation and
      produced gradually decreasing sulfate contents upon successive repetition. The
      solvolytic method achieved nearly complete desulfation in a single step. The
      desulfated CNCs showed similar particle aggregation as the HCl-hydrolyzed CNCs,
      but the extent of aggregation was slightly less.

PMID- 21073157
TI  - Stabilizing G-quadruplex DNA by a scissors-shaped binaphthyl derivative through
      the entangling mode: cooperation of binaphthylene and the ethoxy chain.
AB  - A scissors-shaped binaphthyl derivative (NPA) has been found to stabilize the G
      quadruplex by intertwisting the whole G-quadruplex with two long chains, through
      the cooperation of the two functional groups: binaphthylene and the ethoxy chain.
      Moreover, NPA exhibits a good inhibitory effect of telomerase activity as well as
      excellent cytotoxic activity against HepG-2 human liver cancer cells.

PMID- 21073158
TI  - Hybrid inorganic-organic adsorbents Part 1: Synthesis and characterization of
      mesoporous zirconium titanate frameworks containing coordinating organic
      functionalities.
AB  - A series of functional hybrid inorganic-organic adsorbent materials have been
      prepared through postsynthetic grafting of mesoporous zirconium titanate xerogel
      powders using a range of synthesized and commercial mono-, bis-, and tris
      phosphonic acids, many of which have never before been investigated for the
      preparation of hybrid phases. The hybrid materials have been characterized using
      thermogravimetric analysis, diffuse reflectance infrared (DRIFT) and 31P MAS NMR
      spectroscopic techniques and their adsorption properties studied using a 153Gd
      radiotracer. The highest level of surface functionalization (molecules/nm2) was
      observed for methylphosphonic acid (~3 molecules/nm2). The level of
      functionalization decreased with an increase in the number of potential surface
      coordinating groups of the phosphonic acids. Spectral decomposition of the DRIFT
      and 31P MAS NMR spectra showed that each of the phosphonic acid molecules
      coordinated strongly to the metal oxide surface but that for the 1,1-bis
      phosphonic acids and tris-phosphonic acids the coordination was highly variable
      resulting in a proportion of free or loosely coordinated phosphonic acid groups.
      Functionalization of a porous mixed metal oxide framework with the tris
      methylenephosphonic acid (ATMP-ZrTi-0.33) resulted in a hybrid with the highest
      affinity for 153Gd3+ in nitric acid solutions across a wide range of acid
      concentrations. The ATMP-ZrTi-0.33 hybrid material extracted 153Gd3+ with a Kd
      value of 1*10(4) in 0.01 M HNO3 far exceeding that of the other hybrid phases.
      The unfunctionalized mesoporous mixed metal oxide had negligible affinity for
      Gd3+ (Kd<100) under identical experimental conditions. It has been shown that the
      presence of free or loosely coordinated phosphonic acid groups does not
      necessarily translate to affinity for 153Gd3+. The theoretical cation exchange
      capacity of the ATMP-ZrTi-0.33 hybrid phase for Gd3+ has been determined to be
      about 0.005 mmol/g in 0.01 M HNO3. This behavior and that of the other hybrid
      phases suggests that the surface-bound ATMP ligand functions as a chelating
      ligand toward 153Gd3+ under these acidic conditions.

PMID- 21073159
TI  - Depletion interactions effected by different variants of fd virus.
AB  - The depletion interaction between a probe sphere and a flat wall induced by fd
      virus is investigated by means of total internal reflection microscopy (TIRM).
      The viruses serve as a model system for monodisperse, rod-like colloids. We find
      that the experimental potentials are well described by the first-order density
      approximation up to an fd content of several overlap concentrations. This is in
      accordance with higher order density theory as confirmed by numerical
      calculations. Since the first-order analytical description still holds for all
      measurements, this exemplifies that higher order terms of the theory are
      unimportant for our system. Comparing the potentials induced by wild-type fd to
      those induced by a more rigid fd variant, it can be shown that the influence of
      the virus stiffness is beyond our experimental resolution and plays only a
      negligible role for the measured depletion potentials.

PMID- 21073160
TI  - Non-natural macrocyclic inhibitors of histone deacetylases: design, synthesis,
      and activity.
AB  - Nonpeptidic chiral macrocycles were designed on the basis of an analogue of
      suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11
      histone deacetylase (HDAC) isoforms. The identification of critical amino acid
      residues highly conserved in the cap region of HDACs guided the design of the
      suberoyl-based macrocycles, which were expected to bear a maximum common
      substructure required to target the whole HDAC panel. A nanomolar HDAC inhibitory
      profile was observed for several compounds, which was comparable, if not
      superior, to that of 2. A promising cytotoxic activity was found for selected
      macrocycles against lung and colon cancer cell lines. Further elaboration of
      selected candidates led to compounds with an improved selectivity against HDAC6
      over the other isozymes. Pair-fitting analysis was used to compare one of the
      best candidates with the natural tetrapeptide apicidin, in an effort to define a
      general pharmacophore that might be useful in the design of surrogates of
      peptidic macrocycles as potent and isoform-selective inhibitors. 

PMID- 21073161
TI  - Patterning of quantum dot bioconjugates via particle lithography.
AB  - We present a simple technique to fabricate hexagonally ordered quantum dot
      bioconjugate (QDBC) dot arrays on glass coverslips. We used particle lithography
      to create periodic holes in a layer of methoxy-poly(ethylene glycol)-silane and
      then adsorbed QDBCs into the holes. To demonstrate the versatility of this
      technique, we made separate periodic arrays of quantum dots (QDs) conjugated to
      three different biologically important molecules: biotin, streptavidin, and anti
      mouse IgG. The diameters of the regions where the QDBCs adsorbed were 500-600 nm
      and independent of the QDBC patterned. The site density of the QDBCs in the
      patterned holes could be varied by simply adjusting the coating concentration of
      the QDBC solution. We demonstrate the applicability of these substrates by
      designing a QDBC-based binding assay with a working concentration range of
      several orders of magnitude and a sub-picomolar detection limit.

PMID- 21073162
TI  - Superamphiphilic Janus fabric.
AB  - Janus fabrics with superamphiphilicity were fabricated via electrospinning of
      polyacrylonitrile (PAN). PAN nanofibrous mats were formed on an aluminum foil
      substrate and then thermally treated to cause hydrolysis. An identical PAN
      solution was subsequently electrospun onto the hydrolyzed PAN layer, followed by
      peeling off of the bicomposite film from the collector substrate to produce a
      free-standing Janus fabric. On one side, the electrospun PAN mat exhibited
      superhydrophobic properties, with a water contact angle of 151.2 degrees ,
      whereas the initially superhydrophobic PAN sheet on the opposite side of the
      fabric was converted to a superhydrophilic surface (water contact angle of 0
      degrees ) through hydrolysis of the surface functional groups induced by the
      thermal treatment. The resulting Janus fabrics exhibited both
      superhydrophobicity, repelling water on the one side, and superhydrophilicity,
      absorbing water on the other side. The organic solvent resistance of the PAN
      nanofibrous sheets was remarkably improved by incorporation of a tetraethyl
      orthosilicate. This facile and simple technique introduces a new route for the
      design and development of functional smart, robust fabrics from an inexpensive,
      commercially available polymer.

PMID- 21073163
TI  - Comparison of ultrasonic distillation to sparging of liquid mixtures.
AB  - The application of intense ultrasound to a liquid-gas interface results in the
      formation of an ultrasonic fountain and generates both mist and vapor from the
      liquid. Here, the composition of the vapor and aerosol above an ultrasonic
      fountain is determined as a function of irradiation time and compared with the
      results of sparging for five different solutions. The experimental apparatus for
      determining the efficiency of separation consists of a glass vessel containing a
      piezoelectric transducer driven at either 1.65 or 2.40 MHz. Dry nitrogen is
      passed over the ultrasonic fountain to remove the vapor and aerosol. The
      composition of the liquid solutions are recorded as a function of irradiation
      time using gas chromatography, refractive index measurement, nuclear magnetic
      resonance, or spectrophotometry. Data are presented for ethanol-water and ethyl
      acetate-ethanol solutions, cobalt chloride in water, colloidal silica, and
      colloidal gold. The experiments show that ultrasonic distillation produces
      separations that are somewhat less complete than what is obtained using sparging.

PMID- 21073164
TI  - Selenium-modified TiO2 and its impact on photocatalysis.
AB  - This work describes the preparation of a selenium-modified TiO(2) photocatalyst
      and a preliminary evaluation of its photocatalytic activity. Se-TiO(2) displayed
      greater visible absorption than undoped TiO(2) and was still capable of degrading
      quinoline at a slightly faster rate than undoped TiO(2) under UV light. Se-TiO(2)
      was also able to degrade organic molecules under purely visible light by a single
      electron transfer pathway. Irradiation with >435 nm light showed no evidence of
      efficient production of HO*-like species. Se-TiO(2) was also examined under
      hypoxic conditions, where the Se atoms were capable of trapping photogenerated
      electrons as evidenced by XPS.

PMID- 21073165
TI  - Speciated human high-density lipoprotein protein proximity profiles.
AB  - It is expected that the attendant structural heterogeneity of human high-density
      lipoprotein (HDL) complexes is a determinant of its varied metabolic functions.
      To determine the structural heterogeneity of HDL, we determined major
      apolipoprotein stoichiometry profiles in human HDL. First, HDL was separated into
      two main populations, with and without apolipoprotein (apo) A-II, LpA-I and LpA
      I/A-II, respectively. Each main population was further separated into six
      individual subfractions using size exclusion chromatography (SEC). Protein
      proximity profiles (PPPs) of major apolipoproteins in each individual subfraction
      was determined by optimally cross-linking apolipoproteins within individual
      particles with bis(sulfosuccinimidyl) suberate (BS(3)), a bifunctional cross
      linker, followed by molecular mass determination by MALDI-MS. The PPPs of LpA-I
      subfractions indicated that the number of apoA-I molecules increased from two to
      three to four with an increase in the LpA-I particle size. On the other hand, the
      entire population of LpA-I/A-II demonstrated the presence of only two proximal
      apoA-I molecules per particle, while the number of apoA-II molecules varied from
      one dimeric apoA-II to two and then to three. For most of the PPPs described
      above, an additional population that contained a single molecule of apoC-III in
      addition to apoA-I and/or apoA-II was detected. Upon composition analyses of
      individual subpopulations, LpA-I/A-II exhibited comparable proportions for total
      protein (~58%), phospholipids (~21%), total cholesterol (~16%), triglycerides
      (~5%), and free cholesterol (~4%) across subfractions. LpA-I components, on the
      other hand, showed significant variability. This novel information about HDL
      subfractions will form a basis for an improved understanding of particle-specific
      functions of HDL.

PMID- 21073166
TI  - Regenerable and simultaneous surface plasmon resonance detection of abeta(1-40)
      and abeta(1-42) peptides in cerebrospinal fluids with signal amplification by
      streptavidin conjugated to an N-terminus-specific antibody.
AB  - A major constituent in the deposit of the brain in a patient with Alzheimer's
      disease (AD) is the aggregates/fibrils of amyloid-beta (Abeta) peptides
      containing 39-43 amino acids. The total Abeta levels and the concentration ratio
      between the most abundant Abeta(1-40) peptide and the more aggregation-prone
      Abeta(1-42) in body fluids (e.g., cerebrospinal fluid or CSF) have been suggested
      as possible criteria for early diagnosis of AD. By immobilizing capture
      antibodies specific to the two peptides in separate fluidic channels, surface
      plasmon resonance (SPR) has been used to quantify Abeta(1-40) and Abeta(1-42)
      present in CSF samples collected from AD patients and healthy donors. With signal
      amplification by streptavidin conjugated to an antibody that is selective to the
      common N-terminus of the Abeta peptides, concentrations as low as 20 pM can be
      readily measured. The range of Abeta peptide concentrations measurable by this
      method spans 4 orders of magnitude. The ability of regenerating the sensor
      surface for repeated measurements not only improves the reproducibility but also
      enhances the sample throughput. Our data reveal that the ratio of Abeta(1-40)
      concentration versus Abeta(1-42) concentration in CSF samples from AD patients is
      almost twice as high as that from healthy persons. In contrast to the commonly
      used enzyme-linked immunosorbent assay (ELISA), SPR obviates the need of a more
      expensive and less stable enzyme conjugate and the use of carcinogenic substrate
      for the signal detection and allows the binding events to be monitored in real
      time.

PMID- 21073167
TI  - A study of the evolution of inverted-topology repeats from LeuT-fold transporters
      using AlignMe.
AB  - X-ray crystal structures have revealed that numerous secondary transporter
      proteins originally categorized into different sequence families share similar
      structures, namely, the LeuT fold. The core of this fold consists of two units of
      five transmembrane helices, whose conformations have been proposed to exchange to
      form the two alternate states required for transport. That these two units are
      related implies that LeuT-like transporters evolved from gene-duplication and
      fusion events. Thus, the origins of this structural repeat may be relevant to the
      evolution of transport function. However, the lack of significant sequence
      similarity requires sensitive sequence search methods for analyzing their
      evolution. To this end, we developed a software application called AlignMe, which
      can use various types of input information, such as residue hydrophobicity, to
      perform pairwise alignments of sequences and/or of hydropathy profiles of
      (membrane) proteins. We used AlignMe to analyze the evolutionary relationships
      between repeats of the LeuT fold. In addition, we identified proteins from the so
      called DedA family that potentially share a common ancestor with these repeats.
      DedA domains have been implicated in, e.g., selenite uptake; they are found
      widely distributed across all kingdoms of life; two or more DedA domains are
      typically found per genome, and some may adopt dual topologies. These results
      suggest that DedA proteins existed in ancient organisms and may function as
      dimers, as required for a would-be ancestor of the LeuT fold. In conclusion, we
      provide novel insights into the evolution of this important structural motif and
      thus potentially into the alternating-access mechanism of transport itself.

PMID- 21073168
TI  - Hydrogen bond partner reorganization in the coadsorption of a monodendron and
      pyridylethynyl derivatives.
AB  - Hydrogen bonds with high selectivity and directionality are significant in
      harnessing molecules to form 2D supramolecular nanostructures. The competition
      and reorganization of hydrogen bond partners determine the ultimate molecular
      assembly and pattern in a 2D supramolecular system. In this study, multicomponent
      assemblies of a monodendron (5-benzyloxy-isophthalic acid derivative, BIC) and
      pyridylethynyl derivatives [1,4-bis(4-pyridylethynyl)-2,3-bis-dodecyloxy-benzene
      (PBPC12) and 1,4-bis(4-pyridylethynyl)-2,3-bis-octadecyloxy-benzene (PBPC18)]
      have been studied by scanning tunneling microscopy (STM) on a graphite surface.
      BIC molecules are able to associate with PBPC12 and PBPC18 molecules to induce
      the rearrangement of hydrogen bond partners and form coassembly structures.
      Interestingly, BIC acts as a template molecule in the coassembly process, and
      these multicomponent structures exhibit similar structural features to the
      assembly structures of BIC itself. The structural details of the coassembled
      structures are revealed by high-resolution STM images, and their relationship
      with the original BIC assemblies is discussed. These results provide important
      insights into the design and fabrication of hydrogen-bond-directed multicomponent
      molecular nanostructures on solid surfaces.

PMID- 21073169
TI  - Comparative study of the usefulness of low energy Cs(+), Xe(+), and O(2)(+) ions
      for depth profiling amino-acid and sugar films.
AB  - This work reports a comparative study on the capability of low energy primary ion
      beams for depth profiling nonpolymeric molecules including amino-acid and sugar
      layers. Due to their different behavior regarding depth profiling, phenylalanine
      and trehalose molecules are chosen as reference systems. Each molecule was
      dissolved in suitable solvent prior to spin-coating on clean silicon wafer. The
      film thicknesses were in the order of 70 and 100 nm for phenylalanine and
      trehalose respectively. Depth profiling feasibility were assessed first using
      Cs(+) as reactive sputtering ion at various energies. The results obtained under
      Cs(+) sputtering ions are compared afterward to those obtained under Xe(+)
      sputtering ions which are inert and have a mass very similar to Cs(+). In order
      to investigate the effect of oxygen, depth profiling are also performed using
      either Xe(+) under oxygen flooding or O(2)(+) as sputtering ions. While
      phenylalanine could be depth profiled successfully using Cs(+) ions, Xe(+) and
      O(2)(+) ions failed to retain any characteristic signal. The sputtering yields
      measured as a function of the ion beam energies were higher using Cs(+), in
      particular at low energies. The chemical reactivity of the cesium atoms being
      implanted during the sputtering process helps to prevent the loss of the
      molecular phenylalanine signal. In contrast, depth profiling of trehalose was
      more successful upon Xe(+) and O(2)(+) compared to Cs(+). In this case the
      sputtering yields were higher if Xe(+) primary ion is employed instead of Cs(+).
      The different trends observed in this study are interpreted using arguments
      involving the reactivity of the sputtering ions.

PMID- 21073170
TI  - Radiofluorinated rhenium cyclized alpha-MSH analogues for PET imaging of
      melanocortin receptor 1.
AB  - In order to accomplish in vivo molecular imaging of melanoma biomarker
      melanocortin 1 receptor (MC1R), several alpha-melanocyte-stimulating hormone
      (alpha-MSH) analogues have been labeled with N-succinimidyl-4-18F-fluorobenzoate
      (18)F-SFB) and studied as positron emission tomography (PET) probes in our recent
      studies. To further pursue a radiofluorinated alpha-MSH peptide with high
      clinical translation potential, we utilized 4-nitrophenyl 2-18F-fluoropropionate
      (18F-NFP) to radiofluorinate the transition metal rhenium cyclized alpha-MSH
      metallopeptides for PET imaging of MC1R positive malignant melanoma.
      Metallopeptides Ac-d,Lys-ReCCMSH(Arg11) (two isomers, namely RMSH-1 and RMSH-2)
      were synthesized using conventional solid phase peptide synthesis chemistry and
      rhenium cyclization reaction. The two isomers were then conjugated with 19F-NFP
      or 18F-NFP. The resulting cold or radiofluorinated metallopeptides, (18/19)F-FP
      RMSH-1 and (18/19)F-FP-RMSH-2, were further evaluated for their in vitro receptor
      binding affinities, in vivo biodistribution, and small-animal PET imaging
      properties. The binding affinities of 19F-FP-RMSH-1 and 19F-FP-RMSH-2 were
      determined to be within low nanomolar range. In vivo studies revealed that both F
      labeled metallopeptides possessed good tumor uptake in the B16F10 murine model
      with high MC1R expression, while possessing much lower uptake in A375M human
      melanoma xenografts. Moreover, 18F-FP-RMSH-1 displayed more favorable in vivo
      performance in terms of higher tumor uptake and much lower accumulation in the
      kidney and liver, when compared to that of 18F-FP-RMSH-2 at 2 h postinjection
      (p.i.). 18F-FP-RMSH-1 also displayed lower liver and lung uptake when compared
      with that of the same peptide labeled with 18F-SFB (named as 18F-FB-RMSH-1).
      Small animal PET imaging of 18F-FP-RMSH-1 in mice bearing B16F10 tumors at 1 and
      2 h showed good tumor imaging quality. As expected, much lower tumor uptake and
      poorer tumor/normal organ contrast were observed for A375M model compared to
      those of the B16F10 model. 18F-FP-RMSH-1 also exhibited higher tumor uptake and
      better tumor retention when compared with 18F-FB-RMSH-1. 18F-FP-RMSH-1
      demonstrates significant advantages over 18F-FB-RMSH-1 and 18F-FP-RMSH-2. It is a
      promising PET probe for imaging MC1R positive melanoma and MC1R expression in
      vivo.

PMID- 21073172
TI  - Diterpenoid constituents of the roots of Salvia digitaloides.
AB  - Salvia digitaloides, belonging to the economically and medicinally important
      genus Salvia, is distributed in the northwest of Yunnan Province, People's
      Republic of China. The roots of this plant were soaked in alcohol by local
      Tibetans to make a special traditional "red wine", and many local people like to
      drink this traditional "red wine" to strengthen physical health. To investigate
      the bioactive diterpenoid constituents of the roots, a detailed phytochemical
      study was carried out, and 13 diterpenoids including two new norditerpenoids,
      dihydroneotanshinlactone (1) and 16,17-dinorpisferal A (2), were isolated. Their
      structures were established on the basis of detailed spectroscopic analysis. In
      addition, computational methods were applied to validate the stereochemistry of
      compound 1. For the bioassay to inhibit the growth of five tumor cell lines,
      neotanshinlactone (3) exhibited selective cytotoxic activity toward the human
      breast cancer cell line SK-BR-3, while the other four tanshinones (4-7) showed
      significant toxicity effects against all of the tested five cell lines. 

PMID- 21073171
TI  - Improved speciation characteristics of PEGylated indocyanine green-labeled
      Panitumumab: revisiting the solution and spectroscopic properties of a near
      infrared emitting anti-HER1 antibody for optical imaging of cancer.
AB  - A water-soluble amine-reactive PEGylated analogue of near-infrared emitting dye
      indocyanine green (5) was synthesized and used to label the anti-HER1 antibody
      panitumumab (Vectibix) at various equivalents. These conjugates were compared
      with non-PEGylated analogue conjugate products and the solution speciation
      analyzed with UV-vis spectrophotometry, size exclusion HPLC, and SDS-PAGE.
      PEGylation of the bioconjugates was successful in preventing aggregation in
      solution, a phenomenon observed with the non-PEGylated bioconjugates presumably
      due to the hydrophobicity of indocyanine green. Competitive radioimmunoassay
      demonstrated that the targeting moiety of the PEGylated bioconjugates was
      conserved. Fluorescence microscopy also demonstrated membrane binding of the
      bioconjugate to HER1-expressing A431 cells. Hence, these bioconjugates are
      suitable candidates for the in vivo optical imaging of HER1-expressing tumors.

PMID- 21073173
TI  - Time-dependent enzyme activity dominated by dissociation of J-aggregates bound to
      protein surface.
AB  - J-Aggregates of diprotonated 5,10,15,20-tetrakis(4-sulfonatopheny)porphyrin
      (H4TPPS2-) were stabilized even in a neutral aqueous solution (pH 7.0) containing
      per-O-methylated beta-cyclodextrin by binding to the surface of alpha
      chymotrypsin (ChT). The large J-aggregates covered the active site of ChT and
      completely inhibited the hydrolysis of the peptides. However, enzyme activity was
      gradually restored with the dissociation of the J-aggregates attached to the
      protein surface to monomers. After the completion of dissociation of the
      aggregates, the enzyme activity was almost completely restored, though the
      structure of ChT significantly changed. Circular dichroism spectroscopy suggested
      that the microscopic structure at the active site of ChT was scarcely affected by
      the J-aggregates, but the binding of J-aggregates to ChT increased the content of
      the random coils in the enzyme. The present study showed a new type of effector
      for controlling the function of ChT.

PMID- 21073174
TI  - Chromatography using a water stationary phase and a carbon dioxide mobile phase.
AB  - A novel chromatographic separation method is introduced which employs water
      (saturated with CO(2)) as a stationary phase and CO(2) (saturated with water) as
      a mobile phase. Since water and CO(2) have little miscibility, conditions can be
      attained that create a stationary phase of water lining the inside of an uncoated
      stainless steel capillary. Because altering temperature and pressure can change
      both the density of the mobile phase and the polarity of the stationary phase,
      these experimental parameters offer good flexibility for optimizing separations
      and allow for different gradient programmed separation options. Further, since
      this method is free of organic stationary and mobile phase components, it is
      environmentally compatible and allows the use of universal flame ionization
      detection. This system offers very good sample capacity, peak symmetry, and
      retention time reproducibility (~1% RSD run-to-run, ~4% RSD day-to-day). Analytes
      such as alcohols, carboxylic acids, phenols, and tocopherols are employed to
      investigate this relatively inexpensive and robust method. As an application, the
      system is used to quantify ethanol in alcoholic beverages and biofuel and to
      analyze caffeine levels in drinks. In all cases, quantitative results are
      obtained with quick throughput times and often little need for sample
      preparation.

PMID- 21073175
TI  - Ultra performance liquid chromatographic profiling of serum N-glycans for fast
      and efficient identification of cancer associated alterations in glycosylation.
AB  - Glycosylation is a diverse but critically important post-translational
      modification that modulates the physical, chemical and biological properties of
      proteins. Alterations in glycosylation have been noted in a number of diseases
      including cancer. The discovery of alterations in the glycosylation of serum
      glycoproteins which may offer potential as biomarkers is attracting considerable
      research interest. In the current study, the significant improvements in
      efficiency, selectivity, and analysis speed offered by ultra performance liquid
      chromatography (UPLC) profiling of fluorescently labeled N-linked
      oligosaccharides on a recently introduced sub-2 MUm hydrophilic interaction
      (HILIC) based stationary phase are demonstrated to identify cancer associated
      alterations in the serum N-glycome of patients bearing stomach adenocarcinoma.
      The contribution of the glycosylation present on four highly abundant serum
      proteins namely, IgG, haptoglobin, transferrin, and alpha1-acid glycoprotein was
      evaluated. Alterations in the glycosylation present on these four proteins
      isolated from the pathologically staged cancer serum using either affinity
      purification or two-dimensional electrophoresis were then investigated as
      possible markers for stomach cancer progression. In agreement with previous
      reports, an increase in sialylation was observed on haptoglobin, transferrin, and
      alpha1-acid glycoprotein in the cancerous state. Increased levels of core
      fucosylated biantennary glycans and decreased levels of monogalactosylated core
      fucosylated biantennary glycans were present on IgG with increasing disease
      progression. The speed and selectivity offered by the sub-2 MUm HILIC phase make
      it ideal for rapid yet highly efficient separation of complex oligosaccharide
      mixtures such as that present in the serum N-glycome.

PMID- 21073176
TI  - Fabrication and photoelectrochemical characteristics of the patterned CdS
      microarrays on indium tin oxide substrates.
AB  - In an effort to investigate the extraordinary photoelectrochemical
      characteristics of nanostructured CdS thin films in promising photovoltaic device
      applications, the patterned CdS microarrays with different feature sizes (50,
      130, and 250 MUm in diameter) were successfully fabricated on indium tin oxide
      (ITO) glass substrates using the chemical bath deposition method. The ultraviolet
      lithography process was employed for fabricating patterned
      octadecyltrichlorosilane (OTS) self-assembled monolayers (SAMs) as the functional
      organic thin layer template. The results show that the regular and compact
      patterned CdS microarrays had been deposited onto ITO glass surfaces, with clear
      edges demarcating the boundaries between the patterned CdS region and substrate
      under an optimal depositing condition. The microarrays consisted of pure
      nanocrystalline CdS with average crystallite size of about 10.7 nm. The
      photocurrent response and the optical adsorption of the patterned CdS microarray
      thin films increased with the decrease of the feature size, which was due to the
      increased CdS surface area, as well as the increased optical path length within
      the patterned CdS thin films, resulting from multiple reflection of incident
      light. The resistivity values increase with the increase of feature size, due to
      the increase of the relative amount of gaps between CdS microarrays with
      increasing the feature size of patterned CdS microarrays.

PMID- 21073177
TI  - Electrospun carbon nanofibers as low-cost counter electrode for dye-sensitized
      solar cells.
AB  - Electrospun carbon nanofibers (ECNs) have been explored as an electrocatalyst and
      low-cost alternative to platinum (Pt) for triiodide reduction in dye-sensitized
      solar cells (DSCs). The results of electrochemical impedance spectroscopy (EIS)
      and cyclic voltammetry measurements indicated that the ECN counter electrodes
      exhibited low charge-transfer resistance (Rct), large capacitance (C), and fast
      reaction rates for triiodide reduction. Although the efficiency (eta) of ECN
      based cells was slightly lower than that of Pt-based cells, their short circuit
      current density (Jsc) and open circuit voltage (Voc) were comparable. The ECN
      based cells achieved an energy conversion efficiency (eta) of 5.5 % under the AM
      1.5 illumination at 100 mW cm(-2). The reason for lower cell performance using
      the ECN electrode was because of its lower fill factor (FF) than that of Pt-based
      cells, probably caused by high total series resistance (RStot) at ~15.5 Omega
      cm2, which was larger than that of ~4.8 Omega cm2 in the Pt-based devices.
      Simulated results showed that the fill factor (FF) and eta could be substantially
      improved by decreasing RStot, which might be achieved by using thinner and highly
      porous ECNs to reduce the thickness of the ECNs counter electrode.

PMID- 21073178
TI  - Rapid formation of superhydrophobic surfaces with fast response wettability
      transition.
AB  - We have developed a facile and time-saving method to prepare superhydrophobic
      surfaces on copper sheets. Various surface textures composed of Cu(OH)2 nanorod
      arrays and CuO microflowers/Cu(OH)2 nanorod arrays hierarchical structure were
      prepared by a simple solution-immersion process. After chemical modification with
      stearic acid, the wettability of the as-prepared surfaces was changed from
      superhydrophilicity to superhydrophobicity. The shortest processing time for
      fabricating a superhydrophobic surface was 1.5 min. Interestingly, the rapid
      wettability transition between superhydrophobicity and superhydrophilicity can be
      realized on the prepared surfaces with ease by the alternation of air-plasma
      treatment and stearic acid coating. It took just 2 min to complete the whole
      wettability transition. Additionally, the regeneration of the superhydrophobic
      surface is also considered regarding its application.

PMID- 21073179
TI  - Evidence of formation of ammonium perfluorononanoate/2H2O multilamellar vesicles:
      morphological analysis by rheology and rheo-2H NMR experiments.
AB  - Rheology and rheo-(2)H NMR measurements are presented for 30 wt % ammonium
      perfluorononanoate (APFN)/(2)H(2)O mixture in the temperature range 20-70 
      degrees C. A first-order lamellar-to-nematic transition occurs at 42  degrees C,
      and a first-order nematic-to-isotropic transition occurs at 49  degrees C.
      Different rheological behaviors of the lamellar phase were observed with
      increasing the temperature. The lamellar structure at low temperature (Lalpha(-))
      has a clear gel-like viscoelasticity, while at high temperature the lamellar
      structure (Lalpha(+)) has a liquid-like response. In this study we have observed
      for the first time, along with the lamellar phase of a surfactant containing
      fluorinated fatty acid, the formation of multilamellar vesicles (MLVs) ("onions")
      induced by shear. With the aid of nonlinear rheology and rheo-NMR techniques,
      onion formation was found to occur in both temperature regimes of the lamellar
      phase, but at different strain units. It is suggested that the lamellar phase
      consists of smectic structures in both Lalpha(-) and Lalpha(+), but with
      different percentages of defect density.

PMID- 21073180
TI  - Fabrication and characterization of axially doped silicon nanowire tunnel field
      effect transistors.
AB  - Tunnel field-effect transistors were fabricated from axially doped silicon
      nanowire p-n junctions grown via the vapor-liquid-solid method. Following dry
      thermal oxidation to form a gate dielectric shell, the nanowires have a p-n-n(+)
      doping profile with an abrupt n-n(+) junction, which was revealed by scanning
      capacitance microscopy. The lightly doped n-segment can be inverted to p(+) by
      modulating the top gate bias, thus forming an abrupt gated p(+)-n(+) junction. A
      band-to-band tunneling current flows through the electrostatically doped p(+)
      n(+) junction when it is reverse biased. Current-voltage measurements performed
      from 375 down to 4.2 K show two different regimes of tunneling current at high
      and low temperatures, indicating that there are both direct band-to-band and trap
      assisted tunneling paths. 

PMID- 21073181
TI  - Diphenylthiourea, a common rubber chemical, is bioactivated to potent skin
      sensitizers.
AB  - Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a
      vulcanization accelerator in the production of synthetic rubber, for example,
      neoprene. The versatile usage of neoprene is due to the multifaceted properties
      of the material; for example, it is stretchable, waterproof, and chemical- and
      abrasion-resistant. The wide application of neoprene has resulted in numerous
      case reports of dermatitis patients allergic to DPTU. The mechanism by which DPTU
      works as a contact allergen has not been described; thus, the aim of the present
      study was to investigate if DPTU is a prohapten that can be activated by skin
      metabolism. The metabolic activation and covalent binding of (14)C-labeled DPTU
      to proteins were tested using a skinlike cytochrome P450 (P450) cocktail
      containing the five most abundant P450s found in human skin (CYP1A1, 1B1, 2B6,
      2E1, and 3A5) and human liver microsomes. The incubations were carried out in the
      presence or absence of the metabolite trapping agents glutathione, methoxylamine,
      and benzylamine. The metabolism mixtures were analyzed by LC-radiochromatography,
      LC-MS, and LC-MS/MS. DPTU was mainly metabolically activated to reactive
      sulfoxides resulting in desulfurated adducts in both enzymatic systems used.
      Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of
      DPTU. The sensitizing capacity of the substrate (DPTU) and three metabolites was
      tested in the murine local lymph node assay. Two out of three metabolites tested
      were strong skin sensitizers, whereas DPTU itself, as previously known, was
      negative using this mouse model. In conclusion, DPTU forms highly reactive
      metabolites upon bioactivation by enzymes present in the skin. These metabolites
      are able to induce skin sensitization and are probable causes for DPTU allergy.
      To increase the possibilities of diagnosing contact allergy to DPTU-containing
      items, we suggest that suitable metabolites of DPTU should be used for screening
      testing.

PMID- 21073183
TI  - Compound set enrichment: a novel approach to analysis of primary HTS data.
AB  - The main goal of high-throughput screening (HTS) is to identify active chemical
      series rather than just individual active compounds. In light of this goal, a new
      method (called compound set enrichment) to identify active chemical series from
      primary screening data is proposed. The method employs the scaffold tree compound
      classification in conjunction with the Kolmogorov-Smirnov statistic to assess the
      overall activity of a compound scaffold. The application of this method to seven
      PubChem data sets (containing between 9389 and 263679 molecules) is presented,
      and the ability of this method to identify compound classes with only weakly
      active compounds (potentially latent hits) is demonstrated. The analysis
      presented here shows how methods based on an activity cutoff can distort activity
      information, leading to the incorrect activity assignment of compound series.
      These results suggest that this method might have utility in the rational
      selection of active classes of compounds (and not just individual active
      compounds) for followup and validation.

PMID- 21073184
TI  - Antioxidant coating of micronsize droplets for prevention of lipid peroxidation
      in oil-in-water emulsion.
AB  - Fast lipid peroxidation in emulsified oils results in carcinogens formation and
      product rancidity. Prevention of oxidative degradation in oil-in-water emulsion
      has been achieved by encapsulating of each droplet of dispersed phase in
      antioxidant multilayer coating shell. The fabrication comprised placing a surface
      active ionic emulsifier at the oil/water interface followed by stepwise alternate
      adsorption a biocompatible polyelectrolyte and antioxidant layers. Uncoupled
      polyelectrolyte macromolecules and antioxidant were thoroughly removed from
      formulation, thus the protection was entirely attributed to the droplets' shell.
      The experiments were performed using linseed oil, the richest source of highly
      unstable omega-3 alpha linolenic essential fatty acid. Bovine serum albumin (BSA)
      was exploited as an anionic emulsifier. The biodegradable coating shell was
      formed of poly-l-arginine (PARG) and dextran sulfate (DS) applied as a polycation
      and a polyanion respectively. Tannic acid (TA) known as a natural antioxidant and
      possessing antimicrobial properties was used as a protective remedy. Oil
      microdroplets coated with TA-containing shell displayed physical-chemical and
      mechanical stability in aqueous phase and over freeze-drying process as
      determined by zeta-potential measurements, dynamic light scattering (DLS), and
      confocal laser scanning microscopy (CLSM). Oxidation of emulsified oil was
      monitored by formation of malondialdehyde (MDA) in the samples quantified by
      Thiobarbituric Acid Reactive Substances (TBARS) assay. Coating shell with an
      incorporated layer of TA effectively suppressed oxidation in water-dispersed oil
      droplets and affected iron-catalyzed oxidation over 15 days of incubation at 37 
      degrees C in 0.3 mM FeBr2 solution. Antioxidant activity of TA-containing shell
      assembled around each oil droplet was found to be higher than that of mixed
      tocopherols (MT) added to linseed oil in concentration of 10000 ppm.

PMID- 21073182
TI  - Correlation between desorption force measured by atomic force microscopy and
      adsorption free energy measured by surface plasmon resonance spectroscopy for
      peptide-surface interactions.
AB  - Surface plasmon resonance (SPR) spectroscopy is a useful technique for
      thermodynamically characterizing peptide-surface interactions; however, its
      usefulness is limited to the types of surfaces that can readily be formed as thin
      layers on the nanometer scale on metallic biosensor substrates. Atomic force
      microscopy (AFM), on the other hand, can be used with any microscopically flat
      surface, thus making it more versatile for studying peptide-surface interactions.
      AFM, however, has the drawback of data interpretation due to questions regarding
      peptide-to-probe-tip density. This problem could be overcome if results from a
      standardized AFM method could be correlated with SPR results for a similar set of
      peptide-surface interactions so that AFM studies using the standardized method
      could be extended to characterize peptide-surface interactions for surfaces that
      are not amenable for characterization by SPR. In this article, we present the
      development and application of an AFM method to measure adsorption forces for
      host-guest peptides sequence on surfaces consisting of alkanethiol self-assembled
      monolayers (SAMs) with different functionality. The results from these studies
      show that a linear correlation exists between these data and the adsorption free
      energy (DeltaG(o)(ads)) values associated with a similar set of peptide-surface
      systems available from SPR measurements. These methods will be extremely useful
      to characterize thermodynamically the adsorption behavior for peptides on a much
      broader range of surfaces than can be used with SPR to provide information
      related to understanding protein adsorption behavior to these surfaces and to
      provide an experimental database that can be used for the evaluation,
      modification, and validation of force field parameters that are needed to
      represent protein adsorption behavior accurately for molecular simulations.

PMID- 21073185
TI  - Aerostat sampling of PCDD/PCDF emissions from the Gulf oil spill in situ burns.
AB  - Emissions from the in situ burning of oil in the Gulf of Mexico after the
      catastrophic failure of the Deepwater Horizon drilling platform were sampled for
      polychlorinated dibenzodioxins and polychlorinated dibenzofurans (PCDD/PCDF). A
      battery-operated instrument package was lofted into the plumes of 27 surface oil
      fires over a period of four days via a tethered aerostat to determine and
      characterize emissions of PCDD/PCDF. A single composite sample resulted in an
      emission factor of 2.0 ng toxic equivalency (TEQ) per kg of carbon burned, or 1.7
      ng TEQ per kg of oil burned, determined by a carbon balance method. Carbon was
      measured as CO(2) plus particulate matter, the latter of which has an emission
      factor of 0.088 kg/kg carbon burned. The average plume concentration
      approximately 200-300 m from the fire and about 75-200 m above sea level was
      <0.0002 ng TEQ/m(3).

PMID- 21073186
TI  - Designing science in a crisis: the Deepwater Horizon oil spill.

PMID- 21073189
TI  - Electrochemical fabrication of metal/organic/metal junctions for molecular
      electronics and sensing applications.
AB  - A simple electrochemical approach was used for fabricating electrode/metal
      nanowire/(molecule or polymer)/electrode junctions for sensing or molecular
      electronics applications. The procedure for fabricating these molecule-based
      devices involves electropolymerization of phenol or chemisorption of alkanethiols
      on one set of electrodes (E1) and electrodeposition of Ag metal nano/microwires
      on a second electrode (E2) which is ~5 MUm away from E1. Under appropriate
      deposition conditions, Ag nanowires grow from E2 and cross over to E1, forming a
      E1/(molecule or polymer)/Ag nanowire (NW)/E2 junction. The junction resistance
      was controlled by (1) electrodepositing polyphenol of varied densities on E1 and
      (2) assembling alkanethiols of different chain lengths on E1. Ag NWs at high
      resistance E1/polyphenol/Ag NW/E2 junctions functionalized with Pd monolayer
      protected clusters (MPCs) responded fast and reversibly to H(2) concentrations as
      low as 0.11% in a nitrogen carrier gas by a resistance decrease, likely due to
      volume expansion of the Pd nanoparticles, demonstrating the use of these
      electrochemically fabricated junctions for gas sensing applications.

PMID- 21073188
TI  - Screening level assessment of risks due to dioxin emissions from burning oil from
      the BP Deepwater Horizon Gulf of Mexico spill.
AB  - Between April 28 and July 19 of 2010, the U.S. Coast Guard conducted in situ oil
      burns as one approach used for the management of oil spilled after the explosion
      and subsequent sinking of the BP Deepwater Horizon platform in the Gulf of
      Mexico. The purpose of this paper is to describe a screening level assessment of
      the exposures and risks posed by the dioxin emissions from these fires. Using
      upper estimates for the oil burn emission factor, modeled air and fish
      concentrations, and conservative exposure assumptions, the potential cancer risk
      was estimated for three scenarios: inhalation exposure to workers, inhalation
      exposure to residents on the mainland, and fish ingestion exposures to residents.
      U.S. EPA's AERMOD model was used to estimate air concentrations in the immediate
      vicinity of the oil burns and NOAA's HYSPLIT model was used to estimate more
      distant air concentrations and deposition rates. The lifetime incremental cancer
      risks were estimated as 6 * 10(-8) for inhalation by workers, 6 * 10(-12) for
      inhalation by onshore residents, and 6 * 10(-8) for fish consumption by
      residents. For all scenarios, the risk estimates represent upper bounds and
      actual risks would be expected to be less.

PMID- 21073190
TI  - Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated
      glucocorticoid receptor agonists.
AB  - A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid
      receptor modulators is reported. SAR exploration led to the identification of 4
      hydroxyphenyl propanamide derivatives displaying good agonist activity in GR
      mediated transrepression assays and reduced agonist activity in GR-mediated
      transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity
      comparable to prednisolone in the rat carrageenan-induced paw edema model, with
      markedly decreased side effects with regard to increases in blood glucose and
      expression of hepatic tyrosine aminotransferase. A hypothetical binding mode
      accounting for the induction of the functional activity by a 4-hydroxyl group is
      proposed. 

PMID- 21073192
TI  - Morphology and water barrier properties of nanobiocomposites of kappa/iota-hybrid
      carrageenan and cellulose nanowhiskers.
AB  - The current study presents the development and characterization of novel
      carrageenan nanobiocomposites showing enhanced water barrier due to incorporation
      of cellulose nanowhiskers (CNW). CNW, prepared by acid hydrolysis of highly
      purified alpha cellulose microfibers, were seen to have a length of around 25-50
      nm and a cross section of ca. 5 nm when dispersed in the matrix. The
      nanobiocomposites were prepared by incorporating 1, 3, and 5 wt % of the CNW into
      a carrageenan matrix using a solution casting method. Morphological data (TEM and
      optical microscopy) of the nanocomposites containing CNW were compared with the
      morphology of the corresponding biocomposites containing the original cellulose
      microfibers and the differences discussed. Thermal stability by TGA, water vapor
      permeability, and percent water uptake were also determined. The main conclusion
      arising from the analysis of the results is that the nanobiocomposites containing
      3 wt % of CNW exhibited the lowest reduction in water vapor permeability, that
      is, ca. 71%, and that this reduction was largely attributed to a filler-induced
      water solubility reduction. This fully biobased nanoreinforced carrageenan can
      open new opportunities for the application of this biopolymer in food-packaging
      and -coating applications.

PMID- 21073191
TI  - A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits
      potent antidepressant effect.
AB  - 7,8-Dihydroxyflavone is a recently identified small molecular tropomyosin
      receptor-kinase B (TrkB) agonist. Our preliminary structural-activity
      relationship (SAR) study showed that the 7,8-dihydroxy groups are essential for
      the agonistic effect. To improve the lead compound's agonistic activity, we have
      conducted an extensive SAR study and synthesized numerous derivatives. We have
      successfully identified 4'-dimethylamino-7,8-dihydroxyflavone that displays
      higher TrkB agonistic activity than that of the lead. This novel compound also
      exhibits a more robust and longer TrkB activation effect in animals.
      Consequently, this new compound reveals more potent antiapoptotic activity.
      Interestingly, chronic oral administration of 4'-dimethylamino-7,8
      dihydroxyflavone and its lead strongly promotes neurogenesis in dentate gyrus and
      demonstrates marked antidepressant effects. Hence, our data support that the
      synthetic 4'-dimethylamino-7,8-dihydroxyflavone and its lead both are orally
      bioavailable TrkB agonists and possess potent antidepressant effects. 

PMID- 21073193
TI  - Response of glucosinolate and flavonoid contents and composition of Brassica rapa
      ssp. chinensis (L.) Hanelt to silica formulations used as insecticides.
AB  - Silica-based substances have increased in popularity in recent years as
      alternative insecticides in horticultural crop protection. However, no research
      has been conducted into the influence of silica on plant biochemistry.
      Formulations (Fossil Shield 90.0s, AE R974, AL-06-109, Surround) were applied
      electrostatically on pak choi. Plants were harvested on two dates to measure
      immediate (first) and decelerated (second) influence, as well as recovery
      following the removal of silica formulations. The predominant individual
      glucosinolate (GS) in pak choi Black Behi was 1-methoxy-3-indolylmethyl GS. A
      significant increase in total glucosinolate contents in all treatments was
      measured from the first to second harvest. During the first harvest, no changes
      in glucosinolate levels in plants were found in any of the treatments. After a 48
      h recovery period, two substances showed decreased amounts for indole GS compared
      to the control. Flavonoids (kaempferol and isorhamnetin) decreased from the first
      to second harvest. Kaempferol in particular decreased in treated plants from the
      first to second harvest date. The shading of leaves by silica mainly caused the
      decrease in secondary metabolites in treated plants. Treatments with silica
      formulations as an alternative insecticide cause shifts in the composition and
      contents of bioactive secondary metabolites in Brassica rapa spp. chinensis
      plants and should, therefore, be used with care to control insects. 

PMID- 21073194
TI  - Iron and zinc concentrations in grain and flour of winter wheat as affected by
      foliar application.
AB  - Human deficiencies of iron (Fe) and zinc (Zn) are worldwide problems.
      Biofortification of wheat could reduce Fe and Zn deficiencies in societies that
      depend on wheat consumption. This study investigated the effects of foliar
      application of Fe with or without Zn on the concentrations of Fe and Zn in grain
      and especially in flour of three wheat cultivars. On average, grain Fe
      concentration was increased significantly from 29.5 mg kg(-1) in the control to
      37.8, 35.9, or 34.9 mg kg(-1) by application of FeSO4, ferric citrate plus ZnSO4,
      or ferric citrate, respectively. As expected, grain Zn concentration was
      increased from 29.0 mg kg(-1) in the control to 45.7 or 39.6 mg kg(-1) by
      application of ferric citrate plus ZnSO4 or a complex of micronutrients. Although
      the Fe and Zn concentrations in flour were inherently lower than in bran and
      shorts made by experimental mill, the concentrations in flour were simultaneously
      increased from 10.4 to 12.4 mg kg(-1) for Fe and from 11.8 to 17.4 mg kg(-1) for
      Zn by application of ferric citrate plus ZnSO4. Importantly, Fe was peripherally
      localized within grain fractions and strictly limited to transport to endosperm,
      making it more difficult to increase the quantity of Fe in flour products by
      foliar Fe application, but the situation with Zn is promising because Zn is more
      readily transported to the endosperm than Fe. The current study increases the
      understanding of agronomic biofortification. 

PMID- 21073195
TI  - Changes in the sorption of diverse volatiles by Saccharomyces cerevisiae lees
      during sparkling wine aging.
AB  - The volatile profile of sparkling wine is influenced by the retention and release
      of volatile compounds by lees during the aging process. Here we attempted to
      identify the volatiles that are most retained by lees in aging conditions and to
      study how their sorption varies during aging. We estimated the lees sorption
      capacity for several representative volatile compounds in sparkling wine samples
      at a range of time points during aging by assessing the volatiles sorbed on the
      lees surface and those present in the corresponding wines. The sorption of
      volatiles was proportional to their hydrophobicity, and their retention by the
      lees surface changed during aging. The sorption of less hydrophobic compounds
      decreased after the first 2 months of aging, while that of the most hydrophobic
      volatiles increased until 18 months, and decreased dramatically thereafter. These
      results indicate that the length of aging on lees determines the type and the
      amount of wine volatiles removed with lees in the disgorging step. While most
      polar aromas seem to be released from the lees surface at the earliest stages of
      aging, highly hydrophobic compounds and esters in general are progressively
      retained and subsequently desorbed into wine. Changes in the physicochemical
      properties of the lees cell surface were monitored during aging, but these could
      explain only the decrease in the sorption of less hydrophobic compounds. 

PMID- 21073196
TI  - Herbicide resistances in Amaranthus tuberculatus: a call for new options.
AB  - Amaranthus tuberculatus is a major weed of crop fields in the midwestern United
      States. Making this weed particularly problematic to manage is its demonstrated
      ability to evolve resistance to herbicides. Herbicides to which A. tuberculatus
      has evolved resistance are photosystem II inhibitors, acetolactate synthase
      inhibitors, protoporphyrinogen oxidase inhibitors, and glyphosate. Many
      populations of A. tuberculatus contain more than one of these resistances,
      severely limiting the options for effective herbicide control. A survey of
      multiple-herbicide resistance in A. tuberculatus revealed that all populations
      resistant to glyphosate contained resistance to acetolactate synthase inhibitors,
      and 40% contained resistance to protoporphyrinogen oxidase inhibitors. The
      occurrences of multiple-herbicide resistances in A. tuberculatus illustrate the
      need for continued herbicide discovery efforts and/or the development of new
      strategies for weed management.

PMID- 21073197
TI  - Scan-rate-dependent current rectification of cone-shaped silica nanopores in
      quartz nanopipettes.
AB  - Here we report the voltammetric behavior of cone-shaped silica nanopores in
      quartz nanopipettes in aqueous solutions as a function of the scan rate, v.
      Current rectification behavior for silica nanopores with diameters in the range 4
      25 nm was studied. The rectification behavior was found to be strongly dependent
      on the scan rate. At low scan rates (e.g., v < 1 V/s), the rectification ratio
      was found to be at its maximum and relatively independent of v. At high scan
      rates (e.g., v > 200 V/s), a nearly linear current-voltage response was obtained.
      In addition, the initial voltage was shown to play a critical role in the current
      voltage response of cone-shaped nanopores at high scan rates. We explain this v
      dependent current-voltage response by ionic redistribution in the vicinity of the
      nanopore mouth.

PMID- 21073198
TI  - Phosphorus chemical shifts in a nucleic acid backbone from combined molecular
      dynamics and density functional calculations.
AB  - A comprehensive quantum chemical analysis of the influence of backbone torsion
      angles on (31)P chemical shifts in DNAs has been carried out. An extensive DFT
      study employed snapshots obtained from the molecular dynamics simulation of
      [d(CGCGAATTCGCG)]2 to construct geometries of a hydrated dimethyl phosphate,
      which was used as a model for the phosphodiester linkage. Our calculations
      provided differences of 2.1 +/- 0.3 and 1.6 +/- 0.3 ppm between the B(I) and
      B(II) chemical shifts in two B-DNA residues of interest, which is in a very good
      agreement with the difference of 1.6 ppm inferred from experimental data. A more
      negative (31)P chemical shift for a residue in pure BI conformation compared to
      residues in mixed B(I)/B(II) conformation states is provided by DFT, in agreement
      with the NMR experiment. Statistical analysis of the MD/DFT data revealed a large
      dispersion of chemical shifts in both B(I) and B(II) regions of DNA structures.
      deltaP ranges within 3.5 +/- 0.8 ppm in the B(I) region and within 4.5 +/- 1.5
      ppm in the B(II) region. While the (31)P chemical shift becomes more negative
      with increasing alpha in B(I)-DNA, it has the opposite trend in B(II)-DNA when
      both alpha and zeta increase simultaneously. The (31)P chemical shift is
      dominated by the torsion angles alpha and zeta, while an implicit treatment of
      beta and epsilon is sufficient. The presence of an explicit solvent leads to a
      damping and a 2-3 ppm upfield shift of the torsion angle dependences.

PMID- 21073200
TI  - Stable and tunable phosphorescent neutral cyclometalated Au(III) diaryl
      complexes.
AB  - A series of novel luminescent cyclometalated Au(III) neutral complexes of the
      type cis-[(N(?)C)AuL] [N(?)C = 2-phenylpyridine (ppy), L = 1,1'-biphenyl (1)] and
      cis-[(N(?)C)AuL(2)] [N(?)C = 2-phenylpyridine (ppy), L = C(6)H(5) (2), C(6)F(5)
      (3), C(6)H(4)-CF(3)-p (4), 2-C(4)H(3)S (5)]; [N(?)C = 2-(2-thienyl)pyridine
      (thpy), L = C(6)H(5) (6), C(6)F(5) (7)]; [N(?)C = 2-(5-methyl-2-thienyl)pyridine
      (5 m-thpy), L = C(6)F(5) (8)] were successfully synthesized. The X-ray crystal
      structures of all compounds except 3 have been determined. These complexes were
      found to show long-lived emission in solution at room temperature. The emission
      origins of the complexes have been tentatively assigned to be derived from
      triplet states predominantly bearing intraligand (IL) character with some
      perturbation from the metal center. Density functional theory (DFT) calculations
      were performed to evaluate the stability associated with the complexes and TD-DFT
      calculations to ascertain the nature of the excited state. Variation of the
      cyclometalated ligands in the complexes readily leads to the tuning of the nature
      of the lower energy emissive states.

PMID- 21073199
TI  - New approaches toward recognition of nucleic acid triple helices.
AB  - A DNA duplex can be recognized sequence-specifically in the major groove by an
      oligodeoxynucleotide (ODN). The resulting structure is a DNA triple helix, or
      triplex. The scientific community has invested significant research capital in
      the study of DNA triplexes because of their robust potential for providing new
      applications, including molecular biology tools and therapeutic agents. The
      triplex structures have inherent instabilities, however, and the recognition of
      DNA triplexes by small molecules has been attempted as a means of strengthening
      the three-stranded complex. Over the decades, the majority of work in the field
      has focused on heterocycles that intercalate between the triplex bases. In this
      Account, we present an alternate approach to recognition and stabilization of DNA
      triplexes. We show that groove recognition of nucleic acid triple helices can be
      achieved with aminosugars. Among these aminosugars, neomycin is the most
      effective aminoglycoside (groove binder) for stabilizing a DNA triple helix. It
      stabilizes both the TAT triplex and mixed-base DNA triplexes better than known
      DNA minor groove binders (which usually destabilize the triplex) and polyamines.
      Neomycin selectively stabilizes the triplex (TAT and mixed base) without any
      effect on the DNA duplex. The selectivity of neomycin likely originates from its
      potential and shape complementarity to the triplex Watson-Hoogsteen groove,
      making it the first molecule that selectively recognizes a triplex groove over a
      duplex groove. The groove recognition of aminoglycosides is not limited to DNA
      triplexes, but also extends to RNA and hybrid triple helical structures.
      Intercalator-neomycin conjugates are shown to simultaneously probe the base
      stacking and groove surface in the DNA triplex. Calorimetric and spectrosocopic
      studies allow the quantification of the effect of surface area of the
      intercalating moiety on binding to the triplex. These studies outline a novel
      approach to the recognition of DNA triplexes that incorporates the use of
      noncompeting binding sites. These principles of dual recognition should be
      applicable to the design of ligands that can bind any given nucleic acid target
      with nanomolar affinities and with high selectivity.

PMID- 21073201
TI  - Dynamic origins of differential RNA binding function in two dsRBDs from the miRNA
      "microprocessor" complex.
AB  - MicroRNAs (miRNAs) affect gene regulation by base pairing with mRNA and
      contribute to the control of cellular homeostasis. The first step in miRNA
      maturation is conducted in the nucleus by the "microprocessor" complex made up of
      an RNase III enzyme, Drosha, that contains one dsRNA binding domain (dsRBD), and
      DGCR8, that contains two dsRBDs in tandem. The crystal structure of DGCR8-Core
      (493-720), containing both dsRBDs, and the NMR solution structure of Drosha-dsRBD
      (1259-1337) have been reported, but the solution dynamics have not been explored
      for any of these dsRBDs. To better define the mechanism of dsRNA binding and thus
      the nuclear maturation step of miRNA processing, we report NMR spin relaxation
      and MD simulations of Drosha-dsRBD (1259-1337) and DGCR8-dsRBD1 (505-583). The
      study was motivated by electrophoretic mobility shift assays (EMSAs) of the two
      dsRBDs, which showed that Drosha-dsRBD does not bind a representative miRNA but
      isolated DGCR8-dsRBD1 does (K(d) = 9.4 +/- 0.4 MUM). Our results show that loop 2
      in both dsRBDs is highly dynamic but the pattern of the correlations observed in
      MD is different for the two proteins. Additionally, the extended loop 1 of Drosha
      dsRBD is more flexible than the corresponding loop in DGCR8-dsRBD1 but shows no
      correlation with loop 2, which potentially explains the lack of dsRNA binding by
      Drosha-dsRBD in the absence of the RNase III domains. The results presented in
      this study provide key structural and dynamic features of dsRBDs that contribute
      to the binding mechanism of these domains to dsRNA.

PMID- 21073204
TI  - Glutathione complex formation with mercury(II) in aqueous solution at
      physiological pH.
AB  - The mercury(II) complexes formed in neutral aqueous solution with glutathione
      (GSH, here denoted AH(3) in its triprotonated form) were studied using Hg L(III)
      edge extended X-ray absorption fine structure (EXAFS) and (199)Hg NMR
      spectroscopy, complemented with electrospray ionization mass spectrometric (ESI
      MS) analyses. The [Hg(AH)(2)](2-) complex, with the Hg-S bond distances at 2.325
      +/- 0.01 A in linear S-Hg-S coordination, and the (199)Hg NMR chemical shift at 
      984 ppm, dominates except at high excess of glutathione. In a series of solutions
      with C(Hg(II)) ~17 mM and GSH/Hg(II) mole ratios rising from 2.4 to 11.8, the
      gradually increasing mean Hg-S bond distance corresponds to an increasing amount
      of the [Hg(AH)(3)](4-) complex. ESI-MS peaks appear at -m/z values of 1208 and
      1230 corresponding to the [Na(4)Hg(AH)(2)(A)](-) and [Na(5)Hg(AH)(A)(2)](-)
      species, respectively. In another series of solutions at pH 7.0 with C(Hg(II))
      ~50 mM and GSH/Hg(II) ratios from 2.0 to 10.0, the Hg L(III)-edge EXAFS and
      (199)Hg NMR spectra show that at high excess of glutathione (~0.35 M) about ~70%
      of the total mercury(II) concentration is present as the [Hg(AH)(3)](4-) complex,
      with the average Hg-S bond distance 2.42 +/- 0.02 A in trigonal HgS(3)
      coordination. The proportions of HgS(n) species, n = 2, 3, and 4, quantified by
      fitting linear combinations of model EXAFS oscillations to the experimental EXAFS
      data in our present and previous studies were used to obtain stability constants
      for the [Hg(AH)(3)](4-) complex and also for the [Hg(A)(4)](10-) complex that is
      present at high pH. For Hg(II) in low concentration at physiological conditions
      (pH 7.4, C(GSH) = 2.2 mM), the relative amounts of the HgS(2) species
      [Hg(AH)(2)](2-), [Hg(AH)(A)](3-), and the HgS(3) complex [Hg(AH)(3)](4-) were
      calculated to be 95:2:3. Our results are not consistent with the formation of
      dimeric Hg(II)-GSH complexes proposed in a recent EXAFS study.

PMID- 21073207
TI  - Efficient algorithm for asymptotics-based configuration-interaction methods and
      electronic structure of transition metal atoms.
AB  - Asymptotics-based configuration-interaction (CI) methods [G. Friesecke and B. D.
      Goddard, Multiscale Model. Simul. 7, 1876 (2009)] are a class of CI methods for
      atoms which reproduce, at fixed finite subspace dimension, the exact Schrodinger
      eigenstates in the limit of fixed electron number and large nuclear charge. Here
      we develop, implement, and apply to 3d transition metal atoms an efficient and
      accurate algorithm for asymptotics-based CI. Efficiency gains come from exact
      (symbolic) decomposition of the CI space into irreducible symmetry subspaces at
      essentially linear computational cost in the number of radial subshells with
      fixed angular momentum, use of reduced density matrices in order to avoid having
      to store wave functions, and use of Slater-type orbitals (STOs). The required
      Coulomb integrals for STOs are evaluated in closed form, with the help of Hankel
      matrices, Fourier analysis, and residue calculus. Applications to 3d transition
      metal atoms are in good agreement with experimental data. In particular, we
      reproduce the anomalous magnetic moment and orbital filling of chromium in the
      otherwise regular series Ca, Sc, Ti, V, Cr.

PMID- 21073206
TI  - Availability of and access to orphan drugs: an international comparison of
      pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease,
      hereditary angioedema and chronic myeloid leukaemia.
AB  - BACKGROUND: Market authorization does not guarantee patient access to any given
      drug. This is particularly true for costly orphan drugs because access depends
      primarily on co-payments, reimbursement policies and prices. The objective of
      this article is to identify differences in the availability of orphan drugs and
      in patient access to them in 11 pharmaceutical markets: Australia, Canada,
      England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland
      and the US. METHODS: Four rare diseases were selected for analysis: pulmonary
      arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and
      chronic myeloid leukaemia (CML). Indicators for availability were defined as (i)
      the indications for which orphan drugs had been authorized in the treatment of
      these diseases; (ii) the application date; and (iii) the date upon which these
      drugs received market authorization in each country. Indicators of patient access
      were defined as (i) the outcomes of technology appraisals; (ii) the extent of
      coverage provided by healthcare payers; and (iii) the price of the drugs in each
      country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil
      (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we
      analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant,
      ecallantide and two complement C1s inhibitors; for CML we analysed imatinib,
      dasatinib and nilotinib. RESULTS: Most drugs included in this study had received
      market authorization in all countries, but the range of indications for which
      they had been authorized differed by country. The broadest range of indications
      was found in Australia, and the largest variations in indications were found for
      PAH drugs. Authorization process speed (the time between application and market
      authorization) was fastest in the US, with an average of 362 days, followed by
      the EU (394 days). The highest prices for the included drugs were found in
      Germany and the US, and the lowest in Canada, Australia and England. Although the
      prices of all of the included drugs were high compared with those of most non
      orphan drugs, most of the insurance plans in our country sample provided coverage
      for authorized drugs after a certain threshold. CONCLUSIONS: Availability of and
      access to orphan drugs play a key role in determining whether patients will
      receive adequate and efficient treatment. Although the present study showed some
      variations between countries in selected indicators of availability and access to
      orphan drugs, virtually all of the drugs in question were available and
      accessible in our sample. However, substantial co-payments in the US and Canada
      represent important barriers to patient access, especially in the case of
      expensive treatments such as those analysed in this study. Market exclusivity is
      a strong instrument for fostering orphan drug development and drug availability.
      However, despite the positive effect of this instrument, the conditions under
      which market exclusivity is granted should be reconsidered in cases where the
      costs of developing an orphan drug have already been amortized through the use of
      the drug's active ingredient for the treatment of a common indication.

PMID- 21073208
TI  - Calibration study of the CCSD(T)-F12a/b methods for C2 and small hydrocarbons.
AB  - Explicitly correlated CCSD(T)-F12a/b methods combined with basis sets
      specifically designed for this technique have been tested for their ability to
      reproduce standard CCSD(T) benchmark data covering 16 small molecules composed of
      hydrogen and carbon. The standard method calibration set was obtained with very
      large one-particle basis sets, including some aug-cc-pV7Z and aug-cc-pV8Z
      results. Whenever possible, the molecular properties (atomization energies,
      structures, and harmonic frequencies) were extrapolated to the complete basis set
      limit in order to facilitate a direct comparison of the standard and explicitly
      correlated approaches without ambiguities arising from the use of different basis
      sets. With basis sets of triple-zeta quality or better, the F12a variant was
      found to overshoot the presumed basis set limit, while the F12b method converged
      rapidly and uniformly. Extrapolation of F12b energies to the basis set limit was
      found to be very effective at reproducing the best standard method atomization
      energies. Even extrapolations based on the small cc-pVDZ-F12/cc-pVTZ-F12
      combination proved capable of a mean absolute deviation of 0.20 kcal/mol. The
      accuracy and simultaneous cost savings of the F12b approach are such that it
      should enable high quality property calculations to be performed on chemical
      systems that are too large for standard CCSD(T).

PMID- 21073209
TI  - Application of second-order Moller-Plesset perturbation theory with resolution-of
      identity approximation to periodic systems.
AB  - Efficient periodic boundary condition (PBC) calculations by the second-order
      Moller-Plesset perturbation (MP2) method based on crystal orbital formalism are
      developed by introducing the resolution-of-identity (RI) approximation of four
      center two-electron repulsion integrals (ERIs). The formulation and
      implementation of the PBC RI-MP2 method are presented. In this method, the mixed
      auxiliary basis functions of the combination of Poisson and Gaussian type
      functions are used to circumvent the slow convergence of the lattice sum of the
      long-range ERIs. Test calculations of one-dimensional periodic trans
      polyacetylene show that the PBC RI-MP2 method greatly reduces the computational
      times as well as memory and disk sizes, without the loss of accuracy, compared to
      the conventional PBC MP2 method.

PMID- 21073210
TI  - Quantum theory of molecular collisions in a magnetic field: efficient
      calculations based on the total angular momentum representation.
AB  - An efficient method is presented for rigorous quantum calculations of atom
      molecule and molecule-molecule collisions in a magnetic field. The method is
      based on the expansion of the wave function of the collision complex in basis
      functions with well-defined total angular momentum in the body-fixed coordinate
      frame. We outline the general theory of the method for collisions of diatomic
      molecules in the (2)Sigma and (3)Sigma electronic states with structureless atoms
      and with unlike (2)Sigma and (3)Sigma molecules. The cross sections for elastic
      scattering and Zeeman relaxation in low-temperature collisions of
      CaH((2)Sigma(+)) and NH((3)Sigma(-)) molecules with (3)He atoms converge quickly
      with respect to the number of total angular momentum states included in the basis
      set, leading to a dramatic (>10-fold) enhancement in computational efficiency
      compared to the previously used methods [A. Volpi and J. L. Bohn, Phys. Rev. A
      65, 052712 (2002); R. V. Krems and A. Dalgarno, J. Chem. Phys. 120, 2296 (2004)].
      Our approach is thus well suited for theoretical studies of strongly anisotropic
      molecular collisions in the presence of external electromagnetic fields.

PMID- 21073211
TI  - Quantum wavepacket ab initio molecular dynamics: generalizations using an
      extended Lagrangian treatment of diabatic states coupled through multireference
      electronic structure.
AB  - We present a generalization to our previously developed quantum wavepacket ab
      initio molecular dynamics (QWAIMD) method by using multiple diabatic electronic
      reduced single particle density matrices, propagated within an extended
      Lagrangian paradigm. The Slater determinantal wavefunctions associated with the
      density matrices utilized may be orthogonal or nonorthogonal with respect to each
      other. This generalization directly results from an analysis of the variance in
      electronic structure with quantum nuclear degrees of freedom. The diabatic
      electronic states are treated here as classical parametric variables and
      propagated simultaneously along with the quantum wavepacket and classical nuclei.
      Each electronic density matrix is constrained to be N-representable. Consequently
      two sets of new methods are derived: extended Lagrangian-QWAIMD (xLag-QWAIMD) and
      diabatic extended Lagrangian-QWAIMD (DxLag-QWAIMD). In both cases, the
      instantaneous potential energy surface for the quantum nuclear degrees of freedom
      is constructed from the diabatic states using an on-the-fly nonorthogonal
      multireference formalism. By introducing generalized grid-based electronic basis
      functions, we eliminate the basis set dependence on the quantum nucleus.
      Subsequent reuse of the two-electron integrals during the on-the-fly potential
      energy surface computation stage yields a substantial reduction in computational
      costs. Specifically, both xLag-QWAIMD and DxLag-QWAIMD turn out to be about two
      orders of magnitude faster than our previously developed time-dependent
      deterministic sampling implementation of QWAIMD. Energy conservation properties,
      accuracy of the associated potential surfaces, and vibrational properties are
      analyzed for a family of hydrogen bonded systems.

PMID- 21073212
TI  - Multireference general-model-space state-universal and state-specific coupled
      cluster approaches to excited states.
AB  - The concept of C-conditions, originally introduced in the framework of the
      multireference (MR), general-model-space (GMS), state-universal (SU), coupled
      cluster (CC) approach with singles and doubles (GMS-SU-CCSD) to account for the
      internal amplitudes that vanish in the case of a complete model space, is applied
      to a state-selective or state-specific Mukherjee MR-CC method (MkCCSD). In
      contrast to the existing applications, the emphasis is on the description of
      excited states, particularly those belonging to the same symmetry species. The
      applicability of the C-conditions in all MR-SU-CC approaches is emphasized.
      Convergence problems encountered in the MkCCSD method when handling higher-lying
      states are pointed out. The performance of the GMS-SU-CCSD and MkCCSD methods is
      illustrated by considering low-lying vertical excitation energies of the ethylene
      molecule and para-benzyne diradical. A comparison with the equation-of-motion
      CCSD results, as well as with the available experimental data and recent
      multireference configuration interaction theoretical results, is also provided.

PMID- 21073213
TI  - Theoretical characterization of the SiC3H- anion.
AB  - Highly correlated ab initio methods are used to predict the equilibrium
      structures and spectroscopic parameters of the SiC(3)H(-) anion. The total
      energies and physical properties are reported using CASSCF/MRCI, RCCSD(T), and
      RCCSD(T)-F12 approaches and extended basis sets. The search of stable geometries
      leads to a total of 12 isomers (4 linear and 8 cyclic), for which electronic
      ground states have close-shell configurations. The stability of the linear form,
      l-SiC(3)H(-), is prominent. For the most stable linear isomer, the B(e)
      equilibrium rotational constant has been calculated with RCCSD(T) and a complete
      basis set. Core-correlation and vibrational effects have been taken into account
      to predict a B(0) of 2621.68 MHz for l-SiC(3)H(-) and 2460.48 MHz for l-SiC(3)D(
      ). The dipole moment of l-SiC(3)H(-) was found to be 2.9707 D with CASSCF/aug-cc
      pV5Z and the electron affinity to be 2.7 eV with RCCSD(T)-F12A/aug-cc-pVTZ.
      Anharmonic spectroscopic parameters are derived from a quadratic, cubic, and
      quartic RCCSD(T)-F12A force field and second order perturbation theory.
      CASSCF/MRCI vertical excitations supply three metastable electronic states,
      (1)Sigma(+) (3)Sigma(+) and (3)Delta. Electron affinities calculated for a series
      of chains type SiC(n)H and SiC(n) (n=1-5) allow us to discuss the anion formation
      probabilities.

PMID- 21073214
TI  - Iterative linearized density matrix propagation for modeling coherent excitation
      energy transfer in photosynthetic light harvesting.
AB  - Rather than incoherent hopping between chromophores, experimental evidence
      suggests that the excitation energy transfer in some biological light harvesting
      systems initially occurs coherently, and involves coherent superposition states
      in which excitation spreads over multiple chromophores separated by several
      nanometers. Treating such delocalized coherent superposition states in the
      presence of decoherence and dissipation arising from coupling to an environment
      is a significant challenge for conventional theoretical tools that either use a
      perturbative approach or make the Markovian approximation. In this paper, we
      extend the recently developed iterative linearized density matrix (ILDM)
      propagation scheme [E. R. Dunkel et al., J. Chem. Phys. 129, 114106 (2008)] to
      study coherent excitation energy transfer in a model of the Fenna-Matthews-Olsen
      light harvesting complex from green sulfur bacteria. This approach is
      nonperturbative and uses a discrete path integral description employing a short
      time approximation to the density matrix propagator that accounts for
      interference between forward and backward paths of the quantum excitonic system
      while linearizing the phase in the difference between the forward and backward
      paths of the environmental degrees of freedom resulting in a classical-like
      treatment of these variables. The approach avoids making the Markovian
      approximation and we demonstrate that it successfully describes the coherent
      beating of the site populations on different chromophores and gives good
      agreement with other methods that have been developed recently for going beyond
      the usual approximations, thus providing a new reliable theoretical tool to study
      coherent exciton transfer in light harvesting systems. We conclude with a
      discussion of decoherence in independent bilinearly coupled harmonic chromophore
      baths. The ILDM propagation approach in principle can be applied to more general
      descriptions of the environment.

PMID- 21073215
TI  - pCCSD: parameterized coupled-cluster theory with single and double excitations.
AB  - The primary characteristics of single reference coupled-cluster (CC) theory are
      size-extensivity and size-consistency, invariance under orbital rotations of the
      occupied or virtual space, the exactness of CC theory for N electron systems when
      the cluster operator is truncated to N-tuple excitations, and the relative
      insensitivity of CC theory to the choice of the reference determinant. In this
      work, we propose a continuous class of methods which display the desirable
      features of the coupled-cluster approach with single and double excitations
      (CCSD). These methods are closely related to the CCSD method itself and are
      inspired by the coupled electron pair approximation (CEPA). It is demonstrated
      that one can systematically improve upon CCSD and obtain geometries, harmonic
      vibrational frequencies, and total energies from a parameterized version of CCSD
      or pCCSD(alpha,beta) by selecting a specific member from this continuous family
      of approaches. In particular, one finds that one such approach, the pCCSD(-1,1)
      method, is a significant improvement over CCSD for the calculation of equilibrium
      structures and harmonic frequencies. Moreover, this method behaves surprisingly
      well in the calculation of potential energy surfaces for single bond
      dissociation. It appears that this methodology has significant promise for
      chemical applications and may be particularly useful in applications to larger
      molecules within the framework of a high accuracy local correlation approach.

PMID- 21073216
TI  - Constant pressure ab initio molecular dynamics with discrete variable
      representation basis sets.
AB  - The use of discrete variable representation (DVR) basis sets within ab initio
      molecular dynamics calculations allows the latter to be performed with converged
      energies and, more importantly, converged forces. In this paper, we show how to
      carry out ab initio molecular dynamics calculations in the isothermal-isobaric
      ensemble with fully flexible simulation boxes within the DVR basis set framework.
      In particular, we derive the appropriate DVR based expression for the pressure
      tensor when the electronic structure is represented using Kohn-Sham density
      functional theory, and we examine the convergence of this expression as a
      function of the basis set size. An illustrative example using 64 silicon atoms in
      a fully flexible box using a combination of the Martyna-Tobias-Klein [Martyna et
      al., J. Chem. Phys. 101, 4177 (1994)] and Car-Parrinello [Car and Parinello,
      Phys. Rev. Lett. 55, 2471 (1985)] algorithms is presented to demonstrate the
      efficacy of the approach.

PMID- 21073217
TI  - Toward spectroscopic accuracy for open-shell systems: molecular structure and
      hyperfine coupling constants of H2CN, H2CP, NH2, and PH2 as test cases.
AB  - In the present paper, we investigate the molecular structure and hyperfine
      couplings of a series of sigma radicals containing first- and second-row atoms
      (H(2)CN,H(2)CP,NH(2),PH(2)) for which accurate gas-phase microwave results are
      available. The presence of alpha- and, especially, beta-hydrogen atoms makes the
      evaluation of magnetic properties of these radicals particularly challenging.
      Geometrical parameters have been computed by the coupled-cluster ansatz in
      conjunction with hierarchical series of basis sets, thus accounting for
      extrapolation to the complete basis-set limit. Core correlation as well as higher
      excitations in the electronic-correlation treatment have also been taken into
      account. An analogous approach has been employed for evaluating hyperfine
      coupling constants with particular emphasis given to basis-set, correlation, and
      geometrical effects. The corresponding vibrational corrections, required for a
      meaningful comparison to experimental data, have also been investigated. The
      remarkable agreement with experiment confirms the reliability of the present
      computational approach, already validated for pi radicals, thus establishing the
      way for setting up a benchmark database for magnetic properties.

PMID- 21073218
TI  - Dipole moment surface of the van der Waals complex CH4-N2.
AB  - The interaction-induced dipole moment surface of the van der Waals CH(4)-N(2)
      complex has been calculated for a broad range of intermolecular separations R and
      configurations in the approximation of the rigid interacting molecules at the MP2
      and CCSD(T) levels of theory using the correlation-consistent aug-cc-pVTZ basis
      set with the basis set superposition error correction. The simple model to
      account for the exchange effects in the range of small overlap of the electron
      shells of interacting molecules and the induction and dispersion interactions for
      large R has been suggested. This model allows describing the dipole moment of van
      der Waals complexes in analytical form both for large R, where induction and
      dispersion have the key role, and for smaller R including whole ranges of their
      potential wells, where the exchange effects are important. The proposed model was
      tested on a number of configurations of the CH(4)-N(2) complex and was applied
      for the analytical description of the dipole moment surface for the family of the
      most stable configurations of the CH(4)-N(2) complex.

PMID- 21073219
TI  - Transient infrared spectra of CH3SOO and CH3SO observed with a step-scan Fourier
      transform spectrometer.
AB  - A step-scan Fourier-transform spectrometer coupled with a multipass absorption
      cell was employed to monitor time-resolved infrared absorption of transient
      species produced upon irradiation at 248 nm of a flowing mixture of CH(3)SSCH(3)
      and O(2) at 260 K. Two transient bands observed with origins at 1397+/-1 and
      1110+/-3 cm(-1) are tentatively assigned to the antisymmetric CH(3)-deformation
      and O-O stretching modes of syn-CH(3)SOO, respectively; the observed band contour
      indicates that the less stable anti-CH(3)SOO conformer likely contributes to
      these absorption bands. A band with an origin at 1071+/-1 cm(-1), observed at a
      slightly later period, is assigned to the S=O stretching mode of CH(3)SO, likely
      produced via secondary reactions of CH(3)SOO. These bands fit satisfactorily with
      vibrational wavenumbers and rotational contours simulated based on rotational
      parameters of syn-CH(3)SOO, anti-CH(3)SOO, and CH(3)SO predicted with density
      functional theories B3LYP/aug-cc-pVTZ and B3P86/aug-cc-pVTZ. Two additional bands
      near 1170 and 1120 cm(-1) observed at a later period are tentatively assigned to
      CH(3)S(O)OSCH(3) and CH(3)S(O)S(O)CH(3), respectively; both species are likely
      produced from self-reaction of CH(3)SOO. The production of SO(2) via secondary
      reactions was also observed and possible reaction mechanism is discussed.

PMID- 21073220
TI  - Hydrogen dissociation on small aluminum clusters.
AB  - Transition states and reaction paths for a hydrogen molecule dissociating on
      small aluminum clusters have been calculated using density functional theory. The
      two lowest spin states have been taken into account for all the Al(n) clusters
      considered, with n=2-6. The aluminum dimer, which shows a (3)Pi(u) electronic
      ground state, has also been studied at the coupled cluster and configuration
      interaction level for comparison and to check the accuracy of single determinant
      calculations in this special case, where two degenerate configurations should be
      taken into account. The calculated reaction barriers give an explanation of the
      experimentally observed reactivity of hydrogen on Al clusters of different size
      [Cox et al., J. Chem. Phys. 84, 4651 (1986)] and reproduce the high observed
      reactivity of the Al(6) cluster. The electronic structure of the Al(n)-H(2)
      systems was also systematically investigated in order to determine the role
      played by interactions of specific molecular orbitals for different nuclear
      arrangements. Singlet Al(n) clusters (with n even) exhibit the lowest barriers to
      H(2) dissociation because their highest doubly occupied molecular orbitals allow
      for a more favorable interaction with the antibonding sigma(u) molecular orbital
      of H(2).

PMID- 21073221
TI  - A ground state morphed intermolecular potential for the hydrogen bonded and van
      der Waals isomers in OC:HI and a prediction of an anomalous deuterium isotope
      effect.
AB  - An extended analysis of the noncovalent interaction OC:HI is reported using
      microwave and infrared supersonic jet spectroscopic techniques. All available
      spectroscopic data then provide the basis for generating an accurately determined
      vibrationally complete semiempirical intermolecular potential function using a
      four-dimensional potential coordinate morphing methodology. These results are
      consistent with the existence of four bound isomers: OC-HI, OC-IH, CO-HI, and CO
      IH. Analysis also leads to unequivocal characterization of the common isotopic
      ground state as having the OC-HI structure and with the first excited state
      having the OC-IH structure with an energy of 3.4683(80) cm(-1) above the ground
      state. The potential is consistent with the following barriers between the pairs
      of isomers: 382(4) cm(-1) (OC-IH/OC-HI), 294(5) cm(-1) (CO-IH/CO-HI), 324(3) cm(
      1) (OC-IH/CO-IH), and 301(2) cm(-1) (OC-HI/CO-HI) defined with respect to each
      lower minimum. The potential is also determined to have a linear OC-IH van der
      Waals global equilibrium minimum structure having R(e)=4.180(11) A,
      theta(1)=0.00(1) degrees , and theta(2)=0.00(1) degrees . This is differentiated
      from its OC-HI ground state hydrogen bound structure having R(0)=4.895(1) A,
      theta(1)=20.48(1) degrees , and theta(2)=155.213(1) degrees  where the distances
      are defined between the centers of mass of the monomers and theta(1) and theta(2)
      as cos(-1)[<cos(2) theta(i)>(1/2)] for i=1 and 2. A fundamentally new molecular
      phenomenon - ground state isotopic isomerization is proposed based on the
      generated semiempirical potential. The protonated ground state hydrogen-bonded OC
      HI structure is predicted to be converted on deuteration to the corresponding
      ground state van der Waals OC-ID isomeric structure. This results in a large
      anomalous isotope effect in which the R(0) center of mass distance between
      monomeric components changes from 4.895(1) to 4.286(1) A. Such a proposed
      isotopic effect is demonstrated to be a consequence of differential zero point
      energy factors resulting from the shallower nature of hydrogen bonding at a local
      potential minimum (greater quartic character of the potential) relative to the
      corresponding van der Waals global minimum. Further consequences of this
      anomalous deuterium isotope effect are also discussed.

PMID- 21073222
TI  - Singlet and triplet potential surfaces for the O2+C2H4 reaction.
AB  - Electronic structure calculations at the CASSCF and UB3LYP levels of theory with
      the aug-cc-pVDZ basis set were used to characterize structures, vibrational
      frequencies, and energies for stationary points on the ground state triplet and
      singlet O(2)+C(2)H(4) potential energy surfaces (PESs). Spin-orbit couplings
      between the PESs were calculated using state averaged CASSCF wave functions. More
      accurate energies were obtained for the CASSCF structures with the MRMP2/aug-cc
      pVDZ method. An important and necessary aspect of the calculations was the need
      to use different CASSCF active spaces for the different reaction paths on the
      investigated PESs. The CASSCF calculations focused on O(2)+C(2)H(4) addition to
      form the C(2)H(4)O(2) biradical on the triplet and singlet surfaces, and
      isomerization reaction paths ensuing from this biradical. The triplet and singlet
      C(2)H(4)O(2) biradicals are very similar in structure, primarily differing in
      their C-C-O-O dihedral angles. The MRMP2 values for the O(2)+C(2)H(4)
      >C(2)H(4)O(2) barrier to form the biradical are 33.8 and 6.1 kcal/mol,
      respectively, for the triplet and singlet surfaces. On the singlet surface,
      C(2)H(4)O(2) isomerizes to dioxetane and ethane-peroxide with MRMP2 barriers of
      7.8 and 21.3 kcal/mol. A more exhaustive search of reaction paths was made for
      the singlet surface using the UB3LYP/aug-cc-pVDZ theory. The triplet and singlet
      surfaces cross between the structures for the O(2)+C(2)H(4) addition transition
      states and the biradical intermediates. Trapping in the triplet biradical
      intermediate, following (3)O(2)+C(2)H(4) addition, is expected to enhance triplet
      >singlet intersystem crossing.

PMID- 21073223
TI  - A microwave study of hydrogen-transfer-triggered methyl-group rotation in 5
      methyltropolone.
AB  - We present here the first experimental and theoretical study of the microwave
      spectrum of 5-methyltropolone, which can be visualized as a seven-membered
      "aromatic" carbon ring with a five-membered hydrogen-bonded cyclic structure at
      the top and a methyl group at the bottom. The molecule is known from earlier
      studies in the literature to exhibit two large-amplitude motions, an
      intramolecular hydrogen transfer and a methyl torsion. The former motion is
      particularly interesting because transfer of the hydrogen atom from the hydroxyl
      to the carbonyl group induces a tautomerization in the molecule, which then
      triggers a 60 degrees  internal rotation of the methyl group. Measurements were
      carried out by Fourier-transform microwave spectroscopy in the 8-24 GHz frequency
      range. Theoretical analysis was carried out using a tunneling-rotational
      Hamiltonian based on a G(12)(m) extended-group-theory formalism. Our global fit
      of 1015 transitions to 20 molecular parameters gave a root-mean-square deviation
      of 1.5 kHz. The tunneling splitting of the two J=0 levels arising from a
      hypothetical pure hydrogen-transfer motion is calculated to be 1310 MHz. The
      tunneling splitting of the two J=0 levels arising from a hypothetical pure methyl
      top internal-rotation motion is calculated to be 885 MHz. We have also carried
      out ab initio calculations, which support the structural parameters determined
      from our spectroscopic analysis and give estimates of the barriers to the two
      large-amplitude motions.

PMID- 21073224
TI  - Growth of polyaromatic molecules via ion-molecule reactions: an experimental and
      theoretical mechanistic study.
AB  - The reactivity of naphthyl cations with benzene is investigated in a joint
      experimental and theoretical approach. Experiments are performed by using guided
      ion beam tandem mass spectrometers equipped with electron impact or atmospheric
      pressure chemical ion sources to generate C(10)H(7)(+) with different amounts of
      internal excitation. Under single collision conditions, C-C coupling reactions
      leading to hydrocarbon growth are observed. The most abundant ionic products are
      C(16)H(13)(+), C(16)H(n)(+) (with n=10-12), and C(15)H(10)(+). From pressure
      dependent measurements, absolute cross sections of 1.0+/-0.3 and 2+/-0.6 A(2) (at
      a collision energy of about 0.2 eV in the center of mass frame) are derived for
      channels leading to the formation of C(16)H(12)(+) and C(15)H(10)(+) ions,
      respectively. From cross section values a phenomenological total rate constant
      k=(5.8+/-1.9)*10(-11) cm(3) s(-1) at an average collision energy of about 0.27 eV
      can be estimated for the process C(10)H(7)(+)+C(6)H(6)->all products. The energy
      behavior of the reactive cross sections, as well as further experiments performed
      using partial isotopic labeling of reagents, support the idea that the reaction
      proceeds via a long lived association product, presumably the covalently bound
      protonated phenylnaphthalene, from which lighter species are generated by
      elimination of neutral fragments (H, H(2), CH(3)). A major signal relevant to the
      fragmentation of the initial adduct C(16)H(13)(+) belongs to C(15)H(10)(+). Since
      it is not obvious how CH(3) loss from C(16)H(13)(+) can take place to form the
      C(15)H(10)(+) radical cation, a theoretical investigation focuses on possible
      unimolecular transformations apt to produce it. Naphthylium can act as an
      electrophile and add to the pi system of benzene, leading to a barrierless
      formation of the ionic adduct with an exothermicity of about 53 kcal mol(-1).
      From this structure, an intramolecular electrophilic addition followed by H
      shifts and ring opening steps leads to an overall exothermic loss (-7.1 kcal mol(
      1) with respect to reagents) of the methyl radical from that part of the system
      which comes from benzene. Methyl loss can take place also from the "naphthyl"
      part, though via an endoergic route. Experimental and theoretical results show
      that an ionic route is viable for the growth of polycyclic aromatic species by
      association of smaller building blocks (naphthyl and phenyl rings) and this may
      be of particular relevance for understanding the formation of large molecules in
      ionized gases.

PMID- 21073225
TI  - Energy-transfer and charge-separation pathways in the reaction center of
      photosystem II revealed by coherent two-dimensional optical spectroscopy.
AB  - The excited state dynamics and relaxation of electrons and holes in the
      photosynthetic reaction center of photosystem II are simulated using a two-band
      tight-binding model. The dissipative exciton and charge carrier motions are
      calculated using a transport theory, which includes a strong coupling to a
      harmonic bath with experimentally determined spectral density, and reduces to the
      Redfield, the Forster, and the Marcus expressions in the proper parameter
      regimes. The simulated third order two-dimensional signals, generated in the
      directions -k(1)+k(2)+k(3), k(1)-k(2)+k(3), and k(1)+k(2)-k(3), clearly reveal
      the exciton migration and the charge-separation processes.

PMID- 21073226
TI  - Spherical polymer brushes under good solvent conditions: molecular dynamics
      results compared to density functional theory.
AB  - A coarse grained model for flexible polymers end-grafted to repulsive spherical
      nanoparticles is studied for various chain lengths and grafting densities under
      good solvent conditions by molecular dynamics methods and density functional
      theory. With increasing chain length, the monomer density profile exhibits a
      crossover to the star polymer limit. The distribution of polymer ends and the
      linear dimensions of individual polymer chains are obtained, while the
      inhomogeneous stretching of the chains is characterized by the local persistence
      lengths. The results on the structure factor of both single chain and full
      spherical brush as well as the range of applicability of the different
      theoretical tools are presented. Finally, a brief discussion of the experiment is
      given.

PMID- 21073227
TI  - Polymer escape from a metastable Kramers potential: path integral hyperdynamics
      study.
AB  - We study the dynamics of flexible, semiflexible, and self-avoiding polymer chains
      moving under a Kramers metastable potential. Due to thermal noise, the polymers,
      initially placed in the metastable well, can cross the potential barrier, but
      these events are extremely rare if the barrier is much larger than thermal
      energy. To speed up the slow rate processes in computer simulations, we extend
      the recently proposed path integral hyperdynamics method to the cases of
      polymers. We consider the cases where the polymers' radii of gyration are
      comparable to the distance between the well bottom and the barrier top. We find
      that, for a flexible polymers, the crossing rate (R) monotonically decreases with
      chain contour length (L), but with the magnitude much larger than the Kramers
      rate in the globular limit. For a semiflexible polymer, the crossing rate
      decreases with L but becomes nearly constant for large L. For a fixed L, the
      crossing rate becomes maximum at an intermediate bending stiffness. For the self
      avoiding chain, the rate is a nonmonotonic function of L, first decreasing with
      L, and then, above a certain length, increasing with L. These findings can be
      instrumental for efficient separation of biopolymers.

PMID- 21073228
TI  - Shape anisotropy of polymers in disordered environment.
AB  - We study the influence of structural obstacles in a disordered environment on the
      size and shape characteristics of long flexible polymer macromolecules. We use
      the model of self-avoiding random walks on diluted regular lattices at the
      percolation threshold in space dimensions d=2 and d=3. Applying the pruned
      enriched Rosenbluth method, we numerically estimate rotationally invariant
      universal quantities such as the averaged asphericity <A(d)> and prolateness <S>
      of polymer chain configurations. Our results quantitatively reveal the extent of
      anisotropy of macromolecules due to the presence of structural defects.

PMID- 21073229
TI  - Molecular dynamics simulations of supramolecular polymer rheology.
AB  - Using equilibrium and nonequilibrium molecular dynamics simulations, we studied
      the equilibrium and rheological properties of dilute and semidilute solutions of
      head-to-tail associating polymers. In our simulation model, a spontaneous
      complementary reversible association between the donor and the acceptor groups at
      the ends of oligomers was achieved by introducing a combination of truncated
      pseudo-Coulombic attractive potential and Lennard Jones repulsive potential
      between donor, acceptor, and neighboring groups. We have calculated the
      equilibrium properties of supramolecular polymers, such as the ring/chain
      equilibrium, average molecular weight, and molecular weight distribution of self
      assembled chains and rings, which all agree well with previous analytical and
      computer modeling results. We have investigated shear thinning of solutions of 8-
      and 20-bead associating oligomers with different association energies at
      different temperatures and oligomer volume fractions. All reduced viscosity data
      for a given oligomer length can be collapsed into one master curve, exhibiting
      two power-law regions of shear-thinning behavior with an exponent of -0.55 at
      intermediate ranges of the reduced shear rate beta and -0.8 (or -0.9) at larger
      shear rates. The equilibrium viscosity of supramolecular solutions with different
      oligomer lengths and associating energies is found to obey a power-law scaling
      dependence on oligomer volume fraction with an exponent of 1.5, in agreement with
      the experimental observations for several dilute or semidilute solutions of
      supramolecular polymers. This implies that dilute and semidilute supramolecular
      polymer solutions exhibit high polydispersity but may not be sufficiently
      entangled to follow the reptation mechanism of relaxation.

PMID- 21073230
TI  - Modifying infrared scattering effects of single yeast cells with plasmonic metal
      mesh.
AB  - The scattering effects in the infrared (IR) spectra of single, isolated bread
      yeast cells (Saccharomyces cerevisiae) on a ZnSe substrate and in metal
      microchannels have been probed by Fourier transform infrared imaging
      microspectroscopy. Absolute extinction [(3.4+/-0.6)*10(-7) cm(2) at 3178 cm(-1)],
      scattering, and absorption cross sections for a single yeast cell and a
      vibrational absorption spectrum have been determined by comparing it to the
      scattering properties of single, isolated, latex microspheres (polystyrene, 5.0
      MUm in diameter) on ZnSe, which are well modeled by the Mie scattering theory.
      Single yeast cells were then placed into the holes of the IR plasmonic mesh,
      i.e., metal films with arrays of subwavelength holes, yielding "scatter-free" IR
      absorption spectra, which have undistorted vibrational lineshapes and a rising
      generic IR absorption baseline. Absolute extinction, scattering, and absorption
      spectral profiles were determined for a single, ellipsoidal yeast cell to
      characterize the interplay of these effects.

PMID- 21073231
TI  - Detecting coupled collective motions in protein by independent subspace analysis.
AB  - Protein dynamics evolves in a high-dimensional space, comprising aharmonic,
      strongly correlated motional modes. Such correlation often plays an important
      role in analyzing protein function. In order to identify significantly correlated
      collective motions, here we employ independent subspace analysis based on the
      subspace joint approximate diagonalization of eigenmatrices algorithm for the
      analysis of molecular dynamics (MD) simulation trajectories. From the 100 ns MD
      simulation of T4 lysozyme, we extract several independent subspaces in each of
      which collective modes are significantly correlated, and identify the other modes
      as independent. This method successfully detects the modes along which long
      tailed non-Gaussian probability distributions are obtained. Based on the time
      cross-correlation analysis, we identified a series of events among domain motions
      and more localized motions in the protein, indicating the connection between the
      functionally relevant phenomena which have been independently revealed by
      experiments.

PMID- 21073232
TI  - The Third q-bio Conference on Cellular Information Processing.

PMID- 21073233
TI  - Shaping the response: the role of FcepsilonRI and Syk expression levels in mast
      cell signaling.
AB  - Many receptor systems initiate cell signaling through ligand-induced receptor
      aggregation. For bivalent ligands binding to mono- or bivalent receptors, a plot
      of the equilibrium concentration of receptors in aggregates against the log of
      the free ligand concentration, the cross-linking curve, is symmetric and bell
      shaped. However, steady state cellular responses initiated through receptor cross
      linking may have a different dependence on ligand concentration than the
      aggregated receptors that initiate and maintain these responses. The authors
      illustrate by considering the activation of the protein kinase Syk that rapidly
      occurs after high affinity receptors for IgE, FcepsilonRI, are aggregated on the
      surface of mast cells and basophils. Using a mathematical model of Syk activation
      the authors investigate two effects, one straightforward and one less so, that
      result in Syk activation not qualitatively following the cross-linking curve.
      Model predictions show that if the mechanism by which Syk is fully activated
      involves the transphosphorylation of Syk by Syk, then Syk activation curves can
      be either bell shaped or double humped, depending on the cellular concentrations
      of Syk and FcepsilonRI. The model also predicts that the Syk activation curve can
      be non-symmetric with respect to the ligand concentration. The cell can exhibit
      differential Syk activation at two different ligand concentrations that produce
      identical distributions of receptor aggregates that form and dissociate at the
      same rates. The authors discuss how, even though it is only receptor aggregates
      that trigger responses, differences in total ligand concentration can lead to
      subtle kinetic effects that yield qualitative differences in the levels of Syk
      activation.

PMID- 21073235
TI  - Identification from stochastic cell-to-cell variation: a genetic switch case
      study.
AB  - Owing to the inherently random and discrete nature of genes, RNAs and proteins
      within living cells, there can be a wide range of variability both over time in a
      single cell and from cell to cell in a population of genetically identical cells.
      Different mechanisms and reaction rates help shape this variability in different
      ways, and the resulting cell-to-cell variability can be quantitatively measured
      using techniques such as time-lapse microscopy and fluorescence activated cell
      sorting (or flow cytometry). It has been shown that these measurements can help
      to constrain the parameters and mechanisms of stochastic gene regulatory models.
      In this work, finite state projection approaches are used to explore the
      possibility of identifying the parameters of a specific stochastic model for the
      genetic toggle switch consisting of mutually inhibiting proteins: LacI and cI.
      This article explores the possibility of identifying the model parameters from
      different types of statistical information, such as mean expression levels, LacI
      protein distributions and LacI-cI multivariate distributions. It is determined
      that although the toggle model parameters cannot be uniquely identified from
      measurements that track just the LacI variability, the parameters could be
      identified from measurements of the cell-to-cell variability in both regulatory
      proteins. Based upon the simulated data and the computational investigations of
      this study, experiments are proposed that could enable this identification.

PMID- 21073234
TI  - Spatial gradients in kinase cascade regulation.
AB  - The spatiotemporal kinetics of proteins and other substrates regulate cell fate
      and signaling. In this study, we consider a reaction-diffusion model of
      interaction of membrane receptors with a two-step kinase cascade. The receptors
      activate the 'up-stream' kinase, which may diffuse over cell volume and activate
      the 'down-stream' kinase, which is also diffusing. Both kinase species and
      receptors are inactivated by uniformly distributed phosphatases. The positive
      feedback, key to the considered dynamics, arises since the up-stream kinase
      activates the receptors. Such a mutual interaction is characteristic for immune
      cell receptors. Based on the proposed model, we demonstrated that cell
      sensitivity (measured as a critical value of phosphatase activity at which cell
      maybe activated) increases with decreasing motility of receptor-interacting
      kinases and with increasing polarity of receptors distribution. These two effects
      are cooperating, the effect of receptors localisation close to one pole of the
      cell grows with the decreasing kinase diffusion and vanishes in the infinite
      diffusion limit. As the cell sensitivity increases with decreasing diffusion of
      receptor-interacting kinase, the overall activity of the down-stream kinase
      increases with its diffusion. In conclusion, the analysis of the proposed model
      shows that, for the fixed substrate interaction rates, spatial distribution of
      the surface receptors together with the motility of intracellular kinases control
      cell signalling and sensitivity to extracellular signals. The increase of the
      cell sensitivity can be achieved by (i) localisation of receptors in a small
      subdomain of the cell membrane, (ii) lowering the motility of receptor
      interacting kinase, (iii) increasing the motility of down-stream kinases which
      distribute the signal over the whole cell.

PMID- 21073236
TI  - Cell-penetrating peptides, electroporation and drug delivery.
AB  - Certain short polycations, such as trans-activating transcriptional activator and
      oligoarginine, rapidly pass through the plasma membranes of mammalian cells by a
      mechanism called transduction, as well as by endocytosis and macropinocytosis.
      These cell-penetrating peptides can carry with them cargos of 30 amino acids,
      more than the nominal limit of 500 Da and enough to be therapeutic. An analysis
      of the electrostatics of a charge outside the cell membrane and some recent
      experiments suggest that transduction may proceed by molecular electroporation.
      Ways to target diseased cells, rather than all cells, are discussed.

PMID- 21073238
TI  - Thermodynamic models of combinatorial gene regulation by distant enhancers.
AB  - The dynamical properties of distal and proximal gene regulatory elements are
      crucial to their functionality in gene regulatory networks. However, the
      multiplicity of regulatory interactions at control elements makes their
      theoretical and experimental characterisation difficult. Here a thermodynamic
      framework to describe gene regulation by distant enhancers via a chromatin
      mechanism is developed. In this mechanism transcription factors (TFs) modulate
      gene expression via shifts in the equilibrium between chromatin states. The
      designs of AND, OR, XOR and NAND two-input transcriptional gates for the
      chromatin mechanism are proposed and compared to similar gates based on the
      direct physical interactions of TFs with the transcriptional machinery. An
      algorithm is developed to estimate the thermodynamic parameters of chromatin
      mechanism gates from gene expression reporter data and applied to characterise
      the response function for the Gata2-3 enhancer in hematopoietic stem cells. In
      addition waiting-time distributions for transcriptionally active states were
      analysed to expose the biophysical differences between the contact and chromatin
      mechanisms. These differences can be experimentally observed in single-cell
      experiments and therefore can serve as a signature of the gene regulation
      mechanism. Taken together these results indicate the diverse functionality and
      unique features of the chromatin mechanism of combinatorial gene regulation.

PMID- 21073237
TI  - Defining cooperativity in gene regulation locally through intrinsic noise.
AB  - Regulatory networks in cells may comprise a variety of types of molecular
      interactions. The most basic are pairwise interactions, in which one species
      controls the behaviour of another (e.g. a transcription factor activates or
      represses a gene). Higher-order interactions, while more subtle, may be important
      for determining the function of networks. Here, the authors systematically expand
      a simple master equation model for a gene to derive an approach for robustly
      assessing the cooperativity (effective copy number) with which a transcription
      factor acts. The essential idea is that moments of a joint distribution of
      protein copy numbers determine the Hill coefficient of a cis-regulatory input
      function without non-linear fitting. The authors show that this method prescribes
      a definition of cooperativity that is meaningful even in highly complex
      situations in which the regulation does not conform to a simple Hill function. To
      illustrate the utility of the method, the authors measure the cooperativity of
      the transcription factor CI in simulations of phage- and show how the
      cooperativity accurately reflects the behaviour of the system. The authors
      numerically assess the effects of deviations from ideality, as well as possible
      sources of error. The relationship to other definitions of cooperativity and
      issues for experimentally realising the procedure are discussed.

PMID- 21073239
TI  - Time-dependent corrections to effective rate and event statistics in Michaelis
      Menten kinetics.
AB  - The authors generalise the concept of the geometric phase in stochastic kinetics
      to a non-cyclic evolution. Its application is demonstrated on kinetics of the
      Michaelis-Menten reaction. It is shown that the non-periodic geometric phase is
      responsible for the correction to the Michaelis-Menten law when parameters, such
      as a substrate concentration, are changing with time. The authors apply these
      ideas to a model of chemical reactions in a bacterial culture of a growing size,
      where the geometric correction qualitatively changes the outcome of the reaction
      kinetics.

PMID- 21073241
TI  - Multivariate dependence and genetic networks inference.
AB  - A critical task in systems biology is the identification of genes that interact
      to control cellular processes by transcriptional activation of a set of target
      genes. Many methods have been developed that use statistical correlations in high
      throughput data sets to infer such interactions. However, cellular pathways are
      highly cooperative, often requiring the joint effect of many molecules. Few
      methods have been proposed to explicitly identify such higher-order interactions,
      partially due to the fact that the notion of multivariate statistical dependence
      itself remains imprecisely defined. The authors define the concept of dependence
      among multiple variables using maximum entropy techniques and introduce
      computational tests for their identification. Synthetic network results reveal
      that this procedure uncovers dependencies even in undersampled regimes, when the
      joint probability distribution cannot be reliably estimated. Analysis of
      microarray data from human B cells reveals that third-order statistics, but not
      second-order ones, uncover relationships between genes that interact in a pathway
      to cooperatively regulate a common set of targets.

PMID- 21073240
TI  - Towards monitoring real-time cellular response using an integrated microfluidics
      matrix assisted laser desorption ionisation/nanoelectrospray ionisation-ion
      mobility-mass spectrometry platform.
AB  - The combination of microfluidic cell trapping devices with ion mobility-mass
      spectrometry offers the potential for elucidating in real time the dynamic
      responses of small populations of cells to paracrine signals, changes in
      metabolite levels and delivery of drugs and toxins. Preliminary experiments
      examining peptides in methanol and recording the interactions of yeast and Jurkat
      cells with their superfusate have identified instrumental set-up and control
      parameters and online desalting procedures. Numerous initial experiments
      demonstrate and validate this new instrumental platform. Future outlooks and
      potential applications are addressed, specifically how this instrumentation may
      be used for fully automated systems biology studies of the significantly
      interdependent, dynamic internal workings of cellular metabolic and signalling
      pathways.

PMID- 21073242
TI  - Fast adaptive uniformisation of the chemical master equation.
AB  - Within systems biology there is an increasing interest in the stochastic
      behaviour of biochemical reaction networks. An appropriate stochastic description
      is provided by the chemical master equation, which represents a continuous-time
      Markov chain (CTMC). The uniformisation technique is an efficient method to
      compute probability distributions of a CTMC if the number of states is
      manageable. However, the size of a CTMC that represents a biochemical reaction
      network is usually far beyond what is feasible. In this study, the authors
      present an on-the-fly variant of uniformisation, where they improve the original
      algorithm at the cost of a small approximation error. By means of several
      examples, the authors show that their approach is particularly well-suited for
      biochemical reaction networks.

PMID- 21073244
TI  - Veterinary History Museum in Zagreb - on the occasion of a jubilee monograph on
      the collection of veterinary instruments of the Zagreb University Faculty of
      Medicine.
AB  - To mark its 90th anniversary, the Faculty of Veterinary Medicine, University of
      Zagreb, published a book Collection of Veterinary Instruments from the Museum of
      Veterinary History, which is a significant contribution to the history of
      veterinary medicine of Croatia. The presented collection is on display in the
      Museum of Veterinary History at the Faculty of Veterinary Medicine. The Museum,
      an integral part of the Department of History of Veterinary Medicine, was founded
      by decree in 1936. It houses several collections: archives, veterinary and
      related literature, a collection of veterinary instruments, and a collection of
      horseshoes. The monograph presents the veterinary instruments which were of
      utmost importance for the development of veterinary science and practice.

PMID- 21073243
TI  - Rule-based modelling and simulation of biochemical systems with molecular finite
      automata.
AB  - The authors propose a theoretical formalism, molecular finite automata (MFA), to
      describe individual proteins as rule-based computing machines. The MFA formalism
      provides a framework for modelling individual protein behaviours and systems
      level dynamics via construction of programmable and executable machines. Models
      specified within this formalism explicitly represent the context-sensitive
      dynamics of individual proteins driven by external inputs and represent protein
      protein interactions as synchronised machine reconfigurations. Both deterministic
      and stochastic simulations can be applied to quantitatively compute the dynamics
      of MFA models. They apply the MFA formalism to model and simulate a simple
      example of a signal-transduction system that involves an MAP kinase cascade and a
      scaffold protein.

PMID- 21073245
TI  - [Meleda disease (Mal de Meleda): historical shifts in perception].
AB  - Nowadays, hereditary diseases are viewed through molecular mechanisms, and one of
      them, which keeps occurring rather frequently in medical publications, has been
      named after the Island of Mljet. The world first learned about mal de Meleda from
      a Dubrovnik physician Luka Stulli in 1826. He described it in a number of his
      island patients as a non-contagious hereditary skin disease, and named it mal de
      Meleda (a disease of Mljet). After Stulli, numerous scientists continued to
      investigate its aetiology and distinctive properties, introducing new scientific
      procedures to research the disease. The article keeps track of the way people and
      medicine perceived and treated mal de Meleda patients, starting from the early
      19th century to the present day. It pays special attention to how the disease was
      perceived and described in medical literature through history. There are no
      reports in writing about the disease before the 19th century, but in oral
      tradition it was perceived as a punishment for the sins of sacrilege, sins of
      piracy, or even as leftovers of leprosy brought by the crusaders. We investigated
      if these legends have any support in preserved historical documents and to what
      extent they are related to real historical events and circumstances. Influenced
      by the booming research in microbiology, end 19th century physicians believed the
      disease was an isolated focus of leprosy. However, early 20th century physicians
      defined it as a hereditary skin disease with changes which distinguish it from
      other skin conditions. Genetic nature of the disease was later confirmed by
      molecular science. As for its geographical origin, the most recent medical
      research has shown that mal de Meleda is not restricted to the island of Mljet,
      and that it is spread worldwide, particularly in regions that, historically, were
      the trading routes of the Dubrovnik Republic. This implies that the mutation has
      spread through migration and persists only because it is not lethal and does not
      affect reproduction.

PMID- 21073246
TI  - [Francesco Matiassi's 1908 design of the main city hospital of Rijeka].
AB  - In 1908, the City of Rijeka embarked on what would have been the biggest project
      ever. It planned to build a new city hospital that was to relieve the burden from
      the Saint Spirit Hospital, which could no longer meet local healthcare needs. The
      hospital was designed by one of Rijeka's finest architects, Francesco Matiassi
      and was to have 600 beds and cover an area of 40,000 sq m. In his design,
      Mattiassi implemented the programme and suggestions of the hospital head, Dr
      Antonio Grossich and the City technical department, headed by Luigi Luppis. The
      hospital complex was to be a combination of two types of buildings, common in
      hospital architecture of the time: the main building with a very complex floor
      plan, and four separate pavilions: mental illnesses, quarantine, post mortem, and
      services. The first three floors of the main building were intended for the
      departments of general medicine, surgery, gynaecology, maternity, infectious
      diseases, ophthalmology, and dermatology, and the remaining floors for patient
      reception, hospital supplies and utilities, administration, and staff. Glass
      walled operating theatres, terraces for patients and facilities such as a large
      cloakroom bear witness to the designer's deep understanding of civil culture and
      architecture, which set high standards even in today's terms. Even though the
      project was too ambitious and even utopian for a city like Rijeka at the
      beginning of the 20th century, we cannot but regret that it has not seen the
      light of day at least in part.

PMID- 21073247
TI  - [Natural scientists and medical bibliography in the Dominican Monastery of
      Dubrovnik].
AB  - This article speaks about Dubrovnik's Dominicans who were engaged in natural
      studies or wrote medical dissertations. It brings a list of manuscripts and
      printed works kept in the Dominican monastery library. These include six
      incunabulae and more than 200 works on anthropology, anatomy, hygiene, pharmacy,
      and general, theoretical, and practical medicine, internal and cerebral medicine,
      orthopaedics, surgery, ophthalmology, psychology, and gerontology. Tractates on
      all kinds of diseases, especially contagious, and their treatment, are also
      included. A portion of these works comes from donations by various doctors who
      worked in Dubrovnik, and others were acquired for the needs of the monastery
      pharmacy. These works were written in Latin, Italian, French, German, and
      Croatian. Such a wide range of works on almost all aspects of medicine is more
      akin to a professional library of a medical college than to a monastery library,
      howevergrand or important it really is.

PMID- 21073248
TI  - Johannes Ludwig Janson, professor of veterinary medicine in Tokyo in 1880-1902 -
      contribution to German-Japanese medical relations, part IV.
AB  - Among the German pioneers of Western medicine in Japan (8, 12) during the Meiji
      period (1868-1912), veterinary officer Johannes Ludwig Janson (1849-1914) was one
      of the most important figures. He arrived in Tokyo in October 1880 and taught at
      the Veterinary School in Komaba. During his tenure, the school in Komaba was
      integrated into the School of Agriculture of the Imperial University of Tokyo.
      Numerous of his graduates occupied high public offices. Among his publications,
      those about domestic animals and veterinary medicine in Japan deserve special
      attention. He married a Japanese girl and continued teaching in Komaba until
      1902. He found his last resting place in Kagoshima, the native place of his wife.
      To this day, the Japanese consider Janson the founder of modern veterinary
      medicine in their country.

PMID- 21073250
TI  - Participation of women in the 1992-1995 war in Bosnia and Herzegovina.
AB  - Many authors have written about the participation of women in WW2 in Bosnia and
      Herzegovina, mostly in health care. Participation of Bosnian and Herzegovinian
      women in the 1992-1995 war was also significant. According to Army of Bosnia and
      Herzegovina data, there were 5360 recruited women. Some were engaged in logistics
      and some were fighters. This review presents the characters of the brave women
      who have inspired current generations.

PMID- 21073249
TI  - [War health care system in Karlovac area during war in Croatia 1991-1995].
AB  - Croatian military medicine developed with the Croatian State and Army. Severe war
      conditions called for a military medicine that would integrate civil and military
      components: General Hospital Karlovac, medical corps of the Croatian Army, and
      emergency, preventive, and general medicine care. The wounded from the entire
      battlefield of the Karlovac area were admitted to and treated at the General
      Hospital Karlovac, totalling 1475 wounded, 39 of whom died of wounds. 229 people
      killed in action were directly admitted to the Department of Pathology. Medical
      Corps of the Croatian Army provided only primary health care services and
      emergency care. Due to the vicinity of the battlefield the classic echelon
      structure could not be followed in the Karlovac area. The third component was
      civilian emergency, preventive, and general medical care. Concept of
      collaboration between civilian and military medical services was successfully
      implemented in the Karlovac area, resulting in effective health care.

PMID- 21073251
TI  - The cause of P.I. Tchaikovsky's (1840-1893) death: cholera, suicide, or both?
AB  - The death of P. I. Tchaikovsky (1840 - 1893) excites imagination even today.
      According to the "official scenario", Tchaikovsky had suffered from abdominal
      colic before being infected with cholera. On 2 November 1893, he drank a glass of
      unboiled water. A few hours later, he had diarrhoea and started vomiting. The
      following day anuria occured. He lost consciousness and died on 6 November (or on
      25 Oktober according to the Russian Julian calendar). Soon after composer's
      death, rumors of forced suicide began to circulate. Based on the opinion of the
      musicologist Alexandra Orlova, the main reason for the composer's tragic fate
      lies in his homosexual inclination. The author of this article, after examining
      various sources and arguments, concludes that P. I. Tchaikovsky died of cholera.

PMID- 21073252
TI  - Ulcers of the face and neck in a woman with pulmonary tuberculosis: presentation
      of a clinical case.
AB  - INTRODUCTION: Tuberculosis (TB), which is endemic in developing countries, is an
      important public health problem. Cutaneous TB (CT) represents 1.5% of all TB
      cases and is considered to be a re-emerging pathology in developing countries due
      to co-infections with HIV, multidrug-resistant TB, a shortage of health
      facilities with appropriate diagnostic equipment, reduced access to treatment,
      and poor treatment compliance among patients who often resort to traditional
      medicine. CASE REPORT: This report describes the case of a 70 year-old woman who
      attended the outpatients department of the Italian Dermatological Centre (IDC) in
      Mekelle, the capital city of Tigray (Northern Ethiopia), complaining of the
      appearance of two ulcers on her face and neck. The patient had a history of
      pulmonary TB, with her initial systemic treatment ceased after 1 month.
      Cytological examination of a needle aspiration from the neck lesion showed a non
      specific bacterial superinfection. No acid-fast bacilli were found on Ziehl
      Nielsen staining. On the basis of clinical suspicion of CT, it was decided to
      avoid biopsy for histology and culture and to immediately start anti-tubercular
      treatment. A significant improvement of the cutaneous lesions was noted after
      approximately 40 days. CONCLUSION: Currently, the diagnosis of CT is based on
      careful clinical and histopathological correlation. The standard diagnostic
      approach is to biopsy for Ziehl-Nielsen stain, culture and histology. However, in
      rural areas of DC where diagnostic methods may not be available and advanced
      stages of disease such as CT are likely to be encountered, after the use of the
      most effective diagnostic tests available, empirical treatment on the basis of
      medical history and physical examination is suggested. Appropriate training of
      healthcare workers and public health education programs encouraging early
      presentation and improved patient treatment compliance are additional important
      preventative strategies.

PMID- 21073255
TI  - Balamuthia mandrillaris brain abscess successfully treated with complete surgical
      excision and prolonged combination antimicrobial therapy.
AB  - Amoebic encephalitis is an uncommon and usually fatal condition. This case
      describes successful treatment of a Balamuthia mandrillaris brain abscess using
      prolonged antimicrobial agents with complete excision. It illustrates the risk of
      dissemination from cutaneous to cerebral amoebic lesions, potential progression
      with corticosteroid therapy, and the prospect for curative excision.

PMID- 21073254
TI  - Effects of posttraumatic carbamylated erythropoietin therapy on reducing lesion
      volume and hippocampal cell loss, enhancing angiogenesis and neurogenesis, and
      improving functional outcome in rats following traumatic brain injury.
AB  - OBJECT: Carbamylated erythropoietin (CEPO) is a modified erythropoietin molecule
      that does not affect hematocrit. In this study, the authors compared the efficacy
      of a single dose with a triple dose of CEPO treatment for traumatic brain injury
      (TBI) in rats. METHODS: Traumatic brain injury was induced by controlled cortical
      impact over the left parietal cortex. Carbamylated erythropoietin (50 MUg/kg) was
      administered intraperitoneally in rats with TBI at 6 hours (CEPO * 1) or at 6,
      24, and 48 hours (CEPO * 3) postinjury. Neurological function was assessed using
      a modified neurological severity score and foot fault and Morris water maze
      tests. Animals were killed 35 days after injury, and brain sections were stained
      for immunohistochemical analysis to assess lesion volume, cell loss, cell
      proliferation, angiogenesis, and neurogenesis after CEPO treatment. RESULTS:
      Compared with the vehicle treatment, single treatment of CEPO (6 hours)
      significantly reduced lesion volume and hippocampal cell loss, enhanced
      angiogenesis and neurogenesis in the injured cortex and hippocampus, and
      significantly improved sensorimotor functional recovery and spatial learning in
      rats after TBI. Importantly, triple dosing of CEPO (6, 24, and 48 hours) further
      reduced lesion volume and improved functional recovery and neurogenesis compared
      with the CEPO * 1 group. CONCLUSIONS: The authors' results indicate that CEPO has
      considerable therapeutic potential in TBI and related pathologies and furthermore
      that repeated dosing in the subacute phase might have important pharmacological
      relevance.

PMID- 21073256
TI  - Glutamate clearance mechanisms in resected cortical dysplasia.
AB  - OBJECT: Changes in the expression of glutamate transporters (GLTs) may play a
      role in the expression of epileptogenicity. Previous studies have shown an
      increased number of neuronal GLTs in human dysplastic neurons. The expression of
      glial and neuronal GLTs and glutamine synthetase (GS) in balloon cells (BCs) and
      BC-containing cortical dysplasia has not been studied. METHODS: The authors
      analyzed neocortical samples that were resected in 5 patients who had cortical
      dysplasia-induced medically intractable focal epilepsy and who underwent
      extraoperative prolonged electrocorticographic (ECoG) recordings. The expressions
      of glial (GLT1/EAAT2) and neuronal (EAAT3, EAAC1) GLTs and GS proteins were
      immunohistochemically studied in all 5 resected samples. The authors also
      assessed in situ colocalization of GLTs and GS with neuronal and glial markers.
      RESULTS: Balloon cell-containing cortical dysplasia lesions did not exhibit ictal
      patterns on prolonged extraoperative ECoG recordings. There was a differential
      expression of glial and neuronal GLTs in BCs and dysplastic neurons: the majority
      of BCs highly expressed glial but not neuronal GLTs. Dysplastic neurons showed
      increased immunohistochemical staining with neuronal EAAT3 but not with
      EAAT2/GLT1. Moreover, only glial fibrillary acidic protein-positive BCs also
      expressed GS. CONCLUSIONS: There is a differential GLT expression in dysplastic
      and balloon cells. The presence of glial GLTs and GS in balloon cell cortical
      dysplasia suggests a possible antiepileptic role for BCs and is consistent with
      the reported increased epileptogenicity in GLT1-deficient animals.

PMID- 21073257
TI  - Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect
      and duration after intracisternal injection of magnesium sulfate solution in a
      canine subarachnoid hemorrhage model.
AB  - OBJECT: The optimal CSF Mg(++) concentration for vasodilation of spastic cerebral
      arteries after subarachnoid hemorrhage (SAH) and its duration are unknown. The
      temporal profile of the vasodilatory effect and optimal CSF Mg(++) concentration
      after the intracisternal injection of MgSO(4) solution were investigated in an
      SAH model in canines. METHODS: Cerebral vasospasm was induced by experimental SAH
      using a 2-hemorrhage model in 26 female beagles. On Day 7, 0.5 ml/kg of 15, 10,
      5, or 0 mmol/L MgSO(4) in Ringer solution was injected into the
      cerebellomedullary cistern. Angiography was performed on Day 1 (before SAH) and
      before and 1, 3, and 6 hours after the intracisternal injection on Day 7 to
      measure arterial diameters of the basilar artery (BA), superior cerebellar artery
      (SCA), and vertebral artery (VA). Cerebrospinal fluid Mg(++) was also measured at
      the same time. RESULTS: Arterial diameters of the BA, SCA, and VA were
      significantly decreased by vasospasm on Day 7. Arterial diameter ratios (ratio of
      arterial diameter after MgSO(4) injection to diameter before injection on Day 7)
      of the BA and SCA at 1 and 3 hours after and the VA at 1 hour after
      intracisternal injection of the MgSO(4) solution were positively correlated with
      the CSF Mg(++) concentration. All arterial diameter ratios, except 1 point of the
      SCA, exceeded 1 if the CSF Mg(++) concentration was > 3 mEq/L at 1 hour after
      injection. Animals with CSF Mg(++) concentrations > 3 mEq/L at 1 hour after
      injection (11 dogs) showed significantly increased arterial diameters of the BA
      at 1 and 3 hours after and of the SCA and VA at 1, 3, and 6 hours after
      injection, as compared with the diameters before injection. The CSF Mg(++)
      concentration significantly increased at 1 hour (3.73 +/- 0.69 mEq/L, p < 0.01)
      and 3 hours (2.05 +/- 0.35 mEq/L, p < 0.01) after the intracisternal injection as
      compared with the baseline value (1.41 +/- 0.20 mEq/L). CONCLUSIONS: The
      reversible effect of an intracisternal injection of MgSO(4) solution on the
      spastic artery requires CSF Mg(++) concentrations > 3 mEq/L. The vasodilatory
      effect continues for 3-6 hours after injection. These results suggest that the
      continuous infusion or intermittent intracisternal injection of MgSO(4) is needed
      to maintain the optimal CSF Mg(++) concentration and constantly ameliorate
      cerebral vasospasm.

PMID- 21073259
TI  - Priorities in developing the young adult classical singer at music college.

PMID- 21073258
TI  - Extraction and analysis of polyphenols: recent trends.
AB  - In recent years, there has been an increasing interest in diets rich in fruits
      and vegetables and this is mostly due to their presumed role in the prevention of
      various degenerative diseases, such as cancer and cardiovascular diseases. This
      is mainly due to the presence of bioactive compounds, such as polyphenols,
      carotenoids, among others. Polyphenols are one of the main classes of secondary
      metabolites derived from plants offering several health benefits resulting in
      their use as functional foods. Prior to the use of these polyphenols in specific
      applications, such as food, pharmaceutical, and the cosmetic industries, they
      need to be extracted from the natural matrices, then analyzed and characterized.
      The development of an efficient procedure for the extraction, proper analysis,
      and characterization of phenolic compounds from different sources is a
      challenging task due to the structural diversity of phenolic compounds, a complex
      matrix, and their interaction with other cellular components. In this light, this
      review discusses different methods of extraction, analysis, and the structural
      characterization of polyphenolic compounds.

PMID- 21073260
TI  - On combining information from modulation spectra and mel-frequency cepstral
      coefficients for automatic detection of pathological voices.
AB  - This work presents a novel approach for the automatic detection of pathological
      voices based on fusing the information extracted by means of mel-frequency
      cepstral coefficients (MFCC) and features derived from the modulation spectra
      (MS). The system proposed uses a two-stepped classification scheme. First, the
      MFCC and MS features were used to feed two different and independent classifiers;
      and then the outputs of each classifier were used in a second classification
      stage. In order to establish the best configuration which provides the highest
      accuracy in the detection, the fusion of information was carried out employing
      different classifier combination strategies. The experiments were carried out
      using two different databases: the one developed by The Massachusetts Eye and Ear
      Infirmary Voice Laboratory, and a database recorded by the Universidad
      Politecnica de Madrid. The results show that the combination of MFCC and MS
      features employing the proposed approach yields an improvement in the detection
      accuracy, demonstrating that both methods of parameterization are complementary.

PMID- 21073261
TI  - Cell therapy medical tourism: time for action.

PMID- 21073262
TI  - Ex-vivo expansion of NK cells: what is the priority--high yield or high purity?

PMID- 21073263
TI  - Cadmium as a transcriptional modulator in human cells.
AB  - Cadmium (Cd) is an underground mineral widely used in the steel industry, in
      plastics, and as a component of batteries. It is an industrial and environmental
      pollutant released as an air contaminant from fertilizers and, more prominently,
      in the form of wastewater. Food, drinking water, and, mainly, inhalation of smoke
      from cigarettes are sources of daily exposure of humans to the heavy metal.
      Although Cd has no known useful function for humans as well as other organisms,
      it appears to evoke in cells a number of responses that involve not only death
      signaling but also protective reactions against the toxicity. This finding
      prompted a number of experimental studies aimed to elucidate the cellular and
      molecular aspects of Cd-dependent regulation of gene expression and signal
      transduction pathways in different model system. Here, the authors briefly review
      the role of Cd as a transcriptional regulator in diverse cytotypes of human
      origin, focusing in particular on its effects on two classes of genes, i.e.,
      stress-response genes such as metallothioneins (MTs), heme oxygenase, and heat
      shock proteins (hsps), and apoptosis-related genes, but giving also an overview
      of many other examples of genes involved in cell metabolism and both
      intracellular and extracellular signalization whose expression levels are
      controlled by Cd.

PMID- 21073264
TI  - Correction to: M. tuberculosis Central Asian Strain 1 MDR isolates have more
      mutations in rpoB and katG genes compared with other genotypes.

PMID- 21073265
TI  - An active film-coating approach to enhance chemical stability of a potent drug
      molecule.
AB  - Peliglitazar, a PPAR alpha/gamma agonist, was found to undergo acid as well as
      base catalyzed degradation. The acid catalyzed degradation led to the formation
      of benzylic alcohol and glycine carbamate and the base catalyzed degradation led
      to formation of p-hydroxyanisole and an amine degradant. In capsule formulations,
      the capsules with the lowest drug-loading exhibited maximum instability even at
      25  degrees C/60% RH storage condition. Incorporation of pH-modifiers to maintain
      'micro-environmental pH' acidic did not prevent the formation of the base
      catalyzed degradants. Traditional dry granulated tablet formulation which is
      qualitatively similar to the capsule formulations showed the presence of acid
      catalyzed degradants even without the presence of an acidifying agent. On the
      other hand, traditional wet granulated tablet formulation showed mainly base
      catalyzed degradants. Stability problems of the tablet formulation were
      aggravated because the potent molecule required low tablet strengths which
      resulted in low drug to excipient ratio. To stabilize the molecule, an active
      film-coating approach was explored. In this approach, the drug was sprayed with
      the coating material onto non-active containing tablet cores. This approach of
      trapping the drug particles into the coating material provided tablets with
      satisfactory chemical stability. The stability enhancement observed in the active
      coating approach is attributed to the higher drug to excipient ratio in the film
      coat of non-reactive coating material compared to that in the traditional dry or
      wet granulated formulations.

PMID- 21073266
TI  - Commentary on Series: The research agenda for general practice/family medicine
      and primary health care in Europe. Part 5: Needs and implications for future
      research and policy.

PMID- 21073267
TI  - The impact of a nurse-led care programme on events and physical and psychosocial
      parameters in patients with heart failure with preserved ejection fraction: a
      randomized clinical trial in primary care in Russia.
AB  - BACKGROUND: Disease management programmes (DMPs) improve quality of care for
      patients with heart failure (HF). However, only a limited number of trials have
      studied the efficacy of such programmes for patients with heart failure with
      preserved ejection fraction (HFPEF). OBJECTIVE: To estimate the impact of a
      structured, nurse-led patient education programme and care plan in general
      practice on outcome parameters and events in patients with HFPEF. METHODS: Single
      blinded randomized clinical trial with an intervention over six months and a
      follow-up during 12 additional months. In the control group, the patients (n =
      41) were managed according to Russian national guidelines. Patients in the
      intervention group (n = 44) received education on individual lifestyle changes
      and modifications of cardiovascular disease (CVD) risk factors, home-based
      exercise training and weekly nurse consultations in addition to usual care.
      RESULTS: Six months after their inclusion, patients in the intervention group
      significantly improved body mass index, waist circumference, six-min walk test
      distance, total cholesterol, low-density lipoprotein, left ventricular end
      diastolic volume index, quality of life and level of anxiety. After 18 months,
      there were 11 deaths (25%) or hospitalizations in the intervention group and 12
      (29%) in the control group (P = 0.134). Cardiovascular mortality and readmission
      rate were not reduced significantly after six months of follow-up: the hazard
      ratio was 0.47 (95% CI: 0.17-1.28; P = 0.197). After 18 months, this was 0.85
      (0.42-1.73; P = 0.658). CONCLUSION: This primary care based DMP for patients with
      HFPEF improved the patients' emotional status and quality of life, positively
      influenced body weight, functional capacity and lipid profile, and attenuated
      heart remodelling.

PMID- 21073268
TI  - Series: The research agenda for general practice/family medicine and primary
      health care in Europe. Part 5: Needs and implications for future research and
      policy.
AB  - The recently published 'Research Agenda for General Practice/Family Medicine and
      Primary Health Care in Europe' summarizes the evidence relating to the core
      competencies and characteristics of the Wonca Europe definition of GP/FM, and
      highlights related needs and implications for future research and policy. The
      European Journal of General Practice publishes a series of articles based on this
      document. In a first article, background, objectives, and methodology were
      discussed. In three subsequent, articles the results for the six core
      competencies of the European Definition of GP/FM were presented. This article
      formulates the common aims for further research and appropriate research
      methodologies, based on the missing evidence and research gaps identified form
      the comprehensive literature review. In addition, implications of this research
      agenda for general practitioners/family doctors, researchers, research
      organizations, patients and policy makers are presented. The concept of six core
      competencies should be abandoned in favour of a model with four dimensions,
      including clinical, person related, community oriented and management aspects.
      Future research and policy should consider more the involvement and rights of
      patients; more attention should be given to how new treatments or technologies
      are effectively translated into routine patient care, in particular primary care.
      There is a need for a European ethics board. The promotion of GP/FM research
      demands a good infrastructure in each country, including access to literature and
      databases, appropriate funding and training possibilities.

PMID- 21073275
TI  - A novel ALS SOD1 C6S mutation with implications for aggregation related toxicity
      and genetic counseling.
AB  - In this report we describe an ALS family with a novel missense SOD1 mutation with
      substitution of serine for cysteine at the sixth amino acid (C6S). This mutation
      has interesting implications for the role of disulfides in causing disease. After
      identification of the ALS proband, we examined 17 members of an extended family
      and performed DNA mutation analysis on 21 family members. The level and activity
      of SOD1 in C6S carriers and wild-type family members was analyzed in
      erythrocytes. We found that the C6S mutation results in disease with an autosomal
      dominant mode of inheritance and markedly reduced penetrance. The S6 mutated
      protein demonstrates high stability relative to the C6 wild-type protein. The
      specific dismutation activity of S6 SOD1 is normal. In conclusion, C6S is a novel
      FALS associated mutation with reduced disease penetrance, long survival time and
      a phenotype very different from the other SOD1 mutations reported in codon C6.
      This mutation may provide insight into the role of SOD1 structural changes in
      disease.

PMID- 21073276
TI  - Identification of compounds protective against G93A-SOD1 toxicity for the
      treatment of amyotrophic lateral sclerosis.
AB  - The underlying cause of amyotrophic lateral sclerosis (ALS), a progressive
      neurodegenerative disorder, remains unknown. However, there is strong evidence
      that one pathophysiological mechanism, toxic protein misfolding and/or
      aggregation, may trigger motor neuron dysfunction and loss. Since the clinical
      and pathological features of sporadic and familial ALS are indistinguishable, all
      forms of the disease may be better understood and ultimately treated by studying
      pathogenesis and therapy in models expressing mutant forms of SOD1. We developed
      a cellular model in which cell death depended on the expression of G93A-SOD1, a
      mutant form of superoxide dismutase found in familial ALS patients that produces
      toxic protein aggregates. This cellular model was optimized for high throughput
      screening to identify protective compounds from a >50,000 member chemical
      library. Three novel chemical scaffolds were selected for further study following
      screen implementation, counter-screening and secondary testing, including studies
      with purchased analogs. All three scaffolds blocked SOD1 aggregation in high
      content screening assays and data on the optimization and further
      characterization of these compounds will be reported separately. These data
      suggest that optimization of these chemicals scaffolds may produce therapeutic
      candidates for ALS patients.

PMID- 21073277
TI  - Immune monitoring of pancreatic islet graft: towards a better understanding,
      detection and treatment of harmful events.
AB  - IMPORTANCE OF THE FIELD: Long-term clinical outcomes of islet transplantation are
      hampered by rejection and recurrence of autoimmunity, which lead to a gradual
      decrease in islet function usually taking place over the first five years after
      transplantation. An accurate monitoring strategy could allow for the detection
      and treatment of harmful immune events, potentially resulting in higher rates of
      insulin-independence. AREAS COVERED IN THIS REVIEW: This article provides a
      critical review of the various assays currently available for the assessment of
      allo- and autoimmunity both prior to and after islet transplantation. The
      accuracy in predicting clinical outcome is specifically addressed. WHAT THE
      READER WILL GAIN: Most current tests based on the assessment of allo- and auto
      immune antibody are of minimal help in clinical practice. Cell-based tests
      (including the assessment of cytotoxic T lymphocyte precursors, proliferation
      tests, enzyme-linked immunospot) have the potential to allow earlier and more
      accurate detection of harmful events. TAKE HOME MESSAGE: A specific and accurate
      immune monitoring has the potential to significantly improve islet transplant
      outcomes. The development and use of such tests (favouring cell-based tests)
      should be promoted.

PMID- 21073278
TI  - Blood substitutes in 2010 [ 1 ].

PMID- 21073280
TI  - IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases.
AB  - IL-19, IL-20 and IL-24 are members of the IL-10 family of cytokines, the human IL
      19, IL-20 and IL-24 genes are all located on the q32 region of chromosome 1, and
      the three cytokines also share a common receptor IL-20R1/IL-20R2 heterodimer.
      These cytokines due to the similarity and shared receptor usage, are quite
      overlapping in function. Recently, the available evidence has indicated that
      interaction of these cytokines with their receptors might exhibit pro
      inflammatory effects on autoimmune diseases, particularly psoriasis and
      rheumatoid arthritis. Since an imbalance between anti- and pro-inflammatory
      cytokines contribute to the development of autoimune diseases, these cytokines
      may be implicated in the pathogenesis of autoimmunity. In this paper, we
      concisely discuss the biological features of IL-19, IL-20 and IL-24, and focus on
      their potential roles in autoimmune diseases. Hopefully the information obtained
      will lead to a better understanding of the pathogenesis and development of novel
      therapeutic strategies for autoimmune diseases.

PMID- 21073282
TI  - The role of mining in the spread of TB in Africa: policy implications.

PMID- 21073281
TI  - Murine coronavirus neuropathogenesis: determinants of virulence.
AB  - Murine coronavirus, mouse hepatitis virus (MHV), causes various diseases
      depending on the strain and route of inoculation. Both the JHM and A59 strains,
      when inoculated intracranially or intranasally, are neurovirulent. Comparison of
      the highly virulent JHM isolate, JHM.SD, with less virulent JHM isolates and with
      A59 has been used to determine the mechanisms and genes responsible for high
      neuropathogenicity of MHV. The focus of this review is on the contributions of
      viral spread, replication, and innate and adaptive immunity to MHV
      neuropathogenesis. JHM.SD spreads more quickly among neurons than less
      neurovirulent MHVs, and is able to spread in the absence of the canonical MHV
      receptor, CEACAM1a. The observation that JHM.SD infects more cells and expresses
      more antigen, but produces less infectious virus per cell than A59, implies that
      efficient replication is not always a correlate of high neurovirulence. This is
      likely due to the unstable nature of the JHM.SD spike protein (S). JHM.SD induces
      a generally protective innate immune response; however, the strong neutrophil
      response may be more pathogenic than protective. In addition, JHM.SD induces only
      a minimal T-cell response, whereas the strong T-cell response and the concomitant
      interferon-gamma (IFN-gamma) induced by the less neurovirulent A59 is protective.
      Differences in the S and nucleocapsid (N) proteins between A59 and JHM.SD
      contribute to JHM.SD neuropathogenicity. The hemmagglutinin-esterase (HE) protein
      may enhance neuropathogenicity of some MHV isolates, but is unlikely a major
      contributor to the high neuroviruence of JHM.SD. Further data suggest that
      neither the internal (I) protein nor nonstructural proteins ns4, and ns2 are
      significant contributors to neurovirulence.

PMID- 21073283
TI  - Persistent cognitive impairment after cerebral malaria: models, mechanisms and
      adjunctive therapies.

PMID- 21073285
TI  - Nosocomial infections: new therapeutic alternatives.
AB  - This symposium on nosocomial infections, antimicrobial resistance and the
      benefits of doripenem in this setting was held in Madrid, Spain, on 7 October
      2009, and was supported by Janssen-Cilag. The topic was presented under an
      interdisciplinary approach by different international experts in the field.

PMID- 21073286
TI  - Pharmacoepidemiologic study of acute exacerbations of COPD: challenges and
      opportunities.
AB  - Guideline recommendations for the treatment of acute exacerbations of chronic
      obstructive pulmonary disease are derived from randomized clinical trials; they
      usually have a small sample size and are unrepresentative of patient populations.
      By contrast, observation data represent real-world patient population with large
      sample sizes and greater generalizability; however, appropriate methodologies are
      needed to analyze the data and make sound inference. This article reviews the
      study by Rothberg et al., summarizes the key findings, and extends the discussion
      to the challenges and opportunities of pharmacoepidemiologic studies in acute
      exacerbations of chronic obstructive pulmonary disease.

PMID- 21073287
TI  - Anaerobic environment of the intestine primes pathogenic Shigella for infection.
AB  - Marteyn et al. have investigated the role of oxygen and the regulator FNR in
      infection by the intracellular enteric pathogen Shigella flexneri. FNR is active
      under anaerobic conditions like those present in the lumen of the distal
      intestine. FNR causes elongation of a secretion apparatus required for bacterial
      entry into cells and represses secretion of proteins that trigger entry. Higher
      oxygen levels present at the intestinal cell surface are sufficient to inactivate
      FNR, thereby derepressing secretion. Thus, bacteria are 'primed' in the anaerobic
      environment of the lumen, and entry is triggered by the aerobic conditions at the
      intestinal cell surface. FNR is conserved among many enteric pathogens,
      suggesting that regulation of virulence in response to oxygen may be widely
      conserved.

PMID- 21073288
TI  - Identifying severe bacterial infection in children with fever without source.
AB  - For decades, many investigators have attempted to identify clinical or laboratory
      markers that can accurately differentiate severe bacterial from self-limiting
      viral infections in young children with fever without source. Unfortunately, no
      perfect marker has been discovered so far. Many guidelines recommend white blood
      cell count as a screening marker in fever without source, whereas compelling
      evidence in the literature emphasizes the superior characteristics of C-reactive
      protein and procalcitonin. One way to improve predictive value is the combination
      of prediction rules of different tests for clinical and laboratory markers.
      Several clinical decision rules, reviewed in this article, have been suggested
      but seem to be difficult to implement in practice due to their complexity.
      Recently, procalcitonin, C-reactive protein and urinary dipstick were combined in
      a simple risk index score that displayed promising predictive value in severe
      bacterial infections in children. Ultimately, impact analyses still have to be
      performed to show improved quality of care in this setting.

PMID- 21073289
TI  - Preventing catheter-related infections in children undergoing hemodialysis.
AB  - The increased use of tunneled cuffed catheters in children on chronic
      hemodialysis is the result of their relative ease of insertion, pain-free
      dialysis and immediate use. The disadvantage of their use is that they are
      associated with catheter-related bacteremia (CRB), which in turn is related with
      increased morbidity, access loss and occasionally metastatic infections and even
      death. A CRB might be difficult to diagnose and is often associated with a
      previous history of CRB, exit-site infection, low serum albumin and long duration
      of catheter use. There is evidence that the use of arteriovenous fistulae is
      associated with lower infection rates. The implementation of effective strategies
      for the prevention of CRBs include the adoption of policies for improving
      arteriovenous fistula rates, appropriate surgical catheter insertion and optimal
      nursing care of the exit site, and a safe connection technique. Recently, the
      effectiveness of antimicrobial catheter solutions for preventing CRB has been
      documented in a number of randomized clinical trials. In addition, the
      application of antibiotic ointments at the exit sites of tunneled cuffed
      catheters might be significant for the reduction of Staphylococcus-related CRB.
      The upside is that education-based programs combining specific preventive
      measures can significantly reduce CRBs.

PMID- 21073290
TI  - Minor extended-spectrum beta-lactamases.
AB  - Over the last few decades, various extended-spectrum beta-lactamases (ESBLs),
      which are remotely related to the classical TEM and SHV families, have emerged.
      Among these, CTX-M, VEB and PER variants are of particular interest due to their
      widespread dissemination. This article will focus on these emerging ESBLs. CTX-M
      was first identified from an Escherichia coli strain in Germany and since then, a
      rapidly growing family of ESBLs has formed worldwide. There are now more than 90
      CTX-M variants. VEB-1 ESBL is widespread in Southeast Asia. It was first
      identified in an E. coli strain isolated from a Vietnamese boy in 1996. After the
      initial discovery, it spread to other species. PER-1, now reported from various
      continents, was restricted to Turkish hospitals for years after the first
      identification in a strain of Pseudomonas aeruginosa in 1993. The worldwide
      dissemination of ESBLs is a healthcare crisis that deserves special attention.

PMID- 21073291
TI  - Fluoroquinolones in the management of community-acquired pneumonia in primary
      care.
AB  - A literature search was conducted to evaluate the pharmacokinetic and
      pharmacodynamic profile of the respiratory fluoroquinolones (gemifloxacin,
      levofloxacin and moxifloxacin) and their efficacy and safety in the management of
      community-acquired pneumonia (CAP). Data show that CAP is a common presentation
      in primary care practice, and is associated with high rates of morbidity and
      mortality, particularly in the elderly. Although the causative pathogens differ
      depending on treatment setting and patient factors, Streptococcus pneumoniae is
      the primary pathogen in all treatment settings. As a class, the respiratory
      fluoroquinolones have a very favorable pharmacokinetic and pharmacodynamic
      profile. Pharmacodynamic criteria suggest that moxifloxacin and gemifloxacin are
      more potent against S. pneumoniae, which may have the added benefit of reducing
      resistance selection and enhancing bacterial eradication. The respiratory
      fluoroquinolones are also generally well tolerated, and are first-line options
      for outpatient treatment of CAP in patients with comorbidities or previous
      antibiotic use.

PMID- 21073292
TI  - Nucleic acid amplification-based diagnosis of respiratory virus infections.
AB  - The appearance of eight new respiratory viruses in the human population in the
      past 9 years, including two new pandemics (SARS coronavirus in 2003 and swine
      origin influenza A/H1N1 in 2009), has tested the ability of virology laboratories
      to develop diagnostic tests to identify these viruses. Nucleic acid amplification
      tests (NATs) that first appeared two decades ago have been developed for both
      conventional and emerging viruses and now form the backbone of the clinical
      laboratory. NATs provide fast, accurate and sensitive detection of respiratory
      viruses and have significantly increased our understanding of the epidemiology of
      these viruses. Multiplex PCR assays have been introduced recently and several
      commercial tests are now available. The final chapter in the evolution of
      respiratory virus diagnostics will be the addition of allelic discrimination and
      detection of single nucleotide polymorphisms associated with antiviral resistance
      to multiplex assays. These resistance assays together with new viral load tests
      will enable clinical laboratories to provide physicians with important
      information for optimal treatment of patients.

PMID- 21073293
TI  - Current medical management of diabetic foot infections.
AB  - Foot infections are a serious complication of diabetes associated with
      substantial morbidity and occasional mortality. Antibiotic therapy for mild
      infections in patients who have not recently received antibiotic therapy can
      often be directed at just staphylococci and streptococci. Empiric therapy for
      infections that are chronic, moderate or severe, or that occur in patients who
      have failed previous antibiotic treatment, should usually be more broad spectrum.
      Bone infection also complicates a substantial percentage of diabetic foot wounds
      and increases the likelihood of treatment failure, requiring lower extremity
      amputation. An increasing body of evidence supports the effectiveness of
      nonsurgical treatment of diabetic foot osteomyelitis in selected patients,
      although the optimal choice of agent, route of administration and duration of
      therapy have yet to be defined. This article examines the potential role of
      standard and newer antibiotics that may be appropriate for treating diabetic foot
      infections, including ertapenem, vancomycin, moxifloxacin, daptomycin, telavancin
      and tigecycline, as well as several investigational agents, such as dalbavancin,
      ceftobiprole and nemonoxacin.

PMID- 21073294
TI  - Neuroschistosomiasis.
AB  - Neuroschistosomiasis, the infection of the CNS by Schistosoma spp., is a
      neglected and under-recognized complication of schistosomiasis. Cerebral and
      spinal neuroschistosomiasis can provoke severe disability. Neurological symptoms
      occur as a consequence of the immune reaction around the eggs deposited in the
      CNS. Cerebral neuroschistosomiasis may present with altered sensorium, headache,
      seizures and focal neurological deficit. Pseudotumoral and cerebellar
      neuroschistosomiasis may provoke intracranial hypertension and hydrocephalus.
      Brain-enhancing lesions with associated mass effect can be observed on MRI.
      Transverse myelitis and myeloradiculopathy affecting the conus medullaris and/or
      cauda equina are the most common spinal cord syndromes. Transverse myelitis can
      present as flaccid arreflexic paraplegia with sensory level and sphincter
      dysfunction. Praziquantel and corticoids have been successfully used to treat
      neuroschistosomiasis. Ventricle-peritoneal shunt may be necessary to treat
      hydrocephalus associated with tumor-like brain and/or cerebellar schistosomiasis.

PMID- 21073296
TI  - Increased shedding of soluble TNF-receptor 1 during hyperthermic TNF-alpha-based
      isolated limb perfusion.
AB  - PURPOSE: Hyperthermic isolated limb perfusion (HILP) with TNF-alpha and melphalan
      has high response rates in patients with soft tissue sarcomas (STS) or melanomas
      of the limbs. Its effectiveness is based on the destructive effect of TNF-alpha
      on the blood supply of the tumours. Shedding of soluble TNF-receptor (sTNF-R)
      negatively modulates the effects of TNF-alpha, whereas hyperthermia (HT) induces
      shedding. Here, we investigated whether sTNF-R shedding in response to HT occurs
      during HILP. MATERIAL AND METHODS: The serum levels of sTNFR-1 were measured in
      23 patients with HILP by obtaining serum from the extracorporeal and central
      circuits. The samples were taken from the patients under normothermic (37 degrees
      C) and hyperthermic (39 degrees C) conditions. Additionally, cell cultures of
      HUVEC, human fibrosarcoma cells and peripheral blood cells were used to confirm
      the effects of HT on sTNF-R1 shedding by ELISA and western blot. RESULTS: Under
      HT, levels of sTNF-R1 increased 23.5% in the extracorporeal circuit, but this
      increase was not observed in the systemic circuit. However, we could not confirm
      this effect using the cell culture model, where cellular TNF-R1 and sTNF-R1 of
      culture supernatants, respectively, were not significantly different between NT
      and HT conditions. CONCLUSIONS: HT is associated with an increase of sTNF-R1 in
      the extracorporeal circuit of perfused limbs. Interestingly, HT does not exhibit
      the same effect on cells cultured in vitro. Additional studies will be aimed at
      determining whether our findings have an impact in the clinic by analysing the
      relationship between TNF-R1 shedding and tumour response to HILP.

PMID- 21073297
TI  - Does low testosterone affect adaptive properties of adipose tissue in obese men?
AB  - Obesity and (pre)diabetes in males is associated with low serum testosterone and
      increased oestradiol levels. It is unknown whether these changes in sex steroids
      are part of a vicious circle resulting in an increase of risk for metabolic
      complications of obesity, or whether it presents merely an epiphenomenon. The
      risk for metabolic complications in obesity seems to be determined by adaptation
      and integrity of adipose tissue. It is unknown whether the typical changes in sex
      steroids seen in obese men are desirable or ominous with respect to these
      functions. However, it might be clinically relevant, as low serum testosterone
      can be treated, and well with different forms of interventional therapy. The
      present review provides a short summary on findings, obstacles and future
      research needed to gain better insight into consequences of changes in sex
      steroids for adaptation of adipose tissue in obese men.

PMID- 21073298
TI  - Finding Mount Everest and handling voids.
AB  - Evolutionary algorithms (EAs) are randomized search heuristics that solve
      problems successfully in many cases. Their behavior is often described in terms
      of strategies to find a high location on Earth's surface. Unfortunately, many
      digital elevation models describing it contain void elements. These are elements
      not assigned an elevation. Therefore, we design and analyze simple EAs with
      different strategies to handle such partially defined functions. They are
      experimentally investigated on a dataset describing the elevation of Earth's
      surface. The largest value found by an EA within a certain runtime is measured,
      and the median over a few runs is computed and compared for the different EAs.
      For the dataset, the distribution of void elements seems to be neither random nor
      adversarial. They are so-called semirandomly distributed. To deepen our
      understanding of the behavior of the different EAs, they are theoretically
      considered on well-known pseudo-Boolean functions transferred to partially
      defined ones. These modifications are also performed in a semirandom way. The
      typical runtime until an optimum is found by an EA is analyzed, namely bounded
      from above and below, and compared for the different EAs. We figure out that for
      the random model it is a good strategy to assume that a void element has a worse
      function value than all previous elements. Whereas for the adversary model it is
      a good strategy to assume that a void element has the best function value of all
      previous elements.

PMID- 21073299
TI  - Immediate implants after enucleation of an odontogenic keratocyst: an early
      return to function.
AB  - An odontogenic keratocyst is a unique cyst because of its locally aggressive
      behavior, high recurrence rate, and characteristic histologic appearance. In this
      article we present the case of a 22-year-old male patient with a large
      odontogenic keratocyst and describe his treatment with immediate dental implants.

PMID- 21073300
TI  - Understanding peri-implantitis: a strategic review.
AB  - The high survival rate of osseointegrated dental implants is well documented, but
      it is becoming increasingly clear that successfully integrated implants are
      susceptible to disease conditions that may lead to loss of the implant. Although
      placement and restoration usually are included in the domain of the periodontal,
      oral and maxillofacial surgery, or prosthetic specialist, given the increasing
      numbers of patients treated with osseointegrated fixtures, it is increasingly
      likely that maintenance of these implants by the general dentist will become much
      more common. However, the surrounding tissues may be subject to inflammatory
      conditions similar to periodontal disease and so require maintenance. This
      article discusses the background, cause, and diagnosis of peri-implant disease,
      as well as the maintenance, care, and treatment of peri-implant infection in
      osseointegrated implants.

PMID- 21073301
TI  - Malaria therapy: where do we stand, what next?

PMID- 21073302
TI  - Rapid diagnostics for influenza: what are the options?

PMID- 21073303
TI  - Prokaryotic taxonomy rules and nomenclature changes in the Mycobacterium chelonae
      abscessus group.

PMID- 21073306
TI  - The Australasian Society for Infectious Diseases Annual Scientific Meeting 2010.
AB  - The 2010 Australasian Society for Infectious Diseases Annual Scientific Meeting
      took place in May in the Northern Territory (Australia) and focussed on
      infections in the region. The meeting highlights included the changing spectrum
      of malaria and dengue in endemic regions, the latest on influenza epidemiology,
      multidrug-resistant organisms and infectious diseases in the Australian
      indigenous population. This was complemented by subspeciality interest group
      research encompassing mycobacterial disease, infection control, mycology and
      virology.

PMID- 21073307
TI  - Towards broad protection against Ebolaviruses.
AB  - The Ebola and Marburg viruses (from the filovirus family) induce deadly
      hemorrhagic fevers for which there is currently no licensed vaccine or treatment.
      Frequent outbreaks have occurred in sub-Saharan Africa, in humans and nonhuman
      primates over the last 15 years or so and constitute a major public health
      problem. Of particular concern, a new species of Ebolavirus recently emerged in
      Uganda, highlighting the high potential of these viruses to evolve and the need
      to develop 'broad-spectrum' vaccines against filoviruses. Hensley et al. used
      their well studied vaccine platform based on DNA vectors and recombinant,
      replication-defective, adenoviruses producing Ebolavirus glycoproteins to protect
      cynomolgus monkeys against a heterologous challenge with the new species. Further
      developments are required before this experimental approach could be adapted for
      field use in humans, but this study nevertheless constitutes a proof-of-concept
      for broad protection against Ebolaviruses.

PMID- 21073308
TI  - Regulation of genes involved in sugar uptake, glycolysis and lactate production
      in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum is a nonpathogenic, GC-rich, Gram-positive bacterium
      with a long history in the industrial production of amino acids. Recently, the
      species has become of increasing interest as a model bacterium for closely
      related, medically important pathogenic species such as Corynebacterium
      diphtheriae and Mycobacterium tuberculosis. In this article, recent advances in
      understanding of the C. glutamicum regulatory network of genes involved in
      carbohydrate metabolism are reviewed with regards to sugar uptake, glycolysis and
      lactate production.

PMID- 21073309
TI  - Cultivation of epithelial-associated microbiota by the immune system.
AB  - Mounting evidence supports the intuitive idea that many of the factors produced
      in defense of the epithelial surface, including mucin and secretory IgA, promote
      the growth of the commensal microbial flora, much the same as plant-derived
      mucoid substances support the growth of symbiotic microbes in the rhizosphere
      associated with roots. Thus, the 'defense' of the host epithelial surface often
      involves support and maintenance of microbial growth, despite an unfortunate
      tendency to view the immune system as an antagonist to the microbial flora. The
      perspective that the immune system supports the growth of a symbiotic microbiota
      has the potential to push forward our understanding of host-microbe interactions
      and to facilitate the development of new treatments for diseases associated with
      the microbiota.

PMID- 21073311
TI  - Retroviral vectors for gene therapy.
AB  - Since their first clinical trial 20 years ago, retroviral (gretroviral and
      lentiviral) vectors have now been used in more than 350 gene-therapy studies.
      Retroviral vectors are particularly suited for gene-correction of cells due to
      long-term and stable expression of the transferred transgene(s), and also because
      little effort is required for their cloning and production. Several monogenic
      inherited diseases, mostly immunodeficiencies, can now be successfully treated.
      The occurrence of insertional mutagenesis in some studies allowed extensive
      analysis of integration profiles of retroviral vectors, as well as the design of
      lentiviral vectors with increased safety properties. These new-generation vectors
      will enable us to continue the successful story of gene therapy, and treat more
      patients and even more complex diseases.

PMID- 21073310
TI  - Human papillomavirus: gene expression, regulation and prospects for novel
      diagnostic methods and antiviral therapies.
AB  - Human papillomaviruses (HPVs) cause diseases ranging from benign warts to
      invasive tumors. A subset of these viruses termed 'high risk' infect the cervix
      where persistent infection can lead to cervical cancer. Although many HPV genomes
      have been sequenced, knowledge of virus gene expression and its regulation is
      still incomplete. This is due in part to the lack, until recently, of suitable
      systems for virus propagation in the laboratory. HPV gene expression is
      polycistronic initiating from multiple promoters. Gene regulation occurs at
      transcriptional, but particularly post-transcriptional levels, including RNA
      processing, nuclear export, mRNA stability and translation. A close association
      between the virus replication cycle and epithelial differentiation adds a further
      layer of complexity. Understanding HPV mRNA expression and its regulation in the
      different diseases associated with infection may lead to development of novel
      diagnostic approaches and will reveal key viral and cellular targets for
      development of novel antiviral therapies.

PMID- 21073312
TI  - Salmonella genomic islands and antibiotic resistance in Salmonella enterica.
AB  - Antibiotic resistance in several Salmonella enterica serovars that cause
      gastrointestinal disease in humans is due to a set of related genomic islands
      carrying a class 1 integron, which carries the resistance genes. Salmonella
      genomic island 1 (SGI1), the first island of this type, was found in S. enterica
      serovar Typhimurium DT104 isolates, which are resistant to ampicillin,
      chloramphenicol, florfenicol, streptomycin, spectinomycin, sulfonamides and
      tetracycline. Several Salmonella serovars and Proteus mirablis have since been
      shown to harbor SGI1 or related islands carrying various sets of resistance genes
      and some distinct groups have emerged. SGI1 is an integrative mobilizable element
      and can be transferred experimentally into Escherichia coli. However, within
      serovars, isolates recovered from different parts of the world appear to be
      clonal, indicating that SGI1 movement may be rare. Potential reservoirs in food
      producing animals or in ornamental fish have been identified for some serovars.

PMID- 21073313
TI  - The Streptococcus pyogenes proteome: maps, virulence factors and vaccine
      candidates.
AB  - Streptococcus pyogenes is an important cause of human morbidity and mortality
      worldwide. A wealth of genomic information related to this pathogen has
      facilitated exploration of the proteome, particularly in response to
      environmental conditions thought to mimic various aspects of pathogenesis.
      Proteomic approaches are also used to identify immunoreactive proteins for
      vaccine development and to identify proteins that may induce autoimmunity. These
      studies have revealed new mechanisms involved in regulating the S. pyogenes
      proteome, which has opened up new avenues in the study of S. pyogenes
      pathogenesis. This article describes the methods used, and progress being made
      towards characterizing the S. pyogenes proteome, including studies seeking to
      identify potential vaccine candidates.

PMID- 21073314
TI  - Postgenomic strategies in antibacterial drug discovery.
AB  - During the last decade the field of antibacterial drug discovery has changed in
      many aspects including bacterial organisms of primary interest, discovery
      strategies applied and pharmaceutical companies involved. Target-based high
      throughput screening had been disappointingly unsuccessful for antibiotic
      research. Understanding of this lack of success has increased substantially and
      the lessons learned refer to characteristics of targets, screening libraries and
      screening strategies. The 'genomics' approach was replaced by a diverse array of
      discovery strategies, for example, searching for new natural product leads among
      previously abandoned compounds or new microbial sources, screening for synthetic
      inhibitors by targeted approaches including structure-based design and analyses
      of focused libraries and designing resistance-breaking properties into
      antibiotics of established classes. Furthermore, alternative treatment options
      are being pursued including anti-virulence strategies and immunotherapeutic
      approaches. This article summarizes the lessons learned from the genomics era and
      describes discovery strategies resulting from that knowledge.

PMID- 21073316
TI  - Prevention and treatment of malaria in pregnancy.
AB  - Malaria in pregnancy is a substantial public health issue in many tropical
      countries. However, its prevention and treatment have been hindered because of
      fears of adverse drug effects in pregnant women recruited to intervention
      studies. This article details the pharmacological agents and management
      strategies currently or potentially available for use in pregnant women with or
      at risk of malaria. There are deficiencies in pharmacokinetic, tolerability,
      safety and efficacy data for even well-established drugs and combinations. This
      can have serious implications for the design of rational dose regimens.
      Approaches such as intermittent preventive treatment are increasingly employed in
      endemic areas with proven benefits, but the emergence of parasite drug resistance
      means that new strategies and drug regimens should be continually evaluated.

PMID- 21073318
TI  - Particle size reduction and pharmacokinetic evaluation of a poorly soluble acid
      and a poorly soluble base during early development.
AB  - AIM: The aim of the present study was to find out if nanosuspensions were a
      better choice compared with microsuspensions, for the present substances with
      water solubility in the order of 2-3 MUM (pH 6.8, small intestinal pH) and no
      permeability limitations. The ambition was also to understand what the higher
      solubility in the stomach for BA99 means in terms of absorption properties of the
      substance. METHOD: The pharmacokinetic parameters of a poorly soluble acid (AC88)
      and a poorly soluble base (BA99) administered orally as nanosuspensions have been
      compared with those from microsuspensions using rat as in vivo species. RESULTS:
      A significant difference was observed between the two suspensions for AC88
      already at the lowest dose, 5 MUmol/kg (the particle size of the nanosuspensions
      and the microsuspensions was about 200 nm and 14 MUm, respectively). These
      results were further confirmed at a high dose (500 MUmol/kg). However, for BA99,
      there were no significant differences between the two formulations at any dose
      investigated (the particle size of the nanosuspensions and the microsuspensions
      was about 280 nm and 12 MUm, respectively). CONCLUSIONS: The study demonstrated a
      clear correlation between particle size and in vivo exposures for an acidic
      compound, the nanosuspensions providing the highest exposure. For a basic
      compound, on the other hand, with the present properties and doses, a
      microsuspension was sufficient. In the latter case, the higher solubility at
      gastric pH, because of the basic pK(a), limits the need for particle reduction.

PMID- 21073315
TI  - Protein export systems of Mycobacterium tuberculosis: novel targets for drug
      development?
AB  - Protein export is essential in all bacteria and many bacterial pathogens depend
      on specialized protein export systems for virulence. In Mycobacterium
      tuberculosis, the etiological agent of the disease tuberculosis, the conserved
      general secretion (Sec) and twin-arginine translocation (Tat) pathways perform
      the bulk of protein export and are both essential. M. tuberculosis also has
      specialized export pathways that transport specific subsets of proteins. One such
      pathway is the accessory SecA2 system, which is important for M. tuberculosis
      virulence. There are also specialized ESX export systems that function in
      virulence (ESX-1) or essential physiologic processes (ESX-3). The increasing
      prevalence of drug-resistant M. tuberculosis strains makes the development of
      novel drugs for tuberculosis an urgent priority. In this article, we discuss our
      current understanding of the protein export systems of M. tuberculosis and
      consider the potential of these pathways to be novel targets for tuberculosis
      drugs.

PMID- 21073319
TI  - Development of polyvinyl alcohol-gelatin membranes for antibiotic delivery in the
      eye.
AB  - AIM: The aim of the present study was to develop biosynthetic hybrid polymer
      based ocular insert for topical administration of antibiotics for treatment of
      ocular infections. METHODS: Ciprofloxacin hydrochloride-loaded three different
      inserts were prepared by solution casting method by esterification of a
      biopolymer (gelatin) with a synthetic polymer (polyvinyl alcohol, PVA).
      Esterification between PVA and gelatin was confirmed by Fourier transform
      infrared spectroscopy. RESULTS: Inserts were found to be wettable and swellable
      with simulated tear fluid and had a contact angle <50 degrees  with simulated
      tear fluid. Mechanical properties of PVA-gelatin (10:3 wt%) inserts included a
      maximal tensile strength of 8.6 +/- 2 MPa and the inserts showed adequate
      mucoadhesion with reconstituted mucin. In vitro drug release of ciprofloxacin
      hydrochloride for up to 24 hours was observed from the inserts. Inserts were
      found to be biocompatible using SIRC rabbit corneal epithelial cell line by
      sulforhodamine B assay and by Draize test in albino rabbits. Further inserts
      showed higher ocular penetration of sodium fluorescein in goat eye as compared to
      eyedrop solution. CONCLUSIONS: In brief, the study suggests that PVA-gelatin
      polymeric blends are promising as ocular inserts for prolonged release of
      antibiotic in the eye as compared to eyedrops. Such inserts may also be
      therapeutically beneficial for treatment of corneal ulcers and external ocular
      infections.

PMID- 21073320
TI  - The study on the preparation process of PEG pellets by vibration nozzle method.
AB  - BACKGROUND: Uniform size beads can be easily produced by vibration nozzle method.
      OBJECTIVE: In this article, the pellets of polyethylene glycol are prepared by a
      vibration nozzle machine. Thickness of nozzle wall, rotation speed of stirrer,
      and voltage of excitation are discussed in this article. RESULTS AND DISCUSSION:
      A nozzle wall of thickness <=0.1 mm is applied to decrease the adherence of jet.
      The stirring device with 20 rotations/min on the upper side of condensed column
      is used to disperse unsolidified polyethylene glycol pellets. The effect of
      parameters including vibration frequency f, jet velocity v, and voltage of
      excitation V on the average diameter d and standard deviation SD% are
      investigated by response surface methodology and Weber equation. A very good
      linear regression between d and v/f is presented under optimum V (in this article
      V = 3.0 V). Both high v and low SD% can also be obtained by optimum V.

PMID- 21073321
TI  - Investigation of drug release from pellets coated with different shellac types.
AB  - CONTEXT: Even though most commercially available shellac types meet the
      specifications of the pharmacopoeias, their physicochemical properties and thus
      drug release may vary considerably. So far a comparison of drug release from
      dosage forms coated with different shellac types has not been made. OBJECTIVE:
      Drug release from pellets coated with different shellac types was investigated
      and the data correlated to the physicochemical properties of shellac. METHODS:
      Theophylline pellets were coated with three different commercially available
      shellac types of Indian and Thai origin. The minimum coating level (CL) to
      achieve gastric resistance was determined for each shellac type. The drug release
      characteristics from the different formulations were correlated with the
      physicochemical properties of the shellac types such as pK(a), acid value, and
      intrinsic dissolution rate. RESULTS: Gastric resistance was achieved at
      comparatively low CLs for all investigated shellac types. At pH 7.4 all
      investigated formulations showed complete drug release within 45 minutes. Drug
      release at pH 6.8 was prolonged and occurred by swelling and drug diffusion
      through the coating layer. However, the required minimum CL and drug release
      profiles especially at pH 6.8 varied considerably. Of the investigated shellac
      types, the Thai shellac stands out providing both gastric resistance at low CLs
      and fast drug release at high pH 6.8. CONCLUSION: Although a prediction of the
      release characteristic could not be made from the pK(a), the intrinsic
      dissolution rate turned out to be a good indicator for the drug release behavior.

PMID- 21073322
TI  - Standardized in vitro drug release test for colloidal drug carriers using
      modified USP dissolution apparatus I.
AB  - BACKGROUND: Recently the use of colloidal carriers as drug delivery systems is
      gaining more attention. Evaluation of the in vitro drug release is considered an
      important step during the development and quality control of such systems.
      Therefore, there is a need for a standard test technique to study in vitro drug
      release from colloidal systems. METHODS: The glass basket dialysis method was
      performed by a modification to the USP dissolution apparatus I by replacing the
      baskets with glass cylinders closed at the lower end by dialysis membrane. This
      method was characterized for the essential test parameters and compared to the
      dialysis bags technique using different types of colloidal drug carriers, namely
      liposomes, polymeric, and lipid nanoparticles. RESULTS: The method proved to be
      more discriminating than the conventional dialysis bag method and allowed for
      better comparison between different formulation parameters or experimental
      conditions. In general, the design is easy to perform, simple, and available in
      all pharmaceutical laboratories under the same setup. CONCLUSION: The described
      method is a step toward standardized dissolution tests on colloidal drug delivery
      systems and the possible comparability of results.

PMID- 21073323
TI  - Optimization of the emulsification and solvent displacement method for the
      preparation of solid lipid nanoparticles.
AB  - OBJECTIVE: The essential aim of this article is to prepare solid lipid
      nanoparticles (SLNs) by emulsification and solvent displacement method and to
      determine the best process conditions to obtain submicron particles. METHODS: The
      emulsification and solvent displacement method is a modification of the well
      known emulsification-diffusion method, but without dilution of the system. The
      extraction of the partially water-miscible solvent from the emulsion globules is
      carried out under reduced pressure, which causes the diffusion of the solvent
      toward the external phase, with subsequent lipid aggregation in particles whose
      size will depend on the process conditions. The critical variables affecting the
      process, such as stirring rate, the proportion of phases in the emulsion, and the
      amount of stabilizer and lipid, were evaluated and optimized. RESULTS: By this
      method, it was possible to obtain a high yield of solids in the dispersion for
      the lipids evaluated (Compritol((r)) ATO 888, Geleol((r)), Gelucire((r)) 44/14,
      and stearic acid). SLNs of up to ~20 mg/mL were obtained for all lipids
      evaluated. A marked reduction in size, between 500 and 2500 rpm, was seen, and a
      transition from micro- to nanometric size was observed. The smaller particle
      sizes obtained were 113 nm for Compritol((r)) ATO 888, 70 nm for Gelucire((r))
      44/14, 210 nm for Geleol((r)), and 527 nm for stearic acid, using a rotor-stator
      homogenizer (Ultra-Turrax((r))) at 16,000 rpm. The best phase ratio
      (organic/aqueous) was 1 : 2. CONCLUSIONS: The process proposed in this study is a
      new alternative to prepare SLNs with technological potential.

PMID- 21073324
TI  - Preparation and evaluation of a self-emulsifying drug delivery system of
      etoposide-phospholipid complex.
AB  - AIM: The aim of this study was to develop a new phospholipid complex self
      emulsifying drug delivery system (PC-SEDDS) to enhance bioavailability of oral
      etoposide, a drug with poor water solubility. METHODS: Etoposide-phospholipid
      complex (EPC) was prepared by reacting etoposide and phospholipid in
      tetrahydrofuran and confirmed as a phospholipid compound by differential scanning
      calorimetry (DSC). Solubility of EPC and etoposide was determined in various
      vehicles. Pseudoternary phase diagrams were constructed to identify the efficient
      self-emulsification region of EPC-SEDDS, and the effects of oil concentration,
      drug loading, and aqueous media on droplet size were investigated. RESULTS: The
      optimal formulation of EPC-SEDDS was EPC:octyl and decyl monoglyceride
      (ODO):Cremopher EL:PEG-400 (1:20:48:32) (w/w/w/w). Compared with etoposide
      phospholipid complex suspension (EPCS) and etoposide suspension (ES), cumulative
      release of etoposide from EPC-SEDDS increased by 1.31 and 2.65 fold at 24 hours,
      respectively. Compared with ES, relative bioavailability of EPC-SEDDS, E-SEDDS,
      and EPCS after oral administration in rats was enhanced by 60.21-, 44.9-, and
      8.44- fold, respectively. CONCLUSIONS: The synergistic effect between PC and
      SEDDS contributed to the enhanced bioavailability of etoposide. It was concluded
      that PC-SEDDS proved to be a potential system for delivering orally administered
      hydrophobic compounds including etoposide.

PMID- 21073325
TI  - New formulation of in situ gelling Metolose-based liquid suppository.
AB  - CONTEXT: An in situ gelling liquid suppository is liquid at room temperature but
      forms a gel at body temperature. In our work, Metolose(r) SM-4000
      (methylcellulose) is studied that basically shows thermal gelation at 68 degrees
      C (2%, w/w). OBJECTIVE: The objective was to study the potency of different
      factors (concentration, pH, additives) to change the value of thermal gelation
      temperature (T (t)) for Metolose(r) to form an in situ gelling liquid
      suppository. MATERIALS AND METHODS: We studied the effect of Metolose(r)
      concentration, pH, and salts (sodium chloride, potassium chloride, sodium
      hydrogen carbonate, and sodium monohydrogen phosphate) on T (t) by viscosimetry.
      To choose the appropriate compound, in vitro drug release was examined. Rectal
      safety test was performed on rats in vivo after 12-hour application. RESULTS:
      Increasing the Metolose(r) concentrations (0.5-4%, w/w), T (t) can be decreased,
      but it also altered the consistency of gel. pH does not affect the T (t). The
      water-soluble salts allowed reducing the gelation temperature to 37 degrees C.
      Sodium monohydrogen phosphate in 4.5% concentration was found to be the most
      appropriate. The impact of examined factors on in vitro drug release of piroxicam
      from the in situ-formed gel was characterized according to Fickian diffusion.
      Metolose(r) and the chosen salt did not cause any morphological damage on the
      rectal tissues. DISCUSSION: According to our study, Metolose(r) has the physical
      and chemical potential to be used as base for liquid suppositories.

PMID- 21073326
TI  - In this issue: the immune monitoring and complexity of rnas; drugs inducing
      tolerogenic dcs; and harnessing dialysis-related immune dysfunction.

PMID- 21073327
TI  - Toll-like receptor 3: involvement with exogenous and endogenous RNA.
AB  - The recognition of pathogens is assigned to an evolutionarily conserved family of
      receptors, the Toll-like receptors (TLRs). The investigation of RNA-based
      immunology has been reinvigorated with the observation that TLR3s interact with
      RNA (dsRNA of viral origin, poly (I:C) and endogenous RNA). Many RNAs, therefore,
      join the list of endogenous ligands for TLRs. The further finding that nucleoside
      modification alters RNA-mediated TLR signaling presents a mechanism for the long
      observed differences in immunogenicity. The involvement of RNA modification in
      the pathogenesis of diseases, and its implications in the therapeutics, are still
      being studied, and will have important implications in the future.

PMID- 21073328
TI  - Novel findings in drug-induced dendritic cell tolerogenicity.
AB  - Dendritic cells (DCs) constitute a unique set of antigen-presenting cells (APCs),
      equipped with the potential to initiate strong immune responses as well as to
      critically regulate immunity. Tolerogenic or "alternatively activated" DCs show
      remarkable properties in regulating immune responses both in vitro and in vivo.
      Furthermore, tolerogenic DCs are now beginning to be tested in clinical studies.
      Use of pharmacological agents to induce maturation-resistant tolerogenic DCs is a
      popular approach. In this review, we will discuss already recognized, as well as
      recently discovered, potential pharmacological agents, their mechanism of action,
      and the way in which they induce tolerance in DCs.

PMID- 21073329
TI  - Bio-incompatibility and Th2 polarization during regular dialysis treatment.
AB  - Long-term hemodialysis treatment results in chronic monocyte activation with
      cytokine release. It generates Treg induction with potential immune dysfunction
      and associated clinical complications. Recent immunological data and preliminary
      clinical evidence suggest that synthetic polymers and vitamin E coated membranes
      are associated with a significant improvement in hemodialysis tolerance when
      compared to cellulose membranes. The aim of this review is to update cytokine
      release, T-cell polarization, and its clinical impact in patients under
      extracorporeal hemodialysis comparing traditional cellulose to synthetic/vitamin
      E coated membranes.

PMID- 21073330
TI  - The role of obesity as a modifying factor in patients undergoing non-surgical
      periodontal therapy.
AB  - BACKGROUND: Earlier studies have shown an association between obesity and
      periodontitis, which is mediated by cytokine production. The aim of this study is
      to assess the role of obesity as a modifying factor on periodontal clinical
      parameters and on circulating proinflammatory cytokine levels in subjects
      undergoing non-surgical periodontal treatment. METHODS: Twenty-seven obese
      subjects and 25 normal-weight subjects were enrolled in this study. Subjects in
      both groups had generalized chronic periodontitis. The periodontal parameters
      measured before and 3 months after non-surgical periodontal therapy were: visible
      plaque index, bleeding gingival index, bleeding on probing, probing depth, and
      clinical attachment level. In addition, subjects underwent anthropometric
      measurements and serum analyses of fasting glucose, glycated hemoglobin,
      interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and interferon
      gamma. RESULTS: Periodontal therapy significantly decreased visible plaque index,
      bleeding gingival index, bleeding on probing, probing depth of 4 to 6 mm, probing
      depth >=7 mm, clinical attachment level of 4 to 6 mm, and clinical attachment
      level >=7 mm in both groups (P <=0.05). Circulating proinflammatory cytokines
      significantly decreased in obese and normal-weight subjects after periodontal
      treatment (P <=0.05). However, interleukin-6 and tumor necrosis factor-alpha
      levels remained higher in obese subjects 3 months after treatment (P <=0.05).
      CONCLUSION: Obesity does not seem to play a negative role by interfering in the
      improvement of the periodontal clinical response or decreasing circulating
      proinflammatory cytokine levels after periodontal treatment.

PMID- 21073331
TI  - Accuracy of oral mucosal thickness measurements using spiral computed tomography.
AB  - BACKGROUND: Assessment of oral mucosal thickness is important in implant surgery;
      however, examining the soft tissue three dimensionally is difficult. A reamer
      method is invasive, and a non-invasive ultrasonic method produces only low
      resolution images depending on anatomic variations. The emerging technology of
      spiral computed tomography (CT) is an alternative to the conventional methods.
      Spiral CT has been a useful diagnostic tool in implant surgery. Although it
      delivers high radiation doses, spiral CT provides three-dimensional imaging of
      low-contrast structures. The purpose of the present study is to assess the
      accuracy of oral mucosal measurements using spiral CT. METHODS: Thickness of
      maxillary oral mucosa was measured in five cadavers. The measurement sites were
      set up in buccal, palatal, and middle of the crest in the missing tooth area in
      the incisor, canine, premolar, and molar regions. Each cadaver was exposed to
      spiral CT after installing the measurement guide. After that, each site was
      physically measured by reamer. Linear regression and correlation analysis were
      performed to describe the association between radiographic and physical
      measurements. RESULTS: A total of 114 measurements were performed with
      statistical analyses. Mean values and standard deviations of physical and
      radiographic measurements were 3.12 +/- 1.43 and 2.83 +/- 1.70 mm, respectively.
      The radiographic and physical measurements demonstrate strong correlation (r =
      0.90; P <0.01). Measurement error was 0.52 +/- 0.36 mm. According to the regions,
      the measurements in buccal, palatal, and missing tooth region depicted a
      significant correlation (r = 0.92, r = 0.85, and r = 0.91, respectively). The
      boundary of the bone and mucosa was indistinguishable at 23 buccal sites. Twenty
      three measurements that could not be distinguished with CT had a mean of 0.69 and
      standard deviation +/- 0.13 mm. CONCLUSIONS: The correlation between spiral CT
      and physical measurement was high except in sites of very thin mucosa. Spiral CT
      can be considered an alternative method for the measurement of oral mucosal
      thickness. Because of the higher radiation exposure, caution should be exercised
      and radiation dosage versus clinical benefit assessment is required.

PMID- 21073332
TI  - Influence of antiplatelet drugs in the pathogenesis of experimental periodontitis
      and periodontal repair in rats.
AB  - BACKGROUND: Platelets contain an array of biologic mediators that can modulate
      inflammation and repair processes including proinflammatory mediators and growth
      factors. Previous studies have shown that periodontitis and periodontal repair
      are associated with platelet activation. We hypothesized that drug-induced
      platelet inactivation may interfere in the processes of inflammation and repair
      in experimental periodontitis in rats by suppressing the release of biologic
      mediators from platelets to the site of injury. METHODS: To measure the effects
      on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30
      mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for
      15 days. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and
      thromboxane A(2) levels were measured by enzyme-linked immunosorbent assay. To
      evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were
      removed after 15 days of periodontitis induction, and Asp or Clo were
      administered beginning the following day for 15 days. Periodontal repair was
      assessed by microcomputed tomography. RESULTS: On periodontitis phase, Asp and
      Clo significantly reduced levels of TNF-alpha and Il-6 (P <0.05), but only Asp
      decreased thromboxane A(2) (P <0.05). Asp and Clo decreased inflammatory
      infiltration; however, this reduction was more pronounced with Clo treatment (P
      <0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone
      resorption. During the repair phase and after removal of the ligatures,
      microcomputed tomography analysis demonstrated that treatment with Asp and Clo
      did not impair alveolar bone repair. CONCLUSION: Systemic administration of Asp
      and Clo attenuates the inflammation associated with periodontitis without
      affecting the repair process when stimulus is removed.

PMID- 21073333
TI  - Stromal cell-immune cell interactions.
AB  - Interaction between different types of hematopoietic cells is essential for
      proper functioning of the immune system. For instance, the cytokines produced by
      antigen-presenting dendritic cells will determine the type of T cell response
      that is induced. However, hematopoietic cells are also strongly influenced by the
      surrounding nonhematopoietic cells. The cells that form these microenvironments
      are collectively called stromal cells. Here, we focus on the stromal cells
      present within secondary lymphoid organs and discuss their importance for various
      aspects of the immune system.

PMID- 21073334
TI  - Update on sleep and its disorders.
AB  - Inadequate sleep and sleep disorders have important adverse consequences on
      multiple systems. This review covers three areas: (a) Genetic determinants of
      sleep disorders. Common gene variants with small effects have been identified for
      both restless legs syndrome and narcolepsy with cataplexy. Rare variants with
      large effects have been found in familial phase advance syndrome and in subjects
      with short sleep durations. (b) Obstructive sleep apnea (OSA). OSA is an
      oxidative stress disorder. Prospective cohort studies show an increased risk of
      cardiovascular events in patients with untreated severe OSA. (c) The impact of
      sleep disorders on obesity and diabetes. Inadequate sleep results in changes in
      insulin resistance and in hormone levels leading to increases in appetite. Hence,
      inadequate sleep is associated with development of obesity. OSA is also an
      independent risk factor for insulin resistance; treatment of OSA can improve
      insulin sensitivity.

PMID- 21073335
TI  - Regulation of bone mass by serotonin: molecular biology and therapeutic
      implications.
AB  - The molecular elucidation of two human skeletal dysplasias revealed that they are
      caused by an increase or a decrease in the synthesis of serotonin by
      enterochromaffin cells of the gut. This observation revealed a novel and powerful
      endocrine means to regulate bone mass. Exploiting these findings in the
      pharmacological arena led to the demonstration that inhibiting synthesis of gut
      derived serotonin could be an effective means to treat low-bone-mass diseases
      such as osteoporosis.

PMID- 21073336
TI  - How the genetics of deafness illuminates auditory physiology.
AB  - Although the basic principles underlying the function of the peripheral auditory
      system have been known for many years, the molecules required for hearing have
      hitherto remained elusive. Genetic approaches have recently provided unparalleled
      molecular insight into how the hair bundle, the hair cell's mechanosensory
      organelle, forms and functions. We discuss how the proteins encoded by the Usher
      syndrome type 1 genes form molecular complexes required for hair-bundle
      development and for gating the mechanotransducer channel. We show how mouse
      models for nonsyndromic forms of deafness involving genes encoding Triobp and
      stereocilin reveal, respectively, the way stereocilia rootlets contribute to the
      hair bundle's mechanical properties and how the hair bundle produces suppressive
      masking, a property that contributes to speech intelligibility. Finally, we
      examine how mutations in the genes encoding alpha- and beta-tectorin reveal
      multiple roles for the tectorial membrane, an extracellular matrix unique to the
      cochlea, in stimulating hair bundles.

PMID- 21073337
TI  - The pathobiology of arrhythmogenic cardiomyopathy.
AB  - This review highlights current knowledge about arrhythmogenic cardiomyopathy and
      considers clinical, pathological, genetic, biomechanical, and pathophysiological
      aspects of disease pathogenesis. Although relatively uncommon, arrhythmogenic
      cardiomyopathy is of particular interest as a model system for study. It is
      caused in at least half of all cases by single-gene mutations that provide direct
      entry points into studies designed to elucidate mechanisms of disease. These
      mutations involve proteins that form desmosomes, directly implicating altered
      cellular biomechanical properties in disease pathogenesis and providing
      opportunities to investigate more broadly the ways in which abnormal cell and
      tissue biomechanics induce cardiac myocyte injury and alter cell biology. The
      highly arrhythmogenic phenotype is a cardinal feature of the disease. A more
      complete understanding of the pathogenesis of this aspect of arrhythmogenic
      cardiomyopathy may shed light onto the basic mechanisms underlying lethal
      ventricular arrhythmias and sudden cardiac death in more common forms of heart
      disease.

PMID- 21073338
TI  - Retinoids, retinoic acid receptors, and cancer.
AB  - Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling
      molecules) induce the differentiation of various types of stem cells. Nuclear
      retinoic acid receptors mediate most but not all of the effects of retinoids.
      Retinoid signaling is often compromised early in carcinogenesis, which suggests
      that a reduction in retinoid signaling may be required for tumor development.
      Retinoids interact with other signaling pathways, including estrogen signaling in
      breast cancer. Retinoids are used to treat cancer, in part because of their
      ability to induce differentiation and arrest proliferation. Delivery of retinoids
      to patients is challenging because of the rapid metabolism of some retinoids and
      because epigenetic changes can render cells retinoid resistant. Successful cancer
      therapy with retinoids is likely to require combination therapy with drugs that
      regulate the epigenome, such as DNA methyltransferase and histone deacetylase
      inhibitors, as well as classical chemotherapeutic agents. Thus, retinoid research
      benefits both cancer prevention and cancer treatment.

PMID- 21073339
TI  - Pathogenesis of liver fibrosis.
AB  - Liver fibrosis is a major cause of morbidity and mortality worldwide due to
      chronic viral hepatitis and, more recently, from fatty liver disease associated
      with obesity. Hepatic stellate cell activation represents a critical event in
      fibrosis because these cells become the primary source of extracellular matrix in
      liver upon injury. Use of cell-culture and animal models has expanded our
      understanding of the mechanisms underlying stellate cell activation and has shed
      new light on genetic regulation, the contribution of immune signaling, and the
      potential reversibility of the disease. As pathways of fibrogenesis are
      increasingly clarified, the key challenge will be translating new advances into
      the development of antifibrotic therapies for patients with chronic liver
      disease.

PMID- 21073340
TI  - Mechanisms of leukocyte transendothelial migration.
AB  - Neither the innate nor adaptive immune system "responds" unless leukocytes cross
      blood vessels. This process occurs through diapedesis, in which the leukocyte
      moves in an ameboid fashion through tightly apposed endothelial borders and, in
      some cases, through the endothelial cell itself. This review focuses on the
      active role of the endothelial cell in diapedesis. Several mechanisms play a
      critical role in transendothelial migration, including signals derived from
      clustering of apically disposed intercellular adhesion molecule 1 and vascular
      cell adhesion molecule 1, disruption or loosening of adherens junctions, and
      targeted recycling of platelet/endothelial cell adhesion molecule and other
      molecules from the recently described lateral border recycling compartment.
      Surprisingly, many of the same molecules and mechanisms that regulate
      paracellular migration also control transcellular migration. A hypothesis that
      integrates the various known mechanisms of transmigration is proposed.

PMID- 21073341
TI  - Biomedical differences between human and nonhuman hominids: potential roles for
      uniquely human aspects of sialic acid biology.
AB  - Although humans are genetically very similar to the evolutionarily related
      nonhuman hominids (chimpanzees, bonobos, gorillas, and orangutans), comparative
      studies suggest a surprising number of uniquely human differences in the
      incidence and/or severity of biomedical conditions. Some differences are due to
      anatomical changes that occurred during human evolution. However, many cannot be
      explained either by these changes or by known environmental factors. Because
      chimpanzees were long considered models for human disease, it is important to be
      aware of these differences, which appear to have been deemphasized relative to
      similarities. We focus on the pathophysiology and pathobiology of biomedical
      conditions that appear unique to humans, including several speculative
      possibilities that require further study. We pay particular attention to the
      possible contributions of uniquely human changes in the biology of cell-surface
      sialic acids and the proteins that recognize them. We also discuss the metabolic
      incorporation of a diet-derived nonhuman sialic acid, which generates a novel
      xeno-autoantigen reaction, and chronic inflammation known as xenosialitis.

PMID- 21073342
TI  - Mesenchymal stem cells: mechanisms of inflammation.
AB  - In adults, human mesenchymal stem cells (hMSCs) are found in vivo at low
      frequency and are defined by their capacity to differentiate into bone,
      cartilage, and adipose tissue, depending on the stimuli and culture conditions
      under which they are expanded. Although MSCs were initially hypothesized to be
      the panacea for regenerating tissues, MSCs appear to be more important in
      therapeutics to regulate the immune response invoked in settings such as tissue
      injury, transplantation, and autoimmunity. MSCs have been used therapeutically in
      clinical trials and subsequently in practice to treat graft-versus-host disease
      following bone marrow transplantation. Reports of successful immune modulation
      suggest efficacy in a wide range of autoimmune conditions, such as demyelinating
      neurological disease (multiple sclerosis), systemic lupus erythematosus, and
      Crohn's disease, among others. This review provides background information about
      hMSCs and also describes their putative mechanisms of action in inflammation. We
      provide a summary of ongoing clinical trials to allow (a) full comprehension of
      the range of diseases in which hMSC therapy may be beneficial and (b)
      identification of gaps in our knowledge about the mechanisms of action of
      therapeutic MSCs in disease.

PMID- 21073343
TI  - Splinting osseointegrated implants and natural teeth in partially edentulous
      patients: a systematic review of the literature.
AB  - Dental implants in partially edentulous patients are a predictable therapeutic
      option. In patients with reduced bone volume, tooth-to-implant connected
      prostheses have been described as a treatment option. In this systematic review,
      the incidence of biologic and technical complications and the long-term survival
      rates of tooth-implant supported fixed partial dentures (FPDs) are analyzed. In
      cases where a natural tooth is connected with an implant to support a FPD, a
      rigid connection should be preferred.

PMID- 21073344
TI  - Population growth of soybean aphid, Aphis glycines, under varying levels of
      predator exclusion.
AB  - Although soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), has
      caused economic damage in several Midwestern states, growers in Missouri have
      experienced relatively minor damage. To evaluate whether existing predatory
      insect populations are capable of suppressing or preventing soybean aphid
      population growth or establishment in Missouri, a predator exclusion study was
      conducted to gauge the efficacy of predator populations. Three levels of predator
      exclusion were used; one that excluded all insects (small mesh), one that
      excluded insects larger than thrips (medium mesh), and one that excluded insects
      larger than Orius insidiosus (Say) (Hemiptera: Anthocoridae), a principal
      predator (large mesh). Along with manipulating predator exposure, timing of aphid
      arrival (infestation) was manipulated. Three infestation times were studied;
      vegetative (V5), beginning bloom (R1), and beginning pod set (R3). Timing of
      aphid and predator arrival in a soybean field may affect the soybean aphid's
      ability to establish and begin reproducing. Cages infested at V5 and with
      complete predator exclusion reached economic threshold within two weeks, while
      cages with predators reached economic threshold in four and a half weeks. Cages
      infested at R1 with complete predator exclusion reached economic threshold within
      five weeks; cages with predators reached economic threshold within six weeks.
      Cages infested at R3 never reached threshold (with or without predators). The
      predator population in Missouri seems robust, capable of depressing the growth of
      soybean aphid populations once established, and even preventing establishment
      when the aphid arrived late in the field.

PMID- 21073345
TI  - Molecular cloning, expression profile and 5' regulatory region analysis of two
      chemosensory protein genes from the diamondback moth, Plutella xylostella.
AB  - Chemosensory proteins play an important role in transporting chemical compounds
      to their receptors on dendrite membranes. In this study, two full-length cDNA
      codings for chemosensory proteins of Plutella xylostella (Lepidoptera:
      Plutellidae) were obtained by RACE-PCR. PxylCSP3 and Pxyl-CSP4, with GenBank
      accession numbers ABM92663 and ABM92664, respectively, were cloned and sequenced.
      The gene sequences both consisted of three exons and two introns. RT-PCR analysis
      showed that Pxyl-CSP3 and Pxyl-CSP4 had different expression patterns in the
      examined developmental stages, but were expressed in all larval stages.
      Phylogenetic analysis indicated that lepidopteran insects consist of three
      branches, and Pxyl-CSP3 and Pxyl-CSP4 belong to different branches. The
      5'regulatory regions of Pxyl-CSP3 and Pxyl-CSP4 were isolated and analyzed, and
      the results consist of not only the core promoter sequences (TATA-box), but also
      several transcriptional elements (BR-C Z4, Hb, Dfd, CF2-II, etc.). This study
      provides clues to better understanding the various physiological functions of
      CSPs in P. xylostella and other insects.

PMID- 21073346
TI  - Wasp hawking induces endothermic heat production in guard bees.
AB  - When vespine wasps, Vespa velutina Lepeletier (Hymenoptera: Vespidae), hawk
      (capture) bees at their nest entrances alerted and poised guards of Apis cerana
      cerana F. and Apis mellifera ligustica Spinola (Hymenoptera: Apidae) have average
      thoracic temperatures slightly above 24 degrees  C. Many additional worker bees
      of A. cerana, but not A. mellifera, are recruited to augment the guard bee cohort
      and begin wing-shimmering and body-rocking, and the average thoracic temperature
      rises to 29.8 +/- 1.6 degrees  C. If the wasps persist hawking, about 30 guard
      bees of A. cerana that have raised their thoracic temperatures to 31.4 +/- 0.9
      degrees  C strike out at a wasp and form a ball around it. Within about three
      minutes the core temperature of the heat-balling A. cerana guard bees reaches
      about 46 degrees  C, which is above the lethal limit of the wasps, which are
      therefore killed. Although guard bees of A. mellifera do not exhibit the serial
      behavioural and physiological changes of A. cerana, they may also heat-ball
      hawking wasps. Here, the differences in the sequence of changes in the behaviour
      and temperature during "resting" and "heat-balling" by A. cerana and A. mellifera
      are reported.

PMID- 21073347
TI  - Influence of fungal odor on grooming behavior of the termite, Coptotermes
      formosanus.
AB  - The termite Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae) protects
      itself from entomopathogenic fungus by mutual grooming behavior. C. formosanus
      removes foreign organisms, such as fungal conidia, from the body surface of its
      nestmates by mutual grooming behavior and eating them. The conidia removal rate
      from the body surface differed according to the isolate of entomopathogenic fungi
      (Beauveria brongniartii 782, Paecilomyces fumosoroseus K3, and Metarhizium
      anisopliae 455), and the removal rate of the fungal isolates seemed to depend on
      feeding preference, which was determined using paper discs moistened with a
      fungal suspension. In addition, it was found that C. formosanus without antennae
      groomed their nestmates more frequently than those with antennae. Consequently,
      it seems that C. formosanus antennae detect substances without touching, such as
      via odor, and it affects the efficiency of grooming behavior. The results of
      single sensillum recording support the hypothesis that C. formosanus are capable
      of distinguishing three species of fungi by their odors.

PMID- 21073351
TI  - Nilotinib for the treatment of Philadelphia-chromosome-positive chronic myeloid
      leukemia.
AB  - IMPORTANCE OF THE FIELD: Although the introduction of imatinib revolutionized the
      management of chronic myeloid leukemia (CML), some patients exhibit resistance or
      intolerance to the drug. Nilotinib induces high and rapid rates of cytogenetic
      and molecular responses. With recent approval for newly diagnosed patients with
      chronic phase CML, the current algorithm for treatment will probably be
      transformed. AREAS COVERED IN THIS REVIEW: This review will describe evaluations
      of nilotinib in all phases of CML from 1995 to the present. Early preclinical
      data and Phase I, Phase II and Phase III evaluations will demonstrate the role of
      nilotinib in newly diagnosed CML, as well as in imatinib-resistant or imatinib
      intolerant disease. WHAT THE READER WILL GAIN: Mutations in the BCR-ABL kinase
      domain are responsible for the majority of resistance to imatinib. In comparison
      with imatinib, nilotinib displays increased selectivity and potency at inhibiting
      proliferation of BCR-ABL expressing cells. Although several mutations, including
      T315I, remain resistant to nilotinib, activity in all phases of CML has been
      reported. TAKE HOME MESSAGE: Nilotinib induces high and rapid rates of
      cytogenetic and molecular response, with less progression to advanced forms of
      disease compared with imatinib. Considering that the rapid achievement of these
      clinical milestones has been associated with positive long-term outcomes,
      nilotinib as initial therapy in patients with CML in chronic phase represents the
      future in CML treatment. Longer follow-up is necessary to recognize survival
      advantages.

PMID- 21073353
TI  - Bazedoxifene when paired with conjugated estrogens is a new paradigm for
      treatment of postmenopausal women.
AB  - IMPORTANCE OF THE FIELD: The concept of the tissue selective estrogen complex
      (TSEC) combining a selective estrogen receptor modulator (SERM) with one or more
      estrogens, aims to provide comparable efficacy to combination estrogen and
      progestin therapy for symptomatic menopausal women with a uterus without the need
      for a progestin. AREAS COVERED IN THIS REVIEW: Published multi-center randomized
      blinded clinical trials with bazedoxifene alone and paired in combination with
      conjugated estrogens show an effect in hot flashes, vaginal atrophy, quality of
      life measures, sleep, bone density, and breast and uterine safety. WHAT THE
      READER WILL GAIN: A new concept for menopausal women, bazedoxifene with
      conjugated estrogens (BZA-CE) TSEC, appears to provide the selective benefits of
      a SERM with additional benefits of estrogen without the need for a progestin.
      Preclinical studies with bazedoxifene alone showed that it was antagonistic in
      the uterine and breast tissue while an agonist in the bone. Phase II and III
      clinical studies of BZA-CE reveal relief from hot flashes and vaginal atrophic
      changes, and improvement in bone density, quality of life and sleep without
      breast or uterine stimulation. TAKE HOME MESSAGE: Bazedoxifene paired with
      conjugated estrogens in postmenopausal women relieves vasomotor symptoms and
      vulvovaginal atrophic changes with prevention of bone loss. Adverse events
      include a twofold increase risk of venous thrombosis. No evidence of stimulation
      of the breast, uterus or ovary was seen.

PMID- 21073352
TI  - Targeting the embryonic gene Cripto-1 in cancer and beyond.
AB  - IMPORTANCE OF THE FIELD: Emerging evidence has clearly implicated an
      inappropriate activation of embryonic regulatory genes during cell transformation
      in adult tissues. An example of such a case is the embryonic gene Cripto-1.
      Cripto-1 is critical for embryonic development and is considered a marker of
      undifferentiated embryonic stem cells. Critpo-1 is expressed at low levels in
      adult tissues, but is re-expressed at a high frequency in a number of different
      types of human carcinomas, therefore, representing an attractive therapeutic
      target in cancer. AREA COVERED IN THIS REVIEW: This review surveys different
      approaches that have been used to target Cripto-1 in cancer as reflected by the
      relevant patent literature as well as peer-reviewed publications. Potential
      involvement and targeting of Cripto-1 in neurodegenerative and degenerative
      muscle diseases are also discussed. WHAT THE READER WILL GAIN: The reader will
      gain an overview of different mAbs, vaccines or oligonucleotides antisense
      targeting Cripto-1. A humanized anti-Cripto-1 antibody is currently being tested
      in a Phase I clinical trial in cancer patients. TAKE HOME MESSAGE: Targeting
      Cripto-1 in human tumors has the potential to eliminate not only differentiated
      cancer cells but also destroy an undifferentiated subpopulation of cancer cells
      with stem-like characteristics that support tumor initiation and self-renewal.

PMID- 21073354
TI  - Do indicated preventive interventions for depression represent good value for
      money?
AB  - OBJECTIVE: The prevention of depression is of growing interest to researchers and
      policy makers. However, the question of whether interventions designed to prevent
      depression provide value for money at a population level remains largely
      unanswered. The current study assesses the cost-effectiveness of two indicated
      interventions designed to prevent depression: a brief psychological intervention
      based on bibliotherapy and a more comprehensive group-based psychological
      intervention following opportunistic screening for sub-syndromal depression in
      general practice. METHOD: Economic modelling using a cost utility framework was
      used to assess the incremental cost effectiveness ratios (ICERs) of the two
      interventions within the Australian population context, modelled as add-ons to
      current practice. The perspective was the health sector and outcomes were
      measured using disability-adjusted life years (DALYs). Uncertainty was measured
      using probabilistic uncertainty testing and important model assumptions were
      tested using univariate sensitivity testing. RESULTS: The brief bibliotherapy
      intervention had an ICER of AU$8600 per DALY and the group-based psychological
      intervention had an ICER of AU$20 000 per DALY. The majority of the uncertainty
      simulations for both interventions fell below the cost-effectiveness threshold
      value of $50 000 per DALY. Extensive sensitivity testing showed that the results
      were robust to the assumptions made in the analyses. CONCLUSIONS: Following
      screening in general practice, both psychological interventions, particularly
      brief bibliotherapy, appear to be good value for money and worthy of further
      evaluation under routine care circumstances. Acceptability issues associated with
      such interventions, particularly to primary care practitioners as providers of
      the interventions and health system administrators, also need to be considered
      before wide-scale adoption is contemplated.

PMID- 21073355
TI  - Stem cell transplantation as a biological therapy for peripheral T-cell
      lymphomas.
AB  - IMPORTANCE OF THE FIELD: Peripheral T-cell lymphomas (PTCL) are a heterogeneous
      group of non-Hodgkin's lymphomas in which conventional chemotherapy has been
      characterized by poor outcomes when compared with most aggressive B-cell
      lymphomas. Autologous, and to a lesser extent allogeneic, hematopoietic stem-cell
      transplant (HSCT) have been advocated as potential means to improve and
      consolidate remissions in PTCL. AREAS COVERED IN THIS REVIEW: Given the absence
      of large-scale randomized clinical controlled trials of transplantation for PTCL,
      we review existing data addressing the role and timing of HSCT in PTCL. WHAT THE
      READER WILL GAIN: A detailed overview of the available data of overall and
      progression-free survival associated with HSCT in PTCL with discussion of
      existing studies, data on determinants of HSCT outcome in PTCL, and future
      directions for research. TAKE HOME MESSAGE: The optimal roles and timing of HSCT
      in PTCL remain unclear. Accordingly, clinicians are encouraged to register their
      patients in PTCL registry studies and enroll them in clinical trials
      investigating the role of HSCT. Risk-adapted treatment strategies utilizing
      identified prognostic parameters may provide future means for identifying the
      optimal use of HSCT for patients with PTCL, but additional studies are needed
      before such approaches can be routinely applied.

PMID- 21073356
TI  - Prothrombotic mutations, family history and the risk of thrombosis in
      postmenopausal women: implications for hormone replacement therapy.
AB  - OBJECTIVE: Hormone replacement therapy (HRT) is acknowledged as the gold standard
      for the alleviation of climacteric vasomotor symptoms. Prothrombotic genetic
      variants have been suggested to increase thrombotic risk among HRT users. The aim
      of the study was to determine whether a positive family history may identify a
      genetic predisposition for thrombosis in women before prescribing HRT. METHODS:
      From January 2005 to May 2009, we consecutively enrolled 145 asymptomatic women
      (mean age 51.2 +/- 5.4 years) without previous episodes of venous and/or arterial
      thrombosis referred to our Genetics Research Unit before starting HRT. A detailed
      family history was reconstructed and we identified 48 women (33.1%) with a
      positive family history, defined as venous thromboembolism and/or stroke or heart
      attack, in first-degree relatives before 60 years for men and 65 years for women.
      A group of 121 women (mean age 54.0 +/- 9.1 years) with an episode of venous
      and/or arterial thrombosis was also included. Genetic screening for factor V
      Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase C677T
      polymorphisms was performed. RESULTS: The frequency of factor V Leiden or
      prothrombin G20210A mutations was significantly higher both in asymptomatic women
      with a positive family history (16.7% vs. 2.1%, p = 0.001) and in patients with
      thrombosis (12.4% vs. 2.1%; p = 0.005) compared with asymptomatic women without a
      family history. Multivariate regression analysis showed a synergic effect between
      the presence of one prothrombotic mutation and family history on the risk of
      thrombosis (odds ratio 3.7, 95% confidence interval 1.9-7.2). CONCLUSIONS: A
      positive family history of thrombosis is a sensitive indicator for selected
      genetic testing in high-risk women before starting HRT.

PMID- 21073357
TI  - Afamelanotide, an agonistic analog of alpha-melanocyte-stimulating hormone, in
      dermal phototoxicity of erythropoietic protoporphyria.
AB  - IMPORTANCE OF THE FIELD: Afamelanotide, an alpha-melanocyte stimulating hormone
      (MSH) agonistic analog is a first-in-class therapeutic. Its application to
      protoporphyria (PP), a disease associated with absolute sunlight-intolerance is
      discussed. AREAS COVERED IN THIS REVIEW: The genetics and existing therapy of the
      inherited disease PP comprising both erythropoietic protoporphyria and X-linked
      dominant protoporphyria. The physiological and pharmacological actions of alpha
      MSH and afamelanotide including receptor-mediated intracellular signaling and
      effects of receptor polymorphisms. Adverse effects and safety issues. WHAT THE
      READER WILL GAIN: The clinical severity and the necessity for an effective
      therapy for the rare disease PP are illustrated by a short, up-to-date portrait.
      A condensed description of clinically important aspects of alpha-MSH signaling,
      physiological, pharmacological and safety issues of afamelanotide applied to
      humans and the rational for its potential efficacy in PP are given. The different
      trials of afamelanotide in PP and their most recent results are discussed. TAKE
      HOME MESSAGE: Although early, results of the first trials of afamelanotide for PP
      are promising and the risk-safety profile appears favorable today. We expect
      afamelanotide and analogs thereof to be a prospective therapeutic tool in light
      related skin diseases, and in future this drug class might prove effectiveness in
      other medical conditions.

PMID- 21073358
TI  - Therapeutic potential of adenoviral vectors for delivery of expressed RNAi
      activators.
AB  - IMPORTANCE OF THE FIELD: Harnessing RNA interference (RNAi) to silence pathology
      causing genes has shown promise as a mode of therapy. The sustained gene
      inhibition that may be achieved with expressed sequences is potentially useful
      for treatment of chronic viral infections, but efficient and safe delivery of
      these sequences remains a challenge. It is generally recognized that there is no
      ideal vector for all therapeutic RNAi applications, but recombinant adenovirus
      vectors are well suited to hepatic delivery of expressed RNAi activators. AREAS
      COVERED IN THIS REVIEW: Adenoviruses are hepatotropic after systemic
      administration, and this is useful for delivering expressed RNAi activators that
      silence pathology-causing genes in the liver. However, drawbacks of adenoviruses
      are toxicity and diminished efficacy, which result from induction of innate and
      adaptive immune responses. In this review, the advantages and hurdles facing
      therapeutic application of adenoviral vectors for liver delivery of RNAi
      effectors are covered. WHAT THE READER WILL GAIN: Insights into adenovirus
      vectorology and the methods that have been used to make these vectors safer for
      advancing clinical application of RNAi-based therapy. TAKE HOME MESSAGE:
      Adenoviruses are very powerful hepatotropic vectors. To make adenoviruses more
      effective for clinical use, polymer conjugation and deletion of viral vector
      sequences have been used successfully. However, further modifications to
      attenuate immunostimulation as well as improvements in large-scale production are
      necessary before the therapeutic potential of adenovirus-mediated delivery of
      RNAi activators is realized.

PMID- 21073359
TI  - Single-molecule fluorescence resonance energy transfer techniques on rotary ATP
      synthases.
AB  - Conformational changes of proteins can be monitored in real time by fluorescence
      resonance energy transfer (FRET). Two different fluorophores have to be attached
      to those protein domains which move during function. Distance fluctuations
      between the fluorophores are measured by relative fluorescence intensity changes
      or fluorescence lifetime changes. The rotary mechanics of the two motors of
      F(o)F(1)-ATP synthase have been studied in vitro by single-molecule FRET. The
      results are summarized and perspectives for other transport ATPases are
      discussed.

PMID- 21073360
TI  - Physical strain of comfortable walking in children with mild cerebral palsy.
AB  - PURPOSE: To evaluate the physical strain of comfortable walking in children with
      mild cerebral palsy (CP) in comparison to typically developing (TD) children.
      Physical strain was defined as the oxygen uptake during walking (VO(2walk))
      expressed as a percentage of their maximal aerobic capacity (VO(2peak)). METHOD:
      Eighteen children (aged 8-16 years) participated, including eight ambulant
      children (four girls, four boys) with mild spastic CP (three hemiplegia, five
      diplegia, GMFCS I: n = 7 and II: n = 1) and 10 TD children. VO(2walk) was
      measured during 5 min of walking on an indoor track at comfortable walking speed.
      VO(2peak) was measured in a shuttle run test. RESULTS: VO(2walk) was
      significantly higher in CP (19.7 (2.8) ml/kg/min) compared to TD (16.8 (3.6)
      ml/kg/min, p = 0.033), while walking speed did not differ significantly between
      groups. VO(2peak) was significantly lower in CP (37.2 (2.2) ml/kg/min) compared
      to TD (45.0 (5.3) ml/kg/min, p = 0.001). Consequently, the physical strain during
      walking was significantly higher in CP (52 (7.7) %) compared to TD (36 (8.4) %, p
      = 0.001). CONCLUSIONS: The higher physical strain during comfortable walking of
      children with mild CP compared to TD children may be related to reported problems
      with fatigue in this population, and suggest a need for physical aerobic training
      programmes.

PMID- 21073361
TI  - Systematic literature review on ICF from 2001 to 2009: its use, implementation
      and operationalisation.
AB  - PURPOSE: To present a systematic literature review on the state of the art of the
      utilisation of the International Classification of Functioning, Disability and
      Health (ICF) since its release in 2001. METHOD: The search was conducted through
      EMBASE, MEDLINE and PsychInfo covering the period between 2001 and December 2009.
      Papers were included if ICF was mentioned in title or abstract. Papers focussing
      on the ICF-CY and clinical research on children and youth only were excluded.
      Papers were assigned to six different groups covering the wide scenario of ICF
      application. RESULTS: A total of 672 papers, coming from 34 countries and 211
      different journals, were included in the analysis. The majority of publications
      (30.8%) were conceptual papers or papers reporting clinical and rehabilitation
      studies (25.9%). One-third of the papers were published in 2008 and 2009.
      CONCLUSIONS: The ICF contributed to the development of research on functioning
      and on disability in clinical, rehabilitation as well as in several other
      contexts, such as disability eligibility and employment. Diffusion of ICF
      research and use in a great variety of fields and scientific journals is a proof
      that a cultural change and a new conceptualisation of functioning and disability
      is happening.

PMID- 21073362
TI  - Preventing heart failure and improving survival.

PMID- 21073364
TI  - Aldosterone antagonists--last man standing?

PMID- 21073366
TI  - An analysis of the diaminopyrimidine patent estates describing spleen tyrosine
      kinase inhibitors by Rigel and Portola.
AB  - IMPORTANCE OF THE FIELD: Discovery of small molecule inhibitors for treatment of
      rheumatoid arthritis is a major ongoing effort within the pharmaceutical
      industry. Spleen tyrosine kinase (SYK) is one of the leading small molecular
      targets with regard to clinical developments due to the efforts of Rigel and
      Portola. AREAS COVERED IN THIS REVIEW: Diaminopyrimidines are one of the most
      prominent structural elements incorporated into the design of kinase inhibitors.
      This review provides an extensive overview of the patent estates for the leading
      discovery programs at Portola and Rigel on diaminopyrimidines and how their
      patent estates are in relationship with the competition and prior art. WHAT THE
      READER WILL GAIN: An overview of the patent landscape for diaminopyrimidines. In
      addition, the reader will be updated on what modifications in these scaffolds
      lead to very potent SYK inhibitors as judged by the applications. Finally, the
      authors will provide their best guess on what the structure is of Portola's
      recently announced clinical candidate. TAKE HOME MESSAGE: The Rigel and the
      Portola research organizations have filed a series of patent applications on
      diaminopyrimidines as inhibitors of SYK. The scope of these applications is broad
      in a crowded chemical space. These applications contain very broad claims and the
      future will tell how much of the generic space claimed will be allowed in granted
      patents.

PMID- 21073367
TI  - Mentally disordered offenders' daily occupations after one year of forensic care.
AB  - Persons detained as mentally disordered offenders need support for transition
      from care to community life. Few systematic studies have been completed on the
      outcomes of standard forensic care. The aim was to investigate the target group's
      life conditions and daily occupations one year after care. In a follow-up design
      occupational performance (OP) and social participation (SP) were investigated at
      two time points. After informed consent 36 consecutively recruited participants
      reported OP using the Capability to Perform Daily Occupations, Self-Efficacy
      Scale, Importance scale, and Allen Cognitive Level Screen. SP was measured with
      the Manchester Short Assessment of Quality of Life, and Interview Schedule for
      Social Interaction. After one year 24 participants were still incarcerated, 11
      were conditionally released, and one participant was discharged. The group were
      generally more satisfied and engaged in daily occupations than at admission. The
      study's attrition rate, 51%, is discussed. The conclusion and the clinical
      implications indicate that the target group need early, goal directed
      interventions in OP and SP for alterations in daily occupations. Furthermore, to
      increase the knowledge base concerning mentally disordered offenders, studies
      with research designs that have the potential to uncover changes in daily
      occupation and other measures for this target group are necessary.

PMID- 21073368
TI  - Reciprocal capacity building for collaborative disability research between
      disabled people's organizations, communities and higher education institutions.
AB  - This paper focuses on the reciprocal capacity building that occurred through
      collaborative research between occupational therapy departments from six higher
      education institutions in South Africa, community-based organizations and a
      disabled people's organization on disabled youth and their livelihoods. The
      authors aimed to identify principles for collaboration and capacity building from
      the pilot phase and first phase of the main study. Occupational therapy
      departments place students in communities for service learning experience, but
      little collaboration with disabled people's organizations and communities in
      research processes occurs that could enrich such partnerships and inform relevant
      curriculum development. Secondary data from different sources including a
      transcript of a focus-group interview with the researchers in the pilot phase,
      workshop reports, and transcripts of free-writing exercises done by researchers
      were analysed thematically, both inductively and deductively. Two themes are
      explored: first, reciprocal building of organizational capacity and, second,
      generating collaborative relationships. The principles that were identified are
      integral to the strengths and challenges faced when multiple organizations work
      together over a wide geographical area on a complex research topic that also
      builds capacity reciprocally.

PMID- 21073369
TI  - Work-related self-efficacy of occupational therapists in mental health.
AB  - AIM: Changes in the mental health field have created new job expectations of
      occupational therapists (OTs). The present research investigated differences in
      general self-efficacy (GSE) and work-related self-efficacy (WRSE) between
      occupational therapists (OTs) working in psychiatric hospitals and OTs working in
      community-based mental health services. METHOD: Thirty-four OTs working in
      psychiatric hospitals and 30 OTs working in community-based settings (n = 60)
      completed the General Self Efficacy Scale (GSE) and the WRSE in Mental Health
      Occupational Therapy Scale (WSMOT). RESULTS: The two groups showed no differences
      in total WRSE score. Both evinced high self-efficacy in direct intervention
      activities, and low self-efficacy in managing and counseling. CONCLUSION: Results
      enlighten an overall high WRSE, which indicates successful adaptation of OTs to
      changing roles and tasks in mental health, similar to studies in other countries.
      However, it reveals discrepancies between job demands and self-efficacy of OTs
      that should be addressed at educational and managerial levels.

PMID- 21073370
TI  - Computer analysis of 24-h esophageal impedance signals.
AB  - OBJECTIVE: To assess the accuracy of newly developed software for detection of
      gastro-esophageal reflux episodes in ambulatory 24-h impedance tracings. MATERIAL
      AND METHODS. 24-h esophageal impedance recordings obtained from 60 consecutive
      patients with reflux symptoms were used in this study. The impedance tracings of
      the first 10 consecutive patients were analyzed manually by three investigators.
      Liquid-containing reflux episodes and their proximal extent were scored. A
      consensus between the three investigators was used as a gold standard. Computer
      analysis using dedicated software was performed, and the results were compared
      with the results of the consensus agreement. In addition, in order to assess the
      accuracy of symptom association analysis 24-h impedance tracings of all 60
      patients were analyzed both manually by one investigator and using computer
      software. The number of reflux episodes and the results of symptom association
      analysis obtained by the human and computer analysis software were compared.
      RESULTS: The consensus meeting resulted in a total of 625 reflux episodes. The
      mean sensitivity and the percentage of true-positives of analysis by individual
      investigators was 89+/-1% and 94+/-1%, respectively. Automated analysis had a
      sensitivity of 73+/-4% and a proportion of true-positive reflux episodes of 62+/
      8%. Symptom association analysis performed by the computer and a human observer
      showed concordant results in 83% of the patients. CONCLUSIONS: Although not as
      good as manual analysis by experts, computer analysis can be a helpful tool to
      identify reflux episodes and to assess the relationship between reflux episodes
      and symptoms.

PMID- 21073371
TI  - Coumarin-induced intramural hematoma of the duodenum: case report and review of
      the literature.
AB  - OBJECTIVE: Intramural hematoma of the small intestine is a complication of
      anticoagulant treatment with an estimated incidence of 1 case per 2500
      anticoagulated patients per year. Patients may present with signs of small bowel
      obstruction or, in case of a ruptured hematoma, with upper gastrointestinal tract
      hemorrhage and hypovolemic shock. MATERIAL AND METHODS: Case report and review of
      the literature. RESULTS: We present a case of a 73-year-old male who was referred
      for a protruding mass in the duodenum and subsequently developed hematemesis and
      melena caused by a ruptured hematoma of the duodenal wall. CONCLUSIONS: Although
      intramural hematoma of the duodenum is a rare complication of anticoagulant
      therapy, early diagnosis with subsequent correction of coagulation parameters is
      of vital importance.

PMID- 21073372
TI  - Comparison of the efficacy of irsogladine maleate and famotidine for the healing
      of gastric ulcers after Helicobacter pylori eradication therapy: a randomized,
      controlled, prospective study.
AB  - OBJECTIVE: Helicobacter pylori eradication therapy alone cannot heal gastric
      ulcers in Japanese patients. Irsogladine has previously been shown to accelerate
      the healing of gastric ulcers after H. pylori eradication therapy. And we
      previously reported that histamine H(2) receptor antagonists inhibit gastric
      ulcer relapse after H. pylori eradication therapy. We therefore compared the
      efficacy of irsogladine with famotidine as appropriate treatments for ulcers
      after eradication therapy. METHODS: Gastric ulcer patients with H. pylori
      infection (n = 119) were randomized to treatment with irsogladine 4 mg/day (n =
      60) or famotidine 40 mg/day (n = 59) following 1-week H. pylori eradication
      therapy. After treatment, assessments of gastric ulcer healing were performed.
      RESULTS: The ulcer healing rates in patients receiving irsogladine and famotidine
      were 85.2% (46/54) and 79.6% (43/54), respectively, and were not significantly
      different (p = 0.4484). In the famotidine group, the healing rate was
      significantly lower in patients who drink alcohol than in those who do not (60.0%
      vs. 91.2%; p = 0.0119). However, in the irsogladine group the healing rate did
      not differ between patients who drink alcohol and those who do not. Furthermore,
      the healing rate in smokers was significantly higher in the irsogladine group
      (88.0%) than in the famotidine group (59.1%) (p = 0.0233). CONCLUSIONS:
      Irsogladine and famotidine are both acceptable in treatment after H. pylori
      eradication therapy in gastric ulcer patients. Findings also suggest that
      irsogladine is more beneficial than famotidine in patients who drink alcohol and
      smoke.

PMID- 21073373
TI  - Serum fatty acid profile in subjects with irritable bowel syndrome.
AB  - OBJECTIVE: Irritable bowel syndrome (IBS) is a fluctuating disorder of the
      gastrointestinal tract, characterized by abdominal pain and change in bowel
      habit. We wanted to investigate subjects with IBS for signs of disturbed
      intestinal absorption of fatty acids, as reflected in serum composition. MATERIAL
      AND METHODS: Serum samples were obtained from 32 adults with IBS, and from 59
      controls. Serum fatty acids were analyzed by capillary gas-liquid chromatography.
      RESULTS: Especially the proportions of arachidonic acid (20:4 n-6) and the long
      chain polyunsaturated fatty acids of the n-3 family docosapentaenoic acid (22:5 n
      3) and docosahexaenoic acid (22:6 n-3) were decreased in subjects with IBS. The
      proportions of unsaturated and monounsaturated fatty acids were generally
      increased in IBS compared to controls. CONCLUSIONS: Although organic disease has
      been ruled out in patients with IBS, they presented signs of inadequate supply of
      long-chain fatty acids. Supplementation with n-3 fatty acids may be implicated.

PMID- 21073363
TI  - Eplerenone in patients with systolic heart failure and mild symptoms.
AB  - BACKGROUND: Mineralocorticoid antagonists improve survival among patients with
      chronic, severe systolic heart failure and heart failure after myocardial
      infarction. We evaluated the effects of eplerenone in patients with chronic
      systolic heart failure and mild symptoms. METHODS: In this randomized, double
      blind trial, we randomly assigned 2737 patients with New York Heart Association
      class II heart failure and an ejection fraction of no more than 35% to receive
      eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy.
      The primary outcome was a composite of death from cardiovascular causes or
      hospitalization for heart failure. RESULTS: The trial was stopped prematurely,
      according to prespecified rules, after a median follow-up period of 21 months.
      The primary outcome occurred in 18.3% of patients in the eplerenone group as
      compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence
      interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving
      eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI,
      0.62 to 0.93; P=0.008); 10.8% and 13.5%, respectively, died of cardiovascular
      causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Hospitalizations for
      heart failure and for any cause were also reduced with eplerenone. A serum
      potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the
      eplerenone group and 7.2% of those in the placebo group (P<0.001). CONCLUSIONS:
      Eplerenone, as compared with placebo, reduced both the risk of death and the risk
      of hospitalization among patients with systolic heart failure and mild symptoms.
      (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.).

PMID- 21073374
TI  - The prevalence of anemia and iron deficiency in IBD outpatients in Scandinavia.
AB  - OBJECTIVE: To evaluate the prevalence of anemia and iron deficiency (ID) among
      patients with inflammatory bowel disease (IBD) in the Scandinavian countries.
      MATERIAL AND METHODS: A cross-sectional study including 429 IBD patients from six
      centers in Denmark, Norway and Sweden. Patients were screened for anemia and ID.
      Each center included ~5% of their IBD cohort. Patients were consecutively seen in
      the outpatient clinic, regardless of disease activity and whether the visits were
      scheduled or not. RESULTS: The overall prevalence of anemia was 19% (95% CI: 16
      23%). The prevalence was higher among patients with Crohn's disease than among
      patients with ulcerative colitis (p = 0.01). The etiology of anemia was as
      follows: iron deficiency anemia (20%), anemia of chronic disease (12%), and both
      conditions (68%). Less than 5% had folate acid or vitamin B12 deficiency. ID was
      found in 35% (CI: 31-40%) of the patients. CONCLUSIONS: Anemia was present in
      every fifth IBD patient and ID in every third IBD patient.

PMID- 21073375
TI  - Gastric phenotype in children with Helicobacter pylori infection undergoing upper
      endoscopy.
AB  - INTRODUCTION: Helicobacter pylori is a definite risk factor for the development
      of gastric cancer, especially in the context of corpus-predominant gastritis. The
      infection is usually acquired in early childhood, implying lifelong exposure to
      this carcinogen if untreated. Our objective was to analyze the prevalence of H.
      pylori induced corpus-predominant gastritis in children. MATERIAL AND METHODS: We
      analyzed the results of 265 esophagogastroduodenoscopies (EGD) in children
      performed between February 2006 and August 2008; 34 endoscopies were excluded (24
      with follow-up investigations, 5 with incomplete data, 5 adults). H. pylori
      gastritis was defined by the presence of H. pylori in histology or by a positive
      rapid urease test. Grade of inflammation was rated according to the updated
      Sydney Scoring System. Gastritis was classified as corpus-predominant when the
      degree of chronic inflammation was higher in the corpus than in the antrum and
      vice versa for antrum-predominant gastritis. RESULTS: Two hundred thirty-one
      patients (128 female; mean age +/- SEM: 10.5 +/- 3.5 years) were analyzed. Eighty
      four (36%) were H. pylori positive, 147 (64%) patients were negative for H.
      pylori. In H. pylori positive patients, 39 (46%) patients had pangastritis (one
      patient with mucosal atrophy, which is regarded as precancerous lesion), 42 (50%)
      had antrum-predominant gastritis and 3 (4%) had corpus-predominant gastritis. One
      female patient (15.6 years old) with severe (grade 3) pangastritis had focal
      mucosal atrophy in both antrum and corpus, but no patient had intestinal
      metaplasia. CONCLUSIONS: Corpus-predominant gastritis develops in H. pylori
      infected children, while mucosal atrophy and intestinal metaplasia develop later
      in the course of the infection.

PMID- 21073378
TI  - On back order.

PMID- 21073365
TI  - Cardiac-resynchronization therapy for mild-to-moderate heart failure.
AB  - BACKGROUND: Cardiac-resynchronization therapy (CRT) benefits patients with left
      ventricular systolic dysfunction and a wide QRS complex. Most of these patients
      are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated
      whether adding CRT to an ICD and optimal medical therapy might reduce mortality
      and morbidity among such patients. METHODS: We randomly assigned patients with
      New York Heart Association (NYHA) class II or III heart failure, a left
      ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of
      120 msec or more or a paced QRS duration of 200 msec or more to receive either an
      ICD alone or an ICD plus CRT. The primary outcome was death from any cause or
      hospitalization for heart failure. RESULTS: We followed 1798 patients for a mean
      of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the
      ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in
      the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In
      the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group
      (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were
      hospitalized for heart failure, as compared with 236 in the ICD group (hazard
      ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device
      implantation, adverse events had occurred in 124 patients in the ICD-CRT group,
      as compared with 58 in the ICD group (P<0.001). CONCLUSIONS: Among patients with
      NYHA class II or III heart failure, a wide QRS complex, and left ventricular
      systolic dysfunction, the addition of CRT to an ICD reduced rates of death and
      hospitalization for heart failure. This improvement was accompanied by more
      adverse events. (Funded by the Canadian Institutes of Health Research and
      Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).

PMID- 21073376
TI  - Liver transplantation for cholangiocarcinoma: selection is essential for
      acceptable results.
AB  - BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is considered a contraindication
      for liver transplantation by most liver transplant centers. The aim of this study
      has been to report our results as well as to explore factors that influence
      patient survival after liver transplantation for CCA. PATIENTS: All transplant
      patients with CCA in Norway, Sweden and Finland during 1984-2005 were included (n
      = 53). Thirty-three patients (62%) had intrahepatic CCA. Twenty-one patients
      (40%) had a more advanced tumor (>TNM stage 2). Thirty-four of the 53 recipients
      (64%) had primary sclerosing cholangitis (PSC). RESULTS: Patients with TNM stage
      <= 2 transplanted after 1995 had a 5-year survival rate of 48%. The overall 5
      year patient survival rate was 25%. There was no difference in survival between
      patients with extrahepatic and intrahepatic CCA. The 5-year survival rate among
      patients with TNM stage <= 2 was 36%. Patients with TNM stage >2 had a 10% 5-year
      survival rate; the difference was significant at p < 0.01. Patients transplanted
      after 1995 had a significantly better 5-year survival rate than pre-1995 patients
      (38% vs. 0%, p < 0.01). Patients transplanted after 1995 with TNM <= 2 and CA 19
      9 <= 100 had the 5-year survival of 58%. CONCLUSION: By selecting CCA patients
      with TNM stage <= 2 and a CA 19-9 <= 100 a reasonable 5-year survival rate is
      possible. We think that CCA in selected cases can be an acceptable indication for
      liver transplantation.

PMID- 21073379
TI  - Comments on strategies to increase diversity in the profession.

PMID- 21073380
TI  - What is your diagnosis? Musculoskeletal neoplasia.

PMID- 21073381
TI  - What is your diagnosis? Traumatic pleuropericardial rupture.

PMID- 21073382
TI  - Pathology in practice. Poxvirus infection.

PMID- 21073383
TI  - ECG of the Month. Accessory atrioventricular pathway-mediated tachycardia.

PMID- 21073384
TI  - Animal behavior case of the month. Status aggression.

PMID- 21073385
TI  - What is the evidence? Intervertebral disk disease.

PMID- 21073386
TI  - Effects of acepromazine, hydromorphone, or an acepromazine-hydromorphone
      combination on the degree of sedation in clinically normal dogs.
AB  - OBJECTIVE: To determine the effects of IM administration of acepromazine,
      hydromorphone, or the acepromazine-hydromorphone combination on degree of
      sedation in clinically normal dogs and to compare 2 sedation scoring techniques.
      DESIGN: Prospective, randomized, blinded, controlled trial. Animals-46 random
      source dogs. PROCEDURES: Dogs were assigned to receive IM administrations of
      acepromazine (0.05 mg/kg [0.023 mg/lb]; [DOSAGE ERROR CORRECTED] n = 12),
      hydromorphone (0.1 mg/kg [0.045 mg/lb]; 11), acepromazine-hydromorphone (0.5
      mg/kg and 0.1 mg/kg, respectively; 12), or saline (0.9% NaCI) solution (0.05
      mL/kg [0.023 mL/lb]; 11). Sedation scores were determined at 0 (time of
      administration), 15, 30, 45, and 60 minutes by use of a subjective scoring system
      (SSS) and a simple numeric rating scale (NRS). RESULTS: Acepromazine caused
      significantly greater sedation than did saline solution at 15, 30, 45, and 60
      minutes. Acepromazine-hydromorphone caused significantly greater sedation than
      did saline solution at 15, 30, 45, and 60 minutes and than did hydromorphone
      alone at 30 minutes. Hydromorphone alone did not cause significantly greater
      sedation than did saline solution. All treatments, including saline solution,
      caused significantly greater sedation at 45 and 60 minutes, compared with
      sedation at time 0. There was a significant correlation (r(2) = 0.72) between
      scores obtained with the SSS and NRS, but the NRS was less sensitive for
      detecting clinically important sedation. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of acepromazine or acepromazine-hydromorphone caused sedation in
      clinically normal dogs, whereas administration of hydromorphone alone did not.
      The NRS was a less-reliable measure of sedation.

PMID- 21073387
TI  - Magnetic resonance imaging features and clinical signs associated with
      presumptive and confirmed progressive myelomalacia in dogs: 12 cases (1997-2008).
AB  - OBJECTIVE: To characterize clinical signs and findings from magnetic resonance
      imaging (MRI) and CSF analysis for dogs with progressive myelomalacia (PM)
      diagnosed on the basis of clinical and histologic features. DESIGN: Retrospective
      case series. ANIMALS: 5 dogs with confirmed PM and 7 with presumptive PM
      evaluated from 1997 through 2008. PROCEDURES: Medical records of study dogs were
      reviewed, and clinical signs and MRI and CSF findings were evaluated. A clinical
      diagnosis of PM was made on the basis of detection of disk-associated spinal cord
      compression via MRI and progression of clinical signs from initial paraparesis or
      paraplegia to thoracic limb lower motor neuron paresis to tetraplegia associated
      with cranial migration of the extent of cutaneous trunci reflex extinction and
      analgesia, terminating in death due to respiratory paralysis. RESULTS: All dogs
      were paraplegic and had signs of lower motor neuron lesions. As revealed by MRI
      of the vertebral column, the length of abnormal signal intensity was more than 6
      fold, compared with the body length of L2. In some dogs, these abnormal MRI
      findings were observed before PM was clinically diagnosed. The CSF examination
      revealed hemorrhagic xanthochromia. CONCLUSIONS AND CLINICAL RELEVANCE: A
      hyperintense region of the spinal cord > 6 times the length of L2 on T2-weighted
      imaging might be a characteristic MRI finding of PM. In some dogs, such MRI
      findings were observed before PM was clinically diagnosed. Progressive
      myelomalacia may thus be diagnosable at the early stage through MRI and CSF
      examination before signs of PM develop.

PMID- 21073388
TI  - Development, application, and validation of a survey for infectious disease
      control practices at equine boarding facilities.
AB  - OBJECTIVE: To develop a questionnaire for self-assessment of biosecurity
      practices at equine boarding facilities and to evaluate infectious disease
      control practices in these facilities in Colorado. DESIGN: Cross-sectional study.
      SAMPLE POPULATION: 64 equine boarding facilities in Colorado. PROCEDURES: Survey
      questions were rated according to importance for prevention and containment of
      equine infectious diseases. Point values (range, 0 to 20) were assigned for
      possible responses, with greater values given for optimal infection control
      methods. Questionnaires were mailed to equine boarding facilities in Colorado
      advertised on the World Wide Web. Survey responses were compared with assessments
      made by a member of the research team during visits to 30 randomly selected
      facilities. Agreement among results was analyzed via a kappa test and rated as
      poor, fair, moderate, substantial, or nearly perfect. RESULTS: Survey responses
      were received for 64 of 163 (39%) equine boarding facilities. Scores ranged from
      106 to 402 points (maximum possible score, 418). Most facilities received better
      scores for movement and housing of equids than for other sections of the survey.
      Respondents at 24 of 48 (50%) facilities that routinely received new equids
      reported isolation of new arrivals. Agreement between self-assessment by survey
      respondents and evaluation by a member of the research team was determined to be
      fair to substantial. CONCLUSIONS AND CLINICAL RELEVANCE: Most equine boarding
      facilities have opportunities to improve measures for prevention or containment
      of contagious diseases (eg, isolation of newly arrived equids and use of written
      health management protocols). Most self-assessments of infection control
      practices were accurate.

PMID- 21073389
TI  - Wooden, metallic, hair, bone, and plant foreign bodies in horses: 37 cases (1990
      2005).
AB  - OBJECTIVE: To characterize features of diagnosis, treatment, and outcome in
      horses with foreign bodies, exclusive of enteric, inhaled, and foot-penetrating
      foreign bodies. DESIGN: Retrospective case series. ANIMALS: 37 horses with
      foreign bodies. PROCEDURES: The incidence of equine foreign bodies from 1990
      through 2005 was determined by review of data from veterinary schools
      participating in the Veterinary Medical Database (VMDB). Medical records of
      horses with foreign bodies at Purdue University were reviewed, and the following
      information was retrieved: clinical history; signalment; results of physical,
      radiographic, and ultrasonographic examinations; results of microbial culture of
      the draining tract or foreign body material; surgical findings; antimicrobial and
      anti-inflammatory treatments; and complications of the surgical procedure. Long
      term follow-up information was obtained from owners or referring veterinarians.
      RESULTS: The incidence of foreign bodies in horses with records in the VMDB was
      1730/10,000 horse admissions. A preoperative diagnosis of foreign bodies was
      confirmed via ultrasonography in most horses examined (15/17 horses) and with
      plain film radiography in a quarter of horses examined (7/24 horses). Wood
      foreign bodies were the most common (59%; 22/37), followed by metal (24%; 9/37),
      hair (8%; 3/37), nonsequestrum bone (5%; 2/37), and plant material (3%; 1/37).
      Postoperative complications associated with the foreign body were more likely to
      develop with wood foreign bodies (3/22) than with other types of foreign bodies
      (1/15). CONCLUSIONS AND CLINICAL RELEVANCE: Wood was the most common penetrating
      foreign body in the horses in our study and was the type associated with the
      highest incidence of complications. Ultrasonography was more effective in
      locating foreign bodies than was radiography (plain and contrast) and should be
      performed in all horses with suspected foreign bodies.

PMID- 21073390
TI  - Meningitis, cranial neuritis, and radiculoneuritis associated with Borrelia
      burgdorferi infection in a horse.
AB  - CASE DESCRIPTION: A 12-year-old Thoroughbred was examined because of signs of
      depression, neck stiffness, and poor performance. CLINICAL FINDINGS: Physical
      examination revealed that the horse was dull, appeared depressed, was reluctant
      to raise its neck and head above a horizontal plane, and had a temperature of
      38.5 degrees C (101.3 degrees F). No radiographic or scintigraphic abnormalities
      of the neck were found; however, high plasma fibrinogen concentration and
      relative lymphopenia were identified and the horse was seropositive for
      antibodies against Borrelia burgdorferi. Analysis of CSF revealed neutrophilic
      inflammation, and results of a PCR assay of CSF for B burgdorferi DNA were
      positive. Immunologic testing revealed severe B-cell lymphopenia and a low serum
      IgM concentration consistent with common variable immunodeficiency. TREATMENT AND
      OUTCOME: The horse responded well to do*ycycline treatment (10 mg/kg [4.5 mg/lb],
      PO, q 12 h for 60 days) and returned to normal exercise. However, 60 days after
      treatment was discontinued, the horse again developed a stiff neck and rapidly
      progressive neurologic deficits, including severe ataxia and vestibular deficits.
      The horse's condition deteriorated rapidly despite IV oxytetracycline treatment,
      and the horse was euthanatized. Postmortem examination revealed leptomeningitis,
      lymphohistiocytic leptomeningeal vasculitis, cranial neuritis, and peripheral
      radiculoneuritis with Wallerian degeneration; findings were consistent with a
      diagnosis of neuroborreliosis. CLINICAL RELEVANCE: Nervous system infection with
      B burgdorferi should be considered in horses with evidence of meningitis and high
      or equivocal serum anti-B burgdorferi antibody titers. Evaluation of immune
      function is recommended in adult horses evaluated because of primary bacterial
      meningitis.

PMID- 21073391
TI  - Scapulohumeral joint luxation in alpacas: 10 cases (2003-2009).
AB  - OBJECTIVE: To describe the clinical findings, treatments, and outcome in alpacas
      treated for scapulohumeral joint luxation (SHJL). DESIGN: Retrospective case
      series. ANIMALS: 10 alpacas. PROCEDURES: Medical records of alpacas with SHJL
      that were treated at 2 referral hospitals were reviewed. History, signalment,
      physical examination results, radiographic findings, treatments, complications,
      and outcome were evaluated. RESULTS: Records for 8 male and 2 female alpacas with
      16 instances of SHJL were reviewed. Three male alpacas each had 2 recurrences of
      SHJL in the treated limb. The proportion of male alpacas treated for SHJL was
      significantly greater than the proportion of female alpacas treated for SHJL.
      Closed reduction was used in 2 female and 3 male alpacas; SHJL reccurred in the 3
      males. Stabilization by use of a lateral extracapsular tension band suture
      technique was performed successfully in 4 male alpacas; in another male alpaca,
      reluxation caused by self-inflicted trauma occurred postoperatively. In 2 male
      alpacas, arthrodesis was performed but residual lameness remained 1 year after
      surgery. CONCLUSIONS AND CLINICAL RELEVANCE: SHJL should be considered as a
      differential diagnosis in alpacas with thoracic limb lameness. Luxation may occur
      more frequently in males. A closed reduction technique may be used successfully
      to treat acute luxations. Extracapsular stabilization by use of the lateral
      extracapsular tension band suture technique was successful for treatment of
      recurrent SHJL and SHJL that could not be reduced via closed reduction.

PMID- 21073392
TI  - Presentation, response to lansoprazole therapy, and outcome of Zollinger-Ellison
      syndrome-like gastric acid hypersecretors.
AB  - OBJECTIVE: To evaluate the clinical characteristics, response to treatment and
      outcome of Zollinger?Ellison syndrome (ZES)-like gastric acid hypersecretors.
      METHODS: Over a 20-year period, patients with gastric acid hypersecretion in the
      absence of ZES were enrolled in an open label prospective trial evaluating the
      efficacy of lansoprazole. Following baseline evaluations, patients were treated
      with escalating doses of lansoprazole based on the results of gastric acid
      analysis. Following stabilization, patients were followed on a 6 monthly basis
      with interval history, physical examination, endoscopy with gastric biopsies,
      gastric acid analysis, and laboratory studies. RESULTS: The study group
      represented 21 patients (median age 47 years, 86% male, 91% Caucasian).
      Historically, complicated ulcer disease was frequent and symptoms had been
      present for a median of 10 years before study entry. All patients responded to
      lansoprazole (median dose 90 mg/day) with excellent control of gastric acid
      hypersecretion. Mucosal relapse was infrequent and no major complications
      developed while on therapy. CONCLUSIONS: ZES-like gastric acid hypersecretion
      presents similarly to the classic syndrome. Lansoprazole titrated to gastric acid
      output is effective in healing mucosal disease and preventing relapse.

PMID- 21073393
TI  - Monocyte chemoattractant protein-1 is related to metabolic syndrome and
      homocysteine in subjects without clinically significant atherosclerotic
      cardiovascular disease.
AB  - BACKGROUND: The features of the metabolic syndrome include glucose intolerance,
      hypertension, dyslipidemia, and central obesity, all of which are risk factors
      for diabetes and cardiovascular disease. Monocyte chemoattractant protein-1 (MCP
      1) and interleukin-8 (IL-8) play a key role in atherosclerosis. We examined the
      association between chemokines, such as MCP-1 and IL-8, and metabolic syndrome.
      METHODS: The present study was comprised of 54 men and 126 women. Subjects with
      cardiovascular disease such as myocardial infarction, TIA and cerebral infarction
      were excluded. RESULTS: MCP-1 was positively correlated with homeostasis model
      assessment of insulin resistance, homocysteine, and mean pulse wave velocity, but
      IL-8 was not. In multiple regression analysis, age, HOMA-IR and homocysteine were
      found to be an independent factor associated with MCP-1 adjusted by gender,
      waist, systolic blood pressure, triglyceride, HDL-cholesterol, and hs-CRP. After
      adjustment for age and gender, mean MCP-1 was higher in subjects with metabolic
      syndrome and in subject with high blood pressure among the individual components
      of the metabolic syndrome. CONCLUSION: MCP-1 was associated with a low-grade
      systemic inflammatory reaction which is often found in the metabolic syndrome.

PMID- 21073394
TI  - A thrombin generation assay may reduce the need for compression ultrasonography
      for the exclusion of deep venous thrombosis in the elderly.
AB  - INTRODUCTION: The exclusion of deep venous thrombosis (DVT) by pre-test
      probability (PTP) and D-dimer in the elderly is safe, but has a low specificity.
      There is increasing interest in the diagnostic role of thrombin generation in
      patients with thrombosis. We evaluated the value of thrombin generation in the
      exclusion of DVT, especially in elderly patients. MATERIAL AND METHODS: All
      thrombin generation parameters of the Endogenous Thrombin Potential assay were
      tested retrospectively in a cohort of 443 patients suspected for DVT. The
      performance of the assay was calculated as AUC of the ROC curve and association
      with DVT as odds ratio (OR). The lag time value was combined with results of PTP
      and Innovance D-dimer assay. RESULTS: All thrombin generation parameters had a
      low AUC. In the 4th age quartile, the corrected OR of lag time increased to 16
      and the AUC of lag time for the combination PTP < 2 and D-dimers >= 500 MUg/L was
      0.96 with a cut-off value of 23.0 sec. The exclusion of DVT in patients >= 75
      years (n = 30), based on this combination and lag time values <= 23.0 sec had a
      NPV of 100% and a specificity of 96.0% in this subgroup of patients and decreased
      the number needed to test from 10 to 1.1. CONCLUSION: Thrombin generation
      parameters alone are inappropriate for the exclusion of DVT. However, in the
      elderly, the current algorithm of exclusion of DVT may improve markedly by the
      addition of the lag time results of the ETP.

PMID- 21073395
TI  - Alteration of the pro-oxidant xanthine oxidase (XO) in the thalamus and occipital
      cortex of patients with schizophrenia.
AB  - OBJECTIVES: Mounting evidence shows that oxidative stress (OS) and the
      purine/adenosine system play a key role in the pathophysiology of schizophrenia.
      Lately, our group pointed out that not only antioxidants, but also the prooxidant
      system plays an important role in neuro-psychiatric disorders. Xanthine oxidase
      (XO) is an enzyme of special interest in this context, since it acts as a
      prooxidant, but its main product is a vastly important antioxidant, uric acid
      (UA). Furthermore, XO plays major part in the purine/adenosine metabolism, which
      has been hypothesised to play a role in schizophrenia as well. METHODS: We
      examined the activity of XO in the striato-cortico-limbic system of schizophrenic
      patients (SP) and controls using a commercially available activity assay.
      RESULTS: We found decreased activity of XO in the occipital cortex and thalamus
      of patients with psychosis. Furthermore, XO shows a significant positive
      correlation with chlorpromazine equivalents in the putamen and the temporal
      cortex. CONCLUSIONS: Nevertheless, our results might suggest a downregulation of
      cellular defence mechanisms in schizophrenia in several brain regions, which
      could account for neuronal alterations which have been described before. This
      demonstrates that more research is needed to fully understand the role of the
      complex enzyme XO in the pathophysiology of schizophrenia.

PMID- 21073396
TI  - Vitamin D supplementation for patients with chronic pain.

PMID- 21073397
TI  - Safety of home parenteral nutrition in patients with amyotrophic lateral
      sclerosis: a French national survey.
AB  - We carried out a retrospective multicentre study to assess the safety of home
      parenteral nutrition (HPN) in patients with ALS. We reviewed the case records of
      patients from French ALS centres treated with HPN by central venous catheter
      (CVC) using an implantable port between January 2005 and October 2009. Seventy
      three patients received HPN for a total of 11,908 catheter days. Twenty-seven
      patients experienced a total of 37 CVC related complications resulting in an
      incidence rate of 3.11 CVC complications/1000 catheter days, including 1.93
      septic complications and 1.09 mechanical complications/1000 catheter days.
      Metabolic complications were frequent but without serious consequences on
      mortality. The use of the catheter for intravenous therapies in addition to HPN
      was identified as a septicaemia's risk factor (relative risk (RR) = 2.54,
      confidence interval (CI) 1.56-4.14, p = 0.04). In conclusion, HPN is an
      alternative procedure to PEG in advanced ALS patients. The incidence of
      complications appears to be comparable to data from the literature on HPN in
      other diseases. A prospective study comparing HPN and radiologic inserted
      gastrostomy (RIG) would allow comparison of the relative risk-benefit and
      survival of these procedures. The relation of CVC and RIG placement timing and
      the complications' occurrence should also be investigated.

PMID- 21073398
TI  - The role of word familiarity in Spanish/English bilingual word recognition.
AB  - OBJECTIVE: This study examined the contribution of word familiarity to
      Spanish/English bilingual listeners' recognition of English and Spanish words.
      DESIGN: The study employed a counterbalanced design. Three lists of monosyllabic
      English and bisyllabic Spanish words (50 words per list per language) were
      presented in two blocks. For each block, word lists were presented in quiet and
      at +6 and 0 dB SNR. Listeners repeated each word in verbal and written forms. At
      the end of the experiment, they rated the familiarity of the test words on a
      seven-point scale. STUDY SAMPLE: Twenty English-dominant (ED) and 22 Spanish
      dominant (SD) normal-hearing adult listeners participated in the study. RESULTS:
      Most test words, English or Spanish, were familiar to the listeners. However, ED
      listeners were less familiar with Spanish than English words, whereas SD
      listeners were less familiar with English than Spanish words. Contribution of
      word familiarity to word recognition remained largely constant across listening
      conditions for both English and Spanish tests. CONCLUSIONS: Despite high
      familiarity of most test words, clinicians should be aware of the residual
      effects of familiarity on the English word test even after most unfamiliar words
      are removed, regardless of clients' language dominance.

PMID- 21073399
TI  - Biohydrogen production and bioprocess enhancement: a review.
AB  - This paper provides an overview of the recent advances and trends in research in
      the biological production of hydrogen (biohydrogen). Hydrogen from both fossil
      and renewable biomass resources is a sustainable source of energy that is not
      limited and of different applications. The most commonly used techniques of
      biohydrogen production, including direct biophotolysis, indirect biophotolysis,
      photo-fermentation and dark-fermentation, conventional or "modern" techniques are
      examined in this review. The main limitations inherent to biochemical reactions
      for hydrogen production and design are the constraints in reactor configuration
      which influence biohydrogen production, and these have been identified.
      Thereafter, physical pretreatments, modifications in the design of reactors, and
      biochemical and genetic manipulation techniques that are being developed to
      enhance the overall rates and yields of biohydrogen generation are revisited.

PMID- 21073400
TI  - Characterization of nano oxaliplatin prepared by novel Fat Employing
      Supercritical Nano System, the FESNS(r).
AB  - BACKGROUND: Oxaliplatin has long been used for the treatment of colorectal cancer
      via intra-venous infusion. In order to improve patient compliance, a solid dosage
      form for oral administration of oxaliplatin was prepared as nano-sized particles.
      METHOD: Nano oxaliplatin was prepared employing Fat Employing Supercritical Nano
      System (FESNS((r))) with Supercritical Fluid (SCF) apparatus by using myristyl
      alcohol as solvent. Morphology of nano oxaliplatin was examined by Scanning
      Electron Microscopy (SEM), and the particle size and zeta potential were
      confirmed with Dynamic Light Scattering (DLS). To characterize the nano
      oxaliplatin particles, solubility rate and in vitro efficacy study (MTS growth
      inhibition assay) were investigated compared to crude oxaliplatin as reference.
      RESULT: FESNS((r)) provided reproducible nano oxaliplatin with high manufacturing
      yield (> 95%). SEM images showed that the particle size distribution of nano
      oxaliplatin ranged between 20 and 400 nm with the medium particle sizes (d(50))
      of about 164 nm determined by DLS. Pertaining to the long-term stability, no
      recrystallization of the nano oxaliplatin was observed with negative zeta
      potential in the state of solution. Nano oxaliplatin was completely dissolved
      within a couple of minutes in pH 4.0 and pH 6.8 buffer solutions while crude
      oxaliplatin took a couple of hours to go into solution. In case of MTS growth
      inhibition assay, the average concentration required to inhibit 50% of cell
      growth (GI(50)) of nano oxaliplatin was decreased by about 45% in comparison to
      the crude oxaliplatin. CONCLUSION: These results lead us to conclude that nano
      oxaliplatin would have a great potential for the improvement of efficacy and
      toxicity in human colorectal cancer treatment compared to the crude oxaliplatin.

PMID- 21073401
TI  - Ultrasonic dispersion of nanoparticles for environmental, health and safety
      assessment--issues and recommendations.
AB  - Studies designed to investigate the environmental or biological interactions of
      nanoscale materials frequently rely on the use of ultrasound (sonication) to
      prepare test suspensions. However, the inconsistent application of ultrasonic
      treatment across laboratories, and the lack of process standardization can lead
      to significant variability in suspension characteristics. At present, there is
      widespread recognition that sonication must be applied judiciously and reported
      in a consistent manner that is quantifiable and reproducible; current reporting
      practices generally lack these attributes. The objectives of the present work
      were to: (i) Survey potential sonication effects that can alter the
      physicochemical or biological properties of dispersed nanomaterials (within the
      context of toxicity testing) and discuss methods to mitigate these effects, (ii)
      propose a method for standardizing the measurement of sonication power, and (iii)
      offer a set of reporting guidelines to facilitate the reproducibility of studies
      involving engineered nanoparticle suspensions obtained via sonication.

PMID- 21073402
TI  - Comparative study of the uniformity of coating thickness of pellets coated with a
      conventional Wurster chamber and a swirl generator-equipped Wurster chamber.
AB  - This study evaluated the performance of two bottom-spray coaters and the effect
      of pellet-size variability on coating uniformity. A conventional Wurster chamber
      was used for the first group of trials, and a Wurster chamber with a novel swirl
      flow generator design was used for the second. The results confirmed that when
      using a conventional Wurster coating chamber, pellets with a smaller diameter
      receive significantly less coating material compared to those with larger
      diameters. The swirl generator-equipped Wurster chamber achieved close to uniform
      coating thickness regardless of pellet size. The ratio (M(S)) of the mass of dye
      deposited in the coating layer to pellet surface area indicates that coating was
      much more evenly distributed using the swirl-flow coater. Coating thickness was
      also analyzed using SEM micrographs and the results were in close agreement with
      the M(S) factor values. Inter-particle coating mass variation was also lower in
      case of swirl-flow coater. The results of this study show that a swirl-flow
      coater is suitable for coating particles of variable size. They also showed an
      improvement in coating process yield when using the swirl-flow coater.

PMID- 21073403
TI  - Characteristics, healthcare utilization and costs of bipolar disorder type I
      patients with and without frequent psychiatric intervention in a Medicaid
      population.
AB  - OBJECTIVE: To compare characteristics, healthcare resource utilization and costs
      of Medicaid bipolar disorder (BPD) type I (BP-I) patients with and without
      frequent psychiatric intervention (FPI). METHODS: Adults with BP-I, >= 1
      prescription claim for a mood stabilizer/atypical antipsychotic and 24 months'
      continuous medical/prescription coverage were identified (MarketScan* Medicaid
      database). Patients with >= 2 clinically significant events (CSEs) during a 12
      month identification period had FPI. CSEs included emergency department (ED)
      visits or hospitalizations with a principal diagnosis of BPD, addition of a new
      medication to the first observed treatment regimen or >= 50% increase in BPD
      medication dose. Demographic and clinical characteristics were evaluated for the
      identification period, and healthcare utilization and costs for the 12-month
      follow-up. Multivariate generalized linear modeling and multivariate logistic
      regression, respectively, were used to evaluate the impact of FPI on all-cause
      and psychiatric-related costs and risk of psychiatric-related hospitalization and
      ED visit during follow-up. RESULTS: Of 5,527 BP-I patients, 53% had FPI. Relative
      to patients without FPI, those with FPI were younger and more likely to be
      female, had higher adjusted all-cause (+US$3,232, p < 0.001) and psychiatric
      related (+US$2,519, p < 0.001) costs and higher risk of hospitalization (adjusted
      odds ratio [OR] = 3.681, 95% confidence interval [CI] = 2.85-4.75) and ED visit
      (OR = 3.094, 95% CI = 2.55-3.76). LIMITATIONS: Analysis used a convenience sample
      of Medicaid enrollees in several geographically dispersed states, limiting
      generalizability. Analyses of administrative claims data depend on accurate
      diagnoses and data entry. CONCLUSION: BP-I patients with FPI incurred
      significantly higher healthcare resource utilization and costs during the follow
      up period than those without FPI.

PMID- 21073404
TI  - Sex and ethnic differences in the waist circumference of 5-year-old children:
      findings from the Millennium Cohort Study.
AB  - We examined sex and ethnic differences in central fatness, as assessed by waist
      circumference measurements, in 13 590 Millennium Cohort Study 5-year-olds.
      Measurements were expressed as z-scores based on reference data from the British
      Standards Institute. The cohort, especially girls, had larger waist circumference
      measurements than the reference population. Black children had larger waist, and
      children from other minority ethnic groups had smaller waist than White children.
      Girls, and Black children, in the United Kingdom are at particular risk for
      central fatness. Further research is needed to clarify ethnic and other
      influences on fat distribution, and the health outcomes associated with central
      fatness.

PMID- 21073405
TI  - Kava: a comprehensive review of efficacy, safety, and psychopharmacology.
AB  - OVERVIEW: Kava (Piper methysticum) is a South Pacific psychotropic plant medicine
      that has anxiolytic activity. This effect is achieved from modulation of GABA
      activity via alteration of lipid membrane structure and sodium channel function,
      monoamine oxidase B inhibition, and noradrenaline and dopamine re-uptake
      inhibition. Kava is available over the counter in jurisdictions such as the USA,
      Australia and New Zealand. Due to this, a review of efficacy, safety and clinical
      recommendations is advised. OBJECTIVE: To conduct a comprehensive review of kava,
      in respect to efficacy, psychopharmacology, and safety, and to provide clinical
      recommendations for use in psychiatry to treat generalized anxiety disorder
      (GAD). METHODS: A review was conducted using the electronic databases MEDLINE,
      CINAHL, PsycINFO and the Cochrane Library during mid 2010 of search terms
      relating to kava and GAD. A subsequent forward search was conducted of key papers
      using Web of Science cited reference search. RESULTS: The current weight of
      evidence supports the use of kava in treatment of anxiety with a significant
      result occurring in four out of six studies reviewed (mean Cohen's d = 1.1).
      Safety issues should however be considered. Use of traditional water soluble
      extracts of the rhizome (root) of appropriate kava cultivars is advised, in
      addition to avoidance of use with alcohol and caution with other psychotropic
      medications. Avoidance of high doses if driving or operating heavy machinery
      should be mandatory. For regular users routine liver function tests are advised.
      CONCLUSIONS: While current evidence supports kava for generalized anxiety, more
      studies are required to assess comparative efficacy and safety (on the liver,
      cognition, driving, and sexual effects) versus established pharmaceutical
      comparators.

PMID- 21073406
TI  - Can we predict the age of menopause transition?

PMID- 21073407
TI  - Eu-estrogenemia and contemporary knowledge versus Rossouw's cohort and
      recommendations for HRT.

PMID- 21073411
TI  - Smoking correlates among Hispanic and non-Hispanic white adolescents in the US
      southwest.
AB  - We examined smoking correlates among Hispanic and white students in 6-12th grades
      in small communities in three states in the southwestern United States. Data were
      collected in 2002 from 8,479 participants, who completed surveys measuring a wide
      range of potential smoking correlates from individual, family, and peer domains.
      Logistic regression analyses showed that peer factors were the most robust
      correlates across both ethnicities and grade groups. An unexpected finding was
      the posited protective effect of male gender for older white students.
      Limitations and implications for prevention are discussed. This work was
      supported by the National Institute on Drug Abuse.

PMID- 21073412
TI  - Addiction research ethics and the Belmont principles: do drug users have a
      different moral voice?
AB  - This study used semi-structured interviews and content analysis to examine moral
      principles that street drug users apply to three hypothetical addiction research
      ethical dilemmas. Participants (n = 90) were ethnically diverse, economically
      disadvantaged drug users recruited in New York City in 2009 . Participants
      applied a wide range of contextually sensitive moral precepts, including respect,
      beneficence, justice, relationality, professional obligations, rules, and
      pragmatic self-interest. Limitations and implications for future research and the
      responsible conduct of addiction research are discussed.

PMID- 21073413
TI  - Toxicity and hemostatic potential of poly [beta-(1, 4)-2-amino-2-deoxy-D
      glucosamine] based hemostatic material on albino rabbits.
AB  - The present study was designed to evaluate the hemostatic potential of poly [beta
      (1, 4)-2-amino-2-deoxy-D-glucosamine]-based hemostatic dressing material on
      albino rabbits. In vitro cytotoxicity study of poly [beta-(1, 4)-2-amino-2-deoxy
      D-glucosamine]-based hemostatic dressing samples was carried out with L929 cells,
      and the cytotoxic potential was evaluated at the end of 24 h. The skin irritation
      was carried out in albino rabbits. Extract of the material was applied topically
      and irritation response was evaluated up to 72 h. The hemostatic study was
      initiated in rabbits after general anesthesia with a mixture of ketamine and
      xylazine. Using a sharp surgical blade, a 1.0 cm longitudinal incision was made
      on the right (test) and left (control) marginal ear arteries. Through the
      resultant jet spray of blood, the right 1.0 cm long wound was immediately covered
      with a 2 * 2 cm(2) piece of test material (poly [beta-(1,4)-2-amino-2-deoxy-D
      glucosamine] of known weight (w1). Similarly the left wound (1.0 cm length) was
      covered with commercially-available bandage (control) of known weight (w2).
      Direct pressure was applied for 2 min and then the samples were removed and
      weighed immediately (w3 for test and w4 for control) after hemostasis. Blood loss
      (w3-w1 for the Test and w4-w2 for control) was calculated from the materials
      weight before and after absorbing blood. The result of the study indicated that
      the indigenously developed material has local biological activity in the form of
      hemostatic action and, together with its ability to activate macrophages,
      resulted in wound healing applications. Hence, the present study concluded that
      the poly [beta-(1,4)-2-amino-2-deoxy-D glucosamine]-based hemostatic dressing
      material is non-toxic, non-skin irritant, and has better hemostatic potential
      than a commercially available material with enhanced hemostatic capabilities for
      various wound dressing.

PMID- 21073414
TI  - Renalase, a new secretory enzyme responsible for selective degradation of
      catecholamines: achievements and unsolved problems.
AB  - Renalase is a recently discovered secretory enzyme responsible for selective
      degradation of blood catecholamines. The review summarizes literature data on
      expression of this enzyme and on its structure and functions. Special attention
      is paid to unsolved and questionable problems including: 1) prediction of the
      presence of FAD in the protein structure based on amino acid sequence similarity
      of renalase with known FAD-dependent enzymes; 2) identity of plasma and urinary
      renalase; 3) mechanism underlying conversion of inactive renalase into the active
      form.

PMID- 21073415
TI  - DNA polymerases and carcinogenesis.
AB  - There are many various chromosomal and gene mutations in human cancer cells. The
      total mutation rate in normal human cells is 2.10(-7) mutations/gene/division.
      From 6 to 12 carcinogenic mutations can arise by the end of the life, and these
      can affect the structure of ~150 protooncogenes and genes encoding suppressors of
      tumor growth. However, this does not explain the tens and hundreds of thousands
      of mutations detectable in cancer cells. Mutation is any change of nucleotide
      sequence in cellular DNA. Gene mutations are mainly consequences of errors of DNA
      polymerases, especially of their specialized fraction (inaccurate DNA polymerases
      beta, zeta, eta, theta, iota, kappa, lambda, u, sigma, nu, Rev1, and terminal
      deoxynucleotidyl transferase, and only polymerases theta and sigma manifest a
      slight 3'-exonuclease activity) and also consequences of a decrease in the rate
      of repair of these errors. Inaccurate specialized human polymerases are able to
      synthesize DNA opposite lesions in the DNA template, but their accuracy is
      especially low during synthesis on undamaged DNA. In the present review
      fundamental features of such polymerases are considered. DNA synthesis stops in
      the area of its lesion, but this block is overcome due to activities of
      inaccurate specialized DNA polymerases. After the lesion is bypassed, DNA
      synthesis is switched to accurate polymerases alpha, delta, epsilon, or gamma.
      Mechanisms of direct and reverse switches of DNA polymerases as well as their
      modifications during carcinogenesis are discussed.

PMID- 21073416
TI  - Biochemical mechanisms of suppression of RNA interference by plant viruses.
AB  - RNA interference (RNAi) plays an important biological role in regulation of gene
      expression of eukaryotes. In addition, RNAi was shown to be an adaptive
      protective molecular immune mechanism against viral diseases. Antiviral RNAi
      initiates from generation of short interfering RNAs used in the subsequent
      recognition and degradation of the viral RNA molecules. As a response to
      protective reaction of plants, most of the viruses encode specific proteins able
      to counteract RNAi. This process is known as RNAi suppression. Viral suppressors
      act on various stages of RNAi and have biochemical properties that enable viruses
      to effectively counteract the protective system of plants. Modern molecular and
      biochemical investigations of a number of viral suppressors have significantly
      expanded our understanding of the complexity of the nature of RNAi suppression as
      well as mechanisms of interaction between viruses and plants.

PMID- 21073417
TI  - Investigation of mechanism of p38 MAPK activation in renal epithelial cell from
      distal tubules triggered by cardiotonic steroids.
AB  - Ouabain and other cardiotonic steroids (CTS) kill renal epithelial cells from
      distal tubules (C7-MDCK) via interaction with Na,K-ATPase but independently of
      inhibition of Na,K-ATPase-mediated ion fluxes. Recently, we demonstrated that
      modest intracellular acidification and inhibition of p38 MAPK suppress death of
      C7-MDCK cells triggered by ouabain. In the present study we investigate the
      mechanism of p38 MAPK activation in renal epithelial cell from distal tubules
      evoked by cardiotonic steroids. Using Na+/K+ ionophores (monensin, nigericin) and
      media with different content of monovalent cations, we revealed that p38 MAPK
      phosphorylation in ouabain-treated renal epithelial cells is not caused by Na,K
      ATPase inhibition and inversion of the [Na+](i)/[K+](i) ratio. We also
      demonstrated that attenuation of pH from 7.45 to 6.75 did not alter the level of
      p38 MAPK phosphorylation observed in ouabain-treated cells. Inhibitors of PKA,
      PKC, and PKG as well as protein phosphatases were unable to abolish p38 MAPK
      activation triggered by ouabain. Using phosphotyrosine antibodies we did not
      detect any effect of ouabain on activation of tyrosine kinases. Thus, our results
      show that activation of p38 MAPK and cytotoxic action of CTS are independent of
      intracellular Na+, K+, and H+ concentrations. The molecular origin of
      intermediates of death signaling induced by CTS via conformation changes of Na,K
      ATPase with following activation of p38 MAPK should be examined further.

PMID- 21073418
TI  - Analysis of nucleolar protein fibrillarin mobility and functional state in living
      HeLa cells.
AB  - Fibrillarin is an evolutionarily-conserved and obligatory protein component of
      eukaryotic cell nucleoli involved in pre-rRNA processing and methylation. In
      vertebrates the fibrillarin molecule contains two cysteine residues (Cys99 and
      Cys268) whose sulfhydryl groups are able to establish intramolecular -S-S-
      bridges. However, the functional state of fibrillarin with reduced or oxidized
      thiol groups is still practically unstudied. Besides, there are no data in the
      literature concerning existence of the -S-S- fibrillarin form in human cells. To
      answer these questions, we used plasmids encoding native human fibrillarin and
      its mutant form devoid of cysteine residues (fibrillarinC99/268S) fused with EGFP
      for temporary transfection of HeLa cells. The mobile fraction localizing the
      enzymatically active protein molecules and the fluorescence half-recovery time
      characterizing the rate of enzymatic reactions were determined by the FRAP
      technique using a confocal laser scanning microscope. Measurements were carried
      out at 37 and 27 degrees C. The results show that the fibrillarin pool in HeLa
      cells includes two protein forms, with reduced SH groups and with oxidized SH
      groups forming intramolecular -S-S- bridges between Cys99 and Cys268. However,
      the absence of Cys99 and Cys268 has no effect on intracellular localization of
      fibrillarin and its main dynamic parameters. The human fibrillarin form without
      disulfide bridges is included into the mobile protein fraction and is consistent
      with its functionally active state.

PMID- 21073419
TI  - Isolation and crystallization of a chimeric Qbeta replicase containing Thermus
      thermophilus EF-Ts.
AB  - Qbeta replicase is a protein complex responsible for the replication of the
      genomic RNA of bacteriophage Qbeta. In addition to the phage-encoded catalytic
      beta subunit, it recruits three proteins from the host Escherichia coli cell:
      elongation factors EF-Tu and EF-Ts and ribosomal protein S1. We prepared a
      chimeric Qbeta replicase in which the E. coli EF-Ts is replaced with EF-Ts from
      Thermus thermophilus. The chimeric protein is produced in E. coli cells during
      coexpression of the genes encoding the beta subunit and thermophilic EF-Ts. The
      developed isolation procedure yields a substantially homogeneous preparation of
      the chimeric replicase. Unlike the wild-type enzyme, the S1-less chimeric
      replicase could be crystallized. This result facilitates studies on the structure
      of Qbeta replicase and the mechanism of recognition of its templates that can
      replicate in vitro at a record rate.

PMID- 21073420
TI  - Influence of organization of native protein structure on its folding: modeling of
      the folding of alpha-helical proteins.
AB  - An important question that is addressed here is whether the modeling of protein
      folding can catch the difference between the folding of proteins with similar
      structures but with different folding mechanisms. In this work, the modeling of
      folding of four alpha-helical proteins from the homeodomain family, which are
      similar in size, was done using the Monte Carlo and dynamic programming methods.
      A frequently observed order of folding of alpha-helices for each protein was
      determined using the Monte Carlo method. A correlation between the experimental
      folding rate and the number of Monte Carlo steps was also demonstrated. Amino
      acid residues that are important for the folding were determined using the
      dynamic programming method. The defined regions correlate with the order of
      folding of secondary-structure elements in the proteins both in experiments and
      in modeling.

PMID- 21073421
TI  - A new acylamidase from Rhodococcus erythropolis TA37 can hydrolyze N-substituted
      amides.
AB  - A new acylamidase was isolated from Rhodococcus erythropolis TA37 and
      characterized. N-Substituted acrylamides (isopropyl acrylamide, N,N-dimethyl
      aminopropyl acrylamide, and methylene-bis-acrylamide), acid para-nitroanilides
      (4'-nitroacetanilide, Gly-pNA, Ala-pNA, Leu-pNA), and N-acetyl derivatives of
      glycine, alanine, and leucine are good substrates for this enzyme. Aliphatic
      amides (acetamide, acrylamide, isobutyramide, n-butyramide, and valeramide) are
      also used as substrates but with less efficiency. The enzyme subunit mass by SDS
      PAGE is 55 kDa. Maximal activity is exhibited at pH 7-8 and 55 degrees C. The
      enzyme is stable for 15 h at 22 degrees C and for 0.5 h at 45 degrees C. The
      Michaelis constant (K(m)) is 0.25 mM with Gly-pNA and 0.55 mM with Ala-pNA. The
      acylamidase activity is suppressed by inhibitors of serine proteases
      (phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate) but is not
      suppressed by inhibitors of aliphatic amidases (acetaldehyde and nitrophenyl
      disulfides). The N-terminal amino acid sequence of the acylamidase is highly
      homologous to those of two putative amidases detected from sequenced R.
      erythropolis genomes. It is suggested that the acylamidase together with the
      detected homologs forms a new class within the amidase signature family.

PMID- 21073422
TI  - Inhibition of transketolase by hexacyanoferrate(III).
AB  - The effect of hexacyanoferrate(III) on the catalytic activity of transketolase
      has been studied. This oxidant inactivates only one of two active sites of the
      enzyme, the one with a higher affinity to the coenzyme (thiamine diphosphate).
      The second active site does not lose its catalytic activity. These observations
      indicate that the active sites of holotransketolase, being indiscernible by data
      of X-ray analysis, exhibit functional nonequivalence.

PMID- 21073423
TI  - Comparison of models of thrombin-binding 15-mer DNA aptamer by molecular dynamics
      simulation.
AB  - Two models of 15-mer thrombin-binding DNA aptamer (15TGT) were comparatively
      analyzed by molecular dynamics simulation using the GROMACS software package. The
      two original models of 15TGT were obtained by NMR and X-ray analyses. The models
      significantly differ in the topology of loops and the direction of
      oligodeoxyribonucleotide chain. The evolution of the two structures in parm99
      force fields and parmbsc0 optimized for nucleic acids was analyzed in our
      adaptation of GROMACS architecture. It is shown that the best system for
      description of the 15TGT structure is the model obtained by X-ray analysis in the
      parmbsc0 force field.

PMID- 21073424
TI  - Reconstruction of erythrocyte shape during modified morphological response.
AB  - Changes in erythrocyte shape during morphological response modified by
      benzalkonium chloride (BzA) were studied in sucrose solutions. Fixation of the
      cells with glutaraldehyde- and formaldehyde-containing fixatives at some time
      points is usually inadequate to maintain the current cell shape. Considering the
      reconstruction of erythrocyte shape, which takes into account the mode of
      fixative action, we showed that the echinocyte-forming activity of BzA depends on
      the concentration of this surfactant. It can induce a direct spherostomatocyte
      spheroechinocyte transition without altering the near-spherical shape of the
      cells. On the other hand, the reverse spheroechinocyte-spherostomatocyte
      transition was always accompanied by some flattening of the cells, although in
      some instances discoidal shape was not achieved. The data point to asymmetric
      shape transitions of erythrocytes in sucrose solution, which contradicts the
      continuum and bilayer-couple models of shape regulation. It seems that the
      nonuniform structure of native erythrocyte membrane plays a more important role
      in morphological transitions of these cells than suggested earlier.

PMID- 21073425
TI  - Carboxypeptidase from Streptomyces bikiniensis: primary structure, isolation, and
      properties.
AB  - A metallocarboxypeptidase produced by Streptomyces bikiniensis 27 strain (VKPM Ac
      1783) (CPSb) was purified and characterized. The enzyme cleaves both basic and
      hydrophobic C-terminal amino acid residues from synthetic peptides, that is, it
      possesses specificity of mammalian carboxypeptidases A and B. The enzyme also
      hydrolyzes peptides bearing glutamic acid at the C-end. CPSb exhibits its maximal
      activity at pH 7.0-7.6 and 55 degrees C. The nucleotide sequence encoding the
      mature CPSb in S. bikiniensis 27 (VKPM Ac-1783) genome (Accession No. GU362077)
      was determined. It is shown that the primary structure of the mature enzyme has a
      moderate degree of identity with orthologs from Streptomyces griseus (79%
      identity) and Streptomyces avermitilis (85% identity).

PMID- 21073426
TI  - Glutamine effect on cultured granule neuron death induced by glucose deprivation
      and chemical hypoxia.
AB  - Using a specific fluorescent probe of mitochondrial membrane potential
      (tetramethylrhodamine ethyl ester), we have shown that glucose deprivation (GD)
      of cultured cerebellar granule neurons (CGN) for 3 h lowers mitochondrial
      membrane potential in these cells. Longer glucose starvation (24 h) causes CGN
      death that is not prevented by blockers of ionotropic glutamate receptors (MK-801
      (10 uM) and NBQX (10 uM)). Glutamine or pyruvate (2 mM) maintain membrane
      potential of mitochondria and decrease CGN death under GD conditions. In the
      presence of glucose the mitochondrial respiratory chain blocker rotenone induces
      neuron death potentiated by glutamine. The potentiation effect is completely
      prevented by blockers of ionotropic glutamate receptors. These results show that
      glutamine under conditions of GD can be utilized by mitochondria as substrate,
      but at the same time, in the case of mitochondrial function deterioration,
      metabolism of this amino acid results in glutamate accumulation to toxic level.

PMID- 21073427
TI  - Proof of oligomeric state of frog rhodopsin: visualization of dimer and oligomers
      on gels after BN- and HRCN-PAGE using antibodies to rhodopsin and by retinylopsin
      fluorescence.
AB  - Staining by antibodies to rhodopsin (Rh) and fluorescence of N-retinylopsin (RO)
      have shown that digitonin (DIG)- , dodecyl-beta-D-maltoside (DM)- , and sodium
      dodecyl sulfate (SDS)-solubilized frog Rh after BN- and HRCN-PAGE is situated in
      the gradient gel in the state of dimer with a slight content of higher oligomers
      (trimer, tetramer, etc.). With increasing detergent harshness (DIG < DM < SDS),
      the proportion of higher oligomers in extracts becomes more prominent. Formation
      of RO in rod outer segments (ROS) in the presence of 0.7 M NaBH(3)CN at pH 5.0
      occurs only when Rh is simultaneously photolyzed during reduction. Dithiothreitol
      at the concentration of 0.005 M failed to induce RO production. Formation of a
      stable C-N bond between all-trans-retinal and opsin in RO is accompanied by
      decrease in the dimer share and increase in the share of the higher oligomers due
      to secondary dissociation-aggregation of solubilized opsin. The position of the
      Rh dimer in relation to the anode during both native electrophoreses is
      determined not only by its molecular mass, but probably also depends on unfolding
      degree (or form): the harsher the detergent, the closer to the anode the dimer is
      located. Treatment of ROS by agents modifying the cholesterol component of lipid
      membrane (MbetaCD, filipin III, nystatin, saponin) did not change the character
      of Rh oligomerization, thus showing that integrity of the cholesterol component
      of photoreceptor membrane is not a crucial factor for oligomerization of opsin.
      It is supposed that the dimer-oligomer "portrait" of frog Rh, which has been
      found by two methods of native electrophoresis in three detergents with different
      degree of harshness, corresponds to a physiological state of this protein in
      native photoreceptor membrane.

PMID- 21073428
TI  - Inorganic polyphosphate in the yeast Saccharomyces cerevisiae with a mutation
      disturbing the function of vacuolar ATPase.
AB  - A mutation in the vma2 gene disturbing V-ATPase function in the yeast
      Saccharomyces cerevisiae results in a five- and threefold decrease in inorganic
      polyphosphate content in the stationary and active phases of growth on glucose,
      respectively. The average polyphosphate chain length in the mutant cells is
      decreased. The mutation does not prevent polyphosphate utilization during
      cultivation in a phosphate-deficient medium and recovery of its level on
      reinoculation in complete medium after phosphate deficiency. The content of short
      chain acid-soluble polyphosphates is recovered first. It is supposed that these
      polyphosphates are less dependent on the electrochemical gradient on the vacuolar
      membrane.

PMID- 21073429
TI  - Point mutations in Pma1 H+-ATPase of Saccharomyces cerevisiae: influence on its
      expression and activity.
AB  - Yeast Pma1 H+-ATPase is a key enzyme of cell metabolism generating
      electrochemical proton gradient across the plasma membrane, thus playing an
      important role in the maintenance of ion homeostasis in the cell. Using site
      directed mutagenesis, we have previously replaced all 21 amino acid residues in
      the transmembrane segment M8 with Ala (Guerra et al. (2007) Biochim. Biophys.
      Acta, 1768, 2383-2392). In this work, we present new data on the role of these
      amino acid residues in the structure-function relationship in the enzyme and cell
      tolerance to heat shock. Mutations Q798A and I799A are lethal for cells
      regardless of expression of the enzyme in secretory vesicles or plasma membrane.
      The F796A mutation causes enzyme and cell sensitivity to heat shock when
      expressed in secretory vesicles. The I794A mutation increases temperature
      sensitivity of cells when the enzyme is expressed either in secretory vesicles
      or, to a lesser extent, in plasma membrane. The E803A mutation has no significant
      influence on the ATPase and cell sensitivity to heat shock; however, it causes a
      shift in the equilibrium between E1 and E2 conformations of the enzyme towards
      E1.

PMID- 21073430
TI  - Future targeted disease modifying drugs for Alzheimer's disease.
AB  - Alzheimer's disease is the most common form of dementia. Alzheimer's disease will
      be responsible for an enormous burden on the individual and the society, as with
      the aging of the population, the incidence and the prevalence will grow.
      Presently, the drugs used in Alzheimer's disease are only effective
      symptomatically and improve functioning. They do not halt the progression of the
      disease. With the recent advances in our understanding of the pathogenesis of
      this disease, there have been tremendous advances in the clinical trials of
      compounds that can modify the disease process. Numerous therapeutic interventions
      and neuroprotective approaches are also in trial phase. It seems that in near
      future some of these compounds may be found effective and safe for use in this
      disease there by reducing the incidence of this disease in years to come, thereby
      lessen the burden due to it. In this article various compounds that can modify
      the course of the disease are discussed. Some recent patents and inventions for
      the treatment of Alzheimer's disease have also been discussed.

PMID- 21073431
TI  - Towards drug discovery for brain tumours: interaction of kinins and tumours at
      the blood brain barrier interface.
AB  - Cancers of the brain are intrinsically more complicated to treat than systemic
      malignancies due to the unique anatomical features of the brain. The blood-brain
      barrier prevents chemotherapeutic agents from reaching brain neoplasms, and
      angiogenesis occurs as the metabolic needs of the tumour increase, thus further
      complicating treatment. The newly formed blood vessels form the blood-tumour
      barrier and are distinct from the blood-brain barrier in that they are more
      permeable. Being more permeable, these abnormal blood vessels lead to the
      formation of peri-tumoural edema, which is the cause of much morbidity and
      mortality associated with central nervous system neoplasms. While the cause of
      the increased permeability is unclear, kinins have been implicated in regulating
      the permeability of normal vasculature. Kinins are also known to exert many
      inflammatory actions affecting both normal and angiogenic blood vessels, as well
      as tumour cells. The vasodilatory and vascular permeabilizing effects of kinins,
      and particularly bradykinin and substance P, have been investigated with regard
      to delivery of chemotherapeutic agents to neoplastic brain tissue through both
      vascular barriers. In contrast, kinin receptor antagonists have been found to
      exert effects on tumour cells that result in decreased angiogenesis, tumour cell
      motility and growth. Thus, many recent patents describe kinin activity on brain
      vasculature, which may play an integral role in the development of treatments for
      malignancies in the central nervous system through amelioration of angiogenesis.
      In conjunction, patents that discuss the ability of kinins to decrease tumour
      cell migration and proliferation demonstrate that kinins may offer novel
      approaches to brain tumour therapy in the future.

PMID- 21073432
TI  - Recent developments in therapeutic approaches for lysosomal storage diseases.
AB  - Genetic mutations that cause specific lysosomal protein deficiencies account for
      more than 45 Lysosomal Storage Diseases (LSDs), mostly pre-adult disorders which
      are associated with neurological symptoms and mental retardation. Interestingly,
      such diseases are often characterized by intracellular deposition and protein
      aggregation, events also found in age-related neurodegenerative diseases. During
      the past twenty years, different approaches have been introduced for the
      treatment of these disorders, several of which are now in routine clinical use or
      clinical trials. Among them, enzyme replacement therapy (ERT) represented a major
      progress. However, the usefulness of ERT is limited due to the fact that enzyme
      distribution is insufficient and treatment costs are very high. A further novel
      therapeutic option for LSDs is based on the use of small molecules, that can
      either inhibit a key enzyme which is responsible for substrate synthesis
      (substrate reduction) or act as a chaperone to increase the residual activity of
      the lysosomal enzyme (pharmacological chaperones). In addition, recently various
      gene therapy approaches have been developed, mostly based on adeno-associated and
      lentiviral vectors, and strategies based on stem cells administration are
      beginning their route. This review provides an update of the status of research
      on LSDs therapeutic approaches, including recent patents in the field.

PMID- 21073433
TI  - Current and future therapies of erectile dysfunction in neurological disorders.
AB  - Erection is a neurovascular event characterized by the tumescence of the
      cavernous bodies that relies upon integration of neural and humoral mechanisms
      requiring the participation of autonomic and somatic nerves and the integration
      of numerous spinal and supraspinal sites. Erectile dysfunction (ED) is a highly
      prevalent problem increasing with age, as well as the major men's sexual concern.
      Significant advances in the pharmacological treatment of ED have occurred in
      recent years, most notably after the introduction of sildenafil, the first oral
      selective phosphodiesterase type 5 inhibitor. Nevertheless, many other oral,
      local and surgical treatments are available and their efficacy and safety depend
      on the specific cases. This review provides a comprehensive description of both
      currently available neurogenic ED treatments and most promising future therapies,
      including assigned patents.

PMID- 21073434
TI  - Crystal structure and cytotoxic activity of Co(II) complex containing N,N'-tetra
      (4-antipyrylmethyl)-1,2-diaminoethane (TAMEN) as ligand.
AB  - The mononuclear complex, [Co(TAMEN)](ClO(4))(2) (DMSO), containing the Mannich
      base N,N'-tetra-(4-antipyrylmethyl)-1,2-diaminoethane (TAMEN) as ligand, was
      synthesized and characterised by conductometric, electronic and infrared
      spectroscopic properties. The single-crystal X-ray structure show the presence of
      two well defined units, [Co(TAMEN)](2+) and (ClO(4))(-). The complex cation
      contains cobalt(II) in the pseudo octahedral environment created by the N(2)O(4)
      donor set of TAMEN. The cobalt(II) complex have been screened for its cytotoxic
      activity against three cultured human cell lines established from hepatoma (Hep
      G2), breast (MCF-7) and lung (A549) cancers as well as on non-tumor bovine kidney
      (MDBK) cells. The cytotoxic activity of the ligand TAMEN was assessed on one
      tumor (Hep G2) and one non-tumor (MDBK) cell lines. The cobalt(II) compound was
      found to decrease in a time- and concentration- dependent manner the viability of
      tumor (A549, MCF-7, Hep G2) cell lines, while the ligand TAMEN expressed
      proliferative activity on hepatoma (HepG2) and bovine kidney (MDBK) cells,
      especially after prolonged incubation.

PMID- 21073435
TI  - Synthesis and in vitro evaluation of some isatin-thiazolidinone hybrid analogues
      as anti-proliferative agents.
AB  - A range of isatin-thiazolidinone hybrid analogues were synthesized and their
      cytotoxicity was evaluated against several cancer cell lines in vitro. The acute
      toxicity studies in mice models revealed that these analogues possess low
      systemic toxicity and are safe up to 1600mg/Kg. Among the compounds synthesized,
      5-(2-nitrobenzylidene)-2-(isatin-3-azino)-thiazolidin-4-one (CI) has been shown
      to be the most active, highly promising compound which induced S phase arrest in
      cell cycle in a time dependent manner. Our initial analysis indicate that
      incorporation of electron withdrawing group at ortho position of the ring favors
      over the meta and para positions for eliciting its cytostatic effect. Overall,
      the in vitro biological evaluation suggests that the growth inhibitory effect of
      CI is promising and can be studied further.

PMID- 21073436
TI  - Recent patents of DNA methylation biomarkers in gastrointestinal oncology.
AB  - Gastrointestinal malignancies are among the most common malignancies worldwide.
      Advances in technology and treatment have improved diagnosis and monitoring of
      these tumors. As a consequence, identification of new biomarkers that can be
      applied at different levels of disease is urgently needed. DNA methylation is a
      process in which cytosines acquire a methyl group in 5' position only if they are
      followed by a guanine. An emerging catalog of specific genes inactivated by DNA
      methylation in gastrointestinal tumors has been established. In this review we
      will give a brief overview of the main sources of DNA used to investigate
      methylation biomarkers and several related patents. One of these is related to
      multiple genes that predict the risk of development of esophageal adenocarcinoma.
      Another evaluated methylation status of 24 genes to find one frequently
      methylated in primary tumors as well as plasma samples from gastric cancer
      patients. Others patented the epigenetic silencing of miR-342 as a promissory
      biomarker for colorectal carcinoma. Thus the new field of DNA methylation
      biomarkers holds the promise of better methods for screening, early detection,
      disease progression and outcome predictor of therapy response in gastrointestinal
      oncology.

PMID- 21073437
TI  - Recent patents of nanopore DNA sequencing technology: progress and challenges.
AB  - DNA sequencing techniques witnessed fast development in the last decades,
      primarily driven by the Human Genome Project. Among the proposed new techniques,
      Nanopore was considered as a suitable candidate for the single DNA sequencing
      with ultrahigh speed and very low cost. Several fabrication and modification
      techniques have been developed to produce robust and well-defined nanopore
      devices. Many efforts have also been done to apply nanopore to analyze the
      properties of DNA molecules. By comparing with traditional sequencing techniques,
      nanopore has demonstrated its distinctive superiorities in main practical issues,
      such as sample preparation, sequencing speed, cost-effective and read-length.
      Although challenges still remain, recent researches in improving the capabilities
      of nanopore have shed a light to achieve its ultimate goal: Sequence individual
      DNA strand at single nucleotide level. This patent review briefly highlights
      recent developments and technological achievements for DNA analysis and
      sequencing at single molecule level, focusing on nanopore based methods.

PMID- 21073439
TI  - Incidence and risk factors for tenofovir-associated renal function decline among
      Thai HIV-infected patients with low-body weight.
AB  - OBJECTIVES: we aimed at determining the incidence and factors for TDF-associated
      renal function decline among Thai HIV-infected patients. METHODS: retrospective
      and prospective cohort studies were conducted. We enrolled HIV-infected adults
      who had initiated TDF. Renal function decline that was defined by a decrease of
      25% in glomerular filtration rate (GFR) from the baseline. Factors associated
      with the renal function decline were determined. RESULTS: a total of 405 patients
      with a median (IQR) body weight of 56.5 (50.5-65.0) kg were enrolled. All but
      four (99%) were antiretroviral treatment-experience patients. A median (IQR)
      duration of receiving TDF was 16 (8-21) months. Of these, 78 (19.3%) patients had
      a 25% decrease in GFR with the incidence rate of 16.2 per 100 person-years. By
      Kaplan-Meier survival analysis, median time to a 25% decrease in GFR was 28 [95%
      confidence interval (CI) 25.2-30.8] months. By multiple logistic regression,
      lower body weight [odds ratio (OR) 1.15 per 5 kg, 95% CI 1.00-1.33], lower body
      mass index (BMI) (OR 2.26 per 1 kg/m(2), 95% CI 1.74-2.94), baseline GFR (OR 1.62
      per 10 ml/min/1.73m(2), 95% CI 1.39-1.88), protease inhibitor (OR 2.12, 95% CI
      1.15-3.92), and nephrotoxic drug (OR 3.16, 95% CI 1.44-6.98) were statistically
      significant factors associated with a 25% decrease in GFR. CONCLUSIONS: the study
      revealed high incidence of TDF-associated renal function decline among patients
      with low-body weight and BMI. Additional risk factors were baseline GFR,
      receiving protease inhibitor, and nephrotoxic drugs. Close monitoring of renal
      function is warranted among patients with these risk factors.

PMID- 21073438
TI  - Analysis of HIV tropism in Ugandan infants.
AB  - HIV-infected infants may have CXCR4-using (X4-tropic) HIV, CCR5-using (R5-tropic)
      HIV, or a mixture of R5-tropic and X4-tropic HIV (dual/mixed, DM HIV). The level
      of infectivity for R5 virus (R5-RLU) varies among HIV infected infants. HIV
      tropism and R5-RLU were measured in samples from HIV-infected Ugandan infants
      using a commercial assay. DM HIV was detected in 7/72 (9.7%) infants at the time
      of HIV diagnosis (birth or 6-8 weeks of age, 4/15 (26.7%) with subtype D, 3/57
      (5.3 %) with other subtypes, P=0.013). A transition from R5-tropic to DM HIV was
      observed in only two (6.7%) of 30 infants over 6-12 months. Six (85.7%) of seven
      infants with DM HIV died, compared to 21/67 (31.3%) infants with R5-tropic HIV
      (p=0.09). Higher R5-RLU at 6-8 weeks was not associated with decreased survival.
      Infants with in utero infection had a higher median R5-RLU than infants who were
      HIV-uninfected at birth (p=0.025).

PMID- 21073440
TI  - Profile of HIV-1 infected patients from an AIDS clinic in Beijing from 2007-2008.
AB  - While significant progress has been made since 2003 when a comprehensive
      treatment, prevention and control program was implemented to combat the HIV/AIDS
      epidemic in China, new challenges are emerging. There have been limited direct
      case reports on profiles of HIV/AIDS patients under care at unique clinical
      settings in China despite significant differences between clinics in this part of
      the world and those in Western countries. In this report, characteristics of
      HIV/AIDS patients managed during a 12-month period from June 2007 to May 2008 at
      a major medical school-affiliated AIDS clinic in the center of Beijing are
      described. Our data confirm an alarming trend of increased rates of sexual
      transmission of HIV-1 in recent years and suggest that major improvements are
      needed for both the type of antiviral treatments being used and post-treatment
      monitoring of viral load. This information will be useful for the continued
      progress in the clinical management of HIV/AIDS patients in China.

PMID- 21073441
TI  - Do HIV-Infected Immigrants Initiating HAART have Poorer Treatment-Related
      Outcomes than Autochthonous Patients in Spain? Results of the GESIDA 5808 Study.
AB  - OBJECTIVE: currently, 12% of the Spanish population is foreign-born, and a third
      of newly diagnosed HIV-infected patients are immigrants. We determined whether
      being an immigrant was associated with a poorer response to antiretroviral
      treatment. METHODS: historical multicenter cohort study of naive patients
      starting HAART. The primary endpoint was time to treatment failure (TTF) defined
      as virological failure (VF), death, opportunistic disease, treatment
      discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed
      as observed data (TFO; censoring missing patients) and time to virological
      failure (TVF; censoring missing patients and D/C not due to VF). A multivariate
      analysis was performed to control for confounders. RESULTS: a total of 1090
      treatment-naive HIV-infected patients (387 immigrants and 703 autochthonous) from
      33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%)
      or South-Central America/Caribbean (31%). Immigrants were significantly younger
      (34 y vs. 39 y), more frequently female (37.5% vs. 24.6%), with less HCV
      coinfection than autochthonous patients (7% vs. 31.3%). There were no differences
      in baseline viral load (4.95 Log(10) vs. 4.98 Log(10)), CD4 lymphocyte count
      (193.5/uL vs. 201.5/uL), late initiation of HAART (56.4% vs. 56.0%), or
      antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show
      differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57
      1.78) between immigrants and autochthonous patients. Losses to follow-up were
      more frequent among immigrants (17.8% vs. 12.1; p=0.009). Sub-Saharan African
      patients and immigrant females had a significantly shorter TTF. CONCLUSIONS: the
      response to HAART among immigrant patients was similar to that of autochthonous
      patients, although they had a higher rate of losses to follow-up. Sub-Saharan
      Africans and immigrant females may need particular measures to avoid barriers
      hindering antiviral efficacy.

PMID- 21073443
TI  - High-cell density-induced VCAM1 expression inhibits the migratory ability of
      mesenchymal stem cells.
AB  - MSCs (mesenchymal stem cells) migrate into damaged tissue and then proliferate
      and differentiate into various cell lineages to regenerate bone, cartilage, fat
      and muscle. Cell-cell adhesion of MSCs is essential for the MSC-dependent tissue
      regeneration after their homing into a damaged tissue. However, it remains to be
      elucidated what kinds of adhesion molecules play important roles in the cell-cell
      communication between MSCs. In order to identify adhesion molecules that
      facilitate mutual contact between MSCs, a comprehensive analysis of mRNA
      expression in adhesion molecules was performed by comparing profiles of
      expression status of adhesion molecules in MSCs at low- and high-cell density. We
      found that the expression level of VCAM1 (vascular cell adhesion molecule
      1)/CD106 was clearly up-regulated in the human bone marrow-derived MSCs-UE7T-13
      cells - under a condition of high cell density. Intriguingly, the migratory
      ability of the cells was clearly accelerated by a knockdown of VCAM1.
      Furthermore, the migratory ability of UE7T-13 cells was decreased by the over
      expression of exogenous VCAM1. In addition, the high cell density-induced
      expression of VCAM1 was clearly suppressed by NF-kappaB (nuclear factor-kappaB)
      signalling-related protein kinase inhibitors such as an IKK-2 (IkappaB kinase-2)
      inhibitor VI. In conclusion, the high cell density-induced VCAM1 expression
      through the NF-kappaB pathway inhibits the migratory ability of human bone marrow
      derived MSCs.

PMID- 21073442
TI  - Differential effects of efavirenz and lopinavir/ritonavir on human adipocyte
      differentiation, gene expression and release of adipokines and pro-inflammatory
      cytokines.
AB  - In the present study, a comparative assessment of the effects of efavirenz (EFV)
      and lopinavir/ritonavir (LPV/r; 4:1) on human adipocytes in culture has been
      performed. Human pre-adipocytes were treated with EFV or LPV/r during or after
      adipogenic differentiation. Acquisition of adipocyte morphology, expression of
      gene markers of mitochondrial toxicity, adipogenesis and inflammation, and
      release of adipokines and cytokines to the medium were measured. Results
      indicated that EFV and LPV/r impaired adipocyte differentiation in association
      with a reduction in transcript levels for adipogenic differentiation genes
      (adiponectin, lipoprotein lipase, leptin) and master regulators of adipogenesis
      (PPAR, C/EBP). The effects were greater with EFV than LPV/r. Both LPV/r and EFV
      induced increases in monocytechemoattactant protein-1 (MCP-1) mRNA levels, but
      the effect was greater with EFV. Similarly, the release of proinflammatory
      cytokines and other inflammation-related molecules (interleukins 6 and 8, MCP-1,
      PAI-1) was enhanced to a much higher degree by EFV than by LPV/r. Adiponectin and
      leptin release by adipocytes was reduced by both drugs, although to a higher
      extent by EFV. Neither drug affected mitochondrial DNA levels, transcripts
      encoding mitochondrial proteins or lactate release by adipocytes. In previously
      differentiated adipocytes, EFV caused a significant reduction in PPARgamma and
      adiponectin expression, whereas LPV/r did not. We conclude that both EFV and
      LPV/r impair human adipogenesis, reduce adipokine release and increase the
      expression and release of inflammation-related cytokines, but the overall effects
      are greater with EFV. These findings may have implications for the pathogenesis
      of HIV-1-associated lipodystrophy and the development of HIV-1 therapies.

PMID- 21073444
TI  - Regulation of pendrin by pH: dependence on glycosylation.
AB  - Mutations in the anion exchanger pendrin are responsible for Pendred syndrome, an
      autosomal recessive disease characterized by deafness and goitre. Pendrin is
      highly expressed in kidney collecting ducts, where it acts as a
      chloride/bicarbonate exchanger and thereby contributes to the regulation of acid
      base homoeostasis and blood pressure. The present study aimed to characterize the
      intrinsic properties of pendrin. Mouse pendrin was transfected in HEK (human
      embryonic kidney) 293 and OKP (opossum kidney proximal tubule) cells and its
      activity was determined by monitoring changes in the intracellular pH induced by
      variations of transmembrane anion gradients. Combining measurements of pendrin
      activity with mathematical modelling we found that its affinity for Cl-, HCO3-
      and OH- varies with intracellular pH, with increased activity at low
      intracellular pH. Maximal pendrin activity was also stimulated at low
      extracellular pH, suggesting the presence of both intracellular and extracellular
      proton regulatory sites. We identified five putative pendrin glycosylation sites,
      only two of which are used. Mutagenesis-induced disruption of pendrin
      glycosylation did not alter its cell-surface expression or polarized targeting to
      the apical membrane and basal activity, but fully abrogated its sensitivity to
      extracellular pH. The hither to unknown regulation of pendrin by external pH may
      constitute a key mechanism in controlling ionic exchanges across the collecting
      duct and inner ear.

PMID- 21073445
TI  - The expressions of the SOX trio, PTHrP (parathyroid hormone-related peptide)/IHH
      (Indian hedgehog protein) in surgically induced osteoarthritis of the rat.
AB  - This study was performed to investigate the expressions of the SOX trio, PTHrP
      (parathyroid hormone-related peptide) and IHH (Indian hedgehog protein) in OA
      (osteoarthritis) using surgically induced rat OA model. After 12 weeks, the
      articular cartilage from the distal femur was harvested. The expressions of the
      SOX trio, PTHrP and IHH were explored at gene, protein and epigenetic levels by
      real-time PCR (n = 5), immunohistochemistry (n = 5) and MSP (methylation-specific
      PCR). The findings from OA cartilage of the right knees were compared with those
      from the left knees as the control. The gene expressions of SOX-5, -6, -9
      decreased by 58, 20 and 40%, respectively, in the OA cartilage, while their
      respective protein expressions increased. The PTHrP and IHH gene expressions
      decreased by 75 and 81%, respectively, although their protein expressions
      increased. Findings from MSP demonstrated increased methylation in the promoter
      regions of SOX-5 and -9 genes. This study demonstrated that increased methylation
      in the promoters of these genes may explain the low gene expression in the
      surgically induced OA model, whereas elevated protein expression is speculated to
      be from lag effect in the gene-protein expression.

PMID- 21073446
TI  - Differentiation of AFS cells derived from the EGFP gene transgenic porcine
      fetuses.
AB  - We have obtained the EGFP (enhanced green fluorescence protein) gene transgenic
      porcine fetuses before. The aims of this study were (i) to determine whether stem
      cells could be isolated from amniotic fluid of the transgenic porcine fetuses,
      and (ii) to determine if these stem cells could express EGFP and differentiate in
      vitro. The results demonstrated that stem cells could be isolated from amniotic
      fluid of the EGFP gene transgenic porcine fetuses and could express EGFP and
      differentiate in vitro. Undifferentiated AFSs (amniotic fluid-derived stem cells)
      expressed POU5F1, THY1 and SOX2, while the following differentiation cells
      expressed markers for chondrogenic (COL2A1), osteogenic (osteocalcin and
      osteonectin) and neurogenic cells such as astrocyte (GFAP), oligodendrocyte
      (GALC) and neuron (NF, ENO2 and MAP).

PMID- 21073447
TI  - Lack of association between ADIPOQ rs266729 and ADIPOQ rs1501299 polymorphisms
      and cardiovascular disease in rheumatoid arthritis patients.
AB  - To assess the potential association between ADIPOQ rs266729 and rs1501299 gene
      polymorphisms, either isolated or in combination, and cardiovascular disease in
      patients with rheumatoid arthritis (RA), 674 patients seen at the rheumatology
      outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos,
      Madrid, Spain, were analyzed. Genotyping was performed using predesigned TaqMan
      assays (Applied Biosystems, Foster City, CA). Carotid intima-media thickness,
      flow-mediated endothelium-dependent and endothelium-independent post
      nitroglycerin vasodilatation, which are used as surrogate markers of subclinical
      atherosclerosis, were measured in a subsample. No significant differences in the
      genotype, allele or allele combination frequencies of both polymorphisms were
      found between RA patients with or without cardiovascular events or subclinical
      atherosclerosis. Therefore, ADIPOQ rs266729 and rs1501299 polymorphisms do not
      seem to be associated with cardiovascular disease in RA.

PMID- 21073448
TI  - CEDNIK syndrome results from loss-of-function mutations in SNAP29.
AB  - BACKGROUND: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma)
      syndrome is a rare genodermatosis which was shown 5 years ago in one family to be
      associated with a loss-of-function mutation in SNAP29, encoding a member of the
      SNARE family of proteins. Decrease in SNAP29 expression was found to result in
      abnormal lamellar granule maturation leading to aberrant epidermal
      differentiation and ichthyosis. OBJECTIVES: To delineate the molecular
      consequences of disease-causing mutations in SNAP29. METHODS: We used direct
      sequencing, in vitro mutagenesis and three-dimensional organotypic cell cultures.
      RESULTS: We identified a novel homozygous insertion in SNAP29 (c.486insA) in two
      sibs presenting with ichthyosis and dysgenesis of the corpus callosum. In vitro
      transfection experiments indicated that this mutation results in SNAP29 loss-of
      function. Further substantiating this notion, we could replicate histological
      features typical for CEDNIK syndrome in three-dimensional primary human
      keratinocyte organotypic cell cultures downregulated for SNAP29. CONCLUSIONS: The
      identification of a second mutation in SNAP29 in the present study definitely
      establishes a causal relationship between defective function of SNAP29 and the
      pleiotropic manifestations of CEDNIK syndrome. Our present and previous data
      position SNAP29 as an essential component of the epidermal differentiation
      machinery.

PMID- 21073450
TI  - "Same same but different": replicated ecological speciation at White Sands.
AB  - Understanding the factors that promote or inhibit species formation remains a
      central focus in evolutionary biology. It has been difficult to make generalities
      about the process of ecological speciation in particular given that each example
      is somewhat idiosyncratic. Here we use a case study of replicated ecological
      speciation in the same selective environment to assess factors that account for
      similarities and differences across taxa in progress towards ecological
      speciation. We study three different species of lizards on the gypsum sand dunes
      of White Sands, New Mexico, and present evidence that all three fulfill the
      essential factors for ecological speciation. We use multilocus nuclear data to
      show that progress toward ecological speciation is unequal across the three
      species. We also use morphometric data to show that traits other than color are
      likely under selection and that selection at White Sands is both strong and
      multifarious. Finally, we implicate geographic context to explain difference in
      progress toward speciation in the three species. We suggest that evaluating cases
      from the natural world that are "same same but different" can reveal the
      mechanisms of ecological speciation.

PMID- 21073449
TI  - Validity of The Health Improvement Network (THIN) for the study of psoriasis.
AB  - BACKGROUND: Psoriasis is a common disease frequently studied in large databases.
      To date the validity of psoriasis information has not been established in The
      Health Improvement Network (THIN). OBJECTIVES: To investigate the validity of
      THIN for identifying patients with psoriasis and to determine if the database can
      be used to determine the natural history of the disease. METHODS: First, we
      conducted a cross-sectional study to determine if psoriasis prevalence in THIN is
      similar to expected. Second, we created a cohort of 4900 patients, aged 45-64
      years, with a psoriasis diagnostic Read Code and surveyed their general
      practitioners (GPs) to confirm the diagnosis clinically. Third, we created models
      to determine if psoriasis descriptors (extent, severity, duration and
      dermatologist confirmation) could be accurately captured from database records.
      RESULTS: Psoriasis prevalence was 1.9%, and showed the characteristic age
      distribution expected. GP questionnaires were received for 4634 of 4900 cohort
      patients (95% response rate), and psoriasis diagnoses were confirmed in 90% of
      patients. Duration of disease in the database showed substantial agreement with
      physician query (kappa = 0.69). GPs confirmed that the psoriasis diagnosis was
      corroborated by a dermatologist in 91% of patients whose database records
      contained a dermatology referral code associated with a psoriasis code. We
      achieved good discrimination between patients with and without extensive disease
      based on the number of psoriasis codes received per year (area under curve =
      0.8). CONCLUSIONS: THIN is a valid data resource for studying psoriasis and can
      be used to identify characteristics of the disease such as duration and
      confirmation by a dermatologist.

PMID- 21073451
TI  - North American origin and recent European establishments of the amphi-Atlantic
      peat moss Sphagnum angermanicum.
AB  - Genetic and morphological similarity between populations separated by large
      distances may be caused by frequent long-distance dispersal or retained ancestral
      polymorphism. The frequent lack of differentiation between disjunct conspecific
      moss populations on different continents has traditionally been explained by the
      latter model, and has been cited as evidence that many or most moss species are
      extremely ancient and slowly diverging. We have studied intercontinental
      differentiation in the amphi-Atlantic peat moss Sphagnum angermanicum using 23
      microsatellite markers. Two major genetic clusters are found, both of which occur
      throughout the distributional range. Patterns of genetic structuring and overall
      migration patterns suggest that the species probably originated in North America,
      and seems to have been established twice in Northern Europe during the past
      40,000 years. We conclude that similarity between S. angermanicum populations on
      different continents is not the result of ancient vicariance and subsequent
      stasis. Rather, the observed pattern can be explained by multiple long-distance
      dispersal over limited evolutionary time. The genetic similarity can also partly
      be explained by incomplete lineage sorting, but this appears to be caused by the
      short time since separation. Our study adds to a growing body of evidence
      suggesting that Sphagnum, constituting a significant part of northern hemisphere
      biodiversity, may be more evolutionary dynamic than previously assumed.

PMID- 21073452
TI  - Polybacterial challenge enhances HIV reactivation in latently infected
      macrophages and dendritic cells.
AB  - A polymicrobial infection comprising subgingival biofilms is the trigger for the
      chronic immunoinflammatory lesions of periodontitis. These microbial biofilms
      interface with host immune cells that increase with progressing disease and could
      result in HIV reactivation in HIV-1-infected patients. Previous reports have
      focused on the ability of monospecies challenge of macrophages and dendritic
      cells to detail molecular aspects of their detection and signalling pathways.
      This study provides a seminal description of the responses of macrophages and
      dendritic cells to a polybacterial challenge using various oral bacteria as
      prototype stimuli to examine these response characteristics. The investigation
      employed a model of HIV-promoter activation and reactivation of HIV viral
      replication. Oral Gram-negative bacteria elicited significantly greater levels of
      HIV promoter activation and viral replication from all cell types, compared with
      Gram-positive bacteria. Selected combinations of oral Gram-negative bacteria
      elicited synergistic HIV promoter activation and viral replication in macrophages
      and immature dendritic cells. In mature dendritic cells, there was no synergism
      in HIV promoter activation and viral replication. Gram-positive bacteria showed
      no synergism in any cell model. These findings support the importance of
      determining the characteristics and impact of polybacterial challenges on immune
      cells to clarify the potential immune recognition and antigen processing that can
      occur in the oral cavity.

PMID- 21073453
TI  - Elastic anisotropy and off-axis ultrasonic velocity distribution in human
      cortical bone.
AB  - Elastic structure in cortical bone is usually simplified as orthotropic or
      transversely isotropic, which allows estimates of three-dimensional technical
      constants from ultrasonic and density measurements. These elastic property
      estimates can then be used to study phenotypic changes in cortical bone structure
      and function, and to create finite element models of skeletal structures for
      studies of organismal variation and functional adaptation. This study examines
      assumptions of orthotropic or transversely isotropic material structure in
      cortical bone through the investigation of off-axis ultrasonic velocities in the
      cortical plane in 10 samples each from a human femur, mandible and cranium.
      Longitudinal ultrasonic velocities were measured twice through each bone sample
      by rotating the perimeter of each sample in 1  degrees  angular intervals between
      two ultrasonic transducers. The data were fit to sine curves f(x)=(A * sin(x + B)
      + C) and the goodness of fit was examined. All the data from the femur fit
      closely with the ideal sine curve model, and all three coefficients were similar
      among specimens, indicating similar elastic properties, anisotropies and
      orientations of the axes of maximum stiffness. Off-axis ultrasonic velocities in
      the mandible largely fit the sine curve model, although there were regional
      variations in the coefficients. Off-axis ultrasonic velocities from the cranial
      vault conformed to the sine curve model in some regions but not in others, which
      shows an irregular and complex pattern. We hypothesize that these variations in
      ultrasonic velocities reflect variations in the underlying bulk microstructure of
      the cortical bone, especially in the three-dimensional patterns of osteonal
      orientation and structure. Elastic property estimates made with ultrasonic
      techniques are likely valid in the femur and mandible; errors in estimates from
      cranial bone need to be evaluated regionally. Approximate orthotropic structure
      in bulk cortical bone specimens should be assessed if ultrasound is used to
      estimate three-dimensional elastic properties.

PMID- 21073454
TI  - Ecological conditions in wintering and passage areas as determinants of timing of
      spring migration in trans-Saharan migratory birds.
AB  - 1. Climate change has been associated with shifts in the timing of biological
      events, including the spring arrival of migratory birds. Early arrival at
      breeding sites is an important life-history trait, usually associated with higher
      breeding success and therefore, susceptible to selection and evolution in
      response to changing climatic conditions. 2. Here, we examine the effect of
      changes in the environmental conditions of wintering and passage areas on the
      mean passage time of 13 trans-Saharan passerines during their spring migration
      through the western Mediterranean over the 15 years from 1993 to 2007. 3. We
      found that most of the species studied have been advancing the timing of their
      passage in recent years. However, annual variation in the mean date of passage
      was positively correlated with vegetation growth (measured as the normalized
      difference vegetation index [NDVI]) both in the Sahel (the region of departure)
      and in northern Africa (the passage area). Thus, migration dates were delayed in
      years with high primary productivity in passage and wintering zones. All species
      seem to respond similarly to NDVI in the Sahel; however, late migrants were less
      affected by ecological conditions in northern Africa than those migrating
      earlier, suggesting differences based on species ecology. 4. Mean timing of
      passage was not related to the North Atlantic Oscillation (NAO), El Nino-Southern
      Oscillation (ENSO), temperature or NDVI in the species-specific wintering areas
      (the overwintering region) when analysed in combination with the other
      covariates. 5. Our findings show that ecological conditions in the winter
      quarters (specifically the Sahel) and en route are relevant factors influencing
      trends in the passage dates of trans-Saharan migratory birds on the southern
      fringe of Europe. Possible long-term consequences for late arriving spring
      migrants are discussed.

PMID- 21073455
TI  - Effects of early horn growth on reproduction and hunting mortality in female
      chamois.
AB  - 1. Environmental conditions during early development can affect the growth
      patterns of vertebrates, influencing future survival and reproduction. In long
      lived mammals, females that experience poor environmental conditions early in
      life may delay primiparity. In female bovids, annual horn growth increments may
      provide a record of age-specific reproduction and body growth. Horn length,
      however, may also be a criterion used by hunters in selecting animals to harvest,
      possibly leading to artificial selection. 2. We studied three populations of
      chamois (Rupicapra rupicapra) in the western Alps to explore the relationships
      between female horn length and early growth, age of primiparity and age-specific
      reproduction. We also compared the risk of harvest to reproductive status and
      horn length. 3. Early horn growth was positively correlated with body mass in pre
      reproductive females and with reproduction in very young and senescent adults.
      Females with strong early horn growth attained primiparity at an earlier age than
      those with weak early growth. Horn length did not affect hunter selection, but we
      found a strong hunter preference for nonlactating females. 4. Our research
      highlights the persistent effects of early development on reproductive
      performance in mammals. Moderate sport harvests are unlikely to affect the
      evolution of phenotypic traits and reproductive strategies in female chamois. A
      policy of penalizing hunters that harvest lactating females, however, may
      increase the harvest of 2-year-old females, which have high reproductive
      potential.

PMID- 21073456
TI  - Editorial: Early prevention and intervention--the five W (and one H) questions.

PMID- 21073457
TI  - Brief parent training in pivotal response treatment for preschoolers with autism.
AB  - BACKGROUND: Evidence of improved outcomes with early behavioural intervention has
      placed the early treatment of autism as a health priority. However, long waiting
      lists for treatment often preclude timely access, raising the question of whether
      parents could be trained in the interim. Parent training in pivotal response
      treatment (PRT) has been shown to enhance the communication skills of children
      with autism. This is typically provided within a 25-hour programme, although less
      intensive parent training may also be effective. The main objective of the
      present study was to evaluate the efficacy of brief training in PRT for parents
      of preschoolers with autism, who were awaiting, or unable to access, more
      comprehensive treatment. METHOD: Eight preschoolers with autism and their parents
      participated in the study. A non-concurrent multiple (across-participants)
      baseline design was used, in which parents were seen individually for three 2
      hour training sessions on PRT. Child and parent outcomes were assessed before,
      immediately after, and 2 to 4 months following training using standardised tests,
      questionnaires and behaviour coded directly from video recordings. RESULTS:
      Overall, children's communication skills, namely functional utterances, increased
      following training. Parents' fidelity in implementing PRT techniques also
      improved after training, and generally these changes were maintained at follow
      up. A moderate to strong relationship was found between parents' increased
      ability to implement PRT techniques and improvement in the children's
      communication skills. CONCLUSION: Our findings suggest that brief parent training
      in PRT promises to provide an immediate, cost-effective intervention that could
      be adopted widely.

PMID- 21073459
TI  - Perceptions of social conflicts among incarcerated adolescents with callous
      unemotional traits: 'you're going to pay. It's going to hurt, but I don't care.'.
AB  - BACKGROUND: Delinquent youth with callous-unemotional (CU) traits may have a
      unique social-cognitive processing pattern that perpetuates their violent
      behavior. The current study examined the association between CU traits and the
      endorsement of deviant social goals during peer conflicts as well as expectancies
      and values regarding victim suffering following aggression. METHODS: Participants
      included 156 (84 males, 72 females) adjudicated juveniles residing at two gender
      specific residential facilities in an urban city within the southeastern United
      States. The association between CU traits and participants' ratings of their
      social goals in hypothetic conflict situations and outcome expectancies/values
      regarding victim suffering were examined after controlling for prior violence,
      intelligence, and demographic covariates. RESULTS:  CU traits were associated
      with an increased endorsement of social goals associated with revenge, dominance,
      and forced respect in social conflict situations. Adjudicated youth with CU
      traits were also less likely to endorse conflict avoidance and friendship
      building as important social goals when provoked by peers. There was no
      association between CU traits and expectations for victim suffering following
      aggression, but CU traits were significantly associated with lower levels of
      concern about victim suffering. These findings were significant after controlling
      for participants' prior history of violence, intelligence, and demographic
      covariates. CONCLUSIONS: Adjudicated youth with CU traits tend to emphasize power
      oriented goals when provoked by peers and have little interest in rectifying
      social conflicts to build potential friendships with others. Juveniles with CU
      traits seem to be aware that their aggressive behavior will cause others to
      suffer, but they do not care when it does.

PMID- 21073460
TI  - Pituitary volume prospectively predicts internalizing symptoms in adolescence.
AB  - BACKGROUND: Early adolescence is a critical time for the development of both
      internalizing and externalizing disorders. We aimed to investigate whether
      pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function,
      represents a vulnerability factor for the emergence of internalizing and
      externalizing symptoms during adolescence using a prospective, longitudinal
      design. METHODS: One hundred and fifty-five adolescents completed 3T structural
      magnetic resonance imaging (MRI), symptom rating scales and a diagnostic
      interview during early adolescence (M age 12.6 years, SD .5 years); symptom
      rating scales were re-administered approximately three years later (M age 15.2
      years). The volume of the pituitary gland was estimated by manually delineating
      its structure on MR images. The degree to which pituitary volumes prospectively
      predicted change in internalizing and externalizing symptoms across the two time
      points was assessed using hierarchal linear regression, after controlling for the
      influence of gender, age, pubertal stage and intracranial volume. RESULTS: Larger
      pituitary volumes prospectively predicted an increase in internalizing, but not
      externalizing, symptoms from early adolescence to mid-adolescence. CONCLUSIONS:
      This study provides the first evidence that increased pituitary volume might
      represent a specific vulnerability marker for the development of internalizing
      symptoms during early to mid-adolescence.

PMID- 21073458
TI  - Task-related default mode network modulation and inhibitory control in ADHD:
      effects of motivation and methylphenidate.
AB  - BACKGROUND: Deficits characteristic of attention deficit/hyperactivity disorder
      (ADHD), including poor attention and inhibitory control, are at least partially
      alleviated by factors that increase engagement of attention, suggesting a
      hypodopaminergic reward deficit. Lapses of attention are associated with
      attenuated deactivation of the default mode network (DMN), a distributed brain
      system normally deactivated during tasks requiring attention to the external
      world. Task-related DMN deactivation has been shown to be attenuated in ADHD
      relative to controls. We hypothesised that motivational incentives to balance
      speed against restraint would increase task engagement during an inhibitory
      control task, enhancing DMN deactivation in ADHD. We also hypothesised that
      methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal
      patterns of DMN deactivation. METHOD: We obtained functional magnetic resonance
      images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined
      subtype) and 18 pairwise-matched typically developing children aged 9-15 years
      while they performed a paced Go/No-go task. We manipulated motivational incentive
      to balance response speed against inhibitory control, and tested children with
      ADHD both on and off methylphenidate. RESULTS: When children with ADHD were off
      methylphenidate and task incentive was low, event-related DMN deactivation was
      significantly attenuated compared to controls, but the two groups did not differ
      under high motivational incentives. The modulation of DMN deactivation by
      incentive in the children with ADHD, off-methylphenidate, was statistically
      significant, and significantly greater than in typically developing children.
      When children with ADHD were on-methylphenidate, motivational modulation of event
      related DMN deactivation was abolished, and no attenuation relative to their
      typically developing peers was apparent in either motivational condition.
      CONCLUSIONS: During an inhibitory control task, children with ADHD exhibit a
      raised motivational threshold at which task-relevant stimuli become sufficiently
      salient to deactivate the DMN. Treatment with methylphenidate normalises this
      threshold, rendering their pattern of task-related DMN deactivation
      indistinguishable from that of typically developing children.

PMID- 21073461
TI  - Auditory conflict processing in ADHD.
AB  - BACKGROUND: Impaired cognitive control has been implicated as an important
      developmental pathway to attention deficit/hyperactivity disorder (ADHD).
      Cognitive control is crucial to suppress interference resulting from conflicting
      information and can be measured by Stroop-like tasks. This study was conducted to
      gain insight into conflict processing in children with ADHD. METHODS: Event
      related potentials (ERPs) were recorded in an auditory Stroop task. Twenty-four
      children with ADHD were compared with 24 control children (aged 8-12 years).
      RESULTS: No deficit in interference control was found on the auditory Stroop task
      in children with ADHD. Children with ADHD responded more slowly, less accurately
      and more variably compared to controls. No differences between the groups
      occurred in the early conflict-related ERPs. However, the difference between the
      congruent and the incongruent condition in the 450-550 ms time window was absent
      in the ADHD group compared to controls. In addition, the conflict sustained
      potential was found frontally in the ADHD group but parietally in the control
      group. CONCLUSIONS: These ERP findings suggest that children with ADHD evaluate
      conflict to a lesser extent and differ in the way their brains select appropriate
      responses during conflict compared with controls.

PMID- 21073462
TI  - The nature of trauma memories in acute stress disorder in children and
      adolescents.
AB  - BACKGROUND: There is increasing theoretical, clinical and research evidence for
      the role of trauma memory in the aetiology of acute pathological stress responses
      in adults. However, research into the phenomenology of trauma memories in young
      people is currently scarce. METHODS: This study compared the nature of trauma
      narratives to narratives of unpleasant non-traumatic events in young people (aged
      8-17) who sought emergency medical attention following an assault or road traffic
      accident. Data were collected within 2-4 weeks of the index event. Symptom
      severity was assessed by child self-report and face-to-face diagnostic
      interviews. Comparisons of narrative indices were made between those children
      with acute stress disorder (ASD) and those without ASD. RESULTS: Among
      participants (n = 50), those with ASD (38%) had significantly elevated levels of
      disorganisation in their trauma narrative, compared both to trauma-exposed
      controls and to their unpleasant comparative narrative. This effect was not
      accounted for by age. Regardless of ASD diagnostic status, trauma narratives had
      significantly higher sensory content and significantly lower positive emotion
      content compared to the unpleasant comparative narrative. These effects were not
      significant when age was included as a covariate. Acute symptom severity was
      significantly predicted by the level of disorganisation in the trauma narrative
      and the child's cognitive appraisals of the event. CONCLUSIONS: These data
      provide the first empirical evidence that disorganisation is not only directly
      linked to symptom severity, but also specific to the trauma memory. In addition,
      it provides support for the adaptation of adult cognitive models to acute
      pathological stress reactions in children and adolescents.

PMID- 21073463
TI  - Maternal eating disorders and infant feeding difficulties: maternal and child
      mediators in a longitudinal general population study.
AB  - BACKGROUND: Maternal eating disorders (ED) have been shown to increase the risk
      of feeding difficulties in the offspring. Very few studies, however, have
      investigated whether the effect of a maternal ED on childhood feeding is a direct
      effect or whether it can be ascribed to other child or maternal factors. We aimed
      to determine the role of maternal anxiety and depression in mediating the risk
      for feeding difficulties in infants of women with ED. METHODS: A prospective
      study comparing women with lifetime ED (441) and without any lifetime psychiatric
      disorder (10,461) and their infants from the Avon Longitudinal Study of Parents
      and Children (ALSPAC). We investigated the effect of: maternal anxiety and
      depression in late pregnancy (32 weeks) and the post-partum (8 weeks), child
      temperament and developmental status on infant feeding difficulties at 1 and 6
      months. We also investigated the effect of active pregnancy ED symptoms. We
      tested 3 models and their fit to the data using structured equation modelling: a
      direct effect model, a fully mediational model and an integrated (partial
      meditational) model. RESULTS: The integrated model including a direct effect of
      maternal lifetime ED on infant feeding and a mediational path via maternal
      distress (a latent variable combining anxiety and depression) fitted the data
      best. This also applied to maternal pregnancy ED symptoms. Feeding difficulties
      in turn increased maternal distress over time. CONCLUSIONS: Lifetime ED and
      active pregnancy ED increase the risk for infant feeding difficulties and do so
      via maternal distress (i.e., depression and anxiety). This has important
      implications for prevention and early intervention in relation to infant feeding
      difficulties, as well as for future research in the field.

PMID- 21073464
TI  - Tract-specific analyses of diffusion tensor imaging show widespread white matter
      compromise in autism spectrum disorder.
AB  - BACKGROUND: Previous diffusion tensor imaging (DTI) studies have shown white
      matter compromise in children and adults with autism spectrum disorder (ASD),
      which may relate to reduced connectivity and impaired function of distributed
      networks. However, tract-specific evidence remains limited in ASD. We applied
      tract-based spatial statistics (TBSS) for an unbiased whole-brain quantitative
      estimation of the fractional anisotropy (FA), mean diffusion (MD) and axial and
      radial diffusion of the white matter tracts in children and adolescents with ASD.
      METHODS: DTI was performed in 26 ASD and 24 typically developing (TD)
      participants, aged 9-20 years. Groups were matched for age and IQ. Each
      participant's aligned FA, MD and axial and radial diffusion data were projected
      onto the mean FA skeleton representing the centers of all tracts and the
      resulting data fed into voxelwise group statistics. RESULTS: TBSS revealed
      decreased FA and increased MD and radial diffusion in the ASD group compared to
      the TD group in the corpus callosum, anterior and posterior limbs of the internal
      capsule, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus,
      superior longitudinal fasciculus, cingulum, anterior thalamic radiation, and
      corticospinal tract. No single site with inverse effects (increased FA, reduced
      MD or radial diffusion in the ASD group) was detected. In clusters of significant
      group difference, age was positively correlated with FA and negatively correlated
      with MD and radial diffusion in the TD, but not the ASD group. CONCLUSIONS: Our
      findings reveal white matter compromise affecting numerous tracts in children and
      adolescents with ASD. Slightly varying patterns of diffusion abnormalities
      detected for some tracts may suggest tract-specific patterns of white matter
      abnormalities associated with ASD. Age-dependent effects further show that
      maturational changes (increasing FA, decreasing MD and radial diffusion with age)
      are diminished in ASD from school-age childhood into young adulthood.

PMID- 21073465
TI  - Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant.
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent
      known cause of autosomal dominant Parkinson's disease. The LRRK2 gene encodes a
      Roco protein featuring a Ras of complex proteins (ROC) GTPase and a kinase domain
      linked by the C-terminal of ROC (COR) domain. Here, we explored the effects of
      the Y1699C pathogenic LRRK2 mutation in the COR domain on GTPase activity and
      interactions within the catalytic core of LRRK2. We observed a decrease in GTPase
      activity for LRRK2 Y1699C comparable to the decrease observed for the R1441C
      pathogenic mutant and the T1348N dysfunctional mutant. To study the underlying
      mechanism, we explored the dimerization in the catalytic core of LRRK2. ROC-COR
      dimerization was significantly weakened by the Y1699C or R1441C/G mutation. Using
      a competition assay, we demonstrated that the intra-molecular ROC : COR
      interaction is favoured over ROC : ROC dimerization. Interestingly, the intra
      molecular ROC : COR interaction was strengthened by the Y1699C mutation. This is
      supported by a 3D homology model of the ROC-COR tandem of LRRK2, showing that
      Y1699 is positioned at the intra-molecular ROC : COR interface. In conclusion,
      our data provides mechanistic insight into the mode of action of the Y1699C LRRK2
      mutant: the Y1699C substitution, situated at the intra-molecular ROC : COR
      interface, strengthens the intra-molecular ROC : COR interaction, thereby locally
      weakening the dimerization of LRRK2 at the ROC-COR tandem domain resulting in
      decreased GTPase activity.

PMID- 21073466
TI  - Regulation of dopaminergic neuron firing by heterogeneous dopamine autoreceptors
      in the substantia nigra pars compacta.
AB  - Dopamine (DA) receptors generate many cellular signals and play various roles in
      locomotion, motivation, hormone production, and drug abuse. According to the
      location and expression types of the receptors in the brain, DA signals act in
      either stimulatory or inhibitory manners. Although DA autoreceptors in the
      substantia nigra pars compacta are known to regulate firing activity, the exact
      expression patterns and roles of DA autoreceptor types on the firing activity are
      highly debated. Therefore, we performed individual correlation studies between
      firing activity and receptor expression patterns using acutely isolated rat
      substantia nigra pars compacta DA neurons. When we performed single-cell RT-PCR
      experiments, D(1), D(2)S, D(2)L, D(3), and D(5) receptor mRNA were
      heterogeneously expressed in the order of D(2)L > D(2)S > D(3) > D(5) > D(1).
      Stimulation of D(2) receptors with quinpirole suppressed spontaneous firing
      similarly among all neurons expressing mRNA solely for D(2)S, D(2)L, or D(3)
      receptors. However, quinpirole most strongly suppressed spontaneous firing in the
      neurons expressing mRNA for both D(2) and D(3) receptors. These data suggest that
      D(2) S, D(2)L, and D(3) receptors are able to equally suppress firing activity,
      but that D(2) and D(3) receptors synergistically suppress firing. This diversity
      in DA autoreceptors could explain the various actions of DA in the brain.

PMID- 21073467
TI  - The immediately releasable vesicle pool: highly coupled secretion in chromaffin
      and other neuroendocrine cells.
AB  - In neuroendocrine cells, such as adrenal chromaffin cells, the exocytosis of
      hormone-filled vesicles is triggered by a localized Ca(2+) increase that develops
      after the activation of voltage-dependent Ca(2+) channels. To reach the fusion
      competent state, vesicles have to go through a series of maturation steps that
      involve the detachment from cytoskeletal proteins, docking and priming. However,
      the fusion readiness of vesicles will also depend on their proximity to the
      calcium source. The immediately releasable pool is a small group of ready-to-fuse
      vesicles, whose fusion is tightly coupled to Ca(2+) entry through channels.
      Recent work indicates that such coupling is not produced by a random distribution
      between vesicles and channels, but would be the result of a specific interaction
      of immediately releasable vesicles with particular Ca(2+) channel subtypes. The
      immediately releasable pool is able to sustain, with high efficiency, the
      secretion triggered by the small and localized Ca(2+) gradients produced by brief
      depolarizations at low frequencies, like action potentials at basal conditions in
      adrenal chromaffin cells.

PMID- 21073469
TI  - Regulation of nonsymbiotic and truncated hemoglobin genes of Lotus japonicus in
      plant organs and in response to nitric oxide and hormones.
AB  - * In legumes, symbiotic leghemoglobins facilitate oxygen diffusion to the
      bacteroids, but the roles of nonsymbiotic and truncated hemoglobins are largely
      unknown. Here the five hemoglobin genes of Lotus japonicus have been functionally
      characterized to gain insight into their regulatory mechanisms. * Plants were
      exposed to nitric oxide donors, stressful conditions, and hormones. Gene
      expression profiling was determined by quantitative PCR, and gene activities were
      localized using in situ hybridization and promoter-reporter gene fusions. * The
      LjGLB1-1, LjGLB2, and LjGLB3-1 mRNA expression levels were very high in nodules
      relative to other plant organs. The expression of these genes was localized in
      the vascular bundles, cortex, and infected tissue. LjGLB1-1 was the only gene
      induced by nitric oxide. Cytokinins caused nearly complete inactivation of LjGLB2
      and LjGLB3-1 in nodules and induction of LjGLB1-1 in roots. Abscisic acid induced
      LjGLB1-1 in nodules and LjGLB1-2 and LjGLB2 in roots, whereas polyamines and
      jasmonic acid induced LjGLB1-1 only in roots. * The enhanced expression of the
      three types of hemoglobins in nodules, the colocalization of gene activities in
      nodule and root tissues with high metabolic rates, and their distinct regulatory
      mechanisms point out complementary roles of hemoglobins and strongly support the
      hypothesis that LjGLB1-1, LjGLB2, and LjGLB3-1 are required for symbiosis.

PMID- 21073468
TI  - The emerging role of trace amine-associated receptor 1 in the functional
      regulation of monoamine transporters and dopaminergic activity.
AB  - It is now recognized that trace amine associated-receptor 1 (TAAR1) plays a
      functional role in the regulation of brain monoamines and the mediation of action
      of amphetamine-like psychostimulants. Accordingly, research on TAAR1 opens the
      door to a new avenue of approach for medications development to treat drug
      addiction as well as the spectrum of neuropsychiatric disorders hallmarked by
      aberrant regulation of brain monoamines. This overview focuses on recent studies
      which reveal a role for TAAR1 in the functional regulation of monoamine
      transporters and the neuronal regulatory mechanisms that modulate dopaminergic
      activity.

PMID- 21073470
TI  - Ultraviolet-C irradiation for prevention of central venous catheter-related
      infections: an in vitro study.
AB  - Central venous catheters (CVC) are widely used in the United States and are
      associated with 250,000 to 500,000 CVC-related infections in hospitals annually.
      We used a catheter made from ultraviolet-C (UVC) transmissive material to test
      whether delivery of UVC from the lumen would allow inactivation of microorganisms
      on the outer surface of CVC. When the catheter was exposed to UVC irradiation
      from a cold cathode fluorescent lamp inside the catheter lumen at a radiant
      exposure of 3.6 mJ cm(-2) , more than 6-log(10) of drug-resistant Gram-positive
      bacteria adhered to the outer surface of the catheter were inactivated. Three to
      7-log(10) of drug-resistant Gram-negative bacteria and 2.80-log(10) of fungi were
      inactivated at a radiant exposure of 11 mJ cm(-2).UVC irradiation also offered a
      highly selective inactivation of bacteria over keratinocytes under exactly
      comparable conditions. After 11 mJ cm(-2) UVC light had been delivered, over 6
      log(10) of bacteria were inactivated while the viability loss of the
      keratinocytes was only about 57%.

PMID- 21073471
TI  - Effect of laser and LED on enzymatic production of ceramide.
AB  - An enzyme (Phospholipase C Type I from Clostridium perfringens) was exposed to 0
      810Jcm(-2) of energy using laser light at wavelengths 808, 532, 1064 and 1342nm
      and two LED light sources at wavelengths 810 and 640nm. Enzyme responses were
      evaluated by measuring ceramide concentration using high performance thin-layer
      chromatography (HPTLC) at 0.5, 1, 2, 3, 4, 6, 17, 24h after irradiation. The
      duration of effect was evaluated from the experimental data. The results show
      that enzyme activity can be increased by using both laser and LED sources whose
      wavelength is located within a certain range. The effect depends on the energy
      and wavelength of the light. The increase in enzyme activity continued for about
      4h after irradiation. This study shows that the duration of irradiation should be
      included as one of the main laser parameters when reporting on the effects of
      laser irradiation on enzymes. We also find that laser sources and LED sources
      have the same effect on enzyme activity if the wavelength and absorbed energy are
      equal.

PMID- 21073472
TI  - Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I
      meningioma cells corresponds to ferrochelatase activity.
AB  - 5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX),
      which can be used as a photosensitizer in photodynamic therapy (PDT).
      Accumulation of PpIX in benign meningioma cells has been observed previously, its
      exploitation for PDT, however, was discouraged by inconsistent results. To
      evaluate PDT for benign meningiomas, we investigated PpIX synthesis in two human
      meningioma cell lines (HBL-52 and BEN-MEN-1), their respective extracellular loss
      of PpIX and corresponding ferrochelatase (FECH) activity as well as their
      susceptibility to PDT. We demonstrated PpIX production after 5-ALA administration
      and minor loss to the extracellular space in both cell lines. However,
      significantly more (up to five times) PpIX was accumulated in BEN-MEN-1 as
      compared with HBL-52 cells. FECH activity was 2.7-fold higher in HBL-52 compared
      with BEN-MEN-1 cells and accordingly higher FECH levels could be shown in HBL-52
      cells by Western blot analysis. BEN-MEN-1 cells were much more sensitive to PDT
      and cells could be almost completely killed by irradiation doses of 2 J cm(-2) ,
      whereas HBL-52 showed only an insufficient response at this irradiation dose. We
      conclude that differences in intracellular PpIX concentrations between HBL-52 and
      BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity
      and that these differences correspond to their susceptibility to 5-ALA-induced
      PDT.

PMID- 21073473
TI  - Acetate versus sulfur deprivation role in creating anaerobiosis in light for
      hydrogen production by Chlamydomonas reinhardtii and Spirulina platensis: two
      different organisms and two different mechanisms.
AB  - This work was devoted to separate acetate role in creating anaerobiosis from that
      of sulfur deprivation. Chlamydomonas reinhardtii grown in TAP (Tris-acetate
      phosphate) medium was resuspended in sulfur-replete or -deprived medium in sealed
      or nonsealed cultures. Sulfur deprivation was substantial for starch accumulation
      and hydrogen evolution; however, acetate induced anaerobiosis in the presence or
      absence of sulfur in only sealed cultures. In nonsealed cultures, Chlamydomonas
      did not lose its photosynthetic activity; however, it was arrested in anoxia with
      no photosynthetic activity as long as the culture was sealed. The sealed cultures
      resumed photosynthesis upon unsealing overnight unless the cells died by anoxia
      at late stage of the experiment. These results indicate that the enhanced oxygen
      consumption for the enormous acetate respiration and inhibition of the external
      oxygen supply in sealed cultures of Chlamydomonas are the main reasons for the
      steady anaerobic conditions. Although acetate was substantial for creating
      anaerobiosis in Chlamydomonas, sulfur deprivation alone could create anaerobiosis
      in Spirulina platensis grown autotrophically. Hydrogen evolution and glycogen
      accumulation were induced under such conditions. Severely reduced phycocyanin,
      chlorophyll and photosynthesis, while respiration had increased, induced
      anaerobiosis in Spirulina. This study reports for the first time anaerobiosis
      under autotrophic conditions in a cyanobacterium.

PMID- 21073474
TI  - Ultraviolet-A irradiation to the eye modulates intestinal mucosal functions and
      properties of mast cells in the mouse.
AB  - We previously reported that topical irradiation of the eye by ultraviolet-B (UVB)
      activated hypothalamo-pituitary-adrenal axis (HPA-A) of the mouse to increase 3,
      4-dihydroxyphenylalanine (DOPA)-positive melanocytes in the skin by an inducible
      nitric oxide synthase (iNOS)-dependent mechanism. This work demonstrates that
      irradiation of the eye by ultraviolet-A (UVA) specifically increased DOPA
      positive cells in the mucosa of the jejunum and colon of C57BL/6J mice by some
      HPA- and iNOS-independent mechanism. UVA-induced increase in DOPA-positive cells
      in the intestine was inhibited by the administration of hexamethonium or prazosin
      plus propranolol, blockers for the sympathetic nervous system. UVA irradiation of
      the eye increased DOPA- and histidine decarboxylase (HDC)-positive cells in the
      intestinal mucosa of both C57BL/6J and WBB6F1/J mice but not in the mutant strain
      W/Wv of the latter that lack mast cells. UVA irradiation of the eye suppressed
      the intestinal peristalsis of control, hypophysectomized or iNOS(-/-) C57BL/6J
      mice by the mechanism that was inhibited by hexamethonium or prazosin plus
      propranolol. These observations suggest that UVA irradiation of the eye
      stimulated the sympathetic nervous system to increase the mucosal DOPA- and HDC
      positive mast cells and suppressed the peristalsis of the small intestine of the
      mouse.

PMID- 21073475
TI  - Influence of variation in eumelanin content on absorbance spectra of liquid skin
      like phantoms.
AB  - The attenuation behavior of two different types of skin-like phantoms
      representing the range of Fitzpatrick skin Types I-VI was investigated and
      compared with real human skin. Intralipid (IL) and Pheroid(TM) artificial lipid
      membrane vesicles, respectively, were added to synthetic eumelanin concentrations
      ranging from 0.0044 to 0.13mgmL(-1) to produce skin-like phantoms.
      Spectrophotometric absorbance and transmittance measurements were performed.
      Results indicated some of the nonmonotonic trends observed in real human skin,
      albeit shifted more toward the visible wavelength range. There exists, however,
      an underlying difference in interaction between the melanin and the Pheroid(TM)
      and IL skin-like phantoms.

PMID- 21073476
TI  - DNA photo-oxidative damage hazard in transfection complexes.
AB  - Complexes of DNA with various cationic vectors have been largely used for
      nonviral transfection, and yet the photochemical stability of DNA in such
      complexes has never been considered. We studied, for the first time, the
      influence of DNA complexation by a cationic lipid and polymers on the amount of
      damage induced by benzophenone photosensitization. The localization of
      benzophenone inside the hydrophobic domains formed by a cationic lipid, DOTAP (N
      [1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride), and close to DNA,
      locally increases the photoinduced cleavage by the reactive oxygen species
      generated. The same effect was found in the case of DNA complexation with an
      amphiphilic polymer (polynorbornenemethyleneammonium chloride). However, a
      decrease in DNA damage was observed in the case of complexation with a
      hydrophilic polymer (polyethylenimine). The DNA protection in this case was
      because of the absence of benzophenone hydrophobic incorporation into the
      complex, and to DNA compaction which decreased the probability of radical attack.
      These results underline the importance of the chemical structure of the nonviral
      transfection vector in limiting the risks of photo-oxidative damage of the
      complexed DNA.

PMID- 21073477
TI  - Photoinduced superoxide radical anion and singlet oxygen generation in the
      presence of novel selenadiazoloquinolones (an EPR Study).
AB  - Novel 7-substituted 6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline (SeQ(1
      6)) and 8-substituted 9-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-f ]quinoline
      derivatives (SeQN(1-5)) with R(7), R(8) =H, COOC(2) H(5), COOCH(3), COOH, COCH(3)
      or CN were synthesized and their spectral characteristics were obtained by UV/Vis
      spectroscopy. Ultraviolet A photoexcitation of the selenadiazoloquinolones in
      dimethylsulfoxide or acetonitrile resulted in the formation of paramagnetic
      species coupled with molecular oxygen activation generating the superoxide
      radical anion or singlet oxygen, evidenced by electron paramagnetic resonance
      spectroscopy. The cytotoxic/photocytotoxic impact of selenadiazoloquinolones on
      murine and human cancer cell lines was demonstrated using the derivative SeQ5
      (with R(7)=COCH(3)).

PMID- 21073478
TI  - Photodimerization of 7,8-dihydroneopterin in aqueous solution under UV-A
      irradiation.
AB  - 7,8-Dihydroneopterin (H(2) Nep) is secreted during the oxidative burst of
      stimulated macrophages. The photochemistry of H(2) Nep was investigated in
      neutral aqueous solutions exposed to UV-A radiation (320-400nm) at room
      temperature. The kinetics were followed by UV/Vis spectrophotometry and HPLC,
      whereas the photoproducts were analyzed by electrospray ionization mass
      spectrometry. Excitation of H(2) Nep leads to the formation of isomeric dimers
      with molecular masses equal to exactly twice the molecular mass of the reactant.
      The corresponding quantum yield of H(2) Nep consumption (Phi(-R) =(3.8+/-0.5)*10(
      2)) was independent of O(2) and reactant concentrations. Mechanistic implications
      are discussed.

PMID- 21073479
TI  - Electrocortical evidence for vigilance-avoidance in Generalized Anxiety Disorder.
AB  - Both exaggerated and attenuated responses to emotional stimuli have been
      documented in Generalized Anxiety Disorder (GAD). Event-related potentials are
      well-suited for examining the time-course of neural activity during emotional
      processing; early components (e.g., the P1) appear to index relatively automatic
      attention to emotional stimuli, whereas later positivities (e.g., the late
      positive potential or LPP) index dynamic allocation of attention to emotional
      stimuli. Twenty-one individuals with GAD and 25 healthy controls (HC) passively
      viewed emotional and neutral images while ERPs were recorded. An enhanced P1 for
      unpleasant compared to neutral images was larger in GAD. In addition, the
      increased LPP to unpleasant compared to neutral images was diminished in the GAD
      group. These data provide evidence for early hypervigilance for emotional
      stimuli, followed by failure to engage in elaborative processing, in GAD.

PMID- 21073480
TI  - Interoceptive threat leads to defensive mobilization in highly anxiety sensitive
      persons.
AB  - To study defensive mobilization elicited by the exposure to interoceptive arousal
      sensations, we exposed highly anxiety sensitive students to a symptom provocation
      task. Symptom reports, autonomic arousal, and the startle eyeblink response were
      monitored during guided hyperventilation and a recovery period in 26 highly
      anxiety sensitive persons and 22 controls. Normoventilation was used as a non
      provocative comparison condition. Hyperventilation led to autonomic arousal and a
      marked increase in somatic symptoms. While high and low anxiety sensitive persons
      did not differ in their defensive activation during hyperventilation, group
      differences were detected during early recovery. Highly anxiety sensitive
      students exhibited a potentiation of startle response magnitudes and increased
      autonomic arousal after hyper- as compared to after normoventilation, indicating
      defensive mobilization evoked by the prolonged presence of feared somatic
      sensations.

PMID- 21073481
TI  - The N400 and the P300 are not all that independent.
AB  - This study assessed whether two ERP components that are elicited by unexpected
      events interact. The conditions that are known to elicit the N400 and the P300
      ERP components were applied separately and in combination to terminal-words in
      sentences. Each sentence ended with a terminal-word that was highly expected,
      semantically unexpected, physically deviant, or both semantically unexpected and
      physically deviant. In addition, we varied the level of semantic relatedness
      between the unexpected terminal-words and the expected exemplars. Physically
      deviant words elicited a P300, whereas semantically unexpected words elicited an
      N400, whose amplitude was sensitive to the level of semantic relatedness. Words
      that were both semantically unexpected and physically deviant elicited both an
      N400 with enhanced amplitude, and a P300 with reduced amplitude. These results
      suggest an interaction between the processes manifested by the two components.

PMID- 21073482
TI  - The effect of lysophosphatidic acid and Rho-associated kinase patterning on
      adhesion of dental pulp cells.
AB  - AIM: To investigate the effects of lysophosphatidic acid (LPA) and the Rho/Rho
      associated kinase (ROCK) pathway on adhesion of dental pulp cells (DPCs).
      METHODOLOGY: Human DPCs were cultured ex vivo. After treatment of LPA and Y
      27632, a specific ROCK inhibitor, changes in focal contacts (FCs) were examined
      by immunofluorescent staining. Activation of FCs proteins was examined by
      measuring tyrosine 397 phosphorylation of focal adhesion kinase (FAK) and
      paxillin using immunoblotting. The data were analysed by Student's t-test.
      RESULTS: The immunofluorescent staining indicated LPA stimulation induced larger
      focal adhesion in the cell periphery, compared with the control. Inhibition of
      ROCK by Y-27632 decreased the formation of FCs markedly, even in the LPA
      stimulated cells. LPA also increased the level of tyrosine phosphorylation of
      paxillin at 30min (P<0.05) and FAK at 5 and 30min (P<0.05). Furthermore, p
      paxillin levels declined immediately after Y-27632 treatment and remained low at
      5, 30, 60min. Y-27632 also suppressed the effects of LPA on p-paxillin and p-FAK
      at 5 and 30min (P<0.05). CONCLUSION: LPA activated Rho and then subsequently
      activated ROCK, suggesting that LPA influences the FCs of DPCs by modulating
      tyrosine phosphorylation of FAK and paxillin via the Rho/ROCK pathway.

PMID- 21073483
TI  - Adolescents at risk for alcohol abuse demonstrate altered frontal lobe activation
      during Stroop performance.
AB  - BACKGROUND: Children and adolescents, family history positive (FH+) for
      alcoholism, exhibit differences in brain structure and functional activation when
      compared to family history negative (FH-) counterparts. Given that frontal brain
      regions, and associated reciprocal connections with limbic structures, undergo
      the most dramatic maturational changes during adolescence, the objective of this
      study was to compare functional brain activation during a frontally mediated test
      of response inhibition in 32 adolescents separated into low-risk (FH-) and high
      risk (FH+) groups. METHODS: Functional magnetic resonance (fMRI) blood oxygen
      level-dependent data were acquired at 1.5 Tesla during performance of Stroop
      Color Naming, Word Reading, and Interference. Preprocessing and statistical
      analyses, covaried for age, were conducted in SPM99 using a search territory that
      included superior, middle, and inferior frontal gyri (trigone region), anterior
      cingulate gyrus (CG), and left and right amygdala. RESULTS: Significantly greater
      activation in the fronto-limbic search territory was observed in FH+ relative to
      FH- subjects during Stroop Interference. In addition, a significant regression
      between brain activation and family history density was observed, with a greater
      density being associated with increased activation in regions including middle
      frontal gyrus (BA9) and CG (BA24). CONCLUSIONS: These data demonstrate a
      significant influence of FH status on brain activation during the performance of
      a response inhibition task, perhaps reflecting a neurobiological vulnerability
      associated with FH status that may include reduced neuronal efficiency and/or
      recruitment of additional neuronal resources. These findings are important given
      that the adolescent developmental period is already associated with reduced
      inhibitory capacity, even prior to the onset of alcohol use.

PMID- 21073484
TI  - Impaired delay and trace eyeblink conditioning in school-age children with fetal
      alcohol syndrome.
AB  - BACKGROUND: Classical eyeblink conditioning (EBC) involves contingent temporal
      pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus
      (e.g., air puff). Impairment of EBC has been demonstrated in studies of alcohol
      exposed animals and in children exposed prenatally at heavy levels. METHODS:
      Fetal alcohol syndrome (FAS) was diagnosed by expert dysmorphologists in a large
      sample of Cape Coloured, South African children. Delay EBC was examined in a new
      sample of 63 children at 11.3 years, and trace conditioning in 32 of the same
      children at 12.8 years. At each age, 2 sessions of 50 trials each were
      administered on the same day; 2 more sessions the next day, for children not
      meeting criterion for conditioning. RESULTS: Six of 34 (17.6%) children born to
      heavy drinkers were diagnosed with FAS, 28 were heavily exposed nonsyndromal
      (HE), and 29 were nonexposed controls. Only 33.3% with FAS and 42.9% of HE met
      criterion for delay conditioning, compared with 79.3% of controls. The more
      difficult trace conditioning task was also highly sensitive to fetal alcohol
      exposure. Only 16.7% of the FAS and 21.4% of HE met criterion for trace
      conditioning, compared with 66.7% of controls. The magnitude of the effect of
      diagnostic group on trace conditioning was not greater than the effect on short
      delay conditioning, findings consistent with recent rat studies. Longer latency
      to onset and peak eyeblink CR in exposed children indicated poor timing and
      failure to blink in anticipation of the puff. Extended training resulted in some
      but not all of the children reaching criterion. CONCLUSIONS: These data showing
      alcohol-related delay and trace conditioning deficits extend our earlier findings
      of impaired EBC in 5-year-olds to school-age. Alcohol-related impairment in the
      cerebellar circuitry required for both forms of conditioning may be sufficient to
      account for the deficit in both tasks. Extended training was beneficial for some
      exposed children. EBC provides a well-characterized model system for assessment
      of degree of cerebellar-related learning and memory dysfunction in fetal alcohol
      exposed children.

PMID- 21073486
TI  - Energy drink consumption and increased risk for alcohol dependence.
AB  - BACKGROUND: Energy drinks are highly caffeinated beverages that are increasingly
      consumed by young adults. Prior research has established associations between
      energy drink use and heavier drinking and alcohol-related problems among college
      students. This study investigated the extent to which energy drink use might pose
      additional risk for alcohol dependence over and above that from known risk
      factors. METHODS: Data were collected via personal interview from 1,097 fourth
      year college students sampled from 1 large public university as part of an
      ongoing longitudinal study. Alcohol dependence was assessed according to DSM-IV
      criteria. RESULTS: After adjustment for the sampling design, 51.3%(wt) of
      students were classified as "low-frequency" energy drink users (1 to 51 days in
      the past year) and 10.1%(wt) as "high-frequency" users (>=52 days). Typical
      caffeine consumption varied widely depending on the brand consumed. Compared to
      the low-frequency group, high-frequency users drank alcohol more frequently
      (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical
      drinking day). High-frequency users were at significantly greater risk for
      alcohol dependence relative to both nonusers (AOR = 2.40, 95% CI = 1.27 to 4.56,
      p = 0.007) and low-frequency users (AOR = 1.86, 95% CI = 1.10, 3.14, p = 0.020),
      even after holding constant demographics, typical alcohol consumption,
      fraternity/sorority involvement, depressive symptoms, parental history of
      alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink
      users did not differ from nonusers on their risk for alcohol dependence.
      CONCLUSIONS: Weekly or daily energy drink consumption is strongly associated with
      alcohol dependence. Further research is warranted to understand the possible
      mechanisms underlying this association. College students who frequently consume
      energy drinks represent an important target population for alcohol prevention.

PMID- 21073485
TI  - Associations between heavy drinking and changes in impulsive behavior among
      adolescent boys.
AB  - BACKGROUND: Impulsive behavior in humans predicts the onset of drinking during
      adolescence and alcohol use disorders (AUDs) in adulthood. It is also possible,
      however, that heavy drinking may increase impulsive behavior by affecting the
      development of brain areas that support behavioral control or through other
      associated mechanisms. This study examined whether drinking heavily during
      adolescence is related to changes in impulsive behavior with a specific focus on
      how the association differs across individuals, contingent on the developmental
      course of their impulsiveness. METHOD: Data came from a sample of boys (N = 503)
      who were followed annually from approximate age 8 to age 18 and again at
      approximate age 24/25. Heavy drinking was defined as experiencing a blood alcohol
      concentration (BAC) level of 0.08% or higher. At each assessment, the parent and
      child each reported whether the child was impulsive. RESULTS: First, group-based
      trajectory analysis was used to identify 4 groups differing in the level and
      slopes of their trajectories of impulsive behavior from age 9 to age 17: low
      (13.9%), early adolescence-limited (18.7%), moderate (60.8%), and high (6.6%).
      These trajectory groups differed in their prevalence of any heavy drinking, peak
      BACs, and rates of alcohol dependence in adolescence and AUD in early adulthood,
      with the less impulsive groups being lower on these measures than the more
      impulsive groups. Heavy drinking was then entered into the model as a time
      varying covariate; this measure was lagged so that the results represent change
      in impulsive behavior the year following heavy drinking. Among boys on the
      moderate trajectory, those who drank heavily were rated as significantly more
      impulsive the following year compared to those who did not drink heavily.
      CONCLUSIONS: The association between heavy drinking and impulsive behavior may
      depend on earlier levels of impulsive behavior with those who are moderately
      impulsive appearing to be at greatest risk for increased impulsive behavior
      following heavy drinking. Further research is needed to clarify this association.

PMID- 21073487
TI  - The ability of Pseudomonas sp. LBUM 223 to produce phenazine-1-carboxylic acid
      affects the growth of Streptomyces scabies, the expression of thaxtomin
      biosynthesis genes and the biological control potential against common scab of
      potato.
AB  - Streptomyces scabies causes common scab, an economical disease affecting potato
      crops world-wide, for which no effective control measure exists. This pathogen
      produces the plant toxin thaxtomin A, which is involved in symptom development on
      potato tubers. A biological control approach that can limit S. scabies growth and
      repress thaxtomin production represents an attractive alternative to classical
      control strategies. Pseudomonas sp. LBUM 223 produces phenazine-1-carboxylic acid
      (PCA), an antibiotic that inhibits the growth of plant pathogens and contributes
      to the biological control of plant diseases. In this study, the involvement of
      LBUM 223's PCA-producing ability in the growth inhibition of S. scabies,
      repression of thaxtomin biosynthesis genes (txtA and txtC) and the biological
      control of common scab of potato was investigated using a mutant defective in PCA
      production (LBUM 223phzC(-) ). Streptomyces scabies growth was inhibited to a
      significantly lesser degree by LBUM 223phzC(-) than by the wild type. LBUM 223
      also significantly repressed txtA and txtC expression in S. scabies and protected
      potato against disease, whereas LBUM 223phzC(-) did not. These results suggest
      that PCA production is central to the ability of LBUM 223 to limit pathogen
      growth, repress the expression of key pathogenicity genes and control common scab
      of potato.

PMID- 21073488
TI  - Most heat-tolerant rhizobia show high induction of major chaperone genes upon
      stress.
AB  - The aims of this study were to evaluate the temperature stress tolerance of
      chickpea rhizobia and to investigate whether tolerance is related to the species
      or the site of origin of the isolates. Additionally, the molecular bases of
      temperature stress tolerance in rhizobia were investigated, by comparing the
      expression of chaperone genes dnaKJ and groESL in thermotolerant and
      thermosensitive isolates. Tolerance to cold, heat and heat shock was evaluated
      for 53 mesorhizobia obtained from several provinces of Portugal and assigned to
      different species. Associations between isolates' tolerance phenotype and several
      provinces of origin were found. Some species groups were found to differ
      significantly in their ability to tolerate temperature stress. Analysis of the
      dnaK and groESL expression by Northern hybridization, using isolates from three
      species groups, showed an increase in the transcripts levels with heat, but not
      with cold stress. Interestingly, a higher induction of chaperone genes was
      detected in heat-tolerant isolates when compared with that of sensitive isolates
      of the same species. To our knowledge, this is the first analysis of chaperone
      genes' expression comparing tolerant and sensitive strains. The present study
      suggests a relationship between higher transcriptional induction of major
      chaperone genes and higher tolerance to heat in rhizobia.

PMID- 21073489
TI  - Identification of beta-propeller phytase-encoding genes in culturable
      Paenibacillus and Bacillus spp. from the rhizosphere of pasture plants on
      volcanic soils.
AB  - Phytate is one of the most abundant sources of organic phosphorus (P) in soils,
      but must be mineralized by phytase-producing bacteria to release P for plant
      uptake. Microbial inoculants based on Bacillus spp. have been developed
      commercially, but few studies have evaluated the ecology of these bacteria in the
      rhizosphere or the types of enzymes that they produce. Here, we studied the
      diversity of aerobic endospore-forming bacteria (EFB) with the ability to
      mineralize phytate in the rhizosphere of pasture plants grown in volcanic soils
      of southern Chile. PCR methods were used to detect candidate phytase-encoding
      genes and to identify EFB bacteria that carry these genes. This study revealed
      that the phytate-degrading EFB populations of pasture plants included species of
      Paenibacillus and Bacillus, which carried genes encoding beta-propeller phytase
      (BPP). Assays of enzymatic activity confirmed the ability of these rhizosphere
      isolates to degrade phytate. The phytase-encoding genes described here may prove
      valuable as molecular markers to evaluate the role of EFB in organic P
      mobilization in the rhizosphere.

PMID- 21073490
TI  - Diversity of RuBisCO and ATP citrate lyase genes in soda lake sediments.
AB  - Sediments from six soda lakes of the Kulunda Steppe (Altai, Russia) and from
      hypersaline alkaline lakes of Wadi Natrun (Egypt) were analyzed for the presence
      of cbb and aclB genes encoding key enzymes Ci assimilation (RuBisCO in Calvin
      Benson and ATP citrate lyase in rTCA cycles, respectively). The cbbL gene
      (RuBisCO form I) was found in all samples and was most diverse, while the cbbM
      (RuBisCO form II) and aclB were detected only in few samples and with a much
      lower diversity. The cbbL libraries from hypersaline lakes were dominated by
      members of the extremely haloalkaliphilic sulfur-oxidizing
      Ectothiorhodospiraceae, i.e. the chemolithotrophic Thioalkalivibrio and the
      phototrophic Halorhodospira. In the less saline soda lakes from the Kulunda
      Steppe, the cbbL gene comprised up to ten phylotypes with a domination of members
      of a novel phototrophic Chromatiales lineage. The cbbM clone libraries consisted
      of two major unidentified lineages probably belonging to chemotrophic sulfur
      oxidizing Gammaproteobacteria. One of them, dominating in the haloalkaline lakes
      from Wadi Natrun, was related to a cbbM phylotype detected previously in a
      hypersaline lake with a neutral pH, and another, dominating in lakes from the
      Kulunda Steppe, was only distantly related to the Thiomicrospira cluster. The
      aclB sequences detected in two samples from the Kulunda Steppe formed a single,
      deep branch in the Epsilonproteobacteria, distantly related to Arcobacter
      sulfidicus.

PMID- 21073491
TI  - Does moonlight influence the biting behaviour of Anopheles funestus?
AB  - The possible effect of moonlight on the biting behaviour of mosquitoes in
      southern Mozambique, in particular that of Anopheles funestus (Diptera:
      Culicidae), a primary vector of malaria, was investigated by comparing catches
      indoors and outdoors using CDC light traps and 'Furvela' tent traps,
      respectively, for 35 consecutive nights, from 9 September to 15 October 2008.
      Collections were separated into three 4-hourly samples each night. A total of 17
      591 mosquitoes belonging to nine species were collected, 6747 in light traps and
      10 844 in tent traps. Anopheles funestus (n = 7634) and Mansonia africana (n =
      4859) were the most abundant species. Fluctuations in temperature and humidity
      were the two environmental variables associated with changes in relative
      abundance of mosquitoes. Most An. funestus were collected indoors, with the
      majority collected in the first 4 h of the night. This was most evident on nights
      when moonlight was present in the early part of the night. A total of 3488 An.
      funestus were dissected for gonotrophic age determination. Parous rates did not
      change with lunar phase, but estimated oviposition cycle length was significantly
      shorter on nights when moonlight was present at the time of oviposition.
      Moonlight at dusk did not, however, affect the proportion of newly emerged
      insects with mating plugs collected. Outdoor transmission of malaria, especially
      on moonlit nights, remains a problem for control programmes.

PMID- 21073492
TI  - First report of the repellency of 2-tridecanone against ticks.
AB  - 2-Tridecanone and 2-undecanone are both found naturally in the trichomes of wild
      tomato plants and are important in plant resistance to herbivory. 2-Undecanone is
      the U.S. Environmental Protection Agency (EPA)-registered active ingredient in
      the commercially available arthropod repellent, BioUD((r)) . The goal of this
      study was to examine the tick repellency of 2-tridecanone. Two-choice bioassays
      were conducted using 8% 2-tridecanone vs. the repellent carrier (absolute
      ethanol) and compared with two-choice studies using 8% 2-undecanone vs. absolute
      ethanol. Unfed, host-seeking adult (mixed sex) Amblyomma americanum (L.) (Acari:
      Ixodidae) and Dermacentor variabilis Say (Acari: Ixodidae) were used to evaluate
      repellency and time to repellent failure at room temperature. The present study
      shows in filter paper assays (0.63 mg test compound/cm(2) ) that 2-tridecanone
      was 87% repellent to A. americanum at 12 h after application, but had no
      statistically significant repellency at 15 h and 24 h, and was 72% repellent to
      D. variabilis at 15 h, but had no statistically significant repellency at 24 h.
      By contrast, 2-undecanone was 74% and 75% repellent to A. americanum and D.
      variabilis, respectively, at 2 h after application, but no statistically
      significant repellency was noted at 2.5 h and 3 h. In two-choice assays on
      cheesecloth, 2-tridecanone at 0.25 mg/cm(2) was 85% repellent to A. americanum 6
      h after application, demonstrating its potential use as an arthropod repellent
      that can be used on clothing without the need for formulation. No statistically
      significant repellency was found at 9 h or 12 h. The potential use of 2
      tridecanone as a tick repellent is discussed.

PMID- 21073493
TI  - Evaluation of juvenile hormone analogues as rodent feed-through insecticides for
      control of immature phlebotomine sandflies.
AB  - The juvenile hormone analogues methoprene and pyriproxyfen were evaluated as
      rodent feed-through insecticides for control of immature stages of the sandfly
      Phlebotomus papatasi Scopoli (Diptera: Psychodidae). The development and survival
      of P. papatasi second-instar larvae fed faeces from Syrian hamsters, Mesocricetus
      auratus, that had been fed a diet containing methoprene (0, 9.788, 97.88 or 978.8
      p.p.m.) or pyriproxyfen (0, 9.82, 98.2 or 982 p.p.m.) were evaluated. The faeces
      of methoprene-treated hamsters greatly reduced the percentage of larvae that
      pupated at all concentrations tested and prevented adult emergence at all but the
      lowest concentration (9.788 p.p.m.). Pyriproxyfen prevented both pupation and
      adult emergence at all concentrations tested. The results of this study suggest
      that a control strategy using rodent baits containing juvenile hormone analogues
      to control phlebotomine sandflies that live in rodent burrows and feed on rodent
      faeces may be possible. As rodent reservoirs and vectors of Leishmania major live
      in close association in many parts of the Middle East, control of the
      transmission of the agent of zoonotic cutaneous leishmaniasis may also be
      possible.

PMID- 21073494
TI  - Detection of the highly leucotoxic JP2 clone of Aggregatibacter
      actinomycetemcomitans in members of a Caucasian family living in Sweden.
AB  - BACKGROUND: carriers of the JP2 clone of Aggregatibacter actinomycetemcomitans
      exhibit an enhanced risk for developing aggressive periodontitis compared with
      individuals carrying non-JP2 clones. While the JP2 clone is almost exclusively
      detected among adolescents of African descent, reports on Caucasians colonized
      with the JP2 clone are remarkably few. OBJECTIVE: the aim of this paper is to
      report on the history of periodontal disease and microbiological findings in a
      Caucasian family. MATERIAL AND METHODS: a. actinomycetemcomitans and other
      periodontitis-associated bacterial species in subgingival plaque samples were
      quantified by conventional culture technique. Leucotoxin promoter typing,
      serotyping and further characterizations of A. actinomycetemcomitans isolates
      were performed by PCR. DNA sequencing of the pseudogene, hbpA was performed to
      determine the origin of the detected JP2 clones. Further, genetically ancestry
      testing of family members was carried out. RESULTS: the JP2 clone was detected in
      samples from two of the family members, a 33-year-old daughter and her 62-year
      old mother. Relationship of their JP2 clones with JP2 clone strains from the
      Mediterranean area of Africa was indicated. Genotyping confirmed the Caucasian
      origin of all family members. CONCLUSIONS: Caucasian JP2 carriers exist and older
      subjects can carry the JP2 clone of A. actinomycetemcomitans.

PMID- 21073495
TI  - The dental patient on oral anticoagulant medication: a literature review.
AB  - Specific diseases and medications may considerably influence the delivery of oral
      care and the course of dental therapy. The purpose of this literature review is
      to examine the relationship between oral anticoagulant medication and dental
      treatment. Electronic and manual searches were conducted for clinical studies in
      the English literature for the years 1988-2010. The review process provided a
      total of 110 pertinent literature references, out of which 38 studies dealt with
      oral anticoagulants and dental treatment. Different treatment strategies relative
      to dental periprocedural anticoagulation regimens have been identified, and their
      accompanying thromboembolic and bleeding risks are being presented and discussed.
      Regarding to what extent a safe and successful dental treatment in patients on
      anticoagulant medication is feasible, the level of evidence is lacking. Until
      high-level data are provided, an individualised treatment approach after
      consultation with the physician of the patient is highly recommended.

PMID- 21073496
TI  - TP53, beta-Catenin and c-myc/N-myc status in embryonal tumours with
      ependymoblastic rosettes.
AB  - BACKGROUND: The primitive neuroectodermal tumours of central nervous system (CNS
      PNET) are a heterogeneous group of neoplasms, occurring in the CNS and composed
      of undifferentiated or poorly differentiated neuroepithelial cells which may
      display divergent differentiation along neuronal, astrocytic and ependymal lines.
      The WHO classification includes in this group of tumours also ependymoblastomas
      and medulloepitheliomas. Several groups have reported examples of CNS-PNET with
      combined histological features of ependymoblastoma and neuroblastoma, defined as
      'embryonal tumour with abundant neuropil and true rosettes'. The presence of the
      amplification of chromosome region 19q13.42, common in both ependymoblastoma and
      embryonal tumour with abundant neuropil and true rosettes, suggests that they
      represent a histological spectrum of a single biological entity. METHODS: We
      examined 24 cases of ependymoblastoma/embryonal tumour with abundant neuropil and
      true rosettes (EPBL/ETANTR) for the presence of mutations of TP53 and beta
      Catenin and for amplification of c-myc/N-myc. RESULTS: The single strand
      conformation polymorphism-mutational screening did not identify any mutation in
      exons 5 to 8 of the TP53 gene. However, we found a point mutation affecting codon
      34 (GGA -> GTA) of beta-Catenin gene resulting in a Glycine -> Valine
      substitution. No cases presented c-myc/N-myc amplification. CONCLUSIONS:
      EPBL/ETANTRs show molecular features different from other CNS-PNET and
      medulloblastomas. The presence of alterations in the beta-Catenin/WNT pathway
      seems to be noteworthy due to the close relationship between this pathway and miR
      520g encoded in chromosome 19q13.42 region amplified in these tumours.

PMID- 21073497
TI  - Advancing evidence-based nursing practice through explicit theory-testing
      research: focus on the sixth vital sign, fatigue.

PMID- 21073499
TI  - Vulnerability in homeless adolescents: concept analysis.
AB  - AIM: This paper is a report of an analysis of the concept of vulnerability in
      homeless adolescents. BACKGROUND: Caring for vulnerable populations and reduction
      of health inequities are top international healthcare priorities. Homeless
      adolescents experience health disparities as compared to their housed
      counterparts and are among the most vulnerable of all populations. Understanding
      the concept of vulnerability as it relates to the homeless adolescent population
      will assist nurses in addressing the health and social concerns of this
      population. DATA SOURCES: The PubMed, Medline, Cochrane and CINAHL electronic
      databases were used to search for research papers published between 1980 and
      2009. The keywords 'vulnerable', 'vulnerability' and 'homeless', 'adolescent',
      'street' and 'youth' were used. Twenty-three papers from multiple disciplines
      were reviewed in an effort to arrive at a global definition of homeless
      adolescents' vulnerability. METHOD: Rodgers' evolutionary method of concept
      analysis was used for the analysis. RESULTS: Based on this analysis,
      vulnerability in homeless adolescents is defined as the constellation of past,
      present and future risk, perceived or real, because of the common human
      experience of risk, the increased vulnerability of the adolescent period, the
      consequences of family disruption, and the increased risks of life on the street.
      CONCLUSION: There was agreement in the literature regarding the antecedents,
      attributes, consequences and surrogate terms of the concept. However,
      differentiation between the concepts of risk and vulnerability, as suggested by
      seminal nurse researchers, was not supported. More research is needed into self
      perceptions of vulnerability and vulnerability in subgroups of homeless
      adolescents.

PMID- 21073500
TI  - In response to: Simmons (2010) Clinical reasoning: concept analysis. Journal of
      Advanced Nursing 66 (5), 1151-1158.

PMID- 21073502
TI  - Nurse prescribing roles in acute care: an evaluative case study.
AB  - AIM: This paper is a report of an evaluation of the implementation of nurse
      prescribing in an acute care hospital in England. BACKGROUND: At the time of the
      study, evaluation of nurse prescribing had taken place in community settings, but
      little was known about its impact and effectiveness in acute care. Although nurse
      prescribing has permitted doctor-nurse substitution in acute episodic care, some
      doctors have expressed concerns about patient safety in relation to nurse
      prescribing. METHODS: A mixed methods single-case study was conducted in 2005-06,
      using purposive sampling. Semi-structured interviews were carried out with 18
      hospital staff, non-participant observation of two nurses and two doctors
      undertaking 52 patient-prescriber consultations with 47 patients, and a
      questionnaire survey with 122 patients (response rate 61%: n=74). RESULTS: Nurse
      prescribing was found to benefit patients through service delivery improvement
      and using staff skills differently. Nurse prescribers and their colleagues were
      positive about role and service changes and their impact on patient care. No
      differences were found between the ways in which nurses and doctors performed
      prescribing roles, but there was a statistically significant difference between
      the medication-related information satisfaction ratings of patients who had seen
      a nurse prescriber, compared to those seen by a doctor. CONCLUSION: Nurses and
      doctors were found to provide equivalent care. Shared vision, local champions,
      action learning and peer support were the enabling factors that helped to embed
      the new prescribing roles within the study site.

PMID- 21073503
TI  - Risk factors associated with transfer anxiety among patients transferring from
      the intensive care unit to the ward.
AB  - AIM: This paper is a report of an examination of the effect of risk factors on
      the development of transfer anxiety in patients being transferred from the
      intensive care unit to the ward. BACKGROUND: Transfer of a patient from the
      intensive care unit to the ward could lead to transfer anxiety, a type of
      separation anxiety associated with transfer from a secure and familiar
      environment to an unfamiliar one. Previous studies have demonstrated associations
      between hospital anxiety and demographic, clinical and social factors. METHOD:
      Data were collected from 100 patients who were transferred from intensive care
      unit to the ward, using medical records and three self-report questionnaires
      (Hospital Anxiety and Depression Scale, Medical Outcomes Study-Social Support
      Scale, Health Care System Distrust Scale), completed within 72 hours of transfer,
      between 2005 and 2006. Spearman Rho correlations were used to determine
      relationships between variables. FINDINGS: A statistically significant
      relationship was found between amount of social support (r(s)=-0.21, P=0.04),
      length of intensive care unit hospitalization (r(s)=0.21, P=0.04) and gender
      (U=907.0, P=0.03) with transfer anxiety. No statistically significant
      relationships were found between transfer anxiety and other factors. CONCLUSION:
      Nurses should be especially aware of an increased risk for transfer anxiety among
      women, and those with lower social support and longer intensive care unit length
      of stay. We recommend that interventions, especially targeted to these
      populations, be developed to decrease its prevalence.

PMID- 21073504
TI  - The relationship between substance use and exit security on psychiatric wards.
AB  - AIM: In this paper we report on the rates of drug/alcohol use on acute
      psychiatric wards in relation to levels and intensity of exit security measures.
      BACKGROUND: Many inpatient wards have become permanently locked, with staff
      concerned about the risk of patients leaving the ward and harming themselves or
      others, and of people bringing illicit substances into the therapeutic
      environment. METHODS: In 2004/2005, a cross sectional survey on 136 acute
      psychiatric wards across three areas of England was undertaken. A comprehensive
      range of data including door locking and drug/alcohol use were collected over 6
      months on each ward. In 2006, supplementary data on door locking and exit
      security were collected. Door locking, additional exit security measures and
      substance misuse rates of the 136 wards were analysed and the associations
      between these were investigated. RESULTS: No consistent relationships were found
      with exit security features, intensity of drug/alcohol monitoring procedures, or
      the locking of the ward door. There were indications that use of breath testing
      for alcohol might reduce usage and that the use of 'sniffer' dogs was associated
      with greater alcohol use. CONCLUSION: Greater exit security or locking of the
      ward door had no influence on rates of use of alcohol or illicit drugs by
      inpatients and thus cannot form part of any strategy to control substance use by
      inpatients. There are some grounds to believe that a greater use of screening
      might help reduce the frequency of alcohol/substance use on wards and may lead to
      a reduction in verbal abuse.

PMID- 21073505
TI  - Involving older people in research: practical considerations when using the
      authenticity criteria in constructivist inquiry.
AB  - AIM: The purpose of this paper is to identify practical suggestions that could
      enable other researchers to consider how quality may be evidenced using
      constructivist principles including the perspectives of older people and their
      caregivers. BACKGROUND: Constructivism suggests that reality is part of a social
      construction, which holds different meanings for each person, in which people are
      active agents, making autonomous decisions. This approach to research has been
      identified as suitable for health and social care professionals because these
      underpinning principles reflect the values of these professions, facilitating the
      involvement of users and carers. The authenticity criteria have been developed to
      reflect these philosophical principles but have been criticized for their
      inaccessible language. To incorporate user and carer perspectives, the criteria
      have been revised into a more accessible model matrix known as the AldreVast
      Sjuharad criteria. DISCUSSION: This paper reports on two constructivist studies
      that explored relationships between older people, families and staff in different
      settings--the community and care homes. Examples from both settings demonstrate
      how the perspectives of users and carers were incorporated throughout the
      research process. Following the AldreVast Sjuharad model matrix, practical
      guidance is provided on how the quality of constructivist research may be
      implemented in nursing research. CONCLUSIONS: The different settings in this
      paper influenced how the AldreVast Sjuharad model matrix was applied. Further
      work is needed in exploring how the perspective of users and carers may be
      incorporated into the quality process of constructivist research.

PMID- 21073507
TI  - The role of the organisational psychologist in disasters and emergency
      situations.
AB  - Interventions in extreme situations, such as natural or technological disasters,
      terrorist attacks or emergencies in general, take place in settings of great
      uncertainty and are always accompanied by extraordinary circumstances. For this
      reason, there are various processes related to implementing intervention
      protocols that must be carefully examined, including an evaluation of work
      scenarios, personnel selection, within-group relationships in work teams,
      decision-making processes, or certain peculiarities of burnout among emergency
      personnel. In the view of this author, an ad hoc review of the role of the
      organisational psychologist can highlight interesting analysis and performance
      possibilities that could make work in emergency and disasters contexts more
      effective. The aim of this paper is to provide an overview of the role of the
      organisational psychologist pre-and post-disaster. Furthermore, it supports the
      idea that professional profiles must be designed that take into account specific
      knowledge and skills, as well as certain aptitudes and values.

PMID- 21073506
TI  - Scales for assessing self-efficacy of nurses and assistants for preventing falls.
AB  - AIM: This paper is a report of the development and testing of the Self-Efficacy
      for Preventing Falls Nurse and Assistant scales. BACKGROUND: Patient falls and
      fall-related injuries are traumatic ordeals for patients, family members and
      providers, and carry a toll for hospitals. Self-efficacy is an important factor
      in determining actions persons take and levels of performance they achieve.
      Performance of individual caregivers is linked to the overall performance of
      hospitals. Scales to assess nurses and certified nursing assistants' self
      efficacy to prevent patients from falling would allow for targeting resources to
      increase SE, resulting in improved individual performance and ultimately
      decreased numbers of patient falls. METHOD: Four phases of instrument development
      were carried out to (1) generate individual items from eight focus groups (four
      each nurse and assistant conducted in October 2007), (2) develop prototype
      scales, (3) determine content validity during a second series of four nurse and
      assistant focus groups (January 2008) and (4) conduct item analysis, paired t
      tests, Student's t-tests and internal consistency reliability to refine and
      confirm the scales. Data were collected during February-December, 2008. RESULTS:
      The 11-item Self-Efficacy for Preventing Falls Nurse had an alpha of 0.89 with
      all items in the range criterion of 0.3-0.7 for item total correlation. The 8
      item Self-Efficacy for Preventing Falls Assistant had an alpha of 0.74 and all
      items had item total correlations in the 0.3-0.7 range. CONCLUSIONS: The Self
      Efficacy for Preventing Falls Nurse and Self-Efficacy for Preventing Falls
      Assistant scales demonstrated psychometric adequacy and are recommended to
      measure bedside staff's self-efficacy beliefs in preventing patient falls.

PMID- 21073508
TI  - Extreme weather events and related disasters in the Philippines, 2004-08: a sign
      of what climate change will mean?
AB  - Being an archipelagic nation, the Philippines is susceptible and vulnerable to
      the ill-effects of weather-related hazards. Extreme weather events, which include
      tropical cyclones, monsoon rains and dry spells, have triggered hazards (such as
      floods and landslides) that have turned into disasters. Financial resources that
      were meant for development and social services have had to be diverted in
      response, addressing the destruction caused by calamities that beset different
      regions of the country. Changing climatic patterns and weather-related
      occurrences over the past five years (2004-08) may serve as an indicator of what
      climate change will mean for the country. Early recognition of this possibility
      and the implementation of appropriate action and measures, through disaster risk
      management, are important if loss of life and property is to be minimised, if not
      totally eradicated. This is a matter of urgent concern given the geographical
      location and geological characteristics of the Philippines.

PMID- 21073509
TI  - Escaping to and being active in neighbourhood parks: park use in a post-disaster
      setting.
AB  - Neighbourhood parks may serve as a coping resource in post-disaster communities,
      yet little is known about the impact of large-scale disasters on park use. The
      objective of this study is to explore the impact of Hurricane Katrina (August
      2005) on park use by visitors from flooded areas of New Orleans, Louisiana,
      compared to visitors from non-flooded areas. In 2006 and 2007, following
      Hurricane Katrina, 201 adults who visited 27 New Orleans parks were interviewed.
      Visitors from flooded neighbourhoods used their parks less often and were less
      likely to engage in animal interaction than visitors from non-flooded
      neighbourhoods. They placed more importance on escape and physically-active
      motivations than visitors from non-flooded areas. Social reasons were also more
      important to visitors from flooded areas, but these differences disappeared after
      adjusting for race. Neighbourhood parks are a community asset that may play a
      role in the post-disaster recovery process by providing opportunities for escape
      and physical activity.

PMID- 21073510
TI  - ISPsa2, the first mobile genetic element to be described and characterized in the
      bacterial facultative intracellular pathogen Piscirickettsia salmonis.
AB  - Piscirickettsia salmonis is a novel, aggressive, facultative Gram-negative
      bacterium that drastically affects salmon production at different latitudes, with
      particular impact in southern Chile. Initially, P. salmonis was described as a
      Rickettsia-like, obligate, intracellular Alphaproteobacteria, but it was
      reclassified recently as a facultative intracellular Gammaproteobacteria. This
      designation has prompted the independent growth of the bacterium to a pure state
      for detailed study of its biology, genetics and epidemiology, properties that are
      still relatively poorly characterized. The preliminary sequence analysis of a 992
      bp fragment of pure P. salmonis DNA allowed us to characterize a novel and
      complete 863-bp insertion sequence in the bacterial genome (named ISPsa2), which
      has a novel 16/16bp perfectly inverted terminal repeat flanking a 726-bp ORF that
      encodes a putative transposase (Tnp-Psa). The coding sequence of the enzyme
      shares similarities to that described in some Bacillus species and particularly
      to those of the IS6 family. ISPsa2 carries its own promoter with standard -10 and
      -35 sequences, suggesting an interesting potential for plasticity in this
      pathogenic bacterium. Additionally, the presence of ISPsa2 was confirmed from
      three isolates of P. salmonis collected from different epizootics in Chile in
      2010.

PMID- 21073511
TI  - Persistence and spread of Salmonella enterica serovar Weltevreden in soil and on
      spinach plants.
AB  - Several outbreaks caused by pathogenic bacteria are related to the consumption of
      raw produce contaminated by animal manure. The majority of these outbreaks have
      been linked to Salmonella spp. We examined the ability of Salmonella enterica
      serovar Weltevreden to persist and survive in manure and soil as well as
      disseminate to, and persist on, spinach roots and leaves. Significantly higher
      numbers of S. Weltevreden inoculated into manure and applied to soil before
      planting spinach were found in soil than in pot cultures, where the pathogen had
      been inoculated directly into soil 14 days postplanting. Moreover, the pathogen
      seemed to disperse from manure to spinach roots, as we observed a continuous
      increase in the number of contaminated replicate pot cultures throughout the
      evaluation period. We also found that, in some cases, S. Weltevreden present in
      the phyllosphere had the ability to persist for the entire evaluation period (21
      days), with only slight reductions in cell numbers. The results from the present
      study show that S. Weltevreden is capable of persisting in soil, roots and shoots
      for prolonged periods, indicating the importance of strict monitoring of
      untreated animal manure before considering its application to agricultural land.

PMID- 21073512
TI  - Dermatofibrosarcoma protuberans arising in the context of Shwachman-Diamond
      syndrome.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant spindle-cell
      tumor usually presenting in adulthood. The epidemiology of DFSP has recently been
      reviewed, and there have been 152 reported cases of DFSP in patients below the
      age of sixteen. We present the case of a DFSP arising in a young patient with
      Shwachman-Diamond syndrome (SDS).

PMID- 21073513
TI  - Usefulness and Limitation of Transthoracic Echocardiography in the Diagnosis of
      Large Coronary Artery Fistula.

PMID- 21073514
TI  - Decrease in left atrium volume after successful balloon mitral valvuloplasty: an
      echocardiographic and hemodynamic study.
AB  - BACKGROUND: Left atrium (LA) remodeling has a crucial adverse impact on outcome
      and prognosis in mitral stenosis. Few studies have reported the effect of balloon
      mitral valvuloplasty (BMV) on LA volume. The aim of this study was to assess the
      evolution of LA volume immediately and 1 month after successful BMV in patients
      in sinus rhythm. METHODS: Thirty-three consecutive patients (70% women; age 31 +/
      8 years; range 19-45) with moderate to severe mitral stenosis (mitral valve area
      <=1.5 cm(2) ) who underwent successful BMV were included prospectively. Using two
      dimensional echocardiography, and according to the prolate ellipse method, LA
      volume and LA volume indexed to body surface area were determined before BMV, and
      24 hours and 1 month after BMV. Tricuspid and pulmonary regurgitation jets were
      recorded systematically using continuous-wave Doppler. Pulmonary artery-right
      ventricular (PA-RV) gradients, reflecting pulmonary pressures, and pulmonary
      vascular resistance were measured. RESULTS: Mitral valve area increased from 0.88
      +/- 0.16 to 1.55 +/- 0.26 cm(2) (P < 0.0001). Mean mitral valve gradient (MVG)
      decreased from 16 +/- 6 to 6 +/- 2 mmHg (P < 0.0001) immediately after BMV.
      Indexed LA volume fell from 56 +/- 14 to 48 +/- 12 mL/m(2) (P = 0.0002)
      immediately after BMV and to 45 +/- 13 mL/m(2) at 1 month (P < 0.0001). Only
      patients with a median LA volume >=55 mL/m(2) before BMV had a significant
      reduction in LA volume (P = 0.0001). Decrease in LA volume was correlated with
      decreases in PA-RV peak diastolic gradient (r = 0.45, P = 0.008) and MVG (r =
      0.35, P = 0.04). CONCLUSION: In patients with mitral stenosis in sinus rhythm,
      successful BMV results in an immediate decrease in LA volume. This reduction,
      maximal immediately after BMV, correlates with decreases in MVG and PA-RV peak
      diastolic gradient, and is significant only when LA volume before BMV is severely
      enlarged.

PMID- 21073515
TI  - Accuracy of handheld echocardiography for bedside diagnostic evaluation in a
      tertiary cardiology center: comparison with standard echocardiography.
AB  - AIMS: We aimed to assess the clinical role of a basic handheld echocardiographic
      device (HHE) used during cardiology training in evaluating different functional
      and morphological elements of the heart. METHODS AND RESULTS: 56 consecutive
      patients (pts), 26 women, mean age 60.0 +/- 11.9 years admitted in our Cardiology
      Department had an echocardiogram performed by both cardiology trainees using a
      HHE with B-mode capabilities only and by cardiologists with advanced training in
      echocardiography using a standard echocardiography device (SE). Several
      parameters were analyzed: the presence of wall motion abnormalities (WMA), aortic
      valve abnormalities (AVAbn), mitral valve abnormalities (MVAbn), the presence of
      pericardial effusion (PE), as well as the presence of a dilated (LVD) or
      hypertrophied left ventricle (LVH). The Kappa coefficient of correlation between
      the two methods (k) was determined, along with the sensitivity (Sn), specificity
      (Sp), negative predictive value (NPV), and positive predictive value (PPV). Both
      HHE and SED examinations were possible in 52 of the 56 pts (92.8% feasibility).
      There was a moderate correlation in the assessment of WMA (k = 0.56) with a
      substantial agreement for MVAbn (k = 0.72), AVAbn (k = 0.76), LVH (k = 0.67)
      There was excellent agreement for LVD (k = 0.81). Valvular diseases were
      determined by HHE with good Sp (MVAbn - 97.4%, AVAbn - 100%), although the Sn and
      NPV were lower. CONCLUSIONS: Bedside evaluation using HHE is helpful for
      assessing LV chamber and walls dimensions, LV regional function, and
      morphological abnormalities of the valves. The device can be used by cardiology
      trainees with limited experience in echocardiography but only in combination with
      a standard examination.

PMID- 21073516
TI  - Transient pseudorestrictive pattern of transmitral flow velocity curve in
      patients with paroxysmal atrial fibrillation.
AB  - BACKGROUND: Early diastolic velocity of the mitral annulus and transmitral flow
      propagation velocity are reported as more reliable determinants of left
      ventricular diastolic function in patients with atrial fibrillation than are
      transmitral Doppler indices. This study aimed to test the hypothesis that
      transmitral flow curve shows pseudorestrictive pattern during rate-controlled
      atrial fibrillation. METHODS: Thirteen paroxysmal atrial fibrillation patients
      were monitored for three phases: before atrial fibrillation, during atrial
      fibrillation, and after the recovery of atrial fibrillation to sinus rhythm.
      Standard two-dimensional, color flow, and tissue Doppler echocardiography were
      performed. We compared the indices of left ventricular diastolic function among
      the three phases. RESULTS: The early diastolic velocity of transmitral flow
      increased significantly during atrial fibrillation (before, 0.76 +/- 0.19 m/sec;
      during, 0.86 +/- 0.20 m/sec; after recovery to sinus rhythm, 0.73 +/- 0.16 m/sec;
      P < 0.01). The deceleration time of early transmitral diastolic wave decreased
      during atrial fibrillation (182.5 +/- 39.6 ms; 149.1 +/- 38.7 ms; 184.0 +/- 44.5
      ms, respectively, P < 0.01). The early diastolic velocity of the mitral annulus
      increased during atrial fibrillation (5.37 +/- 1.31 cm/sec; 7.29 +/- 1.25 cm/sec;
      5.37 +/- 1.32 cm/sec; respectively, P < 0.01). The transmitral propagation
      velocity did not change significantly during atrial fibrillation. CONCLUSION:
      Although conventional Doppler indices showed abnormal relaxation pattern, left
      ventricular diastolic function was preserved during rate-controlled atrial
      fibrillation, as determined from early diastolic velocity of the mitral annulus
      and transmitral flow propagation velocity.

PMID- 21073517
TI  - The role of melatonin in glaucoma: implications concerning pathophysiological
      relevance and therapeutic potential.
AB  - Glaucoma is a frequent ophthalmologic condition leading to chronic progressive
      optic neuropathy, which can result in visual impairment and blindness. In
      addition, glaucoma is associated with a dysregulation of circadian rhythms, as
      well as with a high incidence of sleep disorders, depression, and anxiety.
      However, because of their high comorbidity in older age, these conditions have
      not received much scientific attention and are often undertreated. In the current
      paper, we review the available literature on the role of melatonergic mechanisms
      in glaucoma, regulation of circadian rhythms, and depression. The literature is
      presented as a narrative review, providing an overview on the most important and
      clinically relevant publications. Recently, there has been evidence for a
      progressive loss of intrinsically photosensitive retinal ganglion cells (ipRGC)
      because of oxidative stress in glaucoma. As ipRGC are responsible for the photic
      transduction to the circadian system and subsequent melatonin secretion, and
      melatonin is involved in the pathophysiology of circadian desynchronization,
      sleep disorder, and depression, an impairment of photo-dependent melatonergic
      signaling may be a common pathway connecting glaucoma with these comorbidities.
      This fact, as well as the proven retinal neuroprotective role of melatonin,
      suggests that melatonergic drugs provide a potentially promising treatment
      strategy supplementing the management of intraocular pressure by pharmacological
      and surgical measures. Additionally, multidisciplinary treatment focusing on
      depression and normalization of circadian rhythms might be beneficial for
      glaucoma patients. Furthermore, glaucoma might be a useful model for studying the
      pathophysiological interactions between the melatonergic, circadian, and mood
      systems.

PMID- 21073518
TI  - Melatonin improves the survival of cryopreserved callus of Rhodiola crenulata.
AB  - An important aspect of the function of melatonin seems to be the mediation of
      stress caused by environmental and chemical factors. In the cryopreservation
      process, environmental changes including osmotic injury, desiccation, and low
      temperature can impose a series of stresses on plants. In this study, we
      evaluated the role of melatonin in stress protection during the process of
      cryopreservation using callus of an endangered plant species Rhodiola crenulata.
      The survival rate of the cryopreserved callus significantly increased when the
      callus was pretreated for 5 days with 0.1 MUm melatonin prior to freezing in
      liquid nitrogen. Analysis of antioxidative activity following the pretreatment of
      callus with 0.1 MUm melatonin showed a significant reduction in malondialdehyde
      production during various steps of cryopreservation. Enhanced peroxidase and
      catalase activity was observed in the callus after pretreatment with 0.1 MUm
      melatonin compared to the control. These observations provide new evidence of the
      antioxidant/anti-stress function of melatonin, and it is the first report of its
      potential application in the preservation of elite endangered germplasm through
      the process of cryopreservation.

PMID- 21073519
TI  - Melatonin synergistically increases resveratrol-induced heme oxygenase-1
      expression through the inhibition of ubiquitin-dependent proteasome pathway: a
      possible role in neuroprotection.
AB  - Melatonin is an indoleamine secreted by the pineal gland as well as a plant
      derived product, and resveratrol (RSV) is a naturally occurring polyphenol
      synthesized by a variety of plant species; both molecules act as a neuroprotector
      and antioxidant. Recent studies have demonstrated that RSV reduced the incidence
      of Alzheimer's disease and stroke, while melatonin supplementation was found to
      reduce the progression of the cognitive impairment in AD. The heme oxygenase-1
      (HO-1) is an inducible and redox-regulated enzyme that provides tissue-specific
      antioxidant effects. We assessed whether the co-administration of melatonin and
      RSV shows synergistic effects in terms of their neuroprotective properties
      through HO-1. RSV significantly increased the expression levels of HO-1 protein
      in a concentration-dependent manner both in primary cortical neurons and in
      astrocytes, while melatonin per se did not. Melatonin + RSV showed a synergistic
      increase in the expression levels of HO-1 protein but not in the HO-1 mRNA level
      compared to either melatonin or RSV alone, which is mediated by the activation of
      PI3K-Akt pathway. Treatment of melatonin + RSV significantly attenuated the
      neurotoxicity induced by H(2) O(2) in primary cortical neurons and also in
      organotypic hippocampal slice culture. The blockade of HO-1 induction by shRNA
      attenuated HO-1 induction by melatonin + RSV and hindered the neuroprotective
      effects against oxidative stress induced by H(2) O(2) . The treatment of MG132 +
      RSV mimicked the effects of melatonin + RSV, and melatonin + RSV inhibited
      ubiquitination of HO-1. These data suggest that melatonin potentiates the
      neuroprotective effect of RSV against oxidative injury, by enhancing HO-1
      induction through inhibiting ubiquitination-dependent proteasome pathway, which
      may provide an effective means to treat neurodegenerative disorders.

PMID- 21073520
TI  - Chronic melatonin consumption prevents obesity-related metabolic abnormalities
      and protects the heart against myocardial ischemia and reperfusion injury in a
      prediabetic model of diet-induced obesity.
AB  - Obesity, a major risk factor for ischemic heart disease, is associated with
      increased oxidative stress and reduced antioxidant status. Melatonin, a potent
      free radical scavenger and antioxidant, has powerful cardioprotective effects in
      lean animals but its efficacy in obesity is unknown. We investigated the effects
      of chronic melatonin administration on the development of the metabolic syndrome
      as well as ischemia-reperfusion injury in a rat model of diet-induced obesity
      (DIO). Male Wistar rats received a control diet, a control diet with melatonin, a
      high-calorie diet, or a high-calorie diet with melatonin (DM). Melatonin (4
      mg/kg/day) was administered in the drinking water. After 16 wk, biometric and
      blood metabolic parameters were measured. Hearts were perfused ex vivo for the
      evaluation of myocardial function, infarct size (IFS) and biochemical changes
      [activation of PKB/Akt, ERK, p38 MAPK, AMPK, and glucose transporter (GLUT)-4
      expression). The high-calorie diet caused increases in body weight (BW), visceral
      adiposity, serum insulin and triglycerides (TRIG), with no change in glucose
      levels. Melatonin treatment reduced the BW gain, visceral adiposity, blood TRIG,
      serum insulin, homeostatic model assessment index and thiobarbituric acid
      reactive substances in the DIO group. Melatonin reduced IFS in DIO and control
      groups and increased percentage recovery of functional performance of DIO hearts.
      During reperfusion, hearts from melatonin-treated rats had increased activation
      of PKB/Akt, ERK42/44 and reduced p38 MAPK activation. Chronic melatonin treatment
      prevented the metabolic abnormalities induced by DIO and protected the heart
      against ischemia-reperfusion injury. These beneficial effects were associated
      with activation of the reperfusion injury salvage kinases pathway.

PMID- 21073521
TI  - Variability in paediatric outcomes within wealthy countries.
AB  - Our Different View was stimulated by our analyses that identified very different
      risks of preterm birth (and most likely their outcomes) in the Aboriginal
      subpopulation of Western Australia. Given the increasing immigration into many
      wealthy countries in both North America and Europe, it is unlikely that these
      patterns we described are unique to Australia. Hence, our thoughts about the
      causes of disparities and ways to minimize them may well help others have a
      different view and approach to this universal paediatric issue.

PMID- 21073522
TI  - Intravenous leiomyomatosis with intracardiac extension: a report of two cases.
AB  - Uterine leiomyoma is a common disease in women; however, intravenous
      leiomyomatosis with intracaval and intracardiac complications is a rare
      condition. The initial presentation is dependent upon the severity of the
      intracardiac involvement. In this report, we describe two women with
      leiomyomatosis originating from the uterus and extending into the inferior vena
      cava to the right ventricle that was successfully resected using a two-stage
      approach. 

PMID- 21073523
TI  - Persistent left ventricular false aneurysm after transapical insertion of an
      aortic valve.
AB  - Transcatheter aortic valve implantation (TAVI), via either a femoral or apical
      approach, has been developed as an alternative to conventional aortic valve
      replacement for patients whose operative risks are considered too high for
      conventional surgery. Complications with these relatively new procedures are
      being reported with increasing frequency. We report a case of transapical TAVI,
      in which the patient developed a false aneurysm at the apex of the left ventricle
      as a complication of the procedure.

PMID- 21073524
TI  - Vertebral artery dissection after iatrogenic cervical subcutaneous emphysema.
AB  - We report a case of spontaneous vertebral artery dissection (VAD) in a patient
      who developed extensive subcutaneous emphysema following the removal of a chest
      tube after a cardiac transplant. The pathophysiology and management of this
      uncommon complication are reviewed. Although vertebral and carotid artery
      dissections are unusual events occurring in 2.5 to 3 per 100,000 people, they are
      increasingly acknowledged to be important causes of stroke in the young and
      middle-aged adult population accounting for up to 25% of such cases. VADs are
      associated with a variety of minor traumatic mechanisms including painting a
      ceiling, yoga, chiropractic manipulation of the spine, and driving. These events
      cause injury to the vessel wall either by shearing forces secondary to rotational
      injuries or direct trauma to the vessel wall on bony prominences, especially the
      transverse processes of the cervical vertebrae. We present a case of a patient
      with documented previously normal vertebral arterial anatomy who developed a VAD
      after mediastinal tube removal resulted in subcutaneous emphysema tracking
      through fascial planes into his neck.

PMID- 21073525
TI  - Unusual case of tracheal injury after coronary revascularization.

PMID- 21073526
TI  - Excellent durability of a Starr-Edwards mitral caged-ball-valve prosthesis over
      34 years.

PMID- 21073527
TI  - Mycotic ascending aortic pseudoaneurysm following reduction aortoplasty.

PMID- 21073528
TI  - Giant primary cardiac synovial sarcoma.

PMID- 21073529
TI  - Anomalous origin of the left main coronary artery from the main pulmonary artery
      in an elderly patient.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      syndrome is an extremely rare diagnosis in elderly patients. We describe a 73
      year-old female with ALCAPA who underwent successful repair of this coronary
      anomaly.

PMID- 21073530
TI  - Intracardiac lipoma arising from the papillary muscle.
AB  - Cardiac lipoma is the commonest nonmyxomatous benign primary cardiac tumor. We
      report a case of lipoma arising from the anterolateral papillary muscle and
      presenting with a transient ischemic episode and a history of malignant melanoma.
      The lipoma was removed leaving the mitral apparatus intact. 

PMID- 21073531
TI  - Papillary muscle rupture: an unusual complication of chordal sparing mitral valve
      replacement.
AB  - An adult patient with advanced rheumatic heart disease undergoing chordal sparing
      mitral valve replacement as well as aortic valve replacement is presented. The
      patient developed an unusual complication of an infarction of the retained head
      of the anterolateral papillary muscle with subsequent spontaneous rupture 72
      hours postoperatively. The ruptured head of the papillary muscle was successfully
      resected via an aortotomy through the aortic valve prosthesis. The patient made
      an uneventful recovery. Care to avoid excessive tension on the preserved chordae
      during mitral valve replacement, especially in the setting of chronic rheumatic
      carditis, is stressed. 

PMID- 21073532
TI  - Primary benign interatrial schwannoma encountered during aortic valve
      replacement.
AB  - Primary neurogenic tumors of the heart are extremely uncommon. We report the
      resection of a benign primary schwannoma of the right atrium found incidentally
      during an aortic valve replacement. 

PMID- 21073533
TI  - Delayed sternal closure (DSC) after cardiac surgery: outcome and prognostic
      markers.
AB  - BACKGROUND: Maintenance of an open sternotomy (OS) after a complicated cardiac
      operation is an adjunct in the treatment of the severely impaired heart. The
      purpose of this retrospective study was to evaluate the incidence, survival, and
      predictors of poor outcome for open chest management (OCM) with delayed sternal
      closure (DSC) at our department. METHODS: Prolonged open chest (OC) was used in
      179 of 5122 cardiac surgery patients between 2004 and 2008 (3.5%). We wanted to
      determine indications, mortality, postoperative complications, and predictors of
      outcome. RESULTS: The incidence of OS was 3.5%, with 1.3% for isolated CABG, 2.4%
      for isolated valve, and 6.4% for combined procedures. Indications for OS were:
      hemodynamic compromise (110), intractable bleeding (19), arrhythmia (14), and
      cardiac edema or tamponade (36). 127 of the 179 patients with DSC (71%) survived.
      52 patients died: 20 before DSC and 32 after this procedure. Mortality could be
      related to the indication for OS: With the indication "low cardiac output
      syndrome" (LCOS) the mortality was 34.5%, for bleeding it was 26.3%, for
      arrhythmias, 21.4%, and for tamponade on closure it was 16.7%. After DSC, deep
      sternal wound infection occurred in nine patients (5%), superficial infection in
      4.7% of patients. There were 16 patients with postoperative stroke (8.9%) and 24
      patients with need for dialysis (13.4%). Predictors of mortality by univariate
      analysis were VAD insertion, new onset of hemodialysis, reoperation for bleeding,
      mean length of duration of OS (survivors 3.4 days, nonsurvivors 6.5 days), and
      longer duration of high-dose inotropic therapy. CONCLUSION: This study shows that
      OCM with DSC is a beneficial, therapeutic option in patients with postoperative
      LCOS, significant hemorrhage or intractable arrhythmias. However, patients with
      reoperation for bleeding, need for VAD, and particularly a prolonged delay before
      sternal closure continued to have a poor outcome. 

PMID- 21073534
TI  - Preoperative prediction of early mortality in patients with low ejection fraction
      undergoing coronary artery bypass grafting.
AB  - BACKGROUND AND AIM OF THE STUDY: Patients with low ejection fraction (EF)
      undergoing coronary artery bypass grafting (CABG) usually have a higher incidence
      of mortality and morbidity. In this retrospective study, we sought to detect
      significant preoperative predictors of early mortality in these patients.
      METHODS: Patients with an EF of <= 30% who underwent isolated CABG in Catharina
      Hospital, Eindhoven, the Netherlands, between January 1998 and December 2008 (n =
      413) were included in this study. All the preoperative patient-related risk
      factors were entered into a logistic regression analysis model to detect the
      significant predictors of early mortality. RESULTS: Patients with an EF of <= 30%
      represent 4.1% of the whole CABG population. The overall early mortality in this
      patient group was 9.1%. Risk factors for early mortality as identified by the
      univariate analysis were age, chronic obstructive pulmonary disease (COPD), prior
      CABG, New York Heart association (NYHA) class, emergency operation, preoperative
      serum creatinine (SeCr), and preoperative hemoglobin (Hb) level. These factors
      were entered into the multivariate analysis and were all identified as
      independent risk factors for early mortality. CONCLUSIONS: This study confirmed
      the impact of some well-known preoperative risk factors on early outcome in
      patients with low EF undergoing CABG. In addition, we have shown the predictive
      value of preoperative SeCr and hemoglobin level that have not yet been described.

PMID- 21073535
TI  - A modified technique for pulmonary valve replacement with a homograft.
AB  - We present a modified technique for replacement of the pulmonary valve with a
      pulmonary homograft. The principles of this technique are similar to the
      "scalloped subcoronary technique" for aortic valve replacement with a homograft.
      The advantages of using this technique in the pulmonary position are briefly
      discussed.

PMID- 21073536
TI  - Anthropometric estimation of femoral venous cannula length for cardiovascular
      surgery.
AB  - BACKGROUND: Femoral vein cannulation is an alternative method for central
      cannulation. However, no clinical guidelines have been established for optimal
      insertion length of femoral venous cannula. The purpose of the present study was
      to evaluate the correlation between the insertion length of femoral venous
      cannula (L), and the sum of the length from femoral artery (FA) puncture site to
      umbilicus (P-U) and the length from umbilicus to lower border of the sternum (U
      S) as an anthropometric estimation for adult patients undergoing cardiovascular
      surgery using femoral vein cannulation. We also attempted to determine the
      insertion length of femoral venous cannula by the patient's height and weight.
      METHODS: P-U and U-S were measured after anesthesia induction. L was measured
      after femoral venous cannula tip was positioned at the junction of inferior vena
      cava and right atrium using transesophageal echocardiography. The relationship
      between the sum of P-U and U-S (P-U-S), and L was analyzed by Pearson's
      correlation analysis. Bland-Altman analysis was used to compare the agreement
      between P-U-S and L. Multiple linear regression analysis was performed to
      identify the height and weight factors capable of predicting L. RESULTS: One
      hundred study patients were enrolled. P-U-S was highly correlated with L (r =
      0.95). The bias and precision were -2.60 +/- 8.57 mm. L was predicted from height
      and weight: L (mm) = 0.82 * height (cm) + 1.18 * weight (kg) + 188.46.
      CONCLUSIONS: P-U-S can be used as a reliable anthropometric estimation of L
      during adult cardiovascular surgery using femoral vein cannulation.

PMID- 21073537
TI  - Cancer stem cell immunophenotypes in oral squamous cell carcinoma.
AB  - BACKGROUND: The presence of cancer stem cell (CSC) antigens can be evidenced in
      some human tumors by phenotypic analysis through immunostaining. This study aims
      to identify a putative CSC immunophenotype in oral squamous cell carcinoma (OSCC)
      and determine its influence on prognosis. METHODS: The following data were
      retrieved from 157 patents: age, gender, primary anatomic site, smoking and
      alcohol intake, recurrence, metastases, histologic classification, treatment,
      disease-free survival (DFS), and overall survival (OS). An immunohistochemical
      study for CD44 and CD24 was performed in a tissue microarray of 157 paraffin
      blocks of OSCCs. RESULTS: In univariate analysis, the immunostaining pattern
      showed significant influences in relation to OS for alcohol intake and treatment,
      as well as for the CD44(+) and CD44(-) /CD24(-) immunophenotypes. The
      multivariate test confirmed these associations. CONCLUSIONS: Based on our
      results, the CD44 immunostaining and the absence of immunoexpression of these two
      investigated markers can be used in combination with other clinicopathologic
      information to improve the assessment of prognosis in OSCC.

PMID- 21073538
TI  - Endothelial cells of oral pyogenic granulomas express eNOS and CD105/endoglin: an
      immunohistochemical study.
AB  - BACKGROUND: The pyogenic granuloma (PG) is a common localized hyperplastic lesion
      of the oral cavity. The purpose of the present study was to investigate the
      immunohistochemical expression of endothelial nitric oxide synthases (eNOS) and
      CD105/endoglin in oral PGs, to evaluate their involvement in the angiogenetic
      pathways of the lesion. MATERIALS AND METHODS: Ninety-three PGs were included in
      the study. Sixteen tumors were further sub-classified as pregnancy tumors (PT)
      and seventeen as pyogenic granulomas with fibrosis (PGFM). Immunohistochemical
      expression of eNOS and CD105/endoglin was quantified by computerized image
      analysis with a semi-automated system. Percentage of staining and number of
      objects (positive vessels) were recorded for each case. RESULTS: Intense eNOS
      expression was seen in 92 of 93 lesions. A statistically significant association
      was found between eNOS percentage of staining/eNOS positive vascular spaces
      (objects) and age of the patients (9% increase per decade of life). Approximately
      40% less eNOS positive objects were recorded in PGFM compared with PGs. Intense
      membranous CD105/endoglin expression was seen in all cases. The percentage of
      CD105/endoglin staining was statistically increased in PGs compared with PT.
      Approximately 40% less CD105/endoglin objects were found in PGFM compared with
      PGs; 56% more CD105/endoglin objects were found in tongue lesions, compared with
      gingival lesions. There was no statistically significant correlation considering
      percentage of staining and number of objects between CD105/endoglin and eNOS.
      CONCLUSIONS: It is suggested that eNOS and CD105/endoglin are involved in the
      angiogenetic pathways of PG.

PMID- 21073539
TI  - Characterizing the relationship between sesame, coconut, and nut allergy in
      children.
AB  - Sesame and coconut are emerging food allergens in the United States. We sought to
      examine whether children allergic to peanuts and tree nuts are at increased risk
      of having an allergy to sesame or coconut. We performed a retrospective chart
      review of children who underwent skin prick testing (SPT) to sesame and coconut
      and identified 191 children who underwent SPT to sesame and 40 to coconut.
      Sensitization to sesame was more likely in children with positive SPT to peanuts
      (odds ratio [OR] = 6.7, 95% confidence interval [CI] [2.7-16.8], p < 0.001) and
      tree nuts (OR = 10.5, 95% CI [4.0-27.7], p < 0.001). Children with histories of
      both peanut and tree nut reaction were more likely to have a history of sesame
      reaction (OR = 10.2, 95% CI [2.7-38.7], p < 0.001). Children with sensitization
      or allergy to peanuts or tree nuts were not more likely to be sensitized or
      allergic to coconut. In conclusion, children with peanut or tree nut
      sensitization were more likely to be sensitized to sesame but not coconut.
      Children with clinical histories of both peanut and tree nut allergy were more
      likely to be allergic to sesame.

PMID- 21073540
TI  - Nasal nitric oxide levels in healthy pre-school children.
AB  - The evaluation of nasal nitric oxide (nNO) has been proposed as a screening tool
      in children with clinically suspectable primary ciliary dyskinesia. Nevertheless,
      normal values have been reported for school-aged children. This study was
      designed to identify normal nNO levels in pre-school children. nNO was assessed
      in 300 healthy children aged between 1.5 and 7.2. Two hundred and fifty of them
      were unable to fulfill the guideline requirements for nNO measurement and were
      assessed by sampling the nasal air continuously with a constant trans-nasal
      aspiration flow for 30 s during tidal breathing. For those children who were able
      to cooperate, the average nNO concentration was calculated according to
      guidelines. A statistically significant relationship between nNO level and age
      was demonstrated in this study group of pre-school children (p < 0.001). An
      increase in nNO of about 100 ppb was observed in children older than 6 yr vs.
      those aged < 3. This study presents a description of normal nNO values in pre
      school children. The effect of the age and the eventual presence of rhinitis and
      snoring need to be considered whenever nNO is evaluated in the clinical practice,
      in particular in non-cooperative children.

PMID- 21073541
TI  - Reduced iNOS expression in adenoids from children with otitis media with
      effusion.
AB  - Nitric oxide (NO) is a key mediator in the local immune response of human
      airways. Inducible NO-synthases (iNOS), and endothelial NO-synthases (eNOS) are
      two enzymes known to regulate its production. The role of NO in middle ear
      disease is not fully known. Previous studies suggest that NO might have a dual
      role, both promoting and suppressing middle ear inflammation. The aim of the
      present study was to compare the eNOS and iNOS expression in adenoids obtained
      from children with otitis media with effusion (OME) with the expression seen in
      adenoids derived from children without middle ear disease. In addition, the
      expression of IL-1beta and TNF-alpha were analyzed, because of their role in the
      iNOS-induction pathway. The iNOS and eNOS expression were analyzed with real-time
      PCR in 8 OME and 11 control adenoids. The corresponding proteins were
      demonstrated by immunohistochemical staining of adenoid tissue. A Luminex((r))
      assay was performed to analyze IL-1beta and TNF-alpha in nasopharyngeal secretion
      in 10 OME and 8 controls, and immunohistochemistry was performed on adenoid
      tissue and imprints from the adenoid surface. Children with OME exhibited lower
      levels of iNOS than controls without middle ear disease. No such difference was
      seen for eNOS. The corresponding proteins were found mainly in conjunction with
      surface epithelium. No significant changes were seen among the cytokines tested.
      The present results indicate that local induction of iNOS in adenoids might be of
      importance for preventing development of OME.

PMID- 21073542
TI  - Evidence for two independent functional variants for androgenetic alopecia around
      the androgen receptor gene.
AB  - The gene encoding the androgen receptor (AR) is associated with male pattern
      baldness (androgenetic alopecia - AGA). In case-control and family analyses, we
      mapped AR and the adjacent intergenic regions. We found evidence for association
      with two independent loci, one upstream and previously described and the other
      downstream and apparently novel. The haplotype comprising these SNPs was strongly
      associated with AGA (P = 3.75 * 10(-5)) in 1195 men. We also replicated
      association with a recently reported non-coding region on chromosome 20 and found
      that its association with AGA was less strong and independent of that of AR. Our
      results will help focus future efforts to further define AGA genetic risk.

PMID- 21073543
TI  - Immunological therapy in urological malignancy: novel combination strategies.
AB  - At present, immunotherapy in urological malignancy is experiencing a renaissance,
      particularly with the emergence of a host of innovative cancer vaccines. Herein,
      we will review promising immunotherapeutic approaches and evaluate the data
      supporting their inclusion in novel combination strategies.

PMID- 21073544
TI  - Plasmablastic lymphoma of the right testis.

PMID- 21073545
TI  - Nucleic acids of Enterococcus faecalis strain EC-12 are potent Toll-like receptor
      7 and 9 ligands inducing interleukin-12 production from murine splenocytes and
      murine macrophage cell line J774.1.
AB  - In experiment 1 of this study, the interleukin-12 (IL-12)-inducing ability of six
      Enterococcus strains was evaluated in comparison with that of five Lactobacillus
      strains using murine splenocytes. At the same time, the involvement of Toll-like
      receptor (TLR) ligands in IL-12-inducing ability was assessed using splenocytes
      from TLR2-, TLR4- and MyD88-deficient mice. Most Enterococcus strains, especially
      Enterococcus faecalis strain EC-12, exerted higher IL-12-inducing ability
      compared with the Lactobacillus strains evaluated. Almost the same amount of IL
      12 protein was produced by all lactic acid bacteria strains in splenocytes from
      TLR2- and TLR4-deficient mice, whereas splenocytes from MyD88-deficient mice
      showed no IL-12 production against all bacteria evaluated. In experiment 2, the
      role of TLR7, 8 and 9 ligands of E. faecalis strain EC-12 in the induction of IL
      12 production was evaluated using murine macrophage cell line J774.1. A drastic
      decrease in IL-12-inducing ability was observed when heat-killed E. faecalis
      strain EC-12 was treated with nuclease, particularly RNase. In addition, less
      than one-tenth of IL-12 was produced by heat-killed E. faecalis strain EC-12 when
      both TLR7 and 9 were antagonized. These facts indicate that the nucleic acids of
      E. faecalis strain EC-12, particularly its RNA, are the potent TLR7 and 9 ligands
      that induce IL-12 production from antigen-presenting cells.

PMID- 21073546
TI  - The calcineurin inhibitor RCAN1 is involved in cultured macrophage and in vivo
      immune response.
AB  - Studies on the role of regulator of calcineurin 1 (RCAN1) in immunity are
      limited, but have demonstrated an involvement in T-lymphocyte function. Here, we
      expand these studies to macrophages and in vivo infection. The treatment of RAW
      and primary mouse macrophages with lipopolysaccharide from Escherichia coli
      strongly induced RCAN1 isoform 4 (RCAN1-4), but not isoform 1. RCAN1-4 induction
      involved calcium, calcineurin, and reactive oxygen species. Subsequent analysis
      with whole bacteria including gram-negative E. coli and gram-positive
      Staphylococcus aureus revealed strong RCAN1-4 inductions by both, and where
      tested, dependence on calcium. Staphylococcus aureus cell wall components
      peptidoglycan and lipoteichoic acid also strongly induced RCAN1-4. In vivo, a
      significant induction in the proinflammatory cytokines monocyte chemotactic
      protein-1, interleukin-6, interferon-gamma, and tumor necrosis factor-alpha was
      observed in knockout (KO) lung vs. wild-type (WT) mice 7 days after nasal
      infection with Fransicella tularensis. This induction was not accompanied by a
      significant increase in F. tularensis burden in the KO lung. Additionally, a
      modest increase in respiratory burst activity in KO vs. WT macrophages was
      observed. Combined, these studies indicate that RCAN1 is involved in macrophage
      and the overall in vivo immune response, and provide additional evidence that
      RCAN1 plays an important role in cell immunity and infectious disease.

PMID- 21073547
TI  - Levofloxacin reduces inflammatory cytokine levels in human bronchial epithelia
      cells: implications for aerosol MP-376 (levofloxacin solution for inhalation)
      treatment of chronic pulmonary infections.
AB  - Inflammation resulting from chronic bacterial infection in the lung contributes
      to long-term pulmonary complications in chronic pulmonary infections such as
      cystic fibrosis. Aerosol administration of levofloxacin as in the form of the
      investigational formulation MP-376 results in higher concentrations in lung
      tissues that are higher than those that can be attained with oral or intravenous
      dosing of levofloxacin. The objective of this study was to evaluate the effect of
      high concentrations of levofloxacin achieved with aerosol administration of MP
      376 on proinflammatory cytokine secretion by immortalized human bronchial
      epithelia cells in vitro. Additionally, we investigated the potential mechanisms
      of the immunomodulatory effect of levofloxacin. In vitro studies in human lung
      epithelial cell lines showed that levofloxacin led to a dose-related reduction in
      IL-6 and IL-8 concentrations, with 300 MUg mL(-1) resulting in the reduction of
      levels of IL-6 by fourfold and IL-8 by twofold (P<0.05); in contrast, tobramycin
      increased IL-6 levels by 50%, but had no effect on IL-8. Levofloxacin treatment
      did not affect the cytokine mRNA level and nuclear factor-kappaB-dependent
      promoter activity. These findings suggest that high concentrations of
      levofloxacin obtained in pulmonary tissues following the administration of
      aerosol MP-376 may provide additional benefits in patients with chronic pulmonary
      infections that are independent of its antibacterial properties.

PMID- 21073548
TI  - Neural correlates of strategy use during auditory working memory in musicians and
      non-musicians.
AB  - Working memory (WM) performance in humans can be improved by structuring and
      organizing the material to be remembered. For visual and verbal information, this
      process of structuring has been associated with the involvement of a prefrontal
      parietal network, but for non-verbal auditory material, the brain areas that
      facilitate WM for structured information have remained elusive. Using functional
      magnetic resonance imaging, this study compared neural correlates underlying
      encoding and rehearsal of auditory WM for structured and unstructured material.
      Musicians and non-musicians performed a WM task on five-tone sequences that were
      either tonally structured (with all tones belonging to one tonal key) or tonally
      unstructured (atonal) sequences. Functional differences were observed for
      musicians (who are experts in the music domain), but not for non-musicians - The
      right pars orbitalis was activated more strongly in musicians during the encoding
      of unstructured (atonal) vs. structured (tonal) sequences. In addition, data for
      musicians showed that a lateral (pre)frontal-parietal network (including the
      right premotor cortex, right inferior precentral sulcus and left intraparietal
      sulcus) was activated during WM rehearsal of structured, as compared with
      unstructured, sequences. Our findings indicate that this network plays a role in
      strategy-based WM for non-verbal auditory information, corroborating previous
      results showing a similar network for strategy-based WM for visual and verbal
      information.

PMID- 21073550
TI  - Complementary distribution of glutamatergic cerebellar and GABAergic basal
      ganglia afferents to the rat motor thalamic nuclei.
AB  - Motor thalamic nuclei, ventral anterior (VA), ventral lateral (VL) and ventral
      medial (VM) nuclei, receive massive glutamatergic and GABAergic afferents from
      the cerebellum and basal ganglia, respectively. In the present study, these
      afferents were characterized with immunoreactivities for glutamic acid
      decarboxylase of 67 kDa (GAD67) and vesicular glutamate transporter (VGluT)2, and
      examined by combining immunocytochemistry with the anterograde axonal labeling
      and neuronal depletion methods in the rat brain. VGluT2 immunoreactivity was
      intense in the caudodorsal portion of the VA-VL, whereas GAD67 immunoreactivity
      was abundant in the VM and rostroventral portion of the VA-VL. The rostroventral
      VA-VL and VM contained two types of GAD67-immunopositive varicosities (large and
      small), but the caudodorsal VA-VL comprised small ones alone. VGluT2
      immunopositive varicosities were much larger in the caudodorsal VA-VL than those
      in the rostroventral VA-VL and VM. When anterograde tracers were injected into
      the basal ganglia output nuclei, the vast majority of labeled axon varicosities
      were large and distributed in the rostroventral VA-VL and VM, showing
      immunoreactivity for GAD67, but not for VGluT2. Only the large GAD67
      immunopositive varicosities were mostly abolished by kainic acid depletion of
      substantia nigra neurons. In contrast, large to giant axon varicosities derived
      from the deep cerebellar nuclei were distributed mostly in the caudodorsal VA-VL,
      displaying VGluT2 immunoreactivity. The VGluT2-positive varicosities disappeared
      from the core portion of the caudodorsal VA-VL by depletion of cerebellar nucleus
      neurons. Thus, complementary distributions of large VGluT2- and GAD67-positive
      terminals in the motor thalamic nuclei are considered to reflect glutamatergic
      cerebellar and GABAergic basal ganglia afferents, respectively.

PMID- 21073551
TI  - beta-Secretase activity in rat astrocytes: translational block of BACE1 and
      modulation of BACE2 expression.
AB  - BACE1 and BACE2 are two closely related membrane-bound aspartic proteases. BACE1
      is widely recognized as the neuronal beta-secretase that cleaves the amyloid-beta
      precursor protein, thus allowing the production of amyloid-beta, i.e. the peptide
      that has been proposed to trigger the neurodegenerative process in Alzheimer's
      disease. BACE2 has ubiquitous expression and its physiological and pathological
      role is still unclear. In light of a possible role of glial cells in the
      accumulation of amyloid-beta in brain, we have investigated the expression of
      these two enzymes in primary cultures of astrocytes. We show that astrocytes
      possess beta-secretase activity and produce amyloid-beta because of the activity
      of BACE2, but not BACE1, the expression of which is blocked at the translational
      level. Finally, our data demonstrate that changes in the astrocytic phenotype
      during neuroinflammation can produce both a negative as well as a positive
      modulation of beta-secretase activity, also depending on the differential
      responsivity of the brain regions.

PMID- 21073552
TI  - The Wnt /beta-catenin signaling pathway in the adult neurogenesis.
AB  - The Wnt/beta-catenin signaling pathway plays an important role in neural
      development, beta-catenin is a central component of the Wnt/beta-catenin
      signaling pathway, which not only performs the function of transmitting
      information in the cytoplasm, but also translocates to the nucleus-activating
      target gene transcription. The target genes in neural tissues have not been fully
      revealed, but the effects of the Wnt/beta-catenin signaling pathway in adult
      neurogenesis have been demonstrated by ongoing research, which are significative
      to the basic research and treatment of neuronal degeneration diseases. Here, we
      review key findings to show the characteristics of beta-catenin and its pivotal
      nature in the Wnt/beta-catenin signaling pathway in a number of molecular
      studies. We also review current literature on the role of beta-catenin in adult
      neurogenesis, which consists of an active process encompassing the proliferation,
      migration, differentiation and final synaptogenesis.

PMID- 21073549
TI  - Quantitative localisation of synaptic and extrasynaptic GABAA receptor subunits
      on hippocampal pyramidal cells by freeze-fracture replica immunolabelling.
AB  - Hippocampal CA1 pyramidal cells, which receive gamma-aminobutyric acid
      (GABA)ergic input from at least 18 types of presynaptic neuron, express 14
      subunits of the pentameric GABA(A) receptor. The relative contribution of any
      subunit to synaptic and extrasynaptic receptors influences the dynamics of GABA
      and drug actions. Synaptic receptors mediate phasic GABA-evoked conductance and
      extrasynaptic receptors contribute to a tonic conductance. We used freeze
      fracture replica-immunogold labelling, a sensitive quantitative
      immunocytochemical method, to detect synaptic and extrasynaptic pools of the
      alpha1, alpha2 and beta3 subunits. Antibodies to the cytoplasmic loop of the
      subunits showed immunogold particles concentrated on distinct clusters of
      intramembrane particles (IMPs) on the cytoplasmic face of the plasma membrane on
      the somata, dendrites and axon initial segments, with an abrupt decrease in
      labelling at the edge of the IMP cluster. Neuroligin-2, a GABAergic synapse
      specific adhesion molecule, co-labels all beta3 subunit-rich IMP clusters,
      therefore we considered them synapses. Double-labelling for two subunits showed
      that virtually all somatic synapses contain the alpha1, alpha2 and beta3
      subunits. The extrasynaptic plasma membrane of the somata, dendrites and
      dendritic spines showed low-density immunolabelling. Synaptic labelling densities
      on somata for the alpha1, alpha2 and beta3 subunits were 78-132, 94 and 79 times
      higher than on the extrasynaptic membranes, respectively. As GABAergic synapses
      occupy 0.72% of the soma surface, the fraction of synaptic labelling was 33-48
      (alpha1), 40 (alpha2) and 36 (beta3)% of the total somatic surface
      immunolabelling. Assuming similar antibody access to all receptors, about 60% of
      these subunits are in extrasynaptic receptors.

PMID- 21073553
TI  - Excessive novelty-induced c-Fos expression and altered neurogenesis in the
      hippocampus of GluA1 knockout mice.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1
      subunit-deficient (GluA1-/-) mice display novelty-induced hyperactivity,
      cognitive and social defects and may model psychiatric disorders, such as
      schizophrenia and depression/mania. We used c-Fos expression in GluA1-/- mice to
      identify brain regions responsible for novelty-induced hyperlocomotion. Exposure
      to a novel cage for 2 h significantly increased c-Fos expression in many brain
      regions in both wild-type and knockout mice. Interestingly, the clearest genotype
      effect was observed in the hippocampus and its main input region, the entorhinal
      cortex, where the novelty-induced c-Fos expression was more strongly enhanced in
      GluA1-/- mice. Their novelty-induced hyperlocomotion partly depended on the
      activity of AMPA receptors, as it was diminished by the AMPA receptor antagonist
      2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX) and
      unaffected by the AMPA receptor potentiator 2,3-dihydro-1,4-benzodioxin-6-yl-1
      piperidinylmethanone (CX546). The hyperlocomotion of GluA1-/- mice was normalised
      to the level of wild-type mice within 5-6 h, after which their locomotion
      followed normal circadian rhythm and was not affected by acute or chronic
      treatments with the selective serotonin reuptake inhibitor escitalopram. We
      propose that hippocampal dysfunction, as evidenced by the excessive c-Fos
      response to novelty, is the major contributor to novelty-induced hyperlocomotion
      in GluA1-/- mice. Hippocampal dysfunction was also indicated by changes in
      proliferation and survival of adult-born dentate gyrus cells in the knockout
      mice. These results suggest focusing on the functions of hippocampal formation,
      such as novelty detection, when using the GluA1-/- mouse line as a model for
      neuropsychiatric and cognitive disorders.

PMID- 21073554
TI  - The role of the bed nucleus of the stria terminalis in stress-induced inhibition
      of pulsatile luteinising hormone secretion in the female rat.
AB  - The bed nucleus of the stria terminalis (BNST) occupies a central position in the
      neural circuitry regulating the hypothalamic-pituitary-adrenocortical axis
      response to stress. The potential role of the BNST in stress-induced suppression
      of the gondotrophin-releasing hormone (GnRH) pulse generator, the central
      regulator of the reproductive system, was assessed by examining the effects of
      micro-infusion of corticotrophin-releasing factor (CRF) or its antagonist into
      the BNST on pulsatile luteinising hormone (LH) secretion or stress-induced
      inhibition of LH pulses, respectively. Ovariectomised oestrogen-treated rats were
      implanted chronically with bilateral cannulae in the dorsolateral BNST and i.v.
      catheters. CRF (25, 50 or 100 pmol in 200 nl of artificial cerebrospinal fluid)
      administered bilaterally into the BNST resulted in a dose-dependent decrease in
      LH pulse frequency, and induced Fos expression in glutamic acid decarboxylase
      immunostained neurones in the medial preoptic area. These results suggest that
      the activation of hypothalamic GABAergic neurones in response to intra-BNST
      administration of CRF may be involved in the suppression of LH pulses.
      Furthermore, administration of CRF antagonist (280 pmol astressin-B, three times
      at 20-min intervals) into the BNST effectively blocked the suppression of
      pulsatile LH secretion in response to restraint (1 h) but not hypoglycaemic (0.25
      U insulin/kg, i.v.) stress. These data suggest that CRF innervation of the
      dorsolateral BNST plays a key, but differential, role in stress-induced
      suppression of the GnRH pulse generator.

PMID- 21073555
TI  - Evidence that RF-amide related peptide-3 is not a mediator of the inhibitory
      effects of psychosocial stress on gonadotrophin secretion in ovariectomised ewes.
AB  - It is well known that stress inhibits normal reproductive function, including
      gonadotrophin secretion; however, the mechanisms and mediators involved are
      largely unknown. Stress impairs the secretion of luteinising hormone (LH), and it
      has been suggested that the RF-amide gonadotrophin-inhibitory hormone (GnIH),
      known as RF-amide related peptide-3 (RFRP-3) in mammalian species, may mediate
      this inhibitory effect of stress. If this is the case, the GnIH/RFRP system would
      likely be up-regulated during stress. We tested this hypothesis in ovariectomised
      ewes using a psychosocial stressor: isolation/restraint. Ewes were randomly
      allocated to control or stress (n=5 per group). Isolation/restraint stress was
      imposed for 90 min after control sampling for 4 h, whereas control ewes were
      sampled continuously for 5.5 h. All ewes were then euthanased and brains were
      collected. As expected, plasma concentrations of cortisol were increased
      significantly (P<0.05) by stress and plasma concentrations of LH were
      significantly (P<0.05) reduced. Immunohistochemistry and in situ hybridisation
      were conducted for RFRP-3 peptide and RFRP mRNA expression, respectively, in the
      paraventricular nucleus/dorsal medial hypothalamus region of the hypothalamus.
      There was no significant effect of stress on RFRP-3 peptide or mRNA levels, with
      no differences between control or stress ewes. Furthermore, there was no
      difference in the number of RFRP-3 cells double-labelled for Fos between control
      and stress ewes and there was no difference in the cellular expression of RFRP
      mRNA between groups. These results indicate that the GnIH/RFRP system is not
      activated by psychosocial stress in ewes, suggesting that it is an unlikely
      mediator of the effects of stress on LH secretion.

PMID- 21073556
TI  - Antiplatelet drug interactions.
AB  - Both laboratory studies in healthy volunteers and clinical studies have suggested
      adverse interactions between antiplatelet drugs and other commonly used
      medications. Interactions described include those between aspirin and ibuprofen,
      aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and the
      thienopyridine, clopidogrel, and drugs inhibiting CYP2C19, notably the proton
      pump inhibitors (PPI) omeprazole and esomeprazole. Other interactions between
      thienopyridines and CYP3A4/5 have also been reported for statins and calcium
      channel blockers. The ibuprofen/aspirin interaction is thought to be caused by
      ibuprofen blocking the access of aspirin to platelet cyclo-oxygenase. The
      thienopyridine interactions are caused by inhibition of microsomal enzymes that
      metabolize these pro-drugs to their active metabolites. We review the evidence
      for these interactions, assess their clinical importance and suggest strategies
      of how to deal with them in clinical practice. We conclude that ibuprofen is
      likely to interact with aspirin and reduce its anti-platelet action particularly
      in those patients who take ibuprofen chronically. This interaction is of greater
      relevance to those patients at high cardiovascular risk. A sensible strategy is
      to advise users of aspirin to avoid chronic ibuprofen or to ingest aspirin at
      least 2 h prior to ibuprofen. Clearly the use of NSAIDs that do not interact in
      this way is preferred. For the clopidogrel CYP2C19 and CYP3A4/5 interactions,
      there is good evidence that these interactions occur. However, there is less good
      evidence to support the clinical importance of these interactions. Again, a
      reasonable strategy is to avoid the chronic use of drugs that inhibit CYP2C19,
      notably PPIs, in subjects taking clopidogrel and use high dose H2 antagonists
      instead. Finally, anti-platelet agents probably interact with other drugs that
      affect platelet function such as selective serotonin reuptake inhibitors, and
      clinicians should probably judge patients taking such combination therapies as at
      high risk for bleeding.

PMID- 21073557
TI  - Historical perspectives: drug interactions - it all began with cheese.

PMID- 21073558
TI  - Drug-drug interactions in the treatment of HIV infection: focus on
      pharmacokinetic enhancement through CYP3A inhibition.
AB  - The aim of this review is to discuss the effect of pharmacokinetic drug-drug
      interactions (DDIs) in the antiretroviral treatment of HIV infection. In
      particular, but not exclusively, DDIs due to the cytochrome P450 3A (CYP3A)
      inhibitor ritonavir, which is used to increase antiretroviral drug exposure - a
      technique known as pharmacokinetic enhancement or 'ritonavir boosting'- will be
      reviewed. The emphasis here will be on the treatment of important co-morbidities
      common in patients with HIV, including dyslipidaemia, hypertension, tuberculosis
      and opiate dependence, as well as on the potentially life-threatening interaction
      between ritonavir and inhalational steroids, and on the effect of acid-reducing
      agents on some antiretroviral drugs. Finally, further developments with regard to
      the use of CYP3A-blocking agents to augment the efficacy of antiviral therapy
      will be discussed.

PMID- 21073559
TI  - Expression of fatty acid-binding protein 4/aP2 is correlated with plaque
      instability in carotid atherosclerosis.
AB  - OBJECTIVE: the molecular basis for atherosclerotic plaque vulnerability with high
      risk of plaque rupture and thromboembolism is complex. We investigated whether
      clinical estimates of plaque stability correlate with differentially expressed
      mRNA transcripts within the lesion. METHODS AND RESULTS: endarterectomy samples
      from patients undergoing surgery for symptomatic and asymptomatic carotid
      stenosis were prospectively collected and clinical parameters recorded in the
      Biobank of Karolinska Carotid Endarterectomies. mRNA expression profiling (n =
      40) and quantitative RT-PCR (n = 105) revealed increased levels of fatty acid
      binding protein 4 (FABP4/aP2) in lesions from patients with recent symptoms of
      plaque instability compared to asymptomatic patients (array: FC = 2, P < 0.05; RT
      PCR: P < 0.05). At the mRNA level, FABP4/aP2 correlated with the cell markers
      CD36, CD68 and CD163 of monocyte/macrophage lineage as well as with CD4-positive
      T cells. FABP4/aP2 mRNA expression was also correlated with enzymes of the
      leukotriene pathway, 5-lipoxygenase and leukotriene A4 hydrolase. In addition,
      analysis of transcript profiles identified CD52 and adipophilin as the mRNAs with
      the highest correlation with FABP4/aP2. Expression of FABP4/aP2 by macrophages
      and CD52 by T cells in the lesion was confirmed by immunohistochemistry.
      CONCLUSIONS: expression of FABP4/aP2 is increased at the mRNA level in unstable
      carotid plaques. Immunohistochemical analyses showed localization of FABP4/aP2 to
      macrophage populations. These FABP4/aP2-positive macrophages constitute an
      important and prevalent phenotype and could provide a new link between scavenging
      mediated lipid uptake and cellular metabolic stress in plaque. In addition
      FABP4/aP2 correlates with other important signs of inflammation and plaque
      instability, such as T cells and leukotriene enzymes. Taken together, these
      results indicate that FABP4/aP2 is a key factor connecting vascular and cellular
      lipid accumulation to inflammation.

PMID- 21073561
TI  - Positive working relationships matter for better nurse and patient outcomes.

PMID- 21073560
TI  - Fatigue severity remains stable over time and independently associated with
      orthostatic symptoms in chronic fatigue syndrome: a longitudinal study.
AB  - OBJECTIVES: to examine fatigue variability over time in chronic fatigue syndrome
      (CFS) and the effect of other symptoms on its predictability. DESIGN:
      longitudinal cohort study of patients with CFS (Fukuda criteria). SETTING:
      specialist CFS clinical service. SUBJECTS: phase 1: 100 patients who participated
      in a study of CFS symptoms in 2005 were revisited in 2009. Phase 2: 25 patients
      completed fatigue diaries to address intra- and inter-day variability in
      perceived fatigue. MAIN OUTCOME MEASURES: phase 1: subjects completed fatigue
      impact scale (FIS), Epworth sleepiness scale (ESS), orthostatic grading scale
      (OGS) and hospital anxiety and depression scale (HADS). Changes in variables
      represented the differences between 2005 and 2009. Phase 2: subjects rated
      fatigue on a scale of 0 (no fatigue) to 10 (severe fatigue) four times a day for
      5 weeks. RESULTS: symptom assessment tools were available in both 2005 and 2009
      for 74% of patients. FIS and HADS depression (HAD-D) and anxiety (HAD-A) scores
      significantly improved during follow-up whereas ESS and OGS remained stable. FIS
      improved in 29/74 (39%) subjects, and by >= 10 points in 19 (26%). FIS worsened
      by >= 10 points in 33/74 (45%) subjects. On multivariate analysis, independent
      predictors of current fatigue (FIS in 2009) were FIS in 2005, HAD-D in 2009, OGS
      in 2009 and change in HAD-A. Reported fatigue was stable from week to week and
      from day to day. Patients reported higher fatigue in the morning (mean +/- SD;
      6.4 +/- 2), becoming significantly lower at lunchtime (6.2 +/- 2; P < 0.05) and
      increasing again to 7 +/- 2 at bedtime. CONCLUSIONS: current fatigue is
      independently associated with current autonomic symptom burden, current
      depression and change in anxiety during follow-up. These findings have
      implications for targeted symptom management in CFS.

PMID- 21073562
TI  - When respect deteriorates: incivility as a moderator of the stressor-strain
      relationship among hospital workers.
AB  - AIM: To test whether incivility at work exacerbates the relationship between
      stressors and strain for hospital workers. BACKGROUND: A climate of incivility
      and disrespect among colleagues was expected to heighten the impact of work
      stressors on the mental and physical health of care providers. METHODS: Members
      of 17 care-providing units from five hospital systems in Canada completed
      surveys, before and after a civility intervention (eight intervention vs. nine
      comparison units). Analyses tested whether (1) incivility moderated the stressor
      strain relationship at baseline (n=478), and (2) the stressor-strain relationship
      decreased for the intervention units relative to comparison units 6 months later
      (n=361). RESULTS: (1) Pre-intervention, individuals reporting more incivility on
      their unit showed a stronger stressor-strain relationship. (2) The negative
      relationship between work overload and mental health was mitigated among
      intervention group staff 6 months after the introduction of a colleague-based
      civility programme. CONCLUSIONS: Besides being a stressor itself, incivility
      exacerbates the relationship between existing job role stressors and strain among
      health care workers. IMPLICATIONS FOR NURSING MANAGEMENT: Colleague civility and
      respect have an important ripple effect of buffering inevitable work stressors,
      helping health care providers respond to stress with greater health and
      resiliency.

PMID- 21073563
TI  - Authentic leadership and nurses' voice behaviour and perceptions of care quality.
AB  - AIM: The purpose of the present study was to test a theoretical model linking
      authentic leadership with staff nurses' trust in their manager, work engagement,
      voice behaviour and perceived unit care quality. BACKGROUND: Authentic leadership
      is a guide for effective leadership needed to build trust and healthier work
      environments because there is special attention given to honesty, integrity and
      high ethical standards in the development of leader-follower relationships.
      METHODS: A non-experimental, predictive survey design was used to test the
      hypothesized model in a random sample of 280 (48% response rate) registered
      nurses working in acute care hospitals in Ontario. RESULTS: The final model
      fitted the data acceptably (chi(2)=17.24, d.f.=11, P=0.10, IFI=0.99, CFI=0.99,
      RMSEA=0.045). Authentic leadership significantly and positively influenced staff
      nurses' trust in their manager and work engagement which in turn predicted voice
      behaviour and perceived unit care quality. CONCLUSIONS: These findings suggest
      that authentic leadership and trust in the manager play a role in fostering
      trust, work engagement, voice behaviour and perceived quality of care.
      IMPLICATIONS FOR NURSING MANAGEMENT: Nursing leaders can improve care quality and
      workplace conditions by paying attention to facilitating genuine and positive
      relationships with their staff.

PMID- 21073564
TI  - Effects of work environments on nurse and patient outcomes.
AB  - AIM: To determine the relationship between nurses' perceptions of their work
      environment and quality/risk outcomes for patients and nurses in acute care
      settings. BACKGROUND: Nurses are leaving the profession as a result of high
      levels of job dissatisfaction arising from current working conditions. To gain
      organizational support for workplace improvements, evidence is needed to
      demonstrate the impact of the work environment on patient care. METHOD: A multi
      level design was used to collect data from nurses (n=679) and patients (n=1005)
      within 61 medical and surgical units in 21 hospitals in Canada. RESULTS: Using
      multilevel structural equation modelling, the hypothesized model fitted well with
      the data [chi(2)=21.074, d.f.=10, Comparative Fit Index (CFI)=0.985, Tucker-Lewis
      Index (TLI)=0.921, Root Mean Square Error of Approximation (RMSEA)=0.041,
      Standardized Root Mean Square Residual (SRMR) 0.002 (within) and 0.054
      (between)]. Empowering workplaces had positive effects on nurse-assessed quality
      of care and predicted fewer falls and nurse-assessed risks as mediated through
      group processes. These conditions positively impacted individual psychological
      empowerment which, in turn, had significant direct effects on empowered
      behaviour, job satisfaction and care quality. CONCLUSIONS: Empowered workplaces
      support positive outcomes for both nurses and patients. IMPLICATIONS FOR NURSING
      MANAGEMENT: Managers employing strategies to create more empowered workplaces
      have the potential to improve nursing teamwork that supports higher quality care,
      less patient risk and more satisfied nurses.

PMID- 21073565
TI  - The link between leadership and safety outcomes in hospitals.
AB  - AIM: To test and refine a model examining relationships among leadership,
      interactional justice, quality of the nursing work environment, safety climate
      and patient and nurse safety outcomes. BACKGROUND: The quality of nursing work
      environments may pose serious threats to patient and nurse safety. Justice is an
      important element in work environments that support safety initiatives yet little
      research has been done that looks at how leader interactional justice influences
      safety outcomes. METHOD: A cross-sectional survey was conducted with 600 acute
      care registered nurses (RNs) to test and refine a model linking interactional
      justice, the quality of nurse leader-nurse relationships, work environment and
      safety climate with patient and nurse outcomes. RESULTS: In general the
      hypothesized model was supported. Resonant leadership and interactional justice
      influenced the quality of the leader-nurse relationship which in turn affected
      the quality of the work environment and safety climate. This ultimately was
      associated with decreased reported medication errors, intentions to leave and
      emotional exhaustion. CONCLUSIONS: Quality relationships based on fairness and
      empathy play a pivotal role in creating positive safety climates and work
      environments. IMPLICATIONS FOR NURSING MANAGEMENT: To advocate for safe work
      environments, managers must strive to develop high-quality relationships through
      just leadership practices.

PMID- 21073566
TI  - Relational coordination among nurses and other providers: impact on the quality
      of patient care.
AB  - AIM: The present study examined nurse reports of relational coordination between
      nurses and other providers and the impact of relational coordination on patient
      care quality. BACKGROUND: While communication between providers has been
      traditionally considered important to improve quality, relational coordination
      extends this view, emphasising the value of high-quality relationships
      exemplified by shared goals, shared knowledge and mutual respect; and high
      quality communication that is timely, frequent, accurate and problem-solving.
      METHODS: Direct care registered nurses (RNs) (n=747) completed surveys to assess
      relational coordination across five provider functions and six types of patient
      care units. Nurses also reported perceptions about patient care quality. RESULTS:
      In all analyses, relational coordination between nurses and other providers was
      significantly related to overall quality, in the expected directions. As
      relational coordination increased, nurses reported decreases in adverse events
      such as hospital-acquired infections and medication errors. CONCLUSIONS:
      Enhancing relational coordination between nurses and other providers is central
      to improving the quality of patient care. IMPLICATIONS FOR NURSE MANAGERS AND NEW
      KNOWLEDGE: The emerging theory of relational coordination provides a useful new
      research-based framework for managers to use to improve provider relationships,
      communication and the quality of care.

PMID- 21073567
TI  - Nursing staff teamwork and job satisfaction.
AB  - AIM: The aim of the present study was to explore the influence of unit
      characteristics, staff characteristics and teamwork on job satisfaction with
      current position and occupation. BACKGROUND: Teamwork has been associated with a
      higher level of job satisfaction but few studies have focused on the acute care
      inpatient hospital nursing team. METHODS: This was a cross-sectional study with a
      sample of 3675 nursing staff from five hospitals and 80 patient care units.
      Participants completed the Nursing Teamwork Survey (NTS). RESULTS: Participants'
      levels of job satisfaction with current position and satisfaction with occupation
      were both higher when they rated their teamwork higher (P<0.001) and perceived
      their staffing as adequate more often (P<0.001). Type of unit influenced both
      satisfaction variables (P<0.05). Additionally, education, gender and job title
      influenced satisfaction with occupation (P<0.05) but not with current position.
      CONCLUSIONS: Results of this present study demonstrate that within nursing teams
      on acute care patient units, a higher level of teamwork and perceptions of
      adequate staffing leads to greater job satisfaction with current position and
      occupation. IMPLICATIONS FOR NURSING MANAGEMENT: Findings suggest that efforts to
      improve teamwork and ensure adequate staffing in acute care settings would have a
      major impact on staff satisfaction.

PMID- 21073568
TI  - Beyond generational differences: a literature review of the impact of relational
      diversity on nurses' attitudes and work.
AB  - AIM: Based on a review of the empirical literature, we examine the influence of
      selected diversity attributes on nurses' work-related attitudes and behaviour.
      BACKGROUND: The nursing workforce has become increasingly heterogeneous in its
      age, educational attainment, and ethnicity/race distributions. There is
      considerable speculation, in the literature, that the work values of recent
      nursing graduates are discordant with more experienced nurses. RESULTS: A review
      of studies published between 1980 and 2009 in nursing, healthcare, psychology,
      and organizational behaviour led to the inclusion of 19 peer-reviewed research
      articles, from which our analyses are drawn. KEY ISSUES: The findings indicate
      that age diversity leads to negative behaviour toward others in the workgroup
      (e.g. poor collegial relationships) whereas perceived work-values diversity is
      negatively associated with individuals' own attitudes and behaviour toward their
      work as well as toward other members of their workgroup. CONCLUSIONS: There is
      inconclusive evidence about the attributes that most significantly influence
      nurses' attitudes and work; however, preliminary evidence supports the salience
      of work values. IMPLICATIONS FOR NURSING MANAGEMENT: Irrespective of the actual
      diversity within workgroups, how nurses see one another can have a significant
      impact on members of their workgroups and their functioning. Broader
      conceptualizations of diversity are necessary.

PMID- 21073569
TI  - Generational differences in distress, attitudes and incivility among nurses.
AB  - AIMS: The first research objective was to replicate the finding of Leiter et al.
      [(2008)Journal of Nursing Management, 16, 100-109.] of Generation X nurses
      (n=338) reporting higher levels of distress than Baby Boomer nurses (n=139). The
      second objective was to test whether Generation X nurses reported more negative
      social environments at work than did Baby Boomer nurses. BACKGROUND: Negative
      social environments can influence the quality of work and the experience of
      distress for nurses. Generational differences in the experience of distress and
      collegiality have implications for the establishment of healthy workplaces,
      recruitment and retention. METHODS: A questionnaire survey of nurses was
      organized by generation. Analyses of variance contrasted the scores on burnout,
      turnover intention, physical symptoms, supervisor incivility, coworker incivility
      and team civility. RESULTS: The results confirmed the hypotheses of Generation X
      nurses reporting more negative experiences than did Baby Boomer nurses on all
      measures. CONCLUSIONS: The negative quality of social encounters at work
      contributes to nurses' experience of distress and suggest conflicts of values
      with the dominant culture of their workplaces. IMPLICATIONS FOR NURSING
      MANAGEMENT: Proactive initiatives to enhance the quality of collegiality can
      contribute to retention strategies. Building collegiality across generations can
      be especially useful.

PMID- 21073570
TI  - Antecedents and consequences of intra-group conflict among nurses.
AB  - AIM: To test a theoretical model linking selected antecedent variables to intra
      group conflict among nurses, and subsequently conflict management style, job
      stress and job satisfaction. BACKGROUND: A contributing factor to the nursing
      shortage is job dissatisfaction as a result of conflict among nurses. To develop
      strategies to reduce conflict, research is needed to understand the causes and
      outcomes of conflict in nursing work environments. METHOD: A predictive, non
      experimental design was used in a random sample of 277 acute care nurses.
      Structural equation modelling was used to analyse the hypothesised model.
      RESULTS: Nurses' core self-evaluations, complexity of care and relationships with
      managers and nursing colleagues influenced their perceived level of conflict.
      Conflict management style partially mediated the relationship between conflict
      and job satisfaction. Job stress had a direct effect on job satisfaction and core
      self-evaluation had a direct effect on job stress. CONCLUSION: Conflict and its
      associated outcomes is a complex process, affected by dispositional, contextual
      and interpersonal factors. How nurses manage conflict may not prevent the
      negative effects of conflict, however, learning to manage conflict using
      collaboration and accommodation may help nurses experience greater job
      satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: Strategies to manage and
      reduce conflict include building interactional justice practices and positive
      interpersonal relationships.

PMID- 21073571
TI  - Authentic leadership of preceptors: predictor of new graduate nurses' work
      engagement and job satisfaction.
AB  - AIM: To examine the relationships between new graduate nurses' perceptions of
      preceptor authentic leadership, work engagement and job satisfaction. BACKGROUND:
      During a time when the retention of new graduate nurses is of the upmost
      importance, the reliance on preceptors to facilitate the transition of new
      graduate nurses is paramount. METHODS: A predictive non-experimental survey
      design was used to examine the relationships between study variables. The final
      sample consisted of 170 randomly selected Registered Nurses (RNs) with <3 years
      experience and who worked in an acute care setting. RESULTS: Hierarchical
      multiple regression demonstrated that 20% of the variance in job satisfaction was
      explained by authentic leadership and work engagement. Furthermore, work
      engagement was found to partially mediate the relationship between authentic
      leadership of preceptors and engagement of new graduate nurses. CONCLUSIONS: New
      graduate nurses paired with preceptors who demonstrate high levels of authentic
      leadership feel more engaged and are more satisfied. Engagement is an important
      mechanism by which authentic leadership affects job satisfaction. IMPLICATIONS
      FOR NURSING MANAGEMENT: Managers must be aware of the role preceptors' authentic
      leadership plays in promoting work engagement and job satisfaction of new nurses.

PMID- 21073572
TI  - Effects of workplace incivility and empowerment on newly-graduated nurses'
      organizational commitment.
AB  - AIM: The purpose of the present study was to test an expanded model of Kanter's
      theory by examining the influence of structural empowerment, psychological
      empowerment and workplace incivility on the organizational commitment of newly
      graduated nurses. BACKGROUND: The first years of practise represent an important
      confidence-building phase for newly-graduated nurses, yet many new nurses are
      exposed to disempowering experiences and incivility in the workplace. METHOD: A
      predictive non-experimental design was used to examine the impact of structural
      empowerment, psychological empowerment and workplace incivility on the affective
      commitment of newly-graduated nurses (n=117) working in acute care hospitals.
      RESULTS: Controlling for age, 23.1% of the variance in affective commitment was
      explained by structural empowerment, psychological empowerment and workplace
      incivility [R2=0.231, F(5,107) =6.43, P=0.000]. Access to opportunity was the
      most empowering factor, with access to support and formal power perceived as
      least empowering. Perceived co-worker incivility was greater than perceived
      supervisor incivility. CONCLUSION: Results offer significant support for the use
      of Kanter's theory in the newly-graduated nurse population. IMPLICATIONS FOR
      NURSING MANAGEMENT: Without specific strategies in place to combat incivility and
      disempowerment in the workplace, attempts to prevent further organizational
      attrition of new members may be futile.

PMID- 21073573
TI  - Transforming work place relationships through shared decision making.
AB  - AIM: Using Donabedian's Structure-Process-Outcomes (SPO) paradigm, this study
      explored the SPO linkages related to nurse-nurse leader shared decision making
      around workload issues, such as safe staffing assignments. BACKGROUND: Shared
      decision making represents nurses' control over practice, which is associated
      with positive nurse outcomes, such as job satisfaction. This study is based upon
      four project sites where nurse-led project teams addressed workload issues.
      METHODS: Participatory action research was used, with the authors acting as
      participant observers. Four sites were case ordered and analysed: least
      successful to most successful outcomes. Cross-case matrices were constructed to
      identify SPO linkages. Data included observation field notes, interviews and
      focus groups. RESULTS: Operations leaders with formal access to empowerment
      structures, such as information and resources, were the critical link to
      successful outcomes. Sites with conflict that blocked team-operations leader
      relationships were unable to engage in effective, sustainable decision making.
      CONCLUSIONS: Effective work relationships among teams consisting of staff and
      front-line leaders contributed to successful outcomes, but team-operations leader
      relationships made the biggest difference. IMPLICATIONS FOR NURSING MANAGEMENT:
      Formal access to power through leadership is critical for building and sustaining
      processes that promote and sustain nurses' control over practice.

PMID- 21073574
TI  - Impact of leadership development on emotional health in healthcare managers.
AB  - AIM: To examine the effects of a Leadership Development Initiative (LDI) on the
      emotional health and well-being among five levels of healthcare managers.
      BACKGROUND: Increasingly dynamic, demanding healthcare environments result in
      highly stressful work atmospheres. METHODS: Using quasi-experimental and mixed
      methods, we used regression on pre- and post-LDI survey data with 86 managers,
      and individual/focus group interview data for focused ethnographic analysis.
      RESULTS: An increasing trend was observed in self-assessed leadership practices
      after the LDI with a significant increase in 'inspiring a shared vision'
      (P<0.01). However, a non-significant decreasing trend in areas of work life and a
      non-significant increase in cynicism (P=0.14) was observed. Before the LDI,
      participants' self-assessment of their practice to 'enable others to act' was
      negatively related to emotional exhaustion (P<0.01). Both before and after the
      LDI, 'modelling the way' was significantly related to professional efficacy
      (P<0.01 pre; P<0.05 post). Post-LDI, 'inspiring a shared vision' was negatively
      (P<0.01) and 'enabling others to act' was positively (P<0.05) related to
      cynicism. CONCLUSION: The LDI provided opportunities for healthcare managers to
      connect, strengthen leadership and social support networks and manage burnout.
      IMPLICATIONS FOR NURSING MANAGEMENT: Transformational leadership practices may
      influence managers' emotional health. Senior administrative support and
      communicating the structure and vision of developmental initiatives may help to
      achieve realistic expectations.

PMID- 21073575
TI  - Going blank: factors contributing to interruptions to nurses' work and related
      outcomes.
AB  - AIM: To examine interruptions to nurses' work, the systems issues related to
      these and the associated outcomes. BACKGROUND: While some research has described
      the role interruptions play in medication errors, work is needed to examine
      specific factors in the nursing work environment that cause interruptions and to
      assess the impact of these on nurses' work and patient outcomes. METHODS: The
      present study utilized a mixed method design that involved work observation to
      detect nursing interruptions in the workplace followed by focus groups with a
      subsample of nurses. RESULTS: A total of 13,025 interruptions were observed.
      Equal numbers of these took place on medical and surgical units. The predominant
      source of interruptions was members of the health team, who interrupted more
      frequently on medical units. CONCLUSIONS: Differences in the type of patient and
      the care needs between medical and surgical units may be a contributing factor to
      these findings. As members of the health team were among the leading source of
      interruptions, an interdisciplinary team-based approach to changing the
      organization and design of work should be explored. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse leaders should examine ways in which nurses' work can benefit
      from system improvements to reduce interruptions that lead to patient safety
      issues such as treatment delays and loss of concentration.

PMID- 21073576
TI  - Development and psychometric evaluation of the Core Nurse Resource Scale.
AB  - AIMS: To examine the factor structure, internal consistency reliability and
      concurrent-related validity of the Core Nurse Resource Scale. METHODS: A cross
      sectional survey study design was used to obtain a sample of 149 nurses and
      nursing staff [Registered Nurse (RNs), Licensed Practical Nurse (LPNs) and
      Certified Nursing Assistant (CNAs)] working in long-term care facilities.
      Exploratory factor analysis, Cronbach's alpha and bivariate correlations were
      used to evaluate validity and reliability. RESULTS: Exploratory factor analysis
      yielded a scale with 18 items on three factors, accounting for 52% of the
      variance in scores. Internal consistency reliability for the composite and Core
      Nurse Resource Scale factors ranged from 0.79 to 0.91. The Core Nurse Resource
      Scale composite scale and subscales correlated positively with a measure of work
      engagement (r=0.247-0.572). CONCLUSIONS: The initial psychometric evaluation of
      the Core Nurse Resource Scale demonstrates it is a sound measure. Further
      validity and reliability assessment will need to be explored and assessed among
      nurses and other nursing staff working in other practice settings. IMPLICATIONS
      FOR NURSING MANAGEMENT: The intent of the Core Nurse Resource Scale is to
      evaluate the presence of physical, psychological and social resources of the
      nursing work environment, to identify workplaces at risk for disengaged (low work
      engagement) nursing staff and to provide useful diagnostic information to
      healthcare administrators interested in interventions to improve the nursing work
      environment.

PMID- 21073577
TI  - Relationships among leadership practices, work environments, staff communication
      and outcomes in long-term care.
AB  - AIM: To examine the role that work relationships have on two long-term care
      outcomes: job satisfaction and turnover intention. BACKGROUND: It is easy to
      overlook the impact that human relations have in shaping work environments that
      are conducive to organizational effectiveness. Employee job satisfaction and
      retention are important organizational outcomes. METHODS: Six hundred and seventy
      five nursing and other staff from 26 long-term care facilities were surveyed
      about their work environments, work group relationships, observed leadership
      practices, organizational support, job satisfaction and turnover intention.
      RESULTS: Higher job satisfaction was associated with lower emotional exhaustion
      burnout, higher global empowerment, higher organizational support, higher
      psychological empowerment, stronger work group cohesion and higher personal
      accomplishment. Higher turnover intention was associated with lower job
      satisfaction, higher emotional exhaustion burnout, more outside job
      opportunities, weaker work group cohesion, lower personal accomplishment and
      higher depersonalization. CONCLUSIONS: No relationship was found between
      leadership practices and job satisfaction or turnover intention. Stronger work
      group relationships, stronger sense of personal accomplishment and lower
      emotional exhaustion have direct effects on increasing job satisfaction and
      lowering turnover intention. IMPLICATIONS: To retain long-term care staff,
      attention should be paid to fostering positive work group cohesion, supporting
      and acknowledging staff accomplishments and minimizing staff burnout.

PMID- 21073578
TI  - Impact and determinants of nurse turnover: a pan-Canadian study.
AB  - AIM: As part of a large study of nursing turnover in Canadian hospitals, the
      present study focuses on the impact and key determinants of nurse turnover and
      implications for management strategies in nursing units. BACKGROUND: Nursing
      turnover is an issue of ever-increasing priority as work-related stress and job
      dissatisfaction are influencing nurses' intention to leave their positions.
      METHODS: Data sources included the nurse survey, unit managers, medical records
      and human resources databases. A broad sample of hospitals was represented with
      nine different types of nursing units included. RESULTS: Nurses turnover is a
      major problem in Canadian hospitals with a mean turnover rate of 19.9%. Higher
      levels of role ambiguity and role conflict were associated with higher turnover
      rates. Increased role conflict and higher turnover rates were associated with
      deteriorated mental health. Higher turnover rates were associated with lower job
      satisfaction. Higher turnover rate and higher level of role ambiguity were
      associated with an increased likelihood of medical error. CONCLUSION: Managing
      turnover within nursing units is critical to high-quality patient care. A
      supportive practice setting in which role responsibilities are understood by all
      members of the caregiver team would promote nurse retention. IMPLICATIONS FOR
      NURSING MANAGEMENT: Stable nurse staffing and adequate managerial support are
      essential to promote job satisfaction and high-quality patient care.

PMID- 21073579
TI  - Long-term cytological and histological outcomes in women managed with loop
      excision treatment under local anaesthetic for high-grade cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: This study examines the impact of excision margin status after large
      loop excision of the transformation zone (LLETZ) under local anaesthetic for high
      grade cervical intraepithelial neoplasia (HG-CIN) on the cytological and
      histological outcomes up to 5 years after treatment. METHODS:   Prospective
      cytological and histological data were obtained by examination of the colposcopy
      database at Addenbrooke's Hospital, Cambridge, UK. All women aged between 19 and
      50 years who underwent treatment for HG-CIN by LLETZ under local anaesthetic were
      included in the study. Patients without follow-up data were excluded from the
      study. The excision margin status was correlated with the subsequent cytological
      and histological outcomes. RESULTS: A series of 967 women with CIN2 and CIN3
      underwent LLETZ excision under local anaesthetic. Overall, 42% of women had
      disease present at the excision margin following LLETZ. Women with CIN3 were more
      likely than those with CIN2 to have an involved excision margin (P<0.0001).
      Cytological recurrence was highest at 12 months (16%) and did not correlate with
      the CIN grade or excision margin status. Histological recurrence/persistence was
      also highest at 12 months follow-up (15%) and this correlated with grade of CIN
      and margin status (P<0.0001). CONCLUSIONS: Histological recurrence/persistence
      correlates with grade of CIN and excision margin status. Management of HG-CIN in
      an outpatient setting under local anaesthetic is safe, cost effective and yields
      a favourable long-term outcome.

PMID- 21073581
TI  - Postnatal disclosure of domestic violence: comparison with disclosure in the
      first trimester of pregnancy.
AB  - AIMS AND OBJECTIVES: This study explored the prevalence rates of domestic
      violence reported during the first trimester of pregnancy and in the postnatal
      period. BACKGROUND: Domestic violence is known to have a deleterious effect on
      the physical and psychological well-being of a woman, with an adverse effect on
      the unborn child. DESIGN: A validated anonymous and self-administered
      questionnaire (Abuse Assessment Screen) using five closed questions was used for
      data collection in all samples. All women were approached alone, and the
      questionnaire was completed in private. METHOD: Drawn from the same geographical
      area, this survey collected data from women accessing hospital clinics, in a
      large university teaching hospital in the UK. RESULTS: Comparing self-reporting
      rates of domestic violence in the first trimester of pregnancy to the postnatal
      period yielded statistically significant results (p < 0.01). Only 7.3% booking-in
      clinic and 8% postnatal women reported violence at some stage in their life,
      whilst higher rates in pregnancy counselling clinic (35.1%) and early pregnancy
      unit (26%) were reported. However, the reported rates of domestic violence in the
      year before the women were pregnant revealed a different trajectory. Lower rates
      of domestic violence were evident in three samples. CONCLUSIONS: The disparity in
      disclosure rates of domestic violence suggests that an emotional inhibitory
      response to disclosure may occur at specific periods of pregnancy and that the
      timing of asking about domestic violence may be critical to this disclosure. The
      pandemic nature of domestic violence reflects the need for practice in maternity
      care to reflect the changing needs of a woman during her gestational experience.
      RELEVANCE TO CLINICAL PRACTICE: The primary objective of health care providers
      should be to engage a pregnant woman in a meaningful relationship, gaining her
      trust to facilitate the disclosure of domestic violence. Hence, whatever the
      policies for the provision of maternity care, the changing needs of a pregnant
      woman must be met.

PMID- 21073580
TI  - Fixed versus variable dose of prothrombin complex concentrate for counteracting
      vitamin K antagonist therapy.
AB  - BACKGROUND: Although prothrombin complex concentrate (PCC) is often used to
      counteract vitamin K antagonist (VKA) therapy, evidence regarding the optimal
      dose for this indication is lacking. In Dutch hospitals, either a variable dose,
      based on body weight, target INR (international normalised ratio) and initial
      INR, or a fixed dose is used. AIM/OBJECTIVES: In this observational, pilot study,
      the efficacy and feasibility of the fixed dose strategy compared to the variable
      dosing regimen, is investigated. MATERIALS AND METHODS: Consecutive patients
      receiving PCC (Cofact(r), Sanquin, Amsterdam) for VKA reversal because of a major
      non-cranial bleed or an invasive procedure were enrolled in two cohorts. Data
      were collected prospectively in the fixed dose group, cohort 1, and
      retrospectively in the variable dose regimen, cohort 2. Study endpoints were
      proportion of patients reaching target INR and successful clinical outcome.
      RESULTS: Cohort 1 consisted of 35 and cohort 2 of 32 patients. Target INR was
      reached in 70% of patients in cohort 1 versus 81% in cohort 2 (P = 0.37).
      Successful clinical outcome was seen in 91% of patients in cohort 1 versus 94% in
      cohort 2 (P = 1.00). Median INR decreased from 4.7 to 1.8 with a median dosage of
      1040 IU factor IX (F IX) in cohort 1 and from 4.7 to 1.6 with a median dosage of
      1580 IU F IX in cohort 2. CONCLUSION: This study suggests that a fixed dose of
      1040 IU of F IX may be an effective way to rapidly counteract VKA therapy in our
      patient population and provides a basis for future research.

PMID- 21073582
TI  - Fluid manipulation among individuals with lower urinary tract symptoms: a mixed
      methods study.
AB  - AIMS AND OBJECTIVE: To determine, qualitatively and quantitatively, how
      individuals use fluid manipulation to self-manage the urinary symptoms of daytime
      frequency, urgency and urine leakage and the underlying rationale for this
      behaviour. BACKGROUND: Lower urinary tract symptoms are prevalent and burdensome,
      and little is known about how individuals with lower urinary tract symptoms
      manipulate their fluid intake. DESIGN: A mixed methods design included
      statistical analysis of data from a population-based survey of urologic symptoms
      and qualitative analysis of in-depth interviews. METHOD: Quantitative data came
      from 5503 participants of the baseline Boston Area Community Health Survey, a
      population-based, random sample epidemiologic survey of urologic symptoms.
      Qualitative data came from in-depth interviews with a random subsample from
      Boston Area Community Health of 152 black, white and Hispanic men and women with
      LUTS. RESULTS: Qualitative data showed that some respondents restricted fluid
      intake while others increased it, in both cases with the expectation of improved
      symptoms. Quantitative data showed that fluid intake was greater in men and women
      reporting frequency (p < 0.001). Women with frequency drank significantly more
      water (p < 0.001), while women with urgency drank significantly less water (p =
      0.047). CONCLUSIONS: This study found divergent expectations of the role of
      fluids in alleviating symptoms, leading some individuals to restrict and others
      to increase fluid intake. Individuals with lower urinary tract symptoms may need
      guidance in fluid management. RELEVANCE TO CLINICAL PRACTICE: Nurses should be
      aware that patients may self-manage lower urinary tract symptoms by restricting
      fluid intake, putting them at risk for dehydration, constipation and urinary
      tract infection, but also that they may be increasing their fluid intake, which
      could worsen symptoms. This study pinpoints a specific area of need among
      patients with lower urinary tract symptoms and provides a practical opportunity
      for nurses to assist their patients with behavioural and fluid management by
      emphasising the clinical guidelines.

PMID- 21073584
TI  - Genetic basis of infectivity evolution in a bacteriophage.
AB  - Antagonistic coevolution between hosts and parasites is probably ubiquitous.
      However, very little is known of the genetic changes associated with parasite
      infectivity evolution during adaptation to a coevolving host. We followed the
      phenotypic and genetic changes in a lytic virus population (bacteriophage; phage
      Phi2) that coevolved with its bacterial host, Pseudomonas fluorescens SBW25.
      First, we show the rapid evolution of numerous unique phage infectivity
      phenotypes, and that both phage host range and bacterial resistance to individual
      phage increased over coevolutionary time. Second, each of the distinct phage
      phenotypes in our study had a unique genotype, and molecular evolution did not
      act uniformly across the phage genome during coevolution. In particular, we
      detected numerous substitutions on the tail fibre gene, which is involved in the
      first step of the host-parasite interaction: host adsorption. None of the
      observed mutations could be directly linked with infection against a particular
      host, suggesting that the phenotypic effects of infectivity mutations are
      probably epistatic. However, phage genotypes with the broadest host ranges had
      the largest number of nonsynonymous amino acid changes on genes implicated in
      infectivity evolution. An understanding of the molecular genetics of phage
      infectivity has helped to explain the complex phenotypic coevolutionary dynamics
      in this system.

PMID- 21073585
TI  - Disease in the dark: molecular characterization of Polychromophilus murinus in
      temperate zone bats revealed a worldwide distribution of this malaria-like
      disease.
AB  - For a better understanding of the complex coevolutionary processes between hosts
      and parasites, accurate identification of the actors involved in the interaction
      is of fundamental importance. Blood parasites of the Order Haemosporidia,
      responsible for malaria, have become the focus of a broad range of studies in
      evolutionary biology. Interestingly, molecular-based studies on avian malaria
      have revealed much higher species diversity than previously inferred with
      morphology. Meanwhile, studies on bat haemosporidian have been largely neglected.
      In Europe, only one genus (Polychromophilus) and two species have been
      morphologically described. To evaluate the presence of potential cryptic species
      and parasite prevalence, we undertook a molecular characterization of
      Polychromophilus in temperate zone bats. We used a nested-PCR approach on the
      cytochrome b mitochondrial gene to detect the presence of parasites in 237 bats
      belonging to four different species and in the dipteran bat fly Nycteribia
      kolenatii, previously described as being the vector of Polychromophilus.
      Polychromophilus murinus was found in the four bat species and in the insect
      vector with prevalence ranging from 4% for Myotis myotis to 51% for M.
      daubentoni. By sequencing 682 bp, we then investigated the phylogenetic
      relationships of Polychromophilus to other published malarial lineages. Seven
      haplotypes were found, all very closely related, suggesting the presence of a
      single species in our samples. These haplotypes formed a well-defined clade
      together with Haemosporidia of tropical bats, revealing a worldwide distribution
      of this parasite mostly neglected by malarial studies since the 1980s.

PMID- 21073583
TI  - Mining the plant-herbivore interface with a leafmining Drosophila of Arabidopsis.
AB  - Experimental infections of Arabidopsis thaliana (Arabidopsis) with genomically
      characterized plant pathogens such as Pseudomonas syringae have facilitated the
      dissection of canonical eukaryotic defence pathways and parasite virulence
      factors. Plants are also attacked by herbivorous insects, and the development of
      an ecologically relevant genetic model herbivore that feeds on Arabidopsis will
      enable the parallel dissection of host defence and reciprocal resistance pathways
      such as those involved in xenobiotic metabolism. An ideal candidate is Scaptomyza
      flava, a drosophilid fly whose leafmining larvae are true herbivores that can be
      found in nature feeding on Arabidopsis and other crucifers. Here, we describe the
      life cycle of S. flava on Arabidopsis and use multiple approaches to characterize
      the response of Arabidopsis to S. flava attack. Oviposition choice tests and
      growth performance assays on different Arabidopsis ecotypes, defence-related
      mutants, and hormone and chitin-treated plants revealed significant differences
      in host preference and variation in larval performance across Arabidopsis
      accessions. The jasmonate and glucosinolate pathways in Arabidopsis are important
      in mediating quantitative resistance against S. flava, and priming with jasmonate
      or chitin resulted in increased resistance. Expression of xenobiotic
      detoxification genes was reduced in S. flava larvae reared on Arabidopsis
      jasmonate signalling mutants and increased in plants pretreated with chitin.
      These results and future research directions are discussed in the context of
      developing a genetic model system to analyse insect-plant interactions.

PMID- 21073587
TI  - Measures of immune function of wild mice, Mus musculus.
AB  - The immune function of wild animals has been rather little studied. Wild animals'
      immune function may differ from that of laboratory bred animals because of their
      different environments. This idea follows from the concept of resource
      partitioning in which animals distribute scarce resources to all aspects of life,
      including to costly immune responses. A logical extension of this idea is that
      there may be substantial interindividual variation in the immune function of wild
      animals. To begin to investigate this, we compared the immune function of a
      laboratory bred mouse strain (C57BL/6, a widely used mouse strain that makes
      potent immune responses) and wild caught Mus musculus. We found that by most
      measures of immune function, the wild caught mice had greater immune function.
      Specifically, wild mice had greater concentrations and more avid antigen-specific
      IgG responses, as well as higher concentrations of total IgG and IgE, compared
      with those laboratory bred mice. Moreover, flow cytometric analysis showed a
      comparatively greater overall level of activation of the cells of the immune
      system in wild mice. Lastly, we observed that immune function was substantially
      more variable among wild caught mice than among the laboratory bred mice. The
      next research challenge is to understand which aspects of an individual animal's
      life determine its immune function.

PMID- 21073586
TI  - Interspecific exchange of avian influenza virus genes in Alaska: the influence of
      trans-hemispheric migratory tendency and breeding ground sympatry.
AB  - The movement and transmission of avian influenza viral strains via wild migratory
      birds may vary by host species as a result of migratory tendency and sympatry
      with other infected individuals. To examine the roles of host migratory tendency
      and species sympatry on the movement of Eurasian low-pathogenic avian influenza
      (LPAI) genes into North America, we characterized migratory patterns and LPAI
      viral genomic variation in mallards (Anas platyrhynchos) of Alaska in comparison
      with LPAI diversity of northern pintails (Anas acuta). A 50-year band-recovery
      data set suggests that unlike northern pintails, mallards rarely make trans
      hemispheric migrations between Alaska and Eurasia. Concordantly, fewer (14.5%) of
      62 LPAI isolates from mallards contained Eurasian gene segments compared to those
      from 97 northern pintails (35%), a species with greater inter-continental
      migratory tendency. Aerial survey and banding data suggest that mallards and
      northern pintails are largely sympatric throughout Alaska during the breeding
      season, promoting opportunities for interspecific transmission. Comparisons of
      full-genome isolates confirmed near-complete genetic homology (>99.5%) of seven
      viruses between mallards and northern pintails. This study found viral segments
      of Eurasian lineage at a higher frequency in mallards than previous studies,
      suggesting transmission from other avian species migrating inter-hemispherically
      or the common occurrence of endemic Alaskan viruses containing segments of
      Eurasian origin. We conclude that mallards are unlikely to transfer Asian-origin
      viruses directly to North America via Alaska but that they are likely infected
      with Asian-origin viruses via interspecific transfer from species with regular
      migrations to the Eastern Hemisphere.

PMID- 21073588
TI  - The Strait of Gibraltar as a major biogeographic barrier in Mediterranean
      conifers: a comparative phylogeographic survey.
AB  - The Strait of Gibraltar (SG) is reputed for being both a bridge and a geographic
      barrier to biological exchanges between Europe and Africa. Major genetic breaks
      associated with this strait have been identified in various taxa, but it is
      unknown whether these disjunctions have been produced simultaneously or by
      independent biogeographic processes. Here, the genetic structure of five conifers
      distributed on both sides of the SG was investigated using mitochondrial (nad1
      b/c, nad5-1, nad5-4 and nad7-1) and chloroplast (Pt1254, Pt15169, Pt30204,
      Pt36480, Pt71936 and Pt87268) DNA markers. The distribution of genetic variation
      was partially congruent between types of markers within the same species. Across
      taxa, there was a significant overlapping between the SG and the genetic breaks
      detected, especially for the four Tertiary species surveyed (Abies pinsapo
      complex, Pinus nigra, Pinus pinaster and Taxus baccata). For most of these taxa,
      the divergence of populations across the SG could date back to long before the
      Pleistocene glaciations. However, their strongly different cpDNA G(ST) and R(ST)
      values point out that they have had dissimilar population histories, which might
      include contrasting amounts of pollen-driven gene flow since their initial
      establishment in the region. The fifth species, Pinus halepensis, was genetically
      depauperated and homogenous on both sides of the SG. A further analysis of
      nuclear DNA sequences with coalescent-based isolation with migration models
      suggests a Pleistocene divergence of P. halepensis populations across the SG,
      which is in sharp contrast with the pre-Pleistocene divergence dates obtained for
      P. pinaster. Altogether, these results indicate that the genetic breaks observed
      across this putative biogeographical barrier have been produced by independent
      evolutionary processes related to the biological history of each individual
      species instead of a common vicariant phenomenon.

PMID- 21073589
TI  - High genetic diversity in the remnant island population of hihi and the genetic
      consequences of re-introduction.
AB  - The maintenance of genetic diversity is thought to be fundamental for the
      conservation of threatened species. It is therefore important to understand how
      genetic diversity is affected by the re-introduction of threatened species. We
      use establishment history and genetic data from the remnant and re-introduced
      populations of a New Zealand endemic bird, the hihi Notiomystis cincta, to
      understand genetic diversity loss and quantify the genetic effects of re
      introduction. Our data do not support any recent bottleneck events in the remnant
      population. Furthermore, all genetic diversity measures indicate the remnant hihi
      population has retained high levels of genetic diversity relative to other New
      Zealand avifauna with similar histories of decline. Genetic diversity (N(A) ,
      alleles per locus, allelic richness, F(IS) and H(S) ) did not significantly
      decrease in new hihi populations founded through re-introduction when compared to
      their source populations, except in the Kapiti Island population (allelic
      richness and H(S) ) which had very slow post-re-introduction population growth.
      The N(e) /N(c) ratio in the remnant population was high, but decreased in first
      level re-introductions, which together with significant genetic differentiation
      between populations (F(ST) & Fisher's exact tests) suggest that extant
      populations are diverging as a result of founder effects and drift. Importantly,
      simulations of future allele loss predict that the number of alleles lost will be
      higher in populations with a slow population growth, fewer founding individuals
      and with nonrandom mating. Interestingly, this species has very high levels of
      extra-pair paternity which may reduce reproductive variance by allowing social
      and floater males to reproduce a life history trait that together with a large
      remnant population size may help maintain higher levels of genetic diversity than
      expected.

PMID- 21073590
TI  - Nonadditive changes to cytosine methylation as a consequence of hybridization and
      genome duplication in Senecio (Asteraceae).
AB  - The merger of two or more divergent genomes within an allopolyploid nucleus can
      facilitate speciation and adaptive evolution in flowering plants. Widespread
      changes to gene expression have been shown to result from interspecific
      hybridisation and polyploidy in a number of plant species, and attention has now
      shifted to determining the epigenetic processes that drive these changes. We
      present here an analysis of cytosine methylation patterns in triploid F(1)
      Senecio (ragwort) hybrids and their allohexaploid derivatives. We observe that,
      in common with similar studies in Arabidopsis, Spartina and Triticum, a small but
      significant proportion of loci display nonadditive methylation in the hybrids,
      largely resulting from interspecific hybridisation. Despite this, genome
      duplication results in a secondary effect on methylation, with reversion to
      additivity at some loci and novel methylation status at others. We also observe
      differences in methylation state between different allopolyploid generations,
      predominantly in cases of additive methylation with regard to which parental
      methylation state is dominant. These changes to methylation state in both F(1)
      triploids and their allohexaploid derivatives largely mirror the overall patterns
      of nonadditive gene expression observed in our previous microarray analyses and
      may play a causative role in generating those expression changes. These similar
      global changes to DNA methylation resulting from hybridisation and genome
      duplication may serve as a source of epigenetic variation in natural populations,
      facilitating adaptive evolution. Our observations that methylation state can also
      vary between different generations of polyploid hybrids suggests that newly
      formed allopolyploid species may display a high degree of epigenetic diversity
      upon which natural selection can act.

PMID- 21073592
TI  - Peak endocardial acceleration signals for atrial mechanical activation.

PMID- 21073591
TI  - Inferring the colonization of a mountain range--refugia vs. nunatak survival in
      high alpine ground beetles.
AB  - It has long been debated whether high alpine specialists survived ice ages in
      situ on small ice-free islands of habitat, so-called nunataks, or whether glacial
      survival was restricted to larger massifs de refuge at the periphery. We evaluate
      these alternative hypotheses in a local radiation of high alpine carabid beetles
      (genus Trechus) in the Orobian Alps, Northern Italy. While summits along the
      northern ridge of this mountain range were surrounded by the icesheet as nunataks
      during the last glacial maximum, southern areas remained unglaciated. We analyse
      a total of 1366 bp of mitochondrial (Cox1 and Cox2) data sampled from 150
      individuals from twelve populations and 530 bp of nuclear (PEPCK) sequence
      sampled for a subset of 30 individuals. Using Bayesian inference, we estimate
      ancestral location states in the gene trees, which in turn are used to infer the
      most likely order of recolonization under a model of sequential founder events
      from a massif de refuge from the mitochondrial data. We test for the paraphyly
      expected under this model and for reciprocal monophyly predicted by a contrasting
      model of prolonged persistence of nunatak populations. We find that (i) only
      three populations are incompatible with the paraphyly of the massif de refuge
      model, (ii) both mitochondrial and nuclear data support separate refugial origins
      for populations on the western and eastern ends of the northern ridge, and (iii)
      mitochondrial node ages suggest persistence on the northern ridge for part of the
      last ice age.

PMID- 21073593
TI  - The effects of adhesive type and thickness on stress distribution in molars
      restored with all-ceramic crowns.
AB  - PURPOSE: This study investigated the effects of luting cement type and thickness
      on the stress distribution within all-ceramic crowns using finite element
      analysis. MATERIALS AND METHODS: An all-ceramic crown restoration of the
      mandibular right first molar was prepared according to standard dental processes
      and scanned using micro-computed tomography. Eight 3D FE models were then
      developed that accounted for two adhesive systems, each with cement thickness of
      60 MUm, 90 MUm, 120 MUm, and 150 MUm. The models were subjected to four loading
      conditions, and stresses in the veneer and core layers were evaluated. RESULTS:
      The stress distribution and maximum stresses in the veneer, core, and cement are
      presented in corresponding loading conditions. The cement with higher elastic
      modulus resulted in lower tensile stresses in the veneer and core layers, and the
      shear strength of the cement was critical to the intactness of the all-ceramic
      crown. CONCLUSION: The cement thickness acts as a cushion between the crown and
      dentin substrate. Although there is an optimal thickness (approximately 90 MUm)
      that can reduce the stress level in ceramic crowns, cement thickness is not very
      important to stresses in the core or veneer in most cases when compared to the
      influence of loading conditions or cement moduli.

PMID- 21073594
TI  - Moving toward the goals of health reform.

PMID- 21073595
TI  - Family acceptance in adolescence and the health of LGBT young adults.
AB  - ISSUE: the role of family acceptance as a protective factor for lesbian, gay,
      bisexual, and transgender (LGBT) adolescents and young adults has not been
      established. METHODS: a quantitative measure with items derived from prior
      qualitative work retrospectively assessed family accepting behaviors in response
      to LGBT adolescents' sexual orientation and gender expression and their
      relationship to mental health, substance abuse, and sexual risk in young adults
      (N= 245). FINDINGS: family acceptance predicts greater self-esteem, social
      support, and general health status; it also protects against depression,
      substance abuse, and suicidal ideation and behaviors. CONCLUSIONS: family
      acceptance of LGBT adolescents is associated with positive young adult mental and
      physical health. Interventions that promote parental and caregiver acceptance of
      LGBT adolescents are needed to reduce health disparities.

PMID- 21073597
TI  - Exploring relationships among maternal BMI, family factors, and concern for
      child's weight.
AB  - PROBLEM: in an effort to better understand child obesity, this study examined the
      association between family living location, family function, mother's body mass
      index (BMI), and mothers' attitudes and behaviors concerning child feeding.
      Recent research on obesity has shown there is limited information on family
      influence and parental perceptions and attitudes. METHODS: a cross-sectional
      analysis was performed on data from 47 mothers of school-aged children. FINDINGS:
      urban African-American mothers had higher BMIs and were significantly more
      concerned about their child's weight status than rural white mothers.
      Additionally, maternal BMI was associated with the total number of individuals in
      the household. CONCLUSION: results suggest the importance in understanding the
      family and community and its influence on childhood obesity. Armed with knowledge
      about family factors and parents' beliefs and perceptions, nurses can develop
      interventions that can assist families and communities to focus on healthy
      children feeding and weight management.

PMID- 21073598
TI  - Developmental health of infants and children subsequent to foster care.
AB  - BACKGROUND: every day, the United States child welfare system is entrusted with
      the care of over 400,000 children through foster care. The majority of children
      entering this social setting are infants, the most developmentally vulnerable.
      METHODS: bronfenbrenner's human health ecology model and Bowlby's attachment
      theory are used to delineate the social setting of foster care and its impact on
      developmental health, and elucidates the relationship between childhood
      experiences and the overall continuum of health. Additionally, the notion of
      inherited genes and environmental influences or epigenetics toward gene
      expression will be explored. RESULTS: research points out that what happens in
      childhood matters; the consequences of not addressing childhood adversity and the
      associated risk factors of foster care increase a child's risk for poor
      developmental health and other major illnesses noted later in life such as
      cardiac disease, depression, and even premature death. Healthcare providers and
      others charged with caring for this vulnerable population who understand the
      social setting of foster care and its impact on developmental health may help
      identify and treat developmental problems earlier, thus potentially reducing long
      term effects of abuse and neglect. CONCLUSION: improvement plans that promote
      best practice for child welfare must include those that directly address the
      unique developmental needs of all infants and children in foster care itself.
      Such plans will ensure that foster care as an intervention to protect vulnerable
      children at risk does not create more harm by reducing the associated risks and
      maximizing benefits while in foster care, and ensures that those born genetically
      vulnerable and disproportionately susceptible to poor outcomes in adversity are
      also protected and provided opportunities that promote optimal developmental
      health.

PMID- 21073596
TI  - Correlates of substance use severity among homeless youth.
AB  - PROBLEM: this cross-sectional study identified a number of factors that were
      correlated with drug-use severity among homeless youth. METHODS: to examine a
      commonly used measure of substance-use severity, the TCU Drug Screen II, in a
      convenience sample of 156 homeless youth, ages 15-25 from a drop-in site in Santa
      Monica, California. FINDINGS: higher drug-use severity scores were independently
      related to low levels of perceived health and maladaptive coping strategies.
      CONCLUSIONS: the findings from this study are particularly relevant in that they
      support previous results showing that psychosocial variables are related to
      substance use behavior among young populations.

PMID- 21073599
TI  - Approaches for mental health well-being in children and adolescents.

PMID- 21073600
TI  - Are we preparing our nursing workforce to provide mental health promotion?

PMID- 21073601
TI  - Taxol directly induces endoplasmic reticulum-associated calcium changes that
      promote apoptosis in breast cancer cells.
AB  - Calcium, a key regulator of cell survival, is also important in regulating
      apoptosis. Although the chemotherapeutic agent Taxol employs apoptosis to induce
      cell death, the exact mechanism of how it induces apoptosis and the role of
      calcium in this process remains unclear. The main intracellular calcium
      storehouse, the endoplasmic reticulum, was identified as a new important gateway
      in apoptosis, possibly providing a target for Taxol. The goal of this study was
      to investigate whether calcium changes associated with the endoplasmic reticulum,
      were directly or indirectly generated by Taxol at clinically relevant doses, and
      related to Taxol-induced apoptosis in breast cancer cells. Time-lapsed imaging
      techniques followed by an endoplasmic reticulum-targeted construct, cameleon
      D1ER, were used to monitor cytosol--endoplasmic reticulum calcium dynamics in MDA
      MB-468 (Bcl-2 negative) and MCF 7 (Bcl-2 positive) breast carcinoma cells.
      Apoptosis levels were measured with Annexin V and Propidium Iodide (PI) using
      flow cytometry. In both cell lines, Taxol at 2.5MUM (~10(-6) M) was observed to
      induce significant internal calcium changes, first a rapid endoplasmic reticulum
      calcium release and a transient cytosolic calcium increase upon Taxol addition.
      After several hours of Taxol treatment, the endoplasmic reticulum calcium store
      was gradually depleted, and a sustained cytosolic calcium elevation was observed
      before significant induction of apoptosis. Inhibition of these calcium changes
      decreased Taxol-induced apoptosis levels. In contrast, 0.2MUM Taxol (~10(-7)M)
      induced only a slight cellular calcium change, not enough to regulate apoptosis.
      Our findings demonstrate that endoplasmic reticulum calcium stores provide a
      direct target for Taxol action and are important for induction of apoptosis,
      independent of Bcl-2 status. Furthermore, our results show for the first time,
      that the role of calcium in Taxol-induced endoplasmic reticulum-mediated
      apoptosis is dependent on Taxol dosage.

PMID- 21073602
TI  - Combining fractional resurfacing and Q-switched ruby laser for tattoo removal.

PMID- 21073603
TI  - Strategy for eliminating gastric cancer in Japan.
AB  - A study conducted by the Japan Gast Study Group showed that eradication of
      Helicobacter pylori reduced the risk of gastric cancer by about one-third.
      However, it did not completely prevent the onset of latent gastric cancer among
      those at high risk (i.e., with atrophic gastritis). To prevent deaths from
      gastric cancer, it is necessary to eradicate H. pylori infection. We propose a
      program of risk stratification based on the presence of H. pylori infection with
      or without atrophic gastritis followed by targeted interventions. Those at no
      risk for gastric cancer (no H. pylori, no atrophic gastritis) need no therapy or
      follow-up. Those at low risk (H. pylori infected, nonatrophic gastritis) need
      only H. pylori eradication therapy. The smaller groups at high or very high risk
      need eradication and cancer surveillance. We estimated the costs and the benefits
      of this strategy. Gastric cancer screening by simultaneous measurement of serum
      pepsinogen and H. pylori antibody combined with eradication of H. pylori in all
      individuals at risk would initially increase national healthcare expenditure, but
      this would be offset by markedly reducing the cost of treating gastric cancer.
      The proposed strategy should prevent about 150,000 deaths from gastric cancer
      during the 5 years after its adoption. If the loss caused by these deaths is also
      taken into account, the economic effect of this strategy becomes enormous. It
      would probably reduce the incidence of gastric cancer by more than 80-90% within
      10 years. The Japanese government should take the initiative to implement this
      strategy as soon as possible.

PMID- 21073604
TI  - Younger siblings play a major role in Helicobacter pylori transmission among
      children from a low-income community in the Northeast of Brazil.
AB  - BACKGROUND AND AIMS: To further evaluate intrafamilial transmission of H. pylori
      infection during childhood, we investigated the prevalence of H. pylori in family
      members from a poor H. pylori high-prevalence urban community in the Northeast of
      Brazil. METHODS: H. pylori infection was investigated in 570 members of 128
      households, by (13) C-urea breath test in children and by ELISA in mothers and
      other adult relatives. RESULTS: The overall prevalence of H. pylori infection
      (376/570) increased with age (p < .001) and ranged from 28.9%, in children aged 6
      months to 5 years, to 82% in adults over 40 years. An H. pylori positive mother
      and the number of infected siblings are independent risk factors for childhood H.
      pylori infection (OR = 2.2, 95% CI = 1.0-4.6 and OR = 4.3, 95% CI = 2.3-8.1,
      respectively) The number of siblings, number of younger siblings, and number of
      infected younger siblings were also associated with the infection in the
      univariate analysis. The number of infected younger siblings remained
      independently associated with the infection (p = .000), even after controlling
      for all the above cited variables, in addition to the H. pylori status of
      siblings and mothers, age, number of people per room, and number of children in
      the household. CONCLUSION: The transmission of H. pylori occurs from infected
      mothers to their offspring and among siblings, notably from younger siblings to
      the older ones.

PMID- 21073605
TI  - Sequential metronidazole-furazolidone or clarithromycin-furazolidone compared to
      clarithromycin-based quadruple regimens for the eradication of Helicobacter
      pylori in peptic ulcer disease: a double-blind randomized controlled trial.
AB  - BACKGROUND: Furazolidone is a much cheaper drug with a very low resistance
      against Helicobacter pylori compared to clarithromycin. We aim to evaluate safety
      and efficacy of a sequential furazolidone-based regimen versus clarithromycin
      based therapy in H. pylori eradication for ulcer disease. MATERIALS: Patients
      with proven peptic ulcer or duodenitis were randomized into three groups: OAB-M
      F; metronidazole (M) (500 mg bid) for the first 5 days, followed by furazolidone
      (F) (200 mg bid) for the second 5 days; OAC-P; clarithromycin (C) (500 mg bid)
      for 10 days; and OAB-C-F; clarithromycin (500 mg bid) for the first 5 days and
      furazolidone (200 mg bid) for the second 5 days. All groups received omeprazole
      (O) (20 mg bid) and amoxicillin (A) (1 g bid). Groups OAB-M-F and OAB-C-F were
      also given bismuth subcitrate (B) (240 mg bid), whereas a placebo (P) was given
      to group OAC-P. Adverse events were scored and recorded. Two months after
      treatment, a C(13) -urea breath test was performed. RESULTS: Three hundred and
      ten patients were enrolled and 92 (OAB-M-F), 95 (OAC-P), and 98 (OAB-C-F)
      completed the study. The intention-to-treat eradication rates were 78.5% (95% CI
      = 69-85), 81.1% (95% CI = 73-88), and 82% (95% CI = 74-89), and per-protocol
      eradication rates were 91.3% (95% CI = 83-96), 90.4% (95% CI = 82-95), and 88.7%
      (95% CI = 81-94), for group OAB-M-F, OAC-P, and OAB-C-F, respectively.
      Eradication rate differences did not reach statistical significance. The most
      common adverse event, bad taste, occurred in all groups, but more frequently in
      groups OAC-P (34%) and OAB-C-F (32%), than OAB-M-F (14%) (p < .05). Adverse
      symptoms score were 0.88 +/- 2.05 in group OAB-M-F, 1.15 +/- 1.40 in group OAC-P,
      and 1.87 +/- 1.62 in group OAB-C-F. CONCLUSION: Furazolidone can replace
      clarithromycin in H. pylori eradication regimens because of lack of development
      of resistance and very low cost.

PMID- 21073606
TI  - Antibiotic resistance of Helicobacter pylori in Mazandaran, North of Iran.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence of
      resistances in Helicobacter pylori against commonly used antibiotics including
      metronidazole, clarithromycin, amoxicillin, and tetracycline in Iranian patients.
      METHODS: H. pylori isolates were collected from gastric biopsies from patients
      referred for upper gastrointestinal endoscopy at Tooba Medical Center, Sari,
      Iran, from 2007 to 2010. None of them had been using antibiotics for at least 8
      months. H. pylori was identified based on morphological shape and positive
      biochemical tests for catalase, oxidase, and urease activity. Antibiotic
      resistance for metronidazole, clarithromycin, amoxicillin, and tetracycline was
      investigated by using epsilometer test. Resistance was defined by minimal
      inhibitory concentration (MIC) > 0.5 mg/L for amoxicillin (AMX), >4 mg/L for
      tetracycline (TET), >8 mg/L for metronidazole (MTZ), and >1 mg/L for
      clarithromycin (CLR). RESULTS: Strains were collected from 132 patients, mean age
      45.8 years, 52 (39%) were women. Patients had diverse diagnoses: gastritis 42
      (31.8%), duodenal ulcer 45 (34%), gastric cancer 15 (11.3%), or gastric ulcer 30
      (22.7%). The prevalences of resistance of H. pylori strains isolated from the
      patients were 73.4% for metronidazole, 30% for clarithromycin, 6.8% for
      amoxicillin, and 9% for tetracycline. Twenty-eight (21.2%) were double resistant
      to MTZ-CLR, 16 (12.1%) showed triple resistance to MTZ-CLR-AMX, and 8 (6%) were
      resistant to all four tested antibiotics (MTZ-CLR-AMX-TET). No associations were
      detected between multiple resistant strains and clinical manifestations (p >
      .05). CONCLUSIONS: The prevalence of H. pylori antibiotic resistance to
      metronidazole and clarithromycin was high in Iran consistent with the reported
      low success rates for H. pylori treatment in this country.

PMID- 21073607
TI  - Long-term statin therapy affects the severity of chronic gastritis.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is a major cause of chronic
      gastritis. Statins have several pleotropic effects and their mechanisms of action
      could be related to anti-inflammatory, antioxidants, and immunomodulatory
      effects. AIM: To determine whether statin therapy affects the severity of chronic
      gastritis. MATERIALS AND METHODS: In a retrospective study, we evaluated 516
      patients who underwent upper endoscopy. One-hundred and ninety-eight patients had
      chronic gastritis, The 198 patients with chronic gastritis were divided into two
      groups: group 1 comprised patients with a history of statin therapy and group 2
      comprised patients with no history of statin therapy. Both groups were compared
      for age, gender, body mass index (BMI), underlying diseases, drug therapy,
      alcohol consumption, smoking and the serum levels of C-reactive protein (CRP).
      The presence of H. pylori was determined by gastric biopsy and rapid urease test.
      The grade and severity of gastritis were assessed using the updated Sydney
      classification system in two gastric biopsy specimens that were taken from each
      participant in each group. RESULTS: Of the 198 patients with chronic gastritis,
      49% of the patients had mild gastritis and 51% had moderate to severe gastritis.
      From the results of a multiple logistic regression analysis after adjusting for
      confounding variables that included age, gender, and BMI, we found that elevated
      serum CRP levels (odds ratio (OR) 2.33; 95% confidence interval (CI) = 0.8-2.6, p
      = .02), H. pylori (OR 1.99; CI 0.14-2.4, p = .04), and the use of statin (OR
      1.64; CI = 0.71-1.77, p = .05) independently predict the severity of chronic
      gastritis. CONCLUSION: Long-standing statin therapy may reduce the severity of
      chronic gastritis. Mild increased CRP levels in absence of obvious source can
      predict the severity of chronic gastritis. Further researches are needed to
      assess the effect of statin in chronic gastritis.

PMID- 21073608
TI  - Risk factors associated with gastric cancer in patients with a duodenal ulcer.
AB  - BACKGROUND: Although gastric cancer (GC) and duodenal ulcer (DU) are both
      strongly associated with Helicobacter pylori infection, a DU is negatively
      associated with the risk of GC. The aim of the study is to evaluate histologic
      risk factors for GC among patients with a DU. MATERIALS AND METHODS: A total of
      541 consecutive patients with GC were prospectively evaluated for the presence of
      a DU. Control patients with only a DU (n = 89) were recruited from health
      screening population. Histologic grading was assessed using the updated Sydney
      system for six gastric biopsies from three regions. GC risk among patients with a
      DU was evaluated using logistic regression analysis. RESULTS: Among patients with
      GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus
      predominant/pangastritis were more frequently found in concomitant GC patients
      with a DU (90%) than in patients with a DU alone (62%) (p = .001). In patients
      with a DU, moderate-severe chronic inflammation at the lesser and greater
      curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46-9.36,
      and OR, 7.72; 95% CI, 3.18-18.7, respectively). Additionally, moderate-severe
      intestinal metaplasia (IM) at the antrum and corpus lesser curvature was
      associated with GC risk (OR, 7.52; 95% CI, 3.06-18.5, and OR, 9.25, 95% CI, 2.39
      35.8, respectively). CONCLUSIONS: A DU is not rare in patients with GC in a high
      risk region of GC. Patients with a DU with chronic corpus gastritis and IM have
      an increased risk of GC, thus those patients should be followed up for GC
      development.

PMID- 21073609
TI  - Association between common genetic variants in pre-microRNAs and gastric cancer
      risk in Japanese population.
AB  - BACKGROUND: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA)
      have been shown to be associated with susceptibility to several human cancers. We
      evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444)
      in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of gastric cancer
      (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori
      induced gastritis in Japanese population. METHODS: The rs11614913 (C>T),
      rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non
      cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non-ulcer
      subjects. The degree of histologic gastritis was classified according to the
      updated Sydney System, and the serum pepsinogen levels were measured in selected
      579 and 204 cases. RESULTS: The rs2910164 CC genotype held a significantly higher
      risk of GC when compared to non-cancer subjects (adjusted odds ratio (OR) = 1.30,
      95% confidence interval (CI) = 1.02-1.66, p =.03). Similarly, the rs2910164 C
      carrier was associated with higher risk of GC when compared to both non-cancer
      and non-ulcer subjects (OR = 1.39, 95%CI = 1.00-1.93, p =.05, adjusted OR = 1.57,
      95%CI = 1.09-2.27, p =.016, respectively). The rs2910164 CC genotype was
      associated with non-cardia and upper third, diffuse type and advanced stage GC.
      The rs11614913 TT genotype was associated with higher degree of mononuclear cell
      infiltration (score 0-1 vs 2~, adjusted OR = 1.62, 95%CI = 1.05-2.49, p =.03).
      CONCLUSIONS: The rs2910164 (G>C) SNP in the miR-146a is associated with
      susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR-196a2 is
      associated with the degree of H. pylori-induced mononuclear cell infiltration.

PMID- 21073610
TI  - Seroprevalence rates of Helicobacter pylori and viral hepatitis A among
      adolescents in three regions of the Kingdom of Saudi Arabia: is there any
      correlation?
AB  - BACKGROUND: The seroprevalence rate of Helicobacter pylori in the Kingdom of
      Saudi Arabia (KSA) was reported to be in the range of 50-80% among mostly
      symptomatic patients in non-community-based studies. However, the seroprevalence
      of viral hepatitis A (HAV) underwent a marked decline in the last two decades
      from over 50% in 1989 to 25% in 1997 among Saudi children under the age of 12
      years. The aim of this paper was to study seroprevalence rates of H. pylori and
      HAV among the adolescent population in three regions of KSA and to determine
      whether there was any correlation between them. MATERIALS AND METHODS: We
      randomly selected 1200 16-18-year-old students from three regions around KSA.
      Demographic data, including socioeconomic status (SES), were recorded, and each
      student was tested for the presence of H. pylori-IgG antibodies and anti-HAV-IgG.
      RESULTS: The results indicate a high H. pylori infection rate (47%) among this
      age group. Boys had a higher prevalence than girls (p = .03), and the Al-Qaseem
      region had the highest prevalence (51%, p = .002). SES did not contribute to the
      high prevalence rates (p = .83). A cross-tabulation of data showed that 88 (8%)
      of the teenagers were seropositive and that 512 (44%) were negative for both H.
      pylori and HAV antibodies (chi(2) = 0.03, OR = 0.97, CI = 0.70-1.34). The
      agreement between H. pylori and HAV seropositivity was lower than would be
      predicted by chance (kappa = -0.03). The variables that were independently
      associated with seropositivity to H. pylori were being female (OR = 0.75, 95% CI
      = 0.60-0.95) and living in the Madinah region (OR = 0.72, 95% CI = 0.55-0.94).
      CONCLUSION: The prevalence of H. pylori in this group of adolescents was high.
      However, there was no correlation between H. pylori and HAV infection rates.
      Hence, factors contributing to the transmission source and route seem to be
      different.

PMID- 21073611
TI  - Induction of high endothelial venule-like vessels expressing GlcNAc6ST-1-mediated
      L-selectin ligand carbohydrate and mucosal addressin cell adhesion molecule 1
      (MAdCAM-1) in a mouse model of "Candidatus Helicobacter heilmannii"-induced
      gastritis and gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
AB  - BACKGROUND: "Candidatus Helicobacter heilmannii" induce chronic gastritis, which
      eventually leads to gastric B-cell type mucosa-associated lymphoid tissue (MALT)
      lymphoma. This study was performed using an animal model of infection with
      "Candidatus Helicobacter heilmannii" to elucidate how this chronic inflammation
      is induced or maintained. MATERIALS AND METHODS: BALB/c mice were infected with
      the "Candidatus Helicobacter heilmannii" isolate SH4. The animals were examined
      at 8, 26, 54, and 83 weeks after the infection. The stomach of the animals was
      resected and immunostained for peripheral lymph node addressin (PNAd) and mucosal
      addressin cell adhesion molecule 1 (MAdCAM-1), "Candidatus Helicobacter
      heilmannii," and CD45R/B220. An in vitro binding assay with L- and E-selectin.IgM
      chimeric proteins was performed. Real-time polymerase chain reaction was used to
      evaluate transcripts of N-acetylglucosamine-6-O-sulfotransferases (GlcNAc6STs),
      which direct the expression of the PNAd and MAdCAM-1. RESULTS: Chronic gastritis
      developed in the infected animals, and its severity increased with the duration
      of the infection. B-cell type MALT lymphoma developed in some animals at 54 and
      83 weeks after infection. PNAd- and MAdCAM-1-expressing high endothelial venule
      (HEV)-like vessels were induced in infected animals which developed chronic
      gastritis and MALT lymphoma. The number of HEV-like vessels increased as chronic
      inflammation progressed. The induced HEV-like vessels were bound by L- and E
      selectin.IgM chimeric protein. mRNA expressions of GlcNAc6ST-1 and MAdCAM-1
      increased in the infected animals. CONCLUSIONS: HEV-like vessels expressing
      GlcNAc6ST-1-mediated L-selectin ligand carbohydrate and MAdCAM-1 may play a
      crucial role in the pathogenesis of "Candidatus Helicobacter heilmannii"-induced
      chronic gastritis and MALT lymphoma.

PMID- 21073612
TI  - Detection of Helicobacteraceae in intestinal biopsies of children with Crohn's
      disease.
AB  - BACKGROUND: Given that members of Helicobacteraceae family colonize the
      intestinal mucus layer, it has been hypothesized that they may play a role in
      Crohn's disease. This study investigated the presence of Helicobacteraceae DNA in
      biopsies collected from children with Crohn's disease and controls. MATERIALS AND
      METHODS: The presence of Helicobacteraceae DNA was investigated in intestinal
      biopsies collected from 179 children undergoing colonoscopy (Crohn's disease n =
      77, controls n = 102) using a Helicobacteraceae-specific PCR. RESULTS: Members of
      the Helicobacteraceae were detected in 32/77 children with Crohn's disease
      (41.5%) and 23/102 controls (22.5%). Statistical analysis showed the prevalence
      of Helicobacteraceae detected in patients to be significantly higher than that in
      controls (p = .0062). Analysis of non-pylori Helicobacteraceae showed that their
      prevalence was also significantly higher in patients than in controls (p = .04).
      Helicobacter pylori was detected in 14.0% of the biopsies across all groups.
      Given that all children tested were negative for gastric H. pylori, this was a
      surprising finding. Phylogenetic analysis of H. pylori sequences detected in the
      biopsies showed that the H. pylori strains identified in the patients did not
      group with gastric H. pylori included in the analysis, but rather with other H.
      pylori strains detected in the intestine, gall bladder, and liver. CONCLUSIONS:
      The higher prevalence of Helicobacteraceae DNA in Crohn's disease patients would
      suggest that members of this family may be involved in this disease. In addition,
      phylogenetic analysis of H. pylori strains showed that extragastric sequences
      clustered together, indicating that different H. pylori strains may adapt to
      colonize extragastric niches.

PMID- 21073613
TI  - Identification of a correlation between Helicobacter pylori infection and Graves'
      disease.
AB  - BACKGROUND: Viral and bacterial antigens have been suspected to be able to mimic
      the antigenic profile of the thyroid cell membrane and to play an important role
      in the onset of the autoimmune diseases, such as Graves' disease and Hashimoto
      thyroiditis. The Helicobacter pylori infection is worldwide diffused and is
      present in the developed countries up to 50% of the population. The presence of
      the cytotoxin-associated gene A antigens identifies the most virulent strains of
      the bacterium. Previous studies have demonstrated the possible correlation
      between the Helicobacter pylori and Hashimoto's thyroiditis but these results are
      controversial. AIMS: We studied the prevalence rate of this bacterium in the
      Graves' disease and two selected subgroups such as the hyperthyroid patients, at
      the first time of diagnosis, and the euthyroid methimazole-treated patients.
      MATERIALS AND METHODS: We analyzed Helicobacter pylori in fresh stool samples
      with an enzyme immunoassay method and the presence of cytotoxin-associated gene A
      antigens with a serological test. RESULTS: Our results show that a significative
      increased rate of prevalence is present in Graves' patients, when the disease is
      ongoing, with an overall prevalence of the strains expressing the cytotoxin
      associated gene A antigens compared to the control group. CONCLUSIONS: The
      association between the Helicobacter pylori and Graves' disease suggests a
      possible role of this bacterium in the onset and/or the maintenance of the
      disease.

PMID- 21073614
TI  - Outcomes from chemoradiotherapy for patients with esophageal cancer.
AB  - Chemoradiotherapy is a widely used alternative treatment to surgical resection in
      certain patient groups with early esophageal cancer. The aim of this study was to
      retrospectively assess toxicity and outcome of patients treated with definitive
      chemoradiotherapy for early esophageal cancer at one institution. A retrospective
      analysis of all patients treated with chemoradiotherapy between February 2000 and
      December 2008 at a single tertiary center was performed with documentation of
      treatment given, toxicities recorded, and follow-up and outcome data. Sixty-two
      patients received chemoradiotherapy for esophageal cancer. There were 20 males
      and 42 female patients with an average age of 68 years. Histology revealed
      adenocarcinoma in 28 patients and squamous cell carcinoma in 34 patients. All
      patients were staged with a computerized tomography scan, endoscopic ultrasound
      and positron emission tomography scan. Selection criteria for chemoradiotherapy
      were unfit for surgery, upper esophageal squamous carcinoma, unresectable primary
      tumor, or patient choice. The majority of the patients received a combination of
      cisplatin and 5-fluorouracil chemotherapy with 55 Gy in 25 fractions of
      radiotherapy. Grade 3 toxicities were recorded in 11% of the patients. Eleven
      patients suffered from local recurrence and a stent was required in nine
      patients. Radiation strictures occurred in 10 patients requiring dilation in
      four. Five patients required a radiologically inserted feeding gastrostomy. The
      median overall survival was 21 months. Patients with adenocarcinomas and those
      with squamous cell carcinoma had a similar median survival. Overall survival was
      70% at 1 year, 48% at 2 years, and 26% at 3 years. This case series of patients
      treated with chemoradiation for localized esophageal cancer suggest a generally
      well-tolerated treatment with survival rates after chemoradiotherapy comparable
      with those seen with surgery.

PMID- 21073615
TI  - Prognostic value of hypoxia inducible factor 1alpha in esophageal squamous cell
      carcinoma.
AB  - Hypoxia inducible factor 1alpha (HIF 1alpha) plays a major role in the pleitropic
      response observed secondary to hypoxic conditions in tumors. Its expression in
      the tumor cells has been correlated to tumor aggressiveness and prognosis in
      squamous cell carcinoma (SCC) of the esophagus in Far Eastern population, but
      limited information is available on the prognostic role of HIF 1alpha in SCC of
      esophagus in European population. This information may help in choosing
      appropriate therapeutic strategies and possibly developing a monoclonal antibody
      with therapeutic potential targeting the HIF 1alpha. Tumor samples from 36
      patients diagnosed with SCC of the esophagus were collected. Prepared tissue
      sections were stained with validated and specific monoclonal antibodies for HIF
      1alpha and the expression was correlated with the disease pattern and survival.
      Out of 36 patients, 17 patients showed low and 19 high expression of HIF 1alpha.
      There was no difference in the disease-free and overall survival between these
      two groups (P > 0.05, log rank test). Regression analysis showed that HIF 1alpha
      was not an independent prognostic factor for survival (P > 0.05). HIF 1alpha did
      not show prognostic value in SCC of the esophagus in our study on European
      population, in agreement with previous studies. Novel strategies on the
      therapeutic manipulation of HIF 1alpha in cancer are to be explored further and
      may have a role to play in improving treatment outcome.

PMID- 21073616
TI  - Trends and perioperative outcomes of inpatient antireflux surgery in the United
      States, 1993-2006.
AB  - Antireflux surgery is an effective treatment for gastroesophageal reflux disease,
      but postoperation complications and durability may be problematic. The objective
      of the study was to determine whether inpatient antireflux surgery continued to
      decline in the United States due to concerns about its long-term effectiveness
      and the popularity of gastric bypass surgery and to assess recent changes in its
      perioperative outcomes. Using the Nationwide Inpatient Sample, we identified
      adult patients undergoing inpatient antireflux surgery during 1993-2006 and
      compared the trends of inpatient antireflux surgery with inpatient gastric bypass
      surgery. Perioperative complications included laceration, splenectomy,
      transfusion, esophageal dilation, total parenteral nutrition, and infection.
      Inpatient antireflux surgery increased from 9173 in 1993 to 32 980 in 2000
      (+260%) but then decreased to 19 668 in 2006 (-40%). Compared with 2000, patients
      undergoing inpatient antireflux surgery in 2006 were older (49.9 +/- 32.4 vs.
      54.6 +/- 33.6 years) and had a longer length of stay (3.1 +/- 10.0 vs. 3.7 +/-
      13.4 days), more complications (4.7% vs. 6.1%), and higher mortality (0.26% vs.
      0.54%) (all P < 0.05). Compared with inpatient gastric bypass surgery, length of
      stay was longer and mortality was higher for inpatient antireflux surgery in
      2006, but neither was significant controlling for age. In 2006, perioperative
      outcomes of inpatient antireflux surgery were better in high-volume hospitals
      (all P < 0.01). Inpatient antireflux surgery continued to decline in the United
      States from 2000 to 2006, concomitant with a dramatic increase in inpatient
      gastric bypass surgery. Older patient age and worsening perioperative outcomes
      for inpatient antireflux surgery suggest increased medical complexity and
      possibly a larger share of reoperations over time. Designating centers of
      excellence for antireflux surgery based on local expertise may improve outcomes.

PMID- 21073617
TI  - Achalasia familiar: report of a family with an autosomal dominant pattern of
      inherence.
AB  - Esophageal achalasia is a well-known pathology with an autosomal recessive
      pattern of inherence described in the familiar cases. Its principal symptom is
      dysphagia, secondary to the poor relaxation of the lower esophageal sphincter.
      Chagas disease is one of the many causes involved in the development of this
      disease, being of great importance in our country because of the high prevalence
      of the vector. Various syndromes include achalasia in their symptomatology, such
      as the triple A syndrome or Allgrove syndrome (Addisonianism, achalasia, and
      alacrimia). We reported a family with a classical autosomal pattern of inherence
      with six affected members, four men and two women, with achalasia diagnosis as
      well as esophagus cancer in two of them, secondary to the disease, and no other
      findings.

PMID- 21073618
TI  - Clinical study on lymph node metastatic recurrence in patients with N0 esophageal
      squamous cell cancer.
AB  - Esophageal squamous cell cancer (ESCC) is one of the most common malignancies
      treated by thoracic surgeons. It is aggressive and generally associated with a
      poor prognosis. One of the most important prognostic factors is the presence of
      the lymph node metastasis (LNM). The purpose of the present study was to
      investigate the risk factor with lymph node metastatic recurrence in patients
      with N0 esophageal squamous cancer after Ivor Lewis esophagectomy based on the
      detection of mucin1 (MUC1) mRNA. The subjects were 82 patients with pN0 ESCC who
      underwent Ivor Lewis esophagectomy with two-field lymph node dissection from
      January 2001 to January 2005. All lymph nodes (501 stations) obtained from these
      patients were reevaluated by reverse transcriptase-polymerase chain reaction (RT
      PCR) to detect MUC1mRNA. The diagnosis of lymph node micrometastasis (LNMM) was
      based on the detection of MUC1 mRNA. The Kaplan-Meier method was used to
      calculate the survival rate and lymph nodal metastatic rate. Log-rank test was
      performed to compare the recurrence rate, and Cox regression multivariate
      analysis was performed to determine independent prognostic factors. The overall 3
      year survival rates of 82 patients were 78.0%, and the first recurrence
      exhibiting lymph nodal metastasis was recognized in 37 patients (45.1%) in the
      first 3 years after operation. Lymph node metastatic rate in patients in the
      first 3 years after operation was significantly associated with the T status (P <
      0.05). MUC1 mRNA was identified in at least one lymph node station from 23
      (28.1%) patients. Also, lymph node metastatic rate of the patients with LNMM was
      significantly higher than that of the patients without LNMM (P < 0.01).The
      results of multivariate analysis confirmed that LNMM and T status in patients
      with N0 ESCC were independent risk factors for 3-year lymph node metastatic
      recurrence after Ivor Lewis esophagectomy. Adjunctive therapy might be beneficial
      in controlling the locoregional recurrence and elevated healing rates for certain
      patients.

PMID- 21073619
TI  - Prevalence of respiratory symptoms in patients with achalasia.
AB  - Achalasia is a primary esophageal motor disorder that results in poor clearance
      of the esophagus. Although an esophagus filled with debris and undigested food
      should put these patients at risk for aspiration, the frequency with which the
      latter occurs has never been documented. In this study, we sought to determine
      the incidence of respiratory symptoms and complaints in patients with achalasia.
      A comprehensive symptom questionnaire was administered to 110 patients with
      achalasia presenting to the Swallowing Center at the University of Washington
      between 1994 and 2008 as part of their preoperative work-up. Questionnaires were
      analyzed for the frequency of respiratory complaints in addition to the more
      typical symptoms of dysphagia, regurgitation, and chest pain. Twenty-two
      achalasia patients with respiratory symptoms who had also undergone Heller
      myotomy and completed a post-op follow-up questionnaire were analyzed as a
      subset. Ninety-five patients (86%) complained of at least daily dysphagia. Fifty
      one patients (40%) reported the occurrence of at least one respiratory symptom
      daily, including cough in 41 patients (37%), aspiration (the sensation of
      inhaling regurgitated esophagogastric material) in 34 patients (31%), hoarseness
      in 23 patients (21%), wheezing in 17 patients (15%), shortness of breath in 11
      patients (10%), and sore throat in 13 patients (12%). Neither age nor gender
      differed between those with and those without respiratory symptoms. In the subset
      of patients with respiratory symptoms who had undergone Heller myotomy,
      respiratory symptoms improved in the majority after the procedure. Patients with
      achalasia experience respiratory symptoms with much greater frequency than the
      approximately 10% that was previously believed. Awareness of this association may
      be important in the workup and ultimate treatment of patients with this uncommon
      esophageal disorder.

PMID- 21073621
TI  - Solitary esophageal leiomyoma with eosinophilic infiltrate: case report and
      review of the literature.
AB  - Leiomyomas are common benign tumors of the esophagus representing 10% of all
      mesenchymal tumors of the gastrointestinal tract. Prominent numbers of
      eosinophils involving a leiomyoma have only rarely been described. They have
      never been described involving a solitary leiomyoma of the esophagus. We present
      an unusual case of a solitary esophageal leiomyoma with a prominent number of
      eosinophils and mast cells, review the previous literature regarding this topic
      and discuss possible causes of the eosinophil infiltrate.

PMID- 21073620
TI  - ERK1/2 signaling pathway in mast cell activation-induced sensitization of
      esophageal nodose C-fiber neurons.
AB  - Sensitization of esophageal nociceptive afferents by inflammatory mediators plays
      an important role in esophageal inflammatory nociception. Our previous studies
      demonstrated that esophageal mast cell activation increases the excitability of
      esophageal nodose C-fibers. But the intracellular mechanism of this sensitization
      process is still less clear. We hypothesize that extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) signaling pathway plays an important role in mast cell
      activation-induced sensitization of esophageal nodose C-fiber neurons. Mast cell
      activation and in vivo esophageal distension-induced phosphorylations of ERK1/2
      were studied by immuno-staining and Western blot in esophageal nodose neurons.
      Extracellular recordings were performed from nodose neurons using ex vivo
      esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve
      excitabilities were compared by action potentials evoked by esophageal
      distensions before and after mast cell activations with/without pretreatment of
      mitogen-activated protein kinases (MAPK)/ERK kinase inhibitor U0126. The
      expressions of phospho-ERK1/2 (p-ERK1/2) in the same nodose ganglia were then
      studied by Western blot. Mast cell activation enhances in vivo esophageal
      distension-induced phosphorylation of ERK1/2 in nodose neurons. This can be
      prevented by pretreatment with mast cell stabilizer cromolyn. In ex vivo
      esophageal-vagal preparations, both mast cell activation and proteinase-activated
      receptor 2 (PAR2)-activating peptide perfusion increases esophageal distension
      induced mechano-excitability of esophageal nodose C-fibers and phosphorylation of
      ERK1/2 in nodose neurons. Pretreatment with MAPK/ERK kinase inhibitor U0126
      prevents these potentiation effects. Collectively, our data demonstrated that
      mast cell activation enhances esophageal distension-induced mechano-excitability
      and phosphorylation of ERK1/2 in esophageal nodose C-fiber neurons. This reveals
      a new intracellular pathway of esophageal peripheral sensitization and
      inflammatory nociception.

PMID- 21073622
TI  - The role of robotic assisted laparoscopy for oesophagogastric oncological
      resection; an appraisal of the literature.
AB  - The introduction of surgical robotics to the field of surgical oncology brings
      with it an expectation not only of improved vision, instrumentation, and
      precision but also as a result, a potential for improved oncological outcomes.
      The current interest in the field of oesophagogastric oncology is explored in
      this review together with the benefits, real and potential, that robotic
      assistance offers surgical cancer resection as well as some of the limiting
      factors which may be hampering its uptake into current surgical practice. A
      systematic review of all the published literature up until April 2010 was
      examined across the field of esophageal and gastric cancer resection. A
      quantitative assessment of the oncological, operative, and functional outcomes
      was determined from each procedure. The level of evidence behind the results was
      determined using the Oxford Centre for Evidence-based Medicine Levels of
      Evidence; Therapy and Prevention. Three hundred and five cases from 19
      independent studies were included for review. Nine studies explored the outcomes
      from robotic-assisted esophagectomy and eight, the robotic-assisted gastrectomy.
      Two articles included small case series of both procedures. The level of evidence
      was predominantly based on case series or expert opinion (Level 4 or 5) with only
      three unmatched or poorly matched comparative trials (Level 4) with no randomized
      trials evident. Improved operative outcomes and hospital stays were demonstrated
      with a reduction of 2 days when the robotic-assisted gastrectomy technique was
      employed compared with the open. No improvement in oncological outcomes could be
      identified with the use of the robot for either oesophageal or gastric cancer
      resection; however, in terms of short-term oncological outcomes, these were at
      least equivalent to the open approach for oesophageal cancer and early stage
      gastric cancer. Robotic-assisted laparoscopic surgery is a feasible technique to
      use to perform a safe and oncologically sound resection for oesophageal and early
      gastric cancer. Operative benefits appear to be encouragingly similar to the
      laparoscopic approach with some demonstration of improvement over the open
      technique despite a prolonged operative time. However, the level of evidence is
      suboptimal and more randomized controlled trials and long-term survival studies
      within a framework of measured and comparable outcomes is required.

PMID- 21073623
TI  - Phase I study of concurrent selective lymph node late course accelerated hyper
      fractionated radiotherapy and pemetrexed, cisplatin for locally advanced
      esophageal squamous cell carcinoma.
AB  - The optimized concurrent chemoradiotherapy has not been established for patients
      with advanced esophageal squamous cell carcinoma (SCC). The aim of the present
      study was to evaluate the safety and efficacy of concurrent chemotherapy and
      selective lymph node (SLN) late course accelerated hyperfractionated (LCAF)
      intensity modulated radiotherapy (IMRT) for the patients with thoracic SCC.
      Twelve patients with T3-4N0-1M0-1a thoracic esophageal SCC were included. The
      total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent
      chemotherapy protocol was as following: cisplatin 10 mg/m(2) on days 1-5 and 22
      26, pemetrexed in escalating doses, from the base level of 500 mg/m(2) once every
      21 days. The primary objectives were to determine the maximum tolerated dose
      (MTD), recommended dose (RD), and dose limiting toxicities (DLTs). Secondary end
      point included determination of preliminary radiographic response rates. As a
      result, three patients were enrolled in dose level 1 with pemetrexed 500 mg/m(2)
      and nine patients in dose level 0 with 400 mg/m(2) , respectively. At dose level
      1, DLTs occurred in two of three patients. However, only two of nine patients in
      Level 0 developed DLTs. The complete response and partial response were observed
      in eight and four patients, respectively. Furthermore, no patient experienced
      cancer progression with a median follow-up of 9 months. In conclusion, the
      concurrent SLN LCAF IMRT and chemotherapy is feasible. The MTD of pemetrexed in
      this regimen was 500 mg/m(2) and RD was 400 mg/m(2) . Although toxicities were
      common, the protocol was safe, well tolerated, and achieved an encouraging
      outcome.

PMID- 21073624
TI  - Small cell carcinoma of the esophagus: a multicentre Rare Cancer Network study.
AB  - Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant
      tumor with a poor prognosis. The aims of this retrospective study were to analyze
      the epidemiology, clinical characteristics, and treatment outcomes of these
      patients. Between 1994 and 2004, 24 patients with SCCE from several centers were
      reviewed for data on demographics, presenting symptoms, diagnosis, disease stage,
      type of treatment, and outcome. SCCE occurs in the sixth decade: median age
      (interquartile range [IQR]): 65 (59-69) years with a male predominance (63%). The
      most common complaining symptoms were rapidly progressive dysphagia (79%), weight
      loss (54%), and retrosternal/epigastric pain (46%). The tumor arises primarily in
      the middle (52%) or in the lower (35%) third of the esophagus. History of tobacco
      and alcohol exposure was present in 90% and 70% of case, respectively. Extensive
      disease was present in 13 cases (54%) at initial diagnosis. The overall median
      survival (IQR) was 11 (8-20) months for all 24 patients, and the 2-year overall
      survival was 25.1%. Four patients were alive more than 2 years after treatment.
      Chemotherapy increased the survival compared with symptomatic management in
      extensive disease (median survival [IQR]: 9.5 [6-14] vs. 6 [4-7] months, P=
      0.05). In limited disease, concurrent chemo-radiotherapy was more effective than
      non-concurrent treatment (median survival [IQR]: 36 [14-93] vs. 11 [9-15] months,
      P= 0.04). Two patients were treated by surgery and chemoradiation therapy with a
      survival of 35 and 66 months. Chemotherapy is the cornerstone of treatment of
      SCCE in all stage. For limited disease SCCE, concurrent chemo-radiotherapy is the
      primary choice compared with sequential approach. The role of surgery was not
      assessable in our study.

PMID- 21073625
TI  - Observations on use of montelukast in pediatric eosinophilic esophagitis:
      insights for the future.
AB  - Eosinophilic esophagitis is characterized by dense infiltration of the esophageal
      epithelium with eosinophils, typically accompanied by dysphagia. Effective
      therapies include the use of topical and systemic steroids as well as elimination
      diets. No previous reports have described the use of montelukast in the
      management of pediatric eosinophilic esophagitis. We retrospectively reviewed the
      charts of all patients with eosinophilic esophagitis followed in our pediatric
      center between 2000 and 2009. Those treated with montelukast were studied in
      detail. Study outcome was clinical response rate, defined by symptom (not
      histologic) improvement. Twenty-one patients with eosinophilic esophagitis were
      identified. Eight patients were maintained on montelukast (range 4-10 mg daily)
      after confirming the diagnosis of eosinophilic esophagitis histologically and
      failing to respond to a trial of proton pump inhibitor therapy. Three of eight
      patients had a clinical response (one had complete response and two with partial
      response) that could be attributed to montelukast. Four other patients responded
      clinically, but other therapies were concomitantly implemented. No side effects
      were reported with montelukast treatment with a mean follow-up duration of 32
      months. Five patients had remained on montelukast therapy at the time of the
      final follow-up. Montelukast has minimal risk of adverse reactions compared with
      steroid therapy and may offer clinical relief in a small subset of children with
      eosinophilic esophagitis. Histologic response could not be verified in this
      study. Prospective studies, using higher montelukast doses, may potentially play
      a role and should be considered for future investigation.

PMID- 21073626
TI  - Perioperative complications in children with Apert syndrome: a review of 509
      anesthetics.
AB  - OBJECTIVES: To perform a retrospective, anesthesia case note review in children
      with Apert Syndrome. AIM: To identify perioperative complications in this group
      of patients. BACKGROUND: Apert syndrome is a rare autosomal dominant disorder
      characterized by craniosynostosis, craniofacial anomalies, and severe symmetrical
      syndactyly (cutaneous and bony fusion) of the hands and feet. Children with this
      syndrome require general anesthetics for a number of different operations and
      procedures. Our institution has records of 71 children with Apert syndrome.
      Analysis of their general anesthetic records was undertaken, and the incidence of
      perioperative complications was investigated. METHODS: A retrospective case note
      review was performed on 61 children with Apert syndrome over a 14-year period.
      There were a total of 509 general anesthetics administered to these children
      during this period of time. RESULTS: There were a total of 31 perioperative
      respiratory complications occurring in 21 patients (6.1% of the total cases).
      Twenty-three of these complications were supraglottic airway obstruction (4.5% of
      total cases). CONCLUSIONS: We found there to be a low incidence of major
      perioperative major complications in this group of patients. Nevertheless, a
      significant proportion of these children have obstructive sleep apnoea and may
      develop supraglottic airway obstruction on induction and emergence from
      anesthesia due to the associated mid-face anatomical abnormalities.

PMID- 21073627
TI  - Decreasing candidaemia rate in abdominal surgery patients after introduction of
      fluconazole prophylaxis*.
AB  - Although abdominal surgery is an established risk factor for invasive
      candidiasis, the precise role of antifungal prophylaxis in these patients is not
      agreed upon. In 2007, fluconazole was added to the prophylactic antibiotic
      treatment for patients with gastrointestinal tract perforations or reoperation
      after colorectal surgery in two university hospitals in Copenhagen. Changes in
      candidaemia rates associated with this intervention were examined and potential
      interfering factors evaluated. Rates and clinical characteristics of candidaemias
      and other blood stream infections (BSIs) in abdominal surgery patients were
      compared before (1 January 2006 to 30 June 2007) and after the intervention (1
      January 2008 to 30 June 2009). The departments' activity was assessed by number
      of bed-days, admissions and surgical procedures, and the consumption of
      antifungals was analysed. The candidaemia rate decreased from 1.5/1000 admissions
      in the pre-intervention to 0.3/1000 admissions in the post-intervention period (p
      0.002). Numbers of BSIs and bed-days remained stable, and numbers of admissions
      and surgical procedures performed increased during the study period. Fluconazole
      consumption in the two abdominal surgery departments increased from 4.6 to 12.2
      defined daily doses per 100 bed-days (p <0.001), and 3.2 to 5.0 (p 0.01),
      respectively, but remained unchanged in the intensive care units. We could not
      detect any increase in fluconazole-resistant strains (14/29 pre- and 2/7 post
      intervention, p 0.43). The introduction of fluconazole prophylaxis was followed
      by a significantly decreased candidaemia rate. However, the observational study
      design does not allow conclusions regarding causality. No increase in resistance
      was detected, but follow-up was short and continuing surveillance is needed.

PMID- 21073628
TI  - Chagas disease in Latin American migrants: a Spanish challenge.
AB  - Chagas' disease affects millions in Latin America and is the leading cause of
      cardiomyopathy and death due to cardiovascular disease in patients aged 30-50
      years. As a consequence of immigration it has settled in several European
      countries, where besides imported cases, autochthonous infections arise through
      vertical transmission and blood/organ donation. All Latin American immigrants who
      attended our Unit were screened for T. cruzi infection (ELISA and IFAT +/- PCR).
      An ECG and echocardiogram were requested for all positive patients, and
      oesophageal manometry, barium swallow and barium enema were requested according
      to patient symptoms. All patients under 50 years without severe cardiac
      involvement and who had not received correct treatment previously were treated
      with benznidazole 5 mg/kg/day for 60 days. Patients were followed-up with
      serology and PCR 1 month after treatment ended and every 6 months thereafter. A
      total of 1146 Latin Americans were screened for T. cruzi (357 positive serology
      results). The typical patient profile was a Bolivian female, of rural origin, in
      her fourth decade of life, without evidence of visceral involvement. Treatment
      tolerance was poor, with 29.7% discontinuing treatment due to adverse reactions.
      Among those with adverse reactions (52%), the most frequent were cutaneous
      hypersensitivity (68.7%), gastrointestinal upset (20%) and nervous system
      disturbances (16.2%). T. cruzi infection is no longer limited to Latin America.
      Poor treatment tolerance can limit current treatment options. More
      epidemiological data are necessary to estimate the magnitude of a problem of
      great relevance for public health and health resource planning.

PMID- 21073629
TI  - Are all beta-lactams similarly effective in the treatment of methicillin
      sensitive Staphylococcus aureus bacteraemia?
AB  - Methicillin-sensitive Staphylococcus aureus (MSSA) is susceptible to many beta
      lactams. We compared cloxacillin and cefazolin, the first-line recommended
      antibiotics, and other beta-lactams in the treatment of MSSA bacteraemia. This
      was a retrospective cohort study. Included were adult patients with clinically
      significant MSSA bacteraemia treated with a beta-lactam that was started within
      48 h after blood cultures were taken. We separated between empirical treatment
      administered to the patient before receipt of final blood culture results and
      definitive treatment administered thereafter. Univariate and multivariable
      analyses for 30-day (empirical treatment) and 90-day (definitive treatment)
      mortality were conducted, including the type of beta-lactam administered to the
      patient. Five-hundred and forty-one patients were included for the analysis of
      empirical treatment and 498 patients alive at 7 days were evaluable for
      definitive treatment. Empirical treatment with cloxacillin or cefazolin (n = 131)
      was associated with lower 30-day mortality as compared with cefuroxime (n = 98, p
      0.058), ceftriaxone or cefotaxime (n = 194, p 0.008) and beta-lactam-beta
      lactamase combinations (n = 61, p 0.013), with adjusted odds ratios (OR) for
      death ranging from 1.98 to 2.68. Definitive treatment with cefazolin (n = 72) was
      not significantly different from cloxacillin (n = 281); adjusted OR for 90-day
      mortality 0.91 (95% confidence interval 0.47-1.77). Treatment with cefazolin both
      in the empirical and definitive periods was not significantly different from
      cloxacillin; adjusted OR 0.81 (95% confidence interval 0.18-3.62). Treatment of
      MSSA bacteraemia with cefazolin is not significantly different from treatment
      with cloxacillin, while treatment with other beta-lactams, including second and
      third generation cephalosporins, might be associated with higher mortality.

PMID- 21073630
TI  - Bacteraemia caused by beta-haemolytic streptococci in North Queensland: changing
      trends over a 14-year period.
AB  - Group A streptococci (GAS) are usually the predominant species in cases of
      bacteraemia caused by beta haemolytic streptococci (BHS). An increasing worldwide
      incidence of invasive disease from non-group A BHS has been reported. Little is
      known about the changing trends in invasive disease caused by BHS in Australia.
      North Queensland has a relatively large indigenous population, who experience
      significantly higher rates of group A-related disease than the non-indigenous
      population. This prospective study examined changing trends of disease from large
      colony BHS that group with A, B, C and G antisera over a 14-year period at the
      single large tertiary referral hospital in the area. We identified 392
      bacteraemic episodes caused by BHS. GAS were most commonly isolated (49%), with
      adjusted rates remaining stable over the period. There was a significant increase
      in the incidence of non-neonatal bacteraemia caused by group B streptococci (GBS)
      over the study period (r = 0.58; p 0.030), largely driven by infection in older,
      non-indigenous women. Rates of bacteraemia caused by group C streptococci also
      experienced a modest, but significant, increase over time (r = 0.67; p 0.009).
      GAS, which had no predominant emm type, were seen most commonly in indigenous
      subjects (52%). Mortality rates ranged from 3.2% (group G) to 10.3% (group C),
      with a rate of 7.9% associated with group A disease. The marked rise in GBS
      disease has been noted worldwide, but the relatively low incidence in indigenous
      Australian patients has not been described before, despite the burden of well
      recognized risk factors for GBS disease within this group.

PMID- 21073631
TI  - Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish
      and Italian infants.
AB  - In recent years, Staphylococcus aureus has become a common bowel colonizer in
      Swedish infants. We aimed to identify host factors that determine such
      colonization. Stool samples from 100 Italian and 100 Swedish infants were
      obtained on seven occasions during the first year of life and cultured
      quantitatively for S. aureus. In a subgroup of infants in each cohort, individual
      strains were identified by random amplified polymorphic DNA analysis.
      Colonization at each time-point was related to delivery mode, siblings in family
      and antibiotic treatment. In total, 66% of the Italian and 78% of the Swedish
      infants had S. aureus in their stools on at least one time-point (p 0.08) and 4%
      of Italian and 27% of Swedish infants were positive on at least six of the seven
      time-points investigated (p 0.0001). Most infants analysed regarding strain
      carriage harboured a single strain in their microbiota for several months. The S.
      aureus stool populations in colonized infants decreased from 10(7) to 10(4)
      colony-forming units/g between 1 week and 1 year of age in both cohorts. In
      multivariate analysis, the strongest predictor for S. aureus colonization was
      being born in Sweden (OR 3.4 at 1 week of age, p 0.002). Having (an) elder
      sibling(s) increased colonization at peak phase (OR 1.8 at 6 months, p 0.047).
      Antibiotic treatment was more prevalent among Italian infants and correlated
      negatively with S. aureus colonization at 6 months of age (OR 0.3, p 0.01). To
      conclude, S. aureus is a more common gut colonizer in Swedish than Italian
      infants, a fact that could not be attributed to feeding or delivery mode.

PMID- 21073632
TI  - Effect of fulvic and humic acids on performance, immune response and thyroid
      function in rats.
AB  - Effect of humic acid (HA) and fulvic acid (FA) on production parameters, immune
      response and thyroid function of rats were investigated in two experiments. First
      experiment: control or 0.1%, 0.2%, 0.4%, 0.8% HA- or FA-supplemented diets.
      Second experiment: control and 0.4% HA- or FA-supplemented diets. The feeding
      period lasted 26 days in both trials. No significant changes were observed in
      production parameters. Ovalbumine antibody titre of rats on HA- or FA
      supplemented diets showed dose-dependent (at 0.4% supplementation) and
      significant (p < 0.05) increase (350 and 418% respectively) over the control
      (100%). Dose-related increase of plasma TSH (r = 0.99), and decrease of the
      T(4)/T(3) ratio (r = -0.97) was observed in FA-supplemented rats. Second
      experiment: both FA and HA stimulated the immune response by the 14th day (mean
      values: control: 685.79; FA: 1131.37; HA: 1055.6099) and 26th day (control:
      544.31; FA: 1969.83; HA: 1600.00). No significant differences were noted with
      lymphocyte stimulation test. Diameter of the 'B'-dependent lymphoid tissues in
      the ileum and spleen were significantly (p < 0.05) larger in both the FA- and HA
      treated animals. Humic acid and FA supplementation resulted in strong humoral
      immune stimulation. Our data also indicate that FA content is responsible for the
      mild hypothyroid effect of humic substances.

PMID- 21073634
TI  - Corosolic acid inhibits glioblastoma cell proliferation by suppressing the
      activation of signal transducer and activator of transcription-3 and nuclear
      factor-kappa B in tumor cells and tumor-associated macrophages.
AB  - Tumor-associated macrophages (TAM) of M2 phenotype promote tumor proliferation
      and are associated with a poor prognosis in patients with glioblastoma. We
      screened the natural compounds possessing an inhibitory effect on M2 polarization
      in human monocyte-derived macrophages. Among 130 purified natural compounds
      examined, corosolic acid significantly inhibited the expression of CD163, one of
      the phenotype markers of M2 macrophages, and also suppressed the secretion of IL
      10, one of the anti-inflammatory cytokines preferentially produced by M2
      macrophages, thus suggesting that corosolic acid suppresses M2 polarization of
      macrophages. Furthermore, corosolic acid inhibited the proliferation of
      glioblastoma cells, U373 and T98G, and the activation of signal transducer and
      activator of transcription-3 (STAT3) and nuclear factor-kappa B (NF-kappaB) in
      both human macrophages and glioblastoma cells. These results indicate that
      corosolic acid suppresses the M2 polarization of macrophages and tumor cell
      proliferation by inhibiting both STAT3 and NF-kappaB activation. Therefore,
      corosolic acid might be a potential new tool for tumor prevention and therapy.

PMID- 21073635
TI  - Neural stem cell-like gene expression in a mouse ependymoma cell line transformed
      by human BK polyomavirus.
AB  - Ependymomas often show characteristics similar to those of neural stem cells in
      vivo and in vitro. However, few ependymoma cell lines that exhibit neural stem
      cell-like properties have been reported. In this study, we have characterized a
      novel cell line, designated Vn19, established from ependymoma that arose in mice
      inoculated intracerebrally with human BK polyomavirus. Transplanted Vn19 cells in
      nude mice ubiquitously expressed viral large T antigen in the nucleus and
      coexpressed neuronal and glial marker proteins in vivo. Remarkably, individual
      Vn19 cells in dispersed cultures simultaneously expressed marker proteins of
      neural stem cells (nestin, Bmi1, CD133), neurons (betaIII tubulin, neurofilament
      M) and glial cells (glial fibrillary acidic protein, A2B5, S100beta, O4).
      Ubiquitous and homogenous expression of these multilineage marker proteins was
      also observed in cloned Vn19 cells. The Vn19 cells formed neurosphere-like
      aggregates when cultured in the presence of growth factors. Quantitative RT-PCR
      analysis revealed that expression of mRNA for nestin, neurofilament-H and glial
      fibrillary acidic protein significantly increased in Vn19 cells cultured under
      growth factor-deprived conditions. Among MAGE (melanoma antigen) family genes,
      MAGE-A (A1-8), MAGE-B (B1-3), MAGE-D1, MAGE-E1, MAGE-G1 (necdin-like 2) and MAGE
      H1 were expressed in the Vn19 cells, in which neither necdin nor MAGEL2 was
      detectable. These results suggest that this murine ependymoma cell line
      recapitulates the gene expression profile in ependymal cells undergoing malignant
      transformation.

PMID- 21073636
TI  - Catechols in post-mortem brain of patients with Parkinson disease.
AB  - BACKGROUND: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of
      dopamine, is the focus of the 'catecholaldehyde hypothesis' about the
      pathogenesis of Parkinson disease. This study explored whether DOPAL is
      detectable in human striatum - especially in the putamen (Pu), the main site of
      dopamine depletion in Parkinson disease - and is related to other neurochemical
      indices of catecholamine stores and metabolism in Parkinson disease. METHODS:
      Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue
      from patients with pathologically proven end-stage Parkinson disease (N=15) and
      control subjects (N=14) of similar age with similar post-mortem intervals.
      RESULTS: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and
      dihydroxyphenylacetic acid both across all subjects and within the Parkinson
      disease and control groups. Pu dopamine was decreased by 93% and
      dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller
      decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and
      dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu
      DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times
      control (P=0.03 each). The main catecholamine in Ctx was norepinephrine, which
      was decreased by 51% in Parkinson disease patients. CONCLUSIONS: Correlated
      decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease
      reflect severe loss of Pu dopamine stores, which seems more extensive than loss
      of Pu norepinephrine or Cd dopamine stores. Increased Pu
      DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased
      detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic
      DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.

PMID- 21073637
TI  - Associations of tryptophan hydroxylase gene polymorphisms with irritable bowel
      syndrome.
AB  - BACKGROUND: Alterations in serotonin (5-HT) are suspected in the pathophysiology
      of irritable bowel syndrome (IBS). Tryptophan hydroxylase (TPH) is the rate
      limiting enzyme in the biosynthesis of serotonin and has two isoforms: TPH1 and
      TPH2. Genetic variants in both genes have been studied in various disorders
      related to serotonin dysregulation. The aim of this study was to examine whether
      TPH gene variants were associated with IBS and IBS-related gastrointestinal (GI)
      symptoms. METHODS: Five single nucleotide polymorphisms (SNPs) from the TPH1 and
      one SNP from the TPH2 were genotyped in 199 IBS patients and 79 healthy controls.
      All subjects were Caucasian women of European origin. Irritable bowel syndrome
      patients filled in a daily diary with five GI symptoms and stool characteristics
      for 28 days. KEY RESULTS: The TPH1 SNPs showed no association with the diagnosis
      of IBS. However, among IBS patients, all five TPH1 SNPs showed some association
      with diarrhea and loose type of stool consistency, with P-values rating from 0.01
      to 0.20. The TPH2 SNP showed a trend towards a reduced risk of IBS and possible
      associations with stool characteristics, both hard and loose stools. However, no
      P-values were less than the conservative multiple-comparison-adjusted threshold
      of 0.001 and hence these results must be interpreted cautiously. CONCLUSIONS &
      INFERENCES: This study is the first to assess associations of TPH gene variants
      with IBS-related GI symptoms and stool characteristics. The possible association
      of TPH gene variants with diarrhea needs to be verified in an independent sample.

PMID- 21073638
TI  - Spatially disaggregated disease transmission risk: land cover, land use and risk
      of dengue transmission on the island of Oahu.
AB  - Vector-borne diseases persist in transmission systems that usually comprise
      heterogeneously distributed vectors and hosts leading to a highly heterogeneous
      case distribution. In this study, we build on principles of classical
      mathematical epidemiology to investigate spatial heterogeneity of disease risk
      for vector-borne diseases. Land cover delineates habitat suitability for vectors,
      and land use determines the spatial distribution of humans. We focus on the risk
      of exposure for dengue transmission on the Hawaiian island of Oahu, where the
      vector Aedes albopictus is well established and areas of dense human population
      exist. In Hawai'i, dengue virus is generally absent, but occasionally flares up
      when introduced. It is therefore relevant to investigate risk, but difficult to
      do based on disease incidence data. Based on publicly available data (land cover,
      land use, census data, surveillance mosquito trapping), we map the spatial
      distribution of vectors and human hosts and finally overlay them to produce a
      vector-to-host ratio map. The resulting high-resolution maps indicate a high
      spatial variability in vector-to-host ratio suggesting that risk of exposure is
      spatially heterogeneous and varies according to land cover and land use.

PMID- 21073639
TI  - Prevalence of intestinal parasites among school children in northern districts of
      West Bank-Palestine.
AB  - OBJECTIVES: To assess the prevalence of intestinal parasite infections in
      northern districts of West Bank, Palestine and to determine associated
      sociodemographic factors. METHODS: Random sampling of schoolchildren from rural
      and urban areas was carried out. Participants provided faecal samples and
      answered a questionnaire about their demographics and hygiene habits. Faecal
      samples underwent microscopy and PCR to screen for protozoan and helminths.
      RESULTS: Seven hundred and thirty-five samples were collected from children aged
      9.5 years on average. The overall prevalence of parasitic infection was 22.2%.
      The rates of infections with amoeba, Giardia intestinalis, Entrobius vermicularis
      and Ascaris lumbricoides were 9.7%, 4.1%, 1.6% and 3.8%, respectively. Real-time
      PCR was performed to differentiate between Entamoeba histolytica and Entamoeba
      dispar. Results showed that 14% of samples positive with microscopy for amoeba
      were positive for E. histolytica. There was no significant association between
      sex and rates of infections (P-value > 0.05). There were, however, significant
      association between parasite infections and parents' education, place of
      residence, washing hands habits (P-value > 0.05). No significant association was
      found with number of family members or eating in school canteens (P-value >
      0.05). CONCLUSIONS: Intestinal parasite infections are endemic in West Bank.
      Interventions such as health education and sanitation are needed.

PMID- 21073640
TI  - A quasi-experimental evaluation of a community-based art therapy intervention
      exploring the psychosocial health of children affected by HIV in South Africa.
AB  - OBJECTIVES: To evaluate the efficacy of the Make A Difference about Art
      programme, a community art programme in South Africa for children affected by HIV
      and AIDS, which aims to reduce psychosocial problems by increasing self-esteem,
      self-efficacy and HIV insight. METHODS: A quasi-experimental cross-sectional post
      intervention survey of 297 children aged 8-18 years (177 programme attendees and
      a control group of 120). Participants completed an inventory comprising
      standardized, validated psychosocial measures of depression, emotional and
      behavioural problems, self-esteem and self-efficacy and key sociodemographic
      variables potentially relevant as risk and protective factors. RESULTS: Attending
      the intervention was predictive of significantly higher self-efficacy, but was
      not associated with differences in self-esteem, depression, or
      emotional/behavioural problems. This association remained in the multivariate
      analysis, controlling for potential confounders. Double parental death exerted a
      powerful effect on child psychosocial health, eliminating the association between
      intervention attendance and higher self-efficacy. However, an interaction was
      found between bereavement status and intervention attendance on child self
      efficacy, indicating that the intervention programme may ameliorate some of the
      psychosocial vulnerabilities associated with becoming an orphan. Other key risk
      factors for poor psychosocial health in this sample were AIDS-related stigma and
      community and household violence. Social connection emerged as a key protective
      factor. CONCLUSIONS: Our findings suggest that such interventions may offer
      opportunities to increase the self-efficacy of vulnerable children to protect
      their psychological health.

PMID- 21073641
TI  - Soil fungal pathogens and the relationship between plant diversity and
      productivity.
AB  - One robust result from many small-scale experiments has been that plant community
      productivity often increases with increasing plant diversity. Most frequently,
      resource-based or competitive interactions are thought to drive this positive
      diversity-productivity relationship. Here, we ask whether suppression of plant
      productivity by soil fungal pathogens might also drive a positive diversity
      productivity relationship. We created plant assemblages that varied in diversity
      and crossed this with a +/- soil fungicide treatment. In control (non-fungicide
      treated) assemblages there was a strong positive relationship between plant
      diversity and above-ground plant biomass. However, in fungicide-treated
      assemblages this relationship disappeared. This occurred because fungicide
      increased plant production by an average of 141% at the lower ends of diversity
      but boosted production by an average of only 33% at the higher ends of diversity,
      essentially flattening the diversity-productivity curve. These results suggest
      that soil pathogens might be a heretofore unappreciated driver of diversity
      productivity relationships.

PMID- 21073642
TI  - Genotypic characterization to identify markers associated with putative
      hypervirulence in Swedish Escherichia coli O157:H7 cattle strains.
AB  - AIMS: To establish whether investigated subtyping methods could identify any
      specific characteristics that distinguish Swedish VTEC O157:H7 strains isolated
      from cattle farms associated with human enterohaemorrhagic Escherichia coli
      (EHEC) cases from cattle strains isolated in prevalence studies. METHODS AND
      RESULTS: Strains (n = 32) isolated in a dairy herd prevalence study and strains
      isolated from farms associated with human cases (n = 13) were subjected to
      typing. Partial sequencing of the vtx(2) genes could not identify any unique
      variants of vtx(2) or vtx(2c) in strains associated with human cases. A specific
      variant of VTEC O157:H7, which was overrepresented among farms associated with
      human cases (P = 0.01), was by two different single-nucleotide-polymorphism (SNP)
      assays identified as clade 8, a subgroup of VTEC O157:H7 strains considered to be
      putatively hypervirulent. Multi-locus variable number tandem repeat analysis
      (MLVA) typing of all strains produced similar results as pulsed-field gel
      electrophoresis (PFGE) typing regarding clustering of the strains, but MLVA
      distinguished slightly better among strains than PFGE. CONCLUSION: In Sweden,
      VTEC O157:H7 strains from the putatively hypervirulent clade 8 are
      overrepresented among isolates from cattle farms associated with human cases
      compared with VTEC O157:H7 strains isolated in prevalence studies. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Real-time PCR SNP typing for clade 8 can be used to
      identify cattle farms that are at higher risk of causing EHEC infections in
      humans.

PMID- 21073643
TI  - Venation networks and the origin of the leaf economics spectrum.
AB  - The leaf economics spectrum describes biome-invariant scaling functions for leaf
      functional traits that relate to global primary productivity and nutrient
      cycling. Here, we develop a comprehensive framework for the origin of this leaf
      economics spectrum based on venation-mediated economic strategies. We define a
      standardized set of traits - density, distance and loopiness - that provides a
      common language for the study of venation. We develop a novel quantitative model
      that uses these venation traits to model leaf-level physiology, and show that
      selection to optimize the venation network predicts the mean global trait-trait
      scaling relationships across 2548 species. Furthermore, using empirical venation
      data for 25 plant species, we test our model by predicting four key leaf
      functional traits related to leaf economics: net carbon assimilation rate, life
      span, leaf mass per area ratio and nitrogen content. Together, these results
      indicate that selection on venation geometry is a fundamental basis for
      understanding the diversity of leaf form and function, and the carbon balance of
      leaves. The model and associated predictions have broad implications for
      integrating venation network geometry with pattern and process in ecophysiology,
      ecology and palaeobotany.

PMID- 21073644
TI  - Niche construction in the light of niche theory.
AB  - Ecological niche construction, the process whereby an organism improves its
      environment to enhance its growth and persistence, is an important missing
      element of niche theory. Niche theory has mainly focused on niche-deteriorating
      processes, such as resource consumption, predation and competition, which have
      negative effects on population growth. Here, we integrate niche construction
      explicitly into modern niche theory. We use a graphical approach to analyse how a
      species' niche-improving impacts interplay with niche-deteriorating impacts to
      modify its response to the environment. In a model of two consumers that compete
      for one limiting resource and one predator, we show how niche construction
      modifies the traditional niche-deteriorating impacts of its agent or of competing
      species, and hence the potential for species coexistence. By altering the balance
      between intraspecific and interspecific competitive effects, niche construction
      can either generate net interspecific facilitation or strengthen interspecific
      competition. The adaptive benefit derived from niche construction also strongly
      affects the realized niche of a niche-constructing species.

PMID- 21073645
TI  - Changing trends in polypoid colorectal cancer diagnosed by colonoscopy.
AB  - AIM: This study analysed trends in polypoid colorectal cancer (PCRC) diagnosed by
      colonoscopy during the period 1995-2008 and compared the patterns observed in the
      years 2005-2008 with 1995-1998. METHOD: In the period 1995-2008, 24,245
      colonoscopies were performed and 1041 patients with PCRC were diagnosed:
      pediculated (n = 220) or sessile (n = 821). RESULTS: The mean age at diagnosis
      was 68.3 +/- 11.6 years. Males were more likely to have PCRC (males 62.6%vs
      females 37.4%; P < 0.0001). Significantly more pediculated PCRCs were located in
      the distal colon (P < 0.001). In the 2005-2008 period the prevalence of PCRC
      among patients undergoing colonoscopy decreased, the number of polypectomies
      increased significantly (P < 0.0001) and the pediculated PCRC location changed,
      with a significant increase in right-sided lesions. CONCLUSION: The prevalence of
      PCRC in patients undergoing colonoscopy decreased, with a significant increase in
      the number of polypectomies in the last decade. Pediculated PCRCs were more often
      located in the left colon and sessile PCRCs in the right colon. From the period
      1995-1998 to 2005-2008 the location of pediculated PCRCs changed, with an
      increase in right-sided lesions.

PMID- 21073646
TI  - The diagnostic accuracy of chromoendoscopy for dysplasia in ulcerative colitis:
      meta-analysis of six randomized controlled trials.
AB  - AIM: The diagnostic accuracy of chromoendoscopy for dysplasia in ulcerative
      colitis (UC) was systematically evaluated. METHOD:   Original studies in any
      language were searched from PubMed and Embase. Meta-analysis of prospective
      studies that compared chromoendoscopy with histological diagnosis was carried
      out. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated
      for each study and pooled together; summary receiver operating characteristic
      (ROC) and subgroup analyses were performed, while the quality of the study and
      heterogeneity were assessed. RESULTS: Six randomized controlled trials were
      included, which used methylene blue or indigo carmine dye spray. The meta
      analysis demonstrated a pooled sensitivity of 83.3% (95% confidence interval
      (CI), 35.9-99.6%), specificity of 91.3% (95% CI, 43.8-100%), and DOR of 17.544
      (95% CI, 1.245-247.14). Subgroup analyses revealed that both the methylene blue
      dye spray subgroup and the unspecified endoscopist subgroup include the same
      studies, and their pooled sensitivity and specificity were 0.737 and 0.917,
      respectively. The other subgroup, which used indigo carmine dye spray, had
      overall higher sensitivity (0.930) and lower specificity (0.910). CONCLUSION:
      Chromoendoscopy has medium to high sensitivity and a high diagnostic accuracy for
      dysplastic lesions in UC.

PMID- 21073647
TI  - Prognostic factors for survival after curative resection of Dukes' B colonic
      cancer.
AB  - AIM: Data on the prognostic factors for survival in patients with locally
      advanced, node-negative colon cancer are limited. This study aimed to determine
      which factors might predict survival in patients with Dukes' B (T3 or T4, N0)
      colon cancer. METHOD: One hundred and eighty (93 male; median age 75 [range, 38
      96] years) consecutive patients who had resection of a primary Dukes' B (on final
      histopathological analysis) colonic cancer between 1998 and 2003 were studied. No
      patient received neoadjuvant chemotherapy. Multivariate Cox regression modelling
      was used to assess the prognostic value of variables. Median follow up was 85 (60
      125) months. RESULTS: Thirteen (7%) patients had a perforation at presentation.
      The median distance from tumour to the nearest longitudinal resection margin was
      6 (0.3-27) cm. One hundred and twenty-four (69%) patients had a lymph node yield
      of 12 or more nodes. Actual 5-year survival was 59%. On multivariate regression
      analysis, tumour perforation (perforation vs no perforation, 5-year survival,
      23%vs 61%; hazard ratio (HR), 3.7; 95% confidence interval (CI), 1.6-8.4; P =
      0.002), tumour-to-margin distance (< 5 cm vs >= 5 cm, 48%vs 65%; HR, 1.7; 95% CI,
      1.1-2.7; P = 0.039) and older age (>= 75 years vs < 75 years, 45%vs 72%; HR, 3;
      95% CI, 1.8-5; P < 0.001) were independent significant variables. CONCLUSION: A
      lymph node yield of 12 or more nodes is not a significant prognostic factor for
      survival after resection of Dukes' B colonic cancer. Patients with tumour
      perforation or limited resection have worse prognosis.

PMID- 21073648
TI  - Inertia: the discrepancy between individual and common good in dispersal and
      prospecting behaviour.
AB  - The group selection debate of the 1960s made it clear that evolution does not
      necessarily increase population performance. Individuals can be selected to have
      traits that diminish a common good and make population persistence difficult. At
      the extreme, the discrepancy between levels of selection is predicted to make
      traits evolve towards values at which a population can no longer persist
      (evolutionary suicide). Dispersal and prospecting are prime examples of traits
      that have a strong influence on population persistence under environmental and
      demographic stochasticity. Theory predicts that an 'optimal' dispersal strategy
      from a population point of view can differ considerably from that produced by
      individual-level selection. Because dispersal is frequently risky or otherwise
      costly, individuals are often predicted to disperse less than would be ideal for
      population performance (persistence or size). We define this discrepancy as
      'inertia' and examine current knowledge of its occurrence and effects on
      population dynamics in nature. We argue that inertia is potentially widespread
      but that a framework is currently lacking for predicting precisely the extent to
      which it has a real influence on population persistence. The opposite of inertia,
      'hypermobility' (more dispersal by individuals than would maximize population
      performance) remains a possibility: it is known that highest dispersal rates do
      not lead to best expected population performance, and examples of such high
      dispersal evolving exist at least in the theoretical literature. We also show, by
      considering prospecting behaviour, that similar issues arise in species with
      advanced cognitive and learning abilities. Individual prospecting strategies and
      the information acquired during dispersal are known to influence the decisions
      and therefore the fate of individuals and, as a corollary, populations. Again,
      the willingness of individuals to sample environments might evolve to levels that
      are not optimal for populations. This conflict can take intriguing forms. For
      example, better cognitive abilities of individuals may not always lead to better
      population-level performance. Simulation studies have found that 'blind'
      dispersal can lead to better connected metapopulations than cognitively more
      advanced habitat choice rules: the latter can lead to too many individuals
      sticking to nearby safe habitat. The study of the mismatch between individual and
      population fitness should not be a mere intellectual exercise. Population
      managers typically need to take a population-level view of performance, which may
      necessitate human intervention if it differs from what is selected for. We
      conclude that our knowledge of inertia and hypermobility would advance faster if
      theoretical studies--without much additional effort--quantified the population
      consequences of the evolving traits and compared this with hypothetical (not
      selectively favoured) dispersal rules, and if empirical studies were similarly
      conducted with the differing levels of selection in mind.

PMID- 21073649
TI  - Angiogenesis in chronic liver disease and its complications.
AB  - Nowadays, liver cancer, cirrhosis and other liver-related diseases are the fifth
      most common cause of mortality in the UK. Furthermore, chronic liver diseases
      (CLDs) are one of the major causes of death, which are still increasing year-on
      year. Therefore, knowledge about the pathophysiology of CLDs and its
      complications is of uttermost importance. The goal of this review is to clarify
      the role of angiogenesis in the disease progression of various liver diseases.
      Looking closer at the pathophysiology of portal hypertension (PH), fibrosis,
      cirrhosis, non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma
      (HCC), we find that angiogenesis is a recurring factor in the disease
      progression. In PH, several factors involved in its pathogenesis, such as
      hypoxia, oxidative stress, inflammation and shear stress are potential mediators
      for the angiogenic response. The progression from fibrosis to cirrhosis, the end
      point of CLDs, is distinguished by a prolonged inflammatory and fibrogenic
      process that leads to an abnormal angioarchitecture distinctive for cirrhosis. In
      several stages of NASH, a link might be made between the disease progression and
      hepatic microvasculature changes. HCC is one of the most vascular solid tumours
      in which angiogenesis plays an important role in its development, progression and
      metastasis. The close relationship between the progression of CLDs and
      angiogenesis emphasises the need for anti-angiogenic therapy as a tool for
      blocking or slowing down the disease progression. The fact that angiogenesis
      plays a pivotal role in CLDs gives rise to new opportunities for treating CLDs
      and its complications.

PMID- 21073650
TI  - Anti-oxidants do not prevent bile acid-induced cell death in rat hepatocytes.

PMID- 21073651
TI  - Expression of common housekeeping genes is affected by disease in human hepatitis
      C virus-infected liver.
AB  - BACKGROUND: Comparative gene expression is commonly determined with reference to
      the expression of a housekeeping gene (HKG), the level of which is assumed to be
      unregulated. There are little data to date on the effect of disease on the
      expression of classic HKGs in hepatitis C virus (HCV)-infected human liver. AIMS:
      To identity HKGs stable across a wide spectrum of disease in human HCV-infected
      liver. METHODS: beta-Actin, hypoxanthine phosphoribosyltransferase 1 (HPRT1),
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), splicing factor arginine/serine
      rich 4, beta-glucuronidase and 18S ribosomal RNA (18S rRNA) were measured by real
      time polymerase chain reaction in liver biopsy tissue. Samples were categorised
      for inflammation, fibrosis and steatosis, and allocated into groups with mild or
      severe liver disease. Values were analysed using Spearman's rank correlation,
      NormFinder, BestKeeper and geNorm programs. RESULTS: All genes performed well in
      the samples of patients with low disease activity, but HPRT1, beta-actin, GAPDH
      and 18S rRNA ranked poorly in samples with severe fibrosis or inflammation.
      CONCLUSIONS: Our results indicate that liver disease affects the expression of
      common HKGs and that beta-glucuronidase and splicing factor arginine/serine-rich
      4 are the most stable HKGs from this group for studies of gene expression in HCV
      infected human liver.

PMID- 21073652
TI  - Hemodynamic consequences of pulmonary embolism: a rebuttal.

PMID- 21073653
TI  - Identification of the UDP-glucosyltransferase gene UGTA1, responsible for the
      first glucosylation step in the sophorolipid biosynthetic pathway of Candida
      bombicola ATCC 22214.
AB  - Candida bombicola ATCC 22214 is applied commercially for the production of
      sophorolipids from renewable resources such as vegetable oils or waste streams.
      Although much research has been performed on optimization of fermentation
      conditions and on the influence of feed source and process parameters on
      sophorolipid structures and yields, the metabolic pathway of these important
      bioproducts remains unclear. Here, we identify a glucosyltransferase gene UGTA1
      and show that the gene product is responsible for the first glucosylation step in
      the biosynthetic pathway of sophorolipids. Moreover, we provide evidence that the
      second glucosylation step is catalysed by a different glucosyltransferase that
      acts independently from the first. Therefore, the biosynthesis of sophorolipids
      by C. bombicola involves two glucosyltransferases that act in a stepwise manner.
      The UGTA1 gene described here is the first identified gene with a clear function
      in sophorolipid production by this economically important yeast.

PMID- 21073654
TI  - Role of HLA-G and NCR in protection of umbilical cord blood haematopoietic stem
      cells from NK cell mediated cytotoxicity.
AB  - Allogeneic umbilical cord blood haematopoietic stem cells (UCB-HSCs) can be
      transplanted into a host with the intact innate immunity with limited immuno
      reaction, although the mechanisms remain unclear. The present studies aimed at
      investigating potential mechanisms of allogeneic UCB-HSCs escape from the
      cytolysis of natural killer (NK) cells. We compared UCB-HSCs ability to protect
      from NK-mediated cytotoxicity with peripheral blood or bone marrow haematopoietic
      stem cells (PB-HSCs and BM-HSCs). HSCs expressed lower levels of natural
      cytotoxicity receptor ligands including NKp30L, NKp44L and NKp46L than monocytes.
      Blocking these ligands respectively or in combination could increase the
      resistance of HSCs against NK cell mediated cytotoxicity. High expression of HLA
      G was noticed on UCB-HSCs, rather than PB-HSCs or BM-HSCs, whereas blockade of
      HLA-G significantly elevated NK cell mediated cytolysis to UCB-HSCs. Thus, we
      conclude that natural cytotoxicity receptors and HLA-G on HSCs may contribute to
      the escape from NK cells, and activate and inhibitory NK cell receptors and their
      ligands can be novel therapeutic targets in cell transplantation.

PMID- 21073655
TI  - Suppression of NADPH oxidase 2 substantially restores glucose-induced dysfunction
      of pancreatic NIT-1 cells.
AB  - Defects in insulin secretion by pancreatic cells and/or decreased sensitivity of
      target tissues to insulin action are the key features of type 2 diabetes. It has
      been shown that excessive generation of reactive oxygen species (ROS) is linked
      to glucose-induced beta-cell dysfunction. However, cellular mechanisms involved
      in ROS generation in beta-cells and the link between ROS and glucose-induced beta
      cell dysfunction are poorly understood. Here, we demonstrate a key role of NADPH
      oxidase 2 (NOX2)-derived ROS in the deterioration of beta-cell function induced
      by a high concentration of glucose. Sprague-Dawley rats were fed a high-fat diet
      for 24 weeks to induce diabetes. Diabetic rats showed increased glucose levels
      and elevated ROS generation in blood, but decreased insulin content in pancreatic
      beta-cells. In vitro, increased ROS levels in pancreatic NIT-1 cells exposed to
      high concentrations of glucose (33.3 mmol.L(-1)) were associated with elevated
      expression of NOX2. Importantly, decreased glucose-induced insulin expression and
      secretion in NIT-1 cells could be rescued via siRNA-mediated NOX2 reduction.
      Furthermore, high glucose concentrations led to apoptosis of beta-cells by
      activation of p38MAPK and p53, and dysfunction of beta-cells through phosphatase
      and tensih homolog (PTEN)-dependent Jun N-terminal kinase (JNK) activation and
      protein kinase B (AKT/PKB) inhibition, which induced the translocation of
      forkhead box O1 and pancreatic duodenal homeobox-1, followed by reduced insulin
      expression and secretion. In conclusion, NOX2-derived ROS could play a critical
      role in high glucose-induced beta-cell dysfunction through PTEN-dependent JNK
      activation and AKT inhibition.

PMID- 21073656
TI  - The antagonistic effect of hydroxyl radical on the development of a
      hypersensitive response in tobacco.
AB  - Reactive oxygen species (ROS) are important signalling molecules in living cells.
      It is believed that ROS molecules are the main triggers of the hypersensitive
      response (HR) in plants. In the present study of the effect of riboflavin, which
      is excited to generate ROS in light, on the development of the HR induced by the
      elicitin protein ParA1 in tobacco (Nicotiana tabacum), we found that the extent
      of the ParA1-induced HR was diminished by hydroxyl radical (OH*), a type of ROS.
      As compared with the zones treated with ParA1 only, the HR symptom in the zones
      that were infiltrated with ParA1 plus riboflavin was significantly diminished
      when the treated plants were placed in the light. However, this did not occur
      when the plants were maintained in the dark. Trypan blue staining and the ion
      leakage measurements confirmed HR suppression in the light. Further experiments
      proved that HR suppression is attributed to the involvement of the photoexcited
      riboflavin, and that the suppression can be eliminated with the addition of
      hydrogen peroxide scavengers or OH* scavengers. Fenton reagent treatment and EPR
      measurements demonstrated that it is OH* rather than hydrogen peroxide that
      contributes to HR suppression. Accompanying the endogenous OH* formation,
      suppression of the ParA1-induced HR occurred in the tobacco leaves that had been
      treated with high-level abscisic acid, and that suppression was also removed by
      OH* scavengers. These results offer evidence that OH*, an understudied and little
      appreciated ROS, participates in and modulates biologically relevant signalling
      in plant cells.

PMID- 21073657
TI  - The calcium-sensing receptor mediates hypoxia-induced proliferation of rat
      pulmonary artery smooth muscle cells through MEK1/ERK1,2 and PI3K pathways.
AB  - Activation of the calcium-sensing receptor (CaSR) leads to an increase of
      intracellular calcium concentration and alteration of cellular activities. High
      level of intracellular calcium is involved in hypoxia-induced proliferation of
      pulmonary arterial smooth muscle cells (PASMCs). However, whether the CaSR is
      expressed in PAMSCs and is related to the hypoxia-induced proliferation of PASMCs
      is unclear. In this study, the expression and distribution of CaSRs were detected
      by RT-PCR, western blotting and immunofluorescence; the intracellular
      concentration of free calcium ([Ca(2+) ](i) ) was determined by confocal laser
      scanning microscopy; cell proliferation was tested using an MTT and BrdU
      incorporation assay; cell cycle analysis was carried out using a flow cytometric
      assay; and the expression of proliferating cell nuclear antigen (PCNA),
      extracellular signal-regulated protein kinase 1,2 (ERK1,2) and AKT were analysed
      by western blotting. We observed that both CaSR mRNA and protein were expressed
      in rat PASMCs. Lowering of oxygen from 21% to 2.5% led to increased [Ca(2+) ](i)
      and CaSR expression. This condition of hypoxia also stimulated PASMCs
      proliferation accompanying with increased phosphorylation of ERK1,2 and AKT.
      GdCl(3) (an agonist of CaSR) or NPS2390 (an antagonist of CaSR) amplified or
      weakened the effect of hypoxia, respectively. PD98059 (a MEK1 inhibitor) or
      LY294002 (a PI3K inhibitors) decreased the up-regulation of PCNA expression and
      the increase of the cell proliferation index induced by hypoxia and GdCl(3) in
      PASMCs. Our results suggest that CaSR is expressed in rat PASMCs, and that CaSR
      activation through MEK1/ERK1,2 and PI3 kinase pathways is involved in hypoxia
      induced proliferation of PASMCs.

PMID- 21073658
TI  - Epistaxis in weekly paclitaxel regimen: Is it really related to schedule?

PMID- 21073659
TI  - In vitro and in vivo inhibition of MRP gene expression and reversal of multidrug
      resistance by siRNA.
AB  - Clinical drug resistance to chemotherapeutic agents is one of the major
      hindrances in the treatment of human cancers. One mechanism by which a living
      cell can achieve multidrug resistance (MDR) is via the active efflux of a broad
      range of anti-cancer drugs through the cellular membrane by MDR proteins. Over
      expression of multidrug resistance-associated protein 1 (MRP1) is one of the
      important MDR phenotypes. RNA interference (RNAi) is a fundamental cellular
      mechanism for silencing gene expression that can be harnessed for the development
      of new drugs. In our study, by using lipofectamin(TM) 2000 (Invitrogen, Carlsbad,
      CA, USA) in vitro and electric pulse in vivo to delivery siRNA, we successfully
      inhibited MRP1 both at mRNA and protein level as determined by reverse
      transcription-PCR and western blot or immunohistochemistry. Furthermore, the
      efficacy of chemotherapeutic drugs (epirubicin) to tumour cells dramatically
      improved both in vivo and in vitro. These studies demonstrate that through
      efficient delivery siRNA, MRP1-mediated MDR can be reversed and siRNA can be used
      for further study in clinical cancer therapy.

PMID- 21073660
TI  - Interaction of nitric oxide and the cytochrome P-450 system on blood pressure and
      renal function in the rat: dependence on sodium intake.
AB  - AIM: Interaction was examined of nitric oxide (NO) and cytochrome P-450 (CYP-450)
      dependent arachidonic acid derivatives, 20-HETE and EETs, in control of arterial
      pressure (MABP) and renal function. Modification of this interaction by changing
      sodium intake was also studied. METHODS: On low, standard or high Na diet (LS,
      STD and HS rats respectively) effects of sequential blockade of NO synthases
      (NOS) and CYP-450 enzyme activity on MABP, renal blood flow (RBF, Transonic
      probe), renal medullary perfusion (MBF, laser-Doppler technique), medullary
      tissue NO (selective electrode) and renal excretion were examined in
      anaesthetized rats. All NOS were blocked with N(pi) -nitro-l-arginine methyl
      ester (l-NAME), the neuronal NOS with S-methyl-l-thiocitrulline (SMTC), and CYP
      450 with 1-aminobenzotriazole (ABT). RESULTS: In each diet group the baseline
      MABP was highest in rats pre-treated with l-NAME. CYP-450 inhibition
      significantly decreased MABP only in LS (-9%) and HS rats (-22%) pre-treated with
      l-NAME. This MABP decrease correlated directly with the dietary sodium content (r
      = 0.644, P < 0.001). CYP-450 inhibition decreased RBF in LS and HS rats (not in
      HS pre-treated with l-NAME). Acute exclusion of CYP-450 significantly increased
      MBF only in STD, SMTC pre-treated rats; in HS group it significantly increased
      medullary tissue NO by about 1.0 nA. The post-ABT changes in renal excretion
      occurred in LS and HS rats, irrespective of the status of NO synthesis.
      CONCLUSIONS: Both NO- and CYP-450-dependent agents contribute to blood pressure
      and kidney function control, however, the role of 20-HETE and EETs becomes
      crucial only under conditions of high sodium intake or after NOS inhibition.

PMID- 21073661
TI  - Estrogen prevents beta-amyloid inhibition of sympathetic alpha7-nAChR-mediated
      nitrergic neurogenic dilation in porcine basilar arteries.
AB  - AIM: beta-amyloid peptides (Abetas) have been shown to block cerebral nitrergic
      neurogenic vasodilation by blocking sympathetic alpha7-nAChRs, and that oestrogen
      prevents Abeta-induced neurotoxicity. We examined whether Abeta-inhibition of
      alpha7-nAChR-mediated cerebral nitrergic vasodilation was prevented by oestrogen.
      METHODS: Effects of Abeta and 17beta-oestradiol on neurogenic nitrergic
      vasodilation in isolated porcine basilar arteries were examined using wire
      myography. Drug effects on nicotine- and choline-induced calcium influx and
      inward currents in porcine cultured superior cervical ganglion (SCG) were
      investigated using confocal microscopy and patch-clamp techniques respectively.
      RESULTS: Precontracted endothelium-denuded basilar arteries relaxed exclusively
      upon transmural nerve stimulation (TNS, 8 Hz), and applications of nicotine (100
      MUm) or choline (1 mm), which was sensitive to nitro-L-arginine (L-NNA, 30 MUm)
      and tetrodotoxin (0.3 MUm). The relaxation induced by nicotine and choline but
      not that by TNS was blocked reversibly by Abeta(1-40) in a concentration
      dependent manner. Abeta(1-40) also reversibly blocked nicotine- and choline
      induced increase of calcium influx and inward currents in the SCG neurons. Abeta
      inhibition of nicotine- and choline-induced alpha7-nAChR-mediated nitrergic
      vasodilation and inward currents was prevented by 17beta-oestradiol (10 MUm), but
      not by alpha-oestradiol (10 MUm) or testosterone (10 MUm). CONCLUSION: These
      results provide further evidence supporting that Abeta is an antagonist for the
      alpha7-nAChR found on post-ganglionic sympathetic adrenergic nerve terminals
      originating in the SCG. Abeta can cause constriction of cerebral arteries with
      possible decreased regional cerebral blood flow by blocking sympathetic nerve
      mediated release of nitric oxide from the perivascular nitrergic nerves. This
      effect of Abeta can be prevented by endogenous oestrogen but not testosterone.

PMID- 21073662
TI  - Purinergic signalling in epithelial ion transport: regulation of secretion and
      absorption.
AB  - Intracellular ATP, the energy source for many reactions, is crucial for the
      activity of plasma membrane pumps and, thus, for the maintenance of transmembrane
      ion gradients. Nevertheless, ATP and other nucleotides/nucleosides are also
      extracellular molecules that regulate diverse cellular functions, including ion
      transport. In this review, I will first introduce the main components of the
      extracellular ATP signalling, which have become known as the purinergic
      signalling system. With more than 50 components or processes, just at cell
      membranes, it ranks as one of the most versatile signalling systems. This
      multitude of system components may enable differentiated regulation of diverse
      epithelial functions. As epithelia probably face the widest variety of potential
      ATP-releasing stimuli, a special attention will be given to stimuli and
      mechanisms of ATP release with a focus on exocytosis. Subsequently, I will
      consider membrane transport of major ions (Cl(-) , HCO(3)(-) , K(+) and Na(+) )
      and integrate possible regulatory functions of P2Y2, P2Y4, P2Y6, P2Y11, P2X4,
      P2X7 and adenosine receptors in some selected epithelia at the cellular level.
      Some purinergic receptors have noteworthy roles. For example, many studies to
      date indicate that the P2Y2 receptor is one common denominator in regulating ion
      channels on both the luminal and basolateral membranes of both secretory and
      absorptive epithelia. In exocrine glands though, P2X4 and P2X7 receptors act as
      cation channels and, possibly, as co-regulators of secretion. On an organ level,
      both receptor types can exert physiological functions and together with other
      partners in the purinergic signalling, integrated models for epithelial secretion
      and absorption are emerging.

PMID- 21073663
TI  - Effect of LKB1 deficiency on mitochondrial content, fibre type and muscle
      performance in the mouse diaphragm.
AB  - AIM: The liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signalling
      pathway is a major regulator of skeletal muscle metabolic processes. During
      exercise, LKB1-mediated phosphorylation of AMPK leads to its activation,
      promoting mitochondrial biogenesis and glucose transport, among other effects.
      The roles of LKB1 and AMPK have not been fully characterized in the diaphragm.
      METHODS: Two methods of AMPK activation were used to characterize LKB1/AMPK
      signalling in diaphragms from muscle-specific LKB1 knockout (KO) and littermate
      control mice: (1) acute injection of 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR) and (2) 5-min direct electrical stimulation of the
      diaphragm. Diaphragms were excised 60 min post-AICAR injection and immediately
      after electrical stimulation. RESULTS: AMPK phosphorylation increased with AICAR
      and electrical stimulation in control but not KO mice. Acetyl CoA carboxylase
      phosphorylation increased with AICAR in control but not KO mice, but increased in
      both genotypes with electrical stimulation. While the majority of mitochondrial
      protein levels were lower in KO diaphragms, uncoupling protein 3, complex I and
      cytochrome oxidase IV protein levels were not different between genotypes. KO
      diaphragms have a lower percentage of IIx fibres and an elevated percentage of
      IIb fibres when compared with control diaphragms. While in vitro peak force
      generation was similar between genotypes, KO diaphragms fatigued more quickly and
      had an impaired ability to recover. CONCLUSION: LKB1 regulates AMPK
      phosphorylation, mitochondrial protein expression, fibre type distribution, as
      well as recovery of the diaphragm from fatigue.

PMID- 21073664
TI  - Prediction and prevention of Type 1 diabetes mellitus.
AB  - Type 1A diabetes mellitus (T1DM) is caused by autoimmune islet beta-cell
      destruction with consequent severe insulin deficiency. We can now predict the
      development of T1DM by determining four biochemically characterized islet
      autoantibodies, namely those antibodies against insulin, glutamic acid
      decarboxylase 65, insulinoma antigen (IA)-2 (ICA512) and the zinc transporter
      ZnT8. We can also prevent T1DM in animal models, but the final goal is the
      prevention of T1DM in humans. Multiple clinical trials are underway investigating
      methods to prevent beta-cell destruction.

PMID- 21073665
TI  - Melanoma and DNA damage from a distance (farstander effect).

PMID- 21073666
TI  - Association of preoperative vitreous IL-8 and VEGF levels with visual acuity
      after vitrectomy in proliferative diabetic retinopathy.
AB  - PURPOSE: To determine whether the vitreous levels of interleukin 8 (IL-8) and
      vascular endothelial growth factor (VEGF) of patients with proliferative diabetic
      retinopathy (PDR) were associated with poor visual acuity after vitrectomy.
      METHODS: Observational cross-sectional study. Patient clinical characteristics
      and preoperative eye characteristics (63 eyes): visual acuity, iris
      neovascularization, vitreous haemorrhage, macular detachment, macular oedema,
      active retinal neovascularization, neovascularization of the disc, burned out PDR
      (defined as natural end stage of PDR with inactive membranes without previously
      performed laser photocoagulation) and panretinal photocoagulation were registered
      prior to vitrectomy for each patient. Vitreous VEGF and IL-8 levels were measured
      using the cytometric bead array method. Poor postoperative visual acuity was
      defined as visual acuity of <20/200 and was checked 2 years after vitrectomy.
      RESULTS: Twenty-one of the 63 eyes (33.3%) had poor visual acuity after
      vitrectomy. Univariate analysis showed that vitreous levels of IL-8, the absence
      of panretinal photocoagulation, preoperative macular detachment and poor
      preoperative visual acuity were significantly associated with poor final visual
      acuity after vitrectomy. A stepwise multiple logistic regression analysis showed
      that elevated vitreous levels of IL-8 (p < 0.0001), macular detachment (p =
      0.011) and the absence of panretinal photocoagulation (p = 0.03) were independent
      predictors for poor visual outcome. CONCLUSIONS: Elevated vitreous IL-8 level
      could either be a marker of ischaemic inflammatory reaction, or it could play a
      role in deteriorating visual acuity by DR progression or both. Further studies
      are needed to provide better understanding of IL-8 and inflammation involvement
      in visual prognosis in PDR.

PMID- 21073667
TI  - Poor responsiveness to antiplatelet drugs in acute coronary syndromes: clinical
      relevance and management.
AB  - Cardiovascular diseases are the most common cause of mortality and morbidity in
      Western countries, accounting for more than 40% of total mortality. An optimal
      pharmacological management in these patients is of major importance and
      antiplatelet agents remain the cornerstone of acute coronary syndrome (ACS)
      therapy at hospital admission and during percutaneous coronary interventions
      (PCI). The recently described poor biological responses to aspirin and
      clopidogrel have been source of major concern, especially in era of drug eluting
      stent implantation. Indeed, insufficient platelet inhibition at the time of PCI
      has been consistently associated with an increased risk of complications and
      recurrence of ischemic events. Despite the lack of uniformly accepted definitions
      of aspirin and clopidogrel poor response, we sought to describe the current
      evidence and gaps in knowledge. While trials on the potential benefit of an
      increased antiplatelet maintenance dose after PCI have shown only marginal
      benefits, the strengthening of the initial antiplatelet regimens by additional
      loading doses of clopidogrel, by the administration of glycoprotein IIb/IIIa
      receptor inhibitors or phosphodiesterase inhibitors might further improve
      outcomes during ACS and PCI in patients with poor responsiveness to conventional
      dual antiplatelet therapy. Overall, tailoring the antiplatelet treatment on the
      basis of the individual biological response improves the short-term outcome after
      PCI. New and more potent antiplatelet drugs may overcome the clinical
      consequences of the poor response to antiplatelet agents.

PMID- 21073668
TI  - COMT Val158Met-stress interaction in psychosis: role of background psychosis
      risk.
AB  - BACKGROUND: The interplay between the catechol-O-methyltransferase (COMT)
      Val158Met polymorphism and environmental stress may have etiological relevance
      for psychosis, but differential effects have been reported in healthy control and
      patient groups, suggesting that COMT Val158Met interactions with stress may be
      conditional on background genetic risk for psychotic disorder. METHODS: Patients
      with a nonaffective psychotic disorder (n = 86) and control participants (n =
      109) were studied with the experience sampling method (a structured diary
      technique) in order to assess stress, negative affect and momentary psychotic
      symptoms in the flow of daily life. RESULTS: Multilevel analyses revealed
      significant three-way interactions between group status (patient or control),
      COMT genotype and stress in the model of negative affect (chi(2)(2) = 13.26, P <
      0.01) as well as in the model of momentary psychotic symptoms (chi(2)(2) = 6.92,
      P < 0.05). Exploration of the three-way interaction revealed that in patients,
      COMT genotype moderated the association between stress and negative affect
      (chi(2)(4) = 11.50, P < 0.005), as well as the association between stress and
      momentary psychosis (chi(2)(4) = 12.79, P < 0.005). Met/Met genotype patients
      showed significantly increased psychotic and affective reactivity to stress in
      comparison to the Val/Met and Val/Val genotypes. In contrast, healthy controls
      did not display large or significant COMT Val158Met X stress interactions.
      CONCLUSIONS: Important differences exist in the effect of COMT Val158Met on
      stress reactivity, which may depend on background risk for psychotic disorder.
      Differential sensitivity to environmental stress occasioned by COMT Val158Met may
      be contingent on higher order interactions with genetic variation underlying
      psychotic disorder.

PMID- 21073669
TI  - Epidemiology of tornado destruction in rural northern Bangladesh: risk factors
      for death and injury.
AB  - The epidemiology of tornado-related disasters in the developing world is poorly
      understood. An August 2005 post-tornado cohort study in rural Bangladesh
      identified elevated levels of death and injury among the elderly (>= 60 years of
      age) (adjusted odds ratio (AOR) = 8.9 (95 per cent confidence interval (CI): 3.9
      20.2) and AOR = 1.6 (95 per cent CI: 1.4-1.8), respectively), as compared to 15
      24 year-olds, and among those outdoors versus indoors during the tornado (AOR =
      10.4 (95 per cent CI: 5.5-19.9) and AOR = 6.6 (95 per cent CI: 5.8-7.5),
      respectively). Females were 1.24 times (95 per cent CI: 1.15-1.33) more likely to
      be injured than males. Elevated risk of injury was significantly associated with
      structural damage to the house and tin construction materials. Seeking treatment
      was protective against death among the injured, odds ratio = 0.08 (95 per cent
      CI: 0.03-0.21). Further research is needed to develop injury prevention
      strategies and to address disparities in risk between age groups and between men
      and women.

PMID- 21073670
TI  - Exploring the feasibility of private micro flood insurance provision in
      Bangladesh.
AB  - This paper aims to contribute to the debate on the feasibility of the provision
      of micro flood insurance as an effective tool for spreading disaster risks in
      developing countries and examines the role of the institutional-organisational
      framework in assisting the design and implementation of such a micro flood
      insurance market. In Bangladesh, a private insurance market for property damage
      and livelihood risk due to natural disasters does not exist. Private insurance
      companies are reluctant to embark on an evidently unprofitable venture. Testing
      two different institutional-organisational models, this research reveals that the
      administration costs of micro-insurance play an important part in determining the
      long-term viability of micro flood insurance schemes. A government-facilitated
      process to overcome the differences observed in this study between the nonprofit
      micro-credit providers and profit-oriented private insurance companies is needed,
      building on the particular competence each party brings to the development of a
      viable micro flood insurance market through a public-private partnership.

PMID- 21073671
TI  - Synaptic changes in frontotemporal lobar degeneration: correlation with MAPT
      haplotype and APOE genotype.
AB  - AIMS: This immunohistochemical study quantified synaptic changes (synaptophysin
      and SNAP-25) in the frontal lobe of subjects with frontotemporal lobar
      degeneration (FTLD) and Alzheimer's disease (AD), and related these to APOE
      genotype and MAPT haplotype. METHODS: Frontal neocortex (BA9) of post mortem
      brains from subjects with FTLD (n = 20), AD (n = 10) and age-matched controls (n
      = 9) were studied immunohistochemically for synaptophysin and SNAP-25. RESULTS:
      We report that patients with FTLD have a significant increase in synaptophysin
      and depletion in SNAP-25 proteins compared to both control subjects and
      individuals with AD (P < 0.001). The FTLD up-regulation of synaptophysin is
      disease specific (P < 0.0001), and is not influenced by age (P = 0.787) or
      cortical atrophy (P = 0.248). The SNAP-25 depletion is influenced by a number of
      factors, including family history and histological characteristics of FTLD, APOE
      genotype, MAPT haplotype and gender. Thus, more profound loss of SNAP-25 occurred
      in tau-negative FTLD, and was associated with female gender and lack of family
      history of FTLD. Presence of APOEepsilon4 allele and MAPT H2 haplotype in FTLD
      had a significant influence on the expression of synaptic proteins, specifically
      invoking a decrease in SNAP-25. CONCLUSIONS: Our results suggest that synaptic
      expression in FTLD is influenced by a number of genetic factors which need to be
      taken into account in future neuropathological and biochemical studies dealing
      with altered neuronal mechanisms of the disease. The selective loss of SNAP-25 in
      FTLD may be closely related to the core clinical non-cognitive features of the
      disease.

PMID- 21073672
TI  - Mother Nature versus human nature: public compliance with evacuation and
      quarantine.
AB  - Effectively controlling the spread of contagious illnesses has become a critical
      focus of disaster planning. It is likely that quarantine will be a key part of
      the overall public health strategy utilised during a pandemic, an act of
      bioterrorism or other emergencies involving contagious agents. While the United
      States lacks recent experience of large-scale quarantines, it has considerable
      accumulated experience of large-scale evacuations. Risk perception, life
      circumstance, work-related issues, and the opinions of influential family,
      friends and credible public spokespersons all play a role in determining
      compliance with an evacuation order. Although the comparison is not reported
      elsewhere to our knowledge, this review of the principal factors affecting
      compliance with evacuations demonstrates many similarities with those likely to
      occur during a quarantine. Accurate identification and understanding of barriers
      to compliance allows for improved planning to protect the public more
      effectively.

PMID- 21073673
TI  - Long-term outcomes of obscure gastrointestinal bleeding after CT enterography:
      does negative CT enterography predict lower long-term rebleeding rate?
AB  - BACKGROUND AND AIM: Computed tomography enterography (CTE) is a promising
      modality for small bowel imaging. However, the role of CTE in the evaluation of
      obscure gastrointestinal bleeding (OGIB) has not been established. We
      investigated the efficacy of CTE in diagnosing OGIB and the long-term outcomes
      based on CTE findings, with special reference to negative CTE. METHODS: A total
      of 63 consecutive patients who had undergone CTE for OGIB were enrolled, and
      their pre- and post-CTE clinical data were collected. "Specific treatments" were
      defined as treatments directly aimed at resolving presumed bleeding causes,
      including hemostasis and operation, while "non-specific treatments" were defined
      as symptomatic treatments for anemia. RESULTS: Among 60 patients for whom long
      term follow-up data were available, positive lesions were found in 16 patients
      (26.7%). The overall rebleeding rate was 21.7% during a mean follow up of 17.6 +/
      4.7 months. There was no significant difference in the cumulative rebleeding
      rates between patients with positive and negative CTE results (P = 0.241). All
      patients who received specific treatments after CTE did not rebleed (0/8). In
      positive CTE patients, specific treatments significantly reduced the rebleeding
      rate (P = 0.023). CONCLUSIONS: CTE has a high rate of detecting overt OGIB.
      However, negative CTE results do not predict lower long-term rebleeding, and such
      patients with OGIB should be closely observed. In patients with positive CTE,
      more vigorous management significantly reduces the incidence of rebleeding.

PMID- 21073674
TI  - Treatment of autoimmune hepatitis: a review of current and evolving therapies.
AB  - Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of
      the liver. Presentation can vary from the asymptomatic individual with abnormal
      liver function test to fulminant liver failure. The diagnosis is based on the
      combination of biochemical, autoimmune, and histological parameters, and
      exclusion of other liver diseases. Standard therapy consists of a combination of
      corticosteroids and azathioprine, which is efficacious in 80% of patients.
      Alternative therapies are increasingly being explored in patients who do not
      respond to the standard treatment and/or have unacceptable adverse effects. This
      review examines the role of alternative drugs (second-line agents) available for
      AIH treatment non-responders. These agents include budesonide, mycophenolate
      mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab,
      ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of
      opportunistic infections and malignancies are discussed. A treatment algorithm is
      proposed for the management of patients with AIH treatment non-responders.

PMID- 21073675
TI  - Duodenal chemosensing: master control for epigastric sensation?

PMID- 21073676
TI  - Transcriptomic response of red grouse to gastro-intestinal nematode parasites and
      testosterone: implications for population dynamics.
AB  - A central issue in ecology is in understanding the relative influences of
      intrinsic and extrinsic effects on population regulation. Previous studies on the
      cyclic population dynamics of red grouse (Lagopus lagopus scoticus) have
      emphasized the destabilizing effects of either nematode parasites or territorial
      behaviour and aggression. The potential interacting effects of these processes,
      mediated through density-dependent, environmentally induced alterations of host
      immunocompetence influencing susceptibility to parasites have not been
      considered. Male red grouse at high density are more aggressive, associated with
      increased testosterone, which potentially could lead to reduced immunocompetence
      at a stage when parasites are most prevalent. This could depress individual
      condition, breeding performance and survival and thus drive or contribute to
      overall reductions in population size. Here, we characterize the transcriptomic
      response of grouse to nematode parasite infection and investigate how this is
      subsequently affected by testosterone, using a microarray approach contrasting
      red grouse with high and low parasite load at both high and low testosterone
      titre. A suite of 52 transcripts showed a significant level of up-regulation to
      either chronic parasite load or experimental parasite infection. Of these, 51
      (98%) showed a reduced level of expression under conditions of high parasite load
      and high testosterone. The genes up-regulated by parasites and then down
      regulated at high testosterone titre were not necessarily associated with immune
      response, as might be intuitively expected. The results are discussed in relation
      to the fitness and condition of individual red grouse and factors influencing the
      regulation of abundance in natural populations.

PMID- 21073677
TI  - Molecular epidemiology of malaria prevalence and parasitaemia in a wild bird
      population.
AB  - Avian malaria (Plasmodium spp.) and other blood parasitic infections of birds
      constitute increasingly popular model systems in ecological and evolutionary host
      parasite studies. Field studies of these parasites commonly use two traits in
      hypothesis testing: infection status (or prevalence at the population level) and
      parasitaemia, yet the causes of variation in these traits remain poorly
      understood. Here, we use quantitative PCR to investigate fine-scale environmental
      and host predictors of malaria infection status and parasitaemia in a large 4
      year data set from a well-characterized population of blue tits (Cyanistes
      caeruleus). We also examine the temporal dynamics of both traits within
      individuals. Both infection status and parasitaemia showed marked temporal and
      spatial variation within this population. However, spatiotemporal patterns of
      prevalence and parasitaemia were non-parallel, suggesting that different
      biological processes underpin variation in these two traits at this scale.
      Infection probability and parasitaemia both increased with host age, and
      parasitaemia was higher in individuals investing more in reproduction (those with
      larger clutch sizes). Several local environmental characteristics predicted
      parasitaemia, including food availability, altitude, and distance from the
      woodland edge. Although infection status and parasitaemia were somewhat
      repeatable within individuals, infections were clearly dynamic: patent infections
      frequently disappeared from the bloodstream, with up to 26% being lost between
      years, and parasitaemia also fluctuated within individuals across years in a
      pattern that mirrored annual population-level changes. Overall, these findings
      highlight the ecological complexity of avian malaria infections in natural
      populations, while providing valuable insight into the fundamental biology of
      this system that will increase its utility as a model host-parasite system.

PMID- 21073678
TI  - Update on uncommon pleural effusions.
AB  - Although infections, malignancies and heart failure are responsible for the
      majority of pleural effusions, there are many other causes and several uncommon
      but distinctive types of pleural fluid. For this update we have chosen several
      uncommon forms of pleural effusions or disorders in which there have been recent
      advances in our understanding over the past several years. Chylothorax,
      pseudochylothorax and urinothorax are associated with characteristic clinical
      contexts and pleural fluid parameters but are likely underdiagnosed. Yellow nail
      syndrome is a rare disorder that can be associated with chylothorax and manifests
      multisystem features. Recognition of these entities is important because each of
      these disorders is associated with distinctive aetiology and management
      modalities. Correct diagnosis depends on the clinician's awareness of the
      clinical contexts and manifestations along with diagnostic pleural fluid findings
      in these disorders.

PMID- 21073679
TI  - Wound care requires a refocusing of effort--should 2011 be the time?

PMID- 21073682
TI  - Nurses' use of water-filled gloves in preventing heel pressure ulcer in the
      University College Hospital, Ibadan, Nigeria.
AB  - This cross-sectional descriptive survey examined use (knowledge, perception and
      practices) of water-filled gloves (WFGs) by nurses in the prevention of heel
      pressure ulcer (PU) in the University College Hospital (UCH), Ibadan, Nigeria.
      Participants were 250 purposively selected nurses working in the Neurosciences
      and Surgical units. Quantitative data were generated through the administration
      of a semi-structured questionnaire, whereas the qualitative data were collected
      through in-depth interview. Hypotheses were tested using chi-square analysis at a
      significance level of 0.05, whereas the manual content analysis was used to
      analyse the qualitative data. Results showed that a significant number of nurses
      at UCH, Ibadan, were knowledgeable about WFGs and actually used them in their
      clinical practice. Years of experience in clinical practice was found to be
      significantly related to knowledge and use of WFGs in heel PU (X(2) = 41.677; DF
      = 5; P = 0.001). Nurses with adequate knowledge of risk factors in the
      development of PU used WFGs more than those who were not aware (X(2) = 44.907; DF
      = 3; P = 0.009). Nurses' perception about WFGs was also significantly related to
      its use (X(2) = 4.527; DF = 1; P = 0.033). Although knowledge level and
      perception of WFGs and its use by nurses was fairly adequate, continuous
      education for practicing nurses should be encouraged in resource-limited
      settings.

PMID- 21073683
TI  - Post-surgical wound infections involving Enterobacteriaceae with reduced
      susceptibility to beta-lactams in two Portuguese hospitals.
AB  - The post-surgical period is often critical for infection acquisition. The
      combination of patient injury and environmental exposure through breached skin
      add risk to pre-existing conditions such as drug or depressed immunity. Several
      factors such as the period of hospital staying after surgery, base disease, age,
      immune system condition, hygiene policies, careless prophylactic drug
      administration and physical conditions of the healthcare centre may contribute to
      the acquisition of a nosocomial infection. A purulent wound can become
      complicated whenever antimicrobial therapy becomes compromised. In this pilot
      study, we analysed Enterobacteriaceae strains, the most significant gram-negative
      rods that may occur in post-surgical skin and soft tissue infections (SSTI)
      presenting reduced beta-lactam susceptibility and those presenting extended
      spectrum beta-lactamases (ESBL). There is little information in our country
      regarding the relationship between beta-lactam susceptibility, ESBL and
      development of resistant strains of microorganisms in SSTI. Our main results
      indicate Escherichia coli and Klebsiella spp. are among the most frequent
      enterobacteria (46% and 30% respectively) with ESBL production in 72% of
      Enterobacteriaceae isolates from SSTI. Moreover, coinfection occurred
      extensively, mainly with Pseudomonas aeruginosa and Methicillin-resistant
      Staphylococcus aureus (18% and 13%, respectively). These results suggest future
      research to explore if and how these associations are involved in the development
      of antibiotic resistance.

PMID- 21073684
TI  - The role of mast cells in the early stages of wound healing.

PMID- 21073685
TI  - Nicorandil-induced peristomal ulceration.

PMID- 21073686
TI  - Treatment of chronic wounds: time for immunologic concern on drug design?

PMID- 21073687
TI  - Silver dressings.

PMID- 21073689
TI  - Rapid identification and typing of Yersinia pestis and other Yersinia species by
      matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry.
AB  - BACKGROUND: Accurate identification is necessary to discriminate harmless
      environmental Yersinia species from the food-borne pathogens Yersinia
      enterocolitica and Yersinia pseudotuberculosis and from the group A bioterrorism
      plague agent Yersinia pestis. In order to circumvent the limitations of current
      phenotypic and PCR-based identification methods, we aimed to assess the
      usefulness of matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) protein profiling for accurate and rapid identification of Yersinia species.
      As a first step, we built a database of 39 different Yersinia strains
      representing 12 different Yersinia species, including 13 Y. pestis isolates
      representative of the Antiqua, Medievalis and Orientalis biotypes. The organisms
      were deposited on the MALDI-TOF plate after appropriate ethanol-based
      inactivation, and a protein profile was obtained within 6 minutes for each of the
      Yersinia species. RESULTS: When compared with a 3,025-profile database, every
      Yersinia species yielded a unique protein profile and was unambiguously
      identified. In the second step of analysis, environmental and clinical isolates
      of Y. pestis (n = 2) and Y. enterocolitica (n = 11) were compared to the database
      and correctly identified. In particular, Y. pestis was unambiguously identified
      at the species level, and MALDI-TOF was able to successfully differentiate the
      three biotypes. CONCLUSION: These data indicate that MALDI-TOF can be used as a
      rapid and accurate first-line method for the identification of Yersinia isolates.

PMID- 21073690
TI  - Towards resolving Lamiales relationships: insights from rapidly evolving
      chloroplast sequences.
AB  - BACKGROUND: In the large angiosperm order Lamiales, a diverse array of highly
      specialized life strategies such as carnivory, parasitism, epiphytism, and
      desiccation tolerance occur, and some lineages possess drastically accelerated
      DNA substitutional rates or miniaturized genomes. However, understanding the
      evolution of these phenomena in the order, and clarifying borders of and
      relationships among lamialean families, has been hindered by largely unresolved
      trees in the past. RESULTS: Our analysis of the rapidly evolving trnK/matK, trnL
      F and rps16 chloroplast regions enabled us to infer more precise phylogenetic
      hypotheses for the Lamiales. Relationships among the nine first-branching
      families in the Lamiales tree are now resolved with very strong support.
      Subsequent to Plocospermataceae, a clade consisting of Carlemanniaceae plus
      Oleaceae branches, followed by Tetrachondraceae and a newly inferred clade
      composed of Gesneriaceae plus Calceolariaceae, which is also supported by
      morphological characters. Plantaginaceae (incl. Gratioleae) and Scrophulariaceae
      are well separated in the backbone grade; Lamiaceae and Verbenaceae appear in
      distant clades, while the recently described Linderniaceae are confirmed to be
      monophyletic and in an isolated position. CONCLUSIONS: Confidence about deep
      nodes of the Lamiales tree is an important step towards understanding the
      evolutionary diversification of a major clade of flowering plants. The degree of
      resolution obtained here now provides a first opportunity to discuss the
      evolution of morphological and biochemical traits in Lamiales. The multiple
      independent evolution of the carnivorous syndrome, once in Lentibulariaceae and a
      second time in Byblidaceae, is strongly supported by all analyses and topological
      tests. The evolution of selected morphological characters such as flower symmetry
      is discussed. The addition of further sequence data from introns and spacers
      holds promise to eventually obtain a fully resolved plastid tree of Lamiales.

PMID- 21073691
TI  - Compassionate use of interventions: results of a European Clinical Research
      Infrastructures Network (ECRIN) survey of ten European countries.
AB  - BACKGROUND: 'Compassionate use' programmes allow medicinal products that are not
      authorised, but are in the development process, to be made available to patients
      with a severe disease who have no other satisfactory treatment available to them.
      We sought to understand how such programmes are regulated in ten European Union
      countries. METHODS: The European Clinical Research Infrastructures Network
      (ECRIN) conducted a comprehensive survey on clinical research regulatory
      requirements, including questions on regulations of 'compassionate use'
      programmes. Ten European countries, covering approximately 70% of the EU
      population, were included in the survey (Austria, Denmark, France, Germany,
      Hungary, Ireland, Italy, Spain, Sweden, and the UK). RESULTS: European Regulation
      726/2004/EC is clear on the intentions of 'compassionate use' programmes and
      aimed to harmonise them in the European Union. The survey reveals that different
      countries have adopted different requirements and that 'compassionate use' is not
      interpreted in the same way across Europe. Four of the ten countries surveyed
      have no formal regulatory system for the programmes. We discuss the need for
      'compassionate use' programmes and their regulation where protection of patients
      is paramount. CONCLUSIONS: 'Compassionate use' is a misleading term and should be
      replaced with 'expanded access'. There is a need for expanded access programmes
      in order to serve the interests of seriously ill patients who have no other
      treatment options. To protect these patients, European legislation needs to be
      more explicit and informative with regard to the regulatory requirements,
      restrictions, and responsibilities in expanded access programmes.

PMID- 21073692
TI  - In vitro gene regulatory networks predict in vivo function of liver.
AB  - BACKGROUND: Evolution of toxicity testing is predicated upon using in vitro cell
      based systems to rapidly screen and predict how a chemical might cause toxicity
      to an organ in vivo. However, the degree to which we can extend in vitro results
      to in vivo activity and possible mechanisms of action remains to be fully
      addressed. RESULTS: Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as
      a model chemical to compare and determine how we might extrapolate from in vitro
      data to in vivo effects. We found 341 transcripts differentially expressed in
      common among in vitro and in vivo assays in response to TNT. The major functional
      term corresponding to these transcripts was cell cycle. Similarly modulated
      common pathways were identified between in vitro and in vivo. Furthermore, we
      uncovered the conserved common transcriptional gene regulatory networks between
      in vitro and in vivo cellular liver systems that responded to TNT exposure, which
      mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks.
      Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and
      downregulated by TNT both in vitro and in vivo. CONCLUSIONS: The results of our
      investigation of TNT effects on gene expression in liver suggest that gene
      regulatory networks obtained from an in vitro system can predict in vivo function
      and mechanisms. Inhibiting PTTG1 and its targeted cell cycle related genes could
      be key mechanism for TNT induced liver toxicity.

PMID- 21073693
TI  - Effect of adaptive abilities on utilities, direct or mediated by mental health?
AB  - BACKGROUND: In cost-utility analyses gain in health can be measured using health
      state utilities. Health state utilities can be elicited from members of the
      public or from patients. Utilities given by patients tend to be higher than
      utilities given by members of the public. This difference is often suggested to
      be explained by adaptation, but this has not yet been investigated in patients.
      Here, we investigate if, besides health related quality of life (HRQL), persons'
      ability to adapt can explain health state utilities. Both the direct effect of
      persons' adaptive abilities on health state utilities and the indirect effect,
      where HRQL mediates the effect of ability to adapt, are examined. METHODS: In
      total 125 patients with Rheumatoid Arthritis were interviewed. Participants gave
      valuations of their own health on a visual analogue scale (VAS) and time trade
      off (TTO). To estimate persons' ability to adapt, patients filled in
      questionnaires measuring Self-esteem, Mastery, and Optimism. Finally they
      completed the SF-36 measuring HRQL. Regression analyses were used to investigate
      the direct and mediated effect of ability to adapt on health state utilities.
      RESULTS: Persons' ability to adapt did not add considerably to the explanation of
      health state utilities above HRQL. In the TTO no additional variance was
      explained by adaptive abilities (Delta R2 = .00, beta = .02), in the VAS a minor
      proportion of the variance was explained by adaptive abilities (Delta R2 = .05,
      beta = .33). The effect of adaptation on health state utilities seems to be
      mediated by the mental health domain of quality of life. CONCLUSIONS: Patients
      with stronger adaptive abilities, based on their optimism, mastery and self
      esteem, may more easily enhance their mental health after being diagnosed with a
      chronic illness, which leads to higher health state utilities.

PMID- 21073694
TI  - Patterns of human gene expression variance show strong associations with
      signaling network hierarchy.
AB  - BACKGROUND: Understanding organizational principles of cellular networks is one
      of the central goals of systems biology. Although much has been learnt about gene
      expression programs under specific conditions, global patterns of expressional
      variation (EV) of genes and their relationship to cellular functions and
      physiological responses is poorly understood. RESULTS: To understand global
      principles of relationship between transcriptional regulation of human genes and
      their functions, we have leveraged large-scale datasets of human gene expression
      measurements across a wide spectrum of cell conditions. We report that human
      genes are highly diverse in terms of their EV; while some genes have highly
      variable expression pattern, some seem to be relatively ubiquitously expressed
      across a wide range of conditions. The wide spectrum of gene EV strongly
      correlates with the positioning of proteins within the signaling network
      hierarchy, such that, secreted extracellular receptor ligands and membrane
      receptors have the highest EV, and intracellular signaling proteins have the
      lowest EV in the genome. Our analysis shows that this pattern of EV reflects
      functional centrality: proteins with highly specific signaling functions are
      modulated more frequently than those with highly central functions in the
      network, which is also consistent with previous studies on tissue-specific gene
      expression. Interestingly, these patterns of EV along the signaling network
      hierarchy have significant correlations with promoter architectures of respective
      genes. CONCLUSION: Our analyses suggest a generic systems level mechanism of
      regulation of the cellular signaling network at the transcriptional level.

PMID- 21073695
TI  - The Vitis vinifera sugar transporter gene family: phylogenetic overview and
      macroarray expression profiling.
AB  - BACKGROUND: In higher plants, sugars are not only nutrients but also important
      signal molecules. They are distributed through the plant via sugar transporters,
      which are involved not only in sugar long-distance transport via the loading and
      the unloading of the conducting complex, but also in sugar allocation into source
      and sink cells. The availability of the recently released grapevine genome
      sequence offers the opportunity to identify sucrose and monosaccharide
      transporter gene families in a woody species and to compare them with those of
      the herbaceous Arabidopsis thaliana using a phylogenetic analysis. RESULTS: In
      grapevine, one of the most economically important fruit crop in the world, it
      appeared that sucrose and monosaccharide transporter genes are present in 4 and
      59 loci, respectively and that the monosaccharide transporter family can be
      divided into 7 subfamilies. Phylogenetic analysis of protein sequences has
      indicated that orthologs exist between Vitis and Arabidospis. A search for cis
      regulatory elements in the promoter sequences of the most characterized
      transporter gene families (sucrose, hexoses and polyols transporters), has
      revealed that some of them might probably be regulated by sugars. To profile
      several genes simultaneously, we created a macroarray bearing cDNA fragments
      specific to 20 sugar transporter genes. This macroarray analysis has revealed
      that two hexose (VvHT1, VvHT3), one polyol (VvPMT5) and one sucrose (VvSUC27)
      transporter genes, are highly expressed in most vegetative organs. The expression
      of one hexose transporter (VvHT2) and two tonoplastic monosaccharide transporter
      (VvTMT1, VvTMT2) genes are regulated during berry development. Finally, three
      putative hexose transporter genes show a preferential organ specificity being
      highly expressed in seeds (VvHT3, VvHT5), in roots (VvHT2) or in mature leaves
      (VvHT5). CONCLUSIONS: This study provides an exhaustive survey of sugar
      transporter genes in Vitis vinifera and revealed that sugar transporter gene
      families in this woody plant are strongly comparable to those of herbaceous
      species. Dedicated macroarrays have provided a Vitis sugar transporter genes
      expression profiling, which will likely contribute to understand their
      physiological functions in plant and berry development. The present results might
      also have a significant impact on our knowledge on plant sugar transporters.

PMID- 21073696
TI  - Three non-autonomous signals collaborate for nuclear targeting of CrMYC2, a
      Catharanthus roseus bHLH transcription factor.
AB  - BACKGROUND: CrMYC2 is an early jasmonate-responsive bHLH transcription factor
      involved in the regulation of the expression of the genes of the terpenic indole
      alkaloid biosynthesis pathway in Catharanthus roseus. In this paper, we
      identified the amino acid domains necessary for the nuclear targeting of CrMYC2.
      FINDINGS: We examined the intracellular localization of whole CrMYC2 and of
      various deletion mutants, all fused with GFP, using a transient expression assay
      in onion epidermal cells. Sequence analysis of this protein revealed the presence
      of four putative basic nuclear localization signals (NLS). Assays showed that
      none of the predicted NLS is active alone. Further functional dissection of
      CrMYC2 showed that the nuclear targeting of this transcription factor involves
      the cooperation of three domains located in the C-terminal region of the protein.
      The first two domains are located at amino acid residues 454-510 and 510-562 and
      contain basic classical monopartite NLSs; these regions are referred to as NLS3
      (KRPRKR) and NLS4 (EAERQRREK), respectively. The third domain, between residues
      617 and 652, is rich in basic amino acids that are well conserved in other
      phylogenetically related bHLH transcription factors. Our data revealed that these
      three domains are inactive when isolated but act cooperatively to target CrMYC2
      to the nucleus. CONCLUSIONS: This study identified three amino acid domains that
      act in cooperation to target the CrMYC2 transcription factor to the nucleus.
      Further fine structure/function analysis of these amino acid domains will allow
      the identification of new NLS domains and will allow the investigation of the
      related molecular mechanisms involved in the nuclear targeting of the CrMYC2 bHLH
      transcription factor.

PMID- 21073697
TI  - Measurement properties of the benign prostatic hyperplasia impact index in
      tadalafil studies.
AB  - BACKGROUND: To assess the measurement properties of the Benign Prostatic
      Hyperplasia Impact Index (BII) for use in men with Lower Urinary Tract Symptoms
      (LUTS) secondary to Benign Prostatic Hyperplasia (BPH) treated with tadalafil.
      METHODS: Data from a dose-titration (Study 1) and a dose-finding placebo
      controlled (Study 2) tadalafil studies of men 45 years of age or older with
      moderate to severe LUTS (N = 281; N = 1053) were included in this post-hoc
      analysis. Measures included the BII, International Prostate Symptom Score (IPSS),
      IPSS Quality of Life Index (IPSS-QoL), LUTS Global Assessment Question,
      uroflowmetry measure peak flow rate (Qmax) and postvoid residual volume (PVR).
      Spearman rank and Pearson correlation coefficients were computed between the BII
      score and the other measures at each visit. Wilcoxin two-sample tests, t-tests
      and general linear modeling compared BII scores of subjects with global ratings
      of improvement versus no improvement, and subjects taking tadalafil versus
      placebo. Effect size, standardized response mean and Guyatt's responsiveness
      statistic were calculated for BII and IPSS change scores. RESULTS: There were
      high correlations between BII and IPSS & IPSS-QoL and low correlations between
      BII and Qmax & PVR at each visit. There were significant differences in BII at
      the End-of-Study Visit between subjects reporting improvement versus subjects
      reporting no improvement (Studies 1 and 2, P < .0001) and subjects taking
      tadalafil versus subjects taking placebo (Study 1, P = .0045; Study 2, P =
      .0064). The BII and IPSS were both responsive to change. CONCLUSIONS: Results
      show that the BII is reliable, shows responsiveness to change in patients with
      BPH-LUTS, and demonstrates construct validity.

PMID- 21073698
TI  - Prevalence of genetic differences in phosphorylcholine expression between
      nontypeable Haemophilus influenzae and Haemophilus haemolyticus.
AB  - BACKGROUND: Although non-typeable (NT) Haemophilus influenzae and Haemophilus
      haemolyticus are closely related human commensals, H. haemolyticus is non
      pathogenic while NT H. influenzae is an important cause of respiratory tract
      infections. Phase-variable phosphorylcholine (ChoP) modification of
      lipooligosaccharide (LOS) is a NT H. influenzae virulence factor that,
      paradoxically, may also promote complement activation by binding C-reactive
      protein (CRP). CRP is known to bind more to ChoP positioned distally than
      proximally in LOS, and the position of ChoP within LOS is dictated by specific
      licD alleles (designated here as licDI, licDIII, and licDIV) that are present in
      a lic1 locus. The lic1 locus contains the licA-licD genes, and ChoP-host
      interactions may also be influenced by a second lic1 locus that allows for dual
      ChoP substitutions in the same strain, or by the number of licA gene
      tetranucleotide repeats (5'-CAAT-3') that reflect phase-variation mutation rates.
      RESULTS: Using dot-blot hybridization, 92% of 88 NT H. influenzae and 42.6% of
      109 H. haemolyticus strains possessed a lic1 locus. Eight percent of NT H.
      influenzae and none of the H. haemolyticus strains possessed dual copies of lic1.
      The licDIII and licDIV gene alleles were distributed similarly (18-22%) among the
      NT H. influenzae and H. haemolyticus strains while licDI alleles were present in
      45.5% of NT H. influenzae but in less than 1% of H. haemolyticus strains (P <
      .0001). NT H. influenzae had an average of 26.8 tetranucleotide repeats in licA
      compared to 14.8 repeats in H. haemolyticus (P < .05). In addition, NT H.
      influenzae strains that possessed a licDIII allele had increased numbers of
      repeats compared to NT H. influenzae with other licD alleles (P < .05).
      CONCLUSIONS: These data demonstrate that genetic similarities and differences of
      ChoP expression exist between NT H. influenzae and H. haemolyticus and strengthen
      the hypothesis that, at the population level, these differences may, in part,
      provide an advantage in the virulence of NT H. influenzae.

PMID- 21073699
TI  - Impact of the Staphylococcus epidermidis LytSR two-component regulatory system on
      murein hydrolase activity, pyruvate utilization and global transcriptional
      profile.
AB  - BACKGROUND: Staphylococcus epidermidis has emerged as one of the most important
      nosocomial pathogens, mainly because of its ability to colonize implanted
      biomaterials by forming a biofilm. Extensive studies are focused on the molecular
      mechanisms involved in biofilm formation. The LytSR two-component regulatory
      system regulates autolysis and biofilm formation in Staphylococcus aureus.
      However, the role of LytSR played in S. epidermidis remained unknown. RESULTS: In
      the present study, we demonstrated that lytSR knock-out in S. epidermidis did not
      alter susceptibility to Triton X-100 induced autolysis. Quantitative murein
      hydrolase assay indicated that disruption of lytSR in S. epidermidis resulted in
      decreased activities of extracellular murein hydrolases, although zymogram showed
      no apparent differences in murein hydrolase patterns between S. epidermidis
      strain 1457 and its lytSR mutant. Compared to the wild-type counterpart,
      1457DeltalytSR produced slightly more biofilm, with significantly decreased dead
      cells inside. Microarray analysis showed that lytSR mutation affected the
      transcription of 164 genes (123 genes were upregulated and 41 genes were
      downregulated). Specifically, genes encoding proteins responsible for protein
      synthesis, energy metabolism were downregulated, while genes involved in amino
      acid and nucleotide biosynthesis, amino acid transporters were upregulated.
      Impaired ability to utilize pyruvate and reduced activity of arginine deiminase
      was observed in 1457DeltalytSR, which is consistent with the microarray data.
      CONCLUSIONS: The preliminary results suggest that in S. epidermidis LytSR two
      component system regulates extracellular murein hydrolase activity, bacterial
      cell death and pyruvate utilization. Based on the microarray data, it appears
      that lytSR inactivation induces a stringent response. In addition, LytSR may
      indirectly enhance biofilm formation by altering the metabolic status of the
      bacteria.

PMID- 21073701
TI  - Structural constraints revealed in consistent nucleosome positions in the genome
      of S. cerevisiae.
AB  - BACKGROUND: Recent advances in the field of high-throughput genomics have
      rendered possible the performance of genome-scale studies to define the
      nucleosomal landscapes of eukaryote genomes. Such analyses are aimed towards
      providing a better understanding of the process of nucleosome positioning, for
      which several models have been suggested. Nevertheless, questions regarding the
      sequence constraints of nucleosomal DNA and how they may have been shaped through
      evolution remain open. In this paper, we analyze in detail different experimental
      nucleosome datasets with the aim of providing a hypothesis for the emergence of
      nucleosome-forming sequences. RESULTS: We compared the complete sets of
      nucleosome positions for the budding yeast (Saccharomyces cerevisiae) as defined
      in the output of two independent experiments with the use of two different
      experimental techniques. We found that < 10% of the experimentally defined
      nucleosome positions were consistently positioned in both datasets. This subset
      of well-positioned nucleosomes, when compared with the bulk, was shown to have
      particular properties at both sequence and structural levels. Consistently
      positioned nucleosomes were also shown to occur preferentially in pairs of
      dinucleosomes, and to be surprisingly less conserved compared with their adjacent
      nucleosome-free linkers. CONCLUSION: Our findings may be combined into a
      hypothesis for the emergence of a weak nucleosome-positioning code. According to
      this hypothesis, consistent nucleosomes may be partly guided by nearby nucleosome
      free regions through statistical positioning. Once established, a set of well
      positioned consistent nucleosomes may impose secondary constraints that further
      shape the structure of the underlying DNA. We were able to capture these
      constraints through the application of a recently introduced structural property
      that is related to the symmetry of DNA curvature. Furthermore, we found that both
      consistently positioned nucleosomes and their adjacent nucleosome-free regions
      show an increased tendency towards conservation of this structural feature.

PMID- 21073700
TI  - Comparative transcriptomics of drought responses in Populus: a meta-analysis of
      genome-wide expression profiling in mature leaves and root apices across two
      genotypes.
AB  - BACKGROUND: Comparative genomics has emerged as a promising means of unravelling
      the molecular networks underlying complex traits such as drought tolerance. Here
      we assess the genotype-dependent component of the drought-induced transcriptome
      response in two poplar genotypes differing in drought tolerance. Drought-induced
      responses were analysed in leaves and root apices and were compared with
      available transcriptome data from other Populus species. RESULTS: Using a multi
      species designed microarray, a genomic DNA-based selection of probesets provided
      an unambiguous between-genotype comparison. Analyses of functional group
      enrichment enabled the extraction of processes physiologically relevant to
      drought response. The drought-driven changes in gene expression occurring in root
      apices were consistent across treatments and genotypes. For mature leaves, the
      transcriptome response varied weakly but in accordance with the duration of water
      deficit. A differential clustering algorithm revealed similar and divergent gene
      co-expression patterns among the two genotypes. Since moderate stress levels
      induced similar physiological responses in both genotypes, the genotype-dependent
      transcriptional responses could be considered as intrinsic divergences in genome
      functioning. Our meta-analysis detected several candidate genes and processes
      that are differentially regulated in root and leaf, potentially under
      developmental control, and preferentially involved in early and long-term
      responses to drought. CONCLUSIONS: In poplar, the well-known drought-induced
      activation of sensing and signalling cascades was specific to the early response
      in leaves but was found to be general in root apices. Comparing our results to
      what is known in arabidopsis, we found that transcriptional remodelling included
      signalling and a response to energy deficit in roots in parallel with
      transcriptional indices of hampered assimilation in leaves, particularly in the
      drought-sensitive poplar genotype.

PMID- 21073702
TI  - Assessment and optimisation of normalisation methods for dual-colour antibody
      microarrays.
AB  - BACKGROUND: Recent advances in antibody microarray technology have made it
      possible to measure the expression of hundreds of proteins simultaneously in a
      competitive dual-colour approach similar to dual-colour gene expression
      microarrays. Thus, the established normalisation methods for gene expression
      microarrays, e.g. loess regression, can in principle be applied to protein
      microarrays. However, the typical assumptions of such normalisation methods might
      be violated due to a bias in the selection of the proteins to be measured. Due to
      high costs and limited availability of high quality antibodies, the current
      arrays usually focus on a high proportion of regulated targets. Housekeeping
      features could be used to circumvent this problem, but they are typically
      underrepresented on protein arrays. Therefore, it might be beneficial to select
      invariant features among the features already represented on available arrays for
      normalisation by a dedicated selection algorithm. RESULTS: We compare the
      performance of several normalisation methods that have been established for dual
      colour gene expression microarrays. The focus is on an invariant selection
      algorithm, for which effective improvements are proposed. In a simulation study
      the performances of the different normalisation methods are compared with respect
      to their impact on the ability to correctly detect differentially expressed
      features. Furthermore, we apply the different normalisation methods to a
      pancreatic cancer data set to assess the impact on the classification power.
      CONCLUSIONS: The simulation study and the data application demonstrate the
      superior performance of the improved invariant selection algorithms in comparison
      to other normalisation methods, especially in situations where the assumptions of
      the usual global loess normalisation are violated.

PMID- 21073703
TI  - A study protocol of a randomised controlled trial incorporating a health economic
      analysis to investigate if additional allied health services for rehabilitation
      reduce length of stay without compromising patient outcomes.
AB  - BACKGROUND: Reducing patient length of stay is a high priority for health service
      providers. Preliminary information suggests additional Saturday rehabilitation
      services could reduce the time a patient stays in hospital by three days. This
      large trial will examine if providing additional physiotherapy and occupational
      therapy services on a Saturday reduces health care costs, and improves the health
      of hospital inpatients receiving rehabilitation compared to the usual Monday to
      Friday service. We will also investigate the cost effectiveness and patient
      outcomes of such a service. METHODS/DESIGN: A randomised controlled trial will
      evaluate the effect of providing additional physiotherapy and occupational
      therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient
      rehabilitation at two metropolitan sites will be randomly allocated to the
      intervention group or control group. The control group will receive usual care
      physiotherapy and occupational therapy from Monday to Friday while the
      intervention group will receive the same amount of rehabilitation as the control
      group Monday to Friday plus a full physiotherapy and occupational therapy service
      on Saturday. The primary outcomes will be patient length of stay, quality of life
      (EuroQol questionnaire), the Functional Independence Measure (FIM), and health
      utilization and cost data. Secondary outcomes will assess clinical outcomes
      relevant to the goals of therapy: the 10 metre walk test, the timed up and go
      test, the Personal Care Participation Assessment and Resource Tool (PC PART), and
      the modified motor assessment scale. Blinded assessors will assess outcomes at
      admission and discharge, and follow up data on quality of life, function and
      health care costs will be collected at 6 and 12 months after discharge. Between
      group differences will be analysed with analysis of covariance using baseline
      measures as the covariate. A health economic analysis will be carried out
      alongside the randomised controlled trial. DISCUSSION: This paper outlines the
      study protocol for the first fully powered randomised controlled trial
      incorporating a health economic analysis to establish if additional Saturday
      allied health services for rehabilitation inpatients reduces length of stay
      without compromising discharge outcomes. If successful, this trial will have
      substantial health benefits for the patients and for organizations delivering
      rehabilitation services. CLINICAL TRIAL REGISTRATION NUMBER: Australian and New
      Zealand Clinical Trials Registry ACTRN12609000973213.

PMID- 21073704
TI  - Moving towards a complete molecular framework of the Nematoda: a focus on the
      Enoplida and early-branching clades.
AB  - BACKGROUND: The subclass Enoplia (Phylum Nematoda) is purported to be the
      earliest branching clade amongst all nematode taxa, yet the deep phylogeny of
      this important lineage remains elusive. Free-living marine species within the
      order Enoplida play prominent roles in marine ecosystems, but previous molecular
      phylogenies have provided only the briefest evolutionary insights; this study
      aimed to firmly resolve internal relationships within the hyper-diverse but
      poorly understood Enoplida. In addition, we revisited the molecular framework of
      the Nematoda using a rigorous phylogenetic approach in order to investigate
      patterns of early splits amongst the oldest lineages (Dorylaimia and Enoplia).
      RESULTS: Morphological identifications, nuclear gene sequences (18S and 28S
      rRNA), and mitochondrial gene sequences (cox1) were obtained from marine Enoplid
      specimens representing 37 genera. The 18S gene was used to resolve deep splits
      within the Enoplia and evaluate the branching order of major clades in the
      nematode tree; multiple phylogenetic methods and rigorous empirical tests were
      carried out to assess tree topologies under different parameters and combinations
      of taxa. Significantly increased taxon sampling within the Enoplida resulted in a
      well-supported, robust phylogenetic topology of this group, although the
      placement of certain clades was not fully resolved. Our analysis could not
      unequivocally confirm the earliest splits in the nematode tree, and outgroup
      choice significantly affected the observed branching order of the Dorylaimia and
      Enoplia. Both 28S and cox1 were too variable to infer deep phylogeny, but
      provided additional insight at lower taxonomic levels. CONCLUSIONS: Analysis of
      internal relationships reveals that the Enoplia is split into two main clades,
      with groups consisting of terrestrial (Triplonchida) and primarily marine fauna
      (Enoplida). Five independent lineages were recovered within the Enoplida,
      containing a mixture of marine and terrestrial species; clade structure suggests
      that habitat transitions have occurred at least four times within this group.
      Unfortunately, we were unable to obtain a consistent or well-supported topology
      amongst early-branching nematode lineages. It appears unlikely that single-gene
      phylogenies using the conserved 18S gene will be useful for confirming the
      branching order at the base of the nematode tree-future efforts will require
      multi-gene analyses or phylogenomic methods.

PMID- 21073705
TI  - Evaluation of EMG processing techniques using Information Theory.
AB  - BACKGROUND: Electromyographic signals can be used in biomedical engineering
      and/or rehabilitation field, as potential sources of control for prosthetics and
      orthotics. In such applications, digital processing techniques are necessary to
      follow efficient and effectively the changes in the physiological characteristics
      produced by a muscular contraction. In this paper, two methods based on
      information theory are proposed to evaluate the processing techniques. METHODS:
      These methods determine the amount of information that a processing technique is
      able to extract from EMG signals. The processing techniques evaluated with these
      methods were: absolute mean value (AMV), RMS values, variance values (VAR) and
      difference absolute mean value (DAMV). EMG signals from the middle deltoid during
      abduction and adduction movement of the arm in the scapular plane was registered,
      for static and dynamic contractions. The optimal window length (segmentation),
      abduction and adduction movements and inter-electrode distance were also
      analyzed. RESULTS: Using the optimal segmentation (200 ms and 300 ms in static
      and dynamic contractions, respectively) the best processing techniques were: RMS,
      AMV and VAR in static contractions, and only the RMS in dynamic contractions.
      Using the RMS of EMG signal, variations in the amount of information between the
      abduction and adduction movements were observed. CONCLUSIONS: Although the
      evaluation methods proposed here were applied to standard processing techniques,
      these methods can also be considered as alternatives tools to evaluate new
      processing techniques in different areas of electrophysiology.

PMID- 21073706
TI  - Epigenetic domains found in mouse embryonic stem cells via a hidden Markov model.
AB  - BACKGROUND: Epigenetics is an important layer of transcriptional control
      necessary for cell-type specific gene regulation. Recent studies have shown
      significant epigenetic patterns associated with developmental stages and
      diseases. However, previous studies have been mostly limited to focal epigenetic
      patterns, whereas methods for analyzing large-scale organizations are still
      lacking. RESULTS: We developed a hidden Markov model (HMM) approach for detecting
      the types and locations of epigenetic domains from multiple histone
      modifications. We used this method to analyze a published ChIP-seq dataset of
      five histone modification marks (H3K4me2, H3K4me3, H3K27me3, H3K9me3, and
      H3K36me3) in mouse embryonic stem (ES) cells. We identified three types of
      domains, corresponding to active, non-active, and null states. In total, our
      three-state HMM identified 258 domains in the mouse genome containing 9.6 genes
      on average. These domains were validated by a number of criteria. The largest
      domains correspond to olfactory receptor (OR) gene clusters. Each Hox gene
      cluster also forms a separate epigenetic domain. We found that each type of
      domain is associated with distinct biological functions and structural changes
      during early cell differentiation. CONCLUSIONS: The HMM approach successfully
      detects domains of consistent epigenetic patterns from ChIP-seq data, providing
      new insights into the role of epigenetics in long-range gene regulation.

PMID- 21073707
TI  - Racial differences in treatment and survival in older patients with diffuse large
      B-cell lymphoma (DLBCL).
AB  - BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in
      the United States. Although it is an aggressive type of lymphoma, 40% to 50% of
      patients are cured with treatment. The study objectives were to identify patient
      factors associated with treatment and survival in DLBCL. METHODS: Using
      Surveillance, Epidemiology, and End Results (SEER) registry data linked to
      Medicare claims, we identified 7,048 patients diagnosed with DLBCL between
      January 1, 2001 and December 31, 2005. Patients were followed from diagnosis
      until the end of their claims history (maximum December 31, 2007) or death.
      Medicare claims were used to characterize the first infused chemo-immunotherapy
      (C-I therapy) regimen and to identify radiation. Multivariate analyses were
      performed to identify patient demographic, socioeconomic, and clinical factors
      associated with treatment and with survival. Outcomes variables in the survival
      analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and
      other/unknown cause mortality. RESULTS: Overall, 84% (n = 5,887) received C-I
      therapy or radiation treatment during the observation period: both, 26%; C-I
      therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77
      years, 54% were female, 88% were white, and 43% had Stage III or IV disease at
      diagnosis. The median time to first treatment was 42 days, and 92% of these
      patients had received their first treatment by day 180 following diagnosis. In
      multivariate analysis, the treatment rate was significantly lower among patients
      >= 80 years old, blacks versus whites, those living in a census tract with >= 12%
      poverty, and extra-nodal disease. Blacks had a lower treatment rate overall
      (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment
      within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In
      multivariate survival analysis, black race was associated with higher all-cause
      mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1.35; P =
      0.01), but not mortality due to NHL (HR 1.16; P = 0.19). CONCLUSIONS: In elderly
      patients diagnosed with DLBCL, there are large differences in treatment access
      and survival between blacks and whites.

PMID- 21073708
TI  - Absence of IFNgamma expression induces neuronal degeneration in the spinal cord
      of adult mice.
AB  - BACKGROUND: Interferon gamma (IFNgamma) is a pro-inflammatory cytokine, which may
      be up-regulated after trauma to the peripheral or central nervous system. Such
      changes include reactive gliosis and synaptic plasticity that are considered
      important responses to the proper regenerative response after injury. Also,
      IFNgamma is involved in the upregulation of the major histocompatibility complex
      class I (MHC class I), which has recently been shown to play an important role in
      the synaptic plasticity process following axotomy. There is also evidence that
      IFNgamma may interfere in the differentiation and survival of neuronal cells.
      However, little is known about the effects of IFNgamma absence on spinal cord
      neurons after injury. METHODS: We performed a unilateral sciatic nerve
      transection injury in C57BL/6J (wild type) and IFNgamma-KO (mutant) mice and
      studied motoneuron morphology using light and electron microscopy. One week after
      the lesion, mice from both strains were sacrificed and had their lumbar spinal
      cords processed for histochemistry (n = 5 each group) and transmission electron
      microscopy (TEM, n = 5 each group). Spinal cord sections from non-lesioned
      animals were also used to investigate neuronal survival and the presence of
      apoptosis with TUNEL and immunohistochemistry. RESULTS: We find that presumed
      motoneurons in the lower lumbar ventral horn exhibited a smaller soma size in the
      IFNgamma-KO series, regardless of nerve lesion. In plastic embedded sections
      stained with toluidine blue, the IFNgamma-KO mice demonstrated a greater
      proportion of degenerating neurons in the ventral horn when compared to the
      control series (p < 0.05). Apoptotic death is suggested based on TUNEL and
      caspase 3 immunostaining. A sciatic nerve axotomy did not further aggravate the
      neuronal loss. The cellular changes were supported by electron microscopy, which
      demonstrated ventral horn neurons exhibiting intracellular vacuoles as well as
      degenerating nuclei and cytoplasm in the IFNgamma-KO mice. Adjacent glial cells
      showed features suggestive of phagocytosis. Additional ultrastructural studies
      showed a decreased number of pre-synaptic terminals apposing to motoneurons in
      mutant mice. Nevertheless, no statistical difference regarding the input covering
      could be detected among the studied strains. CONCLUSION: Altogether, these
      results suggest that IFNgamma may be neuroprotective and its absence results in
      neuronal death, which is not further increased by peripheral axotomy.

PMID- 21073709
TI  - The use of opioids at the end of life: the knowledge level of Dutch physicians as
      a potential barrier to effective pain management.
AB  - BACKGROUND: Pain is still one of the most frequently occurring symptoms at the
      end of life, although it can be treated satisfactorily in most cases if the
      physician has adequate knowledge. In the Netherlands, almost 60% of the patients
      with non-acute illnesses die at home where end of life care is coordinated by the
      general practitioner (GP); about 30% die in hospitals (cared for by clinical
      specialists), and about 10% in nursing homes (cared for by elderly care
      physicians).The research question of this study is: what is the level of
      knowledge of Dutch physicians concerning pain management and the use of opioids
      at the end of life? METHODS: A written questionnaire was sent to a random sample
      of physicians of specialties most often involved in end of life care in the
      Netherlands. The questionnaire was completed by 406 physicians, response rate
      41%. RESULTS: Almost all physicians were aware of the most basal knowledge about
      opioids, e.g. that it is important for treatment purposes to distinguish
      nociceptive from neuropathic pain (97%). Approximately half of the physicians
      (46%) did not know that decreased renal function raises plasma concentration of
      morphine(-metabolites) and 34% of the clinical specialists erroneously thought
      opioids are the favoured drug for palliative sedation.Although 91% knew that
      opioids titrated against pain do not shorten life, 10% sometimes or often gave
      higher dosages than needed with the explicit aim to hasten death. About half felt
      sometimes or often pressured by relatives to hasten death by increasing
      opioiddosage.The large majority (83%) of physicians was interested in additional
      education about subjects related to the end of life, the most popular subject was
      opioid rotation (46%). CONCLUSIONS: Although the basic knowledge of physicians
      was adequate, there seemed to be a lack of knowledge in several areas, which can
      be a barrier for good pain management at the end of life. From this study four
      areas emerge, in which it seems likely that an improvement can improve the
      quality of pain management at the end of life for many patients in the
      Netherlands: 1)palliative sedation; 2)expected effect of opioids on survival; and
      3) opioid rotation.

PMID- 21073711
TI  - Leukocyte nucleus segmentation and nucleus lobe counting.
AB  - BACKGROUND: Leukocytes play an important role in the human immune system. The
      family of leukocytes is comprised of lymphocytes, monocytes, eosinophils,
      basophils, and neutrophils. Any infection or acute stress may increase or
      decrease the number of leukocytes. An increased percentage of neutrophils may be
      caused by an acute infection, while an increased percentage of lymphocytes can be
      caused by a chronic bacterial infection. It is important to realize an abnormal
      variation in the leukocytes. The five types of leukocytes can be distinguished by
      their cytoplasmic granules, staining properties of the granules, size of cell,
      the proportion of the nuclear to the cytoplasmic material, and the type of
      nucleolar lobes. The number of lobes increased when leukemia, chronic nephritis,
      liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred.
      Clinical neutrophil hypersegmentation has been widely used as an indicator of B12
      or folate deficiency.Biomedical technologists can currently recognize abnormal
      leukocytes using human eyes. However, the quality and efficiency of diagnosis may
      be compromised due to the limitations of the biomedical technologists' eyesight,
      strength, and medical knowledge. Therefore, the development of an automatic
      leukocyte recognition system is feasible and necessary. It is essential to
      extract the leukocyte region from a blood smear image in order to develop an
      automatic leukocyte recognition system. The number of lobes increased when
      leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or
      folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely
      used as an indicator of B12 or folate deficiency. RESULTS: The purpose of this
      paper is to contribute an automatic leukocyte nuclei image segmentation method
      for such recognition technology. The other goal of this paper is to develop the
      method of counting the number of lobes in a cell nucleus. The experimental
      results demonstrated impressive segmentation accuracy. CONCLUSIONS: Insensitive
      to the variance of images, the LNS (Leukocyte Nuclei Segmentation) method
      functioned well to isolate the leukocyte nuclei from a blood smear image with
      much better UR (Under Segmentation Rate), ER (Overall Error Rate), and RDE
      (Relative Distance Error). The presented LC (Lobe Counting) method is capable of
      splitting leukocyte nuclei into lobes. The experimental results illuminated that
      both methods can give expressive performances. In addition, three advanced image
      processing techniques were proposed as weighted Sobel operator, GDW (Gradient
      Direction Weight), and GBPD (Genetic-based Parameter Detector).

PMID- 21073710
TI  - Maternal common mental disorders and infant development in Ethiopia: the P-MaMiE
      Birth Cohort.
AB  - BACKGROUND: Chronicity and severity of early exposure to maternal common mental
      disorders (CMD) has been associated with poorer infant development in high-income
      countries. In low- and middle-income countries (LAMICs), perinatal CMD is
      inconsistently associated with infant development, but the impact of severity and
      persistence has not been examined. METHODS: A nested population-based cohort of
      258 pregnant women was identified from the Perinatal Maternal Mental Disorder in
      Ethiopia (P-MaMiE) study, and 194 (75.2%) were successfully followed up until the
      infants were 12 months of age. Maternal CMD was measured in pregnancy and at two
      and 12 months postnatal using the WHO Self-Reporting Questionnaire, validated for
      use in this setting. Infant outcomes were evaluated using the Bayley Scales of
      Infant Development. RESULTS: Antenatal maternal CMD symptoms were associated with
      poorer infant motor development (beta^ -0.20; 95% CI: -0.37 to -0.03), but this
      became non-significant after adjusting for confounders. Postnatal CMD symptoms
      were not associated with any domain of infant development. There was evidence of
      a dose-response relationship between the number of time-points at which the
      mother had high levels of CMD symptoms (SRQ >= 6) and impaired infant motor
      development (beta^ = -0.80; 95%CI -2.24, 0.65 for ante- or postnatal CMD only,
      beta^ = -4.19; 95%CI -8.60, 0.21 for ante- and postnatal CMD, compared to no CMD;
      test-for-trend chi(2)13.08(1), p < 0.001). Although this association became non
      significant in the fully adjusted model, the beta^ coefficients were unchanged
      indicating that the relationship was not confounded. In multivariable analyses,
      lower socio-economic status and lower infant weight-for-age were associated with
      significantly lower scores on both motor and cognitive developmental scales.
      Maternal experience of physical violence was significantly associated with
      impaired cognitive development. CONCLUSIONS: The study supports the hypothesis
      that it is the accumulation of risk exposures across time rather than early
      exposure to maternal CMD per se that is more likely to affect child development.
      Further investigation of the impact of chronicity of maternal CMD upon child
      development in LAMICs is indicated. In the Ethiopian setting, poverty,
      interpersonal violence and infant undernutrition should be targets for
      interventions to reduce the loss of child developmental potential.

PMID- 21073712
TI  - Physical activity as a treatment for depression: the TREAD randomised trial
      protocol.
AB  - BACKGROUND: Depression is one of the most common reasons for consulting a General
      Practitioner (GP) within the UK. Whilst antidepressants have been shown to be
      clinically effective, many patients and healthcare professionals would like to
      access other forms of treatment as an alternative or adjunct to drug therapy for
      depression. A recent systematic review presented some evidence that physical
      activity could offer one such option, although further investigation is needed to
      test its effectiveness within the context of the National Health Service.The aim
      of this paper is to describe the protocol for a randomised, controlled trial
      (RCT) designed to evaluate an intervention developed to increase physical
      activity as a treatment for depression within primary care. METHODS/DESIGN: The
      TREAD study is a pragmatic, multi-centre, two-arm RCT which targets patients
      presenting with a new episode of depression. Patients were approached if they
      were aged 18-69, had recently consulted their GP for depression and, where
      appropriate, had been taking antidepressants for less than one month. Only those
      patients with a confirmed diagnosis of a depressive episode as assessed by the
      Clinical Interview Schedule-Revised (CIS-R), a Beck Depression Inventory (BDI)
      score of at least 14 and informed written consent were included in the study.
      Eligible patients were individually randomised to one of two treatment groups;
      usual GP care or usual GP care plus facilitated physical activity. The primary
      outcome of the trial is clinical symptoms of depression assessed using the BDI
      four months after randomisation. A number of secondary outcomes are also measured
      at the 4-, 8- and 12-month follow-up points including quality of life, attitude
      to and involvement in physical activity and antidepressant use/adherence.
      Outcomes will be analysed on an intention-to-treat (ITT) basis and will use
      linear and logistic regression models to compare treatments. DISCUSSION: The
      results of the trial will provide information about the effectiveness of physical
      activity as a treatment for depression. Given the current prevalence of
      depression and its associated economic burden, it is hoped that TREAD will
      provide a timely contribution to the evidence on treatment options for patients,
      clinicians and policy-makers. TRIAL REGISTRATION: ISRCTN 16900744.

PMID- 21073713
TI  - Protein complex forming ability is favored over the features of interacting
      partners in determining the evolutionary rates of proteins in the yeast protein
      protein interaction networks.
AB  - BACKGROUND: Evolutionary rates of proteins in a protein-protein interaction
      network are primarily governed by the protein connectivity and/or expression
      level. A recent study revealed the importance of the features of the interacting
      protein partners, viz., the coefficient of functionality and clustering
      coefficient in controlling the protein evolutionary rates in a protein-protein
      interaction (PPI) network. RESULTS: By multivariate regression analysis we found
      that the three parameters: probability of complex formation, expression level and
      degree of a protein independently guide the evolutionary rates of proteins in the
      PPI network. The contribution of the complex forming property of a protein and
      its expression level led to nearly 43% of the total variation as observed from
      the first principal component. We also found that for complex forming proteins in
      the network, those which have partners sharing the same functional class evolve
      faster than those having partners belonging to different functional classes. The
      proteins in the dense parts of the network evolve faster than their counterparts
      which are present in the sparse regions of the network. Taking into account the
      complex forming ability, we found that all the complex forming proteins
      considered in this study evolve slower than the non-complex forming proteins
      irrespective of their localization in the network or the affiliation of their
      partners to same/different functional classes. CONCLUSIONS: We have shown here
      that the functionality and clustering coefficient correlated with the degree of
      the protein in the protein-protein interaction network. We have identified the
      significant relationship of the complex-forming property of proteins and their
      evolutionary rates even when they are classified according to the features of
      their interacting partners. Our study implies that the evolutionarily constrained
      proteins are actually members of a larger number of protein complexes and this
      justifies why they have enhanced expression levels.

PMID- 21073714
TI  - What are the basic self-monitoring components for cardiovascular risk management?
AB  - BACKGROUND: Self-monitoring is increasingly recommended as a method of managing
      cardiovascular disease. However, the design, implementation and reproducibility
      of the self-monitoring interventions appear to vary considerably. We examined the
      interventions included in systematic reviews of self-monitoring for four clinical
      problems that increase cardiovascular disease risk. METHODS: We searched Medline
      and Cochrane databases for systematic reviews of self-monitoring for: heart
      failure, oral anticoagulation therapy, hypertension and type 2 diabetes. We
      extracted data using a pre-specified template for the identifiable components of
      the interventions for each disease. Data was also extracted on the theoretical
      basis of the education provided, the rationale given for the self-monitoring
      regime adopted and the compliance with the self-monitoring regime by the
      patients. RESULTS: From 52 randomized controlled trials (10,388 patients) we
      identified four main components in self-monitoring interventions: education, self
      measurement, adjustment/adherence and contact with health professionals.
      Considerable variation in these components occurred across trials and conditions,
      and often components were poorly described. Few trials gave evidence-based
      rationales for the components included and self-measurement regimes adopted.
      CONCLUSIONS: The components of self-monitoring interventions are not well defined
      despite current guidelines for self-monitoring in cardiovascular disease
      management. Few trials gave evidence-based rationales for the components included
      and self-measurement regimes adopted. We propose a checklist of factors to be
      considered in the design of self-monitoring interventions which may aid in the
      provision of an evidence-based rationale for each component as well as increase
      the reproducibility of effective interventions for clinicians and researchers.

PMID- 21073715
TI  - Prenatal exposure of ethanol induces increased glutamatergic neuronal
      differentiation of neural progenitor cells.
AB  - BACKGROUND: Prenatal ethanol exposure during pregnancy induces a spectrum of
      mental and physical disorders called fetal alcohol spectrum disorder (FASD). The
      central nervous system is the main organ influenced by FASD, and neurological
      symptoms include mental retardation, learning abnormalities, hyperactivity and
      seizure susceptibility in childhood along with the microcephaly. In this study,
      we examined whether ethanol exposure adversely affects the proliferation of NPC
      and de-regulates the normal ratio between glutamatergic and GABAergic neuronal
      differentiation using primary neural progenitor culture (NPC) and in vivo FASD
      models. METHODS: Neural progenitor cells were cultured from E14 embryo brain of
      Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4
      g/kg/day) diluted with normal saline from E7 to E16 for in vivo FASD animal
      models. Expression level of proteins was investigated by western blot analysis
      and immunocytochemical assays. MTT was used for cell viability. Proliferative
      activity of NPCs was identified by BrdU incorporation, immunocytochemistry and
      FACS analysis. RESULTS: Reduced proliferation of NPCs by ethanol was demonstrated
      using BrdU incorporation, immunocytochemistry and FACS analysis. In addition,
      ethanol induced the imbalance between glutamatergic and GABAergic neuronal
      differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD
      with concomitant decrease in the expression of Mash1. Similar pattern of
      expression of those transcription factors was observed using an in vivo model of
      FASD as well as the increased expression of PSD-95 and decreased expression of
      GAD67. CONCLUSIONS: These results suggest that ethanol induces hyper
      differentiation of glutamatergic neuron through Pax6 pathway, which may underlie
      the hyper-excitability phenotype such as hyperactivity or seizure susceptibility
      in FASD patients.

PMID- 21073716
TI  - EcoTILLING in Capsicum species: searching for new virus resistances.
AB  - BACKGROUND: The EcoTILLING technique allows polymorphisms in target genes of
      natural populations to be quickly analysed or identified and facilitates the
      screening of genebank collections for desired traits. We have developed an
      EcoTILLING platform to exploit Capsicum genetic resources. A perfect example of
      the utility of this EcoTILLING platform is its application in searching for new
      virus-resistant alleles in Capsicum genus. Mutations in translation initiation
      factors (eIF4E, eIF(iso)4E, eIF4G and eIF(iso)4G) break the cycle of several RNA
      viruses without affecting the plant life cycle, which makes these genes potential
      targets to screen for resistant germplasm. RESULTS: We developed and assayed a
      cDNA-based EcoTILLING platform with 233 cultivated accessions of the genus
      Capsicum. High variability in the coding sequences of the eIF4E and eIF(iso)4E
      genes was detected using the cDNA platform. After sequencing, 36 nucleotide
      changes were detected in the CDS of eIF4E and 26 in eIF(iso)4E. A total of 21
      eIF4E haplotypes and 15 eIF(iso)4E haplotypes were identified. To evaluate the
      functional relevance of this variability, 31 possible eIF4E/eIF(iso)4E
      combinations were tested against Potato virus Y. The results showed that five new
      eIF4E variants (pvr2(10), pvr2(11), pvr2(12), pvr2(13) and pvr2(14)) were related
      to PVY-resistance responses. CONCLUSIONS: EcoTILLING was optimised in different
      Capsicum species to detect allelic variants of target genes. This work is the
      first to use cDNA instead of genomic DNA in EcoTILLING. This approach avoids
      intronic sequence problems and reduces the number of reactions. A high level of
      polymorphism has been identified for initiation factors, showing the high genetic
      variability present in our collection and its potential use for other traits,
      such as genes related to biotic or abiotic stresses, quality or production.
      Moreover, the new eIF4E and eIF(iso)4E alleles are an excellent collection for
      searching for new resistance against other RNA viruses.

PMID- 21073717
TI  - Efficacy, effectiveness, and behavior change trials in exercise research.
AB  - BACKGROUND: The widespread incorporation of behavioral support interventions into
      exercise trials has sometimes caused confusion concerning the primary purpose of
      a trial. The purpose of the present paper is to offer some conceptual and
      methodological distinctions among three types of exercise trials with a view
      towards improving their design, conduct, reporting, and interpretation.
      DISCUSSION: Exercise trials can be divided into "health outcome trials" or
      "behavior change trials" based on their primary outcome. Health outcome trials
      can be further divided into efficacy and effectiveness trials based on their
      potential for dissemination into practice. Exercise efficacy trials may achieve
      high levels of exercise adherence by supervising the exercise over a short
      intervention period ("traditional" exercise efficacy trials) or by the adoption
      of an extensive behavioral support intervention designed to accommodate
      unsupervised exercise and/or an extended intervention period ("contemporary"
      exercise efficacy trials). Exercise effectiveness trials may emanate from the
      desire to test exercise interventions with proven efficacy ("traditional"
      exercise effectiveness trials) or the desire to test behavioral support
      interventions with proven feasibility ("contemporary" exercise effectiveness
      trials). Efficacy, effectiveness, and behavior change trials often differ in
      terms of their primary and secondary outcomes, theoretical models adopted,
      selection of participants, nature of the exercise and comparison interventions,
      nature of the behavioral support intervention, sample size calculation, and
      interpretation of trial results. SUMMARY: Exercise researchers are encouraged to
      clarify the primary purpose of their trial to facilitate its design, conduct, and
      interpretation.

PMID- 21073718
TI  - A functional henipavirus envelope glycoprotein pseudotyped lentivirus assay
      system.
AB  - BACKGROUND: Hendra virus (HeV) and Nipah virus (NiV) are newly emerged zoonotic
      paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and
      peninsular Malaysia in 1998/9 respectively and classified within the new
      Henipavirus genus. Both viruses can infect a broad range of mammalian species
      causing severe and often-lethal disease in humans and animals, and repeated
      outbreaks continue to occur. Extensive laboratory studies on the host cell
      infection stage of HeV and NiV and the roles of their envelope glycoproteins have
      been hampered by their highly pathogenic nature and restriction to biosafety
      level-4 (BSL-4) containment. To circumvent this problem, we have developed a
      henipavirus envelope glycoprotein pseudotyped lentivirus assay system using
      either a luciferase gene or green fluorescent protein (GFP) gene encoding human
      immunodeficiency virus type-1 (HIV-1) genome in conjunction with the HeV and NiV
      fusion (F) and attachment (G) glycoproteins. RESULTS: Functional retrovirus
      particles pseudotyped with henipavirus F and G glycoproteins displayed proper
      target cell tropism and entry and infection was dependent on the presence of the
      HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity
      of the assay was confirmed by the lack of reporter-gene signals when particles
      bearing either only the F or only G glycoprotein were prepared and assayed. Virus
      entry could be specifically blocked when infection was carried out in the
      presence of a fusion inhibiting C-terminal heptad (HR-2) peptide, a well
      characterized, cross-reactive, neutralizing human mAb specific for the
      henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition,
      the utility of the assay was also demonstrated by an examination of the influence
      of the cytoplasmic tail of F in its fusion activity and incorporation into
      pseudotyped virus particles by generating and testing a panel of truncation
      mutants of NiV and HeV F. CONCLUSIONS: Together, these results demonstrate that a
      specific henipavirus entry assay has been developed using NiV or HeV F and G
      glycoprotein pseudotyped reporter-gene encoding retrovirus particles. This assay
      can be conducted safely under BSL-2 conditions and will be a useful tool for
      measuring henipavirus entry and studying F and G glycoprotein function in the
      context of virus entry, as well as in assaying and characterizing neutralizing
      antibodies and virus entry inhibitors.

PMID- 21073719
TI  - Metagenomic analysis of the turkey gut RNA virus community.
AB  - Viral enteric disease is an ongoing economic burden to poultry producers
      worldwide, and despite considerable research, no single virus has emerged as a
      likely causative agent and target for prevention and control efforts.
      Historically, electron microscopy has been used to identify suspect viruses, with
      many small, round viruses eluding classification based solely on morphology.
      National and regional surveys using molecular diagnostics have revealed that
      suspect viruses continuously circulate in United States poultry, with many
      viruses appearing concomitantly and in healthy birds. High-throughput nucleic
      acid pyrosequencing is a powerful diagnostic technology capable of determining
      the full genomic repertoire present in a complex environmental sample. We
      utilized the Roche/454 Life Sciences GS-FLX platform to compile an RNA virus
      metagenome from turkey flocks experiencing enteric disease. This approach yielded
      numerous sequences homologous to viruses in the BLAST nr protein database, many
      of which have not been described in turkeys. Our analysis of this turkey gut RNA
      metagenome focuses in particular on the turkey-origin members of the
      Picornavirales, the Caliciviridae, and the turkey Picobirnaviruses.

PMID- 21073720
TI  - Module detection in complex networks using integer optimisation.
AB  - BACKGROUND: The detection of modules or community structure is widely used to
      reveal the underlying properties of complex networks in biology, as well as
      physical and social sciences. Since the adoption of modularity as a measure of
      network topological properties, several methodologies for the discovery of
      community structure based on modularity maximisation have been developed.
      However, satisfactory partitions of large graphs with modest computational
      resources are particularly challenging due to the NP-hard nature of the related
      optimisation problem. Furthermore, it has been suggested that optimising the
      modularity metric can reach a resolution limit whereby the algorithm fails to
      detect smaller communities than a specific size in large networks. RESULTS: We
      present a novel solution approach to identify community structure in large
      complex networks and address resolution limitations in module detection. The
      proposed algorithm employs modularity to express network community structure and
      it is based on mixed integer optimisation models. The solution procedure is
      extended through an iterative procedure to diminish effects that tend to
      agglomerate smaller modules (resolution limitations). CONCLUSIONS: A
      comprehensive comparative analysis of methodologies for module detection based on
      modularity maximisation shows that our approach outperforms previously reported
      methods. Furthermore, in contrast to previous reports, we propose a strategy to
      handle resolution limitations in modularity maximisation. Overall, we illustrate
      ways to improve existing methodologies for community structure identification so
      as to increase its efficiency and applicability.

PMID- 21073721
TI  - Unmet needs, quality of life and support networks of people with dementia living
      at home.
AB  - BACKGROUND: There is lack of evidence about the unmet needs of people with
      dementia (PWD) living at home and the predictors of high levels of unmet needs.
      The main aim of this study was to identify the relationship between unmet needs,
      social networks and quality of life of PWD living at home. METHODS: One hundred
      and fifty two community dwelling PWD and 128 carers were interviewed about PWD's
      needs, social networks, quality of life and other functional and psychological
      factors. All the interviews with PWD were carried out at their homes. Interviews
      with carers were undertaken either at PWD's home, their own home or at the health
      centre. Whenever possible, PWD and carers were interviewed separately. The data
      collection took place between November 2005 and July 2007. The majority of
      participants (129, 84.9%) were recruited from National Health Services (NHS) and
      the rest (23, 15.1%) were recruited from other organisations such as social
      services and voluntary organizations in the UK. RESULTS: The most frequent unmet
      needs for PWD were daytime activities (77, 50.7%), company (60, 39.5%), and help
      with psychological distress (47, 30.9%). Higher number of behavioural and
      psychological symptoms, low-community involvement social networks, having a
      younger carer and higher carer's anxiety were found to be predictors of higher
      unmet needs in PWD. Social networks and behavioural and psychological symptoms
      had an indirect effect on PWD's self-rated quality of life through unmet needs.
      CONCLUSIONS: Interventions aiming to reduce unmet needs, through the treatment of
      behavioural and psychological symptoms and the involvement of PWD in the
      community, would potentially improve PWD's quality of life.

PMID- 21073722
TI  - Single-cell qPCR on dispersed primary pituitary cells -an optimized protocol.
AB  - BACKGROUND: The incidence of false positives is a potential problem in single
      cell PCR experiments. This paper describes an optimized protocol for single-cell
      qPCR measurements in primary pituitary cell cultures following patch-clamp
      recordings. Two different cell harvesting methods were assessed using both the
      GH4 prolactin producing cell line from rat, and primary cell culture from fish
      pituitaries. RESULTS: Harvesting whole cells followed by cell lysis and qPCR
      performed satisfactory on the GH4 cell line. However, harvesting of whole cells
      from primary pituitary cultures regularly produced false positives, probably due
      to RNA leakage from cells ruptured during the dispersion of the pituitary cells.
      To reduce RNA contamination affecting the results, we optimized the conditions by
      harvesting only the cytosol through a patch pipette, subsequent to
      electrophysiological experiments. Two important factors proved crucial for
      reliable harvesting. First, silanizing the patch pipette glass prevented foreign
      extracellular RNA from attaching to charged residues on the glass surface.
      Second, substituting the commonly used perforating antibiotic amphotericin B with
      beta-escin allowed efficient cytosol harvest without loosing the giga seal.
      Importantly, the two harvesting protocols revealed no difference in RNA isolation
      efficiency. CONCLUSION: Depending on the cell type and preparation, validation of
      the harvesting technique is extremely important as contaminations may give false
      positives. Here we present an optimized protocol allowing secure harvesting of
      RNA from single cells in primary pituitary cell culture following perforated
      whole cell patch clamp experiments.

PMID- 21073723
TI  - Sequencing of 6.7 Mb of the melon genome using a BAC pooling strategy.
AB  - BACKGROUND: Cucumis melo (melon) belongs to the Cucurbitaceae family, whose
      economic importance among horticulture crops is second only to Solanaceae. Melon
      has a high intra-specific genetic variation, morphologic diversity and a small
      genome size (454 Mb), which make it suitable for a great variety of molecular and
      genetic studies. A number of genetic and genomic resources have already been
      developed, such as several genetic maps, BAC genomic libraries, a BAC-based
      physical map and EST collections. Sequence information would be invaluable to
      complete the picture of the melon genomic landscape, furthering our understanding
      of this species' evolution from its relatives and providing an important genetic
      tool. However, to this day there is little sequence data available, only a few
      melon genes and genomic regions are deposited in public databases. The
      development of massively parallel sequencing methods allows envisaging new
      strategies to obtain long fragments of genomic sequence at higher speed and lower
      cost than previous Sanger-based methods. RESULTS: In order to gain insight into
      the structure of a significant portion of the melon genome we set out to perform
      massive sequencing of pools of BAC clones. For this, a set of 57 BAC clones from
      a double haploid line was sequenced in two pools with the 454 system using both
      shotgun and paired-end approaches. The final assembly consists of an estimated
      95% of the actual size of the melon BAC clones, with most likely complete
      sequences for 50 of the BACs, and a total sequence coverage of 39x. The accuracy
      of the assembly was assessed by comparing the previously available Sanger
      sequence of one of the BACs against its 454 sequence, and the polymorphisms found
      involved only 1.7 differences every 10,000 bp that were localized in 15
      homopolymeric regions and two dinucleotide tandem repeats. Overall, the study
      provides approximately 6.7 Mb or 1.5% of the melon genome. The analysis of this
      new data has allowed us to gain further insight into characteristics of the melon
      genome such as gene density, average protein length, or microsatellite and
      transposon content. The annotation of the BAC sequences revealed a high degree of
      collinearity and protein sequence identity between melon and its close relative
      Cucumis sativus (cucumber). Transposon content analysis of the syntenic regions
      suggests that transposition activity after the split of both cucurbit species has
      been low in cucumber but very high in melon. CONCLUSIONS: The results presented
      here show that the strategy followed, which combines shotgun and BAC-end
      sequencing together with anchored marker information, is an excellent method for
      sequencing specific genomic regions, especially from relatively compact genomes
      such as that of melon. However, in agreement with other results, this map-based,
      BAC approach is confirmed to be an expensive way of sequencing a whole plant
      genome. Our results also provide a partial description of the melon genome's
      structure. Namely, our analysis shows that the melon genome is highly collinear
      with the smaller one of cucumber, the size difference being mainly due to the
      expansion of intergenic regions and proliferation of transposable elements.

PMID- 21073724
TI  - Temporomandibular joint disc repositioning using bone anchors: an immediate post
      surgical evaluation by magnetic resonance imaging.
AB  - BACKGROUND: Open joint procedures using bone anchors have shown clinical and
      radiograph good success, but post surgical disc position has not been documented
      with MRI imaging. We have designed a modified technique of using two bone anchors
      and 2 sutures to reposition the articular discs. This MRI study evaluates the
      post surgical success of this technique to reposition and stabilize the TMJ
      articular discs. METHODS: Consecutive 81 patients with unilateral TMJ internal
      derangement (ID) (81 TMJs) were treated between December 1, 2003, and December 1,
      2006, at the Department of Oral and Maxillofacial Surgery, Ninth Peoples
      Hospital, Shanghai, Jiao Tong University School of Medicine. All patients were
      subjected to magnetic resonance imaging before and one to seven days post surgery
      to determine disc position using the modified bone anchor technique. RESULTS:
      Postoperative MRIs (one to seven days) confirm that 77 of 81 joints were
      identified as excellent results and one joint was considered good for an overall
      effective rate of 96.3% (78 of 81 joints). Only 3.7% (3 of 81) of the joints were
      designated as poor results requiring a second open surgery. CONCLUSIONS: This
      procedure has provided successful repositioning of the articular discs in
      unilateral TMJ ID at one to seven days post surgery.

PMID- 21073725
TI  - Phylogenetic analysis of Croatian orf viruses isolated from sheep and goats.
AB  - BACKGROUND: The Orf virus (ORFV) is the prototype of the parapoxvirus genus and
      it primarily causes contagious ecthyma in goats, sheep, and other ruminants
      worldwide. In this paper, we described the sequence and phylogenetic analysis of
      the B2L gene of ORFV from two natural outbreaks: i) in autochthonous Croatian
      Cres-breed sheep and ii) on small family goat farm. RESULTS: Sequence and
      phylogenetic analyses of the ORFV B2L gene showed that the Cro-Cres-12446/09 and
      Cro-Goat-11727/10 were not clustered together. Cro-Cres-12446/09 shared the
      highest similarity with ORFV NZ2 from New Zealand, and Ena from Japan; Cro-Goat
      11727/10 was closest to the HuB from China and Taiping and Hoping from Taiwan.
      CONCLUSION: Distinct ORFV strains are circulating in Croatia. Although ORFV
      infections are found ubiquitously wherever sheep and goats are farmed in Croatia,
      this is the first information on genetic relatedness of any Croatian ORFV with
      other isolates around the world.

PMID- 21073726
TI  - Early warnings of the potential for malaria transmission in rural Africa using
      the hydrology, entomology and malaria transmission simulator (HYDREMATS).
AB  - BACKGROUND: Early warnings of malaria transmission allow health officials to
      better prepare for future epidemics. Monitoring rainfall is recognized as an
      important part of malaria early warning systems. The Hydrology, Entomology and
      Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to
      malaria transmission, and could be used to provide early warnings of malaria
      epidemics. METHODS: HYDREMATS is used to make predictions of mosquito populations
      and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western
      Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall
      prediction based on the seasonal mean rainfall for a period two or four weeks
      into the future. RESULTS: Predictions made using this method provided reasonable
      estimates of mosquito populations and vectorial capacity, two to four weeks in
      advance. The predictions were significantly improved compared to those made when
      HYDREMATS was forced with seasonal mean rainfall alone. CONCLUSIONS: HYDREMATS
      can be used to make reasonable predictions of mosquito populations and vectorial
      capacity, and provide early warnings of the potential for malaria epidemics in
      Africa.

PMID- 21073727
TI  - The evaluation of a health education campaign on the use of leave from work
      during pregnancy.
AB  - BACKGROUND: The Italian Protective Maternity Legislation allows a woman to apply
      for early maternity leave from work during pregnancy if she is affected by health
      problems (option A) or if her working conditions are incompatible with pregnancy
      (option B). A community based health education program, implemented between 1995
      to 1998 in North Eastern Italy, provided counseling (by a team of gynecologists,
      pediatricians, geneticists, psychologists and occupational physicians), and an
      information leaflet detailing the risks during pregnancy and the governmental
      benefits available to expectant mothers. This leaflet was distributed to women
      who were under occupational medical surveillance and to women attending any
      healthcare office and outpatient department and was also mailed to women working
      at home as shoemakers.The effectiveness of this intervention has been evaluated
      in this investigation using an evidence based approach. METHODS: A quasi
      experimental design was adopted, applying several outcome measurements before
      (1989 to 1994) and after (1999 to 2005) the intervention. The outcome (ratio B/A)
      is the number of women receiving approval for B (circumstance where the pregnant
      woman is employed to undertake activities forbidden under the Article 7 of Law
      151/2001, and it is impossible to change her duties) to those receiving approval
      for A (risky pregnancy due to personal medical conditions, Article 17 of the same
      Law). A linear regression coefficient (for B/A against years) was obtained
      separately for time periods "before" (1989-94) and "after" (1999-2005) the
      intervention program. The two regression coefficients were compared using a t
      test. RESULTS: The trend over-time for the ratio B/A was steady before the
      initial intervention (y = 0.008x - 16.087; t = 2.09; p > 0.05) then increased
      considerably (y = 0.0426x - 84.89; t = 19.55; p < 0.001) in coincidence with the
      start of the education campaign. There was a significant difference between the
      two regression coefficients (t = 7.58; p < 0.001). CONCLUSION: From a
      bureaucratic perspective Option B is far more complicated than A. In fact it
      implies an active approach involving an arrangement between the claimant and the
      employer, who has to certify to the relevant Authority that the woman's working
      conditions are incompatible with pregnancy. The increasing number of women
      availing of option B, as recommended, therefore suggests the suitability of such
      educational campaign(s).

PMID- 21073728
TI  - Novel method of monitoring trace cytokines and activated STAT molecules in the
      paws of arthritic mice using multiplex bead technology.
AB  - BACKGROUND: The use of mouse models to study human disease provides useful data
      that can provide support for research projects or an existing drug discovery
      program. How well a model recapitulates the human condition and the ease and
      reproducibility of data collected will determine how much confidence a scientist
      can place on results obtained. Designing new treatments for rheumatic diseases,
      such as rheumatoid arthritis (RA), requires complex immunocompetent models that
      depend on intricate cytokine networks. Using local cytokines, signal transduction
      and transcription factor molecules as potential biomarkers to monitor disease and
      treatment efficacy is the best method to follow the progression of tissue damage
      and repair when testing an unknown compound or biologic. Described here in this
      report, a novel method for the non-enzymatic extraction and measurement of
      cytokines and signal transducers and activators of transcription (STAT) molecules
      using Luminex(r) bead array technology in two different mouse models for human RA
      -collagen antibody-dependent arthritis (CAIA) and collagen-induced arthritis
      (CIA). RESULTS: Dynamic expression of several pro-inflammatory cytokines
      responsible for promoting disease augmentation overtime were monitored, such as
      IL-1beta, TNFalpha, IL-6 and IL-12, locally in the paws of affected animals
      directly ex vivo. Local cytokine responses could be matched with serum cytokine
      levels and joint pathology results. In addition, STAT1, 3, and 5a/b activation
      status could be monitored with confidence using specifically formulated
      extraction buffer that protected the phosphorylation site. STAT3 activation
      followed paw swelling and cytokine levels in both models and correlates of
      disease could be ablated upon treatment with dexamethasone. Here reported a novel
      method of extracting joint fluid from the paws of inflamed mice coupled with
      powerful multiplex bead technology allowing us to measure cytokine responses,
      pharmacodynamic markers such as STATs and pharmacokinetic analysis of dosed agent
      all from the same sample directly ex vivo. CONCLUSIONS: This method is powerful
      in that it is applicable to multiple autoimmunity model types, streamlines ex
      vivo readouts in a high-throughput manner, and allows multiplexing providing the
      investigator with an array of options and possible analytes when developing
      preclinical animal models to support drug discovery efforts in the search for new
      treatments for rheumatic diseases.

PMID- 21073729
TI  - Proteome changes in platelets activated by arachidonic acid, collagen, and
      thrombin.
AB  - BACKGROUND: Platelets are small anucleated blood particles that play a key role
      in the control of bleeding. Platelets need to be activated to perform their
      functions and participate in hemostasis. The process of activation is accompanied
      by vast protein reorganization and posttranslational modifications. The goal of
      this study was to identify changes in proteins in platelets activated by
      different agonists. Platelets were activated by three different agonists -
      arachidonic acid, collagen, and thrombin. 2D SDS-PAGE (pI 4-7) was used to
      separate platelet proteins. Proteomes of activated and resting platelets were
      compared with each other by Progenesis SameSpots statistical software; and
      proteins were identified by nanoLC-MS/MS. RESULTS: 190 spots were found to be
      significantly different. Of these, 180 spots were successfully identified and
      correspond to 144 different proteins. Five proteins were found that had not
      previously been identified in platelets: protein CDV3 homolog, protein ETHE1,
      protein LZIC, FGFR1 oncogene partner 2, and guanine nucleotide-binding protein
      subunit beta-5. Using spot expression profile analysis, we found two proteins (WD
      repeat-containing protein 1 and mitochondrial glycerol-3-phosphate dehydrogenase)
      that may be part of thrombin specific activation or signal transduction
      pathway(s). CONCLUSIONS: Our results, characterizing the differences within
      proteins in both activated (by various agonists) and resting platelets, can thus
      contribute to the basic knowledge of platelets and to the understanding of the
      function and development of new antiplatelet drugs.

PMID- 21073730
TI  - Characterization of hepatitis B virus (HBV) genotypes in patients from Rondonia,
      Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) can be classified into nine genotypes (A-I)
      defined by sequence divergence of more than 8% based on the complete genome. This
      study aims to identify the genotypic distribution of HBV in 40 HBsAg-positive
      patients from Rondonia, Brazil. A fragment of 1306 bp partially comprising
      surface and polymerase overlapping genes was amplified by PCR. Amplified DNA was
      purified and sequenced. Amplified DNA was purified and sequenced on an ABI
      PRISM(r) 377 Automatic Sequencer (Applied Biosystems, Foster City, CA, USA). The
      obtained sequences were aligned with reference sequences obtained from the
      GenBank using Clustal X software and then edited with Se-Al software.
      Phylogenetic analyses were conducted by the Markov Chain Monte Carlo (MCMC)
      approach using BEAST v.1.5.3. RESULTS: The subgenotypes distribution was A1
      (37.1%), D3 (22.8%), F2a (20.0%), D4 (17.1%) and D2 (2.8%). CONCLUSIONS: These
      results for the first HBV genotypic characterization in Rondonia state are
      consistent with other studies in Brazil, showing the presence of several HBV
      genotypes that reflects the mixed origin of the population, involving descendants
      from Native Americans, Europeans, and Africans.

PMID- 21073731
TI  - Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of
      the gut microbiota.
AB  - BACKGROUND: Previous studies suggest a link between gut microbiota and the
      development of ulcerative colitis (UC) and irritable bowel syndrome (IBS). Our
      aim was to investigate any quantitative differences in faecal bacterial
      compositions in UC and IBS patients compared to healthy controls, and to identify
      individual bacterial species that contribute to these differences. METHODS:
      Faecal microbiota of 13 UC patients, 11 IBS patients and 22 healthy volunteers
      were analysed by PCR-Denaturing Gradient Gel Electrophoresis (DGGE) using
      universal and Bacteroides specific primers. The data obtained were normalized
      using in-house developed statistical method and interrogated by multivariate
      approaches. The differentiated bands were excised and identified by sequencing
      the V3 region of the 16S rRNA genes. RESULTS: Band profiles revealed that number
      of predominant faecal bacteria were significantly different between UC, IBS and
      control group (p < 10-4). By assessing the mean band numbers in UC (37 +/- 5) and
      IBS (39 +/- 6), compared to the controls (45 +/- 3), a significant decrease in
      bacterial species is suggested (p = 0.01). There were no significant differences
      between IBS and UC. Biodiversity of the bacterial species was significantly lower
      in UC (MU = 2.94, sigma = 0.29) and IBS patients (MU = 2.90, sigma = 0.38) than
      controls (MU = 3.25, sigma = 0.16; p = 0.01). Moreover, similarity indices
      revealed greater biological variability of predominant bacteria in UC and IBS
      compared to the controls (median Dice coefficients 76.1% (IQR 70.9 - 83.1), 73.8%
      (IQR 67.0 - 77.5) and 82.9% (IQR 79.1 - 86.7) respectively). DNA sequencing of
      discriminating bands suggest that the presence of Bacteroides vulgatus, B.
      ovatus, B. uniformis, and Parabacteroides sp. in healthy volunteers distinguishes
      them from IBS and UC patients. DGGE profiles of Bacteroides species revealed a
      decrease of Bacteroides community in UC relative to IBS and controls. CONCLUSION:
      Molecular profiling of faecal bacteria revealed abnormalities of intestinal
      microbiota in UC and IBS patients, while different patterns of Bacteroides
      species loss in particular, were associated with UC and IBS.

PMID- 21073733
TI  - Sharing best practices through online communities of practice: a case study.
AB  - INTRODUCTION: The USAID-funded Capacity Project established the Global Alliance
      for Pre-Service Education (GAPS) to provide an online forum to discuss issues
      related to teaching and acquiring competence in family planning, with a focus on
      developing countries' health related training institutions. The success of the
      Global Alliance for Nursing and Midwifery's ongoing web-based community of
      practice (CoP) provided a strong example of the successful use of this medium to
      reach many participants in a range of settings. CASE DESCRIPTION: GAPS functioned
      as a moderated set of forums that were analyzed by a small group of experts in
      family planning and pre-service education from three organizations. The cost of
      the program included the effort provided by the moderators and the time to
      administer responses and conduct the analysis. DISCUSSION AND EVALUATION: Family
      planning is still considered a minor topic in health related training
      institutions. Rather than focusing solely on family planning competencies, GAPS
      members suggested a focus on several professional competencies (e.g.
      communication, leadership, cultural sensitivity, teamwork and problem solving)
      that would enhance the resulting health care graduate's ability to operate in a
      complex health environment. Resources to support competency-based education in
      the academic setting must be sufficient and appropriately distributed. Where
      clinical competencies are incorporated into pre-service education, responsible
      faculty and preceptors must be clinically proficient. The interdisciplinary GAPS
      memberships allowed for a comparison and contrast of competencies, opportunities,
      promising practices, documents, lessons learned and key teaching strategies.
      CONCLUSIONS: Online CoPs are a useful interface for connecting developing country
      experiences. From CoPs, we may uncover challenges and opportunities that are
      faced in the absorption of key public health competencies required for decreasing
      maternal mortality and morbidity. Use of the World Health Organization (WHO)
      Implementing Best Practices Knowledge Gateway, which requires only a low
      bandwidth connection, gave educators an opportunity to engage in the discussion
      even in the most Internet access-restricted places (e.g. Ethiopia). In order to
      sustain an online CoP, funds must come from an international organization (e.g.
      WHO regional office) or university that can program the costs long-term.
      Eventually, the long-term effectiveness and sustainability of GAPS rests on its
      transfer to the members themselves.

PMID- 21073732
TI  - Curcumin activates the p38MPAK-HSP25 pathway in vitro but fails to attenuate
      diabetic nephropathy in DBA2J mice despite urinary clearance documented by HPLC.
AB  - BACKGROUND: Curcumin has anti-inflammatory, anti-oxidant, and anti-proliferative
      properties, and depending upon the experimental circumstances, may be pro- or
      anti-apoptotic. Many of these biological actions could ameliorate diabetic
      nephropathy. METHODS/DESIGN: Mouse podocytes, cultured in basal or high glucose
      conditions, underwent acute exposure to curcumin. Western blots for p38-MAPK, COX
      2 and cleaved caspase-3; isoelectric focusing for HSP25 phosphorylation; and
      DNase I assays for F- to G- actin cleavage were performed for in vitro analyses.
      In vivo studies examined the effects of dietary curcumin on the development of
      diabetic nephropathy in streptozotocin (Stz)-induced diabetes in DBA2J mice.
      Urinary albumin to creatinine ratios were obtained, high performance liquid
      chromatography was performed for urinary curcuminoid measurements, and Western
      blots for p38-MAPK and total HSP25 were performed. RESULTS: Curcumin enhanced the
      phosphorylation of both p38MAPK and downstream HSP25; inhibited COX-2; induced a
      trend towards attenuation of F- to G-actin cleavage; and dramatically inhibited
      the activation of caspase-3 in vitro. In curcumin-treated DBA2J mice with Stz
      diabetes, HPLC measurements confirmed the presence of urinary curcuminoid.
      Nevertheless, dietary provision of curcumin either before or after the induction
      of diabetes failed to attenuate albuminuria. CONCLUSIONS: Apart from species,
      strain, early differences in glycemic control, and/or dosing effects, the failure
      to modulate albuminuria may have been due to a decrement in renal HSP25 or
      stimulation of the 12/15 lipoxygenase pathway in DBA2J mice fed curcumin. In
      addition, these studies suggest that timed urine collections may be useful for
      monitoring curcumin dosing and renal pharmacodynamic effects.

PMID- 21073734
TI  - Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a
      randomized trial.
AB  - BACKGROUND: Elbow dislocations can be classified as simple or complex. Simple
      dislocations are characterized by the absence of fractures, while complex
      dislocations are associated with fractures. After reduction of a simple
      dislocation, treatment options include immobilization in a static plaster for
      different periods of time or so-called functional treatment. Functional treatment
      is characterized by early active motion within the limits of pain with or without
      the use of a sling or hinged brace. Theoretically, functional treatment should
      prevent stiffness without introducing increased joint instability. The primary
      aim of this randomized controlled trial is to compare early functional treatment
      versus plaster immobilization following simple dislocations of the elbow.
      METHODS/DESIGN: The design of the study will be a multicenter randomized
      controlled trial of 100 patients who have sustained a simple elbow dislocation.
      After reduction of the dislocation, patients are randomized between a pressure
      bandage for 5-7 days and early functional treatment or a plaster in 90 degrees
      flexion, neutral position for pro-supination for a period of three weeks. In the
      functional group, treatment is started with early active motion within the limits
      of pain. Function, pain, and radiographic recovery will be evaluated at regular
      intervals over the subsequent 12 months. The primary outcome measure is the Quick
      Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures
      are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both
      sides, range of motion of the elbow joint at both sides, rate of secondary
      interventions and complication rates in both groups (secondary dislocation,
      instability, relaxation), health-related quality of life (Short-Form 36 and
      EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and
      heterotopic ossifications), costs, and cost-effectiveness. DISCUSSION: The
      successful completion of this trial will provide evidence on the effectiveness of
      a functional treatment for the management of simple elbow dislocations. TRIAL
      REGISTRATION: The trial is registered at the Netherlands Trial Register
      (NTR2025).

PMID- 21073735
TI  - Construction of metabolically biotinylated adenovirus with deleted fiber knob as
      targeting vector.
AB  - Gene delivery vectors based on adenovirus, particularly human adenovirus serotype
      5 (hAd5) have great potential for the treatment of variety of diseases. However,
      the tropism of hAd5 needs to be modified to achieve tissue- or cell- specific
      therapies for the successful application of this vector system to clinic. Here,
      we modified hAd5 tropism by replacing the fiber knob which contains the
      coxsackievirus B and adenovirus receptor (CAR)-binding sites with a biotin
      acceptor peptide, a truncated form of Propionibacterium shermanii 1.3 S
      transcarboxylase domain (PSTCD), to enable metabolically biotinylation of the
      virus. We demonstrate here that the new adenovirus no longer shows CAR-dependent
      cell uptake and transduction. When metabolically biotinylated and avidin-coated,
      it forms a nano-complex that can be retargeted to distinct cells using
      biotinylated antibodies. This vector may prove useful in the path towards
      achieving targeted gene delivery.

PMID- 21073736
TI  - Quantification and deconvolution of asymmetric LC-MS peaks using the bi-Gaussian
      mixture model and statistical model selection.
AB  - BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS) is one of the major
      techniques for the quantification of metabolites in complex biological samples.
      Peak modeling is one of the key components in LC-MS data pre-processing. RESULTS:
      To quantify asymmetric peaks with high noise level, we developed an estimation
      procedure using the bi-Gaussian function. In addition, to accurately quantify
      partially overlapping peaks, we developed a deconvolution method using the bi
      Gaussian mixture model combined with statistical model selection. CONCLUSIONS:
      Using extensive simulations and real data, we demonstrated the advantage of the
      bi-Gaussian mixture model over the Gaussian mixture model and the method of
      kernel smoothing combined with signal summation in peak quantification and
      deconvolution. The method is implemented in the R package apLCMS:
      http://www.sph.emory.edu/apLCMS/.

PMID- 21073737
TI  - Oncogenic KRAS modulates mitochondrial metabolism in human colon cancer cells by
      inducing HIF-1alpha and HIF-2alpha target genes.
AB  - BACKGROUND: Activating KRAS mutations are important for cancer initiation and
      progression; and have recently been shown to cause primary resistance to
      therapies targeting the epidermal growth factor receptor. Therefore, strategies
      are currently in development to overcome treatment resistance due to oncogenic
      KRAS. The hypoxia-inducible factors-1alpha and -2alpha (HIF-1alpha and HIF
      2alpha) are activated in cancer due to dysregulated ras signaling. METHODS: To
      understand the individual and combined roles of HIF-1alpha and HIF-2alpha in
      cancer metabolism and oncogenic KRAS signaling, we used targeted homologous
      recombination to disrupt the oncogenic KRAS, HIF-1alpha, and HIF-2alpha gene loci
      in HCT116 colon cancer cells to generate isogenic HCT116WT KRAS, HCT116HIF-1alpha
      /-, HCT116HIF-2alpha-/-, and HCT116HIF-1alpha-/-HIF-2alpha-/- cell lines.
      RESULTS: Global gene expression analyses of these cell lines reveal that HIF
      1alpha and HIF-2alpha work together to modulate cancer metabolism and regulate
      genes signature overlapping with oncogenic KRAS. Cancer cells with disruption of
      both HIF-1alpha and HIF-2alpha or oncogenic KRAS showed decreased aerobic
      respiration and ATP production, with increased ROS generation. CONCLUSION: Our
      findings suggest novel strategies for treating tumors with oncogenic KRAS
      mutations.

PMID- 21073738
TI  - WEB downloadable software for training in cardiovascular hemodynamics in the (3
      D) stress echo lab.
AB  - When a physiological (exercise) stress echo is scheduled, interest focuses on
      wall motion segmental contraction abnormalities to diagnose ischemic response to
      stress, and on left ventricular ejection fraction to assess contractile reserve.
      Echocardiographic evaluation of volumes (plus standard assessment of heart rate
      and blood pressure) is ideally suited for the quantitative and accurate
      calculation of a set of parameters allowing a complete characterization of
      cardiovascular hemodynamics (including cardiac output and systemic vascular
      resistance), left ventricular elastance (mirroring left ventricular
      contractility, theoretically independent of preload and afterload changes heavily
      affecting the ejection fraction), arterial elastance, ventricular arterial
      coupling (a central determinant of net cardiovascular performance in normal and
      pathological conditions), and diastolic function (through the diastolic mean
      filling rate). All these parameters were previously inaccessible, inaccurate or
      labor-intensive and now become, at least in principle, available in the stress
      echocardiography laboratory since all of them need an accurate estimation of left
      ventricular volumes and stroke volume, easily derived from 3 D echo. Aims of this
      paper are: 1) to propose a simple method to assess a set of parameters allowing a
      complete characterization of cardiovascular hemodynamics in the stress echo lab,
      from basic measurements to calculations 2) to propose a simple, web-based
      software program, to learn and training calculations as a phantom of the everyday
      activity in the busy stress echo lab 3) to show examples of software testing in a
      way that proves its value.The informatics infrastructure is available on the web,
      linking to http://cctrainer.ifc.cnr.it.

PMID- 21073739
TI  - Temporal reliability of cytokines and growth factors in EDTA plasma.
AB  - BACKGROUND: Cytokines are involved in the development of chronic diseases,
      including cancer. It is important to evaluate the temporal reproducibility of
      cytokines in plasma prior to conducting epidemiologic studies utilizing these
      markers. FINDINGS: We assessed the temporal reliability of CRP, 22 cytokines and
      their soluble receptors (IL-1alpha, IL-1beta, IL-1RA, IL-2, sIL-2R, IL-4, IL-5,
      IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17,
      TNFalpha, sTNF-R1, sTNF-R2, IFNalpha, IFNgamma) and eight growth factors (GM-CSF,
      EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples
      collected an average of two years apart from 18 healthy women (age range: 42-62)
      enrolled in a prospective cohort study. We also estimated the correlation between
      serum and plasma biomarker levels using 18 paired clinical samples from
      postmenopausal women (age range: 75-86).Twenty-six assays were able to detect
      their analytes in at least 70% of samples. Of those 26 assays, we observed
      moderate to high intra-class correlation coefficients (ICCs)(ranging from 0.53
      0.89) for 22 assays, and low ICCs (0-0.47) for four assays. Serum and plasma
      levels were highly correlated (r > 0.6) for most markers, except for seven assays
      (r < 0.5). CONCLUSIONS: For 22 of the 31 biomarkers, a single plasma measurement
      is a reliable estimate of a woman's average level over a two-year period.

PMID- 21073740
TI  - Bioprocess control in microscale: scalable fermentations in disposable and user
      friendly microfluidic systems.
AB  - BACKGROUND: The efficiency of biotechnological production processes depends on
      selecting the best performing microbial strain and the optimal cultivation
      conditions. Thus, many experiments have to be conducted, which conflicts with the
      demand to speed up drug development processes. Consequently, there is a great
      need for high-throughput devices that allow rapid and reliable bioprocess
      development. This need is addressed, for example, by the fiber-optic online
      monitoring system BioLector which utilizes the wells of shaken microtiter plates
      (MTPs) as small-scale fermenters. To further improve the application of MTPs as
      microbioreactors, in this paper, the BioLector technology is combined with
      microfluidic bioprocess control in MTPs. To realize a user-friendly system for
      routine laboratory work, disposable microfluidic MTPs are utilized which are
      actuated by a user-friendly pneumatic hardware. RESULTS: This novel
      microfermentation system was tested in pH-controlled batch as well as in fed
      batch fermentations of Escherichia coli. The pH-value in the culture broth could
      be kept in a narrow dead band of 0.03 around the pH-setpoint, by pneumatically
      dosing ammonia solution and phosphoric acid to each culture well. Furthermore,
      fed-batch cultivations with linear and exponential feeding of 500 g/L glucose
      solution were conducted. Finally, the scale-up potential of the microscale
      fermentations was evaluated by comparing the obtained results to that of fully
      controlled fermentations in a 2 L laboratory-scale fermenter (working volume of 1
      L). The scale-up was realized by keeping the volumetric mass transfer coefficient
      kLa constant at a value of 460 1/h. The same growth behavior of the E. coli
      cultures could be observed on both scales. CONCLUSION: In microfluidic MTPs, pH
      controlled batch as well as fed-batch fermentations were successfully performed.
      The liquid dosing as well as the biomass growth kinetics of the process
      controlled fermentations agreed well both in the microscale and laboratory scale.
      In conclusion, a user-friendly and disposable microfluidic system could be
      established which allows scaleable, fully controlled and fully monitored
      fermentations in working volumes below 1 milliliter.

PMID- 21073741
TI  - Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk
      between mitochondrial impairments, alpha synuclein aggregation, oxidative damage
      and behavioral changes.
AB  - BACKGROUND: In recent years, several lines of evidence have shown an increase in
      Parkinson's disease prevalence in rural environments where pesticides are heavily
      used. Although, the underlying mechanism for neuronal degeneration in sporadic PD
      remains unknown, mitochondrial dysfunction, oxidative stress and proteasomal
      dysfunction are proposed as contributing factors. In this study rats were
      chronically and continuously exposed to the pesticide, dichlorvos to identify the
      molecular mechanism of nigrostaital neuronal degeneration. RESULT: Chronic
      dichlorvos exposure (2.50 mg/kg b.wt.s.c/daily for 12 weeks) caused nigrostriatal
      dopaminergic degeneration. The degenerative changes were accompanied by a loss of
      60-80% of the nigral dopamine neurons and 60-70% reduction in striatal dopamine
      and tyrosine hydroxylase levels. Dichlorvos exposed animals also showed alpha 
      synuclein and ubiquitin positive inclusions along with swollen, dystrophic
      neurites and mitochondrial abnormalities like decreased complex I&IV activities,
      increased mitochondrial size, axonal degeneration and presence of electron dense
      perinuclear cytoplasmic inclusions in the substantia nigra of rats. These animals
      also showed evidence of oxidative stress, including increased mitochondrial ROS
      levels, decreased MnSOD activity and increased lipid peroxidation. Measurable
      impairments in neurobehavioral indices were also observed. Notable exacerbations
      in motor impairments, open field and catalepsy were also evident in dichlorvos
      exposed animals. CONCLUSION: All these findings taken together indicate that
      chronic dichlorvos exposure may cause nigrostaital neurodegenaration and
      significant behavioral impairments.

PMID- 21073742
TI  - Identification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a binding
      protein for a 68-kDa Bacillus thuringiensis parasporal protein cytotoxic against
      leukaemic cells.
AB  - BACKGROUND: Bacillus thuringiensis (Bt), an ubiquitous gram-positive spore
      forming bacterium forms parasporal proteins during the stationary phase of its
      growth. Recent findings of selective human cancer cell-killing activity in non
      insecticidal Bt isolates resulted in a new category of Bt parasporal protein
      called parasporin. However, little is known about the receptor molecules that
      bind parasporins and the mechanism of anti-cancer activity. A Malaysian Bt
      isolate, designated Bt18 produces parasporal protein that exhibit preferential
      cytotoxic activity for human leukaemic T cells (CEM-SS) but is non-cytotoxic to
      normal T cells or other cancer cell lines such as human cervical cancer (HeLa),
      human breast cancer (MCF-7) and colon cancer (HT-29) suggesting properties
      similar to parasporin. In this study we aim to identify the binding protein for
      Bt18 in human leukaemic T cells. METHODS: Bt18 parasporal protein was separated
      using Mono Q anion exchange column attached to a HPLC system and antibody was
      raised against the purified 68-kDa parasporal protein. Receptor binding assay was
      used to detect the binding protein for Bt18 parasporal protein in CEM-SS cells
      and the identified protein was sent for N-terminal sequencing. NCBI protein BLAST
      was used to analyse the protein sequence. Double immunofluorescence staining
      techniques was applied to localise Bt18 and binding protein on CEM-SS cell.
      RESULTS: Anion exchange separation of Bt18 parasporal protein yielded a 68-kDa
      parasporal protein with specific cytotoxic activity. Polyclonal IgG (anti-Bt18)
      for the 68-kDa parasporal protein was successfully raised and purified. Receptor
      binding assay showed that Bt18 parasporal protein bound to a 36-kDa protein from
      the CEM-SS cells lysate. N-terminal amino acid sequence of the 36-kDa protein was
      GKVKVGVNGFGRIGG. NCBI protein BLAST revealed that the binding protein was
      Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Double immunofluorescence
      staining showed co-localisation of Bt18 and GAPDH on the plasma membrane of the
      CEM-SS cells. CONCLUSIONS: GAPDH has been well known as a glycolytic enzyme, but
      recently GAPDH was discovered to have roles in apoptosis and carcinogenesis. Pre
      incubation of anti-GAPDH antibody with CEM-SS cells decreases binding of Bt18 to
      the susceptible cells. Based on a qualitative analysis of the immunoblot and
      immunofluorescence results, GAPDH was identified as a binding protein on the
      plasma membrane of CEM-SS cells for Bt18 parasporal protein.

PMID- 21073743
TI  - Epidemiological manifestations of hepatitis C virus genotypes and its association
      with potential risk factors among Libyan patients.
AB  - BACKGROUND: The information on hepatitis C virus genotypes and subtypes among
      Libyan population and its association with various risk factors is not known. The
      objectives of this study were to determine the epidemiological manifestations of
      HCV genotypes among Libyan patients and their association with certain potential
      risk factors. METHODS: A total of 1240 of HCV infected patients registered at
      Tripoli Medical Centre were studied in five years period from January 2005 to
      October 2009. The information were reviewed and the data were collected. A sample
      from each patient (785 male; 455 female) was analysed for genotyping and sub
      typing using specific genotyping assay. The information was correlated with the
      risk factors studied and the statistical data were analyzed using SPSS version
      11.5. RESULTS: Off the total patients studied, four different genotypes were
      reported, including genotypes 1, 2, 3, and 4. Genotype4 was the commonest
      (35.7%), followed by genotype1 (32.6%). According to subtypes 28% were
      unclassified genotype 4, 14.6% were genotype 1b and some patients infected with
      more than one subtype (2.3% genotype 4c/d, 1% genotype 2a/c). Genotypes 1 was the
      commonest among males, while genotype 4 among females. According to the risk
      factors studied, Genotype1 and genotype 4 were found with most of the risk
      factors. Though they were particularly evident surgical intervention, dental
      procedures and blood transfusion while genotype 1 was only followed by genotype 3
      mainly which mainly associated with certain risk groups such as intravenous drug
      abusers. CONCLUSION: Here in we report on a detailed description of HCV genotype
      among Libyans. The most common genotype was type 4 followed by genotype 1, other
      genotypes were also reported at a low rate. The distribution of such genotypes
      were also variable according to gender and age. The commonly prevalent genotypes
      found to be attributable to the medical -related transmission of HCV, such as
      blood, surgery and dental procedures when compared with other risk factors. This
      however, raises an alarming signal on the major steps to be taken to reduce such
      infection in Libya.

PMID- 21073744
TI  - Interactive seminars or small group tutorials in preclinical medical education:
      results of a randomized controlled trial.
AB  - BACKGROUND: Learning in small group tutorials is appreciated by students and
      effective in the acquisition of clinical problem-solving skills but poses
      financial and resource challenges. Interactive seminars, which accommodate large
      groups, might be an alternative. This study examines the educational
      effectiveness of small group tutorials and interactive seminars and students'
      preferences for and satisfaction with these formats. METHODS: Students in year
      three of the Leiden undergraduate medical curriculum, who agreed to participate
      in a randomized controlled trial (RCT, n = 107), were randomly allocated to small
      group tutorials (n = 53) or interactive seminars (n = 54). Students who did not
      agree were free to choose either format (n = 105). Educational effectiveness was
      measured by comparing the participants' results on the end-of-block test. Data on
      students' reasons and satisfaction were collected by means of questionnaires.
      Data was analyzed using student unpaired t test or chi-square test where
      appropriate. RESULTS: There were no significant differences between the two
      educational formats in students' test grades. Retention of knowledge through
      active participation was the most frequently cited reason for preferring small
      group tutorials, while a dislike of compulsory course components was mentioned
      more frequently by students preferring interactive seminars. Small group
      tutorials led to greater satisfaction. CONCLUSIONS: We found that small group
      tutorials leads to greater satisfaction but not to better learning results.
      Interactive learning in large groups might be might be an effective alternative
      to small group tutorials in some cases and be offered as an option.

PMID- 21073745
TI  - Inhibition of core gene of HCV 3a genotype using synthetic and vector derived
      siRNAs.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major causative agent of liver
      associated diseases throughout the world, with genotype 3a responsible for most
      of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA
      interference (RNAi) a novel regulatory and powerful silencing approach for
      molecular therapeutics through a sequence-specific RNA degradation process
      represents an alternative option. RESULTS: The current study was purposed to
      assess and explore the possibility of RNAi to silence the HCV-3a Core gene
      expression, which play complex role in regulation of cell growth and host genes
      expression essential for infectivity and disease progression. To identify the
      potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene
      were designed and in vitro transcribed after consensus sequence analysis of
      different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition
      of Core gene expression by different siRNAs into Huh-7 cells as compared with
      Mock transfected and control siRNAs treated cells. For long lasting effect of
      siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested
      against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and
      protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of
      cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV
      replication in HCV infected serum inoculated Huh-7 cells and a significant
      decrease in HCV viral copy number was observed. CONCLUSIONS: Our results support
      the possibility of using consensus siRNA and shRNA-based molecular therapy as a
      promising strategy in effective inhibition of HCV-3a genotype.

PMID- 21073747
TI  - NetMHCIIpan-2.0 - Improved pan-specific HLA-DR predictions using a novel
      concurrent alignment and weight optimization training procedure.
AB  - BACKGROUND: Binding of peptides to Major Histocompatibility class II (MHC-II)
      molecules play a central role in governing responses of the adaptive immune
      system. MHC-II molecules sample peptides from the extracellular space allowing
      the immune system to detect the presence of foreign microbes from this
      compartment. Predicting which peptides bind to an MHC-II molecule is therefore of
      pivotal importance for understanding the immune response and its effect on host
      pathogen interactions. The experimental cost associated with characterizing the
      binding motif of an MHC-II molecule is significant and large efforts have
      therefore been placed in developing accurate computer methods capable of
      predicting this binding event. Prediction of peptide binding to MHC-II is
      complicated by the open binding cleft of the MHC-II molecule, allowing binding of
      peptides extending out of the binding groove. Moreover, the genes encoding the
      MHC molecules are immensely diverse leading to a large set of different MHC
      molecules each potentially binding a unique set of peptides. Characterizing each
      MHC-II molecule using peptide-screening binding assays is hence not a viable
      option. RESULTS: Here, we present an MHC-II binding prediction algorithm aiming
      at dealing with these challenges. The method is a pan-specific version of the
      earlier published allele-specific NN-align algorithm and does not require any pre
      alignment of the input data. This allows the method to benefit also from
      information from alleles covered by limited binding data. The method is evaluated
      on a large and diverse set of benchmark data, and is shown to significantly out
      perform state-of-the-art MHC-II prediction methods. In particular, the method is
      found to boost the performance for alleles characterized by limited binding data
      where conventional allele-specific methods tend to achieve poor prediction
      accuracy. CONCLUSIONS: The method thus shows great potential for efficient
      boosting the accuracy of MHC-II binding prediction, as accurate predictions can
      be obtained for novel alleles at highly reduced experimental costs. Pan-specific
      binding predictions can be obtained for all alleles with know protein sequence
      and the method can benefit by including data in the training from alleles even
      where only few binders are known. The method and benchmark data are available at
      http://www.cbs.dtu.dk/services/NetMHCIIpan-2.0.

PMID- 21073746
TI  - The membrane-spanning domain of gp41 plays a critical role in intracellular
      trafficking of the HIV envelope protein.
AB  - BACKGROUND: The sequences of membrane-spanning domains (MSDs) on the gp41 subunit
      are highly conserved among many isolates of HIV-1. The GXXXG motif, a potential
      helix-helix interaction motif, and an arginine residue (rare in hydrophobic MSDs)
      are especially well conserved. These two conserved elements are expected to
      locate on the opposite sides of the MSD, if the MSD takes a alpha-helical
      secondary structure. A scanning alanine-insertion mutagenesis was performed to
      elucidate the structure-function relationship of gp41 MSD. RESULTS: A circular
      dichroism analysis of a synthetic gp41 MSD peptide determined that the secondary
      structure of the gp41 MSD was alpha-helical. We then performed a scanning alanine
      insertion mutagenesis of the entire gp41 MSD, progressively shifting the relative
      positions of MSD segments around the helix axis. Altering the position of Gly694,
      the last residue of the GXXXG motif, relative to Arg696 (the number indicates the
      position of the amino acid residues in HXB2 Env) around the axis resulted in
      defective fusion. These mutants showed impaired processing of the gp160 precursor
      into gp120 and gp41. Furthermore, these Env mutants manifested inefficient
      intracellular transport in the endoplasmic reticulum and Golgi regions. Indeed, a
      transplantation of the gp41 MSD portion into the transmembrane domain of another
      membrane protein, Tac, altered its intracellular distribution. Our data suggest
      that the intact MSD alpha-helix is critical in the intracellular trafficking of
      HIV-1 Env. CONCLUSIONS: The relative position between the highly conserved GXXXG
      motif and an arginine residue around the gp41 MSD alpha-helix is critical for
      intracellular trafficking of HIV-1 Env. The gp41 MSD region not only modulates
      membrane fusion but also controls biosynthesis of HIV-1 Env.

PMID- 21073748
TI  - Identification of amino acid residues in protein SRP72 required for binding to a
      kinked 5e motif of the human signal recognition particle RNA.
AB  - BACKGROUND: Human cells depend critically on the signal recognition particle
      (SRP) for the sorting and delivery of their proteins. The SRP is a
      ribonucleoprotein complex which binds to signal sequences of secretory
      polypeptides as they emerge from the ribosome. Among the six proteins of the
      eukaryotic SRP, the largest protein, SRP72, is essential for protein targeting
      and possesses a poorly characterized RNA binding domain. RESULTS: We delineated
      the minimal region of SRP72 capable of forming a stable complex with an SRP RNA
      fragment. The region encompassed residues 545 to 585 of the full-length human
      SRP72 and contained a lysine-rich cluster (KKKKKKKKGK) at postions 552 to 561 as
      well as a conserved Pfam motif with the sequence PDPXRWLPXXER at positions 572 to
      583. We demonstrated by site-directed mutagenesis that both regions participated
      in the formation of a complex with the RNA. In agreement with biochemical data
      and results from chymotryptic digestion experiments, molecular modeling of SRP72
      implied that the invariant W577 was located inside the predicted structure of an
      RNA binding domain. The 11-nucleotide 5e motif contained within the SRP RNA
      fragment was shown by comparative electrophoresis on native polyacrylamide gels
      to conform to an RNA kink-turn. The model of the complex suggested that the
      conserved A240 of the K-turn, previously identified as being essential for the
      binding to SRP72, could protrude into a groove of the SRP72 RNA binding domain,
      similar but not identical to how other K-turn recognizing proteins interact with
      RNA. CONCLUSIONS: The results from the presented experiments provided insights
      into the molecular details of a functionally important and structurally
      interesting RNA-protein interaction. A model for how a ligand binding pocket of
      SRP72 can accommodate a new RNA K-turn in the 5e region of the eukaryotic SRP RNA
      is proposed.

PMID- 21073749
TI  - The effect of combination therapy of allicin and fenofibrate on high fat diet
      induced vascular endothelium dysfunction and liver damage in rats.
AB  - BACKGROUND: It is designed to investigate the effects of combination therapy of
      allicin and fenofibrate on the endothelial and liver functions in rats with
      hyperlipidemia. METHODS: The healthy male Wistar rats fed high fat diet were
      treated with fenofibrate (80 mg/kg per day) alone, allicin (60 mg/kg per day)
      alone and a lower dosage of combined therapy (allicin 20 mg/kg per day and
      fenofibrate 30 mg/kg per day) respectively for 8 weeks. The serum levels of
      cholesterol, triglyceride, nitrogen oxidative, alanine transferase (ALT) and
      aspartate transferase (AST) were determined. Acetylcholine-induced endothelium
      dependent vascular relaxation (EDVR) of aorta rings was tested, and the
      morphologic changes of liver tissue were observed. RESULTS: Compared with high
      fat diet control, fenofibrate alone or the combined therapy increased remarkably
      the levels of high density lipoprotein respectively (P<0.05). Both single and
      combined therapy of fenofibrate and allicin significantly enhanced the levels of
      NO (P<0.01 or P<0.05), but the combined therapy had greatest high EDVR responses
      (P<0.01). Furthermore, the reduced levels of ALT and AST were significantly
      obvious in the combined therapy groups (P<0.01 or P<0.05). In addition, the lower
      dosage of combined therapy significantly ameliorated severe fatty degeneration of
      liver cells occurred in the high fat diet fed rat although the single fenofibrate
      treatment showed spotty necrosis of liver cells and bile duct expansion.
      CONCLUSION: Combination therapy with allicin and fenofibrate can effectively
      enhance the protective effects on endothelial function and reduce the hepatic
      damage in rats with hyperlipidemia.

PMID- 21073750
TI  - Laparoscopic adjustable banded roux-en-y gastric bypass as a primary procedure
      for the super-super-obese (body mass index > 60 kg/m2).
AB  - BACKGROUND: Currently, there is no consensus opinion regarding the optimal
      procedure of choice in super-super-morbid obesity (Body mass index, BMI > 60
      kg/m2). Roux-en-Y gastric bypass (RYGB) is associated with failure to achieve or
      maintain 50% excess weight loss (EWL) or BMI < 35 in approximately 15% of
      patients. Also, percent EWL is significantly less after 1-year in the super-super
      obese group as compared with the less obese group and many patients are still
      technically considered to be obese (lowest post-surgical BMI > 35) following RYGB
      surgery in this group. The addition of adjustable gastric band (AGB) to RYGB has
      been reported as a revisional procedure but this combined bariatric procedure has
      not been explored as a primary operation. METHODS: In a primary laparoscopic
      RYGB, an AGB is drawn around the gastric pouch through a small opening between
      the blood vessels on the lesser curve and the gastric pouch. The band is then
      fixed by suturing the gastric remnant to the gastric pouch both above and below
      the band to prevent slippage. RESULTS: Between November 2009 and March 2010, 6
      consecutive super-super-obese patients underwent a primary laparoscopic
      adjustable banded Roux-en-Y gastric bypass procedure at our institution. One male
      patient (21 years, BMI 70 kg/m2) developed a pneumonia postoperatively. No other
      postoperative complications were observed. CONCLUSION: To the best of our
      knowledge, this is the first series of patients that underwent a laparoscopic
      adjustable banded RYGB as a primary operation for the super-super obese in the
      indexed literature. With the combined procedure, a sequential action mechanism
      for weight loss is to be expected. The restrictive, malabsorptive and hormonal
      working mechanism of the RYGB will induce weight loss from the start reaching a
      stabilised plateau of weight after 12 - 18 months. At that time, filling of the
      band can be started resulting in further gastric pouch restriction and increased
      weight loss. Moreover, besides improving the results of total weight loss, a
      gradual filling of the band can as well prevent the RYGB patient from weight
      regain if restriction would fade away with time.

PMID- 21073751
TI  - Transitional cell carcinoma of the ovary: a rare case and review of literature.
AB  - INTRODUCTION: Transitional cell carcinoma (TCC) of the ovary is a rare, recently
      recognized, subtype of ovarian surface epithelial cancer. CASE PRESENTATION: A 69
      year-old postmenopausal woman presented with a 2-year history of progressive
      enlargement of an abdominal mass. Abdominal computed tomography showed a pelvic
      mass. CA-125 was normal. A staging operation with total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, infracolic omentectomy and pelvic lymph node
      dissection was performed. After surgery, the pathologic report of the right
      ovarian tumour was TCC, grade 3, stage IC. The patient underwent 3 cycles of
      chemotherapy: carboplatin and paclitaxel. She is regularly followed up and has
      been disease free for 10 months CONCLUSION: Transitional cell carcinoma (TCC) of
      the ovary is a rare subtype of epithelial ovarian cancer. Surgical resection is
      the primary therapeutic approach, and patient outcomes after chemotherapy are
      better than for other types of ovarian cancers.

PMID- 21073752
TI  - An unusual case of left ventricular aneurysm in duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) leads to structural heart disease, including
      dilated cardiomyopathy, in 90% of patients >18 years of age. Despite the ubiquity
      of cardiomyopathy associated with DMD, ventricular aneurysms in these patients
      have rarely been reported. We present a case of a basal inferoposterior aneurysm
      of the left ventricle in a 23-year-old male patient with DMD.

PMID- 21073753
TI  - The complexity of premenstrual dysphoric disorder--risk factors in the population
      of Polish women.
AB  - BACKGROUND: Premenstrual dysphoric disorder has multiple determinants in the
      biological, psychological and socio-cultural domains. The aim of the study was to
      evaluate the risk factors for premenstrual dysphoric disorder in Polish women,
      considering their reproductive history, socio-economic factors, as well as
      lifestyle and health-related factors. METHODS: 2,500 females, aged 18 to 45, from
      the Upper Silesian region of Poland were eligible for the prospective population
      study. The final study sample was 1,540 individuals. The research was based on a
      questionnaire containing socio-economic status, general health, lifestyle,
      medical and reproductive history, premenstrual symptoms based on the American
      Psychiatric Association's criteria for diagnosing premenstrual dysphoric
      disorder, and patient prospective daily ratings of symptoms. The Statistica 8.0
      computer software was used for statistical analysis. The value of p < 0.05 was
      adopted as the level of statistical significance. RESULTS: The mean age of the
      studied population was 31.9 +/- 7.3 years. The majority of the studied women were
      married (57.9%), lived in large cities (42.0%) and had tertiary education
      (43.2%). The results of the study indicated that the prevalence of premenstrual
      dysphoric disorder was 2.1%. The final statistical analysis revealed that only
      tertiary education decreased the risk of premenstrual dysphoric disorder (OR =
      0.08; p < 0.05). CONCLUSIONS: Our research showed that women with tertiary
      education are less vulnerable to premenstrual dysphoric disorder than women with
      a lower level of education. Reproductive and lifestyle factors seem to be play a
      lesser role.

PMID- 21073754
TI  - Demonstration of the histopathological and immunohistochemical effects of a novel
      hemostatic agent, Ankaferd Blood Stopper, on vascular tissue in a rat aortic
      bleeding model.
AB  - BACKGROUND: Ankaferd Blood Stopper(r) (ABS) is a folkloric medicinal plant
      extract used as a hemostatic agent in traditional Turkish medicine. This
      experimental study investigated the histopathological and immunohistochemical
      effects of ABS on vascular tissue in a rat model of aortic bleeding. METHODS:
      Four groups of 11 Wistar albino rats were used. The abdominal aortas of the rats
      were wounded; an ABS-soaked tampon was applied to rats in Groups 1 and 3, and a
      plain gauze tampon was applied to rats in Groups 2 and 4 until the bleeding
      stopped. The bleeding time was recorded. Immediately following sacrificing, the
      arteriotomy sites from Groups 1 and 2 were removed. The abdominal incisions in
      Groups 3 and 4 were closed following hemostasis. On Day 7 of the study, Group 3
      and 4 rats were sacrificed and the abdominal aorta arteriotomy sites were removed
      for histopathological and immunohistochemical evaluation. RESULTS: The mean
      bleeding time in 15 animals in Groups 2 and 4 was 4.9 +/- 0.6 s, and in 22
      animals in Groups 1 and 3 was 3.1 +/- 0.6 s. Distal aortic occlusion was not
      observed on either Day 1 or 7 in any group. Significantly more widespread and
      dense endothelial nitric oxide synthase (eNOS) staining was observed in Group 1
      animals than Group 2. On Days 1 and 7 after application of ABS, histopathological
      changes, consisting of necrosis, inflammation, and endothelial cell loss, in the
      rat abdominal aortas did not differ between Groups 1 and 2. The basophilic
      discoloration in the ABS group on the operation day was a result of a foreign
      body reaction and hemosiderin-loaded histiocyte accumulation, which occurred on
      Day 7. CONCLUSIONS: In this study, hemostasis was successfully achieved with ABS
      in rat abdominal aortas. No histopathological change was found in the rat
      abdominal aortas between the ABS and control groups on Days 1 and 7. Further
      studies on the long-term effects of foreign body reactions and hemosiderin-loaded
      histiocyte accumulation are required.

PMID- 21073755
TI  - Prevalence and acquisition of MRSA amongst patients admitted to a tertiary-care
      hospital in Brazil.
AB  - BACKGROUND: There are few studies in Brazil that address baseline prevalence of
      MRSA colonization and associated risk factors at hospital admission, or the
      incidence of nosocomial colonization. We report a prospective study in a tertiary
      care, university-affiliated hospital to implement a new MRSA control policy at
      the institution. METHODS: A cohort of randomly selected patients admitted to
      emergency and clinical wards at our hospital was followed until discharge. Nasal
      swabs were taken for identification of MRSA-colonized patients and detection of
      SCCmecA in positive cultures, at admission and weekly thereafter. Multivariate
      analysis using a log-binomial analysis was used to identify risk factors for
      colonization. RESULTS: After screening 297 adult patients and 176 pediatric
      patients, the prevalence of MRSA at admission was 6.1% (95%CI, 3.6% to 9.4%), in
      the adult population and 2.3% (95%CI, 0.6% to 5.7%), for children. From
      multivariate analysis, the risk factors associated with colonization in adults
      were: age above 60 years (P = 0.019) and hospitalization in the previous year (P
      = 0.022). Incidence analysis was performed in 276 MRSA-negative patients (175
      adults and 101 children). Acquisition rate was 5.5/1,000 patient-days for adults
      (95%CI, 3.4 to 8.5/1,000 patients-days), and 1.1/1,000 patient-days for children
      (95%CI, 0.1 to 4.0/1,000 patients-days). CONCLUSIONS: The identification of MRSA
      carriers is a step towards establishing a control policy for MRSA, and helps to
      identify measures needed to reduce colonization pressure and to decrease the high
      acquisition rate in hospitalized patients.

PMID- 21073756
TI  - Stage-specific fluorescence intensity of GFP and mCherry during sporulation In
      Bacillus Subtilis.
AB  - BACKGROUND: Fluorescent proteins are powerful molecular biology tools that have
      been used to study the subcellular dynamics of proteins within live cells for
      well over a decade. Two fluorescent proteins commonly used to enable dual protein
      labelling are GFP (green) and mCherry (red). Sporulation in the Gram positive
      bacterium Bacillus subtilis has been studied for many years as a paradigm for
      understanding the molecular basis for differential gene expression. As
      sporulation initiates, cells undergo an asymmetric division leading to
      differential gene expression in the small prespore and large mother cell
      compartments. Use of two fluorescent protein reporters permits time resolved
      examination of differential gene expression either in the same compartments or
      between compartments. Due to the spectral properties of GFP and mCherry, they are
      considered an ideal combination for co-localisation and co-expression
      experiments. They can also be used in combination with fluorescent DNA stains
      such as DAPI to correlate protein localisation patterns with the developmental
      stage of sporulation which can be linked to well characterised changes in DNA
      staining patterns. FINDINGS: While observing the recruitment of the transcription
      machinery into the forespore of sporulating Bacillus subtilis, we noticed the
      occurrence of stage-specific fluorescence intensity differences between GFP and
      mCherry. During vegetative growth and the initial stages of sporulation,
      fluorescence from both GFP and mCherry fusions behaved similarly. During stage II
      III of sporulation we found that mCherry fluorescence was considerably
      diminished, whilst GFP signals remained clearly visible. This fluorescence
      pattern reversed during the final stage of sporulation with strong mCherry and
      low GFP fluorescence. These trends were observed in reciprocal tagging
      experiments indicating a direct effect of sporulation on fluorescent protein
      fluorophores. CONCLUSIONS: Great care should be taken when interpreting the
      results of protein localisation and quantitative gene expression patterns using
      fluorescent proteins in experiments involving intracellular physiological change.
      We believe changes in the subcellular environment of the sporulating cell leads
      to conditions that differently alter the spectral properties of GFP and mCherry
      making an accurate interpretation of expression profiles technically challenging.

PMID- 21073757
TI  - Utilization of delivery care among rural women in China: does the health
      insurance make a difference? a cross-sectional study.
AB  - BACKGROUND: Since 2003, the New Cooperative Medical Scheme (NCMS) has been
      implemented throughout rural China, usually covering delivery services in its
      benefit package. The objective of this study was to compare the difference of
      utilization of delivery services, expenditures, and local women's perceived
      affordability between women with and without reimbursement from NCMS. METHODS: A
      cross-sectional survey was carried out in two rural counties in Shaanxi province,
      China, during December 2008-March 2009. Women giving birth from April 2008 to
      March 2009 were interviewed by a structured questionnaire to collect information
      on utilization of delivery services. Multivariable analyses were used to compare
      the differences in outcomes between women with and without reimbursement from
      NCMS. RESULTS: Of the total 1613 women interviewed, 747(46.3%) got reimbursement
      to cover their expenditure on delivery care (NCMS group) and 866(53.7%) paid
      delivery services entirely out of their own pocket (Non-NCMS group). Compared
      with the Non-NCMS group, the NCMS group had significantly more women who
      delivered at hospital. The rate of Caesarean section (CS), proportion of women
      seeking higher level services, and length of hospitalization were similar between
      the two groups. The total hospital costs for delivery services in the NCMS group
      was significantly smaller and after being reimbursed, the out-of-pocket payment
      in the NCMS group was less than a half of that in the Non-NCMS group. Fewer women
      in the NCMS group than in the Non-NCMS group considered their payment for
      delivery services expensive. CONCLUSIONS: There was no evidence of overuse
      delivery services among the women reimbursed by NCMS. Total hospital costs and
      women's costs for delivery services were found lower in the NCMS group,
      subsequently alleviation on women's perceived financial affordability.

PMID- 21073758
TI  - Massive hydrothorax following subclavian vein catheterization.
AB  - Since the introduction of central venous catheterization for monitoring of the
      venous pressure, fluid infusion and hyperalimentation, the literature has been
      full of serious life-threatening complications. Of these complications is the
      false positioning of the central venous catheter and subsequent development of
      pleural effusion. In this report we are describing a case of iatrogenic massive
      pleural effusion following subclavian vein catheterization necessitating
      intercostal tube drainage and mechanical ventilation. The case highlights the
      importance of ensuring adequate positioning of the catheter after insertion
      through aspiration of venous blood, immediate post insertion X-ray and the
      utilization of ultrasound guidance in cases with expected difficult
      catheterization.

PMID- 21073759
TI  - Inequitable access to substance abuse treatment services in Cape Town, South
      Africa.
AB  - BACKGROUND: Despite high levels of substance use disorders in Cape Town,
      substance abuse treatment utilization is low among people from disadvantaged
      communities in Cape Town, South Africa. To improve substance abuse treatment
      utilization, it is important to identify any potential barriers to treatment
      initiation so that interventions to reduce these barriers can be implemented. To
      date, substance abuse research has not examined the factors associated with
      substance abuse treatment utilization within developing countries. Using the
      Behavioural Model of Health Services Utilization as an analytic framework, this
      study aimed to redress this gap by examining whether access to substance abuse
      treatment is equitable and the profile of variables associated with treatment
      utilization for people from poor communities in Cape Town, South Africa. METHODS:
      This study used a case-control design to compare 434 individuals with substance
      use disorders from disadvantaged communities who had accessed treatment with 555
      controls who had not accessed treatment on a range of predisposing, treatment
      need and enabling/restricting variables thought to be associated with treatment
      utilization. A hierarchical logistic regression was conducted to assess the
      unique contribution that the need for treatment, predisposing and
      enabling/restricting variable blocks made on substance abuse treatment
      utilization. RESULTS: Findings revealed that non-need enabling/restricting
      variables accounted for almost equal proportions of the variance in service
      utilization as the need for treatment variables. These enabling/restricting
      variables also attenuated the influence of the treatment need and predisposing
      variables domains on chances of treatment utilization. Several
      enabling/restricting variables emerged as powerful partial predictors of
      utilization including competing financial priorities, geographic access barriers
      and awareness of treatment services. Perceived severity of drug use, a need for
      treatment variable) was also a partial predictor of utilization. CONCLUSIONS:
      Findings point to inequitable access to substance abuse treatment services among
      people from poor South African communities, with non-need factors being
      significant determinants of treatment utilization. In these communities,
      treatment utilization can be enhanced by (i) expanding the existing repertoire of
      services to include low threshold services that target individuals with less
      severe problems; (ii) providing food and transport vouchers as part of
      contingency management efforts, thereby reducing some of the financial and
      geographic access barriers; (iii) introducing community-based mobile outpatient
      treatment services that are geographically accessible; and (iv) employing
      community-based outreach workers that focus on improving awareness of where, when
      and how to access existing treatment services.

PMID- 21073760
TI  - The influence of a biopsychosocial-based treatment approach to primary overt
      hypothyroidism: a protocol for a pilot study.
AB  - BACKGROUND: Hypothyroidism is a prevalent endocrine condition. Individuals with
      this disease are commonly managed through supplementation with synthetic thyroid
      hormone, with the aim of alleviating symptoms and restoring normal thyroid
      stimulating hormone levels. Generally this management strategy is effective and
      well tolerated. However, there is research to suggest that a significant
      proportion of hypothyroid sufferers are being inadequately managed. Furthermore,
      hypothyroid patients are more likely to have a decreased sense of well-being and
      more commonly experience constitutional and neuropsychiatric complaints, even
      with pharmacological intervention.The current management of hypothyroidism
      follows a biomedical model. Little consideration has been given to a
      biopsychosocial approach to this condition. Within the chiropractic profession
      there is growing support for the use of a biopsychosocial-based intervention
      called Neuro-Emotional Technique (NET) for this population. METHODS/DESIGN: A
      placebo-controlled, single-blinded, randomised clinical pilot-trial has been
      designed to assess the influence of Neuro-Emotional Technique on a population
      with primary overt hypothyroidism. A sample of 102 adults (>=18 years) who meet
      the inclusion criteria will be randomised to either a treatment group or a
      placebo group. Each group will receive ten treatments (NET or placebo) over a six
      week period, and will be monitored for six months. The primary outcome will
      involve the measurement of depression using the Depression, Anxiety and Stress
      Scale (DASS). The secondary outcome measures to be used are; serum thyroid
      stimulating hormone, serum free-thyroxine, serum free-triiodothyronine, serum
      thyroid peroxidase auto-antibodies, serum thyroglobulin auto-antibodies as well
      as the measurement of functional health and well-being using the Short-Form-36
      Version 2. The emotional states of anxiety and stress will be measured using the
      DASS. Self-measurement of basal heart rate and basal temperature will also be
      included among the secondary outcome measures. The primary and secondary measures
      will be obtained at commencement, six weeks and six months. Measures of basal
      heart rate and basal temperature will be obtained daily for the six month trial
      period, with recording to commence one week prior to the intervention.
      DISCUSSION: The study will provide information on the influence of NET when added
      to existing management regimens in individuals with primary overt hypothyroidism.
      TRIAL REGISTRATION: ANZCTR Number: 12607000040460.

PMID- 21073761
TI  - alpha-Lipoic acid has anti-inflammatory and anti-oxidative properties: an
      experimental study in rats with carrageenan-induced acute and cotton pellet
      induced chronic inflammations.
AB  - alpha-Lipoic acid (ALA) has been termed the 'ideal' antioxidant, a readily
      absorbed and bioavailable compound capable of scavenging a number of free
      radicals, and it has been used for treating diseases in which oxidative stress
      plays a major role. The present study was designed to gain a better understanding
      for the positive effects of ALA on the models of acute and chronic inflammation
      in rats, and also determine its anti-oxidative potency. In an acute model, three
      doses of ALA (50, 100 and 200 mg/kg) and one dose of indomethacin (25 mg/kg) or
      diclofenac (25 mg/kg) were administered to rats by oral administration. The paw
      volumes of the animals were calculated plethysmometrically, and 0.1 ml of 1 %
      carrageenan (CAR) was injected into the hind paw of each animal 1 h after oral
      drug administration. The change in paw volume was detected as five replicates
      every 60 min by plethysmometry. In particular, we investigated the activities of
      catalase, superoxide dismutase (SOD), glutathione S-transferase (GST),
      glutathione peroxidase (GPx), glutathione reductase (GR), inducible NO synthase
      (iNOS) and myeloperoxidase (MPx), and the amounts of lipid peroxidation (LPO) or
      total GSH in the paw tissues of CAR-injected rats. We showed that ALA exhibited
      anti-inflammatory effects on both acute and chronic inflammations, and a strongly
      anti-oxidative potency on linoleic acid oxidation. Moreover, the administration
      of CAR induced oedema in the paws. ALA significantly inhibited the ability of CAR
      to induce: (1) the degree of acute inflammation, (2) the rise in MPx activity,
      (3) the increases of GST and iNOS activities and the amount of LPO and (4) the
      decreases of GPx, GR and SOD activities and the amount of GSH. In conclusion,
      these results suggest that the anti-inflammatory properties of ALA, which has a
      strong anti-oxidative potency, could be related to its positive effects on the
      antioxidant system in a variety of tissues in rats.

PMID- 21073762
TI  - Is the effect of prior exercise on postprandial lipaemia the same for a moderate
      fat meal as it is for a high-fat meal?
AB  - Moderate-intensity exercise can lower the TAG response to a high-fat meal;
      however, the British diet is moderate in fat, and no study to date has compared
      the effect of such exercise on responses to high-fat and moderate-fat meals. The
      present work investigated the effect of brisk walking performed 13 h before
      intake of both high-fat and moderate-fat meals on postprandial plasma TAG
      concentrations. Eight inactive, overweight men completed four separate 2 d
      trials, i.e. rest (Con) or a 90-min treadmill walk (Ex) on the evening of day 1,
      followed by the ingestion of a moderate-fat (Mod) or high-fat (High) meal on the
      morning of day 2. High-fat meals contained 66 % of total energy as fat, while the
      percentage was 35 % for moderate-fat meals; both the meals were, however,
      isoenergetic. On day 2, venous blood was sampled in the fasted state, 30 and 60
      min after ingesting the test meal and then hourly until 6 h post-meal. Exercise
      reduced plasma TAG concentrations significantly (P < 0.001), with no exercise *
      meal interaction (P = 0.459). Walking reduced the total TAG response to a high
      fat meal by 29 % (relative to High Con); the same bout of exercise performed
      before ingesting a moderate-fat meal lowered total TAG by 26 % (compared with Mod
      Con). The ability of a single moderate-intensity aerobic exercise bout to lower
      postprandial TAG concentrations is just as great, in percentage terms, when the
      test meal ingested is of a moderate rather than a high fat content.

PMID- 21073763
TI  - Occurrence of pathogenic Yersinia enterocolitica and Yersinia pseudotuberculosis
      in small wild rodents.
AB  - Rodents are a potential source of pathogenic Yersinia enterocolitica and Y.
      pseudotuberculosis. In order to study this, 190 rodents were captured and sampled
      on seven pig farms (n=110), five chicken farms (n=55) and six other locations
      (n=25) in Sweden. Pigs from three of the pig farms were also sampled (n=60).
      Pathogenic Y. enterocolitica was detected by TaqMan PCR in about 5% of rodent
      samples and 18% of pig samples. Only rodents caught on pig farms tested positive
      for the pathogen. Y. enterocolitica bioserotype 4/O:3 strains isolated from the
      rodent and pig samples were compared by pulsed-field gel electrophoresis and
      revealed a high degree of similarity, which was confirmed by random amplified
      polymorphic DNA. Y. pseudotuberculosis was only detected in one rodent sample.
      Thus, rodents may be vectors for the transmission of pathogenic Y. enterocolitica
      to pigs, acting as carriers rather than a reservoir, and should therefore remain
      an important issue in hygiene control measures on farms.

PMID- 21073765
TI  - Prevalence of Coxiella burnetii (Q fever) antibodies in bovine serum and bulk
      milk samples.
AB  - Q fever (Coxiella burnetii) is a zoonotic disease of increasing public health
      importance. The objective of this study was to estimate the prevalence of, and
      risk factors associated with, exposure to C. burnetii in cattle in the Republic
      of Ireland. Bulk-tank milk samples from 290 dairy herds and 1659 sera from 332
      dairy and beef herds, randomly sampled, were tested by indirect ELISA to detect
      antibodies to C. burnetii. In total, 37.9% of bulk-milk sample herds and 1.8% of
      sera (from 6.9% of herds) were antibody positive. Of risk factors tested using
      logistic regression analysis, only large herd size (bulk-milk analysis) and dairy
      breed (serum analysis) significantly increased the odds of being positive for
      antibodies to C. burnetii. Herds with positive milk or serum samples were
      randomly distributed throughout the Republic of Ireland and no clustering was
      observed. The use of an ELISA to test bulk-milk samples collected by randomized
      stratified sampling is a cost-effective method by which national herd prevalence
      can be estimated by active surveillance.

PMID- 21073764
TI  - Observational study of the epidemiology and outcomes of vancomycin-resistant
      Enterococcus bacteraemia treated with newer antimicrobial agents.
AB  - Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSI) are a growing
      problem with few clinical trials to guide therapy. We conducted a retrospective
      study of management and predictors of mortality for VRE-BSI at a tertiary-care
      centre from January 2005 to August 2008. Univariate and multivariable analyses
      examined the relationship of patient characteristics and antibiotic therapy with
      30-day all-cause mortality. Rates of VRE-BSI increased from 0.06 to 0.17
      infections/1000 patient-days (P=0.03). For 235 patients, 30-day mortality was
      34.9%. Patients were primarily treated with linezolid (44.2%) or daptomycin
      (36.5%). Factors associated with mortality were haemodialysis [odds ratio (OR)
      3.2, 95% confidence interval (CI) 1.6-6.3, P=0.007], mechanical ventilation (OR
      3.7, 95% CI 1.3-10.4, P=0.01), and malnutrition (OR 2.0, 95% CI 1.0-4.0,
      P=0.046). Use of linezolid, but not daptomycin (P=0.052) showed a trend towards
      an association with survival. In conclusion, VRE-BSI is a growing problem,
      associated with significant 30-day mortality. Multiple factors were associated
      with poor outcomes at our hospital.

PMID- 21073766
TI  - Chikungunya epidemic-related mortality.
AB  - Port Blair, the capital city of the Union Territory of Andaman and Nicobar
      Islands in the republic of India, witnessed an outbreak of chikungunya (CHIK)
      fever in 2006. Although no deaths attributable to CHIK fever were registered,
      thousands of people were affected. In view of evidence from other parts of the
      world indicating that CHIK fever does cause death we studied the mortality trend
      in Port Blair from 2002 to 2008 in order to verify if there was increased
      mortality during the CHIK fever epidemic. The expected number of monthly deaths
      in 2006 was calculated by multiplying the average monthly mortality rate from
      2002 to 2008 (with the exception of 2006) with the monthly population in 2006.
      The results indicated that there was a significant increase in expected deaths
      during some months of 2006, which coincided with the peak in the CHIK fever
      epidemic in Port Blair.

PMID- 21073767
TI  - Prevalence, incidence, and persistence of syphilis infection in female sex
      workers in a Chinese province.
AB  - The study's objectives were to investigate the prevalence, incidence,
      persistence, and associated risk factors of syphilis in female sex workers (FSWs)
      in Kaiyuan City, Yunnan, China. Three serial cross-sectional surveys were
      conducted and biological specimens were collected and tested for HIV, sexually
      transmitted infections, and drug use. The logistic Generalized Estimating
      Equation regression model was used to identify risk factors for prevalent
      syphilis. The prevalence of syphilis was 7.5%, 8.4% and 8.8%, respectively, in
      the three survey periods. Estimated syphilis incidence was 1.07 cases/100 person
      years, and the persistence of syphilis per person at 6 months was 90.4%. In
      multivariate analysis, the factors associated with syphilis were age, lower
      education level, number of clients in a week, inconsistent condom use with
      clients, herpes simplex virus type 2 (HSV-2), and Chlamydia trachomatis.
      Persistent syphilis in this population of FSWs is a serious public health
      concern.

PMID- 21073768
TI  - Endothelial nitric oxide synthase polymorphism (G894T) and nonarteritic anterior
      ischemic optic neuropathy.
AB  - Nonarteritic anterior ischemic optic neuropathy (NAION) is associated with
      vascular risk factors and a genetic predisposition for NAION. In this study, we
      examined the potential association of endothelial nitric oxide synthase (eNOS)
      G894T polymorphism with NAION. For this, 45 patients (29 men and 16 women) and
      193 controls (122 men and 71 women) were enrolled prospectively and genotyped for
      eNOS genes. Genotypes were determined by polymerase chain reaction and
      restriction enzyme analysis. The prevalence of eNOS polymorphisms was estimated
      in NAION patients and controls. Genotype frequencies were estimated with chi
      square test, and odds ratios were calculated. We found that eNOS G894T
      polymorphism is not associated with NAION occurrence as the genotype and allele
      frequencies were not significantly different between the control and patient
      groups (TT vs. GG + GT: P = 0.646 and T vs. G: P = 0.86). The precise mechanism
      of NAION occurrence has not been elucidated yet; since NAION may occur when a
      compromised watershed microcirculation is combined with insufficient
      autoregulation of systematic circulation, other alterations in the eNOS gene or
      polymorphism of genes involved in systematic circulation may be associated with
      NAION occurrence.

PMID- 21073769
TI  - Social engagement and depressive symptoms of elderly residents with dementia: a
      cross-sectional study of 37 long-term care units.
AB  - BACKGROUND: Social engagement and depression are important outcomes for residents
      with dementia in long-term care. However, it is still largely unclear which
      differences in social engagement and depression exist in residents of various
      long-term care settings and how these differences may be explained. This study
      investigated the relationship between social engagement and depressive symptoms
      in long-term care dementia units, and studied whether differences in social
      engagement and depressive symptoms between units can be ascribed to the
      composition of the resident population or to differences in type of care setting.
      METHODS: Thirty-seven long-term care units for residents with dementia in nursing
      and residential homes in the Netherlands participated in the study. Social
      engagement and depressive symptoms were measured for 502 residents with the
      Minimum Data Set of the Resident Assessment Instrument. Results were analyzed
      using multilevel analysis. RESULTS: Residents of psychogeriatric units in nursing
      homes experienced low social engagement. Depressive symptoms were most often
      found in residents of psychogeriatric units in residential homes. Multilevel
      analyses showed that social engagement and depressive symptoms correlated
      moderately on the level of the units. This correlation disappeared when the
      characteristics of residents were taken into account. CONCLUSIONS: Social
      engagement and depressive symptoms are influenced not only by individual
      characteristics but also by the type of care setting in which residents live.
      However, in this study social engagement and depressive symptoms were not
      strongly related to each other, implying that separate interventions are needed
      to improve both outcomes.

PMID- 21073770
TI  - Family socioeconomic status and child executive functions: the roles of language,
      home environment, and single parenthood.
AB  - The association between family socioeconomic status (SES) and child executive
      functions is well-documented. However, few studies have examined the role of
      potential mediators and moderators. We studied the independent and interactive
      associations between family SES and single parenthood to predict child executive
      functions of inhibitory control, cognitive flexibility, and working memory and
      examined child expressive language abilities and family home environment as
      potential mediators of these associations. Sixty families from diverse SES
      backgrounds with a school-age target child (mean [SD] age = 9.9 [0.96] years)
      were evaluated. Child executive functioning was measured using a brief battery.
      The quality of the home environment was evaluated using the Home Observation for
      the Measurement of the Environment inventory. Family SES predicted the three
      child executive functions under study. Single parent and family SES were
      interactively associated with children's inhibitory control and cognitive
      flexibility; such that children from low SES families who were living with one
      parent performed less well on executive function tests than children from
      similarly low SES who were living with two parents. Parental responsivity,
      enrichment activities and family companionship mediated the association between
      family SES and child inhibitory control and working memory. This study
      demonstrates that family SES inequalities are associated with inequalities in
      home environments and with inequalities in child executive functions. The impact
      of these disparities as they unfold in the lives of typically developing children
      merits further investigation and understanding.

PMID- 21073771
TI  - Practice effect and beyond: reaction to novelty as an independent predictor of
      cognitive decline among older adults.
AB  - Practice Effects (PE) have been gaining interest as an early marker of
      pathological cognitive decline among older adults, with cognitively compromised
      individuals exhibiting diminished or absent PE, presumably due to reduced ability
      to learn. However, the opposite pattern has also been observed, with MCI
      participants showing larger PEs than controls. In this prospective cohort study,
      we examined the possibility that individuals with incipient cognitive decline may
      be more "thrown" by task novelty, which may inflate PE due to diminished
      performance during the first exposure to the task. We assessed Novelty Effect
      (NE) and Learning (LRN) on a motor task in 50 community-dwelling independent
      older adults who expressed a concern about their cognition. Results showed that
      larger NE was associated with greater cognitive decline 17 months later, reliably
      classifying participants into decliners and nondecliners. LRN did not
      independently explain any variance in future cognitive change, but moderated the
      relationship between NE and decline and correlated with the level of cognition at
      baseline and follow-up. These findings highlight the differing contributions of
      NE and LRN to PE, and demonstrate that NE may be sensitive to depletion of
      cognitive reserve among individuals who are on the verge of exhibiting a reliable
      cognitive decline.

PMID- 21073772
TI  - Children's accuracy of portion size estimation using digital food images: effects
      of interface design and size of image on computer screen.
AB  - OBJECTIVE: To test the effect of image size and presence of size cues on the
      accuracy of portion size estimation by children. DESIGN: Children were randomly
      assigned to seeing images with or without food size cues (utensils and checked
      tablecloth) and were presented with sixteen food models (foods commonly eaten by
      children) in varying portion sizes, one at a time. They estimated each food
      model's portion size by selecting a digital food image. The same food images were
      presented in two ways: (i) as small, graduated portion size images all on one
      screen or (ii) by scrolling across large, graduated portion size images, one per
      sequential screen. SETTING: Laboratory-based with computer and food models.
      SUBJECTS: Volunteer multi-ethnic sample of 120 children, equally distributed by
      gender and ages (8 to 13 years) in 2008-2009. RESULTS: Average percentage of
      correctly classified foods was 60.3 %. There were no differences in accuracy by
      any design factor or demographic characteristic. Multiple small pictures on the
      screen at once took half the time to estimate portion size compared with
      scrolling through large pictures. Larger pictures had more overestimation of
      size. CONCLUSIONS: Multiple images of successively larger portion sizes of a food
      on one computer screen facilitated quicker portion size responses with no
      decrease in accuracy. This is the method of choice for portion size estimation on
      a computer.

PMID- 21073773
TI  - Effect of inhaled hypertonic saline on hospital admission rate in children with
      viral bronchiolitis: a randomized trial.
AB  - OBJECTIVE: We sought to determine whether inhaled 3% hypertonic saline (HS)
      reduces admission to hospital in ambulatory children with moderately severe viral
      bronchiolitis. Secondary objectives compared changes in respiratory scores before
      and after treatment and assessed the need for unscheduled medical intervention
      within 7 days. METHODS: Children under the age of 2 years presenting with
      moderately severe viral bronchiolitis to the emergency department of 4 general
      hospitals from November 2008 to March 2009 were randomly assigned to receive 3
      consecutive 4-mL doses of nebulized 3% HS (treatment group) or 0.9% normal saline
      (NS; control group) in a double blind fashion, each coadministered with 1 mg
      salbutamol. Outcome measures included the difference in hospital admission rate
      and changes in respiratory distress scores. RESULTS: A total of 81 children (mean
      age 8.9 mo, range 0.7-22 mo) were assessed over 88 visits on an intention-to
      treat basis. No statistically significant differences were found between
      treatment groups. Children in the HS group had a nonsignificant trend toward
      greater improvement compared with NS controls with a same-day admission rate of
      18% (95% confidence interval [CI] 9%-32%) versus 27% (95% CI 16%-42%),
      respectively. Respiratory Assessment Change Scores (RACS) favoured the HS group
      over NS controls (mean RACS 4.7 [95% CI 3.6-5.8] v. 3.7 [95% CI 2.5-4.9],
      respectively), although the CIs overlap and these differences were not
      statistically significant. CONCLUSION: The short-term use of nebulized 3% HS did
      not result in any statistically significant benefits, although a nonsignificant
      trend toward a decrease in admission rate and improvement in respiratory distress
      was found. A larger study would be required to determine whether these trends
      arise from a clinically relevant treatment effect.

PMID- 21073774
TI  - Abdominal pain: a survey of clinically important outcomes for future research.
AB  - OBJECTIVE: We aimed to use the consensus opinion of a group of expert emergency
      physicians to derive a set of emergency diagnoses for acute abdominal pain that
      might be used as clinically significant outcomes for future research. METHODS: We
      conducted a cross-sectional survey of a convenience sample of emergency
      physicians with expertise in abdominal pain. These experts were authors of
      textbook chapters, peer-reviewed original research with a focus on abdominal pain
      or widely published clinical guidelines. Respondents were asked to categorize 50
      possible diagnoses of acute abdominal pain into 1 of 3 categories: 1)
      unacceptable not to diagnose on the first emergency department (ED) visit; 2)
      although optimal to diagnose on first visit, failure to diagnose would not be
      expected to have serious adverse consequences provided the patient had follow-up
      within the next 2-7 days; 3) if not diagnosed during the first visit, unlikely to
      cause long-term risk to the patient provided the patient had follow-up within the
      next 1-2 months. Standard descriptive statistical analysis was used to summarize
      survey data. RESULTS: Thirty emergency physicians completed the survey. Of 50
      total diagnoses, 16 were categorized as "unacceptable not to diagnose in the ED"
      with greater than 85% agreement, and 12 were categorized as "acceptable not to
      diagnose in the ED" with greater than 85% agreement. CONCLUSION: Our study
      identifies a set of abdominal pain conditions considered by expert emergency
      physicians to be clinically important to diagnose during the initial ED visit.
      These diseases may be used as "clinically significant" outcomes for future
      research on abdominal pain.

PMID- 21073775
TI  - Perceptions of emergency medicine residents and fellows regarding competence,
      adverse events and reporting to supervisors: a national survey.
AB  - OBJECTIVE: We sought to characterize the perceptions of emergency medicine (EM)
      residents and fellows of their clinical and procedural competence, as well as
      their attitudes, practices and perceived barriers to reporting these perceptions
      to their supervisors. METHODS: A Web-based survey was distributed to residents
      and fellows, via their residency directors, in all Canadian EM residency programs
      outside of Quebec. RESULTS: Of 220 residents and fellows contacted in 9 of 10 EM
      programs of the Royal College of Physicians and Surgeons of Canada and 12 of 13
      EM programs of The College of Family Physicians of Canada, 82 (37.3%) completed
      all or part of the survey. Response rates varied slightly by question; 25 of 82
      re-spondents (30.5% [95% confidence interval (CI) 19.9%-41.1%]) agreed with the
      statement, "I sometimes feel unsafe or un-qualified with undertaking unsupervised
      responsibilities or procedures, but I do not report this to my senior physician"
      and 32 of 81 (39.5% [95% CI 28.2%-50.8%]) had felt this within the past 6 months.
      Moreover, 34 of 82 (41.5% [95% CI 30.2%-52.7%]) reported their lack of competence
      to a supervisor half the time or less. Trainees reported worry about loss of
      trust, autonomy or respect (38/80, 47.5% [95% CI 35.9%-59.1%]) or reputation
      (32/80, 40.0% [95% CI 28.6%-51.4%]). Nights on-call (30/79, 38% [95% CI 26.6%
      49.3%]), admission decisions (13/79, 16.5% [7.6%-25.3%]) and central line
      insertion (13/79, 16.5% [95% CI 7.6%-25.3%]) were reported to be frequently
      undertaken despite not feeling competent. Suggestions to improve reporting
      included encouragement to report without penalty (41/82, 50.0% [95% CI 38.6%
      61.4%]) and a less judgmental environment (32/82, 39.0% [95% CI 27.9%-50.2%]).
      CONCLUSION: Emergency medicine trainees report that they frequently do not feel
      competent when undertaking responsibilities without supervision. Barriers to
      reporting these feelings or reporting adverse events appear to relate to social
      pressures and authority gradients. Modifications to the training culture are
      encouraged to improve patient safety.

PMID- 21073777
TI  - Low-impact pelvic fractures in the emergency department.
AB  - OBJECTIVE: We examined the records of patients presenting to the emergency
      department (ED) with low-impact pelvic fractures. We describe frequency,
      demographics, management and patient outcomes in terms of ambulatory ability,
      living independence and mortality. METHODS: Patients treated for a pelvic
      fracture over a 2-year period in Kingston, Ont., were identified. We performed a
      retrospective hospital record review to distinguish high- versus low-impact
      injury mechanisms, and to characterize the injury event, ED management and
      outcomes for patients with low-impact fractures. RESULTS: Of 132 pelvic fractures
      identified, 77 were low-impact fractures. Patients were predominantly women (82%)
      with a mean age of 81 years; 96% had some pre-existing medical comorbidity. The
      pubic rami were most commonly involved (86%). The median length of stay in the ED
      was 9.4 hours. Twenty-five patients (32%) were admitted to hospital. Ten patients
      had surgical stabilization, mostly of the acetabulum. Five patients died in
      hospital, 4 from pneumonia and 1 from myocardial infarction. Eight additional
      patients died within 1 year of injury. At discharge, only 18% lived independently
      and 16% walked without aids versus 42% and 38%, respectively, before injury.
      CONCLUSION: Low-impact pelvic fractures affect predominantly elderly women with
      pre-existing comorbidities. A substantial amount of time and resources in the ED
      are used during the workup of these patients and while awaiting their disposition
      from the ED. These injuries are important because they affect independence and
      seem associated with an increased risk of death.

PMID- 21073776
TI  - Presentations to emergency departments for chronic obstructive pulmonary disease
      in Alberta: a population-based study.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a widespread illness
      with an increasing prevalence in older adults; exacerbations resulting in visits
      to the emergency department (ED) are common. We sought to determine the
      epidemiology of COPD presentations to EDs by older adults in Alberta. METHODS:
      Administrative databases were used to examine all ED encounters for COPD from
      April 1999 to March 2005 in Alberta. Data included demographics of patients and
      timing of ED visits. Data analysis included descriptive summaries and age-sex
      directly standardized visit rates (DSVRs). RESULTS: There were 85 330 ED visits
      for acute COPD made by 38 638 patients 55 years of age or older during the study
      period. More men (53.2%) presented, and the mean age at presentation was 72
      years. The age-sex DSVRs remained stable from 2000/01 (24.4/1000) to 2004/05
      (25.6/1000). Presentation rates differed among population subgroups. Overall, 67%
      of visits resulted in discharge from the ED. CONCLUSION: Chronic obstructive
      pulmonary disease is a common presentation in Alberta EDs; however, the rates of
      presentation were stable during the study period, and monthly and hourly trends
      exhibited similar patterns for each year. Disparities based on age, sex, and
      socio-economic and cultural statuses were identified. Targeted interventions
      could be implemented to reduce future ED visits for COPD.

PMID- 21073778
TI  - Variations in the management of pneumonia in pediatric emergency departments:
      compliance with the guidelines.
AB  - OBJECTIVE: We sought to assess compliance with evidence-based guidelines for the
      management of pediatric pneumonia, including the variations in tests ordered and
      antimicrobials prescribed. Our primary hypothesis was that compliance with the
      treatment recommendations from the most current guidelines would be low for
      antimicrobial prescriptions. METHODS: We conducted a chart review at the
      Children's Hospital in London, Ont., to assess variation in the management of
      pediatric pneumonia. All patients aged 3 months to 18 years seen at the pediatric
      emergency department between Apr. 1, 2006, and Mar. 31, 2007, with a diagnosis of
      pneumonia were eligible for inclusion in the study. RESULTS: Compliance with
      management guidelines was 59.7% (95% confidence interval [CI] 53%-66%, n = 211)
      in children 5-18 years old and 83.0% (95% CI 80%-86%, n = 605) in children 3
      months to 5 years old. Significant variation existed in the choice of
      antimicrobial agent for children with pneumonia, with nonrecommended agents
      frequently prescribed. CONCLUSION: Significant variation existed in the
      management of pediatric pneumonia, and adherence to guidelines was low for the
      group of patients aged 5-18 years. Future studies should attempt to provide
      guidance to distinguish between viral and bacterial etiology to allow judicious
      use of antimicrobials.

PMID- 21073779
TI  - Coaching in emergency medicine.

PMID- 21073780
TI  - Portal venous gas in a patient with abdominal pain. Appendicitis.

PMID- 21073781
TI  - A diabetic patient in septic shock. Emphysematous cystitis.

PMID- 21073782
TI  - Fournier gangrene: rapid diagnosis with bedside ultrasonography.

PMID- 21073786
TI  - Nanoparticle probes and mid-infrared chemical imaging for DNA microarray
      detection.
AB  - To date most mid-infrared spectroscopic studies have been limited, due to lack of
      sensitivity, to the structural characterization of a single oligonucleotide probe
      immobilized over the entire surface of a gold-coated slide or other infrared
      substrate. By contrast, widely used and commercially available glass slides and a
      microarray spotter that prints approximately 120-MUm-diameter DNA spots were
      employed in the present work. To our knowledge, mid-infrared chemical imaging
      (IRCI) in the external reflection mode has been applied in the present study for
      the first time to the detection of nanostructure-based DNA microarrays spotted on
      glass slides. Alkyl amine-modified oligonucleotide probes were immobilized on
      glass slides that had been prefunctionalized with succinimidyl ester groups. This
      molecular fluorophore-free method entailed the binding of gold-nanoparticle
      streptavidin conjugates to biotinylated DNA targets. Hybridization was visualized
      by the silver enhancement of gold nanoparticles. The adlayer of silver,
      selectively bound only to hybridized spots in a microarray, formed the external
      reflective infrared substrate that was necessary for the detection of DNA
      hybridization by IRCI in the present proof-of-concept study. IRCI made it
      possible to discriminate between diffuse and specular external reflection modes.
      The promising qualitative results are presented herein, and the implications for
      quantitative determination of DNA microarrays are discussed.

PMID- 21073788
TI  - A matrix-based two-dimensional regularization algorithm for signal-to-noise ratio
      enhancement of multidimensional spectral data.
AB  - We present a new spectral image processing algorithm, the "matrix maximum entropy
      method" (MxMEM), which offers efficient signal-to-noise ratio (SNR) enhancement
      of multidimensional spectral data. MxMEM is based upon two previous
      regularization methods that employ the maximum entropy concept. The first is a
      one-dimensional (1D) algorithm, which smoothes individual vectors, called the two
      point maximum entropy method (TPMEM). The second is a two-dimensional (2D) form
      called 2D TPMEM, that smoothes images but processes them one vector at a time.
      MxMEM is a truly two dimensional image processing algorithm in that its
      "smoothing engine" performs two-dimensional processing in every iteration. We
      demonstrate that this matrix-based construction makes more effective use of two
      dimensionally embedded information and thus confers significant advantages over
      other regularization approaches. In addition, we utilize the concept that
      individual related Raman spectra can be combined in a matrix to form an
      artificial Raman "image". We show that, when processed as an image, superior SNR
      enhancement is achieved compared to processing the same data by TPMEM one
      spectrum at a time.

PMID- 21073787
TI  - Macromolecular concentrations in bovine nasal cartilage by Fourier transform
      infrared imaging and principal component regression.
AB  - Fourier transform infrared imaging (FT-IRI) and principal component regression
      (PCR) were used to quantitatively determine collagen and proteoglycan
      concentrations in bovine nasal cartilage (BNC). An infrared spectral library was
      first established by obtaining eleven infrared spectra from a series of collagen
      and chondroitin 6-sulfate mixed in different ratios. FT-IR images were obtained
      from 6-MUm-thick sections of BNC specimens at 6.25-MUm pixel size. The spectra
      from the FT-IR images were imported into a PCR program to obtain the relative
      concentrations of collagen and proteoglycan in BNC, based on the spectral library
      of pure chemicals. These PCR-determined concentrations agreed with the molecular
      concentrations determined biochemically using an enzyme digestion assay. Use of
      the imaging approach revealed that proteoglycan loss in the specimens occurs
      first at the surface of the tissue block when compared with the middle portion of
      the tissue block. The quantitative correlation of collagen and proteoglycan
      revealed that their infrared absorption peak areas at 1338 and 1072-855 cm(-1)
      can only be used as qualitative indicators of the molecular contents. The use of
      PCR with FT-IRI offers an accurate tool to spatially determine the distributions
      of macromolecular concentration in cartilage.

PMID- 21073789
TI  - Time-resolved diffuse optical spectroscopy: a differential absorption approach.
AB  - A method is presented for the estimate of spectral changes in the absorption
      properties of turbid media from time-resolved diffuse optical spectroscopy. The
      method relies on the hypothesis of constant scattering over the wavelength range
      of interest, but no limitations come from the sample size and shape as the method
      is derived directly from the Beer-Lambert law. The effects of a moderate spectral
      dependence of the scattering properties and of the non-ideal instrument response
      function were investigated theoretically, and the results were confirmed
      experimentally, showing that the method can be profitably applied in cases of
      practical interest.

PMID- 21073790
TI  - In situ monitoring of adipogenesis with human-adipose-derived stem cells using
      surface-enhanced Raman spectroscopy.
AB  - Methods capable of nondestructively collecting high-quality, real-time chemical
      information from living human stem cells are of increasing importance given the
      escalating relevance of stem cells in therapeutic and regenerative medicines.
      Raman spectroscopy is one such technique that can nondestructively collect real
      time chemical information. Living cells uptake gold nanoparticles and transport
      these particles through an endosomal pathway. Once inside the endosome,
      nanoparticles aggregate into clusters that give rise to large spectroscopic
      enhancements that can be used to elucidate local chemical environments through
      the use of surface-enhanced Raman spectroscopy. This report uses 40-nm colloidal
      gold nanoparticles to create volumes of surface-enhanced Raman scattering (SERS)
      within living human-adipose-derived adult stem cells enabling molecular
      information to be monitored. We exploit this method to spectroscopically observe
      chemical changes that occur during the adipogenic differentiation of human
      adipose-derived stem cells over a period of 22 days. It is shown that
      intracellular SERS is able to detect the production of lipids as little as one
      day after the onset of adipogenesis and that a complex interplay between lipids,
      proteins, and chemical messengers can be observed shortly thereafter. After 22
      days of differentiation, the cells show visible and spectroscopic indications of
      completed adipogenesis yet still share spectral features common to the progenitor
      stem cells.

PMID- 21073791
TI  - Low-cost plastic plasmonic substrates for operation in aqueous environments.
AB  - We report a novel design of a multilayer stack to attain surface-plasmon-coupled
      emission (SPCE) enhancements in liquid medium. Variation in thickness of the
      multilayer affects the position and depth of resonance plasmon dips. Numerical
      investigation resulted in an optimal stack configuration that supports long-range
      surface plasmons. SPCE substrates were prepared on plain BK7 glass and Teflon-AF
      coated polycarbonate (PC-T) substrates by modifying their surface functionalities
      using plasma etching. The changes in refractive indices due to the presence of
      the fluoropolymer layer help reduce the SPCE exit angle from alpha = 75 degrees 
      (plain BK7) to alpha = 60 degrees  (PC-T) in water without requiring specialized
      optics.

PMID- 21073792
TI  - Stable, dispersible surface-enhanced Raman scattering substrate capable of
      detecting molecules bound to silica-immobilized ligands.
AB  - A stable surface-enhanced Raman scattering (SERS) substrate is developed through
      immobilization of gold sols onto aminated silica beads. The plasmon resonance is
      established by spacing of gold sols on the bead surface and remains stable over
      extended periods of time due to the large number of amine groups that provide
      stable anchoring of gold to the surface. Unlike planar supports, this substrate
      can be dispersed in a sample, providing high surface area for detection and
      efficient transport of analytes to its surface. This substrate can be used to
      detect the binding of a molecule to ligands on the silica surface, which avoids
      the stability limitations of thiol-bound ligands on gold. Chemical modification
      of the amine groups on the silica surface with benzoic anhydride could be readily
      detected in Raman scattering enhanced by the neighboring gold sols, with nearly
      the same sensitivity as benzylthiol bound directly to the gold surfaces. This
      result suggests future work involving the immobilization of other ligands through
      the residual amine groups to the silica, which could be used to selectively
      attract target analytes to the SERS-active surface.

PMID- 21073794
TI  - Classification of jet fuel properties by near-infrared spectroscopy using fuzzy
      rule-building expert systems and support vector machines.
AB  - Monitoring the changes of jet fuel physical properties is important because fuel
      used in high-performance aircraft must meet rigorous specifications. Near
      infrared (NIR) spectroscopy is a fast method to characterize fuels. Because of
      the complexity of NIR spectral data, chemometric techniques are used to extract
      relevant information from spectral data to accurately classify physical
      properties of complex fuel samples. In this work, discrimination of fuel types
      and classification of flash point, freezing point, boiling point (10%, v/v),
      boiling point (50%, v/v), and boiling point (90%, v/v) of jet fuels (JP-5, JP-8,
      Jet A, and Jet A1) were investigated. Each physical property was divided into
      three classes, low, medium, and high ranges, using two evaluations with different
      class boundary definitions. The class boundaries function as the threshold to
      alarm when the fuel properties change. Optimal partial least squares discriminant
      analysis (oPLS-DA), fuzzy rule-building expert system (FuRES), and support vector
      machines (SVM) were used to build the calibration models between the NIR spectra
      and classes of physical property of jet fuels. OPLS-DA, FuRES, and SVM were
      compared with respect to prediction accuracy. The validation of the calibration
      model was conducted by applying bootstrap Latin partition (BLP), which gives a
      measure of precision. Prediction accuracy of 97 +/- 2% of the flash point, 94 +/-
      2% of freezing point, 99 +/- 1% of the boiling point (10%, v/v), 98 +/- 2% of the
      boiling point (50%, v/v), and 96 +/- 1% of the boiling point (90%, v/v) were
      obtained by FuRES in one boundaries definition. Both FuRES and SVM obtained
      statistically better prediction accuracy over those obtained by oPLS-DA. The
      results indicate that combined with chemometric classifiers NIR spectroscopy
      could be a fast method to monitor the changes of jet fuel physical properties.

PMID- 21073793
TI  - Differentiation of animal fats from different origins: use of polymorphic
      features detected by Raman spectroscopy.
AB  - Food safety requires the development of reliable techniques that ensure the
      origin of animal fats. In the present work, we try to verify the efficacy of
      using the polymorphic features of fats for discriminating animal-fat origins. We
      use Raman spectroscopy to collect the structural information of fat crystals. It
      is shown that a single Raman band at 1417 cm(-1) successfully differentiates pork
      fats from beef fats. This band is known to be characteristic of the beta'
      polymorph of fats. Pork fats show this band because they contain the beta'
      polymorph after rapid cooling to 0  degrees C. In beef-pork-fat mixtures, this
      band is not detected even in the presence of 50% pork fat; an addition of beef
      fat to pork fat is likely to produce a mixed fat with a completely different
      polymorphic behavior. This method seems to have the potential to detect beef
      products contaminated with pork-adipose tissue.

PMID- 21073796
TI  - Deconvolution in acousto-optical tunable filter spectrometry.
AB  - Spectrometers and spectral imaging systems based on the acousto-optical tunable
      filter (AOTF) are becoming commonly used in many different fields in which high
      spectral resolution is crucial, e.g., laser-induced breakdown spectroscopy, Raman
      spectroscopy, and absorption spectroscopy of gases. As AOTFs have many advantages
      over other spectroscopic instruments but lack spectral resolution, a procedure
      for resolution enhancement, composed of point spread function characterization
      and spectrum preprocessing and deconvolution, is proposed. Wiener, Fourier
      wavelet regularized (ForWaRD), Richardson-Lucy, and Wavelet-Lucy deconvolution
      methods were tested and their performances assessed with two deconvolution
      quality measures: resolution enhancement and noise amplification. It was shown
      that the proposed spectral resolution enhancement is feasible and gives good
      results for line spectra and highly dynamic spectra.

PMID- 21073795
TI  - Far-infrared spectroscopy of protein higher-order structures.
AB  - Far-infrared (FIR) spectroscopy in the spectral region of 50-450 cm(-1) was used
      to study a series of protein higher-order structures constructed using beta
      lactoglobulin and polyomavirus capsid protein VP1. There were marked differences
      in the spectra for beta-lactoglobulin monomer and dimer and between untreated
      beta-lactoglobulin and heat-induced gels formed at neutral pH. Untreated beta
      lactoglobulin and heat-induced gels formed at acidic pH exhibited little
      difference in their spectra. Assembly of the quaternary structure of polyomavirus
      virus-like particles also caused large changes in the FIR spectra. These findings
      suggest that FIR spectroscopy may prove useful in studying some protein
      quaternary and higher-order structures. There was evidence of detection of beta
      lactoglobulin dimerization, intermolecular disulfide bonding in heat-induced
      neutral gels, and polyomavirus virus-like particle assembly but no evidence that
      FIR could detect beta-lactoglobulin fibrils with their polymeric structure and
      hydrogen-bonded intermolecular beta-pleated sheeting.

PMID- 21073797
TI  - Selection of multiple optimal absorption transitions for nonuniform temperature
      sensing.
AB  - A crucial aspect in the design of sensors based on absorption spectroscopy
      involves selecting the optimal transitions. Therefore, the goal of this paper is
      to develop a method of selecting multiple optimal transitions for the measurement
      of nonuniform temperature distributions based on absorption spectroscopy.
      Previously developed methods are largely restricted to the relatively simple case
      of selecting two transitions for uniform distributions. Our new method addresses
      the restrictions of previous methods and is applicable to more general cases. The
      method was validated using both numerical tests and experimental results and is
      expected to be useful in the design of sensors based on multispectral absorption
      spectroscopy.

PMID- 21073798
TI  - Optimization of native fluorescence detection of proteins using a pulsed
      nanolaser excitation source.
AB  - We present a mathematical description of the signal-to-noise ratio (S/N) in a
      fluorescence-based protein detector for capillary electrophoresis that uses a
      pulsed ultraviolet (UV) laser at 266 nm as an excitation source. The model
      accounts for photobleaching, detector volume, laser repetition rate, and analyte
      flow rate. We have experimentally characterized such a system, and we present a
      comparison of the experimental data with the predictions of the model. Using the
      model, the system was optimized for test analytes tryptophan, tyrosine, bovine
      serum albumin (BSA), and conalbumin, producing detection limits (3sigma) of 0.67
      nM, 5.7 nM, 0.9 nM, and 1.5 nM, respectively. Based on the photobleaching data, a
      photobleaching cross-section of 1.4 * 10(-18)cm(2) at 266 nm was calculated for
      tryptophan.

PMID- 21073799
TI  - Application of pulsed buffer gas jets for the signal enhancement of laser-induced
      breakdown spectroscopy.
AB  - We report a new simple method for the signal enhancement of laser-induced
      breakdown spectroscopy using a pulsed buffer gas jet. The signal is enhanced up
      to more than 10 fold by using argon gas jets, which are injected through a pulsed
      nozzle onto the sample area to be analyzed. By synchronizing the buffer gas pulse
      with the laser pulse and optimizing the spatial arrangements between the gas jet
      and the sample surface, we have successfully exploited the useful properties of
      the buffer gas in open atmosphere. The signal-enhancement mechanism in our buffer
      gas jet has been discussed. Also, applications to various samples (metal, glass,
      and paper) have been demonstrated.

PMID- 21073800
TI  - Preparation of Eu3+-Y3+ coactivating Na+ based red-emitting luminous materials
      for light-emitting diodes and investigation of its characteristics.
AB  - By solid-state reaction and doping, a series of red-emitting phosphors
      Na(x)Y(0.92-x/3)(MoO(4))(y)(WO(4))(1-y)O(0.5) : zEu(3+) have been synthesized.
      Through optimization of the process conditions and photoluminescent analysis, one
      type of red emission is obtained that matches nicely with ultraviolet light
      emitting diode (UV-LED) chips.

PMID- 21073801
TI  - Semi-quantitative analysis of gentian violet by surface-enhanced Raman
      spectroscopy using silver colloids.
AB  - The viability of the application of surface-enhanced Raman spectroscopy (SERS) to
      the semi-quantitative analysis of the triphenylmethane dye gentian violet was
      examined by using activated borohydride-reduced silver colloids. Raman and SERS
      spectra of aqueous solutions of gentian violet at different pH values were
      acquired for the first time and equally intense SERS signals were obtained at
      both acidic and alkaline pH values. Two maxima intensities observed in the pH
      profile revealed the presence of different ionization states of the dye. The pH
      conditions for SERS were optimized over the pH range 1 to 12 and the biggest
      enhancement for SERS of this charged dye was found to be at pH 2.0; thus, this
      condition was used for semi-quantitative analysis. A good linear correlation was
      observed for the dependence of the signal intensities of the SERS bands at 1620
      cm(-1) (R = 0.999) and 1370 cm(-1) (R = 0.952) on dye concentration over the
      range 10(-6) to 10(-4) mol/L, using laser excitation at 514.5 nm. At
      concentrations of dye above 10(-2) mol/L, the concentration dependence of the
      SERS signals is nonlinear. This is explained as due to the precipitation of
      metallic silver as well as due to saturation caused by complete coverage of the
      SERS substrate. A series of intensities of the band at 1620 cm(-1) measured from
      dye molecules proved that the single-molecule limit of gentian violet is attained
      at the concentration of 10(-9) mol/L.

PMID- 21073802
TI  - Parallel analysis of individual biological cells using multifocal laser tweezers
      Raman spectroscopy.
AB  - We report on the development and characterization of a multifocal laser tweezers
      Raman spectroscopy (M-LTRS) technique for parallel Raman spectral acquisition of
      individual biological cells. Using a 785-nm diode laser and a time-sharing laser
      trapping scheme, multiple laser foci are generated to optically trap single
      polystyrene beads and suspension cells in a linear pattern. Raman signals from
      the trapped objects are simultaneously projected through the slit of a
      spectrometer and spatially resolved on a charge-coupled device (CCD) detector
      with minimal signal crosstalk between neighboring cells. By improving the rate of
      single-cell analysis, M-LTRS is expected to be a valuable method for studying
      single-cell dynamics of cell populations and for the development of high
      throughput Raman based cytometers.

PMID- 21073803
TI  - In vitro evaluation of elastic multiblock co-polymers as a scaffold material for
      reconstruction of blood vessels.
AB  - There is a need to create cell- and histocompatible implant materials, which
      might temporarily replace the mechanical function of a native tissue for
      regenerative therapies. To match the elastic behavior of the native tissue two
      different multiblock co-polymers were investigated: PDC, consisting of poly(p
      dioxanone) (PPDO)/poly(epsilon-caprolactone) (PCL), and PDD, based on
      PPDO/poly((adipinate-alt-1,4-butanediol)-co-(adipinate-alt-ethylene glycol)-co
      adipinate-alt-diethylene glycol) (Diorez). PDC is capable of a shapememory
      effect. Both multiblock co-polymers show an improved elasticity compared to
      materials applied in established vascular prosthesis. PDD is softer than PDC at
      20 degrees C, while PDC maintains its elasticity at 37 degrees C. Thermodynamic
      characteristics indicate a more polar surface of PDD. Low cell adhesion was found
      on surfaces with low molar free energy of hysteresis (DeltaG) derived from
      contact angle measurements in wetting and dewetting mode and high cell adhesion
      on high-DeltaG surfaces. An increasing content of PCL in PDC improved cell
      adhesion and spreading of human umbilical vein endothelial cells. The
      prothrombotic potential of PDD is higher than PDC. Finally, it is concluded that
      PDC is a promising material for vascular tissue engineering because of its
      improved elastic properties, as well as balanced prothrombotic and anti
      thrombotic properties with endothelial cells.

PMID- 21073804
TI  - Application of ion chromatography for the determination of inorganic ions,
      especially thiocyanates, in human semen samples as biomarkers of environmental
      tobacco smoke exposure.
AB  - Tobacco smoking constitutes a significant source of indoor air pollution. Various
      chemical compounds that are emitted during tobacco smoking can have a direct
      cytotoxic effect on spermatozoa by damaging DNA. There is some evidence that
      tobacco smoking in men could affect male fertility. The goals of this study were
      to find relationships between thiocyanates (as biomarkers of environmental
      tobacco smoke exposure) and other inorganic ions in human semen samples and
      present the effectiveness of the proposed sample preparation procedure combined
      with ion chromatography technique for the determination of inorganic ions,
      especially thiocyanates, in human semen samples collected from heavy, moderate,
      and passive smokers, as well as nonsmoking individuals.

PMID- 21073805
TI  - Analysis of six benzodiazepines in vitreous humor by high-performance liquid
      chromatography-photodiode-array detection.
AB  - The purpose of this study was to validate a high-performance liquid
      chromatography-photodiode-array detetion method for the determination of six
      benzodiazepines in vitreous humor. The sample preparation was carried out using
      solid-phase extraction with Oasis HLB cartridges and 10% acetic acid/MeOH as
      elution solvent. The vitreous humor is less affected by postmortem changes and is
      a very useful sample when blood or urine specimens are not available. Linear
      curves for bromazepam, alprazolam, lorazepam, lormetazepam, diazepam, and
      tetrazepam were obtained within the range 0.03-3 MUg/mL, with coefficients of
      correlation lower than 0.999. The limit of detection was 3 ng/mL, and the lower
      limit of quantification was 30 ng/mL for each benzodiazepine. Intra- and
      interassay for precision and accuracy provided results less than 16.81% and
      16.78%, respectively. Recoveries were higher than 68.51% in all cases. Finally,
      the method was applied to determine benzodiazepines in vitreous humor from
      intoxicated patients.

PMID- 21073806
TI  - Distribution of concentrations of cocaine and its metabolites in hair collected
      postmortem from cases with diverse causes/circumstances of death.
AB  - The concentrations and ratios of cocaine, benzoylecgonine (BE), and
      ecgoninemethylester (EME) in 360 head hair segments and 34 pubic hair samples
      collected at coroner's postmortem examinations were reviewed. The cases included
      diverse histories and causes/circumstances of death. The hair was analyzed using
      a validated method published previously; hair was shampoo washed, solvent washed,
      followed by extraction using 0.1 M hydrochloric acid and SPE clean-up, and
      quantitative analysis by gas chromatography-mass spectrometry in selected ion
      monitoring mode. A statistical evaluation demonstrated that, in head hair, the
      respective lower, middle, and upper concentration (ng/mg) ranges were < 10 ng
      total-0.8, > 0.8-18.9, and > 18.9-384.7 cocaine; < 10 ng total-0.6, > 0.6-7.9,
      and > 7.9-142.2 BE; and < 10 ng total-0.3, > 0.3-0.9, and > 0.9-39.5 EME. In
      pubic hair, the concentrations (ng/mg) detected were 0.2-236.2 cocaine, < 10 ng
      total-74.0 BE, and < 10 ng total-3.2 EME. The BE/cocaine ratio range in head hair
      was 0.01-43.00 (mean 1.39, median 0.28), and in pubic hair it was 0.31-2.67 (mean
      0.59, median 0.31). The EME/cocaine ratio in head hair ranged from < 0.01 to 0.46
      (mean 0.04, median 0.02), and in pubic hair, it ranged from < 0.01 to 0.32 (mean
      0.07, median 0.04). Results reported as < 10 ng total were above the limit of
      detection and below the limit of quantitation (LOQ) (LOQ = 0.2 ng/mg for 50 mg of
      hair).

PMID- 21073807
TI  - Determination of ketone bodies in blood by headspace gas chromatography-mass
      spectrometry.
AB  - A gas chromatography-mass spectrometry (GC-MS) method for determination of ketone
      bodies (beta-hydroxybutyrate, acetone, and acetoacetate) in blood is presented.
      The method is based on enzymatic oxidation of D-beta-hydroxybutyrate to
      acetoacetate, followed by decarboxylation to acetone, which was quantified by the
      use of headspace GC-MS using acetone-(13)C(3) as an internal standard. The
      developed method was found to have intra- and total interday relative standard
      deviations < 10% for acetone+acetoacetate levels (~25 to 8300 MUM) and D-beta
      hydroxybutyrate levels (~30 to 16500 MUM). Recovery values varied from 98 to
      107%, demonstrating the suitability of the method for measuring ketone bodies
      over a wide concentration range. The method has been applied to cases in which
      ketoacidosis was suspected as the cause of death in diabetics or chronic
      alcoholics, as well as to cases in which another cause of death was identified.

PMID- 21073808
TI  - Urinary gamma-hydroxybutyrate concentrations in 1126 female subjects.
AB  - gamma-Hydroxybutyrate (GHB) and its metabolic precursor gamma-butyrolactone (GBL)
      are often implicated in cases of drug-facilitated sexual assault (DFSA), although
      definitive confirmation of GHB/GBL ingestion is complicated by GHB's endogenous
      nature and rapid elimination following ingestion. Multiple studies have attempted
      to establish a discriminant limit (generally 10 mg/L) above which urinary GHB
      concentrations can be considered consistent with GHB/GBL consumption. To
      supplement the currently available data, a rapid gas chromatography-mass
      spectrometry method was developed and validated for the analysis of GHB
      (following acidic conversion to GBL) and used to analyze urine samples collected
      from 1126 women (mean = 0.84 mg/L, median = 0.68 mg/L, range = 0.00-5.5 mg/L).
      GHB concentrations were shown to be independent of urinary pH (within the range
      4.6-9.3), age (within the range 18-35 years), body mass index (within the range
      13.8-36.3), and race. Adjusting GHB concentrations with respect to urinary
      specific gravity had little effect on the mean value (0.91 mg/L) and range (0.0
      7.76 mg/L), although a statistically significant trend of increasing GHB
      concentration with specific gravity could be observed. Our results can be taken
      to offer further support for the 10 mg/L discriminant limit for GHB
      administration in antemortem urine samples.

PMID- 21073809
TI  - Development and validation of analytical methods for ultra-trace beryllium in
      biological matrices.
AB  - Beryllium (Be) is still not well understood from a toxicological point of view,
      and studies that involve the determination of different Be compounds species in
      tissues need to be conducted. In this paper we describe the development and
      validation of reliable methods for the detection of ultra-trace levels of Be in
      various biological matrices. Blood and tissues (liver, lung, spleen, and kidney)
      were used in this study. The samples were digested with a mixture of nitric and
      perchloric acids for Be and BeAl and an addition of sulfuric acid was made for
      BeO. The solutions were analyzed by inductively coupled plasma mass spectrometry
      with (6)Li as internal standard. The detection limits are in the order of 0.02
      ng/g for tissue and 0.03 ng/mL for blood, and were compared to existing reference
      methods. To our knowledge, this is the first study that assesses dissolution of
      the different Be compounds in biological matrices, while also undergoing a
      rigorous optimization and complete validation. This method has proven that it is
      reliable, among the most sensitive available in the literature, and that it can
      be used in trace toxicological studies for Be.

PMID- 21073810
TI  - Screening of xenobiotics by ultra-performance liquid chromatography-mass
      spectrometry using in-source fragmentation at increasing cone voltages: library
      constitution and an evaluation of spectral stability.
AB  - In clinical and forensic toxicology, general unknown screening is used to detect
      and identify exogenous compounds. In this study, we aimed to develop a fast (15
      min) comprehensive screening method for 500 toxicologically relevant analytes
      based on ultra-performance liquid chromatography (UPLC) coupled with a quadrupole
      mass spectrometer (MS) system operated in full scan mode. Data were acquired
      using both positive and negative electrospray ionization by scanning across the
      range m/z 80-650. For each ionization mode, data were also collected under
      multiple fragmentation conditions (i.e., at six different cone voltages).
      Consequently, each molecule could be characterized by a combination of retention
      time and up to a maximum of 12 individual spectra. Investigation of the 500
      analytes resulted in the compilation of a library containing 2975 spectra. An
      assessment of the stability of these spectra was evaluated under various
      conditions, that is, the impact of increasing drug concentration and the presence
      of biological matrix. In addition, the transferability of the spectral library
      was assessed by comparison with data acquired using several other instruments of
      same model and from the same manufacturer. These data are presented in addition
      to the utility of the method for the analysis of routine clinical and forensic
      samples. Following extraction, identified compounds were compared to those found
      with two other techniques, one based on immunoassay and the other, on high
      performance liquid chromatography-photodiode-array.

PMID- 21073811
TI  - Enantioselective determination of ondansetron and 8-hydroxyondansetron in human
      plasma from recovered surgery patients by liquid chromatography-tandem mass
      spectrometry.
AB  - A liquid chromatographic-mass spectrometric assay with atmospheric pressure
      chemical ionization for quantification of ondansetron and its main metabolite 8
      hydroxyondansetron in human plasma was presented. The enantiomeric separation was
      achieved on a Chiralcel OD-R column containing cellulose tris-(3,5
      dimethylphenylcarbamate). The validation data were within the required limits.
      The assay was successfully applied to authentic plasma samples. Quantitative
      results from postoperative patients receiving ondansetron demonstrated a great
      interindividual variability in postoperative plasma drug concentrations, the
      metabolites were not detected in their unconjugated form. A wide variation in the
      S-(+)-/R-(-)-ondansetron concentration ratio between 0.14 and 7.18 is indicative
      for a stereoselective disposition or metabolism. In further studies CYP2D6 and
      CYP3A4 genotype dependent metabolism of ondansetron enantiomers as well as of co
      administered drugs and clinical efficacy of the medication should be tested.

PMID- 21073812
TI  - Trazodone, meta-chlorophenylpiperazine (an hallucinogenic drug and trazodone
      metabolite), and the hallucinogen trifluoromethylphenylpiperazine cross-react
      with the EMIT(r)II ecstasy immunoassay in urine.
AB  - A series of patients whose urine screened positive for 3,4
      methylenedioxymethamphetamine (MDMA) using a commercial enzyme immunoassay test
      (Ecstasy EMIT II assay), failed to confirm by substance-specific liquid
      chromatography-tandem mass spectrometry tests for MDMA. Further evaluation of
      these urine specimens indicates that they were positive for trazodone and its
      metabolite meta-chlorophenylpiperazine (m-CPP). Independent tests of standards
      showed significant crossreactivity on the Ecstasy EMIT II assay with trazodone, m
      CPP, and the related recreational drug trifluoromethylphenylpiperazine (TFMPP).
      This is of further forensic significance because m-CPP is emerging as an illicit
      recreational drug in its own right or as an adulterant in illicit cocaine and
      MDMA. The hallucinogen benzylpiperazine was also assessed but found not to cross
      react significantly with this assay. Patients taking trazodone may get false
      positive results on the urine EMIT test for MDMA.

PMID- 21073813
TI  - Comparison of zopiclone concentrations in oral fluid sampled with Intercept((r))
      oral specimen collection device and Statsure Saliva SamplerTM and concentrations
      in blood.
AB  - A clinical study of zopiclone was performed using doses of 5 and 10 mg. Samples
      of oral fluid were collected using the Statsure and Intercept devices, and blood
      samples were collected simultaneously. Concentrations of zopiclone in samples of
      oral fluid and blood were determined with liquid chromatography-mass
      spectrometry, and concentrations in undiluted oral fluid were calculated. The
      concentrations of zopiclone in oral fluid were generally higher when using the
      Intercept compared to the Statsure device; the median oral fluid/whole blood
      concentration ratios were 3.8 (range 1.5-15.9) and 1.9 (range 1.2-4.6),
      respectively (n = 21). The correlation between zopiclone concentrations in oral
      fluid collected with the two devices was fairly poor, r(2) = 0.35. The results
      indicate that the type of sampling device may significantly affect the analytical
      result for zopiclone in sampled oral fluid.

PMID- 21073814
TI  - Two fatal intoxications with the new designer drug methedrone (4
      methoxymethcathinone).
AB  - We report two fatalities involving the new designer drug methedrone, 4
      methoxymethylcathinone. Blood was extracted with ethyl acetate after the addition
      of sodium hydroxide followed by evaporation and derivatization with TFAA before
      gas chromatography-mass spectrometry analysis. Hair was decontaminated and cut
      into segments, and after overnight extraction with acetonitrile/methanol/20 mM
      ammonium formate buffer (pH 3) (10:10:80), samples were analyzed by liquid
      chromatography-tandem mass spectrometry. The first case was treated in hospital,
      and blood was collected for drug screening. The concentration of methedrone in
      antemortem blood was 13.2 MUg/g and in postmortem femoral blood 8.4 MUg/g. The
      second case presented with 9.6 MUg methedrone/g femoral blood, and in a hair
      sample, methedrone was detected in five short segments suggesting exposure to the
      drug during the months prior to death. In living abusers, the blood concentration
      range was 0.2-4.8 MUg/g (n = 11). We conclude that use of methedrone may result
      in accidental death owing to its toxic properties and that the blood
      concentrations found in the two cases are close to those seen in the living. This
      suggests a rather narrow "therapeutic" window and emphasizes the danger in taking
      this kind of drug for recreational purposes.

PMID- 21073815
TI  - Quantification in postmortem blood and identification in urine of tramadol and
      its two main metabolites in two cases of lethal tramadol intoxication.
AB  - Tramadol is an opioid analgesic considered to induce fewer side effects than
      other compounds of this class. It has been extensively prescribed for two
      decades. However, serious complications may occur in case of intoxication. We
      report here two cases of fatal intoxication due to tramadol ingestion. Tramadol,
      O-desmethyltramadol (ODT), and N-desmethyltramadol (NDT) were quantitatively and
      qualitatively determined in postmortem blood and urine, respectively. An HPLC
      method coupled with fluorescence detection was validated using total error
      approach for the analysis of tramadol, ODT, and NDT in blood. In case 1,
      concentrations of tramadol and its metabolites were 7.7 mg/L (tramadol), 1.33
      mg/L (ODT), and 0.6 mg/L (NDT). In case 2, concentrations found were 48.34 mg/L
      (tramadol), 2.43 mg/L (ODT), and 10.09 mg/L (NDT). The tramadol concentration
      found in case 2 is one of the highest ever described in the literature. Opposite
      ratios of ODT/NDT concentrations observed in different cases were suggested to be
      useful for the evaluation of the delay between ingestion and death. However, the
      changes in metabolites levels may also be explained by pharmacokinetic
      interactions and quantitative differences in the activity of the cytochrome-P450
      2D6. Interestingly, norfluoxetine was detected in subtherapeutic levels in case
      2. Most of these aspects in tramadol-related fatalities are reviewed in this
      paper, and an overview of fatal intoxications due to tramadol is presented.

PMID- 21073816
TI  - Up to their necks in hot water: body temperature and the BAC/BrAC ratio.

PMID- 21073817
TI  - High amphetamine/methamphetamine concentrations in urine can cause error codes on
      the Ortho Vitros(r) Fusion 5,1 FS automated chemistry analyzer.

PMID- 21073819
TI  - Early pyrexia after endovascular aneurysm repair: are cultures needed?
AB  - INTRODUCTION: The post-implantation syndrome after endovascular aneurysm repair
      (EVAR) is increasingly recognised. However, when non-vascular trainees are
      responsible for the care of these patients out of hours, many are investigated if
      pyrexial. This study assesses the role of microbiological  investigations in
      pyrexia after endovascular aneurysm repair. PATIENTS AND METHODS: The notes of 75
      EVAR patients were reviewed retrospectively. The incidence of postoperative
      pyrexia and infective complications were calculated and the result of any
      cultures obtained. RESULTS: Overall,  58 (77.3%) patients were pyrexial with 48 h
      of stent insertion. Twenty-four had blood cultures and 12 had urine cultures
      taken within 48 h of surgery. All of these cultures were negative. However, of
      those with a pyrexia after 48 h, one of nine blood cultures and two of 11 urine
      cultures grew  organisms. Five pyrexial patients and one apyrexial patient
      developed a wound infection (a non-significant difference, P = 1.00).
      CONCLUSIONS: Pyrexia within 48 h of EVAR is common. Microbiological investigation
      in the first 48 h in these patients is unrewarding. After 48 h, cultures  are
      more likely to show growth. Although each patient must be assessed clinically for
      signs of sepsis, blood and urine cultures within 48 h of EVAR are generally
      unnecessary.

PMID- 21073820
TI  - A review of needle core biopsy diagnosed radial scars in the Welsh Breast
      Screening Programme.
AB  - INTRODUCTION: Radial scars are benign breast lesions; their appearance on
      mammography may, however, mimic carcinoma. Needle core biopsy is performed for
      pre-operative diagnosis and, currently in Wales, all lesions with benign biopsy
      results are surgically excised. We have reviewed all  cases of needle core biopsy
      diagnosed radial scars from the Welsh breast screening programme, Breast Test
      Wales (BTW), and investigated the outcome of radial scars based on histology from
      surgical excision in order to evaluate the appropriateness of the current
      management of these lesions  in Wales. PATIENTS AND METHODS: All needle core
      biopsy diagnosed radial scars were identified from the BTW screening database
      from the start of screening in 1989 until the end of 2007. RESULTS: A total of
      118 patients were diagnosed with radial scars on needle core biopsy; two patients
      had bilateral radial scars. Median patient age was 54 years (range, 49-68
      years). Ninety-five lesions (79%) were thought to be pure radial scars on needle
      core biopsy; however, only 81 pure radial scars were identified on excision
      biopsy histology. Carcinoma was present in seven patients  and ductal carcinoma
      in situ in nine patients at excision biopsy. In two patients, the cancers
      occurred in lesions reported as pure radial scars on needle core biopsy. Twenty
      two lesions showed atypical ductal or lobular hyperplasia (ADH/ALH) or both on
      excision biopsy; 14 of these  lesions were classed as pure radial scars by needle
      core biopsy. CONCLUSIONS: All core biopsy diagnosed radial scars, presenting as
      screen detected abnormalities, should be excised due to their association with
      premalignant and malignant conditions.

PMID- 21073821
TI  - Straight to colonoscopy: the ideal patient pathway for the 2-week suspected
      cancer referrals?
AB  - INTRODUCTION: The UK has a higher mortality for colon cancer than the European
      average. The UK Government introduced a 2-week referral target for patients with
      colorectal symptoms meeting certain criteria and 62-day target for the delivery
      of treatment from the date of referral for  those patients diagnosed with cancer.
      Hospitals are expected to meet 100% and 95% of these targets, respectively;
      therefore, an efficient and effective patient pathway is required to deliver
      diagnosis and treatment within this period. It is suggested that 'straight-to
      test' will help this  process and we have examined our implementation of
      'straight-to-colonoscopy' as a method of achieving this aim. PATIENTS AND
      METHODS: We carried out a retrospective audit of 317 patients referred under the
      2-week rule over a 1-year period between October 2004 and September 2005 and were
      eligible for 'straight-to-colonoscopy'. Demographic data, appropriateness of
      referral and colonoscopy findings were obtained. The cost effectiveness and
      impact on waiting period were also analysed. RESULTS: A total of 317 patients
      were seen within 2 weeks. Cancer was found in 23 patients  and all were treated
      within 62 days. Forty-four patients were determined by the specialist to have
      been referred inappropriately because they did not meet NICE referral guidelines.
      No cancer was found in any of the inappropriate referrals. The use of straight-to
      test colonoscopy lead to cost  savings of L26,176 (L82.57/patient) in this group
      compared to standard practice. There was no increase in waiting times.
      CONCLUSIONS: Straight-to-colonoscopy for urgent suspected cancer referrals is a
      safe, feasible and cost-effective method for delivery of the 62-day target  and
      did not lead to increase in the endoscopy waiting list.

PMID- 21073822
TI  - Surgical treatment of ingrown toenails in children: what is best practice?
AB  - INTRODUCTION: Surgery for ingrowing toenails carries a significant re-operation
      rate. We reviewed our departmental figures to assess the optimal management of
      these patients. PATIENTS AND METHODS: We performed a 10-year retrospective review
      of all patients undergoing surgery for  ingrown toenails (IGTN) in order to
      determine the operations most commonly used and the re-operation rate of each of
      these procedures. RESULTS: A total of 880 procedures were performed on 414
      patients. The median age at operation was 8.5 years. About half (48%) of children
      underwent two  or more procedures with wedge excision and phenol application
      being the most common initial and repeat procedure. Recurrent surgery was most
      likely following plain avulsion or wedge avulsion without phenol application.
      Excision of the nailbed with phenol application had the lowest recurrence  rate
      at 18.4%. CONCLUSIONS: We recommend wedge resection with phenol application as
      first-line treatment with simple avulsion reserved for severely infected toes.
      Total nail bed excisions should be reserved for patients with significant on
      going morbidity associated with IGTN. Families  must be made aware of the likely
      outcome of IGTN surgery and the choice of operation must be tailored to the
      individual.

PMID- 21073823
TI  - Back to basics--cutting the cord on umbilical infections.
AB  - INTRODUCTION: Surgical site infections (SSIs) are a significant cause of
      postoperative morbidity with laparoscopic surgery associated with lower SSI
      rates. However, a departmental change in our unit to increased laparoscopic
      colorectal surgery resulted in increased wound infection rates  at umbilical
      specimen extraction sites, the cause of which we attempted to elucidate. SUBJECTS
      AND METHODS: Prospectively collected data over an 18-month period (April 2008 to
      September 2009) for laparoscopic colorectal operations in a busy teaching
      hospital were retrospectively analysed,  focusing on operation performed, whether
      pre-operative skin cleansing was employed, nature of specimen extraction
      excision, and rate of umbilical wound infection. Comparison was made with open
      colorectal procedures performed in the preceding year. RESULTS: In total, 275
      laparoscopic colorectal  operations were performed. Over the first 8 months there
      was a significant increase in infection rates when compared with open procedures
      over a similar time period (23.5% vs 8.0%; P = 0.0001). Changing practice to use
      pre-operative skin cleansing and an incision that skirted around,  as opposed to
      traversing, the umbilicus reduced umbilical infection rates significantly from
      23.5% to 11.6% (P = 0.01). Patients undergoing right hemicolectomy benefitted
      more (reduction of 30.0% to 6.9%; P = 0.04) than those undergoing anterior
      resection (26.8% vs 15.6%, P  = 0.13). CONCLUSIONS: Umbilical incisions, when
      extended for specimen extraction, are particularly prone to infection following
      colorectal surgery but rates can be reduced by simple measures such as pre
      operative umbilical cleansing and avoidance of the umbilicus in the incision,
      without  the need for drastic and costly changes in technique or antibiotic
      prophylaxis.

PMID- 21073824
TI  - Evidence-based surgery--evidence from survey and citation analysis in orthopaedic
      surgery.
AB  - INTRODUCTION: The results of a survey on evidence-based surgery (EBS) among
      members of the American Academy of Orthopedic Surgeons (AAOS) and the British
      Orthopaedic Association (BOA) are presented. The study also analyzes the
      citations earned by articles with different levels of evidence  (LOE) to see if
      LOE have any bearing on the importance attached to the articles by authors and
      contributors to the journals. SUBJECTS AND METHODS: The questionnaire was e
      mailed to 1000 randomly chosen consultant orthopaedic surgeons who were members
      of either the AAOS or the BOA. Participants  were provided with the option of
      responding through web-based entry. For citation analysis, citation data were
      gathered from the Journal of Bone and Joint Surgery (American volume) between the
      years 2003 and 2007 (5-year period). RESULTS: The survey showed that awareness
      and access  to EBS have improved greatly over the years. At the present time,
      these factors are not important barriers to the implementation of EBS in clinical
      practice in developed countries. There was a statistically significant difference
      in those with and without additional qualifications with regard  to the approach
      to EBS. However, an equal percentage of surgeons with and without additional
      qualifications felt that it was difficult to adhere to EBS guidelines in daily
      clinical practice. Citation analysis showed that readers of professional journals
      attach importance to LOE category of  the article and tend to cite level-I
      evidence articles more than other articles.

PMID- 21073825
TI  - A review of health care reform in the United States and in Alaska.
AB  - OBJECTIVES: To review the status of health care reform in the U.S. in general and
      in Alaska in particular. STUDY DESIGN: This paper reviews the literature
      concerning health care reform in the U.S. and in Alaska. METHODS: N/A. RESULTS:
      N/A. CONCLUSIONS: The United States spends more per capita on health care than
      any other OECD country, yet its health outcomes such as life expectancy and
      infant mortality lag behind other countries. Health care reform has been a major
      activity of the federal government and of some states for the past several years.
      The 3 goals of optimizing cost, access and quality, at both the national level
      and at the Alaska state level, are discussed. Some of the major policy changes at
      the national level, including payment system reform, enhanced insurance
      regulation and increased attention to prevention, are discussed. The unique
      health care reform challenges in circumpolar Alaska are highlighted and the
      status of current state level reform initiatives is reviewed.

PMID- 21073826
TI  - Giving birth in Greenland: secular change in acceptance of hospital deliveries.
AB  - OBJECTIVES: Until recently, deliveries usually took place at local hospitals. In
      2001- 2003, new guidelines were introduced to streamline the criteria for
      referral to the obstetrical department in Nuuk. This led to an increase in the
      proportion of deliveries in Nuuk but met with some public criticism. The purpose
      of this article is to describe the policies for delivery in a historical context
      and to analyse the response of the general population to the question of what is
      the preferred place of delivery. STUDY DESIGN: Cross-sectional countrywide health
      interview surveys conducted in 1993-1994 and 2005-2008. METHODS: In 1993-1994 and
      2005-2008, 1,219 and 2,154 adult survey participants lived outside Nuuk and
      answered questions about their preferred place for deliveries in cases of normal
      and at-risk pregnancies. Answers were analysed according to age, gender, ethnic
      group, social position and place of residence. RESULTS: The percentage of women
      from other towns who gave birth at the central hospital in Nuuk almost doubled
      from 2001 to 2005, increasing from 10.1% to 19.8%. In 1993-1994, 74.2% of survey
      participants preferred to have normal deliveries at the local hospital compared
      with 85.3% in 2005-2008. In 1993-1994, 21.3% preferred having at-risk deliveries
      at the obstetrical department in Nuuk compared with 45.7% in 2005-2008.
      CONCLUSIONS: The general population has increasingly accepted the professional
      point of view that deliveries should take place in hospital and in a specialized
      department if needed. Whether this is due to the increased focus of the health
      care professionals on referrals since 2001 or to general societal changes is not
      known.

PMID- 21073827
TI  - Equal access for equal need? Constructing and implementing a capitation-based
      formula for the distribution of health care resources in Norway.
AB  - OBJECTIVES: To discuss challenges when developing and implementing a capitation
      based formula for funding health care services in a regionalized health care
      system. STUDY DESIGN: Case study based on the design and implementation of a
      capitation formula in Norway. METHODS: Descriptive study. RESULTS AND
      CONCLUSIONS: In the Norwegian context, policymakers are often given one
      recommended model rather than a menu of options to choose from. This makes it
      more difficult to introduce politically motivated changes, but may also reduce
      the possibility of manipulation by interest groups. A more thorough analysis of
      the merits of different approaches is needed.

PMID- 21073828
TI  - [Women in labor finally allowed to eat and drink].

PMID- 21073829
TI  - [There is not evidence for restricting eating and drinking during labour].
AB  - Views and policies about eating and drinking in labour vary widely across the
      world. There is an increasing trend towards allowing food and fluids during
      labour, although little scientific data exist on its influence on the course of
      labour. Evidence-based recommendations in the form of a guideline on eating and
      drinking in labour is still lacking. Thus, the purpose of the present paper was
      to review the current literature to establish whether there is evidence for
      restricting or allowing food and fluids during normal labour.

PMID- 21073830
TI  - [Antibiotic prophylaxis in relation to dental treatment of patients with hip or
      knee joint prosthesis is seldom necessary].
AB  - A review of the literature with respect to whether antibiotic prophylaxis should
      be recommended in relation to dental treatment of patients with hip or knee joint
      prosthesis. We find no evidence for such a general recommendation. As neutropenic
      patients and patients with rheumatoid arthritis are generally more prone to
      develop periprosthetic infections it can be considered in these cases to give
      prophylactic antibiotics before more extensive dental treatments.

PMID- 21073831
TI  - [The licit opioid consumption in Denmark].
AB  - To identify users and use of opioids in Denmark three databases were combined.
      The latest fifteen years an increase in users has been noted, and the costs of
      opioids have increased from 175 million DKK (1994) to 540 million DKK (2008).
      Oxycodone and transdermal fentanyl constitute 60% of the total annual costs, and
      together with the increasing costs of buprenorphine, the three opioids constitute
      70% of the total costs in the primary health care sector. The largest group of
      users is individuals with acute pain, however, the highest consumption is
      generated by individuals with chronic non-malignant pain.

PMID- 21073832
TI  - [A contact person leads to increased satisfaction among new mothers].
AB  - INTRODUCTION: The aim of this study was to test a new method for continuous
      monitoring of the Danish contact person concept and to evaluate the impact of the
      concept on the mothers' perception of nursing care and on their self-efficacy.
      MATERIAL AND METHODS: This is a descriptive study, carried out at a neonatal unit
      forming part of a department of paediatrics. Using an electronic questionnaire,
      the mothers were asked if they had been given a contact nurse and how they
      assessed the quality of the care and their own self-efficacy. The correlation
      between their experience of being given a contact person and having high scores
      of nursing care and of self-efficacy was analyzed by logistic regression.
      RESULTS: A total of 300 (81%) of the mothers answered the questionnaire. Among
      the mothers who acknowledged having had a contact nurse compared with those who
      did not, odds ratios were > 1 in 10/11 questions concerning assessment of nursing
      care. Concerning the mothers' assessment of their self-efficacy, the odds ratios
      were > 1 in 7/11 questions. None of these were statistically significant.
      CONCLUSION: The study showed a tendency towards a positive impact on nursing care
      when contact persons were allocated to the mothers who were admitted to a
      neonatal ward. The findings were statistically significant in 2/11 questions.

PMID- 21073833
TI  - [Large differences in treatment of depression between departments of psychiatry].
AB  - INTRODUCTION: A large proportion of patients admitted to psychological
      departments and wards suffer from depression. Knowledge is limited about the
      clinical aspects and treatment of depression at admission and discharge, as well
      as about the differences between psychiatric hospitals. The purpose of this study
      was to develop a database for patients admitted to a psychiatric department
      comprising registration of central clinical parameters. MATERIAL AND METHODS: A
      group of senior psychiatrists with research experience selected 12 central
      clinical and treatment parameters. All five hospitals in the Copenhagen area
      participated. Centralised training in the use of Hamilton Depression Rating Scale
      (HDRS) was performed. At discharge the scores on the various parameters were
      reported to a central database. RESULTS: The educational HDRS ratings for the
      departments were rather uniform. The HDRS ratings and Beck Depression Inventory
      (BDI) ratings at admission and discharge were rather uniform between the
      participating departments. A large proportion of patients had depressive symptoms
      at discharge. The most prevalent antidepressants were newer selective serotonin
      reuptake inhibitors and serotonin norepinephrine reuptake inhibitors. Much
      variability was found in the use of medical augmentation strategies and in
      electroconvulsive therapy (ECT). CONCLUSION: The severity of depression at
      admission and discharge were uniform across the participating departments. Many
      patients suffered from depressive symptoms at discharge. Much variability was
      found in the use of medical augmentation strategies and ECT.

PMID- 21073834
TI  - [Automatic mechanical chest compression during helicopter transportation].
AB  - We describe a case story with a drowned, hypothermic trauma patient treated with
      an automatic mechanical chest compression device during helicopter transportation
      to a trauma center. After falling from a 25 meter high bridge into 2  degrees C
      water, she was rescued lifeless 17 minutes later. Advanced life support was
      initiated. During transport by a rescue helicopter, chest compressions were
      effectively provided by Lund University Cardiopulmonary Assist System (LUCAS).
      Upon arrival to a trauma centre approx. 60 minutes later, the patient was treated
      with extracorporal circulation and rewarmed. She was eventually discharged to her
      home with minor loss of cerebral function.

PMID- 21073835
TI  - [Prolonged mechanical cardiopulmonary resuscitation].
AB  - Efficient cardiopulmonary resuscitation (CPR) contributes to improved outcome
      after cardiac arrest. New mechanical devices improve cardiac output. We present a
      case-report with a male patient who was admitted after 55 minutes of out-of
      hospital CPR which was followed by 45 minutes of in-hospital CPR with a
      mechanical device (LUCAS). Cardiac arrest was due to severe electrolyte disorders
      with plasma potassium: 2.0 mmol/L and ionized calcium: 0.87 mmol/L. There were no
      signs of coronary artery disease. The patient was later discharged without
      neurological deficits. Adequate mechanical massage during CPR may improve
      survival. However, randomised clinical trials are warranted.

PMID- 21073836
TI  - Clinical neuropathology, vol. 29 - no. 6/2010.

PMID- 21073837
TI  - A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy
      (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed
      vacuoles.
AB  - Neutral lipid storage disease with myopathy (NLSDM) is a type of lipid storage
      myopathy arising due to a mutation in the PNPLA2 gene encoding an adipose
      triglyceride lipase responsible for the degradation of intracellular
      triglycerides. Herein, we report the cases of two siblings manifesting slowly
      progressive proximal and distal limb weakness in adulthood. One of the patients
      had dilated cardiomyopathy, hearing loss and short stature. Muscle specimens of
      the 2 patients revealed muscular dystrophic features with massive lipid droplets
      and numerous rimmed vacuoles in the fibers. A novel homozygous mutation IVS2+1G >
      A in the PNPLA2 gene was identified in the 2 cases, but not in the healthy
      familial individuals. The presence of massive lipid droplets with muscular
      dystrophic changes and rimmed vacuoles in muscle fibers might be one of the
      characteristic pathological changes of NLSDM.

PMID- 21073838
TI  - Nemaline bodies as unique pathological feature in the course of treated
      dermatomyositis.
AB  - Dermatomyositis was diagnosed on clinical and muscle histological criteria in a
      42-year-old woman. Despite treatment, the patient complained of deterioration of
      her muscle condition. Since her symptoms were discordant with the rest of the
      data, muscle biopsy was performed and disclosed rod-bearing non-atrophic fibers
      as the unique and predominant pathological feature. Their significance is
      examined in this paper.

PMID- 21073839
TI  - Clinical imaging and neuropathological correlations in an unusual case of
      cerebrotendinous xanthomatosis.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage
      disorder due to a deficiency of the mitochondrial enzyme sterol 27-hydroxylase
      (CYP 27) with reduced or no chenodeoxycholic synthesis. This deficiency leads to
      an accumulation of cholestanol in different sites such as the eye lens, central
      nervous system or tendons. We report a 64-year-old female patient with a
      progressive gait disorder associated with cognitive decline since the age of 59.
      The patient had no mental retardation, cataract or chronic diarrhea. Her family
      reported increasing behavioral modifications 10 years previously. Clinical
      examination revealed a spastic paraplegia and bilateral xanthomas on the Achilles
      tendons. Cerebral magnetic resonance imaging (MRI) revealed diffuse hyperintense
      T2 abnormalities in the pyramidal tracts from the internal capsules to the
      cerebral peduncles also Technetium-99m-ECD brain SPECT showed a severe cerebellar
      hypoperfusion. Serum cholestanol analysis was 7 umol/l (N). After 2 years, she
      was bedridden and died of aspiration pneumonia. The neuropathological study
      confirmed the CTX diagnosis and the sequencing analysis revealed that she was
      compound heterozygous for two mutations in the CYP27A1 gene: 1435 C > T (exon 7)
      on one allele and a new mutation, 1017 G > C (exon 5) on the other. The interest
      of the present case is to report neuropathology findings strongly correlated with
      the MRI and SPECT abnormalities.

PMID- 21073840
TI  - In utero development of symmetric thalamic and brainstem necrosis in a preterm
      hydropic stillborn.
AB  - Focal and symmetric necrotic lesions of the brainstem are thought to result from
      fetal hypotension or cardiac arrest in the perinatal period and thus occur in the
      course of postnatal intensive care rather than in utero. Here, we report for the
      first time on brainstem necrosis in a preterm stillborn demonstrating that
      brainstem necrosis occurs already in utero. The preterm stillborn of 28 weeks
      gestation of a mother that suffered from HELLP-syndrome was severely affected by
      a fetal hydrops with bilateral pleural effusions and lung hypoplasia. Bilateral
      tegmental brainstem necrosis and thalamic lesions were detected.

PMID- 21073841
TI  - PNET/ESFT of the cranial vault: a case report.
AB  - A case of peripheral PNET (PNET/ESFT) of the cranial vault is described. A 56
      year-old woman showed a mass with a large cyst in the right temporal region,
      adherent to the meninges, which caused a left hemiparesis with headache and
      confusion. The mass was totally removed. The histological examination showed a
      dense proliferation of small elements, organized in lobules separated by
      reticulin septa. Many circumscribed necroses, vessels with a thick handcuff of
      reticulin, a diffuse mucous degeneration and abundant mitoses were present. The
      cells were positive for Vimentin and CD99. RT-PCR revealed the EWS/FLI1 fusion
      transcript of the t(11,22) (q24;q12) translocation. The patient presented is the
      oldest one of the rare cases of dura-based meningioma-mimicking pPNETs till now
      described. In line with the possible origin from peripheral nerves or roots of
      cauda equina of non-intracranial tumors, those of the vault may derive from
      peripheral sensory nerves of the dura. The differential diagnosis must be made
      with cPNETs which show a worse prognosis and both can benefit from a different
      chemotherapy.

PMID- 21073842
TI  - Cerebral low-grade lymphoma and light chain deposition disease: exceedingly high
      IgG levels in the cerebrospinal fluid as a diagnostic clue.
AB  - Herein, we report the case of a 72-year-old male with an exceedingly rare
      manifestation of a low-grade lymphoma in the brain associated with light chain
      deposition disease (LCDD). The patient presented with epileptic seizures.
      Magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense
      lesions in the right parietal lobe that were suspicious of vasculitis, low-grade
      glioma, or neurosarcoidosis. In the cerebrospinal fluid (CSF), but not in the
      serum, highly elevated IgG was found. A stereotactic biopsy of one cerebral
      lesion was performed. Histopathology revealed a low grade lymphoplasmacytic B
      cell lymphoma with light chain deposition disease (LCDD). Bone marrow biopsy and
      laboratory workup did not show any systemic involvement. LCDD exclusively
      affecting the brain is an exceedingly rare finding. It can be associated with low
      grade B-cell lymphoma. This is the first report of LCDD exclusively affecting the
      brain in an elderly patient. Compared with the two younger patients previously
      reported, the course of the disease was of a slow-evolving nature. In
      constellations of highly elevated IgG in CSF and multiple white matter lesions,
      LCDD should be considered as underlying pathology.

PMID- 21073843
TI  - Anti-apoptotic and growth-promoting markers in adult medulloblastomas.
AB  - AIM: the aim of this study was to investigate the pathologic features,
      proliferation potential and expression of some anti-apoptotic and growth
      promoting markers in adult medulloblastomas. METHOD: we analyzed the
      immunohistochemical expression of survivin, c-KIT, Bcl-2, fascin, p-53 and Ki-67
      in 18 adult medulloblastomas (> 16 years of age). RESULTS: study included 14
      males and 4 females (mean age: 22.9 +/- 8.2). 14 cases were classical, 2
      desmoplastic/nodular and 2 large cell medulloblastomas. Moderate-to-high nuclear
      survivin expression was observed with high percentages (55 - 100%) in all
      medulloblastomas while Bcl-2 was mildly positive in only 1 case. Interestingly,
      mild-to-moderate cytoplasmic c-KIT expression was demonstrated in 16 cases (89%)
      without membranous accentuation. Fascin expression was observed in 13
      medulloblastomas (72%), 9 of which showing moderate to high immunoreactivity.
      Mild p53 expression was present in only 4 cases (22%). Mean Ki-67 index was 20.6%
      (range 8 - 55%). CONCLUSION: frequent nuclear survivin expression implies the
      predominance of anti-apoptotic factors in pathogenesis of adult medulloblastomas.
      It may also be a potential therapeutic target for adult medulloblastomas.
      Although Blc-2 immunoreactivity was previously reported in approximately 30% in
      medulloblastomas, we have observed that it is rarely expressed in the present
      series of adult medulloblastomas. To our knowledge, this is the first study
      evaluating fascin expression in medulloblastomas. Its presence may be related to
      the neuronal differentiation. Mild-to-moderate cytoplasmic c-KIT immunoreactivity
      without membranous staining in adult medulloblastomas may support the previous
      studies reporting low level of c-KIT protein expression with lack of activating
      mutations in medulloblastomas. It seems p53 is rarely involved in the course of
      develepment of adult medulloblastomas.

PMID- 21073844
TI  - A quantitative study of the pathological changes in the cortical white matter in
      variant Creutzfeldt-Jakob disease (vCJD).
AB  - OBJECTIVE: to quantify cortical white matter pathology in variant Creutzfeldt
      Jakob disease (vCJD) and to correlate white and grey matter pathologies. METHODS:
      pathological changes were studied in immunolabeled sections of the frontal,
      parietal, occipital, and temporal cortex of eleven cases of vCJD. RESULTS:
      vacuolation ("spongiform change"), deposition of the disease form of prion
      protein (PrPsc), and a glial cell reaction were observed in the white matter. The
      density of the vacuoles was greatest in the white matter of the occipital cortex
      and glial cell density in the inferior temporal gyrus (ITG). Florid-type PrPsc
      deposits were present in approximately 50% of white matter regions studied. In
      the white matter of the frontal cortex (FC), vacuole density was negatively
      correlated with the densities of both glial cell nuclei and PrPsc deposits. In
      addition, in the frontal and parietal cortices the densities of glial cells and
      PrPsc deposits were positively correlated. In the FC and ITG, there was a
      negative correlation between the densities of the vacuoles in the white matter
      and the number of surviving neurons in laminae V/VI of the adjacent grey matter.
      In the FC, vacuole density in the white matter was negatively correlated with the
      density of the diffuse PrPsc deposits in laminae II/III and V/VI of the adjacent
      grey matter. In addition, the densities of PrPsc deposits in the white matter of
      the FC were positively correlated with the density of the diffuse PrPsc deposits
      in laminae II/III and V/VI and with the number of surviving neurons in laminae
      V/VI. CONCLUSION: the data suggest significant degeneration of cortical white
      matter in vCJD; the vacuolation being related to neuronal loss in the lower
      cortical laminae of adjacent grey matter, PrPsc deposits the result of leakage
      from damaged axons, and gliosis a reaction to these changes.

PMID- 21073845
TI  - Validation of TIMI and GRACE acute coronary risk scores in Alexandria Governorate
      and their role in the comparison of quality of care between hospitals.
AB  - BACKGROUND: Risk stratification in acute coronary syndrome (ACS) aims to identify
      those patients who might benefit prognostically from further investigation and
      treatment. In addition, risk stratification models have been used by health
      authorities and hospitals in quality management activities. AIM: The present
      study aimed at validating the Thrombolysis In Myocardial Infarction (TIMI) and
      The Global Registry of Acute Coronary Events (GRACE) risk scores for prediction
      of mortality in patients with ACS in Alexandria governorate. In addition, the
      study aimed also at using one of the validated risk scores to compare risk
      adjusted mortality among participating hospitals. MATERIAL AND METHODS: The study
      was conducted at hospitals belonging to 3 different health care organizations in
      Alexandria. All admitted patients with the diagnosis of ACS throughout a period
      of 6 months were included in the study (n=606). Discriminatory capacity and
      calibration of the TIMI and GRACE risk scores for detection of in-hospital
      mortality and mortality within six months of index admission were assessed.
      RESULTS: The study showed that both TIMI and GRACE risk scores had high c
      statistics of 0.70 or higher. GRACE scores showed equal or higher c statistics
      than TIMI scores denoting better discriminatory capacity. TIMI risk score showed
      good calibration while GRACE risk score showed lower calibration capacity with
      certain patient categories. The GRACE risk score was used to calculate the
      standardized in-hospital mortality ratio which was higher than 1 for all
      participating hospitals indicating higher than expected mortality for ACS
      patients in these hospitals. CONCLUSIONS AND RECOMMENDATIONS: GRACE risk score
      showed good discriminatory capacity, suggesting that it is suitable for clinical
      use among ACS patients in Alexandria governorate. It was recommended to use GRACE
      risk score for risk adjustment in quality management activities.

PMID- 21073846
TI  - Epidemiology of workplace violence against nursing staff in Ismailia Governorate,
      Egypt.
AB  - BACKGROUND: Violence against health care workers (HCW) or workplace violence in
      general is a major problem affecting health and productivity of HCWs. OBJECTIVES:
      To determine the prevalence and nature of workplace violence against nurses in
      Ismailia governorate, Egypt, and to identify its risk factors and how nurses
      manage it. MATERIAL AND METHODS: Cross-sectional study, using a questionnaire for
      data collection, which includes demographic data, characteristics of workplace
      violence events, and risk factors contributing to workplace violence. All nursing
      staff in four hospitals and twelve Primary Health Care (PHC) Centers, randomly
      selected from Ismailia city were recruited. Out of 1600 distributed
      questionnaires, a total of completed 970 were returned (a 55% response rate).
      RESULTS: 269 (27.7%) of nurses reported abuse of any kind, 187 (69.5%) verbal
      abuse; and 25 (9.3%) physical abuse. Males were more exposed to violence events
      during the past 12 months than females (35.3% versus 24.2%, p<0.05; OR=1.71).
      Being single posed no higher risk of exposure to violence than being married
      (34.8% vs 31.2%, p = 0.083). Changing shifts to night time had a higher odds for
      being assaulted than working a morning shift (p=0.002, OR=1.58). Working in a
      place crowded with colleagues was not protective and had a higher odds of being
      exposed to violence than working with low number of colleagues (p<0.001,
      OR=2.77). The patients were the perpetrators in 62.8% of violence events, while
      their relatives committed 16.7% of events. Only 7.4% of nurses got physical
      injury because of the violence events. A considerable proportion of exposed
      nurses (55.8%) thought that the violence events were preventable. CONCLUSION AND
      RECOMMENDATIONS: Workplace violence against nurses is a significant problem in
      health care settings all over the world and in Ismailia, Egypt. There is a need
      to increase awareness of the problem among health care workers as well as the
      general public. Further large-scale studies should be conducted to more closely
      examine the problem.

PMID- 21073847
TI  - Obesity among Saudi Female University Students: Dietary Habits and Health
      Behaviors.
AB  - BACKGROUND: The remarkable economic growth in Saudi Arabia has affected the
      population life style negatively. The increasing problem of obesity has been
      reported from different regions in the kingdom. The rate of overweight and
      obesity reached 65.4% in the eastern region among females aged 18-74 years old.
      Although there is considerable amount of data on prevalence of obesity, yet, data
      on dietary habits and food consumption pattern are limited. OBJECTIVES: The
      present study is a cross- sectional descriptive study aimed at exploring the BMI
      distribution among university female students. Food consumption pattern and
      health related behaviors were also assessed. MATERIAL AND METHODS: 799 students
      participated in the study; data were collected using self administered
      questionnaire. Body weight and height were measured to calculate the BMI.
      RESULTS: Among the study participants, overweight and obesity reached 47.9%.
      Marriage, presence of obesity among family members, frequency of drinking aerated
      beverages increased the risk of obesity significantly. Misperception of body
      image was reported by 17.4% and 54.2% of obese and overweight students
      respectively. Analysis of dietary habits and life styles indicated the
      predominance of unhealthy behaviors. CONCLUSION AND RECOMMENDATIONS: The study
      results mandate the need for a national strategy to adopt healthy dietary habits
      and life styles.

PMID- 21073848
TI  - Prevalence of latent TB among health care workers in four major tertiary care
      hospitals in Riyadh, Saudi Arabia.
AB  - BACKGROUND: Tuberculosis (TB) infection represents a global health problem and a
      great risk to Health Care Workers (HCWs). Identifying individuals, particularly
      HCWs with latent tuberculosis infection (LTBI) will support TB control through
      chemoprophylaxis and prevent cross-infection. OBJECTIVES: This study aimed to
      identify prevalence of Latent TB among a two-year new hires of HCWs in 4 major
      tertiary care hospitals in Riyadh, Saudi Arabia. MATERIAL AND METHODS: 2650
      recently (2-years) hired HCWs were surveyed for latent TB using Tuberculin Skin
      Test (TST). Data was collected from January 2008 to December 2009. Induration due
      to TST equal to or more than 10 mm. within 48-72 hours was considered positive.
      The results of TST were correlated with other variables such as age group,
      gender, job category, country of origin. RESULTS: as an overall rate, 291(11%)
      out of 2650 were positive for TST, with the highest significant positive rates
      among physicians (14.9%) and nurses (12.9%) compared to students as a reference
      group. No statistically significant difference was detected between both sexes.
      The highest significant positive TST rates were found among HCWs in the age group
      of 50 years and older (32.6%) compared to 10-19 years age group as a reference
      group, and among HCWs coming from sub-Saharan countries (61.1%) compared to Saudi
      HCWs with the lowest positive rates (5%) as a reference group. CONCLUSION AND
      RECOMMENDATIONS: LTB is prevalent among newly hired HCWs in Riyadh tertiary
      hospitals. Standard programs for detection and treatment of LTB should be
      encouraged.

PMID- 21073849
TI  - Knowledge, Attitudes and Practices Related to Avian Influenza among a Rural
      Community in Egypt.
AB  - BACKGROUND: Avian influenza (AI) is currently a threat to global health.
      Prevention and control largely depend on population awareness and behavior. AIM
      OF STUDY: Is to assess the rural community knowledge, attitudes, and practice
      (KAP) related to AI prevention and control. MATERIAL AND METHODS: A household
      survey, using an interviewing questionnaire and observational checklist, was
      conducted in Bahetim district, Qalubeya Governorate. RESULTS: Of the total 399,
      41.1% were dealing with poultry, of them 26% were raising poultry at their home.
      Vaccination of birds were reported by 66.6% of the respondents, hand washing
      regularly with water and soap by 54.6%, and by going far away from infected birds
      by 51.3%. Nearly 50% mentioned that AI disease cannot be transmitted from person
      to person and that AI is transmitted to human through contact with sick birds.
      Regarding their score level, 75.7% of the respondents had fair knowledge level,
      87.5% had positive attitude towards prevention and control of AI and 58.1% had
      fair practice level. Younger persons, those who had completed secondary or higher
      level of education, those living in nuclear family had better knowledge and
      positive attitudes towards AI prevention and control (p < 0.05), while age, sex,
      and education level did not affect their healthy behavior and sanitary practices.
      CONCLUSIONS AND RECOMMENDATIONS: The level of community knowledge and practices
      about AI disease was moderate, but their attitudes were positive. Therefore,
      designing and implementing health educational programs about AI to improve the
      community practices should have the priority to encourage people to take a more
      active role.

PMID- 21073850
TI  - Smoking habits among Iranian general practitioners.
AB  - BACKGROUND: Smoking is one of the most important public health problems and a
      major cause of morbidity and mortality. General practitioners (GPs) as a key
      person play a great role in public health policy and public smoking behaviors.
      OBJECTIVES: This study aimed to identify general practitioners' smoking
      practices. The main research question was what proportions of physicians are
      smoking and what their pattern of smoking is. MATERIAL AND METHODS: This cross
      sectional study was carried out using a WHO-based questionnaire. A sample size of
      5140 general practitioners selected by stratified random sampling method from a
      total of 25,600 practitioners all over the country at the time of the study
      participated in the study. RESULTS: Seventy four percent of the subjects were
      males. Out of them, 22.3% had a history of smoking at some point of their life;
      about 4.6 % have ceased it; 8.3% had occasional history of smoking and the
      remaining 7.6% mentioned a daily smoking pattern, while 77.7% of them have never
      smoked. At the time of study, 15% were smoking. About 60% of smoking physicians
      had started smoking from the age of 21-30 years. The mean, the minimum and the
      maximum number of daily cigarettes were respectively 6.62 +/- 6.15, 1, and 40
      cigarettes. After cigarettes, the most common tobacco products used by physicians
      were respectively pipes (4.7%), Shisha (4.3%), and cigars (3.9%). There were
      significant relationship between smoking pattern of GPs and some factors such as
      their age of onset of smoking, gender, knowledge about smoking side effects, and
      attitude towards smoking (p<0.001). CONCLUSION AND RECOMMENDATIONS: A
      considerable proportion of Iranian practitioners were currently smoking. There is
      a need for specific strategies to encourage smoking physicians to quit. These
      data should help policy makers and other key persons seeking effective programs
      to reduce tobacco use among GPs in Iran.

PMID- 21073851
TI  - Cross neutralization of Hypnale hypnale (hump-nosed pit viper) venom by
      polyvalent and monovalent Malayan pit viper antivenoms in vitro and in a rodent
      model.
AB  - Hypnale hypnale (hump-nosed pit viper) is a medically important venomous snake in
      Sri Lanka and Southwestern India. Bite of this snake may result in hemostatic
      dysfunction, acute kidney injury and death. Clinical studies indicated that the
      locally available polyvalent antivenoms produced in India are not effective
      against hump-nosed pit viper envenoming. Hence, there is an urgent need to search
      for effective antivenom. In this paper, we examined the ability of Calloselasma
      rhodostoma (Malayan pit viper) monovalent antivenom and the Hemato polyvalent
      antivenom (both produced by Thai Red Cross Society, TRCS) to neutralize the
      lethality and toxic effects of H. hypnale venom, as C. rhodostoma is considered a
      sister taxon of H. hypnale. In vitro neutralization studies showed that the
      Hemato polyvalent antivenom effectively neutralized the lethality of H. hypnale
      venom (1.52mgvenom/mL antivenom) as well as the hemorrhagic, procoagulant and
      necrotic activities of the venom. The monovalent C. rhodostoma antivenom could
      also neutralize the lethality and toxic activities of the venom, but the potency
      was lower. The Hemato polyvalent antivenom also effectively protected mice from
      the lethal and local effects of H. hypnale venom in an in vivo rodent model of
      envenoming. Furthermore, the polyvalent antivenom could also effectively
      neutralize the venom of Daboia russelii (2.50mgvenom/mL antivenom), another
      common cause of snake bites in Sri Lanka and South India. These findings
      suggested that the Hemato polyvalent antivenom may be beneficial in the antivenom
      treatment of H. hypnale envenoming.

PMID- 21073852
TI  - Simultaneous determination of equilibrium constants and enthalpy changes by
      titration calorimetry: Methods, instruments, and uncertainties.
AB  - Calorimetric methods have been used to determine equilibrium constants since
      1937, but no comprehensive review of the various calorimeters and methods has
      been done previously. This article reports methods for quantitative comparison of
      the capabilities of calorimeters for simultaneous determination of equilibrium
      constants and enthalpy changes, for determining optimal experimental conditions,
      and for assessing the effects of systematic and random errors on the accuracy and
      precision of equilibrium constants and enthalpy changes determined by this
      method.

PMID- 21073853
TI  - Application of a high-throughput fluorescent acetyltransferase assay to identify
      inhibitors of homocitrate synthase.
AB  - Homocitrate synthase (HCS) catalyzes the first step of l-lysine biosynthesis in
      fungi by condensing acetyl-coenzyme A and 2-oxoglutarate to form 3R-homocitrate
      and coenzyme A. Due to its conservation in pathogenic fungi, HCS has been
      proposed as a candidate for antifungal drug design. Here we report the
      development and validation of a robust fluorescent assay for HCS that is amenable
      to high-throughput screening for inhibitors in vitro. Using this assay,
      Schizosaccharomyces pombe HCS was screened against a diverse library of
      approximately 41,000 small molecules. Following confirmation, counter screens,
      and dose-response analysis, we prioritized more than 100 compounds for further in
      vitro and in vivo analysis. This assay can be readily adapted to screen for small
      molecule modulators of other acyl-CoA-dependent acyltransferases or enzymes that
      generate a product with a free sulfhydryl group, including histone
      acetyltransferases, aminoglycoside N-acetyltransferases, thioesterases, and
      enzymes involved in lipid metabolism.

PMID- 21073854
TI  - Highly selective L-threonine 3-dehydrogenase from Cupriavidus necator and its use
      in determination of L-threonine.
AB  - l-Threonine level in blood plasma is a biomarker of some diseases and nitrogen
      imbalance in the body. The determination of l-threonine is interesting and is
      required for diagnosis and management of inherited metabolic disorder. This is
      the first report of the specific enzymatic determination of l-threonine by a
      newly discovered l-threonine 3-dehydrogenase (ThrDH, EC 1.1.1.103) from
      Cupriavidus necator NBRC 102504. ThrDH, a key enzyme in l-threonine catabolism in
      microorganisms and animals, catalyzes the NAD(+)-dependent oxidation of l
      threonine to 2-amino-3-oxobutyrate. ThrDH from C. necator was purified to
      homogeneity and fully characterized. l-Threonine and dl-2-amino-3-hydroxyvalerate
      are the only substrates for ThrDH among other l-amino acids, alcohols, and amino
      alcohols. The primary amino acid structure of ThrDH belongs to the extended short
      chain alcohol dehydrogenase superfamily and is related to GDP-mannose-3',5'
      epimerase (GME) from Arabidopsis thaliana. Both enzymes have a glycine-rich
      NAD(+)-binding domain at the N terminal and conserved catalytic triad of YxxxK
      residues, but substrate-binding residues of GME were not found in the ThrDH
      sequence. ThrDH significantly differs from known bacterial and archaea ThrDHs
      that belong to zinc-binding medium chain alcohol dehydrogenase because of low
      sequence similarity and the lack of a zinc-binding domain in the sequence. A
      specific, quantitative, and sensitive enzymatic endpoint method for l-threonine
      determination was developed by using a ThrDH microplate assay. The assay was
      successfully applied for determination of l-threonine in human serum and plasma.
      Our specific determination is simple, convenient, inexpensive, accurate, and
      suitable for mass screening determination of l-threonine in a number of samples.

PMID- 21073855
TI  - On the role of anionic lipids in charged protein interactions with membranes.
AB  - We investigate the role of anionic lipids in the binding to, and subsequent
      movement of charged protein groups in lipid membranes, to help understand the
      role of membrane composition in all membrane-active protein sequences. We
      demonstrate a small effect of phosphatidylglycerol (PG) lipids on the ability of
      an arginine (Arg) side chain to bind to, and cross a lipid membrane, despite
      possessing a neutralizing charge. We observe similar membrane deformations in
      lipid bilayers composed of phosphatidylcholine (PC) and PC/PG mixtures, with
      comparable numbers of water and lipid head groups pulled into the bilayer
      hydrocarbon core, and prohibitively large ~20 kcal/mol barriers for Arg transfer
      across each bilayer, dropping by just 2-3 kcal/mol due to the binding of PG
      lipids. We explore the causes of this small effect of introducing PG lipids and
      offer an explanation in terms of the limited membrane interaction for the choline
      groups of PC lipids bound to the translocating ion. Our calculations reveal a
      surprising lack of preference for Arg binding to PG lipids themselves, but a
      small increase in interfacial binding affinity for lipid bilayers containing PG
      lipids. These results help to explain the nature of competitive lipid binding to
      charged protein sequences, with implications for a wide range of membrane binding
      domains and cell perturbing peptides.

PMID- 21073856
TI  - Mode of action of parasporin-4, a cytocidal protein from Bacillus thuringiensis.
AB  - Parasporin-4 (PS4) is a cytotoxic protein produced by Bacillus thuringiensis
      strain A1470. It exhibits specific cytotoxicity against human cancer cell lines,
      CACO-2, Sawano, and MOLT-4 cells, in particular. When cells were administrated
      with PS4, cell swelling and nuclear shrinkage were induced, and, the ballooned
      cells burst within 24 h. PSI-BLAST search showed that the protein shared homology
      not only with B. thuringiensis Cry toxins but also with aerolysin-type beta-pore
      forming toxins. Circular dichroism measurements suggested that PS4 was a beta
      sheet-rich protein. PS4 aggregated into oligomers on the plasma membrane of PS4
      susceptible CACO-2 cells, but not on that of PS4-resistant HeLa cells. Leakage of
      lactate dehydrogenase and influx of extracellular FITC-dextrans were observed
      only in susceptible cells. The activation of effectors caspase 3 and/or 7 was not
      observed in PS4-treated CACO-2 cells. It was shown that cytotoxicity of the PS4
      against CACO-2 cells was exhibited when treated by cyclodextrin which induces
      cholesterol depletion. These results suggest that PS4 is a unique beta-pore
      forming toxin with a cholesterol-independent activity.

PMID- 21073857
TI  - Decrease in transient receptor potential melastatin 6 mRNA stability caused by
      rapamycin in renal tubular epithelial cells.
AB  - Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is used in
      treatments for transplantation and cancer. Rapamycin causes hypomagnesemia,
      although precisely how has not been examined. Here, we investigated the effect of
      rapamycin on the expression of transient receptor potential melastatin 6 (TRPM6),
      a Mg2+ channel. Rapamycin and LY-294002, an inhibitor of phosphatidilinositol-3
      kinase (PI3K) located upstream of mTOR, inhibited epidermal growth factor (EGF)
      induced expression of the TRPM6 protein without affecting TRPM7 expression in rat
      renal NRK-52E epithelial cells. Both rapamycin and LY-294002 decreased EGF
      induced Mg2+ influx. U0126, a MEK inhibitor, inhibited EGF-induced increases in c
      Fos, p-ERK, and TRPM6 levels. In contrast, neither rapamycin nor LY-294002
      inhibited EGF-induced increases in p-ERK and c-Fos levels. EGF increased p-Akt
      level, an effect inhibited by LY-294002 and 1L-6-hydroxymethyl-chiro-inositol2
      [(R)-2-O-methyl-3-O-octadecylcarbonate] (Akt inhibitor). Akt inhibitor decreased
      TRPM6 level similar to rapamycin and LY-294002. These results suggest that a
      PI3K/Akt/mTOR pathway is involved in the regulation of TRPM6 expression.
      Rapamycin inhibited the EGF-induced increase in TRPM6 mRNA but did not inhibit
      human TRPM6 promoter activity. In the presence of actinomycin D, a
      transcriptional inhibitor, rapamycin accelerated the decrease in TRPM6 mRNA.
      Rapamycin decreased the expression and activity of a luciferase linked with the
      3'-untranslated region of human TRPM6 mRNA. These results suggest that TRPM6
      expression is up-regulated by a PI3K/Akt/mTOR pathway and rapamycin reduces TRPM6
      mRNA stability, resulting in a decrease in the reabsorption of Mg2+.

PMID- 21073858
TI  - Transmembrane helix 7 in the Na+/dicarboxylate cotransporter 1 is an outer helix
      that contains residues critical for function.
AB  - Citric acid cycle intermediates, including succinate and citrate, are absorbed
      across the apical membrane by the NaDC1 Na+/dicarboxylate cotransporter located
      in the kidney and small intestine. The secondary structure model of NaDC1
      contains 11 transmembrane helices (TM). TM7 was shown previously to contain
      determinants of citrate affinity, and Arg-349 at the extracellular end of the
      helix is required for transport. The present study involved cysteine scanning
      mutagenesis of 26 amino acids in TM7 and the associated loops. All of the mutants
      were well expressed on the plasma membrane, but many had low or no transport
      activity: 6 were inactive and 7 had activity less than 25% of the parental. Three
      of the mutants had notable changes in functional properties. F336C had increased
      transport activity due to an increased Vmax for succinate. The conserved residue
      F339C had very low transport activity and a change in substrate selectivity.
      G356C in the putative extracellular loop was the only cysteine mutant that was
      affected by the membrane-impermeant cysteine reagent, MTSET. However, direct
      labeling of G356C with MTSEA-biotin gave a weak signal, indicating that this
      residue is not readily accessible to more bulky reagents. The results suggest
      that the amino acids of TM7 are functionally important because their replacement
      by cysteine had large effects on transport activity. However, most of TM7 does
      not appear to be accessible to the extracellular fluid and is likely to be an
      outer helix in contact with the lipid bilayer.

PMID- 21073859
TI  - Towards a structural understanding of the smallest known oncoprotein:
      investigation of the bovine papillomavirus E5 protein using solution-state NMR.
AB  - The homodimeric E5 protein from bovine papillomavirus activates the platelet
      derived growth factor beta receptor through transmembrane (TM) helix-helix
      interactions leading to uncontrolled cell growth. Detailed structural information
      for the E5 dimer is essential if we are to uncover its unique mechanism of
      action. In vivo mutagenesis has been used to identify residues in the TM domain
      critical for dimerization, and we previously reported that a truncated synthetic
      E5 peptide forms dimers via TM domain interactions. Here we extend this work with
      the first application of high-resolution solution-state NMR to the study of the
      E5 TM domain in SDS micelles. Using selectively 15N-labelled peptides, we first
      probe sample homogeneity revealing two predominate species, which we interpret to
      be monomer and dimer. The equilibrium between the two states is shown to be
      dependent on detergent concentration, revealed by intensity shifts between two
      sets of peaks in 15N-(1)H HSQC experiments, highlighting the importance of sample
      preparation when working with these types of proteins. This information is used
      to estimate a free energy of association (DeltaGx degrees =-3.05 kcal mol(-1))
      for the dimerization of E5 in SDS micelles. In addition, chemical shift changes
      have been observed that indicate a more pronounced change in chemical environment
      for those residues expected to be at the dimer interface in vivo versus those
      that are not. Thus we are able to demonstrate our in vitro dimer is comparable to
      that defined in vivo, validating the biological significance of our synthetic
      peptide and providing a solid foundation upon which to base further structural
      studies. Using detergent concentration to modulate oligomeric state and map
      interfacial residues by NMR could prove useful in the study of other homo
      oligomeric transmembrane proteins.

PMID- 21073860
TI  - Spin-echo EPR of Na,K-ATPase unfolding by urea.
AB  - Denaturant-perturbation and pulsed EPR spectroscopy are combined to probe the
      folding of the membrane-bound Na,K-ATPase active transport system. The Na,K
      ATPase enzymes from shark salt gland and pig kidney are covalently spin labelled
      on cysteine residues that either do not perturb or are essential to hydrolytic
      activity (Class I and Class II -SH groups, respectively). Urea increases the
      accessibility of water to the spin-labelled groups and increases their mutual
      separations, as recorded by D2O interactions from ESEEM spectroscopy and
      instantaneous spin diffusion from echo-detected EPR spectra, respectively. The
      greater effects of urea are experienced by Class I groups, which indicates
      preferential unfolding of the extramembrane domains. Conformational heterogeneity
      induced by urea causes dispersion in spin-echo phase-memory times to persist to
      higher temperatures. Analysis of lineshapes from partially relaxed echo-detected
      EPR spectra indicates that perturbation by urea enhances the amplitude and rate
      of fluctuations between conformational substates, in the higher temperature
      regime, and also depresses the glasslike transition in the protein. These non
      native substates that are promoted by urea lie off the enzymatic pathway and
      contribute to the loss of function.

PMID- 21073861
TI  - The kinetics of YOYO-1 intercalation into single molecules of double-stranded
      DNA.
AB  - The cyanine dye, YOYO-1, has frequently been used in single DNA molecule imaging
      work to stain double-stranded DNA as it fluoresces strongly when bound. The
      binding of YOYO-1 lengthens the DNA due to bis-intercalation. We have
      investigated the kinetics of binding, via this increase in DNA length, for
      single, hydrodynamically-stretched molecules of lambda DNA observed via Total
      Internal Reflection Fluorescence (TIRF) microscopy. The rate and degree of
      lengthening in 40mM NaHCO(3) (pH 8.0) buffer depend upon the free dye
      concentration with the reaction taking several minutes to reach completion even
      in relatively high, 40nM, concentrations of YOYO-1. In the absence of
      overstretching of the DNA molecule, we determine the second order rate constant
      to be 3.8+/-0.7*10(5)s(-1)M(-1), the dissociation constant to be 12.1+/-3.4nM and
      the maximum DNA molecule extension to be 36+/-4%. The intercalation time constant
      (inverse of the pseudo-first order rate constant), tau, decreased from 309 to 62s
      as YOYO-1 levels increased from 10 to 40nM. The kinetics of binding help with
      interpretation of the behavior of DNA-YOYO-1 complexes when overstretched and
      establish defined conditions for the preparation of DNA-YOYO-1 complexes.

PMID- 21073862
TI  - Human proteins that specifically bind to 8-oxoguanine-containing RNA and their
      responses to oxidative stress.
AB  - Exposure of cells to oxygen radicals damage various biologically important
      molecules. Among the oxidized bases produced in nucleic acids, 8-oxo-7,8
      dihydroguanine (8-oxoguanine) is particularly important since it causes base
      mispairing. To ensure accurate gene expression, organisms must have a mechanism
      to discriminate 8-oxoguanine-containing RNA from normal transcripts. We searched
      for proteins that specifically bind to 8-oxoguanine-containing RNA from human
      HeLa cell extracts, and the candidate proteins were identified using mass
      spectrometry. Among the identified candidates, splicing isoform 1 of
      heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) and splicing isoform C1 of
      heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) exhibited strong abilities
      to bind to oxidized RNA. The amount of HNRNPD protein rapidly decreased when
      cells were exposed to hydrogen peroxide, an agent that enhances oxidative stress.
      Moreover, the suppression of HNRNPD expression by siRNA caused cells to exhibit
      an increased sensitivity to hydrogen peroxide. The application of siRNA against
      HNRNPC also caused an increase in sensitivity to hydrogen peroxide. Since no
      additive effect was observed with a combined addition of siRNAs for HNRNPD and
      HNRNPC, we concluded that the two proteins may function in the same mechanism for
      the accurate gene expression.

PMID- 21073863
TI  - Inhibition of neurotrophin receptor p75 intramembran proteolysis by gamma
      secretase inhibitor reduces medulloblastoma spinal metastasis.
AB  - Medulloblastoma (MB) is the most devastating and common pediatric brain tumor.
      Tumor cells invading into surrounding tissue and disseminating through
      cerebrospinal fluid make treatment extremely difficult. Identifying the
      mechanisms of MB cells is therefore imperative for the development of novel
      treatments. A research group demonstrated recently that the multifunctional
      signaling protein neurotrophin receptor p75(NTR) is a central regulator for
      glioma invasion. gamma-secretase mediated processing of the p75(NTR) is a major
      contributor to the highly invasive nature of malignant gliomas. In this study we
      examine the p75(NTR) expression and processing in medulloblastoma cells. Results
      show that p75(NTR) is a critical regulator of medulloblastoma spinal metastasis.
      gamma-secretase inhibitor, which blocks p75(NTR) proteolytic processing,
      significantly abrogates p75(NTR) induced medulloblastoma migration and invasion
      in vitro and in vivo. This data suggests that p75(NTR) is also an important
      therapeutic target for MB. gamma-secretase inhibitor may be a potentially
      effective clinical application for the treatment of medulloblastoma spinal
      metastasis.

PMID- 21073864
TI  - Induced thyme product prevents VEGF-induced migration in human umbilical vein
      endothelial cells.
AB  - Compounds with anti-angiogenic properties are useful in combating cancer by
      preventing new blood vessel formation to support the tumor. In this report we
      introduce a rapid method for screening potential anti-angiogenic compounds in a
      model system that stimulates the production of secondary defense chemicals in
      plants. This methodology identified an inducible vascular factor (IVF3), which
      was found to be inhibitory in all of the model systems tested. Thyme plants were
      exposed to highly vascular mint plants and the methanol extracts were analyzed by
      reverse phase HPLC. The thyme compounds induced by the invading mint tissue, and
      not present in the thyme plants grown alone, were tested in a vertical plate
      assay measuring root length as a quantitative assay for drug sensitivity. The
      HPLC-purified extract, referred to as IVF3, reduced the growth of root vascular
      tissue compared to the control and vehicle control, and 50% as well as known
      angiogenesis inhibitors, VEGF receptor tyrosine kinase inhibitor and amiloride
      hydrochloride. Extracted compounds that were effective inhibitors of plant roots
      were assayed in Madin Darby canine kidney epithelial cells (MDCK) for toxicity,
      and in human umbilical vein endothelial cells (HUVEC) for their effect on
      migration. IVF3 was effective at limiting HUVEC migration in VEGF-stimulated
      cultures. In vivo video capture of intersegmental vessel circulation between 48
      and 72 h post fertilization in the developing vasculature of zebrafish embryos
      showed IVF3 also significantly reduced ISV functional circulation. This report
      demonstrates the anti-angiogenic effects of IVF3 extract in endothelial cells and
      in an intact vertebrate model for angiogenesis.

PMID- 21073865
TI  - Bystander effect in suicide gene therapy using immortalized neural stem cells
      transduced with herpes simplex virus thymidine kinase gene on medulloblastoma
      regression.
AB  - Medulloblastomas (MBs) are the most common malignant brain tumor in children. The
      current therapeutic strategies are ineffective against the infiltrative and
      disseminative nature of MBs in about one-third of patients. Based on studies
      which have revealed the tumor-tropic characteristic of neural stem cells (NSCs),
      we used an immortalized neural stem cell line C17.2 as a cellular therapeutic
      delivery system to evaluate the antitumor effect of herpes simplex virus
      thymidine kinase gene (HSVtk) on MBs. We first stably transfected the HSVtk gene
      into C17.2 cells to produce C17.2tk cells, and then mixed C17.2tk with the human
      MB cell line Daoy at various ratios supplemented with ganciclovir (GCV). Both in
      vitro and in vivo experiments yielded promising results. Even at a C17.2tk: Daoy
      ratio as low as 1:16, more than 25% cells were killed in vitro. In vivo co
      implantation study showed that when C17.2tk: Daoy ratio was 1:8, tumor growth
      inhibition was still evident and the mice had significantly prolonged survival.
      These results might partially be explained by the inherent tumor-tropic
      properties of NSCs and the bystander effect coupled with expression of connexin
      43 (Cx43) between C17.2tk and Daoy cells. Our study clearly showed for the first
      time that immortalized neural stem cells used as vectors to deliver HSVtk gene
      therapy have a strong tumoricidal effect on MBs.

PMID- 21073866
TI  - Multiple phospholipid substrates of phospholipase C/sphingomyelinase HR2 from
      Pseudomonas aeruginosa.
AB  - The activity of phospholipase C/sphingomyelinase HR(2) (PlcHR(2)) from
      Pseudomonas aeruginosa was characterized on a variety of substrates. The enzyme
      was assayed on liposomes (large unilamellar vesicles) composed of PC:SM:Ch:X
      (1:1:1:1; mol ratio) where X could be PE, PS, PG, or CL. Activity was measured
      directly as disappearance of substrate after TLC lipid separation. Previous
      studies had suggested that PlcHR(2) was active only on PC or SM. However we found
      that, of the various phospholipids tested, only PS was not a substrate for
      PlcHR(2). All others were degraded, in an order of preference PC>SM>CL>PE>PG.
      PlcHR(2) activity was sensitive to the overall lipid composition of the bilayer,
      including non-substrate lipids.

PMID- 21073867
TI  - Alcama mediates Edn1 signaling during zebrafish cartilage morphogenesis.
AB  - The zebrafish pharyngeal cartilage is derived from the pharyngeal apparatus, a
      vertebrate-specific structure derived from all three germ layers. Developmental
      aberrations of the pharyngeal apparatus lead to birth defects such as Treacher
      Collins and DiGeorge syndromes. While interactions between endoderm and neural
      crest (NC) are known to be important for cartilage formation, the full complement
      of molecular players involved and their roles remain to be elucidated. Activated
      leukocyte cell adhesion molecule a (alcama), a member of the immunoglobulin (Ig)
      superfamily, is among the prominent markers of pharyngeal pouch endoderm, but to
      date no role has been assigned to this adhesion molecule in the development of
      the pharyngeal apparatus. Here we show that alcama plays a crucial, non
      autonomous role in pharyngeal endoderm during zebrafish cartilage morphogenesis.
      alcama knockdown leads to defects in NC differentiation, without affecting NC
      specification or migration. These defects are reminiscent of the phenotypes
      observed when Endothelin 1 (Edn1) signaling, a key regulator of cartilage
      development is disrupted. Using gene expression analysis and rescue experiments
      we show that Alcama functions downstream of Edn1 signaling to regulate NC
      differentiation and cartilage morphogenesis. In addition, we also identify a role
      for neural adhesion molecule 1.1 (nadl1.1), a known interacting partner of Alcama
      expressed in neural crest, in NC differentiation. Our data shows that nadl1.1 is
      required for alcama rescue of NC differentiation in edn1(-/-) mutants and that
      Alcama interacts with Nadl1.1 during chondrogenesis. Collectively our results
      support a model by which Alcama on the endoderm interacts with Nadl1.1 on NC to
      mediate Edn1 signaling and NC differentiation during chondrogenesis.

PMID- 21073868
TI  - The influence of anthracosis and p16 ink4a gene aberrant methylation on small
      sized pulmonary adenocarcinoma.
AB  - AIMS: Anthracosis is the deposition of black dusty material in the pulmonary
      parenchyma. Previous reports showed anthracosis and p16(ink4a) gene aberrant
      methylation are closely related to the promotion and progression of small-sized
      pulmonary adenocarcinoma. In this study, we investigated the influence of
      anthracosis and p16(ink4a) gene aberrant methylation on clinical samples from
      patients with small-sized adenocarcinoma. METHODS AND RESULTS: DNA was bisulfite
      modified and methylation-specific PCR was performed to detect p16(ink4a) gene
      aberrant methylation; black dusty material was extracted from lung tissues.
      Anthracotic index (AI) was defined as the absolute absorbance by densitometry.
      The histopathological diagnosis was concluded according to Noguchi's
      classification for small-sized pulmonary adenocarcinoma. The mean AI and the
      frequency of p16(ink4a) gene aberrant methylation of heavy smokers were
      significantly higher than that of nonsmokers (P<0.01 andP<0.05, respectively).
      The frequency of p16(ink4a) gene aberrant methylation of early stage small-sized
      adenocarcinoma was lower than that of advanced and poorly differentiated, while
      p16(ink4a) protein expression level of early stage small-sized adenocarcinoma was
      significantly higher than that of poorly differentiated small-sized
      adenocarcinoma (P<0.05). CONCLUSIONS: AI and p16(ink4a) gene aberrant methylation
      may provide a potential universal biomarker for small-sized adenocarcinoma.

PMID- 21073869
TI  - Phylogenetic analysis and evolution of aromatic amino acid hydroxylase.
AB  - A study was performed to investigate the phylogenetic relationship among AAAH
      members and to statistically evaluate sequence conservation and functional
      divergence. In total, 161 genes were identified from 103 species. Phylogenetic
      analysis showed that well-conserved subfamilies exist. Exon-intron structure
      analysis showed that the gene structures of AAAH were highly conserved across
      some different lineage species, while some species-specific introns were also
      found. The dynamic distribution of ACT domain suggested one gene fusion event has
      occurred in eukaryota. Significant functional divergence was found between some
      subgroups. Analysis of the site-specific profiles revealed critical amino acid
      residues for functional divergence. This study highlights the molecular evolution
      of this family and may provide a starting point for further experimental
      verifications.

PMID- 21073870
TI  - Feedback regulation of Ras2 guanine nucleotide exchange factor (Ras2-GEF)
      activity of Cdc25p by Cdc25p phosphorylation in the yeast Saccharomyces
      cerevisiae.
AB  - Ras-GEF Cdc25p has been found to be hyperphosphorylated upon glucose addition.
      This work provides evidence indicating that PKA activity positively regulates the
      degree of Cdc25p phosphorylation, and that the intracellular association of
      Cdc25p and Ras2p is independent of PKA activity. In vitro experiments revealed
      that the Ras2-GEF activity of Cdc25p is inhibited by Cdc25p phosphorylation.
      These data suggest a negative feedback mechanism by which intracellular cAMP
      synthesis is inhibited by PKA through Cdc25p phosphorylation.

PMID- 21073871
TI  - Identification of an intracellular microdomain of the P2X7 receptor that is
      crucial in basolateral membrane targeting in epithelial cells.
AB  - We investigated membrane targeting of the P2X(7) receptor (P2X(7)R) in polarized
      epithelial cells using immunofluorescent confocal imaging. The wild-type receptor
      was targeted to the basolateral membrane, independently of adaptor protein MU1B.
      Deletion of the majority of the intracellular C-terminus, or the last 26 residues
      (P570-Y595), conferred targeting of the protein to the apical membrane. Alanine
      substitution in the microdomain P582-Q587 caused similar apical membrane
      targeting without major effect on the receptor function and surface expression.
      Our results show basolateral membrane targeting of the P2X(7)R in epithelial
      cells and that the intracellular C-terminal microdomain P582-Q587 is crucial in
      this process.

PMID- 21073872
TI  - Plant and animal type 2B Ca2+-ATPases: evidence for a common auto-inhibitory
      mechanism.
AB  - Plant auto-inhibited Ca(2+)-ATPase 8 (ACA8) and animal plasma membrane Ca(2+)
      ATPase 4b (PMCA4b) are representatives of plant and animal 2B P-type ATPases with
      a regulatory auto-inhibitory domain localized at the N- and C-terminus,
      respectively. To check whether the regulatory domain works independently of its
      terminal localization and if auto-inhibitory domains of different organisms are
      interchangeable, a mutant in which the N-terminus of ACA8 is repositioned at the
      C-terminus and chimeras in which PMCA4b C-terminus is fused to the N- or C
      terminus of ACA8 were analysed in the yeast mutant K616 devoid of endogenous
      Ca(2+)-ATPases. Results show that the regulatory function of the terminal domain
      is independent from its position in ACA8 and that the regulatory domain belonging
      to PMCA4b is able to at least partially auto-inhibit ACA8.

PMID- 21073874
TI  - Sexual arousal, is it for mammals only?
AB  - Sexual arousal has many dimensions and has consequently been defined in various
      ways. In humans, sexual arousal can be assessed based in part on verbal
      communication. In male non-human mammalian species, it has been argued that
      arousal can only be definitively inferred if the subject exhibits a penile
      erection in a sexual context. In non-mammalian species that lack an intromittent
      organ, as is the case for most avian species, the question of how to assess
      sexual arousal has not been thoroughly addressed. Based on studies performed in
      male Japanese quail, we argue that several behavioral or physiological
      characteristics provide suitable measures of sexual arousal in birds and probably
      also in other tetrapods. These indices include, the performance of appetitive
      sexual behavior in anticipation of copulation (although anticipation and arousal
      are not synonymous), the activation of specific brain area as identified by the
      detection of the expression of immediate early genes (fos, egr-1) or by 2
      deoxyglucose quantitative autoradiography, and above all, by the release of
      dopamine in the medial preoptic area as measured by in vivo dialysis. Based on
      these criteria, it is possible to assess in birds sexual arousal in its broadest
      sense but meeting the more restrictive definition of arousal proposed for male
      mammals (erection in an explicit sexual context) is and will probably remain
      impossible in birds until refinement of in vivo imaging techniques such fMRI
      allow us to match in different species, with and without an intromittent organ,
      the brain areas that are activated in the presence of specific stimuli.

PMID- 21073875
TI  - Mutant genetic background affects the functional rearrangement and kinetic
      properties of JMJD2b histone demethylase.
AB  - We have studied JMJD2b histone demethylase, which antagonizes H3K9me3 in the
      pericentromeric heterochromatin. In cells with a deficiency in the histone
      methyltransferase SUV39h, the level of full-length JMJD2b (JMJD2b-GFP-1086) at
      chromocenters was reduced, corresponding to a global decrease in JMJD2b and
      H3K9me3. In wild-type fibroblasts, the chromatin of ribosomal genes, which is
      dense with H3K9 methylation, lacked JMJD2b-GFP-1086, while mutant and truncated
      forms of JMJD2b densely occupied the nucleolar compartment. This implies that the
      PHD Zn-fingers and Tudor domains, which were removed in truncated JMJD2b, are
      responsible for the aberrant JMJD2b function. Intriguingly, the JMJD2b-GFP-1086
      level was significantly higher in tumor cell nucleoli. The kinetic properties of
      JMJD2b-GFP-1086 in the nucleoli and nucleoplasm of normal and tumor cells were
      similar; ~50% recovery of prebleached intensity was reached after <1 s. However,
      the mobile fraction of JMJD2b-GFP-1086 was increased in SUV39h-deficient cells.
      Similarly, the mobile fractions of mutant JMJD2b(1-424)H189A-GFP and truncated
      JMJD2b(1-424)GFP were greater than that measured for the full-length protein. We
      suggest that nucleoli are the site of an aberrant function of JMJD2b, the kinetic
      properties of which can be influenced by a mutant genetic background.

PMID- 21073873
TI  - Immunologic basis of graft rejection and tolerance following transplantation of
      liver or other solid organs.
AB  - Transplantation of organs between genetically different individuals of the same
      species causes a T cell-mediated immune response that, if left unchecked, results
      in rejection and graft destruction. The potency of the alloimmune response is
      determined by the antigenic disparity that usually exists between donors and
      recipients and by intragraft expression of proinflammatory cytokines in the early
      period after transplantation. Studies in animal models have identified many
      molecules that, when targeted, inhibit T-cell activation. In addition, some of
      these studies have shown that certain immunologic interventions induce
      transplantation tolerance, a state in which the allograft is specifically
      accepted without the need for chronic immunosuppression. Tolerance is an
      important aspect of liver transplantation, because livers have a unique
      microenvironment that promotes tolerance rather than immunity. In contrast to the
      progress achieved in inducing tolerance in animal models, patients who receive
      transplanted organs still require nonspecific immunosuppressant drugs. The
      development of calcineurin inhibitors has reduced the acute rejection rate and
      improved short-term, but not long-term, graft survival. However, long-term use of
      immunosuppressive drugs leads to nephrotoxicity and metabolic disorders, as well
      as manifestations of overimmunosuppression such as opportunistic infections and
      cancers. The status of pharmacologic immunosuppression in the clinic is therefore
      not ideal. We review recently developed therapeutic strategies to promote
      tolerance to transplanted livers and other organs and diagnostic tools that might
      be used to identify patients most likely to accept or reject allografts.

PMID- 21073876
TI  - Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase
      from Leishmania major.
AB  - Nucleotide sugars and the enzymes that are responsible for their synthesis are
      indispensable for the production of complex carbohydrates and, thus, for
      elaboration of a protective cellular coat for many organisms such as the
      protozoan parasite Leishmania. These activated sugars are synthesized de novo or
      derived from salvaged monosaccharides. In addition to UDP-glucose (UDP-Glc)
      pyrophosphorylase, which catalyzes the formation of UDP-Glc from substrates UTP
      and glucose-1-phosphate, Leishmania major and plants express a UDP-sugar
      pyrophosphorylase (USP) that exhibits broad substrate specificity in vitro. The
      enzyme, likely involved in monosaccharide salvage, preferentially generates UDP
      Glc and UDP-galactose, but it may also activate other hexose- or pentose-1
      phosphates such as galacturonic acid-1-phosphate or arabinose-1-phosphate. In
      order to gain insight into structural features governing the differences in
      substrate specificity, we determined the crystal structure of the L. major USP in
      the APO-, UTP-, and UDP-sugar-bound conformations. The overall tripartite
      structure of USP exhibits a significant structural homology to other
      nucleotidyldiphosphate-glucose pyrophosphorylases. The obtained USP structures
      reveal the structural rearrangements occurring during the stepwise binding
      process of the substrates. Moreover, the different product complexes explain the
      broad substrate specificity of USP, which is enabled by structural changes in the
      sugar binding region of the active site.

PMID- 21073877
TI  - Inhibiting beta-secretase activity in Alzheimer's disease cell models with single
      chain antibodies specifically targeting APP.
AB  - The Amyloid-beta (Abeta) peptide is produced from the amyloid precursor protein
      (APP) by sequential proteolytic cleavage of APP first by beta-secretase and then
      by gamma-secretase. beta-Site APP cleaving enzyme-1 (BACE-1) is the predominant
      enzyme involved in beta-secretase processing of APP and is a primary therapeutic
      target for treatment of Alzheimer's disease. While inhibiting BACE-1 activity has
      obvious therapeutic advantages, BACE-1 also cleaves numerous other substrates
      with important physiological activity. Thus, blanket inhibition of BACE-1
      function may have adverse side effects. We isolated a single chain variable
      fragment (scFv) from a human-based scFv yeast display library that selectively
      inhibits BACE-1 activity toward APP by binding the APP substrate at the
      proteolytic site. We selected the iBSEC1 scFv, since it recognizes the BACE-1
      cleavage site on APP but does not bind the adjacent highly antigenic N-terminal
      of Abeta, and thus it will target APP but not soluble Abeta. When added to 7PA2
      cells, a mammalian cell line that overexpresses APP, the iBSEC1 scFv binds APP on
      the cell surface, reduces toxicity induced by APP overexpression, and reduces
      both intracellular and extracellular Abeta levels by around 50%. Since the iBSEC1
      scFv does not contain the antibody F(c) region, this construct does not pose the
      risk of exacerbating inflammation in the brain as faced with full-length
      monoclonal antibodies for potential therapeutic applications.

PMID- 21073879
TI  - Distal-to-proximal NO conversion in hemoproteins: the role of the proximal
      pocket.
AB  - Hemoproteins play central roles in the formation and utilization of nitric oxide
      (NO) in cellular signaling, as well as in protection against nitrosative stress.
      Key to heme-nitrosyl function and reactivity is the Fe coordination number (5 or
      6). For (five-coordinate) 5c-NO complexes, the potential for NO to bind on either
      heme face exists, as in the microbial cytochrome c' from Alcaligenes xylosoxidans
      (AxCYTcp), which forms a stable proximal 5c-NO complex via a distal six
      coordinate NO intermediate and a putative dinitrosyl species. Strong parallels
      between the NO-binding kinetics of AxCYTcp, the eukaryotic NO sensor soluble
      guanylate cyclase, and the ferrocytochrome c/cardiolipin complex have led to the
      suggestion that a distal-to-proximal NO switch could contribute to the selective
      ligand responses in gas-sensing hemoproteins. The proximal NO-binding site in
      AxCYTcp is close to a conserved basic (Arg124) residue that is postulated to
      modulate NO reactivity. We have replaced Arg124 by five different amino acids and
      have determined high-resolution (1.07-1.40 A) crystallographic structures with
      and without NO. These, together with kinetic and resonance Raman data, provide
      new insights into the mechanism of distal-to-proximal heme-NO conversion,
      including the determinants of Fe-His bond scission. The Arg124Ala variant allowed
      us to determine the structure of an analog of the previously unobserved key 5c-NO
      distal intermediate species. The very high resolution structures combined with
      the extensive spectroscopic and kinetic data have allowed us to provide a fresh
      insight into heme reactivity towards NO, a reaction that is of wide importance in
      biology.

PMID- 21073878
TI  - Alternate states of proteins revealed by detailed energy landscape mapping.
AB  - What conformations do protein molecules populate in solution? Crystallography
      provides a high-resolution description of protein structure in the crystal
      environment, while NMR describes structure in solution but using less data. NMR
      structures display more variability, but is this because crystal contacts are
      absent or because of fewer data constraints? Here we report unexpected insight
      into this issue obtained through analysis of detailed protein energy landscapes
      generated by large-scale, native-enhanced sampling of conformational space with
      Rosetta@home for 111 protein domains. In the absence of tightly associating
      binding partners or ligands, the lowest-energy Rosetta models were nearly all
      <2.5 A C(alpha)RMSD from the experimental structure; this result demonstrates
      that structure prediction accuracy for globular proteins is limited mainly by the
      ability to sample close to the native structure. While the lowest-energy models
      are similar to deposited structures, they are not identical; the largest
      deviations are most often in regions involved in ligand, quaternary, or crystal
      contacts. For ligand binding proteins, the low energy models may resemble the apo
      structures, and for oligomeric proteins, the monomeric assembly intermediates.
      The deviations between the low energy models and crystal structures largely
      disappear when landscapes are computed in the context of the crystal lattice or
      multimer. The computed low-energy ensembles, with tight crystal-structure-like
      packing in the core, but more NMR-structure-like variability in loops, may in
      some cases resemble the native state ensembles of proteins better than individual
      crystal or NMR structures, and can suggest experimentally testable hypotheses
      relating alternative states and structural heterogeneity to function.

PMID- 21073880
TI  - Multi-timescale dynamics study of FKBP12 along the rapamycin-mTOR binding
      coordinate.
AB  - Drugs can affect function in proteins by modulating their flexibility. Despite
      this possibility, there are very few studies on how drug binding affects the
      dynamics of target macromolecules. FKBP12 (FK506 binding protein 12) is a prolyl
      cis-trans isomerase and a drug target. The immunosuppressant drug rapamycin
      exerts its therapeutic effect by serving as an adaptor molecule between FKBP12
      and the cell proliferation regulator mTOR (mammalian target of rapamycin). To
      understand the role of dynamics in rapamycin-based immunosuppression and to gain
      insight into the role of dynamics in the assembly of supramolecular complexes, we
      used (15)N, (13)C, and (2)H NMR spin relaxation to characterize FKBP12 along the
      binding coordinate that leads to cell cycle arrest. We show that sequential
      addition of rapamycin and mTOR leads to incremental rigidification of the FKBP12
      backbone on the picosecond-nanosecond timescale. Both binding events lead to
      perturbation of main-chain and side-chain dynamics at sites distal to the binding
      interfaces, suggesting tight coupling interactions dispersed throughout the
      FKBP12-rapamycin interface. Binding of the first molecule, rapamycin, quenches
      microsecond-millisecond motions of the FKBP12 80's loop. This loop provides much
      of the surface buried at the protein-protein interface of the ternary complex,
      leading us to assert that preorganization upon rapamycin binding facilitates
      binding of the second molecule, mTOR. Widespread microsecond-millisecond motions
      of the backbone persist in the drug-bound enzyme, and we provide evidence that
      these slow motions represent coupled dynamics of the enzyme and isomerization of
      the bound drug. Finally, the pattern of microsecond-millisecond dynamics reported
      here in the rapamycin complex is dramatically different from the pattern in the
      complex with the structurally related drug FK506. This raises the important
      question of how two complexes that are highly isomorphic based on high-resolution
      static models have such different flexibilities in solution.

PMID- 21073881
TI  - Structural insight into the expanded PCB-degrading abilities of a biphenyl
      dioxygenase obtained by directed evolution.
AB  - The biphenyl dioxygenase of Burkholderia xenovorans LB400 is a multicomponent
      Rieske-type oxygenase that catalyzes the dihydroxylation of biphenyl and many
      polychlorinated biphenyls (PCBs). The structural bases for the substrate
      specificity of the enzyme's oxygenase component (BphAE(LB400)) are largely
      unknown. BphAE(p4), a variant previously obtained through directed evolution,
      transforms several chlorobiphenyls, including 2,6-dichlorobiphenyl, more
      efficiently than BphAE(LB400), yet differs from the parent oxygenase at only two
      positions: T335A/F336M. Here, we compare the structures of BphAE(LB400) and
      BphAE(p4) and examine the biochemical properties of two BphAE(LB400) variants
      with single substitutions, T335A or F336M. Our data show that residue 336
      contacts the biphenyl and influences the regiospecificity of the reaction, but
      does not enhance the enzyme's reactivity toward 2,6-dichlorobiphenyl. By
      contrast, residue 335 does not contact biphenyl but contributes significantly to
      expansion of the enzyme's substrate range. Crystal structures indicate that
      Thr335 imposes constraints through hydrogen bonds and nonbonded contacts to the
      segment from Val320 to Gln322. These contacts are lost when Thr is replaced by
      Ala, relieving intramolecular constraints and allowing for significant movement
      of this segment during binding of 2,6-dichlorobiphenyl, which increases the space
      available to accommodate the doubly ortho-chlorinated congener 2,6
      dichlorobiphenyl. This study provides important insight about how Rieske-type
      oxygenases can expand substrate range through mutations that increase the
      plasticity and/or mobility of protein segments lining the catalytic cavity.

PMID- 21073882
TI  - Structure of human complement C8, a precursor to membrane attack.
AB  - Complement component C8 plays a pivotal role in the formation of the membrane
      attack complex (MAC), an important antibacterial immune effector. C8 initiates
      membrane penetration and coordinates MAC pore formation. High-resolution
      structures of C8 subunits have provided some insight into the function of the C8
      heterotrimer; however, there is no structural information describing how the
      intersubunit organization facilitates MAC assembly. We have determined the
      structure of C8 by electron microscopy and fitted the C8alpha-MACPF (membrane
      attack complex/perforin)-C8gamma co-crystal structure and a homology model for
      C8beta-MACPF into the density. Here, we demonstrate that both the C8gamma
      protrusion and the C8alpha-MACPF region that inserts into the membrane upon
      activation are accessible.

PMID- 21073883
TI  - Pathogenic mutations in antisense mitochondrial tRNAs.
AB  - Pathogenic mutations in mitochondrial tRNAs are 6.5 times more frequent than in
      other mitochondrial genes. This suggests that tRNA mutations perturb more than
      one function. A potential additional tRNA gene function is that of templating for
      antisense tRNAs. Pathogenic mutations weaken cloverleaf secondary structures of
      sense tRNAs. Analyses here show similar effects for most antisense tRNAs,
      especially after adjusting for associations between sense and antisense
      cloverleaf stabilities. These results imply translational activity by antisense
      tRNAs. For sense tRNAs Ala and Ser UCN, pathogenicity associates as much with
      sense as with antisense cloverleaf formation. For tRNA Pro, pathogenicity seems
      associated only with antisense, not sense tRNA cloverleaf formation.
      Translational activity by antisense tRNAs is expected for the 11 antisense tRNAs
      processed by regular sense RNA maturation, those recognized by their cognate
      amino acid's tRNA synthetase, and those forming relatively stable cloverleaves as
      compared to their sense counterpart. Most antisense tRNAs probably function
      routinely in translation and extend the tRNA pool (extension hypothesis); others
      do not (avoidance hypothesis). The greater the expected translational activity of
      an antisense tRNA, the more pathogenic mutations weaken its cloverleaf secondary
      structure. Some evidence for RNA interference, a more classical role for
      antisense tRNAs, exists only for tRNA Ser UCN. Mutation pathogenicity probably
      frequently results from a mixture of effects due to sense and antisense tRNA
      translational activity for many mitochondrial tRNAs. Genomic studies should
      routinely explore for translational activity by antisense tRNAs.

PMID- 21073884
TI  - Rescue effects in radiobiology: unirradiated bystander cells assist irradiated
      cells through intercellular signal feedback.
AB  - Mammalian cells respond to ionization radiation by sending out extracellular
      signals to affect non-irradiated neighboring cells, which is referred to as
      radiation induced bystander effect. In the present paper, we described a
      phenomenon entitled the "rescue effects", where the bystander cells rescued the
      irradiated cells through intercellular signal feedback. The effect was observed
      in both human primary fibroblast (NHLF) and cancer cells (HeLa) using two-cell co
      culture systems. After co-culturing irradiated cells with unirradiated bystander
      cells for 24h, the numbers of 53BP1 foci, corresponding to the number of DNA
      double-strand breaks in the irradiated cells were less than those in the
      irradiated cells that were not co-cultured with the bystander cells (0.78+/
      0.04foci/cell vs. 0.90+/-0.04foci/cell) at a statistically significant level.
      Similarly, both micronucleus formation and extent of apoptosis in the irradiated
      cells were different at statistically significant levels if they were co-cultured
      with the bystander cells. Furthermore, it was found that unirradiated normal
      cells would also reduce the micronucleus formation in irradiated cancer cells.
      These results suggested that the rescue effects could participate in repairing
      the radiation-induced DNA damages through a media-mediated signaling feedback,
      thereby mitigating the cytotoxicity and genotoxicity of ionizing radiation.

PMID- 21073885
TI  - The alpha7 nicotinic acetylcholine receptor and the acute stress response:
      maternal genotype determines offspring phenotype.
AB  - alpha7 Nicotinic acetylcholine receptors (alpha7nAchRs) modulate immune
      activation by suppressing production of pro-inflammatory cytokines in peripheral
      immune cells. alpha7nAchRs also modulate inhibitory output in the hippocampus,
      which provides input to key circuits of the HPA axis. Therefore, the alpha7
      nicotinic acetylcholine receptor gene (CHRNA7) may be associated with cortisol
      stress response. Polymorphisms in the CHRNA7 promoter decrease its expression and
      may dampen the cholinergic response, leading to an increase in inflammation.
      Increased inflammation may change the intrauterine environment, altering
      neuroendocrine development in the offspring. Maternal CHRNA7 genotype could
      affect an offspring's HPA regulation via reprogramming in utero. Patients with
      allergic disorders have a differential cortisol response to stress. This study
      utilized samples collected from a cohort of 198 adolescents in a previous study
      of atopic disorders, who demonstrated a disturbance in HPA response associated
      with atopy. Salivary cortisol samples collected from the adolescents after a
      series of laboratory procedures and DNA samples collected from the adolescents
      and their parents were used for further analysis. DNA samples were genotyped for
      allelic variation in the CHRNA7 promoter. Genetic association analyses with the
      cortisol levels were performed in the adolescents. Maternal genotype influences
      were investigated for the CHRNA7 gene. We also included maternal and child atopy
      diagnosis as covariates in determining cortisol levels and tested for association
      of CHRNA7 to atopy. Polymorphisms in the CHRNA7 promoter were associated with
      lower cortisol levels after a small laboratory stress. Our findings also show
      that although the child's CHRNA7 genotype affects stress response, the maternal
      genotype has a stronger influence on cortisol release after stress in male
      offspring. These effects were independent of atopy status.

PMID- 21073886
TI  - Abolished circadian rhythm of salivary cortisol in elite artistic gymnasts.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of intensive
      physical exercise and acute psychological stress during high level athletic
      competition as reflected on the levels of salivary cortisol in elite artistic
      gymnasts (AGs). DESIGN: The study included 239 AGs (142 females-97 males) who
      participated in the European Championship of Gymnastics in 2006 and 81
      adolescents (40 females-41 males), matched for age, as controls. All athletes
      participated voluntarily in all or parts of the study, providing samples or data
      for each of the variables measured. Height, weight, body fat, lean body mass
      (LBM), bone age and Tanner stage of puberty were assessed and data concerning the
      time of thelarche, adrenarche and menarche as well as, the onset and the
      intensity (hours per week) of training were obtained. METHODS: Saliva samples
      were collected, the morning before training and in the afternoon shortly after
      the competition. From controls, the saliva samples were collected in the morning.
      Cortisol concentrations were measured using a chemiluminescence method. Acute
      stress was assessed using a questionnaire designed for the study. RESULTS: No
      difference was found between morning and afternoon salivary cortisol levels in
      both male and female AGs (females: AM: 15.45+/-7.45nmol/l vs PM: 15.73+/
      9.38nmol/l; males: AM: 10.21+/-5.52nmol/l vs PM: 9.93+/-13.8nmol/l, p>0.05).
      Female AGs presented higher levels of morning salivary cortisol than female
      controls (p<0.05). Both male and female AGs had higher degree of psychological
      stress in comparison with controls (p<0.001, p<0.013, respectively). Female AGs
      had higher morning and afternoon salivary cortisol levels (p<0.01, p<0.01,
      respectively) and higher degree of stress (p<0.003) than males. CONCLUSIONS: In
      elite AGs the diurnal rhythm of salivary cortisol has been abolished, probably
      due to the strenuous training and competition conditions. Female AGs presented
      higher levels of morning salivary cortisol and psychological stress compared to
      both male AGs and female controls. The long term consequences of these
      modifications of the HPA axis remain to be elucidated.

PMID- 21073887
TI  - First report about saxitoxins in freshwater fish Hoplias malabaricus through
      trophic exposure.
AB  - Cyanobacterial waterblooms, such as the saxitoxin (STX) producer
      Cylindrospermopsis raciborskii, have been a worldwide concern in environmental
      health. However, the bioaccumulation of this neurotoxin in the trophic chain is
      not completely known. The aim of the present work was to evaluate STX
      bioaccumulation through chemical analyses and the toxic and trophic effects using
      biomarkers in the tropical freshwater fish Hoplias malabaricus. They were fed
      once every five days with Astyanax sp. before being subjected to intraperitoneal
      inoculation with STX extract (0.08 MUg/100 g) obtained by lysis of toxic C.
      raciborskii strain (T3). After 20 days the brain was collected for
      acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT),
      glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione (GSH),
      lipoperoxidation (LPO), protein carbonylation (PCO), and comet assay analysis.
      The muscle was collected for STX chemical analysis. The activities of SOD and
      concentrations of PCO and LPO increased. The CAT, GST, and GPx activities
      decreased. Genotoxicity was observed in the experimental group. STX was not
      detected in muscle samples. Thus, an oxidative stress was observed in the brain,
      leading to the damage of lipids, proteins, and DNA. The mechanism of action of
      the neurotoxin in this subchronic exposure suggests an apoptotic cellular
      process.

PMID- 21073888
TI  - "Insularin, a disintegrin from Bothrops insularis venom: inhibition of platelet
      aggregation and endothelial cell adhesion by the native and recombinant GST
      insularin proteins".
AB  - Insularin (INS) was obtained from Bothrops insularis venom by reversed-phase high
      performance liquid chromatography using a C(18) column and characterized as a
      disintegrin by peptide mass fingerprint and inhibition of ADP-induced platelet
      aggregation. A cDNA coding for P-II a metalloproteinase/disintegrin was cloned
      from a cDNA library from B. insularis venom glands. The deduced protein sequence
      possesses 73 amino acid residues, including the N-terminal, internal peptides of
      native insularin, the ARGDNP-sequence and 12 cysteines in a conserved alignment.
      This cDNA fragment was subcloned in the pGEX-4T-1 vector and expressed in a
      prokaryotic expression system as a fusion protein with glutathione S-transferase
      (GST-INS). Both native and recombinant insularin inhibited ADP-induced platelet
      aggregation and endothelial cells (HUVEC) adhesion with similar activities
      indicating that GST-INS folded correctly and preserved the integrin-binding loop.
      Insularin may be a tool in studies that involve platelets and endothelial cell
      adhesion dependent on alphaIIbeta3 and alphavbeta3 integrins.

PMID- 21073889
TI  - Spatial judgments in patients with retinitis pigmentosa.
AB  - Previous investigations into cortical plasticity in the presence of ocular
      disease have focused on central retinal damage. Perceptually, patients often
      report distortions of visual space which can be partially explained by perceptual
      filling-in. The mechanisms involved could also apply to peripheral field loss.
      Spatial interval discrimination was tested in 28 retinitis pigmentosa (RP)
      patients and a control group. When stimuli were presented to both hemispheres,
      bias did not differ whereas threshold was poorer in RP patients. When presenting
      the task to only one hemifield, bias was related to field asymmetry, but only in
      the left visual field, r(2)=.59. Brain laterality may be an important factor when
      examining changes in cortical function in response to peripheral system damage.

PMID- 21073890
TI  - Flupirtine antinociception in the rat orofacial formalin test: an analysis of
      combination therapies with morphine and tramadol.
AB  - Combination therapy with two drugs is a straightforward strategy to improve the
      risk-benefit ratio of analgesic treatments. Flupirtine is a non-opioid analgesic
      drug acting via the enhancement of so-called M currents, associated to Kv7
      potassium channels in the central nervous system. In this study we used the
      orofacial formalin test as a model of acute inflammatory pain in the rat;
      putative synergistic interactions between flupirtine and morphine or tramadol,
      given in various combinations, were investigated. We found that flupirtine exerts
      antinociception in the second phase of the test, whereas morphine and tramadol
      induced analgesia both in the first and in the second phase. An isobolographic
      analysis of data was carried out, showing a synergistic interaction between
      flupirtine and morphine, as well as between flupirtine and tramadol, in the
      second phase of the test. Conversely, in the first phase of the test only a
      single combination of morphine plus flupirtine, but not any of the combinations
      of tramadol and flupirtine, resulted in a synergistic interaction. Our data
      clearly indicate that flupirtine enhances in a synergistic manner the acute
      antinociceptive effects exerted by opioids in this paradigm.

PMID- 21073891
TI  - WITHDRAWN: Galectin-1 (OfGLec-1) from rock bream (Oplegnathus fasciatus):
      Identification, characterization, gene expression and functional properties.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21073892
TI  - Molecular responses of Ostrea edulis haemocytes to an in vitro infection with
      Bonamia ostreae.
AB  - Bonamiosis due to the parasite Bonamia ostreae is a disease affecting the flat
      oyster Ostrea edulis. B. ostreae is a protozoan, affiliated to the order of
      haplosporidia and to the cercozoan phylum. This parasite is mainly intracellular,
      infecting haemocytes, cells notably involved in oyster defence mechanisms.
      Suppression subtractive hybridisation (SSH) was carried out in order to identify
      oyster genes differentially expressed during an infection of haemocytes with B.
      ostreae. Forward and reverse banks allowed obtaining 1104 and 1344 clones
      respectively, among which 391 and 480 clones showed a differential expression
      between both tested conditions (haemocytes alone versus haemocytes in contact
      with parasites). ESTs of interest including genes involved in cytoskeleton,
      respiratory chain, detoxification membrane receptors, and immune system were
      identified. The open reading frames of two selected genes (galectin and IRF-like)
      were completely sequenced and characterized. Real time PCR assays were developed
      to study the relative expression of candidate ESTs during an in vitro infection
      of haemocytes by live and dead parasites. Haemocyte infection with B. ostreae
      induced an increased expression of omega glutathione S-transferase (OGST),
      superoxide dismutase (SOD), tissue inhibitor of metalloproteinase (TIMP),
      galectin, interferon regulatory factor (IRF-like) and filamin genes.

PMID- 21073893
TI  - Performance of a nurse-led paediatric point of care service for respiratory
      syncytial virus testing in secondary care.
AB  - OBJECTIVES: To evaluate respiratory syncytial virus (RSV)-point-of-care-testing
      (POCT) performance among paediatric patients with respiratory symptoms, using the
      BinaxNOW((r)) RSV assay performed by trained nurses on the paediatric ward, and
      compare results with those obtained by real-time polymerase chain reaction (PCR).
      METHODS: Four paediatric nurses were trained and certified in using RSV-POCT.
      Between October 2008 and March 2009, all hospitalised children below 5 years of
      age presenting with a suspected RSV infection had nasopharyngeal swabs (NPS)
      tested by RSV-POCT by the nurses and a real-time PCR targeting common respiratory
      viruses by laboratory staff. RESULTS: Among 159 NPS, 21 (13.2%) were RSV-POCT
      positive and 138 (86.8%) negative. All 21 RSV-POCT positive samples were positive
      by PCR, yielding a specificity of 100% (95% CI 95.7%, 100.0%). Of 138 RSV-POCT
      negative samples, 30 (21.7%) were RSV positive by PCR (sensitivity 41.2%; 95% CI:
      27.9%, 55.8%). The positive and negative predictive values for RSV-POCT were 100%
      (95% CI 80.8%, 100.0%) and 78.3% (95% CI 70.3%, 84.6%) respectively. Other
      respiratory viruses were detected in 52/138 (39.9%) NPS. CONCLUSIONS: A POCT for
      RSV run by trained nurses can be used reliably as a first screening step in
      symptomatic children. Negative samples should be analysed for RSV and other
      respiratory pathogens by real-time PCR.

PMID- 21073894
TI  - Rifaximin intake leads to emergence of rifampin-resistant staphylococci.
AB  - OBJECTIVES: Rifaximin is a poorly absorbed non-systemic antimicrobial agent used
      in various gastrointestinal disorders. Rifampin is pivotal for the treatment of
      staphylococcal foreign body infections and resistance develops rapidly during
      monotherapy. The close structural relation of rifaximin to rifampin may lead to
      cross-resistance. The aim of our study was to determine whether rifampin
      resistance emerges in human skin staphylococci during or after oral intake of
      rifaximin. METHODS: Rifampin resistance of skin staphylococci in healthy
      volunteers during and after intake of rifaximin was determined by E-Test.
      RESULTS: Seven out of eleven volunteers developed rifampin-resistant
      staphylococci after intake of rifaximin. A total of eleven rifampin-resistant and
      three rifampin-intermediate staphylococcal isolates were found. Before or during
      intake no resistant isolate was detected. Shortly after discontinuation the
      rifampin-resistant strains were primarily isolated from the perianal skin, a few
      weeks later they were found more frequently on the skin of the hands and lower
      arms. CONCLUSION: Our data show that rifampin-resistant staphylococci emerge
      after intake of rifaximin. Since rifampin resistance is associated with treatment
      failure in staphylococcal foreign body infections, we conclude that rifaximin
      should be avoided in patients at risk for these infections.

PMID- 21073895
TI  - An artificial neural network improves the non-invasive diagnosis of significant
      fibrosis in HIV/HCV coinfected patients.
AB  - OBJECTIVE: To develop an artificial neural network to predict significant
      fibrosis (F>=2) (ANN-SF) in HIV/Hepatitis C (HCV) coinfected patients using
      clinical data derived from peripheral blood. METHODS: Patients were randomly
      divided into an estimation group (217 cases) used to generate the ANN and a test
      group (145 cases) used to confirm its power to predict F>=2. Liver fibrosis was
      estimated according to the METAVIR score. RESULTS: The values of the area under
      the receiver operating characteristic curve (AUC-ROC) of the ANN-SF were 0.868 in
      the estimation set and 0.846 in the test set. In the estimation set, with a cut
      off value of <0.35 to predict the absence of F>=2, the sensitivity (Se),
      specificity (Sp), and positive (PPV) and negative predictive values (NPV) were
      94.1%, 41.8%, 66.3% and 85.4% respectively. Furthermore, with a cut-off value of
      >0.75 to predict the presence of F>=2, the ANN-SF provided Se, Sp, PPV and NPV of
      53.8%, 94.9%, 92.8% and 62.8% respectively. In the test set, with a cut-off value
      of <0.35 to predict the absence of F>=2, the Se, Sp, PPV and NPV were 91.8%,
      51.7%, 72.9% and 81.6% respectively. Furthermore, with a cut-off value of >0.75
      to predict the presence of F>=2, the ANN-SF provided Se, Sp, PPV and NPV of
      43.5%, 96.7%, 94.9% and 54.7% respectively. CONCLUSION: The ANN-SF accurately
      predicted significant fibrosis and outperformed other simple non-invasive indices
      for HIV/HCV coinfected patients. Our data suggest that ANN may be a helpful tool
      for guiding therapeutic decisions in clinical practice concerning HIV/HCV
      coinfection.

PMID- 21073896
TI  - The significance of very low-level viraemia detected by sensitive viral load
      assays in HIV infected patients on HAART.
AB  - OBJECTIVES: Viral load (VL) measurement is critical for monitoring the
      effectiveness of highly active antiretroviral therapy (HAART). HAART aims to
      maintain plasma HIV RNA at undetectable levels. A VL <50 copies/ml was previously
      considered undetectable. After introducing more sensitive assays many patients
      with VL <50 copies/ml were found to have very low-level viraemia (VLLV), defined
      as a detectable VL <40 copies/ml. This study aimed to determine the significance
      of VLLV. METHODS: This retrospective case-control study included 69 individuals
      on HAART with VLLV. Immunological and virological outcomes over 36 months were
      compared to those of 70 well-matched controls with persistently undetectable VL.
      RESULTS: We detected no significant association between VLLV and the development
      of virological failure or inferior immunological outcomes. However, individuals
      with VLLV were significantly less likely to achieve subsequent sustained
      virological suppression (VL <50 copies/ml, p<0.001), including completely
      undetectable suppression (undetectable VL <40 copies/ml, p=0.002). CONCLUSIONS:
      The significance of VLLV has been uncertain. Our results clearly suggest that
      VLLV is predictive of future suboptimal virological control, particularly a
      reduced likelihood of achieving virological suppression. Further work should
      confirm our findings and evaluate strategies for managing VLLV in HAART-treated
      patients.

PMID- 21073897
TI  - Regulation of stem cell pluripotency and differentiation by G protein coupled
      receptors.
AB  - Stem cell-based therapeutics have the potential to effectively treat many
      terminal and debilitating human diseases, but the mechanisms by which their
      growth and differentiation are regulated are incompletely defined. Recent data
      from multiple systems suggest major roles for G protein coupled receptor (GPCR)
      pathways in regulating stem cell function in vivo and in vitro. The goal of this
      review is to illustrate common ground between the growing field of stem cell
      therapeutics and the long-established field of G protein coupled receptor
      signaling. Herein, we briefly introduce basic stem cell biology and discuss how
      several conserved pathways regulate pluripotency and differentiation in mouse and
      human stem cells. We further discuss general mechanisms by which GPCR signaling
      may impact these pluripotency and differentiation pathways, and summarize
      specific examples of receptors from each of the major GPCR subfamilies that have
      been shown to regulate stem cell function. Finally, we discuss possible
      therapeutic implications of GPCR regulation of stem cell function.

PMID- 21073898
TI  - The role of Natural Killer cells in the pathogenesis of rheumatoid arthritis:
      major contributors or essential homeostatic modulators?
AB  - Natural Killer (NK) cells are lymphocytes of the innate immune system, originally
      described by their capacity to control tumour cells and eliminate virus-infected
      cells. However accumulating evidence suggests that NK cells can interact with
      various components of the immune system and play a critical role in autoimmune
      diseases by limiting or exacerbating immune responses. Rheumatoid arthritis is a
      chronic inflammatory disease characterised by joint inflammation and cartilage
      and bone destruction. NK cells are enriched within the joints of patients with
      rheumatoid arthritis but how they contribute to disease pathology is currently
      not fully elucidated. This review will outline the current understanding of NK
      cell biology and how these cells may modulate disease pathogenesis in rheumatoid
      arthritis through interactions with other immune cells.

PMID- 21073899
TI  - DNA vaccine expressing repeated carcinoembryonic antigen (CEA)(625-667) induces
      strong immunity in mice.
AB  - The efficacy of immunization with DNA plasmids for single truncated
      carcinoembryonic antigen (CEA) peptide or triple repeated CEA peptides in mice
      was evaluated. A DNA fragment the truncated CEA gene (nucleotide 625-667)
      encoding two helper T lymphocyte (HTL) epitopes was amplified by PCR and cloned
      for generating recombinant plasmids for single CEA(625-667) (pcDNA-CEA(625-667))
      or triple CEA(625-667) (pcDNA-triCEA(625-667)), respectively. Subsequently,
      groups of BALB/c female mice were intramuscularly injected with pcDNA-CEA(625
      667,) pcDNA-triCEA(625-667) or control pcDNA3.0 vector, respectively. Ten days
      after the last immunization, the frequency of splenic CD4(+) and CD8(+) T cells
      in the mice was determined by flow cytometry. The antigen-specific proliferation
      of splenic T cells and cytokine production ex vivo were analyzed by (3)H-TdR
      uptake and cytokine ELISA, respectively. The levels of serum antibodies against
      CEA in the mice were detected by Western blot and ELISA. Although immunization
      with plasmid for the CEA(625-667) peptide(s) did not alter the frequency of
      CD4(+) and CD8(+) T cells in mice, vaccination with plasmid for CEA peptide
      induced strong antigen-specific T cell proliferation, particularly for the
      plasmid encoding the triple-repeated CEA peptides, accompanied by significantly
      elevated levels of IFN-gamma secreted by T cells from the mice immunized with
      triple-repeated peptides. Furthermore, immunization with the plasmid for CEA
      peptide stimulated higher levels of antigen-specific antibody responses in mice.
      Vaccination with the plasmid for the triple repeated CEA peptides induced
      stronger Th1 responses. Our findings may be useful for the development of
      effective DNA vaccine for the immunotherapy of cancer.

PMID- 21073900
TI  - Real-time TaqMan RT-PCR for detection of maize chlorotic mottle virus in maize
      seeds.
AB  - Maize chlorotic mottle virus (MCMV) causes corn lethal necrosis disease, and can
      be transmitted through infected maize seeds. It remains a challenge to detect
      this virus in the seeds to prevent its introduction and infection. For this
      purpose, a real-time TaqMan RT-PCR procedure for efficient detection of MCMV was
      developed. The sensitivity of the method was 4 fg of total RNA or 25 copies of
      RNA transcripts, which was approximately ten-fold higher than conventional RT-PCR
      gel electrophoresis method. The successful detection of MCMV in maize seeds
      suggested the feasibility of this procedure for routine testing.

PMID- 21073901
TI  - Engineering recombinant poxviruses using a compact GFP-blasticidin resistance
      fusion gene for selection.
AB  - Recombinant poxviruses are important tools for research and some are candidate
      vaccines. To make these viruses a simple, small vector that can be used to
      engineer multiple strains of vaccinia virus and other model poxviruses, including
      ectromelia virus is of value. Here a set of plasmids and methods for making these
      viruses that uses an enhanced green fluorescent protein-blasticidin resistance
      (GFP-bsd) fusion gene as a transient selectable marker are described. This gene
      is smaller than any of the bi-functional selection markers used previously. The
      versatility of the method across different poxviruses is demonstrated by
      engineering changes into multiple loci of the WR and Modified Vaccinia Ankara
      (MVA) strains of vaccinia virus and also ectromelia virus. Finally, a set of
      vaccinia virus sequences for directing homologous recombination that are very
      highly conserved was designed and tested. These sequences allow a single plasmid
      to be used to insert a transgene into multiple strains of the virus.

PMID- 21073902
TI  - Development of a minor groove binder assay for real-time one-step RT-PCR
      detection of swine vesicular disease virus.
AB  - The design and development of a 5' conjugated minor groove binder (MGB) probe
      real-time RT-PCR assay are described for rapid, sensitive and specific detection
      of swine vesicular disease virus (SVDV) RNA. The assay is designed to target the
      2C gene of the SVDV genome and is capable of detecting 2*10(2) copies of an RNA
      standard per reaction. It does not detect any of the other RNA viruses that cause
      vesicular disease in pigs, or the human enterovirus, Coxsackie B5 virus (CVB5)
      which is closely related antigenically to SVDV. The linear range of this test was
      from 2*10(2) to 2*10(8) copies/MUl. The assay is rapid and can detect SVDV RNA in
      just over 3.5 h including the time required for nucleic acid extraction. The
      development of this assay provides a useful tool for the differential diagnosis
      of SVD or for the detection of SVDV in research applications. This study
      demonstrates the suitability of MGB probes as a real-time PCR chemistry for the
      diagnosis of swine vesicular disease.

PMID- 21073903
TI  - Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of
      dengue virus infection in vitro and in vivo.
AB  - Cellular alpha-glucosidases I and II are enzymes that sequentially trim the three
      terminal glucoses in the N-linked oligosaccharides of viral envelope
      glycoproteins. This process is essential for the proper folding of viral
      glycoproteins and subsequent assembly of many enveloped viruses, including dengue
      virus (DENV). Imino sugars are substrate mimics of alpha-glucosidases I and II.
      In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9
      78 and CM-10-18, are potent inhibitors of both alpha-glucosidases I and II in
      vitro and in treated animals, and efficiently inhibit DENV infection of cultured
      human cells. Pharmacokinetic studies reveal that both compounds are well
      tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic
      properties and bioavailability in mice. Moreover, we showed that oral
      administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in
      mice. Interestingly, while treatment of DENV infected mice with ribavirin alone
      did not reduce the viremia, combination therapy of ribavirin with sub-effective
      dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as
      indicated by a profound reduction of the viremia. Our findings thus suggest that
      combination therapy of two broad-spectrum antiviral agents may provide a
      practically useful approach for the treatment of DENV infection.

PMID- 21073904
TI  - Extinction of drug seeking.
AB  - Drug seeking behavior can be reduced or inhibited via extinction. The brain
      mechanisms for extinction of drug seeking are poorly understood but are of
      significant interest because of their potential to identify novel approaches that
      promote abstinence from drug taking. Here we review recent literature on the
      neural mechanisms for extinction in drug self-administration paradigms. First, we
      consider the brain regions important for extinction of drug seeking. Functional
      inactivation studies have identified infralimbic prefrontal cortex, nucleus
      accumbens shell, as well as medial dorsal hypothalamus in the expression of
      extinction of drug seeking. These structures have been implicated in extinction
      expression across several reinforcers including cocaine, heroin, and alcohol.
      Second, we consider molecular studies which show that extinction training is
      associated with plasticity in glutamatergic signaling in both nucleus accumbens
      shell and core, and that this training may reverse or ameliorate the
      neuroadaptations produced by chronic drug exposure and spontaneous withdrawal.
      Finally, we consider the neural circuitry for extinction of drug seeking.
      Functional disconnection and neuroanatomical tracing studies show that extinction
      expression depends, at least in part, on cortico-striatal-hypothalamic and
      cortico-hypothalalmic-thalamic pathways. Moreover, they indicate that the
      expression of extinction and reinstatement of drug seeking may depend on parallel
      pathways that converge within lateral hypothalamus and paraventricular thalamus.

PMID- 21073905
TI  - Drug treatment and familiar music aids an attention shift from vision to
      somatosensation in Parkinson's disease on the reach-to-eat task.
AB  - Sensory control of the natural skilled movement of reaching for a food target to
      eat (reach-to-eat) is closely coupled to the successive phases of the movement.
      Control subjects visually fixate the target from hand movement onset to the point
      that the digits contact the food, at which point they look away. This
      relationship between sensory attention and limb movement suggests that whereas
      limb advance is under visual control, grasping, limb withdrawal, and releasing
      the food to the mouth is guided by somatosensation. The pattern of sensory
      control is altered in Parkinson's disease (PD). PD subjects may visually fixate
      the target for longer durations prior to movement initiation, during the grasp,
      and during the initial portion of hand withdrawal suggesting that vision
      compensates for a somatosensory impairment. Because both medication and listening
      to favorite musical pieces have been reported to normalize some movements in
      subjects with PD, the present study compared the effect of medication and
      listening to preferred musical pieces on sensory attention shifts from vision to
      somatosensation during the reach-to-eat movement. Biometric measures of eye
      movement and the movement of the reaching limb were collected from PD subjects
      and aged-matched control subjects in four conditions in their own homes: off
      medication, off medication with music, on medication, and on medication with
      music. Unmedicated PD subjects were slower to visually disengage the target after
      grasping it. Their disengage latency was shortened by both music and medication.
      Medication and music did not improve other aspects of reaching, including
      reaching duration and the ratings of the movement elements of limb advance,
      grasping, and limb withdrawal. The results are discussed in relation to the idea
      that one way in which medication and music may aid movement in PD by normalizing
      somatosensory control of forelimb movement thus reducing compensatory visual
      monitoring.

PMID- 21073906
TI  - Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide
      evidences for a role on the oxidative stress response.
AB  - Components of the DNA mismatch repair (MMR) pathway are major players in
      processes known to generate genetic diversity, such as mutagenesis and DNA
      recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas
      disease has a highly heterogeneous population, composed of a pool of strains with
      distinct characteristics. Studies with a number of molecular markers identified
      up to six groups in the T. cruzi population, which showed distinct levels of
      genetic variability. To investigate the molecular basis for such differences, we
      analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed
      the existence of distinct isoforms of this protein. Here we compared cell
      survival rates after exposure to genotoxic agents and levels of oxidative stress
      induced DNA in different parasite strains. Analyses of msh2 mutants in both T.
      cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the
      response to various DNA damaging agents. The results suggest that the distinct
      MSH2 isoforms have differences in their activity. More importantly, they also
      indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite
      response to oxidative stress through a novel mitochondrial function that may be
      conserved in T. brucei.

PMID- 21073907
TI  - Functional analysis of novel aquaporins from Fasciola gigantica.
AB  - Fascioliasis, caused by liver flukes of the genus Fasciola, is an important
      disease of ruminants. In order to identify a potential new drug target we have
      studied aquaporin (AQP) in Fasciola gigantica. AQPs facilitate the transport of
      water, glycerol and other small solutes across biological membranes. The
      structure, function, and pathology of AQPs have been extensively studied in
      mammals but data for AQPs from trematodes is still limited. In the present study,
      we have functionally characterized two closely related AQP isoforms, FgAQP-1 and
      FgAQP-2, from the trematode F. gigantica. Immunohistochemical analysis located
      the FgAQPs in the tegumental cells, their processes and the tegument itself. In
      addition, they were present in the epithelial linings of testes and ovary.
      Expression in Xenopus oocytes of these FgAQPs increased osmotic water
      permeability 3-4-fold but failed to increase glycerol and urea permeability. AQPs
      have two highly conserved NPA motifs that are important for the function of the
      channel pore. In FgAQP-1 and FgAQP-2 the first NPA motif is changed to TAA.
      Substitution of Thr with Asn in the TAA motif of FgAQP-1 increased its water
      permeability twofold but did not affect urea and glycerol impermeability while
      the substitution at the pore mouth of Cys204 by Tyr caused loss of water
      permeability. In addition, the FgAQPs did not increase methylamine and ammonia
      permeability after expression in yeast. In comparison to rat AQP-1 the described
      FgAQPs showed low water permeability and further in vivo analyses are necessary
      to determine their contribution to osmoregulation in Fasciola.

PMID- 21073908
TI  - Protective role of ghrelin against carbon tetrachloride (CCl4)-induced
      coagulation disturbances in rats.
AB  - Recent data indicate that ghrelin has protective effects in different organs and
      cell types including the pancreas, heart, and gastrointestinal tract. The purpose
      of this study was to determine whether ghrelin plays a protective role against
      CCl4-induced coagulation disturbances in rats. Fourty male Sprague-Dawley rats
      were equally divided into four groups including group 1 (1 ml physiological
      saline s.c., for 5 days), group 2 (CCl4, i.p., single dose of 1.6 g/kg), group 3
      (ghrelin, s.c., 10 nmol/kg/day, for 5 days) and group 4 (ghrelin, 10 nmol/kg/day,
      for 5 days plus CCl4, i.p., single dose of 1.6 g/kg on the 5th day). Fibrinogen
      level, activated partial thromboplastin time (aPTT), prothrombin time (PT),
      platelet counts and alanine transaminase (ALT) activity were evaluated. The
      values of PT, aPTT and ALT activity were increased (p < 0.05), while fibrinogen
      level was decreased (p < 0.05) due to CCl4 treatment alone. Pre-treatment with
      ghrelin prior to the administration of CCl4 reduced (p < 0.05) PT, aPTT and ALT
      values and increased (p < 0.05) fibrinogen level when compared with CCl4-treated
      only group. The results of this study suggest that exogenously administered
      ghrelin may play a protective role against CCl4-induced coagulation disturbances
      in rats.

PMID- 21073909
TI  - Paclitaxel-loaded nanoparticles by temperature-induced phase transition.

PMID- 21073910
TI  - Parecoxib and its metabolite valdecoxib directly interact with cannabinoid
      binding sites in CB1-expressing HEK 293 cells and rat brain tissue.
AB  - Cyclooxygenase 2 inhibitors (COX 2) such as parecoxib (par) and valdecoxib (val)
      are used in the treatment of neuropathic pain. Using the radioligand binding
      assay it was demonstrated that both the prodrug par as well as its active
      metabolite val have a specific affinity to the cannabinoid (CB) receptor measured
      in CB1-expressing HEK 293 cells and rat brain tissue. Agonist activity was
      detected by GTPgammaS assays, cAMP formation experiments and ex vivo modulation
      of glutamate and GABA release of the rat brain tissue. In comparison to the
      specific cannabinoid agonist, WIN 55,212-2, the two COX 2 inhibitors are about 2
      orders of magnitude less potent. The data suggest that the analgesic effects of
      par and its metabolite val in Wistar rats may be at least partially mediated by a
      direct interaction with the CB1 receptors. The COX 2 inhibitors appear to be a
      hypothetically useful tool for add-on therapy of neuropathic pain.

PMID- 21073912
TI  - Anorexia nervosa and diabetes insipidus in pregnancy.

PMID- 21073911
TI  - Secalonic acid A reduced colchicine cytotoxicity through suppression of JNK, p38
      MAPKs and calcium influx.
AB  - There are few articles about the cytotoxicity evoked by secalonic acid A (SAA) in
      some tumor cells. It has not yet been reported whether SAA has any action on
      neurons of the central nervous system. The aim of this study was to investigate
      the protective effect of SAA against apoptosis of rat cortical neurons induced by
      colchicine. The protective action of SAA on the cortical neurons treated with
      colchicine at 1 MUM was examined by Hoechst 33258, LDH release and flow cytometry
      methods. The results from the above tests indicated that SAA at 3 and 10 MUM
      significantly prevented colchicine-induced apoptosis of the cortical neurons.
      Further studies from Western blot and confocal microscopy experiments showed that
      the activation of JNK, p38 MAPKs and caspase-3 during neuron apoptosis triggered
      by 1 MUM colchicine could be obviously suppressed by SAA; on the other hand, an
      increase in the intracellular free Ca(2+) by 1 MUM colchicine in the cortical
      neuron was blocked evidently by SAA. The above results suggested that SAA could
      antagonize the cytotoxicity of colchicine in the rat cortical neurons, which may
      be through inhibition of phosphorylation of JNK and p38 MAPKs, calcium influx,
      and the activation of caspase-3.

PMID- 21073913
TI  - Acute respiratory and systemic toxicity of pulmonary exposure to rutile Fe-doped
      TiO(2) nanorods.
AB  - Nanomaterials are extensively used in medicines, industry and daily life, but
      little is known about their possible health effects. Titanium dioxide (TiO2)
      nonmaterial-based photocatalysis is useful in the complete mineralization of
      organic pollutants in waste water and air. While the Fe-doping of TiO2 enhances
      their photocatalytic activity, their potential pathophysiologic effects are
      unknown. Here, rutile Fe-doped (9%) pure titanium dioxide (TiO2) nanorods were
      prepared and characterized. Subsequently, we assessed the acute (24 h) pulmonary
      and extrapulmonary effects of intratracheal (i.t.) instillation of these nanorods
      (1 and 5 mg/kg) in Wistar rats. In the bronchoalveolar lavage, the treatment
      induced a significant and dose-dependent increase of neutrophils, an increase of
      interleukin-6 (IL-6, at 5 mg/kg), and caused a dose-dependent-decrease of
      superoxide dismutase (SOD) activity. The lung sections of rats exposed to rutile
      Fe-TiO2 nanorods showed infiltration of inflammatory cells in dose-dependent
      manner. Similarly, the heart rate, systolic blood pressure, plasma IL-6, and
      leukocyte and platelet numbers were increased at 5 mg/kg. The plasma SOD and
      reduced glutathaione activities were dose-dependently decreased after exposure to
      the nanorods. Histopathologically, the liver showed mild inflammatory cells
      infiltration of few portal tracts, but the kidneys and heart were unaffected. In
      plasma, the levels of lactate dehydrogenase and hepatic enzymes, i.e., alanine
      aminotranferease and aspartate aminotransferase were increased significantly. The
      in vitro exposure of human lung cancer cells NCI-H460-Luc2 and human hepatoma
      cells HepG2 to FeTiO2 (6.25-100 MUg/ml) dose-dependently reduced cellular
      viability. Also, the In vitro direct addition of these nanorods (0.1-1 MUg/ml) to
      untreated rat blood, significantly and dose-dependently induced platelet
      aggregation. In conclusion, exposure to rutile Fe-TiO2 promotes pulmonary and
      systemic inflammation and oxidative stress. It affects the liver, enhances
      thrombotic potential, heart rate and systolic blood pressure. Moreover, the
      rutile Fe-TiO2 elicited direct toxicity on NCI-H460-Luc2 and HepG2 cells.

PMID- 21073914
TI  - E-photosynthesis: web-based platform for modeling of complex photosynthetic
      processes.
AB  - E-photosynthesis framework is a web-based platform for modeling and analysis of
      photosynthetic processes. Compared to its earlier version, the present platform
      employs advanced software methods and technologies to support an effective
      implementation of vastly diverse kinetic models of photosynthesis. We report on
      the first phase implementation of the tool new version and demonstrate the
      functionalities of model visualization, presentation of model components, rate
      constants, initial conditions and of model annotation. The demonstration also
      includes export of a model to the Systems Biology Markup Language format and
      remote numerical simulation of the model.

PMID- 21073915
TI  - Steroid sulfatase and estrogen sulfotransferase in human carcinomas.
AB  - Estrogens are closely involved in the development of hormone-dependent
      carcinomas. Estrone is locally produced from circulating inactive estrone sulfate
      by steroid sulfatase (STS), while estrone is inversely inactivated into estrone
      sulfate by estrogen sulfotransferase (EST). Recent studies suggested importance
      of this STS pathway in various human carcinomas. Therefore, in this review, we
      summarized recent results of STS and EST in several estrogen-dependent
      carcinomas. STS and EST expressions were detected in the breast and endometrial
      carcinomas, and activation of STS pathway due to increment in STS and/or
      decrement in EST expressions plays important role in their estrogen-dependent
      growth. STS expression was also reported in the ovarian and prostate carcinomas.
      STS/EST status was associated with intratumoral estrogen level in the colon
      carcinoma, and STS-negative/EST-positive colon carcinoma patients had longer
      survival. Therefore, STS pathway and estrogen actions may play an important role
      in the development of these carcinomas, and further investigations are required.

PMID- 21073916
TI  - Testing perceptual limits of functional units: Are there "automatic" tendencies
      to associate tools and objects?
AB  - Prior work has demonstrated a unique network involving the insula, temporal
      cortex, and precuneus in evaluating appropriate relationships between tool-object
      pairings under instruction [20]. However, are there automatic tendencies to
      evaluate appropriate tool-object pairings? Using electroencephalography (EEG), we
      emulated our prior work to identify neural mechanisms that, in the absence of
      task-related consciousness, differentiate functionally matching from mismatching
      tool-object pairs. This was compared to any activation consistent with this using
      environmental image pairs. In addition, based on the paradigm we were able to
      discern any naive processes that distinguish tools from non-tool environmental
      images. Results show that without task-related consciousness, the left
      occipitotemporal gyrus is preferentially active for tools compared to
      environmental images. Tool-object match and mismatch each versus control images
      show differences relative to a control image over the left temporal cortex,
      extending into the insula, yet there was no difference between tool-object match
      and mismatch. This suggests that there is no clear neural mechanism for continual
      evaluation of tool matching from mismatching, though there is for broad picture
      classifications. Taken together with our previous results, this creates a
      discussion for the role of intention when determining such relationships.

PMID- 21073917
TI  - Dynamic task-specific brain network connectivity in children with severe reading
      difficulties.
AB  - We investigated patterns of sensor-level functional connectivity derived from
      single-trial whole-head magnetoencephalography data during a pseudoword reading
      and a letter-sound naming task in children with reading difficulties (RD) and
      children with no reading impairments (NI). The Phase Lag Index (PLI), a linear
      and nonlinear estimator, computed for each pair of sensors, was used to construct
      graphs and obtain estimates of local and global network efficiency according to
      graph theory. In the 8-13 Hz (alpha band) and 20-30 Hz (gamma band) range, RD
      students showed significantly lower global efficiency than NI children, for the
      entire MEG recording epoch. RD students also displayed reduced local network
      efficiency in the alpha band. Correlations between phonological decoding ability
      and graph metrics were particularly evident during the task that posed
      significant demands for phonological decoding, and followed distinct time courses
      depending on signal frequency. Results are consistent with the notion of task
      dependent, aberrant long- and short-range functional connectivity in RD children.

PMID- 21073918
TI  - c-Jun N terminal kinases (JNK) are activated in the brain during the pathology of
      experimental cerebral malaria.
AB  - Experimental cerebral malaria (ECM) resulting from Plasmodium berghei ANKA (PbA)
      infection in C57BL/6J mice manifests cell death in the brain. However, the
      precise molecular and biochemical mechanisms regulating cell death during ECM
      remains unknown. In this study we have examined, the role of a stress activated
      protein kinase called c-Jun N terminal kinase during the pathology of ECM. We
      report in this study, for the first time the activation of all key elements in
      the JNK pathway like p-MKK4, p-JNK and p-c-Jun in mouse brain during ECM.
      Concomitant with such activation was the up regulation of p-JNK and its
      translocation into the nucleus leading to the phosphorylation of its major
      substrate c-Jun. These observations show the neuronal induction of p-JNK and its
      critical role as a mediator in neuronal cell death during ECM.

PMID- 21073920
TI  - Short-term effects on postural control can be evidenced using a seesaw.
AB  - Postural control strategies are frequently assessed through posturography on a
      firm surface. Their motor efficiency is related to the coordination between
      center-of-gravity (CG) and center-of-pressure (CP) movements, which results from
      long-term training. However, when standing on a seesaw favoring pitching body
      motions, a new coordination, requiring short-term training, needs to be learned
      again. On this type of device, somesthetic cues from the ankle joints become
      invalid and motor command is amplified because of the curvature of the contact
      ridges. To highlight the mechanisms involved in short-term improvements of
      postural control, 11 healthy young adults were trained for 20 min by standing on
      a seesaw with their eyes closed. Two series of posturographic measurements,
      before and after the training, were recorded whilst the subjects stood on the
      seesaw with eyes closed. The results indicate a reduction in the horizontal CG
      displacements along the anteroposterior axis and CP-CG displacements along both
      anteroposterior and mediolateral axes. Fractional Brownian motion (fBm) analysis
      further explains these lessened CG movements by highlighting a reduced distance
      covered before the corrective mechanisms take over. The other fBm parameters, the
      contribution of stochastic activity during the shortest and longest time
      intervals or the time interval of the transition points (which expresses the mean
      delay before the corrective mechanisms take over), remained unchanged. These
      results could likely be explained by reduced tonic muscular activity of the lower
      limbs and/or recalibration of the sensory systems in order to improve the
      detection of the CG movements.

PMID- 21073919
TI  - Unilateral infarction of the visual cortex (VC) induced an increase in dendritic
      spine turnover in contralateral VC.
AB  - After brain stroke, appropriate functional recovery is most important for
      improvement of quality of life. Cortical hemisphere contralateral to the
      infarction site plays an important role in functional recovery process. However,
      the underlying processes occurring in contralateral hemisphere during recovery
      has not yet been elucidated. We have previously reported that the turnover of
      synaptic spine of somatosensory cortex (SSC) is increased at 1st week after
      stroke in contralateral SSC infarction. After this period, neuronal circuit is
      remodeled, and functional compensation is achieved by processing bilateral
      information to remaining SSC [18]. In the present study, to examine whether
      similar changes are observed in different brain regions, we have induced an
      infarction in the visual cortex (VC). We found that the spinal remodeling in
      contralateral VC was also increased at 1st week after VC stroke. However, the
      magnitude of changes was not as great as those seen in SSC infraction. These
      results indicate that the regional difference may exist in the ability to induce
      functional recovery after ischemic brain damage.

PMID- 21073921
TI  - Sympathoinhibition to Bezold-Jarisch reflex is attenuated in protein malnourished
      rats.
AB  - Malnutrition affects cardiovascular reflexes, including chemoreflex and
      baroreflex. In this study we assessed the hypothesis that malnourishment changes
      the responses in mean arterial pressure (MAP), heart rate (HR) and renal
      sympathetic nerve activity (RSNA) evoked from Bezold-Jarisch reflex (BJR).
      Fischer rats were fed diets containing either (6% malnourished or 14% control)
      protein for 35 days after weaning. There were no differences in baseline MAP (102
      +/- 4 vs. 95 +/- 3 mmHg) whereas higher baseline HR (478 +/- 18 vs. 360 +/- 11
      bpm; P<0.05,) and reduced sympathoinhibition (DeltaRSNA=-54 +/- 9 vs. -84 +/- 7%;
      P=0.0208) to BJR activation were found in malnourished rats. We conclude that
      malnutrition affects the sympathetic control of BJR.

PMID- 21073922
TI  - The participation of a neurocircuit from the paraventricular thalamus to amygdala
      in the depressive like behavior.
AB  - Depression is a neuropsychological disease derived from genetic, biochemical,
      environmental, and psychological factors. However the neurocircuits involved in
      it are not clear. We introduced the forced swimming test (FST) as a model of the
      depressive like behavior. In our study, the participation of projections from
      paraventricular nucleus of the thalamus (PVT) in FST was detected. The retrograde
      tracing combined with immunofluorescent detection of c-fos was used. Our results
      showed that the FST greatly increased the c-fos level in PVT and the central
      amygdale (CE) neurons. These populations of activated neurons in the PVT and the
      CE were also labeled by the retrograde tracer FG injected in the CE, suggesting
      that the activation of PVT was involved in this depressive like behavior by
      relaying information to the CE.

PMID- 21073923
TI  - Consonant chords stimulate higher EEG gamma activity than dissonant chords.
AB  - We examined the perceptions of consonant and dissonant chords to test auditory
      coherent percepts that are related to gamma oscillation. Consonant chords have
      coherent auditory properties due to the physical relationships of their
      components, in contrast to dissonant chords. EEGs were measured on 18 subjects
      with no musical expertise while they listened to consonant chords, dissonant
      chords, and single-note sounds and counted the number of single tones they heard.
      Induced gamma band activity was observed over the right brain hemisphere 170ms
      after the onset of stimuli. The induced gamma activity was significantly
      increased while listening to consonant chords as compared to dissonant chords.
      Our results suggest that the neural activity of the gamma frequency bands may
      reflect an auditory coherent percept generated from physical relationships of
      sounds.

PMID- 21073924
TI  - SUN N8075, a novel radical scavenger, protects against retinal cell death in
      mice.
AB  - In this study, we examined the effect of SUN N8075, a radical scavenger with
      neuroprotective properties, on murine retinal damage induced by intravitreous
      injection of N-methyl-d-aspartate (NMDA) or high-intraocular pressure (IOP). In
      both models, systemic administration of SUN N8075 decreased the cell loss in the
      ganglion cell layer (GCL) after retinal damage occurred. Moreover, SUN N8075
      reduced the number of apoptotic cells and the expression of an oxidative stress
      marker in GCL in the NMDA model. These findings suggest that SUN N8075 has a
      neuroprotective effect against retinal damage, presumably via the radical
      scavenging effect.

PMID- 21073926
TI  - Neuroprotective effects of NAP against excitotoxic brain damage in the newborn
      mice: implications for cerebral palsy.
AB  - Activity-dependent neuroprotective protein (ADNP) was shown to be essential for
      embryogenesis and brain development while NAP, an active motif of ADNP, is
      neuroprotective in a broad range of neurodegenerative disorders. In the present
      study, we examined the protective potential of ADNP/NAP in a mouse model of
      excitotoxic brain lesion mimicking brain damage associated with cerebral palsy.
      We demonstrated that NAP had a potent neuroprotective effect against ibotenate
      induced excitotoxic damage in the cortical plate and the white matter of P5 mice,
      and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP
      appears not to be involved in the response to excitotoxic challenge in the
      studied model. Our findings further show that NAP reduced the number of apoptotic
      neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI
      3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented
      ibotenate-induced loss of pre-oligodendrocytes without affecting the number of
      astrocytes or activated microglia around the site of injection. These findings
      indicate that protective actions of NAP are mediated by triggering transduction
      pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP
      might be a promising therapeutic agent for treating developing brain damage.

PMID- 21073925
TI  - Long-term memory of visually cued fear conditioning: roles of the neuronal nitric
      oxide synthase gene and cyclic AMP response element-binding protein.
AB  - Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in
      late-phase long-term potentiation (LTP) and long-term memory (LTM) formation. Our
      recent studies implicated NO signaling in contextual and auditory cued fear
      conditioning. The present study investigated the role of NO signaling in visually
      cued fear conditioning. First, visually cued fear conditioning was investigated
      in wild-type (WT) and nNOS knockout (KO) mice. Second, the effects of
      pharmacological modulators of NO signaling on the acquisition of visually cued
      fear conditioning were investigated. Third, plasma levels of corticosterone were
      measured to determine a relationship between physiological and behavioral
      responses to fear conditioning. Fourth, levels of extracellular signal-related
      kinase (ERK1/2) and cyclic AMP response element binding protein (CREB)
      phosphorylation, downstream of NO signaling, were determined in the amygdala as
      potential correlates of fear learning. Mice underwent single or multiple (4)
      spaced trainings that consisted of a visual cue (blinking light) paired with
      footshock. WT mice acquired cued and contextual LTM following single and multiple
      trainings. nNOS KO mice acquired neither cued nor contextual LTM following a
      single training; however, multiple trainings improved contextual but not cued
      LTM. The selective nNOS inhibitor S-methyl-thiocitrulline (SMTC) impaired cued
      and contextual LTM in WT mice. The NO donor molsidomine recovered contextual LTM
      but had no effect on cued LTM in nNOS KO mice. Re-exposure to the visual cue 24 h
      posttraining elicited freezing response and a marked increase in plasma
      corticosterone levels in WT but not nNOS KO mice. The expression of CREB
      phosphorylation (Ser-133) was significantly higher in naive nNOS KO mice than in
      WT counterparts, and pharmacological modulators of NO had significant effects on
      levels of CREB phosphorylation and expression. These findings suggest that visual
      cue-dependent LTM is impaired in nNOS KO mice, and aberrant modulation of CREB in
      the absence of the nNOS gene may hinder cued and contextual LTM formation.

PMID- 21073927
TI  - Sleep deprivation impairs spatial learning and modifies the hippocampal theta
      rhythm in rats.
AB  - Previous work from our laboratory suggests that paradoxical sleep deprivation
      (PSD) decreases persistent sodium currents and hyperpolarization-activated cation
      currents in CA1 pyramidal neurons, and this leads to decreases in neuron
      excitability. Here, we further investigate the mechanisms of rhythmic theta-range
      activity in the hippocampus by examining the resonance characteristics of
      hippocampal pyramidal neurons. Sleep deprivation (SD) interfered with the
      rhythmic activity of theta band in the hippocampus, which may be involved in the
      deficit of the spatial learning ability of rats. Additionally, SD changes the
      voltage dependence of resonance. The effect of SD on the ion currents may
      contribute to the alternation of the theta resonance of neurons and further
      influence the physiological function. These results suggest that changes in
      neuron resonance lead to changes in the generation of rhythmic theta activity,
      and may contribute to behavioral deficits associated with theta activity during
      learning and memory tasks. We suggest the resonant properties of hippocampal
      neurons are potential targets for preventing deleterious effects of sleep
      deprivation.

PMID- 21073928
TI  - Modification of activation kinetics of delayed rectifier K+ currents and neuronal
      excitability by methyl-beta-cyclodextrin.
AB  - The effects of methyl-beta-cyclodextrin (MbetaCD), an oligosaccharide, on ion
      currents were investigated in differentiated NG108-15 neuronal cells. In NG108-15
      cells treated with dibutyryl cyclic AMP, the expression level of the K(V)3.1 mRNA
      was elevated. Depletion of membrane cholesterol by exposing cells to MbetaCD (1
      mM) resulted in a significant reduction of the activation kinetics of delayed
      rectifier K(+) current (I(K)((DR))) in these cells. However, neither activation
      nor inactivation curve of I(K(DR)) was altered following MbetaCD treatment. In
      current-clamp recordings, in MbetaCD-treated cells, the instantaneous frequency
      of the firing in response to long-lasting current stimuli was reduced. In a
      modified Hodgkin-Huxley neuron, the upward shift in the relationship of
      activation/deactivation time constant of I(K(DR)) versus membrane potential
      causes a reduction of I(K(DR)) amplitude accompanied by an increase in the width
      of action potentials. In the studies from a high-frequency modeled neuron,
      reduction of voltage-dependent activation of I(K(DR)) can also facilitate spike
      frequency adaptation. In a simulated network of spiking neurons, the increased
      activation/deactivation time constant of I(K(DR)) slowed repetitive firing. Taken
      together, MbetaCD may slow activation kinetics of I(K(DR)) and confer a trigger
      for the propensity to develop spike-frequency adaptation in neurons or
      neuroendocrine cells.

PMID- 21073929
TI  - Visual context modulates the subjective vertical in neglect: evidence for an
      increased rod-and-frame-effect.
AB  - Patients with spatial hemi-neglect display systematic deviations of the
      subjective vertical. The magnitude of such deviations was shown to be modulated
      by internal factors mediating the perception of verticality, including head
      orientation. The present study investigated whether and how spatial orientation
      deficits are modulated by external, contextual changes in neglect patients. In a
      classic rod-and-frame task, we analyzed effects of frame orientation on the
      subjective visual vertical (SVV) in neglect patients, control patients with left-
      or right-sided brain damage without neglect and healthy participants. We found
      that neglect patients, but not brain-damaged control patients, generally display
      a systematic counterclockwise (CCW) tilt in their SVV judgments. Furthermore, all
      participant groups displayed a typical rod-and-frame effect (RFE), that is, a
      modulation of the SVV as a function of frame tilt. However, in the control
      groups, this modulation was only moderate whereas in the neglect group SVV
      judgments were substantially and systematically modulated by frame orientation:
      with CCW frame tilts, the spatial bias of neglect patients increased as a
      function of the magnitude of the tilt whereas with clockwise (CW) frame tilts,
      the spatial bias was decreased in case of moderate frame tilts and even reversed
      in case of stronger frame tilts, resulting in a substantial CW spatial bias. This
      dramatically enhanced RFE might be caused by a pathologically increased influence
      of contextual cues on the subjective vertical in neglect patients as a
      consequence of impaired processing of gravitational information. The results
      indicate a systematic bias of the subjective vertical along with an impairment of
      spatial orientation constancy which leads to severe perturbations of subjective
      space as well as an increased reliance on internal and external cues mediating
      the perception of verticality in neglect.

PMID- 21073930
TI  - Regulation of research: is it a drug trial or a supplement trial?
AB  - Investigators and sponsors of dietary supplement research need to know the
      relevant regulatory requirements and how to comply with them. This brief review
      describes how research on dietary supplements is regulated by FDA. In general,
      whether an FDA sanctioned Investigational New Drug (IND) application is required
      for a human research project on dietary supplement depends on the intended use
      and clinical setting of the clinical study, and not on the supplement's physical
      or chemical properties. Even if the study product is already available on the
      market as a dietary supplement, an IND will be required for products that will be
      used as a drug to treat, mitigate or prevent a disease or its related conditions
      in the proposed clinical study. On the other hand, for studies on structure and
      function endpoints, and not on drug use, no IND will be required. The paper also
      discusses the principles FDA uses to determine whether an IND is needed for
      clinical studies of surrogate endpoints that do not lead to approvable drug
      claims. Useful FDA contact information is also provided.

PMID- 21073931
TI  - Tithonia diversifolia and its main active component tagitinin C induce survivin
      inhibition and G2/M arrest in human malignant glioblastoma cells.
AB  - We investigated the antitumour activity of Tithonia diversifolia (TD) on
      malignant glioblastoma cells. Our results suggested that tagitinin C was the main
      component in viability inhibition on malignant glioblastoma cells, and also
      accounted to be the most abundant component (>65%) in TD extract. Both TD extract
      and tagitinin C exhibited vigorous potential to produce in vitro viability
      inhibition, autophagic cell death and G2/M arrest. Furthermore, the activity of
      survivin, a critical resistant-factor in cancer therapy, could be downregulated
      significantly by TD extract and tagitinin C. These findings suggested that TD
      extract and tagitinin C were effective for treating malignant glioblastoma.

PMID- 21073932
TI  - Berberine attenuates lipopolysaccharide-induced impairments of intestinal
      glutamine transport and glutaminase activity in rat.
AB  - Berberine was reported to protect against the intestinal injury and improve the
      survival rate in sepsis, and glutamine deficiency was considered to be correlated
      with mortality in sepsis. We found that berberine pretreatment ameliorated
      lipopolysaccharide-induced direct intestinal injury and mucosal hypoplasia and
      attenuated impairments of intestinal glutamine transport and glutaminase
      activity, B(0)AT1 mRNA and protein expressions, and glutaminase protein
      expression. These findings showed the first time that berberine pretreatment
      could improve intestinal recovery and attenuate the impairment of glutamine
      transport and glutaminase activity in rat sepsis. This might be one of the
      mechanisms for the beneficial effect of berberine on sepsis.

PMID- 21073933
TI  - Auditory cortex tracks the temporal regularity of sustained noisy sounds.
AB  - Neuroimaging studies have revealed dramatic asymmetries between the responses to
      temporally regular and irregular sounds in the antero-lateral part of Heschl's
      gyrus. For example, the magnetoencephalography (MEG) study of Krumbholz et al.
      [Cereb. Cortex 13, 765-772 (2003)] showed that the transition from a noise to a
      similar noise with sufficient temporal regularity to provoke a pitch evoked a
      pronounced temporal-regularity onset response (TRon response), whereas a
      comparable transition in the reverse direction revealed essentially no temporal
      regularity offset response (TRoff response). The current paper presents a follow
      up study in which the asymmetry is examined with much greater power, and the
      results suggest an intriguing reinterpretation of the onset/offset asymmetry. The
      TR-related activity in auditory cortex appears to be composed of a transient
      (TRon) and a TR-related sustained response (TRsus), with a highly variable
      TRon/TRsus amplitude ratio. The TRoff response is generally dominated by the
      break-down of the TRsus activity, which occurs so rapidly as to preclude the
      involvement of higher-level cortical processing. The time course of the TR
      related activity suggests that TR processing might be involved in monitoring the
      environment and alerting the brain to the onset and offset of behaviourally
      relevant, animate sources.

PMID- 21073934
TI  - Hearing and vestibular deficits in the Coch(-/-) null mouse model: comparison to
      the Coch(G88E/G88E) mouse and to DFNA9 hearing and balance disorder.
AB  - Two mouse models, the Coch(G88E/G88E) or "knock-in" and the Coch(-/-) or "knock
      out" (Coch null), have been developed to study the human late-onset, progressive,
      sensorineural hearing loss and vestibular dysfunction known as DFNA9. This
      disorder results from missense and in-frame deletion mutations in COCH
      (coagulation factor C homology), encoding cochlin, the most abundantly detected
      protein in the inner ear. We have performed hearing and vestibular analyses by
      auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing
      of the Coch(-/-) and Coch(G88E/G88E) mouse models. Both Coch(-/-) and
      Coch(G88E/G88E) mice show substantially elevated ABRs at 21 months of age, but
      only at the highest frequency tested for the former and all frequencies for the
      latter. At 21 months, 9 of 11 Coch(-/-) mice and 4 of 8 Coch(G88E/G88E) mice have
      absent ABRs. Interestingly Coch(-/+) mice do not show hearing deficits, in
      contrast to Coch(G88E/+), which demonstrate elevated ABR thresholds similar to
      homozyotes. These results corroborate the DFNA9 autosomal dominant mode of
      inheritance, in addition to the observation that haploinsufficiency of Coch does
      not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds
      were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds
      are detected in Coch(-/-) mice at 13 and 21 months, the two ages tested, and as
      early as seven months in the Coch(G88E/G88E) mice. These results indicate that in
      both mouse models, vestibular function is compromised before cochlear function.
      Analysis and comparison of hearing and vestibular function in these two DFNA9
      mouse models, where deficits occur at such an advanced age, provide insight into
      the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as
      well as an opportunity to investigate potential interventional therapies.

PMID- 21073935
TI  - The effects of experimentally induced conductive hearing loss on spectral and
      temporal aspects of sound transmission through the ear.
AB  - Conductive hearing loss (CHL) is known to produce hearing deficits, including
      deficits in sound localization ability. The differences in sound intensities and
      timing experienced between the two tympanic membranes are important cues to sound
      localization (ILD and ITD, respectively). Although much is known about the effect
      of CHL on hearing levels, little investigation has been conducted into the actual
      impact of CHL on sound location cues. This study investigated effects of CHL
      induced by earplugs on cochlear microphonic (CM) amplitude and timing and their
      corresponding effect on the ILD and ITD location cues. Acoustic and CM
      measurements were made in 5 chinchillas before and after earplug insertion, and
      again after earplug removal using pure tones (500 Hz to 24 kHz). ILDs in the
      unoccluded condition demonstrated position and frequency dependence where peak
      far-lateral ILDs approached 30 dB for high frequencies. Unoccluded ear ITD cues
      demonstrated positional and frequency dependence with increased ITD cue for both
      decreasing frequency (+/-420 MUs at 500 Hz, +/-310 MUs for 1-4 kHz) and
      increasingly lateral sound source locations. Occlusion of the ear canal with foam
      plugs resulted in a mild, frequency-dependent conductive hearing loss of 10-38 dB
      (mean 31 +/- 3.9 dB) leading to a concomitant frequency dependent increase in
      ILDs at all source locations. The effective ITDs increased in a frequency
      dependent manner with ear occlusion as a direct result of the acoustic properties
      of the plugging material, the latter confirmed via acoustical measurements using
      a model ear canal with varying volumes of acoustic foam. Upon ear plugging with
      acoustic foam, a mild CHL is induced. Furthermore, the CHL induced by acoustic
      foam results in substantial changes in the magnitudes of both the ITD and ILD
      cues to sound location.

PMID- 21073936
TI  - Houttuynia cordata, a novel and selective COX-2 inhibitor with anti-inflammatory
      activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (Saururaceae; HC) has
      been long used in traditional oriental medicine for the treatment of inflammation
      diseases. Modern research has implicated inducible cyclooxygenase-2 (COX-2) as a
      key regulator of the inflammatory process. AIM OF THE STUDY: In the present
      study, we aimed to investigate the effect of HC on COX-2. We examined the effects
      of HC on lipopolysaccharide (LPS)-induced prostaglandin (PG) E(2) production, an
      indirect indicator of COX-2 activity, and COX-2 gene and protein expression in
      mouse peritoneal macrophages. MATERIALS AND METHODS: LPS-induced mouse peritoneal
      macrophages were employed as an in vitro model system. LPS-induced PGE(2)
      production was assessed by enzyme-linked immunosorbant assay and COX-2 protein
      expression was assessed by Western blot assay. RESULTS: The results showed that
      HC was able to inhibit the release of LPS-induced PGE(2) from mouse peritoneal
      macrophages (IC50 value: 44.8 MUg/mL). Moreover, the inhibitory activity of HC
      essential oil elicited a dose-dependent inhibition of COX-2 enzyme activity (IC50
      value: 30.9 MUg/mL). HC was also found to cause reduction in LPS-induced COX-2
      mRNA and protein expression, but did not affect COX-1 expression. The non
      steroidal anti-inflammatory drug (NSAID) and specific COX-2 inhibitor NS398
      functioned similarly in LPS-induced mouse peritoneal macrophages. CONCLUSION:
      Taken together, our data suggest HC mediates inhibition of COX-2 enzyme activity
      and can affect related gene and protein expression. HC works by a mechanism of
      action similar to that of NSAIDs. These results add a novel aspect to the
      biological profile of HC.

PMID- 21073937
TI  - Comparison of the chemical profiles and anti-platelet aggregation effects of two
      "Dragon's Blood" drugs used in traditional Chinese medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: "Dragon's Blood" has been used as a medicine
      since ancient times by many cultures. In traditional Chinese medicine, the resin
      obtained from Daemonorops draco (RDD) and the resin from Dracaena cochinchinensis
      (RDC) are equally prescribed as "Dragon's Blood" for facilitating blood
      circulation. AIM OF THE STUDY: To verify the traditional efficacy and elucidate
      the mechanism, the present study compared the chemical profiles and the
      pharmacological effects of two species of "Dragon's Blood" mainly used in China.
      MATERIALS AND METHODS: A UPLC-MS fingerprinting method was developed to compare
      the chemical profiles of the two medicines. The anti-platelet aggregation effects
      of the two medicines induced by arachidonic acid (AA) were investigated. RESULTS:
      The chemical profiles of these two species of "Dragon's Blood" were significantly
      different. The characteristic constituents were found to be: flavanes in RDD and
      stilbenes in RDC. In the in vivo platelet inhibition test, performed with the
      dose of 200 mg/kg on rats, the peak inhibitory effects of RDD and RDC were 35.8%
      and 27.6%, respectively, compared with the control group. With the in vitro
      concentrations of 0.2, 0.4 and 0.8 mg/ml, RDD exerted significant inhibition of
      aggregation by 18.7%, 20.0%, and 61.6%, respectively, and RDC exerted significant
      inhibition of aggregation by 13.3%, 20.2%, and 31.6%, respectively. CONCLUSION:
      The fingerprinting method used here is suitable for distinguishing them. All
      pharmacological tests indicated that RDD was more potent than RDC against
      platelet aggregation.

PMID- 21073938
TI  - A strategy for detecting optimal ratio of cardioprotection-dependent three
      compounds as quality control of guan-xin-er-hao formula.
AB  - AIMS: We aimed to detect optimal ratio of cardioprotection-dependent absorbed
      bioactive compounds (ABCs) as quality control of guan-xin-er-hao (GXEH) formula
      extracted by various processings. METHODS: Ferulic acid (F), tanshinol (T),
      hydroxysafflor yellow A (A), protocatechualdehyde (P) and paeoniflorin (E) in
      GXEH formula and FTA in blood from rat with acute myocardial infarction (AMI)
      were first identified by HPLC-MS/MS, and FTAPE in GXEH formulae with various
      herbs, extraction times and extraction water volumes were then quantitated only
      by HPLC. RESULTS: FTAPE in various GXEH were determined. FTA were selected as
      GXEH's ABCs. Ratios of FTA were determined, suggesting the high (1:6.1:15.6),
      medium (1:1.7:15.2) and low (1:0.2:15.3) ratios. Three FTA ratios and their
      parent formulae ratio-dependently reduced infarct size, myocardial apoptosis and
      caspase-3 activity. CONCLUSION: There is the optimal ratio of F:T:A among various
      formulae, contributing to the best cardioprotection. This FTA ratio was developed
      as quality control of GXEH formula.

PMID- 21073939
TI  - Effects of Juniperus oxycedrus ssp. oxycedrus on tissue lipid peroxidation, trace
      elements (Cu, Zn, Fe) and blood glucose levels in experimental diabetes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Juniperus oxycedrus L. (Cupressaceae) fruits and
      leaves are used internally and pounded fruits are eaten for diabetes in Turkey.
      AIM OF THE STUDY: To evaluate the interrelationships between the levels of chosen
      trace elements (copper, iron, and zinc) and hepatic, renal lipid peroxidation
      (TBARS) in streptozotocin-induced diabetic rats treated with Juniperus oxycedrus
      ssp. oxycedrus (J.o.s.o.) leaf and fruit extracts for 10 days. MATERIALS AND
      METHODS: J.o.s.o. fruit and leaf extracts were administered in STZ-induced
      diabetic rats, at doses of 500 and 1000 mg/kg. The blood glucose levels were
      measured in the 1st, 4th, 7th and 10th day of experiment. Fe, Cu, and Zn contents
      and lipid peroxidation levels of liver and kidney tissues were determined by
      atomic absorption spectrophotometry and ultraviolet spectrophotometry,
      respectively. RESULTS: Treatment of diabetic rats with the J.o.s.o. fruit and
      leaf extracts decreased the blood glucose levels and both the levels of lipid
      peroxidation in liver and kidney tissues. J.o.s.o. extracts have augmented Zn
      concentrations in liver of STZ-induced diabetic rats. CONCLUSIONS: Results
      indicated that J.o.s.o. fruit and leaf extracts might be beneficial for diabetes
      and its complications.

PMID- 21073940
TI  - Antioxidant and anti-inflammatory properties of Cardiospermum halicacabum and its
      reference compounds ex vivo and in vivo.
AB  - AIMS OF THE STUDY: Cardiospermum halicacabum (CH) has been used in Chinese
      medicine for a long time. However, its fingerprint chromatogram, antioxidant,
      anti-inflammatory effects and mechanism are still needed to be explored.
      Therefore, the aims of this study investigated the antioxidant and anti
      inflammatory effects of CH extracts and its reference compounds ex vivo and in
      vivo. MATERIALS AND METHODS: In HPLC analysis, the fingerprint chromatogram of
      ethanolic extract of CH (ECH) was established. The effects of ACH (aqueous
      extract of CH) and ECH extracts were assessed for the antioxidant and LPS-induced
      NO production in RAW264.7 cells. In vivo anti-inflammatory activities of ECH were
      evaluated in mouse paw edema induced by lambda-carrageenan (Carr). We investigate
      the anti-inflammatory mechanism of ECH via studies of the activities of catalase
      (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver
      and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the edema paw.
      Serum NO and TNF-alpha were also measured. RESULTS: ECH had better antioxidant
      activity than that of ACH. In the anti-inflammatory test, ECH inhibited the
      development of paw edema induced by Carr and increased the activities of CAT, SOD
      and GPx in the liver tissue. ECH also decreased the level of NO in edematous paw
      tissue and in serum level, and diminished the level of serum TNF-alpha at the
      fifth hour after Carr injection. CONCLUSIONS: ECH exerts anti-inflammatory
      effects by suppressing TNF-alpha and NO. The anti-inflammatory mechanism of ECH
      might be related to the decrement of the level of MDA in the edema paw via
      increasing the activities of CAT, SOD and GPx in the liver. The results showed
      that ECH might serve as a natural antioxidant and anti-inflammatory agent.

PMID- 21073941
TI  - Spatholobus suberectus inhibits cancer cell growth by inducing apoptosis and
      arresting cell cycle at G2/M checkpoint.
AB  - AIM OF THE STUDY: Although herbs have long been alternatively applied for cancer
      treatment in China, its treatment effects and their potential mechanisms have not
      been sufficiently investigated. The chinese herb Spatholobus suberectus (SS) is
      commonly prescribed to cancer patients. In this study, the anti-cancer effect of
      SS and its molecular mechanisms have been investigated. MATERIALS AND METHODS:
      The effect of SS on cell proliferation was studied by cell growth assay and flow
      cytometry on breast cancer cell lines MCF-7 and colon cancer cell line HT-29. The
      role of SS in apoptosis was studied by flow cytometry, DNA fragmentation assay
      and mitochondrial membrane potential assay. Expression of proteins associated
      with cell cycle and apoptosis was determined by Western blot analysis. The in
      vivo effect of SS was tested in nude mouse cancer xenografts. RESULTS: Cell
      growth assay showed that SS effectively inhibits tumor cell growth in a dose
      dependent manner. Flow cytometry analysis showed that SS could arrest the cell
      cycle at G2/M checkpoint, which is associated with DNA damage and activation of
      phosphor-Chk1/Chk2. The pro-apoptotic effect of SS was demonstrated by Annexin V
      PI staining and mitochondrial membrane potential assay. In vivo experiments show
      that the efficiency of SS alone group was superior to docetaxel or to docetaxel
      and SS combined. No obvious body weight loss or blood toxicity was observed in SS
      tested animals. CONCLUSIONS: Our data demonstrates that SS is a potential herb
      for cancer treatment by inhibiting tumor growth via induction of apoptosis and
      arrest of the cell cycle at G2/M phase.

PMID- 21073942
TI  - Ginseng total saponins enhance neurogenesis after focal cerebral ischemia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng, the root of Panax ginseng C.A. Meyer, is
      one of the most commonly used healing herbs for stroke and chronic debilitating
      conditions in China. Ginsenosides are the main active principles for ginseng's
      efficacy, but the mechanisms have not been fully clarified. AIM OF THE STUDY: To
      test the hypothesis whether or not the administration of Ginseng total saponins
      (GTS) can enhance neurogenesis after focal cerebral ischemia, and thereby improve
      neurological deficits. MATERIALS AND METHODS: Male Wistar rats received
      intraperitoneal injections of GTS dissolved at a dose of 25 mg kg(-1) d(-1) or
      normal saline (NS) of same volume 3 days before the permanent middle cerebral
      artery occlusion (MCAO) model establishment until the animals were killed at the
      time points of 1d, 3d, 7d and 14d. The neurological function was assessed
      blindly. BrdU immunostaining and double staining were performed by following the
      3-steps method. RESULTS: (A) GTS-treated rats have better neurological scores
      compared with those in NS group at 14d time point (p<0.05); (B) the number of
      BrdU(+) cells and BrdU(+)/NeuN(+) cells in GTS group were significantly higher
      than those in NS group in the ipsilateral subventricular zone and in the
      ipsilateral infarct area after MCAO, respectively (p<0.05 or p<0.01); (C) the
      increase of the number of BrdU(+)/NeuN(+) cells highly correlated with the
      decrease of neurological scores. Coefficient correlation r=-0.828 (p<0.01).
      CONCLUSION: GTS can improve neurological deficits after focal cerebral ischemia
      by inducing endogenous neural stem cells activation and thereby enhance adult
      central nervous system regeneration.

PMID- 21073943
TI  - Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition
      by suppressing cyclin D1 expression and matrix-metalloproteinase-2 activity in
      human lung cancer cells.
AB  - AIM OF THE STUDY: Scutellaria baicalensis Georgi is a widely used medicinal herb
      in several Asian countries including Korea. The various medicinal properties
      attributed to Scutellaria baicalensis include anti-bacterial, anti-viral, anti
      inflammatory and anti-cancer effects. The present study investigated the
      cytotoxicity of Scutellaria baicalensis water extract (SBWE) on A549 non-small
      cell-lung cancer cells and the A549 expression of cyclin D1, cyclin-dependent
      kinase 4 (CDK4) and matrix metalloproteinase-2 (MMP-2), and the effects of SBWE
      on cell cycle progression, especially the G1/S phase, and on cell motility.
      MATERIALS AND METHODS: SBWE cytotoxicity was assessed by a standard colorimetric
      assay utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) and expression of cyclin D1 and CDK4 protein in SBWE-treated A549 cells was
      assessed by Western blot analysis. Flow cytometry analysis was performed to
      determine the effect of SBWE on A549 cell cycle progression. A549 cell MMP-2
      activity was examined by zymography. Cell motility and migration was assessed by
      a scratch wound healing assay. RESULTS: SBWE was not cytotoxic. The production of
      Cyclin D1, CDK4 and MMP-2 activity were significantly decreased in a SBWE dose
      dependent manner, with maximum inhibition occurring at SBWE concentrations of 250
      MUg/ml and 500 MUg/ml. SBWE inhibited cell cycle progression in the G1/S phase
      and significantly inhibited the motility of A549 cells. CONCLUSIONS: Cyclin D1
      protein may be associated with MMP-2 activity and cell motility. Thus, SBWE
      promotes a strong protective effect against MMP-2 mediated metastasis and cell
      proliferation through the down-regulation of cyclin D1. SBWE may be a useful
      chemotherapeutic agent for lung cancer.

PMID- 21073944
TI  - Progallin A isolated from the acetic ether part of the leaves of Phyllanthus
      emblica L. induces apoptosis of human hepatocellular carcinoma BEL-7404 cells by
      up-regulation of Bax expression and down-regulation of Bcl-2 expression.
AB  - AIM OF THE STUDY: This study was aimed to investigate the effects of Progallin A
      isolated from the acetic ether part of the leaves of Phyllanthus emblica L. on
      apoptosis in human hepatocellular carcinoma BEL-7404 cells and its possible
      mechanisms, and to measure the immune toxicity of Progallin A in vitro. MATERIALS
      AND METHODS: Progallin A was isolated from the acetic ether part of the leaves of
      Phyllanthus emblica L. with column chromatography. The proliferation of spleen
      lymphocytes and the viability of BEL-7404 cells were assessed with MTT assay.
      Inverted microscope, light microscope and fluorescence microscope were utilized
      to observe the morphological changes of BEL-7404 cells respectively. AnnexinV/PI
      double labeling and TUNEL assay were used to detect early apoptosis and DNA
      fragmentations of BEL-7404 cells respectively. In addition, cell cycle
      distribution was analyzed by using flow cytometry (FCM). Bax and Bcl-2 protein
      levels were determined by immunofluorescence staining and western blot
      respectively. RESULTS: The results showed that Progallin A had low immune
      toxicity and the proliferation of BEL-7404 cells was strongly inhibited by
      Progallin A in a time- and dose-dependent manner and that the characteristics of
      apoptosis of BEL-7404 cells were observed. The results also showed that apoptosis
      rates and the number of apoptotic cells significantly increased with prolongation
      of the action time. The results of flow cytometry (FCM) indicated that Progallin
      A induced significant G1/M and G2/M arrest of BEL-7404 cells. Immunofluorescence
      staining and western blot showed that the expression of Bax was found to be
      noticeably up-regulated and the expression of Bcl-2 was down-regulated
      significantly. CONCLUSIONS: These results indicate that Progallin A has low
      immune toxicity in vitro and induces apoptosis of human hepatocellular carcinoma
      BEL-7404 cells which is related to the G1/M and G2/M arrest, and it exerts its
      apoptotic effect by up-regulation of Bax expression and down-regulation of Bcl-2
      expression.

PMID- 21073945
TI  - Anti-inflammatory effect of Ajuga bracteosa Wall Ex Benth. mediated through
      cyclooxygenase (COX) inhibition.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ajuga bracteosa Wall Ex Benth. (Labiateae) is
      described in Ayurveda for the treatment of rheumatism, gout, palsy and
      amenorrhea. AIM OF THE STUDY: The aim of present investigation is to study anti
      inflammatory activity of Ajuga bracteosa, to understand possible mechanism of
      action and to identify the constituents responsible for its activity. MATERIALS
      AND METHODS: The anti-inflammatory activity of 70% ethanolic extract was
      evaluated in TPA-induced mouse ear edema assay and in vitro cyclooxygenase (COX)
      1 and COX-2 inhibitory activity was determined using EIA kits employing
      appropriate reference standards. Aajugarin I, lupulin A, withaferin A, reptoside
      and 6-deoxyharpagide were isolated from the 70% ethanolic extract by silica gel
      column chromatography. RESULTS: The 70% ethanol extract of whole plants of Ajuga
      bracteosa showed a significant (p<0.05) and dose-dependent anti-inflammatory
      activity in an acute inflammation model at the dose of 0.5 and 1.0 mg/ear. The
      extract also exhibited a strong in vitro COX-1 and COX-2 inhibitory activity at
      25 and 50 MUg/mL concentration. Among the isolated compounds 6-deoxyharpagide
      exhibited highest COX-2 inhibition while rest of the compounds exhibited weak to
      moderate COX-1 and COX-2 inhibition at 30 MUM concentration. CONCLUSIONS: The
      results suggest that the 70% ethanol extract of Ajuga bracteosa possesses
      promising anti-inflammatory activity, which is possibly mediated through
      inhibition of COX-1 and COX-2 enzymes. The isolated constituents could be
      responsible in part for its anti-inflammatory and COX inhibitory activity. The
      study supports traditional use of Ajuga bracteosa for inflammatory diseases.

PMID- 21073946
TI  - Nitric oxide delivery system for biological media.
AB  - Developing an understanding of how chronically elevated levels of nitric oxide at
      sites of inflammation or infection can lead to cancer and other diseases requires
      ways to expose cells and biomolecules to controlled concentrations of NO for
      hours to days. To achieve this, a small (65ml) stirred reactor was fabricated
      that included a flat, porous poly(tetrafluoroethylene) membrane and a loop of
      poly(dimethylsiloxane) tubing for NO and O(2) delivery, respectively. It was
      equipped with probes for continuous monitoring of NO and O(2) concentrations.
      Transport through the membrane and tubing was characterized using separate O(2)
      depletion experiments. In experiments using only a 10% NO mixture and a buffer
      that was initially air-equilibrated, constant rates of accumulation were observed
      for NO(2)(-) (53+/-2MUM/h; n=8), the end product of NO oxidation, as expected.
      Simultaneous delivery of NO and O(2) yielded steady NO concentrations of 0.7
      2.3MUM, depending on the tubing length and gas compositions. A model was
      developed that allows the steady NO and O(2) concentrations and the duration of
      the transients to be predicted to within a few percent. This system should be
      useful for exposing cells and biomolecules to concentrations of NO that mimic
      those in vivo.

PMID- 21073947
TI  - Medical expenditures of children in the United States with fetal alcohol
      syndrome.
AB  - This paper calculates the medical expenditures for pediatric Medicaid enrollees
      with fetal alcohol syndrome (FAS), those with and those without reported
      intellectual disability (ID). The pediatric portion of the MarketScan(r) Medicaid
      Multi-State databases for the years 2003-2005 was used. Children with FAS were
      identified based on International Classification of Diseases, Ninth Revision,
      Clinical Modification codes. Children without FAS formed the comparison group.
      Annual mean, median, and 95(th) percentile total expenditures were calculated for
      those continuously enrolled during 2005. Children with FAS incurred annual mean
      medical expenditures that were nine times as high as those of children without
      FAS during 2005 ($16,782 vs. $1,859). ID more commonly was listed as a medical
      diagnosis among children with FAS than among children in the comparison group
      (12% vs. 0.5%), and mean expenditures of children with FAS and ID were 2.8 times
      those of children with FAS but without reported ID. Children with FAS incurred
      higher medical expenditures compared with children without FAS. A subset of
      children with FAS who had ID sufficiently serious to be recorded in medical
      records increased those expenditures still further. Our estimate of mean
      expenditures for children with FAS was several times higher than previous
      estimates in the United States.

PMID- 21073948
TI  - Nuclear receptor-driven alterations in bile acid and lipid metabolic pathways
      during gestation.
AB  - Nuclear receptor signalling is essential for physiological processes such as
      metabolism, development, and reproduction. Alterations in the endocrine state
      that naturally occur during pregnancy result in maternal adaptations to support
      the feto-placental unit. A series of studies have shown that nuclear receptor
      signalling is involved in maternal adaptations of bile acid, cholesterol, and
      lipid homeostasis pathways to ensure maintenance of the nutritional demands of
      the fetus. We discuss regulation of hepatic nuclear receptors and their target
      genes in pregnancy and their impact on the development of disorders such as
      intrahepatic cholestasis of pregnancy and oestrogen-induced hepatotoxicity. This
      article is part of a Special Issue entitled: Translating nuclear receptors from
      health to disease.

PMID- 21073949
TI  - Challenges in the development of hydrate phases as active pharmaceutical
      ingredients--an example.
AB  - The challenges during pilot plant scale-up of the SAR474832 API (active
      pharmaceutical ingredient) production in view of crystallization, isolation,
      drying and micronization are reported. A variety of different solid-state
      analytical and spectroscopic techniques (also coupled methods) were applied in
      order to understand the complex phase transition behaviour of the
      crystallographic phase (form 1) chosen for development: a partially non
      stoichiometric channel-hydrate (x (1+1.25) H(2)O) crystallizing from pure water
      in the crystal habit of fine needles, which tend to agglomerate upon isolation
      and drying. Processes have been developed for drying, sieving and micronization
      by jetmilling to avoid non-desired phase transitions (overdrying effects) into
      other hydrate forms. Special methods have been established to minimize, monitor
      and control the formation of amorphous content during the particle size reduction
      steps. By optimizing all production parameters it was possible to produce API
      batches in 10 kg scale with physical quality suitable for oral formulations (e.g.
      particle size d 90 value<20 MUm, water content and crystallographic phase
      corresponding to desired form 1 of SAR474832).

PMID- 21073950
TI  - Endocrine disrupting chemicals and other substances of concern in food contact
      materials: an updated review of exposure, effect and risk assessment.
AB  - Food contact materials (FCM) are an underestimated source of chemical food
      contaminants and a potentially relevant route of human exposure to endocrine
      disrupting chemicals (EDCs). Quantifying the exposure of the general population
      to substances from FCM relies on estimates of food consumption and leaching into
      food. Recent studies using polycarbonate plastics show that food simulants do not
      always predict worst-case leaching of bisphenol A, a common FCM substance. Also,
      exposure of children to FCM substances is not always realistically predicted
      using the common conventions and thus possibly misjudged. Further, the exposure
      of the whole population to substances leaching into dry foods is underestimated.
      Consumers are exposed to low levels of substances from FCM across their entire
      lives. Effects of these compounds currently are assessed with a focus on
      mutagenicity and genotoxicity. This approach however neglects integrating recent
      new toxicological findings, like endocrine disruption, mixture toxicity, and
      developmental toxicity. According to these new toxicology paradigms women of
      childbearing age and during pregnancy are a new sensitive population group
      requiring more attention. Furthermore, in overweight and obese persons a change
      in the metabolism of xenobiotics is observed, possibly implying that this group
      of consumers is insufficiently protected by current risk assessment practice.
      Innovations in FCM risk assessment should therefore include routine testing for
      EDCs and an assessment of the whole migrate toxicity of a food packaging, taking
      into account all sensitive population groups. In this article I focus on recent
      issues of interest concerning either exposure to or effects of FCM-related
      substances. Further, I review the use of benzophenones and organotins, two groups
      of known or suspected EDCs, in FCM authorized in the US and EU.

PMID- 21073951
TI  - Inhibitory mechanisms of the transcriptional activity of androgen receptor by
      resveratrol: Implication of DNA binding and acetylation of the receptor.
AB  - Androgen receptor (AR) is a ligand-dependent transcription factor and plays a key
      role in the development of prostate cancer. Resveratrol, a polyphenolic compound,
      inhibits AR function and reduces the level of prostate-specific antigen (PSA), a
      notable target gene of AR. Here, we investigated the mechanisms by which
      resveratrol inhibits AR function. Although the protein levels of AR were
      decreased by resveratrol treatment for 24h, the decrease could not fully account
      for the suppression of AR function. The total and the nuclear AR levels were not
      affected after incubation with 10MUM resveratrol for 3h, whereas resveratrol
      inhibited the binding of AR to the enhancer region of PSA and decreased the
      acetylation of AR even at this early phase. Inhibition of transcription by
      resveratrol was weaker in the AR acetylation site mutant than in the wild-type.
      In later phase (24h) after incubation with resveratrol, the ligand-induced
      nuclear accumulation of AR was markedly decreased by resveratrol. These data show
      that resveratrol inhibits DNA binding of AR, presumably by decreasing its level
      of acetylation and suggest that acetylation of AR is involved in its accumulation
      in the nucleus.

PMID- 21073952
TI  - Adoptive transfer of DNT cells induces long-term cardiac allograft survival and
      augments recipient CD4(+)Foxp3(+) Treg cell accumulation.
AB  - Regulatory T (Treg) cells play an important role in the regulation of immune
      responses but whether Treg will induce tolerance in transplant recipients in the
      clinic remains unknown. Our previous studies have shown that
      TCRalphabeta(+)CD3(+)CD4-CD8-NK1.1- (double negative, DN) T cells suppress T cell
      responses and prolong allograft survival in a single locus MHC-mismatched mouse
      model. In this study, we investigated the role of DNT cells in a more robust,
      fully MHC-mismatched BALB/c to C57BL/6 transplantation model, which may be more
      clinically relevant. Adoptive transfer of DNT cells in combination with short
      term rapamycin treatment (days 1-9) induced long-term heart allograft survival
      (101+/-31 vs. 39+/-13 days rapamycin alone, p<0.01). Furthermore adoptive
      transfer DNT cells augmented CD4+Foxp3+ Treg cells accumulation in transplant
      recipients while depletion of CD4(+) Treg cells by anti-CD25 inhibited the effect
      of DNT cells on long-term graft survival (48+/-12 days vs. 101+/-31 days,
      p<0.001). In conclusion, DNT cells combined with short-term immunosuppression can
      prolong allograft survival, which may be through the accumulation of
      CD4(+)Foxp3(+) Treg cells in the recipient. Our result suggests that allograft
      tolerance may require the co-existence of different type Treg cell phenotypes
      which are affected by current immunosuppression.

PMID- 21073953
TI  - CD28 blockade induces division-dependent downregulation of interleukin-2 receptor
      alpha.
AB  - BACKGROUND: Blockade of T cell costimulatory molecules represents a promising new
      method of attenuating donor-reactive T cell responses to promote graft survival
      following transplantation. However, recent studies in murine models have shown
      the presence of an initial high frequency of naive donor-reactive T cells may
      render this strategy ineffective. METHODS: In this report, we examined the
      phenotypic changes associated with CD28 blockade on T cells stimulated at
      increasing precursor frequencies in vitro. RESULTS: We found that treatment with
      the CD28 blocker CTLA-4 Ig resulted in downregulation of the alpha chain of the
      IL-2 receptor (CD25) in a division-dependent manner. Significantly, blockade of
      the CD28 pathway was more effective in down-regulating CD25 when the donor
      reactive T cell population was present at low as compared to high precursor
      frequency. CONCLUSIONS: These results imply that treatment with CD28 blockers and
      anti-CD25 mAbs may cooperate in promoting graft survival under conditions of low
      MHC matching where the donor-reactive T cell precursor frequency is high.

PMID- 21073954
TI  - Mechanisms underlying the diabetes-induced hyporeactivity of the rabbit carotid
      artery to atrial natriuretic peptide.
AB  - Atrial natriuretic peptide (ANP) plays an important role in the pathophysiology
      of the vascular complications in diabetes. The working hypothesis was that
      diabetes might modify the vascular actions of ANP in isolated rabbit carotid
      arteries and the mechanisms involved in these actions. ANP (10(-12)-10(-7)M)
      induced a relaxation of precontracted carotid arteries, which was lower in
      diabetic than in control rabbits. In arteries from both groups of animals,
      endothelium removal increased the ANP-induced relaxation. Isatin inhibited the
      relaxation to ANP both in arteries with and without endothelium. Carotid arteries
      from diabetic rabbits showed a decreased natriuretic peptide receptor (NPR)-A
      expression and an enhanced NPR-C expression. Inhibition of NO-synthesis did not
      modify ANP-induced relaxation in control rabbits but inhibited it in diabetic
      rabbits. In arteries with endothelium indomethacin enhanced the relaxation to ANP
      in control rabbits but did not modify it in diabetic rabbits. In endothelium
      denuded arteries indomethacin inhibited the relaxation to ANP in both groups of
      animals. In KCl-depolarised arteries, relaxation to ANP was almost abolished both
      in control and diabetic rabbits. Tetraethylammonium inhibited the relaxation to
      ANP, and this inhibition was higher in diabetic than in control rabbits. These
      results suggest that diabetes produces hyporeactivity of the rabbit carotid
      artery to ANP by a mechanism that at least includes a reduced expression of NPR
      A, an enhanced expression of NPR-C and a reduced participation of K(+)-channels.
      Furthermore, diabetes enhances endothelial NO release and diminishes the ratio
      thromboxane A(2)/prostacyclin. This increase of vasodilators could result from
      compensatory mechanisms counteracting the arterial hyporeactivity to ANP.

PMID- 21073955
TI  - Recent advances in macromolecular hydrodynamic modeling.
AB  - The modern implementation of the boundary element method [23] has ushered
      unprecedented accuracy and precision for the solution of the Stokes equations of
      hydrodynamics with stick boundary conditions. This article begins by reviewing
      computations with the program BEST of smooth surface objects such as ellipsoids,
      the dumbbell, and cylinders that demonstrate that the numerical solution of the
      integral equation formulation of hydrodynamics yields very high precision and
      accuracy. When BEST is used for macromolecular computations, the limiting factor
      becomes the definition of the molecular hydrodynamic surface and the implied
      effective solvation of the molecular surface. Studies on 49 different proteins,
      ranging in molecular weight from 9 to over 400kDa, have shown that a model using
      a 1.1A thick hydration layer describes all protein transport properties very well
      for the overwhelming majority of them. In addition, this data implies that the
      crystal structure is an excellent representation of the average solution
      structure for most of them. In order to investigate the origin of a handful of
      significant discrepancies in some multimeric proteins (about -20% observed in the
      intrinsic viscosity), the technique of Molecular Dynamics simulation (MD) has
      been incorporated into the research program. A preliminary study of dimeric alpha
      chymotrypsin using approximate implicit water MD is presented. In addition I
      describe the successful validation of modern protein force fields, ff03 and
      ff99SB, for the accurate computation of solution structure in explicit water
      simulation by comparison of trajectory ensemble average computed transport
      properties with experimental measurements. This work includes small proteins such
      as lysozyme, ribonuclease and ubiquitin using trajectories around 10ns duration.
      We have also studied a 150kDa flexible monoclonal IgG antibody, Trastuzumab, with
      multiple independent trajectories encompassing over 320ns of simulation. The
      close agreement within experimental error of the computed and measured properties
      allows us to conclude that MD does produce structures typical of those in
      solution, and that flexible molecules can be properly described using the method
      of ensemble averaging over a trajectory. We review similar work on the study of a
      transfer RNA molecule and DNA oligomers that demonstrate that within 3% a simple
      uniform hydration model 1.1A thick provides agreement with experiment for these
      nucleic acids. In the case of linear oligomers, the precision can be improved
      close to 1% by a non-uniform hydration model that hydrates mainly in the DNA
      grooves, in agreement with high resolution X-ray diffraction. We conclude with a
      vista on planned improvements for the BEST program to decrease its memory
      requirements and increase its speed without sacrificing accuracy.

PMID- 21073957
TI  - Multiple dense particle tracking in fluorescence microscopy images based on
      multidimensional assignment.
AB  - Multiple particle tracking (MPT) has seen numerous applications in live-cell
      imaging studies of subcellular dynamics. Establishing correspondence between
      particles in a sequence of frames with high particle density, particles merging
      and splitting, particles entering and exiting the frame, temporary particle
      disappearance, and an ill-performing detection algorithm is the most challenging
      part of MPT. Here we propose a tracking method based on multidimensional
      assignment to address these problems. We combine an Interacting Multiple Model
      (IMM) filter, multidimensional assignment, particle occlusion handling, and merge
      split event detection in a single software analysis package. The main advantage
      of a multidimensional assignment is that both spatial and temporal information
      can be used by using several later frames as reference. The IMM filter, which is
      used to maintain and predict the state of each track, contains several models
      which correspond to different types of biologically realistic movements. It works
      especially well with multidimensional assignment, because there tends to be a
      higher probability of correct particle association over time. First the method
      generates many particle-correspondence hypotheses, merge-split hypotheses and
      misdetection hypotheses within the framework of a sliding window over the frames
      of the image sequence. Then it builds a multidimensional assignment problem (MAP)
      accordingly. The particle is tracked with gap-filling, and merging and splitting
      events are then detected using the MAP solution. The tracking method is validated
      on both simulated tracks and microscopy image sequences. The results of these
      experiments show that the method is more accurate and robust than other "tracking
      from detected features" methods in dense particle situations.

PMID- 21073956
TI  - The substrate specificity of Metarhizium anisopliae and Bos taurus
      carboxypeptidases A: insights into their use as tools for the removal of affinity
      tags.
AB  - Carboxypeptidases may serve as tools for removal of C-terminal affinity tags. In
      the present study, we describe the expression and purification of an A-type
      carboxypeptidase from the fungal pathogen Metarhizium anisopliae (MeCPA) that has
      been genetically engineered to facilitate the removal of polyhistidine tags from
      the C-termini of recombinant proteins. A complete, systematic analysis of the
      specificity of MeCPA in comparison with that of bovine carboxypeptidase A (BoCPA)
      was carried out. Our results indicate that the specificity of the two enzymes is
      similar but not identical. Histidine residues are removed more efficiently by
      MeCPA. The very inefficient digestion of peptides with C-terminal lysine or
      arginine residues, along with the complete inability of the enzyme to remove a C
      terminal proline, suggests a strategy for designing C-terminal affinity tags that
      can be trimmed by MeCPA (or BoCPA) to produce a digestion product with a
      homogeneous endpoint.

PMID- 21073958
TI  - Role of distinct parietal areas in arithmetic: an fMRI-guided TMS study.
AB  - Although several parietal areas are known to be involved in number processing,
      their possible role in arithmetic operations remains debated. It has been
      hypothesized that the horizontal segment of the intraparietal sulcus (hIPS) and
      the posterior superior parietal lobule (PSPL) contribute to operations solved by
      calculation procedures, such as subtraction, but whether these areas are also
      involved in operations solved by memory retrieval, such as multiplication, is
      controversial. In the present study, we first identified the parietal areas
      involved in subtraction and multiplication by means of functional magnetic
      resonance imaging (fMRI) and we found an increased activation, bilaterally, in
      the hIPS and PSPL during both arithmetic operations. In order to test whether
      these areas are causally involved in subtraction and multiplication, we used
      transcranial magnetic stimulation (TMS) to create, in each participant, a virtual
      lesion of either the hIPS or PSPL, over the sites corresponding to the peaks of
      activation gathered in fMRI. When compared to a control site, we found an
      increase in response latencies in both operations after a virtual lesion of
      either the left or right hIPS, but not of the PSPL. Moreover, TMS over the hIPS
      increased the error rate in the multiplication task. The present results indicate
      that even operations solved by memory retrieval, such as multiplication, rely on
      the hIPS. In contrast, the PSPL seems to underlie processes that are nonessential
      to solve basic subtraction and multiplication problems.

PMID- 21073960
TI  - Small-world directed networks in the human brain: multivariate Granger causality
      analysis of resting-state fMRI.
AB  - Small-world organization is known to be a robust and consistent network
      architecture, and is a hallmark of the structurally and functionally connected
      human brain. However, it remains unknown if the same organization is present in
      directed influence brain networks whose connectivity is inferred by the transfer
      of information from one node to another. Here, we aimed to reveal the network
      architecture of the directed influence brain network using multivariate Granger
      causality analysis and graph theory on resting-state fMRI recordings. We found
      that some regions acted as pivotal hubs, either being influenced by or
      influencing other regions, and thus could be considered as information
      convergence regions. In addition, we observed that an exponentially truncated
      power law fits the topological distribution for the degree of total incoming and
      outgoing connectivity. Furthermore, we also found that this directed network has
      a modular structure. More importantly, according to our data, we suggest that the
      human brain directed influence network could have a prominent small-world
      topological property.

PMID- 21073959
TI  - Prefrontal cortical abnormalities in currently depressed versus currently
      remitted patients with major depressive disorder.
AB  - Previous neuromorphometric investigations of major depressive disorder (MDD) have
      reported abnormalities in gray matter in several regions, although the results
      have been inconsistent across studies. Some discrepancies in the results across
      studies may reflect design limitations such as small sample sizes, whereas others
      may reflect biological variability that potentially manifests as differences in
      clinical course. For example, it remains unclear whether the abnormalities found
      in persistently depressed MDD subjects extend to or persist in patients who
      experience prolonged remission. The aim of the present study was to investigate
      gray matter (GM) differences in unmedicated, currently-depressed participants
      (dMDD) and unmedicated, currently-remitted (rMDD) participants with MDD compared
      to healthy controls (HC). The GM density and volume were compared across groups
      using voxel-based morphometry, a quantitative neuroanatomical technique, and high
      resolution MRI images from 107 HC, 58 dMDD and 27 rMDD subjects. Relative to the
      HC group the dMDD group had reduced GM in the dorsal anterolateral (DALPFC), the
      dorsomedial (DMPFC) and the ventrolateral prefrontal cortex (VLPFC). Relative to
      the rMDD group the dMDD group showed reduced GM in the DALPFC, the VLPFC, the
      anterior cingulate cortex (ACC), the precuneus and the inferior parietal lobule.
      No regions were identified in which the rMDD group showed significantly lower GM
      compared to the HC group after p-values were corrected for the number of
      comparisons performed. In unmedicated patients in the depressed phase of MDD, we
      found evidence of morphometric abnormalities in DALPFC and in medial prefrontal
      cortical regions belonging to the visceromotor network. These findings, along
      with the absence of GM abnormalities in the remitted sample imply a possible link
      between greater GM tissue and better clinical outcome. Consistent with other
      neuroimaging and post-mortem neuropathological studies of MDD, we also found
      evidence of decreased white matter in patients with dMDD and rMDD.

PMID- 21073961
TI  - Visualization of cytoplasmic diffusion within living myelin sheaths of CNS white
      matter axons using microinjection of the fluorescent dye Lucifer Yellow.
AB  - The compactness of myelin allows for efficient insulation defining rapid
      propagation of action potentials, but also raises questions about how cytoplasmic
      access to its membranes is achieved, which is critical for physiological
      activity. Understanding the organization of cytoplasmic ('water') spaces of
      myelin is also important for diffusion MRI studies of CNS white matter. Using
      longitudinal slices of mature rat spinal cord, we monitored the diffusion of the
      water-soluble fluorescent dye Lucifer Yellow injected into individual
      oligodendrocytes or internodal myelin. We show that living myelin sheaths on CNS
      axons are fenestrated by a network of diffusionally interconnected cytoplasmic
      'pockets' (1.9 +/- 0.2 pockets per 10MUm sheath length, n=58) that included
      Schmidt-Lanterman clefts (SLCs) and numerous smaller compartments. 3-D
      reconstructions of these cytoplasmic networks show that the outer cytoplasmic
      layer of CNS myelin is cylindrically 'encuffing', which differs from EM studies
      using fixed tissue. SLCs were found in different 'open states' and remained
      stable within a 1-2hour observation period. Unlike the peripheral nervous system,
      where similarly small (<500Da) molecules diffuse along the whole myelin segment
      within a few minutes, in mature CNS this takes more than one hour. The slower
      cytoplasmic diffusion in CNS myelin possibly contributes to its known
      vulnerability to injury and limited capacity for repair. Our findings point to an
      elaborate cytoplasmic access to compact CNS myelin. These results could be of
      relevance to MRI studies of CNS white matter and to CNS repair/regeneration
      strategies.

PMID- 21073962
TI  - Cortico-striatal connectivity and cognition in normal aging: a combined DTI and
      resting state fMRI study.
AB  - Resting state fMRI studies have found that cognitive decline in aging is
      associated with alterations in functional connectivity of distributed neural
      systems in the brain. While functional connections have been shown to rely on the
      underlying structural connectivity, direct structural connections have been
      studied in only a few distributed cortical systems so far. It is well known that
      subcortical nuclei have structural connections to the entire cortex. We
      hypothesized that structural subcortico-cortical connections may provide integral
      routes for communication between cortical resting state networks, and that
      changes in the integrity of these connections have a role in cognitive aging. We
      combined anatomical MRI, diffusion tensor MRI, and resting state fMRI in 100
      healthy elderly to identify fiber bundles connecting cortical resting state
      networks to subcortical nuclei. In identified tracts, white matter fiber bundle
      integrity measures were compared to composite cognitive measures on executive
      function, processing speed, and memory performance. The integrity (FA values) in
      selected fiber bundles correlated strongly with cognitive measures on executive
      function and processing speed. Correlation was most pronounced between executive
      function and fiber bundles connecting the putamen to the dorsal attention network
      (r=0.73, p<0.001). Our findings show that unique cortico-subcortical fiber
      bundles can be identified for a range of cortical resting state networks, and
      indicate that these connections play an important role in cortical resting state
      network communication and cognition.

PMID- 21073963
TI  - Physiological noise effects on the flip angle selection in BOLD fMRI.
AB  - This work addresses the choice of imaging flip angle in blood oxygenation level
      dependent (BOLD) functional magnetic resonance imaging (fMRI). When noise of
      physiological origin becomes the dominant noise source in fMRI timeseries, it
      causes a nonlinear dependence of the temporal signal-to-noise ratio (TSNR) versus
      signal-to-noise ratio (SNR) that can be exploited to perform BOLD fMRI at angles
      well below the Ernst angle without any detrimental effect on our ability to
      detect sites of neuronal activation. We show, both experimentally and
      theoretically, that for situations where available SNR is high and physiological
      noise dominates over system/thermal noise, although TSNR still reaches it maximum
      for the Ernst angle, reduction of imaging flip angle well below this angle
      results in negligible loss in TSNR. Moreover, we provide a way to compute a
      suggested imaging flip angle, which constitutes a conservative estimate of the
      minimum flip angle that can be used under given experimental SNR and
      physiological noise levels. For our experimental conditions, this suggested angle
      equals 7.63 degrees  for the grey matter compartment, while the Ernst angle=77
      degrees . Finally, using data from eight subjects with a combined visual-motor
      task we show that imaging at angles as low as 9 degrees  introduces no
      significant differences in observed hemodynamic response time-course, contrast-to
      noise ratio, voxel-wise effect size or statistical maps of activation as compared
      to imaging at 75 degrees  (an angle close to the Ernst angle). These results
      suggest that using low flip angles in BOLD fMRI experimentation to obtain
      benefits such as (1) reduction of RF power, (2) limitation of apparent T(1)
      related inflow effects, (3) reduction of through-plane motion artifacts, (4)
      lower levels of physiological noise, and (5) improved tissue contrast is feasible
      when physiological noise dominates and SNR is high.

PMID- 21073964
TI  - Where in-vivo imaging meets cytoarchitectonics: the relationship between cortical
      thickness and neuronal density measured with high-resolution [18F]flumazenil-PET.
AB  - MRI-based measurements of surface cortical thickness (SCT) have become a
      sensitive tool to quantify changes in cortical morphology. When comparing SCT to
      histological cortical thickness maps, a good correspondence can be found for many
      but not all human brain areas. Discrepancies especially arise in the sensory
      motor cortex, where histological cortical thickness is high, but SCT is very low.
      The aim of this study was to determine whether the relationship between cortical
      thickness and neuronal density is the same for different cytoarchitectonic areas
      throughout homo- and heterotypical isocortex. We assessed this relationship using
      high-resolution [(18)F]-labelled flumazenil (FMZ) PET and SCT-mapping. FMZ binds
      to the benzodiazepine GABA(A) receptor complex which is localized on axo
      dendritic synapses, with a cortical distribution closely following the local
      density of neurons. SCT and voxelwise FMZ binding potential (BP(ND)) were
      assessed in ten healthy subjects. After partial volume correction, two subsets
      with a differential relationship between SCT and BP(ND) were identified: a fronto
      parietal homotypical subset where neuronal density is relatively constant and
      mainly independent of SCT, and a subset comprising heterotypical and mainly
      temporal and occipital homotypical regions where neuronal density is negatively
      correlated with SCT. This is the first in-vivo study demonstrating a differential
      relationship between SCT, neuronal density and cytoarchitectonics in humans.
      These findings are of direct relevance for the correct interpretation of SCT
      based morphometry studies, in that there is no simple relationship between
      apparent cortical thickness and neuronal density, here attributed to FMZ binding,
      holding for all cortical regions.

PMID- 21073965
TI  - Preterm birth results in alterations in neural connectivity at age 16 years.
AB  - Very low birth weight preterm (PT) children are at high risk for brain injury.
      Employing diffusion tensor imaging (DTI), we tested the hypothesis that PT
      adolescents would demonstrate microstructural white matter disorganization
      relative to term controls at 16 years of age. Forty-four PT subjects (600-1250 g
      birth weight) without neonatal brain injury and 41 term controls were evaluated
      at age 16 years with DTI, the Wechsler Intelligence Scale for Children-III
      (WISC), the Peabody Picture Vocabulary Test-Revised (PPVT), and the Comprehensive
      Test of Phonological Processing (CTOPP). PT subjects scored lower than term
      subjects on WISC full scale (p=0.003), verbal (p=0.043), and performance IQ tests
      (p=0.001), as well as CTOPP phonological awareness (p=0.004), but scored
      comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had
      lower fractional anisotropy (FA) values in multiple regions including bilateral
      uncinate fasciculi (left: p=0.01; right: p=0.004), bilateral external capsules
      (left: p<0.001; right: p<0.001), the splenium of the corpus callosum (p=0.008),
      and white matter serving the inferior frontal gyrus bilaterally (left: p<0.001;
      right: p=0.011). FA values in both the left and right uncinate fasciculi
      correlated with PPVT scores (a semantic language task) in the PT subjects (left:
      r=0.314, p=0.038; right: r=0.336, p=0.026). FA values in the left and right
      arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task)
      in the PT subjects (left: r=0.424, p=0.004; right: r=0.301, p=0.047). These data
      support for the first time that dual pathways underlying language function are
      present in PT adolescents. The striking bilateral dorsal correlations for the PT
      group suggest that prematurely born subjects rely more heavily on the right
      hemisphere than typically developing adults for performance of phonological
      language tasks. These findings may represent either a delay in maturation or the
      engagement of alternative neural pathways for language in the developing PT
      brain.

PMID- 21073966
TI  - Thalamocortical changes in major depression probed by deconvolution and
      physiology-based modeling.
AB  - Auditory event-related potentials (ERPs) have been extensively studied in
      patients with depression, but most studies have focused on purely
      phenomenological analysis methods, such as component scoring. In contrast, this
      study applies two recently developed physiology-based methods-fitting using a
      thalamocortical model of neuronal activity and waveform deconvolution - to data
      from a selective-attention task in four subject groups (49 patients with
      melancholic depression, 34 patients with non-melancholic depression, 111
      participants with subclinical depressed mood, and 98 healthy controls), to yield
      insight into physiological differences in attentional processing between
      participants with major depression and controls. This approach found evidence
      that: participants with depressed mood, regardless of clinical status, shift from
      excitation in the thalamocortical system towards inhibition; that clinically
      depressed participants have decreased relative response amplitude between target
      and standard waveforms; and that patients with melancholic depression also have
      increased thalamocortical delays. These findings suggest possible physiological
      mechanisms underlying different depression subtypes, and may eventually prove
      useful in motivating new physiology-based diagnostic methods.

PMID- 21073967
TI  - Functional segregation of the human cingulate cortex is confirmed by functional
      connectivity based neuroanatomical parcellation.
AB  - The four-region model with 7 specified subregions represents a theoretical
      construct of functionally segregated divisions of the cingulate cortex based on
      integrated neurobiological assessments. Under this framework, we aimed to
      investigate the functional specialization of the human cingulate cortex by
      analyzing the resting-state functional connectivity (FC) of each subregion from a
      network perspective. In 20 healthy subjects we systematically investigated the FC
      patterns of the bilateral subgenual (sACC) and pregenual (pACC) anterior
      cingulate cortices, anterior (aMCC) and posterior (pMCC) midcingulate cortices,
      dorsal (dPCC) and ventral (vPCC) posterior cingulate cortices and retrosplenial
      cortices (RSC). We found that each cingulate subregion was specifically
      integrated in the predescribed functional networks and showed anti-correlated
      resting-state fluctuations. The sACC and pACC were involved in an affective
      network and anti-correlated with the sensorimotor and cognitive networks, while
      the pACC also correlated with the default-mode network and anti-correlated with
      the visual network. In the midcingulate cortex, however, the aMCC was correlated
      with the cognitive and sensorimotor networks and anti-correlated with the visual,
      affective and default-mode networks, whereas the pMCC only correlated with the
      sensorimotor network and anti-correlated with the cognitive and visual networks.
      The dPCC and vPCC involved in the default-mode network and anti-correlated with
      the sensorimotor, cognitive and visual networks, in contrast, the RSC was mainly
      correlated with the PCC and thalamus. Based on a strong hypothesis driven
      approach of anatomical partitions of the cingulate cortex, we could confirm their
      segregation in terms of functional neuroanatomy, as suggested earlier by task
      studies or exploratory multi-seed investigations.

PMID- 21073968
TI  - The generation of tetrahedral mesh models for neuroanatomical MRI.
AB  - In this article, we describe a detailed method for automatically generating
      tetrahedral meshes from 3D images having multiple region labels. An adaptively
      sized tetrahedral mesh modeling approach is described that is capable of
      producing meshes conforming precisely to the voxelized regions in the image.
      Efficient tetrahedral mesh improvement is then performed minimizing an energy
      function containing three terms: a smoothing term to remove the voxelization, a
      fidelity term to maintain continuity with the image data, and a novel elasticity
      term to prevent the tetrahedra from becoming flattened or inverted as the mesh
      deforms while allowing the voxelization to be removed entirely. The meshing
      algorithm is applied to structural MR image data that has been automatically
      segmented into 56 neuroanatomical sub-divisions as well as on two other examples.
      The resulting tetrahedral representation has several desirable properties such as
      tetrahedra with dihedral angles away from 0 and 180 degrees, smoothness, and a
      high resolution. Tetrahedral modeling via the approach described here has
      applications in modeling brain structure in normal as well as diseased brain in
      human and non-human data and facilitates examination of 3D object deformations
      resulting from neurological illness (e.g. Alzheimer's disease), development,
      and/or aging.

PMID- 21073969
TI  - Performance comparison of machine learning algorithms and number of independent
      components used in fMRI decoding of belief vs. disbelief.
AB  - Machine learning (ML) has become a popular tool for mining functional
      neuroimaging data, and there are now hopes of performing such analyses
      efficiently in real-time. Towards this goal, we compared accuracy of six
      different ML algorithms applied to neuroimaging data of persons engaged in a
      bivariate task, asserting their belief or disbelief of a variety of propositional
      statements. We performed unsupervised dimension reduction and automated feature
      extraction using independent component (IC) analysis and extracted IC time
      courses. Optimization of classification hyperparameters across each classifier
      occurred prior to assessment. Maximum accuracy was achieved at 92% for Random
      Forest, followed by 91% for AdaBoost, 89% for Naive Bayes, 87% for a J48 decision
      tree, 86% for K*, and 84% for support vector machine. For real-time decoding
      applications, finding a parsimonious subset of diagnostic ICs might be useful. We
      used a forward search technique to sequentially add ranked ICs to the feature
      subspace. For the current data set, we determined that approximately six ICs
      represented a meaningful basis set for classification. We then projected these
      six IC spatial maps forward onto a later scanning session within subject. We then
      applied the optimized ML algorithms to these new data instances, and found that
      classification accuracy results were reproducible. Additionally, we compared our
      classification method to our previously published general linear model results on
      this same data set. The highest ranked IC spatial maps show similarity to brain
      regions associated with contrasts for belief > disbelief, and disbelief < belief.

PMID- 21073970
TI  - Congruence of happy and sad emotion in music and faces modifies cortical
      audiovisual activation.
AB  - BACKGROUND: The powerful emotion inducing properties of music are well-known, yet
      music may convey differing emotional responses depending on environmental
      factors. We hypothesized that neural mechanisms involved in listening to music
      may differ when presented together with visual stimuli that conveyed the same
      emotion as the music when compared to visual stimuli with incongruent emotional
      content. METHODS: We designed this study to determine the effect of auditory
      (happy and sad instrumental music) and visual stimuli (happy and sad faces)
      congruent or incongruent for emotional content on audiovisual processing using
      fMRI blood oxygenation level-dependent (BOLD) signal contrast. The experiment was
      conducted in the context of a conventional block-design experiment. A block
      consisted of three emotional ON periods, music alone (happy or sad music), face
      alone (happy or sad faces), and music combined with faces where the music excerpt
      was played while presenting either congruent emotional faces or incongruent
      emotional faces. RESULTS: We found activity in the superior temporal gyrus (STG)
      and fusiform gyrus (FG) to be differentially modulated by music and faces
      depending on the congruence of emotional content. There was a greater BOLD
      response in STG when the emotion signaled by the music and faces was congruent.
      Furthermore, the magnitude of these changes differed for happy congruence and sad
      congruence, i.e., the activation of STG when happy music was presented with happy
      faces was greater than the activation seen when sad music was presented with sad
      faces. In contrast, incongruent stimuli diminished the BOLD response in STG and
      elicited greater signal change in bilateral FG. Behavioral testing supplemented
      these findings by showing that subject ratings of emotion in faces were
      influenced by emotion in music. When presented with happy music, happy faces were
      rated as more happy (p=0.051) and sad faces were rated as less sad (p=0.030).
      When presented with sad music, happy faces were rated as less happy (p=0.008) and
      sad faces were rated as sadder (p=0.002). INTERPRETATION: Happy-sad congruence
      across modalities may enhance activity in auditory regions while incongruence
      appears to impact the perception of visual affect, leading to increased
      activation in face processing regions such as the FG. We suggest that greater
      understanding of the neural bases of happy-sad congruence across modalities can
      shed light on basic mechanisms of affective perception and experience and may
      lead to novel insights in the study of emotion regulation and therapeutic use of
      music.

PMID- 21073971
TI  - Ciproxifan, an H3 receptor antagonist, alleviates hyperactivity and cognitive
      deficits in the APP Tg2576 mouse model of Alzheimer's disease.
AB  - Previous research has indicated that the blockade of H(3)-type histamine
      receptors may improve attention and memory in normal rodents. The purpose of this
      study was to determine if ciproxifan, an H(3) receptor antagonist, could
      alleviate the hyperactivity and cognitive deficits observed in a transgenic mouse
      model (APP(Tg2576)) of Alzheimer's disease. APP(Tg2576) mice displayed
      significantly greater locomotor activity than wild-type mice, but APP(Tg2576)
      mice provided with daily ciproxifan treatment showed activity levels that did not
      differ from wild-type mice. In the swim maze, APP(Tg2576) mice exhibited
      significantly longer escape latencies, but the APP(Tg2576) mice treated daily
      with ciproxifan had latencies that were indistinguishable from controls. In probe
      trials conducted one hour after the last training trial, ciproxifan-treated
      APP(Tg2576) mice spent more time near the previous platform location and made
      more crossings of this area than did saline-treated APP(Tg2576) mice. APP(Tg2576)
      mice also demonstrated a significant impairment in the object recognition task
      that was reversed by acute treatment with ciproxifan (3.0mg/kg). These data
      support the idea that modulation of H(3) receptors represents a novel and viable
      therapeutic strategy in the treatment of Alzheimer's disease.

PMID- 21073972
TI  - The bed nucleus of the stria terminalis is required for the expression of
      contextual but not auditory freezing in rats with basolateral amygdala lesions.
AB  - Previous data suggest that overtraining can overcome fear conditioning deficits
      in rats with lesions of the basolateral complex of the amygdala (BLA). We have
      previously shown that the central nucleus of the amygdala (CEA) is essential for
      the acquisition and expression of conditional fear to both contextual and
      auditory conditioned stimuli (CSs) after overtraining. This provides strong
      evidence that the CEA can compensate for the loss of the BLA. Another brain area
      that may compensate for the loss of the BLA is the bed nucleus of the stria
      terminalis (BNST). We explored this possibility by examining the consequences of
      lesions or reversible inactivation of the BNST on the expression of overtrained
      fear in rats with BLA lesions. We demonstrate that lesions or inactivation of the
      BNST block the expression of freezing to the conditioning context, but not to an
      auditory conditional stimulus. These results reveal that the BNST has a critical
      role in the expression of contextual fear, but not fear to an auditory CS, and is
      therefore not the essential locus of compensation for fear learning in the
      absence of the BLA.

PMID- 21073973
TI  - Inside the Thompson laboratory during the "cerebellar years" and the continuing
      cerebellar story.
AB  - This paper is based on the talk by one of the authors (DL) given at the symposium
      for the retirement of RF Thompson (RF Thompson: A bridge between 20th and 21st
      century neuroscience). We first make some informal observations of the historical
      times and research conditions in the Thompson laboratory when the cerebellum was
      found to play a critical role in eye lid classical conditioning, the "cerebellar
      years". These conditions influenced our collaborative international program on
      the phenomenon known as "transfer of training" or "savings". Our research shows
      that the appearance of "savings" is an artifact of the order of testing, and
      depends upon the functioning of the contralateral interpositus nucleus (IPN) in a
      way that is complementary to the role of the IPN in normal eyelid classical
      conditioning.

PMID- 21073974
TI  - Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation
      for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first
      complete response or first partial response.
AB  - Patients with follicular lymphoma (FL) typically experience an indolent course;
      however, the disease is rarely curable with conventional chemotherapy. Autologous
      hematopoietic cell transplantation (HCT) can extend progression-free survival
      (PFS) and overall survival (OS), but relapse is the primary cause of failure.
      Allogeneic HCT confers lower relapse rates due to a graft-versus-lymphoma effect.
      Reduced-intensity conditioning (RIC) allows the performance of allogeneic HCT
      with lower toxicity. The Blood and Marrow Transplant Clinical Trials Network
      conducted a prospective multicenter trial comparing these two strategies in
      patients with relapsed, chemotherapy-sensitive FL. Patients were assigned to a
      treatment arm based on the availability of an HLA-matched sibling donor (MSD).
      Those with an MSD underwent allogeneic HCT (n = 8) with the FCR preparative
      regimen (fludarabine, cyclophosphamide [Cy], rituximab [RTX]) and received
      tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis.
      Those without an MSD (n = 22) underwent mobilization with Cy, RTX, and filgrastim
      and received a conditioning regimen of either CBV (Cy, carmustine, Etoposide
      [VP16]) or total body irradiation with Cy and VP16. Patients undergoing
      autologous HCT received 4 doses of weekly maintenance RTX (375 mg/m2) starting on
      day +42 post-HCT. Sixteen patients were in complete remission, 10 patients were
      in partial remission, and 1 patient had stable disease after salvage therapy and
      before HCT. Median follow-up was 36 months (range, 1-51 months). OS was 73% in
      autologous HCT versus 100% in allogeneic HCT, and PFS was 63% in autologous HCT
      versus 86% in allogeneic HCT. No patient had grade II-IV acute GVHD; two patients
      developed extensive chronic GVHD. Three autologous recipients died from
      nonrelapse causes. This trial closed early because of slow accrual. We show that
      the FCR regimen is well tolerated, and that both allogeneic and autologous HCT
      result in promising 3-year OS and PFS in patients with relapsed FL.

PMID- 21073975
TI  - Acute gastrointestinal graft-versus-host disease in pediatric patients: serum
      albumin on day 5 from initiation of therapy correlates with nonrelapse mortality
      and overall survival.
AB  - The aim of the present study was to identify factors associated with the risk of
      development of gastrointestinal acute graft-versus-host disease (GI-aGVHD), as
      well as to evaluate the impact of various baseline parameters on response to
      treatment, nonrelapse mortality (NRM), and overall survival (OS) in pediatric
      patients with GI-aGVHD after allogeneic hematopoietic stem cell transplantation
      (allo-SCT). We retrospectively analyzed 300 pediatric patients who underwent allo
      SCT from HLA-matched related or volunteer unrelated donors in our institution. GI
      tract involvement was observed in 46 out of 133 patients with aGVHD grade II-IV.
      Severe aGVHD (grade III-IV) was more frequently observed among patients with GI
      aGVHD in comparison with patients without GI involvement (P < .001). Treatment
      with steroids resulted in durable responses in 22/46 patients; 14 additional
      patients responded to salvage therapy, whereas 10 were refractory to all
      treatments administered. Using Cox regression analysis, we observed that serum
      albumin level >= 3 mg/dL on day 5 after the initiation of therapy with steroids
      was statistically significantly associated with decreased hazard of NRM and
      improved OS (P = .021 and P = .026, respectively). In our study, serum albumin
      level, early (+ day 5) after the onset of steroids in patients with GI-aGVHD, was
      a predictor of treatment outcome. Prospective randomized trials need to be
      performed to verify the predictive significance of serum albumin and the need for
      early intensification of immunosuppressive treatment.

PMID- 21073976
TI  - FungiFun: a web-based application for functional categorization of fungal genes
      and proteins.
AB  - FungiFun assigns functional annotations to fungal genes or proteins and performs
      gene set enrichment analysis. Based on three different classification methods
      (FunCat, GO and KEGG), FungiFun categorizes genes and proteins for several fungal
      species on different levels of annotation detail. It is web-based and accessible
      to users without any programming skills. FungiFun is the first tool offering gene
      set enrichment analysis including the FunCat categorization. Two biological
      datasets for Aspergillus fumigatus and Candida albicans were analyzed using
      FungiFun, providing an overview of the usage and functions of the tool. FungiFun
      is freely accessible at https://www.omnifung.hki-jena.de/FungiFun/.

PMID- 21073977
TI  - Cleavage of resveratrol in fungi: characterization of the enzyme Rco1 from
      Ustilago maydis.
AB  - Ustilago maydis, the causative agent of corn smut disease, contains two genes
      encoding members of the carotenoid cleavage oxygenase family, a group of enzymes
      that cleave double bonds in different substrates. One of them, Cco1, was formerly
      identified as a beta-carotene cleaving enzyme. Here we elucidate the function of
      the protein encoded by the second gene, termed here as Ustilago maydis
      Resveratrol cleavage oxygenase 1 (Um Rco1). In vitro incubations of
      heterologously expressed and purified UM Rco1 with different carotenoid and
      stilbene substrates demonstrate that it cleaves the interphenyl Calpha-Cbeta
      double bond of the phytoalexin resveratrol and its derivative piceatannol. Um
      Rco1 exhibits a high degree of substrate specificity, as suggested by the lack of
      activity on carotenoids and the other resveratrol-related compounds tested. The
      activity of Um Rco1 was confirmed by incubation of U. maydis rco1 deletion and
      over-expression strains with resveratrol. Furthermore, treatment with resveratrol
      resulted in striking alterations of cell morphology. However, pathogenicity
      assays indicated that Um rco1 is largely dispensable for biotrophic development.
      Our work reveals Um Rco1 as the first eukaryotic resveratrol cleavage enzyme
      identified so far. Moreover, Um Rco1 represents a subfamily of fungal enzymes
      likely involved in the degradation of stilbene compounds, as suggested by the
      cleavage of resveratrol by homologs from Aspergillus fumigatus, Chaetomium
      globosum and Botryotinia fuckeliana.

PMID- 21073978
TI  - Molecular characterization of hepcidin AS-hepc2 and AS-hepc6 in black porgy
      (Acanthopagrus schlegelii): expression pattern responded to bacterial challenge
      and in vitro antimicrobial activity.
AB  - There are more diversified isoforms of the hepcidin gene that exist in fishes
      than in mammals, and elucidating the differences between these isoforms should
      provide insight into the functioning of hepcidin in fishes. In our study, AS
      hepc2 and AS-hepc6 hepcidin isoforms from black porgy were characterized for
      their in vivo expression patterns following bacterial challenge, and their in
      vitro antimicrobial activities against Gram-positive and Gram-negative bacteria
      as well as fungi. As a result, two isoforms were observed to be widely
      distributed in all the tissues tested. AS-hepc2 was a liver-expressed hepcidin
      peptide which was always highly more expressed in the liver than in the other
      tissues tested no matter whether this was before or after bacterial challenge. AS
      hepc6 was detected mainly in the head kidney and trunk kidney of normal fish,
      but, in the challenged fish, its expression involved more tissues than just the
      kidneys. The mature peptides of AS-hepc2 and AS-hepc6 were modeled for 3D
      structure and then synthesized for antimicrobial assay. AS-hepc6 had a wider
      antimicrobial spectrum than AS-hepc2 and, in particular, had more potent
      antifungal activity. Our study indicated that the two hepcidin isoforms had
      different characteristics in terms of their expression patterns and antimicrobial
      activity, and they were assumed to play an overlapping role in the innate immune
      system of black porgy against invading pathogens.

PMID- 21073979
TI  - Isolation and identification of pelteobagrin, a novel antimicrobial peptide from
      the skin mucus of yellow catfish (Pelteobagrus fulvidraco).
AB  - Fish skin mucus has recently been recognized to be a potential source of
      antimicrobial peptides, which provides the first line of defense against invading
      pathogens. This study reports the purification and characterization of a novel
      linear antimicrobial peptide, pelteobagrin, from the skin mucus of yellow catfish
      (Pelteobagrus fulvidraco, Richardson). Pelteobagrin is 20 amino acids in length
      (GKLNLFLSRLEILKLFVGAL) and shows no clear homology with any known bioactive
      peptides. MALDI-TOF MS indicated the molecular mass of the purified peptide was
      2244.4 Da, which is in good agreement with pelteobagrin's predicted molecular
      weight of 2244.8 Da. Pelteobagrin exhibited antibacterial activity against Gram
      positive and Gram-negative bacteria as well as fungi, and the activity was
      relatively salt-insensitive as it was not affected by NaCl concentrations of up
      to 137 mM. Moreover, pelteobagrin displayed no hemolytic activity to rabbit red
      blood cells. Transmission electron microscopy suggested that pelteobagrin might
      kill bacteria via acting on both the cell wall and the cytoplasmic membrane of
      bacteria. These results suggest that pelteobagrin might be involved in the innate
      defense system in yellow catfish.

PMID- 21073980
TI  - Genotoxic effects of two nickel-compounds in somatic cells of Drosophila
      melanogaster.
AB  - In view of the scarcely available information on the in vivo mutagenic and co
      mutagenic activity of nickel, the genotoxic potential of two nickel-compounds,
      nickel chloride (NiCl(2)) and nickel sulphate (NiSO(4)), was assessed in
      Drosophila melanogaster by measuring two different genetic endpoints. On the one
      hand, we used the wing-spot assay, which is based on the principle that the loss
      of heterozygosity of two suitable recessive markers, multiple wing hairs (mwh)
      and flare-3 (flr(3)), can lead to the formation of mutant clones in the imaginal
      disks of larval cells. On the other hand, the in vivo comet assay, which detects
      single- and double-strand DNA breaks, was also used with larval haemocytes. These
      cells offer several advantages: they are highly sensitive to genotoxic agents,
      the sampling and processing methodologies are quite simple and the level of basal
      DNA damage is relatively low. No significant increases in the frequencies of the
      three categories of mutant spots (i.e. small single spots, large single spots,
      and twin spots) were observed in the wing-spot assay; however, NiSO(4) induced
      significant dose-dependent increases in DNA damage in the comet assay. In
      addition, the combined treatments with gamma-radiation and NiCl(2) and NiSO(4)
      showed a slight but significant increase in the frequency of the three categories
      of mutant spots compared with the frequency induced by gamma-radiation alone,
      indicating that both nickel compounds have a synergistic interaction. These
      results support the assumption that both nickel compounds could act as co
      mutagens interfering with DNA-repair processes and that the in vivo comet assay
      is a sensitive and effective method for detecting the DNA damage induced by
      NiSO(4) in haemocytes of D. melanogaster.

PMID- 21073981
TI  - Preservation of micronutrients during rapeseed oil refining: a tool to optimize
      the health value of edible vegetable oils? Rationale and design of the Optim'Oils
      randomized clinical trial.
AB  - Numerous micronutrients naturally abundant in oilseeds prevent the risk of
      cardiovascular diseases by reducing cholesterolemia and oxidative stress. These
      micronutrients include phytosterols and various antioxidants such as polyphenols,
      tocopherols and coenzyme Q10/Q9 but most of them are lost during the oilseed oil
      refining. The main objective of the Optim'Oil project was to modify the processes
      of oil refining in order to reduce the lost of micronutrients. Two clinical
      trials (cross-over, monocentric, randomized, double-blind and controlled) were
      designed to investigate the effect of an optimized rapeseed oil 1) on
      cardiovascular biomarkers (long-term study) and 2) on oxidative stress parameters
      (post-prandial study). For the long-term study, 59 volunteers ingested daily 20 g
      of oil and 22 g of margarine (optimized or standard) for 2 periods of 3 weeks
      separated by a 3-week wash-out period. Blood samples were collected at the
      beginning and at the end of each period. For the post-prandial study, a sub-group
      of 16 volunteers came fasted at the laboratory and took 300 mL of a test meal
      containing 60% of the optimized or standard oils. Blood samples were collected
      before and during 6h after the test meal intake. In comparison with the standard
      oil and margarine, the optimized oil and margarine exhibit as expected an
      increased content of phytosterol (+22%), polyphenols (* 11), tocopherols (+131%)
      and coenzyme Q10/Q9 (+165%). Overall, conditions of this study were relevant to
      investigate the effect of the optimized rapeseed oil and margarine on the
      cardiovascular risk and the oxidative stress.

PMID- 21073982
TI  - Expression patterns of ABCG2, Bmi-1, Oct-3/4, and Yap in the developing mouse
      incisor.
AB  - Recent studies have demonstrated the existence of dental stem cells in the
      continuously growing tooth. However, much remains to be learned about the complex
      mechanism involving stem cells during tooth development. We determined the
      expression patterns of four stem cell markers ABCG2, Bmi-1, Oct-3/4, and Yap in
      the developing mouse incisors between embryonic day (E) 11 and postnatal day (PN)
      20. ABCG2 was localized strongly in the perivascular region of the incisor
      mesenchyme from E11 to PN20, and in the odontoblasts from E18 to PN20. Bmi-1 was
      expressed in both the dental epithelium and mesenchyme from E11 to E14. The
      expression of Bmi-1 was noticeably reduced at E16, and was restricted to the
      apical bud from E16 to PN20. Oct-3/4 was localized in the nucleus of the cells in
      the superficial layer and stellate reticulum within the dental epithelium from
      E11 to E14 and in the apical bud from E16 to PN20. Meanwhile, once the
      ameloblasts and odontoblasts began to appear at E16, they expressed Oct-3/4 in
      the cytoplasm. Yap was expressed in most of the basal cells of the incisor dental
      epithelium from E11 to E14, but was expressed mainly in the transit-amplifying
      (TA) cells within the basal cell layer from E16 to PN20. The unique and
      overlapping expression patterns of ABCG2, Bmi-1, Oct-3/4, and Yap suggest the
      independent and interactive functions of the four stem cell markers in the
      developing mouse incisor.

PMID- 21073983
TI  - Influence of codeine on lobeline-induced respiratory reflexes and sensations and
      on ventilation with exercise in healthy subjects.
AB  - In 15 healthy subjects, the effect of 60 mg oral codeine and placebo was examined
      on intravenously injected lobeline-elicited respiratory reflexes and sensations.
      Its influence was also studied on ventilation and appearance of distressful
      respiratory sensations with modest but incremental exercise. After placebo,
      tachypnoea and respiratory sensations were evoked with 12.1 +/- 1.9 MUg/kg of
      lobeline i.v. (mean threshold dose) and after codeine, by significantly higher
      doses i.e., 18.0 +/- 3.1 MUg/kg (P < 0.05). Additionally after codeine, in
      response to incremental doses of lobeline the respiratory reflex was notably
      attenuated and the magnitude of respiratory sensations, subdued. Dry cough seen
      in 66% of the subjects with suprathreshold doses of lobeline i.e., 22.0 +/- 3.4
      MUg/kg (mean), appeared post codeine, with significantly higher doses i.e., 27.0
      +/- 3.9 MUg/kg (mean) (P < 0.05) and in a fewer subjects (60%). Mean increase in
      minute ventilation at the end of 8 min of incremental treadmill walking after
      codeine was 21% less than after placebo (P < 0.05); 60% of the subjects continued
      to walk for an additional 4 min and the onset of respiratory discomfort was
      delayed by 1-5 min. This is the first report of an attenuation of lobeline
      elicited respiratory reflexes and sensations that are attributable to J receptors
      (pulmonary C fibres) by a pharmacological entity. It also suggests that codeine
      decreased these receptors' known contribution to respiratory augmentation and
      motor inhibition during exercise, which was seen as a delay in the onset of, and
      a decrease in the magnitude of respiratory discomfort during treadmill walking
      and an increase in the duration walked by more than half the subjects.

PMID- 21073984
TI  - Cartography of human diaphragmatic innervation: preliminary data.
AB  - In humans, anatomy indicates that the phrenic nerve mainly arises from the C4
      cervical root, with variable C3 and C5 contributions. How this translates into
      functional innervation is unknown. The diaphragm response to electrical
      stimulation of C3, C4 and C5 was described in three patients undergoing surgical
      laryngeal reinnervation with an upper phrenic root (surface chest electrodes at
      anterior, lateral and posterior sites; oesophageal and gastric pressures (Pes and
      Pga) to derive transdiaphragmatic pressure (Pdi)). Anatomically, the phrenic
      nerve predominantly originated from C4. Phrenic stimulation elicited motor
      responses at the three sites in the three patients, as did C4 stimulation. It
      produced Pdi values of 9, 11, and 14cmH(2)O in the three patients, respectively,
      vs. 9, 9, and 7cmH(2)O for C4. C3 stimulation produced modest Pdi responses,
      whereas C5 stimulation could produce Pdi responses close to those observed with
      C4 stimulation. These singular observations confirm the dominance of C4 in
      diaphragm innervation but suggest than C5 can be of importance.

PMID- 21073985
TI  - Conjugation of fibronectin onto three-dimensional porous scaffolds for vascular
      tissue engineering applications.
AB  - Tissue engineering scaffolds provide the three-dimensional (3-D) geometry and
      mechanical framework required for regulating cell behavior and facilitating
      tissue maturation. Unfortunately, most synthetic scaffolds lack the biological
      recognition motifs required for seeded cell interaction. In order to impart this
      recognition, synthetic scaffolds should possess appropriate biological
      functionality. Here, for the first time, we present a comprehensive study of
      fibronectin (FN) conjugation onto highly porous 3-D poly(carbonate) urethane
      scaffolds through grafted poly(acrylic acid) spacers on the urethane backbone.
      Scanning electron microscopy was used to ensure that the porous structures of the
      scaffolds were preserved throughout the multiple conjugation steps, and Fourier
      transform infrared spectroscopy was used to monitor the reaction progress.
      Toluidine blue staining revealed that increasing acrylic acid concentration and
      grafting time increased the number of poly(acrylic acid) groups incorporated.
      High resolution X-ray photoelectron spectroscopy studies of the scaffolds
      demonstrated an increase in nitrogen and sulfur due to FN conjugation.
      Immunofluorescence microscopy studies showed an even distribution of conjugated
      FN on the 3-D scaffolds. Cell culture studies using human coronary artery smooth
      muscle cells demonstrated that FN-conjugated scaffolds had improved cell
      attachment and infiltration depth compared with scaffolds without FN conjugation
      and with those scaffolds on which FN was merely adsorbed.

PMID- 21073987
TI  - Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated
      multiethnic American population.
AB  - More than 20 mutations of the Sequestosome 1 (SQSTM1) gene have been reported in
      patients of European descent affected by Paget's disease of bone (PDB). In this
      investigation, a systematic screening for SQSTM1 mutations was conducted in
      consecutively evaluated unrelated patients with phenotypical PDB living in the
      New York City area (NY, United States). Seventy unrelated PDB patients with a
      multiethnic background, mostly of Jewish, Italian American, and Western European
      ancestries, were recruited. Sequencing of exons 7 and 8 was performed on DNA
      samples isolated from peripheral blood. Seven patients (10%) had SQSTM1
      mutations, of which three had a family history of PDB. Four patients carried the
      C1215T (P392L) mutation, and three patients carried novel SQSTM1 missense
      mutations: T1085A (S349T), C1209T (A390V), and T1290A (L417Q) mutations. All PDB
      patients with SQSTM1 mutations had polyostotic involvement, and the mean number
      of affected bones was significantly higher in pagetic patient carriers of a
      SQSTM1 mutation when compared to non-mutated PDB patients (4.0 vs. 2.0,
      respectively; P = 0.003). Haplotype analysis in patient carriers of the P392L
      mutation revealed that all P392L mutations were carried by haplotype 2. The
      SQSTM1 mutation rate in unrelated American patients described in the present
      study was similar to that reported in European populations.

PMID- 21073986
TI  - Combined inhibition of the BMP pathway and the RANK-RANKL axis in a mixed
      lytic/blastic prostate cancer lesion.
AB  - The purpose of this study was to investigate the influence of combined inhibition
      of receptor activator of nuclear factor kappa-B ligand (RANKL) and bone
      morphogenetic protein (BMP) activity in a mixed lytic/blastic prostate cancer
      lesion in bone. Human prostate cancer cells (C4 2b) were injected into
      immunocompromised mice using an intratibial injection model to create mixed
      lytic/blastic lesions. RANK-Fc, a recombinant RANKL antagonist, was injected
      subcutaneously three times a week (10mg/kg) to inhibit RANKL and subsequent
      formation, function and survival of osteoclasts. Inhibition of BMP activity was
      achieved by transducing prostate cancer cells ex vivo with a retroviral vector
      expressing noggin (retronoggin; RN). There were three treatment groups (RANK-Fc
      treatment, RN treatment and combined RN and RANK-Fc treatment) and two control
      groups (untreated control and empty vector control for the RN treatment group).
      The progression of bone lesion and tumor growth was evaluated using plain
      radiographs, hindlimb tumor size, (18)F-Fluorodeoxyglucose and (18)F-fluoride
      micro PET-CT, histology and histomorphometry. Treatment with RANK-Fc alone
      inhibited osteolysis and transformed a mixed lytic/blastic lesion into an
      osteoblastic phenotype. Treatment with RN alone inhibited the osteoblastic
      component in a mixed lytic/blastic lesion and resulted in formation of smaller
      osteolytic bone lesion with smaller soft tissue size. The animals treated with
      both RN and RANK-Fc demonstrated delayed development of bone lesions, inhibition
      of osteolysis, small soft tissue tumors and preservation of bone architecture
      with less tumor induced new bone formation. This study suggests that combined
      inhibition of the RANKL and the BMP pathway may be an effective biologic therapy
      to inhibit the progression of established mixed lytic/blastic prostate cancer
      lesions in bone.

PMID- 21073988
TI  - Economic evaluation of infant and adolescent hepatitis B vaccination in the UK.
AB  - A Markov model of hepatitis B virus (HBV) disease progression in the UK estimated
      that 81% of predicted HBV-associated morbidity and mortality could be prevented
      by universal infant vaccination at a cost of approximately L 260,000 per QALY
      gained. Universal adolescent vaccination would be less effective (45% prevented)
      and less cost-effective (L 493,000 per QALY gained). Higher HBV incidence rates
      in males and intermediate/high risk ethnic populations meant it was approximately
      3 times more cost-effective to vaccinate these groups. At current vaccine costs a
      selective infant vaccination programme, based on vaccinating intermediate/high
      risk ethnic populations would not be considered cost effective. The threshold
      cost per vaccinated child at which the programme would be considered cost
      effective was investigated. Universal infant vaccination would be cost-effective
      if the average cost of vaccinating each child against HBV, including vaccine and
      administration costs of all doses, was less than L 4.09. Given the low cost of
      vaccination required to make a universal programme cost-effective the most
      feasible policy in the UK would be to use a suitably priced combined vaccine that
      included the other antigens in the current infant vaccination schedule.

PMID- 21073989
TI  - Protection against avian metapneumovirus subtype C in turkeys immunized via the
      respiratory tract with inactivated virus.
AB  - Avian metapneumovirus subtype C (aMPV/C) causes a severe upper respiratory tract
      (URT) infection in turkeys. Turkeys were inoculated oculonasally with inactivated
      aMPV/C adjuvanted with synthetic double-stranded RNA polyriboinosinic
      polyribocytidylic acid (Poly IC). Immunized turkeys had elevated numbers of
      mucosal IgA+ cells in the URT and increased levels of virus-specific IgG and IgA
      in the lachrymal fluid and IgG in the serum. After 7 or 21 days post
      immunization, turkeys were challenged oculonasally with pathogenic aMPV/C.
      Immunized groups were protected against respiratory lesions induced by the
      challenge virus. Further, the viral copy number of the challenge virus in the URT
      were significantly lower in the immunized turkeys than in the unimmunized turkeys
      (P<0.05). These results showed that inactivated aMPV/C administered by the
      respiratory route induced protective immunity against pathogenic virus challenge.

PMID- 21073990
TI  - Innate immunity in HIV infection and implications for vaccine design: a summary
      of the workshop held at the National Institute of Allergy and Infectious
      Diseases, Bethesda on February 25-26, 2010.
AB  - The search for an effective HIV vaccine continues to be a challenge. Several
      candidates have been tested in preclinical protocols, and a few have been tested
      in clinical trials without resounding success. It is unclear why vaccine
      approaches to control HIV infection have been unsuccessful, but opportunities to
      dissect the causes for the failure have surfaced from recent work on the
      virology, immunology and pathogenesis of HIV and from analysis of vaccine
      studies. The significance of the innate immune system in HIV infection may
      provide new paths to discover effective approaches. This report summarizes a
      workshop held to discuss the role of selected aspects of innate immunity to viral
      infections and successful vaccines that may have important implications for
      designing effective HIV vaccines.

PMID- 21073991
TI  - Dual targets guided screening and isolation of Kukoamine B as a novel natural
      anti-sepsis agent from traditional Chinese herb Cortex lycii.
AB  - Treating sepsis remains challenging at present. Bacterial lipopolysaccharide
      (LPS) and bacterial DNA/CpG DNA are important pathogenic molecules and drug
      targets for sepsis. It is thus a promising strategy to treat sepsis by
      discovering agents that neutralize LPS and CpG DNA simultaneously. In this study,
      we present evidences of the biosensor based screening and isolation of active
      anti-sepsis fractions and monomers from traditional Chinese herbs using dual
      targets (LPS and CpG DNA) guided drug discovery strategy. Firstly, LPS or CpG DNA
      was immobilized on surfaces of cuvettes in the biosensor to establish a screening
      platform. Then, Cortex lycii with both highest affinities was selected out from
      one hundred and fourteen traditional Chinese herbs. In subsequent experiments,
      chromatography was utilized and coupled with the biosensor to purify fractions
      with a higher affinity for LPS and CpG DNA. In line with affinity assay, these
      fractions were shown to neutralize LPS and CpG DNA and inhibit their activity in
      vitro and in vivo. Lastly, the contributing monomer Kukoamine B (KB) was
      purified. KB neutralized LPS and CpG DNA in vitro. It inhibited TLR4, TLR9 and
      MyD88 mRNA expressions up-regulated by LPS and CpG DNA, and also attenuated the
      LPS and CpG DNA elicited nuclear translocation of NF-kappaB p65 protein in
      RAW264.7 cells. It also protected mice from lethal challenge of heat-killed E.
      coli, a mixture of LPS and CpG DNA. In conclusion, we presented a dual target
      guided discovery of a novel anti-sepsis agent KB from traditional Chinese herbs
      via combination of biosensor technology and chromatography methods.

PMID- 21073992
TI  - Drugs involved in drug-facilitated crimes--part II: Drugs of abuse, prescription
      and over-the-counter medications. A review.
AB  - In recent years, there has been a notable increase in the number of reports of
      drug-facilitated crimes. Usually, individuals report that they were robbed or
      assaulted while incapacitated by drugs. Most often, these cases have involved
      drugs that have the ability to produce an effect that leaves the victim in a
      semiconscious or unconscious state. It is reasonable to assume that the purpose
      of drug-induced incapacitation is probably largely unchanged with time. This
      covers the full range of property offences (particularly theft) and crimes
      against the person (often sexual assault). What have changed are the drugs
      themselves: the number; type; their accessibility; effects and detection. This
      review describes the different aspects related to the involvement and use of
      drugs of abuse, as well as prescription and over-the counter medications in drug
      facilitated crimes, which may help people working in this field to expand their
      knowledge in order to better understand the nature of these crimes or offences.

PMID- 21073993
TI  - [Current perspectives on the repackaging and stability of solid oral doses].
AB  - Which are the guidelines and scientific aspects for repackaged oral solid
      medications in France in 2010 whereas it develops? The transient or definitive
      displacement of the solid oral form from the original atmosphere to enter a
      repackaging process, sometimes automated, is likely to play a primary role in the
      controversy. However, the solid oral dose is to be repackaged in materials with
      defined quality. Considering these data, a review of the literature for
      determination of conditions for repackaged drug stability according to different
      international guidelines is presented in this paper. Attention is also paid to
      the defined conditions ensuring the conservation and handling of theses drugs
      throughout the repackaging process. However, there is lack of scientific
      published stability data. Nevertheless, recent alternatives may be proposed to
      overcome the complexity of studying stability in such conditions. Then, the
      comparison of the moisture barrier properties of the respective package, a
      galenic model of hygroscopic molecules, or light sensitive molecules or stability
      data obtained during the industrial preformulation phase could also secure the
      list of drugs to be reconditioned. Similarly, a wise precaution will be to get
      stability data for the industrial blisters and unit doses undergoing the real
      conditions of the medication use process in hospitals and other healthcare
      settings. By now, reduction of dispensing errors and improvement of the
      compliance aid put a different perspective on the problem of repackaged drugs. To
      date, the pharmacist is advised to carry out its analysis of the risks.

PMID- 21073994
TI  - [Two new anticoagulants available in 2010--Dabigatran Etexilate and Rivaroxaban:
      expected progresses--raised problems].
AB  - After having been used for decades, heparins (unfractionated heparin [UFH] or low
      molecular weight heparins [LMWH]) and vitamin K antagonists (VKA), which are only
      parenterally active or which are responsible for frequent iatrogenicity
      respectively, have to face the competition of new anticoagulant drugs targeting
      either factor Xa or factor IIa (thrombin). Rivaroxaban (Xarelto((r))) and
      Dabigatran Etexilate (Pradaxa((r))) are the two leading components. They are more
      convenient to use and do not require routine coagulation monitoring. They are
      already marketed for venous thromboembolism prevention in major orthopaedic
      surgery. Although manufacturers claim that no biological monitoring is required,
      these two compounds may interfere in routine coagulation tests such as PT or
      aPTT, and in esoteric assays such as anti-Xa activity (the results of which are
      usually expressed in international anti-Xa units either UFH or LMWH unit) for
      Rivaroxaban or anti-IIa activity for Dabigatran Etexilate. Noteworthy is the fact
      that, in the case of these new anticoagulant drugs, results should be expressed
      in active product units (nanogram per millilitre of Rivaroxaban or Dabigatran).
      The new anticoagulants are associated with a bleeding risk comparable to that of
      VKA and heparins.

PMID- 21073995
TI  - [The malaria vaccine candidate RTS,S/AS is in phase III clinical trials].
AB  - This review paper describes the development of the RTS,S/AS vaccine, from concept
      to phase III testing. The rationale for selection of the circumsporozoite protein
      (CSP) as the target antigen and the preclinical development history of the
      vaccine are described. The RTS,S/AS candidate vaccine has been evaluated in
      multiple phase I/II studies and was shown to have a favorable safety profile and
      to be well tolerated in both adults and children. Consistent and significant
      efficacy has been observed in the target population of infants and children
      against Plasmodium falciparum infection and disease in different transmission
      settings, in different age groups, with or without Expanded Program of
      Immunization (EPI) vaccine co-administration. The RTS,S/AS01(E) malaria vaccine
      candidate has recently entered phase III testing. Reaching this important
      milestone is the culmination of more than 20 years of research and development by
      GlaxoSmithKline, their partners and collaborators. If the phase III results
      confirm the observations made during phase II testing, the RTS,S/AS01(E) vaccine,
      when broadly implemented and judiciously integrated with other malaria-prevention
      measures, would have a major public-health impact in sub-Saharan Africa.

PMID- 21073996
TI  - [Direct cost of cataract surgery in public hospital].
AB  - INTRODUCTION: With more than 500,000 operations per year, cataract surgery is the
      most performed act nowadays in France. Several techniques can be used but the
      phacoemulsification after micro-incision is the most common and the purpose is to
      put an intraocular lens into the eye. AIM: To approach the direct cost of the
      cataract surgery and to compare it to the amounts of reimbursements, and to get
      some epidemiological and statistical data about this surgery. MATERIAL AND
      METHODS: This study is prospective; many operations were followed up in the
      operating room and every following data were recorded: age of the patient, type
      of anaesthesia, type of intraocular lens, adverse events, name of surgeon,
      duration of the intervention, single use material and medications used during
      operation and their quantity for each operation. RESULTS: One hundred and twenty
      five cataract surgeries were followed. Patients mean age was 74,1 years and the
      anaesthesia was topical in 87,2% of cases; only two patients had general
      anaesthesia. The mean duration was 42 minutes. The mean direct cost was 366 ? but
      reached 630 ? in case of capsular tear. The cost greatly varied depending on the
      surgeon. Two references of lens (foldable monofocal, that cost between 100 and
      150 ?) represented 80% of the implanted lenses. CONCLUSION: This type of study
      may lead to a standardisation of surgical techniques and evaluate the proportion
      of supply and medications in that type of surgery.

PMID- 21073997
TI  - [Reversible metalation of a bis-disulfide analogue of the Cys*-X-Cys* hepcidin
      binding site: structural characterisation of the related copper complex].
AB  - Hepcidin, a 25-amino-acid peptide secreted by the liver, distributed in the
      plasma and excreted in urine, is a key central regulator of body iron
      homeostasis. This hormone decreases export of cellular iron by binding to
      ferroportin, an iron exporter present at the basolateral surface of enterocytes
      and macrophages (the sites of dietary iron absorption and iron recycling,
      respectively), inducing its internalization and degradation. Hepcidin contains
      eight cysteine residues that form four disulfide bridges, which stabilize a
      hairpin-shaped structure with two beta sheets. We noticed in the sequence of
      hepcidin a Cys*-X-Cys* motif which can act as a metal binding site able to trap
      iron and/or copper. We have tested this hypothesis using a pseudopeptidic
      synthetic bis-disulfide analogue and we have shown that direct metalation of such
      ligand leads to the formation of a copper(III) complex with the typical N(2)S(2)
      donor set. This compound crystallizes in the orthorhombic system, space group
      Imma. The Cu(III) configuration is square planar, built up from two carboximado-N
      and two thiolato-S donors. This complex is converted back to the bis-disulfide,
      with release of the copper salt, upon oxidation with iodine.

PMID- 21073999
TI  - Assessment of obsessive beliefs: Comparing individuals with obsessive-compulsive
      disorder to a medical sample.
AB  - Cognitive behavior models for Obsessive-Compulsive Disorder (OCD) are based
      currently on the presence of specific beliefs associated with the disorder. Among
      these beliefs are inflated responsibility, concerns over thought-action fusion,
      and overimportance of thoughts. The aim of this study was to compare scores from
      the subscales of the Obsessive Beliefs Questionnaire (OBQ-87), developed by the
      Obsessive-Compulsive Cognitions Working Group (OCCWG, 2001), in 24 patients from
      an OCD clinic (OCD) and 24 patients from a Medical Clinic (MC) for ambulatory and
      chronic diseases. All OCD patients were diagnosed using the SCID, and the OCD
      portion of the SCID was used to rule out patients with OCD from the MC group. The
      Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Dysfunctional Attitudes Scale
      (DAS) were also administered. The results indicated that, contrary to
      predictions, in the domains of Tolerance for Uncertainty, Threat estimation,
      Responsibility and Perfectionism, the MC group presented higher scores than the
      OCD group. The same findings occurred with DAS, which was significantly
      correlated with the OBQ. Possible explanations for these findings are discussed,
      as well as suggestions for future research with both groups.

PMID- 21074000
TI  - Effects of acceptance-based coping on task performance and subjective stress.
AB  - This paper examines the interactive effects of acceptance-based coping and job
      control on task performance, subjective stress, and perceived control. Forty
      eight undergraduate and graduate students first participated in brief educational
      programs based on either acceptance or control coping strategies. They then
      participated in a 30-min high workload task under either high or low job control
      conditions. The results demonstrated a significant interactive effect of
      acceptance-based coping and job control on perceived control and task
      performance. No such effect was found for subjective stress. We conclude that to
      improve employees' perceived control and job performance, there should be an
      increase not only in job control through work redesign, but also in psychological
      acceptance.

PMID- 21074001
TI  - Resilience to depressive symptoms: The buffering effects of enhancing cognitive
      style and positive life events.
AB  - BACKGROUND AND OBJECTIVES: There are two lines of research examining the role of
      cognition in depression. One line of research focuses on risk for depression, and
      shows that a negative cognitive style interacts with stressful life events to
      create depression. The second line of research focuses on recovery, and shows
      that an enhancing cognitive style interacts with positive life events to reduce
      depression. The goal of this study was to integrate these two areas and provide a
      more comprehensive test of the cognitive model of depression. METHODS: A 4-week
      prospective longitudinal design was used to test the interaction between
      cognitive style (both negative and enhancing) and life events (both negative and
      positive) in a sample of undergraduates (n = 128). RESULTS: Cognitively
      vulnerable individuals were buffered from the depressive effects of stress if
      they also possessed an enhancing cognitive style or experienced high numbers of
      positive life events. Individuals with low levels of negative cognitive style and
      life stress, but high levels of enhancing cognitive style or positive life events
      were the most resilient to depressive symptoms. LIMITATIONS: Future research is
      needed to determine if the results of this study generalize to a more diverse
      sample as well as to clinically significant forms of depression. CONCLUSIONS: The
      results provide some of the first evidence for the protective role of enhancing
      cognitive style and positive live events among vulnerable individuals. These
      findings underscore the importance of examining a broader environmental context
      when investigating risk and resiliency to depression.

PMID- 21074002
TI  - Fear- and disgust-related covariation bias and eating disorders symptoms in
      healthy young women.
AB  - Covariation bias refers to the phenomenon of overestimating the contingency
      between certain stimuli and negative outcomes, which is considered as a heuristic
      playing a role in the maintenance of certain types of psychopathology. In the
      present study, an attempt was made to investigate covariation bias within the
      context of eating pathology. In a sample of 61 female undergraduates, a priori
      and a posteriori contingencies were measured between pictures of obese and slim
      bodies, on the one hand, and fear- or disgust-relevant outcomes, on the other
      hand. Results indicated that participants in general displayed an a priori and an
      a posteriori covariation bias reflecting an overestimation of the link between
      obese bodies and disgust-relevant outcomes. However, this bias was not related to
      eating disorder symptomatology. Meanwhile, eating pathology was positively
      associated with a priori covariation biases referring to the associations between
      obese bodies and fear-relevant outcomes, and between slim bodies and disgust
      relevant outcomes. All in all, these findings suggest that covariation bias plays
      a role in eating pathology.

PMID- 21074003
TI  - Autobiographical memory following cognitive behaviour therapy for complicated
      grief.
AB  - A deficit in the ability to retrieve specific autobiographical memories has been
      linked to a number of negative consequences, including poor problem solving
      skills, reduced ability to imagine the future, and the onset of symptoms
      following trauma. This study investigated the impact of cognitive behaviour
      therapy (CBT) on memory retrieval specificity in patients with Complicated Grief
      (CG). Twenty individuals with CG who were seeking treatment were administered an
      autobiographical memory task (AMT) before and after completing a 10-week CBT
      program. Pre-treatment retrieval specificity did not predict treatment outcome.
      However, there was a significant correlation between symptom reduction and
      increased specific retrieval to positive cues following treatment. These results
      suggest that overgeneral retrieval in CG can be modified by CBT, and may point to
      one means by which CBT can alleviate CG symptoms.

PMID- 21074004
TI  - Taxing working memory reduces vividness and emotional intensity of images about
      the Queen's Day tragedy.
AB  - Eye movements during exposure to distressing mental images reduce their vividness
      and emotional intensity, which may be due to both tasks competing for working
      memory (WM) resources. WM theory predicts an inverted U-shaped relationship
      between degree of taxing and beneficial effects: greater taxing of WM will more
      greatly reduce vividness/emotionality, but extremely taxing tasks prevent holding
      the image in mind, thereby reducing benefits. This study examined whether mental
      arithmetic (subtraction) tasks during visual imagery reduce image
      vividness/emotionality ratings, and taxing WM and reduced vividness/emotionality
      show the predicted quadratic relationship. A non-clinical sample retrieved a
      distressing image of the Queen's Day tragedy (which occurred 1-3 months earlier
      in the Netherlands), and rated it for vividness and emotionality. Participants
      were assigned to one of four conditions: exposure alone or exposure with
      concurrent 'simple' subtraction, 'intermediate' subtraction, or 'complex'
      subtraction. Afterwards, vividness and emotionality were rated again. A reaction
      time task showed that the subtraction tasks increasingly taxed WM. Consistent
      with WM theory, exposure with subtraction reduced image vividness and
      emotionality compared to exposure alone. The expected inverse U-curve
      relationship was found for emotionality, but not for vividness: simple or
      intermediate subtraction had more beneficial effects than no dual-task or complex
      subtraction. Clinical implications are discussed.

PMID- 21074005
TI  - Dysfunctional core beliefs, perceived parenting behavior and psychopathology in
      gender identity disorder: A comparison of male-to-female, female-to-male
      transsexual and nontranssexual control subjects.
AB  - BACKGROUND: Research into the association between Gender Identity Disorder (GID)
      and psychological disturbances as well as on its relation with parenting
      experiences yielded mixed results, with different patterns for Male-to-Female
      (MF) and Female-to-Male (FM) transsexual subjects. We investigated vulnerability
      markers of maladjustment and their possible origins in MF and FM transsexuals by
      examining maladaptive core beliefs and parenting behaviors thought to be
      specifically related to them. METHODS: Dysfunctional core beliefs, parenting
      experiences and psychiatric symptoms were assessed by the Young Schema
      Questionnaire indexing 19 Early Maladaptive Schemas (EMS), the Young Parenting
      Inventory and the Symptom Checklist-90-R, respectively, in 30 MF, 17 FM
      transsexual and 114 control subjects (43 males, 114 females). RESULTS: Subjects
      with GID demonstrated a level of psychiatric distress comparable to that of
      controls. They did display elevated scores, however, on multiple EMSs compared to
      nontranssexual subjects, indicating feelings of isolation, emotional deprivation
      and an urge to meet others' needs, with MF transsexuals conceptualizing
      themselves also as more vulnerable and deficient than controls. Parenting
      experiences of transsexual subjects were characterised by increased maternal
      dominance, emotional abuse and neglect compared to controls, with males being
      exposed to a disengaged maternal style and more paternal emotional neglect and
      criticism. Both MF and FM transsexuals were made felt that in areas of
      achievement they will inevitably fail. CONCLUSIONS: There is no evidence of
      elevated levels of psychiatric symptoms in GID, but potential predisposing
      factors, particularly in MF transsexuals, are present; these may originate from
      the more intense rejection they experience.

PMID- 21074006
TI  - The influence of state anxiety on the acquisition and extinction of fear.
AB  - OBJECTIVE: Fear conditionability has been found to be elevated in samples with
      high trait anxiety or anxiety disorders. Since these studies provide
      circumstantial evidence for a causal link between anxiety and conditionability we
      examined fear conditionability after experimental induction of anxiety in two
      experiments. METHOD: In Experiment 1, 60 participants were randomized to one of
      two film conditions inducing an anxious or happy emotional state. They
      subsequently underwent a differential conditioning acquisition procedure. Two
      pictures of faces served as conditioned stimuli (CS+ and CS-), and an electric
      stimulus served as aversive unconditioned stimulus (US). In Experiment 2, after
      similar acquisition procedure as used in Experiment 1, 90 participants watched
      one of three films (anxious, neutral, happy) prior to an extinction procedure. In
      both studies, skin conductance response (SCR) served as measure of fearful
      responding. RESULTS: Conditioning was successful in both studies. In Experiment
      1, the anxious group exhibited decreased SCRs to both CS+ and CS- during
      acquisition. In Experiment 2, during extinction SCRs to both CSs were highest in
      the anxious group, intermediate in the neutral, and lowest in the happy group.
      DISCUSSION: State anxiety did not enhance conditionability during acquisition or
      reduce the extinction procedure. However, individuals in an anxious state show
      less responding during fear learning, but more responding during unlearning.
      Thus, our results suggest that state anxiety changes the sensitivity with which
      individuals react to stimuli presented in different contexts.

PMID- 21074007
TI  - Putting the pill to work.

PMID- 21074008
TI  - When uterine leiomyomas complicate uterine evacuation....

PMID- 21074009
TI  - If the condom doesn't fit, you must resize it.

PMID- 21074010
TI  - Effects of the levonorgestrel-releasing intrauterine system on cervical mucus
      quality and sperm penetrability.
AB  - BACKGROUND: In levonorgestrel intrauterine system (LNG-IUS) users, the prevention
      of sperm penetration through cervical mucus has not been demonstrated. STUDY
      DESIGN: Subjects were enrolled in an investigator-blinded study to compare
      quality and sperm penetrability of mid-cycle cervical mucus between LNG-IUS users
      and hormone-free controls. Cervical mucus was microscopically examined using
      World Health Organization (WHO) cervical mucus analysis (CMA). CMA score >=10 of
      15 points indicated cervical mucus favoring sperm penetration. Mucus was
      incubated with sperm using the WHO simplified slide test (SST) and Kremer sperm
      cervical mucus penetration test (SCMPT). RESULTS: Data from 14 LNG-IUS users and
      16 controls showed 14% of LNG-IUS users had CMA score >=10% vs. 69% of controls
      (p=.004). SST showed no sperm penetration for LNG-IUS users, significantly less
      than controls (0% vs. 64.3%, p<.001). SCMPT demonstrated no sperm mucus
      penetration for LNG-IUS users at 2 and 6 h (0% vs. 85% in controls with 2-h score
      >=6, p<.001; 6 h 0% vs. 79% in controls, p<.001). CONCLUSIONS: Mid-cycle cervical
      mucus of LNG-IUS users is poor quality and prevents endocervical sperm transport
      in vitro.

PMID- 21074011
TI  - Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol
      20 mcg based on 2 years of clinical trial data in Canada.
AB  - BACKGROUND: The study was conducted to evaluate bleeding profile and safety of
      continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl
      estradiol (EE) 20 mcg. STUDY DESIGN: Healthy women who participated at seven
      Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were
      eligible for this second-year extension study. Primary end points included
      bleeding profile and adverse events. RESULTS: Seventy-nine women enrolled without
      interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to
      cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence
      of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean
      (median) number of bleeding days for the last two 90-day intervals was 1.1 (0)
      and 0.7 (0) days, respectively. CONCLUSIONS: Continuous LNG 90 mcg/EE 20 mcg had
      a safety profile similar to low-dose cyclic OCs. Short-term safety profile
      remained excellent, with increasing rates of amenorrhea and decreasing incidence
      of unscheduled bleeding and/or spotting.

PMID- 21074012
TI  - Biopsychosocial variables associated with substantial bone mineral density loss
      during the use of depot medroxyprogesterone acetate in adolescents: adolescents
      who lost 5% or more from baseline vs. those who lost less than 5%.
AB  - BACKGROUND: It is unclear why some adolescents experience substantial bone
      mineral density (BMD) loss, while others experience a minimal decrease during
      depot medroxyprogesterone acetate (DMPA) use. We examined biopsychosocial factors
      in adolescents who experienced >=5% BMD loss from baseline compared with
      adolescents who experienced <5% BMD loss during DMPA use. STUDY DESIGN: A
      multicenter, prospective, nonrandomized study of 181 female adolescents who
      initiated DMPA for contraception was conducted. BMD (by dual-energy X-ray
      absorptiometry) and serum estradiol were measured at initiation and every 6
      months for 240 weeks of DMPA use. RESULTS: Half of participants experienced BMD
      loss of >=5% from baseline at the hip, and a quarter experienced BMD loss of >=5%
      at the lumbar spine (BMD substantial losers, SL). Hip and lumbar spine BMD-SL
      received a significantly greater number of DMPA injections than non-SL (p<.001).
      Decreased estradiol levels did not statistically differ between BMD loss
      subgroups. Hip BMD-SL had significantly lower baseline body mass index (BMI) than
      non-SL (p=.002), and there was an inverse relationship between weight gain and
      degree of BMD loss. Mean calcium intake was significantly lower (p<.05) in hip
      BMD-SL, and reported alcohol use was significantly higher (p<.05) in lumbar spine
      BMD-SL compared with non-SL. CONCLUSIONS: BMD loss of >=5% was more common at the
      hip than at the lumbar spine among adolescents using DMPA. Decreased serum
      estradiol levels did not correlate with magnitude of BMD loss. Lower BMI and
      calcium intake and greater alcohol use were associated with greater BMD loss in
      adolescents using DMPA.

PMID- 21074013
TI  - Comparison of 400 mcg buccal and 400 mcg sublingual misoprostol after
      mifepristone medical abortion through 63 days' LMP: a randomized controlled
      trial.
AB  - BACKGROUND: Buccal misoprostol 800 mcg and sublingual misoprostol 400 mcg
      demonstrate high efficacy and few adverse effects when used with 200 mg
      mifepristone for medical abortion through 63 days since the last menstrual period
      (LMP). Little is known about a 400-mcg buccal dose. This study compares two in
      the-mouth routes of misoprostol using the same dose. STUDY DESIGN: Eligible and
      consenting women (n=550) were randomized to 400 mcg of misoprostol buccally or
      sublingually 24 h after ingestion of 200 mg of mifepristone. Abortion status was
      assessed 2 weeks later. RESULTS: Complete abortion occurred in 97.1% of the
      buccal group and 97.4% of the sublingual group (p=.97, RR: 1.00, 95% CI=0.97
      1.03). Adverse effects were similar in both groups. Over 90% of women in both
      arms expressed high satisfaction with the method. CONCLUSIONS: Both 400 mcg
      buccal misoprostol and 400 mcg sublingual misoprostol after mifepristone appear
      to be good options for medical abortion through 63 days' LMP.

PMID- 21074014
TI  - A pilot study of the Copper T380A IUD and oral levonorgestrel for emergency
      contraception.
AB  - BACKGROUND: This study evaluates the willingness of women presenting for
      emergency contraception (EC) to enroll in a study offering the copper
      intrauterine device (IUD) or oral levonorgestrel (LNG) and follows up the two
      groups for 6 months after EC administration to compare use of an effective method
      of contraception. STUDY DESIGN: This prospective observational study offered
      these two methods to women presenting for EC. The primary outcome was use of an
      effective method of contraception 6 months after presenting for EC. RESULTS:
      Thirty-four women (60%) chose oral LNG and 23 (40%) chose the copper IUD. One
      month after presenting for EC, 21 (96%) of 22 in the IUD group were still using
      the IUD and all 22 were using an effective method of contraception (efficacy
      >=92%). In the LNG group, 13 (52%) of 25 were using an effective method of
      contraception (p<.001). At 6 months, 9 (69%) of 13 IUD users and 11 (52%) of 21
      oral LNG EC users were using an effective method (p=NS). CONCLUSION: Women
      presenting for EC were willing to enroll in a study offering the copper IUD or
      oral LNG.

PMID- 21074015
TI  - Hormonal evaluation and midcycle detection of intrauterine glycodelin in women
      treated with levonorgestrel as in emergency contraception.
AB  - BACKGROUND: The study was conducted to assess the effects of levonorgestrel (LNG)
      on hormonal behavior and on the secretory pattern of intrauterine glycodelin at
      the midcycle of ovulatory women. STUDY DESIGN: Thirty healthy sterilized women
      with normal ovarian function were studied during one control untreated cycle and
      one LNG-treated cycle. In the treated cycle, each woman received two doses of
      0.75 mg of LNG 12 h apart during the preovulatory phase approximately 2 days
      before the LH surge. Daily follicle development recordings were performed until
      follicle rupture was observed, and serum glycodelin, LH, estradiol, estrone and
      progesterone were measured as well. In addition, glycodelin concentrations were
      assayed in uterine flushing obtained on Days LH+1 and LH+12. RESULTS: LNG did not
      modify follicle rupture in 20 of 30 women. In spite of ovulatory progesterone and
      the occurrence of follicle rupture in these women, luteal phase length was
      significantly decreased, as well as the serum concentrations of LH, estradiol and
      estrone in the periovulatory phase. Glycodelin in serum and uterine flushings was
      significantly elevated in the periovulatory phase when compared to control
      cycles. CONCLUSIONS: LNG taken at the dose used in emergency contraception before
      the LH surge increased prematurely serum and intrauterine concentrations of
      glycodelin at the time of ovulation. Since there are well established glycodelin
      inhibitory effects upon fertilization, these results may represent an additional
      action of LNG in situations where the intervention did not interfere with
      ovulation.

PMID- 21074016
TI  - Cultural adaptation among Hispanic women as related to awareness and acquisition
      of emergency contraception.
AB  - BACKGROUND: The study was conducted to examine the relationship between cultural
      adaptation (acculturation), contraceptive use, personal history of induced
      abortion, and emergency contraceptive (EC) awareness and acquisition among a
      sample of young sexually active Hispanic women. STUDY DESIGN: A total of 959
      Hispanic women between 16 and 24 years of age (mean+/-SD 20.71+/-2.42 years)
      completed a survey containing questions on EC acquisition and awareness,
      acculturation, contraceptive used at last intercourse and history of induced
      abortion. Data were analyzed using logistic regression analyses. RESULTS:
      Acculturation (p=.017), income (p=.024) and education (p<.001) were positively
      associated with awareness of EC. Additionally, acculturation (p=.003) and a
      history of an induced abortion (p=.026) were positively associated with
      acquisition of EC. CONCLUSIONS: Educational programs should make an effort to
      include Hispanic women with lower acculturation levels as increasing their
      knowledge about EC use and its mechanism of action may greatly reduce the number
      of unplanned pregnancies in this population.

PMID- 21074017
TI  - Community pharmacists providing emergency contraception give little advice about
      future contraceptive use: a mystery shopper study.
AB  - BACKGROUND: UK women increasingly prefer to attend a pharmacy for emergency
      contraception (EC) rather than a doctor. Most women who use EC do not conceive
      and remain at risk of pregnancy unless they start regular contraception. We
      undertook a study to evaluate the quality of service provision in community
      pharmacies in Lothian, Scotland, and to determine what advice is given about
      contraception after EC use. STUDY DESIGN: Mystery shopper study. RESULTS: EC was
      unobtainable from 5/40 pharmacies (12.5%), refused because of "contraindications"
      in 7 (17.5%) and offered in 28 (70%). Most pharmacists appeared nonjudgemental,
      over 75% asked appropriate questions about eligibility, and over 90% gave
      appropriate advice about use. EC was universally refused beyond 72 h after sex
      but universally provided when the date of the last menstrual period was
      uncertain. Ongoing contraception after EC use was discussed in only 32.5% of all
      pharmacies and only 43% of those issuing EC. CONCLUSIONS: The quality of
      consultations for EC in pharmacies is generally good but only a minority discuss
      ongoing contraception after EC use. The implications for contraceptive use and
      unintended pregnancy rates are worrying.

PMID- 21074018
TI  - Contraceptive needs of women seeking care from a publicly funded sexually
      transmitted infection clinic.
AB  - OBJECTIVES: To determine the contraceptive needs [including emergency
      contraception (EC)] of women seeking care from a publicly funded sexually
      transmitted infection (STI) clinic and to better understand women's knowledge of
      and attitudes towards EC. METHODS: An anonymous survey was administered to 197
      women seeking services at one Chicago Department of Public Health STI clinic.
      RESULTS: After excluding women unlikely to become pregnant within the next year
      because of age, sexual orientation, hysterectomy and those who desired pregnancy
      (n=47), data from 150 women were available for analysis. Thirteen percent were
      using "very effective" contraception (intrauterine contraception, implant or
      sterilization) and 26% were using "effective" contraception (contraceptive pill,
      patch, ring or injectable). Approximately 23% (95% CI 16.5-30.0%) may have
      benefited from immediate use of EC as they reported at least one act of
      unprotected intercourse within the past 5 days. CONCLUSION: Many women seeking
      care from public STI clinics are at high risk of unintended pregnancy. A
      substantial number of women have an immediate need of EC at the time of their
      clinical visit. Efforts are needed to improve provision of EC as well as
      effective ongoing contraception for this population.

PMID- 21074019
TI  - Type of contraception method used at last intercourse and associations with
      health risk behaviors among US adolescents.
AB  - BACKGROUND: This study was conducted to examine associations with contraception
      methods used at last sexual intercourse among US adolescents. STUDY DESIGN: Data
      consisted of sexually active adolescents (9th-12th grade, weighted n=24,638) from
      the 1999-2007 Youth Risk Behavior Surveillance System (YRBSS). We performed
      multinomial multivariable logistic regression analyses with condom users at last
      sexual intercourse as the reference group. RESULTS: Males who used alcohol,
      cigarettes, marijuana and cocaine were more likely to use no method/unsure of
      method (OR=2.4, CI=1.7-3.4) or rely on withdrawal (OR=2.6, CI=1.5-4.3). Females
      with six or more sexual partners were more likely to rely on withdrawal (OR=2.9,
      CI=2.1-3.9) or contraception methods that offer no STI protection [i.e., birth
      control pills: OR=1.9, CI=1.4-2.5; and depot medroxyprogesterone acetate (DMPA,
      marketed as Depo-Provera): OR=2.6, CI=1.6-4.2]. Earlier age of sexual debut was
      also associated with nonuse. CONCLUSION: Prevention efforts should focus on at
      risk adolescents including substance-using males, females with six or more sexual
      partners, and those who initiate sexual intercourse at an early age.

PMID- 21074020
TI  - Evaluation of the effect of a patient decision aid about vasectomy on the
      decision-making process: a randomized trial.
AB  - BACKGROUND: Between 7% and 10% of men who choose vasectomy as a contraceptive
      method regret their decision. This study evaluates the effect of a patient
      decision aid (PtDA) designed to help men decide whether or not to have a
      vasectomy. STUDY DESIGN: Men considering vasectomy were randomized to an
      experimental group that received a full PtDA containing information and values
      guidance (n=32) or to a control group that received an abridged PtDA containing
      information only (n=31). RESULTS: Mean Decisional Conflict Scale (DCS) scores
      before and after the intervention were 2.6+/-0.4 and 1.9+/-0.4 in the
      experimental group and 2.5+/-0.4 and 1.8+/-0.4 in the control group (p=.94),
      respectively. Mean knowledge of vasectomy scores before and after the
      intervention were 50%+/-16% and 72%+/-18% in the experimental group and 55%+/-18%
      and 71%+/-15% in the control group (p=.40), respectively. At baseline, all
      participants were undecided as to whether to have a vasectomy. After the
      intervention, 60% of experimental group participants and 53% of control group
      participants had made a definite decision (p=.58). CONCLUSION: In men considering
      vasectomy, both versions of the PtDAs improved the quality of decision-making
      process to a similar extent. Information alone may be sufficient to support good
      decision making in these patients.

PMID- 21074021
TI  - Expanded safety and acceptability of the candidate vaginal microbicide
      Carraguard(r) in South Africa.
AB  - BACKGROUND: Carraguard's safety and acceptability was assessed among women in
      Gugulethu and Ga-Rankuwa, South Africa. STUDY DESIGN: A randomized, placebo
      controlled, triple-blind trial was conducted in HIV-negative, nonpregnant women
      who inserted Carraguard or placebo at least three times a week, including before
      vaginal sex, for 6 to 12 months. Monthly visits included pelvic examination,
      sexually transmitted infection (STI) testing/treatment and HIV
      counseling/testing. Acceptability was assessed quarterly. RESULTS: Of 400 women
      (205 Carraguard, 195 placebo) enrolled, 328 (77%) completed at least 6 months.
      Incidence of genital epithelial disruption was similar between the Carraguard
      (13.6 per 100 woman-years) and placebo (21.3 per 100 woman-years) groups
      (relative risk, 0.64; 95% confidence interval, 0.37-1.10); there were no
      significant differences in rates of HIV/STI, though the study was not powered to
      determine effectiveness. Only 2% of adverse events were judged possibly related
      to (either) gel. More than 94% of women reported at least once liking the gel
      very much. CONCLUSIONS: Carraguard was not associated with more vaginal, cervical
      or external genital irritation than placebo, and it was acceptable when used
      approximately 3.5 times per week, including during sex.

PMID- 21074022
TI  - Inhibition of vascular endothelial growth factor during the postovulatory period
      prevents pregnancy in the marmoset.
AB  - BACKGROUND: This study investigated the effects of inhibition of vascular
      endothelial growth factor (VEGF) during the first postpartum cycle in marmosets
      housed with a fertile male where a 90% fertility rate is normal. METHODS: On
      resumption of mating, females were treated with either 25 mg/kg aflibercept, a
      potent VEGF inhibitor, or control Fc protein (n=6 per group) at the time of
      ovulation. Effects on timing of pregnancy were monitored by measuring plasma
      progesterone, chorionic gonadotropin (CG) and uterine palpation. RESULTS: In five
      of six Fc-treated controls, the postpartum rise in progesterone was maintained
      and followed by a sustained rise in CG by Day 30 posttreatment indicating
      pregnancy. In all six aflibercept-treated animals, progesterone secretion was
      suppressed in the treatment cycle and a CG rise did not occur by Day 30.
      Pregnancy was delayed to the next cycle, significantly extending interbirth
      interval compared to controls. Posttreatment deliveries and infant development
      were normal. CONCLUSION: These results show that stringent pharmacological
      inhibition of VEGF suppresses luteal progesterone and prevents the successful
      establishment of pregnancy.

PMID- 21074023
TI  - Facing the facts on advance provision of emergency contraception.

PMID- 21074026
TI  - Capturing the sexual side effects of hormonal contraception.

PMID- 21074028
TI  - BMI, pharmacokinetics, and OCP failure.

PMID- 21074029
TI  - Wounds and wound healing. Foreword.

PMID- 21074030
TI  - Wounds and wound management. Preface.

PMID- 21074032
TI  - Wound healing primer.
AB  - Surgeons often care for patients with conditions of abnormal wound healing, which
      include conditions of excessive wound healing, such as fibrosis, adhesions, and
      contractures, as well as conditions of inadequate wound healing, such as chronic
      nonhealing ulcers, recurrent hernias, and wound dehiscences. Despite many recent
      advances in the field, which have highlighted the importance of adjunct therapies
      in maximizing the healing potential, conditions of abnormal wound healing
      continue to cause significant cost, morbidity, and mortality. To understand how
      conditions of abnormal wound healing can be corrected, it is important to first
      understand the basic principles of wound healing.

PMID- 21074031
TI  - Wound surgery.
AB  - The purpose of this article is to review the concepts behind, and practice of,
      wound surgery. The techniques of wound surgery, born of necessity in the art of
      military surgeons, have found their renaissance in the modern age of wound care
      driven by the economic and functional considerations inherent to the outcome
      based management of chronic disease. Over 300 years of literature on wound
      healing has shown an innate ability of the wound (in the absence of infection and
      repeated trauma) to control its progress, largely through the local inflammatory
      cells. This article discusses several historical works on wound surgery and
      healing, topical wound therapy, minimal intervention, and emphasizes the closure
      of chronic wounds.

PMID- 21074033
TI  - Current concepts regarding the effect of wound microbial ecology and biofilms on
      wound healing.
AB  - Biofilms are a collection of microbes that adhere to surfaces by manufacturing a
      matrix that shields them from environmental elements. Wound biofilms are
      difficult to evaluate clinically, and standard culture methods are inadequate for
      capturing the true bioburden present in the biofilm. New molecular techniques
      provide the means for rapid detection and evaluation of wound biofilms, and may
      prove to be useful in the clinical setting. Studies have shown that many
      commercial topical agents and wound dressings in use are ineffective against the
      biofilm matrix. At this stage, mechanical debridement appears to be essential in
      the eradication of a wound biofilm. Topical antimicrobial agents and antibiotics
      may be effective in the treatment of the wound bed after debridement in the
      prevention of biofilm reformation.

PMID- 21074035
TI  - Complex wounds and their management.
AB  - Complex wounds present a challenge to both the surgeon and patient in operative
      management, long-term care, cosmetic outcome, and effects on lifestyle, self
      image, and general health. Each patient with complex wounds usually manifests
      multiple risk factors for their development. This article focuses on complex
      wounds involved with traumatic and orthopedic blunt or penetrating injuries,
      particularly in the extremities, as well as massive soft tissue infections
      including necrotizing fasciitis, gas gangrene, and Fournier gangrene. The
      principles of management of complex wounds involve assessing the patient's
      clinical status and the wound itself, appropriate timing of intervention,
      providing antibiotic therapy when necessary, and planning and executing surgical
      therapy, including the establishment of a clean wound bed and
      closure/reconstructive strategies.

PMID- 21074036
TI  - Medical and surgical therapy for advanced chronic venous insufficiency.
AB  - Venous ulceration is the most serious consequence of chronic venous
      insufficiency. The disease has been known for more than 3.5 millennia with wound
      care centers established as early as 1500 bc. Unfortunately, still today it is a
      very poorly managed medical condition by most physicians despite that a great
      deal has been learned about the pathogenesis and treatment for venous
      ulcerations. We find that many wound care clinics treat the wound and not the
      cause of the problem. In this article, we review the basic pathophysiology of
      advanced chronic venous insufficiency and review the most up-to-date information
      with regard to medical therapy and different options of surgical therapy to
      address the underlying venous pathology responsible for chronic ulcers.

PMID- 21074034
TI  - Unusual causes of cutaneous ulceration.
AB  - Skin ulceration is a major source of morbidity and is often difficult to manage.
      Ulcers caused by an inflammatory cause or microvascular occlusion are
      particularly challenging in terms of diagnosis and treatment. The management of
      such ulcers requires careful assessment of associated systemic conditions and a
      thorough analysis of the ulcer's clinical and histologic findings. In this
      article, the authors discuss several examples of inflammatory ulcers and the
      approach to the diagnosis and treatment of these ulcers.

PMID- 21074037
TI  - Endovascular therapy for limb salvage.
AB  - In recent years percutaneous therapy has gradually been adopted as an alternative
      to primary amputation in persons deemed unsuitable as surgical candidates, and
      has established itself as a primary mode of treatment. There has been an
      explosion in endovascular technology and a revolution in revascularization
      patterns for limb salvage. Open surgery is now frequently reserved for failure of
      endovascular attempts or pathology unsuitable for endovascular revascularization.
      This article aims to educate the practicing general surgeon about the usefulness
      and appropriate application of different therapeutic endovascular options as
      applied to limb salvage.

PMID- 21074038
TI  - Intra-abdominal healing: gastrointestinal tract and adhesions.
AB  - The abdominal cavity represents one of the most active areas of surgical
      activity. Surgical procedures involving the gastrointestinal (GI) tract are among
      the most common procedures performed today. Healing of the GI tract after removal
      of a segment of bowel and healing of the peritoneal surfaces with subsequent
      adhesion formation remain vexing clinical problems. Interventions to modify both
      the responses are myriad, yet a full understanding of the pathophysiology of
      these responses remains elusive. Different aspects of GI and peritoneal healing,
      with associated factors, are discussed in this article.

PMID- 21074039
TI  - Active wound coverings: bioengineered skin and dermal substitutes.
AB  - Extensive skin loss and chronic wounds present a significant challenge to the
      clinician. With increased understanding of wound healing, cell biology, and cell
      culture techniques, various synthetic dressings and bioengineered skin
      substitutes have been developed. These materials can protect the wound, increase
      healing, provide overall wound coverage, and improve patient care. The ideal skin
      substitute may soon become a reality.

PMID- 21074040
TI  - Modeling Rett syndrome with stem cells.
AB  - The discovery that somatic cells can be reprogrammed into induced pluripotent
      stem cells (iPSCs) raised the exciting possibility of modeling diseases with
      patient-specific cells. Marchetto et al. (2010) now use iPSC technology to
      generate, characterize, and treat an in vitro model for the autism spectrum
      disorder Rett syndrome.

PMID- 21074041
TI  - Translation by remote control.
AB  - Efficient and accurate gene expression requires the coordination of multiple
      steps along the pathway of mRNA and protein synthesis. Now, Harel-Sharvit et al.
      (2010) show that transcriptional imprinting of mRNAs with two subunits of RNA
      polymerase II, Rbp4p and Rpb7p, guides transcripts to the translation apparatus.

PMID- 21074042
TI  - Shining a light on germinal center B cells.
AB  - The mechanisms of B cell selection in lymphoid tissues are poorly understood. In
      this issue, Victora et al. (2010) use imaging of photoactivatable green
      fluorescent protein to define the movements of B cells in germinal centers and
      provide evidence that antibody affinity maturation is driven by competition for T
      cell help.

PMID- 21074043
TI  - A straightjacket for pain?
AB  - Perception of pain involves both the peripheral and central nervous systems.
      Starting with a whole-genome RNA interference screen in Drosophila, Neely et al.
      (2010) identify a mammalian gene that is required not only for efficient transfer
      of pain signals between brain centers, but also for the suppression of
      inappropriate signaling between other sensory systems.

PMID- 21074044
TI  - Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues.
AB  - Direct reprogramming of somatic cells to induced pluripotent stem cells by
      ectopic expression of defined transcription factors has raised fundamental
      questions regarding the epigenetic stability of the differentiated cell state. In
      addition, evidence has accumulated that distinct states of pluripotency can
      interconvert through the modulation of both cell-intrinsic and exogenous factors.
      To fully realize the potential of in vitro reprogrammed cells, we need to
      understand the molecular and epigenetic determinants that convert one cell type
      into another. Here we review recent advances in this rapidly moving field and
      emphasize unresolved and controversial questions.

PMID- 21074045
TI  - A model for neural development and treatment of Rett syndrome using human induced
      pluripotent stem cells.
AB  - Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which
      different combinations of genetic mutations may contribute to the phenotype.
      Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system
      using induced pluripotent stem cells (iPSCs) from RTT patients' fibroblasts. RTT
      patients' iPSCs are able to undergo X-inactivation and generate functional
      neurons. Neurons derived from RTT-iPSCs had fewer synapses, reduced spine
      density, smaller soma size, altered calcium signaling and electrophysiological
      defects when compared to controls. Our data uncovered early alterations in
      developing human RTT neurons. Finally, we used RTT neurons to test the effects of
      drugs in rescuing synaptic defects. Our data provide evidence of an unexplored
      developmental window, before disease onset, in RTT syndrome where potential
      therapies could be successfully employed. Our model recapitulates early stages of
      a human neurodevelopmental disease and represents a promising cellular tool for
      drug screening, diagnosis and personalized treatment.

PMID- 21074046
TI  - Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to
      enable precise gene regulation.
AB  - Metazoan transcription is controlled through either coordinated recruitment of
      transcription machinery to the gene promoter or regulated pausing of RNA
      polymerase II (Pol II) in early elongation. We report that a striking difference
      between genes that use these distinct regulatory strategies lies in the "default"
      chromatin architecture specified by their DNA sequences. Pol II pausing is
      prominent at highly regulated genes whose sequences inherently disfavor
      nucleosome formation within the gene but favor occlusion of the promoter by
      nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing
      show higher nucleosome occupancy downstream, but their promoters are deprived of
      nucleosomes regardless of polymerase binding. Our results indicate that a key
      role of paused Pol II is to compete with nucleosomes for occupancy of highly
      regulated promoters, thereby preventing the formation of repressive chromatin
      architecture to facilitate further or future gene activation.

PMID- 21074047
TI  - RNA polymerase II subunits link transcription and mRNA decay to translation.
AB  - Little is known about crosstalk between the eukaryotic transcription and
      translation machineries that operate in different cell compartments. The yeast
      proteins Rpb4p and Rpb7p represent one such link as they form a heterodimer that
      shuttles between the nucleus, where it functions in transcription, and the
      cytoplasm, where it functions in the major mRNA decay pathways. Here we show that
      the Rpb4/7 heterodimer interacts physically and functionally with components of
      the translation initiation factor 3 (eIF3), and is required for efficient
      translation initiation. Efficient translation in the cytoplasm depends on
      association of Rpb4/7 with RNA polymerase II (Pol II) in the nucleus, leading to
      a model in which Pol II remotely controls translation. Hence, like in
      prokaryotes, the eukaryotic translation is coupled to transcription. We propose
      that Rpb4/7, through its interactions at each step in the mRNA lifecycle,
      represents a class of factors, "mRNA coordinators," which integrate the various
      stages of gene expression into a system.

PMID- 21074048
TI  - A family of protein-deglutamylating enzymes associated with neurodegeneration.
AB  - Polyglutamylation is a posttranslational modification that generates glutamate
      side chains on tubulins and other proteins. Although this modification has been
      shown to be reversible, little is known about the enzymes catalyzing
      deglutamylation. Here we describe the enzymatic mechanism of protein
      deglutamylation by members of the cytosolic carboxypeptidase (CCP) family. Three
      enzymes (CCP1, CCP4, and CCP6) catalyze the shortening of polyglutamate chains
      and a fourth (CCP5) specifically removes the branching point glutamates. In
      addition, CCP1, CCP4, and CCP6 also remove gene-encoded glutamates from the
      carboxyl termini of proteins. Accordingly, we show that these enzymes convert
      detyrosinated tubulin into Delta2-tubulin and also modify other substrates,
      including myosin light chain kinase 1. We further analyze Purkinje cell
      degeneration (pcd) mice that lack functional CCP1 and show that microtubule
      hyperglutamylation is directly linked to neurodegeneration. Taken together, our
      results reveal that controlling the length of the polyglutamate side chains on
      tubulin is critical for neuronal survival.

PMID- 21074049
TI  - Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase
      Hrd1p.
AB  - Misfolded, luminal endoplasmic reticulum (ER) proteins are retrotranslocated into
      the cytosol and degraded by the ubiquitin/proteasome system. This ERAD-L pathway
      requires a protein complex consisting of the ubiquitin ligase Hrd1p, which spans
      the ER membrane multiple times, and the membrane proteins Hrd3p, Usa1p, and
      Der1p. Here, we show that Hrd1p is the central membrane component in ERAD-L; its
      overexpression bypasses the need for the other components of the Hrd1p complex.
      Hrd1p function requires its oligomerization, which in wild-type cells is
      facilitated by Usa1p. Site-specific photocrosslinking indicates that, at early
      stages of retrotranslocation, Hrd1p interacts with a substrate segment close to
      the degradation signal. This interaction follows the delivery of substrate
      through other ERAD components, requires the presence of transmembrane segments of
      Hrd1p, and depends on both the ubiquitin ligase activity of Hrd1p and the
      function of the Cdc48p ATPase complex. Our results suggest a model for how Hrd1p
      promotes polypeptide movement through the ER membrane.

PMID- 21074051
TI  - Transcriptional regulation of ROS controls transition from proliferation to
      differentiation in the root.
AB  - The balance between cellular proliferation and differentiation is a key aspect of
      development in multicellular organisms. Using high-resolution expression data
      from the Arabidopsis root, we identified a transcription factor, UPBEAT1 (UPB1),
      that regulates this balance. Genomewide expression profiling coupled with ChIP
      chip analysis revealed that UPB1 directly regulates the expression of a set of
      peroxidases that modulate the balance of reactive oxygen species (ROS) between
      the zones of cell proliferation and the zone of cell elongation where
      differentiation begins. Disruption of UPB1 activity alters this ROS balance,
      leading to a delay in the onset of differentiation. Modulation of either ROS
      balance or peroxidase activity through chemical reagents affects the onset of
      differentiation in a manner consistent with the postulated UPB1 function. This
      pathway functions independently of auxin and cytokinin plant hormonal signaling.
      Comparison to ROS-regulated growth control in animals suggests that a similar
      mechanism is used in plants and animals.

PMID- 21074050
TI  - Germinal center dynamics revealed by multiphoton microscopy with a
      photoactivatable fluorescent reporter.
AB  - The germinal center (GC) reaction produces high-affinity antibodies by random
      mutation and selective clonal expansion of B cells with high-affinity receptors.
      The mechanism by which B cells are selected remains unclear, as does the role of
      the two anatomically defined areas of the GC, light zone (LZ) and dark zone (DZ).
      We combined a transgenic photoactivatable fluorescent protein tracer with
      multiphoton laser-scanning microscopy and flow cytometry to examine anatomically
      defined LZ and DZ B cells and GC selection. We find that B cell division is
      restricted to the DZ, with a net vector of B cell movement from the DZ to the LZ.
      The decision to return to the DZ and undergo clonal expansion is controlled by T
      helper cells in the GC LZ, which discern between LZ B cells based on the amount
      of antigen captured and presented. Thus, T cell help, and not direct competition
      for antigen, is the limiting factor in GC selection.

PMID- 21074053
TI  - Retraction notice to: Population-level transcription cycles derive from
      stochastic timing of single-cell transcription.

PMID- 21074054
TI  - Enhanced SnapShot: Macromolecular machines.

PMID- 21074052
TI  - A genome-wide Drosophila screen for heat nociception identifies alpha2delta3 as
      an evolutionarily conserved pain gene.
AB  - Worldwide, acute, and chronic pain affects 20% of the adult population and
      represents an enormous financial and emotional burden. Using genome-wide neuronal
      specific RNAi knockdown in Drosophila, we report a global screen for an innate
      behavior and identify hundreds of genes implicated in heat nociception, including
      the alpha2delta family calcium channel subunit straightjacket (stj). Mice mutant
      for the stj ortholog CACNA2D3 (alpha2delta3) also exhibit impaired behavioral
      heat pain sensitivity. In addition, in humans, alpha2delta3 SNP variants
      associate with reduced sensitivity to acute noxious heat and chronic back pain.
      Functional imaging in alpha2delta3 mutant mice revealed impaired transmission of
      thermal pain-evoked signals from the thalamus to higher-order pain centers.
      Intriguingly, in alpha2delta3 mutant mice, thermal pain and tactile stimulation
      triggered strong cross-activation, or synesthesia, of brain regions involved in
      vision, olfaction, and hearing.

PMID- 21074055
TI  - Recurrent early-stage triple-negative breast cancer.

PMID- 21074057
TI  - Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical
      background: CTLA-4 and PD-1 blockade.
AB  - Much of the recent excitement in the translational field of tumor immunology and
      immunotherapy has been generated by the recognition that immune checkpoint
      proteins can be blocked by human antibodies with profound effects in vitro, in
      animal tumor systems, and in patients. Promising clinical data have already been
      generated in melanoma and other tumor types with human antibodies directed
      against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1).
      The preclinical data that supported the clinical development of these two
      antibodies will be discussed in detail in this review, showing that many of the
      therapeutic effects of these two agents were predicted by the animal models, as
      were the immune-related side effects noted with these drugs. In contrast, much of
      the early work with anti-CTLA-4 antibodies indicated that it had a potent
      therapeutic effect only when combined with granulocyte-macrophage colony
      stimulating factor (GM-CSF)-transduced tumor vaccines, and that the antibody
      alone was effective only in the most immunogenic tumor models in mice.
      Intriguingly, in patients, the drug alone clearly has had important therapeutic
      effects, but the addition of vaccines has not added to its clinical benefit.
      Murine experiments also suggested that CTLA-4 abrogation might function via
      important effects on natural T-regulatory cells that were CD4(+), CD25(+high),
      and FOXp3(+), but this has not been borne out in experiments using peripheral
      blood mononuclear cells from patients treated with anti-CTLA-4 antibodies, and
      unlike in animals, in humans the exact mechanism(s) by which CTLA-4 abrogation
      induced an anti-tumor effect is still unclear. Abrogation of PD-1 functions via
      different immune signaling pathways than CTLA-4 and is likely to have a different
      spectrum of effects than blocking CTLA-4. For PD-1 blockade, murine experiments
      have suggested that the antibody alone and combined with adoptive cell transfer
      or vaccine approaches would be therapeutically beneficial, and that clear effects
      on T-cell proliferation and activation, as well as T-regulatory cell function
      would be observed in patients. The clinical development of anti-PD-1 antibody so
      far has shown that it has a potent effect when administered alone, and trials of
      vaccines with anti-PD-1 are just being initiated to test the idea that the
      predicted effects of that antibody observed in animal systems also would be seen
      in patients. These observations support the idea that animal preclinical
      therapeutic experiments are an important guide to the conduct of trials employing
      abrogation of immune checkpoint proteins in T cells in patients. Nonetheless,
      clinical investigators must be flexible and prepared to find that the biology of
      those systems may be very different in humans compared to mice.

PMID- 21074058
TI  - Ipilimumab: unleashing the power of the immune system through CTLA-4 blockade.
AB  - Malignant melanoma is rising faster in incidence than any other malignancy. Long
      term remission or "cure" is rare and is almost exclusively limited to therapies
      that stimulate an immune antitumor response. Ipilimumab is a novel targeted human
      immunostimulatory monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4
      (CTLA-4), an immune-inhibitory site expressed on activated T cells. Ipilimumab is
      well tolerated as an outpatient infusion therapy. Multiple studies have confirmed
      significant antimelanoma activity. A randomized trial has documented a survival
      benefit when ipilimumab was compared to a gp-100 vaccine only arm. The unique
      mechanism of action of ipilimumab makes assessment of response by conventional
      criteria difficult. Benefit from ipilimumab can occur after what would be
      considered progression with World Health Oganization (WHO) or Response Evaluation
      Criteria in Solid Tumors (RECIST) criteria. New immune response criteria have
      been proposed. Therapeutic responses peak between 12 and 24 weeks, with slow
      responses continuing up to and beyond 12 months. The major drug- related adverse
      side effects (10%-15% grade 3 or above) are immune-related and consist most
      commonly of rash, colitis, hypophysitis, thyroiditis, and hepatitis. Colonic
      perforation can occur and patients with diarrhea have to be monitored carefully
      with strict adherence to treatment algorithms. Algorithms for the treatment of
      other adverse side effects have been developed. The treatment of immune-related
      side effects with immunosuppressive agents, such as corticosteroids, does not
      appear to impair antitumor response. With proper monitoring and management of
      side effects, ipilimumab is an extremely safe drug to administer. The benefits of
      ipilimumab will most certainly extend to other malignancies in the near future.

PMID- 21074059
TI  - Clinical development of the anti-CTLA-4 antibody tremelimumab.
AB  - Tremelimumab (formerly CP-675,206) is a fully human IgG2 monoclonal antibody
      tested in patients with cancer, of whom the majority have had metastatic
      melanoma. Clinical trials using tremelimumab demonstrate that this antibody can
      induce durable tumor regressions (up to 8 years at this time) in 7% to 10% of
      patients with metastatic melanoma. These tumor responses are mediated by the
      intratumoral infiltration of cytotoxic T lymphocytes (CTLs) as demonstrated in
      patient-derived tumor biopsies. Grade 3 or 4 toxicities in the range of 20% to
      25% are mainly inflammatory or autoimmune in nature, which are on-target effects
      after inhibiting CTLA-4-mediated self-tolerance. The lack of survival advantage
      in the early analysis of a phase III clinical trial comparing tremelimumab with
      standard chemotherapy for metastatic melanoma highlights the importance of
      gaining a better understanding of how this antibody modulates the human immune
      system and how to better select patients for this mode of therapy.

PMID- 21074060
TI  - Anti-CTLA-4 antibody adjuvant therapy in melanoma.
AB  - Thus far the development of adjuvant therapies in melanoma has suffered greatly
      from the lack of effective drugs in stage IV melanoma. Chemotherapy, cytokines,
      vaccines, and combinations of drugs have been used with minimal success. This has
      led to adjuvant therapies that are not used uniformly or widely because of the
      rather marginal benefits, as no consistent and clinically significant impact on
      survival has been demonstrated. A new development for interferon-based adjuvant
      therapy seems to be the observation that better effects are observed in patients
      with lower tumor load and in patients with an ulcerated primary melanoma. A
      benefit for patients with more advanced lymphnodal involvement is quite unsure,
      clearly requiring new drugs to be explored. A new era in the treatment of
      melanoma treatment has arrived with the anti-cytoxic T-lymphocyte antigen-4 (anti
      CTLA-4) monoclonal antibodies. The randomized trial in advanced metastatic
      melanoma demonstrated a clear benefit with prolongation of survival. The anti
      CTLA-4 monoclonal antibody ipilimumab has finally changed the landscape. It is
      therefore only logical that a worldwide adjuvant trial with ipilimumab versus
      placebo, the European Organization for Research and Treatment of Cancer (EORTC)
      18071, is ongoing in patients with lymph node metastases, and that another
      adjuvant trial with ipilimumab compared to high-dose interferon (HDI) is planned
      in the United States. The EORTC 18071 trial will reach full accrual in 2011 and
      thus results are expected in 2013 or 2014.

PMID- 21074061
TI  - Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications.
AB  - Available medical treatments have limited impact on the survival of patients with
      advanced cancer; therefore, new therapeutic strategies able to generate more
      effective host's immune responses against neoplastic cells are being actively
      pursued. Among these, a recent approach involves targeting of cytotoxic T
      lymphocyte antigen-4 (CTLA-4), a key immune checkpoint molecule, by monoclonal
      antibodies (mAbs). Ipilimumab and tremelimumab represent the prototypes of this
      new class of immunomodulating mAb and have been extensively tested in metastatic
      melanoma with highly promising results. The clinical activity observed in
      melanoma has served as a model to exploit the therapeutic potential of CTLA-4
      blockade in a variety of human malignancies. Along this line, early-phase trials
      with anti-CTLA-4 mAbs have been completed or are ongoing in tumors of different
      histotype. Results are demonstrating the feasibility, safety, and activity of
      these agents, thus suggesting a promising therapeutic role to be further
      investigated in phase II/III trials in a wide range of tumors. This review
      summarizes the main trials with ipilimumab and tremelimumab in tumors of
      different histotypes, excluding cutaneous melanoma, which is extensively
      described in other chapters of this issue of Seminars in Oncology.

PMID- 21074062
TI  - Brain metastasis in melanoma: clinical activity of CTLA-4 antibody therapy.
AB  - Melanoma metastasizes frequently to the brain, and brain metastases generally
      drive the prognosis of melanoma patients. Surgical and radiation therapy improve
      the outcome of selected melanoma patients with brain metastasis, while systemic
      treatment using cytotoxic agents still plays a limited role. Temozolomide and
      fotemustine are preferentially used in melanoma patients with brain metastases in
      the United States and in Europe, respectively, with modest clinical activity.
      However, the results obtained with either agent are still limited, and efforts
      are needed to improve the outcome of these patients who are generally excluded
      from clinical trials. Among therapeutic agents in development, antibodies that
      block the interaction of cytotoxic T-lymphocyte-associated antigen (CTLA-4) with
      its ligands B7.1 and B7.2 and thus enhance antitumor immune responses have shown
      clinical benefit in patients with metastatic melanoma, including durable control
      of brain metastases. This chapter reviews the current data and the rationale for
      ongoing and future trials of combination cytotoxic plus immunomodulatory therapy
      by US and Italian multicenter trial groups.

PMID- 21074064
TI  - Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma:
      identification of clinical and biological response patterns, immune-related
      adverse events, and their management.
AB  - Immune-modifying monoclonal antibodies may induce or enhance the natural immune
      response against tumor cells. The complex interaction between antigen-presenting
      cells and T lymphocytes as an immune response is strongly affected by anti-CD152
      (cytotoxic T-lymphocyte antigen-4, CTLA-4)-antibodies. However, specific CTLA-4
      antibodies can block the CTLA-4 receptor and thus induce an unrestrained T-cell
      activation. To this stage, treatment of patients with metastatic melanoma with
      the CTLA-4 antibodies ipilimumab and tremelimumab has only been investigated
      within clinical trials. The results of a phase III trial in patients with
      advanced disease treated with ipilimumab alone or in combination with a peptide
      vaccination (gp100) recently presented at the 2010 annual meeting of the Ameircan
      Society of Clinical Oncology (ASCO) made groundbreaking news as ipilimumab was
      demonstrated to be the first drug in melanoma treatment to show a significant
      prolongation of survival time. Patients undergoing treatment with CTLA-4
      antibodies may experience immune-related phenomena and adverse events (irAEs)
      that differ greatly from the well-known adverse events of cytotoxic drugs and
      which are due to the CTLA-4 antibodies' specific mode of action. This review
      gives a condensed overview on the mechanisms of action, an update on clinical
      data of the two CTLA-4 antibodies, ipilimumab and tremelimumab, and detailed
      recommendations for adverse event management strategies.

PMID- 21074063
TI  - Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a
      novel immunotherapy.
AB  - Cytotoxic T-lymphocyte-associated antigen (CTLA-4), also known as CD152, is a co
      inhibitory molecule that functions to regulate T-cell activation. Antibodies that
      block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune
      responses, including antitumor immunity. Two CTLA-4-blocking antibodies are
      presently under clinical investigation: ipilimumab and tremelimumab. CTLA-4
      blockade has shown promise in treatment of patients with metastatic melanoma,
      with a recently completed randomized, double-blind phase III trial demonstrating
      a benefit in overall survival (OS) in the treated population. However, this
      approach appears to benefit only a subset of patients. Understanding the
      mechanism(s) of action of CTLA-4 blockade and identifying prognostic immunologic
      correlates of clinical endpoints to monitor are presently areas of intense
      investigation. Several immunologic endpoints have been proposed to correlate with
      clinical activity. This review will focus on the endpoints of immune monitoring
      described in studies to date and discuss future areas of additional work needed.

PMID- 21074065
TI  - The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical
      indications.
AB  - The promising new class of immunomodulating antibodies directed against cytotoxic
      T-lymphocyte antigen-4 (CTLA-4) has been extensively tested in clinical trials
      and found to be active against cutaneous melanoma and other tumor histotypes.
      Inhibition of CTLA-4 characteristically induces well-identified side effects for
      which the definition "immune-related adverse events" (irAEs) has been proposed.
      IrAEs mainly include colitis/diarrhea, dermatitis, hepatitis, and
      endocrinopathies; uveitis, nephritis, and inflammatory myopathy also have been
      reported occasionally. These unique side effects are likely a direct result of
      breaking immune tolerance upon CTLA-4 blockade and are generally mild,
      reversible, and manageable, following specific treatment guidelines that include
      symptomatic therapies or systemic corticosteroids. However, patient-physician
      communication and early treatment are also emerging as critical issues to
      successfully manage irAEs, thus avoiding major complications. The major
      experience in identifying and managing CTLA-4 treatment-related side effects has
      derived from studies in melanoma patients; nevertheless, accumulating clinical
      experiences are clearly demonstrating that irAEs are class-specific events, and
      that they are fully overlapping in patients with tumors of different histotypes.
      This review provides an overview of current safety data on CTLA-4 antagonists and
      of available strategies to optimize their clinical use in cancer patients.

PMID- 21074066
TI  - Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies.
AB  - Monoclonal antibodies (mAbs) provide a pharmacological platform to block or
      activate the function of surface receptors. The immune system has evolved
      receptor-ligand pairs that repress or empower the cellular immune response,
      which, if tampered with, unleash more potent cellular immunity against tumor
      antigens. Agonist antibodies directed against CD137 (4-1BB) on the surface of
      antigen-primed T lymphocytes increase tumor immunity that is curative against
      some transplantable murine tumors. A fully human IgG4 anti-CD137 antibody is
      under development with signs of clinical activity and cases of severe liver
      toxicity that seem to be on-target and dose-dependent effects. Programmed death-1
      (PD1) is a surface molecule delivering inhibitory signals important to maintain T
      cell functional silence against their cognate antigens. Interference with PD1 or
      its ligand PD-L1 (B7-H1) increases antitumor immunity. As a result anti-PD1 and
      anti-PD-L1 human mAbs are under clinical development. Phase I trials with anti
      PD1 mAb have yielded encouraging results with durable objective responses and a
      reasonable safety profile. As new class of drugs in cancer therapy,
      immunostimulatory mAbs have resulted in redefinition of tumor response criteria
      and rethinking of the rationale for combining these among each other and with
      other strategies.

PMID- 21074067
TI  - Biology and clinical applications of CD40 in cancer treatment.
AB  - CD40 is a costimulatory molecule widely expressed by immune cells and by
      neoplastic cells of different histotypes. Engagement of surface CD40 mediates
      different effects depending on cell type and microenvironment. In particular,
      CD40 expression on immune cells regulates humoral and cellular immunity, while it
      has apoptotic and antiproliferative activity on selected neoplastic cells. Thus,
      CD40 targeting may indirectly affect tumor growth through the activation of
      immune cells and/or directly by mediating cytotoxic effects on neoplastic cells.
      Preliminary findings emerging from clinical trials indicate that antibodies to
      CD40 can induce immune modulation and clinical responses in cancer patients.

PMID- 21074069
TI  - Development of ipilimumab: contribution to a new paradigm for cancer
      immunotherapy.
AB  - Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative
      regulator of T-cell activity led to development of the fully human, monoclonal
      antibody ipilimumab to block CTLA-4 and potentiate antitumor T-cell responses.
      Animal studies first provided insight into the ability of an anti-CTLA-4 antibody
      to cause tumor regression, particularly in combination regimens. Early clinical
      studies defined ipilimumab pharmacokinetics and possibilities for combinability.
      Phase II trials of ipilimumab in advanced melanoma showed objective responses,
      but a greater number of patients had disease stabilization. In a phase III trial,
      ipilimumab was the first agent to demonstrate an improvement in overall survival
      in patients with previously treated, advanced melanoma. The adverse event profile
      associated with ipilimumab was primarily immune-related. Adverse events can be
      severe and life-threatening, but most were reversible using treatment guidelines.
      Ipilimumab monotherapy exhibits conventional and new patterns of activity in
      advanced melanoma, with a delayed separation of Kaplan-Meier survival curves. The
      observation of some new response patterns with ipilimumab, which are not captured
      by standard response criteria, led to novel criteria for the evaluation of
      immunotherapy in solid tumors. Overall, lessons from the development of
      ipilimumab contributed to a new clinical paradigm for cancer immunotherapy
      evolved by the Cancer Immunotherapy Consortium.

PMID- 21074070
TI  - [Diagnosis and management of type 2 diabetes].
AB  - In 2010, the American Diabetes Association included glycosylated hemoglobin
      (HbA1c) as a criterion for the diagnosis of diabetes with a cut-off point of >=
      6.5%. However, there may be a substantial percentage of false negative results.
      Other scientific societies have accepted this approach but with slight
      differences. HbA1c complements, but does not substitute, basal glycemia as a
      screening and diagnostic test or the 2-hour oral glucose tolerance test. HbA1c
      should not be used for the diagnosis of gestational diabetes. Interpretation of
      HbA1c is limited in persons with anemia and hemoglobinopathies. Therefore, in
      addition to its sensitivity and specificity, its costs and the epidemiological
      situation should also be evaluated. An important question is whether almost
      normal HbA1c levels are safe in patients with type 2 diabetes. The results of the
      ACCORD, ADVANCE and VADT trials are contradictory and have aroused considerable
      controversy. However, the extensions of the UKPDS and STENO-2 studies have shown
      the benefits of good glycemic control in the long term. As a general rule, a
      target of HbA1c < 7% seems appropriate. In patients at low risk of hypoglycemic
      episodes, short disease duration and young persons, HbA1c < 6.5% can be
      considered. In patients with frequent hypoglycemic episodes, the elderly and
      persons with short life expectancy, values of more than 7% are acceptable. This
      target should be achieved through individualized, early, intensive and safe
      treatment, without risk of hypoglycemia, and should be integrated in an overall
      program of cardiovascular risk prevention.

PMID- 21074068
TI  - Signaling through OX40 enhances antitumor immunity.
AB  - The existence of tumor-specific T cells, as well as their ability to be primed in
      cancer patients, confirms that the immune response can be deployed to combat
      cancer. However, there are obstacles that must be overcome to convert the
      ineffective immune response commonly found in the tumor environment to one that
      leads to sustained destruction of tumor. Members of the tumor necrosis factor
      (TNF) superfamily direct diverse immune functions. OX40 and its ligand, OX40L,
      are key TNF members that augment T-cell expansion, cytokine production, and
      survival. OX40 signaling also controls regulatory T-cell differentiation and
      suppressive function. Studies over the past decade have demonstrated that OX40
      agonists enhance antitumor immunity in preclinical models using immunogenic
      tumors; however, treatment of poorly immunogenic tumors has been less successful.
      Combining strategies that prime tumor-specific T cells together with OX40
      signaling could generate and maintain a therapeutic antitumor immune response.

PMID- 21074071
TI  - [Current clinical practice guidelines in type 2 diabetes: how should they be
      applied in primary care?].
AB  - Clinical practice guidelines should be drawn up with systematic methodology based
      on the best available evidence. Recommendations should be based on evaluation of
      the overall quality of the evidence and grading of the strength of
      recommendations. Consensus documents combine a review of the evidence with expert
      opinion in an attempt to reach some agreement in areas of uncertainty due to the
      lack of conclusive proof. The debate aroused by new treatments stimulates the
      production of documents advocating their use even when there are few long-term
      studies on their safety and efficacy. There are several methodologically rigorous
      international guidelines on diabetes (NGC, NICE, SIGN, CAD, ADA). The most recent
      debate has centered on the ADA-EASD treatment algorithm. In Spain, the production
      of clinical practice guidelines with analysis of the evidence and grading of
      recommendations remains scarce, although the most recent published guidelines
      show greater rigor. More common is the drafting of consensus documents by
      scientific societies with the aim of combining external evidence with experience
      and reflection. In Spain there are also organisms (such as GuiaSalud or Fisterra)
      that facilitate free access to guidelines drawn up by Spanish groups.

PMID- 21074072
TI  - [Diabetes mellitus and cardiovascular risk. Is integrated therapy of type 2
      diabetes and cardiovascular risk factors necessary?].
AB  - Cardiovascular disease (CVD) is the first cause of death in the Spanish
      population among both diabetics and non-diabetics. In diabetes, CVD is between 2
      and 4 times more frequent, earlier and more aggressive. With current measures,
      approximately 50% of CVD can be prevented. The risk factors for CVD in diabetes
      are hypertension, dyslipidemia, smoking, obesity and sedentariness. More than 80%
      of patient with type 2 diabetes have hypertension and dyslipidemia and
      approximately 15% continue to smoke. However, all these factors are controlled in
      at least 10%. Although dyslipidemia is the most influential and least treated
      factor, the greatest benefit for CVD prevention is obtained with integrated
      intervention on all risk factors, reducing blood pressure to below 140/80 mmHg,
      low-density lipoprotein cholesterol (LDL-c) to below 100 mg/dl, encouraging
      smoking cessation, regular physical activity and maintaining a healthy weight
      (BMI < 25 kg/m2). In secondary prevention or persons with microvascular disease,
      the targets may be stricter (blood pressure 130/80 mmHg and LDL-c 80 mg/dl). Drug
      treatment should always include an angiotensin converting-enzyme inhibitor or an
      angiotensin II receptor antagonist and a statin. Aspirin should be reserved for
      patients in secondary prevention or with very high CV risk. Consequently,
      interventions should be prioritized according to the foreseeable risk for each
      patient, which can be estimated through the SCORE scale or other scales such as
      Regicor or UKPDS, with a SCORE > 5% indicating high risk. These high-risk
      patients should receive personalized care.

PMID- 21074073
TI  - [Panorama of currently available treatments for patients with type 2 diabetes.
      The ADA/EASD treatment algorithm. Safety and tolerability].
AB  - Type 2 diabetes is defined by chronic hyperglycemia due to at least two
      pathogenic alterations: resistance to the action of peripheral insulin and
      insufficient pancreatic insulin secretion. The pharmacological treatment of
      hyperglycemia in type 2 diabetes should be individualized. The choice of specific
      oral drug (or combination of drugs) is based on the drug's physiological
      mechanism, the general recommendations of the clinical practice guidelines,
      systematic reviews and analysis of data from clinical trials and observational
      studies. In general terms, clinical practice guidelines recommend starting with
      lifestyle modifications together with metformin, either from the outset or at 3
      months; the combination should be individualized depending on the patient's
      profile. Therapy may be intensified every 3-6 months until targets (HbA1c 6.5
      7.5%) have been reached. To chose the second drug, both its efficacy (mechanism
      of action) and side effects (hypoglycemic episodes, effect on weight, intestinal
      effects, edema/cardiac insufficiency and renal or liver insufficiency) should be
      considered. The controversy on the safety of oral drugs and insulin is constantly
      reviewed. The cardiovascular safety of intensive hyperglycemia treatment in
      patients with type 2 diabetes, particularly with certain agents, is an open
      debate. Finally, the association between insulin and cancer has aroused huge
      interest but the clinical significance of this association remains uncertain and
      further analyses are required to clarify this issue.

PMID- 21074074
TI  - [Update on the latest family of oral drugs marketed for the treatment of type 2
      diabetes: DPP-4 inhibitors. Contributions with respect to other families of oral
      antidiabetic agents].
AB  - The recent introduction of new drugs in the therapeutic arsenal for the
      management of hyperglycemia in type 2 diabetes has opened up new perspectives and
      raised hope for improved metabolic control in these patients. DPP-4 inhibitors
      are a family of drugs whose action is mediated by the incretin hormones, in
      particular GLP-1. This hormone is involved in the control of glucose homeostasis,
      as it stimulates insulin secretion in response to food intake and halts glucagon
      production. This effect, which is altered in patients with type 2 diabetes, can
      be improved by administering this group of drugs. The available evidence suggests
      that the efficacy, tolerability, safety, low drop-out rate and limited effects on
      weight, together with the low risk of hypoglycemic episodes, could place this
      group of drugs high on the treatment list in patients with type 2 diabetes.
      Incretin therapy provides an alternative to currently available glucose-lowering
      drugs for type 2 diabetes with good efficacy and a favorable profile on weight.
      In the studies performed to date, DPP-4 inhibitors seem safe. However, these
      agents must continue to be evaluated in long-term studies performed in clinical
      practice to ensure their effectiveness and safety profile, as well as to
      determine their precise role among all the currently available options in the
      treatment of type 2 diabetes.

PMID- 21074075
TI  - [Importance of patient involvement in disease self-management: the expert
      patient. Role of new technologies to support patient autonomy].
AB  - Because of population aging in our geographical and social setting and progress
      in preventing premature death, there is an ever-increasing prevalence of chronic
      diseases, in this case diabetes. In our environment, the dietary changes and
      sedentariness that have led to the spectacular rise in obesity have increased the
      prevalence of diabetes. Our health system is reasonably well prepared to manage
      acute disease but neither health professionals nor referral circuits -nor
      probably patients- are prepared for the new scenario. Consequently, we should
      prepare ourselves for the management of chronic disease, encourage patient
      participation in decision-making and promote a new, less paternalistic, paradigm
      of the doctor-patient relationship. The experiences initiated by the University
      of Stanford, or in Spain by the National Patients' Forum, could serve as models.
      In the next few years, the figure of the expert patient will undoubtedly be
      highly useful. In general, physicians and patients place a great deal of faith in
      the contribution of new treatments and technologies to the relief or management
      of disease. To deny this in the XXI century would be ridiculous, but all the
      possibilities of these treatments and technologies only show positive results in
      suitably educated patients. This is a task that should never be forgotten.

PMID- 21074076
TI  - Concussion in sports. Foreword.

PMID- 21074077
TI  - Concussion results in deficits in neurocognitive functioning. Preface.

PMID- 21074078
TI  - The epidemiology of sport-related concussion.
AB  - Concussions and head injuries may never be completely eliminated from sports.
      However, with better data comes an improved understanding of the types of actions
      and activities that typically result in concussions. With this knowledge can come
      improved techniques and rule changes to minimize the rate and severity of
      concussions in sports. This article identifies the factors that affect concussion
      rate.

PMID- 21074080
TI  - The molecular pathophysiology of concussive brain injury.
AB  - Concussion or mild traumatic brain injury (mTBI) is a condition that affects
      hundreds of thousands of patients worldwide. Understanding the pathophysiology of
      this disorder can help manage its acute and chronic repercussions. Immediately
      following mTBI, there are several metabolic, hemodynamic, structural, and
      electric changes that alter normal cerebral function. These alterations can
      increase the brain's vulnerability to repeat injury and long-term disability.
      This review evaluates current studies from the bench to the bedside of mTBI.
      Acute and chronic effects of concussion are measured in both animal and clinical
      studies. Also, the effect of repeat concussions is analyzed. Concussion-induced
      pathophysiology with regards to glucose metabolism changes, mitochondrial
      dysfunction, axonal injury, and structural damage are evaluated. Translational
      studies such as functional magnetic resonance imaging, magnetic resonance
      spectroscopy and diffusion tensor imaging prove to be effective clinical tools
      for both prognostic and treatment parameters. Understanding the neurobiology of
      concussion will lead to development and validation of physiological biomarkers of
      this common injury. These biomarkers (eg, laboratory tests, imaging,
      electrophysiology) will then allow for improved detection, better functional
      assessment and evidence-based return to play recommendations.

PMID- 21074079
TI  - Biomechanics of concussion.
AB  - The rising awareness of the long-term health problems associated with concussions
      re-emphasizes the need for understanding the mechanical etiology of concussions.
      This article reviews past studies defining the common mechanisms for mild
      traumatic brain injury and summarizes efforts to convert the external input to
      the head (force, acceleration, and velocity) into estimates of motions and
      deformations of the brain that occur during mild traumatic brain injury. Studies
      of how these mechanical conditions contribute to the cellular mechanisms of
      damage in mild traumatic brain injury are reviewed. Finally, future directions
      for improving understanding concussion biomechanics are discussed.

PMID- 21074081
TI  - The acute symptoms of sport-related concussion: diagnosis and on-field
      management.
AB  - Sport-related concussion is a common injury that occurs in a variety of sports.
      In recent years, more attention has been focused on the importance of this injury
      as well as the long-term complications of unrecognized, repetitive, and/or severe
      injury. The acute presentation of concussion as well as the diagnosis of
      concussion is often straightforward and obvious, but it can also be subtle and
      difficult to discern. Most injuries are short lived with complete recovery within
      a couple of weeks, with a small minority taking several months to resolve.
      Unfortunately, it is difficult to predict which injuries will linger. This
      article discusses the on-field presentation, diagnosis, and management of sport
      related concussion. It is important to have a concussion protocol for high-risk
      sports, including a preseason and postinjury assessment, and an individualized
      yet comprehensive approach that includes evaluating symptoms, and a neurologic
      examination that includes cognitive function and balance testing. A multifaceted
      approach to the evaluation and diagnosis of concussion is endorsed for the
      optimal management of this injury.

PMID- 21074082
TI  - Subacute symptoms of sports-related concussion: outpatient management and return
      to play.
AB  - Most concussion symptoms resolve within the first week after injury. Athletes
      with persistent symptoms may manifest subtle behavioral and cognitive changes.
      The astute clinician uses various information to determine when these symptoms
      have cleared before allowing the athlete to return to athletic competition.

PMID- 21074083
TI  - Neuropsychological assessment of sport-related concussion.
AB  - Assessment of concussion can be challenging for medical practitioners given the
      different factors associated with each individual injury. The use of
      neuropsychological testing provides an objective method in the evaluation and
      management of concussion. Over the last 20 years it has become increasingly
      useful in the realm of sports concussion and has been deemed a cornerstone of
      concussion management by the Concussion in Sport group at the International
      Symposia on Concussion in Sport. Neuropsychological assessment has evolved to
      using computer-based neurocognitive testing, which has become increasingly common
      over the last decade, especially in organized sports. Neuropsychological
      assessment has also proven to be effective in the detection of differences based
      on several individual factors, including age, gender, and history of prior
      concussion. Despite its documented value, neuropsychological assessment should be
      one of several tools used as part of the concussion assessment/management
      process.

PMID- 21074084
TI  - Balance assessment in the management of sport-related concussion.
AB  - Although neuropsychological testing has proven to be a valuable tool in
      concussion management, it is most useful when administered as part of a
      comprehensive assessment battery that includes grading of symptoms and clinical
      balance tests. A thorough sideline and clinical examination by the certified
      athletic trainer and team physician is considered an important first step in the
      management of concussion. The evaluation should be conducted in a systematic
      manner, whether on the field or in the clinical setting. The evaluation should
      include obtaining a history for specific details about the injury (eg, mechanism,
      symptomatology, concussion history), followed by assessing neurocognitive
      function and balance, which is the focus of this article. The objective measures
      from balance testing can provide clinicians with an additional piece of the
      concussion puzzle, remove some of the guesswork in uncovering less obvious
      symptoms, and assist in determining readiness to return safely to participation.

PMID- 21074085
TI  - The role of neuroimaging in sport-related concussion.
AB  - This article describes some of the newer techniques that are being used in the
      clinical assessment of patients following mild to moderate TBI, addresses their
      use in the acute setting, and explores their potential role in long-term follow
      up. Also addressed are the challenges faced before some of these newer techniques
      can be incorporated into routine clinical management. Large studies are needed
      with a special emphasis on the effects of repeated head trauma in the young
      athlete. This is especially relevant where conventional imaging does not
      demonstrate a macroscopic abnormality. The emphasis has to shift from identifying
      structural abnormalities on imaging studies to understanding the functional
      changes in the brain that may explain the long-term neuropsychological effects of
      concussion and mTBI.

PMID- 21074087
TI  - The female athlete: the role of gender in the assessment and management of sport
      related concussion.
AB  - Concussions remain a serious public health concern, with approximately 1.6
      million to 3 million sport and recreational traumatic and brain injuries
      occurring every year in the United States. Most research on concussions has been
      conducted on male athletes, specifically, football players. However, female sport
      participation has steadily increased over the past decade. Recent studies suggest
      that the incidence of and recovery from sport-related concussion varies between
      male and female athletes, with women having a higher risk of sustaining a
      concussion and taking a longer time to recover than men. As a result, this
      article addresses the role of gender in the assessment and management of sport
      related concussion.

PMID- 21074086
TI  - Medical therapies for concussion.
AB  - Clinicians who manage sport-related concussions have excellent guidelines by
      which most injuries can be managed. Because sport-related concussions typically
      resolve within a short time frame, most can be managed with physical and
      cognitive rest alone. However, clinicians who specialize in the assessment and
      management of this diagnosis encounter patients with prolonged recovery courses,
      persistent symptoms, and significant deficits in cognitive functioning. These
      patients require more involved therapy, which may include additional education,
      academic accommodations, physical therapy, cognitive rehabilitation, and
      medication. This article reviews the main medical therapies for the management of
      concussive brain injury.

PMID- 21074088
TI  - The pediatric athlete: younger athletes with sport-related concussion.
AB  - Although much of the lay media attention surrounding sport-related concussion
      (SRC) focuses on professional athletes, SRC is a common injury in pediatric
      sports. The anatomy, biomechanics, and response to injury of the developing
      pediatric brain differ from those of the adult. Similarly, the neurocognitive
      abilities of the child are developing more rapidly than in an adult. The effects
      of concussive brain injury on the life of a child are different from those of an
      adult. This article focuses on the aspects of SRC that are specific to the
      younger athletes.

PMID- 21074089
TI  - Helmets and mouth guards: the role of personal equipment in preventing sport
      related concussions.
AB  - Millions of athletes in the United States experience concussions annually.
      Although helmets and mouth guards have decreased the risk of catastrophic head
      injuries, their protective effects on concussions are less clear. This article
      evaluates the current literature on the effect of equipment on concussions.
      Understanding the role that these equipment play in preventing concussions is
      complicated by many factors, such as selection bias in nonrandomized studies,
      variations in playing style, and risk compensation in sports with mandatory
      protective equipment. Improving coach and player education about proper
      concussion management, encouraging neck-strengthening exercises, and minimizing
      high-risk impacts may reduce concussions in sports.

PMID- 21074090
TI  - Long-term neurocognitive dysfunction in sports: what is the evidence?
AB  - Although the immediate neurocognitive effects of sports-related concussion are
      well known, less is known about the intermediate or long-term effects of sports
      related concussions. A sample of selected studies of high-school and collegiate
      athletes is reviewed and the intermediate effects of concussive injuries are
      discussed, because no long-term empiric data are available with these
      populations. The evidence for intermediate neurocognitive effects is mixed and
      not convincing at present in these groups of athletes. Selected studies of
      professional boxers and American professional football players are also reviewed,
      and the available data regarding long-term neurocognitive and neuropathologic
      effects are assessed. The evidence for long-term adverse neurocognitive effects
      in professional boxers is compelling. Suggestions for future research on relevant
      biopsychosocial variables affecting response to concussive injury are presented.

PMID- 21074092
TI  - When to consider retiring an athlete after sports-related concussion.
AB  - The pathophysiology of concussion may lead to a variety of both short- and long
      term effects, which may lead to a decision to retire from contact sports. These
      effects follow a recognizable progression and may cause an athlete to opt out of
      play at any point along this progression. To elucidate the effect of concussion
      or mild traumatic brain injury and weigh in on a decision to retire, the treating
      physician needs to take into account the history, neurologic examination, brain
      imaging, and neuropsychological testing. In addition, myriad social factors
      surrounding play must be taken into consideration.

PMID- 21074091
TI  - Chronic traumatic encephalopathy: a potential late effect of sport-related
      concussive and subconcussive head trauma.
AB  - Chronic traumatic encephalopathy (CTE) is a form of neurodegeneration believed to
      result from repeated head injuries. Originally termed dementia pugilistica
      because of its association with boxing, the neuropathology of CTE was first
      described by Corsellis in 1973 in a case series of 15 retired boxers. CTE has
      recently been found to occur after other causes of repeated head trauma,
      suggesting that any repeated blows to the head, such as those that occur in
      American football, hockey, soccer, professional wrestling, and physical abuse,
      can also lead to neurodegenerative changes. These changes often include cerebral
      atrophy, cavum septi pellucidi with fenestrations, shrinkage of the mammillary
      bodies, dense tau immunoreactive inclusions (neurofibrillary tangles, glial
      tangles, and neuropil neurites), and, in some cases, a TDP-43 proteinopathy. In
      association with these pathologic changes, disordered memory and executive
      functioning, behavioral and personality disturbances (eg, apathy, depression,
      irritability, impulsiveness, suicidality), parkinsonism, and, occasionally, motor
      neuron disease are seen in affected individuals. No formal clinical or pathologic
      diagnostic criteria for CTE currently exist, but the distinctive neuropathologic
      profile of the disorder lends promise for future research into its prevention,
      diagnosis, and treatment.

PMID- 21074093
TI  - Future advances and areas of future focus in the treatment of sport-related
      concussion.
AB  - The occurrence and management of sports concussion provokes more debate and
      concern than virtually all other sports injuries combined. In the past 3 decades,
      clinicians have gone from mostly anecdotal strategies to an international
      consensus-based approach and the early evolution of evidence-based practice.
      There is increasing engagement by mainstream neuroscientists in this field, which
      had previously been dominated by sports team physicians. However, the interchange
      has largely taken place in the media rather than through scientific journals.
      Legislators have proposed regulatory measures that restrict medical management of
      concussion in ways that apply to no other medical condition. This paper examines
      some of the key areas that are likely to be the focus of research in the next few
      years.

PMID- 21074094
TI  - [The value of "Articles in Press"].

PMID- 21074095
TI  - [Clinical features of ocular toxoplasmosis in an inmigrant population in the
      Barcelona area: Study of 22 patients].
AB  - PURPOSE: To report the epidemiological, clinical and prognostic features of
      ocular toxoplasmosis in an immigrant population in the Barcelona area. METHODS: A
      retrospective non-comparative observational study was conducted on a case series
      of 22 immigrant patients diagnosed with ocular toxoplasmosis by ophthalmoscopic
      and serological findings. Demographic, clinical and laboratory data were analysed
      under baseline conditions. The minimum follow-up was 6 months. RESULTS: Bilateral
      involvement was observed in five of the 22 patients (22.7%), a total of 27 eyes
      being affected by active lesions and old scars. Atypical presentations, including
      multiple or large necrotizing lesions, were observed in 5 eyes (25%). In 15 eyes
      (75%) the retinal lesions were associated with intraocular inflammation.
      Vitreoretinal complications were observed in eight eyes (29.6%), with 22.7% of
      them requiring vitreous surgery. CONCLUSIONS: In immigrant patients from our area
      in Barcelona, ocular toxoplasmosis has specific clinical and prognostic features,
      including high rates of atypical presentations, frequent intraocular
      inflammation, and vitreoretinal complications, requiring surgery in most of the
      cases.

PMID- 21074096
TI  - [Effect of treatment in loss of retinal nerve fibre layer in multiple sclerosis
      patients].
AB  - OBJECTIVE: To evaluate the effect of pathogenic treatments in the reduction of
      the retinal nerve fibre layer (RNFL) in patients with Multiple Sclerosis (MS) by
      means of ocular imaging technologies. MATERIAL AND METHODS: A total 155 eyes of
      79 patients with MS were enrolled in this study. All patients underwent a
      complete ophthalmic examination including best corrected visual acuity using
      Snellen chart, colour vision using Ishihara pseudoisochromatic plates, visual
      field examination, optical coherence tomography (OCT), scanning laser polarimetry
      (GDx) and visual evoked potentials. The patients were re-evaluated after a one
      year period and changes were assessed in order to detect differences between
      treatments using the Anova statistical test. The patients were divided into four
      groups: 1) Patients without treatment, 2) Patients treated with interferon beta
      1a, 3) Subjects who received interferon beta-1b, 4) Patients treated using
      glatiramer acetate. RESULTS: There were no statistically significant differences
      between patients with or without treatment and between the four groups (P>0.05, t
      test), but functional and structural parameters showed greater loss in RNFL
      thickness in non-treated patients. Temporal quadrant RNFL thickness measured by
      OCT was the parameter with the highest variation (reduction of 4.97MUm in
      patients without treatment vs 1.08MUm in treated patients). CONCLUSIONS: MS
      pathogenic treatment may be a protective factor in the RNFL loss that is
      associated to the disease progression. More studies are needed.

PMID- 21074097
TI  - [Dermoid cyst in childhood, diagnosed as ptosis].
AB  - CLINICAL CASE: A four year-old boy, diagnosed of palpebral ptosis since he was 2
      by his paediatrician. At the initial ophthalmological revies he had asymmetrical
      upper eyelids. In the follow-up a mild ocular hypotrophy appeared in his left eye
      and an increasing astigmatism, which made us suspect an orbital disease. The MRI
      confirmed a mass, compatible with a dermoid cyst. CONCLUSION: Due to the slow
      growth of these tumours, it is only with clinical follow-up and the aid of
      imaging techniques that we may achieve the diagnosis and offer a definitive
      treatment with surgical extirpation.

PMID- 21074098
TI  - [Blindness in the work by Jorge Luis Borges: "Seven nights: Blindness"].

PMID- 21074100
TI  - Towards clarity: what does "inappropriate imaging" really mean?

PMID- 21074099
TI  - [Pretended and emerging but unfallen tears Cornelis Troost (Amsterdam,
      Netherlands; 1696-1750)].

PMID- 21074101
TI  - Case of the month #166: carcinoid heart disease. Carcinoid syndrome.

PMID- 21074103
TI  - Canada, the olympics, and radiology.

PMID- 21074102
TI  - Case of the month #167: intrauterine contraceptive device migration to the
      descending sigmoid colon after uterine perforation.

PMID- 21074104
TI  - An age-period-cohort analysis of gastric cancer mortality from 1950 to 2007 in
      Europe.
AB  - PURPOSE: To analyze the components of the favorable trends in gastric cancer in
      Europe. METHODS: From official certified deaths from gastric cancer and
      population estimates for 42 countries of the European geographical region, during
      the period 1950 to 2007, age-standardized death rates (World Standard Population)
      were computed, and an age-period-cohort analysis was performed. RESULTS: Central
      and Northern countries with lower rates in the 2005 to 2007 period, such as
      France (5.28 and 1.93/100,000, men and women respectively) and Sweden (4.49 and
      2.21/100,000), had descending period and cohort effects that decreased steeply
      from the earliest cohorts until those born in the 1940s, to then stabilize.
      Former nonmarket economy countries had mortality rates greater than 20/100,000
      men and 10/100,000 women, and displayed a later start in the cohort effect fall,
      which continued in the younger cohorts. Mortality remained high in some countries
      of Southern and Eastern Europe. CONCLUSIONS: The decrease in gastric cancer
      mortality was observed in both cohort and period effects but was larger in the
      cohorts, suggesting that the downward trends are likely to persist in countries
      with higher rates. In a few Western countries with very low rates an asymptote
      appears to have been reached for cohorts born after the 1940s, particularly in
      women.

PMID- 21074105
TI  - Age-specific spatio-temporal patterns of female breast cancer mortality in Spain
      (1975-2005).
AB  - PURPOSE: In recent decades, a decline in breast cancer mortality has been
      observed across Europe, and also in Spain. Our objective is to assess the spatio
      temporal pattern during the period 1975-2005 by specific age groups (<45, 45-64,
      >=65) in the Spanish provinces. METHODS: For each age group, a spatio-temporal P
      spline model with a B-spline basis is used to smooth the mortality risks.
      Smoothing is carried out in three dimensions: longitude, latitude, and time,
      allowing for a different time evolution of both spatial components. The age
      specific decline is calculated as the maximum of the estimated curve in each
      province. A confidence band for each curve is also provided. RESULTS: For the
      first age group (<45), the decline in the different provinces is observed between
      1986 and 1991. For women aged between 45 to 64 years, the change occurs between
      1990 and 1993. For the third age group (>=65), change points range from 1992 to
      2000, unlike Malaga and Cadiz where the change has not been observed in the
      studied period. Northern and some Mediterranean provinces are the areas with
      higher mortality risks for all the age groups. CONCLUSIONS: A different behavior
      for breast cancer mortality risks is observed for different provinces among the
      age specific groups. The decline of mortality is delayed for the oldest age
      group. Province differences in the implementation of screening programs could
      explain some of the observed differences.

PMID- 21074106
TI  - Glaucoma medications and mortality: a retrospective cohort study.
AB  - PURPOSE: This study presents a retrospective, cohort analysis to estimate the 4
      year rate of all-cause risk-adjusted mortality for veterans who were dispensed
      glaucoma medications. The main outcome measures was hazard of death according to
      glaucoma medication exposure. METHODS: Beneficiaries 40 years and older enrolled
      in Veterans Health Administration (VHA) with International Disease Classification
      diagnoses of glaucoma. VHA clinical and pharmacy data sets were linked with a
      national VHA mortality registry. Patients were identified with a primary
      diagnosis of glaucoma were then put into one of two groups, glaucoma medication
      exposure or nonexposure medication group. Four-year survival analysis using the
      Cox proportional hazard method was adjusted for comorbidities using pertinent
      demographic characteristics and hierarchical condition categories from the
      Centers for Medicare and Medicaid Services. RESULTS: Of 214,971 beneficiaries
      with glaucoma or suspected glaucoma, 25,148 (11.7%) died during the study period.
      Compared to unexposed patients with glaucoma, the use of any class of glaucoma
      medication was associated with a statistically significant 7% reduced hazard of
      death (adjusted hazard ratio, 0.93; 95% confidence interval: 0.90-0.95). Reduced
      risk of death was found for multiple topical medication use, but not individual
      glaucoma agents. CONCLUSIONS: The seemingly inexplicable protective effect of
      glaucoma agents on all-cause mortality may best be explained by unmeasured
      confounding variables involved in the clinical decision of whether or not to
      treat patients with limited life expectancy for glaucoma.

PMID- 21074107
TI  - Investigation of disparities in geographic accessibility to emergency stroke and
      myocardial infarction care in East tennessee using geographic information systems
      and network analysis.
AB  - PURPOSE: Stroke and myocardial infarction (MI) require timely geographic
      accessibility to emergency care. Historically, studies used straight line
      distances as measures of geographic accessibility. Recently, travel time has been
      recognized as a better indicator of accessibility because travel impedances can
      be considered. This study used finer grained transportation data and network
      analysis to investigate neighborhood disparities in travel time to emergency
      stroke and MI care. METHODS: Travel times to stroke and cardiac centers were
      computed using network analysis, while considering distance, speed limit, road
      connectivity, and turn impedances. Neighborhoods within 30, 60, or 90 minutes
      travel were identified. Travel time by air ambulance was calculated and adjusted
      for flying speed and some delays. RESULTS: Approximately 8% and 15% of the study
      population did not have timely geographic accessibility to emergency stroke and
      MI care, respectively. Populations with poor access were located in rural areas.
      The entire study population had timely access by air ambulance. CONCLUSIONS: This
      study identified disparities in geographic accessibility to emergency stroke and
      MI care in East Tennessee. Use of air ambulance or telemedicine could play a
      vital role in addressing these disparities. This information is important for
      evidence-based health planning and resource allocation.

PMID- 21074108
TI  - Application of a new method for linking anonymous survey data in a population of
      soldiers returning from Iraq.
AB  - PURPOSE: This study provides a unique application of a procedure to link
      anonymous survey records as a means to assess mental health problems among
      soldiers after return from deployment to Iraq. The research purpose is to
      validate the use of a linkage method on anonymous survey data for longitudinal
      analysis. METHODS: This research analyzes surveys completed by soldiers at three
      (N = 4,903), six (N = 3,110), and 12 (N = 2,544) months post-Operation Iraqi
      Freedom (OIF) deployment. To protect anonymity while also allowing for
      longitudinal analysis, the survey includes four self-generated codes for matching
      the surveys from individual soldiers. The surveys were linked using Link Plus
      (Centers for Disease Control and Prevention, Atlanta, GA). Three matched groups
      (3-6 months, 6-12 months, and 3-12 months) were created, matching on the
      anonymous codes and demographic variables. An internal validation of the linkage
      results was performed and selection bias was assessed. RESULTS: The matched
      records showed very high agreement in variables not included in the matching
      procedure and were similar to the unmatched records with regard to demographics
      and post-traumatic stress disorder (PTSD) prevalence. CONCLUSIONS: The use of
      self-generated codes protects anonymity while the method utilized and validated
      in this paper allows for longitudinal data analysis. The results support an
      absence of any notable selection bias.

PMID- 21074109
TI  - Stability of combat exposure recall in Operation Iraqi Freedom veterans.
AB  - PURPOSE: This study evaluates changes in recall of combat exposures over the
      first year after return from deployment. The research purpose is to assess
      whether recall of combat exposures is consistent at different time points; if
      not, what demographic and/or PTSD symptom risk factors exist for any directional
      instability. METHODS: Surveys completed by soldiers at 3, 6, and 12 months post
      Operation Iraqi Freedom (OIF) deployment were linked for longitudinal analysis in
      a previous study in which three matched datasets were created: 3-6 months (N =
      768), 6-12 months (N = 341), and 3-12 months (N = 445). Post-traumatic stress
      disorder (PTSD) was assessed by using the National Center for PTSD Checklist. The
      reliability of recall for 36 combat exposures was quantified. The effects of
      demographics and change in PTSD score on combat exposure recall were assessed.
      RESULTS: The results showed an average of 80% to 90% agreement in combat exposure
      reporting between the time points. Every one-unit change in PTSD score was
      associated with a 0.1- to 0.5-unit change in recall of combat exposures over
      time. CONCLUSIONS: This study demonstrates that over the first year after return
      from deployment to Iraq, recall of combat experiences remained stable, and PTSD
      was slightly associated with increased reporting of combat exposures over time.

PMID- 21074110
TI  - Combined measure of pro- and anti-oxidant exposures in relation to prostate
      cancer and colorectal adenoma risk: an update.
AB  - PURPOSE: We previously proposed an oxidative balance score (OBS) and illustrated
      its practical application by using data from previously completed case-control
      studies of two neoplasms - sporadic colorectal adenoma and prostate cancer. In
      the present study we extend our analysis by substituting questionnaire-based
      measures with systemic biomarkers of pro- and anti-oxidant exposures. METHODS:
      Low, medium and high pro-oxidant exposures, and high, medium and low antioxidant
      exposures were assigned 0, 1 and 2 points, respectively and individual points for
      all exposures were then summed to calculate the overall score. Case and controls
      were compared using logistic regression analysis after adjusting for covariates.
      RESULTS: When OBS was treated as a continuous variable the adjusted odds ratios
      and 95% confidence intervals (CI) for each additional score point were the same:
      0.90 (95% CI: 0.83-0.97) for each study. When the OBS was divided into three
      approximately equal intervals, a comparison of the lowest to highest category
      showed similar adjusted ORs (95% CIs) of 0.34 (0.13-0.88) and 0.34 (0.14-0.86)
      for colorectal adenoma and prostate cancer, respectively. CONCLUSIONS: Our
      analyses provide support for the stated hypothesis that combined measures of pro-
      and anti-oxidant exposures may be associated with oxidative stress-related
      conditions.

PMID- 21074111
TI  - Geographic heterogeneity of prevalence of the human herpesvirus 8 in sub-Saharan
      Africa: clues about etiology.
AB  - PURPOSE: Human herpesvirus 8 (HHV-8, or Kaposi sarcoma [KS]-associated
      herpesvirus, KSHV) is a necessary but insufficient cause of KS, as KS develops in
      few HHV-8-infected persons. In sub-Saharan Africa, marked differences in the
      geographic distribution of HHV-8 and KS suggest that environmental cofactors
      influence HHV-8 transmission, control, and progression to KS. However, a direct
      comparison of HHV-8 prevalence estimates is complicated because studies used
      different serologic assays and analytic methods. We assessed HHV-8 seropositivity
      in several African countries with heterogeneous environments and varying KS
      incidence using a unified approach. METHODS: HHV-8 antibodies were measured among
      3196 adults (aged 20+ years) and 2404 children (aged <20 years) from five studies
      in four sub-Saharan countries in Africa. Serum samples were tested by the same
      laboratory using K8.1 and orf73 enzyme immunoassays. RESULTS: Children's HHV-8
      seropositivity ranged from 18.1% in Kampala, Uganda, to 33.8% in North Mara,
      Tanzania, increasing steeply with age in all populations. Among adults, HHV-8
      seropositivity ranged from 23.5% in Nigeria to 70.6% in rural West Nile, Uganda.
      It was higher in males and rural areas. CONCLUSIONS: Our data indicate that
      geographical exposures, gender, age, and factors correlated with rural residence
      impact HHV-8 seropositivity in sub-Saharan Africa.

PMID- 21074112
TI  - Cognitive demands of error processing associated with preparation and execution
      of a motor skill.
AB  - Maxwell et al. [Maxwell, J. P., Masters, R. S. W., Kerr, E., & Weedon, E. (2001).
      The implicit benefit of learning without errors. The Quarterly Journal of
      Experimental Psychology, 54A, 1049-1068. The implicit benefit of learning without
      errors. The Quarterly Journal of Experimental Psychology, 54A, 1049-1068]
      suggested that, following unsuccessful movements, the learner forms hypotheses
      about the probable causes of the error and the required movement adjustments
      necessary for its elimination. Hypothesis testing is an explicit process that
      places demands on cognitive resources. Demands on cognitive resources can be
      identified by measuring probe reaction times (PRT) and movement times. Lengthened
      PRT and movement times reflects increased cognitive demands. Thus, PRT and
      movement times should be longer following errors, relative to successful,
      movements. This hypothesis was tested using a motor skill (golf putting).
      Furthermore, the association between error processing and the preparation and
      execution phases of movement was examined. The data confirmed that cognitive
      demand is greater for trials following an error, relative to trials without an
      error. This effect was apparent throughout learning and in both the preparatory
      and execution phases of the movement. Cognitive effort also appeared to be higher
      during movement preparation, relative to movement execution.

PMID- 21074114
TI  - Setting stroke research priorities: The consumer perspective.
AB  - OBJECTIVES: To test a method of engaging consumers in research priority-setting
      using a quantitative approach and to determine consumer views on stroke research
      priorities for clinical practice recommendations with lower levels of evidence
      (Level III and Level IV) and expert consensus opinion as published in the
      Australian stroke clinical practice guidelines. DESIGN: Survey SETTING: Urban
      community SUBJECTS: Eighteen stroke survivors (n = 12) and carers (n = 6) who
      were members of the "Working Aged Group - Stroke" (WAGS) consumer support group.
      MAIN OUTCOME MEASURES: Phase I: Participants were asked whether recommendations
      were "worth" researching ("yes" or "no"); and, if researched, what potential
      impact they likely would have on patient outcomes. Phase II: Participants were
      asked to rank recommendations rated by more than 75% of participants in Phase I
      as "worth" researching and "highly likely" or "likely" to generate research with
      a significant effect on patient outcomes (n = 13) in order of priority for future
      stroke research. RESULTS: All recommendations were rated by at least half (n = 9,
      50%) of participants as "worth" researching. The majority (67% to 100%) rated all
      recommendations as "highly likely" or "likely" that research would have a
      significant effect on patient outcomes. Thirteen out of 20 recommendations were
      ranked for their research priorities. Recommendations under the topic heading
      Getting to hospital were ranked highest and Organization of care and Living with
      stroke were ranked as a lower priority for research. DISCUSSION/CONCLUSION: This
      study provided an example of how to involve consumers in research priority
      setting successfully using a quantitative approach. Stroke research priorities
      from the consumer perspective were different from those of health professionals,
      as published in the literature; thus, consumer opinion should be considered when
      setting research priorities.

PMID- 21074115
TI  - Creating an anticoagulant patient education class.
AB  - A patient education workgroup was developed on a progressive care
      medical/vascular surgical unit. The workgroup identified patient education needs
      regarding discharge education for postsurgical patients and those discharging
      with oral anticoagulants (OAC). Staff surveys aided the workgroup in identifying
      a need for additional discharge education for patients and families. After
      various methods of patient education were explored, it was determined the
      workgroup could best meet the needs of the patient population through a class
      format providing group discussion and interaction. Logistical details and class
      formatting were configured to meet both the needs of the patients and the nursing
      staff. Current institutional patient education pamphlets were used to develop the
      content for the class. Physician review and input were obtained during the
      development of the content. A patient education specialist was also consulted to
      ensure proper literacy levels were used. To meet the Joint Commission National
      Patient Safety Goal regarding anticoagulant safety, the content focused on home
      management, which included the following: knowledge of INR goal range, dietary
      factors, when to call the provider and safety precautions. Other topics to
      promote self-efficacy in anticoagulation therapy were also included in the
      content. Postclass evaluations completed by patients and families provided useful
      feedback for continuous improvement and patient satisfaction. Preliminary survey
      results indicate high patient satisfaction with the class. Plans include a
      quality improvement project to evaluate the effectiveness of the patient
      education class on OAC.

PMID- 21074116
TI  - Current modalities for abdominal aortic aneurysm repair: Implications for nurses.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) represent a significant health
      problem in the United States as more than 1 million people are afflicted and the
      prevalence is only expected to increase. Given that AAA rupture carries a high
      mortality rate, there is interest in repairing the aneurysm electively before
      aneurysm rupture. Two approaches to aneurysm repair are open repair and
      endovascular repair. However, limited data comparing the outcomes of these
      different methods exist. OBJECTIVE: A systematic review of recent clinical trials
      was conducted to identify and compare the short- and long-term clinical outcomes
      between open and endovascular repair. METHODS: Prospective, controlled trials
      published in the last 5 years were acquired using PubMed, Ovid, and Scopus
      databases. RESULTS: Four studies were identified during the search. Study trends
      suggest a perioperative advantage using endovascular repair. However, this
      advantage does not appear to be maintained in the long term. CONCLUSIONS: Each
      type of repair carries its own risk profile that is likely influenced by
      additional factors, such as the patient's age and comorbidities. It is critical
      that healthcare providers are aware of the risks associated with each approach in
      order to provide optimal patient care.

PMID- 21074117
TI  - Endovascular interventions for descending thoracic aortic aneurysms: The pivotal
      role of the clinical nurse in postoperative care.
AB  - Descending thoracic aortic aneurysms (dTAA) comprise 40% of all aneurysms arising
      from the thoracic aorta. Because rupture of thoracic aneurysms is associated with
      a 94% mortality rate, timely detection, surveillance and treatment is imperative.
      Endovascular stent-graft repair of thoracic aneurysms was first performed in 1992
      and has become an accepted treatment option for this condition in select
      candidates. There is an abundance of information for the care of patients after
      open surgical repair of dTAA. However, still relatively few written guidelines
      exist in the nursing literature for postoperative care and complications
      associated with endovascular stent-graft repair. The prevalence of aortic
      endografting, however, now makes it necessary for nurses to have a solid
      knowledge base in the operative procedure, complications and postoperative care
      for this patient population. Ideal candidates for aortic endografting undergo CTA
      or MRI preoperatively and fit a set of strict anatomic criteria to ensure proper
      delivery and fixation of the device. The early postoperative care focuses on
      minimizing pulmonary complications, paraplegia, renal failure and embolic
      complications such as stroke and limb ischemia through skilled nursing assessment
      and interventions. Late complications such as stent-graft migration, kinking,
      stent fracture and endoleak are often without symptoms, making it necessary for
      patients to be educated about these potential complications and to be encouraged
      to comply with lifelong follow up. This overview provides a sound cognitive
      framework for nurses practicing in a vascular surgery milieu.

PMID- 21074118
TI  - Review of an article: aspirin for primary prevention of cardiovascular events in
      people with diabetes. A position statement of the American Diabetes Association
      (ADA), a scientific statement of the American Heart Association(AHA), and an
      expert consensus document of the American College of Cardiology Foundation
      (ACCF). Diabetes Care, 33:6; June 2010; 1395-1402.

PMID- 21074119
TI  - Measuring the gap-it may well be worse than we thought.

PMID- 21074120
TI  - Dronedarone: from buzz to reality.

PMID- 21074121
TI  - Correlations between urinary excretion of catecholamines and electrocardiographic
      parameters of vagal hyperreactivity in infants with fainting spells. Implication
      of sympathetic hypotonia?
AB  - BACKGROUND: Vagal hyperreactivity (VHR) is a frequent etiology of infant fainting
      spells; but it is sometimes difficult to diagnose. A biochemical test would
      therefore be useful, especially as the oculocardiac reflex (OCR) test innocuity
      is not absolute. AIMS: To evaluate urinary excretions of norepinephrine,
      epinephrine and dopamine as markers for vagal hyperreactivity. METHODS: During
      check-up of 55 infants from 0.5 to 11 months of age, for discomfort episodes,
      including OCR and Holter recording, 24h urinary assays of total norepinephrine,
      epinephrine and dopamine were carried out to evaluate sympathetic activity.
      RESULTS: Epinephrine and norepinephrine urinary excretions were negatively
      correlated with VHR intensity, as measured by the OCR ECG parameters: RRmax, %
      cardiac deceleration and minimal frequency; dopamine excretion was not. When
      RRmax(OCR) was greater or equal to 800 ms, epinephrine urinary excretion tended
      to be less or equal to 9 nmol/mmol creatinine and norepinephrine excretion less
      or equal to 190 nmol/mmol creatinine. CONCLUSION: A delay in maturation of the
      sympathetic system and/or adrenomedullary glands with low secretion of
      norepinephrine and epinephrine inducing a desequilibrium of the
      sympathetic/parasympathetic balance may contribute to the fainting spells
      observed with VHR. Epinephrine and norepinephrine urinary excretions may provide
      informative complementary noninvasive markers for VHR.

PMID- 21074122
TI  - Observational study of adherence to European clinical practice guidelines for the
      management of acute coronary syndrome in revascularized versus non-revascularized
      patients - the CONNECT Study.
AB  - BACKGROUND: The CONNECT study compared clinician adherence to guideline
      recommended secondary prevention therapies prescribed at discharge for patients
      hospitalized for acute coronary syndrome (ACS) in those managed initially with
      percutaneous coronary intervention (PCI; revascularized) and those who did not
      undergo revascularization. METHODS: Patients aged greater than or equal to 18
      years, hospitalized for a documented ST-segment elevation or non-ST-segment
      elevation ACS, were enrolled consecutively over 1 month at 238 sites in France.
      RESULTS: Compared with revascularized patients (n=870), non-revascularized
      patients (n=706) were significantly older, and a greater proportion were women,
      had high-blood pressure, type-2 diabetes or a history of atherothrombotic or
      cardiac disease, but a smaller proportion had a history of coronary angioplasty.
      On discharge, non-revascularized patients were prescribed beta-blockers, aspirin,
      statins, angiotensin-converting enzyme inhibitors or adenosine diphosphate
      receptor antagonists less frequently than revascularized patients. An adherence
      score greater than or equal to 80% (at least four of the five recommended agents
      prescribed at discharge) was found in 96.7% of revascularized patients and 74.4%
      of non-revascularized patients (P<0.001). CONCLUSIONS: Despite a similar or even
      higher level of cardiovascular risk, non-revascularized ACS patients were
      prescribed guideline-recommended secondary prevention therapy less frequently
      than revascularized patients.

PMID- 21074123
TI  - Diagnostic value of contrast echocardiography in Tako-Tsubo cardiomyopathy.
AB  - BACKGROUND: Tako-Tsubo cardiomyopathy is a clinical entity mimicking acute
      coronary syndrome. Assessment of left ventricular function may be difficult using
      conventional echocardiography. AIMS: to characterize left ventricular systolic
      function using contrast echocardiography in Tako-Tsubo cardiomyopathy. METHODS:
      We prospectively studied 63 consecutive women admitted for suspected acute
      coronary syndrome who underwent coronary arteriography, biplane left ventricular
      angiography and conventional and contrast echocardiography; 25 women had Tako
      Tsubo cardiomyopathy (group 1), 25 women had proven coronary artery disease
      (group 2) and 13 women had no significant coronary lesion (group 3).
      Echocardiographic interpretation was performed by two observers: a physician
      trainee (observer 1) and an experienced investigator (observer 2). RESULTS: Left
      ventricular segments were assessed for wall motion abnormalities, which were
      present in 70 and 88% (observer 1) and in 91 and 99% (observer 2), using
      conventional and contrast echocardiography, respectively (P<0.0001). Accuracy for
      the diagnosis of Tako-Tsubo cardiomyopathy was improved significantly for both
      observers using contrast echocardiography: for observer 1, sensitivity was 56 and
      88%, respectively, using conventional and contrast echocardiography (P=0.01),
      whereas for observer 2, sensitivity was 72 and 96%, respectively (P=0.04).
      Interobserver agreement was excellent using contrast agent (kappa=0.85 vs 0.34
      using conventional echocardiography). The blinded review of left ventriculograms
      distinguished Tako-Tsubo cardiomyopathy from coronary artery disease correctly in
      96% of cases. CONCLUSIONS: Contrast echocardiography could be used in routine
      practice to replace left ventricular angiography in Tako-Tsubo cardiomyopathy.

PMID- 21074124
TI  - Telomere length and cardiovascular disease.
AB  - Telomeres are structures composed of deoxyribonucleic acid repeats that protect
      the end of chromosomes, but shorten with each cell division. They have been the
      subject of many studies, particularly in the field of oncology, and more recently
      their role in the onset, development and prognosis of cardiovascular disease has
      generated considerable interest. It has already been shown that these structures
      may deteriorate at the beginning of the atherosclerotic process, in the onset and
      development of arterial hypertension or during myocardial infarction, in which
      their length may be a predictor of outcome. As telomere length by its nature is a
      marker of cell senescence, it is of particular interest when studying the
      lifespan and fate of endothelial cells and cardiomyocytes, especially so because
      telomere length seems to be regulated by various factors notably certain
      cardiovascular risk factors, such as smoking, sex and obesity that are associated
      with high levels of oxidative stress. To gain insights into the links between
      telomere length and cardiovascular disease, and to assess the usefulness of
      telomere length as a new marker of cardiovascular risk, it seems essential to
      review the considerable amount of data published recently on the subject.

PMID- 21074125
TI  - Characteristics and management of acute ST-segment elevation myocardial
      infarctions occurring in ski resorts in the French Alps: Impact of an acute
      coronary care network.
AB  - BACKGROUND: Compliance with guidelines for the management of ST-segment elevation
      myocardial infarction (STEMI) may be difficult in hard-to-access areas. AIMS: to
      analyse the characteristics, management and outcome of STEMIs occurring at
      altitude in the French Alps and managed by mobile medical emergency units.
      METHODS: From January 2006 to December 2008, from the prospective RESURCOR
      registry, 114 patients with a STEMI of less than 12 hours' duration, occurring in
      a ski resort or at high altitude and managed by the RESURCOR care system, were
      identified. Baseline characteristics, treatments and in-hospital outcomes were
      analysed. RESULTS: Ninety-three per cent of patients were men; the mean age was
      57 years. STEMIs occurred during or less than 1 hour after physical activity in
      76.3% of cases (mainly during or after alpine/cross-country skiing). Killip class
      greater or equal to 2 and cardiac arrest were observed in 35% and 7.9% of cases,
      respectively. Fifty-two (45.6%) patients underwent thrombolysis and 62 (54.4%)
      had percutaneous coronary intervention (PCI). Median delays were: first call to
      treatment, 82 min (17-230 min); symptoms to treatment, 165 min (52-770 min). All
      delays were significantly longer for PCI than for thrombolysis. First call to
      treatment delay was less than 120 min in 98.1% of patients who underwent
      thrombolysis and in 51.6% who had PCI (P<0.0001). In-hospital survival was 96.5%.
      CONCLUSION: Altitude STEMIs happen mainly during sporting activities. Clinical
      presentation is often severe, but an emergency coronary care network allows rapid
      reperfusion. These findings emphasize the need for an efficient network for STEMI
      management in geographically difficult-to-access areas.

PMID- 21074128
TI  - Reversible cardiogenic shock in hypertrophic cardiomyopathy after alcohol septal
      ablation.

PMID- 21074126
TI  - Update on gene therapy for myocardial ischaemia and left ventricular systolic
      dysfunction or heart failure.
AB  - Despite considerable advances in pharmacological, surgical and technology-based
      cardiovascular therapy, left ventricular dysfunction and heart failure are
      increasingly prevalent health problems. Recent studies suggest that angiogenic
      gene therapy can restore perfusion in ischaemic myocardial tissue, and that the
      transfer of nonangiogenic genes may correct defects in calcium handling that
      contribute to abnormal contractile function in patients with heart failure;
      however, large clinical trials of gene therapy for treatment of left ventricular
      dysfunction and heart failure have yet to be completed, and only a small number
      of genes have been evaluated in patients. Researchers continue to investigate new
      genes, combinations of genes and approaches that combine gene and cell therapy,
      and to develop novel expression vectors and delivery systems; collectively, these
      refinements promise to improve both patient response and safety.

PMID- 21074127
TI  - Gene therapy for heart failure.
AB  - Despite the progress achieved in conventional treatment modalities, heart failure
      remains a major cause of mortality and morbidity. The identification of novel
      signaling pathways has provided a solid scientific rationale which has stimulated
      preclinical development of gene-based therapies for heart failure. Advances in
      somatic gene transfer technologies have been crucial to the advent of the first
      human clinical trials which are currently in progress. As these and other trials
      of gene transfer-based therapies are initiated, these approaches have generated
      excitement and hope for novel treatments for cardiovascular disease. In this
      review, we present a summary of advancements in construction of different vectors
      and methods of delivery that have been used for specific myocardial gene
      delivery. In addition, we will show results from studies focusing on the use of
      gene therapy to target heart failure mechanisms in animal models of cardiac
      dysfunction. Finally, we discuss the limited but highly promising results from
      clinical studies that have served as catalysts to translate preclinical
      achievements towards new treatment modalities for heart failure.

PMID- 21074129
TI  - A case of curable pulmonary hypertension.

PMID- 21074130
TI  - Metastatic carcinoid tumour of the heart.

PMID- 21074131
TI  - Anomalous origin of the pulmonary artery from the ascending aorta in a neonate,
      assessed by two-dimensional echocardiography.

PMID- 21074132
TI  - 2009 pandemic influenza A (H1N1) virus infection in postpartum women in
      California.
AB  - OBJECTIVE: The objective of the study was to characterize severe illness because
      of the 2009 pandemic influenza A (H1N1) infection in postpartum women. STUDY
      DESIGN: We reviewed case reports of infected hospitalized postpartum (<= 6 months
      from delivery) women identified through statewide surveillance in California.
      From April 23 through August 11, 2009, all hospitalizations and/or deaths were
      reported. After August 11, reporting was limited to cases requiring intensive
      care or deaths. RESULTS: From April 23 to December 31, 2009, 15 cases were
      reported; 11 (73%) had symptom onset within 7 days postpartum. Of 10 hospitalized
      cases reported through August 11, 4 required intensive care, 3 required
      mechanical ventilation, and 2 died. Of 5 cases requiring intensive care reported
      after August 11, all required mechanical ventilation and 1 died. Overall, 6 (43%)
      received antivirals within 48 hours of symptom onset. CONCLUSION: The 2009 H1N1
      can cause severe illness in postpartum women, especially in the first week
      following delivery.

PMID- 21074133
TI  - Proteomic identification of serum peptides predicting subsequent spontaneous
      preterm birth.
AB  - OBJECTIVE: We sought to identify serum markers of subsequent spontaneous preterm
      birth (SPTB) in asymptomatic women prior to labor. STUDY DESIGN: Serum proteomics
      was applied to sera from 80 pregnant women sampled at 24 weeks and an additional
      80 pregnant women sampled at 28 weeks. Half had uncomplicated pregnancies and
      half had SPTB. RESULTS: Three specific peptides arising from inter-alpha-trypsin
      inhibitor heavy chain 4 protein were significantly reduced in women at 24 and 28
      weeks having subsequent SPTB. The most discriminating peptide had a sensitivity
      of 65.0% and specificity of 82.5%; odds ratio, 8.8; and 95% confidence interval,
      3.1-24.8. A combination of the 3 new biomarkers and 6 previously studied
      biomarkers increased sensitivity to 86.5%, with a specificity of 80.6% at 28
      weeks. CONCLUSION: Three novel serum markers of SPTB have been identified using
      serum proteomics. Using a combination of these new markers with additional
      markers, women at risk of SPTB can be identified weeks prior to SPTB.

PMID- 21074134
TI  - Obstetrician-gynecologists' views on contraception and natural family planning: a
      national survey.
AB  - OBJECTIVE: The objective of the study was to characterize beliefs about
      contraception among obstetrician-gynecologists. STUDY DESIGN: National mailed
      survey of 1800 US obstetrician-gynecologists. Criterion variables were whether
      physicians have a moral or ethical objection to, and whether they would offer, 6
      common contraceptive methods. Covariates included physician demographic and
      religious characteristics. RESULTS: One thousand one hundred fifty-four of 1760
      eligible obstetrician-gynecologists responded (66%). Some obstetrician
      gynecologists object to intrauterine devices (4.4% object, 3.6% would not offer),
      progesterone implants and/or injections (1.7% object, 2.1% would not offer),
      tubal ligations (1.5% object, 1.5% would not offer), oral contraceptive pills
      (1.3% object, 1.1% would not offer), condoms (1.3% object, 1.8% would not offer),
      and the diaphragm or cervical cap with spermicide (1.3% object, 3.3% would not
      offer). Religious physicians were more likely to object (odds ratio, 7.4) and to
      refuse to provide a contraceptive (odds ratio, 1.9). CONCLUSION: Controversies
      about contraception are ongoing but among obstetrician-gynecologists, objections
      and refusals to provide contraceptives are infrequent.

PMID- 21074135
TI  - Expectant management of preterm premature rupture of membranes: is it all about
      gestational age?
AB  - OBJECTIVE: We sought to compare neonatal outcome in cases of uncomplicated
      preterm premature rupture of membranes (PPROM) (ie, no evidence of clinical
      chorioamnionitis, placental abruption, or fetal distress) with that of
      spontaneous preterm deliveries (PTDs) and to determine the effect of the latency
      period. STUDY DESIGN: The study group included women with PPROM at gestational
      age 280(/)7-336(/)7 weeks (n = 488). Neonatal outcome was compared with a matched
      control group of women with spontaneous PTD (n = 1464). RESULTS: Neonates in the
      uncomplicated PPROM group were at increased risk for composite adverse outcome
      (53.7% vs 42.0%; P < .001), mortality (1.6% vs 0.0%; P < .001), respiratory
      morbidity (32.8% vs 26.4%; P = .006), necrotizing enterocolitis, jaundice,
      hypoglycemia, hypothermia, and polycythemia. Neonatal adverse outcome was more
      likely in cases of latency period >7 days, oligohydramnios, male fetus, and
      nulliparity. CONCLUSION: Consultation regarding prematurity-related morbidity in
      infants exposed to uncomplicated PPROM cannot be extrapolated from PTDs and
      should be stratified by the duration of the latency period and the other risk
      factors identified in the current study.

PMID- 21074136
TI  - Prognostic analysis of ovarian cancer associated with endometriosis.
AB  - OBJECTIVE: The objective of the study was to evaluate the prognosis of ovarian
      cancer arising in endometriosis. STUDY DESIGN: We retrospectively compared 42
      cases of endometriosis-associated ovarian cancer (EAOC) with 184 cases of ovarian
      carcinoma without endometriosis (OC). RESULTS: The median age in the EAOC group
      was 52 vs 59 years in OC (P < .05). In comparison with OC, the EAOC patients were
      more likely to have low-grade (21% vs 8%; P = .04) and early-stage tumors
      (International Federation of Gynecology and Obstetrics I and II combined) (49% vs
      24%; P = .002). Clear cell (21% vs 2%) and endometrioid (14% vs 3%) tumors were
      more frequent in EAOC, whereas mucinous tumors were more prevalent in OC (P =
      .001). The median survival (199 vs 62 months) and the 5 year survival (62% vs
      51%) were better for EAOC when compared with OC (P = .038). After controlling for
      age, stage, grade, and treatment, association with endometriosis was not an
      independent predictor of better survival in ovarian cancer. CONCLUSION: As such,
      EAOC has a much better survival rate than OC. This could be explained by the
      higher prevalence of early-stage and low-grade tumors in EAOC when compared with
      OC.

PMID- 21074137
TI  - Adverse childhood experiences and repeat induced abortion.
AB  - OBJECTIVE: The objective of the study was to characterize the backgrounds of
      women who have repeat abortions. STUDY DESIGN: In a cross-sectional study of 259
      women (mean age, 35.2 +/- 5.6 years), the relation between adverse experiences in
      childhood and risk of having 2 or more abortions vs 0 or 1 abortion was examined.
      Self-reported adverse events occurring between the ages of 0 and 12 years were
      summed. RESULTS: Independent of confounding factors, women who experienced more
      abuse, personal safety, and total adverse events in childhood were more likely to
      have 2 or more abortions vs 0 abortions (odds ratio [OR], 2.56; 95% confidence
      interval [CI], 1.15-5.71; OR, 2.74; 95% CI, 1.29-5.82; and OR, 1.59; 95% CI, 1.21
      2.09, respectively) and vs 1 abortion (OR, 5.83; 95% CI, 1.71-19.89; OR, 2.23;
      95% CI, 1.03-4.81; and OR, 1.37; 95% CI, 1.04-1.81, respectively). Women who
      experienced more family disruption events in childhood were more likely to have 2
      or more abortions vs 0 abortions (OR, 1.75; 95% CI, 1.14-2.69) but not vs 1
      abortion (OR, 1.16; 95% CI, 0.79-1.70). CONCLUSION: Women who have repeat
      abortions are more likely to have experienced childhood adversity than those
      having 0 or 1 abortion.

PMID- 21074138
TI  - Cost-effectiveness and accuracy of prenatal Down syndrome screening strategies:
      should the combined test continue to be widely used?
AB  - OBJECTIVE: We analyzed the cost-effectiveness (CE) and performances of commonly
      used prenatal Down syndrome (DS) screening strategies. STUDY DESIGN: We performed
      computer simulations to compare 8 screening options by applying empirical data
      from Serum, Urine, and Ultrasound Screening Study trials on the population of
      110,948 pregnancies. Screening strategies outcomes, CE ratios, and incremental CE
      ratios were measured. RESULTS: The most CE DS screening strategy was the
      contingent screening method (CE ratio of Can$26,833 per DS case). Its incremental
      CE ratio compared to the second-most CE strategy (serum integrated screening) was
      Can$3815 per DS birth detected. Among the procedures respecting guidelines, our
      results identified the combined test as the screening strategy with the highest
      CE ratio (Can$47,358) and the highest number of procedure-related euploid
      miscarriages (n = 71). CONCLUSION: In regard to CE, contingent screening is the
      best choice. The combined test, which is the most popular screening strategy,
      shows many limitations.

PMID- 21074139
TI  - The effects of postnatal estrogen therapy on brain development in preterm
      baboons.
AB  - OBJECTIVE: Estrogen receptors are present within the fetal brain, suggesting that
      estrogens may exert an influence on cerebral development. Loss of placentally
      derived estrogen in preterm birth may impair development. STUDY DESIGN: Baboons
      were delivered at 125 days of gestation (term approximately 185 days), randomly
      allocated to receive estradiol (n = 10) or placebo (n = 8), and ventilated for 14
      days. Brains were assessed for developmental and neuropathological parameters.
      RESULTS: Body and brain weights were not different between groups, but the
      brain/body weight ratio was increased (P < .05) in estradiol-treated animals.
      There were no differences (P > .05) between groups in any neuropathological
      measure in either the forebrain or cerebellum. There were no intraventricular
      hemorrhages; 1 estradiol animal displayed ectactic vessels in the subarachnoid
      space. CONCLUSION: Brief postnatal estradiol administration to primates does not
      pose an increased risk of injury or impaired brain development.

PMID- 21074140
TI  - Nighttime delivery and risk of neonatal encephalopathy.
AB  - OBJECTIVE: The objective of the study was to determine the relationship between
      nighttime delivery and neonatal encephalopathy (NE). STUDY DESIGN: The design of
      the study was a retrospective population-based cohort of 1,864,766 newborns at a
      gestation of 36 weeks or longer in California, 1999-2002. We determined the risk
      of NE associated with nighttime delivery (7:00 (PM) to 6:59 (AM)). RESULTS: Two
      thousand one hundred thirty-one patients had NE (incidence 1.1 per 1000 births).
      Nighttime delivery was associated with increased NE (odds ratio [OR], 1.13; 95%
      confidence interval [CI], 1.03-1.20), birth asphyxia (OR, 1.18; 95% CI, 1.08
      1.29), and neonatal seizures (OR, 1.17; 95% CI, 1.07-1.28). In adjusted analyses,
      nighttime delivery was an independent risk factor for NE (OR, 1.10; 95% CI, 1.01
      1.21), as were severe intrauterine growth retardation (OR, 3.8; 95% CI, 3.1-4.8);
      no prenatal care (OR, 2.0; 95% CI, 1.4-2.9); primiparity (OR, 1.5; 95% CI, 1.4
      1.7); advanced maternal age (OR, 1.3; 95% CI, 1.16-1.45); and infant male sex
      (OR, 1.3; 95% CI, 1.2-1.4). CONCLUSION: Future studies of time of delivery may
      generate new strategies to reduce the burden of NE.

PMID- 21074141
TI  - Correlation between safety assessments in the driver-car interaction design
      process.
AB  - With the functional revolution in modern cars, evaluation methods to be used in
      all phases of driver-car interaction design have gained importance. It is crucial
      for car manufacturers to discover and solve safety issues early in the
      interaction design process. A current problem is thus to find a correlation
      between the formative methods that are used during development and the summative
      methods that are used when the product has reached the customer. This paper
      investigates the correlation between efficiency metrics from summative and
      formative evaluations, where the results of two studies on sound and navigation
      system tasks are compared. The first, an analysis of the J.D. Power and
      Associates APEAL survey, consists of answers given by about two thousand
      customers. The second, an expert evaluation study, was done by six evaluators who
      assessed the layouts by task completion time, TLX and Nielsen heuristics. The
      results show a high degree of correlation between the studies in terms of task
      efficiency, i.e. between customer ratings and task completion time, and customer
      ratings and TLX. However, no correlation was observed between Nielsen heuristics
      and customer ratings, task completion time or TLX. The results of the studies
      introduce a possibility to develop a usability evaluation framework that includes
      both formative and summative approaches, as the results show a high degree of
      consistency between the different methodologies. Hence, combining a quantitative
      approach with the expert evaluation method, such as task completion time, should
      be more useful for driver-car interaction design.

PMID- 21074142
TI  - Synthetic ameloblastin peptide stimulates differentiation of human periodontal
      ligament cells.
AB  - OBJECTIVE: This study investigates the effect of the N-terminal region of a
      synthetic porcine ameloblastin peptide on the proliferation and differentiation
      of human periodontal ligament cells (PDLC). DESIGN: We used a cell counter to
      assess the effect of ameloblastin peptides on the proliferation of PDLC. To
      investigate the effect of ameloblastin peptides on the differentiation of PDLC,
      we examined quantitative analysis of alkaline phosphatase (ALP) activity by the
      Bessey-Lowry enzymological method, mineral nodule formation by Dahl's method, and
      expression of mineralization-related genes by RT-PCR. We used an anti
      ameloblastin antibody to determine whether stimulation of ALP activity was caused
      by the peptide. RESULTS: At all concentrations examined, the effect of the
      ameloblastin peptide on cell proliferation was not significantly different
      compared with the control. However, the peptide significantly stimulated ALP
      activity in a dose-dependent manner. ALP activity was significantly inhibited by
      an anti-ameloblastin antibody, which caused ALP levels to revert to their
      approximate levels in the untreated condition. At concentrations greater than
      1ng/ml, the peptide promoted mineralized nodule formation of PDLC. And the
      peptide induced higher expressions of ALP and bone sialoprotein (BSP) than the
      control. CONCLUSION: Our results show that the ameloblastin peptide upregulate
      ALP and BSP levels and can enhance calcification of PDLC. Thus, we suggest that
      the N-terminal synthetic ameloblastin peptide promotes the differentiation
      activity of PDLC.

PMID- 21074143
TI  - Antibacterial activity and cytotoxicity of two novel cross-linking antibacterial
      monomers on oral pathogens.
AB  - OBJECTIVES: The antibacterial activity and cytotoxicity of two novel cross
      linking antibacterial monomers, 2-methacryloxylethyl dodecyl methyl ammonium
      bromide (MAE-DB) and 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE
      HB) were tested in this study. DESIGN: The minimum inhibitory concentration (MIC)
      and the minimum bactericidal concentration (MBC) of unpolymerized MAE-DB and MAE
      HB against eight strains of oral bacteria were tested using a broth dilution
      test. Time-kill determinations were performed to examine the kinetics of
      unpolymerized MAE-DB and MAE-HB against Streptococcus mutans UA159 and
      Streptococcus sanguinis ATCC6715. Bacterial morphology was observed using a field
      emission scanning electron microscope (Fe-SEM). The cytotoxicity of unpolymerized
      two new monomers and Bis-GMA on the human gingival fibroblast cell line H2620 was
      assessed using a methyl thiazolyl tetrazolium assay. RESULTS: Unpolymerized MAE
      DB and MAE-HB showed strong bactericidal activity against oral bacteria. The MBC
      value of MAE-DB ranged from 12.2 to 24.4MUg/ml and the MBC value of MAE-HB ranged
      from 6.2 to 48.8MUg/ml. Time-kill determinations indicated that unpolymerized MAE
      DB and MAE-HB had rapid killing effects against S. mutans UA159 and S. sanguinis
      ATCC6715 at the concentration of 4* MBC. The Fe-SEM observation showed that MAE
      DB and MAE-HB could disturb the integrity of bacteria and cause lysis of
      bacterial cells. The median lethal concentration values on human gingival
      fibroblast for both monomers were between 10 and 20MUg/ml, and greater than that
      of Bis-GMA. CONCLUSIONS: Unpolymerized MAE-DB and MAE-HB monomers had strong
      bactericidal activity against eight strains of oral bacteria. Their
      cytotoxicities were less than that of Bis-GMA.

PMID- 21074144
TI  - Contributions of striatal dopamine signaling to the modulation of cognitive
      flexibility.
AB  - BACKGROUND: Although cognitive flexibility is mediated by different areas of the
      prefrontal cortex, evidence from patients with Parkinson's disease suggests an
      additional involvement of striatal dopamine (DA) signaling. Because both dorsal
      and ventral striatum receive prefrontal cortex projections, it is unclear whether
      DA signaling to either one or both of these regions is required for cognitive
      flexibility. METHODS: Cognitive flexibility was examined with a water U-maze
      paradigm in which mice had to shift from an initially acquired escape strategy to
      a new strategy or to reverse the initially learned strategy. We tested mice with
      conditionally inactive tyrosine hydroxylase genes that can be activated by Cre
      recombinase. With region-specific viral gene therapy we selectively restricted DA
      signaling to either dorsal or ventral striatum. RESULTS: Restricting DA signaling
      to the ventral striatum did not impair learning of the initial strategy or
      reversal-learning but strongly disrupted strategy-shifting. In contrast, mice
      with DA signaling restricted to the dorsal striatum had intact learning of the
      initial strategy, reversal-learning, and strategy-shifting. CONCLUSIONS: Dopamine
      signaling in both dorsal and ventral striatum is sufficient for reversal
      learning, whereas only DA signaling in the dorsal striatum is sufficient for the
      more demanding strategy-shifting task.

PMID- 21074145
TI  - Word learning does not end at fast-mapping: evolution of verb meanings through
      reorganization of an entire semantic domain.
AB  - This paper explores the process through which children sort out the relations
      among verbs belonging to the same semantic domain. Using a set of Chinese verbs
      denoting a range of action events that are labeled by carrying or holding in
      English as a test case, we looked at how Chinese-speaking 3-, 5-, and 7-year-olds
      and adults apply 13 different verbs to a range of carrying/holding events. We
      asked how children learning Chinese originally divide and label the semantic
      space in this domain, how they discover the boundaries between different words,
      and how the meanings of verbs in the domain as a whole evolve toward the
      representations of adults. We also addressed the question of what factors make
      verb meaning acquisition easy or hard. Results showed that the pattern of
      children's verb use is largely different from that of adults and that it takes a
      long time for children to be able to use all verbs in this domain in the way
      adults do. We also found that children start to use broad-covering and frequent
      verbs the earliest, but use of these verbs tends to converge on adult use more
      slowly because children could not use these verbs as adults did until they had
      identified boundaries between these verbs and other near-synonyms with more
      specific meanings. This research highlights the importance of systematic
      investigation of words that belong to the same domain as a whole, examining how
      word meanings in a domain develop as parts of a connected system, instead of
      examining each word on its own: learning the meaning of a verb invites
      restructuring of the meanings of related, neighboring verbs.

PMID- 21074146
TI  - The size congruity effect: is bigger always more?
AB  - When comparing digits of different physical sizes, numerical and physical size
      interact. For example, in a numerical comparison task, people are faster to
      compare two digits when their numerical size (the relevant dimension) and
      physical size (the irrelevant dimension) are congruent than when they are
      incongruent. Two main accounts have been put forward to explain this size
      congruity effect. According to the shared representation account, both numerical
      and physical size are mapped onto a shared analog magnitude representation. In
      contrast, the shared decisions account assumes that numerical size and physical
      size are initially processed separately, but interact at the decision level. We
      implement the shared decisions account in a computational model with a dual route
      framework and show that this model can simulate the modulation of the size
      congruity effect by numerical and physical distance. Using other tasks than
      comparison, we show that the model can simulate novel findings that cannot be
      explained by the shared representation account.

PMID- 21074147
TI  - Accessing the unsaid: the role of scalar alternatives in children's pragmatic
      inference.
AB  - When faced with a sentence like, "Some of the toys are on the table", adults, but
      not preschoolers, compute a scalar implicature, taking the sentence to imply that
      not all the toys are on the table. This paper explores the hypothesis that
      children fail to compute scalar implicatures because they lack knowledge of
      relevant scalar alternatives to words like "some". Four-year-olds were shown
      pictures in which three out of three objects fit a description (e.g., three
      animals reading), and were asked to evaluate statements that relied on context
      independent alternatives (e.g., knowing that all is an alternative to some for
      the utterance "Some of the animals are reading") or contextual alternatives
      (e.g., knowing that the set of all three visible animals is an alternative to a
      set of two for the utterance "Only the cat and the dog are reading"). Children
      failed to reject the false statements containing context-independent scales even
      when the word only was used (e.g., only some), but correctly rejected equivalent
      statements containing contextual alternatives (e.g., only the cat and dog). These
      results support the hypothesis that children's difficulties with scalar
      implicature are due to a failure to generate relevant alternatives for specific
      scales. Consequences for number word learning are also discussed.

PMID- 21074148
TI  - The GROOP effect: groups mimic group actions.
AB  - Research on perception-action links has focused on an interpersonal level,
      demonstrating effects of observing individual actions on performance. The present
      study investigated perception-action matching at an inter-group level. Pairs of
      participants responded to hand movements that were performed by two individuals
      who used one hand each or they responded to hand movements performed by an
      individual who used both hands. Apart from the difference in the number of
      observed agents, the observed hand movements were identical. If co-actors form
      action plans that specify the actions to be performed jointly, then participants
      should have a stronger tendency to mimic group actions than individual actions.
      Confirming this prediction, the results showed larger mimicry effects when groups
      responded to group actions than when groups responded to otherwise identical
      individual actions. This suggests that representations of joint tasks modulate
      automatic perception-action links and facilitate mimicry at an inter-group level.

PMID- 21074149
TI  - Pseudohypacusis in childhood and adolescence is associated with increased gray
      matter volume in the medial frontal gyrus and superior temporal gyrus.
AB  - Pseudohypacusis is a somatoform disorder characterized by hearing loss with
      discrepancies between pure-tone audiometry and auditory brainstem response (ABR),
      but the underlying neuronal mechanisms remain unclear. Using voxel-based
      morphometry (VBM) with magnetic resonance (MR) imaging for 14 unmedicated, right
      handed patients and 35 healthy control subjects, we investigated whether
      functional hearing loss was associated with discernible changes of brain
      morphology. Group differences in gray matter volume (GMV) were assessed using
      high-resolution, T1-weighted, volumetric MR imaging datasets (3T Trio scanner;
      Siemens AG) and analyzed with covariant factors of age, sex, socioeconomic status
      (SES), and total GMV, which was increased by 27.9% in the left medial frontal
      gyrus (MFG) (Brodmann area 10) (p=.001, corrected cluster level) and by 14.4% in
      the right superior temporal gyrus (STG) and the adjacent middle temporal gyrus
      (MTG) (BA42 to 21) (p=.009, corrected cluster level) in patients with
      pseudohypacusis. The GMV in the right STG (BA42) and verbal intelligence quotient
      (IQ) were correlated significantly with the Wechsler Intelligence Scale for
      Children - Third Edition (WISC-III) (beta=-.57, p<.0001) and level of SES (beta=
      .55, p<.0001). The present findings suggest that the development of the auditory
      association cortex involved in language processing is affected, causing
      insufficient pruning during brain development. We therefore assert that
      differences in the neuroanatomical substrate of pseudohypacusis subjects result
      from a developmental disorder in auditory processing.

PMID- 21074150
TI  - Comparison of levonorgestrel intrauterine system versus hysterectomy on efficacy
      and quality of life in patients with adenomyosis.
AB  - OBJECTIVE: To compare the levonorgestrel intrauterine system (LNG-IUS) with
      hysterectomy in patients with adenomyosis and to study the effects of both
      treatments on quality of life (QOL). DESIGN: Prospective randomized clinical
      trial. SETTING: Women's health teaching and research hospital. PATIENT(S): Eighty
      six patients (43 patients for each group) were enrolled, but only 75 women
      continued the study. INTERVENTION(S): Women interpreted as having adenomyosis on
      transvaginal ultrasound and magnetic resonance imaging were assigned to receive
      either LNG-IUS or hysterectomy. MAIN OUTCOME MEASURE(S): Clinical measures of
      menstrual bleeding as number of used pads/day during menstruation, hemoglobin
      levels, and health-related QOL variables were assessed. Each woman was followed
      up for 1 year after treatment. RESULT(S): LNG-IUS increased the hemoglobin levels
      at the sixth month and first year of the treatment to the comparable levels with
      hysterectomy. When pretreatment and post-treatment QOL scores of groups were
      compared, three of the five mean domain scores (physical, environmental,
      environmental-TR) were increased in patients treated with hysterectomy, while in
      patients managed with LNG-IUS, all five mean domain scores were increased.
      CONCLUSION(S): It seems that LNG-IUS demonstrates significant and comparable
      improvements in hemoglobin levels to hysterectomy in treating adenomyosis
      associated menorrhagia during the first year. Although both treatments lead to
      improvements in health-related QOL, LNG-IUS seems to have superior effects on
      psychological and social life. It may be a promising alternative therapy to
      hysterectomy.

PMID- 21074151
TI  - Anti-mullerian hormone (AMH) and repetitive oocyte donation.

PMID- 21074153
TI  - Adolescent varicocele: improved sperm function after varicocelectomy.
AB  - OBJECTIVE: To assess the effect of varicocelectomy on sperm function (DNA
      integrity and mitochondrial activity) and levels of lipid peroxidation in seminal
      plasma of adolescents. DESIGN: Prospective study. SETTING: Patients recruited
      from a local public school. PATIENT(S): Adolescents (14-19 years old), Tanner
      stages IV or V with varicocele grades II or III, attending a local public school.
      INTERVENTION(S): Two semen collections with a one week interval between
      collections before bilateral varicocele repair using subinguinal microsurgical
      varicocelectomy, and two semen collections with a one week interval between
      collections three months after the surgery. MAIN OUTCOME MEASURE(S): Rate of
      sperm DNA fragmentation as assessed by the Comet assay and categorized as classes
      I (no DNA fragmentation) to IV (high DNA fragmentation). Rate of mitochondrial
      activity as assessed by the diaminobenzidine assay and categorized as grades I
      (all mitochondria active) to IV (all mitochondria inactive). Levels of lipid
      peroxidation in seminal plasma by a colorimetric method that quantifies a lipid
      peroxidation subproduct (malondialdehyde). RESULT(S): Concerning DNA integrity,
      the samples after varicocelectomy showed more spermatozoa with intact nuclear DNA
      (grade I) and less spermatozoa with Comet grades II, III, and IV. Regarding
      mitochondrial activity, the samples after varicocelectomy showed less cells with
      inactive mitochondria (class III). No differences were observed in classes I, II,
      and IV. Concerning lipid peroxidation, no significant differences were observed.
      CONCLUSION(S): This study was able to demonstrate that varicocelectomy in
      adolescents is associated with increased sperm DNA integrity and mitochondrial
      activity. However, levels of seminal products of lipid degradation
      (malondialdehyde) are not different.

PMID- 21074154
TI  - Stimulation of the young poor responder: comparison of the luteal
      estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral
      contraceptive microdose leuprolide.
AB  - OBJECTIVE: To evaluate in vitro fertilization (IVF) cycle outcomes in young poor
      responders treated with a luteal estradiol/gonadotropin-releasing hormone
      antagonist (E(2)/ANT) protocol versus an oral contraceptive pill microdose
      leuprolide protocol (OCP-MDL). DESIGN: Retrospective cohort. SETTING: Academic
      practice. PATIENT(S): Poor responders: 186 women, aged <35 years undergoing IVF
      with either E(2)/ANT or OCP-MDL protocols. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Clinical pregnancies, oocytes retrieved, cancellation rate.
      RESULT(S): Patients in the E(2)/ANT group had a greater gonadotropin requirement
      (71.9 +/- 22.2 vs. 57.6 +/- 25.7) and lower E(2) level (1,178.6 +/- 668 vs. 1,627
      +/- 889), yet achieved similar numbers of oocytes retrieved and fertilized, and a
      greater number of embryos transferred (2.3 +/- 0.9 vs. 2.0 +/- 1.1) with a better
      mean grade (2.14 +/- .06 vs. 2.7 +/- 1.8) compared with the OCP/MDL group. The
      E2/ANT group exhibited a trend toward improved implantation rates (30.5% vs.
      21.1%) and ongoing pregnancy rates per started cycle: 44 out of 117 (37%) versus
      17 out of 69 (25%). CONCLUSION(S): Poor responders aged <35 years may be treated
      with the aggressive E(2)/ANT protocol to improve cycle outcomes. Both protocols
      remain viable options for this group. Adequately powered, randomized clinical
      comparison appears justified.

PMID- 21074155
TI  - Selection of viable spermatozoa from testicular biopsies: a comparative study
      between pentoxifylline and hypoosmotic swelling test.
AB  - OBJECTIVE: To compare fertilization, cleavage, and pregnancy outcome using
      pentoxifylline and a hypoosmotic swelling (HOS) test to select viable spermatozoa
      from testicular biopsy specimens. DESIGN: Open, comparative, prospective study.
      SETTING: G.S. Medical College and Fertility clinic, Mumbai, India. PATIENT(S): A
      total of 50 couples enrolled for infertility treatment having a male factor
      indication of nonobstructive azoospermia. INTERVENTION(S): Assessment of viable
      spermatozoa using pentoxifylline and using an HOS test from a population of
      nonmotile spermatozoa obtained from testicular biopsies. MAIN OUTCOME MEASURE(S):
      Comparison of fertilization, cleavage, and clinical pregnancy rates using viable
      sperms recovered using pentoxifylline and an HOS test. RESULT(S): Viable
      spermatozoa were obtained in both the study groups. Significantly higher
      fertilization rates (pentoxifylline 62.05% vs. HOS 41.07%) and clinical pregnancy
      rates (pentoxifylline 32% vs. HOS 16%) were observed. There was no significant
      difference in cleavage rates among both groups. CONCLUSION(S): We found that
      obtaining viable spermatozoa using pentoxifylline was more effective in terms of
      fertilization and pregnancies than obtaining it through an HOS test.

PMID- 21074156
TI  - Tuning of an optimal fuzzy PID controller with stochastic algorithms for
      networked control systems with random time delay.
AB  - An optimal PID and an optimal fuzzy PID have been tuned by minimizing the
      Integral of Time multiplied Absolute Error (ITAE) and squared controller output
      for a networked control system (NCS). The tuning is attempted for a higher order
      and a time delay system using two stochastic algorithms viz. the Genetic
      Algorithm (GA) and two variants of Particle Swarm Optimization (PSO) and the
      closed loop performances are compared. The paper shows that random variation in
      network delay can be handled efficiently with fuzzy logic based PID controllers
      over conventional PID controllers.

PMID- 21074157
TI  - Evaluation of the Victorian state adult pre-hospital trauma triage criteria.
AB  - BACKGROUND: Pre-hospital trauma triage criteria are used to expedite the
      transport of severely injured patients to major trauma services. The current
      Victorian adult pre-hospital trauma triage criteria consist of physiological,
      anatomical and mechanistic elements. The purpose of this study was to evaluate
      the performance of the current triage criteria and, if necessary propose refined
      criteria to improve the under and over-triage rates. METHODS: The study was
      conducted in Melbourne, Victoria, which has a fully integrated State Trauma
      System. Trauma data was sourced from the pre-hospital Victorian Ambulance
      Clinical Information System and the Victorian State Trauma Registry. Confirmed
      major trauma was defined at hospital discharge as one or more of death, ISS>15,
      ICU ventilation or urgent surgery. Data was matched through probabilistic
      linkage. The triage criteria were evaluated using multivariate logistic
      regression and classification tree modelling. Diagnostic statistics, including
      sensitivity and specificity were calculated to assess triage performance.
      RESULTS: Over 12-months there were 1166 'confirmed major trauma' patients and
      44,166 'non-major trauma' patients. Evaluation showed the current triage criteria
      needed refinement, and multiple revised pre-hospital trauma triage models were
      constructed. Based on the best overall combination of diagnostic statistics, a
      revised model was chosen with a sensitivity of 97.8% (vs. 95.3% in the current
      model), a specificity of 82.7% (vs. 62.7%) and an accuracy of 83.0% (vs. 63.4%).
      The over-triage rate was 17.3% (vs. 37.3%) and the under-triage rate was 2.2%
      (vs. 4.7%). CONCLUSIONS: Evaluation showed that the specificity and sensitivity
      of the current trauma triage criteria could be improved. The implementation of a
      revised triage model should identify more confirmed major trauma patients.
      Likewise, over-triage of non-major trauma patients to major trauma services would
      be significantly reduced. The refined criteria should also decrease discretionary
      decision-making by paramedics in the field.

PMID- 21074158
TI  - Mitochondrial uncoupling protein gene cluster variation (UCP2-UCP3) and the risk
      of incident type 2 diabetes mellitus: the Women's Genome Health Study.
AB  - OBJECTIVE: Uncoupling protein 2, mitochondrial, (UCP2) gene variation has
      recently been implicated in type 2 diabetes mellitus (T2DM). To date, no
      prospective epidemiological data are available. METHODS: The association between
      14 UCP (UCP2-UCP3) gene cluster tagging-SNPs and incident T2DM was investigated
      in 22,715 Caucasian participants of the prospective Women's Genome Health Study.
      All were free of known cardiovascular disease and diabetes at baseline. During a
      13-year follow-up period, 1445 participants developed an incident T2DM.
      Multivariable Cox regression analysis was performed to investigate the
      relationship between genotypes and T2DM risk assuming an additive model.
      Stratified analysis by smoking status, and haplotype analysis were also
      performed. RESULTS: No evidence for an association of any of the tagging-SNPs
      tested with T2DM risk. Further investigation using stratified analysis, and
      haplotype-based approach showed similar null findings. CONCLUSION: The present
      investigation suggests that the UCP gene cluster variation may not be useful
      predictor for T2DM risk assessment.

PMID- 21074159
TI  - Moment arms of the human neck muscles in flexion, bending and rotation.
AB  - There is a paucity of data available for the moment arms of the muscles of the
      human neck. The objective of the present study was to measure the moment arms of
      the major cervical spine muscles in vitro. Experiments were performed on five
      fresh-frozen human head-neck specimens using a custom-designed robotic spine
      testing apparatus. The testing apparatus replicated flexion-extension, lateral
      bending and axial rotation of each individual intervertebral joint in the
      cervical spine while all other joints were kept immobile. The tendon excursion
      method was used to measure the moment arms of 30 muscle sub-regions involving 13
      major muscles of the neck about all three axes of rotation of each joint for the
      neutral position of the cervical spine. Significant differences in the moment arm
      were observed across sub-regions of individual muscles and across the
      intervertebral joints spanned by each muscle (p<0.05). Overall, muscle moment
      arms were larger in flexion-extension and lateral bending than in axial rotation,
      and most muscles had prominent moment arms in at least 2 out of the 3 joint
      motions investigated. This study emphasizes the importance of detailed
      representation of a muscle's architecture in prediction of its torque capacity
      about the individual joints of the cervical spine. The dataset produced may be
      useful in developing and validating computational models of the human neck.

PMID- 21074160
TI  - Quality of intertrochanteric cancellous bone as predictor of femoral stem RSA
      migration in cementless total hip arthroplasty.
AB  - In cementless total hip arthroplasty, osteoporosis may jeopardize the achievement
      of immediate stability and lead to migration of anatomically shaped femoral
      stems. Poor quality of proximal cancellous bone per se may also affect the rate
      of osseointegration. In a selected group of female total hip arthroplasty
      patients (mean age 64 years) with unremarkable medical history, intertrochanteric
      cancellous bone biopsy was taken from the site of stem implantation. Local bone
      quality, determined by structural MUCT imaging and destructive compression
      testing of the biopsy tissue, was used as the predictor of three-dimensional stem
      migration determined by radiostereometric analysis (RSA) up to 24 months. The
      patients exhibited major differences in mechanical properties of the
      intertrochanteric cancellous bone, which were closely related to the structural
      parameters calculated from MUCT data. Unexpectedly, the major differences
      observed in the quality of trochanteric cancellous bone had only minor
      reflections in the RSA migration of the femoral stems. In statistical analysis,
      the MUCT-based bone mineral density quartile (low, middle, high) was the only
      significant predictor for stem translation at 24 months (p=0.022) but only a
      small portion (R(2)=0.16) of the difference in translation could be explained by
      changes in bone mineral density quartile. None of the other parameters
      investigated predicted stem migration in translation or rotation. In conclusion,
      poor quality of intertrochanteric cancellous bone seems to contribute to the risk
      of implant migration less than expected. Probably also the importance of surgical
      preservation of intertrochanteric cancellous bone has been over-emphasized for
      osseointegration of cementless stem.

PMID- 21074161
TI  - Differences in whole-body angular momentum between below-knee amputees and non
      amputees across walking speeds.
AB  - Unilateral, below-knee amputees have an increased risk of falling compared to non
      amputees. The regulation of whole-body angular momentum is important for
      preventing falls, but little is known about how amputees regulate angular
      momentum during walking. This study analyzed three-dimensional, whole-body
      angular momentum at four walking speeds in 12 amputees and 10 non-amputees. The
      range of angular momentum in all planes significantly decreased with increasing
      walking speed for both groups. However, the range of frontal-plane angular
      momentum was greater in amputees compared to non-amputees at the first three
      walking speeds. This range was correlated with a reduced second vertical ground
      reaction force peak in both the intact and residual legs. In the sagittal plane,
      the amputee range of angular momentum in the first half of the residual leg gait
      cycle was significantly larger than in the non-amputees at the three highest
      speeds. In the second half of the gait cycle, the range of sagittal-plane angular
      momentum was significantly smaller in amputees compared to the non-amputees at
      all speeds. Correlation analyses suggested that the greater range of angular
      momentum in the first half of the amputee gait cycle is associated with reduced
      residual leg braking and that the smaller range of angular momentum in the second
      half of the gait cycle is associated with reduced residual leg propulsion. Thus,
      reducing residual leg braking appears to be a compensatory mechanism to help
      regulate sagittal-plane angular momentum over the gait cycle, but may lead to an
      increased risk of falling.

PMID- 21074162
TI  - Preparation and characterization of porous carbon material-coated solid-phase
      microextraction metal fibers.
AB  - Two kinds of porous carbon materials, including carbon aerogels (CAs), wormhole
      like mesoporous carbons (WMCs), were synthesized and used as the coatings of
      solid-phase microextraction (SPME) fibers. By using stainless steel wire as the
      supporting core, six types of fibers were prepared with sol-gel method, direct
      coating method and direct coating plus sol-gel method. Headspace SPME experiments
      indicated that the extraction efficiencies of the CA fibers are better than those
      of the WMC fibers, although the surface area of WMCs is much higher than that of
      CAs. The sol-gel-CA fiber (CA-A) exhibited excellent extraction properties for
      non-polar compounds (BTEX, benzene, toluene, ethylbenzene, o-xylene), while
      direct-coated CA fiber (CA-B) presented the best performance in extracting polar
      compounds (phenols). The two CA fibers showed wide linear ranges, low detection
      limits (0.008-0.047MUgL(-1) for BTEX, 0.15-5.7MUgL(-1) for phenols) and good
      repeatabilities (RSDs less than 4.6% for BTEX, and less than 9.5% for phenols)
      and satisfying reproducibilities between fibers (RSDs less than 5.2% for BTEX,
      and less than 9.9% for phenols). These fibers were successfully used for the
      analysis of water samples from the Pearl River, which demonstrated the
      applicability of the home-made CA fibers.

PMID- 21074163
TI  - Separation of phosphorylated peptides utilizing dual pH- and temperature
      responsive chromatography.
AB  - The phosphorylation of a peptide is considered to be one of the most important
      post-translational modification reactions that can alter protein function in
      mammalian cells. To separate and purify, we developed a dual temperature- and pH
      responsive chromatography based on terpolymer composed of N-isopropylacrylamide,
      N,N'-dimethylaminopropylacrylamide and butylmethacrylate. The property of the
      surface of the terpolymer-grafted stationary phase altered from hydrophilic to
      hydrophobic, and from changed to non-charged by changes in the temperature and
      the pH, respectively. In addition, it was possible to appear and hide ion
      exchange groups on the polymer chain surface by temperature changes. These
      phenomena resulted from changes in the charge and the hydrophobicity of the pH-
      and temperature-responsive polymer on the stationary surface by controlling the
      temperature. In the developed environmental-responsive chromatographic system,
      the ionizable dimethylamino group of N,N'-dimethylaminopropylacrylamide in
      terpolymer played a key role for the separation. We applied the developed
      chromatographic system to the separation of phosphorylated compounds, such as
      phospho-tyrosine, phosphopeptide and oligonucleotides. At a low column
      temperature, the electrostatic interaction plays a predominant role for retain
      anionic phosphorylated compounds, because of the strong interaction between the
      cationic dimethylamino group in the stationary phase and the anionic phosphoric
      group in the analyte. On the contrary, the hydrophobic interaction became
      predominant upon increasing the temperature. The results showed that both the
      electrostatic and the hydrophobic interactions became controllable with a
      temperature change during the chromatographic process. Dual pH- and temperature
      responsive chromatography would be very useful for biomacromolecules separation
      and purification.

PMID- 21074164
TI  - Loops, tails and trains: A simple model for structural transformations of grafted
      adsorbing neutral polymer brushes.
AB  - The structure of grafted adsorbing polymers on surfaces is described as a
      statistical ensemble of loops generated by an one-dimensional random walk
      perpendicular to the surface. The configuration of each chain is considered as a
      succession of closed loops ended by an open loop (a tail). The probability of
      formation of each individual loop is the product between the probability of first
      return to the surface and a Boltzmann factor containing the free energy of the
      Flory-Huggins kind, which is approximated by the minimum free energy of all
      possible configurations of that loop. At high grafting densities, the attractive
      interactions between monomers and surface control the fraction of polymer
      belonging to either closed loops or tails, hence the formation of a stretched
      grafted brush. At low grafting densities, the increase of that interaction above
      a critical value generates an abrupt collapse of the brush on the surface.
      Whereas for long polymers (with more than about 100 Kuhn segments), the structure
      of the brush can be determined, in general, only via Monte-Carlo sampling, it is
      argued that the two structural transitions indicated above can be well predicted
      by simple approximations.

PMID- 21074165
TI  - Synthesis of highly efficient C-doped TiO(2) photocatalyst and its photo
      generated charge-transfer properties.
AB  - Carbon-doped anatase TiO(2) was prepared by a facile hydrothermal process without
      adding additional carbon source. The as-prepared sample shows highly efficient
      photocatalytic activity, which only requires 4min and is about 11 times higher
      than that of Degussa P25 TiO(2) in degradation of methyl orange (MO) dye under UV
      light irradiation. Moreover, a highly visible-light activity is also observed. UV
      vis diffuse reflectance spectra and X-ray photoelectron spectroscopy confirm that
      the carbon atoms are incorporated into the interstitial positions of TiO(2)
      lattice and form a strong interaction with titanium atoms and extend
      photoresponding range to 700nm. Surface photovoltage spectra (SPS) and transient
      photovoltage (TPV) suggest that the presence of interstitial carbons induce
      several localized occupied states in the gap, enhance the separation extent and
      restrain the recombination of the photo-induced electron and hole carriers in
      TiO(2).

PMID- 21074166
TI  - Organic mediator-induced structural transformation in superlattices of monolayer
      protected gold nanoparticles.
AB  - N-acetylglutathione (NAG)-protected gold nanoparticles self-assemble into three
      dimensional (3D) face-centered cubic (fcc)-type superlattices at an air/water
      interface under highly acidic conditions. To prepare the well-defined
      superlattices, 1month's incubation is at least necessary since the size growth of
      the as-prepared nanoparticles is essential. Addition of 4-pyridinecarboxyic acid
      (PyC), a bifunctional hydrogen-bonding mediator, promotes the formation of the
      superlattices, which are created for about 2weeks' storage. Interestingly, PyC
      induced nanoparticle superlattices are in a body-centered tetragonal (bct)
      structure. The fcc-to-bct phase transformation would be due to stronger
      interaction between NAG and PyC than that between NAG molecules on the gold
      nanoparticle surfaces.

PMID- 21074167
TI  - Textural, structural, and morphological characterizations and catalytic activity
      of nanosized CeO(2)-MO(x) (M=Mg(2+), Al(3+), Si(4+)) mixed oxides for CO
      oxidation.
AB  - The present work focuses on the combination of ceria with another oxide of
      different ionic valences from period 3 (Mg(2+), Al(3+), and Si(4+)) using
      coprecipitation method, followed by calcination at 450 and 750 degrees C,
      respectively. The textural, structural, morphological and redox properties of
      nanosized ceria-magnesia, ceria-alumina and ceria-silica mixed oxides have been
      investigated by means of N(2) physisorption, XRD, Raman, HRTEM, DRS, FT-IR, and
      H(2)-TPR technologies. XRD results of these mixed oxides reveal that only
      nanocrystalline ceria (ca. 3-6nm for the 450 degrees C calcined samples) could be
      observed. The grain size of ceria increases with the increasing calcination
      temperature from 450 to 750 degrees C due to sintering effect. The highest
      specific surface area is obtained at CeO(2)-Al(2)O(3) mixed oxides when
      calcination temperature reaches 750 degrees C. Raman spectra display the cubic
      fluorite structure of ceria and the existence of oxygen vacancies, and
      displacement of oxygen ions from their normal lattice positions in the ceria
      based mixed oxides. DRS measurements confirm that the smaller the grain size of
      the ceria, the higher indirect band gap energy. H(2)-TPR results suggest that the
      reductions of surface and bulk oxygen of ceria were predominant at low and high
      calcination temperature, respectively. Finally, CO oxidation were performed over
      these ceria-based mixed oxides, and the combination of CeO(2)-Al(2)O(3) exhibited
      highest activity irrespective of calcination temperature, which may due to
      excellent textural/structural properties, good homogeneity, and redox abilities.

PMID- 21074168
TI  - An individual differences analysis of the self-teaching hypothesis.
AB  - The self-teaching hypothesis suggests that children learn orthographic structure
      of words through the experience of phonologically recoding them. The current
      study is an individual differences analysis of the self-teaching hypothesis. A
      total of 40 children in Grades 2 and 3 (7-9 years of age) completed tests of
      phonological recoding, word identification, and orthographic knowledge. The
      relation of phonological recoding and word identification was significantly
      mediated by orthographic knowledge. Furthermore, two aspects of orthographic
      knowledge (perhaps word-specific and general orthographic knowledge) mediated
      different variance shared between phonological recoding and word identification.
      Results support an individual differences version of the self-teaching hypothesis
      and emphasize the importance of phonological recoding in the primary curriculum.

PMID- 21074169
TI  - Developmental differences in children's context-dependent word learning.
AB  - In this study, 2.5-, 3-, and 4-year-olds (N=108) participated in a novel noun
      generalization task in which background context was manipulated. During the
      learning phase of each trial, children were presented with exemplars in one or
      multiple background contexts. At the test, children were asked to generalize to a
      novel exemplar in either the same or a different context. The 2.5-year-olds'
      performance was supported by matching contexts; otherwise, children in this age
      group demonstrated context dependent generalization. The 3-year-olds' performance
      was also supported by matching contexts; however, children in this age group were
      aided by training in multiple contexts as well. Finally, the 4-year-olds
      demonstrated high performance in all conditions. The results are discussed in
      terms of the relationship between word learning and memory processes; both
      general memory development and memory developments specific to word learning
      (e.g., retention of linguistic labels) are likely to support word learning and
      generalization.

PMID- 21074170
TI  - Symptomatic Chiari 1 malformation after initiation of growth hormone therapy.

PMID- 21074171
TI  - A near-miss: very long chain acyl-CoA dehydrogenase deficiency with normal
      primary markers in the initial well-timed newborn screening specimen.

PMID- 21074172
TI  - Interpreting conjugated bilirubin levels in newborns.
AB  - OBJECTIVE: To examine the clinical significance of elevated conjugated bilirubin
      (CB) levels in newborns. STUDY DESIGN: This retrospective study evaluated a birth
      cohort of 271 186 full-term newborns born within a Northern California hospital
      network from 1995 to 2004. All CB and direct bilirubin (DB) levels were available
      in a database and were correlated with the patients' inpatient and outpatient
      International Classification of Diseases, 9th Revision diagnoses. RESULTS: The
      99th percentile for CB is 0.5 mg/dL, and the 99th percentile for DB is 2.1 mg/dL.
      CB levels between 0.5 and 1.9 mg/dL can be associated with infection, but most
      often remain unexplained. Liver and biliary disease become increasingly likely as
      CB levels increase; for CB >=5 mg/dL, 47% of newborns have biliary disease and
      43% have liver disease. CONCLUSIONS: CB and DB levels are not interchangeable. In
      newborns with CB levels >=0.5 mg/dL and <2 mg/dL, infection must be ruled out,
      and the newborn should be observed. In newborns with levels >=2 mg/dL, a more in
      depth assessment of the hepatobiliary system is indicated.

PMID- 21074173
TI  - Low levels of asymmetric dimethylarginine in children with diabetes mellitus type
      I compared with healthy children.
AB  - OBJECTIVE: Although high levels of asymmetric dimethylarginine (ADMA) are
      associated with an increased risk for vasculopathy in adults, elevated ADMA
      concentrations also have been found in healthy young children. Patients with
      diabetes mellitus type 1 (DM1) are at risk for vasculopathy, and because the
      function of ADMA in the development of vascular symptoms is incompletely
      understood, we investigated ADMA concentrations in pediatric patients with DM1
      compared with healthy age- and sex-matched individuals. STUDY DESIGN: This cross
      sectional study included 85 pediatric patients with DM1 and 89 age- and sex
      matched healthy controls. RESULTS: ADMA concentrations were significantly lower
      in the patients with DM1 and were inversely correlated with hemoglobin A1c
      concentrations. CONCLUSIONS: Besides its vasoprotective function, nitric oxide
      itself may exert oxidative stress by generating free radicals. In these
      circumstances, ADMA would protect the system from nitric oxide overproduction and
      perpetuation of oxidative stress. This theory is supported by the physiologically
      higher ADMA concentrations in healthy children. Thus, low ADMA concentrations in
      children with DM1 may be an indicator of impaired protection against oxidative
      stress.

PMID- 21074174
TI  - Hypereosinophilic syndrome presenting as acute myocardial infarction in an
      adolescent.

PMID- 21074176
TI  - Preeclampsia, neutropenia, and risk of fungal sepsis in preterm very low birth
      weight infants.

PMID- 21074177
TI  - Green teeth.

PMID- 21074178
TI  - Does exposure to cats or dogs in early life alter a child's risk of atopic
      dermatitis?

PMID- 21074179
TI  - Is there a need to assess infant obesity at 6 months?

PMID- 21074180
TI  - Mental and behavioral health screening at preventive visits: opportunities for
      follow-up of patients who are nonadherent with the next preventive visit.
AB  - OBJECTIVES: To determine the type of subsequent care received by children
      nonadherent with their next preventive visit and whether behavioral factors
      predict use of emergency or acute care in this population. STUDY DESIGN: Data on
      1703 children (4-16 years) screened at a preventive visit with the Pediatric
      Symptom Checklist (PSC)/Youth-PSC were examined to determine subsequent
      preventive care adherence (10-18 months later). Then, nonadherent children were
      monitored to determine whether they returned to their medical home for acute
      care, delayed preventive care, or visited the emergency department (ED).
      Multivariate analyses were conducted to determine whether demographic and
      behavioral factors predicted return to either acute care or ED care site.
      RESULTS: Of the 461 children who were nonadherent with a second preventive care
      visit, most (85%) subsequently returned for acute, emergency, or delayed
      preventive care in the same medical system. Predictors of acute care or ED use
      included behavioral health risk characteristics (positive PSC, counseling,
      referral, parental concern), as well as adolescent age, self-pay and public
      insurance status, and living in lower socioeconomic communities. CONCLUSIONS:
      Pediatricians should consider acute care or ED visits as opportunities for mental
      health screening follow-up, and intervention in populations at high risk who miss
      preventive care.

PMID- 21074182
TI  - Surgical ligation for patent ductus arteriosus.

PMID- 21074183
TI  - Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and
      cervical adenitis syndrome.
AB  - We report three familial cases of periodic fever with aphthous stomatitis,
      pharyngitis, and cervical adenitis syndrome, including a pair of monozygotic
      twins and their mother. It suggests that periodic fever with aphthous stomatitis,
      pharyngitis, and cervical adenitis syndrome may have a certain monogenetic
      background.

PMID- 21074186
TI  - Regression in left ventricular mass after aortic valve replacement for chronic
      aortic regurgitation is unrelated to prosthetic valve size.
AB  - OBJECTIVES: We examined the role of prosthesis-patient mismatch on left
      ventricular mass regression after aortic valve replacement for chronic aortic
      valve regurgitation. METHODS: We selected patients who had complete preoperative
      and follow-up echocardiograms with measurement of left ventricular mass. Patients
      were excluded who had moderate or greater aortic valve stenosis, concomitant
      coronary artery bypass grafting, or mitral valve procedures. RESULTS: Patients'
      mean age was 55 +/- 17 years; 21% were female. The mean preoperative indexed left
      ventricular mass was 150 +/- 45 g/m(2). Patients with mildly (n = 44; mean
      indexed mass, 126 +/- 15 g/m(2)), moderately (n = 31; mean indexed mass, 168 +/-
      11 g/m(2)), or severely (n = 15; mean indexed mass, 241 +/- 34 g/m(2)) increased
      preoperative indexed left ventricular mass, were similar, except for lower
      ejection fractions, larger end-diastolic dimensions, and larger ventricular wall
      thicknesses in the severely enlarged group (P < .001). Thirteen patients had
      prosthesis-patient mismatch and were similar to patients without prosthesis
      patient mismatch, except for a greater body surface area, fewer mechanical
      valves, and smaller valve sizes in those with prosthesis-patient mismatch (P <
      .05). At a mean follow-up of 3.2 +/- 2.4 years, the average reduction in indexed
      left ventricular mass was 50 +/- 38 g/m(2); late mass regression was unrelated to
      labeled valve size, prosthesis-patient mismatch, or measured indexed effective
      aortic valve area. A greater preoperative indexed left ventricular mass (P <
      .001) was an independent predictor of greater left ventricular mass regression.
      Despite having greater left ventricular mass regression, patients with severe
      preoperative indexed left ventricular mass did not return to normal values (mean,
      142 +/- 25 g/m(2)). CONCLUSIONS: Left ventricular mass regression after aortic
      valve replacement for chronic aortic regurgitation is unrelated to indexed
      prosthetic valve area. Although incomplete, regression is greatest in patients
      with the largest preoperative indexed left ventricular mass.

PMID- 21074187
TI  - Safety and efficacy of pericardial endoscopy by percutaneous subxyphoid approach
      in swine heart in vivo.
AB  - OBJECTIVE: A nonsurgical approach from the epicardial surface is useful for
      various cardiac interventions, such as positioning of the left ventricular lead
      for cardiac resynchronization therapy and epicardial ablation. Stem cell delivery
      on the epicardial surface can be considered in the future if good quality of
      visualization can be obtained. However, because the pericardial space is limited,
      hemodynamic conditions may deteriorate with pericardial endoscopy. Therefore, the
      feasibility and efficacy of pericardial endoscopy were examined by using ready
      made endoscopes. METHODS: Anesthetized swines (26-61 kg; n = 6) were used for the
      experiment. Electrocardiogram, femoral artery blood pressure, and oxygen
      saturation by pulse oximetry were continuously monitored during the procedures.
      Guided by the fluoroscopy, sheaths were advanced to the pericardial space using
      the modified Seldinger technique from the subxyphoid space. RESULTS: After
      insertion of an endoscope with a maximum diameter of 6.9 mm, hemodynamic
      parameters were stable during the procedure with atropine. Stable and acceptable
      endoscopic images were obtained. Minor operations can be performed with
      pericardial endoscopic-guided laparoscopic forceps with no complications.
      CONCLUSIONS: The endoscopic pericardial procedure is effective and feasible. This
      procedure can increase the possibility and efficacy of nonsurgical treatment for
      cardiac diseases.

PMID- 21074188
TI  - Totally thoracoscopic resection of a superior mediastinal tumor extending above
      the thoracic inlet.

PMID- 21074189
TI  - Simulation and skills training in mitral valve surgery.
AB  - OBJECTIVE: Limited exposure and visualization and technical complexity have
      affected resident training in mitral valve surgery. We propose simulation-based
      learning to improve skill acquisition in mitral valve surgery. METHODS: After
      reviewing instructional video recordings of mitral annuloplasty in porcine and
      plastic models, 11 residents (6 integrated and 5 traditional) performed porcine
      model mitral annuloplasty. Video-recorded performance was reviewed by attending
      surgeon providing audio formative feedback superimposed on video recordings;
      recordings were returned to residents for review. After 3-week practice with
      plastic model, residents repeated porcine model mitral annuloplasty. Performance
      assessments initially (prefeedback) and at 3 weeks (postfeedback) were based on
      review of video recordings on 5-point rating scale (5, good; 3, average; 1, poor)
      of 11 components. Ratings were averaged for composite score. RESULTS: Time to
      completion improved from mean 31 +/- 9 minutes to 25 +/- 6 minutes after 3-week
      practice (P = .03). At 3 weeks, improvement in technical components was achieved
      by all residents, with prefeedback scores varying from 2.4 +/- 0.6 for needle
      angles to 3.0 +/- 0.5 for depth of bites and postfeedback scores of 3.1 +/- 0.8
      for tissue handling to 3.6 +/- 0.8 for suture management and tension (P <= .001).
      Interrater reliability was greater than 0.8. In this sample, composite scores of
      first-year integrated and traditional residents were lower than those of senior
      level residents; comparatively, third-year integrated residents demonstrated good
      technical proficiency. CONCLUSIONS: Simulation-based learning with formative
      feedback results in overall improved performance of simulated mitral
      annuloplasty. In complex surgical procedures, simulation may provide necessary
      early graduated training and practice. Importantly, a "passing" grade can be
      established for proficiency-based advancement.

PMID- 21074190
TI  - Apicoaortic conduit in a patient with severe aortic stenosis: an alternative to
      transcutaneous aortic valve implantation.

PMID- 21074191
TI  - Tumor volume threshold of insignificant prostate cancer--was Dr. Stamey right all
      along?

PMID- 21074192
TI  - Treatment of muscle invasive bladder cancer: evidence from the National Cancer
      Database, 2003 to 2007.
AB  - PURPOSE: We describe nationwide treatment patterns of muscle invasive bladder
      cancer, investigated determinants of cystectomy and provide contemporary trends
      in process of care measures in patients undergoing cystectomy. MATERIALS AND
      METHODS: We selected 40,388 patients 18 to 99 years old diagnosed with muscle
      invasive (stages II to IV) bladder cancer in 2003 to 2007 from the National
      Cancer Database. Treatment included cystectomy, neoadjuvant and adjuvant
      chemotherapy, chemotherapy without surgery and radiation therapy. In patients
      undergoing cystectomy we retrieved the procedure type (partial vs radical),
      lymphadenectomy extent and 30-day followup. Cystectomy determinants were assessed
      by Poisson regression with robust error variance. Perioperative mortality was
      analyzed by multilevel logistic regression. RESULTS: The proportion of patients
      treated with cystectomy (42.9%) and radiation therapy (16.6%) remained stable
      with time while the incidence of those who received chemotherapy increased from
      27.0% in 2003 to 34.5% in 2007 due to an increase in neoadjuvant chemotherapy and
      chemotherapy without surgery. The cystectomy rate decreased with age and was
      lower in racial/ethnic minorities (especially black patients), uninsured or
      Medicaid patients, patients residing in the South and Northeast, and those
      treated at nonteaching/research hospitals. The partial cystectomy rate decreased
      and lymphadenectomy extent increased with time. The perioperative mortality rate
      was 2.6% and it was higher at low vs very high volume hospitals (OR 1.71, 95% CI
      1.26-2.32). CONCLUSIONS: Recent nationwide data confirm ongoing improvements in
      process of care measures in patients who undergo cystectomy but also show marked
      differences in treatment patterns for muscle invasive bladder cancer by patient
      age, race, insurance status, geographic area and facility type.

PMID- 21074194
TI  - Recommendations for post-prostatectomy radiation therapy in the United States
      before and after the presentation of randomized trials.
AB  - PURPOSE: The EORTC 22911 and the SWOG 8794 studies, presented in 2004 and 2005,
      showed that adjuvant radiation therapy after prostatectomy improved biochemical
      disease-free survival in men with adverse pathological features. In this study we
      evaluated the use of post-prostatectomy radiation therapy following the
      presentation of these results, and the impact of margin involvement, pathological
      tumor stage, Gleason score and sociodemographic factors on post-prostatectomy
      radiation therapy recommendations. MATERIALS AND METHODS: The SEER cancer
      registry was used to identify 21,917 men who underwent radical prostatectomy for
      N0M0 prostate cancer with adverse pathological features (pT3 or margin positive
      pT2 disease) from 2000 through 2007. RESULTS: After adjusting for age, diagnosis
      year, race, SEER region and county education level in a multivariable regression
      model, decreasing age, margin involvement and Gleason 8 to 10 cancer were
      associated with receiving post-prostatectomy radiation therapy (all p < 0.001).
      Men with pT3a (AOR 2.95, CI 2.64-3.29) and pT3b disease (AOR 6.77, CI 5.75-7.97)
      were more likely to receive post-prostatectomy radiation therapy than those with
      pT2 disease. The use of post-prostatectomy radiation therapy did not increase
      after the presentation of study results (p = 0.166). CONCLUSIONS: While men with
      involved margins and more aggressive pathological disease features were more
      likely to receive post-prostatectomy radiation therapy, recommendations for post
      prostatectomy radiation did not increase after the initial reports from the
      randomized trials, perhaps because these studies initially reported improved
      biochemical disease-free survival but not overall survival. Whether the recent
      report of a survival benefit from adjuvant radiation therapy in the SWOG trial
      will impact patterns of care requires further followup.

PMID- 21074193
TI  - Prospective evaluation of operating characteristics of prostate cancer detection
      biomarkers.
AB  - PURPOSE: We assessed the independent predictive values of the serum markers free
      prostate specific antigen, proenzyme prostate specific antigen, neuroendocrine
      marker and Dickkopf-1 compared to serum prostate specific antigen and other
      standard risk factors for early prostate cancer detection. MATERIALS AND METHODS:
      From the prospectively collected SABOR cohort 250 prostate cancer cases, and 250
      mean age matched and proportion of African-American race/ethnicity matched
      controls were selected who had a prior available prostate specific antigen and
      digital rectal examination. Serum samples were obtained, and free prostate
      specific antigen, [-2]proenzyme prostate specific antigen, Dickkopf-1 and
      neuroendocrine marker were measured. AUC, sensitivities and specificities were
      calculated, and multivariable logistic regression was used to assess the
      independent predictive value compared to prostate specific antigen, digital
      rectal examination, family history, prior biopsy history, race/ethnicity and age.
      RESULTS: The AUCs (95% CI) were 0.76 (0.71, 0.8) for free prostate specific
      antigen, 0.72 (0.67, 0.76) for [-2]proenzyme prostate specific antigen, 0.76
      (0.72, 0.8) for %free prostate specific antigen, 0.61 (0.56, 0.66) for %[
      2]proenzyme prostate specific antigen, 0.73 (0.68, 0.77) for prostate health
      index, 0.53 (0.48, 0.58) for Dickkopf-1 and 0.53 (0.48, 0.59) for neuroendocrine
      marker. In the 2 to 10 ng/ml prostate specific antigen range the AUCs (95% CI)
      were 0.58 (0.49, 0.67) for free prostate specific antigen, 0.53 (0.44, 0.62) for
      [-2]proenzyme prostate specific antigen, 0.67 (0.59, 0.75) for %free prostate
      specific antigen, 0.57 (0.49, 0.65) for %[-2]proenzyme prostate specific antigen
      and 0.59 (0.51, 0.67) for phi. Only %free prostate specific antigen retained
      independent predictive value compared to the traditional risk factors.
      CONCLUSIONS: Free prostate specific antigen retained independent diagnostic
      usefulness for prostate cancers detected through prostate specific antigen and
      digital rectal examination screening. Prostate specific antigen isoforms are
      highly correlated with prostate specific antigen. Future research is needed to
      identify new markers associated with prostate cancer through different
      mechanisms.

PMID- 21074195
TI  - Transcription factor E3 and transcription factor EB renal cell carcinomas:
      clinical features, biological behavior and prognostic factors.
AB  - PURPOSE: Translocation renal cell carcinomas represent a distinct
      clinicopathological entity. Studying the natural history, biological behavior and
      potential prognostic factors are crucially warranted. MATERIALS AND METHODS: We
      selected 54 patients with renal cell carcinoma with positive nuclear
      transcription factor E3 and transcription factor EB expression from the Juvenile
      RCC Network. Recurrence-free survival and overall survival were assessed.
      RESULTS: Median patient age was 24 years (range 1 to 64) and the male-to-female
      ratio was 1:1.4. At diagnosis 35 patients (65%) had local disease while 19 (35%)
      presented with distant metastases. The latter patients were older (median age 36
      years) and predominantly male (male-to-female ratio 2) whereas the former group
      had a median age of 16 years and a male-to-female ratio of 1:2.5. Overall 36
      patients underwent complete tumor resection and of these 8 had recurring cancer.
      On univariate analysis only lymph node involvement and American Joint Committee
      on Cancer stage were associated with poor recurrence-free survival. When
      stratified according to lymph node status age 25 years or older was found to
      predict relapse (p = 0.03). With a median followup of 19.2 months (range 1 to 58)
      3-year overall survival was 14.3% in patients with distant metastasis and 70.6%
      in those without distant metastasis. Distant metastasis developed in the 2
      patients with ASPSCR1-TFE3 fusion vs 1 of 11 with other fusion genes.
      CONCLUSIONS: Transcription factor E3 and transcription factor EB renal cell
      carcinoma display different clinical behavior according to gender and age. Lymph
      node involvement represents the only factor that predicts recurrence. ASPSCR1
      TFE3 might be the most aggressive among the transcription factor E3 fusion genes.

PMID- 21074196
TI  - Prognostic impact of muscular venous branch invasion in localized renal cell
      carcinoma cases.
AB  - PURPOSE: Beginning with the 2002 American Joint Committee on Cancer staging
      system, renal sinus muscular venous branch invasion has prognostic equivalence
      with renal vein invasion in renal cell carcinoma cases. To validate this presumed
      equivalence we compared patients with isolated muscular venous branch invasion to
      those with renal vein invasion and those with no confirmed vascular invasion.
      MATERIALS AND METHODS: From routine cataloging at our institution we identified
      500 patients who underwent partial or radical nephrectomy from 2003 to 2008.
      After excluding patients with metastasis or noncortical renal cell carcinoma
      pathology we identified 85 with positive muscular venous branch invasion (+). The
      259 patients with pT1-2 muscular venous branch (-) invasion and the 71 with renal
      vein (+) invasion served as comparison groups. We used a multivariate Cox model
      to control for tumor characteristics using the Kattan renal cell carcinoma
      nomogram. RESULTS: On multivariate analysis the risk of recurrence in the pT1-2
      muscular venous branch invasion (-) group was lower than in the muscular venous
      branch invasion (+) group (HR 0.06, 95% CI 0.02-0.18, p < 0.001). Patients with
      renal vein invasion (+) had a recurrence rate similar to that in those with
      muscular venous branch invasion (+) (HR 0.80, 95% CI 0.39-1.65, p = 0.6). The
      overall survival rate was higher in the muscular venous branch invasion (-) group
      than in the other groups. CONCLUSIONS: Patients with muscular venous branch
      invasion have an outcome inferior to that in patients with pT1-2 disease. This
      confirms the adverse prognosis of muscular venous branch invasion and supports
      pathological up-staging. The prognosis of muscular venous branch invasion is
      similar to that of renal vein invasion, although we cannot exclude the
      possibility of a difference. Our findings underscore the importance of close
      patient followup and careful pathological assessment of the nephrectomy specimen.

PMID- 21074197
TI  - An outbreak of achromobacter xylosoxidans associated with ultrasound gel used
      during transrectal ultrasound guided prostate biopsy.
AB  - PURPOSE: We describe an outbreak of Achromobacter xylosoxidans after transrectal
      ultrasound guided prostate biopsy at a urology unit at a tertiary care center as
      well as clinical and microbiological investigation, and intervention. MATERIALS
      AND METHODS: In September 2008, several days after undergoing transrectal
      ultrasound guided prostate biopsy, 4 patients were hospitalized with fever. We
      reviewed the procedure and infection control practices in the urology service.
      Environmental cultures were obtained from equipment and materials used for the
      procedure. Isolates were identified by routine laboratory procedures with
      molecular confirmation and characterized by pulsed field gel electrophoresis.
      RESULTS: A. xylosoxidans was isolated from the urine of 2 patients, of whom 1
      also had a positive blood culture. Review of transrectal ultrasound guided
      prostate biopsy revealed that the lubricant gel used in the procedure, which the
      biopsy needle passes through, was held in a plastic container that was repeatedly
      refilled from a large bag. A. xylosoxidans was isolated from this container.
      Pulsed field gel electrophoresis showed that the isolates obtained from patients
      and the gel were identical. CONCLUSIONS: Contaminated lubricant gel was the cause
      of this outbreak. The practice of repeatedly refilling gel containers with
      nonsterile gel was replaced by the use of individual sterile gel sachets in each
      patient. No further cases occurred. During an invasive procedure involving a
      sterile body site, such as transrectal ultrasound guided prostate biopsy, using
      sterile gel is essential. Our experience emphasizes the crucial need to review
      all invasive procedures from an infection control perspective.

PMID- 21074198
TI  - Comparative effectiveness of perineal versus retropubic and minimally invasive
      radical prostatectomy.
AB  - PURPOSE: While perineal radical prostatectomy has been largely supplanted by
      retropubic and minimally invasive radical prostatectomy, it was the predominant
      surgical approach for prostate cancer for many years. In our population based
      study we compared the use and outcomes of perineal radical prostatectomy vs
      retropubic and minimally invasive radical prostatectomy. MATERIALS AND METHODS:
      We identified men diagnosed with prostate cancer from 2003 to 2005 who underwent
      perineal (452), minimally invasive (1,938) and retropubic (6,899) radical
      prostatectomy using Surveillance, Epidemiology and End Results-Medicare linked
      data through 2007. We compared postoperative 30-day and anastomotic stricture
      complications, incontinence and erectile dysfunction, and cancer therapy
      (hormonal therapy and/or radiotherapy). RESULTS: Perineal radical prostatectomy
      comprised 4.9% of radical prostatectomies during our study period and use
      decreased with time. On propensity score adjusted analysis men who underwent
      perineal vs retropubic radical prostatectomy had shorter hospitalization (median
      2 vs 3 days, p < 0.001), received fewer heterologous transfusions (7.2% vs 20.8%,
      p < 0.001) and required less additional cancer therapy (4.9% vs 6.9%, p = 0.020).
      When comparing perineal vs minimally invasive radical prostatectomy men who
      underwent the former required more heterologous transfusions (7.2% vs 2.7%, p =
      0.018) but experienced fewer miscellaneous medical complications (5.3% vs 10.0%,
      p = 0.045) and erectile dysfunction procedures (1.4 vs 2.3/100 person-years, p =
      0.008). The mean and median expenditure for perineal radical prostatectomy in the
      first 6 months postoperatively was $1,500 less than for retropubic or minimally
      invasive radical prostatectomy (p < 0.001). CONCLUSIONS: Men who undergo perineal
      vs retropubic and minimally invasive radical prostatectomy experienced favorable
      outcomes associated with lower expenditure. Urologists may be abandoning an
      underused but cost-effective surgical approach that compares favorably with its
      successors.

PMID- 21074199
TI  - Determining factors for hospital discharge status after radical cystectomy in a
      large contemporary cohort.
AB  - PURPOSE: We describe hospital discharge status in patients after radical
      cystectomy for bladder cancer. We determined factors affecting discharge status.
      MATERIALS AND METHODS: The 445 patients underwent radical cystectomy for
      urothelial carcinoma from January 2004 to December 2007. Patients were grouped by
      hospital discharge status into 1 of 4 groups, including home under self-care
      without services, home with home health services, subacute, rehabilitation or
      skilled nursing facility, or hospice/in-hospital mortality. We compared clinical,
      perioperative and pathological variables in these groups. We also examined the
      association of discharge status with the hospital readmission rate and 90-day
      mortality. RESULTS: Of the 440 patients 250 (56.8%), 145 (32.9%), 39 (8.9%) and 6
      (1.4%) were in the home without services, home with services, facility and
      mortality groups, respectively. On multivariate analysis older age, lower
      preoperative albumin, unmarried status and higher Charlson comorbidity index were
      predictors of discharge home with services while older age, poor preoperative
      exercise tolerance and longer hospital stay predicted discharge to a facility.
      Patients in the facility group were more likely to die within 90 days of surgery
      than those who returned home independently or with services. There was no
      difference in the likelihood of rehospitalization. CONCLUSIONS: Sociodemographic
      factors, preoperative performance status, and comorbidities and perioperative
      factors contribute to the discharge decision after radical cystectomy. Some
      subgroups can be predicted to have increased postoperative care needs and may be
      appropriate targets for disposition planning preoperatively.

PMID- 21074200
TI  - Editorial comment.

PMID- 21074201
TI  - The impact of cytoreductive nephrectomy on survival of patients with metastatic
      renal cell carcinoma receiving vascular endothelial growth factor targeted
      therapy.
AB  - PURPOSE: Vascular endothelial growth factor targeted therapy is a standard of
      care in patients with metastatic renal cell carcinoma. The role of cytoreductive
      nephrectomy in the era of novel agents remains poorly defined. MATERIALS AND
      METHODS: We retrospectively reviewed baseline characteristics and outcomes of 314
      patients with anti-vascular endothelial growth factor therapy naive, metastatic
      renal cell carcinoma from United States and Canadian cancer centers to study the
      impact of cytoreductive nephrectomy on overall survival. RESULTS: Patients who
      underwent cytoreductive nephrectomy (201) were younger (p < 0.01), and more
      likely to have a better Karnofsky performance status (p < 0.01), more than 1 site
      of metastasis (p = 0.04) and lower corrected calcium levels (p < 0.01) compared
      to those who did not undergo cytoreductive nephrectomy (113). On univariable
      analysis cytoreductive nephrectomy was associated with a median overall survival
      of 19.8 months compared to 9.4 months for patients who did not undergo
      cytoreductive nephrectomy (HR 0.44; 95% CI 0.32, 0.59; p < 0.01). On
      multivariable analysis and adjusting for established prognostic risk factors the
      overall survival difference persisted (adjusted HR 0.68; 95% CI 0.46, 0.99; p =
      0.04) in favor of the cytoreductive nephrectomy group. In subgroup analyses
      stratified for favorable/intermediate/poor risk criteria, patients in the poor
      risk group had a marginal benefit (p = 0.06). Similarly patients with Karnofsky
      performance status less than 80% also had a marginal survival benefit (p = 0.08).
      CONCLUSIONS: In this retrospective study cytoreductive nephrectomy was
      independently associated with a prolonged overall survival of patients with
      metastatic renal cell carcinoma treated with vascular endothelial growth factor
      targeted agents, although the benefit is marginal in those patients with poor
      risk features.

PMID- 21074203
TI  - Laparoscopic cryoablation for a 3 cm nonhilar renal tumor.

PMID- 21074202
TI  - Usefulness of the Spanish Urological Club for Oncological Treatment scoring model
      to predict nonmuscle invasive bladder cancer recurrence in patients treated with
      intravesical bacillus Calmette-Guerin plus interferon-alpha.
AB  - PURPOSE: The Spanish Urological Club for Oncological Treatment recently developed
      a scoring model to stratify the recurrence risk in patients treated with
      intravesical bacillus Calmette-Guerin using gender, age, grade, tumor status, T
      category, multiplicity and associated carcinoma in situ. We investigated the
      ability of this model to stratify the recurrence risk in patients with nonmuscle
      invasive bladder cancer undergoing combination bacillus Calmette-Guerin plus
      interferon alpha-2B therapy. MATERIALS AND METHODS: We retrospectively reviewed
      data from a national multicenter phase II trial of bacillus Calmette-Guerin plus
      interferon alpha-2B in patients with nonmuscle invasive bladder cancer to
      identify 718 with the data required to use the model. Recurrence was defined as
      visible tumor on cystoscopy unless histologically confirmed as benign, definitive
      positive cytology or biopsy proven disease even with negative cystoscopy. Time to
      recurrence was indexed to the first intravesical treatment date. Patients were
      assigned points based on the model and then divided into 4 groups based on total
      score, including 0 to 4, 5 or 6, 7 to 9 and 10 or greater. RESULTS: The model
      successfully stratified the recurrence risk into 4 statistically different groups
      based on score with a 3-year recurrence-free rate of 58%, 52%, 42% and 26% for
      scores of 0 to 4, 5 or 6, 7 to 9 and 10 or greater, respectively (p < 0.001).
      CONCLUSIONS: The Spanish Urological Club for Oncological Treatment scoring model
      is a useful prognostic tool to stratify recurrence risk in patients with
      nonmuscle invasive bladder cancer who are treated with combined intravesical
      bacillus Calmette-Guerin plus interferon alpha-2B. Larger, prospective trials are
      required for full model validation.

PMID- 21074204
TI  - No good options.

PMID- 21074205
TI  - Chronic kidney disease before and after partial nephrectomy.
AB  - PURPOSE: We performed a multi-institutional retrospective cohort study to
      evaluate baseline renal function of patients who underwent partial nephrectomy
      for renal tumors, and determined rates of progression to higher stages of chronic
      kidney disease. MATERIALS AND METHODS: The Modification of Diet in Renal Disease
      study equation was used to estimate glomerular filtration rate. Preoperative and
      postoperative serum creatinine values were obtained from patients who underwent
      partial nephrectomy at 6 institutions with a normal contralateral kidney, and had
      baseline chronic kidney disease stage I (estimated glomerular filtration rate
      greater than 90 ml/minute/1.73 m(2)), II (estimated glomerular filtration rate 60
      to 89 ml/minute/1.73 m(2)) or III (estimated glomerular filtration rate 30 to 59
      ml/minute/1.73 m(2)). The end point was change in chronic kidney disease stage at
      long-term followup (3 to 18 months). Multivariate logistic and Cox regression
      models tested the association of newly acquired chronic kidney disease stage III
      or greater with pertinent demographic, tumor and surgical factors. RESULTS: For
      1,228 patients with followup creatinine data at least 3 months after partial
      nephrectomy median baseline glomerular filtration rate was 74 ml/minute/1.73
      m(2). At baseline 19%, 59% and 22% of patients had chronic kidney disease stage
      I, II and III, respectively. At long-term followup for patients with baseline
      chronic kidney disease stage I or II median postoperative glomerular filtration
      rate was 67 ml/minute/1.73 m(2) with 29% having progression to chronic kidney
      disease stage III or greater. Increasing age, female gender, increasing tumor
      size, clamping of the renal artery and vein, and lower preoperative estimated
      glomerular filtration rate were independently associated with newly acquired
      chronic kidney disease stage III or greater. The presence of comorbid conditions
      such as coronary artery disease, diabetes mellitus or hypertension did not
      independently predict an increased risk of higher chronic kidney disease stage.
      CONCLUSIONS: Chronic kidney disease stage III or greater will develop
      postoperatively in approximately a third of patients with an estimated glomerular
      filtration rate greater than 60 ml/minute/1.73 m(2), and this progression is
      associated with definable demographic, tumor and surgical factors.

PMID- 21074207
TI  - Rational use of desmopressin in adults.

PMID- 21074206
TI  - Feasibility and outcomes of partial nephrectomy for resection of at least 20
      tumors in a single renal unit.
AB  - PURPOSE: Patients with hereditary renal cancer are at increased risk for
      recurrent bilateral multifocal tumors and may require aggressive nephron sparing
      surgery to prevent renal replacement therapy. We evaluated feasibility and
      outcomes in patients who underwent partial nephrectomy with removal of at least
      20 tumors in a single renal unit at 1 setting. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 30 patients who underwent a total of 34
      partial nephrectomies with removal of at least 20 tumors at our institution from
      1993 to 2008. Operative reports and hospital records were reviewed for
      perioperative data, and renal functional and oncologic outcomes. We compared
      preoperative and postoperative renal function with the 2-tailed t test. RESULTS:
      There were no deaths and only 1 renal unit was lost. A median of 26.5 tumors was
      removed. Median estimated blood loss was 3,500 ml and median operative time was 9
      hours. Perioperative complications developed in greater than 50% of cases. There
      was a statistically significant decrease in the estimated glomerular filtration
      rate at 3 months (67 vs 59 ml/minute/1.73 m(2), p < 0.001). Only 1 patient had
      metastatic disease. Eight of the 34 operated kidneys required subsequent
      intervention during the median followup of 52 months (range 4 to 187).
      CONCLUSIONS: Aggressive partial nephrectomy to resect multiple tumors is
      technically feasible. There was a significant decrease in postoperative renal
      function but more than 80% of preoperative renal function was preserved in this
      cohort except in 1 patient. Also, oncologic outcomes were encouraging at
      intermediate term followup.

PMID- 21074208
TI  - A biosensor platform for rapid antimicrobial susceptibility testing directly from
      clinical samples.
AB  - PURPOSE: A significant barrier to efficient antibiotic management of infection is
      that the standard diagnostic methodologies do not provide results at the point of
      care. The delays between sample collection and bacterial culture and antibiotic
      susceptibility reporting have led to empirical use of antibiotics, contributing
      to the emergence of drug resistant pathogens. As a key step toward the
      development of a point of care device for determining the antibiotic
      susceptibility of urinary tract pathogens, we report on a biosensor based
      antimicrobial susceptibility test. MATERIALS AND METHODS: For assay development
      bacteria were cultured with or without antibiotics, and growth was quantitated by
      determining viable counts and electrochemical biosensor measurement of bacterial
      16S rRNA. To determine antibiotic susceptibility directly from patient samples,
      urine was cultured on antibiotic plates for 2.5 hours and growth was determined
      by electrochemical measurement of bacterial 16S rRNA. For assay validation 252
      urine samples were collected from patients at the Spinal Cord Injury Service at
      Veterans Affairs Palo Alto Health Care System. The biosensor based antimicrobial
      susceptibility test was completed for samples containing gram-negative organisms.
      Pathogen identification and antibiotic susceptibility results were compared
      between our assay and standard microbiological analysis. RESULTS: A direct
      biosensor quantitation of bacterial 16S rRNA can be used to monitor bacterial
      growth for a biosensor based antimicrobial susceptibility test. Clinical
      validation of a biosensor based antimicrobial susceptibility test with patient
      urine samples demonstrated that this test was 94% accurate in 368 pathogen
      antibiotic tests compared to standard microbiological analysis. CONCLUSIONS: This
      biosensor based antimicrobial susceptibility test, in concert with our previously
      described pathogen identification assay, can provide culture and susceptibility
      information directly from a urine sample within 3.5 hours.

PMID- 21074209
TI  - Editorial comment.

PMID- 21074210
TI  - Pathological, immunohistochemical and cytogenetic features of papillary renal
      cell carcinoma with clear cell features.
AB  - PURPOSE: Papillary renal cell carcinoma is characterized histologically by tumors
      with cells arranged in a papillary pattern. Typically the cells have a
      chromophilic appearance but areas may show cells with clear cytoplasm, similar to
      those in clear cell renal cell carcinoma. MATERIALS AND METHODS: We re-reviewed
      the histological slides of 148 patients with papillary renal cell carcinoma who
      underwent nephrectomy for the presence of clear cells. Results were correlated
      with other pathological features, immunohistochemical expression of 22 protein
      markers, cytogenetic analysis and overall survival. RESULTS: Papillary renal cell
      carcinoma with clear cells was identified in 57 patients (39%). Clear cells were
      associated with higher T classification and grade, vascular invasion and type 2
      papillary renal cell carcinoma. On immunohistochemistry these tumors revealed
      higher expression of epithelial vascular endothelial growth factor receptor-2
      than papillary renal cell carcinoma without clear cells. All papillary renal cell
      carcinomas with clear cells expressed alpha-methylacyl-coenzyme A racemase and
      76% expressed cytokeratin 7. Six of 8 tumors (75%) with chromosome 3p loss had
      clear cell features. The presence of clear cells was retained as an independent
      prognostic factor on multivariate analysis. In cases of papillary renal cell
      carcinoma with clear cells the loss of 3p material and absent cytokeratin 7
      expression were associated with a worse outcome. CONCLUSIONS: Papillary renal
      cell carcinoma with clear cells is a novel entity with a unique clinical,
      immunohistochemical and cytogenetic phenotype. The presence of clear cells is
      associated with aggressive pathological characteristics and poorer prognosis.

PMID- 21074211
TI  - Prostate cancer in men 70 years old or older, indolent or aggressive:
      clinicopathological analysis and outcomes.
AB  - PURPOSE: Currently there is a lack of consensus on screening recommendations for
      prostate cancer with minimal guidance on the cessation of screening in older men.
      We defined the clinicopathological features and outcomes for men 70 years old or
      older who were diagnosed with prostate cancer. MATERIALS AND METHODS: The Center
      for Prostate Disease Research database was queried for all men diagnosed with
      prostate cancer from 1989 to 2009. The patients were stratified into age
      quartiles and by race. Cox proportional hazard models were used to compare
      clinicopathological features across patient stratifications. Kaplan-Meier
      analysis was used to compare biochemical recurrence-free, prostate cancer
      specific and overall survival. RESULTS: Of the 12,081 men evaluated 3,650 (30.2%)
      were 70 years old or older. These men had a statistically significant higher
      clinical stage, biopsy grade and prediagnosis prostate specific antigen velocity
      (p < 0.0001). For those patients who underwent prostatectomy, pathological stage,
      grade and surgical margin status were all significantly higher in men 70 years
      old or older. Biochemical recurrence and secondary treatment were also more
      common in this age group (p < 0.0001). Multivariate analysis revealed age 70
      years or older as a significant predictor of biochemical recurrence after
      prostatectomy (HR 1.45, p = 0.0054). Overall survival was lowest in men age 70
      years or older who had surgery, but interestingly the mean time to death was
      comparable regardless of age. CONCLUSIONS: Our findings indicate that as men age,
      parameters consistent with more aggressive disease become more prevalent. The
      etiology of this trend is unknown. However, these data may have implications for
      current screening and treatment recommendations.

PMID- 21074212
TI  - A critical analysis of the tumor volume threshold for clinically insignificant
      prostate cancer using a data set of a randomized screening trial.
AB  - PURPOSE: The identification of clinically insignificant prostate cancer could
      help avoid overtreatment. Current criteria for insignificant prostate cancer use
      a tumor volume threshold of less than 0.5 ml for the index tumor. In this study
      we reassess this tumor volume threshold for clinically insignificant prostate
      cancer using an independent data set. MATERIALS AND METHODS: The rate of
      insignificant prostate cancer was calculated by modeling lifetime risk estimates
      of prostate cancer diagnosis in screened and nonscreened participants in a
      randomized prostate cancer screening trial. Using lifetime risk estimates 50.8%
      of screen detected prostate cancer was calculated to be clinically insignificant
      and the 49.2% largest tumor volume of 325 prostatectomy specimens was used to
      determine the threshold tumor volume for insignificant prostate cancer. Because
      stage and grade represent the strongest determinants of cancer aggressiveness, we
      also calculated the tumor volume threshold for insignificant cancer after the
      selection of patients with organ confined prostate cancer without Gleason pattern
      4/5. The analyses were performed for total tumor volume and for index tumor
      volume. RESULTS: The minimum threshold tumor volume of the index tumor and total
      tumor was 0.55 and 0.70 ml, respectively. After accounting for tumor stage and
      grade we obtained a threshold volume for the index tumor and total tumor of 1.3
      and 2.5 ml, respectively. CONCLUSIONS: We confirmed the original value of the
      index tumor volume threshold of 0.5 ml for insignificant prostate cancer, and we
      demonstrated that clinically insignificant prostate cancer may include index
      Gleason score 6, pT2 tumors with volumes up to at least 1.3 ml. These results
      suggest a reconsideration of current methods and nomograms used for pretreatment
      risk assessment.

PMID- 21074213
TI  - Editorial comment.

PMID- 21074214
TI  - The effect of dutasteride on the usefulness of prostate specific antigen for the
      diagnosis of high grade and clinically relevant prostate cancer in men with a
      previous negative biopsy: results from the REDUCE study.
AB  - PURPOSE: We assessed whether dutasteride enhances the usefulness of total
      prostate specific antigen for diagnosing clinically significant prostate cancer.
      MATERIALS AND METHODS: The 4-year REDUCE study evaluated the efficacy and safety
      of 0.5 mg dutasteride daily for prostate cancer risk reduction in men with a
      prostate specific antigen of 2.5 to 10.0 ng/ml and a negative prostate biopsy.
      Specificity, sensitivity, and positive and negative predictive values of prostate
      specific antigen for the diagnosis of prostate cancer were assessed. RESULTS:
      Final prostate specific antigen before biopsy and change from month 6 to final
      prostate specific antigen performed better for the diagnosis of Gleason score 7
      10 tumors in men who received dutasteride vs placebo as assessed by the area
      under the ROC curves (0.700 vs 0.650, p = 0.0491; and 0.699 vs 0.593, p = 0.0001,
      respectively). Increases in prostate specific antigen were associated with a
      higher likelihood of biopsy detectable, Gleason score 7-10 and clinically
      significant (modified Epstein criteria) prostate cancer. Percentage decreases in
      prostate specific antigen from baseline to month 6 in the dutasteride arm did not
      predict prostate cancer overall or Gleason score 7-10 cancer. CONCLUSIONS: In men
      with a previously negative prostate biopsy, prostate specific antigen performed
      better during the 4-year study as a marker of prostate cancer in men who received
      dutasteride vs placebo. The degree of prostate specific antigen increase after 6
      months was a better indicator of clinically significant cancer in the dutasteride
      arm than in the placebo arm. Conversely, the initial decrease in prostate
      specific antigen in men taking dutasteride did not predict the likelihood of
      prostate cancer.

PMID- 21074215
TI  - Role of estrogen in normal male function: clinical implications for patients with
      prostate cancer on androgen deprivation therapy.
AB  - PURPOSE: Patients with prostate cancer on androgen deprivation therapy with
      luteinizing hormone-releasing hormone agonists experience deleterious side
      effects, including sexual dysfunction, hot flashes and osteoporosis. Estrogen may
      relieve or reduce some of these side effects. We explore the role of estrogen in
      normal male function, emphasizing sexual interest and performance. MATERIALS AND
      METHODS: We reviewed the literature on androgen deprivation therapy, estrogen and
      sexual function in males using PubMed(r) and other sources. RESULTS: Estrogen
      receptors are present in tissues involved in sexual behavior including several
      brain centers and pelvic floor muscles. Exogenous estrogens can restore some
      sexual interest to greater than castrate level in castrated animals. This has
      also been reported for certain androgen deprived patients (eg voluntarily
      castrated men, male-to-female transsexuals) who take exogenous estrogens and
      others who are on high dose antiandrogens which increase endogenous estradiol
      levels. Estrogen also helps prevent hot flashes and bone mineral loss, which
      commonly occur with luteinizing hormone-releasing hormone agonist treatment.
      However, estrogen may cause gynecomastia and increases the risk of breast cancer.
      Thus, patients with prostate cancer should be informed about the pros and cons of
      estrogen therapy before starting androgen deprivation therapy. Based on these
      data estrogen is likely to have maximal benefits in men if initiated
      simultaneously with androgen deprivation therapy. Because estrogen autoregulates
      its own receptors, a constant dose of estrogen will not likely produce a constant
      serum concentration, suggesting that its effectiveness could be optimized if
      administered cyclically. CONCLUSIONS: Prospective studies on the ability of
      parenteral estrogen to preserve sexual interest at greater than castrate level in
      patients with prostate cancer are warranted.

PMID- 21074216
TI  - [Multidrug-resistant spinal tuberculosis and giant paraspinal abscesses].

PMID- 21074217
TI  - [Takayasu's arteritis: infrequent or underdiagnosed?].

PMID- 21074218
TI  - [About discharge clinical reports].

PMID- 21074219
TI  - [Response to rituximab in two patients with plasma exchange-refractory thrombotic
      thrombocytopenic purpura].

PMID- 21074220
TI  - [Expected effects of specific ions versus real effects of their intake from a
      bottled water].

PMID- 21074221
TI  - [Massive destructive sinusitis following cocaine inhalation].

PMID- 21074222
TI  - [Fulminating hepatitis for imatinib in a patient with chronic myeloid leukaemia].

PMID- 21074223
TI  - [Meropenem decreases valproate plasmatic concentrations].

PMID- 21074224
TI  - [Rapidly growing cutaneous lesion in the left shoulder].

PMID- 21074225
TI  - [Prognostic value of NT-proBNP in heart failure with preserved ejection
      fraction].

PMID- 21074226
TI  - [Rosai-Dorfman disease mimicking meningiomatosis: a case report].
AB  - Rosai-Dorfman disease (RDD), also known as sinus histocytosis with massive
      lymphadenopathy, is a rare idiopathic histioproliferative disease affecting the
      lymph nodes. Although extranodal involvement has been reported in diverse sites,
      central nervous system manifestations, particularly in the absence of nodal
      disease with clinical and radiological findings suggestive of meningioma, are
      extremely rare. Histopathology and immunohistochemistry are essential for a
      positive diagnosis. We report a case of RDD in a patient presenting multiple
      meningeal nodules with a review of the literature and discussion of differential
      diagnosis.

PMID- 21074228
TI  - Tei index (myocardial performance index) and cardiac biomarkers in dogs with
      parvoviral enteritis.
AB  - Tei index (myocardial performance) and cardiac biomarkers were evaluated in dogs
      with parvoviral enteritis (PVE). Tei index was calculated as isovolumic
      contraction time plus isovolumic relaxation time divided by ejection time.
      Myocardial and skeletal muscle damages were assessed by serum levels of cardiac
      troponin I (cTnI), creatine (phospho) kinase, lactate dehydrogenase and aspartate
      aminotransferase. Serum magnesium level was also determined. According to
      treatment response, dogs were divided into the survivor (n=20) and non-survivor
      groups (n=23). Seven healthy dogs served as controls. The mean value of the Tei
      index was higher in non-survivors, compared with survivors (p<0.02) and healthy
      controls (p<0.01). Serum level of cTnI in non-survivors was higher than that of
      survivors and controls (p<0.05). Tei index showed the highest sensitivity and
      specificity to predict mortality. The findings of an elevated Tei index and an
      increase in serum cTnI are factors associated with a poor prognosis in cases of
      canine parvovirosis.

PMID- 21074227
TI  - Comparative study of the plasma globulin level, CD21(-) B-cell counts and FOXP3
      mRNA expression level in CD4(+) T-cells for different clinical stages of feline
      immunodeficiency virus infected cats.
AB  - Feline immunodeficiency virus (FIV) infection leads to hypergammaglobulinemia
      through mechanisms that remain poorly understood. We investigated changes in
      plasma globulin level, B cells, and T cells with progression of the clinical
      stage of FIV-infected cats. We classified FIV-infected cats into the stage of
      Asymptomatic carrier (AC) and AIDS-related complex (ARC) based on the clinical
      symptoms, and measured the plasma globulin level, the CD4(+) T-cell counts, and
      analyzed surface markers of B cells. We investigated the relationship between the
      plasma globulin level and regulatory T cells (Tregs) using the Forkhead box P3
      (FOXP3) mRNA expression level. In FIV-infected cats, the plasma globulin level
      and the surface immunoglobulin (sIg)(+) CD21(-) B-cell counts were increased,
      whereas the CD4(+) T-cell counts were decreased compared with specific-pathogen
      free (SPF) cats. The mRNA expression of Blimp-1 (master gene of plasma cells) was
      increased in peripheral blood, and the FOXP3 mRNA expression level was decreased
      in CD4(+) T-cells. These immunological changes were marked in the ARC stage.
      These data indicate that the decrease of Tregs and the increase of plasma cells
      lead to hypergammaglobulinemia.

PMID- 21074229
TI  - Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in
      clinically affected gnotobiotic pigs.
AB  - Porcine circovirus type 2 (PCV2) is clinically associated with respiratory
      disease, failure-to-thrive, hepatitis, and diarrhea; however, the precise
      pathogenesis of PCV2-associated disease and in particular its involvement in
      apoptosis is still controversial. The objectives of this study were (1) to
      determine whether PCV2 is associated with apoptosis by examining and comparing
      hepatic tissues from clinically affected or unaffected gnotobiotic pigs that were
      experimentally infected with PCV2, (2) to determine if there are differences
      between PCV2a and PCV2b in inducing hepatocyte apoptosis, and (3) to determine if
      there are differences between apoptosis detection systems. Forty-eight
      gnotobiotic pigs were separated into five groups based on inoculation status and
      development of clinical disease: (1) sham-inoculated, clinically-unaffected
      (n=4), (2) inoculated with PCV2a, clinically-unaffected (n=10), (3) inoculated
      with PCV2a, clinically-affected (n=6), (4) inoculated with PCV2b, clinically
      unaffected, (n=13) and (5) inoculated with PCV2b, clinically-affected (n=15).
      Formalin-fixed, paraffin-embedded sections of liver from all pigs were analyzed
      for signs of apoptosis [presence of single strand DNA breaks in the nucleus by
      the terminal transferase dUTP nick end labeling (TUNEL) assay or presence of
      intra-nuclear cleaved caspase 3 (CCasp3) demonstrated by CCasp3
      immunohistochemistry (IHC)]. In addition, the liver tissues were also tested for
      presence of cytoplasmic and intra-nuclear PCV2 antigen by an IHC assay. Specific
      CCasp3 and TUNEL labeling was detected in the nucleus of hepatocytes in PCV2a and
      PCV2b infected pigs with significantly (P<0.05) higher levels of apoptotic cells
      in clinically-affected pigs. Regardless of PCV2 subtype (PCV2a; PCV2b), there
      were higher levels of PCV2 antigen in clinically-affected pigs compared to
      clinically-unaffected pigs. There was no significant difference in detection rate
      of apoptotic cells between the TUNEL assay and CCasp3 IHC. When high amounts of
      PCV2 antigen were present, the incidence of CCasp3 and TUNEL staining also
      increased regardless of the PCV2 genotype. This suggests that PCV2-induced
      apoptosis of hepatocytes is important in the pathogenesis of PCV2-associated
      lesions and disease.

PMID- 21074230
TI  - The relationship between serum biotin and oxidant/antioxidant activities in
      bovine lameness.
AB  - Serum biotin concentrations, erythrocyte superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and plasma
      thiobarbituric acid reactive substances (TBARS) were measured in 36 dairy cows,
      18 of them were healthy and served as control. In the 18 cows with lameness
      problems, there were 5 cows with interdigital necrobacillosis, 5 cows with
      subsolar abscessation, 2 cows with solar ulcers, 2 cows with white line disease,
      2 cows with chronic laminitis and 2 cows with septic arthritis. The degree of
      lameness was estimated to be slight in 3 cows, moderate in 11 cows and severe in
      4 cows. Plasma fibrinogen levels and TBARS concentrations were increased
      significantly (P<=0.05) in lame cows compared to control group. The antioxidant
      enzymes GSH-Px, and CAT concentrations were increased significantly (P<=0.05) in
      lame cows. The level of reduced glutathione and the activity of SOD were
      significantly decreased in affected cows compared to healthy ones. Serum biotin
      levels in healthy cows ranged from 2.25 to 3.5ng/ml while in lame cows, biotin
      levels ranged from 1.17 to 2.3ng/ml. Biotin levels correlated positively with
      blood GSH (r=0.870, P<=0.05), (r=0.735, P<=0.05) and with GSH-Px (r=0.539,
      P<=0.05), (r=0.637, P<=0.05) and with SOD (r=0.637, P<=0.05), (r=0.449, P<=0.05)
      and with catalase (r=0.533, P<=0.05), (r=0.585, P<=0.05) in both healthy and
      lameness affected subjects, respectively.

PMID- 21074231
TI  - California mastitis test scores as indicators of subclinical intra-mammary
      infections at the end of lactation in dairy cows.
AB  - Intramammary infections (IMI) during the dry period can be reduced through the
      use of dry cow therapy (DCT); in the future, its blanket use is likely to be
      questioned in the light of public concern regarding the routine use of
      antibiotics in food producing animals. One possible alternative is to limit DCT
      to cows with IMI just before drying off, which would require a quick, simple
      identification of sub-clinical IMI. In the present study we examined quarter milk
      samples obtained from 240 cows one week before and on the day of drying off,
      using the California mastitis test (CMT) and for IMI by bacteriological culture.
      The results indicated that high CMT scores at drying off may be good indicators
      of IMI: there was a significant association between the frequency of isolation of
      major pathogens and the CMT score in milk samples obtained one week before
      (Pearson's chi(2)=27.04, df=4, p<0.001) and those at drying off (Pearson's
      chi(2)=25.87, df=4, p<0.001).

PMID- 21074232
TI  - Molecular epidemiology of bluetongue virus serotype 1 isolated in 2006 from
      Algeria.
AB  - This study reports on an outbreak of disease that occurred in central Algeria
      during July 2006. Sheep in the affected area presented clinical signs typical of
      bluetongue (BT) disease. A total of 5245 sheep in the affected region were
      considered to be susceptible, with 263 cases and thirty-six deaths. Bluetongue
      virus (BTV) serotype 1 was isolated and identified as the causative agent.
      Segments 2, 7 and 10 of this virus were sequenced and compared with other
      isolates from Morocco, Italy, Portugal and France showing that they all belong to
      a 'western' BTV group/topotype and collectively represent a western Mediterranean
      lineage of BTV-1.

PMID- 21074233
TI  - Diagnosis of visceral leishmaniasis.
AB  - Leishmaniasis is a vector-borne disease with up to 350 million people at risk of
      infection worldwide. Among its different clinical manifestations, visceral is the
      most severe form. Since clinical features of visceral leishmaniasis (VL) mimic
      several other common diseases, accurate diagnosis is crucial as the treatment is
      associated with significant toxicity. Invasive and risky techniques involving
      demonstration of the parasites in stained preparations from splenic and bone
      marrow aspirate is still the gold standard for VL diagnosis. Serological tests
      using rK39 in ELISA or rapid immunochromatographic format, Direct Agglutination
      Test (DAT), immunoblotting have issues related to a significant proportion of
      asymptomatic individuals being positive with these tests and their inability to
      diagnose relapses as these remain positive for several months to years after
      cure. PCR is the most common molecular technique successfully used for diagnosis
      and differentiation of species. Through this review we focus extensively on the
      comparative utilities of the various diagnostic tools currently available for VL,
      describing in depth their advantages and disadvantages, addressing the recent
      advances attained in the field. A simple, rapid, non invasive, accurate and cost
      effective marker of active VL, which can be used in field conditions, is
      necessary to improve diagnosis of VL.

PMID- 21074234
TI  - The N-terminal region of the human papillomavirus L2 protein contains overlapping
      binding sites for neutralizing, cross-neutralizing and non-neutralizing
      antibodies.
AB  - The N-terminal region of the human papillomavirus (HPV) L2 protein has been shown
      to contain immune epitopes able to induce the production of neutralizing and
      cross-neutralizing antibodies (Gambhira et al., 2007; Kawana et al., 1999). Using
      bacterial thioredoxin as a scaffold, we managed to enhance the immunogenicity of
      putative L2 neutralizing epitopes, but only a minor fraction of the resulting
      immune responses was found to be neutralizing (Rubio et al., 2009). To determine
      the recognition patterns for non-neutralizing, neutralizing and cross
      neutralizing antibodies, we isolated and characterized a panel of 46 monoclonal
      antibodies directed against different HPV16 L2 epitopes. Four of such antibodies
      proved to be neutralizing, and two of them, both targeting the amino acid (aa) 20
      38 region of L2, were found to cross-neutralize a broad range of
      papillomaviruses. The epitopes recognized by neutralizing and cross-neutralizing
      antibodies were mapped at high resolution and were found to be characterized by
      distinct recognition patterns. Even in the case of the L2 20-38 epitope, cross
      neutralization of HPV31 pseudovirions proved to be extremely inefficient, and
      this was found to be primarily due to the lack of a proline residue at position
      30. HPV16 specific amino acids in this region also appear to be responsible for
      the lack of cross-neutralizing activity, thus suggesting a potential immune
      escape mechanism. For the aa 71-80 region, instead, the data indicate that
      restriction of neutralization to HPV16 is due to sequence (or structural)
      differences laying outside of the epitope. Besides providing new insights on the
      molecular bases of L2-mediated immune reactivity, the present data may pave the
      way to novel vaccination approaches specifically evoking cross-neutralizing
      antibody responses.

PMID- 21074235
TI  - Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2
      polymerase gene evaluated in mouse and pig models.
AB  - PB2 627K is a determinant of influenza host range and contributes to the
      pathogenicity of human-, avian-, and mouse-adapted influenza viruses in the mouse
      model. Here we used mouse and pig models to analyze the contribution of a swine
      origin and avian-origin PB2 carrying either 627K or 627E in the background of the
      classical swine H1N1 (A/Swine/Iowa/15/30; 1930) virus. The results showed PB2
      627K is crucial for virulence in the mouse model, independent of whether PB2 is
      derived from an avian or swine influenza virus (SIV). In the pig model, PB2 627E
      decreases pathogenicity of the classical 1930 SIV when it contains the swine
      origin PB2, but not when it possesses the avian-origin PB2. Our study suggests
      the pathogenicity of SIVs with different PB2 genes and mutation of codon 627 in
      mice does not correlate with the pathogenicity of the same SIVs in the natural
      host, the pig.

PMID- 21074236
TI  - Evaluation of pepper mild mottle virus, human picobirnavirus and Torque teno
      virus as indicators of fecal contamination in river water.
AB  - A reliable indicator is needed to predict and reduce the risk of infection
      associated with fecal contamination of surface water. Since Pepper mild mottle
      virus (PMMoV), human picobirnaviruses (hPBV) and Torque teno virus (TTV) have
      been detected at substantial levels in human feces, we explored whether detection
      of nucleic acids of these viruses is a suitable indicator of fecal contamination
      in river water. From September 2008 to December 2009, water samples (n = 111)
      were collected from the Ruhr and Rhine rivers and from the influents and
      effluents of a wastewater plant (n = 12). Quantitative real time (RT-) PCR was
      used to determine the abundance of PMMoV, hPBV, and TTV in comparison to human
      adenoviruses (HAdV) and human polyomaviruses (HPyV) that are frequently detected
      in surface water and were previously proposed as indicators. While PMMoV was
      detected in all river water samples, the other viruses were detected less
      frequently. The concentration of the studied viruses in positive river water
      ranged from 5 * 10(1) to 1.07 * 10(6) genome equivalents per liter (gen.equ./l).
      All wastewater samples were positive for PMMoV, HAdV and HPyV, while TTV and hPBV
      were detected in 6/12 and 3/12 of samples, respectively. To determine if PMMoV is
      specific to human-derived fecal waste, fecal samples from human (n = 20) and
      animal (n = 53) were also tested. In contrast to the ubiquity of PMMoV in human
      feces (19/20) the virus was only detected at low concentration in a minority of
      the animal fecal samples tested (7/15 from chicken, 1/10 from Geese and 1/6 from
      cows). Therefore, in this setting TTV and hPBV do not seem to be suitable
      indicators of fecal contamination in water. Whereas, the high excretion level and
      dissemination of PMMoV in human sewage and river water suggest that PMMoV could
      be a promising indicator of fecal pollution in surface water.

PMID- 21074237
TI  - Rotating disk electrodes to assess river biofilm thickness and elasticity.
AB  - The present study examined the relevance of an electrochemical method based on a
      rotating disk electrode (RDE) to assess river biofilm thickness and elasticity.
      An in situ colonisation experiment in the River Garonne (France) in August 2009
      sought to obtain natural river biofilms exhibiting differentiated architecture. A
      constricted pipe providing two contrasted flow conditions (about 0.1 and 0.45 m
      s(-1) in inflow and constricted sections respectively) and containing 24 RDE was
      immersed in the river for 21 days. Biofilm thickness and elasticity were
      quantified using an electrochemical assay on 7 and 21 days old RDE-grown biofilms
      (t(7) and t(21), respectively). Biofilm thickness was affected by colonisation
      length and flow conditions and ranged from 36 +/- 15 MUm (mean +/- standard
      deviation, n = 6) in the fast flow section at t(7) to 340 +/- 140 MUm (n = 3) in
      the slow flow section at t(21). Comparing the electrochemical signal to
      stereomicroscopic estimates of biofilms thickness indicated that the method
      consistently allowed (i) to detect early biofilm colonisation in the river and
      (ii) to measure biofilm thickness of up to a few hundred MUm. Biofilm elasticity,
      i.e. biofilm squeeze by hydrodynamic constraint, was significantly higher in the
      slow (1300 +/- 480 MUm rpm(1/2), n = 8) than in the fast flow sections (790 +/-
      350 MUm rpm(1/2), n = 11). Diatom and bacterial density, and biofilm-covered RDE
      surface analyses (i) confirmed that microbial accrual resulted in biofilm
      formation on the RDE surface, and (ii) indicated that thickness and elasticity
      represent useful integrative parameters of biofilm architecture that could be
      measured on natural river assemblages using the proposed electrochemical method.

PMID- 21074238
TI  - Influence of sampling strategies on the monitoring of cyanobacteria in shallow
      lakes: lessons from a case study in France.
AB  - Sampling cyanobacteria in freshwater ecosystems is a crucial aspect of monitoring
      programs in both basic and applied research. Despite this, few papers have dealt
      with this aspect, and a high proportion of cyanobacteria monitoring programs are
      still based on monthly or twice-monthly water sampling, usually performed at a
      single location. In this study, we conducted high frequency spatial and temporal
      water sampling in a small eutrophic shallow lake that experiences cyanobacterial
      blooms every year. We demonstrate that the spatial and temporal aspects of the
      sampling strategy had a considerable impact on the findings of cyanobacteria
      monitoring in this lake. In particular, two peaks of Aphanizomenon flos-aquae
      cell abundances were usually not picked up by the various temporal sampling
      strategies tested. In contrast, sampling once a month was sufficient to provide a
      good overall estimation of the population dynamics of Microcystis aeruginosa. The
      spatial frequency of sampling was also important, and the choice in the location
      of the sampling points around the lake was very important if only two or three
      sampling points were used. When four or five sampling points were used, this
      reduced the impact of the choice of the location of the sampling points, and
      allowed to obtain fairly similar results than when six sampling points were used.
      These findings demonstrate the importance of the sampling strategy in
      cyanobacteria monitoring, and the fact that it is impossible to propose a single
      universal sampling strategy that is appropriate for all freshwater ecosystems and
      also for all cyanobacteria.

PMID- 21074239
TI  - Crystal structures of native and inactivated cis-3-chloroacrylic acid
      dehalogenase: Implications for the catalytic and inactivation mechanisms.
AB  - The isomeric mixture of cis- and trans-1,3-dichloropropene constitutes the active
      component of a widely used nematocide known as Telone II(r). The mixture is
      processed by various soil bacteria to acetaldehyde through the 1,3
      dichloropropene catabolic pathway. The pathway relies on an isomer-specific
      hydrolytic dehalogenation reaction catalyzed by cis- or trans-3-chloroacrylic
      acid dehalogenase, known respectively as cis-CaaD and CaaD. Previous sequence
      analysis and crystallographic studies of the native and covalently modified
      enzymes identified Pro-1, His-28, Arg-70, Arg-73, Tyr-103, and Glu-114 as key
      binding and catalytic residues in cis-CaaD. Mutagenesis of these residues
      confirmed their importance to the dehalogenation reaction. Crystal structures of
      the native enzyme (2.01A resolution) and the enzyme covalently modified at the
      Pro-1 nitrogen by 2-hydroxypropanoate (1.65A resolution) are reported here. Both
      structures are at a resolution higher than previously reported (2.75A and 2.1A
      resolution, respectively). The conformation of the covalent adduct is strikingly
      different from that previously reported due to its interaction with a 7-residue
      loop (Thr-32 to Leu-38). The participation of another active site residue, Arg
      117, in catalysis and inactivation was also examined. The implications of the
      combined findings for the mechanisms of catalysis and inactivation are discussed.

PMID- 21074240
TI  - Investigation of arsenic accumulation and tolerance potential of Sesuvium
      portulacastrum (L.) L.
AB  - Sesuvium portulacastrum (L.) L., a facultative halophyte, is considered a
      suitable candidate for the phytoremediation of metals. An investigation of As
      accumulation and tolerance was conducted in Sesuvium plants upon exposure to
      As(V) (100-1000 MUM) for 30 d. Plants demonstrated a good growth even after
      prolonged exposure (30 d) to high As(V) concentrations (1000 MUM) and a
      significant As accumulation (155 MUg g-1 dry weight) with a bioaccumulation
      factor of more than ten at each concentration. The results of shoot and root dry
      weight, malondialdehyde accumulation, photosynthetic pigments, and total soluble
      proteins demonstrated that plants did not experience significant toxicity even at
      1000 MUM As(V) after 30 d. However, metabolites (total non-protein thiols and
      cysteine) and enzymes (serine acetyltransferase, cysteine synthase and gamma
      glutamylcysteine synthetase) of thiol metabolism, in general, remained either
      unaffected or showed slight decline. Hence, plants tolerated high As(V)
      concentrations without an involvement of thiol metabolism as a major component.
      Taken together, the results indicate that plants are potential As accumulator and
      may find application in the re-vegetation of As contaminated sites.

PMID- 21074241
TI  - The toxicity of titanium dioxide nanopowder to early life stages of the Japanese
      medaka (Oryzias latipes).
AB  - In this study, fertilized Japanese medaka (Oryzias latipes) embryos were exposed
      from fertilization to 5 d post-hatch using static non-renewal assays to aqueous
      suspensions of titanium dioxide nanoparticles (nTiO2) ranging in nominal
      concentrations between 0 and 14 MUg mL-1. The average size of the nTiO2 in the
      stock solution before addition to the test treatments was 87 nm (+/-14 nm). TiO2
      materials accumulated in a concentration dependent manner on the chorionic
      filaments of developing medaka embryos with evidence of pericardial edema
      occurring during embryo development. However, no significant (p > 0.05) increases
      in mortality relative to control treatments were observed for the nTiO2 exposed
      embryos. A concentration dependent increase in cumulative percent hatch was
      observed at 11 d, indicating that exposure to increasing concentrations of nTiO2
      resulted in the premature hatch of medaka embryos. Post-hatch, a significant
      proportion of sac fry from the nTiO2 exposure groups exhibited moribund swimming
      behavior and these individuals also experienced greater mortality at 15 d post
      hatch. Combined, these results demonstrate that exposure to nTiO2 can impact the
      development of early life stages of fish.

PMID- 21074242
TI  - The differentially-expressed proteome in Zn/Cd hyperaccumulator Arabis paniculata
      Franch. in response to Zn and Cd.
AB  - The Zn/Cd hyperaccumulator Arabis paniculata is able to tolerate high level of Zn
      and Cd. To clarify the molecular basis of Zn and Cd tolerance, proteomic
      approaches were applied to identify proteins involved in Zn and Cd stress
      response in A. paniculata. Plants were exposed to both low and high Zn or Cd
      levels for 10 d. Proteins of leaves in each treatment were separated by 2-DE (two
      dimensional electrophoresis). Nineteen differentially-expressed proteins upon Zn
      treatments and 18 proteins upon Cd treatments were observed. Seventeen out of 19
      of Zn-responsive proteins and 16 out of 18 of Cd-responsive proteins were
      identified using MALDI-TOF/TOF-MS (matrix-assisted laser desorption/ionization
      time of flight mass spectrometry). The most of identified proteins were known to
      function in energy metabolism, xenobiotic/antioxidant defense, cellular
      metabolism, protein metabolism, suggesting the responses of A. paniculata to Zn
      and Cd share similar pathway to certain extend. However, the different metal
      defense was also revealed between Zn and Cd treatment in A. paniculata. These
      results indicated that A. paniculata against to Zn stress mainly by enhancement
      of energy metabolism including auxin biosynthesis and protein metabolism to
      maintain plant growth and correct misfolded proteins. In the case of Cd, plants
      adopted antioxidative/xenobiotic defense and cellular metabolism to keep cellular
      redox homeostasis and metal-transportation under Cd stress.

PMID- 21074243
TI  - Importance of sulfate reducing bacteria in mercury methylation and demethylation
      in periphyton from Bolivian Amazon region.
AB  - Sulfate reducing bacteria (SRB) are important mercury methylators in sediments,
      but information on mercury methylators in other compartments is ambiguous. To
      investigate SRB involvement in methylation in Amazonian periphyton, the
      relationship between Hg methylation potential and SRB (Desulfobacteraceae,
      Desulfobulbaceae and Desulfovibrionaceae) abundance in Eichhornia crassipes and
      Polygonum densiflorum root associated periphyton was examined. Periphyton
      subsamples of each macrophyte were amended with electron donors (lactate, acetate
      and propionate) or inhibitors (molybdate) of sulfate reduction to create
      differences in SRB subgroup abundance, which was measured by quantitative real
      time PCR with primers specific for the 16S rRNA gene. Mercury methylation and
      demethylation potentials were determined by a stable isotope tracer technique
      using 200HgCl and CH3(202)HgCl, respectively. Relative abundance of
      Desulfobacteraceae (<0.01-12.5%) and Desulfovibrionaceae (0.01-6.8%) were both
      highly variable among samples and subsamples, but a significant linear
      relationship (p<0.05) was found between Desulfobacteraceae abundance and net
      methylmercury formation among treatments of the same macrophyte periphyton and
      among all P. densiflorum samples, suggesting that Desulfobacteraceae bacteria are
      the most important mercury methylators among SRB families. Yet, molybdate only
      partially inhibited mercury methylation potentials, suggesting the involvement of
      other microorganisms as well. The response of net methylmercury production to the
      different electron donors and molybdate was highly variable (3-1104 pg g(-1) in
      12 h) among samples, as was the net formation in control samples (17-164 pg g(-1)
      in 12 h). This demonstrates the importance of community variability and
      complexity of microbial interactions for the overall methylmercury production in
      periphyton and their response to external stimulus.

PMID- 21074244
TI  - Development of solid phase adsorption toxin tracking (SPATT) for monitoring
      anatoxin-a and homoanatoxin-a in river water.
AB  - Sampling and monitoring for cyanotoxins can be problematic as concentrations
      change with environmental and hydrological conditions. Current sampling practices
      (e.g. grab samples) provide data on cyanotoxins present only at one point in time
      and may miss areas or times of highest risk. Recent research has identified the
      widespread distribution of anatoxin-producing benthic cyanobacteria in rivers
      highlighting the need for development of effective sampling techniques. In this
      study we evaluated the potential of an in situ method known as solid phase
      adsorption toxin tracking (SPATT) for collecting and concentrating anatoxin-a
      (ATX) and homoanatoxin-a (HTX) in river water. Fifteen different adsorption
      substrates were screened for efficiency of ATX uptake, nine of which retained
      high proportions (>70%) of ATX. Four substrates were then selected for a 24-h
      trial in a SPATT bag format in the laboratory. The greatest decrease in ATX in
      the water was observed with powdered activated carbon (PAC) and Strata-X (a
      polymeric resin) SPATT bags. A 3-d field study in a river containing toxic
      benthic cyanobacterial mats was undertaken using PAC and Strata-X SPATT bags. ATX
      and HTX were detected in all SPATT bags. Surface grab samples were taken
      throughout the field study and ATX and HTX were only detected in one of the water
      samples, highlighting the limitations of this currently used method. Both Strata
      X and PAC were found to be effective absorbent substrates. PAC has the advantage
      that it is cheap and readily available and appears to continue to sorb toxins
      over longer periods than Strata-X. SPATT has the potential to be integrated into
      current cyanobacterial monitoring programmes and would be a very useful and
      economical tool for early warning of ATX and HTX contamination in water.

PMID- 21074245
TI  - Residues and dynamics of pymetrozine in rice field ecosystem.
AB  - The fate of pymetrozine was studied in rice field ecosystem, and a simple and
      reliable analytical method for determination of pymetrozine in soil, rice straw,
      paddy water and brown rice was developed. Pymetrozine residues were extracted
      from samples, cleaned up by solid phase extraction (SPE) and then determined by
      high-performance liquid chromatography electrospray ionization tandem mass
      spectrometry (LC-ESI-MS-MS). The average recovery was 81.2-88.1% from soil, 83.4
      88.6% from rice straw, 87.3-94.1% from paddy water and 82.9-85.3% from brown
      rice. The relative standard deviation (RSD) was less than 15%. The limits of
      detection (LODs) of pymetrozine calculated as a sample concentration were 0.0003
      mg kg(-1) (mg L(-1)) for soil and paddy water, 0.001 mg kg(-1) for brown rice and
      rice straw. The results of kinetics study of pymetrozine residue showed that
      pymetrozine degradation in water, soil, and rice straw coincided with C=0.194e(
      0.986t), C=0.044e(-0.099t), and C=0.988e(-0.780t), respectively; the half-lives
      were about 0.70 d, 7.0 d and 0.89 d, respectively. The degradation rate of
      pymetrozine in water was the fastest, followed by rice straw. The highest final
      pymetrozine residues in brown rice were 0.01 mg kg(-1), which was lower than the
      EU's upper limit of 0.02 mg kg(-1) in rice. Therefore, a dosage of 300-600 g
      a.i.hm(-2) was recommended, which could be considered as safe to human beings and
      animals.

PMID- 21074246
TI  - The effect of waste combustion on the occurrence of polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated
      biphenyls (PCBs) in breast milk in Italy.
AB  - Levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated
      dibenzofurans (PCDFs) were measured in the breast milk of mothers living in
      Giugliano (Campania, Italy), an area at increased risk of PCDD and PCDF exposure
      caused by recent and serious open-air waste-combustion accidents. Polychlorinated
      biphenyls (PCBs) in milk samples were also studied. Breast milk was also
      monitored in two cities in northern Italy, Milan and Piacenza, which were
      selected as controls. Other variables, such as diet and age of the mothers, were
      also studied. PCDD/F and PCB levels and congener profiles in breast-milk samples
      were similar in all these cities, though total PCDD/F and DL-PCB TEQs in samples
      from Giugliano were significantly lower than those in Milan and Piacenza (8.65 pg
      WHO-TEQ in Giugliano vs. 11.0 and 9.94 pg WHO-TEQ in Milan and Piacenza
      respectively). Thus no direct correlations were found between PCDD/F and PCB
      levels in breast milk and the suspected increased exposure through open-air waste
      combustion in Giugliano. Diet did not seem to affect PCDD/F and PCB levels,
      whereas a significant correlation was observed between the mother's age and an
      increased concentration of PCDDs/Fs and PCBs in milk. Comparison of these
      findings with those of previous surveys in Italy in 2000-2001 showed a marked
      reduction of PCDD/F (about 60%) and DL-PCB (about 20%) levels in breast milk
      occurring over the last 10 years. This might well be a result of well functioning
      legislation, for example European Directives on of the reduction of the emission
      limits of PCDDs/Fs and PCBs from waste incineration set by EU Directive
      2000/76/EC implemented in 2000, or Commission Regulations such as (EC) No.
      466/2001 and 1881/2006 setting maximum levels for certain contaminants in
      foodstuffs.

PMID- 21074247
TI  - Platelets as central mediators of systemic inflammatory responses.
AB  - Systemic inflammatory responses are associated with high morbidity and mortality
      and represent a diverse and clinically challenging group of diseases. Platelets
      are increasingly linked to inflammation, in addition to their well-known roles in
      hemostasis and thrombosis. There is agreement that traditional functions of
      platelets, including adherence, aggregation, and secretion of preformed
      mediators, contribute to systemic inflammatory responses. However, emerging
      evidence indicates that platelets function in non-traditional ways. In this
      review, we focus on new functions of platelets that may be involved in the host
      response to infection.

PMID- 21074248
TI  - The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and
      proliferation in the PTEN pathway.
AB  - PI3K and PTEN lipid phosphatase control the level of cellular
      phosphatidylinositol (3,4,5)-trisphosphate, an activator of AKT kinases that
      promotes cell growth and survival. Mutations activating AKT are commonly observed
      in human cancers. We report here that ENTPD5, an endoplasmic reticulum (ER)
      enzyme, is upregulated in cell lines and primary human tumor samples with active
      AKT. ENTPD5 hydrolyzes UDP to UMP to promote protein N-glycosylation and folding
      in ER. Knockdown of ENTPD5 in PTEN null cells causes ER stress and loss of growth
      factor receptors. ENTPD5, together with cytidine monophosphate kinase-1 and
      adenylate kinase-1, constitute an ATP hydrolysis cycle that converts ATP to AMP,
      resulting in a compensatory increase in aerobic glycolysis known as the Warburg
      effect. The growth of PTEN null cells is inhibited both in vitro and in mouse
      xenograft tumor models. ENTPD5 is therefore an integral part of the PI3K/PTEN
      regulatory loop and a potential target for anticancer therapy.

PMID- 21074249
TI  - Expression of claudin-1 and -11 in immature and mature pheasant (Phasianus
      colchicus) testes.
AB  - The expression of claudin-1 and -11, tight junctions (TJs) proteins was examined
      in immature and adult pheasant (Phasianus colchicus) testes. Claudin-1 and -11
      cDNA were highly similar to those of human, mice, and chicken. Claudin-1 mRNA and
      protein (21 kDa) levels in immature testes were higher than those of adult
      testis. In immature testes until 6 weeks of age, Claudin-1 was found at contacts
      between adjacent Sertoli cells and between Sertoli cells and germ cells. In adult
      testis, Claudin-1 was found in early spermatocytes migrating the blood testis
      barrier (BTB). Blood vessels were positive for claudin-1. Claudin-11 mRNA and
      protein (21 kDa) increased during adulthood development of testis. In immature
      testis, Claudin-11 was found in apicolateral contacts between adjacent Sertoli
      cells, indicating its involvement in cell adhesion in immature testis. In adult
      testis, strong wavy Claudin-11 immunoreactivity was parallel to basal lamina at
      the basal part of seminiferous epithelium, indicating that Claudin-11 at the
      inter-Sertoli TJs may act as a structural element of the BTB. Weak Claudin-1 and 
      11 immunoreactivity at contacts between Sertoli cells to elongating/elongated
      spermatids, meiotic germ cells, and basal lamina suggests that they also
      participate in the cell-cell and cell-extracellular matrix adhesion in pheasant
      testis. Testosterone increased claudin-11 mRNA in testis organ culture and
      Sertoli cell primary culture, suggesting positive regulation of claudin-11 gene
      by androgen in Sertoli cells of pheasant testis. This is the first report on the
      claudins expression at BTB in avian testis.

PMID- 21074250
TI  - Effect of reducing agents on bond strength to NaOCl-treated dentin.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of three
      antioxidant/reducing agents with different application times on microtensile bond
      strengths to sodium hypochlorite-treated dentin. METHODS: The occlusal surfaces
      of 24 extracted human third molars were horizontally cut to expose sound dentin.
      The teeth were divided into eight groups. The dentin surfaces of the teeth were
      treated as follows: group 1, no treatment; group 2, treated with 6% sodium
      hypochlorite (NaOCl) for 30s; groups 3-8, applications of 10% sodium ascorbate
      solution, 100 MUM rosmarinic acid solution or Accel for 5 or 10s after the same
      treatment as in group 2. All treated dentin surfaces were bonded with a 2-step
      self-etching adhesive system (Clearfil Protect Bond) and restored with a resin
      composite (Clearfil AP-X). After storage in water for 24h, the bonded specimens
      were subjected to the microtensile bond test at a crosshead speed of 1.0 mm/min.
      Data were analyzed by a one-way ANOVA and Tukey test (p<0.05). RESULTS: The NaOCl
      treated group had significantly lower bond strength than the control group
      (p<0.05). The application of sodium ascorbate solution for 5 or 10s did not
      significantly increase the compromised bonding to NaOCl-treated dentin (p>0.05).
      On the other hand, Accel and rosmarinic acid solution had significant reversal
      effects with the same application times (p<0.05). SIGNIFICANCE: The reversal
      effect on compromised bonding to NaOCl-treated dentin depended upon the type of
      antioxidant within the short application time. Applying Accel or rosmarinic acid
      for 5 or 10s improved bond strengths to NaOCl-treated dentin.

PMID- 21074251
TI  - Cytotoxicity of current adhesive systems: in vitro testing on cell cultures of
      primary murine macrophages.
AB  - OBJECTIVES: The aim of this study was to evaluate, in vitro, the potential
      cytotoxicity of dentinal adhesives on alveolar macrophages of Wistar rats, after
      diffusion through dentin. METHODS: The cytotoxicity of adhesives [single bond
      plus (SB), clearfil SE bond (CF) and Xeno V (XE)] applied to the occlusal surface
      of human dentin disks adapted to a dentin barrier test device were analyzed. The
      sets placed on a monolayer of cells were incubated for 24, 48 and 72h. Culture
      medium and Escherichia coli lipopolysaccharides (LPS) were used as negative and
      positive controls, respectively. Cellular cytotoxicity was evaluated by observing
      the cell survival rate (MTT assay) and nitric oxide production (NO). The data
      were analyzed by one-way factorial ANOVA and Tukey's and Tamhane's paired
      comparisons T2 (alpha=0.05). RESULTS: All the adhesive systems reduced the
      percentage of live cells by over 50%, compared with the control group. Within the
      same period of time, there was a statistically significant difference between the
      adhesives and LPS compared with the negative control group. SB presented a
      statistically significant difference between 24h and 72h, and XE between 48h and
      72h. The quantity of NO produced in 24h did not differ statistically between the
      NC and adhesive groups. After 48h there was a significant difference between
      SB/CF and XE/NC. At 72h only CF showed a significant difference from each of the
      other groups. LPS differed statistically from all the other groups at all the
      evaluation times. SIGNIFICANCE: Components of the adhesives tested may permeate
      the dentin in sufficient concentrations to cause death and damage to cell
      metabolism in the alveolar macrophages of rats, which indicates potential
      cytotoxicity to pulpal cells.

PMID- 21074252
TI  - Mobilising the world for chronic NCDs.

PMID- 21074253
TI  - Prevention and management of chronic disease: a litmus test for health-systems
      strengthening in low-income and middle-income countries.
AB  - National health systems need strengthening if they are to meet the growing
      challenge of chronic diseases in low-income and middle-income countries. By
      application of an accepted health-systems framework to the evidence, we report
      that the factors that limit countries' capacity to implement proven strategies
      for chronic diseases relate to the way in which health systems are designed and
      function. Substantial constraints are apparent across each of the six key health
      systems components of health financing, governance, health workforce, health
      information, medical products and technologies, and health-service delivery.
      These constraints have become more evident as development partners have
      accelerated efforts to respond to HIV, tuberculosis, malaria, and vaccine
      preventable diseases. A new global agenda for health-systems strengthening is
      arising from the urgent need to scale up and sustain these priority
      interventions. Most chronic diseases are neglected in this dialogue about health
      systems, despite the fact that non-communicable diseases (most of which are
      chronic) will account for 69% of all global deaths by 2030 with 80% of these
      deaths in low-income and middle-income countries. At the same time, advocates for
      action against chronic diseases are not paying enough attention to health systems
      as part of an effective response. Efforts to scale up interventions for
      management of common chronic diseases in these countries tend to focus on one
      disease and its causes, and are often fragmented and vertical. Evidence is
      emerging that chronic disease interventions could contribute to strengthening the
      capacity of health systems to deliver a comprehensive range of services-provided
      that such investments are planned to include these broad objectives. Because
      effective chronic disease programmes are highly dependent on well-functioning
      national health systems, chronic diseases should be a litmus test for health
      systems strengthening.

PMID- 21074254
TI  - Scrambling for Africa? Universities and global health.

PMID- 21074255
TI  - Tackling of unhealthy diets, physical inactivity, and obesity: health effects and
      cost-effectiveness.
AB  - The obesity epidemic is spreading to low-income and middle-income countries as a
      result of new dietary habits and sedentary ways of life, fuelling chronic
      diseases and premature mortality. In this report we present an assessment of
      public health strategies designed to tackle behavioural risk factors for chronic
      diseases that are closely linked with obesity, including aspects of diet and
      physical inactivity, in Brazil, China, India, Mexico, Russia, and South Africa.
      England was included for comparative purposes. Several population-based
      prevention policies can be expected to generate substantial health gains while
      entirely or largely paying for themselves through future reductions of health
      care expenditures. These strategies include health information and communication
      strategies that improve population awareness about the benefits of healthy eating
      and physical activity; fiscal measures that increase the price of unhealthy food
      content or reduce the cost of healthy foods rich in fibre; and regulatory
      measures that improve nutritional information or restrict the marketing of
      unhealthy foods to children. A package of measures for the prevention of chronic
      diseases would deliver substantial health gains, with a very favourable cost
      effectiveness profile.

PMID- 21074256
TI  - Medical schools in sub-Saharan Africa.
AB  - Small numbers of graduates from few medical schools, and emigration of graduates
      to other countries, contribute to low physician presence in sub-Saharan Africa.
      The Sub-Saharan African Medical School Study examined the challenges,
      innovations, and emerging trends in medical education in the region. We
      identified 168 medical schools; of the 146 surveyed, 105 (72%) responded.
      Findings from the study showed that countries are prioritising medical education
      scale-up as part of health-system strengthening, and we identified many
      innovations in premedical preparation, team-based education, and creative use of
      scarce research support. The study also drew attention to ubiquitous faculty
      shortages in basic and clinical sciences, weak physical infrastructure, and
      little use of external accreditation. Patterns recorded include the growth of
      private medical schools, community-based education, and international
      partnerships, and the benefit of research for faculty development. Ten
      recommendations provide guidance for efforts to strengthen medical education in
      sub-Saharan Africa.

PMID- 21074257
TI  - Rethinking health-care systems: a focus on chronicity.

PMID- 21074258
TI  - Monitoring and surveillance of chronic non-communicable diseases: progress and
      capacity in high-burden countries.
AB  - The burden of chronic, non-communicable diseases in low-income and middle-income
      countries is increasing. We outline a framework for monitoring of such diseases
      and review the mortality burden and the capacity of countries to respond to them.
      We show data from WHO data sources and published work for prevalence of tobacco
      use, overweight, and cause-specific mortality in 23 low-income and middle-income
      countries with a high burden of non-communicable disease. Data for national
      capacity for chronic disease prevention and control were generated from a global
      assessment that was done in WHO member states in 2009-10. Although reliable data
      for cause-specific mortality are scarce, non-communicable diseases were estimated
      to be responsible for 23.4 million (or 64% of the total) deaths in the 23
      countries that we analysed, with 47% occurring in people who were younger than 70
      years. Tobacco use and overweight are common in most of the countries and
      populations we examined, but coverage of cost-effective interventions to reduce
      these risk factors is low. Capacity for prevention and control of non
      communicable diseases, including monitoring and surveillance operations
      nationally, is inadequate. A surveillance framework, including a minimum set of
      indicators covering exposures and outcomes, is essential for policy development
      and assessment and for monitoring of trends in disease. Technical, human, and
      fiscal resource constraints are major impediments to the establishment of
      effective prevention and control programmes. Despite increasing awareness and
      commitment to address chronic disease, concrete actions by global partners to
      plan and implement cost-effective interventions are inadequate.

PMID- 21074259
TI  - Health, agricultural, and economic effects of adoption of healthy diet
      recommendations.
AB  - Transition to diets that are high in saturated fat and sugar has caused a global
      public health concern, as the pattern of food consumption is a major modifiable
      risk factor for chronic non-communicable diseases. Although agri-food systems are
      intimately associated with this transition, agriculture and health sectors are
      largely disconnected in their priorities, policy, and analysis, with neither side
      considering the complex inter-relation between agri-trade, patterns of food
      consumption, health, and development. We show the importance of connection of
      these perspectives through estimation of the eff ect of adopting a healthy diet
      on population health, agricultural production, trade, the economy, and
      livelihoods,with a computable general equilibrium approach. On the basis of case
      studies from the UK and Brazil, we suggest that benefits of a healthy diet policy
      will vary substantially between different populations, not only because of
      population dietary intake but also because of agricultural production, trade, and
      other economic factors.

PMID- 21074261
TI  - Chronic diseases: global action must match global evidence.

PMID- 21074260
TI  - Raising the priority of preventing chronic diseases: a political process.
AB  - Chronic diseases, especially cardiovascular diseases, diabetes, cancer, and
      chronic obstructive respiratory diseases,are neglected globally despite growing
      awareness of the serious burden that they cause. Global and national policies
      have failed to stop, and in many cases have contributed to, the chronic disease
      pandemic. Low-cost and highly effective solutions for the prevention of chronic
      diseases are readily available; the failure to respond is now a political, rather
      than a technical issue. We seek to understand this failure and to position
      chronic disease centrally on the global health and development agendas. To
      identify strategies for generation of increased political priority for chronic
      diseases and to further the involvement of development agencies, we use an
      adapted political process model. This model has previously been used to assess
      the success and failure of social movements. On the basis of this analysis,we
      recommend three strategies: reframe the debate to emphasise the societal
      determinants of disease and the interrelation between chronic disease, poverty,
      and development; mobilise resources through a cooperative and inclusive approach
      to development and by equitably distributing resources on the basis of avoidable
      mortality; and build one merging strategic and political opportunities, such as
      the World Health Assembly 2008-13 Action Plan and the high level meeting of the
      UN General Assembly in 2011 on chronic disease. Until the full set of threats
      which include chronic disease-that trap poor households in cycles of debt and
      illness are addressed, progress towards equitable human development will remain
      inadequate.

PMID- 21074262
TI  - Extracellular matrix production by adipose-derived stem cells: implications for
      heart valve tissue engineering.
AB  - A key challenge in tissue engineering a heart valve is to reproduce the major
      tissue structures responsible for native valve function. Here we evaluated human
      adipose-derived stem cells (ADSCs) as a source of cells for heart valve tissue
      engineering investigating their ability to synthesize and process collagen and
      elastin. ADSCs were compared with human bone marrow mesenchymal stem cells
      (BmMSCs) and human aortic valve interstitial cells (hVICs). ADSCs and BmMSCs were
      stretched at 14% for 3 days and collagen synthesis determined by [(3)H]-proline
      incorporation. Collagen and elastin crosslinking was assessed by measuring
      pyridinoline and desmosine respectively, using liquid chromatography/mass
      spectrometry. Three-dimensional culture was obtained by seeding cells onto bovine
      collagen type I scaffolds for 2-20 days. Expression of matrix proteins and
      processing enzymes was assessed by Real Time-PCR, immunofluorescence and
      transmission electron microscopy. Stretch increased the incorporation of [(3)H]
      proline in ADSCs and BmMSCs, however only ADSCs and hVICs upregulated COL3A1
      gene. ADSCs produced collagen and elastin crosslinks. ADSCs uniformly populated
      collagen scaffolds after 2 days, and fibrillar-like collagen was detected after
      20 days. ADSCs sense mechanical stimulation and produce and process collagen and
      elastin. These novel findings have important implications for the use of these
      cells in tissue engineering.

PMID- 21074263
TI  - Human ferritin cages for imaging vascular macrophages.
AB  - Atherosclerosis is a leading cause of death worldwide. Macrophages are key
      components of vascular inflammation, which contributes to the development and
      complications of atherosclerosis. Ferritin, an iron storage and transport
      protein, has been found to accumulate in macrophages in human atherosclerotic
      plaques. We hypothesized that ferritin could serve as an intrinsic nano-platform
      to target delivery of imaging agents to vascular macrophages to detect high-risk
      atherosclerotic plaques. Here we show that engineered human ferritin protein
      cages, either conjugated to the fluorescent Cy5.5 molecule or encapsulating a
      magnetite nanoparticle, are taken up in vivo by macrophages in murine
      atherosclerotic carotid arteries and can be imaged by fluorescence and magnetic
      resonance imaging. These results indicate that human ferritin can serve as a
      nanoparticle platform to image vascular inflammation in vivo.

PMID- 21074264
TI  - The influence of scaffold architecture on chondrocyte distribution and behavior
      in matrix-associated chondrocyte transplantation grafts.
AB  - Scaffold architecture and composition are important parameters in cartilage
      tissue engineering. In this in vitro study, we compared the morphology of four
      different cell-graft systems applied in clinical cartilage regeneration and
      analyzed the cell distribution (DAPI nuclei staining) and cell-scaffold
      interaction (SEM, TEM). Our investigations revealed major differences in cell
      distribution related to scaffold density, pore size and architecture. Material
      composition influenced the quantity of autogenous matrix used for cellular
      adhesion. Cell bonding was further influenced by the geometry of the scaffold
      subunits. On scaffolds with widely spaced fibers and a thickness less than the
      cell diameter, chondrocytes surrounded the scaffold fibers with cell extensions.
      On those fibers, chondrocytes were spherical, suggesting a differentiated
      phenotype. Fiber sizes smaller than chondrocyte size, and widely spaced, are
      therefore beneficial in terms of improved adhesion by cell shape adaptation. They
      also support the differentiated stage of chondrocytes by preventing the
      fibroblast-like and polygonal cell shape, at least briefly.

PMID- 21074265
TI  - Protein composition of microparticles shed from human placenta during placental
      perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia.
AB  - Shedding of syncytiotrophoblast microparticles (MPs) from placenta to maternal
      blood occurs in normal pregnancy and is enhanced during preeclampsia (PE). The
      syncytiotrophoblast synthesizes plasminogen activator inhibitors (PAIs) which
      regulate fibrinolysis, as well as soluble forms of the fms-like tyrosine kinase
      (sFlt-1) and endoglin, which exert anti-angiogenic actions. An increase in the
      ratio of PAI-1/PAI-2 and elevated levels of sFlt-1 and sEng in maternal serum are
      linked to placental damage and maternal endothelial cell dysfunction in PE. The
      goal of the current study was to determine whether MPs released to maternal
      perfusate during dual perfusion contain these factors associated with placental
      pathophysiology in PE. Initially, high levels of alkaline phosphatase activity
      and Annexin V binding were found in MPs isolated by sequential centrifugation of
      maternal perfusates at 10,000 and 150,000*g(10 K and 150 K MPs), indicating their
      plasma membrane origin. ELISA revealed the presence of these factors at the
      following relative levels: Eng>PAI-2?PAI-1>sFlt-1. Based on comparisons of their
      concentration in perfusates, MPs, and MP-free 150 K supernatants, we determined
      that MPs constitute a significant portion of Eng released by placenta. Flow
      cytometric analysis of 10 K MPs supported the levels of expression found by ELISA
      and indicated that Eng and PAI-2 were almost exclusively localized to the surface
      of MPs, a site with biological potential. These results indicate that MPs shed
      from the syncytial surface express factors which may alter the fibrinolytic and
      angiogenic balance at the maternal-fetal interface and play a role in the
      pathophysiology of PE.

PMID- 21074266
TI  - CDDO-Im, an antitumor molecule that also improves platetet production.

PMID- 21074268
TI  - Conventional cytogenetics in chronic lymphocytic leukemia (CLL).

PMID- 21074267
TI  - It takes two-to-leukemia: about addictions and requirements.

PMID- 21074269
TI  - Abnormal methylation of GRAF promoter Chinese patients with acute myeloid
      leukemia.
AB  - The epigenetic disturbances are recognized as an alternative mechanism
      contributing to the pathogenesis of acute myeloid leukemia (AML). GTPase
      regulator associated with focal adhesion kinase (GRAF), a putative tumor
      suppressor gene, was revealed with mutations and promoter methylation in AML and
      myelodysplastic syndrome. In this study, we investigated the methylation status
      of GRAF promoter in Chinese AML patients. Aberrant methylation of GRAF promoter
      was detected in 66.7% (88/132) of the cases analyzed. The methylation of GRAF
      gene could be detected in all FAB subtypes and in all cytogenetic risk groups.
      There were no significant differences in clinical features, FAB subtypes and
      cytogenetic risk groups between patients with and without GRAF methylation. GRAF
      transcript was significantly lower in AML group compared to controls (3.30 vs
      56.06, P<0.001). Both patients with methylated GRAF gene and those without
      methylated GRAF gene had significantly lower GRAF transcript than controls
      (P<0.001). Furthermore, GRAF transcript was significantly lower in patients with
      methylated GRAF than those without methylated GRAF (1.64 vs 6.42, P=0.005). These
      findings suggest that the hypermethylation of GRAF promoter might be one of early
      events in the development of AML.

PMID- 21074270
TI  - Salvaging AML with CLAG: novel option, or more of the same?

PMID- 21074271
TI  - Systematic mutation and thermodynamic analysis of central tyrosine pairs in
      polyspecific NKG2D receptor interactions.
AB  - The homodimeric, activating natural killer cell receptor NKG2D interacts with
      multiple monomeric ligands polyspecifically, yet without central conformational
      flexibility. Crystal structures of multiple NKG2D-ligand interactions have
      identified the NKG2D tyrosine pair Tyr 152 and Tyr 199 as forming multiple
      specific but diverse interactions with MICA and related proteins. Here we
      systematically altered each tyrosine to tryptophan, phenylalanine, isoleucine,
      leucine, valine, serine, and alanine to measure the effect of mutation on
      affinity and thermodynamics for binding a range of similar ligands: MICA, the
      higher-affinity ligand MICB, and MICdesign, a high-affinity version of MICA that
      shares all NKG2D contact residues with MICA. Affinity and residue size were
      related: tryptophan could often substitute for tyrosine without loss of affinity;
      loss of the tyrosine hydroxyl through mutation to phenylalanine was tolerated
      more at position 152 than 199; and the smallest residues coincide with lowest
      affinities in general. NKG2D mutant van't Hoff binding thermodynamics generally
      show that substitution of other residues for tyrosine causes a moderate positive
      or flat van't Hoff slope consistent with moderate loss of binding enthalpy. One
      set of NKG2D mutations caused MICA to adopt a positive van't Hoff slope
      corresponding to absorption of heat, and another set caused MICB to adopt a
      negative slope of greater heat release than wild-type. MICdesign shared one
      example of the first set with MICA and one of the second set with MICB. When the
      NKG2D mutation affinities were arranged according to change in nonpolar surface
      area and compared to results from specific antibody-antigen and protein-peptide
      interactions, it was found that hydrophobic surface loss in NKG2D reduced binding
      affinity less than reported in the other contexts. The hydrophobic effect at the
      center of the NKG2D binding appears more similar to that at the periphery of an
      antibody-antigen binding site than at its center. Therefore the polyspecific
      NKG2D binding site is more tolerant of structural alteration in general than
      either an antibody-antigen or protein-peptide binding site, and this tolerance
      may adapt NKG2D to a broad range of protein surfaces with micromolar affinity.

PMID- 21074272
TI  - Incidence of major depressive episode correlates with elevation of substate
      region of residence.
AB  - BACKGROUND: Major depressive disorder (MDD) is a common disorder that is often
      associated with suicide. We have recently suggested that elevation may play a
      role in regional variations in rates of suicide. We hypothesize that there is
      also a significant correlation between incidence of MDD and elevation of
      residence. METHODS: The substate estimates from the 2004 to 2006 National Surveys
      on Drug Use and Health (NSDUH) report from SAMHSA was used to extract substate
      level data related to percentages of people 18 years or older who experienced
      serious psychological distress or a major depressive episode in the past year.
      Mean elevation of each substate region was calculated by averaging the weighted
      elevations of its relevant counties. Average elevation for United States counties
      was calculated using the Shuttle Radar Topography Mission (SRTM) elevation
      dataset. Pearson correlation coefficients were computed to investigate the
      association between average substate elevation and rate of serious psychological
      distress or major depressive episode. RESULTS: There was a significant
      correlation between percentage of people experiencing serious psychological
      distress in the past year in a substate region and that substate region's mean
      elevation (r=0.18; p=0.0005), as well as between the percentage of people having
      at least one major depressive episode in the past year in a substate region and
      that substate region's mean elevation (r=0.27; p0.0001). CONCLUSIONS: Elevation
      appears to be a significant risk factor for MDD. Further studies are indicated to
      determine whether the increased incidence of depression with increased elevation
      may be due to the hypoxic effects on subjects with MDD.

PMID- 21074273
TI  - Patterns of Axis I comorbidity in relation to age in patients with Bipolar
      Disorder: a cross-sectional analysis.
AB  - BACKGROUND: Several data indicate that the clinical course and treatment response
      of Bipolar Disorder (BD) is influenced by comorbidity. However, whether
      differences in comorbidity patterns exist in relation to classes of age remains
      debated. The present study was aimed to evaluate differences in terms of cross
      sectional Axis I comorbidity among young (<=30 years), adult (>30 and <=45 years)
      and older adult patients with BD (>45 years). METHODS: Study sample included 508
      patients with BD, subdivided into 3 groups of age: <=30 years (n=52), >30 and
      <=45 years (n=186) and >45 years (n=270). Demographic and clinical variables,
      with specific emphasis on Axis I comorbidity, were compared across the different
      groups using chi-square tests. Furthermore, a binary logistic regression was
      performed. RESULTS: Two-hundred eleven patients (41.5%) showed at least another
      concomitant Axis I disorder. The 3 groups were homogenous in terms of type of
      diagnosis (type 1 or 2 BD) and gender. However, they were different in terms of
      cross-sectional Axis I comorbidity (p=0.001) with a higher frequency of substance
      abuse (p=0.04) and Anorexia (p=0.014) in young patients, and of Obsessive
      Compulsive Disorder in adult patients (p=0.001). In addition, young patients
      showed more frequently the presence of a second comorbid Axis I condition
      compared to the other sub-groups (p=0.05). With regard to the type of abuse,
      young subjects were more frequently cannabis (p<0.001) and cocaine abusers
      (p<0.001) compared to the other subgroups. LIMITATIONS: Lifetime Axis I and Axis
      II and cross-sectional Axis II comorbidity patterns were not analyzed.
      CONCLUSIONS: Preliminary results from the present exploratory study seem to
      suggest different profiles of cross-sectional Axis I comorbidity and abuse in
      bipolar patients in relation to age. This aspect should be taken into account for
      the choice of pharmacological treatments and global management in clinical
      practice.

PMID- 21074274
TI  - Cognitive functions among euthymic bipolar I patients after a single manic
      episode versus recurrent episodes.
AB  - BACKGROUND: There is a growing consensus that persistent cognitive deficits are
      common in patients with bipolar disorders even when they are euthymic. AIM: The
      aim was to assess objectively the presence of cognitive deficits in bipolar
      patients in remission, and to correlate these deficits with the recurrence of the
      disease. METHODS: Cognitive functions (executive function, memory, intelligence,
      attention and concentration) of a group of euthymic bipolar patients after a
      single manic episode were compared to cognitive functions of patients who
      experienced recurrent episodes, both groups were assessed during remission. The
      results were compared with a control group, using SPSS. RESULTS: Euthymic bipolar
      patients assessed after a single manic episode showed impairment in attention,
      executive functions and total memory score in comparison to healthy control
      subjects. While they performed better than Euthymic bipolar patients assessed
      after recurrent bipolar episodes as regards attention and executive function.
      CONCLUSION: Bipolar disorder is associated with attention, memory and executive
      dysfunction. Attention and executive dysfunction is deteriorated by the
      recurrence of bipolar episodes.

PMID- 21074276
TI  - Regulation of IgA responses in cattle, humans and mice.
AB  - Secretory IgA (SIgA) constitutes the largest component of the humoral immune
      system of the body with gram quantities of this isotype produced by mammals on a
      daily basis. Secretory IgA (SIgA) antibodies function by both blocking
      pathogen/commensal entry at mucosal surfaces and virus neutralization. Several
      pathways of induction of IgA responses have been described which depend on T
      cells (T cell dependent or TD) pathways or are independent of T cells (T
      independent or TI) and are mediated by dendritic cells (DCs) and/or epithelial
      cells. Many elements of IgA regulation readily cross species barriers (adjuvants,
      soluble and cognate factors) and are highly conserved whereas other pathways may
      be more specific to any given species and must be evaluated. Regulation of IgA
      production in cattle is not completely understood and thus we have focused in
      part on highly conserved factors such as transforming growth factor beta, Type I
      and Type 2 interferons, neuropeptides which interdigitate mucosal tissues
      (vasoactive intestinal peptide or VIP), and a small peptide (IgA inducing peptide
      or IGIP) which can serve as targets for modulation and increasing SIgA virus
      specific antibodies. We have evaluated the potential utility of modulating these
      factors in vitro in regulation of qualitative aspects of antibodies of the IgM,
      IgG and IgA isotypes at mucosal surfaces and in secretions of the upper and lower
      respiratory tract to a virus of economic and public health importance, foot and
      mouth disease virus (FMDV). IgA responses in cattle are essential for host
      defense in response to various infectious agents. In cattle, IgA is not released
      into the colostrum, as is the case for other mammals but only IgG1 is selectively
      transported. In previous studies in cattle, IgA has been shown to be regulated by
      several cytokines including IFN-gamma, Type I interferons such as IFN-alpha and
      IFN-tau, transforming growth factor beta, IgA inducing peptide and other
      potential factors such as APRIL and BlyS which have not yet been fully evaluated
      in cattle. Many of these factors, namely TGF-beta and Type I interferons block
      cell cycle progression which is an essential component of Ig class switching and
      thus these factors require additional regulatory factors such as IL-2 to drive
      cells through cell cycle resulting in class switch recombination. Among these
      factors, IgA inducing peptide was originally identified from a bovine gut
      associated lymphoid tissue expression library and is highly conserved in pigs and
      humans at >90% at the amino acid level. The factor is regulated differently in
      various species but is consistently produced by dendritic cells.

PMID- 21074277
TI  - Utility, limitations, and promise of proteomics in animal science.
AB  - Proteomics experiments have the ability to simultaneously identify and quantify
      thousands of proteins in one experiment. The use of this technology in
      veterinary/animal science is still in its infancy, yet it holds significant
      promise as a method for advancing veterinary/animal science research. Examples of
      current experimental designs and capabilities of proteomic technology and basic
      principles of mass spectrometry are discussed. In addition, challenges and
      limitations of proteomics are presented, stressing those that are unique to
      veterinary/animal sciences.

PMID- 21074278
TI  - Immunohistochemical detection of extrinsic and intrinsic mediators of apoptosis
      in porcine paraffin-embedded tissues.
AB  - Apoptosis is a strictly regulated mechanism of cell death that involves a complex
      network of biochemical pathways. Whether a cell undergoes apoptosis or not
      depends on a delicate balance of anti- and pro-apoptotic stimuli. This phenomenon
      can be induced by two different pathways: intrinsic and extrinsic pathways. The
      main aim of this study was to determine the ideal fixative and antigen retrieval
      method in porcine paraffin embedded tissues for the immunohistochemical detection
      of apoptosis mediators, from both extrinsic and intrinsic pathways. Tonsil,
      retropharyngeal lymph node and lung tissue samples were fixed in 10% neutral
      buffered formalin, Bouin solution and zinc salts fixative (ZSF) and different
      unmasking methods were carried out. Both 10% neutral buffered formalin and ZSF
      resulted as the fixatives of election to study apoptosis phenomena. Tween 20
      (0.01% in PBS), citrate buffer (microwave, pH 6.0) and/or protease type XIV were
      the antigen retrieval methods which displayed better labelling. Our results allow
      to deep in the knowledge of apoptosis and its role in the pathogenesis of porcine
      diseases.

PMID- 21074279
TI  - Acquired cholesteatoma in children following congenital cholesteatoma surgery.
AB  - OBJECTIVES: To determine the incidence of severe atelectatic otitis media and
      acquired cholesteatoma (AC) in children treated for congenital cholesteatoma
      (CC). METHODS: Retrospective chart review of 15 children who underwent primary
      surgery for CC over a 15 year period by a single surgeon. RESULTS: The mean
      postoperative follow up was 3.1 years. Significant tympanic retraction occurred
      in 6 children, included a retraction pocket that required T-tube insertion (3),
      and AC requiring tympanomastoid surgery (3). There was no complication related to
      retraction pocket in 9 children however 2 developed residual disease. In
      comparing the two groups, those with and without subsequent significant tympanic
      retraction, both groups had similar gender, age, extent of CC (median Potsic
      grade of 2), bone erosion, and surgical technique. Differences were noted in air
      bone gap at presentation (PTA 32.4 and 17.25), otitis media with effusion in the
      contralateral ear (3/6 and 1/9), smaller mastoid volume ratio compared with the
      contralateral ear (0.74 and 1.21), and longer average timing for second surgery
      (14.8 months and 8 months). CONCLUSIONS: Acquired middle ear disease, including
      cholesteatoma, can follow surgical removal of CC, and long term follow up of all
      patients is required. Factors at initial evaluation indicative of risk of AC
      include a significant air-bone gap, otitis media with effusion in the
      contralateral ear and a smaller mastoid cavity ratio. The use of composite grafts
      at the time of CC surgery should be considered. Additionally, our findings
      suggest that the mastoid volume plays a causative role in the development of AC.

PMID- 21074280
TI  - Thermal welding vs. cold knife tonsillectomy: a comparison of voice and speech.
AB  - OBJECTIVE: To compare acoustic, aerodynamic and perceptual voice and speech
      parameters in thermal welding system tonsillectomy and cold knife tonsillectomy
      patients in order to determine the impact of operation technique on voice and
      speech. METHODS: Thirty tonsillectomy patients (22 children, 8 adults)
      participated in this study. The preferred technique was cold knife tonsillectomy
      in 15 patients and thermal welding system tonsillectomy in the remaining 15
      patients. One week before and 1 month after surgery the following parameters were
      estimated: average of fundamental frequency, Jitter, Shimmer, harmonic to noise
      ratio, formant frequency analyses of sustained vowels. Perceptual speech analysis
      and aerodynamic measurements (maximum phonation time and s/z ratio) were also
      conducted. RESULTS: There was no significant difference in any of the parameters
      between cold knife tonsillectomy and thermal welding system tonsillectomy groups
      (p>0.05). When the groups were contrasted among themselves with regards to
      preoperative and postoperative rates, fundamental frequency was found to be
      significantly decreased after tonsillectomy in both of the groups (p<0.001).
      First formant for the vowel /a/ in the cold knife tonsillectomy group and for the
      vowel /i/ in the thermal welding system tonsillectomy group, second formant for
      the vowel /u/ in the thermal welding system tonsillectomy group and third formant
      for the vowel /u/ in the cold knife tonsillectomy group were found to be
      significantly decreased (p<0.05). CONCLUSIONS: The surgical technique, whether it
      is cold knife or thermal welding system, does not appear to affect voice and
      speech in tonsillectomy patients.

PMID- 21074281
TI  - Noise levels in a neonatal transport incubator in medically configured aircraft.
AB  - OBJECTIVE: The purpose of this study was to evaluate exposure of neonates to
      noise during air medical transport as few commercially available hearing
      protective devices exist for premature newborns during air medical transport.
      METHODS: Sound pressure levels in an infant incubator during actual flight
      conditions in four common medically configured aircraft were measured. Three
      noise dosimeters measured time-weighted average noise exposure during flight in
      each aircraft. One dosimeter was placed in the infant incubator, and the
      remaining dosimeters recorded noise levels in various parts of the aircraft
      cabin. RESULTS: The incubator provided a 6-dBA decrease in noise exposure from
      that in the crew cabin. The average noise level in the incubator in all aircraft
      was close to 80 dB, much higher than the proposed limits of 45 dB for neonatal
      intensive care unit noise exposure or 60 dB during transport. CONCLUSIONS:
      Exposure of neonates to elevated noise levels during transport may be harmful,
      and steps should be taken to protect the hearing of this patient population.

PMID- 21074282
TI  - Health-related quality of life in children and adolescents who use cochlear
      implants.
AB  - OBJECTIVE: Examination of health-related quality of life (HRQoL) in children and
      adolescents who wear a cochlear implant (CI) primarily has depended on parent
      proxy report of the child's HRQoL rather than child self-report and generic
      domains rather than CI-specific issues. This study simultaneously assessed self
      report ratings on a generic HRQoL instrument and a preliminary CI module in
      pediatric CI users. The impact of demographic factors (chronologic age, age at
      CI, and CI experience) on HRQoL also was explored. METHODS: This cross-sectional
      study included 138 children grouped by chronologic age: 4-7, 8-11 and 12-16
      years. The KINDL(R) questionnaire for measuring HRQoL in children and adolescents
      (generic) and a preliminary CI module (specific) were completed as a researcher
      administered interview (4-7 years) or self-administered questionnaire (8-16
      years) at CI summer camp or home. Scores were transformed to a 100-point scale
      with 100 representing the most positive response. The impact of chronologic age
      group on HRQoL ratings was evaluated using Analysis of Variance. Spearman rank
      order correlations and point-biserial correlations tested associations between
      demographic factors and HRQoL scores. Principal factor analysis was used to
      discover the factor structure and internal consistency of the preliminary CI
      module. RESULTS: The youngest group (M=82.8) rated generic HRQoL significantly
      more positively than older children (8-11 years: M=75.3; 12-16 years: M=70.4).
      Similar significant results emerged on the overall CI module (4-7 years: M=79.8;
      8-11 years: M=77.8; 12-16 years: M=71.3). The youngest group rated CI-specific
      items on friends and self-image more positively than older groups, but reported
      greater difficulties hearing teachers at school. The oldest group provided more
      consistent responses than younger groups on the CI module (Cronbach alpha=0.72).
      Generic and CI module scores correlated positively (r=0.19, p=.03) but this
      association reflects the strong correlation in the oldest group (r=0.49,
      p=0.0033) and camouflages non-significant results in younger groups. CONCLUSION:
      Chronologic age impacts self-report of HRQoL for pediatric CI users such that
      younger children rate HRQoL more positively than older children and adolescents
      on a generic instrument and preliminary CI module. Older children provide more
      consistent responses on the CI module. Results support the need for further
      development of a CI-specific self-report HRQoL instrument.

PMID- 21074283
TI  - Comparison of characteristics and care-needs certification proportion between
      participants and non-participants in a geriatric health examination over a 3-year
      follow-up.
AB  - The purpose of this study was to compare the care-needs certification proportion
      of participants and non-participants in a geriatric health examination targeting
      community-dwelling seniors aged 70 years and older over 3 years. We implemented a
      geriatric health examination for 1347 community-dwelling adults aged 70 years and
      older in a local region of Japan in 2004. We followed the occurrence of new care
      needs certification for 3 years in 443 subjects who participated in the health
      examination and in the 395 non-participants. Among the 838 subjects, there were
      94 new certifications (11%) during the observation period. Non-participants had a
      significantly higher proportion of dependent, required assistance with walking
      and bathing, a history of stroke, poor self-reported health, tendency for
      depression and outdoors less than once a week than participants. Non-participants
      had a significantly lower average score of the motor fitness scale (MFS), their
      standing time from a long sitting position on the floor and the Tokyo
      Metropolitan Institute of Gerontology Index of Competence (TMIG Index of
      Competence). The proportion of care-needs certification over 3 years was
      significantly higher for non-participants (63/395, 16%) than for participants
      (31/443, 7%, p<0.05). Non-participants have a higher risk of care-needs
      certification. It is necessary to investigate current data gathering methods for
      seniors who do not undergo these examinations.

PMID- 21074284
TI  - Persistence of probiotic strains in the gastrointestinal tract when administered
      as capsules, yoghurt, or cheese.
AB  - Most clinical studies of probiotics use freeze-dried, powdered bacteria or
      bacteria packed in capsules. However, probiotics are commercially available in
      various food matrices, which may affect their persistence in the gastrointestinal
      tract. The objective of the study was to compare oral and faecal recovery during
      and after administration of a combination of Lactobacillus rhamnosus GG and
      LC705, Propionibacterium freudenreichii subsp. shermanii JS, and Bifidobacterium
      animalis subsp. lactis Bb12 as capsules, yoghurt, or cheese. This randomized,
      parallel-group, open-label trial (n=36) included a 4-week run-in, 2-week
      intervention, and 3-week follow-up period. Participants consumed 10(10)cfu/day of
      probiotic combination and provided saliva and faecal samples before, during, and
      after the intervention. Strain-specific real-time PCR was used to quantify the
      strains. L. rhamnosus GG was the only probiotic strain regularly recovered in
      saliva samples. During the intervention period it was recovered in the saliva of
      88% of the volunteers at least once. No difference was found between the yoghurt
      and cheese groups. At the end of the intervention, L. rhamnosus GG and LC705
      counts were high in faecal samples of all product groups (8.08 and 8.67log(10)
      genome copies/g, respectively). There was no matrix effect on strain quantity in
      faeces or the recovery time after ceasing the intervention. For P. freudenreichii
      subsp. shermanii JS and B. animalis subsp. lactis Bb12, a matrix effect was found
      at the end of the intervention (P<0.01 and P<0.001, respectively) and in the
      recovery time during follow-up (P<0.05 for both). Yoghurt yielded the highest
      faecal quantity of JS and Bb12 strains (8.01 and 9.89log(10) genome copies/g,
      respectively). The results showed that the administration matrix did not
      influence the faecal quantity of lactobacilli, but affected faecal counts of
      propionibacteria and bifidobacteria that were lower when consumed in cheese.
      Thus, the consumption of probiotics in yoghurt matrix is highly suitable for
      studying potential health benefits and capsules provide a comparable means of
      administration when the viability of the strain in the capsule product is
      confirmed.

PMID- 21074285
TI  - Performance characteristics of the Duopath(r) cereus enterotoxins assay for rapid
      detection of enterotoxinogenic Bacillus cereus strains.
AB  - The Duopath(r) Cereus Enterotoxins test (Merck KGaA) is a newly developed gold
      labeled lateral flow immunoassay for the detection of Bacillus cereus
      enterotoxins. The test uses monoclonal antibodies (MAbs) against the L(2)
      component of hemolysin BL (Hbl) and NheB of the non-hemolytic enterotoxin (Nhe),
      respectively. The inclusivity and exclusivity of the assay was tested using 44 B.
      cereus, B. cereus group and Bacillus spp. strains. Apart from the B. mycoides
      type strain the results were in full agreement with those obtained by other
      immunological and molecular biological methods. The detection limit of the assay
      was 6ng/ml for NheB and 20ng/ml for the Hbl-L(2)-component, respectively. Using
      artificially and naturally contaminated food samples (n=76) the assay was
      positive after 18-24h enrichment if at least 10(2) enterotoxin producing B.
      cereus/g were present. After 30h enrichment samples contaminated with as low as 1
      enterotoxin producing B. cereus/g gave positive results. In addition, testing of
      suspected colonies for enterotoxin production is possible. The assay is easy to
      perform and results can be clearly read without instrumentation.

PMID- 21074287
TI  - Mutation analysis of the FRK gene in non-small cell lung cancers.

PMID- 21074286
TI  - Use of the UKPDS Outcomes Model to predict all-cause mortality in U.S. adults
      with type 2 diabetes mellitus: comparison of predicted versus observed mortality.
AB  - AIMS: The applicability of the United Kingdom Prospective Diabetes Study (UKPDS)
      Outcomes Model is unknown in populations with type 2 diabetes mellitus (T2DM)
      outside the United Kingdom. We compared all-cause mortality predicted from the
      UKPDS model with observed mortality among T2DM subjects in the U.S. METHODS: we
      studied participants with T2DM from the National Health and Nutrition Examination
      Survey 1988-1994 with characteristics comparable to the UKPDS cohort. The 10-year
      observed all-cause mortality was compared to the UKPDS model-predicted mortality.
      The Lifetable method was used to estimate the probability of mortality for 10
      years following diagnosis. RESULTS: among 156 subjects with characteristics
      comparable to the UKPDS cohort, mean age was 49.6 years, age at T2DM diagnosis
      was 47.1 years, and T2DM duration averaged 2.6 years, with follow-up for 10.4
      years. The UKPDS model-predicted 10-year mortality was 15.7%, similar to the
      observed mortality of 14.2%. Corresponding 10-year predicted versus observed
      mortality was 32.7% versus 32.4% including subjects >age 65, 17.0% versus 19.3%
      including individuals with pre-existing CVD, and 31.1% versus 20.9% including
      individuals with diabetes duration >= 6 years. CONCLUSION: all-cause mortality
      predicted by the UKPDS model was comparable to observed mortality in U.S. NHANES
      participants with characteristics similar to the UKPDS.

PMID- 21074288
TI  - Preface to the Manufactured Nanomaterials in Subsurface Systems special issue.

PMID- 21074289
TI  - Differing contributions of LIMK and ROCK to TGFbeta-induced transcription,
      motility and invasion.
AB  - The ability of transforming growth factor beta (TGFbeta) to induce epithelial
      mesenchymal transition (EMT) is mediated by SMAD-dependent and SMAD-independent
      pathways such as the activation of Rho GTPase signalling. Upon activation, GTP
      bound Rho stimulates the ROCK kinases, which in turn phosphorylate numerous
      substrates including the LIM kinases (LIMK). The net result of ROCK activation is
      increased actin-myosin contractile force generation, with a contribution from
      LIMK-induced actin filament stabilisation. In this study, we made use of siRNA
      mediated knockdown and selective inhibitors to determine the contributions of
      ROCK and LIMK to TGFbeta-induced responses. We find that both ROCK and LIMK are
      required for TGFbeta stimulation of serum-response factor (SRF) transcriptional
      activity and actin stress fibre formation during EMT. In contrast, although LIMK
      inhibition had little effect on cell motility in scratch wound and Transwell
      migration assays, ROCK inhibition actually promoted TGFbeta-induced cell motility
      by helping individual cells to break free from the epithelial sheet. Furthermore,
      we demonstrate that selective inhibition of LIMK, but not ROCK, effectively
      blocked TGFbeta driven invasion through a layer of matrigel extracellular matrix
      protein. These results indicate that the roles of LIMK and ROCK in the Rho
      signalling pathway downstream of TGFbeta are not identical and suggest that LIMK
      represents an attractive therapeutic target in TGFbeta driven organ fibrosis and
      metastatic cancer spread.

PMID- 21074290
TI  - Analysis of OPTN as a causative gene for amyotrophic lateral sclerosis.
AB  - Mutations in the OPTN gene are well known to be associated with the development
      of glaucoma. Recently, unique variations in the same gene have been reported in
      familial and sporadic Japanese cases of amyotrophic lateral sclerosis (ALS). We
      set out to evaluate the frequency of OPTN mutations in a sample of our familial
      and sporadic ALS cohorts. All coding exons of the OPTN gene were amplified and
      sequenced in 95 unrelated familial ALS (FALS) and 95 sporadic ALS (SALS) cases of
      European descent. Two variants were newly identified in 2 individual FALS cases.
      Unique variations in the OPTN gene are rare in FALS cases and were not identified
      in any SALS patients, all of European descent.

PMID- 21074291
TI  - Assessment of activation of the plasma kallikrein-kinin system in frontal and
      temporal cortex in Alzheimer's disease and vascular dementia.
AB  - Decreased cerebral blood flow and blood-brain barrier disruption are features of
      Alzheimer's disease (AD). The plasma kallikrein-kinin system modulates
      cerebrovascular tone through release of vasoactive bradykinin (BK).
      Cerebroventricular infusion of Abeta1-40 enhances BK release, suggesting that the
      activity of this system may be elevated in AD. We investigated the profile of the
      activating protease of this system, plasma kallikrein (PK), in frontal and
      temporal brain tissue from postmortem confirmed cases of AD, vascular dementia
      (VaD), and controls. Measurements of neuron specific enolase messenger
      ribonucleic acid (mRNA) and protein were used to adjust for neuronal loss.
      Adjusted PK mRNA was significantly increased in the frontal cortex in AD, and the
      frontal and temporal cortex in VaD. Similar trends were seen for PK protein level
      in AD and VaD. PK activity was significantly increased in the frontal and
      temporal cortex in AD. Increased PK activity in AD is likely to contribute to
      increased BK release and may thereby influence cerebral blood flow and vascular
      permeability.

PMID- 21074292
TI  - [Innovative patient access schemes for the adoption of new technology: risk
      sharing agreements].
AB  - The incorporation of new treatments, procedures and technologies into the
      services' portfolio of healthcare providers should aim to improve three areas
      equally: patient access to innovative solutions, the sustainability of the health
      system and compensation for innovation. However, traditional schemes based on
      fixed prices that fail to consider the product's appropriate use or its results
      in terms of effectiveness may lead to inefficient decision-making processes.
      Recently, risk-sharing agreements have appeared as new access schemes based on
      results that aim to reduce the uncertainty of the distinct health care players
      involved in reaching an agreement on new health technology financing and
      conditions of use. Key elements in the debate on these instruments are the huge
      variety of instruments available (especially those based on results), the
      implications for different players involved in their design and supervision, and
      their possible implementation in Spain. Our main conclusion is that risk-sharing
      agreements should be used in highly limited cases when standard conditions of
      access cannot be applied due to uncertainty about long-term effectiveness. These
      measures are aimed not only at regulating price but also at acting on the
      appropriate use of new technology. However, because international experience is
      limited, drawing a solid conclusion on the final results of the application of
      risk-sharing agreements would be premature.

PMID- 21074293
TI  - [Trihalomethanes in swimming pool water in four areas of Spain participating in
      the INMA project].
AB  - OBJECTIVE: Swimming is one of the most widely practiced sports in Spain among
      people of all ages and physical conditions. This activity is also a source of
      exposure to disinfection by-products (DBP), which are potentially toxic. The DBP
      concentration in swimming pool water is not regulated and is poorly known. The
      aim of this study was to describe trihalomethane concentrations in swimming pool
      water in the municipalities of four cohorts of the INMA project. METHODS: In July
      2009, trihalomethanes were analyzed in water from 27 swimming pools in Asturias,
      Granada, Valencia and Sabadell. RESULTS: The mean total trihalomethane
      concentration was 42.7 MUg/L (standard deviation [SD]=19.1) in indoor pools and
      151.2 MUg/L (SD=80.7) in outdoor pools. In all pools, the most abundant
      trihalomethane was always chloroform. The lowest levels were found in Granada.
      CONCLUSION: Trihalomethane concentrations in swimming pool water were highly
      variable. Outdoor swimming pools showed the highest levels, which were usually
      above the legal limit for drinking water.

PMID- 21074294
TI  - Receptor-dependent (RD) 3D-QSAR approach of a series of benzylpiperidine
      inhibitors of human acetylcholinesterase (HuAChE).
AB  - Acetylcholine inhibitors (AChEIs) are currently considered as potential drugs for
      treating Alzheimer disease. In this work, we developed a receptor-dependent 3D
      QSAR (RD-3D-QSAR) models based on a series of 60 benzylpiperidine inhibitors of
      human acetylcholinesterase to support the design of new AChEIs. The best two
      models, A-F (N = 47, q(2) = 0.736, r(2) = 0.860) and C-F (N = 47, q(2) = 0.753,
      r(2) = =0.900) were developed and validated by a combined GA-PLS approach,
      available in WOLF. Residues of the aromatic gorge (Tyr341 and Trp439) and
      catalytic triad (His447) are related to both equations showing the consistency of
      these models with the SAR. Based on those models we have proposed four new
      benzylpiperidine derivatives and predicted the pIC(50) for each molecule. The
      good predicted potency of benzylpiperidine derivative, IIa, indicates that it is
      a potential candidate as a new HuAChE inhibitor.

PMID- 21074295
TI  - Synthesis, in vitro antimicrobial and in vivo antitumor evaluation of novel
      pyrimidoquinolines and its nucleoside derivatives.
AB  - Seven series of pyrimidoquinoline derivatives have been synthesized,
      tetrazolo[4',3':-1,2]pyrimido[4,5-b]quinoline (3), 2-aminopyrimido[4,5
      b]quinoline (4), triazolo[4',3':1,2]-pyrimidoquinoline (5a,b, 10),
      imidazolo[3',2':1,2]pyrimido[4,5-b]-quinoline (8a,b), 6-chloro-2
      methylthiopyrimido[4,5-b]quinoline (12), acetylated nucleosides (16, 17a,b) and
      deacetylated nucleosides (18, 19a,b). Some of the novel pyrimidoquinoline
      derivatives possess highly activity toward the bacteria and fungi species. The
      new quinolines derivatives were evaluated for their anticancer activity toward
      human cancer cell lines by the National Cancer Institute (NCI). Most of them had
      excellent growth inhibition activity, having LD(50) values in the low micromolar
      to nanomolar concentration range.

PMID- 21074296
TI  - [Manifestations and prognosis of thyrotropin-secreting pituitary adenomas: a case
      series of three patients].
AB  - INTRODUCTION: Among pituitary adenomas, thyrotropinomas were previously
      considered as extremely rare and resistant to therapy. However, the common use of
      the sensitive TSH measurement and the improvement of pituitary imaging have
      modified their clinical and hormonal presentation. CASE REPORTS: We here report
      three cases of TSH secreting pituitary adenoma that highlight the great diversity
      of the clinical, hormonal and morphological presentation, and their better
      prognosis. In the presence of an inappropriate TSH secretion, the main
      differential diagnosis is the syndrome of thyroid hormone resistance. The role of
      somatostatin analogue prior to the surgical treatment of TSH secreting pituitary
      adenoma is also underlined in this report. CONCLUSION: The increasing frequency
      and early diagnosis of TSH secreting pituitary adenoma may be explained by
      ultrasensitive methods now used for TSH measurement and progress in pituitary
      imaging, mainly with MRI. This changing spectrum in the presentation and the
      excellent response to somatostatin analogues improved in the prognosis of the
      disease.

PMID- 21074297
TI  - The role of simulation for learning within pre-registration nursing education - a
      literature review.
AB  - Simulated learning in a clinical skills centre has become more popular within
      undergraduate nursing education and is increasingly used to teach and assess
      clinical skill acquisition. Current literature suggests that there is some
      validity in teaching psychomotor skills in a designated simulated clinical skills
      centre, whilst other sources still question its value in terms of experience.
      Such contradictions demand further exploration and appraisal of the current
      literature. The findings show that simulated learning in a clinical skills
      laboratory is reported to increase student confidence and prepares students for
      real clinical setting, however, this acquisition of skill is often achieved at
      different rates by different students. A standardised approach to simulated
      learning in nursing education and the development of further holistic clinical
      scenarios which are linked to related theory and lectures, would offer measurable
      learning outcomes to meet professional and regulatory requirements. Therefore,
      further evaluation of the current learning methods within simulation may offer
      appraisal of the preparation of students for clinical practice, to ensure that
      students are offered quality-learning opportunities that are flexible and
      responsive to both their needs and the demands of the Health Care Services.

PMID- 21074298
TI  - Preceptor/mentor education: a world of possibilities through e-learning
      technology.
AB  - Preceptorship/mentorship is designed to socialize students into the nursing
      profession, promote their confidence/competence and foster their critical
      thinking ability. In today's global context, opportunities exist for local,
      rural, national and international student placements which provide exciting and
      mutually rewarding preceptorship experiences. Despite the recognized value of
      those involved in preceptorship/mentorship, however, little progress has been
      made regarding the development of an infrastructure that effectively supports
      their ongoing education. This project, piloted from October 2008 to February
      2009, leveraged our established research and teaching experience in preceptorship
      with technologies that allowed us to create an accessible and engaging e-learning
      space designed to support preceptors in a seamless fashion, improve the quality
      of the student preceptorship and enhance professional teaching capacity. A
      purposive sample of 25 preceptors was selected with a total of 18 preceptors
      successfully completing the five month program. Upon completion, participants
      were surveyed and individually interviewed. Data analysis revealed the program to
      be informative, supportive and highly valued. Knowledge derived from this study
      can: a) further enrich the substantive nature and infrastructure of online
      preceptor education; and b) contribute to clarifying best practices for preceptor
      support, facilitation, and ongoing professional development with a view to
      enhancing the preceptorship experience.

PMID- 21074299
TI  - The design and implementation of an Interactive Computerised Decision Support
      Framework (ICDSF) as a strategy to improve nursing students' clinical reasoning
      skills.
AB  - This paper describes the conceptual design and testing of an Interactive
      Computerised Decision Support Framework (ICDSF) which was constructed to enable
      student nurses to "think like a nurse." The ICDSF was based on a model of
      clinical reasoning. Teaching student nurses to reason clinically is important as
      poor clinical reasoning skills can lead to "failure-to rescue" of deteriorating
      patients. The framework of the ICDSF was based on nursing concepts to encourage
      deep learning and transferability of knowledge. The principles of active student
      participation, situated cognition to solve problems, authenticity, and cognitive
      rehearsal were used to develop the ICDSF. The ICDSF was designed in such a way
      that students moved through it in a step-wise fashion and were required to
      achieve competency at each step before proceeding to the next. The quality of the
      ICDSF was evaluated using a questionairre survey, students' written comments and
      student assessment measures on a pilot and the ICDSF. Overall students were
      highly satisfied with the clinical scenarios of the ICDSF and believed they were
      an interesting and useful way to engage in authentic clinical learning. They also
      believed the ICDSF was useful in developing cognitive skills such as clinical
      reasoning, problem-solving and decision-making. Some reported issues were the
      need for good technical support and the lack of face to face contact when using e
      learning. Some students also believed the ICDSF was less useful than actual
      clinical placements.

PMID- 21074300
TI  - Grading the performance of clinical skills: lessons to be learned from the
      performing arts.
AB  - The drift towards competency based nurse interventions has seen a growth in
      concern regarding the most appropriate methods of assessment of such
      competencies. Nurse educators and practitioners alike are struggling with the
      concept of measuring the performance of nursing skills; due to an uneasy
      relationship between competence, capability, intuition and expertise. Different
      currencies of value may be ascribed to the assessment of nursing practice,
      resulting in the use of subjective judgements together with the development of
      assessment criteria which have different weightings, depending on the values of
      the assessor. Within the performing arts, students' practice performance is also
      assessed, with seemingly many similarities between applying value to performance
      in dance or theatre and nursing. Within performing arts assessment a balancing
      act is also being played out between academic education and professional training
      (where complex performances are notoriously hard to evaluate). This paper
      explores the nature of assessment within the performing arts and makes
      suggestions regarding their application within the context of nurse education. If
      nursing is indeed a blend of art and science, then it seems sensible to look to
      the performing arts to see if lessons could be learned.

PMID- 21074302
TI  - Precision and within- and between-day variation of bioimpedance parameters in
      children aged 2-14 years.
AB  - BACKGROUND & AIMS: Bioimpedance spectroscopy (BIS) offers the possibility to
      perform rapid estimates of fluid distribution and body composition. Few studies,
      however, have addressed the precision and biological variation in a pediatric
      population. Our objectives were to evaluate precision, variation within- and
      between-days for the BIS-determined parameters total body fluid, extra-cellular
      fluid, intra-cellular fluid, body cell mass, fat-free mass, extra-cellular
      resistance, intra-cellular resistance and percentage body fat using a Xitron
      4200. METHODS: All 133 children (81 boys, 52 girls; 2.4-14.9 years) had one
      series measured on day one (precision population). Forty-four children had a
      second series on day one (within-day sub-population). Thirty-two children had a
      series measured on the next day (between-day sub-population). Each measurement
      series consisted of three repeated measurements. A linear mixed model was used
      for statistical analysis. RESULTS: The precision was 0.3-0.8% in children >=6
      years and 0.5-2.4% in children <6 years with a statistically significant
      difference between the two age-groups (p<0.001). Within-day variation was 1.1
      2.8% and between-day variation 2.4-5.7%. Total variation and reference change
      values are reported. CONCLUSION: The Xitron 4200 has a very good but age
      dependent precision. The median value of three repeated measurements is
      recommended in order to avoid incorrect measurements.

PMID- 21074303
TI  - Tracheostomy-dependent child with temporomandibular ankylosis and severe
      micrognathia treated by piezosurgery and distraction osteogenesis: case report.
AB  - Ankylosis of the temporomandibular joint in children is one the most difficult
      and complex conditions managed by oral and maxillofacial surgeons, and often
      leads to some facial deformity. Distraction osteogenesis of the mandible provides
      an excellent treatment for mandibular airway obstruction in children who do not
      respond to conservative measures, and allows for early removal of the
      tracheostomy. We report the case of a 1-year-old boy with severe micrognathia and
      temporomandibular ankylosis who was dependent on a tracheostomy; he was treated
      with piezosurgery and mandibular advancement by distraction osteogenesis.

PMID- 21074304
TI  - Cystic lesions of the jaws in edentulous patients: analysis of 27 cases.
AB  - In this retrospective study we reviewed the distribution, characteristics, and
      treatment of 27 cystic jaw lesions in edentulous patients, and compared these
      with 242 cysts in dentate patients. The mean age was 60 years (range 46-74), and
      the male:female ratio 4.4:1. The maxilla was more affected than the mandible,
      with radicular/residual cysts being the most common. Patients were treated by
      marsupialisation, enucleation, or enucleation with bone grafting. Edentulous men
      were at higher risk than women of developing cystic lesions in the maxilla.
      Patients who are edentulous alert us to the possibility that their general health
      may be compromised, and this should be kept in mind when planning treatment.

PMID- 21074305
TI  - Mandibular fractures in British military personnel secondary to blast trauma
      sustained in Iraq and Afghanistan.
AB  - Blast trauma is the primary cause of maxillofacial injury sustained by British
      service personnel on deployment, and the mandible is the maxillofacial structure
      most likely to be injured in combat, but there are few reports about the effect
      of blast trauma on it. The Joint Theatre Trauma Registry identified all
      mandibular fractures sustained by British servicemen secondary to blast injury
      between 1 January 2004 and 30 September 2009. These were matched to corresponding
      hospital notes from the Royal Centre for Defence Medicine (RCDM) for those
      evacuated servicemen and autopsy records for those who died of wounds. Seventy
      four mandibular fractures were identified in 60 servicemen. Twenty-two soldiers
      were evacuated to the RCDM and the remaining 38 died from wounds. Fractures of
      the symphysis (39/106, 37%) and body (31/106, 29%) were more common than those of
      the angle (26/106, 25%) and condyle (10/106, 9%). This pattern of injury differs
      from that of civilian blunt trauma where the condyle is the site that is injured
      most often. Those fractures thought to result from the blast wave itself usually
      caused simple localised fractures, whereas those fractures thought to result from
      fragments of the blast caused comminution that affected several areas of the
      mandible. The pattern of fractures in personnel injured while they were inside a
      vehicle resembled that traditionally seen in blunt trauma, which supports the
      requirement for mandatory wearing of seat-belts in the rear of vehicles whenever
      tactically viable. All mandibular fractures in servicemen injured while in the
      turret of a vehicle had evidence of foreign bodies or radio-opaque fragments as a
      result of their exposed position. Many of these injuries could therefore be
      potentially prevented by the adoption of facial protection.

PMID- 21074306
TI  - The role of anxiety sensitivity and drinking motives in predicting alcohol use: a
      critical review.
AB  - Anxiety sensitivity (AS) is a cognitive, individual difference variable that
      refers to the fear of arousal-related bodily sensations. Persons with high AS
      fear these sensations because they believe the sensations are signs of impending
      catastrophic events. AS has been linked to increased alcohol consumption and also
      risky drinking motives, including coping and conformity motives. This paper
      summarizes statistical modeling studies and experimental research on the
      functional relationships between AS and drinking motives and alcohol consumption.
      AS functions as a risk factor that sets the stage for negative reinforcement by
      alcohol use. Whether alcohol use becomes a method of coping with AS depends on
      multiple risk factors and motivations. We propose an integrated model to account
      for the observed relationships and to guide future research. In addition, we
      identify key methodological limitations and directions for future research.

PMID- 21074307
TI  - Mortality and business cycles by level of development: evidence from Mexico.
AB  - We investigate the relationship between mortality and business cycles within
      Mexico, where development varies significantly. We exploit this variation by
      separately analyzing the top ten and bottom ten developed states for the period
      1993-2004. We find that while overall mortality is procyclical nationally and in
      the top ten states, it is countercyclical in the bottom ten. Further, we show
      that in the top ten states mortality due to non communicable conditions is
      procyclical, while in the bottom ten mortality due to non communicable conditions
      and infectious and parasitic diseases are countercyclical. Our results suggest
      that the relationship between mortality and business cycles may vary by level of
      development.

PMID- 21074308
TI  - Evaluation of skeletal stability after surgical-orthodontic correction of
      skeletal open bite with mandibular counterclockwise rotation using modified
      inverted L osteotomy.
AB  - PURPOSE: To evaluate the surgical-orthodontic stability of treating skeletal open
      bite patients with mandibular ramus osteotomies using a modified inverted L
      osteotomy (M-ILO) and counterclockwise rotation of the mandible stabilized with
      rigid fixation. PATIENTS AND METHODS: In a retrospective review, 12 patients with
      skeletal open bites (8 females, 4 males) who received mandibular M-ILO in the
      period 2004-2007 at Tohoku University Hospital were studied. Lateral cephalograms
      were taken immediately before surgery (T1), immediately after surgery (T2), and
      at 1 yr after surgery (T3). Cephalometric analysis for point B, pogonion, menton,
      and mandibular plane angle was obtained at the designated time intervals.
      RESULTS: Mandibular counterclockwise rotation showed stability for point B,
      pogonion, and menton referred to X-Y coordinate, and for mandibular plane angle.
      The mean value for each variable was compared between T2 and T3. No statistically
      significant change was observed for all variables. CONCLUSIONS: With a well
      positioned maxilla, skeletal open bite can be successfully treated using M-ILO.
      Mandibular counterclockwise rotation showed stability at 1 yr after surgery.

PMID- 21074309
TI  - Luteinizing hormone upregulates survivin and inhibits apoptosis in ovarian
      epithelial tumors.
AB  - OBJECTIVE: Luteinizing hormone (LH) plays an important role in the development of
      ovarian cancer, and has been shown to inhibit apoptosis in ovarian cancer cells.
      Similarly, survivin is a molecule that has been shown to inhibit apoptosis in
      other types of cancer. Therefore, the aim of this study was to determine whether
      survivin can be induced by LH in ovarian cancer, and whether this induction
      influences the sensitivity of ovarian cancers to chemotherapy. STUDY DESIGN:
      Survivin expression was monitored using western blot assays, and flow cytometry
      was used to detect the effects of cisplatin on the induction of apoptosis by LH.
      MTT assays were also used to analyze rates of cell proliferation. RESULTS:
      Administration of LH in vitro induced survivin expression in a dose-dependent
      manner. Moreover, this signaling was dependent on the ERK1/2 signaling pathway.
      LH also blocked apoptosis induced by cisplatin. CONCLUSION: These results suggest
      that LH influences the sensitivity of ovarian cancer cells to chemotherapy via
      signaling to inhibit apoptosis that also upregulates survivin.

PMID- 21074310
TI  - Challenges in the transvaginal management of abnormal uterine bleeding secondary
      to cesarean section scar defect.
AB  - OBJECTIVE: Research suggests that the resectoscopic management of abnormal
      uterine bleeding (AUB) following cesarean section (CS) is safe and effective.
      There is, however, a lack of complementary data from routine clinical practice.
      We aimed to evaluate the efficacy of resectoscopic remodeling of the CS scar in
      the management of post CS AUB (pCSAUB). STUDY DESIGN: The case notes of 57 women
      with pCSAUB who had undergone a resectoscopic remodeling procedure were reviewed
      retrospectively. Primary outcome measures were the duration of preoperative and
      postoperative menstruation, and postoperative menstrual change. Secondary outcome
      measures were the impact of patient-dependent variables on the success of the
      resectoscopic remodeling procedure. The CS scar was located using transvaginal
      ultrasonography and hysteroscopy. The remodeling procedure was performed with a
      hysteroscopic resectoscope, and commenced with resection of the fibromuscular
      scar. This started at the roof of the scar pouch and progressed towards the
      external os. It then continued along a line parallel to the axis of the cervical
      canal. The exposed dilated blood vessels and endometrial-like tissue in the roof
      of the remaining pouch were electrocauterized with a roller-ball electrode.
      RESULTS: The mean operating time was 30.2 +/- 6.6 min. There was a significant
      difference in the mean duration of preoperative and postoperative menstruation
      (12.9 +/- 2.9 days and 9.4 +/- 4.1 days, respectively; p < 0.001). However, only
      59.6% of patients (34/57) reported a postoperative improvement in symptoms. A
      significant postoperative improvement was observed more frequently in patients
      with anteflexed uteri than in patients with retroflexed uteri, and this
      difference was significant (90.6% (29/32) and 20.0% (5/25), respectively; p <
      0.001). No correlations were found between treatment outcome and age, body
      weight, parity, number of cesarean deliveries, duration of preoperative
      menstruation, or operating time. CONCLUSIONS: Resectoscopic uterine remodeling is
      an appropriate therapy in patients with pCSAUB and an anteflexed uterus.

PMID- 21074311
TI  - Maternal circulating osteoprotegerin and soluble RANKL in pre-eclamptic women.
AB  - OBJECTIVE: To evaluate alterations in the concentrations of osteoprotegerin
      (OPG), RANKL and the OPG/RANKL ratio in pre-eclamptic women during the
      puerperium. STUDY DESIGN: This cross-sectional study was performed in the
      maternity ward of Aretaieio Hospital in Athens, Greece. Fifteen pregnant women
      with severe pre-eclampsia and 15 matched controls with premature rupture of the
      membranes were recruited. Fasting blood samples were obtained antepartum,
      immediately after diagnosing pre-eclampsia (median: 32nd gestational week), and
      during the 3rd-6th day postpartum, to estimate levels of circulating OPG and
      RANKL as well as the OPG/RANKL ratio. The anthropometric parameters evaluated
      included body mass index and blood pressure. RESULTS: Mean circulating OPG levels
      decreased significantly in both groups in the postpartum period (controls: 43.7
      +/- 19.1 ng/ml vs 22.9 +/- 9.1 ng/ml, p = 0.008; pre-eclamptic group: 72.3 +/-
      49.9 vs 49.7 +/- 40.9 ng/ml, p = 0.002). The antepartum OPG/RANKL ratio was
      elevated in hypertensive pregnancies (2.41 +/- 1.72) compared to normotensive
      pregnancies (1.45 +/- 0.63), but the difference did not reach statistical
      significance (p = 0.1). The OPG/RANKL ratio decreased in the control group (0.76
      +/- 0.30, NS) following delivery, while it remained unchanged in the pre
      eclamptic women (1.63 +/- 1.40, p = 0.13). Consequently, the postpartum OPG/RANKL
      ratio was significantly higher in the pre-eclamptic women compared to control
      women (1.63 +/- 1.40 vs 0.76 +/- 0.30, p = 0.01). Levels of RANKL demonstrated no
      significant alterations during puerperium in both cases. CONCLUSION: Pregnancies
      complicated with pre-eclampsia exhibit higher OPG levels and OPG/RANKL ratios,
      compared to control pregnancies, which might be compatible with lower bone
      turnover. The significance of this finding with respect to bone metabolism
      remains to be elucidated in larger studies.

PMID- 21074312
TI  - Short- and long-term effects of ammonium and nitrite on the Anammox process.
AB  - Autotrophic anaerobic ammonium oxidation (Anammox) is a biological process in
      which Planctomycete-type bacteria combine ammonium and nitrite to generate
      nitrogen gas. Both substrates can exert inhibitory effects on the process,
      causing the decrease of the specific activity of the biomass and the loss of the
      stable operation of reactors. The aim of the present work is to evaluate these
      effects in short- and long-term experiments. The short-term effects were carried
      out with two different types of Anammox biomass, biofilm on inorganic carriers
      and flocculent sludge. The effects of ammonium on both kinds of biomass were
      similar. A decrease of the Specific Anammox Activity (SAA) of 50% was observed at
      concentrations about 38 mg NH(3)-N.L(-1), while 100 mg NH(3)-N.L(-1) caused an
      inhibition of 80%. With regards to nitrite, the SAA was not affected at
      concentrations up to 6.6 MUg HNO(2)-N.L(-1) but it suffered a decrease over 50%
      in the presence of 11 MUg HNO(2)-N.L(-1) in the case of the biofilm. The
      flocculent biomass was much less resistant and its SAA sharply decreased up to
      30% of its initial value in the presence of 4.4 MUg HNO(2)-N.L(-1). The study of
      the long-term effects was carried out in lab-scale Sequencing Batch Reactors
      (SBR) inoculated with the biofilm biomass. Concentrations up to 20 mg NH(3)-N.L(
      1) showed no effects on either reactor efficiency or biomass activity. However,
      when free ammonia concentrations reached values between 35 and 40 mg NH(3)-N.L(
      1), the operation turned unstable and the efficiency was totally lost. Nitrous
      acid concentrations around 1.5 MUg HNO(2)-N.L(-1) caused a loss of the efficiency
      of the treatment and a destabilization of the system. However, a total
      restoration of the SAA was observed after the stoichiometric feeding was applied
      to the SBR.

PMID- 21074313
TI  - Charcoal production in a UK moorland wildfire--how important is it?
AB  - Wildfires are a common feature of peatland environments, but the carbon balance
      of these wildfires is often not considered and the production of refractory black
      carbon in these wildfires could be an important addition to carbon accumulation
      and mitigate losses of biomass during the fire. This study investigates the
      biomass and carbon losses during a moorland wildfire. Changes in above-ground
      carbon stocks were calculated using a combination of field data, laboratory
      measurements and literature values. The results show that approximately 14% of
      the carbon in the original above-ground biomass remained on the site after the
      burn. Black carbon production was approximately 6 gC m(-2) which constituted 4.3%
      of the biomass lost. The survival of biomass and black carbon may help to
      mitigate the loss of carbon during the fire.

PMID- 21074314
TI  - Reflexive assessment of practical and holistic sanitation development tools using
      the rural and peri-urban case of Mexico.
AB  - Lack of sanitation affects the lives of billions of people worldwide. It is now
      generally agreed that sustainable solutions to this complex problem require
      social and cultural factors to be addressed in addition to the habitual economic
      and technical aspects. Increasingly, sector professionals view the fragmented
      approaches to sanitation as a limiting factor. This refers to the fragmentation
      of the knowledge on the subject among often hermetic disciplines and to the
      distribution of political mandates on sanitation across many institutions, which
      independently tackle specific aspects of the issue. Holistic approaches have
      often been suggested as a solution. This paper presents the development of such a
      holistic approach, designed to assess sanitation development in rural and peri
      urban settings. Tested in three Mexican communities, it relies on qualitative
      research tools to identify critical influences to sanitation development. This
      article presents generic results about micro and macro-factors affecting
      sanitation development in Mexican villages, and reflexively examines the research
      process as well as the strengths and limitations of the approach. The conceptual
      map developed for each case study successfully highlights the interconnectedness
      of all factors affecting sanitation development. Despite some weaknesses, these
      maps constitute a practical assessment tool for interdisciplinary teams deployed
      in integrated water and sanitation development programs and a valuable didactic
      tool for training activities.

PMID- 21074315
TI  - Coal-burning roasted corn and chili as the cause of dental fluorosis for children
      in southwestern China.
AB  - To find the pathologic cause of the children's dental fluorosis in southwestern
      China, diet structure before the age of 6 and prevalence rate of dental fluorosis
      (DF) of 405 children were investigated, and the fluorine and arsenic content of
      several materials were determined. The prevalence rate of DF of children living
      on roasted corn before the age of 6 is 100% with nearly 95% having the mild to
      severe DF; while that of children living on non-roasted corn or rice is less than
      5% with all having very mild DF. The average fluorine and arsenic concentration
      are 20.26 mg/kg and 0.249 mg/kg in roasted corn, which are about 16 times and 35
      times more than in non-roasted corn, respectively. The average fluorine
      concentration is 78 mg/kg in coal, 1116 mg/kg in binder clay and 313 mg/kg in
      briquette (coal mixed with clay). The average arsenic concentration of coal is
      5.83 mg/kg, the binder clay is 20.94 mg/kg, with 8.52 mg/kg in the briquette.
      Living on roasted corn and chili is the main pathologic cause of endemic
      fluorosis in southwestern China. The main source of fluorine and arsenic
      pollution of roasted corn and chill is the briquette of coal and binder clay.

PMID- 21074316
TI  - Trace metal contents in barbeque (BBQ) charcoal products.
AB  - In this study, the concentrations of trace elements contained in solid barbeque
      (BBQ) charcoal products have been investigated. Eleven brands of charcoal
      products were analyzed, consisting of both Korean (3 types) and imported products
      (eight types from three countries) commonly available in the Korean market
      places. The concentrations of trace metals in solid charcoal varied widely across
      metal types and between samples with the overall range of 5 MUg kg(-1) (As) to
      118 mg kg(-1) (Zn). The patterns of metal distribution between different products
      appeared to be affected by the properties of raw materials and/or the processes
      involved in their production. Although concentrations of certain trace metals
      were significantly high in certain charcoal samples, their emission
      concentrations were below legislative guidelines (e.g., the permissible exposure
      limit (PEL) set by the Occupational Safety and Health Administration (OSHA)). In
      light of the potential harm of grilling activities, proper regulation should be
      considered to control the use of BBQ charcoal from a toxicological viewpoint to
      help reduce the potential health risks associated with its use.

PMID- 21074317
TI  - Phytotoxic effects of nickel on yield and concentration of macro- and micro
      nutrients in sunflower (Helianthus annuus L.) achenes.
AB  - The phytotoxic effects of varying levels of nickel (0, 10, 20, 30, and 40 mg L(
      1)) on growth, yield and accumulation of macro- and micro-nutrients in leaves and
      achenes of sunflower (Helianthus annuus L.) were appraised in this study. A
      marked reduction in root and shoot fresh biomass was recorded at higher Ni
      levels. Nickel stress also caused a substantial decrease in all macro- and micro
      nutrients in leaves and achenes. The lower level of Ni (10 mg L(-1)) had a non
      significant effect on various yield attributes, but higher Ni levels considerably
      decreased these parameters. Higher Ni levels decreased the concentrations of Ca,
      Mn and Fe in achenes. In contrast, achene N, K, Zn, Mn and Cu decreased
      consistently with increasing level of Ni, even at lower level (10 mg L(-1)).
      Sunflower hybrid Hysun-33 had better yield and higher most of the nutrients in
      achenes as compared with SF-187. The maximum reduction in all parameters was
      observed at the maximum level of nickel (40 mg L(-1)) where almost all parameters
      were reduced more than 50% of those of control plants. In conclusion, the pattern
      of uptake and accumulation of different nutrients in sunflower plants were
      nutrient- and cultivar-specific under Ni-stress.

PMID- 21074318
TI  - Cd(II) and As(III) bioaccumulation by recombinant Escherichia coli expressing
      oligomeric human metallothioneins.
AB  - Metallothioneins (MTs) are a family of metal binding proteins. Recombinant
      Escherichia coli expressing the human MT (hMT-1A) gene was constructed for
      bioaccumulation of heavy metals. In order to increase protein stability, the
      glutathione S-transferase (GST) gene was fused with the hMT-1A gene and
      coexpressed. In order to increase MT expression efficiency and metal binding
      capacity, two, three or four hMT-1A genes were integrated in series and
      overexpressed in E. coli. The recombinant E. coli expressing the GST fused
      trimeric hMT-1A protein exhibited the highest Cd(II) and As(III) bioaccumulation
      ability, 6.36 mg Cd/g dry cells and 7.59 mg As/g dry cells, respectively.

PMID- 21074319
TI  - Removal of fluoride from drinking water using aluminum hydroxide coated rice husk
      ash.
AB  - Fluoride content in groundwater that is greater than the WHO limit of 1.5mg/L,
      causes dental and skeletal fluorosis. In India, several states are affected with
      excess fluoride in groundwater. The problem is aggravated due to the lack of
      appropriate and user friendly defluoridation technology. Several fluoride removal
      techniques are reported in the literature amongst which the Nalgonda technique
      and use of activated alumina have been studied extensively. However a simple,
      efficient and cost effective technology is not available for widespread use in
      many affected regions. In this paper, we present a novel cost effective
      defluoridation method that is based on surface modification of rice husk ash
      (RHA) by coating aluminum hydroxide. RHA is obtained by burning rice/paddy husk
      which is an abundantly available and is an inexpensive raw material. The results
      showed excellent fluoride removal efficiency and the adsorption capacity was
      found to be between 9 and 10mg/g.

PMID- 21074320
TI  - Comparative study on the catalytic electrooxidative abilities of RuO(x)-PdO
      TiO(2)/Ti and RuO(x)-PdO/Ti anode.
AB  - Comparative study of the catalytic electrooxidative abilities of RuO(x)-PdO/Ti
      and RuO(x)-PdO-TiO(2)/Ti were conducted using Active Orange 5R solution as
      simulated wastewater. RuO(x)-PdO-TiO(2)/Ti anode possesses higher catalytic
      oxidation ability, as compared to RuO(x)-PdO/Ti, in both direct oxidation and
      indirect oxidation processes. RuO(x)-PdO-TiO(2)/Ti could provide a discoloration
      rate of 98.14% within 30 min, while the COD removal could reach 51.43% in 120
      min. It was indicated that higher electrooxidation ability could be achieved at
      RuO(x)-PdO-TiO(2)/Ti anode, which exhibited lower chlorine evolution potential
      and higher oxygen evolution potential probably resulted from the higher oxidation
      states of Ru and Pd.

PMID- 21074321
TI  - Alumina coated with oxazolone derivative for extraction of trace amounts of
      cadmium and copper from water and plant samples.
AB  - A solid phase extraction procedure is proposed for simultaneous separation and
      preconcentration trace amounts of Cu(II) and Cd(II) using alumina coated with N'
      {4-[4-{1-[4-(dimethylamino)phenyl]methylidene}-5-(4-H)oxazolone]phenyle}acetamide
      and determination by flame atomic absorption spectrometry. Using 0.1g of the
      sorbent, the metal ions were sorbed at pH 7 and recovered with 5.0 mL of 0.5 mol
      L(-1) HNO(3). It was found that extraction can be performed from the sample
      volumes of 2000 and 800 mL for Cu and Cd, respectively (preconcentration factors
      of 400 for Cu and 160 for Cd). Obtained sorption capacities for 1g sorbent were 8
      mg Cu and 14 mg Cd. The linearity was maintained in the concentration range of
      0.1 ng mL(-1) to 7.0 MUg mL(-1) for Cu and 0.13 ng mL(-1) to 2.0 MUg mL(-1) for
      Cd in the original solution. Eight replicate determinations of a mixture
      containing 1.0 MUg mL(-1) each of the elements in the final solution gave
      relative standard deviation +/-1.6 and +/-1.3% for Cu and Cd, respectively. The
      detection limit was calculated as 0.06 and 0.05 ng mL(-1) for Cu and Cd,
      respectively. The proposed method was successfully applied to the determination
      trace amounts of Cu and Cd in the water and plant samples.

PMID- 21074322
TI  - Decreasing polycyclic aromatic hydrocarbons emission from bitumen using
      alternative bitumen production process.
AB  - In 1988, the National Institute for Occupational Safety and Health (NIOSH)
      recommended that bitumen fumes should also be considered a potential occupational
      carcinogen and management practices such as engineering controls should be
      implemented. Changing the production process of bitumen, as a source control
      method, was investigated in our study. For the first time, a novel alternative
      process was used to produce paving grade bitumen with decreased PAH emissions as
      well as improved bitumen performance grade (PG). Post-consumer latex and natural
      bitumen (NB) were used as additives to obtain 60/70 modified bitumen directly
      from the vacuum bottom (VB) without any need for air-blowing. The emissions were
      produced by a laboratory fume generation rig and were sampled and analyzed by GC
      Mass and GC-FID as described in NIOSH method 5515. The PG of the resulting
      modified 60/70 bitumen in this study covers a wider range of climatic conditions
      and has higher total resistance against deformation than conventional 60/70
      bitumen. The total PAH emissions from modified 60/70 bitumen (100.2619 ng/g) were
      decreased approximately to 50% of PAHs emitted from conventional 60/70 bitumen
      (197.696 ng/g). Therefore, it is possible to obtain modified bitumen with lower
      PAH emissions and better quality than conventional bitumen via additives and
      without air-blowing.

PMID- 21074323
TI  - Hepatic profile of Gallus gallus Linnaeus, 1758 experimentally infected by
      Plasmodium juxtanucleare Versiani & Gomes, 1941.
AB  - One of the species that causes avian malaria is Plasmodium juxtanucleare. It is
      commonly found in poultry, especially when the birds receive food free of
      coccidiostats. Since industrial and organic poultry breeding is increasing in the
      world and few studies have been conducted examining the clinical parameters of
      both healthy and infected birds, this work evaluated whether the infection caused
      by P. juxtanucleare in Gallus gallus provokes alterations in the birds' hepatic
      profile. We analyzed the activity of ALT and AST and carried out histological
      analyses of liver sections of infected fowls by intracelomic inoculation with
      infected blood from a donor fowl with a parasite load of around 7%. The infected
      birds' parasite load was evaluated during 45 days by means of blood smears. There
      was a positive correlation between the increase in parasite load and higher ALT
      activity in the infected fowls, but there was no significant variation of the AST
      activity between the control and infected groups, possibly because of the non
      specificity of this enzyme as an indicator of hepatic lesion. The results show
      that infection caused by P. juxtanucleare in G. gallus provokes hepatic
      alterations, indicated by the increase in the ALT enzyme activity and by the
      inflammatory infiltrates found in the liver sections of the infected fowls.

PMID- 21074324
TI  - High prevalence of Sarcocystis calchasi sporocysts in European Accipiter hawks.
AB  - The emerging Sarcocystis calchasi induces a severe and lethal central nervous
      disease in its intermediate host, the domestic pigeon (Columba livia f.
      domestica). Experimental studies have identified the Northern goshawk (Accipiter
      g. gentilis) as final host. Phylogenetically closely related European
      sparrowhawks (Accipiter n. nisus) and wood pigeons (Columba palumbus) have been
      found to harbor genetically closely related Sarcocystis spp. However, data on the
      prevalence and potential interspecies occurrence of these parasites are lacking.
      Here, we report that European Accipiter hawks (Accipitrinae) are highly infected
      with S. calchasi, S. columbae and Sarcocystis sp. ex A. nisus in their small
      intestine. Thirty-one of 50 (62%) Northern goshawks necropsied during 1997-2008
      were positive for S. calchasi in a newly established species-specific semi-nested
      PCR assay based on the first internal transcribed spacer region. Unexpectedly, 14
      of 20 (71.4%) European sparrowhawks tested also positive. In addition, birds of
      both species were found to be infested with S. columbae and an, as yet, unnamed
      Sarcocystis sp. recently isolated from European sparrowhawks. These findings
      raise new questions about the host specificity of S. calchasi and its high
      virulence in domestic pigeons, since sparrowhawks only rarely prey on pigeons.
      Notably, isolated sporocysts from both infected Accipiter spp. measured 8 MUm *
      11.9 MUm, precluding a preliminary identification of S. calchasi in feces of
      Accipiter hawks based on morphology alone. Importantly, three of four Northern
      goshawks used in falconry tested positive for S. calchasi. In conclusion, the
      results indicate that both European Accipter spp. in Germany serve as natural
      final hosts of S. calchasi and suggest that falconry and pigeon sport may serve
      as risk factors for the spread of this pathogen in domestic pigeons.

PMID- 21074325
TI  - Immune response to Neospora caninum native antigens formulated with immune
      stimulating complexes in calves.
AB  - The aim of this study was to compare the immune responses to live Neospora
      caninum tachyzoites and N. caninum native antigens formulated with immune
      stimulating complexes matrix (ISCOM-matrix) in calves. Fifteen calves were used
      in this study: 3 were intravenously inoculated with 1 * 10(8) live tachyzoites
      (Group A), 3 were inoculated twice with N. caninum native antigens formulated
      with ISCOMs (Group B); 3 with N. caninum native antigens in phosphate-buffered
      saline (PBS) (Group C); 3 received ISCOM-matrix (ISCOMs without antigen) (Group
      D) and 3 were negative controls receiving PBS (Group E). The last four groups
      were inoculated subcutaneously. The specific total IgG and its subtypes were
      analyzed by an indirect enzyme-linked immunosorbent assays (ELISAs) and by
      Western blot. IFN-gamma levels in plasma was quantified using a commercial kit.
      All calves were challenged intravenously with 1 * 10(8) live tachyzoites at week
      11 after receiving the first dose. Parasitemia was assessed in plasma samples by
      semi-nested PCR. Neospora-specific antibodies were detected in animals from
      Groups A and B in the week 2 after inoculation. The ELISA OD values were higher
      in Group B compared with Group A from weeks 6 to 11 (P<0.05). Analysis of the
      subisotype specific antibodies in experimentally infected calves revealed a
      predominant IgG(2) response; however, a predominant IgG(1) response was observed
      in animals inoculated with N. caninum native antigens formulated with ISCOM
      matrix. Control calves remained seronegative until challenge infection. The
      pattern of bands by Western blot was similar when testing sera from animals in
      Groups A and B. The levels of IFN-gamma production after respective immunization
      schedules were similar between Groups A and B. Neospora-DNA was detected in
      plasma samples shortly after intravenous challenge in calves from all groups
      including those receiving the experimental vaccine formulation. The duration of
      the parasitemia was similar in all groups.

PMID- 21074326
TI  - Prevalence and molecular characterization of bovine coenurosis from Eastern
      Anatolian region of Turkey.
AB  - This study was conducted to determine the prevalence and molecular
      characteristics of Coenurus cerebralis, the metacestode of Taenia multiceps in
      cattle from Erzurum province located in eastern region of Turkey between November
      2009 and April 2010. Five of 1045 brains of cattle (0.47%) were found to be
      infected with Coenurus cysts. The characteristics and morphology of C. cerebralis
      were seen in all the cysts. The cyts from three infected cattle were genetically
      analyzed and confirmed to be T. multiceps metacestodes by NAD1 and COX1
      mitochondrial gene sequence analysis. Pairwise comparison between the NAD1
      sequences of the T. multiceps isolates from Erzurum and other T. multiceps
      isolates available in GenBank showed differences ranging from 0.6 to 2.9%, while
      COX1 sequences showed differences ranging from 0.2 to 2.6%. Considering the two
      genes, it was seen that all of the three isolates from Erzurum province were in
      the same group according to phylogenetic analyses. The present findings could
      provide a stimulus for future studies on the systematic relationships and
      epidemiology of lesser-known taeniid cestodes in the region, employing
      mitochondrial sequence data sets.

PMID- 21074327
TI  - A simplified method for hatching and isolating Toxocara canis larvae to
      facilitate excretory-secretory antigen collection in vitro.
AB  - Human toxocariasis causes several dangerous syndromes that can involve the
      viscera, vision and central nervous system. Diagnosing toxocariasis requires the
      identification of antibodies against Toxocara canis or Toxocara cati excretions
      and secretions (ES). To obtain ES it is necessary to collect a large number of
      larvae. However, since the earliest work describing the culture of Toxocara
      larvae, few advances in the method have been made. It has been suggested that
      carbon dioxide triggers molecular mechanisms that enable nematode hatching. A
      similar hypothesis has been made regarding Giardia excystation. To test the
      hypothesis we used the Giardia excystation HBSS method to hatch embryonated T.
      canis eggs. We found that the HBSS method was more effective than the original De
      Savigny method. Our results suggest that both parasites require stimulation in an
      acidic environment, and the abrupt change to a basic milieu in duodenum. This
      physiological adaptation is successful to exploit the intestinal habitat.

PMID- 21074328
TI  - Negative effect of the arthropod parasite, Sarcoptes scabiei, on testes mass in
      Iberian ibex, Capra pyrenaica.
AB  - Testes mass is a key factor in male reproductive success and is potentially
      exposed to so-called 'parasitic castration'. This is the result of the direct
      destruction or alteration of reproductive cell lineages (parasitic castration
      sensu stricto), or the indirect detrimental effects - for example, via body
      condition - on the ability of progenitors to produce or rear offspring (parasitic
      castration sensu lato). There are enormous gaps in our knowledge on the effects
      of parasites on the testes of wild mammals and in an attempt to rectify this
      dearth of data we examined the relationship between the skin parasite Sarcoptes
      scabiei and testes mass in Iberian ibex Capra pyrenaica. We considered data from
      222 males that were culled in the population from the Sierra Nevada in Spain. Our
      results provide evidence that sarcoptic mange is associated with reduced size
      corrected testes mass in Iberian ibex which supports the hypothesis that
      parasitism is a determining factor in gonad plasticity in male mammals. We
      discuss several hypothetical causes of this relationship and highlight the need
      to deepen the sub-lethal effects of pathogens if we are to accurately understand
      their modulator effects on host population dynamics.

PMID- 21074329
TI  - Electrical injury alters ion channel expression levels and electrophysiological
      properties in rabbit dorsal root ganglia neurons.
AB  - The electrophysiological and morphological changes of nerve fibers induced by
      electrical injury have been widely addressed. However, the changes of ion
      channels in neurons after electrical shocks have not been systematically
      investigated yet. In this study, the sciatic nerves of rabbit were injured by 50
      V 50 Hz, 110 V 50 Hz, and 220 V 50 Hz alternating current, respectively. One week
      later, the expression levels and electrophysiological changes of voltage-gated
      potassium (Kv) and sodium (Nav) channels in dorsal root ganglia (DRG) neurons
      were evaluated by RT-PCR, immunofluorescence staining and patch clamp technique.
      The Nav1.1 expression was decreased by 50V injury. The Kv1.2, Kv1.4, Nav1.1 and
      Nav1.7 expression levels and Kv current densities were reduced after 110 V
      injury. Under the 220 V injury circumstance, Kv1.2, Nav1.1, Nav1.7 expression
      levels, Kv current densities and TTX-R Na(+) current densities were significantly
      decreased, while TTX-S Na(+) current densities increased. These findings suggest
      that the expression levels, subunit compositions, and electrophysiological
      properties of Kv and Nav channels are altered after electrical injury, and the
      severity of injury gets worse as injury voltage increases.

PMID- 21074330
TI  - Effect of training in the Emergency Management of Severe Burns on the knowledge
      and performance of emergency care workers as measured by an online simulated burn
      incident.
AB  - OBJECTIVE: To determine the value of training for the Emergency Management of
      Severe Burns (EMSB) for medical and nursing staff working in emergency care as
      measured by their performance in a simulated burn incident online program.
      METHODS: An Internet-based questionnaire, which included a simulated burn
      incident, was developed. All of the medical and nursing staff in hospital
      emergency departments and ambulance services in the Netherlands were invited to
      complete this questionnaire. The effect of EMSB training on the individual's
      knowledge of and performance in the emergency management of a burn victim was
      evaluated because some of the respondents had participated in EMSB training,
      whereas others had not. RESULTS: Of the 280 responses received, 198
      questionnaires were included in the analysis. The analyzed questionnaires were
      submitted by nurses (43%), ambulance workers (33%), and physicians (23%). Only
      14% of the people in the study had participated in EMSB training, whereas 78% had
      received other or additional life support training and 22% of respondents had no
      additional life support training. Medical and nursing staff who had participated
      in EMSB training performed better in the following subjects: mentioning
      hypothermia as a focus of attention (70% versus 53%, p=0.085), correct use of
      hand size (70% versus 36%, p=0.001) and use of the correct hand percentage in the
      estimation of total body surface area (TBSA, 82% versus 57%, p=0.015), suspicion
      of no airway obstruction in an outdoor trauma (93% versus 63%, p = 0.002) and
      referral of functional area burns to a burn center (22% versus 8%, p = 0.04).
      However, both groups overestimated the TBSA (34% of the total group overestimated
      >= 20%) and did not know the correct formula for fluid resuscitation (87% of the
      total group). CONCLUSION: There is some evidence that medical staff members who
      have participated in EMSB training have a better knowledge of emergency
      management and are more effective in the management of a simulated burn case.
      However, both individuals who had participated in EMSB as well as those who had
      not participated in EMSB needed additional training in EMSB.

PMID- 21074331
TI  - Licking as an out-of-hospital burns treatment-An isolated cultural phenomenon?
AB  - Wound management in burns is a potentially complex issue. Salivary constituents
      have been shown experimentally to be of benefit in the treatment of thermal
      injuries. In our clinical experience we have encountered patients who have saliva
      directly applied to the burn wound prior to presenting to the national burns
      service. The practice is known as "Licking". We report two cases to illustrate
      the presentations we have encountered. We believe that these illustrate an
      isolated phenomenon unique to the Republic of Ireland.

PMID- 21074332
TI  - End of life decisions and care of the adult burn patient.
AB  - INTRODUCTION: Despite advancements in the provision of burn care, there is still
      a significant cohort of patients who fail to respond to therapy or for whom
      treatment is deemed futile. The decision to withdraw support from, or to
      implement a Do-Not-Resuscitate (DNAR) order in, such patients can be challenging.
      Our aims were to review the withdrawal of life-sustaining treatment, issuing of
      DNAR orders and end of life care in burn patient deaths. METHODS: A retrospective
      case notes review was undertaken, for all burn in-patient deaths from 1st April
      2001 to 31st December 2007. RESULTS: Following exclusions, 63 patients were
      included in our study, with a median age of 56 years (21-94). End of life
      decisions in younger patients (under 65 years) were more often due to burn
      severity. In those over 65 years, reasons were due to co-morbidities, and these
      decisions were made late in the patient's admission. In 34% of patients, end of
      life care was not comprehensively documented. CONCLUSION: A coherent, decisive
      approach should be adopted and adhered to by all members of the multi
      disciplinary team, with clear, standardised documentation in place.

PMID- 21074333
TI  - Cortisol responses to serial MRI scans in healthy adults and in depression.
AB  - Magnetic resonance imaging (MRI) scans are a novel environment for most
      participants. The hypothalamic-pituitary-adrenal (HPA) axis modulates
      neurohormonal responses to novel and stressful experiences. We sought to examine
      the neurohormonal responses to MRI scans with the measurement of salivary
      cortisol. We examined: (1) acute effects of MRI scans by acquiring cortisol
      measurements immediately preceding and following the scan in comparison with
      basal cortisol levels, and (2) effects of novelty by measuring cortisol during
      repeated MRI scans in the same subjects. We examined these effects in two groups
      of subjects: healthy individuals (n=27, mean age 41.6 years) and patients with
      depression (n=24, mean age 40.0 years). Both groups showed elevated cortisol
      levels immediately preceding the MRI scan, particularly for the initial MRI scan,
      which normalised after the follow up MRI scans as compared with mean basal
      cortisol levels. There were no significant differences in the acute or mean basal
      cortisol levels between the groups. In summary, the MRI experience is stressful,
      particularly for the initial scan, but the stress response is reduced with
      subsequent scans.

PMID- 21074334
TI  - Successful implementation of image-guided radiation therapy quality assurance in
      the Trans Tasman Radiation Oncology Group 08.01 PROFIT Study.
AB  - PURPOSE: The quality assurance (QA) of image-guided radiation therapy (IGRT)
      within clinical trials is in its infancy, but its importance will continue to
      grow as IGRT becomes the standard of care. The purpose of this study was to
      demonstrate the feasibility of IGRT QA as part of the credentialing process for a
      clinical trial. METHODS AND MATERIALS: As part of the accreditation process for a
      randomized trial in prostate cancer hypofraction, IGRT benchmarking across
      multiple sites was incorporated. Each participating site underwent IGRT
      credentialing via a site visit. In all centers, intraprostatic fiducials were
      used. A real-time assessment of analysis of IGRT was performed using Varian's
      Offline Review image analysis package. Two-dimensional (2D) kV and MV electronic
      portal imaging prostate patient datasets were used, consisting of 39 treatment
      verification images for 2D/2D comparison with the digitally reconstructed
      radiograph derived from the planning scan. The influence of differing sites,
      image modality, and observer experience on IGRT was then assessed. RESULTS:
      Statistical analysis of the mean mismatch errors showed that IGRT analysis was
      performed uniformly regardless of institution, therapist seniority, or imaging
      modality across the three orthogonal planes. CONCLUSIONS: The IGRT component of
      clinical trials that include sophisticated planning and treatment protocols must
      undergo stringent QA. The IGRT technique of intraprostatic fiducials has been
      shown in the context of this trial to be undertaken in a uniform manner across
      Australia. Extending this concept to many sites with different equipment and IGRT
      experience will require a robust remote credentialing process.

PMID- 21074335
TI  - Irradiation of spinal metastases: should we continue to include one uninvolved
      vertebral body above and below in the radiation field?
AB  - PURPOSE: Historically, the appropriate target volume to be irradiated for spinal
      metastases is 1-2 vertebral bodies above and below the level of involvement for
      three reasons: (1) to avoid missing the correct level in the absence of
      simulation or (2) to account for the possibility of spread of disease to the
      adjacent level, and (3) to account for beam penumbra. In this study, we
      hypothesized that isolated failures occurring in the level adjacent to level
      treated with stereotactic body radiosurgery (SBRS) were infrequent and that with
      improved localization techniques with image-guided radiation therapy, treatment
      of only the involved level of spinal metastases may be more appropriate. METHODS
      AND MATERIALS: Patients who had received SBRS treatments to only the involved
      level of the spine as part of a prospective trial for spinal metastases comprised
      the study population. Follow-up imaging with spine MRI was performed at 3-month
      intervals following initial treatment. Failures in the adjacent (V+/-1, V+/-2)
      and distant spine were identified and classified accordingly. RESULTS: Fifty
      eight patients met inclusion criteria for this study and harbored 65 distinct
      spinal metastases. At 18-month median follow-up, seven (10.7%) patients failed
      simultaneously at adjacent levels V+/-1 and at multiple sites throughout the
      spine. Only two (3%) patients experienced isolated, solitary adjacent failures at
      9 and 11 months, respectively. CONCLUSION: Isolated local failures of the
      unirradiated adjacent vertebral bodies may occur in <5% of patients with isolated
      spinal metastasis. On the basis of the data, the current practice of irradiating
      one vertebral body above and below seems unnecessary and could be revised to
      irradiate only the involved level(s) of the spine metastasis.

PMID- 21074336
TI  - [Hormonal treatment in breast cancer].
AB  - The discovery of breast cancer carcinoma sensitivity to estradiol (E) suppression
      is the starting point of hormonal treatment. Hormonal receptors (ER and PR) are
      the pathway of the action of estradiol on breast tumor cells. The detection of at
      least one of these two receptors is needed to classify a tumor as hormone
      sensitive. The hormonal treatment of breast cancer attempts to suppress the
      stimulating action of E on tumor cells. This can be done by decreasing E
      synthesis--ovarian suppression (OS) or aromatase inhibitors (AIs)--or by
      compelling with E on receptors--tamoxifen (TAM). In advanced breast cancer,
      hormonal treatment gives good response with few side effects. In young patient,
      the treatment is based on TAM. It could be associated with OS. In post-menopausal
      women, AIs are more potent than TAM. They are used in the first line treatment
      and TAM as a second line. Fulvestrant is not superior TAM or AIs. In the adjuvant
      setting, hormonal treatment gives a significant reduction of recurrence and
      death. In young patient, the treatment is based on TAM. It could be associated
      with OS. In post-menopausal patients, adjuvant treatment must include an AIs for
      at least one part of the treatment. A survey of bone density is necessary.

PMID- 21074337
TI  - An azole-resistant isolate of Malassezia pachydermatis.
AB  - Canine Malassezia dermatitis (MD) is frequently treated with systemic
      ketoconazole (KTZ) and itaconazole (ITZ). However, the antifungal susceptibility
      of clinical isolates of M. pachydermatis from dogs and cats to the azoles has not
      been well investigated. In the present study, the in vitro susceptibility of the
      standard strain (CBS1879: the neotype strain of M. pachydermatis) and 29 clinical
      isolates of M. pachydermatis to the azoles was measured by a modified CLSI M27-A2
      test using modified Dixon medium as well as by the E-test. The minimum inhibitory
      concentrations (MICs) of the 30 isolates of M. pachydermatis (including the
      neotype strain) against KTZ and ITZ were <0.03 MUg/ml by the two methods. The
      MICs of 1 clinical isolate (ASC-11) were 1 and 2 MUg/ml against KTZ, and 2 and 8
      MUg/ml against ITZ, by the modified CLSI M27-A2 test and the E-test,
      respectively. Thus, isolate ASC-11 may be resistant to these azoles, making this
      the first report of a resistant isolate of M. pachydermatis to KTZ and ITZ.

PMID- 21074338
TI  - FSH is superior to eCG for promoting ovarian response in Chinese Bamei gilts.
AB  - The Bamei gilt is a Chinese native breed located in northwest China, which adapts
      to the extremely dry and cold environment and is distinguished for its excellent
      reproductive and maternal characters. To ensure sufficient numbers of embryos for
      transgenic and nuclear transfer research, hormonal induction of gilt estrus and
      superovulation may be necessary. The objective of this study was to compare the
      superovulation effects of equine chorionic gonadotropin (eCG, Group A) and FSH
      (Groups B-D) in Chinese Bamei gilts. The results show that though eCG could
      produce more corpora lutea (CL, 14.3) than the control (CL, 9.2), and the FSH
      treatments had significantly increased the number of CL compared with the eCG
      treatment. Within the different FSH protocols, the numbers of CL were
      significantly greater in Groups B (CL, 77.8) and C (CL, 66.8) than in Group D
      (CL, 42.7), however, ovarian cysts were observed in Groups B and C, but not in
      Group D. These data suggest that Group D (280 IU FSH) is a suitable protocol to
      facilitate the development of ovarian follicles and increase the number of useful
      embryos per gilt for embryos recovery. The optimal FSH protocol of superovulation
      in Bamei gilts appears to be: D13/100 IU, D14/80 IU, D15/60 IU, D16/40 IU plus
      prostaglandin (PG) 0.2mg, D17/hCG 1000 IU.

PMID- 21074339
TI  - Lack of sufficient information on the specificity and selectivity of commercial
      phytoestrogens preparations for therapeutic purposes.
AB  - Phytoestrogens (PEs) are polyphenols of plant origin among which flavones,
      flavanones, isoflavones, coumarins, chalcones, lignans and stilbenes are the best
      representatives. By interacting with specific residues of the estradiol-binding
      pocket of estrogen receptors (ERs), they induce estrogenic responses, supporting
      the concept that they could be of benefits against the menopausal disorders due
      to endogenous estradiol depletion. According to literature data, PEs target a
      panel of proteins, suggesting that their effects are not limited to ER-dependent
      transcription pathways. In this regard, commercial preparations usually contain a
      mixture of compounds of which nature and concentration are not specified. Such
      mixtures being freely accessible and escaping thereby medical survey, they could
      exert unwanted effects, depending on their qualitative and quantitative
      composition as well as the physiopathological status of the women. This work
      outlines the necessity to inform consumers of the exact nature of these PEs
      preparations. Moreover, women who want to take PEs should inform their
      practitioner to be under strict medical survey. In the case of hormone-dependent
      cancer antecedents or predispositions, use of PEs is extremely inadvisable.

PMID- 21074340
TI  - Four novel alkyl 2-cyanoacylate monomers and their use in latent fingermark
      detection by mid-infrared spectral imaging.
AB  - Four novel alkyl 2-cyanoacrylate monomers (alkyl=1-cyanoethyl, 2-cyanoethyl,
      trideuteromethyl and pentadeuteroethyl) have been tested for their ability to
      develop latent fingermarks that can then be visualized using mid-infrared
      spectral (chemical) imaging. Each of the four monomers was chosen for its
      potential to produce a strong, isolated infrared spectral band in its
      corresponding polymer (to provide spectral contrast against most backgrounds), as
      well as for its potential ability to be fumed onto fingermarks in the manner of
      conventional ethyl 2-cyanoacrylate (superglue). With the exception of the 2
      cyanoethyl 2-cyanoacrylate, which had to be fumed under reduced pressure, all of
      the monomers were found to be sufficiently volatile to be fumed in a conventional
      fuming cabinet. All four monomers polymerized selectively on fingermark ridges on
      a variety of non-porous and semi-porous surfaces, leading to excellent
      development of the fingermarks. Unfortunately, although high quality mid-infrared
      spectral images of the fingermarks could be formed for all of the polymers at
      various frequencies, the new CN or CD stretching vibrations did not give rise to
      strong enough absorption intensities for good contrast on difficult backgrounds
      such as polymer banknotes. However, in the 1-cyanoethyl 2-cyanoacrylate polymer,
      the presence of the additional nitrile group had the unintended but desirable
      effect of shifting the strong CO absorption to higher frequencies, moving it away
      from interfering banknote absorptions. This enabled fingermark contrast to be
      achieved even against the intaglio printing on the banknotes.

PMID- 21074342
TI  - A rare case of mantle cell lymphoma as  lymphomatous polyposis with widespread 
      involvement of the digestive tract.
AB  - Lymphomatous polyposis of the gastrointestinal tract is rare. It refers to a
      heterogeneous group of small B-cell lymphomas including mantle cell lymphoma,
      follicular lymphoma and MALT lymphoma. It is characterized by the presence of
      multiple lymphomatous polyps along one or more segments of the digestive tract.
      Clinical symptoms are non-specific. We herein report the case of a 74-year old
      man initially admitted for an upper and lower gastrointestinal endoscopy to
      explore a positive Hemoccult test. The endoscopy revealed multiple polyps all
      along the gastrointestinal tract. Histopathological study showed a diffuse
      lymphomatous proliferation of small B-cells whose immunohistochemical features
      were compatible with a mantle cell lymphoma. Tumoral B-cells showed a positivity
      of cyclin D1 markers but negativity for CD5. Immunochemotherapy with R-CHOP
      (rituximab, cyclophosphamide, adriamycine, vincristine and prednisone) was
      initiated. Based on this case study, the pitfalls of gastrointestinal tract
      lymphomatous polyposis diagnosis, prognosis and treatment options are discussed.

PMID- 21074343
TI  - Femoroacetabular cam-type impingement: diagnostic sensitivity and specificity of
      radiographic views compared to radial MRI.
AB  - PURPOSE: To retrospectively assess the diagnostic sensitivity of 45 degrees  Dunn
      view and cross-table lateral radiographs for the assessment of cam deformity by
      comparison with radial MRI. MATERIALS AND METHODS: 60 cases with radiographs (38
      a-p and 45 degrees  Dunn views, 22 a-p and cross-table lateral views) and radial
      MRI were assessed. Alpha angle measurements were obtained both for radiographs
      and radial MRI. Statistics included frequency analysis, bivariate linear
      correlation analyses of MRI and radiograph measurements and cross-table analyses
      testing for the sensitivity and specificity of radiographs for the detection of
      an alpha angle larger than 55 degrees . RESULTS: 53.3% had the maximum alpha
      angle in the superior-anterior aspect of the femoral head-neck junction. Cam
      deformity was found in 45/60 cases (75%) in radial MRI. Pearson correlation
      demonstrated the Dunn view was most accurate for the superior-anterior aspect
      (.772, P<.001). The cross-table lateral views were best suited for the anterior
      superior aspect (.511, P<.05). The sensitivity for cam deformity in the Dunn view
      was 96.4% vs. 70.6% in the cross-table lateral view. CONCLUSION: The 45 degrees 
      Dunn view can improve the first line of impingement diagnostics. Radial MRI
      however remains indispensable for pre-operative planning and the evaluation of
      symptomatic cases without obvious deformity.

PMID- 21074344
TI  - Interobserver variation in reporting CT arthrograms of the shoulder.
AB  - Computed tomography (CT) arthrography of the shoulder is an imaging modality of
      great diagnostic accuracy with regard to glenohumeral instability and in
      particular labral lesions. Interpretation of the scans is made difficult by the
      frequent occurrence of normal anatomic variants and the complexity of injuries to
      the bone and soft tissues. We selected a continuous sample of 50 CT arthrograms
      of the shoulder and they were reported by two consultant musculoskeletal
      radiologists. The results were collated and analysed for the level of agreement.
      Hill-Sachs showed Kappa (K) statistic to be 0.37 (fair agreement), soft tissue
      Bankart 0.32 (fair agreement), bony Bankart 0.61 (substantial agreement),
      anterior capsular laxity 0.41 (moderate agreement) and glenohumeral
      osteoarthritis 0.20 (slight agreement). All the results were significant with a p
      value of <0.05. Nine (18%) of the 50 scans were in complete agreement. The
      results demonstrate that there can be considerable interobserver variation (IOV)
      in the reports of a CT arthrogram of a shoulder. They highlight the potential
      difficulties in reporting such images and suggests ways in which the report could
      be more focussed to provide a clinically reliable report and one which matches
      the surgical findings accurately.

PMID- 21074345
TI  - Automated vessel segmentation using cross-correlation and pooled covariance
      matrix analysis.
AB  - Time-resolved contrast-enhanced magnetic resonance angiography (CE-MRA) provides
      contrast dynamics in the vasculature and allows vessel segmentation based on
      temporal correlation analysis. Here we present an automated vessel segmentation
      algorithm including automated generation of regions of interest (ROIs), cross
      correlation and pooled sample covariance matrix analysis. The dynamic images are
      divided into multiple equal-sized regions. In each region, ROIs for artery, vein
      and background are generated using an iterative thresholding algorithm based on
      the contrast arrival time map and contrast enhancement map. Region-specific multi
      feature cross-correlation analysis and pooled covariance matrix analysis are
      performed to calculate the Mahalanobis distances (MDs), which are used to
      automatically separate arteries from veins. This segmentation algorithm is
      applied to a dual-phase dynamic imaging acquisition scheme where low-resolution
      time-resolved images are acquired during the dynamic phase followed by high
      frequency data acquisition at the steady-state phase. The segmented low
      resolution arterial and venous images are then combined with the high-frequency
      data in k-space and inverse Fourier transformed to form the final segmented
      arterial and venous images. Results from volunteer and patient studies
      demonstrate the advantages of this automated vessel segmentation and dual phase
      data acquisition technique.

PMID- 21074346
TI  - Quantification of N-acetyl-seryl-aspartyl-lysyl-proline in hemodialysis patients
      administered angiotensin-converting enzyme inhibitors by stable isotope dilution
      liquid chromatography-tandem mass spectrometry.
AB  - We developed a sensitive, selective and accurate method based on liquid
      chromatography with tandem mass spectrometry (LC-MS/MS) to determine N-terminal
      thymosin-beta peptides of Ac-SDKP and Ac-ADKP in human plasma samples.
      Quantification of Ac-SDKP and Ac-ADKP was performed using solid phase extraction
      (SPE) based on C(18), reversed phase LC separation, and stable isotope dilution
      electrospray ionization-MS/MS in multiple reaction-monitoring (MRM) mode. The Ac
      SDKP-(13)C(6), (15)N(2) and Ac-ADKP-d(7) were synthesized for the internal
      standards. These MRM monitoring ions were m/z 488->129 (quantitative ion)/226 for
      Ac-SDKP, m/z 496->137 for Ac-SDKP-(13)C(6), (15)N(2), m/z 472->129 (quantitative
      ion)/226 for Ac-ADKP, and m/z 479->129 for Ac-ADKP-d(7), respectively. Lower
      limit of quantitation (LLOQ) of Ac-SDKP and Ac-ADKP was 0.1ng/mL in human plasma.
      Recovery values were ranged from 94.7% to 106.3% for inter- (RSD: 0.6-3.5%) and
      intra- (RSD: 0.4-4.9%) day assays. Plasma Ac-SDKP levels were significantly
      higher in hemodialyzed subjects treated with angiotensin-converting enzyme
      inhibitors of enalapril (27.3+/-24.6ng/mL, n=10) and trandolapril (12.3+/
      16.9ng/mL, n=18) than healthy (0.4+/-0.2ng/mL, n=7) and hemodialyzed subjects
      (0.6+/-0.2ng/mL, n=34). This analytical method would be useful to measure N
      terminal thymosin-beta peptides in human plasma for the clinical study.

PMID- 21074347
TI  - Inequality of access to breast reconstruction.

PMID- 21074348
TI  - [Clinical usefulness of circulating ECD/HER-2 measurement for breast cancer
      patients' management].
AB  - BACKGROUND: About 15 to 20% of breast cancer cases overexpress human epidermal
      growth factor receptor-2 (HER-2). This overexpression is associated with poor
      clinical prognosis but therapeutic success of trastuzumab or lapatinib. HER-2
      extracellular domain (ECD) undergoes a proteolytic cleavage and is shed into
      biologic fluid as a circulating antigen called ECD/HER-2, which can be detected
      by immunochemical assays. OBJECTIVE: The aim of our review was to determine the
      clinical usefulness of ECD/HER-2 measurement in the management of breast cancer
      patients. MATERIAL AND METHODS: A Pubmed search for publications in English or
      French was carried out until March 31, 2010 (69 original articles and 8 reviews).
      RESULTS: The measurement of ECD/HER-2 concentration does not exempt from the
      pathological determination of HER-2 expression in tumors; some HER-2 negative
      tumors are associated with high levels of ECD/HER-2, on the other hand, some HER
      2 positive tumors present low levels of ECD/HER-2. The concentration of ECD/HER-2
      is correlated to disease progression, since 10% of loco-regional breast cancers
      and more than a third of metastatic breast cancers have high levels of ECD/HER-2.
      The elevation of ECD/HER-2 levels generally occurs several months before the
      diagnosis of symptomatic metastases. The relevance of ECD/HER-2 measurements
      during chemotherapy, hormone therapy and trastuzumab treatment remains uncertain.
      Similarly, it is not commonly agreed that high levels of ECD/HER-2 before any
      treatment in the case of an early breast cancer, is an independent prognostic
      factor. DISCUSSION: A close analysis of a variety of pathological, biochemical,
      clinical and methodological data may explain these discrepancies. CONCLUSION: New
      prospective studies using immunochemical measurements of ECD/HER-2 (with a
      consensual threshold) and based on both detailed pathological analyses and a
      comprehensive collection of clinical data are still required to establish the
      clinical usefulness of circulating ECD/HER-2 measurement for breast cancer
      patients' management.

PMID- 21074349
TI  - [Localized cystic lymphatic malformation (or cutaneous lymphangiomas)].
AB  - Cutaneous cystic lymphatic malformations consist of dilatations of various sizes,
      developed from the lymphatic system. Various clinical presentations exist, which
      are more or less complex and severe. MRI is the best examination to determine the
      extent of deep lesions. Therapeutic decisions usually follow multidisciplinary
      consultations. In localized superficial forms, whether surgical excision or
      abstention is required. In macrocystic forms, sclerotherapy is the first-line
      treatment.

PMID- 21074350
TI  - [Predictors of functional decline of older persons after an hospitalisation in an
      acute care for elder unit: importance of recent functional evolution].
AB  - OBJECTIVES: To identify the predictors of functional decline of older persons
      after hospitalization in an Acute Care for Elder unit (ACE). METHODS:
      Retrospective observational study based on a population hospitalised in ACE unit
      in Grenoble University Hospital. Dead patients within hospitalisation and patient
      fully disable or already hospitalized 15 days before hospitalisation were
      excluded. The primary outcome was the functional decline defined by a loss in
      activity daily life (ADL) between discharge and 15 days before hospitalisation.
      The predictive factors included socio-demographic data, geriatric assessment and
      the admission pathway. RESULTS: 184 patients were included (mean 86.4+/-6.2
      years, 64.1% women). The admission by emergency department was predominant
      (77.2%). The mean length of stay was 16.0+/-9.5 days. A functional decline as
      present for 31.0% des patients; for 95% of these patients, the functional decline
      occurred before admission to ACE. Factors associated with functional decline at
      discharge were: recent functional decline, ADL level at admission, pressure sore,
      denutrition and admission via the emergency room (ER) (p<0.05). In the
      multivariate analysis, recent functional decline was strongly associated with
      functional decline at discharge (OR=58.8, p<0.01). Outside this factor, ADL level
      at admission (OR=3.2, p<0.01), hypoalbuminemaia (OR=2.6, p=0.01) and an admission
      via the ER (OR=2.6, p=0.05) were independently associated with functional decline
      at discharge. CONCLUSION: Better management of hospitalised older persons,
      according to the ACE model, has diminished the negative functional effects of
      hospitalization. Identification of recent functional decline rather than other
      usually identified predictors would be useful for detection of older patients who
      might benefit from a geriatric program. Detecting and correcting early
      malnutrition and developing direct admissions mechanisms may improve functional
      prognosis of hospitalised older patients.

PMID- 21074351
TI  - [Orthopaedic manifestations of Von Recklinghausen's neurofibromatosis].
AB  - OBJECTIVE: Von Recklinghausen's neurofibromatosis is a dominant autosomic genetic
      disease characterized by different clinical manifestations. The goal of this work
      was to study its orthopaedic manifestations and to show the characteristics of
      their management. METHOD: A retrospective study was carried out on 15 patients
      having a Von Recklinghausen's neurofibromatosis. For each patient, different
      orthopaedic manifestations and their evolution after treatment were analyzed.
      These manifestations were classified in spinal deformities, pseudarthrosis of
      long bones and tumours of the peripheral nerves. RESULTS: The spinal deformities
      were observed in 9 cases. A dystrophic scoliosis was observed in 6 patients with
      an average angle of 50 degrees  and was associated to a kyphosis in 5 patients.
      The treatment was surgical by posterior arthrodesis in 2 cases and
      circumferential arthrodesis in 2 cases. The congenital curves and pseudarthroses
      of leg were observed in 5 cases, localized at the lower third of the leg in all
      cases. An Ilizarov external fixator with segmental osseous transport was carried
      out in 2 patients. The duration of the external fixator was 23 months 1/2 with 5
      interventions in each case. Four plexiform neurofibromas and 3 nodular
      neurofibromas were observed. A transformation into neurofibrosarcoma was found in
      2 patients. In one case, a resection without functional sacrifice was carried out
      and in the other case the patient was dead before the resection. CONCLUSION: The
      orthopaedic manifestations of Von Recklinghausen's neurofibromatosis are
      frequent, varied and have a difficult management. The functional and sometimes
      vital prognoses are challenging.

PMID- 21074352
TI  - [Chemotherapy in gallbladder carcinoma].
AB  - Gallbladder cancer is an aggressive tumor. Its incidence varies according to
      geography. Surgery is the standard treatment for localized stage but there is no
      standard treatment in metastatic or locally advanced disease. Because of the
      rarity of bile tract cancer (BTC) and gallblader carcinoma (GBC), most studies
      have grouped all BTC and GBC together, and there are very few GBC-specific
      studies. In addition, there is a paucity of randomized controlled studies in this
      disease with small numbers of patients and inclusion bias. One randomized trial
      ABC-02 was well conducted and showed a survival benefit in favor of gemcitabine
      (GEM)+cisplatin (CDDP), which can be regarded as the standard in locally advanced
      BTC. Adjuvant therapy after surgical resection is not validated. Understanding
      the molecular mechanisms of carcinogenesis of GBC has opened the way for the use
      of targeted therapies. This new treatment would improve survival and quality of
      life of our patients.

PMID- 21074353
TI  - The spectrum of imaging findings of brucellosis: a pictorial essay.

PMID- 21074354
TI  - Iliac artery pseudoaneurysm rupture following excision of an infected hip
      prosthesis.
AB  - We report a case of external iliac artery aneurysm rupture during removal of the
      acetabular component for septic loosening. Potentially fatal hemorrhage would
      have occurred if the risk had not been recognized, and the external iliac vessels
      exposed to gain vascular control before proceeding with implant removal. A review
      of the literature on vascular injury at revision hip surgery is presented.

PMID- 21074355
TI  - Improved clinical outcomes after high-flexion total knee arthroplasty: a 5-year
      follow-up study.
AB  - The purpose of this study was to determine if high-flexion total knee
      arthroplasty resulted in improved outcomes compared with conventional total knee
      arthroplasty. This was a prospective, double-blind, randomized controlled trial
      involving 76 patients over 5 years. We compared the postoperative flexion range,
      Knee Society scores, Oxford knee scores, and SF-36 scores between 2 groups. The
      high-flexion group was able to achieve a significant sustainable increase in
      postoperative knee flexion angle; and this correlated to a significant
      improvement in the General Health, Vitality, and Physical Functioning scales of
      SF-36 at 5 years postoperatively. Our results signify that high-flexion total
      knee arthroplasty has additional benefits to the quality of life in patients who
      require higher degrees of knee flexion in their activities of daily living.

PMID- 21074356
TI  - Factors that impact expectations before total knee arthroplasty.
AB  - This study examined the effect of patient attributes on expectations before total
      knee arthroplasty (TKA). A total of 1943 patients completed an Expectations
      Survey before TKA. Demographics, surgical history, baseline Medical Outcomes
      Study Short Form 36 (SF-36) score, Knee injury and Osteoarthritis Outcome Score
      (KOOS), and Lower Extremity Activity Scale score were obtained. On univariate
      analysis, expectations (mean score, 77.6) correlated with SF-36 General Health,
      age, SF-36 Vitality, KOOS Quality-of-Life, and Lower Extremity Activity Scale.
      Living alone and history of joint arthroplasty were associated with significantly
      lower expectations, whereas male sex and white race were associated with higher
      expectations. On multivariate regression analysis, age, living situation, history
      of joint arthroplasty, SF-36 General Health, and KOOS Quality-of-Life remained
      significant predictors of expectations. Our results suggest that high, possibly
      unrealistic, expectations of TKA are common and should be moderated to maintain
      patient satisfaction.

PMID- 21074357
TI  - High-flexion vs conventional prostheses total knee arthroplasty: a meta-analysis.
AB  - Whether high-flexion prostheses are superior to conventional prostheses after
      total knee arthroplasty (TKA) remains controversial. Therefore, this meta
      analysis was conducted to evaluate the effects of these 2 different designs.
      After a comprehensive search, 11 trials with 1204 knees were eligible for data
      extraction and pooled analysis. The results demonstrated that there were no
      differences in range of motion of high-flexion posterior-stabilized vs standard
      posterior-stabilized TKA (weighted mean improvement, 0.93 degrees ; 95%
      confidence intervals, -0.75 degrees  to 2.60 degrees ; P = .28), range of motion
      of high-flexion cruciate-retaining vs cruciate-retaining TKA (2.06 degrees ; 0.06
      degrees -4.17 degrees ; P = .06), weight-bearing flexion (2.05 degrees ; 0.99
      degrees -5.08 degrees ; P = .19), Knee Society Scores (1.59 points; 0.42-3.60
      points; P = .12), and Hospital for Special Surgery Scores (0.84 points; 0.37-2.04
      points; P = .17) with at least 1-year follow-up. No infection, loosening, and
      osteolysis were found. The current evidences cannot confirm that high-flexion
      prostheses are superior to conventional prostheses.

PMID- 21074358
TI  - The Stanmore knee arthrodesis prosthesis.
AB  - Knee arthrodesis is most commonly performed for failed total knee arthroplasty.
      Conventional arthrodesis techniques are associated with a high incidence of
      complications and are unsuitable in cases with extensive bone loss. We report our
      medium-term results using a custom-made cemented knee arthrodesis prosthesis in
      10 patients with a mean follow-up of 56.4 months (range, 15-199 months). The
      prosthesis was implanted as a 1- or 2-stage procedure for infected revision knee
      arthroplasty or tumor endoprosthesis in 9 patients and as a primary procedure in
      1 patient with angiosarcoma involving the knee extensor mechanism. The average
      combined femoral and tibial bone deficit was 170 mm (range, 56-220 mm). Implant
      survivorship was 90%. All patients with retained prosthesis had no evidence of
      residual infection or loosening and were able to mobilize independently. One
      prosthesis was revised though retained following a prosthetic fracture, and 1
      patient underwent above-knee amputation for uncontrolled infection. We conclude
      that the Stanmore knee arthrodesis prosthesis provides reliable fusion in an
      otherwise difficult-to-treat group of patients.

PMID- 21074359
TI  - Quality of assessment of randomized controlled trials in blood conservation after
      joint arthroplasty.
AB  - Blood transfusion after joint arthroplasty occurs in up to two thirds of
      patients. We conducted a systematic review of the literature to determine the
      methodological quality of published randomized controlled trials (RCTs). We
      searched MEDLINE, EMBASE, and Cochrane to identify RCTs in arthroplasty with
      blood conservation as the primary outcome from 2001 to 2007. Methodological
      quality was evaluated using the Detsky index. We identified 62 RCTs. The mean
      Detsky score was 73% +/- 14%. Epidemiology affiliation (P = .003), funding
      support (<.001), and year of publication (<.001) were the predictors of reporting
      quality, predicting 46% of the variability (R(2) = 0.46). This suggests poor
      reporting quality of trials in blood conservation. The inclusion of an
      epidemiologist or a biostatistician for the design of a trial is strongly
      recommended.

PMID- 21074360
TI  - New model of mapping difficulties in solving analogical problems among
      adolescents and adults with intellectual disability.
AB  - The main goal of the study was to map the difficulties and cognitive processes
      among adolescents (aged 13-21, N = 30) and adults (aged 25-66, N = 30) with mild
      and moderate intellectual disability (ID) when solving analogical problems. The
      participants were administered the Conceptual and Perceptual Analogical
      Modifiability test. A three-fold tailored dynamic assessment (DA) model for
      mapping difficulties was constructed based on Sternberg's analogical components
      model (encoding, inference, mapping, application): (a) mapping pre-teaching
      difficulties; (b) assessing the level of mediation; and (c) analyzing post
      teaching responses. Another goal was to find out whether participants receiving
      "tailored" mediation would receive higher scores than participants receiving the
      standard DA procedure (adolescents aged 14-20; N = 30) and adults (25-55, N =
      31). Repeated measures MANOVA of time * age * ID level indicated significant pre
      to post-teaching improvement across all age groups and ID levels. The adults
      gained more from mediation than the adolescents. The tailored DA model was more
      effective in producing change than the standard DA model. The greatest
      difficulties in the pre-teaching stage were in inference and mapping of
      perceptual analogies, where the participants received the highest level of
      mediation. Stepwise regression analysis indicated that inference, ID level and
      age predicted modifiability in the application of conceptual analogies, whereas
      encoding, ID level and mediation for inference predicted modifiability in the
      application of perceptual analogies.

PMID- 21074361
TI  - "Flap valve phenomenon" limiting aortic regurgitation in prosthetic valve
      dehiscence.
AB  - The authors describe the case of a 52-year-old man with a history of supra
      annular mechanical aortic valve replacement who presented with fever and
      abdominal pain. He was found to have an abdominal wall abscess. Subsequent
      transesophageal echocardiography revealed dehiscence of his mechanical aortic
      valve, supporting a diagnosis of prosthetic valve endocarditis. Transesophageal
      echocardiography demonstrated that the dehisced aortic valve rocked on a hinge
      point, mimicking the motion of a flap valve. As the prosthetic valve rose with
      systole, it permitted flow into the aorta and, falling back in diastole, formed
      enough of a seal against the wall of the aortic annulus to limit aortic
      insufficiency. This "flap valve phenomenon" resulted in minimal perivalvular
      regurgitation, and the patient remained hemodynamically stable without heart
      failure before valve replacement.

PMID- 21074362
TI  - Usefulness of a new miniaturized echocardiographic system in outpatient
      cardiology consultations as an extension of physical examination.
AB  - BACKGROUND: The aim of this study was to assess the usefulness of a new
      miniaturized echocardiographic system (MS) to perform bedside echocardiography in
      initial outpatient cardiology consultations, in addition to physical examination.
      METHODS: One hundred eighty-nine patients referred for initial cardiology
      outpatient consultations at two tertiary hospitals in two countries were studied.
      Each patient was submitted to physical examination followed by MS assessment.
      Scanning time, the number of examinations with abnormal results after physical
      examination and the MS, and the information obtained by physical examination
      alone and followed by the MS (in terms of its importance in reaching a diagnosis,
      in the necessity of performing routine echocardiography, and in the decision to
      release the patient from the outpatient clinic) were assessed. RESULTS: The
      scanning time with the MS was 180 +/- 86 seconds. Its use after physical
      examination led to diagnoses in 141 patients (74.6%) and to an additional 37
      patients (19.6%) being released from the outpatient clinic. After physical
      examination followed by MS assessment, only 64 patients (33.9%) were sent to the
      echocardiography lab. The MS modified the decision of whether to send a patient
      to the echocardiography lab, with referral determined by the MS in 27 patients
      (14.3%) and no referral determined by the MS in 58 patients (30.7%). CONCLUSIONS:
      The new MS caused a negligible increase in the duration of consultations. It
      showed additive clinical value over physical examination, increasing the number
      of diagnoses, reducing the use of unnecessary routine echocardiography,
      increasing the number of adequate echocardiographic studies, and determining a
      large number of releases from the outpatient clinic.

PMID- 21074363
TI  - On the syntax of left ventricular hypertrophy: eschew obfuscation, espouse
      elucidation.

PMID- 21074364
TI  - Left ventricular torsion by two-dimensional speckle tracking echocardiography in
      patient with a-type amyloid heart disease.
AB  - Amyloidosis is a clinical disorder caused by extracellular and or intracellular
      deposition of insoluble abnormal amyloid fibrils that alter the normal function
      of tissues. Amyloid A amyloidosis is the most common form of systemic amyloidosis
      worldwide The heart may be affected in systemic AL amyloidosis, but also more
      rarely in A amyloidosis. In this report, we presented a patient with A-type
      amyloid heart disease who had dynamic left ventricular outflow tract obstruction
      mimicking hypertrophic obstructive cardiomyopathy. We also investigated left
      ventricular torsion, untwisting rate and left ventricular longitudinal global
      strain by two-dimensional speckle tracking echocardiography.

PMID- 21074365
TI  - Systolic right ventricular function in pediatric and adolescent patients with
      tetralogy of Fallot: echocardiography versus magnetic resonance imaging.
AB  - OBJECTIVE: The tricuspid annular plane systolic excursion (TAPSE) as an
      echocardiographic index to assess right ventricular (RV) systolic function has
      not been investigated thoroughly in pediatric patients and adolescents with
      tetralogy of Fallot (TOF) after surgical repair. METHODS: TAPSE was determined in
      131 patients with TOF and 252 age-matched normal subjects. TAPSE values were
      compared with RV ejection fraction (EF) and indexed RV end-diastolic volume
      (EDVi) determined by magnetic resonance imaging in a cross-sectional study
      design. TAPSE values were also correlated to QRS duration (QRSd) determined by
      electrocardiogram. RESULTS: The TAPSE values showed a positive correlation with
      age in normal subjects. The TAPSE was not decreased in infants and young children
      with TOF compared with normal subjects. A significant reduction of TAPSE values
      with increasing time after surgical repair was observed. After a mean of 7 years
      after surgical repair, the TAPSE values become significantly reduced compared
      with age-matched controls, being below the lower bound of -2 standard deviations.
      A positive correlation between TAPSE with RVEF and a negative correlation between
      TAPSE with RVEDVi were observed. A significant positive correlation was found
      between QRSd and RVEDVi, and a significant negative correlation was found between
      QRSd and RVEF. CONCLUSION: Although TAPSE was initially preserved, impaired TAPSE
      was observed with increasing time after surgical repair in pediatric patients
      with TOF.

PMID- 21074366
TI  - Enhanced 3D curvature pattern and melanoma diagnosis.
AB  - This article describes an enhanced curvature pattern based melanoma diagnosis
      system using convolution techniques and ensemble classifiers. We extract the 3D
      data of melanoma with a photometric stereo device first. Then differential forms
      of the melanoma surface can be extracted with the convolution method proposed.
      After extracting 3D based differential forms, statistical moments of enhanced
      principal curvatures of skin surfaces are calculated to describe the geometrical
      texture patterns. Finally, ensemble classifiers are constructed whose optimal
      mean sensitivity and specificity can reach 89.24 percent and 87.62 percent
      respectively. Comparisons with skin tilt/slant pattern based 3D shape
      characterization method and 2D methods like color variation and border
      irregularity are also included.

PMID- 21074367
TI  - Reproducibility of volumetric measurements on maxillary sinuses.
AB  - Although computer assisted volumetric quantification of human maxillary sinuses
      is commonly used to measure volumetric changes during life, reliability data for
      this procedure are lacking. The objective of this retrospective study is to test
      a semi-automatic virtual volumetric analysis technique on 36 CT scans of human
      maxillary sinuses. Three examiners with different clinical experience performed
      all measurements in three replicates. As principle of proof, the technique was
      examined on 12 phantoms with known volumes. The validation of the method revealed
      that the mean relative error was 0.364%. For the retrospective volumetric
      measurements from maxillary sinuses the intra- and inter-examiner agreement was
      quantified using appropriate intraclass correlation coefficients (ICC 1,k and ICC
      2,k) and the Bland-Altman analysis. ICC values ranging from 0.997 to 0.999
      indicate almost perfect agreement for intra- and inter-examiner data. The Bland
      Altman analysis demonstrated good intra- as well as inter-examiner agreement for
      the two proficient examiners and a lack of agreement for the untrained examiner.
      It can be concluded that this measurement procedure using CT scans could be
      strongly recommended for clinical application to determine the volume of human
      maxillary sinuses reliably.

PMID- 21074368
TI  - The influence of orthognathic surgery on ventilation during sleep.
AB  - Orthognathic surgery has varying effects on respiratory parameters. The authors
      undertook a prospective study of patients requiring mandibular advancement,
      mandibular setback and maxillary Le Fort I advancement, and surgically assisted
      rapid maxillary expansion (SARME). Breathing parameters were monitored in a sleep
      laboratory the night before the operation and in a mean of 9.5 months after the
      operation. In patients treated with mandibular advancement, the respiratory
      disturbance index (RDI), oxygen desaturation index (ODI), and number of
      obstructive apnoeas (OAs) improved significantly. In patients treated with
      mandibular setback and maxillary Le Fort I advancement, the RDI, ODI, index of
      flow limitations (IFL), number of obstructive hypopnoeas (OHs), OA, and oxygen
      saturation deteriorated. In contrast, patients treated with SARME improved only
      mildly. These results indicate that bimaxillary surgery for Class III
      malocclusion increased upper airway resistance, probably because of a more dorsal
      positioning of the base of the tongue, representing an iatrogenic obstructive
      sleep apnoea (OSA). A young person would probably be able to balance such a
      decline in respiratory function using different adaptative mechanisms. Mandibular
      advancement significantly improved respiratory parameters during sleep. The
      possible effect of orthognathic surgery on the upper airways should be
      incorporated into the treatment plan.

PMID- 21074369
TI  - Pituitary volume increase during emerging psychosis.
AB  - BACKGROUND: Morphologic abnormalities of the pituitary gland volume (PV) have
      been reported in schizophrenia, but at what point in time they occur remains
      unclear. This study determines PV across different stages of emerging psychotic
      disorders compared to healthy controls. METHODS: We compared PV of 36 individuals
      with an at-risk mental state (ARMS) for psychosis, 23 patients with a first
      episode psychosis (FEP) and 20 healthy controls (HC). Transition to psychosis was
      monitored using the BPRS transition criteria according to Yung et al. (Yung, A.R.
      et al., 1998. Prediction of psychosis. A step towards indicated prevention of
      schizophrenia. Br. J. Psychiatry Suppl. 172 (33), 14-20). Applying these
      transition criteria, 16 of the 36 ARMS individuals made the transition to
      psychosis (ARMS-T) and 20 did not (ARMS-NT). We traced PV manually on 1mm slices
      of magnetic resonance images in three dimensions (coronal, sagittal and axial)
      blind to group status. We used univariate analysis of covariance (ANCOVA) with PV
      as dependent variable, group and sex as between-subject factors and whole brain
      volume as covariate. RESULTS: PV increased from HC to ARMS-NT to ARMS-T/FEP.
      ANCOVA revealed a significant effect of group (F(3,78)=3.0; p=.036) and a sex *
      group interaction (F(3,78)=6.5; p=.001). Over all groups, women had considerably
      larger PV than men (F(1,78)=9.8; p=.003). CONCLUSIONS: Our findings provide
      further evidence that PV is increased in emerging psychotic disorders, and
      suggest that this is due to a stress-associated activation of the pituitary
      gland.

PMID- 21074370
TI  - Steady-state pharmacokinetics and pharmacodynamics of cefepime administered by
      prolonged infusion in hospitalised patients.
AB  - The objective of this study was to evaluate the steady-state pharmacokinetics and
      pharmacodynamics of cefepime administered by prolonged infusion in hospitalised
      patients requiring antimicrobial therapy. Nine patients received 1g every 8h
      (q8h), infused over 4h, and steady-state pharmacokinetic parameters were
      determined by non-compartmental and compartmental methods. Using these
      pharmacokinetic parameters, 5000-patient Monte Carlo simulations were performed
      to estimate the pharmacokinetic profiles for six prolonged-infusion dosing
      regimens. The probability of target attainment (PTA) was calculated at minimum
      inhibitory concentrations (MICs) ranging from 0.06 MUg/mL to 32 MUg/mL, and the
      cumulative fraction of response (CFR) was calculated for six Gram-negative
      pathogens using MIC data from the Meropenem Yearly Susceptibility Test
      Information Collection (MYSTIC) (2005-2007, USA). The pharmacodynamic target was
      free cefepime concentrations remaining above the MIC for 60% of the dosing
      interval (60% fT>MIC). Mean +/- standard deviation maximum and minimum serum
      concentrations, terminal elimination half-life, elimination rate constant, volume
      of distribution and systemic clearance of cefepime were 32.5 +/- 13.5 MUg/mL, 9.5
      +/- 5.2 MUg/mL, 2.4 +/- 0.7h, 0.316 +/- 0.116 h(-1), 21.3 +/- 6.5L and 6.6 +/-
      3.6L/h, respectively. At the susceptibility breakpoint of 8 MUg/mL, the PTA was
      >90% for 1g and 2g q8h (4-h infusion) and 1g and 2g every 6h (q6h) (3-h
      infusion). For Pseudomonas aeruginosa, the CFR was 88.6% for 1g q8h (4-h
      infusion) and >= 92.7% for 2g q8h (4-h infusion) and 1g and 2g q6h (3-h
      infusion). Cefepime 1g q8h infused over 4h provides excellent target attainment
      for susceptible bacterial pathogens with MICs <=8 MUg/mL.

PMID- 21074371
TI  - Companion animals: a relevant source of extended-spectrum beta-lactamase
      producing fluoroquinolone-resistant Citrobacter freundii.

PMID- 21074372
TI  - Orally administered colistin leads to colistin-resistant intestinal flora and
      fails to prevent faecal colonisation with extended-spectrum beta-lactamase
      producing enterobacteria in hospitalised newborns.
AB  - Colonisation and infection with extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E) is an emerging problem. The aim of this study was to
      investigate whether colistin, which is reported to be effective against
      multiresistant enterobacteria, prevents ESBL-E colonisation in neonates. For
      prophylaxis of necrotising enterocolitis, oral gentamicin (15 mg/kg/day) is
      routinely used in all neonates hospitalised at the Neonatal Intensive Care Unit
      of University Hospital Graz (Austria). During the study period from May 2005 to
      September 2007, three ESBL-E outbreaks (total duration 18 months) occurred.
      During these outbreaks, gentamicin was immediately replaced by oral colistin (8
      mg/kg/day) in all hospitalised neonates. All neonates colonised with ESBL-E
      during the study period were retrospectively analysed with regard to the
      influence of colistin on ESBL-E colonisation. Genetic relatedness of isolates was
      assessed by repetitive sequence-based polymerase chain reaction (rep-PCR). During
      the study period, 30 (4.5%) of 667 neonates were colonised with ESBL-E. Twelve of
      twenty-one patients colonised with Klebsiella pneumoniae (ESBL-Kp) and one of
      nine patients colonised with Klebsiella oxytoca (ESBL-Ko) had received oral
      colistin at time of colonisation with ESBL-E. Amongst ESBL-Kp, the rate of
      colistin resistance was significantly higher in the colistin group (P=0.0075).
      Four different clones of ESBL-Kp and three different clones of ESBL-Ko were
      isolated, indicating the occurrence of patient-to-patient transmission. Colistin
      resistant as well as colistin-susceptible isolates were detected within the same
      clones, indicating induction of resistance. At the dosage used, oral colistin did
      not prevent colonisation with ESBL-E and appeared to select colistin-resistant
      strains or to induce colistin resistance.

PMID- 21074373
TI  - In vitro activity of N-chlorotaurine (NCT) in combination with NH4Cl against
      Trichomonas vaginalis.
AB  - Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is usually treated
      with metronidazole, however resistance is on the rise. In this study, N
      chlorotaurine (NCT), a new endogenous mild active chlorine compound for topical
      use, killed T. vaginalis in vitro within 15 min of treatment at a concentration
      of 55 mM (1%), which is well tolerated by human tissue. The activity of NCT was
      further enhanced by addition of ammonium chloride (NH(4)Cl). A combination of 5.5
      mM (0.1%) NCT plus 19 mM (0.1%) NH(4)Cl killed 100% of trichomonads within 5 min.

PMID- 21074374
TI  - A higher dose of vancomycin in continuous infusion is needed in critically ill
      patients.
AB  - Compared with intermittent infusion, continuous infusion of vancomycin is cheaper
      and logistically more convenient, achieves target concentrations faster, results
      in less variability in serum vancomycin concentrations, requires less therapeutic
      drug monitoring and causes less nephrotoxicity. Given that critically ill
      patients may develop very large volumes of distribution as well as supranormal
      drug clearance, in this study it was shown, despite the limited number of
      patients studied, that to achieve a target plateau concentration of 25mg/L a
      daily dose of 3000 mg of vancomycin in continuous infusion is needed following an
      appropriate loading dose.

PMID- 21074375
TI  - Inappropriate carbapenem use in Singapore public hospitals: opportunities for
      antimicrobial stewardship.

PMID- 21074376
TI  - High levels of multidrug resistance in clinical isolates of Gram-negative
      pathogens from Nigeria.
AB  - In Nigeria, quinolones and beta-lactam antibiotics are widely used to treat
      bacterial infections. This study aimed to identify the prevalence of resistance
      to these drugs and to determine the mechanisms of resistance to these agents. In
      total, 134 non-duplicate, Gram-negative enteric isolates of 13 species from
      different hospitals were investigated for susceptibility to a panel of
      antibiotics, carriage of plasmid-mediated quinolone and beta-lactam resistance
      genes, production of extended-spectrum beta-lactamases (ESBLs), and mutations
      within topoisomerase genes. The level of resistance to all antibiotics tested was
      extremely high, with minimum inhibitory concentrations for 90% of the organisms
      (MIC(90) values) of >= 256 MUg/mL for all drugs. Of the 134 isolates, 92 had
      mutations within the quinolone resistance-determining region (QRDR) of gyrA or
      within gyrA and parC. In addition, the plasmid-mediated quinolone resistance
      genes qnrA, qnrB, aac(6')-Ib-cr and qepA were identified. The qnrD allele, which
      has previously only been found in Salmonella isolates from China, was identified
      in two Proteus isolates and one Pseudomonas isolate. Of the 134 isolates, 23
      (17.2%) carried aac(6')-Ib-cr, 11 (8.2%) carried a qnr variant and 5 (3.7%) were
      positive for qepA. Twenty-eight isolates (20.9%) produced ESBL variants, with a
      CTX-M variant being carried by 25 isolates (18.7%). In addition, six isolates
      (4.5%) carried ampC variants [ACT-1 (1 isolate), DHA-1 (4 isolates) and CMY-2 (1
      isolate)]. This study demonstrates a very high level of multidrug resistance
      amongst Gram-negative enteric bacilli isolated from different sites from patients
      in Nigerian hospitals as well as the presence of a variety of plasmid-associated
      resistance genes, including some identified from Africa for the first time.

PMID- 21074377
TI  - Adverse events associated with intravenous fosfomycin.

PMID- 21074378
TI  - New target concentrations for vancomycin in Hong Kong.

PMID- 21074379
TI  - Effect of pressure on structure of oxide glasses at high pressure: Insights from
      solid-state NMR of quadrupolar nuclides.
AB  - Revealing the structure of oxide glasses at high pressure remains a fundamental
      yet difficult problem in modern physical and chemical sciences. The recent
      advances in solid-state NMR techniques used for quadrupolar nuclides offer a
      considerably improved resolution of atomic sites, unveiling previously unknown
      structural details of oxides glasses at high pressure. Here, we present an
      overview of the recent progress and insights by high-resolution multi-nuclear
      triple quantum magic angle spinning (3QMAS) NMR into pressure-induced changes in
      coordination number, connectivity, and topological disorder in oxide glasses
      quenched from melts at high pressure. (11)B and (27)Al 3QMAS NMR studies of oxide
      glasses show that the formation of highly coordinated Al (([5,6])Al) and four
      coordinated ([4])B are prevalent at high pressure up to 8 GPa. The formation of
      oxygen clusters linking these highly coordinated framework units and Si (e.g.,
      ([5,6])Al-O-([4])Si, ([5,6])Si-O-([4])Si, and Na-O-([5,6])Si) is observed in the
      (17)O NMR spectra at higher pressure, leading to an overall increase in the
      degree of polymerization with pressure. (23)Na MAS NMR spectra of diverse oxide
      glasses at high pressure and high magnetic field also indicate that the Na-O bond
      distance may decrease with pressure. Pressure-induced changes in structurally
      relevant NMR parameters such as the (17)O quadrupolar coupling product (P(q)) for
      the Si-O-Si cluster and (27)Al P(q) for Al sites in oxide glasses indicate the
      occurrence of pressure-induced reductions in the Si-O-Si angle and an increase in
      the Al-O bond length distribution with pressure, indicating an increase in the
      overall topological disorder in oxide glasses with pressure. All the pressure
      induced changes in structure and topology are characterized by strong composition
      dependence. These experimental results highlight a new opportunity to investigate
      the molecular structures of silicate melts at high pressure and reveal
      connections between the microscopic signatures of anomalous and non-linear
      changes in the macroscopic properties of the corresponding liquids. While many
      challenges still remain in the synthesis of oxide glasses with wider range of
      melt composition at higher pressure above 12 GPa, recent progress in enhancement
      of sensitivity and resolution in the solid state NMR hold strong promise for
      study exploring additional details of connectivity among quadrupolar nuclides and
      medium-range order of the more complex, multi-components glasses at high
      pressure.

PMID- 21074380
TI  - Disintegration-controllable stimuli-responsive polyelectrolyte multilayer
      microcapsules via covalent layer-by-layer assembly.
AB  - The disintegration-controllable stimuli-responsive polyelectrolyte multilayer
      microcapsules have been fabricated via the covalent layer-by-layer assembly
      between the amino groups of chitosan (CS) and the aldehyde groups of the oxidized
      sodium alginate (OSA) onto the sacrificial templates (polystyrene sulfonate, PSS)
      which was removed by dialysis subsequently. The covalent crosslinking bonds of
      the multilayer microcapsules were confirmed by FTIR analysis. The TEM analysis
      showed that the diameter of the multilayer microcapsules was <200nm. The diameter
      of the multilayer microcapsules decreased with the increasing of the pH values or
      the ionic strength. The pH and ionic strength dual-responsive multilayer
      microcapsules were stable in acidic and neutral media while they could
      disintegrate only at strong basic media.

PMID- 21074381
TI  - Effect of surface-modified collagen on the adhesion, biocompatibility and
      differentiation of bone marrow stromal cells in poly(lactide-co
      glycolide)/chitosan scaffolds.
AB  - The material-driven differentiation of bone marrow stromal cells (BMSCs) is a
      critical issue in regeneration medicine. In this study, we showed the
      differentiation of BMSCs in 3-D scaffolds consisting of collagen, poly(lactide-co
      glycolide) (PLGA) and chitosan. The results revealed that the collagen-grafted
      PLGA/chitosan scaffolds yielded little cytotoxicity to BMSCs. The scaffold
      containing type I collagen of 640MUg/mL was about 1.2 times the cell adhesion
      efficiency of the corresponding unmodified scaffold. In addition, the
      modification of type I collagen with the density of 640MUg/mL increased about 1.3
      times the cell viability and 1.2 times the biodegradation, respectively. The
      differentiation of BMSCs in PLGA/chitosan scaffolds produced osteoblasts with
      mineral deposition on the substrate. Moreover, the surface collagen promoted the
      formation of mineralized tissue and reduced the amount of phenotypic BMSCs in the
      constructs. However, the induction with neuron growth factor (NGF) inhibited
      osteogenesis and guided the differentiation of BMSCs towards neurons in the
      constructs. Therefore, the combination of collagen-functionalized PLGA/chitosan
      scaffolds, NGF and BMSCs can be promising in neural tissue engineering.

PMID- 21074382
TI  - The magnitude of condensation induced by cholesterol on the mixtures of
      sphingomyelin with phosphatidylcholines-Study on ternary and quaternary systems.
AB  - The studies on the condensing and ordering effect of cholesterol by application
      of the Langmuir monolayer technique are usually performed on binary
      lipid/cholesterol systems. The results concerning a quantitative analysis of
      these effects in multicomponent monolayers are very limited. In this work the
      condensing and ordering effect of cholesterol in ternary (SM/DSPC/Chol and
      SM/DOPC/Chol) and quaternary (SM/DSPC/DOPC/Chol) films was investigated. It was
      evidenced that the systems containing saturated PC (both SM/DSPC and
      SM/DSPC/Chol) are always more condensed and chain-ordered than the systems
      containing unsaturated PC (SM/DOPC and SM/DSPC/DOPC and their mixtures with
      cholesterol). However, the magnitude of condensation provoked by cholesterol at
      higher surface pressures is stronger on the monolayers containing unsaturated PC.
      The addition of cholesterol into SM/PC films induces the increase of chain
      ordering however, the effectiveness of cholesterol as an ordering agent is
      determined by the presence/absence of unsaturated phospholipid. The magnitude of
      the effect of cholesterol on the investigated mixed monolayer was analyzed in the
      context of the influence of sterol on lipid chains (ordering, straightening and
      reorientation of chains) as well as the reorientation of polar heads.

PMID- 21074383
TI  - Electrophoresis of an arbitrarily oriented toroid in an unbounded electrolyte
      solution.
AB  - The electrophoresis of a non-conducting rigid toroid in an unbounded Newtonian
      electrolyte solution having an arbitrary orientation is modeled theoretically
      under the condition of low surface potential. In particular, the influence of the
      orientation angle, defined as the angle between the applied electric field and
      the center line of the toroid, on its electrophoretic behavior as the thickness
      of double layer varies is investigated. The results of numerical simulation
      reveal that both the thickness of double layer and the orientation angle can
      influence appreciably the mobility of the toroid. In general, for a fixed
      orientation, the mobility of the toroid increases with decreasing double layer
      thickness, and for a fixed double layer thickness, the scaled electrophoresis
      mobility increases with increasing orientation angle. If the double layer is
      infinitely thin, then the present result reduces to that predicted by
      Smoluchowski, that is, the scaled electrophoretic mobility of the toroid is
      unity, and is not influenced by its shape. On the other hand, if it is infinitely
      thick, then the present result follows the same trend as that predicted by Henry,
      that is, the electrophoretic mobility of the toroid depends highly on its form
      effect, and the thicker the double layer the smaller that mobility. If the
      thickness of double layer is comparable to the radius of a toroid, the variation
      in the orientation angle can lead to as much as 40% difference in the mobility.

PMID- 21074384
TI  - Heparin-conjugated scaffolds with pore structure of inverted colloidal crystals
      for cartilage regeneration.
AB  - A uniform de novo production of neocartilage is a critical issue in the
      fabrication of tissue-engineered diarthrodial substitutes. The aim of this work
      is to develop homogeneous chondrogenesis in heparinized scaffolds with pores of
      inverted colloidal crystal (ICC) geometry. Monodispersed polystyrene microspheres
      were self-assembled by floating in the medium containing ethylene glycol, dried,
      annealed and infiltrated with heparin/chitin/chitosan gels. The results indicated
      that the colloidal template was in a structure of hexagonal arrays. In addition,
      the regularity of the organized pores in the scaffolds reduced when the
      concentration of ethylene glycol decreased. An increase in the weight percentage
      of heparin enhanced the viability of bovine knee chondrocytes (BKCs) in ICC
      matrices. Over 4 weeks of cultivation, the amount of cartilaginous components
      including BKCs, glycosaminoglycans (GAGs) and collagen enhanced with time.
      Moreover, an increase in the weight percentage of heparin promoted the production
      of BKCs, GAGs and collagen in ICC constructs. Histological and immunochemical
      staining of the cultured ICC constructs revealed minor differences in BKCs, GAGs
      and type II collagen between the peripheral and core regions. Therefore, the
      ordered pores in the heparinized ICC constructs could favor the chondrocyte
      culture to regenerate a uniform distribution of cartilage.

PMID- 21074385
TI  - Carbohydrate decoration of microporous polypropylene membranes for lectin
      affinity adsorption: comparison of mono- and disaccharides.
AB  - Carbohydrates (saccharides) are ubiquitous on the extracellular surface of living
      cells and mediate a myriad of biological recognition and signaling processes.
      Carbohydrate decoration of polymer surfaces with covalent attachment of
      saccharides offers a new realm of opportunities to mimic cellular events such as
      protein recognition and binding. We describe the carbohydrate decoration (surface
      glycosylation) of poly(2-hydroxyethyl methacrylate)-grafted microporous
      polypropylene membranes (poly(HEMA)-g-MPPMs) with mono- and disaccharides.
      Galactose, lactose, glucose, and maltose were covalently attached on the surfaces
      of poly(HEMA)-g-MPPMs and were compared in detail. The process was verified by
      solid state (13)C NMR spectra. Membranes with high binding degree (BD) of
      saccharide ligands on the surfaces were facilely prepared from poly(HEMA)-g-MPPMs
      with high grafting degree (GD) of poly(HEMA). For poly(HEMA)-g-MPPM with the same
      GD of poly(HEMA), the BD of disaccharides is lower than that of monosaccharides
      and the disaccharide-decorated MPPMs are more hydrophilic than the monosaccharide
      decorated ones. The carbohydrate-decorated MPPMs prepared from galactose,
      lactose, glucose, and maltose (denoted as MPPM-Gal, MPPM-Lac, MPPM-Glc and MPPM
      Mal, respectively) recognize and adsorb specifically one of the two lectins,
      concanavalin A (Con A) and peanut agglutinin (PNA). As the BD of saccharide
      increases, the "glycoside cluster effect" plays a primary role in lectin
      adsorption. MPPM-Lac has enhanced affinity to PNA as compared with MPPM-Gal
      having similar BD of saccharide., on the other hand, MPPM-Mal shows no enhanced
      affinity to Con A in comparison with MPPM-Glc as the BD of saccharide is above
      0.9 MUmol/cm(2), where the "glycoside cluster effect" occurs.

PMID- 21074386
TI  - [Circular shunting of blood: a complication of neonatal Ebstein anomaly].
AB  - We report a severe neonatal presentation of Ebstein anomaly with homodynamic
      aggravation at birth attributed to patent ductus arteriosus and circular shunt.
      Prenatal diagnosis of Ebstein anomaly of the tricuspid valve with functional
      pulmonary atresia was made at 37 weeks gestation by fetal two- and three
      dimensional echocardiography. A cesarean section was performed in view of poor
      fetal tolerance. The newborn was born with hydrops and multivisceral failure. A
      post-natal echocardiography demonstrated a left-to-right shunt across the patent
      ductus arteriosus and functional pulmonary atresia with severe pulmonary
      insufficiency with absent forward flow. This created a circular shunt, where
      blood flowed through the ductus to the pulmonary arteries, retrograde through the
      pulmonary artery and Ebstein valve, across the patent foramen ovale and out the
      aorta. Prostaglandin E1 infusion was stopped, resulting in clinical and
      echocardiographic improvement. The management of the phenomenon of a circular
      shunt across a patent ductus arteriosus with Ebstein malformation involves
      promoting early ductal closure by stopping prostaglandin therapy.

PMID- 21074387
TI  - [From teratology to mythology: ancient legends].
AB  - The mythology of the Greeks and Romans is full of monsters of fiction: giants,
      cyclops, centaurs, hydras, Gorgons... The accounts of travelers, reproduced in
      the Natural History of Pline l'Ancien reported the existence, in distant
      countries, of men with a dog's head (baboons), of men with a single tall foot
      (sciapode), beings whose face is embedded in the chest (or acephala blemmyes), to
      which must be added a wide variety of men with no mouth, no nose, or equipped
      with giant ears or feet turned backwards, as well as hermaphrodites. Teratology
      reports on monstrous births, which have constituted the factual basis from which
      the imagination conceived adults whose morphology corresponds to the monsters of
      legend. Newborns sirenomelia were behind the legend of sciapode and sirens.
      Cyclopia have inspired the legend of the cyclops. Anencephaly probably explains
      the description of headless or blemmyes. The genesis of the legend of baboons may
      have multiple origins: firstly the existence of people suffering from congenital
      hypertrichosis, on the other hand, the influence of Egyptian mythology where the
      god Anubis has a dog's head. The acardiac fetus may explain some monstrous forms,
      features the work of Hieronymus Bosch. The significance of the monsters of
      legend, their genesis, their persistence through the ages is complex. By
      approaching teratology, we added a new field of exploration of real monsters of
      antiquity and Middle Ages.

PMID- 21074389
TI  - [An unusual case of hydronephrosis in a child].

PMID- 21074388
TI  - [The host community of a child with food allergies: the personalized care project
      (PCP)].
AB  - The personalized care project (PCP) can manage allergic emergencies that may
      occur during school hours. Other objectives are to facilitate academic
      achievement, social and professional integration of children and adolescents with
      chronic illness such as food allergy, by promoting education through certain
      changes. The PCP is derived from official files including Circular N(o) 2003-135
      of September 8 and the inter-ministerial circular of 25 June 2001. The family
      must request a protocol with the host school principal or school head. Then, the
      doctor of Education organizes the drafting of the document based on information
      provided by the physician (or allergist).

PMID- 21074390
TI  - [Dyslexia: clinical characteristics].
AB  - Dyslexia is characterized by a severe, persistent reading disorder occurring in
      an intelligent child. In the large field of learning disabilities, dyslexia is
      related to a cerebral dysfunction well described with Imagery and genetic
      studies. Nevertheless the diagnosis of dyslexia cannot be done by another way
      than clinical symptoms. Optimizing the management of children with dyslexia is a
      critical issue and is now possible, thanks to the improvement of neurosciences
      data and the mobilization of the key stakeholders. The knowledge of the precise
      symptoms is essential in order to lead the child's doctor able to improve
      coordination and harmonization of teaching and care and guidance of parents.

PMID- 21074391
TI  - Diversity, distribution and biogeography of testate amoebae in China:
      implications for ecological studies in Asia.
AB  - Testate amoebae are a group of shelled protozoa that occur in high density
      populations in wet environments. More than 1900 testate amoebae species or
      subspecies have been reported in published literature over the last 200 years,
      from many regions of the world. Testate amoebae are classified as Lobosea or
      Filosea respectively, according to the presence of lobose or filiform
      pseudopodia. Testate amoebae have proved an interesting group of indicator
      organisms in palaeoenvironmental studies and have also been used as bioindicators
      of human impact on ecosystems. Until recently, the testate amoebae of China were
      unknown to most western scientists, but our knowledge has improved greatly over
      the past 20 years. This paper summarizes the testate amoebae research in China
      along with relevant data from other countries in Asia, and provides the necessary
      context for future research.

PMID- 21074392
TI  - Involvement of oxidative stress in taxol-induced apoptosis in chronic myelogenous
      leukemia K562 cells.
AB  - It is now well accepted that taxol exhibits cytotoxicity and antitumor activity
      in many human tumors through microtubule stabilization and induction of G2/M cell
      cycle arrest with final extensive cell apoptosis. Since many anti-cancer agents
      exert their cytotoxic effects through reactive oxygen species (ROS), we were
      interested to evaluate whether oxidative stress is involved in taxol-induced
      cytotoxicity among human leukemia K562 cells. Our results showed that induction
      of apoptosis was associated with generation of ROS and glutathione (GSH)
      depletion. The increase in ROS production and apoptosis were both suppressed by
      antioxidant N-acetyl-l-cysteine (NAC). Moreover, taxol caused an increase in c
      Jun NH(2)-terminal kinase (JNK) and p38 activities, two of the well known
      mediators of the stress activation pathways. Attenuation of JNK expression in the
      presence of NAC might indicate the modulation of the level of JNK activity by
      ROS. Furthermore, our data indicated that Bcl-2alpha was down-regulated in taxol
      treated cells and its expression was modulated by ROS and JNK activity. The
      activities of caspase-9 and -3 were also increased upon treatment with taxol;
      however, pre-treatment of cells with NAC or JNK inhibitor (SP600125) impeded
      taxol-mediated caspase activation and apoptosis in K562 cells, suggesting that
      JNK acts upstream of the caspases. Taken together, these results indicate that
      taxol induces apoptosis in chronic myelogenous leukemia cells by inducing
      intracellular oxidative stress and JNK activation pathway.

PMID- 21074393
TI  - Ultrastructural studies of epidermis keratinization in grass snake embryos Natrix
      natrix L. (Lepidosauria, Serpentes) during late embryogenesis.
AB  - The changes and biochemical features of the epidermis that accompany the
      differentiation and embryonic shedding complex formation in grass snake Natrix
      natrix L. embryos were studied ultrastructurally and immunocytochemically with
      two panels of antibodies (AE1, AE3, AE1/AE3; anti-cytokeratin, pan mixture, Lu-5
      and PCK-26). All observed changes in the ultrastructure of the cells forming the
      epidermal layers were associated with the physiological changes that occurred in
      the embryonic epidermis, such as changing of the manner of nutrition and
      keratinization leading to the embryonic shedding complex formation. The layers
      that originated first (basal, outer and inner periderm and clear layer)
      differentiated very early and rapidly. Rapid differentiation was also observed in
      the layers that are very important for the functioning of the epidermis in Natrix
      embryos (oberhautchen and beta-layers). They started to differentiate at
      developmental stage IX, and then fused and formed the embryonic shedding complex
      at developmental stage XI. During the embryonic development of the grass snake
      the smallest changes appeared in the ultrastructure of the cells in the mesos and
      alpha-layers because they perform supplementary functions in the process of
      embryonic molting. They were undifferentiated until the end of embryonic
      development and started to differentiate just before the first adult molting.
      AE1/AE3, anti-cytokeratin, pan mixture, Lu-5 and PCK-26 antibodies immunolabeled
      clear layer, oberhautchen and beta-layers at the latest phase of developmental
      stage XI. It should be noted that these antibodies did not immunolabel the alpha
      layer until hatching. The presence of alpha-keratin immunolabeling in layers that
      were keratinized, particularly in the oberhautchen and beta-layers in embryos,
      indicated that they were not as hard as in fully mature individuals.

PMID- 21074394
TI  - Quantitative CT measures of emphysema and airway wall thickness are related to
      D(L)CO.
AB  - There is limited knowledge on the relationship between diffusing capacity of the
      lung for carbon monoxide (D(L)CO) and quantitative computed tomography (CT)
      measures of emphysema and airway wall thickness. STUDY QUESTION: What is the
      relationship between D(L)CO and the quantitative CT measures of emphysema and
      airway wall thickness in subjects with and without COPD? METHODS: We included 288
      COPD subjects (70% men) and 425 non-COPD subjects (54% men). All subjects were
      current or ex-smokers older than 40 years and all subjects underwent spirometry,
      diffusing capacity tests and CT examination. Quantitative CT measures included %
      low attenuation areas < -950 HU (%LAA) and standardized airway wall thickness
      (AWT-Pi10). RESULTS: Multiple linear regression analyses showed significant
      associations between D(L)CO and both %LAA and AWT-Pi10 in the COPD group. The
      adjusted regression coefficients (SE) for D(L)CO (mmol min(-1) kPa(-1)) were 
      1.15 (0.11) per 10% increase in %LAA and 0.08 (0.03) per 0.1 mm increase in AWT
      Pi10, and the models' adjusted R(2) was 0.65 and 0.49, respectively. CONCLUSIONS:
      CT measured emphysema explains a large fraction of the variation of D(L)CO among
      COPD subjects, and more so in men. Airway wall thickness is also significantly
      associated with D(L)CO, but explains a much smaller fraction of the variation.

PMID- 21074395
TI  - Trace elements in compost regulation: the case of Spain.
AB  - We use the example of the Spanish Decree on Fertilizers (2005) to discuss the
      need of new horizontal regulations for assessing the quality of all the materials
      reaching the soil as amendments of fertilizers, in particular in what concerns
      potentially toxic trace elements in compost. Here it is proposed that the new
      regulations take into account the following: establishing maximum legal limits
      for the total loads for each element when compost is added to agricultural soils;
      establishing the maximum total concentration and bioavailability of each element
      in the final compost; and that they take into account the soil characteristics
      for establishing those limits.

PMID- 21074396
TI  - Fabrication of stable antibody-modified field effect transistors using electrical
      activation of Schiff base cross-linkages for tumor marker detection.
AB  - In this paper, we present a method of fabricating a rigid antibody-immobilized
      surface using electric activation of a glutaraldehyde (GA)-modified
      aminopropylsilyl surface for stable antibody-modified field effect transistors
      (FETs). Electric activation of the GA-modified gate surface of the FET reduces
      Schiff bases, which are easily hydrolyzed and collapsed, formed between GA and 3
      aminopropyltriethoxysilane, resulting in preventing the immobilized antibodies
      from desorbing from the surface. The lack of Raman peaks that could be assigned
      to a Schiff base after the electrical activation of the GA-modified surface
      indicated that the electric activation had reduced the Schiff base. The use of
      the antibody-modified FETs has three advantages for the detection of antigens:
      increased sensitivity, distinct recognition ability, and improved
      reproducibility. A tumor marker, alpha-fetoprotein (AFP), was quantitatively
      detected up to a concentration of 10 ng/mL using the antibody-modified FET. The
      detection ability of the FET accomplished a cutoff value of hepatic cancer. The
      quantitative detection of AFP in a solution with contaminating proteins was also
      demonstrated. This electric activation method is applicable to other antibody
      modified FETs.

PMID- 21074397
TI  - Silicon-based microfabricated microbial fuel cell toxicity sensor.
AB  - Microbial fuel cells (MFCs) have been used for several years as biosensors for
      measuring environmental parameters such as biochemical oxygen demand and water
      toxicity. The present study is focused on the detection of toxic matter using a
      novel silicon-based MFC. Like other existing toxicity sensors based on MFCs, this
      device is capable of detecting the variation on the current produced by the cell
      when toxic compounds are present in the medium. The MFC approach presented in
      this work aims to obtain a simple, compact and planar device for its further
      application as a biosensor in the design and fabrication of equipment for
      toxicity monitoring. It consists on a proton exchange membrane placed between two
      microfabricated silicon plates that act as current collectors. An array of square
      80 MUm * 80 MUm vertical channels, 300 MUm deep, have been defined trough the
      plates over an area of 6 mm * 6 mm. The final testing assembly incorporates two
      perspex pieces positioned onto the plates as reservoirs with a working volume of
      144 MUL per compartment. The operation of the microdevice as a direct electron
      transfer MFC has been validated by comparing its performance against a larger
      scale MFC, run under the same conditions. The device has been tested as a
      toxicity sensor by setting it at a fixed current while monitoring changes in the
      output power. A drop in the power production is observed when a toxic compound is
      added to the anode compartment. The compact design of the device makes it
      suitable for its incorporation into measurement equipment either as an individual
      device or as an array of sensors for high throughput processing.

PMID- 21074398
TI  - Nickel oxide microfibers immobilized onto electrode by electrospinning and
      calcination for nonenzymatic glucose sensor and effect of calcination temperature
      on the performance.
AB  - Nickel oxide microfibers (NiO-MFs) were directly immobilized onto the surface of
      fluorine tin oxide (FTO) electrode by electrospinning and calcination without
      using any immobilization matrix for nonenzymatic glucose sensor. Morphology and
      structure of NiO-MFs were characterized by scanning electron microscopy (SEM),
      energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction pattern (XRD).
      The electrochemical and electrocatalytic performances of the NiO-MFs modified
      electrodes prepared at different calcination temperatures ranging from 300 to 500
      degrees C were evaluated by cyclic voltammetry (CV). The CV results have
      demonstrated that NiO-MFs modified electrode prepared at 300 degrees C displayed
      distinct increase in electrocatalytic activity toward the oxidation of glucose,
      which is explored to develop an amperometric nonenzymatic glucose sensor. The NiO
      MFs prepared at 300 degrees C based amperometric nonenzymatic glucose sensor has
      ultrasensitive current (1785.41 MUA mM(-1) cm(-2)) response and low detection
      limit of 3.3*10(-8) M (signal/noise ratio (S/N)=3), which are among the best
      values reported in literature. Additionally, excellent selectivity and stability
      have also been obtained.

PMID- 21074399
TI  - Signal enhancement in DNA microarray using dye doped silica nanoparticles:
      application to human papilloma virus (HPV) detection.
AB  - DNA microarray is a powerful tool for the parallel of nucleic acids and other
      biologically significant molecules. In this communication we report an easy and
      cheap synthesis route for incorporating organic dyes into monodisperse inorganic
      silica nanoparticles and their application on the detection of carcinogenic risky
      Human Papilloma Virus using DNA microarray technology. We correlate our system
      with conventional direct dyes and commercial quantum dots, with a promising
      increase in optical signal, and a related decrease of the limit of detection,
      thus giving a remarkable improvement in this technique towards early diagnosis of
      diseases and trace level detection of dangerous biological contaminants.

PMID- 21074400
TI  - WITHDRAWN: Classification and prediction of Chinese rice wines with different
      marked ages by using a voltammetric electronic tongue.
AB  - This article has been withdrawn at the request of the author and editor. The
      Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21074401
TI  - Comprehensive identification and quantification of microbial transcriptomes by
      genome-wide unbiased methods.
AB  - Genomic tiling array transcriptomics and RNA-seq are two powerful and rapidly
      developing approaches for unbiased transcriptome analysis. Providing
      comprehensive identification and quantification of transcripts with an
      unprecedented resolution, they are leading to major breakthroughs in systems
      biology. Here we review each step of the analysis from library preparation to the
      interpretation of the data, with particular attention paid to the possible
      sources of artifacts. Methodological requirements and statistical frameworks are
      often similar in both the approaches despite differences in the nature of the
      data. Tiling array analysis does not require rRNA depletion and benefits from a
      more mature computational workflow, whereas RNA-Seq has a clear lead in terms of
      background noise and dynamic range with a considerable potential for evolution
      with the improvements of sequencing technologies. Being independent of prior
      sequence knowledge, RNA-seq will boost metatranscriptomics and evolutionary
      transcriptomics applications.

PMID- 21074402
TI  - Evaluation of patient residual deviation and its impact on dose distribution for
      proton radiotherapy.
AB  - The residual deviations after final patient repositioning based on bony anatomy
      and the impact of such deviations on the proton dose distributions was
      investigated. Digitally reconstructed radiographs (DRRs) and kilovoltage (kV)
      "portal verification" images from 10 patients treated with passively scattered
      proton radiotherapy was used to estimate the residual deviation. These changes
      were then applied to the location of isocenter points that, in effect, moved the
      isocenter relative to the apertures and compensators. A composite verification
      plan was obtained and compared with the original clinical treatment plan to
      evaluate any changes in dose distributions. The residual deviations were fitted
      to a Gaussian distribution with MU = -0.9 +/- 0.1 mm and sigma = 2.55 +/- 0.07
      mm. The dose distribution showed under- and overcovered dose spots with complex
      dose distributions both in the target volumes and in the organs at risk. In some
      cases, this amounts to 63.5% above the intended clinical plan. Although patient
      positioning is carefully verified before treatment delivery and setup
      uncertainties are accounted for by using compensator smearing and aperture
      margins, a residual shift in a patient's position can considerably affect the
      dose distribution.

PMID- 21074403
TI  - Accidental local anesthetic overdose due to epidural pump malfunction.

PMID- 21074404
TI  - Exacerbation of acetazolamide-responsive sodium channel myotonia by uterotonic
      agents.
AB  - The symptoms of myotonia can worsen during pregnancy and tocolysis with ritodrine
      has been associated with rhabdomyolysis. We describe a patient with myotonia who
      developed hypertonus immediately following the administration of uterotonic
      agents. A 24-year-old, G2P1 at 31 weeks of gestation with a history of
      acetazolamide-responsive myotonia presented with premature rupture of membranes.
      During cesarean delivery she experienced significant hypertonus of the upper
      limbs, shoulders, fingers, and mouth immediately after intravenous administration
      of oxytocin 5 IU and methylergometrine maleate 0.2mg. The mechanism underlying
      increased muscle tone in response to these drugs remains unclear.
      Anesthesiologists should be especially attentive to the administration of
      uterotonic drugs during the management of pregnant myotonia patients.

PMID- 21074405
TI  - Attenuation of the hypertensive response to tracheal intubation in patients with
      severe preeclampsia: a UK postal survey.

PMID- 21074406
TI  - Skin disinfection before spinal anaesthesia for caesarean section: a survey of UK
      practice.

PMID- 21074407
TI  - Pseudokinases-remnants of evolution or key allosteric regulators?
AB  - Protein kinases provide a platform for the integration of signal transduction
      networks. A key feature of transmitting these cellular signals is the ability of
      protein kinases to activate one another by phosphorylation. A number of kinases
      are predicted by sequence homology to be incapable of phosphoryl group transfer
      due to degradation of their catalytic motifs. These are termed pseudokinases and
      because of the assumed lack of phosphoryltransfer activity their biological role
      in cellular transduction has been mysterious. Recent structure-function studies
      have uncovered the molecular determinants for protein kinase inactivity and have
      shed light to the biological functions and evolution of this enigmatic subset of
      the human kinome. Pseudokinases act as signal transducers by bringing together
      components of signalling networks, as well as allosteric activators of active
      protein kinases.

PMID- 21074408
TI  - Lifestyle factors associated concurrently and prospectively with co-morbid
      cardiovascular disease in a population-based cohort of colorectal cancer
      survivors.
AB  - AIMS: To assess self-reported lifetime prevalence of cardiovascular disease (CVD)
      among colorectal cancer survivors, and examine the cross-sectional and
      prospective associations of lifestyle factors with co-morbid CVD. METHODS:
      Colorectal cancer survivors were recruited (n=1966). Data were collected at
      approximately 5, 12, 24 and 36 months post-diagnosis. Cross-sectional findings
      included six CVD categories (hypercholesterolaemia, hypertension, diabetes, heart
      failure, kidney disease and ischaemic heart disease (IHD)) at 5 months post
      diagnosis. Longitudinal outcomes included the probability of developing (de novo)
      co-morbid CVD by 36 months post-diagnosis. Lifestyle factors included body mass
      index, physical activity, television (TV) viewing, alcohol consumption and
      smoking. RESULTS: Co-morbid CVD prevalence at 5 months post-diagnosis was 59%,
      and 16% of participants with no known CVD at the baseline reported de novo CVD by
      36 months. Obesity at the baseline predicted de novo hypertension (odds ratio
      [OR]=2.20, 95% confidence intervals [CI]=1.09, 4.45) and de novo diabetes
      (OR=6.55, 95% CI=2.19, 19.53). Participants watching >4h of TV/d at the baseline
      (compared with <2h/d) were more likely to develop ischaemic heart disease by 36
      months (OR=5.51, 95% CI=1.86, 16.34). CONCLUSION: Overweight colorectal cancer
      survivors were more likely to suffer from co-morbid CVD. Interventions focusing
      on weight management and other modifiable lifestyle factors may reduce functional
      decline and improve survival.

PMID- 21074409
TI  - A model of vascular tumour growth in mice combining longitudinal tumour size data
      with histological biomarkers.
AB  - Optimising the delivery of antiangiogenic drugs requires the development of drug
      disease models of vascular tumour growth that incorporate histological data
      indicative of cytostatic action. In this study, we formulated a model to analyse
      the dynamics of tumour progression in nude mice xenografted with HT29 or HCT116
      colorectal cancer cells. In 30 mice, tumour size was periodically measured, and
      percentages of hypoxic and necrotic tissue were assessed using
      immunohistochemistry techniques on tumour samples after euthanasia. The
      simultaneous analysis of histological data together with longitudinal tumour size
      data prompted the development of a semi-mechanistic model integrating random
      effects of parameters. In this model, the peripheral non-hypoxic tissue
      proliferates according to a generalised-logistic equation where the maximal
      tumour size is represented by a variable called 'carrying capacity'. The ratio of
      the whole tumour size to the carrying capacity was used to define the hypoxic
      stress. As this stress increases, non-hypoxic tissue turns hypoxic. Hypoxic
      tissue does not stop proliferating, but hypoxia constitutes a transient stage
      before the tissue becomes necrotic. As the tumour grows, the carrying capacity
      increases owing to the process of angiogenesis. The model is shown to correctly
      predict tumour growth dynamics as well as percentages of necrotic and hypoxic
      tissues within the tumour. We show how the model can be used as a theoretical
      tool to investigate the effects of antiangiogenic treatments on tumour growth.
      This model provides a tool to analyse tumour size data in combination with
      histological biomarkers such as the percentages of hypoxic and necrotic tissue
      and is shown to be useful for gaining insight into the effects of antiangiogenic
      drugs on tumour growth and composition.

PMID- 21074410
TI  - S100A14 regulates the invasive potential of oral squamous cell carcinoma derived
      cell-lines in vitro by modulating expression of matrix metalloproteinases, MMP1
      and MMP9.
AB  - Despite the differential expression of S100A14 (a newly identified S100 member)
      in various human cancers including oral squamous cell carcinomas (OSCCs), its
      biological role in tumour invasion has not been characterised. The aim of this
      study was thus to investigate the possible role of S100A14 in OSCC cell invasion.
      Using immunohistochemistry in normal (n=13), dysplastic (n=10) and OSCC (n=16)
      archival tissues, S100A14 protein was found to be down-regulated/lost with
      concomitant membrane to cytoplasmic translocation in OSCCs, especially in the
      invading tumour islands. These expression data were corroborated by profiling
      S100A14 mRNA expression using quantitative RT-PCR (qRT-PCR) in an in vitro human
      OSCC progression model consisting of cell-lines derived from normal (n=3),
      dysplastic (n=3) and OSCC (n=8) tissues. Employing in vitro Matrigel invasion
      assay, we demonstrated that retroviral vector mediated over-expression of S100A14
      resulted in significant decrease in the invasive potential of OSCC derived CaLH3
      and H357 cell-lines whereas siRNA mediated knockdown resulted in significant
      increase in the invasive potential of CaLH3 cell-line. Pathway focused PCR array
      and validation using qRT-PCR revealed that S100A14 over-expression was associated
      with down-regulation of MMP1 and MMP9 mRNAs in both CaLH3 and H357 cell-lines.
      Further, S100A14 over-expression was found to be associated with suppression of
      MMP9 gelatinolytic activity in CaLH3 cell-line. Additionally, an inverse
      correlation between mRNA expression levels of MMP1 and MMP9 with S100A14 was
      found in 19 cases of OSCCs. Collectively, these data provide the first evidence
      for a role of S100A14 protein in regulation of OSCC cell invasion by modulating
      expression of MMP1 and MMP9.

PMID- 21074411
TI  - Pilot study of F(18)-Fluorodeoxyglucose Positron Emission Tomography/computerised
      tomography in Wilms' tumour: correlation with conventional imaging, pathology and
      immunohistochemistry.
AB  - Wilms' tumour is the second most common paediatric solid tumour. Prognosis is
      good although higher stage disease carries significant mortality and treatment
      related morbidity. In the UK, risk stratification is based on histological
      response to pre-operative chemotherapy. F(18)-Fluorodeoxyglucose Positron
      Emission Tomography (F(18)FDG-PET) is an emerging functional imaging technique in
      paediatric oncology. Little is known about the relationship between F(18)FDG-PET
      images and the disease process of Wilms' tumour. We performed F(18)FDG-PET/CT
      scans in seven children with Wilms' tumour after induction chemotherapy,
      immediately before surgery. The standard uptake values (SUV) of F(18)FDG-PET/CT
      images were related to conventional imaging and histopathological findings. In
      total seven children were studied. F(18)FDG-PET/CT was consistently safely
      performed. All tumours showed F(18)FDG activity. Four tumours had activity with
      SUV/bw max >5 g/ml. Histological examination of these active areas revealed
      viable anaplastic Wilms' tumour. Furthermore, in these four tumours GLUT-1 and
      Ki67 immunostaining was strongly positive. Three further tumours demonstrated
      lower uptake (SUV/bw max <5 g/ml), which represented areas of microscopic foci of
      residual viable tumour mixed with post chemotherapy change. Metastatic disease
      was F(18)FDG avid in two of four children with stage four diseases. In
      conclusion, following chemotherapy, active Wilms' tumour is F(18)FDG avid and
      higher SUV was seen in histologically high risk disease.

PMID- 21074412
TI  - MAPK and PI3K signalling differentially regulate angiogenic and lymphangiogenic
      cytokine secretion in squamous cell carcinoma of the head and neck.
AB  - Vascular endothelial growth factors (VEGF-C and VEGF-A) play important roles in
      tumour-induced lymphangiogenesis and angiogenesis, respectively, key processes
      implicated in promoting tumour growth and metastatic spread. Previous work from
      our laboratory has shown that EGFR overexpression in squamous carcinomas of the
      head and neck (SCCHN) is linked to high levels of VEGF-A and VEGF-C (but low
      levels of VEGF-D) and is associated with poor prognosis. The present study
      explored the signalling pathways regulating the induction of VEGF-C and VEGF-A in
      the SCCHN cell lines CAL 27 and Detroit 562. The addition of exogenous EGF
      induced the expression of VEGF-C and VEGF-A in a concentration-dependent manner
      and this was blocked by a selective EGFR inhibitor, gefitinib. In both cell lines
      stimulated with endogenous or exogenous ligand, inhibition of MEK1/2 (with U0126
      or PD98059) or PI3K (with PI-103 or LY294002) resulted in a marked reduction of
      EGFR-induced VEGF-A expression, whereas exogenous EGF-induced VEGF-C upregulation
      was blocked by inhibitors of MEK but not PI3K. Inhibition of p38 MAPK suppressed
      EGF-induced VEGF-C upregulation in CAL 27 cells, but inhibited EGF-induced VEGF-A
      upregulation in Detroit 562. Taken together, our evidence suggests that both
      endogenous and exogenous EGFR activation induces VEGF-A expression requiring both
      PI3K and MAPK signalling whereas VEGF-C expression is dependent on MAPK, but not
      the PI3K or mTOR pathways in SCCHN cell lines. p38 MAPK appears to be
      differentially linked to either VEGF-A or VEGF-C regulation in different cellular
      contexts.

PMID- 21074413
TI  - Anaphylactic response to blue dye during sentinel lymph node biopsy.
AB  - The sentinel lymph node (SLN) procedure is now used routinely for the staging of
      clinically node-negative patients with early breast cancer. Two identification
      techniques exist: colorimetric and isotopic. These can be used alone or in
      combination. The combined method is associated with an increased identification
      rate. However, allergic and adverse reactions to blue dyes have been reported.
      The objective of this review was to determine the incidence of such events and to
      discuss alternative approaches. The authors conducted a search of the MEDLINE and
      EMBASE databases for reports of anaphylactic responses to isosulfan blue dye and
      patent blue V dye. Allergic reaction to the dyes isosulfan blue and patent blue V
      is rare and the reported incidence varies between 0.07% and 2.7%. Methylene blue
      dye appears to be safer, with no cases of allergic events having been reported.
      However, allergy tests in some patients have proven that there is cross
      reactivity between isosulfan blue dye and methylene blue dye. Even though the
      risk of an anaphylactic response is low, this raises questions about the
      usefulness of colorimetric detection of SLN and whether alternatives to the use
      of the isosulfan and patent blue V dyes, such as methylene blue, exist.

PMID- 21074414
TI  - Anammox treatment of high-salinity wastewater at ambient temperature.
AB  - The present study aims to provide a realistic understanding of how the anammox
      bacterial community and nitrogen removal performance are affected by increasing
      salt concentrations at ambient temperature. A laboratory-scale investigation was
      conducted for 92 days, during which the reactor was fed with synthetic inorganic
      wastewater composed mainly of NH(4)(+)-N and NO(2)(-)-N. A stable nitrogen
      removal rate of 4.5+/-0.1 kg Nm(-3) day(-1) was obtained at a NaCl concentration
      of 30 g/L, suggesting that the enriched anammox consortium adapted to high salt
      concentrations. This NRR level is the highest level ever reported at high salt
      concentration. The addition of salt in the influent was expected to improve the
      physical properties of the biomass. The anammox bacterium KU2, which was
      confirmed to adapt to high salt concentrations, was considered to be responsible
      for the stable nitrogen removal performance. The successful application of
      anammox technology in this study provides an alternative for the treatment of
      wastewater containing high concentrations of salt and nitrogen.

PMID- 21074415
TI  - Synthesis and characterization of a novel super-absorbent based on wheat straw.
AB  - In order to develop an eco-friendly polymer, a novel super-absorbent polymer was
      prepared by graft copolymerization of acrylic acid (AA), acrylic amide (AM) and
      dimethyl diallyl ammonium chloride (DMDAAC) onto the pretreatment wheat straw
      (PTWS). The molecular structure of the super-absorbent was confirmed by FTIR. The
      factors that can influence absorbencies of the super-absorbent resin (SAR) were
      investigated, such as weight ratio between the monomers, the ratio of PTWS to
      monomers, the amount of initiator and cross-linker, temperature reaction time and
      neutralization degree of AA. The SAR has the water absorbency of 133.76 g/g in
      distilled water and 33.83 g/g in 0.9 wt.% NaCl solution.

PMID- 21074416
TI  - Extractive biofilm membrane bioreactor with energy recovery from excess aeration
      and new membrane fouling control.
AB  - Hybrid biofilm membrane bioreactor (BF-MBR) system featuring new mechanisms for
      recovering the excess energy from air bubbling flow in the biofilm reactor and
      for controlling membrane biofouling was preliminarily investigated in this study.
      Alternative design of the biofilm reactor was developed to utilize the bubbling
      flow from the lower aerobic chamber to generate a mechanical mixing in the upper
      anoxic chamber in the vertical biofilm reactor. Suspended solid (SS)
      concentration in the system was hydrodynamically controlled to be lower than 70
      mg/L. The ultraviolet (UV) inactivation unit was integrated with the membrane
      filtration tank to limit biological activities for biofoulant productions and to
      decelerate the unwanted biofilm formation in the permeate tube. Membrane
      relaxations at various operating conditions were studied for optimum membrane
      fouling reductions under low SS environment. Combinations of membrane relaxation
      and the UV inactivation significantly prolonged sustainable operation periods of
      the membrane filtration in the BF-MBR process.

PMID- 21074417
TI  - Analysis of light regime in continuous light distributions in photobioreactors.
AB  - Maximum photobioreactor (PBR) efficiency is a must in applications such as the
      obtention of microalgae-derived fuels. Improving PBR performance requires a
      better understanding of the "light regime", the varying irradiance that
      microalgal cells moving in a dense culture are exposed to. We propose a
      definition of light regime that can be used consistently to describe the
      continuously varying light patterns in PBRs as well as in light/dark cycles.
      Equivalent continuous and light/dark regimes have been experimentally compared
      and the results show that continuous variations are not well represented by
      light/dark cycles, as had been widely accepted. It has been shown that a correct
      light regime allows obtaining photosynthetic rates higher than the corresponding
      to continuous light, the so-called "flashing light effect" and that this is
      possible in commercial PBRs. A correct PBR operation could result in
      photosynthetic efficiency close to the optimum eight quanta per O(2).

PMID- 21074418
TI  - Enhancing aspergiolide A production from a shear-sensitive and easy-foaming
      marine-derived filamentous fungus Aspergillus glaucus by oxygen carrier addition
      and impeller combination in a bioreactor.
AB  - Production enhancement of a novel antitumor compound aspergiolide A from shear
      sensitive and easy-foaming marine-derived fungus Aspergillus glaucus HB1-19 in a
      5-l stirred bioreactor was investigated. Two types of impellers, i.e., six-flat
      blade disc turbine impeller (DT) and three-sector-blade pitched blade turbine
      impeller (PB) were used in this work. In cultures with fermentation medium, the
      combination of upper PB and lower DT led to the maximum dry biomass (13.8 g/l)
      and aspergiolide A production (19.3 mg/l). However, two PBs brought the highest
      aspergiolide A yield coefficient (1.9 mg/g dry biomass) despite it produced the
      lowest dry biomass (5.3 g/l). By contrast, two DTs and the upper DT and lower PB
      showed insignificant results. Feeding 0.35% (v/v) n-dodecane in cultures with
      upper PB and lower DT further improved aspergiolide A production by 31.0%, i.e.,
      25.3 mg/l, which is also 322% higher than that in the ordinary cultures with two
      DTs.

PMID- 21074419
TI  - Biomass Cost Index: mapping biomass-to-biohydrogen feedstock costs by a new
      approach.
AB  - Making decisions and developing policy in the field of biofuel and bioenergy is
      complex because of the large number and potential arrangements of feedstocks,
      technologies and supply chain options. Although, the technical optimisation and
      sustainability of any biomass to biofuel production chain is of major importance,
      the overall chain cost is still considered as the key for their market
      deployment. A significant percentage of this cost is attributed to primary
      generation, transportation/handling and pretreatment of the biomass. The
      separation of the system into smaller semi-independent sub-systems and dealing
      with their interfaces, provides the pathway to map this complex landscape. The
      main scope of this work is to present a tool, which was developed for the
      comparison of diverse biomass-to-biofuel systems, in order to facilitate the cost
      wise decision making on this field.

PMID- 21074420
TI  - Characterization of primary thermal degradation features of lignocellulosic
      biomass after removal of inorganic metals by diverse solvents.
AB  - Poplar wood powders were treated with distilled water, tap water, HCl and HF,
      respectively, to remove inorganics from the biomass and to investigate effect of
      demineralization processes on pyrolysis behavior of the biomass. TG and DTG
      revealed that maximum degradation temperatures rose slightly from 362 degrees C
      for control to 372 degrees C, 366 degrees C and 368 degrees C after
      demineralization with distilled water, HCl and HF, respectively. Maximum
      degradation rates also increased from 0.96%/ degrees C for control to 1.15%/
      degrees C for HF-biomass, 1.23%/ degrees C for DI-H(2)O-biomass, and 1.55%/
      degrees C for HCl-biomass. Analytical pyrolysis-GC/MS of demineralized biomasses
      produced approximately 45 pyrolysis compounds. Total amount of low molecular
      weight compounds, such as acetic acid, acetol, and 3-hydroxypropanal, was
      significantly lowered in the demineralized biomasses. But levoglucosan increased
      2-10-folds in the demineralized biomasses. One of the features regarding lignin
      derivatives was the reduction of the amount of C6-type phenols, such as phenol,
      guaiacol, and syringol after demineralization.

PMID- 21074421
TI  - Effects of selected electron transport chain inhibitors on 24-h hydrogen
      production by Synechocystis sp. PCC 6803.
AB  - One factor limiting biosolar hydrogen (H(2)) production from cyanobacteria is
      electron availability to the hydrogenase enzyme. In order to optimize 24-h H(2)
      production this study used Response Surface Methodology and Q2, an optimization
      algorithm, to investigate the effects of five inhibitors of the photosynthetic
      and respiratory electron transport chains of Synechocystis sp. PCC 6803. Over 3
      days of diurnal light/dark cycling, with the optimized combination of 9.4 mM KCN
      (3.1 MUmol 10(10) cells(-1)) and 1.5 mM malonate (0.5 MUmol 10(10) cells(-1)) the
      H(2) production was 30-fold higher, in EHB-1 media previously optimized for
      nitrogen (N), sulfur (S), and carbon (C) concentrations (Burrows et al., 2008).
      In addition, glycogen concentration was measured over 24 h with two light/dark
      cycling regimes in both standard BG-11 and EHB-1 media. The results suggest that
      electron flow as well as glycogen accumulation should be optimized in systems
      engineered for maximal H(2) output.

PMID- 21074422
TI  - Partial nitritation and anammox of a livestock manure digester liquor and
      analysis of its microbial community.
AB  - A swim-bed reactor for partial nitritation with polymeric coagulant treatment and
      an UASB reactor for anammox were applied to the treatment of livestock manure
      digester liquor. The partial nitritation was maintained for 32 days under a 1.6
      kg N/m(3)/d nitrogen loading rate (NLR) with an average conversion efficiency of
      51%, and achieved 1.65 kg N/m(3)/d of the maximum nitrite production rate under
      2.58 kg N/m(3)/d of NLR. Although 200 mg/L of TOC remained in the effluent of the
      partial nitritation reactor, the anammox nitrogen removal rate was not
      significantly decreased and a relatively high rate of 2.0 kg N/m(3)/d was
      obtained under a NLR of 2.2 kg N/m(3)/d. 16S rRNA gene analysis showed that
      Nitrosomonas and KSU-1 were dominant in the partial nitritation and anammox
      reactor, respectively. The results of this study demonstrated that the partial
      nitritation-anammox process has possibility of applying to the nitrogen removal
      of livestock manure digester liquor.

PMID- 21074423
TI  - 4-deoxy-4-fluoro-xyloside derivatives as inhibitors of glycosaminoglycan
      biosynthesis.
AB  - Various 4-deoxy-4-fluoro-xylosides were prepared using click chemistry for
      evaluating their potential utility as inhibitors of glycosaminoglycan
      biosynthesis. 2,3-Di-O-benzoyl-4-deoxy-4-fluoro-beta-D-xylopyranosylazide,
      obtained from L-arabinopyranose by six steps, was treated with a wide variety of
      azide-reactive triple bond-containing hydrophobic agents in the presence of
      Cu(2+) salt/ascorbic acid, a step known as click chemistry. After click
      chemistry, benzoylated derivatives were deprotected under Zemplen conditions to
      obtain 4-deoxy-4-fluoro-xyloside derivatives. A mixture of alpha:beta-isomers of
      twelve derivatives were then separated on a reverse phase C18 column using HPLC
      and the resulting twenty four 4-deoxy-4-fluoro-xylosides were evaluated for their
      ability to inhibit glycosaminoglycan biosynthesis in endothelial cells. We
      identified two xyloside derivatives that selectively inhibit heparan sulfate and
      chondroitin sulfate/derman sulfate biosynthesis without affecting cell viability.
      These novel derivatives can potentially be used to define the biological actions
      of proteoglycans in model organisms and also as therapeutic agents to combat
      various human diseases in which glycosaminoglycans participate.

PMID- 21074424
TI  - Design, synthesis and SAR of thienopyridines as potent CHK1 inhibitors.
AB  - A novel series of CHK1 inhibitors based on thienopyridine template has been
      designed and synthesized. These inhibitors maintain critical hydrogen bonding
      with the hinge and conserved water in the ATP binding site. Several compounds
      show single digit nanomolar CHK1 activities. Compound 70 shows excellent
      enzymatic activity of 1 nM.

PMID- 21074425
TI  - In silico identification and biochemical evaluation of novel inhibitors of
      NRH:quinone oxidoreductase 2 (NQO2).
AB  - The NCI chemical database has been screened using in silico docking to identify
      novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Compounds identified
      from the screen exhibit a diverse range of scaffolds and inhibitory potencies are
      generally in the micromolar range. Some of the compounds also have the ability to
      inhibit NQO1. The modes of binding of the different compounds to the two enzymes
      are illustrated and discussed.

PMID- 21074426
TI  - The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2
      receptor antagonists.
AB  - The identification and subsequent optimisation of a selective non-peptidic NPY Y2
      antagonist series is described. This led to the development of amine 2, a
      selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure.

PMID- 21074427
TI  - Green synthesis and biological evaluation of some novel azoles as antimicrobial
      agents.
AB  - A series of novel fluorine-containing triazoles 3, thiadiazoles 4, and
      oxadiazoles 5 were synthesized from thiosemicarbazides 2. These reactions were
      carried out by green technique such as ultrasonication and microwave. All
      products have been characterized by IR, (1)H NMR, and Mass spectral study and
      screened for their antimicrobial activity.

PMID- 21074428
TI  - The discovery and structure-activity relationships of indole-based inhibitors of
      glutamate carboxypeptidase II.
AB  - A series of N-substituted 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acids were
      synthesized as inhibitors of glutamate carboxypeptidase II (GCPII). Those
      containing carboxybenzyl or carboxyphenyl groups at the N-position exhibited
      potent inhibitory activity against GCPII. These indole-based compounds represent
      the first example of achiral GCPII inhibitors and demonstrate greater tolerance
      of the GCPII active site for ligands with significant structural difference from
      the endogenous substrate, N-acetyl-aspartylglutamate.

PMID- 21074429
TI  - Synthesis and biological evaluation of 1H-benzimidazol-5-ols as potent HBV
      inhibitors.
AB  - A new series of 1-methyl-1H-benzimidazol-5-ol derivatives were synthesized and
      evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the
      HepG2.2.15 cell line. Some of the analogues in this series displayed inhibitory
      activity superior to lamivudine. Of them, compound 13b was the most potent one,
      showing an IC(50) value of 7.8 MUM and a SI value of 13.0.

PMID- 21074430
TI  - Discovery of new chemotype dipeptidyl peptidase IV inhibitors having (R)-3-amino
      3-methyl piperidine as a pharmacophore.
AB  - Structures containing the (R)-3-amino-3-methyl piperidine unit as a new
      pharmacophore moiety have been shown to possess moderate inhibitory activity for
      DPP-4 with good pharmacokinetics profile. One of these compounds was found to
      have good oral bioavailability and PK/PD profile in ZF-rat.

PMID- 21074431
TI  - Design and synthesis of harzialactone analogues: promising anticancer agents.
AB  - New homologues of harzialactone were synthesized using D-glucose as chiral
      template. Wittig reaction to introduce aromatic moiety in 10 and chemoselective
      anomeric oxidation of 13 were used as key reactions in our synthesis. Anticancer
      activity of these target molecules was assessed against five cancer cell lines,
      P388D1, HL60, COLO-205, Zr-75-1 and HeLa. Both compound 5 and 6, showed
      significant activity against colon cancer (COLO-205) and cervical cancer (HeLa)
      and moderate with others. To the best of our knowledge, this is the first report
      of harzialactone analogues as potent inhibitors of human colon and cervical
      cancer.

PMID- 21074432
TI  - Selective peroxisome proliferator-activated receptor delta isosteric selenium
      agonists as potent anti-atherogenic agents in vivo.
AB  - We report the synthesis and in vivo activity of a novel anti-atherogenic agent,
      isosteric selenium PPARdelta-selective ligand. This ligand did not cause
      significant body or liver weight changes and did not have obvious adverse effects
      on intestinal polyp formation. Our overall results clearly demonstrate that
      PPARdelta is a viable drug candidate for targeting and treating atherosclerosis.

PMID- 21074433
TI  - 3,5-disubstituted pyranone analogues of highly antifungally active furanones:
      conversion of biological effect from antifungal to cytostatic.
AB  - A series of 3-aryl-5-acyloxymethyl-5,6-dihydro-2H-pyran-2-ones, related to highly
      antifungally active butenolides, was synthesized via cyclization of substituted
      delta-hydroxy acids as the key step, and evaluated for their in vitro antifungal
      activity and cytostatic activity. While the extension of the furanone ring to
      pyranone led to a complete loss of the antifungal effect, some of the compounds
      displayed promising effect against several cell lines, including the resistant
      colorectal carcinoma cells.

PMID- 21074434
TI  - Design, synthesis, and structure-activity relationship study of bicyclic
      piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor
      agonists.
AB  - Bicyclic piperazine derivatives were synthesized as conformationally constrained
      analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists.
      The CB1 receptor agonist activity was dependent upon the absolute configuration
      of the chiral center of the bicyclic ring system. Although the conformational
      constraint did not protect the compounds from metabolism by N-dealkylation,
      several bicyclic analogs were found to be more potent than the unconstrained lead
      compound. Compound 8b demonstrated potent antinociceptive activity in vivo.

PMID- 21074435
TI  - Pyridylmethylthio derivatives as VEGF inhibitors. Part 1.
AB  - Optimization from compound 4a, having intramolecular S-O nonbonded interaction,
      led to discover compounds 4m and 4n. They were highly active in vitro (VEGF
      induced HUVEC proliferation assay) and showed efficacies in three disease models
      in vivo (cancer, RA, AMD).

PMID- 21074436
TI  - Discovery of NBI-77860/GSK561679, a potent corticotropin-releasing factor (CRF1)
      receptor antagonist with improved pharmacokinetic properties.
AB  - Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove
      effective in treating stress and anxiety related disorders. In an effort to
      identify antagonists with improved physico-chemical properties a new series of
      CRF(1) antagonists were designed to substitute the propyl groups at the C7
      position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound
      (S)-8d was identified as a high affinity ligand with a pK(i) value of 8.2 and a
      functional CRF(1) antagonist with pIC(50) value of 7.0 in the in vitro CRF ACTH
      production assay.

PMID- 21074437
TI  - The value of latissimus dorsi flap with implant reconstruction for total
      mastectomy after conservative breast cancer surgery recurrence.
AB  - Total mastectomy is usually indicated after breast conservative treatment cancer
      recurrence. Breast reconstruction in this group can be performed with many
      options. We did 63 latissimus dorsi flap with implants reconstructions between
      2001-2007. All of them were performed in breast cancer recurrence cases after
      breast conservative treatment and preceded for total mastectomy. The patient age
      range from 31 to 71 years old (50.1 +/- 7.3 years). The follow-up was 36.5 +/-
      14.9 months (22-141 months). Neither flap loss nor significant major donor-site
      complication was recorded. The capsular contraction Baker's grade III was
      observed in 2 cases (3.1%). The rest were grade I-II and there was no grade IV
      contracture. We purpose that LD flap with implant can be performed in irradiated
      breast with low capsular contracture rate. It is suitable in total mastectomy
      reconstruction after conservative breast cancer surgery recurrence.

PMID- 21074438
TI  - TAp73 acts via the bHLH Hey2 to promote long-term maintenance of neural
      precursors.
AB  - Increasing evidence suggests that deficits in adult stem cell maintenance cause
      aberrant tissue repair and premature aging [1]. While the mechanisms regulating
      stem cell longevity are largely unknown, recent studies have implicated p53 and
      its family member p63. Both proteins regulate organismal aging [2-4] as well as
      survival and self-renewal of tissue stem cells [5-9]. Intriguingly,
      haploinsufficiency for a third family member, p73, causes age-related
      neurodegeneration [10]. While this phenotype is at least partially due to loss of
      the DeltaNp73 isoform, a potent neuronal prosurvival protein [11-16], a recent
      study showed that mice lacking the other p73 isoform, TAp73, have perturbations
      in the hippocampal dentate gyrus [17], a major neurogenic site in the adult
      brain. These findings, and the link between the p53 family, stem cells, and
      aging, suggest that TAp73 might play a previously unanticipated role in
      maintenance of neural stem cells. Here, we have tested this hypothesis and show
      that TAp73 ensures normal adult neurogenesis by promoting the long-term
      maintenance of neural stem cells. Moreover, we show that TAp73 does this by
      transcriptionally regulating the bHLH Hey2, which itself promotes neural
      precursor maintenance by preventing premature differentiation.

PMID- 21074439
TI  - Developmental control of late replication and S phase length.
AB  - BACKGROUND: Fast, early embryonic cell cycles have correspondingly fast S phases.
      In early Drosophila embryos, forks starting from closely spaced origins replicate
      the whole genome in 3.4 min, ten times faster than in embryonic cycle 14 and a
      hundred times faster than in a wing disc. It is not known how S phase duration is
      regulated. Here we examined prolongation of embryonic S phases, its coupling to
      development, and its relationship to the appearance of heterochromatin. RESULTS:
      Imaging of fluorescent nucleotide incorporation and GFP-PCNA gave exquisite time
      resolution of S phase events. In the early S phases, satellite sequences
      replicated rapidly despite a compact chromatin structure. In S phases 11-13, a
      delay in satellite replication emerged in sync with modest and progressive
      prolongation of S phase. In S phase 14, major and distinct delays ordered the
      replication of satellites into a sequence that occupied much of S phase. This
      onset of late replication required transcription. Satellites only accumulated
      abundant heterochromatin protein 1 (HP1) after replicating in S phase 14. By
      cycle 15, satellites clustered in a compact HP1-positive mass, but replication
      occurred at decondensed foci at the surface of this mass. CONCLUSIONS: The
      slowing of S phase is an active process, not a titration of maternal replication
      machinery. Most sequences continue to replicate rapidly in successive cycles, but
      increasing delays in the replication of satellite sequences extend S phase.
      Although called constitutively heterochromatic, satellites acquire the
      distinctive features of heterochromatin, compaction, late replication, HP1
      binding, and aggregation at the chromocenter, in successive steps coordinated
      with developmental progress.

PMID- 21074440
TI  - Demographic history of Oceania inferred from genome-wide data.
AB  - BACKGROUND: The human history of Oceania comprises two extremes: the initial
      colonizations of Near Oceania, one of the oldest out-of-Africa migrations, and of
      Remote Oceania, the most recent expansion into unoccupied territories. Genetic
      studies, mostly using uniparentally inherited DNA, have shed some light on human
      origins in Oceania, particularly indicating that Polynesians are of mixed East
      Asian and Near Oceanian ancestry. Here, we use ~1 million single nucleotide
      polymorphisms (SNPs) to investigate the demographic history of Oceania in a more
      detailed manner. RESULTS: We developed a new approach to account for SNP
      ascertainment bias, used approximate Bayesian computation simulations to choose
      the best-fitting model of population history, and estimated demographic
      parameters. We find that the ancestors of Near Oceanians diverged from ancestral
      Eurasians ~27 thousand years ago (kya), suggesting separate initial occupations
      of both territories. The genetic admixture in Polynesian history between East
      Asians (~87%) and Near Oceanians (~13%) occurred ~3 kya, prior to the
      colonization of Polynesia. Fijians are of Polynesian (~65%) and additional Near
      Oceanian (~35%) ancestry not found in Polynesians, with this admixture occurring
      considerably after the initial settlement of Remote Oceania. Our data support a
      greater contribution of East Asian women than men in the admixture history of
      Remote Oceania and highlight population substructure in Polynesia and New Guinea.
      CONCLUSIONS: Despite the inherent ascertainment bias, genome-wide SNP data
      provide new insights into the genetic history of Oceana. Our approach to correct
      for ascertainment bias and obtain reliable inferences concerning demographic
      history should prove useful in other such studies.

PMID- 21074442
TI  - Effects of an ankle-foot orthosis with oil damper on muscle activity in adults
      after stroke.
AB  - BACKGROUND AND OBJECTIVE: An ankle-foot orthosis with an oil damper (AFO-OD) was
      developed to resist plantarflexion motion, thereby improving hemiplegic gait
      performance. The purpose of this study was to determine the effect of AFO-OD on
      muscle activity during the gait cycle in individuals affected by stroke. METHODS:
      Electromyography (EMG) was used to assess gait at a self-selected speed while
      wearing an AFO-OD or an AFO with a plantarflexion stop (AFO-PS) worn on the
      affected side in 11 stroke survivors and on the right side in 11 age-matched
      healthy adults. EMG signals were obtained from the tibialis anterior (TA),
      gastrocnemius (GAS), and soleus (SOL) muscles. In addition, the ankle joint angle
      under both braces and the plantarflexion resistance torque (PFRT) under AFO-OD
      were monitored. RESULTS: Peak PFRT under AFO-OD was observed during the loading
      response phase (LRP) in both groups. AFO-OD promoted adequate plantarflexion
      during LRP in the stroke group, whereas AFO-PS did not. Compared with the AFO-PS,
      the AFO-OD significantly reduced GAS EMG amplitude during LRP in the stroke
      group, which was significantly correlated with peak PFRT during LRP. CONCLUSION:
      AFO-OD assisted the "heel rocker function" and reduced GAS muscle EMG amplitude
      during LRP.

PMID- 21074443
TI  - Convergent synthesis of fluorescence-labeled probes of Annonaceous acetogenins
      and visualization of their cell distribution.
AB  - The convergent synthesis of fluorescence-labeled solamin, an antitumor
      Annonaceous acetogenin, was accomplished by two asymmetric alkynylations of 2,5
      diformyl tetrahydrofuran with an alkyne tagged with fluorescent groups and
      another alkyne with an alpha,beta-unsaturated gamma-lactone. Assay for the growth
      inhibitory activity against human cancer cell lines revealed that the probe with
      the fluorescent groups at the end of the hydrocarbon chain may have the same mode
      of action as natural acetogenins. The merged fluorescence of dansyl-labeled
      solamin and MitoTracker Red suggests that Annonaceous acetogenins localize in the
      mitochondria.

PMID- 21074441
TI  - Inactive yet indispensable: the tale of Jarid2.
AB  - Methylation of histone tails is believed to be important for the establishment
      and inheritance of gene expression programs during development. Jarid2/Jumonji is
      the founding member of a family of chromatin modifiers with histone demethylase
      activity. Although Jarid2 contains amino acid substitutions that are thought to
      abolish its catalytic activity, it is essential for the development of multiple
      organs in mice. Recent studies have shown that Jarid2 is a component of the
      polycomb repressive complex 2 and is required for embryonic stem (ES) cell
      differentiation. Here, we discuss current literature on the function of Jarid2
      and hypothesize that defects resulting from Jarid2 deficiency arise from a
      failure to correctly prime genes in ES cells that are required for later stages
      in development.

PMID- 21074444
TI  - Synthesis of 4beta-N-polyaromatic substituted podophyllotoxins: DNA topoisomerase
      inhibition, anticancer and apoptosis-inducing activities.
AB  - A new class of 4beta-N-polyaromatic substituted podophyllotoxin congeners have
      been synthesized and evaluated for their DNA topoisomerase-II (topo-II)
      inhibition as well as anticancer potential in some human cancer cell lines. The
      ease of synthesis and interesting biological activities make the present series
      of polyaromatic-podophyllotoxin congeners as a promising new structure for the
      development of new anticancer agents based on podophyllotoxin scaffold.

PMID- 21074445
TI  - A portable Compton spectrometer for clinical X-ray beams in the energy range 20
      150 keV.
AB  - Primary beam spectra were obtained for an X-ray industrial equipment (40-150 kV),
      and for a clinical mammography apparatus (25-35 kV) from beams scattered at
      angles close to 90 degrees , measured with a CdTe Compton spectrometer. Actual
      scattering angles were determined from the Compton energy shift of characteristic
      X-rays or spectra end-point energy. Evaluated contribution of coherent scattering
      amounts to more than 15% of fluence in mammographic beams. This technique can be
      used in clinical environments.

PMID- 21074446
TI  - New modified expressions for isothermal decay of Teflon embedded LiF:Mg,Cu,P and
      BaSO4:Eu phosphors.
AB  - This paper gives a full mathematical description of the kinetics expressions used
      in thermoluminescent isothermal decay experiments. The corresponding equations
      have been slightly modified considering the peak intensity at the maximum (I(M))
      instead of the peak area Phi as proportional to absorbed dose, given normally in
      isothermal decay equations. The isothermal decay method was applied to the
      principal glow peaks of two different phosphors: LiF:Mg,Cu,P+PTFE, using first-
      and second-order kinetics, and BaSO(4):Eu+PTFE, using second-order kinetics.

PMID- 21074447
TI  - Antioxidants in Erica andevalensis: a comparative study between wild plants and
      cadmium-exposed plants under controlled conditions.
AB  - Erica andevalensis is an endemic species from SW Iberian Peninsula, always
      growing in metal-enriched and acid soils. In the present study, a comparison was
      made between wild E. andevalensis plants collected from the field and cultivated
      ones exposed to different cadmium levels (0, 0.5, 5 and 50 MUM). Wild plants
      contain higher levels of ascorbic acid (around 8000 nmol g(-1) FW) than lab
      cultivated control plants (around 3000 nmol g(-1) FW). Glutathione levels follow
      an opposite trend being smaller in wild plants than lab-cultivated ones.
      Moreover, the total antioxidant capacity of wild plants is 90 times higher than
      in cultivated plants non-exposed to cadmium. Cadmium treatment of lab-cultivated
      plants did not affect the growth of E. andevalensis or the glutathione levels.
      However, the total antioxidative capacity increased in plants exposed to 50 MUM
      of cadmium. Cadmium was added to the soil and it was transported into leaves
      reaching levels of 3.299 +/- 0.781 MUg Cd/g DW in plants exposed to 50 MUM. These
      results underline a possible importance of antioxidants in the metal tolerance
      show by the high antioxidant capacity detected in both wild and lab-cultivated
      plants exposed to high cadmium levels.

PMID- 21074448
TI  - Differential regulation of 3-aminomethylindole/N-methyl-3-aminomethylindole N
      methyltransferase and gramine in barley by both biotic and abiotic stress
      conditions.
AB  - The expression of NMT (3-aminomethylindole/N-methyl-3-aminomethylindole N
      methyltransferase; EC 2.1.1.), involved in the biosynthesis of the indole
      alkaloid gramine, was investigated in aphid-infested barley (Hordeum vulgare L.).
      NMT is induced by methyl jasmonate and it was hypothesized that the gene would be
      more strongly upregulated in aphid-resistant barley. We examined the effects of
      feeding by three aphid species; Russian wheat aphid (Diuraphis noxia Mordvilko),
      rose-grain aphid (Metopolophium dirhodum Walker) and bird cherry-oat aphid
      (Rhopalosiphum padi L.) on barley genotypes with varying resistance
      characteristics. The barley genotypes selected included the cultivar Libra, known
      to upregulate gramine after feeding by Schizaphis graminum. Infestation by R.
      padi and M. dirhodum resulted in higher NMT expression in the doubled haploid
      line 5172-28:4 (DH28:4), which has moderate resistance against R. padi, but not
      in other aphid-barley combinations. None of the aphid-plant combinations had
      however increased gramine, suggesting that aphid-induction of gramine is specific
      to S. graminum. The increased abundance of NMT transcript in aphid-infested
      DH28:4 did not lead to higher amounts of NMT protein or NMT enzyme activity,
      neither did 200 times upregulation of NMT transcript in cotyledons incubated with
      methyl jasmonate, illustrating that even large differences measured at transcript
      level may have no metabolic consequences. Drought stress or treatments with
      abscisic acid did lead to higher gramine concentrations in several barley
      cultivars, but without any concomitant increase of NMT transcripts. Thus, the
      regulation of the biosynthetic pathway to gramine at transcript and metabolite
      level diverges during two different stress conditions.

PMID- 21074449
TI  - Descending necrotizing mediastinitis following dental extraction. Radiological
      features and surgical treatment considerations.
AB  - Descending necrotizing mediastinitis (DNM) following dental extraction is an
      extremely serious infection with a high mortality rate. Oral infection may
      rapidly descend into the mediastinum across the retropharyngeal and retrovisceral
      spaces. Once established, mediastinitis is rapidly followed by sepsis and death.
      If DNM is suspected cervical and thoracic CT must be carried out urgently. After
      this, prompt control of the upper airway with tracheostomy, aggressive surgical
      debridement of the deep cervical spaces and mediastinum, and intravenous broad
      spectrum antibiotic therapy are mandatory. The present paper reports two new
      cases of DNM following dental extraction, and focuses on radiological features of
      abscess progression through the cervical spaces down into the mediastinum.

PMID- 21074450
TI  - Distraction osteogenesis as followed by CT scan in Pierre Robin sequence.
AB  - THE AIM: The aim of this work was to assess the multislice CT scan for analysis
      of the craniofacial anatomic changes in Pierre Robin sequence both predistraction
      and postdistraction, and to assess the use of unidirectional internal distractors
      in this patient group. PATIENTS & METHODS: The study involved 11 patients. Their
      age at the time of distraction ranged from 2 to 7 months. Six were females and 5
      were males. All had retromicrognathia, glossoptosis and obstructive sleep apnoea.
      All were diagnosed clinically and by CT scan. All were managed by distraction
      osteogenesis and were followed postoperatively by multislice CT. RESULTS: The
      distance between the base of the tongue and the posterior pharyngeal wall
      increased by a mean of 141%, and the total mandibular length increased by a mean
      of 26%. The increase in the distance between the hyoid bone and the posterior
      pharyngeal wall increased by a mean of 42% .The distance between the hyoid bone
      and the genoid process increased by a mean of 9%. CONCLUSION: Multislice CT scan
      was found to be a practical imaging technique to evaluate the morphologic changes
      in the airway and the mandible after distraction osteogenesis. It rules out the
      need for other traditional methods. Owing to the plasticity and malleability of
      the infant mandible that allow for sufficient bone remodelling, unidirectional
      internal distractors achieved a satisfactory maxillomandibular relationship which
      was tolerated by the infants and accepted by the parents.

PMID- 21074451
TI  - Primary synovial sarcoma of the parotid gland in 15-year-old boy.
AB  - Synovial sarcoma (SS) is a malignant mesenchymal tumour, predominantly found in
      the deep soft tissues of lower extremities, whereas only 3% occur in the head and
      neck region. Primary synovial sarcoma of the parotid gland is exceptionally
      uncommon. This is a report of a 15-year-old boy with a synovial sarcoma arising
      in the parotid gland, and, to the best of our knowledge, this is the youngest
      patient on record. The patient was treated primarily surgically, followed by
      chemotherapy and radiotherapy. Two years after this multimodal therapy, the
      patient is without signs of loco-regional recurrence or distant metastases. This
      paper highlights the importance of a multidisciplinary approach in the diagnosis
      and treatment of this very rare entity.

PMID- 21074452
TI  - Molecular assessment of UVC radiation-induced DNA damage repair in the
      stromatolitic halophilic archaeon, Halococcus hamelinensis.
AB  - The halophilic archaeon Halococcus hamelinensis was isolated from living
      stromatolites in Shark Bay, Western Australia, that are known to be exposed to
      extreme conditions of salinity, desiccation, and UV radiation. Modern
      stromatolites are considered analogues of very early life on Earth and thus
      inhabitants of modern stromatolites, and Hcc. hamelinensis in particular, are
      excellent candidates to examine responses to high UV radiation. This organism was
      exposed to high dosages (up to 500 J/m(2)) of standard germicidal UVC (254 nm)
      radiation and overall responses such as survival, thymine-thymine cyclobutane
      pyrimidine dimer formation, and DNA repair have been assessed. Results show that
      Hcc. hamelinensis is able to survive high UVC radiation dosages and that intact
      cells give an increased level of DNA protection over purified DNA. The organism
      was screened for the bacterial-like nucleotide excision repair (NER) genes uvrA,
      uvrB, uvrC, as well as for the photolyase phr2 gene. All four genes were
      discovered and changes in the expression levels of those genes during repair in
      either light or dark were investigated by means of quantitative Real-Time (qRT)
      PCR. The data obtained and presented in this study show that the uvrA, uvrB, and
      uvrC genes were up-regulated during both repair conditions. The photolyase phr2
      was not induced during dark repair, yet showed a 20-fold increase during repair
      in light conditions. The data presented is the first molecular study of different
      repair mechanisms in the genus Halococcus following exposure to high UVC
      radiation levels.

PMID- 21074453
TI  - A qualitative exploration of nurse's perception of Critical Outreach Service: a
      before and after study.
AB  - BACKGROUND: Critical Care Outreach Services (CCOS) have been reported to
      streamline the transfer of patients from the intensive care unit (ICU) to the
      wards and provide a follow-up service supporting ward staff to provide optimum
      care for patients discharged from ICU. PURPOSE: The aim of this study was to
      explore the perceptions of nursing staff before and after the introduction of a
      CCOS at three adult teaching hospitals in Perth, Western Australia. METHODS:
      Exploratory focus groups were conducted with registered nurses (RNs) at each of
      the participating hospitals prior to and 6 months after the introduction of a
      CCOS. Framework analysis was used to analyse the transcribed data using a
      thematic approach with themes developed from the narratives of the participants.
      RESULTS: Inexperienced RNs in particular voiced positive comments about the CCOS.
      The role was seen as a senior nurse who was an additional resource for less
      experienced staff as they educated them on complex procedures that were not
      common on the general wards. The RNs reported that apprehensions about the role
      that they had pre-implementation were not borne out in practice and that they
      believed that the CCOS had positive effects on patient outcomes. CONCLUSION: The
      CCOS improved communication processes between members of the multidisciplinary
      team and units within the hospital, which subsequently enhanced the ward
      transition process for critically ill patients and ward nursing staff.

PMID- 21074454
TI  - Induction of IL-13 production and upregulated expression of protease activated
      receptor-1 by RANTES in a mast cell line.
AB  - RANTES is a potent chemoattractant for various important inflammatory cells such
      as eosinophils, memory T cells and mast cells. It has been long recognized as a
      crucial player in the pathogenesis of allergy. However, little is known of its
      effects on cytokine secretion and protease activated receptor (PAR) expression in
      mast cells. In the present study, we examined potential influence of RANTES on IL
      13 and IL-12 release from P815 cells and PAR expression on P815 cells by using
      flow cytometry analysis, quantitative real-time PCR, ELISA and cellular
      activation of signaling ELISA (CASE) techniques. The results showed that RANTES
      induced up to 2.2-fold increase in IL-13, but not IL-12 release from P815 cells.
      Blocking antibodies against RANTES and CCR5 diminished RANTES induced IL-13
      release. Furthermore, RANTES upregulated expression of PAR-1, PAR-2 and PAR-3
      mRNAs, but enhanced only PAR-1 protein expression. At 1 ng/ml, RANTES can abolish
      tryptase induced IL-13 release, but enhance trypsin, tryptase and thrombin
      induced PAR-1, -2 and -4 expression. LY204002 abolished RANTES induced IL-13
      release, indicating an Akt cell signaling pathway may be involved in the event.
      In conclusion, RANTES can stimulate IL-13 release from mast cells through a CCR5
      and Akt cell signaling pathway dependent mechanism. It can also enhance trypsin,
      tryptase and thrombin-induced expression of PARs in mast cells. RANTES may
      contribute to modulation of IL-13 production and PAR expression in mast cells,
      through which participates in the mast cell related inflammation.

PMID- 21074455
TI  - What needs to change: goals for clinical and social management and research in
      the next 60 years.
AB  - While substantial progress over the past 60 years has enabled a greater
      proportion of persons with epilepsy (PWE) to live without seizures and treatment
      related side effects, numerous challenges in the diagnosis, treatment and social
      management of epilepsy remain to be solved over the next 60 years so that no
      person with epilepsy is limited by any aspect of the condition. This achievement
      is within our reach, but will require professional and lay epilepsy organisations
      to work closely together to ensure that clinical, scientific and sociological
      advances are made and applied to the medical and social management of epilepsy.

PMID- 21074456
TI  - Surviving brain surgery.

PMID- 21074457
TI  - Anticonvulsant activities of myo-inositol and scyllo-inositol on
      pentylenetetrazol induced seizures.
AB  - Myo-inositol (MI) and its isomers are used for the treatment of various
      neuropathological conditions. The purpose of the present research was to study
      anticonvulsant properties of MI and scyllo-inositol (SCI) on pentylenetetrazol
      (PTZ) induced seizures in rats. Half an hour after treatment with MI (30 mg/kg)
      or SCI (5 mg/kg) seizures were induced in Wistar rats with PTZ (60 mg/kg).
      Control animals were treated either by normal saline or mannitol (control polyol
      of the same molecular weight, 30 mg/kg), given at the same time interval before
      PTZ injection, as MI/SCI groups. The anticonvulsant effects of MI/SCI treatment
      were assessed by the latent period (the time from PTZ-injection to the onset of
      first seizures), and the duration and severity (score) of seizures. The mortality
      rate was also assessed. Both MI and SCI treatment significantly reduced the
      seizure score, seizure duration and increased the latent period. These data
      suggest for strong potential of MI and SCI as the agents of antiepileptic
      therapy.

PMID- 21074458
TI  - Medical management: from colony to community.
AB  - In this article the development from the colonies founded in the 19th century to
      the current situation is discussed. Future development is not to simply follow
      the slogan 'to the community' translated as 'epilepsy must be treated in general
      hospitals' but to preserve epileptology as specialized care with 'centres of
      excellence' orchestrated by coupling epilepsy centres with academical neurology.

PMID- 21074459
TI  - The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular
      double-stranded DNA.
AB  - The innate immune system detects pathogen- and host-derived double-stranded DNA
      exposed to the cytosol and induces type I interferon (IFN) and other cytokines.
      Here, we identified interferon-inducible tripartite-motif (TRIM) 56 as a
      regulator of double-stranded DNA-mediated type I interferon induction. TRIM56
      overexpression enhanced IFN-beta promoter activation after double-stranded DNA
      stimulation whereas TRIM56 knockdown abrogated it. TRIM56 interacted with STING
      and targeted it for lysine 63-linked ubiquitination. This modification induced
      STING dimerization, which was a prerequisite for recruitment of the antiviral
      kinase TBK1 and subsequent induction of IFN-beta. Taken together, these results
      indicate that TRIM56 is an interferon-inducible E3 ubiquitin ligase that
      modulates STING to confer double-stranded DNA-mediated innate immune responses.

PMID- 21074461
TI  - Descending thoracic endovascular aneurysm repair: antegrade approach via
      ascending aortic conduit.
AB  - Challenging access situations continue to arise in endovascular aneurysm repair,
      despite evolving arterial access techniques. We report a modified access
      approach, where an ascending aortic conduit was successfully used for antegrade
      delivery of a thoracic endograft to repair a descending thoracic aortic aneurysm,
      in a patient with previous surgical ligation of the infra-renal aorta.

PMID- 21074460
TI  - T regulatory cells maintain intestinal homeostasis by suppressing gammadelta T
      cells.
AB  - Immune tolerance against enteric commensal bacteria is important for preventing
      intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1
      (Pdk1) in T cells via Cd4-Cre induced chronic inflammation of the intestine
      despite the importance of PDK1 in T cell activation. Analysis of colonic
      intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased
      CD8alpha(+) T cell receptor (TCR)gammadelta(+) T cells, including an interleukin
      17 (IL-17)-expressing population. TCRgammadelta(+) T cells were responsible for
      the inflammatory colitis as shown by the fact that deletion of Tcrd abolished
      spontaneous colitis in the PDK1-deficient mice. This dysregulation of intestinal
      TCRgammadelta(+) T cells was attributable to a reduction in the number and
      functional capacity of PDK1-deficient T regulatory (Treg) cells. Adoptive
      transfer of wild-type Treg cells abrogated the spontaneous activation and
      proliferation of intestinal TCRgammadelta(+) T cells observed in PDK1-deficient
      mice and prevented the development of colitis. Therefore, suppression of
      intestinal TCRgammadelta(+) T cells by Treg cells maintains enteric immune
      tolerance.

PMID- 21074462
TI  - The influence of orthognathic surgery on upper airway function is still unknown.

PMID- 21074463
TI  - Treatment of ankylosed maxillary central incisors by single-tooth dento-osseous
      osteotomy and alveolar bone distraction.
AB  - When tooth ankylosis occurs in growing children, the ankylosed tooth fails to
      erupt and gradually positions itself below the occlusal plane. This causes
      functional and esthetic problems, and orthodontic treatment is often impossible.
      To clarify this problem, we developed a new treatment protocol for the movement
      of ankylosed teeth. This consists of single-tooth dento-osseous osteotomy and
      alveolar bone distraction using orthodontic multibracket appliances. A special
      distraction device is not required, thus reducing the burden to patients. Two
      cases in which an ankylosed maxillary central incisor was successfully treated
      with this protocol are presented.

PMID- 21074464
TI  - Childhood posterior reversible encephalopathy syndrome.
AB  - Posterior Reversible Encephalopathy Syndrome (PRES) is a clinicoradiologic
      syndrome characterised clinically by headaches, altered consciousness, visual
      disturbances and seizures and radiological changes which can resolve. However
      left untreated it can be fatal and not all cases are reversible. It can occur in
      many settings, the most common being hypertensive crisis. We discuss the clinical
      and radiological features of this increasingly diagnosed condition among children
      and current thinking on its pathogenesis. A brief case is used to highlight the
      variable presentation of PRES. PRES is often unsuspected by the clinician and
      radiologists may be first to suggest the diagnosis. Accurate assessment including
      blood pressure measurement, appropriate imaging and rapid treatment is required
      to avoid a devastating outcome.

PMID- 21074465
TI  - Structure of the two-dimensional relaxation spectra seen within the eigenmode
      perturbation theory and the two-site exchange model.
AB  - The form of the two-dimensional (2D) NMR-relaxation spectra--which allow to study
      interstitial fluid dynamics in diffusive systems by correlating spin-lattice
      (T(1)) and spin-spin (T(2)) relaxation times--has given rise to numerous
      conjectures. Herein we find analytically a number of fundamental structural
      properties of the spectra: within the eigen-modes formalism, we establish
      relationships between the signs and intensities of the diagonal and cross-peaks
      in spectra obtained by various 1 and 2D NMR-relaxation techniques, reveal
      symmetries of the spectra and uncover interdependence between them. We
      investigate more specifically a practically important case of porous system that
      has sets of T(1)- and T(2)-eigenmodes and eigentimes similar to each other by
      applying the perturbation theory. Furthermore we provide a comparative analysis
      of the application of the, mathematically more rigorous, eigen-modes formalism
      and the, rather more phenomenological, first-order two-site exchange model to
      diffusive systems. Finally we put the results that we could formulate
      analytically to the test by comparing them with computer-simulations for 2D
      porous model systems. The structural properties, in general, are to provide
      useful clues for assignment and analysis of relaxation spectra. The most striking
      of them--the presence of negative peaks--underlines an urgent need for
      improvement of the current 2D Inverse Laplace Transform (ILT) algorithm used for
      calculation of relaxation spectra from NMR raw data.

PMID- 21074466
TI  - Disturbed apolipoprotein A-I-containing lipoproteins in fish-eye disease are
      improved by the lecithin:cholesterol acyltransferase produced by gene-transduced
      adipocytes in vitro.
AB  - We report the in vitro efficacy of recombinant LCAT produced by lcat gene
      transduced proliferative adipocytes (ccdPA/lcat), which has been developed for
      enzyme replacement therapy. ApoA-I-specific immunodetection in combination with
      1D and 2D gel electrophoreses showed that the disturbed high-density lipoprotein
      subpopulation profile was clearly ameliorated by the in vitro incubation with
      ccdPA/lcat-derived recombinant LCAT. Thus, these results using ccdPA/lcat
      strongly suggest the cell implantation could contribute the enzyme replacement
      for the patients with LCAT deficiency.

PMID- 21074467
TI  - Beam configuration and physical parameters of clinical high energy photon beam
      for total body irradiation (TBI).
AB  - PURPOSE: To start total body irradiation (TBI) treatments, physical parameters
      are measured for a magna field irradiation. METHODS AND MATERIALS: 6 MV photon
      beam from Clinac 600 CD linear accelerator (Varian, USA) with fully opened
      collimator at 45 degrees  and gantry at 270 degrees  provided a diamond shaped
      magna field with diagonal dimension 224 cm at 4.0 m source skin distance (SSD).
      The flatness of the radiation field was measured in the presence of locally
      designed acrylic beam spoiler and beam flatness filter. Central Axis Depth dose
      data (CADD), tissue maximum ratios and entrance dose pattern are measured using
      large phantoms. Methods for clinical dose estimation using semi-conductor diodes
      and TLD were standardized. RESULTS: PVC beam flattener at the shielding tray
      position and the presence of acrylic beam spoiler in the radiation field provided
      a flatness of 100.15% +/- 0.44% compared to open beam flatness 101.6 +/- 1.5%. A
      reduction of 2% in percentage depth dose was observed at 10 cm depth in the
      presence of 15 mm acrylic beam spoiler. However, no changes are observed in the
      TMRs with presence of beam spoiler. The measured ionization ratios clearly showed
      change of beam quality with the introduction of beam spoiler. The presence of 15
      mm beam spoiler ensured entrance dose 100% at skin and remaining unchanged within
      1% upto a depth of 10 mm. Phantom measurements show good agreement between
      calculated and measured doses. CONCLUSIONS: The paper recommends use of modified
      CADD parameters for treatment planning, if calibration of output is carried out
      in the presence of beam spoiler.

PMID- 21074468
TI  - Online beam monitoring in the treatment of ocular pathologies at the INFN
      Laboratori Nazionali del Sud-Catania.
AB  - A detector (MOPI) has been developed for the online monitoring of the beam at the
      Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA), where shallow
      tumours of the ocular region are treated with 62 MeV protons. At CATANA the beam
      is passively spread to match the tumour shape. The uniformity of the delivered
      dose depends on beam geometrical quantities which are checked before each
      treatment. However, beam instabilities might develop during the irradiation
      affecting the dose distribution. This paper reports on the use of the MOPI
      detector to measure the stability of the beam profile during the irradiation in
      the clinical practice. The results obtained in the treatment of 54 patients are
      also presented.

PMID- 21074469
TI  - Proposed local diagnostic reference levels in angiography and interventional
      neuroradiology and a preliminary analysis according to the complexity of the
      procedures.
AB  - The aim of this study was to propose local diagnostic reference levels (DRL) for
      exposure to radiation during diagnostic procedures and neuroradiological
      interventions such as cerebral angiography and embolisation of cerebral aneurysms
      (intra-cranial aneurysms and arteriovenous malformations). Hospitals should adopt
      the national DRLs for use locally or establish their own DRLs based on local
      practice, if sufficient local data are available. For this purpose we studied a
      sample of 113 cerebral angiography procedures and 82 embolisations of cerebral
      aneurysms. The data recorded included the kerma-area product (KAP), the
      fluoroscopy time and the number of frames for each procedure: third quartiles
      from the total dosimetric databank were calculated and proposed as provisional
      local DRL. Since the complexity of a procedure must be taken into account when
      evaluating the radiation dose, in the case of embolisation of aneurysms (intra
      cranial), in this initial phase we assessed whether the complexity of the
      embolisation procedure is related to the size of the aneurysm and/or its site.
      We, therefore, re-calculated the DRL for only intra-cranial aneurysms, leaving
      aside the arteriovenous malformations. Considering that the DRL calculated for
      all the therapeutic procedures are similar to those calculated considering only
      intra-cranial aneurysms, at the moment we propose, besides the DRL for cerebral
      angiography, a single DRL for all interventional procedures, even when the
      clinical pictures are very different. Local preliminary DRLs were proposed as
      follows: 180 Gy cm(2), 12 min and 317 frames for cerebral angiography and 487 Gy
      cm(2), 46 min and 717 frames for interventional procedures (intra-cranial
      aneurysms and arteriovenous malformations).

PMID- 21074470
TI  - [Analysis of errors in manual versus electronic prescriptions in trauma
      patients].
AB  - OBJECTIVE: To detect, quantify, and compare the medication error produced with
      manual versus electronically assisted prescription systems. METHODS: A
      descriptive, observational, prospective study in two traumatology hospitalisation
      units; one with manual prescriptions and the other with electronically assisted
      prescriptions. Prescription errors were determined. RESULTS: We analysed 1,536
      lines of treatment (393 treatment forms) from 164 patients. With manual
      prescriptions, we detected errors in 19.54% of cases, compared to 9.4% in
      electronically assisted prescriptions. Omission errors were significantly lower
      with electronically assisted prescriptions, especially with drugs that act upon
      the central nervous system. CONCLUSIONS: Prescription error has decreased by 53%
      since computerising the prescription process. This is particularly useful for
      omission errors, as prescription is more complete. The decrease in error
      regarding drugs that act on the central nervous system stands out.

PMID- 21074471
TI  - Does rituximab increase the incidence of infectious complications? A narrative
      review.
AB  - BACKGROUND: Rituximab has increasingly been used for the treatment of
      hematological malignancies and autoimmune diseases, and its efficacy and safety
      are well established. Although clinical trials have shown conflicting results
      regarding the association of rituximab with infections, an increased incidence of
      infections has recently been reported in patients with lymphomas being treated
      with rituximab. However, clinical experience regarding the association of
      rituximab with different types of infection is lacking and this association has
      not been established in patients with rheumatoid arthritis. METHODS: All previous
      studies included in our literature review were found using a PubMed, EMBASE, and
      Cochrane database search of the English-language medical literature applying the
      terms 'rituximab', 'monoclonal antibodies', 'infections', 'infectious
      complications', and combinations of these terms. In addition, the references
      cited in these articles were examined to identify additional reports. RESULTS: We
      performed separate analyses of data regarding the association of rituximab with
      infection in (1) patients with hematological malignancies, (2) patients with
      autoimmune disorders, and (3) transplant patients. Recent data show that
      rituximab maintenance therapy significantly increases the risk of both infection
      and neutropenia in patients with lymphoma or other hematological malignancies. On
      the other hand, data available to date do not indicate an increased risk of
      infections when using rituximab compared with concurrent control treatments in
      patients with rheumatoid arthritis. However, there is a lack of sufficient long
      term data to allow such a statement to be definitively made, and caution
      regarding infections should continue to be exercised, especially in patients who
      have received repeated courses of rituximab, are receiving other
      immunosuppressants concurrently, and in those whose immunoglobulin levels have
      fallen below the normal range. Few data are available concerning the risk of
      organ transplant recipients developing infections following rituximab therapy.
      Data from case reports, case series, and retrospective studies correlate
      rituximab use with the development of a variety of infections in transplant
      patients. CONCLUSIONS: Further studies are needed to clarify the association of
      rituximab with infection. Physicians and patients should be educated about the
      association of rituximab with infectious complications. Monitoring of absolute
      neutrophil count and immunoglobulin levels and the identification of high-risk
      groups for the development of infectious complications, with timely vaccination
      of these groups, are clearly needed.

PMID- 21074472
TI  - O-GlcNAc modification, insulin signaling and diabetic complications.
AB  - O-GlcNAc glycosylation (O-GlcNAcylation) corresponds to the addition of N
      acetylglucosamine on serine and threonine residues of cytosolic and nuclear
      proteins. O-GlcNAcylation is a dynamic post-translational modification, analogous
      to phosphorylation, that regulates the stability, the activity or the subcellular
      localisation of target proteins. This reversible modification depends on the
      availability of glucose and therefore constitutes a powerful mechanism by which
      cellular activities are regulated according to the nutritional environment of the
      cell. O-GlcNAcylation has been implicated in important human pathologies
      including Alzheimer disease and type-2 diabetes. Only two enzymes, OGT and O
      GlcNAcase, control the O-GlcNAc level on proteins. Therefore, O-GlcNAcylations
      cannot organize in signaling cascades as observed for phosphorylations. O
      GlcNAcylations should rather be considered as a "rheostat" that controls the
      intensity of the signals traveling through different pathways according to the
      nutritional status of the cell. Thus, OGT attenuates insulin signal by O
      GlcNAcylation of proteins involved in proximal and distal steps in the PI-3
      kinase signaling pathway. This negative feedback may be exacerbated when cells
      are chronically exposed to elevated glucose concentrations and could thereby
      contribute to alterations in insulin signaling observed in diabetic patients. O
      GlcNAcylation also appears to contribute to the deleterious effects of
      hyperglycaemia on excessive glucose production by the liver and deterioration of
      beta-cell pancreatic function, resulting in worsening of hyperglycaemia
      (glucotoxicity). Moreover, O-GlcNAcylations directly participate in several
      diabetic complications. O-GlcNAcylation of eNOS in endothelial cells have been
      involved in micro- and macrovascular complications. In addition, O-GlcNAcylations
      activate the expression of profibrotic and antifibrinolytic factors, contributing
      to vascular and renal dysfunctions.

PMID- 21074473
TI  - An unusual morphological variant of the extensor digitorum brevis manus in an
      Indian male cadaver.
AB  - The extensor digitorum brevis manus is a supernumerary muscle of the dorsum of
      hand and is a relatively rare finding during dissection. Only 2-3% of the cases
      are found world wide. Here we report the case of extensor digitorum brevis manus
      in an approximately 65-year-old Indian male cadaver. This report discusses the
      variant anatomy, morphology, review of literature and clinical implications of
      this muscle. We believe that it is of importance to report the observation of
      this muscle as the variation reported herein should be of interest to clinicians,
      surgeons and anatomists for academic purposes.

PMID- 21074474
TI  - Current data on familial Mediterranean fever.

PMID- 21074475
TI  - [Autologous fat grafting in the treatment of lateral epicondylitis: preliminary
      results].
AB  - OBJECTIVES: The purpose of the study was to report our preliminary results of
      autologous fat grafting at the epicondyle level as a treatment for lateral
      epicondylitis. PATIENTS AND METHODS: Between 2008 and 2009, we used the technique
      of fat injection described by Coleman to treat with lateral epicondylitis, eight
      patients who were in failure of medical management. Effectiveness of this method
      was appreciated by patients satisfaction, pain improvement during daily
      activities. RESULTS: Sixty-two percent of patients noticed pain improvement. All
      patients were reviewed at a mean follow-up of nine months. CONCLUSIONS:
      Autologous fat grafting is a new interesting technique because it is safe. But,
      because of the small sample size, we are not able to conclude to its efficiency
      and to compare it to the other common techniques of management.

PMID- 21074476
TI  - [Results of transosseous reattachment for distal rupture of the biceps tendon.
      Evaluation of results].
AB  - Avulsion of the distal biceps brachii tendon is an uncommon injury. This is a
      retrospective review of cases operated in our department by transosseous suture
      fixation on the radial tuberosity, using the single anterior incision. Between
      2000 and 2007, a total of 10 patients with distal biceps tendon injury were
      included. All were men, with an average age of 39 years. The most common
      mechanism was passive extension against active flexion. The dominant limb was
      affected in all patients. Clinical diagnosis was the rule. Surgical reattachment
      to the radial tuberosity through the anterior approach to the elbow was
      performed. The preoperative period was one week in three cases, between one and
      three weeks in five cases, and superior to three weeks in two cases. Clinical and
      instrumental evaluation of the results was done. Average follow-up was 48 months.
      Subjective results were good in seven cases, acceptable in two cases and poor in
      one case. Nine patients return to their previous level activity with no
      limitations. The average range of motion was 0 degrees  of extension to 135
      degrees  of flexion. Strength testing of the injured limbs, compared to the
      contralateral, using the criteria described by Baker and Bierwagen, revealed a
      loss of 22% of supination strength and 32% of supination endurance. There was a
      loss of 14% of flexion strength and 27% of flexion endurance. There were two
      cases of superficial surgical site infection. There were no cases of nerve damage
      or heterotopic bone formation. Two main factors were found to explain the poor
      outcomes: experience of the surgeon and a long preoperative delay. Despite the
      limitations of this study, we found that transosseous reattachment of the biceps'
      distal tendon to the radial tuberosity can restore supination. Strength and
      endurance for supination can be better restored by early intervention.
      Complications are easily avoided if surgery is performed early and by experts.

PMID- 21074477
TI  - The air-liquid flow in a microfluidic airway tree.
AB  - Microfluidic techniques are employed to investigate air-liquid flows in the lung.
      A network of microchannels with five generations is made and used as a simplified
      model of a section of the pulmonary airway tree. Liquid plugs are injected into
      the network and pushed by a flow of air; they divide at every bifurcation until
      they reach the exits of the network. A resistance, associated with the presence
      of one plug in a given generation, is defined to establish a linear relation
      between the driving pressure and the total flow rate in the network. Based on
      this resistance, good predictions are obtained for the flow of two successive
      plugs in different generations. The total flow rate of a two-plug flow is found
      to depend not only on the driving pressure and lengths of the plugs, but also the
      initial distance between them. Furthermore, long range interactions between
      daughters of a dividing plug are observed and discussed, particularly when the
      plugs are flowing through the bifurcations. These interactions lead to different
      flow patterns for different forcing conditions: the flow develops symmetrically
      when subjected to constant pressure or high flow rate forcing, while a low flow
      rate driving yields an asymmetric flow.

PMID- 21074479
TI  - Uneven access to safe drinking water for First Nations in Canada: connecting
      health and place through source water protection.
AB  - Source water protection has gained considerable attention in the water resources
      literature particularly after several well publicized (non-First Nations) water
      contamination events in Canada. This short report explores health and place
      through an examination of access to safe drinking water in a developed country.
      For First Nations in Canada, safe drinking water remains a serious, albeit under
      reported, problem. The incidence of contaminated drinking water is pervasive in
      many First Nations communities. Attempts to "fix" water quality problems using
      technology alone have produced only limited success. It will be shown that
      greater attention to source water protection has potential for both to improve
      drinking water quality as well as to re-connect health and place for First
      Nations in Canada.

PMID- 21074478
TI  - Dyskinesias do not develop after chronic intermittent levodopa therapy in
      clinically hemiparkinsonian rhesus monkeys.
AB  - The stable 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      hemiparkinsonian (HP) rhesus monkey model of Parkinson's disease (PD) has been
      frequently used to test preclinical experimental therapeutics targeted to treat
      patients with advanced PD who suffer from motor fluctuations and drug-induced
      dyskinesias. We retrospectively analyzed data from 17 stable HP rhesus monkeys
      treated long-term with chronic intermittent dosing of levodopa (LD) in an attempt
      to induce choreoathetoid and dystonic dyskinesias. Rhesus monkeys in stable HP
      state for greater than 6 months as confirmed by multiple blinded behavioral
      ratings and (18)F-dopa Positron Emission Tomography (PET) were treated with
      optimal doses of LD to provide maximal amelioration of unilateral clinical
      parkinsonism without any adverse effects. Thereafter, each animal was given
      chronic intermittent daily challenge with doses of LD up to 700 mg/day orally or
      with 300 mg/kg/day parenteral injections. LD treatments failed to induce
      choreoathetoid and dystonic dyskinesias in these animals despite chronic
      intermittent high dose administration. These results suggest that the stable
      strictly unilateral HP rhesus monkey model of PD may not be a suitable animal
      model to test experimental therapeutics targeted against dyskinesias, and that
      bilateral parkinsonian rhesus models that readily demonstrate drug-induced
      dyskinesias and clinically relevant motor fluctuations are more appropriate for
      preclinical experimental testing of therapies designed to treat patients with
      advanced PD.

PMID- 21074480
TI  - Interpreting research on clinical prediction rules for physiotherapy treatments.

PMID- 21074481
TI  - Role of IL-15 in immune-mediated and infectious diseases.
AB  - IL-15 has a broad spectrum of biological activities. It is crucial for the
      development, proliferation, survival and differentiation of multiple cells from
      both innate and adaptive immune systems. However, IL-15 up-regulation has a
      central role in the development of several autoimmune or chronic inflammatory
      disorders. Therefore, targeting IL-15 or its receptor may have a valuable impact
      on the treatment of immune-mediated diseases. On the other hand, in some
      infectious diseases, IL-15 production is compromised but IL-15 given exogenously
      can potentially enhance immune responses to pathogens. Here, we discuss the
      current understanding of IL-15 role in immune-mediated and infectious diseases as
      well as its therapeutic use.

PMID- 21074483
TI  - Retention of conditioning agent hyaluronan on hydrogel contact lenses.
AB  - Hyaluronan, a member of the glycosaminoglycan family of biological
      polysaccharides, is a high-molecular-weight disaccharide polymer found throughout
      the human body, particularly in the eye. Bausch+Lomb BiotrueTM multi-purpose
      solution contains hyaluronan as a lens conditioning agent. The retention of
      hyaluronan from Biotrue multi-purpose solution to a variety of hydrogel contact
      lenses was evaluated over time. Fluorescein-tagged hyaluronan was allowed to
      adhere to lenses, which were then rinsed with balanced salt solution at a rate
      comparable to human tear secretion. Results demonstrated that hyaluronan was
      released slowly throughout the rinse period. The chemistry of the lens materials
      appeared to contribute to the hyaluronan retention capacity for each lens type.
      The results suggest that a multi-purpose solution containing hyaluronan has the
      potential to provide lens conditioning regardless of the hydrogel contact lens
      used.

PMID- 21074484
TI  - Growth and development: prokaryotes.

PMID- 21074485
TI  - Synthesis, characterization and photoluminescence properties of CaSiO3:Eu3+ red
      phosphor.
AB  - CaSiO3:Eu3+ (1-5 mol%) red emitting phosphors have been synthesized by a low
      temperature solution combustion method. The phosphors have been well
      characterized by powder X-ray diffraction (PXRD), Fourier transform infrared
      spectroscopy (FTIR), scanning electron microscopy (SEM) and optical spectroscopy.
      PXRD patterns reveal monoclinic CaSiO3 phase can be obtained at 900 degrees C.
      The SEM micrographs show the crystallites with irregular shape, mostly angular.
      Upon 254 nm excitation, the phosphor show characteristic fluorescence 5D0->7FJ
      (J=0, 1, 2, 3, 4) of the Eu3+ ions. The electronic transition located at 614 nm
      corresponding to 5D0->7F2 of Eu3+ ions, which is stronger than the magnetic
      dipole transition located at 593 nm corresponding to 5D0->7F1 of Eu3+ ions.
      Different pathways involved in emission process have been studied. Concentration
      quenching has been observed for Eu3+ concentration>4 mol%. UV-visible absorption
      shows an intense band at 240 nm in undoped and 270 nm in Eu3+ doped CaSiO3 which
      is attributed to oxygen to silicon (O-Si) ligand-to-metal charge-transfer (LMCT)
      band in the SiO3(2-) group. The optical energy band gap is widened with increase
      of Eu3+ ion dopant.

PMID- 21074482
TI  - IL-17 family member cytokines: regulation and function in innate immunity.
AB  - Recently, the IL-17 family member cytokines have become prominent subjects of
      investigation. IL-17 (IL-17A) is the best-described member of this family where
      its production has been mainly attributed to a specialized T helper subset of the
      adaptive immune response termed Th17. However, recent research on this and other
      Th17 cytokines has revealed new sources and functions of IL-17 family members in
      the innate immune response. This review will highlight recent advances in the
      field of IL-17 family member cytokines and will predominantly focus on the innate
      regulation and function of IL-17, IL-17F, and IL-25.

PMID- 21074486
TI  - The synthesis and spectral properties of a stimuli-responsive D-pi-A charge
      transfer dye.
AB  - A new donor-pi-acceptor (D-pi-A) type isophorone dye was synthesized by the
      condensation reaction between 2-(3,5,5-trimethylcyclohex-2-enylidene)
      malononitrile and indole-3-carboxaldehyde. The chemical structure of the dye was
      characterized by 1H NMR, EA and MS. A novel, chromogenic, fluorescent dye based
      on indol as donor unit and isophorone as acceptor unit displayed marked UV
      visible absorption changes and highly selective fluorescence quenching in the
      presence of fluoride ion. The dye also exhibited sizeable colour changes when
      used as a pH-induced molecular switch and as a detector for volatile organic
      compounds. The absorption and fluorescent intensity of the dye can be reversibly
      selected by protonation/deprotonation of the amine moiety via control of
      intramolecular charge transfer (ICT), leading to a molecular switch with "on" and
      "off" states.

PMID- 21074487
TI  - Synthesis, spectral, thermal and antimicrobial studies of some new tri metallic
      biologically active ceftriaxone complexes.
AB  - Iron, cobalt, nickel and copper complexes of ceftriaxone were prepared in 1:3
      ligand:metal ratio to examine the ligating properties of the different moieties
      of the drug. The complexes were found to have high percentages of coordinated
      water molecules. The modes of bonding were discussed depending on the infrared
      spectral absorption peaks of the different allowed vibrations. The Nujol mull
      electronic absorption spectra and the magnetic moment values indicated the Oh
      geometry of the metal ions in the complexes. The ESR spectra of the iron, cobalt,
      and copper complexes were determined and discussed. The thermal behaviors of the
      complexes were studied by TG and DTA techniques. The antimicrobial activities of
      the complexes were examined and compared to that of the ceftriaxone itself.

PMID- 21074488
TI  - ESR and optical studies of Cu2+ doped zinc glutamate dihydrate.
AB  - The ESR study of the Cu2+ doped zinc glutamate dihydrate is carried out at room
      temperature. Two magnetically nonequivalent sites for Cu2+ are observed. The spin
      Hamiltonian parameters are determined with the fitting of spectra to rhombic
      symmetry crystalline field. The parameters are as follows: Cu2+(I): gx=2.0170+/
      0.0002, gy=2.0768+/-0.0002, gz=2.2334+/-0.0002, Ax=(74+/-2)*10(-4), Ay=(99+/
      2)*10(-4), Az=(134+/-2)*10(-4) cm(-1)and Cu2+(II): gx=2.0180+/-0.0002,
      gy=2.0550+/-0.0002, gz=2.1633+/-0.0002, Ax=(100+/-2)*10(-4), Ay=(100+/-2)*10(-4),
      Az=(115+/-2)*10(-4) cm(-1). The ground state wave function is also determined.
      The g-anisotropy is evaluated and compared with the experimental value. Using the
      data of optical absorption study undertaken at room temperature the nature of
      bonding in the complex is also discussed.

PMID- 21074489
TI  - Fatal disseminated adenovirus infection in a young adult with systemic lupus
      erythematosus.
AB  - BACKGROUND: The use of corticosteroids and other immunosuppressive agents
      increases the risk of infection in patients with systemic lupus erythematosus
      (SLE). The role of human adenoviruses (HAdV) in the etiology of acute viral
      diseases in these patients is not known. OBJECTIVES: Describe a case of acute
      fatal disseminated adenovirus infection in an SLE patient receiving
      immunosuppressive therapy. STUDY DESIGN: Case report and detailed viral diagnosis
      by real time PCR and molecular typing of virus isolates by sequencing of hexon
      and fiber genes and restriction enzyme analysis of viral DNA. RESULTS: HAdV was
      detected by real time PCR in multiple clinical specimens including respiratory,
      urine, plasma, synovial fluid, and cerebrospinal fluid. Amplification and
      sequence analysis of the hexon and fiber genes identified the virus as HAdV-7
      like for both coding regions. Adenoviruses isolated from respiratory and urine
      specimens were identical and corresponded to genome type 7d2 by restriction
      enzyme analysis of viral DNA. The isolated strain encodes a unique fiber gene
      with a 6-nucleotide deletion corresponding to amino acid positions 250 and 251 in
      the knob region and not previously described for closely related genomic variants
      of HAdV-7. CONCLUSIONS: Adenovirus detection should be included in the diagnostic
      testing to determine the infectious etiology of fever and/or respiratory symptoms
      in SLE patients.

PMID- 21074491
TI  - A hospital based study on inter- and intragenotypic diversity of human rotavirus
      A VP4 and VP7 gene segments, Germany.
AB  - BACKGROUND: Efforts to reduce the impact of group A rotaviruses on human
      morbidity and mortality rely on oral immunisation with live attenuated or
      recombinant vaccines. A major challenge in immunisation is the vast inter- and
      intragenotypic diversity accomplished by circulating rotaviruses. OBJECTIVES: To
      monitor rotavirus inter- and intragenotypic diversity in hospitalised children.
      STUDY DESIGN: From January 2008 to December 2009 stool samples from 1994
      paediatric in-patients suffering from diarrhoea were screened for rotavirus.
      Rotavirus G- and P-genotypes were determined by nucleotide sequencing and
      phylogenetic analysis was performed. RESULTS: Rotavirus A was detected in stool
      samples of 341 children, comprising G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], as
      well as uncommon G12P[6] genotypes and mixed infections. Predominant strains
      shifted from G1P[8] and G9P[8] genotypes in the first season to G3P[8] and G4P[8]
      genotypes in the second season. The highest intragenotypic diversity was detected
      in G1 strains and consisted of co-circulating G1-Ic, G1-Id, G1-Ie and G1-II
      rotaviruses. The G2 analysis revealed different intragenotypic lineages: G2-IIa,
      G2-IIb and G2-IIc. Interestingly, the circulating G4-Ib rotaviruses were
      characterised by insertions of 3 or 6 additional coding nucleotides within
      variable region 4 of VP7. Whereas different G9-III VP7 gene segments were
      detected G3-Ia sequences were highly homologous. In the VP4 analysis P[8]-III
      gene segment predominated over P[4]-Vb, P[8]-I, P[8]-IV and P[6]-I. CONCLUSIONS:
      A remarkable rotavirus heterogeneity was detected in the limited local setting
      and time span. Continued monitoring and nucleotide sequencing is necessary to
      document possible effects of rising immunisation levels on intragenotypic
      rotavirus diversity.

PMID- 21074490
TI  - Resistance and virulence mutations in patients with persistent infection by
      pandemic 2009 A/H1N1 influenza.
AB  - BACKGROUND: Pandemic 2009 influenza A/H1N1 (H1N1v) is resistant to adamantanes,
      leaving neuraminidase inhibitors as the only therapeutic option. Other mutations
      are considered to be associated with virulence and clinical severity. However,
      out of the surveillance programs, few studies analyze the presence of
      resistance/virulent H1N1v variants in certain clinical circumstances. OBJECTIVES:
      To define the frequency and role of resistance and virulence mutations in a
      specific clinical circumstance-in patients with persistent infection by H1N1v.
      STUDY DESIGN: Observational study of patients with persistent H1N1v infection
      admitted to our hospital. RESULTS: NAI-resistance mutations were detected in
      14.3% of cases with persistent infection (2/14), and in none of the non
      persistent controls (0/15). These cases were initially infected with susceptible
      variants that acquired resistance at different time-points after therapy with
      oseltamivir (OTV). The first case (case 2) was an HIV-positive patient who
      rapidly acquired resistance 9 days after diagnosis (6 days on OTV) and whose
      infection resolved after standard OTV therapy. The second case (case 3) was a
      patient with chronic lymphocytic leukemia [corrected] and the longest viral
      persistence (59 days). The resistance mutation was detected in the specimen taken
      on day 37 after diagnosis (30 days on OTV). Once the resistance mutation was
      identified, OTV was substituted by zanamivir and the infection resolved. In
      addition to mutations encoding resistance, variants associated with virulence
      were also sought. The D225G mutation was not found in any case, whereas the D225E
      variant was identified in three persistent cases but also in two non-persistent
      ones. In one patient, the D225E substitution coincided with the H275 resistant
      mutation. CONCLUSIONS: NAI-resistance mutations were detected, at rather
      different paces, in non-severe immunosuppressed cases with persistent infection
      by influenza A/H1N1v.

PMID- 21074492
TI  - Transcranial direct current stimulation over the motor association cortex induces
      plastic changes in ipsilateral primary motor and somatosensory cortices.
AB  - OBJECTIVE: This study was performed to elucidate whether transcranial direct
      current stimulation (tDCS) over the motor association cortex modifies the
      excitability of primary motor (M1) and somatosensory (S1) cortices via neuronal
      connectivity. METHODS: Anodal, cathodal, and sham tDCS (1 mA) over the left motor
      association cortex was applied to 10 subjects for 15 min using electrodes of two
      sizes (9 and 18 cm(2)). Both motor evoked potentials (MEPs) and somatosensory
      evoked potentials (SEPs) were recorded before, immediately after, and 15 min
      after tDCS. Electrode positions were confirmed by overlaying them on MRI
      anatomical surface images of two individuals. RESULTS: After applying anodal tDCS
      using the large electrode, amplitudes of MEP components significantly decreased,
      whereas those of early SEP components (N20 and P25) increase. Opposite effects
      were observed on MEPs and SEPs after cathodal tDCS. However, a small electrode
      did not significantly influence either MEPs or SEPs, irrespective of polarity.
      The small electrode covered mainly the dorsal premotor cortex (PMd) while the
      large electrode involved the supplementary motor area (SMA) in addition to PMd.
      CONCLUSIONS: These results suggest that anodal tDCS over PMd together with SMA
      enhanced the inhibitory input to M1 and excitatory input to S1, and that cathodal
      tDCS might lead to an opposite effect. SIGNIFICANCE: The finding that only the
      large electrode modulated M1 and S1 implies that activation of PMd together with
      SMA by tDCS can induce plastic changes in primary sensorimotor areas.

PMID- 21074493
TI  - Assessment of electroencephalographic functional connectivity in term and preterm
      neonates.
AB  - OBJECTIVE: To study how functional connectivity of neonate EEG during sleep is
      assessed by different interdependence indices and to analyze its dependence on
      conceptional (CA), gestational (GA) and/or chronological age (CRA). METHODS: EEG
      data from eight cortical regions were recorded during active (AS) and quiet sleep
      (QS) in three groups of seven neonates each: preterm (PT; GA: 33-34 weeks; CA: 39
      40 weeks), junior-term (JT; GA: 38-39 weeks; CA: 39-40 weeks) and senior-term
      neonates (ST; GA: 38-39 weeks; CA: 44-45 weeks). EEG functional connectivity was
      assessed by means of the coherence function (its magnitude (MSC) and its
      imaginary part (IMC)) and a measure of phase synchronization called phase lag
      index (PLI). RESULTS: Inter-hemispheric connectivity: (a) during AS in the beta
      band, the MSC of the ST group was greater than that of the PT group for the
      temporal region; (b) during QS in the delta band, both PLI and IMC of the ST
      group were different to those of the PT group for the frontopolar and central
      regions, whereas ST-JT differences were only found for PLI. Intra-hemispheric
      connectivity: (a) during AS in the beta band the MSC of the ST group was greater
      than that of the PT group for the left frontopolar-centrotemporal and right
      occipital-centrotemporal regions; (b) during QS in the beta band, both IMC and
      PLI were different for the JT group than for the PT and the ST groups for the
      right and left occipital-centrotemporal regions. CONCLUSIONS: EEG inter- and
      intra-hemispheric functional connectivity in neonates during sleep changes with
      the CA and CRA in delta and beta bands. SIGNIFICANCE: The neonate's brain
      development during the first weeks of life can be traced from changes in the
      characteristics of EEG functional connectivity.

PMID- 21074495
TI  - Epidemiology of bacteraemia in Hamad general hospital, Qatar: a one year hospital
      based study.
AB  - We conducted a one-year observational study from July 2007 to June 2008 to
      describe the epidemiology of bacteraemia at Hamad general hospital. During this
      period, a total of 452 episodes of bacteraemia occurred, which corresponds to a
      rate of 19/1000 hospital admissions. Most patients 58.8% (266/452) had community
      acquired bacteraemia, and primary bacteraemia accounted for 62.2% (281/452) of
      the cases. The most common source of bacteraemia was intravenous catheterization
      in 19.2% (87/452) but no source was identified in 42.9% (194/452) of the
      episodes. Gram-negative organisms were isolated in 63.1% (285/452) episodes with
      Escherichia coli being the most frequent 21.5% (97/452). Multidrug resistance was
      observed in 33.3% (7/21) of all Pseudomonas aeruginosa isolates, 50% (6/12) of
      Acinetobacter isolates and 28.6% (6/21) of Enterobacter isolates, whereas all
      ESBL producing Klebsiella spp. and E. coli were multiresistant. The percentages
      of oxacillin resistant coagulase negative Staphylococci isolates and methicillin
      resistant Staphylococcus aureus isolates were 81.8% (27/33) and 13.2% (7/53)
      respectively. In hospital mortality was 22.5% (102/452), and inadequate treatment
      and septic shock were found to be independent predictors of mortality. Therefore,
      bloodstream infection surveillance is crucial to produce meaningful guidelines
      for prevention (e.g., catheter-related) and empirical treatment of bacteraemia in
      Qatar.

PMID- 21074494
TI  - Inorganic nanoparticle-based contrast agents for molecular imaging.
AB  - Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron
      oxide NPs and gold NPs have been developed as contrast agents for diagnostics by
      molecular imaging. Compared with traditional contrast agents, NPs offer several
      advantages: their optical and magnetic properties can be tailored by engineering
      the composition, structure, size and shape; their surfaces can be modified with
      ligands to target specific biomarkers of disease; the contrast enhancement
      provided can be equivalent to millions of molecular counterparts; and they can be
      integrated with a combination of different functions for multimodal imaging.
      Here, we review recent advances in the development of contrast agents based on
      inorganic NPs for molecular imaging, and also touch on contrast enhancement,
      surface modification, tissue targeting, clearance and toxicity. As research
      efforts intensify, contrast agents based on inorganic NPs that are highly
      sensitive, target-specific and safe to use are expected to enter clinical
      applications in the near future.

PMID- 21074496
TI  - Pediatric travelers visiting friends and relatives (VFR) abroad: illnesses,
      barriers and pre-travel recommendations.
AB  - Global mobility has shown a steady rise in recent years, with increased
      immigration and international travel. The VFR traveler is a traveler whose
      primary purpose of travel is to visit friends and relatives (VFR), where there is
      a gradient of risk between home and destination. Children are more likely to be
      VFR travelers than adults. Pediatric VFR travelers have higher risks for certain
      infectious travel-related illnesses and face multiple barriers in receiving
      comprehensive pre-travel care. This review focuses on the current state of
      knowledge of the pediatric VFR traveler, including epidemiological risks,
      barriers to adequate pre-travel services, and specific recommendations for
      disease prevention.

PMID- 21074497
TI  - Removal of the retained cervical stump after supracervical hysterectomy.
AB  - Current studies do not support any benefit of supracervical hysterectomy in
      reducing perioperative morbidity and adverse effects on pelvic support, sexual
      and urinary function. Prolapse, pelvic mass and bleeding were the most common
      indications for trachelectomy after supracervical hysterectomy. Vaginal
      trachelectomy was the preferred approach to the procedure involving the least
      complications.

PMID- 21074498
TI  - Optical coherence tomography in adult-onset vitelliform dystrophy.
AB  - BACKGROUND: Adult-onset vitelliform dystrophy (AOVD) is as a bilateral macular
      dystrophy that presents as a subretinal, oval, or round yellowish deposition in
      the macula. The lesions may be elevated and measure approximately 1/3 to 1 disc
      diameter (DD) in size. The dystrophy usually manifests between 30 and 50 years of
      age and has been genetically linked. Features of AOVD have been evaluated by
      optical coherence tomography (OCT). OCT examination shows subfoveal
      hyperreflective lesions lying on the retinal pigment epithelium (RPE) with slight
      separation between the RPE and photoreceptor layers. OCT is a diagnostic tool
      that provides insight into the morphologic characteristics of AOVD. CASE REPORT:
      A 67-year-old black woman presented with complaints of decreased vision and
      metamorphopsia in her right eye of 1 year's duration. The patient's ocular
      history was positive for "macular degeneration" for which she was given eye
      vitamins. The patient's best-corrected visual acuities were 20/30 in the right
      eye and 20/20 in the left eye. Fundus examination found bilateral, subfoveal
      lesions. Optical coherence tomography demonstrated an elevated, well
      circumscribed area of hyperreflectivity within the RPE in each eye. This
      description is that of a pattern-dystrophy of the RPE, namely, adult-onset
      vitelliform dystrophy. CONCLUSION: OCT is a noninvasive instrument that provides
      information on the morphology of AOVD. It not only isolates the location of the
      lesion but can be utilized to monitor the stability of the condition. OCT
      interpretation of macular lesions can aid in diagnosis and management.

PMID- 21074500
TI  - Advances in perfusion magnetic resonance imaging in Alzheimer's disease.
AB  - Recent research has demonstrated that brain circulation abnormalities, either
      during task-induced neural activity or at rest, are more commonly associated with
      Alzheimer's disease (AD) than was previously thought. This is consistent with the
      increasing attention to the early involvement of vascular risk factors in the
      development of AD, in addition to the dominating neurodegenerative pathology.
      Early detection of cerebral perfusion changes could help advance diagnosis and
      intervention therapies. The present article reviews advances in perfusion
      magnetic resonance imaging in the study of AD. In general, there are consistent
      accounts of cerebral hypoperfusion in the temporal and parietal lobes in people
      with clinically diagnosed AD. In the early stages of the disease, transient
      hyperperfusion may occur particularly in the prefrontal cortex, possibly as a
      compensatory effect. Nevertheless, significant variability in the details of
      perfusion patterns is present in the early phases, making the use of these
      methods in early diagnosis difficult. Noninvasive perfusion-weighted magnetic
      resonance imaging methods have advantages over nuclear medicine imaging,
      especially for safe usage in long-term follow-up studies. Optimization of
      perfusion-weighted imaging techniques is crucial for any future clinical
      application. Additional studies are needed with optimization likely to come with
      3T and higher field strength magnets.

PMID- 21074499
TI  - Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1
      signaling.
AB  - The JAK2V617F mutation is associated with distinct myeloproliferative neoplasms,
      including polycythemia vera (PV) and essential thrombocythemia (ET), but it
      remains unclear how it generates disparate disorders. By comparing clonally
      derived mutant and wild-type cells from individual patients, we demonstrate that
      the transcriptional consequences of JAK2V617F are subtle, and that JAK2V617F
      heterozygous erythroid cells from ET and PV patients exhibit differential
      interferon signaling and STAT1 phosphorylation. Increased STAT1 activity in
      normal CD34-positive progenitors produces an ET-like phenotype, whereas
      downregulation of STAT1 activity in JAK2V617F-heterozygous ET progenitors
      produces a PV-like phenotype. Our results illustrate the power of clonal
      analysis, indicate that the consequences of JAK2V617F reflect a balance between
      STAT5 and STAT1 activation and are relevant for other neoplasms associated with
      signaling pathway mutations.

PMID- 21074501
TI  - DNA replication initiation as a key element in thymineless death.
AB  - Thymine deprivation results in the loss of viability in cells from bacteria to
      eukaryotes. Numerous studies have identified a variety of molecular processes and
      cellular responses associated with thymineless death (TLD). It has been observed
      that TLD occurs in actively growing cells, and DNA damage and DNA recombination
      structures have been associated with cells undergoing TLD. We measured the loss
      of viability in thymine-starved cells differing in the number of overlapping
      replication cycles (n), and we found that the magnitude of TLD correlates with
      the number of replication forks. By using pulsed field gel electrophoresis
      (PFGE), we determined the proportion of linear DNA (DSBs) and the amount of DNA
      remaining in the well after treatment with XbaI (nmDNA) under thymine starvation
      in the absence or presence of both rifampicin (suppressing TLD) and hydroxyurea
      (maintaining TLD). Our results indicate that DSBs and nmDNA are induced by
      thymine starvation, but they do not correlate with the lethality observed in the
      presence of the drugs. We asked whether TLD was related to chromosomal DNA
      initiation. DNA labeling experiments and flow cytometric analyses showed that new
      initiation events were induced under thymine starvation. These new DNA
      replication initiation events were inhibited in the presence of rifampicin but
      not in the presence of hydroxyurea, indicating that TLD correlates with the
      induction of new initiation events in Escherichia coli. In support of this
      finding, cells carrying a deletion of the datA site, in which DNA initiation is
      allowed in the presence of rifampicin, underwent TLD in the presence of
      rifampicin. We propose that thymineless-induced DNA initiation generates a
      fraction of DNA damage and/or nmDNA at origins that is critical for TLD. Our
      model provides new elements to be considered when testing mammalian
      chemotherapies that are based on the inhibition of thymidylate synthetase.

PMID- 21074502
TI  - Quantification of acetylcholine, choline, betaine, and dimethylglycine in human
      plasma and urine using stable-isotope dilution ultra performance liquid
      chromatography-tandem mass spectrometry.
AB  - Disorders in choline metabolism are related to disease conditions. We developed a
      stable-isotope dilution ultra performance liquid chromatography-mass spectrometry
      (UPLC-MS/MS) method for the simultaneous quantification of acetylcholine (ACh),
      betaine, choline, and dimethylglycine (DMG). We used this method to measure
      concentrations of the analytes in plasma and urine in addition to other
      biological fluids after a protein precipitation by acetonitrile. The detection
      limits were between 0.35 nmol/L (for ACh in urine) and 0.34 MUmol/L (for betaine
      in urine). ACh concentrations were not detectable in plasma. Intraassay and
      interassay coefficient of variation (CVs) were all <10.0% in biological fluids,
      except for DMG in cerebrospinal fluid (CV=12.44%). Mean recoveries in urine pool
      samples were between 99.2% and 103.9%. The urinary excretion of betaine, choline,
      and DMG was low, with approximately 50.0% higher excretion of choline in females
      compared to males. Median urinary excretion of ACh were 3.44 and 3.92 MUmol/mol
      creatinine in males and females, respectively (p=0.689). Plasma betaine
      concentrations correlated significantly with urinary excretions of betaine
      (r=0.495, p=0.027) and choline (r=0.502, p=0.024) in females. Plasma choline
      concentrations correlated significantly with urinary excretion of ACh in males
      (r=0.419, p=0.041) and females (r=0.621, p=0.003). The new method for the
      simultaneous determination of ACh, betaine, choline, and DMG is sensitive,
      precise, and fast enough to be used in clinical investigations related to the
      methylation pathway.

PMID- 21074503
TI  - Comparing parent and child perceptions of stigmatizing behavior experienced by
      children with burn scars.
AB  - This study examined perceptions of stigmatization in a sample of 85 pediatric
      burn survivors and their parents. Survivors and a parent independently completed
      the Perceived Stigmatization Questionnaire (PSQ) rating the frequency that the
      child experienced three types of stigmatizing behaviors: absence of friendly
      behavior, confused and staring behavior, and hostile behavior. The sample was
      divided into a high (top 25%) and low (bottom 75%) perceived stigmatization
      groups. The mean ratings of parents did not significantly differ from that of
      children reporting low stigmatization. The mean PSQ parent ratings were
      significantly lower than those of children reporting high stigmatization.
      Additionally, the concordance on PSQ subscale scores within child-parent dyads
      was significantly lower in children reporting high stigmatization relative to
      child-parent dyads of children reporting low stigmatization. Children surviving
      burns may experience stigmatization that is under-perceived by their parents.
      Clinicians should be alert to this potential discrepancy.

PMID- 21074504
TI  - Deltopectoral groove full-thickness skin graft donor site for head and neck skin
      cancer excisions.

PMID- 21074505
TI  - The "crossbeam technique": a technique for taking bone grafts from the ilium.

PMID- 21074506
TI  - Our strategy in complication management of augmentation mammaplasty with
      polyacrylamide hydrogel injection in 235 patients.
AB  - Polyacrylamide hydrogel (PAAG) was once widely used in breast augmentation in
      China. Although it had been banned for augmentation mammaplasty in 2006, a large
      number of patients whose breasts were augmented with the gel injection have
      continued to seek medical advice because of its complications. The clinical
      management of these complications has never been standardised. The data of a
      total of 235 patients with complications following PAAG-injected breast
      augmentation have been summarised and the types and causations analysed. Magnetic
      resonance imaging (MRI) was undertaken in 228 patients with palpable masses,
      breast pain or tenderness, asymmetry or deformity and functional or psychological
      problems to eliminate neoplasm, infection and to delineate the diseases. The
      surgical gel evacuation via periareolar incisions was performed for all patients
      and immediate silicone breast prostheses were implanted in 108 patients and were
      delayed in 28 cases by 6 months. Most patients (214/235) of the group were
      satisfied with the treatment, and symptoms disappeared after removal of the gel.
      The gel distribution and involved tissue were well defined and neoplasm was ruled
      out by MRI. Postoperative MRI in 68 patients revealed that no obvious PAAG
      remaining. In either immediate or delayed reconstructive patients with silicone
      breast implants, good breast contour presented. A diagnosis and management
      strategy for these complications is proposed. In conclusion, the breast masses,
      pain and deformity are major complications after PAAG-injected breast
      augmentation. Psychological problems should be paid attention to. MRI is a
      sensitive and accurate method for diagnosis and treatment evaluation. Surgical
      removal of injected gel is the preferred method for complication management. The
      implantation of silicone prostheses for breast contour restoration after PAAG
      evacuation is effective for patients under strict selection. Our strategy for
      treating PAAG-related complications proved useful.

PMID- 21074507
TI  - Inter-professional collaboration in delivery suite: a qualitative study.
AB  - BACKGROUND: Communication problems between clinicians are the most common cause
      of preventable adverse events in hospitals. In spite of these known risks the
      'turf wars' between midwives and doctors continue unabated. QUESTION: What
      factors affect inter-professional interactions in birthing units? PARTICIPANTS: 9
      doctors and 10 midwives from 10 Australian maternity units. METHODS: Interpretive
      Interactionism was the research design. Probing in-depth interviews were
      conducted to elicit stories of inter-professional interactions and their
      perceived effects on birthing outcomes. Analysis resulted in two theoretical
      models of inter-professional interaction: one positive and the other negative.
      FINDINGS: Midwives and doctors agree that positive interactions are
      collaborative, include the woman and her partner and are associated with the best
      possible outcomes and experiences possible. In contrast, they agree that negative
      interactions involve power struggles between the professionals and these are
      associated with adverse outcomes. All participants are able to demonstrate
      emotional and social competence when interacting and applied those skills
      sometimes. Factors related to the organisational culture within the 'birth
      territory' of a particular maternity unit seem to be predictive of the type of
      interactions that are likely to occur there. CONCLUSION: Interventions to enhance
      inter-professional collaboration should be directed first at changing
      organisational structures and policies to promote easy opportunities for natural
      dialogue between doctors and midwives.

PMID- 21074508
TI  - Home birth and the National Australian Maternity Services Review: too hot to
      handle?
AB  - BACKGROUND: In February 2009 the Improving Maternity Services in Australia - The
      Report of the Maternity Services Review (MSR) was released, with the personal
      stories of women making up 407 of the more than 900 submissions received. A
      significant proportion (53%) of the women were said to have had personal
      experience with homebirth. Little information is provided on what was said about
      homebirth in these submissions and the decision by the MSR not to include
      homebirth in the funding and insurance reforms being proposed is at odds with the
      apparent demand for this option of care. METHOD: Data for this study comprised
      832 submissions to the MSR that are publicly available on the Commonwealth of
      Australia Department of Health and Aging website. All 832 submissions were
      downloaded, coded and then entered into NVivo. Content analysis was used to
      analyse the data that related to homebirth. FINDINGS: 450 of the submissions were
      from consumers of maternity services (54%). Four hundred and seventy (60%) of the
      submissions mentioned homebirth. Overall there were 715 references to home birth
      in the submissions. The submissions mentioning homebirth most commonly discussed
      the 'Benefits' and 'Barriers' in accessing this option of care. Benefits to the
      baby, mother and family were described, along with the benefits obtained from
      having a midwife at the birth, receiving continuity of care and having a good
      birth experience. Barriers were described as not having access to a midwife, no
      funding, no insurance and lack of clinical privileging for midwives. CONCLUSION:
      Many positive recommendations have come from the MSR, however the decision to
      exclude homebirth from these reforms is perplexing considering the large number
      of submissions describing the benefits of and barriers to homebirth in Australia.
      A concerning number of submissions discuss having had or having considered an
      unattended birth at home due to these barriers. Overall there is the belief that
      not enabling access to funded, insured homebirth in Australia is a violation of
      human rights. It appears that homebirth was considered by the MSR as 'too hot to
      handle' and by dismissing it as a minority issue the government sought to avoided
      dealing with homebirth as a 'sensitive and controversial issue.'

PMID- 21074509
TI  - A curious combination...

PMID- 21074510
TI  - Advantages of isothermal titration calorimetry for xylanase kinetics in
      comparison to chemical-reducing-end assays.
AB  - In lignocellulosic raw materials for biomass conversion, hemicelluloses
      constitute a substantial fraction, with xylan being the primary part. Although
      many pretreatments reduce the amount or change the distribution of xylan, it is
      important to degrade residual xylan so as to improve the overall yield.
      Typically, xylanase reaction rates are measured in stopped assays by chemical
      quantification of the reducing ends. With isothermal titration calorimetry (ITC),
      the heat flow of the hydrolysis can be measured in continuous fashion, with the
      reaction rate being directly proportional to the heat flow. Reaction enthalpies
      for carbohydrate hydrolysis are typically below 5kJ/mol, which is the limiting
      factor for straight forward calorimetric quantification of enzymatic reaction
      rates using current ITC technology. To increase the apparent reaction enthalpy,
      we employed a subsequent oxidation of hydrolysis products by carbohydrate oxidase
      and catalase. Here we show that the coupled assay with carbohydrate oxidase and
      catalase can be used to measure enzyme kinetics of a GH10 xylanase from
      Aspergillus aculeatus on birch xylan and wheat arabinoxylan. Results are
      discussed in the light of a critical analysis of the sensitivity of four chemical
      reducing-end quantification methods using well-characterized substrates.

PMID- 21074511
TI  - Protection by alpha-tocopherol of the repair of photosystem II during
      photoinhibition in Synechocystis sp. PCC 6803.
AB  - alpha-Tocopherol is a lipophilic antioxidant that is an efficient scavenger of
      singlet oxygen. We investigated the role of alpha-tocopherol in the protection of
      photosystem II (PSII) from photoinhibition using a mutant of the cyanobacterium
      Synechocystis sp. PCC 6803 that is deficient in the biosynthesis of alpha
      tocopherol. The activity of PSII in mutant cells was more sensitive to
      inactivation by strong light than that in wild-type cells, indicating that lack
      of alpha-tocopherol enhances the extent of photoinhibition. However, the rate of
      photodamage to PSII, as measured in the presence of chloramphenicol, which blocks
      the repair of PSII, did not differ between the two lines of cells. By contrast,
      the repair of PSII from photodamage was suppressed in mutant cells. Addition of
      alpha-tocopherol to cultures of mutant cells returned the extent of
      photoinhibition to that in wild-type cells, without any effect on photodamage.
      The synthesis de novo of various proteins, including the D1 protein that plays a
      central role in the repair of PSII, was suppressed in mutant cells under strong
      light. These observations suggest that alpha-tocopherol promotes the repair of
      photodamaged PSII by protecting the synthesis de novo of the proteins that are
      required for recovery from inhibition by singlet oxygen.

PMID- 21074513
TI  - Identification and functional characterization of uric acid transporter Urat1
      (Slc22a12) in rats.
AB  - Uric acid transporter URAT1 contributes significantly to reabsorption of uric
      acid in humans to maintain a constant serum uric acid (SUA) level. Since
      alteration of SUA level is associated with various diseases, it is important to
      clarify the mechanism of change in SUA. However, although expression of mRNA of
      an ortholog of URAT1 (rUrat1) in rats has been reported, functional analysis and
      localization have not been done. Therefore, rat rUrat1 was functionally analyzed
      using gene expression systems and isolated brush-border membrane vesicles (BBMVs)
      prepared from rat kidney, and its localization in kidney was examined
      immunohistochemically. Uric acid transport by rUrat1 was chloride (Cl-)
      susceptible with a Km of 1773MUM. It was inhibited by benzbromarone and trans
      stimulated by lactate and pyrazinecarboxylic acid (PZA). Cl- gradient-susceptible
      uric acid transport by BBMVs showed similar characteristics to those of uric acid
      transport by rUrat1. Moreover, rUrat1 was localized at the apical membrane in
      proximal tubular epithelial cells in rat kidney. Accordingly, rUrat1 is
      considered to be involved in uric acid reabsorption in rats in the same manner as
      URAT1 in humans. Therefore, rUrat1 may be a useful model to study issues related
      to the role of human URAT1.

PMID- 21074514
TI  - Functional analysis of the conserved hydrophobic gate region of the magnesium
      transporter CorA.
AB  - The Leu294 residue in the cytoplasmic neck of Thermotoga maritima CorA is
      considered to be the main gate for Mg2+ transport. We created three site-directed
      mutants at this position: in the Leu294Asp and Leu294Gly mutants we observed a
      defect in closing of the pore, while in the Leu294Arg mutant not only gating, but
      also the regulation of Mg2+ uptake was affected. Our results confirmed the
      importance of the Leu294 for gating of Mg2+ transport and in addition revealed
      the influence of the charge and structural features of the amino acid residues on
      the gating mechanism.

PMID- 21074512
TI  - Genetic insights into OXPHOS defect and its role in cancer.
AB  - Warburg proposed that cancer originates from irreversible injury to mitochondrial
      oxidative phosphorylation (mtOXPHOS), which leads to an increase rate of aerobic
      glycolysis in most cancers. However, despite several decades of research related
      to Warburg effect, very little is known about the underlying genetic cause(s) of
      mtOXPHOS impairment in cancers. Proteins that participate in mtOXPHOS are encoded
      by both mitochondrial DNA (mtDNA) as well as nuclear DNA. This review describes
      mutations in mtDNA and reduced mtDNA copy number, which contribute to OXPHOS
      defects in cancer cells. Maternally inherited mtDNA renders susceptibility to
      cancer, and mutation in the nuclear encoded genes causes defects in mtOXPHOS
      system. Mitochondria damage checkpoint (mitocheckpoint) induces epigenomic
      changes in the nucleus, which can reverse injury to OXPHOS. However, irreversible
      injury to OXPHOS can lead to persistent mitochondrial dysfunction inducing
      genetic instability in the nuclear genome. Together, we propose that
      "mitocheckpoint" led epigenomic and genomic changes must play a key role in
      reversible and irreversible injury to OXPHOS described by Warburg. These
      epigenetic and genetic changes underlie the Warburg phenotype, which contributes
      to the development of cancer.

PMID- 21074515
TI  - Structure and metal ion binding of the first transmembrane domain of DMT1.
AB  - DMT1 is an integral membrane protein with 12 putative transmembrane domains. As a
      divalent metal ion transporter, it plays an important role in metal ion
      homeostasis from bacteria to human. Loss-function mutations at the conserved
      motif DPGN located within the first transmembrane domain (TMD1) of DMT1 indicate
      the significance of TMD1 in the biological function of the protein. In the
      present work, we study the structure, topology and metal ion binding of DMT1-TMD1
      peptide by nuclear magnetic resonance using sodium dodecyl sulfate and
      dodecylphosphocholine micelles as membrane mimics. We find that the peptide forms
      an alpha-helix-extended segment-alpha-helix configuration in which the motif DPGN
      locates at the central flexible region. The N-terminal part of the peptide is
      deeply embedded in micelles, while the motif section and the C-terminal part are
      close to the surface of micelles. The peptide can bind to Mn2+ and Co2+ ions by
      the side chains of the negatively charged residues in the motif section and the C
      terminal part of TMD1. The crucial role of the central flexible region and the C
      terminal part of TMD1 in metal ion capture is confirmed by the binding of the N
      terminal part truncated TMD1 to metal ions.

PMID- 21074516
TI  - Biological characterization and structure based prediction of insulin-like growth
      factor binding protein-5.
AB  - The insulin-like growth factor binding protein (IGFBP) family has been shown to
      play a role in various functions such as cell growth, cell death, cell motility,
      and tissue remodeling. Among the 7 IGFBP family members, IGFBP-5 was recently
      shown to play an important role in breast cancer biology, especially in breast
      cancer metastasis. The three-dimensional structure of the mini IGFBP-5 domain
      (amino acids 40-92) is known, but structural information on the complete N, L,
      and C domains remains unknown. Due to difficulties associated with expression and
      crystallization of full-length IGFBP-5, fragments have more frequently been
      studied. In this study, IGFBP-5 structures containing N, L, and C domains were
      separately modeled from solved structures in protein data bank (PDB). In
      addition, the L domain of IGFBP-5 was expressed in Escherichia coli and purified
      for studying its structural characterization. Despite very low sequence homology,
      the novel L domain structure of IGFBP-5 was unexpectedly similar to that of the
      corepressor of repressor element-1 silencing transcription factor (CoREST) linker
      in the lysine-specific demethylase 1 (LSD1)-CoREST complex. The purified L domain
      existed as a homogenous dimer in glutaraldehyde cross-linking and exhibited a
      typical alpha-helix structure in the circular dichroism (CD) assay. This study
      has potential applications in medicine and other fields such as drug design,
      mutational study, and disease prediction.

PMID- 21074517
TI  - Gambogic acid inhibits Hsp90 and deregulates TNF-alpha/NF-kappaB in HeLa cells.
AB  - Gambogic acid (GB) is an important anti-cancer drug candidate, but the target
      protein by which it exerts its anti-cancer effects has not been identified. This
      study is the first to show that GB inhibits heat shock protein 90 (Hsp90) and
      down-regulates TNF-alpha/NF-kappaB in HeLa cells. The effects of GB on Hsp90 were
      studied by characterizing its physical interactions with Hsp90 upon binding, the
      noncompetitive inhibition of Hsp90 ATPase activity, and the degradation of Hsp90
      client proteins (i.e., Akt, IKK) in HeLa cells. GB seems to bind to the N
      terminal ATP-binding domain of Hsp90. Additionally, GB suppresses the activation
      of TNF-alpha/NF-kappaB and decreases XIAP expression levels and the ratio of Bcl
      2/Bax, which in turn induces HeLa cell apoptosis. Thus, GB represents a promising
      therapeutic agent for cancer; it may also be useful as a probe to increase
      understanding of the biological functions of Hsp90.

PMID- 21074518
TI  - mtDNA m.3635G>A may be classified as a common primary mutation for Leber
      hereditary optic neuropathy in the Chinese population.
AB  - Leber hereditary optic neuropathy (LHON) is the most common cause of sudden
      blindness in young adults and is caused by mtDNA mutations. At least 30 mutations
      have been identified but only the three common mutations (m.3460G>A, m.11778G>A,
      and m.14484T>C) have been extensively studied. Most other mutations, including
      m.3635G>A, are considered as potential candidate LHON mutations due to a lack of
      enough evidence. The frequency of these potential candidate mutations in
      populations has not been determined. In this study, we performed a comprehensive
      survey of m.3635G>A in 1398 unrelated probands suspected to have LHON and
      detected the m.3635G>A mutation in 8 cases, including 4 probands with a family
      history of LHON. The mutation in 7 cases was homoplasmic, but the mutation in one
      patient was heteroplasmic. Patients with the m.3635G>A mutation demonstrated the
      typical phenotype of LHON. Our results provide strong evidence that similar to
      m.3460G>A, m.3635G>A is a pathogenic and common LHON mutation in the Chinese
      population.

PMID- 21074519
TI  - Risk assessment and mitigation strategies for reactive metabolites in drug
      discovery and development.
AB  - Drug toxicity is a leading cause of attrition of candidate drugs during drug
      development as well as of withdrawal of drugs post-licensing due to adverse drug
      reactions in man. These adverse drug reactions cause a broad range of clinically
      severe conditions including both highly reproducible and dose dependent
      toxicities as well as relatively infrequent and idiosyncratic adverse events. The
      underlying risk factors can be split into two groups: (1) drug-related and (2)
      patient-related. The drug-related risk factors include metabolic factors that
      determine the propensity of a molecule to form toxic reactive metabolites (RMs),
      and the RM and non-RM mediated mechanisms which cause cell and tissue injury.
      Patient related risk factors may vary markedly between individuals, and encompass
      genetic and non-genetic processes, e.g. environmental, that influence the
      disposition of drugs and their metabolites, the nature of the adverse responses
      elicited and the resulting biological consequences. We describe a new strategy,
      which builds upon the strategies used currently within numerous pharmaceutical
      companies to avoid and minimize RM formation during drug discovery, and that is
      intended to reduce the likelihood that candidate drugs will cause toxicity in the
      human population. The new strategy addresses drug-related safety hazards, but not
      patient-related risk factors. A common target organ of toxicity is the liver and
      to decrease the likelihood that candidate drugs will cause liver toxicity (both
      non-idiosyncratic and idiosyncratic), we propose use of an in vitro Hepatic
      Liability Panel alongside in vitro methods for the detection of RMs. This will
      enable design and selection of compounds in discovery that have reduced
      propensity to cause liver toxicity. In vitro Hepatic Liability is assessed using
      toxicity assays that quantify: CYP 450 dependent and CYP 450 independent cell
      toxicity; mitochondrial impairment; and inhibition of the Bile Salt Export Pump.
      Prior to progression into development, a Hepatotoxicity Hazard Matrix combines
      data from the Hepatic Liability Panel with the Estimated RM Body Burden. The
      latter is defined as the level of covalent binding of radiolabelled drug to human
      hepatocyte proteins in vitro adjusted for the predicted human dose. We exemplify
      the potential value of this approach by consideration of the thiazolidinedione
      class of drugs.

PMID- 21074520
TI  - Extension of a PBPK model for ethylene glycol and glycolic acid to include the
      competitive formation and clearance of metabolites associated with kidney
      toxicity in rats and humans.
AB  - A previously developed PBPK model for ethylene glycol and glycolic acid was
      extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium
      oxalate that is associated with kidney toxicity in rats and humans. The
      development and evaluation of the PBPK model was based upon previously published
      pharmacokinetic studies coupled with measured blood and tissue partition
      coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid,
      glycine and other metabolites using primary hepatocytes isolated from male Wistar
      rats and humans. Precipitation of oxalic acid with calcium in the kidneys was
      assumed to occur only at concentrations exceeding the thermodynamic solubility
      product for calcium oxalate. This solubility product can be affected by local
      concentrations of calcium and other ions that are expressed in the model using an
      ion activity product estimated from toxicity studies such that calcium oxalate
      precipitation would be minimal at dietary exposures below the NOAEL for kidney
      toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts
      that bolus oral or dietary exposures to ethylene glycol would result in typically
      1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium
      oxalate in kidneys of humans as compared with comparably exposed male Wistar rats
      over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to
      have greater oxalate levels in the kidneys than humans) was found for inhalation
      exposures although no accumulation of calcium oxalate is predicted to occur until
      exposures are well in excess of the theoretical saturated vapor concentration of
      200mg/m(3). While the current model is capable of such cross-species, dose, and
      route-of-exposure comparisons, it also highlights several areas of potential
      research that will improve confidence in such predictions, especially at low
      doses relevant for most human exposures.

PMID- 21074521
TI  - Closely related oxidized phospholipids differentially modulate the
      physicochemical properties of lipid particles.
AB  - Oxidation of glycerophospholipids results in the formation of large variety of
      oxidized phospholipid products that differs significantly in their chemical
      compositions and molecular structures. Biological activities of these oxidized
      products also differ considerably. Here we report the comparisons of the
      physicochemical properties of non-oxidized phospholipid particle containing two
      closely related tOx-PLs: 1-palmitoyl-2-(5-keto-6-octendioyl)-sn-glycero-3
      phosphocholine (KOdiA-PC) and 1-palmitoyl-2-(9-keto-10-dodecendioyl)-sn-glycero-3
      phosphocholine (KDdiA-PC). DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) was
      used as a model membrane non-oxidized phospholipid. Physicochemical properties of
      the lipid particles were characterized by using fluorescence spectroscopy, native
      polyacrylamide gel and agarose gel electrophoresis. Our result shows that the
      presence of closely related tOx-PLs, which differ only in the chemical
      composition of the oxidized fatty acyl chains at the sn-2 position, exerts
      considerably different effect on the physicochemical properties of non-oxidized
      phospholipid particles containing them.

PMID- 21074522
TI  - "All that glisters is not gold": Ultrafiltration and free thyroxine measurement
      With apologies to W Shakespeare.
AB  - OBJECTIVE: To examine the merits of measuring free analytes by ultrafiltration
      using either diluted or undiluted serum. RESULTS: Confidence in the accuracy of
      measurements is affected both by problems identified in current systems using
      semipermeable membranes, the sensitivity of the system to artefacts and
      comparisons with other imperfect assays. CONCLUSION: All "gold standard" methods
      must robustly obey sound physicochemical principles if valid conclusions are to
      be drawn.

PMID- 21074523
TI  - FGF signaling gradient maintains symmetrical proliferative divisions of midbrain
      neuronal progenitors.
AB  - For the correct development of the central nervous system, the balance between
      self-renewing and differentiating divisions of the neuronal progenitors must be
      tightly regulated. To maintain their self-renewing identity, the progenitors need
      to retain both apical and basal interfaces. However, the identities of fate
      determining signals which cells receive via these connections, and the exact
      mechanism of their action, are poorly understood. The conditional inactivation of
      Fibroblast growth factor (FGF) receptors 1 and 2 in the embryonic mouse midbrain
      hindbrain area results in premature neuronal differentiation. Here, we aim to
      elucidate the connection between FGF signaling and neuronal progenitor
      maintenance. Our results reveal that the loss of FGF signaling leads to
      downregulation of Hes1 and upregulation of Ngn2, Dll1, and p57 in the ventricular
      zone (VZ) cells, and that this increased neurogenesis occurs cell-autonomously.
      Yet the cell cycle progression, apico-basal-polarity, cell-cell connections, and
      the positioning of mitotic spindle in the mutant VZ appear unaltered.
      Interestingly, FGF8-protein is highly concentrated in the basal lamina. Thus,
      FGFs may act through basal processes of neuronal progenitors to maintain their
      progenitor status. Indeed, midbrain neuronal progenitors deprived in vitro of
      FGFs switched from symmetrical proliferative towards symmetrical neurogenic
      divisions. We suggest that FGF signaling in the midbrain VZ is cell-autonomously
      required for the maintenance of symmetrical proliferative divisions via Hes1
      mediated repression of neurogenic genes.

PMID- 21074524
TI  - Differential requirements for neurogenin 3 in the development of POMC and NPY
      neurons in the hypothalamus.
AB  - The neuroendocrine hypothalamus regulates a spectrum of essential biological
      processes and underlies a range of diseases from growth failure to obesity. While
      the exploration of hypothalamic function has progressed well, knowledge of
      hypothalamic development is poor. In particular, very little is known about the
      processes underlying the genesis and specification of the neurons in the arcuate
      and ventromedial nuclei. Recent studies demonstrate that the proneural basic
      helix-loop-helix transcription factor Mash1 is required for neurogenesis and
      neuronal subtype specification in the ventral hypothalamus. We demonstrate here
      that Ngn3, another basic helix-loop-helix transcription factor, is expressed in
      mitotic progenitors in the arcuate and ventromedial hypothalamic regions of mouse
      embryos from embryonic days 9.5-17.5. Genetic fate mapping and loss of function
      studies in mice demonstrate that Ngn3+ progenitors contribute to subsets of POMC,
      NPY, TH and SF1 neurons and is required for the specification of these neuronal
      subtypes in the ventral hypothalamus. Interestingly, while Ngn3 promotes the
      development of arcuate POMC and ventromedial SF1 neurons, it inhibits the
      development of NPY and TH neurons in the arcuate nuclei. Given the opposing roles
      of POMC and NPY neurons in regulating food intake, these results indicate that
      Ngn3 plays a central role in the generation of neuronal populations controlling
      energy homeostasis in mice.

PMID- 21074525
TI  - Inhibition of cell survival, invasion, tumor growth and histone deacetylase
      activity by the dietary flavonoid luteolin in human epithelioid cancer cells.
AB  - Phytochemical compounds and histone deacetylase (HDAC) inhibitors are emerging as
      a new generation of anticancer agents with limited toxicity in cancer patients.
      We investigated the impact of luteolin, a dietary flavonoid, on survival,
      migration, invasion of cancer cells in vitro, and tumor growth in vivo. Luteolin
      (25-200MUM) decreased the viability of human cancer cell lines originating from
      the lung (LNM35), colon (HT29), liver (HepG2) and breast (MCF7/6 and MDA-MB231
      1833). Luteolin effectively increased the sub-G1 (apoptotic) fraction of cells
      through caspase-3 and -7 dependent pathways. We provide evidence that luteolin at
      sub-lethal/non-toxic concentrations inhibited the invasive potential of LNM35,
      MCF-7/6 and MDA-MB231-1833 cancer cells using Matrigel as well as the chick heart
      and Oris invasion assays. Moreover, we demonstrate for the first time that
      luteolin is a potent HDAC inhibitor that potentiates the cytotoxicity of
      cisplatin in LNM35 cells and decreases the growth of LNM35 tumor xenografts in
      athymic mice after intraperitoneal injection (20mg/kg/day for 18days) Thus,
      luteolin, in combination with standard anticancer drugs such as cisplatin, may be
      a promising HDAC inhibitor for the treatment of lung cancer.

PMID- 21074526
TI  - Touchdown-touchup nested PCR for low-copy gene detection of benzimidazole
      susceptible Wuchereria bancrofti with a Wolbachia endosymbiont imported by
      migrant carriers.
AB  - A novel, sensitive and specific touchdown-touchup nested PCR (TNPCR) technique
      based on two useful molecular markers, a Wuchereria bancrofti beta-tubulin gene
      involved in benzimidazole susceptibility and a Wolbachia ftsZ gene involved in
      cell division, was developed to simultaneously detect the parasite W. bancrofti
      (W1) with its Wolbachia endosymbiont (W2) from both microfilaremic and post
      treatment samples of at-risk migrant carriers infected with geographical W.
      bancrofti isolates. The detection and characterization of authentically low-copy
      gene-derived amplicons revealed no false positive identifications in
      amicrofilaremia with or without antigenemia. The W1-TNPCR was 100-fold more
      sensitive than the W2-TNPCR regardless of the microfilarial DNA isolation method
      and compared well with the thick blood film and membrane filtration techniques.
      These locus-specific TNPCRs could also detect Wolbachia-carrying W. bancrofti
      genotype in addition to a link to benzimidazole sensitivity among those with
      unknown infection origins that exhibited microfilaremia responsiveness against
      treatment with diethylcarbamazine plus albendazole. These TNPCR methods can
      augment the results of microscopic detection of the parasite because these
      methods enhance DNA isolation and PCR amplification capabilities.

PMID- 21074528
TI  - Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase
      in diverse tissues from mice.
AB  - We examined the effects of lactate on the enzymatic activity of hexokinase (HK),
      phosphofructokinase (PFK) and pyruvate kinase (PK) in various mouse tissues. Our
      results showed that lactate inhibited PFK activity in all the analyzed tissues.
      This inhibitory effect was observed in skeletal muscle even in the presence of
      insulin. Lactate directly inhibited the phosphorylation of PFK tyrosine residues
      in skeletal muscle, an important mechanism of the enzyme activation. Moreover,
      lactate indirectly inhibited HK activity, which resulted from its cellular
      redistribution, here attributed to alterations of HK structure. PK activity was
      not affected by lactate. The activity of HK and PFK is directly related to
      glucose metabolism. Thus, it is conceivable that lactate exposure can induce
      inhibition of glucose consumption in tissues.

PMID- 21074527
TI  - Histone arginine methylation.
AB  - Arginine methylation is a common posttranslational modification (PTM). This type
      of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly
      abundant on shuttling proteins. In this review, we will focus on one aspect of
      this PTM: the diverse roles that arginine methylation of the core histone tails
      play in regulating chromatin function. A family of nine protein arginine
      methyltransferases (PRMTs) catalyze methylation reactions, and a subset target
      histones. Importantly, arginine methylation of histone tails can promote or
      prevent the docking of key transcriptional effector molecules, thus playing a
      central role in the orchestration of the histone code.

PMID- 21074529
TI  - Functional analysis of propeptide as an intramolecular chaperone for in vivo
      folding of subtilisin nattokinase.
AB  - Here, we show that during in vivo folding of the precursor, the propeptide of
      subtilisin nattokinase functions as an intramolecular chaperone (IMC) that
      organises the in vivo folding of the subtilisin domain. Two residues belonging to
      beta-strands formed by conserved regions of the IMC are crucial for the folding
      of the subtilisin domain through direct interactions. An identical protease can
      fold into different conformations in vivo due to the action of a mutated IMC,
      resulting in different kinetic parameters. Some interfacial changes involving
      conserved regions, even those induced by the subtilisin domain, blocked
      subtilisin folding and altered its conformation. Insight into the interaction
      between the subtilisin and IMC domains is provided by a three-dimensional
      structural model.

PMID- 21074530
TI  - Signalling by immunoreceptors.

PMID- 21074531
TI  - The bovine genome contains three differentially methylated paralogous copies of
      the P450c17 encoding gene (CYP17A1).
AB  - CYP17A1 encodes the key enzyme of androgen biosynthesis, P450c17. The gene is
      expressed in a number of steroidogenic tissues among them testis, ovary, placenta
      and adrenal gland. The proper analysis of CYP17A1 expression and of epigenetic
      parameters however, is hampered by the presence of more than one copy of the gene
      within the bovine genome. Therefore, as a prerequisite for future studies we
      characterized these copies and analyzed their promoter methylation and expression
      profiles in different tissues. DNA methylation levels were determined by
      bisulfite modification, amplification, cloning and sequencing. Transcription was
      analyzed by RT-PCR. From bovine genomic DNA three different CYP17A1 promoter
      sequences could be amplified with a sequence similarity of 94.8%, 95.6% and
      98.7%. Based on these sequences we could reconstruct, by in silico analysis, the
      promoter regions and eight potentially coding exons of two loci, CYP17A1a and
      CYP17A1b, and the promoter region and truncated first exon of a third locus,
      CYP17A1x. By using locus-specific primers, only transcripts of CYP17A1a, but not
      of CYP17A1b could be detected in testis, epididymis, theca, corpus luteum,
      placental cotyledons, adrenal gland and preoptic brain area. Methylation analysis
      revealed that only the CYP17A1a promoter was hypo-methylated in the tested
      P450c17 active tissues, whereas both other copies showed higher levels of
      methylation. From these data we conclude that the bovine genome contains three
      paralogous copies of the CYP17A1 gene, of which two (CYP17A1b and CYP17A1x) might
      be silenced by epigenetic modification (promoter methylation).

PMID- 21074532
TI  - The glucocorticoid stress response is attenuated but unrelated to reproductive
      investment during parental care in a teleost fish.
AB  - We investigated whether circulating glucocorticoids and androgens are correlated
      with reproductive investment in smallmouth bass (Micropterus dolomieu), a teleost
      fish with sole paternal care. Circulating cortisol and androgens prior to and 25
      min following a standardized 3 min emersion stressor were quantified for non
      reproductive and parental fish across the parental care period. To experimentally
      investigate the influence of reproductive investment on endocrine parameters, we
      manipulated brood size (reduced, enlarged, sham-treated, or unmanipulated) 24h
      prior to sampling parental fish. We predicted that fish guarding offspring would
      exhibit increased androgens and baseline cortisol levels, and an attenuated
      cortisol response to the stressor when compared with non-reproductive
      individuals. We further predicted that these effects would scale with
      reproductive investment. As predicted, parental care-providing fish exhibited
      lower post-stress plasma cortisol concentrations than non-reproductive fish. This
      difference was strongest early during parental care. However, no differences in
      baseline or post-stress cortisol concentrations were detected among parents
      guarding offspring with varying brood sizes. There was, however, a trend for
      parental fish to exhibit an increased cortisol response following brood
      manipulation, regardless of the direction of change in brood size, a response
      that likely reflected disturbance. No differences were found in baseline cortisol
      concentrations. Circulating androgens were found to be highest during early
      parental care, and no differences were found among parents guarding manipulated
      broods. Collectively, these findings demonstrate that the endocrine stress
      response is affected by reproductive status, but the response in this model
      species does not appear to be scaled according to reproductive investment as
      predicted by life-history theory.

PMID- 21074533
TI  - Bioinformatic prediction of arthropod/nematode-like peptides in non-arthropod,
      non-nematode members of the Ecdysozoa.
AB  - The Onychophora, Priapulida and Tardigrada, along with the Arthropoda, Nematoda
      and several other small phyla, form the superphylum Ecdysozoa. Numerous
      peptidomic studies have been undertaken for both the arthropods and nematodes,
      resulting in the identification of many peptides from each group. In contrast,
      little is known about the peptides used as paracrines/hormones by species from
      the other ecdysozoan taxa. Here, transcriptome mining and bioinformatic peptide
      prediction were used to identify peptides in members of the Onychophora,
      Priapulida and Tardigrada, the only non-arthropod, non-nematode members of the
      Ecdysozoa for which there are publicly accessible expressed sequence tags (ESTs).
      The extant ESTs for each phylum were queried using 106 arthropod/nematode peptide
      precursors. Transcripts encoding calcitonin-like diuretic hormone and pigment
      dispersing hormone (PDH) were identified for the onychophoran Peripatopsis
      sedgwicki, with transcripts encoding C-type allatostatin (C-AST) and FMRFamide
      like peptide identified for the priapulid Priapulus caudatus. For the Tardigrada,
      transcripts encoding members of the A-type allatostatin, C-AST, insect kinin,
      orcokinin, PDH and tachykinin-related peptide families were identified, all but
      one from Hypsibius dujardini (the exception being a Milnesium tardigradum
      orcokinin-encoding transcript). The proteins deduced from these ESTs resulted in
      the prediction of 48 novel peptides, six onychophoran, eight priapulid and 34
      tardigrade, which are the first described from these phyla.

PMID- 21074534
TI  - The hypothalamic-pituitary-ovarian axis and manipulations of the oestrous cycle
      in the brushtail possum.
AB  - The main purpose of this review is to provide a comprehensive update on what is
      known about the regulatory mechanisms of the hypothalamic-pituitary-ovarian axis
      in the brushtail possum, and to report on the outcomes of attempts made to
      manipulate by hormonal means, these processes in the possum. Over the last 15
      years, several unique features of possum reproductive physiology have been
      discovered. These include an extended follicular phase despite elevated
      concentrations of FSH during the luteal phase, and early expression of LH
      receptors on granulosa cells of small antral follicles, suggesting a different
      mechanism for the selection of a dominant follicle. The use of routine
      synchronisation protocols that are effective in eutherians has failed to be
      effective in possums, and so the ability to reliably synchronise oestrus in this
      species remains a challenge.

PMID- 21074535
TI  - Evolution of the parathyroid hormone family and skeletal formation pathways.
AB  - Bone is considered to be a feature of higher vertebrates and one of the features
      that was required for the movement from water onto land. But there are a number
      of evolutionarily important species that have cartilaginous skeletons, including
      sharks. Both bony and cartilaginous fish are believed to have a common ancestor
      who had a bony skeleton. A number of factors and pathways have been shown to be
      involved in the development and maintenance of bony skeleton including the Wnt
      pathway and the parathyroid hormone gene family. The study of these pathways and
      factors in cartilaginous animals may shed light on the evolution of the
      vertebrate skeleton.

PMID- 21074536
TI  - Transcriptional changes in Giardia during host-parasite interactions.
AB  - Giardia intestinalis is one of the major causes of parasite-induced diarrhea. The
      disease, giardiasis, is caused by trophozoites attaching to the intestinal
      epithelium, resulting in apoptosis of intestinal epithelial cells, disrupted
      epithelial barrier function and malabsorption. Microarray studies have detected
      extensive gene expression changes in intestinal epithelial cells (IECs) during
      interaction with Giardia trophozoites in vitro. In the present study, we examined
      this host-parasite interaction further by transcriptional profiling of
      interacting trophozoites using Giardia microarrays. A total of 200 Giardia
      transcripts were significantly changed due to the interaction, lasting up to 18 h
      in complete growth medium. Quantitative reverse transcriptase PCR confirmed the
      changes in all 12 genes tested using mRNA isolated in separate experiments. Genes
      encoding proteins previously suggested to be important during host-parasite
      interactions such as arginine deiminase, enolase and cysteine proteinases were up
      regulated early but down-regulated later during the interaction. Cell division
      and attachment genes were down-regulated in the late time-points of interaction.
      The most highly up-regulated genes encode oxygen defense proteins and several
      members of the high cysteine membrane protein (HCMp) and Gly-rich repeat (GRREAT)
      families. Putative small RNAs were up-regulated, whereas the 5S rRNA was slightly
      down-regulated during the interaction with IECs. Thus, there are extensive gene
      expression changes in Giardia trophozoites and IECs during host-parasite
      interactions which can be important for establishment of infection and the
      induction of giardiasis.

PMID- 21074537
TI  - Primum non nocere: when will ryanodine receptor leak find its role in heart
      failure?

PMID- 21074539
TI  - Inhibition of p53 after acute myocardial infarction: reduction of apoptosis is
      counteracted by disturbed scar formation and cardiac rupture.
AB  - Cardiomyocyte apoptosis, partially mediated through p53 signaling pathway, plays
      a crucial role in the progression of pathological remodeling and heart failure
      following myocardial infarction (MI). We hypothesized that pifithrin-alpha
      (PFTa), a synthetic p53 inhibitor, would suppress cardiac apoptosis through the
      disruption of p53-dependent transcriptional activation and thereby improve heart
      function in a mouse model of MI. In our experiments we show that PFTa blocked p53
      transcriptional activity and attenuated H(2)O(2)-induced cardiac apoptosis in
      cultured neonatal rat cardiomyocytes. Additionally, administration of PFTa in
      mice after acute MI in vivo led to a significant reduction of cardiomyocyte
      apoptosis but in parallel caused an increase of infarct size and significantly
      reduced 7-day survival rate. Subsequent analysis revealed significantly reduced
      proliferation and cell number, diminished collagen deposition, and elevated MMP-2
      activity at the infarct zone of PFTa-treated hearts. In homozygous p53 deficient
      mice (p53(-/-)), however, PFTa treatment did not interfere with scar formation
      and did not increase MMP-2 activity after MI. Collectively, our data suggest that
      although p53-inhibition through PFTa reduces cardiomyocyte apoptosis, in the
      setting of acute MI this assumed beneficial effect is severely counteracted by
      the adverse remodeling of the infarct zone. PFTa increases MMP-2 activity in a
      p53-dependent manner, which seems a major contributor to instability of the
      forming scar and consequently leads to infarct progression and ventricular
      rupture.

PMID- 21074538
TI  - Beta-arrestin: a signaling molecule and potential therapeutic target for heart
      failure.
AB  - Currently, some of the most effective treatments for heart failure target GPCRs
      such as the beta-adrenergic receptors (beta1AR and beta2AR) and angiotensin II
      type IA receptors (AT1aR). Ligands for these receptors not only function by
      blocking the deleterious G-protein mediated pathway leading to heart failure, but
      also signal via G-protein independent pathways that involve receptor
      phosphorylation by G-protein receptor kinases (GRKs) leading to recruitment of
      the multifunctional protein, beta-arrestin. Originally thought to play a role in
      GPCR desensitization and internalization, beta-arrestin has recently been shown
      to mediate signaling independent of classical second messengers in a way that is
      often protective to the heart. The multi-functionality of beta-arrestin makes it
      an intriguing molecule in the development of the next generation of drugs for
      cardiac diseases with the potential to simultaneously inhibit deleterious G
      protein dependent pathways while activating beneficial beta-arrestin mediated
      signaling. In this review, we explore various facets of beta-arrestin signaling
      and offer a perspective on its potential role as a key signaling molecule in the
      treatment of heart failure. This article is part of a special issue entitled "Key
      Signaling Molecules in Hypertrophy and Heart Failure."

PMID- 21074540
TI  - Thioredoxin 1 enhances neovascularization and reduces ventricular remodeling
      during chronic myocardial infarction: a study using thioredoxin 1 transgenic
      mice.
AB  - Oxidative stress plays a crucial role in disruption of neovascularization by
      alterations in thioredoxin 1 (Trx1) expression and its interaction with other
      proteins after myocardial infarction (MI). We previously showed that Trx1 has
      angiogenic properties, but the possible therapeutic significance of
      overexpressing Trx1 in chronic MI has not been elucidated. Therefore, we explored
      the angiogenic and cardioprotective potential of Trx1 in an in vivo MI model
      using transgenic mice overexpressing Trx1. Wild-type (W) and Trx1 transgenic
      (Trx1(Tg/+)) mice were randomized into W sham (WS), Trx1(Tg/+) sham (TS), WMI,
      and TMI. MI was induced by permanent occlusion of LAD coronary artery. Hearts
      from mice overexpressing Trx1 exhibited reduced fibrosis and oxidative stress and
      attenuated cardiomyocyte apoptosis along with increased vessel formation compared
      to WMI. We found significant inhibition of Trx1 regulating proteins, TXNIP and
      AKAP 12, and increased p-Akt, p-eNOS, p-GSK-3beta, HIF-1alpha, beta-catenin,
      VEGF, Bcl-2, and survivin expression in TMI compared to WMI. Echocardiography
      performed 30days after MI revealed significant improvement in myocardial
      functions in TMI compared to WMI. Our study identifies a potential role for Trx1
      overexpression and its association with its regulatory proteins TXNIP, AKAP12,
      and subsequent activation of Akt/GSK-3beta/beta-catenin/HIF-1alpha-mediated VEGF
      and eNOS expression in inducing angiogenesis and reduced ventricular remodeling.
      Hence, Trx1 and other proteins identified in our study may prove to be potential
      therapeutic targets in the treatment of ischemic heart disease.

PMID- 21074541
TI  - Therapeutic targeting of innate immunity in the failing heart.
AB  - Recent studies suggest that the heart possesses an intrinsic system that is
      intended to delimit tissue injury, as well as orchestrate homoeostatic responses
      within the heart. The extant literature suggests that this intrinsic stress
      response is mediated, at least in part, by a family of pattern recognition
      receptors that belong to the innate immune system, including CD14, the soluble
      pattern recognition receptor for lipopolysaccharide, and Toll-like receptors 2,
      3, 4, 5, 6, 7, and 9. Although this intrinsic stress response system provides a
      short-term adaptive response to tissue injury, the beneficial effects of this
      phylogenetically ancient system may be lost if myocardial expression of these
      molecules either becomes sustained and/or excessive, in which case the salutary
      effects of activation of these pathways are contravened by the known deleterious
      effects of inflammatory signaling. Herein we present new information with regard
      to activation of innate immune gene expression in the failing human heart, as
      well as review the novel TLR antagonists that are being developed for other
      indications outside of heart failure. This review will discuss the interesting
      possibility that the TLR pathway may represent a new target for the development
      of novel heart failure therapeutics. This article is part of a special issue
      entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

PMID- 21074542
TI  - Joint evolution of sex ratio and reproductive group size under local mate
      competition with inbreeding depression.
AB  - Local mate competition (LMC) may involve some amount of inbreeding between
      siblings. Because sib-mating is generally accompanied by inbreeding depression,
      natural selection may favor a reduced rate of sib-mating, possibly affecting the
      evolution of sex ratio and reproductive group size. The present study
      theoretically investigated the evolution of these traits under LMC in the
      presence of inbreeding depression. When the reproductive group size evolves, the
      determination mechanism of sex ratio is important because the timescale of the
      sex ratio response to reproductive group size can affect the evolutionary
      process. We consider a spectrum of sex ratio determination mechanisms from purely
      unconditional to purely conditional, including intermediate modes with various
      relative strengths of unconditional and conditional effects. This analysis
      revealed that both the evolutionarily stable reproductive group size and ratio of
      males increase with higher inbreeding depression and with a larger relative
      strength of an unconditional effect in sex ratio determination. Unexpectedly,
      when the sex ratio is controlled purely conditionally, the reproductive group
      size cannot exceed three even under the severest level of inbreeding depression
      (i.e., lethal effect). The present study reveals the conditions for LMC to evolve
      through the analysis of the joint evolution of reproductive group size and sex
      ratio.

PMID- 21074543
TI  - Dose-dependent toxic effects of high-dose estrogen on renal and cardiac injury in
      surgically postmenopausal mice.
AB  - AIMS: We previously found that in mice with experimental myocardial infarction
      (MI), 17beta-estradiol (E2) increased mortality and worsened cardiac remodeling
      and these deleterious effects were associated with renal enlargement and
      hydronephrosis in a dose-dependent manner. In the present study we questioned
      whether E2-induced renal damage predisposes to rather than results from its
      adverse effects on the heart. MAIN METHODS: Ovariectomized (ovx) mice received
      either placebo (P) or E2 at 0.02 (E2-L, low dose), 0.42 (E2-M, moderate dose) or
      4.2 MUg/d (E2-H, high dose) for 8 weeks. KEY FINDINGS: E2-L partially restored
      uterine weight and plasma estrogen levels without affecting heart, lung and liver
      weight, hemodynamic parameters, or heart and kidney morphology and function. E2-M
      restored normal uterine weight, but this was accompanied by a significant
      increase in kidney weight, albuminuria, glomerular matrix formation and markers
      for oxidative stress. E2-H increased uterine weight 4.5-fold and resulted in
      higher plasma creatinine levels, severe albuminuria, renal tubular dilatation,
      tubulointerstitial injury, hydronephrosis, glomerulosclerosis and oxidative
      stress. E2-H also caused ascites, hepatomegaly and fluid retention in the uterine
      horns but had no significant effect on blood pressure or heart function.
      SIGNIFICANCE: Our data demonstrated that an excessive dose of E2 that raises
      uterine weight beyond physiological levels adversely affects the kidney even
      before it damages the heart. We believe estrogen dosage should be taken into
      account when considering hormonal replacement therapy, since inappropriate doses
      of E2 may damage not only the heart but also the kidney.

PMID- 21074544
TI  - Transcription inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole
      (DRB) causes DNA damage and triggers homologous recombination repair in mammalian
      cells.
AB  - Transcription, replication and homologous recombination are intrinsically
      connected and it is well established that an increase of transcription is
      associated with an increase in homologous recombination. Here, we have studied
      how homologous recombination is affected during transcription inhibition by 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a compound that prevents
      activating phosphorylations of the RNA Pol II C-terminal domain. We identify that
      DRB triggers an increase in homologous recombination within the hprt gene as well
      as increasing RAD51 foci formation in mammalian cells. Furthermore, we find that
      DRB-induced transcriptional stress is associated with formation of the nuclear
      foci of the phosphorylated form of H2AX (gammaH2AX). We accounted that about 72%
      of RAD51 foci co-localized with the observed gammaH2AX foci. Interestingly, we
      find that XRCC3 mutated, homologous recombination defective cells are
      hypersensitive to the toxic effect of DRB and fail to form RAD51 foci. In
      conclusion, we show that DRB-induced transcription inhibition is associated with
      the formation of a lesion that triggers RAD51-dependent homologous recombination
      repair, required for survival under transcriptional stress.

PMID- 21074546
TI  - Probes for studying cholesterol binding and cell biology.
AB  - Cholesterol is a multifunctional lipid in eukaryotic cells. It regulates the
      physical state of the phospholipid bilayer, is crucially involved in the
      formation of membrane microdomains, affects the activity of many membrane
      proteins, and is the precursor for steroid hormones and bile acids. Thus,
      cholesterol plays a profound role in the physiology and pathophysiology of
      eukaryotic cells. The cholesterol molecule has achieved evolutionary perfection
      to fulfill its different functions in membrane organization. Here, we review
      basic approaches to explore the interaction of cholesterol with proteins, with a
      particular focus on the high diversity of fluorescent and photoreactive
      cholesterol probes available today.

PMID- 21074545
TI  - Epigenetic GABAergic targets in schizophrenia and bipolar disorder.
AB  - It is becoming increasingly clear that a dysfunction of the
      GABAergic/glutamatergic network in telencephalic brain structures may be the
      pathogenetic mechanism underlying psychotic symptoms in schizophrenia (SZ) and
      bipolar (BP) disorder patients. Data obtained in Costa's laboratory (1996-2009)
      suggest that this dysfunction may be mediated primarily by a downregulation in
      the expression of GABAergic genes (e.g., glutamic acid decarboxylase67[GAD67] and
      reelin) associated with DNA methyltransferase (DNMT)-dependent hypermethylation
      of their promoters. A pharmacological strategy to reduce the hypermethylation of
      GABAergic promoters is to administer drugs, such as the histone deacetylase
      (HDAC) inhibitor valproate (VPA), that induce DNA-demethylation when administered
      at doses that facilitate chromatin remodeling. The benefits elicited by combining
      VPA with antipsychotics in the treatment of BP disorder suggest that an
      investigation of the epigenetic interaction of these drugs is warranted. Our
      studies in mice suggest that when associated with VPA, clinically relevant doses
      of clozapine elicit a synergistic potentiation of VPA-induced GABAergic promoter
      demethylation. Olanzapine and quetiapine (two clozapine congeners) also
      facilitate chromatin remodeling but at doses higher than used clinically, whereas
      haloperidol and risperidone are inactive. Hence, the synergistic potentiation of
      VPA's action on chromatin remodeling by clozapine appears to be a unique property
      of the dibenzepines and is independent of their action on catecholamine or
      serotonin receptors. By activating DNA-demethylation, the association of
      clozapine or its derivatives with VPA or other more potent and selective HDAC
      inhibitors may be considered a promising treatment strategy for normalizing
      GABAergic promoter hypermethylation and the GABAergic gene expression
      downregulation detected in the postmortem brain of SZ and BP disorder patients.
      This article is part of a Special Issue entitled 'Trends in neuropharmacology: in
      memory of Erminio Costa'.

PMID- 21074547
TI  - The effects of deoxynivalenol on gene expression in the murine thymus.
AB  - Deoxynivalenol (DON) is a mycotoxin produced by several Fusarium species and is
      often detected in grains. Because of its high abundance, there has been a large
      interest in the effects of DON in animals and humans. DON is known to be
      immunosuppressive at high concentrations and immunostimulatory at low
      concentrations. The present study aimed to acquire insight into the modes of
      action of DON. For this, C57Bl6 mice were orally exposed to 5, 10, or 25mg/kg bw
      DON for 3, 6, or 24h and thymuses were subjected to genome-wide expression
      microarray analysis. Gene set enrichment analysis (GSEA) demonstrated that DON
      downregulated genes involved in proliferation, mitochondria, protein synthesis,
      and ribosomal proteins. Furthermore, GSEA showed a selective downregulation of
      genes highly expressed at the early precursor thymocytes stage. This indicates
      that early precursor thymocytes, particularly at the double-positive CD4+CD8+
      stage, are more vulnerable to DON than very early or late precursor thymocytes.
      There was a large overlap of genes upregulated by DON with genes previously
      reported to be either upregulated during T cell activation or upregulated during
      negative selection of thymocytes that recognize "self-antigens". This indicates
      that DON induces cellular events that also occur after activation of the T cell
      receptor, for example, release of calcium from the endoplasmatic reticulum. This
      T cell activation in the thymus then evokes negative selection and depletion of
      thymocytes, which provides a plausible explanation for the high sensitivity of
      the thymus for DON exposure. The expression patterns of four genes indicative for
      some of the processes that were affected after DON treatment were confirmed using
      real-time PCR. Immunocytological experiments with primary mouse thymocytes
      demonstrated the translocation of NFAT from the cytoplasm into the nucleus upon
      exposure top DON, thus providing further evidence for the involvement of T cell
      activation.

PMID- 21074548
TI  - Cisplatin triggers atrophy of skeletal C2C12 myotubes via impairment of Akt
      signalling pathway and subsequent increment activity of proteasome and autophagy
      systems.
AB  - Cisplatin (cisPt) is an antineoplastic drug which causes an array of adverse
      effects on different organs and tissues, including skeletal muscle. In this work
      we show that cisPt behaves as a potent trigger to activate protein
      hypercatabolism in skeletal C2C12 myotubes. Within 24h of 50 MUM cisPt
      administration, C2C12 myotubes displayed unchanged cell viability but showed a
      subset of hallmark signs typically recognized during atrophy, including severe
      reduction in body size, repression of Akt phosphorylation, transcriptional up
      regulation of atrophy-related genes, such as atrogin-1, gabarap, beclin-1 and
      bnip-3, and loss of myogenic markers. As a consequence, proteasomal activity and
      formation of autophagosomes were remarkably increased in cisPt-treated myotubes,
      but forced stimulation of Akt pathway, as obtained through insulin administration
      or delivery of a constitutively activated Akt form, was sufficient to counter the
      cisPt-induced protein breakdown, leading to rescue of atrophic size. Overall,
      these results indicate that cisPt induces atrophy of C2C12 myotubes via
      activation of proteasome and autophagy systems, suggesting that the Akt pathway
      represents one sensitive target of cisPt molecular action in skeletal muscle.

PMID- 21074549
TI  - Visual bandwidths for face orientation increase during healthy aging.
AB  - Perception of visual motion declines during healthy aging, and evidence suggests
      that this reflects decreases in cortical GABA inhibition that increase neural
      noise and motion bandwidths. This is supported by neurophysiological data on
      motion perception in senescent monkeys. Much less is known about deficits in
      higher level form vision. For example, face perception of frontal views remains
      relatively constant from adolescence through age 70 with a modest decline
      thereafter. However, we have shown recently that the elderly have a specific
      deficit in face matching when a transformation must be made between frontal and
      left or right side views. Here we use face view adaptation to demonstrate that
      this deficit results from significant broadening of cortical bandwidths for face
      orientation along with increased internal noise. A neural model shows that these
      bandwidths increase by a factor of 1.74 between age 26 and age 67 years. This is
      similar to the increase reported for motion bandwidths in senescent monkeys.
      Furthermore, the neural model demonstrates that head orientation bandwidth
      increases can arise from decreased cortical inhibition. Thus, high levels of form
      vision degrade in parallel with higher levels of motion perception and likely
      result from similar causes.

PMID- 21074550
TI  - Molecular masses and sedimentation coefficients of extracellular hemoglobin of
      Glossoscolex paulistus: alkaline oligomeric dissociation.
AB  - The giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) has a
      molecular mass (M) of 3600+/-100 kDa and a standard sedimentation coefficient
      (s20,w0) of 58 S, estimated by analytical ultracentrifugation (AUC). In the
      present work, further AUC studies were developed for HbGp, at pH 10.0, which
      favors oligomeric dissociation into lower M species. The HbGp oligomer is formed
      by globin chains a, b, c and d plus the linker chains. The pure monomeric
      fraction, subunit d, and HbGp at pH 10.0, in the presence of beta
      mercaptoethanol, were also studied. Our results indicate that for samples of pure
      subunit d, besides the monomeric species with s20,w0 of 2.0 S, formation of dimer
      of subunit d is observed with s20,w0 of around 2.9 S. For the whole HbGp at pH
      10.0 contributions from monomers, trimers and linkers are observed. No
      contribution from 58 S species was observed for the sample of oxy-HbGp at pH
      10.0, showing its complete dissociation. For cyanomet-HbGp form a contribution of
      17% is observed for the un-dissociated oligomer, consistent with data from other
      techniques that show the cyanomet-form is more stable as compared to oxy-HbGp.
      Masses of HbGp subunits, especially trimer abc and monomeric chains a, b, c and
      d, were also estimated from sedimentation equilibrium data, and are in agreement
      with the results from MALDI-TOF-MS.

PMID- 21074551
TI  - Release of Cyt c from the model membrane due to conformational change induced by
      anticancer palladium complex.
AB  - Cytochrome C (Cyt c) is an electron transporting protein that resides within the
      inter-membrane space of the mitochondria. It plays a critical role as an electron
      carrier in the process of oxidative phosphorylation and production of cellular
      ATP. Cyt c is also involved in the apoptosis process and functions as a death
      messenger. On the other hand, it is well known that the metallo-pharmaceuticals
      such as palladium complex offer potential as anti-tumor agents to fight cancer.
      In order to identify the role of anticancer Pd complex in release of Cyt c from
      the biological membrane, an artificial monolayer was assembled which is able to
      adsorb Cyt c. A monolayer containing a mixture of two long chain thiols (mercapto
      undecanoic acid and mercapto-undecanol) was self-assembled on the surface of a
      gold electrode. Due to the existence of both hydrophobic and electrostatic
      interactions between Cyt c and the assembled monolayer, this membrane could be
      considered as a rough analogue of the biological membrane to study the release of
      Cyt c by Pd complex. The electrochemical and spectroscopic studies showed that
      bounding of Pd complex to Cyt c causes a conformational change which leads to the
      release of Cyt c from the model membrane.

PMID- 21074552
TI  - Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is
      altered by heavy metal exposure.
AB  - Pollution is a world problem with immeasurable consequences. Heavy metal
      compounds are frequently found as components of anthropogenic pollution. Here we
      evaluated the effects of the treatment with cadmium acetate, lead acetate,
      mercury chloride, and zinc chloride in acetylcholinesterase activity and gene
      expression pattern, as well as the effects of these treatments in antioxidant
      competence in the brain of an aquatic and well-established organism for
      toxicological analysis, zebrafish (Danio rerio, Cyprinidae). Mercury chloride and
      lead acetate promoted a significant decrease in acetylcholinesterase activity
      whereas they did not alter the gene expression pattern. In addition, the
      antioxidant competence was decreased after exposure to mercury chloride. The data
      presented here allowed us to hypothesize a signal transmission impairment,
      through alterations in cholinergic transmission, and also in the antioxidant
      competence of zebrafish brain tissue as some of the several effects elicited by
      these pollutants.

PMID- 21074553
TI  - Moving towards a new generation of animal models for asthma and COPD with
      improved clinical relevance.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are complex inflammatory
      airway diseases characterised by airflow obstruction that remain leading causes
      of hospitalization and death worldwide. Animal modelling systems that accurately
      reflect disease pathophysiology continue to be essential to the development of
      new therapies for both conditions. In this review, we describe preclinical in
      vivo models that recapitulate many of the features of asthma and COPD.
      Specifically, we discuss the pro's and con's of the standard models and highlight
      recently developed systems designed to more accurately reflect the complexity of
      both diseases. For instance, clinically relevant allergens (i.e. house dust mite)
      are now being used to mimic the inflammatory changes and airway remodelling that
      result after chronic allergen exposures. Additionally, systems are being
      developed to mimic steroid-resistant and viral exacerbations of allergic
      inflammation - aspects of asthma where there is an acute need for new therapies.
      Similarly, COPD models have evolved to align with the improved clinical
      understanding of the factors contributing to disease progression. This includes
      using cigarette smoke to model not only airway inflammation and remodelling, but
      some systemic changes (e.g. hypertension and skeletal muscle alterations) that
      are thought to influence disease. Further, mouse genetics are being exploited to
      gain insights into the genetics of COPD susceptibility. The new models of asthma
      and COPD described herein demonstrate that improved clinical understanding of the
      diseases and better preclinical models is an iterative process that will
      hopefully lead to therapies that can effectively manage severe asthma and COPD.

PMID- 21074555
TI  - Coherence between surface electromyograms is influenced by electrode placement in
      hand muscles.
AB  - We used multi-channel surface electromyograms (EMGs) to examine if electrode
      location influences coherence measures derived from pairs of EMGs recorded from
      two hand muscles during a pinch task. A linear probe of 16 electrodes was used to
      estimate the location of the innervation zone in first dorsal interosseous (FDI)
      and abductor pollicis brevis (APB). Four electrodes were then placed on the skin
      overlying each muscle and three bipolar electrode configurations were constructed
      with their center points directly over the innervation zone, and 15mm distal and
      proximal to the innervation zone. Ten subjects performed two force-matching tasks
      for 120s at 2N and 3.5N by pressing a force sensor held between the thumb and
      index finger. Coherence spectra were calculated from pairs of EMGs recorded from
      the two muscles. Maximal coherence from 1 to 15Hz and 16 to 32Hz was calculated
      at both force levels from the EMGs with electrodes centered over the innervation
      zones of FDI and APB. These values were compared to the maximal coherence from
      all other EMG comparisons across muscles recorded with electrodes that avoided
      the innervation zones. ANOVA revealed significant main effects only for electrode
      location, with a 58.1% increase (p=0.001) in maximal coherence for EMGs detected
      from pairs of electrodes that avoided the innervation zone (from 0.11+/-0.02 to
      0.18+/-0.03; mean+/-95% confidence interval). These results indicate that
      electrode location relative to the innervation zone influences EMG-EMG coherence
      and should be carefully considered when placing EMG electrodes on hand muscles.

PMID- 21074554
TI  - Group XV phospholipase A2, a lysosomal phospholipase A2.
AB  - A phospholipase A2 was identified from MDCK cell homogenates with broad
      specificity toward glycerophospholipids including phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. The
      phospholipase has the unique ability to transacylate short chain ceramides. This
      phospholipase is calcium-independent, localized to lysosomes, and has an acidic
      pH optimum. The enzyme was purified from bovine brain and found to be a water
      soluble glycoprotein consisting of a single peptide chain with a molecular weight
      of 45 kDa. The primary structure deduced from the DNA sequences is highly
      conserved between chordates. The enzyme was named lysosomal phospholipase A2
      (LPLA2) and subsequently designated group XV phospholipase A2. LPLA2 has 49% of
      amino acid sequence identity to lecithin-cholesterol acyltransferase and is a
      member of the alphabeta-hydrolase superfamily. LPLA2 is highly expressed in
      alveolar macrophages. A marked accumulation of glycerophospholipids and extensive
      lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed
      in alveolar macrophages in LPLA2(-/-) mice. This defect can also be reproduced in
      macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In
      addition, older LPLA2(-/-) mice develop a phenotype similar to human autoimmune
      disease. These observations indicate that LPLA2 may play a primary role in
      phospholipid homeostasis, drug toxicity, and host defense.

PMID- 21074556
TI  - Dual-labeling method for electron microscopy to characterize synaptic
      connectivity using genetically encoded fluorescent reporters in Drosophila.
AB  - Light and electron microscopy (LM and EM) both offer important advantages for
      characterizing neuronal circuitry in intact brains: LM can reveal the general
      patterns neurons trace between brain areas, and EM can confirm synaptic
      connections between identified neurons within a small area. In a few species,
      genetic labeling with fluorescent proteins has been used with LM to visualize
      many kinds of neurons and to analyze their morphologies and projection patterns.
      However, combining these large-scale patterns with the fine detail available in
      EM analysis has been a technical challenge. To analyze the synaptic connectivity
      of neurons expressing fluorescent markers with EM, we developed a dual-labeling
      method for use with pre-embedded brains. In Drosophila expressing genetic labels
      and also injected with markers we visualized synaptic connections among two
      populations of neurons in the AL, one of which has been shown to mediate a
      specific function, odor evoked neural oscillation.

PMID- 21074557
TI  - Evaluation of lumbosacral nerve root conduction in chickens by
      electrophysiological testing including high-resolution spinal magnetic
      stimulation.
AB  - The value of avian models in peripheral nerve research recently became
      substantiated by the immunobiological similarity of avian inflammatory
      demyelinating polyradiculoneuropathy to human Guillain-Barre syndrome providing
      an alternative animal model for experimental autoimmune neuritis. As
      electrophysiologic evaluation of nerve roots is essential part of the diagnosis
      of polyradiculoneuropathies in humans, it would be favourable to have similar
      research methods available for juvenile chickens. Hence, this study was performed
      (1) to establish a tool-set that allows for reproducible evaluation of the
      tibial/sciatic nerve and its nerve roots, (2) to achieve age-matched reference
      values, and (3) to trace the kinetics of peripheral nerve maturation within
      chickens. Nine chickens underwent serial electrodiagnostic examinations between
      the age of 6 and 15 weeks. Several methods of sensory and motor nerve fiber
      stimulation of the tibial/sciatic nerve were tested and modified or established.
      Ultimately, scalp-recorded somatosensory evoked potentials, compound muscle
      action potentials elicited by tibial/sciatic nerve electrical as well as spinal
      magnetic stimulation and motor nerve conduction velocity were available for
      tibial/sciatic nerve and nerve root evaluation in chickens. Base values were
      obtained for all investigations and parameters. Results indicated that the
      maturation of the nerve fibers is incomplete up to the age of 15 weeks. The
      methods tested here provide an excellent tool-set for quantitative tibial/sciatic
      nerve and nerve root assessment in avian polyradiculoneuropathies, especially
      within the scope of longitudinal monitoring of the disease course.

PMID- 21074558
TI  - Application of multidimensional scaling to quantify shape in Alzheimer's disease
      and its correlation with Mini Mental State Examination: a feasibility study.
AB  - Today, high-resolution MRI scans are able to reveal even the fine details of
      brain structure. Several methods have been developed to quantify shape
      differences specific to scans of diseased brains. We have developed a novel
      method for quantifying shape information based on multidimensional scaling (MDS),
      a well-known statistical tool. Multidimensional scaling uses distance measures
      computed from pair-wise image registration of the training set. Image
      registration establishes spatial correspondence between scans in order to compare
      them in the same spatial framework. Our novel method has several advantages,
      including robustness to errors in registrations. Applying our method to 44 brain
      MRIs showed clear separation between normal and Alzheimer scans. Using our method
      as basis for classification between normal and Alzheimer scans yielded better
      performance results compared with using the volume of hippocampus as basis for
      classification. We also devised a simple measure derived from the MDS approach
      that was shown to correlate with the Mini Mental State Examination (MMSE), a well
      known cognitive test for Alzheimer's disease.

PMID- 21074559
TI  - Cerebral arterial gas embolism in swine. Comparison of two sites for air
      injection.
AB  - Cerebral arterial gas embolism is a risk in diving and occurs as a complication
      in surgery and interventional radiology. Swine models for cerebral arterial gas
      embolism have been used in the past. However, injection of air into the main
      artery feeding the pig brain - the ascending pharyngeal artery - might be
      complicated by the presence of the carotid rete, an arteriolar network at the
      base of the brain. On the other hand, anastomoses between external and internal
      carotid territories are present in the pig. In order to determine the most
      appropriate vessel for air injection, we performed experiments in which air was
      injected into either the ascending pharyngeal artery or the external carotid
      artery. We injected 0.25 ml/kg of room air selectively into the ascending
      pharyngeal artery or the external carotid artery of 35-40 kg Landrace pigs (n=8).
      We assessed the effect on cerebral metabolism by measuring intracranial pressure,
      brain oxygen tension and brain glucose and lactate concentrations using cerebral
      microdialysis. Intracranial pressure and brain oxygen tension changed
      significantly in both groups, but did not differ between groups. Brain lactate
      increased significantly more in pigs in which air was injected into the ascending
      pharyngeal artery. Intracranial pressure, brain oxygen tension and brain lactate
      correlated after injection of air into the ascending pharyngeal artery, but not
      after injection into the external carotid artery. Our model is suitable for
      investigation of cerebral arterial gas embolism. The ascending pharyngeal artery
      is the most appropriate vessel for air injection.

PMID- 21074560
TI  - Trial-to-trial noise cancellation of cortical field potentials in awake macaques
      by autoregression model with exogenous input (ARX).
AB  - Gamma band synchronization has drawn increasing interest with respect to its
      potential role in neuronal encoding strategy and behavior in awake, behaving
      animals. However, contamination of these recordings by power line noise can
      confound the analysis and interpretation of cortical local field potential (LFP).
      Existing denoising methods are plagued by inadequate noise reduction,
      inaccuracies, and even introduction of new noise components. To carefully and
      more completely remove such contamination, we propose an automatic method based
      on the concept of adaptive noise cancellation that utilizes the correlative
      features of common noise sources, and implement with AutoRegressive model with
      eXogenous Input (ARX). We apply this technique to both simulated data and LFPs
      recorded in the primary visual cortex of awake macaque monkeys. The analyses here
      demonstrate a greater degree of accurate noise removal than conventional notch
      filters. Our method leaves desired signal intact and does not introduce
      artificial noise components. Application of this method to awake monkey V1
      recordings reveals a significant power increase in the gamma range evoked by
      visual stimulation. Our findings suggest that the ARX denoising procedure will be
      an important pre-processing step in the analysis of large volumes of cortical LFP
      data as well as high frequency (gamma-band related)
      electroencephalography/magnetoencephalography (EEG/MEG) applications, one which
      will help to convincingly dissociate this notorious artifact from gamma-band
      activity.

PMID- 21074562
TI  - Development of a head-mounted, eye-tracking system for dogs.
AB  - Growing interest in canine cognition and visual perception has promoted research
      into the allocation of visual attention during free-viewing tasks in the dog. The
      techniques currently available to study this (i.e. preferential looking) have,
      however, lacked spatial accuracy, permitting only gross judgements of the
      location of the dog's point of gaze and are limited to a laboratory setting. Here
      we describe a mobile, head-mounted, video-based, eye-tracking system and a
      procedure for achieving standardised calibration allowing an output with accuracy
      of 2-3 degrees . The setup allows free movement of dogs; in addition the
      procedure does not involve extensive training skills, and is completely non
      invasive. This apparatus has the potential to allow the study of gaze patterns in
      a variety of research applications and could enhance the study of areas such as
      canine vision, cognition and social interactions.

PMID- 21074561
TI  - Ultrasound-guided needle positioning near the sciatic nerve to elicit compound
      muscle action potentials from the gastrocnemius muscle of the rat.
AB  - The use of ultrasound-guided electrode positioning in near-nerve myography was
      investigated. This is a minimally invasive technique that allows repeated
      measurements to increase accuracy and hence decreases animal numbers. Ultrasound
      imaging of the sciatic nerve was performed in nine rats using a 55 MHz high-end
      transducer. Once visualised, a monopolar needle electrode was placed through the
      skin near this nerve. Upon stimulation, two surface electrodes, placed over the
      gastrocnemius muscle, recorded compound muscle action potentials (CMAPs).
      Reproducibility was tested having two teams of investigators perform the
      recordings consecutively. Reliability of the procedure was determined by
      comparing the ultrasound method to the conventional technique, which requires an
      incision through muscle and skin to expose the sciatic nerve. In all animals the
      sciatic nerve was visible on ultrasound images. Both methods showed CMAP
      latencies (duration was determined as the time interval between the onset latency
      and positive peak). The conventional method had a mean latency of 3.4+/-0.5 ms,
      our method had a mean latency of 3.3+/-0.5 ms. Reproducibility was excellent
      (observed latencies and amplitudes: 3.3 versus 3.3 ms and 25.6+/-5.1 mV versus
      22.5+/-8.8 mV) resulting in a coefficient of variation for duration of 2.1% and
      for amplitude 6.7%. Interclass correlation coefficient was 0.828 for duration.
      Comparing the three different measurements no significant differences were found
      and our new method can therefore be considered reliable and comparable to the
      conventional method. Ultrasound-guided near-nerve needle positioning is a
      reproducible and reliable minimally invasive method for selectively eliciting
      CMAPs, which allows repeated CMAP measurements for studying nerve regeneration in
      rats.

PMID- 21074563
TI  - Directional gene-transfer into the brain by an adenoviral vector tagged with
      magnetic nanoparticles.
AB  - Adenoviral (Ad) vectors are useful for in vivo gene transfer into the brain. If
      Ad vectors are injected into the ventricle of mouse embryonic brain, Ad vectors
      introduce a foreign gene into neural progenitor cells on the surface of
      ventricle. However, Ad vectors were unable to deliver a foreign gene to a
      targeted region of the embryonic brain because Ad vectors evenly infected the
      neural progenitor cells on the surface of ventricle. Therefore, the Ad infection
      to the neural progenitor cells was uncontrollable. To develop a directional gene
      transfer with Ad vector, we generated Ad vector tagged with magnetic
      nanoparticles (Ad-mag) by linking a biotinylated adenovirus vector with a
      streptavidin-conjugated magnetic nanoparticle. Ad-mags were attracted by magnetic
      force in vitro and in vivo. When Ad-mags were injected into the ventricle of
      mouse embryo and a strong magnet was attached to the head of the embryo, Ad-mags
      were attracted to the restricted direction or region where the magnet was placed.
      As a result, Ad-mags efficiently introduced a foreign gene into the restricted
      region of the brain.

PMID- 21074564
TI  - A robust MRI-compatible system to facilitate highly accurate stereotactic
      administration of therapeutic agents to targets within the brain of a large
      animal model.
AB  - Achieving accurate intracranial electrode or catheter placement is critical in
      clinical practice in order to maximise the efficacy of deep brain stimulation and
      drug delivery respectively as well as to minimise side-effects. We have developed
      a highly accurate and robust method for MRI-guided, stereotactic delivery of
      catheters and electrodes to deep target structures in the brain of pigs. This
      study outlines the development of this equipment and animal model. Specifically
      this system enables reliable head immobilisation, acquisition of high-resolution
      MR images, precise co-registration of MRI and stereotactic spaces and overall
      rigidity to facilitate accurate burr hole-generation and catheter implantation.
      To demonstrate the utility of this system, in this study a total of twelve
      catheters were implanted into the putamen of six Large White Landrace pigs. All
      implants were accurately placed into the putamen. Target accuracy had a mean
      Euclidean distance of 0.623 mm (standard deviation of 0.33 mm). This method has
      allowed us to accurately insert fine cannulae, suitable for the administration of
      therapeutic agents by convection-enhanced delivery (CED), into the brain of pigs.
      This study provides summary evidence of a robust system for catheter implantation
      into the brain of a large animal model. We are currently using this stereotactic
      system, implantation procedure and animal model to develop catheter-based drug
      delivery systems that will be translated into human clinical trials, as well as
      to model the distribution of therapeutic agents administered by CED over large
      volumes of brain.

PMID- 21074565
TI  - A simple magnetic separation method for high-yield isolation of pure primary
      microglia.
AB  - Microglial cells play a dynamic role in the brain beyond their established
      function of immune surveillance. Activated microglia play key roles in neural
      development, neuroinflammation, neural repair and neurotoxicity. They are
      particularly important in several neurodegenerative diseases in which sustained
      microglial activation contributes to the progression of neurodegenerative
      processes. Consequently, understanding microglial function in CNS health and
      disease has become an area of active research in recent years. However, a
      significant obstacle to progress in this field has been the inherent difficulties
      in obtaining large amounts of primary microglial cells to routinely perform
      mechanistic studies and characterize signaling pathways regulating the dynamics
      of microglial activation. Herein, we describe a novel column-free magnetic
      separation protocol for high-yield isolation of primary microglia from mouse
      postnatal mixed glial cultures. The procedure is based on optimized culture
      conditions that enable high microglial cell densities in confluent mixed glial
      cultures followed by highly efficient recovery of pure microglia by magnetic
      separation. The novel column-free magnetic separation system utilizes tetrameric
      antibody complexes (TAC) with dual specificity for CD11b-PE labeled microglia and
      dextran magnetic nanoparticles. An FcR blocker (anti-CD16/32) is added to enhance
      the purity of the microglial separation by preventing non-specific labeling of
      other cell types. This procedure yields on average >3*106 microglial cells per
      mouse pup, with a remarkable purity of 97% and recovery of around 87% of
      microglia from the mixed glial population. Importantly, the microglia obtained by
      this method are fully functional and respond like cells obtained by conventional
      isolation techniques.

PMID- 21074566
TI  - Weight loss induced by rimonabant is associated with an altered leptin expression
      and hypothalamic leptin signaling in diet-induced obese mice.
AB  - This study investigates the molecular mechanisms and the center-periphery cross
      talk underlying the anti-obesity effect of the cannabinoid receptor 1 (CB(1))
      antagonist/inverse agonist rimonabant in diet-induced obese (DIO) mice exposed to
      a 31 days chronic treatment with the drug. Present data showed a significant and
      stable weight loss both in animals treated with rimonabant 10mg/kg by oral gavage
      exposed to a high fat diet (SRFD) and in vehicle treated mice switched to a
      regular chow (VEND) with respect to vehicle fat diet fed mice (VEFD). Caloric
      intake was significantly lowered in SRFD and VEND during the first two and four
      days, respectively, then reaching the VEFD consume throughout the treatment. The
      drop of body weight was accompanied by leptin mRNA decrease in visceral fat
      tissue both in VEND and SRFD, as revealed by Real time PCR analysis. No
      difference in CB(1) mRNA receptor expression in hypothalamus and in visceral fat
      tissue among groups was observed. Leptin receptors were decreased in the
      hypothalamus of SRFD but not of VEND mice. Moreover, in SRFD and VEND mice the
      expression of orexigenic genes Neuropeptide Y and Agouti Related Protein (AGRP)
      was increased, while anorexigenic ones, Pro-OpioMelanoCortin (POMC) and Cocaine
      and-Amphetamine-Regulated Transcript (CART) displayed no alteration in any group.
      This data contribute to clarify the molecular basis of the anti-obesity
      properties of rimonabant, underlying the role of the peripheral modulators which
      affect central circuits involved in the regulation of food intake and energy
      homeostasis.

PMID- 21074567
TI  - Contribution of melanin-concentrating hormone (MCH1) receptor to thermoregulation
      and sleep stabilization: evidence from MCH1 (-/-) mice.
AB  - Recent studies have explored the implication of melanin-concentrating hormone
      (MCH) in the process of vigilance states. The current experiments were carried
      out in mice lacking the MCH(1) receptor (-/-) and wild-type (WT) littermates, to
      assess the role of MCH(1) receptor in the regulation of sleep architecture, body
      temperature (BT) and locomotor activity (LMA) under normal condition and
      following a 1h restraint stress at lights onset. Under baseline conditions,
      MCH(1) (-/-) mice exhibited consistent changes in waking and sleeping time across
      the 24-h recording period. We found an increase in the amount of wakefulness
      (MCH(1) (-/-) 680.1 +/- 15.3 min vs. WT, 601.9 +/- 18.1, p<0.05) at the expense
      of total duration of non rapid eye movement (NREM) sleep (MCH(1) (-/-) 664.1 +/-
      13.9 min vs. WT 750.1 +/- 18.5, p<0.05). Additionally, MCH(1) (-/-) mice had a
      higher mean basal body temperature (MCH(1) (-/-), 36.6 +/- 0.1 degrees C vs. WT,
      36.0 +/- 0.1 degrees C, p<0.05), particularly during the light-resting period.
      Restraint stress resulted in an immediate increase in wakefulness with a
      concomitant reduction in NREM sleep and REM sleep in both genotypes, followed by
      a homeostatic rebound sleep. A concomitant long lasting increase in BT,
      independently of the behavioural state accompanied those changes in both
      genotypes. The elevated basal body temperature and reduction in NREM sleep time
      resulting from shorter NREM episode durations observed in MCH(1) (-/-) suggests
      that central MCH(1) receptor has a role in thermoregulation and presumably
      stabilization of NREM sleep.

PMID- 21074568
TI  - A new tool for measuring hand preference in non-human primates: adaptation of
      Bishop's Quantifying Hand Preference task for Olive baboons.
AB  - As non-human primates are phylogenetically close to humans, they are ideal models
      to investigate the precursors of human brain hemispheric specialisation. However,
      in spite of hundreds of reports investigating hand preference, empirically based
      theories generating valuable predictions are still lacking, mainly because of a
      disappointing deficiency in comparability between studies and even more so
      between species. Therefore, we propose here to adapt, for the first time, the
      Quantifying Hand Preference (QHP) task, devised for humans, to non-human
      primates. This test could be a very useful standard measure of hand preference
      for simple reaching in non-human primates because of its simplicity to set up and
      of the parameters (e.g., subject's posture; position of the item) it can control.
      Our test subjects were 42 baboons of various ages and both sexes. Our results
      highlight the crucial influence of item position on hand preference for simple
      reaching, even when the item is positioned close to the subjects' body midline.
      Both sex and age influence baboons' handedness index but this effect varies
      according to the position of the item to be grasped. We discuss our results
      within the theoretical framework concerning hemispheric specialisation for object
      manipulation and with the perspective of replicating this experiment with other
      non-human primate species and genera.

PMID- 21074569
TI  - Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327
      does not prevent acquisition, expression, and extinction of ethanol-seeking
      behavior in mice.
AB  - Although extracellular signal-regulated kinase (ERK) activity is essential for
      the acquisition of a variety of associative learning tasks, its involvement in
      the acquisition and extinction of ethanol (EtOH)-induced conditioned place
      preference (CPP) remains unknown. Therefore, in these experiments we examined the
      effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of
      EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP
      extinction. The parametric findings of Experiment 1 showed that three 30-min (but
      not 15- or 5-min) non-reinforced trials were required to completely extinguish
      EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50mg/kg),
      administered 30 or 90min prior to extinction trials, was unable to impair EtOH
      CPP extinction. Experiment 4 showed that SL327 (50mg/kg) had no effect on
      acquisition of EtOH-CPP or the development of EtOH-induced sensitization during
      conditioning. When administered prior to testing in Experiments 5 and 6, SL327
      did not alter expression of EtOH-CPP but did reduce test activity. Importantly,
      SL327 significantly reduced pERK protein levels when assessed in the dorsal
      striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH
      related learning and EtOH reward in mice, as assessed with CPP, are not impaired
      by the systemically administered MEK-inhibitor SL327.

PMID- 21074570
TI  - Amygdalar orexinergic-GABAergic interactions regulate anxiety behaviors of the
      Syrian golden hamster.
AB  - At present neurobiological interests are directing more attention towards the
      major role of the amygdalar GABA(A) receptor on orexin-dependent behaviors. This
      telencephalic region has been widely studied especially in view of its control on
      various psychiatric disorders such as anxiety and depression. Recently, cross
      talking relationships between these two specific neuroreceptor systems of the
      central-cortical amygdalar complex has been considered an important element for
      anxiety type of behaviors. In the present study, we investigated the effects of
      central amygdalar infusions with orexin-A, orexin-B+/-GABA(A) receptor alpha2
      subunit agonist (flunitrazepam) on elevated plus-maze and light-dark explorative
      behaviors of the facultative hibernating Syrian hamster. In a first case, it
      seemed that doses of orexin administered directly into the central nucleus were
      responsible for greater anxiogenic type of effects as shown by more time being
      spent both in the dark compartment and the closed arm of the elevated plus-maze,
      whereas, these effects were suppressed in the presence of flunitrazepam. At the
      cellular level, the effects of orexin accounted for evident argyrophilic
      reactions (neurodegeneration phenomena) including altered cell membrane and loss
      of cytoplasmic architecture in most amygdalar and hippocampal neuronal fields,
      while in the presence of flunitrazepam these reactions resulted to either be
      unappreciable or absent. Overall the actions of alpha2-dependent inhibitory
      signals tend to corroborate, for the first time, a neuroprotective role against
      the over-excitatory orexinergic neurodegeneration reactions and thus its abnormal
      anxiety-like indications may prove to be therapeutically useful for orexin
      dependent sleeping disorders.

PMID- 21074572
TI  - Diversity of grip in adults and young humans and chimpanzees (Pan troglodytes).
AB  - Grasping is essential for primates in numerous behaviors. A variety of different
      grasping techniques are used for obtaining food. Among humans, several studies
      have shown that the properties of the objects such as the size or the form
      influence grasp patterns. In addition, other works have tested the individual
      variability through grasping strategies and age and several studies have revealed
      some similarities between great apes and humans in grip types. Finally, results
      on hand preference are still equivocal and, for non-human primates, object
      parameters and age effect are rarely tested together, even though it is a
      methodological aspect important to consider. The study sought to determine
      whether grip type varied according to the age of the subject, the species (human
      versus chimpanzee), the size of the object and the hand used. Frame-by-frame
      analysis of hand contact strategies and statistical results indicated that (1)
      adults of both species used fewer contact strategies than juveniles and that
      there was a greater variability of contacts for small than for large objects (2)
      young juvenile chimpanzees and human children follow a similar grip types
      development, i.e. more frequent use of precision grips with age (3) juvenile
      chimpanzees used all five categories of grip and the adults used the "thumb
      fingerpad(s)" more than the "precision grips" in addition to the "power grip" and
      (4) a right hand preference was greater for the grasping of small objects with
      "precision grips" in adults for both species. These results are discussed in
      relationship with neurology, morphology and grasping evolution.

PMID- 21074571
TI  - Nitric oxide synthase inhibitors improve prepulse inhibition responses of Wistar
      rats.
AB  - INTRODUCTION: Cognitive and attentional deficits in schizophrenia include
      impairment of the sensorimotor filter as measured by prepulse inhibition (PPI).
      In this way, the study of animals that naturally present low PPI responses could
      be a useful approach for screening new antipsychotic drugs. Several pieces of
      evidence suggest that dopamine and nitric oxide (NO) can modulate PPI but their
      role in those animals is unknown. OBJECTIVES: The aim of this study was to
      investigate the role of dopamine and NO in Wistar rats with naturally low PPI
      response. METHODS: Male Wistar rats with low PPI responses received an i.p.
      injection of the antipsychotics haloperidol (0.1, 0.3 or 1mg/kg) or clozapine
      (0.5, 1.5 or 5mg/kg), the anxiolytic diazepam (1 or 3mg/kg) or the NO synthase
      (NOS) inhibitors, N(G)- nitro-l-arginine (l-NOARG; 40mg/kg, acutely or sub
      chronically) or 7-Nitroindazole (7-NI; 3, 10 or 30mg/kg). All animals were
      submitted to the PPI test 1h after injection. Striatal and cortical dopamine,
      DOPAC, and noradrenaline levels of rats with low PPI responses were compared to
      rats with normal PPI responses. RESULTS: We found increased levels of
      catecholamines on the striatum and prefrontal cortex of Wistar rats with low PPI.
      In these animals, both antipsychotics, typical and atypical, and NOS inhibitors
      significantly increased PPI. CONCLUSION: Taken together, our findings suggest
      that the low PPI phenotype may be driven by an overactive catecholamine system.
      Additionally, our results corroborate the hypothesis of dopamine and NO
      interaction on PPI modulation and suggest that Wistar rats with low PPI may
      represent an interesting non-pharmacological model to evaluate new potential
      antipsychotics.

PMID- 21074573
TI  - NIH-3T3 fibroblast transplants enhance host regeneration and improve spatial
      learning in ventral subicular lesioned rats.
AB  - Transplants, besides providing neural replacement, also stimulate host
      regeneration, which could serve as a powerful means to establish functional
      recovery in CNS insults. Earlier, we have reported the H3-GFP transplant mediated
      recovery of cognitive functions in the ventral subicular lesioned rats. In the
      present study, we demonstrate the efficacy of a non-neural fibroblast transplants
      in mediating host regeneration and functional recovery in ventral subicular
      lesioned rats. Adult male Wistar rats were lesioned with ibotenic acid in the
      ventral subiculum (VSL) and were transplanted with NIH-3T3 fibroblast cells into
      CA1 region of the hippocampus. Ventral subicular lesioning impaired the spatial
      task performances in rats and produced considerable degree of dendritic atrophy
      of the hippocampal pyramidal neurons. Two months following transplantation, the
      transplants were seen in the dentate gyrus and expressed BDNF and bFGF. Further,
      the VSL rats with fibroblast transplants showed enhanced expression of BDNF in
      the hippocampus and enhanced dendritic branching and increased spine density in
      the CA1 hippocampal pyramidal neurons. Transplantation of fibroblast cells also
      helped to establish functional recovery and the rats with transplants showed
      enhanced spatial learning performances. We attribute the recovery of cognitive
      functions to the graft mediated host regeneration, although the mechanisms of
      functional recovery remain to be elucidated.

PMID- 21074574
TI  - SLV330, a cannabinoid CB(1) receptor antagonist, attenuates ethanol and nicotine
      seeking and improves inhibitory response control in rats.
AB  - Cannabinoid CB(1) receptor (CB(1)R) signaling has been shown to play a role in
      the regulation of addictive behavior. In the present study, our aim was to
      investigate whether the CB(1)R antagonist SLV330 could reduce ethanol and
      nicotine self-administration and cue-induced reinstatement of ethanol and
      nicotine seeking behavior in Wistar rats. In operant chambers, rats were learned
      to emit a specific response (nose poke) in order to receive an ethanol solution
      or intravenous injections of nicotine. Discrete light and tone cues were
      presented during ethanol and nicotine delivery. These cues are particularly
      important for drug self-administration behavior and, through Pavlovian
      conditioning, acquire conditioned reinforcing and motivational properties and are
      therefore able to generate and maintain drug-seeking behavior. Subsequently, the
      CB(1)R antagonist SLV330 (doses ranging from 1 to 10mg/kg, given orally, p.o.)
      was administered to investigate the effects on drug self-administration. In
      addition, responding for ethanol and nicotine was extinguished. Then, the animals
      were tested for cue-induced reinstatement of ethanol and nicotine seeking and
      treated with vehicle or SLV330. Finally, the effects of SLV330 were studied on
      the number of anticipatory responses in the 5-choice serial reaction time task (5
      CSRTT) in order to determine whether this compound could also increase impulse
      control in Wistar rats. The CB(1) antagonist SLV330 was effective in reducing
      ethanol self-administration at a lowest effective dose (LED) of 10mg/kg (p.o.)
      and reinstatement of ethanol seeking at a LED of 3mg/kg (p.o.). SLV330 was also
      effective in reducing nicotine self-administration and reinstatement of nicotine
      seeking, although at a LED of 10mg/kg (p.o.). Finally, SLV330 decreased time
      delay-dependent anticipatory responding (LED of 3.0mg/kg, p.o.), indicating an
      increased inhibitory control. These findings are in agreement with results
      reported with other CB(1) antagonists. The combined action of reducing the
      reinforcing and motivational properties of nicotine and alcohol and the
      improvement of impulse control supports the idea that the cannabinoid system is a
      promising target for anti-relapse medication.

PMID- 21074575
TI  - Inhibition of JNK phosphorylation reverses memory deficit induced by beta-amyloid
      (1-42) associated with decrease of apoptotic factors.
AB  - Alzheimer's disease (AD) is the most common form of dementia that is degenerative
      and terminal disease. The main reason of the disease is still unknown. beta
      amyloid (Abeta) plaques are the important hallmarks of memory impairment in
      patients suffering from AD. Aggregation of these plaques in the hippocampus
      appears during the development of the disease. One of the prominent factors
      having crucial impact in this process is MAPK. JNK, as a member of MAPK family
      has a pivotal role, especially in cell survival. We hypothesized that JNK may
      have beneficial effect on the process of memory improvement. Hence, we performed
      Morris water maze to investigate the possible impact of JNK inhibitor on spatial
      memory in Abeta-injected rats. Our data indicated that intracerebroventricular
      administration of SP600125, a JNK inhibitor, could significantly decrease escape
      latency and increase time spent in target quadrant, in treatment group.
      Furthermore, we evaluated some of the apoptotic factors in the hippocampus of the
      treated rats. Based on our data, the inhibitor led to the significant decrease in
      the amount of caspase-3, TUNEL positive cells, cyclooxygenase-2 and increase in
      Bcl-2/Bax ratio. Given the possible neuroprotective effects of SP600125 on Abeta
      induced memory impairment and apoptosis, our results may open a new avenue for
      the treatment of AD.

PMID- 21074576
TI  - Effects of dilemmas and aromas on performance of the Iowa Gambling Task.
AB  - Males outscore females on the original version of the Iowa Gambling Task (IGT).
      This may be due to differential regional prefrontal cortical activation by males
      and females during the task. PET imagery indicates increased activation in
      dorsolateral (DL) prefrontal cortex (PFC) in males and in medial orbital (ORB)
      PFC in females. A recent study reported that females' scores were elevated to the
      level of males' by having them deliberate moral dilemmas during the IGT. This was
      presumably due to a relative shift in PFC activation from medial ORB PFC to DL
      PFC areas. In the present study, after adding new participants and combining
      results from previous studies we failed to find a significant effect of
      deliberating dilemmas prior to or during the original IGT performance. However,
      the typical gender effect was replicated, as was the females' preference for
      cards from Deck B. The lack of dilemma-enhancement fails to support our previous
      suggestion of increasing activation in DL during the task. However, we
      investigated whether activation of ORB (also secondary olfactory cortex) would
      change IGT performance. When smelling novel aromas during the IGT, males'
      performance was reduced to the level of females whose performance was unchanged.
      This finding suggests that activation of emotional neural substrates might alter
      the dual cognitive (DL)/emotional (ORB) circuits that interact during decision
      making.

PMID- 21074577
TI  - fMRI activation during failures to respond key to understanding performance
      changes with sleep deprivation.
AB  - STUDY OBJECTIVES: During sleep deprivation (SD), failures to respond (FR)
      increase across a variety of tasks. This is the first systematic investigation of
      neural correlates of FR during SD. We use multivariate analysis to model neural
      activation separately for FR and responses (R) at each trial phase. SETTING: In
      two experiments a delayed letter recognition task was performed in a 1.5T scanner
      at 9:30 am after two nights of total SD. Participants were continuously monitored
      in the laboratory. PARTICIPANTS: Healthy young adults from two SD experiments
      (combined n=37; aged 25.55 +/- 3.86 years). MATERIALS AND METHODS: Multivariate
      linear modeling (MLM) was used to find networks of activation that differed
      between FR and R. At each of three trial phases-encoding, retention, and test-two
      networks were expressed. In the encoding phase, the second network was seen
      during FR and was not seen during R. This network constituted widespread
      deactivations (~26,000 voxels) of fronto-parietal and thalamic areas concomitant
      with activation of extrastriate cortex and hippocampus. In a multiple regression
      including activation during FR and R from all networks and all trial phases,
      expression of this encoding-phase network during FR was the key predictor of SD
      related performance impairment, operationalized as greater %FR (eta(p)(2)=0.33),
      lower d' and larger median RT (eta(p)(2)=0.17). CONCLUSIONS: FR were most
      associated with neural disruptions occurring at the encoding phase when subjects
      must attend to and encode items. Further, expression of this FR-related encoding
      phase network made the largest independent contribution to predicting
      vulnerability to overall SD-related impairment.

PMID- 21074578
TI  - Complex I (NADH:ubiquinone oxidoreductase) is active in but non-essential for
      procyclic Trypanosoma brucei.
AB  - The requirement of complex I (NADH:ubiquionone oxidoreductase) for respiration in
      Trypanosoma brucei is controversial. Recent identification of homologues of its
      subunits in mitochondrial proteome resolved a question of its presence or
      absence. However, with one exception, no data have been available concerning the
      function(s) of complex I or its subunits. Here we present a functional RNAi study
      of three (NUBM, NUKM, NUEM) putative subunits of this complex. Although no
      changes were detected in growth, mitochondrial membrane potential or reactive
      oxygen species production in cell lines depleted for target transcript, the NUBM
      and NUKM RNAi knock-downs showed decreased specific NADH:ubiquinone
      oxidoreductase activity. Moreover, glycerol gradients of all cell lines revealed
      the presence of two distinct peaks of NADH dehydrogenase activity, with shifted
      sensitivity to inhibitors of complex I upon RNAi induction. Thus complex I is not
      only present in the procyclic stage of T. brucei 29-13 strain, but it does
      participate in electron transport chain.

PMID- 21074579
TI  - The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes.
AB  - In the mammalian host, the Trypanosoma brucei cell surface is covered with a
      densely packed protein coat of a single protein, the variant surface glycoprotein
      (VSG). The VSG is believed to shield invariant surface proteins from host
      antibodies but there is limited information on how far antibodies can penetrate
      into the VSG monolayer. Here, the VSG surface coat was probed to determine
      whether it acts as a barrier to binding of antibodies to the membrane proximal
      VSG C-terminal domain. The binding of C-terminal domain antibodies to VSG221 or
      VSG118 was compared with antibodies recognising the cognate whole VSGs. The C
      terminal VSG domain was inaccessible to antibodies on live cells but not on fixed
      cells. This provides further evidence that the VSG coat acts as a barrier and
      protects the cell from antibodies that would otherwise bind to some of the other
      externally disposed proteins.

PMID- 21074580
TI  - Three acetylcholinesterases of the pinewood nematode, Bursaphelenchus xylophilus:
      insights into distinct physiological functions.
AB  - Acetylcholinesterase (AChE) plays a key role in postsynaptic transmission in most
      animals. Nematodes encode multiple AChEs, implying its functional diversity. To
      explore physiological functions of multiple AChEs, three distinct AChEs (BxACE-1,
      BxACE-2, and BxACE-3) were identified and characterized from the pinewood
      nematode. Sequencing comparison with Torpedo AChE and Caenorhabditis elegans ACEs
      identified choline-binding site, catalytic triad functional site, three internal
      disulfide bonds and aromatic residues for the catalytic gorge. Transcriptional
      profiling by quantitative real-time PCR revealed that BxACE-3 is more actively
      transcribed than BxACE-1 (2-3 times) and BxACE-2 (9-18 times) in both propagative
      and dispersal stages. The three BxACEs were functionally expressed using
      baculovirus system. Kinetic analysis of in vitro-expressed BxACEs revealed that
      the substrate specificity was highest in BxACE-1 whereas the catalytic efficiency
      was highest in BxACE-2. In inhibition assay, BxACE-3 showed the lowest inhibition
      rate. Taken together, it appears that both BxACE-1 and BxACE-2 play common but
      non-overlapping roles in synaptic transmission, whereas BxACE-3 may have non
      neuronal functions. The current findings should provide valuable insights into
      the evolutionary process and various physiological roles of AChE.

PMID- 21074581
TI  - Hydrogenosome-localization of arginine deiminase in Trichomonas vaginalis.
AB  - The arginine dihydrolase (ADH) pathway has an analogous function to the urea
      cycle in mitochondria-containing cells, by removing nitrogen from amino acids and
      generating ATP. Subcellular localization of the ADH pathway enzymes in
      Trichomonas vaginalis revealed that arginine deiminase (ADI) localizes to the
      hydrogenosome, a mitochondrion-like organelle of anaerobic protists. However the
      other enzymes of the ADH pathway, ornithine carbamyltransferase and carbamate
      kinase localize to the cytosol. Three gene sequences of T. vaginalis ADI (ADI 1
      3) were identified in the T. vaginalis genome, all having putative mitochondrial
      targeting sequences. The ADI sequences were cloned and used to probe T. vaginalis
      using a carboxyterminal di-hemogglutinin epitope tag which demonstrated co
      localization with malic enzyme confirming the hydrogenosome localization of this
      enzyme.

PMID- 21074582
TI  - EMG activity in response to static and dynamic facial expressions.
AB  - The EMG activity associated with static and dynamic facial expressions (morphs
      with happy or angry emotions) were compared. We hypothesized that dynamic faces
      would (a) enhance facial muscular reactions and (b) evoke higher intensity
      ratings. Our analysis showed that dynamic expressions were rated as more intense
      than static ones. Subjects reacted spontaneously and rapidly to happy faces with
      increased zygomaticus major EMG activity and decrease corrugator supercilii EMG
      activity - showing greater changes in response to dynamic than to static stimuli
      in both muscles. In contrast, angry faces evoked no alteration of EMG activity in
      zygomaticus muscles and only small changes in the corrugator muscle EMG, and
      there was no difference between the responses to static and dynamic stimuli. It
      may be concluded that the dynamic property facilitates processing of facial
      expressions of emotions.

PMID- 21074583
TI  - The role of the dorsolateral prefrontal cortex in deception when remembering
      neutral and emotional events.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the neural
      correlates of deception while remembering neutral events and emotional events.
      Before fMRI, subjects were presented with a series of neutral and emotional
      pictures and were asked to rate each picture for arousal. During fMRI, subjects
      were presented with the studied and nonstudied pictures and were asked to make an
      honest recognition judgment in response to half of the pictures and a dishonest
      response to the remaining half. We found that deception pertaining to the memory
      of neutral pictures was associated with increased activity in the bilateral
      dorsolateral prefrontal cortex, the left ventrolateral prefrontal cortex, and the
      left orbitofrontal cortex. We also found that deception while remembering
      emotional pictures was associated with increased activity in the bilateral
      dorsolateral prefrontal cortex. An overlapping activation between the two types
      of deception was found in the bilateral dorsolateral prefrontal cortex. Our
      results indicate that the dorsolateral prefrontal cortex is associated with the
      executive aspects of deception, regardless of the emotional valence of memory
      content.

PMID- 21074584
TI  - Regulation of the expression of the varicella-zoster virus open reading frame 66
      gene.
AB  - The varicella-zoster virus (VZV) open reading frame (ORF) 66 encodes a
      serine/threonine kinase that phosphorylates the major viral transactivator
      protein, immediate-early (IE) 62, preventing its nuclear importation. Cytoplasmic
      sequestration of IE62 may alter viral gene transcription and could serve as a
      mechanism for maintaining VZV latency. We examined the regulation of expression
      of the ORF66 gene by mapping the promoter region, which was localized to within
      150 bases of the start codon. The ORF66 promoter was activated by two viral
      regulatory proteins, IE62 and IE63. We evaluated the binding of viral regulatory
      proteins and cellular transcription factors based on recognized cellular
      transcription factor binding sites identified within the ORF66 promoter. These
      included Sp1 and TBP binding sites, several of which were essential for optimal
      promoter activity. Site-directed mutations in Sp1 and TBP binding sites led to
      varying degrees of impairment of ORF66 gene expression in the context of VZV
      infection. We also examined the effect of Sp1 and TBP mutations on IE62, Sp1, and
      TBP binding. These studies reveal that host cell-derived and viral factors
      contribute to and cooperate in the expression of this important viral kinase
      gene.

PMID- 21074585
TI  - Evaluation of polyanion-coated biodegradable polymeric micelles as drug delivery
      vehicles.
AB  - Polymeric micelles, as drug delivery vehicles, must achieve specific targeting
      and high stability in the body for efficient drug delivery. We recently reported
      the preparation of polyanion-coated biodegradable polymeric micelles by coating
      positively charged polymeric micelles consisting of poly(L-lysine)-block-poly(L
      lactide) (PLys-b-PLLA) AB diblock copolymers with anionic hyaluronic acid (HA) by
      polyion complex (PIC) formation. The obtained HA-coated micelles showed
      significantly higher stability in aqueous solution. In this study, to evaluate
      the HA-coated polymeric micelles as a drug carrier, model drug release from the
      micelles and cytotoxicity of the micelles were investigated. The HA-coated
      micelles showed sustained release of model drugs and low cytotoxicity. It is
      known that there are receptors for HA on liver sinusoidal endothelial cells
      (LSEC). Specific interactions of HA-coated micelles with LSECs and Kupffer cells
      were investigated and compared with polymeric micelles coated with other
      polyanionic polysaccharides, i.e., heparin (Hep) and carboxymethyl-dextran
      (CMDex). Although Hep-coated micelles and CMDex-coated micelles were incorporated
      into both Kupffer cells and LSECs, HA-coated micelles were taken up only into
      LSECs. These results suggest HA-coated micelles have potential utility as drug
      delivery vehicles exhibiting specific accumulation into LSECs.

PMID- 21074586
TI  - Ophthalmic delivery of cyclosporine A by punctal plugs.
AB  - Dry eyes are treated by instillation of eye drops of cyclosporine A emulsion or
      by punctal plug insertion in canaliculus to block tear drainage. This paper
      focuses on a novel approach of developing a punctal plug that can also release
      cyclosporine A to provide a dual mechanism for treating dry eyes. The punctal
      plug consists of a cylindrical hydroxy ethyl methacrylate core containing drug
      microparticles surrounded by an impermeable silicone shell that covers about 50%
      of the core, with the uncovered part directed towards the eyes. The geometry of
      this design is significantly different from those in patent literature, which are
      mostly designed to be rods. Plugs release cyclosporine A for a period of about 3
      months at zero-order at a rate of about 3 MUg/day. The in vivo release rates are
      expected to be about half of this value. A mathematical model is presented that
      provides an accurate estimate of the release without any fitting parameter.
      Pharmacokinetic models are also developed for drug delivered through Restasis(r)
      and punctal plugs, and based on these models the release rate of about 1.5
      MUg/day may be therapeutically effective. The predictions of the ocular
      pharmacokinetic model are in reasonable agreement with reported measurements in
      humans.

PMID- 21074587
TI  - Time-dependent contribution of non neuronal cells to BDNF production after
      ischemic stroke in rats.
AB  - Although brain-derived neurotrophic factor (BDNF) plays a central role in
      recovery after cerebral ischemia, little is known about cells involved in BDNF
      production after stroke. The present study testes the hypothesis that neurons are
      not the unique source of neosynthesized BDNF after stroke and that non neuronal
      BDNF producing cells differ according to the delay after stroke induction. For
      this purpose, cellular localization of BDNF and BDNF content of each hemisphere
      were analysed in parallel before and after (4h, 24h and 8d) ischemic stroke in
      rats. Stroke of different severities was induced by embolization of the brain
      with variable number of calibrated microspheres allowing us to explore the
      association between BDNF production and neuronal death severity. The main results
      are that (a) unilateral stroke increased BDNF production in both hemispheres with
      a more intense and long-lasting effect in the lesioned hemisphere, (b) BDNF
      levels either of the lesioned or unlesioned hemispheres were not inversely
      correlated to neuronal death severity whatever the delay after stroke onset, (c)
      in the unlesioned hemisphere, stroke resulted in increased BDNF staining in
      neurons and ependymal cells (at 4h and 24h), (d) in the lesioned hemisphere,
      beside neurons and ependymal cells, microglial cells (at 24h), endothelial cells
      of cerebral arterioles (at 4h and 24h) and astrocytes (at 8d) exhibited a robust
      BDNF staining as well. Taken together, overall data suggest that non neuronal
      cells are able to produce substantial amount of BDNF after ischemic stroke and
      that more attention should be given to these cells in the design of strategies
      aimed at improving stroke recovery through BDNF-related mechanisms.

PMID- 21074588
TI  - Cannabinoid receptor 1 induces a biphasic ERK activation via multiprotein
      signaling complex formation of proximal kinases PKCepsilon, Src, and Fyn in
      primary neurons.
AB  - Cannabinoid receptors 1 (CB1Rs) play important roles in the regulation of
      dendritic branching, synapse density, and synaptic transmission through multiple
      G-protein-coupled signaling systems, including the activation of the
      extracellular signal-regulated kinases ERK1/2. The proximal signaling
      interactions leading to ERK1/2 activation by CB1R in CNS remain, however,
      unclear. Here, we present evidence that the CB1R agonist methanandamide induced a
      biphasic and sustained activation of ERK1/2 in primary neurons derived from E7
      telencephalon. We show that E7 neurons natively express high levels of CB1R
      message and protein, the majority of which associates with PKCE at basal
      conditions. We now demonstrate that the first peak of ERK activation by CB1R was
      mediated by the sequential activation of G(q), PLC, and PKCE, selectively, and
      that the CB1R-activated PKCE acutely formed transient signaling modules
      containing activated Src and Fyn. A second pool of CB1Rs, coupled to PTX
      sensitive activation of G(i/o), utilized as effectors additional Src and Fyn
      molecules to generate a second, additional wave of ERK activation at 15 min.
      Concurrently to these intermolecular signaling interactions, cytoskeleton
      associated proteins MARCKS and p120catenin were drastically modified by
      phosphorylation of PKC and Src, respectively. These receptor-proximal signaling
      events correlated well with induction of neuritic outgrowth in the long term. Our
      data provide evidence for multiprotein signaling complex formation in the
      coupling of CB1R to activation of ERK in CNS neurons, and may elucidate several
      of the less understood acute effects of cannabinoid drugs.

PMID- 21074589
TI  - Comparative neurochemical profile of 3,4-methylenedioxymethamphetamine and its
      metabolite alpha-methyldopamine on key targets of MDMA neurotoxicity.
AB  - The neurotoxicity of MDMA or "Ecstasy" in rats is selectively serotonergic, while
      in mice it is both dopaminergic and serotonergic. MDMA metabolism may play a key
      role in this neurotoxicity. The function of serotonin and dopamine transporter
      and the effect of MDMA and its metabolites on them are essential to understand
      MDMA neurotoxicity. The aim of the present study was to investigate and compare
      the effects of MDMA and its metabolite alpha-methyldopamine (MeDA) on several
      molecular targets, mainly the dopamine and serotonin transporter functionality,
      to provide evidence for the role of this metabolite in the neurotoxicity of MDMA
      in rodents. MeDA had no affinity for the serotonin transporter but competed with
      serotonin for its uptake. It had no persistent effects on the functionalism of
      the serotonin transporter, in contrast to the effect of MDMA. Moreover, MeDA
      inhibited the uptake of dopamine into the serotonergic terminal and also MAO(B)
      activity. MeDA inhibited dopamine uptake with a lower IC(50) value than MDMA.
      After drug washout, the inhibition by MeDA persisted while that of MDMA was
      significantly reduced. The effect of MDMA on the dopamine transporter is related
      with dopamine release from vesicular stores, as this inhibition disappeared in
      reserpine-treated animals. However, the effect of MeDA seems to be a persistent
      conformational change of this transporter. Moreover, in contrast with MDMA, MeDA
      did not show affinity for nicotinic receptors, so no effects of MeDA derived from
      these interactions can be expected. The metabolite reduced cell viability at
      lower concentrations than MDMA. Apoptosis plays a key role in MDMA induced
      cellular toxicity but necrosis is the major process involved in MeDA
      cytotoxicity. We conclude that MeDA could protect against the serotonergic lesion
      induced by MDMA but potentiate the dopaminergic lesion as a result of the
      persistent blockade of the dopamine transporter induced this metabolite.

PMID- 21074591
TI  - Determination of trace metals in canned anchovies and canned rainbow trouts.
AB  - Trace metal (Fe, Zn, Cu, Cd, Sn, Hg and Pb) concentrations of canned anchovies
      (Engraulis encrasicolus Linnaeus, 1758) and canned rainbow trouts (Oncorhynchus
      mykiss Walbaum, 1792), commercialized in Turkey, were determined using
      Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). The average contents of
      trace metals in canned anchovies and canned rainbow trouts were found as 50.708
      and 6.980 mg/kg for iron, 22.467 and 11.605 mg/kg for zinc, 1.145 and 0.541 mg/kg
      for copper, 0.019 and 0.001 mg/kg for cadmium, 0.140 and 0.023 mg/kg for tin,
      0.041 and 0.026 mg/kg for mercury, and 0.188 and 0.167 mg/kg for lead,
      respectively. Although these products pose no risk with respect to the
      concentrations of zinc, copper, cadmium, tin and mercury, some of the samples had
      higher contents of lead and iron than the permissible limits. Comprehensive and
      periodic controls of trace metals in canned fish are needed to assess the safety
      of these products with respect to human health.

PMID- 21074590
TI  - Some consequences of using cigarette machine smoking regimes with different
      intensities on smoke yields and their variability.
AB  - When smoking cigarettes under an intense regime with a combination of 100%
      ventilation blocking and high flow rates, as currently mandated by Health Canada,
      significant increases in filter temperatures and disproportionately high levels
      of mainstream smoke water and moisture accumulating in the spent filter were
      found when compared to other smoking regimes, especially for highly filter
      ventilated cigarettes. These effects have been reported to decrease cigarette
      firmness during the course of smoking, to alter filtration properties and
      efficiencies and to confound the measurement of particulate matter. The high
      filter temperatures generated also lead to significant amounts of vapour phase
      compounds desorbing from carbon filters and an over-estimation of the yields of
      these components. Less adsorption on or more desorption from carbon filters was
      found for compounds with the highest volatility. Therefore, yield data from the
      intense regime may not reflect the effectiveness of cigarette design features to
      reduce certain smoke components that occurs when products are smoked under
      conditions closer to those used by the majority of smokers in real world
      situations. In addition, a combination of these interacting factors may explain
      the worse level of between-laboratory reproducibility data for particulate matter
      measurement obtained during intense machine smoking. Among-laboratory data
      variability for vapour phase components, other than carbon monoxide, and for
      particulate phase components, other than nicotine, still needs to be evaluated in
      collaborative studies. Before proposing smoking regimes as tools to evaluate
      smoke emissions, it is essential to understand these various interacting factors
      and subsequent uncontrolled effects that such regimes can generate and the
      limitations of their use. These observations imply that higher tolerances may
      need to be set and taken into account when smoking under the intense regime
      before deciding that, for a given product, there are real differences between the
      yields determined in different laboratories.

PMID- 21074592
TI  - Plants with genetically modified events combined by conventional breeding: an
      assessment of the need for additional regulatory data.
AB  - Crop varieties with multiple GM events combined by conventional breeding have
      become important in global agriculture. The regulatory requirements in different
      countries for such products vary considerably, placing an additional burden on
      regulatory agencies in countries where the submission of additional data is
      required and delaying the introduction of innovative products to meet
      agricultural needs. The process of conventional plant breeding has predictably
      provided safe food and feed products both historically and in the modern era of
      plant breeding. Thus, previously approved GM events that have been combined by
      conventional plant breeding and contain GM traits that are not likely to interact
      in a manner affecting safety should be considered to be as safe as their
      conventional counterparts. Such combined GM event crop varieties should require
      little, if any, additional regulatory data to meet regulatory requirements.

PMID- 21074593
TI  - Strategies for elimination of cyanogens from cassava for reducing toxicity and
      improving food safety.
AB  - Toxicity of cassava arises due to the presence of the cyanoglucosides linamarin
      and lotaustralin which are hydrolysed by endogenous enzyme linamarase to
      acetonecyanohydrin (ACN) and cyanide (CN) which are toxic. Major research efforts
      to eliminate/reduce cyanoglucosides have focused on (i) development of
      acyanogenic cassava varieties by breeding; (ii) controlling its metabolism; and
      (iii) processing to remove cyanogens. The cyanoglucoside (CNG) content in cassava
      is genetically controlled and cultivars may be classified as low (<50 MUg/g),
      medium (50-100 MUg/g) and high CN (>100 MUg CN eq./g) varieties. Molecular
      techniques for reducing tuber CNG have focused on development of transgenic
      plants with reduced expression of cyt P 450 in leaves, or increased expression of
      hydroxynitrilelyase in tuber. For immediate solution, CNG content can be reduced
      using several processing methods. Traditional methods used for processing include
      boiling, drying, parboiling and drying, baking, steaming, frying and preparation
      of flour. These processes result in CN losses ranging from 25% to 98%. The
      cyanogen level in the final product is influenced both by the tuber CNG and the
      method of processing. In order to achieve safe levels of 10 MUg/g in cassava
      products, new methods of processing, especially for cassava containing more than
      250 MUg CN eq./g, remains a challenging problem.

PMID- 21074594
TI  - Risk assessment of streptomycin and tetracycline residues in meat and milk on
      Croatian market.
AB  - In addition to biological hazards like bacteria, viruses, parasites, the
      occurrence of chemical hazards is another characteristic of modern food
      production. The use of veterinary medicines in intensive production of animals is
      conditio sine qua non so it is impossible to avoid in full the presence of their
      residues in food. This paper presents quantitative risk assessment of
      streptomycin and tetracycline based on acceptable daily intake, daily consumption
      of milk and meat in Croatia (0.222 and 0.126 kg/person, respectively) and
      residues of these two veterinary drugs in this type of food. The median value for
      streptomycin in milk and meat was 11.50 and 38.00 MUg/kg, respectively (milk:
      average: 15.57 MUg/kg; range from 0 to 73.82 MUg/kg; meat: average 44.14 MUg/kg;
      range from 0 to 278.35 MUg/kg). The median value for tetracycline in milk and
      meat was 1.50 MUg/kg (milk: average 1.5 MUg/kg; range, from 0 to 4.26 MUg/kg;
      meat: average 1.62 MUg/kg; range from 0 to 5.35 MUg/kg). Based on the median
      value it can be concluded that the estimated daily intake of streptomycin and
      tetracycline through milk and meat in Croatia is low (streptomycin: 7.33
      MUg/person/day; tetracycline: 0.52 MUg/person/day), and the risk is assessed as
      negligible.

PMID- 21074595
TI  - Poorly soluble particulates: searching for a unifying denominator of
      nanoparticles and fine particles for DNEL estimation.
AB  - Under the new European chemicals regulation, REACH (Registration, Evaluation,
      Authorization and Restriction of Chemicals) a Derived No-Effect Level (DNEL),
      i.e., the level of exposure above which humans should not be exposed, is defined.
      The focus of this paper is to develop a weight-of-evidence-based DNEL-approach
      for inhaled poorly soluble particles. Despite the common mode of action of
      inhaled insoluble, spherical particulate matter (PM), a unifying, most
      appropriate metric conferring pulmonary biopersistence and toxicity has yet not
      been demonstrated. Nonetheless, there is compelling evidence from repeated rat
      inhalation exposure studies suggesting that the particle displacement volume is
      the most prominent unifying denominator linking the pulmonary retained dose with
      toxicity. Procedures were developed to analyze and model the pulmonary
      toxicokinetics from short-term to long-term exposure. Six different types of
      poorly soluble nano- to submicron PMs were compared: ultrafine and pigmentary
      TiO2, synthetic iron oxide (Fe3O4, magnetite), two aluminum oxyhydroxides (AlOOH,
      Boehmite) with primary isometric particles approximately of either 10 or 40 nm,
      and MWCNT. The specific agglomerate densities of these materials ranged from 0.1
      g/cm3 (MWCNT) to 5 g/cm3 (Fe3O4). Along with all PM, due to their long retention
      half-times and associated biopersistence in the lung, even short-term inhalation
      studies may require postexposure periods of at least 3 months to reveal PM
      specific dispositional and toxicological characteristics. This analysis provides
      strong evidence that pulmonary toxicity (sustained inflammation) is dependent on
      the volume-based cumulative lung exposure dose. Lung toxicity, evidenced by PMN
      in BAL occurred at lung doses exceeding 10-times the overload threshold.
      Furthermore, the conclusion is supported that repeated inhalation studies on rats
      should utilize an experimental window of cumulative volume loads of respirable PM
      in the range of 1 MUl/lung (no-adverse-effect range); however, not exceeding ~10
      MUl/lung that would lead to retention half-times increasing 1 year. This can be
      targeted best by computational toxicology, i.e., the modeling of particle
      deposition and lung retention biokinetics during the exposure and recovery
      periods. Inhalation studies exceeding that threshold volume may lead to
      meaningless findings difficult to extrapolate to any real-life scenario. In
      summary, this analysis supports a volume-based generic mass concentration of 0.5
      MUl PM(respirable)/m3 x agglomerate density, independent on nano- or submicron
      sized properties, as a generic no-adverse effect level in both rats and humans.

PMID- 21074596
TI  - Latex allergy and filaggrin null mutations.
AB  - OBJECTIVES: Natural rubber latex (NRL) contains over 200 proteins of which 13
      have been identified as allergens and the cause of type I latex allergy. Health
      care workers share a high occupational risk for developing latex allergy.
      Filaggrin null mutations increase the risk of type I sensitizations to
      aeroallergens and it is possible that filaggrin null mutations also increase the
      risk of latex allergy. The aim of this paper was to examine the association
      between filaggrin null mutations and type I latex allergy. METHODS: Twenty latex
      allergic and 24 non-latex allergic dentists and dental assistants, occupationally
      exposed to latex, were genotyped for filaggrin null mutations R501X and 2282del4.
      Latex allergy was determined by a positive reaction or a historical positive
      reaction to a skin prick test with NRL. RESULTS: 41 individuals were successfully
      genotyped. Three individuals were filaggrin mutation carriers. One (2.4%) was a
      2282del4 heterozygote and two (4.9%) were R501X heterozygote. No homozygote or
      compound heterozygote carriers were detected. No association between filaggrin
      null mutations and type I latex allergy was found (p=0.24). Patients with type I
      latex allergy more often reported contact dermatitis. CONCLUSIONS: This is the
      first study to examine a highly plausible association between filaggrin null
      mutations and type I latex allergy. The study subjects were occupationally
      exposed to latex but no association between latex allergy and filaggrin mutations
      were detected. Sensitization to latex in the cases in this study may not have
      occurred through direct skin contact but through the respiratory organs via latex
      proteins that are absorbed in glove powder and aerosolized.

PMID- 21074598
TI  - Doxorubicin-induced central nervous system toxicity and protection by xanthone
      derivative of Garcinia mangostana.
AB  - Doxorubicin (Dox) is a potent, broad-spectrum chemotherapeutic drug used around
      the world. Despite its effectiveness, it has a wide range of toxic side effects,
      many of which most likely result from its inherent pro-oxidant activity. It has
      been reported that Dox has toxic effects on normal tissues, including brain
      tissue. The present study tested the protective effect of a xanthone derivative
      of Garcinia Mangostana against Dox-induced neuronal toxicity. Xanthone can
      prevent Dox from causing mononuclear cells to increase the level of tumor
      necrosis factor-alpha (TNFalpha). We show that xanthone given to mice before Dox
      administration suppresses protein carbonyl, nitrotyrosine and 4-hydroxy-2'
      nonenal (4HNE)-adducted proteins in brain tissue. The levels of the pro-apoptotic
      proteins p53 and Bax and the anti-apoptotic protein Bcl-xL were significantly
      increased in Dox-treated mice compared with the control group. Consistent with
      the increase of apoptotic markers, the levels of caspase-3 activity and TUNEL
      positive cells were also increased in Dox-treated mice. Pretreatment with
      xanthone suppressed Dox-induced increases in all indicators of injury tested.
      Together, the results suggest that xanthone prevents Dox-induced central nervous
      system toxicity, at least in part, by suppression of Dox-mediated increases in
      circulating TNFalpha. Thus, xanthone is a good candidate for prevention of
      systemic effects resulting from reactive oxygen generating anticancer
      therapeutics.

PMID- 21074599
TI  - Pre-treatment of adrenomedullin suppresses cerebral edema caused by transient
      focal cerebral ischemia in rats detected by magnetic resonance imaging.
AB  - Recent studies suggest the protective effects of adrenomedullin (AM) on ischemic
      brain damage. The present study was aimed at investigating the effects of AM and
      its receptor antagonist, AM22-52, on ischemia-induced cerebral edema and brain
      swelling in rats using magnetic resonance imaging. Rats were subjected to 60 min
      of middle cerebral artery occlusion (MCAO) followed by reperfusion. Intravenous
      injection of AM (1.0 MUg/kg), AM22-52 (1.0 MUg/kg), or saline was made before
      MCAO. Effects of AM injection just after reperfusion were also investigated. One
      day after ischemia, increases in T2-weighted signals in the brain were clearly
      observed. Total edema volume, as well as brain swelling, was greatly and
      significantly reduced by pre-treatment of AM (reduced by 53%). Extent of brain
      swelling was significantly correlated with the volume of cerebral edema. The
      protective effect of AM against edema was more clearly observed in the cerebral
      cortex (reduced by 63%) than the striatum (reduced by 31%). Increased T2
      relaxation time in the cortex was recovered partially by pre-treatment of AM.
      Post-treatment of AM had no effects. Pre-treatment of AM22-52 tended to
      exacerbate the edema. In another line of experiment, cocktail administration of
      AM with melatonin, a pineal product having neuroprotective potential as a free
      radical scavenger, failed to enhance the protective effects of AM alone. The
      present study clearly suggests the prophylactic effects of AM against cerebral
      edema, especially the cortical edema, in a rat stroke model.

PMID- 21074600
TI  - Differentially abundant transcripts in PBMC of hospitalized geriatric patients
      with hip fracture compared to healthy aged controls.
AB  - The abundance of a selection of transcript species involved in inflammation,
      immunosenescence and stress response was compared between PBMC of 35 geriatric
      patients with hip fracture in acute phase (days 2-4 after hospitalization) or
      convalescence phase (days 7-10) and 28 healthy aged controls. Twenty-nine
      differentially abundant transcripts were identified in acute phase versus healthy
      ageing. Twelve of these transcripts remained differentially abundant in
      convalescence phase, and 22 were similarly differentially abundant in acute phase
      of geriatric infectious diseases. Seven of these 22 transcripts were previously
      identified as differentially abundant in PBMC of healthy aged versus healthy
      young controls, with further alteration for CD28, CD69, LCK, CTSD, HMOX1, and
      TNFRSF1A in acute phase after geriatric hip fracture and infectious diseases. The
      next question is whether these alterations are common to other geriatric diseases
      and/or preexist before the clinical onset of the diseases.

PMID- 21074601
TI  - EGF signaling comes of age: promotion of healthy aging in C. elegans.
AB  - More than 400 genes have been noted to modulate Caenorhabditis elegans longevity.
      Recent studies testing the role of proposed secreted insulin-binding proteins
      unexpectedly revealed a potent role for the EGF signaling pathway in promoting
      healthy aging and longevity in C. elegans. Activation of EGF receptor LET-23 is
      associated with increased mean and maximum lifespan, maintained pharyngeal
      pumping, extended locomotory function, and low lipofuscin and advanced glycation
      end product accumulation. Conversely, reducing the activity of the EGF pathway is
      associated with system-wide evidence of progeria. The EGF pathway appears to work
      in a manner largely independent of the insulin/IGF-like pathway, in that effects
      are additive with reduction of DAF-2/InsR activity and are not affected by DAF
      16/FOXO transcription factor deficiency. Two novel regulators of EGF signaling,
      called HPA-1 and HPA-2 (for the high performance in advanced age locomotory
      phenotypes that their disruption confers), negatively regulate EGF action,
      possibly by binding and sequestering EGF. Interestingly, whereas HPA-1 appears to
      control aging of the animal overall, HPA-2 exerts an effect primarily on
      locomotory aging. As such, HPA-2 is an example of a protein with an effect on
      healthspan but not lifespan, a gene class that may have been missed in screens
      focused on longevity endpoint. To date, roles for EGF signaling in adult
      maintenance (particularly in non-dividing tissues) have not been addressed in
      other organisms-should EGF signaling exert a conserved impact on healthy aging,
      testing this hypothesis could hold implications for anti-aging therapies.

PMID- 21074602
TI  - Delayed puberty in prenatally glucocorticoid administered female rats occurs
      independently of the hypothalamic Kiss1-Kiss1r-GnRH system.
AB  - Intrauterine growth retardation (IUGR) is an important risk factor for the
      pathogenesis of diseases after birth. Long-lasting alterations in the structure
      and function of tissues and the neuroendocrine system, which are known as
      'programming effects', increase the risks of these diseases. To investigate the
      pathophysiology of programming effects, several kinds of IUGR rodent models have
      been used in experiments. Sexual maturation and the onset of puberty are delayed
      in these models. We have previously reported that decreased action of
      hypothalamic kisspeptin, which is a positive regulator of GnRH, contributes to
      the delayed onset of puberty in undernutrition-induced IUGR rats. The aim of this
      study was to evaluate whether the hypothalamic Kiss1-Kiss1r-GnRH system is also
      altered in dexamethasone-induced IUGR rats. Compared with offspring from an
      untreated mother (control), offspring from a dexamethasone administered mother
      (DEX) showed a significant reduction in body weight throughout the experimental
      period (from birth to the prepubertal period) and the delayed onset of puberty.
      There were no significant differences between the control and DEX groups with
      regard to their hypothalamic Kiss1, Kiss1r, GnRH, CRH, NPY and POMC mRNA levels
      during the experimental period or their serum LH, FSH, or leptin concentrations
      at postnatal day 28 or vaginal opening (VO). Compared with the control, DEX
      showed significantly lower ovarian weight at postnatal day 28, but not at VO.
      These results suggested that the delayed onset of puberty induced by maternal
      dexamethasone administration would occur independently of hypothalamic Kiss1
      Kiss1r-GnRH system.

PMID- 21074603
TI  - Effect of acute and chronic arsenic exposure on growth, structure and virulence
      of Aeromonas hydrophila isolated from fish.
AB  - Aeromonas hydrophila being a ubiquitous bacterium is prone to arsenic exposure.
      The present study was designed to determine the role of arsenic on growth and
      virulence of A. hydrophila. Exposure to arsenic (1 mg L(-1) and 2 mg L(-1)) had
      no effect on growth but significantly inhibited the hemolytic and cytotoxic
      potential of exposed bacteria. Transmission electron microscopy revealed loss of
      membrane integrity and presence of condensed cytoplasm suggestive of acute stress
      in bacteria exposed to arsenic. Arsenic-adapted bacteria were developed by
      repeated sub-culturing in presence of arsenic. Arsenic-adaptation led to
      significant recovery in hemolytic and cytotoxic potential. The arsenic-adapted
      bacteria exhibited normal membrane integrity, decreased cytoplasmic condensation
      and possessed scattered polysome like structures in the cytoplasm. A positive
      correlation was observed between arsenic tolerance and resistance to several
      antimicrobials. Arsenic-adaptation failed to confer cross-protection to mercury
      and cadmium stress. SDS-PAGE analysis revealed the expression of two new proteins
      of approximately 85 kDa and 79 kDa respectively in arsenic-adapted A. hydrophila.
      Plasmid-curing and transformation studies clearly indicate plasmid has no role on
      arsenic resistance trait of the bacteria. Our study, for the first time, reports
      a structure and function relationship of xenobiotics on bacteria.

PMID- 21074604
TI  - Tissue expression of steroid hormone receptors is associated with differential
      immune responsiveness.
AB  - Glucocorticoids have been used as treatments against a number of diseases,
      especially autoimmune/inflammatory conditions in which the immune system is
      overactive. These treatments have varying degrees of responsiveness among
      individuals and in different tissues (including brain); therefore, it is
      important to determine what could account for these differences. In this study,
      we evaluated expression of stress hormone receptors in immune cells from lymphoid
      and non-lymphoid tissues (including brain) as a possible explanation. We analyzed
      leukocytes (CD45(+)) in kidney, liver, spleen, and thymus tissues from healthy
      mice for expression of the receptor for stress hormone (glucocorticoid-GR) as
      well as other steroid hormones (androgen-AR, progesterone-PR) and found that all
      tissues expressed these steroid hormone receptors but with varying patterns. To
      determine whether tissue-specific differences were related to immune cell
      composition, we examined steroid hormone receptor expression in T lymphocytes
      from each of these tissues and found similar patterns of expression in these
      cells regardless of tissue source. Because glucocorticoids can also impact brain
      function, we further examined expression of the stress hormone receptor in brain
      tissue and found GR expressed in immune cells at this site. In order to
      investigate the potential impact in an area of neuropathology, we utilized a
      mouse model of West Nile Virus (WNV). We observed pathological changes in brains
      of WNV-infected animals and T lymphocytes in the areas of inflammation; however,
      these cells did not express GR. These data indicate that tissue-specific
      differences in steroid hormone receptor expression by immune cells could
      determine responsiveness to steroid hormone treatment.

PMID- 21074606
TI  - TNFR1 is essential for CD40, but not for lipopolysaccharide-induced sickness
      behavior and clock gene dysregulation.
AB  - Autoimmune and infectious diseases are associated with behavioral changes
      referred to as sickness behavior syndrome (SBS). In autoimmunity, the generation
      of anti-self T lymphocytes and autoantibodies critically involves binding of CD40
      ligand on T-cells to its receptor CD40 on B-cells, dendritic cells and
      macrophages. Activation of CD40 leads to production of proinflammatory cytokines
      and, as shown here, induces SBS. Here we report that these behavioral changes
      depend on the expression of tumor necrosis factor alpha receptor 1 (TNFR1), but
      not on interleukin-1 receptor 1 or interleukin-6. Moreover, the intensity of SBS
      correlates with suppression of E-box controlled clock genes, including Dbp, and
      upregulation of Bmal1. However, the absence of TNFR1 does not interfere with the
      development of SBS and dysregulation of clock genes in mice treated with
      lipopolysaccharide. Thus, our results suggest that TNFR1 mediates SBS and
      dysregulation of clock genes in autoimmune diseases.

PMID- 21074605
TI  - Subventricular zone microglia transcriptional networks.
AB  - Microglia play an important role in inflammatory diseases of the central nervous
      system. There is evidence of microglial diversity with distinct phenotypes
      exhibiting either neuroprotection and repair or neurotoxicity. However the
      precise molecular mechanisms underlying this diversity are still unknown. Using a
      model of experimental autoimmune encephalomyelitis (EAE) we performed
      transcriptional profiling of isolated subventricular zone microglia from the
      acute and chronic disease phases of EAE. We found that microglia exhibit disease
      phase specific gene expression signatures, that correspond to unique gene
      ontology functions and genomic networks. Our data demonstrate for the first time,
      distinct transcriptional networks of microglia activation in vivo, that suggests
      a role as mediators of injury or repair.

PMID- 21074608
TI  - The stereochemical configuration of flavanols influences the level and metabolism
      of flavanols in humans and their biological activity in vivo.
AB  - Extensive epidemiological and clinical evidence associates diets high in flavanol
      containing foods with cardiovascular health benefits in humans. Catechin and
      epicatechin, the most common flavanols in foods, are present in the diet in
      different enantiomeric forms. This study investigated the influence of the
      stereochemical configuration of flavanols on their absorption, metabolism, and
      biological activity. Healthy adult males were asked to consume equal amounts of
      the stereochemically pure flavanols (-)-epicatechin, (-)-catechin, (+)-catechin,
      and (+)-epicatechin (1.5mg/kg bw) in a well-defined cocoa-based, dairy-containing
      drink matrix, and flavanol levels were subsequently determined in plasma and 24-h
      urine. The results obtained show that the stereochemical configuration of
      flavanols has a profound influence on their uptake and metabolism in humans. In
      addition, we assessed the vasodilatory activity of each flavanol stereoisomer in
      vivo and found (-)-epicatechin to be the single stereoisomer capable of mediating
      a significant arterial dilation response. Importantly, this effect was
      independent of the classic antioxidant properties of flavanols. Overall, these
      results indicate that the proposed beneficial health effects associated with the
      consumption of flavanol-containing foods will significantly depend on the
      stereochemical configuration of the flavanols ingested.

PMID- 21074607
TI  - NADPH oxidase 4 mediates TGF-beta-induced smooth muscle alpha-actin via p38MAPK
      and serum response factor.
AB  - In contrast to other cell types, vascular smooth muscle cells modify their
      phenotype in response to external signals. NADPH oxidase 4 (Nox4) is critical for
      maintenance of smooth muscle gene expression; however, the underlying mechanisms
      are incompletely characterized. Using smooth muscle alpha-actin (SMA) as a
      prototypical smooth muscle gene and transforming growth factor-beta (TGF-beta) as
      a differentiating agent, we examined Nox4-dependent signaling. TGF-beta increases
      Nox4 expression and activity in human aortic smooth muscle cells (HASMC).
      Transfection of HASMC with siRNA against Nox4 (siNox4) abolishes TGF-beta-induced
      SMA expression and stress fiber formation. siNox4 also significantly inhibits TGF
      beta-stimulated p38MAPK phosphorylation, as well as that of its substrate,
      mitogen-activated protein kinase-activated protein kinase-2. Moreover, the
      p38MAPK inhibitor SB-203580 nearly completely blocks the SMA increase induced by
      TGF-beta. Inhibition of either p38MAPK or NADPH oxidase-derived reactive oxygen
      species impairs the TGF-beta-induced phosphorylation of Ser103 on serum response
      factor (SRF) and reduces its transcriptional activity. Binding of SRF to
      myocardin-related transcription factor (MRTF) is also necessary, because
      downregulation of MRTF by siRNA abolishes TGF-beta-induced SMA expression. Taken
      together, these data suggest that Nox4 regulates SMA expression via activation of
      a p38MAPK/SRF/MRTF pathway in response to TGF-beta.

PMID- 21074609
TI  - Nonesterified cholesterol content of lysosomes modulates susceptibility to
      oxidant-induced permeabilization.
AB  - Reactive oxygen species (ROS) can induce lysosomal membrane permeabilization
      (LMP). Photoirradiation of murine hepatoma 1c1c7 cultures preloaded with the
      photosensitizer NPe6 generates singlet oxygen within acidic organelles and causes
      LMP and the activation of procaspases. Treatment with the cationic amphiphilic
      drugs (CADs) U18666A, imipramine, and clozapine stimulated the accumulation of
      filipin-stainable nonesterified cholesterol/sterols in late endosomes/lysosomes,
      but not in mitochondria. Concentration-response studies demonstrated an inverse
      relationship between lysosomal nonesterified cholesterol/sterol contents and
      susceptibility to NPe6 photoirradiation-induced intracellular membrane oxidation,
      LMP, and activation of procaspase-9 and -3. Similarly, the kinetics of
      restoration of NPe6 photoirradiation-induced LMP paralleled the losses of
      lysosomal cholesterol that occurred upon replating U18666A-treated cultures in
      CAD-free medium. Consistent with the oxidation of lysosomal cholesterol, filipin
      staining in U18666A-treated cultures progressively decreased with increasing
      photoirradiating light dose. U18666A also suppressed the induction of LMP and
      procaspase activation by exogenously added hydrogen peroxide. However, neither
      U18666A nor imipramine suppressed the induction of apoptosis by agents that did
      not directly induce LMP. These studies indicate that lysosomal nonesterified
      cholesterol/sterol content modulates susceptibility to ROS-induced LMP and
      possibly does so by being an alternative target for oxidants and lowering the
      probability of damage to other lysosomal membrane lipids and/or proteins.

PMID- 21074611
TI  - Biorelevant in vitro dissolution testing of products containing micronized or
      nanosized fenofibrate with a view to predicting plasma profiles.
AB  - The ability of in vitro biorelevant dissolution tests to predict the in vivo
      performance of nanosized fenofibrate (Lipidil 145 ONE(r)) and microsized
      fenofibrate (Lipidil - Ter(r)) was evaluated in this study. In vitro dissolution
      was carried out using USP apparatus 2 (paddle method) with updated biorelevant
      media to simulate the pre- and postprandial states. Membrane filters with
      different pore sizes were evaluated for their ability to hold back undissolved,
      nanosized drug particles. It was shown that filters with pore sizes of 0.1 MUm
      and 0.02 MUm were able to separate molecularly dissolved drug from colloidal and
      undissolved particles. In vitro results obtained with a suitable filter were used
      to generate simulated plasma profiles in combination with two different models
      using STELLA(r) software: (a) under the assumption of no permeability
      restrictions to absorption and (b) under the assumption of a permeability
      restriction. The simulated plasma profiles were compared to in vivo data for the
      nanosized and the microsized formulation in the fasted and fed states. The first
      model approach resulted in good correlation for the microsized fenofibrate
      formulation, but the plasma profile of the formulation containing nanosized
      fenofibrate was overpredicted in the fasted state. The second model successfully
      correlated with in vivo data for both formulations, regardless of prandial state.
      Comparison of simulations with the two models indicates that in the fasted state,
      absorption of fenofibrate from the nanosized formulation is at least partly
      permeability-limited, while for the microsized formulation the dissolution of
      fenofibrate appears to be rate-determining.

PMID- 21074612
TI  - Brain targeting with surface-modified poly(D,L-lactic-co-glycolic acid)
      nanoparticles delivered via carotid artery administration.
AB  - In this study, we investigated surface-modified nanoparticles (NP) formulated
      using a biodegradable polymer, poly(D,L-lactide-co-glycolide) (PLGA), for
      targeting central nervous system (CNS) diseases. Polysorbate 80 (P80), poloxamer
      188 (P188), and chitosan (CS) were used to modify the surfaces of PLGA NP to
      improve the brain delivery of NP. Surface-modified PLGA NP were formulated using
      an emulsion solvent diffusion method. 6-Coumarin was used as a fluorescent label
      for NP. The different formulations of 6-coumarin-loaded PLGA NP were injected
      into rats via carotid arteries. NP remaining in the brain were evaluated
      quantitatively, and brain slices were observed using confocal laser scanning
      microscopy (CLSM). Carotid artery administration was more effective for
      delivering NP into the brain compared to intravenous administration. After
      administration, NP concentrations in the brain were increased by NP surface
      modification, especially CS- and P80-PLGA NP. CLSM observations indicated that
      P80-PLGA NP could cross the blood-brain barrier and thus serve as a drug delivery
      system for the CNS. These results indicate that surface-modified PLGA NP have a
      high potential for use in CNS delivery systems.

PMID- 21074613
TI  - Influence of PEGylation with linear and branched PEG chains on the adsorption of
      glucagon to hydrophobic surfaces.
AB  - PEGylation has proven useful for prolonging the plasma half lives of proteins,
      and since approval of the first PEGylated protein drug product by the FDA in
      1990, several PEGylated protein drug products have been marketed. However, the
      influence of PEGylation on the behavior of proteins at interfaces is only poorly
      understood. The aim of this work was to study the effect of PEGylation on the
      adsorption of glucagon from aqueous solution to a hydrophobic surface and to
      compare the effects of PEGylation with a linear and a branched PEG chain,
      respectively. The 3483 Da peptide glucagon was PEGylated with a 2.2 kDa linear
      and a branched PEG chain, respectively, and the adsorption behaviors of the three
      proteins were compared using isothermal titration calorimetry, fixed-angle
      optical reflectometry and total internal reflection fluorescence. PEGylation
      decreased the number of glucagon molecules adsorbing per unit surface area and
      increased the initial adsorption rate of glucagon. Furthermore, the results
      indicated that the orientation and/or structural changes of glucagon upon
      adsorption were affected by the PEGylation. Finally, from the isothermal
      titration calorimetry and the reflectometry data, it was observed that the
      architecture of the PEG chains had an influence on the observed heat flow upon
      adsorption as well as on the initial rate of adsorption, respectively.

PMID- 21074610
TI  - Ventromedian forebrain dysgenesis follows early prenatal ethanol exposure in
      mice.
AB  - Ethanol exposure on gestational day (GD) 7 in the mouse has previously been shown
      to result in ventromedian forebrain deficits along with facial anomalies
      characteristic of fetal alcohol syndrome (FAS). To further explore ethanol's
      teratogenic effect on the ventromedian forebrain in this mouse model, scanning
      electron microscopic and histological analyses were conducted. For this, time
      mated C57Bl/6J mice were injected with 2.9g/kg ethanol or saline twice, at a 4h
      interval, on their 7th day of pregnancy. On GD 12.5, 13 and 17, control and
      ethanol-exposed specimens were collected and processed for light and scanning
      electron microscopic analyses. Gross morphological changes present in the
      forebrains of ethanol-exposed embryos included cerebral hemispheres that were too
      close in proximity or rostrally united, enlarged foramina of Monro, enlarged or
      united lateral ventricles, and varying degrees of hippocampal and ventromedian
      forebrain deficiency. In GD 12.5 control and ethanol-exposed embryos, in situ
      hybridization employing probes for Nkx2.1 or Fzd8 to distinguish the preoptic
      area and medial ganglionic eminences (MGEs) from the lateral ganglionic
      eminences, respectively, confirmed the selective loss of ventromedian tissues.
      Immunohistochemical labeling of oligodendrocyte progenitors with Olig2, a
      transcription factor necessary for their specification, and of GABA, an
      inhibitory neurotransmitter, showed ethanol-induced reductions in both. To
      investigate later consequences of ventromedian forebrain loss, MGE-derived
      somatostatin-expressing interneurons in the subpallial region of GD 17 fetal mice
      were examined, with results showing that the somatostatin-expressing interneurons
      that were present were dysmorphic in the ethanol-exposed fetuses. The potential
      functional consequences of this insult are discussed.

PMID- 21074614
TI  - Possible role of macrophages induced by an irridoid glycoside (RLJ-NE-299A) in
      host defense mechanism.
AB  - In order to explore the possible role of macrophages and other necessary immune
      competent (T and B) cells in the modulation of immune responses, an attempt was
      made to study the immunomodulatory effect of an irridoid glycoside (RLJ-NE-299A)
      isolated from the roots of Picrorhiza kurroa. Both in vitro and in vivo studies
      were used to evaluate the effect of RLJ-NE-299A on humoral, cellular, and
      phagocytic activity of macrophages. The data obtained in the present study showed
      that RLJ-NE-299A significantly increased sheep red blood cell (SRBC) and induced
      antibody (IgM and IgG) titer and delayed type hypersensitivity (DTH) reaction in
      mice. Besides augmenting the humoral and cell-mediated immune response, it
      induced macrophage phagocytosis and stimulated cytokine-induced macrophage
      activation and nitric oxide (NO) production, which resulted in a high degree of
      protection against Candida albicans and Salmonella typhimurium infections. Flow
      cytometric analysis indicated the enhanced expression of co-stimulatory surface
      molecules CD80 and CD86. The ability of RLJ-NE-299A to upregulate these cell
      surface antigens involved in antigen presentation may provide an explanation for
      the increased T-cell mediated immunity involving macrophages. Taken together this
      in vitro and in vivo preclinical data suggests that RLJ-NE-299A acts as an
      effective immunomodulator specifically to improve macrophage function during
      infections. The effects of this agent on these cells at concentrations relevant
      to in vivo therapy support its immunopharmacologic application to modify cellular
      immunity.

PMID- 21074615
TI  - The pathobiology of blast injuries and blast-induced neurotrauma as identified
      using a new experimental model of injury in mice.
AB  - Current experimental models of blast injuries used to study blast-induced
      neurotrauma (BINT) vary widely, which makes the comparison of the experimental
      results extremely challenging. Most of the blast injury models replicate the
      ideal Friedlander type of blast wave, without the capability to generate blast
      signatures with multiple shock fronts and refraction waves as seen in real-life
      conditions; this significantly reduces their clinical and military relevance.
      Here, we describe the pathophysiological consequences of graded blast injuries
      and BINT generated by a newly developed, highly controlled, and reproducible
      model using a modular, multi-chamber shock tube capable of tailoring pressure
      wave signatures and reproducing complex shock wave signatures seen in theater.
      While functional deficits due to blast exposure represent the principal health
      problem for today's warfighters, the majority of available blast models induces
      tissue destruction rather than mimic functional deficits. Thus, the main goal of
      our model is to reliably reproduce long-term neurological impairments caused by
      blast. Physiological parameters, functional (motor, cognitive, and behavioral)
      outcomes, and underlying molecular mechanisms involved in inflammation measured
      in the brain over the 30 day post-blast period showed this model is capable of
      reproducing major neurological changes of clinical BINT.

PMID- 21074616
TI  - Multipotent PDGFRbeta-expressing cells in the circulation of stroke patients.
AB  - Tissue pericytes respond to injury, and support vascular and tissue regeneration.
      The presence of pericytes in the circulation may provide an attractive framework
      for tissue regeneration. Here, we detected multipotent pericyte-like cells in the
      circulating blood and determined its profiles during cerebral ischemia. Pericyte
      like cells were isolated from the peripheral blood of acute stroke patients or
      asymptomatic individuals with vascular risk factors by fluorescence or magnetic
      activated cell sorting with anti-PDGF receptor-beta (PDGFRbeta) antibody. The
      morphologic and molecular features of circulating PDGFRbeta(+) cells were
      compared with tissue pericytes, and the associations with respect to quantity in
      the blood, culture outcome, and patient characteristics were analyzed. We found
      an increase in circulating PDGFRbeta(+) cells in acute stroke patients compared
      to controls and a correlation with neurologic impairment. The isolated
      PDGFRbeta(+) cells expressed mesenchymal stem cell markers, proliferated, and
      were multipotent under permissive culture conditions. The multipotent nature of
      these cells was comparable to fat-derived PDGFRbeta(+) cells. These cells could
      be obtained by pharmacologic stimulation using bone marrow mobilizer. Circulating
      PDGFRbeta(+) cells will be useful for future research involving endogenous
      recovery or autologous cell-based therapy.

PMID- 21074617
TI  - Purification process development of a recombinant monoclonal antibody expressed
      in glycoengineered Pichia pastoris.
AB  - A robust and scalable purification process was developed to quickly generate
      antibody of high purity and sufficient quantity from glycoengineered Pichia
      pastoris fermentation. Protein A affinity chromatography was used to capture the
      antibody from fermentation supernatant. A pH gradient elution was applied to the
      Protein A column to prevent antibody precipitation at low pH. Antibody from
      Protein A chromatography contained some product related impurities, which were
      the misassembling of cleaved heavy chain, heavy chain and light chain. It also
      had some process related impurities, including Protein A residues, endotoxin,
      host cell DNA and proteins. Cation exchange chromatography with optimal NaCl
      gradient at pH 4.5-6.0 efficiently removed these product and process related
      impurities. The antibody from glycoengineered P. pastoris was comparable to its
      commercial counterpart in heterotetramer folding, physical stability and binding
      affinity.

PMID- 21074618
TI  - Expression and purification of soluble murine CD40L monomers and polymers in
      yeast Pichia pastoris.
AB  - The anti-murine CD40L monoclonal antibody MR1 has been widely used in immunology
      research to block the CD40-CD40L interaction for induction of transplantation
      tolerance and to abrogate autoimmune diseases. The availability of recombinant
      CD40L with high binding capacity for MR1 would provide a valuable immunologic
      research tool. In this study, we constructed the single chain murine soluble
      CD40L monomer, dimer, trimer and successfully expressed them in yeast Pichia
      pastoris under the control of the alcohol oxidase promoter. The secreted single
      chain murine soluble CD40L monomers, dimers, and trimers were initially enriched
      through histidine tag capture by Ni-Sepharose 6 fast flow resin and further
      purified on a cation exchange resin. Purity reached more than 95% for the monomer
      and dimer forms and more than 90% for the trimer. Protein yield following
      purification was 16 mg/L for the monomer and dimer, and 8 mg/L for the trimer.
      ELISA analysis demonstrated that the CD40L dimers and trimers correctly folded in
      conformations exposing the MR1 antigenic determinant.

PMID- 21074620
TI  - NMR and small-angle scattering-based structural analysis of protein complexes in
      solution.
AB  - Structural analysis of multi-domain protein complexes is a key challenge in
      current biology and a prerequisite for understanding the molecular basis of
      essential cellular processes. The use of solution techniques is important for
      characterizing the quaternary arrangements and dynamics of domains and subunits
      of these complexes. In this respect solution NMR is the only technique that
      allows atomic- or residue-resolution structure determination and investigation of
      dynamic properties of multi-domain proteins and their complexes. As experimental
      NMR data for large protein complexes are sparse, it is advantageous to combine
      these data with additional information from other solution techniques. Here, the
      utility and computational approaches of combining solution state NMR with small
      angle X-ray and Neutron scattering (SAXS/SANS) experiments for structural
      analysis of large protein complexes is reviewed. Recent progress in experimental
      and computational approaches of combining NMR and SAS are discussed and
      illustrated with recent examples from the literature. The complementary aspects
      of combining NMR and SAS data for studying multi-domain proteins, i.e. where
      weakly interacting domains are connected by flexible linkers, are illustrated
      with the structural analysis of the tandem RNA recognition motif (RRM) domains
      (RRM1-RRM2) of the human splicing factor U2AF65 bound to a nine-uridine (U9) RNA
      oligonucleotide.

PMID- 21074619
TI  - Effects of phosphorylation on the self-assembly of native full-length porcine
      amelogenin and its regulation of calcium phosphate formation in vitro.
AB  - The self-assembly of the predominant extracellular enamel matrix protein
      amelogenin plays an essential role in regulating the growth and organization of
      enamel mineral during early stages of dental enamel formation. The present study
      describes the effect of the phosphorylation of a single site on the full-length
      native porcine amelogenin P173 on self-assembly and on the regulation of
      spontaneous calcium phosphate formation in vitro. Studies were also conducted
      using recombinant non-phosphorylated (rP172) porcine amelogenin, along with the
      most abundant amelogenin cleavage product (P148) and its recombinant form
      (rP147). Amelogenin self-assembly was assessed using dynamic light scattering
      (DLS) and transmission electron microscopy (TEM). Using these approaches, we have
      shown that self-assembly of each amelogenin is very sensitive to pH and appears
      to be affected by both hydrophilic and hydrophobic interactions. Furthermore, our
      results suggest that the phosphorylation of the full-length porcine amelogenin
      P173 has a small but potentially important effect on its higher-order self
      assembly into chain-like structures under physiological conditions of pH,
      temperature, and ionic strength. Although phosphorylation has a subtle effect on
      the higher-order assembly of full-length amelogenin, native phosphorylated P173
      was found to stabilize amorphous calcium phosphate for extended periods of time,
      in sharp contrast to previous findings using non-phosphorylated rP172. The
      biological relevance of these findings is discussed.

PMID- 21074621
TI  - Role of DNA-DNA interactions on the structure and thermodynamics of
      bacteriophages Lambda and P4.
AB  - Electrostatic interactions play an important role in both packaging of DNA inside
      bacteriophages and its release into bacterial cells. While at physiological
      conditions DNA strands repel each other, the presence of polyvalent cations such
      as spermine and spermidine in solutions leads to the formation of DNA
      condensates. In this study, we discuss packaging of DNA into bacteriophages P4
      and Lambda under repulsive and attractive conditions using a coarse-grained model
      of DNA and capsids. Packaging under repulsive conditions leads to the appearance
      of the coaxial spooling conformations; DNA occupies all available space inside
      the capsid. Under the attractive potential both packed systems reveal toroidal
      conformations, leaving the central part of the capsids empty. We also present a
      detailed thermodynamic analysis of packaging and show that the forces required to
      pack the genomes in the presence of polyamines are significantly lower than those
      observed under repulsive conditions. The analysis reveals that in both the
      repulsive and attractive regimes the entropic penalty of DNA confinement has a
      significant non-negligible contribution into the total energy of packaging.
      Additionally we report the results of simulations of DNA condensation inside
      partially packed Lambda. We found that at low densities DNA behaves as free
      unconfined polymer and condenses into the toroidal structures; at higher
      densities rearrangement of the genome into toroids becomes hindered, and
      condensation results in the formation of non-equilibrium structures. In all cases
      packaging in a specific conformation occurs as a result of interplay between
      bending stresses experienced by the confined polymer and interactions between the
      strands.

PMID- 21074623
TI  - Hinge-loop mutation can be used to control 3D domain swapping and amyloidogenesis
      of human cystatin C.
AB  - Cystatins are natural inhibitors of cysteine proteases, enzymes that are widely
      distributed in animals, plants, and microorganisms. Human cystatin C (hCC) has
      been also recognized as an aggregating protein directly involved in the formation
      of pathological amyloid fibrils, and these amyloidogenic properties greatly
      increase in a naturally occurring L68Q hCC variant. For a long time only dimeric
      structure of wild-type hCC has been known. The dimer is created through 3D domain
      swapping process, in which two parts of the cystatin structure become separated
      from each other and next exchanged between two molecules. Important role in the
      domain swapping plays the L1 loop, which connects the exchanging segments and,
      upon dimerization, transforms from a beta-turn into a part of a long beta-strand.
      In the very recently published first monomeric structure of human cystatin C (hCC
      stab1), dimerization was abrogated due to clasping of the beta-strands from the
      swapping domains by an engineered disulfide bridge. We have designed and
      constructed another mutated cystatin C with the smallest possible structural
      intervention, that is a single-point mutation replacing hydrophobic V57 from the
      L1 loop by polar asparagine, known as a stabilizer of a beta-turn motif. V57N hCC
      mutant occurred to be stable in its monomeric form and crystallized as a monomer,
      revealing typical cystatin fold with a five-stranded antiparallel beta-sheet
      wrapped around an alpha-helix. Here we report a 2.04 A resolution crystal
      structure of V57N hCC and discuss the architecture of the protein in comparison
      to chicken cystatin, hCC-stab1 and dimeric hCC.

PMID- 21074624
TI  - Algorithm for selection of optimized EPR distance restraints for de novo protein
      structure determination.
AB  - A hybrid protein structure determination approach combining sparse Electron
      Paramagnetic Resonance (EPR) distance restraints and Rosetta de novo protein
      folding has been previously demonstrated to yield high quality models (Alexander
      et al. (2008)). However, widespread application of this methodology to proteins
      of unknown structures is hindered by the lack of a general strategy to place spin
      label pairs in the primary sequence. In this work, we report the development of
      an algorithm that optimally selects spin labeling positions for the purpose of
      distance measurements by EPR. For the alpha-helical subdomain of T4 lysozyme
      (T4L), simulated restraints that maximize sequence separation between the two
      spin labels while simultaneously ensuring pairwise connectivity of secondary
      structure elements yielded vastly improved models by Rosetta folding. 54% of all
      these models have the correct fold compared to only 21% and 8% correctly folded
      models when randomly placed restraints or no restraints are used, respectively.
      Moreover, the improvements in model quality require a limited number of optimized
      restraints, which is determined by the pairwise connectivities of T4L alpha
      helices. The predicted improvement in Rosetta model quality was verified by
      experimental determination of distances between spin labels pairs selected by the
      algorithm. Overall, our results reinforce the rationale for the combined use of
      sparse EPR distance restraints and de novo folding. By alleviating the
      experimental bottleneck associated with restraint selection, this algorithm sets
      the stage for extending computational structure determination to larger,
      traditionally elusive protein topologies of critical structural and biochemical
      importance.

PMID- 21074625
TI  - Geographical variation in and evolutionary history of the Sunda clouded leopard
      (Neofelis diardi) (Mammalia: Carnivora: Felidae) with the description of a new
      subspecies from Borneo.
AB  - Recent morphological and molecular studies led to the recognition of two extant
      species of clouded leopards; Neofelis nebulosa from mainland southeast Asia and
      Neofelis diardi from the Sunda Islands of Borneo and Sumatra, including the Batu
      Islands. In addition to these new species-level distinctions, preliminary
      molecular data suggested a genetic substructure that separates Bornean and
      Sumatran clouded leopards, indicating the possibility of two subspecies of N.
      diardi. This suggestion was based on an analysis of only three Sumatran and seven
      Bornean individuals. Accordingly, in this study we re-evaluated this proposed
      subspecies differentiation using additional molecular (mainly historical) samples
      of eight Bornean and 13 Sumatran clouded leopards; a craniometric analysis of 28
      specimens; and examination of pelage morphology of 20 museum specimens and of
      photographs of 12 wild camera-trapped animals. Molecular (mtDNA and
      microsatellite loci), craniomandibular and dental analyses strongly support the
      differentiation of Bornean and Sumatran clouded leopards, but pelage
      characteristics fail to separate them completely, most probably owing to small
      sample sizes, but it may also reflect habitat similarities between the two
      islands and their recent divergence. However, some provisional discriminating
      pelage characters are presented that need further testing. According to our
      estimates both populations diverged from each other during the Middle to Late
      Pleistocene (between 400 and 120 kyr). We present a discussion on the
      evolutionary history of Neofelis diardi sspp. on the Sunda Shelf, a revised
      taxonomy for the Sunda clouded leopard, N. diardi, and formally describe the
      Bornean subspecies, Neofelis diardi borneensis, including the designation of a
      holotype (BM.3.4.9.2 from Baram, Sarawak) in accordance with the rules of the
      International Code of Zoological Nomenclature.

PMID- 21074622
TI  - Structural NMR of protein oligomers using hybrid methods.
AB  - Solving structures of native oligomeric protein complexes using traditional high
      resolution NMR techniques remains challenging. However, increased utilization of
      computational platforms, and integration of information from less traditional NMR
      techniques with data from other complementary biophysical methods, promises to
      extend the boundary of NMR-applicable targets. This article reviews several of
      the techniques capable of providing less traditional and complementary structural
      information. In particular, the use of orientational constraints coming from
      residual dipolar couplings and residual chemical shift anisotropy offsets are
      shown to simplify the construction of models for oligomeric complexes, especially
      in cases of weak homo-dimers. Combining this orientational information with
      interaction site information supplied by computation, chemical shift
      perturbation, paramagnetic surface perturbation, cross-saturation and mass
      spectrometry allows high resolution models of the complexes to be constructed
      with relative ease. Non-NMR techniques, such as mass spectrometry, EPR and small
      angle X-ray scattering, are also expected to play increasingly important roles by
      offering alternative methods of probing the overall shape of the complex.
      Computational platforms capable of integrating information from multiple sources
      in the modeling process are also discussed in the article. And finally a new,
      detailed example on the determination of a chemokine tetramer structure will be
      used to illustrate how a non-traditional approach to oligomeric structure
      determination works in practice.

PMID- 21074626
TI  - The phylogeny of advanced snakes (Colubroidea), with discovery of a new subfamily
      and comparison of support methods for likelihood trees.
AB  - The superfamily Colubroidea (> 2500 species) includes the majority of snake
      species and is one of the most conspicuous and well-known radiations of
      terrestrial vertebrates. However, many aspects of the phylogeny of the group
      remain contentious, and dozens of genera have yet to be included in molecular
      phylogenetic analyses. We present a new, large-scale, likelihood-based phylogeny
      for the colubroids, including 761 species sampled for up to five genes:
      cytochrome b (93% of 761 species sampled), ND4 (69%), ND2 (28%), c-mos (54%), and
      RAG-1 (13%), totaling up to 5814bp per species. We also compare likelihood
      bootstrapping and a recently proposed ultra-fast measure of branch support
      (Shimodaira-Hasegawa-like [SHL] approximate likelihood ratio), and find that the
      SHL test shows strong support for several clades that were weakly-supported by
      bootstrapping in this or previous analyses (e.g., Dipsadinae, Lamprophiidae). We
      find that SHL values are positively related to branch lengths, but show stronger
      support for shorter branches than bootstrapping. Despite extensive missing data
      for many taxa (mean=67% per species), neither bootstrap nor SHL support values
      for terminal species are related to their incompleteness, and that most highly
      incomplete taxa are placed in the expected families from previous taxonomy,
      typically with very strong support. The phylogeny indicates that the Neotropical
      colubrine genus Scaphiodontophis represents an unexpectedly ancient lineage
      within Colubridae. We present a revised higher-level classification of
      Colubroidea, which includes a new subfamily for Scaphiodontophis
      (Scaphiodontophiinae). Our study provides the most comprehensive phylogeny of
      Colubroidea to date, and suggests that SHL values may provide a useful complement
      to bootstrapping for estimating support on likelihood-based trees.

PMID- 21074627
TI  - Unresolved molecular phylogenies of gibbons and siamangs (Family: Hylobatidae)
      based on mitochondrial, Y-linked, and X-linked loci indicate a rapid Miocene
      radiation or sudden vicariance event.
AB  - According to recent taxonomic reclassification, the primate family Hylobatidae
      contains four genera (Hoolock, Nomascus, Symphalangus, and Hylobates) and between
      14 and 18 species, making it by far the most species-rich group of extant
      hominoids. Known as the "small apes", these small arboreal primates are
      distributed throughout Southeast, South and East Asia. Considerable uncertainty
      surrounds the phylogeny of extant hylobatids, particularly the relationships
      among the genera and the species within the Hylobates genus. In this paper we use
      parsimony, likelihood, and Bayesian methods to analyze a dataset containing
      nearly 14 kilobase pairs, which includes newly collected sequences from X-linked,
      Y-linked, and mitochondrial loci together with data from previous mitochondrial
      studies. Parsimony, likelihood, and Bayesian analyses largely failed to find a
      significant difference among phylogenies with any of the four genera as the most
      basal taxon. All analyses, however, support a tree with Hylobates and
      Symphalangus as most closely related genera. One strongly supported phylogenetic
      result within the Hylobates genus is that Hylobates pileatus is the most basal
      taxon. Multiple analyses failed to find significant support for any singular
      genus-level phylogeny. While it is natural to suspect that there might not be
      sufficient data for phylogenetic resolution (whenever that situation occurs), an
      alternative hypothesis relating to the nature of gibbon speciation exists. This
      lack of resolution may be the result of a rapid radiation or a sudden vicariance
      event of the hylobatid genera, and it is likely that a similarly rapid radiation
      occurred within the Hylobates genus. Additional molecular and paleontological
      evidence are necessary to better test among these, and other, hypotheses of
      hylobatid evolution.

PMID- 21074628
TI  - The association between knee joint biomechanics and neuromuscular control and
      moderate knee osteoarthritis radiographic and pain severity.
AB  - OBJECTIVE: The objective of this study was to determine the association between
      biomechanical and neuromuscular factors of clinically diagnosed mild to moderate
      knee osteoarthritis (OA) with radiographic severity and pain severity separately.
      METHOD: Three-dimensional gait analysis and electromyography were performed on a
      group of 40 participants with clinically diagnosed mild to moderate medial knee
      OA. Associations between radiographic severity, defined using a visual analog
      radiographic score, and pain severity, defined with the pain subscale of the
      WOMAC osteoarthritis index, with knee joint kinematics and kinetics,
      electromyography patterns of periarticular knee muscles, BMI and gait speed were
      determined with correlation analyses. Multiple linear regression analyses of
      radiographic and pain severity were also explored. RESULTS: Statistically
      significant correlations between radiographic severity and the overall magnitude
      of the knee adduction moment during stance (r2=21.4%, P=0.003) and the magnitude
      of the knee flexion angle during the gait cycle (r2=11.4%, P=0.03) were found.
      Significant correlations between pain and gait speed (r2=28.2%, P<0.0001), the
      activation patterns of the lateral gastrocnemius (r2=16.6%, P=0.009) and the
      medial hamstring (r2=10.3%, P=0.04) during gait were found. The combination of
      the magnitude of the knee adduction moment during stance and BMI explained a
      significant portion of the variability in radiographic severity (R(2)=27.1%,
      P<0.0001). No multivariate model explained pain severity better than gait speed
      alone. CONCLUSIONS: This study suggests that some knee joint biomechanical
      variables are associated with structural knee OA severity measured from
      radiographs in clinically diagnosed mild to moderate levels of disease, but that
      pain severity is only reflected in gait speed and neuromuscular activation
      patterns. A combination of the knee adduction moment and BMI better explained
      structural knee OA severity than any individual factor alone.

PMID- 21074629
TI  - Effects of dizocilpine (MK801) on olfactory span in rats.
AB  - NMDA receptor antagonists interfere with learning and memory in some tasks, but
      not others. Some recent accounts have suggested that tasks placing demands on
      working memory are those most likely to be affected, and the present study tested
      this hypothesis. The purpose of the study was to adapt a recently developed
      procedure designed to test working memory capacity, the olfactory memory span
      task, for use in behavioral pharmacology and to then determine the effects of the
      NMDA receptor antagonist, dizocilpine (MK801) on performance in this task. Rats
      were trained in a non-match-to-sample procedure under conditions in which they
      had to remember an increasing number of olfactory stimuli as the session
      progressed. Simple olfactory discrimination trials were interspersed to provide a
      performance control. Effects of dizocilpine (.03, .10, .17, .3mg/kg) were
      determined after stable performances were obtained. Rats were able to sustain
      stable performances on both the span and simple discrimination tasks with average
      spans of about 10 items. Accuracy declined as the number of stimuli to remember
      increased, and dizocilpine impaired accuracy in a dose-dependent and memory-load
      dependent fashion. The finding that the effects of dizocilpine interacted with
      the number of stimuli to remember is generally consistent with hypotheses linking
      NMDA receptors and working memory processes.

PMID- 21074630
TI  - A Phase I trial: dose escalation of melphalan in the "BEAM" regimen using
      amifostine cytoprotection.
AB  - With the eventual goal of reducing relapse and thus improving overall survival in
      selected lymphoma patients, a Phase I study was performed using the
      cytoprotectant amifostine to permit safe dose-augmentation of melphalan in the
      carmustine (BCNU), etoposide, cytarabine (arabinosylcytosine), and melphalan
      (BEAM) regimen before autologous hematopoietic stem cell transplantation. Between
      30 July 2003 and 25 November 2008, a total of 32 lymphoma patients were entered,
      of which 28 were evaluable. We found the melphalan dose in BEAM could be safely
      escalated to at least 260 mg/m2, a substantial increase from the usual dose of
      140 mg/m2 in BEAM while the trial was terminated early due to poor accrual, no
      maximal tolerated dose or dose-limiting toxicity was found. A Phase II trial is
      planned.

PMID- 21074631
TI  - Eosinophils, bronchitis and asthma: pathogenesis of cough and airflow
      obstruction.
AB  - Eosinophilic airway inflammation is commonly observed in chronic cough in
      patients with asthma and non-asthmatic eosinophilic bronchitis. Indeed asthma and
      non-asthmatic eosinophilic bronchitis are amongst the commonest causes of chronic
      cough accounting for about 25 and 10% of cases respectively. In most cases the
      trigger that causes the cough is uncertain; however removal of potential triggers
      is important to consider in particular with respect to occupational exposure to
      known sensitizers. In both conditions the cough improves subjectively and
      objectively following treatment with corticosteroids. This improvement is
      associated with the presence of an airway eosinophilia, but whether eosinophilic
      inflammation is the cause of cough or an epiphenomenon is uncertain. The success
      of anti-IL5 to reduce eosinophilic inflammation and asthma exacerbations
      contrasts with the lack of efficacy to modify cough in asthma and therefore
      challenges a causal association. Both asthma and non-asthmatic eosinophilic
      bronchitis can lead onto airway remodeling and result in persistent airflow
      obstruction. However, response to corticosteroid therapy in both conditions is
      generally very good and the limited long term data available suggests that both
      usually have a benign course. Interestingly, improvement in airway remodeling in
      response to anti-IL5 observed using CT imaging and analysis of sub-epithelial
      matrix deposition does suggest that the eosinophil may play a causal role in
      airway remodeling.

PMID- 21074632
TI  - TRPA1 receptors in cough.
AB  - In the early 1990's ion channels of the Transient Receptor Potential (TRP) class
      were implicated in the afferent sensory loop of the cough reflex and in the
      heightened cough sensitivity seen in disease. Agonists of the TRPV1 capsaicin
      receptor such as vanilloids and protons were demonstrated to be amongst the most
      potent chemical stimuli which cause cough. However, more recently, the TRPA1
      receptor (not activated by capsaicin) has become of interest in the cough field
      because it is known to be activated by ligands such as acrolein which is present
      in air pollution and the acrid smoke from organic material. TRPA1 is a Ca(2+)
      permeant non-selective cation channel with 14 ankyrin repeats in its amino
      terminus which belongs to the larger TRP family. TRPA1 has been characterised as
      a thermoreceptor which is activated by cold temperature, environmental irritants
      and reactive electrophilic molecules which can be generated by oxidant stress and
      inflammation. TRPA1 is primarily expressed in small diameter, nociceptive neurons
      where its activation probably contributes to the perception of noxious stimuli
      and the phenomena known as inflammatory hyperalgesia and neurogenic inflammation.
      The respiratory tract is innervated by primary sensory afferent nerves which are
      activated by mechanical and chemical stimuli. Activation of these vagal sensory
      afferents leads to central reflexes including dyspnoea, changes in breathing
      pattern and cough. Recently, it has been demonstrated that stimulating TRPA1
      channels activates vagal bronchopulmonary C-fibres in the guinea pig and rodent
      lung, and recent data have shown that TRPA1 ligands cause cough in both animal
      models and normal volunteers. In summary, due to their activation by a wide range
      of irritant and chemical substances, either by exogenous agents, endogenously
      produced mediators during inflammation or by oxidant stress, we suggest TRPA1
      channels should be considered as one of the most promising targets currently
      identified for the development of novel anti-tussive drugs.

PMID- 21074633
TI  - Metabolic rate and oxidative stress in insects exposed to low temperature thermal
      fluctuations.
AB  - Fluctuating temperatures are a predominant feature of the natural environment but
      their effects on ectotherm physiology are not well-understood. The warm periods
      of fluctuating thermal regimes (FTRs) provide opportunities for repair leading to
      increased survival, but there are also indications of negative effects of warm
      exposure. In this study, we examined respiration and oxidative stress in adult
      Alphitobius diaperinus exposed to FTRs and to constant low temperatures. We
      hypothesized that cold exposure will cause oxidative stress and that FTRs would
      reduce the amount of chill injuries, via activation of the antioxidant system. We
      measured VCO2, activities of super oxide dismutase (SOD), amounts of total (GSHt)
      and oxidized glutathione (GSSG) during cold and warm periods of FTRs. Increased
      severity of cold exposure caused a decrease in the glutathione pool. SOD levels
      increased during the recovery period in the more severe FTR. The antioxidant
      response was sufficient to counter the reactive oxygen species production, as the
      GSH:GSSG ratio increased. We conclude that cold stress causes oxidative damage in
      these beetles, and that a warm recovery period activates the antioxidant system
      allowing repair of cold-induced damage, leading to the increased survival
      previously noted in beetles exposed to fluctuating versus constant temperatures.

PMID- 21074634
TI  - The graphical representation of ADME-related molecule properties for medicinal
      chemists.
AB  - The importance of striving for and maintaining drug-like physicochemical
      properties during the hit and lead optimization process is now well documented,
      and many published studies have suggested optimal ranges and/or limits for key
      molecule descriptors such as size, lipophilicity, H-bonding characteristics,
      rotatable bond and aromatic ring counts, particularly with regard to the design
      of orally administered drugs. The aim of this article is to review various
      approaches that have been used to represent molecule properties graphically in
      the context of oral 'drug likeness', with the goal of improving the decision
      making of medicinal chemists during the drug discovery process.

PMID- 21074635
TI  - Re-formulating drugs and vaccines for intranasal delivery: maximum benefits for
      minimum risks?
AB  - The challenges being faced by the pharmaceutical industry in terms of patent
      expiries and a sparse pipeline of new products are well documented, as are the
      risks and costs associated with developing new molecular entities. Major
      pharmaceutical companies are increasingly looking to augment their traditional
      core expertise in the discovery of small molecules with the development of
      biologicals (e.g. peptide-based, protein-based, antibody-based and nucleic-acid
      based therapies), which are seen as a key element in achieving long-term growth.
      There is also considerable current interest in vaccines, both in the traditional
      area of mass immunization against infections and as a novel approach to disease
      treatment.

PMID- 21074636
TI  - Tissue-specific expression of Sarcoplasmic/Endoplasmic Reticulum Calcium ATPases
      (ATP2A/SERCA) 1, 2, 3 during Xenopus laevis development.
AB  - Calcium-ATPase pumps are critical in most cells, to sequester calcium into
      intracytoplasmic stores and regulate general calcium signalling. In addition,
      cell-specific needs for calcium signals have been described and employ a
      diversity of calcium ATPases in adult tissues and oocytes. A major family of such
      calcium pumps is ATP2A/SERCA family, for Sarcoplasmic/Endoplasmic Reticulum
      Calcium ATPases. Although largely studied in adults, the developmental expression
      of the atp2a/serca genes remains unknown. Here, we provide genome organisation in
      Xenopuslaevis and tropicalis and phylogeny of atp2a/serca genes in craniates. We
      detail embryonic expression for the three X. laevis atp2a/serca genes. We found
      that the three atp2a/serca genes are strongly conserved among vertebrates and
      display complementary and tissue-specific expression in embryos. These expression
      patterns present variations when compared to the data reported in adults.
      Atp2a1/serca1 is expressed as soon as the end of gastrulation in a subset of the
      myod-positive cells, and later labels prospective slow muscle cells in the
      superficial part of the somite. In contrast atp2a2/serca2 is found in a larger
      subset of cells, but is not ubiquitous as reported in adults. Notably,
      atp2a2/serca2 is prominently expressed in the neural-related tissues, i.e. the
      neural plate, cement gland, but is excluded from premigratory neural crest.
      Finally, atp2a3/serca3 expression is restricted to the ectoderm throughout
      development.

PMID- 21074637
TI  - Are associations of immune gene expression, body condition and parasite burden
      detectable in nature? A case study in an endemic rodent from the Brazilian
      Atlantic Forest.
AB  - Host-parasite co-evolutionary processes are the most important drivers shaping
      the host's immune system. During successful host immune responses to helminthic
      infections, usually a balanced cascade of different immune genes like MHC, T
      helper cell 1 and 2 (Th1 and Th2) cytokines is expressed. This information comes
      largely from human or laboratory studies. The situation under which the immune
      system has evolved, however, is more complicated and natural variation need to be
      included to provide a more complete picture of co-evolutionary processes. We
      employed quantitative real-time PCR (qPCR) to explore associations of immune gene
      expression, body mass index (BMI) and helminth burden in a wild population of a
      non-model rodent (Delomys sublineatus). Our study shows that a typical Th2
      response with a combination of inflammatory and anti-inflammatory components is
      detectable also under natural conditions. Complex associations of the expression
      levels of TGF-beta, IL-10, IL-4 and IL-2 with different parasites and with the
      number of different helminth infections, respectively, were detected. A positive
      association of the body mass index with the expression of IL-2 and IL-4 may
      indicate a link between host condition and the inflammatory part of an immune
      reaction. Our study shows for the first time that despite several potentially
      confounding parameters naturally present in a wildlife study, typical patterns of
      immune gene expression are detectable and influence helminth burden. Thus, in
      addition to structural variance of immune-relevant genes their expression might
      reflect host-parasite coevolutionary processes.

PMID- 21074638
TI  - Dysregulation of human Toll-like receptor function in aging.
AB  - Studies addressing immunosenescence in the immune system have expanded to focus
      on the innate as well as the adaptive responses. In particular, aging results in
      alterations in the function of Toll-like receptors (TLRs), the first described
      pattern recognition receptor family of the innate immune system. Recent studies
      have begun to elucidate the consequences of aging on TLR function in human
      cohorts and add to existing findings performed in animal models. In general,
      these studies show that human TLR function is impaired in the context of aging,
      and in addition there is evidence for inappropriate persistence of TLR activation
      in specific systems. These findings are consistent with an overarching theme of
      age-associated dysregulation of TLR signaling that likely contributes to the
      increased morbidity and mortality from infectious diseases found in geriatric
      patients.

PMID- 21074639
TI  - Excess of autoimmune and chronic inflammatory disorders in patients with lymphoma
      compared with all cancer patients: a cancer registry-based analysis in the south
      of the Netherlands.
AB  - OBJECTIVE: We investigated the association between autoimmune and chronic
      inflammatory disorders and several cancer types including lymphomas. METHODS: All
      cancer patients diagnosed between 1995 and 2007, aged 15 to 90 years, and
      registered in the Eindhoven Cancer Registry were included in this study. Co
      morbidity at diagnosis was recorded by qualified registry personnel who obtained
      the information from the clinical record. We determined the prevalence of
      rheumatoid arthritis (RA), chronic inflammatory bowel diseases, connective and
      vascular tissue diseases, ulcers of the stomach and duodenum, hepatitis, human
      immunodeficiency virus (HIV), and tuberculosis (TBC) among newly diagnosed
      patients with lymphoma and compared this with the prevalence among patients with
      all other cancers. RESULTS: The prevalence of most of these co-morbidities was
      higher in patients with lymphomas than those with other malignancies. RA was more
      often present in newly diagnosed patients with most lymphomas, ulcers of stomach
      and duodenum in patients with marginal zone lymphoma, hepatitis in case of
      diffuse large B-cell lymphoma, HIV with aggressive B-cell lymphoma, and TBC with
      mantle cell lymphoma. CONCLUSION: This study confirms the positive association
      between autoimmune and chronic inflammatory disorders and the various
      lymphoproliferative malignancies, suggesting either a shared etiology or
      pathogenesis or a direct causal relation. This is a fairly new method to study
      aetiological questions about cancers in a population-based cancer registry.

PMID- 21074640
TI  - Early osteogenic signal expression of rat bone marrow stromal cells is influenced
      by both hydroxyapatite nanoparticle content and initial cell seeding density in
      biodegradable nanocomposite scaffolds.
AB  - Incorporation of hydroxyapatite (HA) within a degradable polymeric scaffold may
      provide a favorable synthetic microenvironment that more closely mimics natural
      bone tissue physiology. Both incorporation of HA nanoparticles and alterations of
      the paracrine cell-cell signaling distance may affect the intercellular signaling
      mechanism and facilitate enhanced osteogenic signal expression among the
      implanted cell population. In this study we investigate the effect of the
      incorporation of HA nanoparticles into poly(propylene fumarate) (PPF) scaffolds
      on the surface properties of composite scaffolds and early osteogenic growth
      factor gene expression in relation to initial cell seeding density. The results
      of surface characterization indicated that HA addition improved the surface
      properties of PPF/HA composite scaffolds by increasing the roughness,
      hydrophilicity, protein adsorption, and initial cell attachment. Rat bone marrow
      stromal cells (BMSCs), which were CD34-, CD45-, CD29+, and CD90+, were cultured
      on three-dimensional (3-D) macroporous PPF/HA scaffolds at two different initial
      cell seeding densities (0.33 and 1.00 million cells per scaffold) for 8 days. The
      results demonstrated that endogenous osteogenic signal expression profiles,
      including bone morphogenetic protein-2, fibroblast growth factor-2, and
      transforming growth factor-beta1, as well as the transcriptional factor Runx2,
      were affected by both HA amount and initial cell seeding density. Up-regulated
      expression of osteogenic growth factor genes was related to subsequent
      osteoblastic differentiation of rat BMSCs on 3-D scaffolds, as characterized by
      alkaline phosphatase activity, osteocalcin mRNA expression, and calcium
      deposition. Thus, the PPF/HA composite scaffold construction parameters,
      including amount of HA incorporated and initial cell seeding density, may be
      utilized to induce the osteoblastic differentiation of transplanted rat BMSCs.

PMID- 21074642
TI  - Simple chemical tools to expand the range of proteomics applications.
AB  - Proteomics is an expanding technology with potential applications in many
      research fields. Even though many research groups do not have direct access to
      its main analytical technique, mass spectrometry, they can interact with
      proteomics core facilities to incorporate this technology into their projects.
      Protein identification is the analysis most frequently performed in core
      facilities and is, probably, the most robust procedure. Here we discuss a few
      chemical reactions that are easily implemented within the conventional protein
      identification workflow. Chemical modification of proteins with N
      hydroxysuccinimide esters, 4-sulfophenyl isothiocyanate, O-methylisourea or
      through beta-elimination/Michael addition can be easily performed in any
      laboratory. The reactions are quite specific with almost no side reactions. These
      chemical tools increase considerably the number of applications and have been
      applied to characterize protein-protein interactions, to determine the N-terminal
      residues of proteins, to identify proteins with non-sequenced genomes or to
      locate phosphorylated and O-glycosylated.

PMID- 21074641
TI  - Early biosignature of oxidative stress in the retinal pigment epithelium.
AB  - The retinal pigment epithelium (RPE) is essential for retinoid recycling and
      phagocytosis of photoreceptors. Understanding of proteome changes that mediate
      oxidative stress-induced degeneration of RPE cells may provide further insight
      into the molecular mechanisms of retinal diseases. In the current study,
      comparative proteomics has been applied to investigate global changes of RPE
      proteins under oxidative stress. Proteomic techniques, including 2D SDS-PAGE,
      differential gel electrophoresis (DIGE), and tandem time-of-flight (TOF-TOF) mass
      spectrometry, were used to identify early protein markers of oxidative stress in
      the RPE. Two biological models of RPE cells revealed several differentially
      expressed proteins that are involved in key cellular processes such as energy
      metabolism, protein folding, redox homeostasis, cell differentiation, and
      retinoid metabolism. Our results provide a new perspective on early signaling
      molecules of redox imbalance in the RPE and putative therapeutic target proteins
      of RPE diseases caused by oxidative stress.

PMID- 21074643
TI  - Guest editorial: Evidence-based practice: destination or journey?

PMID- 21074644
TI  - Making a difference in the health care of veterans: 9 things you should know.

PMID- 21074645
TI  - Professional nursing societies and evidence-based practice: strategies to cross
      the quality chasm.
AB  - The Institute of Medicine (IOM) published Crossing the Quality Chasm: A New
      Health Care System for the 21st Century nearly 10 years ago. Nursing societies
      are in a unique position to promote evidence-based practice (EBP). The purpose of
      this article is to describe EBP strategies that nursing societies can use to
      improve the quality of health care, thus decreasing the gap between research
      knowledge and practice. Nursing societies can take the lead in two key EBP
      activities: (1) development of evidence-based syntheses, systematic reviews, and
      guidelines for EBP; and (2) development, implementation, and testing strategies
      for these EBP resources to become available and used in clinical decision-making.
      The Oncology Nursing Society will be discussed as an exemplar of developing EBP
      programs and increasing knowledge of EBP and practice change resources for its
      members. The discussion stresses the importance of nursing society members and
      leaders in guiding their societies to contribute to the closing of the US health
      care quality chasm.

PMID- 21074647
TI  - Correlates among cognitive beliefs, EBP implementation, organizational culture,
      cohesion and job satisfaction in evidence-based practice mentors from a community
      hospital system.
AB  - Evidence from research and outcomes management projects strongly supports the use
      of evidence-based practice (EBP) in improving quality of health care and patient
      outcomes as well as reducing hospital costs. In addition, published anecdotal
      reports have indicated that clinicians who use an evidence-based approach to care
      and practice in cultures that support EBP feel more empowered and satisfied in
      their roles. However, research is lacking that has specifically examined the
      relationships among beliefs about and implementation of EBP by hospital staff,
      organizational culture for EBP, group cohesion and job satisfaction. Therefore,
      the purpose of this descriptive correlational study was to examine the
      relationships among these variables in 58 health professionals, prior to their
      participation in a 12-month EBP mentorship program as part of implementing the
      Advancing Research and Clinical practice through close Collaboration (ARCC) Model
      in a community hospital system. Findings indicated that participants' EBP beliefs
      were significantly correlated with perceived organizational culture for EBP, the
      extent to which they implemented EBP, group cohesion, and job satisfaction.
      Organizational culture for EBP was significantly and positively related to EBP
      beliefs and EBP implementation. Findings support the need for hospitals to
      establish cultures that support EBP and to implement strategies to strengthen
      individuals' cognitive beliefs about the value of EBP and their ability to
      implement it for the ultimate purpose of improving quality of care and enhancing
      job satisfaction.

PMID- 21074649
TI  - [What exactly is a medical device?].

PMID- 21074646
TI  - A thematic analysis of theoretical models for translational science in nursing:
      mapping the field.
AB  - The quantity and diversity of conceptual models in translational science may
      complicate rather than advance the use of theory. This paper offers a comparative
      thematic analysis of the models available to inform knowledge development,
      transfer, and utilization. Literature searches identified 47 models for knowledge
      translation. Four thematic areas emerged: (1) evidence-based practice and
      knowledge transformation processes, (2) strategic change to promote adoption of
      new knowledge, (3) knowledge exchange and synthesis for application and inquiry,
      and (4) designing and interpreting dissemination research. This analysis
      distinguishes the contributions made by leaders and researchers at each phase in
      the process of discovery, development, and service delivery. It also informs the
      selection of models to guide activities in knowledge translation. A flexible
      theoretical stance is essential to simultaneously develop new knowledge and
      accelerate the translation of that knowledge into practice behaviors and programs
      of care that support optimal patient outcomes.

PMID- 21074648
TI  - Interdisciplinary evidence-based practice: moving from silos to synergy.
AB  - Despite the assumption that health care providers work synergistically in
      practice, professions have tended to be more exclusive than inclusive when it
      comes to educating students in a collaborative approach to interdisciplinary
      evidence-based practice (EBP). This article explores the state of academic and
      clinical training regarding interdisciplinary EBP, describes efforts to foster
      interdisciplinary EBP, and suggests strategies to accelerate the translation of
      EBP across disciplines. Moving from silos to synergy in interdisciplinary EBP
      will require a paradigm shift. Changes can be leveraged professionally and
      politically using national initiatives currently in place on improving quality
      and health care reform.

PMID- 21074650
TI  - [Overview of five years of occupational dermatology: The role of atopy].
AB  - BACKGROUND: The management of occupational dermatitis is often complex and relies
      on skills in both dermatology and occupational medicine. A bidisciplinary
      occupational dermatology consultation was set up in 2002 at Brest CHU. The aim of
      this study is to provide an assessment of 5 years of activity and to discuss the
      role of atopy. PATIENTS AND METHODS: From October 2002 to October 2007, 245
      patients attended this consultation. 145 files concerning proven occupational
      dermatosis were studied (age, sex, occupation, dermatosis, allergens and history
      of atopy). One hundred and five patients completed a telephone questionnaire
      concerning their feelings about the consultation, the course of their dermatosis
      and the medicosocial outcome. RESULTS: The main forms of dermatosis were contact
      eczema (41%), irritant dermatitis (26%), exacerbation of atopic dermatitis (10%),
      associated eczema and irritant dermatitis (9%), and other (14%). DISCUSSION: The
      occupations of subjects (healthcare, building and civil engineering work, food
      and catering, agriculture, mechanics, hairdressing, cleaning, printing) and the
      allergens involved were similar to those described in the literature. The
      prognosis was poor (48% cure rate). Differential diagnosis between allergic
      eczema and irritant dermatitis was sometimes difficult and was based on clinical
      features and allergology tests. A history of atopy was found in 32% of patients
      and was particularly frequent among patients presenting allergic eczema
      associated with irritant dermatitis: this may be explained by the
      physiopathological mechanisms of atopic dermatitis (impairment of barrier
      function causing contact sensitization to potential allergens). CONCLUSION: Such
      a bidiscipinary occupational dermatology consultation has the advantage of
      optimizing management of these patients. Wider notification of occupational
      dermatosis would increase our knowledge of the causes of this condition and
      enable better prevention.

PMID- 21074651
TI  - [Results of skin tests to assess drug-induced allergy].
AB  - BACKGROUND: Skin tests are often used to explore adverse drug reactions. The
      sensitivity of skin tests appears to vary according to the drugs tested and the
      type of adverse reaction in question. There is no clear strategy to explore drug
      adverse reactions. The aim of this study was to determine the frequency of
      positive results for the different skin tests according to therapeutic class
      tested and type of adverse reaction. The secondary objective was to study
      response to the test drugs at different dilutions. PATIENTS AND METHODS: We
      retrospectively selected all patients presenting a suspected adverse drug
      reaction investigated in our clinic by patch test (PT), prick test (pt) and
      intradermal test (IDT). The suspected drugs and a pre-established list of
      substances from the same therapeutic family were systematically tested. Medical
      records from patients with Lyell syndrome, fixed drug eruption, photosensitivity
      and Drug Eruption with Eosinophilia and Systemic Symptoms (DRESS) syndrome were
      excluded. Adverse drug reactions were divided into two groups: the U group
      (urticaria or angioedema) and the E group (maculopapular-rash, erythroderma and
      generalized eczema). RESULTS: Four hundred and twenty-nine adverse drug reactions
      in 319 patients were assessed: 200 in the U group and 229 in the E group. In
      total, 61.8% presented at least one positive test for the suspected therapeutic
      class: 67.5% in the U group and 56.8% in the E group. In the U group, patch tests
      were positive in 14% of cases for betalactams, 17% for NSAIDs and 6% for radio
      contrast media (RCM); in the E group, PT were positive in 12% of cases for
      betalactams, 9% for NSAIDs and 2% for RCM. Prick-tests were positive in the U
      group in 73% of the betalactams explored, 40% for the NSAIDs and 40% for the RCM;
      in the E group, pt were positive in 51% for betalactams, 32 for NSAIDs and 35%
      for RCM. IDT were positive in the U group in 13% for betalactams, 10% for NSAIDs
      and 40% for RCM; in the E group, IDT were positive in 14% for betalactams, 7% for
      NSAIDs and 40% for RCM. In the U group, pt were positive in 50% of cases with a
      diluted aliquot and in 48% of cases for IDT; in the E group pt were positive in
      3% of cases with a diluted aliquot and in 63% of cases for IDT. The main
      limitations of this study are due to its retrospective nature and to the absence
      of evaluation of the specificity and relevance of the positive tests. CONCLUSION:
      In patients presenting adverse drug reactions such as urticaria, angioedema,
      maculopapular rash, erythroderma and generalized eczema, the frequency of
      positive tests is high in general and for each therapeutic class (betalactams,
      NSAIDs, RCM). Diluted aliquots for pt remained sensitive and could be useful in
      exploring urticaria or angioedema, in the same way as diluted aliquots for IDT in
      both types of reaction. Better standardization of test procedures (including
      diluted aliquots) and of result reading would improve evaluation of the
      specificity and relevance of skin tests in adverse drug reactions.

PMID- 21074652
TI  - [Oral lesions in psoriasis].
AB  - BACKGROUND: The literature contains little information about the incidence or
      prevalence of oral signs in psoriasis. The pustular forms are the most commonly
      incriminated, with geographic tongue being the most frequently cited oral sign.
      The aim of our study was to determine the various types of oral signs seen in a
      large population of psoriasis patients. PATIENTS AND METHODS: Four hundred
      psoriasis patients were recruited consecutively and a detailed oral examination
      performed by two clinicians. Similar examinations were performed over the same
      period in 1000 nonpsoriasis subjects comprising a control group in order to
      assess the incidence of the same oral signs in the general population. RESULTS:
      Comparing the two groups, fissured tongue was seen in 33.2% of psoriasis patients
      versus 9.9% of control subjects (P<0.0001). There was thus a highly significant
      (P<0.0001) correlation between geographic tongue and psoriasis (7.7% of psoriasis
      patients versus 1% of controls). In addition, a strong correlation was seen
      between the presence of pustular psoriasis and fissured tongue (83.3% of patients
      with pustular psoriasis versus only 30% of patients with other forms of
      psoriasis). DISCUSSION: Our study shows a strong correlation between psoriasis
      and fissured and geographic tongue, although these features are not pathognomonic
      for the disease. As regards geographic tongue, our results are consistent with
      the data in the literature. However, the prevalence of fissured tongue was
      considerably higher among our patients than in series published to date. These
      two types of sign involving the tongue, and which can occur in all forms of
      psoriasis, appear to be particularly strongly associated with pustular psoriasis.
      Patients are generally unaware of this sign and rarely complain of it.

PMID- 21074653
TI  - [Management of drug reaction with eosinophilia and systemic symptoms (DRESS)].
AB  - OBJECTIVE: The management of drug-induced hypersensitivity syndrome or drug
      reaction with eosinophilia and systemic symptoms (DRESS) is not codified.
      Demonstration of the reactivation of Herpesviruses illustrates the specific
      pathophysiology of this syndrome. Proposals for the management of DRESS were
      elaborated by the cutaneous adverse drug reaction working group of the French
      Society of Dermatology to help with its management. METHODS: From a review of
      literature and the experience of the members of this group, consensual proposals
      were written about diagnostic criteria, tests, treatment options, and follow-up.
      These proposals will need to be validated in prospective studies. RESULTS: A
      decisional tree of treatment options is proposed, based on the severity of
      visceral manifestations. The importance of a rapid withdrawal of the culprit drug
      and of a long-term follow-up is underlined. Treatment will be adapted to the
      clinicobiological status (topical corticosteroid, systemic corticosteroid,
      intravenous gammaglobulins, antivirals).

PMID- 21074654
TI  - [Two cases of baboon-like exanthema in primary parvovirus B19 infection].
AB  - INTRODUCTION: Primary parvovirus B19 infection may present a wide variety of
      dermatological features. We report two cases of parvovirus infection presenting
      as flexural erythema of baboon syndrome induced by various drugs, but associated
      with purpuric or oedematous features. CASE REPORTS: A pregnant 23-year-old woman
      at 39 weeks of amenorrhoea and a 49-year-old woman consulted for flexural
      eruption in a setting of fever. In both cases, clinical examination revealed
      erythematosus rash in the major skin folds, with vesicles and elements of purpura
      in the former patient and bullous oedema in the latter. In both cases, the
      diagnosis of primary parvovirus B19 infection was confirmed by positive PCR
      screening of viral genome and by seroconversion after two weeks. The skin lesions
      regressed spontaneously within several days. DISCUSSION: Although initially
      linked solely with systemic drug toxicity, baboon syndrome has since been
      reported in connection with other allergens (drug reactions, contact dermatitis,
      viral and streptococcal infection). Among these causes, parvovirus B19 infection
      merits particular interest.

PMID- 21074655
TI  - [Polymorphic eruption of pregnancy and acquired hemophilia A].
AB  - BACKGROUND: Acquired haemophilia A (AHA) is a rare and serious disease, and
      instances of association with skin diseases have been described. We report a case
      of postpartum AHA associated with atypical polymorphic eruption of pregnancy
      (PEP). PATIENTS AND METHODS: Following delivery of her second child, a 27-year
      old woman developed a generalised pruritic erythematous papular and vesicular
      rash in plaques. The diagnosis of pemphigoid gestationis was ruled out on the
      basis of negative immunopathology results and a diagnosis of PEP was made.
      Lengthening of activated cephalin time was observed, without correction by
      addition of control plasma, and prothrombin time was normal. AHA was confirmed by
      the very low levels of factor VIII and the presence of antifactor VIII antibody.
      The patient was given intravenous activated recombinant factor VII for epistaxis
      and gingival bleeding, followed by an infusion of polyvalent immunoglobulins and
      systemic corticosteroids. Both diseases regressed within a few weeks. DISCUSSION:
      This case is original in terms of the atypical presentation of AHA associated
      with severe PEP. AHA was associated with the presence of antifactor VIII Ab.
      Although the disease generally occurs alone, it has already been reported during
      pregnancy and the postpartum period, and in association with various forms of
      dermatosis, including bullous pemphigoid, although to our knowledge, never in
      association with PEP or pemphigoid gestationis. However, neither the underlying
      mechanisms of this association of PEP and AHA, which was probably not a chance
      occurrence, nor the risks of relapse of these conditions during subsequent
      pregnancies have been elucidated.

PMID- 21074656
TI  - [Osteoma cutis presenting as an erythematous and grainy, retroauricular plaque].
AB  - BACKGROUND: Authentic bone tissue can be observed in the skin, in both the
      epidermis and dermis, where it produces cutaneous osteomas. These lesions are
      classed as either primary or secondary ossifications. Secondary ossifications are
      the consequence of inflammatory lesions such as acne or injuries while primary
      ossifications are neither preceded by preexisting lesions nor associated with
      other lesions. PATIENTS AND METHODS: A 22-year-old man with no prior history
      consulted for a grainy, erythematous, telangiectatic retroauricular plaque on the
      right side. Palpation revealed hard grainy lesions giving a tactile sensation of
      small stones. Histological analysis showed an ossification in the dermis
      resulting from mature bone in contact with dilated vessels. A diagnosis of venous
      malformation with osseous metaplasia was initially proposed, but the patient
      insisted that no vascular anomaly had preceded the grainy lesions. Further
      histological analysis demonstrated that the vascular anomalies were restricted to
      the ossified regions and the final diagnosis was of primary cutaneous osteoma.
      DISCUSSION: In our patient, the absence of any endocrine anomalies and of any
      vascular malformation supported the diagnosis of primary cutaneous osteoma.
      Certain vascular anomalies such as haemangiomas or venous malformation can lead
      to bone formation. The coexistence in the dermis of osteomas and dilated vessels
      initially led us to suspect osteomas secondary to venous malformation. However,
      the absence of any vascular anomalies preceding the cutaneous osteoma
      contradicted this diagnosis. In venous malformations, phleboliths are usually
      seen as a result of calcium deposits on thrombus rather than authentic osteomas.
      Our patient had no standard primary solitary osteoma of either the nodular or the
      plaque type, and this case thus constitutes a new original form of primary
      cutaneous osteoma.

PMID- 21074657
TI  - [Livedoid erythema of the lower back revealing thrombosed abdominal aortic
      aneurysm].
AB  - BACKGROUND: We report the case of a patient presenting a very painful livedo of
      the lower back as well as paraparesis revealing a complicated abdominal aortic
      aneurysm. PATIENTS AND METHODS: A 61-year-old man was referred to our emergency
      unit for sudden lower back pain and weakness of the lower limbs. He had a large
      and very painful livedo racemosa on the lower back as well as partial
      neurological deficit of the lower limbs. Abdominal CAT revealed a bulky
      thrombosed infrarenal aortic aneurysm. Despite surgery, ischaemia worsened,
      leading to cutaneous then muscular and visceral necrosis, followed by death.
      DISCUSSION: Livedo racemosa of the lower limbs may be the consequence of
      thrombosis or embolism resulting from an abdominal aortic aneurysm. Livedo
      racemosa on other skin areas is uncommon but may be due to the same
      physiopathology. Neurological deficit is occasionally associated with a
      complicated abdominal aortic aneurysm or with surgical treatment thereof.
      However, to our knowledge, livedo on the back associated with neurological
      deficit has not yet been reported. Such an association should prompt
      practitioners to screen for a thrombosed aortic aneurysm. Furthermore, this
      condition is also likely to carry a poor prognosis because of the proximal
      secondary location of the thrombotic phenomenon, involving the lumbar arteries,
      which supply the medullar, cutaneous and muscular arteries.

PMID- 21074658
TI  - [Unilateral acneiform rash in facial palsy].
AB  - BACKGROUND: Cetuximab is a chimeric monoclonal antibody selective for epidermal
      growth factor receptor (EGFR). It is increasingly used in epithelial cancer,
      often in combination with radiotherapy or chemotherapeutic agents, since it
      induces a broad range of cellular responses that enhance tumour sensitivity to
      these therapies. However, it can cause numerous adverse effects, the most common
      being acneiform eruption on the face and trunk, which is generally bilateral and
      symmetric. PATIENTS AND METHODS: Herein we present the first case of unilateral
      cetuximab-induced acneiform eruption in facial palsy. DISCUSSION: To our
      knowledge the medical literature contains no other such cases. Our hypothesis is
      that lymphoedema associated with facial palsy reduces lymphatic drainage,
      promoting the deposition of cetuximab on EGFR and persistence of local signs.

PMID- 21074659
TI  - [Cutaneous necrosis at apomorphine injection points].
AB  - BACKGROUND: Apomorphine is a specific dopaminergic agonist used in the treatment
      of severe fluctuations of Parkinson's disease, particularly in patients on L
      dopa. The drug is usually given subcutaneously, either as several daily
      injections or via a continuous subcutaneous delivery system. We describe two
      cases of localized cutaneous necrosis at the points of subcutaneous apomorphine
      injection. OBSERVATIONS: Two male patients presenting Parkinson's disease were
      treated by subcutaneous injection of apomorphine. One month later, asymptomatic
      necrotic lesions measuring from 2 to 5 mm appeared at the injection sites.
      Complete blood count, standard and advanced coagulation studies and screening
      tests were normal. One patient had taken acetylsalicylic acid. A skin biopsy
      showed normal epidermis, oedema of the papillary dermis with perivascular
      lymphocytic infiltrates, reticular dermal infiltrate with neutrophils, and
      necrosis of the reticular dermis and hypodermis in one patient, and in the other,
      necrosis in the epidermis, dermis, hypodermis and skin appendages, with dermal
      leucocytoclastic vasculitis and cytosteatonecrosis. Due to the severity of
      necrosis, apomorphine was stopped, resulting in improvement of skin lesions in
      one patient. In the second, due to the localized nature of the lesions and the
      improvement in the patient's quality of life since the introduction of
      apomorphine, the drug was continued, resulting in the appearance of new lesions,
      which continued to be limited to the injection sites. COMMENTS: To our knowledge,
      this is the first description of biopsy-proven apomorphine-induced localized skin
      necrosis. Reported cutaneous side effects of the drug include pruritic
      subcutaneous nodules corresponding to panniculitis with large numbers of
      eosinophils, allergic contact dermatitis, pigmented nodules resulting from
      oxidation of apomorphine, and nonspecific rashes. Cutaneous necrosis at injection
      sites could arise through various mechanisms: localized vasoconstriction
      ("dopamine necrosis"), direct toxicity of the injected drug, local manifestations
      of pre-existent coagulation disorders, immunological mechanisms or poor
      administration technique involving intravascular injection. The specific
      pharmacodynamic properties of apomorphine rule out vasomotor phenomena in the
      aetiology of such necrosis. Screening tests for thrombophilia were negative in
      the first patient. Although the underlying mechanism of this form of necrosis
      remains unknown, an immunological mechanism of the immune complex type could be
      considered aetiologically relevant on histological grounds due to the presence of
      vasculitis in one of the two patients.

PMID- 21074660
TI  - [Toxic epidermal necrolysis caused by erroneous substitution of lamotrigine for
      terbinafine].

PMID- 21074661
TI  - [Docetaxel-induced psoriasis].

PMID- 21074662
TI  - [Sweet's syndrome after H1N1 influenza vaccination].

PMID- 21074663
TI  - [Vegetating plates in inguinal folds in pregnancy].

PMID- 21074664
TI  - [Acne and hormonal contraceptives].

PMID- 21074665
TI  - [Darier's disease].

PMID- 21074666
TI  - [Alopecia areata and vitiligo: Can genetics tell us more about their
      mechanisms?].

PMID- 21074667
TI  - [Adult varicella].

PMID- 21074668
TI  - [Diffuse calcinosis in terminal renal failure].

PMID- 21074669
TI  - [Epoetin alpha-induced acute generalized exanthematous pustulosis and
      desensitisation].

PMID- 21074670
TI  - ClearWay Minnesota's(SM) Research Program: a 10-year investment in tobacco
      control. Forward.

PMID- 21074671
TI  - Effects of clean indoor air laws on bar and restaurant revenue in Minnesota
      cities.
AB  - BACKGROUND: In recent years, local governments have strengthened laws to prohibit
      smoking in bars and restaurants to promote patron and employee health. Because of
      concerns that clean indoor air policies could have negative economic effects on
      some hospitality businesses, some cities have adopted partial clean indoor air
      policies (e.g., exempting bars). PURPOSE: This paper considers how partial and
      comprehensive smokefree policies affected bar and restaurant revenue, using
      quarterly data reported to the Minnesota Department of Revenue. METHODS: Data
      from ten Minnesota cities from 2003 to 2007 were used to conduct a time-series
      analysis in 2009, adjusting for the population size of each city. RESULTS: Bars
      and restaurants governed by either partial or comprehensive policies had slightly
      higher revenues than those not regulated by any local clean indoor air policy.
      Bars and restaurants governed by partial local bans reported 0.009% higher total
      revenue (p = 0.5) and 0.052% higher liquor sales revenue (p = 0.003) than those
      not covered by a ban. Bars and restaurants governed by comprehensive local bans
      reported 0.026% higher total revenue (p = 0.05) and 0.018% higher liquor sales
      revenue (p = 0.35). CONCLUSIONS: These findings suggest that smoking bans,
      whether comprehensive or partial, do not have a negative effect on bar and
      restaurant total or liquor revenues and may be associated with slightly higher
      revenue compared to not having a clean indoor air policy.

PMID- 21074672
TI  - Employment change for bars and restaurants following a statewide clean indoor air
      policy.
AB  - BACKGROUND: Clean indoor air policies have been adopted to protect employees in
      all workplaces from exposure to environmental tobacco smoke. Despite numerous
      studies where no significant economic effects were associated with clean indoor
      air policies, concerns persist that such policies will have a severe, negative
      effect on alcohol-licensed businesses. PURPOSE: This study examines the effect of
      a comprehensive, statewide clean indoor air law on bar and restaurant employment
      in Minnesota as a whole, as well as by region in the state. METHODS: Interrupted
      time-series analyses were conducted separately on bar and restaurant employment
      between 2004 and 2008 using data reported by businesses to the Minnesota
      Department of Employment and Economic Development. The statewide clean indoor air
      policy was implemented October 2007; analyses were conducted in 2009. RESULTS:
      After accounting for changes in employment in all other sectors for the state as
      a whole, there were no significant changes in statewide bar or restaurant
      employment associated with the state-level clean indoor air policy. Additionally,
      no significant changes were observed in regional bar or restaurant employment
      following enactment of the clean indoor air policy. CONCLUSIONS: Enactment of a
      comprehensive clean indoor air policy in Minnesota did not result in significant
      changes in bar or restaurant employment in rural or urban regions of the state or
      the state as a whole. In Minnesota, neither bars nor restaurants were associated
      with significant changes in employment following the enactment of a
      comprehensive, statewide clean indoor air policy.

PMID- 21074673
TI  - Short-term effects of a comprehensive, statewide smokefree law on perceived
      opportunities to smoke.
AB  - BACKGROUND: The goal of this study was to assess the effects of Minnesota's
      comprehensive, statewide smokefree law on young adults' perceived opportunities
      to smoke in restaurants and bars. PURPOSE: Differential effects of the law were
      examined for those living with and without previous local smokefree ordinances.
      METHODS: Telephone surveys were conducted 6-12 months prior, 0-6 months prior,
      and 0-6 months after Minnesota's statewide smokefree law went into effect.
      Participants included young adults from a population-based cohort in Minnesota (n
      = 1446) and from four other Upper Midwest states that serve as a comparison (n =
      238). RESULTS: A greater proportion of Minnesota participants (regardless of
      previous law) reported it was very hard for an adult to find a place to smoke in
      both restaurants and bars/clubs after the statewide law, compared to the
      comparison group. Effects were greater among Minnesota participants who did not
      live with a local smokefree ordinance previously. CONCLUSIONS: Within 6 months of
      Minnesota's statewide smokefree law, Minnesota young adults, even those who lived
      with a prior local smoking ordinance, believed it was more difficult for adults
      to find a place to smoke in restaurants and bars/clubs. Changing perceived
      opportunities to smoke in the state may be an initial step in changing social
      norms and smoking behaviors. These results suggest that statewide smokefree laws
      may provide additional barriers to smoking, beyond those obtained through local
      ordinances.

PMID- 21074674
TI  - Change in indoor particle levels after a smoking ban in Minnesota bars and
      restaurants.
AB  - BACKGROUND: Smoking bans in bars and restaurants have been shown to improve
      worker health and reduce hospital admissions for acute myocardial infarction.
      Several studies have also reported improved indoor air quality, although these
      studies generally used single visits before and after a ban for a convenience
      sample of venues. PURPOSE: The primary objective of this study was to provide
      detailed time-of-day and day-of-week secondhand smoke-exposure data for
      representative bars and restaurants in Minnesota. METHODS: This study improved on
      previous approaches by using a statistically representative sample of three venue
      types (drinking places, limited-service restaurants, and full-service
      restaurants), conducting repeat visits to the same venue prior to the ban, and
      matching the day of week and time of day for the before- and after-ban
      monitoring. The repeat visits included laser photometer fine particulate (PM2.5)
      concentration measurements, lit cigarette counts, and customer counts for 19
      drinking places, eight limited-service restaurants, and 35 full-service
      restaurants in the Minneapolis/St. Paul metropolitan area. The more rigorous
      design of this study provides improved confidence in the findings and reduces the
      likelihood of systematic bias. RESULTS: The median reduction in PM2.5 was greater
      than 95% for all three venue types. Examination of data from repeated visits
      shows that making only one pre-ban visit to each venue would greatly increase the
      range of computed percentage reductions and lower the statistical power of pre
      post tests. Variations in PM2.5 concentrations were found based on time of day
      and day of week when monitoring occurred. CONCLUSIONS: These comprehensive
      measurements confirm that smoking bans provide significant reductions in SHS
      constituents, protecting customers and workers from PM2.5 in bars and
      restaurants.

PMID- 21074675
TI  - An evaluation of health benefit modification in Taft-Hartley health and welfare
      funds: implications for encouraging tobacco-cessation coverage.
AB  - BACKGROUND: An estimated one fifth of all U.S. adult smokers receive health
      benefits through insurance plans administered by Taft-Hartley Health and Welfare
      Funds. Most funds do not offer comprehensive tobacco-cessation services to fund
      participants despite evidence that doing so would be cost effective and save
      lives. PURPOSE: This paper examines the decision-making processes of Minnesota
      based fund trustees and advisors to identify factors that influence decisions
      about modifications to benefits. METHODS: Formative data about the process by
      which funds make health benefit modifications were collected in 2007-2008 from 25
      in-depth key informant interviews with fund trustees and a cross-section of fund
      advisors, including administrators, attorneys, and healthcare business
      consultants. Analyses were performed using a general inductive approach to
      identify conceptual themes, employing qualitative data analysis software.
      RESULTS: The most commonly cited factors influencing trustees' decisions about
      health plan benefit modifications-including modifications regarding tobacco
      cessation benefits-were benefit costs, participants' demand for services, and
      safeguarding participants' health. Barriers included information gaps, concerns
      about participants' response, and difficulty projecting benefit utilization and
      success. Advisors wielded considerable influence in decision-making processes.
      CONCLUSIONS: Trustees relied on a small pool of business, legal, and
      administrative advisors to provide guidance and recommendations about possible
      health plan benefit modifications. Providing advisors with evidence-based
      information and resources about benefit design, cost/return-on-investment (ROI),
      effectiveness, and promotion may be an effective means to influence funds to
      provide comprehensive tobacco-cessation benefits.

PMID- 21074676
TI  - Secondhand smoke exposure, awareness, and prevention among African-born women.
AB  - BACKGROUND: Little research exists on exposure to the health risks of secondhand
      smoke among women and children in African immigrant communities. PURPOSE: This
      exploratory study aims to understand the prevalence of secondhand smoke exposure;
      assess levels of awareness of the dangers of secondhand smoke; and identify
      strategies for building increased awareness of these issues in African immigrant
      communities in Minnesota. METHODS: Key informant interviews with ten African
      women community leaders, focus groups with 29 female African youth, and surveys
      of 223 African women were conducted between August 2008 and March 2009. The focus
      groups and key informant interviews were in English, and the surveys were in
      English, French, Oromo, and Somali. RESULTS: Over one quarter of African women
      reported daily exposure to cigarette smoke, and one in ten women reported daily
      exposure to smoke from shisha (fruit-flavored tobacco smoked in a hookah or
      waterpipe). Many respondents had general awareness of the health impacts of
      tobacco smoke, but some were unsure. The majority felt that increased awareness
      was badly needed in their communities. Awareness of the health impacts of shisha
      smoking was particularly low. Strategies for increasing awareness include: using
      media and visual images, attending large gatherings, and appealing to community
      members' priorities, including protecting their children. CONCLUSIONS: Exposure
      to secondhand smoke among women and children in African immigrant communities in
      Minnesota is substantial. Awareness about the health impacts of secondhand smoke
      exposure in these communities needs to be increased. Disseminating visual
      information at existing community gatherings or appealing to individual
      priorities may be the best approaches to increase awareness and motivate change.

PMID- 21074677
TI  - Exploring children's secondhand smoke exposure with early child care providers.
AB  - BACKGROUND: Exposure to secondhand smoke (SHS) is a contributor to the increased
      morbidity and mortality experienced by inner-city African-American children.
      Limited evidence-based programming exists regarding how to address the negative
      effects of SHS in this community. PURPOSE: A collaboration with an early child
      care center provided an opportunity to explore factors related to young
      children's SHS exposure as the first step in developing strategies to reduce
      exposure. METHODS: Survey data were obtained between 2008 and 2009 from 63
      African-American parents of infants and children aged <= 5 years at two early
      child care centers located in an urban Minneapolis neighborhood. Forty-three of
      these children had salivary cotinine levels assessed. RESULTS: Parents living
      below the poverty level were more likely to report that their children were
      regularly exposed to SHS by family/friends (p = 0.01). Sixty-eight percent of
      participants reported complete home smoking restrictions, which was significantly
      correlated with advice from the child's health provider (p = 0.001). Nonsmokers
      and older parents were less likely to receive advice (p = 0.03). Of the 43
      children in whom cotinine levels were assessed, 39.5% had levels > 0.64 ng/ml,
      which suggests high SHS exposure. Lower cotinine levels were significantly
      correlated with living in detached houses. CONCLUSIONS: Exposure to SHS was
      common for children in this study. These findings, if supported by additional
      research, can be used to develop and disseminate targeted health messages about
      childhood SHS sources/negative effects and strategies to reduce exposure.

PMID- 21074678
TI  - Characteristics and prevalence of tobacco use among Somali youth in Minnesota.
AB  - BACKGROUND: Somalis compose the largest African refugee group in the U.S., with
      more than 55,000 primary arrivals since 2000. Minnesota has the largest Somali
      population in the U.S. Despite its size, little research has been conducted to
      determine the extent of tobacco use among Somali youth. PURPOSE: This paper
      reports the results from a knowledge, attitudes, and practices (KAP) survey
      designed to explore factors related to tobacco-use prevention, initiation, and
      cessation, and to reliably estimate tobacco-use prevalence among Somali youth in
      grades 9 through 12 in Minnesota. METHODS: A KAP survey, modeled after validated
      state and national youth tobacco-use surveys, was adapted for Somali youth and
      administered to ethnically Somali youth (N = 302) from seven high schools in
      Minnesota in 2008. Participants were chosen through probability-proportional-to
      size and multi-stage random sampling methods, and the results were analyzed in
      2009. RESULTS: Somali high school students' estimated prevalence for "ever-users"
      of cigarettes was 12.8%, and current use was 4.7%. This is one quarter of the
      reported statewide smoking prevalence for Minnesota high school students (19.1%)
      and half of the nationwide prevalence for blacks/African Americans (11.6%). Ever
      users were more likely to have close friends or live with someone who smoked
      cigarettes (p < 0.01). Belief in the Islamic prohibition of tobacco affected
      future intention to use tobacco (p < 0.01), as did the belief that using
      hookah/sheisha is less risky than smoking cigarettes (p < 0.01). CONCLUSIONS:
      Estimated cigarette use prevalence (4.7%) for Somali youth was substantially
      lower than among Minnesota high school students and also lower than perceived
      prevalence among Somalis. Positive peer pressure and religion appear to be
      protective factors in tobacco use and should be integrated into future Somali
      tobacco prevention and cessation programs, along with education on the risks of
      hookah/sheisha use.

PMID- 21074679
TI  - Smoking-cessation strategies for American Indians: should smoking-cessation
      treatment include a prescription for a complete home smoking ban?
AB  - BACKGROUND: The prevalence of cigarette smoking is particularly high among
      American Indian communities in the Upper Midwest. PURPOSE: To evaluate the
      predictors of smoking cessation among a population-based sample of American
      Indians in the Upper Midwest during a quit attempt aided with nicotine
      replacement therapy (NRT). METHODS: This study used the subsample of American
      Indian adults (n = 291, response rate = 55.4%) from a cohort study of smokers
      engaging in an aided NRT quit attempt. Eligible participants filled an NRT
      prescription between July 2005 and September 2006 through the Minnesota Health
      Care Programs (e.g., Medicaid). Administrative records and follow-up survey data
      were used to assess outcomes approximately 8 months after the NRT fill date. This
      analysis was conducted in 2009-2010. RESULTS: Approximately 33% of American
      Indian respondents trying to quit smoking reported complete home smoking bans.
      Adoption of a complete home smoking ban and greater perceived advantages of NRT
      were cross-sectionally associated with 7-day smoking abstinence in univariate and
      multivariate analyses. Consistent with previous research, older age was a
      significant predictor of 7-day abstinence. Having a history of clinician
      diagnosed anxiety in the past year was associated with decreased likelihood of 7
      day abstinence in the unadjusted analysis, but not significant in multivariate
      analyses. CONCLUSIONS: Results of this study suggest potential modifiable targets
      of interventions for future research to help American Indians quit smoking: (1)
      improved delivery of behavioral interventions to increase the intensity of
      smoking cessation treatment; (2) promotion and adoption of complete home smoking
      bans; and (3) education to increase awareness of the benefits of NRT.

PMID- 21074680
TI  - Smokefree legislation: a review of health and economic outcomes research.
AB  - CONTEXT: Smokefree legislation is a powerful public health intervention. Despite
      progress in smokefree legislation, over half of U.S. adults remain unprotected by
      comprehensive smokefree legislation. EVIDENCE ACQUISITION: This paper reviews the
      scientific literature on health and economic outcome studies of smokefree
      legislation from the past decade, 2000 to early 2010, using MEDLINE and key
      search terms: smoking, smoking cessation, smoking/legislation and jurisprudence,
      smoking cessation/legislation and jurisprudence, and health policy. EVIDENCE
      SYNTHESIS: There is a wealth of research showing the health benefits to entire
      populations when communities implement comprehensive smokefree laws and/or
      regulations. These laws improve the health of hospitality workers and the general
      population by improving indoor air quality, reducing acute myocardial infarctions
      and asthma exacerbations, and improving infant and birth outcomes. Some studies
      report reduced smoking prevalence and cigarette consumption and improved
      cessation outcomes after smokefree legislation. In addition to the health
      benefits, economic studies confirm that smokefree laws do not adversely affect
      business revenues or operating costs. CONCLUSIONS: While there is an abundance of
      smokefree policy outcomes research showing both the health and economic impacts
      of smokefree legislation, these outcomes may have more to do with implementation
      effectiveness than adoption, especially among subpopulations. An emerging body of
      literature documents not only that disparities in health protections remain among
      subpopulations, but that health outcomes of smokefree legislation may vary by
      gender, race/ethnicity, SES, and age. Further research is needed on
      implementation effectiveness of smokefree legislation and differential effects on
      subpopulations.

PMID- 21074681
TI  - Electronic medical records to increase the clinical treatment of tobacco
      dependence: a systematic review.
AB  - CONTEXT: The expanded use of electronic medical records (EMRs) may provide an
      opportunity to increase the use and impact of clinical guidelines to promote
      tobacco-cessation treatment in primary care settings. The objective of this
      systematic review is to evaluate the evidence for such an effect. EVIDENCE
      ACQUISITION: After a systematic search of the English-language literature
      regarding an EMR effect on either smoking cessation or clinician behavior,
      relevant articles were abstracted and findings summarized from both observational
      studies and RCTs. EVIDENCE SYNTHESIS: Of ten identified studies of EMRs and
      tobacco, only two RCTs were found. Adding tobacco status as a vital sign resulted
      in an increase in some clinical guideline recommended actions, particularly
      documentation of smoking status. There was insufficient evidence to quantify the
      effect of an EMR on changes in patient smoking behaviors. CONCLUSIONS: While the
      use of EMRs to prompt or provide feedback on the clinical treatment of tobacco
      dependence demonstrates some promising results, substantial additional research
      is needed to understand the effects of EMRs on provider and patient behavior.

PMID- 21074682
TI  - Reducing the disease burden of tobacco use: the role of health reform and beyond.

PMID- 21074683
TI  - Time to reboot: resetting health care to support tobacco dependency treatment
      services.

PMID- 21074684
TI  - Towards building a neural networks community.

PMID- 21074685
TI  - Immunohistochemical expression of epidermal growth factor receptor, E-cadherin,
      and matrix metalloproteinase-9 in ovarian epithelial cancer and relation to
      patient deaths.
AB  - Ovarian cancer is the most frequent cause of death from gynecologic cancer in the
      world. Current prognostic factors do not allow reliable prediction of response to
      chemotherapy and survival for individual ovarian cancer patients. Epidermal
      growth factor receptor (EGFR), E-cadherin, and matrix metalloproteinase (MMP)-9
      are frequently studied in cancer; but their prognostic value in ovarian carcinoma
      remains unclear. In this study, we investigated the immunohistochemical
      expression of EGFR, E-cadherin, and MMP-9 in 120 cases of ovarian epithelial
      carcinoma; their relation to each other; their relation to histologic type,
      grade, and stage; and their relation to death rates after 3years of follow-up.
      Our results show that EGFR and MMP-9 were overexpressed extensively in high
      grades and advanced stages especially in nonserous carcinomas. E-cadherin was
      gradually lost in advanced cancers. There was a positive relation between the 3
      antibodies and between them and the death rates. There is a strong relationship
      between EGFR and MMP-9, and this relation may occur by affecting E-cadherin. The
      present study provides a rationale for evaluating drugs that target these new
      pathways that may be promising in ovarian cancer treatment.

PMID- 21074686
TI  - CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible-
      diagnostic and histogenetic implications.
AB  - Intraosseous salivary gland carcinomas are extremely rare, comprising only 2% to
      3% of all mucoepidermoid carcinomas (MECs) reported. The t(11;19) translocation
      and its CRTC1/MAML1 fusion transcript have been identified in MEC at different
      sites and are believed to be associated with the development of a subset of these
      tumors. However, the status of the fusion transcript has not been reported in
      intraosseous MEC. Here, we report 3 examples of central MEC of the mandible,
      including a case with a history of primary retromolar MEC. Reverse transcriptase
      polymerase chain reaction and DNA sequencing analyses of the microdissected
      components of these tumors were used for the detection and verification of the
      fusion transcript. We identified, for the first time, the t(11;19) fusion gene
      transcript in central MEC, including in the previous primary retromolar MEC. No
      fusion transcript was detected in the second primary noncentral MEC or in another
      central MEC. The results indicate that central MEC can manifest the fusion
      transcript. This finding may have diagnostic and histogenetic roles in the future
      analysis of this entity.

PMID- 21074687
TI  - Bile duct-like differentiation in teratoma: a clinicopathologic and
      immunohistochemical study.
AB  - The presence of biliary differentiation as part of teratoma is very unusual and
      has been reported only once as part of hepatocellular component; however, its
      incidence and significance were not studied. We reviewed available mixed germ
      cell tumors and pure teratomas for the last 18 years at our institution. Data on
      age, tumor size, location, gross and microscopic findings, proper prior clinical
      history, and outcome were obtained. Histologic components of teratoma were
      evaluated; percentage of bile duct-like structures was calculated, and cases were
      immunohistochemically studied. Forty-five cases were included (19 testicular
      neoplasms, 20 retroperitoneal lymph node resections, 5 mediastinal tumors, and 1
      pulmonary resection), obtained from male patients 15 to 48 years old (mean, 28.8
      years; median, 29 years). Bile duct-like tubules were identified in 11 (24%)
      cases. In 10 cases, the foci of bile duct-like structures represented less than
      1% of the tumor tissue, whereas 1 case was almost exclusively composed of these
      structures. In all the cases, immunostains of bile duct-like tubules were
      positive for cytokeratin 7 and 19 and negative for other markers. Our findings
      show a significant prevalence of bile duct-like structures in teratoma.
      Immunohistochemical studies, although not specific, support a biliary-like
      immunophenotype. The presence of these structures did not adversely affect
      patient's prognosis; however, diagnostic awareness of their existence is
      relevant, as treatment and prognosis may vary significantly between teratomas and
      yolk sac or Sertoli cell tumors.

PMID- 21074688
TI  - Muscularis mucosae versus muscularis propria in gallbladder, cystic duct, and
      common bile duct: smoothelin and desmin immunohistochemical study.
AB  - The muscle layer in the cystic duct and common bile duct is not well defined, and
      it is unresolved whether it represents muscularis mucosae or muscularis propria.
      Smoothelin is a novel smooth muscle-specific contractile protein expressed only
      in fully differentiated smooth muscle cells of the muscularis propria and not in
      proliferative or noncontractile smooth muscle cells of the muscularis mucosae. In
      this study, we characterize the histologic aspects of the muscle layer in
      gallbladder, cystic duct, and common bile duct by evaluation of routine
      histologic sections and the utilization of immunohistochemistry using desmin and
      smoothelin. Formalin-fixed, paraffin-embedded sections of the gallbladder (15
      cases), cystic duct (11 cases), and common bile duct (10 cases) were stained for
      smoothelin and desmin. Staining intensity was evaluated as weak or strong. The
      staining pattern score was evaluated as follows: 0 or negative = less than or
      equal to 5% positivity, +1 or focal = 6% to 10% positivity, +2 or moderate = 11%
      to 50% positivity, and +3 = greater than 50% muscle cells positivity. With
      desmin, strong and diffuse (+3) staining was observed in all gallbladder cases
      (15/15, 100%), highlighting one continuous muscle layer. The muscle layer was
      discontinuous and interrupted in all cystic duct cases and in most common bile
      ducts, highlighted by the desmin stain. Smoothelin intensely stained (at least
      +2) muscle fibers in the gallbladder in 11 (73%) of 15 cases similar to that
      observed with desmin staining. In contrast, common bile ducts predominantly had
      absent or weak and focal immunostaining (0 or +1 staining) with smoothelin (7/10,
      70%), with only a few cases (3/10, 30%) having +2 staining (no cases with +3).
      Cystic ducts also showed absent or weak and focal immunostaining with smoothelin,
      with 5 (44%) of 11 cases showing 2+ immunostaining with smoothelin (no cases with
      3+). Based on our findings, we conclude that, in the gallbladder wall, the muscle
      layer is muscularis propria and there is no muscularis mucosae present. In the
      cystic duct and common bile duct, only an attenuated and incomplete muscle layer
      of muscularis mucosae is present; because there is no muscularis propria, there
      probably is limited contractile function. Differentiating these anatomical muscle
      structures may be important for the pathologic staging of carcinoma in these
      organs.

PMID- 21074689
TI  - Human telomerase reverse transcriptase expression in colorectal tumors:
      correlations with immunohistochemical expression and clinicopathologic features.
AB  - Human telomerase reverse transcriptase (hTERT) proteins in colorectal cancer
      investigated in several studies, but to our knowledge, hTERT expression has not
      been evaluated in all of colorectal tumors, including hyperplastic polyps (HPs),
      adenomas, and carcinomas, on paraffin-embedded tissue sections. The aim of the
      present study is to investigate immunohistochemical hTERT expression and its
      relationship with the clinicopathologic features in a spectrum of colorectal
      tumors. In this study, hTERT expression was determined in HP (n = 20),
      adenomatous polyp (AP) (n = 20), colorectal adenocarcinomas (n = 20), and normal
      mucosa (n = 20) by immunohistochemical method. The findings were correlated with
      the clinicopathologic features. The staining level of hTERT in adenomas and
      carcinomas was significantly higher than in normal tissues (P < .05). There was
      also significant difference between HP and AP (P < .05). Level of hTERT in
      carcinomas was higher than in adenomas, but the difference was of no statistical
      significance (P > .05). There was no significant association of hTERT expression
      in cancerous, precancerous, or normal mucosa related to clinicopathologic
      parameters including age, sex, and size of lesion, (P > .05), but only
      association with histologic grade for carcinoma was found (P < .05). Levels of
      hTERT by immunohistochemistry demonstrated that the expression of hTERT was very
      little in normal mucosa and HP, moderate in AP, and highest in carcinoma.
      Thereby, hTERT expression may use the aggressiveness of the colorectal tumors as
      a marker, but it is not related to clinicopathologic data.

PMID- 21074690
TI  - Epithelial cell adhesion molecule expression in pituitary adenomas: an
      immunohistochemical study.
AB  - An important amount of data correlating the expression of epithelial cell
      adhesion molecule (Ep-CAM) with cellular proliferation and de-differentiation
      could directly contribute to carcinogenesis. The aim of this study is to evaluate
      prognosis relevance of Ep-CAM expression in a group of pituitary adenomas.
      Epithelial cell adhesion molecule, proliferating cell nuclear antigen, and
      microvascular density labeling indices in pituitary adenomas were determined by
      immunohistochemistry on tissue samples obtained from each adenoma after surgery.
      We evaluated 45 adenomas. Sixty-two percent were nonsecretor adenomas and 37.8%
      were secretor tumors. Immunohistochemistry was scored for immunoexpression of Ep
      CAM (cytoplasmic, membrane, and mixed pattern). Proliferating cell nuclear
      antigen and vascular density (CD34) labeling indices were assessed. Statistical
      significance was observed between Ep-CAM cytoplasmic immunoreactions (P = .000)
      and higher proliferating cell nuclear antigen (P = .001) in secretor adenomas
      compared with nonsecretor tumors. Vascular density labeling indices did not show
      statistical significance. Therefore, Ep-CAM could be evaluated to distinguish
      secretor and nonsecretor pituitary adenomas. These suggest that the markers could
      predict the growth potential of individual pituitary adenomas.

PMID- 21074691
TI  - Papillary apocrine metaplasia and columnar cell lesion with atypia: is there a
      shared common pathway?
AB  - Papillary apocrine metaplasia (PAM) and columnar cell lesion with atypia (CCL)
      are considered as candidates of early premalignant breast lesions. In this study,
      we investigated their relationship at the morphological level, as we noticed
      their histologic coexistence and proximity in daily routine. We selected 93
      neoplastic and nonneoplastic cases with both PAM and CCL among 477 breast
      specimens and reevaluated sections by measuring the distance between these
      lesions. Ninety-three (19.4%) of 477 breast specimens contained both PAM and CCL;
      in 73.1% of the cases, the 2 lesions were in continuity with or adjacent to each
      other. Lesions less distant than 1 mm are grouped as "adjoining lesions"; and the
      rest, as "distant lesions." A significant difference (P = .006) was found between
      adjoining ("zero" + "<1 mm") and distant (">= 1 mm") lesions; that is, PAM and
      CCL were much closer in the neoplastic group, especially tumors with low grade,
      high estrogen and progesterone receptor expression, and less lymph node
      metastasis. During the detailed examination of adjoining lesions, some "hybrid
      cells" showing properties of both lesions were encountered. Papillary apocrine
      metaplasia and CCL tend to appear in close contact, especially in neoplastic
      breasts with favorable features. This result implies that PAM and CCL may be
      included in the same pathogenetic pathway despite their distinct
      immunophenotypical properties.

PMID- 21074692
TI  - Uterine tumors resembling ovarian sex cord-stromal tumors: synchronous uterine
      tumors resembling ovarian sex cord-stromal tumors and ovarian sex cord tumor.
AB  - Uterine tumors resembling ovarian sex cord-stromal tumors (UTROSCTs) are very
      rare. In this article, we present 3 cases that manifest classical
      histomorphological features alongside diverse immunohistochemical findings. As a
      distinctive finding, one of the patients had UTROSCT in the uterus and an ovarian
      sex cord tumor, called granulosa cell tumor, in the left ovary, simultaneously.
      Problems in diagnosing such pathologic condition generally arise because of the
      variable histologic picture of UTROSCT and may cause problems for general and
      other nongynecologic surgical pathologists. Immunohistochemically, these tumors
      express different markers that indicate their polyphenotypic origins.

PMID- 21074693
TI  - Hepar lobatum carcinomatosum revealing an occult metastatic lobular carcinoma of
      the breast.
AB  - Hepar lobatum carcinomatosum is an unusual cause of chronic liver failure,
      usually maskerading as cirrhosis. The pathogenesis of this syndrome is unclear.
      We report a case of liver failure revealing an occult lobular carcinoma of the
      breast, which offers the opportunity to gain further insight into the mechanisms
      of this rare cause of chronic liver disease. A 57-year-old woman, without history
      of malignancy, presented with hepatomegaly, ascites and altered liver tests
      (serum transaminase activity >5 N and hyperbilirubinemia). The transjugular liver
      biopsy performed at diagnosis showed an extensive fibrosis, containing scattered
      tumor cells, typical of metastatic lobular carcinoma of the breast. Four months
      later, after discovery of a rectal adenocarcinoma, a laparoscopy was performed;
      peritoneal carcinomatosis was discovered. A surgical biopsy of the liver was
      taken during the procedure: it showed histological features suggestive of chronic
      Budd-Chiari syndrome, with venocentric fibrosis and reversed lobulation.
      Intraluminal invasion of small hepatic veins and sinusoidal obstruction by
      neoplastic cells were observed. A small focus of lobular carcinoma was eventually
      discovered in the left mammary gland. The present case report expands the
      spectrum of clinical presentations associated with hepar lobatum carcinomatosum
      and points out to the importance of vascular injury in the pathogenesis of this
      rare cause of chronic liver disease.

PMID- 21074694
TI  - Idiopathic bronchiolitis with features of diffuse panbronchiolitis in an African
      American patient with hepatitis C virus infection.
AB  - Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory process involving
      respiratory bronchioles, largely restricted to Japanese people and associated
      with HLA Bw54. We report a case of idiopathic bronchiolitis with DPB features in
      an African American with hepatitis C virus infection, correlated with postmortem
      anatomic findings. The 53-year-old patient presented with shortness of breath and
      productive cough. Examination revealed hypercapnic respiratory failure. Lung
      computed tomography showed diffuse centrilobular nodules and branching linear
      opacities, whereas lung biopsy demonstrated diffuse peribronchiolar fibrosis and
      chronic inflammation with bronchiolectasis. He died 37 days postadmission.
      Autopsy revealed numerous bronchiolocentric nodules with bronchiolectasis and
      sheets of foamy macrophages in alveolar septa and spaces. This is a rare example
      of idiopathic bronchiolitis with features of DPB in an hepatitis C virus-infected
      African-American patient. Hepatitis C virus infection is known to be associated
      with extrahepatic pulmonary manifestations, and DPB may be one of these. Early
      diagnosis will allow appropriate treatment and may slow the disease progression.

PMID- 21074695
TI  - Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins
      in a case of ameloblastic fibrosarcoma.
AB  - Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the
      benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only
      68 cases reported in the English literature up to 2009. It is composed of a
      benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant
      mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the
      lesion, little is known about its molecular pathogenesis; therefore, in the
      current study, we sought to evaluate the immunoexpression of Ki67, proliferative
      cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained
      with its benign counterpart, as well as to report a new case of this rare entity
      affecting a 19-year-old female patient. The results obtained revealed that all
      the proteins evaluated were overexpressed in the malignant mesenchymal portion of
      AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative
      factors such as Ki67 and proliferative cell nuclear antigen, in association to
      histopathologic features, may be useful markers for identifying the malignancy
      and that, despite the lack of molecular analysis in the case reported, Bcl-2
      alteration may play a role in AFS pathogenesis.

PMID- 21074696
TI  - Prostatic stromal sarcoma with rhabdoid features.
AB  - Rhabdoid tumors have been reported in many different anatomic sites as an
      aggressive tumor and usually present with a rhabdoid tumor component (a composite
      tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been
      described only once in the prostatic region as a possible epithelial origin.
      Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described
      in the literature. Here, we report a case of a PSS with rhabdoid features. A 31
      year-old man presented with a 4-month history of voiding difficulty and anal
      pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate
      invading rectum and urinary bladder. A needle biopsy was diagnosed as an
      unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant
      chemotherapy were given, followed by radical prostatectomy. The prostatectomy
      specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle
      cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also
      contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor
      component. Both spindle and rhabdoid tumor cells were positive for vimentin,
      CD34, and progesterone receptor and negative for desmin and cytokeratin
      immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor
      recurred in the bladder, and the patient died of sepsis. To the best of our
      knowledge, this is the first case of PSS with rhabdoid features. The tumor showed
      an aggressive clinical behavior with a short-term survival (7 months after
      diagnosis).

PMID- 21074697
TI  - Metastatic adult granulosa cell tumor mimicking a benign pancreatic cyst.
AB  - We report an unusual case of metastatic adult granulosa cell tumor in the head of
      pancreas mimicking a benign pancreatic cyst in a 43-year-old female. Clinically,
      it was considered a benign cyst of the pancreas based on its appearance by
      imaging and that repeated fine-needle aspiration and cytologic examination of
      cystic fluid failed to identify malignant cells. The cyst in her pancreas grew
      slowly during the 15 months of close follow-up. Subsequent drainage and open
      biopsy of the cyst wall established the diagnosis of metastatic adult granulosa
      cell tumor that was confirmed in pancreaticoduodenectomy specimen.
      Immunohistochemical study and clinical history were critical to make the correct
      diagnosis and to differentiate this tumor from other more commonly encountered
      cystic neoplasms of the pancreas.

PMID- 21074698
TI  - Preface: analgesia and pain management.

PMID- 21074699
TI  - Clinical interpretation of pharmacokinetic and pharmacodynamic data in zoologic
      companion animal species.
AB  - The treatment and prevention of pain in zoologic companion animals is difficult
      because of the lack of data available on the safety and efficacy of analgesics.
      Pharmacokinetic (PK)-pharmacodynamic (PD) studies integrate changes in drug
      concentrations and changes in the drug's effect. All experimental studies
      assessing the PDs of analgesics have limitations in animals, but the data
      provided by experimental studies are valuable in designing dosages. Placebo
      controlled, randomized, and blinded clinical trials provide the best PK and PD
      data, but are rarely performed in major veterinary species because of the number
      of animals required for the study, lack of preliminary PK and PD data in a given
      species, species-specific differences in PK and PD, and ethical and toxicologic
      concerns. The usefulness and limitations as well as considerations for
      interpreting PK, PD, and controlled clinical studies are discussed. An example of
      allometric analysis of buprenorphine in mammals is also included.

PMID- 21074700
TI  - Fish analgesia: pain, stress, fear aversion, or nociception?
AB  - The increasing use of fish resources and a greater understanding of aquatic
      animal medicine demands providing evidence-based veterinary care for these
      animals. Because fish are aquatic as well as being pokilothermic, there are
      several unique anatomic and physiologic considerations that must be understood
      when working with these animals. Veterinarians need to adapt methodologies for
      examining, performing diagnostics, and treating fish patients to decrease stress,
      decrease fear, and avoid and/or decrease nociception. This article briefly
      defines stress, reviews and compares fish neuroanatomic pathways associated with
      nociception, discusses behavioral observations, summarizes current use of
      analgesics for fish patients, and concludes with the ongoing controversy
      regarding pain on this topic.

PMID- 21074702
TI  - Pain and nociception in reptiles.
AB  - The ability of reptiles to "feel" pain and the significance of pain or
      nociception on physiologic homeostasis is an exceedingly complex question
      requiring integration of both physiologic and behavioral evidence. Until further
      information is available, it would seem most ethical for veterinarians to assume
      that reptiles are capable of feeling pain, and to treat or manage pain when there
      is reasonable evidence that pain is present. With increased information available
      regarding analgesic use in reptiles and with the heightened awareness of the
      importance of analgesia for zoologic companion animals, it is likely that more
      veterinarians will provide pain relief to their reptile patients.

PMID- 21074701
TI  - Analgesia in amphibians: preclinical studies and clinical applications.
AB  - Preclinical studies of analgesia in amphibians or recommendations for clinical
      use of analgesics in amphibian species are extremely limited. This article
      briefly reviews the issues surrounding the use of analgesics in amphibians,
      starting with common definitions of pain and analgesia when applied to nonhuman
      animals. Nociceptive and endogenous opioid systems in amphibians are reviewed,
      and results of preclinical research on opioid and nonopioid analgesics
      summarized. Recommended opioid and nonopioid analgesics are summarized, and
      practical recommendations made for their clinical use.

PMID- 21074703
TI  - Avian analgesia.
AB  - Avian analgesia is now recognized as a critical component of avian medicine and
      surgery. The need to recognize pain and to provide pain relief is the first step,
      and many anecdotal therapeutic doses have been extrapolated from other companion
      animals. Several published research investigations, using several species of
      birds, have begun to provide avian analgesia therapeutic information for clinical
      application. The challenge is to continue pushing this research forward with
      appreciation that there are approximately 10,000 known species of birds, perhaps
      200 species commonly kept as pets, and that each species has a range of behaviors
      as varied as their species-specific PKs and PDs to each analgesic drug.

PMID- 21074704
TI  - Rodent analgesia.
AB  - Rodents of all species are frequently kept as companion animals, with increasing
      client expectations for the care of their animals. Fortunately, specialist
      veterinary interest and information is now available for treatment of rodents. In
      the field of rodent analgesia particularly, much can be learned from the methods
      developed for preventing and alleviating pain in animals undergoing research
      studies in laboratories throughout the world. This article reviews advances in
      pain detection techniques in rodents and makes recommendations on analgesic
      agents that are available for the alleviation of pain.

PMID- 21074705
TI  - Rabbit analgesia.
AB  - With the increasing popularity of rabbits as household pets, the complexity of
      diagnostic and surgical procedures performed on rabbits is increasing, along with
      the frequency of routine surgical procedures. More practitioners are faced with
      the need to provide adequate analgesia for this species. Preemptive analgesia
      prior to planned surgical interventions may reduce nervous system changes in
      response to noxious input, as well as reduce postoperative pain levels and
      analgesic drug requirements. Concurrent administration of analgesic drugs to
      anesthetized rabbits undergoing painful procedures is warranted both pre- and
      intraoperatively as well as postoperatively. This article discusses the
      neuropharmacologic and pharmacologic aspects of pain in rabbits, and reviews
      current protocols for the use of analgesic drugs.

PMID- 21074706
TI  - Pain management in ferrets.
AB  - The growing popularity of ferrets as pets has created the demand for advanced
      veterinary care for these patients. Pain is associated with a broad range of
      conditions, including acute or chronic inflammatory disease, neoplasia, and
      trauma, as well as iatrogenic causes, such as surgery and diagnostic procedures.
      Effective pain management requires knowledge and skills to assess pain, good
      understanding of the pathophysiology of pain, and general knowledge of
      pharmacologic and pharmacodynamic principles. Unfortunately, scientific studies
      on efficacy, pharmacokinetics, pharmacodynamics, and safety of analgesic drugs in
      the ferret are limited. However, basic rules on the treatment of pain and
      mechanisms of action, safety, and efficacy of analgesic drugs in other species
      can be adapted and applied to pain management in ferrets. This article aims to
      make an inventory of what is known on the recognition of pain in ferrets, what
      analgesic drugs are currently used in ferrets, and how they can be adopted in a
      patient-orientated pain management plan to provide effective pain relief while
      reducing and monitoring for unwanted side effects.

PMID- 21074707
TI  - Tramadol use in zoologic medicine.
AB  - Numerous analgesics are available for use in animals, but only a few have been
      used or studied in zoologic species. Tramadol is a relatively new analgesic that
      is available in an inexpensive, oral form, and is not controlled. Studies
      examining the effect of tramadol in zoologic species suggest that significant
      differences exist in pharmacokinetics parameters as well as analgesic dynamics.
      This article reviews the current literature on the use of tramadol in humans,
      domestic animals, and zoologic species.

PMID- 21074708
TI  - Zoologic companion animal rehabilitation and physical medicine.
AB  - Injury and illness in zoologic companion animals can lead to significant pain and
      debilitation. Recovery can be slow and sometimes frustrating. By augmenting
      recovery from trauma or disease with physical medicine and rehabilitation
      techniques, recovery can be more rapid and complete. Physical medicine
      techniques, such as massage, can augment recovery from a painful injury or
      surgery by reducing edema, improving postoperative ileus, and decreasing anxiety.
      Familiarity with the tools of rehabilitation along with focus on pain management,
      strengthening, and proprioception improve patient care.

PMID- 21074709
TI  - Acupuncture for zoological companion animals.
AB  - Research in complementary and alternative veterinary medicine (CAVM) has
      increased dramatically in recent years. Acupuncture represents the most commonly
      practiced and extensively researched of all the CAVM modalities. Acupuncture is
      considered a valid therapeutic mode of treatment that can be integrated into
      Western veterinary medicine for the treatment of large, small, and zoological
      companion animal patients, especially in the area of analgesia. This article is
      intended to provide a guide for the zoological companion animal practitioner to
      gain a basic understanding of acupuncture and its potential for use in the
      zoological companion animal patient.

PMID- 21074710
TI  - Myosin-II puts the squeeze on asymmetric cell division.
AB  - Asymmetric cell division--where two dissimilar daughter cells are produced-
      relies on asymmetric positioning of the telophase spindle midzone, which
      specifies the cleavage furrow. Ou et al. (2010) now report in Science a mechanism
      of asymmetric midzone positioning driven by a polarized cortical distribution of
      the contractile motor myosin-II.

PMID- 21074711
TI  - Targeting p21 degradation locally.
AB  - Just as the activity of many multifunctional proteins is restricted by
      subcellular localization, so is their regulation. In this issue of Development
      Cell, Starostina et al. identify an E3 ubiquitin ligase, CRL2(LRR1), for the
      cyclin-dependent kinase inhibitor p21 that specifically ubiquitylates cytoplasmic
      p21 to facilitate cell migration.

PMID- 21074712
TI  - Anthrax toxins--roadblocks for exocytic trafficking.
AB  - Anthrax toxins cause vascular dysfunction, in part by perturbing the endothelial
      cell barrier. Reporting in Nature, Guichard et al. shed new light on the
      mechanism by which this occurs and show that anthrax toxins interfere with
      exocytic delivery of cadherins to endothelial cell junctions by antagonizing the
      exocyst complex.

PMID- 21074713
TI  - Feeling UPBEAT about growth: linking ROS gradients and cell proliferation.
AB  - Recent work in animals and plants suggests that reactive oxygen species (ROS)
      control cell proliferation. Reporting in Cell, Tsukagoshi et al. (2010) identify
      UPBEAT1 as a key transcription factor in the regulation of ROS distribution,
      which they find controls the transition between cell proliferation and
      differentiation in the Arabidopsis root.

PMID- 21074714
TI  - Global approaches to identify novel participants that modulate intestinal
      epithelial cell development.
AB  - Combinatorial control of lineage-specific gene expression is commonly mediated by
      suites of diverse transcriptional regulators. In this issue of Developmental
      Cell, Verzi et al. (2010) use an unbiased global and computational approach to
      identify distinct partners and functions of CDX2 in intestinal epithelial cell
      differentiation.

PMID- 21074715
TI  - Tuning in to noise: epigenetics and intangible variation.
AB  - In this special issue of Developmental Cell, we discuss the role of chromatin in
      phenotypic variation as a counterpoint to the reviews on chromatin dynamics in
      development and cancer. We highlight some recent work on the role of chromatin in
      transcriptional noise in yeast and Caenorhabditis elegans and consider the
      implications in understanding intangible variation or developmental noise in
      mammals.

PMID- 21074716
TI  - Interpretation of developmental signaling at chromatin: the Polycomb perspective.
AB  - The Polycomb group (PcG) system represses the transcription of important
      developmental regulators and perpetuates this repression across multiple cell
      divisions. Inputs from outside the cell can influence PcG function by recruiting
      additional chromatin factors to PcG-regulated loci or by downregulating the PcG
      genes themselves. These types of PcG system modulation allow context-dependent
      induction of genes during development, in cancer, and in response to changes in
      the environment. In this review, we outline instances where molecular players in
      this process have been recently identified, comparing and contrasting different
      ways in which derepression is achieved, and projecting directions for future
      research.

PMID- 21074718
TI  - Epigenetic transitions in germ cell development and meiosis.
AB  - Germ cell development is controlled by unique gene expression programs and
      involves epigenetic reprogramming of histone modifications and DNA methylation.
      The central event is meiosis, during which homologous chromosomes pair and
      recombine, processes that involve histone alterations. At unpaired regions,
      chromatin is repressed by meiotic silencing. After meiosis, male germ cells
      undergo chromatin remodeling, including histone-to-protamine replacement. Male
      and female germ cells are also differentially marked by parental imprints, which
      contribute to sex determination in insects and mediate genomic imprinting in
      mammals. Here, we review epigenetic transitions during gametogenesis and discuss
      novel insights from animal and human studies.

PMID- 21074717
TI  - Histone variants in metazoan development.
AB  - Embryonic development is regulated by both genetic and epigenetic mechanisms,
      with nearly all DNA-templated processes influenced by chromatin architecture.
      Sequence variations in histone proteins, core components of chromatin, provide a
      means to generate diversity in the chromatin structure, resulting in distinct and
      profound biological outcomes in the developing embryo. Emerging literature
      suggests that epigenetic contributions from histone variants play key roles in a
      number of developmental processes such as the initiation and maintenance of
      pericentric heterochromatin, X-inactivation, and germ cell differentiation. Here,
      we review the role of histone variants in the embryo with particular emphasis on
      early mammalian development.

PMID- 21074719
TI  - Small RNA-mediated quiescence of transposable elements in animals.
AB  - Transposable elements (TEs) are major components of the intergenic regions of the
      genome. However, TE transposition has the potential to threaten the reproductive
      fitness of the organism; therefore, organisms have evolved specialized molecular
      systems to sense and repress the expression of TEs to stop them from jumping to
      other genomic loci. Emerging evidence suggests that Argonaute proteins play a
      critical role in this process, in collaboration with two types of cellular small
      RNAs: PIWI-interacting RNAs (piRNAs) of the germline and endogenous small
      interfering RNAs (endo-siRNAs) of the soma, both of which are transcribed from
      TEs themselves.

PMID- 21074720
TI  - Aberrant epigenetic landscape in cancer: how cellular identity goes awry.
AB  - Appropriate patterns of DNA methylation and histone modifications are required to
      assure cell identity, and their deregulation can contribute to human diseases,
      such as cancer. Our aim here is to provide an overview of how epigenetic factors,
      including genomic DNA methylation, histone modifications, and microRNA
      regulation, contribute to normal development, paying special attention to their
      role in regulating tissue-specific genes. In addition, we summarize how these
      epigenetic patterns go awry during human cancer development. The possibility of
      "resetting" the abnormal cancer epigenome by applying pharmacological or genetic
      strategies is also discussed.

PMID- 21074721
TI  - Differentiation-specific histone modifications reveal dynamic chromatin
      interactions and partners for the intestinal transcription factor CDX2.
AB  - VIDEO ABSTRACT: Cell differentiation requires remodeling of tissue-specific gene
      loci and activities of key transcriptional regulators, which are recognized for
      their dominant control over cellular programs. Using epigenomic methods, we
      characterized enhancer elements specifically modified in differentiating
      intestinal epithelial cells and found enrichment of transcription factor-binding
      motifs corresponding to CDX2, a critical regulator of the intestine. Directed
      investigation revealed surprising lability in CDX2 occupancy of the genome, with
      redistribution from hundreds of sites occupied only in proliferating cells to
      thousands of new sites in differentiated cells. Knockout mice confirmed distinct
      Cdx2 requirements in dividing and mature adult intestinal cells, including
      responsibility for the active enhancer configuration associated with maturity.
      Dynamic CDX2 occupancy corresponds with condition-specific gene expression and,
      importantly, to differential co-occupancy with other tissue-restricted
      transcription factors, such as GATA6 and HNF4A. These results reveal dynamic,
      context-specific functions and mechanisms of a prominent transcriptional
      regulator within a cell lineage.

PMID- 21074722
TI  - The NF2 tumor suppressor, Merlin, regulates epidermal development through the
      establishment of a junctional polarity complex.
AB  - The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a FERM (Four
      point one, Ezrin, Radixin, Moesin) domain-containing protein whose loss results
      in defective morphogenesis and tumorigenesis in multiple tissues. Like the
      closely related ERM proteins (Ezrin, Radixin, and Moesin), Merlin may organize
      the plasma membrane by assembling membrane protein complexes and linking them to
      the cortical actin cytoskeleton. We previously found that Merlin is a critical
      mediator of contact-dependent inhibition of proliferation and is required for the
      establishment of stable adherens junctions (AJs) in cultured cells. Here, we
      delineate the molecular function of Merlin in AJ establishment in epidermal
      keratinocytes in vitro and confirm that a role in AJ establishment is an
      essential function of Merlin in vivo. Our studies reveal that Merlin can
      associate directly with alpha-catenin and link it to Par3, thereby providing an
      essential link between the AJ and the Par3 polarity complex during junctional
      maturation.

PMID- 21074724
TI  - CRL2(LRR-1) targets a CDK inhibitor for cell cycle control in C. elegans and
      actin-based motility regulation in human cells.
AB  - The Cip/Kip CDK inhibitor (CKI) p21(Cip1/WAF1) has a critical role in the nucleus
      to limit cell proliferation by inhibiting CDK-cyclin complexes. In contrast,
      cytoplasmic p21 regulates cell survival and the actin cytoskeleton. These
      divergent functions for p21 in different cellular compartments suggest the
      necessity for complex regulation. In this study, we identify the CRL2(LRR-1)
      ubiquitin ligase as a conserved regulator of Cip/Kip CKIs that promotes the
      degradation of C. elegans CKI-1 and human p21. The nematode CRL2(LRR-1) complex
      negatively regulates nuclear CKI-1 levels to ensure G1-phase cell cycle
      progression in germ cells. In contrast, human CRL2(LRR1) targets cytoplasmic p21,
      acting as a critical regulator of cell motility that promotes a nonmotile
      stationary cell state by preventing p21 from inhibiting the Rho/ROCK/LIMK
      pathway. Inactivation of human CRL2(LRR1) leads to the activation of the actin
      depolymerizing protein cofilin, dramatic reorganization of the actin
      cytoskeleton, and increased cell motility.

PMID- 21074723
TI  - The Fz-Dsh planar cell polarity pathway induces oriented cell division via
      Mud/NuMA in Drosophila and zebrafish.
AB  - The Frizzled receptor and Dishevelled effector regulate mitotic spindle
      orientation in both vertebrates and invertebrates, but how Dishevelled orients
      the mitotic spindle is unknown. Using the Drosophila S2 cell "induced polarity"
      system, we find that Dishevelled cortical polarity is sufficient to orient the
      spindle and that Dishevelled's DEP domain mediates this function. This domain
      binds a C-terminal domain of Mud (the Drosophila NuMA ortholog), and Mud is
      required for Dishevelled-mediated spindle orientation. In Drosophila, Frizzled
      Dishevelled planar cell polarity (PCP) orients the sensory organ precursor (pI)
      spindle along the anterior-posterior axis. We show that Dishevelled and Mud
      colocalize at the posterior cortex of pI, Mud localization at the posterior
      cortex requires Dsh, and Mud loss-of-function randomizes spindle orientation.
      During zebrafish gastrulation, the Wnt11-Frizzled-Dishevelled PCP pathway orients
      spindles along the animal-vegetal axis, and reducing NuMA levels disrupts spindle
      orientation. Overall, we describe a Frizzled-Dishevelled-NuMA pathway that
      orients division from Drosophila to vertebrates.

PMID- 21074727
TI  - Progress in molecular biology and translational science. development,
      differentiation and disease of the para-alimentary tract. Preface.

PMID- 21074726
TI  - Interplay between the transcription factor Zif and aPKC regulates neuroblast
      polarity and self-renewal.
AB  - How a cell decides to self-renew or differentiate is a critical issue in stem
      cell and cancer biology. Atypical protein kinase C (aPKC) promotes self-renewal
      of Drosophila larval brain neural stem cells, neuroblasts. However, it is unclear
      how aPKC cortical polarity and protein levels are regulated. Here, we have
      identified a zinc-finger protein, Zif, which is required for the expression and
      asymmetric localization of aPKC. aPKC displays ectopic cortical localization with
      upregulated protein levels in dividing zif mutant neuroblasts, leading to
      neuroblast overproliferation. We show that Zif is a transcription factor that
      directly represses aPKC transcription. We further show that Zif is phosphorylated
      by aPKC both in vitro and in vivo. Phosphorylation of Zif by aPKC excludes it
      from the nucleus, leading to Zif inactivation in neuroblasts. Thus, reciprocal
      repression between Zif and aPKC act as a critical regulatory mechanism for
      establishing cell polarity and controlling neuroblast self-renewal.

PMID- 21074725
TI  - Integration of brassinosteroid signal transduction with the transcription network
      for plant growth regulation in Arabidopsis.
AB  - Brassinosteroids (BRs) regulate a wide range of developmental and physiological
      processes in plants through a receptor-kinase signaling pathway that controls the
      BZR transcription factors. Here, we use transcript profiling and chromatin
      immunoprecipitation microarray (ChIP-chip) experiments to identify 953 BR
      regulated BZR1 target (BRBT) genes. Functional studies of selected BRBTs further
      demonstrate roles in BR promotion of cell elongation. The BRBT genes reveal
      numerous molecular links between the BR-signaling pathway and downstream
      components involved in developmental and physiological processes. Furthermore,
      the results reveal extensive crosstalk between BR and other hormonal and light
      signaling pathways at multiple levels. For example, BZR1 not only controls the
      expression of many signaling components of other hormonal and light pathways but
      also coregulates common target genes with light-signaling transcription factors.
      Our results provide a genomic map of steroid hormone actions in plants that
      reveals a regulatory network that integrates hormonal and light-signaling
      pathways for plant growth regulation.

PMID- 21074728
TI  - Transcriptional control of acinar development and homeostasis.
AB  - Pancreatic acinar cells are highly specialized exocrine factories that produce
      copious amounts of digestive enzymes for intestinal digestion. Acinar cells arise
      from a population of multipotent progenitor cells (MPCs) that also produce ductal
      cells, which channel the acinar secretions to the intestine, and endocrine cells,
      which populate the islets of Langerhans. During a final stage of differentiation,
      acinar cells acquire powerful systems for maintaining cellular homeostasis in the
      face of great demands for protein synthesis and energy production. We summarize
      the pancreatic transcription factors that guide pancreatic development through
      the formation of the MPC population, the resolution of acinar, ductal, and islet
      lineages, the initiation of the acinar developmental program, and the completion
      of acinar cell differentiation. We discuss the evidence for the specific roles of
      these factors at each developmental transition and review the plasticity of
      mature acinar cells.

PMID- 21074730
TI  - Transcriptional control of hepatocyte differentiation.
AB  - The liver is the largest glandular organ in the body and plays a central role in
      controlling metabolism. During hepatogenesis, complex developmental processes
      must generate an array of cell types that are spatially arranged to generate a
      hepatic architecture that is essential to support liver function. The processes
      that control the ultimate formation of the liver are diverse and complex and in
      many cases poorly defined. Much of the focus of research during the past three
      decades has been on understanding how hepatocytes, which are the predominant
      liver parenchymal cells, differentiate during embryogenesis. Through a
      combination of mouse molecular genetics, embryology, and molecular biochemistry,
      investigators have defined a myriad of transcription factors that combine to
      control formation and function of hepatocytes. Here, we will review the major
      discoveries that underlie our current understanding of transcriptional regulation
      of hepatocyte differentiation.

PMID- 21074731
TI  - Molecular mechanisms of biliary development.
AB  - The biliary tree drains the bile produced by hepatocytes to the duodenum via a
      network of intrahepatic and extrahepatic ducts. In the embryo, the intrahepatic
      ducts are formed near the branches of the portal vein and derive from the liver
      precursor cells of the hepatic bud, whereas the extrahepatic ducts directly
      emerge from the primitive gut. Despite this dual origin, intrahepatic and
      extrahepatic ducts are lined by a common cell type, the cholangiocyte. In this
      chapter, we describe how bile ducts are formed and cholangiocytes differentiate,
      and focus on the regulation of these processes by intercellular signaling
      pathways and by transcriptional and posttranscriptional mechanisms.

PMID- 21074732
TI  - Molecular determinants of liver zonation.
AB  - The phenomenon of "liver zonation" is a remarkable process by which the liver
      fulfills its metabolic functions, involving highly dynamic transcriptional
      mechanisms. Its understanding is therefore a challenging issue. Zonation is
      reflected in heterogeneity of hepatocytes along the porto-central axis of the
      liver: periportal hepatocytes, located in the vicinity of the afferent portal
      vein, do not express the same metabolic enzymes than pericentral hepatocytes
      located near the efferent central vein. This is mainly dictated at the
      transcriptional level by specific pericentral versus periportal genetic programs.
      The mechanisms by which zonation is established have been extensively
      investigated since its initial discovery 40 years ago. The discovery in 2006 that
      Wnt/beta-catenin pericentral signaling was a master regulator of this complex
      liver topology has been a major breakthrough. A major current priority in the
      field is the integration of the beta-catenin pathway with other determinants that
      govern zonation of the liver.

PMID- 21074733
TI  - Fibrosis in the liver: acute protection and chronic disease.
AB  - The understanding of the cellular and molecular mechanisms of the fibrotic wound
      healing response of the liver has made dramatic progress in the past 20 years.
      Hepatic stellate cells (HSCs), which after liver injury proliferate and
      transdifferentiate to myofibroblasts, have emerged as the primary source of the
      fibrotic response, even though other fibrogenic cells may also contribute to the
      production of extracellular matrix (ECM). Advances in the understanding of HSC
      regulation include apoptotic signaling, angiogenic signaling, and responses to
      oxidative stress. The ECM has emerged not only as a structural scaffold, but also
      as a dynamic and interactive matrix regulating stellate cell activation.
      Additionally, the innate immune system and immune signaling, as well as a
      broadening understanding of the transcriptional regulation including microRNAs
      and epigenetic events offer potential therapeutic targets. Unraveling genetic
      determinants related to mechanisms of hepatic fibrogenesis promise individualized
      therapy or prevention. Hepatic fibrosis and cirrhosis have emerged as treatable
      and potentially reversible consequence of chronic liver disease.

PMID- 21074729
TI  - Molecular biology of pancreatic ductal adenocarcinoma progression: aberrant
      activation of developmental pathways.
AB  - Embryonic development marks a period of peak tissue growth and morphogenesis in
      the mammalian lifecycle. Many of the pathways that underlie cell proliferation
      and movement are relatively quiescent in adult animals but become reactivated
      during carcinogenesis. This phenomenon has been particularly well documented in
      pancreatic cancer, where detailed genetic studies and a robust mouse model have
      permitted investigators to test the role of various developmental signals in
      cancer progression. In this chapter, we review current knowledge regarding the
      signaling pathways that act during pancreatic development and the evidence that
      the reactivation of developmentally important signals is critical for the
      pathogenesis of this treatment-refractory malignancy.

PMID- 21074734
TI  - Hierarchies of transcriptional regulation during liver regeneration.
AB  - The remarkable capacity of the liver to regenerate after severe injury or disease
      has excited interest for centuries. The goal of harnessing this process in
      treatment of liver disease, and the appreciation of the parallels between
      regeneration and tumor development in the liver, remain a major driver for
      research in this area. Studies of liver regeneration as a model system offer a
      view of intricate and precisely timed regulatory pathways that drive the process
      toward completion. Successful regeneration of the liver mass demands a hierarchal
      and well-controlled balance between proliferative and metabolic functions, which
      is orchestrated by signaling and regulation of transcription factors. Control and
      regulation of these cascades of transcriptional activities, necessary for
      induction, renewal, and cessation of liver growth, are the focus of this chapter.

PMID- 21074736
TI  - Signaling networks in human hepatocarcinogenesis--novel aspects and therapeutic
      options.
AB  - Hepatocellular carcinoma (HCC) represents one of the most common human
      malignancies with poor prognosis. Because therapeutic strategies are insufficient
      for most HCC patients, there is a great need to determine the central molecular
      mechanisms and pathways in order to derive novel targets for systemic therapy.
      There is vast evidence that not only the dysregulation of distinct signaling
      cascades, but also their interactions at different levels, affect tumor cell
      function. Through these interactions, the effects of pathways can be increased,
      and even new tumor-supporting qualities acquired that further facilitate HCC
      progression. Although several approaches for the modulation of these relevant
      pathways are under development, future therapeutic strategies should take into
      account that oncogenic stimuli cannot be understood in a monodimensional manner.
      In order to avoid escape mechanisms during therapy, strategies based on
      comprehensive knowledge of the interactive regulatory network in
      hepatocarcinogenesis are necessary.

PMID- 21074738
TI  - Preface: Drugs--how they improve our lives and our patients' lives.

PMID- 21074735
TI  - Biology of the adult hepatic progenitor cell: "ghosts in the machine".
AB  - This chapter reviews some of the basic biological principles governing adult
      progenitor cells of the liver and the mechanisms by which they operate. If
      scientists were better able to understand the conditions that govern stem cell
      mechanics in the liver, it may be possible to apply that understanding in a
      clinical setting for use in the treatment or cure of human pathologies. This
      chapter gives a basic introduction to hepatic progenitor cell biology and
      explores what is known about progenitor cell-mediated liver regeneration. We also
      discuss the putative stem cell niche in the liver, as well as the signaling
      pathways involved in stem cell regulation. Finally, the isolation and clinical
      application of stem cells to human diseases is reviewed, along with the current
      thoughts on the relationship between stem cells and cancer.

PMID- 21074739
TI  - Current and developing methods of patient-controlled analgesia.
AB  - Moderate-to-severe acute postoperative pain is commonly controlled with opioids
      administered via programmable intravenous (IV) patient-controlled analgesia (PCA)
      infusion pumps. Intravenously administered opioids provide effective relief of
      postoperative pain, and IV PCA enables patients to control their level of
      analgesia, which has advantages over nurse-administered approaches, including
      more satisfied patients and improved pain relief. Unfortunately, commonly used
      opioid analgesics can cause significant adverse effects. Furthermore, IV PCA has
      drawbacks, such as device programming errors, system errors, medication errors,
      limitations in patient mobility, and potential for IV tubing kinks, clogging, and
      transmission of infection. The IV route of administration is also characterized
      by a rapid, high peak in analgesic drug concentration followed by rapidly
      decreasing concentrations. Consequently, respiratory depression, excessive
      sedation, and inadequate pain control can occur. Furthermore, the technical
      assembly of an infusion pump is often complex and time-consuming. PCA modalities
      that incorporate superior opioid analgesics, such as sufentanil, and novel
      noninvasive routes of administration offer great promise for enhancing the
      patient and caregiver experience with the use of postoperative PCA.

PMID- 21074740
TI  - Buprenorphine in postoperative pain management.
AB  - Several decades ago, the analgesic properties of buprenorphine were discovered.
      Its approval for the use as an agent for the treatment of opioid abuse has led to
      increasing numbers of patients presenting for surgery on buprenorphine. This
      article describes the challenges, advantages, and disadvantages of the use of
      buprenorphine as an analgesic for postoperative pain in patients with and without
      preoperative maintenance therapy.

PMID- 21074741
TI  - Anesthesia for patients on buprenorphine.
AB  - Opioid abuse is a devastating, costly, and growing problem in the United States,
      and one for which treatment can be complicated by barriers such as access to care
      and legal issues. Only 12% to 15% of the opioid-dependent population is enrolled
      in methadone maintenance programs. A significant breakthrough occurred with
      passage of the Drug Addiction Treatment Act of 2000 (DATA 2000). For the first
      time in approximately 80 years, physicians could legally prescribe opioid
      medications for the treatment of opioid addiction. The opiate, so designated, was
      buprenorphine (Subutex).

PMID- 21074742
TI  - Intravenous acetaminophen.
AB  - Acetaminophen has unique analgesic and antipyretic properties. It is globally
      recommended as a first-line agent for the treatment of fever and pain due to its
      few contraindications. Acetaminophen lacks the significant gastrointestinal and
      cardiovascular side effects associated with nonsteroidal anti-inflammatory drugs
      and narcotics. An intravenous formulation of acetaminophen is available in Europe
      and is currently undergoing extensive clinical development for use in the United
      States. This use may have important implications for management of postoperative
      pain and fever. This review summarizes recent clinical trial experiences with
      intravenous acetaminophen for the treatment of postoperative pain and fever in
      adult and pediatric subjects.

PMID- 21074743
TI  - Advances in perioperative pain management: use of medications with dual analgesic
      mechanisms, tramadol & tapentadol.
AB  - Recovery from ambulatory surgical procedures can be limited by postoperative
      pain. Inadequate analgesia may delay or prevent patient discharge and can result
      in readmission. More frequently, postoperative pain produces discomfort and
      interrupts sleep, contributing to postoperative fatigue. The development of
      effective analgesic regimens for the management of postoperative pain is a
      priority especially in patients with impaired cardiorespiratory, hepatic, or
      renal function. Tramadol and tapentadol hydrochloride are novel in that their
      analgesic actions occur at multiple sites. Both agents are reported to be mu
      opioid receptor agonists and monoamine-reuptake inhibitors. In contrast to pure
      opioid agonists, both drugs are believed to have lower risks of respiratory
      depression, tolerance, and dependence. The Food and Drug Administration has
      approved both drugs for the treatment of moderate-to-severe acute pain in adults.
      This article provides an evidence-based account of the role of tramadol and
      tapentadol in modern clinical practice.

PMID- 21074744
TI  - Anticoagulants: newer ones, mechanisms, and perioperative updates.
AB  - With a growing number of new anticoagulant/antiplatelet agents being developed,
      it is likely that an increasing number of patients taking these drugs will
      present for surgery and other procedures. A familiarity with mechanisms of action
      and drug interactions helps to maintain optimal patient safety in the
      perioperative period. Furthermore, it is crucial for anesthesiologists to remain
      current on recommendations regarding discontinuation or need to continue the
      newer anticoagulants/antiplatelet drugs in patients presenting for surgery and/or
      regional anesthesia. Further studies are needed for monitoring of many of these
      newer agents and to identify antidotes.

PMID- 21074745
TI  - Recombinant factor VIIa in trauma patients without coagulation disorders.
AB  - Recombinant activated factor VIIa (rFVIIa) has many clinical applications for
      patients with congenital bleeding disorders and in a variety of clinical
      settings. Additional studies in the future are ongoing and should provide the
      clinical anesthesiologist an additional option during certain bleeding states.
      Specific recommendations as to timing of administration and frequent monitoring
      of ionized calcium status are suggested at this time. Optimization of fibrinogen
      levels, platelet levels, pH, and body temperature will enhance efficacy of
      rFVIIa.

PMID- 21074746
TI  - Sugammadex: cyclodextrins, development of selective binding agents, pharmacology,
      clinical development, and future directions.
AB  - Neuromuscular blocking agents are widely used in perioperative medicine to aid in
      endotracheal intubation, facilitate surgery, and in critical care/emergency
      medicine settings. Muscle relaxants have profound clinical uses in current
      surgical and intensive care and emergency medical therapy. This article reviews
      cyclodextrins, development of selective binding agents, clinical development, and
      future directions of sugammadex.

PMID- 21074747
TI  - Dexmedetomidine: clinical application as an adjunct for intravenous regional
      anesthesia.
AB  - The selective alpha-2 adrenoceptor agonist, dexmedetomidine, has been shown to be
      a useful, safe adjunct in perioperative medicine. Intravenous regional anesthesia
      is one of the simplest forms of regional anesthesia and has a high degree of
      success. However, intravenous regional anesthesia is limited by the development
      of tourniquet pain and its inability to provide postoperative analgesia. To
      improve block quality, prolong postdeflation analgesia, and decrease tourniquet
      pain, various chemical additives have been combined with local anesthetics,
      although with limited success. The antinociceptive effects of alpha-2
      adrenoceptor agonists have been shown in animals and in humans. However, less is
      known about the clinical effects of dexmedetomidine when coadministered with
      local anesthetics in patients undergoing intravenous regional anesthesia. This
      review examines what is currently known to improve our understanding of the
      properties and application of dexmedetomidine when used as an adjunct in
      intravenous regional anesthesia.

PMID- 21074748
TI  - Cardiovascular pharmacology: an update.
AB  - Cardiovascular diseases are a leading cause of hospitalizations and death in the
      United States and elsewhere in the world. Developing new therapeutic agents for
      cardiovascular diseases has always been the priority for the pharmaceutical
      industry because of the huge potential market for these drugs. Some of these
      newer drugs are frequently used in the practice of cardiovascular anesthesiology.
      This article reviews the recent advances in cardiovascular medications related to
      the practice of cardiac anesthesia.

PMID- 21074749
TI  - Perioperative statin use: an update.
AB  - HMG CoA reductase inhibitors (statins) are a proven modality to reduce serum
      cholesterol and have been shown to reduce morbidity and mortality in
      cardiovascular patients. Statins have also demonstrated improvements in
      postoperative outcomes among patients taking them in the perioperative period.
      Many of the studies are limited to select patient populations and/or select
      surgeries. This review will give an overview of the pharmacology of statins,
      summarize the mechanisms of the beneficial effects of statins, and provide an
      overview of evidence in the use of statins in the perioperative period.

PMID- 21074750
TI  - Levosimendan: calcium sensitizer and inodilator.
AB  - Levosimendan is a unique therapeutic agent that decreases mortality in acute
      episodes of decompensated heart failure by increasing myocardial contractility
      without increasing oxygen consumption or ATP demands, decreasing preload, or
      decreasing afterload. The mechanism for each accomplishment is novel. The drug is
      a calcium sensitizer, which increases myocyte contractility by stabilizing
      troponin C rather than by increasing intracellular calcium. The drug may have
      implications in numerous other common and chronic medical ailments, even in
      overdoses of drugs that stun and depress the myocardium.

PMID- 21074751
TI  - Molecular approaches to improving general anesthetics.
AB  - Over the last several decades, the average age of patients has steadily
      increased, whereas the use of general anesthesia and deep sedation has grown
      largely outside the operating room environment. Currently available general
      anesthetics and delivery models represent limitations in addressing these trends.
      At the same time, research has tremendously expanded the knowledge of how general
      anesthetics produce their beneficial effects and also revealed evidence of
      previously unappreciated general anesthetic toxicities. The goal of this review
      is to highlight these important developments and describe translational research
      on new general anesthetics with the potential to improve and reshape clinical
      care.

PMID- 21074752
TI  - Efficacy of an early intervention based on acceptance and commitment therapy for
      adults with depressive symptomatology: Evaluation in a randomized controlled
      trial.
AB  - OBJECTIVE: The current study examined the efficacy of an early intervention based
      on acceptance and commitment therapy (ACT) for depressive symptomatology. The ACT
      intervention is aimed at increasing the acceptance of negative thoughts and
      emotions and living a mindful and value-based life. METHOD: Adults with mild to
      moderate depressive symptomatology were randomly assigned to the ACT intervention
      (n=49) or to a waiting list (n=44). The mean age of the participants was 49
      years. The majority of the participants was female and of Dutch origin. All the
      participants completed measures before and after the intervention, as well as
      three months later at follow-up to assess depression (CES-D), anxiety (HADS-A),
      fatigue (CIS), alcohol use and acceptance (AAQ-II). RESULTS: The ACT intervention
      led to statistically significant reduction in depressive symptomatology (Cohen's
      d=.60). These reductions were maintained at the three-month follow-up. Also
      significant reductions in anxiety and fatigue were observed. Moreover,
      mediational analysis showed that the improvement of acceptance during the
      intervention mediated the effects of the intervention on depressive
      symptomatology at follow-up. CONCLUSION: These findings suggest that an early
      intervention based on ACT, aimed at increasing acceptance, is effective in
      reducing depressive symptomatology.

PMID- 21074753
TI  - The structure of the Escherichia coli O148 lipopolysaccharide core region and its
      linkage to the O-specific polysaccharide.
AB  - Recently it was demonstrated that Shigella dysenteriae type 1, a cause of severe
      dysentery epidemics, gained its O-specific polysaccharide (O-SP) from Escherichia
      coli O148. The O-SPs of these bacteria differ only by a galactose residue in the
      repeat unit of S. dysenteriae type 1 in place of a glucose residue in E. coli
      O148. Herein, we analyzed the core structure and its linkage to the O-SP in E.
      coli O148 LPS. Both were found to be identical to those of S. dysenteriae type 1
      structures, further supporting the relatedness of these two bacteria. The
      following structure of the core with one repeat unit of the O-SP has been
      assigned (all have d-configuration except l-Rha):

PMID- 21074755
TI  - Vitamin C-treated murine bone marrow-derived dendritic cells preferentially drive
      naive T cells into Th1 cells by increased IL-12 secretions.
AB  - Vitamin C has been reported to shift immune responses toward Th1. In this study,
      we evaluated whether this effect was by way of dendritic cells. Murine dendritic
      cells (DCs) were prepared from bone marrow precursors. DCs treated with vitamin C
      secreted an increased amount of IL-12p70 after activation with LPS. These cells
      rendered naive T cells to secrete more Th1 cytokine, IFN-gamma, and less Th2
      cytokine, IL-5 in the culture supernatants. Vitamin C-treatment also increased
      phosphorylation of p38 and ERK1/2 in DCs. p38 inhibitor in culture media
      suppressed the effect of vitamin C to elevate IL-12p70 secretion. In contrast,
      ERK inhibitor elevated IL-12p70 secretion. In summary, vitamin C taken up into
      DCs increased IL-12p70 secretion of these cells by modulating the activation of
      signal molecules, and thus shifted immune responses toward Th1. These data
      provide us a new insight on the role of vitamin C in modulating immune responses.

PMID- 21074756
TI  - Integrating spatial fuzzy clustering with level set methods for automated medical
      image segmentation.
AB  - The performance of the level set segmentation is subject to appropriate
      initialization and optimal configuration of controlling parameters, which require
      substantial manual intervention. A new fuzzy level set algorithm is proposed in
      this paper to facilitate medical image segmentation. It is able to directly
      evolve from the initial segmentation by spatial fuzzy clustering. The controlling
      parameters of level set evolution are also estimated from the results of fuzzy
      clustering. Moreover the fuzzy level set algorithm is enhanced with locally
      regularized evolution. Such improvements facilitate level set manipulation and
      lead to more robust segmentation. Performance evaluation of the proposed
      algorithm was carried on medical images from different modalities. The results
      confirm its effectiveness for medical image segmentation.

PMID- 21074754
TI  - Potentiation of Th17 cytokines in aging process contributes to the development of
      colitis.
AB  - Th17 cells, which produce IL-17 and IL-22, promote autoimmunity in mice and have
      been implicated in the pathogenesis of autoimmune/inflammatory diseases in
      humans. However, the Th17 immune response in the aging process is still not
      clear. In the present study, we found that the induction of IL-17-producing
      CD4(+) T cells was significantly increased in aged individuals compared with
      young healthy ones. The mRNA expression of IL-17, IL-17F, IL-22, and RORC2 was
      also significantly increased in aged people. Similar to humans, Th17 cells as
      well as mRNAs encoding IL-17, IL-22 and RORgammat were dramatically elevated in
      naive T cells from aged mouse compared to young ones. In addition, CD44 positive
      IL-17-producing CD4(+) T cells were significantly higher in aged mice, suggesting
      that memory T cells are an important source of IL-17 production. Furthermore, the
      percentage of IL-17-producing CD4(+) T cells generated in co-culture with
      dendritic cells from either aged or young mice did not show significant
      differences, suggesting that dendritic cells do not play a primary role in the
      elevation of Th17 cytokines in aged mouse cells. Importantly, transfer of
      CD4(+)CD45Rb(hi) cells from aged mice induced more severe colitis in RAG(-/-)
      mice compared to cells from young mice, Taken together, these results suggest
      that Th17 immune responses are elevated in aging humans and mice and may
      contribute to the increased development of inflammatory disorders in the elderly.

PMID- 21074757
TI  - [Dabigatran induced exanthema].

PMID- 21074758
TI  - Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to
      fertility centers within the United States.
AB  - OBJECTIVE: To determine age-specific serum anti-Mullerian hormone (AMH) values
      for women presenting to U.S. fertility clinics. DESIGN: Retrospective study.
      SETTING: Single clinical reference laboratory. PATIENT(S): A total of 17,120
      women of reproductive age ranging from 24 to 50 years old. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Determination of single-year median and mean AMH values
      with SDs. RESULT(S): Single-year-specific median, mean, and SD values are
      summarized in Table 1. Both median and mean AMH values decreased steadily in a
      manner highly correlated with advancing age. The average yearly decrease in the
      median serum AMH value was 0.2 ng/mL/year through age 35 and then diminished to
      0.1 ng/mL/year after age 35. The rate of decline in mean AMH values was 0.2
      ng/mL/year through age 40 and then diminished to 0.1 ng/mL/year thereafter.
      CONCLUSION(S): Median and mean AMH levels decreased steadily with increasing age
      from 24 to 50 years of age. Such data may be of value to physicians and their
      patients who are considering reproductive options.

PMID- 21074759
TI  - Endoscopic removal of an impacted root canal needle in the jejunum using double
      balloon enteroscopy.

PMID- 21074760
TI  - Albumin and C-reactive protein levels predict short-term mortality after
      percutaneous endoscopic gastrostomy in a prospective cohort study.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a procedure with many
      complications that sometimes can be devastating. To give better advice to
      patients referred for PEG regarding risk of complications, important risk factors
      should be known. OBJECTIVE: To evaluate whether age, body mass index, albumin
      levels, C-reactive protein (CRP) levels, indication for PEG, and comorbidity
      influence the risk of mortality or peristomal infection after PEG insertion.
      DESIGN: Prospective cohort study from 2005 to 2009. Follow-up 14 days after PEG.
      SETTING: University hospital. PATIENTS: This study involved 484 patients referred
      for PEG. INTERVENTION: PEG. MAIN OUTCOME MEASUREMENTS: Mortality within 30 days
      and peristomal infection within 14 days after PEG insertion. All risk estimates
      were calculated with 95% CIs and adjusted for confounding. RESULTS: Among 484
      patients, 58 (12%) died within 30 days after PEG insertion. Albumin <30 g/L
      (hazard ratio [HR], 3.46; 95% CI, 1.75-6.88), CRP >=10 (HR, 3.47; 95% CI, 1.68
      7.18), age >=65 years (HR, 2.26; 95% CI, 1.20-4.25) and possibly body mass index
      <18.5 (HR, 2.04; 95% CI, 0.97-4.31) were associated with increased mortality.
      Patients with a combination of low albumin and high CRP levels had a mortality
      rate of 20.5% compared with 2.6% among patients with normal values, rendering an
      over 7-fold increased adjusted risk of mortality (HR, 7.45; 95% CI, 2.62-21.19).
      LIMITATIONS: Missing data in some study variables. Although the sample size was
      large, weaker associations could not be established. CONCLUSION: The combination
      of low albumin and high CRP levels indicates a substantially increased short-term
      mortality risk after PEG, which should be considered in decision making.

PMID- 21074761
TI  - Predictors of endoscopic treatment outcomes in the management of biliary problems
      after liver transplantation at a high-volume academic center.
AB  - BACKGROUND: Biliary tract problems are the most common complications after liver
      transplantation. ERCP is increasingly being used to address posttransplantation
      biliary problems. OBJECTIVE: To identify predictors of endoscopic treatment
      outcomes in the management of post-liver transplantation complications. SETTING
      AND PATIENTS: All adult patients who underwent liver transplantation at the
      University of California, San Francisco between January 1999 and December 2008
      were reviewed. DESIGN: A multivariate regression analysis. MAIN OUTCOME
      MEASUREMENTS: Identification of donor and recipient factors as well as technical
      considerations that predicted success or failure in the endoscopic management of
      posttransplantation biliary complications. RESULTS: In 1062 patients who
      underwent liver transplantation, there were 224 biliary complications. ERCP was
      the primary treatment modality and was successful in the majority of patients
      treated. Patients with biliary complications who had take-back surgery for a
      nonbiliary indication during the first month after liver transplantation (odds
      ratio [OR], 0.32; P = .03), particularly for bleeding (OR, 0.18; P = .02), were
      less likely to respond to endoscopic therapy. Those who received a graft from a
      donor after cardiac death (OR, 0.15; P = .02) or a living donor (OR, 0.11; P <
      .01) were also less likely to respond to endoscopic therapy. Take-back surgery
      for a nonbiliary indication in the first month after liver transplantation was
      also identified as a novel risk factor for the development of biliary
      complications (OR, 1.80; P = .02). LIMITATIONS: Retrospective design.
      CONCLUSIONS: ERCP can be used to treat the majority of posttransplantation
      biliary problems. However, endoscopic therapy is less efficacious in the
      treatment of complications associated with ischemia.

PMID- 21074762
TI  - Evaluation of a new multitasking platform for endoscopic full-thickness
      resection.
AB  - BACKGROUND: The advent of natural orifice transluminal endoscopic surgery (NOTES)
      has accelerated the development of new technology in the field of GI endoscopy.
      Various suturing devices or multitasking platforms are expected to be valuable
      for endoluminal surgery as well as for NOTES. OBJECTIVE: To evaluate a new
      multitasking platform in performing endoscopic full-thickness resection (EFTR).
      DESIGN: Bench-top comparison study. SETTING: Research laboratory study of 10 ex
      vivo porcine models. INTERVENTION: Ten EFTRs (5 with a double-channel endoscope
      vs 5 with a new multitasking platform) assisted with percutaneous gastric
      lifting. Each group was given the task of resecting a full-thickness specimen of
      the gastric wall including a pseudolesion 10 mm in diameter with an effective
      margin. MAIN OUTCOME MEASUREMENTS: Outcome measurements included time to perform
      the procedure, accuracy of the resection, and efficiency for the task. Accuracy
      was assessed according to variability of the surgical margin and misalignment
      between the mucosal layer and the seromuscular layer. Efficiency was assessed
      according to the duty ratio, which is the percentage of time spent for the main
      purposes compared with the total procedure time. RESULTS: Mean diameter of the
      specimen was not significantly different between the groups. All other assessment
      items were significantly superior in group B to those in group A (P < .05).
      LIMITATIONS: Ex vivo animal model study. CONCLUSION: We were able to perform EFTR
      procedures precisely and effectively by using a new multitasking platform
      compared with use of a conventional endoscope in a porcine model. A multitasking
      platform developed for NOTES procedures would be useful for advanced endoluminal
      surgery such as endoscopic submucosal dissection or EFTR as well as NOTES.

PMID- 21074763
TI  - Spontaneous gastrosplenic fistula secondary to diffuse large B-cell lymphoma.

PMID- 21074764
TI  - Multiple metastases to the pancreas from primary maxillary osteosarcoma:
      diagnosis with EUS-guided FNA.

PMID- 21074765
TI  - Photodynamic therapy for large superficial squamous cell carcinoma of the
      esophagus.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been found to be safe and effective in
      patients with small early esophageal squamous cell carcinoma (SCC). However, its
      efficacy for widespread superficial SCC has not yet been confirmed. OBJECTIVE: To
      assess the long-term survival, complications, and recurrence of PDT for large
      superficial esophageal SCC. DESIGN: Retrospective study. SETTING: Tertiary
      referral center. PATIENTS: A total of 38 patients with superficial SCC of the
      esophagus. All patients had a large unifocal lesion or multifocal lesions that
      were too large to be resected endoscopically. In addition, all patients were
      physiologically unfit for esophagectomy or had refused surgery. INTERVENTIONS:
      PDT with porfimer sodium. MAIN OUTCOME MEASUREMENTS: Clinical follow-up, long
      term survival, complications, and recurrence were evaluated. RESULTS: Thirty-one
      patients (82%) had mucosal cancer (T1m), and 7 (18%) had submucosal cancer
      (T1sm). No patient had lymph node involvement. Nineteen patients had other
      primary malignancies. Complete remission was achieved in 33 (87%). At the time of
      writing, 28 patients (74%) were alive without recurrence. After a median follow
      up period of 64 months (range, 7-125 months) after PDT, the overall 5-year
      survival rate was 76%. There was no treatment-related mortality. LIMITATIONS:
      Retrospective study with a small number of patients. CONCLUSIONS: This long-term
      follow-up study revealed that PDT was a potentially curative treatment for large
      superficial esophageal SCC. PDT might be a reasonable alternative to
      esophagectomy or to endoscopic resection for patients with superficial SCC of the
      esophagus without lymph node metastasis.

PMID- 21074766
TI  - A rare endoscopic finding of GI stromal tumor.

PMID- 21074767
TI  - Detection of stator winding faults in induction motors using three-phase current
      monitoring.
AB  - The objective of this paper is to propose a new method for the detection of inter
      turn short circuits in the stator windings of induction motors. In the previous
      reported methods, the supply voltage unbalance was the major difficulty, and this
      was solved mostly based on the sequence component impedance or current which are
      difficult to implement. Some other methods essentially are included in the
      offline methods. The proposed method is based on the motor current signature
      analysis and utilizes three phase current spectra to overcome the mentioned
      problem. Simulation results indicate that under healthy conditions, the rotor
      slot harmonics have the same magnitude in three phase currents, while under even
      1 turn (0.3%) short circuit condition they differ from each other. Although the
      magnitude of these harmonics depends on the level of unbalanced voltage, they
      have the same magnitude in three phases in these conditions. Experiments
      performed under various load, fault, and supply voltage conditions validate the
      simulation results and demonstrate the effectiveness of the proposed technique.
      It is shown that the detection of resistive slight short circuits, without
      sensitivity to supply voltage unbalance is possible.

PMID- 21074768
TI  - Fracture healing after reamed and unreamed intramedullary nailing in sheep tibia.
AB  - Intramedullary nailing is a well-established method for stabilisation of long
      bone shaft fractures. It is still a controversy as to whether the procedure
      should be done by an unreamed or reamed technique. In the present animal study,
      24 sheep were treated with intramedullary nailing. Midshaft fractures
      (Arbeitsgemeinschaft fur Osteosynthese (AO) type 42-A2/3) were created. Eight
      sheep were treated with an unreamed nailing technique (UN), a further eight sheep
      underwent tibia nailing by the reamed technique using the conventional AO reaming
      system (RC) and in a further eight sheep, reamed nailing was performed using an
      experimental reaming system (RE). Intra-operatively, the intramedullary pressure
      was measured and, during a healing time of 10 weeks, the growth of callus
      formation was labelled with fluorescence markers after 4 and 6 weeks. After 10
      weeks, the animals were euthanised and the quality of fracture healing was
      determined by recording stiffness in torsion, antero-posterior and mediolateral
      bending and the load at yield. In addition, the callus formation at the fracture
      zone was evaluated by fluorescence microscopy and macroradiographs. The results
      showed a decrease of intramedullary pressure when reamed nailing was performed
      with the RE (72.5 mmHg) system compared with the conventional AO reaming system
      (227 mmHg). Mechanical testing did not reveal any significant differences either
      for torsional or bending stiffness or for load at yield for any of the three
      procedures. Histological evaluation showed a similar callus formation for the UN
      group and the RE group. Callus formation in the UN (65 mm(2)) and RE (63 mm(2))
      groups showed a higher increase during the first 6 weeks than those treated with
      the conventional AO reaming system (27 mm(2)). This means that, especially during
      the first weeks of fracture healing, damage to the bone by the reaming process
      can be reduced by reaming with a reaming device with lowered cutting flutes and
      smaller drive-shaft diameter. Intramedullary pressure can be significantly
      reduced by using reaming systems with reduced drive-shaft diameters and deepened
      cutting flutes. In the early phase of fracture healing, callus formation can be
      influenced positively when using the RE system.

PMID- 21074769
TI  - Leptin upregulates caveolin-1 expression: implications for development of
      atherosclerosis.
AB  - OBJECTIVE: To determine the role of hyperleptinemia on caveolin-1 expression and
      leptin signaling. METHODS: Endothelial cells are critical to atherosclerosis
      development; therefore we investigated hyperleptinemia in cultured vascular
      endothelial cells. Dose-dependent effect of leptin on caveolin-1 expression was
      determined by Western blot analysis. Also, the consequence of increased caveolin
      1 expression on leptin signaling was investigated by adenovirus mediated caveolin
      1 overexpression. The effect of increased caveolin-1 expression on leptin
      dependent activation of ERK1/2 and eNOS was determined by Western blot analysis.
      RESULTS: Leptin upregulates caveolin-1 protein expression in a dose dependent
      manner and increased caveolin-1 expression impairs leptin signaling. CONCLUSIONS:
      Leptin increases caveolin-1 protein expression which impairs leptin signaling in
      vascular endothelial cells. Our study identifies an additional leptin mediated
      proatherogenic mechanism and a novel caveolin-1 dependent leptin feedback
      mechanism which may have implications for development of peripheral leptin
      resistance in the endothelium.

PMID- 21074770
TI  - Arterial endothelial function and wall thickness in familial hypercholesterolemia
      and familial combined hyperlipidemia and the effect of statins. A systematic
      review and meta-analysis.
AB  - BACKGROUND: To evaluate the impact of familial hypercholesterolemia (FH) and
      familial combined hyperlipidemia (FCH) on arterial properties and the effects of
      statins. METHODS: We meta-analyzed 51 studies providing data for 4,057 FH
      patients and 732 FCH patients with random-effects models, meta-regression
      analysis and publication bias analysis. The main outcomes of interest were (1)
      brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT),
      and (3) change of IMT and FMD after treatment with statins. RESULTS: Compared to
      normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): 
      5.31%, 95% CI -7.09 to -3.53%, P<0.001] and higher carotid IMT (pooled MD:
      0.12mm, 95% CI 0.09-0.15mm, P<0.001) and femoral IMT (pooled MD: 0.35mm, 95% CI
      0.18-0.51mm, P<0.001). FCH patients had lower FMD and increased IMT (pooled MD: 
      3.60%, 95% CI -6.69 to -0.50%, P=0.023; and 0.06mm, 95% CI 0.04-0.08mm, P<0.001,
      respectively). Total and LDL-cholesterol was a significant determinant of FMD and
      carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH
      patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86-7.92%,
      P<0.001) and decreased carotid IMT (pooled MD of change: -0.025mm, 95% CI -0.042
      to -0.009mm, P=0.003). Changes of both FMD and IMT with statins correlated with
      the duration*treatment intensity product in FH patients (both P<0.01).
      Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%,
      95% CI 0.43-3.69%, P=0.013). No significant publication bias was detected.
      CONCLUSION: Arterial properties are impaired in subjects with FH or FCH. Statins
      improve arterial function and structure in FH patients in a treatment intensity
      related manner.

PMID- 21074771
TI  - Age and coumarin-type anticoagulation are associated with the occurrence of
      intraplaque hemorrhage, while statins are associated less with intraplaque
      hemorrhage: a large histopathological study in carotid and femoral plaques.
AB  - INTRODUCTION: Intraplaque hemorrhage (IPH) is an important determinant of
      progression and destabilization of atherosclerotic plaque. We recently
      demonstrated that IPH is an independent predictor of future cardiovascular events
      after carotid endarterectomy. Thus far, it is unknown whether clinical patient
      characteristics, such as medication use, are associated with the occurrence of
      IPH. The purpose of this study was to examine the association of IPH with
      clinical patient characteristics. METHODS AND RESULTS: 1070 consecutive patients
      who underwent a carotid (n=794) or femoral (n=276) endarterectomy were included.
      Endarterectomy specimens were subjected to histopathological examination. IPH was
      observed in 644/794 (81%) carotid and 175/276 (63%) femoral plaques. Carotid IPH
      was positively correlated with advanced age (69 years [IQR: 62-75] vs. 65 years
      [IQR: 57-73]; P=0.002) and coumarin-type anticoagulation use prior to operation
      (104/116 [90%] with coumarin derivatives vs. 540/678 [80%] without coumarin
      derivatives; P=0.01). Carotid IPH was less frequently observed in patients that
      used statins prior to endarterectomy (468/595 [79%] with statin vs. 176/199 [88%]
      without statin; P=0.002). In multivariate analysis, age, coumarin-type
      anticoagulation use and statin use were independently correlated with carotid
      IPH. No association was observed between femoral IPH and clinical patient
      characteristics. CONCLUSION: Advanced age and coumarin-type anticoagulation use
      are associated with the occurrence of IPH, while statin use is associated with
      less IPH.

PMID- 21074772
TI  - Mixed-mode failure strength of implant-cement interface specimens with varying
      surface roughness.
AB  - Aseptic loosening at the implant-cement interface is a well-documented cause of
      failure in joint arthroplasty. Traditionally, the strength of the implant-cement
      interface is determined using uni-axial normal and shear loading tests. However,
      during functional loading, the implant fixation sites are loaded under more
      complex stress conditions. For this purpose, the strength of the implant-cement
      interface under mixed-mode tensile and shear loading conditions was determined in
      this study using interface specimens with varying interface roughness. For the
      lowest roughness value analyzed (R(a)=0.89 MUm), the interface strength was 0.40
      1.95 MPa at loading angles varying between pure tension and shear, whereas this
      was 4.90-9.90 MPa for the highest roughness value (R(a)=2.76 MUm). The interface
      strength during pure shear (1.95-9.90 MPa) was substantially higher than during
      pure tension (0.58-6.67 MPa). Polynomial regression was used to fit a second
      order interpolation function through the experimental interface strength data
      (R2=0.85; p<0.001), relating the interface strength (S [MPa]) to the interface
      loading angle (alpha [degrees]) and interface roughness (R(a) [MUm]):
      S(alpha,R(a))=0.891R2(a)+0.001alpha2-0.189R(a)-0.064alpha-0.060. Finally, an
      interface failure criterion was derived from the interface strength measurements,
      describing the risk of failure at the implant-cement interface when subjected to
      a certain tensile and shear stress using only the interface strength in pure
      tensile and shear direction. The findings presented in this paper can be used in
      numerical models to simulate loosening at the implant-cement interface.

PMID- 21074773
TI  - Characterization of muscle architecture in children and adults using magnetic
      resonance elastography and ultrasound techniques.
AB  - The purpose of this study is to characterize the muscle architecture of children
      and adults using magnetic resonance elastography and ultrasound techniques. Five
      children (8-12 yr) and seven adults (24-58 yr) underwent both tests on the vastus
      medialis muscle at relaxed and contracted (10% and 20% of MVC) states.
      Longitudinal ultrasonic images were performed in the same area as the phase image
      showing the shear wave's propagation. Two geometrical parameters were defined:
      the wave angle (alpha(_MRE)) corresponding to the shear wave propagation and the
      fascicule angle (alpha(_US)) tracking the path of fascicles. Moreover, shear
      modulus was measured at different localizations within the muscle and in the
      subcutaneous adipose tissue. The association of both techniques demonstrates that
      the shear wave propagation follows the muscle fascicles path, reflecting the
      internal muscle architecture. At rest, ultrasound images revealed waves
      propagating parallel to the children fascicle while adults showed oblique waves
      corresponding to already oriented (alpha(_US)=15.4+/-2.54 degrees ) muscle
      fascicles. In contraction, the waves' propagation were in an oblique direction
      for children (alpha(_US_10%MVC)=10.6+/-2.27 degrees , alpha(_US_20%MVC)=10.2+/
      2.29 degrees ) as well as adults (alpha(_US_10%MVC)=15.4+/-2.54 degrees ,
      alpha(_US_20%MVC)=17.2+/-2.44 degrees ). A stiffness variation (1 kPa) was found
      between the upper and lower parts of the adult VM muscle and a lower stiffness
      (1.85+/-0.17 kPa) was measured in the subcutaneous adipose tissue. This study
      demonstrates the feasibility of the MRE technique to provide geometrical insights
      from the children and adults muscles and to characterize different physiological
      media.

PMID- 21074775
TI  - A parallel pore and surface diffusion model for predicting the adsorption and
      elution profiles of lispro insulin and two impurities in gradient-elution
      reversed phase chromatography.
AB  - Lispro insulin (LPI), a widely used insulin analog, is produced on tons per year
      scale. Linear gradient reversed phase chromatography (RPC) is used in the
      production to separate LPI from two impurities, which differ from LPI by a single
      amino acid residue. A chromatography model for the ternary separation in this RPC
      process is unavailable from the literature. In this study, a parallel pore and
      surface diffusion model is developed and verified for LPI and the two impurities.
      The LPI can be recovered with high yield (>=95%) and high purity (>99.5%). A new
      method, which requires a small amount of materials and an order of magnitude
      fewer experiments, has been developed to estimate the solvent-modulated isotherm
      parameters. A modified reversed phase modulator model is developed to correlate
      the adsorption isotherms of LPI and impurities. A strategy has been developed for
      estimating the intrinsic pore diffusivity and surface diffusivity. Since the
      adsorption affinities decrease by more than three orders of magnitude as organic
      fraction (phi) increases from 0.19 to 0.40, the apparent diffusivities based on a
      pore diffusion model or a surface diffusion model can also vary by several orders
      of magnitude. For this reason, a pore diffusion model or a surface diffusion
      model with a constant apparent diffusivity cannot predict closely the
      chromatograms over the same range of organic fractions, concentrations, and
      loadings. The parallel pore and surface diffusion model with constant
      diffusivities can predict closely the frontal and elution profiles over a wide
      range of organic fractions (0.19-0.40), LPI concentrations (0.05-18 g/L), linear
      velocities (<10 cm/min), and loading volume (0.0004-13 CV). For large loading
      stepwise and linear gradient elution, the peaks of LPI and the impurities are
      strongly focused by self-sharpening and gradient focusing effects as a result of
      the steep decrease of adsorption affinity from the loading phi (0.19) to elution
      phi (>=0.27). When the ratio of diffusion rate to convection rate is greater than
      10, spreading due to diffusion is largely compensated by the focusing effects. As
      a result, a pore diffusion model with a constant pore diffusivity can predict
      closely the elution profiles in stepwise and linear gradient elution. The
      experimental yield values (>=95%) can be predicted to within +/-1% by the model.

PMID- 21074774
TI  - Microstructure and nanomechanical properties in osteons relate to tissue and
      animal age.
AB  - Material property changes in bone tissue with ageing are a crucial missing
      component in our ability to understand and predict age-related fracture. Cortical
      bone osteons contain a natural gradient in tissue age, providing an ideal
      location to examine these effects. This study utilized osteons from baboons aged
      0-32 years (n=12 females), representing the baboon lifespan, to examine effects
      of tissue and animal age on mechanical properties and composition of the
      material. Tissue mechanical properties (indentation modulus and hardness),
      composition (mineral-to-matrix ratio, carbonate substitution, and crystallinity),
      and aligned collagen content (aligned collagen peak height ratio) were sampled
      along three radial lines in three osteons per sample by nanoindentation, Raman
      spectroscopy, and second harmonic generation microscopy, respectively.
      Indentation modulus, hardness, mineral-to-matrix ratio, carbonate substitution,
      and aligned collagen peak height ratio followed biphasic relationships with
      animal age, increasing sharply during rapid growth before leveling off at sexual
      maturity. Mineral-to-matrix ratio and carbonate substitution increased 12% and
      6.7%, respectively, per year across young animals during growth, corresponding
      with a nearly 7% increase in stiffness and hardness. Carbonate substitution and
      aligned collagen peak height ratio both increased with tissue age, increasing 6
      12% across the osteon radii. Indentation modulus most strongly correlated with
      mineral-to-matrix ratio, which explained 78% of the variation in indentation
      modulus. Overall, the measured compositional and mechanical parameters were the
      lowest in tissue of the youngest animals. These results demonstrate that
      composition and mechanical function are closely related and influenced by tissue
      and animal age.

PMID- 21074776
TI  - Growth of Ag-nanoparticles using aspartic acid in aqueous solutions.
AB  - Spectrophotometric, kinetic, and transmission electron microscopic (TEM) data for
      the formation of Ag-nanoparticles using aspartic acid (Asp) as reductant are
      reported for the first time. In the formation of transparent silver sols, an
      alkaline medium is required. The silver nanoparticles are spherical, uniform
      particle size, and strongly depend on the [Asp]. The apparent rate constant
      decreases with [Asp] (from 4.0 to 24.0*10(-4)moldm(-3), the rate constants
      decreased from 2.6*10(-4) to 0.3*10(-4)s(-1)). For a certain reaction time, i.e.,
      30min, the absorbance of the silver sol first increased until it reached a
      maximum, and then decreased with [Asp]. Kinetic and TEM results indicate that the
      size of the Ag-nanoparticles depends on the [Asp]. It is proposed that the
      oxidation of Asp occurs by the adsorbed Ag(+) ions on the surface of Ag(2)O
      particles.

PMID- 21074777
TI  - Serum proteome analysis for profiling protein markers associated with lymph node
      metastasis in colorectal carcinoma.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer death in the human
      population worldwide. In China, CRC ranks fifth among cancer deaths, with a
      continuous increase in the incidence. Most CRC patients have lymph node
      metastasis (LNM) when first diagnosed. Two-dimensional (2D) serum proteome
      analysis may be useful in discovering new biomarkers that may aid in the
      diagnosis and therapy of CRC patients. To determine the tumour metastasis
      specific antigen markers of CRC metastasis, sera from 32 patients with non-LNM
      CRC and 40 patients with LNM CRC were selected for screening using 2D serum
      proteome analysis combined with mass spectrometry (MS). Pretreatment strategies,
      including sonication and depletion of albumin and immunoglobulin (Ig) G, were
      adopted for screening differentially expressed proteins of low abundance in
      serum. By 2D image analysis and Matrix-assisted laser desorption/ionisation-time
      of flight (MALDI-TOF)-MS identification, eight protein spots were differentially
      expressed and successfully identified. The molecule transthyretin (TTR) was
      further studied in these sera by enzyme-linked immunosorbent assay. TTR appears
      to be a potential CRC metastasis-specific serum biomarker, which may be of value
      in the clinical detection and management of CRC.

PMID- 21074779
TI  - Unpaired extinction: implications for treating post-traumatic stress disorder.
AB  - Extinction of fear is important for treating stress-related conditions
      particularly post-traumatic stress disorder (PTSD). Although traditional
      extinction presents the feared stimulus by itself, there is evidence from both
      clinical and basic research that repeatedly presenting the feared stimulus by
      itself does not prevent fear from returning. This renewal or relapse can be
      "thwarted" by unpaired extinction-presentations of the feared stimulus and the
      event producing the fear. However, no matter how effective standard unpaired
      extinction may be in the laboratory, repeated presentation of a traumatic event
      is untenable. To make an unpaired extinction procedure more clinically relevant,
      we classically conditioned the rabbit nictitating membrane response using
      electrical stimulation or air puff as the unconditioned stimulus and then during
      unpaired extinction reduced both the intensity of the unconditioned stimulus and
      the days of unpaired stimulus presentations. We found unpaired extinction reduced
      conditioned and exaggerated unconditioned responding (an animal analog of PTSD
      called conditioning-specific reflex modification) and could be accomplished with
      a weak unconditioned stimulus as long as extended presentations were used.
      Surprisingly, brief presentations of a weak unconditioned stimulus or extended
      presentations of a strong one made the exaggerated responses stronger. One
      implication is that brief treatment may not just be ineffectual; it may heighten
      the symptoms of PTSD. Another implication is that using strong stimuli may also
      heighten those symptoms.

PMID- 21074781
TI  - "Who's my doctor?".

PMID- 21074780
TI  - A novel liposome-based therapy to reduce complement-mediated injury in
      revascularized tissues.
AB  - BACKGROUND: Ischemia/reperfusion (IR) injury is an unavoidable consequence of
      tissue transplantation or replantation that often leads to inflammation and cell
      death. Excessive complement activation following IR induces endothelial cell
      injury, altering vascular and endothelial barrier function causing tissue
      dysfunction. To mitigate the IR response, various systemic anti-complement
      therapies have been tried. Recently, we developed a localized therapy that uses
      biotinylated fusogenic lipid vesicles (BioFLVs) to first incorporate biotin
      tethers onto cell membranes, which are then used to bind therapeutic fusion
      proteins containing streptavidin (SA) resulting in the decoration of cell
      membranes. The therapy is applied in two steps using solutions delivered intra
      arterially. MATERIALS AND METHODS: Alteration of formulation, concentration and
      duration of incubation of BioFLVs were conducted to demonstrate the ability of
      the system to modulate biotin tether incorporation in cultured cells. Using a rat
      hind limb model, the ability of BioFLVs to decorate endothelium of femoral
      vessels with FITC-labeled SA for 48 h of reperfusion was demonstrated. The
      feasibility of a BioFLV-based anti-complement therapy was tested in cultured
      cells using SA fused with vaccinia virus complement control protein (SA-VCP), a
      C3 convertase inhibitor. Human ovarian carcinoma (SKOV-3) cells were incubated
      with BioFLVs first and then with SA-VCP. To activate complement the cells were
      treated with a SKOV-3-specific antibody (trastuzumab) and incubated in human
      serum. RESULTS: Decoration of cells with SA-VCP effectively reduced complement
      deposition. CONCLUSIONS: We conclude that BioFLV-mediated decoration of cell
      membranes with anti-complement proteins reduces complement activation and
      deposition in vitro and has the potential for application against
      inappropropriate complement activation in vivo.

PMID- 21074782
TI  - Effects of platelet-rich plasma on intestinal anastomotic healing in rats: PRP
      concentration is a key factor.
AB  - BACKGROUND: Few studies have examined the effects of platelet-rich plasma (PRP)
      on intestinal anastomotic healing. The applied preparation methods and PRP
      concentrations used in the few studies that have been carried out varied
      markedly. Therefore, the positive effects of PRP on the anastomotic healing
      process remain unclear. The aim of this study is to examine the effects of
      different concentrations of PRP on intestinal anastomotic healing. MATERIAL AND
      METHODS: From SD rat blood, three different concentrations of plasma were
      prepared: high-concentrated PRP (H-PRP: platelet count 5 * 10(6)/mm(3)), low
      concentrated PRP (L-PRP: 2 * 10(6)/mm(3)), and platelet-poor plasma (PPP). Male
      SD rats underwent proximal jejunal anastomosis and central venous
      catheterization. Rats were divided into four groups (n = 12 for each group):
      control, PPP, L-PRP, and H-PRP groups. Two types of PRP and PPP (0.21 mL) were
      applied to each anastomosis line, with the exception of the control group. Total
      parenteral nutrition (TPN) solutions were administered (151 kcal/kg/d). Five days
      after surgery, anastomotic bursting pressure (ABP) in situ and hydroxyproline
      concentration (HYP) in anastomotic tissue were evaluated. RESULTS: The ABP values
      of control, PPP, L-PRP, and H-PRP groups were 171 +/- 20, 174 +/- 23, 189 +/- 17,
      and 148 +/- 25 mmHg, respectively. The HYP values of each group were 516 +/- 130,
      495 +/- 123, 629 +/- 120, and 407 +/- 143 MUg/g dry tissue. Compared with the
      other groups, the L-PRP group exhibited a significant increase in both ABP and
      HYP, while the H-PRP group exhibited a significant decrease in these two
      variables. As a result, L-PRP was considered to promote anastomotic wound
      healing, but H-PRP was considered to inhibit it. There was no significant
      difference between the PPP group and the control group. CONCLUSIONS: PRP
      concentration plays a crucial role in the efficacy of PRP. PRP might exert
      positive effects on intestinal anastomotic healing in a dose-dependent manner up
      to a certain level, but adverse effects occur when it is highly concentrated. The
      essential PRP action appears to be driven by the platelets themselves.

PMID- 21074783
TI  - Glycyrrhizin treatment is associated with attenuation of lipopolysaccharide
      induced acute lung injury by inhibiting cyclooxygenase-2 and inducible nitric
      oxide synthase expression.
AB  - Glycyrrhizin (GL), a major active constituent of licorice root, has been
      attributed numerous pharmacologic effects, including anti-inflammatory, anti
      viral, anti-tumor, and hepatoprotective activities. In this study, we
      investigated the anti-inflammatory effect of GL on lipopolysaccharide (LPS)
      induced acute lung injury (ALI) in mice. ALI was induced in Balb/c mice by
      intratracheal instillation of LPS (1 mg/kg). Before 1 h of LPS administration,
      the mice received intraperitoneal injection of GL at varied doses (10, 25, and 50
      mg/kg). The severity of pulmonary injury was evaluated 12 h after LPS
      administration. GL pretreatment led to significant attenuation of LPS induced
      evident lung histopathologic changes, alveolar hemorrhage, and neutrophil
      infiltration with evidence of reduced myeloperoxidase (MPO) activity. The lung
      wet/dry weight ratios, as an index of lung edema, were markedly reduced by GL
      pretreatment. The concentrations of pro-inflammatory cytokines interleukin (IL)
      1beta and tumor necrosis factor (TNF)-alpha were elevated in bronchoalveolar
      lavage fluid (BALF) after LPS administration, which were significantly inhibited
      by GL pretreatment. GL pretreatment also reduced the concentrations of nitric
      oxide (NO) in lung tissues. Furthermore, the expression of cyclooxygenase-2 (COX
      2) and inducible nitric oxide synthase (iNOS) was suppressed by GL pretreatment.
      In conclusion, GL potently protected against LPS-induced ALI, and the protective
      effects of GL may attribute partly to the suppression of COX-2 and iNOS
      expression.

PMID- 21074784
TI  - In vivo characterization of Hyalonect, a novel biodegradable surgical mesh.
AB  - BACKGROUND: Musculoskeletal reconstructive surgery often requires removal of
      significant quantities of bone tissue, such as the periosteum, causing critical
      problems following surgery like friction between different tissues and adhesion
      of soft tissues to the underlying bone. We studied the long-term host response
      and closure of large bone defects for periosteal reconstruction using Hyalonect,
      a novel membrane comprising knitted fibers of esterified hyaluronan, (HYAFF11).
      MATERIALS AND METHODS: For biological characterization, 162 rats were used in a
      defect model in which a section of the dorsal muscular fascia was removed, and
      the membrane behavior observed over 540 d using conventional histology, with sham
      operated rats as controls. In addition, Hyalonect was used to cover defects made
      in the humeri of 7 dogs, filled with a variety of conventional bone filling
      compounds, and the regeneration process observed after 6 wks using histology.
      RESULTS: Low levels of inflammation were observed in the dorsal muscle fascia
      defect model, with cellular colonization of the mesh by 30 d, vascularization by
      120 days, matrix fiber organization by 270 d, and the appearance of connective
      tissue identical to the surrounding tissue between 365 and 540 d, without the
      formation of fibrotic tissue. In addition, Hyalonect was shown to allow the
      regeneration of bone within the humeral defects whilst preventing fibrotic tissue
      in-growth, and allowing regeneration of tissue which, by 6 wk, had begun to
      resemble natural periosteal tissue. CONCLUSION: Hyalonect is suitable for
      improving the outcome of the final phases of orthopedic and trauma reconstructive
      surgical procedures, especially in the reconstruction of periosteal tissue.

PMID- 21074785
TI  - Erythropoietin as additive of HTK preservation solution in cold
      ischemia/reperfusion injury of steatotic livers.
AB  - BACKGROUND: Organ shortage in liver transplantation has justified usage of
      marginal donor livers to expand the donor organ pool. The particular
      susceptibility of steatotic livers to I/R injury necessitates optimal
      preservation conditions in order to minimize preservation-reperfusion injury for
      successful transplantation. METHODS: The effect of erythropoietin (EPO) as
      additive to HTK preservation solution was studied in a mouse model. Lean and
      steatotic livers were harvested, stored for 24 h in 4 degrees C HTK solution
      containing either EPO or saline and reperfused for 2 h with 37 degrees C Krebs
      Henseleit buffer. Livers without cold storage served as sham controls. RESULTS:
      Flushing of livers upon cold storage revealed a transaminase release, which was 2
      to 10-fold higher in steatotic versus lean livers. EPO was effective in reducing
      the enzyme release to 50% in steatotic but not in lean livers. EPO prevented cold
      storage-induced denudation of the endothelial lining in steatotic livers, but
      aggravated it in lean livers. During reperfusion, steatotic livers presented with
      lower oxygen consumption and higher enzyme release than lean livers. In all
      livers, parameters of reperfusion injury remained unaffected by EPO. Expression
      of UCP2 was found markedly higher in steatotic livers. After I/R, steatotic
      livers revealed a significant drop of UCP2, whereas expression in lean livers was
      only slightly affected. EPO diminished Erk phosphorylation to almost the same
      extent in both mouse strains. CONCLUSION: Fortification of the preservation
      solution by EPO ameliorates cold ischemic injury of steatotic livers and may thus
      be considered for use as an adjunctive agent to increase the success of
      transplanting steatotic livers.

PMID- 21074786
TI  - Changes in core temperature during peritoneal insufflation: comparison of two CO2
      humidification devices in pigs.
AB  - BACKGROUND: Various modifications of the physical status of CO2 have been used to
      reduce hypothermia caused by flow of insufflating gas. This animal study aimed to
      investigate the effects on core temperature, of insufflation with CO2 using two
      different humidification devices: unheated, humidified CO2 using the Modified
      Aeroneb system (Nektar, San Carlos, CA) and warmed, humidified CO2 using the HME
      Booster (Medisize, Hillegom, The Netherlands). METHODS: We undertook a
      prospective four-session study on a homogeneous group of four pigs. After general
      anesthesia, all animals were treated successively with the following protocols in
      a randomized order at 8-d intervals: Control (no pneumoperitoneum), Standard
      (unheated, unhumidified CO2), Modified-Aeroneb (unheated, humidified CO2 by cold
      nebulization), HME-Booster (heated, humidified CO2). The core temperature of the
      animals was recorded every 10 min. RESULTS: The temperature decrease is
      significantly influenced by time (P=0.0001; ANOVA), by the insufflation method
      (P=0.01), and by the interaction between time and the insufflation method
      (P=0.0001). The method of contrasts showed the following results:--The
      temperature decrease in the Standard group and HME-Booster group became greater
      than in the Control group after 40 min (P=0.02)--The temperature decrease in the
      Modified-Aeroneb group became greater than in the Control group after 100 min
      (P=0.04)--The temperature decrease in the Modified-Aeroneb group was less than in
      the HME-Booster group after 40 min (P=0.04) and less than in the Standard group
      after 60 min (P=0.01)--The temperature decrease in the Standard group was greater
      than in the HME-Booster group after 160 min (P=0.005). CONCLUSIONS: Compared with
      the HME-Booster system, the Modified-Aeroneb is at least as effective in limiting
      the drop in core temperature during laparoscopic insufflation.

PMID- 21074787
TI  - Is gender related to the stage of colorectal cancer at initial presentation in
      young patients?
AB  - BACKGROUND: The incidence of colorectal cancer (CRC) in young adults is rising,
      and young age is a predictor of poor survival. The purpose of this study was to
      examine factors leading to increased mortality in patients <= 50 years of age,
      and to examine this population for characteristics that could lead to benefit
      from CRC screening. METHODS: Charts of patients 50 years of age and under,
      diagnosed with CRC from 1998 through 2007, at our community teaching hospital,
      were reviewed retrospectively. Demographics, social and family history, staging,
      treatment and death were evaluated. Mann Whitney, Fisher Exact, and chi(2) tests
      were used with P <0.05 considered statistically significant. RESULTS: Forty-five
      young patients with CRC were identified. Twenty-five patients were female and 20
      male; the mean age was 43.6 y. Most patients presented with rectal bleeding.
      Right-sided cancers had a higher presenting stage (P < 0.05). Men had both a
      higher presenting stage (P = 0.35) and a higher incidence of smoking compared
      with women (P = 0.001). Female patients were more likely to have left-sided CRC
      (65%) compared with men (35%). Ninety-six percent of patients underwent surgical
      resection; 14 patients died. CONCLUSIONS: CRC in young adults is not common, but
      is often advanced when discovered. Diagnostic efforts should be aggressive in
      young patients who have rectal bleeding, especially young male smokers.
      Sigmoidoscopy is not adequate for comprehensive diagnosis of CRC in young
      patients, as the majority have right-sided colon cancers, which often result in
      subsequent presentation of the disease at a higher stage, risk, and mortality
      rate.

PMID- 21074788
TI  - Complications in immunosuppressive therapy of liver transplant recipients.
AB  - BACKGROUND: In liver transplantation (LT), modern immunosuppressive protocol is
      focused on early corticosteroid (CS) weaning. The aim of the study was to
      investigate all early transplant-related complications using Clavien grading
      system, in order to identify a significant relation in two homogenous groups of
      consecutive liver transplanted patients, only different for steroid avoidance in
      immunosuppressive regimen. MATERIALS AND METHODS: One group was treated with a
      tacrolimus-based CS-free immunosuppressive protocol, the other one underwent
      tacrolimus plus low dose CS therapy. The preoperative continuous variables
      analyzed were age, gender, model for end-stage liver disease (MELD) score, and
      the pre-allocation score for predicting survival following liver transplantation
      (P-SOFT). RESULTS: There were 39 patients in Group A (CS free) (37.9%), and 64
      patients in Group B (CS on board) (62.1%). No statistically significant
      differences between the two groups were detected regarding the incidence and
      Clavien grade of complications (P = 0.116). No significant relation was revealed
      between Clavien rate of complications and tacrolimus-based CS-free
      immunosuppressive protocol, comparing the two subgroup of patient with P-SOFT
      score < 6 and >= 6 (P = 0.193). This association was noted comparing the two
      subgroups on tacrolimus plus low dose CS regimen (P = 0.013). CONCLUSION: In this
      series, the use of CS in sick patient is associated with higher morbidity
      identified by the Clavien classification.

PMID- 21074789
TI  - Leukocyte depletion, ischemic injury, and organ preservation.

PMID- 21074790
TI  - Low dose oral desmopressin for nocturnal polyuria in patients with benign
      prostatic hyperplasia: a double-blind, placebo controlled, randomized study.
AB  - PURPOSE: We evaluated the long-term efficacy and safety of low dose oral
      desmopressin in elderly patients with benign prostatic hyperplasia with more than
      nocturnal voids and nocturnal polyuria more than 30% of total daily urine volume.
      MATERIALS AND METHODS: Eligible patients with benign prostatic hyperplasia older
      than 65 years with nocturia, nocturnal polyuria and International Prostate
      Symptom Score 14 or greater were included in the study. All patients received
      placebo or 0.1 mg desmopressin orally at bedtime. Patients were required to visit
      the outpatient clinic from the first visit, and after 1, 3, 6 and 12 months of
      treatment. Patients maintained flow volume charts and used diaries to record
      voiding data throughout the study. During followup urinalysis, urine sodium,
      urine osmolality, serum electrolytes, prostate specific antigen, International
      Prostate Symptom Score, quality of life, transrectal ultrasonography of prostate,
      uroflowmetry and post-void residual urine volume were performed at each visit.
      RESULTS: A total of 115 patients were enrolled in the study and randomized as 58
      in the placebo group and 57 in the desmopressin group. Desmopressin significantly
      decreased nocturnal urine output and the number of nocturia episodes, and
      prolonged the first sleep period (p < 0.01). Compared to before treatment
      desmopressin gradually decreased serum sodium and induced statistically but not
      clinically significant hyponatremia after 12 months of treatment. No serious
      systemic complications were found during medication. CONCLUSIONS: Low dose oral
      desmopressin is an effective and well tolerated treatment for nocturnal polyuria
      in the lower urinary tract symptoms of patients with benign prostatic
      hyperplasia. Long-term desmopressin therapy gradually decreases serum sodium and
      it might induce hyponatremia even in patients without initial hyponatremia. For
      long-term desmopressin administration serum sodium should be assessed carefully,
      at least at 1 week after treatment.

PMID- 21074791
TI  - Complications of stone baskets: 14-year review of the manufacturer and user
      facility device experience database.
AB  - PURPOSE: We categorized trends in failure of the stone baskets as reported in the
      United States Food and Drug Administration Manufacturer and User Facility Device
      Experience database. MATERIALS AND METHODS: We queried the online database using
      the code for stone baskets (FFL) from January 1996 to December 2009. Variables
      extracted were the type of basket, malfunction and treatment, and patient
      outcome. RESULTS: We identified 556 adverse events related to stone baskets. The
      device configuration was tipped in 48% of cases, tipless in 36%, forceps in 8%
      and the Stone ConeTM in 8%. Malfunction type included detachment of a portion of
      the basket in 49% of cases, breakage without detachment in 39% and inability to
      withdraw the basket in 12%. Compared to the early period studied (1996 to 2004)
      there was a 3-fold increase in adverse events from 2005 to 2007 and a 6-fold
      increase from 2008 to 2009. Of adverse events 79% and 11% were managed by
      endoscopy and open surgery, respectively. Of the patients 42 experienced serious
      complications requiring major surgery, including ureteral reconstruction in 7,
      reimplantation in 4 and nephrectomy in 7. CONCLUSIONS: With the increased use of
      stone baskets in the upper collecting system the number of adverse events has
      increased. Urologists should remain vigilant to prevent, recognize and manage
      these events.

PMID- 21074792
TI  - Microsurgical spermatocelectomy: technique and outcomes of a novel surgical
      approach.
AB  - PURPOSE: A microsurgical approach to spermatocelectomy theoretically minimizes
      the risk of injury to the epididymis and testicular blood supply. We present the
      technique of microsurgical spermatocelectomy and report our perioperative and
      recurrence outcomes. MATERIALS AND METHODS: In a 15-year period 23 men with a
      total of 36 epididymal cystic masses underwent microsurgical resection with
      confirmation of spermatocele diagnosis by intraoperative identification of sperm
      in the cyst fluid. We reviewed pathology reports for resected epididymal tissue
      in the spermatocele specimen. Postoperative outcome measures included
      complications, sperm count changes, improvement in pain and fertility, and cyst
      recurrence. RESULTS: Mean spermatocele size was 5.0 cm (range 1 to 15). Common
      indications for surgery included pain in 35% of cases, infertility in 30% and the
      2 conditions in 13%. A total of 13 patients (57%) underwent simultaneous
      procedures for concomitant varicocele and/or hydrocele with a mean overall
      surgical time of 152 minutes. A single scrotal hematoma managed conservatively
      was the only postoperative complication. There was no case of infection.
      Avoidance of inadvertent epididymal resection was shown by absent epididymal
      tissue in each of the 36 spermatocele pathology specimens. Also, no patient with
      preoperative and postoperative semen analyses available experienced a decreased
      sperm count, confirming the avoidance of iatrogenic epididymal tubule
      obstruction. At a mean followup of 17.3 months no man had cyst recurrence or
      testicular atrophy and all with preoperative pain reported improvement. One
      patient with preoperative infertility achieved pregnancy 12 months after surgery.
      CONCLUSIONS: Microsurgical spermatocelectomy is safe and effective with a minimal
      risk of epididymal injury, testicular atrophy and recurrence.

PMID- 21074793
TI  - Same session bilateral ureteroscopy is safe and efficacious.
AB  - PURPOSE: Bilateral ureteroscopy can be done in 1 sitting, obviating the need for
      multiple procedures. We analyzed our experience with same session bilateral
      ureteroscopy to determine its safety and efficacy. MATERIALS AND METHODS: In this
      retrospective study of a 9-year period at Emory University Hospital 1,575
      consecutive ureteroscopic procedures were done, of which 95 (6.0%) were done as
      same session bilateral ureteroscopy, thus constituting our study cohort.
      Bilateral procedures were performed for urolithiasis in 71 cases, urothelial
      carcinoma in 9, ureteral stricture in 2 and another indication in 13. Patients
      were followed at least 1 month postoperatively to evaluate procedural success and
      assess perioperative complications. RESULTS: Mean age of the 44 male and 40
      female patients was 49.8 years. Multiple procedures were done in 9 patients and
      same session bilateral ureteroscopy was done in 93 of 95 (98%). Intraoperative
      and postoperative (greater than 1 month) bilateral stone-free rates were 86% and
      64%, respectively. The mean change in serum creatinine postoperatively was 0.02
      mg/dl (range -0.9 to 1.3). No patient had acute postoperative azotemia.
      Postoperative complications in 9.7% of patients included pain necessitating an
      emergency room visit in 4, pyelonephritis/urinary tract infection in 2, and
      urinary retention, intractable stent pain leading to early removal and
      urosepsis/death in 1 each. CONCLUSIONS: Same session bilateral ureteroscopy is
      efficacious and safe to evaluate and treat upper tract pathology. While most
      complications are minor, they may be higher than that typically reported for
      unilateral ureteroscopic procedures.

PMID- 21074794
TI  - Shock wave lithotripsy is not predictive of hypertension among community stone
      formers at long-term followup.
AB  - PURPOSE: Concern exists over the subsequent development of hypertension after
      shock wave lithotripsy for the treatment of symptomatic urolithiasis. Referral
      bias and lack of long-term followup have been limitations of prior studies.
      MATERIALS AND METHODS: We identified all Olmsted County, Minnesota residents with
      a diagnosis of urolithiasis from 1985 to 2008. The charts were electronically
      queried for hypertension and obesity by diagnostic codes, and use of shock wave
      lithotripsy by surgical codes. All patients first diagnosed with hypertension
      before or up to 90 days after the first documented kidney stone were considered
      to have prevalent hypertension and were excluded from analysis. Cox proportional
      hazards models were used to assess the association of shock wave lithotripsy with
      a subsequent diagnosis of hypertension. RESULTS: We identified 6,077 patients
      with incident urolithiasis with more than 90 days of followup. We excluded 1,295
      (21.3%) members of the population for prevalent hypertension leaving 4,782
      patients with incident urolithiasis for analysis. During an average followup of
      8.7 years new onset hypertension was diagnosed in 983 (20.6%) members of the
      cohort at a mean of 6.0 years from the index stone date. Only 400 (8.4%) patients
      in the cohort were treated with shock wave lithotripsy. There was no significant
      association between shock wave lithotripsy and the development of hypertension in
      univariate (p = 0.33) and multivariate modeling controlling for age, gender and
      obesity (HR 1.03; 95% CI 0.84, 1.27; p = 0.77). CONCLUSIONS: In a large
      population based cohort of kidney stone formers we failed to identify an
      association between shock wave lithotripsy and the subsequent long-term risk of
      hypertension.

PMID- 21074795
TI  - Predictors of outcome for blunt high grade renal injury treated with conservative
      intent.
AB  - PURPOSE: Management for blunt high grade renal injury is controversial with most
      disagreement concerning indications for exploration. At our institution all
      patients are considered candidates for conservative treatment regardless of
      injury grade or computerized tomography appearance with clinical status the sole
      determinant for intervention. We define clinical factors predicting the need for
      emergency intervention as well the development of complications. MATERIALS AND
      METHODS: We analyzed the records of 117 patients with high grade renal injury
      (III to V) secondary to blunt trauma who presented to our institution in an 8
      year period. Patients were categorized by the need for emergency intervention
      and, in those treated conservatively, by complications. We generated logistic
      regression models to identify significant clinical predictors of each outcome.
      RESULTS: Grade III to V injury occurred in 48 (41.1%), 42 (35.9%) and 27 patients
      (23%), respectively. Of the 117 patients 20 (17.1%) required emergency
      intervention. On multivariate analysis only grade V injury (RR 4.4, 95% CI 1.9
      10.5, p = 0.001) and the need for platelet transfusion (RR 8.9, 95% CI 2.1-32.1,
      p < 0.001) significantly predicted the need for intervention. A total of 90
      patients (82.9%) who did not require emergency intervention underwent a trial of
      conservative treatment, of whom 9 (9.3%) experienced complications requiring
      procedural intervention. On multivariate analysis only patient age (RR 1.06, 95%
      CI 1.02-1.1, p = 0.004) and hypotension (RR 12, 95% CI 1.9-76.7, p = 0.009) were
      significant predictors. CONCLUSIONS: High grade injury can be successfully
      managed conservatively. However, grade V injury and the need for platelet
      transfusion predict the need for emergency intervention while older patient age
      and hypotension predict complications.

PMID- 21074796
TI  - Management for prostate cancer treatment related posterior urethral and bladder
      neck stenosis with stents.
AB  - PURPOSE: Prostate cancer treatment has the potential to lead to posterior
      urethral stricture. These strictures are sometimes recalcitrant to dilation and
      urethrotomy alone. We present our experience with the Urolume(r) stent for
      prostate cancer treatment related stricture. MATERIALS AND METHODS: A total of 38
      men with posterior urethral stricture secondary to prostate cancer treatment were
      treated with Urolume stenting. Stents were placed in all men after aggressive
      urethrotomy over the entire stricture. A successfully managed stricture was
      defined as open and stable for greater than 6 months after any necessary
      secondary procedures. RESULTS: The initial success rate was 47%. After a total of
      31 secondary procedures in 19 men, including additional stent placement in 8
      (18%), the final success rate was 89% at a mean +/- SD followup of 2.3 +/- 2.5
      years. Four cases (11%) in which treatment failed ultimately requiring urinary
      diversion (3) or salvage prostatectomy (1). Incontinence was noted in 30 men
      (82%), of whom 19 (63%) received an artificial urinary sphincter a mean of 7.2 +/
      2.4 months after the stent. Subanalysis revealed that irradiated men had longer
      strictures (3.6 vs 2.0 cm, p = 0.003) and a higher post-stent incontinence rate
      (96% vs 50%, p < 0.001) than men who underwent prostatectomy alone but the
      initial failure rate was similar (54% vs 50%, p = 0.4). CONCLUSIONS: Urolume
      stenting is a reasonable option for severe post-prostate cancer treatment
      stricture when patients are unwilling or unable to undergo open reconstructive
      surgery. Incontinence should be expected. The need for additional procedures is
      common and in some men may be required periodically for the lifetime of the
      stent.

PMID- 21074797
TI  - Glanuloplasty with urethral flap after partial penectomy.
AB  - PURPOSE: We describe a surgical technique to reconstruct the glans secondary to
      partial penectomy or traumatic partial amputation as well as its complications.
      We assessed urethral flap vitality and the tumor recurrence rate using this
      technique. MATERIALS AND METHODS: Glanuloplasty with a urethral flap was done in
      10 patients who underwent partial penectomy for penile squamous cell carcinoma.
      We reconstructed the neoglans with a urethral flap at the same surgical
      resection. Mean patient age was 61 years (range 18 to 71). Mean followup was 11
      months (range 5 to 17). RESULTS: We noted no neomeatal stenosis or flap necrosis
      secondary to the technique. The early tumor recurrence rate was 10% and the
      penile curvature rate was 10%. Penile curvature was ventral with no associated
      penetration difficulty. CONCLUSIONS: This simple, reproducible technique has
      satisfactory functional and cosmetic results, and an acceptable complication rate
      for this type of pathological condition.

PMID- 21074798
TI  - Multi-institutional assessment of ureteroscopic laser papillotomy for chronic
      flank pain associated with papillary calcifications.
AB  - PURPOSE: We evaluated the long-term safety, efficacy and durability of
      ureteroscopic laser papillotomy for chronic flank pain associated with renal
      papillary calcifications. MATERIALS AND METHODS: We reviewed the medical records
      of all patients who underwent ureteroscopic laser papillotomy in the absence of
      free urinary calculi at our institutions from 1998 through 2008. Success was
      defined as patient report of significant pain relief. The duration of response
      was considered the time from papillotomy to repeat papillotomy in the same renal
      unit, patient report of recurrent pain or final followup. RESULTS: Ureteroscopic
      Ho:YAG laser papillotomy was done a total of 176 times in 65 patients, including
      147 unilateral and 29 bilateral procedures. Of the patients 39 underwent multiple
      procedures (2 to 12). Symptomatic followup was available in 50 patients (146
      procedures) during a mean of 38 months. Significantly less pain was reported
      after 121 procedures (83%). The mean duration of response per procedure was 26
      months and 30 patients (60%) had a mean remission duration of greater than 1
      year. Postoperatively hospital admission was required after 14 procedures (8%).
      There was no significant change in the mean estimated glomerular filtration rate
      during a mean 41.3-month followup. Seven of the 65 patients (11%) had
      hypertension before papillotomy. In 3 of the 49 patients (6.1%) with adequate
      followup new hypertension developed during a mean of 38 months. CONCLUSIONS:
      Ureteroscopic laser papillotomy is safe and effective. In patients with papillary
      calcifications and characteristic chronic, noncolicky pain this procedure
      provides significant, moderately durable symptom relief.

PMID- 21074799
TI  - Robot assisted extended pelvic lymphadenectomy at radical cystectomy: lymph node
      yield compared with second look open dissection.
AB  - PURPOSE: Robot assisted radical cystectomy outcomes show feasibility and
      potential benefits for patient recovery. However, it is difficult to judge the
      completeness of extended robot assisted vs open pelvic lymph node dissection
      using only the lymph node count and template description. We performed a
      prospective protocol in which radical cystectomy and pelvic lymph node dissection
      done in robot assisted fashion were followed by second look open pelvic lymph
      node dissection. Our primary objective was to determine the fraction of lymph
      nodes yielded by robot assisted pelvic lymph node dissection. MATERIALS AND
      METHODS: Patients with pure transitional cell carcinoma and no locally advanced
      features were selected for robot assisted radical cystectomy. A team of 2
      urological oncologists performed radical cystectomy and pelvic lymph node
      dissection in robot assisted fashion, followed by second look open pelvic lymph
      node dissection. Lymph nodes from robot assisted dissection were submitted in up
      to 8 separate specimens by anatomical location. Any additional specimens
      retrieved at open dissection were submitted separately. RESULTS: The protocol was
      completed in 11 patients from October 2007 to June 2009. The median yield of
      robot assisted and second look open pelvic lymph node dissection was 43 (range 19
      to 63) and 4 (range 0 to 8), respectively, for an overall robot assisted yield of
      93%. Of second look open pelvic lymph node dissections 67% were clear of residual
      tissue, 13% had tissue without lymph nodes and 20% had 1 or more lymph nodes.
      Median operative time for robot assisted pelvic lymph node dissection was 117
      minutes. Concurrently open radical cystectomy without required multiple lymph
      node specimen submission yielded a median 24 nodes. CONCLUSIONS: Our data showing
      a robot assisted pelvic lymph node dissection yield of 93% of that of open
      surgery should allay concern that the robot assisted technique limits the
      completeness of pelvic lymph node dissection.

PMID- 21074800
TI  - Editorial comment.

PMID- 21074801
TI  - Editorial comment.

PMID- 21074802
TI  - Effect of preoperative nutritional deficiency on mortality after radical
      cystectomy for bladder cancer.
AB  - PURPOSE: Poor preoperative nutritional status is a risk factor for adverse
      outcomes after major surgery. We evaluated the effect of preoperative nutritional
      deficiency on perioperative mortality and overall survival in patients undergoing
      radical cystectomy for bladder cancer. MATERIALS AND METHODS: A total of 538
      patients underwent radical cystectomy for urothelial carcinoma between January
      2000 and June 2008, and had nutritional parameters documented. Patients with
      preoperative albumin less than 3.5 gm/dl, body mass index less than 18.5 kg/m(2)
      or preoperative weight loss greater than 5% of body weight were considered to
      have nutritional deficiency. Primary outcomes were 90-day mortality and overall
      survival. Survival was estimated using Kaplan-Meier analysis and compared using
      the log rank test. Cox proportional hazards models were used for multivariate
      survival analysis. RESULTS: Of 538 patients 103 (19%) met the criteria for
      nutritional deficiency. The 90-day mortality rate was 7.3% overall (39 deaths),
      with 16.5% in patients with nutritional deficiency and 5.1% in the others (p <
      0.01). Nutritional deficiency was a strong predictor of death within 90 days on
      multivariate analysis (HR 2.91; 95% CI 1.36, 6.23; p < 0.01). Overall survival at
      3 years was 44.5% (33.5, 54.9) for nutritionally deficient patients and 67.6%
      (62.4, 72.2) for those who were nutritionally normal (p < 0.01). On multivariate
      analysis nutritional deficiency cases had a significantly higher risk of all
      cause mortality (HR 1.82; 95% CI 1.25, 2.65; p < 0.01). CONCLUSIONS: Nutritional
      deficiency, as measured by preoperative weight loss, body mass index and serum
      albumin, is a strong predictor of 90-day mortality and poor overall survival.
      Prospective studies are needed to demonstrate the best indices of preoperative
      nutritional status and whether nutritional intervention can alter the poor
      prognosis for patients treated with radical cystectomy who have nutritional
      deficiencies.

PMID- 21074803
TI  - Onset of efficacy of tadalafil once daily in men with erectile dysfunction: a
      randomized, double-blind, placebo controlled trial.
AB  - PURPOSE: We evaluated the efficacy onset and safety of tadalafil 2.5 and 5 mg
      once daily for 14 days compared with placebo in men with erectile dysfunction.
      MATERIALS AND METHODS: In this randomized, double-blind, placebo controlled,
      parallel group study we randomized 372 men after a 4-week run-in period to
      receive placebo, or tadalafil 2.5 or 5 mg once daily for 14 days, followed by a
      14-day open label extension period of tadalafil 5 mg once daily. Primary analysis
      focused on the cumulative percent of men with a successful intercourse attempt
      during the first 4 days of treatment. On secondary analysis we evaluated the
      percent of successful attempts during the study. The Sexual Encounter Profile
      diary question 3 was used to assess efficacy. Safety was assessed by monitoring
      adverse events and vital signs. RESULTS: Significantly more men in the tadalafil
      5 mg group achieved successful intercourse, as indicated by a yes response to
      diary question 3, than those on placebo by day 2 (48.6% vs 36.6%, p < 0.025). The
      tadalafil 2.5 mg group did not separate from the placebo group on primary
      analysis. Secondary analysis showed that men on tadalafil 2.5 mg achieved a
      significantly higher percent of successful intercourse attempts than those on
      placebo by day 3 (35.5% vs 27.2%, p < 0.025). All groups further improved during
      the open label extension period. Tadalafil was well tolerated. CONCLUSIONS: This
      prospective trial shows the onset of efficacy of tadalafil 2.5 and 5 mg once
      daily within a few days of initiating therapy.

PMID- 21074804
TI  - The natural history and predictive factors of voided volume in older men: the
      Krimpen Study.
AB  - PURPOSE: Although functional bladder capacity, as expressed by maximum voided
      volume and other frequency-volume chart parameters, are important determinants of
      lower urinary tract symptoms, to our knowledge no population based data are
      available on changes in voided volume. We determined changes in and determinants
      of voided volume and voiding frequency with advancing age and with time, as
      measured by frequency-volume charts. MATERIALS AND METHODS: We performed a
      longitudinal, population based study in 1,688 men 50 to 78 years old with
      followup at 2.1, 4.2 and 6.5 years. Data were obtained using frequency-volume
      charts for maximum, 24-hour and average voided volume, and 24-hour voiding
      frequency as well as physical and urological measurements, and self-administered
      questionnaires. We used a linear mixed effect model to determine factors
      predicting volume changes. RESULTS: Median maximum and average voided volume
      decreased with time from 400 to 380 and 245 to 240 ml, respectively, and were
      smaller in older age groups while 24-hour voided volume showed no change. The 24
      hour voiding frequency increased with time and with advancing age. Maximum, 24
      hour and average voided volumes were positively related to alcohol intake.
      Maximum and average voided volumes were negatively related to higher age at
      baseline and the passage of time. Hypertension, diuretics and post-void residual
      volume were related to higher 24-hour voided volume. CONCLUSIONS: In older men
      maximum and average voided volume show a small but statistically significant
      decrease with time and with advancing age while 24-hour voided volume does not.
      Factors predicting the change in maximum or average voided volume are alcohol
      intake and higher age.

PMID- 21074805
TI  - Modified Clavien classification in percutaneous nephrolithotomy: assessment of
      complications in children.
AB  - PURPOSE: Although percutaneous nephrolithotomy has been accepted as an effective
      minimally invasive procedure in children, there is still no consensus on how to
      define and stratify complications by severity. MATERIALS AND METHODS: We
      retrospectively reviewed data of children who underwent percutaneous
      nephrolithotomy at our center between January 2002 and March 2010. A total of 100
      procedures were performed in 94 patients with a mean age of 9.5 years.
      Complications were recorded according to modified Clavien classification.
      RESULTS: Average stone burden ranged from 100 to 2,850 mm(2) (mean +/- SD 507.5
      +/- 475). Stones were located in the renal pelvis in 32 kidneys, calices in 20,
      renal pelvis and calices in 31, and upper ureter in 3. Stone-free rate after a
      single session of percutaneous nephrolithotomy was 85%. After auxiliary
      procedures in 7 cases stone-free rate increased to 89%. Grade I complications
      were seen in 7 patients postoperatively, grade II in 19 (hematuria requiring
      blood transfusion in 13 and nonseptic infection requiring antibiotics in 6) and
      grade III in 4 (hydrohemothorax in 2 and urine leakage requiring Double-J(r)
      stent in 2). No grade IV or V complications were observed. Regression analysis
      showed that stone burden (OR 1.006, 95% CI 1.001-1.011; p = 0.03) and operative
      time (OR 1.044, 95% CI 1.011-1.077; p = 0.009) were independent risk factors for
      complications. CONCLUSIONS: Percutaneous nephrolithotomy in children is safe,
      feasible and effective. Stone burden and operative time are independent risk
      factors for complications. The modified Clavien system provides a straightforward
      and validated method to classify postoperative complications.

PMID- 21074806
TI  - Editorial comment.

PMID- 21074807
TI  - Editorial comment.

PMID- 21074808
TI  - Diagnosis of the gr/gr Y chromosome microdeletion does not help in the treatment
      of infertile American men.
AB  - PURPOSE: The phenotypic effects of the gr/gr partial azoospermia factor c
      deletion vary geographically and to our knowledge have not been reported in the
      American population. We evaluated the clinical characteristics of infertile
      American men with the gr/gr deletion. MATERIALS AND METHODS: We retrospectively
      reviewed clinical data on 1,410 infertile men tested for the gr/gr deletion. We
      analyzed sperm concentration and the outcome of microdissection testicular sperm
      extraction with respect to gr/gr status. RESULTS: We identified 73 men with gr/gr
      deletions, including 43 of 989 (4.3%) with azoospermia, 18 of 317 (5.7%) with
      severe oligospermia (less than 5 million sperm per ml), 6 of 61 (9.8%) with
      oligospermia (5 to less than 20 million sperm per ml) and 6 of 43 (14%) infertile
      men with normospermia (greater than 20 million sperm per ml). A gr/gr deletion
      correlated with higher sperm production. The gr/gr deletion rate was higher in
      men with normospermia than in those with a sperm concentration of less than 20
      million and less than 5 million per ml (p = 0.021 and 0.006, respectively).
      Microdissection testicular sperm extraction was done in 22 azoospermic men with
      gr/gr deletions and sperm were retrieved in 14 (64%). This retrieval rate was
      similar to that at our center in men with idiopathic nonobstructive azoospermia
      (p = 0.13). CONCLUSIONS: Diagnosis of the gr/gr deletion did not predict impaired
      sperm production in our patient population and did not appear to alter the
      prognosis for surgical sperm retrieval. Despite the established modulatory impact
      of the gr/gr deletion on sperm production in some populations at this time the
      clinical value of testing infertile American men for the gr/gr deletion is not
      clear.

PMID- 21074809
TI  - New ureteral stent design does not improve patient quality of life: a randomized,
      controlled trial.
AB  - PURPOSE: Ureteral stents result in significant morbidity in many patients.
      Manufacturers have altered stent design and composition to minimize symptoms. The
      PolarisTM stent is made of a Percuflex(r) combination, providing a firm proximal
      aspect with a softer distal aspect to minimize symptoms. In this prospective,
      randomized study we compared symptoms and quality of life after stent insertion
      to determine whether this stent is better tolerated than the InLay(r) stent.
      MATERIALS AND METHODS: Between September 2002 and September 2006 we randomized
      159 patients requiring stent insertion for stone disease to receive the InLay or
      the Polaris ureteral stent. Patients were asked to complete the validated
      Ureteral Stent Symptom Questionnaire 2 weeks after stent insertion and 1 week
      after removal. RESULTS: A total of 98 patients completed and returned each
      questionnaire, including 45 with the InLay and 53 with the Polaris. There were no
      significant differences between the groups on any health domain assessed. In the
      InLay and Polaris groups 91% and 94% of patients experienced pain with the stent
      in situ, which decreased to 40% and 43%, respectively, after stent removal. The
      urinary symptom score with the stent in situ was equal in the 2 groups (32,
      maximum 55). Of the InLay and Polaris groups 60% and 66% of patients,
      respectively, would be against receiving a further stent due to symptoms (p =
      0.79). CONCLUSIONS: The Polaris stent, designed with the specific aim of
      improving urinary symptoms and pain associated with ureteral stents, continues to
      have a significant detrimental effect on patient quality of life.

PMID- 21074810
TI  - Durability of reusable holmium:YAG laser fibers: a multicenter study.
AB  - PURPOSE: Single use and reusable variants of holmium:YAG laser fibers are
      available to treat calculi during ureteroscopic procedures. In this prospective,
      multicenter study we evaluated a series of reusable holmium:YAG laser optical
      fibers. We hypothesized that reusable fibers provide a cost advantage over single
      use variants. MATERIALS AND METHODS: We prospectively recorded fiber data,
      including type, size, number of uses, laser pulse energy and frequency, and total
      energy delivered. All fibers were new and purchased off the shelf by staff at
      each institution. We performed a cost analysis comparing reusable fibers to
      single use variants. RESULTS: During 541 procedures a total of 37 holmium:YAG
      optical laser fibers were used, including 21 Laser Peripherals 270 (Laser
      Peripherals, Golden Valley, Minnesota), 7 Laser Peripherals 365, 4 Lumenis
      SlimLineTM 200 and 3 Lumenis SlimLine 365 fibers. After stratifying by core size
      365 MUm core fibers had significantly more uses than 270 MUm core fibers (average
      23.5 vs 11.3, p < 0.02). By fiber type the mean +/- SE number of uses was 12.8 +/
      2.44, 3 +/- 0.4, 21.3 +/- 7.12 and 28.7 +/- 6.69 for the Laser Peripheral 270,
      Lumenis SlimLine 200, Laser Peripherals 365 and Lumenis SlimLine 365,
      respectively. The total cost savings for reusable fibers vs single use variants
      was $64,125. CONCLUSIONS: Reusable holmium:YAG optical laser fibers are a more
      cost-effective option than single use variants. Fibers with a 365 MUm core
      provide more uses than smaller 270 MUm variants.

PMID- 21074811
TI  - The value of cytoreductive nephrectomy for metastatic renal cell carcinoma in the
      era of targeted therapy.
AB  - PURPOSE: We evaluated the value of cytoreductive nephrectomy in patients with
      metastatic renal cell carcinoma in the targeted therapy era. MATERIALS AND
      METHODS: We reviewed the records of 78 patients treated with targeted therapy for
      metastatic renal cell carcinoma between 2006 and 2009. A total of 45 patients
      underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive
      nephrectomy group) and 33 were treated with targeted therapy alone
      (noncytoreductive nephrectomy group). We estimated progression-free and overall
      survival using Kaplan-Meier curves. The prognostic significance of each variable
      was estimated with a Cox proportional hazards regression model. RESULTS:
      Clinicopathological variables did not differ in the 2 groups except for Karnofsky
      performance status and sarcomatoid feature. The treatment response rate did not
      differ in the 2 groups (23.1% vs 30.3%, p = 0.488). Median progression-free
      survival was 11.7 and 9.0 months in the cytoreductive and noncytoreductive
      nephrectomy groups (p = 0.270), and median overall survival was 21.6 and 13.9
      months, respectively (p = 0.128). On multivariate analysis Karnofsky performance
      status (HR 2.9, 95% CI 1.4-5.7, p = 0.003) and sarcomatoid features (HR 2.9, 95%
      1.3-6.7, p = 0.013) were independent predictors of progression-free survival.
      Karnofsky performance status (HR 3.3, 95% 1.7-6.5, p = 0.001), sarcomatoid
      features (HR 2.7, 95% 1.2-6.2, p = 0.021) and liver metastasis (HR 2.7, 95% 1.0
      7.1, p = 0.045) were independent predictors of overall survival. CONCLUSIONS: We
      found no significant differences in tumor response or survival between the 2
      groups. Prospective trials are needed to confirm our results.

PMID- 21074812
TI  - Editorial comment.

PMID- 21074813
TI  - Combined use of late phase dimercapto-succinic acid renal scintigraphy and
      ultrasound as first line screening after urinary tract infection in children.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of
      dimercapto-succinic acid renal scintigraphy and renal ultrasound in identifying
      high grade vesicoureteral reflux in children after a first episode of urinary
      tract infection. MATERIALS AND METHODS: A total of 533 children following a first
      urinary tract infection were included in the analysis. Patients were assessed by
      3 diagnostic imaging studies, renal ultrasound, dimercapto-succinic acid scan and
      voiding cystourethrography. The main event of interest was the presence of high
      grade (III to V) vesicoureteral reflux. The combined and separate diagnostic
      accuracy of screening methods was assessed by calculation of diagnostic OR,
      sensitivity, specificity, positive predictive value, negative predictive value
      and likelihood ratio. RESULTS: A total of 246 patients had reflux, of whom 144
      (27%) had high grade (III to V) disease. Sensitivity, negative predictive value
      and diagnostic OR of ultrasound for high grade reflux were 83.3%, 90.8% and 7.9,
      respectively. Dimercapto-succinic acid scan had the same sensitivity as
      ultrasound but a higher negative predictive value (91.7%) and diagnostic OR
      (10.9). If both tests were analyzed in parallel by using the OR rule, ie a
      negative diagnosis was established only when both test results were normal,
      sensitivity increased to 97%, negative predictive value to 97% and diagnostic OR
      to 25.3. Only 9 children (6.3%) with dilating reflux had an absence of
      alterations in both tests. CONCLUSIONS: Our findings support the idea that
      ultrasound and dimercapto-succinic acid scan used in combination are reliable
      predictors of dilating vesicoureteral reflux.

PMID- 21074814
TI  - [Pharmaco-economic optimization of cholesterol-lowering treatment with statins].
AB  - Current guidelines for the management of hypercholesterolemia identify LDL
      cholesterol (LDL-c) reduction as the primary therapeutic target and have
      highlighted the need to use statins to achieve it. There are six statins with
      four different doses and with different power-reducing LDL-c. By adding
      ezetimibe, there are 48 therapeutic possibilities. This extensive offer provides
      pharmaceutical treatment, but it is difficult to choose the most cost-effective
      statin because it is very difficult to remember all the powers and costs of
      treatment options. This paper offers a method to prioritize the best cost
      effective lipid lowering, and chooses the cheapest statin that achieves the
      desired therapeutic goal of LDL-c.

PMID- 21074815
TI  - [Clinical use of D-dimer in patients with cancer].
AB  - There is a well-known close relationship between cancer and the haemostatic
      system. Plasma D-dimer (DD) is a marker of fibrin generation and lysis. In the
      clinical practice, its main use is in the diagnostic algorithms of venous
      thromboembolism (VTE), and it is one of the diagnostic criteria of disseminated
      intravacular coagulation. In patients with cancer, the specificity of DD is lower
      than in the general population, reducing its usefulness. However, there is a
      growing evidence that points out a possible application of DD in the clinical
      management of cancer patients as a predictor of VTE, marker of hidden cancer in
      patients with idiopathic VTE, or even as an independent prognostic factor of
      response to chemotherapy and survival. In this review, the current evidence
      supporting the use of DD in cancer patients is critically exposed and discussed.

PMID- 21074816
TI  - [The importance of hospital discharge report].

PMID- 21074817
TI  - [C-reactive protein: a biomarker in primary care].

PMID- 21074818
TI  - Tomato-produced 7-epizingiberene and R-curcumene act as repellents to whiteflies.
AB  - How whiteflies (Bemisia tabaci) make the choice for a host plant prior to
      landing, is not precisely known. Here we investigated whether they respond to
      specific volatiles of tomato. Zingiberene and curcumene were purified from
      Solanum habrochaites (PI127826), characterised by NMR and X-ray analysis and
      identified as 7-epizingiberene and R-curcumene. In contrast, oil from Zingiber
      officinalis contained the stereoisomers zingiberene and S-curcumene,
      respectively. Using a combination of free-choice bio-assays and
      electroantennography, 7-epizingiberene and its dehydrogenated derivative R
      curcumene were shown to be active as semiochemicals to B. tabaci adults, whereas
      the stereoisomers from ginger were not. In addition, R-curcumene elicited the
      strongest electroantennographic response. Bio-assays showed that a cultivated
      tomato could be made less attractive to B. tabaci than its neighbouring siblings
      by the addition of the tomato stereoisomer 7-epizingiberene or its derivative R
      curcumene. These sesquiterpenes apparently repel adult whiteflies prior to
      landing, presumably because it informs them that after landing they, or their
      offspring, may be exposed to higher and lethal concentrations of the same
      compounds.

PMID- 21074819
TI  - Photodynamic therapy of choroidal hemangioma in sturge-weber syndrome, with a
      review of treatments for diffuse and circumscribed choroidal hemangiomas.
AB  - We report three new cases of patients with Sturge-Weber Syndrome and symptomatic
      retinal detachments from diffuse choroidal hemangiomas successfully treated with
      photodynamic therapy (PDT) and review medical literature on the available
      treatment options for choroidal hemangiomas. All patients were treated with a
      single session of PDT with verteporfin infused at a concentration of 6 mg/m(2)
      and treated for 83 seconds with 689-nm Zeiss laser that was delivered with total
      energy level of 50 J/cm(2) with an intensity of 600 mW/cm(2). The exudative
      retinal detachment (RD) and macular edema completely resolved in all cases by 1-4
      months after PDT treatment. Visual acuity improved in all three cases with
      diminished tumor size in the areas of treatment. One case was followed for 5
      months, another for 2 years, and the third case for 6 years, with no recurrence
      of exudative RD. PDT is an effective treatment option for visual deterioration
      from exudative retinal detachment in patients with diffuse choroidal hemangiomas.

PMID- 21074820
TI  - Ozonation and activated carbon treatment of sewage effluents: removal of
      endocrine activity and cytotoxicity.
AB  - Concerns about endocrine disrupting compounds in sewage treatment plant (STP)
      effluents give rise to the implementation of advanced treatment steps for the
      elimination of trace organic contaminants. The present study investigated the
      effects of ozonation (O(3)) and activated carbon treatment (AC) on endocrine
      activities [estrogenicity, anti-estrogenicity, androgenicity, anti-androgenicity,
      aryl-hydrocarbon receptor (AhR) agonistic activity] with yeast-based bioassays.
      To evaluate the removal of non-specific toxicity, a cytotoxicity assay using a
      rat cell line was applied. Wastewater (WW) was sampled at two STPs after
      conventional activated sludge treatment following the secondary clarifier (SC)
      and after subsequent advanced treatments: O(3), O(3) + sand filtration (O(3-SF)),
      and AC. Conventional treatment reduced estrogenicity, androgenicity, and AhR
      agonistic activity by 78-99% compared to the untreated influent WW. Anti
      androgenicity and anti-estrogenicity were not detectable in the influent but
      appeared in SC, possibly due to the more effective removal of respective agonists
      during conventional treatment. Endocrine activities after SC ranged from 2.0 to
      2.8 ng/L estradiol equivalents (estrogenicity), from 4 to 22 MUg/L 4
      hydroxytamoxifen equivalents (anti-estrogenicity), from 1.9 to 2.0 ng/L
      testosterone equivalents (androgenicity), from 302 to 614 MUg/L flutamide
      equivalents (anti-androgenicity), and from 387 to 741 ng/L beta-naphthoflavone
      equivalents (AhR agonistic activity). In particular, estrogenicity and anti
      androgenicity occurred in environmentally relevant concentrations. O(3) and AC
      further reduced endocrine activities effectively (estrogenicity: 77-99%, anti
      androgenicity: 63-96%, AhR agonistic activity: 79-82%). The cytotoxicity assay
      exhibited a 32% removal of non-specific toxicity after O(3) compared to SC. O(3)
      and sand filtration reduced cytotoxic effects by 49%, indicating that sand
      filtration contributes to the removal of toxicants. AC was the most effective
      technology for cytotoxicity removal (61%). Sample evaporation reduced cytotoxic
      effects by 52 (AC) to 73% (O(3)), demonstrating that volatile substances
      contribute considerably to toxic effects, particularly after O(3). These results
      confirm an effective removal or transformation of toxicants with receptor
      mediated mode of action and non-specific toxicants during O(3) and AC. However,
      due to the limited extractability, polar ozonation by-products were neglected for
      toxicity analysis, and hence non-specific toxicity after O(3) is underestimated.

PMID- 21074821
TI  - Ultraviolet absorption properties of suspended particulate matter in untreated
      surface waters.
AB  - Previous research has shown that wastewater disinfection using UV light can be
      impaired by attenuation of the UV light as it passes through particles to reach
      embedded and protected microorganisms. This study determined that the UV
      absorption (at 254 nm) of particles present in 10 untreated surface waters was
      similar to the absorption of wastewater particles. As such, it provides evidence
      that UV disinfection of surface waters during drinking water treatment may be
      impaired by the same mechanism if particles are present. The study also
      demonstrated that among the 10 untreated surface waters examined, there was no
      correlation between the UV absorption (254 nm) of the solid particulate material,
      total organic carbon, total suspended solids, turbidity, or UV absorbance (254)
      of the bulk water.

PMID- 21074822
TI  - Evaluation on the toxicity of ionic liquid mixture with antagonism and synergism
      to Vibrio qinghaiensis sp.-Q67.
AB  - Ionic liquids (ILs) are a fascinating group of new chemicals with the potential
      to replace the classical volatile organic solvents, stimulating many applications
      in chemical industry. In case ILs are released to the environment, possible
      combined toxicity should be taken into account and it is, however, often
      neglected up to now. In this paper, therefore, the concentration-response curves
      (CRCs) of four groups of IL mixtures with various mixture ratios to Vibrio
      qinghaiensis sp.-Q67 were determined using the microplate toxicity analysis and
      were compared to the CRCs predicted by an additive reference model, the
      concentration addition (CA) or independent action (IA), to identify the toxicity
      interaction. It is showed that most of the IL mixture rays displayed the
      classical addition while the remaining rays exhibited antagonism or synergism.
      Moreover, it is found that the pEC50 values of the mixture rays exhibiting
      antagonism or synergism are well correlated with the mixture ratio of a certain
      IL therein.

PMID- 21074823
TI  - Evaluation of a novel high throughput screening tool for relative emissions of
      industrial chemicals used in chemical products.
AB  - Tens of thousands of chemicals are currently marketed worldwide, but only a small
      number of these compounds has been measured in effluents or the environment to
      date. The need for screening methodologies to select candidates for environmental
      monitoring is therefore significant. To meet this need, the Swedish Chemicals
      Agency developed the Exposure Index (EI), a model for ranking emissions to a
      number of environmental matrices based on chemical quantity used and use pattern.
      Here we evaluate the EI. Data on measured concentrations of organic chemicals in
      sewage treatment plants, one of the recipients considered in the EI model, were
      compiled from the literature, and the correlation between predicted emission
      levels and observed concentrations was assessed by linear regression analysis.
      The adequacy of the parameters employed in the EI was further explored by
      calibration of the model to measured concentrations. The EI was found to be of
      limited use for ranking contaminant levels in STPs; the r2 values for the
      regressions between predicted and observed values ranged from 0.02 (p = 0.243) to
      0.14 (p = 0.007) depending on the dataset. The calibrated version of the model
      produced only slightly better predictions although it was fitted to the
      experimental data. However, the model is a valuable first step in developing a
      high throughput screening tool for organic contaminants, and there is potential
      for improving the EI algorithm.

PMID- 21074824
TI  - Dechlorination of PCBs in the simulative transformer oil by microwave
      hydrothermal reaction with zero-valent iron involved.
AB  - The conventional hydrothermal reaction with iron powder, NaOH and H(2)O as
      reactants was reported to occur at temperature above 423K, and iron oxides
      (Fe(3)O(4) and NaFeO(2)) and hydrogen were produced. In this study, microwave
      heating was adopted to take the place of conventional heating to induce the
      hydrothermal reaction. Under microwave irradiation, NaOH and H(2)O absorbed
      microwave energy by space charge polarization and dipolar polarization and
      instantly converted it into thermal energy, which initiated the hydrothermal
      reaction that involved with zero-valent iron. X-ray diffraction (XRD) analysis
      found Fe(3)O(4)/NaFeO(2) and confirmed the occurrence of microwave-induced
      hydrothermal reaction. The developed microwave-hydrothermal reaction was employed
      for the dechlorination of PCBs. Hexadecane containing 100mgL(-1) of Aroclor1254
      was used as simulative transformer oil, and the dechlorination of PCBs was
      evaluated by GC/ECD, GC/MS and ion chromatography. For PCBs in 10mL simulative
      transformer oil, almost complete dechlorination was achieved by 750W microwave
      irradiation for 10min, with 0.3g iron powder, 0.3g NaOH and 0.6mL H(2)O added.
      The effects of important factors including microwave power and the amounts of
      reactants added, on the dechlorination degree were investigated, moreover, the
      dechlorination mechanism was suggested. Microwave irradiation combined with the
      common and cheap materials, iron powder, NaOH and H(2)O, might provide a fast and
      cost-effective method for the treatment of PCBs-containing wastes.

PMID- 21074825
TI  - Treatment of dynamic mixture of hexane and benzene vapors in a Trickle Bed Air
      Biofilter integrated with cyclic adsorption/desorption beds.
AB  - One of the main challenges that face successful biofiltration is the erratic
      loading pattern and long starvation periods. However, such patterns are common in
      practical applications. In order to provide long-term stable operation of a
      biofilter under these conditions, a cyclic adsorption/desorption beds system with
      flow switching was installed prior to a biofilter. Different square waves of a
      mixture containing n-hexane and benzene at a 2:1 ratio were applied to the cyclic
      adsorption/desorption beds and then fed to a biofilter. The performance of this
      integrated system was compared to a biofilter unit receiving the same feed of
      both VOCs. The cyclic adsorption/desorption beds unit successfully achieved its
      goal of stabilizing erratic loading even with very sharp peaks at the influent
      concentration equalizing influent concentrations ranging from 10-470 ppmv for n
      hexane to 30-1410 ppmv for benzene. The study included different peak
      concentrations with durations ranging from 6 to 20 min. The cyclic beds buffered
      the fluctuating influent load and the followed biofilter had all the time a
      continuous stable flow. Another advantage achieved by the cyclic
      adsorption/desorption beds was the uninterrupted feed to the biofilter even
      during the starvation where there was no influent in the feed. The results of the
      integrated system with regard to removal efficiency and kinetics are comparable
      to published results with continuous feed studies at the same loading rates. The
      removal efficiency for benzene had a minimum of 85% while for n-hexane ranged
      from 50% to 77% according to the loading rate. The control unit showed very
      erratic performance highlighting the benefit of the utilization of the cyclic
      adsorption/desorption beds. The biofilter was more adaptable to concentration
      changes in benzene than n-hexane.

PMID- 21074826
TI  - Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and
      diabetic nephropathy in an African American homozygous for MYH9 risk variants.
AB  - Familial clustering of disparate kidney diseases including clinically diagnosed
      hypertensive and diabetic nephropathy, idiopathic focal segmental
      glomerulosclerosis, and HIV-associated nephropathy are often observed in African
      Americans. Admixture mapping recently identified the nonmuscle myosin heavy chain
      9 gene (MYH9) as a susceptibility factor strongly associated with several
      nondiabetic etiologies of end-stage renal disease in African Americans, less
      strongly with diabetes-associated end-stage renal disease. MYH9-associated
      nephropathies reside in the spectrum of focal segmental glomerulosclerosis/focal
      global glomerulosclerosis. The renal histology in proteinuric African Americans
      homozygous for MYH9 risk variants with longstanding type 2 diabetes mellitus is
      unknown. We report a case of coincident idiopathic focal segmental
      glomerulosclerosis collapsing variant and diabetic nephropathy in an African
      American homozygous for the MYH9 E1 risk haplotype. This case demonstrates that
      diabetic African Americans with overt proteinuria can have mixed renal lesions,
      including those in the spectrum of MYH9-associated nephropathy. Careful
      interpretation of kidney biopsies in proteinuric African Americans with diabetes
      is necessary to exclude coincident nondiabetic forms of nephropathy, precisely
      define etiologies of kidney disease, and determine the natural history and
      treatment response in mixed lesions of diabetes-associated and MYH9-associated
      kidney disease.

PMID- 21074827
TI  - Preliminary notes on a newly discovered skull of the extinct monkey Antillothrix
      from Hispaniola and the origin of the Greater Antillean monkeys.

PMID- 21074828
TI  - Relationships between the expression of the stapedial artery and the size of the
      obturator foramen in euarchontans: Functional and phylogenetic implications.
AB  - Cranial arterial patterns are commonly used for determining phylogenetic patterns
      in extant taxa and have often been used in studies investigating the
      relationships among fossil taxa. In primitive eutherians, the stapedial artery
      provided blood to the meninges, orbits, and certain regions of the face. In many
      modern mammals, however, blood supply to most of these areas has been taken over
      by branches of the external carotid, although some groups (e.g., treeshrews, some
      families of primates) still retain aspects of the ancestral pattern. Here, we
      show that the relative size of the obturator foramen of the stapes is a reliable
      indicator of the presence or absence of a "functional" stapedial artery in
      Euarchonta. We also describe newly discovered stapedes for extinct euarchontans,
      Ignacius graybullianus, and Plesiadapis tricuspidens, and use the approach
      described here to show that these taxa likely did not have a functional stapedial
      artery. The implications of these findings for auditory function and phylogenetic
      studies are discussed.

PMID- 21074829
TI  - Metatarsal fusion pattern and developmental morphology of the Olduvai Hominid 8
      foot: Evidence of adolescence.
AB  - The morphology of the Olduvai Hominid (OH) 8 foot and the sequence of metatarsal
      epiphyseal fusion in modern humans and chimpanzees support the hypothesis that OH
      8 belonged to an individual of approximately the same relative age as the OH 7
      subadult, the holotype of Homo habilis. Modern humans and chimpanzees exhibit a
      variety of metatarsal epiphyseal fusion patterns, including one identical to that
      observed in OH 8 in which metatarsal 1 fuses before metatarsals 2-5. More than
      the metatarsal fusion sequence, however, the principal evidence of the youthful
      age of OH 8 lies in the morphology of metatarsals 1, 2, and 3. Because both OH 8
      and OH 7 come from the same stratum at the FLK NN type site, the most
      parsimonious explanation of the OH 8 and OH 7 data is that this material belonged
      to the same individual, as originally proposed by Louis Leakey. The proposition
      that OH 8 belonged to an adult is unsupported by morphology, including
      radiographic evidence, and the fusion sequences in human and chimpanzee skeletal
      material reported here and in the literature.

PMID- 21074830
TI  - Neonatal systemic venous thrombosis.
AB  - The incidence of thrombotic events is higher in neonates compared to children of
      other age groups. Perinatal and maternal risk factors, as well as the developing
      neonatal hemostatic system, are contributing factors in the higher rate of
      thrombosis in this pediatric population. This review summarizes the available
      literature to date and gives an updated overview of the systemic venous
      thrombosis in neonates including clinical presentation, risk factors, recommended
      treatment modalities and associated outcomes.

PMID- 21074831
TI  - Analysis of co-expression of OCT4, NANOG and SOX2 in pluripotent cells of the
      porcine embryo, in vivo and in vitro.
AB  - To derive porcine embryonic stem (ES) cell lines, the time window during which
      porcine embryos contain pluripotent cells that are predisposed to
      undifferentiated self-renewal in vitro must be identified. Therefore we first
      studied the spatial and temporal expression pattern of key factors in
      pluripotency and lineage segregation of blastocyst-stage porcine embryos between
      embryonic days (E) 6.5 and E10.5 using whole mount in situ hybridization,
      quantitative reverse transcription (RT)-PCR and whole mount immunofluorescence.
      Expression of NANOG and SOX2 was detected in both the ICM and epiblast, while
      OCT4 expression became restricted to the epiblast at E9.5. Surprisingly ICM and
      epiblast cells also expressed CK18. Consequently, growth factors which sustain
      the undifferentiated growth of human ES cells and mouse epiblast stem cells
      (EpiSCs) were tested for their ability to sustain undifferentiated self-renewal
      of porcine ICM and epiblast cells in vitro. Cultures of ICM cells resulted in a
      higher percentage of primary colonies with an ES-like morphology compared to
      primary cultures derived from epiblast cells. These undifferentiated colonies
      sustained expression of OCT4, NANOG, SOX2 and CK18. The expression of CK18
      suggests that these cells are more similar to human ES cells and mouse EpiSCs
      than to mouse ES cells. Although undifferentiated cultures were maintained for
      limited passages, ICM and epiblast cultures rapidly differentiated into cell
      types of mesodermal, ectodermal, and endodermal origin, as characterized by RT
      PCR. These results demonstrate that porcine ICM and epiblast cells can not be
      cultured in vitro with currently used human ES cell culture conditions.
      Importantly however, the trio of OCT4, NANOG and SOX2, which are known to form an
      autoregulatory network for pluripotency in other systems, are co-expressed also
      by porcine epiblasts, and by undifferentiated primary colonies in culture.

PMID- 21074832
TI  - Cloacal gland foam enhances motility and disaggregation of spermatozoa in
      Japanese quail (Coturnix japonica).
AB  - The adult male Japanese quail produces white foam from the cloacal gland, which
      is transferred to the female proctodeum during natural mating. The physiological
      role of foam on quail spermatozoa is still unclear. Therefore, attempts have been
      made to understand the effect of cloacal foam on motility and metabolism of quail
      spermatozoa. The profile of various biochemical constitutes in the foam extract
      was investigated. The addition of foam extract to neat semen completely
      disaggregated the clumps of spermatozoa leading to vigorous motility. The
      metabolic rate (MBRT) of the spermatozoa was significantly increased with the
      addition of foam extract. The foam extract was sub fractionated into seven
      different fractions by using the molecular cut off devices. Among all the seven
      sub-fractions from the foam extract, the addition of < 1 KDa sub-fraction
      contained lactate and has enhanced sperm motility and metabolism. Another
      fraction (3-10 KDa) has non-protein and non-heparin components which completely
      disaggregated the clumped quail spermatozoa. However, the remaining fractions did
      not show any effect on quail spermatozoa. It can be concluded from the present
      investigation that the lactate present in foam might be a fuel for sperm
      metabolism and motility. Furthermore, low molecular weight (3-10 KDa) components
      in the foam may responsible for sperm disaggregation.

PMID- 21074833
TI  - Fecal progesterone metabolites and ovarian activity in cycling and pregnant
      mountain gazelles (Gazella gazella).
AB  - Fecal reproductive progestagen monitoring in the mountain gazelle (Gazella
      gazella) provided a non-invasive method for tracking reproductive cycling,
      estimating age of sexual maturity and diagnosing pregnancy in this species of
      gazelle. Fresh fecal samples were collected from eight female mountain gazelle
      (Gazella gazella) for a period of two months. Two of the animals were pregnant
      while the other six were not. Using the progestagen profile the luteal phase,
      interluteal (follicular) phase and estrous cycle in adult female gazelles were
      determined to be 12.5 +/- 1.2, 5.9 +/- 0.59 and 18.8 +/- 0.98 days respectively.
      Significant inter-animal differences in fecal progestagen concentration were
      observed in both the luteal and follicular phases. Significant differences were
      observed in the levels of fecal progestagen between cycling females and females
      in late pregnancy. Low concentrations of fecal progestagen in females aged less
      than 18 months old indicated that sexual maturity in captivity is not attained
      before that age.

PMID- 21074834
TI  - Mitochondrial distribution and meiotic progression in canine oocytes during in
      vivo and in vitro maturation.
AB  - The objective was to evaluate mitochondrial distribution, and its relationship to
      meiotic development, in canine oocytes during in vitro maturation (IVM) at 48,
      72, and 96 h, compared to those that were non-matured or in vivo matured
      (ovulated). The distribution of active mitochondria during canine oocyte
      maturation (both in vitro and in vivo) was assessed with fluorescence and
      confocal microscopy using MitoTracker Red (MT-Red), whereas chromatin
      configuration was concurrently evaluated with fluorescence microscopy and DAPI
      staining. During IVM, oocytes exhibited changes in mitochondrial organization,
      ranging from a fine uniform distribution (pattern A), to increasing clustering
      spread throughout the cytoplasm (pattern B), and to a more perinuclear and
      cortical distribution (pattern C). Pattern A was mainly observed in germinal
      vesicle (GV) oocytes (96.4%), primarily in the non-matured group (P < 0.05).
      Pattern B was seen in all ovulated oocytes which were fully in second metaphase
      (MII), whereas in IVM oocytes, ~64% were pattern B, irrespective of duration of
      culture or stage of nuclear development (P > 0.05). Pattern C was detected in a
      minor percentage (P < 0.05) of oocytes (mainly those in first metaphase, MI)
      cultured for 72 or 96 h. In vitro matured oocytes had a minor percentage of
      pattern B (P < 0.05) and smaller mitochondrial clusters in IVM oocytes than
      ovulated oocytes, reaching only 4, 11, and 17% of MII at 48, 72, and 96 h,
      respectively. Thus, although IVM canine oocytes rearranged mitochondria, which
      could be related to nuclear maturation, they did not consistently proceed to MII,
      perhaps due to incomplete IVM, confirming that oocytes matured in vitro were less
      likely to be competent than those matured in vivo.

PMID- 21074835
TI  - Is photometry an accurate and reliable method to assess boar semen concentration?
AB  - Sperm concentration assessment is a key point to insure appropriate sperm number
      per dose in species subjected to artificial insemination (AI). The aim of the
      present study was to evaluate the accuracy and reliability of two commercially
      available photometers, AccuCellTM and AccuReadTM pre-calibrated for boar semen in
      comparison to UltiMateTM boar version 12.3D, NucleoCounter SP100 and Thoma
      hemacytometer. For each type of instrument, concentration was measured on 34 boar
      semen samples in quadruplicate and agreement between measurements and instruments
      were evaluated. Accuracy for both photometers was illustrated by mean of
      percentage differences to the general mean. It was -0.6% and 0.5% for AccucellTM
      and AccureadTM respectively, no significant differences were found between
      instrument and mean of measurement among all equipment. Repeatability for both
      photometers was 1.8% and 3.2% for AccuCellTM and AccuReadTM respectively. Low
      differences were observed between instruments (confidence interval 3%) except
      when hemacytometer was used as a reference. Even though hemacytometer is
      considered worldwide as the gold standard, it is the more variable instrument
      (confidence interval 7.1%). The conclusion is that routine photometry measures of
      raw semen concentration are reliable, accurate and precise using AccuReadTM or
      AccuCellTM. There are multiple steps in semen processing that can induce sperm
      loss and therefore increase differences between theoretical and real sperm
      numbers in doses. Potential biases that depend on the workflow but not on the
      initial photometric measure of semen concentration are discussed.

PMID- 21074836
TI  - Biosynthesis of hamster zona pellucida is restricted to the oocyte.
AB  - The zona pellucida (ZP) is an extracellular coat that surrounds the mammalian
      oocyte and the early embryo until implantation. This coat mediates several
      critical aspects of fertilization, including species-selective sperm recognition,
      the blocking of polyspermy and protection of the oocyte and the preimplantation
      embryo. Depending on the species, the ZP is composed of three to four different
      glycoproteins encoded by three or four genes. These genes have been cloned and
      sequenced for different species. However, controversy exists about the cell type
      specificity of the ZP glycoproteins, for which several models have been proposed.
      Different groups have reported that ZP is produced only by the oocytes, by the
      granulosa cells or by both cell types, depending on the species under study. We
      recently described the expression of four ZP proteins in the hamster ovary. By
      means of the complete set of the hamster ZP cDNAs, we undertook the study of the
      origin and expression pattern of the four ZP genes. In the present work, the
      expression of ZP1, ZP2, ZP3 and ZP4 is carefully analyzed by in situ
      hybridization (ISH) in hamster ovaries. Our data suggest that the four hamster ZP
      genes are expressed in a coordinate and oocyte-specific manner during
      folliculogenesis. Furthermore, this expression is maximal during the first stages
      of the oocyte development and declines in oocytes from later development stages,
      particularly within large antral follicles.

PMID- 21074837
TI  - Demecolcine- and nocodazole-induced enucleation in mouse and goat oocytes for the
      preparation of recipient cytoplasts in somatic cell nuclear transfer procedures.
AB  - Treatment of pre-activated oocytes with demecolcine (DEM) has been shown to
      induce the extrusion of all oocyte chromosomes within the second polar body
      (PB2). However, induced enucleation (IE) rates are generally low and the
      competence of these cytoplasts to support embryonic development following somatic
      cell nuclear transfer (SCNT) is impaired. Here, we explored whether short
      treatments with DEM or another antimitotic, nocodazole (NOC), improve IE
      efficiency, and determined the most appropriate timing for nuclear transfer in
      the cytoplasts produced. We show, for the first time, that IE can be accomplished
      in mouse and goat oocytes using NOC and that short treatments with DEM or NOC
      result in similar IE rates, which proved to be strain- and species-specific.
      Because enucleation induced by both antimitotic drugs is reversible, the IE
      protocol was combined with the mechanical aspiration of PB2s to increase
      permanent enucleation rates in mouse oocytes. None of the cloned mouse embryos
      produced from the resultant cytoplasts developed to the blastocyst stage.
      However, when they were reconstructed prior to the activation and antimitotic
      treatment, their in vitro embryonic development was similar to that of cloned
      embryos produced from mechanically-enucleated oocytes.

PMID- 21074838
TI  - Characterization of lactate dehydrogenase enzyme in seminal plasma of Japanese
      quail (Coturnix coturnix japonica).
AB  - Lactate dehydrogenase enzyme present in quail seminal plasma has been
      characterized. Polyacrylamide gel electrophoresis and subsequently with LDH
      specific staining of seminal plasma revealed a single isozyme in quail semen.
      Studies on substrate inhibition, pH for optimum activity and inhibitor (urea)
      indicated the isozyme present in the quail semen has catalytic properties like
      LDH-1 viz. H-type. Furthermore, unlike other mammalian species, electrophoretic
      and kinetic investigations did not support the existence of semen specific LDH-X
      isozyme in quail semen. The effect of exogenous lactate and pyruvate on sperm
      metabolic activity was also studied. The addition of 1 mM lactate or pyruvate to
      quail semen increased sperm metabolic activity. Our results suggested that both
      pyruvate and lactate could be used by quail spermatozoa to maintain their basic
      functions. Since the H-type isozyme is important for conversion of lactate to
      pyruvate under anaerobic conditions it was postulated that exogenous lactate
      being converted into pyruvate via LDH present in semen may be used by sperm
      mitochondria to generate ATP. During conversion of lactate to pyruvate NADH is
      being generated that may be useful for maintaining sperm mitochondrial membrane
      potential.

PMID- 21074839
TI  - Acetylation of H4K12 in porcine oocytes during in vitro aging: potential role of
      ooplasmic reactive oxygen species.
AB  - Deterioration in the quality of mammalian mature oocytes during metaphase-II (M
      II) arrest is called "oocyte aging". Although histone acetylation may affect the
      progression of aging in murine oocytes, the mechanism is unknown. The objective
      was to determine the role of ooplasmic reactive oxygen species (ROS) in
      acetylation of histone H4 at lysine 12 (acH4K12) in porcine aged oocytes in
      vitro. Based on immunostaining with a specific antibody, acetylation of H4K12 in
      porcine oocytes increased during in vitro aging, which coincided with changing
      patterns of ooplasmic ROS content. Furthermore, both hydrogen peroxide
      (H(2)O(2)), and the mitochondrial membrane potential disrupter, carbonyl cyanide
      3-chlorophenylhydrazone (CCCP), which can moderately elevate oocyte ROS content,
      significantly increased acetylation levels of H4K12 in porcine oocytes. It was
      noteworthy that acetylation in the CCCP group was decreased when ROS was
      counteracted by cysteine, a common antioxidant. In addition, the intracellular
      mRNA abundance of acetyltransferase gene HAT1 in aged and H(2)O(2) treated
      oocytes was higher than in M-II phase oocytes, suggesting that HAT1 was involved
      in this reaction. After parthenogenetic activation, a lower proportion of oocytes
      developed to the blastocyst stage after CCCP or H(2)O(2) treatment when compared
      with M-II phase oocytes (20 and 0% for CCCP and H(2)O(2) groups, respectively,
      versus 42% for the M-II group, P < 0.05). In conclusion, elevated levels of H4K12
      acetylation were attributed to increased ooplasmic ROS content during porcine
      oocyte aging in vitro.

PMID- 21074840
TI  - Cooling of pacu (Piaractus mesopotamicus) embryos at various stages of
      development for 6 or 10 hours.
AB  - The objective of this research was to verify the effects of cooling embryos of
      pacu, Piaractus mesopotamicus, in four stages of development during two stocking
      periods. The stages of embryo development were at: blastoderm, ~ 64 cells-1.4 h
      after fertilization (haf); 25% of the epiboly movement--5.2 haf; blastoporous
      closing--8.0 haf; and optical vesicle appearing--13.3 haf. Embryos were exposed
      to a cryoprotectant solution containing methanol (10%) and sucrose (0.5 M).
      Thereafter, embryos were submitted to a cooling curve until they reached -8 
      degrees C, and then kept cooled for 6 or 10 h. In addition, for each stage of
      embryonic development, a control group with uncooled embryos was used to compare
      hatching rates. The total number of larvae from the first two stages of
      ontogenetic development (1.4 and 5.2 haf) was lower compared to the other stages
      (0.0 and 8.0 haf). There was no significant difference between stages 8.0 and
      13.3 haf for the total number of larvae (49.9 +/- 6.7% and 55.2 +/- 6.7%,
      respectively). Embryo diameter varied according to embryonic stage, providing
      evidence of differences in membrane permeability. There was a negative
      correlation between embryo diameter and the total number of larvae (r = -0.372).
      In conclusion, use of embryonic stages 8.0 and 13.3 haf were recommended for
      maintaining cooled pacu embryos at -8  degrees C for 6 or 10 h.

PMID- 21074841
TI  - Specific coping behaviors in relation to adolescent depression and suicidal
      ideation.
AB  - The coping strategies used by adolescents to deal with stress may have
      implications for the development of depression and suicidal ideation. This study
      examined coping categories and specific coping behaviors used by adolescents to
      assess the relation of coping to depression and suicidal ideation. In
      hierarchical regression models, the specific coping behaviors of behavioral
      disengagement and self-blame were predictive of higher levels of depression;
      depression and using emotional support were predictive of suicidal ideation.
      Results suggest that specific behaviors within the broad coping categories of
      emotion-focused coping (e.g., self-blame) and avoidant coping (e.g., behavioral
      disengagement) account for these categories' associations with depression and
      suicidal ideation. Specific problem-focused coping strategies did not
      independently predict lower levels of depression or suicidal ideation. It may be
      beneficial for interventions to focus on eliminating maladaptive coping behaviors
      in addition to introducing or enhancing positive coping behaviors.

PMID- 21074842
TI  - The English strategy to reduce health inequalities.

PMID- 21074843
TI  - High-density collagen gel tubes as a matrix for primary human bladder smooth
      muscle cells.
AB  - Tissue-engineered grafts for the urinary tract are being investigated for the
      potential treatment of several urologic diseases. These grafts, predominantly
      tubular-shaped, usually require in vitro culture prior to implantation to allow
      cell engraftment on initially cell-free scaffolds. We have developed a method to
      produce tubular-shaped collagen scaffolds based on plastic compression. Our
      approach produces a ready cell-seeded graft that does not need further in vitro
      culture prior to implantation. The tubular collagen scaffolds were in particular
      investigated for their structural, mechanical and biological properties. The
      resulting construct showed an especially high collagen density, and was
      characterized by favorable mechanical properties assessed by axial extension and
      radial dilation. Young modulus in particular was greater than non-compressed
      collagen tubes. Seeding densities affected proliferation rate of primary human
      bladder smooth muscle cells. An optimal seeding density of 10(6) cells per
      construct resulted in a 25-fold increase in Alamar blue-based fluorescence after
      2 wk in culture. These high-density collagen gel tubes, ready seeded with smooth
      muscle cells could be further seeded with urothelial cells, drastically
      shortening the production time of graft for urinary tract regeneration.

PMID- 21074844
TI  - The therapeutic potential of human multipotent mesenchymal stromal cells combined
      with pharmacologically active microcarriers transplanted in hemi-parkinsonian
      rats.
AB  - Multipotent mesenchymal stromal cells (MSCs) raise great interest for brain cell
      therapy due to their ease of isolation from bone marrow, their immunomodulatory
      and tissue repair capacities, their ability to differentiate into neuronal-like
      cells and to secrete a variety of growth factors and chemokines. In this study,
      we assessed the effects of a subpopulation of human MSCs, the marrow-isolated
      adult multilineage inducible (MIAMI) cells, combined with pharmacologically
      active microcarriers (PAMs) in a rat model of Parkinson's disease (PD). PAMs are
      biodegradable and non-cytotoxic poly(lactic-co-glycolic acid) microspheres,
      coated by a biomimetic surface and releasing a therapeutic protein, which acts on
      the cells conveyed on their surface and on their microenvironment. In this study,
      PAMs were coated with laminin and designed to release neurotrophin 3 (NT3), which
      stimulate the neuronal-like differentiation of MIAMI cells and promote neuronal
      survival. After adhesion of dopaminergic-induced (DI)-MIAMI cells to PAMs in
      vitro, the complexes were grafted in the partially dopaminergic-deafferented
      striatum of rats which led to a strong reduction of the amphetamine-induced
      rotational behavior together with the protection/repair of the nigrostriatal
      pathway. These effects were correlated with the increased survival of DI-MIAMI
      cells that secreted a wide range of growth factors and chemokines. Moreover, the
      observed increased expression of tyrosine hydroxylase by cells transplanted with
      PAMs may contribute to this functional recovery.

PMID- 21074845
TI  - The use of low molecular weight heparin-pluronic nanogels to impede liver
      fibrosis by inhibition the TGF-beta/Smad signaling pathway.
AB  - Low molecular weight heparin (LH) has been reported to have anti-fibrotic and
      anti-cancer effects. To enhance the efficacy and minimize adverse effects of LH,
      a low molecular weight heparin-pluronic nanogel (LHP) was synthesized by
      conjugating carboxylated pluronic F127 to LH. The LHP reduced anti-coagulant
      activity by about 33% of the innate activity. Liver fibrosis was induced by the
      injection of 1% dimethylnitrosamine (DMN) in rats, and LH or LHP (1000 IU/kg body
      weight) was treated once daily for 4 weeks. LHP administration prevented DMN
      mediated liver weight loss and decreased the values of aspartate transaminase,
      alanine transaminase, total bilirubin, and direct bilirubin. LHP markedly reduced
      the fibrotic area compared to LH. Also, LHP potently inhibited mRNA or protein
      expression of alpha-smooth muscle actin, collagen type I, matrix
      metalloproteinase-2, and tissue inhibitor of metalloproteinase-1 compared to LH,
      in DMN-induced liver fibrosis. In addition, LHP decreased the expression of
      transforming growth factor-beta(1) (TGF-beta(1)), p-Smad 2, and p-Smad 3, which
      are all important molecules of the TGF-beta/Smad signaling pathway. The results
      support an LHP shows anti-fibrotic effect in the liver via inhibition of the TGF
      beta/Smad pathway as well as by the elimination of the extracellular matrix.

PMID- 21074847
TI  - Integrin-targeted nanocomplexes for tumour specific delivery and therapy by
      systemic administration.
AB  - Nanoparticle formulations offer opportunities for tumour delivery of therapeutic
      reagents. The Receptor-Targeted Nanocomplex (RTN) formulation consists of a
      PEGylated, endosomally-cleavable lipid and an RGD integrin-targeting, endosomally
      cleavable peptide. Nancomplexes self-assemble on mixing with plasmid DNA to
      produce nanoparticles of about 100 nm. The environmentally-sensitive linkers
      promote intracellular disassembly and release of the DNA. RTNs carrying
      luciferase genes were administered intravenously to mice carrying subcutaneous
      neuroblastoma tumours. Luciferase expression was much higher in tumours than in
      liver, spleen and lungs while plasmid biodistribution studies supported the
      expression data. Transfection in tumours was enhanced two-fold by integrin
      targeting peptides compared to non-targeted nanocomplexes. RTNs containing the
      interleukin-2 (IL-2) and IL-12 genes were administered intravenously with seven
      doses at 48 h intervals and tumour growth monitored. Tumours from treated animals
      were approximately 75% smaller on day 11 compared with RTNs containing control
      plasmids with one third of treated mice surviving long-term. Extensive leukocyte
      infiltration, decreased vascularization and increased necrotic areas were
      observed in the tumours from IL2/IL12 treated animals. Splenocytes from re
      challenged mice displayed enhanced IL-2 production following Neuro-2A co-culture,
      which, combined with infiltration studies, suggested a cytotoxic T cell-mediated9
      tumour-rejection process. The integrin-targeted RTN formulation may have broader
      applications in the further development of cancer therapeutics.

PMID- 21074846
TI  - Combinatorial screening of osteoblast response to 3D calcium
      phosphate/poly(epsilon-caprolactone) scaffolds using gradients and arrays.
AB  - There is a need for combinatorial and high-throughput methods for screening cell
      biomaterial interactions to maximize tissue generation in scaffolds. Current
      methods employ a flat two-dimensional (2D) format even though three-dimensional
      (3D) scaffolds are more representative of the tissue environment in vivo and
      cells are responsive to topographical differences of 2D substrates and 3D
      scaffolds. Thus, combinatorial libraries of 3D porous scaffolds were developed
      and used to screen the effect of nano-amorphous calcium phosphate (nACP)
      particles on osteoblast response. Increasing nACP content in poly(epsilon
      caprolactone) (PCL) scaffolds promoted osteoblast adhesion and proliferation. The
      nACP-containing scaffolds released calcium and phosphate ions which are known to
      activate osteoblast function. Scaffold libraries were fabricated in two formats,
      gradients and arrays, and the magnitude of the effect of nACP on osteoblast
      proliferation was greater for arrays than gradients. The enhanced response in
      arrays can be explained by differences in cell culture designs, diffusional
      effects and differences in the ratio of "scaffold mass to culture medium". These
      results introduce a gradient library approach for screening large pore 3D
      scaffolds and demonstrate that inclusion of the nACP particles enhances
      osteoblast proliferation in 3D scaffolds. Further, comparison of gradients and
      arrays suggests that gradients were more sensitive for detecting effects of
      scaffold composition on cell adhesion (short time points, 1 day) whereas arrays
      were more sensitive at detecting effects on cell proliferation (longer time
      points, 14 day).

PMID- 21074848
TI  - Light induced drug delivery into cancer cells.
AB  - Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a
      broad variety of cargoes, including various nanoparticulate pharmaceutical
      carriers. However, the cationic nature of all CPP sequences, and thus lack of
      cell specificity, limits their in vivo use for drug delivery applications. Here,
      we have devised and tested a strategy for site-specific delivery of dyes and
      drugs into cancer cells by using polymers bearing a light activated caged CPP
      (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP
      penetratin ((52)RRMKWKK(58)) was masked with photo-cleavable groups to minimize
      non-specific adsorption and cellular uptake. Once illuminated by UV light, these
      protecting groups were cleaved, the positively charged CPP regained its activity
      and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug
      conjugates into cancer cells. We have found that a 10-min light illumination time
      was sufficient to enhance the penetration of the polymer-CPP conjugates bearing
      the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to
      promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in
      cell viability after 2 h. This report provides an example for tumor targeting by
      means of light activation of cell-penetrating peptides for intracellular drug
      delivery.

PMID- 21074849
TI  - Surface patterning using plasma-deposited fluorocarbon thin films for single-cell
      positioning and neural circuit arrangement.
AB  - Micropatterning glass substrates with a plasma-deposited fluoropolymer thin film
      was shown to be an efficient approach to manipulate cell positioning. The glass
      windows promoted cell adhesion, whereas the surrounding fluoropolymer displays a
      cell-repelling character. Herein, multiple micropatterned substrates were
      developed with pattern dimensions sufficient to host solely single-cells. These
      single-cell arrays would allow analysis of individual cell response to
      stimulation without interference from cell-cell interactions. Mouse myoblast
      C2C12 cells and cortical neurons from mice were examined, both for amenability to
      patterning, as well as success of cell adhesion and cell morphology. Both cell
      types were found to have optimal adherence and growth on the glass surface, while
      cell adhesion and function was inhibited on the fluoropolymer. The C2C12 cells
      conformed to the shape of the pattern, while maintaining a healthy structure.
      Moreover, the neuron cells followed the hexagonal grid patterns and formed
      circuits, wherein the complexity of the connections depended on incubation time.

PMID- 21074850
TI  - Periodontal pathogen Aggregatibacter actinomycetemcomitans LPS induces
      mitochondria-dependent-apoptosis in human placental trophoblasts.
AB  - OBJECTIVE: Increasing evidence suggests an association between periodontal
      disease and low birthweight (LBW); however the underlying molecular mechanisms
      are yet to be fully elucidated. In this study, we performed a microarray analysis
      to observe the human placental trophoblast-like BeWo cells response to
      lipopolysaccharide (LPS) from periodontopathogen Aggregatibacter
      actinomycetemcomitans (Aa), in order to investigate the molecular basis of
      mechanisms for periodontitis-associated LBW. In vivo pregnant rats were also used
      to confirm the in vitro results. STUDY DESIGN: The effects of Aa-LPS on cultured
      human placental trophoblast-like BeWo cells were studied using a DNA microarray,
      Ingenuity Pathway Analysis, real-time PCR and poly-caspase staining. The in vivo
      effects of Aa-LPS in pregnant rats were examined using TUNEL assays. RESULTS: In
      BeWo cells, Aa-LPS increased levels of cytochrome c, caspase 2, caspase 3,
      caspase 9 and BCL2-antagonist/killer 1 mRNA, decreased those of B-cell
      CLL/lymphoma 2, BCL2-like 1 and catalase mRNA and increased poly-caspase
      activity, all of which are consistent with activation of the mitochondria
      dependent apoptotic pathway. TUNEL assays confirmed the increased incidence of
      apoptosis in placentas of Aa-LPS-treated rats (p < 0.001). CONCLUSION: Aa-LPS
      induces apoptosis in human trophoblasts via the mitochondria-dependent pathway,
      and this effect may contribute to the pathogenesis of periodontitis-associated
      LBW.

PMID- 21074852
TI  - Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo
      remain sensitive to allogeneic immune effects.
AB  - Allogeneic hematopoietic stem cell transplantation is often performed for
      patients with acute lymphoblastic leukemia (ALL) whose disease has relapsed after
      chemotherapy treatment. However, graft versus leukemia (GVL) effects in ALL are
      generally weak and the mechanisms of this weakness are unknown. These studies
      tested the hypothesis that ALL cells that have survived conventional chemotherapy
      in vivo acquire relative resistance to the allogeneic GVL effect. C57BL/6 mice
      were injected with murine pre-B ALL lines driven by human mutations and then were
      treated with combination chemotherapy. ALL cells surviving therapy were analysed
      in vitro and in vivo for acquisition of resistance to chemotherapy, radiation,
      cytolytic T cells, NK cells, LAK cells and cytokines. In vivo drug treatment did
      lead to leukemia population with more rapid proliferation and also decreased
      sensitivity to vincristine, doxorubicin and radiation. However, drug treatment
      did not produce ALL populations that were less sensitive to GVL effects in vitro
      or in vivo.

PMID- 21074853
TI  - Oxidative stress induced by a commercial glyphosate formulation in a tolerant
      strain of Chlorella kessleri.
AB  - We studied the toxicity of a glyphosate formulation and provide evidence of
      metabolic alterations due to oxidative stress caused in a Chlorella kessleri
      tolerant strain by exposure to the herbicide. After 96 h of exposure to
      increasing concentrations of the herbicide (0-70 mg L(-1)) with alkylaryl
      polyglycol ether surfactant, growth was inhibited (EC50-96 h 55.62 mg L(-1)).
      Glyphosate increased protein and malondialdehyde content which was significantly
      higher than in the control at 50-70 mg L(-1). Superoxide dismutase and catalase
      activities and reduced glutathione levels increased in a concentration-dependant
      manner. Morphological studies showed increases in vacuolisation and in cell and
      sporangia sizes. The glyphosate formulation studied has a cytotoxic effect on C.
      kessleri through a mechanism that would involve the induction of oxidative
      stress. Upon glyphosate exposure, oxidative stress parameters such as SOD and CAT
      activities and MDA level could be more sensitive biomarkers than usually tested
      growth parameters in C. kessleri.

PMID- 21074854
TI  - Integrated assessment of mangrove sediments in the Camamu Bay (Bahia, Brazil).
AB  - Camamu Bay, an Environmentally Protected Area, may be affected by the pressures
      of tourism and oil exploration in the adjacent continental platform. The current
      quality of the mangrove sediments was evaluated by porewater bioassays using
      embryos of Crassostrea rhizophorae and by an analysis of benthic macrofauna and
      its relationships with organic compounds, trace metals and bioavailability.
      Porewater toxicity varied from low to moderate in the majority of the samples,
      and polychaetes dominated the benthos. The Grande Island sampling station
      (Station 1) presented more sandy sediments, differentiated macrobenthic
      assemblages and the highest metal concentrations in relation to other stations
      and guideline values, and it was the only station that indicated a possible
      bioavailability of metals. The origin of the metals (mainly barium) is most
      likely associated with the barite ore deposits located in the Grande and Pequena
      islands. These results may be useful for future assessment of the impact of oil
      exploration in the coastal region.

PMID- 21074851
TI  - Transcriptional mechanisms regulating Ca(2+) homeostasis.
AB  - Ca(2+) is a dynamic cellular secondary messenger which mediates a vast array of
      cellular responses. Control over these processes is achieved via an extensive
      combination of pumps and channels which regulate the concentration of Ca(2+)
      within not only the cytosol but also all intracellular compartments. Precisely
      how these pumps and channels are regulated is only partially understood, however,
      recent investigations have identified members of the Early Growth Response (EGR)
      family of zinc finger transcription factors as critical players in this process.
      The roles of several other transcription factors in control of Ca(2+) homeostasis
      have also been demonstrated, including Wilms Tumor Suppressor 1 (WT1), Nuclear
      Factor of Activated T cells (NFAT) and c-myc. In this review, we will discuss not
      only how these transcription factors regulate the expression of the major
      proteins involved in control of Ca(2+) homeostasis, but also how this
      transcriptional remodeling of Ca(2+) homeostasis affects Ca(2+) dynamics and
      cellular responses.

PMID- 21074855
TI  - Oxidative stress induced by gibberellic acid in bone of suckling rats.
AB  - The present study investigates the bone maturity of suckling rats whose mothers
      were treated with gibberellic acid (GA(3)). Female Wistar rats were divided into
      two groups: group I that served as controls and group II that received orally
      GA(3) (200 ppm) from the 14th day of pregnancy until day 14 after delivery. In
      the GA(3) group, an increase in body and femur weights as well as in femur length
      of pups was noted when compared to controls. Lipid peroxidation was demonstrated
      by high femur malondialdehyde levels, while superoxide dismutase, catalase,
      glutathione peroxidase activities, glutathione and vitamin C levels in femur
      decreased. GA(3) caused a decrease in calcium and phosphorus levels in bone. The
      calcium concentration in plasma increased and the phosphorus concentration
      decreased, while urinary levels of calcium decreased and those of phosphate
      increased. Moreover, plasma total tartrate-resistant acid phosphatase and total
      alkaline phosphatase increased. Bone disorders were confirmed by femur
      histological changes.

PMID- 21074856
TI  - Comparative antioxidative responses and proline metabolism in two wheat cultivars
      under short term lead stress.
AB  - This study investigated antioxidative response and proline metabolism in two
      wheat cultivars (Tritium aestivum Xihan 2 (Xihan) and Ningchun 4 (Ningchun))
      under Pb(NO(3))(2) stress. The constitutive H(2)O(2) scavenging enzyme activities
      and proline content in the leaves of drought-tolerant Xihan are higher than those
      in drought-sensitive Ningchun. Higher Pb concentration reduced chlorophyll
      content in both cultivars, but Ningchun was more sensitive to lead toxicity than
      Xihan. The higher activities of antioxidant enzyme and the significant proline
      accumulation provide protection for two wheat cultivars against lead toxicity,
      resulting in unaltered MDA content. Analysis of enzyme activities showed that the
      accumulation of proline induced by lead stress is due to the increases of OAT and
      GK activities in Xihan seedlings, and to the increase of GK activity in Ningchun
      leaves. Therefore, the different mechanism of proline metabolism was associated
      with increased proline levels in two wheat cultivars when exposed to lead stress.

PMID- 21074857
TI  - Non-cancer mortality in poultry slaughtering/processing plant workers belonging
      to a union pension fund.
AB  - BACKGROUND: The role of the biological environment in the occurrence of many
      chronic human diseases has been little studied. Humans are commonly exposed to
      transmissible agents that infect and cause a wide variety of subacute and chronic
      diseases in chickens and turkeys. The objective of this study is to investigate
      whether these agents cause similar diseases in humans, by studying workers in
      poultry slaughtering and processing plants who have one of the highest human
      exposures to these agents. METHODS: Mortality in poultry workers was compared
      with that in the United States general population through the estimation of
      standardized mortality ratios. RESULTS: Excess mortality from infectious and
      parasitic diseases was observed in the poultry workers. In addition, excess
      occurrences of deaths involving several sites of the cardiovascular,
      neurological, endocrine, gastrointestinal and reproductive systems, were
      observed, although the numbers involved were few in some instances. CONCLUSION:
      The results indicate that poultry workers are at increased risk of dying from
      certain causes of death, including infections. This is consistent with other
      reports. Although it is possible that occupational exposure to transmissible
      agents present in poultry may be one of the causes of the excess occurrence of
      some of these diseases, other factors that were not considered because of the
      nature of the study design, could be equally important. Also, the small number of
      deaths involved in some instances calls for caution in interpreting the results.
      However, the study is important, as it has succeeded in newly identified areas
      that need further research, and which may have implications not only for workers,
      but also for the general population.

PMID- 21074859
TI  - Affective bias in internal attention shifting among depressed youth.
AB  - The present study compared the performance of depressed youths and healthy
      controls on a modified mental counting task. The mental counting task was
      designed to capture processes associated with shifting the internal focus of
      attention by requiring participants to count random runs of words appearing on a
      computer screen. The words belonged to two different categories, and participants
      were required to maintain a count of the number of words in each category.
      Participants' reaction time to successfully update their counts and call for
      subsequent stimuli was measured. In particular, two versions of the modified
      counting task were developed: one incorporating neutral words and the other
      affective words. Overall, our findings in reaction time analysis suggest that
      depressed patients exhibited greater difficulty switching their internal focus of
      attention in the affective task when compared to healthy controls, even when
      controlling for their rate of accuracy. However, there was no significant
      difference between the groups during the neutral task. Results support the
      hypothesis that depression is related to impaired internal attention shifting
      when processing affective material.

PMID- 21074858
TI  - High-resolution imaging of the photoreceptor layer in epiretinal membrane using
      adaptive optics scanning laser ophthalmoscopy.
AB  - OBJECTIVE: To compare, in eyes with an idiopathic epiretinal membrane (ERM),
      photoreceptor cell structural abnormalities identified on high-resolution images
      obtained by adaptive optics scanning laser ophthalmoscopy (AO-SLO) with the
      severity of metamorphopsia and anatomic findings on spectral-domain optical
      coherence tomography (SD-OCT). DESIGN: Observational case series. PARTICIPANTS:
      Twenty-five eyes of 24 patients with idiopathic ERM and 20 normal eyes of 20
      volunteer subjects. METHODS: All participants underwent a full ophthalmologic
      examination, SD-OCT, and imaging with an original prototype AO-SLO system that
      incorporated liquid crystal-on-silicon technology. In eyes with ERM, M-CHARTS
      results were used to quantify metamorphopsia. MAIN OUTCOME MEASURES: Cone mosaic
      patterns on AO-SLO images and metamorphopsia severity. RESULTS: In normal eyes,
      AO-SLO images showed a regular photoreceptor mosaic pattern. In 24 (96%) of 25
      eyes with ERM, "microfolds" (multiple thin, straight, hyporeflective lines in the
      photoreceptor layer) were identified on AO-SLO images; microfolds were not seen
      in normal eyes. Individual microfolds were approximately 5 to 20 MUm wide, which
      is narrower than retinal folds seen in fundus photographs (>50 MUm). Amsler
      charts revealed metamorphopsia around the fixation point in 12 of 13 eyes with
      microfolds in the fovea on AO-SLO but in none of 5 eyes without microfolds in the
      fovea (P < 0.001). Compared with eyes without foveal microfolds, eyes with foveal
      microfolds had more severe metamorphopsia (M-CHARTS distortion) in both
      horizontal and vertical lines (P < 0.001 for both) and greater average foveal
      thickness detected by SD-OCT (P=0.010). Voronoi analysis revealed that smaller
      numbers of cones in eyes with ERM had 6 neighbors, compared with normal eyes (P <
      0.001). In eyes with ERM, average foveal thickness measured by SD-OCT correlated
      with visual acuity (P=0.001) and metamorphopsia scores, both horizontal (P=0.002)
      and vertical (P < 0.001), but visual acuity, metamorphopsia scores, and average
      foveal thickness were not related to SD-OCT findings of disruption in the
      photoreceptor inner and outer segment junction. CONCLUSIONS: Adaptive optics
      scanning laser ophthalmoscopy images in eyes with ERM showed abnormal cone mosaic
      patterns, described as microfolds in the foveal photoreceptor layer. The presence
      of microfolds was associated with metamorphopsia, suggesting that microfolds may
      be involved in the formation of metamorphopsia.

PMID- 21074860
TI  - How do socio-demographic and clinical factors interact with adherence attitude
      profiles in schizophrenia? A cluster-analytical approach.
AB  - Knowledge regarding socio-demographic and clinical risk factors of medication
      nonadherence does not always help in addressing adherence in individual patients.
      Classifying patients according to subjective adherence influencing factors may
      aid practitioners in choosing adequate strategies for improving medication
      adherence. A total of 171 outpatients with schizophrenia and schizoaffective
      disorder were classified according to factors influencing their medication
      adherence assessed using the Rating of Medication Influences Scale. Additionally,
      psychotic symptoms, depression, and insight, also known to influence
      pharmacological treatment motivation, were assessed. A cluster analysis yielded 3
      groups that were distinguished both by the relative ranking of adherence
      influences and by specific associations with risk factors of nonadherence. For
      the "Interpersonal, Future-oriented Group" (n=59, 35% of the sample),
      interpersonal factors (positive therapeutic relationship, positive attitudes of
      significant others towards medication), immediate positive consequences of the
      medication intake (daily benefits, no perceived pressure to take medication), and
      avoiding future negative consequences of non-compliance, such as relapse and re
      hospitalization, were essential for adherence. The "Autonomous, Future-oriented
      Group" (n=69, 40% of the sample) appraised interpersonal factors as being less
      important as compared to the other groups. This group exhibited significantly
      fewer depressive symptoms than the first group and had significantly more stable
      partnerships as compared to the other groups. The "Autonomous, Present-oriented
      Group" (n=43, 25% of the sample) was mainly motivated by immediate positive
      consequences and displayed higher levels of cognitive disorganization and
      negative symptoms than the second group, as well as the lowest level of insight
      of all groups. Treatment strategies addressing adherence enhancement in
      schizophrenia may profit by considering both the patient's subjective adherence
      attitude profile as well as the specific pattern of risk factors for nonadherence
      including depression, lack of insight, negative syndrome, cognitive
      disorganization and socio-demographic factors, which are differentially
      associated with each adherence attitude profile.

PMID- 21074861
TI  - Expressed gene sequences of two variants of sheep interleukin-25.
AB  - This report describes the cloning and characterization of sheep interleukin-25
      (IL25) expressed gene sequences and shows that, like humans, sheep express two
      transcript variants of IL25. Transcript variant 1 (IL25v1) has a 510 bp open
      reading frame encoding a 169 amino acid polypeptide with a calculated M(r)
      19,200. The 498 bp IL25v2 encodes a 165 amino acid polypeptide with a calculated
      M(r) 18,710; both with an isoelectric point equal to 8.0307. The additional 12 bp
      of IL-25 isoform 1 are at the 5' end and encode an MYQA peptide, otherwise their
      sequences are identical. Phylogenetic analysis shows that both sheep IL-25
      isoforms are most closely related to cattle and pig IL-25.

PMID- 21074862
TI  - Clinical and immunological differences between early and late-onset myasthenia
      gravis in Japan.
AB  - Immunological characteristics of myasthenia gravis (MG) with late-onset have not
      been fully elucidated. We examined several autoantibodies and HLA-DRB1 genotyping
      in 260 Japanese MG patients. Sixty-two MG patients had thymoma. The others were
      divided into early-onset and late-onset groups separated by an age of 50 years.
      The ocular form was more frequent in late-onset compared to early-onset group.
      Seropositivity of anti-muscle-specific tyrosine kinase antibody was 2-3% in
      acetylcholine receptor-seronegative patients. HLA-DRB1 genotyping failed to
      detect statistical differences in specific alleles between each group and healthy
      controls. The immunological profiles in late-onset MG were different from early
      onset in Japan.

PMID- 21074863
TI  - Staphylococcus aureus sinus infections in children.
AB  - OBJECTIVE: Staphylococcus aureus can cause sinusitis in children. The predominant
      MRSA clone in the United States, USA300, has been associated with skin and soft
      tissue as well as invasive diseases. USA300 has increased among CA methicillin
      susceptible S. aureus (CA-MSSA) isolates. We describe the clinical
      characteristics of pediatric patients with S. aureus cultured from sinus
      specimens, treated at Texas Children's Hospital (TCH), and characterized their
      isolates by molecular methods. METHODS: This was a retrospective study of
      children with endoscopic sinus surgery (ESS) cultures positive for S. aureus
      between 01/2005 and 12/2008 at TCH. Medical records were reviewed and associated
      S. aureus isolates were characterized by pulsed field gel electrophoresis (PFGE).
      Data were analyzed by Mann-Whitney U, Chi-square, Fisher's exact test, and Chi
      square for trend. RESULTS: We identified 56 patients with S. aureus sinus
      infections; 12 (21%) were MRSA. Seven of 12 (58%) MRSA vs. 5/44 (11%) MSSA were
      USA300 (p<0.01). All MRSA isolates were non-susceptible to erythromycin compared
      to 30% of MSSA (p<0.01); 75% of the USA300 strains were non-susceptible to
      erythromycin compared to 36% of the non-USA300 strains (p<0.04). Co-pathogens
      were isolated from 77% (43/56) of the patient specimens. Both MRSA and USA300
      isolates were associated with Haemophilus influenzae co-isolation (p<0.05).
      Patients with USA300 strains were significantly younger (p=0.02) and more likely
      to experience snoring as a symptom associated with their sinusitis (p=0.03) than
      those infected with non-USA300 strains. Children with MRSA (4/12) tended to have
      a greater recurrence rate than children with MSSA isolates (5/44) (p=0.09). No
      significant differences were observed between groups for fever or complications
      such as neck cellulitis, nasal abscess, meningitis, subdural empyema, and orbital
      cellulitis. CONCLUSION: MSSA was more commonly isolated than MRSA from sinus
      cultures of children who underwent ESS at TCH. The majority of ESS cultures
      positive for S. aureus, were mixed with other respiratory pathogens, principally
      H. influenzae. USA300 was the major clone among the MRSA sinusitis isolates, but
      was not associated with more complications than other S. aureus isolates.

PMID- 21074864
TI  - An initial overestimation of sensorineural hearing loss in NICU infants after
      failure on neonatal hearing screening.
AB  - OBJECTIVE: Infants admitted to neonatal intensive care units have a higher
      incidence of significant congenital hearing loss. We classified audiologic
      diagnoses and follow-up in infants who had been admitted to our neonatal
      intensive care unit. METHODS: We included all infants admitted to the neonatal
      intensive care unit at Sophia Children's Hospital between 2004 and 2009 who had
      been referred for auditory brainstem response measurement after failing neonatal
      hearing screening with automated auditory brainstem response. We retrospectively
      analyzed the results of auditory brainstem response measurement. RESULTS: Between
      2004 and 2009 3316 infants admitted to our neonatal intensive care unit had
      neonatal hearing screening. 103 infants failed neonatal hearing screening: 46
      girls and 57 boys. After first auditory brainstem response measurement we found
      18% had normal hearing or a minimal hearing loss. The remainder had a type of
      hearing loss, distributed as follows: 15% conductive, 32% symmetric
      sensorineural, 14% asymmetric sensorineural, and 21% absent auditory brainstem
      responses. Repeated auditory brainstem response measurement showed a shift in
      hearing outcome. The main difference was an improvement from symmetric
      sensorineural hearing loss to normal hearing. However, in a small percentage of
      children, the hearing deteriorated. CONCLUSIONS: As many as 58% of infants in
      this high-risk population who failed the neonatal hearing screening were
      diagnosed with sensorineural hearing loss or absent auditory brainstem responses.
      An initial overestimation of sensorineural hearing loss of about 10% was seen at
      first auditory brainstem response measurement. This may be partially explained by
      a conductive component that has resolved. Finally, in a small percentage of
      children the hearing deteriorated.

PMID- 21074865
TI  - Balance ability of 7 and 10 year old children in the population: results from a
      large UK birth cohort study.
AB  - OBJECTIVE: The literature contains many reports of balance function in children,
      but these are often on atypical samples taken from hospital-based clinics and may
      not be generalisable to the population as a whole. The purpose of the present
      study is to describe balance test results from a large UK-based birth cohort
      study. METHODS: Data from the Avon Longitudinal Study of Parents and Children
      (ALSPAC) were analysed. A total of 5402 children completed the heel-to-toe
      walking test at age 7 years. At age 10 years, 6915 children underwent clinical
      tests of balance including beam-walking, standing heel-to-toe on a beam and
      standing on one leg. A proportion of the children returned to the clinic for
      retesting within 3 months allowing test-retest agreement to be measured. RESULTS:
      Frequency distributions for each of the balance tests are given. Correlations
      between measures of dynamic balance at ages 7 and 10 years were weak. The static
      balance of 10 year old children was found to be poorer with eyes closed than with
      eyes open, and poorer in boys than in girls for all measures. Balance on one leg
      was poorer than heel-to-toe balance on a beam. A significant learning effect was
      found when first and second attempts of the tests were compared. Measures of
      static and dynamic balance appeared independent. Consistent with previous reports
      in the literature, test-retest reliability was found to be low. CONCLUSIONS: This
      study provides information about the balance ability of children aged 7 and 10
      years and provides clinicians with reference data for balance tests commonly used
      in the paediatric clinic.

PMID- 21074866
TI  - Radiofrequency ablation as a novel treatment for lingual thyroid.

PMID- 21074867
TI  - Multifocal septic arthritis with Group A Streptococcus secondary to nasal septal
      abscess.
AB  - This report describes a previously healthy adolescent male who developed a nasal
      septal abscess following trauma and subsequent multifocal arthritis with Group A
      Streptococcus requiring surgery and prolonged antibiotics. This sequence of
      events has not been previously described in the literature. This report
      highlights the importance of early recognition and treatment of traumatic nasal
      septal hematoma to reduce the risk of suppurative complications.

PMID- 21074868
TI  - Landau-Kleffner syndrome: a rare auditory processing disorder series of cases and
      review of the literature.
AB  - OBJECTIVE: To describe the clinical presentation and treatment of 3 children with
      an Auditory Processing Disorder with an identifiable neurological cause: Landau
      Kleffner syndrome. This classical syndrome is well recognized in pediatric
      neurology but the diagnosis is less well known to Pediatric Otolaryngology,
      Speech Language Pathology and Audiology services. METHODS: Retrospective chart
      review of three patients with Landau-Kleffner syndrome. RESULTS: In all cases,
      pharmacological intervention led to clinical and electroencephalographic
      improvement, but all patients had long-term difficulty with understanding sounds
      in a noisy environment. Magnetic Resonance Imaging (MRI) of the brain was normal
      in all three patients. Their language disturbance improved over time. Speech
      language intervention was helpful in addressing communication difficulties
      arising from the auditory processing/receptive and expressive language disorder.
      CONCLUSION: A multidisciplinary assessment is the key for early diagnosis,
      treatment and follow-up in patients with this syndrome.

PMID- 21074869
TI  - Environmentally induced oxidative stress in aquatic animals.
AB  - Reactive oxygen species (ROS) are an unenviable part of aerobic life. Their
      steady-state concentration is a balance between production and elimination
      providing certain steady-state ROS level. The dynamic equilibrium can be
      disturbed leading to enhanced ROS level and damage to cellular constituents which
      is called "oxidative stress". This review describes the general processes
      responsible for ROS generation in aquatic animals and critically analyses used
      markers for identification of oxidative stress. Changes in temperature, oxygen
      levels and salinity can cause the stress in natural and artificial conditions via
      induction of disbalance between ROS production and elimination. Human borne
      pollutants can also enhance ROS level in hydrobionts. The role of transition
      metal ions, such as copper, chromium, mercury and arsenic, and pesticides, namely
      insecticides, herbicides, and fungicides along with oil products in induction of
      oxidative stress is highlighted. Last years the research in biology of free
      radicals was refocused from only descriptive works to molecular mechanisms with
      particular interest to ones enhancing tolerance. The function of some
      transcription regulators (Keap1-Nrf2 and HIF-1alpha) in coordination of
      organisms' response to oxidative stress is discussed. The future directions in
      the field are related with more accurate description of oxidative stress, the
      identification of its general characteristics and mechanisms responsible for
      adaptation to the stress have been also discussed. The last part marks some
      perspectives in the study of oxidative stress in hydrobionts, which, in addition
      to classic use, became more and more popular to address general biological
      questions such as development, aging and pathologies.

PMID- 21074870
TI  - C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as inflammation
      markers in elderly patients with stable chronic obstructive pulmonary disease
      (COPD).
AB  - Erythrocyte sedimentation rate (ESR) might represent a less expensive alternative
      to C-reactive protein (CRP) as a marker of systemic inflammation in stable
      chronic obstructive pulmonary disease (COPD). We tried to verify this hypothesis
      in 223 consecutive outpatients aged 65 years or more with stable COPD enrolled in
      a multicenter observational study. Patients were grouped according to
      normal/increased ESR/CRP values and groups were compared with regard to clinical
      and laboratory characteristics. Correlations between CRP, ESR and selected
      variables of interest were assessed by Spearman's zeta-test and multivariate
      linear regression analysis. CRP was weakly and inversely correlated with the
      forced expiratory volume in the first second (FEV1%) (Spearman's zeta = -0.15; p
      < 0.027), while ESR was not (Spearman's zeta = -0.05; p = 0.411). The highest
      prevalence of anemia and hypoalbuminemia and the lowest FEV1% were recorded in
      high ESR-high CRP group. For anemia B = 14.180 +/- 3.521 (+/- S.E.M.); p = 0.001
      and hypoalbuminemia B = 10.241 +/- 3.790; p = 0.007 qualified as significant
      independent correlates of ESR values, while only FEV1 remained significantly
      associated with CRP values (B = -0.570 +/- 0.258; p = 0.028). In conclusion, CRP,
      but not ESR, shows a weak correlation with COPD severity, while anemia and
      hypoalbuminemia are main correlates of high ESR. Neither ESR, nor CRP qualify as
      reliable markers of COPD severity and seem to reflect the effects of different
      determinants.

PMID- 21074871
TI  - Homocysteine as a new risk factor for cardiovascular events in heart failure.

PMID- 21074872
TI  - Is small heart syndrome a "heart" disease or low output syndrome?

PMID- 21074873
TI  - The effect of Paragraph IV decisions and generic entry before patent expiration
      on brand pharmaceutical firms.
AB  - This purpose of this paper is to investigate the impact of Paragraph IV patent
      infringement decisions on brand drug pharmaceutical firms. Paragraph IV decisions
      determine whether a generic firm can enter before the period of exclusivity ends.
      I construct a novel dataset of all Paragraph IV decisions and find that they
      disproportionately involve the highest revenue drugs, significant periods of
      patent protection, and a non-trivial portion of all brand drugs facing generic
      entry. I also estimate the impact of Paragraph IV decisions on brand firm
      profitability and find they have large value consequences.

PMID- 21074874
TI  - The role of education in complex health decisions: evidence from cancer
      screening.
AB  - This paper uses data on real and perceived cancer risks and cancer screening
      behavior to test the allocative efficiency theory. Specifically, it explores
      whether the educated make better-informed health decisions. I propose that (1)
      when educated individuals are better informed, they are more likely to
      incorporate variation in risk factors when they report their personal cancer
      risk, and (2) as risk varies, the better educated will react more strongly by
      adopting preventive behaviors such as cancer screening. The results support for
      both predictions. Further, using data on attitudes toward breast health, I
      explore a possible mechanism: educated women are more receptive to scientific
      evidence and hold fewer nonscientific beliefs.

PMID- 21074875
TI  - Patterns of relapse following definitive treatment of head and neck squamous cell
      cancer by intensity modulated radiotherapy and weekly cisplatin.
AB  - Eighty-three patients with oropharyngeal, hypopharyngeal or laryngeal cancer were
      treated with concomitant cisplatin 40 mg/m(2) once a week during the radiotherapy
      and IMRT up to a total dose of 70 Gy. The 2-year rate of local control, overall
      survival and disease specific survival were 84%, 82% and 89%, respectively. The
      corresponding 5-year Kaplan-Meier estimates were 79%, 69% and 76%.

PMID- 21074877
TI  - Long term survival of an atlas osteosarcoma treated by surgery, chemotherapy and
      robotic stereotactic radiotherapy: a case report.

PMID- 21074876
TI  - Durable palliation of breast cancer chest wall recurrence with radiation therapy,
      hyperthermia, and chemotherapy.
AB  - BACKGROUND AND PURPOSE: Chest wall recurrences of breast cancer are a therapeutic
      challenge and durable local control is difficult to achieve. Our objective was to
      determine the local progression free survival (LPFS) and toxicity of
      thermochemoradiotherapy (ThChRT) for chest wall recurrence. METHODS: Twenty-seven
      patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up
      this retrospective series. All received concurrent superficial hyperthermia twice
      weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2,
      and paclitaxel in 4), and radiation (median 45 Gy). Patients were followed up
      every 1.5-3 months and responses were graded with RECIST criteria and toxicities
      with the NCI CTC v4.0. RESULTS: Twenty-three (85%) patients were previously
      irradiated (median 60.4 Gy) and 22 (81%) patients received prior chemotherapy.
      Median follow-up was 11 months. Complete response (CR) was achieved in 16/20
      (80%) of patients with follow-up data, and 1 year LPFS was 76%. Overall survival
      was 23 months for patients with CR, and 5.4 months in patients achieving a
      partial response (PR) (p=0.01). Twenty-two patients experienced acute grade 1/2
      treatment related toxicities, primarily moist desquamation. Two patients
      experienced 3rd degree burns; all resolved with conservative measures.
      CONCLUSIONS: ThChRT offers durable palliation and prolonged LPFS with tolerable
      acute toxicity, especially if CR is achieved.

PMID- 21074878
TI  - Stereotactic radiotherapy for peripheral lung tumors: a comparison of volumetric
      modulated arc therapy with 3 other delivery techniques.
AB  - PURPOSE: Volumetric modulated arc therapy (RapidArc) allows for fast delivery of
      stereotactic body radiotherapy (SBRT) delivery in stage I lung tumors. We
      compared dose distributions and delivery times between RapidArc and common
      delivery techniques in small tumors. METHODS: In 18 patients who completed
      RapidArc SBRT for tumors measuring <70 cm(3), new treatment plans were generated
      using non-coplanar 3D conformal fields (conf-SBRT) and dynamic conformal arc
      radiotherapy (DCA). For 9 patients with tumors adjacent to the chest wall, co
      planar intensity-modulated radiotherapy (IMRT) plans were also generated. PTV
      dose coverage, organs at risk (OAR) doses and treatment delivery times were
      assessed. RESULTS: RapidArc plans achieved a superior conformity index (CI) and
      lower V(45 Gy) to chest wall (p<0.05) compared to all other techniques. RapidArc
      led to a small increase in V(5 Gy) to contralateral lung compared to conf-SBRT
      (4.4+/-4% versus 1.2+/-1.8%, p=0.011). For other OAR, RapidArc and conf-SBRT
      plans were comparable, and both were superior to DCA plans. Delivery of a 7.5 Gy
      fraction required 3.9 min (RapidArc), 11.6 min (conf-SBRT), and 12 min (IMRT).
      CONCLUSIONS: In stage I lung tumors measuring <70 cm(3), RapidArc plans achieved
      both the highest dose conformity and shortest delivery times.

PMID- 21074879
TI  - On autoradiographic studies comparing the distributions of 18F- and 14C-labeled
      compounds in tumor tissue specimens.

PMID- 21074880
TI  - Details of recurrence sites after elective nodal irradiation (ENI) using 3D
      conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic
      esophageal squamous cell carcinoma--a retrospective analysis.
AB  - PURPOSE: To describe patterns of recurrence of elective nodal irradiation (ENI)
      in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell
      carcinoma (SqCC) using 3D-conformal radiotherapy. METHODS AND MATERIALS: One
      hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal
      SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in
      our institution were recruited from our database. Definitive CRT consisted of two
      cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation
      therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was
      delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume.
      RESULTS: All 126 patients were included in this analysis, and their tumors were
      staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30.
      The mean follow-up period for the 63 surviving patients was 28.3 (+/-22.8)
      months. Eighty-seven patients (69%) achieved complete response (CR) without any
      residual tumor at least once after completion of CRT. After achieving CR, each of
      40 patients experienced failures (local=20 and distant=20) and no patient
      experienced elective nodal failure without having any other site of recurrence.
      The upper thoracic esophageal carcinoma showed significantly more (34%) relapses
      at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2
      year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2
      year and 3-year disease-free survival was 46%, 38% and 33%, respectively.
      CONCLUSIONS: In CRT for esophageal SqCC, ENI was effective for preventing
      regional nodal failure. The upper thoracic esophageal carcinomas had
      significantly more local recurrences than the middle or lower thoracic sites.

PMID- 21074881
TI  - 3D CT-based high-dose-rate brachytherapy for cervical cancer: clinical impact on
      late rectal bleeding and local control.
AB  - BACKGROUND AND PURPOSE: To identify the impact of 3D CT-based high-dose-rate
      intracavitary radiotherapy (ICR) on late rectal bleeding (LRB) and local control
      (LC) in patients with cervical cancer. MATERIAL AND METHODS: The outcomes of 97
      consecutive patients treated with 3D CT-based ICR (3D-ICR) were compared with
      those of 133 consecutive historical patients with conventional 2D brachytherapy
      planning (2D-ICR). The median follow-up periods were 41 and 56 months for the 3D
      and 2D groups, respectively. RESULTS: The overall rectal bleeding rate was
      similar between the groups (42% for 3D-ICR vs. 44% for 2D-ICR); however, the
      incidence of severe LRB was higher in the 2D-ICR group than in the 3D-ICR group
      (13% vs. 2%, respectively; p=0.02). In multivariate analysis, the factors
      associated with severe LRB were tumor >4 cm (12% vs. 3%) and 2D-ICR (10% vs. 2%).
      The LC rates were 97% and 91% for 3D-ICR and 2D-ICR, respectively (p=0.14); the
      progression-free survival rate was 80% for both groups. A significant difference
      in the LC rates between the two groups was observed in patients with larger tumor
      sizes with the tumor diameter of over 4 cm (98% vs. 81% by 3D-ICR vs. 2D-ICR,
      respectively; p=0.02). CONCLUSIONS: The implementation of 3D-ICR in radiotherapy
      for cervical cancer can reduce the incidence of severe LRB and may improve the LC
      rate.

PMID- 21074882
TI  - Gradient-based delineation of the primary GTV on FDG-PET in non-small cell lung
      cancer: a comparison with threshold-based approaches, CT and surgical specimens.
AB  - PURPOSE: The aim of this study was to validate a gradient-based segmentation
      method for GTV delineation on FDG-PET in NSCLC through surgical specimen, in
      comparison with threshold-based approaches and CT. MATERIALS AND METHODS: Ten
      patients with stage I-II NSCLC were prospectively enrolled. Before lobectomy, all
      patients underwent contrast enhanced CT and gated FDG-PET. Next, the surgical
      specimen was removed, inflated with gelatin, frozen and sliced. The digitized
      slices were used to reconstruct the 3D macroscopic specimen. GTVs were manually
      delineated on the macroscopic specimen and on CT images. GTVs were automatically
      segmented on PET images using a gradient-based method, a source to background
      ratio method and fixed threshold values at 40% and 50% of SUV(max). All images
      were finally registered. Analyses of raw volumes and logarithmic differences
      between GTVs and GTV(macro) were performed on all patients and on a subgroup
      excluding the poorly defined tumors. A matching analysis between the different
      GTVs was also conducted using Dice's similarity index. RESULTS: Considering all
      patients, both lung and mediastinal windowed CT overestimated the macroscopy,
      while FDG-PET provided closer values. Among various PET segmentation methods, the
      gradient-based technique best estimated the true tumor volume. When analysis was
      restricted to well defined tumors without lung fibrosis or atelectasis, the
      mediastinal windowed CT accurately assessed the macroscopic specimen. Finally,
      the matching analysis did not reveal significant difference between the different
      imaging modalities. CONCLUSIONS: FDG-PET improved the GTV definition in NSCLC
      including when the primary tumor was surrounded by modifications of the lung
      parenchyma. In this context, the gradient-based method outperformed the threshold
      based ones in terms of accuracy and robustness. In other cases, the conventional
      mediastinal windowed CT remained appropriate.

PMID- 21074883
TI  - Dosimetric effect of target expansion and setup uncertainty during radiation
      therapy in pediatric craniopharyngioma.
AB  - PURPOSE: Investigate the effect of tumor change and setup uncertainties on target
      coverage for pediatric craniopharyngioma during RT. METHODS AND MATERIALS:
      Fifteen pediatric patients with craniopharyngioma (mean 5.1 years) were included
      in this study. MRI was performed before and a median of six times during RT to
      monitor changes in the tumor volume. IMRT plans were created and compared to the
      CRT plan used for treatment. The role of adaptive therapy based on GTV changes
      was investigated. Dosimetric effects of interfraction and intrafraction motion
      were examined. RESULTS: The mean of the maximal change in the GTV was 28.5% [
      20.7% to 82.0%]. For the standard margin IMRT plans, the mean D(95) of the base
      plan on the base target was 53.6 Gy [53.1-54.1]. The mean D(95) of the base plans
      on the adaptive targets was 52.1 Gy [47.9-54.1]. The D(95) for the adaptive plan
      on the adaptive target was 53.8 Gy [53.4-54.3]. A linear regression equation of
      y=-0.12x , r(2)=0.70, was found for the percent change in D(95) of the PTV (y)
      vs. the percent change in the GTV (x). Inter and intrafraction motion did not
      affect the target coverage for standard and reduced margin plans. CONCLUSIONS:
      The GTV of pediatric craniopharyngioma patients change size during therapy and
      adaptive planning is critical for conformal plans; therefore early and regular
      surveillance imaging is required.

PMID- 21074884
TI  - A practical approach to assess clinical planning tradeoffs in the design of
      individualized IMRT treatment plans.
AB  - BACKGROUND AND PURPOSE: To investigate the tradeoffs between organ at risk
      sparing and tumour coverage for IMRT treatment of lung tumours, and to develop a
      tool for clinical use to graphically represent these tradeoffs. MATERIAL AND
      METHODS: For 5 patients with inoperable non-small cell lung cancer (NSCLC)
      different IMRT plans were generated using a standard TPS. The plans were
      automatically generated for a range of IMRT settings (weights and dose levels of
      the objective functions) and were systematically evaluated, focusing on the
      tradeoffs between organ at risk (OAR) dose and target coverage. A method to
      analyze and visualize planning tradeoffs was developed and evaluated. RESULTS:
      Lung and oesophagus were identified as the critical organs at risk for NSCLC, the
      sparing of which strongly influences PTV coverage. Systematically analyzing the
      tradeoffs between these organs revealed that the sparing of these organs was
      approximately linearly related to PTV coverage parameters. Using this property, a
      tool was developed to graphically present the tradeoffs between the sparing of
      these organs at risk and the PTV coverage. The tool is an effective method to
      visualize the tradeoffs. CONCLUSIONS: A tool was developed to assist IMRT plan
      design and selection. The clear presentation of the tradeoffs between OAR dose
      and coverage facilitates the optimization process and offers additional
      information to the clinician for a patient specific choice of the optimal IMRT
      plan.

PMID- 21074885
TI  - Prevalence and characterization of antimicrobial resistance of foodborne Listeria
      monocytogenes isolates in Hebei province of Northern China, 2005-2007.
AB  - A total of 2177 food samples collected from nine cities in northern China during
      2005 to 2007 were screened for the presence of Listeria monocytogenes. All L.
      monocytogenes isolates were subjected to serotyping, antimicrobial
      susceptibility, pulsed-field gel electrophoresis (PFGE), as well as PCR screening
      to identify genes responsible for tetracycline resistance [tet(L), tet(M),
      tet(K), tet(S) and tet(B)], transposon Tn916, and class 1 integron. Contamination
      with L. monocytogenes was detected in 4.13% (90/2177) of the total samples
      representing various food products. The pathogen was mainly isolated from frozen
      food made of wheat flour or rice products (26/252, 10.32%) and raw meat products
      (46/733, 6.28%). Besides, 3.31% (10/302) of cooked meat, 1.17% (4/343) of
      seafood, 0.98% (2/204) of non-fermented bean products and 0.62% (2/323) of
      vegetables samples were contaminated by this bacterium. The L. monocytogenes
      isolates belonged to five serotypes (1/2a, 1/2b, 1/2c, 4b, and 3a), with serotype
      1/2a being dominant (48.88%). Antimicrobial resistance was most frequently
      observed for ciprofloxacin (17.8%), tetracycline (15.6%) and streptomycin
      (12.2%). Overall, resistance was observed against 14 out of 18 antimicrobials
      tested while multiple resistances occurred among 18.9% (17/90) isolates.
      Interestingly, two isolates were resistant to more than five antimicrobials.
      Among 14 tetracycline-resistant isolates, 13 carried tet(M) gene including nine
      possessing Tn916, and one harbored tet(S) gene. PFGE analysis revealed genetic
      heterogeneity among individual serotypes as well as scattered occurrence of some
      genotypes without any clear-cut correlation to source or food type. The
      widespread distribution of epidemiologically important serotypes (1/2a, 1/2b and
      4b) of L. monocytogenes, and their resistance to commonly used antibiotics
      indicate a potential public health risk. Our data also indicate that L.
      monocytogenes could act as a reservoir of mobile tet genes along the food chain.

PMID- 21074886
TI  - Sub-lethal heat treatment affects the tolerance of Cronobacter sakazakii BCRC
      13988 to various organic acids, simulated gastric juice and bile solution.
AB  - Cronobacter spp., formerly Enterobacter sakazakii, are considered emerging
      opportunistic pathogens and the etiological agent of life-threatening bacterial
      infections in infants. In the present study, C. sakazakii BCRC 13988 was first
      subjected to sub-lethal heat treatment at 47 degrees C for 15min. Survival rates
      of the heat-shocked and non-shocked C. sakazakii cells in phosphate buffer
      solution (PBS, pH 4.0) containing organic acids (e.g. acetic, propionic, citric,
      lactic or tartaric acid), simulated gastric juice (pH 2.0-4.0), and bile solution
      (0.5 and 2.0%) were examined. Results revealed that sub-lethal heat treatment
      enhanced the test organism's tolerance to organic acids, although the extent of
      increased acid tolerance varied with the organic acid examined. Compared with the
      control cells, heat-shocked C. sakazakii cells after 120-min of exposure,
      exhibited the largest increase in tolerance in the lactic acid-containing PBS.
      Furthermore, although heat shock did not affect the behavior of C. sakazakii in
      bile solution, it increased the test organism's survival when exposed to
      simulated gastric juice with a pH of 3.0-4.0.

PMID- 21074888
TI  - Evolutionary dynamics of transposable elements in a small RNA world.
AB  - Transposable elements (TEs) are selfish elements that cause harmful mutations,
      contribute to the structure of regulatory networks and shape the architecture of
      genomes. Natural selection against their harmful effects has long been considered
      the dominant force limiting their spread. It is now clear that a genome defense
      system of RNA-mediated silencing also plays a crucial role in limiting TE
      proliferation. A full understanding of TE evolutionary dynamics must consider how
      these forces jointly determine their proliferation within genomes. Here I
      consider these forces from two perspectives - dynamics within populations and
      evolutionary games within the germline. The analysis of TE dynamics from these
      two perspectives promises to provide new insight into their role in evolution.

PMID- 21074887
TI  - Motivational interviewing delivered by diabetes educators: does it improve blood
      glucose control among poorly controlled type 2 diabetes patients?
AB  - AIM: To determine whether glycemic control is improved when motivational
      interviewing (MI), a patient-centered behavior change strategy, is used with
      diabetes self management education (DSME) as compared to DSME alone. METHODS:
      poorly controlled type 2 diabetes (T2DM) patients (n=234) were randomized into 4
      groups: MI+DSME or DSME alone, with or without use of a computerized summary of
      patient self management barriers. We compared HbA1c changes between groups at 6
      months and investigated mediators of HbA1c change. RESULTS: study patients
      attended the majority of the four intervention visits (mean 3.4), but drop-out
      rate was high at follow-up research visits (35%). Multiple regression showed that
      groups receiving MI had a mean change in HbA1c that was significantly lower (less
      improved) than those not receiving MI (t=2.10; p=0.037). Mediators of HbA1c
      change for the total group were diabetes self-care behaviors and diabetes
      distress; no between-group differences were found. CONCLUSIONS: DSME improved
      blood glucose control, underlining its benefit for T2DM management. However,
      MI+DSME was less effective than DSME alone. Overall, weak support was found for
      the clinical utility of MI in the management of T2DM delivered by diabetes
      educators.

PMID- 21074889
TI  - The identification of KRAS mutations at codon 12 in plasma DNA is not a
      prognostic factor in advanced non-small cell lung cancer patients.
AB  - BACKGROUND: Qualitative analysis of circulating DNA in the blood is a promising
      non-invasive diagnostic and prognostic tool. Our aim was to study the association
      between the presence of KRAS mutations at codon 12 and several clinical variables
      in advanced non-small cell lung cancer (NSCLC) patients. METHODS: We examined 308
      stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel.
      Blood samples were collected before chemotherapy, and circulating DNA was
      extracted from the plasma using commercial adsorption columns. The KRAS
      mutational status was determined by an RT-PCR method that is based on allelic
      discrimination. RESULTS: The median age of the patients was 60 years [31-80], 84%
      were male, 98% had a performance status of 0-1 and 84% of the patients were in
      stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma
      (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated
      patients, 1% achieved a complete response (CR), 26% achieved a partial response
      (PR), 34% had stable disease (SD) and 39% had progressive disease (PD).
      Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT
      mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found
      in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had
      a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for
      patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p=0.277).
      The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43
      13.70] vs 10.03 months [8.80-11.26] in wt patients (p=0.514). CONCLUSIONS: In
      advanced NSCLC patients, there were no significant differences between patients
      with or without KRAS mutations in plasma-free DNA with respect to the baseline
      characteristics, response rates, PFS or OS.

PMID- 21074890
TI  - Syk mediates BCR- and CD40-signaling integration during B cell activation.
AB  - CD40 is essential for optimal B cell activation. It has been shown that CD40
      stimulation can augment BCR-induced B cell responses, but the molecular
      mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this
      report, we attempted to characterize the signaling synergy between BCR- and CD40
      mediated pathways during B cell activation. We found that spleen tyrosine kinase
      (Syk) is involved in CD40 signaling, and is synergistically activated in B cells
      in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B
      cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk,
      and significantly enhances BCR-induced formation of complex consisting of, Vav-2,
      Btk, BLNK, and phospholipase C-gamma2 (PLC-gamma2) leading to activation of
      extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein
      kinase, Akt, and NF-kappaB required for optimal B cell activation. Therefore, our
      data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively
      modify BCR signaling during B cell activation.

PMID- 21074891
TI  - A functional complement system is required for normal T helper cell
      differentiation.
AB  - Complement is a fundamental part of the innate immune system, and also modulates
      B cell responses. Its effects on T cells, however, are less well studied. Here we
      have studied antigen-specific T cell responses in C3-knockout (C3-KO) C57BL/6
      mice. The animals were immunized with ovalbumin (OVA) in complete Freund's
      adjuvant, which favors T helper 1 (Th1)-type responses. Splenic lymphocytes from
      C3-KO mice proliferated less in response to OVA stimulation than splenocytes from
      control wild type (WT) mice. The response in the C3-KO mice was also
      qualitatively different. The expression of Th1 lineage determining transcription
      factor T-bet was decreased in OVA-stimulated splenocytes, and the induction of
      Th1-associated IgG subclasses impaired. In WT mice T cell proliferation in
      response to OVA was positively correlated with antigen-specific IgG2a and IgG3
      levels. In C3-KO mice the proliferative response correlated with antigen-specific
      IgE levels, consistent with Th2 deviation. The expression of Th1-inducing
      cytokines IL-12 and IFN-gamma was also decreased in the collecting lymph nodes in
      the C3-KO mice after immunization. Our results show that the complement system
      and its component C3 participate in the regulation of T cell responses, and that
      complement function is required for normal T helper cell differentiation.

PMID- 21074892
TI  - Immune modulation of ovalbumin-induced lung injury in mice using beta
      glucosylceramide and a potential role of the liver.
AB  - CD1d-restricted natural killer T (NKT) cells are implicated in the pathogenesis
      of asthma. beta-Glucosylceramide (GC), a naturally occurring lipid, was
      previously shown to alter NKT cell distribution in the liver. We hypothesized
      that GC can affect lung and liver NKT cell distribution and ameliorate asthma.
      Mice were sensitized by intra-peritoneal injection of ovalbumin (OVA) for 2 weeks
      followed by repeated intranasal OVA challenges to induce lung injury mimicking
      asthma. OVA induced asthma groups were either treated by intranasal instillation
      of normal saline, intranasal instillation of GC or inhaled budesonide. To
      investigate the role of the liver, hepatic fibrosis was induced using carbon
      tetrachloride prior to asthma induction. Allergen induced bronchoconstriction was
      measured prior to sacrifice. Isolated lymphocytes from lungs, livers and spleens
      were analyzed for OVA induced proliferation and flow cytometry. Liver and lung
      histology, serum aminotransferase and anti-OVA antibodies level were assessed.
      Treatment with GC significantly reduced OVA induced airway responsiveness
      (p<0.001) similar to inhaled budesonide. GC significantly reduced the peri
      bronchial and peri-vascular inflammatory infiltration mainly through an effect on
      T cells, as suggested by decreased T cell proliferation (p=0.009). Liver CD4 and
      NKT cells significantly increased after GC treatment suggesting liver
      involvement. Inducing hepatic fibrosis blunted the propagation of asthma in spite
      of sufficient increase of serum anti-OVA titers. GC has an immunomodulatory
      effect on a murine model of experimental asthma. We also suggest that the liver
      acts as an immunomodulatory organ and might have a regulatory effect on pulmonary
      diseases.

PMID- 21074893
TI  - Effect of oligogalacturonides on root length, extracellular alkalinization and O2
      -accumulation in alfalfa.
AB  - The effects of an oligogalacturonic acid (OGA) pool on root length of intact
      alfalfa seedlings (Medicago sativa L.), on extracellular pH and on both
      extracellular and intracellular O2- dynamics were examined in this study. Lower
      OGA concentrations (25, 50 and 75 MUg mL-1)promoted root length, but 50 MUg mL-1
      had a stronger effect in promoting growth, while the higher OGA concentration
      (100 MUg mL-1)had no significant effect. Extracellular alkalinization was tested
      only at concentrations higher than 50 MUg mL-1 OGA, showing that the response is
      determined not only by the specific size of OGA, but also by the concentration of
      OGA. The promoting effect of OGA on root growth at 25, 50 and 75 MUg mL-1 OGA
      concentrations in alfalfa root appeared to be unrelated to extracellular
      alkalinization. A possible explanation could be the induction of an O2- burst at
      non-toxic levels, which could drive directly or indirectly several processes
      associated with root elongation in 25, 50 and 75 MUg mL-1 OGA-treated seedlings.
      Analyses using confocal microscopy showed that the increase in the O2-
      generation, mainly in the epidermal cells, induced by 50 MUg mL-1 OGA could be
      related to the promoting effect on root growth. The combination of OGA with DPI
      allowed us to demonstrate that there are different O2--generating sources in the
      epidermal cells of the meristematic zone, likely NADPH oxidase and oxidases or
      oxido-reductase enzymes, insensitive to DPI, that maintain detectable O2-
      accumulation at 60 and 120 min of treatment. These results suggest that OGA
      induce an oxidative burst by several O2--generating sources in the active growth
      zones.

PMID- 21074894
TI  - Longitudinal trends in the performance of scientific peer reviewers.
AB  - STUDY OBJECTIVE: We characterize changes in review quality by individual peer
      reviewers over time. METHODS: Editors at a specialty journal in the top 11% of
      Institute of Scientific Information journals rated the quality of every review,
      using a validated 5-point quality score. Linear mixed-effect models were used to
      analyze rating changes over time, calculating within-reviewer trends plus
      predicted slope of change in score for each reviewer. Reviewers at this journal
      have been shown comparable to those at other journals. RESULTS: Reviews (14,808)
      were performed by 1,499 reviewers and rated by 84 editors during the 14-year
      study. Ninety-two percent of reviewers demonstrated very slow but steady
      deterioration in their scores (mean -0.04 points [-0.8%] per year). Rate of
      deterioration was unrelated to duration of reviewing but moderately correlated
      with mean reviewer quality score (R=0.52). The mean score of each reviewer's
      first 4 reviews predicted subsequent performance with a sensitivity of 75% and
      specificity of 47%. Scores of the group stayed constant over time despite
      deterioration because newly recruited reviewers initially had higher mean quality
      scores than their predecessors. CONCLUSION: This study, one of few tracking
      expert performance longitudinally, demonstrates that most journal peer reviewers
      received lower quality scores for article assessment over the years. This could
      be due to deteriorating performance (caused by either cognitive changes or
      competing priorities) or, to a partial degree, escalating expectations; other
      explanations were ruled out. This makes monitoring reviewer quality even more
      crucial to maintain the mission of scientific journals.

PMID- 21074895
TI  - The relationship between hand area and hand contamination.
AB  - Although the number of colony-forming units (CFUs) on the hands of health care
      workers (HCWs) is a critical measurement in research studies of hand
      contamination, few studies have investigated the correlation between hand area
      and CFU count. In the present study, we calculated the area and measured the
      numbers of CFU on the right hand of 197 HCWs. Our data indicate that close
      relationship between hand area and CFU count.

PMID- 21074896
TI  - Validity and reliability of the proposed core competency for infection control
      nurses of hospitals in Hong Kong.
AB  - Literature review and the Delphi approach were used to draft the core competency
      items of hospital infection control nurses in Hong Kong. Content validity,
      internal consistency, and test-retest reliability of the proposed core competency
      were ensured. The result serves as the foundation of developing training and
      assessment tools for infection control nurses in Hong Kong.

PMID- 21074897
TI  - SIRT1, a histone deacetylase, regulates prion protein-induced neuronal cell
      death.
AB  - Prion diseases associated with the conversion of the cellular prion protein
      (PrP(C)) to the misfolded isoform (PrP(Sc)), affect the central nervous system
      (CNS) of humans and animals. Resveratrol, an activator of class III histone
      deacetylase SIRT1, is important in attenuating cellular injury and oxidative
      stress. The present study investigated the effects of SIRT1 activation on prion
      protein-mediated neuronal cell death and examined its possible signals in
      intracellular apoptotic pathways. Resveratrol treatment significantly increased
      both SIRT1 protein expression and SIRT1 activity and protected neuronal cells
      against PrP (106-126)-induced cell death. Resveratrol-mediated SIRT1 activation
      decreased the acetylation of p53 and p65 induced by prion protein and SIRT1
      inhibitor. SIRT1 activation also inhibited PrP (106-126)-mediated p38 mitogen
      activating protein kinase (MAPK) activation and caspase-3 cleavage, and increased
      the expression of anti-apoptotic Bcl-xL protein. Furthermore, SIRT1
      overexpression by using adenoviral vector protected neuronal cells against PrP
      (106-126). These results indicate that resveratrol inhibits PrP (106-126)-induced
      neuronal cell death by regulating SIRT1 activity and SIRT-related signaling, and
      suggest that prion-related disease may be attenuated by SIRT1 activation or by
      intake of SIRT1-activating molecules.

PMID- 21074899
TI  - Early and late onset Alzheimer's disease patients have distinct patterns of white
      matter damage.
AB  - We investigated patterns of white matter (WM) loss in 18 early onset (EO) and 24
      late onset (LO) Alzheimer's disease (AD) patients compared with 42 healthy
      controls (HC), and explored relationships of WM atrophy and apolipoprotein E
      (ApoE) genotype. Subjects underwent magnetic resonance imaging (MRI). Patterns of
      WM were assessed using voxel-based morphometry. Compared with healthy controls,
      LOAD patients had a selective parahippocampal WM loss, while EOAD patients
      experienced a more widespread pattern of posterior WM atrophy. The distinct
      regional distribution of WM atrophy reflected the topography of gray matter (GM)
      loss. ApoE epsilon4 status was associated with a greater parahippocampal WM loss
      in both AD groups. The greater WM atrophy in EOAD than LOAD fits with the
      evidence that EOAD is a more aggressive form of the disease. The ApoE epsilon4
      effect on WM damage in AD is restricted to specific WM regions and does not seem
      to be related to age of onset.

PMID- 21074898
TI  - Midlife memory improvement predicts preservation of hippocampal volume in old
      age.
AB  - This study examines whether midlife change in episodic memory predicts
      hippocampal volume in old age. From the Seattle Longitudinal Study we
      retrospectively identified 84 healthy, cognitively normal individuals, age 52 to
      87, whose episodic memory had reliably declined (n = 33), improved (n = 28) or
      remained stable (n = 23) over a 14-year period in midlife (age 43-63). Midlife
      memory improvement was associated with 13% larger hippocampal volume (p < 0.01)
      in old age (age 66-87), compared with old age individuals whose midlife episodic
      memory had either declined or remained stable during midlife. Midlife memory
      change did not predict total hippocampal volume for those currently in late
      middle age (age 52-65). The pattern of findings was not modified by gender,
      apolipoprotein epsilon4 status, education or current memory performance. Change
      in midlife memory scores over 14 years, but not any single assessment, predicted
      hippocampal volumes in old age, emphasizing the importance of longitudinal data
      in examining brain-cognition relationships. These findings suggest that
      improvement in memory in midlife is associated with sparing of hippocampal volume
      in later life.

PMID- 21074901
TI  - Education, occupation, leisure activities, and brain reserve: a population-based
      study.
AB  - The influence of education, occupation, and leisure activities on the passive and
      active components of reserve capacity remains unclear. We used the voxel-based
      morphometry (VBM) technique in a population-based sample of 331 nondemented
      people in order to investigate the relationship between these factors and the
      cerebral volume (a marker of brain reserve). The results showed a positive and
      significant association between education, occupation, and leisure activities and
      the cognitive performances on Isaac's set test. Among these factors, only
      education was significantly associated with a cerebral volume including gray and
      white matter (p = 0.01). In voxel-based morphometry analyses, the difference in
      gray matter volume was located in the temporoparietal lobes and in the
      orbitofrontal lobes bilaterally (a p-value corrected <0.05 by false discovery
      rate [FDR]). Although smaller, the education-related difference in white matter
      volume appeared in areas connected to the education-related difference in gray
      matter volume. Education, occupation attainment, and leisure activities were
      found to contribute differently to reserve capacity. Education could play a role
      in the constitution of cerebral reserve capacity.

PMID- 21074900
TI  - Pathogenicity of exonic indels in fused in sarcoma in amyotrophic lateral
      sclerosis.
AB  - Insertion and deletion variants (indels) within poly glycine tracts of fused in
      sarcoma (FUS) were initially reported as causative of disease in amyotrophic
      lateral sclerosis (ALS). Subsequent studies identified similar indels in controls
      and suggested that these indels may confer susceptibility to ALS. We aimed to
      elucidate the role of previously published and novel exonic indels in FUS in an
      extensive cohort of 630 ALS patients and 1063 controls. We detected indels in FUS
      exons 5, 6, 12, and 14 with similar frequencies in patients (0.95%) and controls
      (0.75%). Exonic indels in poly glycine tracts were also observed with similar
      frequencies. The largest indel (p.Gly138_Tyr143del) was observed in 1 control. In
      1 patient, a 3 base pair deletion in exon 14 (p.Gly475del) was identified,
      however in vitro studies did not reveal abnormal localization of p.Gly475del
      mutant FUS. These findings suggest that not all exonic indels in FUS cause
      disease.

PMID- 21074902
TI  - Analysis of optineurin in frontotemporal lobar degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) can occur jointly with amyotrophic
      lateral sclerosis (ALS), and these 2 conditions share a genetic risk factor on
      chromosome 9. It has been reported that mutations in optineurin (OPTN) can cause
      ALS. Therefore, we sequenced OPTN in 371 FTLD cases but no mutations were
      detected, suggesting changes in OPTN do not cause FTLD.

PMID- 21074903
TI  - [Legionellosis in a site with low risk of proliferation].
AB  - After three cases of legionellosis associated with a spa were identified, an
      investigation was conducted to confirm the source of infection, determine the
      risk factors, and establish control measures. Between November 26, 2008 and
      September 16, 2009, six inspections were carried out, samples were collected for
      Legionella pneumophila isolation, and water temperature was determined at all the
      sampling points of the hot water system and at the spa pools. The presence of L.
      pneumophila serogroup 1 with the same molecular pattern as that found in the
      clinical isolate was confirmed in the hot water system (with a low proliferation
      risk according to legislation). The crude attack rate was 0.34% (95% CI: 0.09
      0.94). Samples without L. pneumophila were obtained only after structural changes
      were carried out. Possible factors participating in the cluster were water
      temperatures between 25  degrees C and 30  degrees C, stagnant water and early
      morning exposure.

PMID- 21074905
TI  - [A decade of reflection on health plans in Spain. SESPAS report 2010].
AB  - This article reports the experience of the Working Group of the SESPAS-SCSP
      (Spanish Society of Public Health and Healthcare Administration-Canary Islands
      Society of Public Health) in health policy and planning during the first decade
      of the 21st century and its possible impact on the design of health planning. We
      review the conclusions reached from 2000 to 2008 in the first five Biannual
      Planning and Health Policy meetings that took place during that period. The
      workshops were designed with two speakers who presented different views of the
      subject under discussion, a moderator, who led the debate on the findings, and a
      narrator who served as a notary and also took responsibility for the text summary
      of each table. Two general narrators were responsible for the final wording of
      the conclusions of each workshop or biannual meeting. From 2000 to 2008, there
      were 25 round tables with 121 conclusions and 160 participants. We believe that
      the SESPAS working groups provide multidisciplinary professional values within a
      context of debate in a professional environment, and create spaces for
      reflection, thus helping to improve the health planning system in Spain.

PMID- 21074904
TI  - [Seroepidemiologic study of rubella in childbearing women in Aragon, Spain (2003
      2007)].
AB  - OBJECTIVES: To quantify and identify the rubella-susceptible population in Aragon
      according to sociodemographic variables, with the aim of assessing compliance
      with the 5% limit set by the World Health Organization (WHO). METHODS: Rubella
      serology tests performed in women of childbearing age in the Miguel Servet
      Hospital from 2003 to 2007 were studied. A descriptive analysis of seronegativity
      was performed by age, years of study, and WHO region (for 2007). A logistic
      regression was performed with the independent variables of age and geographical
      origin. RESULTS: We studied 13,136 women. The mean age was 31.2 years. During the
      study period, 5% were susceptible to rubella (95%CI: 4.63-5.37). In 2003, 8.8%
      were seronegative and the highest percentage (12.3%) was found in women aged 15
      to 19 years. The percentage of seronegativity was higher in foreign-born women
      (7.7%), especially those from Asia, than in Spanish women (3.3%; p<0.05).
      CONCLUSIONS: Postpartum preventive strategies should be established to prevent
      possible rubella outbreaks and cases of congenital rubella syndrome.

PMID- 21074906
TI  - Prevention of childhood obesity in Spain: a focus on policies outside the health
      sector. SESPAS report 2010.
AB  - Obesity is currently a global public health problem. Obesity in early life
      increases the risk of long-term energy imbalance and adult obesity and its
      comorbidities, type 2 diabetes, and cardiovascular disease. Since infancy and
      childhood are critical periods for the adoption of food preferences and physical
      activity, prevention strategies must intervene in these early periods to promote
      healthy habits and reduce risk behaviors. Trends in the prevalence of childhood
      obesity and overweight in Spain have continuously increased in the last three
      decades. Obesity and overweight currently affect 15 and 20% of Spanish children,
      respectively, and these percentages are among the highest in Europe. Childhood
      obesity is determined by social and economic factors pertaining to sectors other
      than the health system, such as advertising, the built environment, education and
      the school environment, transportation and the food environment. Following the
      Health in All Policies (HiAP) approach, the authors identified a series of
      multisector policy changes that may help to prevent and control the current
      rising trend of childhood obesity in Spain. The HiAP approach acknowledges that
      social factors including socioeconomic status, gender differences and the work
      life balance are important to develop effective policy changes in the prevention
      of childhood obesity. A key to success in the prevention of childhood obesity in
      Spain through policy changes will depend on the ability to establish a policy
      with the explicit and primary goal of improving health outcomes, despite the
      anticipated resistance from various sectors and stakeholders.

PMID- 21074907
TI  - [Public health in the design of population-based prevention programs in the
      health system. SESPAS report 2010].
AB  - Health systems have been redirected toward effective and equitable health
      policies. Community health and population-based prevention programs with adequate
      quality assurance systems play a key role in this process. In the Spanish
      national health system, these programs involve both public health services and
      clinical care and contribute to their coordination. Population-based prevention
      consists of collective action to protect health, such as public health measures,
      on the government's initiative, and is aimed at the population regardless of the
      insurance system. These preventive interventions should only be implemented when
      measurable criteria of efficiency and equity can be met, with an appropriate
      balance between benefits and harms to avoid iatrogenic effects in the healthy
      population. In population-based programs, public health services can promote
      policies involving intersectoral collaboration on health services, with specific
      interventions on groups through community participation. Population-based
      preventive actions always require coordination and consequently mobilization of
      all the mechanisms between public health and health care is required to provide
      all the entities involved with the information needed to perform their tasks:
      overseeing interventions by both hierarchical structures, feedback,
      standardization of work processes and skills through programs, and mutual
      adjustment through integrated information systems and liaison tools. Population
      based prevention helps to integrate the health system, acts as a cohesive factor
      among regional health services, and demonstrates that a community perspective is
      feasible in Spain.

PMID- 21074908
TI  - Mentoring in nursing education: perceived characteristics of mentors and the
      consequences of mentorship.
AB  - This paper presents the initial research results of mentorship in Flanders,
      Belgium. A validated questionnaire has been used as well as a semi-structured
      interview, to investigate perceived characteristics, advantages and drawbacks of
      mentorship, as well as practical aspects in mentoring education. The
      questionnaire has been validated for the Dutch language. The response rate of 62%
      has been rather high. The ability to give feedback, experience, availability of
      time and a positive attitude were the elements considered important for mentors.
      In spite of workload, lack of time and drawbacks such as adverse effects on the
      team work on the ward, transferring of enthusiasm onto students was still
      possible. Benefits for mentors were immaterial and included closer follow-up of
      new developments, teaching and sharing of experiences. The benefits outweighed
      the drawbacks. Support by mentoring courses, additional study and especially of
      link lecturers proved to be beneficial. Especially the help of link lecturers
      proved to be necessary in problems and in evaluation of "unsafe" students. In the
      latter case, the link lecturer helps to solve the inherent conflict of interest
      by being mentor and assessor at the same time.

PMID- 21074909
TI  - Storytelling and professional learning: a phenomenographic study of students'
      experience of patient digital stories in nurse education.
AB  - This paper reports the findings of a phenomenographic study which sought to
      identify the different ways in which patient digital stories influence students'
      professional learning. Patient digital stories are short multimedia presentations
      that combine personal narratives, images and music to create a unique and often
      emotional story of a patients' experience of health care. While these are
      increasingly used in professional education little is known about how and what
      students learn through engagement with patient digital stories. Drawing upon
      interviews with 20 students within a pre-registration nursing programme in the
      UK, the study identifies four qualitatively different ways in which students
      approach and make sense of patient digital stories with implications for learning
      and professional identity development. Through an identification of the critical
      aspects of this variation valuable insights are generated into the pedagogic
      principles likely to engender transformational learning and patient centred
      practice.

PMID- 21074910
TI  - The immunomodulating enteral nutrition in malnourished surgical patients - a
      prospective, randomized, double-blind clinical trial.
AB  - BACKGROUND & AIM: The immunomodulating nutrition was supposed to reduce the
      incidence of complications in surgical patients, but many authors have questioned
      its value recently. The aim of the study was to assess the impact of enteral
      immunonutrition in postoperative period. METHODS: Between January 2003 and
      December 2009, 305 malnourished patients (123 F, 182 M, m. age 60.8) undergoing
      resection for pancreatic or gastric cancer, after preoperative 14 days of
      parenteral feeding, were randomized in double-blind manner to receive either
      postoperative immunomodulating enteral diet (IMEN) or standard oligopeptide diet
      (SEN). Outcome measures of the intend-to-treat analysis were: number and type of
      complications, length of hospitalization, mortality, and vital organ function.
      RESULTS: Median postoperative hospital stay was 17.1 days in SEN and 13.1 days in
      IMEN group (p = 0.006). Infectious complications were observed in 60 patients
      (39.2%) in SEN and 43 (28.3%) in IMEN group (p = 0.04). Differences were also
      observed in overall morbidity (47.1 vs 33.5%, p = 0.01) and mortality (5.9 vs
      1.3%, p = 0.03), but the ratio of surgical complications, organ function, and
      treatment tolerance did not differ. CONCLUSIONS: The study proved that
      postoperative immunomodulating enteral nutrition should be the treatment of
      choice in malnourished surgical cancer patients. The Clinical Trials Database
      registry number: NCT00576940.

PMID- 21074911
TI  - 210Po in the marine environment with emphasis on its behaviour within the
      biosphere.
AB  - The distribution and behaviour of the natural-series alpha-emitter polonium-210
      in the marine environment has been under study for many years primarily due to
      its enhanced bioaccumulation, its strong affinity for binding with certain
      internal tissues, and its importance as a contributor to the natural radiation
      dose received by marine biota as well as humans consuming seafoods. Results from
      studies spanning nearly 5 decades show that (210)Po concentrations in organisms
      vary widely among the different phylogenic groups as well as between the
      different tissues of a given species. Such variation results in (210)Po
      concentration factors ranging from approximately 10(3) to over 10(6) depending
      upon the organism or tissue considered. (210)Po/(210)Pb ratios in marine species
      are generally greater than unity and tend to increase up the food chain
      indicating that (210)Po is preferentially taken up by organisms compared to its
      progenitor (210)Pb. The effective transfer of (210)Po up the food chain is
      primarily due to the high degree of assimilation of the radionuclide from
      ingested food and its subsequent strong retention in the organisms. In some cases
      this mechanism may lead to an apparent biomagnification of (210)Po at the higher
      trophic level. Various pelagic species release (210)Po and (210)Pb packaged in
      organic biodetrital particles that sink and remove these radionuclides from the
      upper water column, a biogeochemical process which, coupled with scavenging rates
      of this radionuclide pair, is being examined as a possible proxy for estimating
      downward organic carbon fluxes in the sea. Data related to preferential
      bioaccumulation in various organisms, their tissues, resultant radiation doses to
      these species, and the processes by which (210)Po is transferred and recycled
      through the food web are discussed. In addition, the main gaps in our present
      knowledge and proposed areas for future studies on the biogeochemical behaviour
      of (210)Po and its use as a tracer of oceanographic processes are highlighted in
      this review.

PMID- 21074912
TI  - Lower limb coordination patterns in hemiparetic gait: factors of knee flexion
      impairment.
AB  - BACKGROUND: The mechanisms altering knee flexion in hemiparetic gait may be
      neurological (muscle overactivity) or orthopedic (soft tissue contracture) in
      nature, a distinction which is difficult to ascertain clinically during gait.
      This study aimed to distinguish the 2 mechanisms in evaluating thigh-shank
      coordination, which may show instability across the gait cycle in the case of
      bursting rectus femoris overactivity. METHODS: We measured thigh-shank
      coordination in the sagittal plane using the continuous relative phase during
      gait in 15 healthy subjects without and with an orthotic knee constraint (control
      and constrained) and 14 subjects with hemiparesis and rectus femoris overactivity
      before (pre) and after botulinum toxin injection. FINDINGS: Compared with the
      control group, both orthopedic and neurological knee flexion limitations were
      associated with decreased root-mean square of continuous relative phase over
      swing (control, 72.9; constrained, 26.0, P<0.001; pre, 31.3, P<0.001). However,
      only the neurological limitation was characterized by a higher number of
      continuous relative phase reversals over swing (control, 2.3; pre, 4.0; P=0.001)
      and late stance (control, 0.6; pre, 1.7; P<0.001). Botulinum toxin injection was
      associated with a 40% increase in root-mean square of continuous relative phase
      during swing and a 41% decrease in number of continuous relative phase reversals
      during late stance, while peak knee flexion was increased by 31%. INTERPRETATION:
      In hemiparesis, rectus femoris overactivity at swing phase is associated with
      alternating thigh-shank coordination in swing and late stance, which improves
      after botulinum toxin injection. Coordination analysis may help to distinguish
      neurological from orthopedic factors in knee flexion impairment.

PMID- 21074913
TI  - The effect of arch height on kinematic coupling during walking.
AB  - The purpose of the current study was to assess kinematic coupling within the foot
      in individuals across a range of arch heights. Seventeen subjects participated in
      this study. Weight-bearing lateral radiographs were used to measure the arch
      height, defined as angle between the 1st metatarsal and the calcaneus. A
      kinematic model including the 1st metatarsal, lateral forefoot, calcaneus and
      tibia was used to assess foot kinematics during walking. Four coupling ratios
      were calculated: calcaneus frontal to forefoot transverse plane motion (Calcaneal
      EV/Forefoot AB), calcaneus frontal to transverse plane motion (Calcaneus EV/AB),
      forefoot sagittal to transverse plane motion (Forefoot DF/AB), and 1st metatarsal
      sagittal to transverse plane motion (1st Metatarsal DF/AB). Pearson product
      moment correlations were used to assess the relationship between arch height and
      coupling ratios. Mean (SD) radiographic arch angles of 129.8 (12.1) degrees with
      a range from 114 to 153 were noted, underscoring the range of arch heights in
      this cohort. Arch height explained approximately 3%, 38%, 12% and 1% of the
      variance in Calcaneal EV/Forefoot AB, Calcaneus EV/AB, Forefoot DF/AB and 1st
      Metatarsal DF/AB respectively. Calcaneal EV/Forefoot AB, Calcaneus EV/AB,
      Forefoot DF/AB and 1st Metatarsal DF/AB coupling ratios of 1.84 +/- 0.80, 0.56 +/
      0.35, 0.96 +/- 0.27 and 0.43 +/- 0.21 were noted, consistent with the twisted
      foot plate model, windlass mechanism and midtarsal locking mechanisms. Arch
      height had a small and modest relationship with kinematic coupling ratios during
      walking.

PMID- 21074914
TI  - Green roofs as a means of pollution abatement.
AB  - Green roofs involve growing vegetation on rooftops and are one tool that can help
      mitigate the negative effects of pollution. This review encompasses published
      research to date on how green roofs can help mitigate pollution, how green roof
      materials influence the magnitude of these benefits, and suggests future research
      directions. The discussion concentrates on how green roofs influence air
      pollution, carbon dioxide emissions, carbon sequestration, longevity of roofing
      membranes that result in fewer roofing materials in landfills, water quality of
      stormwater runoff, and noise pollution. Suggestions for future directions for
      research include plant selection, development of improved growing substrates,
      urban rooftop agriculture, water quality of runoff, supplemental irrigation, the
      use of grey water, air pollution, carbon sequestration, effects on human health,
      combining green roofs with complementary related technologies, and economics and
      policy issues.

PMID- 21074915
TI  - Annual and seasonal trends of ambient ozone concentration and its impact on
      forest vegetation in Mercantour National Park (South-eastern France) over the
      2000-2008 period.
AB  - In the South-Eastern French Mediterranean region, high ozone concentrations were
      measured since many years and specific symptoms like chlorotic mottles were
      detected on Arolla pines. We presented results for the 2000-2008 period
      concerning the trend analysis for ambient ozone concentrations and related forest
      damages, with the Mann and seasonal Kendall tests. Ozone precursor's emissions
      from Europe have been reduced over the last 20 years. Decreases in annual
      averages, median, 25th and 98th percentiles and maxima values were found. The
      seasonal trend analysis for the high-lying stations showed a decreasing trend for
      the warm season, when main ozone production is the photochemistry, and an
      increase for the cold period, caused by a reduced ozone titration. Statistics on
      Arolla Pine reveal strong correlations between mottling intensity and the high
      ozone concentrations. Finally, decreases for the ozone concentrations, and
      associated statistics, AOT40 values and for the mottling intensity on conifers
      needles were observed.

PMID- 21074916
TI  - Nitrogen leaching and acidification during 19 years of NH4NO3 additions to a
      coniferous-forested catchment at Gardsjon, Sweden (NITREX).
AB  - The role of nitrogen (N) in acidification of soil and water has become relatively
      more important as the deposition of sulphur has decreased. Starting in 1991, we
      have conducted a whole-catchment experiment with N addition at Gardsjon, Sweden,
      to investigate the risk of N saturation. We have added 41 kg N ha(-1) yr(-1) as
      NH(4)NO(3) to the ambient 9 kg N ha(-1) yr(-1) in fortnightly doses by means of
      sprinkling system. The fraction of input N lost to runoff has increased from 0%
      to 10%. Increased concentrations of NO(3) in runoff partially offset the
      decreasing concentrations of SO(4) and slowed ecosystem recovery from acid
      deposition. From 1990-2002, about 5% of the total N input went to runoff, 44% to
      biomass, and the remaining 51% to soil. The soil N pool increased by 5%. N
      deposition enhanced carbon (C) sequestration at a mean C/N ratio of 42-59 g g(
      1).

PMID- 21074917
TI  - Geographic variation in tissue accumulation of endocrine disrupting compounds
      (EDCs) in grazing sheep.
AB  - Muscle tissue was collected from ewes and lambs derived from farms throughout
      Scotland and sample concentrations of five endocrine disrupting compound groups
      were determined. Farms of origin were categorised according to geographic region.
      There were few statistically-significant differences with region or distance from
      cities. However, the magnitude of the difference between the highest and lowest
      mean values in ewe muscle from different regions exceeded 30% for 13 of the 15
      compounds that were consistently detected in muscle, with animals derived from
      the industrialised region having the highest mean values for 11 of the 13
      compounds. A less marked trend was apparent in the lamb muscle (8 of 13 highest
      were in the industrialised region). The physiological effects of such small
      differences in exposure to mixtures of pollutants remain to be determined.

PMID- 21074918
TI  - Bioanalytical and instrumental analysis of thyroid hormone disrupting compounds
      in water sources along the Yangtze River.
AB  - Thyroid hormone (TH) agonist and antagonist activities of water sources along the
      Yangtze River in China were surveyed by a green monkey kidney fibroblast (CV-1)
      cell-based TH reporter gene assay. Instrumental analysis was conducted to
      identify the responsible thyroid-active compounds. Instrumentally derived l
      3,5,3'-triiodothyronine (T(3)) equivalents (T(3)-EQs) and thyroid receptor (TR)
      antagonist activity equivalents referring to dibutyl phthalate (DBP-EQs) were
      calculated from the concentrations of individual congeners. The reporter gene
      assay demonstrated that three out of eleven water sources contained TR agonist
      activity equivalents (TR-EQs), ranging from 286 to 293 ng T(3)/L. Anti-thyroid
      hormone activities were found in all water sources with the TR antagonist
      activity equivalents referring to DBP (Ant-TR-EQs), ranging from 51.5 to 555.3
      MUg/L. Comparisons of the equivalents from instrumental and biological assays
      suggested that high concentrations of DBP and di-2-ethylhexyl phthalate (DEHP)
      were responsible for the observed TR antagonist activities at some locations
      along the Yangtze River.

PMID- 21074919
TI  - Diversity of shrub tree layer, leaf litter decomposition and N release in a
      Brazilian Cerrado under N, P and N plus P additions.
AB  - This study investigated changes in diversity of shrub-tree layer, leaf
      decomposition rates, nutrient release and soil NO fluxes of a Brazilian savanna
      (cerrado sensu stricto) under N, P and N plus P additions. Simultaneous addition
      of N and P affected density, dominance, richness and diversity patterns more
      significantly than addition of N or P separately. Leaf litter decomposition rates
      increased in P and NP plots but did not differ in N plots in comparison to
      control plots. N addition increased N mass loss, while the combined addition of N
      and P resulted in an immobilization of N in leaf litter. Soil NO emissions were
      also higher when N was applied without P. The results indicate that if the
      availability of P is not increased proportionally to the availability of N, the
      losses of N are intensified.

PMID- 21074920
TI  - A longitudinal analysis of the relationship between changes in socio-economic
      status and changes in health.
AB  - In this paper we contribute to discussion on the relationship between different
      aspects of socio-economic status (SES) and health. Separating different aspects
      of SES facilitates the specification of a structural relationship between SES
      indicators and morbidity. Longitudinal data and the utilization of growth curve
      modelling enable an empirical analysis of the direct relationship between changes
      over time in SES indicators and changes in morbidity. Our empirical analysis is
      based on panel data (N = 2976) derived from the annual Swedish Survey of Living
      Conditions. The panel, which consists of respondents that at the first panel wave
      were between 31 and 47 years old, is followed for 16 years, starting in 1979.
      Data are gathered at three points of time. A growth curve model is set up using
      structural equation modelling. The structural relationship and changes over time
      are simultaneously estimated. It is shown that in relation to health occupational
      position is crucial, canalising the effects of class of origin and education.
      More prestigious jobs are related to initially good health and to a less rapid
      deterioration in health. At the same time initial health affects occupational
      mobility, confirming a health selection into less prestigious jobs. It is also
      shown that change of occupation and income are related to change in health. The
      analysis confirms a strong relationship between SES and morbidity and shows that
      initial SES affects later changes in morbidity, i.e., a causal relationship
      exists between SES and morbidity. But, the analysis also demonstrates the
      existence of selection effects, meaning that initial morbidity causes less
      favourable changes in SES. It is finally revealed that changes in occupational
      prestige and income changes co-vary with changes in morbidity. Hence, the
      analysis provides basic information necessary to make any assumption about
      causality and selection in relation to SES and health.

PMID- 21074921
TI  - Experiences of, and attitudes towards, pregnancy and fatherhood amongst
      incarcerated young male offenders: findings from a qualitative study.
AB  - Teenage parenthood is problematised in the UK. Attention is increasingly falling
      on the potential or actual father yet we still know relatively little about young
      men's experiences and attitudes in this area. This paper focuses on the
      experiences of, and attitudes towards, pregnancy and fatherhood amongst a sample
      of men incarcerated in a Scottish Young Offender Institute. In-depth interviews
      were conducted with 40 inmates, aged 16-20, purposively sampled using answers
      from a questionnaire administered to 67 inmates. Twelve men reported eighteen
      pregnancies for which they were, definitely or possibly, responsible. All but one
      of the pregnancies were unplanned. Five of the men were fathers: two were still
      in a relationship with the mother of their child and were in close contact with
      her and the child while incarcerated, three, all of whom had separated from their
      partner before the birth, had had patchy contact with mother and child before
      and/or during their sentence. All five of the men expressed a strong desire to be
      'a good father'. Amongst the interview sample as a whole, most said they did not
      feel ready to become fathers. The main reason given was being unable to fulfil
      what they regarded as the key role of financial provider. Most of the men had
      given little or no thought to the possibility of a sexual partner becoming
      pregnant. Contraceptive use was high, however, amongst the minority who reported
      thinking about this possibility. The paper concludes by considering the cultural
      context of the men's attitudes and the potential for intervention development for
      incarcerated male young offenders in the areas of Sex and Relationships Education
      and parenting.

PMID- 21074922
TI  - Accessing the field: Disability and the research process.
AB  - Disability is as much a factor in interactional dynamics as ethnicity, age,
      gender or sexuality, and therefore its impact on the processes around qualitative
      research warrants much more systematic attention. Disabled researchers are not
      confined to disability studies research, although most accounts of the impact of
      disability on the research process have, thus far, been undertaken within this
      field. This paper moves beyond this narrow focus to consider the impact of
      disabled identities and the embodied experiences of impairment on studies
      involving, primarily, non-disabled people. By reflecting on our experiences as
      visibly disabled researchers, we highlight some of the practical, ethical and
      conceptual dilemmas we encountered. Impairments may assist rapport building with
      participants, but also introduce complex dilemmas concerning whether, when and
      how to disclose them, and the consequences of doing so. We highlight the
      centrality of the visibility of the disabled body in mediating these dilemmas,
      and its part in constraining our responses to them. While we value our commitment
      to positive readings of disability, we demonstrate that disabled researchers
      nevertheless undertake research in contexts where disability is assigned meanings
      disabled people may not share. We argue that all researchers should attend to
      their own 'body signifiers' (whether in relation to ethnicity, wealth, gender,
      age etc.) and embodied experiences of research processes, as these are integral
      to research outcomes, the ethics of research, and are a means by which to address
      power differentials between researcher and participant. This paper addresses a
      gap in the literature, using our experiences of research to highlight the
      negotiations and dilemmas faced by visibly disabled researchers. Negotiations of
      identity prompted by the disabled body in the research process require
      consideration and should not be ignored.

PMID- 21074923
TI  - Unpacking capacity to utilize research: A tale of the Burkina Faso public health
      association.
AB  - One of the most important challenges in addressing global health is for
      institutions to monitor and use research in policy-making. In low- and middle
      income countries (LMICs), civil society organizations such as health professional
      associations can be key contributors to effective national health systems.
      However, there is little empirical data on their capacity to use research. This
      case study was used to gain insight into the factors that affect the knowledge
      translation performance of health professional associations in LMICs by
      describing the organizational elements and processes constituting capacity to use
      research, and examining the potential determinants of this capacity. Case study
      methodology was chosen for its flexibility to capture the multiple and often
      tacit processes within organizational routines. The Burkina Faso Public Health
      Association (ABSP) was studied, using in-depth, semi-structured interviews and
      key documents review. Five key dimensions that affect the association's capacity
      to use research to influence health policy emerged: organizational motivation;
      catalysts; organizational capacity to acquire and organizational capacity to
      transform research findings; moderating organizational factors. Also examined
      were the dissemination strategies used by ABSP and its abilities to enhance its
      capacity through networking, to advocate for more relevant research and to
      develop its potential role as knowledge broker, as well as limitations due to
      scarce resources. We conclude that a better understanding of the organizational
      capacity to use research of health professional associations in LMICs is needed
      to assess, improve and reinforce such capacity. Increased knowledge translation
      potential may leverage research resources and promote knowledge-sharing.

PMID- 21074925
TI  - Fading-figure tracing in Williams syndrome.
AB  - Williams syndrome (WS) is a neurodevelopmental disorder characterized by severe
      impairment of visuospatial abilities. Figure-drawing abilities, which are thought
      to reflect visuospatial abilities, have yet to be fully investigated in WS. The
      purpose of the present study was to clarify whether drawing abilities differ
      between WS individuals and typically developing children (TD). We compared the
      performance of two groups of subjects (WS, mean age 16 years; TD, 5-6 years of
      age) using a fading-figure tracing task that requires subjects to trace a target
      figure that is gradually disappearing from a PC screen. Although the TD group
      exhibited clearly improved performance with long fading time, the WS group did
      not. Moreover, the TD group exhibited poor performance for figures with more than
      six angles, regardless of the figure type (e.g. closed or open), whereas the WS
      group exhibited generally poor performance for figures with more than five angles
      but relatively preserved performance for open figures. These findings indicate
      that a combination of decreased visuospatial span associated with incomplete
      development of visual scanning and disproportionate development of global
      processing may cause drawing disabilities in WS.

PMID- 21074924
TI  - Do early-life conditions predict functional health status in adulthood? The case
      of Mexico.
AB  - Relatively few researchers have investigated early antecedents of adult
      functional limitations in developing countries. In this study, we assessed
      associations between childhood conditions and adult lower-body functional
      limitations (LBFL) as well as the potential mediating role of adult socioeconomic
      status, smoking, body mass index, and chronic diseases or symptoms. Based on data
      from the Mexican Health and Aging Study (MHAS) of individuals born prior to 1951
      and contacted in 2001 and 2003, we found that childhood nutritional deprivation,
      serious health problems, and family background predict adult LBFL in Mexico.
      Adjustment for the potential mediators in adulthood attenuates these associations
      only to a modest degree.

PMID- 21074926
TI  - Assessment of chest rise during mask ventilation of preterm infants in the
      delivery room.
AB  - BACKGROUND: Current neonatal resuscitation guidelines recommend using visual
      assessment of chest wall movements to guide the choice of inflating pressure
      during positive pressure ventilation (PPV) in the delivery room. The accuracy of
      this assessment has not been tested. We compared the assessment of chest rise
      made by observers standing at the infants' head and at the infants' side with
      measurements of tidal volume. METHODS: Airway pressures and expiratory tidal
      volume (V(Te)) were measured during neonatal resuscitation using a respiratory
      function monitor. After 60s of PPV, resuscitators standing at the infants' head
      (head view) and at the side of the infant (side view) were asked to assess chest
      rise and estimate V(Te). These estimates were compared with V(Te) measurements
      taken during the previous 30s. RESULT: We studied 20 infants who received a mean
      (SD) of 23 (4) inflations during the 30s. Some observer felt unable to assess
      chest rise both from the head view (6/20) and from the side view (3/20).
      Observers from both head and side tended to underestimate tidal volume by 3.5mL
      and 3.3mL respectively. Agreement between clinical assessment and measured V(Te)
      was generally poor. CONCLUSION: During mask ventilation, resuscitators were
      unable to accurately assess chest wall movement visually from either head or side
      view.

PMID- 21074927
TI  - The incidence and significance of accidental hypothermia in major trauma--a
      prospective observational study.
AB  - BACKGROUND: Serious sequelae have been associated with injured patients who are
      hypothermic (<35 degrees C) including coagulopathy, acidosis, decreased
      myocardial contractility and risk of mortality. AIM: Establish the incidence of
      accidental hypothermia in major trauma patients and identify causative factors.
      METHOD: Prospective identification and subsequent review of 732 medical records
      of major trauma patients presenting to an Adult Major Trauma Centre was
      undertaken between January and December 2008. Multivariate analysis was performed
      using logistic regression. Significant and clinically relevant variables from
      univariate analysis were entered into multivariate models to evaluate
      determinants for hypothermia and for death. Goodness of fit was determined with
      the use of the Hosmer-Lemeshow statistic. MAIN RESULTS: Overall mortality was
      9.15%. The incidence of hypothermia was 13.25%. The mortality of patients with
      hypothermia was 29.9% with a threefold independent risk of death: OR (CI 95%)
      3.44 (1.48-7.99), P = 0.04. Independent determinants for hypothermia were pre
      hospital intubation: OR (CI 95%) 5.18 (2.77-9.71), P < 0.001, Injury Severity
      Score (ISS): 1.04 (1.01-1.06), P = 0.01, Arrival Systolic Blood Pressure (ASBP) <
      100 mm Hg: 3.04 (1.24-7.44), P = 0.02, and winter time: 1.84 (1.06-3.21), P =
      0.03. Of the 87 hypothermic patients who had repeat temperatures recorded in the
      Emergency Department, 77 (88.51%) patients had a temperature greater than the
      recorded arrival temperature. There was no change in recorded temperature for
      four (4.60%) patients, whereas six (6.90%) patients were colder at Emergency
      Department discharge. CONCLUSION: Seriously injured patients with accidental
      hypothermia have a higher mortality independent of measured risk factors. For
      patients with multiple injuries a coordinated effort by paramedics, nurses and
      doctors is required to focus efforts toward early resolution of hypothermia
      aiming to achieve a temperature >35  degrees C.

PMID- 21074928
TI  - Trichostatin A inhibits TGF-beta1 induced in vitro chondrogenesis of hMSCs
      through Sp1 suppression.
AB  - Trichostatin A (TSA) is a histone deacetylase inhibitor (HDACi) known to modulate
      differentiation of many cells. However, its effect on chondrogenesis remains
      elusive. This study was aimed to investigate the effects of TSA on in vitro
      transforming growth factor-beta1 (TGF-beta1)-induced chondrogenesis of human
      mesenchymal stem cells (hMSCs). The pellet cultures of hMSCs in a chondrogenic
      medium were exposed to TGF-beta1 and TSA. Quantitative reverse
      transcription/polymerase chain reaction (PCR) analysis, Alcian blue staining, and
      immunohistochemistry staining were used to confirm and compare the differences in
      chondrogenesis by analyzing the mRNA of chondrogenic genes (Sox9, Aggrecan, and
      Col2A1), synthesis of chondrogenic proteins and type II collagen, respectively.
      TGF-beta1 signaling and its downstream targets were determined by western blot
      analysis. TGF-beta1 led to significant increases in chondrogenic gene expression
      and the synthesis of chondrogenic proteins. However, TSA significantly decreased
      chondrogenic gene expression and the synthesis of chondrogenic proteins in a dose
      dependent manner. TGF-beta1 increased phosphorylation of Smad 2/3 and Sp1
      expression around half an hour after induction. The increase of Sp1, but not Smad
      2/3 activation was almost completely blocked by the addition of TSA. The
      chondrogenic effect of TGF-beta1 was also suppressed by the Sp1-binding inhibitor
      mithramycin A. Finally, overexpression of Sp1 abolished TSA-mediated inhibition
      of TGF-beta1-induced chondrogenesis. Our study showed that TSA inhibited
      chondrogenesis through inhibition of TGF-beta1-induced Sp1 expression.
      Furthermore, Sp1 could be a useful tool in future studies looking into biological
      mechanisms by which chondrogenesis of hMSCs can be augmented, especially in the
      area of clinical application.

PMID- 21074929
TI  - Respiration indices and stability measurements of compost through electrolytic
      respirometry.
AB  - An experimental technique for compost stability measurements based on Sapromat
      electrolytic respirometry was optimised and subsequently applied to a sludge
      composting process. Anaerobically digested sewage sludge mixed with reed was
      composted during 90 days in a pilot-scale rotary drum with forced aeration.
      Periodic solid samples were taken, and a previously optimised respirometric
      procedure was applied in order to measure the oxygen consumption. The
      respirometric experiments were made directly with a few grams of solid samples,
      optimum moisture and 37  degrees C over a period of 96 h. The results obtained
      showed how the respiration activity of the sludge decreased during the composting
      experiment under the specific operating conditions. The specific oxygen uptake
      rate (SOUR) instant values from the oxygen consumption curves were obtained, and
      two commonly used respirometric indexes (RI(24) and AT(4)) were calculated for
      all samples. Both RI(24) (a mean of the SOUR values during the 24 h maximum
      activity period) and AT(4) (total oxygen consumption after 4 days) were the
      recommended parameters for the estimation of compost stability by the European
      Union in the second draft of the Working Document on the Biological Treatment of
      Biowaste in 2001. Both indexes exponentially decreased with the composting time,
      and a good linear correlation between them was observed. Final values of RI(24)
      and AT(4) after 90 days were 600 mg O(2) kg VS(-1) h(-1) and 26 mg O(2) gTS(-1),
      respectively. We also considered if this technique could be classified as a
      Dynamic or Static method, the two primary respirometric techniques for measuring
      compost stability. Supposing that the proposed procedure is considered a dynamic
      method (no limitations on the amount of oxygen supply), the final RI(24) obtained
      was compared with the dynamic respiration index (DRI) proposed by the EU (1000 mg
      O(2) kg VS(-1) h(-1)). Our result indicated that stable compost was obtained
      after 90 d. However, if a static limit was considered (AT(4) lower than 10 mg
      O(2) gTS(-1) as proposed by the EU), our result would indicate that more
      residence composting time would be needed. Taking into account these results, the
      advantages and disadvantages and the validity of the proposed method are
      discussed.

PMID- 21074930
TI  - Passive and active adaptive management: approaches and an example.
AB  - Adaptive management is a framework for resource conservation that promotes
      iterative learning-based decision making. Yet there remains considerable
      confusion about what adaptive management entails, and how to actually make
      resource decisions adaptively. A key but somewhat ambiguous distinction in
      adaptive management is between active and passive forms of adaptive decision
      making. The objective of this paper is to illustrate some approaches to active
      and passive adaptive management with a simple example involving the drawdown of
      water impoundments on a wildlife refuge. The approaches are illustrated for the
      drawdown example, and contrasted in terms of objectives, costs, and potential
      learning rates. Some key challenges to the actual practice of AM are discussed,
      and tradeoffs between implementation costs and long-term benefits are
      highlighted.

PMID- 21074931
TI  - Reuse of ornamental rock-cutting waste in aluminous porcelain.
AB  - Large amounts of solid wastes are discarded in the ornamental rocks industry.
      This work investigates the incorporation of ornamental rock-cutting waste as a
      raw material into an aluminous porcelain body, replacing natural feldspar
      material by up to 35 wt.%. Formulations containing rock-cutting waste were
      pressed and sintered at 1350  degrees C. The porcelain pieces were tested to
      determine their properties (linear shrinkage, water absorption, apparent density,
      mechanical strength, and electrical resistivity). Development of the
      microstructure was followed by scanning electron microscopy (SEM) and X-ray
      diffraction (XRD) analyses. The results showed that ornamental rock-cutting waste
      could be used in aluminous porcelains, in the range up to 10 wt.%, as a partial
      replacement for traditional flux material, resulting in a valid route for
      management of this abundant waste.

PMID- 21074932
TI  - Water water everywhere, but not enough for salmon? Organizing integrated water
      and fisheries management in Puget Sound.
AB  - Natural resource management has traditionally been organized within discrete
      land, water, and fishery resource sectors. However, emerging environmental
      problems often cross these boundaries, and managers have struggled to find
      effective planning approaches for multi-resource concerns. No case better
      exemplifies these challenges than efforts to ensure sufficient flows of water for
      salmon in the Pacific Northwest. In this study, we investigate the organizational
      experiences of collaborative water and salmon recovery planning groups in the
      Puget Sound region of Washington. Using conceptual frameworks from organizational
      sociology, we examine how different regulative, normative, and cultural-cognitive
      institutional forces shape the structure and behavior of both water and salmon
      recovery planning groups. Data obtained through content analysis of planning
      documents and interviews with natural resource planners illustrate that legal
      structures, shared intra-group norms, and the distinct organizational cultures of
      water and salmon recovery groups constrain these organizations' ability to
      address linked water-for-salmon concerns. These findings illustrate that
      assessing institutional and organizational arrangements may be equally as
      important as understanding hydrology and biology when attempting to forward an
      integrated approach to water and fisheries management.

PMID- 21074933
TI  - Preventing land loss in coastal Louisiana: estimates of WTP and WTA.
AB  - A dichotomous-choice contingent-valuation survey was conducted in the State of
      Louisiana (USA) to estimate compensating surplus (CS) and equivalent surplus (ES)
      welfare measures for the prevention of future coastal wetland losses in
      Louisiana. Valuations were elicited using both willingness to pay (WTP) and
      willingness to accept compensation (WTA) payment vehicles. Mean CS (WTP)
      estimates based on a probit model using a Box-Cox specification on income was
      $825 per household annually, and mean ES (WTA) was estimated at $4444 per
      household annually. Regression results indicate that the major factors
      influencing support for land-loss prevention were income (positive, WTP model
      only), perceived hurricane protection benefits (positive), environmental and
      recreation protection (positive), distrust of government (negative), age
      (positive, WTA model only), and race (positive for whites).

PMID- 21074934
TI  - Almond tree and organic fertilization for soil quality improvement in southern
      Italy.
AB  - The semi-arid Mediterranean region, characterized by long dry periods followed by
      heavy bursts of rainfall, is particularly prone to soil erosion. The main goal of
      this study is to evaluate the soil quality under different practices of bio
      physical amelioration which involve the soil-plant system (almond trees) and
      microorganism-manure. This study, carried out in the South of Italy (Basilicata
      Region- Pantanello farm), considered two types of fertilization (mineral and
      organic) and three slope gradients (0, 2 and 6%), in order to evaluate the
      effects of management practices in resisting soil erosion. Chemical (organic
      carbon and nitrogen), physical (soil shrinkage and bulk density) and biochemical
      (dehydrogenase activity and hydrolytic enzyme activities) parameters were
      selected as markers to follow agro-ecological changes with time. The organic
      treatment affected soil microbiological and physico-chemical properties by
      increasing soil nutrient availability, microbial activity, and improving soil
      structure. The consistently higher values of the hydrolytic enzyme activities
      (beta-glucosidase, phosphatase, urease and protease) often observed in the
      presence of plants and on the 0 and 2% slopes, suggested the stimulation of
      nutrient cycles by tree roots, which improve the conditions for soil
      microorganisms in carrying out their metabolic activity. In the 6% slope and, in
      particular, in the mineral fertilizer treatment, soil metabolism was lower as
      suggested by the dehydrogenase activity which was 50% lower than that found in
      the 0 and 2% slopes, this seemed to be related to a slowdown in the nutrient
      cycling and organic carbon metabolism. However, on this slope, in both mineral
      and organic treatments, a significant stimulation of hydrolytic enzyme activities
      and an improvement of soil structure (reduction of bulk density of about 10% and
      increase in total shrinkage from 20 to 60%) were observed with plants compared to
      the control soil. The combination of organic fertilization and almond trees
      resulted effective, also in the highest slope, in mitigating the degradation
      processes through the improvement of chemico-nutritional, biochemical and
      physical soil properties.

PMID- 21074935
TI  - Screening for thermotolerant ligninolytic fungi with laccase, lipase, and
      protease activity isolated in Mexico.
AB  - The State of Hidalgo (Mexico) has a large area of forests known as the Huasteca
      Hidalguense, with a large variety of microorganisms inhabiting it. They represent
      an important resource from the ecological and technological point of view because
      they can be used in a broad variety of industrial processes. Due to the climatic
      conditions of this region, fungi inhabiting it must be thermophile or, at least,
      thermotolerant, as temperatures can be higher than 45 degrees C in the summer,
      declining to 20 degrees C in the winter. Use of ligninolytic fungi relies on
      their capacity to produce enzymes of industrial interest, a topic that has been
      under continuous research by academic and industrial investigators. Among the
      most important enzymes are proteases that are widely used due to their
      biotechnological applications with a high economic impact. Other enzymes,
      laccases, peroxidases, and lipases are of interest for the industries of the
      state of Hidalgo, especially in the textile industry, specifically in effluent
      processing. Fungi (n=156) were collected in the Huasteca Hidalguense, of which
      100 were isolated in potato-dextrose-agar covered plates and maintained in tilted
      tubes. Afterwards, enzymatic activity (laccase, protease and lipase) was
      determined in the plates. The purpose was to select those fungi with the highest
      potential for biotechnological applications. Fungi generally grew at either 30
      degrees C or 37 degrees C, and for some isolates enzymatic activities were
      detected at this higher temperature. Results are presented as the relation
      between enzymatic activity and growth rate: 60 fungi presented laccase activity,
      49 had lipase activity, and none had protease activity. In most cases, enzymatic
      activity was higher than the growth rate, indicating that the isolated fungi have
      a great biotechnological potential. Statistical analysis revealed that isolates
      31 (Trametes) and 8.1 (unidentified) have a larger potential to be studied as
      laccase-producing fungi. On the other hand, isolates 144.2 (Fomes), 154
      (Trametes), and 147.2 (Pycnoporus) are of interest as lipase activity producers,
      an activity scarcely studied in this type of microorganisms.

PMID- 21074936
TI  - Imatinib treatment in chronic myelogenous leukemia: What have we learned so far?
AB  - Imatinib mesylate is currently the standard therapy for chronic myelogenous
      leukemia patients. Despite the remarkable results achieved with imatinib, the
      emergence of resistance to this drug has become a significant problem. Actually,
      two other second-generation tyrosine kinase inhibitors have been used for
      resistant/intolerant patients to imatinib. With the availability of oral tyrosine
      kinase inhibitors for the treatment of chronic myelogenous leukemia, questions
      relating to adherence to prescribed therapy have become an important issue. It
      has been demonstrated that the effectiveness of the treatment with imatinib
      requires high compliance to the prescribed dose of the drug for an indefinite
      period of time, whereas reduced adherence to therapy has been associated with
      delay in achieving cytogenetic or molecular response and/or possible development
      of resistance. The aim of this review is to discuss the importance of adherence,
      and the possible tools that we have to measure it, to improve our knowledge on
      possible underlying causes of non-adherence and the impact of non-adherence on
      hospitalization risk and healthcare cost through a systematic review of the data
      published to date.

PMID- 21074937
TI  - Synthesis of a novel layered double hydroxides [MgAl(4)(OH)(12)](Cl)(2).2.4H(2)O
      and its anion-exchange properties.
AB  - A novel layered double hydroxide of Mg and Al with composition
      [Mg(0.96)Al(4.00)(OH)(12)]Cl(1.86)(CO(3))(0.03).2.4H(2)O, designated as MgAl(4)
      Cl, was synthesized by mixing crystalline gibbsite (gamma-Al(OH)(3)) and solid
      MgCl(2).6H(2)O with subsequent hydrothermal treatment at 160  degrees C for 72h.
      The MgAl(4)-Cl exhibited a crystalline material of a layered structure, as
      evidenced from X-ray diffraction. Anion uptake experiments with the MgAl(4)-Cl
      showed that Cl(-) in the interlayer space can be exchanged with anions such as
      Br(-), H(2)PO(4)(-), CO(3)(2-) or dodecyl sulfate (DS(-)) from aqueous solutions
      with preservation of the layered structure. Uptake of NO(3)(-), BrO(3)(-) or
      SO(4)(2-) on the MgAl(4)-Cl showed different behavior; these anions can be
      exchanged within 1h maintaining the layered structure, but a release of Mg(2+)
      cations from the sample was observed with increased reaction time, resulting in
      collapse of the layered structure and formation of the gibbsite phase, as
      determined from chemical analyses and X-ray diffraction.

PMID- 21074938
TI  - Novel Bi(2)WO(6)-TiO(2) heterostructures for Rhodamine B degradation under
      sunlike irradiation.
AB  - Highly efficient Bi(2)WO(6)-TiO(2) heterostructure is synthesized by means of a
      hydrothermal method having highly photoactivity for the degradation of Rhodamine
      B under sunlike irradiation. From the structural characterization it has been
      demonstrated that TiO(2) is incorporated on the Aurivillius structure.
      Interesting synergetic effect between TiO(2) and Bi(2)WO(6) leads to an improved
      charge carrier separation mechanism, causing the excellent photocatalytic
      performance under sunlike irradiation. The photocatalytic performance of
      Bi(2)WO(6) and Bi(2)WO(6)-TiO(2) was compared under different irradiation
      conditions and using increasing Rhodamine B concentration up to 25 ppm. After the
      photocatalytic analysis of both systems, the mineralization efficiency of the
      heterostructure appears significantly higher with respect to Bi(2)WO(6).

PMID- 21074939
TI  - Pyridine appended L-methionine: a novel chelating resin for pH dependent Cr
      speciation with scanning electron microscopic evidence and monitoring of yeast
      mediated green bio-reduction of Cr(VI) to Cr(III) in environmental samples.
AB  - Chemical speciation and pH dependent separation of Cr(III) and Cr(VI) species in
      environmental samples have been achieved by solid phase extraction using a new
      chelating resin containing pyridine appended L-methionine. Cr(III) is completely
      sorbed on the resin at pH 8.0 and Cr(VI) at pH 2.0. Hence a pH dependent
      separation of Cr(III) and Cr(VI) is possible with a limit of detection of 1.6 MUg
      mL(-1) and 0.6 MUg mL(-1) respectively. The sorption capacity of the resin for
      Cr(III) and Cr(VI) is 2.8 mmol g(-1) and 1.3 mmol g(-1) respectively. The
      sorption of chromium on the resin is supported by scanning electron microscopy
      (SEM). Complete desorption of Cr(III) and Cr(VI) from 1g of Cr loaded resin was
      achieved using 10 mL of 2 mol L(-1) HNO(3) and 6 mL of 3 mol L(-1) HNO(3)
      respectively. Quantitative recoveries of Cr(III) (pH 8.0) and Cr(VI) (pH 2.0)
      were found to be 96.0% and 98.0% respectively. Reduction efficiency of
      Rhodotornula mucilaginosa yeast from Cr(VI) to Cr(III) was monitored with this
      new resin. Concentrations of metal ions were measured by flame atomic absorption
      spectroscopy (FAAS).

PMID- 21074940
TI  - Removal of phenols in water using chitosan-conjugated thermo-responsive polymers.
AB  - A chitosan-conjugated thermo-responsive polymer containing 15% chitosan, PNIPAAm
      15CS, was used for the removal of different phenols in water. The polymer was
      synthesized by a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-mediated
      condensation of poly(N-isopropylacrylamide-co-acrylic acid) and chitosan in the
      aqueous solution (pH 6). At 30  degrees C, phenol, 4-methylphenol, 4
      methoxyphenol, and 4-chlorophenol were converted to dark brown oxidized compounds
      by the tyrosinase-induced enzymatic reaction and subsequently bound to the amino
      moiety of PNIPAAm-15CS. In the presence of 1.0 g L(-1) PNIPAAm-15 CS and 50 k UL(
      1) tyrosinase, phenols (20 mg L(-1)) decreased to undetectable levels (<0.01 mg
      L(-1)) within 2h. By the vigorous mixing of the solution at 40  degrees C, the
      polymer deposited and became a small coagulate that can be easily taken up from
      water. Accompanying the polymer deposition, the oxidized compounds were
      completely (>98%) removed. The proposed method was successfully applied to the
      removal of phenols from wastewaters.

PMID- 21074941
TI  - Assessing the characteristics of groundwater quality of arsenic contaminated
      aquifers in the blackfoot disease endemic area.
AB  - Redox couples approach and multivariate statistical techniques, including factor
      analysis, cluster analysis and discriminant analysis, were applied to evaluate
      and to interpret the complex groundwater quality in the blackfoot disease endemic
      area, Taiwan. Most groundwater samples were characterized as Na-Ca-HCO(3) with
      HCO(3)(-) as the dominant anion. Total arsenic (As) concentration, predominantly
      as As(3+), ranged from <1.0 to 562.7 MUg/L. The patterns of measured reducing
      potential were consistent with those values calculated from As couple, revealing
      the in situ environment enhanced the accumulation of As concentration in the
      groundwater. Factor analysis proposed a four-factor model, comprising salination,
      reductive dissolution of Fe/Mn oxyhydroxides, As reduction and chemical potential
      factor, and explained 89.94% of total variance in groundwater. Furthermore, two
      factors, reductive dissolution of Fe/Mn oxyhydroxides and As reduction, suggested
      that the decoupled reductive processes accounted for high As concentration in
      this area. Cluster analysis was adopted to spatially categorize the sampled wells
      into three main clusters and characterized by the factor scores of the four
      factor model. Two-parameter (pH and Eh) model derived from discriminant analysis
      can be used for preliminary assessment to determine whether the As concentration
      exceeds 10 MUg/L with simple field measurements in this area.

PMID- 21074942
TI  - Metal leaching from monolithic stabilised/solidified air pollution control
      residues.
AB  - Portland cement (CEM I) and ground granulated blast furnace slag (ggbs) have been
      used to treat air pollution control (APC) residues from an energy-from-waste
      plant burning municipal solid waste. Stabilised/solidified (s/s) products were
      prepared with binder additions ranging from 10 to 50 wt.% of total dry mass and
      water/solids ratios between 0.40 and 0.80. Monolithic leach tests (EA NEN
      7375:2004) indicated that 50% binder additions were necessary to meet the UK
      monolithic Waste Acceptance Criteria (monWAC) for Pb and Zn, and previous work
      indicated that chloride leaching exceeded WAC even at this binder addition. Lower
      binder additions (20 and 10%) did not sufficiently reduce leaching of Pb.
      Although the monWAC are based on an assumption that leaching is diffusion
      controlled, evaluation of leaching mechanisms indicates that more complex
      processes than diffusion occur for s/s APC residues.

PMID- 21074943
TI  - Photodegradation and toxicity changes of antibiotics in UV and UV/H(2)O(2)
      process.
AB  - The photodegradation of three antibiotics, oxytetracycline (OTC), doxycycline
      (DTC), and ciprofloxacin (CIP) in UV and UV/H(2)O(2) process was investigated
      with a low-pressure UV lamp system. Experiments were performed in buffered
      ultrapure water (UW), local surface water (SW), and treated water from local
      municipal drinking water treatment plant (DW) and wastewater treatment plant
      (WW). The efficiency of UV/H(2)O(2) process was affected by water quality. For
      all of the three selected antibiotics, the fastest degradation was observed in
      DW, and the slowest degradation occurred in WW. This phenomenon can be explained
      by R(OH,UV), defined as the experimentally determined OH radical exposure per UV
      fluence. The R(OH,UV) values represent the background OH radical scavenging in
      water matrix, obtained by the degradation of para-chlorobenzoic acid (pCBA), a
      probe compound. In natural water, the indirect degradation of CIP did not
      significantly increase with the addition of H(2)O(2) due to its effective
      degradation by UV direct photolysis. Moreover, the formation of several
      photoproducts and oxidation products of antibiotics in UV/H(2)O(2) process was
      identified using GC-MS. Toxicity assessed by Vibrio fischer (V. fischer), was
      increased in UV photolysis, for the photoproducts still preserving the
      characteristic structure of the parent compounds. While in UV/H(2)O(2) process,
      toxicity increased first, and then decreased; nontoxic products were formed by
      the oxidation of OH radical. In this process, detoxification was much easier than
      mineralization for the tested antibiotics, and the optimal time for the
      degradation of pollutants in UV/H(2)O(2) process would be determined by parent
      compound degradation and toxicity changes.

PMID- 21074944
TI  - Arsenic stability in arsenopyrite-rich cemented paste backfills: a leaching test
      based assessment.
AB  - Arsenic (As) is a toxicant in tailings from sulphur deposits. It represents an
      environmental risk because of its high solubility. Tailings can be mixed with
      water (typically 25%) and a low proportion of hydraulic binder (3-7%) to produce
      a cemented paste backfill (CPB), stored in underground mine openings. CPB is a
      tailings storage technique, but it could also provide environmental advantages by
      stabilization of polluting elements such as As. Tailings from Casa Berardi mine
      (QC, Canada) contain As (3800 ppm), mainly in arsenopyrite form. For this study,
      three different CPBs were synthesized in laboratory using Casa Berardi tailings
      and three different binders. These pastes were submitted to various leaching
      tests after 28 days of curing. The results indicate that As is released at higher
      concentration for a fly ash-based CPB than for slag- and Portland cement-based
      CPB. However, at lower pH, As is better stabilized in fly ash-based samples.
      These differences can be explained by a variation of solubility of As-compounds
      in each CPB. Several mechanisms of As release occur, as diffusion and/or
      dissolution/precipitation. The accelerated weathering test results show that
      sulphide reactivity is buffered by the neutralizing minerals contained in CPB,
      and influence the As release behaviour by decreasing the oxidation of As-bearing
      sulphides.

PMID- 21074945
TI  - Haemoparasite prevalence and Theileria parva strain diversity in Cape buffalo
      (Syncerus caffer) in Uganda.
AB  - Cape buffalo (Syncerus caffer) are considered to be an important reservoir for
      various tick-borne haemoparasites of veterinary importance. In this study we have
      compared the haemoparasite carrier prevalence in buffalo from four geographically
      isolated national parks in Uganda [Lake Mburo National Park (LMNP), Queen
      Elizabeth National Park (QENP), Murchison Falls National Park (MFNP) and Kidepo
      Valley National Park (KVNP)]. Differences were seen in haemoparasite prevalence
      in buffalo from the four national parks. All the buffalo sampled in LMNP were
      carriers of Theileria parva however, buffalo from MFNP and KVNP, which are both
      located in the north of Uganda, were negative for T. parva. Interestingly, 95% of
      buffalo in the northern part of QENP were T. parva positive, however all buffalo
      sampled in the south of the park were negative. A high multiplicity of infection
      was recorded in all the buffalo found to be carrying T. parva, with evidence of
      at least nine parasite genotypes in some animals. Most of the buffalo sampled in
      all four national parks were carriers of T. mutans and T. velifera, however none
      were carriers of T. taurotragi, Babesia bovis, Babesia bigemina, Ehrlichia bovis
      or Ehrlichia ruminantium. All the buffalo sampled from LMNP were positive for T.
      buffeli and T. sp. (buffalo) however, buffalo from the parks in the north of the
      country (KVNP and MFNP) were negative for these haemoparasites. Anaplasma
      centrale and Anaplasma marginale were circulating in buffalo from all four
      national parks. T. parva gene pools from two geographically separated populations
      of buffalo in two of the national parks in Uganda (LMNP and QENP) were compared.
      The T. parva populations in the two national parks were distinct, indicating that
      there was limited gene flow between the populations. The results presented
      highlight the complexity of tick-borne pathogen infections in buffalo and the
      significant role that buffalo may play as reservoir hosts for veterinary
      haemoparasites that have the potential to cause severe disease in domestic
      cattle.

PMID- 21074946
TI  - Angiogenic suppression of osteoclasts may play a role in developing
      bisphosphonate-related osteonecrosis of the jaw.
AB  - Since it was firstly reported in 2003, a large number of cases have been
      published concerning bisphosphonate-related osteonecrosis of the jaw (BRONJ). It
      has generated great interest in the medical and research communities yet remains
      an enigma, given its unknown pathogenesis. Many hypotheses concerning the
      underlying pathophysiology are discussed, including two most popular hypotheses:
      bone remodeling suppression and angiogenesis suppression, but none of them could
      explain all the unique characters of BRONJ. Bisphosphonates are potent osteoclast
      inhibitors, and recent studies revealed that osteoclasts were important for bone
      angiogenesis. Therefore, we hypothesize that bisphosphonates could inhibit
      osteoclast stimulation of angiogenesis, which plays an important role in
      developing BRONJ. Our hypothesis could help to explain some unintelligible
      characters of BRONJ, and deserves further studies.

PMID- 21074947
TI  - The role of sarcoplasmic protein in hydrostatic pressure-induced myofibrillar
      protein denaturation.
AB  - To observe the role of sarcoplasmic protein (SP) on myofibrillar protein (MP)
      denaturation under a hydrostatic pressure (HP), MP isolated from bovine muscle
      was treated with 300 MPa by increasing concentrations of SP (0, 0.8, 1.6, and 3.2
      mg/ml) from bovine. SDS-PAGE patterns of soluble proteins in 0.1M NaCl (pH 7.4)
      indicated that a protein (about 100 kDa) from MP decreased with increasing
      concentrations of SP and that a 97 kDa protein from SP observed with 0.1 MPa was
      not observed with 300 MPa. SDS-PAGE patterns of soluble proteins in 0.6 M NaCl
      (pH 7.4) and Ca-ATPase activity showed that the denaturation of myosin heavy
      chain (MHC) was accelerated with increasing SP concentrations with the 300 MPa
      treatment. Thus, the addition of SP enhanced HP-induced denaturation of MHC and
      of a protein from MP of about 100 kDa.

PMID- 21074948
TI  - Influence of soiling on boar taint in boars.
AB  - It has been suggested that skatole, one of the main compounds responsible for
      boar taint, can be lowered by keeping pigs clean, as skatole can be absorbed
      through skin and/or lungs (Hansen, Larsen, Jensen, HansenMoller & Bartongade,
      1994). With this experiment, we further investigated this hypothesis by comparing
      extremely clean with extremely dirty animals with regard to the occurrence of
      boar taint. One group of boars was washed daily and pens were mucked on and
      littered down daily (CLEAN), a second group of boars was rubbed with faeces daily
      (DIRTY) and a third group of boars was kept in control conditions (CONTROL). The
      treatment was performed during the last four weeks before slaughter. According to
      the standardised consumer panel evaluations, boars subjected to extra soiling had
      a higher concentration of boar taint than boars that were kept extra clean. In
      contrast, expert panels judged general meat flavour to be inferior in CLEAN than
      CONTROL pigs. The home consumer panel, the hot iron method, and laboratory
      analyses, i.e., the presence of indole, skatole and androstenone in fat and
      serum, all showed no significant differences. So no clear indications towards
      skatole reduction by improving cleanliness of pigs were found.

PMID- 21074949
TI  - Application of pork fat diacylglycerols in meat emulsions.
AB  - The properties of fat are of major importance when meat products are produced. By
      enzymatic modification triacylglycerols (TAGs) can be converted to
      diacylglycerols (DAGs) resulting in changes of the physical and chemical
      properties of the fat. In this study the texture as well as the hydration and
      binding properties were investigated in meat emulsions prepared with lard
      substituted with different amounts of DAGs derived from the lard. In emulsions
      prepared with DAGs the percentage of total expressible fluid decreased from 28.2%
      in products prepared with lard to 11.8% in emulsions prepared with 100% DAGs. The
      fat separation decreased from 10.9% to 7.8% when 10% of DAGs were applied and no
      fat separation was observed for emulsions prepared with 50% and 100% DAGs.
      Emulsions containing DAGs were more elastic and solid reflected in a significant
      increase in Young's modulus and the maximum hardness. The results suggest future
      opportunities for the application of DAGs to improve the quality of meat
      products.

PMID- 21074950
TI  - Comment to "Desensitizing the posterior interosseous nerve alters wrist
      proprioceptive reflexes".

PMID- 21074951
TI  - What is our identity? What is our destiny?

PMID- 21074952
TI  - The use of surgical loupes in microsurgery.

PMID- 21074953
TI  - Basal joint osteoarthritis of the thumb: ligament reconstruction and tendon
      interposition versus hematoma distraction arthroplasty.
AB  - PURPOSE: Thumb basilar osteoarthritis is common. Several surgical options exist.
      Studies have evaluated outcomes in separate cohorts but have not compared
      methods. Our study compared the functional outcome of ligament reconstruction and
      tendon interposition (LRTI) suspension arthroplasty and hematoma distraction
      arthroplasty (HDA) by patient questionnaires, clinical measurements, and
      radiographic measurements to see whether there is validity in exclusively using
      either LRTI or HDA. METHODS: In this retrospective study, patients received LRTI
      (12 thumbs in 11 patients) or HDA (9 thumbs in 9 patients) according to the
      attending surgeon's preference, one exclusively performing LRTI and the other
      HDA. Patient perception was evaluated with a QuickDASH questionnaire and 10-point
      pain visual analog scale (VAS). Potential QuickDASH scores range from 0 to 100,
      with lower scores indicating better function. Clinical evaluation examined grip
      strength, tip pinch, and lateral pinch in kilograms-force, and range of motion.
      Measurements were compared with those from the contralateral hand and published
      normal values. Stressed and unstressed radiographs assessed metacarpal proximal
      and lateral migration and first web space. Chart review documented surgical
      times. RESULTS: The LRTI and HDA scored similarly on QuickDASH. Most reported
      excellent pain relief. Average grip, tip pinch, and lateral pinch were also
      similar in both groups. None achieved significance. Comparisons with
      contralateral hand and published normal results showed that LRTI and HDA were
      comparable. All except 2 could oppose to little finger base. With stress,
      additional proximal migration was similar. Web space was preserved with both
      procedures. LRTI took 54 minutes longer. CONCLUSIONS: The LRTI and HDA were
      comparable on all levels of objective and subjective measurements. Both groups
      satisfied the principal goals to provide a stable, mobile, pain-free thumb. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 21074954
TI  - Pseudarthrosis of cervical rib: an unusual cause of thoracic outlet syndrome.
AB  - Thoracic outlet syndrome is uncommon in adolescence. Cervical rib fracture is an
      extremely rare cause of thoracic outlet syndrome in this age group. We report an
      unusual case of thoracic outlet syndrome in a 14-year-old girl caused by
      pseudarthrosis of the cervical rib. A magnetic resonance imaging scan showed
      significant compression of the brachial plexus by the pseudarthrosis mass.
      Excision of the cervical rib through a supraclavicular approach gave excellent
      results in this case.

PMID- 21074955
TI  - Marine bacterial succession as a potential indicator of postmortem submersion
      interval.
AB  - The process of decomposition of bodies in the marine environment is poorly
      understood and almost nothing is currently known about the microorganisms
      involved. This study aimed to investigate the microbes involved in decomposition
      in the sea and to evaluate the potential use of marine bacterial succession for
      postmortem submersion interval (PMSI) estimation, for which there is currently no
      reliable method. Partial pig remains were completely submerged during autumn and
      winter and were regularly sampled to document marine bacterial colonisation and
      the changes in community composition over time. Five stages of decomposition were
      recognised, some of which exhibited characters specific for partial carrion.
      Marine bacteria rapidly colonised the submerged remains in a successional manner.
      Seasonal differences were observed for the rate of decomposition and also for
      several groups of colonising bacteria. Marine bacteria specific for particular
      PMSIs were identified. This study provides an insight into the involvement of
      saprophytic marine bacteria in the decomposition of mammalian remains in the sea
      and is the first to explore the use of marine bacterial colonisation and
      succession as a novel tool for PMSI estimation. We propose that with further
      study, marine bacterial succession will prove useful for determination of the
      length of time a body may have been immersed in a marine environment.

PMID- 21074956
TI  - A histological examination in the cases of initial diagnosis as chronic otitis
      media with a polypoid mass in the external ear canal.
AB  - OBJECTIVE: to analyse a large series of patients with initial diagnosis of
      chronic otitis media (COM) with a polypoid mass in the external ear canal (EAC).
      MATERIAL AND METHODS: 185 consecutive patients with COM were evaluated; 75 showed
      a polypoid mass in the EAC. RESULTS: In 65 out of the 75 (86.7%) patients,
      histological examination after mastoidectomy revealed cholesteatoma. In the
      remaining 10 (13.3%) cases, the histological diagnosis was: glomus tumor,
      melanoma, mucosal adenoma, fibrous dysplasia, squamous cell carcinoma, adenoma of
      the endolymphatic sac, encephalocele, and tuberculosis. One patient (glomus
      tumor) had undergone biopsy of the polypoid mass twice preoperatively and the
      initial histological diagnosis was "inflammatory polyp". Therefore, we examined
      the temporal bones with a glomus tumor diagnosis from the temporal bone
      collection of the House Ear Institute. In 1560 temporal bones, a glomus
      tympanicum was found in 6. In four cases, the tumor extended to the EAC mimicking
      a polyp covered by squamous epithelium. CONCLUSION: A significant percentage of
      polyps in COM may be the tip of an 'iceberg'. CT-scan and MRI techniques may be
      helpful but not always accurate, and biopsies have certain risks. Increased
      clinical suspicion may limit misdiagnosis and inappropriate management.

PMID- 21074957
TI  - Rud syndrome with focal cortical dysplasia: a case report.
AB  - We report a female patient with ichthyosis, epilepsy, mental retardation,
      hypergonadotrophic hypogonadism, polyneuropathy, and cranial dysmorphisms. This
      clinical picture may satisfy the main diagnostic criteria that characterize Rud
      syndrome (RS), a rare neurocutaneous disease. The patient underwent extensive
      clinical evaluation, neurophysiological studies (wakefulness and sleep EEG, EMG),
      dermatological and endocrinological evaluation and neuroimaging study (3 Tesla
      brain MRI). Interestingly, brain MRI unveiled a malformation of cortical
      development, never reported previously in RS. Although seizure semiology and EEG
      features could not provide clear cut information suggesting a focal onset, the
      role of this MRI finding in the genesis of the epileptic seizures cannot be ruled
      out. The finding of a focal cortical dysplasia in RS might be related to genetic
      abnormalities affecting the development of both epidermis and neural structures
      with the same embryological origin.

PMID- 21074958
TI  - Cerebrospinal fluid and serum levels of vitamin B6 in status epilepticus
      children.
AB  - Vitamin B6 (B6) is an essential cofactor of glutamate decarboxylase and catalyzes
      the decarboxylation of the excitatory neurotransmitter glutamate to the
      inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Although immediate
      administration of B6 to patients with acute encephalopathy with febrile
      convulsive status epilepticus (AEFCSE) is effective, it is not known whether
      prolonged seizures in status epilepticus (SE) children prevent the transport of
      B6 to the central nervous system (CNS) and/or induce the consumption of B6 inside
      the CNS. We evaluated the B6 concentration in cerebrospinal fluid (CSF) and serum
      in SE children. Further, we performed a sequential serum B6 analysis on days 1
      and 2 after admission and on the day before discharge. Among the several vitamers
      of B6, we used pyridoxal (PL) as a representative of B6 in this study. We
      enrolled 15 SE children (8 boys and 7 girls; age range,1-11years; average age,
      3.3years) and 21 control children (3 boys and 18 girls; age range, 7months
      14years; average age, 3.0years) and each group was divided into 2 subgroups
      according to age (4months-1year and 2-14years). We found no significant
      differences in the CSF PL levels, CSF/serum PL ratios, and serum PL levels in the
      SE and control subgroups. Our results suggest that prolonged seizures do not
      result in B6 deficiency in CSF and serum in SE children. Whenever necessary, B6
      should be administered to SE children with caution to prevent possible adverse
      effects.

PMID- 21074959
TI  - Capillary electrophoresis-based sirtuin assay using non-peptide substrates.
AB  - Sirtuins are NAD(+)-dependent class III histone deacetylases, which catalyze the
      deacetylation of acetyl-lysine residues of histones and other protein substrates
      yielding the deacetylated protein, nicotinamide and 2'-O-acetyl-ADP-ribose. Two
      lysine amide derivatives containing dansyl (Dns) or 7-dimethylaminocoumarin
      (DMAC) residues, i.e. Dns-K(Ac)-NH(2) and DMAC-K(Ac)-NH(2), were synthesized and
      evaluated as substrates for human sirtuin 1. A CZE method with field amplified
      sample injection and a MEKC method with sweeping were established and validated
      for monitoring the deacetylation process of Dns-K(Ac)-NH(2) and DMAC-K(Ac)-NH(2),
      respectively. Deacetylation by sirtuin 1 was demonstrated for both of the
      substrates. The Michaelis-Menten constants, K(m), were 88.0MUM for Dns-K(Ac)
      NH(2) and 42.9MUM for DMAC-K(Ac)-NH(2). The applicability of the methods was
      demonstrated using known sirtuin inhibitors. Resveratrol did not activate sirtuin
      1 using the present CE-based enzyme assay. The results indicated that the lysine
      derivatives can be used in sirtuin assays instead of peptide substrates.

PMID- 21074960
TI  - Fever and rigidity.

PMID- 21074961
TI  - Performances of sexuality counselling: a framework for provider-client
      encounters.
AB  - OBJECTIVE: Adequately assessing quality of care poses enormous challenges. While
      conducting fieldwork, we were struck by the need for a framework that
      encapsulates provider-client encounters. Little evidence exists concerning the
      most effective training, and management of health staff engaged in sexuality,
      reproductive health and HIV related health services. This paper proposes a
      framework for analysing these encounters. METHODS: This paper is based on five
      studies. Mixed method studies were carried out in Uganda and Kenya. Two
      additional studies looked into the effect of HIV on health worker performance in
      Uganda and Zambia. As a result of the findings, a desk review looked into factors
      affecting provider-client encounters in order to improve the responsiveness of
      programs. RESULTS: Positive encounters between provider and client are built on
      trust and respect, consist of communication, practice and process, and are
      influenced by space, place and context. Combining these facets allows for a
      better understanding of their interactions. CONCLUSION: A holistic perspective in
      which the breadth of dynamics and processes are described should be used when
      assessing the quality of provider-client encounters. PRACTICE IMPLICATIONS:
      Within training, management and human resource planning, these dynamics need to
      be utilized to realize the best possible care.

PMID- 21074962
TI  - Do improvements in client-provider interaction increase contraceptive
      continuation? Unraveling the puzzle.
AB  - OBJECTIVE: Evidence on the association between client-provider interaction (CPI)
      and contraceptive continuation has been mixed. This paper attempts to unravel the
      puzzle by examining various factors that may have contributed to the mixed
      results. METHODS: This paper critically reviews key studies that examined the
      association between CPI and contraceptive continuation. A scan of peer reviewed
      publications and project reports was undertaken with a focus on CPI and
      contraceptive continuation. In addition, a review of key studies that examined
      the impact of interventions to improve CPI in compliance with medical regimens
      was carried out. RESULTS: The inconsistency of results may be attributed to
      methodological factors, characteristics of interventions to improve CPI, or
      conceptual factors related to the complexity of the issue of contraceptive
      continuation. CONCLUSION: More rigorous research is needed to understand the role
      played by CPI in contraceptive continuation as well as socio-demographic,
      behavioral and contextual factors that moderate the relationship between CPI and
      contraceptive continuation. PRACTICE IMPLICATIONS: Counseling services should be
      expanded to address physical, social and emotional needs of continuing clients.
      Moreover, interventions to improve CPI should also address contextual and health
      system factors that prevent clients from using family planning consistently and
      effectively.

PMID- 21074963
TI  - Perceptions of care coordination in a population-based sample of diverse breast
      cancer patients.
AB  - OBJECTIVE: To identify factors associated with perceptions of care coordination
      in a diverse sample of breast cancer patients. METHODS: Breast cancer patients
      reported to the metropolitan SEER registries of Detroit or Los Angeles from 6/05
      to 2/07 were surveyed after diagnosis (N=2268, RR=72.4%). Outcomes were two
      dichotomous measures reflecting patient appraisal of care coordination during
      their treatment experience. Primary independent variables were race/ethnicity
      (white, African American, Latina-high acculturated, Latina-low acculturated) and
      health literacy (low, moderate, high). Logistic regression was used to evaluate
      factors associated with both measures of care coordination. RESULTS: 2148
      subjects were included in the analytic dataset. 16.4% of women perceived low care
      coordination and 12.5% reported low satisfaction. Race/ethnicity was not
      significantly associated with care coordination. Women with low subjective health
      literacy were 3-4 times as likely as those with high health literacy to perceive
      low care coordination and low satisfaction with care coordination (OR=3.88; 95%
      CI: 2.78-5.41; OR=3.19 95% CI: 2.25-4.52, respectively). CONCLUSIONS: Many breast
      cancer patients positively appraised their care coordination, but patients with
      low health literacy perceived low care coordination. PRACTICE IMPLICATIONS:
      Providers should be aware of the health literacy deficits that may contribute to
      their patients' attitudes towards their breast cancer care coordination.

PMID- 21074964
TI  - Comparison of the reliability, responsiveness, and construct validity of 4
      different questionnaires for evaluating outcomes after total knee arthroplasty.
AB  - The study aimed to compare the reliability, responsiveness and construct
      convergent validity of four questionnaires (Western Ontario and McMaster
      Universities Osteoarthritis Index, Activities of Daily Living of the Knee Outcome
      Survey, Oxford Knee Score, and the 12-item Short Form Health Survey) in total
      knee arthroplasty patients. Seventy-nine patients completed the questionnaires
      before surgery and 6 months later. The reliability was high for all instruments
      with intraclass correlation coefficients from 0.81 to 0.96 and SEMs from 6.6% to
      28.3% of mean scores. The score changes after surgery were three- to five-fold
      the instruments' measurement error. The responsiveness was large for all
      instruments. In conclusion most of the selected instruments were reliable and
      responsive. It was not possible to clearly identify a "best" or "better" tool and
      hence all can be considered useful, with the reported psychometric properties
      serving to guide the choice of instrument for a given purpose.

PMID- 21074966
TI  - Dyssynchrony in obese subjects without a history of cardiac disease using
      velocity vector imaging.
AB  - BACKGROUND: The aim of this study was to examine the occurrence of intra-left
      ventricular (LV) dyssynchrony in obese versus nonobese subjects without known
      cardiac disease using Velocity Vector Imaging (VVI). METHODS: One hundred ninety
      consecutive subjects with no known cardiac disease had their echocardiograms
      analyzed using VVI after excluding subjects with QRS durations>120 msec or LV
      ejection fractions<55%. Study subjects were divided into two groups on the basis
      of body mass index: obese (>30 kg/m2) and nonobese (<30 kg/m2). RESULTS: The
      final cohort included 136 subjects (74 obese; 32% women; mean age, 55+/-16
      years). The occurrence of intra-LV dyssynchrony was higher in the obese group
      compared with the nonobese group. CONCLUSIONS: There was an increased prevalence
      of intra-LV dyssynchrony in obese subjects, especially longitudinal and radial
      dyssynchrony. This dyssynchrony may signal a mechanism by which obesity
      predisposes to the development of heart failure.

PMID- 21074965
TI  - New equations and a critical appraisal of coronary artery Z scores in healthy
      children.
AB  - BACKGROUND: The aim of this study was to find the best model to obtain valid and
      normally distributed Z scores for coronary artery (CA) diameters in a large,
      heterogeneous population of healthy children. METHODS: Echocardiography was
      performed on 1,033 healthy children. Several regression models were tested with
      height, weight, body surface area, and aortic valve diameter. The computed Z
      scores were tested for normal distribution and stability. RESULTS: CA diameter
      was best predicted using regression with the square root of body surface area.
      The weighted least squares method yielded normally distributed and very stable Z
      score estimates for all CA segments. In prepubertal children, aortic valve
      diameter was also a valid predictor of CA diameter. CONCLUSIONS: This study shows
      two valid methods to estimate Z scores for CA size in children of all ages. Such
      Z scores are important for risk stratification in patients with Kawasaki disease.

PMID- 21074967
TI  - A triple combination strategy corrects population stratification bias and saves
      genotyping cost.
AB  - OBJECTIVE: The case-control association study has gained popularity for mapping
      disease-susceptibility gene(s) of complex human diseases. However, the study is
      prone to population stratification bias. STUDY DESIGN AND SETTING: The authors
      proposed a triple combination strategy of stratum matching, genomic control, and
      multiple DNA pooling for population-based case-control association studies. Monte
      Carlo simulation showed that the type I error rates are well controlled using
      this strategy. RESULTS: As for power, it increases under the following
      situations: (1) more accurate stratum matching, (2) more null markers for genomic
      control, (3) more DNA pooling sets, and (4) more accurate DNA pooling
      measurement. CONCLUSION: The triple combination strategy corrects population
      stratification bias and saves genotyping cost.

PMID- 21074968
TI  - Recruitment of newly diagnosed ovarian cancer patients proved challenging in a
      multicentre biobanking study.
AB  - OBJECTIVE: To explore the challenges of recruiting ovarian cancer patients and
      healthy controls to a cancer biobanking study. STUDY DESIGN AND SETTING: The
      study was set up in gynecological cancer centers in 10 National Health Service
      trusts across the United Kingdom. Women were approached if they were undergoing
      investigations/awaiting treatment for ovarian cancer, had a previous diagnosis of
      ovarian cancer, or were attending for annual screening in an ovarian cancer
      screening trial. Those who consented completed a detailed epidemiologic
      questionnaire, provided blood and tissue samples if appropriate. RESULTS: The
      overall proportion of those recruited compared with the expected targets was
      76.4% for healthy controls, 86.0% for old cases, and 46.9% for new cases. Only 4
      of 10 (40%) centers recruited over 50% of their target for new cases.
      Unwillingness to participate was reported as primarily because of patients being
      too unwell, wanting to focus only on their treatment, or having insufficient time
      because of conflicting medical appointments. Concerns about use of personal data
      or tissue and blood samples for genetic research and lack of direct benefit were
      reported as significant challenges to recruitment. CONCLUSION: When setting
      recruitment targets for patients undergoing investigations or awaiting treatment
      for cancer (new cases), it is important to consider lower response rates because
      of various patient, logistical, and trial-specific challenges.

PMID- 21074969
TI  - Variability in measuring (instrumental) activities of daily living functioning
      and functional decline in hospitalized older medical patients: a systematic
      review.
AB  - OBJECTIVE: To study instruments used and definitions applied in order to measure
      (instrumental) activities of daily living (I [ADL]) functioning and functional
      decline in hospitalized older medical patients. STUDY DESIGN: We systematically
      searched Medline, Embase, and the Cochrane Database of Systematic Reviews from
      1990 to January 2010. Articles were included if they (1) focused on acute
      hospitalization for medical illness in older patients; (2) described the
      instrument used to measure functioning; and (3) outlined the clinical definition
      of functional decline. Two reviewers independently extracted data. RESULTS: In
      total, 28 studies were included in this review. Five different instruments were
      used to measure functioning: the Katz ADL index, the IADL scale of Lawton and
      Brody, the Barthel index, Functional Independence Measure, and Care Needs
      Assessment. Item content and scoring between and within the instruments varied
      widely. The minimal amount for decline, as defined by the authors, referred to a
      decrease in functioning between 2.4% and 20.0%. CONCLUSION: This review shows
      there is a large variability in measuring (I)ADL functioning of older
      hospitalized patients and a large range of clinical definitions of functional
      decline. These conceptual and clinimetric barriers hamper the interpretation and
      comparison of functional outcome data of epidemiological and clinical studies.

PMID- 21074971
TI  - Concentric decile segmentation of white and hypopigmented areas in dermoscopy
      images of skin lesions allows discrimination of malignant melanoma.
AB  - Dermoscopy, also known as dermatoscopy or epiluminescence microscopy (ELM),
      permits visualization of features of pigmented melanocytic neoplasms that are not
      discernable by examination with the naked eye. White areas, prominent in early
      malignant melanoma and melanoma in situ, contribute to early detection of these
      lesions. An adaptive detection method has been investigated to identify white and
      hypopigmented areas based on lesion histogram statistics. Using the Euclidean
      distance transform, the lesion is segmented in concentric deciles. Overlays of
      the white areas on the lesion deciles are determined. Calculated features of
      automatically detected white areas include lesion decile ratios, normalized
      number of white areas, absolute and relative size of largest white area, relative
      size of all white areas, and white area eccentricity, dispersion, and
      irregularity. Using a back-propagation neural network, the white area statistics
      yield over 95% diagnostic accuracy of melanomas from benign nevi. White and
      hypopigmented areas in melanomas tend to be central or paracentral. The four most
      powerful features on multivariate analysis are lesion decile ratios. Automatic
      detection of white and hypopigmented areas in melanoma can be accomplished using
      lesion statistics. A neural network can achieve good discrimination of melanomas
      from benign nevi using these areas. Lesion decile ratios are useful white area
      features.

PMID- 21074972
TI  - Zinc restriction during different periods of life: influence in renal and
      cardiovascular diseases.
AB  - Micronutrient undernutrition during critical periods of growth has become an
      important health issue in developing and developed countries, particularly among
      pregnant women and children having an imbalanced diet. Zinc is a widely studied
      microelement in infant feeding because it is a component of several enzymes
      involved in intermediary metabolism ranging from growth to cell differentiation
      and metabolism of proteins, carbohydrates, and lipids. Human and experimental
      studies have reported an association between zinc deficiency and the
      etiopathogenesis of cardiovascular and renal diseases like hypertension,
      atherosclerosis, congestive heart failure, coronary heart disease, and diabetes.
      The main links between the development of these pathologies and zinc deficiency
      are multiple mechanisms involving oxidative stress damage, apoptosis, and
      inflammation. A substantial body of evidence suggests that a poor in utero
      environment elicited by maternal dietary or placental insufficiency may
      "programme" susceptibility in the fetus to later development of cardiovascular,
      renal, metabolic, and endocrine diseases. Zinc deficiency in rats during
      intrauterine and postnatal growth can also be considered a model of fetal
      programming of cardiovascular and renal diseases in adult life. Dietary zinc
      restriction during fetal life, lactation, and/or postweaning induces an increase
      in arterial blood pressure and impairs renal function in adult life. This review
      focuses on the contributions of experimental and clinical studies to current
      knowledge of the physiologic role of zinc in the cardiovascular and renal
      systems. Moreover, this review examines the relationship between zinc deficiency
      during different periods of life and the development of cardiovascular and renal
      diseases in adult life.

PMID- 21074973
TI  - The cost of a healthy diet: a South African perspective.
AB  - Energy-dense foods are relatively cheap sources of energy but typically have a
      low nutrient density. People with a low income may therefore select a relatively
      less healthy diet. The high energy density of such diets helps explain the
      association between obesity and low socioeconomic status. Most studies have been
      carried out in highly developed countries. We have extended this research to
      South Africa. Some foods, such as oats, beans, carrots, and apples, are
      moderately priced sources of energy and are healthy (i.e., they have a low energy
      density and are nutrient dense). However, such foods are likely to be less
      desired than many other foods, such as candy, cookies, jam, and chocolate, that
      have a similar cost (in terms of food energy) but are less healthy. We compared
      the cost of a typical South African diet with a healthier one. On average, the
      healthier diet costs 69% more, but this estimate is greatly affected by food
      choices. For a family whose household income is exceeded by one-third of the
      population, this increased expenditure represents about 30% of total household
      income. This could be decreased to about 10% to 15% if a healthy diet is
      carefully designed. Overall, a healthy diet is unaffordable for most South
      Africans. This shows the importance of not only educating people in developing
      countries to the importance of a healthy diet but also explaining how to make
      such a diet affordable. A more effective strategy is government intervention that
      manipulates food prices.

PMID- 21074974
TI  - A randomized controlled trial of cognitive behavioral therapy for individuals at
      clinical high risk of psychosis.
AB  - BACKGROUND: There has been increasing interest in early detection during the
      prodromal phase of a psychotic disorder. To date a few treatment studies have
      been published with some promising results for both pharmacological treatments,
      using second generation antipsychotics, and psychological interventions, mainly
      cognitive behavioral therapy. The purpose of this study was to determine first if
      cognitive behavioral therapy (CBT) was more effective in reducing the rates of
      conversion compared to a supportive therapy and secondly whether those who
      received CBT had improved symptoms compared to those who received supportive
      therapy. METHOD: Fifty-one individuals at clinical high risk of developing
      psychosis were randomized to CBT or a supportive therapy for up to 6 months. The
      sample was assessed at 6, 12 and 18 months post baseline on attenuated positive
      symptoms, negative symptoms, depression, anxiety and social functioning. RESULTS:
      Conversions to psychosis only occurred in the group who received supportive
      therapy although the difference was not significant. Both groups improved in
      attenuated positive symptoms, depression and anxiety and neither improved in
      social functioning and negative symptoms. There were no differences between the
      two treatment groups. However, the improvement in attenuated positive symptoms
      was more rapid for the CBT group. CONCLUSIONS: There are limitations of this
      trial and potential explanations for the lack of differences. However, both the
      results of this study and the possible explanations have significant implications
      for early detection and intervention in the pre-psychotic phase and for designing
      future treatments.

PMID- 21074975
TI  - Ultra high risk (UHR) for psychosis criteria: are there different levels of risk
      for transition to psychosis?
AB  - INTRODUCTION: The ultra high risk (UHR) for psychosis criteria have been
      validated in a number of studies. However, it is not known whether particular UHR
      criteria (Attenuated Psychotic Symptoms (APS), Brief Limited Intermittent
      Psychotic Symptoms (BLIPS) or Trait vulnerability criteria), or combination of
      criteria, is associated with a higher risk of transition to psychosis. The
      current study investigated this issue over a 6-month follow-up period. We
      hypothesised that the risk of transition would increase in the following order:
      Trait alone<APS alone < APS+Trait<BLIPS. METHOD: Data on UHR intake criteria and
      transition to psychosis status at 6 months were analysed for UHR patients seen at
      the PACE clinic, Orygen Youth Health between January 2000 and November 2008.
      RESULTS: A total of 928 new referrals were accepted into the PACE clinic over
      this period of whom 817 (88%) had baseline information available for analysis.
      The percentage of subjects who presented with APS, Trait and BLIPS were 83%, 27%
      and 4%, respectively. When the two intermediate groups (APS alone and APS+Trait)
      were combined, there was evidence that the risk of transition increased in the
      order of Trait alone<APS<BLIPS (p=0.024, adjusted analysis). CONCLUSIONS: Our
      data suggest that UHR intake criteria predict transition over 6 months in the
      order of Trait alone<APS<BLIPS. The fact that BLIPS patients are at the highest
      risk of transition over the short term is consistent with the "early" versus
      "late" prodrome model. It also indicates that particular clinical attention may
      need to be paid to BLIPS patients, especially early in the course of treatment.

PMID- 21074976
TI  - Relation between the expression levels of the POU transcription factors Skn-1a
      and Skn-1n and keratinocyte differentiation.

PMID- 21074977
TI  - Raf kinase inhibitor protein expression correlates with differentiation but not
      with ERK phosphorylation in cutaneous squamous cell carcinoma.

PMID- 21074978
TI  - Classification of melanomas in situ using knowledge discovery with explained case
      based reasoning.
AB  - OBJECTIVE: Early diagnosis of melanoma is based on the ABCD rule which considers
      asymmetry, border irregularity, color variegation, and a diameter larger than 5mm
      as the characteristic features of melanomas. When a skin lesion presents these
      features it is excised as prevention. Using a non-invasive technique called
      dermoscopy, dermatologists can give a more accurate evaluation of skin lesions,
      and can therefore avoid the excision of lesions that are benign. However,
      dermatologists need to achieve a good dermatoscopic classification of lesions
      prior to extraction. In this paper we propose a procedure called LazyCL to
      support dermatologists in assessing the classification of skin lesions. Our goal
      is to use LazyCL for generating a domain theory to classify melanomas in situ.
      METHODS: To generate a domain theory, the LazyCL procedure uses a combination of
      two artificial intelligence techniques: case-based reasoning and clustering.
      First LazyCL randomly creates clusters and then uses a lazy learning method
      called lazy induction of descriptions (LID) with leave-one-out on them. By means
      of LID, LazyCL collects explanations of why the cases in the database should
      belong to a class. Then the analysis of relationships among explanations produces
      an understandable clustering of the dataset. After a process of elimination of
      redundancies and merging of clusters, the set of explanations is reduced to a
      subset of it describing classes that are "almost" discriminant. The remaining
      explanations form a preliminary domain theory that is the basis on which experts
      can perform knowledge discovery. RESULTS: We performed two kinds of experiments.
      First ones consisted on using LazyCL on a database containing the description of
      76 melanomas. The domain theory obtained from these experiments was compared on
      previous experiments performed using a different clustering method called self
      organizing maps (SOM). Results of both methods, LazyCL and SOM, were similar. The
      second kind of experiments consisted on using LazyCL on well known domains coming
      from the machine learning repository of the Irvine University. Thus, since these
      domains have known solution classes, we can prove that the clusters build by
      LazyCL are correct. CONCLUSIONS: We can conclude that LazyCL that uses explained
      case-based reasoning for knowledge discovery is feasible for constructing a
      domain theory. On one hand, experiments on the melanoma database show that the
      domain theory build by LazyCL is easy to understand. Explanations provided by LID
      are easily understood by domain experts since these descriptions involve the same
      attributes than they used to represent domain objects. On the other hand,
      experiments on standard machine learning data sets show that LazyCL is a good
      method of clustering since all clusters produced are correct.

PMID- 21074979
TI  - Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in
      rat.
AB  - The present study was carried out to evaluate the antioxidant effect of the
      chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves
      in Sprague-Dawley male rats. The different groups of animals were administered
      with carbon tetrachloride (CCl(4); 20% in olive oil, 2 ml/kg body weight) 7 doses
      (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin
      at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl(4)
      treated rats. The effect of CSCE or silymarin on urine and serum markers (urea,
      creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was
      measured in CCl(4)-induced nephrotoxicity in rat. Further, the effects on lipid
      peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase,
      glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non
      enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The
      CSCE and silymarin produced significant renal protective effects by restoring the
      concentration of urine and serum markers. Activity level of antioxidant enzymes
      and GSH contents were increased while lipid peroxidation (TBARS) was decreased,
      dose dependently with CSCE and silymarin. Decrease in body whereas increase in
      kidney weight induced with CCl(4) was restored with CSCE and silymarin. Chemical
      composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids
      and very low amount of saponins. Total flavonoids estimated were (127 +/- 14.6)
      as rutin equivalent mg/g of the extract. From these results, it is suggested that
      CSCE possesses potent nephroprotective and antioxidant properties.

PMID- 21074980
TI  - Receptor mobility, the cytoskeleton, and particle binding during phagocytosis.
AB  - Particle engulfment during phagocytosis has long been appreciated to be an
      active, actin-driven process. By contrast, the preceding stage--securing the
      target to the surface of the phagocyte--was thought to result from the passive
      diffusion of receptors along the membrane towards their ligands on the particle
      surface. Recent evidence, however, challenges this notion, demonstrating that
      receptors do not diffuse freely along the phagocyte surface and that actin
      polymerization and tyrosine phosphorylation are required for optimal particle
      binding. The interpretation and significance of these observations are the
      subject of this opinion piece.

PMID- 21074981
TI  - Can soil gas profiles be used to assess microbial CH4 oxidation in landfill
      covers?
AB  - A method is proposed to estimate CH(4) oxidation efficiency in landfill covers,
      biowindows or biofilters from soil gas profile data. The approach assumes that
      the shift in the ratio of CO(2) to CH(4) in the gas profile, compared to the
      ratio in the raw landfill gas, is a result of the oxidation process and thus
      allows the calculation of the cumulative share of CH(4) oxidized up to a
      particular depth. The approach was validated using mass balance data from two
      independent laboratory column experiments. Values corresponded well over a wide
      range of oxidation efficiencies from less than 10% to nearly total oxidation. An
      incubation experiment on 40 samples from the cover soil of an old landfill showed
      that the share of CO(2) from respiration falls below 10% of the total CO(2)
      production when the methane oxidation capacity is 3.8 MUg CH(4)g(dw)(-1)h(-1) or
      higher, a rate that is often exceeded in landfill covers and biofilters. The
      method is mainly suitable in settings where the CO(2) concentrations are not
      significantly influenced by processes such as respiration or where CH(4) loadings
      and oxidation rates are high enough so that CO(2) generated from CH(4) oxidation
      outweighs other sources of CO(2). The latter can be expected for most biofilters,
      biowindows and biocovers on landfills. This simple method constitutes an
      inexpensive complementary tool for studies that require an estimation of the
      CH(4) oxidation efficiency values in methane oxidation systems, such as landfill
      biocovers and biowindows.

PMID- 21074982
TI  - Temporal variability of soil gas composition in landfill covers.
AB  - In order to assess the temporal variability of the conditions for the microbial
      oxidation of methane in landfill cover soils and their driving variables, gas
      composition at non-emissive and strongly emissive locations (hotspots) was
      monitored on a seasonal, daily and hourly time scale on an old, unlined landfill
      in northern Germany. Our study showed that the impact of the various
      environmental factors varied with the mode of gas transport and with the time
      scale considered. At non-emissive sites, governed by diffusive gas transport,
      soil gas composition was subject to a pronounced seasonal variation. A high
      extent of aeration, low methane concentrations and a high ratio of CO(2) to CH(4)
      were found across the entire depth of the soil cover during the warm and dry
      period, whereas in the cool and moist period aeration was less and landfill gas
      migrated further upward. Statistically, variation in soil gas composition was
      best explained by the variation in soil temperature. At locations dominated by
      advective gas transport and showing considerable emissions of methane, this
      pattern was far less pronounced with only little increase in the extent of
      aeration during drier periods. Here, the change of barometric pressure was found
      to impact soil gas composition. On a daily scale under constant conditions of
      temperature, gas transport at both types of locations was strongly impacted by
      the change in soil moisture. On an hourly scale, under constant conditions of
      temperature and moisture, gas migration was impacted most by the change in
      barometric pressure. It was shown that at diffusion-dominated sites complete
      methane oxidation was achieved even under adverse wintry conditions, whereas at
      hotspots, even under favorable dry and warm conditions, aerobic biological
      activity can be limited to the upper crust of the soil.

PMID- 21074983
TI  - Soil bioassays as tools for sludge compost quality assessment.
AB  - Composting is a waste management technology that is becoming more widespread as a
      response to the increasing production of sewage sludge and the pressure for its
      reuse in soil. In this study, different bioassays (plant germination, earthworm
      survival, biomass and reproduction, and collembolan survival and reproduction)
      were assessed for their usefulness in the compost quality assessment. Compost
      samples, from two different composting plants, were taken along the composting
      process, which were characterized and submitted to bioassays (plant germination
      and collembolan and earthworm performance). Results from our study indicate that
      the noxious effects of some of the compost samples observed in bioassays are
      related to the low organic matter stability of composts and the enhanced release
      of decomposition endproducts, with the exception of earthworms, which are
      favored. Plant germination and collembolan reproduction inhibition was generally
      associated with uncomposted sludge, while earthworm total biomass and
      reproduction were enhanced by these materials. On the other hand, earthworm and
      collembolan survival were unaffected by the degree of composting of the wastes.
      However, this pattern was clear in one of the composting procedures assessed, but
      less in the other, where the release of decomposition endproducts was lower due
      to its higher stability, indicating the sensitivity and usefulness of bioassays
      for the quality assessment of composts.

PMID- 21074984
TI  - Leaching characteristics of bottom ash from coal fired electric generating
      plants, and waste tire; individually and mixtures when used as construction site
      fill materials.
AB  - Column leaching tests were conducted on bottom ash from coal fired electric
      generating plants, waste tires (WT), and bottom ash mixtures (ash-WT) to evaluate
      the environmental feasibility of using these materials as fill materials to raise
      the ground level at construction sites. The initial concentrations of As, Cd, Cr,
      Cu, Hg, F(-), NO(2)(-), NO(3)(-), and PO(4)(2-) from ash, WT, and ash-WT samples
      were lower than the drinking water standards (DWSs). The initial concentrations
      of Pb and Zn were slightly above the standards but within the DWS approximately
      one pore volume of effluent (PVE). However, the initial concentrations of SO(4)(2
      ) from ash and ash-WT were 8-10 times greater than the standards and a maximum
      8.21 PVE was required to meet the DWS. In general, the ash-WT combinations
      resulted in lower initial concentrations but greater partition coefficients for
      Pb and Zn than those for ash alone. These results suggest precautions are needed
      before using bottom ash as a fill material at construction sites because of the
      high SO(4)(2-) levels.

PMID- 21074985
TI  - One-pot synthesis of fluorescent oligonucleotide Ag nanoclusters for specific and
      sensitive detection of DNA.
AB  - In this study, we prepared fluorescent, functional oligonucleotide-stabilized
      silver nanoclusters (FFDNA-Ag NCs) through one-pot synthesis and then employed
      them as probes for single nucleotide polymorphisms (SNPs). The FFDNA-Ag NCs were
      obtained through the NaBH(4)-mediated reduction of AgNO(3) in the presence of a
      DNA strand having the sequence 5'-C(12)-CCAGATACTCACCGG-3'. The specific DNA
      scaffold combines a fluorescent base motif (C(12)) and a specific sequence
      (CCAGATACTCACCGG) that recognizes a gene for fumarylacetoacetate hydrolase (FAH).
      The sensing mechanism of our new probe is based on the FFDNA-Ag NCs having
      different stabilities (fluorescence intensities) in solutions containing 150 mM
      NaCl in the absence and presence of perfect match DNA (DNA(pmt)). Under the
      optimal conditions (150 mM NaCl, 20 mM phosphate solution, pH 7.0), the
      fluorescence ratios of the FFDNA-Ag NC probes in the presence and absence of
      DNA(pmt), plotted against the concentration of DNA(pmt), was linear over the
      range 25-1000 nM (R(2)=0.98), with a limit of detection (S/N=3) of 14 nM. This
      cost-effective and simple FFDNA-Ag NC probe is sensitive and selective for SNPs
      of a gene for FAH.

PMID- 21074986
TI  - The effect of socks on vertical and anteroposterior ground reaction forces in
      walking and running.
AB  - BACKGROUND: Previous research suggests that socks may have the potential for
      injury protection through the absorption and/or redistribution of impact forces.
      However, there is limited research regarding the shock attenuation qualities of
      athletic socks in sporting populations and previously observed pressure
      reductions have not been quantified using a force plate. OBJECTIVE: Firstly to
      identify the effect of specialist athletic socks on vertical and anteroposterior
      ground reaction forces (GRFs) during walking and running. Secondly, to compare
      GRFs between specialist socks, non-specialist socks and barefoot walking and
      running conditions. METHODS: Following ethical approval participants (n=5)
      completed five walking (1.52-1.68 m s(-1)) and running (3.8-4.2 m s(-1)) trials,
      unshod, over a force plate. This was completed before and after a 5000 m run (3.2
      m s(-1)) in their own trainers in three conditions; barefoot, non-specialist
      socks and specialist running socks. RESULTS: Significant differences were
      identified between barefoot and specialist sock conditions for pre-intervention
      time to impact peak (F=3.110((2)), P=.05, r=.11) and maximum propulsive force
      (F=8.126((2)), P=.001, r=.25) when walking. Post hoc analysis identified an
      increase of .0016 s in time to impact peak when walking barefoot compared to the
      specialist sock condition (T=-7.402((4)), P=.002, r=.71). During walking the
      specialist sock also demonstrated a significant decrease of .075 BWs in maximum
      propulsive force when compared to the barefoot condition (T=-7.624((4)), P=.002,
      r=.79). Both significant effects diminished following the 5000 m run. CONCLUSION:
      Findings suggest that the specialist running sock has limited effects on GRFs and
      therefore may be responsible for a limited degree of shock attenuation
      experienced during walking.

PMID- 21074987
TI  - Hypoxia and energetic tumour metabolism.
AB  - The hypoxia-inducible factor (HIF-1), in addition to genetic and epigenetic
      changes, is largely responsible for alterations in cell metabolism in hypoxic
      tumour cells. This transcription factor not only favours cell proliferation
      through the metabolic shift from oxidative phosphorylation to glycolysis and
      lactic acid production but also stimulates nutrient supply by mediating adaptive
      survival mechanisms. These include epithelial-mesenchymal transition,
      angiogenesis, autophagy, and synthesis and storage of lipid and glycogen. HIF-1
      also ensures survival by correcting tumour acidosis via increased expression of
      the carbonic anhydrase CA IX and the lactate/H+ symporter MCT4. The targeting of
      key HIF-1-mediated steps, responsible for exacerbated glycolysis and pHi-control,
      and of the 'guardian of cellular energy' AMP-kinase should offer novel
      therapeutic opportunities to fight cancer.

PMID- 21074988
TI  - The maturation of cortical interneuron diversity: how multiple developmental
      journeys shape the emergence of proper network function.
AB  - If the classical functional attribute of cortical GABAergic interneurons is to
      mediate synaptic inhibition in the adult cortex, it is becoming evident that
      their major task is instead to shape the spatio-temporal dynamics of the network
      oscillations that support most brain functions. This complex function involves a
      division of labour between morpho-physiologically diverse interneuron subtypes.
      Both the central network function and the bewildering heterogeneity of the
      interneuron population are especially emphasized during cortical development: at
      early postnatal stages, a single GABAergic neuron can efficiently pace the
      activity of hundreds of other cells, whereas some interneuron subtypes are still
      poorly developed. Given the role of coherent activity in brain development, this
      confers to GABAergic interneurons a major role in the proper maturation of
      cortical networks.

PMID- 21074989
TI  - Six-month postoperative quality of life predicts long-term survival after
      oesophageal cancer surgery.
AB  - BACKGROUND: Patients treated with curatively intended surgery for oesophageal
      cancer have an approximately 30% chance of 5-year survival. Little is known about
      associations between postoperative health-related quality of life (HRQL) and long
      term survival. HYPOTHESIS: Poor postoperative HRQL after curatively intended
      oesophageal cancer surgery is associated with a reduced long-term survival.
      METHODS: A Swedish nationwide cohort of oesophageal cancer patients, treated
      surgically between 2001 and 2005, was followed up until death or end of August
      2009. Nine HRQL aspects were selected for analyses from EORTC QLQ-C30 and QLQ
      OES18 questionnaires answered 6 months postoperatively. The HRQL measures were
      categorised into two groups: 'good function' versus 'poor function' and 'no or
      minor symptoms' versus 'symptomatic'. Associations between HRQL and survival were
      analysed using Cox proportional hazard ratios (HR) and 95% confidence intervals
      (CIs), adjusted for potential confounding factors. FINDINGS: All 401 oesophageal
      cancer patients who survived at least 6 months postoperatively and responded to
      the questionnaires were included. For each of the nine selected outcomes, poor
      scores were associated with an increased hazard ratio of mortality: global HRQL
      (HR=1.55; 95% CI 1.19-2:02), physical function (HR=1.56; 95% CI 1.23-1.99),
      social function (HR=1.52; 95% CI 1.19-1.94), fatigue (HR=1.65; 95% CI 1.30-2.11),
      pain (HR=1.45; 95% CI 1.22-1.87), dyspnoea (HR=1.54; 95% CI 1.19-2.01), appetite
      loss (HR=1.69; 95% CI 1.32-2.14), dysphagia (HR=1.69; 95% CI 1.13-2.51) and
      oesophageal pain (HR=1.29; 95% CI 1.02-1.65). INTERPRETATIONS: HRQL assessed 6
      months after oesophageal cancer surgery can be used as a clinically useful
      prognostic factor.

PMID- 21074990
TI  - Characterization of multiple chlorobenzoic acid-degrading organisms from pristine
      and contaminated systems: mineralization of 2,4-dichlorobenzoic acid.
AB  - Multiple bacterial strains with CBA metabolic properties were isolated using a
      simple selective strategy. Phylogenetic analysis of the 16S rRNA gene sequences
      grouped them into two main clusters consisting of four bacterial phyla and
      belonging to 17 genera. Whereas growth was more frequent with 2-CBA (~68%), 50%
      grew on 4-CBA and ~7% utilized 3-CBA. One third of the strains exhibited 2,4
      dichlorobenzoic acid (2,4-diCBA) catabolic function and were mainly
      representatives of alpha-, beta- and gamma-Proteobacteria. In batch experiments,
      growth was concomitant with substrate disappearance and near-stoichiometric
      release of chloride. Doubling times for 2,4-diCBA degradation doubled those
      determined for mono-substituted CBAs. Out of the six 2,4-diCBA degraders
      submitted for enzyme assays, significant induction of catechol 1,2-dioxygenase
      types I and II activities in cell-free extracts were found in four while
      protocatechuate 3,4-dioxygenase activity was detected in the remaining two.
      Activities in CBA-grown cells were 20 orders-of-magnitude higher than those grown
      on benzoic acid.

PMID- 21074991
TI  - Biological activity and preclinical efficacy of azetidinyl pyridazines as potent
      systemically-distributed stearoyl-CoA desaturase inhibitors.
AB  - Potent and orally bioavailable SCD inhibitors built on an azetidinyl pyridazine
      scaffold were identified. In a one-month gDIO mouse model of obesity, we
      demonstrated that there was no therapeutic index even at low doses; efficacy in
      preventing weight gain tracked closely with skin and eye adverse events. This was
      attributed to the local SCD inhibition in these tissues as a consequence of the
      broad tissue distribution observed in mice for this class of compounds. The
      search for new structural scaffolds which may display a different tissue
      distribution was initiated. In preparation for an HTS campaign, a radiolabeled
      azetidinyl pyridazine displaying low non-specific binding in the scintillation
      proximity assay was prepared.

PMID- 21074992
TI  - A novel series of IKKbeta inhibitors part II: description of a potent and
      pharmacologically active series of analogs.
AB  - A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene)
      thiosemicarbazides was discovered as potent inhibitors of IKKbeta. In this Letter
      we document our efforts at further optimization of this series, culminating in 2
      with submicromolar potency in a HWB assay and efficacy in a CIA mouse model.

PMID- 21074993
TI  - A novel series of IKKbeta inhibitors part I: Initial SAR studies of a HTS hit.
AB  - A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene)
      thiosemicarbazides was discovered as potent inhibitors of IKKbeta. In this Letter
      we document our early efforts at optimization of the quinoline core, the
      imidazole and the semithiocarbazone moiety. Most potency gains came from
      substitution around the 6- and 7-positions of the quinoline ring. Replacement of
      the semithiocarbazone with a semicarbazone decreased potency but led to some
      measurable exposure.

PMID- 21074994
TI  - Novel 2,3,4,5-tetrahydro-benzo[d]azepine derivatives of 2,4-diaminopyrimidine,
      selective and orally bioavailable ALK inhibitors with antitumor efficacy in ALCL
      mouse models.
AB  - The synthesis and biological evaluation of potent and selective anaplastic
      lymphoma kinase (ALK) inhibitors from a novel class of 2,4-diaminopyrimidines,
      incorporating 2,3,4,5-tetrahydro-benzo[d]azepine fragments, is described. An
      orally bioavailable analogue (18) that displayed antitumor efficacy in ALCL
      xenograft models in mice was identified and extensively profiled.

PMID- 21074995
TI  - Reactions of nitroxides. Part X: antifungal activity of selected sulfur and
      selenium derivatives of 2,2,6,6-tetramethylpiperidine.
AB  - The antifungal activity of nitroxyl radicals-derivatives of 2,2,6,6
      tetramethylpiperidine-1-oxyl with reactive substituents 4-isothiocyanato-, 4
      isocyano-, and 4-isoselenocyanato- and of N-formyl-, N-thioformyl-, N
      selenoformyl-derivatives of 2,2,6,6-tetramethylpiperidine was investigated. Those
      of the above compounds, which contain a sulfur or selenium atom are the most
      active against four fungus plant patogens: Botrytiscinerea, Fusariumculmorum,
      Phytophthoracactorum, Rhizoctoniasolani. 4-Isoselenocyanato-2,2,6,6
      tetramethylpiperidine-1-oxyl proved to be the most active compound.

PMID- 21074996
TI  - Charcot-Marie-Tooth 1A patients with low level of impairment have a higher energy
      cost of walking than healthy individuals.
AB  - The study aimed at quantifying the walking energy cost of a group of Charcot
      Marie-Tooth 1A patients (CMT1A), with low severity of walking impairment, in
      comparison with healthy individuals. Oxygen uptake was measured in 8 patients
      (age-range 20-48 years; Barthel >90; Tinetti >20) and 8 healthy individuals,
      matched for age and gender, when walking on a circuit for 5-min at their self
      selected speeds ("slow", "comfortable" and "fast"). Both comfortable and fast
      speeds were lower in patients than in the control group (0.92+/-0.16 vs 1.16+/
      0.22 and 1.27+/-0.27 vs 1.61+/-0.22 m s-1, respectively; P<0.05), whereas walking
      energy cost per unit of distance was higher in patients than in the control group
      (P<0.05) at both "comfortable" (2.27+/-0.35 vs 1.92+/-0.21 J kg-1m-1) and "fast"
      speed (3.05+/-0.35 vs 2.37+/-0.42 J kg-1m-1). CMT1A patients, therefore, choose
      to walk slower but with higher metabolic cost compared to healthy individuals,
      despite no clinically evident walking impairment, which is likely due to altered
      walking patterns.

PMID- 21074997
TI  - Translational and rotational knee joint stability in anterior and posterior
      cruciate-retaining knee arthroplasty.
AB  - This study investigated passive translational and rotational stability properties
      of the intact knee joint, after bicruciate-retaining bi-compartmental knee
      arthroplasty (BKA) and after posterior cruciate retaining total knee arthroplasty
      (TKA). Fourteen human cadaveric knee specimens were used in this study, and a
      robotic manipulator with six-axis force/torque sensor was used to test the joint
      laxity in anterior-posterior translation, valgus-varus, and internal-external
      rotation. The results show the knee joint stability after bicruciate-retaining
      BKA is similar to that of the native knee. On the other hand, the PCL-retaining
      TKA results in inferior joint stability in valgus, varus, external rotation,
      anterior and, surprisingly, posterior directions. Our findings suggest that,
      provided functional ligamentous structures, bicruciate-retaining BKA is a
      biomechanically attractive treatment for joint degenerative disease.

PMID- 21074998
TI  - Synthesis, binding studies and molecular modeling of novel cannabinoid receptor
      ligands.
AB  - In the present work, we report upon the design, synthesis and biological
      evaluation of new anandamide derivatives obtained by modifications of the fatty
      acyl chain and/or of the ethanolamide 'tail'. The compounds are of the general
      formula: 6-(substituted-phenyl)/naphthyl-4-oxohex-5-enoic acid N-substituted
      amide and 7-naphthyl-5-oxohept-6-enoicacid N-substituted amide. The novel
      compounds had been evaluated for their binding affinity to CB1/CB2 cannabinoid
      receptors, binding studies showed that some of the newly developed compounds have
      measurable affinity and selectivity for the CB2 receptor. Compounds XI and XVIII
      showed the highest binding affinity for CB2 receptor. None of the compounds
      exhibited inhibitory activity towards anandamide hydrolysis, thus arguing in
      favor of their enzymatic stability. The structure-activity relationship has been
      extensively studied through a tailor-made homological model using constrained
      docking in addition to pharmacophore analysis, both feature and field based.

PMID- 21074999
TI  - Carbon-14 analysis in solidified product of non-metallic solid waste by a
      combination of alkaline fusion and gaseous CO2 trapping.
AB  - In order to establish a simple and rapid analytical method for (14)C in
      solidified products made from non-metallic low-level radioactive solid wastes
      such as concrete, mortar and glass by melting treatment, a radiochemical analysis
      in combination with alkaline fusion as a sample decomposition method was
      examined. A simulated solidified product containing (14)C, which was prepared by
      using nuclear reaction (14)N(n, p)(14)C with thermal neutron irradiation, was
      analyzed by the present method to compare with a conventional radiochemical
      analysis using oxidizing combustion. The reproducible and quantitative recovery
      of (14)C from the simulated solidified product indicates that the present method
      is more efficient for (14)C analysis in solidified products than the conventional
      method using oxidizing combustion.

PMID- 21075000
TI  - Light output of EJ228 scintillation neutron detectors.
AB  - The light output of neutron detectors based on the plastic scintillator EJ228 is
      studied as a function of neutron energy using a time tagged (252)Cf source.
      Calibration of the light output scale is performed by fitting the experimental
      distribution of Compton scattering events of photons from a (22)Na source with a
      response function obtained by Gaussian smearing of the predicted line-shape. The
      light output curve as well as the pulse height resolution for the EJ228
      scintillators is very close (within 5%) to those recently reported for NE213 type
      organic liquid scintillators.

PMID- 21075001
TI  - Flowability analysis of uranium dioxide powder at different temperatures
      containing different lubricants.
AB  - Powder flowability characteristics are often intentionally modified in order to
      improve their production process. The UO(2) pellet manufacturing process can
      consist of many steps, e.g. milling, granulation, homogenization, die filling for
      pressing, etc. By the addition of flow additives, lubricants or glidants the
      desired workability can be achieved. Temperature also influences the powder
      processability, leading to an easier or more complex powder flow. The work aims
      to determine some flowability characteristics for UO(2) powder at different
      temperatures.

PMID- 21075002
TI  - In silico analysis reveals that several tomato microRNA/microRNA* sequences
      exhibit propensity to bind to tomato leaf curl virus (ToLCV) associated genomes
      and most of their encoded open reading frames (ORFs).
AB  - Tomato leaf curl virus (ToLCV) is a member of family geminiviridae that
      constitute rapidly emerging group of phytopathogens posing threat to a large
      number of vegetable crops worldwide. Three different genomes are found to be
      associated with ToLCV viz., DNA-A, DNA-B and beta satellite DNA. MicroRNAs (miRs)
      are known to govern several fundamental processes in eukaryotes, including basal
      defense mechanisms. In animals, it has been demonstrated that certain host miRs
      prevent viral establishment by directly interfering with pathogen replication or
      by binding to viral transcripts. However, in spite of the existence of huge
      families of phytopathogenic viruses, no such mechanism has been observed in
      plants. In the present study, we performed in silico analysis to investigate
      whether tomato encoded miR/miR* sequences possess any potential to bind to viral
      genome and/or encoded ORFs. We observed that different sequences can bind to
      ToLCNDV DNA-A, ToLCNDV DNA-B and ToLCNDV associated DNA beta genomes and most of
      the encoded ORFs. Interestingly, our analysis revealed that several miR* species
      could similarly target genome and ORFs of ToLCNDV suggesting novel role of miR*
      in host defense response. This observation holds much importance as miR*
      molecules are presently thought to follow degradation pathway and are not
      assigned with any function. Moreover, we could predict targets for these miR*
      sequences that are generally involved in plant metabolism. Overall, these results
      shed light on new paradigm of intricate host-pathogen interactions via miRNA
      pathway.

PMID- 21075003
TI  - An innovative technique to control bleeding with vacuum device.
AB  - Bleeding is one of the major problems during surgery as well as in cases of
      accidental vascular injury. Control of bleeding can be life threatening in two
      surgical circumstances: when the wound is difficult to expose, and when the
      tissue too fragile to suture. Following more than 100 animal tests, we developed
      an innovative vacuum-based suction device, which enables us to address this
      challenge. We set up a proof-of-concept protocol in humans and report here our
      first clinical experience.

PMID- 21075004
TI  - Peritoneal cytokines as early markers of peritonitis following surgery for
      colorectal carcinoma: a prospective study.
AB  - This study was to investigate if measurement of peritoneal cytokines is valuable
      for an early diagnosis of peritonitis following colorectal surgery. One hundred
      consecutive patients who were to undergo elective resection for carcinoma of the
      sigmoid colon or the rectum were investigated. Abdominal exudate was obtained
      from a drainage tube daily after surgery for measuring interleukin (IL)-1beta, IL
      6 and tumour necrosis factor (TNF)-alpha. The relationship between peritoneal
      cytokine levels during the first 3 days after surgery and the development of
      peritonitis was investigated. Eight patients developed postoperative peritonitis
      due to anastomotic leakage and pelvic abscess, which was diagnosed on
      postoperative days 5-8. Peritoneal cytokine levels on postoperative days 1 and 2
      were not significantly different between the 8 patients who developed peritonitis
      and 92 patients who did not: day 1, IL-1betaP=0.32, IL-6 P=0.45, TNF-alphaP=0.85;
      day 2, IL-1betaP=0.26, IL-6 P=0.68, TNF-alphaP=0.22. In contrast, the cytokine
      levels on day 3 were significantly higher in patients who developed peritonitis
      as compared with patients who did not: IL-1betaP=0.008, IL-6 P<0.0001, TNF
      alphaP=0.0001. The cytokines significantly increased during the first 3 days in
      patients who developed peritonitis: IL-1betaP=0.049, IL-6 P=0.03, TNF
      alphaP=0.01, while significantly decreased in patients who did not: IL
      1betaP<0.0001, IL-6 P<0.0001, TNF-alphaP<0.0001. The outcomes of this
      investigation showed that the rise in peritoneal IL-1beta, IL-6 and TNF-alpha
      levels may be an additional early diagnostic predictor of intraabdominal
      complications following colorectal surgery.

PMID- 21075005
TI  - Apoptotic neutrophils and nitric oxide regulate cytokine production by IFN-gamma
      stimulated macrophages.
AB  - Early apoptotic neutrophils but not secondary necrotic ones down-regulate LPS
      induced proinflammatory cytokine production of macrophages, thereby contributing
      to the resolution of inflammation. IFN-gamma is also a well-known stimulant of
      macrophages, but how the apoptotic neutrophils affect IFN-gamma-stimulated
      macrophages remains largely unexplored. Since IFN-gamma induces the expression of
      inducible nitric oxide (NO) synthase, we examined the production of NO and
      various cytokines, including MIP-2, TNF-alpha, IL-12p40, IL-6, IL-10, and TGF
      beta, by IFN-gamma-stimulated murine macrophages, the effect of coculturing the
      macrophages with early apoptotic or secondary necrotic neutrophils, and the
      regulatory role of NO in such cocultures. IFN-gamma induced significant
      production of NO, IL-12p40, and IL-6 by macrophages, but not other cytokines.
      Early apoptotic neutrophils but not secondary necrotic ones promoted NO
      production, whereas secondary necrotic ones and their supernatants promoted TNF
      alpha production. In contrast, both early apoptotic and secondary necrotic
      neutrophils suppressed IL-12p40 and IL-6 production. Furthermore, macrophages
      from inducible NO synthase-deficient mice produced significantly higher levels of
      MIP-2 than those from wild-type mice. Consistent with this, treatment of
      macrophages with l-NAME, an NO synthase inhibitor, also induced the production of
      a large amount of MIP-2. In conclusion, this study suggests that early apoptotic
      neutrophils are critical in the resolution of inflammation, but that secondary
      necrotic neutrophils may not cause an inflammatory response. Apoptotic
      neutrophils, however, appear not to modulate cytokine production via NO.

PMID- 21075006
TI  - Piper rhythm of the electromyograms of the abductor pollicis brevis muscle during
      isometric contractions.
AB  - A temporal pattern coding, synchronization and rhythmicity form an integral part
      of central nervous system information controlling the muscle activation. Rhythmic
      oscillations of muscles at frequencies of 35-60 Hz were already noted in the
      electromyograms by Piper (1907). The purpose of this study was to resolve the
      Piper rhythm in the EMG of the APB muscle and report the pacing frequencies of
      the Piper rhythm. The Piper rhythm was identified using the power of the EMG
      signals extracted by a wavelet transform at higher frequencies (170-271 Hz). The
      results showed distinct power of the intensity extracted by the wavelets in a
      frequency band ranging from about 30-60 Hz. The band was reflected in the power
      spectra of the EMG intensity and in the first eigenvector of a principal
      component analysis of the power spectra. The fact that the Piper rhythm shown in
      this study for the APB muscle yielded a large contribution to the total power
      means that one can use the frequency and amplitude of the Piper rhythm in future
      analysis of EMG signals to monitor the influence and changes of the central
      command.

PMID- 21075007
TI  - Noninflammatory cerebral vasculopathy associated with recurrent ischemic strokes.
AB  - Recurrent ischemic strokes often have uncommon causes in young adults. Vascular
      abnormalities may be considered as a possible etiology. We report a 36-year-old
      man who experienced recurrent cryptogenic ischemic strokes despite medical
      therapy. Conventional cerebral angiography was unrevealing. Subsequent brain
      biopsy revealed a distinctive histopathological pattern of abnormal perivascular
      collagen deposition without inflammation. Recurrent cryptogenic strokes may have
      novel etiologies, and brain biopsy should be considered when standard diagnostic
      tests fail.

PMID- 21075008
TI  - Is there a "special relationship" between unconscious emotions and visual
      imagery? Evidence from a mental rotation test.
AB  - There is an increasing interest in the relationship between imagery and emotion
      (e.g., Holmes & Mathews, 2005). The present research examined whether unconscious
      emotions affect visual imagery. In particular, participants were invited to
      perform a mental rotation test following subliminal presentation of happy, sad
      and neutral expressions. This study revealed an increase in mental rotation
      abilities after unconscious visual processing of emotional expressions.
      Altogether, these findings support the hypothesis of a bidirectional relationship
      between imagery and emotions.

PMID- 21075009
TI  - Faces and ascriptions: mapping measures of the self.
AB  - The 'self' is increasingly used as a variable in cognitive experiments and
      correlated with activity in particular areas in the brain. At first glance, this
      seems to transform the self from an ephemeral theoretical entity to something
      concrete and measurable. However, the transformation is by no means
      unproblematic. We trace the development of two important experimental paradigms
      in the study of the self, self-face recognition and the adjective self ascription
      task. We show how the experimental instrumentalization has gone hand in hand with
      a simplification of the self-concept, and how more conceptual and theoretical
      reflections on the structure, function and nature of self have either disappeared
      altogether or receded into the background. We argue that this development impedes
      and complicates the interdisciplinary study of self.

PMID- 21075010
TI  - Cognitive and emotional processes during dreaming: a neuroimaging view.
AB  - Dream is a state of consciousness characterized by internally-generated sensory,
      cognitive and emotional experiences occurring during sleep. Dream reports tend to
      be particularly abundant, with complex, emotional, and perceptually vivid
      experiences after awakenings from rapid eye movement (REM) sleep. This is why our
      current knowledge of the cerebral correlates of dreaming, mainly derives from
      studies of REM sleep. Neuroimaging results show that REM sleep is characterized
      by a specific pattern of regional brain activity. We demonstrate that this
      heterogeneous distribution of brain activity during sleep explains many typical
      features in dreams. Reciprocally, specific dream characteristics suggest the
      activation of selective brain regions during sleep. Such an integration of
      neuroimaging data of human sleep, mental imagery, and the content of dreams is
      critical for current models of dreaming; it also provides neurobiological support
      for an implication of sleep and dreaming in some important functions such as
      emotional regulation.

PMID- 21075011
TI  - Antiepileptic drug therapy the story so far.
AB  - The story began on 11th May 1857 when Charles Locock commented in the Lancet on
      his use of potassium bromide in 15 cases of "hysterical" epilepsy in young women.
      The next development was the serendipitous discovery of the anticonvulsant
      properties of phenobarbital by Alfred Hauptmann in 1912. This predated by more
      than 20 years the screening of potential therapeutic agents against "electrical
      seizures" in cats by Houston Merritt and Tracy Putnam. The result was the
      launching of phenytoin in 1938. Next came primidone, ethosuximide, carbamazepine
      and valproic acid, all of which can be regarded as first generation antiepileptic
      drugs (AEDs). Shortly after their synthesis, the benzodiazepines were rapidly
      recognised as having anticonvulsant activity. The modern era focused on the
      systematic screening of many thousands of compounds against rodent seizure models
      under the Anticonvulsant Drug Development Program in the US. This resulted in the
      global licensing, in chronological order, of vigabatrin, zonisamide,
      oxcarbazepine, lamotrigine, felbamate, gabapentin, topiramate, tiagabine,
      levetiracetam, pregabalin and lacosamide. Rufinamide is available in the US and
      Europe for Lennox-Gastaut syndrome and stiripentol has been made available for
      Dravet syndrome under the European orphan drug scheme. Eslicarbazepine can be
      prescribed in Europe for partial seizures, but not in the US. Has all this
      activity improved the lives of people with epilepsy? The short answer is-probably
      yes, but not by very much! This paper will conclude with a precis of the views of
      a selected group of paediatric and adult epileptologists on the advances in
      pharmacological management achieved over the last 20 years.

PMID- 21075012
TI  - What Epilepsy Action means for me.

PMID- 21075013
TI  - Epilepsy stigma: moving from a global problem to global solutions.
AB  - Stigma and exclusion are common features of epilepsy in both the developed and
      developing countries and a major contributor to the burden associated with the
      condition. Reducing the stigma of epilepsy is key to reducing its impact and so
      improving quality of life. The social consequences of having epilepsy can be
      enormous, be it that they vary from country to country, based on cultural
      differences and economic circumstances. The most significant problems people with
      epilepsy encounter in daily life often are not related to the severity of the
      condition, but stem from concepts of epilepsy held by the general public. In this
      paper, I review the history of epilepsy and consider how different historical and
      cultural understandings of epilepsy have determined the experience of stigma for
      those affected by it. I consider how this history of stigma impacts on the
      position of people with epilepsy today, many of whom may still experience serious
      limitations to their enjoyment of economic, social and cultural rights and have
      many unmet needs in the areas of civil rights, education, employment, residential
      and community services, and access to appropriate health care. Finally, I will
      discuss some current initiatives aimed at addressed the issue of epilepsy stigma
      worldwide, which offer hope of an end to the social exclusion and prejudice which
      people with epilepsy have endured for so long.

PMID- 21075014
TI  - Primary motor cortex alterations in a compound heterozygous form of Unverricht
      Lundborg disease (EPM1).
AB  - PURPOSE: Unverricht-Lundborg disease (EPM1) is the most common form of
      progressive myoclonus epilepsies. The genetic background is a homozygous
      dodecamer repeat extension mutation in the cystatin B (CSTB) gene. However,
      mutations occurring in a compound heterozygous form with the expansion mutation
      have also been reported. In Finland, we have found five EPM1 patients compound
      heterozygous for the dodecamer repeat expansion and the c.202C>T mutation in the
      CSTB gene (chEPM1). There are no previous clinical or neurophysiological studies
      on these patients. Thus, we aimed to characterize possible functional alterations
      in primary motor cortical areas. METHODS: Five chEPM1 patients were compared with
      homozygous patients and healthy controls. All patients underwent a clinical
      evaluation to characterize the severity of the symptoms. Navigated transcranial
      magnetic stimulation (TMS) was used to study cortical excitability by determining
      the motor thresholds (MT), silent periods (SP) and motor evoked potential (MEP)
      characteristics. Continuous electroencephalography (EEG) was recorded during the
      measurements. Voxel-based MRI morphometry (VBM) was used to study differences in
      gray matter volume. RESULTS: The chEPM1 patients exhibited an inhibitory cortical
      tonus reflected as elevated MTs and prolonged SPs. EEG showed spontaneous focal
      epileptiform activity in centro-temporal and parietal areas in addition to more
      widespread and generalized discharges. VBM revealed loss of gray matter volume in
      primary motor cortical areas and thalami. DISCUSSION: The chEPM1 patients
      exhibited functional and structural changes in primary motor cortical areas. The
      functional changes are more profound as compared to homozygous patients,
      suggesting a neurophysiological background for the more severe clinical symptoms.

PMID- 21075015
TI  - Gallbladder cancer: differences in presentation, surgical treatment, and survival
      in patients treated at centers in three countries.
AB  - BACKGROUND: Gallbladder cancer (GBCA) is a rare malignancy with a variable
      incidence worldwide. This study analyzed GBCA patients treated at centers in 3
      countries. The aim was to assess for location-specific differences in
      presentation and outcomes, which might suggest differences in pathogenesis or
      disease biology. STUDY DESIGN: Data for consecutive patients submitted to
      operation at Instituto Oncologico Fundacion Arturo Lopez Perez (FALP, Chile),
      Yokohama City University (YCU, Japan), and Memorial Sloan-Kettering Cancer Center
      (MSKCC, USA) between 1999 and 2007 were studied retrospectively. Patient
      demographics, disease- and treatment-related variables and outcomes were analyzed
      by chi-square, Kruskal-Wallis, and log-rank test. RESULTS: Two hundred sixty-one
      patients (MSKCC, 130; FALP, 85; YCU, 46) underwent exploration, and 160 (MSKCC,
      91; FALP, 33; YCU, 36) underwent R0 resection. Patients treated at FALP were
      younger (median 57 years, p < 0.001) and more often female (80%, p < 0.005); at
      YCU there were fewer patients with incidental tumors (19.5% compared with more
      than 60% at FALP and MSKCC, p < 0.001). En bloc liver and bile duct resections
      were performed more commonly at MSKCC and YCU (p < 0.001). Patients treated at
      FALP had more advanced tumor stage compared with those treated at MSKCC and YCU
      (p < 0.001). Disease-specific survival (DSS) was not different among the groups
      when patients submitted to an R0 resection were analyzed (p = 0.12). On
      multivariate analysis, T-stage, nodal involvement, and bile duct involvement were
      predictors of DSS; center was not significant. CONCLUSIONS: Despite some
      differences in presentation, disease extent, and surgical treatment, DSS after
      curative intent resection was similar among all 3 groups. The most important
      predictors of outcomes were related to tumor extent rather than country of
      origin.

PMID- 21075016
TI  - Patient size compensated automatic tube current modulation in multi-detector row
      CT of the abdomen and pelvis.
AB  - RATIONALE AND PURPOSE: To evaluate the performance of a patient size-compensated
      automatic tube current modulation (PSC-AutomA) technique from the perspectives of
      image quality and radiation dose in multi-detector-row computed tomography (MDCT)
      scan of the abdomen and pelvis. MATERIALS AND METHODS: Institutional review board
      approval was obtained and the study was Health Insurance Portability and
      Accountability Act-compliant. One hundred and seventeen patients (mean age: 48.8
      years; range: 17-89 years; male/female: 57/60) underwent abdominal-pelvic CT scan
      on a 64-slice MDCT using the noise indexes (NI) recommended by the PSC-AutomA
      technique. Two radiologists independently evaluated all examinations for noise,
      streak artifacts, and diagnostic acceptability at the dome of liver, porta
      hepatis, and the upper margin of acetabulum. The CT dose index (CTDI) volume and
      effective dose of the CT performed using a recommended NI were compared to the CT
      performed using a fixed NI of 12. Statistical analysis of the data was performed
      with nonparametric tests. RESULTS: The NI recommended by the PSC-AutomA technique
      was strongly correlated with patient size (r = 0.98, P < .001) with a mean NI of
      14.2 HU. The recommended NI of 98.2% (115/117) patients was different from the
      fixed NI of 12. Approximately 71.8% (84/117) subjects were scanned with a NI
      higher than 12, whereas 26.5% (31/117) subjects were scanned with a NI lower than
      12. All examinations (100%; 117/117) were graded as possessing diagnostic image
      quality. Compared with the CT performed by using a fixed NI 12, the overall CTDI
      and effective dose reduction by the PSC-AutomA technique were 11.1% and 11.8%,
      respectively. CONCLUSION: The PSC-AutomA technique can recommend an appropriate
      NI in MDCT scan of the abdomen and pelvis according to patient size, allowing a
      balanced optimization of both radiation dose and image quality, simultaneously.

PMID- 21075017
TI  - Steerable catheter microcoils for interventional MRI reducing resistive heating.
AB  - RATIONALE AND OBJECTIVES: The aims of this study were to assess resistive heating
      of microwires used for remote catheter steering in interventional magnetic
      resonance imaging and to investigate the use of alumina to facilitate heat
      transfer to saline flowing in the catheter lumen. MATERIALS AND METHODS: A
      microcoil was fabricated using a laser lathe onto polyimide-tipped or alumina
      tipped endovascular catheters. In vitro testing was performed on a 1.5-T magnetic
      resonance system using a vessel phantom, body radiofrequency coil, and steady
      state pulse sequence. Resistive heating was measured with water flowing over a
      polyimide-tip catheter or saline flowing through the lumen of an alumina-tip
      catheter. Preliminary in vivo testing in porcine common carotid arteries was
      conducted with normal blood flow or after arterial ligation when current was
      applied to an alumina-tip catheter for up to 5 minutes. RESULTS: After
      application of up to 1 W of direct current power, clinically significant
      temperature increases were noted with the polyimide-tip catheter: 23 degrees C/W
      at zero flow, 13 degrees C/W at 0.28 cm(3)/s, and 7.9 degrees C/W at 1 cm(3)/s.
      Using the alumina-tip catheter, the effluent temperature rise using the lowest
      flow rate (0.12 cm(3)/s) was 2.3 degrees C/W. In vivo testing demonstrated no
      thermal injury to vessel walls at normal and zero arterial flow. CONCLUSIONS:
      Resistive heating in current carrying wire pairs can be dissipated by saline
      coolant flowing within the lumen of a catheter tip composed of material that
      facilitates heat transfer.

PMID- 21075018
TI  - An ultrasound model to discriminate the risk of thyroid carcinoma.
AB  - RATIONALE AND OBJECTIVES: Thyroid nodules are common on ultrasonographic
      examination and are mostly benign. Ultrasound characteristics may help
      discriminate thyroid carcinoma (TC) from benign nodules. The aims of this study
      were to identify ultrasonographic characteristics associated with TC and to
      validate a previously proposed model based on the presence of three
      ultrasonographic characteristics. MATERIALS AND METHODS: From a protocolized
      prospective registry of 1108 fine needle aspiration biopsies performed during a
      16-month period at an ambulatory center, the ultrasonographic characteristics of
      TC and non-TC biopsies were compared. Adjusted odds ratios (ORs) and likelihood
      ratios for TC were estimated for eight combinations of three previously
      identified characteristics (microcalcifications, hypoechogenicity, and irregular
      borders). RESULTS: Microcalcifications (OR, 6.6; 95% confidence interval [CI],
      4.4-9.9), hypoechogenicity (OR, 4.7; 95% CI, 2.8-8.0), and irregular borders (OR,
      4.3; 95% CI, 2.8-6.5) were independently associated with TC. When added to a
      logistic regression model, the three ultrasonographic characteristics remained
      statistically significant. In the absence of these three features, the likelihood
      ratio for TC was 0.1 (95% CI, 0.0-0.2), while in their simultaneous presence, the
      likelihood ratio was 11 (95% CI, 6.6-19.0). CONCLUSIONS: The absence or
      simultaneous presence of three simple ultrasonographic characteristics generates
      a large change of pretest probability of TC and could avoid unnecessary fine
      needle aspiration biopsy.

PMID- 21075019
TI  - RF Heating of MRI-Assisted Catheter Steering Coils for Interventional MRI.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was too assess magnetic resonance
      imaging (MRI) radiofrequency (RF)-related heating of conductive wire coils used
      in magnetically steerable endovascular catheters. MATERIALS AND METHODS: A three
      axis microcoil was fabricated onto a 1.8Fr catheter tip. In vitro testing was
      performed on a 1.5-T MRI system using an agarose gel-filled vessel phantom, a
      transmit-receive body RF coil, a steady-state free precession pulse sequence, and
      a fluoroptic thermometry system. Temperature was measured without simulated blood
      flow at varying distances from the magnet isocenter and at varying flip angles.
      Additional experiments were performed with laser-lithographed single-axis
      microcoil-tipped microcatheters in air and in a saline bath with varied grounding
      of the microcoil wires. Preliminary in vivo evaluation of RF heating was
      performed in pigs at 1.5 T with coil-tipped catheters in various positions in the
      common carotid arteries with steady-state free precession pulse sequence on and
      off and under physiologic-flow and zero-flow conditions. RESULTS: In tissue
      mimicking agarose gel, RF heating resulted in a maximal temperature increase of
      0.35 degrees C after 15 minutes of imaging, 15 cm from the magnet isocenter. For
      a single-axis microcoil, maximal temperature increases were 0.73 degrees C to
      1.91 degrees C in air and 0.45 degrees C to 0.55 degrees C in saline. In vivo,
      delayed contrast-enhanced MRI revealed no evidence of vascular injury, and
      histopathologic sections from the common carotid arteries confirmed the lack of
      vascular damage. CONCLUSIONS: Microcatheter tip microcoils for endovascular
      catheter steering in MRI experience minimal RF heating under the conditions
      tested. These data provide the basis for further in vivo testing of this
      promising technology for endovascular interventional MRI.

PMID- 21075020
TI  - Ultrasound biomicroscopy for the detection of early osteoarthritis in an animal
      model.
AB  - RATIONALE AND OBJECTIVES: Osteoarthritis (OA) is a common disease, and early
      diagnosis is essential for preventing further cartilage destruction and
      decreasing severe complications. Ultrasound biomicroscopy (UBM) is sensitive for
      detecting minute lesions in tissue because of its higher resolution, but its B
      mode characterization of the early stage of OA has not been widely studied. The
      aim of this study was to determine the usefulness of UBM for detecting the early
      stage of OA using a rabbit model of early OA. MATERIALS AND METHODS: Eighteen
      adult New Zealand White female rabbits were used in this study, which included 12
      rabbits that underwent transections of the left anterior cruciate ligament and
      six control rabbits. At 2, 4, and 6 weeks after surgery, four experimental
      rabbits and two control rabbits were euthanized. UBM was performed to evaluate
      the articular cartilage surfaces of the left knee, using a 55-MHz transducer. All
      the articular cartilage surfaces were independently assessed in blinded fashion
      by two radiologists for the severity of OA. The value of UBM, interobserver
      reliability, and the concordance between UBM and pathologic grades were
      determined. RESULTS: For the first radiologist, the sensitivity, specificity,
      positive predictive value, and negative predictive value of UBM for the diagnosis
      of OA were 91%, 83%, 89%, and 86%, respectively. For the second radiologist, the
      sensitivity, specificity, positive predictive value, and negative predictive
      value of UBM were 93%, 86%, 91%, and 89%, respectively. The concordance between
      UBM and pathologic grades for both radiologists was high (kappa = 0.72 and 0.76),
      and the interobserver agreement was high (kappa = 0.80). CONCLUSIONS: UBM can be
      used to evaluate cartilage defects in an animal model, and further study is
      needed to determine whether this technique can be valuable for detecting early OA
      in humans.

PMID- 21075021
TI  - Medical students' preferences in radiology education a comparison between the
      Socratic and didactic methods utilizing powerpoint features in radiology
      education.
AB  - RATIONALE AND OBJECTIVES: The Socratic method has long been a traditional
      teaching method in medicine and law. It is currently accepted as the standard of
      teaching in clinical wards, while the didactic teaching method is widely used
      during the first 2 years of medical school. There are arguments in support of
      both styles of teaching. MATERIALS AND METHODS: After attending a radiology
      conference demonstrating different teaching methods, third-year and fourth-year
      medical students were invited to participate in an online anonymous survey.
      RESULTS: Of the 74 students who responded, 72% preferred to learn radiology in an
      active context. They preferred being given adequate time to find abnormalities on
      images, with feedback afterward from instructors, and they thought the best
      approach was a volunteer-based system of answering questions using the Socratic
      method in the small group. They desired to be asked questions in a way that was
      constructive and not belittling, to realize their knowledge deficits and to have
      daily pressure to come prepared. The respondents thought that pimping was an
      effective teaching tool, supporting previous studies. CONCLUSIONS: When teaching
      radiology, instructors should use the Socratic method to a greater extent.
      Combining Socratic teaching with gentle questioning by an instructor through the
      use of PowerPoint is a preferred method among medical students. This information
      is useful to improve medical education in the future, especially in radiology
      education.

PMID- 21075022
TI  - Gaucher disease type I: assessment of basal metabolic rate in patients from
      southern Brazil.
AB  - INTRODUCTION: Gaucher disease (GD) is characterized by clinical heterogeneity and
      is associated with metabolic abnormalities such as increased resting energy
      expenditure. OBJECTIVES: To assess the basal metabolic rate (BMR) of patients
      with GD type I followed at the Gaucher Disease Reference Center of Rio Grande do
      Sul, Brazil. PATIENTS AND METHODS: Fourteen patients (male=6) and 14 healthy
      controls matched by gender, age and body mass index (BMI) were included in the
      study. The nutritional status of patients was assessed by BMI. The BMR was
      measured by indirect calorimetry. In two patients, it was possible to perform BMR
      in the pre- and the post-treatment periods. RESULTS: Mean age and BMI of patients
      and controls were, respectively, 32.8 +/- 17.6 and 32.1 +/- 16.6 years and 23.3
      +/- 3.1 and 22.4 +/- 3.1 kg/m(2). Twelve patients were receiving enzyme
      replacement therapy (ERT) with imiglucerase (mean duration of treatment=5.2 +/-
      4.3 years; mean dosage of imiglucerase=24.2 +/- 7.3 UI/kg/inf). Five patients
      (36%) were overweight, and nine (64%) were normal weight. Mean BMR of patients on
      ERT was 27.1% higher than that of controls (p=0.007). There was no difference
      between the BMR of patients on ERT and not on ERT (n=4) (p=0.92). Comparing the
      BMR of patients on ERT and their controls with the BMR estimated by the Harris
      Benedict equation, the BMR of patients was 6.3% higher than the estimated (p =
      0.1), while the BMR of their controls was 17.0% lower than the estimated (p =
      0.001). CONCLUSION: Most treated GD type I patients were normal weight. The
      patients including those on ERT showed higher BMR when compared to controls.
      Imiglucerase is probably unable to normalize the hypermetabolism presented by GD
      type I patients. Additional studies should be performed to confirm our findings.

PMID- 21075023
TI  - Elevated CSF-lactate is a reliable marker of mitochondrial disorders in children
      even after brief seizures.
AB  - BACKGROUND: Increased lactate is an important biochemical marker in diagnosis of
      children with suspicion of mitochondrial disorders. A diagnostic dilemma may
      originate if analyses are performed after seizures, when the increased lactate
      levels may be considered to result from the seizures. To address this problem, we
      ascertained the diagnostic value of lactate and alanine in blood (B) and
      cerebrospinal fluid (CSF) in children with mitochondrial disorders (n = 24),
      epilepsy (n = 32), psychomotor retardation (n = 23), meningitis (n = 12) and
      meningism (n = 16). METHODS: Lactate concentration was measured using a
      spectrophotometric method. Amino acids in serum and CSF were analyzed by ion
      exchange chromatography with ninhydrin detection. RESULTS: Average blood and CSF
      lactate levels were significantly higher in children with mitochondrial disorders
      (3.87 +/- 0.48 and 4.43 +/- 0.55 mmol/l) and meningitis (2.77 +/- 0.45 and 8.58
      +/- 1.08 mmol/l) than in children with epilepsy (1.72 +/- 0.13 and 1.62 +/- 0.04
      mmol/l), psychomotor retardation (1.79 +/- 1.40 and 1.68 +/- 0.06 mmol/l) or
      meningism (1.70 +/- 0.13 and 1.64 +/- 0.07 mmol/l). Blood and CSF-alanine levels
      were also higher in children with mitochondrial disorders (558 +/- 44 and 51 +/-
      8 MUmol/l) than in children with epilepsy (327 +/- 23 and 27 +/- 3 MUmol/l) or
      psychomotor retardation (323 +/- 27 and 26 +/- 3 MUmol/l). The CSF-lactate levels
      of children with epilepsy were similar whether the samples were obtained 3 +/-
      0.6 h after an attack of brief seizures or from children without history of
      recent seizures. CONCLUSION: Elevated cerebrospinal fluid lactate level is a
      reliable marker pointing to mitochondrial origin of disease, even in children who
      have recently suffered short-lasting seizures. Some children with mitochondrial
      disorders manifest only mild or intermittent elevation of lactate levels.

PMID- 21075024
TI  - Using discrete choice experiments to inform randomised controlled trials: an
      application to chronic low back pain management in primary care.
AB  - Pain Management Programmes (PMPs) are a multi-disciplinary approach to the
      management of chronic low back pain (CLBP). Notwithstanding evidence of
      effectiveness, successful take-up of programmes requires acceptability to
      patients. We used a discrete choice experiment to investigate patient preferences
      for alternative PMPs for managing CLBP in primary care. Specifically, we
      estimated the probability of uptake of alternative configurations of PMPs.
      Potential attributes and associated levels influencing take-up were identified
      through a systematic literature review, survey of current PMPs, expert
      consultation, and focus groups. Five attributes were included: content; provider;
      schedule; group size; and travel time to clinic. Four hundred and fourteen
      questionnaires were mailed to patients attending clinics and 124 questionnaires
      were returned suitable for analysis. Method of delivery influenced probability of
      take-up, with small group sizes and low intensity programmes over a prolonged
      period increasing the probabilities. Travel time was also important. However,
      providers and contents of PMPs were not main drivers of preferences, though those
      with more severe pain did prefer PMPs provided by more specialists. Probability
      of take-up increases when PMPs better reflect patient preferences. Given
      preferences, resource constraints, and evidence on clinical outcomes of
      alternative configurations it is suggested more resource-intensive PMPs be
      reserved for those with the most severe and disabling pain and less intensive
      programmes delivered over a longer time period in smaller groups for those with
      less severe pain. These findings can inform future randomised trials to evaluate
      acceptable PMPs in primary care.

PMID- 21075025
TI  - The passive transfer of immunoglobulin G serum antibodies from patients with
      longstanding Complex Regional Pain Syndrome.
AB  - BACKGROUND: The aetiology of Complex Regional Pain Syndrome (CRPS) is unknown.
      Recent evidence suggests that there may be autoantibodies directed against
      peripheral nerves, but it is unclear whether such autoantibodies are merely
      biomarkers or whether they cause or contribute to the underlying pathology. The
      transfer of disease after injection of a patient's serum or IgG fraction into
      mice ('passive transfer') is the classic way to demonstrate a functional role of
      autoantibodies. AIMS: Based on previous preliminary results, we wished to
      investigate whether the transfer of IgG antibodies affected mouse behaviour or
      produced signs of CRPS. METHODS: We injected purified serum-IgG from 12 patients
      and 12 controls into groups of 6-10 mice (~ 17 mg/mouse intraperitoneally) on 2
      consecutive days and looked for any evidence for altered behaviour or signs of
      CRPS. The observer, blinded as to test or control group, measured behaviour in
      the open field, stimulus-evoked pain and motor coordination, and inspected limbs
      for autonomic CRPS signs. RESULTS: Stimulus-evoked pain and autonomic signs were
      not detected, but CRPS-IgG induced significant depression of rearing behaviour
      (17.9 rears/3 min (n = 84) vs. 22.1 rears/3 min (n = 83), p = 0.0004), confirming
      previous observations in a single case study. Moreover, motor impairment, one of
      the four cardinal signs of CRPS, was evident in the three CRPS-IgG injected
      groups tested with a sensitive rota-rod protocol (p < 0.0001 vs. control-IgG
      injected groups). CONCLUSIONS: These results lend support to a pathophysiological
      role for IgG autoantibodies in CRPS.

PMID- 21075027
TI  - The parallel-antiparallel signal difference in double-wave-vector diffusion
      weighted MR at short mixing times: a phase evolution perspective.
AB  - Experiments with two diffusion weightings applied in direct succession in a
      single acquisition, so-called double- or two-wave-vector diffusion-weighting
      (DWV) experiments at short mixing times, have been shown to be a promising tool
      to estimate cell or compartment sizes, e.g. in living tissue. The basic theory
      for such experiments predicts that the signal decays for parallel and
      antiparallel wave vector orientations differ by a factor of three for small wave
      vectors. This seems to be surprising because in standard, single-wave-vector
      experiments the polarity of the diffusion weighting has no influence on the
      signal attenuation. Thus, the question how this difference can be understood more
      pictorially is often raised. In this rather educational manuscript, the phase
      evolution during a DWV experiment for simple geometries, e.g. diffusion between
      parallel, impermeable planes oriented perpendicular to the wave vectors, is
      considered step-by-step and demonstrates how the signal difference develops.
      Considering the populations of the phase distributions obtained, the factor of
      three between the signal decays which is predicted by the theory can be
      reproduced. Furthermore, the intermediate signal decay for orthogonal wave vector
      orientations can be derived when investigating diffusion in a box. Thus, the
      presented "phase gymnastics" approach may help to understand the signal
      modulation observed in DWV experiments at short mixing times.

PMID- 21075026
TI  - Combining steady-state and dynamic methods for determining absolute signs of
      hyperfine interactions: pulsed ENDOR Saturation and Recovery (PESTRE).
AB  - The underlying causes of asymmetric intensities in Davies pulsed ENDOR spectra
      that are associated with the signs of the hyperfine interaction are
      reinvestigated. The intensity variations in these asymmetric ENDOR patterns are
      best described as shifts in an apparent baseline intensity that occurs
      dynamically following on-resonance ENDOR transitions. We have developed an
      extremely straightforward multi-sequence protocol that is capable of giving the
      sign of the hyperfine interaction by probing a single ENDOR transition, without
      reference to its partner transition. This technique, Pulsed ENDOR Saturation and
      Recovery (PESTRE) monitors dynamic shifts in the 'baseline' following
      measurements at a single RF frequency (single ENDOR peak), rather than observing
      anomalous ENDOR intensity differences between the two branches of an ENDOR
      response. These baseline shifts, referred to as dynamic reference levels (DRLs),
      can be directly tied to the electron-spin manifold from which that ENDOR
      transition arises. The application of this protocol is demonstrated on (57)Fe
      ENDOR of a 2Fe-2S ferredoxin. We use the (14)N ENDOR transitions of the S =
      3/2[Fe(II)NO](2+) center of the non-heme iron enzyme, anthranilate dioxygenase
      (AntDO) to examine the details of the relaxation model using PESTRE.

PMID- 21075028
TI  - Simultaneous acquisition of pulse EPR orientation selective spectra.
AB  - High resolution pulse EPR methods are usually applied to resolve weak magnetic
      electron-nuclear or electron-electron interactions that are otherwise unresolved
      in the EPR spectrum. Complete information regarding different magnetic
      interactions, namely, principal components and orientation of principal axis
      system with respect to the molecular frame, can be derived from orientation
      selective pulsed EPR measurements that are performed at different magnetic field
      positions within the inhomogeneously broadened EPR spectrum. These experiments
      are usually carried out consecutively, namely a particular field position is
      chosen, data are accumulated until the signal to noise ratio is satisfactory, and
      then the next field position is chosen and data are accumulated. Here we present
      a new approach for data acquisition of pulsed EPR experiments referred to as
      parallel acquisition. It is applicable when the spectral width is much broader
      than the excitation bandwidth of the applied pulse sequence and it is
      particularly useful for orientation selective pulse EPR experiments. In this
      approach several pulse EPR measurements are performed within the waiting
      (repetition) time between consecutive pulse sequences during which spin lattice
      relaxation takes place. This is achieved by rapidly changing the main magnetic
      field, B(0), to different values within the EPR spectrum, performing the same
      experiment on the otherwise idle spins. This scheme represents an efficient
      utilization of the spectrometer and provides the same spectral information in a
      shorter time. This approach is demonstrated on W-band orientation selective
      electron-nuclear double resonance (ENDOR), electron spin echo envelope modulation
      (ESEEM), electron-electron double resonance (ELDOR)--detected NMR and double
      electron-electron resonance (DEER) measurements on frozen solutions of
      nitroxides. We show that a factors of 3-6 reduction in total acquisition time can
      be obtained, depending on the experiment applied.

PMID- 21075029
TI  - QM methods in structure based design: utility in probing protein-ligand
      interactions.
AB  - Small changes in ligand structure can lead to large unexpected changes in
      activity yet it is often not possible to rationalize these effects using
      empirical modeling techniques, suggesting more effective methods are required. In
      this study we investigate the use of high level QM methods to study the
      interactions found within protein-ligand complexes as improved understanding of
      these could help in the design of new, more active molecules. We study aspects of
      ligand binding in a set of protein ligand complexes containing ligand efficient,
      fragment-like inhibitors as these structures are often challenging to determine
      experimentally. To assess the reliability of our theoretical models we compare
      the MP2/6-31+G** QM results to the original X-ray coordinates and to QM/MM
      B3LYP/6-31G*//UFF results which we have previously reported. We also contrast
      these results with data obtained from an analysis of the distribution of
      comparable interactions found in (a) high resolution kinase complexes (<= 1.8A)
      from the PDB and (b) more generic, small molecule crystal structures from the
      CSD.

PMID- 21075030
TI  - Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on
      insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women.
AB  - OBJECTIVE: Insulin-like growth factor-1 (IGF-1) is essential for the pubertal
      growth spurt and for normal mammary gland development. IGF-1 increases
      premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in
      most women. The endogenous estrogens and their metabolites also influence IGF-1
      levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We
      aimed to study IGF-1 levels and body size in relation to GSTM1 and GSTT1
      deletions, and GSTP1*1B and current oral contraceptive (OC) status. DESIGN:
      Questionnaires on reproductive factors and OC use were completed and blood
      samples were obtained during menstrual cycle day 18-23 in healthy women (<=40
      years) from breast cancer high-risk families. IGF-1 was analyzed with
      radioimmunoassay. Genetic analyses were done with PCR based methods. Initially
      258 women were included. After exclusion 229 women were finally included in the
      analyses of IGF-1 in relation to GSTM1 and GSTT1. RESULTS: Among the 142 non-OC
      users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with lower IGF-1 levels
      while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had higher IGF-1 levels
      (P(interaction)=0.024). In the 87 OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were
      associated with higher IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0
      carriers had lower IGF-1 levels (P(interaction)=0.010). Among all 229 women, a
      three-way interaction model showed an interaction between the
      GSTM1*0/*0/GSTT1*0/*0 genotype and OC use on IGF-1 levels (P(interaction)=0.003).
      GSTP1*1B was not associated with IGF-1. The GSTM1*1/GSTT1*0/*0 genotype was
      associated with high body weight (P=0.003) and GSTM1*0/*0/GSTT1*0/*0 was
      associated with early growth (P=0.003). CONCLUSION: Both OC use and GSTT1 and
      GSTM1 genotypes may influence IGF-1 levels. Further studies are warranted to
      confirm our finding and elucidate the clinical importance.

PMID- 21075031
TI  - Ultrasound assisted dehydrogenation of 2-oxo-1,2,3,4-tetrahydropyrimidine-5
      carboxamides.
AB  - Dehydrogenation of various 2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamides
      (THPMs) to 2-oxo-1,2-dihydropyrimidine-5-carboxamides (DHPMs) using
      tetrabutylammonium peroxydisulfate (TBAPS) as an efficient oxidizing agent under
      thermal and sono-thermal conditions has been investigated. In contrast to the
      thermal reaction, a decrease of the amount of oxidant and an increase of the rate
      of reaction are observed by simultaneously applying heat and ultrasound. The
      nature of both C-4 and C-5 substituents on the heterocyclic ring influences the
      rate of reaction under both conditions. The proposed electron-transfer-induced
      dehydrogenation in this study is supported by conductometric studies.

PMID- 21075032
TI  - Targeted computational probabilistic corroboration of experimental knee wear
      simulator: the importance of accounting for variability.
AB  - Experimental testing is widely used to predict wear of total knee replacement
      (TKR) devices. Computational models cannot replace this essential in vitro
      testing, but they do have complementary strengths and capabilities, which make in
      silico models a valuable support tool for experimental wear investigations. For
      effective exploitation, these two separate domains should be closely corroborated
      together; this requires extensive data-sharing and cross-checking at every stage
      of simulation and testing. However, isolated deterministic corroborations provide
      only a partial perspective; in vitro testing is inherently variable, and
      relatively small changes in the environmental and kinematic conditions at the
      articulating interface can account for considerable variation in the reported
      wear rates. Understanding these variations will be key to managing uncertainty in
      the tests, resulting in a 'cleaner' investigation environment for further
      refining current theories of wear. This study demonstrates the value of
      probabilistic in silico methods by describing a specific, targeted corroboration
      of the AMTI knee wear simulator, using rigid body dynamics software models. A
      deterministic model of the simulator under displacement-control was created for
      investigation. Firstly, a large sample of experimental data (N>100) was collated,
      and a probabilistic computational study (N>1000 trials) was used to compare the
      kinetic performance envelopes for in vitro and in silico models, to more fully
      corroborate the mechanical model. Secondly, corresponding theoretical wear-rate
      predictions were compared to the experimentally reported wear data, to assess the
      robustness of current wear theories to uncertainty (as distinct from the
      mechanical variability). The results reveal a good corroboration for the physical
      mechanics of the wear test rig; however they demonstrate that the distributions
      for wear are not currently well-predicted. The probabilistic domain is found to
      be far more sensitive at distinguishing between different wear theories. As such
      we recommend that in future, researchers move towards probabilistic studies as a
      preferred framework for investigations into implant wear.

PMID- 21075033
TI  - Socio-spatial patterns of home care use in Ontario, Canada: a case study.
AB  - Home care is the fastest growing segment of Canada's health care system. Since
      the mid-1990 s, the management and delivery of home care has changed dramatically
      in the province of Ontario. The objective of this paper is to examine the socio
      spatial characteristics of home care use (both formal and informal) in Ontario
      among residents aged 20 and over. Data are drawn from two cycles of the Canadian
      Community Health Survey (CCHS Cycle 3.1 2005 and Cycle 4.1 2007) and are analyzed
      at a number of geographical scales and across the urban to rural continuum. The
      study found that rural residents were more likely than their urban counterparts
      to receive government-funded home care, particularly nursing care services.
      However, rural residents were less likely to receive nursing care that was self
      financed through for-profit agencies and were more reliant on informal care
      provided by a family member. The study also revealed that women and seniors were
      far more dependent on services that they paid for as compared to informal
      services. People with lower incomes and poorer health status, as well as rural
      residents, were also more likely to use informal services. The paper postulates
      that the introduction of managed competition in Ontario's home care sector may be
      effective in more populated parts of the province, including large cities, but at
      the same time may have left a void in access to for-profit formal services in
      rural and remote regions.

PMID- 21075034
TI  - To live and die in L.A. County: neighborhood economic and social context and
      premature age-specific mortality rates among Latinos.
AB  - This ecological study compares the utility of neighborhood economic, social, and
      co-ethnic concentration characteristics in explaining mortality among Latinos
      aged 25-64 due to all causes and heart disease in Los Angeles County from 2000 to
      2004. Results indicate that local economic well-being and social resources are
      beneficial for both outcomes to varying degrees. Economic well-being is the
      strongest predictor of all-cause mortality rates among Latinos aged 25-64 and was
      the only characteristic that significantly predicted heart disease mortality
      among those aged 45-64. Among social resources, results indicate collective
      efficacy is comparatively more important for mortality in younger adults. Social
      interaction was associated with lower mortality but the effect was not
      significant for any outcome. Co-ethnic concentration was consistently associated
      with increased mortality, but only achieved significance for all-cause mortality
      in younger adults. This effect was mediated by neighborhood income. Though social
      resources appear to be beneficial to a lesser extent, results suggest policy
      should first aim to address income disparities across local communities.

PMID- 21075035
TI  - Environmental justice in a French industrial region: are polluting industrial
      facilities equally distributed?
AB  - Recent studies have suggested that minority or deprived groups are subject to the
      additional burden of a polluted living environment. Our goal is to determine
      whether such environmental inequalities occur in France's leading industrial
      region, using detailed socio-economic data and advanced Bayesian methods.
      Associations between proximity to hazardous facilities (i.e., within a 2 km
      radius) and the socio-economic characteristics of populations are analyzed at
      fine geographical scales. Noxious facilities are disproportionately located in
      higher foreign-born communities after controlling for deprivation (Townsend
      score), population density and rural/urban status. High deprivation also appears
      as a predictive factor, although less strongly and less consistently.

PMID- 21075036
TI  - Predictors of mental and physical health: individual and neighborhood levels of
      education, social well-being, and ethnicity.
AB  - This study examines how education benefits health through social well-being in
      Hawaii where the centrality of community life is underscored. The 2007 Hawaii
      Health Survey with linked zip-code information was used to investigate the
      effects of education at both individual and neighborhood levels using mixed
      effects models. Geographic Information System was applied to map the geographical
      distributions of education, social well-being, and health. It was found that
      individual-level education benefits mental health and its effects are largely
      mediated by respondents' employment status and their social well-being (social
      integration, social contribution, social actualization, and social coherence).
      Both individual and neighborhood-level education promotes physical health and
      their effects are partially mediated by economic well-being and two indicators of
      social well-being (social integration and social coherence). Results of this
      study suggest the independent effects of two levels of education on physical
      health and the importance of education and social well-being to both mental and
      physical health in the State of Hawaii.

PMID- 21075037
TI  - A systematic literature review on the effectiveness of non-invasive therapy for
      cervicobrachial pain.
AB  - Cervicobrachial pain is a common cervical spine disorder. It is frequently
      managed through non-invasive therapy. The objective of this systematic review was
      to assess effectiveness of non-invasive therapy for the management of
      cervicobrachial pain, in terms of pain, function and disability. Computerised
      searches were performed to January 2010. Studies were selected using pre
      specified criteria. Methodological quality of included studies was assessed using
      PEDro and level of inter-reviewer agreement reported using Kappa values. Meta
      analyses were conducted on pain scores for similar interventions using
      DerSimonian-Laird random-effects model to allow for heterogeneity. Effect sizes
      and 95% confidence intervals were reported. Qualitative analyses, based on Centre
      for Evidence Based Medicine levels of evidence, were conducted for function and
      disability. Eleven studies were included in the review. Interventions included
      general physiotherapy, cervical traction, manual therapy, exercise therapy, and
      behavioural change approaches. There was inconclusive evidence for the
      effectiveness of non-invasive management of cervicobrachial pain. Potential
      benefits were indicated in the provision of manual therapy and exercise and
      behavioural change approaches to reduce pain. General physiotherapy and traction
      were no more effective than comparators in reducing pain (level A evidence).
      Effects of non-invasive management on function and disability were mixed. Future
      studies should identify which sub-groups of cervicobrachial pain respond to
      specific interventions.

PMID- 21075038
TI  - Effect of pilates mat exercises and conventional exercise programmes on
      transversus abdominis and obliquus internus abdominis activity: pilot randomised
      trial.
AB  - Pilates training is said to increase Transversus abdominis (TrA) and Obliquus
      internus (OI) activation during exercise and functional activities. 34 Pain-free
      health club members with no Pilates experience, mean (SD) age 30(7) years, were
      randomised to Pilates mat exercises or strength training. Participants exercised
      unsupervised twice-weekly for eight weeks. TrA and OI thickness (a proxy for
      muscle activity at the low-medium efforts of our exercises) were measured with
      ultrasound pre- and post-training during Pilates exercises 'Imprint' (an
      abdominal drawing-in manoeuvre) and 'Hundreds A' (lying supine, arms slightly
      raised, hips and knees flexed to 90 degrees ) and 'Hundreds B' (as A, with neck
      flexion) and functional postures sitting and standing. Pilates participants had
      increased TrA thickness in Hundreds A [all values mean (SD) mm]: 3.7(1.3) pre
      intervention, 4.7(1.1) post-intervention (P = 0.007); and decreased OI muscle
      thickness during Imprint: 11.7(2.8) pre-intervention, 10.8(3.5) post-intervention
      (P = 0.008). Strength training participants had greater OI thickness during
      Imprint (P = 0.014), Hundreds A (P = 0.018) and Hundreds B (P = 0.004) than
      Pilates participants post-intervention. There were no changes in muscle thickness
      at rest or during functional postures. Pilates training appears to increase TrA
      activity but only when performing Pilates exercises. Further research is required
      into Pilates in clinical populations and how to increase deep abdominal
      activation during functional activities.

PMID- 21075039
TI  - IL-17 and Th17 cells in tuberculosis.
AB  - Tuberculosis is primarily a disease of the lung. Constant expression of cellular
      immunity in this organ is required to control Mycobacterium tuberculosis growth,
      but this can also result in chronic inflammation and pathologic consequences.
      During primary tuberculosis both IFN-gamma and IL-17 are induced: both are potent
      inflammatory cytokines capable of inducing expression of chemokines that promote
      cell recruitment and granuloma organization throughout infection. During the
      chronic phase, a balance between Th1 and Th17 responses needs to be achieved to
      control bacterial growth and limit immunopathology, as a shift of the response
      towards excessive IL-17 production may sustain extensive neutrophil recruitment
      and tissue damage. Thus, regulation of Th1 and Th17 responses during tuberculosis
      is essential to promote anti-mycobacterial immunity and prevent extensive
      immunopathological consequences.

PMID- 21075041
TI  - Th17 cytokines: the good, the bad, and the unknown.

PMID- 21075040
TI  - C-type lectins, fungi and Th17 responses.
AB  - Th17 cells are a recently discovered subset of T helper cells characterised by
      the release of IL-17, and are thought to be important for mobilization of immune
      responses against microbial pathogens, but which also contribute to the
      development of autoimmune diseases. The identification of C-type lectin receptors
      which are capable of regulating the balance between Th1 and Th17 responses has
      been of particular recent interest, which they control, in part, though the
      release of Th17 inducing cytokines. Many of these receptors recognise fungi, and
      other pathogens, and play key roles in driving the development of protective anti
      microbial immunity. Here we will review the C-type lectins that have been linked
      to Th17 type responses and will briefly examine the role of Th17 responses in
      murine and human anti-fungal immunity.

PMID- 21075042
TI  - Interleukin 17 in vascular inflammation.
AB  - Interleukin (IL)-17 (also known as IL-17A) is produced by activated T cells. It
      is a marker cytokine of the T(H17) lineage. IL-17 production is induced in
      infections, autoimmune diseases and other inflammatory events. IL-17 is involved
      in host defense, but also inflammatory tissue destruction. Vascular disease,
      mostly in the chronic form of atherosclerosis, is a leading cause of death. While
      normal vessels harbor only few leukocytes, large numbers of both innate and
      adaptive immune cells accumulate during vascular inflammation, both in chronic
      forms such as atherosclerosis and in acute vasculitis. IL-17 has a role in
      chronic vascular inflammation of atherosclerosis and possibly hypertensive
      vascular changes. In acute inflammation, IL-17 is elevated and may be causally
      involved in the autoimmune vasculitides including vasculitis in systemic lupus
      erythematodes. Blood vessels are important targets in alloimmune graft rejection
      and a number of studies provide data on a role of IL-17 in this context. This
      brief review summarizes the currently available evidence for and putative
      mechanisms of action of IL-17 in mouse models of and human vascular disease.

PMID- 21075043
TI  - Redox platforms in cancer drug discovery and development.
AB  - Redox homeostasis is frequently dysregulated in human disease, particularly
      cancer. Recent and ongoing efforts seek to validate and extend this platform for
      the discovery/development of anticancer drugs. As the primary source of cellular
      redox buffer, thiols (in particular glutathione) have been therapeutically
      targeted in cancer treatment, myeloproliferation, hematopoietic progenitor cell
      mobilization and immune response. A number of 'redox modulating' drugs have been,
      or are, under development and the pipeline seems viable. Moreover, S
      glutathionylation is a protein post-translational modification that influences a
      number of critical cell pathways and in the medium term, defining the
      'glutathionome' has the possibility to provide opportunities for target
      identification for therapeutic intervention perhaps with a relevance that
      parallels ongoing efforts with the kinome.

PMID- 21075044
TI  - Redox cycling compounds generate H2O2 in HTS buffers containing strong reducing
      reagents--real hits or promiscuous artifacts?
AB  - Redox cycling compounds (RCCs) generate MUM concentrations of hydrogen peroxide
      (H(2)O(2)) in the presence of strong reducing agents, common buffer components
      used to maintain the catalytic activity and/or folding of target proteins for
      high throughput screening (HTS) assays. H(2)O(2) generated by RCCs can indirectly
      inhibit the catalytic activity of proteins by oxidizing accessible cysteine,
      tryptophan, methionine, histidine, or selenocysteine residues, and indeed several
      important classes of protein targets are susceptible to H(2)O(2)-mediated
      inactivation; protein tyrosine phosphatases, cysteine proteases, and
      metalloenzymes. The main sources of H(2)O(2) in cells are the Nox enzyme/SOD
      systems, peroxisome metabolism, and the autoxidation of reactive chemicals by
      enzyme mediated redox cycling at both the microsomal and mitochondrial sites of
      electron transport. Given the role of H(2)O(2) as a second messenger involved in
      the regulation of many signaling pathways it is hardly surprising that compounds
      that can generate intracellular H(2)O(2) by enzyme mediated redox cycling would
      have pleiotropic effects. RCCs can therefore have serious negative consequences
      for the probe and/or lead generation process: primary HTS assay hit rates may be
      inflated by RCC false positives; crucial resources will be diverted to develop
      and implement follow up assays to distinguish RCCs from real hits; and screening
      databases will become annotated with the promiscuous activity of RCCs. In an
      attempt to mitigate the serious impact of RCCs on probe and lead generation, two
      groups have independently developed assays to indentify RCCs.

PMID- 21075045
TI  - hMLH1 promoter methylation is an early event in oral cancer.
AB  - Promoter methylation is believed to inactivate the expression of hMLH1. This
      process has been implicated in the tumorigenesis of oral squamous cell carcinoma
      (OSCC). Thus, the aim of this study was to determine the profile of hMLH1
      methylation and protein expression in OSCC. The matched case-control study
      included 50 OSCC cases and 200 controls, with a median of age 64 (Q1-Q3 54-71)
      years. Protein expression was determined by immunohistochemical staining, and
      hMLH1 gene promoter methylation was analyzed by methylation-specific polymerase
      chain reaction (MSP). A conditional logistic regression model for risk factors
      was built for OSCC cases and matched controls. Promoter methylation of hMLH1 was
      detected in 38 (76%) OSCC cases, but in none of the control samples. Of the 38
      OSCC samples with promoter methylation, 12 (32%) were negative for hMLH1 protein,
      and corresponded to early clinical stages (10 in stage II and 2 in stage I). All
      12 unmethylated samples showed positive stain for hMLH1. Multiple logistic
      regression analysis showed an OR of 16.54 (IC 95%: 1.69-161.68, p=0.016) for
      methylation of the hMLH1 gene and early stages of OSCC, adjusting by gender and
      tobacco use. This study showed a high frequency of hMLH1 promoter methylation
      that occurred in most of the early stage cases and in about half of the late
      stage cases. It is proposed that hMLH1 promoter methylation is an early event
      that is maintained during tumor progression.

PMID- 21075046
TI  - Processing bodies and plant development.
AB  - Processing bodies (P-bodies) contain RNA-protein complexes linked to cytoplasmic
      RNA decay pathways including mRNA decapping, nonsense-mediated decay (NMD) and
      small RNA-mediated decay. Plants deficient in P-body components display severe
      developmental perturbations, suggesting that these cytoplasmic bodies play
      important roles in regulating gene expression during plant development. Here, we
      summarize recent progress in the genetic dissection of P-body components and
      their roles in translational repression and mRNA decapping.

PMID- 21075047
TI  - Volvox: simple steps to developmental complexity?
AB  - Volvox, Chlamydomonas, and their close relatives - collectively the volvocine
      green algae - comprise an excellent system for investigating the origins of
      developmental complexity. Over a relatively short period of time Volvox evolved
      an impressive suite of developmental traits, including asymmetric cell division,
      multicellularity with germ-soma division of labor, embryonic morphogenesis, and
      oogamy. Recent molecular genetic analyses of important developmental genes and
      comparative analyses of the fully sequenced Volvox and Chlamydomonas genomes have
      provided important insights into how these and other traits came to be.
      Surprisingly, the acquisition of much of the developmental innovation in this
      family seems to have involved relatively minor tinkering with the ancestral
      unicellular blueprint.

PMID- 21075048
TI  - Cutaneous perception during tDCS: role of electrode shape and sponge salinity.

PMID- 21075049
TI  - The EMG needle goes deeper in ALS.

PMID- 21075050
TI  - New insights into galactose metabolism by Schizosaccharomyces pombe: isolation
      and characterization of a galactose-assimilating mutant.
AB  - The fission yeast Schizosaccharomyces pombe cannot use galactose as a carbon or
      energy source, and little is known about galactose metabolism in this species.
      Here we report isolation of a galactose-assimilating mutant that grows on a
      medium containing galactose as a sole carbon source through use of a proofreading
      deficient DNA polymerase delta variant encoded by cdc6-1. Based on comparative
      analysis of gene expression profiles in the wild-type and the mutant (FG2-8), we
      found that SPBPB2B2.10c (gal7+), SPBPB2B2.12c (gal10+) and SPBPB2B2.13 (gal1+),
      homologous to Saccharomyces cerevisiae GAL7, GAL10 and GAL1, respectively, and
      SPBPB2B2.08, SPBPB2B2.09c, and SPBPB2B2.11 that localize close to the gal genes,
      were highly expressed and dramatically induced by addition of galactose. The
      gal7Delta strain, carrying an integrated ura4+ marker at the gal7+ locus, grew on
      5-fluoroorotic acid (5-FOA)-containing medium. In contrast, the FG2-8 gal7Delta
      strain could not grow on 5-FOA medium. In addition, expression of gal7+,
      SPBPB2B2.13, gal10+ and gal1+ genes increased in the wild-type strain when
      carried on a vector, and these transformants grew on galactose medium. We suggest
      that gal7+, gal10+, and gal1+ are localized close to a chromosomal terminal
      repressed by gene silencing in S. pombe. In contrast, gene silencing was
      defective in the FG2-8 strain making galactose assimilation possible.

PMID- 21075051
TI  - Coagulase-positive Staphylococcus pseudintermedius from animals causing human
      endocarditis.
AB  - We report a case of infection with coagulase-positive Staphylococcus
      pseudintermedius related to the implantation of a cardioverter-defribrillator
      device. This species is usually isolated from infected animals, and contact with
      a dog was the probable source of infection in this patient. This isolate produced
      a leukotoxin effective against human polymorphonuclear leukocytes.

PMID- 21075052
TI  - Cardiac surgery in the presence of dialysis: effect on mid-term outcomes and
      quality of life.
AB  - BACKGROUND: this study evaluates the impact on short and mid-term outcomes and
      quality of life of dialysis dependent patients undergoing cardiac surgery. The
      benefit to patients from a bio-psycho-social perspective is put into context via
      an inter-personal patient interview. METHODS: the study period was from February
      1999 to February 2009. Data on 45 dialysis dependent patients undergoing cardiac
      surgery was prospectively collected and analysed retrospectively. The mean age
      was 59.9 years and sex ratio (M:F) of 32:13. All patients were New York Heart
      Association (NYHA) class >2 preoperatively. Fifty-five percent (25/45) of these
      patients had coronary artery bypass graft surgery (CABG) and 28% (12/45) aortic
      valve replacement surgery alone. Forty-two variables were studied to define
      predictors of outcome. Follow-up was 100% (18/18) with a mean follow-up time of
      48.1 months (0-124 months). They were followed up with quality of life and
      functional coping score surveys (SF-36). RESULTS: the main postoperative
      morbidities were pulmonary complications 20% (9/45), multi-organ failure 11%
      (5/45) and blood transfusion rates 40% (18/45). The 30 day mortality of the
      dialysis patients was 13.3% (6/45) and late death was 54% (21/39). Increasing
      age, pulmonary complications and blood product usage were the significant
      predictors of both 30 day mortality (age: p=0.02, pulmonary: p=0.003, blood
      product usage: p=0.03) and late death (age: p=0.008, pulmonary: p=0.02, blood
      product usage: p=0.02). New York Heart Association class was I-II in 83% (15/18)
      on long term follow up. All five patients awaiting renal transplants received
      their transplant in the first six months post-operatively. The overall survival
      at one year was 78% and five years was 40%. On SF-36 health questionnaire all
      patients scored less on physical functioning than the Australian norms (24.89 +/-
      4.10). CONCLUSIONS: cardiac surgery in the presence of renal failure is
      associated with significant morbidity and mortality. The overall survival and
      quality of life of dialysis patients undergoing cardiac surgery is poor.

PMID- 21075053
TI  - HPV-based cervical-cancer screening in China.

PMID- 21075054
TI  - Performance of high-risk human papillomavirus DNA testing as a primary screen for
      cervical cancer: a pooled analysis of individual patient data from 17 population
      based studies from China.
AB  - BACKGROUND: Controversy remains over whether high-risk human papillomavirus (HPV)
      DNA testing should be used as a primary screen for cervical cancer. The aims of
      our study were to assess whether HPV DNA testing could be applied to cervical
      cancer screening programmes in China, as well as other similar developing
      countries. METHODS: We did a pooled analysis of population-based cervical cancer
      screening studies done in mainland China from 1999 to 2008 with concurrent HPV
      DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based
      cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were
      sexually active, not pregnant, had an intact uterus, and had no history of
      cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation.
      All women positive for any test were referred for colposcopy and biopsy. Cervical
      lesions were diagnosed by directed or random biopsy. We assessed the diagnostic
      accuracy of HPV DNA testing for the detection of CIN grade 3 or greater.
      FINDINGS: 30,371 women from 17 cross-sectional, population-based studies in
      various parts of China were screened. 1523 women were subsequently excluded
      because of inadequate HPV DNA specimens or they did not have a biopsy taken,
      which included women with atypical squamous cells of undetermined significance;
      low-grade squamous intraepithelial lesion or worse; positive HPV, negative
      cytology, and missing or positive colposcopy results; and unsatisfactory cytology
      results. HPV DNA testing had a higher sensitivity of 97.5% (95% CI 95.7-98.7) for
      detection of CIN grade 3 or worse, and a lower specificity of 85.1% (82.3-87.9),
      compared with cytology (sensitivity 87.9% [95% CI 84.7-90.7], specificity 94.7%
      [93.5-96.0]) and VIA (54.6% [48.0-61.2], 89.9% [86.8-93.0]). Sensitivity did not
      vary by study or age (<35 years, 35-49 years, >=50 years); however, specificity
      did vary with age (p<0.0001) and was highest in women younger than 35 years
      (89.4%; 95% CI 86.1-91.5). An increase in the positive cutoff point from the
      manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV
      DNA positivity from 16.3% to 13.9% (p<0.0001), which could result in a decrease
      in referral rates, although sensitivity was slightly lower (97.5% to 95.2%). An
      increase in the cutoff point to 10 pg/mL in women younger than 35 years
      maintained a high sensitivity 97.7% (95% CI 87.7-99.9) and increased specificity
      to 93.5% (95% CI 91.9-94.6). INTERPRETATION: HPV DNA testing is highly sensitive
      and moderately specific for CIN grade 3 or worse, with consistent results across
      study sites and age groups-including women younger than 35 years. A rise in the
      cutoff point might be beneficial for future screening programmes in China,
      especially when screening women younger than 35 years.

PMID- 21075055
TI  - Vision from the right stem.
AB  - Cultures of limbal cells are a safe and effective treatment for the destruction
      of the human cornea owing to chemical burns. The essential feature of the graft
      is the presence of an adequate number of stem cells, which can be determined by
      the expression of the p63 transcription factor. Here, we will discuss the general
      principles defining the rigorous criteria for graftable limbal cultures in light
      of their clinical performances. Such criteria might prove relevant to the future
      therapeutic use of any cultured cell type. 

PMID- 21075056
TI  - Factors affecting transmission of mucosal human papillomavirus.
AB  - Human papillomavirus (HPV) is the most common sexually transmitted infection. The
      effect of HPV on public health is especially related to the burden of anogenital
      cancers, most notably cervical cancer. Determinants of exposure to HPV are
      similar to those for most sexually transmitted infections, but determinants of
      susceptibility and infectivity are much less well established. Gaps exist in
      understanding of interactions between HPV, HIV, and other sexually transmitted
      infections. The roles of mucosal immunology, human microbiota at mucosal
      surfaces, host genetic factors and hormonal concentrations on HPV susceptibility
      and infectivity are poorly understood, as are the level of effectiveness of some
      primary or secondary preventive measures other than HPV vaccination (such as
      condoms, male circumcision, and combination antiretroviral therapy for HIV).
      Prospective couples studies, studies focusing on mucosal immunology, and in-vitro
      raft culture studies mimicking HPV infection might increase understanding of the
      dynamics of HPV transmission.

PMID- 21075058
TI  - Planning extent of resection in epilepsy: limited versus large resections.
AB  - Aggressive versus limited resection is an often-debated topic in epilepsy
      surgery. There are two inherent questions within this debate: (1) Can a more
      limited resection yield seizure freedom rates similar to those afforded by
      wider/more aggressive resection, with lower rates of neurological complications?
      (2) Does wider/more aggressive resection increase seizure freedom rates, with
      tolerable neurological complications rates? Further, if more limited resection
      has a lower seizure freedom rate, but fewer complications, is quality of life
      better or worse than that following a wider/more aggressive resection that
      increases seizure freedom rate but yields a higher complication rate? Here, we
      review the literature to address these questions. Because most studies are
      retrospective observational studies, with limited statistical power to draw
      strong conclusions, there is a need for more randomized prospective multicenter
      clinical trials incorporating advances in technique for identifying the seizure
      onset zone (e.g., subtractive ictal SPECT) and tissue at risk (e.g., diffusion
      tensor imaging) to inform this discussion.

PMID- 21075057
TI  - Meningococcal carriage by age: a systematic review and meta-analysis.
AB  - BACKGROUND: Neisseria meningitidis is an important cause of meningitis and
      septicaemia, but most infected individuals experience a period of asymptomatic
      carriage rather than disease. Previous studies have shown that carriage rates
      vary by age and setting; however, few have assessed carriage across all ages. We
      aimed to estimate the age-specific prevalence of meningococcal carriage. METHODS:
      We searched Embase, Medline, Web of Science, the Cochrane Library, and grey
      literature for papers reporting carriage of N meningitidis in defined age groups
      in European countries or in countries with a similar epidemiological pattern
      (where disease caused by serogroups B and C predominates). We used mixed-effects
      logistic regression with a natural cubic spline to model carriage prevalence as a
      function of age for studies that were cross-sectional or serial cross-sectional.
      The model assessed population type, type of swab used, when swabs were plated,
      use of preheated plates, and time period (decade of study) as fixed effects, with
      country and study as nested random effects (random intercept). FINDINGS: Carriage
      prevalence increased through childhood from 4.5% in infants to a peak of 23.7% in
      19-year olds and subsequently decreased in adulthood to 7.8% in 50-year olds. The
      odds of testing positive for carriage decreased if swabs were not plated
      immediately after being taken compared with if swabs were plated immediately
      (odds ratio 0.46, 95% CI 0.31-0.68; p = 0.0001). INTERPRETATION: This study
      provides estimates of carriage prevalence across all ages, which is important for
      understanding the epidemiology and transmission dynamics of meningococcal
      infection. FUNDING: None.

PMID- 21075059
TI  - A comprehensive neuropsychological profile of women with psychogenic nonepileptic
      seizures.
AB  - The purpose of this study was to compare the neuropsychological profile of women
      with VEEG-confirmed diagnoses of psychogenic nonepileptic seizures (PNES) with
      that of an age- and education-matched group of women with left temporal lobe
      epilepsy (LTLE). Results indicate that in a relatively homogenous PNES sample, no
      severe neurocognitive impairments were present, further supporting a
      psychologically versus neurologically driven pathology of PNES. In comparison to
      age-stratified normative data, the PNES group demonstrated only a modest
      deficiency across neuropsychological domains and a relative area of weakness in
      attention and working memory, and generally outperformed their counterparts with
      LTLE. Although the attentional deficits in the PNES group may have been
      influenced by their elevated levels of emotional distress, symptoms of depression
      and anxiety were significant and common in both patients with PNES and those with
      LTLE, and therefore, the utility of psychological factors in discriminating these
      groups is limited. The present findings warrant the use of longitudinal research
      with patients with PNES to identify changes in the presentation of this condition
      as well as its subsequent neurocognitive and emotional impairments.

PMID- 21075060
TI  - Metabolomic changes in autopsy-confirmed Alzheimer's disease.
AB  - BACKGROUND: Metabolomics, the global science of biochemistry, provides powerful
      tools to map perturbations in the metabolic network and enables simultaneous
      quantification of several metabolites to identify metabolic perturbances that
      might provide insights into disease. METHODS: In this pilot study, we took a
      targeted electrochemistry-based metabolomics approach where liquid chromatography
      followed by coulometric array detection enables quantification of over 30
      metabolites within key neurotransmitter pathways (dopamine and serotonin) and
      pathways involved in oxidative stress. RESULTS: Using samples from postmortem
      ventricular cerebrospinal fluid (15 Alzheimer's disease [AD] and 15 nondemented
      subjects with autopsy-confirmed diagnoses) and by using regression models,
      correlations, Wilcoxon rank-sum tests, and t-tests we identified alterations in
      tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD.
      Reductions in norepinephrine and its related metabolites were also seen,
      consistent with previously published data. CONCLUSIONS: These data support
      further investigation of metabolomics in larger samples of clinical AD as well as
      in those with preclinical disease for use as biomarkers.

PMID- 21075061
TI  - What Latino Puerto Ricans and non-Latinos say when they talk about Alzheimer's
      disease.
AB  - BACKGROUND: To discover whether Latino Puerto Rican and non-Latino communities
      differ in the words they use to talk about Alzheimer's disease (AD). METHODS:
      Four groups of 30 persons per group defined by self-identified ethnicity and
      caregiver status: Latino Puerto Ricans and non-Latino Whites, who were either
      caregivers or non-caregivers completed free-listing exercises to identify the
      words they use when they describe AD causes, symptoms, caregiving, and research
      risks and benefits. RESULTS: Both Latino Puerto Ricans and non-Latino Whites
      recognize AD as a disease of memory loss and other cognitive problems. Although
      both groups used the term "sadness" to describe AD, non-Latino Whites did not
      feature emotional, behavioral, or psychological problems as among the causes of
      AD. Although all the groups' descriptions of a person who lives with and cares
      for a person with AD shared the word "loving," Latino Puerto Ricans focused on a
      good spouse who exercises intelligence, patience, and attention on behalf of the
      person with AD and did not use the term "caregiver." In contrast, non-Latino
      Whites typically used the term "caregiver." Both groups' lists shared words that
      describe research as presenting harms to an AD patient and requiring a commitment
      of time. Latino Puerto Ricans' lists suggested an understanding of research
      benefits akin to clinical care. CONCLUSIONS: Notable differences exist in how
      Latino Puerto Ricans and non-Latino Whites talk about AD and AD research.
      Clinicians, clinical investigators, and patient educators need to consider these
      differences when they conduct clinical care and research and design outreach and
      educational materials.

PMID- 21075062
TI  - Safety, efficacy and convenience of tobramycin inhalation powder in cystic
      fibrosis patients: The EAGER trial.
AB  - BACKGROUND: A light-porous-particle, dry-powder formulation of tobramycin was
      developed, using PulmoSphere(r) technology, to improve airway delivery
      efficiency, substantially reduce delivery time, and improve patient convenience
      and satisfaction. We evaluated the safety, efficacy and convenience of tobramycin
      inhalation powder (TIPTM) versus tobramycin inhalation solution (TIS, TOBI(r))
      for treating Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients
      aged >=6 years. METHODS: In this open-label study, 553 patients were randomized
      3:2 to TIP (total 112mg tobramycin) via the Novartis T-326 Inhaler or TIS
      300mg/5mL via PARI LC(r) PLUS nebulizer twice daily for three treatment cycles
      (28 days on-drug, 28 days off-drug). Safety, efficacy, and treatment satisfaction
      outcomes were evaluated. RESULTS: TIP was generally well-tolerated; adverse
      events were similar in both groups. The rate of cough suspected to be study drug
      related was higher in TIP-treated patients (TIP: 25.3%; TIS: 4.3%), as was the
      overall discontinuation rate (TIP: 26.9%; TIS: 18.2%). Increases in FEV(1)%
      predicted from baseline to Day 28 of Cycle 3 were similar between groups; the
      mean reduction in sputum P. aeruginosa density (log(10) CFU/g) on Day 28 of Cycle
      3 was also comparable between groups. Administration time was significantly less
      for TIP (mean: 5.6 versus 19.7min, p<0.0001). Treatment satisfaction was
      significantly higher for TIP for effectiveness, convenience, and global
      satisfaction. CONCLUSIONS: TIP has a safety and efficacy profile comparable with
      TIS, and offers a far more convenient treatment option for pseudomonas lung
      infection in CF.

PMID- 21075063
TI  - Disposable versus reusable jet nebulizers for cystic fibrosis treatment with
      tobramycin.
AB  - BACKGROUND: Jet nebulizers are commonly used to administer aerosolized tobramycin
      to CF patients. The aim of this study was to assess the performance of disposable
      jet nebulizers as an alternative to reusable nebulizers such as the Pari LC Plus.
      METHOD: From a survey conducted in 49 CF centers in France, 18 disposable jet
      nebulizer systems were selected. An in vitro study was performed with 20 jet
      nebulizer/air source combinations (18 disposable and 2 reusable) to determine
      their performance with tobramycin solution (300 mg/5 mL). A scintigraphic
      deposition study in baboons was performed to validate the in vitro data. RESULTS:
      In vitro and in vivo results correlated. There was no overall relationship
      between the compressed air source and nebulizer performance, but the nebulizer
      interface was responsible for significantly different results. CONCLUSIONS: None
      of the disposable nebulizers tested in this study can be recommended as an
      alternative to the Pari LC Plus nebulizer for tobramycin.

PMID- 21075065
TI  - Non-invasive prenatal diagnosis by fetal nucleic acid analysis in maternal
      plasma: the coming of age.
AB  - Prenatal diagnosis is an important part of obstetrics care. In the current
      prenatal programmes, definitive diagnosis of fetal genetic or chromosomal
      conditions is conducted through fetal sampling by amniocentesis or chorionic
      villus sampling. To obviate the risks of fetal miscarriage that are associated
      with the invasive sampling procedures, we have been developing non-invasive
      prenatal diagnostic tests based on cell-free fetal DNA analysis from maternal
      plasma. To date, fetal sex and rhesus D status determination by circulating fetal
      DNA analysis is performed clinically in many centres. Strategies for the non
      invasive diagnosis of monogenic diseases have been developed. Accurate detection
      of fetal trisomy 21 by next-generation sequencing has been achieved. Many of the
      non-invasive prenatal tests could be introduced to the clinics as soon as cost
      effective and high throughput protocols are developed.

PMID- 21075066
TI  - Reply to: Guidelines for reconstruction of the eyelids and canthal regions. J
      Plast Reconstr Aesthet Surg 2010;63(9):1420-1433.

PMID- 21075067
TI  - Comparison of auscultatory and echocardiographic findings in healthy adult cats.
AB  - OBJECTIVES: This pilot study was performed to investigate murmur prevalence and
      to explore the association between auscultatory and echocardiographic findings in
      apparently healthy cats in order to design a larger study. ANIMALS, MATERIALS AND
      METHODS: Adult cats in 4 rehoming centres were screened by auscultation and
      echocardiography (echo) over 2 periods of 2 weeks each. In the first period, echo
      was attempted only in cats with murmurs. In the second period, all cats underwent
      auscultation by 2 observers and echo. LVH was defined in 5 ways: maximal
      diastolic left ventricular (LV) wall thickness >= 6 mm or >= 5.5 mm with 2D
      (LVH(6 2D), LVH(5.5 2D), respectively) or M-Mode echo (LVH(6 MM) or LVH(5.5 MM)
      respectively), or LV wall thickness >= 6 mm (2D) for >50% of a wall segment
      (LVH(50%)). RESULTS: 67/199 (34%) cats had a murmur. Interobserver agreement on
      murmur presence was moderate (kappa 0.47). 61 cats with a murmur and 31 cats
      without underwent both auscultation and echo. Depending on the criteria, LVH was
      present in 31 (LVH(6 2D)), 21 (LVH(50%)) and 11 (LVH(6 MM)) scanned cats. 18-62%
      of cats with murmurs had LVH, depending on the echo criteria used. Agreement was
      best between observers in identifying LVH using LVH(6 2D) and LVH(50%) (kappa =
      1.0). CONCLUSIONS: Heart murmurs are common in apparently healthy cats. The
      prevalence of LVH varies depending on the criteria used.

PMID- 21075068
TI  - SMAD7 and MGMT genotype variants and cancer incidence in the European Prospective
      Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.
AB  - PURPOSE: The SMAD7 gene was recently identified to be associated with colorectal
      cancer risk. Smad7 protein is a known inhibitor of TGF-beta signalling pathway
      which has a prominent role in tumorigenesis. MGMT gene regulates the direct
      damage reversal repair pathway, preventing DNA damage and potential cancer
      development. This exploratory study aims to investigate the association between
      SMAD7 (rs4464148, rs4939827) and MGMT (rs12917, rs2308321) genotype variants, and
      all-cancer incidence. METHODS: Our study population was a sub-cohort of the EPIC
      Norfolk study, a prospective cohort of approximately 25,000 men and women aged 40
      79. Between recruitment 1993-1997 and follow-up to 2006, 192 incident cases and
      1155 non-cases with genotype data were identified. Baseline 7-day food diary and
      health/lifestyle questionnaire data were analysed. RESULTS: SMAD7 rs4464148
      variant genotype was associated with increased cancer incidence [HR=1.34,
      95%CI=1.00-1.80] but no overall association for SMAD7 rs4939827 or MGMT
      genotypes. Participants with variant genotypes in both SMAD7 SNPs had a higher
      cancer incidence compared to those without any (HR=2.74, 95%CI=1.10-6.79)
      (P=0.03; P(trend)=0.01). Amongst the younger age participants (<mean 62 years),
      SMAD7 rs4464148 variant genotype group had higher HR of 1.71 (95%CI=1.03-2.83)
      compared to the non-variant genotype group. CONCLUSIONS: These findings suggest
      that SMAD7 rs4464148 common variant genotype is associated with cancer incidence
      but not SMAD7 rs4939827, MGMT rs12917 or MGMT rs2308321. A combination of
      variants of the SMAD7 SNPs may be associated with increased cancer risk in this
      study population. However, these findings need to be replicated in larger studies
      and in studies of specific cancer sites.

PMID- 21075072
TI  - TAp63 plays compensatory roles in p53-deficient cancer cells under genotoxic
      stress.
AB  - p53, p63, and p73 belong to the p53 family of proteins, which mediate
      development, differentiation, and various other cellular responses. p53 is
      involved in many anti-cancer mechanisms, such as cell cycle regulation,
      apoptosis, and the maintenance of genomic integrity. The p63 gene is controlled
      by two promoters that direct the expression of two isoforms, one with and one
      without transactivating properties, known as TAp63 and DeltaNp63. In this study,
      p53-deficient cells (Hep3B and PC-3) and p53-expressing cells (A549 and HepG2)
      were treated with doxorubicin to examine the possible roles of TAp63 in these
      cells under genotoxic stress; TAp63 expression was induced in p53-deficient cell
      lines, but not in p53-expressing cell lines. The ectopic expression of p53 in p53
      deficient cells (Hep3B) reduced TAp63 promoter activity, and knockdown of TAp63
      attenuated doxorubicin-induced cell growth arrest by promoting cell cycle
      progression, leading to an increase in the percentage of G(2)/M cells. Moreover,
      knockdown of TAp63 increased cell sensitivity to doxorubicin-induced genomic
      damage. Our results suggest that TAp63 may play a compensatory role in cell cycle
      regulation and DNA damage repair in p53-deficient cancer cells.

PMID- 21075070
TI  - Molecular probes of the mechanism of cytochrome P450. Oxygen traps a substrate
      radical intermediate.
AB  - The diagnostic substrate tetramethylcyclopropane (TMCP) has been reexamined as a
      substrate with three drug- and xenobiotic-metabolizing cytochrome P450 enzymes,
      human CYP2E1, CYP3A4 and rat CYP2B1. The major hydroxylation product in all cases
      was the unrearranged primary alcohol along with smaller amounts of a rearranged
      tertiary alcohol. Significantly, another ring-opened product, diacetone alcohol,
      was also observed. With CYP2E1 this product accounted for 20% of the total
      turnover. Diacetone alcohol also was detected as a product from TMCP with a
      biomimetic model catalyst, FeTMPyP, but not with a ruthenium porphyrin catalyst.
      Lifetimes of the intermediate radicals were determined from the ratios of
      rearranged and unrearranged products to be 120, 13 and 1ps for CYP2E1, CYP3A4 and
      CYP2B1, respectively, corresponding to rebound rates of 0.9*10(10)s(-1),
      7.2*10(10)s(-1) and 1.0*10(12)s(-1). For the model iron porphyrin, FeTMPyP, a
      radical lifetime of 81ps and a rebound rate of 1.2*10(10)s(-1) were determined.
      These apparent radical lifetimes are consistent with earlier reports with a
      variety of CYP enzymes and radical clock substrates, however, the large amounts
      of diacetone alcohol with CYP2E1 and the iron porphyrin suggest that for these
      systems a considerable amount of the intermediate carbon radical is trapped by
      molecular oxygen. These results add to the view that cage escape of the
      intermediate carbon radical in [Fe(IV)-OH ()R] can compete with cage collapse to
      form a C-O bond. The results could be significant with regard to our
      understanding of iron-catalyzed C-H hydroxylation, the observation of P450
      dependent peroxidation and the development of oxidative stress, especially for
      CYP2E1.

PMID- 21075073
TI  - Niemann-Pick type C fibroblasts have a distinct microRNA profile related to lipid
      metabolism and certain cellular components.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at post
      transcriptional level. Dysregulation of miRNA expression may lead to severe
      pathophysiologies in human cells. Niemann-Pick type C (NPC) disease is a complex
      lipid storage disease characterized by late endosomal-lysosomal accumulation of
      multiple lipid molecules. Our aim was to characterize the miRNA profile in NPC
      fibroblasts as they may play an active role in the NPC disease associated changes
      in the cellular physiology. To investigate the miRNA expression, total RNAs were
      isolated from cultured human NPC fibroblasts and healthy fibroblasts and then,
      TaqMan Low-Density Array system containing 365 mature human miRNAs was used.
      Expression differences between the healthy and NPC cells were detected according
      to the relative quantification values. Target genes were predicted by using three
      different algorithms and classified regarding NPC related biological processes
      and cellular components. We found that three miRNAs, miR-196a, miR-196b and miR
      296 were up-regulated (>3.5-fold increase, p<0.05) whereas 38 miRNAs were
      significantly down-regulated in NPC cells (>3.5-fold decrease, p<0.05). Among
      these non-coding RNAs, miR-98 was the most down-regulated (-33.3-fold) miRNA and
      miR-143, the lipid biosynthesis associated miRNA, had a 20-fold decreased
      expression in the NPC cells. Additionally, gene ontology analyses of the target
      genes suggested a distinct role for each miRNA. Our results show that NPC
      fibroblasts have an altered miRNA expression profile and certain miRNAs have
      importance in disease pathogenesis as well as the therapeutic capacity to correct
      lipid related pathophysiologies in the NPC cells.

PMID- 21075074
TI  - Chlorambucil-sensitive and -resistant lymphoid cells display different responses
      to the histone deacetylase inhibitor, sodium butyrate.
AB  - Clinical chemoresistance is a frequent complication of alkylating agent treatment
      of malignant tumours. Chromatin remodelling using histone deacetylase inhibitors
      (e.g., sodium butyrate, NaBu) may increase target cell chemosensitivity.
      Apoptotic responses and expression of chromatin modifying enzymes in lymphoid
      cell lines, LP-1 and NCI-H929, to chlorambucil (CLB) and/or NaBu were examined in
      this study. NaBu augmented the apoptotic response in CLB-resistant LP-1 cells but
      antagonised it in CLB-sensitive NCI-H929 cells. CLB increased expression of
      methyltransferase I and histone acetyltransferase I in both cell lines while NaBu
      had only small effect. CLB-induced increased gene expression was attenuated by
      NaBu in CLB-sensitive NCI-H929 cells but not in resistant LP-1 cells. These
      results suggest that chromatin modifying agents may have differential effects on
      cells depending on their chemosensitivity.

PMID- 21075075
TI  - Expression of semaphorin 3A and its receptors during mouse corneal development.
AB  - Semaphorin 3A (Sema3A) functions to guide the growth of neurons during
      development, with its effects being mediated by receptor complexes composed of
      neuropilin (Npn) and plexin (Plx) proteins. We have now examined the expression
      of Sema3A and its receptor components Npn1 and PlxA during development of the
      mouse cornea. Sema3A and Npn1 showed similar patterns of expression by
      immunohistofluorescence analysis, with such expression being prominent in the
      corneal epithelium during both embryonic and postnatal development. In contrast,
      PlxA was not expressed in the corneal epithelium until after eye opening between
      postnatal days 12 and 14. Laser capture microdissection followed by reverse
      transcription and polymerase chain reaction analysis also showed that the
      abundance of PlxA mRNA in corneal epithelial cells increased significantly during
      postnatal development, again in association with eye opening. Given that
      atmospheric oxygen is thought to play a role in corneal epithelial
      differentiation and maintenance, our results suggest that the up-regulation of
      PlxA expression in the corneal epithelium during postnatal development is
      triggered by exposure of the cornea to the atmosphere. Furthermore, the newly
      expressed PlxA may contribute to the differentiation of corneal epithelial cells
      by mediating Sema3A signaling.

PMID- 21075076
TI  - Isolation and characterization of portal branch ligation-stimulated Hmga2
      positive bipotent hepatic progenitor cells.
AB  - Hepatic stem/progenitor cells are one of several cell sources that show promise
      for restoration of liver mass and function. Although hepatic progenitor cells
      (HPCs), including oval cells, are induced by administration of certain
      hepatotoxins in experimental animals, such a strategy would be inappropriate in a
      clinical setting. Here, we investigated the possibility of isolating HPCs in a
      portal branch-ligated liver model without administration of any chemical agents.
      A non-parenchymal cell fraction was prepared from the portal branch-ligated or
      non-ligated lobe, and seeded onto plates coated with laminin. Most of the cells
      died, but a small number were able to proliferate. These proliferating cells were
      cloned as portal branch ligation-stimulated hepatic cells (PBLHCs) by the
      limiting dilution method. The PBLHCs expressed cytokeratin19, albumin, and Hmga2.
      The PBLHCs exhibited metabolic functions such as detoxification of ammonium ions
      and synthesis of urea on Matrigel-coated plates in the presence of oncostatin M.
      In Matrigel mixed with type I collagen, the PBLHCs became rearranged into cystic
      and tubular structures. Immunohistochemical staining demonstrated the presence of
      Hmga2-positive cells around the interlobular bile ducts in the portal branch
      ligated liver lobes. In conclusion, successful isolation of bipotent hepatic
      progenitor cell clones, PBLHCs, from the portal branch-ligated liver lobes of
      mice provides the possibility of future clinical application of portal vein
      ligation to induce hepatic progenitor cells.

PMID- 21075077
TI  - Promiscuous activity of ER glucosidase II discovered through donor specificity
      analysis of UGGT.
AB  - In glycoprotein quality control system in the endoplasmic reticulum (ER), UGGT
      (UDP-glucose:glycoprotein glucosyltransferase) and glucosidase II (G-II) play key
      roles. UGGT serves as a glycoprotein folding sensor by virtue of its unique
      specificity to glucosylate glycoproteins at incompletely folded stage. By using
      various UDP-Glc analogues, we first analyzed donor specificity of UGGT, which was
      proven to be rather narrow. However, marginal activity was observed with UDP
      galactose and UDP-glucuronic acid as well as with 3-, 4- and 6-deoxy glucose
      analogues to give corresponding transfer products. Intriguingly, G-II smoothly
      converted all of them back to Man(9)GlcNAc(2), providing an indication that G-II
      has a promiscuous activity as a broad specificity hexosidase.

PMID- 21075078
TI  - The effects of Sp7/Osterix gene silencing in the chondroprogenitor cell line,
      ATDC5.
AB  - Chondrocytes are known to express Sp7/Osterix (Osx) to varying degrees, but the
      role of Osx in chondrocytes is still unknown. In the current study, we
      investigated the role of the Osx gene using the clonal mouse embryonic cell line
      ATDC5, which retains the properties of the chondroprogenitor. ATDC5 cells express
      Osx; therefore, the effects of Osx gene silencing with shRNA lentiviral particles
      on chondrocyte marker gene expression and alkaline phosphatase (ALP) activity
      were investigated. At confluency, gene silencing down-regulated expression of the
      Sox trio (Sox5, 6, 9), Dlx5 and Alp mRNA, as well as ALP enzyme activity. Bone
      morphogenetic protein 2 (BMP2) is known to induce Osx gene expression in
      chondrocytes, and stimulation with BMP2 rescued Osx expression accompanied by up
      regulation of Alp expression and ALP enzyme activity in a dose-dependent manner.
      To clarify the role of Osx in chondrocyte differentiation, cells induced to
      differentiate by 10MUg/ml insulin for 21days were examined. Gene silencing
      inhibited the expression of the hypertrophic chondrocyte marker gene, type X
      collagen (Col X), and attenuated up-regulation of Dlx5 and Alp mRNA, as well as
      ALP enzyme activity. Taken together, these results suggest that Osx is involved
      in chondrogenic gene activation and is a positive regulator of the chondrocyte
      differentiation.

PMID- 21075079
TI  - A role for MGA2, but not SPT23, in activation of transcription of ERG1 in
      Saccharomyces cerevisiae.
AB  - The SaccharomycescerevisiaeMGA2 gene encodes an important regulator of
      unsaturated fatty acid production, by controlling transcription and mRNA
      stability of OLE1, the gene encoding the Delta9 fatty acid desaturase. Lipid
      composition studies indicated that the mga2Delta strain contains elevated
      relative amounts of squalene when compared to wild-type cells. The deletion of
      the MGA2 homologue SPT23 did not impact squalene levels. To explore the role of
      MGA2 in the regulation of sterol synthesis, the transcription of the ERG1 gene,
      which encodes squalene epoxidase, was studied using an ERG1 promoter-lacZ
      reporter gene construct. We report here that in addition to MGA2's role in
      regulation of unsaturated fatty acids, MGA2 is required for full basal expression
      of ERG1. Mga2p was found to be controlled by a novel regulator in its activation
      of ERG1, as neither unsaturated fatty acids nor cobalt affected ERG1 expression,
      as had previously been shown for Mga2p's regulation of OLE1. Further, response to
      miconazole treatment, which inhibits production of ergosterol at a later step in
      the sterol biosynthetic pathway and results in up-regulation of several genes in
      ergosterol synthesis, was not affected in the mga2Delta mutant. In each case, the
      spt23Delta mutant strain shows similar ERG1 expression to wild-type cells, while
      the mga2Delta/spt23Delta strain shows reduced ERG1 expression, comparable to the
      mga2Delta, suggesting that the role of regulation of ERG1 transcription is unique
      to Mga2p.

PMID- 21075080
TI  - The role of blood cell membrane lipids on the mode of action of HIV-1 fusion
      inhibitor sifuvirtide.
AB  - Sifuvirtide is a gp41 based peptide that inhibits HIV-1 fusion with the host
      cells and is currently under clinical trials. Previous studies showed that
      sifuvirtide partitions preferably to saturated phosphatidylcholine lipid
      membranes, instead of fluid-phase lipid vesicles. We extended the study to the
      interaction of the peptide with circulating blood cells, by using the dipole
      potential sensitive probe di-8-ANEPPS. Sifuvirtide decreased the dipole potential
      of erythrocyte and lymphocyte membranes in a concentration dependent manner,
      demonstrating its interaction. Also, the lipid selectivity of the peptide towards
      more rigid phosphatidylcholines was confirmed based on the dipole potential
      variations. Overall, the interaction of the peptide with the cell membranes is a
      contribution of different lipid preferences that presumably directs the peptide
      towards raft-like domains where the receptors are located, facilitating the reach
      of the peptide to its molecular target, the gp41 in its pre-fusion conformation.

PMID- 21075082
TI  - Response property of inferior collicular neurons inherited from peripheral origin
      in mouse.
AB  - The mechanisms underlying spike time coding in auditory system are not well
      understood. Despite of several models proposed to describe the first spike
      latency (FSL), there is no comparison of their respective performance. Here,
      based on FSL data from the central nucleus of inferior colliculus (CIC) in mouse
      to tone stimuli with varying rise function, rise time, and amplitude, we examined
      the previous models by comparing the recorded FSL with derived the FSL,
      respectively. We found that the LIEFTS (leaky integration, event formation,
      temporal summation) threshold model produced better match with the recorded data
      than other models. In addition, the model suggested that the short time constants
      derived from the FSL data (<2 ms) cannot be attributed to IC neurons themselves
      (normally longer than 10 ms), but are similar to those for the inner hair cells
      (around 1.4 ms). Our results suggested that LIEFTS threshold model is a better
      fit for FSL, and FSL properties in central neurons can be inherited along the
      central auditory pathway, likely through faithful relays from the peripheral
      origins.

PMID- 21075081
TI  - Initial evidence linking synaptic superoxide production with poor short-term
      memory in aged mice.
AB  - Unregulated production of reactive oxygen species (ROS) is a marker of cellular
      and organismal aging linked to cognitive decline in humans and rodents. The
      sources of elevated ROS contributing to cognitive decline are unknown. Because
      NADPH oxidase (Nox) inhibition may prevent memory decline with age, we
      hypothesized that Nox and not mitochondrial sources of synaptic ROS production
      are linked to individual variance in cognitive performance in aged mice. Young (8
      months) and aged (26 months) mice were tested in the novel object recognition
      task (NORT). Mitochondrial and Nox ROS production was assayed in isolated
      synaptosomes using spin trapping electron paramagnetic resonance (EPR)
      spectroscopy. Aged mice exhibited variance in NORT performance, with some
      performing similar to young mice while others exhibited poorer short-term memory.
      EPR studies indicated that Nox rather than mitochondria was the major ROS source
      at the synapse, and Nox-induced but not mitochondrial-induced ROS levels
      correlated with NORT performance in aged mice. Our findings support the
      hypothesis that variance in Nox-specific synaptic ROS production may predict
      short-term memory deficits with age.

PMID- 21075083
TI  - Effects of perinatal cocaine exposure on open field behavior and the response to
      corticotropin releasing hormone (CRH) in rat offspring.
AB  - Previous reports indicate that prenatal cocaine exposure alters specific
      behaviors and hypothalamic-pituitary-adrenal axis (HPA) function in the
      offspring. In most previous studies, cocaine was given via subcutaneous
      injections. However intravenous administration more closely mimics human cocaine
      abuse during pregnancy. Therefore, we investigated the effects of prenatal
      cocaine exposure via intravenous injection to the mothers on open field behavior
      and HPA axis function of the offspring. We hypothesized that prenatal cocaine
      exposure decreases immobility in a novel environment, and enhances the HPA
      response to stress. Dams received cocaine (COC) or vehicle (control, CON)
      intravenously from gestation day 8 to postnatal day (PD) 5. Behaviors were
      recorded in the open field on PD 28 (weanlings). As expected, perinatally cocaine
      exposed offspring spent less time immobile and had a longer latency to entering
      the center zone. No other behavioral activities were different between the
      groups. On PD 43-50, adolescent male and female offspring received either
      corticotropin releasing hormone (CRH) or saline intravenously. Plasma
      adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were
      determined before, and up to 60 min after injection. COC-exposed offspring of
      both sexes had higher basal CORT levels. Prenatal cocaine enhanced the CORT
      response to CRH/saline injections up to 60 min in males but not in females. These
      novel results show that perinatal administration of cocaine in a manner that most
      closely mimics human cocaine use has long-term effects on the offspring's
      behavioral response to stress and on HPA axis functions.

PMID- 21075084
TI  - Effect of 3,4-methylenedioxyamphetamine on dendritic spine dynamics in rat
      neocortical neurons--involvement of heat shock protein 27.
AB  - Along with chronic neurotoxic effects, the long-term consumption of amphetamines
      has been associated to psychiatric symptoms and memory disturbances. Dendritic
      spine dynamics have been discussed as a possible morphological correlate.
      However, the underlying mechanisms are still elusive. 3,4
      Methylenedioxyamphetamine (MDA), a major drug of abuse and a main metabolite
      after 3,4-methylenedioxymethamphetamine (MDMA) intake, provokes a loss of
      dendritic spine-like protrusions in primary cultures of rat cortical neurons. 3,4
      Methylenedioxyamphetamine also induced a rapid activation of the p38 mitogen
      activated protein kinase (p38 MAPK) pathway and phosphorylation of heat shock
      protein 27 (hsp27) indicative for its decreased chaperone activity. Concurrent
      pharmacological inhibition of the p38 MAPK by SB203580 abolished hsp27
      phosphorylation and diminished the loss of dendritic spine-like protrusions.
      Moreover, upon MDA treatment dendritic spine-like protrusions were stabilized in
      neurons constitutively expressing hsp27. In parallel experiments we observed a
      robust activation of the heat shock transcription factor 1 (HSF-1) and a
      subsequent increase of hsp27 and hsp70. The regulation of small heat shock
      proteins corroborates the existence of a neuronal stress response after MDA
      treatment. Pharmacological targeting of small heat shock protein phosphorylation
      may provide a new strategy to preserve spine integrity after amphetamine
      exposure.

PMID- 21075085
TI  - Up-regulation of the isoenzymes MAO-A and MAO-B in the human basal ganglia and
      pons in Huntington's disease revealed by quantitative enzyme radioautography.
AB  - Huntington's disease (HD) is a rare genetic disease associated with the
      degeneration of GABAergic striatal projection neurons in the basal ganglia
      leading to movement disorders with behavioral symptoms for which there is
      presently no therapy. Abnormally high levels of monoamine oxidase (MAO) activity,
      which are potentially linked to cytotoxic free radical formation, are known to
      occur during aging and in neurodegenerative disorders (MAO-B is markedly
      increased in plaque-associated astrocytes in Alzheimer's disease). We therefore
      measured, with anatomical resolution, MAO-A and -B activities in 5 cases of HD
      (severity grades 1-3) and age-matched controls by quantitative enzyme
      radioautography using radiolabeled enzyme inhibitors (3)H-Ro 41-1049 and (3)H
      lazabemide, respectively, as high-affinity ligands in vitro. MAO-A was increased
      significantly (ca. 50%; p<0.01) in the putamen and substantia nigra pars compacta
      of the basal ganglia and in the pons. Higher increases in MAO-B (75%-200%;
      p<0.01) occurred in the putamen, ventral striatum, globus pallidus externus and
      internus of the basal ganglia and in the insular cortex. The increased enzyme
      levels (especially of MAO-B) seemed to correlate with the grade of disease
      severity. We conclude that MAO increases in those regions of HD brains which are
      known to undergo neurodegeneration accompanied by glioses. Whether or not this
      increased enzyme activity is a cause or effect of the resulting loss of the
      GABAergic projection neurons in HD is yet to be clarified. Moreover, it remains
      to be seen if selective enzyme inhibitors have therapeutic utility in the
      treatment of HD by reducing oxidative stress locally.

PMID- 21075087
TI  - Potassium-selective microelectrode revealed difference in threshold potassium
      concentration for cortical spreading depression in female and male rat brain.
AB  - It has been found with potassium-selective microelectrodes that the threshold
      extracellular concentration of potassium [K(+)](e) for eliciting fast spreading
      depression from the site of administration 1.5mm away is 80% lower in the rat
      female cortex (8.0 +/- 0.6 mM) than in the male cortex (14.4 +/- 0.4mM). The rate
      of the first slow phase of [K(+)](e) rise before reaching the threshold and speed
      of SD propagation were similar for both sexes as well as the rise of the second
      active fast phase of the [K(+)](e) increase. Lower [K(+)](e) threshold in females
      can facilitate the rapid K(+) release from the nerve tissue cells that may cause
      a cerebrovascular vasodilatation and the attack of migraine pain.

PMID- 21075086
TI  - Endoplasmic reticulum protein BI-1 modulates unfolded protein response signaling
      and protects against stroke and traumatic brain injury.
AB  - Bax-Inhibitor-1 (BI-1) is an evolutionarily conserved cytoprotective protein that
      resides in membranes of the endoplasmic reticulum (ER). BI-1's cytoprotective
      activity is manifested in the context of ER stress, with previous studies showing
      that BI-1 modulates several ER-associated functions, including Unfolded Protein
      Response (UPR) signaling. Here we investigated the role of BI-1 in
      neuroprotection by generating transgenic mice in which BI-1 was constitutively
      expressed from a neuronal-specific promoter. Cultured primary cortical neurons
      from BI-1 transgenic mouse embryos exhibited greater resistance to cell death
      induced by agents known to cause ER stress compared to their non-transgenic
      counterparts. While brain morphology and vasculature of BI-1 mice appeared to be
      unchanged from normal non-transgenic mice, BI-1 transgenic mice showed reduced
      brain lesion volumes and better performance in motoric tests, compared with non
      transgenic littermates, in two models of acute brain injury: stroke caused by
      middle cerebral artery occlusion (MCAO) and traumatic brain injury (TBI) caused
      by controlled cortical impact. Furthermore, brain tissue from BI-1 transgenic
      mice showed reduced levels of apoptotic cells and reduced induction of markers of
      ER stress after brain injury, including CHOP protein expression. In summary, our
      findings demonstrate that enforced neuronal expression of BI-1 reduces ER stress
      and provides protection from acute brain injury, suggesting that strategies for
      enhancing BI-1 expression or activity should be considered for development of new
      therapies for counteracting the consequences of stroke and acute brain trauma.

PMID- 21075088
TI  - P-glycoprotein and breast cancer resistance protein expression and function at
      the blood-brain barrier and blood-cerebrospinal fluid barrier (choroid plexus) in
      streptozotocin-induced diabetes in rats.
AB  - The aim of the study was to investigate the influence of diabetes mellitus type 1
      on expression and function of the ATP-binding cassette transport proteins P
      glycoprotein (Pgp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) at
      the blood-brain barrier and the blood-cerebrospinal fluid barrier formed by the
      choroid plexus. In brain capillary endothelial cells forming the blood-brain
      barrier, Pgp and Bcrp are located in the luminal membrane while apical/sub-apical
      localization was described for Pgp in choroid plexus epithelial cells.
      Alterations in expression or function may lead to damages in barrier integrity
      and may cause brain defects after long term diabetes. Diabetes was induced by
      i.p.-streptozotocin injection 14days prior to performing experiments. RNA and
      protein expression were analyzed in choroid plexus and blood-brain barrier
      capillaries by RT-PCR and Western blot, respectively. Pgp and Bcrp expression was
      increased in blood-brain barrier capillaries; in choroid plexus, only Bcrp showed
      elevated gene expression. Protein expression was not altered. Functional analyses
      were carried out using confocal laser-scanning microscopy in intact isolated
      brain capillaries with the fluorescent Pgp substrate NBD-Cyclosporin A (NBD-CsA)
      and BODIPY(r) FL prazosin as substrate for Bcrp. Consistent with protein
      expression data, no changes in diabetic animals occurred, suggesting an unaltered
      function of Pgp and Bcrp.

PMID- 21075089
TI  - The neural correlates of reasoning about prosocial-helping decisions: an event
      related brain potentials study.
AB  - Providing help to others is a highly valued social practice. This study used
      neurophysiological methods to explore the neural correlates of individuals'
      reasoning about prosocial-helping behaviors and the relation between these
      correlates and self-reports of prosocial personality. Event-related potentials
      (ERP) were recorded while individuals reasoned about others' decisions to provide
      help or not provide help in situations where help was either obviously needed or
      not necessarily needed. Specific examination of the relation between self-reports
      of prosocial personality and the peak amplitude and latency of the P3, an ERP
      component considered to represent the perception and processing of a salient
      response, revealed that individuals' self-ratings of prosocialness were related
      to their ERPs. The findings from this study suggest that there are neural
      correlates for reasoning about prosocial-helping decisions and that there is a
      relation between these neural correlates and individuals' prosocial personality.

PMID- 21075090
TI  - AIF-mediated mitochondrial pathway is critical for the protective effect of
      diazoxide against SH-SY5Y cell apoptosis.
AB  - It has been well established that the mitochondrial ATP-sensitive potassium
      channel (mitoK(ATP)) opener, diazoxide, has protective effects on the heart and
      brain following ischemia/reperfusion injury. However, the mechanism of the
      neuroprotective effects of diazoxide remains unclear. This study highlights the
      anti-apoptotic effects of the drug, which are mediated by specific regulation of
      apoptosis-inducing factor (AIF) in the process of oxygen and glucose deprivation
      (OGD)-induced apoptosis in SH-SY5Y cells. Our data showed that pretreatment with
      diazoxide in SH-SY5Y cells following OGD concentration-dependently increased cell
      viability. Compared to cells induced by OGD alone, cells pretreated with
      diazoxide displayed reduced rates of apoptosis, increased mitochondrial
      transmembrane potential (DeltaPsim), and reduced AIF translocation to the cell
      nucleus. The protective effects of preconditioning with diazoxide were attenuated
      by 5-hydroxydecanoic acid (5-HD), a selective mitoK(ATP) channel antagonist.
      Meanwhile, cell death was blocked in OGD-induced cells stably transfected with
      the AIF-shRNA plasmid, and down-regulation of AIF reduced the diazoxide-mediated
      prevention of cell apoptosis as well as the loss of DeltaPsim induced by OGD.
      Taken together, our results demonstrate for the first time that the AIF-mediated
      mitochondrial pathway plays a critical role in the protective effect of diazoxide
      against SH-SY5Y cell apoptosis induced by OGD. Diazoxide treatment might
      represent a novel therapeutic target for the treatment of ischemic
      cerebrovascular diseases.

PMID- 21075091
TI  - Synergism between methamphetamine and the neuropeptide substance P on the
      production of nitric oxide in the striatum of mice.
AB  - Our laboratory has been investigating the participation of striatal neurokinin-1
      receptors in the methamphetamine (METH)-induced loss of striatal neurons.
      Signaling through these receptors exacerbates the METH-induced striatal
      apoptosis. METH induces the synthesis of nitric oxide (NO) and the latter has
      been linked to the activation of neurodegenerative cascades. In the present
      study, we assessed the role of the neurokinin-1 receptor in the production of
      striatal 3-nitrotyrosine (3-NT) and l-citrulline (indirect indices of NO
      production). To that end, we injected male mice with a bolus of METH (30 mg/kg,
      ip) and visualized striatal neuronal nitric oxide synthase (NOS)-positive cells
      by immunohistochemistry and protein levels by Western blot. The expression of
      neuronal NOS or protein levels at 2, 4 and 8 hours post-METH was unchanged. Next,
      we assessed 3-NT and l-citrulline by immunohistochemistry. At 4 hours post-METH,
      striatal 3-NT and l-citrulline levels were increased 30- and 5-fold,
      respectively, relative to controls and the selective neurokinin-1 receptor
      antagonist WIN-51,708 attenuated these increases. Intrastriatal infusion of the
      neurokinin-1 receptor agonist GR-73632 induced striatal 3-NT production that was
      attenuated with systemic injection of WIN-51,708 or 7-nitroindazole (7-NI, an
      inhibitor of neuronal NOS). Moreover, infusion of calmidazolium (calmodulin
      inhibitor) with GR-73632 prevented the production of 3-NT. These data are
      consistent with the hypothesis that METH-induced production of NO is modulated by
      the striatal neurokinin-1 receptors and that this receptor may participate in the
      biochemical activation of neuronal NOS.

PMID- 21075092
TI  - Expression of Keap1-Nrf2 system and antioxidative proteins in mouse brain after
      transient middle cerebral artery occlusion.
AB  - Reactive oxygen species and their detrimental effects on the brain after
      transient ischemia have been implicated in the pathogenesis of the ischemic
      injury. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid
      2-related factor 2 (Nrf2) system is currently recognized as the major cellular
      defense mechanism under oxidative stress, but the involvement of the Keap1-Nrf2
      system in the ischemic brain injuries has not been fully investigated to date. In
      the present study, we investigated temporal changes of Keap1, Nrf2, and their
      downstream antioxidative proteins in post-ischemic mice brains with respect to
      spacial differences between the peri-infarct regions and the regions destined to
      infarct. In the peri-infarct regions, a steady level of Keap1 showed a
      decremental expression started at 2h of reperfusion after 60 min of transient
      middle cerebral artery occlusion (tMCAO). In contrast, Nrf2 began to show a
      significant increase at 2h with a peak at 8h of reperfusion after tMCAO. Both
      Keap1 and Nrf2 are mainly expressed in neuronal cells but not in glial cells. In
      the same peri-infarct region, downstream antioxidative proteins such as
      thioredoxin, glutathione, and heme oxygenase-1 showed significant increases at
      later time-points of 24-72 h of reperfusion after tMCAO. In the regions destined
      to infarct, a similar trend of expression changes to those in the peri-infarct
      regions was observed in Keap1, Nrf2, and 3 downstream antioxidative proteins with
      much less reactions. The changes found in this study suggest that the induced
      antioxidative stress proteins after cerebral ischemia may play an important
      endogenous neuroprotective response under oxidative stress after ischemic stroke.

PMID- 21075093
TI  - Protective effects of statins on L-DOPA neurotoxicity due to the activation of
      phosphatidylinositol 3-kinase and free radical scavenging in PC12 cell culture.
AB  - Neurotoxic effects have been suggested for l-3,4-dihydroxyphenylalanine (L-DOPA),
      while neuroprotective effects have been proposed for statins. We investigated
      whether certain statins (simvastatin or pitavastatin) could inhibit L-DOPA
      neurotoxicity. Neuronally-differentiated PC12 (nPC12) cells were treated with L
      DOPA and/or statins for 24h, and their viabilities were measured using a cell
      counting kit, trypan blue staining, and 4',6-diamidino-2-phenylindole (DAPI)
      staining. Free radical and specific intracellular signaling protein levels were
      measured with 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western
      blotting, respectively. High concentrations of l-DOPA reduced nPC12 cell
      viability, but combined treatment with statins restored viability. Treatment with
      200 MUM L-DOPA increased free radical and hydroxyl radical levels, but combined
      treatment with 5 MUM statins decreased these levels. Survival-related signaling
      proteins were decreased in nPC12 cells treated with 200 MUM L-DOPA, but combined
      treatment with 5MUM statins significantly increased the levels of these proteins.
      Treatment with 200 MUM L-DOPA significantly increased death-related signaling
      proteins, while combined treatment with 5 MUM statins reduced the levels of these
      proteins. Pretreatment with LY294002, a phosphatidylinositol 3 kinase (PI3K)
      inhibitor, before combined treatment with statins and L-DOPA almost completely
      blocked the protective effects of statins. These results indicate that statins
      reduce L-DOPA neurotoxicity by lowering oxidative stress and by enhancing
      survival signals and inhibiting death signals via activation of the PI3K pathway.

PMID- 21075094
TI  - Anti-tumor effects of B-2, a novel 2,3-disubstituted 8-arylamino-3H-imidazo[4,5
      g]quinazoline derivative, on the human lung adenocarcinoma A549 cell line in
      vitro and in vivo.
AB  - This study evaluated the selective effects of 2-isopropyl-3-butyl-8-(4
      fluorophenylamino)-3H-imidazo[4,5-g]quinazoline (B-2), a member of a series of
      quinazolines, on the cell survival and growth of the non-small cell lung cancer
      (NSCLC) cell line A549 in vitro and in vivo. Cytotoxicity assay, hollow fiber
      assay and cell xenograft model experiment revealed that B-2 showed selective
      effects on A549 cell survival or growth in a dose-dependent manner. At a dose of
      100mg/kg, B-2 showed stronger efficacy on tumor growth inhibition in nude mice
      than Iressa. Exposure of A549 cells to B-2 caused inhibition of EGFR-dependent
      ERK-MAPK activation. In addition, inhibition of cell cycle progression and
      induction of mitochondria-dependent apoptosis might contribute to present the
      multitarget pathway of non-small cell lung cancer treatment of B-2.

PMID- 21075095
TI  - Proteomics of toxic oil syndrome in humans: Phenotype distribution in a
      population of patients.
AB  - OBJECTIVES: Toxic oil syndrome (TOS) is a disease that appeared in Spain in 1981.
      Epidemiological work traced the origin to the ingestion of aniline-adulterated
      rapeseed oil, fraudulently marketed and sold as edible oil. It affected more than
      20,000 people with over 400 deaths in the first 2 years. In 2001 evidence was
      presented that genetic factors could play a role in the susceptibility of
      individuals to the disease. Thus, a prospective study on the differences in gene
      expression in sera between control versus TOS-affected populations, both
      originally exposed to the toxic oil, was undertaken in our laboratory. METHODS:
      Differential protein expression was analyzed by two-dimensional electrophoresis
      (2-DE). Problems related with serum analysis by 2-DE were addressed to improve
      protein detection in the gel images. Three new commercial systems for albumin
      depletion were tested to optimize the detection of minor proteins. The use of
      nonionic reductants or the presence of thiourea in the gels, were also tested.
      RESULTS: From the resulting optimized images, a group of 329 major gel spots was
      located, matched and compared with serum samples. Thirty-five of these protein
      spots were found to be under- or over-expressed in TOS patients (threefold
      increase or decrease). Proteins in these spots were identified by matrix-assisted
      laser desorption/ionization-time of flight (MALDI-TOF) peptide map fingerprinting
      and database search. Several haptoglobin (Hp) isoforms were found to be
      differentially expressed, showing expression phenotypes that could be related
      with TOS. Resolution of the homologous alpha-1s and alpha-1f chains, with a mass
      difference of only 0.043Da, was obtained after guanidation of the protein with O
      methylisourea. We applied this procedure to the study of the distribution of the
      Hp alleles HP(2), HP(1s) and HP(1f) in control versus TOS-affected populations.
      The MALDI-TOF proteotyping method was validated by a parallel analysis of the
      serum samples by 2-DE. CONCLUSIONS: Data obtained from 54 TOS cases and 48
      controls indicate significant differences in the distribution of Hp phenotypes in
      the two populations. Haptoglobin phenotypes have been reported to have biological
      and clinical consequences and have been described as risk factors for several
      diseases. Consequently, it was concluded that haptoglobin polymorphism could play
      a role in TOS.

PMID- 21075097
TI  - On the surface properties of oleate micelles and oleic acid/oleate vesicles
      studied by spin labeling.
AB  - Dilute aqueous systems composed of sodium oleate micelles and sodium oleate/oleic
      acid vesicles were investigated as a function of pH by electron spin resonance
      spectroscopy with TEMPO-stearate TEMPO-stearamide as well as with a positively
      charged water soluble spin label, TEMPO-choline. The dynamics of the three TEMPO
      spin labels were found to be sensitive to changes in the interfacial region of
      the aggregates as a function of pH. The results obtained are consistent with the
      formation of a hydrogen bond network (RCOO(-)<->HOOCR) at the surface of the
      sodium oleate/oleic acid system in the course of the transformation of micelles
      into the closed bilayers (vesicles). Vesicles formation below pH 10 was
      determined independently with a spin labeled glucose derivative.

PMID- 21075096
TI  - Quantitative mass spectrometry reveals the epigenome as a target of arsenic.
AB  - Recent studies reveal that posttranslational modifications on chromatin proteins,
      especially histones, organize genomic DNA and mediate various cellular responses
      to environmental influences. Quantitative mass spectrometric analysis is a
      powerful approach to reveal these dynamic events on chromatin in a systematic
      manner. Here, the effects of arsenic exposure on histone epigenetic state were
      investigated in human UROtsa cells, and a reduction in acetylation level on
      several histone H3 and H4 lysine residues was detected. Furthermore, MYST1 was
      shown to be the major histone acetyltransferase for H4 Lys16 and protect UROtsa
      cells from arsenic toxicity.

PMID- 21075098
TI  - Clinical laboratory indices in the treatment of acromegaly.
AB  - Measurement of serum growth hormone (GH) and insulin-like growth factor-I (IGF-)
      is used to monitor the degree of improvement that occurs following treatment of
      patients with acromegaly. Improvement in GH assay sensitivity has led to changes
      in the definition of normal GH however many studies that assess the predictive
      value of GH were conducted in an era where assays were less sensitive. Other
      problems that have occurred with GH measurements include utilization of different
      standards and failure to prove commutability of commonly accepted standard. GH
      reference ranges vary in their quality and are not stratified for age, sex or
      body mass index. IGF-I measurements are associated with similar problems. They do
      not use a common standard that has been proven to be commutable and results can
      vary widely when the same specimens are assayed in different laboratories.
      Although age and sex stratified reference ranges exist, these do not always have
      adequate numbers of subjects and BMI adjusted ranges are not available. These
      problems have led to significant discordance in a significant number of patients
      wherein the IGF-I and GH values may yield a discrepant prediction of disease
      stabilization. In these cases in general the IGF-I values correlate better with
      the presence of persistent symptoms. Patients who fail to suppress GH to normal
      but have a normal IGF-I have to be monitored carefully for recurrence but usually
      do not require further therapy if they are asymptomatic. For the long term
      assessment of outcome and clinical disease activity measurement of both hormones
      is recommended.

PMID- 21075099
TI  - Assessment of new hyaluronic acid assays and their impact on FibroMeter scores.
AB  - BACKGROUND: We compared three hyaluronic acid (HA) assays and analyzed the impact
      of their variations on FibroMeter scores. METHODS: In a test group of 165
      patients, HA levels were assessed with the commonly used ELISA assay from
      Corgenix, a new ELISA assay from Teco and an immunoturbidimetry assay from Wako,
      this latter tested across three different instruments. Five different FibroMeter
      scores were calculated. RESULTS: Correlation across the three assays (r(s)
      between 0.969 and 0.995) was very good. Means of differences (d) were lower when
      the immunoturbidimetry assay was compared on different instruments: d between 
      3.4 and 2.0 MUg/L. However, a higher value for HA measurement was observed with
      Corgenix assay, compared to the other two assays (Teco and Wako): d between 27.1
      and 36.4 MUg/L. The assessment also demonstrated that HA variations had very
      little impact on FibroMeter scores: 0.0117 for virus and 0.0416 for alcoholic
      fibrosis scores, and between 0.58 and 1.71 for the area of fibrosis (expressed in
      percentage). CONCLUSIONS: The two new assays found lower values of HA, as
      compared to the Corgenix assay. However, these differences had very little impact
      on FibroMeter scores and had no impact on clinical evaluation of liver fibrosis.

PMID- 21075100
TI  - A genetic variant in the gene encoding adrenomedullin predicts the development of
      dysglycemia over 6.4 years in Chinese.
AB  - BACKGROUND: Adrenomedullin, a vasodilatory peptide, facilitates the
      differentiation of pre-adipocytes, and affects lipolysis and glucose uptake. We
      investigated the association of common single nucleotide polymorphisms (SNPs) in
      the gene encoding adrenomedullin (ADM) with dysglycemia in the Hong Kong Chinese
      population. METHODS: Four SNPs were genotyped in 1391 subjects without
      dysglycemia at baseline from the Hong Kong Cardiovascular Risk Factor Prevalence
      Study-2, which had a median follow-up time of 6.4 years. Dysglycemia included
      impaired fasting glucose, impaired glucose tolerance, and diabetes according to
      the WHO 1998 criteria. At follow-up, 382 subjects had developed dysglycemia.
      RESULTS: In stepwise logistic regression, the SNP rs11042725 was a significant
      independent predictor of the development of dysglycemia (OR=1.31, P=0.012),
      together with baseline age (P<0.001), plasma triglycerides (P<0.001), body mass
      index (P=0.004), 2-h glucose after oral glucose tolerance test (P<0.001),
      homeostasis model assessment of insulin resistance index (P=0.045), and follow-up
      duration (P=0.009). The association was more significant in women (P=0.002) and
      in subjects without regular exercise (P=0.001). CONCLUSIONS: Our study suggests a
      potential role of genetic variants in the ADM gene in the development of
      dysglycemia in our local Chinese population.

PMID- 21075101
TI  - Tumor necrosis factor-alpha regulates p27 kip expression and apoptosis in smooth
      muscle cells of human carotid plaques via forkhead transcription factor O1.
AB  - Apoptosis of vascular smooth muscle cells (SMCs) is controlled by a balance
      between the effect of growth factors and cytokines, and is involved in plaque
      instability in advanced atherosclerotic lesions. Recently, we reported high
      levels of atheroma-associated cytokines, including tumor necrosis factor-alpha
      (TNF-alpha), in carotid plaques of symptomatic patients. These cytokines induce
      apoptosis of vascular SMCs, and thus could be responsible for plaque rupture, a
      clinically devastating event. In this study, we examined the effect of TNF-alpha
      on the cell cycle inhibitor p27(kip) and apoptosis of SMCs in human carotid
      plaques, and the underlying mechanism. Both Forkhead box subclass o1 (FoxO1) and
      p27(kip) were more strongly expressed in symptomatic than asymptomatic
      atherosclerotic plaques. TNF-alpha significantly induced the expression of FoxO1
      in asymptomatic plaque SMCs in a dose- and time-dependent manner via JNK
      signaling pathway. TNF-alpha also induced phosphorylation of FoxO1, resulting in
      its cytoplasmic translocation/nuclear exclusion of transcription factors. The
      effect of TNF-alpha was blocked by the PI3K inhibitor, LY294002. Meanwhile, TNF
      alpha not only induced the p27(kip) expression and cell cycle arrest in the G(0)
      G(1) phase, but also enhanced caspase-3 activity and induced apoptosis in SMCs of
      asymptomatic plaques. However, the potential effect of TNF-alpha on the cell
      cycle inhibitor p27(kip) and apoptosis of SMCs was inhibited by siRNA against
      FoxO1 in asymptomatic patients. These data suggest the involvement of FoxO1
      transcription factor in TNF-alpha-induced expression of a cell cycle regulatory
      protein and apoptosis of SMCs, thus regulating the stability of atherosclerotic
      plaques with carotid stenosis.

PMID- 21075102
TI  - Competitive enhancement of HGF-induced epithelial scattering by accessory growth
      factors.
AB  - HGF signaling induces epithelial cells to disassemble cadherin-based adhesion and
      increase cell motility and invasion, a process termed epithelial-mesenchymal
      transition (EMT). EMT plays a major role in cancer metastasis, allowing
      individual cells to detach from the primary tumor, invade local tissue, and
      colonize distant tissues with new tumors. While invasion of vascular and
      lymphatic networks is the predominant route of metastasis, nerves also can act as
      networks for dissemination of cancer cell to distant sites in a process termed
      perineual invasion (PNI). Signaling between nerves and invasive cancer cells
      remains poorly understood, as does cellular decision making that selects the
      specific route of invasion. Here we examine how HGF signaling contributes to PNI
      using reductionist culture model systems. We find that TGFbeta, produced by PC12
      cells, enhances scattering in response to HGF stimulation, increasing both cell
      cell junction disassembly and cell migration. Further, gradients of TGFbeta
      induce migratory mesenchymal cells to undergo chemotaxis towards the source of
      TGFbeta. Interestingly, VEGF suppresses TGFbeta-induced enhancement of
      scattering. These results have broad implications for how combinatorial growth
      factor signaling contributes to cancer metastasis, suggesting that VEGF and
      TGFbeta might modulate HGF signaling to influence route selection during cancer
      progression.

PMID- 21075103
TI  - A model of giant vacuole dynamics in human Schlemm's canal endothelial cells.
AB  - Aqueous humour transport across the inner wall endothelium of Schlemm's canal
      likely involves flow through giant vacuoles and pores, but the mechanics of how
      these structures form and how they influence the regulation of intraocular
      pressure (IOP) are not well understood. In this study, we developed an in vitro
      model of giant vacuole formation in human Schlemm's canal endothelial cells
      (HSCECs) perfused in the basal-to-apical direction (i.e., the direction that flow
      crosses the inner wall in vivo) under controlled pressure drops (2 or 6 mmHg).
      The system was mounted on a confocal microscope for time-lapse en face imaging,
      and cells were stained with calcein, a fluorescent vital dye. At the onset of
      perfusion, elliptical void regions appeared within an otherwise uniformly stained
      cytoplasm, and 3-dimensional reconstructions revealed that these voids were dome
      like outpouchings of the cell to form giant vacuole-like structures or GVLs that
      reproduced the classic "signet ring" appearance of true giant vacuoles.
      Increasing pressure drop from 2 to 6 mmHg increased GVL height (14 +/- 4 vs. 21
      +/- 7 MUm, p < 0.0001) and endothelial hydraulic conductivity (1.15 +/- 0.04 vs.
      2.11 +/- 0.49 MUl min-1 mmHg-1 cm-2; p < 0.001), but there was significant
      variability in the GVL response to pressure between cell lines isolated from
      different donors. During perfusion, GVLs were observed "migrating" and
      agglomerating about the cell layer and often collapsed despite maintaining the
      same pressure drop. GVL formation was also observed in human umbilical vein and
      porcine aortic endothelial cells, suggesting that giant vacuole formation is not
      a unique property of Schlemm's canal cells. However, in these other cell types,
      GVLs were rarely observed "migrating" or contracting during perfusion, suggesting
      that Schlemm's canal endothelial cells may be better adapted to withstand basal
      to-apical directed pressure gradients. In conclusion, we have established an in
      vitro model system to study giant vacuole dynamics, and we have demonstrated that
      this system reproduces key aspects of giant vacuole morphology and behaviour.
      This model offers promising opportunities to investigate the role of endothelial
      cell biomechanics in the regulation of intraocular pressure in normal and
      glaucomatous eyes.

PMID- 21075104
TI  - Seizure-like thalamocortical rhythms initiate in the deep layers of the cortex in
      a co-culture model.
AB  - The oscillatory rhythms underlying many physiological and pathological states,
      including absence seizures, require both the thalamus and cortices for full
      expression. A co-culture preparation combining cortical and thalamic explants
      provides a unique model for investigating how such oscillations initiate and
      spread. Here we investigated the dynamics of synchronized thalamocortical
      activity by simultaneous measurement of field-potential recordings and rapid
      imaging of Ca(2+) transients by fluorescence methods. Spontaneous sustained
      hypersynchronized "seizure-like" oscillations required reciprocal cortico
      thalamocortical connections. Isolated cortical explants can independently develop
      brief discharges, while thalamic explants alone were unable to do so. Rapid
      imaging of Ca(2+) transients demonstrated deep-layer cortical initiation of
      oscillatory network activity in both connected and isolated explants. Further,
      cortical explants derived from a rat model of genetic absence epilepsy showed
      increased bursting duration consistent with an excitable cortex. We propose that
      thalamocortical oscillatory network activity initiates in deep layers of the
      cortex with reciprocal thalamic interconnections enabling sustained hyper
      synchronization.

PMID- 21075105
TI  - Functional MRI of impaired finger dexterity in Parkinson's disease.

PMID- 21075106
TI  - Chronic dizocilpine or apomorphine and development of neuropathy in two animal
      models II: effects on brain cytokines and neurotrophins.
AB  - Dopaminergic and glutamatergic mechanisms are involved in the development and
      modulation of neuropathy. Cytokines and neurotrophins can be also involved in the
      supraspinal maintenance of neuropathic pain. We assessed the effects of chronic
      intraperitoneal (ip) injection of dizocilpine (MK-801), a N-methyl-d-Aspartate
      (NMDA) noncompetitive receptor antagonist, or apomorphine (APO), a dopamine (DA)
      D1 and D2 receptor agonist, on neuropathic manifestations in the chronic
      constriction injury (CCI) and the spared nerve injury (SNI) models of neuropathy
      in rats. Six groups of rats were subjected to SNI or CCI (3 groups each)
      neuropathy and 5-7 days later received daily ip injections of saline, MK-801, or
      APO for two weeks. An additional control group was subjected to sham surgery
      without nerve lesion or injections. Rats were then sacrificed, and levels of IL
      1beta, IL-6, NGF, BDNF and GDNF were determined in the cingulum, striatum, and
      hippocampus. In both models, the neuropathy seen in the saline group was
      associated with decreased BDNF and an increase in IL-1beta, IL-6, NGF and GDNF in
      most brain regions when compared to sham group. Chronic systemic MK-801 or APO
      injections decreased the neuropathic manifestations in both models, increased the
      BDNF level and modulated the other cytokines and neurotrophins. This modulation
      depended on the neuropathy model and the region/side of the brain studied. Our
      results showed that the changes in surpraspinal cytokines and neurotrophins could
      parallel neuropathic manifestations. These changes and the observed hyperalgesia
      can be modulated by chronic systemic injections of NMDA antagonists or DA
      agonists.

PMID- 21075107
TI  - Structural basis for reduced activity of 1-aminocyclopropane-1-carboxylate
      synthase affected by a mutation linked to andromonoecy.
AB  - 1-aminocyclopropane-1-carboxylate synthase (ACS) is a key enzyme in the
      biosynthesis of the plant hormone ethylene. Recently, a new biological role for
      ACS has been found in Cucumis melo where a single point mutation (A57V) of one
      isoform of the enzyme, causing reduced activity, results in andromonoecious
      plants. We present here a straightforward structural basis for the reduced
      activity of the A57V mutant, based on our work on Malus domestica ACS, including
      a new structure of the unliganded apple enzyme at 1.35A resolution.

PMID- 21075109
TI  - Gallstone disease is associated with increased mortality in the United States.
AB  - BACKGROUND & AIMS: Gallstones are common and contribute to morbidity and health
      care costs, but their effects on mortality are unclear. We examined whether
      gallstone disease was associated with overall and cause-specific mortalities in a
      prospective national population-based sample. METHODS: We analyzed data from
      14,228 participants in the third US National Health and Nutrition Examination
      Survey (20-74 years old) who underwent gallbladder ultrasonography from 1988 to
      1994. Gallstone disease was defined as ultrasound-documented gallstones or
      evidence of cholecystectomy. The underlying cause of death was identified from
      death certificates collected through 2006 (mean follow-up, 14.3 years). Mortality
      hazard ratios (HR) were calculated using Cox proportional hazards regression
      analysis to adjust for multiple demographic and cardiovascular disease risk
      factors. RESULTS: The prevalence of gallstones was 7.1% and of cholecystectomy
      was 5.3%. During a follow-up period of 18 years or more, the cumulative mortality
      was 16.5% from all causes (2389 deaths), 6.7% from cardiovascular disease (886
      deaths), and 4.9% from cancer (651 deaths). Participants with gallstone disease
      had higher all-cause mortality in age-adjusted (HR = 1.3; 95% confidence interval
      [CI]: 1.2-1.5) and multivariate-adjusted analysis (HR = 1.3; 95% CI: 1.1-1.5). A
      similar increase was observed for cardiovascular disease mortality (multivariate
      adjusted HR = 1.4; 95% CI: 1.2-1.7), and cancer mortality (multivariate-adjusted
      HR = 1.3; 95% CI: 0.98-1.8). Individuals with gallstones had a similar increase
      in risk of death as those with cholecystectomy (multivariate-adjusted HR = 1.1;
      95% CI: 0.92-1.4). CONCLUSIONS: In the US population, persons with gallstone
      disease have increased mortality overall and mortalities from cardiovascular
      disease and cancer. This relationship was found for both ultrasound-diagnosed
      gallstones and cholecystectomy.

PMID- 21075108
TI  - Probiotics, enteric and diarrheal diseases, and global health.

PMID- 21075110
TI  - The energetic costs of case construction in the caddisfly Limnephilus rhombicus:
      direct impacts on larvae and delayed impacts on adults.
AB  - Caddisflies, whose aquatic larvae build a portable case with silk, are a suitable
      model organism to test the impacts of resource allocation trade-off during
      development and examine the evolution of life-history strategies. In the
      caddisfly Limnephilus rhombicus, adult feeding is minimal. Therefore, the whole
      resources are acquired during the larval phase and must be allocated to case
      construction, growth and reproduction. In this study, the larval energetic
      reserves of L. rhombicus were manipulated by forcing larvae to rebuild their
      cases in the final larval stage. This allowed us to measure the physiological
      cost of construction. First, we recorded oxygen consumption during case
      reconstruction. Second, we measured the sugar, protein and lipid contents of
      larvae forced to rebuild their case and of larvae required only to re-enter on
      their case. Larvae had their sugar, protein and lipid content measured after the
      rebuilding event and 72 h later. The same analyses were carried out with adults
      immediately after emergence. We found that larvae forced to rebuild a case
      consumed 1.5 times more oxygen than control larvae. This energy expenditure
      generated a cost that was estimated to be a loss of larval protein of
      approximately 35%. Insects were unable to compensate for this loss of proteins
      during the end of the larval stage, and their metamorphosis to adults was also
      impacted. Therefore, we suggest that loss of larval protein is linked to silk
      production and may alter fitness.

PMID- 21075111
TI  - Feeding ecology and evidence for amino acid synthesis in the periodical cicada
      (Magicicada).
AB  - The periodical cicadas of the genus Magicicada (including M. septendecim, M.
      cassini, and M. septendecula) have the longest juvenile life span of any insect,
      living underground for 13 or 17 years and feeding exclusively on root xylem
      fluids. Due to their inaccessible life cycles very little is known about cicada
      nutrition, despite the fact that members of Magicicada can achieve a very large
      biomass in woodland habitats east of the Mississippi and hence constitute a major
      part of the ecosystem where they occur in high densities. Live cicadas were
      collected at two sites in early June of 2004, during the emergence of Brood X
      (both M. septendecim and M. cassini were recovered). We used a combination of
      stable isotopic measurements (delta(15)N and delta(13)C) and multivariate
      statistical techniques to test for differences in resource acquisition among the
      cicada species and sexes collected at two locations within the 17-year periodical
      Brood X range. The amino acid constituents of cicada chitin and organs, plus
      xylem extracted from a deciduous sapling, were also analyzed. The data show that
      male and female cicadas have different carbon fractionations, which could reflect
      differential resource utilization due to oviposition in females. Several
      essential amino acids for the cicada were absent in xylem. Carbon-isotopic
      composition of all amino acids in the cicadas was distinctly different from the
      limited set measured in the xylem. Because of the differences in isotopic
      composition, we conclude that amino acids were synthesized de novo rather than
      incorporated directly, most likely produced by endosymbiotic bacteria.

PMID- 21075112
TI  - Heat shock response to hypoxia and its attenuation during recovery in the flesh
      fly, Sarcophaga crassipalpis.
AB  - In this study, pharate adults of the flesh fly Sarcophaga crassipalpis were
      exposed to two, four, seven, or ten days of severe hypoxia (3% oxygen) to
      evaluate its impact on emergence and the expression of genes encoding heat shock
      proteins (Hsps) and heat shock regulatory elements. A four-day exposure to
      hypoxia significantly reduced survival, but more than seven days was required to
      reach the LD(50). Eight genes encoding Hsps, at least one from each major family
      of Hsps (Hsp90, Hsp70, Hsp60, Hsp40, and sHsps) and two genes encoding proteins
      involved in Hsp regulation (heat shock factor, hsf, and sirtuin) were cloned, and
      expression levels were assessed during and after hypoxia using qRT-PCR. Most, but
      not all hsps studied, were significantly up-regulated during hypoxia, and
      expression levels for most of the hsps reverted to control levels a few hours
      after return to normoxia. Hsp70 was the most responsive to hypoxia, increasing
      expression several hundred fold. By contrast, hsp90 and hsp27 showed little
      response to hypoxia but did respond to recovery. Neither hsf nor sirtuin were
      elevated by hypoxia, an observation consistent with their assumed post
      transcriptional regulatory roles. These data demonstrate a strong Hsp response to
      hypoxia, suggesting an important role for Hsps in responding to low oxygen
      environments.

PMID- 21075113
TI  - Monitoring diapause development in the Colorado potato beetle, Leptinotarsa
      decemlineata, under field conditions using molecular biomarkers.
AB  - A multiplex PCR protocol was developed using five diapause-regulated genes to
      monitor diapause development of the Colorado potato beetle under field
      conditions. A total of 870 beetles from the Red River valley of North Dakota and
      Minnesota, USA, were screened for three consecutive years. Out of the 32 possible
      expression profiles, eight could be arranged in chronological order of diapause
      development. These eight profiles account for over 92% of the beetles surveyed.
      Intra-population variation in diapause phenotypes was observed in the field. Some
      beetles were already in the diapause initiation phase in June when the day length
      was greater than 17 h. Inter-seasonal variation in the timing of diapause
      development was also noted. The greatest differences were before the day length
      decreased to less than 15 h. Anomalies in the results, e.g., the presence of the
      diapause maintenance phase profiles in beetles collected on the potato plants,
      argue that laboratory results are not always equivalent with what is observed
      under field conditions.

PMID- 21075114
TI  - Dyssynchrony of Ca2+ release from the sarcoplasmic reticulum as subcellular
      mechanism of cardiac contractile dysfunction.
AB  - Cardiac contractile function depends on coordinated electrical activation
      throughout the heart. Dyssynchronous electrical activation of the ventricles has
      been shown to contribute to contractile dysfunction in heart failure, and
      resynchronization therapy has emerged as a therapeutic concept. At the cellular
      level, coupling of membrane excitation to myofilament contraction is facilitated
      by highly organized intracellular structures which coordinate Ca(2+) release. The
      cytosolic [Ca(2+)] transient triggered by depolarization-induced Ca(2+) influx is
      the result of a gradable and robust high gain process, Ca(2+)-induced Ca(2+)
      release (CICR), which integrates subcellular localized Ca(2+) release events.
      Lack of synchronization of these localized release events can contribute to
      contractile dysfunction in myocardial hypertrophy and heart failure. Different
      underlying mechanisms relate to functional and structural changes in sarcolemmal
      Ca(2+) channels, the sarcoplasmic Ca(2+) release channel or ryanodine receptor,
      RyR, their intracellular arrangement in close proximity in couplons and the loss
      of t-tubules. Dyssynchrony at the subcellular level translates in a reduction of
      the overall gain of CICR at the cellular level and forms an important determinant
      of myocyte contractility in heart failure.

PMID- 21075115
TI  - Molecular architecture and connectivity of the budding yeast Mtw1 kinetochore
      complex.
AB  - Kinetochores are large multiprotein complexes that connect centromeres to spindle
      microtubules in all eukaryotes. Among the biochemically distinct kinetochore
      complexes, the conserved four-protein Mtw1 complex is a central part of the
      kinetochore in all organisms. Here we present the biochemical reconstitution and
      characterization of the budding yeast Mtw1 complex. Direct visualization by
      electron microscopy revealed an elongated bilobed structure with a 25-nm-long
      axis. The complex can be assembled from two stable heterodimers consisting of
      Mtw1p-Nnf1p and Dsn1p-Nsl1p, and it interacts directly with the microtubule
      binding Ndc80 kinetochore complex via the centromere-proximal Spc24/Spc25 head
      domain. In addition, we have reconstituted a partial Ctf19 complex and show that
      it directly associates with the Mtw1 complex in vitro. Ndc80 and Ctf19 complexes
      do not compete for binding to the Mtw1 complex, suggesting that Mtw1 can bridge
      the microtubule-binding components of the kinetochore to the inner centromere.

PMID- 21075116
TI  - Shigella flexneri Spa15 crystal structure verified in solution by double electron
      electron resonance.
AB  - Shigella flexneri Spa15 is a chaperone of the type 3 secretion system, which
      binds a number of effectors to ensure their stabilization prior to secretion. One
      of these effectors is IpgB1, a mimic of the human Ras-like Rho guanosine
      triphosphatase RhoG. In this study, Spa15 alone and in complex with IpgB1 has
      been studied by double electron electron resonance, an experiment that gives
      distance information showing the spacial separation of attached spin labels. This
      distance is explained by determining the crystal structure of the spin-labeled
      Spa15 where labels are seen to be buried in hydrophobic pockets. The double
      electron electron resonance experiment on the Spa15 complex with IpgB1 shows that
      IpgB1 does not bind Spa15 in the same way as is seen in the homologous Salmonella
      sp. chaperone:effector complex InvB:SipA.

PMID- 21075117
TI  - Arginine kinase: joint crystallographic and NMR RDC analyses link substrate
      associated motions to intrinsic flexibility.
AB  - The phosphagen kinase family, including creatine and arginine kinases (AKs),
      catalyzes the reversible transfer of a "high-energy" phosphate between ATP and a
      phosphoguanidino substrate. They have become a model for the study of both
      substrate-induced conformational change and intrinsic protein dynamics. Prior
      crystallographic studies indicated large substrate-induced domain rotations, but
      differences among a recent set of AK structures were interpreted as a plastic
      deformation. Here, the structure of Limulus substrate-free AK is refined against
      high-resolution crystallographic data and compared quantitatively with NMR
      chemical shifts and residual dipolar couplings (RDCs). This demonstrates the
      feasibility of this type of RDC analysis of proteins that are large by NMR
      standards (42 kDa) and illuminates the solution structure, free from crystal
      packing constraints. Detailed comparison of the 1.7 A resolution substrate-free
      crystal structure against the 1.7 A transition-state analog complex shows large
      substrate-induced domain motions that can be broken down into movements of
      smaller quasi-rigid bodies. The solution-state structure of substrate-free AK is
      most consistent with an equilibrium of substrate-free and substrate-bound
      structures, with the substrate-free form dominating, but with varying
      displacements of the quasi-rigid groups. Rigid-group rotations evident from the
      crystal structures are about axes previously associated with intrinsic
      millisecond dynamics using NMR relaxation dispersion. Thus, "substrate-induced"
      motions are along modes that are intrinsically flexible in the substrate-free
      enzyme and likely involve some degree of conformational selection.

PMID- 21075118
TI  - Biochemical and structural characterization of beta-catenin interactions with
      nonphosphorylated and CK2-phosphorylated Lef-1.
AB  - In the Wnt/beta-catenin signaling pathway, beta-catenin activates target genes
      through its interactions with the T-cell factor/lymphoid enhancer-binding factor
      (TCF/Lef) family of transcription factors. The crystal structures of complexes
      between the beta-catenin armadillo domain and the Lef-1 N-terminal domain show
      that the overall conformation and many of the interactions are similar to other
      published structures of TCFs bound to beta-catenin. However, a second salt bridge
      in other TCF-beta-catenin structures is absent in the structure of beta-catenin
      Lef-1 complex, indicating that this feature is not obligatory for beta-catenin
      binding. Casein kinase II (CK2) has been shown to act as a positive regulator of
      Wnt signaling, and Lef-1 is a substrate of CK2. In vitro phosphorylation of
      purified Lef-1 was used to examine the effect of CK2 on the interaction of Lef-1
      with beta-catenin. Mass spectrometry data show that CK2 phosphorylation of Lef-1
      N-terminal domain results in a single phosphorylation site at Ser40. Isothermal
      titration calorimetry revealed that beta-catenin binds to nonphosphorylated or
      CK2-phosphorylated Lef-1 with the same affinity, which is consistent with the
      absence of phospho-Ser40 interactions in the crystal structure of phosphorylated
      Lef-1 N-terminal domain bound to beta-catenin. These data indicate that the
      effect of CK2 on the Wnt/beta-catenin pathway does not appear to be at the level
      of the Lef-1-beta-catenin interaction.

PMID- 21075120
TI  - Understanding soaring bird migration through interactions and decisions at the
      individual level.
AB  - Many soaring bird species migrate southwards in autumn from their breeding
      grounds in Europe and Central Asia towards their wintering grounds. Our knowledge
      about interactions between migrating birds, thermal selection during migration
      and mechanisms that lead to flocking or convergent travel networks is still very
      limited. To start investigating these aspects we developed an individual-based
      simulation model that describes the local interactions between birds and their
      environment during their migratory flight, leading to emergent patterns at larger
      scales. The aim of our model is to identify likely decision rules with respect to
      thermal selection and navigation. After explaining the model, it is applied to
      analyse the migration of white storks (Ciconia ciconia) over part of its
      migration domain. A model base-run is accompanied by a sensitivity analysis. It
      appears that social interactions lead to the use of fewer thermals and slight
      increases in distance travelled. Possibilities for different model extensions and
      further model application are discussed.

PMID- 21075119
TI  - Tuning riboswitch regulation through conformational selection.
AB  - The S(MK) box riboswitch, which represents one of three known classes of S
      adenosylmethionine (SAM)-responsive riboswitches, regulates gene expression in
      bacteria at the level of translation initiation. In contrast to most
      riboswitches, which contain separate domains responsible for ligand recognition
      and gene regulation, the ligand-binding and regulatory domains of the S(MK) box
      riboswitch are coincident. This property was exploited to allow the first atomic
      level characterization of a functionally intact riboswitch in both the ligand
      bound state and the ligand-free state. NMR spectroscopy revealed distinct
      mutually exclusive RNA conformations that are differentially populated in the
      presence or in the absence of the effector metabolite. Isothermal titration
      calorimetry and in vivo reporter assay results revealed the thermodynamic and
      functional consequences of this conformational equilibrium. We present a
      comprehensive model of the structural, thermodynamic, and functional properties
      of this compact RNA regulatory element.

PMID- 21075121
TI  - Pathway knockout and redundancy in metabolic networks.
AB  - The robustness and stability of complex cellular networks is often attributed to
      the redundancy of components, including genes, enzymes and pathways. Estimation
      of redundancy is still an open question in systems biology. Current theoretical
      tools to measure redundancy have various strengths and shortcomings in providing
      a comprehensive description of metabolic networks. Specially, there is a lack of
      effective measures to cover different perturbation situations. Here we present a
      pathway knockout algorithm to improve quantitative measure of redundancy in
      metabolic networks grounded on the elementary flux mode (EFM) analysis. The
      proposed redundancy measure is based on the average ratio of remaining EFMs after
      knockout of one EFM in the unperturbed state. We demonstrated with four example
      systems that our algorithm overcomes limits of previous measures, and provides
      additional information about redundancy in the situation of targeted attacks.
      Additionally, we compare existing enzyme knockout and our pathway knockout
      algorithm by the mean-field analysis, which provides mathematical expression for
      the average ratio of remaining EFMs after both types of knockout. Our results
      prove that multiple-enzymes knockout does not always yield more information than
      single-enzyme knockout for evaluating redundancy. Indeed, pathway knockout
      considers additional effects of structural asymmetry. In the metabolic networks
      of amino acid anabolism in Escherichia coli and human hepatocytes, and the
      central metabolism in human erythrocytes, we validate our mean-field solutions
      and prove the capacity of pathway knockout algorithm. Moreover, in the E. coli
      model the two sub-networks synthesizing amino acids that are essential and those
      that are non-essential for humans are studied separately. In contrast to previous
      studies, we find that redundancy of two sub-networks is similar with each other,
      and even sub-networks synthesizing essential amino acids can be more redundant.

PMID- 21075122
TI  - Modeling resistance to genetic control of insects.
AB  - The sterile insect technique is an area-wide pest control method that reduces
      pest populations by releasing mass-reared sterile insects which compete for mates
      with wild insects. Modern molecular tools have created possibilities for
      improving and extending the sterile insect technique. As with any new insect
      control method, questions arise about potential resistance. Genetic RIDL((r))(1)
      (Release of Insects carrying a Dominant Lethal) technology is a proposed
      modification of the technique, releasing insects that are homozygous for a
      repressible dominant lethal genetic construct rather than being sterilized by
      irradiation. Hypothetical resistance to the lethal mechanism is a potential
      threat to RIDL strategies' effectiveness. Using population genetic and population
      dynamic models, we assess the circumstances under which monogenic biochemically
      based resistance could have a significant impact on the effectiveness of releases
      for population control. We assume that released insects would be homozygous
      susceptible to the lethal genetic construct and therefore releases would have a
      built-in element of resistance dilution. We find that this effect could prevent
      or limit the spread of resistance to RIDL constructs; the outcomes are subject to
      competing selective forces deriving from the fitness properties of resistance and
      the release ratio. Resistance that is spreading and capable of having a
      significant detrimental impact on population reduction is identifiable, signaling
      in advance a need for mitigating action.

PMID- 21075123
TI  - Internal dynamics of actin structures involved in the cell motility and adhesion:
      Modeling of the podosomes at the molecular level.
AB  - Podosomes are involved in the spreading and motility of various cells to a solid
      substrate. These dynamical structures, which have been proven to consist of a
      dense actin core surrounded by an actin cloud, nucleate when the cell comes in
      the vicinity of a substrate. During the cell spreading or motion, the podosomes
      exhibit collective dynamical behaviors, forming clusters and rings. We design a
      simple model aiming at the description of internal molecular turnover in a single
      podosome: actin filaments form a brush which grows from the cellular membrane
      whereas their size is regulated by the action of a severing agent, the gelsolin.
      In this framework, the characteristic sizes of the core and of the cloud, as well
      as the associated characteristic times are expressed in terms of basic
      ingredients. Moreover, the collocation of the actin and gelsolin in the podosome
      is understood as a natural result of the internal dynamics.

PMID- 21075124
TI  - In vivo optical imaging of revascularization after brain trauma in mice.
AB  - Revascularization following brain trauma is crucial to the repair process. We
      used optical micro-angiography (OMAG) to study endogenous revascularization in
      living mice following brain injury. OMAG is a volumetric optical imaging method
      capable of in vivo mapping of localized blood perfusion within the scanned tissue
      beds down to capillary level imaging resolution. We demonstrated that OMAG can
      differentiate revascularization progression between traumatized mice with and
      without soluble epoxide hydrolase (sEH) gene deletion. The time course of
      revascularization was determined from serial imaging of the traumatic region in
      the same mice over a one-month period of rehabilitation. Restoration of blood
      volume at the lesion site was more pronounced in sEH knockout mice than in wild
      type mice as determined by OMAG. These OMAG measurements were confirmed by
      histology and showed that the sEH knockout effect may be involved in enhancing
      revascularization. The correlation of OMAG with histology also suggests that OMAG
      is a useful imaging tool for real-time in vivo monitoring of post-traumatic
      revascularization and for evaluating agents that inhibit or promote endogenous
      revascularization during the recovery process in small rodents.

PMID- 21075125
TI  - Enhanced susceptibility to the GABA antagonist pentylenetetrazole during the
      latent period following a pilocarpine-induced status epilepticus in rats.
AB  - A variety of acute brain insults bear the risk of subsequent development of
      chronic epilepsy. Enhanced understanding of the brain alterations underlying this
      process may ultimately lead to interventions that prevent, interrupt or reverse
      epileptogenesis in people at risk. Various interventions have been evaluated in
      rat models of symptomatic epilepsy, in which epileptogenesis was induced by
      status epilepticus (SE) or traumatic brain injury (TBI). Paradoxically, recent
      data indicated that administration of proconvulsant drugs after TBI or SE exerts
      antiepileptogenic or disease-modifying effects, although epilepsy is often
      considered to represent a decrease in seizure threshold. Surprisingly, to our
      knowledge, it is not known whether alterations in seizure threshold occur during
      the latent period following SE. This prompted us to study seizure threshold
      during and after the latent period following SE induced by lithium/pilocarpine in
      rats. Timed intravenous infusion of the GABA(A) receptor antagonist
      pentylenetetrazole (PTZ) was used for this purpose. The duration of the latent
      period was determined by continuous video/EEG monitoring. Compared to control
      seizure threshold determined before SE, threshold significantly decreased two
      days after SE, but returned to pre-SE control thereafter. Moreover, the duration
      of PTZ-induced seizures was significantly increased throughout the latent period,
      which ranged from 6 to 10 days after SE. This increased susceptibility to PTZ
      likely reflects the complex alterations in GABA-mediated transmission that occur
      during the latent period following SE. The data will allow developing dosing
      regimens for evaluation of whether treatment with subconvulsant doses of PTZ
      during the latent period affects the development of epilepsy.

PMID- 21075126
TI  - Low concentrations of methamidophos do not alter AChE activity but modulate
      neurotransmitters uptake in hippocampus and striatum in vitro.
AB  - AIMS: Methamidophos (Meth) is a toxic organophosphorus compound (OP) that
      inhibits acetylcholinesterase enzyme (AChE) and induces neurotoxicity. As the
      mechanism of its neurotoxic effects is not well understood, the aim of the
      present study was to evaluate the effects of Meth on glutamate and gamma
      aminobutyric acid (GABA) uptake and correlate with cell viability and AChE and
      Na(+)/K(+)-ATPase enzyme activities in striatum and hippocampus slices exposed to
      low concentrations (0.05 to 1.0 MUM) of Meth. MAIN METHODS: Hippocampal and
      striatal slices of rat brain were exposed to Meth for 5 min ([(3)H]Glutamate
      uptake) or 15 min ([(3)H]GABA uptake) for assays. The enzyme activities and cell
      viability were also accessed at both times in hippocampal and striatal slices and
      homogenates. KEY FINDINGS: At concentrations that did not inhibit AChE, Meth
      caused changes in glutamate uptake in striatal (0.05 and 1.0 MUM Meth) and
      hippocampal (1.0 MUM Meth) slices. GABA uptake was increased by the pesticide in
      striatum at 0.5 and 1.0 MUM and in hippocampus at 0.05 MUM. After 3.5h of Meth
      exposure, striatal and hippocampal cells showed no changes in viability as well
      as no inhibition of Na(+)/K(+)-ATPase were observed after 5 or 15 min exposure to
      Meth in the same brain structures. SIGNIFICANCE: Results suggest that Meth, even
      without changing the AChE activity can modify somehow the neurotransmitters
      uptake. However, further studies are necessary to clarify if this modulation in
      glutamate or GABA uptake may be responsible to cause some disturbance in behavior
      or in other neurochemical parameters following low Meth exposure in vivo.

PMID- 21075127
TI  - Interference in simultaneously perceiving and producing facial expressions-
      evidence from electromyography.
AB  - The goal of the current studies was to examine perception-action interactions in
      a socially relevant domain. Social interactions are based on a mutual
      understanding of the emotions and actions of others. We assume that the
      perception of emotional actions also stimulates a parallel action preparation in
      the perceiver, underlining the common coding theory. We report two experiments
      aimed to examine whether the perception of socially relevant facial actions
      (e.g., happy vs. angry facial expressions) interact with the execution of such
      actions. More specifically, we use a stimulus-response compatibility paradigm, in
      which subjects responded to the gender of a face by either smiling or frowning
      while ignoring the fact that the presented face is also randomly either smiling
      or frowning. We measured reaction time (RT) as onset latency on the two large
      muscle groups used for smiling (zygomaticus major) and frowning (corrugator
      supercilii) using electromyography. Experiment 1 showed that on compatible
      trials, in which perceived facial expression and actually produced facial
      expression matched, RTs were shorter than on incompatible trials. Experiment 2
      used pre-instructed (i.e., blocked) responses and replicated the compatibility
      effect, suggesting that the effect is functionally located not in response
      selection but in response initiation or execution. We discuss these results in
      relation to cognitive mechanisms of common coding of perception and action and to
      the human mirror neuron system.

PMID- 21075128
TI  - Specific impairment of visual spatial covert attention mechanisms in Parkinson's
      disease.
AB  - Visual deficits in early and high level processing nodes have been documented in
      Parkinson's disease (PD). Non-motor high level visual integration deficits in PD
      seem to have a cortical basis independently of a low level retinal contribution.
      It is however an open question whether sensory and visual attention deficits can
      be separated in PD. Here, we have explicitly separated visual and attentional
      disease related patterns of performance, by using bias free staircase procedures
      measuring psychophysical contrast sensitivity across visual space under covert
      attention conditions with distinct types of cues (valid, neutral and invalid).
      This further enabled the analysis of patterns of dorsal-ventral (up-down) and
      physiological inter-hemispheric asymmetries. We have found that under these
      carefully controlled covert attention conditions PD subjects show impaired
      psychophysical performance enhancement by valid attentional cues. Interestingly,
      PD patients also show paradoxically increased visual homogeneity of spatial
      performance profiles, suggesting flattening of high level modulation of spatial
      attention. Finally we have found impaired higher level attentional modulation of
      contrast sensitivity in the visual periphery, where mechanisms of covert
      attention are at higher demands. These findings demonstrate a specific loss of
      attentional mechanisms in PD and a pathological redistribution of spatial
      mechanisms of covert attention.

PMID- 21075129
TI  - Functional roles and cultural modulations of the medial prefrontal and parietal
      activity associated with causal attribution.
AB  - Causal understanding of physical events is culturally universal. However,
      behavioral studies suggest that how we perceive causality is culturally
      sensitive, with East Asian culture emphasizing contextual factors and Western
      culture emphasizing dispositional factors guiding causal relationships. The
      present study investigated potential neural substrates of the cultural difference
      in causal attribution of physical events. Using functional magnetic resonance
      imaging, Experiment 1 scanned Chinese subjects during causality or motion
      direction judgments when viewing animations of object collisions and identified a
      causal-attribution related neural circuit consisting of the medial/lateral
      prefrontal cortex, left parietal/temporal cortex, and cerebellum. Moreover, by
      manipulating the task demand of causal inference and the complexity of contextual
      information in physical events, we showed that the medial prefrontal activity was
      modulated by the demand to infer causes of physical events whereas the left
      parietal activity was modulated by contextual complexity of physical events.
      Experiment 2 investigated cultural differences in the medial prefrontal and left
      parietal activity associated with causal attribution of physical events by
      scanning two independent groups of American and Chinese subjects. We found that,
      while the medial prefrontal activity involved in causality judgments was
      comparable in the two cultural groups, the left parietal activity associated with
      causality judgments was stronger in Chinese than in Americans regardless of
      whether the contextual information was attended. Our findings suggest that causal
      inference in the medial prefrontal cortex is universally implicated in causal
      reasoning whereas contextual processing in the left parietal cortex is sensitive
      to cultural differences in causality perception.

PMID- 21075130
TI  - WITHDRAWN: Development of a sensitive liquid phase-radioimmunoassay of 7alpha
      methyl-19-nortestosterone.
AB  - This article has been withdrawn at the request of the Publisher and the Editor-in
      Chiefs. The Publisher apologizes for any inconvenience this may cause. The full
      Elsevier Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21075132
TI  - Use of external metabolizing systems when testing for endocrine disruption in the
      T-screen assay.
AB  - Although, it is well-established that information on the metabolism of a
      substance is important in the evaluation of its toxic potential, there is limited
      experience with incorporating metabolic aspects into in vitro tests for endocrine
      disrupters. The aim of the current study was a) to study different in vitro
      systems for biotransformation of ten known endocrine disrupting chemicals (EDs):
      five azole fungicides, three parabens and 2 phthalates, b) to determine possible
      changes in the ability of the EDs to bind and activate the thyroid receptor (TR)
      in the in vitro T-screen assay after biotransformation and c) to investigate the
      endogenous metabolic capacity of the GH3 cells, the cell line used in the T
      screen assay, which is a proliferation assay used for the in vitro detection of
      agonistic and antagonistic properties of compounds at the level of the TR. The
      two in vitro metabolizing systems tested the human liver S9 mix and the PCB
      induced rat microsomes gave an almost complete metabolic transformation of the
      tested parabens and phthalates. No marked difference the effects in the T-screen
      assay was observed between the parent compounds and the effects of the tested
      metabolic extracts. The GH3 cells themselves significantly metabolized the two
      tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall
      the results and qualitative data from the current study show that an in vitro
      metabolizing system using liver S9 or microsomes could be a convenient method for
      the incorporation of metabolic and toxicokinetic aspects into in vitro testing
      for endocrine disrupting effects.

PMID- 21075131
TI  - Computational estimation of rainbow trout estrogen receptor binding affinities
      for environmental estrogens.
AB  - Environmental estrogens have been the subject of intense research due to their
      documented detrimental effects on the health of fish and wildlife and their
      potential to negatively impact humans. A complete understanding of how these
      compounds affect health is complicated because environmental estrogens are a
      structurally heterogeneous group of compounds. In this work, computational
      molecular dynamics simulations were utilized to predict the binding affinity of
      different compounds using rainbow trout (Oncorhynchus mykiss) estrogen receptors
      (ERs) as a model. Specifically, this study presents a comparison of the binding
      affinity of the natural ligand estradiol-17beta to the four rainbow trout ER
      isoforms with that of three known environmental estrogens 17alpha
      ethinylestradiol, bisphenol A, and raloxifene. Two additional compounds, atrazine
      and testosterone, that are known to be very weak or non-binders to ERs were
      tested. The binding affinity of these compounds to the human ERalpha subtype is
      also included for comparison. The results of this study suggest that, when
      compared to estradiol-17beta, bisphenol A binds less strongly to all four
      receptors, 17alpha-ethinylestradiol binds more strongly, and raloxifene has a
      high affinity for the alpha subtype only. The results also show that atrazine and
      testosterone are weak or non-binders to the ERs. All of the results are in
      excellent qualitative agreement with the known in vivo estrogenicity of these
      compounds in the rainbow trout and other fishes. Computational estimation of
      binding affinities could be a valuable tool for predicting the impact of
      environmental estrogens in fish and other animals.

PMID- 21075133
TI  - In vitro evaluation of the immunotoxic potential of perfluorinated compounds
      (PFCs).
AB  - There is evidence from both epidemiology and laboratory studies that
      perfluorinated compounds may be immunotoxic, affecting both cell-mediated and
      humoral immunity. The overall goal of this study was to investigate the
      mechanisms underlying the immunotoxic effects of perfluorooctane sulfonate (PFOS)
      and perfluorooctane acid (PFOA), using in vitro assays. The release of the pro
      inflammatory cytokines IL-6, IL-8, and TNF-alpha was evaluated in
      lipolysaccharide (LPS)-stimulated human peripheral blood leukocytes and in the
      human promyelocytic cell line THP-1, while the release of IL-4, IL-10 and IFN
      gamma was evaluated in phytohaemagglutinin (PHA)-stimulated peripheral blood
      leukocytes. PFOA and PFOS suppressed LPS-induced TNF-alpha production in primary
      human cultures and THP-1 cells, while IL-8 was suppressed only in THP-1 cells. IL
      6 release was decreased only by PFOS. Both PFOA and PFOS decreased T-cell
      derived, PHA-induced IL-4 and IL-10 release, while IFN-gamma release was affected
      only by PFOS. In all instances, PFOS was more potent than PFOA. Mechanistic
      investigations carried out in THP-1 cells demonstrated that the effect on
      cytokine release was pre-transcriptional, as assessed by a reduction in LPS
      induced TNF-alpha mRNA expression. Using siRNA, a role for PPAR-alpha could be
      demonstrated for PFOA-induced immunotoxicity, while an inhibitory effect on LPS
      induced I-kappaB degradation could explain the immunomodulatory effect of PFOS.
      The dissimilar role of PPAR-alpha in PFOA and PFOS-induced immunotoxicity was
      consistent with the differing effects observed on LPS-induced MMP-9 release:
      PFOA, as the PPAR-alpha agonist fenofibrate, modulated the release, while PFOS
      had no effect. Overall, these studies suggest that PFCs directly suppress
      cytokine secretion by immune cells, and that PFOA and PFOS have different
      mechanisms of action.

PMID- 21075134
TI  - Sphingosine kinase localization in the control of sphingolipid metabolism.
AB  - The sphingosine kinases (sphingosine kinase-1 and -2) have been implicated in a
      variety of physiological functions. Discerning their mechanism of action is
      complicated because in addition to producing the potent lipid second messenger
      sphingosine-1-phosphate, sphingosine kinases, both by producing sphingosine-1
      phosphate and consuming sphingosine, have profound effects on sphingolipid
      metabolism. Sphingosine kinase-1 translocates to the plasma membrane upon agonist
      stimulation and this translocation is essential for the pro-oncogenic properties
      of this enzyme. Many of the enzymes of sphingolipid metabolism, including the
      enzymes that degrade sphingosine-1-phosphate, are membrane bound with restricted
      subcellular distributions. In the work described here we explore how subcellular
      localization of sphingosine kinase-1 affects the downstream metabolism of
      sphingosine-1-phosphate and the access of sphingosine kinase to its substrates.
      We find, surprisingly, that restricting sphingosine kinase to either the plasma
      membrane or the endoplasmic reticulum has a negligible effect on the rate of
      degradation of the sphingosine-1-phosphate that is produced. This suggests that
      sphingosine-1-phosphate is rapidly transported between membranes. However we also
      find that cytosolic or endoplasmic-reticulum targeted sphingosine kinase
      expressed at elevated levels produces extremely high levels of dihydrosphingosine
      1-phosphate. Dihydrosphingosine is a proximal precursor in ceramide biosynthesis.
      Our data indicate that sphingosine kinase can divert substrate from the ceramide
      de novo synthesis pathway. However plasma membrane-restricted sphingosine kinase
      cannot access the pool of dihydrosphingosine. Therefore whereas sphingosine
      kinase localization does not affect downstream metabolism of sphingosine-1
      phosphate, localization has an important effect on the pools of substrate to
      which this key signaling enzyme has access.

PMID- 21075135
TI  - Activation of an innate immune response in large numbers of permeabilized
      Drosophila embryos.
AB  - Innate immunity in Drosophila involves the inducible expression and synthesis of
      antimicrobial peptides. We have previously shown that not only Drosophila larvae
      and adults, but also embryos, are capable of mounting an immune response after
      injection of bacterial substances. To simplify genetic dissection of the
      signaling pathways involved in immune-gene regulation we developed a procedure
      for permeabilization of large number of embryos and subsequent infiltration with
      bacterial fragments. This approach, which promoted expression of CecropinA1- and
      Diptericin-driven beta-gal expression in the epidermis of more than 90% of the
      treated embryos, will enable analysis of mutants that are embryonic lethal. Thus,
      genes that are involved in essential pleiotrophic functions, in addition to being
      candidates in immune-regulation will be amenable for analysis of their
      involvement in the fly's immune defense.

PMID- 21075136
TI  - Molecular identification and expression analysis of a novel tumor necrosis factor
      receptor from the black rockfish, Sebastes schlegelii.
AB  - Members of the tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies
      play crucial roles in both innate and adaptive immunity. In the present study, we
      isolated the full-length cDNA for black rockfish (Sebastes schlegelii) TNFR
      (BrTNFR). This cDNA is 2405 bp in length and contains a 939-bp open reading
      frame, a 27-bp 5' untranslated region, and a 1439-bp 3' untranslated region
      including a polyadenylation signal (AATAAA) and polyadenylation site. The 313
      amino-acid predicted BrTNFR sequence is homologous to other TNFR sequences,
      contains four cysteine-rich domains and a death-effector domain (DED), and lacks
      a transmembrane region. Expression of BrTNFR mRNA was detected in eight different
      tissues from healthy black rockfish and was highest in peripheral blood
      lymphocytes and gills. In analyses of mitogen-stimulated BrTNFR expression in
      peripheral blood lymphocytes, expression of BrTNFR mRNA was observed between 1
      and 24h after stimulation with lipopolysaccharide, concanavalin A/phorbol
      myristate acetate, or poly I:C. Although the data suggest that BrTNFR represents
      an ancestral member of the TNFR superfamily, the orthology of TNFR in teleost
      fish is difficult to establish because few TNFRs have been identified in these
      species.

PMID- 21075137
TI  - Phylogenetic and developmental study of CD4, CD8 alpha and beta T cell co
      receptor homologs in two amphibian species, Xenopus tropicalis and Xenopus
      laevis.
AB  - CD4 and CD8 co-receptors play critical roles in T cell development and activation
      by interacting both with T cell receptors and MHC molecules. Although homologs of
      these genes have been identified in many jawed vertebrates, there are still
      unresolved gaps concerning their evolution and specialization in MHC interaction
      and T cell function. Using experimental and computational procedures we
      identified CD4, CD8alpha and CD8beta gene homologs both in Xenopus tropicalis,
      whose full genome has been sequenced, and its sister species Xenopus laevis.
      Multiple alignments of deduced amino acid sequences reveal a poor conservation of
      the residues involved in binding of CD4 to MHC class II, and CD8alpha to class I
      in non-mammalian species, presumably related to the co-evolutionary pressure of
      MHC I and II genes. Phylogenetic study suggests that Xenopodinae co-receptor
      genes are more closely related to their homologs in other tetrapods than those of
      bony fish. Furthermore, the developmental and cell-specific expression patterns
      of these genes in X. laevis are very similar to that of mammals. X. laevis CD4 is
      mainly expressed by peripheral non-CD8 T cells and detected in the thymus as
      early as four days post-fertilization (dpf) at the onset of thymic organogenesis.
      CD8beta expression is specific to adult surface CD8(+) T cells and thymocytes,
      and is first detected in the thymus at 5 dpf in parallel with productive TCRgamma
      transrcipts, whereas productive TCRbeta and alpha rearrangements are not detected
      before 7-9 dpf.

PMID- 21075138
TI  - Proteomic analysis of zebrafish (Danio rerio) infected with infectious spleen and
      kidney necrosis virus.
AB  - Iridovirus infections remain a severe problem in aquaculture industries
      worldwide. Infectious spleen and kidney necrosis virus (ISKNV), the type species
      of the genus Megalocytovirus in the family Iridoviridae, has caused significant
      economic losses among freshwater fish in different Asian countries. To
      investigate the molecular mechanism of iridoviral pathogenesis, we analyzed the
      differential proteome from the spleen of ISKNV-infected zebrafish through two
      dimensional gel electrophoresis (2-DE). Mass spectrometry revealed 35 altered
      cellular protein spots, including 15 upregulated proteins and 20 downregulated
      proteins at five days post-infection. The altered host proteins were classified
      into 13 categories based on their biological processes: cytoskeletal protein,
      stress response, lipoprotein metabolism, ubiquitin-proteasome pathway,
      carbohydrate metabolism, signal transduction, proteolysis, ion binding,
      transport, metabolic process, catabolic process, biosynthesis, and oxidation
      reduction. Moreover, 14 corresponding genes of the differentially expressed
      proteins were validated by RT-PCR. Western blot analysis further demonstrated the
      changes in alpha-tubulin, beta-actin, HSC70, and major capsid protein (MCP)
      during infection. beta-Actin was selected for further study via co
      immunoprecipitation analyses, which confirmed that the cellular beta-actin
      interacts with the MCP protein of ISKNV in the infected zebrafish. These findings
      provide insight into the interactions between iridoviruses (especially ISKNV) and
      host, as well as the mechanism and pathogenesis of ISKNV infections.

PMID- 21075139
TI  - Infection with the wMel and wMelPop strains of Wolbachia leads to higher levels
      of melanization in the hemolymph of Drosophila melanogaster, Drosophila simulans
      and Aedes aegypti.
AB  - Introduction of the life-shortening strain of Wolbachia pipientis, wMelPop, into
      the key dengue vector, Aedes aegypti, and the anti-pathogen effects in Wolbachia
      infected hosts highlights the need for more research into its interactions with
      its original host, Drosophila melanogaster, and the novel mosquito host. The
      visual difference in darkness between the eggs of wMelPop Wolbachia-infected and
      uninfected mosquito hosts after egg deposition led to further investigation into
      melanization levels of the insects. Both D. melanogaster and A. aegypti infected
      with wMelPop showed increased levels of melanization, especially in females. This
      result was also seen in D. melanogaster and Drosophila simulans infected with the
      closely related wMel strain. D. simulans infected with other strains of Wolbachia
      did not display this difference. HPLC analysis of hemolymph from mosquitoes
      showed that this difference was not due to dopamine levels in the host as they
      were no different in wMelPop-infected and control mosquitoes before or after
      blood feeding.

PMID- 21075140
TI  - Age and sex differences in the effects of the immunosuppressants cyclosporine,
      sirolimus and everolimus on rat brain metabolism.
AB  - Application of the widely used immunosuppressant (ISS) cyclosporine (CsA) is
      severely limited by a number of serious side-effects such as kidney and
      neurotoxicity. As we have shown before, CsA exhibits metabolic toxicity in brain
      models. The macrolide ISSs sirolimus (SRL) and everolimus (RAD) are capable of
      modulating these CsA-induced effects. It was our aim to study the age-dependent
      metabolic changes in the rat brain after ISS-treatment and the possible role of
      the blood-brain-barrier in modulation of CsA metabolic toxicity. Young and adult
      rats were treated orally with one ISS alone or in combination with CsA for six
      days. Metabolic changes were assessed by nuclear magnetic resonance (NMR)
      spectroscopy of brain extracts as toxicodynamic endpoints. Brain P-glycoprotein
      (P-gp) and ISS concentrations were determined as pharmacokinetic endpoints. Young
      rats were more susceptible to CsA-induced inhibition of the Krebs cycle
      (glutamate: 78% of controls, glutamine: 82%, GABA: 71% in young vs. 85%, 89%, 92%
      in adult rats). Increased glycolysis after CsA-treatment was sufficient to
      maintain the energy state at control levels in adult brains, but not in the young
      rat brains (phosphocreatine: 35%). Tissue concentrations of CsA and SRL within
      the brain of young rats were three-fold higher, while concentrations of P-gp were
      three-fold higher in adult rat brains. Our results suggest that age-dependent
      differences in the blood-brain barrier led to increased ISS brain concentrations
      and hence inhibition of brain energy metabolism.

PMID- 21075141
TI  - A new DTL-electrode holder for recording of electroretinograms in animals.
AB  - PURPOSE: Contact lens electrodes (CLEs) are frequently used to register
      electroretinograms (ERGs) in small animals such as mice or rats. CLEs are
      expensive to buy or difficult to be produced individually. In addition, CLE's
      have been noticed to elicit inconstant results and they carry potential to injure
      the cornea. Therefore, a new electrode holder was constructed based on the
      clinically used DTL-electrode and compared to CLEs. MATERIAL AND METHODS: ERGs
      were recorded with both electrode types in nine healthy Brown-Norway rats under
      scotopic conditions. For low intensity responses a Naka-Rushton function was
      fitted and the parameters V(max), k and n were analyzed. The a-wave, b-wave and
      oscillatory potentials were analyzed for brighter flash intensities (1-60 scot
      cds/m2). Repeatability was assessed for both electrode types in consecutive
      measurements. RESULTS: The new electrode holder was faster in setting up than the
      CLE and showed lower standard deviations. No corneal alterations were observed.
      Slightly higher amplitudes were recorded in most of the measurements with the new
      electrode holder (except amplitudes induced by 60 cds/m2). A Bland-Altman test
      showed good agreement between the DTL holder and the CLE (mean difference 35.2
      MUV (Holder-CLE)). Pearson's correlation coefficient for test-retest-reliability
      was r=0.783. CONCLUSIONS: The DTL holder was superior in handling and caused far
      less corneal problems than the CLE and produced comparable or better
      electrophysiological results. The minimal production costs and the possibility of
      adapting the DTL holder to bigger eyes, such as for dogs or rabbits, offers with
      broader application prospects.

PMID- 21075142
TI  - The membrane chamber: a new type of in vitro recording chamber.
AB  - In vitro brain slice electrophysiology is a powerful and highly successful
      technique where a thin slice is cut from the brain and kept alive artificially in
      a recording chamber. The design of this recording chamber is pivotal to the
      success and the quality of such experiments. Most often one of two types of
      chambers is used today, the interface chamber or the submerged chamber. These
      chambers, however, have the disadvantage that they are limited in either their
      experimental or their physiological properties respectively. Here we present a
      new working principle for an in vitro chamber design which aims at combining the
      advantages of the classical designs whilst overcoming their disadvantages. This
      is achieved by using a semipermeable membrane on which the slice is placed. The
      membrane allows for a fast flow of artificial cerebrospinal fluid of up to at
      least 17 ml/min. Due to a Bernoulli effect, this high speed flow also causes a
      64% increase in flow of solution across the membrane on which the slice rests.
      The fact that the membrane is transparent introduces the possibility of wide
      field inverted optical imaging to brain slice electrophysiology. The utility of
      this setup was demonstrated in the recording of local field potential, single
      cell and voltage sensitive dye imaging data simultaneously from an area smaller
      then 1/8mm(2). The combination of all these features in the membrane chamber make
      it a versatile and promising device for many current and future in vitro
      applications, especially in the regard to optical imaging.

PMID- 21075144
TI  - Anti-hepatitis C virus activity of Acacia confusa extract via suppressing
      cyclooxygenase-2.
AB  - Chronic hepatitis C virus (HCV) infection continues to be an important cause of
      morbidity and mortality by chronic hepatitis, cirrhosis and hepatocellular
      carcinoma (HCC) throughout the world. It is of tremendous importance to discover
      more effective and safer agents to improve the clinical treatment on HCV
      carriers. Here we report that the n-butanol-methanol extract obtained from Acacia
      confusa plant, referred as ACSB-M4, exhibited the inhibition of HCV RNA
      replication in the HCV replicon assay system, with an EC(50) value and
      CC(50)/EC(50) selective index (SI) of 5 +/- 0.3 MUg/ml and >100, respectively.
      Besides, ACSB-M4 showed antiviral synergy in combination with IFN-alpha and as
      HCV protease inhibitor (Telaprevir; VX-950) and polymerase inhibitor (2'-C
      methylcytidine; NM-107) by a multiple linear logistic model and isobologram
      analysis. A complementary approach involving the overexpression of COX-2 protein
      in ACSB-M4-treated HCV replicon cells was used to evaluate the antiviral action
      at the molecular level. ACSB-M4 significantly suppressed COX-2 expression in HCV
      replicon cells. Viral replication was gradually restored if COX-2 was added
      simultaneously with ACSB-M4, suggesting that the anti-HCV activity of ACSB-M4 was
      associated with down-regulation of COX-2, which was correlated with the
      suppression of nuclear factor-kappaB (NF-kappaB) activation. ACSB-M4 may serve as
      a potential protective agent for use in the management of patients with chronic
      HCV infection.

PMID- 21075143
TI  - Measuring antiviral activity of benzimidazole molecules that alter IRES RNA
      structure with an infectious hepatitis C virus chimera expressing Renilla
      luciferase.
AB  - Major progress has been made in developing infectious HCV cell culture systems
      and these systems have been useful in identifying novel HCV antivirals. However,
      more rapid and sensitive assays using infectious cell based HCV systems would
      facilitate the development of additional antivirals, including small molecules
      directed at unique targets such as the HCV RNA internal ribosomal entry site
      (IRES). We have found that the V3 region (28 aa) of NS5A of HCV JFH1 can be
      deleted from the genome with only modest effects on the titer of infectious virus
      produced in cell culture. Moreover, the V3 region can be replaced with the
      Renilla reniformis luciferase (Rluc) gene resulting in an infectious virus that
      stably expresses an NS5A-Rluc fusion protein. Infected cells cultured in 96-well
      plates provided a robust luciferase signal that accurately reflected the
      production of infectious virus. This infectious HCV reporter system was used to
      test the activity of three benzimidazole compounds that bind the HCV RNA IRES.
      Compounds in this chemical class of small molecules bind and alter the IRES RNA
      structure at low to sub-micromolar concentrations and interfere with viral
      replication. The current study shows that these compounds inhibit HCV replication
      in an infectious HCV cell culture system, defines their IC(50) in this system,
      and provides a platform for the rapid testing of next generation inhibitors.

PMID- 21075145
TI  - Modeling Parkinson's disease genetics: altered function of the dopamine system in
      Adh4 knockout mice.
AB  - Class IV alcohol dehydrogenase (ADH4) efficiently reduces aldehydes produced
      during lipid peroxidation, and may thus serve to protect from toxic effects of
      aldehydes e.g. on neurons. We hypothesized that ADH4 dysfunction may increase
      risk for Parkinson's disease (PD) and previously reported association of an ADH4
      allele with PD. We found that a promoter polymorphism in this allele induced a 25
      30% reduction of transcriptional activity. Based on these findings, we have now
      investigated whether Adh4 homo- (Adh4-/-) or heterozygous (Adh4+/-) knockout mice
      display any dopamine system-related changes in behavior, biochemical parameters
      or olfaction compared to wild-type mice. The spontaneous locomotor activity was
      found to be similar in the three groups, whereas administration of d-amphetamine
      or apomorphine induced a significant increase in horizontal activity in the Adh4
      /- mice compared to wild-type mice. We measured levels of monoamines and their
      metabolites in striatum, frontal cortex and substantia nigra and found increased
      levels of dopamine and DOPAC in substantia nigra of Adh4-/- mice. Investigation
      of olfactory function revealed a reduced sense of smell in Adh4-/- mice
      accompanied by alterations in dopamine metabolite levels in the olfactory bulb.
      Taken together, our results suggest that lack of Adh4 gene activity induces
      changes in the function of the dopamine system, findings which are compatible
      with a role of loss-of-function mutations in ADH4 as possible risk factors for
      PD.

PMID- 21075146
TI  - Functional lateralization of the baso-lateral amygdala neural circuits modulating
      the motivated exploratory behaviour in rats: role of histamine.
AB  - Functional laterality appears to be present in many brain functions in man and
      animals. The existence of paired neural circuits which act differentially to
      modulate a specific behavioural function seems to be an evolutionary successful
      strategy in animal evolution. In spite of many examples described in mammals,
      birds and other vertebrates and invertebrates, still its intrinsic mechanism is
      not completely understood. In this work the participation of the baso-lateral
      amygdala (BLA) on lateralized motivated exploratory behaviour and the possible
      influence of histamine neurons in these mechanisms were studied in rats.
      Different groups of animals under xylacine-ketamine anesthesia were implanted
      with microinjection guide cannulae into the right or left BLA. 72 h after
      implantation, animals were tested in hole-board cage (OVM) with a novelty object
      positioned in the center of the arena, as a model of exploration of a non
      conflictive environment, and 24h later they were tested in the Elevated
      Asymmetric Plus Maze (APM) as a model of conflictive exploration. In the day of
      the experiment, lidocaine was applied into the left, or right BLA in order to
      block the electrical activity of BLA neurons. Saline in the contralateral BLA was
      considered control. Results showed that exploratory activity in the OVM was
      significantly inhibited when lidocaine was microinjected into the left BLA, and
      no changes were observed when lidocaine was applied into the right BLA. When
      histamine was microinjected into the right BLA and lidocaine into the
      contralateral BLA, head-dipping, rearing, and focalized exploration behaviour
      were significantly inhibited. In the APM, lidocaine treatment increased equally
      the exploration of the "single wall" and "high and low walls" arms of the
      labyrinth, independently if blocking of electrical activity of the BLA neurons
      was performed in the left or right amygdala. Histamine treatment inhibited
      significantly exploration of the lesser fear-inducing arms of the labyrinth but
      its effect was more pronounced when histamine microinjection was in the left BLA.
      In conclusion, present evidence support the lateralized participation of the
      amygdala on exploratory behaviour and histamine neurons appear to mediate part of
      these differential modulations.

PMID- 21075148
TI  - Evidence for prenylation-dependent targeting of a Ykt6 SNARE in Plasmodium
      falciparum.
AB  - Ykt6 proteins are the most versatile fusogens in eukaryotic cells, and the only
      SNAREs that can be both prenylated and acylated at a C-terminal CAAX motif.
      Unlike yeast and mammalian cells where a single Ykt6 gene is expressed, the
      Plasmodium falciparum genome encodes two Ykt6 proteins. We have investigated the
      expression and prenylation of the Ykt6 orthologue, PfYkt6.1 in intra-erythrocytic
      stages of P. falciparum. PfYkt6.1 localized to the parasite Golgi and other
      unidentified cytoplasmic compartments, and was partly cytosolic (~50% in early
      trophozoites). The membrane-association of PfYkt6.1 was dependent on the presence
      of a conserved C-terminal CAAX motif (CCSIM). By expressing full-length and
      mutant proteins in Escherichia coli, we have shown that PfYkt6.1 indeed serves as
      substrate for prenylation by P. falciparum farnesyltransferases. Surprisingly,
      PfYkt6.1 could also be geranylgeranylated by parasite extracts independent of the
      C-terminal amino acid residue. Deletion of the CAAX motif inhibited both
      farnesylation and geranylgeranylation activities. Additionally, the PfYkt6.1
      heptapeptide KQCCSIM, corresponding to the C-terminal CAAX sequence, inhibited
      the parasite farnesyltransferase activity with an IC(50) of 1 MUM. Our findings
      underscore the importance of CAAX motif-derived peptidomimetics for antimalarial
      drug development.

PMID- 21075149
TI  - The activity and hydrogen peroxide sensitivity of the peroxiredoxins from the
      parasitic nematode Haemonchus contortus.
AB  - The requirement of aerobic organisms to control damage caused by reactive oxygen
      species has led to the evolution of the antioxidant systems. Peroxiredoxins are a
      large family of peroxidases which detoxify hydrogen peroxide at the expense of
      thiols. The parasitic nematode Haemonchus contortus contains two peroxiredoxins,
      HcPrx1 a mitochondrial protein and HcPrx2 a cytoplasmic protein. Although both
      peroxiredoxins contain the conserved eukaryotic motifs 'GGLG' and 'YF',
      identified as critical for hydrogen peroxide instability, both were stable to
      high concentrations of hydrogen peroxide, demonstrating different functions to
      their mammalian counterparts. H. contortus also contains two thioredoxin
      reductases and five different thioredoxin-like proteins. The activity of both
      peroxiredoxins was specific for the thioredoxin system; however, both could also
      be regenerated by the glutathione system when coupled to the nematode specific
      thioredoxin HcTrx5. Analysis of homologous genes in Caenorhabditis elegans showed
      that only CePrx2, which is secreted, was sensitive to the external oxidant
      hydrogen peroxide. However, both peroxiredoxins KO C. elegans were sensitive to
      intracellular free radicals and both peroxiredoxins protected DNA from free
      radical attack. The results demonstrate that the hydrogen peroxide detoxification
      and the antioxidant activity of the peroxiredoxins are separate activities that
      are independent of the 'GGLG' and 'YF' motifs.

PMID- 21075147
TI  - An atypical proprotein convertase in Giardia lamblia differentiation.
AB  - Proteolytic activity is important in the lifecycles of parasites and their
      interactions with hosts. Cysteine proteases have been best studied in Giardia,
      but other protease classes have been implicated in growth and/or differentiation.
      In this study, we employed bioinformatics to reveal the complete set of putative
      proteases in the Giardia genome. We identified 73 peptidase homologs distributed
      over 5 catalytic classes in the genome. Serial analysis of gene expression of the
      G. lamblia lifecycle found thirteen protease genes with significant
      transcriptional variation over the lifecycle, with only one serine protease
      transcript upregulated late in encystation. The translated gene sequence of this
      encystation-specific transcript was most similar to eukaryotic subtilisin-like
      proprotein convertases (SPC), although the typical catalytic triad was not
      identified. Epitope-tagged gSPC protein expressed in Giardia under its own
      promoter was upregulated during encystation with highest expression in cysts and
      it localized to encystation-specific secretory vesicles (ESV). Total gSPC from
      encysting cells produced proteolysis in gelatin gels that co-migrated with the
      epitope-tagged protease in immunoblots. Immuno-purified gSPC also had gelatinase
      activity. To test whether endogenous gSPC activity is involved in
      differentiation, trophozoites and cysts were exposed to the specific serine
      proteinase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride
      (AEBSF). After 21 h encystation, a significant decrease in ESV was observed with
      1mM AEBSF and by 42 h the number of cysts was significantly reduced, but
      trophozoite growth was not inhibited. Concurrently, levels of cyst wall proteins
      1 and 2, and AU1-tagged gSPC protein itself were decreased. Excystation of G.
      muris cysts was also significantly reduced in the presence of AEBSF. These
      results support the idea that serine protease activity is essential for Giardia
      encystation and excystation.

PMID- 21075151
TI  - Novel reduction-sensitive micelles for triggered intracellular drug release.
AB  - Novel reduction-sensitive micelles based on poly(ethylene oxide)-b-poly(N
      methacryloyl-N'-(t-butyloxycarbonyl)cystamine) (PEO-b-PMABC) diblock copolymers
      were developed and applied for triggered intracellular drug release. PEO-b-PMABC
      block copolymers were synthesized by reversible addition-fragmentation chain
      transfer (RAFT) polymerization of MABC with dithioester-capped PEO as macroRAFT
      agent. Gel permeation chromatography (GPC) and (1)H NMR analysis showed that the
      copolymers have controlled compositions and molecular weights, indicating the
      living nature of polymerization. These copolymers were self-assembled into
      micelles. The physicochemical characteristics and reduction-sensitivity of the
      resultant micelles were investigated by fluorescence measurement, transmission
      electron microscopy (TEM), and dynamic light scattering (DLS). The results showed
      that PEO-b-PMABC micelles are stable at normal physiologic condition but readily
      cleaved into free copolymers under reducing environment. In vitro release of
      doxorubicin (DOX) and cell experiments showed that the drug-loaded PEO-b-PMABC
      micelles accomplished much faster drug release under reducing condition and
      higher anticancer efficacy as compared to the control without reduction
      sensitivity, indicating great potential of PEO-b-PMABC micelles for efficient
      intracellular drug delivery.

PMID- 21075150
TI  - Calcium signaling in osteoclasts.
AB  - It has long been known that many bone diseases, including osteoporosis, involve
      abnormalities in osteoclastic bone resorption. As a result, there has been
      intense study of the mechanisms that regulate both the differentiation and bone
      resorbing function of osteoclast cells. Calcium (Ca(2+)) signaling appears to
      play a critical role in the differentiation and functions of osteoclasts.
      Cytoplasmic Ca(2+) oscillations occur during RANKL-mediated osteoclastogenesis.
      Ca(2+) oscillations provide a digital Ca(2+) signal that induces osteoclasts to
      up-regulate and autoamplify nuclear factor of activated T cells c1 (NFATc1), a
      Ca(2+)/calcineurin-dependent master regulator of osteoclastogenesis. Here we
      review previous studies on Ca(2+) signaling in osteoclasts as well as recent
      breakthroughs in understanding the basis of RANKL-induced Ca(2+) oscillations,
      and we discuss possible molecular players in this specialized Ca(2+) response
      that appears pivotal for normal bone function. This article is part of a Special
      Issue entitled: 11th European Symposium on Calcium.

PMID- 21075153
TI  - Energy compensation in enterally fed children.
AB  - Limited exposure to solid food in early childhood may affect the development of
      appetite regulation. We used formal satiation studies to assess energy
      compensation in children who have been artificially fed. Subjects were 11
      children, median age 4.5 years (range 1-10) who were formerly (n=4) or currently
      (n=5) mainly tube fed or supplement fed (n=2), with a range of surgical or
      neurodevelopmental problems. On 2 separate days a high-energy preload (HEP) and
      low-energy preload (LEP) drink were given followed by a multi-item test lunch. A
      compensation index (COMPX) score was derived as follows: COMPX (%)=[(Meal(lep)
      Meal(hep))/(Preload(hep)-Preload(lep))]* 100. The median (range) COMPX of the
      participants was 70% (-73% to 178%). The 8 boys tended to compensate more (median
      99%) than the 3 girls (30%; P Mann-Whitney=0.1), but there was no clear
      association of compensation with age. Although a small preliminary study, this
      suggests that children who have been artificially fed demonstrate energy
      compensation comparable to that of normally fed children.

PMID- 21075152
TI  - Tumor-targeted delivery of liposome-encapsulated doxorubicin by use of a peptide
      that selectively binds to irradiated tumors.
AB  - Tumor-targeted drug delivery improves anti-tumor efficacy and reduces systemic
      toxicity by limiting bioavailability of cytotoxic drugs to within tumors.
      Targeting reagents, such as peptides or antibodies recognizing molecular targets
      over-expressed within tumors, have been used to improve liposome-encapsulated
      drug accumulation within tumors and resulted in enhanced tumor growth control. In
      this report, we expand the scope of targeting reagents by showing that one
      peptide, HVGGSSV which was isolated from an in vivo screening of phage-displayed
      peptide library due to its selective binding within irradiated tumors, enabled
      highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and
      resulted in enhanced cytotoxicity within tumors. Targeting liposomes (TL) and non
      targeting liposomes (nTL) were labeled with Alexa Fluor 750. Biodistribution of
      the liposomes within tumor-bearing mice was studied with near infrared (NIR)
      imaging. In the single dose pharmacokinetic study, the liposomal doxorubicin has
      an extended circulation half life as compared to the free doxorubicin. Targeting
      liposomes partitioned to the irradiated tumors and improved drug deposition and
      retention within tumors. The tumor-targeted delivery of doxorubicin improved
      tumor growth control as indicated with reduced tumor growth rate and tumor cell
      proliferation, enhanced tumor blood vessel destruction, and increased treatment
      associated apoptosis and necrosis of tumor cells. Collectively, the results
      demonstrated the remarkable capability of the HVGGSSV peptide in radiation-guided
      drug delivery to tumors.

PMID- 21075154
TI  - Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L
      deprenyl using whole hemisphere autoradiography.
AB  - In the human brain the monoaminooxidase-B enzyme or MAO-B is highly abundant in
      astrocytes. As astrocyte activity and, consequently, the activity of the MAO-B
      enzyme, is up-regulated in neuroinflammatory processes, radiolabelled analogues
      of deprenyl may serve as an imaging biomarker in neuroinflammation and
      neurodegeneration, including Alzheimer's disease. In the present study [(11)C]-L
      deprenyl, the PET radioligand version of L-deprenyl or selegiline(r), a selective
      irreversible MAO-B inhibitor was used in whole hemisphere autoradiographic
      experiments in human brain sections in order to test the radioligand's binding to
      the MAO-B enzyme in human brain tissue, with an eye on exploring the
      radioligand's applicability as a molecular imaging biomarker in human PET
      studies, with special regard to diagnostic detection of reactive astrogliosis.
      Whole hemisphere brain sections obtained from Alzheimer patients and from age
      matched control subjects were examined. In control brains the binding of [(11)C]
      L-deprenyl was the highest in the hippocampus, in the basal ganglia, the
      thalamus, the substantia nigra, the corpus geniculatum laterale, the nucleus
      accumbens and the periventricular grey matter. In Alzheimer brains significantly
      higher binding was observed in the temporal lobes and the white matter.
      Furthermore, in the Alzheimer brains in the hippocampus, temporal lobe and white
      matter the binding negatively correlated with Braak stages. The highest binding
      was observed in Braak I-II, whereas it decreased with increasing Braak grades.
      The increased regional binding in Alzheimer brains coincided with the presence of
      an increased number of activated astrocytes, as demonstrated by correlative
      immunohistochemical studies with GFAP in adjacent brain slices. Deprenyl itself
      as well as the MAO-B antagonist rasagiline did effectively block the binding of
      the radioligand, whereas the MAO-A antagonist pirlindole did not affect it.
      Compounds with high affinity for the PBR system did not block the radioligand
      binding either, providing evidence for the specificity of [(11)C]-L-deprenyl for
      the MAO-B enzyme. In conclusion, the present observations indicate that [(11)C]-L
      deprenyl may be a promising and selective imaging biomarker of increased MAO-B
      activity in the human brain and can therefore serve as a prospective PET tracer
      targeting neuroinflammation and neurodegeneration.

PMID- 21075155
TI  - Hypobaric hypoxia modulates brain biogenic amines and disturbs sleep
      architecture.
AB  - Sojourners to high altitude experience poor-quality of sleep due to hypobaric
      hypoxia (HH). Brain neurotransmitters are the key regulators of sleep
      wakefulness. Scientific literature has limited information on the role of brain
      neurotransmitters involved in sleep disturbance in HH. The present study aimed to
      investigate the time dependent changes in neurotransmitter levels and enzymes
      involved in the biosynthesis of brain neurotransmitters in frontal cortex, brain
      stem, cerebellum, pons and medulla and the effect of these alterations on sleep
      architecture in HH. Thirty adult Sprague-Dawley rats, body weight of 230-250 g
      were exposed to simulated altitude ~7620 m, 282 mm Hg, partial pressure of O(2)
      59 mm Hg for 7 and 14 days continuously in an animal decompression chamber. After
      7 and 14 days of HH, brain nor-epinephrine and dopamine levels were significantly
      increased in frontal cortex, brain stem, cerebellum and pons and medulla whereas
      serotonin level was significantly reduced in frontal cortex and pons and medulla
      after 14 days of HH. Tyrosine hydroxylase level in locus coeruleus (LC) was
      significantly increased whereas Choline Acetyl Transferase and Glutamic Acid
      Decarboxylase (GAD) levels were significantly reduced in laterodorsal-tegmentum
      and pedunculopontine-tegmentum after 7 days of HH. GAD was also reduced in LC
      after 7 days HH. Alteration in these neurotransmitters and enzyme levels was
      accompanied with reduction in quality and quantity of sleep. There was a
      significant increase in sleep latency, rapid eye movement (REM) latency, duration
      of active awake, quiet awake, quiet sleep and a significant decrease in duration
      of REM sleep and deep sleep on day 7 and 14 of HH. It was concluded that HH
      alters the expression of enzymes linked to sleep neurotransmitter synthesis
      pathway and subsequent loss of homeostasis at neurotransmitter level disrupts the
      sleep pattern in hypobaric hypoxia.

PMID- 21075156
TI  - High frequency of low-risk human leukocyte antigen class II genotypes in latent
      celiac disease.
AB  - Human leukocyte antigen (HLA) class II genotypes in latent celiac disease, a
      clinical variant of celiac disease (CD) have been scarcely studied. The aim of
      this work was to investigate whether latent CD and CD share similar frequencies
      of HLA class II genotypes. HLA class II genotypes of CD patients compared with
      controls were subdivided in the following at-risk groups: DQB1*02/DQB1*02 (43.0%,
      odds ratio [OR] 8.02, p < 0.0001), DQB1*0302/DQB1*02 (12.2%, OR 2.77, p =
      0.0002), DQB1*02/DQB1*X (39.2%, OR 1.23, p = 0.1903), DQB1*0302/DQB1*X (3.4%, OR
      0.35, p = 0.0064) and DQB1*X/DQB1*X (0.8%, OR 0.01, p = 0.0001) where X is
      neither DQB1*0302 nor DQB1*02. Next, HLA class II genotypes of 21 latent CD
      patients were compared with the above at-risk groups. Only one latent CD patient
      (4.8%) was found in the high risk DQB1*02/DQB1*02 group, three (14.3%) were
      DQB1*0302/DQB1*02, one (4.8%) was DQB1*0302/DQB1*X and the remaining 16 (76.2%)
      showed the DQB1*02/DQB1*X genotype. Noteworthy, the only 1 patient with the
      DQB1*02/DQB1*02 high risk genotype did not carry the DR3-DQB1*02/DR3-DQB1*02 or
      the DR3-DQB1*02/DR7-DQB1*02 but the uncommon DR3-DQB1*02/DR4-DQB1*02 genotype.
      These data suggest that latent CD is prevalently associated with low-risk HLA
      class II genotypes.

PMID- 21075158
TI  - Pituitary volume in patients with panic disorder.
AB  - Panic patients have many functional deficiencies in the hypothalamic-pituitary
      adrenal (HPA) axis. Previous studies have shown changed pituitary gland volume in
      some psychiatric disorders that have functional deficiencies in the HPA axis.
      However, to date no study has evaluated the pituitary gland volume in patients
      with panic disorder (PD). We investigated the pituitary gland volume in patients
      with PD (n=27) and age- and sex-matched healthy controls (n=27), using 1.5-T
      magnetic resonance imaging in this study. Analysis showed that patients with PD
      had significantly smaller pituitary volume compared to healthy subjects. Patients
      with agoraphobia especially had a significantly smaller pituitary volume than
      patients without agoraphobia. There was a significant relationship between the
      pituitary volume and both the severity of symptoms and the illness duration in
      the patient group. The results show that patients with PD have reduced pituitary
      volume, which may reflect the functional abnormalities seen in this disorder.
      These findings may help us better understand the pathology of PD.

PMID- 21075157
TI  - Prevalence and qualitative properties of circulating anti-human leukocyte antigen
      alloantibodies after pregnancy: no association with unexplained recurrent
      miscarriage.
AB  - In pregnant women, circulating alloantibodies, triggered by exposure to paternal
      HLA antigens, are frequently detectable. The finding of lower alloantibody levels
      in women who experience spontaneous abortion (miscarriage) has led to the
      speculation that antipaternal antibodies could favor maintenance of pregnancy,
      whereas their lack poses a risk of miscarriage. Postulating a role of
      alloantibodies in the pathogenesis of unexplained abortion, we examined whether
      different categories of recurrent miscarriage (RM) can be distinguished according
      to prevalence or distinct qualitative properties of anti-human leukocyte antigen
      (HLA) antibody patterns. Sera obtained from 167 women with RM were assessed for
      complement- and non-complement-fixing anti-HLA alloreactivity using Luminex-based
      bead array technology. Women with RM had less often detectable anti-HLA class I
      and/or II reactivity (19%) compared with a control group of 96 multiparous women
      without a history of miscarriage (49%). However, analysis of different categories
      of RM (unknown [n = 112] versus known cause [n = 55]; primary [n = 125] versus
      secondary RM [n = 42]) did not reveal any differences regarding antibody
      prevalence, number of targeted HLA single antigens, antigen specificity, binding
      density, or complement-fixing ability of detected alloantibodies. Our results do
      not support a link between anti-HLA antibody formation and RM, and argue against
      a diagnostic value of alloantibody detection in the diagnostic work-up of women
      with RM.

PMID- 21075159
TI  - Antioxidant and antitumor activities of Artemisia campestris and Thymelaea
      hirsuta from southern Tunisia.
AB  - The essential oil of Artemisia campestris and the ethanol-water, hexane and water
      extracts of A. campestris and Thymelaea hirsuta collected in southern of Tunisia
      were investigated for their antioxidant (DPPH, ABTS and beta-carotene methods)
      and antitumor growth inhibition of human colon cancer HT-29 cells using MTT test
      activities. All the A. campestris extracts tested at high concentrations (100
      MUg/ml) showed activity ranging from 19.5% for essential oil to 64.4% of negative
      control growth for infusion extract, except the hexane extract. With T. hirsuta,
      all the extracts tested (hexane and ethanol-water), except the infusion extract,
      also exhibited antitumor activity (58.2% and 65.5% of control growth
      respectively). The ethanol-water and infusion extracts of A. campestris showed
      higher antioxidant activity, polyphenol and flavonoid contents than those of T.
      hirsuta. These results show that there is a positive correlation between the
      antitumor activity and the antioxidant activity, and of these two activities and
      with the levels of polyphenols and flavonoids. The essential oil and the other
      extracts of A. campestris, which exhibited significant antitumor activity against
      the HT-29 cells deserve further research into the chemoprevention and treatment
      of colon cancer.

PMID- 21075160
TI  - Does 4-methylimidazole have tumor preventive activity in the rat?
AB  - 4-Methylimidazole (4-MEI) is found in a wide array of food products. The National
      Toxicology Program (NTP) recently conducted a two-year feeding cancer bioassay of
      4-MEI in B6C3F(1) mice and F344/N rats. In rats, NTP found "equivocal evidence of
      carcinogenic activity" in females based on increased incidences of mononuclear
      cell leukemia and "no evidence of carcinogenic activity" in males. However, dose
      related, statistically significant decreases in multiple tumors were observed in
      both male and female rats exposed to 4-MEI in the NTP bioassay. For example, 4
      MEI was associated with a 25-fold decrease in the incidence of mammary tumors
      among high dose females. NTP noted briefly that the decreases in certain tumors,
      including mammary tumors, were greater than could be attributed to body weight
      alone. The present paper provides a more detailed evaluation of the evidence that
      4-MEI exhibits tumor preventive activity in the rat based upon the results of the
      NTP bioassay. Reduced body weight offers a partial explanation for the reduction
      in tumors, but does not appear to be the primary cause of the decreased tumor
      incidences, indicating that 4-MEI itself may possess an ability to prevent tumor
      formation.

PMID- 21075161
TI  - Synephrine: from trace concentrations to massive consumption in weight-loss.
AB  - Synephrine is cited as 'the active component' of plants and dietary supplements
      used in weight loss. It became one of the most popular stimulants present in
      weight-loss products after the US Food and Drug Administration had interdicted
      the use of ephedrine-containing dietary supplements. Synephrine is also a trace
      amine that can be found in vertebrates and invertebrates. Synephrine acts on
      several adrenergic and serotonergic receptors and its activity on trace-amine
      associated receptors has long been discussed. Synephrine exists in three
      different positional isomers; however, only p- and m-synephrine have been
      described in weight-loss products. The alleged effectiveness of synephrine
      containing supplements is attributed to the thermogenic effects arising from
      synephrine's adrenergic stimulation. The growing use of synephrine has raised
      concerns since it has been accompanied by reports of adverse effects. Cardiac
      adverse events, including hypertension, tachyarrhythmia, variant angina, cardiac
      arrest, QT prolongation, ventricular fibrillation, myocardial infarction, and
      sudden death, have been the most common adverse effects associated with
      synephrine intake. The mechanisms involved in synephrine-induced cardiotoxicity
      are still unknown since studies related to its safety are scarce. This review
      will address general aspects concerning the pharmacology of synephrine, but will
      focus on the efficacy and toxicity aspects related to the use of synephrine in
      weight-loss.

PMID- 21075162
TI  - High efficacy of anti DBL4E-VAR2CSA antibodies in inhibition of CSA-binding
      Plasmodium falciparum-infected erythrocytes from pregnant women.
AB  - Malaria during pregnancy is a major cause of intra-uterine growth-retardation and
      infant death in sub-Saharan Africa. Ideally, this could be prevented by a vaccine
      delivered before the first pregnancy. Antibodies against domain DBL4E from
      VAR2CSA has been shown to inhibit adhesion of laboratory isolates to the
      placental receptor chondroitin sulfate A. In this study, the binding inhibitory
      efficacy of IgG elicited by two different DBL4E recombinant proteins was tested
      on a panel of fresh clinical isolates from pregnant women living in Benin and
      Tanzania. The most promising recombinant protein elicited antibodies with similar
      efficacy as pooled plasma from immune multi-gravid African women.

PMID- 21075163
TI  - "Once Bitten, Twice Shy": participant perspectives in the aftermath of an early
      HIV vaccine trial termination.
AB  - The Step Study phase IIb HIV-1 vaccine trial was terminated early due to
      futility; subsequent analyses revealed increased susceptibility to HIV infection
      among a subset of test vaccine recipients. We conducted a mixed methods
      investigation, including a brief, self-administered baseline questionnaire and in
      depth, semi-structured, 1-h interviews after unblinding, to explore experiences
      and perspectives among trial participants and key informants. Interviews were
      digitally recorded, transcribed, and analyzed using NVivo and thematic
      techniques. Forty-eight trial participants (46 gay/bisexual men) completed
      baseline surveys; 15 (14 gay/bisexual men) engaged in post-trial interviews.
      Participants indicated surprise and disappointment about the early trial
      termination and unexpected risks. Some articulated understanding the
      uncertainties of clinical trials, steadfast support and willingness to
      participate in the future; others reported greater risks than they deemed
      acceptable and unlikelihood of volunteering again. A few indicated mistrust of
      trial sponsors and ethics. Participants' most profound criticism was not about
      unexpected results, but perceived delays in unblinding and gaps in post-trial
      dissemination of information. Future HIV vaccine trials may benefit from
      increased emphasis on: (1) communication mechanisms among participants,
      investigators and trial sponsors, and (2) post-trial dissemination of information
      and psychosocial support.

PMID- 21075164
TI  - Lessons learnt from pandemic A(H1N1) 2009 influenza vaccination. Highlights of a
      European workshop in Brussels (22 March 2010).
AB  - This European workshop identified a number of lessons learnt in the field of
      vaccine licensure, prioritization of target groups, communication on pandemic
      vaccines, implementation of vaccination and safety monitoring. The mild severity
      of the pandemic A(H1N1) 2009 influenza virus influenced the perception of
      pandemic vaccines, as previous pandemic preparedness had anticipated a more
      virulent virus. This vaccination experience provides an important opportunity for
      research on the long-term immunogenicity and safety of pandemic vaccines in
      pregnant women and children, as well as on the long-term safety of adjuvants.
      Preparedness for future pandemics could involve improved decision-making on
      target groups and increased communication on vaccine safety.

PMID- 21075165
TI  - 7, 8-diacetoxy-4-methylcoumarin induced cell death in human tumor cells is
      influenced by calreticulin.
AB  - Calreticulin (CRT), an endoplasmic reticulum resident protein demonstrates
      transacetylase activity in presence of 7, 8 diacetoxy-4-methyl coumarin (DAMC) in
      vitro. To investigate the possible role of CRT and DAMC mediated protein
      acetylation in cells, we investigated the effects of DAMC in tumor cells with
      different levels of CRT. DAMC was more toxic (clonogenicity, metabolic viability
      and proliferation) to human glioma cells (BMG-1) expressing low endogenous CRT
      level as compared to head and neck carcinoma cells (KB) with a high CRT level.
      The cytotoxicity was accompanied by loss of mitochondrial membrane potential in
      both the cells, which correlated with corresponding changes in the levels of pro
      apoptotic (Bax) and anti-apoptotic (NFkB) regulators. Manipulation of CRT protein
      level in KB cells by application of small RNA interference enhanced the
      sensitivity by four folds while over expression of CRT in BMG-1 cells reduced
      their sensitivity to DAMC by ~20% strongly suggesting the influence of CRT on
      DAMC induced cytotoxicity. The partial rescue of CROE cells from DAMC induced
      toxicity was accompanied by changes in NFkB levels and over all protein
      acetylation status, besides increase in the NADPH-cytochrome c reductase activity
      related to its well known antioxidant property. Since CRT is over-expressed in
      cancer cells, which are generally resistant to radio- and chemotherapy; targeting
      CRT transacetylase system, may be an attractive approach for increasing the
      efficacy of anticancer therapies.

PMID- 21075166
TI  - New insight into the Nox4 subcellular localization in HEK293 cells: first
      monoclonal antibodies against Nox4.
AB  - Nox4, a member of Nox family of NADPH oxidase expressed in nonphagocytic cells,
      is a major source of reactive oxygen species in many cell types. But
      understanding of the role of Nox4 in the production of ROS and of regulation
      mechanism of oxidase activity is largely unknown. This study reports for the
      first time the generation and characterization of 5 mAbs against a recombinant
      Nox4 protein (AA: 206-578). Among 5 novel mAbs, 3 mAbs (8E9, 5F9, 6B11)
      specifically recognized Nox4 protein in HEK293 transfected cells or human kidney
      cortex by western blot analysis; mAb 8E9 reacted with intact tet-induced T-RExTM
      Nox4 cells in FACS studies. The other 2 mAbs 10B4 and 7C9 were shown to have a
      very weak reactivity after purification. Immunofluorescence confocal microscopy
      showed that Nox4 localized not only in the perinuclear and endoplasmic reticulum
      regions but also at the plasma membrane of the cells which was further confirmed
      by TIRF-microscopy. Epitope determination showed that mAb 8E9 recognizes a region
      on the last extracellular loop of Nox4, while mAbs 6B11 and 5F9 are directed to
      its cytosolic tail. Contrary to mAb 6B11, mAb 5F9 failed to detect Nox4 at the
      plasma membrane. Cell-free oxidase assays demonstrated a moderate but significant
      inhibition of constitutive Nox4 activity by mAbs 5F9 and 6B11. In conclusion, 5
      mAbs raised against Nox4 were generated for the first time. 3 of them will
      provide powerful tools for a structure/function relationship of Nox4 and for
      physiopathological investigations in humans.

PMID- 21075167
TI  - Prediction and analysis of protein palmitoylation sites.
AB  - Palmitoylation is a universal and important lipid modification, involving a
      series of basic cellular processes, such as membrane trafficking, protein
      stability and protein aggregation. With the avalanche of new protein sequences
      generated in the post genomic era, it is highly desirable to develop
      computational methods for rapidly and effectively identifying the potential
      palmitoylation sites of uncharacterized proteins so as to timely provide useful
      information for revealing the mechanism of protein palmitoylation. By using the
      Incremental Feature Selection approach based on amino acid factors, conservation,
      disorder feature, and specific features of palmitoylation site, a new predictor
      named IFS-Palm was developed in this regard. The overall success rate thus
      achieved by jackknife test on a newly constructed benchmark dataset was 90.65%.
      It was shown via an in-depth analysis that palmitoylation was intimately
      correlated with the feature of the upstream residue directly adjacent to cysteine
      site as well as the conservation of amino acid cysteine. Meanwhile, the protein
      disorder region might also play an import role in the post-translational
      modification. These findings may provide useful insights for revealing the
      mechanisms of palmitoylation.

PMID- 21075168
TI  - Spatiotemporal dynamics of the Calvin cycle: multistationarity and symmetry
      breaking instabilities.
AB  - The possibility of controlling the Calvin cycle has paramount implications for
      increasing the production of biomass. Multistationarity, as a dynamical feature
      of systems, is the first obvious candidate whose control could find
      biotechnological applications. Here we set out to resolve the debate on the
      multistationarity of the Calvin cycle. Unlike the existing simulation-based
      studies, our approach is based on a sound mathematical framework, chemical
      reaction network theory and algebraic geometry, which results in provable results
      for the investigated model of the Calvin cycle in which we embed a hierarchy of
      realistic kinetic laws. Our theoretical findings demonstrate that there is a
      possibility for multistationarity resulting from two sources, homogeneous and
      inhomogeneous instabilities, which partially settle the debate on multistability
      of the Calvin cycle. In addition, our tractable analytical treatment of the
      bifurcation parameters can be employed in the design of validation experiments.

PMID- 21075169
TI  - Localization and functional activity of cytochrome P450 side chain cleavage
      enzyme (CYP11A1) in the adult rat kidney.
AB  - Cumulative evidence demonstrated effective downstream metabolism of pregnenolone
      in renal tissue. The aim of this study was to evaluate the expression and
      functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1),
      which converts cholesterol into pregnenolone, in adult rat kidney.
      Immunohistochemical labeling for CYP11A1 was observed in renal cortex and
      medulla, on structures identified as distal convoluted tubule and thick ascending
      limb of Henle's loop, respectively. Immunoblotting analysis corroborated the
      renal expression of the protein in inner mitochondrial membrane fractions. The
      incubation of isolated mitochondria with the membrane-permeant cholesterol
      analogue 22R-hydroxycholesterol resulted in efficient formation of pregnenolone,
      the immediate precursor for the synthesis of all the steroid hormones. The low
      progesterone production rate observed in these experiments suggested a poor
      activity of 3beta-hydroxysteroid dehydrogenase enzyme in renal mitochondria. The
      steroidogenic acute regulatory protein (StAR), involved in the mitochondrial
      import of cholesterol, was detected in renal tissue at both mRNA and protein
      level. Immunostaining for StAR showed similar distribution to that observed for
      CYP11A1. The expression of StAR and CYP11A1 was found to be higher in medulla
      than in cortex. This enhanced expression of steroidogenesis-related proteins
      correlated with a greater pregnenolone synthesis rate and higher steroid hormones
      tissular content measured in medulla. In conclusion, we have established the
      expression and localization of StAR and CYP11A1 protein, the ability of
      synthesizing pregnenolone and a region-specific content of sex hormones in the
      adult rat kidney. These data clearly show that the kidney is a steroid hormones
      synthesizing organ. It is proposed that the existence in the kidney of complete
      steroidogenic machinery would respond to a physiological significance.

PMID- 21075171
TI  - Lack of effects of low frequency repetitive transcranial magnetic stimulation on
      alpha rhythm phase synchronization in migraine patients.
AB  - The study aimed to test the modulation induced by 1 Hz repetitive Transcranial
      Magnetic Stimulation (rTMS) of the occipital cortex on the alpha phase
      synchronization under repetitive flash stimuli in 15 migraine without aura
      patients compared to 10 controls. The EEG was recorded by 7 channels, while flash
      stimuli were delivered at 9, 18, 21 and 24 Hz in basal, rTMS (15 min of 1 Hz
      stimulation of the occipital cortex) and sham conditions. Migraine patients
      displayed increased alpha-band phase synchronization under visual stimulation,
      while an overall desynchronizing effect was evident in controls. The rTMS
      resulted in a slight increase of synchronization index in migraine patients,
      which did not cause significant differences in respect to the basal and sham
      conditions. The synchronizing-desynchronizing changes of alpha rhythm under
      repetitive flash stimulation, seem independent from the state of occipital cortex
      excitability. Other mechanisms beyond cortical excitability may contribute to
      explain migraine pathogenesis.

PMID- 21075172
TI  - Recovery of motor performance deterioration induced by a demanding finger motor
      task does not follow cortical excitability dynamics.
AB  - The performance of a demanding exercise can result in motor performance
      deterioration and depression of primary motor cortex excitability. In the present
      work we defined a motor task that requires measurable skilled performance to
      unveil motor performance changes during the execution of a demanding task and to
      investigate the dynamics of motor performance and cortical excitability changes
      in absence of overt peripheral fatigue. Twenty-one normal subjects, divided into
      three groups were asked to perform a sequence of finger opposition movements
      (SEQ) paced at 2 Hz for 5 min, quantitatively evaluated by means of a sensor
      engineered glove able to perform a spatio-temporal analysis of motor performance.
      Maximal voluntary contraction (MVC) was evaluated before and after the motor task
      in group 1 while motor evoked potentials (MEP) were evaluated before and after
      the motor task in group 2 and 3. Group 1 and 2 performed the 5 min-SEQ while
      group 3 was asked to perform the 5 min-SEQ twice to assess the dynamics of motor
      performance and cortical excitability. As a result, we found that the execution
      of 5 min-SEQ induced motor performance deterioration associated with no change in
      MVC but a decrease in cortical excitability. We further found that the dynamics
      of cortical excitability and motor performance were different. In fact, a short
      rest period (i.e., period necessary to collect MEP) between the execution of two
      5 min-SEQs was able to recover the motor performance but not the cortical
      excitability. Finally, no change in spinal excitability was observed. These
      findings suggest that although primary motor cortex seems to be mainly involved
      in motor performance deterioration during the execution of a demanding finger
      motor task, the recovery of motor performance does not follow cortical
      excitability dynamics.

PMID- 21075170
TI  - Recruitment of the oncoprotein v-ErbA to aggresomes.
AB  - Aggresome formation, a cellular response to misfolded protein aggregates, is
      linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v
      ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRalpha1),
      accumulates in and sequesters TRalpha1 into cytoplasmic foci. Here, we show that
      foci represent v-ErbA targeting to aggresomes. v-ErbA colocalizes with aggresomal
      markers, proteasomes, hsp70, HDAC6, and mitochondria. Foci have hallmark
      characteristics of aggresomes: formation is microtubule-dependent, accelerated by
      proteasome inhibitors, and they disrupt intermediate filaments. Proteasome
      mediated degradation is critical for clearance of v-ErbA and T(3)-dependent
      TRalpha1 clearance. Our studies highlight v-ErbA's complex mode of action: the
      oncoprotein is highly mobile and trafficks between the nucleus, cytoplasm, and
      aggresome, carrying out distinct activities within each compartment. Dynamic
      trafficking to aggresomes contributes to the dominant negative activity of v-ErbA
      and may be enhanced by the viral Gag sequence. These studies provide insight into
      novel modes of oncogenesis across multiple cellular compartments.

PMID- 21075173
TI  - Gaze modulates non-propositional reasoning: further evidence for spatial
      representation of reasoning premises.
AB  - Human and animals are able to decide that A>C after having learnt that A>B and
      B>C. This basic property of logical thinking has been studied by transitive
      inference (TI) tasks. It has been hypothesized that subjects displace the
      premises of the inference on a mental line to solve the task. An evidence in
      favor of this interpretation is the observation of the symbolic distance effect,
      that is the improvement of the performance as the distance between items
      increases. This effect has been interpreted as support to the hypothesis that
      ability to perform TI tasks follows the same rules and is mediated by the same
      brain circuits involved in the performance of spatial tasks. We tested ten
      subjects performing a TI on an ordered list of Japanese characters while they
      were fixating either leftwards or rightwards, to evaluate whether the eye
      position modulated the performance in making TI as it does in spatial tasks. Our
      results show a significant linear decrease of the reaction time with the increase
      of the symbolic distance and a shift of this trend towards lower reaction times
      when subjects were fixating to the left. We interpret this eye position effect as
      a further evidence that spatial and reasoning tasks share the same underlying
      mechanisms and neural substrates. The eye position effect also points to a
      parietal cortex involvement in the neural circuit involved in transitive
      reasoning.

PMID- 21075174
TI  - Arrestin-1 expression level in rods: balancing functional performance and
      photoreceptor health.
AB  - In rod photoreceptors, signaling persists as long as rhodopsin remains
      catalytically active. Phosphorylation by rhodopsin kinase followed by arrestin-1
      binding completely deactivates rhodopsin. Timely termination prevents excessive
      signaling and ensures rapid recovery. Mouse rods express arrestin-1 and rhodopsin
      at ~0.8:1 ratio, making arrestin-1 the second most abundant protein in the rod.
      The biological significance of wild type arrestin-1 expression level remains
      unclear. Here we investigated the effects of varying arrestin-1 expression on its
      intracellular distribution in dark-adapted photoreceptors, rod functional
      performance, recovery kinetics, and morphology. We found that rod outer segments
      isolated from dark-adapted animals expressing arrestin-1 at wild type or higher
      level contain much greater fraction of arrestin-1 than previously estimated, 15
      25% of the total. The fraction of arrestin-1 residing in the outer segments (OS)
      in animals with low expression (4-12% of wild type) is much lower, 5-7% of the
      total. Only 4% of wild type arrestin-1 level in the outer segments was sufficient
      to maintain near-normal retinal morphology, whereas rapid recovery required at
      least ~12%. Supra-physiological arrestin-1 expression improved light sensitivity
      and facilitated photoresponse recovery, but was detrimental for photoreceptor
      health, particularly in the peripheral retina. Thus, physiological level of
      arrestin-1 expression in rods reflects the balance between short-term functional
      performance of photoreceptors and their long-term health.

PMID- 21075176
TI  - Protective effect of flavonoids from Astragalus complanatus on radiation induced
      damages in mice.
AB  - This study aimed to evaluate the radioprotective effect of flavonoids extracted
      from the seeds of Astragalus complanatus R.Br. (FAC) and their protective
      mechanism against radiation damage. FAC increased the survival rate of mice and
      made the damaged organ injured by (60)Co gamma-irradiation recovered to normal
      appearance with the mechanism of enhancing immune function and blood-producing
      function in vivo. The molecule mechanism of FAC against radiation is involved in
      the reduction of DNA injury and mutation in vitro. Eleven monomers of the FAC
      were analyzed by HPLC. These results seem to support the use of FAC in relieving
      radiation damage.

PMID- 21075175
TI  - Novel mechanism of increased Ca2+ release following oxidative stress in neuronal
      cells involves type 2 inositol-1,4,5-trisphosphate receptors.
AB  - Dysregulation of Ca(2+) signaling following oxidative stress is an important
      pathophysiological mechanism of many chronic neurodegenerative disorders,
      including Alzheimer's disease, age-related macular degeneration, glaucomatous and
      diabetic retinopathies. However, the underlying mechanisms of disturbed
      intracellular Ca(2+) signaling remain largely unknown. We here describe a novel
      mechanism for increased intracellular Ca(2+) release following oxidative stress
      in a neuronal cell line. Using an experimental approach that included
      quantitative polymerase chain reaction, quantitative immunoblotting,
      microfluorimetry and the optical imaging of intracellular Ca(2+) release, we show
      that sub-lethal tert-butyl hydroperoxide-mediated oxidative stress result in a
      selective up-regulation of type-2 inositol-1,4,5,-trisphophate receptors. This
      oxidative stress mediated change was detected both at the transcriptional and
      translational level and functionally resulted in increased Ca(2+) release into
      the nucleoplasm from the membranes of the nuclear envelope at a given receptor
      specific stimulus. Our data describe a novel source of Ca(2+) dysregulation
      induced by oxidative stress with potential relevance for differential subcellular
      Ca(2+) signaling specifically within the nucleus and the development of novel
      neuroprotective strategies in neurodegenerative disorders.

PMID- 21075177
TI  - Synergy research: approaching a new generation of phytopharmaceuticals.
AB  - The longstanding, successful use of herbal drug combinations in traditional
      medicine demands that we find a rationale for their comparative pharmacological
      and therapeutic superiority to isolated single constituents. The synergistic
      efficacy of these combinations can be evaluated and verified by Berenbaum's
      isobole method, followed by clinical studies performed in comparison with
      synthetic standard drugs. There are many examples of mono- and multi-extract
      combinations used presently, which exhibit synergistic efficiency based on multi
      target mechanisms of action. Among the natural products, gallocatechins of green
      tea and curcuminoids of ginger are the presently favoured polyphenols for a
      possible future use in co-medication with antibiotics and standard anticancer
      drugs. The main targets were found to be COX 1+2, NF-kappaB, and membrane
      glycoproteins that belong to the ATP-binding cassette (ABC) transporter family.

PMID- 21075178
TI  - The National Institutes of Health investment in research on botanicals.
AB  - The Office of Dietary Supplements (ODS) and the National Center for Complementary
      and Alternative Medicine (NCCAM) were both established by Congress in the 1990s.
      ODS aims to strengthen knowledge and understanding of dietary supplements (DS).
      NCCAM promotes exploration of complementary and alternative medicine in the
      context of rigorous science. Together, they developed the Botanical Research
      Centers Program to promote interdisciplinary study of botanicals, particularly
      those found in DS, by supporting research activities ranging from plant and
      characterization to preclinical and early-phase clinical studies. These Centers
      are part of the coordinated efforts of ODS and NCCAM to enhance botanical
      research.

PMID- 21075179
TI  - Three new bis-styryllactones from Goniothalamus cheliensis.
AB  - Three new bis-styryllactone analogues, goniolactones G-I (1-3), have been
      isolated from the root barks of Goniothalamus cheliensis. Their structures were
      established on the basis of extensive spectroscopic investigation including HR
      ESI-MS and 2D NMR (HSQC, HMBC, (1)H-(1)H COSY, ROESY).

PMID- 21075180
TI  - Anticholinesterase activity of standardized extract of Illicium verum Hook. f.
      fruits.
AB  - Illicium verum is a well known spice in traditional Indian system for its
      therapeutic potential. The present study was aimed to evaluate the
      acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory (BChE) activity
      of standardized extracts of I. verum and its oil. Present study confirmed that
      anethole contributed to the anticholinesterase activity of I. verum, with more
      specificity towards AChE. IC(50) for AChE and BChE inhibitory activity of
      anethole was 39.89+/-0.32 MUg/mL and 75.35+/-1.47 MUg/mL, whereas for the oil,
      36.00+/-0.44 MUg/mL and 70.65+/-0.96 MUg/mL respectively. Therefore I. verum can
      be a good lead as anti-cholinesterase agent from natural resources.

PMID- 21075181
TI  - Intestinal absorption of forsythoside A in different compositions of Shuang-Huang
      Lian.
AB  - Shuang-Huang-Lian (SHL), a traditional Chinese formula containing Lonicerae
      japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is
      commonly used to treat acute upper respiratory tract infection, acute bronchitis
      and light pneumonia. Forsythoside A is one of the main active ingredients in
      Forsythiae fructus, a key herb in SHL. In the present study, effects of different
      compositions in SHL on the intestinal absorption of forsythoside A were
      investigated. The observations from in situ intestinal circulation model showed
      that A/%(h(-1)) of forsythoside A in FF+LSF, FF+SR and SHL were all reduced
      greatly compared with that in FF. However, in pharmacokinetics study, C(max) and
      AUC(0->1440) of forsythoside A all increased and T(1/2) prolonged in SHL, FF+LJF
      and FF+SR compared with FF. The results indicated that the different compositions
      of SHL decreased absorption but increased bioavailability of forsythoside A,
      which may be related to its metabolism inhibited in intestine or liver.

PMID- 21075182
TI  - Vegetable-borne nitrate and nitrite and the risk of methaemoglobinaemia.
AB  - High levels of nitrate in vegetables are frequently reported. The potential
      hazard of vegetable-borne nitrate is from its conversion to methaemoglobin
      producing nitrite before and/or after ingestion. Methaemoglobin cannot bind
      oxygen and produces a leftward shift in oxygen-dissociation curve, causing
      hypoxaemia. Infants under 3 months old are particularly susceptible to
      methaemoglobinaemia. Older infants and children are also at risk. Adults are not
      thought to be at risk of vegetable-borne nitrate or nitrite induced
      methaemoglobinaemia. This view should now change if the high nitrate levels in
      some vegetables and the effects of storage and food processing on its conversion
      to nitrite are taken into consideration. In fresh, undamaged vegetables, the
      nitrite concentrations are usually very low. Under adverse post-harvest storage
      conditions, nitrite concentrations in vegetables increase as a result of
      bacterial contamination and endogenous nitrate reductase action. Nitrite
      accumulation in vegetables is inhibited under frozen storage because endogenous
      nitrate reductase is inactivated. Pureeing releases endogenous nitrate reductase,
      increasing nitrite concentrations in vegetables. Oral reduction of nitrate is the
      most important source of nitrite. In order to maximise the health benefits from
      eating vegetables, measures should be taken to reduce the nitrate and nitrite
      exposures while maintaining the recommended vegetable intake. Excessive use of
      nitrogen fertilizers should be avoided so as to reduce nitrate build up in soil
      or vegetables. Vegetables must be stored and processed properly to prevent
      bacteria contamination. Removal of stem and midrib results in a decrease of
      nitrate content in lettuce and spinach. Peeling of potatoes and beetroot
      decreases the nitrate content. Nitrate levels in some vegetables can decrease
      after cooking in water or blanching. Home prepared infant food containing
      vegetables should be avoided until the infant is 3 months or older.

PMID- 21075183
TI  - Semisynthesis and pharmacological investigation of lipo-alkaloids prepared from
      aconitine.
AB  - Processed aconite drugs are widely used in Eastern medicine as painkillers and
      antirheumatic agents. It is known that the traditional processing of aconite
      drugs increases the amount of lipo-alkaloids. In order to obtain information
      about the pharmacological potential of these compounds, semisynthesis of 9
      aconitine-derived lipo-alkaloids was carried out and their COX-1, COX-2 and
      LTB(4) formation inhibitory activities were investigated. It was found that
      compounds esterified with unsaturated fatty acids demonstrated significant COX-2
      inhibitory effects, while in the COX-1 assay only 14-benzoylaconine-8-O
      eicosapentaenoate exerted remarkable activity. The inhibition of LTB(4) formation
      was pronounced in cases of long chain fatty acid derivatives.

PMID- 21075184
TI  - Magnetic microparticles based on natural polymers.
AB  - Magnetic micro- and nanoparticles based on ferrofluid (maghemite) were elaborated
      by inverse emulsion crosslinking of sodium salt of carboxymethylcellulose (CMCNa)
      and gelatin. Crosslinking was carried out with glutaric aldehyde within aqueous
      droplets dispersed into toluene in presence of surfactants. The influence of
      parameters such as the ratio of polymers and maghemite in the initial mixture on
      the composition, size, size dispersity, particle swelling and their ability for
      drug inclusion was studied. The ability to take-up drugs is directly correlated
      with the degree of swelling and gelatin content within the particles. Particle
      size is between tens of nanometers and a few microns. The magnetic properties of
      particles are demonstrated from saturation magnetization (between 43 and 44 emu
      g(-1)) when their superparamagnetic character was shown by the absence of
      hysteresis on the magnetization curve. Polymer-drug systems elaborated under
      particles keep their bactericide activity for at least 48 h. The absence of
      toxicity, associated with the bactericide activity, make these systems potential
      drug carriers.

PMID- 21075185
TI  - Perivascular sirolimus-delivery system.
AB  - Autologous vein grafts are often used for treating damaged vessels, e.g.
      arteriovenous fistulas or arterial bypass conduits. Veins have a different
      histological structure from arteries, which often leads to intimal hyperplasia
      and graft restenosis. The aim of this study was to develop a perivascular
      sirolimus-delivery system that would release the antiproliferative drug sirolimus
      in a controlled manner. Polyester Mesh I was coated with purasorb, i.e. a
      copolymer of L-lactide and E-caprolactone, with dissolved sirolimus; Mesh II was
      coated with two copolymer layers; the layer with dissolved sirolimus was overlaid
      with pure purasorb. This arrangement allowed sirolimus to be released for 6 and 4
      weeks, for Mesh I and Mesh II, respectively. Mesh II released sirolimus more
      homogeneously, without the initial burst effect during the first week. However,
      the cumulative release curve was steeper at later time points than the curve for
      Mesh I. Both meshes inhibited proliferation of rat vascular smooth muscle cells
      during 14-day culture in vitro and preserved excellent cell viability. Newly
      developed sirolimus-releasing perivascular meshes are promising devices for
      preventing autologous graft restenosis.

PMID- 21075186
TI  - Photometric imaging in particle size measurement and surface visualization.
AB  - The aim of this paper is to give an insight into photometric particle sizing
      approaches, which differ from the typical particle size measurement of dispersed
      particles. These approaches can often be advantageous especially for samples that
      are moist or cohesive, when dispersion of particles is difficult or sometimes
      impossible. The main focus of this paper is in the use of photometric stereo
      imaging. The technique allows the reconstruction of three-dimensional images of
      objects using multiple light sources in illumination. The use of photometric
      techniques is demonstrated in at-line measurement of granules and on-line
      measurement during granulation and dry milling. Also, surface visualization and
      roughness measurements are briefly discussed.

PMID- 21075187
TI  - Inner ear biocompatibility of lipid nanocapsules after round window membrane
      application.
AB  - Nanoparticle-mediated drug delivery represents the future in terms of treating
      inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to
      pass though the round window membrane (RWM) and reached the spiral ganglion cells
      and nerve fibers, among other cell types in the inner ear. The present study
      aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact
      round window membrane delivery in rats. The primary cochlear cells and mouse
      fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo
      study showed that administration of LNCs did not cause hearing loss, nanoparticle
      application-related cell death, or morphological changes in the inner ear, at up
      to 28 days of observation. The cochlear neural elements, such as synaptophysin,
      ribbon synapses, and S-100, were not affected by the administration of LNCs.
      However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve
      in osseous spiral lamina canal after LNC delivery, a phenomenon that requires
      further investigation. LNCs are potential vectors for the delivery of drugs to
      the inner ear.

PMID- 21075188
TI  - Dangguijakyak-san, a medicinal herbal formula, protects dopaminergic neurons from
      6-hydroxydopamine-induced neurotoxicity.
AB  - AIM OF THE STUDY: Dangguijakyak-san (DJS) is a multi-herbal formula that has long
      been widely used in traditional Oriental medicine to treat gynecologic disorders,
      including neurological symptoms. Recent clinical and experimental studies have
      reported aging and anti-neurodegenerative effects of DJS. In this study, we
      evaluated the neuroprotective effects of DJS on dopaminergic (DA) neurons damaged
      by 6-hydroxydopamine (6-OHDA). MATERIALS AND METHODS: To evaluate the protective
      effects of DJS, we analyzed viability in SH-SY5Y neuroblastoma cells and tyrosine
      hydroxylase (TH) staining in primary DA cells. To explore the possible
      mechanism(s) of neuroprotection, we assessed anti-oxidant activity by measuring
      reactive oxygen species (ROS) and glutathione (GSH) levels. To determine
      mitochondria-mediated apoptotic activity, we examined mitochondrial membrane
      potential, cytochrome c release, and caspase-3 activation. RESULTS: DJS at 0.05-5
      MUg/mL significantly protected SH-SY5Y cells from 6-OHDA toxicity, dose
      dependently, and attenuated 6-OHDA damage in primary DA cells. DJS reduced 6-OHDA
      induced intracellular ROS production and GSH depletion and inhibited
      mitochondrial membrane instability, cytosolic cytochrome c release, and caspase-3
      activation. CONCLUSIONS: These results demonstrate that DJS has neuroprotective
      effects in DA neurons against 6-OHDA-induced toxicity through anti-oxidant and
      anti-mitochondrial-mediated apoptotic activities.

PMID- 21075189
TI  - Taraxacum officinale Weber extracts inhibit LPS-induced oxidative stress and
      nitric oxide production via the NF-kappaB modulation in RAW 264.7 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The common dandelion (Taraxacum officinale G.H.
      Weber ex Wiggers, Asteraceae) has been widely used in folklore medicine to treat
      dyspepsia, heartburn, and spleen and liver disorders. AIM OF THE STUDY: To
      compare the antioxidative and anti-inflammatory activities of Taraxacum
      officinale methanol extract (TOME) and water extract (TOWE) in lipopolysaccharide
      (LPS)-stimulated RAW 264.7 cells and assess their constitutional differences,
      including luteolin, chicoric acid, and total phenol content. MATERIALS AND
      METHODS: Antioxidative enzyme activities, nitric oxide (NO) production, and
      inducible NO synthase (iNOS) and nuclear factor (NF)-kappaB expression were
      estimated by biochemical analysis, the Griess reaction, reverse transcription
      polymerase chain reaction, western hybridization, and electrophoretic mobility
      shift assay. High-performance liquid chromatography and the Folin-Ciocalteau
      method were used to analyze functional phytochemicals and total phenol content.
      RESULTS: TOME and TOWE significantly reduced NO production with an IC(50) of 79.9
      and 157.5 MUg/mL, respectively, without cytotoxicity. Depleted glutathione (GSH)
      and antioxidative enzyme activities, including superoxide dismutase, catalase,
      GSH-peroxidase, and GSH-reductase, were restored by dandelion extracts. Both
      extracts inhibited LPS-stimulated iNOS gene expression and that of its
      transcription factor, NF-kappaB, in parallel with nitrite reduction. TOME showed
      more potent antioxidative and anti-inflammatory capacities than TOWE, which was
      attributable to its high total phenol, luteolin, and chicoric acid content.
      CONCLUSIONS: These results indicate that TOME and TOWE inhibit oxidative stress
      and inflammatory responses through elevated de novo synthesis of antioxidative
      enzymes and suppression of iNOS expression by NF-kappaB inactivation.

PMID- 21075190
TI  - The aqueous extract of Terminalia superba (Combretaceae) prevents glucose-induced
      hypertension in rats.
AB  - AIM OF THE STUDY: The stem bark of Terminalia superba (Combretaceae) (TS) is used
      in traditional Cameroonian medicine as antihypertensive remedy. The aim of this
      study was to investigate the hypotensive and the antihypertensive effects of the
      aqueous extract of the stem bark of Terminalia superba. MATERIALS AND METHODS:
      Hypertension was obtained in rats by oral administration of 10% D-glucose for 3
      weeks. The acute effects of Terminalia superba were studied on blood pressure
      (BP) and heart rate (HR) after intravenous administration in normotensive rats
      (NTR) and glucose hypertensive rats (GHR). The antihypertensive effects were
      studied after oral administration of the extract (50 and 100 mg/kg/day) or
      nifedipine (10 mg/kg/day) for 3 weeks. At the end of the experiment, BP and HR
      were measured and reduced glutathione (GSH), malondialdehyde (MDA) and superoxide
      dismutase (SOD) activity levels were measured in heart, aorta, liver and kidney.
      RESULTS: Intravenous administration of the aqueous extract of Terminalia superba
      induced a significant hypotensive response without any change in HR. The
      hypotensive effect of the extract was unaffected by atropine or propranolol but
      decreased by reserpine (5 mg/kg) and yohimbine (0.1 mg/kg). In addition, the oral
      administration of the extract significantly prevented the rise in BP in glucose
      hypertensive rats. Finally, the treatment with plant extract significantly
      blunted the decrease in GSH and the increase in MDA levels associated with
      hypertension, and significantly prevents the increase in aortic SOD activity.
      CONCLUSIONS: The present study demonstrates that the aqueous extract of the stem
      bark of Terminalia superba exhibits hypotensive and anti-hypertensive properties
      that are, at least in part, related to a withdrawal of sympathetic tone and to an
      improvement of the antioxidant status, respectively. Overall data validate the
      use of Terminalia superba as antihypertensive therapy in traditional medicine.

PMID- 21075191
TI  - Antiplasmodial and cytotoxic activities of medicinal plants traditionally used in
      the village of Kiohima, Uganda.
AB  - AIM OF THE STUDY: In Uganda, malaria is the most common disease and Ugandan
      people largely rely on traditional medicine. In this context, we carried out an
      ethnobotanical study on the Kiohima village, located close to the Kibale National
      Park in South-Western Uganda and investigated in vitro the antiplasmodial and
      cytotoxic activities of selected medicinal plants. MATERIALS AND METHODS: Seventy
      five plants-using adults (men and women) were interviewed to find out their plant
      use. From these information, 48 plants used in traditional medicine were
      identified and according to their reported uses and to bibliographic data,
      several parts of 28 plants (leaves, barks, roots), were selected and collected
      for biological evaluations. These samples were dried, extracted with ethyl
      acetate and the crude extracts were assayed for in vitro antiplasmodial and
      cytotoxic activities at 10 MUg/mL. RESULTS: One third of the screened plants
      showed a significant antiplasmodial activity with inhibition greater than 50% at
      10 MUg/mL. CONCLUSION: These results may indicate a possible explanation of the
      use of some medicinal plant against malaria in the village of Kiohima and have
      also allowed to highlight a plant with potent antimalarial activity: Citropsis
      articulata root barks.

PMID- 21075192
TI  - Cymbopogon citratus as source of new and safe anti-inflammatory drugs: bio-guided
      assay using lipopolysaccharide-stimulated macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extracts of Cymbopogon citratus (Cy)
      leaves are used in traditional medicine for the treatment of inflammatory
      conditions, however, little is known about their mechanism of action. AIM OF THE
      STUDY: The aim of this study is to explore the anti-inflammatory properties of
      Cymbopogon citratus leaves and their polyphenol-rich fractions (PFs), as well its
      mechanism of action in murine macrophages. MATERIALS AND METHODS: A lipid- and
      essential oil-free infusion of Cy leaves was prepared (Cy extract) and
      fractionated by column chromatography. Anti-inflammatory properties of Cy extract
      (1.115 mg/ml) and its PFs, namely phenolic acids (530 MUg/ml), flavonoids (97.5
      MUg/ml) and tannins (78 MUg/ml), were investigated using lipopolysaccharide (LPS)
      stimulated Raw 264.7 macrophages as in vitro model. As inflammatory parameters,
      nitric oxide (NO) production was evaluated by Griess reaction, as well as effects
      on cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) expression and on
      intracellular signaling pathways activation, which were analyzed by Western blot
      using specific antibodies. RESULTS: Cy extract inhibited iNOS expression, NO
      production and various LPS-induced pathways like p38 mitogen-activated protein
      kinase (MAPK), c-jun NH(2)-terminal kinase (JNK) 1/2 and the transcription
      nuclear factor (NF)-kappaB. The extracellular signal-regulated kinase (ERK) 1/2
      and the phosphatidylinositol-3-kinase (PI3K)/Akt activation were not affected by
      Cy extract. Both phenolic acid- and tannin-rich fractions significantly inhibited
      NF-kappaB activation, iNOS expression and NO production but none of the PFs
      modulated MAPKs or PI3K/Akt activation. Neither Cy extract nor PFs affected LPS
      induced COX-2 expression but LPS-induced PGE(2) production is inhibited by Cy
      extract and by phenolic acid-rich fraction. CONCLUSIONS: Our data provide
      evidence that support the usage of Cymbopogon citratus leaves extract in
      traditional medicine, and suggest that Cy, in particular its polyphenolic
      compounds, could constitute a natural source of a new and safe anti-inflammatory
      drug.

PMID- 21075193
TI  - Investigation of in vitro and in vivo anti-asthmatic properties of Siphonochilus
      aethiopicus.
AB  - AIM OF THE STUDY: Asthma is a chronic inflammatory disease of the lungs,
      characterized by increased sensitivity to bronchoconstriction associated with
      infiltration of immune cells, mucus hypersecretion and structural remodelling of
      the airways. In South Africa, the indigenous plant Siphonochilus aethiopicus, is
      used by traditional health practitioners to treat colds, wheezing of the chest,
      coughs, influenza, sinus problems and mild asthma. In this study we aimed to
      investigate the potential anti-inflammatory and anti-allergic properties of S.
      aethiopicus in vitro and its efficacy in a mouse model of allergic asthma.
      MATERIALS AND METHODS: The dried and powdered S. aethiopicus plant material was
      extracted separately with organic solvents (diethyl ether, ethanol) and water.
      Dried extracts as well as a purified furanoterpenoid compound present in the
      extracts were screened in vitro in a glucocorticoid and histamine H(1) receptor
      binding assay and a phosphodiesterase IV enzyme inhibition assay. Extracts were
      also evaluated for efficacy against ovalbumin (OVA)-induced allergic airway
      disease in mice. RESULTS: Biological assaying of extracts of the plant and the
      isolated furanoterpenoid showed significant in vitro inhibition of glucocorticoid
      and histamine H(1) receptor binding and phosphodiesterase IV activity, supporting
      a possible anti-inflammatory, anti-allergic and bronchodilatory effect.
      Administration of S. aethiopicus extracts to OVA-sensitized and challenged mice
      significantly reduced lung inflammation and the percentage of eosinophils in
      bronchoalveolar lavage fluid but did not influence airway hyperreactivity.
      CONCLUSION: This study provides evidence that S. aethiopicus has anti
      inflammatory and anti-allergic properties in vitro and in vivo. These findings
      may support anecdotal accounts of its effectiveness against asthma, sinusitis,
      colds and flu.

PMID- 21075194
TI  - Different sugar residues of the lipopolysaccharide outer core are required for
      early interactions of Salmonella enterica serovars Typhi and Typhimurium with
      epithelial cells.
AB  - The role of lipopolysaccharide (LPS) in entry of Salmonella Typhimurium into
      epithelial cells remains unclear. In this study, we tested the ability of a
      series of mutants with deletions in genes for the synthesis and assembly of the O
      antigen and the outer core of LPS to adhere to and invade HeLa, BHK, and IB3
      epithelial cells lines. Mutants devoid of O antigen, or that synthesized only one
      O antigen unit, or with altered O antigen chain lengths were as able as the wild
      type to enter epithelial cells, indicating that this polysaccharide is not
      required for invasion of epithelial cells in vitro. In contrast, the LPS core
      plays a role in the interaction of S. Typhimurium with epithelial cells. The
      minimal core structure required for adherence and invasion comprised the inner
      core and residues Glc I-Gal I of the outer core. A mutant of S. Typhimurium that
      produced a truncated LPS core lacking the terminal galactose residue had a
      significant lower level of adherence to and ingestion by the three epithelial
      cell lines than did strains with this characteristic. Complementation of the LPS
      production defect recovered invasion to parental levels. Heat-killed bacteria
      with a core composed of Glc I-Gal I, but not bacteria with a core composed of Glc
      I, inhibited uptake of the wild type by HeLa cells. A comparison of the chemical
      structure of the S. Typhi core with the published chemical structure of that of
      S. Typhimurium indicated that the Glc I-Gal I-Glc II backbone is conserved in
      both serovars. However, S. Typhi requires a terminal glucose for maximal
      invasion. Therefore, our data indicate that critical saccharide residues of the
      outer core play different roles in the early interactions of serovars Typhi and
      Typhimurium with epithelial cells.

PMID- 21075195
TI  - Virulence characteristics of translocating Escherichia coli and the interleukin-8
      response to infection.
AB  - Four efficiently translocating Escherichia coli (TEC) strains isolated from the
      blood of humans (HMLN-1), pigs (PC-1) and rats (KIC-1 and KIC-2) were tested for
      their ability to adhere and translocate across human gut epithelial Caco-2 and HT
      29 cells, to elicit a proinflammatory response and for the presence of 47
      pathogenic E. coli virulence genes. HMLN-1 and PC-1 were more efficient in
      adhesion and translocation than rat strains, had identical biochemical phenotype
      (BPT) and serotype (O77:H18) and phylogenetic group (D). KIC-2 adhered more than
      KIC-1, belonged to different BPT and serotype but the same phylogenetic group as
      KIC-1. TEC strains elicited significantly higher IL-8 response in both cell lines
      (P < 0.05) and monocytic THP-1 (P < 0.0001) cells than non-TEC strains. KIC-2
      induced the highest IL-8 response which may be associated with its
      immunostimulatory flagellin. Apart from adhesin genes fimH and bmaE that were
      carried by all strains, HMLN-1 and PC-1 carried capsule synthesis gene kpsMT III
      and KIC-2 carried the EAST1 toxin gene. The lack of known virulence genes and the
      ability of TEC to efficiently adhere and translocate whilst causing
      proinflammatory response suggests that these strains may carry as yet
      unidentified genes that enable their translocating ability.

PMID- 21075196
TI  - Oral biofilm challenge regulates the RANKL-OPG system in periodontal ligament and
      dental pulp cells.
AB  - Inflammatory bone destruction triggered by oral bacteria is a hallmark of chronic
      and apical periodontitis. Receptor activator of NF-kappaB ligand (RANKL)
      activates bone resorption, whereas osteoprotegerin (OPG) blocks its action. These
      are members of the tumor necrosis factor ligand and receptor families,
      respectively. Although individual oral pathogens are known to regulate RANKL and
      OPG expression in cells of relevance to the respective diseases, such as
      periodontal ligament (PDL) and dental pulp (DP) cells, the effect of
      polymicrobial oral biofilms is not known. This study aimed to investigate the
      effect of the Zurich in vitro supragingival biofilm model on RANKL and OPG gene
      expression, in human PDL and DP cell cultures, by quantitative real-time
      polymerase chain reaction. RANKL expression was more pronouncedly up-regulated in
      DP than PDL cells (4-fold greater), whereas OPG was up-regulated to a similar
      extent. The RANKL/OPG ratio was increased only in DP cells, indicating an
      enhanced capacity for inducing bone resorption. The expression of pro
      inflammatory cytokine interleukin-1beta was also increased in DP, but not PDL
      cells. Collectively, the high responsiveness of DP, but not PDL cells to the
      supragingival biofilm challenge could constitute a putative pathogenic mechanism
      for apical periodontitis, which may not crucial for chronic periodontitis.

PMID- 21075197
TI  - D-Isomer of gly-tyr-pro-cys-pro-his-pro peptide: a novel and sensitive in vitro
      trapping agent to detect reactive metabolites by electrospray mass spectrometry.
AB  - This paper describes a D-peptide isomer-based trapping assay using an LC/MS ion
      trap spectrometer with an electrospray ionization (ESI) source as the analytical
      tool to study bioactivation of xenobiotics. Reactive metabolites were generated
      from parent compounds in in vitro incubations with different sources of CYP
      enzymes. A short D-isomer of gly-tyr-pro-cys-pro-his-pro proved to be a sensitive
      trapping agent and resistant to proteases. This method was tested with 16 probe
      substances. Acetaminophen, 1-chloro 2,4-dinitrobenzene, clozapine, diclofenac,
      imipramine, menthofuran, propranolol, pulegone and ticlopidine all formed D
      peptide adducts, which were analogous to the GSH adducts previously described in
      the literature. New adducts were identified with clopidogrel (-Cl+peptide),
      nicotine (-CH(3+)H+peptide), nimesulide (+peptide) and tolcapone (+peptide),
      i.e., no GSH adducts of those drugs have been described in the literature. No
      adducts were identified with ciprofloxacin, ketoconazole and verapamil. In the
      literature no GSH adducts have been described with ciprofloxacin and verapamil. D
      Peptide-based trapping proved to be a reliable and reproducible method to
      identify bioactivated intermediates. D-Peptide is a new and convenient protein
      trapping agent for use in early phase screening of bioactivation of new chemical
      entities and evaluation of toxic properties of chemicals.

PMID- 21075198
TI  - Norcantharidin induces cell cycle arrest and inhibits progression of human
      leukemic Jurkat T cells through mitogen-activated protein kinase-mediated
      regulation of interleukin-2 production.
AB  - Norcantharidin (NCTD) is a potential anti-cancer agent that inhibits
      proliferation and induces cell death through regulation of mitogen-activated
      protein kinases (MAPK). This study examined the effect of NCTD on tumor cells by
      using a model of phorbol 12-myristate 13-acetate plus ionomycin (PMAI)-activated
      leukemia Jurkat T cells. The results showed that NCTD significantly inhibited the
      viability of cells with and without PMAI treatment. NCTD induced cell cycle
      arrest at G2/M phase, down-regulated the expression of calcineurin and, by itself
      or in combination with Cyclosporine A, reduced calcineurin phosphatase activity.
      Furthermore, NCTD up-regulates the expression of phosphorylated (p)-P38 and p
      ERK1/2, but not JNK in PMAI-activated Jurkat T cells, in accordance with the
      alteration in viability. Regarding major cytokine and chemokine secretion
      profile, NCTD attenuates PMAI-augmented production of IL-2, but slightly
      increases or has no effect on TNF-alpha and IL-8. By blockade of various MAPK,
      NCTD regulates PMAI-augmented IL-2 production through activation of P38 and
      ERK1/2, in accordance with the aforementioned MAPK expression. In conclusion,
      NCTD inhibited IL-2 production in PMAI-activated human leukemia Jurkat T cells
      through activation of P38 and ERK1/2, suggesting that NCTD might have the
      potential of being used as a chemopreventive agent to inhibit tumor progression
      in the future.

PMID- 21075200
TI  - Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally
      exposed rats.
AB  - Diisononyl phthalate (DINP) is a plasticizer abundantly used in consumer products
      as a substitute for other plasticizers prohibited in certain products due to
      reproductive toxicity. As anti-androgenic effects of DINP are suspected, DINP
      effects on reproduction and sexually dimorphic behavior were studied. Pregnant
      Wistar rats were gavaged from gestation day 7 to postnatal day (PND) 17 with
      vehicle, 300, 600, 750 or 900 mg DINP/kg bw/day. In fetal testes
      histopathological effects typical of phthalates were observed. In male offspring,
      DINP caused increased nipple retention, reduced anogenital distance, reduced
      sperm motility and increased sperm count. DINP affected spatial learning as
      female offspring performed better than controls and similarly to control males in
      the Morris Water Maze, indicating masculinization of behavior in DINP exposed
      females. These results show that DINP causes anti-androgenic effects on
      reproductive development, though less potent than DEHP, DBP and BBP, and further
      safety evaluation of DINP appears warranted.

PMID- 21075199
TI  - Ascending caudal medullary catecholamine pathways drive sickness-induced deficits
      in exploratory behavior: brain substrates for fatigue?
AB  - Immune challenges can lead to marked behavioral changes, including fatigue,
      reduced social interest, anorexia, and somnolence, but the precise neuronal
      mechanisms that underlie sickness behavior remain elusive. Part of the
      neurocircuitry influencing behavior associated with illness likely includes
      viscerosensory nuclei located in the caudal brainstem, based on findings that
      inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal.
      These brainstem nuclei contribute multiple neuronal projections that target
      different components of autonomic and stress-related neurocircuitry. In
      particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC
      target the hypothalamus and drive neuroendocrine responses to immune challenge,
      but their particular role in sickness behavior is not known. To test whether this
      catecholamine pathway also mediates sickness behavior, we compared effects of DVC
      inactivation with targeted lesion of the catecholamine pathway on exploratory
      behavior, which provides an index of motivation and fatigue, and associated
      patterns of brain activation assessed by immunohistochemical detection of c-Fos
      protein. LPS treatment dramatically reduced exploratory behavior, and produced a
      pattern of increased c-Fos expression in brain regions associated with stress and
      autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the
      stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in
      regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral
      tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and
      catecholamine lesion prevented reductions in exploratory behavior and completely
      blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated
      regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by
      DVC inactivation but not by catecholamine lesion. The findings support the idea
      that parallel pathways from immune-sensory caudal brainstem sources target
      distinct populations of forebrain neurons that likely mediate different aspects
      of sickness. The caudal medullary catecholaminergic projections to the
      hypothalamus may significantly contribute to brain mechanisms that induce
      behavioral "fatigue" in the context of physiological stressors.

PMID- 21075201
TI  - A first insight into the genotypes of Echinococcus granulosus from humans in
      Mongolia.
AB  - Polymerase chain reaction (PCR)-based single-strand conformation polymorphism
      (SSCP) and targeted sequencing were employed to genetically classify Echinococcus
      granulosus cysts from humans from 12 provinces in Mongolia using two DNA loci,
      designated pcox-1 and pnad-1, within the mitochondrial cytochrome c oxidase
      subunit 1 (cox-1) and NADH dehydrogenase subunit 1 (nad-1) genes, respectively.
      SSCP analysis of pcox-1 and pnad-1 amplicons produced from genomic DNA samples
      from individual E. granulosus cysts (n = 50) from individual humans displayed
      four distinct electrophoretic profiles for each pcox-1 and pnad-1. The direct
      sequencing of selected amplicons representing each of these profiles defined four
      distinct sequence types for each locus, present in four different combinations
      (designated as haplotypes M1-M4) for all 50 cyst isolates. Phylogenetic analysis
      of concatenated sequence data for these four haplotypes, including well-defined
      reference sequences, inferred that 68% of the cyst isolates belonged to the G1-G3
      complex of E. granulosus (or E. granulosus sensu stricto), whereas the remaining
      (32%) were linked to the G6-G10 complex (or Echinococcus canadensis). Humans
      infected with E. granulosus cysts of the G1-G3 complex originated mainly from the
      eastern regions of Mongolia, whereas those harbouring cysts of the G6-G10 complex
      were from the western part of this country. The present study provides a first
      glimpse of the genetic composition of E. granulosus from humans in Mongolia, and
      forms a foundation for future studies of the epidemiology and ecology of the
      parasite(s) in animals and humans in this and surrounding countries.

PMID- 21075202
TI  - Reference ranges of urinary biomarkers of oxidized guanine in (2'
      deoxy)ribonucleotides and nucleic acids.
AB  - This study was aimed at defining the reference ranges for biomarkers of oxidized
      guanine in (2'-deoxy)ribonucleotides and nucleic acids from a large Italian
      sample. We recruited 300 healthy subjects (150 males; mean age 44.1+/-13.6years;
      26% smokers) without any known exposure to occupational oxidizing agents. They
      were asked to provide a spot urine sample, on which the following markers were
      determined by liquid chromatography-tandem mass spectrometry: 8-oxo-7,8-dihydro
      2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), 8-oxo-7,8
      dihydroguanine (8-oxoGua), and cotinine. The reference ranges, estimated as the
      5th-95th percentiles of creatinine-normalized values (pmol/MUmol(creat)) were 0.7
      4.2, 0.9-4.7, and 5.6-120.7 for 8-oxodGuo, 8-oxoGuo, and 8-oxoGua, respectively.
      Oxidation biomarkers were correlated with one another (p<0.005) and with urinary
      creatinine (p<0.0001). Males excreted significantly higher concentrations of 8
      oxoGua than females (p<0.0001). 8-OxoGua and 8-oxoGuo showed a positive
      association with age (p<0.001), also after stratification by gender. Multiple
      linear regression models including urinary creatinine concentration, age, and
      smoking habit as independent variables showed a significant effect of age, but
      not of smoking, on the levels of 8-oxoGuo in males (p<0.0001) and of both 8
      oxoGuo and 8-oxoGua in females (p<0.0001). A preliminary assessment in a small
      group (n=25) of patients affected by advanced non-small-cell lung cancer and
      receiving platinum-based chemotherapy showed significantly higher values of both
      8-oxoGuo and 8-oxodGuo (p<0.0001 for both) compared to the referent population.

PMID- 21075203
TI  - Oxidatively generated DNA damage after Cu(II) catalysis of dopamine and related
      catecholamine neurotransmitters and neurotoxins: Role of reactive oxygen species.
AB  - There is increasing evidence supporting a causal role for oxidatively damaged DNA
      in neurodegeneration during the natural aging process and in neurodegenerative
      diseases such as Parkinson and Alzheimer. The presence of redox-active
      catecholamine neurotransmitters coupled with the localization of catalytic copper
      to DNA suggests a plausible role for these agents in the induction of oxidatively
      generated DNA damage. In this study we have investigated the role of Cu(II)
      catalyzed oxidation of several catecholamine neurotransmitters and related
      neurotoxins in inducing oxidatively generated DNA damage. Autoxidation of all
      catechol neurotransmitters and related congeners tested resulted in the formation
      of nearly a dozen oxidation DNA products resulting in a decomposition pattern
      that was essentially identical for all agents tested. The presence of Cu(II), and
      to a lesser extent Fe(III), had no effect on the decomposition pattern but
      substantially enhanced the DNA product levels by up to 75-fold, with dopamine
      producing the highest levels of unidentified oxidation DNA products (383+/-46
      adducts/10(6) nucleotides), nearly 3-fold greater than 8-oxo-7,8-dihydro-2'
      deoxyguanosine (122+/-19 adducts/10(6) nucleotides) under the same conditions.
      The addition of sodium azide, 2,2,6,6-tetramethyl-4-piperidone, tiron, catalase,
      bathocuproine, or methional to the dopamine/Cu(II) reaction mixture resulted in a
      substantial decrease (>90%) in oxidation DNA product levels, indicating a role
      for singlet oxygen, superoxide, H(2)O(2), Cu(I), and Cu(I)OOH in their formation.
      Whereas the addition of N-tert-butyl-alpha-phenylnitrone significantly decreased
      (67%) dopamine-mediated oxidatively damaged DNA, three other hydroxyl radical
      scavengers, ascorbic acid, sodium benzoate, and mannitol, had little to no effect
      on these oxidation DNA product levels, suggesting that free hydroxyl radicals may
      have limited involvement in this dopamine/Cu(II)-mediated oxidatively generated
      DNA damage. These studies suggest a possible contributory role of oxidatively
      generated DNA damage by dopamine and related catechol
      neurotransmitters/neurotoxins in neurodegeneration and cell death. We also found
      that a naturally occurring broad-spectrum antioxidant, ellagic acid, was
      substantially effective (nearly 50% inhibition) at low doses (1MUM) at preventing
      this dopamine/Cu(II)-mediated oxidatively generated DNA damage. Because dietary
      ellagic acid has been found to reduce oxidative stress in rat brains, a
      neuroprotective role of this polyphenol is plausible.

PMID- 21075204
TI  - The biological significance of methionine sulfoxide stereochemistry.
AB  - Methionine can be oxidized by reactive oxygen species to a mixture of two
      diastereomers, methionine-S-sulfoxide and methionine-R-sulfoxide. Both free amino
      acid and protein-based forms of methionine-S-sulfoxide are stereospecifically
      reduced by MsrA, whereas the reduction of methionine-R-sulfoxide requires two
      enzymes, MsrB and fRMsr, which act on its protein-based and free amino acid
      forms, respectively. However, mammals lack fRMsr and are characterized by
      deficiency in the reduction of free methionine-R-sulfoxide. The biological
      significance of such biased reduction of methionine sulfoxide has not been fully
      explored. MsrA and MsrB activities decrease during aging, leading to accumulation
      of protein-based and free amino acid forms of methionine sulfoxide. Since
      methionine is an indispensible amino acid in human nutrition and a key metabolite
      in sulfur, methylation, and transsulfuration pathways, the consequences of
      accumulation of its oxidized forms require further studies. Finally, in addition
      to methionine, methylsulfinyl groups are present in various drugs and natural
      compounds, and their differential reduction by Msrs may have important
      therapeutic implications.

PMID- 21075205
TI  - Autodisplay of catalytically active human hyaluronidase hPH-20 and testing of
      enzyme inhibitors.
AB  - Hyaluronic acid (HA) is the major biopolymer of the extracellular matrix and
      contributes significantly to cell proliferation and migration. Human
      hyaluronidase hPH-20 has been identified as a tumor marker for breast and
      laryngeal cancer. A hPH-20-autotransporter fusion protein for cell surface
      display was transformed into Escherichia coli BL21 (DE3) and hPH-20 was displayed
      on the surface of E. coli. Enzymatic activity, however, was not detectable due to
      competitive inhibition by lipopolysaccharide (LPS). Finally, expression in E.
      coli F470, a strain missing the O-polysaccharide of LPS, yielded cells with
      sufficient hyaluronidase activity. 6-Palmitoyl-l-ascorbic acid (Vcpal) and two
      indole-carboxamides, N-(4-fluorobenzyl)-1-benzyl-1H-indole-2-carboxamide (1) and
      N-(4-chlorobenzyl)-1-(4-fluorobenzyl)-1H-indole-3-carboxamide (2), were tested on
      inhibition of hPH-20. Vcpal with a concentration of 5 MUM inhibited hPH-20 to 93%
      at pH 7, compounds 1 and 2 showed 61% and 21% inhibition at a concentration of 50
      MUM. At the same inhibitor concentrations the most frequently used bovine testes
      hyaluronidase (BTH) was inhibited by Vcpal to a similar extent (95%), whereas
      compound 1 (80%) and compound 2 (66%) showed much differing inhibition. Thus it
      can be assumed that BTH is not applicable as an alternative to human PH-20. These
      results indicate that Autodisplay enables the expression of human target enzymes
      normally forming inclusion bodies in E. coli and accelerates inhibitor testing as
      shown by the example of human hyaluronidase PH-20.

PMID- 21075206
TI  - Polymer conjugates of the highly potent cytostatic drug 2-pyrrolinodoxorubicin.
AB  - This paper describes the synthesis and biological evaluation of a conjugate of
      the highly cytotoxic drug 2-pyrrolinodoxorubicin (p-DOX) with an N-(2
      hydroxypropyl)methacrylamide copolymer (PHPMA) as a water-soluble biocompatible
      polymer carrier, utilizing the advantageous concept of polymer-drug conjugates.
      The conjugate of p-DOX with HPMA copolymer (PHPMA/p-DOX) was prepared by reacting
      the PHPMA/DOX conjugate, where the DOX was bound via a hydrazone bond, with 4
      iodobutyraldehyde. The hydrazone bond between the polymer and drug is susceptible
      to pH-controlled hydrolysis, enabling prolonged stability in circulation and fast
      p-DOX release under conditions mimicking the intracellular environment. The in
      vitro cytostatic activity of free p-DOX was in accordance with literature,
      whereas its PHPMA conjugate exhibited a 1.3- to 5-fold lower cytotoxicity,
      depending on the cancer cell line, when compared to the free p-DOX. This is in
      qualitative agreement with the data obtained for DOX and its HPMA copolymer
      conjugates. On mice bearing T-cell EL4 lymphoma, no tumor suppression was
      observed from the free p-DOX at a subtoxic dose of 0.1 mg/kg, whereas the PHPMA/p
      DOX conjugate significantly inhibited the initial tumor growth at approximately
      equitoxic doses of 0.4 and 0.8 mg p-DOX eq/kg. However, moderately elevated doses
      of the p-DOX equivalent in the conjugate caused toxic effects, making accurate
      dosage setting essential.

PMID- 21075207
TI  - Exploring functional relations between brain regions from fMRI meta-analysis
      data: comments on Ramsey, Spirtes, and Glymour.
AB  - In this paper, we address the critical assessment of Ramsey et al. of our method
      for learning partially directed graphs from meta-analysis imaging data (Neumann
      et al., 2010). We argue that our method provides valid and interpretable results
      when applied to data representing a single experimental paradigm. Simulations
      further suggest that, despite theoretical limitations, the application of our
      method to mixed probability distributions yields reliable results with error
      rates at acceptable levels. Finally, we discuss the nature of meta-analysis data
      and the notion of causality in the context of functional neuroimaging.

PMID- 21075208
TI  - Phylogenetic relationships among insect orders based on three nuclear protein
      coding gene sequences.
AB  - Many attempts to resolve the phylogenetic relationships of higher groups of
      insects have been made based on both morphological and molecular evidence;
      nonetheless, most of the interordinal relationships of insects remain unclear or
      are controversial. As a new approach, in this study we sequenced three nuclear
      genes encoding the catalytic subunit of DNA polymerase delta and the two largest
      subunits of RNA polymerase II from all insect orders. The predicted amino acid
      sequences (In total, approx. 3500 amino acid sites) of these proteins were
      subjected to phylogenetic analyses based on the maximum likelihood and Bayesian
      analysis methods with various models. The resulting trees strongly support the
      monophyly of Palaeoptera, Neoptera, Polyneoptera, and Holometabola, while within
      Polyneoptera, the groupings of Isoptera/"Blattaria"/Mantodea (Superorder
      Dictyoptera), Dictyoptera/Zoraptera, Dermaptera/Plecoptera,
      Mantophasmatodea/Grylloblattodea, and Embioptera/Phasmatodea are supported.
      Although Paraneoptera is not supported as a monophyletic group, the grouping of
      Phthiraptera/Psocoptera is robustly supported. The interordinal relationships
      within Holometabola are well resolved and strongly supported that the order
      Hymenoptera is the sister lineage to all other holometabolous insects. The other
      orders of Holometabola are separated into two large groups, and the interordinal
      relationships of each group are (((Siphonaptera, Mecoptera), Diptera),
      (Trichoptera, Lepidoptera)) and ((Coleoptera, Strepsiptera), (Neuroptera,
      Raphidioptera, Megaloptera)). The sister relationship between Strepsiptera and
      Diptera are significantly rejected by all the statistical tests (AU, KH and wSH),
      while the affinity between Hymenoptera and Mecopterida are significantly rejected
      only by AU and KH tests. Our results show that the use of amino acid sequences of
      these three nuclear genes is an effective approach for resolving the
      relationships of higher groups of insects.

PMID- 21075209
TI  - Are subspecies of Anolis lizards that differ in dewlap color and pattern also
      genetically distinct? A mitochondrial analysis.
AB  - Subspecies of Anolis lizards are often defined on the basis of geographic
      variation in the color and pattern of the dewlap, an extensible throat fan
      considered central to species recognition and sexual selection. Among the most
      impressive examples of this phenomenon are two species of trunk anoles found
      across Hispaniola and the Bahamas: Anolis distichus is divided into 16 subspecies
      with dewlap colors ranging from deep wine red to pale yellow while Anolis
      brevirostris is divided into three subspecies with dewlaps ranging from pale
      yellow to orange. Limited sampling of allozyme data indicates some genetic
      divergence among subspecies and suggests that they may deserve recognition at the
      species-level. Our goal here is to use more comprehensive geographic sampling of
      mtDNA haplotypes to test whether the five subspecies of A. distichus and three
      subspecies of A. brevirostris that occur in the Dominican Republic correspond
      with genetically distinct populations that may warrant recognition under the
      general lineage concept. We obtain an aligned dataset of 1462bp comprised of the
      genes encoding ND2 and adjacent tRNAs from 76 individuals of A. distichus from 28
      localities and 12 individuals of A. brevirostris from five localities. We find
      that haplotypes sampled from each Dominican subspecies of A. distichus form well
      supported and deeply divergent clades (>10% uncorrected sequence divergence).
      Strong concordance between mtDNA haplotype structure and previously diagnosed
      phenotypic variation in traits central to interspecific communication (i.e., the
      dewlap) leads us to hypothesize that each of the presently recognized Dominican
      subspecies of A. distichus and A. brevirostris deserves elevation to full species
      status under the general lineage concept.

PMID- 21075210
TI  - Involvement of the CLEC3B gene in osteoarthritis.

PMID- 21075211
TI  - Reducing the allowable kinetic space by constructing ensemble of dynamic models
      with the same steady-state flux.
AB  - Dynamic models of metabolism are instrumental for gaining insight and predicting
      possible outcomes of perturbations. Current approaches start from the selection
      of lumped enzyme kinetics and determine the parameters within a large parametric
      space. However, kinetic parameters are often unknown and obtaining these
      parameters requires detailed characterization of enzyme kinetics. In many cases,
      only steady-state fluxes are measured or estimated, but these data have not been
      utilized to construct dynamic models. Here, we extend the previously developed
      Ensemble Modeling methodology by allowing various kinetic rate expressions and
      employing a more efficient solution method for steady states. We show that
      anchoring the dynamic models to the same flux reduces the allowable parameter
      space significantly such that sampling of high dimensional kinetic parameters
      becomes meaningful. The methodology enables examination of the properties of the
      model's structure, including multiple steady states. Screening of models based on
      limited steady-state fluxes or metabolite profiles reduces the parameter space
      further and the remaining models become increasingly predictive. We use both
      succinate overproduction and central carbon metabolism in Escherichia coli as
      examples to demonstrate these results.

PMID- 21075212
TI  - A CRE that binds CREB and contributes to PKA-dependent regulation of the proximal
      promoter of human RAB25 gene.
AB  - RAB25 plays an important role in tumor progression and aggressiveness; altered
      RAB25 expression may cause human cancer. As the underlying mechanism of RAB25
      mediated carcinogenesis in various tumor types progressively comes to light,
      RAB25 is expected to represent a novel therapeutic target. However, the
      regulation of RAB25 expression per se has not yet been described. Here we have
      firstly identified and characterized the human RAB25 promoter. Using PCR-based
      chromatin accessibility and chromatin immunoprecipitation (ChIP) assays, an open
      chromatin conformation (-173/+17) was detected around the transcription start
      site of the RAB25 gene. Deletion constructs of the 5' flanking region were fused
      to a luciferase reporter gene. After transient transfection in gastric cancer
      cell line AGS, a CRE (-67/-58) binding CREB was identified in the core promoter
      region. Electrophoretic mobility shift (EMSA) and ChIP assays demonstrated that
      CREB binds to the core promoter. Deletion of CREB consensus sequence resulted in
      the total loss of the promoter activity. Moreover, we have also found forskolin,
      PKA activator, could enhance open chromatin accessibility, by which to expose the
      CRE and facilitate phosphorylation of CREB, which in turn recruits co-factor CBP
      and Brg I and then results in a more open chromatin configuration associated with
      local histone modification, finally heightening RAB25 expression and
      strengthening its promoter activity. Therefore, the present study delineates the
      fundamental elements of a core promoter structure that will be helpful for future
      studies regarding the regulation of RAB25 gene.

PMID- 21075213
TI  - Vitellogenin, a multivalent sensor and an antimicrobial effector.
AB  - Vitellogenin (Vg), the precursor of yolk proteins, was traditionally regarded as
      the energy reserve for nourishment of the developing embryos. However, its roles
      to extend beyond the nutrient function. Here we discuss recent developments in
      the understanding of Vg. Accumulating data have demonstrated that Vg fulfils
      important roles in innate immune responses. It acts as a multivalent pattern
      recognition receptor capable of binding to lipopolysaccharide, lipoteichoic acid,
      peptidolycan, glucan and virons. It is also a bactericidal molecule capable of
      damaging bacterial cell walls. Moreover, it is an acute phase protein with
      bacterial-binding and inhibiting activities, and possibly functions in the immune
      responses of host in vivo. Further understanding of Vg and its derived yolk
      proteins should provide new insights into the mechanisms of host defense, and
      reveal if they can be used as alternative strategies promoting the immunity of
      cultured fish as well as developing embryos.

PMID- 21075214
TI  - A critical role for the protein phosphatase 2A B'alpha regulatory subunit in
      dephosphorylation of sphingosine kinase 1.
AB  - Sphingosine kinase 1 (SK1) is an important regulator of cellular signalling that
      has gained recent attention as a potential target for anti-cancer therapies. SK1
      activity, subcellular localization and oncogenic function are regulated by
      phosphorylation and dephosphorylation at Ser225. ERK1/2 have been identified as
      the protein kinases responsible for phosphorylation and activation of SK1.
      Conversely, dephosphorylation and deactivation of SK1 occurs by protein
      phosphatase 2A (PP2A). Active PP2A, however, is a heterotrimer, composed of
      tightly associated catalytic and structural subunits that can interact with an
      array of regulatory subunits, which are critical for determining holoenzyme
      substrate specificity and subcellular localization. Thus, PP2A represents a large
      family of holoenzyme complexes with different activities and diverse substrate
      specificities. To date the regulatory subunit essential for targeting PP2A to SK1
      has remained undefined. Here, we demonstrate a critical role for the B'alpha
      (B56alpha/PR61alpha/PPP2R5A) regulatory subunit of PP2A in SK1 dephosphorylation.
      B'alpha was found to interact with the c-terminus of SK1, and reduce SK1
      phosphorylation when overexpressed, while having no effect on upstream ERK1/2
      activation. siRNA-mediated knockdown of B'alpha increased SK1 phosphorylation,
      activity and membrane localization of endogenous SK1. Furthermore, overexpression
      of B'alpha blocked agonist-induced translocation of SK1 to the plasma membrane
      and abrogated SK1-induced neoplastic transformation of NIH3T3 fibroblasts. Thus,
      the PP2A-B'alpha holoenzyme appears to function as an important endogenous
      regulator of SK1.

PMID- 21075215
TI  - Differential genetic responses to ionizing irradiation in individual families of
      Japanese medaka, Oryzias latipes.
AB  - Although no statistically significant hereditary effects have yet been detected
      in the children of survivors from the atomic bombings in Hiroshima and Nagasaki,
      recent animal studies have found that exposure to ionizing radiation can cause
      genomic and epigenomic instability in the exposed individuals, as well as their
      offspring, and therefore, may have much larger genetic effects than predicted by
      earlier studies. When individuals are exposed to various environmental insults,
      including radiation, individual sensitivity to the insults often varies. Variance
      in germ-line response to radiation among individuals has been widely recognized,
      but it is difficult to address due to the use of inbred strains and the limited
      number of offspring that can be produced by a pair of mice, the common model used
      to study genetic effects of radiation. Herein is the first study to examine
      individual family responses to ionizing radiation using a parent-pedigree
      approach in an outbred strain of a vertebrate model, the Japanese medaka fish.
      Changes in frequencies of radiation-induced germline mutations at nine
      microsatellite loci were examined in the same families before and after exposure
      to one of four acute doses of ionizing radiation (0.1, 0.5, 2.5, 5Gy, plus sham
      exposed controls). Families varied significantly in pre-exposure mutation
      frequencies and responses to irradiation, but germline mutations were elevated in
      at least one family after 0.1, 0.5, and 5Gy exposures. Variance among individuals
      in sensitivity to radiation is well documented for many endpoints, and our work
      now extends these endpoints to include germ-line mutations. Further studies are
      needed to elucidate dose response, effects at varying stages of spermatogenesis,
      and the mechanisms underlying the variance in these individual responses to
      radiation.

PMID- 21075216
TI  - Morphologic pattern of the intrinsic ganglionated nerve plexus in mouse heart.
AB  - BACKGROUND: Both normal and genetically modified mice are excellent models for
      investigating molecular mechanisms of arrhythmogenic cardiac diseases that may be
      associated with an imbalance between sympathetic and parasympathetic nervous
      input to the heart. OBJECTIVE: The purpose of this study was to (1) determine the
      structural organization of the mouse cardiac neural plexus, (2) identify
      extrinsic neural sources and their relationship with the cardiac plexus, and (3)
      reveal any anatomic differences in the cardiac plexus between mouse and other
      species. METHODS: Cardiac nerve structures were visualized using histochemical
      staining for acetylcholinesterase (AChE) on whole heart and thorax-dissected
      preparations derived from 25 mice. To confirm the reliability of staining
      parasympathetic and sympathetic neural components in the mouse heart, we applied
      a histochemical method for AChE and immunohistochemistry for tyrosine hydroxylase
      (TH) and/or choline acetyltransferase (ChAT) on whole mounts preparations from
      six mice. RESULTS: Double immunohistochemical labeling of TH and ChAT on AChE
      positive neural elements in mouse whole mounts demonstrated equal staining of
      nerves and ganglia for AChE that were positive for both TH and ChAT. The
      extrinsic cardiac nerves access the mouse heart at the right and left cranial
      veins and interblend within the ganglionated nerve plexus of the heart hilum that
      is persistently localized on the heart base. Nerves and bundles of nerve fibers
      extend epicardially from this plexus to atria and ventricles by left dorsal,
      dorsal right atrial, right ventral, and ventral left atrial routes or
      subplexuses. The right cranial vein receives extrinsic nerves that mainly
      originate from the right cervicothoracic ganglion and a branch of the right vagus
      nerve, whereas the left cranial vein is supplied by extrinsic nerves from the
      left cervicothoracic ganglion and the left vagus nerve. The majority of intrinsic
      cardiac ganglia are localized on the heart base at the roots of the pulmonary
      veins. These ganglia are interlinked by interganglionic nerves into the above
      mentioned nerve plexus of the heart hilum. In general, the examined hearts
      contained 19 +/- 3 ganglia, giving a cumulative ganglion area of 0.4 +/- 0.1
      mm(2). CONCLUSION: Despite substantial anatomic differences in ganglion number
      and distribution, the structural organization of the intrinsic ganglionated
      plexus in the mouse heart corresponds in general to that of other mammalian
      species, including human.

PMID- 21075217
TI  - Deconstructing complex fractionated atrial electrograms: just how complex and
      fractionated are they?

PMID- 21075218
TI  - Mechanoelectrical coupling enhances initiation and affects perpetuation of atrial
      fibrillation during acute atrial dilation.
AB  - BACKGROUND: Acute atrial dilation increases the susceptibility to atrial
      fibrillation (AF). However, the mechanisms by which atrial stretch may contribute
      to the initiation and perpetuation of AF remain to be determined. OBJECTIVE: The
      purpose of this study was to use a novel multiscale model of atrial
      electromechanics and mechanoelectrical feedback to test the hypothesis that acute
      stretch increases vulnerability to AF by heterogeneous activation of stretch
      activated channels. METHODS: Human atria were represented by a triangular mesh
      obtained from magnetic resonance imaging data. Atrial trabecular bundle structure
      was incorporated by varying thicknesses of the atrial wall. Atrial membrane
      behavior was modeled by the Courtemanche-Ramirez-Nattel model with the addition
      of a nonselective stretch-activated cation current (I(sac)). Mechanical behavior
      was modeled by a series elastic, a contractile, and a parallel elastic element in
      which contractile force was related to intracellular concentration of free
      calcium and sarcomere length. RESULTS: Acute atrial dilation was simulated by
      increasing stretch throughout the atrial wall. Stimulation near the pulmonary
      vein ostia at an interval of 600 ms induced AF at an overall stretch ratio of
      1.10. Initiation and perpetuation of AF in our model were related to increased
      dispersion of effective refractory period, conduction slowing, and local
      conduction block, all related to heterogeneous activation of I(sac). Upon local
      contraction, mechanoelectrical coupling affects perpetuation of AF by temporarily
      changing local excitability. CONCLUSION: During acute atrial dilation,
      heterogeneous activation of I(sac) enhances initiation and can affect
      perpetuation of AF.

PMID- 21075219
TI  - Strong genetic structure in Cameroonian populations of Bulinus truncatus
      (Gastropoda: Planorbidae), intermediate host of Schistosoma haematobium.
AB  - In order to evaluate the snail host contribution on the variability of
      mollusk/schistosome compatibility, the genetic structure of seven Cameroonian
      populations of the schistosome vector, Bulinus truncatus, was studied using four
      variable microsatellite loci. A substantial polymorphism mainly distributed among
      populations was observed. No heterozygous genotype was scored, confirming the
      high level of selfing rate occurring in B. truncatus populations. Contemporaneous
      samples were highly and significantly differentiated with a marginally
      significant correlation with geographical distances (P-value=0.069). The
      different sites sampled seemed to rarely exchange migrants with very small Nm
      (~0.22 or below). The data also suggest that B. truncatus subpopulations might be
      composed of very small and isolated units at much smaller surfaces than what was
      investigated. Even if more data (in particular more loci) will be needed to
      confirm these issues, they suggest that restricted gene flow plays an important
      role in maintaining differentiation among snail populations in the transmission
      foci, potentially leading to specific adaptation between each B. truncatus
      population and its local Schistosoma haematobium population.

PMID- 21075220
TI  - Three fatal cases of pandemic 2009 influenza A virus infection in Shenzhen are
      associated with cytokine storm.
AB  - China had taken strict measures for pandemic 2009 H1N1 infection with enhanced
      surveillance and hospital isolation since April 2009. In Shenzhen, over 1200
      confirmed cases of H1N1 infection were identified. Three young patients died of
      severe pneumonia. Among them, two boys developed neurological complications.
      Cytokine storm seemed an important cause.

PMID- 21075221
TI  - Anodic mesoporous TiO2 layer on Ti for enhanced formation of biomimetic
      hydroxyapatite.
AB  - Ti surfaces can be very efficiently coated by a robust (MUm thick) mesoporous
      titania layer (MTL). These coatings are produced by anodization of Ti at elevated
      temperature in a glycerol/K(2)HPO(4) electrolyte, followed by an appropriate
      etching process. In the present work we examine these layers with regard to their
      ability to form hydroxyapatite. Immersion tests in two types of simulated body
      fluids (Kokubo SBF and Bohner and Lemaitre SBF) combined with scanning electron
      microscopy, X-ray diffraction and X-ray photoelectron spectroscopy investigations
      show that these MTL layers lead to a significant enhancement of HAp formation and
      anchoring in the structure compared with non-coated or even nanotubular Ti
      surface coatings (these were recently reported to be the most efficient in terms
      of HAp formation).

PMID- 21075222
TI  - A multidisciplinary approach to post-bariatric plastic surgery.
AB  - Social changes over the last 100 years, but predominantly since the invention of
      'fast food' have led to an explosion in obesity. The National Institute for
      Clinical Excellence advise referral of patients with body mass indices >40 for
      bariatric surgery. One third of post-bariatric surgery patients achieve massive
      weight loss necessitating reconstructive body contour surgery. This unique group
      of patients presents multiple challenges for medical and ancillary practitioners
      involved in their care. A multidisciplinary approach is essential.

PMID- 21075223
TI  - Improvement of a phiC31 integrase-based gene delivery system that confers high
      and continuous transgene expression.
AB  - phiC31 integrase-based gene delivery has been developed. However, the expression
      of integrated transgenes is often suppressed by a negative position effect. To
      improve this system, we constructed a new phiC31 integrase-based expression
      vector that contains attB, an expression unit placed in reverse orientation with
      two sea urchin-derived Ars-insulators to avoid position effects. In vitro and in
      vivo transfection experiments revealed that this new system produces higher
      levels of transgene expression as well as continued gene expression. Thus, the
      present gene delivery system will facilitate reverse genetics-based molecular
      biological studies.

PMID- 21075224
TI  - Generation of B. nigra-B. rapa chromosome addition stocks: cytology and
      microsatellite markers (SSRs) based characterization.
AB  - To improve Brassica nigra, the B-genome donor for Brassica juncea through
      selective introgression of useful variation from A-genome chromosomes, B. nigra
      B. rapa chromosome addition stocks were successfully synthesized for the first
      time. Resynthesized B. juncea was used as B-genome donor species and A-genome
      addition stocks were developed by hybridizing sesquidiploid plant (ABB) as female
      and using B. nigra as the male parent. Various cycles of backcrossing and/or
      selfing were utilized to isolate plants carrying addition of three A-genome
      chromosomes in the background of B. nigra. These chromosome addition stocks were
      characterized by chromosome counts, pollen and seed fertility and chromosome
      specific microsatellite (SSRs) markers. The chromosome number in different
      backcross/self generations ranged between 2n=26 and 2n=19 with relatively high
      frequency of univalents (8-10I) at in meiotic configurations observed, suggesting
      the role of preferential transmission of A-genome chromosomes. SSRs analysis
      revealed that B. rapa chromosomes 3 and 4 were the first to get eliminated
      followed by chromosome 10. Remaining chromosomes were maintained till BC(1)F(4).
      However, second cycle of backcrossing (BC(2)) led to the elimination of
      chromosome numbers 1 and 2. BC(2)F(2) plants carried the chromosome numbers 6, 7,
      8 and 9. Generation BC(3) having plants with 2n=19 carried chromosome numbers 6,
      7 and 8. It is possible that chromosomes 6, 7 and 8 had higher transmission
      frequency and these were better tolerated by the B. nigra genome.

PMID- 21075225
TI  - Untangling the intracellular signalling network in cancer--a strategy for data
      integration in acute myeloid leukaemia.
AB  - Protein and gene networks centred on the regulatory tumour suppressor proteins
      may be of crucial importance both in carcinogenesis and in the response to
      chemotherapy. Tumour suppressor protein p53 integrates intracellular data in
      stress responses, receiving signals and translating these into differential gene
      expression. Interpretation of the data integrated on p53 may therefore reveal the
      response to therapy in cancer. Proteomics offers more specific data - closer to
      "the real action" - than the hitherto more frequently used gene expression
      profiling. Integrated data analysis may reveal pathways disrupted at several
      regulatory levels. Ultimately, integrated data analysis may also contribute to
      finding key underlying cancer genes. We here proposes a Partial Least Squares
      Regression (PLSR)-based data integration strategy, which allows simultaneous
      analysis of proteomic data, gene expression data and classical clinical
      parameters. PLSR collapses multidimensional data into fewer relevant dimensions
      for data interpretation. PLSR can also aid identification of functionally
      important modules by also performing comparison to databases on known biological
      interactions. Further, PLSR allows meaningful visualization of complex datasets,
      aiding interpretation of the underlying biology. Extracting the true biological
      causal mechanisms from heterogeneous patient populations is the key to discovery
      of new therapeutic options in cancer.

PMID- 21075226
TI  - Attention bias modification training and the new interventions research.

PMID- 21075227
TI  - An odyssey of fear: Homer stresses new mechanisms.

PMID- 21075228
TI  - Metabotropic glutamate receptor 5/Homer interactions underlie stress effects on
      fear.
AB  - BACKGROUND: Glutamatergic transmission is one of the main components of the
      stress response; nevertheless, its role in the emotional stress sequelae is not
      known. Here, we investigated whether interactions between group I metabotropic
      glutamate receptors (metabotropic glutamate receptor 1 and metabotropic glutamate
      receptor 5 [mGluR5]) and Homer proteins mediate the delayed and persistent
      enhancement of fear induced by acute stress. METHODS: Antagonists and inverse
      agonists of metabotropic glutamate receptor 1 and mGluR5 were injected into the
      hippocampus after immobilization stress and before contextual fear conditioning.
      Metabotropic glutamate receptor 5 was displaced from constitutive Homer scaffolds
      by viral transfection of Homer1a or injection of Tat decoy peptides. The effects
      of these manipulations on stress-enhanced fear were determined. RESULTS: We show
      that stress induces interactions between hippocampal mGluR5 and Homer1a; causes a
      sustained, ligand-independent mGluR5 activity; and enhances contextual fear.
      Consistent with this mechanism, enhancement of fear was abolished by delayed
      poststress application of inverse agonists, but not antagonists, of mGluR5. The
      effect of stress was mimicked by virally transfected Homer1a or injection of Tat
      metabotropic glutamate receptor C-tail decoy peptides into the hippocampus.
      CONCLUSIONS: Constitutive activation of mGluR5 is identified as a principal
      hippocampal mechanism underlying the delayed stress effects on emotion and
      memory. Inverse agonists, but not antagonists, of mGluR5 are therefore proposed
      as a preventive treatment option for acute and posttraumatic stress disorders.

PMID- 21075229
TI  - Prefrontal mechanisms of fear reduction after threat offset.
AB  - INTRODUCTION: Reducing fear when a threat has disappeared protects against a
      continuously elevated anxiety state. In this study, we investigated the brain
      mechanism involved in this process. METHODS: The threat paradigm consisted of
      discrete cues that signaled either threat of shock or safety. Healthy
      participants were tested in two sessions in which eyeblink startle (n = 26) and
      blood oxygen level dependence (n = 23) were measured to index subjects' defensive
      state and brain responses respectively. RESULTS: Startle results indicated that
      subjects could rapidly decrease their defensive state after the offset of shock
      threat. Functional magnetic resonance imaging data indicated that the termination
      of threat was associated with the recruitment of lateral and ventromedial
      prefrontal cortices. An exploratory connectivity analysis showed that activity in
      these prefrontal regions was linked and was also associated with activity in
      brain regions typically responding to threat, the right anterior insula and
      amygdala. CONCLUSIONS: These results provide first evidence for a prefrontal
      mechanism that functions to control anxiety after threat offset, which may be
      dysfunctional in patients who suffer from excessive sustained anxiety. Moreover,
      the results support a model in which the lateral prefrontal cortex controls
      anxiety related limbic activity through connections with ventromedial prefrontal
      cortex.

PMID- 21075231
TI  - Measurement of sleep.
AB  - Rapid eye movement (REM) and non-REM sleep processes affect the electrical
      signals from brain, eyes and muscles. Recording these signals during sleep
      imposes special demands on electrodes, technicians and equipment. Both human and
      computerized signal analysis can then be applied to quantify the sleep processes.
      The most practical and state-of-the-art recording and analysis methods are
      discussed with emphasis on the most important details. Other analysis methods can
      be judged based on a few simple criteria.

PMID- 21075232
TI  - Measurement of cognition in studies of sleep deprivation.
AB  - Controlled laboratory studies of the effects of sleep deprivation on cognition
      have the potential to further our understanding of why some complex tasks are
      more affected by lack of sleep than other tasks. However, apparently simple
      cognitive tasks reflect multiple cognitive processes at once. Some of the
      component processes involved in a task may be more affected by sleep deprivation
      than others. Thus, interpreting measures of overall performance without
      consideration of the specific task requirements can lead to misleading
      conclusions. Using examples from studies of attention, working memory and
      executive functioning, we demonstrate the importance of analysing how different
      task components contribute to performance and how the nature of the stimulus
      content can influence outcomes of sleep deprivation studies. Recent developments
      in cognitive neuropsychology may help sleep researchers conduct more precise
      tests of fatigue effects on cognition. In turn, studies of sleep and cognition
      hold promise as a strategy for the development of better general models of how
      the cognitive system adjusts dynamically to impairments in processing.

PMID- 21075230
TI  - Cognitive neuroscience of sleep.
AB  - Mechanism is at the heart of understanding, and this chapter addresses underlying
      brain mechanisms and pathways of cognition and the impact of sleep on these
      processes, especially those serving learning and memory. This chapter reviews the
      current understanding of the relationship between sleep/waking states and
      cognition from the perspective afforded by basic neurophysiological
      investigations. The extensive overlap between sleep mechanisms and the
      neurophysiology of learning and memory processes provide a foundation for
      theories of a functional link between the sleep and learning systems. Each of the
      sleep states, with its attendant alterations in neurophysiology, is associated
      with facilitation of important functional learning and memory processes. For
      rapid eye movement (REM) sleep, salient features such as PGO waves, theta
      synchrony, increased acetylcholine, reduced levels of monoamines and, within the
      neuron, increased transcription of plasticity-related genes, cumulatively allow
      for freely occurring bidirectional plasticity, long-term potentiation (LTP) and
      its reversal, depotentiation. Thus, REM sleep provides a novel neural environment
      in which the synaptic remodelling essential to learning and cognition can occur,
      at least within the hippocampal complex. During non-REM sleep Stage 2 spindles,
      the cessation and subsequent strong bursting of noradrenergic cells and
      coincident reactivation of hippocampal and cortical targets would also increase
      synaptic plasticity, allowing targeted bidirectional plasticity in the neocortex
      as well. In delta non-REM sleep, orderly neuronal reactivation events in phase
      with slow wave delta activity, together with high protein synthesis levels, would
      facilitate the events that convert early LTP to long-lasting LTP. Conversely,
      delta sleep does not activate immediate early genes associated with de novo LTP.
      This non-REM sleep-unique genetic environment combined with low acetylcholine
      levels may serve to reduce the strength of cortical circuits that activate in the
      ~50% of delta-coincident reactivation events that do not appear in their waking
      firing sequence. The chapter reviews the results of manipulation studies,
      typically total sleep or REM sleep deprivation, that serve to underscore the
      functional significance of the phenomenological associations. Finally, the
      implications of sleep neurophysiology for learning and memory will be considered
      from a larger perspective in which the association of specific sleep states with
      both potentiation or depotentiation is integrated into mechanistic models of
      cognition.

PMID- 21075233
TI  - Sleep, memory and emotion.
AB  - As critical as waking brain function is to cognition, an extensive literature now
      indicates that sleep supports equally important, different, yet complementary
      operations. This review will consider recent and emerging findings implicating
      sleep, and specific sleep-stage physiologies, in the modulation, regulation and
      even preparation of cognitive and emotional brain processes. First, evidence for
      the role of sleep in memory processing will be discussed, principally focusing on
      declarative memory. Second, at a neural level, several mechanistic models of
      sleep-dependent plasticity underlying these effects will be reviewed, with a
      synthesis of these features offered that may explain the ordered structure of
      sleep, and the orderly evolution of memory stages. Third, accumulating evidence
      for the role of sleep in associative memory processing will be discussed,
      suggesting that the long-term goal of sleep may not be the strengthening of
      individually memory items, but, instead, their abstracted assimilation into a
      schema of generalized knowledge. Forth, the newly emerging benefit of sleep in
      regulating emotional brain reactivity will be considered. Finally, and building
      on this latter topic, a novel hypothesis and framework of sleep-dependent
      affective brain processing will be proposed, culminating in testable predictions
      and translational implications for mood disorders.

PMID- 21075234
TI  - How treatment affects cognitive deficits in patients with sleep disorders:
      methodological issues and results.
AB  - Sleep disorders are frequently associated with impaired performance although the
      type and extent of cognitive deficits varies widely between different types of
      sleep disorders. Treatment is expected to ameliorate these deficits. However,
      cognitive functioning and its change with treatment depend on numerous factors.
      In this chapter we discuss methodological issues, including test selection, and
      person-specific, task-specific and environmental factors that influence cognitive
      functioning. In addition, features of study design and sampling strategies are
      discussed. The chapter ends with a short overview of routes by which treatment
      may affect cognition in sleep-disordered patients.

PMID- 21075235
TI  - Total sleep deprivation, chronic sleep restriction and sleep disruption.
AB  - Sleep loss may result from total sleep deprivation (such as a shift worker might
      experience), chronic sleep restriction (due to work, medical conditions or
      lifestyle) or sleep disruption (which is common in sleep disorders such as sleep
      apnea or restless legs syndrome). Total sleep deprivation has been widely
      researched, and its effects have been well described. Chronic sleep restriction
      and sleep disruption (also known as sleep fragmentation) have received less
      experimental attention. Recently, there has been increasing interest in sleep
      restriction and disruption as it has been recognized that they have a similar
      impact on cognitive functioning as a period of total sleep deprivation. Sleep
      loss causes impairments in cognitive performance and simulated driving and
      induces sleepiness, fatigue and mood changes. This review examines recent
      research on the effects of sleep deprivation, restriction and disruption on
      cognition and neurophysiologic functioning in healthy adults, and contrasts the
      similarities and differences between these three modalities of sleep loss.

PMID- 21075236
TI  - Effects of sleep deprivation on cognition.
AB  - Sleep deprivation is commonplace in modern society, but its far-reaching effects
      on cognitive performance are only beginning to be understood from a scientific
      perspective. While there is broad consensus that insufficient sleep leads to a
      general slowing of response speed and increased variability in performance,
      particularly for simple measures of alertness, attention and vigilance, there is
      much less agreement about the effects of sleep deprivation on many higher level
      cognitive capacities, including perception, memory and executive functions.
      Central to this debate has been the question of whether sleep deprivation affects
      nearly all cognitive capacities in a global manner through degraded alertness and
      attention, or whether sleep loss specifically impairs some aspects of cognition
      more than others. Neuroimaging evidence has implicated the prefrontal cortex as a
      brain region that may be particularly susceptible to the effects of sleep loss,
      but perplexingly, executive function tasks that putatively measure prefrontal
      functioning have yielded inconsistent findings within the context of sleep
      deprivation. Whereas many convergent and rule-based reasoning, decision making
      and planning tasks are relatively unaffected by sleep loss, more creative,
      divergent and innovative aspects of cognition do appear to be degraded by lack of
      sleep. Emerging evidence suggests that some aspects of higher level cognitive
      capacities remain degraded by sleep deprivation despite restoration of alertness
      and vigilance with stimulant countermeasures, suggesting that sleep loss may
      affect specific cognitive systems above and beyond the effects produced by global
      cognitive declines or impaired attentional processes. Finally, the role of
      emotion as a critical facet of cognition has received increasing attention in
      recent years and mounting evidence suggests that sleep deprivation may
      particularly affect cognitive systems that rely on emotional data. Thus, the
      extent to which sleep deprivation affects a particular cognitive process may
      depend on several factors, including the magnitude of global decline in general
      alertness and attention, the degree to which the specific cognitive function
      depends on emotion-processing networks, and the extent to which that cognitive
      process can draw upon associated cortical regions for compensatory support.

PMID- 21075237
TI  - Circadian rhythms and cognition.
AB  - Like all circadian (near-24-h) rhythms, those of cognition have endogenous and
      exogenous components. The origins of these components, together with effects of
      time awake upon cognitive performance, are described in subjects living
      conventionally (sleeping at night and active during the daytime). Based on these
      considerations, predictions can be made about changes that might be expected in
      the days after a time-zone transition and during night work. The relevant
      literature on these circumstances is then reviewed. The last section of the
      chapter deals with sleep-wake schedules where both regular and irregular sleeps
      are taken (anchor sleep).

PMID- 21075238
TI  - The effects of napping on cognitive functioning.
AB  - Naps (brief sleeps) are a global and highly prevalent phenomenon, thus warranting
      consideration for their effects on cognitive functioning. Naps can reduce
      sleepiness and improve cognitive performance. The benefits of brief (5-15 min)
      naps are almost immediate after the nap and last a limited period (1-3h). Longer
      naps (> 30 min) can produce impairment from sleep inertia for a short period
      after waking but then produce improved cognitive performance for a longer period
      (up to many hours). Other factors that affect the benefits from the nap are the
      circadian timing of the nap with early afternoon being the most favourable time.
      Longer periods of prior wakefulness favour longer naps over brief naps. Those who
      regularly nap seem to show greater benefits than those who rarely nap. These
      conclusions, however, need to be accepted cautiously until more comprehensive
      research programmes are conducted in which all these parameters are varied.
      Research is also needed to test the benefits of brief naps taken more
      naturalistically at the time when sleepiness becomes intrusive. The significant
      benefits of a brief nap, containing virtually no slow wave EEG activity, are not
      predicted by the present theory of homeostatic sleep drive (Process S). A new
      biological process (Process O) suggests that sleep onset followed by only 7-10
      min of sleep can result in a substantial increase of alertness because it allows
      the rapid dissipation of inhibition in the 'wake-active' cells associated with
      the 'sleep-switch' mechanism rather than the dissipation of Process S.

PMID- 21075239
TI  - Sleep, intelligence and cognition in a developmental context: differentiation
      between traits and state-dependent aspects.
AB  - This article addresses associations between sleep, cognition and intelligence in
      a developmental context and clarifies the terminology. Research must
      differentiate between aspects related to general underlying traits and those
      aspects that are characterized by state-dependent fluctuations.

PMID- 21075240
TI  - Do sleep complaints contribute to age-related cognitive decline?
AB  - The cognitive changes that occur with ageing are usually referred to as 'age
      related cognitive decline'. The most pronounced changes may be found in the
      executive functions that require integrity of the prefrontal cortical circuitry.
      With age, sleep also changes profoundly, with more sleep fragmentation, earlier
      awakenings and less slow wave sleep as its main features. Interestingly,
      experimental sleep deprivation studies in healthy young adults showed a
      particularly consistent effect on executive functions, suggesting that sleep
      problems might contribute to the cognitive changes accompanying older age. We
      here investigate this possibility by reviewing reports on age-related and
      insomnia-related changes in cognition and brain function and structure, as found
      in studies investigating subjective complaints, objective functioning in everyday
      life, neuropsychological assessment, psychometry, structural and functional
      magnetic resonance imaging, electroencephalography, positron emission tomography
      and transcranial magnetic stimulation. The chapter focuses on the 'normal' age
      related sleep changes that are experienced as insomnia - that is, fragmentation
      of sleep, more superficial sleep, more wake after sleep onset and earlier
      awakenings - rather than on specific sleep disturbances as sleep-disordered
      breathing, restless legs or periodic limb movements during sleep, for all of
      which the risk increases with age. It turned out that relatively few studies
      directly addressed the question whether elderly with different degrees of sleep
      complaints are differentially affected by 'age-related cognitive decline'. Still,
      several similarities between age-related and insomnia-related cognitive and brain
      changes are apparent, notably with respect to performance requiring integrity of
      the prefrontal cortical system. We suggest that at least part of what we regard
      as age-related changes may, in fact, be due to poor sleep, which is in some cases
      a treatable condition. Further research directly comparing aged good sleepers
      versus aged insomniacs will need to elucidate how sleep disturbances are involved
      in the cognitive, structural and functional changes observed with increasing age.
      The findings suggest that discrimination of subtypes of poor sleep at high age
      will aid in understanding the mechanisms by which it affects cognition and brain
      function.

PMID- 21075241
TI  - "Claptrap" from the UK's Department of Health.

PMID- 21075242
TI  - Lack of treatment of South Africa's infants with HIV.

PMID- 21075243
TI  - UK versus US health care: Atlantic rift.

PMID- 21075244
TI  - Croatia moves away from fostering research integrity.

PMID- 21075249
TI  - Ke Yang--reforming medical education in China.

PMID- 21075250
TI  - Arsenic exposure from drinking water and mortality in Bangladesh.

PMID- 21075251
TI  - Arsenic exposure from drinking water and mortality in Bangladesh.

PMID- 21075253
TI  - Vitamin C and E to prevent pre-eclampsia in diabetic women.

PMID- 21075255
TI  - HPV vaccine suspension in India.

PMID- 21075256
TI  - Another lesson unlearned: access to family planning in Niger.

PMID- 21075257
TI  - Hepatosplenic schistosomiasis.

PMID- 21075258
TI  - The influence of women in medicine.

PMID- 21075259
TI  - What have we here? A man or a fish?

PMID- 21075261
TI  - Classic images: coronary computed tomographic angiography.
AB  - A number of congenital and acquired conditions may affect the coronary arteries,
      ranging from very common entities, such as atherosclerotic disease, to very rare
      coronary anomalies. Some of the conditions that affect the coronary arteries are
      unique in the body. As a result, readers of cardiac computed tomography are faced
      with several unique challenges in classifying and stratifying a wide array of
      diseases. Herein, we discuss some of the technical aspects of coronary computed
      tomographic angiography and review the spectrum of coronary abnormalities that
      may be detected with this modality. The typical imaging findings of common and
      uncommon coronary disease states will be demonstrated.

PMID- 21075262
TI  - Life sustaining treatment at end-of-life in Japan: do the perspectives of the
      general public reflect those of the bereaved of patients who had died in
      hospitals?
AB  - OBJECTIVE: To compare the perspectives of the general public and of the bereaved
      of patients who had died in hospitals on life sustaining treatment (LST). METHOD:
      Two self-administered questionnaire surveys were conducted in a city in Japan.
      The general public survey was mailed to a stratified sample of 1000 residents
      aged 20 and over, of which 419 (42%) responded. The bereaved survey was mailed to
      427 family members of patients who had died in the city's 6 hospitals, of which
      205 (48%) responded. RESULTS: In the general public survey, 44% had discussed LST
      with their family; 30% thought physicians discussed them with the patient or
      family; if a family member were to have cancer 57% did not want LST, if frail,
      69%. In the bereaved survey, 39% had discussed LST with the patient; 80% had the
      respondent's preferences followed by the physician; 23% had not wanted LST for
      cancer, 39% for a frail condition. CONCLUSION: The LST preferences of a family
      member were known by less than half of the respondents in both surveys. When
      compared with the general public, the bereaved evaluated the physician's attitude
      more positively and the proportion who did not want LST was less.

PMID- 21075263
TI  - Factors associated with the implementation of quality and safety requirements for
      cross-border care in acute myocardial infarction: Results from 315 hospitals in
      four countries.
AB  - OBJECTIVE: Cross-border patients have specific quality and safety requirements
      for hospital care. Little is known to what extent hospitals meet these
      requirements. We aim to assess their current level, and the factors associated
      with their implementation. METHODS: A cross-sectional survey of 315 hospitals and
      cardiology departments in the Czech Republic, France, Poland and Spain. Employing
      bi-variate statistics and logistic regression analysis, we assess quality and
      safety requirements for cross-border patients and their association with hospital
      characteristics, cross-border care arrangements, proximity to EU borders, the
      hospital's quality improvement system, and country. RESULTS: Certain quality and
      safety requirements are frequently met (administrative support or informed
      consent using forms in various EU languages) while others are widely absent (case
      managers, contacts to patients' general practitioners). Due to communication
      problems, it is often not possible to inform patients about their condition and
      treatment. Discharge summaries are rarely available in other than the vernacular
      languages, and medication upon discharge and arranging back-transfer occur
      occasionally only. Logistic regression analysis suggests a strong effect of
      country-level covariates (followed by type of hospital, hospital size and
      hospital's quality improvement system), but covariates are not consistently
      associated with higher rates of implementation. Hospitals with existing cross
      border care collaboration do not differ substantially from hospitals without such
      arrangements. CONCLUSION: Cross-border patients have specific quality and safety
      requirements that are not always met. Various factors are associated with these
      requirements; however, the trend is not systematic and the underlying mechanisms
      need to be studied further to inform policy decisions.

PMID- 21075264
TI  - Progress in vaccines, progress in health economics.

PMID- 21075265
TI  - Residual economic burden of Streptococcus pneumoniae- and nontypeable Haemophilus
      influenzae-associated disease following vaccination with PCV-7: a multicountry
      analysis.
AB  - This paper estimates the annual direct medical and caregiver costs of
      Streptococcus pneumoniae (Sp) and nontypeable Haemophilus influenzae (NTHi)
      associated diseases in children younger than 10 years in Canada, Germany, Mexico,
      and Norway after vaccination with the 7-valent pneumococcal conjugate vaccine
      (PCV-7). Per-episode direct medical costs for treating Sp- and NTHi-associated
      diseases were summarised from the literature for three countries, and a Delphi
      panel was used to estimate resource use and the per-episode costs for Mexico. Per
      episode or annual costs were inflated to 2008 local currency and converted to
      2008 United States (US) dollars using purchasing power parities. The analysis was
      for 1 year; therefore, costs were not discounted. Sp- and NTHi-associated
      diseases resulted in current annual national costs of $179-$260 million ($5.43
      $7.89 per capita) in Canada, $290-$435 million ($3.53-$5.29 per capita) in
      Germany, $277-$432 million ($2.59-$4.05 per capita) in Mexico, and $20-$28
      million ($4.35-$6.17 per capita) in Norway. Although acute otitis media (AOM) was
      associated with the lowest per-case costs, it accounted for between 45% and 88%
      of the national direct medical costs and between 67% and 96% of caregiver costs
      for Sp- and NTHi-associated diseases. Sp- and NTHi-associated diseases continue
      to result in substantial direct medical and caregiver costs despite current PCV-7
      vaccination programs.

PMID- 21075266
TI  - Outcomes and costs associated with PHiD-CV, a new protein D conjugate
      pneumococcal vaccine, in four countries.
AB  - This study estimated the impact of routine vaccination of infants with a new 10
      valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate
      vaccine (PHiD-CV) on health outcomes and costs across the entire population in
      Canada, Germany, Mexico, and Norway. A compartmental, static model with a 1-year
      time period for a steady-state population that allowed for the incorporation of
      direct and indirect (i.e., herd immunity and serotype replacement) vaccine
      effects across all age groups was used. Cases of disease prevented, deaths
      prevented, life-years gained, quality-adjusted life-years gained, and incremental
      costs in the steady-state year were calculated for PHiD-CV compared with 7-valent
      pneumococcal conjugate vaccine (PCV-7). A short-term analysis was also conducted
      to estimate the incremental difference in disease and cost outcomes for the two
      vaccines within the first 10 years. All costs were in 2008 local currency. In all
      four countries, the model estimated that PHiD-CV prevented more cases of disease,
      prevented more deaths, and resulted in more life-years and quality-adjusted life
      years compared with PCV-7 in both the short term and the steady-state year.
      Assuming price parity for the vaccines, the model projected that routine
      vaccination with PHiD-CV resulted in lower costs compared with PCV-7 in both the
      short term and the steady-state year. Scenario analysis showed the incremental
      cost savings for PHiD-CV compared with PCV-7 in the steady-state year were
      sensitive to assumptions regarding duration of vaccine efficacy.

PMID- 21075267
TI  - A steady-state, population-based model to estimate the direct and indirect
      effects of pneumococcal vaccines.
AB  - This paper estimated the clinical impact of routine vaccination of infants with a
      new 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate
      vaccine (PHiD-CV) compared with the 7-valent pneumococcal conjugate vaccine (PCV
      7) and no vaccination in Canada using a new steady-state, population-based model.
      A deterministic, compartmental model was developed to simulate the effect of
      vaccination for a 1-year time period for a steady-state population, allowing for
      the incorporation of herd and replacement effects across all age groups. Annual
      clinical outcomes in the steady-state year for a population of 32.9 million were
      calculated for all three vaccination strategies. The no vaccination strategy was
      included for the purpose of validating the model. The model estimated that PHiD
      CV prevented more cases of disease and more deaths than PCV-7 and no vaccination,
      with the largest incremental impact on acute otitis media (AOM). Compared with
      PCV-7, vaccination with PHiD-CV was estimated to prevent an additional 10 cases
      of invasive disease, 416 cases of pneumonia, 155,757 cases of AOM, 8943
      myringotomy procedures, and 6 deaths nationwide. For the comparison between PCV-7
      and no vaccination, the model estimated a 36.8% reduction in invasive disease;
      this result was similar to other models and a recent observational study in
      Canada, providing preliminary validation of the model.

PMID- 21075268
TI  - Modelling the effect of conjugate vaccines in pneumococcal disease: cohort or
      population models?
AB  - Cohort and population models estimate vaccine impact on disease events, and yield
      different estimates in countries with different demographic compositions. We
      compared administration of the new 10-valent pneumococcal Haemophilus influenzae
      protein D conjugate vaccine (PHiD-CV) with no vaccination in two countries, the
      United Kingdom (UK) and Mexico, using two modelling strategies: a cohort model
      and a population model. The cohort model followed a birth cohort over a lifetime,
      beginning 10 years after initiation of the vaccine program, when vaccine efficacy
      steady state had been reached. The population model examined the country-specific
      population over 1 year, also beginning 10 years after initiation of the vaccine
      program. Both models included the same age-specific disease rates of meningitis,
      bacteraemia, pneumonia, and otitis media. The output variables were the numbers
      of specific events, with and without indirect vaccine effects. Without indirect
      effects, the cohort and population models produced similar results for both
      countries (deviation of <20% difference per output measure for most outcomes).
      The difference between the model types was much greater when indirect vaccine
      effects were included, especially in Mexico (up to 120% difference). Cohort and
      population modelling methods produce different results depending on the disease,
      the intervention, the demographic composition, and the time horizon evaluated.
      Results from the two model types provide different information about the impact
      of interventions on events: accumulated vaccine benefit for an individual in a
      cohort model; vaccine benefit for a whole population at a specific time point in
      a population model.

PMID- 21075269
TI  - The health care burden and societal impact of acute otitis media in seven
      European countries: results of an Internet survey.
AB  - This paper estimates medical resource use, direct costs, and productivity losses
      and costs (indirect costs) during episodes of acute otitis media (AOM) in young
      children. A 24-item Internet questionnaire was developed for parents in Belgium
      (Flanders), France, Germany, Italy, The Netherlands, Spain, and the United
      Kingdom (UK) to report health care resource use and productivity losses during
      the most recent episode of AOM in their child, younger than 5 years. The
      percentage who did not seek medical help for AOM was considerable in The
      Netherlands (28.3%) and the UK (19.7%). Antibiotic use was high, ranging from
      60.8% (Germany) to 87.1% (Italy). Total costs per AOM episode ranged from ?332.00
      (The Netherlands) to ?752.49 (UK). Losses in productivity accounted for 61%
      (France) to 83% (Germany) of the total costs. AOM poses a significant medical and
      economic burden to society.

PMID- 21075271
TI  - Progress in genomic technology: a new challenge for the palliative medicine?

PMID- 21075272
TI  - Long-term safety and efficacy of morphine sulfate and naltrexone hydrochloride
      extended release capsules, a novel formulation containing morphine and
      sequestered naltrexone, in patients with chronic, moderate to severe pain.
AB  - CONTEXT: Morphine sulfate and naltrexone hydrochloride extended release capsules
      contain extended-release pellets of morphine with a sequestered naltrexone core
      (MS-sNT). Taken whole, as intended, morphine is released to provide pain relief;
      if tampered with by crushing, naltrexone is released to mitigate subjective
      effects of morphine. OBJECTIVES: This open-label study assessed long-term (12
      month) safety of MS-sNT in patients with chronic, moderate to severe pain.
      METHODS: Safety assessments included determining adverse events (AEs), laboratory
      assessments, and the Clinical Opiate Withdrawal Scale (COWS). Analgesic efficacy
      was assessed (diary) as worst, least, average, and current pain using an 11-point
      numeric scale (0=none; 10=worst). RESULTS: Of 465 patients receiving one or more
      doses, 160 completed the study. Most patients (81.3%) experienced one or more
      AEs, most commonly constipation (31.8%) or nausea (25.2%). Thirty-three patients
      (7.1%) reported serious AEs; one patient's severe gastrointestinal inflammation
      and colitis were considered possibly study drug-related. Most discontinuations
      (30%) occurred in the first month, most often because of AEs (23.7%). There were
      no clinically relevant changes in laboratory results or vital signs, and no
      clinically significant electrocardiogram changes deemed study drug-related.
      During each visit after Week 1, 5% or fewer patients had COWS scores indicating
      mild withdrawal symptoms (range, 0%-4.8%). Five patients, who did not take the
      study drug as instructed, had scores consistent with moderate withdrawal. MS-sNT
      yielded statistically significant improvements from baseline in mean scores for
      all pain diary items for all visits, except Week 1 for least pain. CONCLUSION: In
      this study population, when MS-sNT was taken as directed for chronic, moderate to
      severe pain for up to 12 months, most AEs were typical opioid-related side
      effects. Mean COWS scores remained low, indicating lack of withdrawal symptoms
      and appropriate transition off the study drug at completion.

PMID- 21075273
TI  - Consensus recommendations for the management of constipation in patients with
      advanced, progressive illness.
AB  - Constipation is a highly prevalent and distressing symptom in patients with
      advanced, progressive illnesses. Although opioids are one of the most common
      causes of constipation in patients with advanced, progressive illness, it is
      important to note that there are many other potential etiologies and combinations
      of causes that should be taken into consideration when making treatment
      decisions. Management approaches involve a combination of good assessment
      techniques, preventive regimens, appropriate pharmacological treatment of
      established constipation, and frequent monitoring. In this vulnerable patient
      population, maintenance of comfort and respect for individual preferences and
      sensitivities should be overriding considerations when making clinical decisions.
      This consensus document was developed by a multidisciplinary group of leading
      Canadian palliative care specialists in an effort to define best practices in
      palliative constipation management that will be relevant and useful to health
      care professionals. Although a wide range of options exists to help treat
      constipation and prevent its development or recurrence, there is a limited body
      of evidence evaluating pharmacological interventions. These recommendations are,
      therefore, based on the best of the available evidence, combined with expert
      opinion derived from experience in clinical practice. This underscores the need
      for further clinical evaluation of the available agents to create a robust,
      evidence-based foundation for treatment decisions in the management of
      constipation in patients with advanced, progressive illness.

PMID- 21075274
TI  - Psychostimulants.

PMID- 21075275
TI  - Poetry and healing at the end of life.

PMID- 21075276
TI  - Preface. Thalassemia.

PMID- 21075277
TI  - Thalassemia: an overview of 50 years of clinical research.
AB  - The thalassemias are attributable to the defective production of the alpha- and
      beta-globin polypeptides of hemoglobin. Significant discoveries have illuminated
      the pathophysiology and enhanced the prevention and treatment of the
      thalassemias, and this article reviews many of the advances that have occurred in
      the past 50 years. However, the application of new approaches to the treatment of
      these disorders has been slow, particularly in the developing world where the
      diseases are common, but there is definite progress. This article emphasizes how
      the increasing knowledge of cellular and molecular biology are facilitating the
      development of more effective therapies for these patients.

PMID- 21075278
TI  - The population genetics and dynamics of the thalassemias.
AB  - The inherited disorders of hemoglobin, including the thalassemias, are by far the
      commonest monogenic diseases. Although several factors are responsible for their
      very high frequency, the major mechanism seems to be natural selection mediated
      by heterozygote protection against severe forms of malaria. Recent work has
      highlighted the complexity of the interplay among the different hemoglobin
      variants themselves and among different levels of malaria resistance, and is
      helping to explain the extraordinary heterogeneity in the distribution of the
      hemoglobin disorders even within short geographical distances. Some progress has
      also been made toward understanding the cellular and immune mechanisms that may
      underlie heterozygote protection against malaria in these conditions. In addition
      to providing valuable information about human evolutionary biology, work in this
      field has an increasingly important influence on the development of programs for
      the better management of the hemoglobin disorders, particularly in the poorer
      countries of the tropical world.

PMID- 21075279
TI  - The molecular basis of alpha-thalassemia: a model for understanding human
      molecular genetics.
AB  - Down-regulation of alpha-globin synthesis causes alpha-thalassemia with
      underproduction of fetal (HbF, alpha(2)gamma(2)) and adult (HbA, alpha(2)beta(2))
      hemoglobin. This article focuses on the human alpha-globin cluster, which has
      been characterized in great depth over the past 30 years. In particular the
      authors describe how the alpha genes are normally switched on during
      erythropoiesis and switched off as hematopoietic stem cells commit to
      nonerythroid lineages. In addition, the principles by which alpha-globin
      expression may be perturbed by natural mutations that cause alpha-thalassemia are
      reviewed.

PMID- 21075280
TI  - HbE/beta-thalassemia: basis of marked clinical diversity.
AB  - Hemoglobin E thalassemia accounts for about one-half of all cases of severe beta
      thalassemia. There is marked variability in its clinical severity ranging from an
      asymptomatic to a transfusion-dependent phenotype. The phenotypic variability and
      inadequate longitudinal data present challenges in determining the optimal
      management of patients. This article summarizes findings on the natural history
      of Hemoglobin E thalassemia and some factors responsible for its clinical
      heterogeneity. Major genetic factors include the type of beta thalassemia
      mutation, the co-inheritance of alpha thalassemia, and polymorphisms associated
      with increased synthesis of fetal hemoglobin. Other factors, including response
      to anemia, and the influence of infection with malaria and other environmental
      influences, may be important. The remarkable variation and instability of
      clinical phenotypes in Hemoglobin E thalassemia require individual management
      plans for each patient, which should be reassessed over time.

PMID- 21075283
TI  - Iron overload in thalassemia and related conditions: therapeutic goals and
      assessment of response to chelation therapies.
AB  - Transfusional iron loading inevitably results in hepatic iron accumulation, with
      variable extrahepatic distribution that is typically less pronounced in sickle
      cell disease than in thalassemia disorders. Iron chelation therapy has the goal
      of preventing iron-mediated tissue damage through controlling tissue iron levels,
      without incurring chelator-mediated toxicity. Historically, target levels for
      tissue iron control have been limited by the increased frequency of deferoxamine
      mediated toxicity and low levels of iron loading. With newer chelation regimes,
      these limitations are less evident. The reporting of responses to chelation
      therapies has typically focused on average changes in serum ferritin in patient
      populations. This approach has three limitations. First, changes in serum
      ferritin may not reflect trends in iron balance equally in all patients or for
      all chelation regimens. Second, this provides no information about the proportion
      of patients likely respond. Third, this gives insufficient information about iron
      trends in tissues such as the heart. Monitoring of iron overload has advanced
      with the increasing use of MRI techniques to estimate iron balance (changes in
      liver iron concentration) and extrahepatic iron distribution (myocardial T2*).
      The term nonresponder has been increasingly used to describe individuals who fail
      to show a downward trend in one or more of these variables. Lack of a response of
      an individual may result from inadequate dosing, high transfusion requirement,
      poor treatment adherence, or unfavorable pharmacology of the chelation regime.
      This article scrutinizes evidence for response rates to deferoxamine, deferiprone
      (and combinations), and deferasirox.

PMID- 21075284
TI  - Pharmacologic induction of fetal hemoglobin production.
AB  - Reactivation of fetal hemoglobin (HbF) expression is an important therapeutic
      option in adult patients with hemoglobin disorders. The understanding of the
      developmental regulation of gamma-globin gene expression was followed by the
      identification of a number of chemical compounds that can reactivate HbF
      synthesis in vitro and in vivo in patients with hemoglobin disorders. These HbF
      inducers can be grouped in several classes based on their mechanisms of action.
      This article focuses on pharmacologic agents that were tested in humans and
      discusses current knowledge about the mechanisms by which they induce HbF.

PMID- 21075285
TI  - Allogeneic cellular gene therapy for hemoglobinopathies.
AB  - Hematopoietic stem cell transplantation (HSCT) offers potentially curative
      therapy for patients with thalassemia major and sickle cell disease (SCD).
      Current myeloablative treatment protocols allow the cure of 78% to 90% of
      patients with thalassemia and 72% to 96% with SCD, depending on disease status at
      the time of transplantation. The major limitation to successful transplantation
      is the lack of a suitable HLA-matched family donor. Unrelated donor HSCT is now
      extensively used to treat thalassemia, with results similar to those obtained
      following transplantation using HLA-matched sibling donors. Patients who lack a
      matched related or unrelated donor can now benefit from successful
      transplantation using haploidentical donors.

PMID- 21075286
TI  - Umbilical cord blood transplantation for thalassemia major.
AB  - Hematopoietic cell transplantation is curative therapy for thalassemia major.
      Although the clinical application of hematopoietic cell transplantation has
      relied on marrow collected from related and unrelated donors as the primary
      source of donor hematopoietic cells, umbilical cord blood (UCB) is an alternative
      source of hematopoietic cells and represents a suitable allogeneic donor pool in
      the event that a marrow donor is not available. Progress in developing UCB
      transplantation for thalassemia is reviewed and the most likely areas of future
      clinical investigation are discussed.

PMID- 21075281
TI  - Protein quality control during erythropoiesis and hemoglobin synthesis.
AB  - Erythrocytes must regulate hemoglobin synthesis to limit the toxicities of
      unstable free globin chain subunits. This regulation is particularly relevant in
      beta-thalassemia, in which beta-globin deficiency causes accumulation of free
      alpha-globin, which forms intracellular precipitates that destroy erythroid
      precursors. Experimental evidence accumulated over more than 40 years indicates
      that erythroid cells can neutralize moderate amounts of free alpha-globin through
      generalized protein quality control mechanisms, including molecular chaperones,
      the ubiquitin-proteasome system, and autophagy. In many ways, beta-thalassemia
      resembles protein aggregation disorders of the nervous system, liver, and other
      tissues, which occur when levels of unstable proteins overwhelm cellular
      compensatory mechanisms. Information gained from studies of nonerythroid protein
      aggregation disorders may be exploited to further understand and perhaps treat
      beta-thalassemia.

PMID- 21075282
TI  - Anemia, ineffective erythropoiesis, and hepcidin: interacting factors in abnormal
      iron metabolism leading to iron overload in beta-thalassemia.
AB  - beta-Thalassemia is a genetic disorder caused by mutations in the beta-globin
      gene and characterized by chronic anemia caused by ineffective erythropoiesis,
      and accompanied by a variety of serious secondary complications such as
      extramedullary hematopoiesis, splenomegaly, and iron overload. In the past few
      years, numerous studies have shown that such secondary disease conditions have a
      genetic basis caused by the abnormal expression of genes with a role in
      controlling erythropoiesis and iron metabolism. In this article, the most recent
      discoveries related to the mechanism(s) responsible for anemia/ineffective
      erythropoiesis and iron overload are discussed in detail. Particular attention is
      paid to the pathway(s) controlling the expression of hepcidin, which is the main
      regulator of iron metabolism, and the Epo/EpoR/Jak2/Stat5 signaling pathway,
      which regulates erythropoiesis. Better understanding of how these pathways
      function and are altered in beta-thalassemia has revealed several possibilities
      for development of new therapeutic approaches to treat of the complications of
      this disease.

PMID- 21075287
TI  - Noninvasive approaches to prenatal diagnosis of hemoglobinopathies using fetal
      DNA in maternal plasma.
AB  - Fetal DNA is present in the plasma of pregnant women and can be used for
      noninvasive prenatal diagnosis. Early work had focused on the detection of
      paternally inherited fetal mutations in maternal plasma. Recent advances in
      single-molecule counting approaches have allowed the mutation dosage of the fetus
      to be analyzed in maternal plasma. These developments have been demonstrated as
      feasible for noninvasive prenatal diagnosis of several hemoglobinopathies,
      including beta-thalassemia and hemoglobin E disease.

PMID- 21075288
TI  - Hemoglobin gene therapy for beta-thalassemia.
AB  - Allogeneic stem cell transplantation currently is the only curative option for
      severe beta-thalassemia and sickle cell disease. Human globin gene therapy with
      autotransplantation of transduced human hematopoietic stem cells is an exciting
      alternative approach to a potential cure. One patient with thalassemia has
      recently been reported to have clinical benefit after lentiviral human beta
      globin gene therapy. He has not required blood transfusions for almost 2 years.
      Most of the patient's gene correction and new human beta-globin gene expression
      is caused by the expansion of a single clone in which the corrective transgene is
      inserted into an Hmga2 gene.

PMID- 21075291
TI  - [Ethics in nursing research].

PMID- 21075289
TI  - Mouse models of inherited cancer syndromes.
AB  - Animal models of cancer have been instrumental in understanding the progression
      and therapy of hereditary cancer syndromes. The ability to alter the genome of an
      individual mouse cell in both constitutive and inducible approaches has led to
      many novel insights into their human counterparts. In this review, knockout mouse
      models of inherited human cancer syndromes are presented and insights from the
      study of these models are highlighted.

PMID- 21075292
TI  - United Kingdom and Ireland Association of Forensic Toxicologists: guidelines for
      forensic toxicology laboratories.

PMID- 21075294
TI  - A preliminary investigation into the comparison of dissolution/digestion
      techniques for the chemical characterization of polyurethane foam.
AB  - Due to their widespread use in domestic and commercial premises, polyurethane
      foams, as either fragmented or bulk foam, are types of evidence commonly found at
      crime scenes. The traditional approach to determining the evidential value of
      polyurethane foam (PF) involves comparing recovered and control fragments under
      low and high magnification, under various lighting conditions, as well as the
      comparison of their respective dye spectra. As with most forms of trace evidence,
      chemical comparison is also desirable. In this work, two approaches to chemically
      comparing foam fragments were investigated, i.e. inductively coupled plasma
      optical emission spectrometry (ICP-OES) analysis of the Tin (Sn) content in
      different foam types; and gas chromatography-flame ionization detection (GC-FID)
      analysis of soluble components in PFs mobilized by dichloromethane. Seven
      different foam types were studied and their Sn content was found to be different.
      They also produced characteristic GC-FID chromatographic profiles whose compounds
      were identified with gas chromatography-mass spectrometry (GC-MS) analysis. This
      study suggests that incorporating chemical data obtained from GC-FID/GC-MS and
      ICP-OES into a case involving PF could be advantageous, as this will enable the
      forensic scientist to broaden the comparison between control and recovered
      fragments, and further assess the strength of the evidence. However, ICP-OES
      analysis is a destructive technique with a relatively short sample turnaround
      time, whilst GC-FID analysis is more time-consuming and non-destructive,
      requiring corroboration with GC-MS data. The values of these two analytical
      techniques in the forensic chemical characterization of PFs are discussed.

PMID- 21075293
TI  - The United Kingdom and Ireland Association of Forensic Toxicologists Forensic
      toxicology laboratory guidelines (2010).

PMID- 21075295
TI  - Ten methods for calculating the uncertainty of measurement.
AB  - While forensic laboratories are coming under increasing pressure to provide
      meaningful estimates of measurement uncertainty, there has been little discussion
      of this topic in the literature. This article summarizes ten bases for estimating
      this parameter: (1) proficiency tests; (2) readability limits; (3) independent
      reference materials; (4) operational limits applied during calibration; (5)
      expert judgment; (6) precision control samples without (6) and with (7)
      contributions from extramural sources of error; (8) error budgets; (9) historical
      performance; and (10) ruggedness tests. Based on the assumptions underlying each
      approach, the forensic community will need to apply a variety of discipline
      specific approaches to arrive at satisfactory estimates of measurement
      uncertainty.

PMID- 21075296
TI  - "Flashburning"--interpreting the presence of heat damage to a suspect's clothing
      and footwear in the investigation of fires.
AB  - When volatile flammable vapours are released, they can mix with surrounding air
      and form a vapour cloud. Ignition of this fuel/air mixture will produce a flame
      front that will flash through the vapour. Items exposed to the flame front,
      including a suspect's clothing and footwear, may sustain superficial heat damage.
      At The Forensic Science Service Ltd this is referred to as flashburning. This
      paper describes the concept of flashburning, the laboratory methodology used to
      identify it and how an assessment on the overall distribution of that damage may
      allow a scientist to evaluate its evidential significance. Two anonymised
      casework examples are used to demonstrate how this information has been
      interpreted and used in evidence in United Kingdom courts of law.

PMID- 21075297
TI  - Evaluation of the shedding potential of textile materials.
AB  - A practical method is proposed to assess the shedding potential of textile
      materials. The evaluation of the sheddability is based on the use of adhesive
      tapes and on comparison, using three different sheddability scales for cotton,
      wool and fine man-made fibres.

PMID- 21075290
TI  - Lower gastrointestinal tract cancer predisposition syndromes.
AB  - Although inherited predisposition to colorectal cancer (CRC) has been suspected
      for more than 100 years, definitive proof of Mendelian syndromes had to await
      maturation of molecular genetic technologies. Since the l980s, the genetics of
      several clinically distinct entities has been revealed. Five disorders that share
      a hereditary predisposition to CRC are reviewed in this article.

PMID- 21075298
TI  - The reincorporation and redistribution of trace geoforensic particulates on
      clothing: an introductory study.
AB  - Two experimental studies were undertaken to investigate the processes of
      reincorporation and redistribution of trace evidence on garments when worn by a
      suspect or a victim (reincorporation) or after the garments have been seized and
      packaged for subsequent forensic analysis (redistribution). The first experiment
      utilised UV powder, an established proxy for geoforensic trace particulates and
      the second experiment utilised daffodil pollen transferred onto garments under
      conditions that mimicked forensic reality. It was demonstrated that
      reincorporation of trace particulates occurs from upper to lower parts of the
      same garment and also from upper garments to lower garments. Reincorporation also
      occurred to all areas of the lower garments, however the highest concentration of
      particulates was found to be the lap area of the jeans. Particulates also tended
      to be preserved around technical details such as stitching or relief design
      features of the garments. Thus the decay of particulates after a contact has been
      made does not necessarily involve a loss of those particulates from the entire
      system. These findings have implications for the interpretation of trace evidence
      when seeking to establish the source of initial contacts or the chronology of
      pertinent events. The second study demonstrated that folding and packaging items
      of clothing leads to a redistribution of any trace particulate evidence that is
      present thereby eliciting an alteration in the spatial distribution of that
      evidence. There is therefore a necessity to take the context of trace evidence
      into account and also to follow protocols that are sensitive to these aspects of
      trace evidence behaviour as a failure to do so may have consequences for the
      correct interpretation of such evidence.

PMID- 21075299
TI  - Chemical enhancement of footwear impressions in blood deposited on fabric-
      evaluating the use of alginate casting materials followed by chemical
      enhancement.
AB  - Most footwear marks made in blood on a surface such as fabric tend to be enhanced
      in situ rather than physically recovered using a lifting technique prior to
      enhancement. This work reports on the use of an alginate material to recover the
      impressed footwear marks made in blood and deposited on a range of fabric types
      and colours. The lifted marks were then enhanced using acid black 1 and leuco
      crystal violet with excellent results. This presents a new method for the lifting
      and recovery of blood impressions in situ from crime scene followed by subsequent
      mark enhancement of the lifted impression.

PMID- 21075300
TI  - Calculating likelihood ratios for a mixed DNA profile when a contribution from a
      genetic relative of a suspect is proposed.
AB  - This technical note describes a practical method for evaluating evidence in the
      case of a two person conditioned DNA mixture where the defence proposition is
      that the unknown contributor is genetically related to the suspect. A conditioned
      mixture is one where the presence of DNA from one of two individuals is accepted
      by both prosecution and defence. A typical example would be a vaginal swab in an
      alleged rape case, where the presence of the complainant's DNA would be expected
      and samples have been taken from the complainant and a suspect. Much has been
      written about the interpretation of such mixtures and the calculation of the
      conditional genotype probabilities that must be carried out. In general, such
      treatments assume that the unknown contributor, under the defence proposition, is
      unrelated to the known individuals. In this paper, we consider the case where the
      defence proposition is that the unknown contributor is genetically related to the
      suspect. We describe a method, incorporating a flow chart and reference tables
      that facilitate manual calculations of the likelihood ratio for several
      postulated genetic relationships.

PMID- 21075301
TI  - Pharmacological rescue of p53 in cancer therapy: widening the sensitive tumor
      spectrum by targeting MDMX.

PMID- 21075302
TI  - Unfavorable drug interactions in targeted breast cancer therapy.

PMID- 21075303
TI  - Can antitumor immunity help to explain "oncogene addiction"?

PMID- 21075305
TI  - Bioinformatic mining of gene expression datasets identifies ETV1 as a critical
      regulator of oncogenesis in gastrointestinal stromal tumors.

PMID- 21075304
TI  - STATistical power of clonal analysis: differential STAT1 pathway activation
      downstream of the JAK2V617F mutation.

PMID- 21075306
TI  - An identity crisis for a cancer gene: subcellular location determines ASPP1
      function.

PMID- 21075307
TI  - A stapled p53 helix overcomes HDMX-mediated suppression of p53.
AB  - Cancer cells neutralize p53 by deletion, mutation, proteasomal degradation, or
      sequestration to achieve a pathologic survival advantage. Targeting the E3
      ubiquitin ligase HDM2 can lead to a therapeutic surge in p53 levels. However, the
      efficacy of HDM2 inhibition can be compromised by overexpression of HDMX, an HDM2
      homolog that binds and sequesters p53. Here, we report that a stapled p53 helix
      preferentially targets HDMX, blocks the formation of inhibitory p53-HDMX
      complexes, induces p53-dependent transcriptional upregulation, and thereby
      overcomes HDMX-mediated cancer resistance in vitro and in vivo. Importantly, our
      analysis of p53 interaction dynamics provides a blueprint for reactivating the
      p53 pathway in cancer by matching HDM2, HDMX, or dual inhibitors to the
      appropriate cellular context.

PMID- 21075308
TI  - Recombinant human erythropoietin antagonizes trastuzumab treatment of breast
      cancer cells via Jak2-mediated Src activation and PTEN inactivation.
AB  - We found that the receptor for erythropoietin (EpoR) is coexpressed with human
      epidermal growth factor receptor-2 (HER2) in a significant percentage of human
      breast tumor specimens and breast cancer cell lines. Exposure of HER2 and EpoR
      dual-positive breast cancer cells to recombinant human erythropoietin (rHuEPO)
      activated cell signaling. Concurrent treatment of the cells with rHuEPO and
      trastuzumab reduced the cells' response to trastuzumab both in vitro and in vivo.
      We identified Jak2-mediated activation of Src and inactivation of PTEN as
      underlying mechanisms through which rHuEPO antagonizes trastuzumab-induced
      therapeutic effects. Furthermore, we found that compared with administration of
      trastuzumab alone, concurrent administration of rHuEPO and trastuzumab correlated
      with shorter progression-free and overall survival in patients with HER2-positive
      metastatic breast cancer.

PMID- 21075309
TI  - Hdac3 is essential for the maintenance of chromatin structure and genome
      stability.
AB  - Hdac3 is essential for efficient DNA replication and DNA damage control. Deletion
      of Hdac3 impaired DNA repair and greatly reduced chromatin compaction and
      heterochromatin content. These defects corresponded to increases in histone
      H3K9,K14ac; H4K5ac; and H4K12ac in late S phase of the cell cycle, and histone
      deposition marks were retained in quiescent Hdac3-null cells. Liver-specific
      deletion of Hdac3 culminated in hepatocellular carcinoma. Whereas HDAC3
      expression was downregulated in only a small number of human liver cancers, the
      mRNA levels of the HDAC3 cofactor NCOR1 were reduced in one-third of these cases.
      siRNA targeting of NCOR1 and SMRT (NCOR2) increased H4K5ac and caused DNA damage,
      indicating that the HDAC3/NCOR/SMRT axis is critical for maintaining chromatin
      structure and genomic stability.

PMID- 21075310
TI  - Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal
      cells.
AB  - Mutational activation of KRas is the first and most frequently detected genetic
      lesion in pancreatic ductal adenocarcinoma (PDAC). However, the precise role of
      oncogenic KRas in the pathogenesis of PDAC is not fully understood. Here, we
      report that the endogenous expression of oncogenic KRas suppresses premature
      senescence in primary pancreatic duct epithelial cells (PDEC). Oncogenic KRas
      mediated senescence bypass is conferred by the upregulation of the basic helix
      loop-helix transcription factor Twist that in turn abrogates p16(INK4A)
      induction. Moreover, the KRas-Twist-p16(INK4A) senescence bypass pathway is
      employed in vivo to prevent inflammation-associated senescence of pancreatic
      ductal epithelium. Our findings indicate that oncogenic KRas could contribute to
      PDAC initiation by protecting cells from entering a state of permanent growth
      arrest.

PMID- 21075311
TI  - B55beta-associated PP2A complex controls PDK1-directed myc signaling and
      modulates rapamycin sensitivity in colorectal cancer.
AB  - The PP2A serine/threonine protein phosphatase serves as a critical cellular
      regulator of cell growth, proliferation, and survival. However, how this pathway
      is altered in human cancer to confer growth advantage is largely unknown. Here,
      we show that PPP2R2B, encoding the B55beta regulatory subunit of the PP2A
      complex, is epigenetically inactivated by DNA hypermethylation in colorectal
      cancer. B55beta-associated PP2A interacts with PDK1 and modulates its activity
      toward Myc phosphorylation. On loss of PPP2R2B, mTORC1 inhibitor rapamycin
      triggers a compensatory Myc phosphorylation in PDK1-dependent, but PI3K and AKT
      independent manner, resulting in resistance. Reexpression of PPP2R2B, genetic
      ablation of PDK1 or pharmacologic inhibition of PDK1 abrogates the rapamycin
      induced Myc phosphorylation, leading to rapamycin sensitization. Thus, PP2A
      B55beta antagonizes PDK1-Myc signaling and modulates rapamycin sensitivity.

PMID- 21075312
TI  - FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal
      tumorigenesis.
AB  - mTORC1 is a validated therapeutic target for renal cell carcinoma (RCC). Here,
      analysis of Tsc1-deficient (mTORC1 hyperactivation) mice uncovered a FoxO
      dependent negative feedback circuit constraining mTORC1-mediated renal
      tumorigenesis. We document robust FoxO activation in Tsc1-deficient benign
      polycystic kidneys and FoxO extinction on progression to murine renal tumors;
      murine renal tumor progression on genetic deletion of both Tsc1 and FoxOs; and
      downregulated FoxO expression in most human renal clear cell and papillary
      carcinomas, yet continued expression in less aggressive RCCs and benign renal
      tumor subtypes. Mechanistically, integrated analyses revealed that FoxO-mediated
      block operates via suppression of Myc through upregulation of the Myc
      antagonists, Mxi1-SRalpha and mir-145, establishing a FoxO-Mxi1-SRalpha/mir-145
      axis as a major progression block in renal tumor development.

PMID- 21075313
TI  - Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is
      reversible and not hierarchically organized.
AB  - We investigated whether melanoma is hierarchically organized into phenotypically
      distinct subpopulations of tumorigenic and nontumorigenic cells or whether most
      melanoma cells retain tumorigenic capacity, irrespective of their phenotype. We
      found 28% of single melanoma cells obtained directly from patients formed tumors
      in NOD/SCID IL2Rgamma(null) mice. All stage II, III, and IV melanomas obtained
      directly from patients had common tumorigenic cells. All tumorigenic cells
      appeared to have unlimited tumorigenic capacity on serial transplantation. We
      were unable to find any large subpopulation of melanoma cells that lacked
      tumorigenic potential. None of 22 heterogeneously expressed markers, including
      CD271 and ABCB5, enriched tumorigenic cells. Some melanomas metastasized in mice,
      irrespective of whether they arose from CD271(-) or CD271(+) cells. Many markers
      appeared to be reversibly expressed by tumorigenic melanoma cells.

PMID- 21075314
TI  - Prevention: a new focus for the country but old stuff for pediatricians.

PMID- 21075315
TI  - Resident work duty hour requirements: medical educators' perspectives.

PMID- 21075316
TI  - "Just be respectful of the primary doc": teaching mutual respect as a dimension
      of teamwork in general pediatrics.
AB  - OBJECTIVE: Although others have reported on teamwork training, little is known
      about what pediatric residents in inpatient settings learn implicitly about
      respectful working relationships with community-based general pediatricians. The
      purpose of this brief report is to examine how pediatric residents on an
      inpatient general pediatric rotation regard "the other" (community-based general
      pediatricians), and how academic, hospital-based general pediatric attending
      physicians respond. METHODS: We conducted a case study on one general pediatrics
      floor, which entailed 143 hours of observation over 8 months (January to August
      2006), as well as in-depth interviews with 25 residents and 14 general pediatric
      attending physicians whom we observed as they worked on the floor. Data were
      derived from >1000 pages of field notes and interview transcripts. We
      systematically reviewed the data and inductively derived codes related to
      explicit and implicit education. In this brief report, we focused our analysis on
      data relevant to the concept of boundary crossing: when members of the group talk
      about members of another group in the process of inquiring about or negotiating
      patient care. RESULTS: Residents' comments tended to reveal a neutral or somewhat
      negative regard for their general pediatric community counterparts, whom they
      typically referred to as PMDs (primary medical doctors). Attending physicians'
      responses to these comments varied, but often explicitly taught residents about
      dimensions of teamwork, including mutual respect. CONCLUSIONS: Explicit teamwork
      training in pediatric education should not be limited to partnering with other
      disciplines or other specialties, but expanded to enhance positive regard and
      mutual respect for general pediatricians in hospital- and community-based
      settings alike. Attending physicians in general pediatrics are ideally positioned
      to implicitly teach respectful working relationships within the specialty.

PMID- 21075317
TI  - Bed sharing among black infants and sudden infant death syndrome: interactions
      with other known risk factors.
AB  - OBJECTIVE: Bed sharing has been associated with sudden infant death syndrome
      (SIDS) and may contribute to the racial disparity seen in infant mortality. It is
      unclear how bed sharing interacts with other factors to impact SIDS risk. We
      aimed to measure the effects of bed sharing on risk of SIDS in blacks and to
      determine whether the risk is modified by other characteristics of the sleep
      environment. METHODS: Characteristics of 195 black infants who died of SIDS were
      compared with matched controls. The moderating influence of known SIDS risk
      factors on the effect of bed sharing on risk of SIDS was examined using logistic
      regression. RESULTS: Almost half (47.4%) of the study population bed shared
      during the last/reference sleep (58% cases and 37% controls). Bed sharing was
      associated with 2 times greater risk of SIDS compared with not bed sharing. The
      deleterious effect of bed sharing was more pronounced with a soft sleep surface,
      pillow use, maternal smoking, and younger infant age. However, bed sharing was
      still associated with an increased risk of SIDS, even when the infant was not
      using a pillow or sleeping on a firm surface. The strongest predictors of SIDS
      among bed-sharing infants were soft sleep surface, nonuse of a pacifier, and
      maternal smoking during pregnancy. CONCLUSIONS: Bed sharing is a common practice
      among black infants. It is associated with a clear and strong increased risk of
      SIDS, which is even greater when combined with other known risk factors for SIDS.
      This practice likely contributes to the excess incidence of SIDS among blacks,
      and culturally competent education methods must be developed to target this high
      risk group.

PMID- 21075319
TI  - A case-control study to evaluate Utah's shaken baby prevention program.
AB  - OBJECTIVE: Educational programs designed to inform mothers and other child
      caretakers about the dangers of infant shaking have been widely adopted; however,
      only one has been evaluated to ascertain its effect on abusive head trauma (AHT).
      This project's goal was to evaluate whether an educational video delivered on the
      postpartum ward decreased AHT occurrence. METHODS: A case-control study was
      conducted in which 77 Utah resident mothers of children aged under 2 years who
      had AHT were drawn from the only pediatric level-one trauma center in Utah and
      the Medical Examiner's Office from 2001 to 2007. Five control mothers per case
      matched by birth year were identified through the state's birth certificate
      registry. Conditional logistic regression was used to calculate the adjusted odds
      of AHT given maternal exposure to the educational video. An alternate injury and
      alternate educational exposures were assessed to examine potential confounding.
      RESULTS: The educational video was associated with nonstatistically significant
      reductions of both AHT (odds ratio [OR] 0.7, 95% confidence interval [CI], 0.5
      1.2) and the alternate injury mechanism, child injury from motor vehicle crash
      (OR 0.9, 95% CI, 0.6-1.4). Alternate education about car seat use (OR 0.4, 95%
      CI, 0.2-0.8), back to sleep (OR 0.3, 95% CI, 0.2-0.5), and setting hot water
      temperature (OR 0.2, 95% CI, 0.1-0.4) were associated with significant reductions
      in AHT. CONCLUSIONS: AHT occurrence was not significantly associated with the
      educational video but was associated with alternate postpartum education provided
      to mothers. These results suggest that the shaken baby prevention video is not
      causal at reducing AHT.

PMID- 21075318
TI  - Maternal assessment of physician qualification to give advice on AAP-recommended
      infant sleep practices related to SIDS.
AB  - OBJECTIVE: The American Academy of Pediatrics (AAP) strongly recommends the
      supine-only sleep position for infants and issued 2 more sudden infant death
      syndrome (SIDS) reduction recommendations: avoid bed sharing and use pacifiers
      during sleep. In this study, we investigated the following: 1) if mothers from at
      risk populations rate physicians as qualified to give advice about sleep
      practices and 2) if these ratings were associated with reports of recommended
      practice. METHODS: A cross-sectional survey of mothers (N=2355) of infants aged
      <8 months was conducted at Women, Infants, and Children (WIC) Program centers in
      6 cities from 2006 to 2008. The predictor measures were maternal rating of
      physician qualification to give advice about 3 recommended sleep practices and
      reported nature of physician advice. The dependent measures were maternal report
      of usage of recommended behavior: 1) "infant usually placed supine for sleep," 2)
      "infant usually does not share a bed with an adult during sleep," and 3) "infant
      usually uses a pacifier during sleep." RESULTS: Physician qualification ratings
      varied by topic: sleep position (80%), bed sharing (69%), and pacifier use (60%).
      High ratings of physician qualification were associated with maternal reports of
      recommended behavior: supine sleep (adjusted odds ratio [AOR] 2.1, 95% confidence
      interval [CI], 1.6-2.6); usually no bed sharing (AOR 1.5, 95% CI, 1.2-1.9), and
      usually use a pacifier during sleep (AOR 1.2, 95% CI, 1.0-1.5). CONCLUSIONS: High
      maternal ratings of physician qualification to give advice on 2 of the 3
      recommended sleep practices targeted to reduce the risk of SIDS were
      significantly associated with maternal report of using these behaviors. Lower
      ratings of physician qualification to give advice about these sleep practices may
      undermine physician effectiveness in promoting the recommended behavior.

PMID- 21075320
TI  - Use of drugs known to cause fetal harm among women delivering infants in Haiti.
AB  - OBJECTIVE: To estimate the prevalence of use of fetal-harm drugs among women who
      received postpartum care in hospitals in Haiti and to identify groups of women at
      higher risk for potentially harmful medication exposures. METHODS: Women who
      received postpartum care in 2 large hospitals in Port-au-Prince, Haiti, from
      August 18 to December 1, 2008, were surveyed in Creole about their use of
      medications in pregnancy, including fetal-harm drugs. RESULTS: We surveyed 482
      women who had a median age of 26 years. Approximately 75% reported using at least
      1 medicine in pregnancy, with the most common being amoxicillin (n = 127),
      acetaminophen (n = 109), metronidazole (n = 79), and misoprostol (n = 38). More
      than 13% used fetal-harm drugs, including misoprostol and tetracycline. Unmarried
      women (adjusted relative risk [RR] 2.2; 95% confidence interval [CI], 1.0-4.7)
      and separated women (adjusted RR 4.6; CI, 1.8-11.9) were more likely than married
      women to report use of fetal-harm drugs. In addition, women with 4 or more
      children were more likely to report use of medications known to cause fetal harm
      (adjusted RR 4.3; CI, 1.9-9.9). CONCLUSION: Women who delivered infants in Haiti
      commonly report use of fetal-harm drugs. The public health implications of these
      findings are broad and relate to complex issues such as pregnancy planning and
      regulation of medications to prevent potentially harmful exposures.

PMID- 21075321
TI  - An update on assessing development in the pediatric office: has anything changed
      after two policy statements?
AB  - OBJECTIVE: The aim of this study was to examine parental reports of receiving a
      child developmental assessment (DA), and the child, family, and type of health
      care setting characteristics and well-child care processes associated with
      receiving this aspect of preventive developmental care. METHODS: The 2007
      National Survey of Children's Health was used to study 16 223 children, aged 10
      months to 4 years, who received a DA with a structured questionnaire from their
      primary care provider in the previous 12 months. Data were adjusted for child
      characteristics, family socioeconomic factors, type of health care setting, and
      processes of care. RESULTS: Few children were assessed for developmental delays
      by using developmental questionnaires (28%). A greater percentage of parents of
      children with public insurance reported receiving a developmental questionnaire
      compared with parents of children who were uninsured or privately insured (32% vs
      26% and 25%, respectively; P = .02). The adjusted odds of receiving a
      developmental questionnaire were higher for children with public insurance than
      private insurance (odds ratio [OR] 1.35, 95% confidence interval [CI], 1.05
      1.73), higher for children whose usual place of care was a clinic or health
      center than a doctor's office (OR 1.36, 95% CI, 1.07-1.74), and higher for
      children reporting adequate family-centered care (OR 1.41, 95% CI, 1.14-1.74).
      CONCLUSIONS: Parental receipt of developmental questionnaires is low and varies
      by type of insurance, type of place for usual source of care, and adequacy of
      family-centered care. There is room for improvement in the provision of
      developmental questionnaires and, our results suggest, areas for continuing
      research to understand variations in DA practices.

PMID- 21075322
TI  - Underdiagnosis of pediatric obesity during outpatient preventive care visits.
AB  - OBJECTIVE: To examine obesity diagnosis, obesity-related counseling, and
      laboratory testing rates among obese pediatric patients seen in US preventive
      outpatient visits and to determine patient, provider, and practice-level factors
      that are associated with obesity diagnosis. METHODS: By using 2005-2007 National
      Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care
      Survey data, outpatient preventive visits made by obese (body mass index >=95%) 2
      to 18-year-old patients were examined for frequencies of obesity diagnosis,
      diet, exercise, or weight reduction counseling, and glucose or cholesterol
      testing. Multivariable logistic regression was used to examine whether patient
      level (gender, age, race/ethnicity, insurance type) and provider/practice-level
      (geographic region, provider specialty, and practice setting) factors were
      associated with physician obesity diagnosis. RESULTS: Physicians documented an
      obesity diagnosis in 18% (95% confidence interval, 13-23) of visits made by 2- to
      18-year-old patients with a body mass index >=95%. Documentation of an obesity
      diagnosis was more likely for non-white patients (odds ratio 2.87; 95% confidence
      interval, 1.3-6.3). Physicians were more likely to provide obesity-related
      counseling (51% of visits) than to conduct laboratory testing (10% of visits) for
      obese pediatric patients. CONCLUSION: Rates of documented obesity diagnosis,
      obesity-related counseling, and laboratory testing for comorbid conditions among
      obese pediatric patients seen in US outpatient preventive visits are suboptimal.
      Efforts should target enhanced obesity diagnosis as a first step toward improving
      pediatric obesity management.

PMID- 21075323
TI  - Association of adolescent choking game activity with selected risk behaviors.
AB  - OBJECTIVE: Previous research has recommended education for parents, teachers, and
      anticipatory guidance by pediatricians regarding participation in the so-called
      choking game, a potentially fatal behavior. The purpose of this study was to
      examine possible associations between selected demographic variables and risk
      behaviors with youth engagement in the choking game on the basis of secondary
      data analysis from a general adolescent health risk behavior survey. METHODS:
      Self-administered survey data from an adolescent needs assessment was used to
      assess choking game behavior between fall 2008 and fall 2009. The sample included
      192 classrooms across 88 schools in a Midwestern state. RESULTS: Of the 3598
      questionnaires distributed to middle and high school students, 3408 (95%) were
      returned completed. Participation rate in the choking game was 9%, with male
      participation (11%) greater than female participation (7%), and high school
      students (11%) more likely than middle school students (5%) to participate.
      Adjusted odds ratios found that the likelihood of middle school students engaging
      in the choking game were higher for older students, substance users, and those
      having lower grades. For high school students, adjusted odds ratios found that
      being older, substance use, and selected mental health issues (forced sex and
      attempted suicide) were most associated with choking activities. CONCLUSIONS:
      Engaging in the choking game was highly associated with abuse of substances,
      suggesting that youth engage in the choking game for the thrill-seeking
      experience of brief euphoria, a drug-related feeling. To reduce the potentially
      fatal consequences associated with this behavior, pediatricians should screen
      youths and provide anticipatory guidance for higher-risk youths and their
      parents.

PMID- 21075325
TI  - Progress in molecular biology and translational science. Preface.

PMID- 21075324
TI  - Identifying children with lifelong chronic conditions for care coordination by
      using hospital discharge data.
AB  - BACKGROUND: Children with lifelong chronic conditions (LLCC) are costly, of low
      prevalence, and a high proportion of patients at children's hospitals. Few
      methods identify these patients. OBJECTIVES: We sought to identify children with
      LLCC in hospital discharge data for care coordination by using clinical risk
      groups (CRGs), to evaluate the accuracy of this methodology compared with a chart
      review and to investigate accuracy according to condition groups. METHODS: CRG
      software identified LLCC children who receive care at a primary care clinic,
      Odessa Brown Children's Clinic, by using Seattle Children's Hospital discharge
      data. RESULTS: There were 5356 active Odessa Brown Children's Clinic patients
      with at least 1 clinic encounter in 2006-2007. Six hundred two (11.2%) patients
      were admitted to Seattle Children's Hospital, and 1703 (31.8%) were seen only in
      the emergency department over 7 years (2001-2007). One hundred sixty-four (7%)
      were identified to have a LLCC. In a blind review of 200 (33.2%) children with
      inpatient encounters, the specificity of the CRG designation to LLCC was 95.0%
      (95% confidence interval [CI], 90.0%-98.0%), sensitivity 76.3% (95% CI, 63.4%
      86.4%). Mental health conditions formed the largest group that was chart-review
      positive and CRG negative (7 of 14). Children hospitalized before 13 months of
      age were the second largest group (3 of 14). Clinical review placed the 164
      patients in these condition groups: sickle cell disease, 43 (26.2%),
      neurological, 37 (22.6%), mental health, 22 (13.4%), malignancies, 4 (2.4%),
      other 52 (31.7%), and no chronic condition 6 (3.7%). CONCLUSION: This study
      demonstrates a unique way to identify children with LLCC for care coordination by
      using hospital administrative data.

PMID- 21075326
TI  - Introduction to the molecular biology of cancer: translation to the clinic.

PMID- 21075327
TI  - Molecular biology and anticancer drug discovery.
AB  - The profound impact of molecular biology on the philosophy of how one should seek
      new cancer therapeutics cannot be overstated. It has enabled the discovery of
      unique drugs as well as the identification of new drug targets and biomarkers and
      the creation of powerful animal models. Nevertheless, the process of cancer drug
      discovery remains inherently complex and inefficient. This is partially a
      consequence of the requirement of any successful therapy to show differential
      effects toward tumor cells relative to nonmalignant cells. The goal of this
      chapter is to outline the impact of molecular biology on modern approaches to
      anticancer drug discovery and to highlight the continuing challenges.

PMID- 21075329
TI  - Chromosomal aberrations in solid tumors.
AB  - Ever since the identification of the exact number of human chromosomes in 1956,
      several cancer-specific chromosomal abnormalities have been identified in
      different tumors. Among the various genetic changes, such as alterations in
      oncogenes, tumor suppressor genes, and microRNA genes, recurrent chromosome
      translocations have been identified as an important class of mutations in
      hematological malignancies, soft tissue sarcomas, and more recently in prostate
      cancer and lung cancer. Recurrent gene fusions are used for cancer classification
      and as diagnostic markers, and some have been successfully targeted for drug
      development. Recent advances in high-throughput sequencing technology and the
      ambitious undertaking of "The Cancer Genome Atlas" (TCGA) project will help drive
      the identification of the underlying genetic aberrations in most of the solid
      cancers. This chapter presents an overview on the current status of the knowledge
      on chromosome aberrations in solid cancers, cytogenetic and noncytogenetic
      methods for the characterization of changes at the DNA and RNA levels,
      technological advancements in high-throughput characterization of the cancer
      genome and transcriptome, and the current understanding of the molecular
      mechanism involved in the formation of gene fusions in solid cancer.

PMID- 21075330
TI  - Circulating tumor cells.
AB  - Circulating tumor cells (CTCs) can be separated and characterized from normal
      hematopoietic cellular constituents by a variety of methods. Different strategies
      have included separation by physical characteristics, such as size or weight, or
      by biological characteristics, such as expression of epithelial or cancer
      specific markers. Of the latter, rtPCR for epithelial-related gene message, such
      as cytokeratin, and immunoseparation techniques using monoclonal antibodies
      against epithelial cellular adhesion molecule, have gained the most widespread
      use in investigational and standard clinical application to date. Detection and
      monitoring of CTCs might be useful for screening, prognosis, prediction of
      response to therapy, or monitoring clinical course in patients with primary or
      metastatic cancer. Currently, monitoring patients with metastatic disease is the
      most practical application of CTCs. In this regard, several studies have
      demonstrated that approximately 50-70% of patients with metastatic breast, colon,
      and prostate cancers have elevated CTC levels, when evaluated using a highly
      automated immunomagnetic CTC assay system, designated CellSearch(r). These
      studies demonstrate that elevated CTC levels prior to initiation of a new
      systemic therapy are associated with a worse prognosis than those that do not,
      and that persistently elevated or subsequent rising CTC levels strongly suggest
      that the therapeutic regimen with which the patient is being treated is not
      working. Similar results have been shown with rtPCR assays, although they are not
      as widely available for routine clinical use. New areas of research are directed
      toward developing more sensitive means of CTC detection and generating a variety
      of methods to characterize the molecular and biologic nature of CTCs, such as the
      status of hormone receptors, epidermal, and other growth factor receptor family
      members, and indications of stem-cell characteristics.

PMID- 21075328
TI  - Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of
      cancer molecular biology to the clinic.
AB  - Chemokines are a family of small and secreted proteins that play pleiotropic
      roles in inflammation-related pathological diseases, including cancer. Among the
      identified 50 human chemokines, chemokine (C-C motif) ligand 2 (CCL2) is of
      particular importance in cancer development since it serves as one of the key
      mediators of interactions between tumor and host cells. CCL2 is produced by
      cancer cells and multiple different host cells within the tumor microenvironment.
      CCL2 mediates tumorigenesis in many different cancer types. For example, CCL2 has
      been reported to promote prostate cancer cell proliferation, migration, invasion,
      and survival, via binding to its functional receptor CCR2. Furthermore, CCL2
      induces the recruitment of macrophages and induces angiogenesis and matrix
      remodeling. Targeting CCL2 has been demonstrated as an effective therapeutic
      approach in preclinical prostate cancer models, and currently, neutralizing
      monoclonal antibody against CCL2 has entered into clinical trials in prostate
      cancer. In this chapter, targeting CCL2 in prostate cancer will be used as an
      example to show translation of laboratory findings from cancer molecular biology
      to the clinic.

PMID- 21075331
TI  - Stem cells in normal development and cancer.
AB  - In this chapter we provide an overview of stem cells in normal tissues as well as
      in many different types of cancers. All tissues in the body are derived from
      organ-specific stem cells that retain the ability to self-renew and differentiate
      into specific cell types. The cancer stem cell hypothesis suggests that tumors
      arise from cell populations with dysregulated self-renewal. This may be tissue
      stem cells or more differentiated cells that acquire self-renewal capabilities.
      In addition, we outline some useful assays for purification and isolation of
      cancer stem cells including the dye exclusion side population assay, flow
      cytometry sorting techniques for identification of putative cancer stem cell
      markers, tumorspheres assay, aldehyde dehydrogenase activity assay, PKH, and
      other membrane staining used to label the cancer stem cells, as well as in vivo
      xenograft transplantation assays. We also examine some of the cell signaling
      pathways that regulate stem cell self-renewal including the Notch, Hedgehog,
      HER2/PI3K/Akt/PTEN, and p53 pathways. We also review information demonstrating
      the involvement of the microenvironment or stem cell niche and its effects on the
      growth and maintenance of cancer stem cells. Finally, we highlight the
      therapeutic implications of targeting stem cells by inhibiting these pathways for
      the treatment and prevention of cancer.

PMID- 21075332
TI  - Bioinformatics and systems biology of cancers.
AB  - Molecular databases and bioinformatics methods and tools are essential for modern
      cancer research. Multilevel analyses of all the protein-coding genes, thousands
      of proteins, and hundreds of metabolites require integration in terms of
      signaling and metabolic pathways and networks. This chapter provides background
      and examples of genomic, gene expression, epigenomic, proteomic, and metabolomic
      investigations of cancer progression and emergence of invasive and metastatic
      properties of cancers.

PMID- 21075333
TI  - Progress in cancer nanotechnology.

PMID- 21075335
TI  - Cancer epigenetics.
AB  - Epigenetic studies reveal important insights into cancer biology. This chapter
      presents a broad picture of how epigenetic changes in health and disease and in
      response to environment contribute to carcinogenesis, and how findings from newer
      approaches and emergent technologies may extend these observations. Consideration
      is given to biological insights drawn from studies of epigenomic patterns in
      cancer cells, and the influence of epigenomic profiling on diagnosis, therapy,
      and prognosis. The chapter begins with a brief overview of the concepts and
      foundations on which epigenetics is built and concludes with comments on
      prospects for the future of cancer epigenetics.

PMID- 21075336
TI  - Molecular targets and clinical cancer risk reductive interventions.

PMID- 21075337
TI  - The development of the alimentary tract and its associated organs. Preface.

PMID- 21075338
TI  - Formation of the murine endoderm: lessons from the mouse, frog, fish, and chick.
AB  - The mammalian definitive endoderm arises as a simple epithelial sheet. This sheet
      of cells will eventually produce the innermost tube that comprises the entire
      digestive tract from the esophagus to the colon as well as the epithelial
      component of the digestive and respiratory organs including the thymus, thyroid,
      lung, liver, gallbladder, and pancreas. Thus a wide array of tissue types are
      derived from the early endodermal sheet, and understanding the morphological and
      molecular mechanisms used to produce this tissue is integral to understanding the
      development of all these organs. The goal of this chapter is to summarize what is
      known about the morphological and molecular mechanisms used to produce this
      embryonic germ layer. Although this chapter mainly focuses on the mechanisms used
      to generate the murine endoderm, supportive or suggestive data from other
      species, including chick, frog (Xenopus laevis), and the Zebrafish (Danio rerio)
      are also examined.

PMID- 21075339
TI  - Dividing the tubular gut: generation of organ boundaries at the pylorus.
AB  - The discrete organs that comprise the gastrointestinal tract (esophagus, stomach,
      small intestine, and large intestine) arise embryonically by regional
      differentiation of a single tube that is initially morphologically similar along
      its length. Regional organ differentiation programs, for example, for stomach or
      intestine, involve signaling cross-talk between epithelium and mesenchyme and
      result in the formation of precise boundaries between organs, across which
      dramatic differences in both morphology and gene expression are seen. The pylorus
      is a unique area of the gut tube because it not only marks an important organ
      boundary in the tubular gut (the stomach/intestinal boundary) but is also the hub
      for the development of multiple accessory organs (liver, pancreas, gall bladder,
      and spleen). This chapter examines: (a) our current understanding of the
      molecular and morphogenic processes that underlie the generation of the dramatic
      epithelial tissue boundary that compartmentalizes stomach and intestine; (b) the
      tissue interactions that promote development of the accessory organs in this
      area; and (c) the molecular interactions that specify patterning of the pyloric
      sphincter. Though the focus here is primarily on the mouse as a model organism,
      the molecular underpinnings of organ patterning near the pylorus are shared by
      chick and frog. Thus, further study of these conserved developmental programs
      could potentially shed light on the mechanisms underlying human pyloric
      malformations such as infantile hypertrophic pyloric stenosis.

PMID- 21075340
TI  - Molecular determinants of metaplastic and neoplastic transformation in the
      esophageal epithelium.
AB  - A metaplastic change where normal squamous mucosa of the esophagus is replaced by
      columnar mucosa is considered an adaptive process to withstand the chronic
      gastroesophageal reflux injury. However, this phenotypic switch in the esophageal
      mucosa is associated with an increased propensity to undergo neoplastic
      transformation. In this chapter, we review the molecular alterations that are
      relevant to metaplastic and neoplastic transformations in the esophagus and also
      discuss the mechanisms that could potentially contribute to this transformation.

PMID- 21075341
TI  - The gastric mucosa development and differentiation.
AB  - The development and differentiation of the gastric mucosa are controlled by a
      complex interplay of signaling proteins and transcriptional regulators. This
      process is complicated by the fact that the stomach is derived from two germ
      layers, the endoderm and the mesoderm, with the first giving rise to the mature
      epithelium and the latter contributing the smooth muscle required for
      peristalsis. Reciprocal epithelial-mesenchymal interactions dictate the formation
      of the stomach during fetal development, and also contribute to its continuous
      regeneration and differentiation throughout adult life. In this chapter, we
      discuss the discoveries that have been made in different model systems, from
      zebrafish to human, which show that the Hedgehog, Wnt, Notch, bone morphogenetic
      protein, and fibroblast growth factor (FGF) signaling systems play essential
      roles during various stages of stomach development.

PMID- 21075334
TI  - Applications of molecular imaging.
AB  - Today molecular imaging technologies play a central role in clinical oncology.
      The use of imaging techniques in early cancer detection, treatment response, and
      new therapy development is steadily growing and has already significantly
      impacted on clinical management of cancer. In this chapter, we overview three
      different molecular imaging technologies used for the understanding of disease
      biomarkers, drug development, or monitoring therapeutic outcome. They are (1)
      optical imaging (bioluminescence and fluorescence imaging), (2) magnetic
      resonance imaging (MRI), and (3) nuclear imaging (e.g., single-photon emission
      computed tomography (SPECT) and positron emission tomography (PET)). We review
      the use of molecular reporters of biological processes (e.g., apoptosis and
      protein kinase activity) for high-throughput drug screening and new cancer
      therapies, diffusion MRI as a biomarker for early treatment response and PET and
      SPECT radioligands in oncology.

PMID- 21075343
TI  - Hedgehog signaling in gastric physiology and cancer.
AB  - The Hedgehog family of ligands was originally identified in mutagenesis screens
      of Drosophila embryos. Hedgehog signaling in multiple tissues is important during
      embryonic development. A common theme regarding Hedgehog expression in adult
      tissues is that tissue injury reactivates the developmental pattern of
      expression. In most instances, this appears to be important to initiate tissue
      repair. In the gastrointestinal (GI) tract, where epithelial cells are constantly
      replenished from progenitor populations, Hedgehog signaling also appears to be
      essential for regeneration. By contrast, reactivated Hedgehog signaling in adult
      tissues does not automatically predispose the tissue to transformation, but
      instead requires sustained tissue injury in the form of chronic inflammation. In
      this chapter, we review what is known about Hedgehog ligands and signaling during
      development of relevant organs, and discuss how the patterns of Hedgehog
      regulation are recapitulated in the GI tract during embryogenesis, adult
      homeostasis, and neoplastic transformation.

PMID- 21075342
TI  - Oxyntic atrophy, metaplasia, and gastric cancer.
AB  - Gastric carcinogenesis involves the loss of parietal cells (oxyntic atrophy) and
      subsequent replacement of the normal gastric lineages with metaplastic cells. In
      humans, two metaplastic lineages develop as sequelae of chronic Helicobacter
      pylori infection: intestinal metaplasia and spasmolytic polypeptide-expressing
      metaplasia (SPEM). Mouse models of both chronic Helicobacter infection and acute
      pharmacological oxyntic atrophy have led to the discovery that SPEM arises from
      transdifferentiation of mature chief cells. The presence of inflammation promotes
      the expansion of SPEM in mice. Furthermore, studies in Mongolian gerbils as well
      as increasing evidence from human studies indicate that SPEM likely represents a
      precursor for the development of intestinal metaplasia. These findings suggest
      that loss of parietal cells, augmented by chronic inflammation, leads to a
      cascade of metaplastic events. Identification of specific biomarkers for SPEM and
      intestinal metaplasia hold promise for providing both early detection of
      preneoplasia and information on prognostic outcome following curative resection.

PMID- 21075345
TI  - The role of the basement membrane as a modulator of intestinal epithelial
      mesenchymal interactions.
AB  - Intestinal development is a process of continuous dynamic bidirectional crosstalk
      between epithelial and underlying mesenchymal cells. This crosstalk is mediated
      by well-dissected signaling pathways. Another crucial actor in the epithelio
      mesenchymal interactions is the stromal microenvironment, which is composed of
      extracellular matrix molecules. Among them, the basement membrane (BM) molecules
      are secreted by the epithelium and mesenchyme in a complementary manner. These
      molecules signal back to the cells via the integrins or other specific receptors.
      In this review, we mainly focus on the BM molecules, particularly laminins. The
      major BM molecules are organized in a complex molecular network, which is highly
      variable among organs. Cell culture, coculture, and grafting models have been of
      great interest in understanding the importance of these molecules. Mouse gene
      ablation of laminin chains are interesting models, which often lead to embryonic
      death and are frequently accompanied by compensatory processes. Overall, the BM
      molecules have a crucial role in the careful maintenance of intestinal
      homeostasis.

PMID- 21075344
TI  - The intestinal stem cell.
AB  - The intestinal epithelium is one of the most rapidly proliferating organs in the
      body. A complete turnover of the epithelium occurs every 3-5 days in the mouse, a
      process that is maintained by a small population of intestinal stem cells (ISCs)
      that reside in the crypt bases. The signals that regulate the behavior of these
      ISCs are still unknown. This has been due, until recently, to the singular lack
      of definitive ISC markers. The recent identification of genes that mark
      functional stem cells has yielded insights into how ISCs are regulated and
      maintained by their surrounding niche. Herein, we examine the body of literature
      regarding the precise identity and location of the ISCs, the role of the
      surrounding niche in ISC maintenance and regulation, as well as the hypothesis
      that the ISCs are the cells of origin in colorectal cancer.

PMID- 21075346
TI  - Regulation of gene expression in the intestinal epithelium.
AB  - Regulation of gene expression within the intestinal epithelium is complex and
      controlled by various signaling pathways that regulate the balance between
      proliferation and differentiation. Proliferation is required both to grow and to
      replace cells lost through apoptosis and attrition, yet in all but a few cells,
      differentiation must take place to prevent uncontrolled growth (cancer) and to
      provide essential functions. In this chapter, we review the major signaling
      pathways underlying regulation of gene expression within the intestinal
      epithelium, based primarily on data from mouse models, as well as specific
      morphogens and transcription factor families that have a major role in regulating
      intestinal gene expression, including the Hedgehog family, Forkhead Box (FOX)
      factors, Homeobox (HOX) genes, ParaHox genes, GATA transcription factors,
      canonical Wnt/beta-catenin signaling, EPH/Ephrins, Sox9, BMP signaling,
      PTEN/PI3K, LKB1, K-RAS, Notch pathway, HNF, and MATH1. We also briefly highlight
      important emerging areas of gene regulation, including microRNA (miRNA) and
      epigenetic regulation.

PMID- 21075348
TI  - HIV-1 Vpu disarms natural killer cells.
AB  - Natural killer (NK)-cell killing of virus-infected cells is regulated in part by
      the engagement of activation and coactivation receptors. In this issue of Cell
      Host & Microbe, Shah et al. (2010) demonstrate that HIV-1 protects infected cells
      from NK-cell-mediated killing by hindering NK-cell degranulation through
      downmodulation of NTB-A coactivation receptor ligands by the Vpu accessory
      protein.

PMID- 21075349
TI  - Caging targets for destruction.
AB  - Intracellular bacterial pathogens engage in a tug-of-war with innate host
      defenses. In this issue of Cell Host & Microbe, Mostowy et al. (2010) identify a
      role for the septin family of cytoskeletal proteins in targeting intracellular
      Shigella to the autophagy pathway.

PMID- 21075350
TI  - Anthrax toxin delivers a one-two punch.
AB  - Although anthrax toxin was identified as a major Bacillus anthracis virulence
      factor over 50 years ago, defining the physiologically relevant targets has been
      challenging. Liu et al. demonstrate that intoxication of myeloid-derived cells
      contributes to establishing infection but is not required for mortality resulting
      from high toxin concentrations associated with end-stage disease.

PMID- 21075347
TI  - Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia.
AB  - Intestinal metaplasia (IM) is a biologically interesting and clinically relevant
      condition in which one differentiated type of epithelium is replaced by another
      that is morphologically similar to normal intestinal epithelium. Two classic
      examples of this are gastric IM and Barrett's esophagus (BE). In both, a chronic
      inflammatory microenvironment, provoked either by Helicobacter pylori infection
      of the stomach or acid and bile reflux into the esophagus, precedes the
      metaplasia. The Caudal-related homeodomain transcription factors Cdx1 and Cdx2
      are critical regulators of the normal intestinal epithelial cell phenotype.
      Ectopic expression of Cdx1 and Cdx2 occurs in both gastric IM as well as in BE.
      This expression precedes the onset of the metaplasia and implies a causal role
      for these factors in this process. We review the observations regarding the role
      of chronic inflammation and the Cdx transcription factors in the pathogenesis of
      gastric IM and BE.

PMID- 21075351
TI  - Degranulation of natural killer cells following interaction with HIV-1-infected
      cells is hindered by downmodulation of NTB-A by Vpu.
AB  - Natural killer (NK) cell degranulation in response to virus-infected cells is
      triggered by interactions between invariant NK cell surface receptors and their
      ligands on target cells. Although HIV-1 Vpr induces expression of ligands for NK
      cell activation receptor, NKG2D, on infected cells, this is not sufficient to
      promote lytic granule release. We show that triggering the NK cell coactivation
      receptor NK-T- and -B cell antigen (NTB-A) alongside NKG2D promotes NK cell
      degranulation. Normally, NK cell surface NTB-A binds to NTB-A on CD4+ T cells.
      However, HIV-1 Vpu downmodulates NTB-A on infected T cells. Vpu associates with
      NTB-A through its transmembrane region without promoting NTB-A degradation. Cells
      infected with HIV-1 Vpu mutant elicited at least 50% more NK cells to degranulate
      than wild-type virus. Moreover, NK cells have a higher capacity to lyse HIV
      infected cells with a mutant Vpu. Thus, Vpu downmodulation of NTB-A protects the
      infected cell from lysis by NK cells.

PMID- 21075352
TI  - Mouse STAT2 restricts early dengue virus replication.
AB  - Dengue virus encodes several interferon antagonists. Among these the NS5 protein
      binds STAT2, a necessary component of the type I interferon signaling pathway,
      and targets it for degradation. We now demonstrate that the ability of dengue NS5
      to associate with and degrade STAT2 is species specific. Thus, NS5 is able to
      bind and degrade human STAT2, but not mouse STAT2. This difference was exploited
      to demonstrate, absent manipulation of the viral genome, that NS5-mediated IFN
      antagonism is essential for efficient virus replication. Moreover, we demonstrate
      that differences in NS5 mediated binding and degradation between human and mouse
      STAT2 maps to a region within the STAT2 coiled-coil domain. By using STAT2(-/-)
      mice, we also demonstrate that mouse STAT2 restricts early dengue virus
      replication in vivo. These results suggest that overcoming this restriction
      through transgenic mouse technology may help in the development of a long-sought
      immune-competent mouse model of dengue virus infection.

PMID- 21075353
TI  - Dengue virus-induced autophagy regulates lipid metabolism.
AB  - Autophagy influences numerous cellular processes, including innate and adaptive
      immunity against intracellular pathogens. However, some viruses, including dengue
      virus (DENV), usurp autophagy to enhance their replication. The mechanism for a
      positive role of autophagy in DENV infection is unclear. We present data that
      DENV induction of autophagy regulates cellular lipid metabolism. DENV infection
      leads to an autophagy-dependent processing of lipid droplets and triglycerides to
      release free fatty acids. This results in an increase in cellular beta-oxidation,
      which generates ATP. These processes are required for efficient DENV replication.
      Importantly, exogenous fatty acids can supplant the requirement of autophagy in
      DENV replication. These results define a role for autophagy in DENV infection and
      provide a mechanism by which viruses can alter cellular lipid metabolism to
      promote their replication.

PMID- 21075354
TI  - Entrapment of intracytosolic bacteria by septin cage-like structures.
AB  - Actin-based motility is used by various pathogens for dissemination within and
      between cells. Yet host factors restricting this process have not been
      identified. Septins are GTP-binding proteins that assemble as filaments and are
      essential for cell division. However, their role during interphase has remained
      elusive. Here, we report that septin assemblies are recruited to different
      bacteria that polymerize actin. We observed that intracytosolic Shigella either
      become compartmentalized in septin cage-like structures or form actin tails.
      Inactivation of septin caging increases the number of Shigella with actin tails
      and enhances cell-to-cell spread. TNF-alpha, a host cytokine produced upon
      Shigella infection, stimulates septin caging and restricts actin tail formation
      and cell-to-cell spread. Finally, we show that septin cages entrap bacteria
      targeted to autophagy. Together, these results reveal an unsuspected mechanism of
      host defense that restricts dissemination of invasive pathogens.

PMID- 21075357
TI  - The reliability of and the relation between non-symbolic numerical distance
      effects in comparison, same-different judgments and priming.
AB  - The development of number processing is generally studied by examining the
      performance on basic number tasks (comparison task, same-different judgment, and
      priming task). Using these tasks, so-called numerical distance effects are
      obtained. All these effects are generally explained by assuming a magnitude
      representation related to a mental number line: magnitudes are represented from
      left to right with partially overlapping representations for nearby numbers. In
      this study, we compared the performance of adults on these different tasks using
      non-symbolic stimuli. First, we investigated whether the effects obtained in
      these behavioral tasks are reliable. Second, we examined the relation between the
      three different effects. The results showed that the observed effects in the case
      of the comparison task and the same-different task proved to be reliable. The
      numerical distance effect obtained in the priming task, however, was not
      reliable. In addition, a correlation was found between the distance effects in
      the comparison task and the same-different task. The priming distance effect did
      not correlate with the other two effects. These results suggest important
      differences between distance effects obtained under automatic and intentional
      task instructions regarding the use of them as indices of mathematical ability.

PMID- 21075355
TI  - Statins enhance formation of phagocyte extracellular traps.
AB  - Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA)
      reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent clinico
      epidemiologic studies correlate patients receiving statin therapy with having
      reduced mortality associated with severe bacterial infection. Investigating the
      effect of statins on the innate immune capacity of phagocytic cells against the
      human pathogen Staphylococcus aureus, we uncovered a beneficial effect of statins
      on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis
      and oxidative burst were inhibited. Probing instead for an extracellular
      mechanism of killing, we found that statins boosted the production of
      antibacterial DNA-based extracellular traps (ETs) by human and murine neutrophils
      and also monocytes/macrophages. The effect of statins to induce phagocyte ETs was
      linked to sterol pathway inhibition. We conclude that a drug therapy taken
      chronically by millions alters the functional behavior of phagocytic cells, which
      could have ramifications for susceptibility and response to bacterial infections
      in these patients.

PMID- 21075358
TI  - Dissociations between identity and location negative priming.
AB  - Negative priming refers to the phenomenon of a slowed response time to a
      previously ignored distractor. Identity negative priming can be observed when the
      identity of a previous distractor is repeated as the target identity, and
      location negative priming can be observed when the spatial location of a previous
      distractor is repeated as the target location. This article reviewed and
      integrated previous findings and provided empirical evidence to show the
      dissociations between location and identity negative priming: (a) the removal of
      probe distractor impeded identity negative priming but not location negative
      priming; (b) identity negative priming was modulated by the distance between the
      target and distractor, while location negative priming was not; and (c)
      perceptual grouping of the target and distractor affected identity negative
      priming but not location negative priming.

PMID- 21075356
TI  - Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential
      for establishment of Bacillus anthracis infections in mice.
AB  - Bacillus anthracis kills through a combination of bacterial infection and
      toxemia. Anthrax toxin working via the CMG2 receptor mediates lethality late in
      infection, but its roles early in infection remain unclear. We generated myeloid
      lineage specific CMG2-deficient mice to examine the roles of macrophages,
      neutrophils, and other myeloid cells in anthrax pathogenesis. Macrophages and
      neutrophils isolated from these mice were resistant to anthrax toxin. However,
      the myeloid-specific CMG2-deficient mice remained fully sensitive to both anthrax
      lethal and edema toxins, demonstrating that targeting of myeloid cells is not
      responsible for anthrax toxin-induced lethality. Surprisingly, the myeloid
      specific CMG2-deficient mice were completely resistant to B. anthracis infection.
      Neutrophil depletion experiments suggest that B. anthracis relies on anthrax
      toxin secretion to evade the scavenging functions of neutrophils to successfully
      establish infection. This work demonstrates that anthrax toxin uptake through
      CMG2 and the resulting impairment of myeloid cells are essential to anthrax
      infection.

PMID- 21075359
TI  - Expression of ghrelin in human salivary glands and its levels in saliva and serum
      in Chinese obese children and adolescents.
AB  - OBJECTIVE: The aim of the present study was to reveal the expression
      characteristics of ghrelin in human three major salivary glands and to
      investigate saliva and serum ghrelin level and the relation with weight and lipid
      indices in Chinese children. DESIGN: Expression and distribution of ghrelin in
      parotid, submandibular, and sublingual glands were measured by reverse
      transcription-polymerase chain reaction and immunohistochemistry. Saliva and
      serum samples were collected from 194 Chinese children and adolescents (mean age
      12.98 years). Ghrelin levels were tested by enzyme-linked immunosorbent assay.
      Significant differences were estimated by one-way ANOVA. RESULTS: Ghrelin mRNA
      was expressed in parotid and submandibular glands, but was not detectable in
      sublingual glands. Ghrelin proteins were widespread in the cytoplasm of striated,
      intercalated and excretory ducts, as well as in serous acini of parotid and
      submandibular glands, but not in mucous acinar cells of sublingual glands. Saliva
      and serum ghrelin levels were increased along with BMI. There was positive
      correlation between saliva and serum ghrelin levels (r=0.534, P<0.01). Serum and
      saliva ghrelin levels were both significantly correlated with BMI (r=0.523,
      r=0.374, P<0.01, respectively), but not with blood lipid levels. CONCLUSIONS:
      Parotid and submandibular glands were primary sources of ghrelin produced and
      released in saliva. Although whether salivary ghrelin could be useful in the
      diagnosis of obesity remains to be determined, salivary ghrelin might be a
      possible alternative to serum ghrelin for predicting obesity.

PMID- 21075360
TI  - Kinetic study of acid depolymerization of chitosan and effects of low molecular
      weight chitosan on erythrocyte rouleaux formation.
AB  - In this study, the depolymerization of chitosan was carried out in an acetic acid
      aqueous solution and was followed by viscometry for molecular weight
      determination. It was found that the depolymerization rate increased with
      elevated temperatures and with high acid concentrations. Based on FTIR analysis,
      the chitosan was depolymerized randomly along the backbone; no other structural
      change was observed during the acid depolymerization process. Revealed in the TGA
      study, the degradation temperature and char yield of LMWCs (low molecular weight
      chitosan) were molecular weight dependent. The blood compatibility of LMWCs was
      also investigated: rouleaux formation was observed when erythrocyte contacted
      with LMWCs, which showed that LMWCs are able to interfere with the negatively
      charged cell membrane through its polycationic properties. Furthermore, as
      regards a kinetics investigation, the values of M(n) (number-average molecular
      weight) were obtained from an experimentally determined relationship. The
      kinetics study showed that the complex salt, formed by amine on chitosan and
      acetic acid, acted as catalyst. Finally, the activation energy for the hydrolysis
      of the glycosidic linkage on chitosan was calculated to be 40kJ/mol; the
      mechanism of acid depolymerization is proposed. In summary, LMWCs could be easily
      and numerously generated with acid depolymerization for further biological
      applications.

PMID- 21075361
TI  - Carbohydrate-mediated inhibition of ice recrystallization in cryopreserved human
      umbilical cord blood.
AB  - Cryopreservation of human umbilical cord blood (UCB) typically involves the
      cryoprotectant dimethylsulfoxide (DMSO), however, infusional toxicity and
      reductions in cell viability remain a concern. Ice recrystallization (IR) is an
      important source of cryopreservation-induced cellular injury and limits the stem
      cell dose in UCB units. Carbohydrates have wide-ranging intrinsic IR inhibition
      (IRI) activity related to structural properties. We investigated the impact of
      carbohydrate IRI on cell viability, induction of apoptosis and hematopoietic
      progenitor function in cryopreserved UCB. Mononuclear cells (MNCs) from UCB were
      cryopreserved in storage media containing specific carbohydrates (200mM) and
      compared to 5% DMSO. Samples were analyzed under conditions of high IR ('slow'
      thaw) and low IR ('fast' thaw). Thawed samples were analyzed for viability and
      apoptosis by flow cytometry and hematopoietic function using colony-forming unit
      (CFU) assays. IRI of carbohydrate solutions was determined using the 'splat
      cooling' assay. Greater IRI capacity of carbohydrates correlated with increased
      yield of viable MNCs (r(2)=0.92, p=0.004) and CD34(+) cells (r(2)=0.96, p=0.019)
      after thawing under conditions of high IR. The correlations were less apparent
      under conditions of low IR. Carbohydrates with greater IRI modulate the induction
      of early apoptosis during thawing, especially in CD34+ cells (r(2)=0.96,
      p=0.0001) as compared to total mononuclear cells (p=0.006), and preserve CFU
      capacity in vitro (r(2)=0.92, p=<0.0001). Our results suggest that carbohydrates
      with potent IRI increase the yield of non-apoptotic and functional hematopoietic
      progenitors and provide a foundation for the development of novel synthetic
      carbohydrates with enhanced IRI properties to improve cryopreservation of UCB.

PMID- 21075362
TI  - A framework for diagnosis of urinary incontinence disease based on scoring
      measures and automatic classifiers.
AB  - This work develops a decision support system based on machine learning and
      scoring measures to determine the type of urinary incontinence in women with low
      urinary tract symptoms. This system has two main branches. The former consists of
      selecting the feature set which best defines the UI type from the set of features
      (age, weight, etc.) characterizing a patient. This feature set is computed from
      several scoring measures. The patients characterized by the optimum feature set
      are then classified according to C4.5 and SVM classifiers. The results are
      evaluated according to Sensitivity and Specificity evaluation measures. The
      management of the final system is simple and its performance is high, getting
      Sensitivities over 80% and Specificities near 100% for some configurations.

PMID- 21075363
TI  - Reduced recognition of fear and sadness in post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is associated with impairments in emotional
      experience and expression. The current study examined the recognition of
      emotional facial expressions in PTSD patients and matched healthy controls, both
      in terms of accuracy and sensitivity. The task involved short video clips of a
      neutral face changing (morphing) into one of the six basic emotions (happiness,
      anger, fear, surprise, disgust and sadness). Clips differed in length, with short
      clips terminating at 20% of maximum emotional intensity, and the longest ones
      ending with a full-blown expression. We observed a specific impairment in the
      PTSD group for recognizing the emotions fear and sadness. This result was
      observed via a reduced accuracy and a decreased sensitivity for these emotions.
      We discuss the observed altered affective processing and its possible clinical
      implications.

PMID- 21075364
TI  - Dissolved silver in the Baltic Sea.
AB  - The increased use of silver as a biocide in nanoparticle formulations has
      heightened concern on possible environmental implications owing to its toxicity.
      There is however very little data on the concentration levels of silver in marine
      and freshwaters. Here, I report data on dissolved (<0.4 MUm filter) silver
      concentration in the surface waters of the Baltic Sea, the first such data
      reported for a European coastal water body. Levels of dissolved silver in the
      Baltic are comparable to those reported for other American estuarine waters and
      range from non-detectable in the open Baltic Sea Proper (<1 pM) to 9.4 pM (1
      ng/L) in the Stockholm Archipelago, with a mean of 2.8 pM (0.2 ng/L). Inputs from
      wastewater treatment are clearly discernable and might constitute the main source
      of silver to the Stockholm Archipelago and possibly the Baltic Sea Proper.

PMID- 21075365
TI  - Environmental health indicators and a case study of air pollution in Latin
      American cities.
AB  - Environmental health indicators (EHIs) are applied in a variety of research and
      decision-making settings to gauge the health consequences of environmental
      hazards, to summarize complex information, or to compare policy impacts across
      locations or time periods. While EHIs can provide a useful means of conveying
      information, they also can be misused. Additional research is needed to help
      researchers and policy-makers understand categories of indicators and their
      appropriate application. In this article, we review current frameworks for
      environmental health indicators and discuss the advantages and limitations of
      various forms. A case study EHI system was developed for air pollution and health
      for urban Latin American centers in order to explore how underlying assumptions
      affect indicator results. Sixteen cities were ranked according to five indicators
      that considered: population exposed, children exposed, comparison to health-based
      guidelines, and overall PM(10) levels. Results indicate that although some
      overall patterns in rankings were observed, cities' relative rankings were highly
      dependent on the indicator used. In fact, a city that was ranked best under one
      indicator was ranked worst with another. The sensitivity of rankings, even when
      considering a simple case of a single pollutant, highlights the need for clear
      understanding of EHIs and how they may be affected by underlying assumptions.
      Careful consideration should be given to the purpose, assumptions, and
      limitations of EHIs used individually or in combination in order to minimize
      misinterpretation of their implications and enhance their usefulness.

PMID- 21075366
TI  - Laparoscopic ovarian drilling in polycystic ovary syndrome: efficacy of adjusted
      thermal dose based on ovarian volume.
AB  - OBJECTIVE: To compare reproductive outcome of adjusted thermal dose on the basis
      of ovarian volume versus fixed-puncture dosage in laparoscopic ovarian drilling.
      DESIGN: Randomized controlled trial. SETTING: University Women's Health Center.
      PATIENT(S): One hundred twenty patients with polycystic ovary syndrome and
      clomiphene citrate resistance. INTERVENTION(S): Patients were assigned randomly
      to two groups of 60 women each. Group A received an adjusted thermal dose based
      on ovarian volume with use of a new model for dose calculation (60 J/cm(3) of
      ovarian tissue), and group B received 600 J per ovary through four ovarian holes
      regardless of size. One month afterward, the hormonal profile was reevaluated,
      and second-look laparoscopy was performed in patients who had not conceived by 6
      months to evaluate adnexal adhesions. MAIN OUTCOME MEASURE(S): Ovulation,
      conception, and early abortion rates, cycle rhythm, and adnexal adhesions.
      RESULT(S): More patients resumed regular cycles in group A than in group B (87.9%
      vs. 75.4%). The ovulation and pregnancy rates were significantly higher in group
      A than in group B (81.8% vs. 62.2% and 51.7% vs. 36.8%, respectively). There was
      no significant difference between groups in early miscarriage rate or
      postdrilling adhesions. CONCLUSION(S): Adjusted diathermy dose based on ovarian
      volume for laparoscopic ovarian drilling of polycystic ovary syndrome has a
      better reproductive outcome compared with fixed thermal dosage.

PMID- 21075367
TI  - Expression of oct-4 and c-kit antigens in endometriosis.
AB  - The objective of this study was to test the expression of the oct-4 and c-kit,
      both markers of stem cells, in the ectopic endometrial tissue of endometriotic
      lesions of women with severe endometriosis. Our findings show that ectopic
      epithelial cells express oct-4 and c-kit and this suggests that the ectopic
      endometrium in endometriosis has a stem cell origin and could explain the
      possible progression to ovarian cancer.

PMID- 21075368
TI  - Physician experience in performing embryo transfers may affect outcome.
AB  - The distribution of six physicians' pregnancy rates with cycle and patient
      demographics was investigated for 2,212 transfer cycles. The results indicate
      that when the patient and cycle characteristics are compromised, the level of
      physician experience may determine the outcome of embryo transfers.

PMID- 21075369
TI  - Intrauterine demise due to congenital mesoblastic nephroma in a fetus conceived
      by assisted reproductive technology.
AB  - OBJECTIVE: To report a case of antenatally diagnosed congenital mesoblastic
      nephroma in an assisted reproductive technology (ART) conception. DESIGN: Case
      report. SETTING: Tertiary care university-affiliated hospital. PATIENT(S): Fetus
      of 26-weeks' gestation with antenatally diagnosed large abdominal tumor.
      INTERVENTION(S): ART with transfer of cryopreserved embryo. MAIN OUTCOME
      MEASURE(S): Postmortem examination. RESULT(S): Examination revealed a congenital
      mesoblastic nephroma, mixed classic and cellular type, with marked intratumoral
      hemorrhage and associated hydrops. The marked fetal erythroblastosis was
      suggestive of fetal response to pronounced anemia. Intrauterine demise is
      attributed to fetal intratumoral hemorrhage and early nonimmune hydrops secondary
      to a large congenital mesoblastic nephroma. CONCLUSION(S): This is the third
      reported case of congenital mesoblastic nephroma in an ART conception. Whether
      the association between mesoblastic nephroma and ART is coincidental or causative
      remains to be determined.

PMID- 21075371
TI  - Effect of integrity of the posterior cortex in displaced femoral neck fractures
      on outcome after surgical fixation in young adults.
AB  - AIM: To assess whether disruption of the posterior cortex of intracapsular
      femoral fractures leads to an increased incidence of complications following
      closed reduction and internal fixation by multiple cannulated screws in young
      adults. METHODS: A total of 146 consecutive adult patients with 146 femoral neck
      fractures were treated by closed reduction and internal fixation with parallel
      cannulated screw in inverted triangle or diamond configurations. All enrolled
      patients were divided into three groups: those with a non-displaced femoral neck
      fracture (Garden types I or II), those with a displaced femoral neck fracture
      (Garden types III or IV)but no posterior cortex disruption and those with a
      displaced femoral neck fracture (Garden types III or IV) and a disrupted
      posterior cortex. RESULTS: Based on an average follow-up of 4.76 years (range, 2
      6 years), displaced femoral neck fractures with a disrupted posterior cortex
      demonstrated an increased risk for avascular necrosis of the femoral head,
      shortening, redisplacement and conversion of prosthetic replacement as compared
      with those fractures without posterior cortex disruption (p = 0.002, 0.016, 0.001
      and <0.0001, respectively). CONCLUSIONS: As compared with a femoral neck fracture
      with an intact posterior cortex, a displaced femoral neck fracture with a
      disrupted posterior cortex increases the risk for avascular
      necrosis,redisplacement and shortening and raises the likelihood that prosthetic
      replacement will be needed.Orthopaedic surgeons should be aware of this
      prognostic factor.

PMID- 21075370
TI  - Changes in plasma mullerian-inhibiting substance and brain-derived neurotrophic
      factor after chemotherapy in premenopausal women.
AB  - Eight premenopausal women with cancer had blood drawn for analysis of brain
      derived neurotrophic factor (BDNF) and mullerian-inhibiting substance (MIS)
      before and 3 months after receiving chemotherapy. Unlike MIS, BDNF levels were
      not reduced after chemotherapy.

PMID- 21075372
TI  - Do changes in dynamic plantar pressure distribution, strength capacity and
      postural control after intra-articular calcaneal fracture correlate with clinical
      and radiological outcome?
AB  - Fractures of the calcaneus are often associated with serious permanent
      disability, a considerable reduction in quality of life, and high socio-economic
      cost. Although some studies have already reported changes in plantar pressure
      distribution after calcaneal fracture, no investigation has yet focused on the
      patient's strength and postural control. METHOD: 60 patients with unilateral,
      operatively treated, intra-articular calcaneal fractures were clinically and
      biomechanically evaluated >1 year postoperatively (physical examination, SF-36,
      AOFAS score, lower leg isokinetic strength, postural control and gait analysis
      including plantar pressure distribution). Results were correlated to clinical
      outcome and preoperative radiological findings (Bohler angle, Zwipp and Sanders
      Score). RESULTS: Clinical examination revealed a statistically significant
      reduction in range of motion at the tibiotalar and the subtalar joint on the
      affected side. Additionally, there was a statistically significant reduction of
      plantar flexor peak torque of the injured compared to the uninjured limb
      (p<0.001) as well as a reduction in postural control that was also more
      pronounced on the initially injured side (standing duration 4.2+/-2.9s vs. 7.6+/
      2.1s, p<0.05). Plantar pressure measurements revealed a statistically significant
      pressure reduction at the hindfoot (p=0.0007) and a pressure increase at the
      midfoot (p=0.0001) and beneath the lateral forefoot (p=0.037) of the injured
      foot. There was only a weak correlation between radiological classifications and
      clinical outcome but a moderate correlation between strength differences and the
      clinical questionnaires (CC 0.27-0.4) as well as between standing duration and
      the clinical questionnaires. Although thigh circumference was also reduced on the
      injured side, there was no important relationship between changes in lower leg
      circumference and strength suggesting that measurement of leg circumference may
      not be a valid assessment of maximum strength deficits. Self-selected walking
      speed was the parameter that showed the best correlation with clinical outcome
      (AOFAS score). CONCLUSION: Calcaneal fractures are associated with a significant
      reduction in ankle joint ROM, plantar flexion strength and postural control.
      These impairments seem to be highly relevant to the patients. Restoration of
      muscular strength and proprioception should therefore be aggressively addressed
      in the rehabilitation process after these fractures.

PMID- 21075373
TI  - Effects of fenofibrate therapy on circulating adipocytokines in patients with
      primary hypertriglyceridemia.
AB  - BACKGROUND: We investigated effects of fenofibrate therapy on endothelial
      dysfunction and adipocytokine profiles. METHODS: A randomized, single-blind,
      placebo-controlled, cross-over study was conducted in 53 patients with primary
      hypertriglyceridemia. We administered placebo or fenofibrate 160mg daily for 8
      weeks. RESULTS: When compared with placebo, fenofibrate therapy substantially
      lowered plasma levels of TNF-alpha by 6+/-3% (P=0.014) and hsCRP from 1.10 to
      0.90mg/l (P=0.004). When compared with placebo, fenofibrate therapy increased
      plasma levels of adiponectin by 17+/-4% (P=0.001), insulin sensitivity by 4+/-1%
      (as assessed by QUICKI, P=0.009), and decreased plasma levels of leptin and
      resistin by 4+/-7% (P=0.022) and 10+/-3% (P=0.001), respectively. There were
      correlations between percent changes in QUICKI and percent changes in adiponectin
      levels (r=0.279, P=0.043) or leptin (r=-0.280, P=0.042). CONCLUSIONS: Fenofibrate
      therapy significantly reduced pro-inflammatory biomarkers and improved
      adipocytokines levels and insulin sensitivity in hypertriglyceridemic patients.

PMID- 21075374
TI  - Different prognostic value of silent peripheral artery disease in type 2 diabetic
      and non-diabetic subjects with stable cardiovascular disease.
AB  - OBJECTIVE: ABI is a good predictor of morbidity and mortality in diabetic
      subjects with no known cardiovascular disease. However, its prognostic value in
      diabetic patients with prior coronary or cerebrovascular disease has not
      previously been evaluated. METHODS: Multicenter, prospective study of 1 year of
      follow-up, in 1096 patients (73.6 years, 65% males, 45.4% with diabetes) with
      cardiovascular disease and without known peripheral arterial disease. The main
      outcome measure was the first occurrence of a major cardiovascular event (non
      fatal acute coronary syndrome, non-fatal stroke, revascularization procedure, or
      cardiovascular death). Secondary endpoints included major cardiovascular events,
      cardiovascular death and death from any cause. RESULTS: Prevalence of an abnormal
      ABI (<0.9 or >1.4) was 38.2% in diabetic and 26.8% in non-diabetic subjects.
      There were 150 major cardiovascular events (38.3/1000 person-years in diabetics
      vs. 30.6/1000 person-years in non-diabetics subjects, p=0.012) and 60
      cardiovascular deaths (11.8/1000 person-years in diabetics vs. 10.7/1000 person
      years in non-diabetics subjects, p=0.156). Patients with abnormal ABI had a
      higher rate of vascular complications. There was a significant interaction
      between ABI and diabetes. In non-diabetic patients, an abnormal ABI was
      associated with an increase risk of the primary endpoint (HR 2.71; 95% CI 1.54
      4.76), cardiovascular mortality (HR 4.62; 95% CI 1.47-14.52) and total mortality
      (HR 2.80; 95% CI 1.08-7.27). These associations were not observed in patients
      with diabetes. CONCLUSION: In patients with cardiovascular disease, ABI is a good
      predictor of risk of recurrent cardiovascular events and death, only in non
      diabetic subjects.

PMID- 21075376
TI  - Altered control strategy between leading and trailing leg increases knee
      adduction moment in the elderly while descending stairs.
AB  - The aim of the study was to examine the external knee adduction moments in a
      group of older and younger adults while descending stairs and thus the
      possibility of an increased risk of knee osteoarthritis due to altered knee joint
      loading in the elderly. Twenty-seven older and 16 younger adults descended a
      purpose-built staircase. A motion capture system and a force plate were used to
      determine the subjects' 3D kinematics and ground reaction forces (GRF) during
      locomotion. Calculation of the leg kinematics and kinetics was done by means of a
      rigid, three-segment, 3D leg model. In the initial portion of the support phase,
      older adults showed a more medio-posterior GRF vector relative to the ankle
      joint, leading to lower ankle joint moments (P<0.05). At the knee, the older
      adults demonstrated a more medio-posterior directed GRF vector, increasing in
      knee flexion and adduction in the second part of the single support phase
      (P<0.05). Further, GRF magnitude was lower in the initial and higher in the mid
      portions of the support phase for the elderly (P<0.05). The results show that
      older adults descend stairs by using the trailing leg before the initiation of
      the double support phase more compared to the younger ones. The consequence of
      this altered control strategy while stepping down is a more medially directed GRF
      vector increasing the magnitude of external knee adduction moment in the elderly.
      The observed changes between leading and trailing leg in the elderly may cause a
      redistribution of the mechanical load at the tibiofemoral joint, affecting the
      initiation and progression of knee osteoarthritis in the elderly.

PMID- 21075375
TI  - Divergent roles of NF-kappaB and Egr-1 in flow-dependent restenosis after
      angioplasty and stenting.
AB  - OBJECTIVE: Restenosis after both angioplasty and stenting is flow dependent. The
      effects of flow are preventable with the antioxidant pyrrolidine dithiocarbamate
      (PDTC) after angioplasty but not after stenting. We examined to what extent these
      observations could be explained by the effect of PDTC on NF-kappaB and Egr-1, two
      transcription factors which are both flow- and redox-sensitive. METHODS: In a
      flow-modified rabbit carotid model of angioplasty and stenting, we assessed the
      effects of altered flow, injury and PDTC on expression of Egr-1 and nuclear
      binding activity of NF-kappaB. We also examined the effects of local delivery of
      decoy oligodeoxynucleotides (ODN) specific for NF-kappaB and Egr-1 on morphology
      at 28 days in normal and low flow. RESULTS: The activity of both transcription
      factors was enhanced by injury (stent>balloon alone) and was further augmented by
      low flow. PDTC markedly attenuated the activity of NF-kappaB but not Egr-1.
      Specific decoy ODN for Egr-1 attenuated intima formation in both stented and
      balloon injured vessels in both normal and low flow but had no effect on
      remodelling. In contrast while NF-kappaB decoy ODN caused a modest but
      significant reduction in intima formation, there was a striking effect on
      remodelling in low flow vessels only. CONCLUSIONS: We conclude that Egr-1 plays a
      pivotal role in intima formation under all flow conditions and that NF-kappaB
      plays a key role in flow-sensitive remodelling after angioplasty and that NF
      kappaB inhibition likely accounts for a significant part of the morphological
      effects of PDTC after vessel injury.

PMID- 21075377
TI  - The 3D trajectory of the body centre of mass during adult human walking: evidence
      for a speed-curvature power law.
AB  - During straight walking, the body centre of mass (CM) follows a 3D figure-of
      eight ("bow-tie") trajectory about 0.2 m long and with sizes around 0.05 m on
      each orthogonal axis. This was shown in 18 healthy adults walking at 0.3 to 1.4
      ms-1 on a force-treadmill (Tesio and Rota, 2008). Double integration of force
      signals can provide both the changes of mechanical energy of the CM and its 3D
      displacements (Tesio et al., 2010). In the same subjects, the relationship
      between the tangential speed of the CM, Vt, the curvature, C, and its inverse-
      the radius of curvature, r(c), were analyzed. A "power law" (PL) model was
      applied, i.e. logVt was regressed over logr(c). A PL is known to apply to the
      most various goal-directed planar movements (e.g. drawing), where the coefficient
      of logr(c), beta, usually takes values around 13. When the PL was fitted to the
      whole dataset, beta was 0.346 and variance explanation, R2, was 59.8%. However,
      when the data were split into low- and high-curvature subsets (LC, HC, arbitrary
      cut-off of C=0.05 mm-1, r(c)=20mm), beta was 0.185 in the LC (R2 0.214) and 0.486
      in the HC (R2 0.536) tracts. R2 on the whole dataset increased to 0.763 if the LC
      HC classification of the forward speed and their interaction entered the model.
      The beta coefficient, the curvature C, and the pendulum-like recovery of
      mechanical energy were lower during the double foot-ground contact phase,
      compared to the single contact. Along the CM trajectory, curvature and muscle
      power output peaked together around the inversions of lateral direction. Non-zero
      torsion values were randomly distributed along 60% of the trajectory, suggesting
      that this is not segmented into piecewise planar tracts. It is proposed that the
      trajectory can be segmented into one tract that is more actively controlled (tie)
      where a PL fits poorly and another tract which is more ballistic (bow) where a PL
      fits well. Results need confirmation through more appropriate 3D PL modelling.

PMID- 21075378
TI  - Time course and extent of functional recovery during the first postoperative year
      after minimally invasive total hip arthroplasty with two different surgical
      approaches--a randomized controlled trial.
AB  - While others have reported short-term comparisons between various minimally
      invasive surgical (MIS) approaches to total hip arthroplasty (THA) and their
      conventional analogues, longer-term data is lacking, as is information indicating
      whether MIS approaches to THA provide a biomechanically complete recovery.
      Furthermore, different MIS approaches have not been compared. Our approaches of
      interest were a one-incision modified Watson-Jones, and a two-incision approach.
      HYPOTHESES: (1) There are significant differences in gait recovery patterns
      between the two surgical groups and (2) THA subjects have significant differences
      in function one year after surgery compared to control subjects. To test these
      hypotheses, THA candidates (n=26) were randomized to receive one of these MIS
      approaches and evaluated preoperatively, and postoperatively at 3 weeks, and at
      3, 6 and 12 months. Evaluations included three-dimensional gait analysis and 24
      hour step-counts. The same data were obtained from 25 control subjects. Recovery
      time-course was assessed using repeated measures ANOVA. T-tests were used to
      compare controls with the pooled group of THA subjects. We found no differences
      between the two THA surgical groups regarding the time-course of recovery
      (p>=0.591). Although recovery was statistically complete by 3 months
      postoperatively for all variables, there were significant differences from
      controls at 12 months. Most notably, the external hip adduction moment, which
      reflects hip abductor function, was more than one standard deviation below normal
      (p<0.001). THA subject inactivity could not explain the gait differences, since
      one year after surgery daily step counts were not significantly different from
      controls (p=0.346). More work is necessary to determine ways to improve
      biomechanical outcomes for today's patients with high expectations for function
      and implant longevity.

PMID- 21075379
TI  - Role of the shape of various bacteria in their separation by Microthermal Field
      Flow Fractionation.
AB  - The steady-state movement of the spherical and non-spherical particles, such as
      prolate or oblate rotational ellipsoids, cylinders, or parallelepipeds, suspended
      in a liquid and exposed to a unidirectional temperature gradient, is analyzed
      theoretically. The differences in the ratios of the rotational to translational
      diffusion coefficients of the non-spherical to spherical particles, the
      heterogeneity of thermal conductivity of the particle body, and the heterogeneity
      in surface chemical nature make possible to separate the particles according to
      differences in shape. Preliminary experimental separations of Gram-positive and
      Gram-negative, nearly spherical and rod-shaped bacteria performed by Microthermal
      Field-Flow Fractionation confirmed that the fractionation of the cells according
      to differences in shape is possible.

PMID- 21075380
TI  - Regioisomeric analysis of triacylglycerols using silver-ion liquid chromatography
      atmospheric pressure chemical ionization mass spectrometry: comparison of five
      different mass analyzers.
AB  - Silver-ion high-performance liquid chromatography (HPLC) coupled to atmospheric
      pressure chemical ionization mass spectrometry (APCI-MS) is used for the
      regioisomeric analysis of triacylglycerols (TGs). Standard mixtures of TG
      regioisomers are prepared by the randomization reaction from 8 mono-acid TG
      standards (tripalmitin, tristearin, triarachidin, triolein, trielaidin,
      trilinolein, trilinolenin and tri-gamma-linolenin). In total, 32 different
      regioisomeric doublets and 11 triplets are synthesized, separated by silver-ion
      HPLC using three serial coupled chromatographic columns giving a total length of
      75cm. The retention of TGs increases strongly with the double bond (DB) number
      and slightly for regioisomers having more DBs in sn-1/3 positions. DB positional
      isomers (linolenic vs. gamma-linolenic acids) are also separated and their
      reverse retention order in two different mobile phases is demonstrated. APCI mass
      spectra of all separated regioisomers are measured on five different mass
      spectrometers: single quadrupole LC/MSD (Agilent Technologies), triple quadrupole
      API 3000 (AB SCIEX), ion trap Esquire 3000 (Bruker Daltonics), quadrupole time-of
      flight micrOTOF-Q (Bruker Daltonics) and LTQ Orbitrap XL (Thermo Fisher
      Scientific). The effect of different types of mass analyzer on the ratio of [M+H
      R(i)COOH](+) fragment ions in APCI mass spectra is lower compared to the effect
      of the number of DBs, their position on the acyl chain and the regiospecific
      distribution of acyl chains on the glycerol skeleton. Presented data on [M+H
      R(i)COOH](+) ratios measured on five different mass analyzers can be used for the
      direct regioisomeric determination in natural and biological samples.

PMID- 21075381
TI  - Association between oxidative stress and masked hypertension in a multi-ethnic
      population of obese children and adolescents.
AB  - OBJECTIVE: To evaluate whether oxidative stress is correlated with adiposity,
      obesity-related metabolic abnormalities, and ambulatory blood pressure (ABP) in a
      multi-ethnic pediatric population. STUDY DESIGN: We conducted a prospective study
      enrolling 42 obese children (age, 12.8 +/- 2.4 years) and 34 non-obese children
      (age, 11.8 +/- 3.4 years). We measured urine 8-isoprostane and hydrogen peroxide
      (markers of oxidative stress) in both obese and non-obese groups. In the obese
      group, we measured the 24-hour ABP and obtained an oral glucose tolerance test,
      lipid panel, interleukin-6, and tumor necrosis factor-alpha. RESULTS: 8
      isoprostane and hydrogen peroxide were correlated with body mass index standard
      deviation score and waist circumference. The mean 8-isoprostane and hydrogen
      peroxide levels of the obese group were higher than those of the non-obese group.
      In the subset of obese subjects who underwent ABP monitoring, 8-isoprostane was
      correlated with mean 24-hour systolic blood pressure: within the obese group, 8
      isoprostane was higher in obese children with elevated mean 24-hour systolic
      blood pressure. CONCLUSIONS: Our findings provide evidence of a significant
      correlation between oxidative stress, adiposity, and blood pressure in children.
      Longitudinal studies in a larger population sample are needed to validate the
      association between elevated urine 8-isoprostane level and cardiovascular risk
      factors in an obese pediatric population.

PMID- 21075382
TI  - Novel mechanism of mitral regurgitation after lung transplantation in a patient
      with scleroderma and pulmonary hypertension.

PMID- 21075383
TI  - Mechanisms underlying increased reactivity of pulmonary arteries contralateral to
      a localized high-flow anastomosis.
AB  - OBJECTIVES: Our model of a systemic-pulmonary shunt exhibits enhanced reactivity
      of pulmonary arteries contralateral to a localized shunt between the left lower
      lobe pulmonary artery and aorta relative to those of ipsilateral or control
      pulmonary arteries 48 hours after anastomosis. We examined the contribution of
      nitric oxide, cyclooxygenase, lipoxygenase, or cytochrome P450 production to
      mediating this enhanced reactivity. METHODS: We created a surgical end-to-side
      anastomosis of the left lower lobe pulmonary artery to the aorta. Forty-eight
      hours later, we tested tension of pulmonary artery rings from the right and left
      lower lobes for contraction to the thromboxane mimetic U46619 in the presence of
      vehicle or inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450,
      or lipoxygenase. Western blots of pulmonary artery homogenates were probed for
      endothelial nitric oxide synthase or isoforms metabolizing arachidonic acid.
      Eicosanoid products from intact pulmonary artery rings were detected using
      labeled arachidonic acid and high-performance liquid chromatography separation.
      RESULTS: Enhanced reactivity of unshunted right pulmonary arteries over that of
      left pulmonary arteries from high-flow hosts was not eliminated by inhibitors of
      nitric oxide synthase, cyclooxygenase, cytochrome P450. Treatment with 2
      different lipoxygenase inhibitors, nordihydroguaiaretic acid and cinnamyl-3,4
      dihydroxy-alpha-cyanocinnamate, closed the difference in contractility of shunted
      and unshunted pulmonary arteries. Pulmonary arteries contralateral to shunts
      metabolized arachidonic acid to 12-hydroxyeicosatetraenoic acid in greater
      quantities than analogous pulmonary arteries from the experimental left or
      control pulmonary arteries. CONCLUSIONS: Forty-eight hours after anastomosis,
      enhanced reactivity of contralateral pulmonary arteries is attributable in part
      to increased lipoxygenase products as opposed to nitric oxide or other eicosanoid
      products.

PMID- 21075384
TI  - Effects of a localized high-flow anastomosis between the aorta and left lower
      lobe pulmonary artery on great vessel flow and pulmonary arterial reactivity in
      the contralateral lung.
AB  - OBJECTIVES: We sought to assess the effects of a localized anastomosis between
      the aorta and left lower lobe pulmonary artery on flows through central vessels
      and on the vascular reactivity of small pulmonary arteries distal or
      contralateral to the shunt. METHODS: Flow rates in major vessels and tensions
      from small pulmonary arteries from the left and right lower lobes were determined
      48 hours after creation of an end-to-side anastomosis of the left lower lobe
      pulmonary artery to the aorta. RESULTS: Anastomoses increased flow through the
      left lower lobe pulmonary artery from 194+/-6 to 452+/-18 mL/min immediately
      after anastomosis to 756+/-19 mL/min by the time of harvest (n=88, P<.05). Flow
      rates in main pulmonary arteries from hosts with anastomoses were lower (557+/-26
      vs 1033+/-244 mL/min), whereas aortic root flows were not different from control
      values (1370+/-53 vs 1120+/-111 mL/min; P=.07). Wet/dry weights of both lungs and
      aortic flow rates were proportional to shunt flow rates. Pulmonary artery rings
      harvested from the right (unshunted) lobes of high-flow hosts exhibited increased
      reactivity to the thromboxane agonist U46619 and phenylephrine relative to those
      of left pulmonary arteries from the same animal or those of control hosts.
      CONCLUSIONS: Our studies are the first to identify enhanced reactivity of
      pulmonary arteries in a lung contralateral to a localized high-output shunt
      between an aorta and pulmonary artery. These observations suggest that patients
      with localized systemic-to-pulmonary shunt could exhibit modified vascular tone
      in remote pulmonary arteries.

PMID- 21075385
TI  - Inhibition of aberrant androgen receptor induction of prostate specific antigen
      gene expression, cell proliferation and tumor growth by 17alpha-estradiol in
      prostate cancer.
AB  - PURPOSE: Androgen independent prostate cancer growth and metastasis are a major
      cause of prostate cancer death. Aberrant androgen receptor activation due to
      androgen receptor mutation is an important mechanism of androgen independence. We
      determined the effectiveness and mechanism of 17alpha-estradiol (Sigma(r)) in
      blocking aberrant androgen receptor activation due to androgen receptor mutation.
      MATERIALS AND METHODS: We used LNCaP and MDA Pca-2b prostatic tumor cells
      (ATCC(r)) containing a mutated androgen receptor and WT estrogen receptor beta to
      test 17alpha-estradiol inhibition of aberrant androgen receptor activation of
      prostate specific antigen gene expression and cell growth. Cotransfection
      analysis was used to further elucidate the mechanism of 17alpha-estradiol action.
      Xenograft animals with an LNCaP prostate tumor were prepared to study the in vivo
      effect of 17alpha-estradiol on tumor growth inhibition. RESULTS: In LNCaP cells
      17alpha-estradiol produced a dose dependent inhibition of cyproterone acetate
      (Sigma) or dihydrotestosterone induced prostate specific antigen gene expression.
      In MDA Pca-2b cells 17alpha-estradiol inhibited cortisol (Sigma) induced prostate
      specific antigen expression and blocked dihydrotestosterone and cortisol induced
      cell proliferation in LNCaP and MDA Pca-2b cells, respectively. Cotransfection
      analysis showed that 17alpha-estradiol inhibition of aberrant androgen receptor
      activation of prostate specific antigen gene expression was medicated via
      estrogen receptors. In xenograft mice with LNCaP prostate cancer 17alpha
      estradiol but not 17beta-estradiol (Sigma) significantly inhibited tumor growth,
      although each estrogen tended to decrease tumor growth. CONCLUSIONS: Results
      suggest that 17alpha-estradiol with less classic estrogenic activity is a
      potential therapeutic agent for androgen independent prostate cancer due to
      androgen receptor mutation.

PMID- 21075386
TI  - Intercostal vessels and nerves are at risk for injury during supracostal
      percutaneous nephrostolithotomy.
AB  - PURPOSE: We characterized key intercostal anatomical relationships relevant to
      supracostal percutaneous nephrostolithotomy using anatomical dissection.
      MATERIALS AND METHODS: We performed 20 cadaveric dissections of the 11th
      intercostal space to characterize key anatomical relationships relevant to
      percutaneous upper pole renal access. Specific data recorded included intercostal
      rib distance at the lateral border of the paraspinous muscles, and the mid
      scapular and posterior axillary lines. We also recorded the distance between the
      12th and 11th ribs to the intercostal nerve, artery and vein at the same 3 sites.
      RESULTS: The average intercostal distance was 21, 23 and 26 mm at the lateral
      border of the paraspinous muscles, and the mid scapular and posterior axillary
      lines, respectively. The intercostal nerve was exposed to injury in 85%, 100% and
      100% of patients at the 3 sites, respectively. The intercostal artery was exposed
      below the 11th rib in 30%, 60% and 70% of cadavers, respectively, and it was 6 mm
      from the rib in 25% of interspaces. The intercostal vein, which was exposed below
      the 11th rib in 0%, 5% and 10% of cadavers, respectively, was least likely to be
      injured. CONCLUSIONS: Intercostal vessels are at risk for damage during
      percutaneous nephrostolithotomy in a significant number of patients. Access
      placement lateral to the paraspinous muscles and in the lower half of the 11th
      intercostal space may decrease damage to the intercostal artery and nerve. Injury
      to the intercostal vessels and nerve may explain the increased risk of bleeding
      and pain during supracostal percutaneous nephrostolithotomy. Minimizing injury
      may decrease blood loss and pain.

PMID- 21075387
TI  - Modulation of stretch evoked adenosine triphosphate release from bladder
      epithelium by prostaglandin E2.
AB  - PURPOSE: We previously reported that cyclooxygenase inhibitors improved storage
      function in rats with detrusor overactivity caused by cerebral infarction via C
      fiber suppression but the precise mechanism underlying this effect remained
      unclear. In this study we investigated the effects of cyclooxygenase inhibitors
      on stretch evoked adenosine triphosphate and prostaglandin E(2) release from
      bladder epithelium. MATERIALS AND METHODS: Whole bladders excised from normal
      rats were fixed vertically in an organ bath filled with Krebs solution. Bladders
      were infused with 0.3 ml Krebs solution (baseline), followed by 0.9 ml vehicle or
      1.5 ml vehicle/drug solution, or 0.3 ml protamine sulfate (Wako Pure Chemical
      Industries, Osaka, Japan), followed by 0.3 ml prostaglandin E(2) (Nacalai Tesque,
      Kyoto, Japan). Solutions were allowed to stand for 10 minutes and collected.
      Adenosine triphosphate and prostaglandin E(2) concentrations were measured by
      luciferin-luciferase assay and enzyme-linked immunoassay, respectively. RESULTS:
      Adenosine triphosphate and prostaglandin E(2) release from bladder epithelium was
      increased by distention in volume dependent fashion. A 100 MUM dose of the
      nonselective cyclooxygenase inhibitors FYO-750, ketoprofen and indomethacin
      significantly suppressed the increased adenosine triphosphate and prostaglandin
      E(2) release. Inhibition of adenosine triphosphate release by 100 MUM FYO-750 and
      indomethacin was antagonized by prostaglandin E(2) co-injection. Prostaglandin
      E(2) increased adenosine triphosphate release in a nondistending condition, and
      the 1 MUM of the selective EP1 and EP3 receptor antagonists ONO-8711 and ONO-AE5
      599, respectively, significantly suppressed the increased adenosine triphosphate
      release. CONCLUSIONS: Results indicate that cyclooxygenase inhibitors suppress
      adenosine triphosphate release from bladder epithelium via decreasing
      prostaglandin E(2). EP1 and/or EP3 receptors appear to participate in this
      effect.

PMID- 21075388
TI  - The relationship between prostaglandin E receptor 1 and cyclooxygenase I
      expression in guinea pig bladder interstitial cells: proposition of a signal
      propagation system.
AB  - PURPOSE: We explored the structural relationship between enzymes producing
      prostaglandin (cyclooxygenase I) and 1 of the receptor families that respond to
      prostaglandin (prostaglandin E receptor 1) in the bladder muscle. MATERIALS AND
      METHODS: Nine male guinea pigs were sacrificed by cervical dislocation. Bladders
      were removed and fixed in 4% paraformaldehyde in phosphate buffered saline.
      Frozen sections (10 MUm) were cut and stained with antibodies to prostaglandin E
      receptor type 1, cyclooxygenase I and vimentin. RESULTS: Prostaglandin E
      receptors 1 was identified on smooth muscle cells, and vimentin positive surface
      muscle and intramuscular interstitial cells. Muscle staining was less intense
      than on interstitial cells and had a punctuate appearance. Prostaglandin E
      receptor 1 expression on interstitial cells was highly localized. Discrete
      regions of intense staining were noted on interstitial cell processes.
      Cyclooxygenase I was also expressed in muscle interstitial cells. Cyclooxygenase
      I positive interstitial cells were more prevalent in the muscle bundles of the
      inner muscle than in the outer muscle layers. Cyclooxygenase I staining was noted
      on discrete regions of the cell or cell processes. Double staining with
      prostaglandin E receptor 1 and cyclooxygenase I suggested that cell regions
      expressing the former are different from those expressing the latter.
      CONCLUSIONS: The discovered arrangement of prostaglandin E receptor 1 and
      cyclooxygenase I may have the potential to facilitate the propagation of signals
      in the interstitial cell network. Such a signaling system may have a role in
      coordinating events, as in bladder pathology, facilitating the global coordinated
      changes associated with bladder wall remodeling.

PMID- 21075389
TI  - Sprayed fibrin sealant as the sole hemostatic agent for porcine laparoscopic
      partial nephrectomy.
AB  - PURPOSE: Tisseel(r) is used to control minor bleeding during laparoscopic
      procedures. The DuploSpray MISTM spray system allows thin, even application over
      a larger surface area. We use sprayed Tisseel as the sole agent to control
      hemorrhage and seal the renal collecting system after severe porcine laparoscopic
      partial nephrectomy. METHODS AND MATERIALS: We performed staged bilateral severe
      laparoscopic partial nephrectomy in 12 Yucatan pigs using a longitudinal cut from
      upper to lower pole through the entire collecting system. In each pig 1 kidney
      was harvested immediately while the other was harvested after 4 weeks. After
      hilar clamping laparoscopic partial nephrectomy was done with cold scissors in 6
      pigs while LigaSureTM was used in the other 6. Sprayed Tisseel was applied, and
      bleeding and urinary leakage were evaluated. Additional Tisseel was applied for
      repeat bleeding. We performed retrograde pyelogram (chronic) and burst pressure
      testing of the arterial and collecting systems. RESULTS: All animals survived 4
      weeks. One urinoma was seen on retrograde pyelogram in the cold cut group.
      Average hilar clamp time was similar in the acute and chronic study arms. Average
      estimated blood loss was significantly less in the LigaSure group (p = 0.0045).
      Average arterial burst pressure was significantly different in the chronic and
      acute groups (605.8 vs 350.4 mm Hg, p = 0.008) but average collecting system
      burst pressure was similar (186.3 and 149.5 mm Hg, respectively). CONCLUSIONS:
      Sprayed Tisseel without suturing effectively sealed the arterial and collecting
      system after severe laparoscopic partial nephrectomy in the porcine model.

PMID- 21075390
TI  - Effects of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus
      extracts on risk factors for urinary calcium oxalate stones in rats.
AB  - PURPOSE: We evaluated the antilithic effect of Orthosiphon grandiflorus, Hibiscus
      sabdariffa and Phyllanthus amarus extracts on known risk factors for calcium
      oxalate stones in rats. MATERIALS AND METHODS: We divided 30 male Wistar rats
      into 5 equal groups. Controls were fed a standard diet and the remaining groups
      received a 3% glycolate diet for 4 weeks to induce hyperoxaluria. One glycolate
      fed group served as the untreated group and the others were given oral extracts
      of Orthosiphon grandiflorus, Hibiscus sabdariffa or Phyllanthus amarus at a dose
      of 3.5 mg daily. We collected 24-hour urine and blood samples. Kidneys were
      harvested for histological examination. We measured the renal tissue content of
      calcium and oxalate. RESULTS: The Hibiscus sabdariffa group showed significantly
      decreased serum oxalate and glycolate, and higher oxalate urinary excretion. The
      Phyllanthus amarus group showed significantly increased urinary citrate vs the
      untreated group. Histological examination revealed less CaOx crystal deposition
      in the kidneys of Hibiscus sabdariffa and Phyllanthus amarus treated rats than in
      untreated rats. Those rats also had significantly lower renal tissue calcium
      content than untreated rats. All parameters in the Orthosiphon grandiflorus
      treated group were comparable to those in the untreated group. CONCLUSIONS:
      Hibiscus sabdariffa and Phyllanthus amarus decreased calcium crystal deposition
      in the kidneys. The antilithic effect of Hibiscus sabdariffa may be related to
      decreased oxalate retention in the kidney and more excretion into urine while
      that of Phyllanthus amarus may depend on increased urinary citrate. In contrast,
      administering Orthosiphon grandiflorus had no antilithic effect.

PMID- 21075391
TI  - Segmental renal artery pseudoaneurysm after partial nephrectomy.

PMID- 21075393
TI  - Contractility and pacemaker cells in the prostate gland.
AB  - PURPOSE: We focused on the current opinion on mechanisms generating stromal tone
      in the prostate gland. MATERIALS AND METHODS: We selected the guinea pig as the
      main species for investigation since its prostate has a high proportion of smooth
      muscle that undergoes age related changes similar in many respects to that in
      humans. The main techniques that we used were tension recording and
      electrophysiology. RESULTS: We previously reported distinct electrical activity
      and cell types in the prostate, and speculated on their functional roles. We
      believe that a specialized group of c-kit immunoreactive prostatic interstitial
      cells that lie between glandular epithelium and smooth muscle stroma have a role
      similar to that of gastrointestinal interstitial cells of Cajal, generating the
      pacemaker signal that manifests as slow wave activity and triggers contraction in
      smooth muscle cells in guinea pig prostates. CONCLUSIONS: Since changes in muscle
      tone are involved in the etiology of age dependent prostate specific conditions
      such as benign prostatic hyperplasia, knowledge of the electrical properties of
      the various prostatic cell types and their interactions with each other, with
      nerves and with the hormonal environment, and how these factors change with age
      is of considerable medical importance.

PMID- 21075394
TI  - Intra-abdominal testis: histological alterations and significance of biopsy.
AB  - PURPOSE: Intra-abdominal testes represent only 5% of undescended testes. Review
      of the literature reveals that few data exist on the histological analysis of
      intra-abdominal testes. We studied histological alterations in intra-abdominal
      testes in relation to patient age at orchiopexy. MATERIALS AND METHODS: A total
      of 57 boys underwent laparoscopy for impalpable undescended testes between
      October 2002 and June 2005. Testicular biopsies were taken from intra-abdominal
      testes, fixed in 3% glutaraldehyde, embedded in Epon, sectioned at 1 micron
      thickness and stained with toluidine blue. Histomorphometric analysis was
      performed by light microscopy. Effect of age at operation on histological
      evaluation of abdominal testes was also studied. RESULTS: Testicular biopsies
      from 29 patients with intra-abdominal testes showed the histological alterations
      of decreased mean diameter of seminiferous tubules, germinal cell depletion (55%)
      and presence of microliths (6.9%). CONCLUSIONS: As age at orchiopexy increases,
      deviation from the norm is more evident and absence of germ cells on biopsy
      becomes more pronounced, reaching a rate of 93% after age 3 years. Further
      studies on orchiopexy with or without biopsy in the first few months of life
      would likely improve our understanding and treatment of cryptorchidism.

PMID- 21075396
TI  - Paclitaxel inhibits ureteral smooth muscle cell proliferation and collagen
      production in the absence of cell toxicity.
AB  - PURPOSE: Urinary tract stricture results from excess collagen deposition at an
      injured area. Paclitaxel (Sigma-Aldrich(r)) prevents coronary artery restenosis
      by inhibiting vascular smooth muscle cell proliferation and collagen production.
      We evaluated the effects of paclitaxel on ureteral smooth muscle cell
      proliferation and collagen production. MATERIALS AND METHODS: Three phases of
      experiments were done in canine smooth muscle cells. In phase 1 we used
      proliferation assay to study smooth muscle cells exposed to various
      concentrations of paclitaxel during 7 days. Phase 2 consisted of 6-day enzyme
      linked immunosorbent assay to detect the total amount of type III collagen
      produced by smooth muscle cells exposed to paclitaxel. In phase 3 we assessed
      smooth muscle cell membrane damage using a lactate dehydrogenase cytotoxicity
      assay in which cells were exposed to escalating paclitaxel concentrations for 14
      days. RESULTS: Proliferation studies showed that 10 and 100 nM paclitaxel
      significantly inhibited ureteral smooth muscle cell proliferation. Enzyme-linked
      immunosorbent assay revealed significantly decreased type III collagen production
      at 100 nM. Cytotoxicity testing showed that 1 to 100 nM paclitaxel did not harm
      smooth muscle cells. CONCLUSIONS: Paclitaxel effectively inhibits canine ureteral
      smooth muscle cell proliferation and collagen production without toxicity to
      smooth muscle cells at concentrations up to 100 nM. These results may ultimately
      translate into new methods of preventing and treating urinary stricture disease.

PMID- 21075397
TI  - Editorial comment.

PMID- 21075398
TI  - Clear cell sarcoma of the kidney.

PMID- 21075399
TI  - Super selective radio embolization of the porcine kidney with 90yttrium resin
      microspheres: a feasibility, safety and dose ranging study.
AB  - PURPOSE: We determined whether super selective radio embolization of the porcine
      kidney was technically feasible and evaluated histopathological changes in the
      treatment target zone (upper or lower renal pole), adjacent nontargeted kidney,
      and adjacent and distant organs after administering (90)Y labeled vs bland resin
      microspheres. MATERIALS AND METHODS: We performed super selective radio
      embolization with (90)Y resin microspheres in 1 kidney and with an equivalent
      number of bland microspheres in the corresponding pole of the contralateral
      kidney as a control. The aim was to achieve radio embolization of a target zone
      equivalent to approximately a third of the kidney volume. A pathologist
      independently graded macroscopic and microscopic changes in the kidney, and
      adjacent and distant tissue resulting from incremental increases (0.15 to 0.35
      GBq) in implanted activity in 6 pigs. RESULTS: We recorded grade 4 histological
      changes in the treatment target zone (upper or lower renal pole) in 5 of 6 pigs
      after injecting (90)Y resin microspheres with evidence of nephron sparing effects
      in the adjacent renal tissue at the lowest activity. At activity greater than 0.3
      GBq increasing damage was noted to adjacent renal tissue beyond the treatment
      target zone. No toxicity was evident in adjacent or distant organs. CONCLUSIONS:
      Delivery of highly targeted intra-arterial radiotherapy to the kidney is feasible
      and safe in the pig model. Further evaluation is warranted as a potential
      treatment for advanced renal cell carcinoma or for localized disease in patients
      who are not candidates for surgery.

PMID- 21075400
TI  - The effects of physiological estrogen concentration on the immune response of
      urothelial carcinoma cells to bacillus Calmette-Guerin.
AB  - PURPOSE: Meta-analysis has shown that bacillus Calmette-Guerin is less effective
      in females undergoing treatment for urothelial carcinoma. Urothelial carcinoma
      cells express immune regulatory proteins as a consequence of bacillus Calmette
      Guerin induced, nuclear factor kappaB signaling. Nuclear factor kappaB is
      influenced by estrogen receptor binding. We evaluated the effect of the
      physiological estradiol concentration on the expression of bacillus Calmette
      Guerin induced, nuclear factor kappaB regulated immune proteins. MATERIALS AND
      METHODS: We determined the estrogen receptor expression status of human
      urothelial carcinoma cell lines by reverse transcriptase-polymerase chain
      reaction. The functional status of estrogen receptor signaling was established
      using estrogen receptor reporter constructs. We used gene expression profiling of
      urothelial carcinoma cells combined with reverse transcriptase-polymerase chain
      reaction to identify the nuclear factor kappaB dependent immune regulatory
      proteins expressed in response to bacillus Calmette-Guerin. We determined the
      influence of the estradiol concentration on bacillus Calmette-Guerin dependent
      interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c
      motif) ligand 20 gene expression by quantitative reverse transcriptase-polymerase
      chain reaction. RESULTS: Urothelial carcinoma cell lines expressed functional
      estrogen receptor. Nuclear factor kappaB signaling was inhibited by estradiol in
      a dose and estrogen receptor dependent manner. Urothelial carcinoma cell
      expression of interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and
      chemokine (c-c motif) ligand 20 was up-regulated in response to bacillus Calmette
      Guerin in a nuclear factor kappaB dependent manner. There was a significant dose
      dependent effect of estradiol on the expression of these genes in bacillus
      Calmette-Guerin treated urothelial carcinoma cells. CONCLUSIONS: The
      physiological concentration of estrogen influences nuclear factor kappaB
      signaling and bacillus Calmette-Guerin dependent gene expression. Serum estradiol
      fluctuations in women may influence the response of urothelial carcinoma to
      intravesical bacillus Calmette-Guerin treatment.

PMID- 21075401
TI  - [Life styles and risk factors for osteoporosis].

PMID- 21075402
TI  - [New era in antiplatelet therapy based on results from recent clinical trials].
AB  - Antiplatelet therapy has been successful in reducing mortality and morbidity in
      cardiovascular diseases (e.g. acute coronary syndromes). Recent advances in
      understanding the molecular basis of the role of platelets in atherothrombosis
      have enabled the development of new agents with the potential to further reduce
      mortality and morbidity. Some limitations associated with the use of aspirin and
      clopidogrel have led to potential alternatives, including more potent ADP
      antagonists such as prasugrel, ticagrelor, cangrelor, and thrombin receptor
      antagonists, which have shown additional benefit in large randomized controlled
      trials. These new agents open a realistic prospect of a personalized choice of
      the most appropriate antiplatelet therapy tailored for an individual patient and
      a clinical condition.

PMID- 21075403
TI  - [Diagnosis and treatment of nocturnal paroxysmal hemoglobinuria].

PMID- 21075404
TI  - Lipid in the livers of adolescents with nonalcoholic steatohepatitis: combined
      effects of pathways on steatosis.
AB  - Fatty liver is a prerequisite for the development of nonalcoholic steatohepatitis
      (NASH). The homeostasis of hepatic lipid is determined by the dynamic balance of
      multiple pathways introducing lipids into or removing lipids from hepatocytes. We
      aim to study the different contributions of major lipid pathways to fat
      deposition in NASH livers. Expression of the lipid metabolism-related genes was
      analyzed by microarray and quantitative real-time polymerase chain reaction
      analysis. The expression levels of genes responsible for the rate-limiting steps
      of fatty acid uptake (CD36, FABPpm, SLC27A2, and SLC27A5), de novo synthesis
      (ACACB), oxidation (CPT-1), and very low-density lipoprotein (VLDL) secretion
      (ApoB) were used to evaluate the relative activity of each pathway. The
      expression levels for CD36 and CPT-1 were confirmed by Western blot analysis.
      Fatty acid uptake pathways were up-regulated to a higher degree than other
      pathways. The de novo synthesis pathway was also up-regulated more than both VLDL
      secretion and fatty acid oxidation pathways. In contrast to other NASH livers,
      one NASH liver exhibited lower ApoB and CPT-1 expression levels than normal
      controls. The increased fatty acid uptake and de novo synthesis were the most
      common causes for steatosis in NASH patients. In a rare case, impaired VLDL
      secretion and fatty acid oxidation contributed to the development of steatosis.
      Our study promises a simple method for the determination of why hepatic steatosis
      occurs in individual patients. This method may allow specific targeting of
      therapeutic treatments in individual patients.

PMID- 21075405
TI  - Molecular identification and characterization of the intervening sequences (IVSs)
      within 23S ribosomal RNA (rRNA) genes of Taylorella asinigenitalis isolated in
      France.
AB  - In the helix 25 region, 32 French Taylorella asinigenitalis isolates carried at
      least one 23S rRNA gene not containing intervening sequences (IVSs). No IVSs in
      the region were identified in three isolates and the other remaining 29 isolates
      carried one or more IVSs (UCD-1(T)IVS1A, UCD-1(T)IVS1B and UK-1IVS1B) described
      already and two new kinds of IVS (TaIVS1C and TaIVS1D). In the helix 45 region,
      no T. asinigenitalis isolates not carrying any IVSs were identified. UK-1IVS2B
      was identified in the region from 26 isolates. Five new kinds of IVSs (TaIVS2D,
      E, F, G and H) occurred in the region in the 13 isolates. Distinctly different
      tandem repeat units (RS48 and RS32 and RS-A, -B and -C) were evident in both
      regions, respectively, from the French (n=32) and American (n=3) T.
      asinigenitalis isolates. Thus, several different kinds of tandem repeat units and
      their combinations in IVSs in both regions within the gene were shown in 32
      French isolates.

PMID- 21075406
TI  - Seroprevalence of canine herpesvirus-1 in Turkish dog population.
AB  - Canine herpesvirus-1 (CHV-1) is the agent of reproductive and respiratory
      disorders in adult dogs, and the infection generally results in haemorrhagic
      disease conditions and neonatal death. In this study, virus neutralisation test
      that used complement (VNT) as well as in-house ELISA were utilised to investigate
      the CHV-1 seroprevalence in the Turkish dog population. Among the 560 serum
      samples, 39.3% of the samples tested by ELISA were CHV-1 positive while 29.4% of
      the samples tested by VNT were CHV-1 positive. Compared to the individual dogs
      (39.0%), there was a higher CHV-1 seroprevalence (62.1%) found in the colony dogs
      (62.1%) (p=0.0002). However, there was an insignificant difference between male
      and female dogs. Although the highest antibody prevalence (56.7%) was found in
      Golden Retrievers, there were no significant variations detected among the dog
      breeds used in this study. Neutralizing antibody titres were very low (?1:16) in
      a high portion of the tested animals, confirming the rapid decrease of CHV-1
      antibodies after the course of infection. The results of this study show that CHV
      1 seroprevalence is moderately high in the Turkish dog population.

PMID- 21075407
TI  - Osteogenic proliferation and differentiation of canine bone marrow and adipose
      tissue derived mesenchymal stromal cells and the influence of hypoxia.
AB  - The aim of this study was to compare the osteogenic and proliferative potential
      of canine mesenchymal stromal cells (cMSCs) derived from bone marrow (BM-cMSCs)
      and adipose tissue (AT-cMSCs). Proliferation potential was determined under
      varying oxygen tensions (1%, 5%, and 21% O(2)). Effects of reduced oxygen levels
      on the osteogenic differentiation of AT-cMSCs were also investigated. AT-cMSCs
      proliferated at a significantly faster rate than BM-cMSCs, although both cell
      types showed robust osteogenic differentiation. Culture in 5% and 1% O(2)
      impaired proliferation in cMSC from both sources and osteogenic differentiation
      in AT-cMSCs. Our data suggests that AT-cMSCs might be more suitable for use in a
      clinical situation, where large cell numbers are required for bone repair, due to
      their rapid proliferation combined with robust osteogenic potential. Our data
      also suggests that the inhibitory effects of hypoxia on both cell proliferation
      and differentiation should be considered when using MSCs in a potentially hypoxic
      environment such as a fracture site.

PMID- 21075408
TI  - Term placenta shows methylation independent down regulation of Cyp19 gene in
      animals with retained fetal membranes.
AB  - Retention of fetal membranes (RFM) is the major post-partum disorder in dairy
      cattle. Cyp19 gene encodes the aromatase enzyme responsible for catalyzing the
      rate limiting step in estrogen biosynthesis, an important hormone for placental
      maturation and expulsion. The present study was aimed for comparative analysis of
      Cyp19 gene expression and its epigenetic regulation in placental cotyledons of
      animals with and without RFM. Significantly lower expression of Cyp19 gene was
      found in placental samples of RFM affected animals in comparison to normal
      animals. Methylation analysis of 5 CpG dinucleotides of placenta specific Cyp19
      gene promoter I.1 and proximal promoter, PII showed hypo-methylation of both PI.1
      and PII in term placenta of normal and diseased animals. In conclusion, a
      mechanism other than promoter methylation is responsible for decreased aromatase
      expression in placental cotyledons of animals suffering from RFM.

PMID- 21075409
TI  - Genetic variation of major histocompatibility complex BLB2 gene exon 2 in Hebei
      domestic chicken.
AB  - Genetic variation of MHC BLB2 gene exon 2 in Hebei domestic chicken was
      investigated, after PCR and sequencing of a 374bp fragment (containing entire
      exon 2 (270bp) of BLB2 gene) in 76 individuals. The results showed that along
      this fragment, there were 69 variable sites, of which 18 were novel variations,
      and 82 estimated haplotypes with the diversity of 0.960. In Hebei domestic
      chicken, the nucleotide diversity (pi), the average number of nucleotide
      differences (k), the average number of nucleotide diversity of synonymous
      substitution (pi(s)) and non-synonymous substitution (pi(a)) in BLB2 gene exon 2
      were 0.098, 24.688, 0.075, and 0.106, respectively; nine non-synonymous
      substitutions was exclusively found in the peptide-binding sites (PBS) region of
      BLB2 gene exon 2, inferring that these unique substitutions might be helpful to
      resist some special bacteria and pathogens. The higher genetic diversity of MHC
      BLB2 gene exon 2 in Hebei domestic chicken might be consistent with its more
      robust disease resistance.

PMID- 21075410
TI  - [Ocular myasthenia: diagnosis and treatment].
AB  - Myasthenia gravis is a rare, auto-immune disorder of the neuromuscular junction.
      Onset signs frequently involve ocular muscles, accounting for ptosis and/or
      diplopia in more than 75% of cases. Among the cases with purely ocular muscle
      involvement, less than one half will never progress towards a more general form
      of myasthenia. However, even if they do not share the potentially life
      threatening course of generalized myasthenia, purely ocular forms are often
      responsible for severe impairment in everyday life. The diagnosis is essentially
      based on fluctuations in the time and topography of the ocular muscle weakness.
      It still remains uneasy, as investigations such as electromyography, search for
      antiacetycholine receptor antibodies (positive in 50% of cases of purely ocular
      myasthenia), and edrophonium chloride test sometimes yield false negative
      results. Whereas some patients get better while on anticholinesterasic drugs
      alone, most of them will experience insufficient improvement and need steroids
      and/or immunosuppressant drugs. There is no indication for plasma exchanges,
      intravenous immunoglobulin or thymectomy (except in the presence of thymoma).
      This treatment could well decrease the risk of an evolution towards generalized
      myasthenia. The reasons underlying the vulnerability of ocular motor muscles in
      myasthenia are complex and several factors (linked to immunology, anatomy and
      function) may combine to bring about their specific involvement. In the future,
      randomized, controlled trials will be necessary, in order to determine a more
      rational approach of the treatment of ocular myasthenia, which currently lies
      mostly on retrospective data and the expertise of reference centers implicated in
      the management of the disease.

PMID- 21075411
TI  - Descriptive spatial analysis of the cholera epidemic 2008-2009 in Harare,
      Zimbabwe: a secondary data analysis.
AB  - This ecological study describes the cholera epidemic in Harare during 2008-2009
      and identifies patterns that may explain transmission. Rates ratios of cholera
      cases by suburb were calculated by a univariate regression Poisson model and
      then, through an Empirical Bayes modelling, smoothed rate ratios were estimated
      and represented geographically. Mbare and southwest suburbs of Harare presented
      higher rate ratios. Suburbs attack rates ranged from 1.2 (95% Cl = 0.7-1.6) cases
      per 1000 people in Tynwald to 90.3 (95% Cl = 82.8-98.2) in Hopley. The
      identification of this spatial pattern in the spread, characterised by low risk
      in low density residential housing, and a higher risk in high density south west
      suburbs and Mbare, could be used to advocate for improving water and sanitation
      conditions and specific preparedness measures in the most affected areas.

PMID- 21075412
TI  - Sendai virus induced cytoplasmic actin remodeling correlates with efficient virus
      particle production.
AB  - Cytoplasmic actins have been found interacting with viral proteins and identified
      in virus particles. We analyzed by confocal microscopy the cytoplasmic beta- and
      gamma-actin patterns during the course of Sendai virus infections in polarized
      cells. We observed a spectacular remodeling of the beta-cytoplasmic actin which
      correlated with productive viral multiplication. Conversely, suppression of M
      during the course of a productive infection resulted in the decrease of particle
      production and the absence of beta-actin remodeling. As concomitant suppression
      of beta- and gamma-actins resulted as well in reduction of virus particle
      production, we propose that Sendai virus specifically induces actin remodeling in
      order to promote efficient virion production. Beta- and gamma-cytoplasmic actin
      recruitment could substitute for that of the endosomal sorting complex required
      for transport (ESCRT) mobilized by other enveloped viruses but apparently not
      used by Sendai virus.

PMID- 21075413
TI  - Estimation and characterization of PCDD/Fs and dioxin-like PCBs from Chinese iron
      foundries.
AB  - The iron foundry industry is considered to be a potential source of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). This study
      investigated the emission factors and total emission amounts of PCDD/Fs and
      dioxin-like polychlorinated biphenyls (DL-PCBs) from iron foundries in China. The
      concentrations and the World Health Organization toxicity equivalents (WHO-TEQs)
      are presented and the congener profiles are discussed in this paper. In the
      present work, 26 fly ash samples were collected and tested to quantify the
      PCDD/Fs and DL-PCBs generated by 14 plants of different scales, and five stack
      gas samples were collected from two (named as EFG and LFG) of those plants. The
      emission levels of PCDD/Fs and DL-PCBs indicated that hot-air cupolas had lower
      emissions than cold-air cupolas. When iron ore lump and sinter were used as raw
      material, the emission factors were about 250ng TEQt(-1) of product. However, if
      the raw material was scrap, the emission factors varied owing to the different
      contents of organic materials in the raw materials. It was found that the mean
      WHO-TEQ values of PCDD/Fs and DL-PCBs were 144 and 34.2pgNm(-3) in stack gas and
      20.0 and 1.58pgg(-1) in fly ash. In multiple tests, it was estimated that the
      mean emission factors of PCDD/Fs and DL-PCBs were 365 and 10.9ng WHO-TEQt(-1)
      released to residue and 2719 and 555ng TEQt(-1) released to air. The total
      emission amounts of PCDD/Fs and DL-PCBs from Chinese iron foundries with cupola
      furnaces released to residue and air were 16.8 and 146g WHO-TEQ in 2008,
      respectively.

PMID- 21075414
TI  - The influence of mariculture on mercury distribution in sediments and fish around
      Hong Kong and adjacent mainland China waters.
AB  - To study the influence of mariculture on mercury (Hg) speciation and distribution
      in sediments and cultured fish around Hong Kong and adjacent mainland China
      waters, sediment samples were collected from six mariculture sites and the
      corresponding reference sites, 200-300 m away from the mariculture sites.
      Mariculture activities increased total mercury, organic matter, carbon, nitrogen
      and sulfur concentrations in the surface sediments underneath mariculture sites,
      possibly due to the accumulation of unconsumed fish feed and fish excretion.
      However, methylmercury (MeHg) concentrations and the ratio of MeHg to THg (%
      MeHg) in sediments underneath mariculture sites were lower than the corresponding
      reference sites. The % MeHg in sediments was negatively correlated (r = -0.579, p
      < 0.05) with organic matter (OM) content among all sites, indicating that OM may
      have inhibited Hg methylation in surface sediments. Three mariculture fish
      species were collected from each mariculture site, including red snapper
      (Lutjanus campechanus), orange-spotted grouper (Epinephelus coioides) and
      snubnose pompano (Trachinotus blochii). The average MeHg concentration in fish
      muscle was 75 MUg kg-1 (wet weight), and the dietary intake of MeHg through fish
      consumption for Hong Kong residents was 0.37 MUg kg-1 week-1, which was lower
      than the corresponding WHO limits (500 MUg kg-1 and 1.6 MUg kg-1 week-1).

PMID- 21075416
TI  - VFA generation from waste activated sludge: effect of temperature and mixing.
AB  - The success of enhanced biological phosphorus removal (EBPR) depends on the
      constant availability of volatile fatty acids (VFAs). To reduce costs, waste
      streams would be a preferred source. Since VFAs were shown to vary in the
      incoming sewage and fermentate from primary sludge the next available source is
      waste activated sludge (WAS). The opportunity is particularly good in plants
      where WAS is stored before shipment. Little information is however available on
      the rate of VFA release from such sludge, especially at the lower temperatures
      and under the storage conditions typically found in colder climates. Bench-scale
      batch tests were performed to investigate the effect of temperature and
      requirement for mixing on VFA generation from WAS generated in full scale non
      EBPR wastewater treatment plant. WAS fermentation was found highly temperature
      dependent. Hydrolysis rate constant (k(h)) values of 0.17, 0.08 and 0.04 d-1 at
      24.6, 14 and 4 degrees C were obtained, respectively. Arrhenius temperature
      coefficient was calculated to be 1.07. It took 5 d to complete hydrolysis at 24.6
      degrees C, 7 d at 14 degrees C, and 9 d at 4 degrees C. The fermentation lasted
      for 20 d. At 24.6 degrees C the mixed reactor reached 84% of the overall VFA
      production only in 5 d. When temperature dropped to 14 and 4 degrees C, the ratio
      of VFA production at day 10 to overall VFA production in the mixed reactor were
      62% and 48%, respectively. The overall VFA-COD concentration in the non-mixed
      reactors was much lower than the mixed reactors. The information is important for
      the designer as there was uncertainty with the effect of temperature and mixing
      on sludge fermentation.

PMID- 21075415
TI  - Arsenic tolerances in rice (Oryza sativa) have a predominant role in
      transcriptional regulation of a set of genes including sulphur assimilation
      pathway and antioxidant system.
AB  - World wide arsenic (As) contamination of rice has raised much concern as it is
      the staple crop for millions. Four most commonly cultivated rice cultivars,
      Triguna, IR-36, PNR-519 and IET-4786, of the West Bengal region were taken for a
      hydroponic study to examine the effect of arsenate (As(V)) and arsenite (As(III))
      on growth response, expression of genes and antioxidants vis-a-vis As
      accumulation. The rice genotypes responded differentially under As(V) and As(III)
      stress in terms of gene expression and antioxidant defences. Some of the
      transporters were up-regulated in all rice cultivars at lower doses of As
      species, except IET-4786. Phytochelatin synthase, GST and gamma-ECS showed
      considerable variation in their expression pattern in all genotypes, however in
      IET-4786 they were generally down-regulated in higher As(III) stress. Similarly,
      most of antioxidants such as superoxide dismutase (SOD), ascorbate peroxidase
      (APX), guaiacol peroxidase (GPX), catalase (CAT), monodehydroascorbate reductase
      (MDHAR) and dehydroascorbate reductase (DHAR) increased significantly in Triguna,
      IR-36 and PNR-519 and decreased in IET-4786. Our study suggests that Triguna, IR
      36 and PNR-519 are tolerant rice cultivars accumulating higher arsenic; however
      IET-4786 is susceptible to As-stress and accumulates less arsenic than other
      cultivars.

PMID- 21075417
TI  - Identification of surfactants emerged in aerobic granulation.
AB  - In this study, aerobic granules were cultivated in sequencing batch reactors with
      activated sludge as the seed. The reactors were operated for 12 h per cycle with
      the organic loading rate (OLR) increasing in double stepwise from 0.5 to 4.0 g
      COD L-1d-1. Within the 40 d running, black granules with regular and smooth
      morphology were cultivated, which had high wet density and high settling
      velocity. During the granulation process, foams emerged and disappeared in the
      reactor, coinciding with the proliferation of filamentous microorganisms in the
      granules, implying that surfactants might exist and play an important role in the
      granulation. Using ultra performance liquid chromatography-tandem mass
      spectrometry, the surfactants were identified as homologous compounds of
      polyethylene glycol (PEG) with molecular weights ranging mainly from 100 to 500
      Da. Their general formulas were proposed as HO-[CH2-CH2-O](n)-H. The source of
      PEG still needs further investigation.

PMID- 21075418
TI  - Ammonium, microcystins, and hypoxia of blooms in eutrophic water cause oxidative
      stress and C-N imbalance in submersed and floating-leaved aquatic plants in Lake
      Taihu, China.
AB  - The heavy bloom of cyanobacteria is a disastrous consequence of freshwater
      eutrophication, and the bloom is highly toxic due to its secondary metabolites
      called microcystins (MCs). The release of organic substances from dense blooms
      causes an increase in NH4+ and decrease in oxygen in lake water. In the present
      study, the dynamics of physio-biochemical responses of five aquatic macrophytes
      to MCs and NH4+ stresses in Meiliang Bay were evaluated. The bay is one of the
      most seriously eutrophized areas dominated by the toxic cyanobacteria of Lake
      Taihu, China. The results demonstrate that aquatic macrophytes in Meiliang Bay
      are subjected to successive external stresses. From January to May, they are
      subjected to high NH4+ stress (>0.56 mg L(-1)), whereas from June to September or
      during dense blooms, the macrophytes experience both MC proliferation and
      moderate NH4+ toxicity (>0.3 mg L(-1)). In August, high NH4+ stress occurs along
      with hypoxia stress, whereas from September to December, the macrophytes
      experience moderate NH4+ stress, causing a serious imbalance in C-N metabolism
      and oxidative stress. Between the two aquatic plant life forms, floating-leaved
      plants are more resistant to the stresses of eutrophication than are submersed
      plants. Elevated MCs in the water column can aggravate oxidative stress and
      suppress the soluble protein contents of aquatic plants. High NH4+ in the water
      causes severe C and N imbalance in submersed macrophytes because of considerable
      carbon consumption for free amino acid synthesis. The superoxide dismutase
      activities of submersed macrophytes are suppressed by low light penetrating the
      eutrophic water, which might impair the antioxidative function of the plants. The
      findings of this study provide mainly field evidence that reveals the physical,
      chemical, and biological stresses on aquatic plants in bloom-prevailed eutrophic
      lakes.

PMID- 21075419
TI  - Phthalate exposure in pregnant women and their children in central Taiwan.
AB  - Phthalate exposure was found to be associated with endocrine disruption,
      respiratory effects, reproductive and developmental toxicity. The intensive use
      of plastics may be increasing the exposure to phthalates in Taiwanese population,
      particularly for young children. We studied phthalate metabolites in pregnant
      women and their newborns in a prospective cohort from a medical center in Central
      Taiwan. One hundred maternal urine samples and 30 paired cord blood and milk
      samples were randomly selected from all of participants (430 pregnant women).
      Eleven phthalate metabolites (MEHP, 5OH-MEHP, 2cx-MEHP, 5cx-MEPP, 5oxo-MEHP,
      MiBP, MnBP, MBzP, OH-MiNP, oxo-MiNP, and cx-MiNP) representing the exposure to
      five commonly used phthalates (DEHP, di-isobutyl phthalate (DiBP), DnBP, BBP,
      DiNP) were measured in urine of pregnant women, cord serum and breast milk after
      delivery, and in urine of their children. Exposure was estimated with excretion
      factors and correlation among metabolites of the same parent compound. Thirty and
      59 urinary samples from 2 and 5 years-old children were randomly selected from
      185 children successfully followed. Total urinary phthalate metabolite
      concentration (geometric mean, MUg L-1) was found to be higher in 2-years-olds
      (398.6) and 5-years-olds (333.7) than pregnant women (205.2). Metabolites in
      urine are mainly from DEHP. The proportion of DiNP metabolites was higher in
      children urine (4.39 and 8.31%, ages 2 and 5) than in adults (0.83%) (p<0.01).
      Compared to urinary levels, phthalate metabolite levels are low in cord blood
      (37.45) and milk (14.90). DEHP metabolite levels in women's urine and their
      corresponding cord blood are significantly correlated. Compared to other
      populations in the world, DEHP derived metabolites in maternal urine were higher,
      while phthalate metabolite levels in milk and cord blood were similar. The level
      of phthalate metabolites in milk and cord blood were comparable to those found in
      other populations. Further studies of health effects related to DEHP and DiNP
      exposure are necessary for the children.

PMID- 21075420
TI  - Alkylphenols in adipose tissues of Italian population.
AB  - Alkylphenols (APs) and AP ethoxylated compounds (APEs) were screened in human
      subcutaneous adipose tissue samples from Italy. The samples were collected during
      bariatric surgery from 16 subjects (three men and 13 women) and a total of seven
      alkylphenol compounds (APs) was detected. Nonylphenol (NP) was the compound found
      at the highest level (mean 122 ng g-1 fresh weight; range 10-266 ng g-1 fw).
      Several nonylphenol ethoxylates (NPEOs) were found in all the sample analysed
      though the frequency of detection decreased with the increasing number of
      ethoxylic groups. NP4EO was found only in four patients ranging from trace
      amounts to 41.3 ng g-1 fw. Total nonylphenols (NPEs) ranged between 45 and 1131
      ng g-1 fw, whereas the concentration of total octylphenols (OPEs) was at least 10
      times lower (range 6-80 ng g-1 fw). Our findings show that the average
      concentration of NP is about two times higher than that found in women from
      Southern Spain and up to three times that of people from Switzerland. Similarly,
      OP mean level is two times that reported in Finland and Spain populations. This
      is the first study that reports the presence of alkylphenols in the Italian
      population adipose tissue and it draws a baseline for further researches in order
      to depict a trend in human exposure to these compounds and to investigate
      possible consequences for human health.

PMID- 21075421
TI  - Life cycle toxicity assessment of pesticides used in integrated and organic
      production of oranges in the Comunidad Valenciana, Spain.
AB  - The relative impacts of 25 pesticides including acaricides, fungicides,
      herbicides, insecticides, and post-harvest fungicides, used in the production of
      oranges in Spain were assessed with current life cycle impact assessment (LCIA)
      tools. Chemical specific concentrations were combined with pesticide emission
      data and information on chemical toxicity to assess human toxicity and freshwater
      ecotoxicity impacts. As a case study, the relative impacts of two orange
      production systems in the region of Valencia, integrated pest management (IP) and
      organic production (OP), were assessed. The evaluation of active ingredients
      showed that on average acaricides have the highest human toxicity impact scores,
      while for freshwater ecotoxicity insecticides show the highest impact. In both
      impact categories the lowest impact scores were calculated for herbicides. In the
      production of 1 kg of orange fruits, where several kinds of pesticides are
      combined, results show that post-harvest fungicides can contribute more than 95%
      to the aggregate human toxicity impacts. More than 85% of aquatic ecotoxicity is
      generated by fungicides applied before harvest. The potential to reduce impacts
      on freshwater ecosystems is seven orders of magnitude, while impacts on human
      health can be reduced by two orders of magnitude. Hence, this stresses the
      importance of a careful pre-selection of active ingredients. In both impact
      categories, organic production represents the least toxic pest-control method.

PMID- 21075422
TI  - Factors responsible for rapid dissipation of acidic herbicides in the coastal
      lagoons of the Camargue (Rhone River Delta, France).
AB  - This study was aimed at investigating which processes cause acidic herbicides
      (e.g., bentazone, MCPA and dichlorprop) to rapidly disappear in the lagoons of
      the Rhone delta, which are peculiar brackish and shallow aquatic environments.
      The use of the model MASAS (Modeling of Anthropogenic Substances in Aquatic
      Systems) revealed that sorption, sedimentation, volatilization, flushing and
      abiotic hydrolysis had a minor role in the attenuation of the investigated
      herbicides. Laboratory scale biodegradation and photodegradation studies were
      conducted to better assess the significance of these two processes in the natural
      attenuation of herbicides in brackish (lagoons) waters with respect to fresh
      waters (canals draining paddy fields). Herbicide biodegradation rates were
      significantly lower in lagoon water than in canal water. Consequently,
      photodegradation was the main dissipation route of all investigated herbicides.
      The contribution of indirect photolysis was relevant for MCPA and dichlorprop
      while direct photolysis dominated for bentazone removal. There is a need to
      further investigate the identity of phototransformation products of herbicides in
      lagoons.

PMID- 21075423
TI  - Probabilistic ecological risk assessment of DDTs in the Bohai Bay based on a food
      web bioaccumulation model.
AB  - The fugacity-based food web model was developed to simulate the bioaccumulation
      of dichloro-diphenyl-trichloroethanes (DDTs) in the aquatic ecosystem in the
      Bohai Bay. The internal exposure levels (IELs) of DDTs in various organism
      categories were calculated. Monte Carlo-based uncertainty analysis was performed
      to get the of IEL distributions of DDTs in organisms. Probabilistic ecological
      risk assessment (ERA) was performed based on IEL distributions and internal
      species sensitivity distributions (SSDs). The results show that fugacities and
      bioaccumulation factors (BAFs) generally increased with increasing trophic level
      in the food web. Octanol-water partition coefficient (K(ow)), DDT levels in water
      and the lipid contents had the greatest influences on IELs in the organism
      bodies. The ecological risks of DDTs were relatively high. The risk order was
      p,p'-DDT>p,p'-DDE>p,p'-DDD. At an internal hazard quotient (HQ(int)) criterion of
      1/5, the risk probabilities were 0.10 (0.055-0.17), 0.079 (0.045-0.13) and 0.053
      (0.028-0.092) for p,p'-DDT, p,p'-DDE and p,p'-DDD, respectively. The results from
      ERA based on the internal exposure approximated those based on external exposure.
      The food web model is a feasible method to predict the extent of bioaccumulation
      and IELs of hydrophobic organic pollutants in organisms as a step to evaluate
      their risk posed on aquatic ecosystems.

PMID- 21075424
TI  - Removal of inorganic mercury and methylmercury from surface waters following
      coagulation of dissolved organic matter with metal-based salts.
AB  - The presence of inorganic mercury (IHg) and methylmercury (MeHg) in surface
      waters is a health concern worldwide. This study assessed the removal potential
      use of metal-based coagulants as a means to remove both dissolved IHg and MeHg
      from natural waters and provides information regarding the importance of Hg
      associations with the dissolved organic matter (DOM) fraction and metal
      hydroxides. Previous research indicated coagulants were not effective at removing
      Hg from solution; however these studies used high concentrations of Hg and did
      not reflect naturally occurring concentrations of Hg. In this study, water
      collected from an agricultural drain in the Sacramento-San Joaquin Delta was
      filtered to isolate the dissolved organic matter (DOM) fraction. The DOM was then
      treated with a range of coagulant doses to determine the efficacy of removing all
      forms of Hg from solution. Three industrial-grade coagulants were tested: ferric
      chloride, ferric sulfate, and polyaluminum chloride. Coagulation removed up to
      85% of DOM from solution. In the absence of DOM, all three coagulants released
      IHg into solution, however in the presence of DOM the coagulants removed up to
      97% of IHg and 80% of MeHg. Results suggest that the removal of Hg is mediated by
      DOM-coagulant interactions. There was a preferential association of IHg with the
      more aromatic, higher molecular weight fraction of DOM but no such relationship
      was found for MeHg. This study offers new fundamental insights regarding large
      scale removal of Hg at environmentally relevant regarding large-scale removal of
      Hg at environmentally relevant concentrations.

PMID- 21075425
TI  - Mixing of dust with pollution on the transport path of Asian dust--revealed from
      the aerosol over Yulin, the north edge of Loess Plateau.
AB  - Both PM(2.5) and TSP were monitored in the spring from 2006 to 2008 in an
      intensive ground monitoring network of five sites (Tazhong, Yulin, Duolun,
      Beijing, and Shanghai) along the pathway of Asian dust storm across China to
      investigate the mixing of dust with pollution on the pathway of the long-range
      transport of Asian dust. Mineral was found to be the most loading component of
      aerosols both in dust event days and non-dust days. The concentrations of those
      pollution elements, As, Cd, Pb, Zn, and S in aerosol were much higher than their
      mean abundances in the crust even in dust event days. The high concentration of
      SO(4)(2-) could be from both sources: one from the transformation of the local
      emitted SO(2) and the other from the sulfate that existed in primary dust, which
      was transported to Yulin. Na(+), Ca(2+), and Mg(2+) were mainly from the crustal
      source, while NO(3)(-) and NH(4)(+) were from the local pollution sources. The
      mixing of dust with pollution aerosol over Yulin in dust event day was found to
      be ubiquitous, and the mixing extent could be expressed by the ratio of NO(3)(
      )/Al in dust aerosol. The ratio of Ca/Al was used as a tracer to study the dust
      source. The comparison of the ratios of Ca/Al together with back trajectory
      analysis indicated that the sources of the dust aerosol that invaded Yulin could
      be from the northwestern desert in China and Mongolia Gobi.

PMID- 21075426
TI  - Correlation analysis of noise and ultrafine particle counts in a street canyon.
AB  - Ultrafine particles (UFP, diameter<100 nm) are very likely to negatively affect
      human health, as underlined by some epidemiological studies. Unfortunately,
      further investigation and monitoring are hindered by the high cost involved in
      measuring these UFP. Therefore we investigated the possibility to correlate UFP
      counts with data coming from low-cost sensors, most notably noise sensors.
      Analyses are based on an experiment where UFP counts, noise levels, traffic
      counts, nitrogen oxide (NO, NO(2) and their combination NO(x)) concentrations,
      and meteorological data were collected simultaneously in a street canyon with a
      traffic intensity of 3200 vehicles/day, over a 3-week period during summer.
      Previous reports that NO(x) concentrations could be used as a proxy to UFP
      monitoring were verified in our setup. Traffic intensity or noise level data were
      found to correlate with UFP to a lesser degree than NO(x) did. This can be
      explained by the important influence of meteorological conditions (mainly wind
      and humidity), influencing UFP dynamics. Although correlations remain moderate,
      sound levels are more correlated to UFP in the 20-30 nm range. The particles in
      this size range have indeed rather short atmospheric residence times, and are
      thus more closely short-term traffic-related. Finally, the UFP estimates were
      significantly improved by grouping data with similar relative humidity and wind
      conditions. By doing this, we were able to devise noise indicators that correlate
      moderately with total particle counts, reaching a Spearman correlation of R=0.62.
      Prediction with noise indicators is even comparable to the more-expensive-to
      measure NO(x) for the smallest UFP, showing the potential of using microphones to
      estimate UFP counts.

PMID- 21075427
TI  - Nitrogen dioxide and household fuel use in the Pakistan.
AB  - More than half the world's population use biomass fuels as a household energy
      source and, hence, face significant exposure to a number of air pollutants. In
      Pakistan about 90% of rural households and 22% of urban households use biomass
      fuels. In order to assess the levels of NO(2) in the residential micro
      environment, two sampling campaigns were carried out at different times of the
      year (summer and winter) at an urban and two rural sites during 2005 and 2007.
      Rural site I used biomass fuels while natural gas was utilized at rural site II
      and the urban site. In winter NO(2) concentrations at all three sites were higher
      in the kitchens than living rooms and outdoors. ANOVA showed that, although,
      there was a significant difference among NO(2) concentrations in the kitchens,
      living rooms and courtyards, at all the three sites, there was no significant
      different between kitchens using biomass fuels and natural gas. During the summer
      NO(2) levels fell sharply at both rural sites (from 256 MUg/m(3) and 242 MUg/m(3)
      to 51 MUg/m(3) and 81 MUg/m(3)). However at the urban site the mean levels were
      slightly higher in summer (234 MUg/m(3)) than in winter (218 MUg/m(3)). The
      considerable seasonal variation at the rural sites was due to a shift of indoor
      kitchens to open outdoor kitchens at rural site I and more ventilation at rural
      site II during summer. There was no significant difference between kitchens using
      biomass (site I) or natural gas (site II), however the kitchens at rural site II
      and urban site showed a significant difference. Overall fuel selection showed no
      significant effect on NO(2) levels. However the NO(2) concentrations may pose a
      significant threat to the health of people, especially women and children.

PMID- 21075428
TI  - The cytochrome 2C19*2 and *3 alleles attenuate response to clopidogrel similarly
      in East Asian patients undergoing elective percutaneous coronary intervention.
AB  - INTRODUCTION: Carriage of CYP2C19*2 allele is associated with diminished platelet
      response to clopidogrel. However, the loss-of-function impact of CYP2C19*3 allele
      on antiplatelet effect of clopidogrel has not been definitely verified. We
      conducted this study to compare decreased response to clopidogrel according to
      carriage of CYP2C19*2 vs. *3 allele. MATERIALS AND METHODS: The study included
      190 consecutive Korean patients undergoing elective percutaneous coronary
      intervention. Light transmittance aggregometry and the VerifyNow P2Y(12) assay
      were used to assess platelet reactivity (PR) at least 12 hours after 300-mg
      loading of clopidogrel. The cutoff of high on-treatment PR (HPR) was defined as 5
      MUmol/L ADP-induced PR >50%. CYP2C19 genotype was analyzed by the SNaPshot
      method. RESULTS: Carriers of at least one CYP2C19 variant allele were 115
      patients (60.5%), and allelic frequency of CYP2C19*2 and *3 was 30.3% and 6.8%,
      respectively. PR and the rate of HPR increased proportionally according to the
      number of CYP2C19 variant allele. Carriage of CYP2C19 variant allele was an only
      independent predictor of HPR in multivariate analysis. When we compare the effect
      of allelic carriage, there were no significant differences in platelet measures
      and the rate of HPR between carriers of CYP2C19*2 and/or *3 allele(s) whether
      they were intermediate or poor metabolizers. CONCLUSION: Carriage of CYP2C19*3
      allele is associated with diminished antiplatelet effect of clopidogrel, which
      may be as potent as the loss-of-function effect of CYP2C19*2 allele.

PMID- 21075429
TI  - Interindividual variability of in vitro response to anticoagulants.

PMID- 21075430
TI  - Platelets as immune mediators: their role in host defense responses and sepsis.
AB  - Platelets occupy a central role at the interface between thrombosis and
      inflammation. At sites of vascular damage, adherent platelets physically and
      functionally interact with circulating leukocytes. Activated platelets release
      soluble factors into circulation that may have local and systemic effects on
      blood and vascular cells. Platelets can also interact with a wide variety of
      microbial pathogens. Emerging evidence from animal models suggests that platelets
      may participate in a wide variety of processes involving tissue injury, immune
      responses and repair that underlie diverse diseases such as atherosclerosis,
      autoimmune disorders, inflammatory lung and bowel disorders, host-defense
      responses and sepsis. In this review, we summarize the general mechanisms by
      which platelets may contribute to immune function, and then discuss evidence for
      their role in host defense responses and sepsis from preclinical and clinical
      studies.

PMID- 21075432
TI  - FOXP3+ regulatory T-cells are abundant in vulvar Paget's disease and are
      associated with recurrence.
AB  - OBJECTIVE: To characterize clinical features of vulvar Paget's disease, and
      examine the quantity of immunosuppressive regulatory T-cells in vulvar Paget's
      tissue. METHODS: Vulvar Paget's cases from 1992 to 2007 from two institutions
      were identified by pathology database search. Regulatory T-cells were identified
      with FOXP3 immunohistochemistry and quantified at the dermal-epidermal junction
      using image analysis software. Thirteen non-neoplastic inflammatory cases were
      stained for comparison. RESULTS: Cases included 33 women treated for primary
      vulvar Paget's, and 7 referred at recurrence. Of the 24 primary cases with
      greater than 5 months follow-up, recurrence was documented in 12/24(50%). Eight
      women (20%) recurred multiple times, but no recurrences were invasive.
      Significantly more patients with positive margins developed recurrent disease
      (82% vs 23%, p=0.01). Secondary neoplasms occurred in 10/40(25%). FOXP3+ cells at
      the dermal-epidermal junction were quantified in 29 primary and 13 recurrent
      tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin.
      FOXP3+ cells averaged 66/HPF in primary vulvar Paget's and 66/HPF in recurrent
      Paget's, compared to 22/HPF in non-neoplastic inflammatory cases (p=0.0003,
      p=0.001). Primary cases with positive surgical margins had more FOXP3+ cells than
      those with negative margins (85 vs 49, p=0.01). Recurrent cases with positive
      margins had more FOXP3+ cells than negative cases (84 vs 33, p=0.06). FOXP3
      levels in primary specimens were higher in cases which recurred (78 vs 35,
      p=0.02). CONCLUSIONS: Increased regulatory T-cells may be associated with more
      extensive cases of vulvar Paget's disease that result in positive surgical
      margins and are associated with recurrence of disease, suggesting
      immunosuppression as a key factor.

PMID- 21075431
TI  - Platelet CD40L at the interface of adaptive immunity.
AB  - Initiated by the finding that platelets express functional CD40 ligand (CD40L,
      CD154), many new roles for platelets have been discovered in unanticipated areas,
      including the immune response. When current literature is considered as a whole,
      the picture that is emerging begins to show that platelets are able to
      significantly affect, for better or worse, the overall health and condition of
      the mammalian host. Animal models have made significant contributions to our
      expanding knowledge of platelet function, much of which is anticipated to be
      clinically relevant. While still mostly circumstantial, the evidence supports a
      critical role for CD40L in many normal and disease processes.

PMID- 21075433
TI  - Phase II study of fulvestrant in recurrent/metastatic endometrial carcinoma: a
      Gynecologic Oncology Group study.
AB  - OBJECTIVES: To evaluate the activity and toxicity of fulvestrant in advanced,
      recurrent, or persistent endometrial carcinoma. METHODS: Eligible patients with
      advanced, recurrent or persistent endometrial carcinoma not amenable to curative
      therapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4
      weeks for at least 8 weeks. Therapy was continued until evidence of progressive
      disease, or adverse effects prohibited further therapy. Response was assessed in
      patients with at least one target lesion as defined by Response Evaluation
      Criteria in Solid Tumors (RECIST) v1.0. Immunohistochemical analysis of tumor
      tissue (histology or cytology) for estrogen and progesterone receptors was
      required from the metastatic or recurrent site. RESULTS: Sixty-seven patients
      were enrolled in this study. Upon review, 14 patients were excluded. In the 22
      estrogen receptor (ER) negative patients, no patients demonstrated either a
      complete or partial response, and 4 (18%) demonstrated stable disease (as best
      response). In the 31 ER positive patients, 1 (3%), 4 (13%) and 9 (29%) patients
      demonstrated a complete, partial response, and stable disease (as best response),
      respectively. The median progression free survival and overall survival in the ER
      negative patients were 2 and 3 months and in the ER positive patients 10 and 26
      months. Treatment was well tolerated, and no patient discontinued therapy due to
      toxicity. CONCLUSIONS: Fulvestrant has minimal activity in advanced, recurrent,
      or persistent endometrial carcinoma.

PMID- 21075436
TI  - Successful management of medulloblastoma arising in an immature ovarian teratoma
      in pregnancy.

PMID- 21075434
TI  - A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy
      in endometrial cancer: a Kansai Clinical Oncology Group study (KCOG0015 trial).
AB  - OBJECTIVES: The optimal chemotherapy regimen for women with endometrial cancer
      has not been established. We assessed the feasibility, toxicity and clinical
      efficacy of combination triweekly carboplatin and weekly paclitaxel in women with
      endometrial cancer. METHODS: Eligible patients had histologically confirmed
      primary advanced or recurrent endometrial cancer (Group A), or had localized high
      risk features (Group B). All were treated with paclitaxel 80 mg/m(2) (days 1, 8
      and 15) and carboplatin AUC 5 (day 1) each 21-day cycle. A minimum of 3 cycles
      was planned; if 75% or more of patients were able to receive at least 3 cycles
      with acceptable toxicity, the regimen was declared "feasible." RESULTS: Forty
      patients were enrolled and administered 163 cycles of therapy; 38 (95%) were
      chemo-naive. No patients received radiation previously. Group A (measurable
      disease) contained 15 patients (5 with recurrent disease, 7 receiving neo
      adjuvant chemotherapy, and 3 treated adjuvantly following suboptimal
      cytoreduction). Group B (non-measurable disease) contained 25 patients (primary
      stage I:10, II:5, III:8, IV:1 and relapse 1). Hematological toxicities(G3/G4)
      were neutropenia (31%/33%) and thrombocytopenia (6%/0%). Reversible G3
      hypersensitivity (5%) and G2 cardiotoxicity (3%) was uncommon. Thirty-one
      patients (78%) completed >=3 cycles (median 4, range: 1-9). Thirteen of 15 (87%)
      measurable patients responded (3CR, 10PR). Eighty-seven percent of measurable
      patients were not progressive at 6 months. In Group A, QOL scores were
      significantly improved after 3 cycles of chemotherapy (p=0.037), and at the
      completion of chemotherapy (p=0.045). QOL scores in Group B did not change during
      therapy. CONCLUSIONS: This combination chemotherapy is feasible and effective for
      endometrial cancer patients.

PMID- 21075437
TI  - Ovarian cancer patient surveillance after curative-intent initial treatment.
AB  - OBJECTIVE: Patient surveillance after potentially curative treatment of ovarian
      carcinoma has important clinical and financial implications for patients and
      society. The optimal intensity of surveillance for these patients is unknown. We
      aimed to document the current follow-up practice patterns of gynecologic
      oncologists. METHODS: We created four idealized vignettes describing patients
      with stages I-III ovarian cancer. We mailed a custom-designed survey instrument
      based on the vignettes to the members of the Society of Gynecologic Oncologists
      (SGO). SGO members were asked, via this instrument, how often they requested 11
      discrete follow-up evaluations for their patients for the first 10 postoperative
      years after treatment with curative intent. RESULTS: We received 283 evaluable
      responses (30%) from the 943 SGO members and candidate members. The most
      frequently performed items for each year were office visit, pelvic examination,
      and serum CA-125 level. Imaging studies such as chest X-ray, abdominal-pelvic CT,
      chest CT, abdominal-pelvic MRI, and transvaginal ultrasound were rarely
      recommended. There was marked variation in the frequency of use of most tests.
      There was a decrease in the frequency of testing over time for all modalities.
      CONCLUSION: This dataset provides detailed documentation of the self-reported
      surveillance practices of highly credentialed experts who manage patients with
      ovarian cancer in the 21st century. The optimal follow-up strategy remains
      unknown and controversial. Our survey showed marked variation in surveillance
      intensity. Identifying the sources of this variation warrants further research.

PMID- 21075438
TI  - Low-dose abdominal radiation as a docetaxel chemosensitizer for recurrent
      epithelial ovarian cancer: a phase I study of the Gynecologic Oncology Group.
AB  - OBJECTIVES: The aim of this study was to determine the maximum tolerated dose and
      dose-limiting toxicity (DLT) of whole abdomen radiation as a chemosensitizer of
      weekly docetaxel for women with recurrent epithelial ovarian fallopian tube, or
      peritoneal cancers. PATIENTS AND METHODS: Women were enrolled on one of three
      dose levels of docetaxel (20, 25, or 30 mg/m(2)) administered weekly with
      concurrent low-dose whole abdominal radiation given as 60 cGy bid 2 days weekly
      for a total of 6 weeks. RESULTS: Thirteen women were enrolled and received 70
      weekly treatments of docetaxel in combination with radiation therapy. At the
      first dose level, docetaxel 25mg/m(2), grade 3 fatigue and thrombocytopenia were
      observed. At the next dose level, docetaxel 30 mg/m(2), grade 3 febrile
      neutropenia, grade 4 thrombocytopenia with epistaxis, and grade 3 diarrhea were
      observed. Given these dose-limiting toxicities, a lower dose of docetaxel
      20mg/m(2) was administered and found to be tolerable. No objective responses were
      observed among the 10 patients with measurable disease; however, the median
      progression-free survival (PFS) in all patients was 3.3 months, and 3 of the
      patients with measurable disease were free of tumor progression after 6 months
      (30%; 90% confidence interval 8.7-61%). CONCLUSIONS: Twice weekly low-dose whole
      abdomen radiation during weekly docetaxel 20 mg/m(2) was well-tolerated. Given
      the PFS demonstrated in these women with resistant ovarian cancer, further study
      of whole abdominal radiation and concurrent chemotherapy may be warranted.

PMID- 21075439
TI  - The prognostic impact of circulating proteasome concentrations in patients with
      epithelial ovarian cancer.
AB  - BACKGROUND: Intracellularly, the ubiquitin-proteasome system participates in
      crucial functions such as cell cycling, differentiation, proliferation, gene
      transcription, and apoptosis. However, in malignancies including ovarian cancer
      increased extracellular concentrations of circulating 20S proteasomes (c
      proteasomes) have been detected in blood. We tested the hypothesis that the c
      proteasome plasma concentration is a biomarker associated with the clinical
      course of ovarian cancer patients. METHODS: 20S-proteasome venous plasma
      concentration was measured by ELISA in patients presenting with ovarian cancer
      before (n=120) and after (n=68) primary treatment, and in healthy volunteers
      (n=55). The median follow-up time was 19 months. To assess the relation of
      proteasome expression with c-proteasome concentration, tumor specimens from 27
      patients were immunohistochemically stained for 20S proteasome using an antibody
      directed against the core subunits of the catalytic domain of the 20S proteasome.
      RESULTS: Median c-proteasome concentration was higher (p<0.0001) in untreated
      ovarian cancer patients (457.5 ng/ml, range: 200-12540 ng/ml) than in healthy
      controls 290 ng/ml, range: 140-425 ng/ml). Following completion of primary
      treatment, the median c-proteasome concentration increased (p=0.003) relative to
      baseline (595 ng/ml, range: 200-20000 ng/ml) and concentrations positively
      correlated (p=0.031) with residual disease left at primary surgery. Patients with
      post-treatment c-proteasome concentrations exceeding the cohort's median showed a
      diminished survival (p=0.045). We found no correlation between c-proteasome
      concentration and strength of proteasomal staining in tumor specimens.
      CONCLUSIONS: Circulating proteasome concentrations correlate with residual tumor
      mass and might be a prognostic variable in ovarian cancer following primary
      therapy.

PMID- 21075441
TI  - The Asthma Predictive Index: not a useful tool in clinical practice.

PMID- 21075440
TI  - A new index of priority symptoms in advanced ovarian cancer.
AB  - OBJECTIVE: This study sought to develop and examine preliminary validity of the
      NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), a new ovarian cancer-specific
      symptom index comprised of symptoms rated as highest priority by both oncology
      clinical experts and women with advanced ovarian cancer. METHODS: Fifty-one women
      with advanced ovarian cancer rated the importance of 30 symptoms associated with
      advanced ovarian cancer. Ten gynecologic oncologists then rated symptoms
      according to whether they were predominantly disease- or treatment-related.
      Patient priorities were then reconciled with previously-published clinician
      priorities for symptom measurement in ovarian cancer. This produced the NFOSI-18.
      Participants also completed measures of quality of life and performance status to
      examine preliminary validity of the NFOSI-18. RESULTS: An 18-item symptom index
      for advanced ovarian cancer was developed, including three subscales: disease
      related symptoms, treatment-related symptoms, and general function/well-being.
      Lower NFOSI-18 scores indicate greater high-priority symptom burden. Preliminary
      reliability suggests good internal consistency (alpha=0.80). The NFOSI-18 and its
      subscales were significantly positively associated with quality of life validity
      criteria. Scores on the NFOSI-18 differed significantly by performance status,
      with poor performance status associated with lower NFOSI-18 scores. CONCLUSIONS:
      The NFOSI-18 shows preliminary evidence for reliability and validity as a brief
      assessment of the most important symptoms associated with treatment for advanced
      ovarian cancer.

PMID- 21075442
TI  - The dimensional stability of impression materials and its effect on in vitro
      tooth wear studies.
AB  - OBJECTIVES: To assess the dimensional stability of 8 impression materials over 12
      weeks relevant to in vitro tribology studies. METHODS: Ten impressions from eight
      impression materials were taken of a metal block (ADA block) conforming to the
      American Dental Association specification for impression materials and of another
      metal block (custom block) which allowed measurements over a larger surface area.
      The impressions and blocks were scanned on a non-contacting laser profilometer
      (Taicaan(r) - Southampton, UK) and using surface metrology software Boddies(r)
      (Taicaan(r) - Southampton, UK) measurements were made at 24h, 2, 4, 8 and 12
      weeks. The impression materials tested were [1] Aquasil(r), [2] Aquasil(r) DECA,
      [3] Affinis(r), [4] Express(r), [5] Extrude(r), [6] Impregum(r), [7] President(r)
      and [8] Take 1(r). RESULTS: Seven addition silicones and one polyether [6] were
      tested. [2] and [6] were monophasic, the rest were putty-wash. The results from
      impressions of the ADA block showed that all materials contracted compared to
      measurements obtained directly from the block [1] expanded over time (+31.5 MUm)
      (p<0.05). The results from the custom block showed that all materials contracted
      compared to direct measurements of the block. [4] and [7] expanded over time (+62
      MUm and +63.8 MUm respectively). [8] contracted over time (-54.7 MUm) (p<0.05).
      SIGNIFICANCE: No material showed linear changes >1.5% and were stable for 12
      weeks. Nevertheless, the range of changes would affect tribology studies were cut
      offs lesser than the reported changes are selected. All impressions should be
      processed after similar time delays to reduce the errors introduced by
      dimensional changes.

PMID- 21075443
TI  - Degradation of polymeric restorative materials subjected to a high caries
      challenge.
AB  - OBJECTIVES: The aim of this study was to evaluate the degradation of different
      resin filling materials after a caries challenge, by high performance liquid
      chromatography (HPLC) and contact angle (theta) measurement. METHODS: Four
      different polymeric restorative materials (a resin composite, a polyacid-modified
      resin composite, an ormocer and a resin-modified glass ionomer cement) were
      tested. Five samples (30 mm * 6 mm * 2 mm) of each material were formed in a
      Teflon mold, following the manufacturer's instructions. After pH cycles, the
      solutions were injected in an HPLC. The theta was obtained, before and after pH
      cycle, by a goniometer at 60% air humidity and 25 degrees C. A distilled water
      drop (0.006 ml) was put on the material surface, and after 6 min, 10 measures
      were obtained at 20s intervals. Each sample received 4 drops, one at a time, on
      different areas. RESULTS: HPLC results showed elution of byproducts in all
      materials. This was greater in the acid medium. Bis-GMA and TEGDMA were detected
      in TPH Spectrum and Definite residues. Analyses of the contact angle by ANOVA and
      Student-Neuman-Keuls's test showed that the surfaces of TPH Spectrum, Dyract AP
      and Definite were altered, except Vitremer (p<0.05). SIGNIFICANCE: All materials
      tested degraded on a caries simulated medium, suggesting that a great effort
      should be made to disseminate oral health information, since a high caries
      challenge environment (low pH) can lead to dental composite degradation, with
      potential toxic risks to patients.

PMID- 21075445
TI  - What do children die from in India today?

PMID- 21075444
TI  - Causes of neonatal and child mortality in India: a nationally representative
      mortality survey.
AB  - BACKGROUND: More than 2.3 million children died in India in 2005; however, the
      major causes of death have not been measured in the country. We investigated the
      causes of neonatal and child mortality in India and their differences by sex and
      region. METHODS: The Registrar General of India surveyed all deaths occurring in
      2001-03 in 1.1 million nationally representative homes. Field staff interviewed
      household members and completed standard questions about events that preceded the
      death. Two of 130 physicians then independently assigned a cause to each death.
      Cause-specific mortality rates for 2005 were calculated nationally and for the
      six regions by combining the recorded proportions for each cause in the neonatal
      deaths and deaths at ages 1-59 months in the study with population and death
      totals from the United Nations. FINDINGS: There were 10,892 deaths in neonates
      and 12,260 in children aged 1-59 months in the study. When these details were
      projected nationally, three causes accounted for 78% (0.79 million of 1.01
      million) of all neonatal deaths: prematurity and low birthweight (0.33 million,
      99% CI 0.31 million to 0.35 million), neonatal infections (0.27 million, 0.25
      million to 0.29 million), and birth asphyxia and birth trauma (0.19 million, 0.18
      million to 0.21 million). Two causes accounted for 50% (0.67 million of 1.34
      million) of all deaths at 1-59 months: pneumonia (0.37 million, 0.35 million to
      0.39 million) and diarrhoeal diseases (0.30 million, 0.28 million to 0.32
      million). In children aged 1-59 months, girls in central India had a five-times
      higher mortality rate (per 1000 livebirths) from pneumonia (20.9, 19.4-22.6) than
      did boys in south India (4.1, 3.0-5.6) and four-times higher mortality rate from
      diarrhoeal disease (17.7, 16.2-19.3) than did boys in west India (4.1, 3.0-5.5).
      INTERPRETATION: Five avoidable causes accounted for nearly 1.5 million child
      deaths in India in 2005, with substantial differences between regions and sexes.
      Expanded neonatal and intrapartum care, case management of diarrhoea and
      pneumonia, and addition of new vaccines to immunisation programmes could
      substantially reduce child deaths in India. FUNDING: US National Institutes of
      Health, International Development Research Centre, Canadian Institutes of Health
      Research, Li Ka Shing Knowledge Institute, and US Fund for UNICEF.

PMID- 21075446
TI  - Genome-wide expression profile of first trimester villous and extravillous human
      trophoblast cells.
AB  - We have examined the transcriptional changes associated with differentiation from
      villous to extravillous trophoblast using a whole genome microarray. Villous
      trophoblast (VT) is in contact with maternal blood and mediates nutrient exchange
      whereas extravillous trophoblast (EVT) invades the decidua and remodels uterine
      arteries. Using highly purified first trimester trophoblast we identified over
      3000 transcripts that are differentially expressed. Many of these transcripts
      represent novel functions and pathways that show co-ordinated up-regulation in VT
      or EVT. In addition we identify new players in established functions such as
      migration, immune modulation and cytokine or angiogenic factor secretion by EVT.
      The transition from VT to EVT is also characterised by alterations in
      transcription factors such as STAT4 and IRF9, which may co-ordinate these
      changes. Transcripts encoding several members of the immunoglobulin-superfamily,
      which are normally expressed on leukocytes, were highly transcribed in EVT but
      not expressed as protein, indicating specific control of translation in EVT.
      Interactions of trophoblast with decidual leukocytes are involved in regulating
      EVT invasion. We show that decidual T-cells, macrophages and NK cells express the
      inhibitory collagen receptor LAIR-1 and that EVT secrete LAIR-2, which can block
      this interaction. This represents a new mechanism by which EVT can modulate
      leukocyte function in the decidua. Since LAIR-2 is detectable in the urine of
      pregnant, but not non-pregnant women, trophoblast-derived LAIR-2 may also have
      systemic effects during pregnancy.

PMID- 21075447
TI  - Maternal gene expression profiling during pregnancy and preeclampsia in human
      peripheral blood mononuclear cells.
AB  - Preeclampsia is a major obstetrical complication affecting maternal and fetal
      health. While it is clear that there is a substantial placental contribution to
      preeclampsia pathogenesis, the maternal contribution is less well characterized.
      We therefore performed a genome-wide transcriptome analysis to explore disease
      associated changes in maternal gene expression patterns in peripheral blood
      mononuclear cells (PBMCs). METHODS: Preeclampsia was defined as gestational
      hypertension, proteinuria and hyperurecimia. Total RNA was isolated from PBMCs
      obtained from women with uncomplicated pregnancies (n = 5) and women with
      preeclamptic pregnancies (n = 5). Gene expression analysis was carried out using
      Agilent oligonucleotide microarrays. Biological pathway analysis was undertaken
      using Ingenuity Pathway Analysis software. Quantitative real-time PCR (QRTPCR)
      was performed to validate the gene expression changes of selected genes in
      normotensive and preeclamptic patients (n = 12 each). RESULTS: We identified a
      total of 368 genes that were differentially expressed in women with preeclampsia
      compared to normal controls with false discovery rate (FDR) controlled at 10%. In
      follow up experiments we further analyzed the expression levels of a number of
      genes that were identified as altered by the microarray data including survivin
      (BIRC5), caveolin (CAV1), GATA binding protein-1 (GATA1), signal tranducer and
      activator of transcription 1 (STAT1), E2F transcription factor-1 (E2F1),
      fibronectin-1 (FN1), interleukin-4 (IL-4), matrix metalloprotease-9 (MMP-9) and
      WAP four disulfide domain protein (WFDC-1) by QRTPCR. Additionally we performed
      immuno blot analysis and zymography to verify some of these candidate genes at
      the protein level. Computational analysis of gene function identified an anti
      proliferative and altered immune function cellular phenotype in severe
      preeclamptic samples. CONCLUSIONS: We have characterized the genome-wide mRNA
      expression changes associated with preeclampsia-specific genes in circulating
      maternal blood cells at the time of delivery. In addition to providing
      information relating to the biological basis of the preeclampsia phenotype, our
      data provide a number of potential biomarkers for use in the further
      characterization of this disease.

PMID- 21075448
TI  - The type III inositol 1,4,5-trisphosphate receptor is associated with
      aggressiveness of colorectal carcinoma.
AB  - The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca(2+) signaling in
      epithelia and regulates cellular functions such as secretion, apoptosis and cell
      proliferation. Loss of one or more InsP3R isoform has been implicated in disease
      processes such as cholestasis. Here we examined whether gain of expression of
      InsP3R isoforms also may be associated with development of disease. Expression of
      all three InsP3R isoforms was evaluated in tissue from colorectal carcinomas
      surgically resected from 116 patients. Type I and II InsP3Rs were seen in both
      normal colorectal mucosa and colorectal cancer, while type III InsP3R was
      observed only in colorectal cancer. Type III InsP3R expression in the advancing
      margins of tumors correlated with depth of invasion, lymph node metastasis, liver
      metastasis, and TNM stage. Heavier expression of type III InsP3R also was
      associated with decreased 5-year survival. shRNA knockdown of type III InsP3R in
      CACO-2 colon cancer cells enhanced apoptosis, while over-expression of the
      receptor decreased apoptosis. Thus, type III InsP3R becomes expressed in colon
      cancer, and its expression level is directly related to aggressiveness of the
      tumor, which may reflect inhibition of apoptosis by the receptor. These findings
      suggest a previously unrecognized role for Ca(2+) signaling via this InsP3R
      isoform in colon cancer.

PMID- 21075449
TI  - Plant high tolerance to excess manganese related with root growth, manganese
      distribution and antioxidative enzyme activity in three grape cultivars.
AB  - The cuttings of grape (Vitis vinifera Linn.) were exposed to Hoagland's solution
      containing five different manganese (Mn) concentrations to investigate Mn
      toxicity and the possible detoxifying responses. Three genotypes (i.e. cultivars
      Combiner, Jingshou and Shuijing) were used in present study. The results showed
      that grape species is highly tolerant to excess Mn. The plant growth is
      stimulated by as high as 15 or 30 mM Mn, and then depressed by higher Mn levels.
      The grape tolerance to excess Mn is related with plant capacity to keep constant
      or increased root growth as well as to keep high root activity. Also, the grape
      could employ some effective but intraspecific strategies to detoxify cellular Mn
      stress by excluding excess Mn out of leaf tissues or by enhancing antioxidative
      capacity. On the other hand, the present study showed that there existed
      different (or contrast) distribution pattern for excess Mn in grape. Majority of
      Mn was transferred and accumulated in the above-ground part in Combiner while
      Jingshou stored most Mn in root systems. For the first time our result showed the
      extreme tolerance and contrast performance at Mn translocation in an important
      fruit species with revealed genomic information.

PMID- 21075450
TI  - What can we learn from monitoring PCBs in the European eel? A Belgian experience.
AB  - Between 2000 and 2007 pooled muscle tissue samples of the European eel (Anguilla
      anguilla) from 48 sites in Flanders (Belgium) were analysed for 30
      polychlorinated biphenyl (PCB) congeners. There was a large variation between
      individual sites (range 11-7752 ng/g wet weight (ww) for the sum of the ICES 7
      PCBs), eels from the River Meuse basin (mean 1545 ng/g ww) being considerably
      more polluted than those from the River Scheldt (615) and IJzer (61) basins.
      Overall, PCB 153, PCB 138 and PCB 180 were the most prominent congeners, however
      PCB patterns varied between the monitored locations. Analysis of the weight
      percentage of congeners demonstrates obvious differences in PCB composition
      between sites, indicating differential sources of pollution. Due to the variation
      in patterns, atmospheric fallout does not seem to be the main source of the PCB
      spread, but instead both local and upstream sources linked to industrial
      activities seem to be the main cause for PCB presence in Flanders. Considering
      the levels of the Sum 7 PCBs, eels are not compliant with the Belgian legal
      limits for consumption (75 ng/g ww) in 71% of the sites. Regular consumption of
      eels from polluted sites leads to a considerable excess of the WHO Acceptable
      Daily Intake value. Consumption of wild eels should by all means be prevented, as
      it presents risks for human health, especially for local anglers consuming their
      catch.

PMID- 21075451
TI  - The psychometric properties of the panic disorder module of the Patient Health
      Questionnaire (PHQ-PD) in high-risk groups in primary care.
AB  - AIMS: To study the validity of detecting panic disorder (PD) using the Patient
      Health Questionnaire (PHQ) in a high-risk population in primary care and to test
      whether modified evaluation algorithms improve the operating characteristics of
      this questionnaire. Furthermore, the influence of psychiatric comorbidity on the
      test characteristics of the panic module was studied. METHODS: The PHQ was
      administered in a primary care sample with patients at high-risk for psychiatric
      disorders. The total sample of 479 high-risk patients comprised 311 frequent
      attenders (FA), 39 patients with unexplained somatic complaints (USC) and 191
      patients with mental health problems (MHP). The Structured Clinical Interview for
      DSM-IV Axis I Disorders (SCID- I) was the reference standard for the presence of
      PD. Sensitivity, specificity, and predictive values were calculated. The
      conditional test characteristics were calculated based on the observed prevalence
      of PD in the three high-risk groups. RESULTS: PD was diagnosed in 4.8% of the
      FAs, in 9.8% of the USCs and in 7.6% of the MHPs. The PHQ achieved moderate
      operating characteristics. Modified evaluation algorithms of the questionnaire
      led to an improvement of test characteristics, especially the screening question:
      sensitivity .71 and specificity .83. Psychiatric comorbidity increased
      sensitivity while decreasing specificity. CONCLUSION: The original and modified
      algorithms of the PHQ-PD performed moderately in screening for panic disorder.
      Using only the first question of the PHQ-PD showed the best psychometric
      properties (sensitivity). For screening purposes requiring high sensitivity we
      endorse to use the screening question instead of the original algorithm.

PMID- 21075452
TI  - Bright light treatment of depressive symptoms in patients with restrictive type
      of anorexia nervosa.
AB  - BACKGROUND: Light therapy refers to two different categories of treatment. One of
      them is used in common medical practice and the other in complementary medicine.
      The aim of the study was to assess the effect of short time (6 weeks) bright
      light treatment (BLT) on depressive symptoms in female patients with the
      restrictive type of anorexia nervosa (AN-R). METHODS: Twenty-four girls, aged 15
      20 (mean 17.4+/-1) years, diagnosed as AN-R, with concomitant depressive symptoms
      >=17 points on the 21-item Hamilton Depression Rating Scale (HDRS) were studied.
      All girls received cognitive behavioral therapy. Among them, twelve were randomly
      assigned to additional treatment with BLT for 6 weeks (10,000 lux, 30 min daily).
      Both groups did not differ on baseline demographic and clinical parameters. The
      assessments of depression by means of HDRS and measuring of body mass index (BMI)
      were done weekly throughout the treatment. RESULTS: Improvement of depression was
      significantly greater in the group receiving BLT, with a significant difference
      between groups in depression intensity after 5 and 6 weeks. There was no
      difference in the increase of BMI between groups after 6 weeks, although such
      increase started earlier in patients treated with BLT. LIMITATIONS: Six weeks of
      treatment may be an insufficient duration to draw the conclusion about the
      efficacy of BLT and a follow-up is needed to assess the maintenance of the
      effect. CONCLUSIONS: The results obtained may suggest that BLT could be an
      effective non-pharmacological modality for the treatment of depression in
      patients with AN-R.

PMID- 21075453
TI  - Cognitive effects of six months of treatment with quetiapine in antipsychotic
      naive first-episode schizophrenia.
AB  - Effects of quetiapine on cognition were assessed in a group of first-episode
      antipsychotic-naive patients with schizophrenia (N=24). A comprehensive battery
      of neuropsychological tests was administered at baseline and after 6 months of
      treatment with quetiapine. In order to examine retest effects, a matched healthy
      control group (N=24) was also tested at baseline and after 6 months. Only few
      differential changes were observed between patients and healthy controls. Of 8
      cognitive domains examined, only significant changes in executive function
      suggested possible ameliorating effects of quetiapine. Patients also improved on
      speed of processing; however, this was parallel to the retest effects found in
      healthy controls. When covaried for differences at baseline, patients showed
      smaller improvements in speed of processing than the retest effects found in
      controls, as well as a lack of retest effects on sustained attention and working
      memory that were found in healthy controls. The main result of the study is that
      there was very little evidence of efficacy of quetiapine on cognition. The study
      also indicated a lack of normal retest effects in patients compared to controls.

PMID- 21075454
TI  - Affective reactivity in heroin-dependent patients with antisocial personality
      disorder.
AB  - The Antisocial personality disorder (ASPD), one of the most common co-morbid
      psychiatric disorders in heroin-dependent patients, is associated with a lack of
      affective modulation. The present study aimed to compare the affect-modulated
      startle responses of opioid-maintained heroin-dependent patients with and without
      ASPD relative to those of healthy controls. Sixty participants (20 heroin
      dependent patients with ASPD, 20 heroin-dependent patients without ASPD, 20
      healthy controls) were investigated in an affect-modulated startle experiment.
      Participants viewed neutral, pleasant, unpleasant, and drug-related stimuli while
      eye-blink responses to randomly delivered startling noises were recorded
      continuously. Both groups of heroin-dependent patients exhibited significantly
      smaller startle responses (raw values) than healthy controls. However, they
      showed a normal affective modulation: higher startle responses to unpleasant,
      lower startle responses to pleasant stimuli and no difference to drug-related
      stimuli compared to neutral stimuli. These findings indicate a normally modulated
      affective reactivity in heroin-dependent patients with ASPD.

PMID- 21075455
TI  - Group versus individual cognitive treatment for Obsessive-Compulsive Disorder:
      changes in non-OCD symptoms and cognitions at post-treatment and one-year follow
      up.
AB  - Current cognitive approaches postulate that obsessions and compulsions are caused
      and/or maintained by misinterpretations about their meaning. This assumption has
      led to the development of cognitive therapeutic (CT) procedures designed to
      challenge the dysfunctional appraisals and beliefs patients have about their
      obsessions. Nonetheless, few studies have compared the efficacy of individual and
      group CT in changing the dysfunctional cognitions that hypothetically underlie
      Obsessive-Compulsive Disorder (OCD). In this study, 44 OCD patients were assigned
      to individual (n=18) or group (n=24) CT. Sixteen completed the individual CT, and
      22 completed the group CT. The effects of the two CT conditions on depression and
      worry tendencies were comparable. Individual treatment was more effective than
      group treatment in decreasing scores on dysfunctional beliefs (responsibility,
      overestimation of threat, and intolerance to uncertainty) and the use of
      suppression as a thought control strategy. The post-treatment changes were
      maintained one year later. The correlations between symptom improvement (OCD
      severity change) and belief changes were moderate: in the individual treatment
      the greatest associations were with beliefs about thoughts (importance and
      control), whereas in the group treatment the greatest associations were with
      beliefs related to anxiety in general (threat overestimation and intolerance to
      uncertainty).

PMID- 21075456
TI  - Porcine blood mononuclear cell cytokine responses to PAMP molecules: comparison
      of mRNA and protein production.
AB  - Pathogen-associated molecular patterns (PAMPs) are conserved molecules of
      microorganisms inducing innate immune cells to secrete distinct patterns of
      cytokines. In veterinary species, due to a lack of specific antibodies, cytokines
      are often monitored as expressed mRNA only. This study investigated the induction
      of IFN-alpha, IL-12 p40, IL-1beta, TNF-alpha, IL-6 and IL-10 by PAMP-molecules
      [CpG oligonucleotide D19 (CpG), peptidoglycan (PGN), lipopolysaccharide (LPS),
      Pam(3)Cys and poly-U] in porcine blood mononuclear cells (BMC) within a 24 h
      period. As expected, cytokine responses were PAMP-specific, CpG inducing IFN
      alpha and IL-12 p40, and PGN, LPS and Pam(3)Cys inducing varying amounts of IL-12
      p40, IL-1beta, TNF-alpha, IL-6 and IL-10. Surprisingly, the ssRNA-mimic poly-U
      induced IL-6 and IL-1beta only. Using CpG, PGN and LPS, the kinetics of cytokine
      production measured as mRNA (reverse transcription (RT)-qPCR) and protein
      (ELISA), respectively, correlated well, mRNA responses preceding protein
      responses. With the exception of IL-1beta and IL-6, mRNA-responses were
      transient, whereas protein responses, except for TNF-alpha, followed saturation
      kinetics. Remarkably, LPS-induced TNF-alpha mRNA was not followed by a protein
      response. These results provide guidelines concerning the timing and use of
      protein and mRNA determinations for the characterization of porcine cytokine
      responses to PAMPs, although given the low number of animals used here results
      are preliminary and need confirmation in a larger study.

PMID- 21075458
TI  - Oxidative stress may mediate association of stereotypy and immunity in autism, a
      novel explanation with clinical and research implications.

PMID- 21075459
TI  - Importance of the extracellular loops in G protein-coupled receptors for ligand
      recognition and receptor activation.
AB  - G protein-coupled receptors (GPCRs) are the major drug target of medicines on the
      market today. Therefore, much research is and has been devoted to the elucidation
      of the function and three-dimensional structure of this large family of membrane
      proteins, which includes multiple conserved transmembrane domains connected by
      intra- and extracellular loops. In the last few years, the less conserved
      extracellular loops have garnered increasing interest, particularly after the
      publication of several GPCR crystal structures that clearly show the
      extracellular loops to be involved in ligand binding. This review will summarize
      the recent progress made in the clarification of the ligand binding and
      activation mechanism of class-A GPCRs and the role of extracellular loops in this
      process.

PMID- 21075457
TI  - Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain
      in PBMCs from MS patients.
AB  - Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin
      specific T cells into the central nervous system (CNS). During active disease,
      pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells.
      Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory
      cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs)
      activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO
      gene expression in MS PBMCs, which was markedly decreased in calpain expressing
      cells. Functional assay showed that incubation of MS patient PBMCs with calpain
      inhibitor or recombinant IDO attenuates T cell proliferation. These results
      suggest that calpain inhibition may attenuate MS pathology and augment the
      efficacy of standard immunomodulatory agents used to treat this disease.

PMID- 21075460
TI  - Replicability and reliability of pain assessment forms in geriatrics.
AB  - Aim of the study was to investigate the replicability and reliability of the
      multi-dimensional health assessment questionnaire (MDHAQ) and visual analog scale
      (VAS) in young and elderly individuals with chronic pain. Ambulatory patients, 20
      of them aged above 65 years and complaining about chronic pain and 20 patients
      with the age of 40 and younger working in a factory were assessed with VAS and
      MDHAQ. The assessment was repeated to investigate the replicability and
      reliability of both tests. According to MDHAQ disability index (DI), the elderly
      had more complains on the first and second day of the study (p<0.001). In terms
      of changes between first and second days, DI scores of the elderly group
      (r=0.634; p=0.003) and the younger group (r=0.888; p<0.001) had quite similar
      responses. Criteria for the assessment of pain, fatigue and general condition
      according to MDHAQ were similar in both groups in terms of changes between first
      and second day of the study, there was no significant differences between the
      groups. But while responses in the younger group according to these 3 parameters
      were highly reliable, the elderly group's responses were reliable only for their
      last week pain assessment. Both tests were replicable in the elderly group, VAS
      and MDHAQ were especially applicable for the last time phase of their pain; while
      fatigue, general health condition and DI indicated diminished reliability in the
      elderly group, compared to the young group.

PMID- 21075461
TI  - A Turkish version of Kogan's attitude toward older people (KAOP) scale:
      reliability and validity assessment.
AB  - The considerable growth in the elderly population in Turkey has brought with it
      problems as well as concerns regarding gerontological education for health care
      professionals. The quality of care provided for older people is directly related
      to the attitudes of health care professionals. Validated instruments are needed
      in order to study attitudes toward old people. Aim of this study was to assess
      the reliability and validity of a Turkish version of KAOP among faculty of health
      sciences (health management, nutrition and dietetics, nursing, physical therapy,
      social workers and sports) students (n=594) at a university. The scale was
      translated using the back-translation technique. A two-phase data collection
      design was used. Four weeks following the first completion, another KAOP form was
      given. Content validity, construct validity, internal consistency, and stability
      reliability were assessed. Scores were between 86 and 175. The study sample
      reported slightly positive attitudes (132.9 +/- 14.74). All of the 34 items were
      found to have significant item-to-total correlations. The content validity index
      was 0.94. The Cronbach's alpha was 0.84 for the total scale. The Turkish version
      of the KAOP can be considered reliable and valid scale for assessing the
      attitudes toward older people.

PMID- 21075462
TI  - Association between executive function and physical performance in older Korean
      adults: findings from the Korean Longitudinal Study on Health and Aging (KLoSHA).
AB  - Reduced executive function and physical performance are common age-related
      conditions. This study evaluated the associations between executive function and
      physical performance in a representative sample of older adults. Cross-sectional
      data were analyzed from a population-based sample of 629 men and women aged 65 or
      older and living in one typical city in Korea. Specific aspects of executive
      function were assessed using the trail making test, digit span test, and lexical
      fluency test to measure set shifting, working memory and cognitive flexibility
      functions. Physical performance was measured using performance-oriented mobility
      assessment (POMA) scores and isokinetic muscle strength. Subjects' self-efficacy
      was also assessed using the activities-specific balance confidence (ABC) scale.
      Results of the lexical fluency test were associated with POMA scores and muscle
      strength, independent of age, gender, education, comorbidity, physical activity
      status, depression, and global cognition, suggesting that reduced cognitive
      flexibility is associated with reduced physical performance and muscle strength.
      Self-efficacy was also independently associated with physical performance and
      muscle strength. Clinicians need to consider the association between executive
      function and physical performance when working to improve physical functioning in
      an aged population.

PMID- 21075463
TI  - Outcome predictors of initial treatment with topical lubricant and parafunctional
      habit control in burning mouth syndrome (BMS).
AB  - Burning mouth syndrome (BMS) is a common chronic pain condition which mainly
      affects elderly women. The concomitant prescription of topical lubricants with
      oral parafunctional habit control has been reported as an effective initial
      approach for patients with BMS. In this study, we have investigated outcome
      predictors of this initial treatment in patients with BMS. One hundred forty
      patients with BMS (12 men and 128 women, mean age 59.9+/-10.7 years) were
      instructed to avoid oral parafunctions and to use topical lubricant for 2 weeks.
      The patients were sub-grouped according to psychological status, salivary flow
      rate, presence of psychiatric medications, symptom area and duration, symptom
      severity, presence of oral parafunctions, and accompanying oral complaints. The
      changes in symptoms were analyzed and compared between sub-groups. Subjects with
      T-scores<=50 for each psychological symptom dimension, a flow rate of stimulated
      whole saliva (SWS)>0.5 ml/min, no psychiatric medications, and a greater degree
      of initial symptoms (VAS>=5) displayed greater decreases in symptoms compared
      with their counterparts. In conclusion, psychological status, psychiatric
      medications, flow rate SWS, and initial symptom severity can be outcome
      predictors of the initial treatment approach for patients with BMS.

PMID- 21075464
TI  - Comparison of psychological symptoms in post-cryptogenic cerebral-vascular
      accident (CVA) and/or transient ischemic attack (TIA) patients who have undergone
      foramen ovale closure, and in post-CVA patients.
AB  - The patent foramen ovale (PFO) is a controversial risk factor for CVA or TIA. In
      our center, adult PFO patients diagnosed with post cryptogenic CVA/TIA undergo
      trans-catheter closure of the PFO to decrease the risk of recurrent stroke. The
      aim of the study was to compare levels of functioning, depression and anxiety in
      post PFO closure patients following cryptogenic CVA/TIA and in other patients
      post CVA/TIA without PFO. Eighty-nine patients who had undergone trans-catheter
      PFO closure and 56 non-PFO post-CVA patients completed demographic, functioning,
      anxiety and depression questionnaires. Additional medical data were recorded from
      the medical files. Patients who had undergone trans-catheter PFO closure post CVA
      or TIA reported better level of functioning and substantially lower levels of
      depression and anxiety. The 70% of depression and 55% of anxiety variances were
      explained by female gender, older age, lower education, lower functioning level
      and additional health problems. Functioning level was the strongest contributor
      to the explained variance of psychological symptoms. We conclude that patients
      who have undergone trans-catheter PFO closure following cryptogenic CVA/TIA,
      which may prevent stroke recurrence, show good functioning and low levels of
      psychological symptoms. The procedure helps to keep these patients in a good
      physical and psychological health.

PMID- 21075465
TI  - Rationale and design of a study to evaluate effects of pitavastatin on Japanese
      patients with chronic heart failure: the pitavastatin heart failure study (PEARL
      study).
AB  - BACKGROUND: HMG-CoA reductase inhibitors (statins) are known to have pleiotropic
      effects in addition to their lipid-lowering effect. Many studies have suggested
      cardioprotective effects of statins, however, recent large-scale clinical trials
      using rosuvastatin, a hydrophilic statin, have failed to show beneficial effects
      on cardiovascular events in patients with severe heart failure. We have designed
      the study to evaluate the effects of pitavastatin, a lipophilic statin, on
      Japanese patients with mild to moderate heart failure. METHODS AND RESULTS: Five
      hundred seventy-seven patients with chronic heart failure were enrolled. We used
      a prospective, randomized, open-label, and blinded-endpoint evaluation (PROBE)
      design. Patients aged 20-79 years old with symptomatic (NYHA functional class II
      or III) heart failure and a left ventricular ejection fraction of <= 45% were
      randomly allocated to either receive pitavastatin (2mg/day) or not in addition to
      conventional therapy for heart failure by using the minimization method. Follow
      up will be continued until March 2011. The primary endpoint is a composite of
      cardiac death and hospitalization for worsening heart failure. CONCLUSIONS: The
      PEARL study will provide important data on the role of pitavastatin in the
      treatment of Japanese patients with mildly symptomatic heart failure (UMIN-ID:
      UMINC000000428).

PMID- 21075466
TI  - MRSA CC398 in the pig production chain.
AB  - In 2005, a distinct clone of methicillin resistant Staphylococcus aureus (MRSA
      CC398) was found in pigs and people in contact with pigs. The structure of the
      pig production chain in high technology pig husbandry enables pathogens to spread
      during animal trading, with an increasing prevalence in herds further down the
      chain. The objective of this study was to quantify the effect of the MRSA status
      of the supplying herd on the MRSA status of the receiving herd in order to gain
      more insight into the role of animal trading as a transmission route for MRSA
      CC398. Nasal samples (60-80 pigs per herd) were collected from 38 herds; in 20
      herds, environmental samples were collected as well. Ten MRSA-positive herds
      (based on the results of nasal swabs of 10 individual pigs per herd) from a prior
      study were included in the data analysis. Herds were classified as MRSA positive
      if at least one sample tested positive. The 48 herds were part of 14 complete (40
      herds) and 4 incomplete (8 herds) pig production chains. Fifty-six percent of the
      herds were classified as MRSA positive. MRSA-positive herds were observed at the
      start (breeding herds), middle (farrowing herds) and the end (finishing herds) of
      the pig production chain. All of the herds in 8 chains tested MRSA positive;, all
      of the herds in 5 chains tested MRSA negative and in the remaining 5 chains, MRSA
      positive and MRSA-negative herds were detected. Seven spa types were found, which
      were all previously confirmed to belong to CC398. All of the isolates were
      susceptible to mupirocin, linezolid, rifampicin, fusidic acid and cotrimoxazole.
      Resistance against tetracycline, erythromycin and clindamycin was found in 100,
      74 and 76% of the isolates, respectively. Seventy-nine percent of herds with a
      MRSA-positive supplier of pigs were MRSA positive, whereas 23% of herds with a
      MRSA-negative supplier were MRSA positive (OR=10.8; 95% CI: 1.5-110.1; P=0.011).
      The presence of entirely MRSA-positive and MRSA-negative chains and the strong
      association between the MRSA status of herds and their suppliers illustrates a
      large risk associated with purchasing pigs from MRSA-positive herds; a top-down
      strategy for future control programs is, therefore, a basic requirement. However,
      23% of herds with a MRSA-negative supplier were MRSA positive and furthermore,
      46% of the herds at the top of the pig production chain without a supplier tested
      MRSA positive. This underlined the need for the identification of additional risk
      factors for MRSA.

PMID- 21075467
TI  - Miniaturizing microbial fuel cells.
AB  - Microbial fuel cells (MFCs) represent an emerging technology for electricity
      generation from renewable biomass. Given the demand for a better understanding of
      the bio/inorganic interface that plays a key role in MFC energy production, small
      scale MFCs are receiving considerable attention owing to their intrinsic
      advantages in both fundamental studies and applications as high-throughput
      platforms. Here, we present a brief review centered on the development of
      miniature MFCs at the milliliter to microliter scale. The principles, design
      motifs and experimental demonstrations of representative miniature MFC devices
      and systems are introduced, followed by a discussion of the key challenges and
      opportunities for realizing the exciting potentials of miniaturized MFCs.

PMID- 21075468
TI  - Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with
      radiotherapy in locally advanced pancreatic cancer.
AB  - BACKGROUND AND PURPOSE: To investigate the efficacy and toxicity of a short
      intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with
      celecoxib in locally advanced pancreatic cancer. MATERIAL AND METHODS: The
      Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam
      enrolled 83 eligible patients with unresectable pancreatic cancer in a
      prospective multicentre phase II study. Median age was 62 years, median tumour
      size 40 mm and the majority of the patients (85%) had pancreatic head cancers.
      Treatment consisted of 20*2.5 Gy radiotherapy combined with UFT 300 mg/m(2) per
      day, leucovorin (folinic acid) 30 mg and celecoxib 80 0mg for 28 days concomitant
      with radiotherapy. Four patients were lost to follow-up. RESULTS: Full treatment
      compliance was achieved in 55% of patients, 80% received at least 3 weeks of
      treatment. No partial or complete response was observed. Median survival was 10.6
      months and median time to progression 6.9 months. Toxicity was substantial with
      28% grades III and IV gastro-intestinal toxicity and two early toxic deaths.
      CONCLUSIONS: Based on the lack of response, the substantial toxicity of mainly
      gastro-intestinal origin and the reported mediocre overall and progression free
      survival, we cannot advise our short intensive chemoradiotherapy schedule
      combined with celecoxib as the standard treatment.

PMID- 21075469
TI  - Identification and characterization of integron-associated antibiotic resistant
      Laribacter hongkongensis isolated from aquatic products in China.
AB  - Laribacter hongkongensis is a recently discovered bacterium associated with
      gastroenteritis. In this study, a total of 199 isolates of this species obtained
      from aquatic products (n=462) in Guangzhou City, China, were examined for their
      susceptibility to 19 antimicrobial agents and the presence of antimicrobial
      resistance integrons. The genetic relatedness of the isolates with integrons was
      also evaluated. A PCR-based method was used to screen integrons and found that 13
      (6.5%) of the isolates harbored class 1 integrons. The antimicrobial resistance
      rates of integron-positive isolates were significantly higher than integron
      negative ones for cefepime, ciprofloxacin, gentamicin, tetracycline, trimethoprim
      sulfamethoxazole and rifampicin. Genetic sequence analysis revealed that these
      integrons contained various antimicrobial-resistance genes (dfrA1, dfrA14,
      dfrA17, dfrA32, aadA1, aadA2, aadA5, cmlA5, arr2, ereA and orfC) organized into
      different gene cassettes arrangements including a novel array of dfrA14-arr2
      cmlA5. Pulsed-field gel electrophoresis (PFGE) yielded 13 different patterns
      among 13 integron-positive isolates, which could be grouped into four clusters.
      These indicate the dispersal of multi-resistant integrons among different
      molecular types. To the best of our knowledge, this is the first report showing
      distribution and characterization of class 1 integrons among L. hongkongensis
      isolates.

PMID- 21075470
TI  - Equity in the use of antiretroviral treatment in the public health care system in
      urban South Africa.
AB  - OBJECTIVES: The scaling up of antiretroviral treatment (ART) for HIV-infected
      adults requires a sizeable investment of resources in the South African public
      health care system. It is important that these resources are used productively
      and in ways that reach those in need, irrespective of social status or personal
      characteristics. In this study we evaluate whether the distribution of ART
      services in the public system reflects the distribution of need among adults in
      the urban population. METHODS: Data from a 2008 national survey were used to
      estimate the distribution of socioeconomic status (SES) and sex in HIV-positive
      adults in urban areas. These findings were compared to SES and sex distributions
      in 635 ART users within 6 urban public ART facilities. RESULTS: Close to 40% of
      those with HIV are in the lowest SES quintile, while 67% are women. The
      distributions in users of ART are similar to these distributions in HIV-positive
      people. CONCLUSIONS: Patterns of ART use in study settings correspond to patterns
      of HIV in the urban population at the national level. This suggests that the
      South African ART programme is on track to ensure equitable delivery of treatment
      services in urban settings.

PMID- 21075471
TI  - User-centered requirements engineering in health information systems: a study in
      the hemophilia field.
AB  - The use of sophisticated information and communication technologies (ICTs) in the
      health care domain is a way to improve the quality of services. However, there
      are also hazards associated with the introduction of ICTs in this domain and a
      great number of projects have failed due to the lack of systematic consideration
      of human and other non-technology issues throughout the design or implementation
      process, particularly in the requirements engineering process. This paper
      presents the methodological approach followed in the design process of a web
      based information system (WbIS) for managing the clinical information in
      hemophilia care, which integrates the values and practices of user-centered
      design (UCD) activities into the principles of software engineering, particularly
      in the phase of requirements engineering (RE). This process followed a paradigm
      that combines a grounded theory for data collection with an evolutionary design
      based on constant development and refinement of the generic domain model using
      three well-known methodological approaches: (a) object-oriented system analysis;
      (b) task analysis; and, (c) prototyping, in a triangulation work. This approach
      seems to be a good solution for the requirements engineering process in this
      particular case of the health care domain, since the inherent weaknesses of
      individual methods are reduced, and emergent requirements are easier to elicit.
      Moreover, the requirements triangulation matrix gives the opportunity to look
      across the results of all used methods and decide what requirements are critical
      for the system success.

PMID- 21075472
TI  - Diverging prognostic impacts of hypoxic markers according to NSCLC histology.
AB  - BACKGROUND: We aimed to explore the prognostic impact of the hypoxia induced
      factors (HIFalphas) 1-2 and the metabolic HIF-regulated glucose transporter
      GLUT1, lactate dehydrogenase 5 (LDH5) and carbonic anhydrase IX (CAIX) in non
      small cell lung cancer (NSCLC). METHODS: Tumor and stroma tissue samples from 335
      unselected patients with stage I-IIIA NSCLC were obtained and tissue microarrays
      constructed. Immunohistochemistry was used to evaluate expression. RESULTS: For
      squamous cell carcinoma patients, high tumor cell expression of HIF1alpha and low
      stromal cell expression of HIF1alpha and HIF2alpha correlated significantly with
      a poor disease-specific survival (DSS) in both univariate (tumor HIF1alpha,
      P=0.001; stromal HIF1alpha, P=0.009; stromal HIF2alpha, P=0.005) and multivariate
      analyses (tumor HIF1alpha, HR=3.3, P=0.001; stromal HIF1alpha, HR=2.1, P=0.008;
      stromal HIF2alpha, HR 2.3, P=0.005). Among adenocarcinoma patients high tumor
      expression of GLUT1 and low stromal expression of LDH5 correlated significantly
      with a poor DSS in both univariate (GLUT1, P=0.01; LDH5, P=0.03) and multivariate
      analyses (GLUT1, HR=1.9, P=0.046; LDH5, HR=2.3, P=0.03). CONCLUSION: These
      markers show highly diverging prognostic impacts between histological subgroups
      and between tumor and stromal compartments in NSCLC.

PMID- 21075473
TI  - Define relative incomplete resection by highest mediastinal lymph node metastasis
      for non-small cell lung cancers: rationale based on prognosis analysis.
AB  - PURPOSE: Present research aimed to explore the rationale of defining RIR
      operations by metastatic status of highest nodes. PATIENTS AND METHODS: 549
      surgical patients, bearing pN2-NSCLCs, were enrolled in the current study. R1/R2
      nodes on the right side and L4 nodes on the left were taken as the highest
      mediastinal lymph nodes. The operations were defined "Complete Resection (CR)" if
      the highest nodes were negative. Operations were otherwise "Relative Incomplete
      Resections (RIR)" if the nodes were positive. Exclusion criteria included:
      metastatic carcinomas or small cell lung cancer, prior history of induction
      therapy, exploratory thoracotomy, palliative resection, and massive pleural
      dissemination, as well as cases without "highest" mediastinal nodal pathology.
      The survival rate was calculated using the life-table and Kaplan-Meier method.
      Comparisons between groups were calculated using the Log-rank test. RESULTS: A
      total of 6865 lymph nodes (5705 mediastinal and 1160 regional, average 12.6+/-6.4
      nodes for each patient) were removed. Total cases included 246 RIR (100 left and
      146 right side) and 303 CR (108 left and 195 right). The overall 5-year survival
      rate was 22% and the median survival time was 28.29 months. Five-year survival
      rates of the CR and RIR group were statistically significant (29% and 13%,
      respectively p<0.0001). L4 and R1/R2 lymph nodes had similar position for
      defining RIR; no obvious survival difference was indicated between either side
      (p=0.464 in CR groups, p=0.647 in RIR groups). N2 subcategories and skip
      metastasis were closely associated with highest nodal involvement (p<0.0001).
      Multivariate analysis showed CR/RIR assignment, tumor size, N2 disease
      stratification, pathological T status, and number of positive mediastinal nodes
      were risk factors for 5-year survival in the present case series. CONCLUSION:
      Involvement of the highest mediastinal lymph nodes is highly predictive of poor
      prognosis and indicates an advanced stage of the disease. Therefore, it may be
      appropriate to assign R1/R2 or L4 as criterion for defining RIR or CR cases in
      surgical NSCLC cases.

PMID- 21075474
TI  - Klotho is a novel biomarker for good survival in resected large cell
      neuroendocrine carcinoma of the lung.
AB  - BACKGROUND: In terms of prognosis, large cell neuroendocrine carcinoma (LCNEC)
      differs distinctively from other non-small cell lung cancers, with the prognosis
      of LCNEC being poor, even for early-stage disease. Improvements in survival
      require a biomarker capable of defining a subset of patients destined to do
      poorly so that these patients can be targeted for additional therapies, including
      chemotherapy. In this study, we focused on the Klotho gene, which is an anti
      aging gene known to be a potential tumor suppressor. We investigated whether the
      immunohistochemical expression of Klotho can predict survival patients with
      resected LCNEC. METHODS: The histological characteristics of patients receiving
      an initial diagnosis of LCNEC (n=30) at Tokyo Medical University Hospital were
      retrospectively reviewed, and multiple variables including stage,
      lymphangioinvasion, lymph node status and the expression of Klotho as identified
      using an immunohistochemical analysis, were assessed. RESULTS: Immunostaining for
      Klotho was mostly cytoplasmic, and Klotho expression was seen in 10 patients
      (33.3%) but not in 20 patients (66.7%). The expression of Klotho was
      significantly associated with a good outcome of resected patients with LCNEC and
      Klotho(-) was associated with increased LCNEC risk by multivariate analysis
      (hazard ratio 4.92, 95% confidence interval 1.04-23.24, p=0.044). Neither lymph
      node status nor lymphangioinvasion were significantly associated with a poor
      survival. However, among patients without lymph node metastasis or angioinvasion,
      the survival benefit of Klotho expression in the primary tumor was significantly
      higher, compared with that of patients without Klotho expression. CONCLUSION:
      Klotho staining provides a new biomarker for a good outcome in patients with
      LCNEC, especially among patients without lymph node metastasis or
      lymphangioinvasion.

PMID- 21075475
TI  - Sojourn time and lead time projection in lung cancer screening.
AB  - OBJECTIVES: We investigate screening sensitivity, transition probability and
      sojourn time in lung cancer screening for male heavy smokers using the Mayo Lung
      Project data. We also estimate the lead time distribution, its property, and the
      projected effect of taking regular chest X-rays for lung cancer detection.
      METHODS: We apply the statistical method developed by Wu et al. [1] using the
      Mayo Lung Project (MLP) data, to make Bayesian inference for the screening test
      sensitivity, the age-dependent transition probability from disease-free to
      preclinical state, and the sojourn time distribution, for male heavy smokers in a
      periodic screening program. We then apply the statistical method developed by Wu
      et al. [2] using the Bayesian posterior samples from the MLP data to make
      inference for the lead time, the time of diagnosis advanced by screening for male
      heavy smokers. The lead time is distributed as a mixture of a point mass at zero
      and a piecewise continuous distribution, which corresponds to the probability of
      no-early-detection, and the probability distribution of the early diagnosis time.
      We present estimates of these two measures for male heavy smokers by simulations.
      RESULTS: The posterior sensitivity is almost symmetric, with posterior mean 0.89,
      and posterior median 0.91; the 95% highest posterior density (HPD) interval is
      (0.72, 0.98). The posterior mean sojourn time is 2.24 years, with a posterior
      median of 2.20 years for male heavy smokers. The 95% HPD interval for the mean
      sojourn time is (1.57, 3.35) years. The age-dependent transition probability is
      not a monotone function of age; it has a single maximum at age 68. The mean lead
      time increases as the screening time interval decreases. The standard error of
      the lead time also increases as the screening time interval decreases.
      CONCLUSION: Although the mean sojourn time for male heavy smokers is longer than
      expected, the predictive estimation of the lead time is much shorter. This may
      provide policy makers important information on the effectiveness of the chest X
      rays and sputum cytology in lung cancer early detection.

PMID- 21075476
TI  - No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical
      outcomes of platinum-based chemotherapies in non-small cell lung cancer: a meta
      analysis.
AB  - BACKGROUND: The nucleotide excision repair (NER) pathway modulates platinum-based
      chemotherapeutic efficacy by removing drug-induced DNA damage. METHODS: To
      summarize published data on the association between NER genes and responses to
      platinum-based chemotherapies in non-small cell lung cancer (NSCLC), we performed
      a meta-analysis of 17 published studies of ERCC1 C118T/C8092A and ERCC2
      Lys751Gln/Asp312Asn polymorphisms, including 2097 cancer patients. Primary
      outcomes included objective response (TR) (i.e., complete response+partial
      response vs. stable disease+progressive disease), progression-free survival (PFS)
      and overall survival (OS). We calculated odds ratio (OR) or hazard ratio (HR)
      with 95% confidence interval (CI) to estimate the risk or hazard. RESULTS: We
      found that none of the ERCC1 C118T/C8092A and ERCC2 Lys751Gln/Asp312Asn
      polymorphisms alone was statistically significantly associated with objective
      response, PFS and OS in NSCLC patients. CONCLUSION: There is no evidence to
      support the use of NER ERCC1 C118T/C8092A and ERCC2 Lys751Gln/Asp312Asn
      polymorphisms as prognostic predictors of platinum-based chemotherapies in NSCLC.

PMID- 21075477
TI  - Evaluation of 39 cases of pediatric cutaneous head and neck melanoma.
AB  - BACKGROUND: Studies examining head and neck (H&N) melanoma in the pediatric
      population are scarce. OBJECTIVE: The goal of this study is to describe pediatric
      H&N melanoma with the intent of increasing understanding of the course of
      disease. METHODS: The Duke Melanoma Database and Duke Tumor Registry Database
      were searched for patients with a diagnosis of melanoma occurring on the H&N
      before age 18 years, with exclusion of ocular/mucosal/aerodigestive melanomas.
      RESULTS: Queries yielded 39 Caucasian pediatric patients, 24 (61.5%) of them
      male. The mean age at diagnosis was 14.2 years (15 years, median). The primary
      sites were represented as follows: cutaneous auricular (1/39, 2.6%), facial
      (15/39, 38.5%), and scalp/neck (23/39, 59%). The follow-up time ranged from 2
      months to 23 years with a median of 9.9 years (95% confidence interval: 6.2-13
      years). At the time of follow-up, there were 12 (12/39, 30.8%) melanoma
      associated deaths. The anatomic distribution of primary melanoma for these 12
      patients follows: 4 (33.3%) facial and 8 (66.7%) scalp/neck. Histologic data
      revealed 24 (61.5%) tumors classified as superficial spreading melanoma with
      nodular melanoma (12.8%) a distant second. The mean Breslow depth for patients
      with melanoma-related mortality was 2.4 mm, compared with 1.8 mm for those who
      were alive at last follow-up. LIMITATIONS: Small sample size limited this study.
      CONCLUSION: This study found that the majority (59%) of H&N melanomas presented
      as scalp or neck lesions with a predilection for adolescents and boys. Those who
      experienced melanoma-related mortality had thicker lesions. Superficial spreading
      melanoma was the most common subtype.

PMID- 21075478
TI  - Central hair loss in African American women: incidence and potential risk
      factors.
AB  - BACKGROUND: Although central scalp hair loss is a common problem in African
      American women, data on etiology or incidence are limited. OBJECTIVE: We sought
      to determine the frequency of various patterns and degree of central scalp hair
      loss in African American women and to correlate this with information on hair
      care practices, family history of hair loss, and medical history. METHODS: Five
      hundred twenty-nine subjects at six different workshops held at four different
      sites in the central and/or southeast United States participated in this study.
      The subjects' patterns and degree of central scalp hair loss were independently
      assessed by both subject and investigator using a standardized photographic
      scale. Subjects also completed a detailed questionnaire and had standardized
      photographs taken. Statistical analysis was performed evaluating answers to the
      questionnaire relative to pattern of central hair loss. RESULTS: Extensive
      central scalp hair loss was seen in 5.6% of subjects. There was no obvious
      association of extensive hair loss with relaxer or hot comb use, history of
      seborrheic dermatitis or reaction to a hair care product, bacterial infection, or
      male pattern hair loss in fathers of subjects; however, there was an association
      with a history of tinea capitis. LIMITATIONS: There was no scalp biopsy
      correlation with clinical pattern of hair loss and further information on
      specifics of hair care practices is needed. CONCLUSIONS: This central scalp
      photographic scale and questionnaire provide a valid template by which to further
      explore potential etiologic factors and relationships to central scalp hair loss
      in African American women.

PMID- 21075479
TI  - The effects of pajama fabrics' water absorption properties on the stratum corneum
      under mildly cold conditions.
AB  - BACKGROUND: The interaction of textiles with the skin is a fertile area for
      research. OBJECTIVE: The aim of this study was to investigate the effects of
      clothing fabric on the stratum corneum (SC) under mildly cold conditions.
      METHODS: A longitudinal controlled parallel study was designed to investigate the
      effects of the liquid/moisture absorption properties of pajama fabrics on the SC
      water content, transepidermal water loss, skin surface acidity (pH), and sebum.
      RESULTS: The hygroscopicity of pajama fabrics had significant associations with
      the SC water content and transepidermal water loss on the skin of the volunteers'
      backs. Sebum in the hydrophilic cotton group was slightly lower than in the
      polyester groups and hydrophobic cotton groups. Subjects felt warmer in the
      hydrophobic groups than in the hydrophilic groups. The hydrophilicity of the
      fabric also showed an association with overnight urinary free catecholamines.
      LIMITATIONS: In this study, detailed components of sebum were not analyzed.
      CONCLUSIONS: The hygroscopicity of the fabric may be a key factor influencing SC
      hydration during daily wear under mildly cold conditions.

PMID- 21075481
TI  - [Severe aortic stenosis in the elderly: bad prognosis means that surgery is
      necessary?].

PMID- 21075480
TI  - Ventral striatal volume is associated with cognitive decline in older people: a
      population based MR-study.
AB  - Striatal degeneration may contribute to cognitive impairment in older people.
      Here, we examine the relation of degeneration of the striatum and substructures
      to cognitive decline and dementia in subjects with a wide range of cognitive
      function. Data are from the prospective community-based Honolulu Asia Aging Study
      of Japanese American men born 1900-1919. Brain magnetic resonance imaging (MRI)
      (1.5 T) was acquired on a stratified subsample (n = 477) that included four
      groups defined by cognitive status relative to the scan date: subjects without
      dementia (n = 347), subjects identified as demented 2-3 years before brain
      scanning (n = 30), at the time of scanning (n = 58), and 3-5 years after scanning
      (n = 42). Volumes of the striatum, including the accumbens, putamen, and caudate
      nucleus were automatically estimated from T1 MR images. Global cognitive function
      was measured with the cognitive ability screening instrument (CASI), at four
      examinations spanning an 8-year interval. Trajectories of cognitive decline were
      estimated for each quartile of striatal volume using mixed models, controlling
      for demographic variables, measures of cerebro-vascular damage, global brain
      atrophy, and hippocampal volume. Diagnosis of dementia before, during, and after
      brain scanning was associated with smaller volumes of n. accumbens and putamen,
      but not with caudate nucleus volume. Subjects in the lowest quartile of n.
      accumbens volume, both in the total sample and in the subjects not diagnosed with
      dementia during the study, had a significantly (p < 0.0001) steeper decline in
      cognitive performance compared with those in the highest quartile. In conclusion,
      volumes of the n. accumbens and putamen are closely associated with the
      occurrence of dementia and n. accumbens volume predicts cognitive decline in
      older people. These associations were found independent of the magnitude of other
      pivotal markers of cognitive decline, i.e. cerebro-vascular damage and
      hippocampal volume. The present study suggests a role for the ventral striatum in
      the development of clinical dementia.

PMID- 21075482
TI  - [Geriatric assessment of patients over 75 years-old admitted to an emergency
      department observation unit].

PMID- 21075484
TI  - [Sexual dysfunction in the elderly. Pathophysiological and medical issues.
      Treatment of erectile dysfunction].
AB  - Erectile dysfunction (ED) is a very distressing condition that not only
      negatively affects the elderly man's sexual ability, but also his overall quality
      of life and that of his partner. Encouraging men, alone or as a couple, to seek
      professional help is a major educational challenge which needs to be met by
      medical, social and political initiatives. The exact pathogenesis of ED remains
      unknown, but is presumed to be multifactorial; vascular disease is the most
      frequent cause with endothelial dysfunction being the common denominator. It has
      been postulated that ED is a sentinel symptom of cardiovascular clinical events
      and should prompt investigation and intervention for cardiovascular risk factors.
      Therefore, when a patient presents with ED, a thorough history and physical
      examination should be performed, as well as appropriate laboratory tests aimed at
      detecting associated diseases.

PMID- 21075485
TI  - [Renal biopsy in patients aged 65 years or older: are there differences in the
      indication and histopathology compared to other patients?].
AB  - BACKGROUND: Renal biopsy (RB) represents the gold standard for diagnosis of
      kidney diseases. In this paper we analyse whether the indication of RB and
      histopathology in patients 65 years or older is different from the other
      patients. MATERIAL AND METHODS: Retrospective study of 93 native renal biopsies
      performed in the General Hospital of Segovia in the period 2004-2008. The RB was
      performed percutaneously under ultrasound guidance in real time, using a 16G
      automatic needle. RESULTS: Mean age of biopsied patients was 56.89 +/- 19 (range
      14-89) , and 57% were males. A total of 39RB were performed on people aged 65
      years or older. Overall, nephrotic syndrome (NS) is the most common indication of
      RB, and IgA glomerulonephritis the most common histology. In people >= 65 years,
      acute renal failure (ARF) is the most common indication for RB, and rapidly
      progressing (crescentic) glomerulonephritis/vasculitis the most detected the
      diagnosis. When taking age into account, no significant differences in the number
      of glomeruli obtained by RB or in the number of RB performed on the same patient.
      CONCLUSIONS: In people 65 years or older, ARF is the main indication of RB and
      crescentic glomerulonephritis/vasculitis the most frequent diagnosis.

PMID- 21075486
TI  - [Psychological functioning and aging. Learning from longitudinal studies].
AB  - Population-based longitudinal studies are very useful tools for investigating the
      characteristics of the aging process among different geographical and socio
      cultural contexts. On the other hand, these kind of projects look at a wide range
      of key issues of aging. In this review, most recent psychological findings in
      this field are analysed. The increasing interest in longitudinal studies for
      psychological variables is shown, as well as explicit links with other areas of
      study. Finally, main areas of improvement are identified according to future
      analysis of psychological variables, regarding both conceptual and methodological
      issues.

PMID- 21075487
TI  - [Research into health care models in geriatrics: proposals for the future].

PMID- 21075488
TI  - [Outcomes of elderly patients admitted to hospital due to severe aortic stenosis
      and rejected for surgical intervention].
AB  - INTRODUCTION: The natural outcome of untreated severe symptomatic aortic stenosis
      in the elderly patient is extremely poor. In this analysis we studied the
      clinical, ultrasound and analytical variables, that could be associated with the
      vital prognosis in this patient sub-group. MATERIAL AND METHODS: A retrospective
      study of patients admitted to our hospital between 2004 and 2008 due to symptoms
      associated with the presence of a severe aortic stenosis and were not considered
      for surgery. Demographic, concomitant diseases, ultrasound (ejection fraction,
      transvalvular gradient, valve area) and laboratory analytical data (haemoglobin,
      creatinine, atrial natriuretic peptide) were analysed and the logistic euroscore
      was calculated. RESULTS: A total of 49 patients were included (73.5% women), with
      a mean age of 82.2+/-5.5 years. The median follow up was 396.0 days,
      interquartile range 99.5-731.0 days, with a mortality of 75.5%. In the
      multivariate analysis, only the left ventricular ejection fraction measured by
      ultrasound was an important predictor as regards life expectancy (EF 35-50%: HR
      3.74, IC 95% CI; 1.11-12.65, P=0.034; EF<35%: HR 6.76, IC 95% CI; 1.86-24.52,
      p=0.004). CONCLUSION: The life expectancy of elderly patients with untreated
      severe symptomatic aortic stenosis is very limited, with a high mortality during
      the first year. The ejection fraction is significantly associated with the
      prognosis in these patients.

PMID- 21075489
TI  - [Functional level and quality of life in ankylosing spondylitis, pilot study
      after 16 weeks TNF blocker treatment].
AB  - BACKGROUND AND OBJECTIVES: The aim of the present study is to assess the impact
      of infliximab and etanercept, TNF-alpha (tumour necrosis factor-alpha blockers)
      on functional disability and quality of life in thirteen patients over 65 years
      old with ankylosing spondylitis (AS). PATIENTS AND METHODS: We consecutively
      included patients over 65 years-old, attending our clinic from Rheumatology
      Service in Hospital Clinico de Granada. These patients were all refractory to
      conventional therapy with disease-modifying anti-rheumatic drugs (DMARD). Disease
      activity was assessed using BASDAI index (bath ankylosing spondylitis disease
      activity index). Functional disability was assessed using BASFI (bath ankylosing
      spondylitis functional index) and ASQol index (ankylosing spondylitis quality of
      life index). RESULTS: We present a pilot study with 13 patients over 65 years-old
      treated with TNF blockers for 16 weeks. A significant decrease in disease
      activity was observed. Mean values of VAS (visual analogue scale) pain scores and
      disease decreases significantly after treatment (from 6.72 to 3.67 and 6.15 to
      2.79 respectively), less than 4, which is considered an acceptable BASDAI
      response. Functional ability (BASFI) and health related quality of life (HRQOL)
      improved significantly from 6.15 to 2.79 and 13.85 to 4.22. CONCLUSIONS: Our
      results are consistent with the data available in the literature about TNF
      blockers decreasing clinical signs of the disease. Disease activity had
      significantly decreased 16 weeks after the onset of TNF blocker therapy.
      Functionality and quality of life have been also improved in elderly people with
      AS.

PMID- 21075490
TI  - Welfare state, labour market inequalities and health. In a global context: an
      integrated framework. SESPAS report 2010.
AB  - Since the nineteen seventies, high- and low-income countries have undergone a
      pattern of transnational economic and cultural integration known as
      globalization. The weight of the available evidence suggests that the effects of
      globalization on labor markets have increased economic inequality and various
      forms of economic insecurity that negatively affect workers' health. Research on
      the relation between labor markets and health is hampered by the social
      invisibility of many of these health inequalities. Empirical evidence of the
      impact of employment relations on health inequalities is scarce for low-income
      countries, small firms, rural settings, and sectors of the economy in which
      "informality" is widespread. Information is also scarce on the effectiveness of
      labor market interventions in reducing health inequalities. This pattern is
      likely to continue in the future unless governments adopt active labor market
      policies. Such policies include creating jobs through state intervention,
      regulating the labor market to protect employment, supporting unions, and
      ensuring occupational safety and health standards.

PMID- 21075491
TI  - [Health in all policies, a challenge for public health in Spain. SESPAS report
      2010].
AB  - The objective of SESPAS Report 2010 is to enhance the incorporation of the
      principle of Health in all Policies in public health in Spain. The fundamental
      principle behind this slogan is very simple: Health is strongly influenced by the
      environment, how we live, work, eat, walk or enjoy our leisure time. Moreover,
      these living conditions depend not only on individual decisions but are
      determined by social, cultural, economic or environmental factor. Consequently,
      policy decisions that influence the health of people not just those related to
      services or health policy, but primarily those taken in other public, private,
      political and civic contexts. SESPAS Report 2010 has four parts. It begins with
      and introductory chapter on the challenges of incorporating the principle of
      Health in all Policies in public health. The second part consists of several
      articles of reflection on the relationship between the health care system and
      public health. The third part focuses on cross-sectoral public health policies.
      The report ends with several articles on cross-cutting issues such as public
      health education, information, research, evaluation and ethics in public health
      policies.

PMID- 21075492
TI  - [Social inequalities in child health. SESPAS report 2010].
AB  - There is considerable evidence of the impact of poverty and social exclusion on
      child health. In the last few years, interest has grown in the concept of social
      gradients in health, according to social position, family educational level,
      gender, and ethnic background. Several cohort studies have demonstrated an
      association between maternal socioeconomic position during the prenatal period
      and adult health. The Commission on Social Determinants of Health of the World
      Health Organization proposed closing the health gap in a generation by giving a
      major role to early child development. Family educational level and academic
      achievement are fundamental determinants of health inequalities. There is scarce
      empirical evidence on the effectiveness of interventions to reduce child health
      inequalities. Most of the interventions in children and adolescents aim to change
      individual behavior, and very few have been critically evaluated. The present
      manuscript provides a review of initiatives and recent interventions aimed at
      reducing social inequalities, as well as a checklist to be taken into account in
      interventions on health promotion and disease prevention in schools from the
      perspective of social and gender inequalities. Strategies for data collection,
      research and health and educational policies are proposed.

PMID- 21075493
TI  - [On the training of public health professionals, some advances and many
      challenges. SESPAS Report 2010].
AB  - Given the progressive institutionalization of public health in Spain, as shown by
      the recently approved Valencian and Catalan public health laws and the national
      draft, reflection on the training of the public health professionals who will
      apply these rules is essential. Becoming a public health professional requires a
      certain degree of competence in developing activities to promote and protect
      citizens' health, mainly that of the population at large. The acquisition of
      these competencies continues throughout professional life, beginning with a
      masters' degree in public health until advanced expertise is achieved,
      characterized by the capacity innovate, lead and provoke changes in public
      health, both nationally and internationally. Some of the challenges proposed
      include developing research on public health training, producing a strategic plan
      for public health training, and establishing an accreditation system, initially
      voluntary, promoted by professional societies.

PMID- 21075494
TI  - Implementing high-fidelity simulation in Canada: reflections on 3 years of
      practice.
AB  - This paper explores our experiences in implementing and using high-fidelity
      simulation (HFS) over the last three years, in the context of the results of the
      Canadian Association of Schools of Nursing (CASN) health 2006 simulation survey,
      which explored the use of simulation across Canada in professional health
      education. Considerations for the practical implementation of simulation based on
      evaluations at the University of British Columbia School of Nursing are
      discussed. The rapid increase in the uptake of simulation-based education in
      Canada is due in large part to the belief that these techniques offer a safe
      environment for learners to improve competence. Students and teachers have
      identified positive learning experiences with high-fidelity simulation,
      particularly with respect to complex patient care scenarios, multidisciplinary
      team scenarios, student team work (i.e., team-based learning), and reflective
      debriefing. Despite these benefits there have been significant resource
      implications from adopting these technologies. The use of team-based learning and
      reflective debriefing appeared to be a focal area for emphasis in the planning of
      clinical simulation experiences. A team focused learning approach may also offer
      a more cost-efficient strategy for clinical simulation.

PMID- 21075495
TI  - Employment relations, social class and health: a review and analysis of
      conceptual and measurement alternatives.
AB  - Employment relations, as a theoretical framework for social class, represent a
      complementary approach to social stratification. Employment relations introduce
      social relations of ownership and control over productive assets to the analysis
      of inequalities in economic (e.g., income), power (occupational hierarchy), and
      cultural (e.g., education) resources. The objectives of this paper are to briefly
      clarify the theoretical background on socio-economic indicators used in social
      epidemiology and to conduct a review of empirical studies that adopt relational
      social class indicators in the socio-epidemiological literature. Measures of
      employment relations in social determinants of health research can be classified
      within two major conceptual frameworks: 1) "Neo-Weberian", like the National
      Statistics Socio-Economic Classification (NS-SEC) which is widely used in the
      United Kingdom; and 2) "Neo-Marxian", like Erik O. Wright's social class
      indicators, which are being used by social epidemiologists in the Americas and
      Europe. Our review of empirical findings (49 articles found) reveals that the
      relation between employment relations and health does not necessarily imply a
      graded relationship. For example, small employers can exhibit worse health than
      highly skilled workers, and supervisors can display worse health than frontline
      workers. The policy implications of employment relations research are therefore
      different, and complement those of income or education health gradient studies.
      While the latter studies tend to emphasize income redistribution policy options,
      employment relations implicate other factors such as workplace democracy and
      social protection. Our analysis confirms that the current transformation of
      employment relations calls for new social class concepts and measures to explain
      social inequalities in health and to generate policies to reduce them.

PMID- 21075496
TI  - Better dead than dishonored: masculinity and male suicidal behavior in
      contemporary Ghana.
AB  - In Ghana reliable official data on suicidal behavior are not available. There is
      also limited empirical research on suicidal behavior in the country. At the same
      time, police-recorded suicide data, media reports, and communication from
      professionals in the field indicate that suicidal behavior is a growing problem.
      To identify current patterns and meanings of male suicidal behavior in Ghana, the
      study examined official police data spanning 2006-2008. This investigation
      revealed that reported cases of fatal and nonfatal suicidal behavior
      overwhelmingly involved males. Furthermore, the majority of males who engaged in
      suicidal acts did so to deal with feelings of shame and dishonor of variable
      sources. Findings suggest changing the rigid dichotomization associated with male
      female gender roles and socialization that emphasize masculinity ideals in Ghana
      and the need for increased research and the promotion of counseling for males
      facing emotional stress.

PMID- 21075497
TI  - Professional projects and institutional change in healthcare: the case of
      American dentistry.
AB  - This paper combines resources from the organization studies and sociology
      literatures to advance understanding of institutional change processes in
      healthcare that emerge from the professionalization projects of occupations.
      Conceptually, we introduce a model that combines the 'archetype' approach to
      analyzing structural change with a framework for analyzing the agency of emergent
      professions. We then employ the model to frame a historical case analysis (1972
      2009) of the highly contested process by which the occupation of dental hygiene
      in the US fought to introduce a new organizational form, the alternative practice
      hygiene (APH) archetype. This archetype challenges the traditional model (the
      dentist's office archetype) that is supported by the dominant dentistry
      profession. Our analysis contributes two main sets of empirical findings. First,
      we present a systematic comparison of the APH and Dentist's Office archetypes in
      terms of their belief systems, formal structures, agents, and policy implications
      (e.g., access to services). Second, we provide an account of the agency of dental
      hygienists' attempts to secure the APH model as part of their professionalization
      project.

PMID- 21075498
TI  - Two-year survival and neurodevelopmental outcomes after cardiopulmonary
      resuscitation in neonatal patients after complex cardiac surgery.
AB  - AIM: To examine survival and neurodevelopmental outcomes in neonates having post
      operative cardiopulmonary resuscitation (CPR). METHODS: This inception cohort
      study included all neonates (6 weeks old or less) who received postoperative CPR
      (Group 1) after cardiac surgery from 1996 to 2005, matched for heart defect, year
      of surgery, chromosomal abnormality, and socioeconomic status to two neonates who
      did not receive postoperative CPR (Group 2). Two-year neurodevelopment was
      prospectively assessed with Bayley Scales of Infant Development II and Adaptive
      Behavior Assessment System II. Pre-, intra-, and post-operative variables were
      collected prospectively. Cardiac arrest variables were collected retrospectively.
      Predictors of mortality were analyzed by univariate analysis and conditional
      multiple logistic regression. RESULTS: There were 29 patients in Group 1, and 58
      patients in Group 2. In survivors, there were no significant differences between
      Groups 1 and 2 in outcomes [mean (SD)] of mental developmental index [84.5 (12.2)
      vs. 81.0 (18.9)], psychomotor developmental index [82.8 (13.8) vs. 80.1 (21.9)],
      General Adaptive Composite [84.6 (15.3) vs. 84.3 (19.2)], Motor scale [8.4 (3.2)
      vs. 8.0 (3.8)], or delay on any of these scales. Two-year mortality [58.6% Group
      1; 8.6% Group 2], was associated on conditional multiple logistic regression with
      CPR (OR 26.6; 95% CI, 5.4, 129.5). In Group 1, on multiple logistic regression, 2
      year mortality was associated with minutes of chest compressions (OR 1.04, 95%
      CI, 1.01, 1.08). CONCLUSIONS: Among neonates having cardiac surgery, CPR is
      associated with greater mortality. There is no evidence that CPR survivors have
      different 2-year neurodevelopmental outcomes than those neonates not having CPR.

PMID- 21075499
TI  - Basic life support providers' assessment of centre of the chest and inter-nipple
      line for hand position and their underlying anatomical structures.
AB  - INTRODUCTION: Effective chest compression is an integral part of good quality
      cardiopulmonary resuscitation. There remains uncertainty over the optimal method
      for identifying the correct hand position for chest compression. The aim of this
      study was to identify the relationship between basic life support (BLS) providers
      assessment of the inter-nipple line (INL) versus the centre of the chest (CoC)
      and to identify the anatomical structures underneath these landmarks. METHOD:
      Thirty consecutive patients having elective CT scans of the thorax were recruited
      and photographs of the patient fully clothed were taken in the supine position.
      30 healthcare students trained in BLS were asked to mark the 'point between the
      nipples' and the 'centre of the chest' on each photograph in a random sequence.
      Corresponding points were marked on the CT images and the underlying anatomical
      structures were identified. RESULTS: Hand positions using CoC landmark were
      significantly higher and were more variable than INL landmark (measurement
      represented as ratio of sternal length: mean CoC 0.709, 95% CI 0.677, 0.740
      versus mean INL 0.803 95% CI 0.772, 0.835; p<0.0001). Structures underneath CoC
      and INL hand positions were significantly different; CoC compressing
      predominantly the aortic arch and ascending aorta and INL compressing the left
      ventricle and left ventricular outflow (p<0.001). Hand positions were not
      significantly affected by gender of patients. CONCLUSION: Both the centre of the
      chest landmark and inter-nipple line identify positions on the lower third of the
      sternum. The centre of the chest technique identifies a point that is
      consistently higher and more variable than the inter-nipple line. Structures
      compressed under both landmarks were different although the implications of this
      are unknown.

PMID- 21075501
TI  - The value of serological markers in the diagnosis and prognosis of endometriosis:
      a prospective case-control study.
AB  - OBJECTIVE: We analyzed selected well-known and less well-known serum markers that
      have been proposed for diagnosis and severity assessment of endometriosis, in a
      case-control study. STUDY DESIGN: This prospective study was carried out in a
      Clinical Department of Gynecology in Iasi, Romania. Study participants included
      endometriosis patients, and controls in whom laparoscopy had excluded
      endometriosis. Each case and control was investigated for serum levels of CA125,
      TNF, IL-1, IL-6 and IL-8. The data were correlated with clinical symptoms and
      revised American Fertility Society (rAFS) score and stage, and interpreted by
      Mann-Whitney U-test and ANOVA regression analysis. RESULTS: Over the course of 1
      year, 24 cases of endometriosis and 24 controls of matched age were selected. The
      rAFS stages were: stage I, 12.5%; stage II, 16.7%; stage III, 58.3%; and stage
      IV, 12.5%. CA125 levels were over the cut-off of 35 IU/l in 54% of patients
      (versus 8% of controls), averaging 67.5 (CI95: +/-17.5). The sensitivity and
      specificity were 54% and 91%, respectively, with a p value of <0.001
      (statistically significant). For IL-6, 71% of cases and 87% of controls were
      above the cut-off of 2 pg/ml, with an average of 11.83 +/- 7. The sensitivity and
      specificity were 71% and 12%, respectively, but the difference was not
      statistically significant, p = 0.071. Other tested serum markers had no
      discrimination value. A correlation with severity of endometriosis was seen for
      CA125 (p = 0.03) but not for IL-6, by ANOVA. CONCLUSION: CA125 correlated with
      endometriosis screening and severity, indicating its superiority as a marker for
      further, larger studies.

PMID- 21075502
TI  - "Cold spots" in protein cold adaptation: Insights from normalized atomic
      displacement parameters (B'-factors).
AB  - Many analyses published in the last decade suggest that enzymes isolated from
      cold-adapted organisms are characterized by a higher flexibility of their
      molecular structure. Recently, it has been argued that all cold-adapted enzymes
      with catalytic efficiency greater than that of their mesophilic counterparts
      display local flexibility or rigidity that are likely to cooperate, each acting
      on specific areas of the enzyme structure. Here we report an analysis of the
      normalized thermal B-factor distributions in psychrophilic proteins compared with
      those of their mesophilic and thermophilic counterparts with the aim to detect
      statistically significant local variations of relative backbone flexibility
      possibly linked to cold adaptation. We utilized a strategy based mainly on intra
      family comparison of local distribution of normalized B-factors. After careful
      statistical treatment of data, the picture emerging from our results suggests
      that the distribution of the flexibility in psychrophilic enzymes is locally more
      heterogeneous than in their respective mesophilic homologues.

PMID- 21075503
TI  - Preparation of novel activated carbons from H2SO4-pretreated corncob hulls with
      KOH activation for quick adsorption of dye and 4-chlorophenol.
AB  - Corncob hull was immersed in 25 wt% H(2)SO(4) and was carbonized in an oven at
      290  degrees C for 2h to obtain the char. The char was then activated for 1h at
      780  degrees C by KOH at weight ratio of KOH/char of 2.5, 3.0, and 3.5. SEM
      photos of the carbons revealed that the cell wall of corncob hull was etched into
      thin film structure. It was shown that the adsorption isotherms of methylene blue
      and 4-chlorophenol on the carbons were well fitted by the Langmuir equation.
      Moreover, the adsorption kinetics could be satisfactorily described by the
      Elovich equation. The normalized standard deviations are less than 2.8%. The high
      fraction of adsorption amount adsorbed within 1 min to that at saturation
      demonstrated the advantage of the prepared activated carbons. The fraction of
      adsorption amount within 1 min to that at saturation (q(1)/q(mon)) for the
      adsorption of 4-CP is high up to 0.807. Such quick adsorption behavior was mainly
      attributed to the presence of the thin film structure of carbons.

PMID- 21075504
TI  - Influence of pine or oak wood on the degradation of alachlor and metalaxyl in
      soil.
AB  - The objective of this work was to study the influence pine or oak wood added to
      soil as an amendment (5% w/w) had on the degradation rate of two pesticides,
      alachlor and metalaxyl, with different hydrophobic character. The formation of
      pesticide metabolites and the soil dehydrogenase activity in non-amended and
      amended soil samples were also monitored. The degradation of metalaxyl followed
      first-order kinetics, while the degradation of alachlor followed first-order or
      biphasic kinetics in the soil samples studied. The results indicated that the
      degradation rate was slower for metalaxyl than for alachlor, and for both
      pesticides followed the order: pine amended soil < oak amended soil < non-amended
      soil. The faster degradation rate in non-amended soil was attributed to the
      higher sorption of pesticides by wood amended soils. The alachlor ethane sulfonic
      acid (ESA), and two metalaxyl metabolites (2-[(2,6-dimethylphenyl)
      methoxyacetylamino]-propionic acid and N-(2,6-dimethylphenyl)-2-methoxy
      acetamide) were detected during the incubation period. Soil dehydrogenase
      activity recorded close values in non-amended and amended soil treated with
      alachlor, but it was higher in wood amended soil treated with metalaxyl. Pine and
      oak wood increase the immobilization of the pesticides studied, but they also
      limit their bioavailability in soil by decreasing their degradation rate in
      amended soil.

PMID- 21075505
TI  - Adaptive management of natural resources--framework and issues.
AB  - Adaptive management, an approach for simultaneously managing and learning about
      natural resources, has been around for several decades. Interest in adaptive
      decision making has grown steadily over that time, and by now many in natural
      resources conservation claim that adaptive management is the approach they use in
      meeting their resource management responsibilities. Yet there remains
      considerable ambiguity about what adaptive management actually is, and how it is
      to be implemented by practitioners. The objective of this paper is to present a
      framework and conditions for adaptive decision making, and discuss some important
      challenges in its application. Adaptive management is described as a two-phase
      process of deliberative and iterative phases, which are implemented sequentially
      over the timeframe of an application. Key elements, processes, and issues in
      adaptive decision making are highlighted in terms of this framework. Special
      emphasis is given to the question of geographic scale, the difficulties presented
      by non-stationarity, and organizational challenges in implementing adaptive
      management.

PMID- 21075506
TI  - Assessing the environmental performance of English arable and livestock holdings
      using data from the Farm Accountancy Data Network (FADN).
AB  - Agri-environment schemes (AESs) have been implemented across EU member states in
      an attempt to reconcile agricultural production methods with protection of the
      environment and maintenance of the countryside. To determine the extent to which
      such policy objectives are being fulfilled, participating countries are obliged
      to monitor and evaluate the environmental, agricultural and socio-economic
      impacts of their AESs. However, few evaluations measure precise environmental
      outcomes and critically, there are no agreed methodologies to evaluate the
      benefits of particular agri-environmental measures, or to track the environmental
      consequences of changing agricultural practices. In response to these issues, the
      Agri-Environmental Footprint project developed a common methodology for assessing
      the environmental impact of European AES. The Agri-Environmental Footprint Index
      (AFI) is a farm-level, adaptable methodology that aggregates measurements of agri
      environmental indicators based on Multi-Criteria Analysis (MCA) techniques. The
      method was developed specifically to allow assessment of differences in the
      environmental performance of farms according to participation in agri-environment
      schemes. The AFI methodology is constructed so that high values represent good
      environmental performance. This paper explores the use of the AFI methodology in
      combination with Farm Business Survey data collected in England for the Farm
      Accountancy Data Network (FADN), to test whether its use could be extended for
      the routine surveillance of environmental performance of farming systems using
      established data sources. Overall, the aim was to measure the environmental
      impact of three different types of agriculture (arable, lowland livestock and
      upland livestock) in England and to identify differences in AFI due to
      participation in agri-environment schemes. However, because farm size, farmer
      age, level of education and region are also likely to influence the environmental
      performance of a holding, these factors were also considered. Application of the
      methodology revealed that only arable holdings participating in agri-environment
      schemes had a greater environmental performance, although responses differed
      between regions. Of the other explanatory variables explored, the key factors
      determining the environmental performance for lowland livestock holdings were
      farm size, farmer age and level of education. In contrast, the AFI value of
      upland livestock holdings differed only between regions. The paper demonstrates
      that the AFI methodology can be used readily with English FADN data and therefore
      has the potential to be applied more widely to similar data sources routinely
      collected across the EU-27 in a standardised manner.

PMID- 21075507
TI  - Past climate, future perspective: an exploratory analysis using climate proxies
      and drought risk assessment to inform water resources management and policy in
      Maine, USA.
AB  - In recent decades, significant progress has been made toward reconstructing the
      past climate record based on environmental proxies, such as tree rings and ice
      core records. However, limited examples of research that utilizes such data for
      water resources decision-making and policy exist. Here, we use the reconstructed
      record of Palmer Drought Severity Index (PDSI), dating back to 1138AD to
      understand the nature of drought occurrence (severity and duration) in the state
      of Maine. This work is motivated by the need to augment the scientific basis to
      support the water resources management and the emerging water allocation
      framework in Maine (Maine Department of Environmental Protection, Chapter 587).
      Through a joint analysis of the reconstructed PDSI and historical streamflow
      record for twelve streams in the state of Maine, we find that: (a) the
      uncertainties around the current definition of natural drought in the Chapter 587
      (based on the 20th century instrumental record) can be better understood within
      the context of the nature and severity of past droughts in this region, and (b) a
      drought index provides limited information regarding at-site hydrologic
      variations. To fill this knowledge gap, a drought index-based risk assessment
      methodology for streams across the state is developed. Based on these results,
      the opportunities for learning and challenges facing water policies in a changing
      hydroclimate are discussed.

PMID- 21075508
TI  - Ecotoxicological diagnosis of a sealed municipal landfill.
AB  - Assessing the environmental impact of a soil-topped landfill requires an accurate
      ecotoxicological diagnosis. This paper describes various diagnostic protocols for
      this purpose and their application to a real case: the urban solid waste (USW)
      municipal landfill of Getafe (Madrid, Spain). After their initial sealing with
      soil from the surroundings about 20 years ago, most USW landfills in the
      autonomous community of Madrid have continued to receive waste. This has hindered
      precise assessment of their impact on their environment and affected ecosystems.
      The procedure proposed here overcomes this problem by assessing the situation in
      edaphic, aquatic and ecological terms. The present study focused on the most
      influential soil variables (viz. salinity due largely to the presence of anions,
      and heavy metals and organic compounds). These variables were also determined in
      surface waters of the wetland most strongly affected by leachates running down
      landfill slopes. Determinations included the characterization of plant
      communities and microbial biodiversity. The study was supplemented with a
      bioassay under controlled conditions in pots containing soil contaminated with
      variable concentrations of Zn (as ZnCl(2)) intended to assess ecochemical actions
      in a population of Bromus rubens, which grows profusely in the landfill.

PMID- 21075509
TI  - Static and pulsatile intracranial pressure in idiopathic intracranial
      hypertension.
AB  - OBJECTIVE: The aim of this observational study was to characterize the static and
      pulsatile intracranial pressure (ICP) in conservatively (medically) treated
      idiopathic intracranial hypertension (IIH) patients in need of shunt surgery, and
      also in patients with chronic daily headache (CDH) without visual disturbances.
      METHODS: The material includes 14 IIH patients and 7 CDH patients in whom ICP was
      monitored continuously over-night. Static ICP was characterized by mean ICP,
      pulsatile ICP was characterized by the wave amplitude, rise time, and rise time
      coefficient. RESULTS: In the IIH group all 14 had headache and visual
      disturbances. Mean ICP was high (> 15 mmHg) in only 7 patients (50%), while mean
      ICP wave amplitude was high (>= 4 mmHg) in all 14 (100%). All IIH patients were
      shunted and improved clinically thereafter (i.e., relief from visual disturbances
      and/or headache). None in the CDH group had high mean ICP or mean ICP wave
      amplitude, and none were shunted. CONCLUSIONS: In this cohort of 14
      conservatively treated IIH patients with lasting and shunt-responsive headache
      and visual disturbances, the mean ICP wave amplitude was elevated (>= 4 mmHg) in
      all patients despite normal mean ICP (< 15 mmHg) in 7 patients (all but one on
      medication). Therefore, the pulsatile ICP may be more relevant than the static
      ICP in the diagnostic setting for patients with IIH. Further prospective
      standardized approaches are warranted.

PMID- 21075510
TI  - Spontaneous intracerebral hemorrhage associated with ingestion of isometheptine
      containing anti-migraine medication.

PMID- 21075511
TI  - Monitoring of cerebrospinal fluid flow by intraoperative ultrasound in patients
      with Chiari I malformation.
AB  - OBJECTIVE: To investigate the feasibility of intraoperative ultrasound (IOUS) for
      monitoring cerebrospinal fluid (CSF) flow in patients with Chiari I malformation.
      METHODS: Twenty patients with Chiari I were scanned by IOUS with color Doppler
      flow imaging (CDFI). CSF flow status and flow velocity were monitored at
      different times during the surgery. RESULTS: CSF flow was detected in all 20
      cases by IOUS-CDFI in real time. CSF flow was extremely slow or even ceased
      following bony decompression (craniectomy+laminectomy) in 19 patients; however,
      bi-directional flow was observed in the systolic phase and cranially directed
      flow in the diastolic phase. The maximum flow rate ranged from 4 to 13cm/s after
      duraplasty, and this varied with respiratory rhythm. Only 1 patient showed
      typical CSF flow after craniectomy, suggesting sufficient decompression, and
      without further duraplasty. All surgeries were terminated when bi-directional CSF
      flow was observed using IOUS-CDFI. With the exception of 1 patient, all the
      patients' symptoms were significantly relieved. CONCLUSION: IOUS-CDFI can monitor
      CSF flow during posterior fossa decompression, provide information about the re
      circulation of CSF flow, and objectively evaluate the efficacy of surgery.

PMID- 21075514
TI  - Valorisation of different types of boron-containing wastes for the production of
      lightweight aggregates.
AB  - Four boron-containing wastes (BW), named as Sieve (SBW), Dewatering (DBW),
      Thickener (TBW) and Mixture (MBW) waste, from Kirka Boron plant in west Turkey
      were investigated for the formation of artificial lightweight aggregates (LWA).
      The characterisation involved chemical, mineralogical and thermal analyses as
      well as testing of their bloating behaviour by means of heating microscopy. It
      was found that SBW and DBW present bloating behaviour whereas TBW and MBW do not.
      Following the above results two mixtures M1 and M2 were prepared with (in wt.%):
      20 clay mixture, 40 SBW, 40 DBW and 20 clay mixture, 35 SBW, 35 DBW, 10 quartz
      sand, respectively. Two different firing modes were applied: (a) from room
      temperature till 760  degrees C and (b) abrupt heating at 760  degrees C. The
      obtained bulk density for M1 and M2 pellets is 1.2g/cm(3) and 0.9 g/cm(3),
      respectively. The analysis of microstructure with electron microscopy revealed a
      glassy phase matrix and an extended formation of both interconnected and
      isolated, closed pores. The results indicate that SBW and DBW boron-containing
      wastes combined with a clay mixture and quartz sand can be valorised for the
      manufacturing of lightweight aggregates.

PMID- 21075513
TI  - Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a
      novel strategy in treating human epithelial ovarian cancer.
AB  - The purpose of this study was to investigate the in vitro effect of anti-MUC1
      monoclonal antibody (MAb) C595 alone and in combination with docetaxel, on the
      growth and survival of different epithelial ovarian cancer (EOC) cell lines. MUC1
      expression was assessed on EOC cell lines (OVCAR-3, IGROV-1, A2780, CAOV-3, TOV
      21G, TOV-112D, SKOV-3 and OV-90) using immunofluorescence labeling and flow
      cytometry. The effect of MAb C595 alone or in combination with docetaxel on the
      cell lines was studied by proliferation, colony and TUNEL assays. Our results
      indicate that all primary and metastatic EOC cell lines tested were positive to
      MAb C595 (MUC1); MAb C595 inhibited EOC cell proliferation in a MUC1- and dose
      dependent manner; low-dose MAb C595 (1/2 of IC50) combined with docetaxel greatly
      improved efficiency of cell killing in EOC cells and induced apoptosis; the
      additive effect of MAb C595 was further confirmed in colony forming assays; and
      cell death following single or combined treatments was associated with the
      release of cytochrome c and increased caspase-3 activity. These results suggest
      that MAb C595 used either alone, or combined with docetaxel, is an attractive
      strategy for targeting human EOC.

PMID- 21075512
TI  - Genomic instability and cancer: lessons learned from human papillomaviruses.
AB  - High-risk HPV E6 and E7 oncoproteins cooperate to subvert critical host cell
      cycle checkpoint control mechanisms in order to promote viral genome replication.
      This results not only in aberrant proliferation but also in host cellular changes
      that can promote genomic instability. The HPV-16 E7 oncoprotein was found to
      induce centrosome abnormalities thereby disrupting mitotic fidelity and
      increasing the risk for chromosome missegregation and aneuploidy. In addition,
      expression of the high-risk HPV E7 oncoprotein stimulates DNA replication stress
      as a potential source of DNA breakage and structural chromosomal instability.
      Proliferation of genomically unstable cells is sustained by several mechanisms
      including the accelerated degradation of claspin by HPV-16 E7 and the degradation
      of p53 by the high-risk HPV E6 oncoprotein. These results highlight the oncogenic
      potential of aberrant proliferation and opens new avenues for prevention of
      malignant progression, not only in HPV-associated cervical cancer but also in non
      virally associated malignancies with disrupted cell cycle checkpoint control
      mechanisms.

PMID- 21075515
TI  - Effect of saw dust on borate removal from groundwater in bench-scale simulation
      of permeable reactive barriers including magnesium oxide.
AB  - Effective immobilization of boron in groundwater is a major challenge. Permeable
      reactive barrier (PRB) column tests for removal of borate have been investigated
      using MgO agglomerates as the primary reactive material over 40 weeks.
      Additionally, saw dust was also blended with MgO agglomerates to facilitate for
      borate removal in this system. Boron accumulation was more than 1.6 times greater
      in the presence of saw dust, although MgO alone performed well. Increased boron
      accumulation in the presence of saw dust was primarily due to higher porosity of
      the PRB column, decreasing the impact of secondary Mg(OH)(2) passivating layers
      and leaving more reactive sites on MgO agglomerates. In addition, Mg(2+) ions
      released from MgO agglomerates are complexed with carboxylic acids leached from
      saw dusts. This sequestration prevents the formation of bulky Mg(OH)(2) which is
      an ineffective sorbent for borate and covers the surfaces and passivating
      reactive sites on the MgO agglomerates. The morphologies of Mg(OH)(2)
      precipitated in the PRB column were also significantly affected by the presence
      of saw dust, with crystallization of needle-like particles of Mg(OH)(2) was
      prevented by Mg(2+) ions-organic ligand complexation.

PMID- 21075516
TI  - Photocatalytic reduction of Cr(VI) on the novel hetero-system CuFe(2)O(4)/CdS.
AB  - The photocatalytic HCrO(4)(-) reduction was investigated in air equilibrated
      solution using the spinel CuFe(2)O(4) nanoparticles as sensitizers. The oxide is
      p-type semi conductor, prepared from nitrates decomposition. The catalytic
      performance increases with decreasing pH and the concomitant oxidation of
      salicylic acid contributes significantly to the photoactivity through the charges
      separation of electron/hole pairs (C(7)H(6)O(3)+6 O(2)+4h(+)+3 H(2)O -> 7 CO(2)+4
      H(3)O(+)). Evidence has been given to show the advantages of the hetero-system
      CuFe(2)O(4)/CdS in the chromate reduction. CuFe(2)O(4) acts as electrons pump and
      the electron transfer to chromate is mediated via CdS hexagonal variety
      (greenockite). A reduction of 60% occurs and the process is well described by a
      pseudo first order kinetic with a half life of ~2.8h and a quantum yield of
      ~0.12% for an initial HCrO(4)(-) concentration of 3 * 10(-4)M. An improvement up
      to 72% is obtained when the reaction occurs in a stirred reactor and no cadmium
      was detected after 6h illumination. The results indicate a competitive effect
      with the water reduction. The hydrogen evolutions are found to be 0.236 and 0.960
      cm(3)mn(-1)g(-1) in presence and in absence of HCrO(4)(-), respectively.

PMID- 21075517
TI  - Oxalate enhanced mechanism of hydroxyl-Fe-pillared bentonite during the
      degradation of Orange II by UV-Fenton process.
AB  - An enhanced method of hydroxyl-Fe-pillared bentonite (H-Fe-P-B) during the
      degradation of Orange II was studied to provide novel insight to interactions of
      degradation intermediates with heterogeneous catalyst in UV-Fenton system. Based
      on the degradation mechanism of Orange II, oxalate enhanced mechanism of H-Fe-P-B
      in heterogeneous UV-Fenton system was developed. The results showed that
      additional oxalate could increase the Fe leaching of H-Fe-P-B during
      heterogeneous UV-Fenton process, which led to higher mineralization efficiency of
      Orange II and lower energy consumption of treatment. When the concentrations of
      additional sodium oxalate increased up to 0.1 mmol L(-1), 0.2 mmol L(-1) and 0.4
      mmol L(-1), the rate of Orange II degradation could increase 30%, 46% and 63%,
      respectively. The iron ions leached from catalyst could be adsorbed back to the
      catalyst again after the organic intermediates were mineralized completely. Then
      the catalyst of H-Fe-P-B could be reused and additional pollution caused by iron
      ions could be avoided.

PMID- 21075518
TI  - Removal mechanisms of H(2)S using exhausted carbon in biofiltration.
AB  - Exhausted carbon which comes from the H(2)S adsorption process may be a hazardous
      waste. In this study, exhausted carbon was re-used in biofiltration for H(2)S
      removal. Two identical columns were used for exhausted carbon (Column A) and
      fresh carbon (Column B). They were operated in the same mode with 35 ppmv of
      H(2)S gas at an empty bed residence time (EBRT) of 10s. The results show that the
      removal efficiency of H(2)S in the two columns was almost identical at 95-100%.
      The removal mechanisms of H(2)S was explored and explained by developing a
      mathematical model. The model incorporated mass transfer, biodegradation,
      adsorption, as well as biofilm growth. The developed model can predict the
      experimental results very well. The modeled results suggest that the removal of
      H(2)S in Column A was attributed to the adsorption mechanism much less than in
      Column B during the start-up stage, while the removal of H(2)S by the
      biodegradation in Column A was much higher. The removal of H(2)S by the
      adsorption was significantly affected by the biodegradation. The simulation
      results also suggest that column A achieved the steady-state biodegradation in a
      shorter time than in Column B. This could result from higher biomass
      concentration of biofilm in Column A, due to the extra sulfur source from pre
      adsorbed sulfur on exhausted carbon besides H(2)S gas feeding.

PMID- 21075519
TI  - Analysis of antifouling agents after regulation of tributyltin compounds in
      Korea.
AB  - Diverse new antifouling agents are being used as replacements for the organotin
      compounds that are currently being banned. A comprehensive study on Korea's major
      seaports was conducted between 2006 and 2009 to assess the concentrations of
      butyltin compounds and new antifouling agents (chlorothalonil, dichlofluanid,
      Irgarol 1051). The constituents of the pollution due to antifouling agents in
      major seaports on the Korean peninsula are shifting from butyltin compounds to
      new antifouling agents. Also, the distribution of traditional butyltin compounds
      has centered on the east and west coasts, and the new antifouling agents have
      polluted the south and east coasts. With the results of this study, our lab was
      able to identify key locations within Korea where focused pollution control of
      antifouling agents is necessary.

PMID- 21075520
TI  - Nitrate reduction in water: influence of the addition of a second metal on the
      performances of the Pd/CeO(2) catalyst.
AB  - An attempt is made to improve the catalytic nitrate reduction on Pd/CeO(2)
      catalysts by the addition of a second metal. The influence of the second metal
      such as Sn, In and Ag on the Pd/CeO(2) for nitrate reduction is explored. The
      second metal is introduced over monometallic Pd/CeO(2) by a redox reaction.
      Pd/CeO(2) is more active than the bimetallic catalysts under pure hydrogen flow.
      Whereas in presence of CO(2) the monometallic Pd/CeO(2) is inactive for nitrate
      reduction, bimetallic catalysts are found to be more active than under pure
      hydrogen flow and also than the monometallic catalyst with a low selectivity
      towards ammonium ions, undesired product of the reaction. The Pd-Sn/CeO(2)
      catalyst is comparatively the most suited for nitrate reduction.

PMID- 21075521
TI  - Coagulation characteristics of titanium (Ti) salt coagulant compared with
      aluminum (Al) and iron (Fe) salts.
AB  - In this study, the performance of titanium tetrachloride (TiCl(4)) coagulation
      and flocculation is compared with commonly used coagulants such as aluminum
      sulfate (Al(2)(SO(4))(3)), polyaluminum chloride (PACl), iron chloride (FeCl(3)),
      and polyferric sulfate (PFS) in terms of water quality parameters and floc
      properties. TiCl(4) flocculation achieved higher removal of UV(254) (98%),
      dissolved organic carbon (DOC) (84%) and turbidity (93%) than other conventional
      coagulants. Charge neutralization and physical entrapment of colloids within
      coagulant precipitates and adsorption, seemed to play a significant role during
      TiCl(4) flocculation, while the main mechanism for conventional coagulants was
      bridge-aggregation and adsorption. The aggregated flocs after TiCl(4)
      flocculation showed the fastest growth rate compared to the other coagulants,
      with the largest floc size (801 MUm) occurring within 8 min. The floc strength
      factor of PACl, Al(2)(SO(4))(3), PFS, FeCl(3) and TiCl(4) was 34, 30, 29, 26 and
      29, respectively, while the floc recovery factor of the TiCl(4) coagulant was the
      lowest. Based on the results of the above study, it is concluded that the TiCl(4)
      flocculation can reduce the hydraulic retention time of slow and rapid mixing,
      however, careful handling of sludge is required due to the low recoverability of
      the aggregated floc.

PMID- 21075523
TI  - A prospective study of neuropathic pain induced by thoracotomy: incidence,
      clinical description, and diagnosis.
AB  - This study evaluated prospectively the incidence of neuropathic pain after
      thoracotomy, described its clinical characteristics, and delineated landmarks for
      its diagnosis in daily practice. We evaluated clinically painful symptoms and
      sensory deficits in 54 patients after lateral/posterolateral thoracotomy for
      broncho-pulmonary carcinoma with standardized surgical and analgesic procedures.
      At 2months, 49 patients suffered from non malignant thoracic pain, and at 6months
      38 patients (loss to follow-up for 7) reported persisting pain. In 35 patients,
      painful symptoms and sensory deficits could be evaluated using a standardized
      clinical bedside procedure. According to the grading system proposed by Treede et
      al. [41], neuropathic pain was considered probable in 21 patients, while use of
      the DN4 questionnaire concluded that neuropathic pain was probable in 17
      patients. The two diagnostic procedures provided similar conclusions in 16
      patients. Morphine consumption during the early post-operative period (mean
      111.3+/-30.8mg/day) and pain intensity (VAS: mean 5.71+/-2.1) were significantly
      higher in patients suffering from neuropathic pain than in other patients with
      pain (mean 80+/-21.4mg/day; VAS: mean 3.9+/-2.4). The clinical picture in most
      patients with neuropathic pain included electric shocks and severe multimodal
      hypoesthesia in the sensory area of 5th/6th intercostal nerves. Thus, our results
      indicate a minimal incidence of chronic post-thoracotomy pain at 70% and that of
      neuropathic pain at 29%, this latter being clinically suggested by a combination
      of certain symptoms and reinforced by the DN4 questionnaire when sensory deficit
      at scar is present.

PMID- 21075524
TI  - Brachylaima aspersae n. sp. (Digenea: Brachylaimidae) infecting farmed snails in
      NW Spain: morphology, life cycle, pathology, and implications for heliciculture.
AB  - The life cycle of Brachylaima aspersae n. sp. (Trematoda: Brachylaimidae) in
      heliciculture farms is elucidated in light of field and experimental studies.
      Embryonated asymmetrical eggs (33.3 MUm * 20.2 MUm) are passed in the faeces of
      the definitive host, the domestic mouse (Mus musculus), and are ingested by its
      unique first intermediate host, the helicid snail Helix aspersa aspersa. After
      hatching, the miracidium develops into a highly branched sporocyst in the
      connective tissues of the digestive gland. Microcaudate cercariae emerging from
      this gastropod migrate up the ureter of the second intermediate host, the snails
      H. a. aspersa and H. a. maxima, and develop into non-encysted metacercariae in
      the kidney. Following predation of infected snails, the metacercariae develop
      into adults preferentially in the proximal portion of the duodenum of the
      definitive host. The strict oioxenic character for the first intermediate host,
      as well as the cercarial chaetotaxy (3 C(I)V+1 C(I)D, 10 C(II), 5 C(III)V, 14
      C(III)L, 2 C(III)D, 16 H, 6 S(I), 6 S(II), 6 S(III), 2 A(I)L+1 A(I)V, 1 A(II)L, 3
      ML, 1 P(I)L and 3 P(III)L), the distinct pars prostatica, the variable appearance
      of testes (rounded to irregular, with smooth or slightly to moderately lobulated
      margins), the size of eggs, the position of acetabulum (located somewhat
      posterior to the anterior third of body), and the microhabitat of the adult in
      the final host allow differentiation of B. aspersae from other well-known species
      in the genus. Massive infections with sporocysts or metacercariae of this
      brachylaimid may induce extensive pathological changes in the organs affected.
      Our results confirm that control of rodents in heliciculture farms is essential
      to minimize the potential health risks and morbimortality associated with this
      newly described species.

PMID- 21075522
TI  - TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation.
AB  - The TRPA1 receptor is a member of the transient receptor potential (TRP) family
      of ion channels expressed in nociceptive neurons. TRPA1 receptors are targeted by
      pungent compounds from mustard and garlic and environmental irritants such as
      formaldehyde and acrolein. Ingestion or inhalation of these chemical agents
      causes irritation and burning in the nasal and oral mucosa and respiratory
      lining. Headaches have been widely reported to be induced by inhalation of
      environmental irritants, but it is unclear how these agents produce headache.
      Stimulation of trigeminal neurons releases CGRP and substance P and induces
      neurogenic inflammation associated with the pain of migraine. Here we test the
      hypothesis that activation of TRPA1 receptors is the mechanistic link between
      environmental irritants and peptide-mediated neurogenic inflammation. Known TRPA1
      agonists and environmental irritants stimulate CGRP release from dissociated rat
      trigeminal ganglia neurons and this release is blocked by a selective TRPA1
      antagonist, HC-030031. Further, TRPA1 agonists and environmental irritants
      increase meningeal blood flow following intranasal administration. Prior dural
      application of the CGRP antagonist, CGRP(8-37), or intranasal or dural
      administration of HC-030031, blocks the increases in blood flow elicited by
      environmental irritants. Together these results demonstrate that TRPA1 receptor
      activation by environmental irritants stimulates CGRP release and increases
      cerebral blood flow. We suggest that these events contribute to headache
      associated with environmental irritants.

PMID- 21075525
TI  - The transport of albendazole and albendazole sulphoxide in the lancet fluke
      (Dicrocoelium dendriticum).
AB  - Albendazole (ABZ) is one of the most important benzimidazole compounds possessing
      high activity against the lancet fluke, Dicrocoelium dendriticum. ABZ sulphoxide
      (ABZ.SO) is the main molecule present in the bloodstream of an ABZ-treated host.
      The aim of this study was to characterise the pattern of ex vivo uptake of ABZ
      and ABZ.SO by lancet flukes and the export of both anthelmintics from these
      parasites. Transport of these anthelmintics in both living and dead flukes was
      compared. The adult flukes were collected from mouflons (Ovis musimon) which had
      been infected naturally. Results showed that more lipophilic ABZ was imported to
      a higher extent than ABZ.SO, and that significantly higher concentrations of ABZ
      were detected within living flukes as compared to dead ones. The same pattern was
      revealed in the study of ABZ and ABZ.SO export from the flukes' bodies. In
      addition to passive diffusion, active ABZ uptake and active efflux of ABZ and
      ABZ.SO in D. dendriticum could be assumed.

PMID- 21075526
TI  - Molecular characterization of Cryptosporidium in Brazilian sheep.
AB  - Feces were collected from 125 sheep between January and December 2007, on ten
      farms in the State of Rio de Janeiro, Brazil, and examined for the presence of
      Cryptosporidium. Ninety samples were collected from lambs 2 to 6 months of age,
      and 35 were from sheep over 12 months of age. All samples were subjected to
      molecular analysis by polymerase chain reaction (nested PCR) in two steps of the
      SSU rRNA. Two samples (1.6%) from the lambs were positive, and after sequencing
      were identified as Cryptosporidium ubiquitum. This species has been reported
      worldwide and it is considered a zoonotic pathogen since it has been found and in
      several animal species and humans. However, because of the low frequency of C.
      ubiquitum found, the risk for public health in this region may not be high.

PMID- 21075527
TI  - Real-time polymerase chain reaction based on msa2c gene for detection of Babesia
      bovis.
AB  - This paper reports a quantitative real-time polymerase chain reaction (q-PCR)
      based on the msa2c gene and standardized with Platinum SYBR Green/ROX for the
      detection of Babesia bovis in cattle. The msa2c q-PCR amplified a DNA fragment
      with average dissociation temperature of 77.41 degrees C (+/- 0.25 degrees C). No
      amplification was detected when DNA from B. bigemina, A. marginale or Bos taurus
      was used as the template. The detection limit of the msa2c q-PCR was 1000 copies
      per ml of blood sample, with a linear correlation between the number of msa2c
      copies and threshold cycle. The comparison between msa2c q-PCR and conventional
      PCR for cytochrome b revealed 88.8% agreement, with a Kappa index of 0.75. In the
      comparison between msa2c q-PCR and an enzyme-linked immunosorbent assay (ELISA)
      with semi-purified B. bovis antigen, agreement was 96.3% and the Kappa index was
      0.91. The agreement between three tests was 85.8%. The msa2c q-PCR detected a
      higher number of positive cattle than conventional PCR in an enzootically stable
      area, but did not differ significantly from ELISA. No significant differences
      were detected between the three diagnostic tests with cattle from an enzootically
      unstable area. All animals raised on a tick-free facility were negative for B.
      bovis in the three tests. These results suggest that msa2c q-PCR is a useful test
      for the detection of B. bovis infection.

PMID- 21075528
TI  - The prevalence of Cryptosporidium spp. oocysts in wild mammals in the Kruger
      National Park, South Africa.
AB  - This study determined the prevalence of Cryptosporidium spp. oocysts in faecal
      samples from elephant (Loxodonta africana), buffalo (Syncerus caffer) and impala
      (Aepyceros melampus) in the Kruger National Park (KNP) and an adjacent game
      reserve in South Africa. Two of the study areas were in close proximity to rural
      communities on the western KNP boundary and the third study area was located in
      the centre of the KNP. Fresh stool samples (n=445) were collected and tested
      using an immunofluorescent antibody test (IFA) for Cryptosporidium parvum. A
      total of 278 of these were randomly selected (approximately 90 samples per
      wildlife species) and tested with the modified Ziehl Neelsen staining technique
      (ZN) for Cryptosporidium spp. The prevalence of Cryptosporidium spp. was highest
      in elephants (25.8% [95% confidence interval: 17.3, 35.9]), compared to buffalo
      (5.5% [1.8, 12.4]) and impala (4.3% [1.2, 10.5]). C. parvum showed similar
      patterns, being most prevalent in elephants (4.2% [1.5, 8.8]), compared to
      buffalo (1.4% [0.2, 5.1]) and impala (1.9% [0.4, 5.3]). 29 samples, including ZN
      positive and IFA positive samples, were retested using a real time PCR (rtPCR)
      technique. Of the 28 ZN-positive samples, 14 (50%) were positive with rtPCR and
      of the 9 IFA-positive samples 6 (67%) were confirmed positive by rtPCR. The
      prevalence of Cryptosporidium oocysts was significantly higher in both of the two
      study areas adjacent to the western KNP boundary compared to the area in the
      centre of the KNP (OR=3.2 [1.2, 9.0]; P=0.024). Our study demonstrates for the
      first time the presence of Cryptosporidium spp. in wildlife in South Africa. The
      transmission of this parasite between wildlife, domestic animals and humans is a
      plausible hypothesis and represents a potential risk for immunodeficient human
      populations.

PMID- 21075530
TI  - Allozyme markers suitable for population genetic analysis of Fasciola hepatica.
AB  - Protein electrophoresis was used to study allozyme variation in Fasciola hepatica
      collected from three locations in Galicia (NW Spain), an area where fascioliasis
      is endemic. Eleven of 16 loci showed variation in at least one population and 7
      loci were polymorphic in all populations studied. Five of these markers showed
      expected heterozygosities ranging from 0.137 to 0.569. The Nei's unbiased genetic
      diversity within populations ranged from 0.146 to 0.168. Genotypic frequencies
      were consistent with panmixia in 25 of 28 cases. Only 2 loci showed a significant
      deficit of heterozygotes. Genetic distances between populations were small
      (D(a)=0.003-0.010). These results suggest high levels of genetic variability and
      low population structure. This study shows that several of the markers developed
      are useful for study the population genetic structure of the parasite, which is
      essential to investigate the evolution of drug resistance that has recently
      emerged in populations of the study area.

PMID- 21075529
TI  - Evaluation of Toxoplasma gondii and Neospora caninum infections in sheep from
      Uberlandia, Minas Gerais State, Brazil, by different serological methods.
AB  - Toxoplasmosis and neosporosis have been recognized as economically important
      diseases with considerable impact on the livestock industry. Considering the
      scarce information on the occurrence of Toxoplasma gondii and Neospora caninum
      infections in sheep from Uberlandia, Minas Gerais State, Brazil, this study aimed
      to investigate the frequency of antibodies against these parasites in sheep sera
      from this region by using different serological methods. A total of 155 sheep
      serum samples were analyzed by the indirect fluorescence antibody test (IFAT) and
      enzyme-linked immunosorbent assay (ELISA) for the detection of IgG against T.
      gondii and N. caninum. Seroreactivity by IFAT showed 80% of samples with titers
      between 512 and 2048 for T. gondii (cutoff >= 64) and 78% presenting titers
      between 50 and 200 for N. caninum (cutoff >= 50). Seroreactivity by ELISA showed
      75% of samples with ELISA index (EI) between 2.0 and 3.0 for T. gondii (cutoff >=
      1.3) and 54% presenting EI between 1.3 and 2.0 for N. caninum (cut off >= 1.3).
      Discordant results by both tests were analyzed by immunoblot, resulting in a
      total seropositivity of 61% for T. gondii and 23% for N. caninum, with 41% to T.
      gondii only, 3% to N. caninum only, and 20% to both parasites. There was a
      significant positive association between seropositivity to T. gondii and age over
      one year (P<0.001), but such association was not found for N. caninum infection.
      In conclusion, as T. gondii and N. caninum infections are simultaneously present
      in sheep flocks of this region, it should be emphasized the importance to carry
      out a regular monitoring of Toxoplasma infection due to its high prevalence, its
      zoonotic potential and induction of reproductive disorders leading to economic
      losses. For neosporosis, sheep farmers should be instructed about the presence of
      the parasite in the flock, its risk factors and potential abortifacient role in
      sheep. Differential flock management could be valuable tool to establish the
      association of serological positivity and reproductive disease induced by N.
      caninum in sheep.

PMID- 21075531
TI  - Risk factors and control of intestinal parasite infections in sled dogs in
      Poland.
AB  - Training and racing constitute serious challenges for working sled dogs.
      Attainment of the highest levels of stamina and speed are possible only by
      completely healthy dogs. Infections with nematodes as whipworm Trichuris sp. or
      hookworms Uncinaria/Ancylostoma can significantly reduce the fitness of working
      dogs leading to anemia or even to death. In the middle of the racing season,
      between December 2009 and April 2010, 108 individual fecal samples were collected
      from 25 sled dog kennels situated in different regions of Poland. Saturated salt
      flotation was performed for helminth egg detection. The immunofluorescent assay
      MeriFluor Cryptosporidium/Giardia and nested PCRs on 18S rRNA (Cryptosporidium
      spp.) and TPI gene (Giardia spp.) were carried out for detection of intestinal
      protozoa. Overall prevalence of 6 species of intestinal parasites was 68% in sled
      dogs (73/108). In 51 samples the eggs of a single species of helminth were
      detected (47%), two nematode species were detected in 13%, three species of
      nematodes were found in two dogs. The most prevalent helminths were the hookworms
      Uncinaria/Ancylostoma-identified in 36% of kennels, and in 34% of sled dogs.
      Toxocara eggs were detected in 36% of kennels, in 17% of dogs. Trichuris sp. eggs
      were found in 20% of kennels (5/25), in 13% of dogs. Cysts/oocysts of intestinal
      protozoa were detected in 31% of sled dogs. The most prevalent was Giardia spp.
      infection-in 54% of kennels [13/24], in 28% of dogs. Cryptosporidium spp.
      infections were identified in 37.5% of kennels [9/24], in 13% of dogs. Two
      sequenced Giardia isolates presented 100% homology with G. intestinalis
      Assemblage C isolate (AY228641.1), specific for dogs. A range of factors was
      shown to affect the prevalence of intestinal parasites in sled dogs. The highest
      prevalence of parasites was found among dogs from large kennels (housing >3
      dogs), in dogs less than 2 years old, and in kennels, where prophylactic
      treatment was carried out 1-4 times a year. The present study has demonstrated a
      high prevalence of intestinal parasites in working sled dogs in Poland, including
      the zoonotic human pathogens Toxocara or Cryptosporidium.

PMID- 21075532
TI  - Improved detection of equine antibodies against Sarcocystis neurona using
      polyvalent ELISAs based on the parasite SnSAG surface antigens.
AB  - Equine protozoal myeloencephalitis (EPM) is a common neurologic disease of horses
      that is caused by the apicomplexan pathogen Sarcocystis neurona. To help improve
      serologic diagnosis of S. neurona infection, we have modified existing enzyme
      linked immunosorbent assays (ELISAs) based on the immunogenic parasite surface
      antigens SnSAG2, SnSAG3, and SnSAG4 to make the assays polyvalent, thereby
      circumventing difficulties associated with parasite antigenic variants and
      diversity in equine immune responses. Two approaches were utilized to achieve
      polyvalence: (1) mixtures of the individual recombinant SnSAGs (rSnSAGs) were
      included in single ELISAs; (2) a collection of unique SnSAG chimeras that fused
      protein domains from different SnSAG surface antigens into a single recombinant
      protein were generated for use in the ELISAs. These new assays were assessed
      using a defined sample set of equine sera and cerebrospinal fluids (CSFs) that
      had been characterized by Western blot and/or were from confirmed EPM horses.
      While all of the polyvalent ELISAs performed relatively well, the highest
      sensitivity and specificity (100%/100%) were achieved with assays containing the
      rSnSAG4/2 chimera (Domain 1 of SnSAG4 fused to SnSAG2) or using a mixture of
      rSnSAG3 and rSnSAG4. The rSnSAG4 antigen alone and the rSnSAG4/3 chimera (Domain
      1 of SnSAG4 fused to Domain 2 of SnSAG3) exhibited the next best accuracy at
      95.2% sensitivity and 100% specificity. Binding ratios and percent positivity
      (PP) ratios, determined by comparing the mean values for positive versus negative
      samples, showed that the most advantageous signal to noise ratios were provided
      by rSnSAG4 and the rSnSAG4/3 chimera. Collectively, our results imply that a
      polyvalent ELISA based on SnSAG4 and SnSAG3, whether as a cocktail of two
      proteins or as a single chimeric protein, can give optimal results in serologic
      testing of serum or CSF for the presence of antibodies against S. neurona. The
      use of polyvalent SnSAG ELISAs will enhance the reliability of serologic testing
      for S. neurona infection, which should lead to improved diagnosis of EPM.

PMID- 21075533
TI  - Evaluation of a TaqMan real-time PCR for the detection of Theileria parva in
      buffalo and cattle.
AB  - A real-time PCR assay based on TaqMan probe chemistry was developed for the
      detection of Theileria parva DNA in blood samples. It uses a Theileria genus
      specific PCR primer set and a T. parva-specific probe to amplify and hybridize
      with a species-specific part of the 18S rRNA gene of the parasite. The test was
      evaluated using positive and negative reference blood samples and shown to be
      specific for T. parva. Analytical sensitivity was determined by testing a
      dilution series of T. parva positive blood. It was shown to be able to detect
      parasitaemia as low as 2 * 10(-6)%. The Taqman assay results were also compared
      with that obtained with the real-time hybridization probe PCR assay, which is
      currently employed as the official test for the diagnosis of T. parva infections
      in buffalo and cattle and was shown to be equally sensitive. A panel of 1164
      field samples was screened using both assays and 164 samples tested positive in
      both tests, indicating a good correlation.

PMID- 21075535
TI  - Postburn perineal contractures: case reports from a Nigerian hospital.

PMID- 21075534
TI  - Pathological changes caused by Anoplocephala perfoliata in the mucosa/submucosa
      and in the enteric nervous system of equine ileocecal junction.
AB  - In this study, pathological changes caused by Anoplocephala perfoliata in the
      ileocecal junction were investigated in 31 regularly slaughtered mixed-breed
      horses of both sexes. Our results showed a significant relationship between
      parasite burden and grading of histopathological lesions in the mucosa and
      submucosa. Hypertrophy of the circular muscle layer was found in infected horses.
      Moreover, enteric nervous system evaluation showed a significant injury of
      intestinal nervous elements in the horses with moderate to high parasitism
      expressed as an increase of degenerative-regressive changes in neuronal cells and
      a decrease in the number of myenteric ganglia and neuronal cells. These findings
      can help to clarify the pathogenesis of intestinal motility disorders associated
      with A. perfoliata infection in horses.

PMID- 21075536
TI  - Optimizing Suprathel(r)-therapy by the use of Octenidine-Gel(r).
AB  - OBJECTIVE: A prospective, randomized, non-blinded, clinical study was conducted
      to evaluate the feasibility and practicability as well as pain reduction and ease
      of handling of Flammazine(r) versus Octenidine-Gel(r) s a primary local
      antiseptic before synthetic skin substitute application in partial-thickness
      burns. METHODS: Thirty patients with a median age of 42 years suffering from
      second-degree burns were included in the study. Burns were randomly selected, one
      area was treated with Flammazine(r)/gauze, another area in the same patient was
      treated with Octenidine-Gel(r)/gauze as initial antiseptic treatment. Within 24 h
      the first gauze change was performed followed by wound inspection, disinfection
      and synthetic skin substitute application. The study focused on patient pain
      score, analysis of wound bed and ease of handling of the two local antiseptic
      agents. RESULTS: There was a significant difference between Flammazine(r) versus
      Octenidine-Gel(r) regarding patient pain score and ease of handling. Octenidine
      Gel(r) was less painful (p < 0.05) and easier to handle (p < 0.05). There was no
      significant difference for wound bed evaluation between the two antiseptic
      agents. A tendency for better wound bed preparation was seen with the use of
      Octenidine-Gel(r). CONCLUSION: Based on the findings of this study Octenidine
      Gel(r) is recommended as a local antiseptic agent, because when compared to
      Flammazine(r), Octenidine-Gel(r) proved to be better in terms of ease of care,
      simplicity application, with gentler and faster detachment of the gel from wound
      surfaces and consequently far less pain during dressing changes.

PMID- 21075537
TI  - A comparative analysis of cetirizine, gabapentin and their combination in the
      relief of post-burn pruritus.
AB  - Post-burn pruritis is a very distressing symptom having a reported incidence
      between 80 and 100%. The mainstay of management of post-burn itch has been with
      antihistaminics and emollients but the treatment is ineffective in a very large
      percentage of patients. With the recognition of a distinct itch specific neuronal
      pathway, which has a complex interaction with pain pathway, a fresh approach to
      itch management has surfaced with the use of gabapentin. Gabapentin is an
      antiepileptic drug which has been successfully used to manage neuropathic pain,
      and is reporting to be successful in management of all forms of itch. With a
      paucity of randomized trials evaluating the role of gabapentin in post-burn itch
      management the current study was undertaken to individually evaluate gabapentin,
      cetirizine and their combination in relieving itch. Twenty patients were randomly
      recruited in each of the three groups and administered the respective drug(s) in
      doses determined by initial VAS (visual analog scale) scores. There was no
      significant difference in all the three groups with respect to mean age, sex
      distribution, mean percentage of TBSA burn and mean VAS score on day 0. VAS
      scores were evaluated over next 28 days (days 3, 7, 14, 21 and 28), and no
      emollients were prescribed for the study period. The initial mean VAS score
      reduced 95% in gabapentin group compared to 52% for the cetirizine group, which
      was highly significant (p<0.01). There was a 94% reduction in mean VAS score in
      the combination group which was comparable to the relief observed with gabapentin
      alone (p>0.05). Even the onset of action with gabapentin was significantly faster
      than the cetirizine group as evident from the mean VAS scores on day 3, which
      decreased 74% in gabapentin group compared to 32% in cetirizine group (p<0.01).
      Whereas all patients receiving gabapentin (either as monotherapy or in
      combination with cetirizine) reached an itch free status (VAS score 0-1) by day
      28 only 3/20 patients reached this level with cetirizine alone. It is quite
      evident from this study that gabapentin is significantly better than cetirizine
      as monotherapy in relieving post-burn itch and it also has a faster action. The
      hypothetical combination of a centrally acting drug with a peripherally acting
      agent did not result in any better control of post-burn itch than monotherapy
      with gabapentin. No side effects were reported with gabapentin administration but
      all patients receiving cetirizine reported sedation. There is now a need to
      relook at the antipruritic protocols in burn management.

PMID- 21075538
TI  - Androgen levels and anger and impulsivity measures as predictors of physical,
      verbal and indirect aggression in boys and girls.
AB  - Previous studies indicate that androgen levels and certain psychological
      characteristics such as anger and impulsivity are related to the development and
      maintenance of aggression. Further studies are required to analyze the potential
      predictor role of the interaction of said factors on aggressive behavior. 90 nine
      year-old children (44 boys and 46 girls) were assessed in relation to their
      levels of physical, verbal and indirect aggression, using a peer-rating
      technique. Testosterone and androstenedione levels were analyzed using an
      enzymoimmunoassay technique in saliva samples. Anger (state and trait) and anger
      control were measured using the STAXI-NA, and impulsivity was measured through
      the MFF-20. A General Linear Model revealed that sex was the best predictor for
      aggression measures, with boys scoring higher than girls in physical, verbal and
      indirect aggression; after sex, testosterone was found to be the best predictor
      (in a positive sense) of all three types of aggressive behavior studied. In
      addition to observing a main effect of androstenedione on physical and verbal
      aggression, a 'state anger*androstenedione' interaction was found to predict
      these types of aggression, with androstenedione acting as a moderator (inhibitor)
      of the effects of anger on these behaviors; also, a 'state anger*testosterone'
      interaction was found to predict verbal aggression. The results support the idea
      that, after sex, androgens constitute a biological marker to be taken into
      consideration in relation to individual differences in aggressive behavior. It is
      possible that at the age of 9, testosterone tends to increase aggression, while
      androstenedione tends to moderate (inhibit) the effects of anger on aggression.

PMID- 21075539
TI  - Disentangling two underlying processes in the initial phase of substance use:
      Onset and frequency of use in adolescent smoking.
AB  - PURPOSE: Most studies on adolescent smoking focus either on the probability of
      smoking onset or frequency of smoking. We assume the existence of two different
      qualitatively distinct processes in smoking acquisition. Therefore our objective
      was to test a two-part latent growth model, which assumes that psychosocial
      variables associated with the probability of smoking onset are different from, or
      differently related to variables associated with frequency of smoking given
      smoking onset. METHODS: The predictive associations of blocks of variables of (1)
      intrapersonal factors, (2) cognitions, (3) role models, and (4) family variables,
      on both smoking onset, and frequency of smoking given smoking onset, were tested
      in a nationwide sample of Dutch adolescents by using a two-part model. SUMMARY:
      Smoking onset was instigated by a variety of factors, while similar and other
      factors predicted frequency of smoking given smoking onset itself. Self-esteem,
      attitudes, and proportion of friends smoking, were identified as factors that
      affected both absolute smoking and frequency of smoking. OVERALL CONCLUSIONS:
      This study illustrates that it makes sense to differentiate between smoking onset
      and frequency of smoking and that few factors are active in both processes.

PMID- 21075540
TI  - Colchicine as a promising drug for Parkinson's disease.

PMID- 21075541
TI  - Recycling and reutilization of cytotoxic molecules, a new type of energy
      conservation of NK cells?
AB  - Natural killer (NK) cells play critical roles in defense against tumors and viral
      infections. They exert their cytotoxic functions through the secretion of
      granules containing cytotoxic molecules, such as perforin and granzymes. These
      cytotoxic molecules are stored within dual-functional organelles, known as
      secretory lysosomes. Target cell recognition induces the formation of an
      "immunological synapse", between the NK cell and its target, into which cytotoxic
      granules release their contents. However the post-exocytosis regulation of the
      process is still largely unknown. Recent research and the data accumulated
      therefrom lead to new hypotheses that suggest that, not unlike synaptic vesicle
      recycling in neuronal terminals, NK cells also recycle not just their secretory
      lysosome membranes but their correlated cytotoxic molecules (perforin and
      granzymes). The newly endocytosed vesicles are used to replenish the "reserve
      pool" of vesicles for continued NK cell serial killings. These hypotheses, if
      proved to be correct, will significantly improve our understanding of NK cell
      cytotoxicity mechanisms and might even suggest new NK cell-based therapies that
      rely on NK serial killing abilities for overcoming tumors.

PMID- 21075542
TI  - Rethinking chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex polygenic disease
      characterized by an abnormal inflammatory response to smoke, and results in a
      progressive and debilitating condition with declining lung function. The reasons
      why some smokers get COPD are not known. We suggest that corticosteroid
      resistance, which derives from oxidative stress, might actually be the cause of
      COPD and represent the starting point of the pathology. The absence of response
      to corticosteroids would let the disease develop, impairing the organism capacity
      to suppress any kind of inflammatory process. Corticosteroid resistance may
      derive from smoke induced oxidative stress and plausibly impairs the organism
      capacity to suppress inflammation. Many factors may contribute to the development
      and persistence of corticosteroid resistance: inefficient antioxidant defences, a
      corticosteroid response less efficient or more sensitive to oxidative conditions,
      and also any other concomitant factor, environmental, genetic or intercurrent,
      which would contribute to amplify inflammation and hence oxidative stress. One or
      more of these factors might represent the variable component of the disease,
      which gives origin to COPD heterogeneity. This hypotheses may also explain why
      the disease persists after quitting smoking, as an inflammatory process severe
      enough to generate a strong oxidative stress may support itself by maintenance of
      corticosteroid resistance.

PMID- 21075543
TI  - Possible roles of B lymphocyte activating factor of the tumour necrosis factor
      family in vitiligo autoimmunity.
AB  - Vitiligo is a cutaneous pigmentary disorder characterized by the loss of
      epidermal melanocytes. Strong evidence supports the theory that autoimmune
      mechanisms, namely B cell auto-antibody production and auto-reactive T cell
      cytotoxicity, are involved in this affliction. It is well known that autoimmunity
      results from a breakdown of self-tolerance. However, the mechanism which leads to
      the break-down of self-tolerance and subsequently causes the development of
      autoimmunity in vitiligo remains obscure. B lymphocyte activating factor of the
      tumour necrosis factor family is a recently identified ligand that is required
      for peripheral B-cell survival and homeostasis, the excessive production of which
      may lead to autoimmunity. Based on a collection of indirect evidences, we
      postulate that in individuals predisposed through inheritance, over-expression of
      the B lymphocyte activating factor may cause a breakdown of self-tolerance and
      subsequently cause autoimmune vitiligo via several possible mechanisms: B
      lymphocyte activating factor activates self-reactive B cells to produce auto
      antibodies against melanocytes; these B cells may function as cellular adjuvants
      for the activation of the CD4+ T cells, enhancing their helper effect on the
      activation of the CD8+ T cells; CD4+ T cells assist CD8+ T cells to respond to
      melanocytes antigen, leading to the autoreactive reaction; B lymphocyte
      activating factor activated B cells capture antigen and present it directly to
      the CD8+ T cells; and, B lymphocyte activating factor delivers a complete
      costimulation signal to the T cells (both CD4+ and CD8+ subset), playing an
      additional role in the autoimmune response in vitiligo. Future challenges remain
      to test these propositions. Advancement in the treatment of vitiligo is still
      unsatisfactory, and thus novel modalities of therapy need to be developed.
      Recently, B lymphocyte activating factor has been evaluated as an attractive
      target for immune therapy. Once the hypothesis of B lymphocyte activating factor
      mediating the breakdown of self-tolerance in vitiligo is corroborated, it can
      become a novel target for treatment of vitiligo.

PMID- 21075544
TI  - Necroptosis: a novel therapeutic target for glioblastoma.
AB  - Glioblastoma or glioblastoma multiforme (GBM) is the most encountered and
      malignant form of brain tumors in clinical practice. In spite of optimal and
      early treatment, the life expectancy of patients with GBM remains poor. It is
      believed that dysfunction of apoptosis underlies GBM tumorigenesis, proliferation
      and resistance to chemotherapy and radiotherapy. Although GBM is defective in
      apoptotic process, pathologic and radiologic observations almost always reveal
      obvious necrosis foci within GBM. Necrosis seems to be related with GBM
      proliferation, angiogenesis and invasion. However, tumor cell necrosis induced by
      various therapies has a potential therapeutic value. Just recently, necrotic cell
      death is considered as a regulated and controlled process, like apoptosis, termed
      necroptosis or programmed necrosis. Induction of apoptosis has not made any
      significant achievements in the treatment of GBM mainly because the tumor cells
      are apoptosis-resistant. We may achieve a better result by modulating the
      necroptosis of GBM thus circumvent the apoptosis resistance. Albeit specific
      molecular pathways involved in GBM necroptosis is not clear and much more studies
      are needed to confirm the effects of therapy-induced necroptosis on GBM, it
      provides us with a new direction in the treatment of GBM.

PMID- 21075545
TI  - Effect of restricted feeding and realimentation periods on pork quality and fatty
      acid profile of M. longissimus thoracis.
AB  - An experiment with 94 fattening pigs (48 gilts and 46 barrows) was conducted to
      determine the effect of feeding 25% restricted diets at different body weights on
      meat quality and fatty acid profile of M. longissimus thoracis (LT). During the
      84 days of the experiment (4 periods, 21 days each), animals with an initial
      weight of about 31 kg were fed in different periods of observation ad libitum (A)
      or restricted diets (R) in groups AAAA, AARA, RAAA and RARA. After 21 days of the
      experiment, the restricted-fed pigs, compared to those fed ad libitum, had a
      lower total fat content of M. longissimus thoracis (P<0.05), higher shear force
      (P=0.068), and lower proportions of SFA (C14:0, C18:0 P<0.05) and MUFA and higher
      proportions of PUFA (C20:4, C22:4 P<0.05) in the fatty acid profile. Three weeks
      after the restricted feed supply was lifted, the total fat content in LT muscle
      was higher than in animals fed ad libitum throughout (2.34 vs. 2.02), very close
      after the next 3 weeks of realimentation (3.16 vs. 3.15) and lower after another
      3 weeks (3.19 vs. 3.49). Regardless of the time at which restricted feeding was
      started and the number of restricted feeding periods, the total fat content in
      the LT muscle at the end of the experiment was similar or lower in groups RAAA,
      AARA and RARA, compared to group AAAA. The coefficient of correlation between the
      total fat content in LT and the shear force was -0.36 (P<0.01). Colour, pH and
      drip loss did not depend on the level of nutrition. After 84 days of observation,
      animals from groups RARA and AARA, compared to pigs from groups AAAA and RAAA,
      were characterized by a slightly higher shear force of LT, lower SFA and MUFA
      (P<0.001), and higher n-6 PUFA (P<0.01) and n-3 PUFA (P<0.01) proportions in the
      fatty acid profile. The fatty acid profiles of AAAA pigs and pigs undergoing a 63
      day realimentation period (RAAA) were similar. Regardless of the feeding scheme,
      the n-6:n-3 ratio exceeded 10 in all the groups.

PMID- 21075546
TI  - Effect of phosphate, ascorbic acid and alpha-tocopherol injected at one-location
      with tumbling on quality of roast beef.
AB  - The purpose of this study was to evaluate if continuous non-vacuum or vacuum
      tumbling improves the quality of roast beef utilizing the one location injection.
      Basically, fresh roast beef treated by one location injection with tumbling had
      significantly different quality compared to non-tumbled ones. However, the cooked
      roast beef did not significantly exhibit better quality due to tumbling. There
      was insignificant difference of TBARS value for whole meat among treatments at
      day 0. The control had significantly higher TBARS value compared to roast beef
      with non-vacuum and vacuum tumbled samples at day 2. At 4, 7 and 14 days of
      refrigerated storage, the control maintained the significantly highest values
      when compared to the other treatments that had similar TBARS values. The addition
      of three antioxidants was the major contributor to lipid stability of the cooked
      roast beef.

PMID- 21075547
TI  - Patient-specific Monte Carlo-based dose-kernel approach for inverse planning in
      afterloading brachytherapy.
AB  - PURPOSE: Brachytherapy planning software relies on the Task Group report 43
      dosimetry formalism. This formalism, based on a water approximation, neglects
      various heterogeneous materials present during treatment. Various studies have
      suggested that these heterogeneities should be taken into account to improve the
      treatment quality. The present study sought to demonstrate the feasibility of
      incorporating Monte Carlo (MC) dosimetry within an inverse planning algorithm to
      improve the dose conformity and increase the treatment quality. METHODS AND
      MATERIALS: The method was based on precalculated dose kernels in full patient
      geometries, representing the dose distribution of a brachytherapy source at a
      single dwell position using MC simulations and the Geant4 toolkit. These dose
      kernels are used by the inverse planning by simulated annealing tool to produce a
      fast MC-based plan. A test was performed for an interstitial brachytherapy breast
      treatment using two different high-dose-rate brachytherapy sources: the
      microSelectron iridium-192 source and the electronic brachytherapy source Axxent
      operating at 50 kVp. RESULTS: A research version of the inverse planning by
      simulated annealing algorithm was combined with MC to provide a method to fully
      account for the heterogeneities in dose optimization, using the MC method. The
      effect of the water approximation was found to depend on photon energy, with
      greater dose attenuation for the lower energies of the Axxent source compared
      with iridium-192. For the latter, an underdosage of 5.1% for the dose received by
      90% of the clinical target volume was found. CONCLUSION: A new method to optimize
      afterloading brachytherapy plans that uses MC dosimetric information was
      developed. Including computed tomography-based information in MC dosimetry in the
      inverse planning process was shown to take into account the full range of scatter
      and heterogeneity conditions. This led to significant dose differences compared
      with the Task Group report 43 approach for the Axxent source.

PMID- 21075549
TI  - Radiobiological characterization of two therapeutic proton beams with different
      initial energy spectra used at the Institut Curie Proton Therapy Center in Orsay.
AB  - PURPOSE: Treatment planning in proton therapy uses a generic value for the
      relative biological efficiency (RBE) of 1.1 throughout the spread-out Bragg peak
      (SOBP) generated. In this article, we report on the variation of the RBE with
      depth in the SOBP of the 76- and 201-MeV proton beams used for treatment at the
      Institut Curie Proton Therapy Center in Orsay. METHODS AND MATERIALS: The RBE
      (relative to (137)Cs gamma-rays) of the two modulated proton beams at three
      positions in the SOBP was determined in two human tumor cells using as endpoints
      clonogenic cell survival and the incidence of DNA double-strand breaks (DSBs) as
      measured by pulse-field gel electrophoresis without and with enzymatic treatment
      to reveal clustered lesions. RESULTS: The RBE for induced cell killing by the 76
      MeV beam increased with depth in the SOBP. However for the 201-MeV protons, it
      was close to that for (137)Cs gamma-rays and did not vary significantly. The
      incidence of DSBs and clustered lesions was higher for protons than for (137)Cs
      gamma-rays, but did not depend on the proton energy or the position in the SOBP.
      CONCLUSIONS: Until now, little attention has been paid to the variation of RBE
      with depth in the SOBP as a function of the nominal energy of the primary proton
      beam and the molecular nature of the DNA damage. The RBE increase in the 76-MeV
      SOBP implies that the tumor tissues at the distal end receives a higher
      biologically equivalent dose than at the proximal end, despite a homogeneous
      physical dose. This is not the case for the 201-MeV energy beam. The precise
      determination of the effects of incident beam energy, modulation, and depth in
      tissues on the linear energy transfer-RBE relationship is essential for treatment
      planning.

PMID- 21075550
TI  - Identification of a high-risk group among patients with oral cavity squamous cell
      carcinoma and pT1-2N0 disease.
AB  - PURPOSE: In the American Joint Committee on Cancer 2010 classification system,
      pT1-2N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage
      cancer treatable with surgery alone (National Comprehensive Cancer Network 2010
      guidelines). Our aim was to evaluate the feasibility of surgery alone for pT1-2N0
      OSCC patients. METHODS AND MATERIALS: Among 1279 previously untreated OSCC
      patients referred to our hospital between January 1996 and May 2008, we
      identified 457 consecutive patients with pT1-2N0 disease. All had radical tumor
      excision with neck dissection. A total of 387 patients showing pathologic margins
      greater than 4 mm and treated by surgery alone were included in the final
      analysis. All were followed up for at least 24 months after surgery or until
      death. The 5-year rates of control, distant metastasis, and survival were the
      main outcome measures. RESULTS: The 5-year rates in the entire group of pT1-2N0
      patients were as follows: local control, 91%; neck control, 92%; distant
      metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and
      overall survival, 84%. Multivariate analysis identified poor differentiation and
      pathologic tumor depth of 4 mm or greater as independent risk factors for neck
      control, disease-free survival, and disease-specific survival. A scoring system
      using poor differentiation and tumor depth was formulated to define distinct
      prognostic groups. The presence of both poorly differentiated tumors and a tumor
      depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p
      < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall
      survival (p = 0.0046) rates. CONCLUSION: The combination of poor differentiation
      and pathologic tumor depth of 4 mm or greater identified a subset of pT1-2N0 OSCC
      patients with poor outcome, who may have clinical benefit from postoperative
      adjuvant radiotherapy.

PMID- 21075548
TI  - Heterogeneity of disease classified as stage III in Wilms tumor: a report from
      the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).
AB  - PURPOSE: We analyzed whether the prognosis can differ among Wilms tumors (WT)
      labeled as Stage III according to currently adopted classification systems.
      METHODS AND MATERIALS: Patients with nonanaplastic Stage III WT consecutively
      registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)
      trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady
      mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy
      with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT).
      RESULTS: Ninety-nine WT patients met the criteria for classification as Stage III
      according to a revised version of the National Wilms Tumor Study-3 staging system
      (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were
      not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year
      disease-free survival (DFS) and overall survival (OS) rates were 85% +/- 4% and
      92% +/- 3%, respectively, for the whole group. For 38 children with positive LN,
      the 4-year DFS rate was 73% +/- 7%, as opposed to 98% +/- 2% for the 45 children
      with Stage III WT according to the other criteria but with negative biopsied LN
      (p = 0.001). The subgroup with the worst prognosis consisted of children more
      than 2 years old with positive LN (DFS 67% +/- 8%). A delay between surgery and
      RT > 30 days had an adverse impact on the abdominal tumor relapse rate.
      CONCLUSIONS: This study provides further evidence that Stage III tumors with LN
      metastases might be distinguished from WTs meeting the other criteria for
      classification as Stage III. The worse outcome of the former may warrant a
      prospective study on the effects of intensified therapy. A subclassification of
      Stage III tumors is discussed.

PMID- 21075552
TI  - Prognostic significance of human apurinic/apyrimidinic endonuclease (APE/Ref-1)
      expression in rectal cancer treated with preoperative radiochemotherapy.
AB  - PURPOSE: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair
      of radiation-induced DNA lesions and regulates transcription via redox-based
      activation. We investigated the predictive and prognostic significance of APE/Ref
      1 expression in pretreatment biopsy specimens in locally advanced rectal cancer
      (LARC) (cT3-T4 or N+). METHODS AND MATERIALS: APE/Ref-1 expression was analyzed
      by immunohistochemistry in pretreatment biopsy specimens obtained from 83
      patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28
      fractions, combined with oral capecitabine and leucovorin chemotherapy, followed
      by curative surgery. The prognostic significance of various clinicopathologic
      characteristics, including APE/Ref-1 protein expression, was evaluated. RESULTS:
      APE/Ref-1 was expressed in 97% of patient samples. Exclusive APE/Ref-1 nuclear
      staining was observed in 49 of 83 samples (59%), and mixed nuclear and
      cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear
      expression levels were low in 49 patients (59%) and high in 34 patients (41%).
      The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall
      and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline
      significant predictive factor for pathologic tumor response (p = 0.08) and a
      significant prognostic factor for disease-free survival, as shown by univariate
      analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic
      localization of APE/Ref-1 is a significant predictor of disease-free survival
      (hazard ratio, 0.45; p = 0.046). CONCLUSIONS: APE/Ref-1 was expressed in a
      majority of pretreatment biopsy specimens from patients with LARC. The level of
      APE/Ref-1 nuclear expression was not a significant predictive and prognostic
      factor; however, cytoplasmic localization of the protein was negatively
      associated with disease-free survival. These results indicate that cytoplasmic
      expression of APE/Ref-1 represents an adverse prognostic factor for LARC patients
      who receive preoperative radiochemotherapy.

PMID- 21075551
TI  - A phase II comparative study of gross tumor volume definition with or without
      PET/CT fusion in dosimetric planning for non-small-cell lung cancer (NSCLC):
      primary analysis of Radiation Therapy Oncology Group (RTOG) 0515.
AB  - BACKGROUND: Radiation Therapy Oncology Group (RTOG) 0515 is a Phase II
      prospective trial designed to quantify the impact of positron emission tomography
      (PET)/computed tomography (CT) compared with CT alone on radiation treatment
      plans (RTPs) and to determine the rate of elective nodal failure for PET/CT
      derived volumes. METHODS: Each enrolled patient underwent definitive radiation
      therapy for non-small-cell lung cancer (>= 60 Gy) and had two RTP datasets
      generated: gross tumor volume (GTV) derived with CT alone and with PET/CT.
      Patients received treatment using the PET/CT-derived plan. The primary end point,
      the impact of PET/CT fusion on treatment plans was measured by differences of the
      following variables for each patient: GTV, number of involved nodes, nodal
      station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean
      esophageal dose (MED). Regional failure rate was a secondary end point. The
      nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni
      adjustment for an overall significance level of 0.05. RESULTS: RTOG 0515 accrued
      52 patients, 47 of whom are evaluable. The follow-up time for all patients is
      12.9 months (2.7-22.2). Tumor staging was as follows: II = 6%; IIIA = 40%; and
      IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived
      volumes (98.7 vs. 86.2 mL; p < 0.0001). MLDs for PET/CT plans were slightly lower
      (19 vs. 17.8 Gy; p = 0.06). There was no significant difference in the number of
      involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy).
      Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has
      developed an elective nodal failure. CONCLUSIONS: PET/CT-derived tumor volumes
      were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in
      51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is
      quite low, supporting the RTOG standard of limiting the target volume to the
      primary tumor and involved nodes.

PMID- 21075553
TI  - Prophylaxis of radiation-induced nausea and vomiting using 5-hydroxytryptamine-3
      serotonin receptor antagonists: a systematic review of randomized trials.
AB  - PURPOSE: To systematically review the effectiveness and safety of 5
      hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other
      antiemetic medication or placebo for prophylaxis of radiation-induced nausea and
      vomiting. METHODS AND MATERIALS: We searched the following electronic databases:
      MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and
      Web of Science. We also hand-searched reference lists of included studies.
      Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic
      medication or placebo for preventing radiation-induced nausea and vomiting were
      included. We excluded studies recruiting patients receiving concomitant
      chemotherapy. When appropriate, meta-analysis was conducted using Review Manager
      (v5) software. Relative risks were calculated using inverse variance as the
      statistical method under a random-effects model. We assessed the quality of
      evidence by outcome using the Grading of Recommendations Assessment, Development,
      and Evaluation approach. RESULTS: Eligibility screening of 47 articles resulted
      in 9 included in the review. The overall methodologic quality was moderate. Meta
      analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs
      (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR
      0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs.
      metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control
      (RR 0.27, 95% CI 0.15-0.47). CONCLUSION: 5-Hydroxytryptamine-3 RAs are superior
      to placebo and other antiemetics for prevention of emesis, but little benefit was
      identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for
      prevention of emesis. Limited evidence was found regarding delayed emesis,
      adverse events, quality of life, or need for rescue medication. Future
      randomized, controlled trials should evaluate different 5-HT3 antiemetics and new
      agents with novel mechanisms of action such at the NK(1) receptor antagonists to
      determine the most effective drug. Delayed nausea and vomiting should be a focus
      of future study, perhaps concentrating on the palliative cancer population.

PMID- 21075554
TI  - A matched-case comparison to explore the role of consolidation chemotherapy after
      concurrent chemoradiation in cervical cancer.
AB  - PURPOSE: The aim of this study was to compare the efficacy and toxicity of
      consolidation chemotherapy after concurrent chemoradiation (CCRT) and CCRT alone
      in patients with locally advanced cervical carcinoma. METHODS AND MATERIALS:
      Using medical records from January 2001 to December 2007, 39 patients treated
      with consolidation chemotherapy after CCRT (Group 1) were matched to 39 patients
      treated with CCRT alone (Group 2). Consolidation chemotherapy consisted of three
      additional cycles of chemotherapy with cisplatin 60 mg/m2 (Day 1) and 5
      fluorouracil 1,000 mg/m2 per day (Days 1-5) given every 3 weeks. The primary
      endpoint was overall survival. RESULTS: During a median follow-up period of 35
      months (range, 8-96 months), 10 (25.6%) and 16 (41.0%) patients showed disease
      progression in Groups 1 and 2, respectively. Distant recurrence with or without
      locoregional/lymphogenous recurrence occurred more frequently in Group 2 than in
      Group 1 (23.1% vs. 7.7%, p=0.06). By contrast, there was no difference in
      locoregional or lymphogenous recurrence between the two groups. The rate of
      overall survival was higher in Group 1 than in Group 2 (92.7% vs. 69.9%,
      p=0.042), whereas the difference in progression-free survival between the groups
      was not statistically significant (70.1% vs. 55.1%, p=0.079). Although the
      difference was not statistically significant, neutropenia was more common in
      Group 1 than in Group 2 (10.9% vs. 4.7%, p=0.07). CONCLUSIONS: Consolidation
      chemotherapy after CCRT may improve survival and reduce distant recurrence
      without additional toxicity compared to CCRT alone in patients with locally
      advanced cervical carcinoma.

PMID- 21075555
TI  - Magnetic resonance lymphography-guided selective high-dose lymph node irradiation
      in prostate cancer.
AB  - PURPOSE: To demonstrate the feasibility of magnetic resonance lymphography (MRL) 
      guided delineation of a boost volume and an elective target volume for pelvic
      lymph node irradiation in patients with prostate cancer. The feasibility of
      irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes
      in conjunction with irradiation of the prostate using intensity-modulated
      radiotherapy (IMRT) was also investigated. METHODS AND MATERIALS: In 4 prostate
      cancer patients with a high risk of lymph node involvement but no enlarged lymph
      nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis.
      These lymph nodes were identified and delineated on a radiotherapy planning CT to
      create a boost volume. Based on the location of the MRL-positive lymph nodes, the
      standard elective pelvic target volume was individualized. An IMRT plan with a
      simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy
      to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes,
      and 72 Gy to the prostate. RESULTS: All MRL-positive lymph nodes could be
      identified on the planning CT. This information could be used to delineate a
      boost volume and to individualize the pelvic target volume for elective
      irradiation. IMRT planning delivered highly acceptable radiotherapy plans with
      regard to the prescribed dose levels and the dose to the organs at risk (OARs).
      CONCLUSION: MRL can be used to select patients with limited lymph node
      involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and
      an elective pelvic target volume for selective high-dose lymph node irradiation
      with IMRT is feasible. Whether this approach will result in improved outcome for
      these patients needs to be investigated in further clinical studies.

PMID- 21075556
TI  - The information needs of new radiotherapy patients: how to measure? Do they want
      to know everything? And if not, why?
AB  - PURPOSE: To establish 1) further psychometric properties of the information
      preference for radiotherapy patients scale (IPRP); 2) what information new
      radiotherapy patients want to receive; 3) which patients have a lower information
      need. METHODS AND MATERIALS: Eligible patients (n = 159; response rate 54%) of 15
      radiation oncologists completed the IPRP and provided background characteristics
      before their first radiotherapy consultation. Exclusion criteria were: age <18
      years, having undergone radiotherapy before, unable to read and write Dutch,
      cognitive problems or a brain tumor. RESULTS: Reliability (Cronbach's alpha 0.84
      0.97) and concurrent validity (r from .39 to .57, p < 0.001) of the subscales of
      the IPRP were good. New radiotherapy patients want extensive information about
      their disease, treatment, procedures, side effects, and prognosis (mean scores
      between 4.1 and 4.4 on a scale from 1 to 5) but less information about
      psychosocial issues (mean = 3.4). Patients who are older and male, have lung or
      rectal cancer, more difficulty understanding and a higher trait anxiety level,
      need less information. CONCLUSIONS: The IPRP can reliably and validly address
      information needs of patients undergoing radiation treatment. Most new
      radiotherapy patients want much information. Yet, information giving should be
      tailored according to their background, understanding and anxiety.

PMID- 21075557
TI  - Salivary gland tumors treated with adjuvant intensity-modulated radiotherapy with
      or without concurrent chemotherapy.
AB  - PURPOSE: To analyze the recent single-institution experience of patients with
      salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy
      (IMRT), with or without concurrent chemotherapy. PATIENTS AND METHODS: We
      performed a retrospective analysis of 35 salivary gland carcinoma patients
      treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with
      surgery and adjuvant IMRT. The primary endpoints were local control, progression
      free survival, and overall survival. The secondary endpoints were acute and
      chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2
      2.8) among the surviving patients. RESULTS: The histologic types included adenoid
      cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma
      in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary
      sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue
      in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose
      was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy
      regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for
      patients undergoing CRT to have more adverse prognostic factors, including Stage
      T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT,
      n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5,
      38%, p = .30). One patient who had undergone CRT developed an in-field
      recurrence, resulting in an overall actuarial 3-year local control rate of 92%.
      Five patients (14%) developed distant metastases (1 who had undergone IMRT only
      and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and
      dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%,
      and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4
      toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8,
      23%). CONCLUSIONS: Treatment of salivary gland malignancies with postoperative
      IMRT was well tolerated with a high rate of local control. Chemoradiotherapy
      resulted in excellent local control in a subgroup of patients with adverse
      prognostic factors and might be warranted in select patients.

PMID- 21075558
TI  - Radiation therapy after breast-conserving surgery: does hospital surgical volume
      matter? A population-based study in Taiwan.
AB  - PURPOSE: To examine the association between hospital surgical volume and the use
      of radiation therapy (RT) after breast-conserving surgery (BCS) in Taiwan.
      METHODS AND MATERIALS: We used claims data from the National Health Insurance
      program in Taiwan (1997-2005) in this retrospective population-based study. We
      identified patients with breast cancer, receipt of BCS, use of radiation, and the
      factors that could potentially associated with the use of RT from enrollment
      records, and the ICD-9 and billing codes in claims. We conducted logistic
      regression to examine factors associated with RT use after BCS, and performed
      subgroup analyses to examine whether the association differs by medical center
      status or hospital volumes. RESULTS: Among 5,094 patients with newly diagnosed
      invasive breast cancer who underwent BCS, the rate of RT was significantly lower
      in low-volume hospitals (74% vs. 82%, p < 0.01). Patients treated in low-volume
      hospitals were less likely to receive RT after BCS (odds ratio = 0.72, 95%
      confidence interval = 0.62-0.83). In addition, patients treated after the
      implementation of the voluntary pay-for-performance policy in 2001 were more
      likely to receive RT (odds ratio = 1.23; 95% confidence interval = 1.05-1.45).
      Subgroup analyses indicated that the high-volume effect was limited to hospitals
      accredited as non-medical centers, and that the effect of the pay-for-performance
      policy was most pronounced among low-volume hospitals. CONCLUSIONS: Using
      population-based data from Taiwan, our study concluded that hospital surgical
      volume and pay-for-performance policy are positively associated with RT use after
      BCS.

PMID- 21075559
TI  - Effect of immobilization and performance status on intrafraction motion for
      stereotactic lung radiotherapy: analysis of 133 patients.
AB  - PURPOSE: To assess intrafractional geometric accuracy of lung stereotactic body
      radiation therapy (SBRT) patients treated with volumetric image guidance. METHODS
      AND MATERIALS: Treatment setup accuracy was analyzed in 133 SBRT patients treated
      via research ethics board-approved protocols. For each fraction, a localization
      cone-beam computed tomography (CBCT) scan was acquired for soft-tissue
      registration to the internal target volume, followed by a couch adjustment for
      positional discrepancies greater than 3 mm, verified with a second CBCT scan.
      CBCT scans were also performed at intrafraction and end fraction. Patient
      positioning data from 2047 CBCT scans were recorded to determine systematic
      (Sigma) and random (sigma) uncertainties, as well as planning target volume
      margins. Data were further stratified and analyzed by immobilization method
      (evacuated cushion [n=75], evacuated cushion plus abdominal compression [n=33],
      or chest board [n=25]) and by patients' Eastern Cooperative Oncology Group
      performance status (PS): 0 (n=31), 1 (n=70), or 2 (n=32). RESULTS: Using CBCT
      internal target volume was matched within +/-3 mm in 16% of all fractions at
      localization, 89% at verification, 72% during treatment, and 69% after treatment.
      Planning target volume margins required to encompass residual setup errors after
      couch corrections (verification CBCT scans) were 4 mm, and they increased to 5 mm
      with target intrafraction motion (post-treatment CBCT scans). Small differences
      (<1 mm) in the cranial-caudal direction of target position were observed between
      the immobilization cohorts in the localization, verification, intrafraction, and
      post-treatment CBCT scans (p<0.01). Positional drift varied according to patient
      PS, with the PS 1 and 2 cohorts drifting out of position by mid treatment more
      than the PS 0 cohort in the cranial-caudal direction (p=0.04). CONCLUSIONS: Image
      guidance ensures high geometric accuracy for lung SBRT irrespective of
      immobilization method or PS. A 5-mm setup margin suffices to address
      intrafraction motion. This setup margin may be further reduced by strategies such
      as frequent image guidance or volumetric arc therapy to correct or limit
      intrafraction motion.

PMID- 21075560
TI  - Primary mucosa-associated lymphoid tissue lymphoma of the salivary glands: a
      multicenter Rare Cancer Network study.
AB  - PURPOSE: Involvement of salivary glands with mucosa-associated lymphoid tissue
      (MALT) lymphoma is rare. This retrospective study was performed to assess the
      clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of
      the salivary glands. METHODS AND MATERIALS: Thirteen member centers of the Rare
      Cancer Network from 10 countries participated, providing data on 63 patients. The
      median age was 58 years; 47 patients were female and 16 were male. The parotid
      glands were involved in 49 cases, submandibular in 15, and minor glands in 3.
      Multiple glands were involved in 9 patients. Staging was as follows: IE in 34,
      IIE in 12, IIIE in 2, and IV in 15 patients. RESULTS: Surgery (S) alone was
      performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4
      patients. Forty-one patients received combined modality treatment (S + RT in 23,
      S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active
      treatment was given in one case. After initial treatment there was no tumor in 57
      patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%)
      (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6).
      Five patients died of disease progression and the other 5 of other causes. The 5
      year disease-free survival, disease-specific survival, and overall survival were
      54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival
      were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease
      specific survival were stage, recurrence, and residual tumor (p < 0.01).
      CONCLUSIONS: To our knowledge, this report represents the largest series of MALT
      lymphomas of the salivary glands published to date. This disease may involve all
      salivary glands either initially or subsequently in 30% of patients. Recurrences
      may occur in up to 35% of patients at 5 years; however, survival is not affected.
      Radiotherapy is the only treatment modality that improves disease-free survival.

PMID- 21075561
TI  - High rates of transitions to injecting drug use among Mexican American non
      injecting heroin users in San Antonio, Texas (never and former injectors).
AB  - OBJECTIVE: To assess the incidence and rate of transition to injecting among
      Mexican American noninjecting heroin users. METHODS: In a prospective cohort
      study of street-recruited MA-NIU in San Antonio, Texas, 2002-2005, participants
      were administered structured interviews and tested for Human immunodeficiency
      virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). The analysis
      sample comprised former injection drug users (last injected >6 months ago, n=47)
      and those who had never injected drugs and tested HCV negative (n=219). A
      transition to injecting was defined as the first injection of illicit drugs since
      baseline interview. Transition rates were based on person-years at-risk (PYAR).
      Proportional hazards regression was used to estimate crude and adjusted (for
      significant differences between former and never injectors) hazard ratios and 95%
      confidence intervals of injecting history on transitioning to injecting. RESULTS:
      Sixty-three (24%) participants transitioned to injecting at a rate of 22.3/100
      PYAR (95% CI: 17.2-28.2). Former-injectors were significantly more likely to
      transition than never injectors (43% or 20/47 vs. 20% or 43/219; p<0.001), and
      did so at a faster rate (40.4/100 PYAR, 95% CI: 24.6-60.0 vs. 18.5/100 PYAR, 95%
      CI: 13.4-24.4), with the crude HR=1.931 (95% CI: 1.116, 3.341) and adjusted
      HR=2.263 (95% CI: 1.192-4.294). CONCLUSIONS: The rate of transitioning to
      injecting was high and greater among former injectors. Of particular concern is
      the high rate of injecting initiation among never injectors. Future analyses will
      examine factors associated with injecting initiation, including individual
      susceptibility and behaviors, social networks, and the cultural and drug market
      context.

PMID- 21075562
TI  - Cluster randomised trial of the effectiveness of motivational interviewing for
      universal prevention.
AB  - BACKGROUND: The prevention of initiation of tobacco, alcohol and drug use is a
      major societal challenge, for which the existing research literature is generally
      disappointing. This study aimed to test the effectiveness of adaptation of
      Motivational Interviewing (MI) for universal prevention purposes, i.e. to prevent
      initiation of new substance use among non-users, and to reduce risks among
      existing users. METHODS: Cluster randomised trial with 416 students aged 16-19
      years old recruited in 12 London Further Education colleges without regard to
      substance use status. Individualised MI was compared with standard practice
      classroom-delivered Drug Awareness intervention, both delivered over the course
      of one lesson. Prevalence, initiation and cessation rates for the 3 target
      behaviours of cigarette smoking, alcohol consumption and cannabis use, along with
      reductions in use and harm indicators after both 3 and 12 months were assessed.
      RESULTS: This adaptation of MI was not demonstrated to be effective in either
      intention-to-treat or sub-group analyses for any outcome. Unexpected lower levels
      of cannabis initiation and prevalence were found in the Drug Awareness control
      condition. CONCLUSIONS: This particular adaptation of MI is ineffective as a
      universal drug prevention intervention and does not merit further study.

PMID- 21075563
TI  - Factors associated with missing data in an experience sampling investigation of
      substance use determinants.
AB  - BACKGROUND: The Experience Sampling Method (ESM) collects data repeatedly over
      time, and is therefore prone to missing observations. Little is known about the
      characteristics of the subjects and of the ESM procedure associated with
      unanswered records. Through an ESM investigation of substance use determinants,
      these characteristics were able to be analyzed. METHODS: Participants (n=224)
      were undergraduate university students enrolled for a study of substance use
      factors, providing data through the use of classic questionnaires and through the
      Experience Sampling Method (ESM) using palmtop computers. For the ESM, they were
      signaled five times per day for 7 days (7840 records). Characteristics of the ESM
      procedure and of the participants were analyzed jointly. The probability of an
      unanswered ESM record was analyzed using a random-intercept logistic regression,
      fitting a multivariate mixed-effect model for repeated measurements. RESULTS:
      Factors significantly associated with an unanswered record were: male gender,
      being a Sport Science student, having higher scores of novelty seeking and of
      persistence, and being a poly-substance user. Unanswered records were also more
      frequent in the middle of the week and at the beginning of the day. CONCLUSION:
      Findings are discussed in term of the possible impact of missing observations. In
      particular, the lower compliance of poly-substance users with the ESM protocol
      may curtail the validity of the method, since ESM records are less representative
      of all moments in these persons daily life. Thus, results from ESM studies of
      substance use should be regarded cautiously and complemented with other data
      gathering procedures.

PMID- 21075565
TI  - Development of a predictive model for detection of Mycobacterium avium subsp.
      paratuberculosis in faeces by quantitative real time PCR.
AB  - This study focused on the development of a reliable and cost-efficient DNA
      isolation procedure for the detection of Mycobacterium avium subsp.
      paratuberculosis (MAP) in faeces by previously developed IS900 and F57
      quantitative real time PCR (qPCR) and their comparison with culture. The recovery
      of MAP DNA from the spiking experiments ranged from 29.1 to 102.4% of the input
      amount of MAP with median 37.9%. The limit of detection was determined to be 1.03
      * 10(4) for F57 qPCR and 6.87 * 10(2)MAP cells per gram of faeces for IS900 qPCR,
      respectively. The developed technique for DNA isolation was coupled with IS900
      qPCR and compared to traditional MAP culture using a cohort of 1906 faecal
      samples examined from 12 dairy cattle farms in our laboratory. From those 1906
      original faecal samples, 875 were positive by IS900 qPCR and 169 by culture. None
      of the culture positive samples was negative by IS900 qPCR. This data facilitated
      development of a predictive model capable of estimating the probability of being
      culture positive by estimating the absolute number of MAP per gram of faeces as
      determined IS900 qPCR without performing the culture.

PMID- 21075564
TI  - Assessing white matter integrity as a function of abstinence duration in former
      cocaine-dependent individuals.
AB  - Current cocaine-dependent users show reductions in white matter (WM) integrity,
      especially in cortical regions associated with cognitive control that have been
      associated with inhibitory dysfunction. A key question is whether these white
      matter differences are present following abstinence from drug use. To address
      this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on
      43 cocaine abstinent patients (abstinence duration ranged between five days and
      102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison
      separated the patients into three groups (short-term, mid-term and long-term)
      based upon duration of cocaine abstinence. The 43 cocaine abstinent patients
      showed lower fractional anisotropy (FA) in the left anterior callosal fibers,
      left genu of the corpus callosum, right superior longitudinal fasciculus, right
      callosal fibers and the superior corona radiata bilaterally when compared against
      non-using controls. Higher FA in the cocaine abstinent patients was observed in
      the splenium of the corpus callosum and right superior longitudinal fasciculus.
      Differences between the cocaine abstinent groups were observed bilaterally in the
      inferior longitudinal fasciculus, right anterior thalamic radiation, right
      ventral posterolateral nucleus of the thalamus, left superior corona radiata,
      superior longitudinal fasciculus bilaterally, right cingulum and the WM of the
      right precentral gyrus. The results identified WM differences between cocaine
      abstinent patients and controls as well as distinct differences between abstinent
      subgroups. The findings suggest that specific white matter differences persist
      throughout abstinence while other, spatially distinct, differences discriminate
      as a function of abstinence duration. These differences may, therefore, represent
      brain changes that mark recovery from addiction.

PMID- 21075566
TI  - Functional characterization of polymorphic variants for ovine MT1 melatonin
      receptors: possible implication for seasonal reproduction in sheep.
AB  - In seasonal breeding species, the gene encoding for the melatonin MT(1) receptor
      (oMT(1)) is highly polymorphic and numerous data have reported the existence of
      an association between an allele of the receptor and a marked expression of the
      seasonality of reproduction in ewes. This allele called "m" (previously named "-"
      allele) carries a mutation leading to the absence of a MnlI restriction site as
      opposed to the "M" allele (previously named "+" allele) carrying the MnlI
      restriction site (previously "+" allele). This allows the determination of the
      three genotypes "M/M" (+/+), "M/m" (+/-) and "m/m" (-/-). This mutation is
      conservative and could therefore not be causal. However, it is associated with
      another mutation introducing the change of a valine to an isoleucine in the fifth
      transmembrane domain of the receptor. Homozygous "M/M" and "m/m" animals
      consequently express structurally different receptors respectively named oMT(1)
      Val(220) and oMT(1) Ile(220). The objective of this study was to test whether
      these polymorphic variants are functionally different. To achieve this goal, we
      characterized the binding properties and the transduction pathways associated
      with both variants of the receptors. Using a pharmacological approach, no
      variation in binding parameters between the two receptors when transiently
      expressed in COS-7. In stably transfected HEK293 cells, significant differences
      were detected in the inhibition of cAMP production whereas receptors
      internalization processes were not different. In conclusion, the possibility that
      subtle alterations induced by the non conservative mutation in "m/m" animals
      might modify the perception of the melatoninergic signal is discussed in the
      context of melatonin action.

PMID- 21075567
TI  - The significance of a thickened endometrial echo in asymptomatic postmenopausal
      patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the significance of a
      thickened endometrial echo in an asymptomatic, postmenopausal patient. STUDY
      DESIGN: A retrospective review was conducted of all women who underwent
      transvaginal ultrasonography between January 2003 and August 2008, were found to
      have an endometrial thickness of at least 5mm and were subjected to endometrial
      sampling. RESULTS: Sixty-five postmenopausal women, without vaginal bleeding
      underwent ultrasonographic evaluation with subsequent endometrial sampling. The
      mean endometrial stripe thickness was 9.7 mm (range: 5.4-22). Four (6.2%) cases
      of simple/complex hyperplasia were identified and two (3.1%) cases of atypical
      hyperplasia were diagnosed. Zero (0%) specimens were identified as
      adenocarcinoma. Twenty-eight (43.1%) polyps and eleven (16.9%) leiomyomata were
      identified. CONCLUSION: The use of transvaginal sonography as a screening tool in
      this population is not validated and need not trigger routine evaluation.

PMID- 21075568
TI  - Endocrine disrupters--a threat to women's health?
AB  - Endocrine disruption has been a topic of public concern for many years and its
      study remains high on the scientific agenda. Endocrine disrupters (EDs) are
      compounds which may be of industrial or natural origin and which act to
      dysregulate steroid function and metabolism. As well as their actions on nuclear
      steroid receptors, EDs can inhibit the pathways of steroid synthesis and
      degradation. They not only affect reproductive function but also affect a range
      of tissues which are steroid sensitive such as the central nervous system and
      thyroid. Results from the latest studies suggest that EDs may also affect the
      immune system, glucose homeostasis and can act as epigenetic modulators resulting
      in transgenerational effects. Research in this area has led to the development of
      drugs used in the treatment of several types of hormone-sensitive cancer.
      However, despite many years of effort, the effects on human health of long-term
      environmental exposure to EDs, whether singly or as mixtures, remain unknown.

PMID- 21075570
TI  - Detecting buried metallic weapons in a controlled setting using a conductivity
      meter.
AB  - Forensic personnel may face a daunting task when searching for buried weapons at
      crime scenes or potential disposal sites. In particular, it is common to search
      for a small firearm that was discarded or buried by a perpetrator. When
      performing forensic searches, it is recommended to first use non-invasive methods
      such as geophysical instruments to minimize damage to evidence and to the crime
      scene. Geophysical tools are used to pinpoint small areas of interest across a
      scene for invasive testing, rather than digging large areas throughout the site.
      Prior to this project, there was no published research that tested the utility of
      the conductivity meter to search for metallic weapons such as firearms and blunt
      and sharp edged weapons. A sample comprised of 32 metallic weapons including
      firearms, blunt and sharp edged weapons, and scrap metals was buried in a
      controlled setting to test the applicability of a conductivity meter for forensic
      searches. Weapons were tested at multiple depths and after data collection was
      performed for one depth, the weapons were reburied 5 cm deeper until they were no
      longer detected. Variables such as weapon size, burial depth, transect interval
      spacing (25 and 50 cm), and metallic composition were tested. All of the
      controlled variables influenced maximum depth of detection. For example, size was
      a factor as larger weapons were detected at deeper depths compared to smaller
      weapons. Metal composition affected maximum depth of detection as the
      conductivity meter detected items comprised of ferrous metals at deeper depths
      than non-ferrous metals. Searches for large buried items may incorporate a
      transect interval spacing of 50 cm but small weapons may be undetected between
      transects and therefore a transect interval spacing of 25 cm is recommended.
      Overall, the conductivity meter is a geophysical tool to consider when searching
      for larger-sized metallic weapons or to use in conjunction with an all-metal
      detector, particularly when searching for buried metallic evidence in obstructed
      areas.

PMID- 21075569
TI  - Aging with a disability: a systematic review of cardiovascular disease and
      osteoporosis among women aging with a physical disability.
AB  - Compared to men, women live longer but experience greater morbidity as they age.
      However, little is known about the rapidly growing population of women aging with
      disability. Women aging with disabilities may encounter barriers that increase
      risk of morbidity, including lack of access to medical care or inadequate
      assistance, equipment, or services. To evaluate risks of morbidity in this group,
      we conducted a systematic review focused on two important and prevalent
      conditions: cardiovascular disease (CVD) and osteoporosis. MEDLINE was searched
      for reports published between January 1, 1990 and August 6, 2010 and additional
      studies were identified through searches of bibliographies. 9156 abstracts and 93
      articles were reviewed to identify empirical studies of women with physical
      disability who were 45 years or older and that reported CVD or osteoporosis as an
      outcome and not a cause of the disability. Articles meeting inclusion criteria
      were then critically appraised to exclude poor quality studies. In seven articles
      that evaluated CVD outcomes, we found limited evidence to support an increased
      risk of prevalence of CVD or risk factors for CVD in women aging with physical
      disabilities compared to non-disabled control populations. The literature is
      limited by small sample sizes that reduced statistical power to detect true
      differences. No articles meeting inclusion criteria were identified to evaluate
      osteoporosis risk in this group. This review is limited by the narrow focus on
      physical disabilities and two health outcomes. Additional high quality empirical
      research is necessary to understand the risks to health of women aging with
      disabilities.

PMID- 21075571
TI  - Multi-disciplinary forensic medical efforts of the disaster victim identification
      (DVI) response to intense bushfires in February, 2009 in Victoria, Australia.
      Preface.

PMID- 21075572
TI  - New onset refractory convulsive status epilepticus associated with serum neuropil
      auto-antibodies in a school aged child.
AB  - We report a case of a child that suffered from a severe new onset status
      epilepticus a few days after a common viral infection. Despite extensive
      screening, no bacterial, viral or fungal infection could be found. Using
      immunohistochemical analysis, we found neuronal auto-antibodies directed against
      the neuropil, in blood and CSF, associated with CSF oligoclonal banding. Status
      epilepticus was highly refractory to antiepileptic drugs, but improved few days
      after Intra-Venous Immunoglobulin Injection (IVIG). The patient developed ongoing
      temporal lobe epilepsy that was still associated with neuropil auto-antibodies.
      Therefore, screening for antineuronal antibodies should be helpful to
      characterize and maybe to handle new onset status epilepticus without any obvious
      aetiology. Further studies should establish the link between epilepsy and such
      auto-antibodies.

PMID- 21075573
TI  - Source localization in magnetoencephalography to identify epileptogenic foci.
AB  - RATIONALE: Magnetoencephalography (MEG) is useful to localize epileptic foci in
      epilepsy as MEG has higher spatio-temporal resolution than conventional
      diagnostic imaging studies; positron emission computed tomography, single photon
      emission computed tomography and magnetic resonance imaging (MRI). METHODS: We
      use 204-channel helmet-shaped MEG with a sampling rate of 600 Hz. A single dipole
      method calculates equivalent current dipoles to localize epileptic sources. The
      equivalent current dipoles are superimposed onto MRI as magnetic source imaging
      (MSI). Ictal MEG data are analyzed using time-frequency analysis. The power
      spectrum density is calculated using short-time Fourier transform and
      superimposed onto MRI results. RESULTS: Clustered equivalent current dipoles
      represent epileptogenic zones in patients with localization-related epilepsy. The
      surgical plan is reliably developed from source localizations of dipoles and
      power spectrum of interictal spike discharges, and ictal frequency. CONCLUSION:
      MEG is indispensable in diagnosis and surgical resection for epilepsy to
      accurately localize the epileptogenic zone.

PMID- 21075574
TI  - Feasibility and safety of granulocytapheresis in Crohn's disease: a prospective
      cohort study.
AB  - BACKGROUND AND OBJECTIVE: This study evaluated the feasibility and safety of
      granulocytapheresis (GCAP) in inducing and maintaining remission in refractory
      Crohn's disease. The relationship between the clinical outcomes and the location
      (ileal or ileocolonic) of disease was also assessed. PATIENTS: We evaluated 16
      patients with ileal location (group A), 14 with ileocolonic location (group B).
      The patients underwent five sessions (1 session/wk) of GCAP (Adacolumn(TM)). CDAI
      was measured at the end of the GCAP, at 6, 9 and 12 months. RESULTS AND
      CONCLUSIONS: No major complications were observed. At the end of GCAP, 19 (63.3%)
      patients showed a clinical remission: 10 (62.5%) in group A versus 9 (64.2%) in
      group B. At 6 months, 16 (53.3%) of the cases had maintained remission: 9 (56.2%)
      in group A versus 7 (50.0%) in group B. At 9 months, 13 (43.3%) patients had
      maintained remission: 7 (43.7%) in group A versus 6 (42.8%) in group B. At 12
      months, 12 (40%) patients were still in clinical remission: 7 (43.7%) in group A
      versus 5 (35.7%) in group B. Risk of relapse was not related to disease location.
      The procedure was well tolerated and feasible in an important percentage of
      Crohn's disease patients.

PMID- 21075575
TI  - Development and validation of indirect RP-HPLC method for enantiomeric purity
      determination of D-cycloserine drug substance.
AB  - A new chiral purity method was developed for D-cycloserine (D-cys) by reverse
      phase HPLC and validated. Chiral derivatizing reagents, viz., o-phthalaldehyde
      and N-acetyl-L-cysteine were utilized in this method. The resultant diastereomers
      were resolved using Zorbax SB Phenyl HPLC column under isocratic elution. A
      mobile phase of 95:05 (v/v), 20mM Na(2)HPO(4) (pH 7), and acetonitrile,
      respectively, was used with the flow rate of 1.0 mL/min and UV detection at 335
      nm. The method development with different chiral stationary phases and chiral
      derivatization reagents were also investigated. The stability of diastereomer
      derivative and influence of organic modifier and pH of the mobile phase were
      studied and optimized. The stability-indicating capability of the method was
      established by performing stress studies under acidic, basic, oxidation, light,
      humidity and thermal conditions. The detection and quantitation limit of L
      cycloserine (L-cys) were 0.015 and 0.05% (w/w), respectively. A linear range from
      0.05 to 0.30% (w/w) was obtained with the coefficient of determination (r(2))
      0.998. The recovery obtained for L-cys was between 92.9 and 100.2%. This method
      was applied successfully in pharmaceutical analysis to determine the content of L
      cys in D-cys bulk drug.

PMID- 21075576
TI  - Development of a stability-indicating UPLC method for determining olanzapine and
      its associated degradation products present in active pharmaceutical ingredients
      and pharmaceutical dosage forms.
AB  - A simple, sensitive and reproducible ultra performance liquid chromatography
      (UPLC) coupled with a photodiode array detector method was developed for the
      quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage
      forms. The method is applicable to the quantification of related substances and
      assays of drug substances. Chromatographic separation was achieved on Acquity
      UPLC BEH 100-mm, 2.1-mm, and 1.7-MUm C-18 columns, and the gradient eluted within
      a short runtime, i.e., within 10.0 min. The eluted compounds were monitored at
      250 nm, the flow rate was 0.3 mL/min, and the column oven temperature was
      maintained at 27 degrees C. The resolution of OLN and eight (potential, bi
      products and degradation) impurities was greater than 2.0 for all pairs of
      components. The high correlation coefficient (r(2)>0.9991) values indicated clear
      correlations between the investigated compound concentrations and their peak
      areas within the test ranges. The repeatability and intermediate precision,
      expressed by the RSD, were less than 2.4%. The accuracy and validity of the
      method were further ascertained by performing recovery studies via a spike
      method. The accuracy of the method expressed as relative error was satisfactory.
      No interference was observed from concomitant substances normally added to the
      tablets. The drug was subjected to the International Conference on Harmonization
      (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions.
      The performance of the method was validated according to the present ICH
      guidelines for specificity, limit of detection, limit of quantification,
      linearity, accuracy, precision, ruggedness and robustness.

PMID- 21075577
TI  - Simultaneous qualification and quantification of baccharane glycosides in
      Impatientis Semen by HPLC-ESI-MSD and HPLC-ELSD.
AB  - This study presents a high performance liquid chromatography (HPLC) with
      electrospray ionization mass spectrometric detection (ESI-MSD) and evaporative
      light scattering detection (ELSD) method for the simultaneous qualification and
      quantification of eight major baccharane glycosides, namely hosenlosides A, B, C,
      F, G, K, L, and M in Impatientis Semen, a Chinese herbal medicine derived from
      the seeds of Impatiens balsamina L. In order to achieve optimum performance,
      several extraction parameters (including extraction solvent, extraction mode,
      extraction time) were optimized. The baccharane glycosides were separated on a
      Shim-pack CLC-ODS column with gradient elution of water and methanol. Temperature
      for the ELSD drift tube was set at 98 degrees C and the nitrogen flow rate was
      2.7l/min. The unambiguous identities of the analytes were realized by comparing
      retention times and mass data with those of reference compounds. The developed
      method was fully validated in terms of linearity, sensitivity, precision,
      repeatability, recovery as well as robustness, and subsequently applied to
      evaluate the quality of 14 batches of Impatientis Semen commercial samples from
      different collections.

PMID- 21075578
TI  - Does adding low doses of oral naltrexone to morphine alter the subsequent opioid
      requirements and side effects in trauma patients?
AB  - OBJECTIVE: The present study aims to assess the influence of ultra-low doses of
      opioid antagonists on the analgesic properties of opioids and their side effects.
      METHODS: In the present randomized, double-blind controlled trial, the influence
      of the combination of ultra-low-dose naltrexone and morphine on the total opioid
      requirement and the frequency of the subsequent side effects was compared with
      that of morphine alone (added with placebo) in patients with trauma in the upper
      or lower extremities. RESULTS: Although the morphine and naltrexone group
      required 0.04 mg more opioids during the study period, there was no significant
      difference between the opioid requirements of the 2 groups. Nausea was less
      frequently reported in patients receiving morphine and naltrexone. CONCLUSION:
      The combination of ultra-low-dose naltrexone and morphine in extremity trauma
      does not affect the opioid requirements; it, however, lowers the risk of nausea.

PMID- 21075579
TI  - Life-threatening hyperkalemia from nutritional supplements: uncommon or
      undiagnosed?
AB  - Potassium chloride and other potassium compounds are used by the general public
      as salt substitutes, muscle-building supplements, and panacea. Severe
      hyperkalemia from oral potassium is extremely rare if kidney function is normal
      because of potassium adaptation. The oral potassium dose has to be large enough
      to overcome the normal renal excretory mechanisms to cause severe hyperkalemia.
      This occurs most commonly in patients with renal impairment or those who take
      potassium-sparing diuretics, angiotensin receptor blockers, or angiotensin
      converting enzyme inhibitors. We present two unique cases of near-fatal
      hyperkalemia from nutritional supplements containing potassium. The first case
      was due to salt-substitute intake, whereas the second case was from a muscle
      building supplement. Both patients suffered cardiac arrest, but were successfully
      resuscitated and survived. The acuity of intake and excessive quantity
      overwhelmed the kidneys' ability for adaptation. Potassium toxicity affects
      multiple organ systems and manifests in characteristic, acute cardiovascular
      changes with electrocardiographic abnormalities. Neuromuscular manifestations
      include general muscular weakness and ascending paralysis may occur, whereas
      gastrointestinal symptoms manifest as nausea, vomiting, paralytic ileus, and
      local mucosal necrosis that may lead to perforation. Once an urgent situation has
      been handled with intravenous push of a 10% calcium salt, short-term measures
      should be started with agents that cause a transcellular shift of potassium,
      namely, insulin with glucose, beta2-agonist, and NaHCO(3). Patients are unaware
      of these potentially serious adverse effects, and there are inadequate consumer
      warnings. Clinicians should be vigilant in monitoring potassium intake from over
      the-counter supplements.

PMID- 21075580
TI  - Cord sign facilitates the early diagnosis of deep cerebral vein thrombosis.
AB  - The diagnosis of deep cerebral vein thrombosis is challenging. Brain computed
      tomography only has limited information. Brain magnetic resonance imaging and
      venography can make the diagnosis by revealing venous thrombosis. In this case
      report, we will introduce the unique image findings in brain computed tomography,
      which may facilitate early diagnosis and result in a better prognosis.

PMID- 21075581
TI  - Isoproterenol as an adjunct for treatment of idiopathic ventricular fibrillation
      storm in a pregnant woman.
AB  - Idiopathic ventricular fibrillation is a rare entity seen in a very small subset
      of patients presenting to the emergency department. Management of ventricular
      arrhythmias in pregnant women is similar to that in nonpregnant women, but
      special consideration is given to avoid adverse fetal effects when selecting
      antiarrhythmic agents. Electrical defibrillation is the intervention of choice in
      both pregnant and nonpregnant patients with ventricular fibrillation of all
      etiologies. This was not associated with any significant adverse effects for
      mother or fetus. Although lidocaine and sotalol are Food and Drug Administration
      category B antiarrhythmics used in pregnancy, Food and Drug Administration
      category C antiarrhythmics such as beta-blockers and category D drugs such as
      amiodarone can be used as pharmacologic adjuncts to facilitate termination of
      recurrent ventricular fibrillation where other agents have failed. Isoproterenol
      has been used to terminate recurrent ventricular fibrillation in patients with
      Brugada syndrome and torsades de pointes resistant to magnesium therapy. This
      case report describes a previously healthy 32-year-old pregnant woman with
      recurrent idiopathic ventricular fibrillation that failed to respond to standard
      therapy including electrical defibrillation, intravenous lidocaine, metoprolol,
      and amiodarone but eventually terminated with isoproterenol infusion.

PMID- 21075582
TI  - A physician's personal experience as a neck breather needing emergency care.

PMID- 21075583
TI  - Ciprofloxacin-induced torsade de pointes.
AB  - A 65-year-old man with recently diagnosed urinary tract infection treated with
      ciprofloxacin (Cipro) presented to our institution with recurrent seizure-like
      activity. His rhythm revealed torsade de pointes, which required defibrillation.
      Subsequent electrocardiogram revealed severely prolonged QT interval, which near
      completely resolved 7 days later off Cipro. This case highlights a rare but
      potentially fatal side effect of quinolone antibiotics, especially in combination
      with other QT-prolonging medications. Review of the literature with regard to
      prevalence, mechanism, and assessment and treatment of this potentially fatal
      incidence is provided.

PMID- 21075584
TI  - Post-computed tomography of the kidney, ureter, and bladder diagnosis of urinary
      extravasation.

PMID- 21075585
TI  - Hyperthermia occurred after hyperbaric oxygen therapy for carbon monoxide
      poisoning.

PMID- 21075586
TI  - High rates of quinolone resistance among urinary tract infections in the ED.
AB  - OBJECTIVES: The objectives of this study are to examine antibiotic resistance
      rates and to determine appropriate empiric oral antibiotic for patients with
      urinary tract infections (UTIs) evaluated and discharged from the ED. METHODS: A
      retrospective, single-institution chart review study from August 2008 to March
      2009 was conducted. Adult patients seen in the ED with UTI were identified for
      study inclusion from review of microbiology records. Hospitalized or asymptomatic
      bacteriuria cases were excluded. Health care-associated (HA)-UTI was defined as
      UTI with indwelling urinary catheters, health care exposure, or urologic
      procedures within 3 months. Prevalence of causative bacteria, antibiotic
      resistance rates, and risk factors for quinolone resistance were determined.
      RESULTS: There were 337 eligible patients with 83% women. The most common
      uropathogens among 357 bacterial isolates were Escherichia coli (71%) and
      Klebsiella spp. (9%). Overall levofloxacin resistance rate was 17%. Resistance
      rates for HA-UTIs were significantly greater than those for community-associated
      UTI: levofloxacin, 38% vs 10%; trimethoprim-sulfamethoxazole, 26% vs 17%;
      amoxicillin, 53% vs 45%; and amoxicillin-clavulanate, 16% vs 6%. Nitrofurantoin
      resistance rates were similar (9%). Independent risk factors for levofloxacin
      resistance were long-term medical conditions (adjusted odds ratio [aOR], 4.23; P
      = .001), HA-UTI (aOR, 2.56; P = .006), and prior quinolone use within 1 week
      (aOR, 14.90; P = .02) and within 1 to 4 weeks (aOR, 4.62; P = .04). CONCLUSIONS:
      We report high rates of quinolone resistance in ED patients with UTIs at our
      institution. For patients with risk factors for quinolone resistance, empiric
      therapy with cephalosporins or nitrofurantoin may be preferred. Urine culture and
      susceptibility testing should be performed to guide definitive therapy for HA
      UTIs.

PMID- 21075587
TI  - Biochemical issues in emergency medicine: diagnostic and therapeutic
      considerations of selected toxic presentations.
AB  - Understanding biochemical concepts can assist in the diagnosis and treatment of
      certain presentations in the emergency department. Knowledge of the biochemistry
      responsible for certain presentations in the emergency department as well as
      behind various therapies also provides physicians better insight into the use of
      specific treatments. This review will focus on the biochemistry of numerous
      clinical syndromes, including methemoglobinemia, various poisoning presentations,
      including cyanide, methanol, and ethylene glycol--with an emphasis on the
      diagnostic and management considerations in these presentations.

PMID- 21075588
TI  - Atypical presentation of fatal meningococcemia: peritonitis and paradoxical
      centrifugal purpura fulminans of late onset.

PMID- 21075589
TI  - Counselling in infertility: individual, couple and group interventions.
AB  - OBJECTIVE: Infertility is considered a biopsychosocial crisis and infertility
      counselling is recommended as an integral part of a multidisciplinary approach.
      This article will outline the theoretical background and describe common
      interventions used in infertility counselling for individuals, couples and in a
      group setting. METHODS: This article summarizes the proceedings of the first
      campus workshop of the Special interest group of Psychology and Counselling of
      the European Society for Human Reproduction and Embryology (ESHRE). RESULTS:
      Infertility counselling offers the opportunity to explore, discover and clarify
      ways of living more satisfyingly and resourcefully when fertility impairments
      have been diagnosed. The Heidelberg Fertility Consultation Service is presented
      as a framework for individual and couples counselling and highlights important
      issues in counselling patients. For group work a number of steps to set up a
      group within an infertility framework are discussed. CONCLUSION: In recent years,
      infertility counselling has become a specialist form of counselling requiring
      professional expertise and qualification. Key issues and common interventions are
      presented to raise awareness for the specific counselling needs of individuals
      and couples experiencing infertility and undergoing medical treatment. PRACTICE
      IMPLICATIONS: Mental health professionals new to the field of reproductive
      technologies as well as those in other areas of mental health counselling clients
      with fertility disorders can benefit from the topics addressed.

PMID- 21075590
TI  - Assessment of physician competency in patient education: reliability and validity
      of a model-based instrument.
AB  - OBJECTIVE: Establish the inter-rater reliability and the concept, convergent and
      construct validity of an instrument for assessing the competency of physicians in
      patient education. METHODS: Three raters assessed the quality of patient
      education in 30 outpatient consultations with the CELI instrument. This
      instrument is based on a goal-directed model of patient education and assesses
      distinctive skills for patient education categorized in four subcompetencies. The
      inter-rater reliability was calculated. The concept validity was explored by
      factor analysis. The convergent validity was established by a comparison with two
      measures of patient-centred behaviour. The construct validity was explored by
      relating the subcompetencies with physician gender and patient satisfaction.
      RESULTS: The inter-rater reliability for the subcompetencies varied between 0.65
      and 0.91. The factor analysis distinguished the four subcompetencies. All
      subcompetencies correlated with the measures of patient-centred behaviour. Female
      physicians performed better than male physicians on three subcompetencies.
      Positive correlations were found for three subcompetencies and patient
      satisfaction. CONCLUSION: The CELI instrument appears to be a reliable and valid
      instrument. However, further research is needed to establish the generalizability
      and construct validity. PRACTICE IMPLICATION: The CELI instrument is a useful
      tool for assessment and feedback in medical education since it assesses the
      performance of distinctive skills.

PMID- 21075591
TI  - [Giant biloma in the course of choledocholithiasis].

PMID- 21075592
TI  - The Multi-Dimensional Blood/Injury Phobia Inventory: its psychometric properties
      and relationship with disgust propensity and disgust sensitivity.
AB  - The Multi-Dimensional Blood Phobia Inventory (MBPI; Wenzel & Holt, 2003) is the
      only instrument available that assesses both disgust and anxiety for blood-phobic
      stimuli. As inflated levels of disgust propensity (i.e., tendency to experience
      disgust more readily) are often observed in blood phobia, the MBPI appears a
      promising instrument for disgust research. First, we examined its psychometric
      properties. Next, it was examined whether disgust sensitivity (i.e., considering
      experiencing disgust as something horrid) had added predictive value compared to
      disgust propensity in blood phobia. Therefore, students and university employees
      (N = 616) completed the MBPI, indices on blood phobia, disgust propensity and
      sensitivity. The MBPI proved to be reliable and valid. Further, it correlated
      moderately to high with disgust propensity and sensitivity. Additionally, disgust
      propensity and sensitivity were both significant predictors for blood phobia. In
      conclusion, the MBPI appears a valuable addition to the currently available
      arsenal of indices to investigate blood phobia.

PMID- 21075593
TI  - Differential activity of subgenual cingulate and brainstem in panic disorder and
      PTSD.
AB  - Most functional neuroimaging studies of panic disorder (PD) have focused on the
      resting state, and have explored PD in relation to healthy controls rather than
      in relation to other anxiety disorders. Here, PD patients, posttraumatic stress
      disorder (PTSD) patients, and healthy control subjects were studied with
      functional magnetic resonance imaging utilizing an instructed fear conditioning
      paradigm incorporating both Threat and Safe conditions. Relative to PTSD and
      control subjects, PD patients demonstrated significantly less activation to the
      Threat condition and increased activity to the Safe condition in the subgenual
      cingulate, ventral striatum and extended amygdala, as well as in midbrain
      periaquaeductal grey, suggesting abnormal reactivity in this key region for fear
      expression. PTSD subjects failed to show the temporal pattern of activity
      decrease found in control subjects.

PMID- 21075594
TI  - Use of the Gait Deviation Index for the assessment of gastrocnemius fascia
      lengthening in children with Cerebral Palsy.
AB  - Gait analysis (GA) is widely used for clinical evaluations and it is recognized
      as a central element in the quantitative evaluation of gait, in the planning of
      treatments and in the pre vs. post intervention evaluations in children with
      Cerebral Palsy (CP). Otherwise, GA produces a large volume of data and there is
      the clinical need to provide also a quantitative measure of the patient's overall
      gait. Starting from this aim some global indexes were proposed by literature as a
      summary measure of the patient's gait, such as the Gait Deviation Index (GDI).
      While validity of the GDI is demonstrated for the evaluation of the functional
      limitation of CP patients, no studies have evaluated with the GDI the pre vs.
      post surgery gait condition in children with CP. The aim of our study was
      therefore to investigate the effectiveness of the GDI in the quantification of
      gait changes occurring after surgical intervention (gastrocnemius fascia
      lengthening for the correction of equinus foot deformity) in patients with CP. 19
      children with CP were evaluated pre-operatively (PRE session) and about 1 year
      (POST: mean 13.1 +/- 5.1 months) after gastrocnemius fascia lengthening using 3D
      GA. From GA data the GDI was computed. The results evidenced that the GDI value
      in the PRE session was 70.4 +/- 14.8, showing a moderate global disturbance of
      the gait patterns of the patients. After the surgical treatment a significant
      improvement of the GDI mean value was found (82.9 + 7.4; p < 0.05; CG >= 100)
      with an improvement of 18% respect to the PRE session. A strong correlation (rho
      = 0.83; p<0.05) existed between the GDI value in the PRE session and the
      percentage of improvement. Our results demonstrated that GDI seems to be an
      appropriate outcome measure for the evaluation of the effects of surgical
      treatment in CP.

PMID- 21075595
TI  - The development of a diagnostic instrument to measure social information
      processing in children with mild to borderline intellectual disabilities.
AB  - A growing interest exists in the measuring of social adaptive functioning in
      children with mild to borderline intellectual disabilities (MBID), but valid
      instruments to measure this construct are lacking. The aim of the present study
      was to develop such an instrument and to examine it on its discriminate validity.
      In 141 children aged 8-12 years a new test battery was examined in four groups
      either with MBID, behaviour problems or both, and typically developing peers. The
      results show that children with either MBID or behaviour problems or both show
      more hostile intent attributions, set more internal revenge goals, generate more
      aggressive and fewer assertive responses, feel more confident in inadequate
      responses en select fewer assertive responses, than their typically developing
      peers. Children with MBID are characterized by relying on earlier experiences in
      encoding information, a small response repertoire, positive evaluation of
      submissive but not assertive responses, and the selection of aggressive
      responses. In addition, they have more problems with perspective taking, problem
      recognition, interpretation in general, inhibition, working memory, and emotion
      recognition, than their typically developing peers. Further, children with MBID
      and behaviour problems have more difficulties in social information processing
      when the information in social situations is more complex. It is concluded that
      the tasks of the test battery can discriminate between groups, and after further
      development of the material, can be used to obtain information on the
      competencies and disabilities in social information processing and social
      cognitive skills, in order to be able to offer adequate treatment to these
      children.

PMID- 21075596
TI  - Inclusion of methodological filters in searches for diagnostic test accuracy
      studies misses relevant studies.
AB  - OBJECTIVE: To compare the performance of MEDLINE searches using index test(s) and
      target condition (subject searches) with the same searches combined with
      methodological filters for test accuracy studies. STUDY DESIGN AND SETTING: We
      derived a reference set of 506 test accuracy studies indexed on MEDLINE from
      seven systematic reviews that conducted extensive searches. We compared the
      performance of "subject" with "filtered" searches (same searches combined with
      each of 22 filters). Outcome measures were number of reference set records
      missed, sensitivity, number needed to read (NNR), and precision (Number of
      reference set studies identified for every 100 records screened). RESULTS:
      Subject searches missed 47 of the 506 reference studies; filtered searches missed
      an additional 21 to 241 studies. Sensitivity was 91% for subject searches and
      ranged from 43% to 87% for filtered searches. The NNR was 56 (precision 2%) for
      subject searches and ranged from 7 to 51 (precision 2-15%) for filtered searches.
      CONCLUSIONS: Filtered searches miss additional studies compared with searches
      based on index test and target condition. None of the existing filters provided
      reductions in the NNR for acceptable sensitivity; currently available
      methodological filters should not be used to identify studies for inclusion in
      test accuracy reviews.

PMID- 21075599
TI  - A combined superficial inferior epigastric artery flap and vascularized iliac
      crest flap in the reconstruction of extended composite defects of the posterior
      mandible and adjacent soft tissue: first clinical results.
AB  - The technique of posterior facial reconstruction using a combination of a
      superficial inferior epigastric artery (SIEA) flap and a microvascular iliac
      crest flap (deep circumflex iliac artery (DCIA) flap) is described. 12 cases are
      reported. The patients had unilateral squamous cell carcinoma of the posterior
      mandible affecting parts of the soft palate and tonsil region or the posterior
      cheek. In all patients unilateral neck dissection, resection of the posterior and
      lateral mandible, was performed. Reconstruction was carried out during primary
      surgical therapy, followed by postoperative radiotherapy. A flap combination of a
      SIEA and a DCIA flap was used. There were no problems with pedicle length or
      anastomoses. There was no flap loss or severe postoperative complications. All
      patients had good aesthetic and functional results. One patient had distant
      metastases 2 years postoperatively. All other patients were free of tumour
      relapse or metastases within 12-58 months of follow up. The SIEA flap and
      vascularized iliac bone flap combination is useful in reconstructing the
      posterior face. The iliac bone flap is well suited for posterior mandible
      reconstruction and the SIEA flap for reconstruction of the soft palate, lateral
      pharyngeal wall and cheek. Both flaps are harvested from the same donor site.

PMID- 21075598
TI  - Autoimmunity in common variable immunodeficiency: correlation with lymphocyte
      phenotype in the French DEFI study.
AB  - Common variable immunodeficiency (CVID) is the most frequent clinically expressed
      primary immunodeficiency in adults and is characterized by primary defective
      immunoglobulin production. Besides recurrent infectious manifestations, up to 20%
      of CVID patients develop autoimmune complications. In this study, we took
      advantages of the French DEFI database to investigate possible correlations
      between peripheral lymphocyte subpopulations and autoimmune clinical expression
      in CVID adult patients. In order to analyse homogeneous populations of patients
      with precise clinical phenotypes, we first focused on patients with autoimmune
      cytopenia because they represent prototypic autoantibody mediated diseases. In a
      secondary analysis, we have tested our conclusions including all "autoimmune"
      CVID patients. We describe one of the largest European studies with 311 CVID
      patients, including 55 patients with autoimmune cytopenia and 61 patients with
      clinical or serologic autoimmune expression, excluding autoimmune cytopenia. We
      clarify previous reports and we confirm a very significant correlation between an
      increased proportion of CD21(low) B cells and CVID associated autoimmune
      cytopenia, but independently of the presence of other autoimmune disorders or of
      splenomegaly. Moreover, in CVID associated autoimmune cytopenia, T cells display
      an activated phenotype with an increase of HLA-DR and CD95 expression and a
      decrease in the naive T cell numbers. Patients with other autoimmune
      manifestations do not harbour this "T and B cells phenotypic picture". In view of
      recent findings on CD21(low) B cells in CVID and RA, we suggest that both a
      restricted subset of B cells and a T cell help are required for a breakdown of B
      cell tolerance against membrane auto antigens in CVID.

PMID- 21075597
TI  - Th17 cells can provide B cell help in autoantibody induced arthritis.
AB  - K/BxN mice develop a spontaneous destructive arthritis driven by T cell dependent
      anti-glucose-6-phosphate isomerase (GPI) antibody production. In this study, a
      modified version of the K/BxN model, the KRN-cell transfer model (KRN-CTM), was
      established to determine the contribution of Th17 cells in the development of
      chronic arthritis. The transfer of naive KRN T cells into B6.TCR.Calpha(-/-)H
      2(b/g7) T cell deficient mice induced arthritis by day 10 of transfer. Arthritis
      progressively developed for a period of up to 14 days following T cell transfer,
      thereafter the disease severity declined, but did not resolve. Both IL-17A and
      IFNgamma were detected in the recovered T cells from the popliteal lymph nodes
      and ankles. The transfer of KRN Th17 polarized KRN CD4(+) T cells expressing IL
      17A and IFNgamma induced arthritis in all B6.TCR.Calpha(-/-)H-2(b/g7) mice
      however the transfer of Th1 polarized KRN CD4(+) T cells expressing IFNgamma
      alone induced disease in only 2/3 of the mice and disease induction was delayed
      compared to Th17 transfers. Th17 polarized KRN/T-bet(-/-) cells induced arthritis
      in all mice and surprisingly, IFNgamma was produced demonstrating that T-bet
      expression is not critical for arthritis induction, regardless of the cytokine
      expression. Neutralization of IFNgamma in KRN Th17 transfers resulted in earlier
      onset of disease while the neutralization of IL-17A delayed disease development.
      Consistent with K/BxN mice, naive KRN T cell transfers and Th17 polarized KRN/T
      bet(-/-) transfers induced anti-GPI IgG(1) dominant responses while KRN Th17
      cells induced high levels of IgG(2b). These data demonstrate that Th17 cells can
      participate in the production of autoantibodies that can induce arthritis.

PMID- 21075600
TI  - Characteristics of the MATRICS Consensus Cognitive Battery in a 29-site
      antipsychotic schizophrenia clinical trial.
AB  - OBJECTIVE: The Measurement and Treatment Research to Improve Cognition in
      Schizophrenia (MATRICS) Project produced a battery of tests, the MATRICS
      Consensus Cognitive Battery (MCCB), designed to assess cognitive treatment
      effects in clinical trials of patients with schizophrenia. In validation studies,
      the MCCB demonstrated excellent reliability, minimal practice effects and
      significant correlations with measures of functional capacity. This study
      addresses whether the MCCB demonstrates these favorable characteristics when
      administered in the context of the type of large multi-site industry trial for
      which it was designed. METHODS: In a clinical trial comparing risperidone and
      lurasidone, 323 clinically-stable outpatients with schizophrenia at 29 sites were
      assessed with MCCB at screening and a median of 15days later at baseline. A
      measure of functional capacity, the UCSD Performance-based Skills Assessment
      Brief (UPSA-B) was administered at baseline. RESULTS: All 323 (100%) patients had
      sufficient data for computing a composite score according to the MCCB criteria.
      The test-retest reliability of the MCCB composite score was excellent (ICC=0.88).
      The severity of cognitive impairment was T=24.7 (SD=12.1) at screening and T=26.7
      (SD=12.4) at baseline. The MCCB composite score demonstrated a large correlation
      with the UPSA-B composite score (r=.60, df=304, p<.001). The practice effect on
      the composite score was small (z=0.18). DISCUSSION: In the context of a 29-site
      antipsychotic trial in stable outpatients with schizophrenia, the MCCB is
      sensitive to cognitive deficits in all domains, demonstrates excellent test
      retest reliability and small practice effects, and is strongly correlated with a
      leading measure of functional capacity.

PMID- 21075601
TI  - Spatial working memory impairments induced by cigarette smoking abstinence are
      correlated with plasma nicotine levels in schizophrenia.

PMID- 21075602
TI  - Antimicrobial characterisation of solithromycin (CEM-101), a novel
      fluoroketolide: activity against staphylococci and enterococci.
AB  - Solithromycin (CEM-101) is a novel fluoroketolide with high potency against Gram
      positive and Gram-negative bacteria commonly associated with community-acquired
      respiratory tract infections and skin and skin-structure infections. In this
      study, solithromycin and comparator antimicrobials were tested against a
      contemporary collection of Staphylococcus aureus, coagulase-negative
      staphylococci, Enterococcus faecalis, Enterococcus faecium and other Enterococcus
      spp. collected in the SENTRY Antimicrobial Surveillance Program. Solithromycin
      was active against S. aureus [minimum inhibitory concentration for 50% of the
      organisms (MIC(50))=0.12 MUg/mL] and was two-fold more active than telithromycin
      (MIC(50)=0.25 MUg/mL). Solithromycin was more potent against methicillin
      (oxacillin)-susceptible S. aureus [MIC(50)=0.06 MUg/mL and MIC for 90% of the
      organisms (MIC(90))=0.12 MUg/mL) compared with methicillin (oxacillin)-resistant
      S. aureus (MIC(50)=0.12 MUg/mL and MIC(90)>16 MUg/mL). Solithromycin activity was
      reduced amongst heterogeneous vancomycin-intermediate S. aureus and vancomycin
      resistant S. aureus (MIC(50)>16 MUg/mL). Against strains with defined
      susceptibilities to erythromycin, clindamycin and telithromycin, solithromycin
      showed potent inhibition against all combinations (MIC(50)=0.06 MUg/mL) except
      those with non-susceptibility to telithromycin (>2 MUg/mL) (MIC(50)>16 MUg/mL).
      The solithromycin MIC(50) for E. faecium (1 MUg/mL) was four-fold higher than the
      MIC(50) for E. faecalis (0.25 MUg/mL). In summary, solithromycin demonstrated
      high potency against many Staphylococcus and Enterococcus spp. isolated from
      contemporary infections worldwide.

PMID- 21075603
TI  - Linezolid-related immune-mediated severe thrombocytopenia.

PMID- 21075604
TI  - Inhibition of efflux pumps in methicillin-resistant Staphylococcus aureus and
      Enterococcus faecalis resistant strains by triterpenoids from Momordica
      balsamina.
AB  - Six cucurbitane-type triterpenoids (1-6) isolated from the aerial parts of
      Momordica balsamina were evaluated for their ability to inhibit the activity of
      bacterial efflux pumps of methicillin-resistant Staphylococcus aureus (MRSA)
      COL(OXA), Enterococcus faecalis ATCC 29212, Salmonella enterica subsp. I serovar
      Typhimurium 5408 and S. Typhimurium 5408CIP strains. The latter strain
      overproduces the AcrB transporter of the AcrAB-TolC efflux pump six-fold compared
      with its parent. Compounds 4-6 were also tested for similar activity against
      Escherichia coli AG100 wild-type strain and E. coli AG100TET8 that overproduces
      the AcrAB-TolC efflux pump. Evaluation of efflux activity was performed using a
      semi-automated method that measures accumulation of the universal efflux pump
      substrate ethidium bromide (EtBr). Some of the compounds significantly inhibited
      efflux of EtBr by MRSA COL(OXA) and E. faecalis ATCC 29212. A correlation between
      activity and the topological polar surface area of the compounds was found for
      MRSA COL(OXA).

PMID- 21075605
TI  - Risk factors and outcome of extended-spectrum beta-lactamase-producing
      Enterobacter cloacae bloodstream infections.
AB  - Enterobacter cloacae is a major nosocomial pathogen that causes serious
      infections, including bloodstream infections (BSIs). The clinical significance of
      extended-spectrum beta-lactamase (ESBL) production in E. cloacae is not well
      established. A multicentre, retrospective, cohort study was conducted to identify
      clinical characteristics of patients with E. cloacae BSI. ESBL production was
      confirmed by genotypic methods. A total of 159 patients with E. cloacae BSI were
      identified at three medical centres in north-eastern USA. Amongst them, 16
      patients (10.1%) harboured ESBL-producing E. cloacae. Independent risk factors
      for ESBL production included admission from a nursing home, the presence of a
      gastrostomy tube and history of transplant. For the outcome analysis, 15
      consecutive patients who had ESBL-producing E. cloacae BSI prior to the study
      were included. Amongst the 31 patients with ESBL-producing E. cloacae, 8, 9, 4
      and 2 patients received a carbapenem, cefepime, piperacillin/tazobactam and
      ciprofloxacin, respectively, as initial therapy. All patients who received a
      carbapenem (n=8) were alive at 28 days, whereas 7 (38.9%) of 18 patients who
      received a non-carbapenem antibiotic did not survive (P=0.06). Clinical failure
      at 96 h was observed in 2 (25.0%) of 8 patients who received a carbapenem and in
      14 (77.8%) of 18 patients who received a non-carbapenem antibiotic (P=0.03).
      Pulsed-field gel electrophoresis showed little clonality amongst the study
      isolates. The majority of isolates produced SHV-type ESBL, whereas two isolates
      produced CTX-M-type ESBL. Initial therapy with a carbapenem appears to be
      associated with improved clinical outcome in BSI due to ESBL-producing E.
      cloacae.

PMID- 21075606
TI  - Emergence of clonal groups O1:HNM-D-ST59, O15:H1-D-ST393, O20:H34/HNM-D-ST354,
      O25b:H4-B2-ST131 and ONT:H21,42-B1-ST101 among CTX-M-14-producing Escherichia
      coli clinical isolates in Galicia, northwest Spain.
AB  - CTX-M enzymes, mainly CTX-M-14 and CTX-M-15, have emerged as the most prevalent
      extended-spectrum beta-lactamase (ESBL) type produced by Escherichia coli in
      Spain, with successful dissemination of clonal group O25b:H4-B2-ST131 producing
      CTX-M-15 within the hospital and community settings. However, until now CTX-M-14
      producing E. coli in Spain had been shown to belong to a wide variety of
      serotypes with no predominance of a certain clonal group. In the present study,
      654 E. coli strains positive for ESBL production obtained between 2005 and 2008
      from inpatients and outpatients of four hospitals in Galicia, northwest Spain,
      were analysed. The strains were characterised with regard to ESBL enzymes,
      serotype, virulence genes, phylogenetic group, multilocus sequence type, and
      pulsed-field gel electrophoresis of XbaI-digested DNA. As a result, the emergence
      of certain clonal groups of extraintestinal pathogenic E. coli producing CTX-M-14
      has been detected in this geographic area, including O1:HNM-D-ST59, O15:H1-D
      ST393/ST1394, O20:H34/HNM-D-ST354, O25b:H4-B2-ST131 and ONT:H21,42-B1-ST101.
      These five clonal groups showed a high virulence potential as they harboured more
      than eight virulence factors, which could explain their successful dissemination.

PMID- 21075607
TI  - Fungicidal activity of human lactoferrin-derived peptides based on the
      antimicrobial alphabeta region.
AB  - Owing to the increasing number of infections in hospitalised patients caused by
      resistant strains of fungi, there is a need to develop new therapeutic agents for
      these infections. Naturally occurring antimicrobial peptides may constitute
      models for developing such agents. A modified peptide sequence (CFQWKRAMRKVR;
      HLopt2) based on amino acid residues 20-31 of the N-terminal end of human
      lactoferrin (hLF) as well as a double-sized human lactoferricin-like peptide
      (amino acid residues 16-40; HLBD1) were investigated for their antifungal
      activities in vitro and in vivo. By in vitro assay, HLopt2 was fungicidal at
      concentrations of 12.5-25 MUg/mL against Cryptococcus neoformans, Candida
      albicans, Candida krusei, Candida kefyr and Candida parapsilosis, but not against
      Candida glabrata. HLopt2 was demonstrated to have >= 16-fold greater killing
      activity than HLBD1. By inducing some helical formation caused by lactam bridges
      or by extending the assay time (from 2h to 20 h), HLBD1 became almost comparable
      with HLopt2 in its fungicidal activity. Killing of C. albicans yeast cells by
      HLopt2 was rapid and was accompanied by cytoplasmic and mitochondrial membrane
      permeabilisation as well as formation of deep pits on the yeast cell surface. In
      a murine C. albicans skin infection model, atopic treatment with the peptides
      resulted in significantly reduced yields of Candida from the infected skin areas.
      The antifungal activities of HLopt2 in vitro and in vivo suggest possible
      potential as a therapeutic agent against most Candida spp. and C. neoformans. The
      greatly improved antifungal effect of the lactam-modified HLBD1 indicates the
      importance of amphipathic helix formation for lethal activity.

PMID- 21075608
TI  - Discovering new antimicrobial agents.
AB  - Although there has been a relentless increase in resistance to antimicrobial
      agents amongst important bacterial pathogens throughout the world, it is well
      known that the number of new antimicrobial agents being brought to the market has
      undergone a steady decline in the past several decades. There are a number of
      reasons for this, which are detailed in this article, but there is also a great
      deal of continuing research to find new effective antimicrobials, much of it now
      being carried out in academic centres and especially in small biotechnology
      companies, rather than by large pharma. Whilst classic screening methods and
      chemical modification of known antimicrobial agents continue to produce potential
      leads for new antimicrobial agents, a number of other approaches are being
      investigated. These include the search for potentiators of the activity of known
      antimicrobial agents and the development of hybrid agents, novel membrane-active
      drugs, and inhibitors of bacterial virulence and pathogenesis. A number of new
      bacterial targets are also being exploited, as are bacteriophages and their lytic
      enzymes. Given the amount of investigation presently underway, it is clear that
      although the antibiotic pipeline is not as promising as it was half a century
      ago, it is far from dry.

PMID- 21075609
TI  - 8-years experience of fluoroquinolone susceptibility testing of multidrug
      resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand.

PMID- 21075610
TI  - Ganciclovir pharmacokinetics and suggested dosing in continuous venovenous
      haemodiafiltration.

PMID- 21075612
TI  - ERAD and ERAD tuning: disposal of cargo and of ERAD regulators from the mammalian
      ER.
AB  - The endoplasmic reticulum (ER) is the site of maturation for secretory and
      membrane proteins in eukaryotic cells. Unsuccessful folding attempts are
      eventually interrupted and most folding-defective polypeptides are dislocated
      across the ER membrane and degraded by cytosolic proteasomes in a complex series
      of events collectively defined as ER-associated degradation (ERAD). Uncontrolled
      ERAD activity might prematurely interrupt ongoing folding programs. At steady
      state, this is prevented by ERAD tuning, that is, the removal of select ERAD
      regulators from the ER and their degradation by proteasomes and by endo-lysosomal
      proteases. In Coronaviruses infected cells, the formation of LC3-I coated
      vesicles containing ERAD regulators cleared from the ER lumen is co-opted to
      anchor viral replication and transcription complexes to ER-derived membranes.

PMID- 21075611
TI  - Differential gene expression in mutant mice overexpressing or deficient in the
      serotonin transporter: a focus on urocortin 1.
AB  - Transcriptome analyses were performed in the anterior raphe area of mutant mice
      deficient in the serotonin transporter (5-HTT KO) or overexpressing this protein
      (5-HTT TG), which exhibit opposite changes in anxiety-related behavior. Among
      genes with altered expression, the gene encoding the neuropeptide urocortin 1 was
      down-regulated in 5-HTT KO and up-regulated in 5-HTT TG mice. Expression of the
      gene encoding cocaine-and-amphetamine-related-peptide, which colocalizes with
      urocortin 1, was also increased in 5-HTT TG mutants. Real-time RT-PCR confirmed
      these data and immunoautoradiographic labeling showed that parallel changes in
      neuropeptide levels were confined to the non-preganglionic Edinger-Westphal
      nucleus. Thus, 5-HTT expression correlates with that of urocortin 1, suggesting
      that this peptide can be involved in the behavioral changes observed in 5-HTT
      mutant mice.

PMID- 21075613
TI  - A transcuneiform fracture-dislocation of the midfoot.
AB  - Isolated fractures of the ossa cuneiformia are rare fractures of the foot and
      they usually occur in the context of a direct trauma. We report about a patient
      with a dislocation of the midfoot and concomitant fractures of the cuneiforme
      bones I-III due a car traffic accident. X-rays of the foot confirmed a lateral
      dislocation of the midfoot with multiple fractures of all ossa cuneiformia. An
      anterior-longitudinal approach was performed to access the ossa cuneiformia and
      the bases of the metatarsalia. Comminuted fractures of all ossa cuneiformia, a
      dislocation of the metatarsal bones I-III and a disruption of the Lisfranc
      ligament were found. The metatarsal bones I-III were stabilized by K-wires
      through the bases of the metatarsal bones into the os cuneiform. 6 months later
      the patient reached 92 points in the AOFAS-Score which correlates with a very
      good clinical result. We recommend a CT scan for the assessment of this injury
      since of the complex anatomy of the midfoot. Aim of all surgical procedures
      should be the restoration of anatomy, in particular of the longitudinal and the
      diagonal arch of the foot. The anterior, longitudinal approach provides a good
      overview and permits a direct access even to comminuted fractures.

PMID- 21075614
TI  - Membrane protein folding: how important are hydrogen bonds?
AB  - Water is an inhospitable environment for protein hydrogen bonds because it is
      polarizable and capable of forming competitive hydrogen bonds. In contrast, the
      apolar core of a biological membrane seems like an ideal environment for hydrogen
      bonds, and it has long been assumed that hydrogen bonding should be a powerful
      force driving membrane protein folding. Nevertheless, while backbone hydrogen
      bonds may be much stronger in membrane proteins, experimental measurements
      indicate that side chain hydrogen bond strengths are not strikingly different in
      membrane and water soluble proteins. How is this possible? I argue that model
      compounds in apolar solvents do not adequately describe the system because the
      protein itself is ignored. The protein chain provides a rich source of
      competitive hydrogen bonds and a polarizable environment that can weaken hydrogen
      bonds. Thus, just like water soluble proteins, evolution can drive the creation
      of potent hydrogen bonds in membrane proteins where necessary, but mitigating
      forces in their environment must still be overcome.

PMID- 21075615
TI  - Bacterial diversity, organic pollutants and their metabolites in two aeration
      lagoons of common effluent treatment plant (CETP) during the degradation and
      detoxification of tannery wastewater.
AB  - In this study, PCR-RFLP and GC-MS approaches were used to characterize the
      bacterial diversity, organic pollutants and metabolites during the tannery
      wastewater treatment process at common effluent treatment plant (CETP). Results
      revealed that the bacterial communities growing in aeration lagoon-I were
      dominated with Escherichia sp., Stenotrophomonas sp., Bacillus sp. and
      Cronobacter sp. while that of aeration lagoon-II prevailed with Stenotrophomonas
      sp., and Burkholderiales bacterium, respectively. The HPLC and GC-MS analysis
      revealed that most of the organic pollutants detected in untreated tannery
      wastewater samples were diminished from bacterial treated tannery wastewater
      samples. Only two pollutants i.e. L-(+)-lactic acid and acetic acid could not be
      degraded by bacteria whereas benzene and 2-hydroxy-3-methyl-butanoic acid was
      produced as new metabolites during the bacterial treatment of tannery wastewater
      in aeration lagoon II of CETP. Further, it was observed that after bacterial
      treatment, the toxicity of tannery effluent was reduced significantly allowing
      90% seed germination.

PMID- 21075616
TI  - New insights into membrane fouling in a submerged anaerobic membrane bioreactor
      based on characterization of cake sludge and bulk sludge.
AB  - A laboratory-scale submerged anaerobic membrane bioreactor (SAnMBR) treating
      thermomechanical pulping whitewater was operated for over 7 months to investigate
      and compare the characteristics of cake sludge and bulk sludge during stable
      state operation period. Serial analysis showed that cake sludge had a smaller
      particle size distribution (PSD), much higher specific filtration resistance
      (1.34*10(14) m/kg), 1.5 times higher bound EPS and significantly different
      microbial community as compared with bulk sludge. Further analysis indicated that
      small flocs, bound EPS and inorganic materials play important role in cake
      formation process. The formed cake layer was found to have a heterogeneous
      structure. The results obtained in this study indicated that cake formation
      process started from attachment of small flocs and/or specific bacterial clusters
      which colonize the surface of the membrane and provide enhanced conditions that
      allow for cake formation to progress.

PMID- 21075617
TI  - Mathematical modeling of hydrolysate diffusion and utilization in cellulolytic
      biofilms of the extreme thermophile Caldicellulosiruptor obsidiansis.
AB  - In this study, a hydrolysate diffusion and utilization model was developed to
      examine factors influencing cellulolytic biofilm morphology. Model simulations
      using Caldicellulosiruptor obsidiansis revealed that the cellulolytic biofilm
      needs to generate more hydrolysate than it consumes to establish a higher than
      bulk solution intra-biofilm substrate concentration to support its growth. This
      produces a hydrolysate surplus that diffuses through the thin biofilm structure
      into the bulk solution, which gives rise to a uniform growth rate and hence the
      homogeneous morphology of the cellulolytic biofilm. Model predictions were tested
      against experimental data from a cellulose-fermenting bioreactor and the results
      were consistent with the model prediction and indicated that only a small
      fraction (10-12%) of the soluble hydrolysis products are utilized by the biofilm.
      The factors determining the rate-limiting step of cellulolytic biofilm growth are
      also analyzed and discussed.

PMID- 21075618
TI  - Characterisation of source-separated household waste intended for composting.
AB  - Large-scale composting of source-separated household waste has expanded in recent
      years in the Nordic countries. One problem can be low pH at the start of the
      process. Incoming biowaste at four composting plants was characterised
      chemically, physically and microbiologically. The pH of food waste ranged from
      4.7 to 6.1 and organic acid concentration from 24 to 81 mmol kg(-1). The
      bacterial diversity in the waste samples was high, with all samples dominated by
      Gammaproteobacteria, particularly Pseudomonas and Enterobacteria (Escherichia
      coli, Klebsiella, Enterobacter). Lactic acid bacteria were also numerically
      important and are known to negatively affect the composting process because the
      lactic acid they produce lowers the pH, inhibiting other bacteria. The bacterial
      groups needed for efficient composting, i.e. Bacillales and Actinobacteria, were
      present in appreciable amounts. The results indicated that start-up problems in
      the composting process can be prevented by recycling bulk material and compost.

PMID- 21075619
TI  - Monitoring the removal of nitrogen by applying a nitrification-denitrification
      process in a Sequencing Batch Reactor (SBR).
AB  - In this study the evaluation of nitrogen removal in wastewater from a meat
      products processing company was performed, using a Sequencing Batch Reactor (SBR)
      at pilot scale. The phases of the SBR operation were: filling, reaction (aeration
      and intermittent anoxia), sedimentation and discharge. In each of these phases
      analyses of ammonium (NH(4)(+)), nitrite (NO(2)(-)), nitrate (NO(3)(-)), pH and
      dissolved oxygen (DO) were carried out to monitor the process of nitrification
      denitrification. The results showed that stage IV had the best performance (2.49
      g COD(F)/Ld and 1.02 g NH(4)(+)-N/Ld) with a NH(4)(+)-N removal of 71%. The
      transformation of much of the NH(4)(+)-N to gaseous nitrogen was confirmed, with
      the concentration of NO(2)(-)-N and NO(3)(-)-N increasing during the reaction
      phase but decreasing in the effluent due to its transformation to gaseous
      nitrogen.

PMID- 21075620
TI  - Evaluation of biological nutrient removal from wastewater by Twin Circulating
      Fluidized Bed Bioreactor (TCFBBR) using a predictive fluidization model and
      AQUIFAS APP.
AB  - A two-phase and three-phase predictive fluidization model based on the
      characteristics of a system such as media type and size, flow rates, and reactor
      cross sectional area was proposed to calculate bed expansion, solid, liquid and
      gas hold up and specific surface area (SSA) of the biofilm particles. The model
      was subsequently linked to 1d AQUIFAS APP software (Aquaregen) to model
      biological nutrient removal in two phase (anoxic) and three phase (aerobic)
      fluidized bed bioreactors. The credibility of the proposed model for biological
      nutrient removal was investigated using the experimental data from a Twin
      Circulating Fluidized Bed Bioreactors (TCFBBR) treating synthetic and municipal
      wastewater. The SSA of bio-particles and volume of the expanded bed were
      simulated as a function of operational parameters. Two-sided t-tests demonstrated
      that simulated SCOD, NH(4)-N, NO(3)-N, TN, VSS and biomass yields agreed with the
      experimental values at the 95% confidence level.

PMID- 21075621
TI  - Production of volatile fatty acids by fermentation of waste activated sludge pre
      treated in full-scale thermal hydrolysis plants.
AB  - This work focuses on fermentation of pre-treated waste activated sludge (WAS) to
      generate volatile fatty acids (VFAs). Pre-treatment by high-pressure thermal
      hydrolysis (HPTH) was shown to aid WAS fermentation. Compared to fermentation of
      raw WAS, pre-treatment enabled a 2-5x increase in VFA yield (gVFA(COD)gTCOD(-1))
      and 4-6x increase in VFA production rate (gVFA(COD) L(-1) d(-1)). Three sludges,
      pre-treated in full-scale HPTH plants, were fermented. One was from a plant
      processing a mix of primary sludge and WAS and the other two from plants
      processing solely WAS. The HPTH plants solubilised suspended matter, evidenced by
      a 20-30% decrease in suspended solids and an increase of soluble COD : total COD
      from 0.04 to 0.4. Fermentation of the three sludges yielded similar VFA
      concentrations (15-20gVFA(COD) L(-1)). The yields were largely independent of
      retention time (1 d-6 d) and temperature (42 degrees C, 55 degrees C). Also, the
      product spectrum depended mostly on the composition of the sludge rather than on
      operating conditions.

PMID- 21075622
TI  - Evaluation of maturity and stability parameters of composts prepared from agro
      industrial wastes.
AB  - The objective of this study was to evaluate changes in physical, chemical and
      biological parameters to assess the maturity and stability of composts prepared
      from mixture of different farm and agro-industrial wastes over a period of 150
      days. All the composts appeared granular, dark grey in color without foul odor
      and attained an ambient temperature at 120 days of composting indicating the
      stable nature of composts. Correlation analysis showed that the optimal values of
      the selected parameters for our experimental conditions are as follows: organic
      matter loss >42%, C:N ratio <15, water soluble organic carbon (C(w)):organic N
      (N(org)) ratio <0.55, humic acid (HA):fulvic acid (FA) ratio >1.9, humification
      index (HI) >30%, cation exchange capacity (CEC):total organic carbon (TOC) ratio
      >1.7 and germination index (GI) >70%. Compost enriched with sewage sludge,
      pressmud and poultry waste matured earlier compared to composts either enriched
      with distillery effluent or un-enriched.

PMID- 21075623
TI  - Laboratory experiment to determine the potential of two macroalgae from the
      Russian Far-East as biofilters for integrated multi-trophic aquaculture (IMTA).
AB  - Two local macroalgal species (Undaria pinnatifida and Gracilaria vermiculophylla)
      were tested in laboratory experiments to determine their nutrient uptake
      potential and their physiological response to waste water effluents from a
      mariculture project on bivalve mollusks (mussels). No negative effects on the
      growth and photosynthesis rates of the algae were detected. High nutrient uptake
      rates and high nutrient removal efficiency were measured in both tested species.
      We propose that U. pinnatifida be introduced into IMTA systems during the cold
      water season to remove nutrients from cultured animals. The culture of this
      species can be alternated with that of G. vermiculophylla during warm-water
      season in order to provide a longer biofiltration period.

PMID- 21075624
TI  - Biotransformation and biomonitoring of phenylurea herbicide diuron.
AB  - A Gram-positive, Micrococcus sp. strain PS-1 isolated from diuron storage site
      was studied for its capability of biotransformation of phenylurea herbicide
      diuron to a secondary metabolite, 1-(3,4-dichlorophenyl)urea (DCPU) for
      bioconjugation and antibody development applications. The metabolite formed
      associated with profound changes in bacterial cell morphology demonstrated
      increase in the degradation kinetics of diuron in presence of small quantity of a
      surfactant. The synthesized metabolite identified by chromatographic and mass
      spectrometry techniques was conjugated with carrier protein, and used as an
      immunogen for antibodies production. The generated antibody was highly specific,
      demonstrating excellent sensitivity against diuron. The antibody was used as
      receptor molecules in standard fluorescence immunoassay (FIA) format showing
      detection limit of 0.01 ng/mL in the optimum working concentration range of
      diuron with good signal precision (~2%). The study presented first time the
      degradation pathway of herbicide by specific microorganism to synthesize hapten
      for bioconjugation and immunoassay development.

PMID- 21075625
TI  - The first characterized asparaginase from a basidiomycete, Flammulina velutipes.
AB  - Flammulina velutipes enjoys high popularity as an edible mushroom in Asian
      cuisines. Investigating the secretion of peptidases in nutrient media enriched
      with gluten, an enzyme was noticed that catalyzed the deamidation of L-asparagine
      and L-glutamine. The enzyme was purified to electrophoretic homogeneity by
      foaming and SEC. PAGE analysis revealed a protein of about 85 kDa with 13 kDa
      subunits indicating a hexameric protein. Degenerated primers were deduced from
      peptide fragments and the complete coding sequence of 372 bp was determined. The
      gene of Flammulina velutipes asparaginase (FvNase) over expressed in E. coli
      achieved an L-asparagine-hydrolyzing activity of 16 U/mL in crude extract, which
      was five times higher than its L-glutamine-hydrolyzing ability. The enzyme showed
      a pH-optimum at pH 7, remarkable tolerance towards elevated temperature and
      sodium chloride concentration in both the native and recombinant form, and no
      significant homology to any conserved domains of published asparaginases or
      glutaminases.

PMID- 21075626
TI  - Mesophilic and thermophilic aerobic batch biodegradation, utilization of carbon
      and nitrogen sources in high-strength wastewater.
AB  - This study compares organic and nitrogen removals of thermophilic and mesophilic
      aerobic processes. The experiments were performed in three 7.2L sequential batch
      reactors (SBRs) operated at 30, 47 and 60 degrees C. Molasses based synthetic
      wastewater consisting chemical oxygen demand (COD): 11,200 mg/L, total kheljal
      nitrogen (TKN): 770 mg/L, ammonical nitrogen (NH(4)): 560 mg/L was the feed
      medium. Biokinetic parameters, COD, NH(4)(+) and TKN removal efficiencies were
      compared under six different operating conditions. Five times lower sludge
      production and similar COD removal were observed in thermophilic SBRs compared to
      mesophilic SBR under 8.25 kg COD/m(3)d loading rate. However at 24.75 kg
      COD/m(3)d there were no differences in terms of sludge production while COD
      removals were varied as 59%, 80% and 82% at 30, 47 and 60 degrees C respectively.
      A mechanism was developed to understand the varying behaviors of thermophilic
      aerobic process. Stripping is the major mechanism for nitrogen removal in
      thermophilic SBRs.

PMID- 21075627
TI  - Inhalation by design: dual pharmacology beta-2 agonists/M3 antagonists for the
      treatment of COPD.
AB  - This paper describes the successful design and development of dual pharmacology
      beta-2 agonists-M3 antagonists, for the treatment of chronic obstructive
      pulmonary disorder using the principles of 'inhalation by design'. A key feature
      of this work is the combination of balanced potency and pharmacodynamic duration
      with desirable pharmacokinetic and material properties, whilst keeping synthetic
      complexity to a minimum.

PMID- 21075628
TI  - The discovery of novel indole-2-carboxamides as cannabinoid CB(1) receptor
      antagonists.
AB  - The discovery and structure-activity relationship of a novel series of indole-2
      carboxamide antagonists of the cannabinoid CB(1) receptor is disclosed. Compound
      26i was found to be a high potency, selective cannabinoid CB(1) antagonist.

PMID- 21075629
TI  - Synthesis and biological evaluation of N-alkylated 8-oxybenz[c]azepine
      derivatives as selective PPARdelta agonists.
AB  - We describe the discovery of small molecule benzazepine derivatives as agonists
      of human peroxisome proliferator-activated receptor delta (PPARdelta) that
      displayed excellent selectivity over the PPARalpha and PPARgamma subtypes.
      Compound 8 displayed good PK in the rat and efficacy in upregulation of pyruvate
      dehydrogenase kinase, isozyme 4 (PDK4) mRNA in human primary myotubes, a
      biomarker for increased fatty acid oxidation.

PMID- 21075630
TI  - Design, synthesis, and structure-activity relationships of indole-3-heterocycles
      as agonists of the CB1 receptor.
AB  - Novel indole-3-heterocycles were designed and synthesized and found to be potent
      CB1 receptor agonists. Starting from a microsomally unstable lead 1, a
      bioisostere approach replacing a piperazine amide was undertaken. This was found
      to be a good strategy for improving stability both in vitro and in vivo. This led
      to the discovery of 24, which had an increased duration of action in the mouse
      tail flick test in comparison to the lead 1.

PMID- 21075631
TI  - Radiolabeling and preliminary biological evaluation of a (99m)Tc(CO)(3) labeled
      3,3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide) derivative as a potential
      SPECT tracer for in vivo visualization of necrosis.
AB  - N,N'-bis(diethylenetriamine pentaacetic acid)-3,3'-(benzylidene)-bis-(1H-indole-2
      carbohydrazide) (bis-DTPA-BI) was radiolabeled with (99m)Tc(CO)(3). The resulting
      (99m)Tc(CO)(3)-bis-DTPA-BI was characterized (LC-MS) and evaluated as a potential
      SPECT tracer for imaging of necrosis in Wistar rats with a reperfused partial
      liver infarction and Wistar rats with ethanol induced muscular necrosis. To study
      the specificity, uptake of (99m)Tc(CO)(3)-bis-DTPA-BI was also studied in a mouse
      model of Fas-mediated hepatic apoptosis. The obtained results indicate that
      (99m)Tc(CO)(3)-bis-DTPA-BI displays selective uptake in necrotic tissue and can
      be used for in vivo visualization of necrosis by SPECT.

PMID- 21075632
TI  - Bioisosteric approach to the discovery of imidazo[1,2-a]pyrazines as potent
      Aurora kinase inhibitors.
AB  - Our continued effort toward the development of the imidazo[1,2-a]pyrazine
      scaffold as Aurora kinase inhibitors is described. Bioisosteric approach was
      applied to optimize the 8-position of the core. Several new potent Aurora A/B
      dual inhibitors, such as 25k and 25l, were identified.

PMID- 21075633
TI  - Novel pyrazole-3-carboxamide derivatives as cannabinoid-1 (CB1) antagonists:
      journey from non-polar to polar amides.
AB  - The synthesis and biological evaluation of novel pyrazole-3-carboxamide
      derivatives as CB1 antagonists are described. As a part of eastern amide SAR,
      various chemically diverse motifs were introduced. In general, a range of
      modifications were well tolerated. Several molecules with high polar surface area
      were also identified as potent CB1 receptor antagonists. The in vivo proof of
      principle for weight loss is exemplified with a lead compound from this series.

PMID- 21075634
TI  - Replacing the 2'-oxygen with an exocyclic methylene group reverses the
      stabilization effects of alpha-L-LNA.
AB  - The synthesis and hybridization properties of an alpha-L-LNA analog where the 2'
      oxygen atom is replaced with an exocyclic methylene group is reported. Contrary
      to the beta-D series where the exocyclic methylene group is extremely well
      tolerated, this group was very poorly tolerated in the alpha-L-series and lead to
      duplex destabilization. Modeling studies showed that the exocyclic methylene
      group results in a steric clash with the nucleobase 3' to the modified residue.
      Based on this structural model one can anticipate that replacing the 2'-oxygen
      atom of alpha-L-LNA with larger groups is likely to be detrimental to duplex
      stability. The model also provides insights into what type of 2',4'-bridges are
      most likely to be tolerated in alpha-L-LNA modified oligonucleotide duplexes.

PMID- 21075635
TI  - Synthesis and antifungal evaluation of 6-hydroxy-1H-carbazole-1,4(9H)-diones.
AB  - 6-Hydroxy-1H-carbazole-1,4(9H)-diones were synthesized and tested for in vitro
      antifungal activity against two pathogenic strains of fungi. Among them tested,
      many compounds showed good antifungal activity. The results suggest that 6
      hydroxy-1H-carbazole-1,4(9H)-diones would be potent antifungal agents.

PMID- 21075636
TI  - Comprehensive lysine acetylomes emerging from bacteria to humans.
AB  - Recent proteomic studies reveal that 5-10% of mammalian and bacterial proteins
      undergo lysine acetylation, a post-translational modification that adds an acetyl
      group to the E-amino group of lysine residues. Many of these proteins are not
      canonical targets, such as histones and transcription factors, suggesting that
      this modification plays a much wider role than previously appreciated. These
      studies also suggest that lysine acetylomes are at least comparable with (if not
      larger than) phosphoproteomes. Although many of the newly identified acetylation
      events still require validation, they constitute an important framework for
      further research and the development of new drugs useful in treating a variety of
      pathologies. Herein, we summarize these proteomic studies and highlight recent
      reports linking lysine acetylation to heterochromatin assembly, sister chromatid
      cohesion, cytoskeleton dynamics, autophagy, receptor signaling, RNA processing
      and metabolic control.

PMID- 21075637
TI  - High-throughput identification of antibacterials against methicillin-resistant
      Staphylococcus aureus (MRSA) and the transglycosylase.
AB  - To identify new transglycosylase inhibitors with potent anti-methicillin
      resistant Staphylococcus aureus (MRSA) activities, a high-throughput screening
      against Staphylococcus aureus was conducted to look for antibacterial cores in
      our 2M compound library that consists of natural products, proprietary
      collection, and synthetic molecules. About 3600 hits were identified from the
      primary screening and the subsequent confirmation resulted in a total of 252
      compounds in 84 clusters which showed anti-MRSA activities with MIC values as low
      as 0.1 MUg/ml. Subsequent screening targeting bacterial transglycosylase
      identified a salicylanilide-based core that inhibited the lipid II polymerization
      and the moenomycin-binding activities of transglycosylase. Among the collected
      analogues, potent inhibitors with the IC(50) values below 10 MUM against
      transglycosylase were identified. The non-carbonhydrate scaffold reported in this
      study suggests a new direction for development of bacterial transglycosylase
      inhibitors.

PMID- 21075638
TI  - Synthesis and pharmacological properties of novel hydrophilic 5-HT4 receptor
      antagonists.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is an important signalling molecule in the
      human body. The 5-HT(4) serotonin receptor, coupled to the G protein G(s), plays
      important physiological and pathophysiological roles in the heart, urinary
      bladder, gastrointestinal tract and the adrenal gland. Both 5-HT(4) antagonists
      and agonists have been developed in the aim to treat diseases in these organs. 5
      HT(4) agonists might have beneficial effects in the central nervous system (CNS)
      and therefore, 5-HT(4) antagonists might cause CNS side effects. In this study,
      we have developed new amphoteric 5-HT(4) antagonists. A series of cyclic indole
      amide derivatives possessing an oxazine ring and a piperidine alkane carboxylic
      acid side chain and the corresponding prodrug esters were synthesized and their
      binding to 5-HT(4) receptors and antagonist properties were evaluated. In
      addition, an indole ester without the oxazine ring and the corresponding indole
      amide derivatives were also tested. Octanol-water distribution (LogD(Oct7.4)) was
      tested for some of the synthesized ligands. The main structure-affinity
      characteristics of the 5-HT(4) compounds tested were that the prodrug esters show
      higher affinity than their corresponding free acids, indole esters show higher
      affinity than the corresponding amides and ligands containing the oxazine ring in
      the indole skeleton show higher affinity than indole derivatives not containing
      the ring. One representative prodrug ester and its corresponding free acid were
      tested for binding on a panel of receptors and showed preserved selectivity for
      the 5-HT(4) receptor. These new molecules may be useful to target peripheral 5
      HT(4) receptors.

PMID- 21075640
TI  - Characterization of the response to moisture of talc and perlite in the
      environmental scanning electron microscope.
AB  - This article focuses on the application of ESEM to study the dynamic interaction
      of hydrophobic and hydrophilic filler materials of interest for the cosmetic and
      pharmaceutical industries. The ability of ESEM to attain different thermodynamic
      stages was used to record real-time information of hydration and dehydration
      processes of those materials in the presence of water and sweat (used as a model
      physiological fluid). This information is of great importance to understand the
      behavior of a product containing those fillers as well as to identify potential
      processing issues related to the interaction of the filler with moisture.

PMID- 21075641
TI  - Study of DNA damage with a new system for irradiation of samples in a nuclear
      reactor.
AB  - In this paper, we report results of a quantitative analysis of the effects of
      neutrons on DNA, and, specifically, the production of simple and double breaks of
      plasmid DNA in aqueous solutions with different concentrations of free-radical
      scavengers. The radiation damage to DNA was evaluated by electrophoresis through
      agarose gels. The neutron and gamma doses were measured separately with
      thermoluminescent detectors. In this work, we have also demonstrated usefulness
      of a new system for positioning and removing samples in channel BH#3 of the IEA
      R1 reactor at the Instituto de Pesquisas Energeticas e Nucleares (Brazil) without
      necessity of interrupting the reactor operation.

PMID- 21075642
TI  - Glucose-insulin-potassium therapy in adult patients undergoing cardiac surgery: a
      meta-analysis.
AB  - Glucose-insulin-potassium (GIK) has long been used as adjuvant treatment for
      patients with serious cardiovascular disease. Although many studies have reported
      their results based on GIK therapy in the setting of heart surgery, the outcomes
      remain controversial and inconclusive. The aim of this meta-analysis of
      randomized controlled trials (RCTs) was to determine the clinical effects of GIK
      in adult cardiac surgery patients. Electronic databases and manual
      bibliographical searches were conducted. A meta-analysis of all RCTs comparing
      GIK with control in heart surgery was performed. Data for all-causes mortality
      (within 2 months after surgery), perioperative myocardial infarction,
      postoperative inotropic support, atrial fibrillation, cardiac index, durations of
      intensive unit care stay and total hospital stay were extracted, and we
      summarized the combined results of the data of the RCTs as relative risk (RR),
      with 95% confidence intervals (CIs). A total of 33 RCTs including 2113 patients
      were assessed in this study. GIK infusion was associated with significantly fewer
      perioperative myocardial infarctions (RR = 0.63, 95% CI 0.42-0.95), less
      inotropic support requirement (RR = 0.66, 95% CI 0.45-0.96), better postoperative
      cardiac index (weighted mean difference (WMD) = 0.43, 95% CI 0.31-0.55), and
      reduced length of stay in the intensive care unit (WMD = -7.96, 95% CI -13.36 to 
      2.55). Further analysis showed that diabetic patients were benefited from GIK
      with glycemic control, but not GIK infusion without glucose control. GIK
      significantly reduced myocardial injury and improved hemodynamic performance in
      patients undergoing cardiac surgery. Glycemic control with GIK might be required
      for cardiac surgery patients with diabetes.

PMID- 21075643
TI  - Elective pectus bar removal following Nuss procedure for pectus excavatum: a
      single-institution experience.
AB  - OBJECTIVE: Very few data are available on complications following elective bar
      removal after the Nuss procedure for pectus excavatum. The objective of this
      study was to investigate the data from 343 consecutive patients. METHODS: From
      2003 to 2009, 343 patients (85% males) had their pectus bar removed. Nine
      patients were excluded because of bar removal within the first year after
      implantation. Data were recorded from hospital records regarding: operation time,
      formation of callus around the bar, unilateral or bilateral incision,
      complications, postoperative hospital stay and if a senior resident or an intern
      performed the operation. RESULTS: The median age at the time of bar removal was
      19.1 years. The median time for removal after insertion of the bar was 1139 days
      (range 641-2575 days). The median operation time was 34 min (range 5-183 min).
      The operation time depended on the formation of callus around the bar (p<0.0001),
      numbers of bars to be removed (p<0.0002), the need for bilateral incision
      (p<0.0001) and the charge of the surgeon performing the operation (p<0.0008).
      Eight patients (2.4%) had complications after the surgery. Five patients had
      pneumothorax, of which three were treated with chest tubes, and two controlled
      with chest X-ray. Three patients had hemothorax. Two were treated with a chest
      tube and the third required open surgery. Most of the patients were discharged on
      the day of surgery (94%) or the day after surgery (4%). Only six (2%) required
      more than a single day of hospitalization. CONCLUSIONS: Bar removal following the
      Nuss procedure is a quick and safe operation with very few complications.
      Occurrence of complications is not dependent on the experience of the surgeon.

PMID- 21075644
TI  - Effects of communication skills training and a Question Prompt Sheet to improve
      communication with older cancer patients: a randomized controlled trial.
AB  - A randomized pre- and post-test control group design was conducted in 12 oncology
      wards to investigate the effectiveness of an intervention, existing of a
      communication skills training with web-enabled video feedback and a Question
      Prompt Sheet (QPS), which aimed to improve patient education to older cancer
      patients (>=65 years). The effects were studied by analyzing questionnaires and
      video recordings of patient education sessions preceding chemotherapy with 210
      different patients. Patients' recall of information was the primary outcome of
      the study. Recall was checked against the actual communication in the video
      recordings. Moreover, communication skills were assessed by observing the extent
      to which nurses implemented 67 communication aspects, categorized in seven
      dimensions, using the QUOTE(chemo). Experimental nurses demonstrated a
      significant intervention effect on communicating realistic expectations. Within
      group improvements were measured in the experimental group for tailored
      communication, affective communication and interpersonal communication. Although
      the use of a QPS significantly increased question asking, only limited results
      were found on older patients' recall scores. The overall proportion recall of
      recommendations showed a marginally significant pre-/post-change in proportion
      recall in favour of the experimental group and there was a significant pre-/post
      change in two out of six sub-categories. The results indicate that nurses'
      communication skills can be improved by communication skills training. More
      research is needed to understand the difficult relationship between patient
      provider communication and recall of information.

PMID- 21075646
TI  - Predictors of mortality following acute stroke: a cohort study with 12 years of
      follow-up.
AB  - In this study, we investigated predictors for long-term all-cause mortality in a
      cohort of patients hospitalized for acute stroke. We prospectively followed 550
      patients aged >= 60 years who were consecutively admitted within 24 hours of
      sustaining acute stroke. The patients were followed for 12 years or until death,
      whichever came first. Multivariate Cox regression models were used to analyze
      predictors of all-cause mortality, with the following independent variables: age,
      sex, living alone, previous stroke, ischemic heart disease, atrial fibrillation,
      hypertension, diabetes, cancer, current smoker, hemorrhagic stroke, treatment in
      an acute stroke unit, and stroke severity (measured with the Scandinavian Stroke
      Scale). The 12-year mortality rate was 86.5%. In a multivariate model, all-cause
      mortality was associated with the following variables: age (hazard ratio, 1.08;
      95% confidence interval, 1.07-1.10), male sex (1.69, 1.40-2.05), previous stroke
      (1.34, 1.08-1.65), ischemic heart disease (1.30, 1.02-1.64), diabetes (1.74, 1.36
      2.23), hemorrhagic stroke (1.58, 1.20-2.08), and stroke severity (1.03, 1.03
      1.04); Age, male sex, stroke severity, ischemic heart disease, diabetes, and
      hemorrhagic stroke were all independently associated with an increased risk of
      all-cause mortality over the 12-year period after stroke.

PMID- 21075645
TI  - Evaluation of exercise-induced muscle damage by surface electromyography.
AB  - OBJECTIVE: To investigate the feasibility of a non-invasive and instant method to
      evaluate the degree of exercise-induced muscle damage. METHODS: Thirteen male
      college athletes (23.4+/-1.0year, 180.03+/-3.51cm, 75.93+/-6.70kg) took part in
      the trial. Measures included serum creatine kinase (CK) after eccentric and
      endurance exercise, and surface electromyography (sEMG) during knee extension and
      flexion on a Biodex unit. Relation analysis was employed between sEMG and serum
      CK after the eccentric and endurance exercise. RESULTS: There were positive
      correlations between serum CK at 24 and 48h after eccentric exercise and the AREA
      of sEMG for the slow isokinetic contraction before eccentric exercise (r=0.69,
      P<0.01 and 0.64, P<0.05, respectively). The zero crossing rate (ZCR) immediately
      after exercise was negatively correlated with serum CK at 48h after exercise for
      the slow and fast tests (r=-0.63 and -0.59, P<0.05, respectively). Mean power
      frequency (MPF) and ZCR of sEMG at 6h post endurance exercise were positively
      correlated with serum CK at 24h (r=0.73 and 0.69, P<0.05, respectively) for the
      fast isokinetic test. CONCLUSIONS: Exercise-induced muscle damage as evaluated by
      serum CK was associated with the AREA of sEMG after eccentric exercise. The ZCR
      of sEMG was a good predictor of muscle damage after endurance exercise.

PMID- 21075647
TI  - Effects of simvastatin on pulmonary C-fiber sensitivity in rats with
      monocrotaline-induced pulmonary hypertension.
AB  - BACKGROUND: The possible mechanisms of simvastatin attenuating pulmonary
      hypertension (PH) have been widely investigated in pulmonary vascular and
      hemodynamic systems, but few studies have examined the difference in respiratory
      response mediated by pulmonary C fibers (PCF) in animal models of PH. We
      hypothesized that PCF sensitivity would differ from normal in monocrotaline
      induced pulmonary hypertension (MCT-PH) rats and the effects of simvastatin
      treatment would involve not only the pulmonary circulatory system, but also PCF
      sensitivity. METHODS: The PCF sensitivity was investigated by measuring the
      apneic durations evoked by 3 chemical stimulants: capsaicin; alpha,beta-methylene
      adenosine triphosphate; and phenylbiguanide. The effects of simvastatin on PCF
      sensitivity were evaluated in the MCT-PH rat model. RESULTS: The sensitivity of
      PCF was increased significantly after monocrotaline (MCT) application for 21
      days. Bilateral vagatomy and high-dose perivagal capsaicin (250 MUg/ml) treatment
      both blocked the PCF hypersensitivity induced by MCT. Three days of simvastatin
      (5 mg/kg) treatment significantly reduced the hypersensitive status of PCF. In
      MCT-PH rats, reactive oxygen species (ROS) production was significantly elevated
      in both blood and bronchoalveolar lavage, but both showed a significantly
      decrease after simvastatin treatment. These potential benefits of simvastatin
      were all abolished by co-application of tin protoporphyrin-IX (SnPP), a specific
      heme oxygenase-1 (HO-1) inhibitor. CONCLUSION: Simvastatin treatment in MCT-PH
      rats not only attenuated pulmonary hypertension, but also desensitized PCF
      hypersensitivity and decreased the production of ROS. These cholesterol
      independent effects were mainly through the HO-1 pathway and may all contribute
      to the therapeutic effects of PH treatment.

PMID- 21075648
TI  - The neural control of mood: the possible role of the adrenergic system in the
      medulla.
AB  - Mood in humans is a complex phenomenon that integrates emotion (e.g. happiness
      and sadness), cognition, perception, ideation, and action in a coherent manner.
      In bipolar disorder extremes of mood (up or down) occur outside the normal range,
      in which all the above functions are coherently affected. Mood is controlled by a
      series of separate but interactive brain circuits that involve much of the brain,
      but particularly the limbic system. The question addressed in this paper is
      whether the coordination of all these separate systems into one coherent
      functional mood is mediated by non-linear dynamics acting between these systems
      as equal participants; or whether it is affected by a single master regulator
      controlling the others. The possible roles, as master regulators, of non-linear
      dynamically linked populations of neurons, and of the C1-C3 adrenergic nuclei in
      the medulla is discussed.

PMID- 21075649
TI  - The response to valve injury. A paradigm to understand the pathogenesis of heart
      valve disease.
AB  - Human heart valve diseases have become an important topic in cardiovascular
      pathology and medicine. These diseases have different etiologies and
      manifestations. However, the most common ones including calcific aortic stenosis
      have histopathological features that are best characterized as a "response to
      tissue injury" similar to ones seen in numerous tissues and organs. The valve
      interstitial cell is the prevalent cell type in the valve and is likely the
      master cell which ultimately regulates cell and molecular repair processes within
      the valve that involve autocrine and paracrine processes as well as interactions
      with the matrix components of the valve. This presentation explores the concept
      of "response to tissue injury" in understanding the pathogenesis of calcific
      aortic stenosis.

PMID- 21075650
TI  - Glucose regulation influences treatment outcome in ranibizumab treatment for
      diabetic macular edema.
AB  - PURPOSE: To evaluate the effect of glucose regulation on intravitreal ranibizumab
      injection for clinically significant diabetic macular edema (DME). METHODS: This
      retrospective study enrolled 65 eyes of 65 patients with persistent DME treated
      with intravitreal ranibizumab injection. The main outcome measures were the
      change in best corrected visual acuity (BCVA), the central subfield macular
      thickness (CSMT) recorded with optical coherence tomography (OCT), and its
      correlation with the serum hemoglobin A(1c) values (HbA(1c)). RESULTS: The study
      included 24 (36.9%) female and 41 (63.1%) male patients with a mean age of
      58.90+/-9.45 years. The mean HbA(1c) of the enrolled patients was 8.25+/-1.74%
      (range 5.7-12.7%). The median value of BCVA at baseline examination was 20/80 (52
      letters), and the median CSMT was 468 MUm (range 255-964 MUm). In the final
      control after 4-6 weeks following injection, the median value of BCVA increased
      to 20/50 (59.50 letters) and the median CSMT decreased to 310 MUm (range 129-652
      MUm). This change in BCVA and macular thickness was found to be significant
      (P<.001 for both). There was no correlation between BCVA and the change in
      macular thickness (coefficient=0.04, P=.78). The serum HbA(1c) values were found
      to be negatively correlated with the change in CSMT (coefficient=-0.50, P<.001).
      CONCLUSIONS: The results of intravitreal ranibizumab injection for DME
      demonstrated a beneficial effect on visual acuity and a decrease in CSMT which is
      inversely correlated with the serum HbA(1c) level.

PMID- 21075651
TI  - Potential biomarkers of osteonecrosis in Gaucher disease.
AB  - BACKGROUND: To investigate the relationship between chemokines and cytokines and
      osteonecrosis in Gaucher disease, we conducted multiplex assays in a cohort of
      100 adult patients. METHODS: Mean age was 45 years (18-86); 92 Gaucher patients
      received imiglucerase (median duration 8 years (2-18)). Forty-three had
      experienced osteonecrosis (ON), and eight had ON despite enzyme therapy. Serum
      cytokines/chemokines were determined by fluorimetric bead arrays in samples from
      Gaucher patients and healthy volunteers (10 males and 10 females). Intra-assay
      and inter-assay coefficients of variation were 2%-9.8% and 5.6%-15%,
      respectively. RESULTS: VEGF and CCL5/RANTES did not differ between Gaucher and
      control samples. Concentrations of CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL2/MCP-1,
      CXCL8/IL-8, IL-1ra and CCL18/PARC were elevated in Gaucher patients (p<0.05 for
      each). Median CCL4/MIP-1beta, CXCL8/IL-8, CCL5/RANTES and CCL18/PARC
      concentrations were greater in the 43 osteonecrosis patients (88.6 pg/mL, 30.5
      pg/mL, 89.6 ng/mL and 434 ng/mL, respectively) compared with the 57 patients who
      had no evidence of osteonecrosis (medians of 59.4, 13.3, 62.7 and 283,
      respectively, p<0.05). Moreover, the eight patients with ON despite imiglucerase
      had median concentrations of CCL3/MIP-1alpha, CCL4/MIP-1beta, CXCL8/IL-8,
      CCL5/RANTES and CCL18/PARC (73.2, 120.9, 36.3 pg/mL, 105 and 767 ng/mL,
      respectively), which significantly exceeded the values in 84 patients now free of
      ON (52.3, 71.2, 16.5 pg/mL, 69.5 and 315 ng/mL, respectively, p<0.05). Treatment
      exposures were similar. CONCLUSION: Numerous serum cytokines are elevated in
      Gaucher disease. CCL18/PARC, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL5/RANTES and
      CXCL8/IL-8 are potential biomarkers of osteonecrosis and may allow prediction of
      this disabling complication.

PMID- 21075652
TI  - A rapid computational filter for predicting the rate of human renal clearance.
AB  - In silico models that predict the rate of human renal clearance for a diverse set
      of drugs, that exhibit both active secretion and net re-absorption, have been
      produced using three statistical approaches. Partial Least Squares (PLS) and
      Random Forests (RF) have been used to produce continuous models whereas
      Classification And Regression Trees (CART) has only been used for a
      classification model. The best models generated from either PLS or RF produce
      significant models that can predict acids/zwitterions, bases and neutrals with
      approximate average fold errors of 3, 3 and 4, respectively, for an independent
      test set that covers oral drug-like property space. These models contain
      additional information on top of any influence arising from plasma protein
      binding on the rate of renal clearance. Classification And Regression Trees
      (CART) has been used to generate a classification tree leading to a simple set of
      Renal Clearance Rules (RCR) that can be applied to man. The rules are influenced
      by lipophilicity and ion class and can correctly predict 60% of an independent
      test set. These percentages increase to 71% and 79% for drugs with renal
      clearances of < 0.1 ml/min/kg and > 1 ml/min/kg, respectively. As far as the
      authors are aware these are the first set of models to appear in the literature
      that predict the rate of human renal clearance and can be used to manipulate
      molecular properties leading to new drugs that are less likely to fail due to
      renal clearance.

PMID- 21075654
TI  - GLP-1: what is known, new and controversial in 2010?
AB  - Over the past 2 years, more than 1300 manuscripts have been published on glucagon
      like peptide-1 (GLP-1) and yet, what do we know about it for sure? The European
      Club for the Study of GLP-1 (EuCSGLP-1) has debated the latest controversies
      concerning GLP-1, including both fundamental and clinical aspects, and concluded
      that the control of glucose metabolism by GLP-1 requires paracrine activation of
      the enteric nervous system to regulate numerous physiological functions. This
      involves-but is not limited to-the endocrine pancreas, liver, cardiovascular
      system, gastric-emptying and the brain. For this reason, the role of GLP-1 as an
      endocrine hormone has come under question. As systemic concentration of the
      peptide was not thought to be relevant to its physiological action, it was
      proposed that dipeptidyl peptidase-4 (DPP4) inhibitors would involve the control
      of enteric, rather than circulating, DPP4 activity to effectively regulate
      glycaemia. In any case, the concomitant insulinotropic and glucagonostatic roles
      of GLP-1 were believed to be of equal importance to glucose control. Another
      important question was related to the role of GLP-1 on beta cell apoptosis,
      regeneration and differentiation in type 2 diabetic patients. Although evidence
      in vitro showed that GLP-1 controls these functions, such effects remain elusive
      in humans in vivo. Nevertheless, the consensus was that GLP-1 could control
      glucose responsiveness, one of the first impaired physiological functions at the
      onset of diabetes. The therapeutic efficiency of GLP-1 would be related to the
      initial restoration of glucose competence, while an increase of beta cell mass
      has not yet been demonstrated. From a clinical and fundamental point of view, it
      was concluded that, at the onset of diabetes, an initial triggering of GLP-1
      secretion-by metformin coupled with a DPP4 inhibitor-would help to activate the
      gut-peripheral axis and, hence, restore adequate regulation of glycaemia. GLP-1
      analogues would certainly be helpful in association with long-acting insulin
      (albeit off-label) in patients with impaired beta cells and GLP-1 secretory
      potential. However, a reliable and routine feasible test to systematically assess
      dynamic insulin secretion is essential. More important, factors that influence
      therapeutic response, such as compliance and lifestyle, as well as
      pharmacokinetics and dosing, disease duration, age, gender, ethnicity, patients'
      clinical characteristics, autonomic nervous system integrity and genotype
      characteristics also need to be considered. A few innovative perspectives have
      been debated, such as the recently discovered cardiovascular protective effects
      of the native GLP-1 peptide and its degradation product GLP-1(9-36), as well as
      the neuroprotection offered by GLP-1. Although still considered speculative,
      these perspectives remain hopeful and promising.

PMID- 21075653
TI  - The binding modes and binding affinities of epipodophyllotoxin derivatives with
      human topoisomerase IIalpha.
AB  - Epipodophyllotoxin derivatives have important therapeutic value in the treatment
      of human cancers. These drugs kill cells by inhibiting the ability of
      topoisomerase II (TP II) to ligate nucleic acids that it cleaves during the
      double-stranded DNA passage reaction. The 3D structure of human TP IIalpha was
      modeled by homology modeling. A virtual library consisting of 143
      epipodophyllotoxin derivatives has been developed. Their molecular interactions
      and binding affinities with modeled human TP IIalpha have been studied using the
      docking and Bimolecular Association with Energetics (eMBrAcE) developed by
      Schrodinger. Structure activity relationship models were developed between the
      experimental activity expressed in terms of percentage of intracellular covalent
      TP II-DNA complexes (log PCPDCF) of these compounds and molecular descriptors
      like docking score and free energy of binding. For both the cases the r2 was in
      the range of 0.624-0.800 indicating good data fit and r2(cv) was in the range of
      0.606-774 indicating that the predictive capabilities of the models were
      acceptable. Low levels of root mean square error for the majority of inhibitors
      establish the docking and eMBrAcE based prediction model as an efficient tool for
      generating more potent and specific inhibitors of human TP IIalpha by testing
      rationally designed lead compounds based on epipodophyllotoxin derivatization.

PMID- 21075655
TI  - [Vascularized bone transfer of scapula apophysis].
AB  - The vascularized bone transfer of the scapular apophysis was described for the
      first time by Gilbert and Teot (1982) [1]. The growing pattern of this specific
      apophysis has large capacity and the plasticity during remodeling is unique.
      Primarily used for mandibular reconstruction, the scapular crest is also suitable
      for humeral or femoral reconstruction as well as for carpal stabilization in
      radial hand malformation, which is considered to be the main clinical indication.
      The radial hand malformation is characterized by an insufficient ulnar carpal
      stabilization which leads to luxation and radial deviation of the carpus. Using
      the vascularized scapular transfer in volar apposition to the ulnar, it enables
      enlarging the contact surface area with the carpus, thus stabilizing the wrist.
      Due to the preserved epiphyseal vascularization, good remodeling and integration
      of the scapular crest is achieved until consolidation takes place.

PMID- 21075656
TI  - [Free vascularized bone transfer en bout de chaine].
AB  - The vascularized bone proved its capacity to be healed, without resorption even
      in sclerotic or infected tissue. Reconstruction of the distal part of the finger
      is often difficult for a pedicle transplant and a conventional bone transplant
      disappears. So the free vascularized bone transfer (FVBT) is indicated in distal
      post-traumatic finger amputations. According to the loss of substance to be
      reconstructed, the vascularised bone is harvested with some pulp, the nail
      complex or the cartilage of growth for a child. We report our experience of the
      technique of wrap around modified, of partial transfers of the second toe and the
      technique of reconstruction of claw nail deformity. The vascularised transfer of
      the cartilage of growth at the child is essential to allow the growth of the
      transferred phalanx. The indications are rare, however the children, the
      musicians or the patients who require fine pinch can benefit from this type of
      sophisticated reconstructive microsurgery.

PMID- 21075657
TI  - [The vascularized articular transfers from the foot].
AB  - Complete destruction of the PIP or MCP joint space can be treated by a
      vascularized transfer from the foot in selected patients. The surgical technique
      for PIP and MTP vascularised transplantation is described with special emphasis
      on recent improvements (use of a short vascular pedicle, refinements in donor
      site reconstruction). Results of a series of 50 transfers performed between 1992
      and 2009 are presented. PIP transfer was performed in 37 patients, at an average
      age of 18.3 years (range 3 to 40) leading to an average active ROM of 44 degrees 
      (0-80), with a lag of extension of 34.2 degrees  (0-80). MCP transfer was
      performed in 12 patients (13 transfers), at an average age of 21.3 years (range 3
      to 40) leading to an average range of motion of 60 degrees  (35-80), with a lag
      of extension of 18.6 degrees  (0-30). None of the reconstructed articulations was
      painful. On the plain radiographs, no degradation of the joint space of the
      transferred articulations was noted. Within the pediatric population, the growth
      potential was preserved, signing the perenniality of the vascularization of the
      transfers. When faced to a complete joint destruction involving either the PIP or
      the MCP of the long fingers, reconstruction can be achieved by the mean of a
      vascularized joint transfer. The range of motion obtained with these transfers is
      not superior to what is observed after arthroplasty but it will persist with
      time. Therefore, even it is a technically demanding option, it should remain in
      our armamentarium as an alternative to joint fusion or joint arthroplasty.

PMID- 21075658
TI  - [Radiocarpal reconstruction by island transfer of the distal radio-ulnar joint].
AB  - INTRODUCTION: We described the island transfer of the DRUJ to reconstruct the
      radiocarpal joint when the radiocarpal and the mediocarpal joints are destroyed.
      The objective is to avoid wrist arthrodesis or prosthesis. PATIENTS AND METHOD:
      From 1993 to 1997, five patients were operated, five men, the average age was 55
      years (36 to 67). The operated side was the dominant side one time. The joint
      destruction was secondary to: SLAC wrist (stage 3) in two cases, a failure of PRC
      in two cases and post-traumatic necrosis of the lunatum in one case. RESULTS: One
      failure was resumed by total wrist arthrodesis at 1-year follow-up. Four patients
      were revised with 11 years follow-up (from nine to 13). Two patients presented a
      pain-free wrist, two patients complain of barometric pain or after heavy works.
      The average mobility was: extension 40 degrees , flexion 25 degrees , ulnar
      deviation 30 degrees , radial deviation -3 degrees , complete pronosupination.
      The strength was 65% of the opposite side. X-rays showed an important radiocarpal
      reshaping and ulnar sliding of the carpus. DISCUSSION: The island transfer of the
      DRUJ was possible in every case. The discordance between clinical and
      radiological results can be explained by joint denervation. We stopped this
      procedure not to sacrifice any more the healthy DRUJ. CONCLUSION: The island
      transfer of the DRUJ to reconstruct the radiocarpal joint is a solution to avoid
      total wrist arthrodesis or prosthesis if we accept the DRUJ sacrifice.

PMID- 21075659
TI  - [Simple and composite ulnar island bone transfers in hand reconstructive
      surgery].
AB  - Over several years, the author has devised different techniques for difficult
      bony reconstruction in hand surgery. It is based on compound island transfers of
      ulnar origin, harvested from the forearm's lower third with reverses flow
      vascularization. Because of the variety of arterial ramifications, these
      transplants can consist, either of a simple bone ulnar fragment or when
      associated, of compound cutaneous-osseous, or even cutaneous-tendineous-osseous
      transplants. These transplants based on a clinical experience of 49 cases can be
      used by retrograde rotation for a variety of indications such a recalcitrant
      nonunion of the scaphoid bone, Kienbock disease, osteochondroma with fracture, or
      severe post-traumatic sequellae. These procedures performed in one operating time
      permit reconstruction by using vascularized bone and offer large potential
      solutions improving bone healing.

PMID- 21075660
TI  - [Vascularized periosteum and bone regeneration].
AB  - The osteogenic potential of periosteum is widely recognized. During development,
      it plays a prominent role in the radial growth of long bones. Similarly, it has a
      key role in the consolidation of fractures. The physiological function of
      periosteum in the healthy, mature skeleton remains relatively subtle; however,
      its detachment from the bone surface reactivates its potential for fibrogenic and
      osteochondrogenic regeneration. This discreet anatomical structure is actually a
      reservoir of mesenchymal progenitor cells capable of proliferating and
      differentiating, by reinitializing cellular and molecular cascades of
      embryogenesis in mesenchymal tissues. However, given the hitherto limited
      knowledge of the quantitative potential of periosteum and of the pathways
      regulating tissue differentiation during regeneration, human applications have
      remained anecdotal. The findings of several in vivo and in vitro experiments
      indicate that the maintenance of the periosteum's vascularization stimulates its
      quantitative potential. The structural organization of the regenerated material
      in vivo is governed by locoregional biological and mechanical regulatory
      mechanisms that serve to make it capable of performing its new functions. The
      increasing awareness of periosteum's potential is stimulating active research in
      the fields of cellular biology and tissue engineering. The demonstration of its
      regenerative potential in animals gives reason to believe that strips of
      vascularized periosteum could become part of the developing armamentarium of
      regenerative medicine.

PMID- 21075661
TI  - [Osseous vascular anatomy in the hand and wrist].
AB  - The design and the realization of vascularized osseous grafts at the hand and the
      wrist require a precise knowledge of the general and regional anatomy. This
      article gives first a progress report on current knowledge about the general
      organization of arterial and venous vascularization, of the long bones (number
      and localization of the nutrient foramina, communication between the epiphyseo
      metaphyseal and diaphyseal networks) and of the short bones, in the adult and the
      child, before the closing of the growth plate. The general organization of
      arterial vascularization of the hand and the wrist is pointed out, with the
      current nomenclature and the contribution of the recent publications, in
      particular in these, which relate to the distal extremity of the radius. The
      vascularization of each bone (radius and ulna, carpal bones, metacarpals and
      phalanges) is then described; making way, the anatomical bases of each
      vascularized bone graft, which can be harvested there, are described. The last
      technical projections are included, in particular the realization of the reverse
      flow vascularized bone grafts harvested from the metacarpals. This article still
      gives a progress report on the osseous vascularization of the short bones, in
      particular of those which are exposed the most to the osteonecrosis (scaphoid,
      lunatum). It has the ambition to light the reader and to prepare him (her) with
      the reading of the following chapters.

PMID- 21075662
TI  - [Bone quality evaluation in allograft hand transplant].
AB  - Five bilateral forearms allograft have been performed between January 2000 and
      July 2009 in Lyon (France). The first four patients (three males, one female)
      have been the subject of an assessment of the bone quality of those allografts.
      The techniques selected for this study were: radioclinical analysis, bone
      scintigraphy, MRI, bone densitometry and High Resolution peripheral Quantitative
      Computed Tomography (HR-PQCT). Histology has been performed only on the first
      patient unilaterally grafted in 1998 who did not take part in this clinical
      research protocol, after amputation of his rejected graft. On the clinical,
      radiological and scintigraphical aspects, donor bone integration in hands
      allograft are good on a macroscopic point of view considering the healing and the
      general reaction of the bone in situation of fractures, infection and growth. The
      scintigraphy does not show important variations compared to the ones we can
      observe on contact with osteosynthesis material or during bone autografts. MRI
      found neither focal nor periosteal anomaly on grafted bone. The bone densitometry
      did not show significant difference with secondary osteoporosis one can observe
      in other grafted patients under immunosuppressive treatment. The HR-PQCT showed
      for the three males patients, a higher loss in volumetric density, for grafted
      bone than in the recipient patient control skeleton. Due to the few patients of
      this series, and the discrepancies in follow-up duration, the presented data have
      to be confirmed with further studies.

PMID- 21075663
TI  - [Past, present and future of vascularised bone transfers in the hand and wrist].
AB  - The author specifies the aims and indications for simple or compound pedicle or
      free vascularised bone and bone and joint grafts (VBGs and VBJGs). He relates the
      history of VBGs whose indications for the wrist are often many and varied for the
      treatment of scaphoid non-union and Kienboch's disease. Within the hand the
      indication for compound VBGs is dominated by thumb reconstruction (skin and bone
      grafts). Compound VBGs and VBJGs used in an emergency for hand trauma, harvested
      from another irrecoverable long finger (bank finger) are extremely varied and
      adapted to each particular case. For secondary joint reconstruction in the adult,
      VBJGs must be discussed along with prosthetic arthroplasties (radio-carpal, lower
      radio-ulnar, trapezo-metacarpal, interphalangeal). For children VBJGs with an
      included growth plate maintain their indication. The immediate future of VBGs is
      that of a better knowledge of bone necrosis and bone innervation as well as an
      improvement in surgical techniques: microsurgery and robotics, mini-invasive
      surgery (wrist arthroscopy). The near future for VBGs is to control bone
      consolidation thanks to progress in the bio-engineering of bone tissue, which may
      make them obsolete and, for VBJGs, vascularised joint allografts, thanks to
      progress in immunosuppressant treatments. Although the immediate future and this
      near future may be envisaged according to the current advances, the same is not
      true for the distant future which remains totally unforeseeable, although this
      might involve regeneration and construction of organs by man himself.

PMID- 21075664
TI  - [Vascularized pisiform transfer in place of lunatum for Kienbock's disease].
AB  - There is a specific vascularization of the pisiform bone depending on the cubito
      dorsal artery, branch of the ulnar artery. The vascularized pisiform bone may be
      transferred in place of the excised lunatum. The aims are to decrease pain when
      keeping the mobility, to replace a dead bone, to maintain the distance between
      scaphoid and triquetrum and radius and capitatum, by preventing the carpal
      collapse. X-rays and a MRI are performed. The vascularized transfer is indicated
      at stage III of the usual classifications. The technique is described, insisting
      on the transferred bone stabilization using ligament reconstructions. Radial
      shortening or scapho-capitate limited arthrodesis may be combined to reduce the
      stress on the transferred bone. Fifty-one cases have been performed at stage IIIa
      or IIIb and sometimes IV of the disease. The maximum follow-up is 15 years. The
      pain has decreased constantly. Motion in flexion-extension has an increase of
      more than 35 degrees , radial and ulnar deviation of more than 14 degrees .
      Strength has been slightly modified to more than 10%. The complications are: one
      case of "complex regional pain syndrome", one infection reoperated and one
      infection cured by antibiotics; one reoperation for a proximal row carpectomy.
      Results of this technique have been published in the literature. This technique
      provides regularly good results with a long follow-up. A precise technique is
      mandatory.

PMID- 21075665
TI  - [Results of the treatment of basal thumb osteoarthritis by Rubis II prosthesis
      after more than 5 years. A retrospective study of 118 cases].
AB  - OBJECTIVES: The goal of the work was to evaluate the mid-term results of the
      Rubis II(r) trapeziometacarpal prosthesis for the treatment of basal thumb
      osteoarthritis. METHODS: From 1997 to 2003, 118 trapeziometacarpal prostheses
      Rubis II(r) were implanted at Saint-Quentin's Hospital. Seventy-seven have been
      clinically and radiologically reviewed. The average follow-up was of 88 months.
      Sixteen patients were reviewed by phone. Fourteen patients were lost to contact
      and two died (13.5% of cases). Nine prostheses were removed (7.6% of cases).
      RESULTS: Among the reviewed prostheses, 76.6% of patients had no pain, the others
      had moderate pain. Postoperatively, the average opposition according to
      Kapandji's scale was 9.52. The average key-pinch force was similar on both sides.
      All reviewed patients were satisfied or very satisfied. No radiological loosening
      was noted. Nine removals were necessary; for post-traumatic dislocation in six
      cases, post-traumatic fracture of the trapezium in two cases, and inflammatory
      reaction with no infection in one case. The survival rate of the prosthesis was
      93% at five years. CONCLUSIONS: The Rubis II(r) prosthesis presents a
      satisfactory survival rate after five years and good clinical results. The design
      of the implant could explain the absence of loosening. The main risk of the Rubis
      II prosthesis seems to be the post-traumatic dislocation occurring mostly during
      the first two years after surgery.

PMID- 21075667
TI  - [The role of imaging in the assessment of vascularity at hand and wrist].
AB  - The viability of the bone is compromised in two main situations at the wrist:
      Kienbock's disease and scaphoid nonunion with avascular necrosis. Plain
      radiography and CT allow an accurate anatomical approach of morphological changes
      associated with avascular necrosis of the lunate and the scaphoid fracture with
      complications. CT is readily available to detect nondisplaced fractures. However,
      early forms of necrosis can be misdiagnosed and evaluation of bone vitality is
      impossible. MRI is the best imaging modality to detect avascular necrosis and the
      intravenous injection of gadolinium improves the specificity of diagnosis of
      necrosis. The lack of enhancement of the proximal fragment of the scaphoid leads
      the surgeon to use a vascular graft in the treatment of nonunion. The technique
      has its limitations. The bone necrosis is histologically complex and contrast
      enhancement does not mean necessarily viability. However, MRI is still the most
      powerful imaging modality in the assessment of the bone marrow.

PMID- 21075666
TI  - [Early stages of trapezo-metacarpal joint arthritis and rotatory island transfer
      of the trapezo-metacarpal joint. DOOR procedure].
AB  - INTRODUCTION: Trapezium dysplasia and trapezo-metacarpal joint instability induce
      TMC-joint arthritis. To correct these two factors, we propose a surgical
      technique associating a double oblique osteotomy of the trapezium and of the
      first metacarpal basis, and an island rotator transfer of the TMC-joint harvested
      in block on the radial pedicle. The articular block is rotated at 180 degrees  on
      the longitudinal axis of the thumb. METHOD: Since 2000, 41 cases were performed
      on 38 patients (35 women, three men). Mean age was 47 (from 17 to 63). All the
      patients complained of a painful thumb and sometimes of instability. The mobility
      was preserved (Kapandji 9/3). The grasp was 43% of the opposite side. X-rays
      showed a TMC-joint instability in all the cases. RESULTS: DOOR procedure was
      possible 41 times. With a mean follow-up of 65 months (from three months to ten
      years), 28 thumbs are pain-free, nine patients complain of barometric pain or
      pain after heavy works. Four thumbs were reoperated after failure of the
      procedure. Mobility decreased (Kapandji 8/2), the grasp increased to 100% of the
      opposite side. The joint was stabilized in all the cases. X-rays showed an
      osteolysis in three cases. The cartilage was worse in 19 cases, improved in five
      cases, stable in 14 cases. DISCUSSION: DOOR procedure is a very demanding
      procedure but reliable. The correction of the dysplasia is constant. Denervation
      could explain the good clinical results in cases of joint narrowing. CONCLUSION:
      DOOR procedure is a solution in cases of trapezium dysplasia associated with
      instability and early stages of osteoarthritis in young women.

PMID- 21075668
TI  - Drug-eluting stents for coronary artery disease: a review.
AB  - Over the past decade the introduction of drug-eluting stents (DESs) has
      revolutionised the treatment of coronary artery disease. However, in recent years
      concern has arisen over the long-term safety and efficacy of DESs due to the
      occurrence of late adverse clinical events such as stent thrombosis. With this
      concern in mind, research and development is currently centred on increasing the
      long-term safety and efficacy of DESs. The aim of this paper is to provide a
      thorough review of currently approved and promising investigational DESs. With
      dozens of companies involved in the development of new and innovative anti
      restenotic agents, polymeric coatings and stent platforms, it is intended that
      this review paper will provide a clear indication of how DESs are currently
      evolving and prove a valuable reference tool for future research in this area.

PMID- 21075671
TI  - RT3 accelerometer shoulder activity: discrimination of activity levels by the RT3
      accelerometer for the assessment of shoulder physical activity (SPA).
AB  - We investigated whether the RT3 accelerometer can be used to discriminate and
      characterize the different levels of shoulder physical activity (SPA) in both
      patients and healthy adults. Twenty healthy adults and 20 patients with shoulder
      disorders (SDs) performed activities at 5 levels of difficulty (easy, easy
      moderate, moderate, hard-moderate, hard) with the same RT3 accelerometer fixed on
      the arm. The Vector Magnitude (VM) is the square root of the sum of squares from
      each axis to determine the overall magnitude of activity. The SPA counts of
      healthy group were significantly higher than the patient group in every level
      except easy (31-38 VM counts difference, p < 0.01). For both groups, the hard
      task demonstrated higher counts as compared to the other tasks. The easy task
      showed lower counts as compared to the other tasks. In the patient group,
      significant correlation between FLEX-SF scores and counts from the RT3 (R = 
      0.72, p < 0.05) was found in the moderate tasks. The results of this study showed
      that RT3 can be a potential measurement tool to (1) characterize the difference
      of SPA between two groups; and (2) partially discriminate the different levels of
      SPA. The correlations between self-reported function scores and SPA RT3 counts
      are dependent on self-reported task difficulty.

PMID- 21075670
TI  - Childhood obesity and proximity to urban parks and recreational resources: a
      longitudinal cohort study.
AB  - The objective of the research was to assess how proximity to parks and
      recreational resources affects the development of childhood obesity through a
      longitudinal study. Data were collected on 3173 children aged 9-10 from 12
      communities in Southern California in 1993 and 1996. Children were followed for
      eight years to collect longitudinal information, including objectively measured
      body mass index (BMI). Multilevel growth curve models were used to assess
      associations between attained BMI growth at age 18 and numerous environmental
      variables, including park space and recreational program access. For park acres
      within a 500 m distance of children's homes, there were significant inverse
      associations with attained BMI at age 18. Effect sizes were larger for boys than
      for girls. Recreation programs within a 10 km buffer of children's homes were
      significantly and inversely associated with achieved levels in BMI at age 18,
      with effect sizes for boys also larger than those for girls. We conclude that
      children with better access to parks and recreational resources are less likely
      to experience significant increases in attained BMI.

PMID- 21075673
TI  - Chemical mutagenesis: selective post-expression interconversion of protein amino
      acid residues.
AB  - The ability to alter protein structure by site-directed mutagenesis has
      revolutionized biochemical research. Controlled mutations at the DNA level,
      before protein translation, are now routine. These techniques allow specific,
      high fidelity interconversion largely between 20 natural, proteinogenic amino
      acids. Nonetheless, there is a need to incorporate other amino acids, both
      natural and unnatural, that are not accessible using standard site-directed
      mutagenesis and expression systems. Post-translational chemistry offers access to
      these side chains. Nearly half a century ago, the idea of a 'chemical mutation'
      was proposed and the interconversion between amino acid side chains was
      demonstrated on select proteins. In these isolated examples, a powerful proof-of
      concept was demonstrated. Here, we revive the idea of chemical mutagenesis and
      discuss the prospect of its general application in protein science. In
      particular, we consider amino acids that are chemical precursors to a functional
      set of other side chains. Among these, dehydroalanine has much potential. There
      are multiple methods available for dehydroalanine incorporation into proteins and
      this residue is an acceptor for a variety of nucleophiles. When used in
      conjunction with standard genetic techniques, chemical mutagenesis may allow
      access to natural, modified, and unnatural amino residues on translated, folded
      proteins.

PMID- 21075672
TI  - Nonrigid registration of dynamic medical imaging data using nD + t B-splines and
      a groupwise optimization approach.
AB  - A registration method for motion estimation in dynamic medical imaging data is
      proposed. Registration is performed directly on the dynamic image, thus avoiding
      a bias towards a specifically chosen reference time point. Both spatial and
      temporal smoothness of the transformations are taken into account. Optionally,
      cyclic motion can be imposed, which can be useful for visualization (viewing the
      segmentation sequentially) or model building purposes. The method is based on a
      3D (2D+time) or 4D (3D+time) free-form B-spline deformation model, a similarity
      metric that minimizes the intensity variances over time and constrained
      optimization using a stochastic gradient descent method with adaptive step size
      estimation. The method was quantitatively compared with existing registration
      techniques on synthetic data and 3D+t computed tomography data of the lungs. This
      showed subvoxel accuracy while delivering smooth transformations, and high
      consistency of the registration results. Furthermore, the accuracy of semi
      automatic derivation of left ventricular volume curves from 3D+t computed
      tomography angiography data of the heart was evaluated. On average, the deviation
      from the curves derived from the manual annotations was approximately 3%. The
      potential of the method for other imaging modalities was shown on 2D+t ultrasound
      and 2D+t magnetic resonance images. The software is publicly available as an
      extension to the registration package elastix.

PMID- 21075669
TI  - The use of computational fluid dynamics in the development of ventricular assist
      devices.
AB  - Progress in the field of prosthetic cardiovascular devices has significantly
      contributed to the rapid advancements in cardiac therapy during the last four
      decades. The concept of mechanical circulatory assistance was established with
      the first successful clinical use of heart-lung machines for cardiopulmonary
      bypass. Since then a variety of devices have been developed to replace or assist
      diseased components of the cardiovascular system. Ventricular assist devices
      (VADs) are basically mechanical pumps designed to augment or replace the function
      of one or more chambers of the failing heart. Computational Fluid Dynamics (CFD)
      is an attractive tool in the development process of VADs, allowing numerous
      different designs to be characterized for their functional performance virtually,
      for a wide range of operating conditions, without the physical device being
      fabricated. However, VADs operate in a flow regime which is traditionally
      difficult to simulate; the transitional region at the boundary of laminar and
      turbulent flow. Hence different methods have been used and the best approach is
      debatable. In addition to these fundamental fluid dynamic issues, blood consists
      of biological cells. Device-induced biological complications are a serious
      consequence of VAD use. The complications include blood damage (haemolysis, blood
      cell activation), thrombosis and emboli. Patients are required to take
      anticoagulation medication constantly which may cause bleeding. Despite many
      efforts blood damage models have still not been implemented satisfactorily into
      numerical analysis of VADs, which severely undermines the full potential of CFD.
      This paper reviews the current state of the art CFD for analysis of blood pumps,
      including a practical critical review of the studies to date, which should help
      device designers choose the most appropriate methods; a summary of blood damage
      models and the difficulties in implementing them into CFD; and current gaps in
      knowledge and areas for future work.

PMID- 21075675
TI  - Determining the privacy policy deficiencies of health ICT applications through
      semi-formal modelling.
AB  - To ensure that patient confidentiality is securely maintained, health ICT
      applications that contain sensitive personal information demand comprehensive
      privacy policies. Determining the adequacy of these policies to meet legal
      conformity together with clinical users and patient expectation is demanding in
      practice. Organisations and agencies looking to analyse their Privacy and
      Security policies can benefit from guidance provided by outside entities such as
      the Privacy Office of their State or Government together with law firms and ICT
      specialists. The advice given is not uniform and often open to different
      interpretations. Of greater concern is the possibility of overlooking any
      important aspects that later result in a data breach. Based on three case
      studies, this paper considers whether a more formal approach to privacy analysis
      could be taken that would help identify the full coverage of a Privacy Impact
      Analysis and determine the deficiencies with an organisation's current policies
      and approach. A diagrammatic model showing the relationships between
      Confidentiality, Privacy, Trust, Security and Safety is introduced. First the
      validity of this model is determined by mapping it against the real-world case
      studies taken from three healthcare services that depend on ICT. Then, by using
      software engineering methods, a formal mapping of the relationships is undertaken
      to identify a full set of policies needed to satisfy the model. How effective
      this approach may prove as a generic method for deriving a comprehensive set of
      policies in health ICT applications is finally discussed.

PMID- 21075674
TI  - Spin-Hamiltonian parameters and defect structure for the rhombic Dy3+ center in
      AgCl crystal.
AB  - Based on the defect model that the rhombic Dy(3+) center in AgCl crystal is
      formed by substitutional Dy3+ ion associated with two nearest Ag+ vacancies (VAg)
      along the <110> and <110> axes owing to charge compensation, the spin-Hamiltonian
      parameters (g factors gi and hyperfine structure constants 161Ai and 163Ai, where
      i=x, y, z) of this rhombic Dy3+ center are calculated from a diagonalization (of
      energy matrix) method. In the method, the Zeeman (or magnetic) and hyperfine
      interaction terms are attached to the classical Hamiltonian used in the
      calculation of crystal-field energy levels and a 66*66 energy matrix concerning
      this Hamiltonian is constructed by taking all the ground-term multiplets 6HJ
      (J=15/2, 13/2, 11/2, 9/2, 7/2, 5/2) into account. The calculated results (g
      factors gi and average |A(161Dy3+)| and |A(163Dy3+)|) are in reasonable agreement
      with the experimental values. From the calculations, the above defect model of
      rhombic Dy3+ center is confirmed, the defect structure of this Dy3+ center
      (characterized by the displacement of Cl- ligand caused by VAg) is obtained and
      the components of hyperfine structure constants Ai(161Dy3+) and Ai(163Dy3+) are
      predicted. The results are discussed.

PMID- 21075676
TI  - A methodology for the pseudonymization of medical data.
AB  - PURPOSE: E-health enables the sharing of patient-related data whenever and
      wherever necessary. Electronic health records (EHRs) promise to improve
      communication between health care providers, thus leading to better quality of
      patients' treatment and reduced costs. However, as highly sensitive patient
      information provides a promising goal for attackers and is also frequently
      demanded by insurance companies and employers, there is increasing social and
      political pressure regarding the prevention of health data misuse. This work
      addresses this problem and introduces a methodology that protects health records
      from unauthorized access and lets the patient as data owner decide who the
      authorized persons are, i.e., who the patient discloses her health information
      to. Therefore, the methodology prevents data disclosure that negatively
      influences the patient's life (e.g., by being denied health insurance or
      employment). METHODS: This research uses a combination of conceptual-analytical,
      artifact-building and artifact-evaluating research approaches. The article starts
      with a detailed exploration of existing privacy protection mechanisms, such as
      encryption, anonymization and pseudonymization, by comparing and analyzing
      related work (conceptual-analytical approach). Based on these results and the
      identified shortcomings, a pseudonymization methodology is defined and evaluated
      by means of a threat analysis. Finally, the research results are validated with
      the design and implementation of a prototype (artifact building and artifact
      evaluation). RESULTS: This paper presents a new methodology for the
      pseudonymization of medical data that stores health data decoupled from the
      corresponding patient-identifying information, allowing privacy-preserving
      secondary use of the health records in clinical studies without additional
      anonymization steps. In contrast to clinical studies, where it is not necessary
      to identify the individual participants, insurance companies and employers are
      interested in the health status of individuals such as potential insurance or job
      applicants. In this case, pseudonymized records are practically useless for these
      parties as the patient controls who is able to reestablish the link between
      health records and patient for primary use - usually only trusted health care
      providers. CONCLUSIONS: The framework provides health care providers with a
      unique solution that guarantees data privacy (e.g., according to HIPAA) and
      allows primary and secondary use of the data at the same time. The security
      analysis showed that the methodology is secure and protected against common
      intruder scenarios.

PMID- 21075677
TI  - The recommendations from the 2009 SiHIS working conference in Hiroshima--Issues
      on trustworthiness of health information and patient safety.
AB  - Held on 21st to 23rd November 2009 in Hiroshima, the SiHIS working conference
      aimed at finding solutions to approach to an idealistic society where (1) the
      individual can trust information with full understanding and responsibility, (2)
      the individual can allow the use of information backed by sound legitimated
      environment, (3) information can play its role for better healthcare and the
      improvement of medicine. The purpose of this paper is to propose recommendations
      from this working conference.

PMID- 21075678
TI  - Dobrava-Belgrade hantavirus infection mimics acute appendicitis.
AB  - Dobrava-Belgrade hantavirus infection mimicked acute appendicitis in a patient
      suffering from hemorrhagic fever with renal syndrome in Hungary. The 27-year-old
      man was admitted to the local hospital with severe abdominal pain localized
      mainly at the right lower quadrant of the abdomen and with fever, nausea,
      vomiting and bloody diarrhea. Based on these findings supported by computerized
      tomography acute perforated appendicitis was suspected and an explorative
      laparatomy was performed, which did not confirm the diagnosis. Next day he
      developed acute oliguric renal failure raising the possibility of hantavirus
      infection. Specific serum IgG and IgM antibodies against hantavirus were
      identified, and by molecular methods the presence of Dobrava-Belgrade virus was
      proven. This report describes a rare clinical manifestation of hemorrhagic fever
      with renal syndrome (HFRS), and shows that HFRS might be difficult to diagnose
      especially when symptoms mimick those of an acute abdominal inflammation.

PMID- 21075679
TI  - Singleplex real-time RT-PCR for detection of influenza A virus and simultaneous
      differentiation of A/H1N1v and evaluation of the RealStar influenza kit.
AB  - BACKGROUND: A novel influenza A virus, subtype A/H1N1v emerged in April 2009 and
      caused the first influenza pandemic of the 21st century. Reliable detection and
      differentiation from seasonal influenza viruses is mandatory for appropriate case
      management as well as public health. OBJECTIVES: To develop and technically
      validate a novel one-step real-time RT-PCR assay which can be used for influenza
      A virus screening and subtyping of A/H1N1v in a singleplex fashion. To assess the
      clinical performance of a novel commercial influenza RT-PCR kit based on the in
      house version. STUDY DESIGN: A real-time RT-PCR assay targeting the matrix gene
      of influenza A viruses was developed and validated using in vitro transcribed RNA
      derived from influenza A/H1N1v, A/H1N1 and A/H3N2 virus as well as plaque
      quantified influenza A/H1N1v, A/H1N1 and A/H3N2 virus samples. After validation
      of the in-house version the commercial RealStar kit was used to assess the
      clinical performance and specificity on a panel of influenza viruses including
      A/H1N1v, A/H1N1, swine A/H1N1, A/H3N2, avian A/H5N1 as well as patient specimens.
      RESULTS: The lower limit of detection of the in-house version was 2149, 1376 and
      2994 RNA copies/ml for A/H1N1v, A/H1N1 and A/H3N2, respectively. The RealStar kit
      displayed 100% sensitivity and specificity and could reliably discriminate
      influenza A viruses from A/H1N1v. No cross reaction with swine A/H1N1 and A/H1N2
      was observed with the RealStar A/H1N1v specific probe. CONCLUSION: Both assays
      demonstrated high sensitivity and specificity and might assist in the diagnosis
      of suspected influenza cases.

PMID- 21075680
TI  - Wavelet based algorithm for the estimation of frequency flow from
      electroencephalogram data during epileptic seizure.
AB  - OBJECTIVE: EEG data during temporal lobe seizures have been reported to show
      lateralized buildup of theta activity. However the exact dynamics of the theta
      activity and its clinical significance are not known. In this work we present an
      approach using wavelets to study the frequency flow dynamics of this buildup.
      METHODS: We employ continuous wavelet transform to obtain a time frequency
      representation of the EEG signal. Using a ridge extraction algorithm, the
      instantaneous frequency is estimated from the normalized scalogram. RESULT: We
      found that prior to the seizure onset, frequency flow builds up to 5-12 Hz range
      and the duration for which the frequency remains in this range gradually
      increases soon after the seizure onset. We also observed buildup at the adjacent
      regions. Such buildup characteristics are not seen during baseline conditions of
      the same patients. CONCLUSIONS: Simultaneous buildup of frequency at the temporal
      and the adjacent regions indicates that during seizure the neuronal interactions
      propagate over large regions of the brain. SIGNIFICANCE: Given that activity in
      the 5-12 Hz frequency range is seen often in the more alert state, our findings
      suggest that the brain might be in a transient alert state prior to the epileptic
      seizure.

PMID- 21075681
TI  - Effect of a serotonin antagonist on delay in grip muscle relaxation for persons
      with chronic hemiparetic stroke.
AB  - OBJECTIVE: To investigate if, following stroke, sustained involuntary activity
      after voluntary contraction (e.g., grip) of the long finger flexor muscles of the
      paretic hand is attributable to augmented serotonin release from brainstem
      pathways, affecting excitability of spastic motoneurons. METHODS: This single
      dose placebo-controlled study examined whether a serotonin receptor (5-HT2)
      antagonist, cyproheptadine hydrochloride, could reduce delay in muscle relaxation
      of a key paretic long finger flexor muscle immediately after grip for persons
      with stroke. Time to initiate the long finger flexor muscle contraction, grip and
      pinch strengths, and clinical hand function scores (the Action Research Arm Test
      and the Box and Block Test) were also assessed. RESULTS: Cyproheptadine
      hydrochloride reduced mean delays in finger relaxation (n=13; from 7.2 to 4.1 s;
      SEM=1.2 s; p=.026) in comparison to placebo, while leaving grip and pinch
      strengths and time to initiate the muscle contraction largely unaffected.
      Reduction in the relaxation time alone did not lead to increased clinical hand
      function scores. CONCLUSIONS: The findings support the supposition that
      monoaminergic brainstem pathways may be disinhibited following stroke, thereby
      resulting in increased delays in muscle relaxation. SIGNIFICANCE: Treatments to
      reduce delay in muscle relaxation may facilitate hand rehabilitation in persons
      with stroke.

PMID- 21075682
TI  - Altered dopamine modulation of LTD-like plasticity in Alzheimer's disease
      patients.
AB  - OBJECTIVE: Mechanisms of synaptic plasticity like long term depression (LTD) are
      altered in experimental models of Alzheimer's disease (AD). LTD-like plasticity
      mechanisms has not been yet fully investigated in AD patients. METHODS: Here we
      studied the effects of low frequency (1 Hz) repetitive transcranial magnetic
      stimulation (rTMS) over the primary motor cortex in a group of patients with a
      diagnosis of probable AD, compared to healthy age-matched controls (HS).
      Moreover, we tested the effects of a single dose of orally administered L-dopa,
      one of the key neurotransmitters in modulating synaptic plasticity mechanisms, on
      rTMS induced plasticity. RESULTS: We found that in AD patients the 1 Hz rTMS
      protocol did not induce the expected inhibitory effect, while a long lasting
      inhibition of MEP was observed in HS. In addition, L-dopa induced a clear form of
      reversal of the direction of plasticity in HS that was not evident in AD.
      CONCLUSIONS: Dopamine modulation of LTD-like plasticity is impaired when tested
      in AD patients. SIGNIFICANCE: These findings provide evidence of possible
      dysfunction of dopaminergic transmission in AD patients.

PMID- 21075683
TI  - The Australian and New Zealand cardiac pacing and implantable cardioverter
      defibrillator survey: calendar year 2009.
AB  - BACKGROUND: A pacemaker (PM) and Implantable Cardioverter-Defibrillator (ICD)
      Survey was undertaken in Australia and New Zealand for the calendar year 2009.
      RESULTS AND CONCLUSIONS: For 2009, the number of new implants for Australia was
      12,523 (11,850 in 2005) and 1277 for New Zealand (1134 in 2005). The number of
      new PM implants per million population was 565 for Australia (590 in 2005) and
      299 for New Zealand (275 in 2005). Both countries had substantial increases in PM
      replacements. There were 446 biventricular PMs implanted in Australia (461 in
      2005) and 45 in New Zealand (16 in 2005). Pulse generator types were
      predominantly dual chamber with 71% for Australia (72% in 2005) and 54% for New
      Zealand (51% in 2005). Transvenous pacing leads were overwhelmingly bipolar with
      marked increases in the use of active fixation leads; Australia 80% atrium, 75%
      ventricle and New Zealand 65% atrium, 62% ventricle. There was also a marked
      increase in the number of new ICDs implanted; Australia 3555 (2864 in 2005) and
      New Zealand 329 (134 in 2005). The new ICD implants per million population were
      160 for Australia (142 in 2005) and 77 for New Zealand (33 in 2005). The usage of
      biventricular ICDs was 33% for Australia and 13% for New Zealand.

PMID- 21075684
TI  - Langerhans cells: not your average dendritic cell.

PMID- 21075685
TI  - Promoting self awareness in undergraduate nursing students in relation to their
      health status and personal behaviours.
AB  - The purpose of this article is to report the experience of facilitating,
      delivering and evaluating a health assessment workshop as part of Assessing and
      Promoting Health module on the Bachelor of Nursing Science (BNSc) General and
      Intellectual Disability programme. This module is delivered to 65 nursing
      students (40 general and 25 intellectual disability) undertaking the first year
      of the four year programme. The aim of the workshop is to promote health
      awareness among these undergraduate students. The objectives are to provide
      students with time to self assess their health knowledge and lifestyle practices.
      From this students' current health behaviours are discussed in conjunction with
      recommendations from the Department of Health and Children (DOHC) (2005).
      Students are then provided with an opportunity to assess the stresses they
      perceive in their own lives and this is followed by a relaxation session guided
      by the facilitators. The teaching methods focus mostly on active student
      participation, demonstration and experience sharing.

PMID- 21075686
TI  - Current debate on pathogen inactivation of platelet concentrates--to use or not
      to use?
AB  - It is an important goal in transfusion practice to improve the quality and safety
      of platelet transfusions. Accordingly, blood services have implemented several
      complimentary measures such as continual improvement in donor selection, donor
      testing, newer development in collection/processing, including the diversion of
      the first part of collection to reduce the potential risk of bacterial
      contamination and the use of various platelet additive solutions and reduction in
      donor exposures through production multiple doses by apheresis procedures.
      Unfortunately despite considerable improvement in blood components safety
      bacterial transmission by platelet transfusion remains the major microbial cause
      of morbidity and mortality in transfusion medicine. Currently two major
      interventions are in practice, in some establishments, to reduce bacterial
      transfusion by platelets: selective/full bacterial screening and pathogen
      inactivation. The later is also effective against most known and unknown emerging
      nucleic acid containing viruses, as well as, parasites. In addition it also
      reduces the side effect associated with leucocytes, making its implementation
      highly appealing. In recent years, two methods for pathogen
      inactivation/reduction (abbreviation used later in this paper PI) of platelet
      concentrates have become available. Pathogen inactivation was the original term
      for the technology, but as it is argued that the inactivation may not be
      complete, some authors prefer the term "pathogen reduction". Although PI of
      cellular blood components is considered to be a "dream solution" to the problem
      of transfusion-related transmission of infectious diseases, the implementation of
      these precautionary interventional methods is not yet universally approved. The
      aim of this paper is to discuss some of the key issues in the debate on
      implementation of PI methods for platelet concentrates.

PMID- 21075687
TI  - This last edition of Transfusion and Apheresis Science of 2010, is substantial,
      with 23 full-length articles.

PMID- 21075688
TI  - T-cryptantigen (TCA) activation in sever pneumonia complicated with multiple
      organ failure.
AB  - A 19-month-old boy presented RBC T-cryptantigen (TCA) activation with severe
      pneumonia complicated with abnormal coagulation. The boy received fresh frozen
      plasma before TCA activation was confirmed. He developed hemolysis and multiple
      organ failure. The hemolysis anemia was successfully treated with washed RBC
      transfusion. However, he had to use dialysis because of renal dysfunction. The
      case prompted an urgent call to screen RBC TCA-activation in selective pediatric
      patients.

PMID- 21075689
TI  - Emergency medical kits on board commercial aircraft: a comparative study.
AB  - BACKGROUND: In cases of critical medical situations on board commercial aircraft,
      access to emergency medical kits can be lifesaving. Thus, this comparative study
      investigated acute care medication and equipment supplied in emergency medical
      kits on board both low-cost carriers and full-service carriers. METHODS: Thirty
      two European airlines (sixteen low-cost carriers and sixteen full-service
      carriers) were asked to provide anonymous data on the contents of their emergency
      medical kits. All emergency medical equipment and medication carried on board
      were subject to a descriptive analysis with regards to International Civil
      Aviation Organization (ICAO) standards for emergency medical kits, as well as
      variation and differences between low-cost carriers and full-service carriers.
      RESULTS: A total of twelve airlines (seven full-service carriers and five low
      cost carriers) participated in this study. None complied with ICAO standards.
      Emergency medical kits from both full-service carriers and low-cost carriers
      exhibited a high degree of variability. Two European low-cost carriers were
      assessed as being insufficiently equipped for a medical emergency requiring acute
      care. CONCLUSIONS: This study demonstrates the high degree of variability in the
      contents of emergency medical kits. Additionally, some airlines were equipped
      insufficiently for a critical medical situation on board their aircraft. Frequent
      checks of national authorities and further evaluation of acute care equipment are
      required to prepare for potentially life-threatening critical conditions
      occurring in special environments, such as in airplane during flight.

PMID- 21075690
TI  - Development of gut-homing receptors on circulating B cells during infancy.
AB  - B cell gut-homing is mainly mediated by alpha4beta7, CCR9 and CCR10. We here
      studied the expression of these receptors on B cells from cord blood and from
      peripheral blood at 1, 4, 18 and 36 months of age in a prospective cohort of
      Swedish infants. The proportion of all B cells expressing alpha4beta7 as well as
      the fraction of CCR10+ B cells expressing alpha4beta7 was highest in early
      infancy. Nearly all naive B cells in all age groups expressed alpha4beta7,
      whereas the expression on class-switched B cells decreased with age. Moreover,
      the proportion of both IgA+ and IgG+ B cells expressing alpha4beta7, CCR9 and
      CCR10 were higher during the first months when compared to adults. In conclusion,
      the high fraction of circulating IgA+ and IgG+ B cells expressing CCR9 and CCR10
      in the first months of life indicates activation of naive B cells in the gut,
      coinciding with bacterial colonization.

PMID- 21075691
TI  - Identification of a novel linear epitope on EspA from enterohemorrhagic E. coli
      using a neutralizing and protective monoclonal antibody.
AB  - Enterohemorrhagic E. coli (EHEC) causes severe diseases in humans and animals via
      the production of Shiga toxins, and injection of effectors into epithelia using
      type III secretion system (TTSS). E. coli secreted protein A (EspA) forms the
      filamentous conduits of TTSS, which extends into the translocation pore embedded
      in host cell membranes and aids in the transportation of bacterial effectors. In
      addition, EspA is closely associated with initial bacterial adhesion and the
      formation of biofilms. EspA in its various forms elicits protective immune
      responses, although the epitope responsible has not to be identified. Here we
      report the presence of a linear, immunogenic, conserved and partially protective
      epitope E07 (100Lys-120Val) on EspA, which is recognized by the novel monoclonal
      antibody 1H10. This antibody blocks EHEC-induced actin polymerization and confers
      protection in mice. These findings provide a better understanding of EspA-induced
      immune responses and could lead to epitope-based vaccines and antibody-based
      therapies.

PMID- 21075693
TI  - Toe to hand transfer in children: ten year follow up of psychological aspects.
AB  - Our previous study found positive psychosocial effects from hand reconstruction
      in children, by microsurgical toe transfer. The aim of the current study was to
      determine whether these are enduring at ten years or more postoperatively. Twenty
      five patients with congenital (n=21) or post-traumatic (n=4) hand anomalies
      underwent transfer of either one or two toes. (Nineteen of the patients had taken
      part in the previous study while six had not.) All families had undergone
      preoperative counselling. Ten years or more after surgery, the patients and their
      parents underwent review to assess the long-term psychosocial outcome of the
      surgery. As in the previous study, a high level of satisfaction was reported, in
      terms of function, appearance, donor site, psychosocial well-being and the
      reactions of others. This was true regardless of the gender of the child. Patient
      and parent responses were more similar to each other than they had been in the
      earlier study. It was concluded that the positive effects of toe transfer surgery
      are enduring at long-term follow-up.

PMID- 21075692
TI  - Regional differences in neostigmine-induced contraction and relaxation of stomach
      from diabetic guinea pig.
AB  - Delayed gastric emptying and autonomic neuropathy have been documented in
      patients with diabetes mellitus. Some medications used to treat delayed gastric
      emptying enhance release of acetylcholine from autonomic neurons to strengthen
      gastric contractions. Autonomic coordination among gastric regions may be altered
      in diabetes resulting in poor outcomes in response to prokinetic drugs. Fundus,
      antrum, and pylorus from STZ or control guinea pigs were treated with neostigmine
      to mimic release of acetylcholine from autonomic neurons by prokinetic agents. In
      diabetic animals, neostigmine-induced contractions were weaker in fundus and
      pylorus but similar in antrum. The muscarinic receptor antagonist 4-DAMP or the
      nicotinic receptor antagonist hexamethonium reduced neostigmine-induced
      contractions. Activation of presynaptic muscarinic receptors on nitrergic neurons
      was impaired in fundus and antrum from diabetic animals. Nerve-stimulated
      contractions and relaxations, number of nNOS myenteric neurons, and tissue
      choline content were reduced in fundus from diabetic animals. Despite reduced
      number of myenteric neurons, tissue choline content was increased in antrum from
      diabetic animals. Since cholinergic motility of each gastric region was affected
      differently by diabetes, prokinetic drugs that nondiscriminately enhance
      acetylcholine release from autonomic neurons may not effectively normalize
      delayed gastric emptying in patients with diabetes and more selective medications
      may be warranted.

PMID- 21075694
TI  - [Diabetes and chronic kidney disease: lessons from renal epidemiology].
AB  - In industrialized countries, renal epidemiology is faced with the growing
      epidemic of diabetes as cause of renal involvement or as an associated condition.
      In France, recent studies estimate that 400,000+ diabetics have a glomerular
      filtration rate lower than 60 mL/min/1.73 m2, and that 7000+ are prevalent in
      dialysis. The vast majority has type 2 diabetes. In type 1 diabetes, renal
      prognosis improved over the last decade due to available aggressive glycemic
      control and treatment with renin-angiotensin system inhibitors. Diabetes has a
      negative impact on survival in end-stage renal disease, particularly for type 1
      diabetes patients and for women with diabetes. In type 2 diabetes, improvement in
      early access to renal transplant could lead to improvement in outcomes, whereas
      they are usually contra-indicated for transplant because rapid decline in
      cardiovascular status on dialysis. All these epidemiological data help us to
      implement preventing measures and further researches in order to improve diabetes
      patient prognosis.

PMID- 21075695
TI  - Improving women's knowledge of prostaglandin induction of labour through the use
      of information brochures: a quasi-experimental study.
AB  - RESEARCH QUESTION: To gain a better understanding of women's baseline level of
      knowledge of induction of labour (IOL) and determine whether giving written
      information at the time IOL is decided, results in significant differences in
      knowledge and understanding of the process. METHODS: Fifty pregnant women
      undergoing antenatal care at a small maternity hospital were recruited. A quasi
      experimental trial was conducted with non random selection of participants, 25
      selected to act as the control group and 25 selected as the intervention group.
      The study was conducted to determine women's knowledge of IOL both before (non
      intervention) and after (intervention) the introduction of a written information
      brochure. RESULTS: Statistically significant increases in knowledge were evident
      in the intervention group for knowledge about action (p=0.002) and timing of
      prostaglandins (p=0.03), the number of side effects known (p<0.0001) as well as
      time to birth (p=0.001) indicating an increased understanding of the process as a
      result of reading an information brochure. DISCUSSION: These results suggest that
      those in the non-intervention group lacked knowledge pertinent to IOL, even
      though they have consented to and actually arrived at the hospital prepared to
      undergo the IOL procedure. The most significant disparity noted between the
      intervention and non-intervention groups was women's knowledge of side effects of
      prostaglandin. Further to this, many women in the non-intervention group had
      unrealistic expectations of both the time for drug action and likely time from
      prostaglandin administration to birth. In contrast women in the intervention
      group knew about the common side effects of prostaglandin and possessed a more
      realistic understanding of the likely time to birth following this procedure.
      CONCLUSIONS: The results indicate that a specifically designed information
      brochure explaining the process of IOL in plain language has the effect of
      enhancing women's knowledge. This area of study warrants further investigation,
      especially research into the role of written information to improve women's
      understanding across other areas of maternity care education provision.

PMID- 21075696
TI  - The GHEP-EMPOP collaboration on mtDNA population data--A new resource for
      forensic casework.
AB  - Mitochondrial DNA (mtDNA) population data for forensic purposes are still scarce
      for some populations, which may limit the evaluation of forensic evidence
      especially when the rarity of a haplotype needs to be determined in a database
      search. In order to improve the collection of mtDNA lineages from the Iberian and
      South American subcontinents, we here report the results of a collaborative study
      involving nine laboratories from the Spanish and Portuguese Speaking Working
      Group of the International Society for Forensic Genetics (GHEP-ISFG) and EMPOP.
      The individual laboratories contributed population data that were generated
      throughout the past 10 years, but in the majority of cases have not been made
      available to the scientific community. A total of 1019 haplotypes from Iberia
      (Basque Country, 2 general Spanish populations, 2 North and 1 Central Portugal
      populations), and Latin America (3 populations from Sao Paulo) were collected,
      reviewed and harmonized according to defined EMPOP criteria. The majority of data
      ambiguities that were found during the reviewing process (41 in total) were
      transcription errors confirming that the documentation process is still the most
      error-prone stage in reporting mtDNA population data, especially when performed
      manually. This GHEP-EMPOP collaboration has significantly improved the quality of
      the individual mtDNA datasets and adds mtDNA population data as valuable resource
      to the EMPOP database (www.empop.org).

PMID- 21075697
TI  - Stem cell integrins: implications for ex-vivo culture and cellular therapies.
AB  - Use of stem cells, whether adult or embryonic for clinical applications to treat
      diseases such as Parkinson's, macular degeneration or Type I diabetes will
      require a homogenous population of mature, terminally differentiated cells. A
      current area of intense interest is the development of defined surfaces for stem
      cell derivation, maintenance, proliferation and subsequent differentiation, which
      are capable of replicating the complex cellular environment existing in vivo.
      During development many cellular cues result from integrin signalling induced by
      the local extracellular matrix. There are 24 known integrin heterodimers
      comprised of one of 18 alpha subunits and one of 8 beta subunits and these have a
      diverse range of functions mediating cell-cell adhesion, growth factor receptor
      responses and intracellular signalling cascades for cell migration,
      differentiation, survival and proliferation. We discuss here a brief summary of
      defined conditions for human embryonic stem cell culture together with a
      description of integrin function and signalling pathways. The importance of
      integrin expression during development is highlighted as critical for lineage
      specific cell function and how consideration of the integrin expression profile
      should be made while differentiating stem cells for use in therapy. In addition
      this review summarises the known integrin expression profiles for human embryonic
      stem cells and 3 common adult stem cell types: mesenchymal, haematopoietic and
      neural. We then outline some of the possible technologies available for
      investigating cell-extracellular matrix interactions and subsequent integrin
      mediated cell responses.

PMID- 21075698
TI  - Primary or recurring extra-abdominal desmoid fibromatosis: assessment of
      treatment by observation only.
AB  - INTRODUCTION: Extra-abdominal desmoid fibromatosis (EADF) is a benign tumoral
      condition, classically managed by more or less radical and sometimes mutilating
      excision. This treatment strategy is associated with a recurrence rate of nearly
      50% according to various reports. HYPOTHESIS: EADF may show spontaneous
      stabilization over time. METHODS: A retrospective series of 26 cases of EADF
      managed by simple observation was studied to assess spontaneous favorable
      evolution and identify possible factors impacting evolution. Eleven cases were of
      primary EADF with no treatment or surgery, and 15 of recurrence after surgery
      with no adjuvant treatment. MRI was the reference examination during follow-up.
      RESULTS: Twenty-four cases showed stabilization at a median 14 months; there were
      no cases of renewed evolution after stabilization. One primary tumor showed
      spontaneous regression, and one recurrence still showed evolution at end of
      follow-up (23 months). The sole factor impacting potential for evolution was
      prior surgery. No radiologic or pathologic criteria of evolution emerged from
      analysis. DISCUSSION: The present series, one of the largest dedicated to EADF
      managed by observation, confirmed recent literature findings: a conservative
      "wait-and-see" attitude is reasonable and should be considered when large-scale
      resection would entail significant functional or esthetic impairment. LEVEL OF
      EVIDENCE: Level IV, retrospective study.

PMID- 21075699
TI  - A continuous challenge from Gram-negative bacteria: more carbapenemases.

PMID- 21075700
TI  - Application of a molecular method for the classification of human enteroviruses
      and its correlation with clinical manifestations.
AB  - BACKGROUND/PURPOSE: A new molecular classification scheme has recently been
      adopted that groups all enteroviruses into four species, designated human
      enterovirus A (HEV-A) through D. In this study, we tried to demonstrate the
      correlation between this molecular classification scheme and clinical
      manifestations in patients. METHODS: We retrospectively reclassified the clinical
      isolates of enteroviruses from the preceding 4.5 years in our virology laboratory
      using reverse transcription-polymerase chain reaction, and reviewed the clinical
      manifestations of 138 pediatric patients. RESULTS: We reclassified 23 isolates of
      the five serotypes into the HEV-A group, 110 isolates of 16 sero-types into the
      HEV-B group, five isolates into the HEV-C group, and no isolate of the HEV-D
      group. HEV-A species caused significantly more hand-foot-and-mouth disease (p <
      0.001), herpangina (p = 0.029), and myoclonic jerks (p < 0.001) compared with HEV
      B species. However, HEV-B species caused significantly more pharyngitis (p =
      0.043), respiratory tract infections (p = 0.046), nausea and vomiting (p =
      0.007), and aseptic meningitis (p = 0.001). The only death in our report was
      caused by coxsackievirus A16, which belonged to the HEV-A group. CONCLUSION: The
      association between the molecular classification of enteroviruses and related
      disease patterns is an important finding. We suggest that this molecular
      classification could be applied in a clinical laboratory as an alternative method
      under certain circumstances, such as limited availability of antisera or
      questionable serotyping results, to identify the untypeable isolates.

PMID- 21075701
TI  - Hospitalized pediatric parainfluenza virus infections in a medical center.
AB  - BACKGROUND/PURPOSE: Parainfluenza viruses (PIVs) are common pathogens in
      respiratory tract infections. The aims of this study were to determine the
      clinical presentation of PIV infections in hospitalized children and to identify
      particular clinical indications that may effectively distinguish between
      different PIV serotypes. METHODS: A retrospective review of data from children
      hospitalized with PIV infections at the Mackay Memory Hospital in Taipei between
      January 2005 and December 2007 was undertaken. Symptoms, signs, laboratory
      findings and seasonal variations between different types of PIV (serotypes 1, 2
      and 3) were compared. RESULTS: A total of 206 patients [119 (57.8%) boys and 87
      (42.2%) girls] were enrolled in the study. Seventy-four (35.9%) patients were
      infected with PIV serotype 1, 25 (12.1%) with serotype 2 and 107 (51.9%) with
      serotype 3. The most common clinical presentations were fever (81.1%), cough
      (66.0%), rhinorrhea (44.2%) and hoarseness (22.3%); 4.9% of the infected children
      also had skin rashes. No significant differences were found in average white
      blood cell counts and C-reactive protein levels between the three serotypes. PIV
      serotype 1 infections were discernible throughout the year; serotype 2 tended to
      cluster in the late summer and autumn of 2005 and 2007; and serotype 3 was more
      common in the spring and early summer. CONCLUSION: The clinical presentation of
      PIV infection in hospitalized children ranges from upper respiratory tract
      infection to croup, bronchiolitis and viral bronchopneumonia, with the different
      types of PIV infections giving rise to similar symptoms. The seasonal
      distribution of the different serotypes is, nevertheless, quite distinct.

PMID- 21075702
TI  - Clinical presentations, laboratory results and outcomes of patients with
      Kikuchi's disease: emphasis on the association between recurrent Kikuchi's
      disease and autoimmune diseases.
AB  - BACKGROUND/PURPOSE: Kikuchi's disease (KD), also known as histiocytic necrotizing
      lymphadenitis, is a benign and self-limiting disease of unknown etiology that
      mainly affects young women. There is limited data on the long-term prognosis of
      patients with KD. METHODS: We describe the clinical manifestations and outcomes
      of 195 patients, diagnosed as having KD at National Taiwan University Hospital
      from March 1989 to September 2006. RESULTS: All together, 53.3% of our patients
      presented with tender lymphadenopathy, 37.9% with fever and 16.9% with headache.
      The most common laboratory findings were elevated erythrocyte sedimentation rate
      (78.9%), elevated serum lactate dehydrogenase (52.5%), elevated C-reactive
      protein (38.3%), monocytosis (26.9%), elevated serum alanine aminotransferase
      (23.3%) and leukopenia (18.9%). A total of 183 patients followed a benign course,
      with spontaneous resolution of fever and lymphadenopathy. However, 14 patients
      (14.6%) with follow-up of more than 6 months had clinical recurrence of KD;
      hence, long-term follow-up is suggested. Five of these patients developed an
      autoimmune disease, namely, systemic lupus erythematosus (n = 2), Graves' disease
      (n = 2), or mixed connective tissue disease (n = 1). One patient with recurrent
      KD died of intracranial hemorrhage due to thrombocytopenia. CONCLUSION: The
      prognosis for KD patients is generally optimistic; however, a concurrent
      autoimmune disease or the risk of developing an autoimmune disease requires
      careful monitoring.

PMID- 21075703
TI  - Performance of the BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA)
      PCR assay for detecting MRSA nasal colonization in Taiwanese adults.
AB  - BACKGROUND/PURPOSE: A rapid diagnostic method for methicillin-resistant
      Staphylococcus aureus (MRSA) has been implemented for surveillance of the at-risk
      population, but its performance in those without traditional risk factors is not
      clear. The objective of this study was to evaluate MRSA colonization status by
      comparing the performance of the BD GeneOhm MRSA polymerase chain reaction (PCR)
      assay with that of conventional culture during a 3-month active surveillance of
      Taiwanese adults in the community. METHODS: From 1 October 2007 to 28 December
      2007, adults (>= 18 years old) attending a mandatory health examination arranged
      by their employers as a part of the workplace health promotion program at three
      medical centers in northern Taiwan were enrolled in the study. No healthcare
      workers were included. A total of 498 paired nasal swabs were prospectively
      obtained and used for both the BD GeneOhm MRSA PCR assay and conventional
      culture. RESULTS: Of the 498 paired nasal swabs, 14 (2.8%) were positive for MRSA
      by conventional culture and 34 (6.8%) were positive by the BD GeneOhm MRSA PCR
      assay (p < 0.005). Thirteen specimens were both culture- and PCR-positive, and
      463 samples were both culture- and PCR-negative. There were two discordant
      results: 21 specimens were culture-negative/PCR-positive, and one was culture
      positive/PCR-negative. The simple kappa coefficient for measuring the agreement
      between conventional culture and the MRSA PCR assay was 0.52. CONCLUSION: This
      study demonstrates the feasibility of using both the MRSA PCR assay and
      conventional culture as surveillance tools. Also, the MRSA-positive rate detected
      by MRSA PCR assay was significantly higher than that of conventional culture.

PMID- 21075704
TI  - Outcome and risk factors associated with surgical site infections after cardiac
      surgery in a Taiwan medical center.
AB  - BACKGROUND/PURPOSE: Surgical site infection (SSI) after cardiac surgery leads to
      morbidity and mortality. Identifying SSI risk factors, which vary between
      populations, is important in preventing infection. METHODS: A retrospective chart
      review of adult cases receiving cardiac surgery in a Taiwan medical center in
      2004 and 2005. RESULTS: Of the 260 cases included in the study, 169 (65.0%)
      received a coronary artery bypass graft, 65 (25.0%) cardiac valvular surgery and
      26 (10.0%) aortic or septal defect operations. The SSI rate was 13.5%. Univariate
      analysis showed that chronic obstructive pulmonary disease (COPD) (p = 0.008),
      congestive heart failure New York Heart Association class IV (p = 0.048), longer
      preoperative hospital stay, preoperative nosocomial infection, higher volume of
      blood loss and larger packed red blood cell transfusions during the operation
      were significantly related to SSI. Logistic regression analysis further
      identified COPD, pre-operative nosocomial infection and emergency surgery as
      being independently associated with SSI (odds ratios of 4.96, 5.88 and 9.77,
      respectively). Obesity and diabetes mellitus were not associated with SSI.
      CONCLUSION: COPD is an independent underlying illness associated with SSI after
      cardiac surgery. Minimizing preoperative hospitalization and nosocomial
      infection, and awareness of cases presenting with relevant risk factors, are
      useful in reducing SSI.

PMID- 21075705
TI  - Does radiographic evidence of prior pulmonary tubercular infection influence the
      choice of empiric antibiotics for community-acquired pneumonia in a tuberculosis
      endemic area?
AB  - BACKGROUND/PURPOSE: Recent medical literature suggests that use of
      fluoroquinolones (FQs) might be associated with the delayed diagnosis of
      pulmonary tuberculosis (TB). The purpose of this study was to assess the impact
      of radiographic evidence of prior pulmonary TB infection on empiric antibiotic
      choice in cases of community-acquired pneumonia (CAP), as well as the effect of
      antibiotic regimens on clinical outcome. METHODS: A total of 280 patients with
      CAP between 1 May and 31 December 2007 were included in the study and their
      medical records were retrospectively reviewed. Patients were divided into two
      groups: those receiving FQs (FQ group) or those receiving beta-lactam-based
      regimens (beta-lactam group). Their demographic data, underlying diseases,
      clinical features, diseases severity and outcomes were compared. RESULTS:
      Radiographic evidence of a previous pulmonary TB infection (odds ratio = 3.507,
      95% confidence interval = 1.422-8.645; p = 0.006) was an independent factor
      associated with beta-lactam-based regimens. Patients with a modified pneumonia
      severity index (mPSI) category V were more likely to receive FQ therapy (odds
      ratio = 2.53, 95% confidence interval = 1.140-5.615; p = 0.022). Of the patients
      with mPSI category V, the 14-day mortality rate of those in the beta-lactam group
      was significantly lower than that of those in the FQ group (0%vs. 23%,
      respectively; p = 0.044). CONCLUSION: Radiographic evidence of a previous
      pulmonary TB infection and a lower mPSI score increases the probability of the
      selection of a beta-lactam-based regimen for the treatment of CAP.

PMID- 21075706
TI  - Abdominal tuberculosis in adult: 10-year experience in a teaching hospital in
      central Taiwan.
AB  - BACKGROUND/PURPOSE: Tuberculosis (TB) is an important communicable disease
      worldwide. The clinical presentation of abdominal TB often mimics various
      gastrointestinal disorders and may delay accurate diagnosis. In this study, we
      conducted a 10-year retrospective study to investigate the clinical
      manifestations, treatment responses and outcomes of abdominal TB. METHODS: This
      retrospective study recruited patients presenting between January 1998 and
      December 2007; all patients >= 18 years of age with a diagnosis of abdominal TB
      were enrolled. Patient charts were thoroughly reviewed and clinical specimens
      were processed in the laboratory using the BBL MycoPrep System and BACTEC MGIT
      960 Mycobacterial Detection System. Mycobacterium tuberculosis complex was
      confirmed by acid fast stain and the BD ProbeTec ET System. RESULTS: During the
      study period, 34 patients were diagnosed with abdominal TB. The mean age was
      55+18 years. Fourteen patients (41%) had no risk factors; however, 20 patients
      (59%) had at least one risk factor. Abdominal pain (94.1%), abdominal fullness
      (91.2%), anorexia (88.2%) and ascites (76.5%) were the most common presenting
      symptoms. The peritoneum (88%) was the most commonly involved site. Patients with
      risk factors such as liver cirrhosis, end-stage renal disease and diabetes
      mellitus had a higher positive rate of acid-fast stain and mycobacterial culture
      from abdominal specimens (p = 0.02 and 0.05, respectively). The crude mortality
      rate was 9% and the attributed mortality rate was 3%. CONCLUSION: In an endemic
      area like Taiwan, regardless of whether a patient has risk factors for TB,
      abdominal TB should be seriously considered as a differential diagnosis when a
      patient presents with gastrointestinal symptoms and unexplained ascites.

PMID- 21075707
TI  - Clinical outcome of Mycobacterium abscessus infection and antimicrobial
      susceptibility testing.
AB  - BACKGROUND/PURPOSE: Mycobacterium abscessus is the most resistant and rapidly
      growing mycobacterium and causes a wide range of clinical infectious diseases.
      The relationship between antimicrobial susceptibility and clinical outcome needs
      to be further evaluated. METHODS: Forty M. abscessus isolates were obtained from
      clinical specimens of 40 patients at the Taichung Veterans General Hospital from
      January 2006 to December 2008. Antimicrobial susceptibility testing was performed
      using the broth microdilution method according to the recommendations of the
      National Committee for Clinical Laboratory Standards. The clinical manifestations
      and outcomes were reviewed from medical records. RESULTS: Twenty-two patients
      were diagnosed with M. abscessus infection. Cough (86.3%), hemoptysis (31.8%) and
      fever (18.1%) were the most common symptoms. The radiographic findings included
      reticulonodular opacities (50.0%), consolidation (31.8%) and cavitary lesions
      (18.1%). The 40 isolates were susceptible to amikacin (95.0%), cefoxitin (32.5%),
      ciprofloxacin (10.0%), clarithromycin (92.5%), doxycycline (7.5%), imipenem
      (12.5%), moxifloxacin (22.5%), sulfamethoxazole (7.5%) and tigecycline (100%).
      The rate of treatment failure was 27.3% at the end of the 12(th) month after the
      start of treatment, although these patients were treated with a combination of
      clarithromycin and other antimicrobial agents. CONCLUSION: M. abscessus is
      naturally susceptible to clarithromycin and amikacin, variably susceptible to
      cefoxitin and imipenem, and resistant to most other antimicrobial drugs.
      Combination therapy with clarithromycin, amikacin and other active antimicrobial
      agents may lead to clinical improvement; however, the rate of treatment failure
      is still high.

PMID- 21075708
TI  - Long-term characteristics of healthcare-associated infections in a neonatal
      intensive care unit.
AB  - BACKGROUND/PURPOSE: Healthcare-associated infections in neonatal intensive care
      units (NICUs) are associated with a significant risk of morbidity and mortality.
      Knowledge regarding pathogens, primary sources of infection and antibiotic
      resistance in the NICU is essential for developing management strategies. This
      study aimed to analyze the long-term characteristics of healthcare-associated
      infections in a tertiary referral center in southern Taiwan. METHODS: Infants <
      30 days old, with positive blood, cerebrospinal fluid, urine or tissue fluid
      cultures during hospitalization in the NICU of National Cheng Kung University
      Hospital from July 1989 to June 2008 were included in the study. RESULTS: In
      total, 1,417 organisms and episodes were identified during the study period. Gram
      positive organisms, Gram-negative organisms and fungi constituted 923 (65.1%),
      358 (25.3%) and 136 (9.6%) of the pathogens, respectively. Of the Gram-positive
      organisms, coagulase-negative staphylococci (51.5%), Staphylococcus aureus
      (34.8%) and Enterococcus spp. (6.1%) were the major pathogens; and 27% of
      Staphylococcus aureus isolates were oxacillin-resistant. For the Gram-negative
      organisms, Klebsiella pneumoniae (22%), Pseudomonas aeruginosa (21.8%),
      Escherichia coli (16.7%) and Enterobacter cloacae (16.7%) were dominant. Also,
      Candida albicans accounted for 50% of fungal infections. The most common source
      of infection was bloodstream infection (59.0%), and 5.6% of these were catheter
      related. Skin and soft tissue infections were also frequent (26.3%). CONCLUSION:
      Bloodstream and skin/soft tissue infections caused by commensal species play an
      important role in healthcare-associated infections in the NICU. New measures
      should be developed in response to the changing patterns in the NICU.

PMID- 21075709
TI  - Changing epidemiology of nosocomial bloodstream infections in 11 teaching
      hospitals in Taiwan between 1993 and 2006.
AB  - BACKGROUND/PURPOSE: Healthcare-associated infections, formerly known as
      nosocomial infections, are one of the most important issues in current practice.
      Understanding trends in overall infection rates, as well as their incidence and
      proportion among different causative organisms, can help us to better define our
      infection control methods and therapy goals. To understand the changing
      epidemiology of nosocomial bloodstream infections (BSI) in Taiwan, we
      retrospectively collected nosocomial infection data from 11 hospitals and
      examined the trends and changing patterns of nosocomial BSI. METHODS: Eleven
      major teaching hospitals in Taiwan were invited to participate in the study. The
      overall density of nosocomial infections and major BSI-causing organisms,
      including Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii,
      and Candida species, were collected. The distribution of the different Candida
      species was also recorded. Background parameters from the 11 hospitals, including
      the size of the hospital, hospital capacity, the number of blood stream infection
      events, and average length of stay, were also recorded. RESULTS: The incidence of
      nosocomial BSI ranged 0.23-2.56 per 1,000 patient-days, which accounted for 8-43%
      of all nosocomial infections. The most common causative organism of nosocomial
      bacteremia was S. aureus, ranging 0.88-0.01 per 1,000 patient-days. Overall, the
      incidence of S. aureus bacteremia has decreased over the last 13 years, but this
      difference was not statistically significant (p = 0.053). The rate of Candida
      fungemia (p < 0.01) and A. baumannii (p = 0.03) bacteremia increased
      significantly. C. albicans accounted for most cases of nosocomial fungemia,
      ranging from 40% to 80%, followed by Candida tropicalis, Candida parapsilosis and
      Candida glabrata. However, the incidence varied significantly from hospital to
      hospital, and the highest incidence was observed in a cancer center. CONCLUSION:
      The overall incidence rate of S. aureus bacteremia in the 11 major hospitals
      studied had decreased over the last decade, though the difference was not
      statistically significant. However, the rate of Candida fungemia and A. baumannii
      bacteremia had increased significantly.

PMID- 21075710
TI  - Infectious endocarditis in pediatric patients: analysis of 19 cases presenting at
      a medical center.
AB  - BACKGROUND/PURPOSE: Infectious endocarditis (IE) is a rare, but potentially fatal
      disease in pediatric patients. In this study, we reviewed the symptoms and signs,
      etiology, laboratory findings and outcomes of IE patients over the past 10 years.
      METHODS: Patients (< 18 years old) with definite IE according to the modified
      Duke criteria, or patients with positive pathological findings, between September
      1998 and September 2008 were included in the study. The etiology, symptoms and
      signs, laboratory findings and outcomes were collected via chart review. RESULTS:
      Nineteen cases (13 boys and 6 girls) ranging in age from 2.5 months to 18 years
      (mean = 7.98 years; median = 5 years) were included. Nine out of 17 cases (52.9%)
      had microscopic hematuria and two out of three (66.7%) cases showed elevated
      rheumatoid factor levels. Seventeen (89.5%) had fever and seven (36.8%) had major
      vessel embolic events. Blood cultures yielded Staphylococcus aureus in seven
      cases, and viridans Streptococci in two cases. The other three cases had
      Pneumococcus, Pseudomonas aeruginosa and Candida albicans. Two patients died and
      one was discharged in a critical condition. Two of the seven (28.6%) patients
      with a positive blood culture for S. aureus died, three (42.9%) had an embolic
      event and one (14.3%) had central nervous system complications (intracranial
      hemorrhage). The initial C-reactive protein levels in the blood culture-positive
      group were significantly higher than those in the blood culture-negative group (p
      = 0.035). CONCLUSION: S. aureus is one of the most common etiologies in IE
      patients, while viridans Streptococcus accounts for fewer cases than suggested by
      previous studies. IE caused by S. aureus seems to carry a higher risk of
      mortality, and embolic events are associated with increased mortality.

PMID- 21075711
TI  - Gemella haemolysans bacteraemia in a patient with solitary liver abscess.
AB  - We present a case of a 42-year-old man with a solitary liver abscess and Gemella
      haemolysans bacteraemia. No other focus of infection was identified. The patient
      did not have any predisposing factors. He was treated with antibiotics for 6
      weeks and the abscess was drained. He made a complete recovery.

PMID- 21075712
TI  - Management of patients with huge pelvic actinomycosis complicated with
      hydronephrosis: a case report.
AB  - Actinomycosis is an uncommon, chronic, granulomatous disease caused by several
      species of the genus Actinomyces, a Gram-positive, filamentous bacterium that
      normally colonizes mucosal areas. Actinomycosis can be mistaken for malignant
      tumors, and in most cases the diagnosis is delayed or missed entirely until
      surgery. Actinomycosis in the abdomen or pelvis mostly results from prolonged use
      of an intrauterine device. We report the case of a 40-year-old female who
      presented with decreased urine production, poor appetite, marked loss of body
      weight and intermittent lower abdominal pain for 3 months. Abdominal computed
      tomography indicated a large infiltrative pelvic mass that was complicated by
      bilateral hydronephrosis, bladder compression and small bowel adhesions. Despite
      the elevated levels of cancer antigen 125, we suspected pelvic actinomycosis
      because of a 15-year history of an intrauterine device. The diagnosis was
      confirmed by histopathological examination of soft tissue obtained from a
      laparotomy biopsy. We successfully treated the patient with prolonged antibiotics
      instead of surgical eradication. Abdominal computed tomography obtained 1 year
      later showed almost complete resolution of the pelvic inflammatory mass.

PMID- 21075713
TI  - Effect of plant oils on Candida albicans.
AB  - BACKGROUND/PURPOSE: Candida species, notably Candida albicans, is the major
      fungal pathogen in humans. It is a dimorphic fungus capable of causing
      superficial mucosal infections, as well as systemic infections, in
      immunocompromised individuals. The factors responsible for its pathogenesis are
      still not fully understood and increasing resistance to commonly used antifungal
      agents necessitates the search for new formulations. METHODS: The inhibitory
      effect of 30 different plant oils on Candida albicans isolated from clinical
      samples was evaluated. The antifungal agent fluconazole was used as a positive
      control. Plant oils were tested at concentrations from 0.03% to 3% (v/v) to
      determine the minimum inhibitory concentration and minimum fungicidal
      concentration (MFC) using agar dilution and macro broth dilution assays. RESULTS:
      Of the 30 plant oils tested, 18 were found to be effective and 12 were
      ineffective. Based on their MFCs, effective oils were placed into three
      categories: most effective, moderately effective and least effective. Eucalyptus
      and peppermint oils were most effective, with MFC values of 0.12% and 0.15%
      (v/v), respectively. CONCLUSION: The significant antifungal activity of these
      oils suggests that they could serve as a source of compounds with therapeutic
      potential against Candida-related infections.

PMID- 21075714
TI  - Consensus statement on the adherence to Clinical and Laboratory Standards
      Institute (CLSI) Antimicrobial Susceptibility Testing Guidelines (CLSI-2010 and
      CLSI-2010-update) for Enterobacteriaceae in clinical microbiology laboratories in
      Taiwan.

PMID- 21075715
TI  - Detection of clinical depression in adolescents' speech during family
      interactions.
AB  - The properties of acoustic speech have previously been investigated as possible
      cues for depression in adults. However, these studies were restricted to small
      populations of patients and the speech recordings were made during patients'
      clinical interviews or fixed-text reading sessions. Symptoms of depression often
      first appear during adolescence at a time when the voice is changing, in both
      males and females, suggesting that specific studies of these phenomena in
      adolescent populations are warranted. This study investigated acoustic correlates
      of depression in a large sample of 139 adolescents (68 clinically depressed and
      71 controls). Speech recordings were made during naturalistic interactions
      between adolescents and their parents. Prosodic, cepstral, spectral, and glottal
      features, as well as features derived from the Teager energy operator (TEO), were
      tested within a binary classification framework. Strong gender differences in
      classification accuracy were observed. The TEO-based features clearly
      outperformed all other features and feature combinations, providing
      classification accuracy ranging between 81%-87% for males and 72%-79% for
      females. Close, but slightly less accurate, results were obtained by combining
      glottal features with prosodic and spectral features (67%-69% for males and 70%
      75% for females). These findings indicate the importance of nonlinear mechanisms
      associated with the glottal flow formation as cues for clinical depression.

PMID- 21075716
TI  - Towards brain first-aid: a diagnostic device for conscious awareness.
AB  - When the brain is damaged, evaluating an individual's level of awareness can be a
      major diagnostic challenge (Is he or she in there?). Existing tests typically
      rely on behavioral indicators, which are incorrect in as many as one out of every
      two cases. The current paper presents a diagnostic device that addresses this
      problem. The technology circumvents behavioral limitations through noninvasive
      brain wave measurements (electroencephalography, or EEG). Unlike traditional EEG,
      the device is designed for point-of-care use by incorporating a portable, user
      friendly, and stable design. It uses a novel software algorithm that automates
      subject stimulation, data acquisition/analysis, and the reporting of results. The
      test provides indicators for five identifiable levels of neural processing:
      sensation, perception, attention, memory, and language. The results are provided
      as rapidly obtained diagnostic, reliability, validity, and prognostic scores. The
      device can be applied to a wide variety of patients across a host of different
      environments. The technology is designed to be wireless-enabled for remote
      monitoring and assessment capabilities. In essence, the device is developed to
      scan for conscious awareness in order to optimize subsequent patient care.

PMID- 21075717
TI  - Real-time regularized ultrasound elastography.
AB  - This paper introduces two real-time elastography techniques based on analytic
      minimization (AM) of regularized cost functions. The first method (1D AM)
      produces axial strain and integer lateral displacement, while the second method
      (2D AM) produces both axial and lateral strains. The cost functions incorporate
      similarity of radio-frequency (RF) data intensity and displacement continuity,
      making both AM methods robust to small decorrelations present throughout the
      image. We also exploit techniques from robust statistics to make the methods
      resistant to large local decorrelations. We further introduce Kalman filtering
      for calculating the strain field from the displacement field given by the AM
      methods. Simulation and phantom experiments show that both methods generate
      strain images with high SNR, CNR and resolution. Both methods work for strains as
      high as 10% and run in real-time. We also present in vivo patient trials of
      ablation monitoring. An implementation of the 2D AM method as well as phantom and
      clinical RF-data can be downloaded.

PMID- 21075718
TI  - General approach to first-order error prediction in rigid point registration.
AB  - A general approach to the first-order analysis of error in rigid point
      registration is presented that accommodates fiducial localization error (FLE)
      that may be inhomogeneous (varying from point to point) and anisotropic (varying
      with direction) and also accommodates arbitrary weighting that may also be
      inhomogeneous and anisotropic. Covariances are derived for target registration
      error (TRE) and for weighted fiducial registration error (FRE) in terms of
      covariances of FLE, culminating in a simple implementation that encompasses all
      combinations of weightings and anisotropy. Furthermore, it is shown that for
      ideal weighting, in which the weighting matrix for each fiducial equals the
      inverse of the square root of the cross covariance of its two-space FLE,
      fluctuations of FRE and TRE are mutually independent. These results are validated
      by comparison with previously published expressions and by simulation.
      Furthermore, simulations for randomly generated fiducial positions and FLEs are
      presented that show that correlation is negligible (correlation coefficient <
      0.1) in the exact case for both ideal and uniform weighting (i.e., no weighting),
      the latter of which is employed in commercial surgical guidance systems. From
      these results we conclude that for these weighting schemes, while valid
      expressions exist relating the covariance of FRE to the covariance of TRE, there
      are no measures of the goodness of fit of the fiducials for a given registration
      that give to first order any information about the fluctuation of TRE from its
      expected value and none that give useful information in the exact case.
      Therefore, as estimators of registration accuracy, such measures should be
      approached with extreme caution both by the purveyors of guidance systems and by
      the practitioners who use them.

PMID- 21075720
TI  - Linear discriminant analysis for signatures.
AB  - We propose signature linear discriminant analysis (signature-LDA) as an extension
      of LDA that can be applied to signatures, which are known to be more informative
      representations of local image features than vector representations, such as
      visual word histograms. Based on earth mover's distances between signatures,
      signature-LDA does not require vectorization of local image features in contrast
      to LDA, which is one of the main limitations of classical LDA. Therefore,
      signature-LDA minimizes the loss of intrinsic information of local image features
      while selecting more discriminating features using label information. Empirical
      evidence on texture databases shows that signature-LDA improves upon state-of-the
      art approaches for texture image classification and outperforms other feature
      selection methods for local image features.

PMID- 21075719
TI  - Shear wave velocity imaging using transient electrode perturbation: phantom and
      ex vivo validation.
AB  - This paper presents a new shear wave velocity imaging technique to monitor radio
      frequency and microwave ablation procedures, coined electrode vibration
      elastography. A piezoelectric actuator attached to an ablation needle is
      transiently vibrated to generate shear waves that are tracked at high frame
      rates. The time-to-peak algorithm is used to reconstruct the shear wave velocity
      and thereby the shear modulus variations. The feasibility of electrode vibration
      elastography is demonstrated using finite element models and ultrasound
      simulations, tissue-mimicking phantoms simulating fully (phantom 1) and partially
      ablated (phantom 2) regions, and an ex vivo bovine liver ablation experiment. In
      phantom experiments, good boundary delineation was observed. Shear wave velocity
      estimates were within 7% of mechanical measurements in phantom 1 and within 17%
      in phantom 2. Good boundary delineation was also demonstrated in the ex vivo
      experiment. The shear wave velocity estimates inside the ablated region were
      higher than mechanical testing estimates, but estimates in the untreated tissue
      were within 20% of mechanical measurements. A comparison of electrode vibration
      elastography and electrode displacement elastography showed the complementary
      information that they can provide. Electrode vibration elastography shows promise
      as an imaging modality that provides ablation boundary delineation and
      quantitative information during ablation procedures.

PMID- 21075721
TI  - Minimum complexity echo state network.
AB  - Reservoir computing (RC) refers to a new class of state-space models with a fixed
      state transition structure (the reservoir) and an adaptable readout form the
      state space. The reservoir is supposed to be sufficiently complex so as to
      capture a large number of features of the input stream that can be exploited by
      the reservoir-to-output readout mapping. The field of RC has been growing rapidly
      with many successful applications. However, RC has been criticized for not being
      principled enough. Reservoir construction is largely driven by a series of
      randomized model-building stages, with both researchers and practitioners having
      to rely on a series of trials and errors. To initialize a systematic study of the
      field, we concentrate on one of the most popular classes of RC methods, namely
      echo state network, and ask: What is the minimal complexity of reservoir
      construction for obtaining competitive models and what is the memory capacity
      (MC) of such simplified reservoirs? On a number of widely used time series
      benchmarks of different origin and characteristics, as well as by conducting a
      theoretical analysis we show that a simple deterministically constructed cycle
      reservoir is comparable to the standard echo state network methodology. The
      (short-term) MC of linear cyclic reservoirs can be made arbitrarily close to the
      proved optimal value.

PMID- 21075722
TI  - ELITE: ensemble of optimal input-pruned neural networks using TRUST-TECH.
AB  - The ensemble of optimal input-pruned neural networks using TRUST-TECH (ELITE)
      method for constructing high-quality ensemble through an optimal linear
      combination of accurate and diverse neural networks is developed. The
      optimization problems in the proposed methodology are solved by a global
      optimization a global optimization method called TRansformation Under Stability
      reTraining Equilibrium Characterization (TRUST-TECH), whose main features include
      its capability in identifying multiple local optimal solutions in a
      deterministic, systematic, and tier-by-tier manner. ELITE creates a diverse
      population via a feature selection procedure of different local optimal neural
      networks obtained using tier-1 TRUST-TECH search. In addition, the capability of
      each input-pruned network is fully exploited through a TRUST-TECH-based optimal
      training. Finally, finding the optimal linear combination weights for an ensemble
      is modeled as a nonlinear programming problem and solved using TRUST-TECH and the
      interior point method, where the issue of non-convexity can be effectively
      handled. Extensive numerical experiments have been carried out for pattern
      classification on the synthetic and benchmark datasets. Numerical results show
      that ELITE consistently outperforms existing methods on the benchmark datasets.
      The results show that ELITE can be very promising for constructing high-quality
      neural network ensembles.

PMID- 21075723
TI  - Learning pattern recognition through quasi-synchronization of phase oscillators.
AB  - The idea that synchronized oscillations are important in cognitive tasks is
      receiving significant attention. In this view, single neurons are no longer
      elementary computational units. Rather, coherent oscillating groups of neurons
      are seen as nodes of networks performing cognitive tasks. From this assumption,
      we develop a model of stimulus-pattern learning and recognition. The three most
      salient features of our model are: 1) a new definition of synchronization; 2)
      demonstrated robustness in the presence of noise; and 3) pattern learning.

PMID- 21075724
TI  - An augmented echo state network for nonlinear adaptive filtering of complex
      noncircular signals.
AB  - A novel complex echo state network (ESN), utilizing full second-order statistical
      information in the complex domain, is introduced. This is achieved through the
      use of the so-called augmented complex statistics, thus making complex ESNs
      suitable for processing the generality of complex-valued signals, both second
      order circular (proper) and noncircular (improper). Next, in order to deal with
      nonstationary processes with large nonlinear dynamics, a nonlinear readout layer
      is introduced and is further equipped with an adaptive amplitude of the
      nonlinearity. This combination of augmented complex statistics and enhanced
      adaptivity within ESNs also facilitates the processing of bivariate signals with
      strong component correlations. Simulations in the prediction setting on both
      circular and noncircular synthetic benchmark processes and real-world noncircular
      and nonstationary wind signals support the analysis.

PMID- 21075725
TI  - 24-GOPS 4.5- mm2 digital cellular neural network for rapid visual attention in an
      object-recognition SoC.
AB  - This paper presents the Visual Attention Engine (VAE), which is a digital
      cellular neural network (CNN) that executes the VA algorithm to speed up object
      recognition. The proposed time-multiplexed processing element (TMPE) CNN topology
      achieves high performance and small area by integrating 4800 (80 * 60) cells and
      120 PEs. Pipelined operation of the PEs and single-cycle global shift capability
      of the cells result in a high PE utilization ratio of 93%. The cells are
      implemented by 6T static random access memory-based register files and dynamic
      shift registers to enable a small area of 4.5 mm(2). The bus connections between
      PEs and cells are optimized to minimize power consumption. The VAE is integrated
      within an object-recognition system-on-chip (SoC) fabricated in the 0.13- MUm
      complementary metal-oxide-semiconductor process. It achieves 24 GOPS peak
      performance and 22 GOPS sustained performance at 200 MHz enabling one CNN
      iteration on an 80 * 60 pixel image to be completed in just 4.3 MUs. With VA
      enabled using the VAE, the workload of the object-recognition SoC is
      significantly reduced, resulting in 83% higher frame rate while consuming 45%
      less energy per frame without degradation of recognition accuracy.

PMID- 21075726
TI  - Mixing linear SVMs for nonlinear classification.
AB  - In this paper, we address the problem of combining linear support vector machines
      (SVMs) for classification of large-scale nonlinear datasets. The motivation is to
      exploit both the efficiency of linear SVMs (LSVMs) in learning and prediction and
      the power of nonlinear SVMs in classification. To this end, we develop a LSVM
      mixture model that exploits a divide-and-conquer strategy by partitioning the
      feature space into subregions of linearly separable datapoints and learning a
      LSVM for each of these regions. We do this implicitly by deriving a generative
      model over the joint data and label distributions. Consequently, we can impose
      priors on the mixing coefficients and do implicit model selection in a top-down
      manner during the parameter estimation process. This guarantees the sparsity of
      the learned model. Experimental results show that the proposed method can achieve
      the efficiency of LSVMs in the prediction phase while still providing a
      classification performance comparable to nonlinear SVMs.

PMID- 21075727
TI  - CA-tree: a hierarchical structure for efficient and scalable coassociation-based
      cluster ensembles.
AB  - Cluster ensembles have attracted a lot of research interests in recent years, and
      their applications continue to expand. Among the various algorithms for cluster
      ensembles, those based on coassociation matrices are probably the ones studied
      and used the most because coassociation matrices are easy to understand and
      implement. However, the main limitation of coassociation matrices as the data
      structure for combining multiple clusterings is the complexity that is at least
      quadratic to the number of patterns N. In this paper, we propose CA-tree, which
      is a dendogram-like hierarchical data structure, to facilitate efficient and
      scalable cluster ensembles for coassociation-matrix-based algorithms. All the
      properties of the CA-tree are derived from base cluster labels and do not require
      the access to the original data features. We then apply a threshold to the CA
      tree to obtain a set of nodes, which are then used in place of the original
      patterns for ensemble-clustering algorithms. The experiments demonstrate that the
      complexity for coassociation-based cluster ensembles can be reduced to close to
      linear to N with minimal loss on clustering accuracy.

PMID- 21075728
TI  - Using the Dempster-Shafer theory of evidence with a revised lattice structure for
      activity recognition.
AB  - This paper explores a sensor fusion method applied within smart homes used for
      the purposes of monitoring human activities in addition to managing uncertainty
      in sensor-based readings. A three-layer lattice structure has been proposed,
      which can be used to combine the mass functions derived from sensors along with
      sensor context. The proposed model can be used to infer activities. Following
      evaluation of the proposed methodology it has been demonstrated that the Dempster
      Shafer theory of evidence can incorporate the uncertainty derived from the sensor
      errors and the sensor context and subsequently infer the activity using the
      proposed lattice structure. The results from this study show that this method can
      detect a toileting activity within a smart home environment with an accuracy of
      88.2%.

PMID- 21075729
TI  - An ontology-based system for context-aware and configurable services to support
      home-based continuous care.
AB  - Continuous care models for chronic diseases pose several technology-oriented
      challenges for home-based care, where assistance services rely on a close
      collaboration among different stakeholders, such as health operators, patient
      relatives, and social community members. This paper describes an ontology-based
      context model and a related context management system providing a configurable
      and extensible service-oriented framework to ease the development of applications
      for monitoring and handling patient chronic conditions. The system has been
      developed in a prototypal version, and integrated with a service platform for
      supporting operators of home-based care networks in cooperating and sharing
      patient-related information and coordinating mutual interventions for handling
      critical and alarm situations. Finally, we discuss experimentation results and
      possible further research directions.

PMID- 21075730
TI  - Noise-assisted data processing with empirical mode decomposition in biomedical
      signals.
AB  - In this paper, a methodology is described in order to investigate the performance
      of empirical mode decomposition (EMD) in biomedical signals, and especially in
      the case of electrocardiogram (ECG). Synthetic ECG signals corrupted with white
      Gaussian noise are employed and time series of various lengths are processed with
      EMD in order to extract the intrinsic mode functions (IMFs). A statistical
      significance test is implemented for the identification of IMFs with high-level
      noise components and their exclusion from denoising procedures. Simulation
      campaign results reveal that a decrease of processing time is accomplished with
      the introduction of preprocessing stage, prior to the application of EMD in
      biomedical time series. Furthermore, the variation in the number of IMFs
      according to the type of the preprocessing stage is studied as a function of SNR
      and time-series length. The application of the methodology in MIT-BIH ECG records
      is also presented in order to verify the findings in real ECG signals.

PMID- 21075731
TI  - Discrimination power of short-term heart rate variability measures for CHF
      assessment.
AB  - In this study, we investigated the discrimination power of short-term heart rate
      variability (HRV) for discriminating normal subjects versus chronic heart failure
      (CHF) patients. We analyzed 1914.40 h of ECG of 83 patients of which 54 are
      normal and 29 are suffering from CHF with New York Heart Association (NYHA)
      classification I, II, and III, extracted by public databases. Following
      guidelines, we performed time and frequency analysis in order to measure HRV
      features. To assess the discrimination power of HRV features, we designed a
      classifier based on the classification and regression tree (CART) method, which
      is a nonparametric statistical technique, strongly effective on nonnormal medical
      data mining. The best subset of features for subject classification includes
      square root of the mean of the sum of the squares of differences between adjacent
      NN intervals (RMSSD), total power, high-frequencies power, and the ratio between
      low- and high-frequencies power (LF/HF). The classifier we developed achieved
      sensitivity and specificity values of 79.3 % and 100 %, respectively. Moreover,
      we demonstrated that it is possible to achieve sensitivity and specificity of
      89.7 % and 100 %, respectively, by introducing two nonstandard features DeltaAVNN
      and DeltaLF/HF, which account, respectively, for variation over the 24 h of the
      average of consecutive normal intervals (AVNN) and LF/HF. Our results are
      comparable with other similar studies, but the method we used is particularly
      valuable because it allows a fully human-understandable description of
      classification procedures, in terms of intelligible "if ... then ..." rules.

PMID- 21075732
TI  - Noninvasive biological sensor system for detection of drunk driving.
AB  - Systems capable of monitoring the biological condition of a driver and issuing
      warnings during instances of drowsiness have recently been studied. Moreover,
      many researchers have reported that biological signals, such as brain waves,
      pulsation waves, and heart rate, are different between people who have and have
      not consumed alcohol. Currently, we are developing a noninvasive system to detect
      individuals driving under the influence of alcohol by measuring biological
      signals. We used the frequency time series analysis to attempt to distinguish
      between normal and intoxicated states of a person as the basis of the sensing
      system.

PMID- 21075733
TI  - Comparison of multiresolution features for texture classification of carotid
      atherosclerosis from B-mode ultrasound.
AB  - In this paper, a multiresolution approach is suggested for texture classification
      of atherosclerotic tissue from B-mode ultrasound. Four decomposition schemes,
      namely, the discrete wavelet transform, the stationary wavelet transform, wavelet
      packets (WP), and Gabor transform (GT), as well as several basis functions, were
      investigated in terms of their ability to discriminate between symptomatic and
      asymptomatic cases. The mean and standard deviation of the detail subimages
      produced for each decomposition scheme were used as texture features. Feature
      selection included 1) ranking the features in terms of their divergence values
      and 2) appropriately thresholding by a nonlinear correlation coefficient. The
      selected features were subsequently input into two classifiers using support
      vector machines (SVM) and probabilistic neural networks. WP analysis and the
      coiflet 1 produced the highest overall classification performance (90% for
      diastole and 75% for systole) using SVM. This might reflect WP's ability to
      reveal differences in different frequency bands, and therefore, characterize
      efficiently the atheromatous tissue. An interesting finding was that the dominant
      texture features exhibited horizontal directionality, suggesting that texture
      analysis may be affected by biomechanical factors (plaque strains).

PMID- 21075734
TI  - Feature selection and classification in supporting report-based self-management
      for people with chronic pain.
AB  - Chronic pain is a common long-term condition that affects a person's physical and
      emotional functioning. Currently, the integrated biopsychosocial approach is the
      mainstay treatment for people with chronic pain. Self-reporting (the use of
      questionnaires) is one of the most common methods to evaluate treatment outcome.
      The questionnaires can consist of more than 300 questions, which is tedious for
      people to complete at home. This paper presents a machine learning approach to
      analyze self-reporting data collected from the integrated biopsychosocial
      treatment, in order to identify an optimal set of features for supporting self
      management. In addition, a classification model is proposed to differentiate the
      treatment stages. Four different feature selection methods were applied to rank
      the questions. In addition, four supervised learning classifiers were used to
      investigate the relationships between the numbers of questions and classification
      performance. There were no significant differences between the feature ranking
      methods for each classifier in overall classification accuracy or AUC ( p >
      0.05); however, there were significant differences between the classifiers for
      each ranking method ( p < 0.001). The results showed the multilayer perceptron
      classifier had the best classification performance on an optimized subset of
      questions, which consisted of ten questions. Its overall classification accuracy
      and AUC were 100% and 1, respectively.

PMID- 21075735
TI  - Developing EMRs in developing countries.
AB  - Clinics in developing nations often use paper-based records that are hard to
      manage or are inefficient. Electronic medical records (EMR) systems could help
      increase the efficiency and efficacy of these clinics. Even though some EMR
      systems have been developed for developing countries, they lack customizability.
      This paper gives some background information about EMR systems: how they are used
      in developed countries, and how FileMaker, an off-the-shelf database software,
      could be used to rapidly deploy EMR systems in clinics and hospitals of
      developing countries. An existing EMR database developed by Banner Alzheimer's
      Institute serves as a proof of concept that FileMaker is a viable EMR solution.

PMID- 21075736
TI  - Effect of posture change on the geometric features of the healthy carotid
      bifurcation.
AB  - Segmented cross-sectional MRI images were used to construct 3-D virtual models of
      the carotid bifurcation in ten healthy volunteers. Geometric features, such as
      bifurcation angle, internal carotid artery (ICA) angle, planarity angle,
      asymmetry angle, tortuosity, curvature, bifurcation area ratio, ICA/common
      carotid artery (CCA), external carotid artery (ECA)/CCA, and ECA/ICA diameter
      ratios, were calculated for both carotids in two head postures: 1) the supine
      neutral position; and 2) the prone sleeping position with head rotation to the
      right ( ~ 80 degrees ). The results obtained have shown that head rotation causes
      1) significant variations in bifurcation angle [32% mean increase for the right
      carotid (RC) and 21% mean decrease for the left carotid (LC)] and internal
      carotid artery angle (97% mean increase for the RC, 43% mean decrease for the
      LC); 2) a slight increase in planarity and asymmetry angles for both RC and LC;
      3) minor and variable curvature changes for the CCA and for the branches; 4)
      slight tortuosity changes for the braches but not for the CCA; and 5)
      unsubstantial alterations in area and diameter ratios (percentage changes %). The
      significant geometric changes observed in most subjects with head posture may
      also cause significant changes in bifurcation hemodynamics and warrant future
      investigation of the hemodynamic parameters related to the development of
      atherosclerotic disease such as low oscillating wall shear stress and particle
      residence times.

PMID- 21075737
TI  - Use of an experimentally derived leadfield in the peripheral nerve pathway
      discrimination problem.
AB  - The task of discriminating the neural pathways responsible for the activity
      recorded using a multi-contact nerve cuff electrode has recently been approached
      as an inverse problem of source localization, similar to EEG source localization.
      A major drawback of this method is that it requires a model of the nerve, and
      that the localization performance is highly dependent on the accuracy of this
      model. Using recordings from a 56-contact "matrix" cuff electrode placed on a rat
      sciatic nerve, we investigated a method that eliminates the need for a model, and
      uses instead an "experimental" leadfield constructed from a training set of
      experimental recordings. The resulting pathway-identification task is solved
      using an inverse problem framework. The experimental leadfield approach was able
      to identify the correct branch in cases in which a single fascicle was active
      with a success rate of 94.2%, but was not able to reliably identify combinations
      of fascicles. Nevertheless, the proposed methodology provides a framework for the
      study of multi-pathway discrimination, within which methods to improve
      performance can be investigated. Specifically, the influence of nerve anatomy and
      electrode design should be examined, and regularization approaches better suited
      to this novel inverse problem should be sought.

PMID- 21075738
TI  - Pathological tremor and voluntary motion modeling and online estimation for
      active compensation.
AB  - This paper presents an algorithm to perform online tremor characterization from
      motion sensors measurements, while filtering the voluntary motion performed by
      the patient. In order to estimate simultaneously both nonstationary signals in a
      stochastic filtering framework, pathological tremor was represented by a time
      varying harmonic model and voluntary motion was modeled as an auto-regressive
      moving-average (ARMA) model. Since it is a nonlinear problem, an extended Kalman
      filter (EKF) was used. The developed solution was evaluated with simulated
      signals and experimental data from patients with different pathologies. Also, the
      results were comprehensively compared with alternative techniques proposed in the
      literature, evidencing the better performance of the proposed method. The
      algorithm presented in this paper may be an important tool in the design of
      active tremor compensation systems.

PMID- 21075739
TI  - Analysis of viscoelastic properties of wrist joint for quantification of
      parkinsonian rigidity.
AB  - This study aims to analyze viscoelastic properties of the wrist in patients with
      Parkinson's disease (PD) in comparison with the clinical score of severity. Forty
      five patients with PD and 12 healthy volunteers participated in this study.
      Severity of rigidity at the wrist was rated by a neurologist just before the
      experiment. Wrist joint torque resistive to the imposed movement was measured.
      Three different models, (identical in structure, only different in the number of
      parameters for extension and flexion phases) were used in identification of
      viscoelastic properties: 1) one damping constant and one spring constant
      throughout all phases, 2) two damping constants for each phase and one spring
      constant throughout all phases, and 3) two damping constants and two spring
      constants for each phase. Normalized work and impulse suggested in the literature
      were also calculated. Spring constants of different models and phases showed
      comparable correlation with rigidity score ( r=0.68-0.73). In terms of the
      correlation of damping constant with clinical rigidity score, model 1 ( r = 0.90)
      was better than models 2 and 3 ( r=0.59 - 0.71). These results suggest that the
      clinical rigidity score is better represented by the mean viscosity during both
      flexion and extension. In models with two dampers (model 2 and 3), the damping
      constant was greater during extension than flexion in patients , in contrast that
      there was no phase difference in normal subjects. This suggests that in contrast
      with normal subjects, phase-dependent viscosity may be an inherent feature of PD.
      Although work and impulse were correlated with clinical rigidity score ( r = 0.11
      - 0.84), they could not represent the phase-dependent rigidity inherent in PD. In
      conclusion, the viscosity of model 1 would be appropriate for quantification of
      clinical ratings of rigidity and that of model 2 for distinction of PD and also
      for investigation of phase-dependent characteristics in parkinsonian rigidity.

PMID- 21075740
TI  - Distinct cytokine profiles define clinical immune response to falciparum malaria
      in regions of high or low disease transmission.
AB  - The immune effector response to Plasmodium falciparum infection involves a finely
      tuned interplay between different cell types and cytokines. However, the
      processes by which they mediate the development of clinical immunity, in areas of
      different endemicity, are poorly understood. We analyzed circulating levels of
      pro-inflammatory (TNF, IFN-gamma, IL-12, IL-16) and anti-inflammatory (IL-4, IL
      10, IL-13) cytokines in control and patient groups drawn from a P. falciparum
      endemic and a non-endemic region of India. The endemic region control population
      exhibited a lower pro- to anti-inflammatory cytokine ratio, indicating a shift
      towards a high basal Th2 response. Levels of IL-10 contributed most towards the
      region-specific difference in basal cytokine response. IL-10 was also the
      strongest predictor of disease in the endemic region, while IL-12, along with IL
      10 and IL-6, contributed most to disease outcome in the non-endemic region. A
      low, mean IFN-gamma/IL-10 ratio was associated with disease severity in the
      endemic region (p < 0.0001). In contrast, a low mean IL-12/IL-10 ratio correlated
      with disease outcome in the non-endemic region (p < 0.0001). In the endemic
      region, IL-13 correlated negatively with IFN-gamma in severe patients (Spearman's
      rho: -0.49; p : 0.013), while in the non-endemic region, IL-13 correlated
      negatively with IL-6 in severe malaria patients (Spearman's rho: -0.485; p :
      0.001). In conclusion, levels of pro- and anti-inflammatory cytokines and the
      relative balance between the Th1 and Th2 response, illustrates how populations
      residing in areas of varying disease endemicity may respond to P. falciparum
      induced immune challenge.

PMID- 21075741
TI  - The uniqueome: a mappability resource for short-tag sequencing.
AB  - SUMMARY: Quantification applications of short-tag sequencing data (such as CNVseq
      and RNAseq) depend on knowing the uniqueness of specific genomic regions at a
      given threshold of error. Here, we present the 'uniqueome', a genomic resource
      for understanding the uniquely mappable proportion of genomic sequences. Pre
      computed data are available for human, mouse, fly and worm genomes in both color
      space and nucletotide-space, and we demonstrate the utility of this resource as
      applied to the quantification of RNAseq data. AVAILABILITY: Files, scripts and
      supplementary data are available from http://grimmond.imb.uq.edu.au/uniqueome/;
      the ISAS uniqueome aligner is freely available from http://www.imagenix.com/.

PMID- 21075742
TI  - Inference of gene networks--application to Bifidobacterium.
AB  - MOTIVATION: The reliable and reproducible identification of gene interaction
      networks represents one of the grand challenges of both modern molecular biology
      and computational sciences. Approaches based on careful collection of literature
      data and network topological analysis, applied to unicellular organisms, have
      proven to offer results applicable to medical therapies. However, when little a
      priori knowledge is available, other approaches, not relying so strongly on
      previous literature, must be used. We propose here a novel algorithm (based on
      ordinary differential equations) able to infer the interactions occurring among
      genes, starting from gene expression steady state data. RESULTS: The algorithm
      was first validated on synthetic and real benchmarks. It was then applied to the
      reconstruction of the core of the amino acids metabolism in Bifidobacterium
      longum, an essential, yet poorly known player in the human gut intestinal
      microbiome, known to be related to the onset of important diseases, such as
      metabolic syndromes. Our results show how computational approaches can offer
      effective tools for applications with the identification of potential new
      biological information. AVAILABILITY: The software is available at
      www.bioconductor.org and at www.picb.ac.cn/ClinicalGenomicNTW/temp2.html.

PMID- 21075743
TI  - Analyzing marginal cases in differential shotgun proteomics.
AB  - SUMMARY: We present an approach to statistically pinpoint differentially
      expressed proteins that have quantitation values near the quantitation threshold
      and are not identified in all replicates (marginal cases). Our method uses a
      Bayesian strategy to combine parametric statistics with an empirical distribution
      built from the reproducibility quality of the technical replicates. AVAILABILITY:
      The software is freely available for academic use at
      http://pcarvalho.com/patternlab.

PMID- 21075744
TI  - Evolutionary design principles and functional characteristics based on kingdom
      specific network motifs.
AB  - BACKGROUND: Network motifs within biological networks show non-random abundances
      in systems at different scales. Large directed protein networks at the cellular
      level are now well defined in several diverse species. We aimed to compare the
      nature of significantly observed two- and three-node network motifs across three
      different kingdoms (Arabidopsis thaliana for multicellular plants, Saccharomyces
      cerevisiae for unicellular fungi and Homo sapiens for animals). RESULTS: 'Two
      node feedback' is the most significant motif in all three species. By considering
      the sign of each two-node feedback interaction, we examined the enrichment of the
      three types of two-node feedbacks [positive-positive (PP), negative-negative (NN)
      and positive-negative (PN)]. We found that PN is enriched in the network of
      A.thaliana, NN in the network of S.cerevisiae and PP and NN in the network of
      H.sapiens. Each feedback type has characteristic features of robustness,
      multistability and homeostasis. CONCLUSIONS: We suggest that amplification of
      particular network motifs emerges from contrasting dynamical and topological
      properties of the motifs, reflects the evolutionary design principles selected by
      the characteristic behavior of each species and provides a signature pointing to
      their behavior and function.

PMID- 21075745
TI  - Protein Peeling 3D: new tools for analyzing protein structures.
AB  - We present an improved version of our Protein Peeling web server dedicated to the
      analysis of protein structure architecture through the identification of protein
      units produced by an iterative splitting algorithm. New features include
      identification of structural domains, detection of unstructured terminal elements
      and evaluation of the stability of protein unit structures. AVAILABILITY: The
      website is free and open to all users with no login requirements at
      http://www.dsimb.inserm.fr/dsimb-tools/peeling3.

PMID- 21075746
TI  - Assigning duplication events to relative temporal scales in genome-wide studies.
AB  - MOTIVATION: In genome-wide analyses, the relative age of gene duplications is
      often estimated by measuring the rate of synonymous substitutions (dS) between
      paralogous sequences. On the other hand, recent studies have shown the
      feasibility of inferring, at genomic scales, the relative age of duplication
      events from the topology of gene family trees. This represents a promising
      alternative for large surveys requiring an automatic methodology to establish a
      timeline of duplication events and that are usually limited to the use of dS,
      which presents known limitations such as a fast saturation of the signal.
      However, both measures have never been compared in a common framework. RESULTS:
      Topology-based placement of duplications on a relative time scale corresponding
      to periods between speciation events were found to be highly consistent,
      providing the same placement for 67-84% of a reliable set of gene pairs
      duplicated in a single event. For recent evolutionary periods, dS and topological
      measures showed a strong correlation. We conclude that the topology-based
      approach is more appropriate for assigning duplications to temporal scales when
      analyses need to include ancient events, and that the study of recent
      duplications may benefit from a combination of dS and topology information.

PMID- 21075747
TI  - QuACN: an R package for analyzing complex biological networks quantitatively.
AB  - MOTIVATION: Network-based representations of biological data have become an
      important way to analyze high-throughput data. To interpret the large amount of
      data that is produced by different high-throughput technologies, networks offer
      multifaceted aspects to analyze the data. As networks represent biological
      relationships within their structure, it turned out to be fruitful to analyze
      their topology. Therefore, we developed a freely available, open source R-package
      called Quantitative Analysis of Complex Networks (QuACN) to meet this challenge.
      QuACN contains different, information-theoretic and non-information-theoretic,
      topological network descriptors to analyze, classify and compare biological
      networks. AVAILABILITY: QuACN is freely available under LGPL via CRAN
      (http://cran.r-project.org/web/packages/QuACN/).

PMID- 21075748
TI  - Differential effects of chromatin regulators and transcription factors on gene
      regulation: a nucleosomal perspective.
AB  - MOTIVATION: Chromatin regulators (CR) and transcription factors (TF) are
      important trans-acting factors regulating transcription process, and many efforts
      have been devoted to understand their underlying mechanisms in gene regulation.
      However, the influences of CR and TF regulation effects on nucleosomes during
      transcription are still minimally understood, and it remains to be determined the
      extent to which CR and TF regulatory effect shape the organization of nucleosomes
      in the genome. In this article we attempted to address this problem and examine
      the patterns of CR and TF regulation effects from the nucleosome perspective.
      RESULTS: Our results show that the CR and TF regulatory effects exhibit different
      paradigms of transcriptional control in Saccharomyces cerevisiae. We grouped
      yeast genes into two categories, 'CR-sensitive' genes and 'TF-sensitive' genes,
      based on how their expression profiles change upon deletion of CRs or TFs. We
      found that genes in these two groups have very different patterns of nucleosome
      organization. The promoters of CR-sensitive genes tend to have higher nucleosome
      occupancy, whereas the promoters of TF-sensitive genes are depleted of
      nucleosomes. Furthermore, the nucleosome profiles of CR-sensitive genes tend to
      show more dynamic characteristics than TF-sensitive genes. These results reveal
      that the nucleosome organizations of yeast genes have a strong impact on their
      mode of regulation, and there are differential regulation effects on nucleosomes
      between CRs and TFs. AVAILABILITY:
      http://www.utoronto.ca/zhanglab/papers/bioinfo_2010/.

PMID- 21075749
TI  - TE Displayer for post-genomic analysis of transposable elements.
AB  - SUMMARY: TE Displayer can be used to retrieve genetic polymorphisms caused by
      transposable elements (TEs) in large-genomic datasets and present the results on
      virtual gel images. This enables researchers to compare TE profiles in silico and
      provides reference profiles for experimental analyses. AVAILABILITY AND
      IMPLEMENTATION: Freely available on the web at
      http://labs.csb.utoronto.ca/yang/TE_Displayer.

PMID- 21075750
TI  - Electronic medical records, nurse staffing, and nurse-sensitive patient outcomes:
      evidence from the national database of nursing quality indicators.
AB  - Electronic medical records (EMR) have the potential to improve nursing care in
      the hospital setting. This study estimated the association of EMR implementation
      with nurse staffing levels, skill mix, contract/agency percent, and nurse
      sensitive patient outcomes in U.S. hospitals. Data on nurse staffing and patient
      outcomes came from the 2004-2008 National Database of Nursing Quality Indicators.
      Data on EMR implementation came from the 2004-2008 HIMSS Analytics Database. The
      authors conducted a longitudinal analysis of an unbalanced panel of 3,048
      medical/surgical units in 509 short-term, general acute care hospitals. EMR
      implementation was associated with lower total nurse hours per patient day,
      higher Registered Nurse percent and contract/agency percent, and higher adverse
      patient events in the short term. EMR may create a skill bias toward higher
      skilled nurses. As more advanced EMR systems diffuse into practice, managers and
      policy makers should consider potential negative associations of EMR
      implementation with patient safety.

PMID- 21075751
TI  - Translating frontiers into practice: taking the next steps toward improving
      hospital efficiency.
AB  - Frontier techniques, including data envelopment analysis (DEA) and stochastic
      frontier analysis (SFA), have been used to measure health care provider
      efficiency in hundreds of published studies. Although these methods have the
      potential to be useful to decision makers, their utility is limited by both
      methodological questions concerning their application, as well as some disconnect
      between the information they provide and the insight sought by decision makers.
      The articles in this special issue focus on the application of DEA and SFA to
      hospitals with the hope of making these techniques more accurate and accessible
      to end users. This introduction to the special issue highlights the importance of
      measuring the efficiency of health care providers, provides a background on
      frontier techniques, contains an overview of the articles in the special issue,
      and suggests a research agenda for DEA and SFA.

PMID- 21075752
TI  - Qualitative methods: a crucial tool for understanding changes in health systems
      and health care delivery.

PMID- 21075753
TI  - Measuring shared inefficiency between hospital cost centers.
AB  - In this article, a combination of data envelopment analysis, spreadsheet modeling
      and regression techniques is applied to a panel of nonprofit Washington State
      hospitals in an effort to determine whether (and if so, to what extent)
      inefficiency in one hospital cost center is shared with inefficiency in other
      cost centers. The findings suggest that a significant amount of inefficiency is
      shared across hospital cost centers. The authors further determine that certain
      cost centers contribute more to the overall performance of a given hospital than
      others. As such, managerial decisions and government policies designed to enhance
      hospital efficiency should be implemented differently, depending on the
      characteristics of the hospital in question.

PMID- 21075754
TI  - The current state of practice in the diagnosis of venous thromboembolism at an
      academic medical center.
AB  - Evidence-based guidelines for the diagnosis of venous thromboembolism (VTE) have
      been recommended, yet the adoption of such guidelines into daily practice is
      unknown. The purpose of this study was to describe the current practices in the
      diagnosis of VTE. Medical records of 1161 adult patients who underwent lower
      extremity venous duplex scans (VDS), chest computerized tomographic (CT)
      angiography, or ventilation and perfusion (V/Q) scans during a 6-month period
      were retrospectively reviewed in an academic medical center. Patients who were
      first diagnosed by CT or V/Q scan still underwent a VDS. Nine patients at high
      risk had incomplete CT scans, yet no further tests were performed. Five pregnant
      patients had CT scans as the initial test instead of being screened with VDS or
      V/Q scanning. Inappropriate use of imaging tests was documented. The recommended
      guidelines of using clinical probability and D-dimer as the initial screening
      tests for VTE diagnosis were underused.

PMID- 21075755
TI  - Arc of Buhler aneurysm: a rare cause of obstructive jaundice.

PMID- 21075756
TI  - Mechanisms of atrial structural changes caused by stretch occurring before and
      during early atrial fibrillation.
AB  - Structural remodelling occurring before, due to the underlying heart disease, and
      during atrial fibrillation (AF) sets the stage for permanent AF. Current therapy
      in AF aims to maintain sinus rhythm in symptomatic patients, but outcome is
      unfortunately poor. Stretch of the atria is a main contributor to atrial
      remodelling. In this review, we describe different aspects of structural
      remodelling as seen in animal models and in patients with AF, including atrial
      enlargement, cellular hypertrophy, dedifferentiation, fibrosis, apoptosis, and
      loss of contractile elements. In the second part, we describe downstream signals
      of mechanical stretch and their contribution to AF and structural remodelling.
      Ultimately, knowledge of mechanisms underlying structural remodelling may help to
      identify new pharmacological targets for AF prevention.

PMID- 21075757
TI  - Comparison of skin adhesive and absorbable intracutaneous suture for the
      implantation of cardiac rhythm devices.
AB  - AIMS: Wound healing is a major determent in the post-surgical course of patients
      (pts) after pacemaker (PM) and implantable cardioverter defibrillator (ICD)
      implantation. Insufficient closure may lead to serious complications with pocket
      infections leading to the device's explantation as the worst case scenario. In
      addition to the different types of suture and suture clips, a novel topical skin
      adhesive containing 2-octyl-cyanoacrylate is commercially available. METHODS AND
      RESULTS: Over a period of 18 months, we prospectively assigned all cases of PM,
      ICD, and loop recorder implants either to skin adhesive (Group 1) or to
      absorbable intracutaneous polydioxanon suture (Group 2). Data were analysed with
      respect to operation time, wound infections, and healing disorders. One hundred
      and eighty-three pts were randomized into Group 1 [71 PMs, 60 ICD, 15 cardiac
      resynchronization therapy (CRT), 11 loop recorders, and 26 generator
      replacements]. One hundred and eighty-five pts were assigned to Group 2 (62 PMs,
      70 ICD, 30 CRT, 7 loop recorders, and 16 generator replacements). There were no
      differences regarding sex, diabetes, renal insufficiency, corticosteroid therapy,
      oral anticoagulants, and acetylsalicylic asa/clopidogrel (P = n.s.). For the
      significantly higher amount of CRT devices (P < 0.05) in Group 2, the procedure
      times are given for surgeries except CRT. It was 49.1 +/- 27.7 min for Group 1
      and 53.4 +/- 31.9 min for Group 2 (P = n.s.). Adverse events as insufficient
      closure, major and minor bleeding, pocket haematoma, erythema, incrustation,
      dehiscence, keloid, and explantation due to infection occurred significantly more
      often in the adhesive group (P = 0.02). The greatest impact on this result had
      early adverse events as insufficient closure, wound incrustation, and
      inflammation (9.3 vs. 6.0%; P = 0.02). We did not find any difference in long
      term adverse events, infections in particular (2.7 vs. 1.6%; P = 0.47).
      CONCLUSION: This study shows no benefit using skin adhesive in comparison to
      absorbable intracutaneous suture regarding surgery times for the implantation of
      cardiac rhythm devices. The rate of early adverse events after wound closure is
      higher after skin adhesive but no difference in long-term adverse events
      occurred.

PMID- 21075758
TI  - Ablation of a right-sided accessory pathway with the Hansen robotic system.

PMID- 21075759
TI  - Changing QRS morphology during catheter ablation of outflow tract ventricular
      tachycardia: what is the mechanism?
AB  - A 62-year-old male patient underwent catheter ablation for outflow tract
      ventricular tachycardia (VT). During radiofrequency catheter ablation in the
      right ventricular outflow tract, the VT morphology abruptly changed and its exit
      shifted to the left coronary cusp. Ablation at this site terminated the VT and
      rendered it non-inducible. Accurate analysis of the 12-lead ECG during catheter
      ablation may reveal VT exit shift as a possible explanation for unsuccessful
      catheter ablation of outflow tract VT.

PMID- 21075760
TI  - Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base
      deletion in CSF2RB.
AB  - BACKGROUND: Disruption of granulocyte/macrophage colony-stimulating factor (GM
      CSF) signalling causes pulmonary alveolar proteinosis (PAP). Rarely, genetic
      defects in neonatal or infant-onset PAP have been identified in CSF2RA. However,
      no report has clearly identified any function-associated genetic defect in
      CSF2RB. METHODS AND RESULTS: The patient was diagnosed with PAP at the age of 36
      and developed respiratory failure. She was negative for GM-CSF autoantibody and
      had no underlying disease. Signalling and genetic defects in GM-CSF receptor were
      screened. GM-CSF-stimulated STAT5 phosphorylation was not observed and GM-CSF
      Rbetac expression was defective in the patient's blood cells. Genetic screening
      revealed a homozygous, single-base deletion at nt 631 in exon 6 of CSF2RB on
      chromosome 22, which caused reductions in GM-CSF dependent signalling and
      function. Both parents, who were second cousins, showed no pulmonary symptoms,
      and had normal GM-CSF-signalling, but had a CSF2RB allele with the identical
      deletion, indicating that the mutant allele may give rise to PAP in an autosomal
      recessive manner. CONCLUSIONS: This is the first report identifying a genetic
      defect in CSF2RB that causes deficiency of GM-CSF-Rbetac expression and impaired
      signalling downstream. These results suggested that GM-CSF signalling was
      compensated by other signalling pathways, leading to adult-onset PAP.

PMID- 21075761
TI  - Chromosomal aberration analysis among underground water well workers in Saudi
      Arabia.
AB  - In the absence of permanent rivers or bodies of water, half of the Saudi Arabia
      domestic water consumption is provided through desalination. The other half is
      derived from groundwater. Groundwater from the Disi aquifer is already used for
      drinking water in parts of Jordan and, more extensively, in Saudi Arabia, where
      it is known as the Saq aquifer. Some of the geological analyses of the host
      sandstone aquifer rocks show (228)Ra and (226)Ra. The usefulness of chromosomal
      aberrations analysis as a bioindicator for ionising radiation effect was tested
      in underground water well workers of Saudi Arabia in this industry producing
      technologically enhanced naturally occurring radioactive material. The incidence
      of chromosomal aberrations was evaluated using the metaphase analysis method in
      the lymphocytes of peripheral blood of 10 persons working in underground water
      well. The age range of the workers was 25-40 y and their duration of service
      ranged from 3-7 y. For comparison, blood samples were also collected from 10
      subjects (controls) who belonged to same age and socioeconomic status. Subjects
      in the both groups were non-smokers and non-alcoholics. Results showed that the
      mean frequencies of dicentrics and acentrics in underground water well workers
      are significantly higher than those in controls. The higher frequency of
      chromosomal aberration in lymphocytes of underground water well workers compared
      with controls could be due to the accumulative effect of radiation. The results
      of this study demonstrated that occupational exposure to radiation leads to a
      significant induction of cytogenetic damage in peripheral lymphocytes of workers
      engaged in underground water well.

PMID- 21075762
TI  - Calculation of the uncertainty in the activity estimate for workers in the
      uranium industry.
AB  - This paper describes a methodology to calculate the uncertainty that may
      propagate during the uranium activity estimation for workers. An analytical
      expression was derived to find a relationship between measured activity and the
      chest wall thickness that is routinely measured for workers. The uncertainty in
      activity estimation was empirically calculated for 14 workers using their
      measured chest wall thicknesses collected over a 5 y time period.

PMID- 21075763
TI  - Metabolism of 210Po in rats: volatile 210Po from faeces.
AB  - The metabolic formation of volatile (210)Po species in a rat that was
      intravenously administered with (210)Po-citrate was investigated in this study. A
      slurry of the faecal sample was prepared in water and was bubbled with nitrogen
      gas in a closed system. The discharged gas was passed through a trapping device
      filled with liquid scintillation cocktail in order to capture any volatile
      (210)Po species. The amount of (210)Po trapped in the scintillation cocktail was
      measured by a liquid scintillation analyser that provided evidence of the
      presence of volatile (210)Po species in the faeces. The presence of volatile
      (210)Po in the faeces indicates that the metabolic formation of volatile (210)Po
      is likely to occur in the gut due to bacterial activity. The amount of volatile
      (210)Po species was compared with the daily faecal excretion of (210)Po. After 2
      h of bubbling, the volatile (210)Po collected from the faeces sample was found to
      be between 1.0 and 1.7 % of the daily faecal excretion for the 4 d following
      (210)Po-citrate administration.

PMID- 21075764
TI  - A generic biokinetic model for Carbon-14.
AB  - The generic biokinetic model currently recommended by the International
      Commission on Radiological Protection (ICRP) for the treatment of systemic
      radiocarbon assumes uniform distribution of activity in tissues and a biological
      half-time of 40 d. This model is intended to generate cautiously high estimates
      of dose per unit intake of C-14 and, in fact, generally predicts a much higher
      effective dose than systemic models that have been developed on the basis of
      biokinetic studies of specific carbon compounds. The simplistic model formulation
      precludes its application as a bioassay model or adjustment to fit case-specific
      bioassay data. This paper proposes a new generic biokinetic model for systemic
      radiocarbon that is less conservative than the current ICRP model but maintains
      sufficient conservatism to overestimate the effective dose coefficients generated
      by most radiocarbon-compound-specific models. The proposed model includes two
      systemic pools with different biological half-times representing an initial
      systemic form of absorbed radiocarbon, a submodel describing the behaviour of
      labelled carbon dioxide produced in vivo, and three excretion pathways: breath,
      urine and faeces. Generic excretion rates along each path are based on multi
      phase excretion curves observed in experimental studies of radiocarbons. The
      generic model structure is designed so that the user may adjust the level of
      dosimetric conservatism to fit the information at hand and may adjust parameter
      values for consistency with subject-specific or site-specific bioassay data.

PMID- 21075765
TI  - Quality management system and accreditation of the in vivo monitoring laboratory
      at Karslruhe Institute of Technology.
AB  - The in vivo monitoring laboratory (IVM) at Karlsruhe Institute of Technology
      (KIT), with one whole body counter and three partial-body counters, is an
      approved lab for individual monitoring according to German regulation. These
      approved labs are required to prove their competencies by accreditation to
      ISO/IEC 17025:2005. In 2007 a quality management system (QMS), which was
      successfully audited and granted accreditation, was set up at the IVM. The system
      is based on the ISO 9001 certified QMS of the central safety department of the
      Research Centre Karlsruhe the IVM belonged to at that time. The system itself was
      set up to be flexible and could be adapted to the recent organisational changes
      (e.g. founding of KIT and an institute for radiation research) with only minor
      effort.

PMID- 21075766
TI  - The ghost of methods past: exposure assessment versus job-exposure matrix
      studies.

PMID- 21075767
TI  - Impact of common mental disorders on sickness absence in an occupational cohort
      study.
AB  - OBJECTIVES: Common mental disorders are associated with impaired functioning and
      sickness absence. We examine whether sub-clinical as well as clinical psychiatric
      morbidity predict long spells of sickness absence for both psychiatric and non
      psychiatric illness. We also examine whether recent common mental disorders and
      those present on two occasions have a stronger association with sickness absence
      than less recent and single episodes of disorder. METHODS: Common mental
      disorders measured by the General Health Questionnaire were linked with long
      spells of sickness absence in 5104 civil servants from the longitudinal Whitehall
      II Study. Negative binomial models were used to estimate rate ratios for long
      spells of sickness absence with and without a psychiatric diagnosis (mean follow
      up 5.3 years). RESULTS: Clinical but not sub-threshold common mental disorders
      were associated with increased risk of long spells of psychiatric sickness
      absence for men, but not for women, after adjusting for covariates (rate ratios
      (RR) 1.67, 95% CI 1.13 to 2.46). Risk of psychiatric sickness absence was
      associated with recent common mental disorders (RR 2.08, 95% CI 1.29 to 3.35) and
      disorder present on two occasions (RR 1.65, 95% CI 0.98 to 2.71) for men only.
      Common mental disorders were not associated with increased risk of non
      psychiatric sickness absence after adjustment for covariates. CONCLUSIONS:
      Identification and treatment of common mental disorders may reduce the economic
      burden of long term psychiatric sickness absence. Our results suggest that public
      health and clinical services should focus on the identification of workers with
      elevated mental health symptoms. Studies are needed of the efficacy of early
      identification and management of mental health symptoms for the prevention of
      long spells of sickness absence.

PMID- 21075768
TI  - Translation of mechanical exposure in the workplace into common metrics for meta
      analysis: a reliability and validity study.
AB  - OBJECTIVES: We previously assessed inter-rater reliability of expert raters using
      six scales to estimate the intensity of literature-based mechanical exposures.
      The objectives of this study were to estimate the impact on the inter-rater
      reliability of using non-expert (NE) raters and to assess the validity of our
      scales. METHODS: We used 7-point scales to represent three dimensions of
      mechanical exposures at work: 1) trunk posture, 2) weight lifted or force exerted
      and 3) spinal loading. We estimated both peak and cumulative loads and called
      this an "interpretive translation" of exposure. A second method, "algorithmic
      translation", used the original units in which the exposure data was collected.
      These data were used to assess the inter-rater reliability and validity of the NE
      interpretive translation of exposure. RESULTS: The NE inter-rater reliability for
      the scales ranged from 0.24 to 0.46. The correlation between the means of the NE
      and expert ratings were >0.7. Although there was a strong relationship between
      the NE interpretive and the algorithmic translation, there was some evidence that
      the interpretive translation plateaus at higher level of exposure. CONCLUSIONS:
      This study supports using NE raters to estimate the intensity of literature-based
      mechanical exposure metrics using a common set of scales which can be applied
      across epidemiologic studies. We would need to average the ratings of at least
      five NE raters to have an acceptable level of reliability (>0.7). These metrics
      may be useful to quantify the relationship between workplace mechanical exposure
      and low back pain in a systematic review and meta-analysis.

PMID- 21075770
TI  - Noncanonical translation initiation of the Arabidopsis flowering time and
      alternative polyadenylation regulator FCA.
AB  - The RNA binding protein FCA regulates the floral transition and is required for
      silencing RNAs corresponding to specific noncoding sequences in the Arabidopsis
      thaliana genome. Through interaction with the canonical RNA 3' processing
      machinery, FCA affects alternative polyadenylation of many transcripts, including
      antisense RNAs at the locus encoding the floral repressor FLC. This potential for
      widespread alteration of gene regulation clearly needs to be tightly regulated,
      and we have previously shown that FCA expression is autoregulated through poly(A)
      site choice. Here, we show distinct layers of FCA regulation that involve
      sequences within the 5' region that regulate noncanonical translation initiation
      and alter the expression profile. FCA translation in vivo occurs exclusively at a
      noncanonical CUG codon upstream of the first in-frame AUG. We fully define the
      upstream flanking sequences essential for its selection, revealing features that
      distinguish this from other non-AUG start site mechanisms. Bioinformatic analysis
      identified 10 additional Arabidopsis genes that likely initiate translation at a
      CUG codon. Our findings reveal further unexpected complexity in the regulation of
      FCA expression with implications for its roles in regulating flowering time and
      gene expression and more generally show plant mRNA exceptions to AUG translation
      initiation.

PMID- 21075771
TI  - Screening for obstructive sleep apnea by cyclic variation of heart rate.
AB  - BACKGROUND: Despite the adverse cardiovascular consequences of obstructive sleep
      apnea, the majority of patients remain undiagnosed. To explore an efficient ECG
      based screening tool for obstructive sleep apnea, we examined the usefulness of
      automated detection of cyclic variation of heart rate (CVHR) in a large-scale
      controlled clinical setting. METHODS AND RESULTS: We developed an algorithm of
      autocorrelated wave detection with adaptive threshold (ACAT). The algorithm was
      optimized with 63 sleep studies in a training cohort, and its performance was
      confirmed with 70 sleep studies of the Physionet Apnea-ECG database. We then
      applied the algorithm to ECGs extracted from all-night polysomnograms in 862
      consecutive subjects referred for diagnostic sleep study. The number of CVHR per
      hour (the CVHR index) closely correlated (r=0.84) with the apnea-hypopnea index,
      although the absolute agreement with the apnea-hypopnea index was modest (the
      upper and lower limits of agreement, 21 per hour and -19 per hour) with periodic
      leg movement causing most of the disagreement (P<0.001). The CVHR index showed a
      good performance in identifying the patients with an apnea-hypopnea index >=15
      per hour (area under the receiver-operating characteristic curve, 0.913; 83%
      sensitivity and 88% specificity, with the predetermined cutoff threshold of CVHR
      index >=15 per hour). The classification performance was unaffected by older age
      (>=65 years) or cardiac autonomic dysfunction (SD of normal-to-normal R-R
      intervals over the entire length of recording <65 ms; area under the receiver
      operating characteristic curve, 0.915 and 0.911, respectively). CONCLUSIONS: The
      automated detection of CVHR with the ACAT algorithm provides a powerful ECG-based
      screening tool for moderate-to-severe obstructive sleep apnea, even in older
      subjects and in those with cardiac autonomic dysfunction.

PMID- 21075769
TI  - Altered xylem-phloem transfer of amino acids affects metabolism and leads to
      increased seed yield and oil content in Arabidopsis.
AB  - Seed development and nitrogen (N) storage depend on delivery of amino acids to
      seed sinks. For efficient translocation to seeds, amino acids are loaded into the
      phloem in source leaves and along the long distance transport pathway through
      xylem-phloem transfer. We demonstrate that Arabidopsis thaliana AMINO ACID
      PERMEASE2 (AAP2) localizes to the phloem throughout the plant. AAP2 T-DNA
      insertion lines showed changes in source-sink translocation of amino acids and a
      decrease in the amount of seed total N and storage proteins, supporting AAP2
      function in phloem loading and amino acid distribution to the embryo.
      Interestingly, in aap2 seeds, total carbon (C) levels were unchanged, while fatty
      acid levels were elevated. Moreover, branch and silique numbers per plant and
      seed yield were strongly increased. This suggests changes in N and C delivery to
      sinks and subsequent modulations of sink development and seed metabolism. This is
      supported by tracer experiments, expression studies of genes of N/C transport and
      metabolism in source and sink, and by phenotypic and metabolite analyses of aap2
      plants. Thus, AAP2 is key for xylem to phloem transfer and sink N and C supply;
      moreover, modifications of N allocation can positively affect C assimilation and
      source-sink transport and benefit sink development and oil yield.

PMID- 21075772
TI  - Yeast hexokinase isoenzyme ScHxk2: stability of a two-domain protein with
      discontinuous domains.
AB  - The hexokinase isoenzyme 2 of Saccharomyces cerevisiae (ScHxk2) represents an
      archetype of a two-domain protein with the active site located in a cleft between
      the two domains. Binding of the substrate glucose results in a rigid body
      movement of the two domains leading to a cleft closure of the active site. Both
      domains of this enzyme are composed of discontinuous peptide sequences. This
      structural feature is reflected in the stability and folding of the ScHxk2
      protein. Structural transitions induced by urea treatment resulted in the
      population of a thermodynamically stable folding intermediate, which, however,
      does not correspond to a molecule with one domain folded and the other unfolded.
      As demonstrated by different spectroscopic techniques, both domains are
      structurally affected by the partial denaturation. The intermediate possesses
      only 40% of the native secondary structural content and a substantial increase in
      the Stokes radius as judged by circular dichroism and dynamic light scattering
      analyses. One-dimensional 1H NMR data prove that all tryptophan residues are in a
      non-native environment in the intermediate, indicating substantial changes in the
      tertiary structure. Still, the intermediate possesses quite a high stability for
      a transition intermediate of about DeltaG = -22 kJ mol-1.

PMID- 21075773
TI  - Time-dependent benefit of preventive cardiac resynchronization therapy after
      myocardial infarction.
AB  - AIMS: Cardiac remodelling is a progressive process after myocardial infarction
      (MI). However, currently there are no data regarding the effect of s:elapsed time
      from MI on the benefit of cardiac resynchronization therapy with defibrillator
      (CRT-D). The present study was designed to evaluate the relationship between
      elapsed time from MI and the benefit of preventive CRT-D therapy in patients with
      ischaemic cardiomyopathy (ICM). METHODS AND RESULTS: The risk of heart failure
      (HF) or death as a function of elapsed time from MI to enrolment, by treatment
      with CRT-D vs. implantable cardioverter defibrillator (ICD)-only therapy, was
      assessed among 704 ICM patients with a documented MI enrolled in MADIT-CRT, and
      separately in a subset of ICM patients without a documented prior MI (n = 237).
      In ICD patients, the adjusted risk of HF or death increased by 4% (P = 0.01) for
      each year elapsed from MI. Multivariate analysis demonstrated that patients with
      remote MI [categorized at the median value (>=8 years)] derived a significantly
      greater benefit from CRT-D [HR = 0.42 (P < 0.001)] than those with a more recent
      MI [HR = 1.26 (P = 0.35); P-value for interaction <0.001]. Consistently, the
      benefit of CRT-D was directly related to increasing quartiles of elapsed time
      from MI [Q(1) (<3 years): HR = 1.67; P = 0.20, Q(2) (3-8 years): HR = 1.12; P =
      0.71, Q(3) (8-15 years): HR = 0.47; P = 0.02, and Q(4) (>=15 years): HR = 0.38; P
      = 0.001]. The ICM subgroup with no documented MI also derived enhanced benefit
      from CRT-D (HR = 0.43; P = 0.003). CONCLUSION: In patients with ischaemic
      cardiomyopathy, the risk of HF or death and the magnitude of CRT-D benefit are
      directly related to elapsed time from MI.

PMID- 21075774
TI  - Response to preventive cardiac resynchronization therapy in patients with
      ischaemic and nonischaemic cardiomyopathy in MADIT-CRT.
AB  - AIMS: There are no data regarding the differential response to cardiac
      resynchronization therapy with defibrillator (CRT-D) by the aetiology of
      cardiomyopathy in mildly symptomatic patients. We evaluated the outcome of
      patients enrolled in MADIT-CRT by ischaemic and non-ischaemic aetiology of
      cardiomyopathy (ICM and non-ICM, respectively). METHODS AND RESULTS: The clinical
      response to CRT-D was assessed among ICM (n = 1046) and non-ICM (n = 774)
      patients enrolled in MADIT-CRT during an average follow-up of 2.4 years, and
      echocardiographic response was assessed at 1 year. Cardiac resynchronization
      therapy with defibrillator vs. ICD therapy was associated with respective 34% (P
      = 0.001) and 44% (P = 0.002) reductions in the risk of heart failure or death
      among ICM and non-ICM patients (P for interaction = 0.455). In the ICM group, CRT
      D was associated with mean (+/-SD) 29 +/- 14% and 18 +/- 10% reductions in left
      ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume
      (LVEDV), respectively. In the non-ICM group, CRT-D was associated with
      significantly greater volume reductions compared with the ICM group [37 +/- 16%
      and 24 +/- 12% reductions in LVESV and LVEDV, respectively (P < 0.001 for all)].
      Risk subsets in the ICM group that showed a favourable clinical response to CRT-D
      included patients with QRS >=150 ms, systolic blood pressure <115 mmHg, and left
      bundle branch block (LBBB), whereas in the non-ICM group females, patients with
      diabetes mellitus, and LBBB, displayed a favourable clinical response.
      CONCLUSION: Mildly symptomatic ICM and non-ICM patients show significant
      differences in the echocardiographic response to CRT-D and in the clinical
      benefit within risk subsets suggesting that risk assessment for CRT-D in this
      population should be aetiology-specific.

PMID- 21075775
TI  - One year follow-up of the multi-centre European PARTNER transcatheter heart valve
      study.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as a new
      therapeutic option in high-risk patients with severe aortic stenosis. AIMS:
      PARTNER EU is the first study to evaluate prospectively the procedural and mid
      term outcomes of transfemoral (TF) or transapical (TA) implantation of the
      Edwards SAPIEN(r) valve involving a multi-disciplinary approach. METHODS AND
      RESULTS: Primary safety endpoints were 30 days and 6 months mortality. Primary
      efficacy endpoints were haemodynamic and functional improvement at 12 months. One
      hundred and thirty patients (61 TF, 69 TA), aged 82.1 +/- 5.5 years were
      included. TA patients had higher logistic EuroSCORE (33.8 vs. 25.7%, P = 0.0005)
      and more peripheral disease (49.3 vs. 16.4%, P< 0.0001). Procedures were aborted
      in four TA (5.8%) and six TF cases (9.8%). Valve implantation was successful in
      the remaining patients in 95.4 and 96.4%, respectively. Thirty days and 6 months
      survival were 81.2 and 58.0% (TA) and 91.8 and 90.2% (TF). In both groups, mean
      aortic gradient decreased from 46.9 +/- 18.1 to 10.9 +/- 5.4 mmHg 6 months post
      TAVI. In total, 78.1 and 84.8% of patients experienced significant improvement in
      New York Heart Association (NYHA) class, whereas 73.9 and 72.7% had improved
      Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in TA and TF cohorts,
      respectively. CONCLUSION: This first team-based multi-centre European TAVI
      registry shows promising results in high-risk patients treated by TF or TA
      delivery. Survival rates differ significantly between TF and TA groups and
      probably reflect the higher risk profile of the TA cohort. Optimal patient
      screening, approach selection, and device refinement may improve outcomes.

PMID- 21075776
TI  - Acidosis, non-invasive ventilation and mortality in hospitalised COPD
      exacerbations.
AB  - BACKGROUND: Reports of non-invasive ventilation (NIV) use in clinical practice
      reveal higher mortality rates than in corresponding randomised clinical trials.
      AIM: To explore factors related to chronic obstructive pulmonary disease (COPD)
      admissions and NIV use that may explain some of the previously reported high
      mortality rates. METHODS: National UK audit of clinical care of consecutive COPD
      admissions from March to May 2008. Retrospective case note audit with prospective
      case ascertainment. Participating units completed a web-based audit proforma of
      process and outcomes of clinical care. RESULTS: 232 hospital units collected data
      on 9716 patients, mean age 73, 50% male. 1678 (20%) of those with gases recorded
      on admission were acidotic and another 6% became acidotic later. 1077 patients
      received NIV, 55% had a pH<7.26 and 49% (305/618) had or were still receiving
      high flow oxygen. 30% (136/453) patients with persisting respiratory acidosis did
      not receive NIV while 11% (15/131) of acidotic admissions had a pure metabolic
      acidosis and did. Hospital mortality was 25% (270/1077) for patients receiving
      NIV but 39% (86/219) for those with late onset acidosis and was higher in all
      acidotic groups receiving NIV than those treated without. Only 4% of patients
      receiving NIV who died had invasive mechanical ventilation. CONCLUSIONS: COPD
      admissions treated with NIV in usual clinical practice were severely ill, many
      with mixed metabolic acidosis. Some eligible patients failed to receive NIV,
      others received it inappropriately. NIV appears to be often used as a ceiling of
      treatment including patient groups in whom efficacy of NIV is uncertain. The
      audit raises concerns that challenge the respiratory community to lead
      appropriate clinical improvements across the acute sector.

PMID- 21075777
TI  - A case of pulmonary typical carcinoid with an extensive oncocytic component
      showing intense uptake of FDG.

PMID- 21075779
TI  - Usefulness of MS-MLPA for detection of MGMT promoter methylation in the
      evaluation of pseudoprogression in glioblastoma patients.
AB  - Pseudoprogression is a major diagnostic dilemma in current treatment protocols
      for malignant gliomas that involve concurrent chemoradiotherapy. We hypothesized
      that methylation-specific multiplex ligation probe amplification (MS-MLPA), an
      assay that permits semiquantitative evaluation of promoter methylation, may be
      used to diagnose pseudoprogression based on the quantification of the methylation
      status of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter. We
      examined the methylation ratio of the MGMT promoter with MS-MLPA in 48 samples
      from glioblastoma patients. The results were compared with those from methylation
      specific polymerase chain reaction (MSP), and protein levels were confirmed by
      immunohistochemical staining. We then evaluated the correlation between those
      molecular signatures and clinical outcomes. With regard to radiological
      progression after chemoradiotherapy, the diagnostic accuracy of the MS-MLPA
      method was 80% (using a cut-off value of 0.2). These results are better than
      those obtained with MSP (diagnostic accuracy of 68%). Combining the MS-MLPA and
      MSP methods resulted in a diagnostic accuracy of 93% for the identification of
      pseudoprogression among patients to whom these results were coherent. These
      results demonstrate that MS-MLPA is a useful method to predict radiological
      progression vs pseudoprogression in glioblastoma patients and that the
      interpretation of these results in combination with MSP results will provide good
      practical guidelines for clinical decision making in glioblastoma treatment.

PMID- 21075780
TI  - A single intravenous injection of oncolytic picornavirus SVV-001 eliminates
      medulloblastomas in primary tumor-based orthotopic xenograft mouse models.
AB  - Difficulties of drug delivery across the blood-brain barrier (BBB) and failure to
      eliminate cancer stem cells (CSCs) are believed to be the major causes of tumor
      recurrences in children with medulloblastoma (MB). Seneca Valley virus-001 (SVV
      001) is a naturally occurring oncolytic picornavirus that can be systemically
      administered. Here, we report its antitumor activities against MB cells in a
      panel of 10 primary tumor-based orthotopic xenograft mouse models. We found that
      SVV-001 killed the primary cultured xenograft cells, infected and replicated in
      tumor cells expressing CSC surface marker CD133, and eliminated tumor cells
      capable of forming neurospheres in vitro in 5 of the 10 xenograft models. We
      confirmed that SVV-001 could pass through BBB in vivo. A single i.v. injection of
      SVV-001 in 2 anaplastic MB models led to widespread infection of the preformed
      intracerebellar (ICb) xenografts, resulting in significant increase in survival
      (2.2-5.9-fold) in both models and complete elimination of ICb xenografts in 8 of
      the 10 long-term survivors. Mechanistically, we showed that the intracellular
      replication of SVV-001 is mediated through a subverted autophagy that is
      different from the bona fide autophagic process induced by rapamycin. Our data
      suggest that SVV-001 is well suited for MB treatment. This work expands the
      current views in the oncolytic therapy field regarding the utility of oncolytic
      viruses in simultaneous targeting of stem and nonstem tumor cells.

PMID- 21075781
TI  - Tamoxifen inhibits malignant peripheral nerve sheath tumor growth in an estrogen
      receptor-independent manner.
AB  - Few therapeutic options are available for malignant peripheral nerve sheath
      tumors (MPNSTs), the most common malignancy associated with neurofibromatosis
      type 1 (NF1). Guided by clinical observations suggesting that some NF1-associated
      nerve sheath tumors are hormonally responsive, we hypothesized that the selective
      estrogen receptor (ER) modulator tamoxifen would inhibit MPNST tumorigenesis in
      vitro and in vivo. To test this hypothesis, we examined tamoxifen effects on
      MPNST cell proliferation and survival, MPNST xenograft growth, and the mechanism
      by which tamoxifen impeded these processes. We found that 1-5 MUM 4-hydroxy
      tamoxifen induced MPNST cell death, whereas 0.01-0.1 MUM 4-hydroxy-tamoxifen
      inhibited mitogenesis. Dermal and plexiform neurofibromas, MPNSTs, and MPNST cell
      lines expressed ERbeta and G-protein-coupled ER-1 (GPER); MPNSTs also expressed
      estrogen biosynthetic enzymes. However, MPNST cells did not secrete 17beta
      estradiol, exogenous 17beta-estradiol did not stimulate mitogenesis or rescue 4
      hydroxy-tamoxifen effects on MPNST cells, and the steroidal antiestrogen ICI
      182,780 did not mimic tamoxifen effects on MPNST cells. Further, ablation of
      ERbeta and GPER had no effect on MPNST proliferation, survival, or tamoxifen
      sensitivity, indicating that tamoxifen acts via an ER-independent mechanism.
      Consistent with this hypothesis, inhibitors of calmodulin (trifluoperazine, W-7),
      another known tamoxifen target, recapitulated 4-hydroxy-tamoxifen effects on
      MPNST cells. Tamoxifen was also effective in vivo, demonstrating potent antitumor
      activity in mice orthotopically xenografted with human MPNST cells. We conclude
      that 4-hydroxy-tamoxifen inhibits MPNST cell proliferation and survival via an ER
      independent mechanism. The in vivo effectiveness of tamoxifen provides a
      rationale for clinical trials in cases of MPNSTs.

PMID- 21075782
TI  - Epigenetic regulation of glial fibrillary acidic protein by DNA methylation in
      human malignant gliomas.
AB  - Glial fibrillary acidic protein (GFAP) is an intermediate filament expressed in
      glial cells that stabilizes and maintains the cytoskeleton of normal astrocytes.
      In glial tumors, GFAP expression is frequently lost with increasing grade of
      malignancy, suggesting that GFAP is important for maintaining glial cell
      morphology or regulating astrocytoma cell growth. Most permanent human glioma
      cell lines are GFAP negative by immunocytochemistry. Given that the GFAP gene is
      not mutated in human glioma specimens or glioma cell lines, we considered
      epigenetic mechanisms, such as promoter methylation, as a cause of silencing of
      GFAP in these tumors. In this study, we treated known GFAP-negative glioma cell
      lines with 5-aza-2'-deoxycytidine to examine GFAP promoter hypermethylation.
      Additionally, we performed bisulfite sequencing on primary glioma samples and
      glioma cell lines and showed an inverse relationship between GFAP promoter
      methylation status and GFAP expression. Using a gene reporter assay with the GFAP
      promoter cloned upstream of a luciferase gene, we showed that methylation of the
      GFAP promoter downregulates the expression of the luciferase gene. Our results
      suggest that epigenetic silencing of the GFAP gene through DNA methylation of its
      promoter region may be one mechanism by which GFAP is downregulated in human
      gliomas and glioma cell lines.

PMID- 21075783
TI  - An automatic method of detecting and tracking fiducial markers for alignment in
      electron tomography.
AB  - We presented an automatic method for detecting and tracking colloidal gold
      fiducial markers for alignment in electron tomography (ET). The second-order
      derivative of direction was used to detect a fiducial marker accurately. The
      detection was optimized to be selective to the size of fiducial markers. A
      preliminary tracking result from the normalized correlation coefficient was
      refined using the detector. A constraint model considering the relationship among
      the fiducial markers on different images was developed for removing outlier. The
      three-dimensional positions of the detected fiducial markers and the projection
      parameters of tilt images were calculated for post process. The accuracy of
      detection and tracking results was evaluated from the residues by the software
      IMOD. Application on transmission electron microscopic images also indicated that
      the presented method could provide a useful approach to automatic alignment in
      ET.

PMID- 21075784
TI  - Collagen-induced expression of collagenase-3 by primary chondrocytes is mediated
      by integrin &alpha;1 and discoidin domain receptor 2: a protein kinase C
      dependent pathway.
AB  - OBJECTIVES: To investigate whether maintaining the chondrocyte's native
      pericellular matrix prevents collagen-induced up-regulation of collagenase-3 (MMP
      13) and whether integrin alpha1 (ITGalpha1) and/or discoidin domain receptor 2
      (DDR2) modulate MMP-13 expression and which signalling pathway plays a role in
      collagen-stimulated MMP-13 expression. METHODS: Goat articular chondrocytes and
      chondrons were cultured on collagen coatings. Small interfering RNA (siRNA)
      oligonucleotides targeted against ITGalpha1 and DDR2 were transfected into
      primary chondrocytes. Chemical inhibitors for mitogen-activated protein kinase
      kinase (MEK1) (PD98059), focal adhesion kinase (FAK) (FAK inhibitor 14), mitogen
      activated protein kinase 8 (JNK) (SP600125) and protein kinase C (PKC) (PKC412),
      and a calcium chelator (BAPTA-AM) were used in cell cultures. Real-time PCR was
      performed to examine gene expression levels of MMP-13, ITGalpha1 and DDR2 and
      collagenolytic activity was determined by measuring the amount of hydroxyproline
      released in the culture medium. RESULTS: Maintaining the chondrocyte's native
      pericellular matrix prevented MMP-13 up-regulation and collagenolytic activity
      when the cells were cultured on a collagen coating. Silencing of ITGalpha1 and
      DDR2 reduced MMP-13 gene expression and collagenolytic activity by primary
      chondrocytes cultured on collagen. Incubation with the PKC inhibitor strongly
      reduced MMP-13 gene expression levels. Gene expression levels of MMP-13 were also
      decreased by chondrocytes incubated with the MEK, FAK or JNK inhibitor.
      CONCLUSION: Maintaining the native pericellular matrix of chondrocytes prevents
      collagen-induced up-regulation of MMP-13. Both ITGalpha1 and DDR2 modulate MMP-13
      expression after direct contact between chondrocytes and collagen. PKC, FAK, MEK
      and JNK are involved in collagen-stimulated expression of MMP-13.

PMID- 21075786
TI  - A high incidental rise in cardiac troponin I carries a higher mortality risk in
      older patients than in those with a diagnosed acute coronary syndrome.

PMID- 21075785
TI  - A prospective assessment of the role of bronchoscopy and bronchoalveolar lavage
      in evaluation of children with pulmonary tuberculosis.
AB  - OBJECTIVE: To assess the diagnostic yield of fibreoptic bronchoscopy and
      bronchoalveolar lavage (BAL) compared to gastric aspiration (GA) in children with
      probable pulmonary tuberculosis (TB). METHODS: Children with probable pulmonary
      TB were subjected to bronchoscopy, BAL and gastric aspiration. The samples were
      examined for acid fast bacilli (AFB) on smear. RESULTS: A total of 52 children
      underwent bronchoscopy with BAL and GA. AFB on smear was identified in 19
      (36.5%); BAL was positive in 16 (30.8%) and GA was positive in 11 (21.15%). GA
      alone was positive in 3 (5.67%) while BAL alone was positive in 8 (15.38%).
      Bronchoscopy detected airways' abnormality in 29 (56%) of patients. One GA and
      BAL detected AFB in majority of patients. CONCLUSION: The diagnostic yield for
      AFB from BAL was better than that from GA in children with probable pulmonary TB.
      Combining one GA and bronchoscopy may improve AFB yield in children with
      pulmonary TB.

PMID- 21075787
TI  - Alas, poor Laennec!

PMID- 21075788
TI  - Hypoglycaemia, phaeochromocytoma and features of acromegaly: a unifying
      diagnosis?

PMID- 21075789
TI  - Challenges in ethics, safety, best practices, and oversight regarding HIT
      vendors, their customers, and patients: a report of an AMIA special task force.
AB  - The current commercial health information technology (HIT) arena encompasses a
      number of competing firms that provide electronic health applications to
      hospitals, clinical practices, and other healthcare-related entities. Such
      applications collect, store, and analyze patient information. Some vendors
      incorporate contract language whereby purchasers of HIT systems, such as
      hospitals and clinics, must indemnify vendors for malpractice or personal injury
      claims, even if those events are not caused or fostered by the purchasers. Some
      vendors require contract clauses that force HIT system purchasers to adopt vendor
      defined policies that prevent the disclosure of errors, bugs, design flaws, and
      other HIT-software-related hazards. To address this issue, the AMIA Board of
      Directors appointed a Task Force to provide an analysis and insights. Task Force
      findings and recommendations include: patient safety should trump all other
      values; corporate concerns about liability and intellectual property ownership
      may be valid but should not over-ride all other considerations; transparency and
      a commitment to patient safety should govern vendor contracts; institutions are
      duty-bound to provide ethics education to purchasers and users, and should commit
      publicly to standards of corporate conduct; and vendors, system purchasers, and
      users should encourage and assist in each others' efforts to adopt best
      practices. Finally, the HIT community should re-examine whether and how
      regulation of electronic health applications could foster improved care, public
      health, and patient safety.

PMID- 21075791
TI  - Effects of school district factors on alcohol consumption: results of a multi
      level analysis among Danish adolescents.
AB  - BACKGROUND: Area-level socio-economic factors are significantly related to a
      population's health. This study investigates how school district-level factors
      affect the initiation of alcohol drinking of Danish adolescents. METHODS: A
      survey sample of 11,223 female and male pupils in the 7th grade from 447 schools
      across Denmark was analysed for the outcome variable drinking initiation and a
      number of individual level predictors. Aggregated variables on school district
      level were created from national registry data for education, occupational level
      and household savings of residents, type of housing and land use characteristics.
      RESULTS: About 40% of all respondents (45.8% males and 35.2% females) had ever
      drunk more than one glass of alcoholic beverage. Mixed-effects logistic
      regression showed that significant individual level predictors for drinking
      initiation were male gender, a lower performance at school, perceived peer group
      drinking and the perceived daily drinking of the father. On school district
      level, adolescents were more likely to initiate alcohol consumption in school
      districts with higher farming land use and less likely in those with higher
      proportion of private apartment buildings. Other school district factors were not
      associated with drinking initiation when controlled for individual level factors.
      CONCLUSIONS: The impact of socio-economic variables at school district level
      seems to be smaller in the welfare state of Denmark than known for other
      countries. However, residence in rural areas may be a direct disadvantage for
      youth, indicating a need for region-specific prevention programmes.

PMID- 21075792
TI  - NCBI Epigenomics: a new public resource for exploring epigenomic data sets.
AB  - The Epigenomics database at the National Center for Biotechnology Information
      (NCBI) is a new resource that has been created to serve as a comprehensive public
      resource for whole-genome epigenetic data sets
      (www.ncbi.nlm.nih.gov/epigenomics). Epigenetics is the study of stable and
      heritable changes in gene expression that occur independently of the primary DNA
      sequence. Epigenetic mechanisms include post-translational modifications of
      histones, DNA methylation, chromatin conformation and non-coding RNAs. It has
      been observed that misregulation of epigenetic processes has been associated with
      human disease. We have constructed the new resource by selecting the subset of
      epigenetics-specific data from general-purpose archives, such as the Gene
      Expression Omnibus, and Sequence Read Archives, and then subjecting them to
      further review, annotation and reorganization. Raw data is processed and mapped
      to genomic coordinates to generate 'tracks' that are a visual representation of
      the data. These data tracks can be viewed using popular genome browsers or
      downloaded for local analysis. The Epigenomics resource also provides the user
      with a unique interface that allows for intuitive browsing and searching of data
      sets based on biological attributes. Currently, there are 69 studies, 337 samples
      and over 1100 data tracks from five well-studied species that are viewable and
      downloadable in Epigenomics.

PMID- 21075793
TI  - Expression of distinct RNAs from 3' untranslated regions.
AB  - The 3' untranslated regions (3'UTRs) of eukaryotic genes regulate mRNA stability,
      localization and translation. Here, we present evidence that large numbers of
      3'UTRs in human, mouse and fly are also expressed separately from the associated
      protein-coding sequences to which they are normally linked, likely by post
      transcriptional cleavage. Analysis of CAGE (capped analysis of gene expression),
      SAGE (serial analysis of gene expression) and cDNA libraries, as well as
      microarray expression profiles, demonstrate that the independent expression of
      3'UTRs is a regulated and conserved genome-wide phenomenon. We characterize the
      expression of several 3'UTR-derived RNAs (uaRNAs) in detail in mouse embryos,
      showing by in situ hybridization that these transcripts are expressed in a cell-
      and subcellular-specific manner. Our results suggest that 3'UTR sequences can
      function not only in cis to regulate protein expression, but also intrinsically
      and independently in trans, likely as noncoding RNAs, a conclusion supported by a
      number of previous genetic studies. Our findings suggest novel functions for
      3'UTRs, as well as caution in the use of 3'UTR sequence probes to analyze gene
      expression.

PMID- 21075794
TI  - Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double
      strand break repair.
AB  - MSH6, a key component of the MSH2-MSH6 complex, plays a fundamental role in the
      repair of mismatched DNA bases. Herein, we report that MSH6 is a novel Ku70
      interacting protein identified by yeast two-hybrid screening. Ku70 and Ku86 are
      two key regulatory subunits of the DNA-dependent protein kinase, which plays an
      essential role in repair of DNA double-strand breaks (DSBs) through the non
      homologous end-joining (NEHJ) pathway. We found that association of Ku70 with
      MSH6 is enhanced in response to treatment with the radiomimetic drug
      neocarzinostatin (NCS) or ionizing radiation (IR), a potent inducer of DSBs.
      Furthermore, MSH6 exhibited diffuse nuclear staining in the majority of untreated
      cells and forms discrete nuclear foci after NCS or IR treatment. MSH6 colocalizes
      with gamma-H2AX at sites of DNA damage after NCS or IR treatment. Cells depleted
      of MSH6 accumulate high levels of persistent DSBs, as detected by formation of
      gamma-H2AX foci and by the comet assay. Moreover, MSH6-deficient cells were also
      shown to exhibit impaired NHEJ, which could be rescued by MSH6 overexpression.
      MSH6-deficient cells were hypersensitive to NCS- or IR-induced cell death, as
      revealed by a clonogenic cell-survival assay. These results suggest a potential
      role for MSH6 in DSB repair through upregulation of NHEJ by association with
      Ku70.

PMID- 21075795
TI  - AgBase: supporting functional modeling in agricultural organisms.
AB  - AgBase (http://www.agbase.msstate.edu/) provides resources to facilitate modeling
      of functional genomics data and structural and functional annotation of
      agriculturally important animal, plant, microbe and parasite genomes. The website
      is redesigned to improve accessibility and ease of use, including improved search
      capabilities. Expanded capabilities include new dedicated pages for horse, cat,
      dog, cotton, rice and soybean. We currently provide 590 240 Gene Ontology (GO)
      annotations to 105 454 gene products in 64 different species, including GO
      annotations linked to transcripts represented on agricultural microarrays. For
      many of these arrays, this provides the only functional annotation available. GO
      annotations are available for download and we provide comprehensive, species
      specific GO annotation files for 18 different organisms. The tools available at
      AgBase have been expanded and several existing tools improved based upon user
      feedback. One of seven new tools available at AgBase, GOModeler, supports
      hypothesis testing from functional genomics data. We host several associated
      databases and provide genome browsers for three agricultural pathogens. Moreover,
      we provide comprehensive training resources (including worked examples and
      tutorials) via links to Educational Resources at the AgBase website.

PMID- 21075796
TI  - Protein inactivation in mycobacteria by controlled proteolysis and its
      application to deplete the beta subunit of RNA polymerase.
AB  - Using a component of the Escherichia coli protein degradation machinery, we have
      established a system to regulate protein stability in mycobacteria. A protein tag
      derived from the E. coli SsrA degradation signal did not affect several reporter
      proteins in wild-type Mycobacterium smegmatis or Mycobacterium tuberculosis.
      Expression of the adaptor protein SspB, which recognizes this modified tag and
      helps deliver tagged proteins to the protease ClpXP, strongly decreased the
      activities and protein levels of different reporters. This inactivation did not
      occur when the function of ClpX was inhibited. Using this system, we constructed
      a conditional M. smegmatis knockdown mutant in which addition of
      anhydrotetracycline (atc) caused depletion of the beta subunit of RNA polymerase,
      RpoB. The impact of atc on this mutant was dose-dependent. Very low amounts of
      atc did not prevent growth but increased sensitivity to an antibiotic that
      inactivates RpoB. Intermediate amounts of RpoB knockdown resulted in
      bacteriostasis and a more substantial depletion led to a decrease in viability by
      up to 99%. These studies identify SspB-mediated proteolysis as an efficient
      approach to conditionally inactivate essential proteins in mycobacteria. They
      further demonstrate that depletion of RpoB by ~ 93% is sufficient to cause death
      of M. smegmatis.

PMID- 21075797
TI  - Update of the FANTOM web resource: from mammalian transcriptional landscape to
      its dynamic regulation.
AB  - The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4)
      research collaboration set out to better understand the transcriptional network
      that regulates macrophage differentiation and to uncover novel components of the
      transcriptome employing a series of high-throughput experiments. The primary and
      unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5'
      ends with a second-generation sequencer to quantify promoter activities even in
      the absence of gene annotation. Additional genome-wide experiments complement the
      setup including short RNA sequencing, microarray gene expression profiling on
      large-scale perturbation experiments and ChIP-chip for epigenetic marks and
      transcription factors. All the experiments are performed in a differentiation
      time course of the THP-1 human leukemic cell line. Furthermore, we performed a
      large-scale mammalian two-hybrid (M2H) assay between transcription factors and
      monitored their expression profile across human and mouse tissues with qRT-PCR to
      address combinatorial effects of regulation by transcription factors. These
      interdependent data have been analyzed individually and in combination with each
      other and are published in related but distinct papers. We provide all data
      together with systematic annotation in an integrated view as resource for the
      scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled
      a rich set of derived analysis results including published predicted and
      validated regulatory interactions. Here we introduce the resource and its update
      after the initial release.

PMID- 21075798
TI  - PhylomeDB v3.0: an expanding repository of genome-wide collections of trees,
      alignments and phylogeny-based orthology and paralogy predictions.
AB  - The growing availability of complete genomic sequences from diverse species has
      brought about the need to scale up phylogenomic analyses, including the
      reconstruction of large collections of phylogenetic trees. Here, we present the
      third version of PhylomeDB (http://phylomeDB.org), a public database for genome
      wide collections of gene phylogenies (phylomes). Currently, PhylomeDB is the
      largest phylogenetic repository and hosts 17 phylomes, comprising 416,093 trees
      and 165,840 alignments. It is also a major source for phylogeny-based orthology
      and paralogy predictions, covering about 5 million proteins in 717 fully
      sequenced genomes. For each protein-coding gene in a seed genome, the database
      provides original and processed alignments, phylogenetic trees derived from
      various methods and phylogeny-based predictions of orthology and paralogy
      relationships. The new version of phylomeDB has been extended with novel data
      access and visualization features, including the possibility of programmatic
      access. Available seed species include model organisms such as human, yeast,
      Escherichia coli or Arabidopsis thaliana, but also alternative model species such
      as the human pathogen Candida albicans, or the pea aphid Acyrtosiphon pisum.
      Finally, PhylomeDB is currently being used by several genome sequencing projects
      that couple the genome annotation process with the reconstruction of the
      corresponding phylome, a strategy that provides relevant evolutionary insights.

PMID- 21075800
TI  - Under-reporting of errors: an information technology perspective.

PMID- 21075801
TI  - An evaluation of telehealth websites for design, literacy, information and
      content.
AB  - We examined 62 telehealth websites using four assessment criteria: design,
      literacy, information and telehealth content. The websites came from the member
      list of the American Telemedicine Association and the Office for the Advancement
      of Telehealth and partner sites, and were included if they were currently active
      and at least three clicks deep. Approximately 130 variables were examined for
      each website by two independent researchers. The websites reviewed contained most
      of the design variables (mean 74%, SD 6), but fewer of those relating to literacy
      (mean 26%, SD 6), website information (mean 35%, SD 16) and telehealth content
      (mean 37%, SD 18). Only 29% of websites encouraged users to ask about telehealth,
      and 19% contained information on overcoming telehealth barriers. Nonetheless, 84%
      promoted awareness of telehealth. All evaluation assessments were significantly
      correlated with each other except for literacy and information. The present study
      identified various matters that should be addressed when developing telehealth
      websites. Although much of this represents simple common sense in website design,
      our evaluation demonstrates that there is still much room for improvement.

PMID- 21075799
TI  - The mRNA cap-binding complex stimulates the formation of pre-initiation complex
      at the promoter via its interaction with Mot1p in vivo.
AB  - The cap-binding complex (CBC) binds to the cap structure of mRNA to protect it
      from exonucleases as well as to regulate downstream post-transcriptional events,
      translational initiation and nonsense-mediated mRNA decay. However, its role in
      regulation of the upstream transcriptional events such as initiation or
      elongation remains unknown. Here, using a formaldehyde-based in vivo cross
      linking and chromatin immunoprecipitation assay in conjunction with
      transcriptional, mutational and co-immunoprecipitational analyses, we show that
      CBC is recruited to the body of yeast gene, and then stimulates the formation of
      pre-initiation complex (PIC) at several yeast promoters through its interaction
      with Mot1p (modifier of transcription). Mot1p is recruited to these promoters,
      and enhances the PIC formation. We find that CBC promotes the recruitment of
      Mot1p which subsequently stimulates PIC formation at these promoters.
      Furthermore, the formation of PIC is essential for recruitment of CBC. Thus, our
      study presents an interesting observation that an mRNA binding factor exhibits a
      reciprocal synergistic effect on formation of PIC (and hence transcriptional
      initiation) at the promoter, revealing a new pathway of eukaryotic gene
      regulation in vivo.

PMID- 21075802
TI  - Patients' experiences of telerehabilitation at home after shoulder joint
      replacement.
AB  - We investigated the experience of ten patients who received video-based
      physiotherapy at home for two months after a shoulder joint replacement.
      Videoconferencing took place via the patient's home broadband connection at a
      bandwidth of 256-768 kbit/s. Qualitative interviews were carried out, transcribed
      and analysed. Through qualitative content analysis six categories were
      identified: (1) a different reinforced communication; (2) pain-free exercising as
      an effective routine; (3) from a dependent patient to a strengthened person at
      home; (4) closeness at a distance; (5) facilitated daily living; and (6)
      continuous physiotherapy chain. The access to bodily knowledge, continuity,
      collaboration and being at home were all aspects that contributed to the
      patients' recovery. The patients described experiences of safety, and
      strengthening during their daily exercise routine at home. The frequent interplay
      with the patient during telerehabilitation made it possible for the
      physiotherapist to make an individual judgement about each patient; this could be
      one reason for the positive findings. Home video-based physiotherapy may be
      useful in other kinds of physiotherapy.

PMID- 21075803
TI  - On model selection and model misspecification in causal inference.
AB  - Standard variable selection procedures, primarily developed for the construction
      of outcome prediction models, are routinely applied when assessing exposure
      effects in observational studies. We argue that this tradition is sub-optimal and
      prone to yield bias in exposure effect estimators as well as their corresponding
      uncertainty estimators. We weigh the pros and cons of confounder-selection
      procedures and propose a procedure directly targeting the quality of the exposure
      effect estimator. We further demonstrate that certain strategies for inferring
      causal effects have the desirable features (a) of producing (approximately) valid
      confidence intervals, even when the confounder-selection process is ignored, and
      (b) of being robust against certain forms of misspecification of the association
      of confounders with both exposure and outcome.

PMID- 21075804
TI  - H-FABP in cases of carbon monoxide intoxication admitted to the emergency room.
AB  - INTRODUCTION: Carbon monoxide (CO) intoxication causes cardiovascular problems as
      a result of diffuse tissue hypoxia. Cardiac biochemical markers and
      electrocardiographic changes have been reported in CO intoxications. Human fatty
      acid-binding protein (H-FABP) has been recently used as a reliable marker in
      identifying early cardiac damage. In this prospective study, we aimed to
      investigate the advantages of the use of H-FABP, in evaluating the findings of
      myocardial ischemia in patients with CO intoxication in our region. METHODS:
      Twenty four successive patients admitted to the emergency department with acute
      CO intoxication were included in our study. Serum traditional markers and H-FABP
      were also taken in the earliest period for evaluation of cardiac damage. RESULTS:
      The creatinine kinase MB (CKMB) levels were positive in 11 of the patients;
      however, H-FABP and troponin T levels were positive in only 3 of them. One of
      these subjects had elevated level of H-FABP in the short-term and increasing
      troponin T level increasing level of troponin T during the follow-up period.
      CONCLUSION: The obtained data supports the use of H-FABP, a specific indicator in
      identifying the cardiotoxicity of CO intoxications at an early phase.

PMID- 21075805
TI  - Gender-related difference in liver injury induced by Dioscorea bulbifera L.
      rhizome in mice.
AB  - The present study was undertaken to investigate the gender-related liver injury
      induced by Dioscorea bulbifera L. (DB), a traditional medicinal plant, in mice,
      and further explored its hepatotoxic chemical compound. Serum and liver tissue
      samples were collected at 0, 4, 8, 12 h, after mice were administrated orally
      with 640 mg/kg ethyl acetate extracts (EF) isolated from DB. After treatments,
      serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were
      both significantly elevated. Liver lipid peroxidation (LPO) level increased,
      while glutathione amounts, glutathione-S-transferase (GST), superoxide dismutase
      (SOD) and catalase (CAT) activities all decreased in the time-dependent manner.
      Further analysis demonstrated that ALT and AST activities in female mice were
      significantly lower than those in male. Meanwhile, liver glutathione amounts and
      CAT activity in female mice after giving EF for 12 h were both higher than those
      in male. Further, comparing the liver injury induced by Diosbulbin B isolated
      from DB with that induced by EF on the basis of chemical analysis for the amounts
      of Diosbulbin B in EF of DB, we found that Diosbulbin B could be the main
      hepatotoxic chemical compound in DB. Taken together, our results show that DB can
      induce gender-related liver oxidative stress injury in mice, and its main
      hepatotoxic chemical compound is Diosbulbin B, for the first time.

PMID- 21075806
TI  - The effect of high-fat diet-induced obesity on cardiovascular toxicity in Wistar
      albino rats.
AB  - The consumption of a high-fat diet (HFD) is considered a risk factor for obesity
      development. Nonetheless, a causal role of dietary fat has never been documented,
      because of inadequate animal models. In our study, one group of rats was fed with
      standard rat diet, while other group of rats fed with high-fat diet for 4 weeks.
      After 4 weeks of feeding, the hemodynamic parameters in the rats fed with HFD
      were significantly increased as compared with control rats. Rats fed with HFD had
      elevated levels of serum lipids, insulin, leptin, glucose and apolipoprotein B.
      Lipid peroxides and caspase-3 levels were increased while serum apolipoprotein A1
      and antioxidant enzymes levels in heart tissues were decreased in HFD-induced
      obesity in rats as compared to normal healthy control rats fed on standard rat
      pellet diet. This model of diet-induced obesity will be a useful tool for
      studying the mechanisms by which dietary fat induces the obesity in humans.

PMID- 21075807
TI  - Novel platinum-N-heterocyclic carbene complex is more cardiotoxic than cis-platin
      in rats.
AB  - Cis-platin and other platinum complexes are important chemotherapeutic agents
      useful in the treatment of several cancers. However, therapeutic usage of cis
      platin and other platinum complex are limited by their undesirable side effects
      including cardiotoxicity. In this context, we aimed to compare the damage caused
      in heart by cis-platin and novel platinum-N-heterocyclic carbene (Pt-NHC)
      complex. For this purpose, 35 Sprague-Dawley rats were divided randomly into five
      equal groups (n = 7 for each group). Cis-platin and novel Pt-NHC complex were
      intraperitoneally administered at a single dose of 5 mg/kg and 10 mg/kg and then
      sacrificed 10 days after this treatment. The heart tissues were taken from all
      rats for determination of oxidative and myocardial damage. Cis-platin and novel
      Pt-NHC complex caused oxidative and histological damage in the heart tissue in a
      dose-dependent manner (p < 0.05). On the other hand, at the same dose levels, cis
      platin caused lower oxidative and histological damage in heart tissue compared to
      novel Pt-NHC complex. These results suggest that novel Pt-NHC complex is more
      cardiotoxic than cis-platin.

PMID- 21075808
TI  - Is maternal smoking during pregnancy a risk factor for hyperkinetic disorder?-
      Findings from a sibling design.
AB  - BACKGROUND: Studies have consistently shown that pregnancy smoking is associated
      with twice the risk of hyperactivity/inattention problems in the offspring. An
      association of this magnitude may indicate behavioural difficulties as one of the
      most important health effects related to smoking during pregnancy. However,
      social and genetic confounders may fully or partially account for these findings.
      METHODS: A cohort including all singletons born in Finland from 1 January 1987
      through 31 December 2001 was followed until 1 January 2006 based on linkage of
      national registers. Data were available for 97% (N = 868,449) of the population.
      We followed singleton children of smoking and non-smoking mothers until they had
      an International Classification of Diseases, 10th revision, diagnosis of
      hyperkinetic disorder (HKD) or to the end of the observation period. We used
      sibling-matched Cox regression analyses to control for social and genetic
      confounding. RESULTS: We found a much smaller association between exposure to
      maternal smoking during pregnancy and risk of HKD in children using the sibling
      matched analysis [hazards ratio (HR) = 1.20, 95% confidence interval (CI) 0.97
      1.49] than was observed in the entire cohort (HR 2.01, 95% CI 1.90-2.12).
      CONCLUSIONS: Our findings suggest that the strong association found in previous
      studies may be due to time-stable familial factors, such as environmental and
      genetic factors. If smoking is a causal factor, the effect is small and less
      important than what the previous studies indicate.

PMID- 21075809
TI  - Cancer screening: inequalities ... in the data.

PMID- 21075810
TI  - Watching football matches and the risk of acute myocardial infarction.

PMID- 21075811
TI  - Surgery for degenerative mitral valve disease.

PMID- 21075813
TI  - Family planning loses out to HIV and AIDS in development aid, shows analysis.

PMID- 21075816
TI  - Hospital pays out six figure sum to widow for error over antifungal drug.

PMID- 21075818
TI  - Management of venous ulcer disease.

PMID- 21075820
TI  - EU drug monitoring agency voices concerns over "legal highs".

PMID- 21075821
TI  - Mortality rate comparison after switching from continuous to prolonged
      intermittent renal replacement for acute kidney injury in three intensive care
      units from different countries.
AB  - BACKGROUND: Prolonged intermittent renal replacement therapy (PIRRT) is a
      dialysis modality for critically ill patients that in theory combines the
      superior detoxification and haemodynamic stability of the continuous renal
      replacement therapy (CRRT) with the operational convenience, reduced haemorrhagic
      risk and low cost of conventional intermittent haemodialysis. However, the extent
      to which PIRRT should replace these other modalities is uncertain because
      comparative studies of mortality are lacking. We retrospectively examined the
      mortality data from three general intensive care units (ICUs) in different
      countries that have switched their predominant therapeutic approach from CRRT to
      PIRRT. We assessed whether this practice change was associated with a change in
      mortality rate. METHODS: Data were analysed from ICUs in New Zealand, Australia
      and Italy. The study population comprised all patients requiring renal
      replacement therapy from 1 January 1995 to 31 December 2005 (n = 1347), the
      period of time spanning the change from CRRT to PIRRT in each unit. Poisson
      regression models were used to estimate the incident rate ratio (IRR) for death,
      comparing the periods before and after change to PIRRT in each unit. Estimates
      were adjusted for patient illness severity (APACHE II score) and for the
      underlying time trend in mortality rate over time. RESULTS: The change from CRRT
      to PIRRT was not associated with any increase in mortality rate, with an adjusted
      IRR of 1.02 (0.61-1.71). The IRR was virtually identical in the three ICUs (P
      value = 0.63 for the difference in the IRR between ICUs). CONCLUSIONS: Switching
      from CRRT to PIRRT was not associated with a change in mortality rate. Pending
      the results of a randomized trial, our study provides evidence that PIRRT might
      be equivalent to CRRT in the general ICU patient.

PMID- 21075822
TI  - Epidermal growth factor induces a sexually dimorphic proliferative response of
      lactotroph cells through protein kinase C-ERK1/2-Pit-1 in vitro.
AB  - Lactotroph cells display morphological and functional heterogeneity, a feature
      which is closely related to the oestrogenic environment. In this study, we
      focused on sex-related differences linked to the proliferative and secretory
      responses of lactotrophs exposed to EGF in vitro. Furthermore, we addressed the
      involvement of the PKCepsilon/ERK1/2 signalling pathway and the contribution of
      Pit-1 in the EGF actions in primary pituitary cultures from male and female rats.
      EGF promoted a differential proliferative activity on PRL cells, which was
      closely associated to the sex, as revealed by the uptake of bromodeoxyuridine
      (BrdU). In females, the mitogenic activity was up to nine times greater, whereas
      in males, the number of BrdU-labelled PRL cells was only doubled compared to
      control. However, in both models, EGF had a similar effectiveness in promoting
      PRL secretion. EGF also induced a significant increase in the PKCepsilon, P -ERK
      1/2, and Pit-1 protein levels, which were higher in females than in males. Pre
      incubation with BIM blocked EGF-induced ERK 1/2 activation and Pit-1 expression.
      These results suggest a sexually dimorphic response of lactotroph cells to the
      proliferative effects of EGF, with the PKCepsilon/ERK1/2 Pit-1 pathway being
      involved in this action.

PMID- 21075823
TI  - Successful ultrasound-guided foam sclerotherapy for vulval and leg varicosities
      secondary to ovarian vein reflux: a case study.
AB  - Pelvic varicose veins secondary to ovarian vein reflux are common and can present
      with clinical pelvic congestion syndrome (PCS). After assessment with duplex
      ultrasound and venography, treatment often involves surgical ovarian vein
      ligation and more recently embolization of the ovarian vein(s) followed by
      ultrasound-guided foam sclerotherapy (UGFS) of the pelvic tributaries. This paper
      presents one out of many PCS patients treated with UGFS of the pelvic tributaries
      alone, with clinically symptomatic improvement.

PMID- 21075824
TI  - A novel fusion toxin derived from an EpCAM-specific designed ankyrin repeat
      protein has potent antitumor activity.
AB  - PURPOSE: Designed ankyrin repeat proteins (DARPins) hold great promise as a new
      class of binding molecules to overcome the limitations of antibodies for
      biomedical applications. Here, we assessed the potential of an epithelial cell
      adhesion molecule (EpCAM)-specific DARPin (Ec4) for tumor targeting as a fusion
      toxin with Pseudomonas aeruginosa exotoxin A. EXPERIMENTAL DESIGN: DARPin Ec4 was
      genetically fused to a truncated form of Pseudomonas aeruginosa exotoxin A (ETA")
      and expressed in Escherichia coli. The cytotoxicity of Ec4-ETA" was measured
      against tumor cell lines of various histotypes in vitro. Tumor localization and
      antitumor activity were determined in mice bearing 2 different EpCAM-positive
      tumor xenografts. RESULTS: Ec4-ETA" expressed very well in soluble form in the
      cytoplasm of E. coli and yielded up to 40 mg after purification per liter of
      culture. The protein was monomeric and the disulfides of ETA" formed
      spontaneously. Ec4-ETA" bound to EpCAM with low nanomolar affinity, similar to
      free Ec4. Furthermore, it was highly cytotoxic against various EpCAM-positive
      tumor cell lines in vitro with IC(50) values less than 0.005 pmol/L. This effect
      was competed by free Ec4, but not by unspecific DARPins. Upon systemic
      administration in athymic mice, Ec4-ETA" efficiently localized to EpCAM-positive
      tumors to achieve maximum accumulation 48 to 72 hours after injection, whereas an
      irrelevant control fusion toxin did not accumulate. Tumor targeting with Ec4-ETA"
      resulted in a strong antitumor response including complete regressions in some
      animals. CONCLUSIONS: Our data show for the first time the potential of DARPins
      for the generation of protein therapeutics for tumor targeting, and that Ec4-ETA"
      deserves attention for clinical development.

PMID- 21075825
TI  - Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition
      catalyst in burn and smoke inhalation injury.
AB  - During acute lung injury, nitric oxide (NO) exerts cytotoxic effects by reacting
      with superoxide radicals, yielding the reactive nitrogen species peroxynitrite
      (ONOO(-)). ONOO(-) exerts cytotoxic effects, among others, by
      nitrating/nitrosating proteins and lipids, by activating the nuclear repair
      enzyme poly(ADP-ribose) polymerase and inducing VEGF. Here we tested the effect
      of the ONOO(-) decomposition catalyst INO-4885 on the development of lung injury
      in chronically instrumented sheep with combined burn and smoke inhalation injury.
      The animals were randomized to a sham-injured group (n = 7), an injured control
      group [48 breaths of cotton smoke, 3rd-degree burn of 40% total body surface area
      (n = 7)], or an injured group treated with INO-4885 (n = 6). All sheep were
      mechanically ventilated and fluid-resuscitated according to the Parkland formula.
      The injury-related increases in the abundance of 3-nitrotyrosine, a marker of
      protein nitration by ONOO(-), were prevented by INO-4885, providing evidence for
      the neutralization of ONOO(-) action by the compound. Burn and smoke injury
      induced a significant drop in arterial Po(2)-to-inspired O(2) fraction ratio and
      significant increases in pulmonary shunt fraction, lung lymph flow, lung wet-to
      dry weight ratio, and ventilatory pressures; all these changes were significantly
      attenuated by INO-4885 treatment. In addition, the increases in IL-8, VEGF, and
      poly(ADP-ribose) in lung tissue were significantly attenuated by the ONOO(-)
      decomposition catalyst. In conclusion, the current study suggests that ONOO(-)
      plays a crucial role in the pathogenesis of pulmonary microvascular
      hyperpermeability and pulmonary dysfunction following burn and smoke inhalation
      injury in sheep. Administration of an ONOO(-) decomposition catalyst may
      represent a potential treatment option for this injury.

PMID- 21075827
TI  - Using amphibians in laboratory studies: precautions against the emerging
      infectious disease chytridiomycosis.
AB  - The African clawed frog Xenopus laevis is by far the most widely used amphibian
      species in laboratories. In the wild, X. laevis is an asymptomatic carrier of an
      emerging infectious disease called chytridiomycosis. The vector is the chytrid
      fungus Batrachochytrium dendrobatidis (Bd), which has devastating effects on wild
      amphibian populations around the world. The impact of Bd on the metabolism of X.
      laevis has not been comprehended yet. However, even if asymptomatic, an infection
      is likely to affect the individual's physiology, immunology, development,
      reproduction and overall response to stress from a purely medical point of view,
      which will introduce noise and therefore increase variance within experimental
      groups of X. laevis. This could have implications on the scientific results from
      studies using this species. Here, we review the current knowledge on treatments
      of infected amphibians and propose a hygiene protocol adapted to laboratory
      populations and amphibian husbandry. Following the presented sanitation
      guidelines could further prevent the spread of Bd and probably of other amphibian
      pathogens. The sanitation guidelines will help to reduce the impact of amphibian
      husbandry on natural populations and must be considered a crucial contribution to
      amphibian conservation, as today 32% of all amphibians are considered threatened.

PMID- 21075826
TI  - Titin-based mechanosensing and signaling: role in diaphragm atrophy during
      unloading?
AB  - The diaphragm, the main muscle of inspiration, is constantly subjected to
      mechanical loading. One of the very few occasions during which diaphragm loading
      is arrested is during controlled mechanical ventilation in the intensive care
      unit. Recent animal studies indicate that the diaphragm is extremely sensitive to
      unloading, causing rapid muscle fiber atrophy: unloading-induced diaphragm
      atrophy and the concomitant diaphragm weakness has been suggested to contribute
      to the difficulties in weaning patients from ventilatory support. Little is known
      about the molecular triggers that initiate the rapid unloading atrophy of the
      diaphragm, although proteolytic pathways and oxidative signaling have been shown
      to be involved. Mechanical stress is known to play an important role in the
      maintenance of muscle mass. Within the muscle's sarcomere titin is considered to
      play an important role in the stress-response machinery. Titin is the largest
      protein known to date and acts as a mechanosensor that regulates muscle protein
      expression in a sarcomere strain-dependent fashion. Thus, titin is an attractive
      candidate for sensing the sudden mechanical arrest of the diaphragm when patients
      are mechanically ventilated, leading to changes in muscle protein expression.
      Here, we provide a novel perspective on how titin, and its biomechanical sensing
      and signaling, might be involved in the development of mechanical unloading
      induced diaphragm weakness.

PMID- 21075829
TI  - Successful in vitro culture of pre-antral follicles derived from vitrified murine
      ovarian tissue: oocyte maturation, fertilization, and live births.
AB  - Cryopreservation of ovarian tissue is an important option for preserving the
      fertility of cancer patients undergoing chemotherapy and radiotherapy. In this
      study, we examined the viability and function of oocytes derived in vitro from
      pre-antral follicles as an alternative method for restoring fertility. Pre-antral
      follicles (specified as secondary follicle with a diameter around 100-130 MUm)
      were mechanically isolated from vitrified-warmed and fresh adult mouse ovarian
      tissues and cultured for 12 days followed by an ovulation induction protocol at
      the end of this period to initiate oocyte maturation. Oocytes were then released
      from these follicles, fertilized in vitro, and cultured to the blastocyst stage
      and vitrified. After storage in liquid nitrogen for 2 weeks, groups of vitrified
      blastocysts were warmed and transferred into pseudo-pregnant recipient females.
      Although most of the isolated mouse pre-antral follicles from fresh (79.4%) and
      vitrified (75.0%) ovarian tissues survived the 12-day in vitro culture period,
      significantly fewer mature oocytes developed from vitrified-warmed pre-antral
      follicles than from the fresh controls (62.2 vs 86.4%, P<0.05). No difference was
      observed in embryo cleavage rates between these two groups, but the proportion of
      embryos that developed into blastocysts in the vitrification group was only half
      that of the controls (24.2 vs 47.2%, P<0.05). Nevertheless, live births of
      healthy normal pups were achieved after transfer of vitrified blastocysts derived
      from both experimental groups. This study shows that successful production of
      healthy offspring using an in vitro follicle culture system is feasible, and
      suggests that this procedure could be used in cancer patients who wish to
      preserve their fertility using ovarian tissue cryopreservation.

PMID- 21075830
TI  - Removal of aprotinin from low-dose aprotinin/tranexamic acid antifibrinolytic
      therapy increases transfusion requirements in cardiothoracic surgery.
AB  - This retrospective study investigated whether withdrawal of aprotinin from
      combined low-dose aprotinin/tranexamic acid (TXA) antifibrinolytic therapy
      altered postoperative blood loss and transfusion requirements in patients
      undergoing cardiothoracic surgery employing cardiopulmonary bypass (CPB). The
      study included data from patients receiving a combination of low-dose aprotinin
      (2*10(6) KIU in CPB prime; n=615) and 2000 mg TXA or patients receiving TXA only
      (n=587). In both groups, TXA was given after protamine administration. Study
      endpoints were blood loss, transfusion requirements and reoperation. There were
      no differences in EuroSCORE, CPB time, antiangial medication and baseline
      coagulation parameters between groups. There were more males in the TXA group
      (85%) as compared to the TXA+aprotinin group (77%; P=0.02). Postoperative blood
      loss (0.80+/-0.69 vs. 0.66+/-0.52 l; P=0.001) and transfusion of fresh frozen
      plasma (0.6+/-0.7 vs. 0.4+/-0.6 U; P<0.001), packed cells (3.9+/-5.5 vs. 2.7+/
      3.3 U; P<0.001) and platelets (0.7+/-0.6 vs. 0.5+/-0.6 U; P<0.001) was higher in
      the TXA group than in patients receiving combined therapy, respectively. There
      were more reoperations for bleeding in the TXA group (53 vs. 34, respectively;
      P=0.03) with similar mortality and deterioration in glomerular filtration rate.
      In conclusion, withdrawal of aprotinin from combined antifibrinolytic therapy is
      associated with increased blood loss, transfusion requirements and reoperations.

PMID- 21075831
TI  - Contralateral recurrence of a malignant solitary fibrous tumor of the pleura.
AB  - We present an unusual case of a contralateral recurrence of malignant solitary
      fibrous tumor of the pleura (SFTP) nine years after a complete resection.
      Recurrence of malignant SFTP has already been described, but is usually
      localized. In our case the patient underwent surgical resection for a malignant
      SFTP of the left upper lobe in 2000. Nine years later computed tomography (CT)
      scans showed lesions that were suspicious of tumor recurrence in the right lung.
      Thoracoscopy, wedge-resections and pathological findings revealed four nodules of
      a malignant SFTP of the right middle and lower lobe, histopathologically
      identical to the tumor, which had been resected nine years ago. A coincidental
      mucinous bronchioloalveolar carcinoma of the left lower lobe was resected by
      thoracotomy. To our knowledge this is the first report of contralateral
      recurrence of a malignant SFTP years after complete resection in the literature.
      The possibility of a new primary tumor on the right with local metastasis could
      not be excluded in the clinical and histopathological examinations. Therefore,
      contralateral recurrence of malignant SFTP should be considered in the
      postoperative follow-up even years after complete resection.

PMID- 21075828
TI  - Regulation of proteinases during mouse peri-implantation development: urokinase
      type plasminogen activator expression and cross talk with matrix
      metalloproteinase 9.
AB  - Trophoblast cells express urokinase-type plasminogen activator (PLAU) and may
      depend on its activity for endometrial invasion and tissue remodeling during peri
      implantation development. However, the developmental regulation, tissue
      distribution, and function of PLAU are not completely understood. In this study,
      the expression of PLAU and its regulation by extracellular matrix proteins was
      examined by RT-PCR, immunocytochemistry, and plasminogen-casein zymography in
      cultured mouse embryos. There was a progressive increase in Plau mRNA expression
      in blastocysts cultured on gestation days 4-8. Tissue-type plasminogen activator
      (55 kDa) and PLAU (a triplet of 40, 37, and 31 kDa) were present in conditioned
      medium and embryo lysates, and were adsorbed to the culture plate surface. The
      temporal expression pattern of PLAU, according to semi-quantitative gel
      zymography, was similar in non-adhering embryos and embryos cultured on
      fibronectin, laminin, or type IV collagen, although type IV collagen and laminin
      upregulated Plau mRNA expression. Immunofluorescence revealed PLAU on the surface
      of the mural trophectoderm and in non-spreading giant trophoblast cells.
      Exogenous human plasminogen was transformed to plasmin by cultured embryos and
      activated endogenous matrix metalloproteinase 9 (MMP9). Indeed, the developmental
      expression profile of MMP9 was similar to that of PLAU. Our data suggest that the
      intrinsic developmental program predominantly regulates PLAU expression during
      implantation, and that PLAU could be responsible for activation of MMP9, leading
      to localized matrix proteolysis as trophoblast invasion commences.

PMID- 21075832
TI  - Giant mediastinal teratoma presenting with paroxysmal atrial fibrillation.
AB  - Mediastinum is a common site where benign tumors, like teratomas, can develop.
      Usually, these lesions do not cause any symptoms and the diagnosis is reached
      accidentally. As they enlarge they may cause symptoms by compressing the nearby
      structures of the thorax, mostly the trachea and the bronchi. Extrinsic
      compression of the heart or the great vessels appears to be a very rare
      occurrence. Atrial fibrillation as the first clinical presentation of left atrial
      compression by a giant mediastinal teratoma is extremely uncommon and very few
      cases have been described in the English literature.

PMID- 21075833
TI  - Cigarette smoking and other lifestyle factors in relation to the risk of
      pancreatic cancer death: a prospective cohort study in Japan.
AB  - OBJECTIVE: To examine the association of smoking and lifestyle factors with
      pancreatic cancer death in the prospective design. METHODS: Mortality from
      pancreatic cancer in regard to smoking, body mass index, physical activity, and
      alcohol, coffee and green tea intake, was studied in a prospective cohort of
      30,826 inhabitants in Takayama, Japan. In 1992, each subject completed a self
      administered questionnaire on demographic information, smoking, drinking habits,
      diet, exercise and medical histories. The response rate was 85.3%. RESULTS: From
      1992 to 1999, 33 men and 19 women died due to pancreatic cancer. Hazard ratios
      and 95% confidence intervals were determined using Cox proportional hazards
      models. Women who were defined as current smokers at baseline had significant and
      increased risk of pancreatic cancer death after adjustment for age, body mass
      index and history of diabetes mellitus (Hazard ratio: 4.77, 95% confidence
      intervals: 1.58-14.4). There were significant positive associations of pancreatic
      cancer death with the years of smoking and the number of cigarettes consumed
      daily in women in a dose-dependent manner. Current smokers indicated a non
      significant risk increase in men (Hazard ratio: 3.81, 95% confidence intervals:
      0.88-16.6). Body mass index, physical activity, and alcohol, coffee and green tea
      intake were not significantly associated with pancreatic cancer death.
      CONCLUSIONS: These data suggested that smoking increases the risk of death from
      pancreatic cancer in Japanese women.

PMID- 21075835
TI  - Glycogen-branching enzyme deficiency leads to abnormal cardiac development: novel
      insights into glycogen storage disease IV.
AB  - Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease
      caused by a deficiency in glycogen-branching enzyme (GBE1) activity that results
      in the accumulation of amylopectin-like polysaccharide, which presumably leads to
      osmotic swelling and cell death. This disease is extremely heterogeneous in terms
      of tissue involvement, age of onset and clinical manifestation. The most severe
      fetal form presents as hydrops fetalis; however, its pathogenetic mechanisms are
      largely unknown. In this study, mice carrying a stop codon mutation (E609X) in
      the Gbe1 gene were generated using a gene-driven mutagenesis approach. Homozygous
      mutants (Gbe(-/-) mice) recapitulated the clinical features of hydrops fetalis
      and the embryonic lethality of the severe fetal form of GSD-IV. However, contrary
      to conventional expectations, little amylopectin accumulation and no cell
      degeneration were found in Gbe(-/-) embryonic tissues. Glycogen accumulation was
      reduced in developing hearts of Gbe(-/-)embryos, and abnormal cardiac
      development, including hypertrabeculation and noncompaction of the ventricular
      wall, was observed. Further, Gbe1 ablation led to poor ventricular function in
      late gestation and ultimately caused heart failure, fetal hydrops and embryonic
      lethality. We also found that the cell-cycle regulators cyclin D1 and c-Myc were
      highly expressed in cardiomyocytes and likely contributed to cardiomyocyte
      proliferation and trabeculation/compaction of the ventricular wall. Our results
      reveal that early molecular events associated with Gbe1 deficiency contribute to
      abnormal cardiac development and fetal hydrops in the fetal form of GSD-IV.

PMID- 21075834
TI  - Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour
      suppressor gene, functions in aerobic metabolism and regulates reactive oxygen
      species.
AB  - Common chromosomal fragile sites FRA3B and FRA16D are frequent sites of DNA
      instability in cancer, but their contribution to cancer cell biology is not yet
      understood. Genes that span these sites (FHIT and WWOX, respectively) are often
      perturbed (either increased or decreased) in cancer cells and both are able to
      suppress tumour growth. While WWOX has some tumour suppressor characteristics,
      its normal role and functional contribution to cancer has not been fully
      determined. We find that a significant proportion of Drosophila Wwox interactors
      identified by proteomics and microarray analyses have roles in aerobic
      metabolism. Functional relationships between Wwox and either CG6439/isocitrate
      dehydrogenase (Idh) or Cu-Zn superoxide dismutase (Sod) were confirmed by genetic
      interactions. In addition, altered levels of Wwox resulted in altered levels of
      endogenous reactive oxygen species. Wwox (like FHIT) contributes to pathways
      involving aerobic metabolism and oxidative stress, providing an explanation for
      the 'non-classical tumour suppressor' behaviour of WWOX. Fragile sites, and the
      genes that span them, are therefore part of a protective response mechanism to
      oxidative stress and likely contributors to the differences seen in aerobic
      glycolysis (Warburg effect) in cancer cells.

PMID- 21075836
TI  - Dynamic visual information facilitates object recognition from novel viewpoints.
AB  - Normally, people have difficulties recognizing objects from novel as compared to
      learned views, resulting in increased reaction times and errors. Recent studies
      showed, however, that this "view-dependency" can be reduced or even completely
      eliminated when novel views result from observer's movements instead of object
      movements. This observer movement benefit was previously attributed to extra
      retinal (physical motion) cues. In two experiments, we demonstrate that dynamic
      visual information (that would normally accompany observer's movements) can
      provide a similar benefit and thus a potential alternative explanation.
      Participants performed sequential matching tasks for Shepard-Metzler-like objects
      presented via head-mounted display. As predicted by the literature, object
      recognition performance improved when view changes (45 degrees  or 90 degrees )
      resulted from active observer movements around the object instead of object
      movements. Unexpectedly, however, merely providing dynamic visual information
      depicting the viewpoint change showed an equal benefit, despite the lack of any
      extra-retinal/physical self-motion cues. Moreover, visually simulated rotations
      of the table and hidden target object (table movement condition) yielded similar
      performance benefits as simulated viewpoint changes (scene movement condition).
      These findings challenge the prevailing notion that extra-retinal (physical
      motion) cues are required for facilitating object recognition from novel
      viewpoints, and highlight the importance of dynamic visual cues, which have
      previously received little attention.

PMID- 21075837
TI  - The change of spherical aberration during accommodation and its effect on the
      accommodation response.
AB  - Theoretical and ray-tracing calculations on an accommodative eye model based on
      published anatomical data, together with wave-front experimental results on 15
      eyes, are computed to study the change of spherical aberration during
      accommodation and its influence on the accommodation response. The three
      methodologies show that primary spherical aberration should decrease during
      accommodation, while secondary spherical aberration should increase. The
      hyperbolic shape of the lens' surfaces is the main factor responsible for the
      change of those aberrations during accommodation. Assuming that the eye
      accommodated to optimize image quality by minimizing the RMS of the wave front,
      it is shown that primary spherical aberration decreases the accommodation
      response, while secondary spherical aberration slightly increases it. The total
      effect of the spherical aberration is a reduction of around 1/7 D per diopter of
      stimulus approximation, although that value depends on the pupil size and its
      reduction during accommodation. The apparent accommodation error (lead and lag),
      typically present in the accommodation/response curve, could then be explained as
      a consequence of the strategy used by the visual system, and the apparatus of
      measurement, to select the best image plane that can be affected by the change of
      the spherical aberration during accommodation.

PMID- 21075838
TI  - Endothelin ETB receptor is involved in sex differences in the development of
      balloon injury-induced neointimal formation.
AB  - The purpose of this study was to evaluate the involvement of endothelin (ET)(B)
      receptor-mediated action in the sex differences in balloon injury-induced
      neointimal formation using the spotting-lethal rat, which carries a naturally
      occurring deletion in its ET(B) receptor gene. Male and female ET(B)-deficient
      and wild-type rats underwent balloon injury of the carotid artery. In the wild
      type rats, the neointima/media ratio was significantly lower in females than in
      males, but this sex difference was attenuated by ovariectomy and restored by
      treatment with 17beta-estradiol (20 MUg/kg/day). In the ET(B)-deficient rats, the
      neointima/media ratio of the male and female rats was markedly increased to the
      same level, and this increase was not affected by ovariectomy or 17beta-estradiol
      treatment. Treatment with (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4
      methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine-6
      carboxylic acid (J-104132) (10 mg/kg/day), an ET(A)/ET(B) dual receptor
      antagonist, markedly decreased the neointima/media ratio of the male wild-type
      rats and the male and female ET(B)-deficient rats, but not the female wild-type
      rats. In addition, 2R-(4-propoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N-(2,6
      diethylphenyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (A-192621) (30
      mg/kg/day), a selective ET(B) receptor antagonist, abolished the sex difference
      of balloon injury-induced neointimal formation. 2R-(4-methoxyphenyl)-4S-(1,3
      benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R
      carboxylic acid (ABT-627) (10 mg/kg/day), a selective ET(A) receptor antagonist,
      and J-104132 (10 mg/kg/day) markedly decreased the neointima/media ratio to the
      same extent in males but not intact females. These results indicate that the sex
      difference in balloon injury-induced neointimal formation was abolished by
      genetic ET(B) receptor deficiency or its pharmacological blockade. The lack of a
      vasoprotective effect of estrogen and the augmentation of ET(A) receptor-mediated
      action seem to be responsible for the abolition of sex differences in the ET(B)
      receptor-inhibited condition.

PMID- 21075839
TI  - Modulation of the glucagon-like peptide-1 receptor signaling by naturally
      occurring and synthetic flavonoids.
AB  - The glucagon-like peptide 1 receptor (GLP-1R) is a promising target for the
      treatment of type II diabetes mellitus because of its role in metabolic
      homeostasis. In recent years, difficulties with peptide therapies have driven the
      search for small-molecule compounds to modulate the activity of this receptor. We
      recently identified quercetin, a naturally occurring flavonoid, as a probe
      dependent, pathway-selective allosteric modulator of GLP-1R-mediated signaling.
      Using Chinese hamster ovary cells expressing the human GLP-1R, we have now
      extended this work to identify the structural requirements of flavonoids to
      modify GLP-1R binding and signaling (cAMP formation and intracellular Ca(2+)
      mobilization) of each of the GLP-1R endogenous agonists, as well as the
      clinically used exogenous peptide mimetic exendin-4. This study identified a
      chemical series of hydroxyl flavonols with the ability to selectively augment
      calcium (Ca(2+)) signaling in a peptide agonist-specific manner, with effects
      only on truncated GLP-1 peptides [GLP-1(7-36)NH(2) and GLP-1(7-37)] and exendin
      4, but not on oxyntomodulin or full-length GLP-1 peptides [GLP-1(1-36)NH(2) and
      GLP-1(1-37)]. In addition, the 3-hydroxyl group on the flavone backbone (i.e., a
      flavonol) was essential for this activity, however insufficient on its own, to
      produce the allosteric effects. In contrast to hydroxyl flavonols, catechin had
      no effect on peptide-mediated Ca(2+) signaling but negatively modulated peptide
      mediated cAMP formation in a probe-dependent manner. These data represent a
      detailed examination of the action of different flavonoids on peptide agonists at
      the GLP-1R and may aid in the development of future small molecule compounds
      targeted at this receptor.

PMID- 21075840
TI  - Deuterium enrichment of vitamin A at the C20 position slows the formation of
      detrimental vitamin A dimers in wild-type rodents.
AB  - Degenerative eye diseases are the most common causes of untreatable blindness.
      Accumulation of lipofuscin (granular deposits) in the retinal pigment epithelium
      (RPE) is a hallmark of major degenerative eye diseases such as Stargardt disease,
      Best disease, and age-related macular degeneration. The intrinsic reactivity of
      vitamin A leads to its dimerization and to the formation of pigments such as A2E,
      and is believed to play a key role in the formation of ocular lipofuscin. We
      sought a clinically pragmatic method to slow vitamin A dimerization as a means to
      elucidate the pathogenesis of macular degenerations and to develop a therapeutic
      intervention. We prepared vitamin A enriched with the stable isotope deuterium at
      carbon twenty (C20-D(3)-vitamin A). Results showed that dimerization of deuterium
      enriched vitamin A was considerably slower than that of vitamin A at natural
      abundance as measured in vitro. Administration of C20-D(3)-vitamin A to wild-type
      rodents with no obvious genetic defects in vitamin A processing, slowed A2E
      biosynthesis. This study elucidates the mechanism of A2E biosynthesis and
      suggests that administration of C20-D(3)-vitamin A may be a viable, long-term
      approach to retard vitamin A dimerization and by extension, may slow lipofuscin
      deposition and the progression of common degenerative eye diseases.

PMID- 21075841
TI  - Spectroscopic studies on the [4Fe-4S] cluster in adenosine 5'-phosphosulfate
      reductase from Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis adenosine 5'-phosphosulfate reductase (MtAPR) is an
      iron-sulfur protein and a validated target to develop new antitubercular agents,
      particularly for the treatment of latent infection. The enzyme harbors a [4Fe
      4S](2+) cluster that is coordinated by four cysteinyl ligands, two of which are
      adjacent in the amino acid sequence. The iron-sulfur cluster is essential for
      catalysis; however, the precise role of the [4Fe-4S] cluster in APR remains
      unknown. Progress in this area has been hampered by the failure to generate a
      paramagnetic state of the [4Fe-4S] cluster that can be studied by electron
      paramagnetic resonance spectroscopy. Herein, we overcome this limitation and
      report the EPR spectra of MtAPR in the [4Fe-4S](+) state. The EPR signal is
      rhombic and consists of two overlapping S = &frac12; species. Substrate binding
      to MtAPR led to a marked increase in the intensity and resolution of the EPR
      signal and to minor shifts in principle g values that were not observed among a
      panel of substrate analogs, including adenosine 5'-diphosphate. Using site
      directed mutagenesis, in conjunction with kinetic and EPR studies, we have also
      identified an essential role for the active site residue Lys-144, whose side
      chain interacts with both the iron-sulfur cluster and the sulfate group of
      adenosine 5'-phosphosulfate. The implications of these findings are discussed
      with respect to the role of the iron-sulfur cluster in the catalytic mechanism of
      APR.

PMID- 21075842
TI  - NMR analyses of the Gbetagamma binding and conformational rearrangements of the
      cytoplasmic pore of G protein-activated inwardly rectifying potassium channel 1
      (GIRK1).
AB  - G protein-activated inwardly rectifying potassium channel (GIRK) plays crucial
      roles in regulating heart rate and neuronal excitability in eukaryotic cells.
      GIRK is activated by the direct binding of heterotrimeric G protein betagamma
      subunits (Gbetagamma) upon stimulation of G protein-coupled receptors, such as M2
      acetylcholine receptor. The binding of Gbetagamma to the cytoplasmic pore (CP)
      region of GIRK causes structural rearrangements, which are assumed to open the
      transmembrane ion gate. However, the crucial residues involved in the Gbetagamma
      binding and the structural mechanism of GIRK gating have not been fully
      elucidated. Here, we have characterized the interaction between the CP region of
      GIRK and Gbetagamma, by ITC and NMR. The ITC analyses indicated that four
      Gbetagamma molecules bind to a tetramer of the CP region of GIRK with a
      dissociation constant of 250 MUM. The NMR analyses revealed that the Gbetagamma
      binding site spans two neighboring subunits of the GIRK tetramer, which causes
      conformational rearrangements between subunits. A possible binding mode and
      mechanism of GIRK gating are proposed.

PMID- 21075843
TI  - Inhibition of proprotein convertase SKI-1 blocks transcription of key
      extracellular matrix genes regulating osteoblastic mineralization.
AB  - Mineralization, a characteristic phenotypic property of osteoblastic lineage
      cells, was blocked by 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride
      (AEBSF) and decanoyl-Arg-Arg-Leu-Leu-chloromethyl ketone (dec-RRLL-cmk),
      inhibitors of SKI-1 (site 1; subtilisin kexin like-1) protease. Because SKI-1 is
      required for activation of SREBP and CREB (cAMP-response element-binding
      protein)/ATF family transcription factors, we tested the effect of these
      inhibitors on gene expression. AEBSF decreased expression of 140 genes by 1.5-3.0
      fold including Phex, Dmp1, COL1A1, COL11A1, and fibronectin. Direct comparison of
      AEBSF and dec-RRLL-cmk, a more specific SKI-1 inhibitor, demonstrated that
      expression of Phex, Dmp1, COL11A1, and fibronectin was reduced by both, whereas
      COL1A2 and HMGCS1 were reduced only by AEBSF. AEBSF and dec-RRLL-cmk decreased
      the nuclear content of SKI-1-activated forms of transcription factors SREBP-1,
      SREBP-2, and OASIS. In contrast to AEBSF, the actions of dec-RRLL-cmk represent
      the sum of its direct actions on SKI-1 and indirect actions on caspase-3.
      Specifically, dec-RRLL-cmk reduced intracellular caspase-3 activity by blocking
      the formation of activated 19-kDa caspase-3. Conversely, overexpression of SKI-1
      activated SREBP-1a and CREB-H in UMR106-01 osteoblastic cells increased the
      number of mineralized foci and altered their morphology to yield mineralization
      nodules, respectively. In summary, SKI-1 regulates the activation of
      transmembrane transcription factor precursors required for expression of key
      genes required for mineralization of osteoblastic cultures in vitro and bone
      formation in vivo. Our results indicate that the differentiated phenotype of
      osteoblastic cells and possibly osteocytes depends upon the non-apoptotic actions
      of SKI-1.

PMID- 21075844
TI  - Serglycin is a major proteoglycan in polarized human endothelial cells and is
      implicated in the secretion of the chemokine GROalpha/CXCL1.
AB  - Proteoglycan (PG) expression was studied in primary human umbilical vein
      endothelial cells (HUVEC). RT-PCR analyses showed that the expression of the PG
      serglycin core protein was much higher than that of the extracellular matrix PG
      decorin and the cell surface PG syndecan-1. PG biosynthesis was further studied
      by biosynthetic [(35)S]sulfate labeling of polarized HUVEC. Interestingly, a
      major part of (35)S-PGs was secreted to the apical medium. A large portion of
      these PGs was trypsin-resistant, a typical feature of serglycin. The trypsin
      resistant PGs were mainly of the chondroitin/dermatan sulfate type but also
      contained a minor heparan sulfate component. Secreted serglycin was identified by
      immunoprecipitation as a PG with a core protein of ~30 kDa. Serglycin was
      furthermore shown to be present in perinuclear regions and in two distinct types
      of vesicles throughout the cytoplasm using immunocytochemistry. To search for
      possible serglycin partner molecules, HUVEC were stained for the chemokine growth
      related oncogene alpha (GROalpha/CXCL1). Co-localization with serglycin could be
      demonstrated, although not in all vesicles. Serglycin did not show overt co
      localization with tissue-type plasminogen activator-positive vesicles. When PG
      biosynthesis was abrogated using benzyl-beta-D-xyloside, serglycin secretion was
      decreased, and the number of vesicles with co-localized serglycin and GROalpha
      was reduced. The level of GROalpha in the apical medium was also reduced after
      xyloside treatment. Together, these findings indicate that serglycin is a major
      PG in human endothelial cells, mainly secreted to the apical medium and
      implicated in chemokine secretion.

PMID- 21075845
TI  - Envelope lipid-packing as a critical factor for the biological activity and
      stability of alphavirus particles isolated from mammalian and mosquito cells.
AB  - Alphaviruses are enveloped arboviruses. The viral envelope is derived from the
      host cell and is positioned between two icosahedral protein shells (T = 4).
      Because the viral envelope contains glycoproteins involved in cell recognition
      and entry, the integrity of the envelope is critical for the success of the early
      events of infection. Differing levels of cholesterol in different hosts leads to
      the production of alphaviruses with distinct levels of this sterol loaded in the
      envelope. Using Mayaro virus, a New World alphavirus, we investigated the role of
      cholesterol on the envelope of alphavirus particles assembled in either mammalian
      or mosquito cells. Our results show that although quite different in their
      cholesterol content, Mayaro virus particles obtained from both cells share a
      similar high level of lateral organization in their envelopes. This organization,
      as well as viral stability and infectivity, is severely compromised when
      cholesterol is depleted from the envelope of virus particles isolated from
      mammalian cells, but virus particles isolated from mosquito cells are relatively
      unaffected by cholesterol depletion. We suggest that it is not cholesterol
      itself, but rather the organization of the viral envelope, that is critical for
      the biological activity of alphaviruses.

PMID- 21075846
TI  - The proprotein convertase PC7: unique zymogen activation and trafficking
      pathways.
AB  - The zymogen activation mechanism and physiological functions of the most ancient
      and highly conserved basic amino acid-specific proprotein convertase 7 (PC7) are
      not known. Herein, we characterized the biosynthesis, subcellular localization,
      and trafficking of the membrane-bound full-length rat and human PC7. The
      prosegment of PC7 is primarily secreted alone as a non-inhibitory protein via the
      conventional, Golgi-dependent, secretory pathway. Mature PC7 is partially
      sulfated and thus reaches the cell surface via the conventional route. However, a
      fraction of PC7 reaches the cell surface through a brefeldin A- and COPII
      independent unconventional secretory pathway. The latter trafficking may explain
      the rapid (<10 min) transit of a fraction of PC7 from the ER to the cell surface.
      Electron microscopy further confirmed the localization of PC7 to the cell surface
      of HEK293 cells. Within the cytosolic tail, only two cysteines (Cys(699) and
      Cys(704)) are palmitoylated, but this modification does not affect the choice of
      trafficking pathway. Swapping the transmembrane-cytosolic tail (TMCT) sequences
      of the convertases Furin and PC7 revealed that PC7(TMCT-Furin) is much more
      sulfated and hence traffics more efficiently through the conventional secretory
      pathway. In contrast, the Furin(TMCT-PC7) is no longer sulfated and thus reaches
      the cell surface by the unconventional pathway. Because trafficking of PC7(CT
      Furin) and Furin(CT-PC7) resemble their wild type counterparts, we deduce that
      the transmembrane domain of PC7 regulates the sorting of PC7 toward the
      unconventional secretory pathway. In conclusion, PC7 is distinct from other
      proprotein convertases in its zymogen activation, subcellular localization, and
      trafficking.

PMID- 21075847
TI  - Sts1 plays a key role in targeting proteasomes to the nucleus.
AB  - The evidence that nuclear proteins can be degraded by cytosolic proteasomes has
      received considerable experimental support. However, the presence of proteasome
      subunits in the nucleus also suggests that protein degradation could occur within
      this organelle. We determined that Sts1 can target proteasomes to the nucleus and
      facilitate the degradation of a nuclear protein. Specific sts1 mutants showed
      reduced nuclear proteasomes at the nonpermissive temperature. In contrast, high
      expression of Sts1 increased the levels of nuclear proteasomes. Sts1 targets
      proteasomes to the nucleus by interacting with Srp1, a nuclear import factor that
      binds nuclear localization signals. Deletion of the NLS in Sts1 prevented its
      interaction with Srp1 and caused proteasome mislocalization. In agreement with
      this observation, a mutation in Srp1 that weakened its interaction with Sts1 also
      reduced nuclear targeting of proteasomes. We reported that Sts1 could suppress
      growth and proteolytic defects of rad23Delta rpn10Delta. We show here that Sts1
      suppresses a previously undetected proteasome localization defect in this mutant.
      Taken together, these findings explain the suppression of rad23Delta rpn10Delta
      by Sts1 and suggest that the degradation of nuclear substrates requires efficient
      proteasome localization.

PMID- 21075848
TI  - Diminished paracrine regulation of the epithelial Na+ channel by purinergic
      signaling in mice lacking connexin 30.
AB  - We tested whether ATP release through Connexin 30 (Cx30) is part of a local
      purinergic regulatory system intrinsic to the aldosterone-sensitive distal
      nephron (ASDN) important for proper control of sodium excretion; if changes in
      sodium intake influence ATP release via Cx30; and if this allows a normal ENaC
      response to changes in systemic sodium levels. In addition, we define the
      consequences of disrupting ATP regulation of ENaC in Cx30(-/-) mice. Urinary ATP
      levels in wild-type mice increase with sodium intake, being lower and less
      dependent on sodium intake in Cx30(-/-) mice. Loss of inhibitory ATP regulation
      causes ENaC activity to be greater in Cx30(-/-) versus wild-type mice,
      particularly with high sodium intake. This results from compromised ATP release
      rather than end-organ resistance: ENaC in Cx30(-/-) mice responds to exogenous
      ATP. Thus, loss of paracrine ATP feedback regulation of ENaC in Cx30(-/-) mice
      disrupts normal responses to changes in sodium intake. Consequently, ENaC is
      hyperactive in Cx30(-/-) mice lowering sodium excretion particularly during
      increases in sodium intake. Clamping mineralocorticoids high in Cx30(-/-) mice
      fed a high sodium diet causes a marked decline in renal sodium excretion. This is
      not the case in wild-type mice, which are capable of undergoing aldosterone
      escape. This loss of the ability of ENaC to respond to changes in sodium levels
      contributes to salt-sensitive hypertension in Cx30(-/-) mice.

PMID- 21075849
TI  - Roles of Dim2 in ribosome assembly.
AB  - In eukaryotes, ribosome assembly requires hundreds of conserved essential
      proteins not present in the mature particle. Despite their importance, the
      function of most factors remains unknown. This is because protein deletion often
      affects the composition of the entire particle. Additionally, many proteins are
      present in assembling ribosomes for extended times, which makes it difficult to
      pinpoint their role to a particular step. Here we have combined classical yeast
      biochemistry with experiments using recombinant proteins and RNA to study the
      role of Dim2 and its interaction with Nob1, the nuclease that generates the 3'
      end of 18 S rRNA. Analysis of Dim2 mutants in which the interaction with Nob1 is
      disrupted demonstrates that this interaction between Dim2 and Nob1 is essential
      for optimal growth, and RNA binding experiments show that Dim2 increases Nob1 RNA
      affinity. Furthermore, our data indicate that Dim2 helps regulate Nob1 cleavage
      activity at the 3'-end of 18 S rRNA, as point mutants where this interaction is
      abolished in vitro accumulate pre-ribosomes containing Nob1 and 20 S rRNA in
      vivo. Interestingly, the site of interaction with Nob1 is mapped to the canonical
      RNA binding surface of a KH-like domain in Dim2, providing another example where
      an RNA-binding domain can be repurposed for protein interactions.

PMID- 21075850
TI  - The transcription elongation factor Bur1-Bur2 interacts with replication protein
      A and maintains genome stability during replication stress.
AB  - Multiple DNA-associated processes such as DNA repair, replication, and
      recombination are crucial for the maintenance of genome integrity. Here, we show
      a novel interaction between the transcription elongation factor Bur1-Bur2 and
      replication protein A (RPA), the eukaryotic single-stranded DNA-binding protein
      with functions in DNA repair, recombination, and replication. Bur1 interacted via
      its C-terminal domain with RPA, and bur1-DeltaC mutants showed a deregulated DNA
      damage response accompanied by increased sensitivity to DNA damage and
      replication stress as well as increased levels of persisting Rad52 foci.
      Interestingly, the DNA damage sensitivity of an rfa1 mutant was suppressed by
      bur1 mutation, further underscoring a functional link between these two protein
      complexes. The transcription elongation factor Bur1-Bur2 interacts with RPA and
      maintains genome integrity during DNA replication stress.

PMID- 21075851
TI  - Anti-inflammatory role of microsomal prostaglandin E synthase-1 in a model of
      neuroinflammation.
AB  - A major immunological response during neuroinflammation is the activation of
      microglia, which subsequently release proinflammatory mediators such as
      prostaglandin E(2) (PGE(2)). Besides its proinflammatory properties,
      cyclooxygenase-2 (COX-2)-derived PGE(2) has been shown to exhibit anti
      inflammatory effects on innate immune responses. Here, we investigated the role
      of microsomal PGE(2) synthase-1 (mPGES-1), which is functionally coupled to COX
      2, in immune responses using a model of lipopolysaccharide (LPS)-induced spinal
      neuroinflammation. Interestingly, we found that activation of E-prostanoid (EP)2
      and EP4 receptors, but not EP1, EP3, PGI(2) receptor (IP), thromboxane A(2)
      receptor (TP), PGD(2) receptor (DP), and PGF(2) receptor (FP), efficiently
      blocked LPS-induced tumor necrosis factor alpha (TNFalpha) synthesis and COX-2
      and mPGES-1 induction as well as prostaglandin synthesis in spinal cultures. In
      vivo, spinal EP2 receptors were up-regulated in microglia in response to
      intrathecally injected LPS. Accordingly, LPS priming reduced spinal synthesis of
      TNFalpha, interleukin 1beta (IL-1beta), and prostaglandins in response to a
      second intrathecal LPS injection. Importantly, this reduction was only seen in
      wild-type but not in mPGES-1-deficient mice. Furthermore, intrathecal application
      of EP2 and EP4 agonists as well as genetic deletion of EP2 significantly reduced
      spinal TNFalpha and IL-1beta synthesis in mPGES-1 knock-out mice after LPS
      priming. These data suggest that initial inflammation prepares the spinal cord
      for a negative feedback regulation by mPGES-1-derived PGE(2) followed by EP2
      activation, which limits the synthesis of inflammatory mediators during chronic
      inflammation. Thus, our data suggest a role of mPGES-1-derived PGE(2) in
      resolution of neuroinflammation.

PMID- 21075853
TI  - Cellular ATP synthesis mediated by type III sodium-dependent phosphate
      transporter Pit-1 is critical to chondrogenesis.
AB  - Disturbed endochondral ossification in X-linked hypophosphatemia indicates an
      involvement of P(i) in chondrogenesis. We studied the role of the sodium
      dependent P(i) cotransporters (NPT), which are a widely recognized regulator of
      cellular P(i) homeostasis, and the downstream events in chondrogenesis using Hyp
      mice, the murine homolog of human X-linked hypophosphatemia. Hyp mice showed
      reduced apoptosis and mineralization in hypertrophic cartilage. Hyp chondrocytes
      in culture displayed decreased apoptosis and mineralization compared with WT
      chondrocytes, whereas glycosaminoglycan synthesis, an early event in
      chondrogenesis, was not altered. Expression of the type III NPT Pit-1 and P(i)
      uptake were diminished, and intracellular ATP levels were also reduced in
      parallel with decreased caspase-9 and caspase-3 activity in Hyp chondrocytes. The
      competitive NPT inhibitor phosphonoformic acid and ATP synthesis inhibitor 3
      bromopyruvate disturbed endochondral ossification with reduced apoptosis in vivo
      and suppressed apoptosis and mineralization in conjunction with reduced P(i)
      uptake and ATP synthesis in WT chondrocytes. Overexpression of Pit-1 in Hyp
      chondrocytes reversed P(i) uptake and ATP synthesis and restored apoptosis and
      mineralization. Our results suggest that cellular ATP synthesis consequent to
      P(i) uptake via Pit-1 plays an important role in chondrocyte apoptosis and
      mineralization, and that chondrogenesis is ATP-dependent.

PMID- 21075852
TI  - Regulatory effects of ribosomal S6 kinase 1 (RSK1) in IFNlambda signaling.
AB  - Although the mechanisms of generation of signals that control transcriptional
      activation of Type III IFN (IFNlambda)-regulated genes have been identified, very
      little is known about the mechanisms by which the IFNlambda receptor generates
      signals for mRNA translation of IFNlambda-activated genes. We provide evidence
      that IFNlambda activates the p90 ribosomal protein S6 kinase 1 (RSK1) and its
      downstream effector, initiation factor eIF4B. Prior to its engagement by the
      IFNlambda receptor, the non-active form of RSK1 is present in a complex with the
      translational repressor 4E-BP1 in IFNlambda-sensitive cells. IFNlambda-inducible
      phosphorylation/activation of RSK1 results in its dissociation from 4E-BP1 at the
      same time that 4E-BP1 dissociates from eIF4E to allow formation of eIF4F and
      initiation of cap-dependent translation. Our studies demonstrate that such
      IFNlambda-dependent engagement of RSK1 is essential for up-regulation of
      p21(WAF1/CIP1) expression, suggesting a mechanism for generation of growth
      inhibitory responses. Altogether, our data provide evidence for a critical role
      for the activated RSK1 in IFNlambda signaling.

PMID- 21075854
TI  - The polypeptide binding conformation of calreticulin facilitates its cell-surface
      expression under conditions of endoplasmic reticulum stress.
AB  - We define two classes of calreticulin mutants that retain glycan binding
      activity; those that display enhanced or reduced polypeptide-specific chaperone
      activity, due to conformational effects. Under normal conditions, neither set of
      mutants significantly impacts the ability of calreticulin to mediate assembly and
      trafficking of major histocompatibility complex class I molecules, which are
      calreticulin substrates. However, in cells treated with thapsigargin, which
      depletes endoplasmic reticulum calcium, major histocompatibility complex class I
      trafficking rates are accelerated coincident with calreticulin secretion, and
      detection of cell-surface calreticulin is dependent on its polypeptide binding
      conformations. Together, these findings identify a site on calreticulin that is
      an important determinant of the induction of its polypeptide binding conformation
      and demonstrate the relevance of the polypeptide binding conformations of
      calreticulin to endoplasmic reticulum stress-induced interactions.

PMID- 21075856
TI  - A new measure of alcohol affordability for the UK.
AB  - AIMS: To present revisions to the official UK measure of alcohol affordability
      published by the National Health Service (NHS) Information Centre. The revisions
      address the following problems in the official measure:(a) The income measure
      used in the calculation is a measure of the income for the whole population of
      the UK, not income per capita. (b) The income measure includes 'imaginary' items,
      namely imputed rentals and attributed income from insurance policies. (c) The
      income measure is inconsistent in its treatment of housing costs. (d) The
      adjustment for inflation makes the measure unnecessarily complex and can have
      counter-intuitive effects. METHODS: The revised measure has the same essential
      structure as the NHS measure, being the ratio of income to price of alcohol.
      Adjustments were applied to official income figures, and adjustments for
      inflation were removed. RESULTS: The revised measure shows that affordability has
      levelled off since 2003, in contrast to the NHS measure, which shows it
      continuing to rise until 2008. CONCLUSION: The revised measure corrects a basic
      error of failing to divide total income for the UK by number of people in the
      population. This alters the measure but is more correct. Further improvements
      result in a measure that correlates more closely with UK alcohol consumption over
      the last decade.

PMID- 21075855
TI  - Gender differences in drinking practices in middle aged and older Russians.
AB  - AIMS: The study investigated gender differences in drinking patterns and the
      reasons behind them among men and women in the Russian city of Novosibirsk.
      METHODS: A mixed method, combining quantitative and qualitative data, was
      conducted based on the Health, Alcohol and Psychosocial factors In Eastern Europe
      cohort study. The quantitative study included 4268 men and 5094 women aged 45-69
      years; of those, 20 men and 24 women completed an in-depth interview. RESULTS:
      The quantitative data revealed a large gap in drinking patterns in general
      between genders. Women drank less often and much smaller quantities than that of
      men. For example, 19% of men, vs. 1% of women, were classified as problem
      drinkers (two or more positive answers on the CAGE questionnaire). These
      differences were not explained by socioeconomic factors. Qualitative data have
      shown that gender roles and a traditional culture around women's and men's
      drinking were the main reasons for the reported drinking behaviour, whereby women
      were consistently expected to drink much less than men in terms of preference for
      strong beverages, drinking frequency and quantity of alcohol consumed.
      CONCLUSION: The study confirmed that large differences exist between Russian
      men's and women's drinking; these differences may be largely explained by gender
      roles.

PMID- 21075857
TI  - Molecular classification of low-grade diffuse gliomas.
AB  - The current World Health Organization classification recognizes three
      histological types of grade II low-grade diffuse glioma (diffuse astrocytoma,
      oligoastrocytoma, and oligodendroglioma). However, the diagnostic criteria, in
      particular for oligoastrocytoma, are highly subjective. The aim of our study was
      to establish genetic profiles for diffuse gliomas and to estimate their
      predictive impact. In this study, we screened 360 World Health Organization grade
      II gliomas for mutations in the IDH1, IDH2, and TP53 genes and for 1p/19q loss
      and correlated these with clinical outcome. Most tumors (86%) were characterized
      genetically by TP53 mutation plus IDH1/2 mutation (32%), 1p/19q loss plus IDH1/2
      mutation (37%), or IDH1/2 mutation only (17%). TP53 mutations only or 1p/19q loss
      only was rare (2 and 3%, respectively). The median survival of patients with TP53
      mutation +/- IDH1/2 mutation was significantly shorter than that of patients with
      1p/19q loss +/- IDH1/2 mutation (51.8 months vs. 58.7 months, respectively; P =
      0.0037). Multivariate analysis with adjustment for age and treatment confirmed
      these results (P = 0.0087) and also revealed that TP53 mutation is a significant
      prognostic marker for shorter survival (P = 0.0005) and 1p/19q loss for longer
      survival (P = 0.0002), while IDH1/2 mutations are not prognostic (P = 0.8737).
      The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and
      1p/19q loss has power similar to histological classification and avoids the
      ambiguity inherent to the diagnosis of oligoastrocytoma.

PMID- 21075859
TI  - Dopamine, by acting through its D2 receptor, inhibits insulin-like growth factor
      I (IGF-I)-induced gastric cancer cell proliferation via up-regulation of Kruppel
      like factor 4 through down-regulation of IGF-IR and AKT phosphorylation.
AB  - The overexpression of insulin-like growth factor receptor-I (IGF-IR) and the
      activation of its signaling pathways both play critical roles in the development
      and progression of gastric cancer. Dopamine (DA), a major enteric
      neurotransmitter, has been reported to have a wide variety of physiological
      functions in the gastrointestinal tract, including the stomach. We have
      previously reported that both DA and tyrosine hydroxylase, the rate-limiting
      enzyme required for the synthesis of DA, are lost in malignant gastric tissues.
      The effect of this loss of DA on IGF-IR-induced growth of gastric cancer has not
      yet been elucidated; we therefore investigated the role of DA, if any, on IGF-IR
      induced proliferation of malignant gastric cells. There was a significant
      increase in the expression of phosphorylated IGF-IR and its downstream signaling
      molecule AKT in human malignant gastric tissues compared with normal nonmalignant
      tissues. Furthermore, to determine whether this loss of DA has any effect on the
      activation of IGF-IR signaling pathways in malignant gastric tumors, in vitro
      experiments were undertaken, using AGS gastric cancer cells. Our results
      demonstrated that DA acting through its D(2) receptor, inhibits IGF-I-induced
      proliferation of AGS cells by up-regulating KLF4, a negative regulator of the
      cell cycle through down regulation of IGF-IR and AKT phosphorylation. Our results
      suggest that DA is an important regulator of IGF-IR function in malignant gastric
      cancer cells.

PMID- 21075858
TI  - Plakoglobin rescues adhesive defects induced by ectodomain truncation of the
      desmosomal cadherin desmoglein 1: implications for exfoliative toxin-mediated
      skin blistering.
AB  - Desmoglein 1 (Dsg1) is a desmosomal cadherin that is essential to epidermal
      integrity. In the blistering diseases bullous impetigo and staphylococcal scalded
      skin syndrome, pathogenesis depends on cleavage of Dsg1 by a bacterial protease,
      exfoliative toxin A, which removes residues 1 to 381 of the Dsg1 ectodomain.
      However, the cellular responses to Dsg1 cleavage that precipitate keratinocyte
      separation to induce blister formation are unknown. Here, we show that ectodomain
      deleted Dsg1 (Delta381-Dsg1) mimics the toxin-cleaved cadherin, disrupts
      desmosomes, and reduces the mechanical integrity of keratinocyte sheets. In
      addition, we demonstrate that truncated Dsg1 remains associated with its catenin
      partner, plakoglobin, and causes a reduction in the levels of endogenous
      desmosomal cadherins in a dose-dependent manner, leading us to hypothesize that
      plakoglobin sequestration by truncated Dsg1 destabilizes other cadherins.
      Accordingly, a triple-point mutant of the ectodomain-deleted cadherin, which is
      uncoupled from plakoglobin, does not impair adhesion, indicating that this
      interaction is essential to the pathogenic potential of truncated Dsg1. Moreover,
      we demonstrate that increasing plakoglobin levels rescues cadherin expression,
      desmosome organization, and functional adhesion in cells expressing Delta381-Dsg1
      or treated with exfoliative toxin A. Finally, we report that histone deacetylase
      inhibition up-regulates desmosomal cadherins and prevents the loss of adhesion
      induced by Dsg1 truncation. These findings further our understanding of the
      mechanism of exfoliative toxin-induced pathology and suggest novel strategies to
      suppress blistering in bulbous impetigo and staphylococcal scalded-skin syndrome.

PMID- 21075861
TI  - Role of nerve growth factor in ozone-induced neural responses in early postnatal
      airway development.
AB  - Airway neural plasticity contributes to the process of airway remodeling in
      response to airway irritants. However, the mechanisms of neural remodeling in the
      airways during the early postnatal period, when responses to airway irritation
      may be most sensitive, have not been characterized. This study used a rat model
      to examine a possible mechanism of ozone (O(3))-induced neural
      hyperresponsiveness during a critical period of developmental, postnatal day (PD)
      6, that may be mediated by the neurotrophin nerve growth factor (NGF), resulting
      in an enhanced release of inflammatory neuropeptide substance P (SP) from airway
      nerves. Rat pups between PD6-PD28 were killed 24 hours after exposure to O(3) (2
      ppm, 3 hours) or filtered air (FA), to establish a timeline of NGF synthesis, or
      else they were exposed to O(3) or NGF on PD6 or PD21 and re-exposed to O(3) on
      PD28, and killed on PD29. Measurement endpoints included NGF mRNA in tracheal
      epithelial cells, NGF protein in bronchoalveolar lavage fluid, airway SP-nerve
      fiber density (NFD), and SP-positive airway neurons in vagal ganglia. Acute
      exposure to O(3) increased NGF in bronchoalveolar lavage fluid on PD10 and PD15,
      and mRNA expression in epithelial cells on PD6, compared with FA controls. NGF
      protein and mRNA expression in the O(3)-PD6/O(3)-PD28 groups were significantly
      higher than in the O(3)-PD21/O(3)-PD28 and O(3)-PD6/FA-PD28 groups. NGF-PD6/O(3)
      PD28 increased the SP innervation of airway smooth muscle and SP-positive sensory
      neurons, compared with the NGF-PD21/O(3)-PD28 or NGF-PD6/FA-PD28 groups. NGF
      enhanced sensory innervation, which may mediate acute responses or prolong
      sensitivity to O(3) during early life. The model may be relevant in O(3)
      responses during early childhood.

PMID- 21075862
TI  - Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary
      hypertension.
AB  - Remodeling of the pulmonary arteries is a common feature among the heterogeneous
      disorders that cause pulmonary hypertension. In these disorders, the remodeled
      pulmonary arteries often demonstrate inflammation and an accumulation of
      pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue
      secretes multiple bioactive mediators (adipokines) that can influence both
      inflammation and remodeling, suggesting that adipokines may contribute to the
      development of pulmonary hypertension. We recently reported on a model of
      pulmonary hypertension induced by vascular inflammation, in which a deficiency of
      the adipokine adiponectin (APN) was associated with the extensive proliferation
      of PASMCs and increased pulmonary artery pressures. Based on these data, we
      hypothesize that APN can suppress pulmonary hypertension by directly inhibiting
      the proliferation of PASMCs. Here, we tested the effects of APN overexpression on
      pulmonary arterial remodeling by using APN-overexpressing mice in a model of
      pulmonary hypertension induced by inflammation. Consistent with our hypothesis,
      mice that overexpressed APN manfiested reduced pulmonary hypertension and
      remodeling compared with wild-type mice, despite developing similar levels of
      pulmonary vascular inflammation in the model. The overexpression of APN was also
      protective in a hypoxic model of pulmonary hypertension. Furthermore, APN
      suppressed the proliferation of PASMCs, and reduced the activity of the serum
      response factor-serum response element pathway, which is a critical signaling
      pathway for smooth muscle cell proliferation. Overall, these data suggest that
      APN can regulate pulmonary hypertension and pulmonary arterial remodeling through
      its direct effects on PASMCs. Hence, the activation of APN-like activity in the
      pulmonary vasculature may be beneficial in pulmonary hypertension.

PMID- 21075863
TI  - Cloning and characterization of human MUC19 gene.
AB  - The most recently discovered gel-forming mucin, MUC19, is expressed in both
      salivary glands and tracheal submucosal glands. We previously cloned the 3'-end
      partial sequence (AY236870), and here report the complete sequencing of the
      entire MUC19 cDNA. One highly variable region (HVR) was discovered in the 5' end
      of MUC19. A total of 20 different splicing variants were detected in HVR, and 18
      variants are able to translate into proteins along with the rest of the MUC19
      sequence. The longest variant of MUC19 consists of 182 exons, with a transcript
      of approximately 25 kb. A central exon of approximately 12 kb contains highly
      repetitive sequences and has no intron interruption. The deduced MUC19 protein
      has the bona fide gel-forming mucin structure, VWD-VWD-VWD-"threonine/serine-rich
      repeats"-VWC-CT. An unusual structural feature of MUC19, which is lacking in
      other gel-forming mucins, is its long amino terminus upstream of the first VWD
      domain. The long amino terminus is mostly translated from the sequences in HVR,
      and contains serine-rich repetitive sequences. To validate the integrity of the
      MUC19 sequence, primers from both the 3' and 5' end were used to demonstrate a
      similar tissue expression pattern of MUC19 in trachea and salivary glands. In
      addition, antibodies were developed against either the amino (N) or carboxy (C)
      terminus of MUC19, and similar antibody staining patterns were observed in both
      salivary and tracheal submucosal glands. In conclusion, we have cloned and
      elucidated the entire MUC19 gene, which will facilitate understanding of the
      function and regulation of this important, yet understudied, mucin gene in airway
      diseases.

PMID- 21075867
TI  - Illiteracy: the neuropsychology of cognition without reading.
AB  - Illiterates represent a significant proportion of the world's population. Written
      language not only plays a role in mediating cognition, but also extends our
      knowledge of the world. Two major reasons for illiteracy can be distinguished,
      social (e.g., absence of schools), and personal (e.g., learning difficulties).
      Without written language, our knowledge of the external world is partially
      limited by immediate sensory information and concrete environmental conditions.
      Literacy is significantly associated with virtually all neuropsychological
      measures, even though the correlation between education and neuropsychological
      test scores depends on the specific test. The impact of literacy is reflected in
      different spheres of cognitive functioning. Learning to read reinforces and
      modifies certain fundamental abilities, such as verbal and visual memory,
      phonological awareness, and visuospatial and visuomotor skills. Functional
      imaging studies are now demonstrating that literacy and education influence the
      pathways used by the brain for problem-solving. The existence of partially
      specific neuronal networks as a probable consequence of the literacy level
      supports the hypothesis that education impacts not only the individual's day-to
      day strategies, but also the brain networks. A review of the issues related to
      dementia in illiterates is presented, emphasizing that the association between
      the education level and age-related cognitive changes and education remains
      controversial. The analysis of the impact of illiteracy on neuropsychological
      test performance represents a crucial approach to understanding human cognition
      and its brain organization under normal and abnormal conditions.

PMID- 21075868
TI  - Strategic directions for health promotion.

PMID- 21075869
TI  - Cardiac inflammation contributes to changes in the extracellular matrix in
      patients with heart failure and normal ejection fraction.
AB  - BACKGROUND: The pathophysiology of heart failure with normal ejection fraction
      (HFNEF) is still under discussion. Here we report the influence of cardiac
      inflammation on extracellular matrix (ECM) remodeling in patients with HFNEF.
      METHODS AND RESULTS: We investigated left ventricular systolic and diastolic
      function in 20 patients with HFNEF and 8 control patients by conductance catheter
      methods and echocardiography. Endomyocardial biopsy samples were also obtained,
      and ECM proteins as well as cardiac inflammatory cells were investigated. Primary
      human cardiac fibroblasts were outgrown from the endomyocardial biopsy samples to
      investigate the gene expression of ECM proteins after stimulation with
      transforming growth factor-beta. Diastolic dysfunction was present in the HFNEF
      patients compared with the control patients. In endomyocardial biopsy samples
      from HFNEF patients, we found an accumulation of cardiac collagen, which was
      accompanied by a decrease in the major collagenase system (matrix
      metalloproteinase-1) in the heart. Moreover, a subset of inflammatory cells,
      which expressed the profibrotic growth factor transforming growth factor-beta,
      could be documented in the HFNEF patients. Stimulation of primary human cardiac
      fibroblasts from HFNEF patients with transforming growth factor-beta resulted in
      transdifferentiation of fibroblasts to myofibroblasts, which produced more
      collagen and decreased the amount of matrix metalloproteinase-1, the major
      collagenase in the human heart. A positive correlation between cardiac collagen,
      as well as the amount of inflammatory cells, and diastolic dysfunction was
      evident and suggests a direct influence of inflammation on fibrosis triggering
      diastolic dysfunction. CONCLUSIONS: Cardiac inflammation contributes to diastolic
      dysfunction in HFNEF by triggering the accumulation of ECM.

PMID- 21075870
TI  - Corin is present in the normal human heart, kidney, and blood, with pro-B-type
      natriuretic peptide processing in the circulation.
AB  - BACKGROUND: B-type natriuretic peptide (BNP), which is activated in heart failure
      (HF), is processed to an active form by corin. The corin gene is expressed in the
      human heart and kidney, but corin protein expression in the heart, kidney, and
      circulation, along with whether proBNP is processed by circulating corin, remains
      unknown. METHODS: We examined corin protein expression by immunostaining and
      Western blot in human heart and kidney, and we assessed the circulating corin
      concentration by ELISA. We examined histidine-tagged (His-tag) proBNP(1-108)
      processing in serum and plasma by immunoprecipitation and Western blot and
      sequenced the processed form. RESULTS: Normal human heart and kidney displayed
      the presence of corin, especially in cells around the vasculature. Both corin and
      proBNP(1-108) were present in the plasma of healthy human subjects, with
      circulating corin significantly higher in men than women (P < 0.0001) and a
      positive correlation of corin to age (P = 0.0497, r = 0.27). In fresh normal
      plasma and serum, His-tag proBNP(1-108) was processed to a lower molecular weight
      form confirmed to be BNP. Processed BNP was higher in men than women (P = 0.041)
      and was positively correlated to plasma corin concentrations (P = 0.041, r =
      0.65). CONCLUSIONS: Our results support the concept that proBNP(1-108) may be
      processed outside of the heart in the circulation where the proprotein convertase
      is present. Moreover, sex may impact this process, since corin concentrations are
      higher in men. These findings may have important physiologic and pathophysiologic
      implications for the proBNP/corin system in the human.

PMID- 21075871
TI  - Colonization of tomato plants by Salmonella enterica is cultivar dependent, and
      type 1 trichomes are preferred colonization sites.
AB  - Nontyphoid salmonellosis caused by Salmonella enterica is the most common
      bacterial food-borne illness in humans, and fresh produce, including tomatoes, is
      a common vehicle. Accumulating data indicate that human enteric pathogenic
      bacteria, including S. enterica, interact actively with plants. Tomato plants
      were inoculated with S. enterica to evaluate plausible contamination routes and
      to determine if the tomato cultivar affects S. enterica colonization. S. enterica
      population levels on tomato leaves were cultivar dependent. S. enterica levels on
      Solanum pimpinellifolium (West Virginia 700 [WVa700]) were lower than on S.
      lycopersicum cultivars. S. enterica preferentially colonized type 1 trichomes and
      rarely interacted with stomata, unlike what has been reported for cut lettuce
      leaves. Early S. enterica leaf colonization led to contamination of all fruit,
      with levels as high as 10(5) CFU per fruit. Reduced bacterial speck lesion
      formation correlated with reduced S. enterica populations in the phyllosphere.
      Tomato pedicels and calyxes also harbored large S. enterica populations following
      inoculation via contaminated water postharvest. WVa700 green fruit harbored
      significantly smaller S. enterica populations than did red fruit or S.
      lycopersicum fruit. We found that plants irrigated with contaminated water had
      larger S. enterica populations than plants grown from seeds planted in infested
      soil. However, both routes of contamination resulted in detectable S. enterica
      populations in the phyllosphere. Phyllosphere S. enterica populations pose a risk
      of fruit contamination and subsequent human disease. Restricting S. enterica
      phyllosphere populations may result in reduced fruit contamination. We have
      identified WVa700 as a tomato cultivar that can restrict S. enterica survival in
      the phyllosphere.

PMID- 21075872
TI  - Switch between life history strategies due to changes in glycolytic enzyme gene
      dosage in Saccharomyces cerevisiae.
AB  - Adaptation is the process whereby a population or species becomes better fitted
      to its habitat through modifications of various life history traits which can be
      positively or negatively correlated. The molecular factors underlying these
      covariations remain to be elucidated. Using Saccharomyces cerevisiae as a model
      system, we have investigated the effects on life history traits of varying the
      dosage of genes involved in the transformation of resources into energy. Changing
      gene dosage for each of three glycolytic enzyme genes (hexokinase 2,
      phosphoglucose isomerase, and fructose-1,6-bisphosphate aldolase) resulted in
      variation in enzyme activities, glucose consumption rate, and life history traits
      (growth rate, carrying capacity, and cell size). However, the range of effects
      depended on which enzyme was expressed differently. Most interestingly, these
      changes revealed a genetic trade-off between carrying capacity and cell size,
      supporting the discovery of two extreme life history strategies already described
      in yeast populations: the "ants," which have lower glycolytic gene dosage, take
      up glucose slowly, and have a small cell size but reach a high carrying capacity,
      and the "grasshoppers," which have higher glycolytic gene dosage, consume glucose
      more rapidly, and allocate it to a larger cell size but reach a lower carrying
      capacity. These results demonstrate antagonist pleiotropy for glycolytic genes
      and show that altered dosage of a single gene drives a switch between two life
      history strategies in yeast.

PMID- 21075873
TI  - Extracellular aldonolactonase from Myceliophthora thermophila.
AB  - Fungi secrete many different enzymes to deconstruct lignocellulosic biomass,
      including several families of hydrolases, oxidative enzymes, and many
      uncharacterized proteins. Here we describe the isolation, characterization, and
      primary sequence analysis of an extracellular aldonolactonase from the
      thermophilic fungus Myceliophthora thermophila (synonym Sporotrichum
      thermophile). The lactonase is a 48-kDa glycoprotein with a broad pH optimum. The
      enzyme catalyzes the hydrolysis of glucono-delta-lactone and cellobiono-delta
      lactone with an apparent second-order rate constant, k(cat)/K(m), of ~1 * 10(6)
      M(-1) s(-1) at pH 5.0 and 25 degrees C but is unable to hydrolyze xylono-gamma
      lactone or arabino-gamma-lactone. Sequence analyses of the lactonase show that it
      has distant homology to cis-carboxy-muconate lactonizing enzymes (CMLE) as well
      as 6-phosphogluconolactonases present in some bacteria. The M. thermophila genome
      contains two predicted extracellular lactonase genes, and expression of both
      genes is induced by the presence of pure cellulose. Homologues of the M.
      thermophila lactonase, which are also predicted to be extracellular, are present
      in nearly all known cellulolytic ascomycetes.

PMID- 21075875
TI  - Detection of bacterial indicators and human and bovine enteric viruses in surface
      water and groundwater sources potentially impacted by animal and human wastes in
      Lower Yakima Valley, Washington.
AB  - Tangential flow ultrafiltration (UF) was used to concentrate and recover
      bacterial indicators and enteric viruses from 100 liters of groundwater (GW; n =
      10) and surface water (SW; n = 11) samples collected in Lower Yakima Valley, WA.
      Human and bovine enteric viruses were analyzed in SW and GW concentrates by real
      time PCR by using integrated inhibition detection.

PMID- 21075876
TI  - Army ants harbor a host-specific clade of Entomoplasmatales bacteria.
AB  - In this article, we describe the distributions of Entomoplasmatales bacteria
      across the ants, identifying a novel lineage of gut bacteria that is unique to
      the army ants. While our findings indicate that the Entomoplasmatales are not
      essential for growth or development, molecular analyses suggest that this
      relationship is host specific and potentially ancient. The documented trends add
      to a growing body of literature that hints at a diversity of undiscovered
      associations between ants and bacterial symbionts.

PMID- 21075877
TI  - Effect of environmental factors and influence of rumen and hindgut biogeography
      on bacterial communities in steers.
AB  - Feces from cattle production are considered important sources of bacterial
      contamination of food and the environment. Little is known about the combined
      effects of arctic temperatures and fodder tannins on rumen and hindgut bacterial
      populations. Individual rumen liquor and rectal fecal samples from donor steers
      fed either alfalfa silage or sainfoin (Onobrychis viciifolia Scop.) silage and
      water ad libitum were collected weekly on the first three sampling days and
      fortnightly afterwards. The daily ambient temperatures were registered and
      averaged to weekly mean temperatures. Steers fed sainfoin silage had lower (P <
      0.05) concentrations of branched-chain volatile fatty acids (VFA) than those fed
      alfalfa silage. All VFA concentrations were higher (P < 0.001) in rumen liquor
      samples than in fecal samples. The interaction of sample type and diet showed a
      significant effect (P < 0.05) on the proportions of the bacterial community that
      were from the phyla Proteobacteria and Verrucomicrobia. Ambient temperature had
      an indirect effect (P < 0.05) on the phylum Firmicutes, as it affected its
      proportional balance. The bacterial population diversity in samples appeared to
      decrease concurrently with the ambient temperature. The phylum Firmicutes
      explained the first principal component at 64.83 and 42.58% of the total variance
      in rumen liquor and fecal samples, respectively. The sample type had a larger
      effect on bacterial communities than diet and temperature. Certain bacterial
      populations seemed to be better adapted than others to environmentally adverse
      conditions, such as less access time to nutrients due to higher motility and rate
      of passage of digesta caused by extreme temperatures, or antimicrobials such as
      tannins, possibly due to an influence of their biogeographical location within
      the gut.

PMID- 21075878
TI  - Autoregulation of lantibiotic bovicin HJ50 biosynthesis by the BovK-BovR two
      component signal transduction system in Streptococcus bovis HJ50.
AB  - Streptococcus bovis HJ50 produces a lacticin 481-like 33-amino-acid-residue
      lantibiotic, designated bovicin HJ50. bovK-bovR in the bovicin HJ50 biosynthetic
      gene cluster is predicted to be a two-component signal transduction system
      involved in sensing signals and regulating gene expression. Disruption of bovK or
      bovR resulted in the abrogation of bovicin HJ50 production, suggesting both genes
      play important roles in bovicin HJ50 biosynthesis. Addition of exogenous bovicin
      HJ50 peptide to cultures of a bovM mutant that lost the capability for bovicin
      HJ50 production and structural gene bovA transcription in S. bovis HJ50 induced
      dose-dependent transcription of the bovA gene, demonstrating that bovicin HJ50
      production was normally autoregulated. The transcription of bovA was no longer
      induced by bovicin HJ50 in bovK and bovR disruption mutants, suggesting that BovK
      BovR plays an essential role in the signal transduction regulating bovicin HJ50
      biosynthesis. A phosphorylation assay indicated that BovK has the ability to
      autophosphorylate and subsequently transfer the phosphoryl group to the
      downstream BovR protein to carry on signal transduction. Electromobility shift
      assays (EMSA) and green fluorescent protein (GFP) reporter gene expression assays
      showed the specific binding of BovR to the bovA promoter, indicating that BovR
      regulates bovA expression by direct binding between them. Taken together, bovicin
      HJ50 biosynthesis is induced by bovicin HJ50 itself and regulated via the two
      component signal transduction system BovK-BovR.

PMID- 21075874
TI  - Recombination shapes the structure of an environmental Vibrio cholerae
      population.
AB  - Vibrio cholerae consists of pathogenic strains that cause sporadic
      gastrointestinal illness or epidemic cholera disease and nonpathogenic strains
      that grow and persist in coastal aquatic ecosystems. Previous studies of disease
      causing strains have shown V. cholerae to be a primarily clonal bacterial
      species, but isolates analyzed have been strongly biased toward pathogenic
      genotypes, while representing only a small sample of the vast diversity in
      environmental strains. In this study, we characterized homologous recombination
      and structure among 152 environmental V. cholerae isolates and 13 other putative
      Vibrio isolates from coastal waters and sediments in central California, as well
      as four clinical V. cholerae isolates, using multilocus sequence analysis of
      seven housekeeping genes. Recombinant regions were identified by at least three
      detection methods in 72% of our V. cholerae isolates. Despite frequent
      recombination, significant linkage disequilibrium was still detected among the V.
      cholerae sequence types. Incongruent but nonrandom associations were observed for
      maximum likelihood topologies from the individual loci. Overall, our estimated
      recombination rate in V. cholerae of 6.5 times the mutation rate is similar to
      those of other sexual bacteria and appears frequently enough to restrict
      selection from purging much of the neutral intraspecies diversity. These data
      suggest that frequent recombination among V. cholerae may hinder the
      identification of ecotypes in this bacterioplankton population.

PMID- 21075879
TI  - Dynamic analysis of the Lactococcus lactis transcriptome in cheeses made from
      milk concentrated by ultrafiltration reveals multiple strategies of adaptation to
      stresses.
AB  - Lactococcus lactis is used extensively for the production of various cheeses. At
      every stage of cheese fabrication, L. lactis has to face several stress
      generating conditions that result from its own modification of the environment as
      well as externally imposed conditions. We present here the first in situ global
      gene expression profile of L. lactis in cheeses made from milk concentrated by
      ultrafiltration (UF-cheeses), a key economical cheese model. The transcriptomic
      response of L. lactis was analyzed directly in a cheese matrix, starting from as
      early as 2 h and continuing for 7 days. The growth of L. lactis stopped after 24
      h, but metabolic activity was maintained for 7 days. Conservation of its
      viability relied on an efficient proteolytic activity measured by an increasing,
      quantified number of free amino acids in the absence of cell lysis. Extensive
      downregulation of genes under CodY repression was found at day 7. L. lactis
      developed multiple strategies of adaptation to stressful modifications of the
      cheese matrix. In particular, expression of genes involved in acidic- and
      oxidative-stress responses was induced. L. lactis underwent unexpected carbon
      limitation characterized by an upregulation of genes involved in carbon
      starvation, principally due to the release of the CcpA control. We report for the
      first time that in spite of only moderately stressful conditions, lactococci
      phage is repressed under UF-cheese conditions.

PMID- 21075880
TI  - Diversity of phytoplankton nitrate transporter sequences from isolated single
      cells and mixed samples from the East China Sea and mRNA quantification.
AB  - The transcript abundances of nitrate transporter genes (Nrt2) were proposed as
      potential markers for nitrogen deficiency in marine diatoms. To correctly
      quantify diatom Nrt2 mRNA in the East China Sea (ECS), we utilized both mixed
      species sequencing and single-cell PCR to expand the sequence database for this
      region. Using the single-cell method of PCR, 9 new diatom Nrt2 sequences
      belonging to 5 genera, the Nrt2 sequences of which have never been reported
      before, were obtained. On the other hand, 291 sequences homologous to Nrt2 were
      retrieved from mixed-species sequencing using degenerate primers, and these
      sequences were clustered into 12 major groups according to a phylogenetic
      analysis. Based on sequence alignments, 11 pairs of group-specific PCR primers
      were designed to detect Nrt2 mRNA levels in the ECS, and 3 of these primer pairs
      showed high specificity to target species. In ECS phytoplankton samples,
      environmental RNA was amplified via antisense RNA amplification followed by cDNA
      production. Subsequently, Nrt2 transcript levels were readily detected using
      quantitative PCR. Our results indicated that investigating sequence diversity
      followed by careful primer design and evaluation is a good strategy to quantify
      the expression of genes of ecologically important phytoplankton.

PMID- 21075881
TI  - Transformation of, and heterologous protein expression in, Lactobacillus agilis
      and Lactobacillus vaginalis isolates from the chicken gastrointestinal tract.
AB  - Lactobacilli are naturally found in the gastrointestinal tract of chickens, and
      there is interest in utilizing autochthonous strains for the delivery of
      therapeutic proteins. Previously we identified three chicken-derived
      Lactobacillus strains, Lactobacillus agilis La3, Lactobacillus vaginalis Lv5, and
      Lactobacillus crispatus Lc9, which persist in the gastrointestinal tract of
      chickens fed either a commercial or high-protein diet. In the current study, we
      investigated the ability to electrotransform these strains, determined plasmid
      vector stability, and compared reporter gene expression directed by several
      different promoters. The La3 and Lv5 strains were reproducibly transformed with
      efficiencies of 10(8) and 10(6) transformants per microgram of plasmid DNA,
      respectively. The third strain tested, L. crispatus Lc9, was recalcitrant to all
      transformation protocols examined. The plasmid vectors pTRK563 and pTRKH2 were
      maintained over 100 generations in La3 and Lv5, respectively. The ability of La3
      and Lv5 to express the heterologous reporter gene gfp was analyzed using
      heterologous and homologous promoters. Transformants of both La3 and Lv5
      containing the La3 ldhL promoter were the most fluorescent. To our knowledge,
      this is the first report of successful transformation and heterologous protein
      expression in L. agilis and L. vaginalis. The ability of these strains to express
      heterologous proteins in vitro indicates their potential utility as in vivo
      delivery vectors for therapeutic peptides to the chicken gastrointestinal tract.

PMID- 21075882
TI  - Isolation of oligotrophic denitrifiers carrying previously uncharacterized
      functional gene sequences.
AB  - Oligotrophic denitrifying bacteria, including those belonging to the genera
      Herbaspirillum, Azospirillum, and Bradyrhizobium, were obtained using a single
      cell isolation technique. The taxonomic composition of the denitrifier population
      was similar to those assessed by previous culture-independent studies. The
      sequencing of nitrite reductase and N(2)O reductase genes of these strains
      revealed previously unknown links between 16S rRNA and the denitrification
      functional gene phylogenies. In particular, we identified Bradyrhizobium strains
      that harbor nirS sequences previously detected only in culture-independent
      studies.

PMID- 21075883
TI  - Randomized soil survey of the distribution of Burkholderia pseudomallei in rice
      fields in Laos.
AB  - Melioidosis is a major cause of morbidity and mortality in Southeast Asia, where
      the causative organism (Burkholderia pseudomallei) is present in the soil. In the
      Lao People's Democratic Republic (Laos), B. pseudomallei is a significant cause
      of sepsis around the capital, Vientiane, and has been isolated in soil near the
      city, adjacent to the Mekong River. We explored whether B. pseudomallei occurs in
      Lao soil distant from the Mekong River, drawing three axes across northwest,
      northeast, and southern Laos to create nine sampling areas in six provinces.
      Within each sampling area, a random rice field site containing a grid of 100
      sampling points each 5 m apart was selected. Soil was obtained from a depth of 30
      cm and cultured for B. pseudomallei. Four of nine sites (44%) were positive for
      B. pseudomallei, including all three sites in Saravane Province, southern Laos.
      The highest isolation frequency was in east Saravane, where 94% of soil samples
      were B. pseudomallei positive with a geometric mean concentration of 464 CFU/g
      soil (95% confidence interval, 372 to 579 CFU/g soil; range, 25 to 10,850 CFU/g
      soil). At one site in northwest Laos (Luangnamtha), only one sample (1%) was
      positive for B. pseudomallei, at a concentration of 80 CFU/g soil. Therefore, B.
      pseudomallei occurs in Lao soils beyond the immediate vicinity of the Mekong
      River, alerting physicians to the likelihood of melioidosis in these areas.
      Further studies are needed to investigate potential climatic, soil, and
      biological determinants of this heterogeneity.

PMID- 21075884
TI  - Commensal effect of pectate lyases secreted from Dickeya dadantii on
      proliferation of Escherichia coli O157:H7 EDL933 on lettuce leaves.
AB  - The outbreaks caused by enterohemorrhagic Escherichia coli O157:H7 on leafy
      greens have raised serious and immediate food safety concerns. It has been
      suggested that several phytopathogens aid in the persistence and proliferation of
      the human enteropathogens in the phyllosphere. In this work, we examined the
      influence of virulence mechanisms of Dickeya dadantii 3937, a broad-host-range
      phytopathogen, on the proliferation of the human pathogen E. coli O157:H7 EDL933
      (EDL933) on postharvest lettuce by coinoculation of EDL933 with D. dadantii 3937
      derivatives that have mutations in virulence-related genes. A type II secretion
      system (T2SS)-deficient mutant of D. dadantii 3937, A1919 (DeltaoutC), lost the
      capability to promote the multiplication of EDL933, whereas Ech159 (DeltarpoS), a
      stress-responsive sigma factor RpoS-deficient mutant, increased EDL933
      proliferation on lettuce leaves. A spectrophotometric enzyme activity assay
      revealed that A1919 (DeltaoutC) was completely deficient in the secretion of
      pectate lyases (Pels), which play a major role in plant tissue maceration. In
      contrast to A1919 (DeltaoutC), Ech159 (DeltarpoS) showed more than 2-fold-greater
      Pel activity than the wild-type D. dadantii 3937. Increased expression of pelD
      (encodes an endo-pectate lyase) was observed in Ech159 (DeltarpoS) in planta.
      These results suggest that the pectinolytic activity of D. dadantii 3937 is the
      dominant determinant of enhanced EDL933 proliferation on the lettuce leaves. In
      addition, RpoS, the general stress response sigma factor involved in cell
      survival in suboptimal conditions, plays a role in EDL933 proliferation by
      controlling the production of pectate lyases in D. dadantii 3937.

PMID- 21075885
TI  - Tangential-flow ultrafiltration with integrated inhibition detection for recovery
      of surrogates and human pathogens from large-volume source water and finished
      drinking water.
AB  - Tangential-flow ultrafiltration was optimized for the recovery of Escherichia
      coli, Enterococcus faecalis, Clostridium perfringens spores, bacteriophages MS2
      and PRD1, murine norovirus, and poliovirus seeded into 100-liter surface water
      (SW) and drinking water (DW) samples. SW and DW collected from two drinking water
      treatment plants were then evaluated for human enteric viruses.

PMID- 21075886
TI  - Influence of external resistance on electrogenesis, methanogenesis, and anode
      prokaryotic communities in microbial fuel cells.
AB  - The external resistance (R(ext)) of microbial fuel cells (MFCs) regulates both
      the anode availability as an electron acceptor and the electron flux through the
      circuit. We evaluated the effects of R(ext) on MFCs using acetate or glucose. The
      average current densities (I) ranged from 40.5 mA/m(2) (9,800 Omega) to 284.5
      mA/m(2) (150 Omega) for acetate-fed MFCs (acetate-fed reactors [ARs]), with a
      corresponding anode potential (E(an)) range of -188 to -4 mV (versus a standard
      hydrogen electrode [SHE]). For glucose-fed MFCs (glucose-fed reactors [GRs]), I
      ranged from 40.0 mA/m(2) (9,800 Omega) to 273.0 mA/m(2) (150 Omega), with a
      corresponding E(an) range of -189 to -7 mV. ARs produced higher Coulombic
      efficiencies and energy efficiencies than GRs over all tested R(ext) levels
      because of electron and potential losses from glucose fermentation. Biogas
      production accounted for 14 to 18% of electron flux in GRs but only 0 to 6% of
      that in ARs. GRs produced similar levels of methane, regardless of the R(ext).
      However, total methane production in ARs increased as R(ext) increased,
      suggesting that E(an) might influence the competition for substrates between
      exoelectrogens and methanogens in ARs. An increase of R(ext) to 9,800 Omega
      significantly changed the anode bacterial communities for both ARs and GRs, while
      operating at 970 Omega and 150 Omega had little effect. Deltaproteobacteria and
      Bacteroidetes were the major groups found in anode communities in ARs and GRs.
      Betaproteobacteria and Gammaproteobacteria were found only in ARs. Bacilli were
      abundant only in GRs. The anode-methanogenic communities were dominated by
      Methanosaetaceae, with significantly lower numbers of Methanomicrobiales. These
      results show that R(ext) affects not only the E(an) and current generation but
      also the anode biofilm community and methanogenesis.

PMID- 21075887
TI  - Respiration response imaging for real-time detection of microbial function at the
      single-cell level.
AB  - The ability to detect specific functions of uncultured microbial cells in complex
      natural communities remains one of the most difficult tasks of environmental
      microbiology. Here we present respiration response imaging (RRI) as a novel
      fluorescence microscopy-based approach for the identification of microbial
      function, such as the ability to use C(1) substrates, at a single-cell level. We
      demonstrate that RRI could be used for the investigation of heterogeneity of a
      single microbial population or for functional profiling of microbial cells from
      complex environmental communities, such as freshwater lake sediment.

PMID- 21075888
TI  - Transformation system for Hypocrea jecorina (Trichoderma reesei) that favors
      homologous integration and employs reusable bidirectionally selectable markers.
AB  - Hypocrea jecorina is an industrially important filamentous fungus due to its
      effective production of hydrolytic enzymes. It has received increasing interest
      because of its ability to convert lignocellulosic biomass to monomeric sugars,
      which can be converted into biofuels or platform chemicals. Genetic engineering
      of strains is a highly important means of meeting the requirements of tailor-made
      applications. Therefore, we report the development of a transformation system
      that allows highly efficient gene targeting by using a tmus53 (human LIG4
      homolog) deletion strain. Moreover, it permits the unlimited reuse of the same
      marker by employing a Cre/loxP-based excision system. Both marker insertion and
      marker excision can be positively selected for by combining resistance to
      hygromycin B and loss of sensitivity to fluoroacetamide. Finally, the marker
      pyr4, also positively selectable for insertion and loss, can be used to remove
      the cre gene.

PMID- 21075889
TI  - Relative and absolute quantitative real-time PCR-based quantifications of hcnC
      and phlD gene transcripts in natural soil spiked with Pseudomonas sp. strain
      LBUM300.
AB  - Transcriptional analysis of microbial gene expression using relative quantitative
      real-time PCR (qRT-PCR) has been hampered by various technical problems. One such
      problem is the unavailability of an exogenous standard robust enough for use in a
      complex matrix like soil. To circumvent this technical issue, we made use of a
      recently developed artificial RNA (myIC) as an exogenous "spike-in" control.
      Nonsterile field soil was inoculated with various concentrations of the test
      bacterium Pseudomonas sp. strain LBUM300, ranging from 4.3- to 8.3-log bacterial
      cells per gram of soil. Total soil RNA was extracted at days 0, 7, and 14
      postinoculation, and using two-step TaqMan assays, phlD (encoding the production
      of 2,4-diacetylphloroglucinol) and hcnC (encoding the production of hydrogen
      cyanide) gene expression was monitored. For relative quantification, a defined
      quantity of in vitro-synthesized myIC RNA was spiked during the RNA extraction
      procedure. Absolute qRT-PCR was also performed in parallel. Both the absolute and
      relative quantifications showed similar transcriptional trends. Overall, the
      transcriptional activity of phlD and hcnC changed over time and with respect to
      the bacterial concentrations used. Transcripts of the phlD and hcnC genes were
      detected for all five bacterial concentrations, but the phlD transcript copy
      numbers detected were lower than those detected for hcnC, regardless of the
      initial bacterial concentration or sampling date. For quantifying a low number of
      transcripts, the relative method was more reliable than the absolute method. This
      study demonstrates for the first time the use of a relative quantification
      approach to quantifying microbial gene transcripts from field soil using an
      exogenous spike-in control.

PMID- 21075890
TI  - Different contributions of HtrA protease and chaperone activities to
      Campylobacter jejuni stress tolerance and physiology.
AB  - The microaerophilic bacterium Campylobacter jejuni is the most common cause of
      bacterial food-borne infections in the developed world. Tolerance to
      environmental stress relies on proteases and chaperones in the cell envelope,
      such as HtrA and SurA. HtrA displays both chaperone and protease activities, but
      little is known about how each of these activities contributes to stress
      tolerance in bacteria. In vitro experiments showed temperature-dependent protease
      and chaperone activities of C. jejuni HtrA. A C. jejuni mutant lacking only the
      protease activity of HtrA was used to show that the HtrA chaperone activity is
      sufficient for growth at high temperature or under oxidative stress, whereas the
      HtrA protease activity is essential only under conditions close to the growth
      limit for C. jejuni. However, the protease activity was required to prevent
      induction of the cytoplasmic heat shock response even under optimal growth
      conditions. Interestingly, the requirement of HtrA at high temperatures was found
      to depend on the oxygen level, and our data suggest that HtrA may protect
      oxidatively damaged proteins. Finally, protease activity stimulates HtrA
      production and oligomer formation, suggesting that a regulatory role depends on
      the protease activity of HtrA. Studying a microaerophilic organism encoding only
      two known periplasmic chaperones (HtrA and SurA) revealed an efficient HtrA
      chaperone activity and proposed multiple roles of the protease activity,
      increasing our understanding of HtrA in bacterial physiology.

PMID- 21075891
TI  - Microbial community fingerprinting by differential display-denaturing gradient
      gel electrophoresis.
AB  - Complex microbial communities exhibit a large diversity, hampering
      differentiation by DNA fingerprinting. Herein, differential display-denaturing
      gradient gel electrophoresis is proposed. By adding a nucleotide to the 3' ends
      of PCR primers, 16 primer pairs and fingerprints were generated per community.
      Complexity reduction in each partial fingerprint facilitates sample comparison.

PMID- 21075892
TI  - Domain organization and evolution of multifunctional autoprocessing repeats-in
      toxin (MARTX) toxin in Vibrio vulnificus.
AB  - The objective of this study was to analyze multifunctional autoprocessing repeats
      in-toxin (MARTX) toxin domain organization within the aquatic species Vibrio
      vulnificus as well as to study the evolution of the rtxA1 gene. The species is
      subdivided into three biotypes that differ in host range and geographical
      distribution. We have found three different types (I, II, and III) of V.
      vulnificus MARTX (MARTX(Vv)) toxins with common domains (an autocatalytic
      cysteine protease domain [CPD], an alpha/beta-hydrolase domain, and a domain
      resembling that of the LifA protein of Escherichia coli O127:H6 E2348/69
      [Efa/LifA]) and specific domains (a Rho-GTPase inactivation domain [RID], a
      domain of unknown function [DUF], a domain resembling that of the rtxA protein of
      Photorhabdus asymbiotica [rtxA(PA)], and an actin cross-linking domain [ACD]).
      Biotype 1 isolates harbor MARTX(Vv) toxin types I and II, biotype 2 isolates
      carry MARTX(Vv) toxin type III, and biotype 3 isolates have MARTX(Vv) toxin type
      II. The analyzed biotype 2 isolates harbor two identical copies of rtxA1, one
      chromosomal and the other plasmidic. The evolutionary history of the gene
      demonstrates that MARTX(Vv) toxins are mosaics, comprising pieces with different
      evolutionary histories, some of which have been acquired by intra- or
      interspecific horizontal gene transfer. Finally, we have found evidence that the
      evolutionary history of the rtxA1 gene for biotype 2 differs totally from the
      gene history of biotypes 1 and 3.

PMID- 21075893
TI  - Differential protein expression in Streptococcus uberis under planktonic and
      biofilm growth conditions.
AB  - The bovine pathogen Streptococcus uberis was assessed for biofilm growth. The
      transition from planktonic to biofilm growth in strain 0140J correlated with an
      upregulation of several gene products that have been shown to be important for
      pathogenesis, including a glutamine ABC transporter (SUB1152) and a lactoferrin
      binding protein (gene lbp; protein SUB0145).

PMID- 21075894
TI  - Engineered biosynthesis of gilvocarcin analogues with altered deoxyhexopyranose
      moieties.
AB  - A combinatorial biosynthetic approach was used to interrogate the donor substrate
      flexibility of GilGT, the glycosyltransferase involved in C-glycosylation during
      gilvocarcin biosynthesis. Complementation of gilvocarcin mutant Streptomyces
      lividans TK24 (cosG9B3-U(-)), in which the biosynthesis of the natural sugar
      donor substrate was compromised, with various deoxysugar plasmids led to the
      generation of six gilvocarcin analogues with altered saccharide moieties.
      Characterization of the isolated gilvocarcin derivatives revealed five new
      compounds, including 4-beta-C-D-olivosyl-gilvocarcin V (D-olivosyl GV), 4-beta-C
      D-olivosyl-gilvocarcin M (D-olivosyl GM), 4-beta-C-D-olivosyl-gilvocarcin E (D
      olivosyl GE), 4-alpha-C-L-rhamnosyl-gilvocarcin M (polycarcin M), 4-alpha-C-L
      rhamnosyl-gilvocarcin E (polycarcin E), and the recently characterized 4-alpha-C
      L-rhamnosyl-gilvocarcin V (polycarcin V). Preliminary anticancer assays showed
      that D-olivosyl-gilvocarcin and polycarcin V exhibit antitumor activities
      comparable to that of their parent drug congener, gilvocarcin V, against human
      lung cancer (H460), murine lung cancer (LL/2), and breast cancer (MCF-7) cell
      lines. Our findings demonstrate GilGT to be a moderately flexible C
      glycosyltransferase able to transfer both D- and L-hexopyranose moieties to the
      unique angucyclinone-derived benzo[D]naphtho[1,2b]pyran-6-one backbone of the
      gilvocarcins.

PMID- 21075895
TI  - Real-time PCR assay to differentiate Listeriolysin S-positive and -negative
      strains of Listeria monocytogenes.
AB  - Due to the severity of the food-borne infection listeriosis, strict legislation
      governs the detectable and permissible limits at which Listeria monocytogenes is
      permitted in foods. These requirements, coupled with the ubiquitous nature of L.
      monocytogenes strains and the potential for epidemic outbreaks, mean that the
      pathogen can devastate affected sectors of the food industry. Although almost all
      L. monocytogenes strains have the potential to cause listeriosis, those
      implicated in the vast majority of epidemics belong to a subset of strains
      belonging to evolutionary lineage I. It has been established that a significant
      proportion of these strains, including those implicated in the majority of
      outbreaks, produce an additional hemolysin, designated listeriolysin S (LLS),
      which may be responsible for the enhanced virulence of these strains. In order to
      ultimately establish this definitively, it is important to first be able to
      rapidly discriminate between LLS-positive and -negative strains. Here, after
      essential genes within the LLS-encoding cluster, Listeria pathogenicity island 3,
      were identified by deletion mutagenesis, a real-time PCR assay which targets one
      such gene, llsX, was developed as a means of identifying LLS-positive L.
      monocytogenes. The specificity of the assay was validated against a panel of 40
      L. monocytogenes strains (20 of which were LLS positive) and 25 strains
      representative of other Listeria species. Furthermore, 1 CFU of an LLS-positive
      strain per 25 g/ml of spiked foods was detected in less than 30 h when the assay
      was coupled with culture enrichment. The detection limit of this assay was 10
      genome equivalents.

PMID- 21075896
TI  - Phylogeographical patterns among Mediterranean sepiolid squids and their Vibrio
      symbionts: environment drives specificity among sympatric species.
AB  - Bobtail squid from the genera Sepiola and Rondeletiola (Cephalopoda: Sepiolidae)
      form mutualistic associations with luminous Gram-negative bacteria
      (Gammaproteobacteria: Vibrionaceae) from the genera Vibrio and Photobacterium.
      Symbiotic bacteria proliferate inside a bilobed light organ until they are
      actively expelled by the host into the surrounding environment on a diel basis.
      This event results in a dynamic symbiont population with the potential to
      establish the symbiosis with newly hatched sterile (axenic) juvenile sepiolids.
      In this study, we examined the genetic diversity found in populations of
      sympatric sepiolid squid species and their symbionts by the use of nested clade
      analysis with multiple gene analyses. Variation found in the distribution of
      different species of symbiotic bacteria suggests a strong influence of abiotic
      factors in the local environment, affecting bacterial distribution among
      sympatric populations of hosts. These abiotic factors include temperature
      differences incurred by a shallow thermocline, as well as a lack of strong
      coastal water movement accompanied by seasonal temperature changes in overlapping
      niches. Host populations are stable and do not appear to have a significant role
      in the formation of symbiont populations relative to their distribution across
      the Mediterranean Sea. Additionally, all squid species examined (Sepiola affinis,
      S. robusta, S. ligulata, S. intermedia, and Rondeletiola minor) are genetically
      distinct from one another regardless of location and demonstrate very little
      intraspecific variation within species. These findings suggest that physical
      boundaries and distance in relation to population size, and not host specificity,
      are important factors in limiting or defining gene flow within sympatric marine
      squids and their associated bacterial symbionts in the Mediterranean Sea.

PMID- 21075898
TI  - Effects of ionic strength on bacteriophage MS2 behavior and their implications
      for the assessment of virus retention by ultrafiltration membranes.
AB  - Bacteriophage MS2 is widely used as a surrogate to estimate pathogenic virus
      elimination by membrane filtration processes used in water treatment. Given that
      this water technology may be conducted with different types of waters, we focused
      on investigating the effects of ionic strength on MS2 behavior. For this, MS2 was
      analyzed while suspended in solutions of various ionic strengths, first in a
      batch experiment and second during membrane ultrafiltration, and quantified using
      (i) quantitative reverse transcriptase PCR (qRT-PCR), which detects the total
      number of viral genomes, (ii) qRT-PCR without the RNA extraction step, which
      reflects only particles with a broken capsid (free RNA), and (iii) the PFU
      method, which detects only infectious viruses. At the beginning of the batch
      experiments using solutions containing small amounts of salts, losses of MS2
      infectivity (90%) and broken particles (20%) were observed; these proportions did
      not change during filtration. In contrast, in high-ionic-strength solutions,
      bacteriophage kept its biological activity under static conditions, but it
      quickly lost its infectivity during the filtration process. Increasing the ionic
      strength decreased both the inactivation and the capsid breakup in the feed
      suspension and increased the loss of infectivity in the filtration retentate,
      while the numbers of MS2 genomes were identical in both experiments. In
      conclusion, the effects of ionic strength on MS2 behavior may significantly
      distort the results of membrane filtration processes, and therefore, the
      combination of classical and molecular methods used here is useful for an
      effective validation of the retention efficiency of ultrafiltration membranes.

PMID- 21075899
TI  - Pyrosequencing of the genital microbiotas of HIV-seropositive and -seronegative
      women reveals Lactobacillus iners as the predominant Lactobacillus Species.
AB  - The species of vaginal lactobacilli in HIV-seropositive and -seronegative women
      were determined by 16S gene pyrosequencing. Lactobacillus iners sequences were
      the predominant lactobacillus sequences in 66% of HIV(+) women and 90% of HIV(-)
      women. This has implications for resistance of HIV(+) and HIV(-) women to genital
      colonization by pathogenic organisms.

PMID- 21075900
TI  - Timing in trace conditioning of the nictitating membrane response of the rabbit
      (Oryctolagus cuniculus): scalar, nonscalar, and adaptive features.
AB  - Using interstimulus intervals (ISIs) of 125, 250, and 500 msec in trace
      conditioning of the rabbit nictitating membrane response, the offset times and
      durations of conditioned responses (CRs) were collected along with onset and peak
      latencies. All measures were proportional to the ISI, but only onset and peak
      latencies conformed to the criterion for scalar timing. Regarding the CR's
      possible protective overlap of the unconditioned stimulus (US), CR duration
      increased with ISI, while the peak's alignment with the US declined. Implications
      for models of timing and CR adaptiveness are discussed.

PMID- 21075902
TI  - Aquimarina addita sp. nov., isolated from seawater.
AB  - An orange-coloured, rod-shaped, non-motile, Gram-reaction-negative, strictly
      aerobic bacterial strain, designated JC2680(T), was isolated from a seawater
      sample of Jeju Island, Korea. The isolate required sea salts for growth.
      Flexirubin-type pigments were absent. 16S rRNA gene sequence analysis indicated
      that the test strain belonged to the genus Aquimarina within the family
      Flavobacteriaceae, but shared relatively low levels of similarity (93.6-95.9 %)
      with the type strains of recognized Aquimarina species. The predominant cellular
      fatty acids [iso-C(17 : 0) 3-OH, iso-C(15 : 0) and summed feature 9 (comprising
      10-methyl C(16 : 0) and/or iso-C(17 : 1)omega9c) and DNA G+C content (35 mol%)
      were consistent with the assignment of strain JC2680(T) to the genus Aquimarina.
      However, a number of phenotypic characteristics, namely inability to grow under
      microaerophilic conditions, differences in enzyme reactions, and absence of
      flexirubin-type pigments and gliding motility, clearly distinguished strain
      JC2680(T) from recognized species of the genus Aquimarina. The data presented
      thus indicate that strain JC2680(T) represents a novel species of the genus
      Aquimarina, for which the name Aquimarina addita sp. nov. is proposed. The type
      strain is JC2680(T) ( = KACC 14156(T)  = JCM 17106(T)).

PMID- 21075903
TI  - Lactobacillus ozensis sp. nov., isolated from mountain flowers.
AB  - Five strains (Mizu2-1(T), Gon2-7, Koba6-1, Koyu2-2 and Miya2-2) of lactic acid
      bacteria (LAB) were isolated from flowers in Oze National Park, Japan, using
      anaerobic cultivation. The five isolates were found to share identical 16S rRNA
      gene sequences. The isolates exhibited low levels of 16S rRNA gene sequence
      similarity to known LAB; the closest recognized relatives of strain Mizu2-1(T)
      were the type strains of Lactobacillus kunkeei (94.9 %), Lactobacillus kefiri
      (94.1 %) and Lactobacillus buchneri (93.9 %). Comparative analyses of rpoA and
      pheS gene sequences demonstrated that the novel isolates did not show significant
      relationships to other Lactobacillus species. The strains were Gram-stain
      positive, catalase-negative and heterofermentative. Anaerobic growth was better
      than aerobic growth. The isolates utilized a narrow range of carbohydrates as
      sources of carbon and energy, including glucose and fructose. On the basis of
      phenotypic characteristics and phylogenetic data, the isolates represent a novel
      species of the genus Lactobacillus, for which the name Lactobacillus ozensis sp.
      nov. is proposed. The type strain is Mizu2-1(T) ( = JCM 17196(T)  = DSM
      23829(T)).

PMID- 21075901
TI  - Human lung immunity against Mycobacterium tuberculosis: insights into
      pathogenesis and protection.
AB  - The study of human pulmonary immunity against Mycobacterium tuberculosis (M.tb)
      provides a unique window into the biological interactions between the human host
      and M.tb within the broncho-alveolar microenvironment, the site of natural
      infection. Studies of bronchoalveolar cells (BACs) and lung tissue evaluate
      innate, adaptive, and regulatory immune mechanisms that collectively contribute
      to immunological protection or its failure. In aerogenically M.tb-exposed healthy
      persons lung immune responses reflect early host pathogen interactions that may
      contribute to sterilization, the development of latent M.tb infection, or
      progression to active disease. Studies in these persons may allow the
      identification of biomarkers of protective immunity before the initiation of
      inflammatory and disease-associated immunopathological changes. In healthy close
      contacts of patients with tuberculosis (TB) and during active pulmonary TB,
      immune responses are compartmentalized to the lungs and characterized by an
      exuberant helper T-cell type 1 response, which as suggested by recent evidence is
      counteracted by local suppressive immune mechanisms. Here we discuss how
      exploring human lung immunity may provide insights into disease progression and
      mechanisms of failure of immunological protection at the site of the initial host
      pathogen interaction. These findings may also aid in the identification of new
      biomarkers of protective immunity that are urgently needed for the development of
      new and the improvement of current TB vaccines, adjuvant immunotherapies, and
      diagnostic technologies. To facilitate further work in this area, methodological
      and procedural approaches for bronchoalveolar lavage studies and their
      limitations are also discussed.

PMID- 21075897
TI  - Environmental patterns are imposed on the population structure of Escherichia
      coli after fecal deposition.
AB  - The intestinal microbe Escherichia coli is subject to fecal deposition in
      secondary habitats, where it persists transiently, allowing for the opportunity
      to colonize new hosts. Selection in the secondary habitat can be postulated, but
      its impact on the genomic diversity of E. coli is unknown. Environmental
      selective pressure on extrahost E. coli can be revealed by landscape genetic
      analysis, which examines the influences of dispersal processes, landscape
      features, and the environment on the spatiotemporal distribution of genes in
      natural populations. We conducted multilocus sequence analysis of 353 E. coli
      isolates from soil and fecal samples obtained in a recreational meadow to examine
      the ecological processes controlling their distributions. Soil isolates, as a
      group, were not genetically distinct from fecal isolates, with only 0.8% of
      genetic variation and no fixed mutations attributed to the isolate source.
      Analysis of the landscape genetic structure of E. coli populations showed a
      patchy spatial structure consistent with patterns of fecal deposition.
      Controlling for the spatial pattern made it possible to detect environmental
      gradients of pH, moisture, and organic matter corresponding to the genetic
      structure of E. coli in soil. Ecological distinctions among E. coli
      subpopulations (i.e., E. coli reference collection [ECOR] groups) contributed to
      variation in subpopulation distributions. Therefore, while fecal deposition is
      the major predictor of E. coli distributions on the field scale, selection
      imposed by the soil environment has a significant impact on E. coli population
      structure and potentially amplifies the occasional introduction of stress
      tolerant strains to new host individuals by transmission through water or food.

PMID- 21075904
TI  - Corynebacterium nuruki sp. nov., isolated from an alcohol fermentation starter.
AB  - A novel Gram-positive, strictly aerobic and non-motile bacterial strain, S6-4(T),
      was isolated from a Korean alcohol fermentation starter. Optimal growth occurred
      at 37  degrees C, at pH 8 and in 1 % (w/v) NaCl. The isolate was positive for
      oxidase and catalase. It assimilated various sugars and acids were produced from
      several carbohydrates. The major cell-wall sugars were galactose and arabinose.
      The major fatty acids of strain S6-4(T) were C(16 : 0), C(17 : 1)omega9c, C(18 :
      1)omega9c and 10-methyl C(18 : 0) (tuberculostearic acid). The predominant
      isoprenoid quinone was menaquinone MK-9(H(2)) and peptidoglycan amino acids were
      meso-diaminopimelic acid, alanine, glycine and glutamic acid. The strain
      contained mycolic acids. According to phylogenetic analysis based on 16S rRNA
      gene sequences, strain S6-4(T) was most closely related to Corynebacterium
      variabile DSM 20132(T) (98.1 % similarity). The genomic DNA G+C content of strain
      S6-4(T) was 73.6 mol% and DNA-DNA hybridization values with related strains were
      below 33+/-4 %. On the basis of phenotypic, genotypic and phylogenetic data,
      strain S6-4(T) represents a novel species in the genus Corynebacterium, for which
      the name Corynebacterium nuruki sp. nov. is proposed; the type strain is S6-4(T)
      ( = KACC 15032(T)  = JCM 17162(T)).

PMID- 21075905
TI  - Hoeflea anabaenae sp. nov., an epiphytic symbiont that attaches to the
      heterocysts of a strain of Anabaena.
AB  - The heterotrophic, epiphytic, symbiotic bacterial strain WH2K(T) was previously
      isolated from a two-member culture in which it was attached to the heterocysts of
      a strain of Anabaena (SSM-00). Analysis of its 16S rRNA gene sequence
      demonstrated that the symbiont was most closely related to the type strain of
      Hoeflea marina (96.9 % similarity), which belongs to the family
      Phyllobacteriaceae within the order Rhizobiales of the class Alphaproteobacteria.
      A polyphasic taxonomic study was performed on strain WH2K(T), which consisted of
      irregular rods (2-5 um long, 0.2 um wide) that appeared to be narrower at one
      pole. Optimal growth was obtained in complex media with 15 g sea salts l(-1), at
      18-34  degrees C (30  degrees C optimum) and at pH 6.0-8.0 (optimum pH 6.5).
      Unknown growth requirements were provided by small amounts of yeast extract but
      not by standard vitamin and trace metal solutions. Of the substrates tested,
      WH2K(T) was able to utilize only acetate, pyruvate, malate and fumarate. Growth
      was observed only under aerobic and microaerobic conditions, and nitrate was not
      reduced. No photosynthetic pigments were detected under any of the growth
      conditions tested. The predominant fatty acids were a summed feature that
      comprises C(18 : 1)omega7c, C(18 : 1)omega9t, C(18 : 1)omega12t or any
      combination of these (64.0 %) and an unidentified fatty acid of equivalent chain
      length 17.603 (13.5 %). The polar lipid profile consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphoglycolipid,
      unknown lipids and an unidentified aminolipid. The only respiratory ubiquinone
      detected was Q-10. The DNA G+C content of the strain was 58.1 mol%. The organism
      can form a site-specific attached symbiotic relationship with a species of
      Anabaena. Based on phylogenetic and phenotypic evidence, it is proposed that
      strain WH2K(T) be classified within a novel species of the genus Hoeflea, for
      which the name Hoeflea anabaenae sp. nov. is proposed. The type strain is WH2K(T)
      ( = CCUG 56626(T)  = NRRL B-59520(T)).

PMID- 21075906
TI  - Thioprofundum hispidum sp. nov., an obligately chemolithoautotrophic sulfur
      oxidizing gammaproteobacterium isolated from the hydrothermal field on Suiyo
      Seamount, and proposal of Thioalkalispiraceae fam. nov. in the order
      Chromatiales.
AB  - A novel mesophilic, facultatively anaerobic, sulfur-oxidizing bacterial strain,
      designated gps61(T), was isolated from a surface rock sample collected from the
      hydrothermal field of Suiyo Seamount on the Izu-Bonin Arc in the Western Pacific
      Ocean. Cells of the isolate were rod-shaped with a single sheathed polar
      flagellum. Neither extensive internal membranes nor storage materials were
      present in the cells. In a 20 % CO(2) atmosphere, strain gps61(T) grew using
      thiosulfate, sulfur or tetrathionate as electron donors and oxygen or nitrate as
      electron acceptors. Other substrates, including organic acids and sugars, did not
      support growth, indicating that strain gps61(T) was an obligate
      chemolithoautotroph. 16S rRNA gene sequence analysis revealed that strain
      gps61(T) was closely related to Thioprofundum lithotrophicum 106(T) (98.5 %
      sequence similarity) in the order Chromatiales. Phylogenetic trees grouped strain
      gps61(T) and Thioprofundum lithotrophicum in the same cluster along with
      Thioalkalispira microaerophila and Thiohalophilus thiocyanoxidans, but it was
      apparent from the analysis that the novel strain had definitely departed from the
      family lineage. On the basis of its phylogenetic position along with its
      morphological and physiological characteristics, strain gps61(T) ( = NBRC
      101261(T)  = DSM 18546(T)) represents a novel species of the genus Thioprofundum,
      for which the name Thioprofundum hispidum sp. nov. is proposed. In addition, we
      propose a novel family name, Thioalkalispiraceae, in the order Chromatiales, to
      accommodate the genera Thioalkalispira, Thiohalophilus and Thioprofundum.

PMID- 21075907
TI  - Rhizobium pseudoryzae sp. nov., isolated from the rhizosphere of rice.
AB  - A Gram-stain-negative, aerobic, rod-shaped bacterium, designated strain J3
      A127(T), was isolated from the roots of fresh rice plants (Oryza sativa). Cells
      were non-motile and no flagellum was detected. Comparison of 16S rRNA gene
      sequences indicated that the strain was phylogenetically related to species of
      the genus Rhizobium, with closest similarity to Rhizobium oryzae Alt 505(T) (96.4
      %). The low levels of 16S rRNA gene sequence similarity (<90 %) found between the
      gyrB, atpD, recA and glnII gene sequences of strain J3-A127(T) and the type
      strains of recognized species of the genus Rhizobium also indicated that it
      represented a separate species. The temperature range for growth was 10-40 
      degrees C (optimum around 28  degrees C) and the pH range was 6.0-11.0 (optimum
      pH 7.0-8.0). Strain J3-A127(T) tolerated NaCl concentrations up to 5.0 % (w/v).
      The strain was catalase- and oxidase-positive. The main cellular fatty acids were
      summed feature 8 (C(18 : 1)omega7c and/or C(18 : 1)omega6; 46.7 %). The DNA G+C
      content of strain J3-A127(T) was 59.5 mol%. Strain J3-A127(T) did not form any
      nodules on four different legumes and the nodD and nifH genes were not detected
      by PCR. According to physiological and biochemical characteristics and genotypic
      data, strain J3-A127(T) is considered to represent a novel species of the genus
      Rhizobium, for which the name Rhizobium pseudoryzae sp. nov. is proposed. The
      type strain is J3-A127(T) ( = ACCC 10380(T) = KCTC 23294(T)).

PMID- 21075908
TI  - Calidifontibacter indicus gen. nov., sp. nov., a member of the family
      Dermacoccaceae isolated from a hot spring, and emended description of the family
      Dermacoccaceae.
AB  - During the course of a study on the bacterial diversity in Western Ghats, India,
      an actinobacterial strain, designated PC IW02(T), was isolated and characterized
      by a polyphasic taxonomic approach. Strain PC IW02(T) was a non-motile, Gram
      positive, short rod that formed creamish white to yellow coloured colonies. 16S
      rRNA gene sequence analysis showed that the novel strain showed highest sequence
      similarity with type strains of members of the genus Dermacoccus: Dermacoccus
      barathri (96.6 %), Dermacoccus profundi (96.5 %), Dermacoccus abyssi (96.4 %) and
      Dermacoccus nishinomiyaensis (95.9 %). The phylogenetic tree suggested that
      strain PC IW02(T) could represent a member of a new genus of the family
      Dermacoccaceae with the genus Demetria as closest clade. Pairwise sequence
      alignment with Demetria terragena HKI 0089(T) and Kytococcus sedentarius DSM
      20547(T) showed similarities of 94.2 and 93.7 %, respectively. Strain PC IW02(T)
      had MK-8(H(4)) as the major menaquinone. The major fatty acids were iso-C(16 : 0)
      (43.4 %), iso-C(16 : 1) H (17.2 %) and anteiso-C(17 : 0) (9.9 %). The diagnostic
      cell-wall amino acid at position 3 of the peptide subunit was lysine; the
      interpeptide bridge consisted of Gly-Ser-Asp. The polar lipids present were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides and phosphatidylserine, along with two unknown
      phospholipids. The genomic DNA G+C content of the isolate was 77 mol%. On the
      basis of phenotypic characteristics, including chemotaxonomic data, and 16S rRNA
      gene sequence similarities, strain PC IW02(T) represents a novel species in a new
      genus of the family Dermacoccaceae for which the name Calidifontibacter indicus
      gen. nov., sp. nov. is proposed. The type strain of Calidifontibacter indicus is
      PC IW02(T) ( = MTCC 8338(T) = DSM 22967(T) = JCM 16038(T)). An emended
      description of the family Dermacoccaceae is provided.

PMID- 21075909
TI  - Vibrio atlanticus sp. nov. and Vibrio artabrorum sp. nov., isolated from the
      clams Ruditapes philippinarum and Ruditapes decussatus.
AB  - Facultatively anaerobic marine bacteria isolated from cultured clams, Ruditapes
      decussatus and Ruditapes philippinarum, were previously investigated using
      amplified fragment length polymorphism (AFLP) and 16S rRNA gene sequence
      analyses. The isolates formed two AFLP clusters and belonged to the genus Vibrio,
      more precisely to the Splendidus clade. In this study, phylogenetic analyses
      based on sequences of the housekeeping genes rpoA, rpoD, pyrH, atpA and recA
      supported their inclusion in that clade forming two well differentiated groups
      with respect to the rest of the species within the clade, and confirmed that they
      formed two groups, separated from the rest of the species of the clade. DNA-DNA
      hybridization demonstrated that the isolates constitute two novel species of the
      genus Vibrio, which can be phenotypically differentiated from their closest
      relatives. The names Vibrio atlanticus sp. nov. and Vibrio artabrorum sp. nov.
      are proposed, with Vb 11.11(T) ( = CECT 7223(T)  = LMG 24300(T)) and Vb 11.8(T) (
      = CECT 7226(T)  = LMG 23865(T)) as the type strains, respectively.

PMID- 21075911
TI  - Pain as a Symptom in Patients Living With HIV/AIDS Seen at the Outpatient Clinic
      of a Nigerian Tertiary Hospital.
AB  - Although the negative impact of pain on the quality of life of patients living
      with HIV has been documented in many Western studies, there is a paucity of data
      on pain in HIV-infected patients in Nigeria in spite of a large disease burden.
      We studied the frequency of pain as a symptom and determined the body regions
      often affected among our cohort of patients attending the antiretroviral (ARV)
      clinic. An interviewer-administered questionnaire was used to obtain information
      on presence of pain in the 2 weeks before the interview. Those with pain were
      further screened with the modified Brief Pain Inventory. There were 79
      respondents-40.5% males, mean age 37.1 +/- 8.6 years. Pain was present in 22
      (27.8%) of the respondents. The major regions affected by pain were lower limbs
      (40.9%), head and neck (31.8%), and abdomen (31.8%). Only 40% of those with
      moderate to severe pain intensity reported being on any form of analgesia.

PMID- 21075910
TI  - A small-molecule inhibitor of MDMX activates p53 and induces apoptosis.
AB  - The p53 inactivation caused by aberrant expression of its major regulators (e.g.,
      MDM2 and MDMX) contributes to the genesis of a large number of human cancers.
      Recent studies have shown that restoration of p53 activity by counteracting p53
      repressors is a promising anticancer strategy. Although agents (e.g., nutlin-3a)
      that disrupt MDM2-p53 interaction can inhibit tumor growth, they are less
      effective in cancer cells that express high levels of MDMX. MDMX binds to p53 and
      can repress the tumor suppressor function of p53 through inhibiting its trans
      activation activity and/or destabilizing the protein. Here we report the
      identification of a benzofuroxan derivative [7-(4-methylpiperazin-1-yl)-4-nitro-1
      oxido-2,1,3-benzoxadiazol-1-ium, NSC207895] that could inhibit MDMX expression in
      cancer cells through a reporter-based drug screening. Treatments of MCF-7 cells
      with this small-molecule MDMX inhibitor activated p53, resulting in elevated
      expression of proapoptotic genes (e.g., PUMA, BAX, and PIG3). Importantly, this
      novel small-molecule p53 activator caused MCF-7 cells to undergo apoptosis and
      acted additively with nutlin-3a to activate p53 and decrease the viability of
      cancer cells. These results thus show that small molecules targeting MDMX
      expression would be of therapeutic benefits.

PMID- 21075913
TI  - Prevalence of and risk factors for pre-diabetes in HIV-1-infected patients in
      Bangkok, Thailand.
AB  - Pre-diabetes substantially increases the risk of developing macrovascular
      complication and progression to diabetes. This study aimed to determine the
      prevalence of and risk factors for pre-diabetes in HIV-1-infected patients. A
      cross-sectional study was conducted in HIV-1-infected patients who visited the
      infectious diseases clinic in a university hospital. Fasting plasma glucose (FPG)
      was performed. There were 149 patients, mean age 42.2 years, and 65.1% were
      males. Median CD4 count was 434 cells/mm(3). In total, 92% have received
      antiretroviral therapy (ART), with a median duration of 0.8 years. The prevalence
      of pre-diabetes was 27.5%. From multivariate analysis, body weight ([BW] per 5 kg
      increase, odds ratio [OR] = 1.241; 95% confidence interval [CI], 1.014-1.518; P =
      .036) and, tentatively, male gender (OR = 2.906; 95% CI, 0.941-8.976; P = .064)
      were risk factors for pre-diabetes. Nevirapine (NVP) use (OR = 0.383; 95% CI,
      0.161-0.910; P = .030) was a protective factor for pre-diabetes. Pre-diabetes is
      common in HIV-1-infected patients receiving ART. Screening for pre-diabetes and
      active management should be performed in patients with risk factors.

PMID- 21075912
TI  - Pilot study: does lower extremity night splinting assist in the management of
      painful peripheral neuropathy in the HIV/AIDS population?
AB  - INTRODUCTION: The pain associated with peripheral neuropathy (PN) observed in
      patients living with HIV/AIDS represents a difficult complication to manage.
      PARTICIPANTS: A total of 22 participants with a diagnosis of PN were recruited to
      assess the effects of using night splints on pain and sleep quality. METHODS: For
      3 weeks, the participants were instructed to use bilateral night splints and
      given an exercise regimen for 3 additional weeks. Scores from pain and sleep
      questionnaires were analyzed using repeated measures analysis of variance
      (ANOVA). RESULTS: The change in pain scores (F(1.16) = 13.41,eta(2) =.456, P =
      .002) and sleep index scores (z = -2.69, P = .004, 1-tailed) was found to be
      significant following the use of night splints. No difference was found with the
      use of the exercises. DISCUSSION: The use of night splints in HIV-infected
      patients with PN represents an additional tool for managing pain and improving
      sleep.

PMID- 21075914
TI  - Adherence to antiretroviral therapy in an urban, free-care HIV clinic in
      Guatemala City, Guatemala.
AB  - BACKGROUND: Numerous studies have demonstrated that, in addition to inherent
      qualities of antiretroviral (ARV) medications, adherence is affected by
      demographic, socioeconomic, and psychological factors. There are limited data
      about factors affecting adherence to antiretroviral therapy (ART) among HIV
      infected persons in urban Guatemalan HIV care centers. METHODS: Participants were
      patients at an urban, free-care public clinic in Guatemala City and obtained
      medications from a closed-pharmacy system. Nonpregnant patients >=18 years who
      received medications from the Global Fund to Fight AIDS, Tuberculosis & Malaria,
      who had taken ARV medications for >=12 weeks, who arrived for an appointment at
      the clinic, and who provided informed consent were interviewed. Adherence was
      measured using pharmacy pill counts and patient self-reports. Recent biological
      markers for each patient were collected from the clinic's database, and chi( 2)
      and descriptive statistics were used to analyze results. RESULTS: Among 122
      patients interviewed, mean adherence by pill count was 97%. A total of 110
      patients (90%) had adherence >=95% using pharmacy pill counts, and 108 (89%) had
      adherence >=95% using self-reports. Virologic failure (viral load [VL] >=500
      copies/mL) was significantly less common among patients with >=95% adherence (P =
      .02). Family and spousal support for treatment were significantly associated with
      >=95% adherence (P = .01 and .003, respectively). The presence of stavudine (d4T)
      in a patient's regimen was significantly associated with <95% adherence according
      to self-reports (P < .01). The most common self-reported cause for missing
      medications was forgetfulness, followed by leaving medications at home. Inability
      to travel to the clinic was a major cause of missing medications, and only 51
      patients (41.8%) reported always having sufficient economic resources to reach
      the clinic for appointments and to refill prescriptions. CONCLUSIONS: In this
      urban Central American population, high levels of adherence were measured by both
      self-report and pharmacy pill count. Socioeconomic and demographic conditions
      associated with adherence and specific reasons for missing medications were
      identified.

PMID- 21075915
TI  - Influence of trust on HIV diagnosis and care practices: a literature review.
AB  - Delays in accessing HIV health care and failure to adhere to providers' advice
      are common. Patient trust is critical to an individual's willingness to seek care
      and follow the physician's advice. Conversely, patient distrust can diminish the
      patient's health status. The trust literature is reviewed in an attempt to
      determine its effect on HIV care. In the HIV literature reviewed, greater trust
      in health care providers was associated with improved accessing of and remaining
      in care. Interventions to enhance patient trust have been tested, with no changes
      in the levels of trust being found. Few studies were rigorous enough to assess
      causality or temporal relation. It is not clear whether there is a causal
      association between patient trust and HIV health care outcomes. As these
      relationships are better understood, interventions can be designed to increase
      health-promoting behaviors.

PMID- 21075916
TI  - Continuing education course #3: current practices and future trends in
      neuropathology assessment for developmental neurotoxicity testing.
AB  - The continuing education course on Developmental Neurotoxicity Testing (DNT) was
      designed to communicate current practices for DNT neuropathology, describe
      promising innovations in quantitative analysis and noninvasive imaging, and
      facilitate a discussion among experienced neuropathologists and regulatory
      scientists regarding suitable DNT practices. Conventional DNT neuropathology
      endpoints are qualitative histopathology and morphometric endpoints of
      particularly vulnerable sites (e.g., cerebral, cerebellar, or hippocampal
      thickness). Novel imaging and stereology measurements hold promise for automated
      analysis of factors that cannot be effectively examined in routinely processed
      specimens (e.g., cell numbers, fiber tract integrity). The panel recommended that
      dedicated DNT neuropathology data sets be acquired on a minimum of 8 sections
      (for qualitative assessment) or 3 sections (for quantitative linear and
      stereological analyses) using a small battery of stains to examine neurons and
      myelin. Where guidelines permit discretion, immersion fixation is acceptable for
      younger animals (postnatal day 22 or earlier), and peripheral nerves may be
      embedded in paraffin. Frequent concerns regarding DNT data sets include false
      negative outcomes due to processing difficulties (e.g., lack of concordance among
      sections from different animals) and insensitive analytical endpoints (e.g.,
      qualitative evaluation) as well as false-positive results arising from
      overinterpretation or misreading by inexperienced pathologists.

PMID- 21075918
TI  - Fundamentals of neurobiology.
AB  - Session 1 of the 2010 STP/IFSTP Joint Symposium on Toxicologic Neuropathology,
      titled "Fundamentals of Neurobiology," was organized to provide a foundation for
      subsequent sessions by presenting essential elements of neuroanatomy and nervous
      system function. A brief introduction to the session titled "Introduction to
      Correlative Neurobiology" was provided by Dr. Greg Hall (Eli Lilly and Company,
      Indianapolis, IN). Correlative neurobiology refers to considerations of the
      relationships between the highly organized and compartmentalized structure of
      nervous tissues and the functioning within this system.

PMID- 21075917
TI  - Functional assays for neurotoxicity testing.
AB  - Neurobehavioral and pathological evaluations of the nervous system are
      complementary components of basic research and toxicity testing of pharmaceutical
      and environmental chemicals. While neuropathological assessments provide insight
      as to cellular changes in neurons, behavioral and physiological methods evaluate
      the functional consequences of disruption of neuronal communications. The
      underlying causes of certain behavioral alterations may be understood, but many
      do not have known direct associations with specific brain pathologies. In some
      cases, however, rapidly expanding mouse models (transgenic, knock-out) are
      providing considerable information on behavioral phenotypes of altered pathology.
      Behavior represents the integrated sum of activities mediated by the nervous
      system, and functional tests used for neurotoxicity testing tap different
      behavioral repertoires. These tests have an advantage over pathologic measures in
      that they permit repeated evaluation of a single animal over time to determine
      the onset, progression, duration, and reversibility of a neurotoxic injury.
      Functional assays range from a screening-level battery of tests to refined
      procedures to tap specific forms of learning and/or memory. This article reviews
      common procedures for behavioral toxicity testing and provides examples of
      chemical-specific neurobehavioral-pathological correlations in order to inform
      interpretation and integration of neuropathological and behavioral outcomes.

PMID- 21075919
TI  - Perspectives on past practices and future trends in toxicologic neuropathology:
      notes from a keynote address by Dr. Peter S. Spencer.
AB  - Dr. Peter S. Spencer, a pioneering neurotoxicologist of international renown,
      delivered the keynote address at the 2010 Joint Scientific Symposium of the
      Society of Toxicologic Pathology (STP) and the International Federation of
      Societies of Toxicologic Pathologists (IFSTP). He has made many landmark
      discoveries during his four-decade career. Dr. Spencer's address communicated
      several fundamental principles of past and present toxicologic neuropathology
      research, and he also predicted future trends in the field. First, classic
      approaches to toxicologic neuropathology emphasized morphologic techniques such
      as light microscopic and ultrastructural assessment. However, neuropathology
      methods alone rarely reveal the mechanism(s) and etiology of neurotoxic
      conditions, so neurotoxicity problems are now being investigated using a
      multidisciplinary approach in which neuropathologic assessment is but one
      component of the analysis. The two primary trends for future toxicologic
      neuropathology investigations, in both animals and humans, will be an increased
      use of noninvasive neural imaging and greater preference for in situ molecular
      ("omic") methods, which provide functional information in a structural context.
      These trends will significantly enhance the ability of scientists to translate
      animal data to human situations, thereby improving our understanding of disease
      mechanisms and facilitating efforts to design new therapies for neural diseases.

PMID- 21075921
TI  - Genome sequence of Leuconostoc fallax KCTC 3537.
AB  - Leuconostoc fallax is known to be present during the manufacturing process of
      kimchi, the best-known traditional Korean dish. Here, we present the draft genome
      sequence of the type strain Leuconostoc fallax KCTC 3537 (1,638,971 bp, with a
      G+C content of 37.5%), which consists of 30 large contigs (>100 bp in size).

PMID- 21075920
TI  - Role of astrocytes in brain function and disease.
AB  - Astrocytes assume multiple roles in maintaining an optimally suited milieu for
      neuronal function. Select astrocytic functions include the maintenance of redox
      potential, the production of trophic factors, the regulation of neurotransmitter
      and ion concentrations, and the removal of toxins and debris from the
      cerebrospinal fluid (CSF). Impairments in these and other functions, as well as
      physiological reactions of astrocytes to injury, can trigger or exacerbate
      neuronal dysfunction. This review addresses select metabolic interactions between
      neurons and astrocytes and emphasizes the role of astrocytes in mediating and
      amplifying the progression of several neurodegenerative disorders, such as
      Parkinson's disease (PD), hepatic encephalopathy (HE), hyperammonemia (HA),
      Alzheimer's disease (AD), and ischemia.

PMID- 21075922
TI  - Translation efficiency of antiterminator proteins is a determinant for the
      difference in glucose repression of two beta-glucoside phosphotransferase system
      gene clusters in Corynebacterium glutamicum R.
AB  - Corynebacterium glutamicum R has two beta-glucoside phosphoenolpyruvate,
      carbohydrate phosphotransferase systems (PTS) encoded by bglF and bglF2 located
      in the respective clusters, bglF-bglA-bglG and bglF2-bglA2-bglG2. Previously, we
      reported that whereas beta-glucoside-dependent induction of bglF is strongly
      repressed by glucose, glucose repression of bglF2 is very weak. Here, we reveal
      the mechanism behind the different effects of glucose on the two bgl genes.
      Deletion of the ribonucleic antiterminator sequence and transcriptional
      terminator located upstream of the translation initiation codon of bglF markedly
      relieved the glucose repression of a bglF-lacZ fusion, indicating that glucose
      affects the antitermination mechanism that is responsible for the beta-glucoside
      dependent induction of the bglF cluster. The glucose repression of bglF mRNA was
      also relieved by introducing a multicopy plasmid carrying the bglG gene encoding
      an antiterminator of the bglF cluster. Moreover, replacement of the GUG
      translation initiation codon of bglG with AUG was effective in relieving the
      glucose repression of bglF and bglG. Inversely, expression of bglF2 and bglG2 was
      subject to strict glucose repression in a mutant strain in which the AUG
      translation initiation codon of bglG2 encoding antiterminator of the bglF2
      cluster was replaced with GUG. These results suggest that the translation
      initiation efficiency of the antiterminator proteins, at least in part,
      determines whether the target genes are subject to glucose repression. We also
      found that bglF expression was induced by glucose in the BglG-overexpressing
      strains, which may be explained by the ability of BglF to transport glucose.

PMID- 21075923
TI  - Fur negatively regulates hns and is required for the expression of HilA and
      virulence in Salmonella enterica serovar Typhimurium.
AB  - Iron is an essential element for the survival of living cells. However, excess
      iron is toxic, and its uptake is exquisitely regulated by the ferric uptake
      regulator, Fur. In Salmonella, the Salmonella pathogenicity island 1 (SPI-1)
      encodes a type three secretion system, which is required for invasion of host
      epithelial cells in the small intestine. A major activator of SPI-1 is HilA,
      which is encoded within SPI-1. One known regulator of hilA is Fur. The mechanism
      of hilA regulation by Fur is unknown. We report here that Fur is required for
      virulence in Salmonella enterica serovar Typhimurium and that Fur is required for
      the activation of hilA, as well as of other HilA-dependent genes, invF and sipC.
      The Fur-dependent regulation of hilA was independent of PhoP, a known repressor
      of hilA. Instead, the expression of the gene coding for the histone-like protein,
      hns, was significantly derepressed in the fur mutant. Indeed, the activation of
      hilA by Fur was dependent on 28 nucleotides located upstream of hns. Moreover, we
      used chromatin immunoprecipitation to show that Fur bound, in vivo, to the
      upstream region of hns in a metal-dependent fashion. Finally, deletion of fur in
      an hns mutant resulted in Fur-independent activation of hilA. In conclusion, Fur
      activates hilA by repressing the expression of hns.

PMID- 21075924
TI  - argC Orthologs from Rhizobiales show diverse profiles of transcriptional
      efficiency and functionality in Sinorhizobium meliloti.
AB  - Several factors can influence ortholog replacement between closely related
      species. We evaluated the transcriptional expression and metabolic performance of
      ortholog substitution complementing a Sinorhizobium meliloti argC mutant with
      argC from Rhizobiales (Agrobacterium tumefaciens, Rhizobium etli, and
      Mesorhizobium loti). The argC gene is necessary for the synthesis of arginine, an
      amino acid that is central to protein and cellular metabolism. Strains were
      obtained carrying plasmids with argC orthologs expressed under the speB and argC
      (S. meliloti) and lac (Escherichia coli) promoters. Complementation analysis was
      assessed by growth, transcriptional activity, enzymatic activity, mRNA levels,
      specific detection of ArgC proteomic protein, and translational efficiency. The
      argC orthologs performed differently in each complementation, reflecting the
      diverse factors influencing gene expression and the ability of the ortholog
      product to function in a foreign metabolic background. Optimal complementation
      was directly related to sequence similarity with S. meliloti, and was inversely
      related to species signature, with M. loti argC showing the poorest performance,
      followed by R. etli and A. tumefaciens. Different copy numbers of genes and
      amounts of mRNA and protein were produced, even with genes transcribed from the
      same promoter, indicating that coding sequences play a role in the transcription
      and translation processes. These results provide relevant information for further
      genomic analyses and suggest that orthologous gene substitutions between closely
      related species are not completely functionally equivalent.

PMID- 21075925
TI  - Genetic and mass spectrometry analyses of the unusual type IV-like pili of the
      archaeon Methanococcus maripaludis.
AB  - The structure of pili from the archaeon Methanococcus maripaludis is unlike that
      of any bacterial pili. However, genetic analysis of the genes involved in the
      formation of these pili has been lacking until this study. Pili were isolated
      from a nonflagellated (DeltaflaK) mutant and shown by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis to consist primarily of subunits with an
      apparent molecular mass of 17 kDa. In-frame deletions were created in three
      genes, MMP0233, MMP0236, and MMP0237, which encode proteins with bacterial type
      IV pilin-like signal peptides previously identified by in silico methodology as
      likely candidates for pilus structural proteins. Deletion of MMP0236 or MMP0237
      resulted in mutant cells completely devoid of pili on the cell surface, while
      deletion of the third pilin-like gene, MMP0233, resulted in cells greatly reduced
      in the number of pili on the surface. Complementation with the deleted gene in
      each case returned the cells to a piliated state. Surprisingly, mass spectrometry
      analysis of purified pili identified the major structural pilin as another type
      IV pilin-like protein, MMP1685, whose gene is located outside the first pilus
      locus. This protein was found to be glycosylated with an N-linked branched
      pentasaccharide glycan. Deletion and complementation analysis confirmed that
      MMP1685 is required for piliation.

PMID- 21075926
TI  - Type I signal peptidase and protein secretion in Staphylococcus epidermidis.
AB  - Bacterial protein secretion is a highly orchestrated process that is essential
      for infection and virulence. Despite extensive efforts to predict or
      experimentally detect proteins that are secreted, the characterization of the
      bacterial secretome has remained challenging. A central event in protein
      secretion is the type I signal peptidase (SPase)-mediated cleavage of the N
      terminal signal peptide that targets a protein for secretion via the general
      secretory pathway, and the arylomycins are a class of natural products that
      inhibit SPase, suggesting that they may be useful chemical biology tools for
      characterizing the secretome. Here, using an arylomycin derivative, along with
      two-dimensional gel electrophoresis and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS), we identify 11 proteins whose secretion from stationary
      phase Staphylococcus epidermidis is dependent on SPase activity, 9 of which are
      predicted to be translated with canonical N-terminal signal peptides. In
      addition, we find that the presence of extracellular domains of lipoteichoic acid
      synthase (LtaS) and the beta-lactam response sensor BlaR1 in the medium is
      dependent on SPase activity, suggesting that they are cleaved at noncanonical
      sites within the protein. In all, the data define the proteins whose stationary
      phase secretion depends on SPase and also suggest that the arylomycins should be
      valuable chemical biology tools for the study of protein secretion in a wide
      variety of different bacteria.

PMID- 21075927
TI  - XerCD-mediated site-specific recombination leads to loss of the 57-kilobase
      gonococcal genetic island.
AB  - Most strains of Neisseria gonorrhoeae carry the 57-kb gonococcal genetic island
      (GGI), as do a few strains of Neisseria meningitidis. The GGI is inserted into
      the chromosome at the dif site (difA) and is flanked by a partial repeat of the
      dif site (difB). Since dif is a sequence recognized by the site-specific
      recombinases XerC and XerD and the GGI shows evidence of horizontal acquisition,
      we hypothesized that the GGI may be acquired or lost by XerCD-mediated site
      specific recombination. We show that while the GGI flanked by wild-type dif
      sites, difA and difB, is not readily lost from the gonococcal chromosome, the
      substitution of difB with another copy of difA allows the frequent excision and
      loss of the GGI. In mutants carrying two difA sites (difA(+) difA(+)), the GGI
      can be detected as an extrachromosomal circle that exists transiently. A mutation
      of xerD diminished GGI excision from the chromosome of a difA(+) difA(+) strain,
      while mutations in recA or type IV secretion genes had no effect on the loss of
      the GGI. These data indicate that the GGI is maintained by the replication of the
      chromosome and that GGI excision and loss are dependent upon the dif sequence and
      xerD. The detection of a circular form of the GGI in a wild-type strain suggests
      that GGI excision may occur naturally and could function to facilitate GGI
      transfer. These data suggest a model of GGI excision and loss explaining the
      absence of the GGI from some gonococcal strains and the maintenance of variant
      GGIs in some gonococcal and meningococcal isolates.

PMID- 21075929
TI  - Opposing contributions of polynucleotide phosphorylase and the membrane protein
      NlpI to biofilm formation by Salmonella enterica serovar Typhimurium.
AB  - CsgD and cyclic-3',5'-di-guanylate are key regulators of biofilm formation in
      Salmonella enterica serovar Typhimurium. Our results show that polynucleotide
      phosphorylase and NlpI oppositely altered expression of CsgD. Polynucleotide
      phosphorylase and NlpI also had opposite effects on the expression of yjcC, which
      codes for a cyclic-3',5'-di-guanylate phosphodiesterase affecting CsgD
      expression.

PMID- 21075928
TI  - Aerobic degradation of mercaptosuccinate by the gram-negative bacterium
      Variovorax paradoxus strain B4.
AB  - The Gram-negative bacterium Variovorax paradoxus strain B4 was isolated from soil
      under mesophilic and aerobic conditions to elucidate the so far unknown
      catabolism of mercaptosuccinate (MS). During growth with MS this strain released
      significant amounts of sulfate into the medium. Tn5::mob-induced mutagenesis was
      successfully employed and yielded nine independent mutants incapable of using MS
      as a carbon source. In six of these mutants, Tn5::mob insertions were mapped in a
      putative gene encoding a molybdenum (Mo) cofactor biosynthesis protein (moeA). In
      two further mutants the Tn5::mob insertion was mapped in the gene coding for a
      putative molybdopterin (MPT) oxidoreductase. In contrast to the wild type, these
      eight mutants also showed no growth on taurine. In another mutant a gene
      putatively encoding a 3-hydroxyacyl-coenzyme A dehydrogenase (paaH2) was
      disrupted by transposon insertion. Upon subcellular fractionation of wild-type
      cells cultivated with MS as sole carbon and sulfur source, MPT oxidoreductase
      activity was detected in only the cytoplasmic fraction. Cells grown with
      succinate, taurine, or gluconate as a sole carbon source exhibited no activity or
      much lower activity. MPT oxidoreductase activity in the cytoplasmic fraction of
      the Tn5::mob-induced mutant Icr6 was 3-fold lower in comparison to the wild type.
      Therefore, a new pathway for MS catabolism in V. paradoxus strain B4 is proposed:
      (i) MPT oxidoreductase catalyzes the conversion of MS first into sulfinosuccinate
      (a putative organo-sulfur compound composed of succinate and a sulfino group) and
      then into sulfosuccinate by successive transfer of oxygen atoms, (ii)
      sulfosuccinate is cleaved into oxaloacetate and sulfite, and (iii) sulfite is
      oxidized to sulfate.

PMID- 21075930
TI  - Complete genome sequence of adherent invasive Escherichia coli UM146 isolated
      from Ileal Crohn's disease biopsy tissue.
AB  - Escherichia coli UM146 was isolated from the ileum of a Crohn's disease patient.
      It adheres to and invades enterocytes and can replicate inside macrophages. Its
      complete genome sequence reveals that it is most closely related to the human
      urinary tract pathogen E. coli CFT073, but it has a host of genes that are novel
      and to which no function has been ascribed.

PMID- 21075932
TI  - Genome sequence of the Marine Janibacter Sp. Strain HTCC2649.
AB  - Janibacter sp. strain HTCC2649 is a novel marine member of the Actinobacteria,
      family Intrasporangiaceae, and is closely related to Janibacter melonis CM2104(T)
      and Knoellia sinensis HKI 0119(T). The organism was isolated from a sample
      collected at Hydrostation S south of Bermuda by using high-throughput culturing
      techniques. Here we present the genome sequence of Janibacter sp. strain
      HTCC2649.

PMID- 21075931
TI  - MexT regulates the type III secretion system through MexS and PtrC in Pseudomonas
      aeruginosa.
AB  - The type III secretion system (T3SS) is the most important virulence factor in
      Pseudomonas aeruginosa, and its expression level varies in different isolates. We
      studied the molecular basis for such differences in two laboratory strains, PAK
      and PAO1. A chromosomal clone library from the high-T3SS-producer strain PAK was
      introduced into the low-producer strain PAO1, and we found that a mexS gene from
      PAK confers high T3SS expression in the PAO1 background. Further tests
      demonstrated that both mexS and its neighboring mexT gene are required for the
      repression of the T3SS in PAO1, while the PAK genome encodes a defective MexS,
      accounting for the derepression of the T3SS in PAK and the dominant negative
      effect when it is introduced into PAO1. MexS is a probable oxidoreductase whose
      expression is dependent on MexT, a LysR-type transcriptional regulator. Various
      genetic data support the idea that MexS modulates the transcriptional regulator
      function of MexT. In searching for the MexT-dependent repressor of the T3SS, a
      small gene product of PA2486 (ptrC) was found effective in suppressing the T3SS
      upon overexpression. However, deletion of ptrC in the PAO1 background did not
      result in derepression of the T3SS, indicating the presence of another repressor
      for the T3SS. Interestingly, overexpression of functional mexS alone was
      sufficient to repress T3SS even in the absence of MexT, suggesting that MexS is
      another mediator of MexT-dependent T3SS repression. Overexpression of mexS alone
      had no effect on the well-known MexT-dependent genes, including those encoding
      MexEF efflux pump, elastase, and pyocyanin, indicating alternative regulatory
      mechanisms. A model has been proposed for the MexS/MexT-mediated regulation of
      the T3SS, the MexEF efflux pump, and the production of elastase and pyocyanin.

PMID- 21075933
TI  - Complete genome sequence of Japanese erwinia strain ejp617, a bacterial shoot
      blight pathogen of pear.
AB  - The Japanese Erwinia strain Ejp617 is a plant pathogen that causes bacterial
      shoot blight of pear in Japan. Here, we report the complete genome sequence of
      strain Ejp617 isolated from Nashi pears in Japan to provide further valuable
      insight among related Erwinia species.

PMID- 21075934
TI  - Charlie Ellington FRS retires.

PMID- 21075935
TI  - The effects of arm swing on human gait stability.
AB  - Arm swing during human gait has been shown to reduce both angular momentum about
      the vertical and energy expenditure, and has been hypothesized to enhance gait
      stability. To examine this hypothesis, we studied the effect of arm swing on the
      local and global stability of steady-state gait, as well as the ability to
      perform adequate recovery actions following a perturbation. Trunk kinematics of
      11 male subjects was measured in treadmill walking with normal and with
      restricted arm swing. In half of the trials, gait was perturbed by a position
      controlled forward pull to the trunk. We constructed state spaces using data
      recorded from the unperturbed steady-state walking trials, and quantified local
      gait stability by calculating maximum Lyapunov exponents. In addition, we
      analyzed perturbation forces, the distance from the unperturbed gait pattern, and
      the return toward the normal gait pattern following an external perturbation.
      Walking without arm swing led to a non-significantly lower Lyapunov exponent
      (P=0.06), significantly higher perturbation forces (P<0.05), and significantly
      slower movements away from the attractor (P<0.01). These results suggest that
      gait without arm swing is characterized by similar local stability to gait with
      arm swing and a higher perturbation resistance. However, return towards the
      normal gait pattern was significantly slower (P<0.05) when walking with
      restricted arms, suggesting that the arms play an important role in the recovery
      from a perturbation. Collectively, the results suggest that arm swing as such
      does not enhance gait stability, but rather that recovery movements of the arms
      contribute to the overall stability of human gait.

PMID- 21075936
TI  - Night vision by cuttlefish enables changeable camouflage.
AB  - Because visual predation occurs day and night, many predators must have good
      night vision. Prey therefore exhibit antipredator behaviours in very dim light.
      In the field, the giant Australian cuttlefish (Sepia apama) assumes camouflaged
      body patterns at night, each tailored to its immediate environment. However, the
      question of whether cuttlefish have the perceptual capability to change their
      camouflage at night (as they do in day) has not been addressed. In this study,
      we: (1) monitored the camouflage patterns of Sepia officinalis during the
      transition from daytime to night-time using a natural daylight cycle and (2)
      tested whether cuttlefish on a particular artificial substrate change their
      camouflage body patterns when the substrate is changed under dim light (down to
      starlight, 0.003 lux) in a controlled light field in a dark room setting. We
      found that cuttlefish camouflage patterns are indeed adaptable at night: animals
      responded to a change in their visual environment with the appropriate body
      pattern change. Whether to deceive their prey or predators, cuttlefish use their
      excellent night vision to perform adaptive camouflage in dim light.

PMID- 21075937
TI  - Diel foraging behavior of gravid leatherback sea turtles in deep waters of the
      Caribbean Sea.
AB  - It is generally assumed that leatherback turtles (Dermochelys coriacea), like
      other species of sea turtle, do not feed while offshore from nesting beaches, and
      rely instead on fat reserves to fuel reproductive activities. Recent studies,
      however, provide evidence that leatherbacks may forage during the internesting
      interval while offshore in the Western Atlantic Ocean and Caribbean Sea. Bio
      logging technology was used to investigate the foraging behavior of female
      leatherback turtles at St Croix, US Virgin Islands. Leatherback gastrointestinal
      tract temperatures (T(GT)) were analyzed for sudden fluctuations indicative of
      ingestions, and laboratory ingestion simulations were used to characterize
      temperature fluctuations associated with ingestion of prey versus seawater. Dive
      patterns associated with prey ingestion were characterized and the proportion of
      prey ingestion during the day (05:00-18:59 h) and night (19:00-04:59 h) were
      compared. A combined total of 111 prey ingestions for seven leatherback turtles
      were documented during the internesting interval. The number of prey ingestions
      ranged from six to 48 for individual turtles, and the majority (87.4%) of these
      events occurred during the daytime. Prey ingestions were most frequently
      associated with V-shaped dives, and the mean (+/-1 s.d.) maximum dive depth with
      prey ingestion ranged from 154+/-51 to 232+/-101 m for individual turtles.
      Although leatherbacks were found to opportunistically feed during the
      internesting interval, the low prey ingestion rates indicate that energy reserves
      acquired prior to the breeding season are critical for successful reproduction by
      leatherbacks from the St Croix, USVI nesting population.

PMID- 21075938
TI  - The mass-specific energy cost of human walking is set by stature.
AB  - The metabolic and mechanical requirements of walking are considered to be of
      fundamental importance to the health, physiological function and even the
      evolution of modern humans. Although walking energy expenditure and gait
      mechanics are clearly linked, a direct quantitative relationship has not emerged
      in more than a century of formal investigation. Here, on the basis of previous
      observations that children and smaller adult walkers expend more energy on a per
      kilogram basis than larger ones do, and the theory of dynamic similarity, we
      hypothesized that body length (or stature, L(b)) explains the apparent body-size
      dependency of human walking economy. We measured metabolic rates and gait
      mechanics at six speeds from 0.4 to 1.9 m s(-1) in 48 human subjects who varied
      by a factor of 1.5 in stature and approximately six in both age and body mass. In
      accordance with theoretical expectation, we found the most economical walking
      speeds measured (J kg(-1) m(-1)) to be dynamically equivalent (i.e. similar U,
      where U=velocity(2)/gravity . leg length) among smaller and larger individuals.
      At these speeds, stride lengths were directly proportional to stature whereas the
      metabolic cost per stride was largely invariant (2.74+/-0.12 J kg(-1) stride(
      1)). The tight coupling of stature, gait mechanics and metabolic energy
      expenditure resulted in an inverse relationship between mass-specific transport
      costs and stature (E(trans)/M(b)?L(b)(-0.95), J kg(-1) m(-1)). We conclude that
      humans spanning a broad range of ages, statures and masses incur the same mass
      specific metabolic cost to walk a horizontal distance equal to their stature.

PMID- 21075939
TI  - Chemo-accumulation without changes in membrane potential in the microstome form
      of the ciliate Tetrahymena vorax.
AB  - The swimming behaviour of ciliates is mainly determined by membrane potential and
      transmembrane fluxes. In a chemical gradient, swimming ciliates may approach or
      move away from the source. Based on experiments on Paramecium, it is generally
      assumed that chemical attractants and repellents affect the swimming behaviour of
      ciliates by specific changes in the membrane potential. We have examined whether
      there is a causal relationship between membrane potential and chemo-accumulation
      in the microstome form of the polymorphic ciliate Tetrahymena vorax. Effects of
      chemo-attractants on the membrane potential of Tetrahymena have not been
      previously reported. Microstome T. vorax cells aggregated close to a point source
      of l-cysteine and the complex meat hydrolysate proteose peptone. Chemo
      accumulated cells displayed a significantly higher turning frequency than control
      cells at a similar cell density. A concentration of 20 mmol l(-1) l-cysteine did
      not evoke any detectable change in the membrane potential whereas 1% proteose
      peptone depolarised the cells by ~12 mV. This is contrary to the current model,
      which predicts agents that induce a moderate depolarisation to be repellents. A
      solution of 1% proteose peptone contains 21 mmol(-1) Na(+). A solution of 21
      mmol(-1) NaCl without organic compounds also caused ~12 mV depolarisation but had
      no aggregating effect on the cells. Collectively, the electrophysiological and
      behavioural data indicate that chemo-accumulation in the microstome form of T.
      vorax is not governed obligatorily by the membrane potential. We thus suggest
      that the simple membrane potential model for chemokinesis in Paramecium may not
      be valid for T. vorax.

PMID- 21075940
TI  - The energy budget, thermogenic capacity and behavior in Swiss mice exposed to a
      consecutive decrease in temperatures.
AB  - The limitation on sustainable energy intake (SusEI) is important because it
      establishes the upper energetic limit on the ability of animals to disperse,
      survive and reproduce. However, there are still arguments about what factors
      impose that limitation. Thermoregulation in cold environments imposes great
      energy demands on small mammals. A cold-exposed animal has been suggested to be a
      model suitable for testing these factors. Here, we examined the changes in food
      intake and digestible energy intake (DEI) as measures of SusEI, thermogenic
      capacity and behavioral patterns in Swiss mice exposed to consecutively lower
      ambient temperatures from 23 to -15 degrees C. Cold-exposed mice showed
      significant decreases in body mass, fat content of the carcass and body
      temperature, and increases in DEI compared with controls. The time spent on
      feeding significantly increased with decreasing temperatures, and time spent on
      general activity decreased following cold exposure. Resting metabolic rate,
      nonshivering thermogenesis and serum tri-iodothyronine levels significantly
      increased in mice exposed to lower temperatures in comparison with controls,
      whereas these thermogenic variables were not significantly different between 0
      and -15 degrees C. It might suggest that SusEI in cold exposed Swiss mice was
      constrained peripherally by the capacity to produce heat and also by the ability
      to dissipate body heat, but to a different extent. Moderate cold exposure might
      result in a relaxation of the heat dissipation limit (HDL), allowing the animals
      to increase food intake to meet cold stress. When animals are exposed to severe
      cold, the thermogenenic capacity might reach a ceiling, failing to compensate for
      the heat loss and which would finally result in lower body temperature and
      considerable weight loss. This might indicate that the HDL was set at a higher
      level than peripheral limits for Swiss mice exposed to a consecutive decrease in
      ambient temperatures.

PMID- 21075941
TI  - Relationship between muscle forces, joint loading and utilization of elastic
      strain energy in equine locomotion.
AB  - Storage and utilization of strain energy in the elastic tissues of the distal
      forelimb of the horse is thought to contribute to the excellent locomotory
      efficiency of the animal. However, the structures that facilitate elastic energy
      storage may also be exposed to dangerously high forces, especially at the fastest
      galloping speeds. In the present study, experimental gait data were combined with
      a musculoskeletal model of the distal forelimb of the horse to determine muscle
      and joint contact loading and muscle-tendon work during the stance phase of
      walking, trotting and galloping. The flexor tendons spanning the
      metacarpophalangeal (MCP) joint - specifically, the superficial digital flexor
      (SDF), interosseus muscle (IM) and deep digital flexor (DDF) - experienced the
      highest forces. Peak forces normalized to body mass for the SDF were 7.3+/-2.1,
      14.0+/-2.5 and 16.7+/-1.1 N kg(-1) in walking, trotting and galloping,
      respectively. The contact forces transmitted by the MCP joint were higher than
      those acting at any other joint in the distal forelimb, reaching 20.6+/-2.8,
      40.6+/-5.6 and 45.9+/-0.9 N kg(-1) in walking, trotting and galloping,
      respectively. The tendons of the distal forelimb (primarily SDF and IM)
      contributed between 69 and 90% of the total work done by the muscles and tendons,
      depending on the type of gait. The tendons and joints that facilitate storage of
      elastic strain energy in the distal forelimb also experienced the highest loads,
      which may explain the high frequency of injuries observed at these sites.

PMID- 21075943
TI  - Lack of prediction for high-temperature exposures enhances Drosophila place
      learning.
AB  - Animals receive rewards and punishments in different patterns. Sometimes stimuli
      or behaviors can become predictors of future good or bad events. Through
      learning, experienced animals can then avoid new but similar bad situations, or
      actively seek those conditions that give rise to good results. Not all good or
      bad events, however, can be accurately predicted. Interestingly, unpredicted
      exposure to presumed rewards or punishments can inhibit or enhance later
      learning, thus linking the two types of experiences. In Drosophila, place
      memories can be readily formed; indeed, memory was enhanced by exposing flies to
      high temperatures that are unpaired from place or behavioral contingencies.
      Whether it is the exposure to high temperatures per se or the lack of prediction
      about the exposure that is crucial for memory enhancement is unknown. Through
      yoking experiments, we show that the uncertainty about exposure to high
      temperatures positively biases later place memory. However, the unpredicted
      exposures to high temperature do not alter thermosensitivity. Thus, the
      uncertainty bias does not alter thermosensory processes. An unidentified system
      is proposed to buffer the high-temperature reinforcement information to influence
      place learning when accurate predictions can be identified.

PMID- 21075942
TI  - Response of the Pacific oyster Crassostrea gigas, Thunberg 1793, to pesticide
      exposure under experimental conditions.
AB  - Pesticide run-off into the ocean represents a potential threat to marine
      organisms, especially bivalves living in coastal environments. However, little is
      known about the effects of environmentally relevant concentrations of pesticides
      at the individual level. In this study, the suppression subtractive hybridisation
      technique was used to discover the main physiological function affected by a
      cocktail of three pesticides (lindane, metolachlor and carbofuran) in the Pacific
      oyster Crassostrea gigas. Two oyster populations exposed to different pollution
      levels in the wild were investigated. The pesticide concentrations used to induce
      stress were close to those found in the wild. In a time course experiment, the
      expression of three genes implicated in iron metabolism and oxidative stress as
      well as that of two ubiquitous stress proteins was examined. No clear regulation
      of gene or protein expression was found, potentially due to a low-dose effect.
      However, we detected a strong site- and organ-specific response to the
      pesticides. This study thus (1) provides insight into bivalve responses to
      pesticide pollution at the level of the transcriptome, which is the first level
      of response for organisms facing pollution, and (2) raises interesting questions
      concerning the importance of the sites and organs studied in the toxicogenomic
      field.

PMID- 21075944
TI  - Eyes with basic dorsal and specific ventral regions in the glacial Apollo,
      Parnassius glacialis (Papilionidae).
AB  - Recent studies on butterflies have indicated that their colour vision system is
      almost species specific. To address the question of how this remarkable diversity
      evolved, we investigated the eyes of the glacial Apollo, Parnassius glacialis, a
      living fossil species belonging to the family Papilionidae. We identified four
      opsins in the Parnassius eyes--an ultraviolet- (PgUV), a blue- (PgB), and two
      long wavelength (PgL2, PgL3)-absorbing types--and localized their mRNAs within
      the retina. We thus found ommatidial heterogeneity and a clear dorso-ventral
      regionalization of the eye. The dorsal region consists of three basic types of
      ommatidia that are similar to those found in other insects, indicating that this
      dorsal region retains the ancestral state. In the ventral region, we identified
      two novel phenomena: co-expression of the opsins of the UV- and B-absorbing type
      in a subset of photoreceptors, and subfunctionalization of long-wavelength
      receptors in the distal tier as a result of differential expression of the PgL2
      and PgL3 mRNAs. Interestingly, butterflies from the closely related genus Papilio
      (Papilionidae) have at least three long-wavelength opsins, L1-L3. The present
      study indicates that the duplication of L2 and L3 occurred before the Papilio
      lineage diverged from the rest, whereas L1 was produced from L3 in the Papilio
      lineage.

PMID- 21075945
TI  - Plant cues for aphid navigation in vascular tissues.
AB  - The ability of aphids to detect and find sieve tubes suggests that aphids receive
      cues for sieve-tube recognition by taking samples. Specific natural conditions
      such as pH value, sugar species and concentration, viscosity, and oxygen pressure
      may enable sieve-tube detection. We tested the preference of Megoura viciae and
      Myzus persicae for potential plant-borne orientation parameters in artificial
      choice-chamber systems. Both species preferred sucrose (in comparison with
      fructose, glucose, raffinose or sorbitol) at concentrations of 15-22.5% (over a
      tested range of 0-22.5%) and at approximately pH 7 (over a tested range of pH 5
      8). This preference matches the composition of the sieve-tube sap of their host
      plants. Likewise, Rhopalosiphum padi (normally found on barley plants with
      sucrose in the phloem sap) and Macrosiphum euphorbiae (normally found on pumpkin
      plants with raffinose-family oligosaccharides in the phloem sap) showed a
      significant preference for sucrose. In the absence of sucrose, however, M.
      euphorbiae strongly preferred raffinose. No clear preference for any carbohydrate
      was observed for Macrosiphum rosae and Aphis pomi (both normally found on plants
      with various amounts of sorbitol in the phloem sap). Electrical penetration graph
      (EPG) measurements of M. persicae feeding on artificial diets confirmed that
      sieve tubes are recognized solely by a combination of carbohydrate abundance and
      a neutral to slightly alkaline pH.

PMID- 21075946
TI  - The effect of fin ray flexural rigidity on the propulsive forces generated by a
      biorobotic fish pectoral fin.
AB  - A biorobotic pectoral fin was developed and used to study how the flexural
      rigidities of fin rays within a highly deformable fish fin affect the fin's
      propulsive forces. The design of the biorobotic fin was based on a detailed
      analysis of the pectoral fin of the bluegill sunfish (Lepomis macrochirus). The
      biorobotic fin was made to execute the kinematics used by the biological fin
      during steady swimming, and to have structural properties that modeled those of
      the biological fin. This resulted in an engineered fin that had a similar
      interaction with the water as the biological fin and that created close
      approximations of the three-dimensional motions, flows, and forces produced by
      the sunfish during low speed, steady swimming. Experimental trials were conducted
      during which biorobotic fins of seven different stiffness configurations were
      flapped at frequencies from 0.5 to 2.0 Hz in flows with velocities that ranged
      from 0 to 270 mm s(-1). During these trials, thrust and lift forces were
      measured, kinematics were recorded in three dimensions, and digital particle
      image velocimetry was used to evaluate flow hydrodynamics. The results of the
      trials revealed that slight changes to the fin's mechanical properties or to the
      operating conditions can have significant impact on the direction, magnitude and
      time course of the propulsive forces. In general, the magnitude of the 2-D
      (thrust and lift) propulsive force scaled with fin ray stiffness, and increased
      as the fin's flapping speed increased or as the velocity of the flow decreased.

PMID- 21075947
TI  - Ballistic movements of jumping legs implemented as variable components of cricket
      behaviour.
AB  - Ballistic accelerations of a limb or the whole body require special joint
      mechanisms in many animals. Specialized joints can be moved by stereotypic or
      variable motor control during motor patterns with and without ballistic
      components. As a model of variable motor control, the specialized femur-tibia
      (knee) joints of cricket (Acheta domesticus) hindlegs were studied during
      ballistic kicking, jumping and swimming and in non-ballistic walking. In this
      joint the tendons of the antagonistic flexor and the extensor muscles attach at
      different distances from the pivot and the opposed lever arms form an angle of
      120 deg. A 10:1 ratio of their effective lever arms at full knee flexion helps to
      prepare for most ballistic extensions: the tension of the extensor can reach its
      peak while it is restrained by flexor co-contraction. In kicks, preparatory
      flexion is rapid and the co-contraction terminates just before knee extensions.
      Therefore, mainly the stored tension of the extensor muscle accelerates the small
      mass of the tibia. Jumps are prepared with slower extensor-flexor co-contractions
      that flex both knees simultaneously and then halt to rotate both legs outward to
      a near horizontal level. From there, catapult extension of both knees accelerates
      the body, supported by continued high frequency motor activity to their tibia
      extensor muscles during the ongoing push-off from the substrate. Premature
      extension of one knee instantly takes load from the lagging leg that extends and
      catches up, which finally results in a straight jump. In swimming, synchronous
      ballistic power strokes of both hindlegs drive the tibiae on a ventral-to
      posterior trajectory through the water, well coordinated with the swimming
      patterns of all legs. In walking, running and climbing the steps of the hindlegs
      range between 45 deg flexion and 125 deg extension and use non-ballistic,
      alternating activity of knee flexor and extensor muscles. Steep climbing requires
      longer bursts from the extensor tibiae muscles when they support the extended
      hindlegs against gravity forces when the body hangs over. All ballistic movements
      of cricket knees are elicited by a basic but variable motor pattern: knee
      flexions by co-contraction of the antagonists prepare catapult extensions with
      speeds and forces as required in the different behaviours.

PMID- 21075948
TI  - Female choice in the red mason bee, Osmia rufa (L.) (Megachilidae).
AB  - Females are often thought to use several cues and more than one modality in
      selection of a mate, possibly because they offer complementary information on a
      mate's suitability. In the red mason bee, Osmia rufa, we investigated the
      criteria a female uses to choose a mating partner. We hypothesized that the
      female uses male thorax vibrations and size as signs of male viability and male
      odor for kin discrimination and assessment of genetic relatedness. We therefore
      compared males that had been accepted by a female for copulation with those
      rejected, in terms of their size, their immediate precopulatory vibrations (using
      laser vibrometry), the genetic relatedness of unmated and mated pairs (using
      microsatellite markers) and emitted volatiles (using chemical analyses). Females
      showed a preference for intermediate-sized males that were slightly larger than
      the modal male size. Furthermore, male precopulatory vibration burst duration was
      significantly longer in males accepted for copulation compared with rejected
      males. Vibrations may indicate vigor and assure that males selected by females
      are metabolically active and healthy. Females preferentially copulated with males
      that were genetically more closely related, possibly to avoid outbreeding
      depression. Volatiles of the cuticular surface differed significantly between
      accepted and rejected males in the relative amounts of certain hydrocarbons,
      although the relationship between male odor and female preference was complex.
      Females may therefore also use differences in odor bouquet to select among males.
      Our investigations show that O. rufa females appear to use multiple cues in
      selecting a male. Future investigations are needed to demonstrate whether odor
      plays a role in kin recognition and how the multiple cues are integrated in mate
      choice by females.

PMID- 21075949
TI  - Behaviour and buoyancy regulation in the deepest-diving reptile: the leatherback
      turtle.
AB  - In the face of the physical and physiological challenges of performing breath
      hold deep dives, marine vertebrates have evolved different strategies. Although
      behavioural strategies in marine mammals and seabirds have been investigated in
      detail, little is known about the deepest-diving reptile - the leatherback turtle
      (Dermochelys coriacea). Here, we deployed tri-axial accelerometers on female
      leatherbacks nesting on St Croix, US Virgin Islands, to explore their diving
      strategy. Our results show a consistent behavioural pattern within dives among
      individuals, with an initial period of active swimming at relatively steep
      descent angles (~-40 deg), with a stroke frequency of 0.32 Hz, followed by a
      gliding phase. The depth at which the gliding phase began increased with the
      maximum depth of the dives. In addition, descent body angles and vertical
      velocities were higher during deeper dives. Leatherbacks might thus regulate
      their inspired air-volume according to the intended dive depth, similar to hard
      shelled turtles and penguins. During the ascent, turtles actively swam with a
      stroke frequency of 0.30 Hz but with a low vertical velocity (~0.40 ms(-1)) and a
      low pitch angle (~+26 deg). Turtles might avoid succumbing to decompression
      sickness ('the bends') by ascending slowly to the surface. In addition, we
      suggest that the low body temperature of this marine ectotherm compared with that
      of endotherms might help reduce the risk of bubble formation by increasing the
      solubility of nitrogen in the blood. This physiological advantage, coupled with
      several behavioural and physical adaptations, might explain the particular
      ecological niche the leatherback turtle occupies among marine reptiles.

PMID- 21075950
TI  - The spectral quality of light is a key driver of photosynthesis and
      photoadaptation in Stylophora pistillata colonies from different depths in the
      Red Sea.
AB  - Depth zonation on coral reefs is largely driven by the amount of downwelling,
      photosynthetically active radiation (PAR) that is absorbed by the symbiotic algae
      (zooxanthellae) of corals. The minimum light requirements of zooxanthellae are
      related to both the total intensity of downwelling PAR and the spectral quality
      of the light. Here we used Stylophora pistillata colonies collected from shallow
      (3 m) and deep (40 m) water; colonies were placed in a respirometer under both
      ambient PAR irradiance and a filter that only transmits blue light. We found that
      the colonies exhibited a clear difference in their photosynthetic rates when
      illuminated under PAR and filtered blue light, with higher photosynthetic
      performance when deep colonies were exposed to blue light compared with full
      spectrum PAR for the same light intensity and duration. By contrast, colonies
      from shallow water showed the opposite trend, with higher photosynthetic
      performances under full-spectrum PAR than under filtered blue light. These
      findings are supported by the absorption spectra of corals, with deeper colonies
      absorbing higher energy wavelengths than the shallow colonies, with different
      spectral signatures. Our results indicate that S. pistillata colonies are
      chromatically adapted to their surrounding light environment, with
      photoacclimation probably occurring via an increase in photosynthetic pigments
      rather than algal density. The spectral properties of the downwelling light are
      clearly a crucial component of photoacclimation that should be considered in
      future transplantation and photoacclimation studies.

PMID- 21075951
TI  - Characterization of mechanisms for Ca2+ and HCO3(-)/CO3(2-) acquisition for shell
      formation in embryos of the freshwater common pond snail Lymnaea stagnalis.
AB  - The freshwater common pond snail Lymnaea stagnalis produces embryos that complete
      direct development, hatching as shell-bearing individuals within 10 days despite
      relatively low ambient calcium and carbonate availability. This development is
      impaired by removal of ambient total calcium but not by removal of bicarbonate
      and/or carbonate. In this study we utilized pharmacological agents to target
      possible acquisition pathways for both Ca(2+) and accumulation of carbonate in
      post-metamorphic, shell-laying embryos. Using whole egg mass flux measurements
      and ion-specific microelectrode analytical techniques, we have demonstrated that
      carbonic anhydrase-catalyzed hydration of CO(2) is central in the acquisition of
      both shell-forming ions because it provides the hydrogen ions for an electrogenic
      vacuolar-type H(+)-ATPase that fuels the uptake of Ca(2+) via voltage-dependent
      Ca(2+) channels and possibly an electrogenic Ca(2+)/1H(+) exchanger.
      Additionally, CO(2) hydration provides an endogenous source of HCO(3)(-). Thus,
      hydration of endogenous CO(2) forms HCO(3)(-) for calcification while hydrogen
      ions are excreted, contributing to continued Ca(2+) uptake, as well as creating
      favorable alkaline internal conditions for calcification. The connections between
      Ca(2+) and HCO(3)(-) acquisition mechanisms that we describe here provide new
      insight into this efficient, embryonic calcification in freshwater.

PMID- 21075952
TI  - Population differences in fever and sickness behaviors in a wild passerine: a
      role for cytokines.
AB  - Immune responses benefit hosts by clearing pathogens, but they also incur
      physiological costs and tissue damage. While wild animals differ in how they
      balance these costs and benefits, the physiological mechanisms underlying such
      differential investment in immunity remain unknown. Uncovering these mechanisms
      is crucial to determining how and where selection acts to shape immunological
      defense. Among free-living song sparrows (Melospiza melodia) in western North
      America, sickness-induced lethargy and fever are more pronounced in Southern
      California than in Washington and Alaska. We brought song sparrows from two
      populations (Southern California and Washington) into captivity to determine
      whether these differences persist in a common environment and what physiological
      signals facilitate such differences. As in free-living sparrows, captive
      California birds exhibited more pronounced fever and lethargy than Washington
      birds in response to lipopolysaccharide, a non-pathogenic antigen that mimics
      bacterial infection. After treatment, the two populations showed similar
      reductions in luteinizing hormone levels, food intake and body mass, although
      treated birds from California lost more breast muscle tissue than treated birds
      from Washington. Moreover, California birds displayed higher bioactivity of
      interleukin-6, a pro-inflammatory cytokine, and marginally higher levels of
      corticosterone, a steroid hormone involved in stress, metabolism and regulating
      inflammatory responses. Our results show that immunological differences between
      these populations cannot be explained by immediate environment alone and may
      reflect genetic, maternal or early-life effects. Additionally, they suggest that
      cytokines play a role in shaping immunological variation among wild vertebrates.

PMID- 21075953
TI  - The effect of body size on the wing movements of pteropodid bats, with insights
      into thrust and lift production.
AB  - In this study we compared the wing kinematics of 27 bats representing six
      pteropodid species ranging more than 40 times in body mass (M(b)=0.0278-1.152
      kg), to determine whether wing posture and overall wing kinematics scaled as
      predicted according to theory. The smallest species flew in a wind tunnel and the
      other five species in a flight corridor. Seventeen kinematic markers on the
      midline and left side of the body were tracked in three dimensions. We used
      phylogenetically informed reduced major axis regression to test for allometry. We
      found that maximum wingspan (b(max)) and maximum wing area (S(max)) scaled with
      more positive allometry, and wing loading (Q(s)) with more negative allometry
      (b(max)?M(b)(0.423); S(max)?M(b)(0.768); Q(s)?M(b)(0.233)) than has been reported
      in previous studies that were based on measurements from specimens stretched out
      flat on a horizontal surface. Our results suggest that larger bats open their
      wings more fully than small bats do in flight, and that for bats, body
      measurements alone cannot be used to predict the conformation of the wings in
      flight. Several kinematic variables, including downstroke ratio, wing stroke
      amplitude, stroke plane angle, wing camber and Strouhal number, did not change
      significantly with body size, demonstrating that many aspects of wing kinematics
      are similar across this range of body sizes. Whereas aerodynamic theory suggests
      that preferred flight speed should increase with mass, we did not observe an
      increase in preferred flight speed with mass. Instead, larger bats had higher
      lift coefficients (C(L)) than did small bats (C(L)?M(b)(0.170)). Also, the slope
      of the wingbeat period (T) to body mass regression was significantly more shallow
      than expected under isometry (T?M(b)(0.180)), and angle of attack (alpha)
      increased significantly with body mass [alpha?log(M(b))7.738]. None of the bats
      in our study flew at constant speed, so we used multiple regression to isolate
      the changes in wing kinematics that correlated with changes in flight speed,
      horizontal acceleration and vertical acceleration. We uncovered several
      significant trends that were consistent among species. Our results demonstrate
      that for medium- to large-sized bats, the ways that bats modulate their wing
      kinematics to produce thrust and lift over the course of a wingbeat cycle are
      independent of body size.

PMID- 21075954
TI  - Sixty years of CA: a cancer journal for clinicians.
AB  - The first issue of CA: A Cancer Journal for Clinicians was published in November
      of 1950. On the 60th anniversary of that date, we briefly review several seminal
      contributions to oncology and cancer control published in our journal during its
      first decade.

PMID- 21075957
TI  - Parent and child agreement on anxiety disorder symptoms using the DISC predictive
      scales.
AB  - Growing recognition of the negative impact of anxiety disorders in the lives of
      youth has made their identification an important clinical task. Multiple
      perspective assessment (e.g., parents, children) is generally considered a
      preferred method in the assessment of anxiety disorder symptoms, although it has
      been generally thought that disagreement between parent and youth ratings of the
      child's emotions is common. This study examined parent and child reports of the
      child's anxiety disorder symptoms using the Diagnostic Interview Schedule for
      Children-Predictive Scales (DISC-PS) in a clinic-referred sample of substance
      using adolescents. Parents and adolescents (N = 480) who were referred for
      substance abuse treatment were screened for anxiety disorder symptoms using the
      DISC-PS at pretreatment. Results suggest similar (low) levels of agreement
      between the parent report and child report versions as found with other anxiety
      symptom and anxiety disorder measures. Findings provide data on multi-informant
      agreement and highlight issues in the use of the DISC-PS to identify anxiety
      problems in youth.

PMID- 21075958
TI  - Examining the factor structure and discriminant validity of the 12-item General
      Health Questionnaire (GHQ-12) among Spanish postpartum women.
AB  - In this study, the authors tested alternative factor models of the 12-item
      General Health Questionnaire (GHQ-12) in a sample of Spanish postpartum women,
      using confirmatory factor analysis. The authors report the results of modeling
      three different methods for scoring the GHQ-12 using estimation methods
      recommended for categorical and binary data. A discriminant function analysis was
      also performed to test the utility of a multiple factor model. A two-phase cross
      sectional study was designed: (a) 1,453 women visiting at 6 weeks postpartum
      completed the GHQ-12 and the Edinburgh Postnatal Depression Scale questionnaire
      and (b) based on the Edinburgh Postnatal Depression Scale outcomes, participants
      were stratified and randomly selected within each stratum for clinical
      evaluation. Using the Likert-type scoring approach, Hankins's one-factor model
      with "method effects" obtained the best fit. In addition, Graetz's three-factor
      model provided little discrimination between diagnostic groups, the factors being
      highly correlated. These results support the presence of only one latent factor
      in the GHQ-12.

PMID- 21075959
TI  - Cyanide, a coproduct of plant hormone ethylene biosynthesis, contributes to the
      resistance of rice to blast fungus.
AB  - Rice (Oryza sativa) plants carrying the Pi-i resistance gene to blast fungus
      Magnaporthe oryzae restrict invaded fungus in infected tissue via hypersensitive
      reaction or response (HR), which is accompanied by rapid ethylene production and
      formation of small HR lesions. Ethylene biosynthesis has been implicated to be
      important for blast resistance; however, the individual roles of ethylene and
      cyanide, which are produced from the precursor 1-aminocyclopropane-1-carboxylic
      acid, remain unevaluated. In this study, we found that Pi-i-mediated resistance
      was compromised in transgenic rice lines, in which ethylene biosynthetic enzyme
      genes were silenced and then ethylene production was inhibited. The compromised
      resistance in transgenic lines was recovered by exogenously applying cyanide but
      not ethephon, an ethylene-releasing chemical in plant tissue. In a susceptible
      rice cultivar, treatment with cyanide or 1-aminocyclopropane-1-carboxylic acid
      induced the resistance to blast fungus in a dose-dependent manner, while ethephon
      did not have the effect. Cyanide inhibited the growth of blast fungus in vitro
      and in planta, and application of flavonoids, secondary metabolites that exist
      ubiquitously in the plant kingdom, enhanced the cyanide-induced inhibition of
      fungal growth. These results suggested that cyanide, whose production is
      triggered by HR in infected tissue, contributes to the resistance in rice plants
      via restriction of fungal growth.

PMID- 21075960
TI  - Leaf functional anatomy in relation to photosynthesis.

PMID- 21075961
TI  - Mechanical properties of plant cell walls probed by relaxation spectra.
AB  - Transformants and mutants with altered cell wall composition are expected to
      display a biomechanical phenotype due to the structural role of the cell wall. It
      is often quite difficult, however, to distinguish the mechanical behavior of a
      mutant's or transformant's cell walls from that of the wild type. This may be due
      to the plant's ability to compensate for the wall modification or because the
      biophysical method that is often employed, determination of simple elastic
      modulus and breakstrength, lacks the resolving power necessary for detecting
      subtle mechanical phenotypes. Here, we apply a method, determination of
      relaxation spectra, which probes, and can separate, the viscoelastic properties
      of different cell wall components (i.e. those properties that depend on the
      elastic behavior of load-bearing wall polymers combined with viscous interactions
      between them). A computer program, BayesRelax, that deduces relaxation spectra
      from appropriate rheological measurements is presented and made accessible
      through a Web interface. BayesRelax models the cell wall as a continuum of
      relaxing elements, and the ability of the method to resolve small differences in
      cell wall mechanical properties is demonstrated using tuber tissue from wild-type
      and transgenic potatoes (Solanum tuberosum) that differ in rhamnogalacturonan I
      side chain structure.

PMID- 21075963
TI  - Cell Biology Symposium: receptors and signaling.

PMID- 21075964
TI  - 2010 Early Career Achievement Awards: recognizing achievement of young scholars
      working to foster the discovery, sharing, and application of knowledge concerning
      the responsible use of animals to enhance human life and well-being.

PMID- 21075962
TI  - MASCP Gator: an aggregation portal for the visualization of Arabidopsis
      proteomics data.
AB  - Proteomics has become a critical tool in the functional understanding of plant
      processes at the molecular level. Proteomics-based studies have also contributed
      to the ever-expanding array of data in modern biology, with many generating Web
      portals and online resources that contain incrementally expanding and updated
      information. Many of these resources reflect specialist research areas with
      significant and novel information that is not currently captured by centralized
      repositories. The Arabidopsis (Arabidopsis thaliana) community is well served by
      a number of online proteomics resources that hold an abundance of functional
      information. These sites can be difficult to locate among a multitude of online
      resources. Furthermore, they can be difficult to navigate in order to identify
      specific features of interest without significant technical knowledge. Recently,
      members of the Arabidopsis proteomics community involved in developing many of
      these resources decided to develop a summary aggregation portal that is capable
      of retrieving proteomics data from a series of online resources on the fly. The
      Web portal is known as the MASCP Gator and can be accessed at the following
      address: http://gator.masc-proteomics.org/. Significantly, proteomics data
      displayed at this site retrieve information from the data repositories upon each
      request. This means that information is always up to date and displays the latest
      data sets. The site also provides hyperlinks back to the source information
      hosted at each of the curated databases to facilitate more in-depth analysis of
      the primary data.

PMID- 21075965
TI  - Copper and zinc balance in exercising horses fed 2 forms of mineral supplements.
AB  - Studies comparing the absorption and retention of various forms of trace minerals
      in horses have yielded mixed results. The objective of this study was to compare
      Cu and Zn absorption and retention in exercising horses where the mineral was
      supplemented in the sulfate or organic chelate form. Nine mature horses were used
      in a modified switchback design experiment consisting of seven 28-d periods.
      Horses were fed a diet consisting of 50% concentrate and 50% hay that was
      balanced to meet the energy, protein, Ca, and P requirements for horses
      performing moderate-intensity exercise. Horses were subjected to a controlled
      mineral repletion-depletion diet sequence before feeding the experimental diet to
      standardize mineral status across horses. The experimental diet was designed to
      provide 90% of the 1989 NRC for Cu and Zn, with supplemental mineral provided in
      the inorganic sulfate form (CuSO(4) and ZnSO(4)) or the organic chelate form (Cu
      Lys and Zn-Met). Feed, fecal, urine, and water samples collected during a total
      collection during the last 4 d of the experimental diet periods were analyzed to
      determine apparent absorption and retention of Cu and Zn from the 2 mineral
      forms. A formulation error caused horses receiving the organic chelate diet to
      consume about 3 times the amount of Cu and Zn compared with those fed the sulfate
      supplemented diet. Copper and Zn intake and fecal excretion were greater (P <
      0.05) for horses consuming the organic chelate-supplemented diet. Apparent
      absorption values for all horses were negative. Apparent Cu absorption and
      retention as a percentage of intake were greater for horses fed the organic
      chelate diet (P < 0.05). It is unknown why excretion of Cu and Zn by the horses
      during the total collection exceeded the mineral intake. Although Cu-Lys seemed
      to be better absorbed than CuSO(4) and absorption of Zn-Met and ZnSO(4) were not
      different, these results are tempered by the observation of abnormally high fecal
      and urinary excretion values for Cu and Zn in the present study.

PMID- 21075966
TI  - Artificial long-day photoperiod in the subtropics increases milk production in
      goats giving birth in late autumn.
AB  - Two experiments were conducted to determine whether exposure to a photoperiod of
      artificial long days in autumn increased milk yield in subtropical goats milked
      once (Exp. I) or twice daily (Exp. II). In Exp. I, starting at d 10 of lactation,
      1 group of does was kept under naturally decreasing photoperiod (DD1X; n = 8),
      whereas the other group was submitted to an artificial photoperiod of long days
      (LD1X; n = 8; 16 h light:8 h darkness). The kids were weaned 28 d after
      parturition, and dams were manually milked once daily. Milk yield and milk
      components (fat, protein, and lactose) were assessed up to 140 d of lactation.
      From d 0 to 28 of lactation (suckling phase), mean daily milk yield did not
      differ between DD1X and LD1X goats (2.3 +/- 0.2 kg vs. 2.4 +/- 0.2 kg; P =
      0.717). However, between d 29 and 84 (early milking phase), mean daily milk yield
      was greater in LD1X does than in DD1X does (2.6 +/- 0.1 kg vs. 2.1 +/- 0.1 kg; P
      = 0.001). Finally, between d 85 and 140 (late milking phase), mean daily milk
      yield was greater in LD1X goats than in DD1X goats (P <= 0.05) only during the
      first 2 wk. In Exp. II, one group of goats was exposed to a photoperiod of
      naturally decreasing days (DD2X; n = 8) and another group was submitted to an
      artificial photoperiod of long days (LD2X; n = 7). In both groups, kids were
      weaned on d 28 of lactation and the dams were manually milked twice daily. During
      the nursing phase, mean daily milk yield did not differ between the DD2X and LD2X
      groups (2.5 +/- 0.3 kg vs. 2.6 +/- 0.2 kg; P = 0.767). In the early milking
      phase, mean daily milk yield was greater in LD2X than in DD2X goats (3.3 +/- 0.2
      kg vs. 2.8 +/- 0.2 kg; P = 0.022), whereas during the late milking phase, milk
      yield did not differ between the 2 groups (P = 0.946). In both experiments, milk
      composition was not significantly influenced by exposure to long-day photoperiod.
      We conclude that, in subtropical female goats that start lactation in late
      autumn, exposure to an artificial long-day photoperiod stimulates milk yield,
      even if goats are milked once daily. In addition, combining exposure to long days
      with twice-daily milking will increase further milk yield in such goats without
      affecting milk components.

PMID- 21075967
TI  - Statistical tools to detect genetic variation for a sex dimorphism in piglet
      birth weight.
AB  - Sex differences in birth weight contribute to within-litter variability, which
      itself is connected to piglet survival. Therefore, we studied whether the sex
      difference in piglet birth weight is a genetically variable sex dimorphism. For
      that purpose a linear mixed model including sex-specific additive genetic effects
      was set up. A hypothesis testing problem was defined to detect whether these
      genetic effects significantly differ between sexes. In a second step, the effect
      of sex-linked genes was studied explicitly by partitioning the additive genetic
      effects into autosomal and gonosomal effects. Furthermore, a definition of
      heritability for the sex difference of a randomly chosen pair of littermates with
      opposite sex was given. The proposed models were applied separately to a Landrace
      and Large White data set. Significant genetic variability for the sex dimorphism
      was found in Landrace (P = 0.03) but not in Large White (P = 0.10). Heritability
      estimates were at 3 to 5% depending on the model. The X-chromosomal genetic
      variation was not significant (P > 0.18) at all, whereas the Y-chromosome
      significantly (P < 0.01) contributed to the genetic variation in Landrace with a
      corresponding SD of 34 g. It can be concluded that the sex dimorphism of piglet
      birth weight is genetically variable and a potential target of genetic
      improvement.

PMID- 21075968
TI  - Effect of protein source on nitrogen balance and plasma amino acids in exercising
      horses.
AB  - Plasma AA in horses fed either an all-hay or a hay and grain diet in a
      traditional format have not been investigated. Eight horses were divided into 2
      groups: a hay group fed only grass hay or a hay and a grain group (HG) fed in a
      crossover design for two 5-wk periods. After the first period, horses were fasted
      overnight, followed by feeding with blood sampling every hour for 6 h. A 4-d
      total fecal and urine collection to evaluate N balance followed. A 10-d washout
      period separated the 5-wk feeding periods, during which horses switched diets.
      The second period was also followed by fasting, feeding, blood sampling, and a 4
      d collection period. Horses consumed 840 g of CP in the hay group and 865 g of CP
      in the HG group. Horses in the hay group had a 2.4 +/- 2.4 g/d N balance, which
      was not different from 0 (P = 0.34), whereas horses in the HG group had 5.4 +/-
      2.4 g/d N balance, which was different from 0 (P = 0.045). Fecal N excretion was
      greater for the hay group compared with the HG group (hay = 51.1 +/- 1.3 g/d and
      HG = 45.5 +/- 1.3 g/d; P = 0.011), and urine N excretion was greater for the HG
      group compared with the hay group (hay = 79.3 +/- 2.8 g/d and HG = 89.2 +/- 2.8
      g/d; P = 0.026). Plasma AA concentrations were greater in the HG group compared
      with the hay group for Met (P = 0.001), Lys (P = 0.001), Ile (P = 0.047), Arg (P
      < 0.001), Gln (P = 0.009), and Orn (P = 0.002). Plasma concentrations were less
      for the HG group compared with the hay group for Thr (P < 0.001) and Ala (P <
      0.001). Plasma concentrations of urea were greater for the HG group compared with
      the hay group (P < 0.001), whereas 3-methyl-histidine concentrations were greater
      for the hay group compared with the HG group (P < 0.001). The effect of diet on
      the excretion of N via feces vs. urine in the hay and HG groups is typical. The
      early increases in the plasma concentrations of Met, Val, Ile, Leu, Phe, Lys,
      Arg, and Ala during the postfeeding phase are most likely due to increased
      foregut digestibility as well as a greater quality AA profile in the grain. The
      greater concentrations of Thr, Leu, and Val later in the postfeeding phase for
      the hay group most likely reflects slower digestion because of prolonged
      consumption time compared with the HG group. Improved N balance observed in the
      HG group supports the fact that the HG group had more available AA via the AA
      profile and foregut digestibility of the HG diet. Despite the fact that both
      groups consumed similar amounts of CP, the AA profile and availability affected N
      balance.

PMID- 21075969
TI  - Genetic parameters of product quality and hepatic metabolism in fattened mule
      ducks.
AB  - Genetic parameters of traits related to hepatic lipid metabolism, carcass
      composition, and product quality of overfed mule ducks were estimated on both
      parental lines of this hybrid: the common duck line for the maternal side and the
      Muscovy line for the paternal side. The originality of the statistical model was
      to include simultaneously the additive genetic effect of the common ducks and
      that of the Muscovy ducks, revealing a greater genetic determinism in common than
      in Muscovy. Plasma metabolic indicators (glucose, triglyceride, and cholesterol
      contents) were heritable, in particular at the end of the overfeeding period, and
      heritabilities increased with the overfeeding stage. Carcass composition traits
      were highly heritable in the common line, with values ranging from 0.15 for liver
      weight, 0.21 for carcass weight, and 0.25 for abdominal fat weight to 0.32 for
      breast muscle weight. Heritabilities of technological outputs were greater for
      the fatty liver (0.19 and 0.08, respectively, on common and Muscovy sides for
      liver melting rate) than for the pectoralis major muscle (between 0.02 and 0.05
      on both parental sides for cooking losses). Fortunately, the processing industry
      is mainly facing problems in liver quality, such as too high of a melting rate,
      than in meat quality. The meat quality appraisal criteria (such as texture and
      cooking losses), usually dependent on pH and the rate of decline of pH, were also
      very lowly heritable. This study demonstrated that genetic determinism of meat
      quality and ability of overfeeding is not similar in the common population and in
      the Muscovy population; traits related to fattening, muscle development, and BW
      have heritability values from 2 to 4 times greater on the common line than on the
      Muscovy line, which is relevant for considering different selection strategies.

PMID- 21075970
TI  - Companion animals symposium: microbes and gastrointestinal health of dogs and
      cats.
AB  - Recent molecular studies have revealed complex bacterial, fungal, archaeal, and
      viral communities in the gastrointestinal tract of dogs and cats. More than 10
      bacterial phyla have been identified, with Firmicutes, Bacteroidetes,
      Proteobacteria, Fusobacteria, and Actinobacteria constituting more than 99% of
      all gut microbiota. Microbes act as a defending barrier against invading
      pathogens, aid in digestion, provide nutritional support for enterocytes, and
      play a crucial role in the development of the immune system. Of significance for
      gastrointestinal health is their ability to ferment dietary substrates into short
      chain fatty acids, predominantly to acetate, propionate, and butyrate. However,
      microbes can have also a detrimental effect on host health. Specific pathogens
      (e.g., Salmonella, Campylobacter jejuni, and enterotoxigenic Clostridium
      perfringens) have been implicated in acute and chronic gastrointestinal disease.
      Compositional changes in the small intestinal microbiota, potentially leading to
      changes in intestinal permeability and digestive function, have been suggested in
      canine small intestinal dysbiosis or antibiotic-responsive diarrhea. There is
      mounting evidence that microbes play an important role in the pathogenesis of
      canine and feline inflammatory bowel disease (IBD). Current theories for the
      development of IBD favor a combination of environmental factors, the intestinal
      microbiota, and a genetic susceptibility of the host. Recent studies have
      revealed a genetic susceptibility for defective bacterial clearance in Boxer dogs
      with granulomatous colitis. Differential expression of pathogen recognition
      receptors (i.e., Toll-like receptors) were identified in dogs with chronic
      enteropathies. Similarly to humans, a microbial dysbiosis has been identified in
      feline and canine IBD. Commonly observed microbial changes are increased
      Proteobacteria (i.e., Escherichia coli) with concurrent decreases in Firmicutes,
      especially a reduced diversity in Clostridium clusters XIVa and IV (i.e.,
      Lachnospiraceae, Ruminococcaceae, Faecalibacterium spp.). This would indicate
      that these bacterial groups, important short-chain fatty acid producers, may play
      an important role in promoting intestinal health.

PMID- 21075972
TI  - Clinical impression versus standardized questionnaire: the spinal surgeon's
      ability to assess psychological distress.
AB  - BACKGROUND: Psychological distress can affect spine surgery outcomes. A majority
      of spinal surgeons do not use standardized questionnaires to assess for
      psychological distress and instead rely on their clinical impressions. The
      ability of spinal surgeons to properly assess patients with psychological
      distress has not been adequately evaluated. Our hypothesis was that the clinical
      impressions of spinal surgeons were not as accurate as a standardized
      questionnaire in assessing for psychological distress. METHODS: A prospective
      study was performed with eight physicians, four spinal surgeons and four
      nonoperative spine specialists, who evaluated 400 patients. All patients
      completed the Distress and Risk Assessment Method (DRAM) questionnaire for the
      evaluation of psychological distress. The eight physician subjects, blinded to
      the results of this questionnaire, performed their routine clinical evaluation
      and categorized the patients' psychological distress level. The results of the
      Distress and Risk Assessment Method questionnaire and the surgeons' assessments
      were compared. RESULTS: In the study population of 400 patients, 64% (254 of 400)
      were found to have some level of psychological distress. Twenty-two percent
      (eighty-seven of 400) of the patients were found to have high levels of distress.
      Overall, the physicians' rate of sensitivity when assessing patients with high
      levels of distress was 28.7% (95% confidence interval: 19.5%, 39.4%) with a
      positive predictive value of 47.2% (95% confidence interval: 33.3%, 61.4%).
      Nonoperative spine specialists had a significantly higher sensitivity rate when
      assessing highly distressed patients (41.7% [95% confidence interval: 25.5%,
      59.2%]) than surgeons (19.6% [95% confidence interval: 9.8%, 33.1%]) (p = 0.03).
      The sensitivity rates between experienced (greater than ten years in practice)
      (14.7% [95% confidence interval: 5.0%, 31.1%]) and less experienced (less than
      two years in practice) (29.4% [95% confidence interval: 10.3%, 56.0%]) spinal
      surgeons was not significant (p = 0.27). CONCLUSIONS: A large percentage of
      patients (64%) presenting for spine evaluation have some level of psychological
      distress. When compared with a standardized questionnaire designed to screen for
      psychological distress, spinal surgeons had low sensitivity rates to detect this
      distress. The routine use of a standardized questionnaire to screen for
      psychological distress should be considered.

PMID- 21075971
TI  - The essential role of Epstein-Barr virus in the pathogenesis of multiple
      sclerosis.
AB  - There is increasing evidence that infection with the Epstein-Barr virus (EBV)
      plays a role in the development of multiple sclerosis (MS), a chronic
      inflammatory demyelinating disease of the CNS. This article provides a four-tier
      hypothesis proposing (1) EBV infection is essential for the development of MS;
      (2) EBV causes MS in genetically susceptible individuals by infecting
      autoreactive B cells, which seed the CNS where they produce pathogenic
      autoantibodies and provide costimulatory survival signals to autoreactive T cells
      that would otherwise die in the CNS by apoptosis; (3) the susceptibility to
      develop MS after EBV infection is dependent on a genetically determined
      quantitative deficiency of the cytotoxic CD8+ T cells that normally keep EBV
      infection under tight control; and (4) sunlight and vitamin D protect against MS
      by increasing the number of CD8+ T cells available to control EBV infection. The
      hypothesis makes predictions that can be tested, including the prevention and
      successful treatment of MS by controlling EBV infection.

PMID- 21075973
TI  - Commentary on an article by M.D. Daubs, MD, et al.: "Clinical impression versus
      standardized questionnaire: the spinal surgeon's ability to assess psychological
      distress".

PMID- 21075975
TI  - The utility of in vitro data in making accurate predictions of human P
      glycoprotein-mediated drug-drug interactions: a case study for AZD5672.
AB  - To support drug development and registration, Caco-2 cell monolayer assays have
      previously been set up and validated to determine whether candidate drugs are
      substrates or inhibitors of human P-glycoprotein (P-gp). In this study, the drug
      drug interaction (DDI) potential of N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[4
      methanesulfonylphenyl]propyl}piperidin-4-yl)-N-ethyl-2-[4
      methanesulfonylphenyl]acetamide (AZD5672) was assessed accordingly, and a
      subsequent clinical digoxin interaction study was performed. AZD5672 (1-500 MUM)
      demonstrated concentration-dependent efflux across cell monolayers, which was
      abolished in the presence of ketoconazole and quinidine, identifying AZD5672 as a
      P-gp substrate. In addition, P-gp-mediated digoxin transport was inhibited in a
      concentration-dependent manner by AZD5672 (IC(50) = 32 MUM). Assessment of the
      calculated theoretical gastrointestinal inhibitor concentration ([I(2)]) and
      predicted steady-state maximum total plasma inhibitor concentration ([I(1)])
      indicated the potential for a DDI at the intestinal but not the systemic level
      after the predicted therapeutic dose of AZD5672 (100 mg). A clinical study was
      performed and the plasma pharmacokinetics [observed maximum plasma drug
      concentration (C(max)) and area under the plasma concentration versus time curve
      from 0 to 72 h postdose (AUC(0-72 h))] of orally dosed digoxin (0.5 mg) were
      found to be unaffected by coadministration of AZD5672 (50 mg) at steady state. In
      contrast, a 150-mg dose of AZD5672 significantly increased digoxin C(max) and
      AUC(0-72 h) by 1.82- and 1.33-fold, respectively. Concentration-time profile
      comparisons indicated that digoxin elimination was unchanged by AZD5672, and the
      interaction was most likely to have resulted from inhibition of intestinal P-gp
      leading to increased digoxin absorption. The observed dose-dependent clinically
      significant interaction was accurately predicted using calculated [I(2)] and in
      vitro P-gp inhibition data, confirming AZD5672 to be a P-gp inhibitor in vivo.

PMID- 21075978
TI  - Activity of pyrazinamide in the guinea pig model of tuberculosis.

PMID- 21075976
TI  - Proanthocyanidins inhibit UV-induced immunosuppression through IL-12-dependent
      stimulation of CD8+ effector T cells and inactivation of CD4+ T cells.
AB  - The inhibition of UVB-induced immunosuppression by dietary grape seed
      proanthocyanidins (GSP) has been associated with the induction of interleukin
      (IL)-12 in mice, and we now confirm that GSPs do not inhibit UVB-induced
      immunosuppression in IL-12p40 knockout (IL-12 KO) mice and that treatment of
      these mice with recombinant IL-12 restores the inhibitory effect. To characterize
      the cell population responsible for the GSP-mediated inhibition of UVB-induced
      immunosuppression and the role of IL-12 in this process, we used an adoptive
      transfer approach. Splenocytes and draining lymph nodes were harvested from mice
      that had been administered dietary GSPs (0.5%-1.0%, w/w), exposed to UVB, and
      sensitized by the application of 2,4-dinitrofluorobenzene (DNFB) onto the UVB
      exposed skin. CD8(+) and CD4(+) T cells were positively selected and transferred
      into naive mice that were subsequently challenged by application of DNFB on the
      ear skin. Naive recipients that received CD8(+) T cells from GSP-treated, UVB
      irradiated donors exhibited full contact hypersensitivity (CHS) response. Naive
      mice that received CD4(+) suppressor T cells from GSP-treated, UVB-exposed mice
      could mount a CHS response after sensitization and subsequent challenge with
      DNFB. On culture, the CD8(+) T cells from GSP-treated, UVB-exposed mice secreted
      higher levels (5- to 8-fold) of Th1 cytokines than CD8(+) T cells from UVB
      irradiated mice not treated with GSPs. CD4(+) T cells from GSP-treated, UVB
      exposed mice secreted significantly lower levels (80%-100%) of Th2 cytokines than
      CD4(+) T cells from UVB-exposed mice not treated with GSPs. These data suggest
      that GSPs inhibit UVB-induced immunosuppression by stimulating CD8(+) effector T
      cells and diminishing regulatory CD4(+) T cells.

PMID- 21075979
TI  - Access to primary care from the perspective of Aboriginal patients at an urban
      emergency department.
AB  - In this article, we discuss findings from an ethnographic study in which we
      explored experiences of access to primary care services from the perspective of
      Aboriginal people seeking care at an emergency department (ED) located in a large
      Canadian city. Data were collected over 20 months of immersion in the ED, and
      included participant observation and in-depth interviews with 44 patients triaged
      as stable and nonurgent, most of whom were living in poverty and residing in the
      inner city. Three themes in the findings are discussed: (a) anticipating
      providers' assumptions; (b) seeking help for chronic pain; and (c) use of the ED
      as a reflection of social suffering. Implications of these findings are discussed
      in relation to the role of the ED as well as the broader primary care sector in
      responding to the needs of patients affected by poverty, racialization, and other
      forms of disadvantage.

PMID- 21075980
TI  - Hip fracture prevention strategies in long-term care: a survey of Canadian
      physicians' opinions.
AB  - OBJECTIVE: To garner Canadian physicians' opinions on strategies to reduce hip
      fractures in long-term care (LTC) facilities, focusing on secondary prevention.
      DESIGN: A cross-sectional survey using a mailed, self-administered, written
      questionnaire. SETTING: Canada. PARTICIPANTS: Family physician members of the
      Ontario Long-Term Care Association (n = 165) and all actively practising
      geriatricians registered in the Canadian Medical Directory (n = 81). MAIN OUTCOME
      MEASURES: The strength of recommendations for fracture-reduction strategies in
      LTC and barriers to implementing these strategies. RESULTS: Of the 246 physicians
      sent the questionnaire, 25 declined study materials and were excluded. Of the 221
      remaining, 120 responded for a response rate of 54%. About two-thirds of
      respondents were family physicians (78 of 120) and the rest were mostly
      geriatricians. Most respondents strongly recommended the following secondary
      prevention strategies for use in LTC after hip fracture: calcium, vitamin D, oral
      aminobisphosphonates, physical therapy, and environmental modification (such as
      handrails). Most respondents either did not recommend or recommended limited use
      of etidronate, intravenous bisphosphonates, calcitonin, raloxifene, testosterone
      (for hypogonadal men), and teriparatide. Postmenopausal hormone therapy was
      discouraged or not recommended by most respondents. Support was mixed for the use
      of hip protectors, B vitamins, and folate. Barriers to implementation identified
      by most respondents included a lack of strong evidence of hip fracture reduction
      (for B vitamins and folate, cyclic etidronate, and testosterone), side effects
      (for postmenopausal hormone therapy), poor compliance (for hip protectors), and
      expense (for intravenous bisphosphonates and teriparatide). Some respondents
      cited side effects or poor compliance as barriers to using calcium and potent
      oral bisphosphonates. CONCLUSION: Canadian physicians favour the use of calcium,
      vitamin D, potent oral bisphosphonates, physical therapy, and evironmental
      modifications for LTC residents after hip fracture. Further study at the clinical
      and administrative levels is required to find ways to overcome the specific
      barriers to implementation and effectiveness of these interventions.

PMID- 21075982
TI  - Benzodiazepines: good or bad medicine?

PMID- 21075981
TI  - Barriers to nonpharmacologic treatments for stress, anxiety, and insomnia: family
      physicians' attitudes toward benzodiazepine prescribing.
AB  - OBJECTIVE: To explore the attitudes of FPs toward benzodiazepine (BZD)
      prescribing and the perceived barriers to nonpharmacologic approaches to managing
      stress, anxiety, and insomnia. DESIGN: A questionnaire including 32 statements
      about treatment of insomnia, stress, and anxiety. SETTING: Local quality groups
      for FPs in Belgium. PARTICIPANTS: A total of 948 Belgian FPs. MAIN OUTCOME
      MEASURES: Barriers to using nonpharmacologic approaches in family practice.
      RESULTS: We identified 3 different groups of FPs according to their attitudes
      about BZD prescribing. A first relatively big group of FPs (39%) were not really
      concerned about the risks of BZD prescribing. Those in the second group (17%)
      were aware of the problems associated with BZDs, but did not perceive it to be
      their role to use nonpharmacologic approaches in family practice. Those in the
      third group (44%) were concerned about BZD prescribing and found it to be a "bad
      solution," but were faced with various barriers to applying nonpharmacologic
      approaches. Surprisingly, we found that nearly 97% of FPs thought that most
      people were eligible for nonpharmacologic approaches, but experienced
      implementation barriers at the level of the patient, the level of the FP, and the
      level of the health care system. CONCLUSION: Using different education and
      behavioural-change strategies for different FP groups seems important. A large
      group of FPs does not find prescribing BZDs to be problematic. Sensitizing and
      alerting FPs to this issue remains very important.

PMID- 21075984
TI  - Challenges and achievements in caring for the elderly.

PMID- 21075986
TI  - Editorial fellowships in family medicine.

PMID- 21075987
TI  - Missed opportunities.

PMID- 21075988
TI  - Complex issues.

PMID- 21075989
TI  - Bone lead measurement.

PMID- 21075990
TI  - Office management of urinary incontinence among older patients.
AB  - OBJECTIVE: To provide family physicians with a guide to office management of
      urinary incontinence (UI) among older patients. SOURCES OF INFORMATION: Ovid
      MEDLINE and the Cochrane database were searched using the terms urinary
      incontinence, stress incontinence, overactive bladder, urge incontinence,
      elderly, and geriatrics. MAIN MESSAGE: A variety of conditions affecting the
      nervous system and the lower urinary tract can affect bladder function and UI.
      Among older patients the effects of decreased cognition and impaired mobility can
      be substantial, and environmental barriers can play a role. When managing older
      patients with UI, emphasis on treating concurrent conditions, optimizing
      medications, and working on lifestyle and behavioural factors is at least as
      important as pharmacologic treatment. Medications are relevant, but the potential
      for adverse effects increases among older patients. CONCLUSION: Various resources
      are available to support family physicians in office management of UI, and family
      physicians can improve symptoms and the quality of patients' lives by screening
      for and helping patients to manage incontinence.

PMID- 21075991
TI  - Approach to assessing fitness to drive in patients with cardiac and cognitive
      conditions.
AB  - OBJECTIVE: To help physicians become more comfortable assessing the fitness to
      drive of patients with complex cardiac and cognitive conditions. QUALITY OF
      EVIDENCE: The approach described is based on the authors' clinical practices,
      recommendations from the Third Canadian Consensus Conference on Diagnosis and
      Treatment of Dementia, and guidelines from the 2003 Canadian Cardiovascular
      Society Consensus Conference. MAIN MESSAGE: When assessing fitness to drive in
      patients with multiple, complex health problems, physicians should divide
      conditions that might affect driving into acute intermittent (ie, not usually
      present on examination) and chronic persistent (ie, always present on
      examination) medical conditions. Physicians should address acute intermittent
      conditions first, to allow time for recovery from chronic persistent features
      that might be reversible. Decisions regarding fitness to drive in acute
      intermittent disorders are based on probability of recurrence; decisions in
      chronic persistent disorders are based on functional assessment. CONCLUSION:
      Assessing fitness to drive is challenging at the best of times. When patients
      have multiple comorbidities, assessment becomes even more difficult. This article
      provides clinicians with systematic approaches to work through such complex
      cases.

PMID- 21075992
TI  - Perinatal exposure to maternal lamotrigine: clinical considerations for the
      mother and child.
AB  - QUESTION: The question of neonatal safety during breastfeeding when mothers are
      taking lamotrigine (LTG) has become more prevalent in my practice. There are some
      theoretical concerns about breastfeeding while taking LTG, which have been
      compounded by a published case report of toxicity in the breastfed neonate of a
      mother taking LTG. How should I advise my patients who wish to breastfeed while
      taking LTG? ANSWER: Most neonates born to mothers taking LTG have already been
      exposed to the drug for 9 months in utero, given the chronic indications for
      which the drug is intended. Lamotrigine exposure via breast milk is considerably
      less than placental transfer, with serum LTG concentrations in neonates higher at
      birth than during lactation. While a single case of toxicity has been reported in
      a neonate exposed to LTG via breast milk, in most circumstances, breastfeeding
      can be initiated and maintained given the tremendous benefits of mothers' milk.
      On the other hand, toxicity during breastfeeding might occur more commonly in the
      mother, if sufficient and gradual dose readjustments are not undertaken in the
      weeks following delivery.

PMID- 21075993
TI  - Influenza vaccination for children with asthma.
AB  - QUESTION: Parents of children with asthma are encouraged by many health
      organizations to vaccinate their children against seasonal influenza viruses. Is
      the influenza vaccine efficient in preventing asthma exacerbation? Are current
      vaccinations safe to administer to children with asthma? ANSWER: Infection with
      influenza viruses can cause substantial respiratory morbidity in children with
      underlying chronic disease such as asthma. Although vaccination against influenza
      does not reduce or shorten asthma exacerbations, the intramuscular trivalent
      vaccine is safe and has a beneficial effect on the quality of life of children
      with asthma.

PMID- 21075994
TI  - Treating hypertension in the very elderly.

PMID- 21075995
TI  - Drug-related taste disturbance: a contributing factor in geriatric syndromes.

PMID- 21075996
TI  - Ophthaproblem. Can you identify this condition? Benign essential blepharospasm.

PMID- 21075997
TI  - Dermacase. Can you identify this condition? Superficial basal cell carcinoma.

PMID- 21075998
TI  - Treating nonseptic olecranon bursitis: a 3-step technique.

PMID- 21075999
TI  - Correlates of a "do not hospitalize" designation: in a sample of frail nursing
      home residents in Vancouver.
AB  - OBJECTIVE: To explore what nursing home resident demographic, clinical,
      functional, and health services utilization characteristics influence a "do not
      hospitalize" designation. DESIGN: Historical cohort study. SETTING: Vancouver,
      BC. PARTICIPANTS: Extended care residents in 2 hospital-based and 4 free-standing
      nursing homes who died between 2001 and 2007. MAIN OUTCOME MEASURES: The
      designation of "do not hospitalize" on a resident's chart. RESULTS: Continuity of
      family physician care from admission to death (adjusted hazard ratio [AHR] 2.16,
      95% confidence interval [CI] 1.33 to 3.49), a sudden and unexpected death (AHR
      0.43, 95% CI 0.25 to 0.73), and age (AHR 1.02, 95% CI 1.01 to 1.02) were
      independently associated with a "do not hospitalize" designation. CONCLUSION: The
      greater than 2-fold positive association of continuity of family physician care
      with a "do not hospitalize" designation is an interesting addition to the
      literature on how continuity of physician care matters.

PMID- 21076000
TI  - Integrating Physician Services in the Home: evaluation of an innovative program.
AB  - OBJECTIVE: To evaluate a new program, Integrating Physician Services in the Home
      (IPSITH), to integrate family practice and home care for acutely ill patients.
      DESIGN: Causal model, mixed-method, multi-measures design including comparison of
      IPSITH and non-IPSITH patients. Data were collected through chart reviews and
      through surveys of IPSITH and non-IPSITH patients, caregivers, family physicians,
      and community nurses. SETTING: London, Ont, and surrounding communities, where
      home care is coordinated through the Community Care Access Centre. PARTICIPANTS:
      A total of 82 patients receiving the new IPSITH program of care (including 29
      family physicians and 1 nurse practitioner), 82 non-randomized matched patients
      receiving usual care (and their physicians), community nurses, and caregivers.
      MAIN OUTCOME MEASURES: Emergency department (ED) visits and satisfaction with
      care. Analysis included a process evaluation of the IPSITH program and an
      outcomes evaluation comparing IPSITH and non-IPSITH patients. RESULTS: Patients
      and family physicians were very satisfied with the addition of a nurse
      practitioner to the IPSITH team. Controlling for symptom severity, a
      significantly smaller proportion of IPSITH patients had ED visits (3.7% versus
      20.7%; P = .002), and IPSITH patients and their caregivers, family physicians,
      and community nurses had significantly higher levels of satisfaction (P < .05).
      There was no difference in caregiver burden between groups. CONCLUSION: Family
      physicians can be integrated into acute home care when appropriately supported by
      a team including a nurse practitioner. This integrated team was associated with
      better patient and system outcomes. The gains for the health system are reduced
      strain on hospital EDs and more satisfied patients.

PMID- 21076001
TI  - Supporting primary health care nurse practitioners' transition to practice.
AB  - OBJECTIVE: To examine role transition and support requirements for nurse
      practitioner (NP) graduates in their first year of practice from the perspectives
      of the NPs and coparticipants familiar with the NPs' practices; and to make
      recommendations for practice, education, and policy. DESIGN: Descriptive
      qualitative design informed by focused ethnography and narrative analysis using
      semistructured, in-depth, qualitative interviews. SETTING: Primary health care
      (PHC) settings in Ontario in which NPs worked. PARTICIPANTS: Twenty-three NPs who
      had graduated from the Ontario Primary Health Care Nurse Practitioner program,
      and 21 coparticipants including family physicians, NPs, and managers who were
      familiar with the NPs' practices. METHODS: Anglophone and francophone NPs in
      their first year of practice in PHC settings were contacted by e-mail or letter.
      Participating NPs nominated colleagues in the workplace who could comment on
      their practice. Interviews were conducted within the first 3 months, at 6 months,
      and at 12 months of the NPs' first year of practice and were transcribed verbatim
      and coded. Job descriptions and organizational charts demonstrating the NPs'
      organization positions were also analyzed. The researchers collaboratively
      analyzed the interviews using a systematic data analysis protocol. MAIN FINDINGS:
      Familiarity of colleagues and employers with the NP role and scope of practice
      was an important element in successful NP role transition. Lack of preparation
      for integrating NPs into clinical settings and lack of infrastructure,
      orientation, mentorship, and awareness of the NP role and needs made the
      transition difficult for many. One-third of the NPs had changed employment,
      identifying interprofessional conflict or problems with acceptance of their role
      in new practice environments as reasons for the change. CONCLUSION: The
      transition of NP graduates in Ontario was complicated by the health care
      environment being ill-prepared to receive them owing to rapid changes in PHC.
      Strategies for mentorship and for the integration of new NPs into PHC settings
      are available and need to be implemented by health professionals and
      administrators. Recommendations for family physicians to support NP graduate
      transition into practice are provided.

PMID- 21076002
TI  - Driving and cognitive decline: a need for collaboration.

PMID- 21076007
TI  - Deconvolution of chromatin immunoprecipitation-microarray (ChIP-chip) analysis of
      MBF occupancies reveals the temporal recruitment of Rep2 at the MBF target genes.
AB  - MBF (or DSC1) is known to regulate transcription of a set of G(1)/S-phase genes
      encoding proteins involved in regulation of DNA replication. Previous studies
      have shown that MBF binds not only the promoter of G(1)/S-phase genes, but also
      the constitutive genes; however, it was unclear if the MBF bindings at the G(1)/S
      phase and constitutive genes were mechanistically distinguishable. Here, we
      report a chromatin immunoprecipitation-microarray (ChIP-chip) analysis of MBF
      binding in the Schizosaccharomyces pombe genome using high-resolution genome
      tiling microarrays. ChIP-chip analysis indicates that the majority of the MBF
      occupancies are located at the intragenic regions. Deconvolution analysis using
      Rpb1 ChIP-chip results distinguishes the Cdc10 bindings at the Rpb1-poor loci
      (promoters) from those at the Rpb1-rich loci (intragenic sequences). Importantly,
      Res1 binding at the Rpb1-poor loci, but not at the Rpb1-rich loci, is dependent
      on the Cdc10 function, suggesting a distinct binding mechanism. Most Cdc10
      promoter bindings at the Rpb1-poor loci are associated with the G(1)/S-phase
      genes. While Res1 or Res2 is found at both the Cdc10 promoter and intragenic
      binding sites, Rep2 appears to be absent at the Cdc10 promoter binding sites but
      present at the intragenic sites. Time course ChIP-chip analysis demonstrates that
      Rep2 is temporally accumulated at the coding region of the MBF target genes,
      resembling the RNAP-II occupancies. Taken together, our results show that
      deconvolution analysis of Cdc10 occupancies refines the functional subset of
      genomic binding sites. We propose that the MBF activator Rep2 plays a role in
      mediating the cell cycle-specific transcription through the recruitment of RNAP
      II to the MBF-bound G(1)/S-phase genes.

PMID- 21076008
TI  - The C-module-binding factor supports amplification of TRE5-A retrotransposons in
      the Dictyostelium discoideum genome.
AB  - Retrotransposable elements are molecular parasites that have invaded the genomes
      of virtually all organisms. Although retrotransposons encode essential proteins
      to mediate their amplification, they also require assistance by host cell-encoded
      machineries that perform functions such as DNA transcription and repair. The
      retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a
      notable amount of both sense and antisense RNAs, which are generated from element
      internal promoters, located in the A module and the C module, respectively. We
      observed that TRE5-A retrotransposons depend on the C-module-binding factor
      (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA
      supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal
      domain of CbfA was found to be required and sufficient to mediate the
      accumulation of TRE5-A transcripts, but it did not support productive
      retrotransposition of TRE5-A. This result suggests different roles for CbfA
      protein domains in the regulation of TRE5-A retrotransposition frequency in D.
      discoideum cells. Although CbfA binds to the C module in vitro, the factor
      regulates neither C-module nor A-module promoter activity in vivo. We speculate
      that CbfA supports the amplification of TRE5-A retrotransposons by suppressing
      the expression of an as yet unidentified component of the cellular
      posttranscriptional gene silencing machinery.

PMID- 21076009
TI  - The N-terminal domain of the Flo1 flocculation protein from Saccharomyces
      cerevisiae binds specifically to mannose carbohydrates.
AB  - Saccharomyces cerevisiae cells possess a remarkable capacity to adhere to other
      yeast cells, which is called flocculation. Flocculation is defined as the
      phenomenon wherein yeast cells adhere in clumps and sediment rapidly from the
      medium in which they are suspended. These cell-cell interactions are mediated by
      a class of specific cell wall proteins, called flocculins, that stick out of the
      cell walls of flocculent cells. The N-terminal part of the three-domain protein
      is responsible for carbohydrate binding. We studied the N-terminal domain of the
      Flo1 protein (N-Flo1p), which is the most important flocculin responsible for
      flocculation of yeast cells. It was shown that this domain is both O and N
      glycosylated and is structurally composed mainly of beta-sheets. The binding of N
      Flo1p to D-mannose, alpha-methyl-D-mannoside, various dimannoses, and mannan
      confirmed that the N-terminal domain of Flo1p is indeed responsible for the sugar
      binding activity of the protein. Moreover, fluorescence spectroscopy data suggest
      that N-Flo1p contains two mannose carbohydrate binding sites with different
      affinities. The carbohydrate dissociation constants show that the affinity of N
      Flo1p for mono- and dimannoses is in the millimolar range for the binding site
      with low affinity and in the micromolar range for the binding site with high
      affinity. The high-affinity binding site has a higher affinity for low-molecular
      weight (low-MW) mannose carbohydrates and no affinity for mannan. However, mannan
      as well as low-MW mannose carbohydrates can bind to the low-affinity binding
      site. These results extend the cellular flocculation model on the molecular
      level.

PMID- 21076010
TI  - Type 2C protein phosphatases in fungi.
AB  - Type 2C Ser/Thr phosphatases are a remarkable class of protein phosphatases,
      which are conserved in eukaryotes and involved in a large variety of functional
      processes. Unlike in other Ser/Thr phosphatases, the catalytic polypeptide is not
      usually associated with regulatory subunits, and functional specificity is
      achieved by encoding multiple isoforms. For fungi, most information comes from
      the study of type 2C protein phosphatase (PP2C) enzymes in Saccharomyces
      cerevisiae, where seven PP2C-encoding genes (PTC1 to -7) with diverse functions
      can be found. More recently, data on several Candida albicans PP2C proteins
      became available, suggesting that some of them can be involved in virulence. In
      this work we review the available literature on fungal PP2Cs and explore sequence
      databases to provide a comprehensive overview of these enzymes in fungi.

PMID- 21076011
TI  - Comparative genomics and the evolution of pathogenicity in human pathogenic
      fungi.
AB  - Because most fungi have evolved to be free-living in the environment and because
      the infections they cause are usually opportunistic in nature, it is often
      difficult to identify specific traits that contribute to fungal pathogenesis. In
      recent years, there has been a surge in the number of sequenced genomes of human
      fungal pathogens, and comparison of these sequences has proved to be an excellent
      resource for exploring commonalities and differences in how these species
      interact with their hosts. In order to survive in the human body, fungi must be
      able to adapt to new nutrient sources and environmental stresses. Therefore,
      genes involved in carbohydrate and amino acid metabolism and transport and genes
      encoding secondary metabolites tend to be overrepresented in pathogenic species
      (e.g., Aspergillus fumigatus). However, it is clear that human commensal yeast
      species such as Candida albicans have also evolved a range of specific factors
      that facilitate direct interaction with host tissues. The evolution of virulence
      across the human pathogenic fungi has occurred largely through very similar
      mechanisms. One of the most important mechanisms is gene duplication and the
      expansion of gene families, particularly in subtelomeric regions. Unlike the case
      for prokaryotic pathogens, horizontal transfer of genes between species and other
      genera does not seem to have played a significant role in the evolution of fungal
      virulence. New sequencing technologies promise the prospect of even greater
      numbers of genome sequences, facilitating the sequencing of multiple genomes and
      transcriptomes within individual species, and will undoubtedly contribute to a
      deeper insight into fungal pathogenesis.

PMID- 21076012
TI  - Mountain biking-related injuries treated in emergency departments in the United
      States, 1994-2007.
AB  - BACKGROUND: Injury research on mountain biking has been mostly limited to
      examining professional riders and off-road biking. Mountain bikes represent the
      largest segment of bike sales in the United States. Recreational mountain bike
      use is popular and understudied. PURPOSE: To describe the scope, distribution,
      and trends of mountain bike-related injuries treated in US emergency departments.
      STUDY DESIGN: Descriptive epidemiologic study. METHODS: A retrospective analysis
      was conducted with data from the National Electronic Injury Surveillance System
      of the US Consumer Product Safety Commission for patients aged >= 8 years from
      1994 through 2007. Sample weights provided by the system were used to calculate
      national estimates of mountain bike-related injuries based on 4624 cases.
      Bivariate comparisons between categorical variables were assessed with injury
      proportion ratios and 95% confidence intervals. RESULTS: Nationwide, an estimated
      217 433 patients were treated for mountain bike-related injuries in US emergency
      departments from 1994 to 2007, an average of 15 531 injuries per year. The annual
      number of injuries decreased 56%, from a high of 23 177 in 1995 to 10 267 in 2007
      (P < .001). The most common injuries were upper extremity fractures (10.6%) and
      shoulder fractures (8.3%). Patients aged 14 to 19 years sustained a greater
      proportion of traumatic brain injuries (8.4%) than did patients aged 8 to 13
      years and >= 20 years combined (4.3%). A greater proportion of female riders
      (6.1%) than male riders (4.5%) were hospitalized. CONCLUSION: Mountain bike
      related injuries decreased from 1994 to 2007. Upper extremity fractures were the
      most common injury. Girls and women may be more likely than boys and men to
      sustain more severe injuries requiring hospitalization. Despite the decline over
      the past decade, more can be done to improve safety and reduce injuries in this
      popular recreational activity.

PMID- 21076013
TI  - Biomechanical evaluation of 3 arthroscopic self-cinching stitches for shoulder
      arthroscopy: the lasso-loop, lasso-mattress, and double-cinch stitches.
AB  - BACKGROUND: The tissue-suture interface remains the most common site of failure
      in rotator cuff repairs. Improving stitch strengths may lead to lower failure
      rates. PURPOSE: To compare biomechanical properties of 3 self-cinching stitches
      to the simple, mattress, modified Mason-Allen, and massive cuff stitches. STUDY
      DESIGN: Controlled laboratory study. METHODS: In sum, 336 sheep infraspinatus
      tendon grafts were randomized among 7 stitches. Each graft was cyclically loaded
      on a mechanical testing system from 5 to 30 N for 20 cycles and then loaded to
      failure. A mixed-effect multivariate regression model was used to test
      significance of suture type on cyclic elongation, peak-to-peak displacement, and
      ultimate load. Estimated means and standard deviations are reported from the
      regression model. RESULTS: Ultimate load for the simple stitch was significantly
      lower than for the other stitches. The lasso-loop and mattress stitch
      demonstrated similar ultimate loads. The double-cinch had a higher ultimate load
      than the lasso-loop or mattress stitch, although it was significantly weaker than
      the modified Mason-Allen, lasso-mattress, and massive cuff. The lasso-mattress
      had a superior ultimate load to the modified Mason-Allen and a similar ultimate
      load to the massive cuff stitch. One significant difference was found in cyclic
      elongation (1.42 mm for the simple to 1.80 mm for the double-cinch), and the
      cinching mechanism accounted for 0.2-mm higher elongation. CONCLUSION: Self
      cinching stitches lead to superior tissue-holding strength at the tissue-suture
      interface when compared with equivalent non-self-cinching stitches. Self-cinching
      stitches have greater elongation values. How these differences in cyclic
      elongation clinically influence gap formation at the repair site is unknown. The
      greater displacement seen in the self-cinching stitches is a potential concern
      because minimal gap formation is desired for a strong repair. CLINICAL RELEVANCE:
      The lasso-loop stitch is a stronger alternative to a simple stitch, and the
      double-cinch and lasso-mattress stitches are stronger alternatives to a mattress
      stitch.

PMID- 21076014
TI  - Prevalence and associated factors of Osgood-Schlatter syndrome in a population
      based sample of Brazilian adolescents.
AB  - BACKGROUND: Osgood-Schlatter (OS) syndrome is a disease of the musculoskeletal
      system often observed during the bone growth phase in adolescents. HYPOTHESIS/
      PURPOSE: Demographic and anthropometric factors and those linked to the practice
      of sports may be related to the prevalence of OS. The aim of the present study
      was to describe the epidemiologic profile and associated factors of individuals
      with OS syndrome in a population-based sample of Brazilian adolescents. STUDY
      DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A cross-sectional
      study was conducted with 956 adolescent students (474 boys, 482 girls) from 2008
      to 2009 enrolled in the school system of Natal, Brazil. The age ranged between 12
      and 15 years (13.7 +/- 1.04 years). Tests were performed to assess the
      anthropometric and clinical aspects related to OS. To confirm the diagnosis of OS
      syndrome, the participant had to fulfill all the following clinical criteria:
      pain with direct pressure on the tibial apophysis; aforementioned pain before,
      during, and after physical activities; enlargement or prominence of the tibial
      apophysis; pain with resisted knee extension; and pain from jumping. RESULTS: The
      prevalence of OS in the sample was 9.8% (11.0% of boys and 8.3% of girls; boys,
      13.5 +/- 1.07 years; girls, 13.6 +/- 1.01 years). The results showed that 74.6%
      of the students suffered from muscle shortening. Multivariate analysis using
      logistic regression showed that the factors associated with the presence of OS
      were the regular practice of sport activity (odds ratio, 1.94; 95% confidence
      interval, 1.22-3.10) and the shortening of the rectus femoris muscle (odds ratio,
      7.15; 95% confidence interval, 2.86-17.86). CONCLUSIONS: The regular practice of
      sports in the pubertal phase and the shortening of the rectus femoris muscle were
      the main factors associated to the presence of OS syndrome in the students.

PMID- 21076016
TI  - Evaluation of transtibial double-bundle posterior cruciate ligament
      reconstruction using a single-sling method with a tibialis anterior allograft.
AB  - BACKGROUND: The authors devised a double-bundle posterior cruciate ligament
      reconstruction technique in combination with a single-sling method. However, the
      double-bundle technique needs more simplicity and a decreased possibility of
      failure. HYPOTHESIS: A novel surgical technique of transtibial double-bundle
      posterior cruciate ligament reconstruction using a single-sling method with a
      tibialis anterior allograft, previously introduced, produces satisfactory
      results. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-one
      patients who underwent double-bundle transtibial isolated posterior cruciate
      ligament reconstruction using a single-sling method between July 2003 and
      September 2007 were enrolled in this study. The exclusion criteria applied were
      (1) a multiligamentous injury, (2) posterior cruciate ligament reconstruction
      previously performed using another technique, and (3) the presence of any
      additional injury capable of affecting knee stability. The Lysholm and
      International Knee Documentation Committee (IKDC) knee scales were used for the
      clinical outcome evaluation. Stability was evaluated using a KT-2000 arthrometer.
      The evaluation was performed by comparing preoperative and last follow-up
      results. RESULTS: Nineteen men and 2 women were enrolled, with a mean follow-up
      of 49.2 months (range, 25-73 months). The mean Lysholm score was 53 +/- 5.3
      (range, 34-68) preoperatively and improved to 83.5 +/- 13 (range, 61-97) at the
      last follow-up after surgery (P < .001). The IKDC score also improved from
      preoperative (0 A, 0 B, 7 C, 14 D) to final follow-up (8 A, 9 B, 3 C, 1 D; P <
      .001). Mean side-to-side difference in posterior translation, measured using the
      KT-2000 arthrometer, was 13.5 +/- 1.2 mm preoperatively and 3.4 +/- 0.8 mm at
      last follow-up evaluations (mean 51.7 months postoperatively). CONCLUSION: After
      follow-up for longer than 24 months, the transtibial double-bundle posterior
      cruciate ligament reconstruction with a single sling was found to produce
      satisfactory clinical and stability results, which indicates that the described
      technique should be viewed as a viable alternative.

PMID- 21076015
TI  - Patellar maltracking correlates with vastus medialis activation delay in
      patellofemoral pain patients.
AB  - BACKGROUND: Delayed onset of vastus medialis (VM) activity compared with vastus
      lateralis activity is a reported cause for patellofemoral pain. The delayed onset
      of VM activity in patellofemoral pain patients likely causes an imbalance in
      muscle forces and lateral maltracking of the patella; however, evidence relating
      VM activation delay to patellar maltracking is sparse. The aim of this study was
      to investigate the relationship between VM activation delay and patellar
      maltracking measures in pain-free controls and patellofemoral pain patients.
      HYPOTHESIS: Patellar tilt and bisect offset, measures of patellar tracking,
      correlate with VM activation delay in patellofemoral pain patients classified as
      maltrackers. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS:
      Vasti muscle activations were recorded in pain-free (n = 15) and patellofemoral
      pain (n = 40) participants during walking and jogging. All participants were
      scanned in an open-configuration magnetic resonance scanner in an upright
      weightbearing position to acquire the position of the patella with respect to the
      femur. Patellar tilt and bisect offset were measured, and patellofemoral pain
      participants were classified into normal tracking and maltracking groups.
      RESULTS: Correlations between VM activation delay and patellar maltracking
      measures were statistically significant in only the patellofemoral pain
      participants classified as maltrackers with both abnormal tilt and abnormal
      bisect offset (R(2) = .89, P < .001, with patellar tilt during walking; R(2) =
      .75, P = .012, with bisect offset during jogging). There were no differences
      between the means of activation delays in pain-free and all patellofemoral pain
      participants during walking (P = .516) or jogging (P = .731). CONCLUSION: There
      was a relationship between VM activation delay and patellar maltracking in the
      subgroup of patellofemoral pain participants classified as maltrackers with both
      abnormal tilt and abnormal bisect offset. CLINICAL RELEVANCE: A clinical
      intervention such as VM retraining may be effective in only a subset of
      patellofemoral pain participants-namely, those with excessive tilt and excessive
      bisect offset measures. The results highlight the importance of appropriate
      classification of patellofemoral pain patients before selection of a clinical
      intervention.

PMID- 21076018
TI  - Alcohol exposure during late gestation adversely affects myocardial development
      with implications for postnatal cardiac function.
AB  - Prenatal exposure to high levels of ethanol is associated with cardiac
      malformations, but the effects of lower levels of exposure on the heart are
      unclear. Our aim was to investigate the effects of daily exposure to ethanol
      during late gestation, when cardiomyocytes are undergoing maturation, on the
      developing myocardium. Pregnant ewes were infused with either ethanol (0.75 g/kg)
      or saline for 1 h each day from gestational days 95 to 133 (term ~145 days);
      tissues were collected at 134 days. In sheep, cardiomyocytes mature during late
      gestation as in humans. Within the left ventricle (LV), cardiomyocyte number was
      determined using unbiased stereology and cardiomyocyte size and nuclearity
      determined using confocal microscopy. Collagen deposition was quantified using
      image analysis. Genes relating to cardiomyocyte proliferation and apoptosis were
      examined using quantitative real-time PCR. Fetal plasma ethanol concentration
      reached 0.11 g/dL after EtOH infusions. Ethanol exposure induced significant
      increases in relative heart weight, relative LV wall volume, and cardiomyocyte
      cross-sectional area. Ethanol exposure advanced LV maturation in that the
      proportion of binucleated cardiomyocytes increased by 12%, and the number of
      mononucleated cardiomyocytes was decreased by a similar amount. Apoptotic gene
      expression increased in the ethanol-exposed hearts, although there were no
      significant differences between groups in total cardiomyocyte number or
      interstitial collagen. Daily exposure to a moderate dose of ethanol in late
      gestation accelerates the maturation of cardiomyocytes and increases
      cardiomyocyte and LV tissue volume in the fetal heart. These effects on
      cardiomyocyte growth may program for long-term cardiac vulnerability.

PMID- 21076017
TI  - Cardiovascular responses elicited by a new endogenous angiotensin in the nucleus
      tractus solitarius of the rat.
AB  - Cardiovascular effects of angiotensin-(1-12) [ANG-(1-12)] were studied in the
      medial nucleus of the tractus solitarius (mNTS) in anesthetized, artificially
      ventilated, adult male Wistar rats. Microinjections (100 nl) of ANG-(1-12) (0.06
      mM) into the mNTS elicited maximum decreases in mean arterial pressure (MAP; 34
      +/- 5.8 mmHg) and heart rate (HR; 39 +/- 3.7 beats/min). Bilateral vagotomy
      abolished ANG-(1-12)-induced bradycardia. Efferent greater splanchnic nerve
      activity was decreased by microinjections of ANG-(1-12) into the mNTS. Blockade
      of ANG type 1 receptors (AT(1)Rs; using ZD-7155 or L-158,809), but not ANG type 2
      receptors (AT(2)Rs; using PD-123319), significantly attenuated ANG-(1-12)-induced
      cardiovascular responses. Simultaneous inhibition of both angiotensin-converting
      enzyme (ACE; using captopril) and chymase (using chymostatin) completely blocked
      the effects of ANG-(1-12). Microinjections of A-779 [ANG-(1-7) antagonist] did
      not attenuate ANG-(1-12)-induced responses. Pressure ejection of ANG-(1-12) (0.06
      mM, 2 nl) caused excitation of barosensitive mNTS neurons, which was blocked by
      prior application of the AT(1)R antagonist. ANG-(1-12)-induced excitation of mNTS
      neurons was also blocked by prior sequential applications of captopril and
      chymostatin. These results indicate that 1) microinjections of ANG-(1-12) into
      the mNTS elicited depressor and bradycardic responses by exciting barosensitive
      mNTS neurons; 2) the decreases in MAP and HR were mediated via sympathetic and
      vagus nerves, respectively; 3) AT(1)Rs, but not AT(2)Rs, mediated these actions
      of ANG-(1-12); 4) the responses were mediated via the conversion of ANG-(1-12) to
      ANG II and both ACE and chymase were involved in this conversion; and 5) ANG-(1
      7) was not one of the metabolites of ANG-(1-12) in the mNTS.

PMID- 21076019
TI  - Respiration drives phase synchronization between blood pressure and RR interval
      following loss of cardiovagal baroreflex during vasovagal syncope.
AB  - Loss of the cardiovagal baroreflex (CVB), thoracic hypovolemia, and hyperpnea
      contribute to the nonlinear time-dependent hemodynamic instability of vasovagal
      syncope. We used a nonlinear phase synchronization index (PhSI) to describe the
      extent of coupling between cardiorespiratory parameters, systolic blood pressure
      (SBP) or arterial pressure (AP), RR interval (RR), and ventilation, and a
      directional index (DI) measuring the direction of coupling. We also examined
      phase differences directly. We hypothesized that AP-RR interval PhSI would be
      normal during early upright tilt, indicating intact CVB, but would progressively
      decrease as faint approached and CVB failed. Continuous measurements of AP, RR
      interval, respiratory plethysomography, and end-tidal CO2 were recorded supine
      and during 70-degree head-up tilt in 15 control subjects and 15 fainters. Data
      were evaluated during five distinct times: baseline, early tilt, late tilt,
      faint, and recovery. During late tilt to faint, fainters exhibited a biphasic
      change in SBP-RR interval PhSI. Initially in fainters during late tilt, SBP-RR
      interval PhSI decreased (fainters, from 0.65+/-0.04 to 0.24+/-0.03 vs. control
      subjects, from 0.51+/-0.03 to 0.48+/-0.03; P<0.01) but then increased at the time
      of faint (fainters=0.80+/-0.03 vs. control subjects=0.42+/-0.04; P<0.001)
      coinciding with a change in phase difference from positive to negative. Starting
      in late tilt and continuing through faint, fainters exhibited increasing phase
      coupling between respiration and AP PhSI (fainters=0.54+/-0.06 vs. control
      subjects=0.27+/-0.03; P<0.001) and between respiration and RR interval
      (fainters=0.54+/-0.05 vs. control subjects=0.37+/-0.04; P<0.01). DI indicated
      respiratory driven AP (fainters=0.84+/-0.04 vs. control subjects=0.39+/-0.09;
      P<0.01) and RR interval (fainters=0.73+/-0.10 vs. control subjects=0.23+/-0.11;
      P<0.001) in fainters. The initial drop in the SBP-RR interval PhSI and
      directional change of phase difference at late tilt indicates loss of cardiovagal
      baroreflex. The subsequent increase in SBP-RR interval PhSI is due to a
      respiratory synchronization and drive on both AP and RR interval. Cardiovagal
      baroreflex is lost before syncope and supplanted by respiratory reflexes,
      producing hypotension and bradycardia.

PMID- 21076020
TI  - Sprouty2 downregulates angiogenesis during mouse skin wound healing.
AB  - Angiogenesis is regulated by signals received by receptor tyrosine kinases such
      as vascular endothelial growth factor receptors. Mammalian Sprouty (Spry)
      proteins are known to function by specifically antagonizing the activation of the
      mitogen-activated protein kinase signaling pathway by receptor tyrosine kinases,
      a pathway known to promote angiogenesis. To examine the role of Spry2 in the
      regulation of angiogenesis during wound repair, we used a model of murine dermal
      wound healing. Full-thickness excisional wounds (3 mm) were made on the dorsum of
      anesthetized adult female FVB mice. Samples were harvested at multiple time
      points postwounding and analyzed using real-time RT-PCR, Western blot analysis,
      and immunofluorescent histochemistry. Spry2 mRNA and protein levels in the wound
      bed increased significantly during the resolving phases of healing, coincident
      with the onset of vascular regression in this wound model. In another experiment,
      intracellular levels of Spry2 or its dominant-negative mutant (Y55F) were
      elevated by a topical application to the wounds of controlled-release gel
      containing cell permeable, transactivator of transcription-tagged Spry2,
      Spry2Y55F, or green fluorescent protein (as control). Wound samples were analyzed
      for vascularity using CD31 immunofluorescent histochemistry as well as for total
      and phospho-Erk1/2 protein content. The treatment of wounds with Spry2 resulted
      in a significant decrease in vascularity and a reduced abundance of phospho
      Erk1/2 compared with wounds treated with the green fluorescent protein control.
      In contrast, the wounds treated with the dominant-negative Spry2Y55F exhibited a
      moderate increase in vascularity and elevated phospho-Erk1/2 content. These
      results indicate that endogenous Spry2 functions to downregulate angiogenesis in
      the healing murine skin wound, potentially by inhibiting the mitogen-activated
      protein kinase signaling pathway.

PMID- 21076021
TI  - Calcium and zinc dyshomeostasis during isoproterenol-induced acute stressor
      state.
AB  - Acute hyperadrenergic stressor states are accompanied by cation dyshomeostasis,
      together with the release of cardiac troponins predictive of necrosis. The signal
      transducer-effector pathway accounting for this pathophysiological scenario
      remains unclear. We hypothesized that a dyshomeostasis of extra- and
      intracellular Ca2+ and Zn2+ occurs in rats in response to isoproterenol (Isop)
      including excessive intracellular Ca2+ accumulation (EICA) and mitochondrial
      [Ca2+]m-induced oxidative stress. Contemporaneously, the selective translocation
      of Ca2+ and Zn2+ to tissues contributes to their fallen plasma levels. Rats
      received a single subcutaneous injection of Isop (1 mg/kg body wt). Other groups
      of rats received pretreatment for 10 days with either carvedilol (C), a beta
      adrenergic receptor antagonist with mitochondrial Ca2+ uniporter-inhibiting
      properties, or quercetin (Q), a flavonoid with mitochondrial-targeted antioxidant
      properties, before Isop. We monitored temporal responses in the following: [Ca2+]
      and [Zn2+] in plasma, left ventricular (LV) apex, equator and base, skeletal
      muscle, liver, spleen, and peripheral blood mononuclear cells (PBMC), indices of
      oxidative stress and antioxidant defenses, mitochondrial permeability transition
      pore (mPTP) opening, and myocardial fibrosis. We found ionized hypocalcemia and
      hypozincemia attributable to their tissue translocation and also a heterogeneous
      distribution of these cations among tissues with a preferential Ca2+ accumulation
      in the LV apex, muscle, and PBMC, whereas Zn2+ declined except in liver, where it
      increased corresponding with upregulation of metallothionein, a Zn2+-binding
      protein. EICA was associated with a simultaneous increase in tissue 8-isoprostane
      and increased [Ca2+]m accompanied by a rise in H2O2 generation, mPTP opening, and
      scarring, each of which were prevented by either C or Q. Thus excessive [Ca2+]m,
      coupled with the induction of oxidative stress and increased mPTP opening,
      suggests that this signal-transducer-effector pathway is responsible for Isop
      induced cardiomyocyte necrosis at the LV apex.

PMID- 21076022
TI  - The thermodynamics of diastole: kinematic modeling-based derivation of the P-V
      loop to transmitral flow energy relation with in vivo validation.
AB  - Pressure-volume (P-V) loop-based analysis facilitates thermodynamic assessment of
      left ventricular function in terms of work and energy. Typically these quantities
      are calculated for a cardiac cycle using the entire P-V loop, although
      thermodynamic analysis may be applied to a selected phase of the cardiac cycle,
      specifically, diastole. Diastolic function is routinely quantified by analysis of
      transmitral Doppler E-wave contours. The first law of thermodynamics requires
      that energy (epsilon) computed from the Doppler E-wave (epsilonE-wave) and the
      same portion of the P-V loop (epsilonP-V E-wave) be equivalent. These energies
      have not been previously derived nor have their predicted equivalence been
      experimentally validated. To test the hypothesis that epsilonP-V E-wave and
      epsilonE-wave are equivalent, we used a validated kinematic model of filling to
      derive epsilonE-wave in terms of chamber stiffness, relaxation/viscoelasticity,
      and load. For validation, simultaneous (conductance catheter) P-V and
      echocadiographic data from 12 subjects (205 total cardiac cycles) having a range
      of diastolic function were analyzed. For each E-wave, epsilonE-wave was compared
      with epsilonP-V E-wave calculated from simultaneous P-V data. Linear regression
      yielded the following: epsilonP-V E-wave=alphaepsilonE-wave+b (R2=0.67), where
      alpha=0.95 and b=6e(-5). We conclude that E-wave-derived energy for suction
      initiated early rapid filling epsilonE-wave, quantitated via kinematic modeling,
      is equivalent to invasive P-V-defined filling energy. Hence, the thermodynamics
      of diastole via epsilonE-wave generate a novel mechanism-based index of diastolic
      function suitable for in vivo phenotypic characterization.

PMID- 21076024
TI  - Transient receptor potential A1 channel contributes to activation of the muscle
      reflex.
AB  - This study was undertaken to elucidate the role played by transient receptor
      potential A1 channels (TRPA1) in activating the muscle reflex, a
      sympathoexcitatory drive originating in contracting muscle. First, we tested the
      hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly
      increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate,
      a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle
      circulation. This led to a 33% increase in renal sympathetic nerve activity
      (RSNA). The effect of allyl isothiocyanate was a reflex because the response was
      prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that
      blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous
      static contraction of the hindlimb muscles, induced by electrical stimulation of
      the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood
      pressure. The integrated RSNA during contraction was reduced by HC-030031, a
      TRPA1 antagonist, injected intra-arterially (163 +/- 24 vs. 95 +/- 21 arbitrary
      units, before vs. after HC-030031, P < 0.05). Third, we attempted to identify
      potential endogenous stimulants of TRPA1, responsible for activating the muscle
      reflex. Increases in RSNA in response to injection into the muscle circulation of
      arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by
      products of contraction and stimulants of muscle afferents during contraction,
      were reduced by HC-030031. These observations suggest that the TRPA1 located on
      muscle afferents is part of the muscle reflex and further support the notion that
      arachidonic acid metabolites, bradykinin, and diprotonated phosphate are
      candidates for endogenous agonists of TRPA1.

PMID- 21076023
TI  - Cigarette smoking impairs Na+-K+-ATPase activity in the human coronary
      microcirculation.
AB  - The extracellular K(+) concentration ([K(+)](o)) has been proposed to link
      cardiac metabolism with coronary perfusion and arrhythmogenesis, particularly
      during ischemia. Several animal studies have also supported K(+) as an EDHF that
      activates Na(+)-K(+)-ATPase and/or inwardly rectifying K(+) (K(ir)) channels.
      Therefore, we examined the vascular reactivity of human coronary arterioles
      (HCAs) to small elevations in [K(+)](o), the influence of risk factors for
      coronary disease, and the role of K(+) as an EDHF. Changes in the internal
      diameter of HCAs were recorded with videomicroscopy. Most vessels dilated to
      increases in [K(+)](o) with a maximal dilation of 55 +/- 6% primarily at 12.5
      20.0 mM KCl (n = 38, average: 16 +/- 1 mM). Ouabain, a Na(+)-K(+)-ATPase
      inhibitor, alone reduced the dilation, and the addition of Ba(2+), a K(ir)
      channel blocker, abolished the remaining dilation, whereas neither endothelial
      denudation nor Ba(2+) alone reduced the dilation. Multivariate analysis revealed
      that cigarette smoking was the only risk factor associated with impaired dilation
      to K(+). Ouabain significantly reduced the vasodilation in HCAs from subjects
      without cigarette smoking but not in those with smoking. Cigarette smoking
      downregulated the expression of the Na(+)-K(+)-ATPase catalytic alpha(1)-subunit
      but not Kir2.1 in the vessels. Ouabain abolished the dilation in endothelium
      denuded vessels to a same extent to that with the combination of ouabain and
      Ba(2+) in endothelium-intact vessels, whereas neither ouabain nor ouabain plus
      Ba(2+) reduced EDHF-mediated dilations to bradykinin and ADP. A rise in [K(+)](o)
      dilates HCAs primarily via the activation of Na(+)-K(+)-ATPase in vascular smooth
      muscle cells with a considerable contribution of K(ir) channels in the
      endothelium, indicating that [K(+)](o) may modify coronary microvascular
      resistance in humans. Na(+)-K(+)-ATPase activity is impaired in subjects who
      smoke, possibly contributing to dysregulation of the coronary microcirculation,
      excess ischemia, and arrhythmogenesis in those subjects. K(+) does not likely
      serve as an EDHF in the human coronary arteriolar dilation to bradykinin and ADP.

PMID- 21076025
TI  - Increased propensity for cell death in diabetic human heart is mediated by
      mitochondrial-dependent pathways.
AB  - Progressive energy deficiency and loss of cardiomyocyte numbers are two prominent
      factors that lead to heart failure in experimental models. Signals that mediate
      cardiomyocyte cell death have been suggested to come from both extrinsic (e.g.,
      cytokines) and intrinsic (e.g., mitochondria) sources, but the evidence
      supporting these mechanisms remains unclear, and virtually nonexistent in humans.
      In this study, we investigated the sensitivity of the mitochondrial permeability
      transition pore (mPTP) to calcium (Ca(2+)) using permeabilized myofibers of right
      atrium obtained from diabetic (n = 9) and nondiabetic (n = 12) patients with
      coronary artery disease undergoing nonemergent coronary revascularization
      surgery. Under conditions that mimic the energetic state of the heart in vivo
      (pyruvate, glutamate, malate, and 100 MUM ADP), cardiac mitochondria from
      diabetic patients show an increased sensitivity to Ca(2+)-induced mPTP opening
      compared with nondiabetic patients. This increased mPTP Ca(2+) sensitivity in
      diabetic heart mitochondria is accompanied by a substantially greater rate of
      mitochondrial H(2)O(2) emission under identical conditions, despite no
      differences in respiratory capacity under these conditions or mitochondrial
      enzyme content. Activity of the intrinsic apoptosis pathway mediator caspase-9
      was greater in diabetic atrial tissue, whereas activity of the extrinsic pathway
      mediator caspase-8 was unchanged between groups. Furthermore, caspase-3 activity
      was not significantly increased in diabetic atrial tissue. These data
      collectively suggest that the myocardium in diabetic patients has a greater
      overall propensity for mitochondrial-dependent cell death, possibly as a result
      of metabolic stress-imposed changes that have occurred within the mitochondria,
      rendering them more susceptible to insults such as Ca(2+) overload. In addition,
      they lend further support to the notion that mitochondria represent a viable
      target for future therapies directed at ameliorating heart failure and other
      comorbidities that come with diabetes.

PMID- 21076027
TI  - Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic
      and hemodynamic deficiencies.
AB  - Cardiac dysfunction is a common cause of death among pediatric patients with
      mutations in the lysosomal hydrolase alpha-l-iduronidase (IDUA) gene, which
      causes mucopolysaccharidosis type I (MPS-I). The purpose of this study was to
      analyze adrenergic regulation of cardiac hemodynamic function in MPS-I. An
      analysis of murine heart function was performed using conductance micromanometry
      to assess in vivo cardiac hemodynamics. Although MPS-I (IDUA(-/-)) mice were able
      to maintain normal cardiac output and ejection fraction at baseline, this cohort
      had significantly compromised systolic and diastolic function compared with
      IDUA(+/-) control mice. During dobutamine infusion MPS-I mice did not
      significantly increase cardiac output from baseline, indicative of blunted
      cardiac reserve. Autonomic tone, measured functionally by beta-blockade,
      indicated that MPS-I mice required catecholaminergic stimulation to maintain
      baseline hemodynamics. Survival analysis showed mortality only among MPS-I mice.
      Linear regression analysis revealed that heightened end-systolic volume in the
      resting heart is significantly correlated with susceptibility to mortality in MPS
      I hearts. This study reveals that cardiac remodeling in the pathology of MPS-I
      involves heightened adrenergic tone at the expense of cardiac reserve with
      cardiac decompensation predicted on the basis of increased baseline systolic
      volumes.

PMID- 21076026
TI  - Y1767C, a novel SCN5A mutation, induces a persistent Na+ current and potentiates
      ranolazine inhibition of Nav1.5 channels.
AB  - Long QT syndrome type 3 (LQT3) has been traced to mutations of the cardiac Na(+)
      channel (Na(v)1.5) that produce persistent Na(+) currents leading to delayed
      ventricular repolarization and torsades de pointes. We performed mutational
      analyses of patients suffering from LQTS and characterized the biophysical
      properties of the mutations that we uncovered. One LQT3 patient carried a
      mutation in the SCN5A gene in which the cysteine was substituted for a highly
      conserved tyrosine (Y1767C) located near the cytoplasmic entrance of the Na(v)1.5
      channel pore. The wild-type and mutant channels were transiently expressed in
      tsA201 cells, and Na(+) currents were recorded using the patch-clamp technique.
      The Y1767C channel produced a persistent Na(+) current, more rapid inactivation,
      faster recovery from inactivation, and an increased window current. The
      persistent Na(+) current of the Y1767C channel was blocked by ranolazine but not
      by many class I antiarrhythmic drugs. The incomplete inactivation, along with the
      persistent activation of Na(+) channels caused by an overlap of voltage-dependent
      activation and inactivation, known as window currents, appeared to contribute to
      the LQTS phenotype in this patient. The blocking effect of ranolazine on the
      persistent Na(+) current suggested that ranolazine may be an effective
      therapeutic treatment for patients with this mutation. Our data also revealed the
      unique role for the Y1767 residue in inactivating and forming the intracellular
      pore of the Na(v)1.5 channel.

PMID- 21076028
TI  - Dorsal root tetrodotoxin-resistant sodium channels do not contribute to the
      augmented exercise pressor reflex in rats with chronic femoral artery occlusion.
AB  - We investigated the contribution of tetrodotoxin (TTX)-resistant sodium channels
      to the augmented exercise pressor reflex observed in decerebrated rats with
      femoral artery ligation. The pressor responses to static contraction, to tendon
      stretch, and to electrical stimulation of the tibial nerve were compared before
      and after blocking TTX-sensitive sodium channels on the L3-L6 dorsal roots of
      rats whose hindlimbs were freely perfused and rats whose femoral arteries were
      ligated 72 h before the start of the experiment. In the freely perfused group
      (n=9), pressor (Delta22+/-4 mmHg) and cardioaccelerator (Delta32+/-6 beats/min)
      responses to contraction were attenuated by 1 MUM TTX (Delta4+/-1 mmHg, P<0.05
      and Delta17+/-4 beats/min, P<0.05, respectively). In the 72 h ligated group
      (n=9), the augmented pressor response to contraction (32+/-4 mmHg) was also
      attenuated by 1 MUM TTX (Delta8+/-2 mmHg, P<0.05). The cardioaccelerator response
      to contraction was not significantly attenuated in these rats. In addition, TTX
      suppressed the pressor response to tendon stretch in both groups of rats.
      Electrical stimulation of the tibial nerve evoked similar pressor responses
      between the two groups (freely perfused: Delta74+/-9 mmHg and 72 h ligated:
      Delta78+/-5 mmHg). TTX attenuated the pressor response to the tibial nerve
      stimulation by about one-half in both groups. Application of the TTX-resistant
      sodium channel blocker A-803467 (1 MUM) with TTX (1 MUM) did not block the
      pressor response to tibial nerve stimulation to any greater extent than did
      application of TTX (1 MUM) alone. Although the contribution of TTX-resistant
      sodium channels to the augmented exercise pressor reflex may be slightly
      increased in rats with chronic femoral artery ligation, TTX-resistant sodium
      channels on dorsal roots do not play a major role in the augmented exercise
      pressor reflex.

PMID- 21076030
TI  - The spread of innovations in social networks.
AB  - Which network structures favor the rapid spread of new ideas, behaviors, or
      technologies? This question has been studied extensively using epidemic models.
      Here we consider a complementary point of view and consider scenarios where the
      individuals' behavior is the result of a strategic choice among competing
      alternatives. In particular, we study models that are based on the dynamics of
      coordination games. Classical results in game theory studying this model provide
      a simple condition for a new action or innovation to become widespread in the
      network. The present paper characterizes the rate of convergence as a function of
      the structure of the interaction network. The resulting predictions differ
      strongly from the ones provided by epidemic models. In particular, it appears
      that innovation spreads much more slowly on well-connected network structures
      dominated by long-range links than in low-dimensional ones dominated, for
      example, by geographic proximity.

PMID- 21076029
TI  - Assessment of endothelial function of large, medium, and small vessels: a unified
      myograph.
AB  - Endothelial dysfunction precedes the development of morphological atherosclerotic
      changes and can also contribute to lesion development in cardiovascular diseases.
      Currently, there is a lack of a single method to determine endothelial function
      of the entire range of vessel dimensions from aorta to arterioles. Here we
      assessed endothelial function of a large range of size arteries using a unified
      isovolumic myograph method. The method maintains a constant volume of fluid in
      the lumen of the vessel during contraction and relaxation, which are
      characterized by an increase and a decrease of pressure, respectively. Segments
      of six aortas, six common femoral arteries, and six mesenteric arteries from
      rats; six carotid arteries from mice; and six coronary and carotid arteries from
      pigs were used. The endothelium-dependent dose-response vasorelaxation was
      determined with endothelium-dependent vasodilators while arterial preconstriction
      was induced with vasoconstrictors at a submaximal dose. The circumferential
      midtension during vascular reactivity varied from 43.1 +/- 7.9 to 2.59 +/- 0.46
      mN/mm (from large to small arteries), whereas the circumferential midstress
      showed a much smaller variation from 217 +/- 23.5 to 123 +/- 15.3 kPa (in the
      same range of vessels). We also found that overinflation and axial overelongation
      compromised endothelium-dependent vasorelaxation to underscore the significance
      of vessel preload. In conclusion, an isovolumic myograph was used to unify
      arterial vasoreactivity from large to small arteries and shows the uniformity of
      wall stress and %tension throughout the range of vessel sizes.

PMID- 21076031
TI  - Synchronized Northern Hemisphere climate change and solar magnetic cycles during
      the Maunder Minimum.
AB  - The Maunder Minimum (A.D. 1645-1715) is a useful period to investigate possible
      sun-climate linkages as sunspots became exceedingly rare and the characteristics
      of solar cycles were different from those of today. Here, we report annual
      variations in the oxygen isotopic composition (delta(18)O) of tree-ring cellulose
      in central Japan during the Maunder Minimum. We were able to explore possible sun
      climate connections through high-temporal resolution solar activity (radiocarbon
      contents; Delta(14)C) and climate (delta(18)O) isotope records derived from
      annual tree rings. The tree-ring delta(18)O record in Japan shows distinct
      negative delta(18)O spikes (wetter rainy seasons) coinciding with rapid cooling
      in Greenland and with decreases in Northern Hemisphere mean temperature at around
      minima of decadal solar cycles. We have determined that the climate signals in
      all three records strongly correlate with changes in the polarity of solar dipole
      magnetic field, suggesting a causal link to galactic cosmic rays (GCRs). These
      findings are further supported by a comparison between the interannual patterns
      of tree-ring delta(18)O record and the GCR flux reconstructed by an ice-core
      (10)Be record. Therefore, the variation of GCR flux associated with the
      multidecadal cycles of solar magnetic field seem to be causally related to the
      significant and widespread climate changes at least during the Maunder Minimum.

PMID- 21076032
TI  - Mechanism of replication blocking and bypass of Y-family polymerase {eta} by
      bulky acetylaminofluorene DNA adducts.
AB  - Heterocyclic aromatic amines produce bulky C8 guanine lesions in vivo, which
      interfere and disrupt DNA and RNA synthesis. These lesions are consequently
      strong replication blocks. In addition bulky adducts give rise to point and
      frameshift mutations. The translesion synthesis (TLS) DNA polymerase eta is able
      to bypass slowly C8 bulky adduct lesions such as the widely studied 2
      aminofluorene-dG and its acetylated analogue mainly in an error-free manner.
      Replicative polymerases are in contrast fully blocked by the acetylated lesion.
      Here, we show that TLS efficiency of Pol eta depends critically on the size of
      the bulky adduct forming the lesion. Based on the crystal structure, we show why
      the bypass reaction is so difficult and we provide a model for the bypass
      reaction. In our model, TLS is accomplished without rotation of the lesion into
      the anti conformation as previously thought.

PMID- 21076033
TI  - A naturally chimeric type IIA topoisomerase in Aquifex aeolicus highlights an
      evolutionary path for the emergence of functional paralogs.
AB  - Bacteria frequently possess two type IIA DNA topoisomerases, gyrase and topo IV,
      which maintain chromosome topology by variously supercoiling, relaxing, and
      disentangling DNA. DNA recognition and functional output is thought to be
      controlled by the C-terminal domain (CTD) of the topoisomerase DNA binding
      subunit (GyrA/ParC). The deeply rooted organism Aquifex aeolicus encodes one type
      IIA topoisomerase conflictingly categorized as either DNA gyrase or topo IV. To
      resolve this enzyme's catalytic properties and heritage, we conducted a series of
      structural and biochemical studies on the isolated GyrA/ParC CTD and the
      holoenzyme. Whereas the CTD displays a global structure similar to that seen in
      bone fide GyrA and ParC paralogs, it lacks a key functional motif (the "GyrA
      box") and fails to wrap DNA. Biochemical assays show that the A. aeolicus
      topoisomerase cannot supercoil DNA, but robustly removes supercoils and
      decatenates DNA, two hallmark activities of topo IV. Despite these properties,
      phylogenetic analyses place all functional domains except the CTD squarely within
      a gyrase lineage, and the A. aeolicus GyrB subunit is capable of supporting
      supercoiling with Escherichia coli GyrA, but not DNA relaxation with E. coli
      ParC. Moreover, swapping the A. aeolicus GyrA/ParC CTD with the GyrA CTD from
      Thermotoga maritima creates an enzyme that negatively supercoils DNA. These
      findings identify A. aeolicus as the first bacterial species yet found to exist
      without a functional gyrase, and suggest an evolutionary path for generation of
      bacterial type IIA paralogs.

PMID- 21076034
TI  - Detoxifying carcinogenic polyhalogenated quinones by hydroxamic acids via an
      unusual double Lossen rearrangement mechanism.
AB  - Hydroxamic acids, which are best-known for their metal-chelating properties in
      biomedical research, have been found to effectively detoxify the carcinogenic
      polyhalogenated quinoid metabolites of pentachlorophenol and other persistent
      organic pollutants. However, the chemical mechanism underlying such detoxication
      is unclear. Here we show that benzohydroxamic acid (BHA) could dramatically
      accelerate the conversion of the highly toxic tetrachloro-1, 4-benzoquinone (p
      chloranil) to the much less toxic 2,5-dichloro-3, 6-dihydroxy-1, 4-benzoquonine
      (chloranilic acid), with rate accelerations of up to 150,000-fold. In contrast,
      no enhancing effect was observed with O-methyl BHA. The major reaction product of
      BHA was isolated and identified as O-phenylcarbamyl benzohydroxamate. On the
      basis of these data and oxygen-18 isotope-labeling studies, we proposed that
      suicidal nucleophilic attack coupled with an unexpected double Lossen
      rearrangement reaction was responsible for this remarkable acceleration of the
      detoxication reaction. This is the first report of an unusually mild and facile
      Lossen-type rearrangement, which could take place under normal physiological
      conditions in two consecutive steps. Our findings may have broad biological and
      environmental implications for future research on hydroxamic acids and
      polyhalogenated quinoid carcinogens, which are two important classes of compounds
      of major biomedical and environmental interest.

PMID- 21076035
TI  - Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and
      virus transmission.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell
      leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-1-associated
      myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and
      by extracellular viral assemblies. Here, we uncovered an additional mechanism of
      virus transmission that is regulated by the HTLV-1-encoded p8 protein. We found
      that the p8 protein, known to anergize T cells, is also able to increase T-cell
      contact through lymphocyte function-associated antigen-1 clustering. In addition,
      p8 augments the number and length of cellular conduits among T cells and is
      transferred to neighboring T cells through these conduits. p8, by establishing a
      T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the
      ability of p8 to simultaneously anergize and cluster T cells, together with its
      induction of cellular conduits, secures virus propagation while avoiding the
      host's immune surveillance. This work identifies p8 as a viral target for the
      development of therapeutic strategies that may limit the expansion of infected
      cells in HTLV-1 carriers and decrease HTLV-1-associated morbidity.

PMID- 21076036
TI  - Flexible mechanisms underlie the evaluation of visual confidence.
AB  - Visual processing is fraught with uncertainty: The visual system must attempt to
      estimate physical properties despite missing information and noisy mechanisms.
      Sometimes high visual uncertainty translates into lack of confidence in our
      visual perception: We are aware of not seeing well. The mechanism by which we
      achieve this awareness--how we assess our own visual uncertainty--is unknown, but
      its investigation is critical to our understanding of visual decision mechanisms.
      The simplest possibility is that the visual system relies on cues to uncertainty,
      stimulus features usually associated with visual uncertainty, like blurriness.
      Probabilistic models of the brain suggest a more sophisticated mechanism, in
      which visual uncertainty is explicitly represented as probability distributions.
      In two separate experiments, observers performed a visual discrimination task in
      which confidence could be determined by the cues available (contrast and crowding
      or eccentricity and masking) or by their actual performance, the latter requiring
      a more sophisticated mechanism than cue monitoring. Results show that observers'
      confidence followed performance rather than cues, indicating that the mechanisms
      underlying the evaluation of visual confidence are relatively complex. This
      result supports probabilistic models, which imply the existence of sophisticated
      mechanisms for evaluating uncertainty.

PMID- 21076037
TI  - Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and
      modifies amyloid pathology in an Alzheimer mouse model.
AB  - Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein receptor
      that regulates cholesterol efflux from the peripheral tissues to the liver. SR-BI
      has been identified on astrocytes and vascular smooth muscle cells in Alzheimer's
      disease brain and has been shown to mediate adhesion of microglia to fibrillar
      amyloid-beta (Abeta). Here we report that SR-BI mediates perivascular macrophage
      response and regulates Abeta-related pathology and cerebral amyloid angiopathy in
      an Alzheimer's mouse model. Reduction or deletion of SR-BI gene in heterozygous
      or homozygous deficient mice (SR-BI(+/-), (-/-)) resulted in a significant
      increase in perivascular macrophages in the brain. SR-BI deletion had no effect
      on apolipoprotein E or apolipoprotein AI levels in the mouse brain. Our analysis
      revealed increased levels of SR-BI expression in the brains of human amyloid
      precursor protein (Swedish, Indiana) transgenic mice (J20 line). To evaluate the
      role of SR-BI in Alzheimer's disease pathogenesis, we inactivated one SR-BI
      allele in J20 transgenic mice. SR-BI reduction in J20/SR-BI(+/-) mice enhanced
      fibrillar amyloid deposition and cerebral amyloid angiopathy and also exacerbated
      learning and memory deficits compared with J20 littermates. Immunohistochemical
      analysis revealed localization of SR-BI on perivascular macrophages in tight
      association with Abeta deposits. Our data suggest that SR-BI reduction impairs
      the response of perivascular macrophages to Abeta and enhances the Abeta-related
      phenotype and cerebral amyloid angiopathy in J20 mice. These results reveal that
      SR-BI, a scavenger receptor primarily involved in high-density lipoprotein
      cholesterol transport, plays an essential role in Alzheimer's disease and
      cerebral amyloid angiopathy.

PMID- 21076039
TI  - Participation of the p38 pathway in Drosophila host defense against pathogenic
      bacteria and fungi.
AB  - The signaling network of innate immunity in Drosophila is constructed by multiple
      evolutionarily conserved pathways, including the Toll- or Imd-regulated NF-kappaB
      and JNK pathways. The p38 MAPK pathway is evolutionarily conserved in stress
      responses, but its role in Drosophila host defense is not fully understood. Here
      we show that the p38 pathway also participates in Drosophila host defense. In
      comparison with wild-type flies, the sensitivity to microbial infection was
      slightly higher in the p38a mutant, significantly higher in the p38b mutant, but
      unchanged in the p38c mutant. The p38b;p38a double-mutant flies were
      hypersensitive to septic injury. The immunodeficiency of p38b;p38a mutant flies
      was also demonstrated by hindgut melanization and larvae stage lethality that
      were induced by microbes naturally presented in fly food. A canonical MAP3K-MKK
      cascade was found to mediate p38 activation in response to infection in flies.
      However, neither Toll nor Imd was required for microbe-induced p38 activation. We
      found that p38-activated heat-shock factor and suppressed JNK collectively
      contributed to host defense against infection. Together, our data demonstrate
      that the p38 pathway-mediated stress response contribute to Drosophila host
      defense against microbial infection.

PMID- 21076041
TI  - Syntaxin clusters assemble reversibly at sites of secretory granules in live
      cells.
AB  - Syntaxin resides in the plasma membrane, where it helps to catalyze membrane
      fusion during exocytosis. The protein also forms clusters in cell-free and
      granule-free plasma-membrane sheets. We imaged the interaction between syntaxin
      and single secretory granules by two-color total internal reflection microscopy
      in PC12 cells. Syntaxin-GFP assembled in clusters at sites where single granules
      had docked at the plasma membrane. Clusters were intermittently present at
      granule sites, as syntaxin molecules assembled and disassembled in a coordinated
      fashion. Recruitment to granules required the N-terminal domain of syntaxin, but
      not the entry of syntaxin into SNARE complexes. Clusters facilitated exocytosis
      and disassembled once exocytosis was complete. Syntaxin cluster formation defines
      an intermediate step in exocytosis.

PMID- 21076040
TI  - Single secretory granules of live cells recruit syntaxin-1 and synaptosomal
      associated protein 25 (SNAP-25) in large copy numbers.
AB  - Before secretory vesicles undergo exocytosis, they must recruit the proteins
      syntaxin-1 and synaptosomal associated protein 25 (SNAP-25) in the plasma
      membrane. GFP-labeled versions of both proteins cluster at sites where secretory
      granules have docked. Single-particle tracking shows that minority populations of
      both molecules are strongly hindered in their mobility, consistent with their
      confinement in nanodomains. We measured the fluorescence of granule-associated
      clusters, the fluorescence of single molecules, and the numbers of unlabeled
      syntaxin-1 and SNAP-25 molecules per cell. There was a more than 10-fold excess
      of SNAP-25 over syntaxin-1. Fifty to seventy copies each of syntaxin-1 and SNAP
      25 molecules were associated with a single docked granule, many more than have
      been reported to be required for fusion.

PMID- 21076043
TI  - Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo.
AB  - Hepcidin is a major regulator of iron homeostasis, and its expression in liver is
      regulated by iron, inflammation, and erythropoietic activity with mechanisms that
      involve bone morphogenetic proteins (BMPs) binding their receptors and
      coreceptors. Here we show that exogenous heparin strongly inhibited hepcidin
      expression in hepatic HepG2 cells at pharmacologic concentrations, with a
      mechanism that probably involves bone morphogenetic protein 6 sequestering and
      the blocking of SMAD signaling. Treatment of mice with pharmacologic doses of
      heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation,
      reduced spleen iron concentration, and increased serum iron. Moreover, we
      observed a strong reduction of serum hepcidin in 5 patients treated with heparin
      to prevent deep vein thrombosis, which was accompanied by an increase of serum
      iron and a reduction of C-reactive protein levels. The data show an unrecognized
      role for heparin in regulating iron homeostasis and indicate novel approaches to
      the treatment of iron-restricted iron deficiency anemia.

PMID- 21076044
TI  - Pharmacologic modulation of the calcium-sensing receptor enhances hematopoietic
      stem cell lodgment in the adult bone marrow.
AB  - The ability of hematopoietic stem cells (HSCs) to undergo self-renewal is partly
      regulated by external signals originating from the stem cell niche. Our previous
      studies with HSCs obtained from fetal liver of mice deficient for the calcium
      sensing receptor (CaR) have shown the crucial role of this receptor in HSC
      lodgment and engraftment in the bone marrow (BM) endosteal niche. Using a CaR
      agonist, Cinacalcet, we assessed the effects of stimulating the CaR on the
      function of murine HSCs. Our results show that CaR stimulation increases
      primitive hematopoietic cell activity in vitro, including growth in stromal cell
      cocultures, adhesion to extracellular matrix molecules such as collagen I and
      fibronectin, and migration toward the chemotactic stimulus, stromal cell-derived
      factor 1alpha. Receptor stimulation also led to augmented in vivo homing, CXCR4
      mediated lodgment at the endosteal niche, and engraftment capabilities. These
      mechanisms by which stimulating the CaR dictates preferential localization of
      HSCs in the BM endosteal niche provide additional insights into the fundamental
      interrelationship between the stem cell and its niche. These studies also have
      implications in the area of clinical stem cell transplantation, where ex vivo
      modulation of the CaR may be envisioned as a strategy to enhance HSC engraftment
      in the BM.

PMID- 21076045
TI  - Structure of the leukemia oncogene LMO2: implications for the assembly of a
      hematopoietic transcription factor complex.
AB  - The LIM only protein 2 (LMO2) is a key regulator of hematopoietic stem cell
      development whose ectopic expression in T cells leads to the onset of acute
      lymphoblastic leukemia. Through its LIM domains, LMO2 is thought to function as
      the scaffold for a DNA-binding transcription regulator complex, including the
      basic helix-loop-helix proteins SCL/TAL1 and E47, the zinc finger protein GATA-1,
      and LIM-domain interacting protein LDB1. To understand the role of LMO2 in the
      formation of this complex and ultimately to dissect its function in normal and
      aberrant hematopoiesis, we solved the crystal structure of LMO2 in complex with
      the LID domain of LDB1 at 2.4 A resolution. We observe a largely unstructured
      LMO2 kept in register by the LID binding both LIM domains. Comparison of
      independently determined crystal structures of LMO2 reveals large movements
      around a conserved hinge between the LIM domains. We demonstrate that such
      conformational flexibility is necessary for binding of LMO2 to its partner
      protein SCL/TAL1 in vitro and for the function of this complex in vivo. These
      results, together with molecular docking and analysis of evolutionarily conserved
      residues, yield the first structural model of the DNA-binding complex containing
      LMO2, LDB1, SCL/TAL1, and GATA-1.

PMID- 21076046
TI  - Mesenchymal stem cells express serine protease inhibitor to evade the host immune
      response.
AB  - Clinical trials using mesenchymal stem cells (MSCs) have been initiated
      worldwide. An improved understanding of the mechanisms by which allogeneic MSCs
      evade host immune responses is paramount to regulating their survival after
      administration. This study has focused on the novel role of serine protease
      inhibitor (SPI) in the escape of MSCs from host immunosurveillance through the
      inhibition of granzyme B (GrB). Our data indicate bone marrow-derived murine MSCs
      express SPI6 constitutively. MSCs from mice deficient for SPI6 (SPI6(-/-))
      exhibited a 4-fold higher death rate by primed allogeneic cytotoxic T cells than
      did wild-type MSCs. A GrB inhibitor rescued SPI6(-/-) MSCs from cytotoxic T-cell
      killing. Transduction of wild-type MSCs with MigR1-SPI6 also protected MSCs from
      cytotoxic T cell-mediated death in vitro. In addition, SPI6(-/-) MSCs displayed a
      shorter lifespan than wild-type MSCs when injected into an allogeneic host. We
      conclude that SPI6 protects MSCs from GrB-mediated killing and plays a pivotal
      role in their survival in vivo. Our data could serve as a basis for future SPI
      based strategies to regulate the survival and function of MSCs after
      administration and to enhance the efficacy of MSC-based therapy for diseases.

PMID- 21076047
TI  - Loss of PTEN permits CXCR4-mediated tumorigenesis through ERK1/2 in prostate
      cancer cells.
AB  - Loss of PTEN is frequently observed in androgen-independent prostate cancer,
      resulting in the deregulation of metastatic events. SDF1alpha activation of CXCR4
      induces signaling pathways that have been implicated in prostate metastasis and
      progression to an advanced disease. The pathways of CXCR4 and PTEN converge,
      leading to the promotion and regulation of tumorigenesis, respectively. However,
      loss of PTEN may permit CXCR4 to progress prostate cancer to an advanced disease.
      In the present study, we investigated the involvement of PTEN in CXCR4-mediated
      tumorigenesis. When screening advanced metastatic prostate cancer cell lines for
      PTEN, we observed a loss of expression in PC3 and LNCaP cells whereas Du145
      expressed wild-type PTEN. All three cell lines were positive for surface
      expression of CXCR4. Reconsitution of PTEN induced a mesenchymal to epithelial
      like morphologic change and inhibited CXCR4-mediated migration and proliferation
      in PC3 cells. Downregulation of PTEN by siRNA enhanced the CXCR4-mediated
      migratory behavior of Du145 cells. By Western blot analysis, we observed that
      PTEN inhibited basal AKT phosphorylation but not ERK1/2 phosphorylation in PTEN
      expressing cells. Upon CXCR4 stimulation, PTEN inhibited ERK1/2 phosphorylation
      but not phosphorylation of AKT. The CXCR4-mediated migration of PC3 cells was
      through the ERK1/2 pathway, as confirmed by chemical inhibitors. On the basis of
      these studies, we suggest that loss of PTEN permits CXCR4-mediated functions in
      prostate cancer cells through the ERK1/2 pathway. Antagonizing CXCR4 and
      downstream signaling cascades may provide an efficient approach for treating
      patients with advanced prostate cancer when hormone therapy fails to the stop the
      growth and containment of tumors.

PMID- 21076048
TI  - B1, a novel amonafide analogue, overcomes the resistance conferred by Bcl-2 in
      human promyelocytic leukemia HL60 cells.
AB  - In the course of screening for novel anticancer compounds, B1 [N-(2
      (dimethylamino)ethyl)-2-aminothiazonaphthalimide], a novel amonafide analogue,
      was generated as a new anticancer candidate. In the present study, B1 displayed
      stronger antitumor effects than amonafide in HL60 cells. We further examined
      whether B1 overcomes the resistance conferred by Bcl-2, as overcoming the
      resistance conferred by Bcl-2 represents an attractive therapeutic strategy
      against cancer. Our viability assay showed that B1 overcomes the resistance
      conferred by Bcl-2 in human promyelocytic leukemia HL60 cells. Various apoptosis
      assessment assays showed that B1 overcomes the resistance conferred by Bcl-2 in
      HL60 cells by inducing apoptosis. Noticeably, we elucidated the marked
      downregulation of 14-3-3sigma protein by B1, indicating that B1 overcomes the
      resistance conferred by Bcl-2 in HL60 cells via 14-3-3sigma. The analysis of
      chromatin immunoprecipitation assay indicated that MBD2 was associated with the
      methylated 14-3-3sigma promoter-associated CpG island and thus interfered with
      transcriptional activity of the methylated promoter. Furthermore, knockdown of
      MBD2, using siRNA transfection, inhibited B1-induced apoptosis and overcame the
      resistance conferred by Bcl-2. Accordingly, these data showed the involvement of
      MBD2 in B1-induced apoptosis and overcoming the resistance conferred by Bcl-2,
      which suggested that MBD2 might guide the development of future anticancer
      agents.

PMID- 21076049
TI  - Re: The role of SATB1 in breast cancer pathogenesis.

PMID- 21076050
TI  - Geographic representation of the jackson heart study cohort to the African
      American population in Jackson, Mississippi.
AB  - Recent advances in geographic information systems software and multilevel
      methodology provide opportunities for more extensive characterization of "at
      risk" populations in epidemiologic studies. The authors used age-restricted,
      geocoded data from the all-African-American Jackson Heart Study (JHS), 2000-2004,
      to demonstrate a novel use of the Lorenz curve and Gini coefficient to determine
      the representativeness of the JHS cohort to the African-American population in a
      geographic setting. The authors also used a spatial binomial model to assess the
      geographic variability in participant recruitment across the Jackson,
      Mississippi, Metropolitan Statistical Area. The overall Gini coefficient, an
      equality measure that ranges from 0 (perfect equality) to 1 (perfect inequality),
      was 0.37 (95% confidence interval (CI): 0.30, 0.45), indicating moderate
      representation. The population of sampled women (Gini coefficient = 0.34, 95% CI:
      0.30, 0.39) tended to be more representative of the underlying population than
      did the population of sampled men (Gini coefficient = 0.49, 95% CI: 0.35, 0.61).
      Representative recruitment of JHS participants was observed in predominantly
      African-American and mixed-race census tracts and in the center of the study
      area, the area nearest the examination clinic. This is of critical importance as
      the authors continue to explore novel approaches to investigate the geographic
      variation in disease etiology.

PMID- 21076051
TI  - Vitamin D receptor genotypes, ultraviolet radiation exposure, and risk of non
      Hodgkin lymphoma.
AB  - Ultraviolet radiation (UVR) exposure may influence risk of non-Hodgkin lymphoma
      (NHL) through vitamin D, with antineoplastic effects mediated through the vitamin
      D receptor (VDR). To explore the role of vitamin D in NHL risk and the potential
      interaction with UVR, the authors genotyped 10 VDR polymorphisms in 2,448 NHL
      patients and 1,981 controls from Denmark and Sweden who were recruited in 1999
      2002. Odds ratios and 95% confidence intervals were computed with logistic
      regression. P values were 2-sided. Most VDR variants (e.g., rs731236/TaqI,
      rs15444410/BsmI) were not associated with overall risk of NHL, but there was some
      evidence of a positive association between rs4760655 and follicular lymphoma risk
      (nominal P(trend) = 0.004, corrected P(trend) = 0.24). There was no support for
      an effect of interaction between VDR variants and UVR exposure on risk of overall
      NHL or B-cell lymphoma subtypes. However, there was some evidence that rs731236
      altered associations between UVR and T-cell NHL risk; while increasing UVR
      frequency lowered T-cell NHL risk among rs731236 TT carriers, an elevated risk
      was observed among rs731236 CC carriers (nominal P(interaction) <= 0.008,
      corrected P(interaction) >= 0.12). VDR does not appear to harbor major
      determinants of NHL risk, except perhaps for follicular lymphoma. Possible
      heterogeneity in effects of UVR exposure on T-cell lymphoma risk by VDR rs731236
      genotype merits further investigation.

PMID- 21076052
TI  - Prehospital non-invasive ventilation for acute cardiogenic pulmonary oedema: an
      evidence-based review.
AB  - BACKGROUND: Non-invasive ventilation (NIV) is increasingly being implemented by
      many ambulance jurisdictions as a standard of care in the out-of-hospital
      management of acute cardiogenic pulmonary oedema (ACPO). This implementation
      appears to be based on the body of evidence from the emergency department (ED)
      setting, with the assumption that earlier administration by paramedics would give
      benefits with regard to inhospital mortality and the rate of endotracheal
      intubation beyond those seen when initiated in the ED. This paper sought to
      identify and review the current level of evidence supporting NIV in the
      prehospital setting. METHODS: Electronic searches of Medline, EMBASE, CINAHL,
      Cochrane Database of Systematic Reviews and Cochrane Database of Controlled
      Trials were conducted and reference lists of relevant articles were hand
      searched. RESULTS: The search identified 12 primary studies documenting the use
      of NIV, either continuous positive airway pressure or bi-level non-invasive
      ventilation, for ACPO in the out-of-hospital setting. Only three studies were
      randomised controlled trials, with none addressing inhospital mortality as a
      primary outcome measure. The majority of articles were non-comparative
      descriptive studies. CONCLUSION: Early prehospital NIV appears to be a safe and
      feasible therapy that results in faster improvement in physiological status and
      may decrease the need for intubation when compared with delayed administration in
      the ED. There is weak evidence that is may decrease mortality. The cost versus
      benefit equation of system-wide prehospital implementation of NIV is unclear and,
      based on the current evidence, should be considered with caution.

PMID- 21076053
TI  - Deliberate self-harm patients in the emergency department: factors associated
      with repeated self-harm among 1524 patients.
AB  - OBJECTIVES: (1) investigate risk factors associated with repeated deliberate self
      harm (DSH) among patients attending the emergency department due to DSH, (2)
      stratify these patients into risk categories for repeated DSH and (3) estimate
      the proportion of repeated DSH within 12 months. DESIGN: A consecutive series of
      individuals who attended one of Scandinavia's largest emergency departments
      during 2003-2005 due to DSH. Data on sociodemographic factors, diagnoses and
      treatment, previous DSH at any healthcare facility in Sweden (2002-2005) and
      circumstances of the index DSH episode were collected from hospital charts and
      national databases. A nationwide register based on follow-ups of any new DSH or
      death by suicide during 2003-2006. MAIN OUTCOME MEASURE: Repeated DSH episode or
      suicide. RESULTS: 1524 patients were included. The cumulative incidence for
      patients repeating DSH within 12 months after the index episode was 26.8% (95%
      CI: 24.6 to 29.0). Risk factors associated with repeating DSH included previous
      DSH, female gender, self-injury as a method for DSH and if the self-injury
      required a surgical procedure, current psychiatric or antidepressant treatment
      and if the patient suffered from a substance use disorder or adult personality
      disorder or did not have children under the age of six. CONCLUSION: Patients
      attending an emergency department due to DSH have a high risk of repeating their
      self-harm behaviour. We present a model for risk stratification for repeated DSH
      describing low-risk (18%), median-risk (28% to 32%) and high-risk (47% to 72%).
      Our results might help caretakers to direct optimal resources to these groups.

PMID- 21076054
TI  - Obituary for the four-hour target.

PMID- 21076055
TI  - Validation of the Taiwan triage and acuity scale: a new computerised five-level
      triage system.
AB  - OBJECTIVE: An ideal emergency department (ED) triage system accurately
      prioritises patients on the basis of the urgency of interventions required to
      avoid under- or over-triage. The objective of this study was to develop and
      validate a five-level Taiwan triage and acuity scale (TTAS) with an electronic
      decision support tool. METHODS: This prospective, multicentre, observational
      study included 10533 patients triaged at 11 academic medical centres, 18 regional
      and four district hospitals. Adult patients presenting to the ED were
      independently triaged by the duty triage nurse in the usual way and trained
      research nurses using TTAS with a computerised decision support system. Weighted
      kappa statistics were used to assess the reproducibility. Hospitalisation, length
      of stay, and medical resource consumption were analysed by TTAS acuity levels.
      RESULTS: Most cases were stratified into levels 2 to 3 by the existing four-level
      triage system, whereas the TTAS stratified most patients to levels 3 (41.4%) and
      4 (25.0%), and only a small number to level 1 (3.9%) (resuscitation; most
      urgent). Weighted kappa for TTAS assignment was 0.87 (95% CI 0.85 to 0.89). The
      decrease in mean medical resource consumption and hospitalisation rate was
      statistically significant with each decrease in the TTAS triage acuity level. The
      length of stay also decreased significantly as the TTAS level acuity fell from
      levels 2 to 5. CONCLUSIONS: The TTAS was found to be a reliable triage system
      that accurately prioritises the treatment needed to avoid overtriage, more
      efficiently deploying the appropriate resources to ED patients.

PMID- 21076057
TI  - Mutation and epigenetic molecular clocks in cancer.
AB  - A quandary of evolution is how to measure change over time. A natural inclination
      is to use morphologic criteria-the greater the differences between two
      phenotypes, the greater amount of time needed to evolve these differences.
      However, appearances may be deceiving, and another approach to infer time is with
      molecular clocks. Here, the greater the differences between two genomes, on
      average the greater the time since a common ancestor. Recent advances in DNA
      sequencing shed new light on how human cancers might evolve.

PMID- 21076058
TI  - A naturally occurring, soluble antagonist of human IL-23 inhibits the development
      and in vitro function of human Th17 cells.
AB  - Th17 CD4 cells are critical to inflammation. Their secretion of IL-17 drives
      inflammation in human diseases, including inflammatory bowel disease.
      Differentiation of mature Th17 cells depends on stimulation with IL-6, TGF-beta,
      and IL-21 and the induction of RORgammat, but IL-23 is essential to Th17
      phenotype, stability, and function. Induction of Th17 cells can be antagonized by
      IL-4 or IFN-gamma, but mechanisms through which terminal differentiation can be
      inhibited have not been identified. Human IL-23Ralpha (HuIL23Ralpha)-chain mRNA
      transcripts exist that lack exon 9 ("Delta9"); these are translated to a
      truncated receptor containing the entire external domain. This soluble variant of
      the HuIL23Ralpha-chain antagonizes Th17 maturation. It is secreted and present at
      low levels in the blood. It represents 10% of HuIL23Ralpha-chain mRNA, binds IL
      23 in solution, and inhibits the phosphorylation of STAT3 caused by IL-23. In in
      vitro Th17 cell differentiation experiments, Delta9 inhibits the production of
      the Th17-associated cytokines IL-17A and IL-17F. Delta9 does not bind IL-12;
      thus, it is a specific inhibitor of IL-23 and a modulator of Th17 cells. Our
      results indicate that this soluble form of HuIL23Ralpha likely functions to
      regulate Th17 activity.

PMID- 21076059
TI  - Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but
      does not diminish humoral immunity and efficacy of a DNA/MVA vaccine.
AB  - The influence of preexisting immunity to viral vectors is a major issue for the
      development of viral-vectored vaccines. In this study, we investigate the effect
      of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a
      DNA/modified vaccinia Ankara (MVA) SIV vaccine in rhesus macaques using a
      pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV
      specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral
      immunity. In addition, preexisting immunity did not diminish the control of an
      SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was
      150- and 17-fold lower, respectively, in preimmune animals compared with those of
      control animals. The peak and set point viremia correlated directly with
      colorectal virus at 2 wk postchallenge suggesting that early control of virus
      replication at the site of viral challenge was critical for viral control.
      Factors that correlated with early colorectal viral control included 1) the
      presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the
      native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T
      cells displaying the CCR5 viral coreceptor. The frequency of SIV-specific CD8 T
      cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with
      early colorectal viral control. These results suggest that preexisting vaccinia
      virus immunity may not limit the potential of recombinant MVA vaccines to elicit
      humoral immunity and highlight the importance of immunodeficiency virus vaccines
      achieving early control at the mucosal sites of challenge.

PMID- 21076060
TI  - The Igkappa gene enhancers, E3' and Ed, are essential for triggering
      transcription.
AB  - The mouse Igkappa gene locus has three known transcriptional enhancers: an
      intronic enhancer (Ei), a 3' enhancer (E3'), and a further downstream enhancer
      (Ed). Previous studies on B lymphocytes derived from mutant embryonic stem cells
      have shown that deletion of either Ei or E3' significantly reduces Igkappa gene
      rearrangement, whereas the combined deletion of both Ei and E3' eliminates such
      recombination. Furthermore, deletion of either E3' or Ed significantly reduces
      rearranged Igkappa gene transcription. To determine whether the combined presence
      of both E3' and Ed are essential for Igkappa gene expression, we generated
      homozygous double knockout (DKO) mice with targeted deletions in both elements.
      Significantly, homozygous DKO mice were unable to generate kappa(+) B cells both
      in bone marrow and the periphery and exhibited surface expression almost
      exclusively of Iglambda-chains, despite the fact that they possessed potentially
      functional rearranged Igkappa genes. Compared with their single-enhancer-deleted
      counterparts, Igkappa loci in homozygous DKO mice exhibited dramatically reduced
      germline and rearranged gene transcription, lower levels of gene rearrangement
      and histone H3 acetylation, and markedly increased DNA methylation. This
      contributed to a partial developmental block at the pre-B cell stage of
      development. We conclude that the two downstream enhancers are essential in
      Igkappa gene expression and that Ei in homozygous DKO mice is incapable of
      triggering Igkappa gene transcription. Furthermore, these results reveal
      unexpected compensatory roles for Ed in E3' knockout mice in triggering germline
      transcription and Vkappa gene rearrangements to both Jkappa and RS elements.

PMID- 21076061
TI  - Immunological effects of sublingual immunotherapy: clinical efficacy is
      associated with modulation of programmed cell death ligand 1, IL-10, and IgG4.
AB  - Sublingual immunotherapy (SLIT) is an alternate route of administration of
      allergen-specific immunotherapy with an improved safety profile; to clarify the
      immune mechanisms elicited by this therapy, we analyzed the clinical and
      immunologic effects of SLIT in patients with a clinical history of ragweed
      sensitization. To analyze possible difference among immunotherapeutic protocols,
      we also compared patients receiving preseasonal, seasonal, or prolonged
      sublingual therapy (>= 3 y); patients receiving symptomatic therapy alone were
      enrolled as well in the study. Clinical and immunological parameters were
      measured twice in and out of the pollination period. Clinical benefits, as
      measured by the visual analog scale for symptoms and for use of drugs, were
      evident in all three groups of individuals receiving immunotherapy, but were
      significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT
      resulted in increased IL-10 production, programmed cell death ligand 1
      expression, and concentration of allergen-specific IgG4, as well as in the
      reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is
      associated with modulation of programmed cell death ligand 1 expression and IL-10
      synthesis and favors the production of allergen-specific IgG4. These effects are
      evident from the first pollen season, independently from therapeutic regimen
      (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain
      full clinical efficacy. A more detailed understanding of the interaction of
      allergen and APCs within the oral mucosa will allow improved targeting of allergy
      vaccine.

PMID- 21076062
TI  - NKG2D is required for NK cell activation and function in response to E1-deleted
      adenovirus.
AB  - Despite high transduction efficiency in vivo, the application of recombinant E1
      deleted adenoviral vectors for in vivo gene therapy has been limited by the
      attendant innate and adaptive immune responses to adenoviral vectors. NK cells
      have been shown to play an important role in innate immune elimination of
      adenoviral vectors in vivo. However, the mechanisms underlying NK cell activation
      and function in response to adenoviral vectors remain largely undefined. In this
      study, we showed that NK cell activation upon adenoviral infection was dependent
      on accessory cells such as dendritic cells and macrophages and that cell contact
      dependent signals from the accessory cells are necessary for NK cell activation.
      We further demonstrated that ligands of the NK activating receptor NKG2D were
      upregulated in accessory cells upon adenoviral infection and that blockade of
      NKG2D inhibited NK cell activation upon adenoviral infection, leading to a delay
      in adenoviral clearance in vivo. In addition, NKG2D was required for NK cell
      mediated cytolysis on adenovirus-infected targets. Taken together, these results
      suggest that efficient NK cell activation and function in response to adenoviral
      infection is critically dependent on the NKG2D pathway, which understanding may
      assist in the design of effective strategies to improve the outcome of adenovirus
      mediated gene therapy.

PMID- 21076063
TI  - Cutting edge: The transcription factor Kruppel-like factor 4 regulates the
      differentiation of Th17 cells independently of RORgammat.
AB  - Th17 cells play a significant role in inflammatory and autoimmune responses.
      Although a number of molecular pathways that contribute to the lineage
      differentiation of T cells have been discovered, the mechanisms by which lineage
      commitment occurs are not fully understood. Transcription factors play a key role
      in driving T cells toward specific lineages. We have identified a role for the
      transcription factor Kruppel-like factor (KLF) 4 in the development of IL-17
      producing CD4(+) T cells. KLF4 was required for the production of IL-17, and
      further, chromatin immunoprecipitation analysis demonstrated binding of KLF4 to
      the IL-17 promoter, indicating a direct effect on the regulation of IL-17.
      Further, KLF4-deficient T cells upregulated expression of retinoic acid-related
      orphan receptor gammat similar to wild-type during the polarization process
      toward Th17, suggesting that these two transcription factors are regulated
      independently.

PMID- 21076064
TI  - A conserved enhancer element differentially regulates developmental expression of
      CD5 in B and T cells.
AB  - We previously identified an enhancer element upstream of the mouse cd5 gene that
      was required in reporter assays for the induction of cd5 promoter activity by BCR
      cross-linking. This element is highly conserved in placental mammals. To
      determine its physiological role, we have now generated mice with a targeted
      deletion of the enhancer. The result is the loss of CD5 expression in peritoneal
      and splenic B-1a cells of adult mice and an inability to induce CD5 by cross
      linking of the BCR on splenic B-2 cells. Surprisingly, CD5 expression on B-1a
      cells of neonatal mice was only minimally compromised. Cd5 enhancer deletion also
      had only a modest effect on CD5 expression in the T lineage. Thus, this enhancer
      provides age- and tissue-specific regulation of CD5 expression and is an example
      of the utilization of different modes of regulation of expression in T and B
      cells.

PMID- 21076066
TI  - CD8 T cell-intrinsic GITR is required for T cell clonal expansion and mouse
      survival following severe influenza infection.
AB  - The regulation of T cell expansion by TNFR family members plays an important role
      in determining the magnitude of the immune response to pathogens. As several
      members of the TNFR family, including glucocorticoid-induced TNFR-related protein
      (GITR), are found on both regulatory and effector T cells, there is much interest
      in understanding how their effects on these opposing arms of the immune system
      affect disease outcome. Whereas much work has focused on the role of GITR on
      regulatory T cells, little is known about its intrinsic role on effector T cells
      in an infectious disease context. In this study, we demonstrate that GITR
      signaling on CD8 T cells leads to TNFR-associated factor (TRAF) 2/5-dependent,
      TRAF1-independent NF-kappaB induction, resulting in increased Bcl-x(L). In vivo,
      GITR on CD8 T cells has a profound effect on CD8 T cell expansion, via effects on
      T cell survival. Moreover, GITR is required on CD8 T cells for enhancement of
      influenza-specific CD8 T cell expansion upon administration of agonistic anti
      GITR Ab, DTA-1. Remarkably, CD8 T cell-intrinsic GITR is essential for mouse
      survival during severe, but dispensable during mild respiratory influenza
      infection. These studies highlight the importance of GITR as a CD8 T cell
      costimulator during acute viral infection, and argue that despite the similarity
      among several TNFR family members in inducing T lymphocyte survival, they clearly
      have nonredundant functions in protection from severe infection.

PMID- 21076065
TI  - Actin-bundling protein L-plastin regulates T cell activation.
AB  - Engagement of TCRs induces actin rearrangements, which are critical for T cell
      activation. T cell responses require new actin polymerization, but the
      significance of higher-order actin structures, such as microfilament bundles, is
      unknown. To determine the role of the actin-bundling protein leukocyte-plastin (L
      plastin; LPL) in this process, T cells from LPL(-/-) mice were studied. LPL(-/-)
      T cells were markedly defective in TCR-mediated cytokine production and
      proliferation. LPL(-/-) T cells also spread inefficiently on surfaces with
      immobilized TCR ligands and formed smaller immunological synapses with APCs,
      likely due to defective formation of lamellipodia. LPL(-/-) mice showed delayed
      rejection of skin allografts after release from immunosuppression. Moreover, LPL(
      /-) mice developed much less severe neurologic symptoms in experimental
      autoimmune encephalomyelitis, which correlated with impaired T cell responses to
      Ag, manifested by reduced proliferation and production of IFN-gamma and IL-17.
      Thus, LPL-dependent actin bundling facilitates the formation of lamellipodia and
      normal immunological synapses and thereby enables T cell activation.

PMID- 21076067
TI  - A dendritic cell population generated by a fusion of GM-CSF and IL-21 induces
      tumor-antigen-specific immunity.
AB  - We have previously shown that the fusion of GM-CSF and IL-21 (GIFT-21) possesses
      a potent immune stimulatory effect on myeloid cells. In this study, we define the
      effect of GIFT-21 on naive murine monocytes (GIFT-21 dendritic cells [DCs]),
      which express increased levels of Gr-1, CD45R, MHC class I, CD80, CD86, and CXCR4
      and suppress CD11c and MHC class II. Compared with conventional dendritic cells,
      GIFT-21 DCs produced substantially more CCL2, IL-6, TNF-alpha, and IFN-alpha and
      induced significantly greater production of IFN-gamma by CD8(+) T cells in MHC
      class I-restricted Ag presentation assays. B16 melanoma and D2F2 Neu breast
      cancer growth was inhibited in mice treated with Ag-naive GIFT-21 DCs. This
      effect was lost in CD8(-/-) and CCR2(-/-) mice and when mice were treated with
      beta(2)-microglobulin-deficient GIFT-21 DCs, indicating that GIFT-21 DCs migrated
      to and sampled from the tumors to present tumor Ags to CCL2 recruited CD8(+) T
      cells via MHC class I. We propose that autologous GIFT-21 DCs may serve as a cell
      therapy platform for the treatment of cancer.

PMID- 21076069
TI  - A nonredundant role for canonical NF-kappaB in human myeloid dendritic cell
      development and function.
AB  - The plastic role of dendritic cells (DCs) in the regulation of immune responses
      has made them interesting targets for immunotherapy, but also for pathogens or
      tumors to evade immunity. Functional alterations of DCs are often ascribed to
      manipulation of canonical NF-kappaB activity. However, though this pathway has
      been linked to murine myeloid DC biology, a detailed analysis of its importance
      in human myeloid DC differentiation, survival, maturation, and function is
      lacking. The myeloid DC subsets include interstitial DCs and Langerhans cells. In
      this study, we investigated the role of canonical NF-kappaB in human myeloid DCs
      generated from monocytes (monocyte-derived DCs [mo-DCs]) or CD34(+) progenitors
      (CD34-derived myeloid DCs [CD34-mDCs]). Inhibition of NF-kappaB activation during
      and after mo-DC, CD34-interstitial DC, or CD34-Langerhans cell differentiation
      resulted in apoptosis induction associated with caspase 3 activation and loss of
      mitochondrial transmembrane potential. Besides regulating survival, canonical NF
      kappaB activity was required for the acquisition of a DC phenotype. Despite
      phenotypic differences, however, Ag uptake, costimulatory molecule and CCR7
      expression, as well as T cell stimulatory capacity of cells generated under NF
      kappaB inhibition were comparable to control DCs, indicating that canonical NF
      kappaB activity during differentiation is redundant for the development of
      functional APCs. However, both mo-DC and CD34-mDC functionality were reduced by
      NF-kappaB inhibition during activation. In conclusion, canonical NF-kappaB
      activity is essential for the development and function of mo-DCs as well as CD34
      mDCs. Insight into the role of this pathway may help in understanding how
      pathogens and tumors escape immunity and aid in developing novel treatment
      strategies aiming to interfere with human immune responses.

PMID- 21076068
TI  - Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the
      transcription factor eomesodermin.
AB  - A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation
      of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of
      CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of
      the T-box family of transcription factors and plays critical roles in effector
      cell function and memory cell fitness of CD8(+) T lymphocytes. We provide
      evidence in this study that DN T cells exhibit dysregulated expression of Eomes
      in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes
      prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice.
      Although Eomes has critical physiological roles in the function and homeostasis
      of CD8(+) T cells, overexpression of Eomes appears to enable pathological
      induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of
      Eomes emerges as a therapeutic target for DN T cell ablation in ALPS.

PMID- 21076070
TI  - The inflammatory response after an epidermal burn depends on the activities of
      mouse mast cell proteases 4 and 5.
AB  - A second-degree epidermal scald burn in mice elicits an inflammatory response
      mediated by natural IgM directed to nonmuscle myosin with complement activation
      that results in ulceration and scarring. We find that such burn injury is
      associated with early mast cell (MC) degranulation and is absent in WBB6F1
      Kit(W)/Kit(Wv) mice, which lack MCs in a context of other defects due to a
      mutation of the Kit receptor. To address further an MC role, we used transgenic
      strains with normal lineage development and a deficiency in a specific secretory
      granule component. Mouse strains lacking the MC-restricted chymase, mouse MC
      protease (mMCP)-4, or elastase, mMCP-5, show decreased injury after a second
      degree scald burn, whereas mice lacking the MC-restricted tryptases, mMCP-6 and
      mMCP-7, or MC-specific carboxypeptidase A3 activity are not protected. Histologic
      sections showed some disruption of the epidermis at the scald site in the
      protected strains suggesting the possibility of topical reconstitution of full
      injury. Topical application of recombinant mMCP-5 or human neutrophil elastase to
      the scalded area increases epidermal injury with subsequent ulceration and
      scarring, both clinically and morphologically, in mMCP-5-deficient mice.
      Restoration of injury requires that topical administration of recombinant mMCP-5
      occurs within the first hour postburn. Importantly, topical application of human
      MC chymase restores burn injury to scalded mMCP-4-deficient mice but not to mMCP
      5-deficient mice revealing nonredundant actions for these two MC proteases in a
      model of innate inflammatory injury with remodeling.

PMID- 21076072
TI  - Antibodies and lentiviruses that specifically recognize a T cell epitope derived
      from HIV-1 Nef protein and presented by HLA-C.
AB  - HIV selectively downregulates HLA-A and -B from the surfaces of infected cells to
      avoid detection by the immune system. In contrast, the HLA-C molecules are highly
      resistant to this downregulation. High expression level of HLA-C on the cell
      surface, which correlates with a single nucleotide polymorphism, is also
      associated with lower viral loads and slower progression to AIDS. These findings
      strongly suggest that HIV-1-derived peptides are efficiently presented by HLA-C
      and trigger the elimination of infected cells. Accordingly, the ability to detect
      these HLA-C-peptide complexes may be used for therapeutic targeting of HIV-1
      infected cells and for measuring effective presentation of vaccine candidates
      after immunization with HIV-1-related proteins or genes. However, low level of
      HLA-C expression on the cell surface has impeded the development of such complex
      recognizing reagents. In this study, we describe the development of a high
      affinity human Ab that specifically interacts, at low pM concentrations, with a
      conserved viral T cell epitope derived from HIV-1 Nef protein and presented by
      HLA-C. The human Ab selectively detects this complex on different cells and does
      not interact with a control complex that differed only in the presented peptide.
      Engineering lentiviruses to display this Ab endowed them with the same
      specificity as the Ab, whereas coexpressing the Ab and Fas ligand enables the
      lentiviruses to kill specifically Nef-presenting cells. Abs and pseudoviruses
      with such specificity are likely to be highly valuable as building blocks for
      specific targeting and killing of HIV-1-infected cells.

PMID- 21076073
TI  - A transhumanist fault line around disability: morphological freedom and the
      obligation to enhance.
AB  - The transhumanist literature encompasses diverse non-novel positions on questions
      of disability and obligation reflecting long-running political philosophical
      debates on freedom and value choice, complicated by the difficulty of projecting
      values to enhanced beings. These older questions take on a more concrete form
      given transhumanist uses of biotechnologies. This paper will contrast the views
      of Hughes and Sandberg on the obligations persons with "disabilities" have to
      enhance and suggest a new model. The paper will finish by introducing a
      distinction between the responsibility society has in respect of the presence of
      impairments and the responsibility society has not to abandon disadvantaged
      members, concluding that questions of freedom and responsibility have renewed
      political importance in the context of enhancement technologies.

PMID- 21076074
TI  - Moral transhumanism.
AB  - In its basic sense, the term "human" is a term of biological classification: an
      individual is human just in case it is a member of the species Homo sapiens. Its
      opposite is "nonhuman": nonhuman animals being animals that belong to other
      species than H. sapiens. In another sense of human, its opposite is "inhuman,"
      that is cruel and heartless (cf. "humane" and "inhumane"); being human in this
      sense is having morally good qualities. This paper argues that biomedical
      research and therapy should make humans in the biological sense more human in the
      moral sense, even if they cease to be human in the biological sense. This serves
      valuable biomedical ends like the promotion of health and well-being, for if
      humans do not become more moral, civilization is threatened. It is unimportant
      that humans remain biologically human, since they do not have moral value in
      virtue of belonging to H. sapiens.

PMID- 21076071
TI  - Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A
      domain induces blisters via complement activation in experimental bullous
      pemphigoid model.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG
      autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen
      17 (hCOL17), which triggers blister formation via complement activation. Previous
      in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger
      pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role
      of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a
      recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized
      mice, this mAb effectively reproduced a BP phenotype that included subepidermal
      blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell
      degranulation. Subsequently, alanine substitutions at various C1q binding sites
      were separately introduced to the Fc region of the IgG1 mAb. Among these mutated
      mAbs, the one that was mutated at the P331 residue completely failed to activate
      the complement in vitro and drastically lost pathogenic activity in COL17
      humanized mice. These findings indicate that P331 is a key residue required for
      complement activation and that IgG1-dependent complement activation is essential
      for blister formation in BP. This study is, to our knowledge, the first direct
      evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and
      it raises the possibility that IgG1 mAbs with Fc modification may be used to
      block pathogenic epitopes in autoimmune diseases.

PMID- 21076075
TI  - Enhanced humans versus "normal people": elusive definitions.
AB  - A key aspect of transhumanist thought involves the modification or augmentation
      of human physical and mental capabilities--a form of intervention often
      encapsulated under the term "enhancement." This article provides an overview of
      the concept of enhancement, focusing on six major areas in which usages of the
      term become slippery and controversial: normal or species-typical functioning,
      therapeutics or healing, natural functioning, human nature, authenticity, and the
      ambiguity between "more" and "better." I argue that we need to be aware of the
      tendency to embed the concept of enhancement within stark binary oppositions that
      seem perfectly reasonable at first glance, but that in fact yield little more
      than conceptual muddles if they are not handled carefully.

PMID- 21076079
TI  - Generation of functional oocytes and spermatids from fetal primordial germ cells
      after ectopic transplantation in adult mice.
AB  - Primordial germ cells (PGCs) are undifferentiated germ cells in developing
      fetuses. As these cells give rise to definitive oocytes and spermatozoa that
      contribute to new life in the next generation, their development must be under
      strict control, regarding genetic and epigenetic aspects. However, we do not know
      to what extent their development depends on the specific milieu. In this study,
      we transplanted mouse PGCs collected from male and female gonads at 12.5 days
      postcoitum, together with gonadal somatic cells, under kidney capsules of adult
      mice. The transplanted PGC and gonadal somatic cells constructed testis-like and
      ovary-like tissues, respectively, under the kidney capsules within 4 wk. Normal
      appearing round spermatids and fully grown germinal vesicle (GV) oocytes
      developed within these tissues. Ectopic spermatogenesis continued thereafter,
      while oogenesis consisted of only a single wave. The injection of these round
      spermatids directly into mature in vivo-derived oocytes led to the birth at term
      of normal pups. PGC-derived GV oocytes were isolated, induced to mature in vitro,
      and injected with normal spermatozoa. The injected oocytes were successfully
      fertilized and developed into normal pups. Our findings demonstrate the
      remarkable flexibility of PGC development, which can proceed up to the functional
      gamete stage under spatially and temporally noninnate conditions. This
      transplantation system may provide a unique technical basis for induction of the
      development of early germ cells of exogenous origins, such as those from
      embryonic stem cells.

PMID- 21076077
TI  - PPARG regulates gonadotropin-releasing hormone signaling in LbetaT2 cells in
      vitro and pituitary gonadotroph function in vivo in mice.
AB  - Peroxisome proliferators-activated receptor gamma (PPARG) ligands improve insulin
      sensitivity in type 2 diabetes and polycystic ovarian syndrome (PCOS). Despite
      clinical studies showing normalization of pituitary responsiveness to
      gonadotropin-releasing hormone (GnRH) in patients with PCOS, the precise role of
      PPARG in regulating the hypothalamic-pituitary-gonadal axis remains unclear. In
      the present study, we tested the hypothesis that the PPARG agonist rosiglitazone
      has a direct effect on the pituitary. In mouse LbetaT2 immortalized gonadotrophs,
      rosiglitazone treatment inhibited GnRH stimulation of the stress kinases p38MAPK
      and MAPKs/JNKs, but did not alter activation of ERKs, both in the presence and
      absence of activin. Furthermore, p38MAPK signaling was critical for both Lhb and
      Fshb promoter activity, and rosiglitazone suppressed the GnRH-mediated induction
      of Lhb and Fshb mRNA. Depletion of PPARG using a lentivirally encoded short
      hairpin RNA abolishes the effect of rosiglitazone to suppress activation of JNKs
      and induction of the transcription factors EGR1 and FOS as well as the
      gonadotropin genes Lhb and Fshb. Lastly, we show conditional knockout of Pparg in
      pituitary gonadotrophs caused an increase in luteinizing hormone levels in female
      mice, a decrease in follicle-stimulating hormone in male mice, and a fertility
      defect characterized by reduced litter size. Taken together, our data support a
      direct role for PPARG in modulating pituitary function in vitro and in vivo.

PMID- 21076080
TI  - Zinc requirement during meiosis I-meiosis II transition in mouse oocytes is
      independent of the MOS-MAPK pathway.
AB  - Zinc is essential for many biological processes, including proper functioning of
      gametes. We recently reported that zinc levels rise by over 50% during oocyte
      maturation and that attenuation of zinc availability during this period could be
      achieved using the membrane-permeable heavy metal chelator N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN). This zinc insufficiency resulted in
      formation of large polar bodies, failure to establish metaphase II arrest, and
      impaired establishment of cortical polarity. As these phenotypes resemble those
      of MOS null oocytes, we examined the impact of zinc insufficiency on the MOS-MAPK
      pathway. Reduced levels of both MOS protein and phosphorylation of MAP2K1/2 are
      observed in zinc-insufficient oocytes; however, these differences appear only
      after completion of the first meiotic division. In addition, activation of the
      downstream effector of the MOS pathway, MAPK3/1, is not affected by zinc
      insufficiency, and reduced MOS levels are observed only with the presence of TPEN
      after the first polar body extrusion. These data are inconsistent with the
      hypothesis that reduced MOS mediates the observed phenotype. Finally, MOS
      overexpression does not rescue the phenotype of zinc-insufficient oocytes,
      confirming that the observed disruption of asymmetric division and spindle
      abnormalities cannot be attributed to impaired MOS signaling. Zinc-insufficient
      oocytes do not increase maturation promoting factor (MPF) activity following the
      first meiotic division, and increasing MPF activity through expression of
      nondegradable cyclin B1 partially rescues the ability of zinc-insufficient
      oocytes to enter metaphase II. Although we have shown that zinc has a novel role
      in the meiotic cell cycle, it is not mediated through the MOS-MAPK pathway.

PMID- 21076081
TI  - Inhibition of PIK3 signaling pathway members by the ovotoxicant 4
      vinylcyclohexene diepoxide in rats.
AB  - 4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that specifically
      destroys primordial and small primary follicles in the ovaries of rats and mice,
      is thought to target an oocyte-expressed tyrosine kinase receptor, Kit. This
      study compared the temporal effect of VCD on protein distribution of KIT and its
      downstream PIK3-activated proteins, AKT and FOXO3. Postnatal Day 4 Fischer 344
      rat ovaries were cultured in control media +/- VCD (30 MUM) for 2-8 days (d2-d8).
      KIT, AKT, phosphorylated AKT, FOXO3, and pFOXO3 protein levels were assessed by
      Western blotting and/or immunofluorescence staining with confocal microscopy.
      Phosphorylated AKT was decreased (P < 0.05) in oocyte nuclei in primordial (39%
      decrease) and small primary (37% decrease) follicles within 2 days of VCD
      exposure. After d4, VCD reduced (P < 0.05) oocyte staining for KIT (primordial,
      44% decrease; small primary, 39% decrease) and FOXO3 (primordial, 40% decrease;
      small primary, 36% decrease) protein. Total AKT and pFOXO3 were not affected by
      VCD at any time. Akt1 mRNA, as measured by quantitative RT-PCR, was reduced (P <
      0.05) by 23% on d4 of VCD exposure, but returned to control levels on d6 and d8.
      VCD exposure reduced Foxo3a mRNA by 26% on d6 (P < 0.05) and by 23% on d8 (P <
      0.1). These results demonstrate that the earliest observed effect of VCD is an
      inhibition of phosphorylation and nuclear localization of AKT in the oocyte of
      primordial and small primary follicles. This event is followed by reductions in
      KIT and FOXO3 protein subcellular distribution prior to changes in mRNA. Thus,
      these findings further support that VCD induces ovotoxicity by directly targeting
      the oocyte through posttranslational inhibition of KIT-mediated signaling
      components.

PMID- 21076082
TI  - Transcript profiling of individual twin blastomeres derived by splitting two-cell
      stage murine embryos.
AB  - In invertebrates and amphibians, informational macromolecules in egg cytoplasm
      are organized to provide direction to the formation of embryonic lineages, but it
      is unclear whether vestiges of such prepatterning exist in mammals. Here we
      examined whether twin blastomeres from 2-cell stage mouse embryos differ in mRNA
      content. mRNA from 26 blastomeres derived from 13 embryos approximately mid-way
      through their second cell cycle was subjected to amplification. Twenty amplified
      samples were hybridized to arrays. Of those samples that hybridized successfully,
      12 samples in six pairs were used in the final analysis. Probes displaying
      normalized values >0.25 (n = 4573) were examined for consistent bias in
      expression within blastomere pairs. Although transcript content varied between
      both individual embryos and twin blastomeres, no consistent asymmetries were
      observed for the majority of genes, with only 178 genes displaying a >1.4-fold
      difference in expression across all six pairs. Although class discovery
      clustering showed that blastomere pairs separated into two distinct groups in
      terms of their differentially expressed genes, when the data were tested for
      significance of asymmetrical expression, only 39 genes with >1.4-fold change
      ratios in six of six blastomere pairs passed the two-sample t-test (P < 0.05).
      Transcripts encoding proteins implicated in RNA processing and cytoskeletal
      organization were among the most abundant, differentially distributed mRNA,
      suggesting that a stochastically based lack of synchrony in cell cycle
      progression between the two cells might explain at least some and possibly all of
      the asymmetries in transcript composition.

PMID- 21076083
TI  - Impaired mitochondrial function in the preimplantation embryo perturbs fetal and
      placental development in the mouse.
AB  - The preimplantation embryo is sensitive to its environment and, despite having
      some plasticity to adapt, environmental perturbations can impair embryo
      development, metabolic homeostasis, fetal and placental development, and
      offspring health. This study used an in vitro model of embryo culture with
      increasing mitochondrial inhibition to directly establish the effect of impaired
      mitochondrial function on embryonic, fetal, and placental development. Culture in
      the absence of the carbohydrate pyruvate significantly increased blastocyst
      glucose oxidation via glycolysis to maintain normal levels of ATP and
      tricarboxylic acid (TCA) cycle activity. This culture resulted in a significant
      reduction in blastocyst development, trophectoderm cell number, and respiration
      rate but, importantly, did not impair implantation rates or fetal and placental
      development. In contrast, increasing concentrations of the mitochondrial
      inhibitor amino-oxyacetate (AOA) impaired glycolysis, TCA cycle activity,
      respiration rate, and ATP production; incrementally reduced blastocyst
      development; and decreased blastocyst inner cell mass and trophectoderm cell
      numbers. Importantly, AOA did not affect implantation rates; however, 5 MUM AOA
      significantly reduced placental growth but not fetal growth, increasing the
      fetal:placental weight ratio. Furthermore, 50 MUM AOA significantly reduced both
      placental and fetal growth but not the fetal:placental weight ratio. Hence, this
      study demonstrates that a threshold of mitochondrial function is required for
      normal development, and despite developmental plasticity of the embryo, impaired
      mitochondrial function in the embryo affects subsequent fetal and placental
      growth. These results highlight the importance of mitochondrial function in
      regulating pre- and postimplantation development; however, the effect on
      offspring health remains unknown.

PMID- 21076084
TI  - Regulation of anti-Mullerian hormone production in the cow: a multiscale study at
      endocrine, ovarian, follicular, and granulosa cell levels.
AB  - Anti-Mullerian hormone (AMH) is an endocrine marker that can help predict
      superovulatory responses to treatments administered to cows for embryo
      production. However, the optimal time of the estrous cycle at which a blood test
      should be performed for a highly reliable prognosis has not yet been established.
      Moreover, little is known about the regulation of AMH production. To answer these
      questions, a study was designed to investigate the regulation of AMH production
      in cows selected for their high or low ovulatory responses to superovulation. At
      the granulosa cell level, AMH production was inhibited by follicle-stimulating
      hormone but enhanced by bone morphogenetic proteins. At the follicular level, the
      expression of AMH within the follicle was dependent on the stage of follicular
      development. At the ovarian level, the size of the pool of small antral growing
      follicles determined ovarian AMH production. At the endocrine level, AMH followed
      a specific dynamic profile during the estrous cycle, which occurred independently
      of the follicular waves of terminal follicular development. Cows selected for
      their high or low responses to superovulation did not differ in the regulation of
      AMH production, but cows with higher responses had higher plasma AMH
      concentrations throughout the cycle. The optimal period of the estrous cycle at
      which to measure AMH concentrations with the aim of selecting the best cows for
      embryo production was found to be at estrus and after Day 12 of the cycle. Based
      on this multiscale study, we propose a model that integrates the different
      regulatory levels of AMH production.

PMID- 21076086
TI  - Religion, suffering, and self-rated health among older Mexican Americans.
AB  - OBJECTIVES: The purpose of this study is to examine the relationship between
      religiously based beliefs about suffering and health among older Mexicans.
      METHODS: A nationwide survey of older Mexican Americans was conducted (N=1,005).
      Questions were administered to assess beliefs about finding positive outcomes in
      suffering, the benefits of suffering in silence, other dimensions of religion,
      and health. RESULTS: The findings suggest that older Mexican Americans who use
      their faith to find something positive in the face of suffering tend to rate
      their health more favorably. In contrast, older Mexican Americans who believe
      that it is important to suffer in silence tend to rate their health less
      favorably. DISCUSSION: Moving beyond measures of church attendance to explore
      culturally relevant beliefs about suffering provides important insight into the
      relationship between religion and health among older Mexican Americans.

PMID- 21076085
TI  - Hospice use among urban Black and White U.S. nursing home decedents in 2006.
AB  - PURPOSE: Medicare hospice is a valuable source of quality care at the end of
      life, but its lower use by racial minority groups is of concern. This study
      identifies factors associated with hospice use among urban Black and White
      nursing home (NH) decedents in the United States. DESIGN AND METHODS: Multiple
      data sources are combined and multilevel logistic regression is utilized to
      examine hospice use among urban Black and White NH residents who had access to
      hospice and died in 2006 (N = 288,202). RESULTS: In NHs, Blacks are less likely
      to use hospice than Whites (35.4% vs. 39.3%), even when controlling for
      covariates, interactions, and clustering of decedents in NHs and counties
      (adjusted odds ratio = 0.81, 95% confidence interval = 0.77-0.86). Variation in
      hospice use is greater among subgroups of Blacks than between Blacks and Whites,
      and these variations are predominantly due to individual-level factors, with some
      influence of NH-level factors. Hospice use is higher for Blacks versus Whites
      with do-not-resuscitate orders and lower for Blacks versus Whites with congestive
      heart failure (CHF). Additionally, hospice use is greater among Blacks with
      versus without do-not-resuscitate or do-not-hospitalize orders or cancer and
      those in low-tier versus other NHs. There was also lower hospice use among Blacks
      with versus without CHF. IMPLICATIONS: Efforts to reduce racial differences in
      hospice use should attend to individual-level factors. Heightening use of advance
      directives and targeting Blacks with CHF for hospice could be particularly
      helpful.

PMID- 21076087
TI  - Cerebral oxygenation in wake and during sleep and its relationship to cognitive
      function in community-dwelling older adults without sleep disordered breathing.
AB  - BACKGROUND: This descriptive cross-sectional study investigated the relationships
      between cerebral oxygen reserve and cognitive function in community-dwelling
      older adults. METHODS: Participants (72 women and 40 men) underwent standard
      polysomnography, including regional measures of percent oxyhemoglobin saturation
      (rcSO(2)) determined by cerebral oximetry. Two variables were used to calculate
      cerebral oxygen reserve: (a) awake rcSO(2) (mean presleep rcSO(2)) and (b) the
      change in rcSO(2) from before sleep to the end of the first non-rapid-eye
      movement cycle. General linear models, adjusted for the effects of education and
      occupation, tested differences in performance on standard tests of memory,
      attention, and speed of mental processing. RESULTS: Awake rcSO(2) values were
      normal (60%-79.9%) in 64 participants, marginal (50%-59.9%) in 41, and low (43%
      49.9%) in 7. Participants with normal awake levels had higher cognitive function
      than those with low levels (p < .05). Changes in rcSO(2) were greatest in
      participants with marginal awake rcSO(2) values; among whom, those who increased
      rcSO(2) during sleep (n = 17) had better memory function than the 24 who did not
      (p < .05). CONCLUSIONS: Low awake rcSO(2) values mark individuals with low
      cerebral oxygen reserves and generally lower cognitive function; marginal awake
      rcSO(2) values that fall during sleep may indicate loss of cerebral oxygen
      reserve and an increased risk for cognitive decline. Further studies may clarify
      the significance of and mechanisms underlying individual differences in awake
      rcSO(2) and the changes that occur in rcSO(2) while asleep.

PMID- 21076088
TI  - Lifestyle consultation in general practice--the doctor's toolbox: a qualitative
      focus group study.
AB  - BACKGROUND: GPs consider individual lifestyle counselling as part of their
      obligation. There is a lack of knowledge about how such counselling is done.
      OBJECTIVE: To investigate what tools GPs utilize in individual consultations
      concerning lifestyle change. METHODS: Qualitative analysis of six focus groups
      with 50 GPs sharing and commenting each other's case stories. RESULTS: To enhance
      change of lifestyle, GPs adjusted the organization of their practice and utilized
      visualization tools. They established doctor-patient relationships based on
      shared decision making and trust, and gave their patients advice and tips to
      accomplish change, but also used paternalistic approaches and rhetoric
      manipulation. CONCLUSIONS: GPs use a variety of tools in consultations about
      lifestyle change. A patient-centred approach is shown, but GPs also deliberately
      use distressing communication tools.

PMID- 21076089
TI  - Breast cancer: comparative effectiveness of positron emission mammography and MR
      imaging in presurgical planning for the ipsilateral breast.
AB  - PURPOSE: To determine the performance of positron emission mammography (PEM), as
      compared with magnetic resonance (MR) imaging, including the effect on surgical
      management, in ipsilateral breasts with cancer. MATERIALS AND METHODS: Four
      hundred seventy-two women with newly diagnosed breast cancer who were offered
      breast-conserving surgery consented from September 2006 to November 2008 to
      participate in a multicenter institutional review board-approved, HIPAA-compliant
      protocol. Participants underwent contrast material-enhanced MR imaging and
      fluorine 18 fluorodeoxyglucose PEM in randomized order; resultant images were
      interpreted independently. Added biopsies and changes in surgical procedure for
      the ipsilateral breast were correlated with histopathologic findings. Performance
      characteristics were compared by using the McNemar test and generalized
      estimating equations. RESULTS: Three hundred eighty-eight women (median age, 58
      years; age range, 26-93 years; median estimated tumor size, 1.5 cm) completed the
      study. Additional cancers were found in 82 (21%) women (82 ipsilateral breasts;
      median tumor size, 0.7 cm). Twenty-eight (34%) of the 82 breasts were identified
      with both PEM and MR imaging; 21 (26%) breasts, with MR imaging only; 14 (17%)
      breasts, with PEM only; and seven (8.5%) breasts, with mammography and
      ultrasonography. Twelve (15%) cases of additional cancer were missed at all
      imaging examinations. Integration of PEM and MR imaging increased cancer
      detection-to 61 (74%) of 82 breasts versus 49 (60%) of 82 breasts identified with
      MR imaging alone (P < .001). Of 306 breasts without additional cancer, 279
      (91.2%) were correctly assessed with PEM compared with 264 (86.3%) that were
      correctly assessed with MR imaging (P = .03). The positive predictive value of
      biopsy prompted by PEM findings (47 [66%] of 71 cases) was higher than that of
      biopsy prompted by MR findings (61 [53%] of 116 cases) (P = .016). Of 116
      additional cancers, 61 (53%) were depicted by MR imaging and 47 (41%) were
      depicted by PEM (P = .043). Fifty-six (14%) of the 388 women required mastectomy:
      40 (71%) of these women were identified with MR imaging, and 20 (36%) were
      identified with PEM (P < .001). Eleven (2.8%) women underwent unnecessary
      mastectomy, which was prompted by only MR findings in five women, by only PEM
      findings in one, and by PEM and MR findings in five. Thirty-three (8.5%) women
      required wider excision: 24 (73%) of these women were identified with MR imaging,
      and 22 (67%) were identified with PEM. CONCLUSION: PEM and MR imaging had
      comparable breast-level sensitivity, although MR imaging had greater lesion-level
      sensitivity and more accurately depicted the need for mastectomy. PEM had greater
      specificity at the breast and lesion levels. Eighty-nine (23%) participants
      required more extensive surgery: 61 (69%) of these women were identified with MR
      imaging, and 41 (46%) were identified with PEM (P = .003). Fourteen (3.6%) women
      had tumors seen only at PEM.

PMID- 21076091
TI  - Evaluation of head-only electrical stunning for practical application: assessment
      of neural and meat quality parameters.
AB  - Behavioral and neural responses of 47 broilers to head-only single-bird
      electrical stunning were evaluated using cone-shaped restrainers in which the
      broilers were suspended by their feet. Meat quality assessment was performed on 2
      groups of 25 broilers stunned using the head-only method or a conventional water
      bath method. Hemorrhages were quantified by a visual grading system. On
      electroencephalogram recordings, a general epileptiform insult was observed when
      a set current of at least 190 mA (~100 V, 50 Hz) was applied for a duration of
      0.5, 3, or 5 s. This insult showed a tonic phase, followed by a clonic phase and
      an exhaustion phase, after which the birds recovered. On the basis of visual
      observation, these birds may have been unconscious for approximately 30, 44, or
      65 s. According to correlation dimension analysis scores, these durations were
      18, 12, and 16 s, respectively. Within a confidence limit of 95%, taking into
      account the number of birds with a reliable electroencephalogram, the chance of
      an effective stun lies between 0.95 and 1.00 with an average current of 190 +/-
      30 mA. After stunning, the electrocardiogram revealed fibrillation. The heart
      rate decreased significantly (P < 0.05) after stunning but recovered thereafter.
      The pH after chilling was (P < 0.05) lower in the group stunned head only
      compared with the water bath group. The percentages of fillets free of blood
      splashes were 80% in carcasses of head-only-stunned birds and 16% in carcasses
      from broilers stunned in the commercial water bath. It was concluded that
      broilers were insensible and unconscious after head-only electrical stunning
      using pin-electrodes. Because of the risk that broilers can rapidly regain
      consciousness after stunning, cutting the neck immediately after stunning is
      recommended. It is also recommended that the head-only equipment be developed
      further for practical application and commercial use.

PMID- 21076092
TI  - Different effects of infrared and one-half hot blade beak trimming on beak
      topography and growth.
AB  - This study examined the effects of infrared beak treatment (IR-BT) and hot blade
      beak trimming (HB-BT) on beak length and production in laying hen pullets.
      Seventy-two 1-d-old birds were randomly assigned to the HB-BT, IR-BT, or control
      group. Birds were pair housed by treatment, and beak images and production
      indices were obtained posttreatment at fixed intervals for 10 wk. Immediately
      after treatment, HB-BT beaks were shorter than control or IR-BT beaks (P < 0.01),
      whereas control and IR-BT beaks remained comparable in length until the onset of
      tissue degeneration and erosion of the IR-BT beaks at 1 to 2 wk posttreatment. At
      wk 2 posttreatment, beaks were longest in control birds, intermediate in IR-BT
      birds, and shortest in HB-BT birds (P < 0.01). Thereafter, an increase in beak
      length in all treatments was observed over time (P < 0.01), but HB-BT beaks had
      the greatest regrowth. The beak length of birds in the HB-BT group was similar to
      that of birds in the IR-BT group from wk 3 to 8, and then grew longer at wk 9 and
      10 posttreatment (P < 0.01). The effects of treatments on BW emerged at d 5
      posttreatment. The BW of birds in the HB-BT group was suppressed up to and
      including wk 9 posttreatment compared with that of control birds (P < 0.05) and
      was significantly lower than that of birds in the IR-BT group between 2 and 4 wk
      posttreatment (P < 0.05). Birds in the IR-BT group did not differ from control
      birds after wk 3 posttreatment (P < 0.05). By the final week of the study,
      differences in BW across treatments were no longer apparent (P > 0.05). For the
      most part, feed intake was higher in control birds, intermediate in birds in the
      IR-BT group, and lowest in birds in the HB-BT group until wk 9 posttreatment (P <
      0.05). Similarly, feed waste was generally higher in control birds and least in
      birds in the HB-BT group (P < 0.05). The IR-BT treatment appeared to be more
      effective at inhibiting beak regrowth, with a less pronounced effect on feed
      intake than the HB-BT treatment in laying hen pullets.

PMID- 21076093
TI  - Beak condition and cage density determine abundance and spatial distribution of
      northern fowl mites, Ornithonyssus sylviarum, and chicken body lice, Menacanthus
      stramineus, on caged laying hens.
AB  - Adult White Leghorn hens (Hy-Line strain W-36) were inoculated with either
      northern fowl mites or chicken body lice, and the ectoparasite populations were
      monitored over periods of 9 to 16 wk. Two beak conditions (beak trimmed or beak
      intact) and 2 housing densities (1 or 2 hens per 25 * 31 cm suspended wire cage)
      were tested. Populations of both ectoparasites were at least 10 times lower on
      beak-intact hens compared with populations on beak-trimmed hens. Cage density did
      not influence mite numbers, but higher numbers of lice (2 to 3 times) developed
      on hens held at the higher cage density. Louse distribution on the body and louse
      population age structure were also influenced by host beak condition. Beak-intact
      hens had a higher proportion of lice under the wings, whereas beak-trimmed hens
      had the majority of lice on the lower abdomen. Louse populations on beak-trimmed
      hens also comprised relatively more immature stages than populations found on
      beak-intact hens. The effects are likely related to decreased grooming efficiency
      by beak-trimmed hens and, in the case of lice, the higher host density. The high
      mite and louse populations on most commercial caged laying hens are probably a
      direct result of beak trimming. However, selection of more docile breeds that can
      be held without trimming may allow the hens themselves to reduce ectoparasites
      below economically damaging levels. This could benefit producers, animal welfare
      advocates, and human health by reducing 1) costs of beak trimming, 2) pesticide
      treatment costs (including human and bird chemical exposure concerns), and 3)
      objections to beak trimming from the animal welfare community.

PMID- 21076094
TI  - Association of Janus kinase 2 polymorphisms with growth and reproduction traits
      in chickens.
AB  - Growth and reproduction are 2 economically important traits in the poultry
      industry. Janus kinase 2 (JAK) participates in the JAK2/signal transducer and
      activator of transcription 5 growth hormone signaling pathway, which plays
      important roles in the processes of growth and reproduction. The present study
      was designed to investigate the association of JAK2 SNP and haplotypes with
      growth as well as with reproductive traits in chickens. Fourteen JAK2 SNP were
      identified by pooled DNA sequencing, and 5 of these were genotyped for 768
      Beijing You hens by using a matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry assay. For 5 growth traits, BW at 17 wk of age was
      significantly associated with JAK2 C28109928T and A28135099G (P < 0.05). The 2
      SNP were strongly related to BW at first egg, egg weight at first egg, and egg
      weight at 36 wk of age (P < 0.05). The SNP JAK2 C28122751T was found to be
      associated with BW at first egg and egg weight at 36 wk of age (P = 0.041 and P =
      0.046, respectively), whereas JAK2 G28132240C was related to egg number at 40 wk
      of age (P < 0.01). Further haplotype analyses showed that 4 haplotypes checked in
      the population had no distinct influence on growth traits but were associated
      with 7 reproductive traits, namely, age at first egg; BW at first egg; egg weight
      at first egg; egg weight at 36 wk of age; and egg numbers at 32, 36, and 40 wk of
      age (P < 0.05). The results indicated that the JAK2 polymorphisms could be
      potential molecular markers to improve laying performance and growth traits in
      chickens.

PMID- 21076095
TI  - Genetic diversity and population structure in lines of chickens divergently
      selected for high and low 8-week body weight.
AB  - A long-term selection experiment for high or low 8-wk BW in White Plymouth Rock
      chickens was conducted to study effects of selection on BW and correlated
      characters. Two lines [high (HWS), low (LWS) weight] were established and have
      undergone 48 generations of selection. The lines were managed to curtail
      inbreeding and to maintain similar population structures; such is necessary for
      equitable comparison of selection response between lines. Our objective was to
      test the success of that breeding strategy by characterizing genetic diversity
      and inbreeding in these lines. A pedigree of 5,998 individuals was assembled,
      with 68 founders, 2,962 HWS chickens, and 2,968 LWS chickens. Inbreeding
      coefficients (F) were calculated for each line. Maximum F was 0.53 and 0.61, mean
      F was 0.26 (SD 0.15) and 0.30 (SD 0.17), and change in F was 1.3 and 1.6% per
      generation in LWS and HWS lines, respectively. The effective population size was
      38.3 in LWS and 32.1 in HWS lines. The effective number of founders was 15.7 in
      both lines, and the effective number of ancestors was 17.5 and 15.5 in LWS and
      HWS lines, respectively. Thirty ancestors accounted for 90% of the genetic makeup
      of both lines. Seven male and eight female founders still contributed to both
      lines at generation 48, although some contributed more to one line than the
      other. Family sizes were similar for males and females of each line, with males
      having larger family sizes with greater variance. Accumulated inbreeding was high
      and effective population size was low, as expected in closed lines. Effective
      number of founders was relatively low compared with actual number of founders,
      indicating some contributed more than others to the last generation. Family size
      statistics indicated that fewer males than females were used, leading to the
      observed levels of inbreeding. Given their similarity in genetic diversity and
      family size, it can be concluded that breeding decisions throughout the project
      resulted in similar population structures in the lines.

PMID- 21076096
TI  - Efficacy of a bacteriophage isolated from chickens as a therapeutic agent for
      colibacillosis in broiler chickens.
AB  - The efficacy of bacteriophage EC1, a lytic bacteriophage, against Escherichia
      coli O78:K80, which causes colibacillosis in poultry, was determined in the
      present study. A total of 480 one-day-old birds were randomly assigned to 4
      treatments groups, each with 4 pens of 30 birds. Birds from the control groups
      (groups I and II) received PBS (pH 7.4) or 10(10) pfu of bacteriophage EC1,
      respectively. Group III consisted of birds challenged with 10(8) cfu of E. coli
      O78:K80 and treated with 10(10) pfu of bacteriophage EC1 at 2 h postinfection,
      whereas birds from group IV were challenged with 10(8) cfu of E. coli O78:K80
      only. All the materials were introduced into the birds by intratracheal
      inoculation. Based on the results of the present study, the infection was found
      to be less severe in the treated E. coli-challenged group. Mean total viable cell
      counts of E. coli identified on eosin methylene blue agar (designated EMB + E.
      coli) in the lungs were significantly lower in treated, E. coli-challenged birds
      than in untreated, E. coli-challenged birds on d 1 and 2 postinfection. The EMB +
      E. coli isolation frequency was also lower in treated birds; no E. coli was
      detectable in blood samples on any sampling day, and E. coli were isolated only
      in the liver, heart, and spleen of treated chickens at a ratio of 2/6, 1/6, and
      3/6, respectively, at d 1 postinfection. The BW of birds from the E. coli
      challenged group treated with bacteriophage EC1 were not significantly different
      from those of birds from both control groups but were 15.4% higher than those of
      the untreated, E. coli-challenged group on d 21 postinfection. The total
      mortality rate of birds during the 3-wk experimental period decreased from 83.3%
      in the untreated, E. coli-challenged birds (group IV) to 13.3% in birds treated
      with bacteriophage EC1 (group III). These results suggest that bacteriophage EC1
      is effective in vivo and could be used to treat colibacillosis in chickens.

PMID- 21076098
TI  - Effect of four processed animal proteins in the diet on digestibility and
      performance in laying hens.
AB  - An experiment was performed to investigate the effect of animal vs. vegetable
      protein sources in the diet of laying hens on the development of hen performance.
      A diet containing protein sources of only vegetable origin was compared with 4
      diets, each containing 1 of 4 processed animal proteins (PAP). Two PAP (Daka-58
      and Sonac-60) were classified as meat meals, and the remaining 2 (Daka-40 and
      Sonac-50) were classified as meat and bone meals. First, fecal digestibility of
      nutrients in the PAP was determined in Lohmann Brown layers. Hens (n = 132) were
      housed in 22 cages (6 hens/cage) and allotted to 5 dietary treatments. In the PAP
      diets (4 replicates/treatment), 100 g/kg of CP of animal origin was added,
      replacing soybean meal and corn (Zea mays) in the basal diet (6
      replicates/treatment). The PAP sources differed largely in chemical composition
      and digestibility coefficients. Energy content (AME(n)) varied from 1,817 (Daka
      40) to 3,107 kcal/kg (Sonac-60), and digestible lysine varied from 15.4 (Daka-40)
      to 28.3 g/kg (Sonac-50). Subsequently, the effect of a control diet (without PAP)
      vs. 4 PAP diets (50 g/kg of CP of animal origin from the same batches as used in
      the digestibility study) on performance was determined. All diets were isocaloric
      (AME(n) = 2,825 kcal/kg) and isonitrogenous (digestible lysine = 6.8 g/kg). Hens
      were housed in 40 floor pens (12 hens/pen, 8 pens/treatment) from 20 to 40 wk of
      age. Feed intake levels of the hens fed the meat and bone meal diets were reduced
      compared with those of hens fed the meat meal diets, whereas the feed intake
      level of hens fed the control diet was intermediate. Laying hen performance
      differed between treatments, being was most favorable for the Sonac-50 treatment
      and most adverse for the Daka-40 treatment. Differences in laying hen performance
      seemed to be related partly to differences in feed intake and corresponding amino
      acid intake.

PMID- 21076097
TI  - Immune responses to dietary beta-glucan in broiler chicks during an Eimeria
      challenge.
AB  - Escalating consumer concerns regarding pathogen resistance have placed the
      poultry industry under mounting pressure to eliminate the use of chemotherapeutic
      agents as feed additives. One possible alternative receiving increased attention
      is the use of immunomodulators such as beta-glucan. A study was conducted to
      investigate the effects of a yeast-derived beta-glucan (Auxoferm YGT) on broiler
      chick performance, lesion scores, and immune-related gene expression during a
      mixed Eimeria infection. Day-old chicks were fed diets containing 0, 0.02, or
      0.1% YGT. On d 8 posthatch, one-half of the replicate pens were challenged with a
      mixed inoculum of Eimeria acervulina, Eimeria maxima, and Eimeria tenella.
      Measurements were taken and samples collected on d 4, 10, 14, and 21 posthatch.
      Dietary supplementation had no effect on performance or mortality. On d 14, 3
      birds per pen (n = 24/treatment) were scored for intestinal coccidia lesions.
      Gross lesion severity was significantly reduced in birds supplemented with 0.1%
      YGT. On d 10, inducible nitric oxide synthase (iNOS) expression was downregulated
      in the jejunum of challenged birds fed 0.1% YGT. Expression of iNOS in the ileum
      was downregulated in the nonchallenged birds, but upregulated in the challenged
      birds fed 0.1% YGT on d 14. Interleukin (IL)-18 was upregulated in the jejunum of
      0.1% YGT-treated birds. Interferon (IFN)-gamma expression was decreased in
      challenged and nonchallenged birds fed 0.1% YGT. The IL-4 expression was
      downregulated in the nonchallenged birds with 0.1% YGT diet supplementation. The
      IL-13 and mucin-1 levels were also reduced due to beta-glucan supplementation.
      Mucin-2 expression was increased in the nonchallenged birds, but decreased in the
      infected birds fed 0.1% YGT. These results suggest that although Auxoferm YGT at
      doses of 0.02 and 0.1% does not influence performance, it significantly reduces
      lesion severity and is capable of altering immune-related gene expression
      profiles, favoring an enhanced T helper type-1 cell response during coccidiosis.

PMID- 21076099
TI  - Nutrient utilization and functionality of the anterior digestive tract caused by
      intermittent feeding and inclusion of whole wheat in diets for broiler chickens.
AB  - Two experiments were carried out to study the effect of intermittent feeding,
      diet structure, and their interaction on the performance, feeding pattern, and
      digestive adaptation of broiler chickens. In experiment 1, 40 Cobb broiler
      chickens were fed, either ad libitum or intermittently, a commercial starter diet
      diluted with 150 g/kg of ground or whole wheat in a 2 * 2 factorial arrangement.
      Ad libitum feeding consisted of continuous access to feed in a room with 18 h of
      light and 6 h of complete darkness, whereas birds on intermittent feeding had
      restricted access to feed from 7 d of age, with 4 one-hour feeding bouts/d and
      one 2-h feeding bout/d from d 14. No interaction was found between feed structure
      and feeding regimen for any of the measurements. Although BW gain was not
      significantly different among any of the treatments, birds given whole wheat or
      fed intermittently had significantly better feed efficiency than those given
      ground wheat and fed ad libitum. Inclusion of whole wheat instead of ground wheat
      also markedly increased (P < 0.001) the AME(n) value and fecal starch
      digestibility. In experiment 2, 60 Ross broiler chickens were trained to meal
      feeding on a wheat-based diet containing a commercial phytase, and 5 birds were
      killed every 15 min after having access to feed, to collect crop contents.
      Phytate was gradually degraded in the crop, with a 50% reduction in inositol 6
      phosphate after a 100-min retention time. In conclusion, these results indicate
      that broiler chickens have a remarkable ability to maintain growth rate during
      intermittent feeding because the crop is used as an intermediate storage organ,
      and that improvements in feed efficiency may occur, among others through
      increased efficacy of exogenous enzymes. Even though stimulation of the gizzard
      through a coarse feed structure improves feed efficiency, it does not appear to
      affect the ability of the bird to handle intermittent feeding.

PMID- 21076100
TI  - Standardized ileal amino acid digestibility in dry-extruded expelled soybean
      meal, extruded canola seed-pea, feather meal, and poultry by-product meal for
      broiler chickens.
AB  - Ileal digestibility of amino acids (AA) in dry-extruded expelled soybean meal
      (DESBM), co-extruded canola seed-pea blend (ECSP, 50:50 wt/wt basis), poultry by
      product meal (PBPM), and feather meal (FM) were determined in broiler chicks. For
      each ingredient, 5 samples each collected on different occasions were evaluated.
      Birds (n = 180 for each sample) were fed a commercial starter diet from d 1 to 15
      of age followed by the test diets from d 15 to 21. Dry-extruded expelled soybean
      meal, ECSP, PBPM, and FM were included in the test diets at 95.3, 95.3, 38.4, and
      28.4%, respectively, as the sole source of AA and balanced for minerals and
      vitamins. Chromic oxide (0.3%) was included in all diets as a digestibility
      marker. Each diet (5 per ingredient) was randomly assigned to 6 replicate cages,
      each with 6 birds. On d 21, birds were killed to collect ileal digesta for
      determining the apparent ileal AA digestibility on cage basis. The standardized
      ileal digestibility (SID) values were calculated using ileal endogenous AA losses
      previously determined in our laboratory. The apparent ileal digestibility of AA
      ranged from 78 to 91%, 68 to 83%, 51 to 81%, and 39 to 74% for DESBM, ECSP, PBPM,
      and FM, respectively. The respective ranges for SID values were 83 to 96%, 72 to
      85%, 58 to 86%, and 42 to 78%. Among the indispensable AA, the lowest SID was
      observed for Thr in all test ingredients, whereas the highest SID was observed
      for Phe except in ECSP in which Arg had the highest SID. The SID of Lys (CV) were
      91% (2.8%), 79% (2.0%), 78% (7.4%), and 60% (10%) for DESBM, ECSP, PBPM, and FM,
      respectively, whereas the SID of TSAA (CV) were 88% (4.5%), 77% (2.4%), 74%
      (9.0%), and 55% (18%), respectively. These SID AA data will help nutritionists to
      formulate broiler diets that more closely match the birds' requirements and
      minimize nutrient excess.

PMID- 21076101
TI  - Evaluation of the nutritional equivalency of soybean meal with the genetically
      modified trait DP-3O5423-1 when fed to laying hens.
AB  - An experiment using 336 Hy-Line W-36 Single Comb White Leghorn hens was conducted
      to evaluate transgenic soybeans containing the gm-fad2-1 gene fragment and the gm
      hra gene. Transcription of the gm-fad2-1 gene fragment results in an increased
      level of oleic acid (18:1) in the seed, and expression of the soybean
      acetolactate synthase protein (GM-HRA) encoded by the modified gm-hra gene, is
      used as a selectable marker during transformation. Pullets (20 wk of age) were
      placed in cage lots (7 hens/cage, 2 cages/lot) and were randomly assigned to 1 of
      4 corn-soybean meal dietary treatments (6 lots/treatment) formulated with the
      following soybean meals: nontransgenic near-isoline control (control),
      nontransgenic commercial reference soybean meal A (92M72), nontransgenic
      commercial reference soybean meal B (93B15), or transgenic soybean meal produced
      from soybeans containing event DP-3O5423-1 (305423). Weeks 20 to 24 were a
      preconditioning period, and the 4 experimental diets were then fed from 25 to 36
      wk of age. Differences between the 305423 and control group means were evaluated,
      with statistical significance at P < 0.05. Body weight, hen-day egg production,
      egg mass, feed consumption, and feed efficiency for hens fed the 305423 soybean
      meal were not significantly different from the respective values for hens fed
      diets formulated with the near-isoline soybean meal. Likewise, egg component
      weights, Haugh unit measures, and egg weights were similar regardless of the
      soybean meal source. This research indicates that performance of hens fed diets
      containing 305423 soybean meal, as measured by egg production and egg quality,
      was similar to that of hens fed diets formulated with the near-isoline control
      and commercial soybean meals.

PMID- 21076102
TI  - Influence of graded levels of brewers dried grains on pellet quality and
      performance in broiler chickens.
AB  - The aim of the current study was to evaluate the effect of a gradual substitution
      of wheat and soy with brewers dried grains (BDG) on pellet quality, performance,
      and organ weights in broiler chickens. Five diets were formulated in which 0, 10,
      20, 30, or 40% BDG replaced wheat and soy, with a concomitant gradual reduction
      in the calculated AME level. Each of the 5 experimental diets was fed to 12-d-old
      broiler chickens (Ross 308) kept in 6 pens, with 12 birds/pen. The birds had ad
      libitum access to feed and water until termination of the experiment at d 33.
      Feed intake was not affected by BDG inclusion and compensatory feed intake did
      not occur, perhaps having been neutralized by a significant (P < 0.001) reduction
      in the pellet durability index. The pellet durability index was 85% in the
      control diet (0% BDG) and decreased significantly (P < 0.001) to 68% in the diet
      with 40% BDG. Increased levels of BDG reduced BW gain significantly (P < 0.001)
      and led to a significant (P < 0.001) increase in the feed:gain ratio. The
      feed:gain ratio was significantly (P < 0.05) higher in birds fed 30 and 40% BDG
      compared with birds fed 0, 10, and 20% BDG. The apparent ileal digestibility
      values of protein and energy were significantly reduced by BDG inclusion (P <
      0.01 and P < 0.001, respectively), whereas starch digestibility increased
      significantly (P < 0.001). The relative gizzard weight increased significantly (P
      < 0.001), whereas the relative cecal weights were not affected by BDG inclusion.
      To conclude, 10 to 20% inclusion of BDG supports acceptable growth and feed
      utilization, and favors the development of a well-functioning gizzard.

PMID- 21076103
TI  - Improved hatchability and posthatch performance in turkey poults receiving a
      dextrin-iodinated casein solution in ovo.
AB  - Two experiments were conducted with a commercial turkey company using a
      commercial egg injection system to investigate the effect of a dextrin-iodinated
      casein solution injected in ovo at 25 d of incubation on turkey poult
      hatchability, hatch weight, and growth (6 or 7 d posthatch). In experiment 1, a
      total of 3,900 turkey eggs (1,300 per group) were injected at 25 d of incubation
      with either 200 MUL of a control (physiological saline) solution or a dextrin
      solution (18% maltodextrin and 10% potato starch dextrin) with 75 or 375 MUg/mL
      of iodinated casein (DexIC75 or DexIC375, where Dex and IC refer to dextrin and
      iodinated casein, respectively). Two hundred poults from each group were neck
      tagged, weighed (hatch weight), placed in a commercial turkey house within a
      single brooder ring, and weighed again (7 d posthatch). In experiment 2, a total
      of 5,200 eggs (2,600 per group) were injected with the control or DexIC75
      solution. A total of 600 poults (300 per group) were neck-tagged and hatch
      weights were obtained, followed by placement in a single brooder ring in a
      commercial house and a second weighing (6 d posthatch). Eggs in experiments 1 and
      2 were obtained from hen flocks that were 33 and 5 wk into the laying cycle,
      respectively. In experiment 1, the DexIC75 injection resulted in a 1.8% increase
      (P = 0.03) in hatch weight. In experiment 2, the DexIC75 treatment resulted in a
      2.4% increase in hatchability (P = 0.01), a 4.3% increase in hatch weight (P <
      0.001), and a 1.8% increase in 6-d poult weights (P < 0.03) compared with
      controls. Results of this study indicate that a solution containing dextrin and
      75 MUg/mL of iodinated casein injected into turkey eggs at 25 d of incubation may
      be used to improve early poult weights, hatchability, or both in commercial
      turkey production.

PMID- 21076104
TI  - Effects of divergent selection for 8-week body weight on postnatal enzyme
      activity pattern of 3 fiber types in fast muscles of male broilers (Gallus gallus
      domesticus).
AB  - A divergent selection experiment was conducted for 8-wk BW in chickens. At 3, 6,
      9, and 12 wk of age, samples of pectoralis profundus (PP) and biceps femoris (BF)
      muscles from fast-growing and slow-growing lines were used to estimate the enzyme
      activities and muscle fiber diameter. Microphotometric measurements made in situ
      of succinate dehydrogenase (SDH, EC 1.3.99.1) and glycerol-3-phosphate
      dehydrogenase (GPDH, EC 1.1.99.5) were completed on serial sections of PP and BF
      muscles from male chickens, in order to examine the ratio of SDH:GPDH activity in
      single fibers. On the basis of the SDH:GPDH activity ratios, muscle fibers were
      divided using cluster analysis into 3 populations of different fiber types (O =
      oxidative, OG = oxidative-glycolytic, and G = glycolytic). Cockerels of the SGL
      attained an 8.1-fold increase and those of the FGL a 6.8-fold increase in BW at
      12 wk compared with that at 3 wk of age. The O, OG, and G type fibers of the BF
      muscles of the SGL had significantly (P <= 0.001) lower SDH:GPDH activity ratios
      than those of the FGL. A step decrease in the SDH:GPDH activity of O, OG, and G
      fibers in the PP of both lines occurred, and this differed significantly between
      SGL and FGL (P <= 0.001). Age and line effects influenced the diameter of the 3
      fiber types in the BF muscle only. In contrast to this response, all 3 fiber
      types of the PP muscles reached similar diameters in both lines during the growth
      process from wk 3 to 12. From the results of this study, we concluded that the
      activities of metabolic enzymes in skeletal muscle fibers are under the influence
      of muscle type, age, and selection pressure. Microphotometry is a suitable method
      for the evaluation of enzyme activity measured in a single muscle fiber. The
      method enables precise estimation of enzyme activities, especially in muscles
      composed of populations of different metabolic fiber types.

PMID- 21076105
TI  - Changes in hepatic lipid parameters and hepatic messenger ribonucleic acid
      expression following estradiol administration in laying hens (Gallus domesticus).
AB  - Fatty liver hemorrhagic syndrome (FLHS) is characterized by increased hepatic
      triacylglycerol content associated with liver hemorrhages and results in a sudden
      decline in egg production. Genetic, environmental, nutritional, and hormonal
      factors have all been implicated in the etiology of FLHS, but the exact cause of
      FLHS is still unknown. Estrogens have been implicated in the development of
      excess fat content of the liver and in the etiology of FLHS. This study
      investigated estradiol (E(2)) administration in hens and its effect on lipid
      metabolism. Hy-Line Brown laying hens were intramuscularly injected with E(2) on
      a daily basis for 3 wk. The dosages were 0, 0.5, and 1.0 mg/kg of BW, with corn
      oil injections used as a control. Egg production and quality were measured among
      the groups, with no significant difference seen in egg production. Liver weights
      of hens treated with E(2) were greater than those of control hens, but the
      increase was not statistically significant. Serum glutamic-oxaloacetic
      transaminase and glutamic-pyruvic transaminase activities and E(2) plasma
      concentrations increased in a dose-dependent manner, with plasma concentration of
      E(2) increasing from 6,900 to 19,000 pg/mL. No significant differences in free
      cholesterol or phospholipids were observed, but there was a significant increase
      in hepatic triacylglycerol levels. Injection with E(2) showed an increased
      expression of mRNA for peroxisome proliferator-activated receptor gamma (23
      fold), but not for peroxisome proliferator-activated receptor alpha. A
      statistically significant increase was seen for fatty acid synthase,
      apolipoprotein B, and adenosine triphosphate citrate lyase, but not for acetyl
      coenzyme A carboxylase, apolipoprotein VLDL-II, microsomal triglyceride transport
      protein, or malic enzyme. For proteins involved in the oxidation of E(2), only
      cytochrome P450 3A37 showed a statistically significant increase. The present
      results suggest that E(2) upregulates the synthesis of fatty acids and
      triacylglycerols and the accumulation of hepatic lipids by increasing mRNA
      expression related to lipid metabolism, and that excess E(2) in the blood leads
      to activation of E(2) catabolic metabolism (cytochrome P450 3A37)-related mRNA
      expression.

PMID- 21076106
TI  - Effect of ambient temperature and light intensity on physiological reactions of
      heavy broiler chickens.
AB  - The effects of ambient temperature, light intensity, and their interaction on
      blood acid-base balance, metabolites, and electrolytes in broiler chickens under
      environmentally controlled conditions were examined in 2 trials. The experiment
      consisted of a factorial arrangement of treatments in a randomized complete block
      design. The 9 treatments consisted of 3 levels of temperatures (low = 15.6
      degrees C; moderate = 21.1 degrees C; high = 26.7 degrees C) from 21 to 56 d of
      age and 3 levels of light intensities (0.5, 3.0, 20 lx) from 8 to 56 d of age at
      50% RH. A total of 540 Ross 708 chicks were randomly distributed into 9
      environmentally controlled chambers (30 male and 30 female chicks/chamber) at 1 d
      of age. Feed and water were provided ad libitum. Venous blood samples were
      collected on d 21 (baseline), 28, 42, and 56. High ambient temperature
      significantly (P <= 0.05) reduced BW, partial pressure of CO(2), bicarbonate,
      hematocrit, hemoglobin, K(+), and Na(+) along with significantly (P <= 0.05)
      elevated pH level, Cl(-), glucose, osmolality, and anion gap concentrations.
      Partial pressure of O(2) was slightly increased in response to increased ambient
      temperature. There was no effect of light intensity on most of the blood
      variables examined. Acid-base regulation during high ambient temperature and
      light intensity exposure did not deteriorate despite a lower partial pressure of
      CO(2), which consequently increased blood pH because of a compensatory decrease
      in HCO(3)(-) concentration. Plasma corticosterone was not affected by
      temperature, light intensity, or their interaction. These results indicate that
      continuous exposure of broiler chickens to varying light intensities had a minor
      effect on physiological blood variables, whereas high ambient temperature
      markedly affected various blood variables without inducing stress in broilers.

PMID- 21076107
TI  - High- and low-temperature manipulation during late incubation: effects on
      embryonic development, the hatching process, and metabolism in broilers.
AB  - Temperatures continuously higher and lower than the standard incubation
      temperature by 3 degrees C from embryonic d 16 until embryonic d 18.5 result in
      differential effects on embryonic development, the hatching process, and
      embryonic metabolism. Embryos in the high-temperature group were forced into a
      state of malnutrition by the temperature treatment, as reflected by reduced
      embryo growth and yolk consumption, resulting in a significantly lower chick
      weight at hatch. In addition, altered air cell and blood gases as well as a
      retarded hatching process further indicated reduced growth of embryos exposed to
      higher incubation temperatures during the latter part of incubation. In addition,
      hatchability was significantly reduced by the high-temperature treatment due to
      higher embryonic mortality during the treatment period and the hatching process.
      Levels of blood glucose, lactate, liver glycogen, plasma triglycerides, and
      nonesterified fatty acids indicated an altered carbohydrate and lipid metabolism
      for the high-temperature group. Although the hatching process of embryos exposed
      to lower incubation temperatures was also significantly retarded, their embryonic
      development and growth were strikingly similar to those of the control group.

PMID- 21076108
TI  - Testosterone manipulation postcastration does not alter cloacal gland growth
      differences in male quail selected for divergent plasma corticosterone stress
      response.
AB  - Japanese quail selected for reduced (low-stress, LS) rather than exaggerated
      (high-stress, HS) plasma corticosterone response to brief restraint have
      consistently shown greater cloacal gland (CG) development, an androgen-dependent
      trait. In this study, the effects of testosterone implants on levels of plasma
      testosterone and CG development in castrated LS and HS quail were determined.
      Stress-line males were castrated and randomly allocated to 1 of 3 testosterone
      treatments: the empty testosterone (ET), low testosterone (LT), or high
      testosterone (HT) implant group. Cloacal gland volume was determined at 4 weekly
      intervals that represented ranges of 1 to 9 d, 8 to 17 d, 15 to 24 d, and 22 to
      31 d after castration and testosterone implantation. Levels of plasma
      testosterone were also assessed at the end of the study. Development of the CG
      was affected by quail line (LS > HS), testosterone treatment (HT > LT > ET), and
      time of measurement (1 to 9 d < 8 to 17 d < 15 to 24 d = 22 to 31 d after
      castration and testosterone implantation). A significant interaction between
      testosterone treatment and time of measurement on CG volume was also detected
      (with CG volume generally increasing with time in LT- and HT-treated quail, but
      not in ET-treated quail). However, even though HT implant treatments induced
      higher CG development than did LT treatments beyond the first interval of CG
      volume measurement, and despite the finding of greater CG volumes in LS than HS
      quail during the last 2 measurement intervals within each of the LT and HT
      groups, no interaction was observed between testosterone implant dosages and
      quail stress line on CG volume. Thus, by the end of the study, regardless of
      testosterone dose, CG volume was consistently greater in LS quail than in their
      HS counterparts. In addition, although, as expected, the testosterone implant
      treatment significantly altered levels of plasma testosterone (HT > LT > ET),
      neither quail line nor its interaction with testosterone treatment affected
      plasma testosterone. The present findings suggest that the often-observed
      depressed CG development in the HS line may be independent of testosterone
      effects.

PMID- 21076109
TI  - The assessment of viscosity measurements on the albumen of consumption eggs as an
      indicator for freshness.
AB  - Viscosity values of albumen reported in the literature are difficult to compare
      because different shear rates and different methods of sample preparation have
      been adopted. Therefore, we first investigated the effect of shear rate on the
      viscosity measurements of thick albumen. For intact albumen, a large intersample
      fluctuation in viscosity with increasing shear rate was observed. Furthermore, a
      large hysteresis effect was observed, indicating that the structural properties
      were substantially altered by the rotational behavior of the rotor. From this, we
      concluded that to obtain reliable measurements, the albumen needed to be mixed.
      After mixing, a smooth evolution in viscosity with increasing shear rate was
      observed. Compared with intact albumen, the hysteresis effect was smaller but
      still present. We next investigated the correlation between albumen viscosity and
      Haugh units. For this, we compared the viscosity of fresh eggs with the viscosity
      of eggs stored for 24 d at a temperature of 18 degrees C. The Haugh units were
      first determined, and the viscosity was next determined on mixed albumen at a
      shear rate of 200 rad/s. Mean viscosity equaled 0.0304 and 0.0181 Pa/s for fresh
      eggs and eggs stored for 24 d, respectively. The decrease in viscosity during
      storage was significant (alpha = 0.05). Furthermore, we observed that the
      correlation between Haugh units and viscosity measured on the same egg was low.
      Fresh eggs having comparable Haugh units differed substantially in their measured
      viscosities, whereas for stored eggs, the Haugh units differed substantially but
      the viscosities were comparable. It is unlikely that the very large variation in
      rheological properties observed among fresh eggs reflects the natural variation
      in albumen freshness present after lay. Results suggest that these differences
      were partly due to the structural changes caused by albumen sampling and by the
      turning motion of the rotor. We conclude that determination of the rheological
      properties of albumen is practically infeasible and that albumen viscosity cannot
      be used as an index for albumen freshness.

PMID- 21076110
TI  - Wines as possible meat marinade ingredients possess antimicrobial potential
      against Campylobacter.
AB  - This research studied the survival of high (7 log cfu/mL) and low (3 log cfu/mL)
      inoculum levels of Campylobacter in white and red wines and in grape and tomato
      juices, which could function as potential antimicrobial marinade ingredients. For
      comparison, survival was also studied in a commercial poultry meat marinade.
      White and red wines were shown to have very high bactericidal effects against
      Campylobacter. High counts were rapidly inactivated to undetectable numbers
      within 15 min in white wine and within 1 h in red wine, and low counts within 15
      min in white wine and within 30 min in red wine. By contrast, grape and tomato
      juices did not possess high bactericidal effects against Campylobacter because
      even low counts were occasionally detected after 48 h. The commercial marinade
      had rather high bactericidal effects against Campylobacter; the high counts were
      inactivated in most cases within 48 h, and all the low counts were inactivated
      within 3 h. When testing chicken meat inoculated with Campylobacter and
      subsequently submerged in white or red wine, the antibacterial activity of the
      wine was largely reduced. Wines lowered the Campylobacter load inoculated on
      chicken meat by approximately 1 log cfu/mL over 48 h. The results suggest that
      wines could be used as antimicrobial ingredients together with the addition of
      further antimicrobial agents in meat marinades to reduce the numbers of
      Campylobacter in naturally contaminated poultry products, thus lowering the risk
      of Campylobacter cross-contamination and transmission through food.

PMID- 21076111
TI  - Antioxidative effect of dietary Camelina meal in fresh, stored, or cooked broiler
      chicken meat.
AB  - Camelina sativa is an oilseed crop of the Brassica (Cruciferae) family that has
      gained increased popularity as a biofuel source. The present study was conducted
      to investigate the effects of feeding C. sativa meal to broiler birds on phenolic
      compounds, tocopherols, flavonoids, antioxidant capacity, and lipid peroxidation
      in chicken thigh meat during short (4 degrees C for 2 or 7 d) or long-term (-20
      degrees C for 90 d) storage and cooking. One hundred sixty 1-d-old Cobb chicks
      were fed a corn-soybean meal-based diet with added Camelina meal at 0% (control),
      2.5% (CAM2.5), 5% (CAM5), and 10% (CAM10). The experimental diets were fed for a
      period of 42 d. Feeding Camelina meal at 5 or 10% led to a 1.6-fold increase in
      gamma-tocopherols in the thigh meat when compared with control birds (P < 0.05).
      No effect of diet on gamma-tocopherols in the breast meat and alpha-tocopherols
      in the thigh and breast meat was observed (P > 0.05). Antioxidant activity
      measured as 2,2-azino-bis [3-ethylbenzo-thiazoline-6-sulfonic acid] radical
      scavenging capacity in the thigh meat from CAM2.5, CAM5, and CAM10 was higher
      than control birds (P < 0.05). In the breast meat, 2,2'-azino-bis (3-ethylbenzo
      thiazoline-6-sulfonic acid) diammonium salt radical scavenging capacity was
      highest in CAM10 (P < 0.05). Feeding Camelina meal at 5 or 10% led to reductions
      in thigh TBA reactive substances (TBARS) during short-term (2 d) and long-term
      storage (P < 0.05). The TBARS of thigh meat from CAM5 and CAM10 were reduced up
      to 49 or 36% during 2- or 90-d storage, respectively, when compared with control
      (P < 0.05). However, no effect of diet on thigh meat TBARS at 7 d of storage was
      observed among treatment groups. Overall, TBARS were highest in the thigh meat
      from control and CAM2.5 birds (P < 0.05). Upon cooking, TBARS were lowest in
      thigh meat from CAM10 birds, which was over 48% lower than in meat from birds fed
      the control diet (P < 0.05). The current study showed that Camelina meal could be
      effective in inhibiting lipid oxidation and enhancing antioxidant capacity.
      However, the effect was more prominent in the thigh than breast meat.

PMID- 21076112
TI  - Changes in selected biochemical indices related to transport of broilers to
      slaughterhouse under different ambient temperatures.
AB  - The effect of transport distance on selected biochemical parameters
      (corticosterone, uric acid, triglycerides, total protein, glucose, and lactate)
      under various ambient temperatures was monitored in a group of unsexed Ross 308
      broilers aged 42 d. Broilers were transported to the slaughterhouse over 3
      different travel distances (10, 70, and 130 km). They were sampled before and
      after each transportation in 3 various periods with different ambient
      temperatures (-5 to +5 degrees C, 10 to 20 degrees C, and 25 to 35 degrees C),
      which approximately correspond to temperature conditions during transport in
      individual seasons of the year (winter, fall, summer). The changes in biochemical
      parameters were specific in their dependence on the travel distance and the
      ambient temperature under which the broilers were transported. The highest
      corticosterone concentration was found in broilers before transport (i.e.,
      immediately after catching, crating, and loading) at all ambient temperatures.
      The concentration of corticosterone was higher at winter temperatures than at
      summer and fall temperatures. Triglycerides decreased with travel distance,
      although this effect was detected under summer temperatures only. The
      concentration of total protein was higher only after 10 km of transport and then
      it decreased with travel distance at all monitored ambient temperatures. A highly
      significant decrease (P < 0.01) in the glucose level of broilers was observed
      after 130 km of transport when compared with broilers before transport at fall
      and winter temperatures. The effect of travel distance on lactate concentrations
      was the same at all monitored ambient temperatures, with the lactate level
      decreasing with travel distance. The results obtained indicate that pretransport
      handling procedures (catching, crating, and loading) may be more stressful for
      broilers than the transport itself. To improve broiler meat quality, it is
      necessary to meet the need for broilers to recover before being slaughtered. With
      regard to different seasons of the year, we can assume that transport under
      conditions of low ambient temperatures in winter represents a more stressful
      event than transport during fall and summer.

PMID- 21076113
TI  - Dietary lipid source and vitamin E effect on lipid oxidation stability of
      refrigerated fresh and cooked chicken meat.
AB  - The fatty acid composition of chicken muscle may affect the lipid oxidation
      stability of the meat, particularly when subjecting the meat to thermal
      processing and storage. The objective of this study was to evaluate the diet
      effect on lipid oxidation stability of fresh and cooked chicken meat. Six hundred
      broilers were raised for a 6-wk feeding period and were assigned to 8 treatments
      with 3 repetitions. Broilers were fed a basal corn-soybean meal diet, including
      5% of either animal-vegetable, lard, palm kernel, or soybean (SB) oil, each
      supplemented with a low (33 mg/kg) or high (200 to 400 mg/kg) level of vitamin E.
      Fresh breast and thigh meat and skin were packaged and refrigerated (4 degrees C)
      for 15 d. Breast and thigh meat were frozen (-20 degrees C) and stored for ~6 mo
      and then thawed, deboned, ground, and formed into patties of 150 g each. Patties
      were cooked (74 degrees C), cooled, packaged, and stored in refrigeration for 6
      d. The lipid oxidation development of the products was determined using the TBA
      reactive substances analysis. The results showed that the lipid oxidation
      development, in both fresh chicken parts and cooked meat patties, was influenced
      by the interaction of either dietary lipid source or vitamin E level with storage
      time. Fresh breast meat showed no susceptibility to lipid oxidation, but thigh
      meat and skin presented higher (P < 0.05) malonaldehyde values in the SB oil
      treatment, starting at d 10 of storage. In cooked patties, during the entire
      storage time, the SB oil showed the highest (P < 0.05) lipid oxidation
      development compared with the other treatments. Regarding vitamin E, in both
      fresh parts and cooked meat patties, in most sampling days the high supplemented
      level showed lower (P < 0.05) malonaldehyde values than the control treatment. In
      conclusion, the lipid oxidation stability of chicken meat is influenced by the
      lipid source and vitamin E level included in the diet upon storage time and
      processing of the meat.

PMID- 21076114
TI  - Hatching egg characteristics, chick quality, and broiler performance at 2 breeder
      flock ages and from 3 egg weights.
AB  - The objective of this study was to determine the effects of flock age and egg
      weight on hatching egg characteristics, fertility, hatchability, salable chick
      production, and broiler performance using a commercial Cobb 500 broiler breeder
      flock. Hatching eggs from the same breeder flock in 3 weight categories (light,
      average, and heavy) were obtained from a commercial hatchery when the birds were
      29 and 59 wk of age. One group of eggs per age and weight category was selected
      to assess specific gravity and was broken open to weigh egg components. Another
      group of eggs was incubated for 21.5 d and incubation parameters were measured.
      At hatching, all salable chicks were individually weighed and placed in floor
      pens, where they were grown out for 41 d. Daily mortality, weekly feed
      consumption, and individual BW at 21 and 41 d were recorded. Irrespective of
      flock age and egg weight, all eggs had a specific gravity lower than 1.080, the
      commercial set value. Eggs from the young flock age had a smaller proportion of
      yolk and a greater proportion of albumen. Age affected fertility, with a lower
      value observed at 29 wk of age. Chicks from the flock at 59 wk hatched earlier
      than chicks from the flock at 29 wk, and light eggs hatched earlier than both
      average and heavy eggs. Broilers from the 29-wk-old breeders had a lower final BW
      than broilers from the 59-wk-old breeders. The smaller proportion of yolk in eggs
      from 29-wk-old broiler breeders may be associated with the low final BW observed
      in their offspring. This could mean that chicks hatching from young broiler
      breeders, which produce eggs with small yolks, may be at a disadvantage when
      reared under the same conditions as chicks produced by older broiler breeders
      whose eggs have larger yolks.

PMID- 21076115
TI  - Field study on effects of a heat exchanger on broiler performance, energy use,
      and calculated carbon dioxide emission at commercial broiler farms, and the
      experiences of farmers using a heat exchanger.
AB  - In broiler houses, ventilation removes moisture and maintains ambient temperature
      and air quality. During cold weather conditions, ventilation can result in
      undesirable heat loss from the house. Extra input of energy for heating the
      building is needed then, resulting in extra CO(2) emissions when fossil fuels are
      used for this purpose. In such a situation, an air-to-air heat exchanger (HE)
      might be valuable because it recovers heat by prewarming fresh supply air with
      warm inside air. The aim of this study was to analyze effects of on-farm use of
      an HE on broiler performance, energy use, and CO(2) emission by comparing
      production cycles with and without an HE, and to inventory the experiences of
      farmers using an HE. Data were collected of production cycles finished with (102)
      or without (149) an HE on 25 farms. Data on mortality, feed intake, water intake,
      and BW gain were obtained to analyze broiler performance. When available, gas and
      electricity use were obtained to analyze energy use and to calculate CO(2)
      emission. Farmers were interviewed about their experiences regarding the HE. The
      use of an HE tended to increase daily weight gain (56 vs. 55, SEM 0.3 g/d; P =
      0.07), but did not affect other performance variables. Based on 13 farms, gas use
      was reduced by 38% (P < 0.01) after installing an HE. Based on 3 farms only, an
      HE did not affect electricity use, total energy use, or calculated CO(2)
      emission. It appeared that farmers were satisfied with the HE because they
      experienced an increase in job satisfaction, an improvement of climate conditions
      and litter quality in the broiler house, and a more uniform temperature and
      broiler distribution in the house. We concluded that the use of an HE reduced gas
      use and has the ability to improve broiler weight gain but had no effect on other
      broiler performance variables. Effects on CO(2) emission were unclear. Farmers
      appeared to be positive about using an HE, because it improved broiler house
      climate and job satisfaction.

PMID- 21076118
TI  - Examining smoking behaviours among parents from the UK Millennium Cohort Study
      after the smoke-free legislation in Scotland.
AB  - OBJECTIVES: To investigate parental smoking behaviours between England and
      Scotland after the smoke-free legislation in Scotland came into effect in 2006
      and examine inequalities in maternal smoking behaviours between countries.
      METHODS: 5954 white mothers and 3757 fathers resident in England and 1522 white
      mothers and 904 fathers resident in Scotland who participated in the Millennium
      Cohort Study (a prospective nationally representative cohort study) when the
      cohort child was age 9 months (before legislation) and 5 years (after legislation
      in Scotland but not in England). The main outcome measures were smoking at 9
      months and 5 years, quitting smoking by 5 years, starting smoking by 5 years.
      RESULTS: In England and Scotland approximately 30% of parents reported smoking at
      9 months with only a slight decrease in smoking at 5 years. There were no
      differences between countries in parental smoking after the smoke-free
      legislation in Scotland came into effect, taking into account prior smoking
      levels. Light smokers (1-9 cigarettes/day) from Scotland were less likely to quit
      by 5 years than those from England, but there were no differences between
      countries among heavy smokers (10+ cigarettes/day). Non-smoking mothers from
      Scotland (6.2%) were less likely to start smoking by 5 years than mothers from
      England (7.3%). Mothers from more disadvantaged circumstances in both countries
      were more likely to report that they smoked or started smoking. In England
      quitting was also socially patterned, but in Scotland, after the legislation was
      introduced, the gradients in quitting smoking were flatter across social groups.
      CONCLUSIONS: Smoking behaviours among parents with young children remained
      relatively stable, highlighting the need for additional tobacco control efforts
      to support smoking cessation. However, the smoke-free legislation does not appear
      to widen health inequalities and may even help reduce them by encouraging
      quitting across socioeconomic groups.

PMID- 21076119
TI  - Unsupported planar lipid membranes formed from mycolic acids of Mycobacterium
      tuberculosis.
AB  - The cell wall of mycobacteria includes a thick, robust, and highly impermeable
      outer membrane made from long-chain mycolic acids. These outer membranes form a
      primary layer of protection for mycobacteria and directly contribute to the
      virulence of diseases such as tuberculosis and leprosy. We have formed in vitro
      planar membranes using pure mycolic acids on circular apertures 20 to 90 MUm in
      diameter. We find these membranes to be long lived and highly resistant to
      irreversible electroporation, demonstrating their general strength. Insertion of
      the outer membrane channel MspA into the membranes was observed indicating that
      the artificial mycolic acid membranes are suitable for controlled studies of the
      mycobacterial outer membrane and can be used in nanopore DNA translocation
      experiments.

PMID- 21076120
TI  - Head and neck tumor cell radiation response occurs in the presence of IGF1.
AB  - Radiation therapy for head and neck cancer results in severe secondary side
      effects in salivary glands. We previously demonstrated that the administration of
      IGF1 preserves or restores salivary gland function following radiation. Based on
      these findings, we propose to study the effect of IGF1 on human head and neck
      carcinoma cells. Head and neck tumor cells treated with radiation have
      significant reductions in tumor cell survival, as measured by MTT and crystal
      violet assays, regardless of IGF1 pre-treatment. Head and neck squamous carcinoma
      cell xenografts treated with concurrent radiation+IGF1 also exhibit significant
      tumor growth delay; however, growth rates are elevated compared with those in
      irradiated xenografts. In contrast, administration of IGF1 after radiation
      treatment has no effect on tumor xenograft growth rates. Analysis of these data
      suggests that localized delivery may be required for concurrent therapy to
      prevent secondary side-effects of radiotherapy, while post-therapy administration
      of IGF1 could be considered for the restoration of salivary function.

PMID- 21076121
TI  - Mouse mandible contains distinctive mesenchymal stem cells.
AB  - Although human orofacial bone-marrow-derived mesenchymal stem cells showed
      differentiation traits distinctly different from those of mesenchymal stem cells
      (MSCs) derived from long bone marrow (BMMSCs), mouse MSCs derived from orofacial
      bone have not been isolated due to technical difficulties, which in turn
      precludes the use of mouse models to study and cure orofacial diseases. In this
      study, we developed techniques to isolate and expand mouse orofacial bone/bone
      marrow-derived MSCs (OMSCs) from mandibles and verified their MSC characteristics
      by single-colony formation, multi-lineage differentiation, and in vivo tissue
      regeneration. Activated T-lymphocytes impaired OMSCs via the Fas/Fas ligand
      pathway, as occurs in BMMSCs. Furthermore, we found that OMSCs are distinct from
      BMMSCs with respect to regulating T-lymphocyte survival and proliferation.
      Analysis of our data suggests that OMSCs are a unique population of MSCs and play
      an important role in systemic immunity. ABBREVIATIONS: BMMSC, bone marrow
      mesenchymal stem cell; HA/TCP, hydroxyapatite/tricalcium phosphate; OMSC,
      orofacial mesenchymal stem cell; OVX, ovariectomized.

PMID- 21076122
TI  - Histatin 1 resists proteolytic degradation when adsorbed to hydroxyapatite.
AB  - Histatins are salivary proteins that exhibit a high affinity for hydroxyapatite
      and contribute to the acquired enamel pellicle. Previous studies have observed
      that, despite the high proteolytic activity in saliva, significant numbers of
      histatin molecules in acquired enamel pellicle are intact. Our working hypothesis
      was that histatins are less susceptible to proteinases present in saliva when
      adsorbed on the hydroxyapatite. To test this premise, we incubated histatin 1
      with hydroxyapatite and human whole saliva. Proteolytic products of this
      incubation were then characterized by PAGE, HPLC, and mass spectrometry. This
      study shows for the first time that binding to hydroxyapatite confers intact
      histatin 1 with resistance to proteolytic degradation.

PMID- 21076123
TI  - Hydrogen sulfide: advances in understanding human toxicity.
AB  - Hydrogen sulfide is a relatively common, frequently lethal, and unique
      occupational hazard for which research since 1990 has uncovered many anomalies
      and subtleties and a previously unsuspected physiological role for the endogenous
      agent. The result has been uncertainty and misunderstanding, particularly for
      persons new to the literature. This review addresses evidence that settles past
      controversies, guides practical issues in evaluating human toxicity, addresses
      unresolved issues involving chronic exposure, and points the way to a deeper
      understanding of the agent and its effects.

PMID- 21076124
TI  - Quantitative troponin and death, cardiogenic shock, cardiac arrest and new heart
      failure in patients with non-ST-segment elevation acute coronary syndromes (NSTE
      ACS): insights from the Global Registry of Acute Coronary Events.
AB  - BACKGROUND: The objective of this study was to determine if the extent of
      quantitative troponin elevation predicted mortality as well as in-hospital
      complications of cardiac arrest, new heart failure and cardiogenic shock. DESIGN:
      16,318 patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS)
      from the Global Registry of Acute Coronary Events (GRACE) were included. The
      maximum 24 h troponin value as a multiple of the local laboratory upper limit of
      normal was used. The population was divided into five groups based on the degree
      of troponin elevation, and outcomes were compared. An adjusted analysis was
      performed using quantitative troponin as a continuous variable with adjustment
      for known prognostic variables. RESULTS: For each approximate 10-fold increase in
      the troponin ratio, there was an associated increase in cardiac arrest, sustained
      ventricular tachycardia (VT) or ventricular fibrillation (VF) (1.0, 2.4, 3.4, 5.9
      and 13.4%; p<0.001 for linear trend), cardiogenic shock (0.5, 1.4, 2.0, 4.4 and
      12.7%; p<0.001), new heart failure (2.5, 5.1, 7.4, 11.6 and 15.8%; p<0.001) and
      mortality (0.8, 2.2, 3.0, 5.3 and 14.0%; p<0.001). These findings were replicated
      using the troponin ratio as a continuous variable and adjusting for covariates
      (cardiac arrest, sustained VT or VF, OR 1.56, 95% CI 1.39 to 1.74; cardiogenic
      shock, OR 1.87, 95% CI 1.61 to 2.18; and new heart failure, OR 1.57, 95% CI 1.45
      to 1.71). The degree of troponin elevation was predictive of early mortality (HR
      1.61, 95% CI 1.44 to 1.81; p<0.001 for days 0-14) and longer term mortality (HR
      1.18, 95% CI 1.07 to 1.30, p=0.001 for days 15-180). CONCLUSION: The extent of
      troponin elevation is an independent predictor of morbidity and mortality.

PMID- 21076125
TI  - Sphingomyelin induces cathepsin D-mediated apoptosis in intestinal epithelial
      cells and increases inflammation in DSS colitis.
AB  - BACKGROUND: The sphingolipid sphingomyelin is a constituent in food derived from
      animals. Digestive breakdown of sphingomyelin results in ceramide, recently
      suggested to be involved in activation of cathepsin D as a novel mediator of
      apoptosis. Damage of the epithelial barrier was detected in patients with
      inflammatory bowel disease (IBD) due to increased rates of intestinal epithelial
      cell (IEC) apoptosis. METHODS: Acute colitis was induced in C57-BL/6 mice with
      2.0% dextran sulfate sodium (DSS) over 7 days. Spontaneous colitis was developed
      in B6-IL10tm1Cgn (interleukin 10-negative (IL-10(-/-))) mice. Mice received 4 or
      8 mg sphingomyelin/day by oral gavage. IECs were isolated ex vivo. Apoptosis was
      determined by propidium iodide (PI) and terminal deoxynucleotidyl transferase
      dUTP nick end labelling (TUNEL) staining. Execution of apoptosis was confirmed by
      analysis of active cathepsin D, caspase-3 and caspase-9 with western blot and
      immunohistochemistry (IHC). RESULTS: Following DSS-mediated colitis, fluorescence
      activated cell sorting (FACS) analysis indicated increased apoptosis of IECs
      under dietary sphingomyelin. The mean sub-G(1) portion increased from 8.7+/-2.5%
      under a normal diet to 14.0+/-3.1% under dietary sphingomyelin. Cathepsin
      activity was significantly increased in isolated IECs after gavage of 4 mg of
      sphingomyelin per day. Western blot and IHC revealed execution of the apoptotic
      cascade via activated caspase-3 and caspase-9. Dietary sphingomyelin in the IL
      10(-/-) model confirmed aggravation of mucosal inflammation. CONCLUSION:
      Apoptosis of IEC induced by dietary sphingomyelin is mediated via ceramide and
      cathepsin D activation. This shortens the physiological life cycle of IECs and
      impairs crucial functions of the intestinal mucosa: barrier, defence and nutrient
      absorption. The findings provide evidence that dietary sphingomyelin may increase
      intestinal inflammation.

PMID- 21076127
TI  - Pragmatic trials in primary health care: what, when and how?

PMID- 21076126
TI  - Depletion of luminal iron alters the gut microbiota and prevents Crohn's disease
      like ileitis.
AB  - BACKGROUND: Iron replacement therapy is a common treatment in patients with
      anaemia and Crohn's disease, but oral iron supplements are less tolerated. The
      pathogenesis of Crohn's disease is attributed to intestinal bacteria and
      environmental factors that trigger disease in a genetically predisposed host. The
      aim of this study was to characterise the interrelationship between luminal iron
      sulfate, systemic iron, the gut microbiota and the development of chronic ileitis
      in a murine model of Crohn's disease. METHODS: Wild type (WT) and heterozygous
      TNF(DeltaARE/WT) mice were fed with an iron sulfate containing or iron sulfate
      free diet in combination with intraperitoneal control injections or iron
      injections for 11 weeks. RESULTS: TNF(DeltaARE/WT) mice develop severe
      inflammation of the distal ileum but remained completely healthy when transferred
      to an iron sulfate free diet, even if iron was systemically repleted. Absence of
      luminal iron sulfate reduced cellular markers of endoplasmic reticulum (ER)
      stress responses and pro-apoptotic mechanisms in the ileal epithelium. Phenotype
      or reactivity of major effector intraepithelial CD8alphabeta(+) T cells were not
      altered in the absence of luminal iron. Interestingly, ER stress mechanisms
      sensitised the small intestinal epithelial cell (IEC) line Mode-K to cytotoxic
      function of effector T cells from TNF(ARE/WT) mice. Pyrosequencing of 16S rRNA
      tags of the caecal microbiota revealed that depletion of luminal iron sulfate
      induced significant compositional alterations, while total microbial diversity
      (Shannon's diversity index) and number of total operational taxonomic units were
      not affected. CONCLUSION: This study showed that an iron sulfate free diet in
      combination with systemic iron repletion prevents the development of chronic
      ileitis in a murine model of Crohn's disease. Luminal iron may directly affect
      IEC function or generate a pathological milieu in the intestine that triggers
      epithelial cell stress-associated apoptosis through changes in microbial
      homeostasis. These results suggest that oral replacement therapy with iron
      sulfate may trigger inflammatory processes associated with progression of Crohn's
      disease-like ileitis.

PMID- 21076128
TI  - A brief culturally tailored intervention for Puerto Ricans with type 2 diabetes.
AB  - The information-motivation-behavioral skills (IMB) model of health behavior
      change informed the design of a brief, culturally tailored diabetes self-care
      intervention for Puerto Ricans with type 2 diabetes. Participants (n = 118) were
      recruited from an outpatient, primary care clinic at an urban hospital in the
      northeast United States. ANCOVA models evaluated intervention effects on food
      label reading, diet adherence, physical activity, and glycemic control (HbA1c).
      At follow-up, the intervention group was reading food labels and adhering to diet
      recommendations significantly more than the control group. Although the mean
      HbA1c values decreased in both groups ( INTERVENTION: 0.48% vs. CONTROL: 0.27%
      absolute decrease), only the intervention group showed a significant improvement
      from baseline to follow-up (p < .008), corroborating improvements in diabetes
      self-care behaviors. Findings support the use of the IMB model to culturally
      tailor diabetes interventions and to enhance patients' knowledge, motivation, and
      behavior skills needed for self-care.

PMID- 21076129
TI  - Incorporation and remobilization of 13C within the fine-root systems of
      individual Abies alba trees in a temperate coniferous stand.
AB  - Forest ecosystems have a large carbon (C) storage capacity, which depends on
      their productivity and the residence time of C. Therefore, the time interval
      between C assimilation and its return to the atmosphere is an important parameter
      for determining C storage. Especially fine roots (<=2 mm in diameter) undergo
      constant replacement and provide a large biomass input to the soil. In this
      study, we aimed to determine the residence time of C in living fine roots and the
      decomposition rates of dead fine roots. Therefore, we pulse-labelled nine 20-year
      old individual silver fir trees (Abies alba Miller; ~70 cm tall) with 13CO2 in
      situ to trace the assimilated C over time into the fine-root systems. Whole trees
      were harvested at different time points after labelling in autumn, biomass was
      determined and cellulose and starch of fine roots were extracted. Moreover, soil
      cores were taken and ingrowth cores installed, in which fine roots were
      genetically identified, to assess incorporation and remobilization of 13C in the
      fine roots of silver fir trees; litterbags were used to determine fine-root
      decomposition rates. The 13C label was incorporated in the fine-root system as
      cellulose within 3 days, with highest values after 30 days, before reaching
      background levels after 1 year. The highest delta13C values were found in starch
      throughout the experiment. 13C recovery and carbon mean residence times did not
      differ significantly among fine-root diameter classes, indicating size
      independent C turnover times in fine roots of A. alba trees of ~219 days.
      Furthermore, carbon was remobilized from starch into newly grown fine roots in
      the next spring after our autumn labelling. One year after installation,
      litterbags with fine roots revealed a decrease of biomass of ~40% with relative
      13C content in fine-root bulk biomass and cellulose of ~50%, indicating a faster
      loss of 13C-labelled compounds compared with bulk biomass. Our results also
      suggest that genetic analysis of fine-root fragments found in soil and ingrowth
      cores is advisable when working in mixed forest stands with trees of similar fine
      root morphology. Only then can one avoid dilution of the labelling signal by
      mistake, due to analysis of non-labelled non-target species roots.

PMID- 21076130
TI  - Homeopathy, non-specific effects and good medicine.

PMID- 21076131
TI  - Homeopathy has clinical benefits in rheumatoid arthritis patients that are
      attributable to the consultation process but not the homeopathic remedy: a
      randomized controlled clinical trial.
AB  - OBJECTIVES: To assess whether any benefits from adjunctive homeopathic
      intervention in patients with RA are due to the homeopathic consultation,
      homeopathic remedies or both. METHODS: Exploratory double-blind, randomized
      placebo-controlled trial conducted from January 2008 to July 2008, in patients
      with active stable RA receiving conventional therapy. Eighty-three participants
      from three secondary care UK outpatient clinics were randomized to 24 weeks of
      treatment with either homeopathic consultation (further randomized to
      individualized homeopathy, complex homeopathy or placebo) or non-homeopathic
      consultation (further randomized to complex homeopathy or placebo). Co-primary
      outcomes: ACR 20% improvement (ACR20) criteria and patient monthly global
      assessment (GA). SECONDARY OUTCOMES: 28-joint DAS (DAS-28), tender and swollen
      joint count, disease severity, pain, weekly patient and physician GA and pain,
      and inflammatory markers. RESULTS: Fifty-six completed treatment phase. No
      significant differences were observed for either primary outcome. There was no
      clear effect due to remedy type. Receiving a homeopathic consultation
      significantly improved DAS-28 [mean difference 0.623; 95% CI 0.1860, 1.060; P =
      0.005; effect size (ES) 0.70], swollen joint count (mean difference 3.04; 95% CI
      1.055, 5.030; P = 0.003; ES 0.83), current pain (mean difference 9.12; 95% CI
      0.521, 17.718; P = 0.038; ES 0.48), weekly pain (mean difference 6.017; 95% CI
      0.140, 11.894; P = 0.045; ES 0.30), weekly patient GA (mean difference 6.260; 95%
      CI 0.411, 12.169; P = 0.036; ES 0.31) and negative mood (mean difference - 4.497;
      95% CI -8.071, -0.923; P = 0.015; ES 0.90). CONCLUSION: Homeopathic consultations
      but not homeopathic remedies are associated with clinically relevant benefits for
      patients with active but relatively stable RA. TRIAL REGISTRATION: Current
      controlled trials, http://www.controlled-trials.com/, ISRCTN09712705.

PMID- 21076133
TI  - Extraordinary conservation, gene loss, and positive selection in the evolution of
      an ancient neurotoxin.
AB  - The recent determination of the genetic basis for the biosynthesis of the
      neurotoxin, saxitoxin, produced by cyanobacteria, has revealed a highly complex
      sequence of reactions, involving over 30 biosynthetic steps encoded by up to 26
      genes clustered at one genomic locus, sxt. Insights into evolutionary-ecological
      processes have been found through the study of such secondary metabolites because
      they consist of a measurable phenotype with clear ecological consequences,
      synthesized by known genes in a small number of species. However, the processes
      involved in and timing of the divergence of prokaryotic secondary metabolites
      have been difficult to determine due to their antiquity and the possible
      frequency of horizontal gene transfer and homologous recombination. Through
      analyses of gene synteny, phylogenies of individual genes, and analyses of
      recombination and selection, we identified the evolutionary processes of this
      cluster in five species of cyanobacteria. Here, we provide evidence that the sxt
      cluster appears to have been largely vertically inherited and was therefore
      likely present early in the divergence of the Nostocales, at least 2,100 Ma, the
      earliest reliably dated appearance of a secondary metabolite. The sxt cluster has
      been extraordinarily conserved through stabilizing selection. Genes have been
      lost and rearranged, have undergone intra- and interspecific recombination, and
      have been subject to duplication followed by positive selection along the
      duplicated lineage, with likely consequences for the toxin analogues produced.
      Several hypotheses exist as to the ecophysiological role of saxitoxin: as a
      method of chemical defense, cellular nitrogen storage, DNA metabolism, or
      chemical signaling. The antiquity of this gene cluster indicates that potassium
      channels, not sodium channels, may have been the original targets of this
      compound. The extraordinary conservation of the machinery for saxitoxin
      synthesis, under radically changing environmental conditions, shows that it has
      continued to play an important adaptive role in some cyanobacteria.

PMID- 21076134
TI  - Non-invasive aneuploidy detection using free fetal DNA and RNA in maternal
      plasma: recent progress and future possibilities.
AB  - BACKGROUND: Cell-free fetal DNA (cff DNA) and RNA can be detected in maternal
      plasma and used for non-invasive prenatal diagnostics. Recent technical advances
      have led to a drastic change in the clinical applicability and potential uses of
      free fetal DNA and RNA. This review summarizes the latest clinical developments
      in non-invasive prenatal diagnosis in the context of the latest technical
      developments. METHODS: We searched PubMed with the search terms 'prenatal', 'non
      invasive', 'fetal DNA', 'mRNA' and cross-referenced them with 'diagnostics',
      'microRNA', 'aneuploidy', 'trisomy' and 'placenta'. We also searched the
      reference list of the articles identified by this search strategy. RESULTS:
      Genome-wide methods have been, or can be, successfully applied on total DNA (DNA
      seq), methylated DNA immunoprecipitation (with tiling array), microRNA (Megaplex)
      and total RNA (RNA-seq). Chromosome- or gene-specific assays have been
      successively applied on placenta RNA (allele ratio) or DNA multiplex ligation
      dependent probe amplification (MLPA). These methods are reviewed for their merits
      and pitfalls with consideration of the placental biology. For the purpose of
      clarity, the technical and clinical characteristics are limited to non-invasive
      prenatal detection of chromosomal aneuploidies, with emphasis on trisomy 21.
      CONCLUSIONS: The technical advances for non-invasive aneuploidy tests based on
      cff DNA and placental mRNA in maternal plasma have been enormous. Multimarker
      assays including genome-wide approaches with the option of qualitative
      information on variation (polymorphism or mutation) besides quantitative
      information are the preferred methods of choice. The time for population-based,
      double blind, large-scale clinical cohort trials has come.

PMID- 21076138
TI  - Deletion of a Ure2 C-terminal prion-inhibiting region promotes the rate of fibril
      seed formation and alters interaction with Hsp40.
AB  - Prions are proteins that can undergo a heritable conformational change to an
      aggregated amyloid-like state, which is then transmitted to other similar
      molecules. Ure2, the nitrogen metabolism regulation factor of Saccharomyces
      cerevisiae, shows prion properties in vivo and forms amyloid fibrils in vitro.
      Ure2 consists of an N-terminal prion-inducing domain and a C-terminal functional
      domain. Previous studies have shown that mutations affecting the prion properties
      of Ure2 are not restricted to the N-terminal prion domain: the deletion of
      residues 151-158 in the C-domain increases the in vivo prion-inducing propensity
      of Ure2. Here, we characterized this mutant in vitro and found that the 151-158
      deletion has minimal effect on the thermodynamic stability or folding properties
      of the protein. However, deletion of residues 151-158 accelerates the nucleation,
      growth and fragmentation of amyloid-like aggregates in vitro, and the aggregates
      formed are able to seed formation of fibrils of the wild-type protein. In
      addition, the absence of 151-158 was found to disrupt the inhibitory effect of
      the Hsp40 chaperone Ydj1 on Ure2 fibril formation. These results suggest that the
      enhanced in vivo prion-inducing ability of the 151-158 deletion mutant is due to
      its enhanced ability to generate prion seeds.

PMID- 21076139
TI  - Screening methods for Chlamydia trachomatis and Neisseria gonorrhoeae infections
      in sexually transmitted infection clinics: what do patients prefer?
AB  - OBJECTIVES: To meet the need for services at sexually transmitted infection (STI)
      clinics, self-obtained vaginal (SOV) swabs or first-catch urine (FCU) samples
      collected at a clinic visit have been proposed as an alternative approach for
      Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) screening. The purpose
      of this clinic-based survey was to determine if non-invasive clinic-based SOV
      swabs and FCU samples for CT and GC screening are acceptable replacements for a
      traditional provider visit. METHODS: Patients seen at STI clinics in three US
      cities completed a self-administered survey of preferences for methods of CT and
      GC screening under hypothetical circumstances. RESULTS: A total of 2887
      participants completed a self-administered questionnaire that contained multiple
      choice questions about their preference. If there was a hypothetical long clinic
      wait, 58% of the survey participants preferred to wait to see a doctor. If the
      clinic had to turn patients away, 41% of patients preferred to come back the next
      business day and 46% preferred to self-collect a sample. The percentages were
      similar across site, demographic and clinical groups. CONCLUSIONS: Clinic-based
      self-collected specimens for CT and GC screening were not preferred by most
      patients who participated in this survey. The findings indicate that more
      detailed information about self-collection practices must be provided for
      patients to adopt this new approach.

PMID- 21076140
TI  - Seroadaptive behaviours among men who have sex with men in San Francisco: the
      situation in 2008.
AB  - OBJECTIVES: To assess changes in seroadaptive behaviours among men who have sex
      with men (MSM) in San Francisco over the past 4 years. METHODS: 461 MSM were
      recruited in 2008 as the second wave of the US National HIV Behavioural
      Surveillance (NHBS) survey in San Francisco. Participants were classified into
      patterns of seroadaptive behaviours based on reported sexual practices (ie,
      episodes of insertive and receptive anal sex), condom use, HIV serostatus and
      partners' serostatus for up to five partners in the preceding 6 months. The
      prevalence of seroadaptive behaviours was compared with the first wave of NHBS,
      which used identical methods in 2004. RESULTS: In 2008, 33.7% of HIV-negative and
      18.9% of HIV-positive MSM used condoms 100% of the time; nearly half (48.0%) of
      HIV-negative MSM and two-thirds (66.7%) of HIV-positive MSM had unprotected anal
      intercourse (UAI). Collectively, seroadaptive behaviours comprised the most
      common form of risk management; 40.5% of HIV-negative MSM and 51.1% of HIV
      positive MSM engaged in some form of seroadaptation, the most common being 'pure
      serosorting' (all UAI with same serostatus partners) reported by 27.5% of HIV
      negative MSM and 22.2% of HIV-positive MSM. None of these behaviours were
      significantly different from their corresponding measures in 2004. CONCLUSIONS:
      Seroadaptation continues to describe the prevailing form of sexual risk
      management for MSM in San Francisco, suggesting that these behaviours are not
      novel and require careful measurement to gauge the true potential for the spread
      of HIV, and nuanced prevention messages to reduce risk.

PMID- 21076141
TI  - EURADOS intercomparison on measurements and Monte Carlo modelling for the
      assessment of americium in a USTUR leg phantom.
AB  - A collaboration of the EURADOS working group on 'Internal Dosimetry' and the
      United States Transuranium and Uranium Registries (USTUR) has taken place to
      carry out an intercomparison on measurements and Monte Carlo modelling
      determining americium deposited in the bone of a USTUR leg phantom. Preliminary
      results and conclusions of this intercomparison exercise are presented here.

PMID- 21076142
TI  - A high-sensitivity multidetector whole-body counter.
AB  - A prototype multidetector shadow-shield whole-body counter is presented to be
      used as a monitor of internal contamination and as a tool in clinical research.
      The counter is equipped with 16 NaI(Tl) detectors located in the central region
      of a shielded tunnel surrounding the subject to be measured. The accuracy of the
      counting efficacy predictions was tested in a group of adults with various body
      shapes and sizes using X-ray absorptiometry. The precision of the total body
      potassium measurements allows the use of the counter in clinical follow-up
      studies.

PMID- 21076143
TI  - Association of population and primary healthcare factors with hospital admission
      rates for chronic obstructive pulmonary disease in England: national cross
      sectional study.
AB  - BACKGROUND: Hospital admission rates for chronic obstructive pulmonary disease
      (COPD) are known to be strongly associated with population factors. Primary care
      services may also affect admission rates, but there is little direct supporting
      evidence. OBJECTIVES: To determine associations between population
      characteristics, diagnosed and undiagnosed COPD prevalence, primary healthcare
      factors, and COPD admission rates primary care trust (PCT) and general practice
      levels in England. DESIGN, SETTING, AND PARTICIPANTS: National cross-sectional
      study (53,676,051 patients in 8,064 practices in 152 English PCTs), combining
      data on hospital admissions, populations, primary healthcare staffing, clinical
      practice quality and access, and prevalence. Main outcome measures Directly and
      indirectly standardised hospital admission rates for COPD, for PCT and practice
      populations. RESULTS: Mean annual COPD admission rates per 100,000 population
      varied from 124.7 to 646.5 for PCTs and 0.0 to 2175.2 for practices. Admissions
      were strongly associated with population deprivation at both levels. In a
      practice-level multivariate Poisson regression, registered and undiagnosed COPD
      prevalence, smoking prevalence and deprivation were risk factors for admission (p
      < 0.001), while healthcare factors- influenza immunisation, patient-reported
      access to consultations within two days, and primary care staffing, were
      protective (p < 0.05). CONCLUSION: Associations of COPD admission rates with
      deprivation, primary healthcare access and supply highlight the need for adequate
      services in deprived areas. An association between admission rates and
      undiagnosed COPD prevalence suggests that case-finding strategies should be
      evaluated. Of the COPD clinical quality indicators, only influenza immunisation
      was associated with reduced admission rates. Patients' experience of access to
      primary care may also be clinically important.

PMID- 21076144
TI  - Echocardiography, troponins and lower extremity ultrasound: the 'Three
      Musketeers' lead the prognosis of acute pulmonary embolism.

PMID- 21076145
TI  - Complete pacemaker lead fracture potentially due to intra-cardiac mass.
AB  - Seven years after the implantation of a dual-chamber pacemaker, a 74-year-old
      woman was referred for syncope. Chest X-ray revealed that the ventricular lead
      was completely broken near the tricuspid valve. Fluoroscopy and transthoracic
      echocardiography found a calcified mass, moving with the proximal part of the
      ventricular lead. Anatomopathology of the atrial tumour remained unknown. Surgery
      was considered too invasive a technique to be performed in our patient, who was
      suffering from dementia.

PMID- 21076146
TI  - Cardiac resynchronization therapy improves exercise heart rate recovery in
      patients with heart failure.
AB  - AIMS: Heart rate (HR) recovery (HRR), defined as the rate of decline in the HR
      immediately following the cessation of exercise, is influenced by autonomic
      function. Heart rate recovery in heart failure (HF) has been shown to correlate
      with severity of HF. Cardiac resynchronization therapy (CRT) improves cardiac
      autonomic functions in HF. We aimed to evaluate the effects of CRT on cardiac
      autonomic function assessed by HRR. METHODS AND RESULTS: Forty-eight patients
      [62.3 +/- 10.7 years; 37 men; left ventricular (LV) ejection fraction 24.8 +/-
      4.1%] with HF were enrolled. A treadmill exercise testing was conducted in all
      patients by using a modified Naughton protocol before and 6 months after CRT.
      Heart rate recovery indices were calculated by subtracting first, second, and
      third minute HR from the maximal HR and designated as HRR1, HRR2, and HRR3,
      respectively. Standard echocardiography was performed before and 6 months after
      CRT. Left ventricular reverse remodelling (LVRM) was quantified as the percentage
      of decline in the LV end-systolic volume after CRT. Mean HRR1 (13.0 +/- 5.9 vs.
      17.9 +/- 8.9 b.p.m., P = 0.001), HRR2 (20.5 +/- 9.3 vs. 23.8 +/- 11.3 b.p.m., P =
      0.001), and HRR3 (25.7 +/- 11.1 vs. 29.2 +/- 12.0 b.p.m., P = 0.001) values
      improved 6 months after CRT. Pearson's analyses revealed a good positive
      correlation between LVRM and DeltaHRR1 (r = 0.642, P = 0.001) and a moderate
      correlation between reduction LVRM and DeltaHRR2 (r = 0.591, P = 0.033) and
      DeltaHRR3 (r = 0.436, P = 0.001). CONCLUSION: Cardiac resynchronization therapy
      favourably alters the cardiac autonomic functions. Heart rate recovery indices
      improved after CRT and the degree of improvement in HRR indices correlated with
      LVRM.

PMID- 21076147
TI  - Association between angiotensin-converting enzyme insertion/deletion gene
      polymorphism and atrial fibrillation: a meta-analysis.
AB  - AIMS: Recent observations have raised concerns regarding the activation of the
      renin-angiotensin system and the development of atrial fibrillation (AF). Some
      initial studies indicated an association between an angiotensin-converting enzyme
      insertion/deletion (ACE I/D) polymorphism and AF, however, the results have been
      inconsistent. Our aim was to perform a meta-analysis of relevant studies to
      assess the validity of this association. METHODS AND RESULTS: PubMed, Cochrane
      clinical trials database, and EMBASE were searched through July 2009, and a
      manual search was also performed. Of the 68 initially identified studies, 18 case
      control studies with 7577 patients were finally analysed. No statistically
      significant associations were found between the ACE I/D polymorphism and AF risk
      in the genetic additive model and dominant model, whereas a significant
      association was observed in the recessive model. A significant heterogeneity
      between individual studies was evident in all three models. Subgroup analyses
      showed a strong association between the ACE I/D polymorphism and hypertensive AF
      without significant heterogeneity. CONCLUSION: Our meta-analysis suggests that
      there is insufficient evidence to demonstrate an association between ACE I/D
      polymorphism and AF risk. However, there seems to be a significant association
      between ACE I/D gene polymorphic variation and AF in patients with hypertension.
      Additional studies are warranted to further explore this association in
      ethnically diverse populations and varied cardiovascular substrates.

PMID- 21076148
TI  - PLEXY: efficient target prediction for box C/D snoRNAs.
AB  - MOTIVATION: Small nucleolar RNAs (snoRNAs) are an abundant class of non-coding
      RNAs with a wide variety of cellular functions including chemical modification of
      RNA, telomere maintanance, pre-rRNA processing and regulatory activities in
      alternative splicing. The main role of box C/D snoRNAs is to determine the
      targets for 2'-O-ribose methylation, which is important for rRNA maturation and
      splicing regulation of some mRNAs. The targets are still unknown, however, for
      many 'orphan' snoRNAs. While a fast and efficient target predictor for box H/ACA
      snoRNAs is available, no comparable tool exists for box C/D snoRNAs, even though
      they bind to their targets in a much less complex manner. RESULTS: PLEXY is a
      dynamic programming algorithm that computes thermodynamically optimal
      interactions of a box C/D snoRNA with a putative target RNA. Implemented as
      scanner for large input sequences and equipped with filters on the duplex
      structure, PLEXY is an efficient and reliable tool for the prediction of box C/D
      snoRNA target sites. AVAILABILITY: The perl script PLEXY is freely available at
      http://www.bioinf.uni-leipzig.de/Software/PLEXY.

PMID- 21076149
TI  - Statistical confidence measures for genome maps: application to the validation of
      genome assemblies.
AB  - MOTIVATION: Genome maps are imperative to address the genetic basis of the
      biology of an organism. While a growing number of genomes are being sequenced
      providing the ultimate genome maps-this being done at an even faster pace now
      using new generation sequencers-the process of constructing intermediate maps to
      build and validate a genome assembly remains an important component for producing
      complete genome sequences. However, current mapping approach lack statistical
      confidence measures necessary to identify precisely relevant inconsistencies
      between a genome map and an assembly. RESULTS: We propose new methods to derive
      statistical measures of confidence on genome maps using a comparative model for
      radiation hybrid data. We describe algorithms allowing to (i) sample from a
      distribution of maps and (ii) exploit this distribution to construct robust maps.
      We provide an example of application of these methods on a dog dataset that
      demonstrates the interest of our approach. AVAILABILITY: Methods are implemented
      in two freely available softwares: Carthagene
      (http://www.inra.fr/mia/T/CarthaGene/) and a companion software (metamap,
      available at: http://snp.toulouse.inra.fr/~servin/index.cgi/Metamap).

PMID- 21076150
TI  - Automated construction and testing of multi-locus gene-gene associations.
AB  - It has been argued that the missing heritability in common diseases may be in
      part due to rare variants and gene-gene effects. Haplotype analyses provide more
      power for rare variants and joint analyses across genes can address multi-gene
      effects. Currently, methods are lacking to perform joint multi-locus association
      analyses across more than one gene/region. Here, we present a haplotype-mining
      gene-gene analysis method, which considers multi-locus data for two genes/regions
      simultaneously. This approach extends our single region haplotype-mining
      algorithm, hapConstructor, to two genes/regions. It allows construction of multi
      locus SNP sets at both genes and tests joint gene-gene effects and interactions
      between single variants or haplotype combinations. A Monte Carlo framework is
      used to provide statistical significance assessment of the joint and interaction
      statistics, thus the method can also be used with related individuals. This tool
      provides a flexible data-mining approach to identifying gene-gene effects that
      otherwise is currently unavailable. AVAILABILITY:
      http://bioinformatics.med.utah.edu/Genie/hapConstructor.html.

PMID- 21076151
TI  - The highly conserved eukaryotic DRG factors are required for efficient
      translation in a manner redundant with the putative RNA helicase Slh1.
AB  - Eukaryotic and archaeal DRG factors are highly conserved proteins with
      characteristic GTPase motifs. This suggests their implication in a central
      biological process, which has so far escaped detection. We show here that the two
      Saccharomyces cerevisiae DRGs form distinct complexes, RBG1 and RBG2, and that
      the former co-fractionate with translating ribosomes. A genetic screen for triple
      synthetic interaction demonstrates that yeast DRGs have redundant function with
      Slh1, a putative RNA helicase also associating with translating ribosomes.
      Translation and cell growth are severely impaired in a triple mutant lacking both
      yeast DRGs and Slh1, but not in double mutants. This new genetic assay allowed us
      to characterize the roles of conserved motifs present in these proteins for
      efficient translation and/or association with ribosomes. Altogether, our results
      demonstrate for the first time a direct role of the highly conserved DRG factors
      in translation and indicate that this function is redundantly shared by three
      factors. Furthermore, our data suggest that important cellular processes are
      highly buffered against external perturbation and, consequently, that redundantly
      acting factors may escape detection in current high-throughput binary genetic
      interaction screens.

PMID- 21076152
TI  - The RIKEN integrated database of mammals.
AB  - The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the
      official undertaking to integrate its mammalian databases produced from multiple
      large-scale programs that have been promoted by the institute. The database
      integrates not only RIKEN's original databases, such as FANTOM, the ENU
      mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and
      the Bioresource Database, but also imported data from public databases, such as
      Ensembl, MGI and biomedical ontologies. Our integrated database has been
      implemented on the infrastructure of publication medium for databases, termed
      SciNetS/SciNeS, or the Scientists' Networking System, where the data and metadata
      are structured as a semantic web and are downloadable in various standardized
      formats. The top-level ontology-based implementation of mammal-related data
      directly integrates the representative knowledge and individual data records in
      existing databases to ensure advanced cross-database searches and reduced
      unevenness of the data management operations. Through the development of this
      database, we propose a novel methodology for the development of standardized
      comprehensive management of heterogeneous data sets in multiple databases to
      improve the sustainability, accessibility, utility and publicity of the data of
      biomedical information.

PMID- 21076153
TI  - Gramene database in 2010: updates and extensions.
AB  - Now in its 10th year, the Gramene database (http://www.gramene.org) has grown
      from its primary focus on rice, the first fully-sequenced grass genome, to become
      a resource for major model and crop plants including Arabidopsis, Brachypodium,
      maize, sorghum, poplar and grape in addition to several species of rice. Gramene
      began with the addition of an Ensembl genome browser and has expanded in the last
      decade to become a robust resource for plant genomics hosting a wide array of
      data sets including quantitative trait loci (QTL), metabolic pathways, genetic
      diversity, genes, proteins, germplasm, literature, ontologies and a fully
      structured markers and sequences database integrated with genome browsers and
      maps from various published studies (genetic, physical, bin, etc.). In addition,
      Gramene now hosts a variety of web services including a Distributed Annotation
      Server (DAS), BLAST and a public MySQL database. Twice a year, Gramene releases a
      major build of the database and makes interim releases to correct errors or to
      make important updates to software and/or data.

PMID- 21076154
TI  - Importance of the proline-rich multimerization domain on the oligomerization and
      nucleic acid binding properties of HIV-1 Vif.
AB  - The HIV-1 viral infectivity factor (Vif) is required for productive infection of
      non-permissive cells, including most natural HIV-1 targets, where it counteracts
      the antiviral activities of the cellular cytosine deaminases APOBEC-3G (A3G) and
      A3F. Vif is a multimeric protein and the conserved proline-rich domain
      (161)PPLP(164) regulating Vif oligomerization is crucial for its function and
      viral infectivity. Here, we expressed and purified wild-type Vif and a mutant
      protein in which alanines were substituted for the proline residues of the
      (161)PPLP(164) domain. Using dynamic light scattering, circular dichroism and
      fluorescence spectroscopy, we established the impact of these mutations on Vif
      oligomerization, secondary structure content and nucleic acids binding
      properties. In vitro, wild-type Vif formed oligomers of five to nine proteins,
      while Vif AALA formed dimers and/or trimers. Up to 40% of the unbound wild-type
      Vif protein appeared to be unfolded, but binding to the HIV-1 TAR apical loop
      promoted formation of beta-sheets. Interestingly, alanine substitutions did not
      significantly affect the secondary structure of Vif, but they diminished its
      binding affinity and specificity for nucleic acids. Dynamic light scattering
      showed that Vif oligomerization, and interaction with folding-promoting nucleic
      acids, favor formation of high molecular mass complexes. These properties could
      be important for Vif functions involving RNAs.

PMID- 21076155
TI  - NLP is a novel transcription regulator involved in VSG expression site control in
      Trypanosoma brucei.
AB  - Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant
      surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream.
      The active VSG is transcribed by RNA polymerase I in one of approximately 15
      telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene
      expression predominantly post-transcriptionally, and how ESs are mono-allelically
      controlled remains a mystery. Here we identify a novel transcription regulator,
      which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is
      key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45-
      to 65-fold derepression of the silent VSG221 ES. NLP is also involved in
      repression of transcription in the inactive VSG Basic Copy arrays,
      minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and
      50-bp simple sequence repeats, the non-transcribed regions around rDNA and
      procyclin, and both active and silent ESs. Blocking NLP synthesis leads to
      downregulation of the active ES, indicating that NLP plays a role in regulating
      appropriate levels of transcription of ESs in both their active and silent state.
      Discovery of the unusual transcription regulator NLP provides new insight into
      the factors that are critical for ES control.

PMID- 21076156
TI  - Targeting atrioventricular differences in ion channel properties for terminating
      acute atrial fibrillation in pigs.
AB  - AIMS: The goal was to terminate atrial fibrillation (AF) by targeting
      atrioventricular differences in ionic properties. METHODS AND RESULTS: Optical
      mapping was used to record electrical activity during carbachol (0.25-0.5 MUM)
      induced AF in pig hearts. The atrial-specific current, I(Kur), was blocked with
      100 MUM 4-aminopyridine (4-AP) or with 0.5 MUM DPO-1. Hearts in AF and
      ventricular fibrillation (VF) were also subjected to increasing levels of
      extracellular K(+) ([K(+)](o): 6-12 mM), compared with controls (4 mM). We
      hypothesized that due to the more negative steady-state half inactivation voltage
      for the atrial Na(+) current, I(Na), compared with the ventricle, AF would
      terminate before VF in hyperkalaemia. Mathematical models were used to interpret
      experimental findings. The I(Kur) block did not terminate AF in a majority of
      experiments (6/9 with 4-AP and 3/4 with DPO-1). AF terminated in mild
      hyperkalaemia ([K(+)](o) <= 10.0 mM; N = 8). In contrast, only two of five VF
      episodes terminated at the maximum ([K(+)](o): 12 mM [K(+)](o)). The I(Kur) block
      did not terminate a simulated rotor in cholinergic AF because its contribution to
      repolarization was dwarfed by the large magnitude of the acetylcholine-activated
      K(+) current (I(K,ACh)). Simulations showed that the lower availability of the
      atrial Na(+) current at depolarized potentials, and a smaller atrial tissue size
      compared with the ventricle, could partly explain the earlier termination of AF
      compared with VF during hyperkalaemia. CONCLUSION: I(Kur) is an ineffective anti
      arrhythmic drug target in cholinergic AF. Manipulating Na(+) current
      'availability' might represent a viable anti-arrhythmic strategy in AF.

PMID- 21076157
TI  - Knowledge of European orthodontic postgraduate students on biostatistics.
AB  - The purpose of this study was to explore the level of knowledge in biostatistics
      of orthodontic postgraduate students. A four-section questionnaire, which
      included a knowledge test/quiz on biostatistics and epidemiology, was developed.
      This questionnaire was distributed to postgraduate programme directors of
      European universities to be delivered to students for completion under mock
      examination conditions (in-class session). The frequency distributions of
      demographic characteristics were examined, the percentages of participants who
      agreed or strongly agreed with each attitudinal statement were calculated, and
      the percentages of participants who felt fairly to highly confident for each
      statement were determined. Knowledge scores were calculated by the percentage of
      correct answers; missing values were counted as incorrect answers. The Student's
      t-test or one-way analysis of variance, where appropriate, was utilized to
      determine the participants' characteristics associated with mean knowledge
      scores. Data were further analysed with multiple linear regression modelling to
      determine the adjusted/unconfounded effect of possible knowledge score
      predictors. A two-tailed P-value of 0.05 was considered statistically significant
      with a 95 percent confidence interval (CI). One hundred and twenty seven from a
      total of 129 orthodontic students who replied completed the questionnaire. The
      mean correct answers of the participants were 43.8 percent with a 95 percent CI
      of 40.2-47.3 percent. This score was not influenced by gender, years elapsed from
      graduation, other advanced degree, or year of study; the sole parameter, which
      seemed to influence this score was attendance at a biostatistics/epidemiology
      course (51.9 versus 39.5 percent score of participants who had previously taken a
      course versus those who had not, P<0.001). A surprising finding was the inability
      of the responders to identify the appropriate use of the chi-square test (11.8
      percent, 95 percent CI: 6.1-17.5 percent). The knowledge on biostatistics of
      orthodontic postgraduate students in Europe is only influenced by previous
      relevant education.

PMID- 21076158
TI  - Antiarrhythmics after ablation of atrial fibrillation (5A Study): six-month
      follow-up study.
AB  - BACKGROUND: We previously demonstrated that treatment with antiarrhythmic drugs
      (AADs) during the first 6 weeks after atrial fibrillation (AF) ablation reduces
      the incidence of clinically significant atrial arrhythmias and need for
      cardioversion or hospitalization for arrhythmia management. Whether early rhythm
      suppression decreases longer-term arrhythmia recurrence is unknown. We now report
      the 6-month follow-up data from this study. METHODS AND RESULTS: The
      Antiarrhythmics After Ablation of Atrial Fibrillation study prospectively
      randomized patients with paroxysmal AF undergoing ablation to either receive (AAD
      group) or not receive (no-AAD group) AAD treatment for the first 6 weeks after
      ablation; all patients received atrioventricular nodal blockers. Physicians were
      encouraged to stop the AADs after the 6-week treatment period. All patients
      underwent 4 weeks of transtelephonic monitoring to document asymptomatic AF and
      an evaluation at 6 weeks and 6 months. A total of 110 patients (71% men) aged
      55+/-9 years were randomized, with 53 to AAD and 57 to no AAD. At 6 months, there
      was no difference in freedom from AF between the early AAD and no-AAD groups
      (38/53 [72%] versus 39/57 [68%]; P=0.84). Lack of early AF recurrence during the
      initial 6-week period was the only independent predictor of 6-month freedom from
      AF (64/76 [84%] without early recurrence versus 13/34 [38%] with early
      recurrence; P=0.0001). CONCLUSIONS: Although short-term use of AADs after AF
      ablation decreases early recurrence of atrial arrhythmias, early use of AADs does
      not prevent arrhythmia recurrence at 6 months. Early AF recurrence on or off AADs
      during the initial 6-week blanking period is a strong independent predictor of
      long-term AF recurrence.

PMID- 21076159
TI  - Association of chronic kidney disease with atrial fibrillation among adults in
      the United States: REasons for Geographic and Racial Differences in Stroke
      (REGARDS) Study.
AB  - BACKGROUND: Atrial fibrillation (AF) is common among patients with end-stage
      renal disease, but few data are available on its prevalence among adults with
      chronic kidney disease (CKD) of lesser severity. methods and results: We
      evaluated the association of CKD with ECG-detected AF among 26 917 participants
      in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a
      population-based cohort of African-American and white US adults >=45 years of
      age. Estimated glomerular filtration rate (eGFR) was calculated using the
      abbreviated Modification of Diet in Renal Disease study equation and albuminuria
      was defined as a urinary albumin to creatinine ratio >=30 mg/g. Participants were
      categorized by renal function: no CKD (eGFR >=60 mL/min/1.73 m(2) without
      albuminuria, n=21 081), stage 1 to 2 CKD (eGFR >=60 mL/min/1.73 m(2) with
      albuminuria n=2938), stage 3 CKD (eGFR 30 to 59 mL/min/1.73 m(2), n=2683) and
      stage 4 to 5 CKD (eGFR <30 mL/min/1.73 m(2), n=215). The prevalence of AF among
      participants without CKD, and with stage 1 to 2, stage 3, and stage 4 to 5 CKD
      was 1.0%, 2.8%, 2.7% and 4.2%, respectively. Compared with participants without
      CKD, the age-, race-, and sex-adjusted odds ratios for prevalent AF were 2.67
      (95% confidence interval, 2.04 to 3.48), 1.68 (95% confidence interval, 1.26 to
      2.24) and 3.52 (95% confidence interval, 1.73 to 7.15) among those with stage 1
      to 2, stage 3, and stage 4 to 5 CKD. The association between CKD and prevalent AF
      remained statistically significant after further multivariable adjustment and was
      consistent across numerous subgroups. CONCLUSIONS: Regardless of severity, CKD is
      associated with an increased prevalence of AF among US adults.

PMID- 21076160
TI  - Incidence, determinants, and prognostic implications of true pleomorphism of
      ventricular tachycardia in patients with implantable cardioverter-defribillators:
      a substudy of the DATAS Trial.
AB  - BACKGROUND: The occurrence of monomorphic ventricular tachycardia (M-VT) with >1
      QRS morphology during the same episode (pleomorphism [PL]) or in different
      episodes (multiple morphologies [MM]) has been described through ECG. Implantable
      cardioverter-defribillator (ICD) electrograms (EGs) provide the opportunity to
      analyze virtually all spontaneous M-VT episodes. We sought to study the
      incidence, determinants, and prognostic significance of PL and MM as assessed by
      ICD-EG in a prospective series of patients with ICDs. METHODS AND RESULTS:
      Spontaneous episodes of M-VT were analyzed before ICD intervention. PL was
      defined as >1 ICD-EG morphology, each having >=6 consecutive identical beats
      during the same VT episode, and MM as >1 ICD-EG morphology in different M-VT
      episodes in the same patient. We analyzed 1881 M-VT episodes from 315 patients
      followed for 17 months. PL and MM occurred in 6% and 19%, respectively, of the
      total population (16% and 62% of patients with M-VT). Recurrent M-VT as diagnosis
      for ICD indication predicted PL and MM. Patients with PL more frequently
      developed MM (85% versus 15%; P<0.001) compared to patients without PL. Total
      mortality (5%) was significantly higher in patients with PL (20%), in patients
      with MM (11.5%), and in women (12%). In multivariate analysis, only PL (odds
      ratio, 5.33; P=0.009) and female sex (odds ratio, 3.1; P=0.038) predicted
      mortality. CONCLUSIONS: In a prospective series of patients with ICDs, mostly
      indicated for secondary prevention, both PL and MM of VT, as judged by ICD-EG,
      were not uncommon and were strongly associated. Female sex and the development of
      PL VT were the only independent predictors of mortality.

PMID- 21076162
TI  - A statute of liberty.

PMID- 21076163
TI  - Theme: non-invasive positive pressure ventilation (NiPPV) in the ED.

PMID- 21076164
TI  - Emergency medicine provider efficiency: the learning curve, equilibration and
      point of diminishing returns.
AB  - OBJECTIVE: This study described the spectrum of emergency department (ED)
      physician performance correlating annual workload, experience and facility
      issues. METHODS: Retrospective review reported physician hours worked comparing
      productivity measures--patients per hour (PPH) or relative value unit (RVU) per
      hour, as 'best fit' trend line and facility volume subgroups by analysis of
      variance. RESULTS: 912 physicians evaluated 2,407,833 patients in 61 ED. Staff
      productivity was 1.72+/-0.44 PPH (1.2+/-0.30-2.1+/-0.32 PPH) and 4.43+/-1.21
      RVU/h (2.9+/-0.80-5.4+/-0.82 RVU/h). There was less variation with facility size
      2.58+/-0.36 (2.41+/-0.22-2.72+/-0.37 RVU/visit) from smaller to larger (p<0.001).
      Maximal efficiency occurs at 5.0 RVU/h generated at 1550 annual hours (130
      monthly) compared with 1800 h full-time equivalent (FTE) physicians (R(2)=0.084).
      Productivity begins at 4.0 RVU/h for casual (<250 h/year), 4.4 RVU/h for part
      time (<500 h), achieving equilibrium (5.0 RVU/h) for three-quarters to full time
      (1250-1800 h) with a decline in full-time providers (2000-2500 h/year).
      Efficiency was less in smaller ED less than 15,000 (1.22+/-0.30 PPH, 2.95+/-0.80
      RVU/h) compared with larger greater than 45,000 (2.07+/-0.32 PPH, 5.43+/-0.82
      RVU/h; p<0.001). The RVU/visit generated were less varied (2.41+/-0.22) in
      smaller versus (2.64+/-0.38) larger facilities with a 2.8 RVU/h equilibration
      point (p<0.001). CONCLUSION: Maximal productivity is reached at 86% (1550 h)
      annual workload and efficiency declines at conventional FTE (~ 1800 h). A
      distinct 'learning curve' was found in newer, casual providers and smaller
      facilities.

PMID- 21076165
TI  - Does the pandemic medical early warning score system correlate with disposition
      decisions made at patient contact by emergency care practitioners?
AB  - OBJECTIVE: To assess the performance of the pandemic medical early warning score
      (PMEWS) in a cohort of adult patients seen in the community by emergency care
      practitioners (ECP) and its correlation with ECP decision-making to either 'treat
      and leave' or transfer for hospital assessment. METHODS: Cases attended by ECP in
      South Yorkshire in 2007 in which the final ECP working diagnosis was a
      respiratory condition were retrospectively identified from the Yorkshire
      Ambulance Service database. The patient report forms were reviewed for the PMEWS
      variables and scores calculated using the PMEWS system. The outcome measure was
      management in the community versus transport to hospital. Receiver operating
      characteristics (ROC) curves were calculated to assess the discrimination of
      PMEWS. RESULTS: A cohort of 300 patients was assessed. 217 (72%) were aged 65
      years or over, and 272 (91%) had either comorbid disease or impaired functional
      status. 98 (33%) were deemed to need hospital assessment or admission. The ROC
      curves suggested that there is good correlation between the PMEWS score and the
      decision to discharge. CONCLUSIONS: PMEWS correlates well with decisions to admit
      to hospital or leave at home made by extended role practitioners in the patient
      group studied; however, further prospective work is required to further validate
      early warning scoring systems in prehospital care.

PMID- 21076161
TI  - A common connexin-40 gene promoter variant affects connexin-40 expression in
      human atria and is associated with atrial fibrillation.
AB  - BACKGROUND: A common single-nucleotide polymorphism (SNP) in the promoter of the
      Connexin-40 (Cx40) gene GJA5 was suggested to affect Cx40 promoter activity and
      the risk of atrial fibrillation (AF), but the role of other common Cx40
      polymorphisms is unknown. METHODS AND RESULTS: Eight SNPs within the Cx40 gene
      region were tested for association with Cx40 levels measured in atrial tissue
      from 61 individuals. The previously described Cx40 promoter SNP (rs35594137, -44G
      >A) was not associated with Cx40 mRNA levels. However, a common SNP (rs10465885)
      located in the TATA box of an alternative Cx40 promoter was strongly associated
      with Cx40 mRNA expression (P<0.0001) and displayed strong and consistent allelic
      expression imbalance in human atrial tissue. A promoter-luciferase assay in
      cultured murine cardiomyocytes demonstrated reduced activity of the promoter
      containing the minor allele of this SNP (P<0.0001). Both rs35594137 and
      rs10465885 were tested for association with early-onset lone AF (<=60 years of
      age) in 384 cases and 3010 population control subjects. rs10465885 was associated
      with the AF phenotype (odds ratio, 1.18; P=0.046). This result was confirmed in a
      meta-analysis including 2 additional early-onset lone AF case-control cohorts
      (odds ratio, 1.16, P=0.022). rs35594137 was not associated with the lone AF
      phenotype in any of the cohorts studied or in a combined analysis. CONCLUSIONS: A
      previously described Cx40 promoter SNP was not found to influence Cx40 expression
      or risk of AF. We describe an alternate promoter polymorphism that directly
      affects levels of Cx40 mRNA in vivo and is associated with early-onset lone AF.

PMID- 21076166
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1. Optimal body position in oral poisoning cases.

PMID- 21076168
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3. Binaxnow malaria rapid diagnostic test in returning travellers.

PMID- 21076169
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2. Pelvic splints for all types of suspected pelvic fractures.

PMID- 21076170
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4. Positioning of compartment pressure monitors in lower limb
      fractures.

PMID- 21076171
TI  - Intraosseus access simulation: the Crunchie solution.

PMID- 21076173
TI  - Occupational exposure limits--at the crossroads.

PMID- 21076175
TI  - Creating clinical practice guidelines for the cardiology 'world'.

PMID- 21076174
TI  - Association between familial atrial fibrillation and risk of new-onset atrial
      fibrillation.
AB  - CONTEXT: Although the heritability of atrial fibrillation (AF) is established,
      the contribution of familial AF to predicting new-onset AF remains unknown.
      OBJECTIVE: To determine whether familial occurrence of AF is associated with new
      onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS: The
      Framingham Heart Study, a prospective community-based cohort study started in
      1948. Original and Offspring Cohort participants were aged at least 30 years,
      were free of AF at the baseline examination, and had at least 1 parent or sibling
      enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD,
      13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME
      MEASURES: Incremental predictive value of incorporating different features of
      familial AF (any familial AF, premature familial AF [onset <=65 years old],
      number of affected relatives, and youngest age of onset in a relative) into a
      risk model for new-onset AF. RESULTS: Across 11,971 examinations during the
      period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185
      participants (26.8%) and premature familial AF occurred among 351 participants
      (7.9%). Atrial fibrillation occurred more frequently among participants with
      familial AF than without familial AF (unadjusted absolute event rates of 5.8% and
      3.1%, respectively). The association was not attenuated by adjustment for AF risk
      factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI],
      1.13-1.74) or reported AF-related genetic variants. Among the different features
      of familial AF examined, premature familial AF was associated with improved
      discrimination beyond traditional risk factors to the greatest extent
      (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature
      familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes
      in integrated discrimination improvement were observed with premature familial AF
      (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds
      of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF
      (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless
      net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P
      = .009). CONCLUSIONS: In this cohort, familial AF was associated with an
      increased risk of AF that was not attenuated by adjustment for AF risk factors
      including genetic variants. Assessment of premature familial AF was associated
      with a very slight increase in predictive accuracy compared with traditional risk
      factors.

PMID- 21076176
TI  - Proteomic analysis of fatty-acylated proteins in mammalian cells with chemical
      reporters reveals S-acylation of histone H3 variants.
AB  - Bioorthogonal chemical reporters are useful tools for visualizing and identifying
      post-translational modifications on proteins. Here we report the proteomic
      analysis of mammalian proteins targeted by a series of fatty acid chemical
      reporters ranging from myristic to stearic acid. The large-scale analysis of
      total cell lysates from fully solubilized Jurkat T cells identified known fatty
      acylated proteins and many new candidates, including nuclear proteins and in
      particular histone H3 variants. We demonstrate that histones H3.1, H3.2, and H3.3
      are modified with fatty acid chemical reporters and identify the conserved
      cysteine 110 as a new site of S-acylation on histone H3.2. This newly discovered
      modification of histone H3 could have implications for nuclear organization and
      chromatin regulation. The unbiased proteomic analysis of fatty-acylated proteins
      using chemical reporters has revealed a greater diversity of lipid-modified
      proteins in mammalian cells and identified a novel post-translational
      modification of histones.

PMID- 21076177
TI  - Core transcription factors, Oct4, Sox2 and Nanog, individually form complexes
      with nucleophosmin (Npm1) to control embryonic stem (ES) cell fate determination.
AB  - Embryonic stem (ES) cells have therapeutic potential in regenerative medicine,
      although the molecular mechanism controlling their pluripotency is not completely
      understood. Depending on interaction partners most proteins can be involved in
      several different cellular mechanisms. We screened for novel protein-protein
      interactions using in situ proximity ligation assays together with specific
      antibodies directed against known important ES cell proteins. We found that all
      three core transcription factors, namely Oct4, Sox2 and Nanog, individually
      formed complexes with nucleophosmin (Npm1). We showed that the Npm1/Sox2 complex
      was sustained when cells were induced to differentiate by retinoic acid, while
      decreased in the other differentiation pathways. Moreover, Oct4 also formed
      individual complexes with translationally controlled tumor protein (Tpt1).
      Downregulation of Npm1 or Tpt1 increased mRNA levels for genes involved in
      mesoderm and ectoderm differentiation pathways, respectively, indicative of their
      involvement in ES cell maintenance. We have here described four novel protein
      protein interactions in ES cell involving all three core transcription factors.
      Our findings improve the current knowledge about ES cell-specific protein
      networks and indicate the importance of Npm1 and Tpt1 to maintain the ES cell
      phenotype.

PMID- 21076178
TI  - Growth signaling promotes chronological aging in budding yeast by inducing
      superoxide anions that inhibit quiescence.
AB  - Inhibition of growth signaling pathways protects against aging and age-related
      diseases in parallel with reduced oxidative stress. The relationships between
      growth signaling, oxidative stress and aging remain unclear. Here we report that
      in Saccharomyces cerevisiae, alterations in growth signaling pathways impact
      levels of superoxide anions that promote chronological aging and inhibit growth
      arrest of stationary phase cells in G0/G1. Factors that decrease intracellular
      superoxide anions in parallel with enhanced longevity and more efficient G0/G1
      arrest include genetic inactivation of growth signaling pathways that inhibit
      Rim15p, which activates oxidative stress responses, and downregulation of these
      pathways by caloric restriction. Caloric restriction also reduces superoxide
      anions independently of Rim15p by elevating levels of H2O2, which activates
      superoxide dismutases. In contrast, high glucose or mutations that activate
      growth signaling accelerate chronological aging in parallel with increased
      superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High
      glucose also activates DNA damage responses and preferentially kills stationary
      phase cells that fail to arrest growth in G0/G1. These findings suggest that
      growth signaling promotes chronological aging in budding yeast by elevating
      superoxide anions that inhibit quiescence and induce DNA replication stress. A
      similar mechanism likely contributes to aging and age-related diseases in complex
      eukaryotes.

PMID- 21076179
TI  - HDAC pharmacological inhibition promotes cell death through the eIF2alpha kinases
      PKR and GCN2.
AB  - Histone deacetylase inhibitors (HDACi) comprise a family of chemotherapeutic
      agents used in the clinic to treat cutaneous T-cell lymphoma and tested for the
      therapy of other malignancies. Previous reports have shown that eIF2alpha
      phosphorylation is induced upon treatment with HDACi. However the kinase
      responsible for this phosphorylation or the biological significance of this
      finding is not yet established. Herein, we show that eIF2alpha phosphorylation is
      not attributed to a specific eIF2alpha kinase, but rather different eIF2alpha
      kinases contribute to its upregulation in response to the HDACi, vorinostat. More
      importantly our data indicate that eIF2alpha phosphorylation acts in a
      cytoprotective manner, whereas the eIF2alpha kinases PKR and GCN2 promote
      vorinostat-induced apoptosis. These results reveal a dual nature for eIF2alpha
      kinases with potential implications in the treatment with histone deacetylase
      inhibitors.

PMID- 21076180
TI  - Linking Klotho, Nrf2, MAP kinases and aging.

PMID- 21076181
TI  - The telomere protein tankyrase 1 regulates DNA damage responses at telomeres.
AB  - The proliferative potential of eukaryotic cells is critically dependent upon the
      maintenance of functional telomeres, the protein-DNA complexes that cap the ends
      of chromosomes. A paper published in this issue of Aging describes that the
      telomere protein tankyrase 1 regulates DNA damage responses at telomeres.

PMID- 21076184
TI  - Functional stability of endothelial cells on a novel hybrid scaffold for vascular
      tissue engineering.
AB  - Porous and pliable conduits made of biodegradable polymeric scaffolds offer great
      potential for the development of blood vessel substitutes but they generally lack
      signals for cell proliferation, survival and maintenance of a normal phenotype.
      In this study we have prepared and evaluated porous poly(epsilon-caprolactone)
      (PCL) integrated with fibrin composite (FC) to get a biomimetic hybrid scaffold
      (FC PCL) with the biological properties of fibrin, fibronectin (FN), gelatin,
      growth factors and glycosaminoglycans. Reduced platelet adhesion on a human
      umbilical vein endothelial cell-seeded hybrid scaffold as compared to bare PCL or
      FC PCL was observed, which suggests the non-thrombogenic nature of the tissue
      engineered scaffold. Analysis of real-time polymerase chain reaction (RT-PCR)
      after 5 days of endothelial cell (EC) culture on a hybrid scaffold indicated that
      the prothrombotic von Willebrand factor and plasminogen activator inhibitor (PAI)
      were quiescent and stable. Meanwhile, dynamic expressions of tissue plasminogen
      activator (tPA) and endothelial nitric oxide synthase indicated the desired cell
      phenotype on the scaffold. On the hybrid scaffold, shear stress could induce
      enhanced nitric oxide release, which implicates vaso-responsiveness of EC grown
      on the tissue-engineered construct. Significant upregulation of mRNA for
      extracellular matrix (ECM) proteins, collagen IV and elastin, in EC was detected
      by RT-PCR after growing them on the hybrid scaffold and FC-coated tissue culture
      polystyrene (FC TCPS) but not on FN-coated TCPS. The results indicate that the FC
      PCL hybrid scaffold can accomplish a remodeled ECM and non-thrombogenic EC
      phenotype, and can be further investigated as a scaffold for cardiovascular
      tissue engineering.

PMID- 21076183
TI  - Is shortening of telomeres the missing link between aging and the Type 2 Diabetes
      epidemic?

PMID- 21076182
TI  - The sweet taste of death: glucose triggers apoptosis during yeast chronological
      aging.
AB  - As time goes by, a postmitotic cell ages following a degeneration process
      ultimately ending in cell death. This phenomenon is evolutionary conserved and
      present in unicellular eukaryotes as well, making the yeast chronological aging
      system an appreciated model. Here, single cells die in a programmed fashion (both
      by apoptosis and necrosis) for the benefit of the whole population. Besides its
      meaning for aging and cell death research, age-induced programmed cell death
      represents the first experimental proof for the so-called group selection theory:
      Apoptotic genes became selected during evolution because of the benefits they
      might render to the whole cell culture and not to the individual cell. Many anti
      aging stimuli have been discovered in the yeast chronological aging system and
      have afterwards been confirmed in higher cells or organisms. New work from the
      Burhans group (this issue) now demonstrates that glucose signaling has a
      progeriatric effect on chronologically aged yeast cells: Glucose administration
      results in a diminished efficacy of cells to enter quiescence, finally causing
      superoxide-mediated replication stress and apoptosis.

PMID- 21076186
TI  - Effects of laminin blended with chitosan on axon guidance on patterned
      substrates.
AB  - Axon guidance is a crucial consideration in the design of tissue scaffolds used
      to promote nerve regeneration. Here we investigate the combined use of laminin (a
      putative axon adhesion and guidance molecule) and chitosan (a leading candidate
      base material for the construction of scaffolds) for promoting axon guidance in
      cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid
      prototyping (DBRP) technique, two-dimensional grid patterns were created by
      dispensing chitosan or laminin-blended chitosan substrate strands oriented in
      orthogonal directions. In vitro experiments illustrated DRG neurites on these
      patterns preferentially grew upon and followed the laminin-blended chitosan
      pathways. These results suggest that an orientation of neurite growth can be
      achieved in an artificially patterned substrate by creating selectively
      biofunctional pathways. The DBRP technique may provide improved strategies for
      the use of biofunctional pathways in the design of three-dimensional scaffolds
      for guidance of nerve repair.

PMID- 21076187
TI  - Hydroxyapatite coatings deposited by liquid precursor plasma spraying: controlled
      dense and porous microstructures and osteoblastic cell responses.
AB  - Hydroxyapatite coatings were deposited on Ti-6Al-4V substrates by a novel plasma
      spraying process, the liquid precursor plasma spraying (LPPS) process. X-ray
      diffraction results showed that the coatings obtained by the LPPS process were
      mainly composed of hydroxyapatite. The LPPS process also showed excellent control
      on the coating microstructure, and both nearly fully dense and highly porous
      hydroxyapatite coatings were obtained by simply adjusting the solid content of
      the hydroxyapatite liquid precursor. Scanning electron microscope observations
      indicated that the porous hydroxyapatite coatings had pore size in the range of
      10-200 um and an average porosity of 48.26 +/- 0.10%. The osteoblastic cell
      responses to the dense and porous hydroxyapatite coatings were evaluated with
      human osteoblastic cell MG-63, in respect of the cell morphology, proliferation
      and differentiation, with the hydroxyapatite coatings deposited by the
      atmospheric plasma spraying (APS) process as control. The cell experiment results
      indicated that the heat-treated LPPS coatings with a porous structure showed the
      best cell proliferation and differentiation among all the hydroxyapatite
      coatings. Our results suggest that the LPPS process is a promising plasma
      spraying technique for fabricating hydroxyapatite coatings with a controllable
      microstructure, which has great potential in bone repair and replacement
      applications.

PMID- 21076185
TI  - Benchtop fabrication of PDMS microstructures by an unconventional
      photolithographic method.
AB  - Poly(dimethylsiloxane) (PDMS) microstructures have been widely used in bio
      microelectromechanical systems (bio-MEMS) for various types of analytical,
      diagnostic and therapeutic applications. However, PDMS-based soft lithographic
      techniques still use conventional microfabrication processes to generate a master
      mold, which requires access to clean room facilities and costly equipment. With
      the increasing use of these systems in various fields, the development of
      benchtop systems for fabricating microdevices is emerging as an important
      challenge in their widespread use. Here we demonstrate a simple, low-cost and
      rapid method to fabricate PDMS microstructures by using micropatterned
      poly(ethylene glycol) diacrylate (PEGDA) master molds. In this method, PEGDA
      microstructures were patterned on a glass substrate by photolithography under
      ambient conditions and by using simple tools. The resulting PEGDA structures were
      subsequently used to generate PDMS microstructures by standard molding in a
      reproducible and repeatable manner. The thickness of the PEGDA microstructures
      was controllable from 15 to 300 um by using commonly available spacer materials.
      We also demonstrate the use of this method to fabricate microfluidic channels
      capable of generating concentration gradients. In addition, we fabricated PEGDA
      microstructures by photolithography from the light generated from commonly
      available laminar cell culture hood. These data suggest that this approach could
      be beneficial for fabricating low-cost PDMS-based microdevices in resource
      limited settings.

PMID- 21076188
TI  - Electron density uncertainties in proton computed tomography.
AB  - An expression is derived for the electron density resolution of proton computed
      tomography obtained from algebraic reconstruction methods. The dependence of the
      resolution on system parameters is clarified and methods for achieving the best
      resolutions possible are suggested. Comparison of our results with previous ones
      from the literature is included as well as a discussion of the limitations of the
      results.

PMID- 21076189
TI  - Predicted risks of second malignant neoplasm incidence and mortality due to
      secondary neutrons in a girl and boy receiving proton craniospinal irradiation.
AB  - The purpose of this study was to compare the predicted risks of second malignant
      neoplasm (SMN) incidence and mortality from secondary neutrons for a 9-year-old
      girl and a 10-year-old boy who received proton craniospinal irradiation (CSI).
      SMN incidence and mortality from neutrons were predicted from equivalent doses to
      radiosensitive organs for cranial, spinal and intracranial boost fields.
      Therapeutic proton absorbed dose and equivalent dose from neutrons were
      calculated using Monte Carlo simulations. Risks of SMN incidence and mortality in
      most organs and tissues were predicted by applying risks models from the National
      Research Council of the National Academies to the equivalent dose from neutrons;
      for non-melanoma skin cancer, risk models from the International Commission on
      Radiological Protection were applied. The lifetime absolute risks of SMN
      incidence due to neutrons were 14.8% and 8.5%, for the girl and boy,
      respectively. The risks of a fatal SMN were 5.3% and 3.4% for the girl and boy,
      respectively. The girl had a greater risk for any SMN except colon and liver
      cancers, indicating that the girl's higher risks were not attributable solely to
      greater susceptibility to breast cancer. Lung cancer predominated the risk of SMN
      mortality for both patients. This study suggests that the risks of SMN incidence
      and mortality from neutrons may be greater for girls than for boys treated with
      proton CSI.

PMID- 21076190
TI  - Dose perturbations and image artifacts caused by carbon-coated ceramic and
      stainless steel fiducials used in proton therapy for prostate cancer.
AB  - Image-guided radiation therapy using implanted fiducial markers is a common
      solution for prostate localization to improve targeting accuracy. However,
      fiducials that are typically used for conventional photon radiotherapy cause
      large dose perturbations in patients who receive proton radiotherapy. A proposed
      solution has been to use fiducials of lower atomic number (Z) materials to
      minimize this effect in tissue, but the effects of these fiducials on dose
      distributions have not been quantified. The objective of this study was to
      analyze the magnitude of the dose perturbations caused by select lower-Z
      fiducials (a carbon-coated zirconium dioxide fiducial and a plastic-coated
      stainless steel fiducial) and compare them to perturbations caused by
      conventional gold fiducials. Sets of phantoms were used to assess select
      components of the effects on dose. First, the fiducials were assessed for
      radiographic visibility using both conventional computed tomography (CT) and an
      on-board kilovoltage imaging device at our proton therapy center. CT streak
      artifacts from the fiducials were also measured in a separate phantom. Second,
      dose perturbations were measured downstream of the fiducials using radiochromic
      film. The magnitude of dose perturbation was characterized as a function of
      marker material, implantation depth and orientation with respect to the beam
      axis. The radiographic visibility of the markers was deemed to be acceptable for
      clinical use. The dose measurements showed that the perpendicularly oriented
      zirconium dioxide and stainless steel fiducials located near the center of
      modulation of the proton beam perturbed the dose by less than 10%, but that the
      same fiducials in a parallel orientation near the end of the range of the beam
      could perturb the dose by as much as 38%. This suggests that carbon-coated and
      stainless steel fiducials could be used in proton therapy if they are located far
      from the end of the range of the beam and if they are oriented perpendicular to
      the beam axis.

PMID- 21076191
TI  - Accuracy of out-of-field dose calculations by a commercial treatment planning
      system.
AB  - The dosimetric accuracy of treatment planning systems (TPSs) decreases for
      locations outside the treatment field borders. However, the true accuracy of
      specific TPSs for locations beyond the treatment field borders is not well
      documented. Our objective was to quantify the accuracy of out-of-field dose
      predicted by the commercially available Eclipse version 8.6 TPS (Varian Medical
      Systems, Palo Alto, CA) for a clinical treatment delivered on a Varian Clinac
      2100. We calculated (in the TPS) and determined (with thermoluminescent
      dosimeters) doses at a total of 238 points of measurement (with distance from the
      field edge ranging from 3.75 to 11.25 cm). Our comparisons determined that the
      Eclipse TPS underestimated out-of-field doses by an average of 40% over the range
      of distances examined. As the distance from the treatment field increased, the
      TPS underestimated the dose with increasing magnitude--up to 55% at 11.25 cm from
      the treatment field border. These data confirm that accuracy beyond the treatment
      border is inadequate, and out-of-field data from TPSs should be used only with a
      clear understanding of this limitation. Studies that require accurate out-of
      field dose should use other dose reconstruction methods, such as direct
      measurements or Monte Carlo calculations.

PMID- 21076192
TI  - A GPU implementation of a track-repeating algorithm for proton radiotherapy dose
      calculations.
AB  - An essential component in proton radiotherapy is the algorithm to calculate the
      radiation dose to be delivered to the patient. The most common dose algorithms
      are fast but they are approximate analytical approaches. However their level of
      accuracy is not always satisfactory, especially for heterogeneous anatomical
      areas, like the thorax. Monte Carlo techniques provide superior accuracy;
      however, they often require large computation resources, which render them
      impractical for routine clinical use. Track-repeating algorithms, for example the
      fast dose calculator, have shown promise for achieving the accuracy of Monte
      Carlo simulations for proton radiotherapy dose calculations in a fraction of the
      computation time. We report on the implementation of the fast dose calculator for
      proton radiotherapy on a card equipped with graphics processor units (GPUs)
      rather than on a central processing unit architecture. This implementation
      reproduces the full Monte Carlo and CPU-based track-repeating dose calculations
      within 2%, while achieving a statistical uncertainty of 2% in less than 1 min
      utilizing one single GPU card, which should allow real-time accurate dose
      calculations.

PMID- 21076193
TI  - Methodology for determining doses to in-field, out-of-field and partially in
      field organs for late effects studies in photon radiotherapy.
AB  - An important but little examined aspect of radiation dosimetry studies involving
      organs outside the treatment field is how to assess dose to organs that are
      partially within a treatment field; this question is particularly important for
      studies intended to measure total absorbed dose in order to predict the risk of
      radiogenic late effects, such as second cancers. The purpose of this
      investigation was therefore to establish a method to categorize organs as in
      field, out-of-field or partially in-field that would be applicable to both
      conventional and modern radiotherapy techniques. In this study, we defined
      guidelines to categorize the organs based on isodose inclusion criteria,
      developed methods to assess doses to partially in-field organs, and then tested
      the methods by applying them to a case of intensity-modulated radiotherapy for
      hepatocellular carcinoma based on actual patient data. For partially in-field
      organs, we recommend performing a sensitivity test to determine whether potential
      inaccuracies in low-dose regions of the DVH (from the treatment planning system)
      have a substantial effect on the mean organ dose, i.e. >5%. In such cases, we
      suggest supplementing calculated DVH data with measured dosimetric data using a
      volume-weighting technique to determine the mean dose.

PMID- 21076194
TI  - Adjustment of the lateral and longitudinal size of scanned proton beam spots
      using a pre-absorber to optimize penumbrae and delivery efficiency.
AB  - In scanned-beam proton therapy, the beam spot properties, such as the lateral and
      longitudinal size and the minimum achievable range, are influenced by beam
      optics, scattering media and drift spaces in the treatment unit. Currently
      available spot scanning systems offer few options for adjusting these properties.
      We investigated a method for adjusting the lateral and longitudinal spot size
      that utilizes downstream plastic pre-absorbers located near a water phantom. The
      spot size adjustment was characterized using Monte Carlo simulations of a
      modified commercial scanned-beam treatment head. Our results revealed that the
      pre-absorbers can be used to reduce the lateral full width at half maximum (FWHM)
      of dose spots in water by up to 14 mm, and to increase the longitudinal extent
      from about 1 mm to 5 mm at residual ranges of 4 cm and less. A large factor in
      manipulating the lateral spot sizes is the drift space between the pre-absorber
      and the water phantom. Increasing the drift space from 0 cm to 15 cm leads to an
      increase in the lateral FWHM from 2.15 cm to 2.87 cm, at a water-equivalent depth
      of 1 cm. These findings suggest that this spot adjustment method may improve the
      quality of spot-scanned proton treatments.

PMID- 21076195
TI  - Effect of organ size and position on out-of-field dose distributions during
      radiation therapy.
AB  - Mantle field irradiation has historically been the standard radiation treatment
      for Hodgkin lymphoma. It involves treating large regions of the chest and neck
      with high doses of radiation (up to 30 Gy). Previous epidemiological studies on
      the incidence of second malignancies following radiation therapy for Hodgkin
      lymphoma have revealed an increased incidence of second tumors in various organs,
      including lung, breast, thyroid and digestive tract. Multiple other studies,
      including the Surveillance, Epidemiology and End Results, indicated an increased
      incidence in digestive tract including stomach cancers following mantle field
      radiotherapy. Assessment of stomach dose is challenging because the stomach is
      outside the treatment field but very near the treatment border where there are
      steep dose gradients. In addition, the stomach can vary greatly in size and
      position. We sought to evaluate the dosimetric impact of the size and variable
      position of the stomach relative to the field border for a typical Hodgkin
      lymphoma mantle field irradiation. The mean stomach dose was measured using
      thermoluminescent dosimetry for nine variations in stomach size and position. The
      mean doses to the nine stomach variations ranged from 0.43 to 0.83 Gy when 30 Gy
      was delivered to the treatment isocenter. Statistical analyses indicated that
      there were no significant differences in the mean stomach dose when the stomach
      was symmetrically expanded up to 3 cm or shifted laterally (medial, anterior or
      posterior shifts) by up to 3 cm. There was, however, a significant (P > 0.01)
      difference in the mean dose when the stomach was shifted superiorly or inferiorly
      by >=2.5 cm.

PMID- 21076196
TI  - Estimate of the uncertainties in the relative risk of secondary malignant
      neoplasms following proton therapy and intensity-modulated photon therapy.
AB  - Theoretical calculations have shown that proton therapy can reduce the incidence
      of radiation-induced secondary malignant neoplasms (SMN) compared with photon
      therapy for patients with prostate cancer. However, the uncertainties associated
      with calculations of SMN risk had not been assessed. The objective of this study
      was to quantify the uncertainties in projected risks of secondary cancer
      following contemporary proton and photon radiotherapies for prostate cancer. We
      performed a rigorous propagation of errors and several sensitivity tests to
      estimate the uncertainty in the ratio of relative risk (RRR) due to the largest
      contributors to the uncertainty: the radiation weighting factor for neutrons, the
      dose-response model for radiation carcinogenesis and interpatient variations in
      absorbed dose. The interval of values for the radiation weighting factor for
      neutrons and the dose-response model were derived from the literature, while
      interpatient variations in absorbed dose were taken from actual patient data. The
      influence of each parameter on a baseline RRR value was quantified. Our analysis
      revealed that the calculated RRR was insensitive to the largest contributors to
      the uncertainty. Uncertainties in the radiation weighting factor for neutrons,
      the shape of the dose-risk model and interpatient variations in therapeutic and
      stray doses introduced a total uncertainty of 33% to the baseline RRR
      calculation.

PMID- 21076197
TI  - An analytic model of neutron ambient dose equivalent and equivalent dose for
      proton radiotherapy.
AB  - Stray neutrons generated in passively scattered proton therapy are of concern
      because they increase the risk that a patient will develop a second cancer.
      Several investigations characterized stray neutrons in proton therapy using
      experimental measurements and Monte Carlo simulations, but capabilities of
      analytical methods to predict neutron exposures are less well developed. The goal
      of this study was to develop a new analytical model to calculate neutron ambient
      dose equivalent in air and equivalent dose in phantom based on Monte Carlo
      modeling of a passively scattered proton therapy unit. The accuracy of the new
      analytical model is superior to a previous analytical model and comparable to the
      accuracy of typical Monte Carlo simulations and measurements. Predictions from
      the new analytical model agreed reasonably well with corresponding values
      predicted by a Monte Carlo code using an anthropomorphic phantom.

PMID- 21076198
TI  - Assessment of targeting accuracy of a low-energy stereotactic radiosurgery
      treatment for age-related macular degeneration.
AB  - Age-related macular degeneration (AMD), a leading cause of blindness in the
      United States, is a neovascular disease that may be controlled with radiation
      therapy. Early patient outcomes of external beam radiotherapy, however, have been
      mixed. Recently, a novel multimodality treatment was developed, comprising
      external beam radiotherapy and concomitant treatment with a vascular endothelial
      growth factor inhibitor. The radiotherapy arm is performed by stereotactic
      radiosurgery, delivering a 16 Gy dose in the macula (clinical target volume, CTV)
      using three external low-energy x-ray fields while adequately sparing normal
      tissues. The purpose of our study was to test the sensitivity of the delivery of
      the prescribed dose in the CTV using this technique and of the adequate sparing
      of normal tissues to all plausible variations in the position and gaze angle of
      the eye. Using Monte Carlo simulations of a 16 Gy treatment, we varied the gaze
      angle by +/-5 degrees  in the polar and azimuthal directions, the linear
      displacement of the eye +/-1 mm in all orthogonal directions, and observed the
      union of the three fields on the posterior wall of spheres concentric with the
      eye that had diameters between 20 and 28 mm. In all cases, the dose in the CTV
      fluctuated <6%, the maximum dose in the sclera was <20 Gy, the dose in the optic
      disc, optic nerve, lens and cornea were <0.7 Gy and the three-field junction was
      adequately preserved. The results of this study provide strong evidence that for
      plausible variations in the position of the eye during treatment, either by the
      setup error or intrafraction motion, the prescribed dose will be delivered to the
      CTV and the dose in structures at risk will be kept far below tolerance doses.

PMID- 21076199
TI  - Risk of second malignant neoplasm following proton versus intensity-modulated
      photon radiotherapies for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), the sixth most common cancer in the world, is a
      global health concern. Radiotherapy for HCC is uncommon, largely because of the
      likelihood of radiation-induced liver disease, an acute side effect that is often
      fatal. Proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT)
      may offer HCC patients a better option for treating the diseased liver tissue
      while largely sparing the surrounding tissues, especially the non-tumor liver.
      However, even advanced radiotherapies carry a risk of late effects, including
      second malignant neoplasms (SMNs). It is unclear whether PBT or IMRT confers less
      risk of an SMN than the other. The purpose of this study was to compare the
      predicted risk of developing an SMN for a patient with HCC between PBT and IMRT.
      For both treatments, radiation doses in organs and tissues from primary radiation
      were determined using a treatment planning system; doses in organs and tissues
      from stray radiation from PBT were determined using Monte Carlo simulations and
      from IMRT using thermo-luminescent dosimeter measurements. Risk models of SMN
      incidence were taken from the literature. The predicted absolute lifetime
      attributable risks of SMN incidence were 11.4% after PBT and 19.2% after IMRT.
      The results of this study suggest that using proton beams instead of photon beams
      for radiotherapy may reduce the risk of SMN incidence for some HCC patients.

PMID- 21076200
TI  - Dose error analysis for a scanned proton beam delivery system.
AB  - All particle beam scanning systems are subject to dose delivery errors due to
      errors in position, energy and intensity of the delivered beam. In addition,
      finite scan speeds, beam spill non-uniformities, and delays in detector, detector
      electronics and magnet responses will all contribute errors in delivery. In this
      paper, we present dose errors for an 8 * 10 * 8 cm(3) target of uniform water
      equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy.
      Lower doses are also analyzed and presented later in the paper. Beam energy
      errors and errors due to limitations of scanning system hardware have been
      included in the analysis. By using Gaussian shaped pencil beams derived from
      measurements in the research room of the James M Slater Proton Treatment and
      Research Center at Loma Linda, CA and executing treatment simulations multiple
      times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in
      the target. These errors were calculated by delivering multiple treatments to the
      same volume and calculating the rms variation in delivered dose at each voxel in
      the target. The variations in dose were the result of random beam delivery errors
      such as proton energy, spot position and intensity fluctuations. The results show
      that with reasonable assumptions of random beam delivery errors, the spot
      scanning technique yielded an rms dose error in each voxel less than 2% or 3% of
      the 2 Gy prescribed dose. These calculated errors are within acceptable clinical
      limits for radiation therapy.

PMID- 21076201
TI  - Linking probe thermodynamics to microarray quantification.
AB  - Understanding the difference in probe properties holds the key to absolute
      quantification of DNA microarrays. So far, Langmuir-like models have failed to
      link sequence-specific properties to hybridization signals in the presence of a
      complex hybridization background. Data from washing experiments indicate that the
      post-hybridization washing has no major effect on the specifically bound targets,
      which give the final signals. Thus, the amount of specific targets bound to
      probes is likely determined before washing, by the competition against
      nonspecific binding. Our competitive hybridization model is a viable alternative
      to Langmuir-like models.

PMID- 21076203
TI  - From network structure to network reorganization: implications for adult
      neurogenesis.
AB  - Networks can be dynamical systems that undergo functional and structural
      reorganization. One example of such a process is adult hippocampal neurogenesis,
      in which new cells are continuously born and incorporate into the existing
      network of the dentate gyrus region of the hippocampus. Many of these introduced
      cells mature and become indistinguishable from established neurons, joining the
      existing network. Activity in the network environment is known to promote birth,
      survival and incorporation of new cells. However, after epileptogenic injury,
      changes to the connectivity structure around the neurogenic niche are known to
      correlate with aberrant neurogenesis. The possible role of network-level changes
      in the development of epilepsy is not well understood. In this paper, we use a
      computational model to investigate how the structural and functional outcomes of
      network reorganization, driven by addition of new cells during neurogenesis,
      depend on the original network structure. We find that there is a stable network
      topology that allows the network to incorporate new neurons in a manner that
      enhances activity of the persistently active region, but maintains global network
      properties. In networks having other connectivity structures, new cells can
      greatly alter the distribution of firing activity and destroy the initial
      activity patterns. We thus find that new cells are able to provide focused
      enhancement of network only for small-world networks with sufficient inhibition.
      Network-level deviations from this topology, such as those caused by
      epileptogenic injury, can set the network down a path that develops toward
      pathological dynamics and aberrant structural integration of new cells.

PMID- 21076205
TI  - Modelling a full scale membrane bioreactor using Activated Sludge Model No.1:
      challenges and solutions.
AB  - A full-scale membrane bioreactor (1,600 m(3) d(-1)) was monitored for modelling
      purposes during the summer of 2006. A complete calibration of the ASM1 model is
      presented, in which the key points were the wastewater characterisation, the
      oxygen transfer and the biomass kinetics. Total BOD tests were not able to
      correctly estimate the biodegradable fraction of the wastewater. Therefore the
      wastewater fractionation was identified by adjusting the simulated sludge
      production rate to the measured value. MLVSS and MLSS were accurately predicted
      during both calibration and validation periods (20 and 30 days). Because the
      membranes were immerged in the aeration tank, the coarse bubble and fine bubble
      diffusion systems coexisted in the same tank. This allowed five different
      aeration combinations, depending whether the 2 systems were operating separately
      or simultaneously, and at low speed or high speed. The aeration control
      maintained low DO concentrations, allowing simultaneous nitrification and
      denitrification. This made it difficult to calibrate the oxygen transfer. The
      nitrogen removal kinetics were determined using maximum nitrification rate tests
      and an 8-hour intensive sampling campaign. Despite the challenges encountered, a
      calibrated set of parameters was identified for ASM1 that gave very satisfactory
      results for the calibration period. Matching simulated and measured data became
      more difficult during the validation period, mainly because the dominant aeration
      configuration had changed. However, the merit of this study is to be the first
      effort to simulate a full-scale MBR plant.

PMID- 21076206
TI  - Enhanced treatment of endocrine disrupting chemicals by a granular bed
      electrochemical reactor.
AB  - Continuous treatments of trace endocrine disrupting chemicals (EDCs) such as
      17beta-estradiol (E2), bisphenol-A, nonylephenol, 4-t-octyl phenol and
      pentachlorophenol were carried out using a granular bed electrolytic reactor.
      Experimental results showed that the EDCs were removed by the reactor over 150
      days and removal efficiencies were nearly the same in the presence and absence of
      humic substance. Energy consumption for the treatment was around several Wh/m(3).
      For longer operation or higher loading conditions, Fenton oxidation was effective
      to regenerate electrodes. Calculated results by a mathematical model developed
      assuming liquid film mass-transfer as a rate-limiting step were in good agreement
      with observed results. Based on the model, enhancement of reactor performance was
      discussed.

PMID- 21076204
TI  - Collective cell motion in endothelial monolayers.
AB  - Collective cell motility is an important aspect of several developmental and
      pathophysiological processes. Despite its importance, the mechanisms that allow
      cells to be both motile and adhere to one another are poorly understood. In this
      study we establish statistical properties of the random streaming behavior of
      endothelial monolayer cultures. To understand the reported empirical findings, we
      expand the widely used cellular Potts model to include active cell motility. For
      spontaneous directed motility we assume a positive feedback between cell
      displacements and cell polarity. The resulting model is studied with computer
      simulations and is shown to exhibit behavior compatible with experimental
      findings. In particular, in monolayer cultures both the speed and persistence of
      cell motion decreases, transient cell chains move together as groups and velocity
      correlations extend over several cell diameters. As active cell motility is
      ubiquitous both in vitro and in vivo, our model is expected to be a generally
      applicable representation of cellular behavior.

PMID- 21076207
TI  - Incremental sanitation improvement strategy: comparison of options for Hanoi,
      Vietnam.
AB  - Urban sanitation issues should be tackled strategically, and may be addressed
      effectively when sewage development is pursued in conjunction with complementary
      sanitation measures. Five sanitation improvement scenarios employing sewage,
      night-soil collection-and-treatment (NSCT) system, and/or septic-tank improvement
      by annual dislodging were analyzed from the perspective of COD loads, total
      nitrogen loads, and cost under the conditions found in Hanoi, Vietnam. Compared
      to the development of sewage alone, the scenario of developing NSCT systems in a
      complementary manner with sewage development was estimated to be the most
      effective for a rapid decrease of both COD and total nitrogen loads. However, it
      may be difficult in some cases to replace ordinary water-flush toilet by the
      micro-flush toilet that are used in NSCT systems. In this case, the scenario
      employing septic-tank improvement in conjunction with sewage development may be
      effective for a rapid decrease of COD in locations where septic tanks are widely
      used under poor maintenance conditions and nitrogen pollution is not serious
      compared to COD. It was calculated that the two scenarios above would
      respectively require cost increases of 16 and 22% over the sewage development
      scenario.

PMID- 21076208
TI  - Tracking biological pollution sources using PCR-DGGE technology at Ta-An Beach.
AB  - The environmental authority of Taiwan has announced that ocean quality standard
      A, with E. coli less than 1,000 CFU/100 mL is safe for swimming. Ta-An Beach in
      central Taiwan was found to have exceeded 1,000 CFU/100 mL, which is 51% of the
      total monitoring records. Sewage, piggery and duck wastewater are discharged
      directly into this area. The traditional pollution source trace methods did not
      clearly identify the pollution source. This study used PCR-DGGE technology to
      establish micro-organisms fingerprints from water samples using comparative
      analysis with microbiological composition, and then determined the possible
      sources of biological contamination. The E. coli colonies at all samples were
      processed using linear regression analysis and compared with each other. The R(2)
      is 0.4102-0.7387 for the livestock farm and beach. This shows a positively
      relation. The piggery impact is more obvious. The beach microbial communities
      exhibited high similarity with piggery wastewater from the upstream region. We
      confirmed that the major pollution source for Ta-An Beach comes from piggery
      wastewater. The proposed method has high stability and reliability. It can be
      used as the basis for rapid identification of pollution sources at other beach
      water sites in the future.

PMID- 21076209
TI  - Urban pluvial flooding in Jakarta: applying state-of-the-art technology in a data
      scarce environment.
AB  - Available data relating to major pluvial flooding events in Jakarta, Indonesia
      were used to investigate the suitability of two different levels of
      sophistication in urban modelling tools for modelling these events. InfoWorks CS
      v9.0 was employed to build 1D and 1D/2D models of a 541 ha area of inner city
      Ciliwung River catchment which has a history of being particularly badly affected
      by flooding during heavy rainfall events. The study demonstrated that a 1D model
      was sufficient to simulate the flood extent of a major event using the limited
      data available. While the 1D/2D model also performed well, more data and time
      would have been required to match the 1D model's simulation of flood extent. Much
      more detailed data would have been required to produce reliable results in the
      1D/2D model and to enable any kind of verification or calibration of the two
      models beyond visual comparison with crude flood extent maps.

PMID- 21076210
TI  - Benchmarking energy consumption in municipal wastewater treatment plants in
      Japan.
AB  - Reduction of greenhouse gas (GHG) emissions is one of the most important tasks
      facing municipal WWTPs. Electric power consumption typically accounts for about
      90% of the total energy consumption. This study presents a benchmarking analysis
      of electric power consumption. The specific power consumption (SPC) ranged from
      0.44 to 2.07 kWh/m(3) for oxidation ditch plants and from 0.30 to 1.89 kWh/m(3)
      for conventional activated sludge plants without sludge incineration. Observed
      differences of the SPC can be attributed to the difference in the scale of plants
      rather than to different kinds of wastewater treatment processes. It was
      concluded that economical benefits by centralizing treatment had contributed
      significantly to the reduction of energy consumption. Further analysis was
      carried out on the plant that had shown an extremely small SPC value of 0.32
      kWh/m(3). In this WWTP, a large amount of digestion gas was generated by
      anaerobic digestion. In particular, it was used to generate power using
      phosphoric acid fuel cells to generate approximately 50% of the energy consumed
      in the plant. It was calculated that this plant had reduced the overall SPC by
      0.17 kWh/m(3). The effect of power generation using digestion gas demonstrated
      clearly the advantage of implementing energy recovery schemes.

PMID- 21076212
TI  - Quantitative structure property relationships for the adsorption of
      pharmaceuticals onto activated carbon.
AB  - Isotherms were determined for the adsorption of five pharmaceutical residues,
      primidone, carbamazepine, ibuprofen, naproxen and diclofenac, to Calgon
      Filtrasorb 300 powdered activated carbon (PAC). The sorption behavior was
      examined in ultra-pure and wastewater effluent organic matter (EfOM) matrices,
      where more sorption was observed in the ultra-pure water for PAC doses greater
      than 10 mg/L suggesting the presence of EfOM hinders the sorption of the
      pharmaceuticals to the PAC. Adsorption behaviors were described by the Freundlich
      isotherm model. Quantitative structure property relationships (QSPRs) in the form
      of polyparameter linear solvation energy relationships were developed for
      simulating the Freundlich adsorption capacity in both ultra-pure and EfOM
      matrices. The significant 3D-based descriptors for the QSPRs were the molar
      volume, polarizability and hydrogen-bond donor parameters.

PMID- 21076211
TI  - Use of cooling tower blow down in ethanol fermentation.
AB  - Reducing water consumption in bioethanol production conserves an increasingly
      scarce natural resource, lowers production costs, and minimizes effluent
      management issues. The suitability of cooling tower blow down water for reuse in
      fermentation was investigated as a means to lower water consumption. Extensive
      chemical characterization of the blow down water revealed low concentrations of
      toxic elements and total dissolved solids. Fermentation carried out with cooling
      tower blow down water resulted in similar levels of ethanol and residual glucose
      as a control study using deionized water. The study noted good tolerance by yeast
      to the specific scale and corrosion inhibitors found in the cooling tower blow
      down water. This research indicates that, under appropriate conditions, reuse of
      blow down water from cooling towers in fermentation is feasible.

PMID- 21076213
TI  - Nonpoint-source nitrogen and phosphorus behavior and modeling in cold climate: a
      review.
AB  - Pollution from nonpoint-source (NPS) nitrogen (N) and phosphorus (P) are the main
      causes of eutrophication in lotic, lentic and coastal systems. The climate of
      cold regions might play an important role in disturbing environmental behavior of
      NPS N and P, influencing simulation of watershed scale hydrologic and nonpoint
      source pollution models. The losses of NPS N and P increase in regions of cold
      climate. In cold seasons, accumulations of N and P are accelerated in soil with
      increasing fine root and aboveground biomass mortality, decreasing plant nutrient
      uptake, as well as freezing soil. N and P transformation is disturbed by soil
      frost and snow. Moreover, factors such as physical disruption of soil aggregates,
      pollutant accumulation in snowpack, and snow melting can all increase the NPS N
      and P losses to the waterbody. Therefore, NPS N and P in first flush are more
      serious in cold climate. All these effects, especially frozen soil and snowpack,
      make great challenges to watershed scale hydrologic and nonpoint-source pollution
      models simulation in cold climate. Model improvements of snowmelt runoff,
      nutrient losses in frozen soil, as well as N and P behavior have been initiated
      and will be continued to evaluate in terms of their performances and suitability
      with different scale, hydrologic and geologic conditions in the future.

PMID- 21076214
TI  - Sulfide removal from industrial wastewaters by lithotrophic denitrification using
      nitrate as an electron acceptor.
AB  - Sulfide is present in wastewaters as well as in biogas and can be removed by
      several physicochemical and biotechnological processes. Nitrate is a potential
      electron acceptor, readily available in most wastewater treatment plants and it
      can replace oxygen under anoxic conditions. A lab-scale reactor was operated for
      treatment of sulfide containing wastewater with nitrate as an electron acceptor
      and is used to evaluate the effects of volumetric loading rates, hydraulic
      retention time (HRT) and substrate concentrations on the performance of the
      lithotrophic denitrification process for treating industrial fermentation
      wastewaters. Sulfide is removed more than 90% at the loading rates between 0.055
      and 2.004 kg S(-2)/m(3) d, when the influent sulfide concentration is kept around
      0.163 kg/m(3) and the HRT decreased from 86.4 to 2 h. Nitrogen removal differed
      between 23 and 99% with different influent NO(3)(-)-N concentration and loading
      rates of NO(3)(-)/S(-2) ratio. The stoichiometry of sulfide oxidation with
      nitrate is calculated assuming different end-products based on thermodynamic
      approach and compared with experimental yield values. The calculated maximum
      volumetric and specific sulfide oxidation rates reached 0.076 kg S(-2)/m(3) h and
      0.11 kg S(-2)/kg VSS h, respectively. The results are obtained at industrially
      relevant conditions and can be easily adapted to either biogas cleaning process
      or to sulfide containing effluent streams.

PMID- 21076215
TI  - Valuable product production from wood mill effluents.
AB  - Fibreboard production is one of the most important industrial activities in
      Galicia (Spain). Great amounts of wastewater are generated, with properties
      depending on the type of wood, treatment process, final product and water
      reusing, among others. These effluents are characterized by a high chemical
      oxygen demand (COD), low pH and nutrients limitation. Aerobic and anaerobic
      processes have been used for their treatment. Presently, bioplastics production
      (mainly polyhydroxyalkanoates or PHA) from wastewaters with mixed cultures is
      being studied. Substrate requirements for these processes are a high organic
      matter content and low nutrient concentration. Therefore, wood mill effluents
      could be a suitable feedstock. PHA production from wastewaters is carried out in
      three steps. First, complex organic matter is converted into volatile fatty acids
      (VFA) through acidogenic fermentation. Then, VFA are used as substrate in an
      aerobic sequencing batch reactor (SBR), in which the enrichement of PHA producing
      bacteria from a mixed culture is favoured. Finally, the sludge from the SBR is
      fed with a pulse containing high VFA concentrations, resulting in PHA
      accumulation inside the cells. In this work, the possibility of applying this
      process to wood mill effluents is proposed. An acidification percentage of 37%
      and a storage yield (Y(STO)) of 0.23 Cmmol/Cmmol were obtained.

PMID- 21076216
TI  - Receiving water quality assessment: comparison between simplified and detailed
      integrated urban modelling approaches.
AB  - Urban water quality management often requires use of numerical models allowing
      the evaluation of the cause-effect relationship between the input(s) (i.e.
      rainfall, pollutant concentrations on catchment surface and in sewer system) and
      the resulting water quality response. The conventional approach to the system
      (i.e. sewer system, wastewater treatment plant and receiving water body),
      considering each component separately, does not enable optimisation of the whole
      system. However, recent gains in understanding and modelling make it possible to
      represent the system as a whole and optimise its overall performance. Indeed,
      integrated urban drainage modelling is of growing interest for tools to cope with
      Water Framework Directive requirements. Two different approaches can be employed
      for modelling the whole urban drainage system: detailed and simplified. Each has
      its advantages and disadvantages. Specifically, detailed approaches can offer a
      higher level of reliability in the model results, but can be very time consuming
      from the computational point of view. Simplified approaches are faster but may
      lead to greater model uncertainty due to an over-simplification. To gain insight
      into the above problem, two different modelling approaches have been compared
      with respect to their uncertainty. The first urban drainage integrated model
      approach uses the Saint-Venant equations and the 1D advection-dispersion
      equations, for the quantity and for the quality aspects, respectively. The second
      model approach consists of the simplified reservoir model. The analysis used a
      parsimonious bespoke model developed in previous studies. For the uncertainty
      analysis, the Generalised Likelihood Uncertainty Estimation (GLUE) procedure was
      used. Model reliability was evaluated on the basis of capacity of globally
      limiting the uncertainty. Both models have a good capability to fit the
      experimental data, suggesting that all adopted approaches are equivalent both for
      quantity and quality. The detailed model approach is more robust and presents
      less uncertainty in terms of uncertainty bands. On the other hand, the simplified
      river water quality model approach shows higher uncertainty and may be unsuitable
      for receiving water body quality assessment.

PMID- 21076217
TI  - Electrochemical removal of pentachlorophenol in a lab-scale platinum
      electrolyzer.
AB  - This study is focused on the removal of pentachlorophenol from its aqueous phase
      by electrochemically induced degradation with Pt electrodes. The objective of
      this study was to contrast the electrochemical removal of pentachlorophenol at
      the oxidative and the reductive potentials, and further to understand how to
      apply the electrochemical treatment on PCP degradation. Lab experiments were
      conducted in a Pt electrolyzer, and the voltage source was supplied and precisely
      controlled by an electrochemical analyzer. In these experiments, the variables
      including electrolyte species, pH, voltage supply, and reaction time were
      examined to compare the efficiency of pentachlorophenol removal. Experimental
      results showed that pentachlorophenol was completely degraded after being
      electrolyzed for 1 h at-1.5 V in a 0.5 M KCl solution, while the removal of
      pentachlorophenol is negligible under the similar condition when 0.5 M NaNO(3) or
      Na(2)CO(3) was used as the electrolyte. The electrolyte concentration below 0.5 M
      is unfavourable for the electrochemical removal of pentachlorophenol. The removal
      efficiency of pentachlorophenol is slightly affected by pH, and the strong basic
      environment might impede the degradation of pentachlorophenol. Comparing with
      those under positive potentials, the experiments conducted under negative
      potentials have shown a better removal of pentachlorophenol with a higher current
      efficiency. It implies that pentachlorophenol degradation followed the reductive
      pathway. Based on the analysis of GC/MS, the intermediates of pentachlorophenol
      degradation were identified as 1,2-dichlorocyclohexane and 2-chlorocyclohexanol.

PMID- 21076218
TI  - Feasibility of an electrochemically assisted Fenton method using Fe(2 +)/HOCl
      system as an advanced oxidation process.
AB  - The feasibility of an electrochemically assisted Fenton treatment using a Fenton
      type reaction of ferrous iron (Fe(2 + )) and hypochlorous acid (HOCl) is
      discussed in this research. The reactor used was composed of an undivided single
      cell with a ruthenium dioxide-coated titanium anode and a stainless steel
      cathode, in which Fe(2 + ) and HOCl were catalytically regenerated from ferric
      iron at the cathode and chloride ion at the anode, respectively. Although the
      reactor functioned well, the degradation rate of 1,4-dioxane as a hydroxyl
      radical probe decreased at the current density more than 6.92 mA cm(-2). The
      decrease in degradation rate was inferred to be caused by the vain consumption of
      hydroxyl radicals by excess HOCl and the deposition of ferric hydroxide on the
      cathode at relatively high current density. The current efficiency of 1,4-dioxane
      removal remained more than 90% at the current density less than 6.92 mA cm(-2)
      and the iron concentration not less than 1.0 mmol L(-1). Consequently, this
      technique is thought to be applicable to the treatment of wastewater containing
      high concentration of chloride ion such as landfill leachate, scrubber wastewater
      from incineration plants, etc.

PMID- 21076219
TI  - Minimizing health risks during secondary effluent application via subsurface drip
      irrigation.
AB  - Health risks posed on consumers due to the use of agricultural products irrigated
      with reclaimed wastewater were assessed by numerical simulation. The analysis is
      based on defining of an Exposure Model (EM) which takes into account several
      parameters: (i) the quality of the applied wastewater, (ii) the irrigation
      method, (iii) the elapsed times between irrigation, harvest, and product
      consumption, and; (iv) the consumers' habits. The exposure model is used for
      numerical simulation of human consumers' risks by running the Monte Carlo
      simulation method. Although some deviations in the numerical simulation which are
      probably due to uncertainty (impreciseness in quality of input data) and
      variability due to diversity among populations reasonable results were accepted.
      Accordingly, there is a several orders of magnitude difference in the risk of
      infection between the different exposure scenarios with the same water quality.
      The variability indicates the need for setting risk-based criteria for wastewater
      reclamation, including the application method and environmental conditions,
      rather than single water quality guidelines. Extra data is required to decrease
      uncertainty in the risk assessment. Future research needs to include definite
      acceptable risk criteria, more accurate dose-response modeling, information
      regarding pathogen survival in treated wastewater, additional data related to the
      passage of pathogens into and in the plants during irrigation, and information
      referring to the consuming habits of the human community.

PMID- 21076220
TI  - Managed aquifer recharge: rediscovering nature as a leading edge technology.
AB  - Use of Managed Aquifer Recharge (MAR) has rapidly increased in Australia, USA,
      and Europe in recent years as an efficient means of recycling stormwater or
      treated sewage effluent for non-potable and indirect potable reuse in urban and
      rural areas. Yet aquifers have been relied on knowingly for water storage and
      unwittingly for water treatment for millennia. Hence if 'leading edge' is defined
      as 'the foremost part of a trend; a vanguard', it would be misleading to claim
      managed aquifer recharge as a leading edge technology. However it has taken a
      significant investment in scientific research in recent years to demonstrate the
      effectiveness of aquifers as sustainable treatment systems to enable managed
      aquifer recharge to be recognised along side engineered treatment systems in
      water recycling. It is a 'cross-over' technology that is applicable to water and
      wastewater treatment and makes use of passive low energy processes to
      spectacularly reduce the energy requirements for water supply. It is robust
      within limits, has low cost, is suitable from village to city scale supplies, and
      offers as yet almost untapped opportunities for producing safe drinking water
      supplies where they do not yet exist. It will have an increasingly valued role in
      securing water supplies to sustain cities affected by climate change and
      population growth. However it is not a universal panacea and relies on the
      presence of suitable aquifers and sources of water together with effective
      governance to ensure human health and environment protection and water resources
      planning and management. This paper describes managed aquifer recharge,
      illustrates its use in Australia, outlining economics, guidelines and policies,
      and presents some of the knowledge about aquifer treatment processes that are
      revealing the latent value of aquifers as urban water infrastructure and provide
      a driver to improving our understanding of urban hydrogeology.

PMID- 21076221
TI  - Modelling sewer sediment deposition, erosion, and transport processes to predict
      acute influent and reduce combined sewer overflows and CO(2) emissions.
AB  - Understanding of solids deposition, erosion, and transport processes in sewer
      systems has improved considerably in the past decade. This has provided guidance
      for controlling sewer solids and associated acute pollutants to protect the
      environment and improve the operation of wastewater systems. Although measures to
      decrease combined sewer overflow (CSO) events have reduced the amount of
      discharged pollution, overflows continue to occur during rainy weather in
      combined sewer systems. The solution lies in the amount of water allotted to
      various processes in an effluent treatment system, in impact evaluation of water
      quality and prediction technology, and in stressing the importance of developing
      a control technology. Extremely contaminated inflow has been a serious research
      subject, especially in connection with the influence of rainy weather on nitrogen
      and organic matter removal efficiency in wastewater treatment plants (WWTP). An
      intensive investigation of an extremely polluted inflow load to WWTP during rainy
      weather was conducted in the city of Matsuyama, the region used for the present
      research on total suspended solid (TSS) concentration. Since the inflow during
      rainy weather can be as much as 400 times that in dry weather, almost all sewers
      are unsettled and overflowing when a rain event is more than moderate. Another
      concern is the energy consumed by wastewater treatment; this problem has become
      important from the viewpoint of reducing CO(2) emissions and overall costs.
      Therefore, while establishing a prediction technology for the inflow water
      quality characteristics of a sewage disposal plant is an important priority, the
      development of a management/control method for an effluent treatment system that
      minimises energy consumption and CO(2) emissions due to water disposal is also a
      pressing research topic with regards to the quality of treated water. The
      procedure to improve water quality must make use of not only water quality and
      biotic criteria, but also modelling systems to enable the user to link the effect
      of changes in urban sewage systems with specific quality, energy consumption,
      CO(2) emission, and ecological improvements of the receiving water.

PMID- 21076222
TI  - Physicochemical treatment of office and public buildings greywater.
AB  - The current study analyses the performance of deep sand filtration of greywater
      from an office building and the performance of a combined physicochemical process
      comprising of coagulation, sedimentation and filtration. Raw greywater quality
      exhibited very high variability with average turbidity of 35 NTU, and TSS,
      COD(t), and BOD of 45, 240, 75 mg/l respectively. The stand-alone filter removed
      50 and 70% of the turbidity and TSS, but failed to remove COD and BOD. Quality of
      the produced effluent was too low to allow any reuse. Clogging rate of the filter
      was high and under hydraulic loading of 3-4 m(3)/(m(2) h) the filtration cycle
      had to be terminated after 5-8 h. Clogging occurred mainly on the upper layer,
      indicating the dominance of "cake" filtration mechanism. Addition of coagulation
      and sedimentation prior to sedimentation dramatically improved effluent quality,
      reaching overall removal efficiencies of 92, 94, 65 and 57% of turbidity, TSS
      COD(t) and BOD respectively. The filtration cycle could be prolonged to 20 h. The
      effluent produced was of much better quality, yet, it has to be further treated
      (either biological treatment or membrane filtration). Most of the removal
      occurred in the coagulation-sedimentation step, while the filter acted as a
      polishing unit.

PMID- 21076223
TI  - Energy efficient aeration of wastewaters from the pulp and paper industry.
AB  - More than 50% of the electrical power needed to treat pulp and paper industry
      effluents is used for aeration in biological treatment stages. A large share of
      the oxygen that passes through the wastewater is not consumed and will be found
      in the off-gas. Energy can be saved by aerating under conditions where the oxygen
      transfer is most efficient, for example at low concentrations of dissolved oxygen
      Consider the sludge as an energy source; electricity can be saved by avoiding
      sludge reduction through prolonged aeration. High oxygen transfer efficiency can
      be retained by using the oxygen consumption of biosolids. Quantified savings in
      the form of needed volumes of air while still achieving sufficient COD reduction
      are presented. The tests have been made in a bubble column with pulp mill process
      water and sludge from a biological treatment plant. These were supplemented with
      case studies at three pulp and paper mills.

PMID- 21076224
TI  - Water treatment technology for produced water.
AB  - Large amounts of produced water are generated during oil and gas production.
      Produced water, as it is known in the oil industry, is briny fluid trapped in the
      rock of oil reservoirs. The objective of this study was to test produced waters
      from a Montana USA oilfield using a mobile station to design a plant to cost
      efficiently treat the produced water for agricultural irrigation. We used
      combined physical and chemical treatment of produced water in order to comply
      with reuse and discharge limits. This mobile station consists of three stages:
      pretreatments, membrane filtration and post treatment. Two spiral-wound membrane
      units were employed and the rejections of various constituents were examined. The
      performance of two membranes, 20 kDa weight cut-off (MWCO) ultrafiltration and a
      polyamide-composite reverse osmosis membrane was investigated. The mobile station
      effectively decreased conductivity by 98%, COD by 100% and the SAR by 2.15
      mgeqv(0.5) in the produced water tested in this study. Cost analysis showed that
      the treatment cost of produced water is less expensive than to dispose of it by
      injection and this treated water may be of great value in water-poor regions. We
      can conclude that the mobile station provided a viable and cost-effective result
      to beneficial use of produced water.

PMID- 21076225
TI  - CFD modelling of flow field and particle tracking in a hydrodynamic stormwater
      separator.
AB  - The best management practices (BMPs) for control of urban stormwater pollution
      are evaluated to remove solid particles containing various pollutants. Currently,
      most storm runoff treatment devices using primary pollutant removal mechanism are
      applied to storm water since most pollutants in runoff are associated with the
      solid particulates. A hydrodynamic separator is a storm water treatment device
      using centrifugal motion which separates solids pollution from runoff. In this
      study, the velocity flow field and particle tracking of hydrodynamic separator
      were investigated using anthracite as a computational fluid dynamics (CFD) model
      particle. The Fluent 6.3.26 CFD program was used to predict the solid particles
      removal efficiency for various parameters such as particle size, surface loading
      rate, and the ratio of underflow to overflow. The velocity flow field in a
      hydrodynamic stormwater separator (HDS) has been simulated using CFD RNG kappa
      epsilon model. Modeling results for the removal efficiency of HDS were similar
      with the results obtained from experimental measurements of laboratory scale HDS.
      These results showed that the simulated velocity field was useful to interpret
      the behavior of flow in the hydrodynamic separator. The results obtained from
      particle tracking can be applied to predict the separation efficiency.

PMID- 21076226
TI  - A mesocosm study using four native Hawaiian plants to assess nitrogen
      accumulation under varying surface water nitrogen concentrations.
AB  - Accumulation of nitrogen (N) by native Hawaiian riparian plants from surface
      water was measured under a controlled experimental mesocosm setting. Four
      species, Cladium jamaicense, Cyperus javanicus, Cyperus laevigatus, and Cyperus
      polystachyos were tested for their ability to survive in coconut fiber coir log
      media with exposure to differing N concentrations. It was hypothesized that the
      selected species would have significantly different tissue total nitrogen (TN)
      concentrations, aboveground biomass, and TN accumulation rates because of habitat
      preference and physiological growth differences. A general linear model (GLM)
      analysis of variance (ANOVA) determined that species differences accounted for
      the greatest proportion of variance in tissue TN concentration, aboveground
      biomass growth, and accumulation rates, when compared with the other main effects
      (i.e. N concentration, time) and their interactions. A post hoc test of means
      demonstrated that C. jamaicense had significantly higher tissue TN concentration,
      aboveground biomass growth, and accumulation rates than the other species under
      all N concentrations. It was also hypothesized that tissue TN concentrations and
      biomass growth would increase in plants exposed to elevated N concentrations,
      however data did not support this hypothesis. Nitrogen accumulation rates by
      species were controlled by differences in plant biomass growth.

PMID- 21076228
TI  - Constructed wetland for water quality improvement: a case study from Taiwan.
AB  - In Taiwan, more than 20% of the major rivers are mildly to heavily polluted by
      domestic, industrial, and agricultural wastewaters due to the low percentage of
      sewers connected to wastewater treatment plants. Thus, constructed or engineered
      wetlands have been adopted as the major alternatives to clean up polluted rivers.
      Constructed wetlands are also applied as the tertiary wastewater treatment
      systems for the wastewater polishment to meet water reuse standards with lower
      operational costs. The studied Kaoping River Rail Bridge Constructed Wetland
      (KRRBCW) is the largest constructed wetland in Taiwan. It is a multi-function
      wetland and is used for polluted creek water purification and secondary
      wastewater polishment before it is discharged into the Kaoping River. Although
      constructed wetlands are feasible for contaminated water treatment, wetland
      sediments are usually the sinks for organics and metals. In this study, water and
      sediment samples were collected from the major wetland basins in KRRBCW. The
      investigation results show that more than 97% of total coliforms (TC), 55% of
      biochemical oxygen demand (BOD), and 30% of nutrients [e.g. total nitrogen (TN),
      total phosphorus (TP)] were removed via the constructed wetland system. However,
      results from the sediment analyses show that wetland sediments contained high
      concentrations of metals (e.g. Cu, Fe, Zn, Cr, and Mn), organic contents
      (sediment oxygen demand = 1.7 to 7.6 g O(2)/m(2) d), and nutrients (up to 18.7
      g/kg of TN and 1.22 g/kg of TN). Thus, sediments should be excavated periodically
      to prevent the release the pollutants into the wetland system and causing the
      deterioration of wetland water quality. Results of polymerase chain reaction
      (PCR), denaturing gradient gel electrophoresis (DGGE), and nucleotide sequence
      analysis reveal that a variation in microbial diversity in the wetland systems
      was observed. Results from the DGGE analysis indicate that all sediment samples
      contained significant amounts of microbial ribospecies, which might contribute to
      the carbon degradation and nitrogen removal. Gradual disappearance of E. coli was
      also observed along the flow courses through natural attenuation mechanisms.

PMID- 21076227
TI  - A performance indicators system for urban wastewater treatment plants.
AB  - A performance assessment system (PAS) is an important instrument to provide a
      cost-effective and sustainable management of wastewater treatment plants (WWTPs).
      Despite the fact that many PASs have been developed in recent years, important
      aspects of WWTP evaluation have not yet been considered. This paper presents the
      framework and the overall performance indicators of a PAS developed for urban
      WWTPs.

PMID- 21076229
TI  - A methodology to bridge the water information gap.
AB  - The metaphor of the water information gap is used to describe the discontent
      between information users and information producers about the use of and need for
      specific information. This paper describes the rugby-ball methodology for
      specification of information needs that was developed on the basis of an analysis
      of the water information gap and insights from the literature on policy- and
      decision-analysis, problem-structuring, and information management. The
      methodology consists of a process-architecture to manage the process of assessing
      information needs and a structure to organise the information needs related to
      water policy objectives. The methodology was developed and enhanced through a
      Reflection-in-Action process in which interaction between ideas and practice
      leads to improved results. The paper describes the methodology and its
      development, and concludes both on the development process and on the abilities
      of the methodology to narrow the water information gap.

PMID- 21076230
TI  - Anaerobic treatability and biogas production potential of selected in-mill
      streams.
AB  - Biochemical methane potential assays (BMP assays) were performed to study the
      potential of anaerobic treatment of in-mill wastewaters. The assay results
      indicated that condensate and the BCTMP effluent, which are currently treated
      with the anaerobic internal circulation reactors, were the best streams for
      anaerobic treatment because of their relatively high degradability (>80%) and
      initial rates of biogas production. The softwood dewatering process stream was
      the worst with the lowest degradability (~30%). The hardwood stream was more
      degradable than the softwood stream from the same process. Biogas production was
      found to be additive and predictable in blended samples. In addition,
      degradability was found to be negatively correlated to the concentration of
      dehydroabietic acid and tannin-lignin compounds. The anaerobic treatment of the
      suitable streams has great potential value with significantly reduced sludge
      production and energy savings.

PMID- 21076231
TI  - Studies on removal of chromium (VI) from water using chitosan coated Cyperus
      pangorei.
AB  - Environmental contamination by toxic heavy metals is a significant universal
      problem. The main objective of the study is to use a biodegradable materials like
      Cyperus pangorei and Chitosan as a composite biosorbent for the removal of Cr(VI)
      from water. The newly prepared biosorbent is characterized and the capacity of
      Cr(VI) removal of the biosorbent is carried out systematically by batch mode
      operations. The adsorption capacity of the biosorbent is examined by changing the
      parameters like biosorbent dose, varying the initial contact time, varying
      initial concentration of metal ion and pH of the metal ion solution to know the
      actual mechanism taking place during the initial sorption process. The
      experimental data obtained were fitted with the Freundlich, Langmuir and Redlich
      Peterson isotherm models and the pseudo first order and the pseudo second order
      kinetic models. Equilibrium data were fitted very well to the Langmuir Isotherm
      model and pseudo second order kinetic model. Desorption of the metal ion is also
      carried out using different concentration of NaOH.

PMID- 21076232
TI  - Modeling and verification of selective sludge discharge as the controlling factor
      for aerobic granulation.
AB  - Mathematical simulation and laboratory experiments were conducted to investigate
      the controlling factor for aerobic sludge granulation. A model was used to
      describe the biomass dynamics during the granulation process. The simulation
      results indicate that the selective discharge of small and loose sludge flocs is
      the key controlling factor for granulation. In the experimental studies, tests
      were conducted with four batch column reactors (BCR) that were seeded with both
      activated sludge flocs and mature granules. Three different sludge discharge
      methods were tested, including unselective discharge of mixed sludge, selective
      discharge of small and slow-settling flocs, and selective discharge of settled
      dense sludge. The results show that mixed sludge discharge and discharge of dense
      sludge resulted in disappearance of granules from the reactors. Only selective
      discharge of small and slow-settling sludge flocs led to complete granulation.
      Small and loose sludge flocs were found to have a clear advantage over large and
      dense granules in substrate uptake. It can be concluded that selective discharge
      of loose flocs removes these competitors in suspended-growth mode from the
      reactors and makes the substrate more available for uptake and utilization by the
      biomass in attached-growth form, leading to granulation.

PMID- 21076233
TI  - Fate of selected pharmaceuticals and personal care products after secondary
      wastewater treatment processes in Taiwan.
AB  - Pharmaceuticals and personal care products (PPCPs) constitute a class of
      chemicals of emerging concern due to the potential risks they pose to organisms
      and the environment, even at low concentrations (ng/L). Recent studies have found
      that PPCPs are not efficiently removed in secondary wastewater treatment plants
      (WWTPs). This study has: (1) simultaneously investigated the occurrence of sixty
      one PPCPs using solid phase extraction and high-performance liquid chromatography
      tandem mass spectrometry, (2) evaluated removal efficiencies of target PPCPs in
      six WWTPs that discharge effluents into major Taiwanese rivers, and lastly (3)
      examined matrix interference during analysis of target PPCPs in water samples.
      The twenty target PPCPs were chosen for their high detection frequencies, high
      influent concentrations, and stability during wastewater treatment processes.
      Caffeine and acetaminophen were detected at the highest concentrations (as high
      as 24,467 and 33,400 ng/L) and were effectively removed (both >96%); other PPCPs
      were detected in the high ng/L range but were not effectively removed. Matrix
      interference (by ion suppression or enhancement) during the analysis resulted in
      underestimation of the removal efficiencies of erythromycin-H(2)O, cefazolin,
      clarithromycin, ibuprofen, diclofenac, clofibric acid and gemfibrozil.

PMID- 21076234
TI  - Effect of heavy metal stress on emerging plants community constructions in
      wetland.
AB  - In this paper, we report the effects of heavy metals (HMs) (cadmium and mercury)
      on seed germination and seedling growth of Phragmites australis and Triarrhena
      sacchariflora, which are the two main typical emerging plants in Hongze Lake
      wetland. The results showed that there was a reduction in germination percentage,
      germination index and seedling length as HM concentration in the growing media
      increased for both treatments. The effect of HMs toxicity on seed germination and
      seedling growth of T. sacchariflora was more obvious than of P. australis. At the
      stage of seed germination, P. australis and T. sacchariflora were sensitive to
      Hg(2 + ) and Cd(2 + ), respectively, and Hg(2 + ) was more toxic than Cd(2 + ) at
      the stage of seedling growth. The effect of HMs toxicity is not invariable during
      plant growth. Compared to the stage of seedling growth, P. australis and T.
      sacchariflora are more susceptible to HMs at the stage of seed germination. In
      addition, we calculated the ecological thresholds of P. australis to Cd and Hg
      are 19.32 and 1.08 mg kg(-1), and that of T. sacchariflora to Cd is 4.62 mg kg(
      1) based on the lab simulation. The results also indicated that the species of P.
      australis is more tolerant than T. sacchariflora to the HMs and is a better
      candidate for restoration in Hongze Lake wetland ecosystem.

PMID- 21076235
TI  - Clinical features and management of ectopic ACTH syndrome at a single institute
      in Japan.
AB  - Ectopic ACTH syndrome (EAS) is a diagnostic challenge because it is often
      indistinguishable from Cushing's disease. We describe our series of EAS patients
      referred to us during 1992-2009. Among 16 cases (9 females / 7 males), with mean
      age of 58.4 +/- 19.0yr, the ectopic source was identified in ten (proven EAS),
      whereas unidentified in six (occult/unknown EAS). Their salient clinical
      manifestations included Cushingoid feature (88%), skin pigmentation (88%),
      profound hypokalemia (88%), hypertension (75%), diabetes/impaired glucose
      tolerance (75%), hyperlipidemia (69%), and severe infection (44%). Dynamic
      endocrine tests revealed markedly elevated plasma ACTH levels (211 +/- 116pg/mL)
      and cortisol levels (60.9 +/- 30.1ug/dL) which showed resistance to overnight
      high-dose (8mg) dexamethasone suppression test in 15 (94%) and unresponsiveness
      to CRH stimulation in 12 (75%). No ACTH gradient during inferior petrosal
      sampling was noted in 13 of 15 (87%). Imaging tests by CT/MRI identified the
      tumors in 8 of 16 (50%), in 4 of 11 (36%) and 4 of 6 (66.7%) octreotide
      responders by somatostatin receptor scintigraphy, but in only one of 9 (11.1%) by
      FDG-PET scan. Six cases deceased, including small cell carcinoma (2) and
      adenocarcinoma (1) of lung, neuroendocrine carcinoma of pancreas (1) and stomach
      (1), and olfactory neuroblastoma (1), whereas 4 cases survived after removal of
      the tumors, including bronchial carcinoid tumor (3) and thymic hyperplasia (1).
      Six occult/unknown EAS patients survived for 67.5 months after medical treatment
      with metyrapone to control hypercortisolism. Thus, various endocrine tests
      combined with imaging studies are required to correctly localize the tumors.
      Control of hypercortisolemia by metyrapone, even if tumor is unrecognized, is
      critical for better prognosis, and the long-term follow-up by repeated endocrine
      and imaging tests is mandatory.

PMID- 21076236
TI  - Liposome-encapsulated hemoglobin ameliorates impairment of fear memory and
      hippocampal dysfunction after cerebral ischemia in rats.
AB  - Liposome-encapsulated hemoglobin (LEH) has been developed as a blood substitute.
      In spite of its size (1/30 - 1/40 of erythrocytes), LEH has an oxygen-carrying
      capacity comparable to erythrocytes. Thus, LEH is expected to carry oxygen into
      vital organs via collateral routes during ischemia induced by vascular embolism.
      In the present study, we examined the therapeutic effects of LEH on behavioral
      impairments in rats after four-vessel occlusion (4VO) for 30 min. In the open
      field test, locomotor activity in 4VO rats did not alter 7 days after ischemia.
      However, in the contextual fear conditioning (CFC) test, the freezing rate was
      significantly decreased in 4VO rats, although no behavioral changes in the Y-maze
      test and elevated plus-maze test were observed. Phosphorylation of the cyclic AMP
      response element-binding protein (CREB) in the hippocampal CA1 region after the
      CFC test was attenuated. These 4VO-induced impairments were significantly
      alleviated by the administration of LEH (5 ml/kg, i.v.) during occlusion.
      Moreover, LEH did not alter hippocampal blood flow and tissue oxygen pressure
      during 4VO, but it did suppress hyperoxia after ischemia-reperfusion. These
      findings suggest that LEH, an artificial oxygen carrier, could be a novel
      therapeutic agent for brain dysfunction after acute cerebral ischemia.

PMID- 21076237
TI  - Methylglyoxal augments angiotensin II-induced contraction in rat isolated carotid
      artery.
AB  - Methylglyoxal (MGO), a metabolite of glucose, accumulates in vascular tissues of
      a hypertensive animal. In the present study, we examined the effect of MGO on
      angiotensin (Ang) II-induced contraction of rat carotid artery. Treatment of
      carotid artery with MGO (420 uM, 30 min) significantly augmented Ang II (0.1 to
      30 nM)-induced concentration-dependent contraction. The effect was abolished by
      the removal of endothelium. BQ-123 (1, 5 uM), an endothelin A-receptor blocker,
      had no effect on the MGO-induced enhancement of Ang II-induced contraction.
      AL8810 (1 uM), a prostaglandin F(2alpha)-receptor blocker, or SQ29548 (1 uM), a
      thromboxane A(2)-receptor blocker, was also ineffective. However, tempol (10 uM),
      a superoxide scavenger, and catalase (5000 U/mL), which metabolizes hydrogen
      peroxide to water, significantly prevented the effect of MGO. Combined MGO and
      Ang II treatment increased reactive oxygen species (ROS) production. Apocynin (10
      uM) or gp91ds-tat (3 uM), an inhibitor of nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase, significantly prevented the effect of MGO. Gp91ds-tat
      or an Ang II type 1-receptor (AT1R) blocker, losartan (10 uM), prevented the MGO
      mediated increased ROS production. The present study revealed that MGO augments
      Ang II-induced contraction by increasing AT1R-mediated NADPH oxidase-derived
      superoxide and hydrogen peroxide production in endothelium of rat carotid artery.

PMID- 21076239
TI  - Bibliography--Editors' selection of current word literature.

PMID- 21076238
TI  - Complete disruption of all nitric oxide synthase genes causes markedly
      accelerated renal lesion formation following unilateral ureteral obstruction in
      mice in vivo.
AB  - The role of nitric oxide (NO) derived from all three NO synthases (NOSs) in renal
      lesion formation remains to be fully elucidated. We addressed this point in mice
      lacking all NOSs. Renal injury was induced by unilateral ureteral obstruction
      (UUO). UUO caused significant renal lesion formation (tubular apoptosis,
      interstitial fibrosis, and glomerulosclerosis) in wild-type, singly, and triply
      NOS(-/-) mice. However, the extents of renal lesion formation were markedly and
      most accelerated in the triply NOS(-/-) genotype. UUO also elicited the
      infiltration of inflammatory macrophages, up-regulation of transforming growth
      factor (TGF)-beta1, and induction of epithelial mesenchymal transition (EMT) in
      all of the genotypes; however, the extents were again largest by far in the
      triply NOS(-/-) genotype. Importantly, long-term treatment with the angiotensin
      II type 1 (AT(1))-receptor blocker olmesartan significantly prevented the
      exacerbation of those renal structural changes after UUO in the triply NOS(-/-)
      genotype, along with amelioration of the macrophage infiltration, TGF-beta1
      levels, and EMT. These results provide the first evidence that the complete
      disruption of all NOS genes results in markedly accelerated renal lesion
      formation in response to UUO in mice in vivo through the AT(1)-receptor pathway,
      demonstrating the critical renoprotective role of all NOSs-derived NO against
      pathological renal remodeling.

PMID- 21076240
TI  - A brief remembrance of a life well lived: preface to the special section in
      tribute to Mark Ylvisaker--the importance of everyday people and contexts.

PMID- 21076241
TI  - A randomized trial of teen online problem solving for improving executive
      function deficits following pediatric traumatic brain injury.
AB  - OBJECTIVE: To examine the efficacy of teen online problem solving (TOPS) in
      improving executive function (EF) deficits following traumatic brain injury (TBI)
      in adolescence. METHODS: Families of adolescents (aged 11-18 years) with moderate
      to severe TBI were recruited from the trauma registry of 2 tertiary-care
      children's hospitals and then randomly assigned to receive TOPS (n = 20), a
      cognitive-behavioral, skill-building intervention, or access to online resources
      regarding TBI (Internet resource comparison; n = 21). Parent and teen reports of
      EF were assessed at baseline and a posttreatment follow-up (mean = 7.88 months
      later). RESULTS: Improvements in self-reported EF skills were moderated by TBI
      severity, with teens with severe TBI in the TOPS treatment reporting
      significantly greater improvements than did those with severe TBI in the Internet
      resource comparison. The treatment groups did not differ on parent ratings of EF
      at the follow up. CONCLUSIONS: Findings suggest that TOPS may be effective in
      improving EF skills among teens with severe TBI.

PMID- 21076242
TI  - Structured flexibility: the use of context-sensitive self-regulatory scripts to
      support young persons with acquired brain injury and behavioral difficulties.
AB  - OBJECTIVE: This study investigated the effects of a cognitive-behavioral
      intervention on the escalating behavior problems observed in 2 children with
      severe traumatic brain injury. DESIGN: Multiple baseline designs were used to
      document the effects of an intervention package that integrated cognitive and
      executive function interventions to address severe challenging behaviors in
      public school settings. MAIN OUTCOMES AND RESULTS: The results suggested that the
      intervention reduced the frequency and intensity of challenging behaviors and
      increased the quantity of work completed. CONCLUSIONS: These 2 successful single
      subject experiments expand the findings of previous studies on the use of a
      support-oriented intervention that uses context-sensitive, flexible
      cognitive/behavioral scripts combined with positive behavior interventions and
      supports to reduce challenging behaviors.

PMID- 21076243
TI  - Professional development in TBI for educators: the importance of context.
AB  - Effective instructional and behavioral support strategies implemented by trained
      educators can help mitigate the academic and behavioral challenges associated
      with childhood brain injury. However, the training provided by university teacher
      preparation programs is clearly inadequate, a problem that cuts across the
      professions that work with school-aged students. Educators need training in
      methods validated for students with traumatic brain injury (TBI) and in adapting
      strategies validated for students with other disabilities. Almost 10 years after
      Ylvisaker and colleagues proposed a research and professional development agenda
      in the area of teacher training, students with TBI continue to be underserved and
      underidentified for educational supports. Effective staff development practices
      for educators must include training in evidence-based interventions, supervised
      practice with new skills, and continued mentoring, feedback, and consultation in
      the school setting. Two models currently in use-the TBI Consulting Team and
      BrainSTARS models-incorporate those features. Preliminary evidence suggests that
      these models help teachers feel more prepared and knowledgeable in working with
      students with TBI. Given the urgent needs of students with TBI, validating these
      promising practices should be a high priority for the field of pediatric brain
      injury.

PMID- 21076245
TI  - Surgical hip dislocation for osteochondral transplantation as a salvage procedure
      for a femoral head impaction fracture.
AB  - Obturator anterior hip dislocation is very rare. Poor results are described in
      patients with additional large transchondral fractures and treatment of these
      injuries remains challenging. Appropriate treatment recommendations are missing
      in the literature. This case report introduces surgical hip dislocation for
      osteochondral autograft transplantation with graft harvest from the
      nonweightbearing area of the head-neck junction as a salvage procedure in a large
      femoral head defect. We report the treatment and outcome of a 48-year-old man who
      sustained an anterior dislocation of the left hip after a motorcycle accident.
      After initial closed reduction in the emergency room, imaging analysis revealed a
      large osteochondral defect of the femoral head within the weightbearing area (10
      * 20 mm, depth: 5 mm). The hip was exposed with a surgical hip dislocation using
      a trochanteric osteotomy. An osteochondral autograft was harvested from a
      nonweightbearing area of the femoral head and transferred into the defect. The
      patient was prospectively examined clinically and radiologically. Two years
      postoperatively, the patient was free of pain and complaints. The function of the
      injured hip was comparable to that of the contralateral, healthy hip and showed
      satisfying radiologic results. Surgical hip dislocation with a trochanteric flip
      osteotomy is a simple, one-step technique that allows full inspection of the hip
      to treat osteochondral femoral defects by osteochondral transplantation. The
      presented technique, used as a salvage procedure in a large femoral head defect,
      yielded good clinical and satisfying radiologic outcomes at the midterm.

PMID- 21076244
TI  - Executive Function in the Real World: BRIEF lessons from Mark Ylvisaker.
AB  - It is well established that brain injuries adversely affect the executive
      functions and their development. Mark Ylvisaker had a substantial impact on how
      we assess and treat children and adolescents with disrupted executive functions
      secondary to traumatic brain injury. He articulated core principles for effective
      assessment and intervention that emphasized the importance of real-world meaning
      and application. He taught us that assessment that captures a child's everyday
      functioning in the context of real-world demands is often more informative than
      traditional neuropsychological measures alone and that interventions that improve
      functioning in the real-world environment are most useful. His pragmatic model
      influenced our own efforts to measure executive function and to develop
      intervention systems for children with executive function deficits. This article
      reviews the development of the Behavior Rating Inventory for Executive Function
      as an approach to ecological assessment of children and adolescents with
      traumatic brain injury. As we take what we learned from Mark Ylvisaker, it
      becomes increasingly apparent that our assessment and intervention methods,
      especially as related to the executive functions, demand an everyday, real-world
      context.

PMID- 21076246
TI  - Cephalomedullary screws as the standard proximal locking screws for nailing
      femoral shaft fractures.
AB  - OBJECTIVES: In 2004, we modified our technique for the stabilization of femoral
      shaft fractures so that all fractures were stabilized using a reconstruction nail
      with proximal locking screws oriented into the femoral head. The rationale for
      this was twofold: first, potentially "missed" associated femoral neck fractures
      would be stabilized. Second, hip fractures that might occur later in life above
      the intramedullary nail might be avoided. The purpose of this study therefore was
      to determine whether there were any risks to patients treated for femoral shaft
      fractures with antegrade nails using cephalomedullary proximal locking screws.
      DESIGN: Retrospective. SETTING: Two regional trauma centers.
      PATIENTS/PARTICIPANTS: Eighty-seven consecutive patients were treated for a
      femoral shaft fracture treated with antegrade femoral nailing with a
      cephalomedullary locked nail. INTERVENTION: Reamed, trochanteric insertion of an
      intramedullary nail with proximal locking screws placed in a cephalomedullary
      direction. MAIN OUTCOME MEASUREMENT: Patient and injury data, radiographic
      analyses, and complications of treatment were assessed at a minimum of 12 months.
      RESULTS: Sixty-one of 87 patients (70%) were available at a mean of 19.8 months
      (range, 12-44 months). Sixty of 61 fractures united after the index procedure.
      Complications included one delayed union successfully treated with exchange
      nailing, one distal locking screw fracture (allowing dynamization and completion
      of fracture healing), two patients with postoperative deformity that required a
      derotation procedure, and two drill bits that broke intraoperatively and were
      retained. There were no major complications at the hip, no migration or failure
      of proximal locking screws, and no screws required removal. CONCLUSIONS: Using a
      reconstruction nail and cephalomedullary proximal locking screws for antegrade
      femoral nailing of femoral shaft fractures was not associated with major
      complications in this series. This modification of standard femoral nailing
      offers potential advantages, including fixation of any "missed" associated
      femoral neck fractures and prevention of late hip fractures that might occur
      above the nail.

PMID- 21076247
TI  - Does stress-induced hyperglycemia increase the risk of perioperative infectious
      complications in orthopaedic trauma patients?
AB  - OBJECTIVE: To determine if hyperglycemia in postoperative orthopaedic trauma
      patients with no known history of diabetes mellitus is associated with an
      increased rate of infectious complications. DESIGN: Retrospective review.
      SETTING: University Level I trauma center. PATIENTS: One hundred ten consecutive
      orthopaedic trauma patients, MAIN OUTCOME MEASUREMENTS: Perioperative pneumonia,
      urinary tract infection, sepsis, or wound infection. METHODS: Patients were
      divided into two subgroups based on mean serum glucose greater than 220 mg/dL
      (hyperglycemic index [HGI] 3.0 or greater). The incidence of infections was
      calculated for the following factors: age, medical comorbidities, Injury Severity
      Score, body mass index, HGI, sex, transfusions, tobacco use, and presence of open
      fracture. Means were compared using two-sample t tests (with or without
      adjustment for unequal variances as necessary), and percentages were compared
      using either chi square or Fisher exact tests. If the data were not normally
      distributed or measured on the ordinal scale, then the Wilcoxon rank sum test was
      used. A multivariate analysis using logistic regression was performed with the
      presence or absence of an infection as the dependent variable. A two-tailed P
      value < 0.05 was considered significant. SAS, Version 9.1 (SAS Institute Inc,
      Cary, NC), was used for all analyses. RESULTS: Forty-six infections occurred in
      28 patients, including 11 wound infections, 17 pneumonia, 11 urinary tract
      infections, and seven sepsis or bacteremia. The overall infection rate for the
      study cohort was 28 of 110 (25%). No significant associations were identified
      among age, comorbidities, transfusions, tobacco use, open fracture, sex, body
      mass index, Injury Severity Score, and the presence of any infection. Ninety nine
      patients had an HGI less than 3.0 and 21 (21%) of these had a perioperative
      infection. Eleven patients had an HGI 3.0 or greater and seven (64%) of these had
      a perioperative infection. This difference was significant (P = 0.0056).
      CONCLUSIONS: Mean perioperative glucose levels greater than 220 mg/dL (HGI
      greater than 3.0) were associated with a seven times higher risk of infection in
      orthopaedic trauma patients with no known history of diabetes mellitus. Further
      prospective studies are needed to study the effects of stress-induced
      hyperglycemia and to determine whether this physiological response is protective
      or detrimental to the postoperative trauma patient.

PMID- 21076248
TI  - The results of early primary open reduction and internal fixation for treatment
      of OTA 43.C-type tibial pilon fractures: a cohort study.
AB  - OBJECTIVES: The optimal treatment for pilon fractures remains controversial. We
      have used early single-stage open reduction and internal fixation (ORIF) to treat
      these injuries and the purpose of this study was to determine the safety and
      efficacy of this strategy. DESIGN: Cohort study. SETTING: Level I trauma center.
      PATIENTS/PARTICIPANTS: Ninety-five patients with Orthopaedic Trauma Association
      type 43.C pilon fractures. INTERVENTION: Primary ORIF. MAIN OUTCOME MEASUREMENT:
      Primary: Wound dehiscence or deep infection requiring surgery; secondary: quality
      of fracture reduction, functional outcomes (SF-36 and Foot and Ankle Outcome
      Score). RESULTS: Primary ORIF was performed within 24 hours in 70% of cases and
      within 48 hours in 88%. Reduction was judged to be anatomic in 90% cases. Six
      patients developed a deep wound infection or dehiscence that required surgical
      debridement, four after open fractures (four of 21 [19%]) and two after closed
      fractures (two of 74 [2.7%]). Complications were associated with local scarring,
      chronic alcohol abuse, schizophrenia, diabetes, and peripheral neuropathy.
      CONCLUSIONS: Provided surgery is performed expeditiously by experienced
      orthopaedic trauma surgeons, most tibial pilon fractures can be stabilized by
      primary ORIF within a safe and effective operative window with relatively low
      rates of wound complications, a high quality of reduction, and functional
      outcomes that compare favorably with the published results for all other reported
      surgical treatments of these severe injuries.

PMID- 21076250
TI  - Stabilization of displaced articular fragments in calcaneal fractures using
      bioabsorbable pin fixation: a technique guide.
AB  - Successful operative intervention in displaced intra-articular calcaneal
      fractures depends in part on the maintenance of an anatomic reduction of the
      posterior facet. This guide describes our use of bioabsorbable implants to solve
      this problem.

PMID- 21076249
TI  - Objective CT-based metrics of articular fracture severity to assess risk for
      posttraumatic osteoarthritis.
AB  - OBJECTIVES: Intra-articular fractures predispose patients to posttraumatic
      osteoarthritis (PTOA) with associated chronic joint pain and decreased function.
      The success of articular fracture management is dependent on how the fracture is
      treated and on fracture type and severity. The purpose of the present study was
      to correlate objective computed tomography (CT)-based indices of intra-articular
      fracture severity with subsequent joint degeneration. It was hypothesized that an
      injury severity metric that included objective measures of articular disruption,
      of fracture energy, and of fragment displacement/dispersal would be a useful
      predictor of PTOA. METHODS: Novel CT-based image analysis techniques were used to
      quantify acute injury characteristics in a prospective series of 20 tibial
      plafond fractures managed by articulated external fixation with later definitive
      surgical fracture reduction performed after soft tissue swelling had sufficiently
      resolved. PTOA severity was assessed 2 years postinjury using the Kellgren
      Lawrence radiographic grading scale. A predictive model was developed by linearly
      regressing these 2-year Kellgren-Lawrence outcomes on the CT-based severity
      metrics. RESULTS: A combined acute severity score involving articular disruption
      and fracture energy successfully predicted PTOA severity (R2 = 0.70), whereas
      fragment displacement/dispersal and surgeon opinion correlated much less well
      with degeneration (R = 0.42 and 0.47). The concordance between the combined
      metric and PTOA severity was 88%. CONCLUSIONS: The findings of this study
      indicate that objective CT-based metrics of acute injury severity can reliably
      predict intermediate-term PTOA outcomes in this challenging class of articular
      fractures. Quantitative biomechanical assessment of injury characteristics
      provides new possibilities to improve fracture management and to guide PTOA
      research.

PMID- 21076253
TI  - Context for WOC practice: urban myths and the randomized controlled trial.

PMID- 21076254
TI  - 2010 WOCN Society's President's Award recipient--Janice C. Colwell.

PMID- 21076255
TI  - 2010 JWOCN Manuscript Award winners.

PMID- 21076257
TI  - Management of the patient with a fecal ostomy: best practice guideline for
      clinicians.

PMID- 21076258
TI  - Wound care in diabetic patients.

PMID- 21076260
TI  - Measurement and instrument design.
AB  - The soundness and robustness of research depend on the quality of data
      collection. An overview of the important considerations when developing an
      instrument for data collection is presented in this article. These considerations
      include theoretical issues fundamental to instrument development, conceptual
      model development, selection of instrument types, questionnaire design and
      construction, and establishment of reliability and validity.

PMID- 21076261
TI  - Factors associated with pressure ulcers in patients in a surgical intensive care
      unit.
AB  - PURPOSE: We sought to describe the occurrence of pressure ulcers in patients
      managed in a surgical intensive care unit (ICU) and report preliminary work
      toward development of a pressure ulcer risk assessment tool for use in this
      population that incorporates comorbidities and other factors not addressed in
      previous instruments. SUBJECTS AND SETTINGS: Three hundred sixty-nine patients
      managed in the surgical ICU at Yale-New Haven Hospital comprised the sample.
      METHODS: Demographic and clinical data, including Braden Scale scores, were
      collected in this prospective, 2-phase study. The principal investigator (G.C.S.)
      performed skin assessments on all patients. We used chi-square analysis and t
      tests to determine variables to include in a stepwise logistic regression
      analysis to determine factors independently associated with the development of
      pressure ulcers. INSTRUMENT: We collected data, using a form we developed that
      contained demographic and clinical factors found in previous research and in our
      clinical practice to be associated with pressure ulcers. RESULTS: Eighty-eight
      out of 369 patients (23.9%) experienced a hospital-acquired pressure ulcer.
      Braden Scale scores ranged from 6 to 21, with a mean score of 11.9 +/- 2.2. A
      lower Braden Scale score, the presence of diabetes mellitus, and patient age 70
      years or older independently predicted the development of a pressure ulcer. These
      factors have been incorporated into the preliminary Surgical ICU Pressure Ulcer
      Risk Assessment scale. CONCLUSIONS: Findings from this study suggest that, in
      addition to a low Braden Scale score, age >70 years and a diagnosis of diabetes
      may represent clinically relevant pressure ulcer risk factors in the surgical
      intensive care population and that patients with these factors may benefit from
      more aggressive preventive care. In addition, the Surgical ICU Pressure Ulcer
      Risk Assessment scale requires additional psychometric testing before its use can
      be recommended for the research or practice settings.

PMID- 21076262
TI  - Bibliometric analysis of pressure ulcer research: 1990-2009.
AB  - PURPOSE: Bibliometric evaluation provides a method for evaluating trends in
      publications related to a specific topic. This search focused on pressure ulcer
      (PU) care; journals and authors with the greatest contribution and impact were
      emphasized. DESIGN: Bibliometric evaluation. METHODS: Data encompassing the
      period from 1990 to 2009 were extracted from the Science Citation Index online
      version. We analyzed selected documents with "pressure ulcer" as a part of the
      title, abstract, or key words and reported the following parameters: trends of
      publication output, document types, subject category, journal pattern,
      authorship, and research in nursing disciplines. RESULTS: The annual number of
      articles on PUs grew at a rapid rate, from approximately 39 in 1991 to 259 in
      2009. The main subject categories in which research on PUs was conducted were
      surgery and nursing, each of which accounted for more than 10% of total articles.
      The United States was the dominant country in terms of volume of articles. The
      relationship between nurse staffing and PU-related outcomes is currently the
      major focus of PU nursing research, followed by risk assessment scale
      evaluations. CONCLUSION: We found that the number of PU-related publications has
      grown at a rapid rate over the past 20 years, reflecting an increasing awareness
      of the importance of PU prevention and management.

PMID- 21076263
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: an ongoing
      challenge for WOC nursing.
AB  - Infection is a common complication of chronic wounds that delays healing.
      Community-acquired methicillin-resistant Staphylococcus aureus has emerged as a
      common pathogen and major impediment to healing affected chronic wounds.
      Community-acquired methicillin-resistant S aureus is virulent, highly
      communicable, and difficult to eradicate. Treatment options include incision and
      drainage, debridement, and systemic antimicrobials. Early aggressive wound
      management and appropriate antibiotic therapy are considered essential to
      successful treatment. Facility-specific protocols should be developed to minimize
      the spread of this organism to the general population, with particular attention
      focused on protecting patients burdened with chronic wounds. This article reviews
      current knowledge of community-acquired methicillin-resistant S aureus, focusing
      on its impact on persons with chronic wounds.

PMID- 21076264
TI  - Palliative wound care: a concept analysis.
AB  - The concept of palliative wound care is in its infancy, with relevant literature
      emerging in the 1980s. Palliative wound care has evolved over time as new
      research and practice initiatives continue to explore its usefulness. We applied
      Rodgers' evolutionary concept analysis to a conceptual exploration of palliative
      wound care. The findings of this analysis identified reoccurring themes that were
      grouped into the concept's antecedents, attributes, and consequences. We found
      that palliative wound care is a holistic integrated approach to care that
      addresses symptom management and psychosocial well-being, is multidisciplinary,
      is driven by patient/family goals, and is integrated into wound healing
      principles and everyday practice. The integration of palliative wound care into
      the continuum of wound care, not just at the end of life, is the logical
      conclusion.

PMID- 21076266
TI  - High volume output from a jejunostomy.

PMID- 21076267
TI  - Diet and eating pattern modifications used by community-living adults to manage
      their fecal incontinence.
AB  - PURPOSE: The study aimed to describe modifications in diet and eating patterns
      made by community-living people to manage fecal incontinence (FI), and to compare
      these differences according to sex, age, and FI severity. SUBJECTS AND SETTINGS:
      Subjects were 188 community-living adults (77% female, 92% white, 34% aged 65
      years or older) in the upper Midwest who participated in a study about managing
      FI with dietary fiber. METHODS: Subjects were interviewed about diet and eating
      pattern changes that they made to manage FI, and self-reported demographic data.
      FI severity was recorded daily. RESULTS: Fifty-five percent of participants
      perceived that some foods worsen their FI (eg, fatty or spicy foods and dairy
      products). More women than men (40% vs 18%, P = .008) reported avoiding foods to
      manage FI. A greater percentage of younger than older people believed that
      fatty/greasy foods (15% vs 4%) and alcohol (14% vs 3%) worsened their FI.
      Subjects with a higher FI severity score appeared to wait until FI was more
      severe before restricting caffeine than those with lower severity scores (22.2 +/
      9.8 vs 11.69 +/- 8.3, P = .034). One-third of subjects consumed foods rich in
      dietary fiber to prevent FI. Subjects also reported altered eating or cooking
      patterns, skipping meals, or eating at consistent times to manage FI.
      CONCLUSIONS: Diet modification for managing FI incorporates restriction of some
      foods, along with adding others foods to the diet. Nursing assessments of self
      care practices for FI should include diet and eating pattern changes when
      developing a plan of care.

PMID- 21076268
TI  - Continence certification.

PMID- 21076269
TI  - Techniques for preventing and managing tube-related complications.
AB  - BACKGROUND: The management of jejunostomy and gastrostomy tubes that are not well
      stabilized and leak effluent around the insertion site present significant
      challenges to WOC nursing practice. The result is often peritubular skin erosion,
      patient discomfort, and high-volume fluid losses that are not measurable. CASE:
      WOC nursing was consulted when a 70-year-old woman with a jejunostomy tube
      experienced leakage, skin erosion, and pain. A novel technique for tube
      stabilization and local treatment of the peritubular skin was successful in
      stabilizing her jejunostomy tube, protecting the skin surrounding the tube,
      relieving associated pain, and enabling accurate measurement of output from the
      tube. Alternative strategies for stabilization and treatment are discussed.
      CONCLUSION: The outcomes of patients who have been treated with these strategies
      has been improved comfort since they do not feel any tube movement and decreased
      pain since the skin is protected from the caustic effluent and remains healthy
      and intact.

PMID- 21076271
TI  - Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co
      infected patients with advanced immunosuppression.
AB  - OBJECTIVE: to determine if intrahepatic immune activation is increased in HIV
      hepatitis B virus (HBV) co-infected patients compared to HBV mono-infected
      patients and whether this reduced following HBV-active antiretroviral therapy
      (ART) in HIV-HBV co-infected patients. DESIGN: : Case-control observational
      study. METHODS: we examined liver biopsies for markers of T-cell and monocyte
      infiltration and activation, natural killer cells, hepatic stellate cell (HSC)
      activation (staining for alpha smooth muscle actin) and apoptosis [using terminal
      dUTP nick-end labelling (TUNEL)] in treatment-naive Asian HIV-HBV co-infected (n
      = 16) and HBV mono-infected patients matched for age and HBV e-antigen status (n
      = 16). Liver biopsies from a subset of co-infected patients (n = 15) were also
      compared prior to and following 48 weeks of HBV-active ART. RESULTS: HIV-HBV co
      infected patients had a median CD4 T-cell count of 25 cells/microl and lower
      alanine aminotransferase levels than HBV mono-infected patients (P = 0.03). In
      HIV-HBV co-infected patients, hepatocyte apoptosis was increased (P = 0.04) but
      there were fewer intrahepatic CD4 and CD8 T cells (P < 0.001), lower activation
      of intrahepatic T cells, Kupffer cells and HSC (P = 0.002, 0.008 and < 0.001,
      respectively). Following ART, there was a significant decrease in intrahepatic
      HBsAg staining (P = 0.04) and Kupffer cell activation (P = 0.003). CONCLUSIONS:
      we found no evidence of increased intrahepatic mononuclear and HSC activation in
      this cohort of HIV-HBV co-infected individuals with advanced immune suppression.
      An increase in intra-hepatic apoptosis in HIV-HBV co-infected individuals may
      potentially contribute to accelerated fibrosis in this setting.

PMID- 21076272
TI  - Empirical evaluation of the need for 'on-going consent' in clinical research.
AB  - OBJECTIVE: Some commentators argue that informed consent for clinical research
      should be an on-going process, which begins, rather than ends, with participants'
      initial consent. Lacking, however, are empirical data on whether there is a need
      for 'on-going consent'. DESIGN: Two self-administered surveys - a baseline survey
      at initial consent and a follow-up survey 2-3 years later - to assess whether
      participants remain informed over time. METHODS: Respondents were adults with HIV
      disease from Argentina, Brazil and Thailand enrolled in a long-term clinical
      trial. RESULTS: Respondents overall were well informed at baseline. At follow-up,
      many reported being not informed about aspects of the study central to their on
      going participation. With respect to the possibility of withdrawal, 38.5% of
      respondents at follow-up reported being 'not at all' informed. At follow-up,
      71.1% wanted more information. Yet, 62.8% had not asked any questions during the
      entire study. Reasons for not asking questions included not having an opportunity
      (16.4%) and not knowing whom to ask (15.5%). CONCLUSIONS: The standard consent
      process resulted in participants being well informed at enrollment. Yet, this
      process was not sufficient to keep them informed about aspects of the study
      central to their on-going participation. In addition, participants who wanted
      more information often did not ask for it. These findings provide empirical
      support for recommendations that clinical trials should consider including a
      process of 'on-going consent'.

PMID- 21076273
TI  - Comprehensive analysis of virus-specific T-cells provides clues for the failure
      of therapeutic immunization with ALVAC-HIV vaccine.
AB  - BACKGROUND: HIV-specific T-cell-based vaccines have been extensively studied in
      both prevention and therapeutic settings, with most studies failing to show
      benefit, and some suggesting harm. We previously performed a multicenter, double
      blind, placebo-controlled phase II clinical trial in which 65 antiretroviral
      treated patients were randomized to receive an HIV-1 recombinant canarypox
      vaccine (vCP1452) or placebo, followed by analytical treatment interruption.
      Patients exposed to vaccine had higher levels of viral replication and more rapid
      time to treatment resumption. OBJECTIVE: In the present study we report the
      results from extensive immunological investigations to test whether the
      preferential expansion of HIV-specific CD4(+), rather than CD8(+) T cells, could
      account for these unexpected results. METHODS: Polychromatic flow cytometry was
      used to characterize the functional and phenotypic profile of antigen-specific
      CD8(+) and CD4(+) T cells induced by the immunization. RESULTS: We found a
      significant increase in HIV-specific CD4(+) T cells producing IFN-gamma and IL-2
      in the 4 injections arm compared to the placebo arm following vaccination. In
      contrast, no difference was observed following vaccination in the phenotype and
      functional capacity within the CD8(+) T-cell compartment. Neither HLA biases, nor
      immune hyper-activation, or Env-specific facilitating antibodies were associated
      with the enhanced virus rebound observed in vaccinees. CONCLUSION: Our data
      suggest that a vaccine-induced transient activation of HIV-specific CD4(+) but
      not CD8(+) T cells may have a detrimental effect on HIV outcomes. These findings
      may provide a mechanistic basis for higher rates of HIV acquisition or
      replication that have been associated with some T-cell vaccines.

PMID- 21076274
TI  - Clinical and virological outcomes in HIV-infected patients with chronic hepatitis
      B on long-term nucleos(t)ide analogues.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection is common in HIV-positive
      individuals and increases liver-related mortality. Nucleos(t)ide analogues with
      activity against both HBV and HIV are widely used in coinfected patients, but its
      long-term effect on liver disease is unknown. METHODS: Clinical outcomes, HBsAg
      and/or HBeAg clearance, and changes in liver stiffness were longitudinally
      evaluated retrospectively in all HIV-HBV-coinfected individuals followed at our
      institution. RESULTS: A total of 92 patients with HIV-HBV coinfection were
      identified, 19 of them superinfected with hepatitis delta virus. Their median
      time of follow-up was 35 months. Overall, 94% received lamivudine/emtricitabine
      and 82% tenofovir. Serum HBV-DNA was undetectable in 89%. Seven patients cleared
      serum HBsAg (2.6/100 patient-years), in four of them accompanied with anti-HBs
      seroconversion. Of note, two of them had hepatitis delta. Another 11 out of 42
      HBeAg-positive patients cleared HBeAg (9/100 patient-years) and five of them
      experienced anti-HBe seroconversion. Liver decompensation and death occurred in
      eight (2.9/100 patient-years) and six (2.2/100 patient-years), respectively.At
      baseline, liver fibrosis was defined as null-mild (48%), moderate-advanced (28%)
      or cirrhosis (24%). At last visit, after a median of 40 months in 71 patients,
      75% showed no changes, whereas improvement was recognized in 17% and worsening in
      8%. CONCLUSION: Most HIV-HBV-coinfected patients treated with anti-HBV active
      nucleos(t)ide analogues experience an amelioration of liver fibrosis progression,
      with low rates of hepatic decompensation and death. Serum HBeAg or HBsAg
      seroconversion occurs at yearly rates of 9 and 2.6%, respectively, even in
      patients with delta hepatitis.

PMID- 21076275
TI  - Prospective study of renal function in HIV-infected pediatric patients receiving
      tenofovir-containing HAART regimens.
AB  - AIM: to describe the impact of tenofovir disoproxil fumarate (TDF) use on renal
      function in HIV-infected pediatric patients. DESIGN: it is a prospective,
      multicenter study. The setting consisted of five third-level pediatric hospitals
      in Spain. The study was conducted on patients aged 18 years and younger who had
      received TDF for at least 6 months. The intervention was based on the study of
      renal function parameters by urine and serum analyses. The main outcome measures
      were renal function results following at least 6 months of TDF therapy. RESULTS:
      forty patients were included (32 were white and 26 were diagnosed with AIDS).
      Median (range) duration of TDF treatment was 77 months (16-143). There were no
      significant changes in the estimated creatinine clearance. Urine osmolality was
      abnormal in eight of 37 patients, a decrease in tubular phosphate absorption was
      documented in 28 of 38 patients, and 33 of 37 patients had proteinuria. A
      statistically significant decrease in serum phosphate and potassium
      concentrations was observed during treatment (P = 0.005 and P = 0.003,
      respectively), as well as a significant relationship between final phosphate
      concentration and tubular phosphate absorption (P = 0.010). A negative
      correlation was found between phosphate concentration and time on TDF.
      CONCLUSIONS: TDF use showed a significant association with renal tubular
      dysfunction in HIV-infected pediatric patients. Periodic assessment of tubular
      function may be advisable in the follow-up of this population.

PMID- 21076276
TI  - Progression and regression of premalignant cervical lesions in HIV-infected women
      from Soweto: a prospective cohort.
AB  - OBJECTIVE: To ascertain progression and regression of cervical dysplasia in HIV
      infected women in Soweto. DESIGN: Prospective cohort. METHODS: Women attending an
      HIV wellness clinic were offered cervical smears as part of care; smears were
      assessed using the Bethesda system. Those with high-grade lesions or worse were
      referred for colposcopy. Progression analyses included women with at least two
      smears at least 5.5 months apart. Hazard ratios were used to ascertain predictors
      of progression. RESULTS: Two thousand, three hundred and twenty-five women had a
      baseline smear; their median age and CD4 cell count was 32 years and 312
      cells/MUl, respectively; 17% were taking highly active antiretroviral therapy
      (HAART); 62, 20 and 14% had normal, low-grade squamous intraepithelial lesions
      (LSIL) or high-grade squamous intraepithelial lesions (HSIL), respectively. Of
      those with baseline normal or LSIL smears, 1074 had another smear; progression
      from normal to LSIL was 9.6/100 person-years (95% CI 8.3-11.1) and progression
      from normal or LSIL to HSIL was 4.6/100 person-years (95% CI 3.9-5.5). Of 225
      women with LSIL at baseline and at least one subsequent smear at least 11.5
      months later, 44.0% regressed to normal (21.2/100 person-years (95% CI 17.5
      25.7)). Multivariate models suggested increasing risk for progression in women
      with CD4 cell count below 500 cells/MUl and HAART may reduce the risk of
      progression [adjusted hazard ratio (aHR) 0.72 (0.52-0.99)]. CONCLUSION: HIV
      infected women have high rates of prevalent and incident HSIL and LSIL with
      relatively low risk of regression to normal from LSIL. HAART appears to protect
      against progression. Our findings suggest cervical screening intervals should be
      less than 10 years - irrespective of age in women with CD4 cell counts below 500
      cells/MUl.

PMID- 21076279
TI  - Fondaparinux cross-reacts with heparin antibodies in vitro in a patient with
      fondaparinux-related thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) related to fondaparinux has been rarely
      reported, although the ability of fondaparinux to cross-react with heparin
      antibodies has been often a subject of debate. A patient previously exposed to
      unfractionated heparin and low-molecular-weight heparin (LMWH) was diagnosed with
      HIT. During treatment with fondaparinux for 5 consecutive days, his
      thrombocytopenia significantly deteriorated. A functional platelet activation
      test in vitro showed clear platelet activation after serum exposure with
      fondaparinux. After discontinuation of fondaparinux, the platelet count was
      rapidly reestablished. Fondaparinux cross-reacted with heparin antibodies in this
      case of HIT, resulting in a deterioration of thrombocytopenia. The implication of
      this drug in HIT was observed clinically and demonstrated in vitro using a
      platelet activation test.

PMID- 21076278
TI  - A randomized crossover study to compare efavirenz and etravirine treatment.
AB  - BACKGROUND: Efavirenz (EFV) causes neuropsychiatric side-effects and an
      unfavourable blood lipid profile. We investigated the effect of replacing EFV
      with etravirine (ETR) on patient preference, sleep, anxiety and lipid levels.
      METHOD: Study participants did not complain of side-effects, had tolerated EFV
      for at least 3 months, with less than 50 copies/ml HIV-RNA. After randomization,
      the ETR-first group started with ETR (400 mg daily) [DOSAGE ERROR CORRECTED] with
      EFV-placebo and the EFV-first group with EFV with ETR-placebo. After 6 weeks,
      both groups switched to the alternate regimen. Nucleoside reverse transcriptase
      inhibitors were continued without any change. The primary end point was patient
      preference for the first or the second regimen, assessed after 12 weeks. RESULTS:
      Fifty-eight patients were enrolled with a median CD4 cell count of 589 cells/MUl
      and the duration of previous EFV therapy was 3.9 years. Fifty-five patients
      completed the study. When asked about treatment preference after 12 weeks, 16
      preferred EFV and 22 preferred ETR, whereas 17 did not express a preference (P =
      NS). Patients who continued EFV during the first phase of the trial preferred EFV
      (15/21, 71%), whereas patients who started with ETR were more likely to prefer
      ETR (n = 16/17, 94%). This order effect was strongly significant (P < 0.0001).
      Quality of sleep, depression, anxiety and stress scores did not differ
      significantly between groups. Median plasma cholesterol levels decreased by 0.7
      mmol (29 mg/100 ml) after replacing EFV with ETR (P < 0.002). CONCLUSION: After
      substitution of EFV by ETR, patients did not express a significant preference for
      ETR. There was no measurable effect on neuropsychiatric symptoms and sleep.
      Cholesterol decreased.

PMID- 21076280
TI  - A patient with 'spontaneous' heparin-induced thrombocytopenia and thrombosis
      after undergoing knee replacement.
AB  - Exogenous heparin exposure is the major risk factor for heparin-induced
      thrombocytopenia and thrombosis (HITT). To date, only five cases of 'spontaneous'
      HITT have been reported in the literature. We report the case of a 60-year-old
      man who developed severe thrombocytopenia (15 000/MUl) and bilateral deep venous
      thromboses 10 days after bilateral knee replacement. There was no evidence of
      heparin exposure upon review of the patient's preoperative and postoperative
      medication history. Heparin: platelet factor-4 (PF4) antibodies were positive as
      was the serotonin release assay. Anticoagulation with argatroban along with
      prednisone and intravenous immune globulin were administered. Anticoagulation
      with argatroban was bridged to warfarin once his platelet count reached 100
      000/MUl, and he was continued on oral prednisone taper. Heparin: PF4 antibodies
      were negative 3 months after the event. Six months later, Doppler ultrasound
      revealed deep vein thrombosis. This case represents a third 'spontaneous' episode
      of HITT in the context of knee replacement surgery without heparin
      administration. It is unclear whether these cases are a result of exposure to a
      heparin-like proteoglycan such as chondroitin sulfate during surgery that binds
      PF4, or whether the perioperative pro-inflammatory milieu is the inciting event.
      Further consideration of precipitating events in these individuals merits further
      investigation and may lead to valuable insight into the pathophysiology of
      heparin-independent PF4-related thrombocytopenia and thrombosis.

PMID- 21076281
TI  - Perioperative bridging therapy with low molecular weight heparin for patients
      with inherited thrombophilia and antiphospholipid syndrome on long-term
      acenokumarol therapy.
AB  - The aim of the study is to present our own perioperative bridging therapy with
      low molecular weight heparin (LMWH) for surgical patients with thrombophilia on
      long-term acenokumarol therapy [oral anticoagulant (OAC)]. In some European
      countries, the drug used in secondary antithrombotic prophylaxis is acenokumarol.
      Forty-two patients with inherited thrombophilia and 21 with antiphospholipid
      syndrome underwent surgery. All patients were on long-term OAC. This OAC was
      interrupted 2 days before elective surgery and since that day half of the
      individual therapeutic dose of LMWH was administered. On day of surgery, the LMWH
      therapeutic dose was divided into two parts. Starting with day 2 after surgery,
      the patient was again given half of the individual dose of LMWH every 24 h. On
      day 4, OAC was additionally included. Both drugs were administered until
      stabilization of international normalized ratio (INR) values within the
      therapeutic target for 2 consecutive days. LMWH was then interrupted, whereas OAC
      continued. No symptoms or episodes of venous thromboembolism were observed. No
      intraoperative or postoperative hemorrhagic complications were reported. The
      results suggest that our perioperative bridging therapy is safe and effective for
      prevention of thromboembolic and hemorrhagic complications.

PMID- 21076282
TI  - Learning from within to ensure a successful implementation of an electronic
      health record.
AB  - Implementation of an electronic health record has multiple facility-wide
      challenges affecting all direct care providers. Because the dialysis unit and
      emergency department had already undergone transition with differing electronic
      systems several years before, could anything be learned from these past
      experiences to inform the future institution-wide implementation? Utilizing focus
      groups and surveys, recurring themes emerged: "It will take one hundred charts";
      allowing for "self-discovery" of individual learning progression; establishing
      and communicating "clear processes" for use of the electronic record; and
      ensuring adequate support to facilitate a "customer-focused" approach in learning
      how to utilize electronic documentation. Although training related to the
      electronic health record was discussed in all focus groups, training was not
      described as a main concern, which challenged our initial presumptions that
      education was the key resource for a successful change. Three of the four themes
      uncovered in this study are not unique and corroborate the findings in other
      studies. "Clear processes" is a new theme not previously identified. These themes
      with recommendations were presented to the electronic health record design team
      to assist with the hospital-wide implementation.

PMID- 21076277
TI  - Editorial neuroAIDS review.

PMID- 21076283
TI  - Use of a computer-mediated Delphi process to validate a mass casualty conceptual
      model.
AB  - Since the original work on the Delphi technique, multiple versions have been
      developed and used in research and industry; however, very little empirical
      research has been conducted that evaluates the efficacy of using online computer,
      Internet, and e-mail applications to facilitate a Delphi method that can be used
      to validate theoretical models. The purpose of this research was to develop
      computer, Internet, and e-mail applications to facilitate a modified Delphi
      technique through which experts provide validation for a proposed conceptual
      model that describes the information needs for a mass-casualty continuum of care.
      Extant literature and existing theoretical models provided the basis for model
      development. Two rounds of the Delphi process were needed to satisfy the criteria
      for consensus and/or stability related to the constructs, relationships, and
      indicators in the model. The majority of experts rated the online processes
      favorably (mean of 6.1 on a seven-point scale). Using online Internet and
      computer applications to facilitate a modified Delphi process offers much promise
      for future research involving model building or validation. The online Delphi
      process provided an effective methodology for identifying and describing the
      complex series of events and contextual factors that influence the way we respond
      to disasters.

PMID- 21076284
TI  - Factors associated with nurses' informatics competency.
AB  - Informatics competency has become an essential requirement for nurses to fulfill
      their professional roles. This study examined the factors affecting informatics
      competency to help develop strategies to improve nurses' informatics practice. A
      cross-sectional survey was conducted in two tertiary teaching hospitals in Seoul,
      Korea. A questionnaire was designed to collect data on nurses' informatics
      competency, basic computer skills, attitudes toward computerization, and general
      characteristics. The response rate was 96.4% (350/363). Multiple regression
      analysis was performed to determine the characteristics affecting informatics
      competency. More than two-thirds of the nurses (69.2%) considered their overall
      informatics competency to be below average. They scored the highest on the
      informatics topics of security and confidentiality, and the lowest on telehealth.
      More than half (58.9%) rated their computer skills to be below average. Nurses
      had favorable attitudes toward computerization. Significant factors associated
      with informatics competency were basic computer skills and formal informatics
      education. The study findings suggest that the enhancement of basic computer
      skills and incorporation of informatics into formal nursing curricula are needed
      to improve the nurses' competency in managing and using healthcare information.

PMID- 21076285
TI  - Effect of socioemotional stress on the quality of cardiopulmonary resuscitation
      during advanced life support in a randomized manikin study.
AB  - OBJECTIVE: The aim of this study was to evaluate whether socioemotional stress
      affects the quality of cardiopulmonary resuscitation during advanced life support
      in a simulated manikin model. DESIGN: A randomized crossover trial with advanced
      life support performed in two different conditions, with and without exposure to
      socioemotional stress. SETTING: The study was conducted at the Stavanger Acute
      Medicine Foundation for Education and Research simulation center, Stavanger,
      Norway. SUBJECTS: Paramedic teams, each consisting of two paramedics and one
      assistant, employed at Stavanger University Hospital, Stavanger, Norway.
      INTERVENTIONS: A total of 19 paramedic teams performed advanced life support
      twice in a randomized fashion, one control condition without socioemotional
      stress and one experimental condition with exposure to socioemotional stress. The
      socioemotional stress consisted of an upset friend of the simulated patient who
      was a physician, spoke a foreign language, was unfamiliar with current Norwegian
      resuscitation guidelines, supplied irrelevant clinical information, and
      repeatedly made doubts about the paramedics' resuscitation efforts. Aural
      distractions were supplied by television and cell telephone. MEASUREMENTS AND
      MAIN RESULTS: The primary outcome was the quality of cardiopulmonary
      resuscitation: chest compression depth, chest compression rate, time without
      chest compressions (no-flow ratio), and ventilation rate after endotracheal
      intubation. As a secondary outcome, the socioemotional stress impact was
      evaluated through the paramedics' subjective workload, frustration, and feeling
      of realism. There were no significant differences in chest compression depth (39
      vs. 38 mm, p = .214), compression rate (113 vs. 116 min-1, p = .065), no-flow
      ratio (0.15 vs. 0.15, p = .618), or ventilation rate (8.2 vs. 7.7 min-1, p =
      .120) between the two conditions. There was a significant increase in the
      subjective workload, frustration, and feeling of realism when the paramedics were
      exposed to socioemotional stress. CONCLUSION: In this advanced life support
      manikin study, the presence of socioemotional stress increased the subjective
      workload, frustration, and feeling of realism, without affecting the quality of
      cardiopulmonary resuscitation.

PMID- 21076287
TI  - Persistent low microcirculatory vessel density in nonsurvivors of sepsis in
      pediatric intensive care.
AB  - OBJECTIVE: To investigate the time course and predictive value of microvascular
      alterations in children with severe sepsis. DESIGN: Single-center, prospective
      observational study. SETTING: Intensive care unit of a level III university
      children's hospital. PATIENTS: Patients with septic shock, requiring the
      administration of fluid and vasopressor agents and/or inotropes after the
      correction of hypovolemia, who were intubated and ventilated, were included.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculation was
      assessed in the buccal mucosa, using orthogonal polarization spectral imaging,
      within 24 hrs after admission. Subsequent measurements were performed every 24
      hrs for 3 days. The measurements were discontinued when the patient was
      extubated. There were no significant differences in the functional capillary
      density or microvascular flow index for all vessel types between survivors and
      nonsurvivors on day 1. In the survival group, the functional capillary density
      increased significantly between day 1 and day 2 from 1.7 cm/cm (0.8-3.4) to 4.3
      cm/cm (2.1-6.9) (p = .001). Functional capillary density values in nonsurvivors
      did not change (day 1: 3.2 cm/cm [0.8-3.8]; day 2: 1.9 cm/cm [1.0-2.1]). The
      median functional capillary density on days 2 and 3 were significantly lower in
      nonsurvivors (day 2: 1.9 cm/cm [1.0 -2.1] vs. 4.3 cm/cm [2.1-6.9], p = .009; day
      3: 1.8 cm/cm [1.0-2.0] vs. 4.7 cm/cm [2.1-8.6], p = .01). The microvascular flow
      index for all vessel types improved in survivors and did not change in
      nonsurvivors. Differences in microvascular flow index values between survivors
      and nonsurvivors were not significant. CONCLUSION: Persistent microcirculatory
      alterations can be prognostic for survival in children with septic shock.

PMID- 21076288
TI  - Cardiovascular implantable electrophysiological device-related infections: a
      review.
AB  - PURPOSE OF REVIEW: The use of cardiac implantable electrophysiological device
      (CIED) therapy in the management of cardiac disease is increasing with the
      improvements in technology of permanent pacemaker and implantable cardioverter
      defibrillators. Accordingly CIED-related infections are increasing and have
      become an important clinical problem. The purpose of this review is to summarize
      current literature on the epidemiology, risk factors, pathophysiology, diagnosis
      and management of CIED-related infections. RECENT FINDINGS: The diagnosis and
      management of CIED-related infections can be difficult. Recent research would
      suggest extraction of all CIED components, and concomitant appropriate antibiotic
      therapy is the principal management modality of CIED component and pocket
      infection. The exact duration of antibiotic therapy and timing of re-implantation
      still require further delineation in the absence of comparative evidence;
      however, improvements in technologies such as the excimer laser have enabled
      percutaneous extraction to be performed effectively and safely in the vast
      majority of patients. Differentiating CIED-related infection from noninfected
      mechanical issues that may not require extraction or antibiotics can be very
      difficult. Research is continuing into better methods to diagnose and treat
      infection. SUMMARY: CIED-related infections are an important clinical problem
      with ongoing research to improve diagnosis and treatment. Currently, percutaneous
      CIED extraction and antibiotic therapy are the mainstay of treatment.

PMID- 21076289
TI  - Phrenic stimulation management in CRT patients: are we there yet?
AB  - PURPOSE OF REVIEW: Phrenic stimulation may hinder left-ventricular (LV)
      stimulation and prevent cardiac resynchronization therapy (CRT) delivery. We
      reviewed the literature to address its prevalence and clinical implications in
      CRT patients. RECENT FINDINGS: Phrenic stimulation prevalence ranges from 20 to
      33% of patients when a posterolateral LV lead placement is aimed. False-negatives
      are common during implantation, sensitivity being about 60-80%. Symptoms may
      dictate repositioning the LV lead, meaning risk of lead dislodgement, decreased
      CRT efficacy, or high LV threshold. CRT turn-off occurred in 2% of patients
      because of refractory phrenic stimulation. Several strategies have been used to
      manage phrenic stimulation: whereas lead repositioning was the only one available
      in early CRT experience, the use of bipolar/multipolar leads combined with
      cathode programmability enabling several pacing configurations has made possible
      targeting the optimal LV pacing sites in nearly all patients.Despite
      technological improvements, phrenic stimulation symptoms are sporadically
      reported by 6-8% of patients at follow-up, meaning that there is still an unmet
      need to address this problem. SUMMARY: Phrenic stimulation needs to be carefully
      managed at implantation and follow-up. Use of bipolar/multipolar leads and of
      multiple pacing configurations is mandatory to increase the chances of managing
      phrenic stimulation. Active fixation LV leads, hopefully bipolar, could further
      increase the success rate.

PMID- 21076286
TI  - Decreased mortality resulting from a multicomponent intervention in a tertiary
      care medical intensive care unit.
AB  - OBJECTIVE: To evaluate whether a multicomponent intervention, particularly
      increasing staff, can achieve reductions in patient mortality in an already high
      intensity, Leapfrog-compliant medical intensive care unit. DESIGN: Retrospective,
      observational study. SETTING: Medical intensive care unit of a tertiary care,
      academic medical center. PATIENTS: A total of 1,263 patients admitted between
      April 19, 2004 and April 18, 2006 (before the organizational change) were
      compared with 2,424 patients admitted between September 5, 2006 and September 4,
      2008. INTERVENTIONS: A multicomponent intervention including the physical move
      from a 10-bed to a 29-bed medical intensive care unit with larger patient rooms,
      the initiation of 24-hr critical care specialist coverage in the medical
      intensive care unit, an increase in the respiratory therapist:patient ratio, and
      the addition of a clinical pharmacist to the multidisciplinary team. MEASUREMENTS
      AND MAIN RESULTS: Measurements were made based on mortality in the intensive care
      unit and in-hospital. Patient comorbidity as measured by the Charlson score did
      not change after the intervention (2.7 +/- 2.7 vs. 2.8 +/- 2.6, p = .62), nor did
      the acuity of illness as measured by the case mix index (3.0 +/- 3.7 vs. 3.1 +/-
      3.8, p = .69). The unadjusted medical intensive care unit mortality decreased
      from 18.4% to 14.9% (p = .006), as did in-hospital mortality (from 25.8% to
      21.7%, p = .005). The reduction in medical intensive care unit mortality was
      consistent in the multivariable regression with adjustment for multiple possible
      confounders (odds ratio = 0.74, 95% confidence interval: 0.61-0.91, p = .003), as
      was the reduction in hospital mortality (odds ratio = 0.74, 95% confidence
      interval: 0.62-0.88, p = .001). In mechanically ventilated patients, there was an
      increase in median 28-day ventilator-free days (21, interquartile range 0-25 vs.
      22, interquartile range 0-26, p = .04). An increase in median medical intensive
      care unit (2.4, interquartile range 1.1-5.2 vs. 2.7, interquartile range 1.3
      5.9), p = .009) but not hospital (8.3, interquartile range 4.1-17.0 vs. 8.2,
      interquartile range 4.0-16.8; p = .851) length of stay in days occurred with the
      intervention. The mean daily dosing of fentanyl and lorazepam decreased after the
      intervention. CONCLUSIONS: A multicomponent reorganization of medical intensive
      care unit services was associated with important reductions in mortality for
      medical intensive care unit patients, as well as an increased number of
      ventilator-free days. Substantial and sustained changes in clinically important
      outcomes may be obtained from organizational changes.

PMID- 21076290
TI  - Management of arrhythmias in patients with tetralogy of Fallot.
AB  - PURPOSE OF REVIEW: Patients with tetralogy of Fallot are subject to arrhythmic
      sequelae that substantially impact morbidity and mortality. This review focuses
      on recent advances in our understanding of the prevalence and types of
      arrhythmias encountered. Diagnostic and prognostic tools are considered and
      therapeutic options discussed. RECENT FINDINGS: Multicenter studies have
      characterized the arrhythmia burden, assessed the impact of implantable
      cardioverter-defibrillators, and generated a risk score for primary prevention.
      Left ventricular hemodynamics are increasingly recognized as important
      contributors to risk for sudden death. Arrhythmia circuits have been
      characterized, and the impact of pulmonary valve replacement on sudden death has
      been further questioned. Recent studies cast doubt on the value of right
      ventricular pacing alone for cardiac resynchronization and provide a rationale
      for biventricular pacing. SUMMARY: Supraventricular arrhythmias exceed
      ventricular arrhythmias in prevalence, as atrial fibrillation increases with the
      aging population. Sudden death is the leading cause of late mortality, although
      therapeutic advances may alter this profile. Combinations of factors should be
      considered in risk stratification schemes to select appropriate implantable
      cardioverter-defibrillator candidates. The role of concomitant intraoperative
      ablation during pulmonary valve replacement surgery remains to be defined.
      Cardiac resynchronization therapy, particularly biventricular pacing, offers
      promise, but requires careful study before widespread implementation.

PMID- 21076292
TI  - Taurine in cardiovascular disease.
AB  - PURPOSE OF REVIEW: The shift of modern dietary regimens from 'Mediterranean' to
      'western' style is believed to be responsible, in part, for the increase in
      cardiovascular disease, obesity, type II diabetes and cancer. A classic
      'Mediterranean' diet consists of adequate intake of seafood, vegetables, fruit,
      whole grain and nonpurified monounsaturated vegetable oil. Thus, in humans,
      dietary intake of seafood is the major source of taurine, as the level of
      endogenously produced taurine is low. RECENT FINDINGS: Taurine has been shown to
      affect coronary artery disease, blood pressure, plasma cholesterol and myocardial
      function in animal models of human disease. A major role of taurine is to act as
      an antioxidant and absorb hypochlorous acid but not the oxidative radical. It
      seems that this beneficial effect of taurine in antioxidant therapy has not been
      well promoted. SUMMARY: This review will focus on determining whether taurine
      could be a factor contributing to the further prevention of heart disease.

PMID- 21076291
TI  - Amino acid composition in parenteral nutrition: what is the evidence?
AB  - PURPOSE OF REVIEW: Complete parenteral nutrition solutions contain mixed amino
      acid products providing all nine essential amino acids and a varying composition
      of nonessential amino acids. Relatively little rigorous comparative efficacy
      research on altered parenteral nutrition amino acid composition has been
      published in recent years. RECENT FINDINGS: Limited data from randomized, double
      blind, adequately powered clinical trials to define optimal doses of total or
      individual amino acids in parenteral nutrition are available. An exception is the
      growing number of studies on the efficacy of glutamine supplementation of
      parenteral nutrition or given as a single parenteral agent. Parenteral glutamine
      appears to confer benefit in selected patients; however, additional data to
      define optimal glutamine dosing and the patient subgroups who may most benefit
      from this amino acid are needed. Although some promising studies have been
      published, little data are available in the current era of nutrition support on
      the clinical efficacy of altered doses of arginine, branched chain amino acids,
      cysteine, or taurine supplementation of parenteral nutrition. SUMMARY: Despite
      routine use of parenteral nutrition, surprisingly little clinical efficacy data
      are available to guide total or specific amino acid dosing in adult and pediatric
      patients requiring this therapy. This warrants increased attention by the
      research community and funding agencies to better define optimal amino acid
      administration strategies in patient subgroups requiring parenteral nutrition.

PMID- 21076293
TI  - Association between increased tryptophan degradation and depression in cancer
      patients.
AB  - PURPOSE OF REVIEW: A high percentage of patients with malignant disease develops
      mood disorders or even depression. This review provides an overview, how immune
      activation and tryptophan degradation might contribute to the development of
      depression. RECENT FINDINGS: Neurobiochemical changes caused by immune activation
      are supposed to be involved in the development of mood disorders, especially
      depression, in cancer patients. Within Th1-type immune response the enzyme
      indoleamine 2,3-dioxygenase (IDO) is induced, which degrades the essential amino
      acid tryptophan to form kynurenine derivatives. Enhanced immune-mediated
      tryptophan degradation is reflected by decreased plasma tryptophan levels and
      increased kynurenine concentrations in parallel with elevated concentrations of
      Th1-type immune activation marker neopterin. IDO activation has been demonstrated
      in patients with various kinds of cancer, and it has also been shown to predict a
      worse outcome of patients. Recent data also indicate strongly, that immune
      mediated tryptophan degradation is crucially involved in the development of
      depression: IDO activation leads to the accumulation of neurotoxic metabolites,
      which are supposed to induce depressive-like behaviour. Furthermore immune
      mediated tryptophan deprivation might also impair serotonin synthesis, as
      tryptophan is the precursor of this important neurotransmitter. SUMMARY: Immune
      mediated tryptophan degradation appears to be crucially involved in the
      development of depression.

PMID- 21076295
TI  - Cachexia versus sarcopenia.
AB  - PURPOSE OF REVIEW: The review summarizes and discusses the proposed new
      definitions for sarcopenia and cachexia. It also highlights the overlapping of
      both conditions and the fact that these conditions frequently occur in elderly
      patients. RECENT FINDINGS: Sarcopenia is now recognized as a multifactorial
      geriatric syndrome. Cachexia is defined as a metabolic syndrome in which
      inflammation is the key feature and so cachexia can be an underlying condition of
      sarcopenia. Recently, cachexia has been defined as 'a complex metabolic syndrome
      associated with underlying illness and characterized by loss of muscle mass with
      or without loss of fat mass. The prominent clinical feature of cachexia is weight
      loss in adults'. Different recommendations have been proposed for the diagnosis
      of sarcopenia. At present, all definitions combine an assessment of muscle mass
      and muscle function (strength or physical performances such as gait speed).
      However, the relevance and the validation of these evolving definitions need to
      be assessed in future studies. SUMMARY: Although the recent definitions of
      sarcopenia and cachexia boost research in the field and define distinct entities,
      the cause behind the loss of muscle mass (whether cachexia or sarcopenia) may,
      however, be indistinguishable in clinical practice. Therefore, new therapeutic
      approaches, alone or in combination, could be targeted on both conditions.

PMID- 21076296
TI  - Advances in the diagnosis and treatment of chronic granulomatous disease.
AB  - PURPOSE OF REVIEW: Chronic granulomatous disease (CGD), characterized 50 years
      ago as a primary immunodeficiency disorder of phagocytic cells (resulting in
      failure to kill a defined spectrum of bacteria and fungi and in concomitant
      chronic granulomatous inflammation) now comprises five genetic defects impairing
      one of the five subunits of phagocyte NADPH oxidase (Phox). Phox normally
      generates reactive oxygen species (ROS) engaged in intracellular and
      extracellular host defence and resolving accompanying inflammatory processes.
      'Fatal' granulomatous disease has now changed into a chronic inflammatory
      condition with a median survival of 35 years and is now of interest to both
      paediatricians and internists. Clinical vigilance and expert knowledge are needed
      for early recognition and tailored treatment of this relatively rare genetic
      disorder. RECENT FINDINGS: Infections by unanticipated pathogens and noncirrhotic
      portal hypertension need to be recognized as new CGD manifestations. Adult-onset
      CGD too is increasingly observed even in the elderly. Conservative treatment of
      fungal infections needs close monitoring due to the spread of azole resistance
      following extensive use of azoles in agriculture. Curative haematopoietic stem
      cell transplantation (HSCT) in early childhood has expanded with impressive
      results following use of matched, unrelated or cord blood donors and of a reduced
      intensity conditioning (RIC) regimen. Gene therapy, however, still has major
      limitations, remaining experimental. SUMMARY: CGD is more prevalent than
      initially believed with a birth prevalence of 1: 120 000. As patients are
      increasingly diagnosed around the world and grow older, further manifestations of
      CGD are expected. While fungal infections have lost some threat, therapeutic
      research focuses on two other important aims: pharmacologic cure of chronic
      inflammation and long-term cure of CGD by gene therapy.

PMID- 21076294
TI  - Essential amino acid sensing, signaling, and transport in the regulation of human
      muscle protein metabolism.
AB  - PURPOSE OF REVIEW: To highlight the recent research pertaining to the cellular
      mechanisms linking amino acid availability, mTORC1 signaling, and muscle protein
      metabolism. RECENT FINDINGS: Activation of the mTORC1 pathway in response to
      amino acids may be dependent upon cellular relocalization of mTORC1, a process
      that appears to involve the Rag GTPases. Recent studies have also identified
      other intracellular proteins, such as hVps34 and MAP4K3, and specific amino acid
      transporters as necessary links between amino acid availability and mTORC1. In
      human skeletal muscle, it appears that mTORC1 activity increases the expression
      of several amino acid transporters, which may be an important adaptive response
      to sensitize muscle to a subsequent increase in amino acid availability. SUMMARY:
      The precise cellular mechanisms linking amino acids to mTORC1 signaling and
      muscle protein metabolism are currently not well understood. More defined
      cellular mechanisms are beginning to emerge suggesting a role for several
      intracellular proteins including hVps34, MAP4K3, and Rag GTPases. Additionally,
      specific amino acid transporters may have a role both upstream and downstream of
      mTORC1. Continued investigation into the precise cellular mechanisms linking
      amino acid availability and muscle protein metabolism will help facilitate
      improvements in existing therapies for conditions of muscle wasting.

PMID- 21076297
TI  - Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome.
AB  - PURPOSE OF REVIEW: The Wiskott-Aldrich syndrome (WAS), caused by mutations in the
      WAS gene, is a complex and diverse disorder with X-linked inheritance. This
      review focuses on recent developments in the understanding of its basic
      pathophysiology, diverse clinical phenotypes and optimal patient management
      including novel therapies. RECENT FINDINGS: The protein encoded by the WAS gene
      is a multifunctional signaling element expressed in immune and hematopoietic
      cells that plays a critical role in cytoskeletal reorganization, immune synapse
      formation and intracellular signaling. The type of specific mutation, its
      location within the gene and its effect on protein expression play a major role
      in determining an individual patient's clinical phenotype. Recent clinical
      observations and molecular studies have created a sophisticated picture of the
      disease spectrum. The improved outcome of stem cell transplantation from related
      and unrelated matched donors and promising early results from the first clinical
      gene therapy trial have added new therapeutic options for these patients.
      SUMMARY: Classic WAS, X-linked thrombocytopenia and X-linked neutropenia are
      caused by WAS gene mutations, each having a distinct pattern of clinical symptoms
      and disease severity. New developments in the understanding of these syndromes
      and novel therapeutic options will have a major impact on the treatment of
      individuals with WAS mutations.

PMID- 21076298
TI  - New insights into angiotensin receptor actions: from blood pressure to aging.
AB  - PURPOSE OF REVIEW: The renin-angiotensin system (RAS) is critical for
      cardiovascular control, impacting normal physiology and disease pathogenesis.
      Although several biologically active peptides are generated by this system, its
      major actions are mediated by angiotensin II acting through its type 1 (AT1) and
      type 2 (AT2) receptors. Along with their effects to influence blood pressure and
      hemodynamics, recent studies have provided evidence that angiotensin receptors
      influence a range of processes independent from hemodynamic effects. RECENT
      FINDINGS: This review is focused on new molecular mechanisms underlying actions
      of AT1 receptors to influence vasoconstriction, inflammation, immune responses,
      and longevity. Moreover, we also highlight new advances in understanding
      functions of the AT2 receptor in end-organ damage, emphasizing the AT2 receptor
      as a potential therapeutic target in cardiovascular diseases. SUMMARY: Here we
      review recent advances in understanding the role of angiotensin receptors in
      normal physiology and disease states, focusing on their properties that may
      contribute to blood pressure regulation, end-organ damage, autoimmune disease and
      longevity.

PMID- 21076300
TI  - Biobanking: the foundation of personalized medicine.
AB  - PURPOSE OF REVIEW: Biobanking has been identified as a key area for development
      in order to accelerate the discovery and development of new drugs. This review
      describes the recent advances in the field of biobanking and biospecimen
      research, with special reference to tumour banks which are the biobanks of
      primary interest in oncology. RECENT FINDINGS: There is a dramatic deficiency of
      high-quality, well annotated cancer biospecimens. Biospecimen research is a fast
      developing field that will improve biobanking methodology and biobanking is
      becoming more professionally organized with increased attention to quality
      management. Biobank networks are developing rapidly in order to combine and share
      resources. SUMMARY: Biobanking services must improve rapidly to serve the needs
      of personalized medicine and biospecimen research should be encouraged and
      supported at all levels from project funding to publication of results. Biobanks
      need to be run to high professional standards and the importance of adequate
      funding, training and certification must be emphasized. The growing presence of
      national and international biobank networks will allow biobanks to synergize. The
      development of a biobanking community will facilitate teamwork to overcome common
      challenges and enhance communication with multiple stakeholder groups.

PMID- 21076299
TI  - Rho kinase inhibition in diabetic nephropathy.
AB  - PURPOSE OF REVIEW: The Rho GTPases and their downstream effectors Rho-associated
      kinases (ROCKs) appear to be the molecules that converge numerous
      pathophysiological signals triggered by the diabetic milieu and represent
      promising molecular targets for nephroprotective treatment in diabetes. The
      review discusses recent studies exploring the consequences of diabetes-induced
      Rho-ROCK activation in the kidney and the effects of ROCK inhibition (ROCKi) in
      experimental diabetic nephropathy. RECENT FINDINGS: Recent studies in models of
      type 1 and type 2 diabetes have indicated blood-pressure-independent
      nephroprotective actions of ROCKi in diabetic nephropathy. The underlying
      mechanisms include attenuation of diabetes-induced increases in renal expression
      of prosclerotic cytokines and extracellular matrix, resulting in slower
      development of glomerulosclerosis and interstitial fibrosis. The studies have
      also shown antiproteinuric affects of ROCKi that could be related to reductions
      in permeability of glomerular barrier and beneficial effects on podocytes.
      Moreover hemodynamic mechanisms might be also involved. SUMMARY: Despite
      remaining questions in this field, such as the specificity of currently available
      ROCKi, or the roles of individual ROCK isoforms, recent evidence in experimental
      diabetes, together with evidence generated in models of nondiabetic kidney
      disease and in clinical studies in patients with various cardiovascular
      disorders, suggest that ROCKi might in future broaden the spectrum of treatments
      available for patients with diabetic nephropathy.

PMID- 21076301
TI  - Genome-based and transcriptome-based molecular classification of breast cancer.
AB  - PURPOSE OF REVIEW: The highly heterogeneous clinical, histological, biological
      and genetic nature of breast malignancies is due in part to their extreme
      molecular complexity. RECENT FINDINGS: Many genetic and epigenetic alterations
      have been described, affecting a relatively small number of signaling pathways
      (PI3K, NK-kappaB, FGF, etc.) and thus several molecular subtypes of breast cancer
      have been identified. SUMMARY: The next decade will see even more prolific
      developments, notably with the advent of next-generation sequencing (NGS)
      technologies capable of providing individual patients' constitutional and somatic
      genome sequences both rapidly and cheaply. Knowledge of the full catalogue of
      somatic genetic alterations will pave the way for fully individualized management
      of breast cancer patients.

PMID- 21076302
TI  - Integrating biomarkers into clinical trials: methodological issues for a new
      paradigm in nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: To summarize the major methodological issues concerning
      prognostic biomarkers in nonsmall cell lung cancers (NSCLCs) and to discuss
      integration of biomarkers into clinical trials. RECENT FINDINGS: Large phase 3
      trials have recently been published in early-resected NSCLC with studies of
      biomarkers identifying subsets of patients that benefited most from the
      experimental perioperative strategy. The IALT-bio study reported that ERCC1 DNA
      repair protein had prognostic and predictive implications. Other studies reported
      on the prognostic role of TUBB3 expression in stages I-III NSCLCs. The IPASS
      study reported the predictive and prognostic impact of epidermal growth factor
      receptor (EGFR) mutations in stage IV patients treated with EGFR tyrosine kinase
      inhibitor or platinum-based chemotherapy. Whereas EGFR mutations studies received
      prospective validation with trials in which treatment allocation was based on
      biomarker status, chemotherapy biomarkers still need such prospective
      confirmations, and many biases were still encountered in recent published
      studies. SUMMARY: Biomarkers of treatment efficacy will help to tailor treatment
      in NSCLCs. EGFR mutations have reached that point. Markers of chemotherapy
      efficacy still need validation studies before coming into routine practice.
      Stringent methodological recommendations should avoid most of the possible
      pitfalls of those studies and allow clinical applicability of such biomarkers.

PMID- 21076304
TI  - Diagnosis and management of pituitary adenomas.
AB  - PURPOSE OF REVIEW: Pituitary adenomas are frequently encountered in practice
      either because of clinical symptoms or as incidental findings. These tumors may
      alter pituitary function and can therefore have a considerable impact on
      morbidity, mortality, and quality of life. RECENT FINDINGS: The presentation is
      variable for each type of tumor, with microadenomas being either silent or
      manifesting with symptoms of hormonal excess. In contrast, macroadenomas may
      present with mass effect. The various histologic types include prolactinomas,
      nonfunctioning adenomas, somatotropinomas, corticotropinomas, and
      thyrotropinomas. The present article will serve as an update on the diagnosis and
      treatment of pituitary adenomas. Advances in medical management for each tumor
      are discussed, highlighting new therapeutic alternatives. The role of surgery is
      also reviewed. Recommendations on the surveillance and postoperative monitoring
      of patients are emphasized. SUMMARY: Newer methods in the diagnosis and treatment
      for pituitary adenomas greatly expand our ability to care for affected patients.

PMID- 21076303
TI  - Integrating biomarkers into molecular epidemiological studies.
AB  - PURPOSE OF REVIEW: Biomarkers play a central role in chronic disease
      epidemiology, providing insights into pathways related to the relationship
      between environmental exposures and disease risk. Recent developments in both
      data acquisition techniques and laboratory approaches advocate for a more
      extensive and refined use of biomarkers. RECENT FINDINGS: We review some issues
      related to biomarker identification and validation techniques as well as the main
      methodologies to measure biomarkers in existing biobank data. Finally, we
      describe analytical strategies recently proposed to include the time component
      into biomarker research. SUMMARY: This review suggests that some of the technical
      issues to identify, validate, and analyze biomarkers have been partly addressed
      in epidemiological studies. The inclusion of biomarker analyses into longitudinal
      frameworks provides a promising potential to analyze the role of different types
      of biomarkers and to refine the 'causal' models linking exposure to disease risk.
      These kinds of approaches can be implemented based on existing cohort data, at
      the cost of some approximation, but their generalization would ideally require
      advancements in study design, such as routinely allowing for the collection of
      several biological samples at different time points.

PMID- 21076305
TI  - Functional visual acuity measurement in cataract and intraocular lens
      implantation.
AB  - PURPOSE OF REVIEW: Recently, functional visual acuity (FVA) measurement has been
      reported to be an important method of determining 'masked impairment of visual
      function' and assessing visual acuity in detail. This review discusses a new
      continuous FVA measurement system for the assessment of visual performance and
      introduces the application of FVA measurement in cataract and intraocular lens
      implantation. RECENT FINDINGS: The FVA was first developed to detect impaired
      visual function for daily activities in dry eye syndrome. The usefulness of this
      new methodology has been described in patients with tear instability, undergoing
      laser-assisted in-situ keratomileusis surgery, with Stevens-Johnson syndrome,
      Sjogren syndrome and mild cataract opacities. The microstructure of the
      lenticular opacities is highly variable (nucleus sclerosis and/or posterior
      capsular cataract and/or cortical opacity) causing a combination of different
      effects on the incident light rays that can be refracted, reflected, absorbed or
      scattered. In some cases, patients have a good visual acuity but may complain of
      disturbances in vision quality. We reported the improvement of FVA after cataract
      surgery in patients with mild cataracts and visual symptomatology despite a good
      preoperative and postoperative conventional visual acuity. To detect visual
      impairment due to cataract, measurement of FVA was useful in the evaluation of
      vision quality and changes in kinetic vision after phacoemulsification surgery.
      SUMMARY: FVA measurement is an effective and noninvasive test that reflects the
      complaints of blurring/glare and postoperative satisfaction in patients with mild
      cataract.

PMID- 21076306
TI  - Consequences of waiting for cataract surgery.
AB  - PURPOSE OR REVIEW: To conduct a concise review of primary research articles over
      the preceding year on the subject of the consequences of waiting for cataract
      surgery. RECENT FINDINGS: Waiting for cataract surgery beyond 6 months may result
      in increasing vision loss, decrease in quality life, loss of driver's license,
      depression and adverse events including falls and fractures. The consequences of
      waiting for cataract surgery not only affect patients, families and surgeons, but
      also health ministries and public health policy makers. Consequences are both
      quantitative and qualitative in nature, ranging from progressive vision loss to
      patients' decrease in quality of life from factors other than vision loss.
      Cataract wait lists are not unique to North America, and numerous international
      articles have described a broad variety of consequences. SUMMARY: Consequences of
      waiting for cataract surgery are multivariate in nature and easily extend beyond
      the clinical setting into sociodemographic realms and public health costs and
      policy arenas.

PMID- 21076307
TI  - Medical, psychological, and sociodemographic factors associated with adherence to
      cardiac rehabilitation programs: a systematic review.
AB  - OBJECTIVES: Cardiac rehabilitation (CR) programs have been shown to reduce
      mortality and morbidity rates among coronary heart disease patients, but
      adherence to these classes has been found to be poor. This review aims to
      summarize and integrate research findings investigating the possible
      sociodemographic, medical, and psychological variables that influence patient
      adherence to CR programs. It also aims to address the methodological failings of
      past reviews conducted in this area. METHODS: Several databases were
      systematically searched for studies published between 1990 and 2009. Studies
      examining CR program adherence or completion, using data based on participant's
      actual recorded attendance were included. RESULTS: Eighteen studies were
      identified that met inclusion criteria. Low mood, participant's age, and certain
      cardiac risk factors were found to be most consistently associated with poor
      adherence to CR. A good understanding of the consequences of heart disease was
      found to be associated with good adherence. Results were relatively inconsistent
      across studies because of differences in methods used. CONCLUSIONS: Certain risk
      factors for poor adherence to CR should be assessed and monitored by health
      professionals. Future studies should address the methodological difficulties
      present in previous research. Recommendations are made for standardizing methods
      in future research.

PMID- 21076308
TI  - Educational interventions for patients with heart failure: a systematic review of
      randomized controlled trials.
AB  - BACKGROUND: Patient education is an important intervention for the management of
      heart failure; however, in practice patient education varies considerably. AIM: :
      To systematically review educational interventions that have been implemented for
      heart failure patients and assess their effectiveness. METHODS: Randomized
      controlled trials from 1998 to 2008 in CINAHL, MEDLINE, PsychInfo, EMBASE, and
      Cochrane were reviewed using the following search terms: patient education,
      education, educational intervention, self-care in combination with heart failure.
      There were 1515 abstracts reviewed independently by 2 reviewers. RESULTS: A total
      of 2686 patients were included in the 19 studies that met the inclusion criteria.
      Commonly, the initial educational intervention was a one-on-one didactic session
      conducted by nurses supplemented by written materials and multimedia approaches.
      Seven studies referred to a theoretical model as a framework for their
      educational intervention. Studies used a variety of outcome measures to evaluate
      their effectiveness. Of the studies reviewed, 15 demonstrated a significant
      effect from their intervention in at least one of their outcome measures.
      CONCLUSION: All we hope from patient education has not yet been realized. Despite
      improvements in knowledge, we have variable results in outcomes, and this is very
      likely related to the heterogeneity of the studies included in this review. It
      was difficult to establish the most effective educational strategy as the
      educational interventions varied considerably in delivery methods and duration as
      well as the outcome measures that were used for the evaluation. A patient
      centered approach to education based on educational theory and evaluated
      appropriately may assist to develop an evidence base for patient education.

PMID- 21076309
TI  - A critical link between heart failure self-care and intrathoracic impedance.
AB  - BACKGROUND: Effective self-care is regarded as essential to the management of
      heart failure (HF). The influence of self-care on HF decompensation, however, is
      not well understood. Accordingly, we examined the relationship between self-care
      and fluid accumulation accompanying worsening HF as indexed by decreasing
      intrathoracic impedance (Z). METHODS: Z data were collected from 58 HF patients
      with OptiVol enabled devices (Medtronic Inc, Minneapolis, Minnesota). Heart
      failure self-care was measured with the European Heart Failure Self-care
      Behaviour Scale. Regression modeling was used to describe the influence of HF
      self-care on the likelihood of a fluid index (FI) threshold crossing, the number
      of threshold crossings, and number of days spent above threshold. RESULTS:
      Patients were elderly (74.98 [SD, 8.12] years), with a mean left ventricular
      ejection fraction of 26.21% (SD, 9.77%), and 63.7% had class New York Heart
      Association III HF. Patients were followed up for 317 (SD, 96) days; 65.5% had FI
      threshold crossings (mean 1.45 [SD, 1.56] crossings), spending an average of 33.8
      (SD, 42.4) days above FI threshold. Controlling for age, sex, left ventricular
      ejection fraction, functional class, and duration of follow-up, each additional
      point on the European Heart Failure Self-care Behaviour Scale was associated with
      an increase in the odds of having had an FI threshold crossing (adjusted odds
      ratio, 1.201; 95% confidence interval, 1.013-1.424; P<.05) and more days spent
      above FI threshold (incidence rate ratio, 1.051; 95% confidence interval, 1.002
      1.102; P<.05). CONCLUSION: Intrathoracic impedance measurements obtained from
      implantable devices provide important information regarding the influence of self
      care on fluid accumulation in patients with HF.

PMID- 21076310
TI  - Awareness of hypertension guidelines in Taiwanese nurses: a questionnaire survey.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Nurses play an important role in hypertension
      prevention and management because of their unique positions in patient education.
      However, the effectiveness of patient education relies largely on the nurse's
      level of awareness of the current hypertension guidelines. The purpose of this
      study was to examine the level of awareness of hypertension guidelines and
      associated factors among nurses in Taiwan. SUBJECTS AND METHODS: A cross
      sectional survey was conducted in 10 hospitals in northern Taiwan. The
      Hypertension Management Questionnaire was developed based on the Taiwan
      Hypertension Guidelines and the seventh report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. RESULTS:
      The survey return rate was 95.9%. A total of 1418 nurses were included in the
      analysis. Adequate guideline awareness was found in 49.5% of the total sample.
      Among the 7 dimensions of the Hypertension Management Questionnaire, the
      definition of hypertension, methods for blood pressure measurements, and impact
      of high blood pressure on cardiovascular disease had the lowest rates of correct
      answers. Multiple regression analysis revealed that the nurses' clinical
      experience, educational level, work setting, in-service education training on
      hypertension, and level of the hospital (R2 = 35.4%, F = 52.89, P < .001)
      independently predicted the nurse's level of awareness. CONCLUSIONS: A large
      proportion of the nurses in northern Taiwan had insufficient knowledge of the
      hypertension guidelines.

PMID- 21076311
TI  - A home-based exercise program improves heart rate variability and functional
      capacity among postmenopausal women with coronary artery disease.
AB  - AIMS: To determine whether a home-based exercise program is able to increase
      functional capacity (FC) and reduce heart rate variability (HRV) in
      postmenopausal women with coronary heart disease. BACKGROUND: Regular exercise
      training has been shown to improve both FC and HRV. However, those studies were
      conducted within institutional training programs, and few have included women.
      METHODS: Thirty-two postmenopausal women were randomly assigned to either an
      experimental or control group with 16 participants in each group. Those in the
      experimental group underwent home-based exercise training, 3 times a week for 8
      weeks. On the first and final week, each participant's HRV was measured, and
      their FC was evaluated using a 6-minute walking test. FINDINGS: After 8 weeks,
      the FC of those who had undergone the home-based exercise program showed a
      significant improvement compared with subjects in the control group (P = .001).
      The total power (ms2), high-frequency (ms2), and low-frequency (ms2) indexes of
      HRV were also significantly improved over control values. CONCLUSION: In
      postmenopausal women with coronary heart disease, a home-based exercise program
      appears able to improve FC and HRV.

PMID- 21076312
TI  - The impact of sleep quality and daytime sleepiness on global quality of life in
      community-dwelling patients with heart failure.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Although it is well established that symptom
      burden in heart failure (HF) often leads to poor health-related quality of life
      (QOL), the contributions of quality of sleep and daytime sleepiness to the
      overall perception and satisfaction with life in the HF population have yet to be
      determined. We thus tested the hypothesis that quality of sleep and daytime
      sleepiness are significant predictors of QOL as measured by the World Health
      Organization Quality of Life-BREF (WHOQOL-BREF) in patients with HF. SUBJECTS AND
      METHODS: Included were 88 medically stable patients with echocardiographically
      documented HF. This cross-sectional study used a correlational design, and data
      were collected using self-report questionnaires including the Chinese version of
      the Pittsburgh Sleep Quality Index (CPSQI), Epworth Sleepiness Scale, and WHOQOL
      BREF Taiwan version. Multiple linear regression analyses were used to address the
      study hypotheses. RESULTS AND CONCLUSIONS: With the exception of the
      environmental domain (P = .078), poor sleepers had significantly lower scores in
      physical (P < .001), psychological (P = .001), and social (P = .040) domains of
      the WHOQOL-BREF. Multivariate regression analysis revealed that age, CPSQI,
      perceived health status, and comorbidities significantly predicted the physical
      QOL (adjusted R2 = 0.59, P < .001). For the psychological QOL, only perceived
      health status and CPSQI score remained in the regression model (adjusted R2 =
      0.28, P = .016). For the environmental QOL, perceived health status and Epworth
      Sleepiness Scale were the only predictors remaining in the model (adjusted R2 =
      0.17, P < .001). The findings from this study add support to the evidence that in
      medically stable persons with HF, poor sleep independently predicts the overall
      perception and satisfaction with life, in particular, in the physical and
      psychological domains of QOL, whereas daytime sleepiness independently predicts
      the environmental QOL.

PMID- 21076313
TI  - Geographic analysis of cardiac interventional services in Alabama.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death in the state of
      Alabama. The purpose of this study was to explore the geographical accessibility
      of the Alabama population to cardiac interventional services (CISs) for the
      treatment of acute myocardial infarction. METHODS: A descriptive ecological study
      design was used. Census tract-level population census data were used to describe
      access to CIS in Alabama. Descriptive analysis was conducted within a
      geographical information system (GIS) and provided empirical measures of travel
      time, calculated population proportions, and generated maps for visual
      identification of areas of low access. Descriptive statistics are reported as
      proportions (percentages) of the population with access by travel time. FINDINGS:
      The GIS analysis revealed that 58.2%, 85.9%, and 96.0% of the total Alabama
      population were within 30-, 60-, or 90-minute travel time, respectively, of a
      hospital with CIS. Maps provided visualization of CIS coverage areas for Alabama.
      One distinct area within the Alabama Black Belt was at greater than 90 minutes
      from a hospital with CIS. This area is known as a mostly black, impoverished
      population subject to health disparities. CONCLUSIONS: The GIS showed that 96% of
      the Alabama population is within 90-minute travel time of a hospital with CIS.
      For the best outcomes to occur allowing adequate time for symptom recognition,
      travel time, and 30-minute door-to-needle time, only 85.9% and 58.2% are within
      60- and 30-minute travel time, respectively.

PMID- 21076314
TI  - Predictors of modifications in instrumental activities of daily living in persons
      with heart failure.
AB  - OBJECTIVES: The objective of this study was to identify factors related to
      disability in heart failure (HF) patients using a modified version of the model
      of disability proposed by Nagi. The hypothesized relationships among pathology
      (severity of HF and comorbidity), impairment (dyspnea, fatigue, muscle strength),
      functional limitation (functional capacity), and disability (modification in
      instrumental activities of daily living [IADLs]) were assessed as well as the
      influence of age and sex on pathways to disability. METHODS AND RESULTS: Using a
      cross-sectional design, a convenience sample of 48 men and 53 women (mean age,
      59.5 years) with New York Heart Association class II-IV was recruited at a HF
      clinic. Path analyses via Amos revealed that 71% of the variance in modifications
      in IADLs was explained by the significant predictors of dyspnea (B = .67),
      functional capacity (B = -.25), and age (B = .19). Dyspnea and comorbidity also
      had indirect effects on modification in IADLs through functional capacity. Age
      also had an indirect effect on modification in activities of daily living through
      functional capacity, and sex had an indirect effect through dyspnea and
      functional capacity. CONCLUSION: Patients with HF may benefit from interventions
      targeted at reducing dyspnea with daily activities and improving functional
      capacity to prevent disability.

PMID- 21076315
TI  - Does nurse case management improve implementation of guidelines for
      cardiovascular disease risk reduction?
AB  - BACKGROUND AND OBJECTIVE: Over the last 5 decades, research has demonstrated that
      cardiovascular risk reduction mediated through medical and surgical therapies, as
      well as lifestyle change, reduces morbidity and mortality from diseases of the
      vascular system. Based on this extensive research, government and professional
      organizations publish evidence-based guidelines for the management of patients
      with, or at risk of developing, cardiovascular disease. However, recommended
      interventions are frequently neither initiated nor adhered to, and when
      appropriate therapies are initiated, patient adherence is poor. This review
      sought to evaluate how nurse-based case management (NCM) according to recommended
      guidelines improves patient outcomes and enhances cardiovascular risk reduction.
      METHODS: English-language articles (1950 to January 2009) were identified using a
      combination of the following terms: (case) management; nurse(-led) or nursing;
      guideline and/or implement or implementation; cardiovascular (disease) (risk);
      hypertension or dyslipidemia, or diabetes, or smoking (cessation), or
      nutritionist, or cardiac rehabilitation. Primary articles were reviewed for focus
      on modifiable risk factor management involving a nurse acting as a "case
      manager," having a prominent role within the management of a patient's
      cardiovascular health, and following scientifically based, published guidelines.
      FINDINGS AND CONCLUSION: From the Stanford Coronary Risk Intervention Project in
      the 1990 s to EUROACTION published 2008, NCM has appreciably evolved. The studies
      summarized demonstrate that individualized, systematic, and guideline-based NCM
      can translate into clinically meaningful reductions in cardiovascular-related
      morbidity and mortality. Furthermore, the NCM model was effective for
      hospitalized patients, especially during the postdischarge period, in primary
      care, low-income clinics, and in the community including the workplace. Providing
      NCM for those at risk of or with cardiovascular disease may help toward reducing
      the related loss of productive lives and the enormous costs to society.

PMID- 21076316
TI  - Effects of a cardiovascular risk reduction intervention with psychobehavioral
      strategies for Korean adults with type 2 diabetes and metabolic syndrome.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) and metabolic syndrome are associated
      with high risk of cardiovascular disease (CVD) and depression. Although lifestyle
      modifications including regular exercise and weight control are recommended as a
      primary approach to glycemic control and CVD risk reduction for people with DM
      and/or metabolic syndrome, little is known concerning the effects of CVD risk
      reduction interventions using psychobehavioral strategies in this population.
      OBJECTIVE: This pilot study investigated the effects of a 16-week CVD risk
      reduction intervention in Korean adults with type 2 DM and metabolic syndrome.
      METHODS: A prospective, pretest and posttest, controlled, quasi-experimental
      design enrolled a convenience sample of 43 Korean adults with type 2 DM and
      metabolic syndrome at a university hospital. The adults in the intervention group
      participated in a 16-week CVD risk reduction intervention consisting of 150
      minutes of regular exercise per week; 200- to 300-kcal reduced daily diet for
      weight control; one-on-one psychobehavioral counseling based on constructs from
      the Transtheoretical Model such as processes of change, self-efficacy, and
      decisional balance; and telephone coaching for behavioral modification.
      Participants in the control group received a booklet with basic diabetic
      education as part of their routine care. Repeated-measures analysis of variance
      was used for analyzing the effects of the CVD risk reduction intervention on
      cardiometabolic risk factors including the UK Prospective Diabetes Study score
      for 10-year CVD risk, glycated hemoglobin (HbA1c), and depression. RESULTS: The
      intervention group showed significant reductions (P < .05) at 16 weeks, compared
      with the control group on the UK Prospective Diabetes Study fatal risk scale (
      1.73% vs -0.04%), triglycerides (-38.5 vs -15.1 mg/dL), fasting plasma glucose (
      29.24 vs +1.77 mg/dL), HbA1c (-0.37% vs +0.17%), and depression (score, -3.24 vs
      1.40) measurements. CONCLUSIONS: This pilot study yielded evidence for the
      beneficial impact of the CVD risk reduction intervention for Korean adults with
      type 2 DM and metabolic syndrome on improved glycemic control, reduced CVD risk,
      and depression.

PMID- 21076317
TI  - Obstructive sleep apnea: a risk factor for cardiovascular disease.
AB  - Obstructive sleep apnea (OSA) is a condition in which the upper airway becomes
      constricted or occluded during sleep, leading to decreased or absent airflow,
      hypoxia, and sympathetic activation. This chain of events, occurring dozens of
      times an hour, can contribute to the development of hypertension, coronary artery
      disease, heart failure, and stroke. This article discusses the epidemiology of
      comorbid OSA and cardiovascular disease, the pathophysiology of OSA, how it acts
      as a risk factor for cardiovascular problems, and how appropriate treatment of
      OSA ameliorates the consequences. The importance of having a high suspicion for
      OSA in people with risk factors (including obesity, middle age, male or
      postmenopausal female) or symptoms (snoring, excessive daytime sleepiness,
      difficulty concentrating) is pointed out. The article concludes with clinical and
      research implications.

PMID- 21076318
TI  - Combining MEG and EEG source modeling in epilepsy evaluations.
AB  - This article reviews the relative strengths and weaknesses of MEG and EEG source
      modeling for localization of epileptogenic foci. Proper interpretation of these
      dipole models requires an appreciation for the limitations of each technique and
      an understanding of the character of the cortical sources that can generate
      epileptiform transients identifiable in recordings of spontaneous cerebral
      activity. MEG is sensitive to smaller sources, is not altered by the skull and
      scalp, requires a simpler head model, and provides more accurate localization,
      but it is insensitive to radial sources. EEG requires larger sources, is
      attenuated and smeared by the skull/scalp, requires a more complicated head
      model, and provides less accurate localization; however, and most importantly, it
      is sensitive to all source orientations. In conclusion, the case is made that
      maximal clinical information is obtained when simultaneous MEG and EEG are both
      subjected to source modeling, either individually or in a combined fashion.

PMID- 21076320
TI  - Tools for epilepsy research.

PMID- 21076319
TI  - N-methyl-D-aspartate-induced oscillatory properties in neocortical pyramidal
      neurons from patients with epilepsy.
AB  - N-Methyl-D-aspartate (NMDA) receptors have been implicated in epileptogenesis,
      but how these receptors contribute to epilepsy remains unknown. In particular,
      their role is likely to be complicated because of their voltage-dependent
      behavior. Here, the authors investigate how activation of NMDA receptors can
      affect the intrinsic production of oscillation and the resonance properties of
      neocortical pyramidal neurons from children with intractable epilepsy.
      Intracellular whole-cell patch clamp recordings in cortical slices from these
      patients revealed that pyramidal neurons do not produce spontaneous oscillation
      under control conditions. However, they did exhibit resonance around 1.5 Hz. On
      NMDA receptor activation, with bath-applied NMDA (10 MUM), the majority of
      neurons produced voltage-dependent intrinsic oscillation associated with a change
      in the stability of the neuronal system as reflected by the whole-cell I-V curve.
      Furthermore, the degree of resonance was amplified while the frequency of
      resonance was shifted to lower frequencies (~1 Hz) in NMDA. These results suggest
      that NMDA receptors may both promote the production of low-frequency oscillation
      and sharpen the response of the cell to lower frequencies. Both these behaviors
      may be amplified in tissue from patients with epilepsy, resulting in an increased
      propensity to generate seizures.

PMID- 21076321
TI  - Computational modeling of epileptic activity: from cortical sources to EEG
      signals.
AB  - In epileptic patients candidate to surgery, the interpretation of EEG signals
      recorded either within (depth EEG) or at the surface (scalp EEG) of the head is a
      crucial issue to determine epileptogenic brain regions and to define subsequent
      surgical strategy. This task remains difficult as there is no simple relationship
      between the spatiotemporal features of neuronal generators (convoluted cortical
      dipole layers) and the electric field potentials recorded by the electrodes.
      Indeed, this relationship depends on the complex interaction of several factors
      regarding involved cortical sources: location, area, geometry, and
      synchronization of neuronal activity. A computational model is proposed to
      address this issue. It relies on a neurophysiologically relevant model of EEG
      signals, which combines an accurate description of both the intracerebral sources
      of activity and the transfer function between dipole layers and recorded field
      potentials. The model is used, on the one hand, to quantitatively study the
      influence of source-related parameters on the properties of simulated signals,
      and on the other hand, to jointly analyze depth EEG and scalp EEG signals. In
      this article, the authors review some of the results obtained from the model with
      respect to the literature on the interpretation of EEG signals in the context of
      epilepsy.

PMID- 21076324
TI  - Comparing epileptiform behavior of mesoscale detailed models and population
      models of neocortex.
AB  - Two models of the neocortex are developed to study normal and pathologic neuronal
      activity. One model contains a detailed description of a neocortical microcolumn
      represented by 656 neurons, including superficial and deep pyramidal cells, four
      types of inhibitory neurons, and realistic synaptic contacts. Simulations show
      that neurons of a given type exhibit similar, synchronized behavior in this
      detailed model. This observation is captured by a population model that describes
      the activity of large neuronal populations with two differential equations with
      two delays. Both models appear to have similar sensitivity to variations of total
      network excitation. Analysis of the population model reveals the presence of
      multistability, which was also observed in various simulations of the detailed
      model.

PMID- 21076325
TI  - Interictal EEG discoordination in a rat seizure model.
AB  - Cognitive and psychiatric comorbidities are common and clinically important in
      medial temporal lobe epilepsy and are likely caused by ongoing abnormalities in
      brain activity. In addition, it is unclear how the dynamics of interictal brain
      activity in medial temporal lobe epilepsy contributes to the generation of
      seizures. To investigate these issues, the authors evaluated multisite interictal
      EEG from a perinatal excitotoxic, hippocampal lesion rat model of medial temporal
      lobe epilepsy. Sample entropy, an information theoretical measure, demonstrated
      decreased complexity at different time scales and across all channels in
      epileptic animals. However, higher-order multiarea measures showed evidence of
      increased variability in population correlation measures. This apparent paradox
      was resolved by noting that although the EEG from epileptic animals was overall
      more stereotyped, there were frequent periods where two or more brain areas
      "broke off" from ongoing brain activity in epileptic animals, producing
      decorrelations between areas. These decorrelations were particularly apparent
      across the midline, suggesting impairments of interhemispheric coordination, a
      form of interhemispheric diaschisis. Both the observed alterations could
      contribute to a reduction in brain functionality: an overall reduction in
      complexity and a failure of interhemispheric brain coordination, suggesting a
      breakdown in communication between hemispheres. The authors speculate that any
      tendency of areas to lose communication or break away from coordinated brain
      activity might predispose to seizures in these areas.

PMID- 21076326
TI  - EEG, temporal correlations, and avalanches.
AB  - Epileptiform activity in the EEG is frequently characterized by rhythmic,
      correlated patterns or synchronized bursts. Long-range temporal correlations
      (LRTC) are described by power law scaling of the autocorrelation function and
      have been observed in scalp and intracranial EEG recordings. Synchronous large
      amplitude bursts (also called neuronal avalanches) have been observed in local
      field potentials both in vitro and in vivo. This article explores the presence of
      neuronal avalanches in scalp and intracranial EEG in the context of LRTC. Results
      indicate that both scalp and intracranial EEG show LRTC, with larger scaling
      exponents in scalp recordings than intracranial. A subset of analyzed recordings
      also show avalanche behavior, indicating that avalanches may be associated with
      LRTC. Artificial test signals reveal a linear relationship between the scaling
      exponent measured by detrended fluctuation analysis and the exponent of the
      avalanche size distribution. Analysis and evaluation of simulated data reveal
      that preprocessing of EEG (squaring the signal or applying a filter) affect the
      ability of detrended fluctuation analysis to reliably measure LRTC.

PMID- 21076327
TI  - Aberrant neuronal avalanches in cortical tissue removed from juvenile epilepsy
      patients.
AB  - Some forms of epilepsy may arise as a result of pathologic interactions among
      neurons. Many forms of collective activity have been identified, including waves,
      spirals, oscillations, synchrony, and neuronal avalanches. All these emergent
      activity patterns have been hypothesized to show pathologic signatures associated
      with epilepsy. Here, the authors used 60-channel multielectrode arrays to record
      neuronal avalanches in cortical tissue removed from juvenile epilepsy patients.
      For comparison, they also recorded activity in rat cortical slices. The authors
      found that some human tissue removed from epilepsy patients exhibited prolonged
      periods of hyperactivity not seen in rat slices. In addition, they found a
      positive correlation between the branching parameter, a measure of network gain,
      and firing rate in human slices during periods of hyperactivity. This
      relationship was not present in rat slices. The authors suggest that this
      positive correlation between the branching parameter and the firing rate is part
      of a positive feedback loop and may contribute to some forms of epilepsy. These
      results also indicate that neuronal avalanches are abnormally regulated in slices
      removed from pediatric epilepsy patients.

PMID- 21076328
TI  - Automated analysis of EEG: opportunities and pitfalls.
AB  - Automated analysis is the transformation and representation of raw EEG data in an
      alternate form to allow clinicians to better or more quickly understand and
      interpret the data for diagnostic purposes. For the purposes of development,
      automated analysis encompasses everything from simple transforms such as the Fast
      Fourier Transform for isolating spectral components of EEG to full binary
      detectors. These analyses can help clinicians detect and diagnose clinical
      conditions such as seizures, traumatic brain injuries, and many other types of
      disease. In this article, opportunities and hazards will be examined as seen from
      the prospective of the automated analysis developer.

PMID- 21076329
TI  - Interictal spikes in psychiatric patients: a controversy in need for
      resurrection.

PMID- 21076330
TI  - Why the EEG should not be discounted.

PMID- 21076331
TI  - Systematic comparison of the behaviors produced by computational models of
      epileptic neocortex.
AB  - Two existing models of brain dynamics in epilepsy, one detailed (i.e., realistic)
      and one abstract (i.e., simplified) are compared in terms of behavioral range and
      match to in vitro mouse recordings. A new method is introduced for comparing
      across computational models that may have very different forms. First, high-level
      metrics were extracted from model and in vitro output time series. A principal
      components analysis was then performed over these metrics to obtain a reduced set
      of derived features. These features define a low-dimensional behavior space in
      which quantitative measures of behavioral range and degree of match to real data
      can be obtained. The detailed and abstract models and the mouse recordings
      overlapped considerably in behavior space. Both the range of behaviors and
      similarity to mouse data were similar between the detailed and abstract models.
      When no high-level metrics were used and principal components analysis was
      computed over raw time series, the models overlapped minimally with the mouse
      recordings. The method introduced here is suitable for comparing across different
      kinds of model data and across real brain recordings. It appears that, despite
      differences in form and computational expense, detailed and abstract models do
      not necessarily differ in their behaviors.

PMID- 21076332
TI  - Network variability across human tissue samples in vitro: the problem and a
      solution.
AB  - Slices prepared from cortical tissue that is surgically removed from patients to
      treat their epilepsy provide an opportunity to directly study the mechanisms
      underlying ictal activity. However, human in vitro studies have several
      limitations. One problem that may severely compromise investigations of network
      properties in these slices relates to how difficult it is to cut the tissue at
      angles that optimally preserve columnar connectivity. To address this problem,
      the authors investigated the degree of network variability in human tissue across
      samples and, within a single tissue sample, across slices cut at different angles
      using a novel form of optical imaging based on flavoprotein autofluorescence. The
      authors found a high degree of variability in the spatial extent, degree, and
      patterning of activation in slices from different samples. They also found
      variability across the slices cut from a single tissue sample at different
      angles. Indeed, these results suggest that human tissue samples have disparate
      degrees of network activity and that abnormal tissue may be confined to clusters
      of synchronously oscillating domains. Assessing circuit connectivity in a slice a
      priori will allow investigators to control for the overall degree of slice
      connectivity and selectively target active (or inactive) areas, making for better
      informed comparisons of data.

PMID- 21076334
TI  - Introducing songbirds as a model system for epilepsy research.
AB  - It has been broadly recognized that the avian forebrain shares extensive homology
      with neocortex, and the two share similar patterns of input, local circuit, and
      output connectivity. Some songbird species also exhibit a full range of vigilance
      states and ultradian patterns in gross (EEG) potentials that are commonly seen in
      mammals. The avian forebrain is organized in a field and nuclear fashion, giving
      great technical advantage especially when manipulating specialized regions such
      as forebrain song system nuclei associated with vocal learning that would be hard
      to achieve in cortex. Songbirds are a model system for studying developmental
      processes at multiple levels of analysis, including but not limited to
      mechanistic electrophysiological descriptions of vocal production and vocal
      learning process. Recent behavioral evidence establishes a role for sleep in the
      vocal learning process of birds. This is likely to be related to the observed
      neuronal replay during sleep in songbirds and its emergence at the onset of
      exposure to a song tutor and formation of an auditory memory. These features of
      birdsong learning and the song system position it as an attractive model system
      for systems-level epilepsy research, especially for pediatric epilepsies and for
      those that are expressed during sleep and affect language development.

PMID- 21076333
TI  - Interictal spikes precede ictal discharges in an organotypic hippocampal slice
      culture model of epileptogenesis.
AB  - In organotypic hippocampal slice cultures, principal neurons form aberrant
      excitatory connections with other principal cells in response to slicing induced
      deafferentation, similar to mechanisms underlying epileptogenesis in
      posttraumatic epilepsy. To investigate the consequences of this synaptogenesis,
      the authors recorded field-potential activity from area CA3 during perfusion with
      the complete growth medium used during incubation. At 7 days in vitro, slice
      cultures only displayed multiunit activity. At 14 days in vitro, the majority
      displayed population bursts reminiscent of interictal-like spikes, but sustained
      synchronous activity was rare. Band-pass filtering of interictal discharges
      revealed fast ripple-like complexes, similar to in vivo recordings. Spontaneous
      ictal-like activity became progressively more prevalent with age: at 21 days in
      vitro, 50% of organotypic hippocampal slice cultures displayed long-lasting,
      ictal-like discharges that could be suppressed by phenytoin, whereas interictal
      activity was not suppressed. The fraction of cultures displaying ictal events
      continually increased with incubation time. Quantification of population spike
      activity throughout epileptogenesis using automatic detection and clustering
      algorithms confirmed the appearance of interictal-like activity before ictal-like
      discharges and also revealed high-frequency pathologic multiunit activity in
      slice cultures at 14 to 17 days in vitro. These experiments indicate that
      interictal-like spikes precede the appearance of ictal-like activity in a reduced
      in vitro preparation. Epileptiform activity in cultures resembled in vivo
      epilepsy, including sensitivity to anticonvulsants and steadily increasing
      seizure incidence over time, although seizure frequency and rate of
      epileptogenesis were higher in vitro. Organotypic hippocampal slice cultures
      comprise a useful model system for investigating mechanisms of epileptogenesis as
      well as developing antiepileptic and antiepileptogenic drugs.

PMID- 21076336
TI  - Malformations of cortical development and aberrant cortical networks:
      epileptogenesis and functional organization.
AB  - Malformations of cortical development are a major cause of drug-resistant
      epilepsy. Focal cortical dysplasia, heterotopia, and polymicrogyria are often
      manifested as discrete areas of abnormal neuronal migration and improper
      development of the cerebral cortex. Some of the patients harboring these
      malformations have obvious neurologic impairment, but others show unexpected
      deficits that are detectable only by screening. The role of surgical treatment of
      epilepsy due to localized malformations of cortical development is now
      established. However, its technical application can be challenging in that
      localization of function based on anatomic landmarks may not be reliable.
      Intracranial recordings have shown a high propensity for complex epileptogenic
      networks that may include remote cortical and subcortical regions. The MRI
      visible area of cortical abnormality should therefore be regarded as just an
      indicator of the epileptogenic zone rather than its tangible substrate.
      Completeness of resection, after delineation of the ictal onset zone, a key
      factor for successful epilepsy surgery, may be particularly difficult, and
      invasive EEG monitoring is necessary in most patients. Neural plasticity issues
      are of primary importance to surgical planning as the possibility of removing
      eloquent cortex permits more complete procedures with potentially higher rates of
      success. However, the functional consequences of malformative lesions are still
      poorly understood; conservation of function in the dysplastic cortex, its
      atypical representation, and relocation outside the malformed area are all
      possible. Surgical planning for associated epilepsy should therefore be based on
      individual assessments of structural imaging and of the major functions relevant
      to the area in question in the individual patient.

PMID- 21076335
TI  - Neuronal bursting properties in focal and parafocal regions in pediatric
      neocortical epilepsy stratified by histology.
AB  - To test the hypothesis that focal and parafocal neocortical tissue from pediatric
      patients with intractable epilepsy exhibits cellular and synaptic differences,
      the authors characterized the propensity of these neurons to generate (a) voltage
      dependent bursting and (b) synaptically driven paroxysmal depolarization shifts.
      Neocortical slices were prepared from tissue resected from patients with
      intractable epilepsy. Multiunit network activity and simultaneous whole-cell
      patch recordings were made from neurons from three patient groups: (1) those with
      normal histology; (2) those with mild and severe cortical dysplasia; and (3)
      those with abnormal pathology but without cortical dysplasia. Seizure-like
      activity was characterized by population bursting with concomitant bursting in
      intracellularly recorded cortical neurons (n = 59). The authors found
      significantly more N-methyl-D-aspartic acid-driven voltage-dependent bursting
      neurons in focal versus parafocal tissue in patients with severe cortical
      dysplasia (P < 0.01). Occurrence of paroxysmal depolarization shifts and burst
      amplitude and burst duration were significantly related to tissue type: focal or
      parafocal (P < 0.05). The authors show that functional differences between focal
      and parafocal tissue in patients with severe cortical dysplasia exist. There are
      functional differences between patient groups with different histology, and
      bursting properties can be significantly associated with the distinction between
      focal and parafocal tissue.

PMID- 21076337
TI  - Stress and epilepsy: multiple models, multiple outcomes.
AB  - Human studies show a link between stress and epilepsy, with stress causing an
      increase in seizure frequency and severity in patients with epilepsy. Many
      different animal model systems have been used to better understand this
      connection and the possible mechanisms involved. This review highlights the
      results of such studies relating stress and seizure susceptibility, with a focus
      on the hypothalamic-pituitary-adrenal axis and its relationship to seizure
      generation. The effects of hypothalamic-pituitary-adrenal axis mediators, acute
      stress, chronic stress, and early life stress on the seizure phenotype are
      summarized. Results suggest that stress has both anticonvulsive and proconvulsive
      properties, depending on the animal strain and the stress/seizure induction
      paradigm used. Attempts to interpret the stress-epilepsy literature must take
      these variables into account. The growing availability of genetically modified
      mice that carry either human epilepsy mutations or mutations in stress pathway
      genes now provide the opportunity to examine the relationship between stress and
      epilepsy more directly.

PMID- 21076338
TI  - Propagation of epileptiform activity on a submillimeter scale.
AB  - Microseizures are highly focal low-frequency epileptiform-appearing events
      recorded from the neocortex of epilepsy patients. Because of their tiny, often
      submillimeter distribution, they may be regarded as a high-resolution window into
      the epileptic process, providing an excellent opportunity to study the fine
      temporal structure of their origin and spread. A 16 mm2 96-microelectrode array
      with 400-MUm interelectrode spacing was implanted in seven patients undergoing
      invasive EEG monitoring for medically refractory epilepsy. Seven microdischarge
      populations were tested for a substantial contribution by volume conduction to
      the observed waveform amplitudes. Single-unit activity was examined for specific
      evidence of neural activity at multiple sites within the microdischarge fields.
      We found that microdischarges appear to originate at a highly focal source
      location, likely within a single cortical macrocolumn, and spread to local and
      more distant sites via neural propagation.

PMID- 21076339
TI  - Etiopathogenesis of catatonia: generalizations and working hypotheses.
AB  - Catatonia has been rediscovered over the last 2 decades as a unique syndrome that
      consists of specific motor signs with a characteristic and uniform response to
      benzodiazepines and electroconvulsive therapy. Further inquiry into its
      developmental, environmental, psychological, and biological underpinnings is
      warranted. In this review, medical catatonia models of motor circuitry
      dysfunction, abnormal neurotransmitters, epilepsy, genetic risk factors,
      endocrine dysfunction, and immune abnormalities are discussed. Developmental,
      environmental, and psychological risk factors for catatonia are currently
      unknown. The following hypotheses need to be tested: neuroleptic malignant
      syndrome is a drug-induced form of malignant catatonia; Prader-Willi syndrome is
      a clinical GABAergic genetic-endocrine model of catatonia; Kleine-Levin syndrome
      represents a periodic form of adolescent catatonia; and anti-N-methyl-d-aspartate
      receptor encephalitis is an autoimmune type of catatonia.

PMID- 21076340
TI  - Guidance for clinical trials for children and adolescents with chronic hepatitis
      C.
AB  - Most children with chronic hepatitis C are infected vertically, have a low
      natural seroconversion rate, and carry a lifetime risk of cirrhosis and cancer.
      Affected children are usually asymptomatic, and histological findings are mild
      with a low risk of progression, although 5% develop significant liver disease in
      childhood.The use of combination treatment with pegylated interferon-alpha and
      ribavirin has changed the outcome and prognosis for this disease, with
      approximately 60% of children achieving sustained viral clearance. Combination
      therapy is not ideal for children because pegylated interferon is administered
      subcutaneously, impairs growth velocity, and both interferon and ribavirin have
      significant adverse effects that affect compliance. In addition, approximately
      50% of children infected with genotype 1 do not respond to therapy. Thus,
      additional treatment options are required including improvement in dosing,
      reduction in the length of treatment, and evaluation of new drugs, such as
      protease inhibitors, which could be more effective for patients infected with
      genotype 1.The primary goal of treatment is to eradicate the infection. The
      future clinical trial design should ensure that any new drugs demonstrate
      noninferiority to the present standard regimen in both children and adults. The
      measure for documenting substantial improvement above present therapy should be
      increased viral clearance rate or the same clearance rate, with a shorter
      duration of treatment and/or fewer adverse effects. We do not believe there is
      any need for a placebo arm because approved therapy is available and new
      treatments can be compared with present therapy.Safety measures should include
      the standard recommended laboratory investigations, growth parameters, quality-of
      life or psychological measures, and a requirement for long-term follow-up for up
      to 5 years.

PMID- 21076341
TI  - Pneumatosis intestinalis: a rare presentation of Crohn disease exacerbation.

PMID- 21076342
TI  - Bilateral septic arthritis of the hip with osteitis and psoas abcess in a 17-year
      old adolescent.
AB  - Septic arthritis remains an important and serious disease of the young because of
      its high potential to cause permanent sequelae. The hip is the most commonly
      involved joint in infants and in the young (35%). Most often, patients have a
      single joint involved. We report here a rare case of septic arthritis reaching
      both hips, shown by a severe septicemic shock and complicated unusually by a
      psoas abcess and osteitis in an immunocompetent adolescent.

PMID- 21076343
TI  - 18F-fluoride PET/CT for assessing bone involvement in prostate and breast
      cancers.
AB  - OBJECTIVE: To evaluate the accuracy of 18F-fluoride PET/computed tomography (CT)
      to detect bone metastases (BMs) in a breast and prostate cancer population, using
      magnetic resonance imaging (MRI) or thin-slice CT as a gold standard. METHODS: We
      have prospectively included 34 patients with breast (N=24) or prostate cancer
      (N=10) at high risk of BMs. Whole-body PET/CT (low-dose CT) and bone scintigraphy
      (BS) with single photon emission CT were obtained for all 34 patients and the
      results compared with a radiological gold standard. RESULTS: Out of the 386 foci
      detected by PET/CT, 219 (56.7%) could be verified by CT or MRI. Eighty-six
      additional foci were detected by BS (n=46) or seen only by CT (n=9), MRI (n=23),
      or both CT and MRI (n=8). The total number of verified lesions was therefore 274
      (58.1%), including 119 (43.4%) benign and 155 (56.6%) BM. The sensitivity,
      specificity, and accuracy of 18F-fluoride PET/CT were 76, 84.2, and 80%,
      respectively. For BS, they were 44.8, 79.2, and 60%, respectively. Sensitivity
      significantly decreased for the lytic lesions. The accuracy of PET/CT was
      significantly superior to BS for pelvic and lumbar lesions. PET/CT provided a
      correct diagnosis (M+/M0) in 32 of 33 patients (one false positive) compared with
      28 of 33 with BS (four false positive, one false positive). CONCLUSION: 18F
      fluoride PET/CT is significantly more accurate than BS for detecting BMs from
      breast and prostate cancers.

PMID- 21076344
TI  - 18F-FLT and 18F-FDG positron emission tomography for the imaging of advanced well
      differentiated gastro-entero-pancreatic endocrine tumours.
AB  - PURPOSE: Gastro-entero-pancreatic (GEP) endocrine tumours are a heterogenous
      group of tumours of variable localization and prognosis. It has been suggested
      that positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose
      (18F-FDG) may have a prognostic value and help to identify patients at risk of
      progression. [18F]fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) has been
      recently developed as a PET proliferation tracer. At present, there are no
      studies investigating its role in GEP. The aim of this prospective study was to
      assess the value of 18F-FLT-PET for the evaluation of GEP. MATERIALS AND METHODS:
      Ten patients with biopsy-proven locally advanced or metastasized, well
      differentiated GEP neuroendocrine tumours were prospectively enrolled and
      scheduled for 18F-FDG and 18F-FLT-PET. Images were compared with other
      conventional diagnostic procedures, namely computed tomography, ultrasound,
      somatostatin receptor scintigraphy and with clinical and diagnostic follow-up.
      RESULTS: Evaluation criteria were interpreted in terms of assumed presence of
      tumoral tissue. According to the patient's status, FDG was positive in five out
      of the seven patients with stable disease and in two out of the three patients
      with progressive disease. No positive case was identified by 18F-FLT in either
      the primary or the metastatic tumour site, whatever the status of patients, and
      this was probably a reflection of the slow proliferation rate of tumours.
      CONCLUSION: These preliminary data suggest that 18F-FLT-PET is not a suitable
      tracer for the evaluation of advanced well-differentiated GEP tumours. FDG showed
      good diagnostic performance but does not help to identify patients at risk of
      progression.

PMID- 21076345
TI  - Regional partition coefficient of water in patients with cerebrovascular disease
      and its effect on rCBF assessment.
AB  - OBJECTIVE: Cerebral blood flow (CBF) estimation with C15O2 PET usually assumes a
      single tissue compartment model and a fixed brain-blood partition coefficient of
      water. However, the partition coefficient may change in pathological conditions.
      The purpose of this study was to investigate the changes in the partition
      coefficient of water in pathological regions and its effect on regional CBF
      assessment. METHODS: The study protocol included 22 patients with occlusive
      cerebrovascular disease to compare the partition coefficients among three regions
      (infarction area, noninfarct hypoperfusion area, and contralateral area) in the
      pathological brain (analysis A), and to compare the CBF estimated by using a
      fixed partition coefficient and CBF estimated using floating partition
      coefficients (analysis B). RESULTS: The partition coefficient in the infarction
      area (0.55+/-0.07 ml/g) was lower than that in the contralateral normal cortex
      (0.68+/-0.05 ml/g), whereas noninfarct hypoperfusion area did not show a
      significant change (0.67+/-0.06 ml/g). As a result, the use of a fixed partition
      coefficient of normal volunteers (0.70 ml/g) resulted in an underestimation in
      regional CBF by 12% in infarction area (P<0.05), whereas the estimation errors
      were smaller and induced no significant difference in the noninfarct
      hypoperfusion area or in contralateral areas. CONCLUSION: The partition
      coefficient is stable except for the infarction area, and CBF estimation using a
      fixed partition coefficient of normal volunteers provides clinically appreciable
      information in patients with cerebrovascular disease.

PMID- 21076346
TI  - Preventing catheter-associated UTIs: survey report.

PMID- 21076347
TI  - Determining brain death: a review of evidence-based guidelines.

PMID- 21076349
TI  - Management of exercise-induced bronchospasm in adolescents with asthma.
AB  - Physical activity in persons with asthma is important at any age but even more so
      in adolescents. Collaboration between the nurse practitioner and adolescent is
      essential to develop an asthma management plan that will provide for optimal
      physical activity and prevent asthma exacerbations while exercising.

PMID- 21076350
TI  - Happy history-making holidays!

PMID- 21076351
TI  - Male infertility: A primer for NPs.
AB  - Few NPs are exposed to the topic of male infertility during the course of their
      training. There are medical and surgical treatment options for many of the most
      common diagnoses that contribute to decreased fertility in men. Recognizing these
      etiologies can help patients receive cost-effective treatment.

PMID- 21076352
TI  - A device for the relief of phantom limb pain and rehabilitation in stroke.
AB  - PURPOSE: To determine if simple, robust spectacle mounted devices are feasible
      for the replacement of the mirror boxes currently used in the rehabilitation of
      patients suffering from phantom limb pain, complex regional pain syndrome and
      stroke. METHODS: Four devices, using three different optical systems were
      produced: plane mirror, astronomical telescope using cylindrical lenses and two
      reflecting prism systems. RESULT: The illusory effect of the devices was similar
      to that of the mirror box. CONCLUSIONS: Any of the systems would be suitable to
      replace the mirror box, but the reflecting prism system is the easiest to set up.

PMID- 21076353
TI  - Visual field size criteria for mobility rehabilitation referral.
AB  - PURPOSE: To investigate evidence-based visual field size criteria for referral of
      low-vision (LV) patients for mobility rehabilitation. METHODS: One hundred and
      nine participants with LV and 41 age-matched participants with normal sight (NS)
      were recruited. The LV group was heterogeneous with diverse causes of visual
      impairment. We measured binocular kinetic visual fields with the Humphrey Field
      Analyzer and mobility performance on an obstacle-rich, indoor course. Mobility
      was assessed as percent preferred walking speed (PPWS) and number of obstacle
      contact errors. The weighted kappa coefficient of association (kappar) was used
      to discriminate LV participants with both unsafe and inefficient mobility from
      those with adequate mobility on the basis of their visual field size for the full
      sample and for subgroups according to type of visual field loss and whether or
      not the participants had previously received orientation and mobility training.
      RESULTS: LV participants with both PPWS <38% and errors >6 on our course were
      classified as having inadequate (inefficient and unsafe) mobility compared with
      NS participants. Mobility appeared to be first compromised when the visual field
      was less than about 1.2 steradians (sr; solid angle of a circular visual field of
      about 70 degrees  diameter). Visual fields <0.23 and 0.63 sr (31 to 52 degrees 
      diameter) discriminated patients with at-risk mobility for the full sample and
      across the two subgroups. A visual field of 0.05 sr (15 degrees  diameter)
      discriminated those with critical mobility. CONCLUSIONS: Our study suggests that:
      practitioners should be alert to potential mobility difficulties when the visual
      field is less than about 1.2 sr (70 degrees  diameter); assessment for mobility
      rehabilitation may be warranted when the visual field is constricted to about
      0.23 to 0.63 sr (31 to 52 degrees  diameter) depending on the nature of their
      visual field loss and previous history (at risk); and mobility rehabilitation
      should be conducted before the visual field is constricted to 0.05 sr (15 degrees
      diameter; critical).

PMID- 21076354
TI  - Impact of a rub and rinse on solution-induced corneal staining.
AB  - PURPOSE: To investigate whether the inclusion of a rub and rinse step before
      contact lens disinfection has an impact on solution-induced corneal staining.
      METHODS: This was a prospective, double-masked, single investigator study. Twenty
      participants were recruited for two visits, where balafilcon-A lenses were worn
      bilaterally for 2 h. Each pair of lenses was prepared using two different
      methodologies. The "control" lens was transferred from the blister pack directly
      into a storage case containing polyhexamethylene biguanide-based lens care
      solution. The contralateral "test" lens was rubbed and simultaneously rinsed
      using the same polyhexamethylene biguanide-based care solution, for either 60 s
      (visit 1) or 20 s (visit 2). Both lenses were then soaked in the solution
      overnight. After baseline corneal staining assessments, the lenses were inserted
      following a randomized contralateral model. After 2 h, lenses were removed,
      corneal staining was regraded, and comfort scores were obtained. RESULTS: Rubbed
      and rinsed test lenses induced significantly less corneal staining than control
      lenses for all participants during visit 1 (mean +/- SD: 516 +/- 843 vs. 2170 +/-
      902; p < 0.001) and visit 2 (522 +/- 417 vs. 2091 +/- 965; p < 0.001). There was
      no significant difference between the test lenses during visits 1 and 2 (p =
      0.72) or controls (p = 0.50). Comfort scores did not differ between eyes (p >
      0.05). CONCLUSIONS: Corneal staining induced after 2 h of lens wear with the
      combination of balafilcon-A and polyhexamethylene biguanide-based lens care
      solution can be significantly reduced by including a rub and rinse step before
      overnight soaking. Further work is required to establish the longevity of this
      effect during the monthly wearing cycle.

PMID- 21076355
TI  - Temporal stability in the perception of dry eye ocular discomfort symptoms.
AB  - PURPOSE: A prospective longitudinal study was designed to investigate the ability
      of patients with tear deficiency to correctly recall their past symptoms. The
      ultimate goal of the study was to contribute to the ongoing research concerning
      the lack of association between dry eye symptomatology and clinical tests of tear
      film evaluation. METHODS: A total of 26 subjects with ages ranging from 29 to 61
      years participated in the study. All subjects reported symptoms associated with
      tear deficiency, although none had been diagnosed with dry eye disease. Subjects
      were instructed to grade their symptoms on two different occasions, at the
      precise moment they were experiencing them, by means of a home questionnaire, and
      through a recall questionnaire, which was administered within a maximum interval
      of 10 days from the first questionnaire. Tear evaluation tests were performed at
      this second time. Non-parametric statistical analyses were used to investigate
      the relationship between present and recalled symptoms and between symptoms and
      signs, as well as between the different dry eye tests. The contributions of age,
      gender, and recall period were also evaluated. RESULTS: With the exception of
      irritation (p = 0.029) and scratchiness (p = 0.025), no statistically significant
      difference was encountered between home and recall questionnaires, although
      females were found to recall their symptoms slightly better than males (p =
      0.048). An increase in the severity of the symptoms was associated with a better
      recollection (p = 0.007). Symptoms (home or recalled) and clinical signs were not
      correlated, although the recalled symptom of scratchiness presented moderately
      strong correlations with several dry eye tests. CONCLUSIONS: Although the lack of
      correlation between dry eye tests and symptoms mirrored previous research,
      symptoms recall was found to follow certain interesting patterns, similar to
      those published in pain research literature.

PMID- 21076356
TI  - Reported wearing compliance of ready-made spectacles at 6 and 12 months.
AB  - PURPOSE: Ready-made spectacles are often used in low-resource environments, but
      to date, there has been little evaluation of the continued use of these
      spectacles over time. The aim of this study was to assess wearing compliance of
      those who received ready-made spectacles. METHODS: The International Rescue
      Committee trains refugee health workers to provide simple refractive services and
      dispense ready-made spherical lenses to residents of refugee camps on the
      Thailand-Burma border. We conducted follow-up interviews in five camps among all
      eligible and available spectacle recipients who had been examined either 6 (n =
      230) or 12 months earlier (n = 187). Interviewers asked about continued use of
      spectacles and, among those who had discontinued spectacle use, asked the reason
      for discontinuing. RESULTS: Reported spectacle wear was significantly higher at 6
      months compared with 12 months (73.9 vs. 55.6%, p < 0.001). At 6 months, wearing
      compliance was significantly higher for females than males (79.2 vs. 67.6%, p =
      0.033), but gender differences in wearing compliance were not seen at 12 months,
      and no differences were found between 10-year age groups at 6 or 12 months.
      Wearing compliance rates among recipients seen at different camps were
      significantly different at both 6 months (range, 58.1 to 87.5%, p = 0.005) and 12
      months (range, 32 to 85.7%, p = 0.002). The top reason given for discontinued
      spectacle wear was broken frames, followed by vision-related complaints,
      scratched lenses, lost spectacles, and appearance. CONCLUSIONS: Our findings
      suggest that spectacle wearing compliance studies will not be comparable unless a
      standard time frame is used to assess compliance. We found assessing self
      reported compliance to be a useful tool in guiding our program. Understanding the
      reasons for non-compliance will help guide corrective action and planning of
      interventions designed to increase wearing rates.

PMID- 21076357
TI  - Paraxial ocular rotation with astigmatic lenses.
AB  - PURPOSE: To obtain analytical formulas for calculating the ocular rotation and
      the prismatic effect with a general lens, centered or decentered, with particular
      reference to thick spherotoric spectacle lenses. METHODS: Linear theory is used,
      using the symplectic properties of optical matrices, to derive the desired
      formulas. RESULTS: By applying the general formulas to particular cases, the
      corresponding formulas are obtained, sometimes recovering formulas already known.
      Two examples serve to illustrate the use of the formulas obtained and to compare
      the results they provide with the ones obtained by exact ray tracing.
      CONCLUSIONS: The linear formulas derived allow to find, in a rather easy way,
      quite accurate values of the ocular rotation and the prismatic effect in the
      paraxial region.

PMID- 21076358
TI  - Reliability of a computer-aided manual procedure for segmenting optical coherence
      tomography scans.
AB  - PURPOSE: To assess the within- and between-operator agreement of a computer-aided
      manual segmentation procedure for frequency-domain optical coherence tomography
      scans. METHODS: Four individuals (segmenters) used a computer-aided manual
      procedure to mark the borders defining the layers analyzed in glaucoma studies.
      After training, they segmented two sets of scans, an Assessment Set and a Test
      Set. Each set had scans from 10 patients with glaucoma and 10 healthy controls.
      Based on an analysis of the Assessment Set, a set of guidelines was written. The
      Test Set was segmented twice with a >=1 month separation. Various measures were
      used to compare test and retest (within-segmenter) variability and between
      segmenter variability including concordance correlations between layer borders
      and the mean across scans (n = 20) of the mean of absolute differences between
      local border locations of individual scans, MEAN{mean( DeltaLBL )}. RESULTS:
      Within-segmenter reliability was good. The mean concordance correlations values
      for an individual segmenter and a particular border ranged from 0.999 +/- 0.000
      to 0.978 +/- 0.084. The MEAN{mean( DeltaLBL )} values ranged from 1.6 to 4.7 MUm
      depending on border and segmenter. Similarly, between-segmenter agreement was
      good. The mean concordance correlations values for an individual segmenter and a
      particular border ranged from 0.999 +/- 0.001 to 0.992 +/- 0.023. The MEAN{mean(
      DeltaLBL )} values ranged from 1.9 to 4.0 MUm depending on border and segmenter.
      The signed and unsigned average positions were considerably smaller than the
      MEAN{mean( DeltaLBL )} values for both within- and between-segmenter comparisons.
      Measures of within-segmenter variability were only slightly larger than those of
      between-segmenter variability. CONCLUSIONS: When human segmenters are trained,
      the within-and between-segmenter reliability of manual border segmentation is
      quite good. When expressed as a percentage of retinal layer thickness, the
      results suggest that manual segmentation provides a reliable measure of the
      thickness of layers typically measured in studies of glaucoma.

PMID- 21076359
TI  - Brain-derived neurotrophic factor as a biomarker in primary open-angle glaucoma.
AB  - PURPOSE: To introduce a novel biomarker for screening of primary open-angle
      glaucoma (POAG) by detecting and measuring brain-derived neurotrophic factor
      (BDNF) in the serum of normal subjects and patients with early stage of glaucoma.
      METHODS: Twenty-five glaucoma patients as the case group and 25 age- and sex
      matched normal persons as the control group were tested. The control group
      comprised 19 men and 6 women, with the mean age of 59.32 +/- 11.8 years and
      without any apparent ocular or systemic diseases. The case group comprised 20 men
      and 5 women, with the mean age of 59.64 +/- 11.56 years, who were assessed by
      routinely performed clinical and paraclinical investigations. BDNF levels in
      serum were determined by enzyme-linked immunosorbent assay using monoclonal
      antibodies specific for BDNF. RESULTS: The mean of BDNF levels in the serum was
      27.16 +/- 5.53 ng/mL in the control subjects and 18.42 +/- 4.05 ng/mL in the
      subjects with the early stage glaucoma. A statistically significant difference
      was evident between the two groups (p < 0.05). We found no significant
      differences in serum BDNF levels according to the subjects' age, gender, duration
      of the glaucoma, mean intraocular pressure, and blood pressure (p > 0.05).
      Glaucoma patients who had lower serum BDNF concentration had disclosed a
      significant negative correlation with pattern standard deviations. CONCLUSIONS:
      We conclude that BDNF in the serum might be a useful biochemical marker for early
      detection of POAG. We also propose that this might be a reliable, time efficient,
      and cost-effective method for diagnosis, screening, and assessing the progression
      of POAG. However, more studies and trials are needed to investigate these factors
      in greater detail.

PMID- 21076360
TI  - Cost-effectiveness of glaucoma interventions in Barbados and Ghana.
AB  - PURPOSE: More than 90% of blindness worldwide exists in the developing world, but
      information on the social and economic burden and the cost-effectiveness of
      treatment in these settings is often limited or nonexistent. We demonstrate the
      use of computer modeling to simulate the current and future epidemiology,
      outcomes, and treatment of primary open-angle glaucoma in high-incidence
      populations of the developing world. METHODS: A previously validated vision model
      was modified to simulate the incidence progression and social and economic
      outcomes of glaucoma in Barbados, which was the source of epidemiology data, and
      Ghana, which has similar propensity for glaucoma but lower socioeconomic
      development. We then assessed the cost-effectiveness of hypothetical case-finding
      and treatment scenarios, including U.S. guideline-level care and one-time laser
      surgery. RESULTS: Barbados incurs relatively greater social and economic burden
      from glaucoma than Ghana. In Barbados, population screening followed by U.S.
      guideline levels of care appears to be highly cost-effective. Because of a
      younger population with higher mortality at younger ages, glaucoma appears to
      cause less visual impairment and blindness in Ghana than in Barbados, resulting
      in lower per capita disability and productivity losses. Population screening or
      guideline-level treatment scenarios were generally not cost-effective in Ghana,
      but treating self-referring patients with a hypothetical one-time laser surgery
      was highly cost-effective relative to World Health Organization willingness to
      pay thresholds. CONCLUSIONS: The social and economic burden of glaucoma is higher
      in developed nations because of increased life expectancy, an older population
      age profile, and higher per capita gross domestic product. Similarly, lower
      mortality rates and higher per capita gross domestic product increase the
      relative cost-effectiveness of screening and treatment interventions intended to
      mitigate glaucoma burden.

PMID- 21076361
TI  - A trial of methadone tapering schedules in pediatric intensive care unit patients
      exposed to prolonged sedative infusions.
AB  - OBJECTIVES: To compare the efficacy of a low-dose methadone tapering schedule to
      a high-dose methadone tapering schedule in pediatric intensive care unit patients
      exposed to infusions of fentanyl, with or without infusions of midazolam, for >=
      5 days. DESIGN: Prospective, double-blind, randomized trial. SETTING: Pediatric
      intensive care unit in a tertiary care children's hospital. PATIENTS: Seventy
      eight patients, 74 of whom had been receiving infusions of both fentanyl and
      midazolam, were randomized. Forty-one patients were randomized to the low-dose
      methadone group and 37 were randomized to the high-dose methadone group. Sixty
      patients successfully completed the trial, 34 were in the low-dose methadone
      group, and 26 were in the high-dose methadone group. INTERVENTIONS: Patients were
      randomized to receive methadone either at a starting dose of 0.1 mg/kg/dose (low
      dose methadone group) or at a starting dose based on both the patient's weight
      and the most recent fentanyl infusion rate (high-dose methadone group). In each
      group, methadone was administered every 6 hrs for the first 24 hrs and then every
      12 hrs for the second 24 hrs. The methadone was then decreased to once daily and
      tapered off over the next 10 days. Patients were monitored for withdrawal
      symptoms using the Modified Narcotic Withdrawal Score. MEASUREMENTS AND MAIN
      RESULTS: The percentage of patients who successfully completed the 10-day
      methadone taper was the same in the low-dose methadone group as in the high-dose
      methadone group (56% vs. 62%; p = .79). Patients that failed to complete the
      assigned methadone taper had a greater total fentanyl dose and longer pediatric
      intensive care unit length of stay compared to patients who completed the
      assigned methadone taper. CONCLUSIONS: Patients who received infusions of
      fentanyl for at least 5 days were just as likely to complete a low-dose methadone
      taper as a high-dose methadone taper. Because of the risks of both withdrawal and
      oversedation with any fixed methadone schedule, the methadone dose must be
      adjusted according to each patient's response.

PMID- 21076362
TI  - The role of chest radiographs and tuberculin skin tests in tuberculosis screening
      of internationally adopted children.
AB  - BACKGROUND: Internationally adopted children (IAC) are a growing group of US
      immigrants who often come from countries with high tuberculosis (TB) burdens.
      There is limited evidence to support current TB screening guidelines in these
      high-risk children. Therefore, we have prospectively examined the clinical
      utility of tuberculin skin testing (TST) and subsequent chest radiograph
      screening for TB disease in recently immigrated, asymptomatic IAC. METHODS:
      Within 6 months of immigration to the United States, we collected demographic
      information and assessed the nutritional status of 566 IAC who presented for
      routine postadoptive care. Children completed standardized clinical examination
      and TSTs. Chest radiographs were recommended for children with TST induration >=
      5 mm. The association between TST induration and clinical outcome was assessed.
      The clinical utility of chest radiographs was evaluated. RESULTS: There was no
      difference in age, birth country, or nutritional status between IAC with TST
      induration of 0 to < 5 mm and those with 5 to < 10 mm; IAC with TST >= 10 mm were
      older, more chronically malnourished, and more likely to emigrate from Guatemala.
      Among children with TST >= 5 mm (35%), 4 IAC had chest radiographs which were
      initially interpreted to be abnormal and consistent with TB; ultimately none were
      diagnosed with TB. CONCLUSIONS: The 5-mm TST cut point did not capture IAC with
      risk factors for latent TB infection or progression to TB disease, suggesting
      that this is not a useful screening threshold. In contrast, a 10-mm cut point
      identified IAC at risk for TB infection and therefore should be a more useful
      screening threshold. We question the clinical utility of radiographic screening
      for pulmonary TB in asymptomatic children.

PMID- 21076363
TI  - Achalasia and mycobacterium goodii pulmonary infection.
AB  - Achalasia is a common adult disorder that rarely manifests in children and
      infrequently can be associated with pulmonary nontuberculous mycobacteria
      infections. We describe here the first case of Mycobacterium goodii pulmonary
      infection associated with achalasia in a pediatric patient. Heller myotomy with
      Dor fundoplication and 12 months of treatment with ciprofloxacin and doxycycline
      resulted in complete clinical and radiologic improvement.

PMID- 21076364
TI  - Complete atrioventricular block as a complication of varicella in children.
AB  - Although varicella is a benign and self-limited disease in children, serious
      complications can occur. We herein report a case of a 15-month-old boy who
      required a permanent pacemaker because of complete atrioventricular block as a
      complication of varicella. Universal vaccination is warranted to prevent such a
      potentially fatal complication in Japan where varicella is still endemic.

PMID- 21076365
TI  - The remaining challenge of pneumonia: the leading killer of children.

PMID- 21076366
TI  - Obesity in pregnancy: implications for the mother and lifelong health of the
      child. A consensus statement.
AB  - Obesity among pregnant women is becoming one of the most important women's health
      issues. Obesity is associated with increased risk of almost all pregnancy
      complications: gestational hypertension, preeclampsia, gestational diabetes
      mellitus, delivery of large-for-GA infants, and higher incidence of congenital
      defects all occur more frequently than in women with a normal BMI. Evidence shows
      that a child of an obese mother may suffer from exposure to a suboptimal in utero
      environment and that early life adversities may extend into adulthood. In
      September 2009, ILSI Europe convened a workshop with multidisciplinary expertise
      to review practices and science base of health and nutrition of obese pregnant
      women, with focus on the long-term health of the child. The consensus viewpoint
      of the workshop identified gaps and gave recommendations for future research on
      gestational weight gain, gestational diabetes, and research methodologies. The
      evidence available on short- and long-term health impact for mother and child
      currently favors actions directed at controlling prepregnancy weight and
      preventing obesity in women of reproductive ages. More randomized controlled
      trials are needed to evaluate the effects of nutritional and behavioral
      interventions in pregnancy outcomes. Moreover, suggestions that maternal obesity
      may transfer obesity risk to child through non-Mendelian (e.g. epigenetic)
      mechanisms require more long-term investigation.

PMID- 21076368
TI  - Effects of IL-13 on mucociliary differentiation of pediatric asthmatic bronchial
      epithelial cells.
AB  - Goblet cell hyperplasia (GCH) and decreased ciliated cells are characteristic of
      asthma. We examined the effects of IL-13 (2 and 20 ng/mL) on in vitro mucociliary
      differentiation in pediatric bronchial epithelial cells (PBECs) of normal PBEC
      [PBEC(N)] and asthmatic PBEC [PBEC(A)] children. Markers of differentiation, real
      time PCR for MUC5AC, MUC5AC ELISA, and transepithelial electrical resistance
      (TEER) were assessed. Stimulation with 20 ng/mL IL-13 in PBEC(N) resulted in GCH
      [20 ng/mL IL-13: mean, 33.8% (SD, 7.2) versus unstimulated: mean, 18.9% (SD,
      5.0); p < 0.0001] and decreased ciliated cell number [20 ng/mL IL-13: mean, 8%
      (SD, 5.6) versus unstimulated: mean, 22.7% (SD,7.6); p < 0.01]. PBEC(N)
      stimulated with 20 ng/mL IL-13 resulted in >5-fold (SD, 3.2) increase in MUC5AC
      mRNA expression, p < 0.001, compared with unstimulated PBEC(N). In PBEC(A), GCH
      was also seen [20 ng/mL IL-13: mean, 44.7% (SD, 16.4) versus unstimulated: mean,
      30.4% (SD, 13.9); p < 0.05] with a decreased ciliated cell number [20 ng/mL IL
      13: mean, 8.8% (SD, 7.5) versus unstimulated: mean, 16.3% (SD, 4.2); p < 0.001].
      We also observed an increase in MUC5AC mRNA expression with 20 ng/mL IL-13 in
      PBEC(A), p < 0.05. IL-13 drives PBEC(N) toward an asthmatic phenotype and worsens
      the phenotype in PBEC(A) with reduced ciliated cell numbers and increased goblet
      cells.

PMID- 21076367
TI  - Pneumococcal peptidoglycan-polysaccharides regulate Toll-like receptor 2 in the
      mouse middle ear epithelial cells.
AB  - Toll-like receptor 2 (TLR2) plays a key role in the host defense against Gram
      staining positive (Gram) bacteria and their cell wall envelope components.
      However, little is known about the expression of TLR2 in the middle ear under
      otitis media (OM) conditions, and its role in the persistent otitis media with
      effusion (OME). In this study, we demonstrated that the pneumococcal cell wall
      component, peptidoglycan-polysaccharides (PGPS), activated the expression of TLR2
      in the middle ear epithelial cells through the nuclear factor kappa B (NF-kappaB)
      cytokine signaling pathway while I kappa B alpha mutant (IkappaBalphaM), a
      dominant negative inhibitor of NF-kappaB, abrogated the expression of TLR2
      induced by PGPS. This study suggests that the existence of residual PGPS may
      maintain a low profile of cytokine production in the middle ear mucosa and thus
      contribute to the pathogenesis of OME.

PMID- 21076369
TI  - Mouse hind limb transplantation: a new composite tissue allotransplantation model
      using nonsuture supermicrosurgery.
AB  - BACKGROUND: The development of microsurgical techniques has facilitated the
      establishment of vascularized composite tissue transplant models in small
      mammals. Because the mouse would be the ideal model to study various composite
      tissue allotransplantation (CTA)-related problems, we designed two new surgical
      techniques for orthotopic (ORT) and heterotopic (HET) hind limb transplantation.
      METHODS: BALB/c hind limbs were transplanted to BALB/c or C57BL6 recipients using
      a nonsuture cuff technique. ORT: donor femoral vessels were anastomosed to
      recipient femoral vessels, the sciatic nerve approximated end-to-end and
      osteosynthesis was performed using an intramedullary rod. HET/cervical: Donor
      femoral vessels of a reduced size osteomyocutaneous hind limb CTA were
      anastomosed to recipient common carotid artery and external jugular vein without
      nerve approximation. RESULTS: Both procedures could be performed with a high
      success rate (ORT: 62%; HET: 90%). Donor operation lasted for 100+/-12 min and
      recipient operation 114+/-27 min (ORT) and 54+/-16 min (HET). Complication rates
      in terms of bleeding, and thrombosis at the cuff side was slightly higher in the
      ORT group. All syngeneic grafts survived long term (>100 days). FK506 (2 mg/kg)
      significantly prolonged graft survival (87+/-22 days) when compared with
      untreated controls (6+/-1 day). Functional evaluation of ORT grafts by means of
      video gait kinematics and CatWalk analysis revealed specific differences of gait
      parameters when compared with nontransplanted controls (P<0.05). CONCLUSIONS: The
      ORT hind limb transplant model seems to be best suited to study functional
      outcome and nerve regeneration in CTA. The technically less demanding
      HET/cervical model may be used to investigate basic immunology and clinically
      relevant questions related to acute and chronic rejection, and ischemia
      reperfusion injury in reconstructive transplantation.

PMID- 21076370
TI  - Induction of kidney allograft tolerance by soluble CD83 associated with
      prevalence of tolerogenic dendritic cells and indoleamine 2,3-dioxygenase.
AB  - BACKGROUND: Tolerogenic dendritic cells (Tol-DCs) play a critical role in
      inducing and maintaining tolerance. Recognizing that both T-cell inactivation and
      activation are contingent on signals provided by DCs and that graft-specific
      activated T cells are major mediators of transplant rejection, we aimed to create
      an environment favoring Tol-DCs with a novel reagent, human soluble CD83
      (hsCD83). METHODS: Life-supporting orthotopic kidney transplantation was
      performed in a C57BL/6-to-BALB/c mouse model. The study group was treated with
      hsCD83 (100 MUg/mouse/day, postoperative days -1 to +7, intravenously) and
      compared with untreated controls. RESULTS: Treatment with hsCD83 achieved kidney
      allograft tolerance (>100 days), with negligible antidonor antibody detected. In
      contrast, kidney grafts in untreated recipients demonstrated severe rejection
      after 35 days, characterized by cellular infiltration, interstitial hemorrhage
      and edema, and glomerular and tubular necrosis, as well as high antidonor
      antibody titers. In addition, splenic DCs of tolerant recipients exhibited
      significantly decreased levels of surface major histocompatibility complex class
      II, CD40, CD80, and intracellular interleukin-12, as well as reduced allogeneic
      stimulatory capacity. Adoptive transfer of CD11c+ DCs from tolerant hsCD83
      treated animals induced kidney allograft tolerance in syngeneic recipients.
      Blocking indoleamine 2,3-dioxygenase with 1-methyl-tryptophan (15 mg/mouse/day;
      gavage) prevented the immunosuppressive effect of hsCD83, abrogating hsCD83
      induced Tol-DCs and graft tolerance, and leading to acute kidney graft rejection
      in 22 days. CONCLUSION: hsCD83 alone was capable of inducing kidney allograft
      tolerance through a mechanism involving Tol-DC generation and, at least in part,
      indoleamine 2,3-dioxygenase activity. Because sCD83 is of human origin, the
      therapeutic approach used in our mouse transplant model holds significant promise
      for clinical transplantation.

PMID- 21076371
TI  - Whole blood biomarkers of acute cardiac allograft rejection: double-crossing the
      biopsy.
AB  - BACKGROUND: Acute rejection is still a significant barrier to long-term survival
      of the allograft. Current acute rejection diagnostic methods are not specific
      enough or are invasive. There have been a number of studies that have explored
      the blood or the biopsy to discover genomic biomarkers of acute rejection;
      however, none of the studies to date have used both. METHODS: We analyzed
      endomyocardial biopsy tissue and whole blood-derived messenger RNA from 11 acute
      rejection and 20 nonrejection patients using Affymetrix Human Genome U133 Plus
      2.0 chips. We used a novel approach and gained insight into the biology of
      rejection based on gene expression in the biopsy, and applied this knowledge to
      the blood analysis to identify novel blood biomarkers. RESULTS: We identified
      probesets that are differentially expressed between acute rejection and
      nonrejection patients in the biopsy and blood, and developed three biomarker
      panels: (1) based on biopsy-only (area under the curve=0.85), (2) based on biopsy
      targeted whole blood (area under the curve=0.83), and (3) based on whole blood
      only (area under the curve=0.60) analyses. CONCLUSIONS: Most of the probesets
      replicated between biopsy and blood are regulated in opposite direction between
      the two sources of information. We also observed that the biopsy-targeted blood
      biomarker discovery approach can improve performance of the biomarker panel. The
      biomarker panel developed using this targeted approach is able to diagnose acute
      cardiac allograft rejection almost as well as the biopsy-only based biomarker
      panel.

PMID- 21076372
TI  - Ganciclovir pharmacokinetic parameters do not change when extending
      valganciclovir cytomegalovirus prophylaxis from 100 to 200 days.
AB  - BACKGROUND: A 3-month course of prophylaxis is usually recommended for
      cytomegalovirus (CMV) D+/R- renal transplant recipients. Based on recent data, up
      to 6 months of prophylaxis may be used. A subanalysis was performed to evaluate
      the pharmacokinetics of ganciclovir after valganciclovir administration and to
      perform an exploratory pharmacokinetic/pharmacodynamic analysis. METHODS: In
      Improved Protection Against Cytomegalovirus in Transplant, a phase III,
      randomized, double blind, placebo-controlled, multicenter study, 318 CMV D+/R-
      kidney transplant recipients received valganciclovir prophylaxis (900 mg once
      daily) for 200 or 100 days. A population pharmacokinetic analysis was conducted
      on a subgroup of patients (n=120). The relationships between ganciclovir exposure
      (AUC0-24 hr) and clinical outcomes were explored. RESULTS: The final population
      parameter estimates (95% confidence interval) were as follows: apparent clearance
      of ganciclovir, 12 L/hr (11.3-12.7 L/hr); volume of distribution, 18.5 L (14.4
      22.6 L); and peripheral volume, 44.4 L (40.2-48.6 L). No differences were
      apparent between the two treatment groups and these estimates. These results are
      consistent with previously published pharmacokinetic models. There were no direct
      correlations between the likelihood of developing hematologic adverse events and
      ganciclovir exposure at the time of the event. The incidence of CMV disease was
      not correlated with ganciclovir exposure. CONCLUSION: The pharmacokinetics of
      ganciclovir were similar between the two dosing groups (100 vs. 200 days), with
      the majority of patients achieving an area under the concentration time curve in
      the target therapeutic range (40-60 MUg hr/mL). The fact that the majority of
      patients were within the target therapeutic range and the absence of a control
      arm (no treatment) precluded any attempt to validate a correlation with clinical
      parameters (i.e., CMV disease).

PMID- 21076373
TI  - Customized mycophenolate dosing based on measuring inosine-monophosphate
      dehydrogenase activity significantly improves patients' outcomes after renal
      transplantation.
AB  - BACKGROUND: Significant relationships have been reported between the uptake of
      mycophenolic acid (MPA) and the risk of acute rejection. In a prospective study
      after renal transplantation, we assessed the value of measuring inosine
      monophosphate dehydrogenase (IMPDH) activity as a predictive indicator of an
      acute rejection episode in the initial postoperative period. PATIENTS AND
      METHODS: Fifty-two patients received 360 mg enteric-coated mycophenolate-sodium
      two times per day with concomitant tacrolimus/cyclosporine A, providing a total
      of 122 pharmacodynamic profiles. IMPDH activity was measured by a validated high
      performance liquid chromatography method in four plasma samples collected at
      predose, 30 and 60 min, 2 and 4 hr, and preoperative, during weeks 1 and 2 and 3
      months after transplantation. MPA concentrations were measured by mass
      spectrometry. Inhibition of IMPDH was correlated to the MPA values, MPA area
      under the curves, and predose levels of the different calcineurin inhibitors.
      RESULTS: Comparing the two groups (group I: rejection; n=17; mean age 51+/-15
      years vs. group II: no rejection; n=35; mean age 51+/-14 years), we found a
      significantly (P<0.001) lower inhibition of IMPDH in group I (26.5%+/-11% vs.
      56.7%+/-18%) already in the first week after transplantation. There was no
      correlation of MPA values (6.85+/-4 vs. 4.1+/-3 mg/L; first week) nor with the
      calcineurin inhibitor trough blood levels. Area under the curves for MPA did not
      differ significantly. Furthermore, IMPDH activity was a reliable predictor of
      rejection episodes and inflammation. CONCLUSION: The data suggest that measuring
      biologic response may be a more valuable indicator than traditional therapeutic
      drug monitoring of MPA. Patients at risk for rejection could be earlier
      identified, and the therapeutic potential of MPA will be optimized.

PMID- 21076374
TI  - Fenoldopam preconditioning: role of heme oxygenase-1 in protecting human tubular
      cells and rodent kidneys against cold-hypoxic injury.
AB  - BACKGROUND: Kidneys from brain-dead donors are cold preserved until transplanted.
      However, prolonged cold storage can contribute to allograft failure. Studies
      suggest that donor preconditioning with dopaminergics may reduce cold-ischemic
      transplant injury, but whether heme oxygenase (HO)-1 induction is an underlying
      mechanism is not known. OBJECTIVE: To test whether preconditioning with
      fenoldopam (FD) induce HO-1 and protect kidneys against cold storage injury and
      whether HO-1 plays a role in protection. METHOD: We used human renal proximal
      tubular epithelial cells, rat kidney transplants, and HO-1 null mice kidneys.
      RESULTS: FD preconditioning of cells for 4 hr significantly protected against
      cell death from 24-hr cold hypoxia and was associated with a dose-dependent
      increase in HO-1 expression. In a syngeneic rat kidney transplant model, FD
      preconditioning for 18 hr markedly increased kidney HO-1 expression and protected
      kidneys against 24-hr cold-ischemic transplant injury. To test the role of HO-1,
      renal proximal tubular epithelial cells were treated with HO-1 small interfering
      RNA, followed by FD-preconditioning. Small interfering RNA inhibited the HO-1
      messenger RNA expression and reversed the FD protection. Suspension of kidneys of
      HO-1 null and wild-type mice preconditioned with FD or saline were subjected to
      24- and 48-hr cold storage. N-acetyl glucosaminidase, a specific tubular injury
      marker, was significantly lower in FD-preconditioned wild-type kidneys, but not
      in HO-1 null kidneys, suggesting a role for HO-1 in FD's preconditioning.
      CONCLUSION: Our data suggest HO-1 induction as an underlying mechanism for FD
      preconditioning and support the idea of testing FD preconditioning in the
      clinical setting. Studies are required to determine the optimum FD
      preconditioning protocol.

PMID- 21076375
TI  - 24 weeks of valganciclovir prophylaxis in children after renal transplantation: a
      4-year experience.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection
      after solid-organ transplant. Valganciclovir prophylaxis significantly reduces
      disease, but limited data are available on its use in children. Recently, an
      increase in delayed-onset CMV disease has been noted with some arguing that
      longer prophylaxis may decrease late-onset disease. METHODS: Single-center,
      retrospective analysis of pediatric renal transplant patients receiving 24 weeks
      valganciclovir prophylaxis (15 mg/kg/day, maximum 900 mg/day) from January 2004
      to December 2008, aiming to measure the incidence of CMV disease and toxicity of
      valganciclovir. RESULTS: We enrolled 111 patients, 60% males, 46% African
      Americans, and median age at transplant 14.5 years (range 1.4-20.4 years). Sixty
      nine percent of donors and 44% of recipients were seropositive pretransplant.
      Median duration of valganciclovir use was 5.9 months (range 0.5-24 months). CMV
      viremia and disease occurred in 27% and 4.5%, respectively. All patients with
      disease presented after prophylaxis ended and all were D+/R-. Thymoglobulin use
      (P = 0.04) and positive donor CMV status (P = 0.02) were associated with a higher
      risk of CMV viremia. Twenty-four percent had hematologic toxicity directly
      associated with valganciclovir. CONCLUSIONS: Valganciclovir use in children was
      effective as prophylaxis against CMV disease; no children at our institution
      developed disease while on therapy. Our regimen of 24 weeks of prophylaxis was
      associated with a lower rate of late-onset disease than previous reports with 12
      week regimens. Further controlled studies should be considered to compare longer
      versus shorter periods of prophylaxis and dose reductions and their impact on
      prevention of late-onset disease, resistance, cost, and toxicity.

PMID- 21076376
TI  - Graft-versus-host disease after intestinal and multivisceral transplantation.
AB  - BACKGROUND: Graft-versus-host-disease (GVHD) is a rare complication but carries a
      high mortality after transplantation. We retrospectively evaluated the incidence,
      risk factors and impact of this complication on the survival outcome of
      intestinal transplantation at a single center. METHODS: 241 patients who
      underwent intestinal transplantation between March 1994 and July 2007 were
      analyzed for evidence of GVHD. A diagnosis of GVHD was based on clinical
      presentations and confirmed by histological findings. RESULTS: Of the 241
      patients, 22 (9.1%) were diagnosed as GVHD. The median time of GVHD onset was 75
      days (range, 14-1,408). The incidence of GVHD was significantly higher in young
      children than in adults (13.2 versus 4.4%, P = 0.05). The multivisceral graft
      recipients were more likely to develop GVHD compared with those of isolated small
      bowel (12.4% versus 4.6%, P = 0.05). The presence of recipient splenectomy was
      significantly associated with the incidence of GVHD (P = 0.03). The inclusion of
      the spleen in the multivisceral grafts tended to be at an increased risk of GVHD
      compared with the group without the spleen transplant (12.3% versus 7.9%, P =
      0.43). A total of 16 patients with GVHD died during the entire follow-up.
      Infection was the leading cause of death in 55% patients. CONCLUSIONS: GVHD is a
      fatal and progressive complication of small bowel transplantation. Younger
      children, multivisceral graft recipients, and particularly those with splenectomy
      are at high risk of developing GVHD after transplantation.

PMID- 21076377
TI  - Pretransplant kidney-specific treatment to eliminate the need for systemic
      immunosuppression.
AB  - BACKGROUND: Despite significant side effects, chronic systemic immunosuppression
      remains the backbone of clinical transplantation. We investigated the feasibility
      of preventing early allorecognition in canine renal allografts using a
      nonsystemic pretreatment. METHODS: The renal vasculature was treated with a
      bioengineered interface consisting of a nano-barrier membrane during 3 hr of ex
      vivo warm perfusion. RESULTS: Preliminary feasibility of the immunocloaking
      technology was established by the following criteria: it is possible to achieve
      approximately 90% coverage of the vasculature with nano-barrier membrane after 3
      hr of ex vivo warm perfusion; covering the luminal surfaces prevents
      allorecognition as determined by mixed lymphocyte-vascular endothelial reaction;
      covering the luminal surfaces does not negatively affect renal function as
      determined by autotransplant outcomes; and graft rejection is significantly
      postponed in canine kidneys treated with the immunocloaking technology. In the
      absence of systemic immunosuppression, untreated control dogs experienced a mean
      onset of rejection on day 6, whereas in the treated dogs with modified renal
      vascular luminal surfaces, the mean onset of rejection was significantly delayed
      until day 30. CONCLUSIONS: The ability to postpone, or eventually eliminate, the
      allorecognition that occurs immediately on reperfusion could provide a new window
      of opportunity to introduce adjunct therapies to support tolerance induction. To
      our knowledge, this is the first time significantly prolonged canine renal
      allograft survival has been achieved in the absence of systemic immunosuppression
      or immunologic manipulation of the recipient.

PMID- 21076378
TI  - Cytomegalovirus prevention and long-term recipient and graft survival in
      pediatric heart transplant recipients.
AB  - INTRODUCTION: The association between cytomegalovirus (CMV) immune globulin
      (CMVIG) and clinical outcomes in pediatric heart transplantation has not been
      evaluated. Long-term recipient and graft survival were compared between pediatric
      heart recipients who received CMV prophylaxis with CMVIG (with or without
      antivirals), antivirals without CMVIG, and no prophylaxis. CMVIG (with or without
      antivirals) versus no prophylaxis was also assessed in the CMV-positive donor/CMV
      negative recipient cohort. METHODS: Data from the Scientific Registry of
      Transplant Recipients included patients with a transplant date between January
      1995 and October 2008; follow-up data were through March 2009. All pediatric
      (younger than 18 years) recipients of primary, single-organ heart transplants
      were included. Kaplan-Meier analysis was used to examine rates of recipient death
      and graft loss at 7 years posttransplantation. Cox proportional hazards
      regression was used to estimate adjusted risk for graft loss and death. RESULTS:
      CMVIG (with or without antivirals) and antivirals without CMVIG were both
      associated with significantly (P<=0.05) lower rates of graft loss and death
      versus no prophylaxis. After adjustment, CMVIG was associated with a
      significantly decreased adjusted risk for graft loss and a borderline (P=0.09)
      decreased adjusted mortality risk; antiviral prophylaxis was associated with
      decreased adjusted risk for graft loss and mortality. In the CMV-positive
      donor/CMV-negative recipient cohort, CMVIG (with or without antivirals) was
      associated with decreased adjusted risk for graft loss and death. CONCLUSIONS:
      CMV prophylaxis with CMVIG or antivirals seems to offer long-term clinical
      outcome benefits. Determination of optimal regimen, dosage, and duration remains
      to be examined.

PMID- 21076379
TI  - Combined transplantation of pancreatic islets and adipose tissue-derived stem
      cells enhances the survival and insulin function of islet grafts in diabetic
      mice.
AB  - BACKGROUND: Overcoming significant loss of transplanted islet mass is important
      for successful islet transplantation. Adipose tissue-derived stem cells (ADSCs)
      seem to have angiogenic potential and antiinflammatory properties. We
      hypothesized that the inclusion of ADSCs with islet transplantation should
      enhance the survival and insulin function of the islet graft. METHODS: Syngeneic
      ADSCs and allogeneic islets were transplanted simultaneously under the kidney
      capsules of diabetic C57BL/6J mice. Rejection of the graft was examined by
      measurement of blood glucose level. Revascularization and inflammatory cell
      infiltration were examined by immunohistochemistry. RESULTS: Transplantation of
      400 islets only achieved normoglycemia with graft survival of 13.6+/-1.67 days
      (mean+/-standard deviation), whereas that of 100 or 200 allogeneic islets never
      reversed diabetes. Transplantation of 200 islets with 2*10(5) ADSCs reversed
      diabetes and significantly prolonged graft survival (13.0+/-5.48 days). Results
      of glucose tolerance tests performed on day 7 were significantly better in islets
      ADSCs than islets-alone recipients. Immunohistochemical analysis confirmed the
      presence of insulin-stained islet grafts with well-preserved structure in islets
      ADSCs transplant group. Significant revascularization (larger number of von
      Willebrand factor-positive cells) and marked inhibition of inflammatory cell
      infiltration, including CD4+ and CD8+ T cells and macrophages, were noted in the
      islets-ADSCs transplant group than islets-alone transplant group. CONCLUSIONS:
      Our results indicated that cotransplantation of ADSCs with islet graft promoted
      survival and insulin function of the graft and reduced the islet mass required
      for reversal of diabetes. This innovative protocol may allow "one donor to one
      recipient" islet transplantation.

PMID- 21076380
TI  - Mechanism analysis of long-term graft survival by monocarboxylate transporter-1
      inhibition.
AB  - BACKGROUND: Monocarboxylate transporter (MCT)-1, a member of a family of
      molecules, transports monocarboxylates such as lactate. Inhibiting MCT-1 leads to
      long-term graft survival in rodent heart transplantation and induces tolerance.
      We evaluated an MCT-1 inhibitor, AS2495674, in a rat heart transplant model and
      analyzed its underlying mechanism. METHODS: AS2495674 was tested on rat
      lymphocytes to determine its effect on lactate accumulation, proliferation, and
      immunoglobulin production. The effect of AS2495674 on graft survival was tested
      on the Brown Norway to Lewis rat strain combination with a second heart
      transplantation to test donor-specific suppression. Histology and ex vivo
      analyses were done to examine the AS2495674 effects on the immune response.
      RESULTS: In vitro, AS2495674 resulted in lactate accumulation, inhibited
      lymphocyte proliferation, and prevented immunoglobulin production. AS2495674
      induced long-term allograft survival with little evidence of chronic rejection
      and induced donor-specific suppression. Evaluation of the allograft and
      peripheral T lymphocytes from the AS2495674 group compared with that of vehicle
      showed (1) decreased donor-specific T lymphocyte response, (2) more forkhead box
      P3+ (Foxp3+) and CD45RA+ cells in the allograft, (3) higher gene expression of
      chemokines and chemokine receptors in the allograft, and (4) preferential
      inhibition of Foxp3(-) cells with little or no effect on Foxp3+ cells.
      CONCLUSIONS: AS2495674 prevents acute rejection, reduces features of chronic
      rejection, and induces tolerance. Our data suggest that the mechanism of
      AS2495674 involves generating a tolerogenic graft environment by preferentially
      targeting T effector cells while sparing the generation of T regulatory cells.

PMID- 21076381
TI  - Belatacept-based regimens versus a cyclosporine A-based regimen in kidney
      transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies.
AB  - BACKGROUND: At 1 year, belatacept was associated with similar patient/graft
      survival, better renal function, and an improved cardiovascular/metabolic risk
      profile versus cyclosporine A (CsA) in the Belatacept Evaluation of
      Nephroprotection and Efficacy as Firstline Immunosuppression Trial (BENEFIT) and
      Belatacept Evaluation of Nephroprotection and Efficacy as Firstline
      Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT) studies. Acute
      rejection was more frequent with belatacept in BENEFIT. Posttransplant
      lymphoproliferative disorder (PTLD)--specifically central nervous system PTLD-
      was observed more frequently in belatacept-treated patients. This analysis
      assesses outcomes from BENEFIT and BENEFIT-EXT after 2 years of treatment.
      METHODS: Patients received a more intensive (MI) or a less intensive (LI) regimen
      of belatacept or a CsA-based regimen. RESULTS: Four hundred ninety-three of 666
      patients (74%) in BENEFIT and 347 of 543 (64%) in BENEFIT-EXT completed 2 years
      of treatment. The proportion of patients who survived with a functioning graft
      was similar across groups (BENEFIT: 94% MI, 95% LI, and 91% CsA; BENEFIT-EXT: 83%
      MI, 84% LI, and 83% CsA). Belatacept's renal benefits were sustained, as
      evidenced by a 16 to 17 mL/min (BENEFIT) and an 8 to 10 mL/min (BENEFIT-EXT)
      higher calculated glomerular filtration rate in the belatacept groups versus CsA.
      There were few new acute rejection episodes in either study between years 1 and
      2. Because PTLD risk was highest in Epstein-Barr virus (EBV) (-) patients, an
      efficacy analysis of EBV (+) patients was performed and was consistent with the
      overall population results. There were two previously reported cases of PTLD in
      each study between years 1 and 2 in the belatacept groups. The overall balance of
      safety and efficacy favored the LI over the MI regimen. CONCLUSIONS: At 2 years,
      belatacept-based regimens sustained better renal function, similar patient/graft
      survival, and an improved cardiovascular/metabolic risk profile versus CsA;
      outcomes that were maintained in EBV (+) patients. No new safety signals emerged.

PMID- 21076382
TI  - Beneficial effects of perioperative low-dose inhaled carbon monoxide on pulmonary
      allograft survival in MHC-inbred CLAWN miniature swine.
AB  - BACKGROUND: We have recently reported that perioperative low-dose carbon monoxide
      (CO) inhalation decreases lung ischemia-reperfusion injury in miniature swine.
      The aims of this study were to establish a large animal model of pulmonary
      allograft rejection using polymerase chain reaction-typed major
      histocompatibility complex (MHC)-inbred CLAWN miniature swine and to examine the
      effects of CO on allograft survival. METHODS: Eleven CLAWN miniature swines
      received fully MHC-mismatched lungs followed by 12 days of tacrolimus (days 0-11;
      blood level 35-45 ng/mL). Six recipients received tacrolimus alone (control
      group). Five recipients were additionally treated with inhaled CO (180 min for
      donors until graft harvest; 390 min for recipients until 2 hr after reperfusion).
      RESULTS: All recipients treated with tacrolimus alone uniformly rejected their
      grafts by postoperative day 63 with development of cytotoxic antidonor
      antibodies. CO treatment was effective in prolonging allograft survival from a
      mean of 47+/-7 to 82+/-13 days (P=0.017), with one CO-treated animal maintaining
      function until postoperative day 120. Development of antidonor antibodies and
      donor-specific responsiveness by cell-mediated lympholysis and mixed lymphocyte
      reaction assays was delayed in animals that received CO therapy. Furthermore,
      serum concentrations of proinflammatory cytokines (interleukin-1beta and -6) 1
      day after transplant were significantly decreased in the CO-treated group.
      CONCLUSIONS: Fully MHC-mismatched lungs in CLAWN miniature swine were
      consistently rejected within 63 days, suggesting that this is a robust large
      animal model ideal for investigating mechanisms and treatment of lung rejection.
      Perioperative low-dose CO inhalation prolonged graft survival and inhibited
      antidonor antibody production and was associated with decreased proinflammatory
      mediators in this model.

PMID- 21076383
TI  - Patient survival after the diagnosis of cancer in renal transplant recipients: a
      nested case-control study.
AB  - INTRODUCTION: Malignancy is a well-known complication after renal
      transplantation. We studied the influence of cancer on patient survival in the
      Dutch renal transplant population in a nested case-controlled analysis. METHODS:
      Between March 1966 and May 2008, 15,227 renal transplantations in 12,805
      recipients were registered in the Netherlands Organ Transplant Registry database.
      Total follow-up was 89,651 person years. We performed an analysis of patient and
      graft survival both from the day of transplantation and the diagnosis of cancer
      in recipients with invasive cancer. Recipients without invasive cancer, matched
      for gender, age, and year of transplantation, served as a control group. For the
      survival analysis after the diagnosis of cancer, the matched control group
      consisted of patients with a functioning graft at the moment the index patient
      was diagnosed with cancer. RESULTS: Cancer had been registered in 908 (7.1%)
      patients, 630 (69%) of them died with functioning kidney, 510 (81%) because of
      their malignancy (at 8.2 years after transplantation, median). The median patient
      survival after transplantation was 11.9 vs. 16.8 years in the study and control
      group, respectively (P<0.001). The median patient and graft survival after the
      diagnosis of cancer was 2.1 vs. 8.3 (P<0.001) and 25 vs. 22.4 (P<0.001) years in
      the study and control group, respectively. CONCLUSION: Mortality because of
      cancer is observed at a significantly later time after transplantation compared
      with mortality because of the other main lethal complications. It significantly
      affects life expectancy and carries a poor prognosis with a limited survival
      after diagnosis.

PMID- 21076384
TI  - CYP3A5 *1 allele: impacts on early acute rejection and graft function in
      tacrolimus-based renal transplant recipients.
AB  - BACKGROUND: Tacrolimus is a major immunosuppressant, which has a narrow
      therapeutic range and wide interindividual variation. The effects of genetic
      polymorphisms of cytochrome P450 3A (CYP3A) 5 and Adenosine triphosphate-binding
      cassette subfamily B member 1 (ABCB1) genes on the achievement of target
      tacrolimus trough levels and clinical outcomes in renal transplants were
      evaluated. METHODS: A total of 62 patients participated in this prospective
      study. After an initial fixed oral dose (0.08 mg/kg two times per day),
      tacrolimus doses were adjusted to a target range based on daily measurement of
      blood trough concentration. Every patient underwent 10-day scheduled biopsy. Both
      the patients and investigators were blinded for the genetic polymorphisms.
      RESULTS: Those subjects expressing CYP3A5 (n=29) evidenced significantly lower
      tacrolimus trough levels between days 1 and 5 after transplantation, when
      compared with nonexpressers (n=33). Significantly higher overall incidences of
      early T-cell-mediated rejection (TCR) of at least Banff grade 1 in severity
      (P=0.017), including clinical rejection within 10 days and subclinical rejection
      in biopsies at postoperative day 10 were detected in CYP3A5 expressers. The
      severity of TCR according to Banff '07 classification was associated with CYP3A5
      genotypes (P=0.012). Moreover, multivariate analysis identified CYP3A5 expression
      as an independent risk factor for TCR (odds ratio: 2.79; P=0.043). Significantly
      lower estimated glomerular filtration rates until 1 month and numerically lower
      estimated glomerular filtration rates by 12 months were noted in the CYP3A5
      expressers. The genetic polymorphisms of the ABCB1 genes exerted no significant
      effects. CONCLUSION: We confirmed the significant effects of CYP3A5 polymorphism
      on the achievement of target tacrolimus trough levels and the development of
      acute rejection in early period after transplantation and consequent renal
      allograft function.

PMID- 21076386
TI  - Chemical constituents of the bark of Dipteryx alata vogel, an active species
      against Bothrops jararacussu venom.
AB  - The effect of four sub-extracts prepared from the lyophilized hydroalcoholic bark
      of Dipteryx alata (Leguminosae-Papilionoideae) dissolved in a methanol-water
      (80:20) mixture through a liquid-liquid partition procedure has been investigated
      against the neuromuscular blockade of the venom of the snake Bothrops
      jararacussu. The active CH2Cl2 sub-extract has been extensively analyzed for its
      chemical constituents, resulting in the isolation of four lupane-type
      triterpenoids: lupeol, lupenone, 28-hydroxylup-20(29)-en-3-one, betulin, nine
      isoflavonoids: 8-O-methylretusin, 7-hydroxy-5,6,4'-trimethoxyisoflavone,
      afrormosin, 7-hydroxy-8,3',4'-trimethoxyisoflavone, 7,3'-dihydroxy-8,4'
      dimethoxyisoflavone, odoratin, 7,8,3'-trihydroxy-4'-methoxyisoflavone, 7,8,3'
      trihydroxy-6,4'-dimethoxyisoflavone, dipteryxin, one chalcone: isoliquiritigenin,
      one aurone: sulfuretin and three phenolic compounds: vanillic acid, vanillin, and
      protocatechuic acid. Their chemical structures were elucidated on the basis of
      spectroscopic analysis, including HRMS, 1D- and 2D-NMR techniques.

PMID- 21076385
TI  - Analysis of protein pathway networks using hybrid properties.
AB  - Given a protein-forming system, i.e., a system consisting of certain number of
      different proteins, can it form a biologically meaningful pathway? This is a
      fundamental problem in systems biology and proteomics. During the past decade, a
      vast amount of information on different organisms, at both the genetic and
      metabolic levels, has been accumulated and systematically stored in various
      specific databases, such as KEGG, ENZYME, BRENDA, EcoCyc and MetaCyc. These data
      have made it feasible to address such an essential problem. In this paper, we
      have analyzed known regulatory pathways in humans by extracting different
      (biological and graphic) features from each of the 17,069 protein-formed systems,
      of which 169 are positive pathways, i.e., known regulatory pathways taken from
      KEGG; while 16,900 were negative, i.e., not formed as a biologically meaningful
      pathway. Each of these protein-forming systems was represented by 352 features,
      of which 88 are graph features and 264 biological features. To analyze these
      features, the "Minimum Redundancy Maximum Relevance" and the "Incremental Feature
      Selection" techniques were utilized to select a set of 22 optimal features to
      query whether a protein-forming system is able to form a biologically meaningful
      pathway or not. It was found through cross-validation that the overall success
      rate thus obtained in identifying the positive pathways was 79.88%. It is
      anticipated that, this novel approach and encouraging result, although
      preliminary yet, may stimulate extensive investigations into this important
      topic.

PMID- 21076387
TI  - A highly efficient bismuth salts-catalyzed route for the synthesis of alpha
      aminophosphonates.
AB  - A convenient synthesis of different types of alpha-amino phosphonates via one-pot
      solvent-free three component reactions of aldehydes, amines and phosphites
      catalyzed by bismuth salts has been investigated. Bismuth triflate is found to be
      the most effective catalyst for this reaction.

PMID- 21076388
TI  - Crucial role of selenium in the virucidal activity of benzisoselenazol-3(2H)-ones
      and related diselenides.
AB  - Various N-substituted benzisoselenazol-3(2H)-ones and their non-selenium
      containing analogues have been synthesized and tested against selected viruses
      (HHV-1, EMCV and VSV) to determine the extent to which selenium plays a role in
      antiviral activity. The data presented here show that the presence of selenium is
      crucial for the antiviral properties of benzisoselenazol-3(2H)-ones since their
      isostructural analogues having different groups but lacking selenium either did
      not show any antiviral activity or their activity was substantially lower. The
      open-chain analogues of benzisoselenazol-3(2H)-ones--diselenides also exhibited
      high antiviral activity while selenides and disulfides were completely inactive
      towards model viruses.

PMID- 21076389
TI  - Study on suitability of KOD DNA polymerase for enzymatic production of artificial
      nucleic acids using base/sugar modified nucleoside triphosphates.
AB  - Recently, KOD and its related DNA polymerases have been used for preparing
      various modified nucleic acids, including not only base-modified nucleic acids,
      but also sugar-modified ones, such as bridged/locked nucleic acid (BNA/LNA) which
      would be promising candidates for nucleic acid drugs. However, thus far, reasons
      for the effectiveness of KOD DNA polymerase for such purposes have not been
      clearly elucidated. Therefore, using mutated KOD DNA polymerases, we studied here
      their catalytic properties upon enzymatic incorporation of nucleotide analogues
      with base/sugar modifications. Experimental data indicate that their
      characteristic kinetic properties enabled incorporation of various modified
      nucleotides. Among those KOD mutants, one achieved efficient successive
      incorporation of bridged nucleotides with a 2'-ONHCH2CH2-4' linkage. In this
      study, the characteristic kinetic properties of KOD DNA polymerase for modified
      nucleoside triphosphates were shown, and the effectiveness of genetic engineering
      in improvement of the enzyme for modified nucleotide polymerization has been
      demonstrated.

PMID- 21076390
TI  - Phenolic compounds from Merremia umbellata subsp. orientalis and their
      allelopathic effects on Arabidopsis seed germination.
AB  - A bioassay-directed phytochemical study was carried out to investigate potential
      allelochemicals of the invasive plant Merremia umbellata subsp. orientalis (Hall.
      f.). Eight phenolic compounds, including a salicylic acid (SA)-derived new
      natural product, SA 2-O-beta-D-(3',6'-dicaffeoyl)-glucopyranoside (1), and seven
      known ones 2-8 were isolated and identified from two bioactive sub-fractions of
      the acetone extract of this plant. The structure of new compound 1 was
      established by spectral and chemical methods. The potential allelopathic effects
      of these compounds at 0.5 and 1.0 mM concentrations on the germination of
      Arabidopsis seeds were tested. Results showed that 2 remarkably inhibited seed
      germination at concentrations as low as 0.5 mM. Compound 3 only moderately
      inhibited seed germination at 0.5 mM, but displayed strong inhibitory bioactivity
      at 1.0 mM concentration. Compounds 4 and 5 showed only slight inhibitory
      bioactivity at 1.0 mM, while the other compounds showed no obvious inhibitory
      effects.

PMID- 21076391
TI  - Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function
      in Wnt-producing cells.
AB  - Wnt proteins are lipid-modified glycoproteins that have important roles in
      development, adult tissue homeostasis and disease. Secretion of Wnt proteins from
      producing cells is mediated by the Wnt-binding protein MIG-14/Wls, which binds
      Wnt in the Golgi network and transports it to the cell surface for release. It
      has recently been shown that recycling of MIG-14/Wls from the plasma membrane to
      the trans-Golgi network is required for efficient Wnt secretion, but the
      mechanism of this retrograde transport pathway is still poorly understood. In
      this study, we report the identification of MTM-6 and MTM-9 as novel regulators
      of MIG-14/Wls trafficking in Caenorhabditis elegans. MTM-6 and MTM-9 are
      myotubularin lipid phosphatases that function as a complex to dephosphorylate
      phosphatidylinositol-3-phosphate, a central regulator of endosomal trafficking.
      We show that mutation of mtm-6 or mtm-9 leads to defects in several Wnt-dependent
      processes and demonstrate that MTM-6 is required in Wnt-producing cells as part
      of the MIG-14/Wls-recycling pathway. This function is evolutionarily conserved,
      as the MTM-6 orthologue DMtm6 is required for Wls stability and Wg secretion in
      Drosophila. We conclude that regulation of endosomal trafficking by the MTM-6/MTM
      9 myotubularin complex is required for the retromer-dependent recycling of MIG
      14/Wls and Wnt secretion.

PMID- 21076392
TI  - The tumour suppressor C/EBPdelta inhibits FBXW7 expression and promotes mammary
      tumour metastasis.
AB  - Inflammation and hypoxia are known to promote the metastatic progression of
      tumours. The CCAAT/enhancer-binding protein-delta (C/EBPdelta, CEBPD) is an
      inflammatory response gene and candidate tumour suppressor, but its physiological
      role in tumourigenesis in vivo is unknown. Here, we demonstrate a tumour
      suppressor function of C/EBPdelta using transgenic mice overexpressing the
      Neu/Her2/ERBB2 proto-oncogene in the mammary gland. Unexpectedly, this study also
      revealed that C/EBPdelta is necessary for efficient tumour metastasis. We show
      that C/EBPdelta is induced by hypoxia in tumours in vivo and in breast tumour
      cells in vitro, and that C/EBPdelta-deficient cells exhibit reduced glycolytic
      metabolism and cell viability under hypoxia. C/EBPdelta supports CXCR4
      expression. On the other hand, C/EBPdelta directly inhibits expression of the
      tumour suppressor F-box and WD repeat-domain containing 7 gene (FBXW7, FBW7, AGO,
      Cdc4), encoding an F-box protein that promotes degradation of the mammalian
      target of rapamycin (mTOR). Consequently, C/EBPdelta enhances mTOR/AKT/S6K1
      signalling and augments translation and activity of hypoxia-inducible factor
      1alpha (HIF-1alpha), which is necessary for hypoxia adaptation. This work
      provides new insight into the mechanisms by which metastasis-promoting signals
      are induced specifically under hypoxia.

PMID- 21076393
TI  - Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal
      condensation products in mouse eyes.
AB  - Multiphoton excitation fluorescence microscopy (MPM) can image certain molecular
      processes in vivo. In the eye, fluorescent retinyl esters in subcellular
      structures called retinosomes mediate regeneration of the visual chromophore, 11
      cis-retinal, by the visual cycle. But harmful fluorescent condensation products
      of retinoids also occur in the retina. We report that in wild-type mice,
      excitation with a wavelength of ~730 nm identified retinosomes in the retinal
      pigment epithelium, and excitation with a wavelength of ~910 nm revealed at least
      one additional retinal fluorophore. The latter fluorescence was absent in eyes of
      genetically modified mice lacking a functional visual cycle, but accentuated in
      eyes of older wild-type mice and mice with defective clearance of all-trans
      retinal, an intermediate in the visual cycle. MPM, a noninvasive imaging modality
      that facilitates concurrent monitoring of retinosomes along with potentially
      harmful products in aging eyes, has the potential to detect early molecular
      changes due to age-related macular degeneration and other defects in retinoid
      metabolism.

PMID- 21076394
TI  - Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of
      the cornea.
AB  - Basal tearing is crucial to maintaining ocular surface wetness. Corneal cold
      thermoreceptors sense small oscillations in ambient temperature and change their
      discharge accordingly. Deletion of the cold-transducing ion channel Transient
      receptor potential cation channel subfamily M member 8 (TRPM8) in mice abrogates
      cold responsiveness and reduces basal tearing without affecting nociceptor
      mediated irritative tearing. Warming of the cornea in humans also decreases
      tearing rate. These findings indicate that TRPM8-dependent impulse activity in
      corneal cold receptors contributes to regulating basal tear flow.

PMID- 21076395
TI  - Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog
      Gli pathway.
AB  - Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis. To
      investigate the mechanism by which glioma-associated oncogene family zinc finger
      1 (GLI1), a crucial effector of Hh signaling, regulates Hh pathway activation, we
      searched for GLI1-interacting proteins. We report that the chromatin remodeling
      protein SNF5 (encoded by SMARCB1, hereafter called SNF5), which is inactivated in
      human malignant rhabdoid tumors (MRTs), interacts with GLI1. We show that Snf5
      localizes to Gli1-regulated promoters and that loss of Snf5 leads to activation
      of the Hh-Gli pathway. Conversely, re-expression of SNF5 in MRT cells represses
      GLI1. Consistent with this, we show the presence of a Hh-Gli-activated gene
      expression profile in primary MRTs and show that GLI1 drives the growth of SNF5
      deficient MRT cells in vitro and in vivo. Therefore, our studies reveal that SNF5
      is a key mediator of Hh signaling and that aberrant activation of GLI1 is a
      previously undescribed targetable mechanism contributing to the growth of MRT
      cells.

PMID- 21076396
TI  - Interdependence of behavioural variability and response to small stimuli in
      bacteria.
AB  - The chemotaxis signalling network in Escherichia coli that controls the
      locomotion of bacteria is a classic model system for signal transduction. This
      pathway modulates the behaviour of flagellar motors to propel bacteria towards
      sources of chemical attractants. Although this system relaxes to a steady state
      in response to environmental changes, the signalling events within the chemotaxis
      network are noisy and cause large temporal variations of the motor behaviour even
      in the absence of stimulus. That the same signalling network governs both
      behavioural variability and cellular response raises the question of whether
      these two traits are independent. Here, we experimentally establish a fluctuation
      response relationship in the chemotaxis system of living bacteria. Using this
      relationship, we demonstrate the possibility of inferring the cellular response
      from the behavioural variability measured before stimulus. In monitoring the pre-
      and post-stimulus switching behaviour of individual bacterial motors, we found
      that variability scales linearly with the response time for different functioning
      states of the cell. This study highlights that the fundamental relationship
      between fluctuation and response is not constrained to physical systems at
      thermodynamic equilibrium but is extensible to living cells. Such a relationship
      not only implies that behavioural variability and cellular response can be
      coupled traits, but it also provides a general framework within which we can
      examine how the selection of a network design shapes this interdependence.

PMID- 21076397
TI  - Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA.
AB  - Ribonuclease (RNase) P is the universal ribozyme responsible for 5'-end tRNA
      processing. We report the crystal structure of the Thermotoga maritima RNase P
      holoenzyme in complex with tRNA(Phe). The 154 kDa complex consists of a large
      catalytic RNA (P RNA), a small protein cofactor and a mature tRNA. The structure
      shows that RNA-RNA recognition occurs through shape complementarity, specific
      intermolecular contacts and base-pairing interactions. Soaks with a pre-tRNA 5'
      leader sequence with and without metal help to identify the 5' substrate path and
      potential catalytic metal ions. The protein binds on top of a universally
      conserved structural module in P RNA and interacts with the leader, but not with
      the mature tRNA. The active site is composed of phosphate backbone moieties, a
      universally conserved uridine nucleobase, and at least two catalytically
      important metal ions. The active site structure and conserved RNase P-tRNA
      contacts suggest a universal mechanism of catalysis by RNase P.

PMID- 21076398
TI  - Cardiac glycosides are potent inhibitors of interferon-beta gene expression.
AB  - Here we report that bufalin and other cardiac glycoside inhibitors of the sodium
      potassium ATPase (sodium pump) potently inhibit the induction of the interferon
      beta (IFNbeta) gene by virus, double-stranded RNA or double-stranded DNA. Cardiac
      glycosides increase the intracellular sodium concentration, which appears to
      inhibit the ATPase activity of the RNA sensor RIG-I, an essential and early
      component in the IFNbeta activation pathway. This, in turn, prevents the
      activation of the critical transcription factors IRF3 and NFkappaB. Bufalin
      inhibition can be overcome by expressing a drug-resistant variant of the sodium
      pump and knocking down the pump by short hairpin RNA inhibits IFNbeta expression.
      Thus, bufalin acts exclusively through the sodium pump. We also show that bufalin
      inhibits tumor necrosis factor (TNF) signaling, at least in part by interfering
      with the nuclear translocation of NFkappaB. These findings suggest that bufalin
      could be used to treat inflammatory and autoimmune diseases in which IFN or TNF
      are hyperactivated.

PMID- 21076399
TI  - Structural characterization of a misfolded intermediate populated during the
      folding process of a PDZ domain.
AB  - Incorrectly folded states transiently populated during the protein folding
      process are potentially prone to aggregation and have been implicated in a range
      of misfolding disorders that include Alzheimer's and Parkinson's diseases.
      Despite their importance, however, the structures of these states and the
      mechanism of their formation have largely escaped detailed characterization
      because of their short-lived nature. Here we present the structures of all the
      major states involved in the folding process of a PDZ domain, which include an
      off-pathway misfolded intermediate. By using a combination of kinetic, protein
      engineering, biophysical and computational techniques, we show that the misfolded
      intermediate is characterized by an alternative packing of the N-terminal beta
      hairpin onto an otherwise native-like scaffold. Our results suggest a mechanism
      of formation of incorrectly folded transient compact states by which misfolded
      structural elements are assembled together with more extended native-like
      regions.

PMID- 21076400
TI  - Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane
      proximal external region.
AB  - The monoclonal antibody 13H11 shares part of its epitope in the HIV-1 gp41
      membrane-proximal external region (MPER) with the rare, broadly neutralizing
      human antibody 2F5. Although 13H11 partially cross-blocked 2F5 binding, 13H11 is
      non-neutralizing and does not block 2F5 neutralization. We show that unlike 2F5,
      13H11 binds to a well-defined helical MPER structure that is consistent with the
      structure of gp41 in a post-fusion six-helix bundle conformation.

PMID- 21076401
TI  - BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping.
AB  - The tumor suppressor protein BRCA2 is a key component of the homologous
      recombination pathway of DNA repair, acting as the loader of RAD51 recombinase at
      sites of double-strand breaks. Here we show that BRCA2 associates with telomeres
      during the S and G2 phases of the cell cycle and facilitates the loading of RAD51
      onto telomeres. Conditional deletion of Brca2 and inhibition of Rad51 in mouse
      embryonic fibroblasts (MEFs), but not inactivation of Brca1, led to shortening of
      telomeres and accumulation of fragmented telomeric signals--a hallmark of
      telomere fragility that is associated with replication defects. These findings
      suggest that BRCA2-mediated homologous recombination reactions contribute to the
      maintenance of telomere length by facilitating telomere replication and imply
      that BRCA2 has an essential role in maintaining telomere integrity during
      unchallenged cell proliferation. Mouse mammary tumors that lacked Brca2
      accumulated telomere dysfunction-induced foci. Human breast tumors in which BRCA2
      was mutated had shorter telomeres than those in which BRCA1 was mutated,
      suggesting that the genomic instability in BRCA2-deficient tumors was due in part
      to telomere dysfunction.

PMID- 21076402
TI  - Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and
      non-neutralizing antibodies.
AB  - HIV-1 envelope glycoprotein gp41 undergoes large conformational changes to drive
      fusion of viral and target cell membranes, adopting at least three distinct
      conformations during the viral entry process. Neutralizing antibodies against
      gp41 block HIV-1 infection by targeting gp41's membrane-proximal external region
      in a fusion-intermediate state. Here we report biochemical and structural
      evidence that non-neutralizing antibodies, capable of binding with high affinity
      to an immunodominant segment adjacent to the neutralizing epitopes in the
      membrane-proximal region, recognize a gp41 conformation that exists only when
      membrane fusion is complete. We propose that these non-neutralizing antibodies
      are induced in HIV-1-infected individuals by gp41 in a triggered, postfusion form
      and contribute to production of ineffective humoral responses. These results have
      important implications for gp41-based vaccine design.

PMID- 21076403
TI  - Nanobiotechnology: sequencing at the end of the tunnel.

PMID- 21076404
TI  - Identifying single bases in a DNA oligomer with electron tunnelling.
AB  - It has been proposed that single molecules of DNA could be sequenced by measuring
      the physical properties of the bases as they pass through a nanopore. Theoretical
      calculations suggest that electron tunnelling can identify bases in single
      stranded DNA without enzymatic processing, and it was recently experimentally
      shown that tunnelling can sense individual nucleotides and nucleosides. Here, we
      report that tunnelling electrodes functionalized with recognition reagents can
      identify a single base flanked by other bases in short DNA oligomers. The
      residence time of a single base in a recognition junction is on the order of a
      second, but pulling the DNA through the junction with a force of tens of
      piconewtons would yield reading speeds of tens of bases per second.

PMID- 21076405
TI  - Atomic-scale engineering of electrodes for single-molecule contacts.
AB  - The transport of charge through a conducting material depends on the intrinsic
      ability of the material to conduct current and on the charge injection efficiency
      at the contacts between the conductor and the electrodes carrying current to and
      from the material. According to theoretical considerations, this concept remains
      valid down to the limit of single-molecule junctions. Exploring this limit in
      experiments requires atomic-scale control of the junction geometry. Here we
      present a method for probing the current through a single C(60) molecule while
      changing, one by one, the number of atoms in the electrode that are in contact
      with the molecule. We show quantitatively that the contact geometry has a strong
      influence on the conductance. We also find a crossover from a regime in which the
      conductance is limited by charge injection at the contact to a regime in which
      the conductance is limited by scattering at the molecule. Thus, the concepts of
      'good' and 'bad' contacts, commonly used in macro- and mesoscopic physics, can
      also be applied at the molecular scale.

PMID- 21076406
TI  - Resequencing of 31 wild and cultivated soybean genomes identifies patterns of
      genetic diversity and selection.
AB  - We report a large-scale analysis of the patterns of genome-wide genetic variation
      in soybeans. We re-sequenced a total of 17 wild and 14 cultivated soybean genomes
      to an average of approximately *5 depth and >90% coverage using the Illumina
      Genome Analyzer II platform. We compared the patterns of genetic variation
      between wild and cultivated soybeans and identified higher allelic diversity in
      wild soybeans. We identified a high level of linkage disequilibrium in the
      soybean genome, suggesting that marker-assisted breeding of soybean will be less
      challenging than map-based cloning. We report linkage disequilibrium block
      location and distribution, and we identified a set of 205,614 tag SNPs that may
      be useful for QTL mapping and association studies. The data here provide a
      valuable resource for the analysis of wild soybeans and to facilitate future
      breeding and quantitative trait analysis.

PMID- 21076407
TI  - A de novo paradigm for mental retardation.
AB  - The per-generation mutation rate in humans is high. De novo mutations may
      compensate for allele loss due to severely reduced fecundity in common
      neurodevelopmental and psychiatric diseases, explaining a major paradox in
      evolutionary genetic theory. Here we used a family based exome sequencing
      approach to test this de novo mutation hypothesis in ten individuals with
      unexplained mental retardation. We identified and validated unique non-synonymous
      de novo mutations in nine genes. Six of these, identified in six different
      individuals, are likely to be pathogenic based on gene function, evolutionary
      conservation and mutation impact. Our findings provide strong experimental
      support for a de novo paradigm for mental retardation. Together with de novo copy
      number variation, de novo point mutations of large effect could explain the
      majority of all mental retardation cases in the population.

PMID- 21076408
TI  - Overexpression of Fto leads to increased food intake and results in obesity.
AB  - Genome-wide association studies have identified SNPs within FTO, the human fat
      mass and obesity-associated gene, that are strongly associated with obesity.
      Individuals homozygous for the at-risk rs9939609 A allele weigh, on average, ~3
      kg more than individuals with the low-risk T allele. Mice that lack FTO function
      and/or Fto expression display increased energy expenditure and a lean phenotype.
      We show here that ubiquitous overexpression of Fto leads to a dose-dependent
      increase in body and fat mass, irrespective of whether mice are fed a standard or
      a high-fat diet. Our results suggest that increased body mass results primarily
      from increased food intake. Mice with increased Fto expression on a high-fat diet
      develop glucose intolerance. This study provides the first direct evidence that
      increased Fto expression causes obesity in mice.

PMID- 21076410
TI  - Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome
      disjunction.
AB  - During interphase, centrosomes are held together by a proteinaceous linker that
      connects the proximal ends of the mother and daughter centriole. This linker is
      disassembled at the onset of mitosis in a process known as centrosome
      disjunction, thereby facilitating centrosome separation and bipolar spindle
      formation. The NIMA (never in mitosis A)-related kinase Nek2A is implicated in
      disconnecting the centrosomes through disjoining the linker proteins C-Nap1 and
      rootletin. However, the mechanisms controlling centrosome disjunction remain
      poorly understood. Here, we report that two Hippo pathway components, the
      mammalian sterile 20-like kinase 2 (Mst2) and the scaffold protein Salvador
      (hSav1), directly interact with Nek2A and regulate its ability to localize to
      centrosomes, and phosphorylate C-Nap1 and rootletin. Furthermore, we demonstrate
      that the hSav1-Mst2-Nek2A centrosome disjunction pathway becomes essential for
      bipolar spindle formation on partial inhibition of the kinesin-5 Eg5. We propose
      that hSav1-Mst2-Nek2A and Eg5 have distinct, but complementary functions, in
      centrosome disjunction.

PMID- 21076409
TI  - Common variants in 22 loci are associated with QRS duration and cardiac
      ventricular conduction.
AB  - The QRS interval, from the beginning of the Q wave to the end of the S wave on an
      electrocardiogram, reflects ventricular depolarization and conduction time and is
      a risk factor for mortality, sudden death and heart failure. We performed a
      genome-wide association meta-analysis in 40,407 individuals of European descent
      from 14 studies, with further genotyping in 7,170 additional Europeans, and we
      identified 22 loci associated with QRS duration (P < 5 * 10(-8)). These loci map
      in or near genes in pathways with established roles in ventricular conduction
      such as sodium channels, transcription factors and calcium-handling proteins, but
      also point to previously unidentified biologic processes, such as kinase
      inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a
      candidate gene at the most significantly associated locus in this study, is
      expressed in the mouse ventricular conduction system, and treatment with a
      selective SCN10A blocker prolongs QRS duration. These findings extend our current
      knowledge of ventricular depolarization and conduction.

PMID- 21076411
TI  - The N-end rule pathway is mediated by a complex of the RING-type Ubr1 and HECT
      type Ufd4 ubiquitin ligases.
AB  - Substrates of the N-end rule pathway are recognized by the Ubr1 E3 ubiquitin
      ligase through their destabilizing amino-terminal residues. Our previous work
      showed that the Ubr1 E3 and the Ufd4 E3 together target an internal degradation
      signal (degron) of the Mgt1 DNA repair protein. Ufd4 is an E3 enzyme of the
      ubiquitin-fusion degradation (UFD) pathway that recognizes an N-terminal
      ubiquitin moiety. Here we show that the RING-type Ubr1 E3 and the HECT-type Ufd4
      E3 interact, both physically and functionally. Although Ubr1 can recognize and
      polyubiquitylate an N-end rule substrate in the absence of Ufd4, the Ubr1-Ufd4
      complex is more processive in that it produces a longer substrate-linked
      polyubiquitin chain. Conversely, Ubr1 can function as a polyubiquitylation
      enhancing component of the Ubr1-Ufd4 complex in its targeting of UFD substrates.
      We also found that Ubr1 can recognize the N-terminal ubiquitin moiety. These and
      related advances unify two proteolytic systems that have been studied separately
      for two decades.

PMID- 21076412
TI  - The orphan nuclear receptor Nurr1 restricts the proliferation of haematopoietic
      stem cells.
AB  - Successful haematopoiesis requires long-term retention of haematopoietic stem
      cells (HSCs) in a quiescent state. The transcriptional regulation of stem cell
      quiescence, especially by factors with specific functions in HSCs, is only
      beginning to be understood. Here, we demonstrate that Nurr1, a nuclear receptor
      transcription factor, has such a regulatory role. Overexpression of Nurr1 drives
      early haematopoietic progenitors into quiescence. When stem cells overexpressing
      Nurr1 are transplanted into lethally irradiated mice, they localize to the bone
      marrow, but do not contribute to regeneration of the blood system. Furthermore,
      the loss of only one allele of Nurr1 is sufficient to induce HSCs to enter the
      cell cycle and proliferate. Molecular analysis revealed an association between
      Nurr1 overexpression and upregulation of the cell-cycle inhibitor p18 (also known
      as INK4C), suggesting a mechanism by which Nurr1 could regulate HSC quiescence.
      Our findings provide critical insight into the transcriptional control mechanisms
      that determine whether HSCs remain dormant or enter the cell cycle and begin to
      proliferate.

PMID- 21076413
TI  - Caenorhabditis elegans EFA-6 limits microtubule growth at the cell cortex.
AB  - Microtubules are polymers of tubulin heterodimers that exhibit dynamic
      instability: periods of growth followed by periods of shrinkage. However, the
      molecular regulation of dynamic instability remains elusive. Here, we show that
      EFA-6, a cortically-localized protein, limits the growth of microtubules near the
      cell cortex of early embryonic cells from Caenorhabditis elegans, possibly by
      inducing microtubule catastrophes. Compared with wild type, embryos lacking EFA-6
      had abnormally long and dense microtubules at the cell cortex, and growing
      microtubule plus ends resided at the cortex for up to five-fold longer. Loss of
      EFA-6 also caused excess centrosome separation and displacement towards the cell
      cortex early in mitosis, and subsequently a loss of anaphase spindle-pole
      oscillations and increased rates of spindle elongation. The centrosome separation
      phenotype was dependent on the motor protein dynein, suggesting a possible link
      between the modulation of microtubule dynamics at the cortex and dynein-dependent
      force production. EFA-6 orthologues activate ARF6-type GTPases to regulate
      vesicle trafficking. However, we show that only the C. elegans EFA-6 amino
      terminus is both necessary and sufficient to limit microtubule growth along the
      cortex, and that this function is independent of ARF-6.

PMID- 21076414
TI  - Competition amongst Eph receptors regulates contact inhibition of locomotion and
      invasiveness in prostate cancer cells.
AB  - Metastatic cancer cells typically fail to halt migration on contact with non
      cancer cells. This invasiveness is in contrast to normal mesenchymal cells that
      retract on contact with another cell. Why cancer cells are defective in contact
      inhibition of locomotion is not understood. Here, we analyse the dynamics of
      prostate cancer cell lines co-cultured with fibroblasts, and demonstrate that a
      combinatorial code of Eph receptor activation dictates whether cell migration
      will be contact inhibited. The unimpeded migration of metastatic PC-3 cells
      towards fibroblasts is dependent on activation of EphB3 and EphB4 by ephrin-B2,
      which we show activates Cdc42 and cell migration. Knockdown of EphB3 and EphB4
      restores contact inhibition of locomotion to PC-3 cells. Conversely, homotypic
      collisions between two cancer cells results in contact inhibition of locomotion,
      mediated by EphA-Rho-Rho kinase (ROCK) signalling. Thus, the migration of cancer
      cells can switch from restrained to invasive, depending on the Eph-receptor
      profile of the cancer cell and the reciprocal ephrin ligands expressed by
      neighbouring cells.

PMID- 21076415
TI  - The role of prenucleation clusters in surface-induced calcium phosphate
      crystallization.
AB  - Unravelling the processes of calcium phosphate formation is important in our
      understanding of both bone and tooth formation, and also of pathological
      mineralization, for example in cardiovascular disease. Serum is a metastable
      solution from which calcium phosphate precipitates in the presence of calcifiable
      templates such as collagen, elastin and cell debris. A pathological deficiency of
      inhibitors leads to the uncontrolled deposition of calcium phosphate. In bone and
      teeth the formation of apatite crystals is preceded by an amorphous calcium
      phosphate (ACP) precursor phase. ACP formation is thought to proceed through
      prenucleation clusters--stable clusters that are present in solution already
      before nucleation--as was recently demonstrated for CaCO(3) (refs 15,16).
      However, the role of such nanometre-sized clusters as building blocks for ACP has
      been debated for many years. Here we demonstrate that the surface-induced
      formation of apatite from simulated body fluid starts with the aggregation of
      prenucleation clusters leading to the nucleation of ACP before the development of
      oriented apatite crystals.

PMID- 21076416
TI  - Electric-field control of spin waves at room temperature in multiferroic BiFeO3.
AB  - To face the challenges lying beyond present technologies based on complementary
      metal-oxide-semiconductors, new paradigms for information processing are
      required. Magnonics proposes to use spin waves to carry and process information,
      in analogy with photonics that relies on light waves, with several advantageous
      features such as potential operation in the terahertz range and excellent
      coupling to spintronics. Several magnonic analog and digital logic devices have
      been proposed, and some demonstrated. Just as for spintronics, a key issue for
      magnonics is the large power required to control/write information
      (conventionally achieved through magnetic fields applied by strip lines, or by
      spin transfer from large spin-polarized currents). Here we show that in BiFeO(3),
      a room-temperature magnetoelectric material, the spin-wave frequency (>600 GHz)
      can be tuned electrically by over 30%, in a non-volatile way and with virtually
      no power dissipation. Theoretical calculations indicate that this effect
      originates from a linear magnetoelectric effect related to spin-orbit coupling
      induced by the applied electric field. We argue that these properties make
      BiFeO(3) a promising medium for spin-wave generation, conversion and control in
      future magnonics architectures.

PMID- 21076417
TI  - Direct observation of the temporal and spatial dynamics during crumpling.
AB  - Crumpling occurs when a thin deformable sheet is crushed under an external load
      or grows within a confining geometry. Crumpled sheets have large resistance to
      compression and their elastic energy is focused into a complex network of
      localized structures. Different aspects of crumpling have been studied
      theoretically, experimentally and numerically. However, very little is known
      about the dynamic evolution of three-dimensional spatial configurations of
      crumpling sheets. Here we present direct measurements of the configurations of a
      fully elastic sheet evolving during the dynamic process of crumpling under
      isotropic confinement. We observe the formation of a network of ridges and
      vertices into which the energy is localized. The network is dynamic. Its
      evolution involves movements of ridges and vertices. Although the characteristics
      of ridges agree with theoretical predictions, the measured accumulation of
      elastic energy within the entire sheet is considerably slower than predicted.
      This could be a result of the observed network rearrangement during crumpling.

PMID- 21076418
TI  - A defined glycosaminoglycan-binding substratum for human pluripotent stem cells.
AB  - To exploit the full potential of human pluripotent stem cells for regenerative
      medicine, developmental biology and drug discovery, defined culture conditions
      are needed. Media of known composition that maintain human embryonic stem (hES)
      cells have been developed, but finding chemically defined, robust substrata has
      proven difficult. We used an array of self-assembled monolayers to identify
      peptide surfaces that sustain pluripotent stem cell self-renewal. The effective
      substrates displayed heparin-binding peptides, which can interact with cell
      surface glycosaminoglycans and could be used with a defined medium to culture hES
      cells for more than 3 months. The resulting cells maintained a normal karyotype
      and had high levels of pluripotency markers. The peptides supported growth of
      eight pluripotent cell lines on a variety of scaffolds. Our results indicate that
      synthetic substrates that recognize cell-surface glycans can facilitate the long
      term culture of pluripotent stem cells.

PMID- 21076419
TI  - Three-dimensional cellular ultrastructure resolved by X-ray microscopy.
AB  - We developed an X-ray microscope using partially coherent object illumination
      instead of previously used quasi-incoherent illumination. The design permitted
      the incorporation of a cryogenic tilt stage, enabling tomography of frozen
      hydrated, intact adherent cells. We obtained three-dimensional reconstructions of
      mouse adenocarcinoma cells at ~36-nm (Rayleigh) and ~70-nm (Fourier ring
      correlation) resolution, which allowed us to visualize the double nuclear
      membrane, nuclear pores, nuclear membrane channels, mitochondrial cristae and
      lysosomal inclusions.

PMID- 21076420
TI  - Measurement of mechanical tractions exerted by cells in three-dimensional
      matrices.
AB  - Quantitative measurements of cell-generated forces have heretofore required that
      cells be cultured on two-dimensional substrates. We describe a technique to
      quantitatively measure three-dimensional traction forces exerted by cells fully
      encapsulated in well-defined elastic hydrogel matrices. Using this approach we
      measured traction forces for several cell types in various contexts and revealed
      patterns of force generation attributable to morphologically distinct regions of
      cells as they extend into the surrounding matrix.

PMID- 21076421
TI  - Quantitative analysis of fitness and genetic interactions in yeast on a genome
      scale.
AB  - Global quantitative analysis of genetic interactions is a powerful approach for
      deciphering the roles of genes and mapping functional relationships among
      pathways. Using colony size as a proxy for fitness, we developed a method for
      measuring fitness-based genetic interactions from high-density arrays of yeast
      double mutants generated by synthetic genetic array (SGA) analysis. We identified
      several experimental sources of systematic variation and developed normalization
      strategies to obtain accurate single- and double-mutant fitness measurements,
      which rival the accuracy of other high-resolution studies. We applied the SGA
      score to examine the relationship between physical and genetic interaction
      networks, and we found that positive genetic interactions connect across
      functionally distinct protein complexes revealing a network of genetic
      suppression among loss-of-function alleles.

PMID- 21076422
TI  - Functional organization for color and orientation in macaque V4.
AB  - Visual area V4 in the macaque monkey is a cortical area that is strongly involved
      in color and shape perception. However, fundamental questions about V4 are still
      debated. V4 was initially characterized as a color-processing area, but
      subsequent studies revealed that it contains a diverse complement of cells,
      including those with preference for color, orientation, disparity and higher
      order feature preferences. This has led to disputes and uncertainty about the
      role of V4 in vision. Using intrinsic signal optical imaging methods in awake,
      behaving monkeys, we found that different feature preferences are functionally
      organized in V4. Optical images revealed that regions with preferential response
      to color were largely separate from orientation-selective regions. Our results
      help to resolve long-standing controversies regarding functional diversity and
      retinotopy in V4 and indicate the presence of spatially biased distribution of
      featural representation in V4 in the ventral visual pathway.

PMID- 21076423
TI  - TRPV1 activation by endogenous anandamide triggers postsynaptic long-term
      depression in dentate gyrus.
AB  - The transient receptor potential TRPV1 is a nonselective cation channel that
      mediates pain sensations and is commonly activated by a wide variety of exogenous
      and endogenous, physical and chemical stimuli. Although TRPV1 receptors are
      mainly found in nociceptive neurons of the peripheral nervous system, these
      receptors have also been found in the brain, where their role is far less
      understood. Activation of TRPV1 reportedly regulates neurotransmitter release at
      several central synapses. However, we found that TRPV1 suppressed excitatory
      transmission in rat and mouse dentate gyrus by regulating postsynaptic function
      in an input-specific manner. This suppression was a result of Ca(2+)-calcineurin
      and clathrin-dependent internalization of AMPA receptors. Moreover, synaptic
      activation of TRPV1 triggered a form of long-term depression (TRPV1-LTD) mediated
      by the endocannabinoid anandamide in a type 1 cannabinoid receptor-independent
      manner. Thus, our findings reveal a previously unknown form of endocannabinoid-
      and TRPV1-mediated regulation of synaptic strength at central synapses.

PMID- 21076424
TI  - Postsynaptic TRPV1 triggers cell type-specific long-term depression in the
      nucleus accumbens.
AB  - Synaptic modifications in the nucleus accumbens (NAc) are important for adaptive
      and pathological reward-dependent learning. Medium spiny neurons (MSNs), the
      major cell type in the NAc, participate in two parallel circuits that subserve
      distinct behavioral functions, yet little is known about differences in their
      electrophysiological and synaptic properties. Using bacterial artificial
      chromosome transgenic mice, we found that synaptic activation of group I
      metabotropic glutamate receptors in NAc MSNs in the indirect, but not direct,
      pathway led to the production of endocannabinoids, which activated presynaptic
      CB1 receptors to trigger endocannabinoid-mediated long-term depression (eCB-LTD)
      as well as postsynaptic transient receptor potential vanilloid 1 (TRPV1) channels
      to trigger a form of LTD resulting from endocytosis of AMPA receptors. These
      results reveal a previously unknown action of TRPV1 channels and indicate that
      the postsynaptic generation of endocannabinoids can modulate synaptic strength in
      a cell type-specific fashion by activating distinct pre- and postsynaptic
      targets.

PMID- 21076425
TI  - HCN channelopathy in external globus pallidus neurons in models of Parkinson's
      disease.
AB  - Parkinson's disease is a common neurodegenerative disorder characterized by a
      profound motor disability that is traceable to the emergence of synchronous,
      rhythmic spiking in neurons of the external segment of the globus pallidus (GPe).
      The origins of this pathophysiology are poorly defined for the generation of
      pacemaking. After the induction of a parkinsonian state in mice, there was a
      progressive decline in autonomous GPe pacemaking, which normally serves to
      desynchronize activity. The loss was attributable to the downregulation of an ion
      channel that is essential in pacemaking, the hyperpolarization and cyclic
      nucleotide-gated (HCN) channel. Viral delivery of HCN2 subunits restored
      pacemaking and reduced burst spiking in GPe neurons. However, the motor
      disability induced by dopamine (DA) depletion was not reversed, suggesting that
      the loss of pacemaking was a consequence, rather than a cause, of key network
      pathophysiology, a conclusion that is consistent with the ability of L-type
      channel antagonists to attenuate silencing after DA depletion.

PMID- 21076426
TI  - The columnar and laminar organization of inhibitory connections to neocortical
      excitatory cells.
AB  - The cytoarchitectonic similarities of different neocortical regions have given
      rise to the idea of 'canonical' connectivity between excitatory neurons of
      different layers within a column. It is unclear whether similarly general
      organizational principles also exist for inhibitory neocortical circuits. Here we
      delineate and compare local inhibitory-to-excitatory wiring patterns in all
      principal layers of primary motor (M1), somatosensory (S1) and visual (V1)
      cortex, using genetically targeted photostimulation in a mouse knock-in line that
      conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory
      inputs to excitatory neurons derived largely from the same cortical layer within
      a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B
      received extensive translaminar inhibition. These neurons were prominent in V1,
      where they might correspond to complex cells, less numerous in barrel cortex and
      absent in M1. Although inhibitory connection patterns were stereotypical, the
      abundance of individual motifs varied between regions and cells, potentially
      reflecting functional specializations.

PMID- 21076427
TI  - Extensive spontaneous plasticity of corticospinal projections after primate
      spinal cord injury.
AB  - Although axonal regeneration after CNS injury is limited, partial injury is
      frequently accompanied by extensive functional recovery. To investigate
      mechanisms underlying spontaneous recovery after incomplete spinal cord injury,
      we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed
      behavioral, electrophysiological and anatomical adaptations. We found marked
      spontaneous plasticity of corticospinal projections, with reconstitution of fully
      60% of pre-lesion axon density arising from sprouting of spinal cord midline
      crossing axons. This extensive anatomical recovery was associated with
      improvement in coordinated muscle recruitment, hand function and locomotion.
      These findings identify what may be the most extensive natural recovery of
      mammalian axonal projections after nervous system injury observed to date,
      highlighting an important role for primate models in translational disease
      research.

PMID- 21076432
TI  - What a difference a day makes! The contribution of intrinsic FGF9 signalling to
      germline masculinisation.

PMID- 21076434
TI  - Our experience in sperm morphology assessment.

PMID- 21076433
TI  - Leukocytes and oxidative stress: dilemma for sperm function and male fertility.
AB  - Spermatozoa are constantly exposed to the interphase between oxidation through
      high amounts of reactive oxygen species (ROS) and leukocytes, and reduction by
      means of scavengers and antioxidants. Considering the very special functions as
      being the only cells with such high polarization and exerting their functions
      outside the body, even in a different individual, the female genital tract, the
      membranes of these cells are chemically composed of an extraordinary high amount
      of polyunsaturated fatty acids. This in turn, renders them very susceptible to
      oxidative stress, which is defined as an imbalance between oxidation and
      reduction towards the oxidative status. As a result, ROS deriving from both
      leukocytes and the male germ cells themselves cause a process called 'lipid
      peroxidation' and other damages to the sperm cell. On the other hand, a certain
      limited amount of ROS is essential in order to trigger vital physiological
      reactions in cells, including capacitation or the acrosome reaction in sperm. The
      treatment of patients with antioxidants to compensate the oxidative status caused
      by oxidative stress is highly debated as uncontrolled antioxidative treatment
      might derail the system towards the reduced status, which is also unphysiological
      and can even induce cancer. This paradox is called the 'antioxidant paradox'.
      Therefore, a proper andrological diagnostic work-up, including the evaluation of
      ROS levels and the antioxidant capacity of the semen, has to be carried out
      beforehand, aimed at keeping the fine balance between oxidation and scavenging of
      vital amounts of ROS.

PMID- 21076435
TI  - Proteomics of spermatogenesis: from protein lists to understanding the regulation
      of male fertility and infertility.
AB  - Proteomic technologies have undergone significant development in recent years,
      which has led to extensive advances in protein research. Currently, proteomic
      approaches have been applied to many scientific areas, including basic research,
      various disease and malignant tumour diagnostics, biomarker discovery and other
      therapeutic applications. In addition, proteomics-driven research articles
      examining reproductive biology and medicine are becoming increasingly common. The
      key challenge for this field is to move from lists of identified proteins to
      obtaining biological information regarding protein function. The present article
      reviews the available scientific literature related to spermatogenesis. In
      addition, this study uses two-dimensional electrophoresis mass spectrometry (2DE
      MS) and liquid chromatography (LC)-MS to construct a series of proteome profiles
      describing spermatogenesis. This large-scale identification of proteins provides
      a rich resource for elucidating the mechanisms underlying male fertility and
      infertility.

PMID- 21076436
TI  - Copy number variation associated with Kallmann syndrome: new genetics insights
      from genome-wide studies.

PMID- 21076437
TI  - The epididymis, cytoplasmic droplets and male fertility.
AB  - The potential of spermatozoa to become motile during post-testicular maturation,
      and the relationship between the cytoplasmic droplet and fertilizing capacity are
      reviewed. Post-testicular maturation of spermatozoa involves the autonomous
      induction of motility, which can occur in vivo in testes with occluded excurrent
      ducts and in vitro in testicular explants, and artefactual changes in morphology
      that appear to occur in the testis in vitro. Both modifications may reflect time
      dependent oxidation of disulphide bonds of head and tail proteins. Regulatory
      volume decrease (RVD), which counters sperm swelling at ejaculation, is discussed
      in relation to loss of cytoplasmic droplets and consequences for fertility. It is
      postulated that: (i) fertile males possess spermatozoa with sufficient osmolytes
      to drive RVD at ejaculation, permitting the droplet to round up and pinch off
      without membrane rupture; and (ii) infertile males possess spermatozoa with
      insufficient osmolytes so that RVD is inadequate, the droplet swells and the
      resulting flagellar angulation prevents droplet loss. Droplet retention at
      ejaculation is a harbinger of infertility caused by failure of the spermatozoon
      to negotiate the uterotubal junction or mucous and reach the egg. In this
      hypothesis, the epididymis regulates fertility indirectly by the extent of
      osmolyte provision to spermatozoa, which influences RVD and therefore droplet
      loss. Man is an exception, because ejaculated human spermatozoa retain their
      droplets. This may reflect their short midpiece, approximating head length,
      permitting a swollen droplet to extend along the entire midpiece; this not only
      obviates droplet migration and flagellar angulation but also hampers droplet
      loss.

PMID- 21076438
TI  - Measurement and significance of sperm morphology.
AB  - The measurement or evaluation and clinical significance of human sperm morphology
      has always been and still is a controversial aspect of the semen analysis for the
      determination of a male's fertility potential. In this review the background of
      the development of the evaluation criteria for sperm morphology will be
      discussed. Aspects of criticism on the strict criteria definition and use of the
      criteria for sperm morphology evaluation will be discussed as well as possible
      reasons for the decline in normal sperm morphology values and how we can
      compromise for this phenomenon resulting in the very low normal reference value
      as published in the 2010 WHO manual for the Examination and Processing of Human
      Semen. One of the possible solutions may be to give more attention to a limited
      number of abnormal sperm morphology categories and the inclusion of sperm
      morphology patterns. It is concluded in this review that if done correctly and
      with care and with strict application of existing guidelines as outlined in the
      2010 WHO manual, sperm morphology measurement still has a very important role to
      play in the clinical evaluation of male fertility potential.

PMID- 21076440
TI  - Epidemiology of sexual dysfunction in Asia compared to the rest of the world.
AB  - There have been a limited number of epidemiological studies published on sexual
      disorders in persons from Asia. This paper aims to assess the reports of sexual
      dysfunction epidemiological studies published in the English language that
      involved Asian countries. Key points are summarized in this paper from nine
      epidemiological papers on sexual dysfunction from Asia that were published in the
      English language. Seven met the criteria for evidence-based studies reaching a
      Prins score of at least 10 or more. Papers included in this report came from
      national and regional representative studies in peer review journals. These
      results for sexual dysfunction in the nine papers are summarized for various
      sexual dysfunctions in men and women in Asian countries. In three of these,
      worldwide data were presented in the same paper allowing comparisons with Asian
      data on prevalence rates. Detailed descriptions from each of these studies are
      presented in paragraph form. More detailed data on erectile dysfunction (ED) is
      presented in a tabular form. Collectively, there seems to be a need for country-
      and population-specific further descriptive and analytical epidemiological
      studies in all of the sexual disorders from Asia. This critical review paper
      should help guide these studies for reaching evidence-based literature standards.

PMID- 21076439
TI  - Effects of varicocele on testosterone, apoptosis and expression of StAR mRNA in
      rat Leydig cells.
AB  - The aim of this study was to explore the effects of varicocele on the morphology
      and function of Leydig cells in the rat testis. Forty male Sprague-Dawley rats
      were divided into two groups: the experimental group underwent surgery to create
      a left varicocele (VC), and the control group underwent a sham operation. Serum
      testosterone and intratesticular testosterone levels were measured using a
      radioimmunoassay after 4 and 8 weeks of operation. Leydig cells were studied for
      apoptosis and expression of steroidogenetic acute regulatory (StAR) protein mRNA
      levels. Serum testosterone levels declined after 4 and 8 weeks of operation but
      were not significant (P>0.05). However, the intratesticular testosterone levels
      after 8 weeks were significantly decreased compared with the control group
      (P<0.01). The mean apoptosis index of Leydig cells in the experimental group was
      significantly higher than that in the control group after 4 or 8 weeks (P<0.01).
      StAR mRNA levels in the Leydig cells of the experimental group were significantly
      lower compared to those of the control group (P<0.01). Our data show that
      varicocele did impair Leydig cell function by increasing apoptosis and
      suppressing the expression of the StAR protein.

PMID- 21076441
TI  - Selective cell death mediated by small conditional RNAs: a novel therapeutic
      approach to cancer therapy.

PMID- 21076444
TI  - Klotho, FGF23, and FGF receptors in chronic kidney disease: a yin-yang situation?
AB  - Secondary hyperparathyroidism in chronic kidney disease (CKD) develops in
      response to disturbances in calcium and phosphate metabolism associated with CKD,
      including FGF23 and klotho. FGF23 activates its receptor FGFR1, splice variant
      IIIC, in the parathyroid gland via a klotho-dependent mechanism and suppresses
      parathyroid hormone (PTH) secretion. Klotho also may regulate PTH secretion in an
      FGF23-independent mode, by modulating parathyroid Na+/K+-ATPase activity. The
      persistence of hyperparathyroidism with progressing CKD despite high serum FGF23
      is indicative of FGF23 resistance.

PMID- 21076445
TI  - Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy.
AB  - Tenofovir, used in combination with other antiretroviral agents, is an effective
      therapy for HIV infection. Although large clinical studies and post-marketing
      data support a benign renal profile for tenofovir, numerous cases of kidney
      injury raise concern for nephrotoxic potential. Early human studies and
      experimental evidence suggested that tenofovir itself was not associated with
      mitochondrial toxicity within the kidney. However, recent animal data demonstrate
      that tenofovir causes mitochondrial DNA depletion and mitochondrial toxicity.
      Herlitz et al. confirm the nephrotoxicity of tenofovir in humans. They describe
      its clinical consequences, histopathologic findings, and its mitochondrial
      toxicity in HIV+ patients.

PMID- 21076446
TI  - Probiotics and dietary manipulations in calcium oxalate nephrolithiasis: two
      sides of the same coin?
AB  - Growing evidence has assigned to oxalate a pivotal role in calcium
      nephrolithiasis pathophysiology. A better understanding of the mechanisms behind
      intestinal absorption and renal excretion has led to the identification of new
      treatments. Among these, diet and probiotics appear promising in terms of safety
      and rationale. However, the discrepancy between in vitro and in vivo results
      requires further studies to identify the right patient target, the correct
      dosage, and the real modification of natural and clinical history of
      nephrolithiasis.

PMID- 21076447
TI  - Potential benefits of alkali therapy to prevent GFR loss: time for a palatable
      'solution' for the management of CKD.
AB  - There is increasing evidence that alkali therapy can retard progression of
      chronic kidney disease (CKD). We summarize recent studies and discuss a mechanism
      whereby alkali therapy may neutralize acid production associated with typical
      Western diets, which generate acid. We emphasize the rationale for using alkali
      therapy early in the course of CKD, even in the absence of overt metabolic
      acidosis, and we urge the pharmaceutical industry to develop palatable alkali
      containing solutions.

PMID- 21076448
TI  - Comments on KDIGO clinical practice guidelines for bisphosphonate treatment of
      chronic kidney disease.

PMID- 21076451
TI  - Increased fetuin-A levels following treatment with a vitamin D analog.

PMID- 21076453
TI  - The 'ball-in-cup' lesion is not specific for human immunodeficiency virus-related
      glomerulonephritis.

PMID- 21076457
TI  - Pink urine after propofol anesthesia.

PMID- 21076458
TI  - The Case ? A blistering problem in a hemodialysis patient. The Diagnosis |
      Porphyria cutanea tarda.

PMID- 21076459
TI  - Luminal cytokeratin expression profiles of breast papillomas and papillary
      carcinomas and the utility of a cytokeratin 5/p63/cytokeratin 8/18 antibody
      cocktail in their distinction.
AB  - Luminal cytokeratin (CK) expression in breast papillary lesions, and its
      potential diagnostic utility among other markers in distinguishing between
      papillomas and papillary carcinomas, has not been previously evaluated. Such
      expression was determined in 42 papillary lesions (18 papillary carcinomas and 24
      papillomas) by immunostaining with a CK5/p63/CK8/18 antibody cocktail. The mean
      CK8/18 intensity score and percentage of positive cells were significantly higher
      in papillary carcinomas (227 and 95%, respectively, vs 86 and 42% in papillomas;
      both P-values <0.0001), whereas the mean CK5 intensity score and percentage of
      positive cells were significantly lower (7 and 5%, respectively, vs 107 and 58%
      in papillomas; both P-values <0.0001). Half (9/18) of the papillary carcinomas
      expressed p63 vs all (24/24) of the papillomas (P = 0.0001). P63 expression in
      papillary carcinoma was always (9/9; 100%) focal/limited in nature (expression in
      <10% of cells), whereas focal expression was seen in only four (17%) papillomas
      (P<0.0001). Both differential CK (CK8/18 and CK5) expression and p63 were equally
      sensitive (100%) for the diagnosis of papillary carcinoma, but differential CK
      expression was more specific (96 vs 83%), resulting in a greater accuracy.
      However, the best discriminatory power in the distinction from papilloma was
      achieved when all three markers were used in combination, resulting in 100%
      sensitivity and specificity values. It is concluded that breast papillary lesions
      have differential CK expression profiles that, especially in combination with
      p63, can be useful for their stratification, potentially also in needle biopsy
      material, in which more accurate and reproducible characterization is needed.

PMID- 21076460
TI  - Minichromosome maintenance protein 7 as a potential prognostic factor for
      progression-free survival in high-grade serous carcinomas of the ovary.
AB  - Minichromosome maintenance protein 7 (MCM7) is involved in replicative licensing
      and synthesis of DNA. It was previously identified as an overexpressed gene in
      high-grade serous carcinomas compared with serous borderline tumors of the ovary
      in cDNA microarray studies. In this study, we sought to validate MCM7 expression
      in 342 ovarian tumors on tissue microarrays. MCM7 expression was quantified as
      the MCM7 labeling index, and it was independently generated by two methods: a
      score provided by manual review of each sample by a pathologist observer and by
      an automated cellular imaging system. Analyses of MCM7 scores indicated a high
      degree of concordance and distribution between the observer- and machine
      generated MCM7 labeling indexes. MCM7 expression was significantly higher in high
      grade serous carcinomas than in serous borderline tumors or other histological
      subtypes of ovarian cancer. For both observer- and machine-derived scores,
      univariate analyses indicated the significant association of a high MCM7 labeling
      index with better progression-free survival in high-grade serous carcinomas.
      These results suggest the clinical importance of MCM7 expression in high-grade
      serous carcinomas of the ovary and the need for further evaluation of MCM7 as a
      potential prognostic factor in ovarian cancer.

PMID- 21076461
TI  - beta-Catenin pathway activation in breast cancer is associated with triple
      negative phenotype but not with CTNNB1 mutation.
AB  - Aberrant beta-catenin expression as determined by assessment of its subcellular
      localization constitutes a surrogate marker of Wnt signalling pathway activation
      and has been reported in a subset of breast cancers. The association of beta
      catenin/Wnt pathway activation with clinical outcome and the mechanisms leading
      to its activation in breast cancers still remain a matter of controversy. The
      aims of this study were to address the distribution of beta-catenin expression in
      invasive breast cancers, the correlations between beta-catenin expression and
      clinicopathological features and survival of breast cancer patients, and to
      determine whether aberrant beta-catenin expression is driven by CTNNB1 (beta
      catenin encoding gene) activating mutations. Immunohistochemistry was performed
      on a tissue microarray containing 245 invasive breast carcinomas from uniformly
      treated patients, using two anti-beta-catenin monoclonal antibodies. Selected
      samples were subjected to CTNNB1 exon 3 mutation analysis by direct gene
      sequencing. A good correlation between the two beta-catenin antibodies was
      observed (Spearman's r >0.62, P<0.001). Respectively, 31 and 11% of the cases
      displayed lack/reduction of beta-catenin membranous expression and nuclear
      accumulation. Complete lack of beta-catenin expression was significantly
      associated with invasive lobular carcinoma histological type. Subgroup analysis
      of non-lobular cancers or non-lobular grade 3 carcinomas revealed that
      lack/reduction of beta-catenin membranous expression and/or nuclear accumulation
      were significantly associated with oestrogen receptor negativity, absence of HER2
      gene amplification and overexpression, lack/reduction of E-cadherin expression
      and tumours of triple-negative and basal-like phenotype. Univariate survival
      analysis revealed a significant association between beta-catenin nuclear
      expression and shorter metastasis-free and overall survival in the whole cohort;
      however, beta-catenin nuclear expression was not an independent predictor of
      outcome in multivariate analysis. No CTNNB1 mutations were identified in the 28
      selected breast carcinomas analysed. In conclusion, beta-catenin/Wnt pathway
      activation is preferentially found in triple-negative/basal-like breast
      carcinomas, is associated with poor clinical outcome and is unlikely to be driven
      by CTNNB1 mutations in breast cancer.

PMID- 21076462
TI  - Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK
      associated tumor spectrum.
AB  - Renal cell carcinoma represents a model for contemporary classification of solid
      tumors; however, unusual and unclassifiable cases exist and are not rare in
      children and young adults. The anaplastic lymphoma kinase (ALK) gene has recently
      been implicated in subsets of pulmonary, esophageal, breast, and colon cancers.
      These findings strengthen the importance of molecular classification of
      carcinomas across different organ sites, especially considering the evolving
      targeted anticancer therapies with ALK inhibitors. In the current study of six
      pediatric renal cell carcinomas, two cases exhibited structural karyotypic
      abnormalities involving the ALK locus on chromosomal band 2p23. Fluorescence in
      situ hybridization (FISH) studies were positive for an ALK rearrangement in one
      case, and subsequent 5' rapid amplification of cDNA ends analysis of this tumor
      revealed that the 3' portion of the ALK transcript encoding for the kinase domain
      was fused in frame to the 5' portion of vinculin (VCL, NM_003373). The new fusion
      gene is predicted to have an open reading frame of 4122 bp encoding for a 1374-aa
      oncoprotein; its expression was shown by immunoblotting with anti-VCL and anti
      ALK antibodies in tumor tissue lysates. Immunohistochemistry with the same
      antibodies demonstrated cytoplasmic and subplasmalemmal localization of the
      oncoprotein determined by its N-terminal VCL portion. FISH with a custom-designed
      VCL-ALK dual-fusion probe set confirmed the presence of the fusion in neoplastic
      cells and demonstrated the potential clinical utility of this approach for
      detecting VCL-ALK in routinely processed tissue. The five remaining pediatric
      renal cell carcinomas did not show ALK rearrangement by FISH or ALK expression by
      immunohistochemistry. The data identify the kidney as a new organ site for ALK
      associated carcinomas and VCL as a novel ALK fusion partner. The results should
      prompt further studies to advance the molecular classification of renal cell
      carcinoma and help to select patients who would benefit from appropriate targeted
      therapies.

PMID- 21076463
TI  - Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using
      the novel marker DPEP1.
AB  - Distinguishing primary mucinous ovarian cancers from ovarian metastases of
      digestive organ cancers is often challenging. Dipeptidase 1 was selected as the
      candidate novel marker of colorectal cancer based on an analysis of a gene
      expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian
      metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers,
      were dipeptidase 1-positive (threshold; ?25% expression, P<0.0001). Next, five
      immunohistochemical markers (dipeptidase 1, estrogen receptor-alpha, cytokeratin
      7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a
      hierarchical clustering analysis, the mutually exclusive expression of
      cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of
      colorectal cancers (P<0.0001). In a decision tree analysis, cytokeratin 7, caudal
      type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers
      and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the
      five immunohistochemical markers were combined with six preoperative factors
      (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and
      combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7,
      caudal type homeobox 2, and tumor size) were used to generate a decision tree to
      classify primary mucinous ovarian cancers and metastases of digestive organ
      cancers with 93% accuracy. In conclusion, we identified a novel
      immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous
      ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm
      using immunohistochemical and clinical factors to distinguish metastases of
      digestive organ cancers from primary mucinous ovarian cancers will be useful to
      establish a protocol for the diagnosis of ovarian metastasis.

PMID- 21076465
TI  - Adenine nucleotide translocase family: four isoforms for apoptosis modulation in
      cancer.
AB  - Mitochondria have important functions in mammalian cells as the energy powerhouse
      and integrators of the mitochondrial pathway of apoptosis. The adenine nucleotide
      translocase (ANT) is a family of proteins involved in cell death pathways that
      perform distinctly opposite functions to regulate cell fate decisions. On the one
      hand, ANT catalyzes the adenosine triphosphate export from the mitochondrial
      matrix to the intermembrane space with the concomitant import of ADP from the
      intermembrane space to the matrix. On the other hand, during periods of stress,
      ANT could function as a lethal pore and trigger the process of mitochondrial
      membrane permeabilization, which leads irreversibly to cell death. In human, ANT
      is encoded by four homologous genes, whose expression is not only tissue
      specific, but also varies according to the pathophysiological state of the cell.
      Recent evidence revealed a differential role of the ANT isoforms in apoptosis and
      a deregulation of their expression in cancer. In this review, we introduce the
      current knowledge of ANT in apoptosis and cancer cells and propose a novel
      classification of ANT isoforms.

PMID- 21076464
TI  - Basal-like and triple-negative breast cancers: a critical review with an emphasis
      on the implications for pathologists and oncologists.
AB  - Breast cancer is a heterogeneous disease encompassing a variety of entities with
      distinct morphological features and clinical behaviors. Although morphology is
      often associated with the pattern of molecular aberrations in breast cancers, it
      is also clear that tumors of the same histological type show remarkably different
      clinical behavior. This is particularly true for 'basal-like cancer', which is an
      entity defined using gene expression analysis. The purpose of this article was to
      review the current state of knowledge of basal-like breast cancers, to discuss
      the relationship between basal-like and triple-negative breast cancers, and to
      clarify practical implications of these diagnoses for pathologists and
      oncologists.

PMID- 21076467
TI  - Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS
      induced DNA damage and premature senescence.
AB  - Approximately 20% of tumors contain activating mutations in the RAS family of
      oncogenes. As tumors progress to higher grades of malignancy, the expression of
      oncogenic RAS has been reported to increase, leading to an oncogene-induced
      senescence (OIS) response. Evasion of this senescence barrier is a hallmark of
      advanced tumors indicating that OIS serves a critical tumor-suppressive function.
      Induction of OIS has been attributed to either RAS-mediated production of
      reactive oxygen species (ROS) or to induction of a DNA damage response (DDR).
      However, functional links between these two processes in triggering the senescent
      phenotype have not been explicitly described. Our previous work has shown that,
      in cultured untransformed cells, preventing elimination of oxidized guanine
      deoxyribonucleotides, which was achieved by suppressing expression of the
      cellular 8-oxo-dGTPase, human MutT homolog 1 (MTH1), sufficed to induce a DDR as
      well as premature senescence. Here, we demonstrate that overexpression of MTH1
      can prevent the oncogenic H-RAS-induced DDR and attendant premature senescence,
      although it does not affect the observed elevation in ROS levels produced by RAS
      oncoprotein expression. Conversely, we find that loss of MTH1 preferentially
      induces an in vitro proliferation defect in tumorigenic cells overexpressing
      oncogenic RAS. These results indicate that the guanine nucleotide pool is a
      critical target for intracellular ROS produced by oncogenic RAS and that RAS
      transformed cells require robust MTH1 expression to proliferate.

PMID- 21076466
TI  - Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency
      and decreases tumor burden.
AB  - The transcription factor nuclear factor kappa B (NF-kappaB) is activated in human
      breast cancer tissues and cell lines. However, it is unclear whether NF-kappaB
      activation is a consequence of tumor formation or a contributor to tumor
      development. We developed a doxycycline (dox)-inducible mouse model, termed DNMP,
      to inhibit NF-kappaB activity specifically within the mammary epithelium during
      tumor development in the polyoma middle T oncogene (PyVT) mouse mammary tumor
      model. DNMP females and PyVT littermate controls were treated with dox from 4 to
      12 weeks of age. We observed an increase in tumor latency and a decrease in final
      tumor burden in DNMP mice compared with PyVT controls. A similar effect with
      treatment from 8 to 12 weeks indicates that outcome is independent of effects on
      postnatal virgin ductal development. In both cases, DNMP mice were less likely to
      develop lung metastases than controls. Treatment from 8 to 9 weeks was sufficient
      to impact primary tumor formation. Inhibition of NF-kappaB increases apoptosis in
      hyperplastic stages of tumor development and decreases proliferation at least in
      part by reducing Cyclin D1 expression. To test the therapeutic potential of NF
      kappaB inhibition, we generated palpable tumors by orthotopic injection of PyVT
      cells and then treated systemically with the NF-kappaB inhibitor thymoquinone
      (TQ). TQ treatment resulted in a reduction in tumor volume and weight as compared
      with vehicle-treated control. These data indicate that epithelial NF-kappaB is an
      active contributor to tumor progression and demonstrate that inhibition of NF
      kappaB could have a significant therapeutic impact even at later stages of
      mammary tumor progression.

PMID- 21076468
TI  - The ecology of brain tumors: lessons learned from neurofibromatosis-1.
AB  - Traditionally, cancer studies have primarily focused on mutations that activate
      growth or survival pathways in susceptible pre-neoplastic/neoplastic cells.
      However, recent research has revealed a critical role for non-neoplastic cells
      within the tumor microenvironment in the process of cancer formation and
      progression. In addition, the existence of regional and developmental variations
      in susceptible cell types and supportive microenvironments support a model of
      tumorigenesis in which the dynamic symbiotic relationship between neoplastic and
      non-neoplastic cell types dictate where and when cancers form and grow. In this
      review, we highlight advances in neurofibromatosis type 1 (NF1) genetically
      engineered mouse brain tumor (glioma) modeling to reveal how cellular and
      molecular heterogeneity in both the pre-neoplastic/neoplastic and non-neoplastic
      cellular compartments contribute to gliomagenesis and glioma growth.

PMID- 21076469
TI  - ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by
      regulating cell adhesion and invasion.
AB  - During the analysis of phosphotyrosine-containing proteins in scirrhous gastric
      carcinoma cell lines, we observed an unusual expression of Arf-GAP with Rho-GAP
      domain, ankyrin repeat and PH domain 3 (ARAP3), a multimodular signaling protein
      that is a substrate of Src family kinases. Unlike other phosphotyrosine proteins,
      such as CUB domain-containing protein 1 (CDCP1) and Homo sapiens chromosome 9
      open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa),
      which are overexpressed and hyperphosphorylated in scirrhous gastric carcinoma
      cell lines, ARAP3 was underexpressed in cancerous human gastric tissues. In this
      study, we found that overexpression of ARAP3 in the scirrhous gastric carcinoma
      cell lines significantly reduced peritoneal dissemination. In vitro studies also
      showed that ARAP3 regulated cell attachment to the extracellular matrix, as well
      as invasive activities. These effects were suppressed by mutations in the Rho
      GTPase-activating protein (GAP) domain or in the C-terminal two tyrosine residues
      that are phosphorylated by Src. Thus, the expression and phosphorylation state of
      ARAP3 may affect the invasiveness of cancer by modulating cell adhesion and
      motility. Our results suggest that ARAP3 is a unique Src substrate that
      suppresses peritoneal dissemination of scirrhous gastric carcinoma cells.

PMID- 21076470
TI  - The actin-associating protein Tm5NM1 blocks mesenchymal motility without
      transition to amoeboid motility.
AB  - Cell migration is an integral component of metastatic disease. The ability of
      cells to transit between mesenchymal and amoeboid modes of migration has
      complicated the development of successful therapies designed to target cell
      migration as a means of inhibiting metastasis. Therefore, investigations of the
      mechanisms that regulate cell migration and render cells stationary are
      necessary. Tropomyosins are actin-associating proteins that regulate the activity
      of several effectors of actin filament dynamics. Previously, we have shown that
      the tropomyosin isoform Tm5NM1 stabilizes actin filaments and inhibits cell
      migration in a two-dimensional culture system. Here, we show that Tm5NM1 inhibits
      the mesenchymal migration of multiple cell lines in an isoform-specific manner.
      Tm5NM1 stimulates the downregulation of Src kinase activity and a rounded or
      elliptical morphology in three-dimensional collagen gels, and cells have
      dramatically reduced capacity to form pseudopodia. Importantly, we find that
      Tm5NM1 inhibits both the mesenchymal to amoeboid and amoeboid to mesenchymal
      transitions. Collectively, our data suggest that mimicking the action of Tm5NM1
      overexpression represents an approach for effectively inhibiting the mesenchymal
      mode of migration.

PMID- 21076471
TI  - Monoclonal antibody therapy directed against human acute myeloid leukemia stem
      cells.
AB  - Accumulating evidence indicates that many human cancers are organized as a
      cellular hierarchy initiated and maintained by self-renewing cancer stem cells.
      This cancer stem cell model has been most conclusively established for human
      acute myeloid leukemia (AML), although controversies still exist regarding the
      identity of human AML stem cells (leukemia stem cell (LSC)). A major implication
      of this model is that, in order to eradicate the cancer and cure the patient, the
      cancer stem cells must be eliminated. Monoclonal antibodies have emerged as
      effective targeted therapies for the treatment of a number of human malignancies
      and, given their target antigen specificity and generally minimal toxicity, are
      well positioned as cancer stem cell-targeting therapies. One strategy for the
      development of monoclonal antibodies targeting human AML stem cells involves
      first identifying cell surface antigens preferentially expressed on AML LSC
      compared with normal hematopoietic stem cells. In recent years, a number of such
      antigens have been identified, including CD123, CD44, CLL-1, CD96, CD47, CD32,
      and CD25. Moreover, monoclonal antibodies targeting CD44, CD123, and CD47 have
      demonstrated efficacy against AML LSC in xenotransplantation models. Hopefully,
      these antibodies will ultimately prove to be effective in the treatment of human
      AML.

PMID- 21076474
TI  - Regulation of donor participation in research studies: is there another way?

PMID- 21076472
TI  - AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in
      hepatocellular carcinoma.
AB  - Yes-associated protein (YAP) is a downstream effector of the Hippo signaling
      pathway, which controls organ expansion and tissue development. We have recently
      defined the tumorigenic potential and clinical significance of the YAP1 oncogene
      in human hepatocellular carcinoma (HCC). The present study aims to define the
      tumorigenic properties of YAP in HCC and elucidate the related downstream
      signaling mechanism. In a gain-of-function study, we demonstrated that ectopic
      increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell
      line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1)
      enhanced aptitudes in cell viability, anchorage-independent growth, migration and
      invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of
      HCC biomarker alpha-fetoprotein and activation of mitogen-activated protein
      kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key
      downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated
      knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells
      and of the primary HCC cell line to proliferate and invade. These results
      indicate that AXL is a mediator of YAP-dependent oncogenic activities and
      implicates it as a potential therapeutic target for HCC.

PMID- 21076473
TI  - Claudin-2 is selectively enriched in and promotes the formation of breast cancer
      liver metastases through engagement of integrin complexes.
AB  - The liver represents the third most frequent site of metastasis in patients with
      breast cancer. We performed in vivo selection using 4T1 breast cancer cells to
      identify genes associated with the liver metastatic phenotype. Coincident with
      the loss of numerous tight-junctional proteins, we observe claudin-2
      overexpression, specifically in liver-aggressive breast cancer cells. We further
      demonstrate that claudin-2 is both necessary and sufficient for the ability of
      4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive
      breast cancer cells display a claudin-2-mediated increase in their ability to
      adhere to extracellular matrix (ECM) components, such as fibronectin and type IV
      collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the
      cell surface expression of alpha(2)beta(1)- and alpha(5)beta(1)-integrin
      complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to
      fibronectin and type IV collagen can be blocked with neutralizing antibodies that
      target alpha(5)beta(1) and alpha(2)beta(1) complexes, respectively.
      Immunohistochemical analyses reveal that claudin-2, although weakly expressed in
      primary human breast cancers, is readily detected in all liver metastasis samples
      examined to date. Together, these results uncover novel roles for claudin-2 in
      promoting breast cancer adhesion to the ECM and define its importance during
      breast cancer metastasis to the liver.

PMID- 21076475
TI  - Pooled MSCs for treatment of severe hemorrhage.

PMID- 21076476
TI  - Policy and procedures on scientific misconduct.

PMID- 21076478
TI  - The effects of palm oil breakdown products on lipid turnover and morphology of
      fungi.
AB  - The oleaginous fungi Cryptococcus curvatus and Mucor circinelloides were used to
      determine the effect of palm oil breakdown products, measured as polymerized
      triglycerides (PTGs), on lipid turnover and on fungal growth and morphology. In
      M. circinelloides, we found after 7 days of growth, a decrease in biomass and in
      lipid utilization and accumulation at increased PTG levels, both at low and
      neutral pH. In C. curvatus, there was also a decrease in lipid utilization and
      biomass production at increased PTG levels, at both low and neutral pH. However,
      an increase in oil accumulation was observed at low pH while it remained similar
      at neutral pH for all PTG levels tested. Hairy and warty protuberances on the
      cell surface were observed when C. curvatus was grown on oils with 15% and 45%
      PTGs, respectively. Using nano scanning Auger microscopy, we found no evidence to
      suggest a difference in elemental composition of the surfaces of the warty
      protuberances compared with the rest of the cell wall surface. We conclude that
      the warty protuberances are outgrowths of cell walls and that the changes
      observed in lipid turnover in both fungi are due to the presence of palm oil
      breakdown products.

PMID- 21076477
TI  - p73 is an essential regulator of neural stem cell maintenance in embryonal and
      adult CNS neurogenesis.
AB  - The p53 family member p73 is essential for brain development, but its precise
      role and scope remain unclear. Global p73 deficiency determines an overt and
      highly penetrant brain phenotype marked by cortical hypoplasia with ensuing
      hydrocephalus and hippocampal dysgenesis. The DeltaNp73 isoform is known to
      function as a prosurvival factor of mature postmitotic neurons. In this study, we
      define a novel essential role of p73 in the regulation of the neural stem cell
      compartment. In both embryonic and adult neurogenesis, p73 has a critical role in
      maintaining an adequate neurogenic pool by promoting self-renewal and
      proliferation and inhibiting premature senescence of neural stem and early
      progenitor cells. Thus, products of the p73 gene locus are essential maintenance
      factors in the central nervous system, whose broad action stretches across the
      entire differentiation arch from stem cells to mature postmitotic neurons.

PMID- 21076479
TI  - Survival of Escherichia coli O157:H7 in ruminal or fecal contents incubated with
      corn or wheat dried distillers' grains with solubles.
AB  - Dried distillers' grain with solubles (DDGS) is a by-product of ethanol
      production, and its use as cattle feed has increased as a result of the expansion
      of the fuel ethanol industry. However, the inclusion of corn DDGS into feedlot
      diets may increase the shedding of Escherichia coli O157:H7. This study
      investigated whether corn or wheat DDGS at 2 concentrations (20% or 40% vs. 100%
      barley grain) affected the survival of E. coli O157:H7 in incubations of ruminal
      digesta and feces. Neither the type nor the level of DDGS had any effect on
      fermentation or the survival of E. coli O157:H7 in ruminal digesta. However,
      there was a time by DDGS interaction (p < 0.05), where the numbers of E. coli
      O157:H7 in feces did not differ after 4 or 12 h of incubation but were greater
      after 24 h in both 40% wheat and 40% corn DDGS as compared with other treatments.
      Additionally, after 24 h, the numbers of E. coli O157:H7 were greater in fecal
      incubations with corn DDGS than with wheat DDGS (p < 0.05). The differences in
      the numbers of E. coli O157:H7 were not attributable to changes in pH or in
      concentrations of volatile fatty acids in the media. These results suggest that
      the inclusion of high levels of corn or wheat DDGS in feedlot diets of cattle may
      encourage the survival of E. coli O157:H7 in feces.

PMID- 21076480
TI  - Composts containing fluorescent pseudomonads suppress fusarium root and stem rot
      development on greenhouse cucumber.
AB  - Three composts (Ball, dairy, and greenhouse) were tested for the ability to
      suppress the development of Fusarium root and stem rot (caused by Fusarium
      oxysporum f. sp. radicis-cucumerinum) on greenhouse cucumber. Dairy and
      greenhouse composts significantly reduced disease severity (P = 0.05), while Ball
      compost had no effect. Assessment of total culturable microbes in the composts
      showed a positive relationship between disease suppressive ability and total
      population levels of pseudomonads. In vitro antagonism assays between compost
      isolated bacterial strains and the pathogen showed that strains of Pseudomonas
      aeruginosa exhibited the greatest antagonism. In growth room trials, strains of
      P. aeruginosa and nonantagonistic Pseudomonas maculicola, plus 2 biocontrol
      strains of Pseudomonas fluorescens, were tested for their ability to reduce (i)
      survival of F. oxysporum, (ii) colonization of plants by the pathogen, and (iii)
      disease severity. Cucumber seedlings grown in compost receiving P. aeruginosa and
      P. fluorescens had reduced disease severity index scores after 8 weeks compared
      with control plants without bacteria. Internal stem colonization by F. oxysporum
      was significantly reduced by P. aeruginosa. The bacteria colonized plant roots at
      1.9 * 10(6) +/- 0.73 * 10(6) CFU.(g root tissue)-1 and survival was >107 CFU.(g
      compost)-1 after 6 weeks. The locus for 2,4-diacetylphloroglucinol production was
      detected by Southern blot analysis and confirmed by PCR. The production of the
      antibiotic 2,4-diacetylphloroglucinol in liquid culture by P. aeruginosa was
      confirmed by thin layer chromatography. These results demonstrate that composts
      containing antibiotic-producing P. aeruginosa have the potential to suppress
      diseases caused by Fusarium species.

PMID- 21076481
TI  - Verticillium dahliae alters Pseudomonas spp. populations and HCN gene expression
      in the rhizosphere of strawberry.
AB  - The production of hydrogen cyanide (HCN) by beneficial root-associated bacteria
      is an important mechanism for the biological control of plant pathogens. However,
      little is known about the biotic factors affecting HCN gene expression in the
      rhizosphere of plants. In this study, real-time reverse transcription PCR (qRT
      PCR) assays were developed to investigate the effect of the plant pathogen
      Verticillium dahliae on hcnC (encoding for HCN biosynthesis) gene expression in
      Pseudomonas sp. LBUM300. Strawberry plants were inoculated with Pseudomonas sp.
      LBUM300 and (or) V. dahliae and grown in pots filled with nonsterilized field
      soil. RNA was extracted from rhizosphere soil sampled at 0, 15, 30, and 45 days
      following inoculation with V. dahliae and used for qRT-PCR analyses. Populations
      of V. dahliae and Pseudomonas sp. LBUM300 were also monitored using a culture
      independent qPCR approach. hcnC expression was detected at all sampling dates.
      The presence of V. dahliae had a significant stimulation effect on hcnC gene
      expression and also increased the population of Pseudomonas sp. LBUM300. However,
      the V. dahliae population was not altered by the presence of Pseudomonas sp.
      LBUM300. To our knowledge, this study is the first to evaluate the effect of a
      plant pathogen on HCN gene expression in the rhizosphere soil.

PMID- 21076482
TI  - Hemolytic phospholipase Rv0183 of Mycobacterium tuberculosis induces inflammatory
      response and apoptosis in alveolar macrophage RAW264.7 cells.
AB  - The metabolic pathway of phospholipids is one of the most important physiologic
      pathways in Mycobacterium tuberculosis, a typical intracellular bacterium. The
      hemolytic phospholipase lip gene (Rv0183) is one of 24 phospholipase genes that
      have been demonstrated to play critical roles in the metabolism of phospholipids
      in M. tuberculosis. Quantitative RT-PCR and flow cytometry were used to elucidate
      the immunological and pathogenic implications of the Rv0183 gene on the
      inflammatory response following persistent expression of Rv0183 in mouse alveolar
      macrophage RAW264.7 cells. Our results demonstrate that a time-course-dependent
      ectopic expression of Rv0183 significantly elevated the expression of IL-6, NF
      kappaB, TLR-2, TLR-6, TNFalpha, and MyD88 in these alveolar macrophage cells.
      Furthermore, the persistent expression of Rv0183 induced RAW264.7 cell apoptosis
      in vitro. These findings demonstrate that the expression of Rv0183 induces an
      inflammatory response and cell apoptosis in the host cells, suggesting that
      Rv0183 may play an important role in the virulence and pathogenesis of M.
      tuberculosis infection.

PMID- 21076483
TI  - Classification of 17 newly isolated virulent bacteriophages of Pseudomonas
      aeruginosa.
AB  - Seventeen virulent bacteriophages specific to Pseudomonas aeruginosa strains were
      isolated by screening various environmental samples. These isolated
      bacteriophages were grouped based on results obtained from restriction fragment
      analysis of phage genomes, random amplification of polymorphic DNA (RAPD) typing,
      morphology observations under transmission electron microscope, and host range
      analysis. All 17 bacteriophages are double-stranded DNA viruses and can be
      divided into 5 groups based on DNA restriction profiles. A set of 10-mer primers
      was used in RAPD typing of phages, and similar conclusions were obtained as for
      restriction fragment analysis. One phage was randomly selected from each of the 5
      groups for morphology observations. Four of them had an icosahedral head with a
      long contractile tail, belonging to the Myoviridae family, and one phage had an
      icosahedral head with a short tail, thereby belonging to the Podoviridae family.
      Host range experiments were conducted on 7 laboratory strains and 12 clinical
      strains of P. aeruginosa. The results showed that 13 phages had the same
      infection profile, killing 8 out of 19 tested P. aeruginosa strains, and the
      remaining 4 phages had different and unique infection profiles. This study
      highlights the diversity of bacteriophages specific to P. aeruginosa in the
      environment.

PMID- 21076484
TI  - Characterization of a thioredoxin (BbTrx) from the entomopathogenic fungus
      Beauveria bassiana and its expression in response to thermal stress.
AB  - A thioredoxin (BbTrx) was identified from the entomopathogenic fungus Beauveria
      bassiana. The cloned nucleotide sequence consisted of a 423-bp open reading frame
      encoding a 141-amino-acid thioredoxin, a 1011-bp 5' region, and a 419-bp 3'
      region. The deduced protein sequence of BbTrx, including a common 95-amino-acid
      conserved domain and a unique 46-amino-acid carboxy terminal region, was similar
      (<=38% identity) to that of other thioredoxins and phylogenetically closest to
      that from Neurospora crassa. In insulin solution containing dithiothreitol at 25 
      degrees C, recombinant BbTrx or a truncated form lacking the carboxy terminal
      region (BbTrxD) exhibited disulfide reduction activity. BbTrxD was more active
      after pre-incubation at 40-75  degrees C, and cells expressing BbTrxD showed
      significantly higher tolerance to thermal stress (51  degrees C). The BbTrx
      expression in B. bassiana was greatly elevated when stressed at 40  degrees C.
      The results indicate that the new thioredoxin is a potential target for improving
      the thermotolerance of B. bassiana formulations.

PMID- 21076485
TI  - Comparison of microbial diversity of edible flowers and basil grown with organic
      versus conventional methods.
AB  - The consumption and use of edible flowers as food is growing; however, no study
      has been conducted to evaluate their role in the cause of food-borne illness or
      in food safety. Recent food-borne outbreaks traced to fresh herbs have raised
      concern about their processing and handling. Basil, one of the most commonly used
      fresh herbs, has been identified as a source of food-borne illness. Baseline
      assessments of microflora were performed, and the microbial diversity between
      growing methods (organic vs. conventional) was compared. DNA sequencing was used
      to identify the microbial flora present on fresh edible flower and basil samples.
      The most predominant species identified were Enterobacter hormaechei (10%),
      Acinetobacter calcoaceticus (10%), Enterobacter ludwigii (10%), Enterobacter
      asburiae (6%), and Enterobacter cowanii (6%). Pseudomonas aeruginosa (6%),
      Salmonella enterica (6%), and Bacillus amyloliquefaciens (2%) were also isolated.
      Phylogenetic analysis showed that most species of isolated bacteria belonged to
      the phyla Gammaproteobacteria (81.2%) and Firmicutes (18.8%). Statistical
      analysis, diversity index for species richness, and lineage-per-time plots showed
      that for basil, organically grown samples had a higher microbial diversity than
      conventionally grown samples. Edible flowers and basil are often grown using
      organic methods and are commonly consumed raw without any washing or cooking, to
      preserve aesthetic value, but these practices may pose a potential risk for food
      borne illness. The baseline assessment, together with phylogenetic and
      statistical analyses, indicated possible microbial contamination in edible
      flowers and basil. The use of statistical estimation of molecular diversity based
      on the 16S rRNA sequences and lineage-per-time plots with phylogenetic analysis
      well served as a means for comparing microbial diversity in food samples between
      the growing methods (organic vs. conventional).

PMID- 21076486
TI  - Effect of the cortex-lytic enzyme SleC from non-food-borne Clostridium
      perfringens on the germination properties of SleC-lacking spores of a food
      poisoning isolate.
AB  - The hallmark of bacterial spore germination is peptidoglycan cortex hydrolysis by
      cortex-lytic enzymes. In spores of Clostridium perfringens wild-type strain
      SM101, which causes food poisoning, the sole essential cortex-lytic enzyme SleC
      is activated by a unique serine protease CspB. Interestingly, the non-food-borne
      wild-type strain F4969 encodes a significantly divergent SleC variant (SleCF4969)
      and 3 serine proteases (CspA, CspB, and CspC). Consequently, in this study we
      evaluated the functional compatibility of SleCF4969 and SleCSM101 by
      complementing the germination phenotypes of SM101DeltasleC spores with sleCF4969.
      Our results show that although pro-SleCF4969 was processed into mature SleCF4969
      in the SM101DeltasleC spores, it partially restored spore germination with
      nutrient medium, with a mixture of L-asparagine and KCl, or with a 1:1 chelate of
      Ca2+ and dipicolinic acid. While the amount of dipicolinic acid released was
      lower, the amount of hexosamine-containing material released during germination
      of SM101DeltasleC(sleCF4969) spores was similar to the amount released during
      germination of SM101 wild-type spores. The viability of SM101DeltasleC(sleCF4969)
      spores was 8- and 3-fold lower than that of SM101 and F4969 spores, respectively.
      Together, these data indicate that the peptidoglycan cortex hydrolysis machinery
      in the food poisoning isolate SM101 is functionally divergent than that in the
      non-food-borne isolate F4969.

PMID- 21076487
TI  - Recombinant Porphyromonas gingivalis FimA preproprotein expressed in Escherichia
      coli is lipidated and the mature or processed recombinant FimA protein forms a
      short filament in vitro.
AB  - The gram-negative anaerobic bacterium Porphyromonas gingivalis is an
      etiologically important pathogen for chronic periodontal diseases in adults. Our
      previous study suggested that the major structural components of both Fim and Mfa
      fimbriae in this organism are secreted through their lipidated precursors. In
      this study, we constructed Escherichia coli strains expressing various fimA genes
      with or without the 5'-terminal DNA region encoding the signal peptide, and we
      determined whether lipidation of recombinant FimA proteins occurred in E. coli.
      Lipidation occurred for a recombinant protein from the fimA gene with the 5'
      terminal DNA region encoding the signal peptide but not for a recombinant protein
      from the fimA gene without the signal-peptide-encoding region, as revealed by
      [3H]palmitic acid labeling experiments. A TLR2-dependent signaling response was
      induced by the recombinant protein from the fimA gene with the signal-peptide
      encoding region but not by a recombinant protein from the fimA gene with the
      signal-peptide-encoding region that had a base substitution causing an amino acid
      substitution (C19A). Electron microscopic analysis revealed that recombinant FimA
      (A-47 - W-383) protein was autopolymerized to form filamentous structures of
      about 80 nm in length in vitro. The results suggest that FimA protein, a major
      subunit of Fim fimbriae, is transported to the outer membrane by the lipoprotein
      sorting system, and a mature or processed FimA protein on the outer membrane is
      autopolymerized to form Fim fimbriae.

PMID- 21076488
TI  - Microbiological quality of blue mussels (Mytilus edulis) in Nunavik, Quebec: a
      pilot study.
AB  - This pilot study was aimed at documenting the presence of fecal indicators and
      enteric pathogens in blue mussels (Mytilus edulis) from 6 communities in Nunavik,
      Quebec. One to four 2 kg samples of mussels were collected at low tide in each
      community. Samples were investigated by enumeration methods for the fecal
      indicators enterococci, Escherichia coli, F-specific coliphages, Clostridium
      perfringens, and by molecular identification for the pathogens norovirus,
      Salmonella spp., Campylobacter jejuni, Campylobacter coli, and Campylobacter
      lari, verocytotoxin-producing E. coli (particularly serovar O157:H7), Shigella
      spp., and Yersinia enterocolitica. In 5 communities, the presence of Giardia
      duodenalis and Cryptosporidium spp. was also tested by microscopy and molecular
      methods and that of Toxoplasma gondii was tested by molecular methods. Apart from
      small quantities of Clostridium perfringens in 2 samples, no bacterial or viral
      pathogens were detected in the mussels. Toxoplasma gondii was also not detected.
      However, G. duodenalis and Cryptosporidium spp. were present in 18% and 73% of
      the samples investigated for these pathogens, respectively. When considering the
      indicators and the viral and bacterial pathogens investigated, the mussels
      examined were of good microbiological quality, but considering the presence of
      potentially zoonotic protozoa, it should be recommended that consumers cook the
      molluscs well before eating them.

PMID- 21076489
TI  - Effects of Longevinex (modified resveratrol) on cardioprotection and its
      mechanisms of action.
AB  - Although resveratrol has been proven to possess diverse health benefits, several
      recent reports have demonstrated conflicting results on some aspects of its
      effects, including its anti-aging properties. Considerable debate appears to
      exist on the dose and bioavailability of resveratrol, leading to the
      controversies on its effectiveness. To resolve the problem, we designed a study
      with a resveratrol formulation that contained resveratrol supplemented with 5%
      quercetin and 5% rice bran phytate (commercially known as Longevinex). These
      ingredients were micronized to increase the bioavailability. Sprague-Dawley rats
      were gavaged with either Longevinex or vehicle (5% quercetin plus 5% rice bran
      phytate), and rats were sacrificed after 1 or 3 months, when isolated working
      hearts were subjected to 30 min ischemia followed by 2 h of reperfusion.
      Longevinex-treated hearts, irrespective of the duration of treatments, revealed
      superior cardiac performance, reduced infarct size, and induction of survival
      signals as evidenced by increased Bcl2/Bax ratio and enhanced Akt
      phosphorylation. In contrast, LC3-II and Beclin were enhanced significantly after
      3 months of Longevinex treatment, suggesting that autophagy occurred only after
      feeding Longevinex to rats for a prolonged period of time. Corroborating with the
      results of autophagy, Sirt1 and Sirt3 increased significantly only after 3 months
      of Longevinex treatment, suggesting that enhanced expression of Sirts correlated
      with induction of autophagy. In concert, Longevinex caused phosphorylation and
      nuclear translocation of FoxO1, FoxO3a, and FoxO4, indicating involvement of
      FoxOs with autophagy. Since Sirts and FoxOs are reliable markers of longevity,
      the results appear to suggest that Longevinex induces longevity after prolonged
      feeding via induction of autophagy, while it converts death signals into survival
      signals and provides cardioprotection within a relatively shorter period of time.

PMID- 21076490
TI  - Effect of simvastatin on collagen I deposition in non-infarcted myocardium: role
      of NF-kappaB and osteopontin.
AB  - The novel biological effect of statins in alleviating myocardium fibrosis
      following infarction has been increasingly recognized, yet the underlying
      mechanisms are not fully understood. The purpose of this study was to
      characterize the effect of simvastatin on myocardial fibrosis and collagen I
      deposition in the non-infarcted region after myocardial infarction (MI) and to
      identify the role of NF-kappaB and osteopontin in simvastatin-mediated inhibition
      of post-MI collagen over-expression. A rat model of MI was generated by ligating
      the left anterior descending coronary artery. The rats surviving the MI operation
      were randomly divided into the following 3 groups: myocardial infarction (MI,
      vehicle), simvastatin (Sim, 30 mg.kg-1.day-1), and pyrrolidine dithiocarbamate
      (PDTC, an inhibitor of NF-kappaB, 100 mg.kg-1.day-1). Four weeks after MI,
      cardiac function, mRNAs, and protein expression in non-infarcted myocardium were
      analyzed. Myocardial fibrosis and collagen I over-expression were observed
      following MI, accompanied by an increase of NF-kappaB and osteopontin.
      Simvastatin improved post-MI left ventricular dysfunction and ameliorated post-MI
      associated changes to several cardiac parameters, including the left ventricular
      end diastolic pressure (LVEDP), the maximal rate of pressure development
      (+dP/dtmax), and the maximal rate of pressure decline (-dP/dtmax). Concurrently,
      simvastatin significantly suppressed the over-expression of NF-kappaB,
      osteopontin, and collagen I in the non-infarcted region following MI. Inhibition
      of NF-kappaB by PDTC also reduced osteopontin over-expression and excessive
      collagen I production and improved the above functional myocardial parameters.
      These results show that post-MI myocardial fibrosis and collagen I over
      expression in the non-infarcted region is associated with activation of NF-kappaB
      and osteopontin up-regulation. The anti-fibrotic effect of simvastatin following
      MI is associated with the attenuation of the expression of osteopontin and NF
      kappaB. The inhibition of NF-kappaB activation could be the process upstream of
      osteopontin suppression in the simvastatin-mediated effect.

PMID- 21076491
TI  - Differential constrictor responses of cephalic and caudal vasculature to alpha
      adrenoceptor agonist after hind limb unloading.
AB  - We examined the effects of hind limb unloading (HLU, 14 days) on constriction of
      carotid and iliac arterial beds in vivo in thiobutabarbital-anaesthetized rats
      and isolated carotid and iliac arteries in vitro. Both control and HLU rats had
      similar arterial pressure and carotid and iliac arterial flows. The HLU rats had
      increased carotid arterial but reduced iliac arterial constriction in response to
      methoxamine (alpha1-adrenoceptor agonist) in vivo. In contrast, constriction in
      response to methoxamine was reduced in the isolated carotid and unchanged in the
      iliac artery of HLU rats relative to control rats. Thus, HLU is associated with
      increased constriction of carotid arterial bed but reduced constriction of the
      isolated carotid artery, and reduced constriction of iliac arterial bed but
      unchanged constriction of the isolated iliac artery. These results show
      differential influence of HLU on constriction of cephalic and caudal arterial
      beds, and differential effect on constrictions of arterial beds relative to
      conduit arteries.

PMID- 21076492
TI  - Ipomoea obscura ameliorates cyclophosphamide-induced toxicity by modulating the
      immune system and levels of proinflammatory cytokine and GSH.
AB  - Ipomoea obscura L. is a widely used medicinal plant. The objective of this study
      was to investigate its protective activity against cyclophosphamide (CTX)-induced
      toxicity in mouse models. Swiss albino mice were treated intraperitoneally with
      CTX (25 mg/kg body weight) along with I. obscura extract (10 mg/kg body weight)
      for 10 days. Extract significantly reduced myelosuppression caused by CTX and
      improved the relative organ weight, total white blood cell count, and bone marrow
      cellularity. The elevated levels of parameters related to pathophysiology of the
      liver, namely glutamate pyruvate transaminase, alkaline phosphatase, and lipid
      peroxidation, were significantly reduced by extract treatment. Reduction of liver
      and intestinal glutathione levels of CTX-treated animals was reversed by I.
      obscura. The lowered levels of cytokines, namely IFN-gamma, IL-2, and granulocyte
      monocyte colony-stimulating factor after CTX treatment were found to be increased
      in I. obscura treated animals. Treatment with I. obscura could also decrease the
      level of proinflammatory cytokine TNF-alpha. The data suggested that I. obscura
      can act as a potent chemoprotective agent and can be used as an adjuvant in
      chemotherapeutic applications.

PMID- 21076493
TI  - Effects of low-dose ketanserin on atherosclerosis in rats and rabbits.
AB  - The present study was designed to test the hypothesis that a small dose of
      ketanserin, which enhances baroreflex activity, prevents the early lesions of
      atherosclerosis. In experiment 1, baroreflex sensitivity (BRS) was measured in 31
      spontaneously hypertensive rats (SHRs) in a conscious state using a computerized
      blood pressure monitoring system. Four weeks later, the rats were administered
      vitamin D3 and fed a high-cholesterol diet for 8 weeks to induce atherosclerosis.
      Then their hearts and aortae were removed for pathological examination. A
      negative correlation was found between BRS and the scores of coronary (r = 
      0.460, P < 0.01) and aortic atherosclerosis (r = -0.448, P < 0.05) in SHR. In
      experiment 2, SHRs were divided into 3 groups (n = 10 in each group) and received
      a dose of ketanserin of 0.3, 1.0, and 3.0 mg/kg (i.g.), respectively. At the
      smallest dose (0.3 mg/kg), ketanserin did not lower blood pressure but enhanced
      BRS. In experiment 3, SHRs were administered vitamin D3, fed a high-cholesterol
      diet, and simultaneously treated with low-dose ketanserin. The atherosclerosis
      scores of the treatment group were significantly lower than those of the control
      group (coronary score: 0.90 +/- 0.14 vs. 1.76 +/- 0.27, P < 0.05; aortic scores:
      1.00 +/- 0.39 vs. 2.18 +/- 0.41, P < 0.05). In experiment 4, male New Zealand
      White rabbits were fed a high-cholesterol diet and treated with low-dose
      ketanserin at the same time. The atherosclerosis scores of the treatment group
      were significantly lower than those of the control group (aortic scores: 0.26 +/-
      0.20 vs. 0.60 +/- 0.31, P < 0.05). In conclusion, the present study demonstrated,
      for the first time, that low-dose ketanserin prevented the development of
      atherosclerosis independent of its blood pressure lowering action in SHRs and New
      Zealand White rabbits at least in part via enhancement of arterial baroreflex
      function.

PMID- 21076494
TI  - The influence of affinity, efficacy, and slope factor on the estimates obtained
      by the receptorial responsiveness method (RRM): a computer simulation study.
AB  - The receptorial responsiveness method (RRM) was proposed to characterize changes
      in the concentration of degradable agonists in the microenvironment of their
      receptors. The characterization is done by providing concentrations of a stable
      agonist for the same receptor that is equieffective with the change in
      concentration to be characterized. RRM is based on the analysis of concentration
      effect (E/c) curves reflecting the simultaneous action of the degradable and the
      stable agonist. In the present study, we investigated whether dissimilar affinity
      and (or) efficacy of the coacting agonists as well as the steepness of the E/c
      curves influence the reliability of RRM. E/c curves were simulated based on the
      operational model and then analyzed with RRM. We found that dissimilarity in
      affinity of the coacting agonists did not affect the accuracy of RRM estimates.
      In contrast, accuracy of the estimation depended on the magnitude of the
      concentration to be assessed, the operational slope factor, and the operational
      efficacy ratio of the coacting agonists. However, our results suggest that proper
      choice of a stable agonist for a degradable one can help to ensure reliable
      results, since information about the change in concentration of a degradable
      agonist is otherwise difficult to obtain.

PMID- 21076495
TI  - Effect of asymmetry of concentration-response curves on the results obtained by
      the receptorial responsiveness method (RRM): an in silico study.
AB  - The receptorial responsiveness method (RRM) was proposed to estimate changes in
      the concentration of an agonist in the microenvironment of its receptor. Usually,
      this is done by providing the equieffective concentration of another agonist for
      the same receptor or for a largely overlapping postreceptorial signaling ("test
      agonist"). The RRM is a special nonlinear regression algorithm to analyze a
      concentration-response (E/c) curve that represents the simultaneous actions of a
      single agonist concentration to be estimated and of increasing concentrations of
      the test agonist. The aim of this study was to explore whether asymmetry of the
      E/c curve to be analyzed influences the reliability of the RRM. For this purpose,
      computer simulation was performed by constructing symmetric and asymmetric E/c
      curves using the operational model of agonism, and then these curves were
      analyzed with the RRM. To perform the RRM, 2 types of equations were used: one
      involving the Hill equation, the simplest model of the E/c relationship, and one
      containing the Richards equation, an advanced model properly handling E/c curve
      asymmetry. Results of this study indicate that E/c curve asymmetry does not
      significantly influence the accuracy of the estimates provided by the RRM. Thus,
      when using the RRM, it is not necessary to replace the Hill equation with the
      Richards equation to obtain useful estimates. Furthermore, it was found that
      estimation of a high concentration of a high-efficacy agonist can fail when the
      RRM is performed with a low-efficacy test agonist in a system characterized by a
      small operational slope factor.

PMID- 21076496
TI  - Regulation of stress-associated scaffold proteins JIP1 and JIP3 on the c-Jun NH2
      terminal kinase in ischemia-reperfusion.
AB  - Ischemia-reperfusion (IR)-induced cell apoptosis involves the activation of c-Jun
      NH2-terminal kinase (JNK). The activation of JNK requires the presence of
      scaffold proteins called JNK-interacting proteins (JIP), which bind several
      members of a signaling cascade for proper signaling specificity. In this study,
      the expression of scaffold proteins JIP1 and JIP3 and their roles in the
      regulation of JNK activity were investigated in simulated IR in a cell model
      (H9c2). JIP1 protein expression was significantly decreased, whereas JIP3 protein
      expression was increased in IR H9c2 cells. Adenovirus-induced overexpression of
      JIP1 reduced IR-induced JNK activity and apoptosis. Conversely, overexpression of
      JIP3 increased JNK activity and apoptosis following IR. Depletion of endogenous
      JIP1 by siRNA treatment increased the IR-induced JNK activity, whereas siRNA
      mediated depletion of endogenous JIP3 inhibited JNK activity. These results
      suggest that JIP1 and JIP3 play important roles in the activation of JNK during
      simulated IR challenge in H9c2 cells.

PMID- 21076497
TI  - Sequential alterations in Akt, GSK3beta, and calcineurin signalling in the mouse
      left ventricle after thoracic aortic constriction.
AB  - Left ventricular hypertrophy (LVH) is an adaptive response to chronic
      biomechanical stress that generally progresses to maladaptive hypertrophy and
      heart failure (HF). We studied the activation of protein kinase B (Akt/PKB),
      glycogen synthase kinase 3 beta (GSK3beta), and calcineurin (Cn) at 3, 7, 15, 30,
      and 60 days following transverse aortic constriction (TAC) in 4-week-old mice.
      Following TAC, GSK3beta inactivation at day 3 was associated with Akt activation,
      whereas at days 15 and 30, it appeared to be controlled by other kinases.
      Moderate nonsignificant Cn activation occurred at the early stages, and peak
      activation at day 30, concomitant with GSK3beta inactivation and overt LVH and
      HF. At the latest stage (day 60), despite further progression of LVH and HF, Cn
      activation appeared attenuated. Early stages of LVH were associated with Ca2+
      handling protein upregulation, whereas major Cn activation, associated with
      GSK3beta inactivation, appeared to engage maladaptive hypertrophy and progression
      to HF associated with Ca2+-handling protein downregulation.

PMID- 21076498
TI  - Chloroethyl urea derivatives block tumour growth and thioredoxin-1 nuclear
      translocation.
AB  - Aryl chloroethyl ureas (CEUs) are new protein alkylating agents exhibiting
      anticancer activity both in vitro and in vivo. We report herein that 14C-labeled
      CEU derivatives, designated CEU-025 and CEU-027, covalently bind to thioredoxin-1
      (TRX1). Covalent binding of these molecules slightly decreases the disulfide
      reducing activity of recombinant TRX1, when compared with the effect of strong
      thioalkylating agents such as N-ethylmaleimide. Moreover, site-directed
      mutagenesis and diamide competition assays demonstrated that TRX1 cysteinyl
      residues are not the prime targets of CEUs. CEU-025 abrogates the nuclear
      translocation of TRX1 in human cancer cells. In addition, we show that CEU-025
      can block TRX1 nuclear translocation induced by cisplatin. Unexpectedly,
      pretreatment with sublethal CEU-025 concentrations that block TRX1 nuclear
      translocation protected the cells against cisplatin cytotoxicity. Overexpression
      of TRX1 in HT1080 fibrosarcoma cells attenuated CEU-025 cytotoxicity, while its
      suppression using TRX1-specific siRNA increased the effects of CEU-025,
      suggesting that loss of function of TRX1 is involved, at least in part, in the
      cytotoxic activity of CEU-025. These results suggest that CEU-025 and CEU-027
      exhibit anticancer activity through a novel, unique mechanism of action. The
      importance of TRX1 and the dependence of the cytotoxicity of CEU-025 and CEU-027
      on TRX1 intracellular localization are also discussed.

PMID- 21076499
TI  - Caffeine-induced natriuresis and diuresis via blockade of hepatic adenosine
      mediated sensory nerves and a hepatorenal reflex.
AB  - The hepatorenal reflex, activated by intrahepatic adenosine, is involved in the
      regulation of urine production in healthy rats and renal pathogenesis secondary
      to liver injury. Hepatic adenosine A1 receptors regulate the hepatorenal reflex.
      The aim of the present study was to evaluate whether caffeine mediates renal
      natriuresis and diuresis in healthy and diseased liver through this mechanism.
      Rats were anesthetized and instrumented to monitor systemic, hepatic, and renal
      circulation and urine production. Intrahepatic (intraportal but not intravenous)
      caffeine (5 mg.kg-1) increased urine flow (~82%) in healthy rats. This effect was
      abolished by liver denervation. Intraportal infusion of adenosine decreased urine
      production, and this response was abolished by intraportal but not intravenous
      caffeine. Liver injury was induced by intraperitoneal injection of thioacetamide
      (500 mg.kg-1), and functional assessment was performed 24 h later. Liver injury
      was associated with lower (~30%) glomerular filtration rate, lower (~18%) renal
      arterial blood flow, and lower urine production. Intraportal but not intravenous
      caffeine improved basal urine production and renal ability to increase urine
      production in response to saline overload. The liver-dependent diuretic effect of
      caffeine is consistent with the hypothesis for the adenosine-mediated mechanism
      of hepatorenal syndrome.

PMID- 21076500
TI  - Exploiting genome-wide association in oilseed Brassica species.

PMID- 21076501
TI  - Exploring and exploiting epigenetic variation in crops.
AB  - This review addresses the mechanisms by which epigenetic variation modulates
      plant gene regulation and phenotype. In particular we explore the scope for
      harnessing such processes within the context of crop genetic improvement. We
      focus on the role of DNA methylation as an epigenetic mark that contributes to
      epiallelic diversity and modulation of gene regulation. We outline the prevalence
      and distribution of epigenetic marks in relation to eukaryote developmental
      processes, and in particular identify where this may be relevant to crop traits
      both in terms of specific developmental stages and in relation to physiological
      responses to environmental change. Recent whole genome surveys have identified
      specific characteristics of the distribution of DNA methylation within plant
      genomes. Together with greater understanding of the mode of action of different
      maintenance and de novo methyltransferases, this provides an opportunity to
      modulate DNA methylation status at specific loci as an intervention strategy in
      crop genetic improvement. We discuss alternative approaches that may be suitable
      for harnessing such induced epiallelic variation. Most of the discussion is
      associated with Brassica crops, which demonstrate considerable morphological
      plasticity, segmental chromosomal duplication, and polyploidy.

PMID- 21076503
TI  - Genome-wide association and genomic selection in animal breeding.
AB  - Results from genome-wide association studies in livestock, and humans, has lead
      to the conclusion that the effect of individual quantitative trait loci (QTL) on
      complex traits, such as yield, are likely to be small; therefore, a large number
      of QTL are necessary to explain genetic variation in these traits. Given this
      genetic architecture, gains from marker-assisted selection (MAS) programs using
      only a small number of DNA markers to trace a limited number of QTL is likely to
      be small. This has lead to the development of alternative technology for using
      the available dense single nucleotide polymorphism (SNP) information, called
      genomic selection. Genomic selection uses a genome-wide panel of dense markers so
      that all QTL are likely to be in linkage disequilibrium with at least one SNP.
      The genomic breeding values are predicted to be the sum of the effect of these
      SNPs across the entire genome. In dairy cattle breeding, the accuracy of genomic
      estimated breeding values (GEBV) that can be achieved and the fact that these are
      available early in life have lead to rapid adoption of the technology. Here, we
      discuss the design of experiments necessary to achieve accurate prediction of
      GEBV in future generations in terms of the number of markers necessary and the
      size of the reference population where marker effects are estimated. We also
      present a simple method for implementing genomic selection using a genomic
      relationship matrix. Future challenges discussed include using whole genome
      sequence data to improve the accuracy of genomic selection and management of
      inbreeding through genomic relationships.

PMID- 21076502
TI  - Statistical genetic issues for genome-wide association studies.
AB  - Genotyping technology now allows the rapid and affordable generation of million
      SNP profiles for humans, leading to considerable activity in association mapping.
      Similar activity is anticipated for many plant species, including Brassica. These
      plant association mapping activities will require the same care in quality
      control and quality assurance as for humans. The subsequent analyses may draw
      upon the same body of theory that is described here in the language of
      quantitative genetics.

PMID- 21076504
TI  - Design of a Brassica rapa core collection for association mapping studies.
AB  - A Brassica rapa collection of 239 accessions, based on two core collections
      representing different morphotypes from different geographical origins, is
      presented and its use for association mapping is illustrated for flowering time.
      We analyzed phenotypic variation of leaf and seed pod traits, plant architecture,
      and flowering time using data collected from three field experiments and
      evaluated the genetic diversity with a set of SSR markers. The Wageningen
      University and Research Centre (WUR) and the Vavilov Research Institute of Plant
      Industry (VIR) core collections had similar representations of most morphotypes,
      as illustrated by the phenotypic and genetic variation within these groups. The
      analysis of population structure revealed five subgroups in the collection,
      whereas previous studies of the WUR core collection indicated four subgroups; the
      fifth group identified consisted mainly of oil accessions from the VIR core
      collection, winter oils from Pakistan, and a number of other types. A very small
      group of summer oils is described, that is not related to other oil accessions. A
      candidate gene approach was chosen for association mapping of flowering time with
      a BrFLC1 biallelic CAPS marker and a BrFLC2 multiallelic SSR marker. The two
      markers were significantly associated with flowering time, but their effects were
      confined to certain morphotypes and (or) alleles. Based on these results, we
      discuss the optimal design for an association mapping population and the need to
      fix the heterogeneous accessions to facilitate phenotyping and genotyping.

PMID- 21076505
TI  - Association mapping for phenological, morphological, and quality traits in canola
      quality winter rapeseed (Brassica napus L.).
AB  - QTL mapping by association analysis has recently gained interest in plant
      breeding research as an alternative to QTL mapping in segregating populations
      from biparental crosses. In a first experiment on whole-genome association
      analysis in rapeseed, 684 mapped AFLP markers were tested for association with 14
      traits in a set of 84 canola quality winter rapeseed cultivars. For association
      analysis a general linear model was used. By testing significance of marker-trait
      associations against a false discovery rate of 0.2, between 1 and 34 associated
      markers were found for 10 of the 14 traits. Taking into account linkage
      disequilibrium between the significant markers, these markers represent between 1
      and 22 putative QTL for the respective traits. The minimum phenotypic variance
      explained by the QTL for the different traits ranged from 15% to 53%. A subset of
      27 markers were significantly associated with two or more traits. These markers
      were predominantly shared between traits that were significantly correlated at
      the phenotypic level. The results show clearly that in rapeseed, QTL mapping by
      association analysis is a viable alternative to QTL mapping in segregating
      populations.

PMID- 21076506
TI  - Association mapping of seed oil content in Brassica napus and comparison with
      quantitative trait loci identified from linkage mapping.
AB  - Association mapping has been used increasingly in natural populations with rich
      genetic diversity to detect DNA-based markers that are associated with important
      agronomic traits. Brassica napus is an important oil crop with limited genetic
      diversity. "New-type" B. napus that is introgressed with subgenomic components
      from related species has been developed to broaden the genetic basis of
      "traditional" B. napus. In this study, new-type B. napus lines and a collection
      of traditional B. napus varieties from different countries were used as two
      different populations to evaluate seed oil content and to determine the efficacy
      of association mapping by comparison with previous study of linkage mapping.
      Relatively rich genetic diversity, but a higher level of linkage disequilibrium
      was observed in the new-type B. napus as compared with the traditional B. napus.
      Similarly, a larger variation in oil content and a greater number of associated
      markers were detected in the population of new-type B. napus. Meanwhile, more
      than half of the genetic loci, to which the associated markers corresponded, were
      located within the quantitative trait loci intervals identified previously in
      linkage mapping experiments, which demonstrated the power of association mapping
      in B. napus.

PMID- 21076507
TI  - Regional association analysis delineates a sequenced chromosome region
      influencing antinutritive seed meal compounds in oilseed rape.
AB  - This study describes the use of regional association analyses to delineate a
      sequenced region of a Brassica napus chromosome with a significant effect on
      antinutritive seed meal compounds in oilseed rape. A major quantitative trait
      locus (QTL) influencing seed colour, fibre content, and phenolic compounds was
      mapped to the same position on B. napus chromosome A9 in biparental mapping
      populations from two different yellow-seeded * black-seeded B. napus crosses.
      Sequences of markers spanning the QTL region identified synteny to a sequence
      contig from the corresponding chromosome A9 in Brassica rapa. Remapping of
      sequence-derived markers originating from the B. rapa sequence contig confirmed
      their position within the QTL. One of these markers also mapped to a seed colour
      and fibre QTL on the same chromosome in a black-seeded * black-seeded B. napus
      cross. Consequently, regional association analysis was performed in a genetically
      diverse panel of dark-seeded, winter-type oilseed rape accessions. For this we
      used closely spaced simple sequence repeat (SSR) markers spanning the sequence
      contig covering the QTL region. Correction for population structure was performed
      using a set of genome-wide SSR markers. The identification of QTL-derived markers
      with significant associations to seed colour, fibre content, and phenolic
      compounds in the association panel enabled the identification of positional and
      functional candidate genes for B. napus seed meal quality within a small segment
      of the B. rapa genome sequence.

PMID- 21076508
TI  - Towards unambiguous transcript mapping in the allotetraploid Brassica napus.
AB  - The architecture of the Brassica napus genome is marked by its evolutionary
      origins. The genome of B. napus was formed from the hybridization of two closely
      related diploid Brassica species, both of which evolved from an hexaploid
      ancestor. The extensive whole genome duplication events in its near and distant
      past result in the allotetraploid genome of B. napus maintaining multiple copies
      of most genes, which predicts a highly complex and redundant transcriptome that
      can confound any expression analyses. A stringent assembly of 142,399 B. napus
      expressed sequence tags allowed the development of a well-differentiated set of
      reference transcripts, which were used as a foundation to assess the efficacy of
      available tools for identifying and distinguishing transcripts in B. napus;
      including microarray hybridization and 3' anchored sequence tag capture.
      Microarray platforms cannot distinguish transcripts derived from the two
      progenitors or close homologues, although observed differential expression
      appeared to be biased towards unique transcripts. The use of 3' capture enhanced
      the ability to unambiguously identify homologues within the B. napus
      transcriptome but was limited by tag length. The ability to comprehensively
      catalogue gene expression in polyploid species could be transformed by the
      application of cost-efficient next generation sequencing technologies that will
      capture millions of long sequence tags.

PMID- 21076509
TI  - Development of a high density integrated reference genetic linkage map for the
      multinational Brassica rapa Genome Sequencing Project.
AB  - We constructed a high-density Brassica rapa integrated linkage map by combining a
      reference genetic map of 78 doubled haploid lines derived from Chiifu-401-42 *
      Kenshin (CKDH) and a new map of 190 F2 lines derived from Chiifu-401-42 * rapid
      cycling B. rapa (CRF2). The integrated map contains 1017 markers and covers
      1262.0 cM of the B. rapa genome, with an average interlocus distance of 1.24 cM.
      High similarity of marker order and position was observed among the linkage
      groups of the maps with few short-distance inversions. In total, 155 simple
      sequence repeat (SSR) markers, anchored to 102 new bacterial artificial
      chromosomes (BACs) and 146 intron polymorphic (IP) markers were mapped in the
      integrated map, which would be helpful to align the sequenced BACs in the ongoing
      multinational Brassica rapa Genome Sequencing Project (BrGSP). Further,
      comparison of the B. rapa consensus map with the 10 B. juncea A-genome linkage
      groups by using 98 common IP markers showed high-degree colinearity between the A
      genome linkage groups, except for few markers showing inversion or translocation.
      Suggesting that chromosomes are highly conserved between these Brassica species,
      although they evolved independently after divergence. The sequence information
      coming out of BrGSP would be useful for B. juncea breeding. and the identified
      Arabidopsis chromosomal blocks and known quantitative trait loci (QTL)
      information of B. juncea could be applied to improve other Brassica crops
      including B. rapa.

PMID- 21076510
TI  - SNP discovery by amplicon sequencing and multiplex SNP genotyping in the
      allopolyploid species Brassica napus.
AB  - Oilseed rape (Brassica napus) is an allotetraploid species consisting of two
      genomes, derived from B. rapa (A genome) and B. oleracea (C genome). The presence
      of these two genomes makes single nucleotide polymorphism (SNP) marker
      identification and SNP analysis more challenging than in diploid species, as for
      a given locus usually two versions of a DNA sequence (based on the two ancestral
      genomes) have to be analyzed simultaneously during SNP identification and
      analysis. One hundred amplicons derived from expressed sequence tag (ESTs) were
      analyzed to identify SNPs in a panel of oilseed rape varieties and within two
      sister species representing the ancestral genomes. A total of 604 SNPs were
      identified, averaging one SNP in every 42 bp. It was possible to clearly
      discriminate SNPs that are polymorphic between different plant varieties from
      SNPs differentiating the two ancestral genomes. To validate the identified SNPs
      for their use in genetic analysis, we have developed Illumina GoldenGate assays
      for some of the identified SNPs. Through the analysis of a number of oilseed rape
      varieties and mapping populations with GoldenGate assays, we were able to
      identify a number of different segregation patterns in allotetraploid oilseed
      rape. The majority of the identified SNP markers can be readily used for genetic
      mapping, showing that amplicon sequencing and Illumina GoldenGate assays can be
      used to reliably identify SNP markers in tetraploid oilseed rape and to convert
      them into successful SNP assays that can be used for genetic analysis.

PMID- 21076511
TI  - Genome-wide association analyses of common wheat (Triticum aestivum L.) germplasm
      identifies multiple loci for aluminium resistance.
AB  - Aluminium (Al3+) toxicity restricts productivity and profitability of wheat
      (Triticum aestivum L.) crops grown on acid soils worldwide. Continued gains will
      be obtained by identifying superior alleles and novel Al3+ resistance loci that
      can be incorporated into breeding programs. We used association mapping to
      identify genomic regions associated with Al3+ resistance using 1055 accessions of
      common wheat from different geographic regions of the world and 178 polymorphic
      diversity arrays technology (DArT) markers. Bayesian analyses based on genetic
      distance matrices classified these accessions into 12 subgroups. Genome-wide
      association analyses detected markers that were significantly associated with
      Al3+ resistance on chromosomes 1A, 1B, 2A, 2B, 2D, 3A, 3B, 4A, 4B, 4D, 5B, 6A,
      6B, 7A, and 7B. Some of these genomic regions correspond to previously identified
      loci for Al3+ resistance, whereas others appear to be novel. Among the markers
      targeting TaALMT1 (the major Al3+-resistance gene located on chromosome 4D),
      those that detected alleles in the promoter explained most of the phenotypic
      variance for Al3+ resistance, which is consistent with this region controlling
      the level of TaALMT1 expression. These results demonstrate that genome-wide
      association mapping cannot only confirm known Al3+-resistance loci, such as those
      on chromosomes 4D and 4B, but they also highlight the utility of this technique
      in identifying novel resistance loci.

PMID- 21076512
TI  - Whole-genome association mapping in elite inbred crop varieties.
AB  - We have previously shown that linkage disequilibrium (LD) in the elite cultivated
      barley (Hordeum vulgare) gene pool extends, on average, for <1-5 cM. Based on
      this information, we have developed a platform for whole genome association
      studies that comprises a collection of elite lines that we have characterized at
      3060 genome-wide single nucleotide polymorphism (SNP) marker loci. Interrogating
      this data set shows that significant population substructure is present within
      the elite gene pool and that diversity and LD vary considerably across each of
      the seven barley chromosomes. However, we also show that a subpopulation
      comprised of only the two-rowed spring germplasm is less structured and well
      suited to whole genome association studies without the need for extensive
      statistical intervention to account for structure. At the current marker density,
      the two-rowed spring population is suited for fine mapping simple traits that are
      located outside of the genetic centromeres with a resolution that is sufficient
      for candidate gene identification by exploiting conservation of synteny with
      fully sequenced model genomes and the emerging barley physical map.

PMID- 21076513
TI  - Simultaneously accounting for population structure, genotype by environment
      interaction, and spatial variation in marker-trait associations in sugarcane.
AB  - Few association mapping studies have simultaneously accounted for population
      structure, genotype by environment interaction (GEI), and spatial variation. In
      this sugarcane association mapping study we tested models accounting for these
      factors and identified the impact that each model component had on the list of
      markers declared as being significantly associated with traits. About 480
      genotypes were evaluated for cane yield and sugar content at three sites and
      scored with DArT markers. A mixed model was applied in analysis of the data to
      simultaneously account for the impacts of population structure, GEI, and spatial
      variation within a trial. Two forms of the DArT marker data were used in the
      analysis: the standard discrete data (0, 1) and a continuous DArT score, which is
      related to the marker dosage. A large number of markers were significantly
      associated with cane yield and sugar content. However, failure to account for
      population structure, GEI, and (or) spatial variation produced both type I and
      type II errors, which on the one hand substantially inflated the number of
      significant markers identified (especially true for failing to account for GEI)
      and on the other hand resulted in failure to detect markers that could be
      associated with cane yield or sugar content (especially when failing to account
      for population structure). We concluded that association mapping based on trials
      from one site or analysis that failed to account for GEI would produce many trial
      specific associated markers that would have low value in breeding programs.

PMID- 21076514
TI  - Generating and maintaining diversity at the elite level in crop breeding.
AB  - Most breeding programs develop elite genotypes that are well adapted to the
      normal range of environmental conditions in the target production region. These
      elite lines have similar essential alleles for desirable end use characteristics,
      agronomics, disease resistance, and adaptation in the target region. The genetic
      makeup of these elite lines is complex. Intermating among the elite lines will
      often produce new variability through recombination with minimal risk of
      introducing new undesirable features, and is the source of most new cultivars.
      Eventually, this variation will be exhausted and new alleles must be introduced
      into the elite breeding population. Introducing desirable alleles from exotic
      germplasm may "pollute" the elite gene pool with undesirable alleles. Exotic
      germplasm may also disrupt essential allele combinations for adaptation, quality,
      and agronomic performance. New desirable alleles from exotic germplasm can be
      introgressed into an elite population in a systematic way through limited
      backcrossing with a minimal disturbance to the finely tuned elite background.
      Combining recurrent selection within elite germplasm with a systematic
      introgression from exotic germplasm in the recurrent introgressive population
      enrichment (RIPE) system has created an open-ended, continually improving, and
      sustainable elite population breeding system, which is simple, effective, and a
      regular source of new cultivars.

PMID- 21076515
TI  - Analysis of yield and oil from a series of canola breeding trials. Part I.
      Fitting factor analytic mixed models with pedigree information.
AB  - In this paper multiplicative mixed models have been used for the analysis of
      multi-environment trial (MET) data for canola oil and grain yield. Information on
      pedigrees has been included to allow for the modelling of additive and
      nonadditive genetic effects. The MET data set included a total of 19 trials
      (synonymous with sites or environments), which were sown across southern
      Australia in 2007 and 2008. Each trial was designed as a p-rep design using
      DiGGeR with the default prespecified spatial model. Lines in their first year of
      testing were unreplicated, whereas there were two or three replications of
      advanced lines or varieties. Pedigree information on a total of 578 entries was
      available, and there were 69 entries that had unknown pedigrees. The degree of
      inbreeding varied from 0 (55 entries) to nearly fully inbred (337 entries).
      Subsamples of 2 g harvested grain were taken from each plot for determination of
      seed oil percentage by near infrared reflectance spectroscopy. The MET analysis
      for both yield and oil modelled genetic effects in different trials using factor
      analytic models and the residual plot effects for each trial were modelled using
      spatial techniques. Models in which pedigree information was included provided
      significantly better fits to both yield and oil data.

PMID- 21076516
TI  - Analysis of yield and oil from a series of canola breeding trials. Part II.
      Exploring variety by environment interaction using factor analysis.
AB  - Exploring and exploiting variety by environment (V * E) interaction is one of the
      major challenges facing plant breeders. In paper I of this series, we presented
      an approach to modelling V * E interaction in the analysis of complex multi
      environment trials using factor analytic models. In this paper, we develop a
      range of statistical tools which explore V * E interaction in this context. These
      tools include graphical displays such as heat-maps of genetic correlation
      matrices as well as so-called E-scaled uniplots that are a more informative
      alternative to the classical biplot for large plant breeding multi-environment
      trials. We also present a new approach to prediction for multi-environment trials
      that include pedigree information. This approach allows meaningful selection
      indices to be formed either for potential new varieties or potential parents.

PMID- 21076518
TI  - Prospects and challenges for genome-wide association and genomic selection in
      oilseed Brassica species.

PMID- 21076517
TI  - Future tools for association mapping in crop plants.
AB  - Association mapping currently relies on the identification of genetic markers.
      Several technologies have been adopted for genetic marker analysis, with single
      nucleotide polymorphisms (SNPs) being the most popular where a reasonable
      quantity of genome sequence data are available. We describe several tools we have
      developed for the discovery, annotation, and visualization of molecular markers
      for association mapping. These include autoSNPdb for SNP discovery from assembled
      sequence data; TAGdb for the identification of gene specific paired read Illumina
      GAII data; CMap3D for the comparison of mapped genetic and physical markers; and
      BAC and Gene Annotator for the online annotation of genes and genomic sequences.

PMID- 21076519
TI  - Evidence for equilibrium iron isotope fractionation by nitrate-reducing iron(II)
      oxidizing bacteria.
AB  - Iron isotope fractionations produced during chemical and biological Fe(II)
      oxidation are sensitive to the proportions and nature of dissolved and solid
      phase Fe species present, as well as the extent of isotopic exchange between
      precipitates and aqueous Fe. Iron isotopes therefore potentially constrain the
      mechanisms and pathways of Fe redox transformations in modern and ancient
      environments. In the present study, we followed in batch experiments Fe isotope
      fractionations between Fe(II)(aq) and Fe(III) oxide/hydroxide precipitates
      produced by the Fe(III) mineral encrusting, nitrate-reducing, Fe(II)-oxidizing
      Acidovorax sp. strain BoFeN1. Isotopic fractionation in (56)Fe/(54)Fe approached
      that expected for equilibrium conditions, assuming an equilibrium
      Delta(56)Fe(Fe(OH)3 - Fe(II)aq) fractionation factor of +3.0 0/00. Previous
      studies have shown that Fe(II) oxidation by this Acidovorax strain occurs in the
      periplasm, and we propose that Fe isotope equilibrium is maintained through redox
      cycling via coupled electron and atom exchange between Fe(II)(aq) and Fe(III)
      precipitates in the contained environment of the periplasm. In addition to the
      apparent equilibrium isotopic fractionation, these experiments also record the
      kinetic effects of initial rapid oxidation, and possible phase transformations of
      the Fe(III) precipitates. Attainment of Fe isotope equilibrium between Fe(III)
      oxide/hydroxide precipitates and Fe(II)(aq) by neutrophilic, Fe(II)-oxidizing
      bacteria or through abiologic Fe(II)(aq) oxidation is generally not expected or
      observed, because the poor solubility of their metabolic product, i.e. Fe(III),
      usually leads to rapid precipitation of Fe(III) minerals, and hence expression of
      a kinetic fractionation upon precipitation; in the absence of redox cycling
      between Fe(II)(aq) and precipitate, kinetic isotope fractionations are likely to
      be retained. These results highlight the distinct Fe isotope fractionations that
      are produced by different pathways of biological and abiological Fe(II)
      oxidation.

PMID- 21076520
TI  - Inverse fourier transform in the gamma coordinate system.
AB  - This paper provides auxiliary results for our general scheme of computed
      tomography. In 3D parallel-beam geometry, we first demonstrate that the inverse
      Fourier transform in different coordinate systems leads to different
      reconstruction formulas and explain why the Radon formula cannot directly work
      with truncated projection data. Also, we introduce a gamma coordinate system,
      analyze its properties, compute the Jacobian of the coordinate transform, and
      define weight functions for the inverse Fourier transform assuming a simple
      scanning model. Then, we generate Orlov's theorem and a weighted Radon formula
      from the inverse Fourier transform in the new system. Furthermore, we present the
      motion equation of the frequency plane and the conditions for sharp points of the
      instantaneous rotation axis. Our analysis on the motion of the frequency plane is
      related to the Frenet-Serret theorem in the differential geometry.

PMID- 21076521
TI  - Synthesis, Crystal Structures, and DNA Binding Properties of Zinc(II) Complexes
      with 3-Pyridine Aldoxime.
AB  - The employment of 3-pyridine aldoxime, (3-py)CHNOH, in Zn(II) chemistry has
      afforded two novel compounds: [Zn(acac)(2){(3-py)CHNOH}].H(2)O (1.H(2)O) [where
      acac(-) is the pentane-2,4-dionato(-1) ion] and [Zn(2)(O(2)CMe)(4){(3
      py)CHNOH}(2)] (2). Complex 1.H(2)O crystallizes in the monoclinic space group
      P2(1)/n. The Zn(II) ion is five-coordinated, surrounded by four oxygen atoms of
      two acac(-) moieties and by the pyridyl nitrogen atom of the (3-py)CHNOH ligand.
      Molecules of 1 interact with the water lattice molecules forming a 2D hydrogen
      bonding network. Complex 2 crystallizes in the triclinic P-1 space group and
      displays a dinuclear paddle-wheel structure. Each Zn(II) exhibits a perfect
      square pyramidal geometry, with four carboxylate oxygen atoms at the basal plane
      and the pyridyl nitrogen of one monodentate (3-py)CHNOH ligand at the apex. DNA
      mobility shift assays were performed for the determination of the in vitro effect
      of both complexes on the integrity and the electrophoretic mobility of pDNA.

PMID- 21076522
TI  - Harnessing the effect of adoptively transferred tumor-reactive T cells on
      endogenous (host-derived) antitumor immunity.
AB  - Adoptive T cell transfer therapy, the ex vivo activation, expansion, and
      subsequent administration of tumor-reactive T cells, is already the most
      effective therapy against certain types of cancer. However, recent evidence in
      animal models and clinical trials suggests that host conditioning interventions
      tailored for some of the most aggressive and frequent epithelial cancers will be
      needed to maximize the benefit of this approach. Similarly, the subsets, stage of
      differentiation, and ex vivo expansion procedure of tumor-reactive T cells to be
      adoptively transferred influence their in vivo effectiveness and may need to be
      adapted for different types of cancer and host conditioning interventions. The
      effects of adoptively transferred tumor-reactive T cells on the mechanisms of
      endogenous (host-derived) antitumor immunity, and how to maximize their combined
      effects, are further discussed.

PMID- 21076524
TI  - Synthesis and Crystal Structure Characterization of Zinc (II) Tetronic Acid
      Complexes.
AB  - The synthesis and characterization of two new tetronic acid zinc (II) complexes
      of the empirical formulae [Zn(L-H)(2)(H(2)O)(2)] (1) and [Zn(L
      H)(2)(H(2)O)(MeOH)]H(2)O (2) found within the same crystal are reported. The zinc
      ions bind through alkoxide and carbonyl groups of the ligand 3-methoxycarbonyl-5
      phenyl tetronic acid (LH) as indicated by (1)H NMR and X-ray crystallographic
      studies. These complexes promote intra- and intermolecular interactions, such as
      hydrogen bonding and pi stacking, giving place to the formation of molecular
      aggregates.

PMID- 21076523
TI  - Dendritic cell-based immunotherapy for prostate cancer.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells (APCs), which
      display an extraordinary capacity to induce, sustain, and regulate T-cell
      responses providing the opportunity of DC-based cancer vaccination strategies.
      Thus, clinical trials enrolling prostate cancer patients were conducted, which
      were based on the administration of DCs loaded with tumor-associated antigens.
      These clinical trials revealed that DC-based immunotherapeutic strategies
      represent safe and feasible concepts for the induction of immunological and
      clinical responses in prostate cancer patients. In this context, the
      administration of the vaccine sipuleucel-T consisting of autologous peripheral
      blood mononuclear cells including APCs, which were pre-exposed in vitro to the
      fusion protein PA2024, resulted in a prolonged overall survival among patients
      with metastatic castration-resistant prostate cancer. In April 2010, sipuleucel-T
      was approved by the United States Food and Drug Administration for prostate
      cancer therapy.

PMID- 21076525
TI  - Betel nut chewing and subclinical ischemic heart disease in diabetic patients.
AB  - Background. This study investigated the association between betel nut chewing and
      subclinical ischemic heart disease (IHD) in Taiwanese type 2 diabetic patients.
      Methods. A total of 394 male patients aging >=45 years and without previous heart
      disease were studied. Among them 349 had no habit of chewing betel nut and 45
      possessed the habit for >=5 years. Subclinical IHD was diagnosed by a Minnesota
      coded resting electrocardiogram and was present in 71 cases. Statistical analyses
      were performed considering confounding effects of age, diabetic duration,
      smoking, body mass index, blood pressure, dyslipidemia, and metabolic control
      status. Results. Betel nut chewers were younger and had higher prevalence of
      smoking (86.7% versus 60.5%), higher body mass index, poorer glycemic control,
      and higher prevalence of subclinical IHD (28.9% versus 16.6%). Patients with
      subclinical IHD were older and had higher prevalence of betel nut chewing (18.0%
      versus 9.9%). The multivariate-adjusted odds ratio for subclinical IHD for
      chewers versus nonchewers was 4.640 (1.958-10.999). The adjusted odds ratios in
      younger or older patients divided by the median age of 63 years were similar:
      4.724 (1.346-16.581) and 4.666 (1.278-17.028), respectively. Conclusions. Betel
      nut chewing is significantly associated with increased risk of subclinical IHD.

PMID- 21076526
TI  - Prostaglandin-induced cystoid macular edema following routine cataract
      extraction.
AB  - To our knowledge, we are reporting the first case of a 59-year-old man who
      developed recurrent CME with three separate trials of three different
      prostaglandin class drugs following uncomplicated phacoemulsification with
      intraocular lens implantation. Despite multiple reports of individual
      prostaglandin (PG) analogues being suggested as the cause of CME, there are no
      recommendations regarding withholding these medications in the perioperative
      period. Our patient first developed CME OD 4-months post uncomplicated cataract
      extraction. XALATAN (Latanoprost) had been restarted after surgery and
      discontinued at onset of CME. While off XALATAN (Latanoprost), the patient's CME
      resolved, but his IOP rose. The patient was started on LUMIGAN (Bimatoprost) to
      control the IOP, but within weeks his CME recurred. The patient's CME was again
      treated and his IOP remained acceptable, but then progressively increased.
      TRAVATAN (Travoprost) was attempted, but he presented with a third round of CME.
      Definitive conclusions about causal relationships cannot be made without well
      designed, prospective clinical trials addressing this issue.

PMID- 21076527
TI  - Neuroprotection by the Traditional Chinese Medicine, Tao-Hong-Si-Wu-Tang, against
      Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia in Rats.
AB  - Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese medicine (TMC). In
      the present study, oral administration of THSWT (0.7 and 1.4 g kg(-1)day(-1)) for
      14 days before MCAO dose-dependently attenuated focal cerebral ischemia in rats.
      MCAO-induced focal cerebral ischemia was associated with increases in hypoxia
      inducible factor (HIF)-1alpha, inducible nitric oxide synthase (iNOS), tumor
      necrosis factor (TNF)-alpha, and active caspase-3 expressions in ischemic
      regions. These expressions were obviously inhibited by 0.7 g kg(-1)day(-1) THSWT
      treatment. In addition, THSWT inhibited platelet aggregation stimulated by
      collagen in washed platelets. In an in vivo study, THSWT (16 g kg(-1))
      significantly prolonged platelet plug formation in mice. However, THSWT (20 and
      40 MUg mL(-1)) did not significantly reduce the electron spin resonance (ESR)
      signal intensity of hydroxyl radical (OH(*)) formation. In conclusion, the most
      important findings of this study demonstrate for the first time that THSWT
      possesses potent neuroprotective activity against MCAO-induced focal cerebral
      ischemia in vivo. This effect may be mediated, at least in part, by the
      inhibition of both HIF-1alpha and TNF-alpha activation, followed by the
      inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation
      (active caspase-3), and platelet activation, resulting in a reduction in the
      infarct volume in ischemia-reperfusion brain injury.

PMID- 21076529
TI  - Acute Hepatitis B and Acute HIV Coinfection in an Adult Patient: A Rare Case
      Report.
AB  - Acute HIV and acute hepatitis B coinfection is extremely rare. A 23-year-old
      homosexual man was admitted to our hospital with 5-day history of fever, malaise,
      and back pain with initial laboratory values showing severe transaminitis. The
      clinical picture was initially suggestive of acute viral hepatitis, which on
      further testing revealed acute hepatitis B and acute HIV coinfection. Although
      the patient was asymptomatic, a decision was made to start antiretroviral
      therapy. At 2-month followup, liver function tests were normal with undetectable
      viral loads. The early treatment of acute HIV/HBV coinfections likely contributed
      to eventual seroconversion with immunity to HBV in a severely immunocompromised
      host. To the best of our knowledge, this is the first case report of acute
      Hepatitis B and acute HIV coinfection and its management. In conclusion, early
      treatment of acute hepatitis B in immunocompromised patients may be beneficial.

PMID- 21076528
TI  - The role of HDAC6 in cancer.
AB  - Histone deacetylase 6 (HDAC6), a member of the HDAC family whose major substrate
      is alpha-tubulin, has become a target for drug development to treat cancer due to
      its major contribution in oncogenic cell transformation. Overexpression of HDAC6
      correlates with tumorigenesis and improved survival; therefore, HDAC6 may be used
      as a marker for prognosis. Previous work demonstrated that in multiple myeloma
      cells, inhibition of HDAC6 results in apoptosis. Furthermore, HDAC6 is required
      for the activation of heat-shock factor 1 (HSF1), an activator of heat-shock
      protein encoding genes (HSPs) and CYLD, a cylindromatosis tumor suppressor gene.
      HDAC6 contributes to cancer metastasis since its upregulation increases cell
      motility in breast cancer MCF-7 cells and its interaction with cortactin
      regulates motility. HDAC6 also affects transcription and translation by
      regulating the heat-shock protein 90 (Hsp90) and stress granules (SGs),
      respectively. This review will discuss the role of HDAC6 in the pathogenesis and
      treatment of cancer.

PMID- 21076530
TI  - High-sensitivity C-reactive protein: an independent risk factor for left
      ventricular hypertrophy in patients with lupus nephritis.
AB  - OBJECTIVE: To determine the prevalence of left ventricular hypertrophy (LVH) and
      its associated risk factors in lupus nephritis (LN) patients. METHODS: 287 LN
      patients (age: 38.54 +/- 13.31, 262 female) were recruited. Echocardiography and
      serum high-sensitivity C-reactive protein (hs-CRP) were measured. Their
      relationship was evaluated by univariate correlation analysis and multivariate
      regression analysis. RESULTS: The prevalence of LVH in this cohort was 21.25% (n
      = 61). Serum hs-CRP level was significantly elevated in patients with LVH
      compared to those without (8.03 (3.22-30.95) versus 3.93 (1.48-9.48) mg/L, P <
      .01), and correlated with left ventricular mass index (LVMI) (r = 0.314, P =
      .001). Multivariate regression analysis further confirmed that hs-CRP was an
      independent risk factor (beta = 0.338, P = .002) for LVH in patients with LN.
      CONCLUSIONS: Our findings demonstrated that serum hs-CRP level is independently
      correlated with LVMI and suggested that measurement of hs-CRP may provide
      important clinical information to investigate LVH in LN patients.

PMID- 21076531
TI  - Thymoglobulin induction dosing strategies in a low-risk kidney transplant
      population: three or four days?
AB  - The optimal dose and duration of rabbit antithymocyte globulin (rATG) induction
      has not been defined. Methods. We compared the safety and efficacy of 2 dosing
      strategies, rATG 1.5 mg/kg for 4 days (n = 59) versus 2 mg/kg for 3 days (n =
      59), in a retrospective, cohort study. Results. Two-year rejection-free survival
      was 95% in each group (P = .983). Renal function and infection rates were
      similar. The incidence of leucopenia was similar, although the 2 mg/kg group was
      more likely to be thrombocytopenic on day 2 (4% versus 28%, P = .04). Length of
      stay tended to be longer for the 1.5 mg/kg group (6.0 +/- 3.7 versus 5.1 +/- 1.9
      days P = .104). A cost savings of $920 per patient for rATG were seen in the 2
      mg/kg group (P = .122). Conclusions. Shorter, more intense dosing of rATG is safe
      and effective. The 3-day dose strategy resulted in a clinically shorter length of
      stay and may result in cost savings.

PMID- 21076532
TI  - Regulation of posttranscriptional modification as a possible therapeutic approach
      for retinal neuroprotection.
AB  - Understanding pathogenesis at the molecular level is the first step toward
      developing new therapeutic approaches. Here, we review the molecular mechanisms
      of visual dysfunction in two common diseases, innate chorioretinal inflammation
      and diabetic retinopathy, and the role of the ubiquitin-proteasome system (UPS)
      in both processes. In innate chorioretinal inflammation, interleukin-6 family
      ligands induce STAT3 activation in photoreceptors, which causes UPS-mediated
      excessive degradation of the visual substance, rhodopsin. In diabetic
      retinopathy, angiotensin II type 1 receptor (AT1R) signaling activates ERK in the
      inner layers of the retina, causing UPS-mediated excessive degradation of the
      synaptic vesicle protein, synaptophysin. This latter effect may decrease synaptic
      activity, in turn adversely affecting neuronal survival. Both mechanisms involve
      increased UPS activity and the subsequent excessive degradation of a protein
      required for visual function. Finally, we review the therapeutic potential of
      regulating the UPS to protect tissue function, citing examples from clinical
      applications in other medical fields.

PMID- 21076533
TI  - Phases I-III Clinical Trials Using Adult Stem Cells.
AB  - First randomized clinical trials have demonstrated that stem cell therapy can
      improve cardiac recovery after the acute phase of myocardial ischemia and in
      patients with chronic ischemic heart disease. Nevertheless, some trials have
      shown that conflicting results and uncertainties remain in the case of mechanisms
      of action and possible ways to improve clinical impact of stem cells in cardiac
      repair. In this paper we will examine the evidence available, analyze the main
      phase I and II randomized clinical trials and their limitations, discuss the key
      points in the design of future trials, and depict new directions of research in
      this fascinating field.

PMID- 21076534
TI  - Torsion of Testis in an Infant with Unilateral UDT.
AB  - Torsion of an undescended testis is uncommon. Torsion of a cryptorchid testicle
      presents a nonspecific symptomatology. Clinical suspicion indicates emergent
      surgical exploration, irrespective of Doppler ultrasound with its inherent false
      negative results. Management of the contralateral testis is controversial. We
      emphasize the need of a complete physical examination of the child who goes to
      the emergency room with nonspecific symptoms of abdominal pain and ipsilateral
      empty hemiscrotum to rule out torsion of a cryptorchid testicle. Herein, we
      report a one-year-old infant with missed torsion of undescended left testis.

PMID- 21076535
TI  - Use of ultra high performance liquid chromatography-tandem mass spectrometry to
      demonstrate decreased serum statin levels after extracorporeal LDL-cholesterol
      elimination.
AB  - BACKGROUND: Using our statin analysis method, it was possible to uncover a
      significant drop in statin levels (atorvastatin, simvastatin, and metabolites)
      after extracorporeal LDL-cholesterol elimination (EE) in severe familial
      hypercholesterolemia (FH). The purpose of this work was to identify the mechanism
      underlying this drop and its clinical significance as well as to propose measures
      to optimize a pharmacotherapeutical regimen that can prevent the loss of statins.
      METHODS: Ultra High Performance Liquid Chromatography (UHPLC) connected to the
      triple quadrupole MS/MS system was used. Patients. A group of long-term treated
      patients (3-12 years of treatment) with severe FH (12 patients) and treated
      regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade
      filtration) were included in this study. RESULTS: After EE, the level of statins
      and their metabolites decreased (atorvastatin before/after LDL-apheresis:
      8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific
      loss was found (concentration of atorvastatin for LDL
      apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in
      filters). To prevent substantial loss of statin concentrations, a
      pharmacotherapeutic regimen with a longer time interval between the dose of
      statins and EE is recommended (15 hours). CONCLUSIONS: A specific loss of statins
      was found in adsorbent columns and filters. The decrease can be prevented by the
      suggested dosage scheme.

PMID- 21076536
TI  - Penile fracture with associated urethral rupture.
AB  - Penile fracture of the erect penis is an uncommon but emergent urological trauma.
      Potential outcomes include erectile dysfunction, penile curvature, and urethral
      injury. Treatment is emergent surgical repair. We present the case of a 42-year
      old man with a penile fracture complicated by a urethral rupture and subsequent
      repair. A discussion of the key aspects of this condition is presented.

PMID- 21076537
TI  - Hemophagocytic Syndrome Associated with Hodgkin's Lymphoma First Presenting as
      Fever and Pancytopenia.
AB  - Background. Hemophagocytic syndrome (HPS) is characterized by a hyperinflammatory
      reaction followed by alteration in cytotoxic function of Th1 lymphocytes and
      natural killer cells. We report a rare case of a patient that presented with
      fever and pancytopenia due to HPS associated with Hodgkin's lymphoma (HL). Case
      Report. A 69-year-old Caucasian woman was admitted presenting with complaints of
      fever, seizures, and low back pain that had lasted for two weeks. Laboratorial
      data showed pancytopenia. Bone marrow biopsy revealed infiltration by Reed
      Sternberg cells and hemophagocytosis signs. Imaging studies showed mediastinal
      lymph nodes (stage IV B). She had been treated with ABVD (doxorubicin, bleomycin,
      vinblastine, and dacarbazine) followed by a good response. Conclusion. HPS
      associated with HL is a very rare and lethal disease, with mortality rates of
      about 15% to 60%. The prompt diagnosis of the underlying lymphoma may be an
      important strategy for optimizing the clinical approach and outcome.

PMID- 21076538
TI  - Anti-VEGF therapy in breast and lung mouse models of cancers.
AB  - Cancer is the second leading cause of death in the world after cardiovascular
      diseases. Some types of cancer cells often travel to other parts of the body
      through blood circulation or lymph vessels, where they begin to grow. This
      process is recognized as metastasis. Angiogenesis is the formation of new blood
      vessels from existing vessel. Normally angiogenesis is a healthy process, that
      helps the body to heal wounds and repair damaged body tissues, whereas in
      cancerous condition this process supports new blood vessels formation that
      provide a tumor with its own blood supply, nutrients and allow it to grow. The
      most important proximal factor for angiogenesis is the vascular endothelial
      growth factor VEGF. Angioinhibition is a form of targeted therapy that uses drugs
      to stop tumors from making new blood vessels. Therefore, in this paper we analyse
      the importance of VEGF as target of cancer therapy, analysing murine models.

PMID- 21076539
TI  - The fat-fed apolipoprotein E knockout mouse brachiocephalic artery in the study
      of atherosclerotic plaque rupture.
AB  - Atherosclerosis has been studied in animals for almost a century, yet the events
      leading up to the rupture of an atherosclerotic plaque (the underlying cause of
      the majority of fatal thrombosis formation) have only been studied in the past
      decade, due in part to the development of a mouse model of spontaneous plaque
      rupture. Apolipoprotein E knockout mice, when fed a high-fat diet, consistently
      develop lesions in the brachiocephalic artery that rupture at a known time point.
      It is therefore now possible to observe the development of lesions to elucidate
      the mechanisms behind the rupture of plaques. Critics argue that the model does
      not replicate the appearance of human atherosclerotic plaque ruptures. The
      purpose of this review is to highlight the reasons why we should be looking to
      the apolipoprotein E knockout mouse to further our understanding of plaque
      rupture.

PMID- 21076540
TI  - Characterization of activity of a potential food-grade leucine aminopeptidase
      from kiwifruit.
AB  - Aminopeptidase (AP) activity in ripe but firm fruit of Actinidia deliciosa was
      characterized using L-leucine-p-nitroanilide as a substrate. The enzyme activity
      was the highest under alkaline conditions and was thermolabile. EDTA, 1,10
      phenanthroline, iodoacetamide, and Zn(2+) had inhibitory effect while a low
      concentration of dithiothreitol (DTT) had stimulatory effect on kiwifruit AP
      activity. However, DTT was not essential for the enzyme activity. The results
      obtained indicated that the kiwifruit AP was a thiol-dependent metalloprotease.
      Its activity was the highest in the seeds, followed by the core and pericarp
      tissues of the fruit. The elution profile of the AP activity from a DEAE
      cellulose column suggested that there were at least two AP isozymes in kiwifruit:
      one unadsorbed and one adsorbed fractions. It is concluded that useful food-grade
      aminopeptidases from kiwifruit could be revealed using more specific substrates.

PMID- 21076541
TI  - C-reactive protein and gamma-glutamyltransferase concentrations in relation to
      the prevalence of type 2 diabetes diagnosed by glucose or HbA1c criteria in
      Chinese adults in Qingdao, China.
AB  - AIMS: To investigate the association of C-reactive protein (CRP) and gamma
      glutamyltransferase (GGT) concentrations with newly diagnosed diabetes defined by
      either glucose or HbA1c criteria in Chinese adults. METHODS: A population-based
      cross-sectional study was conducted in 2006. Data from 1167 men and 1607 women
      aged 35-74 years were analyzed. Diabetes was defined according to either glucose
      or HbA1c criteria alone. RESULTS: Compared with nondiabetes, multivariate
      adjusted OR (95%CI) was 1.13 (0.90,1.42) in men and 1.21 (1.00,1.45) in women for
      CRP and 1.42 (1.18,1.72) and 1.57 (1.31,1.87) for GGT, respectively. Neither CRP
      nor GGT was associated with the presence of diabetes defined by the HbA1c
      criterion. CONCLUSIONS: The effect of elevated CRP on diabetes defined by the
      glucose criterion was mediated through obesity, but elevated GGT was an
      independent risk factor for diabetes in this Chinese population. None of the two
      was, however, associated with the elevated HbA1c concentrations.

PMID- 21076542
TI  - Biphasic Effect of Phyllanthus emblica L. Extract on NSAID-Induced Ulcer: An
      Antioxidative Trail Weaved with Immunomodulatory Effect.
AB  - Amla (Phyllanthus emblica L.), apart from its food value, can be used as a
      gastroprotective agent in non steroidal anti-inflammatory drug (NSAID)-induced
      gastropathy. It has been suggested that the antioxidative property of amla is the
      key to its therapeutic effect. Hence, on the basis of in vitro antioxidative
      potential, the ethanolic extract of amla (eAE) was selected for in vivo study in
      NSAID-induced ulcer. Intriguingly, eAE showed biphasic activity in ulcerated
      mice, with healing effect observed at 60 mg/kg and an adverse effect at 120
      mg/kg.The dose-dependent study revealed that switching from anti-oxidant to pro
      oxidant shift and immunomodulatory property could be the major cause for its
      biphasic effect, as evident from the total antioxidant status, thiol
      concentration, lipid peroxidation, protein carbonyl content followed by mucin
      content, PGE(2) synthesis and cytokine status. Further, Buthionine sulfoxamine
      (BSO) pretreatment established the potential impact of antioxidative property in
      the healing action of eAE. However, eAE efficiently reduced pro-inflammatory
      cytokine (TNF-alpha and IL-1beta) levels and appreciably upregulate anti
      inflammatory cytokine (IL-10) concentration. In conclusion, gastric ulcer healing
      induced by eAE was driven in a dose-specific manner through the harmonization of
      the antioxidative property and modulation of anti-inflammatory cytokine level.

PMID- 21076543
TI  - Should CSF Biomarkers Support a Routine Analysis for Early Diagnosis of
      Alzheimer's Disease?

PMID- 21076544
TI  - Role of PPARalpha and Its Agonist in Renal Diseases.
AB  - Peroxisome proliferator-activated receptor (PPAR)-alpha, a member of a large
      nuclear receptor superfamily, plays a major role in the regulation of lipid
      metabolism. Recently, PPARalpha activation has been shown to confer additional
      benefits on endothelial function, kidney function, and anti-inflammation,
      suggesting that PPARalpha agonists may be good candidates for treating acute
      renal failure. In clinical application, PPAR-alpha activators, such as
      hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects
      on metabolic syndrome and cardiovascular disease. This paper focuses on signaling
      pathways, ligand selectivity, and physio-pathological roles of PPARalpha in
      kidney diseases and the therapeutic utility of PPARalpha modulators in the
      treatment of diabetes and inflammation-induced nephropathy. Implication of new
      and more potent PPAR-alpha activators could provide important insights into the
      overall benefits of activating PPAR-alpha clinically for the treatment of
      dyslipidemia and the prevention of diabetic or inflammation-induced nephropathy
      in the future.

PMID- 21076545
TI  - Cancer stem cells in head and neck squamous cell carcinoma.
AB  - Accumulating evidence suggests that self-renewal and differentiation capabilities
      reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs),
      whereas the remaining tumor cell population lacks the ability to initiate tumor
      development or support continued tumor growth. In head and neck squamous cell
      carcinoma (HNSCC), as with other malignancies, cancer stem cells have been
      increasingly shown to have an integral role in tumor initiation, disease
      progression, metastasis and treatment resistance. In this paper we summarize the
      current knowledge of the role of CSCs in HNSCC and discuss the therapeutic
      implications and future directions of this field.

PMID- 21076546
TI  - The effect of different foam concentrations on sperm motility in Japanese quail.
AB  - A study was conducted to determine the effect of foam extract on sperm motility
      in the male Japanese quail (Coturnix coturnix japonica). Adult male quails (<12
      weeks) of heavy body weight strain were housed in individual cages and divided
      into 5 groups according to the size of their cloacal glands. The data indicated
      that the size of the cloacal gland was positively correlated with the frequency
      of foam secretion and total foam production. One gram of freshly collected clean
      foam was mixed with 1.0 mL of normal saline and homogenized for 10 minutes. After
      centrifugation at 35 000 rpm, the supernatant was used as 100% foam extract. The
      extract was diluted to 1:40, 1:20, 1:10, and 1:4 with normal saline to produce
      2.5, 5.0, 10, and 25% foam extracts, respectively. 5% foam extract enhanced sperm
      survival at room temperature (30 degrees -35 degrees C) for 2 to 3 hrs, whereas
      higher concentrations (10% and above) suppressed sperm motility. From this study,
      it may be concluded that foam secretion and quantity of foam are directly
      proportional to the size of the cloacal gland and that the foam enhances and
      prolongs sperm motility, in vitro at an optimum concentration of 5%.

PMID- 21076547
TI  - Treatments to Optimize the Use of Artificial Insemination and Reproductive
      Efficiency in Beef Cattle under Tropical Environments.
AB  - Bos indicus cattle, the preferred genetic group in tropical climates, are
      characterized by having a lower reproductive efficiency than Bos taurus. The
      reasons for the poorer reproductive efficiency of the Bos indicus cows include
      longer lengths of gestation and postpartum anestrus, a short length of estrous
      behavior with a high incidence of estrus occurring during the dark hours, and
      puberty at older age and at a higher percentage of body weight relative to mature
      body weight. Moreover, geography, environment, economics, and social traditions
      are factors contributing for a lower use of reproductive biotechnologies in
      tropical environments. Hormonal protocols have been developed to resolve some of
      the reproductive challenges of the Bos indicus cattle and allow artificial
      insemination, which is the main strategy to hasten genetic improvement in
      commercial beef ranches. Most of these treatments use exogenous sources of
      progesterone associated with strategies to improve the final maturation of the
      dominant follicle, such as temporary weaning and exogenous gonadotropins. These
      treatments have caused large impacts on reproductive performance of beef cattle
      reared under tropical areas.

PMID- 21076548
TI  - Perspectives on Regulatory T Cell Therapies.
AB  - Adoptive transfer in animal models clearly indicate an essential role of CD4+
      CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of
      autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and
      development of drugs that specifically enhance T(reg) cell function and
      development represent promising tools to establish dominant tolerance. So far,
      lack of specific markers to differentiate human T(reg) cells from activated CD4+
      CD25+ effector T cells, which also express FOXP3 at different levels, hampered
      such an approach. Recent identification of the orphan receptor glycoprotein-A
      repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule
      that dominantly controls FOXP3 via a positive feedback loop opens up new
      perspectives for molecular and cellular therapies. This brief review focuses on
      the role of GARP as a safeguard of a complex regulatory network of human T(reg)
      cells and its implications for regulatory T cell therapies in autoimmunity and
      graft-versus-host disease.

PMID- 21076549
TI  - Evaluation of Different Preparation Procedures of Pathogen Reduction
      Technology(Mirasol(r))-Treated Platelets Collected by Plateletpheresis.
AB  - SUMMARY: BACKGROUND: The Mirasol(r) pathogen reduction technology (PRT) for
      platelet concentrates (PC) uses riboflavin and UV light (270-360 nm). We
      evaluated the impact of PRT on platelets in comparison to standard single-donor
      PC. MATERIAL AND METHODS: Platelets were resuspended in autologous plasma. After
      2 h rest without agitation, PC were split into an untreated control unit (C-PC)
      and an immediately treated unit (T-PC) (series I). In series IV, split PC were
      stored under agitation over night before PRT was carried out. Platelet quality
      was assessed by pH, glucose consumption, lactate production rate, LDH, soluble
      sCD62p and CD62p expression with and without TRAP (thrombin receptor-activating
      peptide) over 7 days. RESULTS: SERIES I: On day 5, pH values were lower for T-PC
      (6.8 +/- 0.2 vs. 7.4 +/- 0.1, C-PC), accompanied by a higher glucose consumption
      rate of 0.069 +/- 0.016 vs. 0.035 +/- 0.006 mmol/10(12) platelets/h and lactate
      production rate of 0.126 +/- 0.031 vs. 0.063 +/- 0.011 mmol/10(12) platelets/h.
      CD62p using TRAP was lower for T-PC (50 +/- 11 vs. 62 +/- 14%). Baseline
      activation was higher in T-PC (35 +/- 12 vs. 28 +/- 15%). Longer initial rest
      time had no impact on these results (series II/III/IV). CONCLUSION: PRT leads to
      an increase of platelet metabolism and activation independent of the length of
      the initial rest times. PC resuspended in autologous plasma should be stored at
      maximum up to day 5.

PMID- 21076550
TI  - Evaluation of Quality Parameters for Cord Blood Donations.
AB  - SUMMARY: BACKGROUND: Umbilical cord blood (CB) is widely used for hematopoietic
      stem cell transplantation and holds promise for the development of innovative
      medicinal products. In order to find out whether the conditions for collection
      and storage before processing might have an impact on the quality of CB
      preparations, viability and the clonogenic potential were assessed. METHODS: CB
      was collected under field conditions. Flow cytometry was used to determine
      leukocytes, CD34/CD45+ cells, viability, and nucleated red blood cells (NRBC).
      Clonogenic activity was determined using isolated mononuclear cells (MNC).
      RESULTS: Neither plasma citrate concentrations nor storage temperature (within 24
      h) affected cell viability or colony formation. After storage for 49-80 h,
      leukocyte viability declined by about 16% compared to CB stored up to 24 h. In
      contrast, the clonogenic activity and CD34/CD45+ cell content were not affected.
      A higher gestational age was associated with a lower yield of clonogenic activity
      compared to midterm deliveries. NRBC varied widely (median 7.3%; range 0.63
      17.3%) without relation to gestational age or colony formation. There was a close
      correlation between the percentage of viable CD34/CD45+ cells and colony
      formation (r = 0.77 for CFU-GM; r = 0.75 for CFU-C). CONCLUSIONS: The content of
      viable CD34/CD45+ cells represents the clonogenic activity of CB preparations.
      Therefore, determination of viable CD34/CD45+ cells should be generally performed
      as a routine quality control assay.

PMID- 21076551
TI  - Turning CD34 Non-Mobilizers into Mobilizers: A Case Report Involving Plerixafor
      (AMD3100).
AB  - SUMMARY: OBJECTIVE: In a significant proportion of patients with hematologic
      malignancies (5-30%) poor mobilization of hematopoietic stem cells (HSC) is
      observed. This compromises the application of effective and potentially curative
      high-dose chemotherapy (HDC) treatment. CASE REPORT: Here we report the case of a
      38-year-old female patient who was treated for recurrent follicular B-cell non
      Hodgkin's lymphoma grade III. In this patient, we failed twice to mobilize stem
      cells using chemotherapy followed by granulocyte-colony stimulating factor (G
      CSF). Recently a new chemokine receptor CXCR4 antagonist, AMD3100 (plerixafor),
      was introduced which can be combined with G-CSF mobilization and has been
      reported to increase the number of harvested stem cells significantly. Using this
      protocol, we were able to harvest a HSC product. This product was transplanted 3
      weeks after the harvest (after HDC), and the patient had an uncomplicated
      recovery of granulopoiesis (day 11 after transplantation of autologous HSC).
      CONCLUSION: Plerixafor has the potency to become an important tool in mobilizing
      HSC, especially in those patients in whom HSC cannot be mobilized by the
      combination of G-CSF and chemotherapy alone.

PMID- 21076552
TI  - Blood Donation, Payment, and Non-Cash Incentives: Classical Questions Drawing
      Renewed Interest.
AB  - Blood is scarce, and ensuring a sufficient blood supply remains difficult for
      many countries. Payment for blood as a strategy to increase donations has
      remained highly controversial for decades, and the debate about ethical issues in
      paying donors has become somewhat stuck. At least from a policy perspective, it
      is important to find a compromise which allows for devising and implementing
      acceptable and successful policies to increase the blood supply. In this paper,
      such a compromise is developed both from a theoretical and empirical perspective,
      namely implementing well-designed non-cash incentives which cut across the rigid
      dichotomy of altruistic donations versus payment for donations. In order for this
      compromise to work, more attention to donation motives, the choice architecture,
      and the setting in blood donation needs to be paid.

PMID- 21076554
TI  - Women's and children's health: from pledges to action.

PMID- 21076555
TI  - The impact of cell phones on public health surveillance.

PMID- 21076556
TI  - Access to essential medicines in national constitutions.

PMID- 21076557
TI  - At last a global response to viral hepatitis.
AB  - A million people die from viral hepatitis every year, yet until now the public
      health response has been patchy and piecemeal, overwhelmed by the sheer scale of
      the problem. Jane Parry reports.

PMID- 21076558
TI  - Bridging the gap in South Africa.
AB  - The South African government's proposed national insurance scheme aims to tackle
      the stark divide in health care between rich and poor. Claire Keeton reports.

PMID- 21076559
TI  - Antimicrobial resistance: revisiting the "tragedy of the commons".
AB  - When the NDM1 enzyme-containing "superbugs" struck in India, Pakistan and the
      United Kingdom earlier this year, media reports blamed medical tourism for its
      spread. But in this interview, Professor John Conly argues that the overuse and
      misuse of antibiotics leading to antimicrobial resistance - the theme of World
      Health Day 2011 - is the more important topic.

PMID- 21076561
TI  - Intermittent preventive treatment for malaria in infants: a decision-support tool
      for sub-Saharan Africa.
AB  - OBJECTIVE: To develop a decision-support tool to help policy-makers in sub
      Saharan Africa assess whether intermittent preventive treatment in infants (IPTi)
      would be effective for local malaria control. METHODS: An algorithm for
      predicting the effect of IPTi was developed using two approaches. First, study
      data on the age patterns of clinical cases of Plasmodium falciparum malaria,
      hospital admissions for infection with malaria parasites and malaria-associated
      death for different levels of malaria transmission intensity and seasonality were
      used to estimate the percentage of cases of these outcomes that would occur in
      children aged <10 years targeted by IPTi. Second, a previously developed
      stochastic mathematical model of IPTi was used to predict the number of cases
      likely to be averted by implementing IPTi under different epidemiological
      conditions. The decision-support tool uses the data from these two approaches
      that are most relevant to the context specified by the user. FINDINGS: Findings
      from the two approaches indicated that the percentage of cases targeted by IPTi
      increases with the severity of the malaria outcome and with transmission
      intensity. The decision-support tool, available on the Internet, provides
      estimates of the percentage of malaria-associated deaths, hospitalizations and
      clinical cases that will be targeted by IPTi in a specified context and of the
      number of these outcomes that could be averted. CONCLUSION: The effectiveness of
      IPTi varies with malaria transmission intensity and seasonality. Deciding where
      to implement IPTi must take into account the local epidemiology of malaria. The
      Internet-based decision-support tool described here predicts the likely
      effectiveness of IPTi under a wide range of epidemiological conditions.

PMID- 21076562
TI  - Developing the World Health Organization Disability Assessment Schedule 2.0.
AB  - OBJECTIVE: To describe the development of the World Health Organization
      Disability Assessment Schedule 2.0 (WHODAS 2.0) for measuring functioning and
      disability in accordance with the International Classification of Functioning,
      Disability and Health. WHODAS 2.0 is a standard metric for ensuring scientific
      comparability across different populations. METHODS: A series of studies was
      carried out globally. Over 65,000 respondents drawn from the general population
      and from specific patient populations were interviewed by trained interviewers
      who applied the WHODAS 2.0 (with 36 items in its full version and 12 items in a
      shortened version). FINDINGS: The WHODAS 2.0 was found to have high internal
      consistency (Cronbach's alpha, alpha: 0.86), a stable factor structure; high test
      retest reliability (intraclass correlation coefficient: 0.98); good concurrent
      validity in patient classification when compared with other recognized disability
      measurement instruments; conformity to Rasch scaling properties across
      populations, and good responsiveness (i.e. sensitivity to change). Effect sizes
      ranged from 0.44 to 1.38 for different health interventions targeting various
      health conditions. CONCLUSION: The WHODAS 2.0 meets the need for a robust
      instrument that can be easily administered to measure the impact of health
      conditions, monitor the effectiveness of interventions and estimate the burden of
      both mental and physical disorders across different populations.

PMID- 21076563
TI  - The impact of an emergency hiring plan on the shortage and distribution of nurses
      in Kenya: the importance of information systems.
AB  - OBJECTIVE: To analyse the effect of Kenya's Emergency Hiring Plan for nurses on
      their inequitable distribution in rural and underserved areas. METHODS: We used
      data from the Kenya Health Workforce Informatics System on the nursing workforce
      to determine the effect of the Emergency Hiring Plan on nurse shortages and
      maldistribution. The total number of nurses, the number of nurses per 100,000
      population and the opening of previously closed or new heath facilities were
      recorded. FINDINGS: Of the 18,181 nurses employed in Kenya's public sector in
      2009, 1836 (10%) had been recruited since 2005 through the Emergency Hiring Plan.
      Nursing staff increased by 7% in hospitals, 13% in health centres and 15% in
      dispensaries. North Eastern province, which includes some of the most remote
      areas, benefited most: the number of nurses per 100,000 population increased by
      37%. The next greatest increase was in Nyanza province, which has the highest
      prevalence of HIV infection in Kenya. Emergency Hiring Plan nurses enabled the
      number of functioning public health facilities to increase by 29%. By February
      2010, 94% of the nurses hired under pre-recruitment absorption agreements had
      entered the civil service. CONCLUSION: The Emergency Hiring Plan for nurses
      significantly increased health services in Kenya's rural and underserved areas
      over the short term. Preliminary indicators of sustainability are promising, as
      most nurses hired are now civil servants. However, continued monitoring will be
      necessary over the long term to evaluate future nurse retention. The accurate
      workforce data provided by the Kenya Health Workforce Informatics System were
      essential for evaluating the effect of the Emergency Hiring Plan.

PMID- 21076564
TI  - Availability and quality of cause-of-death data for estimating the global burden
      of injuries.
AB  - OBJECTIVE: To assess the availability and quality of global death registration
      data used for estimating injury mortality. METHODS: The completeness and coverage
      of recent national death registration data from the World Health Organization
      mortality database were assessed. The quality of data on a specific cause of
      injury death was judged high if fewer than 20% of deaths were attributed to any
      of several partially specified causes of injury, such as "unspecified
      unintentional injury". FINDINGS: Recent death registration data were available
      for 83 countries, comprising 28% of the global population. They included most
      high-income countries, most countries in Latin America and several in central
      Asia and the Caribbean. Categories commonly used for partially specified external
      causes of injury resulting in death included "undetermined intent," "unspecified
      mechanism of unintentional injury," "unspecified road injury" and "unspecified
      mechanism of homicide". Only 20 countries had high-quality data. Nevertheless,
      because the partially specified categories do contain some information about
      injury mechanisms, reliable estimates of deaths due to specific external causes
      of injury, such as road injury, suicide and homicide, could be derived for many
      more countries. CONCLUSION: Only 20 countries had high-quality death registration
      data that could be used for estimating injury mortality because injury deaths
      were frequently classified using imprecise partially specified categories.
      Analytical methods that can derive national estimates of injury mortality from
      alternative data sources are needed for countries without reliable death
      registration systems.

PMID- 21076565
TI  - Nationwide survey on resource availability for implementing current sepsis
      guidelines in Mongolia.
AB  - OBJECTIVE: To assess if secondary and tertiary hospitals in Mongolia have the
      resources needed to implement the 2008 Surviving Sepsis Campaign (SSC)
      guidelines. METHODS: To obtain key informant responses, we conducted a nationwide
      survey by sending a 74-item questionnaire to head physicians of the intensive
      care unit or department for emergency and critically ill patients of 44 secondary
      and tertiary hospitals in Mongolia. The questionnaire inquired about the
      availability of the hospital facilities, equipment, drugs and disposable
      materials required to implement the SSC guidelines. Descriptive methods were used
      for statistical analysis. Comparisons between central and peripheral hospitals
      were performed using non-parametric tests. FINDINGS: The response rate was 86.4%
      (38/44). No Mongolian hospital had the resources required to consistently
      implement the SSC guidelines. The median percentage of implementable
      recommendations and suggestions combined was 52.8% (interquartile range, IQR:
      45.8-67.4%); of implementable recommendations only, 68% (IQR: 58.0-80.5%) and of
      implementable suggestions only, 43.5% (IQR: 34.8-57.6%). These percentages did
      not differ between hospitals located in the capital city and those located in
      rural areas. CONCLUSION: The results of this study strongly suggest that the most
      recent SSC guidelines cannot be implemented in Mongolia due to a dramatic
      shortage of the required hospital facilities, equipment, drugs and disposable
      materials. Further studies are needed on current awareness of the problem,
      development of national reporting systems and guidelines for sepsis care in
      Mongolia, as well as on the quality of diagnosis and treatment and of the
      training of health-care professionals.

PMID- 21076566
TI  - HIV infection in older adults in sub-Saharan Africa: extrapolating prevalence
      from existing data.
AB  - OBJECTIVE: To quantify the number of cases and prevalence of human
      immunodeficiency virus (HIV) infection among older adults in sub-Saharan Africa.
      METHODS: We reviewed data from Demographic and Health Surveys (DHS). Although in
      these surveys all female respondents are < 50 years of age, 18 of the surveys
      contained data on HIV infection among men aged >= 50 years. To estimate the
      percentage of older adults (i.e. people >= 50 years of age) who were positive for
      HIV (HIV+), we extrapolated from data from the Joint United Nations Programme on
      HIV/AIDS on the estimated number of people living with HIV and on HIV infection
      prevalence among adults aged 15-49 years. FINDINGS: In 2007, approximately 3
      million people aged >= 50 years were living with HIV in sub-Saharan Africa. The
      prevalence of HIV infection in this group was 4.0%, compared with 5.0% among
      those aged 15-49 years. Of the approximately 21 million people in sub-Saharan
      Africa aged >= 15 years that were HIV+, 14.3% were >= 50 years old. CONCLUSION:
      To better reflect the longer survival of people living with HIV and the ageing of
      the HIV+ population, indicators of the prevalence of HIV infection should be
      expanded to include people > 49 years of age. Little is known about comorbidity
      and sexual behaviour among HIV+ older adults or about the biological and cultural
      factors that increase the risk of transmission. HIV services need to be better
      targeted to respond to the growing needs of older adults living with HIV.

PMID- 21076567
TI  - Impact of a cash-for-work programme on food consumption and nutrition among women
      and children facing food insecurity in rural Bangladesh.
AB  - OBJECTIVE: To determine whether a cash-for-work programme during the annual food
      insecurity period in Bangladesh improved nutritional status in poor rural women
      and children. METHODS: The panel study involved a random sample of 895 households
      from over 50,000 enrolled in a cash-for-work programme between September and
      December 2007 and 921 similar control households. The height, weight and mid
      upper arm circumference of one woman and child aged less than 5 years from each
      household were measured at baseline and at the end of the study (mean time: 10
      weeks). Women reported 7-day household food expenditure and consumption on both
      occasions. Changes in parameters were compared between the two groups. FINDINGS:
      At baseline, no significant difference existed between the groups. By the study
      end, the difference in mean mid-upper arm circumference between women in the
      intervention and control groups had widened by 2.29 mm and the difference in mean
      weight, by 0.88 kg. Among children, the difference in means between the two
      groups had also widened in favour of the intervention group for: height (0.08 cm;
      P<0.05), weight (0.22 kg; P<0.001), mid-upper arm circumference (1.41 mm;
      P<0.001) and z-scores for height-for-age (0.02; P<0.001), weight-for-age (0.17;
      P<0.001), weight-for-height (0.23; P<0.001) and mid-upper arm circumference
      (0.12; P<0.001). Intervention households spent more on food and consumed more
      protein-rich food at the end of the study. CONCLUSION: The cash-for-work
      programme led to greater household food expenditure and consumption and women's
      and children's nutritional status improved.

PMID- 21076568
TI  - Lessons from New Zealand's introduction of pictorial health warnings on tobacco
      packaging.
AB  - While international evidence suggests that featuring pictorial health warnings on
      tobacco packaging is an effective tobacco control intervention, the process used
      to introduce these new warnings has not been well documented. We examined
      relevant documents and interviewed officials responsible for this process in New
      Zealand. We found that, despite tobacco companies' opposition to pictorial health
      warnings and the resource constraints facing health authorities, the
      implementation process was generally robust and successful. Potential lessons for
      other countries planning to introduce or refresh existing pictorial health
      warnings include: (i) strengthening the link between image research and policy;
      (ii) requiring frequent image development and refreshment; (iii) using larger
      pictures (e.g. 80% of the front of the packet); (iv) developing themes that
      recognize concerns held by different smoker sub-groups; and (v) running
      integrated mass media campaigns when the warnings are introduced. All countries
      could also support moves by the World Health Organization Framework Convention on
      Tobacco Control's Secretariat to develop an international bank of copyright-free
      warnings.

PMID- 21076569
TI  - Examining health-care volunteerism in a food- and financially-insecure world.

PMID- 21076570
TI  - Human cells and tissues: the need for a global ethical framework.

PMID- 21076571
TI  - Engaging with the water sector for public health benefits: waterborne pathogens
      and diseases in developed countries.

PMID- 21076573
TI  - Ubiquitous Diabetes Management System via Interactive Communication Based on
      Information Technologies: Clinical Effects and Perspectives.
AB  - New diabetes management systems based on interactive communication have been
      introduced recently, accompanying rapid advances in information technology; these
      systems are referred to as "ubiquitous diabetes management systems." In such
      ubiquitous systems, patients and medical teams can communicate via Internet or
      telecommunications, with patients uploading their glucose data and personal
      information, and medical teams sending optimal feedback. Clinical evidence from
      both long-term and short-term trials has been reported by some researchers. Such
      systems appear to be effective not only in reducing the levels of HbA1c but also
      in stabilizing glucose control. However, most notably, evidence for the cost
      effectiveness of such a system should be demonstrated before it can be propagated
      out to the general population in actual clinical practice. To establish a cost
      effective model, various types of clinical decision supporting software designed
      to reduce the labor time of physicians must first be developed. A number of
      sensors and devices for monitoring patients' data are expected to be available in
      the near future; thus, methods for automatic interconnections between devices and
      web charts were also developed. Further investigations to demonstrate the
      clinical outcomes of such a system should be conducted, hopefully leading to a
      new paradigm of diabetes management.

PMID- 21076574
TI  - Role of pyruvate dehydrogenase kinase 4 in regulation of blood glucose levels.
AB  - In the well-fed state a relatively high activity of the pyruvate dehydrogenase
      complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate
      into the citric acid cycle. In the fasted state a relatively low activity of the
      PDC helps maintain blood glucose levels by conserving pyruvate and other three
      carbon compounds for gluconeogenesis. The relative activities of the pyruvate
      dehydrogenase kinases (PDKs) and the opposing pyruvate dehydrogenase phosphatases
      determine the activity of PDC in the fed and fasted states. Up regulation of PDK4
      is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout
      mice have lower fasting blood glucose levels than wild type mice, proving that up
      regulation of PDK4 is important for normal glucose homeostasis. In type 2
      diabetes, up regulation of PDK4 also inactivates PDC, which promotes
      gluconeogenesis and thereby contributes to the hyperglycemia characteristic of
      this disease. When fed a high fat diet, wild type mice develop fasting
      hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up
      regulation of PDK4 contributes to hyperglycemia in diabetes. These finding
      suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.

PMID- 21076575
TI  - The association of brachial-ankle pulse wave velocity with acute postprandial
      hyperglycemia in korean prediabetic and diabetic subjects.

PMID- 21076576
TI  - The association of brachial-ankle pulse wave velocity with 30-minute post
      challenge plasma glucose levels in korean adults with no history of type 2
      diabetes.
AB  - BACKGROUND: Acute postprandial hyperglycemia is an important affector for
      atherosclerosis in subjects with glucose intolerance. We analyzed the
      relationship of brachial-ankle pulse wave velocity (baPWV) with fasting and post
      challenge plasma glucose levels according to different time points during oral
      glucose tolerance test (OGTT). METHODS: In 663 subjects with fasting
      hyperglycemia, 75 g OGTT were performed to confirm the glucose tolerant status,
      and fasting, post-challenge 30-minute and 120-minute glucose levels were
      measured. Anthropometric measurements were done, and fasting lipid profiles were
      measured. baPWV were measured in all subjects and the relationship between
      fasting, 30- and 120-minute post-challenge glucose levels and baPWV were
      analyzed. RESULTS: Among the participants, 62.9% were prediabetes and 31.7% were
      diabetes. Mean baPWV value was significantly higher in subjects with diabetes
      compared with prediabetes group. In bivariate correlation analyses, age, blood
      pressure, total cholesterol, low density lipoprotein cholesterol, 30-minute and
      120-minute post-challenge glucose levels showed significant positive correlation
      with baPWV value. In multiple regression analysis, 30-minute post-challenge
      glucose level was a weak but significant determinant for mean baPWV value even
      after adjustment for other confounding variables. CONCLUSIONS: Postprandial
      hyperglycemia, especially 30-minute glucose levels showed significant correlation
      with baPWV in subjects with fasting hyperglycemia. These results can imply the
      deleterious effect of acute hyperglycemic excursion on arterial stiffness in
      subjects with glucose intolerance.

PMID- 21076577
TI  - Bone mineral density in prediabetic men.
AB  - BACKGROUND: There are many studies regarding the effects of insulin on bone
      metabolism and changes in bone mineral density (BMD) in the setting of diabetes.
      The effect of prediabetes on BMD is not known. METHODS: A total of 802 men
      participated in the Korea Rural Genomic Cohort Study (in Geumsan County).
      According to the results of an oral glucose tolerance test, subjects were
      classified into normal, prediabetic, and diabetic categories. One hundred twenty
      four subjects diagnosed with type 2 diabetes were excluded, leaving 678 subjects
      for the study inclusion. BMD was estimated with a quantitative ultrasonometer.
      RESULTS: The average BMD T scores of normal and prediabetic subjects were -1.34
      +/- 1.42 and -1.33 +/- 1.30, respectively; there was no significant difference in
      the BMD T scores between these groups. The BMD T score was inversely associated
      with age and positively correlated with body weight, body mass index, total
      cholesterol, low density lipoprotein cholesterol, and HbA1c. On multiple linear
      regression analysis, low density lipoprotein cholesterol was the only
      statistically significant variable for prediabetes (beta = 0.007, P = 0.005). On
      the stepwise regression analysis, age (beta = -0.026, P < 0.001), the body mass
      index (beta = 0.079, P < 0.001), and low density lipoprotein cholesterol (beta =
      0.004, P = 0.016) were significant variables for prediabetes. CONCLUSIONS: There
      was no significant difference in the BMD T score between the normal and
      prediabetic subjects. Further studies are needed regarding the association of
      fracture risk and changes in BMD with the development of overt diabetes.

PMID- 21076578
TI  - A comparative study of diet in good and poor glycemic control groups in elderly
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Identification of dietary patterns is important for glycemic
      management in elderly patients with type 2 diabetes mellitus (T2DM). METHODS:
      Elderly T2DM patients (> 65 years of age, n = 48) were categorized based on their
      concentration of glycated hemoglobin (HbA(1c)). Subjects with HbA(1c) levels
      below 7% were placed in the good control (GC) group and those with HbA(1c) levels
      equal to or above 8% were placed in the poor control (PC) group. Anthropometric
      data, blood parameters, and dietary intake records were compared between the
      groups. Statistical analysis included Student's t-test, chi-square test, and
      Pearson correlation coefficient test. RESULTS: Anthropometric data, including
      body mass index (24.7 +/- 2.9 kg/m(2)), did not differ between the GC and PC
      groups. Significant abnormalities in blood glucose levels (P < 0.01), lean body
      mass (P < 0.01), and plasma protein and albumin levels (P < 0.05, P < 0.01) were
      found in the PC group. In contrast to the GC group, the PC group depended on
      carbohydrate (P = 0.014) rather than protein (P = 0.013) or fat (P = 0.005) as a
      major source of energy, and had a lower index of nutritional quality for
      nutrients such as protein (P = 0.001), and all vitamins and minerals (P < 0.001,
      0.01, or 0.05 for individual nutrients), except vitamin C, in their usual diet.
      Negative correlations between HbA(1c) levels and protein (r = -0.338, P < 0.05)
      or fat (r = -0.385, P < 0.01) intakes were also found. CONCLUSIONS: Healthcare
      professionals should encourage elderly diabetic patients to consume a balanced
      diet to maintain good glycemic control.

PMID- 21076579
TI  - The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene
      Expression in INS-1 Cells.
AB  - BACKGROUND: The highly developed endoplasmic reticulum (ER) structure in
      pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any
      perturbation in ER function inevitably impacts insulin biosynthesis. Recent
      studies showed that the expression of tribbles-related protein 3 (TRB3), a
      mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER
      stress. Here, we examined whether ER stress induces TRB3 expression in INS-1
      cells and found that TRB3 mediates ER stress-induced suppression of insulin gene
      expression. METHODS: The effects of tunicamycin and thapsigargin on insulin and
      TRB3 expression in INS-1 cells were measured by Northern and Western blot
      analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3
      on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by
      Northern blot analysis. The effect of TRB3 on insulin promoter was measured by
      transient transfection study with constructs of human insulin promoter. RESULTS:
      The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin
      mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated
      overexpression of TRB3 decreased insulin gene expression in a dose-dependent
      manner. A transient transfection study showed that TRB3 inhibited insulin
      promoter activity, suggesting that TRB3 inhibited insulin gene expression at
      transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased
      PDX-1 mRNA expression, but did not influence MafA mRNA expression. CONCLUSIONS:
      This study showed that ER stress induced TRB3 expression, but decreased both
      insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3
      plays an important role in ER stress-induced beta cell dysfunction.

PMID- 21076580
TI  - ENPP1 K121Q Genotype Not Associated with Coronary Artery Calcification in Korean
      Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates
      inorganic pyrophosphate, a solute that serves as an essential physiological
      inhibitor of calcification. Inactivating mutations of ENPP1 are associated with
      generalized calcification in infancy and an increased risk of developing type 2
      diabetes mellitus (T2DM). We hypothesized that the ENPP1 K121Q variant may be
      associated with increased coronary artery calcification in T2DM patients.
      METHODS: The study subjects were aged 34 to 85 years and showed no evidence of
      clinical cardiovascular disease prior to recruitment. A total of 140 patients
      with T2DM were assessed for their coronary artery calcium (CAC) scores and ENPP1
      K121Q polymorphisms were identified. RESULTS: The prevalence of subjects carrying
      the KQ genotype was 12.9% (n = 18). There were no 121QQ homozygotes. Patients
      with the KQ genotype did not show a significantly higher CAC score (122 vs. 18; P
      = 0.858). We matched each patient with the KQ genotype to a respective control
      with the KK genotype by gender, age, and duration of diabetes. When compared to
      matched controls, we observed no significant difference in CAC score (P = 0.959).
      CONCLUSIONS: The ENPP1 K121Q polymorphism does not appear to be associated with
      coronary artery calcification in patients with T2DM.

PMID- 21076581
TI  - Letter: The Relationship between Lung Function and Metabolic Syndrome in Obese
      and Non-Obese Korean Adult Males (Korean Diabetes J 2010;34:253-60).

PMID- 21076582
TI  - Response: The Relationship between Lung Function and Metabolic Syndrome in Obese
      and Non-Obese Korean Adult Males (Korean Diabetes J 2010;34:253-60).

PMID- 21076583
TI  - Supplementary screening sonography in mammographically dense breast: pros and
      cons.
AB  - Sonography is an attractive supplement to mammography in breast cancer screening
      because it is relatively inexpensive, requires no contrast-medium injection, is
      well tolerated by patients, and is widely available for equipment as compared
      with MRI. Sonography has been especially valuable for women with mammographically
      dense breast because it has consistently been able to detect a substantial number
      of cancers at an early stage. Despite these findings, breast sonography has known
      limitations as a screening tool; operator-dependence, the shortage of skilled
      operators, the inability to detect microcalcifications, and substantially higher
      false-positive rates than mammography. Further study of screening sonography is
      still ongoing and is expected to help establish the role of screening sonography.

PMID- 21076584
TI  - Role of duplex power Doppler ultrasound in differentiation between malignant and
      benign thyroid nodules.
AB  - OBJECTIVE: To evaluate the usage of duplex power Doppler ultrasound (PDUS) for
      the differentiation of benign and malignant thyroid nodules. MATERIALS AND
      METHODS: We prospectively examined 77 thyroid nodules in 60 patients undergoing
      ultrasound-guided fine needle aspiration biopsy (FNAB). Each nodule was described
      according to size, inner structure, borders, parenchymal echogenicity, peripheral
      halo formation, and the presence of calcification (B-mode ultrasound findings).
      Vascularity as determined by PDUS imaging was defined as non-vascular,
      peripheral, central, or of mixed type. For each nodule, the pulsatility index
      (PI) and resistive index (RI) values were obtained. Results of FNAB and surgical
      pathological examination (if available) were used as a proof of final diagnosis
      to categorize all nodules as benign or malignant. A receiver operating
      characteristic (ROC) curve analysis was performed to establish cut-off,
      sensitivity, and specificity values associated with RI-PI values. RESULTS: A
      significant relationship was observed between malignancy and irregular margins,
      microcalcifications, and hypoechogenicity on ultrasound examination (p < 0.05).
      The pattern of vascularity as determined by PDUS analysis was not a statistically
      significant criterion to suggest benign or malignant disease in this study (p >
      0.05). The central, peripheral, and mean RI-PI values were higher in malignant
      nodules when compared to the other cytologies (p < 0.05). CONCLUSION: Vascularity
      is not a useful parameter for distinguishing malignant from benign thyroid
      nodules. However, RI and PI values are useful in distinguishing malignant from
      benign thyroid nodules.

PMID- 21076585
TI  - Endovascular treatment of traumatic pseudoaneurysm presenting as intractable
      epistaxis.
AB  - OBJECTIVE: To investigate the clinical efficacy of individual endovascular
      management for the treatment of different traumatic pseudoaneurysms presenting as
      intractable epistaxis. MATERIALS AND METHODS: For 14 consecutive patients with
      traumatic pseudoaneurysm presenting as refractory epistaxes, 15 endovascular
      procedures were performed. Digital subtraction angiography revealed that the
      pseudoaneurysms originated from the internal maxillary artery in eight patients;
      and all were treated with occlusion of the feeding artery. In six cases, they
      originated from the internal carotid artery (ICA); out of which, two were managed
      with detachable balloons, two with covered stents, one by means of cavity
      embolization, and the remaining one with parent artery occlusion. All of these
      cases were followed up clinically from six to 18 months, with a mean follow up
      time of ten months; moreover, three cases were also followed with angiography.
      RESULTS: Complete cessation of bleeding was achieved in all the 15 instances
      (100%) immediately after the endovascular therapies. Of the six patients who
      suffered from ICA pseudoaneurysms, one presented with a permanent stroke and one
      had an episode of rebleeding requiring intervention. CONCLUSION: In patients
      presenting with a history of craniocerebral trauma, traumatic pseudoaneurysm must
      be considered as a differential diagnosis. Individual endovascular treatment is a
      relatively safe, plausible, and reliable means of managing traumatic
      pseudoaneurysms.

PMID- 21076586
TI  - Chest radiographic findings in primary pulmonary tuberculosis: observations from
      high school outbreaks.
AB  - OBJECTIVE: To describe the radiographic findings of primary pulmonary
      tuberculosis (TB) in previously healthy adolescent patients. MATERIALS AND
      METHODS: The Institutional Review Board approved this retrospective study, with a
      waiver of informed consent from the patients. TB outbreaks occurred in 15 senior
      high schools and chest radiographs from 58 students with identical strains of TB
      were analyzed by restriction fragment length polymorphism analysis by two
      independent observers. Lesions of nodule(s), consolidation, or cavitation in the
      upper lung zones were classified as typical TB. Mediastinal lymph node
      enlargement; lesions of nodule(s), consolidation, or cavitation in lower lung
      zones; or pleural effusion were classified as atypical TB. Inter-observer
      agreement for the presence of each radiographic finding was examined by kappa
      statistics. RESULTS: Of 58 patients, three (5%) had normal chest radiographs.
      Cavitary lesions were present in 25 (45%) of 55 students. Lesions with upper lung
      zone predominance were observed in 27 (49%) patients, whereas lower lung zone
      predominance was noted in 18 (33%) patients. The remaining 10 (18%) patients had
      lesions in both upper and lower lung zones. Pleural effusion was not observed in
      any patient, nor was the mediastinal lymph node enlargement. Hilar lymph node
      enlargement was seen in only one (2%) patient. Overall, 37 (67%) students had the
      typical form of TB, whereas 18 (33%) had TB lesions of the atypical form.
      CONCLUSION: The most common radiographic findings in primary pulmonary TB by
      recent infection in previously healthy adolescents are upper lung lesions, which
      were thought to be radiographic findings of reactivation pulmonary TB by remote
      infection.

PMID- 21076587
TI  - Molecularly targeted therapy using bevacizumab for non-small cell lung cancer: a
      pilot study for the new CT response criteria.
AB  - OBJECTIVE: We wanted to compare the efficacy of the new CT response evaluation
      criteria for predicting the tumor progression-free survival (PFS) with that of
      RECIST 1.1 in non-small cell lung cancer (NSCLC) patients who were treated with
      bevacizumab. MATERIALS AND METHODS: Sixteen patients (M:F = 11:5; median age, 57
      years) treated with bevacizumab and combined cytotoxic chemotherapeutic agents
      were selected for a retrospective analysis. The tumor response was assessed by
      four different methods, namely, by using RECIST 1.1 (RECIST), RECIST but
      measuring only the solid component of tumor (RECISTsolid), the alternative method
      reflecting tumor cavitation (the alternative method) and the combined criteria
      (the combined criteria) that evaluated both the changes of tumor size and
      attenuation. To evaluate the capabilities of the different measurement methods to
      predict the patient prognosis, the PFS were compared, using the log rank test,
      among the responder groups (complete response [CR], partial response [PR], stable
      disease [SD] and progressive disease [PD]) in terms of the four different
      methods. RESULTS: The overall (CR, PR or SD) response rates according to RECIST,
      RECISTsolid, the alternative method and the combined criteria were 81%, 88%, 81%
      and 85%, respectively. The confirmed response rates (CR or PR) were 19%, 19%, 50%
      and 54%, respectively. Although statistically not significant, the alternative
      method showed the biggest difference for predicting PFS among the three response
      groups (PR, SD and PD) (p = 0.07). RECIST and the alternative method showed a
      significant difference for predicting the prognosis between the good (PR or SD)
      and poor overall responders (p = 0.02). CONCLUSION: The response outcome
      evaluations using the three different CT response criteria that reflect tumor
      cavitation, the ground-glass opacity component and the attenuation changes in
      NSCLC patients treated with bevacizumab showed different results from that with
      using the traditional RECIST method.

PMID- 21076588
TI  - Abnormal motion of the interventricular septum after coronary artery bypass graft
      surgery: comprehensive evaluation with MR imaging.
AB  - OBJECTIVE: To define the mechanism associated with abnormal septal motion (ASM)
      after coronary artery bypass graft surgery (CABG) using comprehensive MR imaging
      techniques. MATERIALS AND METHODS: Eighteen patients (mean age, 58 +/- 12 years;
      15 males) were studied with comprehensive MR imaging using rest/stress perfusion,
      rest cine, and delayed enhancement (DE)-MR techniques before and after CABG.
      Myocardial tagging was also performed following CABG. Septal wall motion was
      compared in the ASM and non-ASM groups. Preoperative and postoperative results
      with regard to septal wall motion in the ASM group were also compared. We then
      analyzed circumferential strain after CABG in both the septal and lateral walls
      in the ASM group. RESULTS: All patients had normal septal wall motion and
      perfusion without evidence of non-viable myocardium prior to surgery.
      Postoperatively, ASM at rest and/or stress state was documented in 10 patients
      (56%). However, all of these had normal rest/stress perfusion and DE findings at
      the septum. Septal wall motion after CABG in the ASM group was significantly
      lower than that in the non-ASM group (2.1+/-5.3 mm vs. 14.9+/-4.7 mm in the non
      ASM group; p < 0.001). In the ASM group, the degree of septal wall motion showed
      a significant decrease after CABG (preoperative vs. postoperative = 15.8+/-4.5 mm
      vs. 2.1+/-5.3 mm; p = 0.007). In the ASM group after CABG, circumferential
      shortening of the septum was even larger than that of the lateral wall (-20.89+/
      5.41 vs. -15.41+/-3.7, p < 0.05) CONCLUSION: Abnormal septal motion might not be
      caused by ischemic insult. We suggest that ASM might occur due to an increase in
      anterior cardiac mobility after incision of the pericardium.

PMID- 21076589
TI  - Value of power Doppler and gray-scale US in the diagnosis of carpal tunnel
      syndrome: contribution of cross-sectional area just before the tunnel inlet as
      compared with the cross-sectional area at the tunnel.
AB  - OBJECTIVE: To determine the value of gray-scale and power Doppler ultrasonography
      in the evaluation of carpal tunnel syndrome (CTS). MATERIALS AND METHODS: Median
      nerves at the carpal tunnel were evaluated by using gray-scale and power Doppler
      ultrasonography and by using accepted and new criteria in 42 patients with CTS
      (62 wrists) confirmed by electromyogram and 33 control subjects. We evaluated the
      cross-sectional area of the nerve just proximal to the tunnel inlet (CSAa), and
      at mid level (CSAb). We then calculated the percentage area increase of CSAb, and
      area difference (CSAb-CSAa). We measured two dimensions of the nerve at the
      distal level to calculate the flattening ratio. The power Doppler ultrasonography
      was used to assess the number of vessels, which proceeded to give a score
      according to the vessel number, and lastly evaluated the statistical significance
      by comparing the means of patients with control subjects by the Student t test
      for independent samples. Sensitivities and specificities were determined for
      sonographic characteristics mentioned above. We obtained the receiver operating
      characteristic (ROC) curve to assess the optimal cut-off values for the diagnosis
      of CTS. RESULTS: A statistically significant difference was found between
      patients and the control group for mean CSAb, area difference, percentage area
      increase, and flattening ratio (p < 0.001, p < 0.001, p < 0.001, p < 0.05,
      respectively). From the ROC curve we obtained optimal cut-off values of 11 mm(2)
      for CSAb, 3.65 for area difference, 50% for the percentage of area increase, and
      2.6 for the flattening ratio. The mean number of vessels obtained by power
      Doppler ultrasonography from the median nerve was 1.2. We could not detect
      vessels from healthy volunteers. Mean CSAbs related to vascularity intensity
      scores were as follows: score 0: 12.3 +/- 2.8 mm(2), score 1: 12.3 +/- 3.1 mm(2),
      score 2: 14.95 +/- 3.5 mm(2), score 3: 19.3 +/- 3.8 mm(2). The mean PI value in
      vessels of the median nerve was 4.1 +/- 1. CONCLUSION: Gray-scale and power
      Doppler ultrasonography are useful in the evaluation of CTS.

PMID- 21076590
TI  - Case study of hepatic radiofrequency ablation causing a systemic inflammatory
      response under total intravenous anesthesia.
AB  - OBJECTIVE: To investigate the effects of hepatic radiofrequency ablation (RFA) in
      patients with malignant liver disease with respect to inflammation activation and
      stress response. MATERIALS AND METHODS: In an observational trial, we
      investigated the physiologic parameters of 17 patients (20 interventions) who
      underwent percutaneous RFA under general anesthesia after applying total
      intravenous anesthesia. TNFalpha, IL-6, IL-8, IL-10, adrenaline and
      noradrenaline, liver enzymes, lactate and creatine kinase were determined pre
      interventionally after induction of anesthesia (T1), 90 minutes after initiation
      of RFA (T2), immediately after the conclusion of the procedure (T3), and 24 hours
      after the procedure (T4). RESULTS: A significant increase in body temperature (p
      < 0.001), and mean arterial pressure (p = 0.001) were measured intraoperatively
      (T2) and the day after the procedure (T4). Increased levels of IL-6 were measured
      at T3 and T4 (p = 0.001). IL-10 increased immediately after the procedure (T3; p
      = 0.007). IL-6 levels correlated well with the total energy applied (r = 0.837).
      Significant increases in the levels of adrenaline and noradrenaline were present
      at T3 and T4 (p < 0.001). The RFA-induced destruction of hepatic tissue was
      associated with increased levels of AST, ALT, GLDH and LDH. CONCLUSION:
      Percutaneous RFA of hepatic malignancies causes an inflammatory and endocrine
      activation, similar to the systemic inflammatory response syndrome. These effects
      have to be taken in account when dealing with patients susceptible to sepsis or
      multi-organ failure.

PMID- 21076591
TI  - A simplified technique of percutaneous hepatic artery port-catheter insertion for
      the treatment of advanced hepatocellular carcinoma with portal vein invasion.
AB  - OBJECTIVE: We assessed the outcomes of a simplified technique for the
      percutaneous placement of a hepatic artery port-catheter system for chemotherapy
      infusion in advanced hepatocellular carcinoma with portal vein invasion.
      MATERIALS AND METHODS: From February 2003 to February 2008, percutaneous hepatic
      artery port-catheter insertion was performed in 122 patients who had
      hepatocellular carcinoma with portal vein invasion. The arterial access route was
      the common femoral artery. The tip of the catheter was wedged into the right
      gastroepiploic artery without an additional fixation device. A side hole was
      positioned at the distal common hepatic artery to allow the delivery of
      chemotherapeutic agents into the hepatic arteries. Coil embolization was
      performed only to redistribute to the hepatic arteries or to prevent the
      inadvertent delivery of chemotherapeutic agents into extrahepatic arteries. The
      port chamber was created at either the supra-inguinal or infra-inguinal region.
      RESULTS: Technical success was achieved in all patients. Proper positioning of
      the side hole was checked before each scheduled chemotherapy session by port
      angiography. Catheter-related complications occurred in 19 patients (16%).
      Revision was achieved in 15 of 18 patients (83%). CONCLUSION: This simplified
      method demonstrates excellent technical feasibility, an acceptable range of
      complications, and is hence recommended for the management of advanced
      hepatocellular carcinoma with portal vein thrombosis.

PMID- 21076592
TI  - Novel influenza A (H1N1) virus infection in children: chest radiographic and CT
      evaluation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the chest radiographic and
      CT findings of novel influenza A (H1N1) virus infection in children, the
      population that is more vulnerable to respiratory infection than adults.
      MATERIALS AND METHODS: The study population comprised 410 children who were
      diagnosed with an H1N1 infection from August 24, 2009 to November 11, 2009 and
      underwent chest radiography at Dankook University Hospital in Korea. Six of these
      patients also underwent chest CT. The initial chest radiographs were classified
      as normal or abnormal. The abnormal chest radiographs and high resolution CT
      scans were assessed for the pattern and distribution of parenchymal lesions, and
      the presence of complications such as atelectasis, pleural effusion, and
      pneumomediastinum. RESULTS: The initial chest radiograph was normal in 384 of 410
      (94%) patients and abnormal in 26 of 410 (6%) patients. Parenchymal abnormalities
      seen on the initial chest radiographs included prominent peribronchial marking
      (25 of 26, 96%), consolidation (22 of 26, 85%), and ground-glass opacities
      without consolidation (2 of 26, 8%). The involvement was usually bilateral (19 of
      26, 73%) with the lower lung zone predominance (22 of 26, 85%). Atelectasis was
      observed in 12 (46%) and pleural effusion in 11 (42%) patients. CT (n = 6) scans
      showed peribronchovascular interstitial thickening (n = 6), ground-glass
      opacities (n = 5), centrilobular nodules (n = 4), consolidation (n = 3),
      mediastinal lymph node enlargement (n = 5), pleural effusion (n = 3), and
      pneumomediastinum (n = 3). CONCLUSION: Abnormal chest radiographs were uncommon
      in children with a swine-origin influenza A (H1N1) virus (S-OIV) infection. In
      children, H1N1 virus infection can be included in the differential diagnosis,
      when chest radiographs and CT scans show prominent peribronchial markings and ill
      defined patchy consolidation with mediastinal lymph node enlargement, pleural
      effusion and pneumomediastinum.

PMID- 21076593
TI  - Clinical application of liver MR imaging in Wilson's disease.
AB  - OBJECTIVE: To determine whether there is a correlation between liver MR findings
      and the clinical manifestations and severity of liver dysfunction in patients
      with Wilson's disease. MATERIALS AND METHODS: Two radiologists retrospectively
      evaluated MR images of the liver in 50 patients with Wilson's disease. The
      Institutional Review Board approved this retrospective study and informed consent
      was waived. MR images were evaluated with a focus on hepatic contour
      abnormalities and the presence of intrahepatic nodules. By using Fisher's exact
      test, MR findings were compared with clinical presentations (neurological and non
      neurological) and hepatic dysfunction, which was categorized by the Child-Pugh
      classification system (A, B and C). Follow-up MR images were available for 17
      patients. RESULTS: Contour abnormalities of the liver and intrahepatic nodules
      were observed in 31 patients (62%) and 25 patients (50%), respectively. Each MR
      finding showed a statistically significant difference (p < 0.05) among the three
      groups of Child-Pugh classifications (A, n = 36; B, n = 5; C, n = 9), except for
      splenomegaly (p = 0.243). The mean age of the patients with positive MR findings
      was higher than that of patients with negative MR findings. For patients with
      Child-Pugh class A (n = 36) with neurological presentation, intrahepatic nodules,
      surface nodularity, and gallbladder fossa widening were more common. Intrahepatic
      nodules were improved (n = 8, 47%), stationary (n = 5, 29%), or aggravated (n =
      4, 24%) on follow-up MR images. CONCLUSION: MR imaging demonstrates the contour
      abnormalities and parenchymal nodules of the liver in more than half of the
      patients with Wilson's disease, which correlates with the severity of hepatic
      dysfunction and clinical manifestations.

PMID- 21076594
TI  - Evaluation of porcine pancreatic islets transplanted in the kidney capsules of
      diabetic mice using a clinically approved superparamagnetic iron oxide (SPIO) and
      a 1.5T MR scanner.
AB  - OBJECTIVE: To evaluate transplanted porcine pancreatic islets in the kidney
      capsules of diabetic mice using a clinically approved superparamagnetic iron
      oxide (SPIO) and a 1.5T MR scanner. MATERIALS AND METHODS: Various numbers of
      porcine pancreatic islets labeled with Resovist, a carboxydextran-coated SPIO,
      were transplanted into the kidney capsules of normal mice and imaged with a 3D
      FIESTA sequence using a 1.5T clinical MR scanner. Labeled (n = 3) and unlabeled
      (n = 2) islets were transplanted into the kidney capsules of streptozotocin
      induced diabetic mice. Blood glucose levels and MR signal intensities were
      monitored for 30 days post-transplantation. RESULTS: There were no significant
      differences in viability or insulin secretion between labeled and unlabeled
      islets. A strong correlation (r(2) > 0.94) was evident between the number of
      transplanted islets and T(2) relaxation times quantified by MRI. Transplantation
      with labeled or unlabeled islets helped restore normal sustained glucose levels
      in diabetic mice, and nephrectomies induced the recurrence of diabetes. The MR
      signal intensity of labeled pancreatic islets decreased by 80% over 30 days.
      CONCLUSION: The transplantation of SPIO-labeled porcine islets into the kidney
      capsule of diabetic mice allows to restore normal glucose levels, and these
      islets can be visualized and quantified using a 1.5T clinical MR scanner.

PMID- 21076595
TI  - A rare case of recurrent myoid hamartoma mimicking malignancy: imaging
      appearances.
AB  - Myoid hamartoma is an uncommon type of breast hamartoma and its recurrence is
      very rare. We report the imaging appearance of an unusual case of recurrent myoid
      hamartoma of the breast mimicking malignancy in a 43-year-old woman. Although the
      mammographic and ultrasonographic findings have long been described in the
      literature, MR finding with a dynamic study has not, to the best of our
      knowledge, been reported previously.

PMID- 21076596
TI  - Invasive ductal carcinoma in a mammary hamartoma: case report and review of the
      literature.
AB  - Mammary hamartomas are typically a benign condition and rarely develop into
      malignant lesions. Only 14 cases of carcinomas associated with a hamartoma have
      been documented in the literature. In this case report, we describe a case of
      invasive ductal carcinoma within a hamartoma in a 72-year-old woman. Mammography,
      ultrasonography, and magnetic resonance imaging showed the features of a typical
      hamartoma with a suspicious mass arising in it. This case illustrates the
      importance of identification of unusual findings in a typical mammary hamartoma
      on radiologic examinations.

PMID- 21076597
TI  - Epithelioid hemangioma involving three contiguous bones: a case report with a
      review of the literature.
AB  - An epithelioid hemangioma involving three contiguous bones in continuity has, to
      the best of our knowledge, not been reported in the literature. A case of a 48
      year-old man presented with radiating pain to the lower thoracic region for two
      years. A radiograph and CT scan revealed both permeative osteolytic and multiple
      trabeculated lesions involving the left posterior part of the 10th rib as well as
      the 9th and 10th vertebral bodies in continuity and was misled as a malignant or
      infectious lesion. The histopathology and immuno-histochemistry of the lesion
      confirmed the diagnosis of an epithelioid hemangioma. The lesion was still stable
      as of three years after surgery.

PMID- 21076598
TI  - Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma presenting
      as a submucosal mass: CT findings with pathologic correlation.
AB  - A lymphoepithelioma-like carcinoma, characterized by a carcinoma with heavy
      lymphocyte infiltration, is one of the histological patterns observed in patients
      with Epstein-Barr virus (EBV)-associated gastric carcinoma. Less than half of
      invasive carcinomas with lymphoepithelioma-like histology can grow to make a
      submucosal mass. These tumors generally have a better prognosis than conventional
      adenocarcinomas. We report a case of an EBV-associated lymphoepithelioma-like
      gastric carcinoma that presented as a submucosal mass on multi-detector (MD) CT
      and correlate them with the pathology.

PMID- 21076599
TI  - Correspondence re: recanalization of an occluded intrahepatic portosystemic
      covered stent via the percutaneous transhepatic approach.

PMID- 21076600
TI  - Correspondence re: MRI findings of primary CNS lymphoma in 26 immunocompetent
      patients.

PMID- 21076601
TI  - Chemoendocrine Treatment Is Standard in Hormone Receptor-Positive Patients.

PMID- 21076602
TI  - Is Chemoendocrine Treatment without Alternative?

PMID- 21076604
TI  - Node-positive Breast Cancer: Which Are the Best Chemotherapy Regimens?
AB  - Breast cancer-associated mortality has been significantly reduced since the
      1990s, mainly because of early diagnosis and systemic therapeutic interventions.
      All three therapy components - cytostatic therapy, endocrine therapy and targeted
      antibody therapy - are at present necessary tools for the curative treatment of
      primary breast cancer. This article reviews the evidence base for the use of
      various chemotherapy schedules in patients with primary, node-positive breast
      cancer, including schedules in combination with targeted HER2/neu therapy.

PMID- 21076603
TI  - Node-Negative Breast Cancer: Which Patients Should Be Treated?
AB  - Adjuvant systemic therapy has led to markedly improved outcome in early-stage
      breast cancer. However, the absolute gains from chemotherapy might be modest in
      node-negative patients. Adjuvant chemotherapy is the only option for triple
      negative breast cancer patients and should be used with trastuzumab in HER2
      positive patients. Considering the large group of patients with some degree of
      endocrine responsiveness, adding chemotherapy according to risk is an option. At
      present, we guide our therapeutic decisions using clinicopathologic risk
      classifications like the St. Gallen risk category or Adjuvant! online. A downside
      of these risk estimations is a low specificity and consequently the risk for
      overtreatment of a considerable number of patients. To spare patients unnecessary
      toxicities we need more reliable prognostic factors or tumor markers. From the
      plethora of tumor markers, only urokinase-type plasminogen activator
      (uPA)/plasminogen activator inhibitor 1 (PAI-1) and certain multiparameter gene
      expression assays are recommended by the American Society of Clinical Oncology.
      These tumor markers are presently investigated in clinical trials in node
      negative breast cancer (NNBC-3, MINDACT, TAILORx). These studies will hopefully
      allow us to quantify the risk of progression in the individual patient and to
      tailor treatment accordingly. This should lead to a more personalized treatment
      recommendation.

PMID- 21076605
TI  - Dose-Dense Chemotherapy: Principles, Clinical Results and Future Perspectives.
AB  - The dose intensity of adjuvant chemotherapy for breast cancer is an important
      predictor of clinical outcome. Dose-dense chemotherapy increases the dose
      intensity of the regimen by delivering standard-dose chemotherapy with shorter
      intervals between the treatment cycles. The rationale for dose-dense therapy
      stems from the Norton-Simon hypothesis: Sequential, consecutive dosing of
      chemotherapy using single or a combination of agents increases the dose density
      over alternating dosing, improving results. Supporting adjuvant studies, such as
      C9741, and the ensuing clinical experience indicate an improved disease-free and
      overall survival. Dosedense adjuvant chemotherapy improves clinical outcomes
      without increasing toxicity.

PMID- 21076606
TI  - Targeted Therapy: Can It Substitute for Chemotherapy?
AB  - Every oncologist has a dream - doing more with less toxicity. Targeted therapies
      seem to be the key for an oncologist's dreams by defining subgroups of those
      patients who benefit more from a specific treatment and those who do not. For a
      few years now, targeted therapies have played a major role in the treatment of
      primary as well as metastatic breast cancer. In this article, we describe
      targeted therapies that already play an important role in clinical decisions in
      the treatment of metastatic as well as primary breast cancer. The humanised
      monoclonal antibody trastuzumab is a very effective agent in primary and
      metastatic breast cancer, but only for those patients whose tumours are
      overexpressing HER2/neu. Bevacizumab is an antibody directed against vascular
      epidermal growth factor ligand A which plays a role in angiogenesis. Up to now
      there is no predictive factor known for this treatment. Furthermore, we would
      like to give an impression of new agents and strategies under investigation like
      tyrosine kinase inhibitors and other small molecules.

PMID- 21076607
TI  - Combined Chemotherapy with Mitomycin C, Folinic Acid, and 5-Fluorouracil (MiFoFU)
      as Salvage Treatment for Patients with Liver Metastases from Breast Cancer - a
      Retrospective Analysis.
AB  - BACKGROUND: The aim of this study was to analyze the activity and tolerability of
      a combined chemotherapy with mitomycin C, folinic acid, and 5-fluorouracil
      (MiFoFU) in patients with hepatic metastases from breast cancer, and in
      particular in patients with impaired liver function. PATIENTS AND METHODS: We
      retrospectively studied the charts of 44 patients who were treated with a MiFoFU
      combination therapy because of progressive metastatic breast cancer. Predominant
      site of metastases was the liver. Primary endpoints were response and time to
      progression (TTP); secondary endpoints were overall survival (OS) and
      tolerability. RESULTS: Median age prior to treatment was 59 years. A median of 6
      treatment cycles were administered per patient. Clinical benefit rate amounted to
      64%. A mean TTP of 9 months and a mean OS of 14 months were found. Main clinical
      signs of nonhematological toxicity were stomatitis, nausea, and diarrhea. Grade
      III/IV hematotoxicity was seen in only 9 patients. 16 patients showed clinical
      signs of liver dysfunction. A clinical benefit could be achieved in 8 of these
      patients. CONCLUSION: MiFoFU combination chemotherapy is a well-tolerated
      treatment alternative in the palliative therapy of patients with liver metastases
      from breast cancer. Particularly in patients with hepatic dysfunction, this
      regimen seems to represent a helpful treatment option.

PMID- 21076608
TI  - Chyle Fistula after Neck Dissection for an Unusual Breast Cancer Recurrence.
AB  - BACKGROUND: Chyle fistula is one of the rare complications of neck dissections.
      Even though no consented algorithm for the management of this entity has been
      established yet, conservative treatment options including somatostatin analogues
      have been suggested as an adequate modality for low output fistulas. CASE REPORT:
      Here we present a patient with a right-sided neck fistula which was resistant to
      conventional treatment, and was finally treated by surgery. The neck dissection
      was performed for a malignant right neck mass that was accepted as the lymph node
      metastasis of formerly treated papillary thyroid carcinoma. The pathology of the
      specimen revealed a contralateral neck metastasis of previously treated breast
      carcinoma. CONCLUSION: We assume that consecutive surgeries on axillary and neck
      lymph pathways resulted in such a complicated and exceptional case.

PMID- 21076609
TI  - Axillary Web Syndrome after Sentinel Node Biopsy.
AB  - BACKGROUND: Axillary web syndrome (AWS) is a self-limiting cause of morbidity in
      the early postoperative period after axillary surgery, but it is encountered also
      after sentinel lymph node biopsy. The syndrome is characterized by cords of
      subcutaneous tissue extending from the axilla into the medial arm. CASE REPORT:
      Here, we report a patient presenting with AWS several weeks after sentinel lymph
      node biopsy. CONCLUSION: AWS has been reported to be resolved spontaneously in
      all patients 8-16 weeks after axillary surgery, and shoulder movements improve in
      this period. There is no definitive treatment modality for AWS. Patients should
      be reassured and informed that this condition will improve even without
      treatment.

PMID- 21076610
TI  - The Academic Division of Breast and Gynaecological Oncology of the Institute for
      Cancer Research and Treatment (IRCC) of Candiolo, Turin, Italy.

PMID- 21076611
TI  - Neckties and cerebrovascular reactivity in young healthy males: a pilot
      randomised crossover trial.
AB  - Background. A necktie may elevate intracranial pressure through compression of
      venous return. We hypothesised that a tight necktie would deleteriously alter
      cerebrovascular reactivity. Materials and Methods. A necktie was simulated using
      bespoke apparatus comprising pneumatic inner-tube with aneroid pressure-gauge.
      Using a randomised crossover design, cerebrovascular reactivity was measured with
      the "pseudo-tie" worn inflated or deflated for 5 minutes (simulating tight/loose
      necktie resp.). Reactivity was calculated using breath hold index (BHI) and
      paired "t" testing used for comparative analysis. Results. We enrolled 40 healthy
      male volunteers. There was a reduction in cerebrovascular reactivity of 0.23
      units with "tight" pseudotie (BHI loose 1.44 (SD 0.48); BHI tight 1.21 (SD 0.38)
      P < .001). Conclusion. Impairment in cerebrovascular reactivity was found with
      inflated pseudo-tie. However, mean BHI is still within a range of considered
      normal. The situation may differ in patients with vascular risk factors, and
      confirmatory work is recommended.

PMID- 21076612
TI  - GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen
      activator gene expression.
AB  - GATA6 is a zinc finger transcription factor expressed in the colorectal
      epithelium. We have examined the expression of GATA6 in colon cancers and
      investigated the mechanisms by which GATA6 regulates colon cancer cell invasion.
      GATA6 was overexpressed in colorectal polyps and primary and metastatic tumors.
      GATA6 was strongly expressed in both the nuclear and cytoplasmic compartments of
      the colon cancer cells. GATA6 expression was upregulated in invasive HT29 and
      KM12L4 cells compared with the parental HT29 and KM12 cells and positively
      correlated with urokinase-type plasminogen activator (uPA) gene expression. Small
      interfering RNA (siRNA) knockdown of GATA6 resulted in reduced uPA gene
      expression and cell invasion. GATA6 bound to the uPA gene regulatory sequences in
      vivo and activated uPA promoter activity in vitro. uPA promoter deletion analysis
      indicated that the promoter proximal Sp1 sites were required for GATA6 activation
      of the uPA promoter. Accordingly, GATA6 physically associated with Sp1 and siRNA
      knockdown of Sp1 decreased GATA6 activation of the uPA promoter activity
      suggesting that Sp1 recruits GATA6 to the uPA promoter and mediates GATA6 induced
      activation of the uPA promoter activity. On the basis of our results, we conclude
      that GATA6 is an important regulator of uPA gene expression, and the dysregulated
      expression of GATA6 contributes to colorectal tumorigenesis and tumor invasion.

PMID- 21076615
TI  - Loss of STAT1 from mouse mammary epithelium results in an increased Neu-induced
      tumor burden.
AB  - Type I and type II classes of interferons (IFNs) signal through the JAK/STAT1
      pathway and are known to be important in adaptive and innate immune responses and
      in protection against tumors. Although STAT1 is widely considered a tumor
      suppressor, it remains unclear, however, if this function occurs in tumor cells
      (cell autonomous) or if STAT1 acts primarily through immune cells. Here, the
      question of whether STAT1 has a cell autonomous role in mammary tumor formation
      was addressed in a mouse model of ERBB2/neu-induced breast cancer in the absence
      and presence of STAT1. For this purpose, mice that carry floxed Stat1 alleles,
      which permit cell-specific removal of STAT1, were generated. To induce tumors
      only in mammary cells lacking STAT1, Stat1 floxed mice were crossed with
      transgenic mice that express cre recombinase and the neu oncogene under the mouse
      mammary tumor virus LTR (Stat1fl/fl NIC). Stat1 was effectively deleted in
      mammary epithelium of virgin Stat1fl/fl NIC females. Time-to-tumor onset was
      significantly shorter in Stat1fl/fl NIC females than in WT NIC (Wilcoxon rank sum
      test, P = .02). The median time-to-tumor onset in the Stat1fl/fl NIC mice was
      49.4 weeks, whereas it was 62.4 weeks in the WT NIC mice. These results suggest
      that STAT1 in mammary epithelial cells may play a role in suppressing
      tumorigenesis. The Stat1 floxed allele described in this study is also a unique
      resource to determine the cellular targets of IFNs and STAT1 action, which should
      aid our understanding and appreciation of these pathways.

PMID- 21076613
TI  - Down-regulation of microRNAs 222/221 in acute myelogenous leukemia with deranged
      core-binding factor subunits.
AB  - Core-binding factor leukemia (CBFL) is a subgroup of acute myeloid leukemia (AML)
      characterized by genetic mutations involving the subunits of the core-binding
      factor (CBF). The leukemogenesis model for CBFL posits that one, or more, gene
      mutations inducing increased cell proliferation and/or inhibition of apoptosis
      cooperate with CBF mutations for leukemia development. One of the most common
      mutations associated with CBF mutations involves the KIT receptor. A high
      expression of KIT is a hallmark of a high proportion of CBFL. Previous studies
      indicate that microRNA (MIR) 222/221 targets the 3' untranslated region of the
      KIT messenger RNA and our observation that AML1 can bind the MIR-222/221
      promoter, we hypothesized that MIR-222/221 represents the link between CBF and
      KIT. Here, we show that MIR-222/221 expression is upregulated after myeloid
      differentiation of normal bone marrow AC133(+) stem progenitor cells. CBFL blasts
      with either t(8;21) or inv(16) CBF rearrangements with high expression levels of
      KIT (CD117) display a significantly lower level of MIR-222/221 expression than
      non-CBFL blasts. Consistently, we found that the t(8;21) AML1-MTG8 fusion protein
      binds the MIR-222/221 promoter and induces transcriptional repression of a MIR
      222/221-LUC reporter. Because of the highly conserved sequence homology, we
      demonstrated concomitant MIR-222/221 down-regulation and KIT up-regulation in the
      32D/WT1 mouse cell model carrying the AML1-MTG16 fusion protein. This study
      provides the first hint that CBFL-associated fusion proteins may lead to up
      regulation of the KIT receptor by down-regulating MIR-222/221, thus explaining
      the concomitant occurrence of CBF genetic rearrangements and overexpression of
      wild type or mutant KIT in AML.

PMID- 21076614
TI  - Metastasis in melanoma xenografts is associated with tumor microvascular density
      rather than extent of hypoxia.
AB  - The development of metastases has been shown to be associated with the
      microvascular density of the primary tumor in some clinical studies and with the
      extent of hypoxia in others. The aim of this study was to investigate the
      validity of these apparently inconsistent observations and to reveal possible
      links between them. Xenografted tumors of nine melanoma cell lines established
      from patients with diseases differing in aggressiveness were studied. The
      aggressiveness of the cell lines was assessed by measuring their lung
      colonization potential, invasiveness, angiogenic potential, and tumorigenicity.
      Spontaneous metastasis was assessed in untreated mice and mice treated with
      neutralizing antibody against vascular endothelial growth factor A (VEGF-A) or
      interleukin 8 (IL-8). Microvascular density was scored in histologic
      preparations. Hypoxic fractions were measured by using a radiobiologic assay and
      a pimonidazole-based immunohistochemical assay. The aggressiveness of the
      melanoma lines reflected the aggressiveness of the donor patients' tumors. The
      metastatic propensity was associated with the microvascular density but not with
      the hypoxic fraction. Anti-VEGF-A and anti-IL-8 treatments resulted in decreased
      microvascular density and reduced incidence of metastases in all lines. Large
      hypoxic fractions were not a secondary effect of high cellular aggressiveness,
      whereas the microvascular density was associated with the cellular
      aggressiveness. The metastatic propensity was governed by the angiogenic
      potential of the tumor cells. The differences in microvascular density among the
      lines were most likely a consequence of differences in the constitutive
      angiogenic potential rather than differences in hypoxia-induced angiogenesis.
      VEGF-A and IL-8 may be important therapeutic targets for melanoma.

PMID- 21076616
TI  - RIG-I helicase-independent pathway in sendai virus-activated dendritic cells is
      critical for preventing lung metastasis of AT6.3 prostate cancer.
AB  - We recently demonstrated highly efficient antitumor immunity against dermal
      tumors of B16F10 murine melanoma with the use of dendritic cells (DCs) activated
      by replication-competent, as well as nontransmissible-type, recombinant Sendai
      viruses (rSeV), and proposed a new concept, "immunostimulatory virotherapy," for
      cancer immunotherapy. However, there has been little information on the
      efficacies of this method: 1) in more clinically relevant situations including
      metastatic diseases, 2) on other tumor types and other animal species, and 3) on
      the related molecular/cellular mechanisms. In this study, therefore, we
      investigated the efficacy of vaccinating DCs activated by fusion gene-deleted
      nontransmissible rSeV on a rat model of lung metastasis using a highly malignant
      subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent
      protein (GFP)-activated bone marrow-derived DCs (rSeV/dF-GFP-DC), consistent with
      results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was
      highly effective at preventing lung metastasis after intravenous loading of R
      3327 tumor cells, compared with the effects observed with immature DCs or
      lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC
      trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs
      expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I)
      (rSeV/dF-RIGIC-DC), an RNA helicase that recognizes the rSeV genome for inducing
      type I interferons, largely lost the expression of proinflammatory cytokines
      without any impairment of antitumor activity. These results indicate the
      essential role of RIG-I-independent signaling on antimetastatic effect induced by
      rSeV-activated DCs and may provide important insights to DC-based immunotherapy
      for advanced malignancies.

PMID- 21076617
TI  - Stromal activation associated with development of prostate cancer in prostate
      targeted fibroblast growth factor 8b transgenic mice.
AB  - Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in
      prostate cancer. Experimental studies have provided evidence that it plays a role
      in prostate tumorigenesis and tumor progression. To study how increased FGF-8
      affects the prostate, we generated and analyzed transgenic (TG) mice expressing
      FGF-8b under the probasin promoter that targets expression to prostate
      epithelium. Prostates of the TG mice showed an increased size and changes in
      stromal and epithelial morphology progressing from atypia and prostatic
      intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly
      variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and
      sarcoma. The development of mPIN lesions was preceded by formation of activated
      stroma containing increased proportion of fibroblastic cells, rich vasculature,
      and inflammation. The association between advancing stromal and epithelial
      alterations was statistically significant. Microarray analysis and validation
      with quantitative polymerase chain reaction revealed that expression of
      osteopontin and connective tissue growth factor was markedly upregulated in TG
      mouse prostates compared with wild type prostates. Androgen receptor staining was
      decreased in transformed epithelium and in hypercellular stroma but strongly
      increased in the sarcoma-like lesions. In conclusion, our data demonstrate that
      disruption of FGF signaling pathways by increased epithelial production of FGF-8b
      leads to strongly activated and atypical stroma, which precedes development of
      mPIN lesions and prostate cancer with mixed features of adenocarcinoma and
      sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in
      human prostate may also contribute to prostate tumorigenesis by stromal
      activation.

PMID- 21076618
TI  - Development of a resistance-like phenotype to sorafenib by human hepatocellular
      carcinoma cells is reversible and can be delayed by metronomic UFT chemotherapy.
AB  - Acquired resistance to antiangiogenic drugs, such as sorafenib, is a major
      clinical problem. We studied development of a resistance to sorafenib in new
      preclinical models of human hepatocellular carcinoma (HCC) along with a strategy
      to delay such resistance--combination with metronomic chemotherapy. Three
      different xenograft models were studied using human Hep3B HCC cells, which are
      highly responsive to sorafenib, namely, orthotopic and subcutaneous transplant in
      severe combined immunodeficient mice, and an orthotopic transplant in nude mice.
      The complementary DNA for the beta-subunit of human choriogonadotropin was
      transfected into HCC cells, and urine levels of the protein were monitored as a
      surrogate of tumor burden. Extended daily treatments, sometimes interrupted by a
      break period of 3 to 7 days to allow recovery from toxicity at sorafenib doses of
      30 to 60 mg/kg, were maintained until and after evidence of tumor relapse.
      Initially responsive tumors seemed to develop a resistance-like phenotype after
      long-term daily treatment (e.g., >42 days) at doses of 30 to 60 mg/kg.
      Transplantation of cell lines established from progressing tumors into new hosts
      showed that the resistant phenotype was not propagated. Furthermore, a regimen of
      daily metronomic uracil + tegafur (UFT, an oral 5-fluorouracil prodrug)
      chemotherapy with a less toxic regimen of sorafenib (15 mg/kg per day)
      significantly delayed the onset of resistance (>91 days). In conclusion,
      development of a resistance-like phenotype to sorafenib is reversible, and
      metronomic UFT plus sorafenib may be a promising and well-tolerated treatment for
      increasing efficacy by delaying emergence of such resistance.

PMID- 21076619
TI  - Phase 1/2 study of atrasentan combined with pegylated liposomal doxorubicin in
      platinum-resistant recurrent ovarian cancer.
AB  - BACKGROUND: Ovarian cancer overexpresses ET-1, and in vitro studies have shown
      that ET-1 confers resistance to anthracycline-containing chemotherapy. Atrasentan
      has been developed as an oral selective endothelin-A receptor antagonist. The
      objective of the study was to investigate the feasibility and toxicity of adding
      increasing doses of atrasentan (to a maximum of 10 mg/d) and liposomal
      doxorubicin in patients with progressive ovarian cancer, refractory for platinum
      and paclitaxel. METHODS: Patients with platinum-resistant ovarian cancer were
      treated with pegylated liposomal doxorubicin (PLD) 50 mg/m(2) on day 1 (and
      repeated every 4 weeks) in combination with escalating doses of atrasentan once
      daily. The starting dose was 2.5 mg and escalated in cohorts of three patients
      from 5 to 10 mg. RESULTS: Twenty-six patients (mean age = 60 years, range = 42-74
      years) were treated at the three dose levels. Atrasentan could be safely
      administered in combination at a dose of 10 mg. All patients were evaluable for
      toxicity, and 19 patients, included in the phase 2 period, were evaluable for
      response. Adverse events included nausea, vomiting, mucositis, skin toxicity, and
      rhinitis. Clinical cardiac toxicity, intensively monitored, was not observed,
      although two patients had a decrease in cardiac ejection fraction. Three
      objective responses were observed and another six patients had stable disease
      with a median time to progression of 14 weeks and an overall survival of 13.1
      months. CONCLUSIONS: The addition of atrasentan to standard dose PLD in platinum
      resistant ovarian cancer is feasible with some suggestion of prolonged survival.

PMID- 21076621
TI  - Chemical Treatments for Mobilizing Arsenic from Contaminated Aquifer Solids to
      Accelerate Remediation.
AB  - Arsenic is a prevalent contaminant at US Superfund sites where remediation by
      pump and treat systems is often complicated by slow desorption of As from Fe and
      Al (hydr)oxides in aquifer solids. Chemical amendments that either compete with
      As for sorption sites or dissolve Fe and Al (hydr)oxides can increase As mobility
      and improve pump and treat remediation efficiency. The goal of this work was to
      determine optimal amendments for improving pump and treat at As contaminated
      sites such as the Vineland Chemical Co. Superfund site in southern New Jersey.
      Extraction and column experiments were performed using As contaminated aquifer
      solids (81 +/- 1 mg/kg), site groundwater, and either phosphate
      (NaH(2)PO(4).H(2)O) or oxalic acid (C(2)H(2)O(4).2H(2)O). In extraction
      experiments, phosphate mobilized between 11% and 94% of As from the aquifer
      solids depending on phosphate concentration and extraction time (1 mM-1 M; 1-24
      h) and oxalic acid mobilized between 38 and 102% depending on oxalic acid
      concentration and extraction time (1-400 mM; 1-24 h). In column experiments,
      phosphate additions induced more As mobilization in the first few pore volumes
      but oxalic acid was more effective at mobilizing As overall and at lower
      amendment concentrations. At the end of the laboratory column experiments, 48% of
      As had been mobilized from the aquifer sediments with 100 mM phosphate and 88%
      had been mobilized with 10 mM oxalic acid compared with 5% with ambient
      groundwater alone. Furthermore, simple extrapolations based on pore volumes
      suggest that chemical treatments could lower the time necessary for clean up at
      the Vineland site from 600 a with ambient groundwater alone to potentially as
      little as 4 a with 10 mM oxalic acid.

PMID- 21076620
TI  - Induction of heparanase-1 expression by mutant B-Raf kinase: role of GA binding
      protein in heparanase-1 promoter activation.
AB  - Heparanase-1 (HPR1), an endoglycosidase that specifically degrades heparan
      sulfate (HS) proteoglycans, is overexpressed in a variety of malignancies. Our
      present study sought to determine whether oncogene BRAF and RAS mutations lead to
      increased HPR1 expression. Reverse transcription-polymerase chain reaction
      analysis revealed that HPR1 gene expression was increased in HEK293 cells
      transiently transfected with a mutant BRAF or RAS gene. Flow cytometric analysis
      revealed that B-Raf activation led to loss of the cell surface HS, which could be
      blocked by two HPR1 inhibitors: heparin and PI-88. Cotransfection of a BRAF or
      RAS mutant gene with HPR1 promoter-driven luciferase reporters increased
      luciferase reporter gene expression in HEK293 cells. Knockdown of BRAF expression
      in a BRAF-mutated KAT-10 tumor cell line led to the suppression of HPR1 gene
      expression, subsequently leading to increased cell surface HS levels.
      Truncational and mutational analyses of the HPR1 promoter revealed that the Ets
      relevant elements in the HPR1 promoter were critical for BRAF activation-induced
      HPR1 expression. Luciferase reporter gene expression driven by a four-copy GA
      binding protein (GABP) binding site was significantly lower in BRAF siRNA
      transfected KAT-10 cells than in the control siRNA-transfected cells. We further
      showed that BRAF knockdown led to suppression of the expression of the GABPbeta,
      an Ets family transcription factor involved in regulating HPR1 promoter activity.
      Taken together, our study suggests that B-Raf kinase activation plays an
      important role in regulating HPR1 expression. Increased HPR1 expression may
      contribute to the aggressive behavior of BRAF-mutated cancer.

PMID- 21076622
TI  - The role of interagency collaboration in facilitating receipt of behavioral
      health services for youth involved with child welfare and juvenile justice.
AB  - Unmet need for behavioral health care is a serious problem for crossover youth,
      or those simultaneously involved with the child welfare and juvenile justice
      systems. Although a large percentage of crossover youth are serious emotionally
      disturbed, relatively few receive necessary behavioral health services. Few
      studies have examined the role of interagency collaboration in facilitating
      behavioral health service access for crossover youth. This study examined
      associations for three dimensions of collaboration between local child welfare
      and juvenile justice agencies - jurisdiction, shared information systems, and
      overall connectivity - and youths' odds of receiving behavioral health services.
      Data were drawn from the National Survey of Child and Adolescent Well-Being, a
      national survey of families engaged with the child welfare system. Having a
      single agency accountable for youth care increased youth odds of receiving
      outpatient and inpatient behavioral health services. Inter-agency sharing of
      administrative data increased youth odds of inpatient behavioral health service
      receipt. Clarifying agency accountability and linking databases across sectors
      may improve service access for youth involved with both the child welfare and
      juvenile justice systems.

PMID- 21076623
TI  - Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl
      bromides with secondary phosphine oxides.
AB  - Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing
      aryl bromides with electron-deficient secondary phosphine oxides is reported. The
      resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX
      ligands. The presented strategy is a useful alternative to known methods for
      constructing PHOX derivatives.

PMID- 21076624
TI  - Phase Behavior and Vapor Pressures of the Pyrene + 9,10-Dibromoanthracene System.
AB  - The present work concerns the thermochemical and vapor pressure behavior of the
      pyrene + 9,10-dibromoanthracene system. The phase diagram of the system has been
      studied using the thaw melt method and the results show the formation of non
      eutectic multiphase mixtures. The temperatures of crystallization, and enthalpies
      of fusion and crystallization of the system were determined by differential
      scanning calorimetry. The system behavior can be divided into 5 regions. The X
      ray diffraction results also indicated the existence of multiple phase
      characteristics. The solid-vapor equilibrium studies showed that for mixtures
      with high mole fractions of pyrene, two different preferred states exist that
      determine the vapor pressure. For those mixtures with moderate and low mole
      fractions of pyrene, only one preferred state exists that determines vapor
      pressure behavior. It was also demonstrated that the vapor pressure of the
      mixtures is independent of the mixture preparation technique.

PMID- 21076625
TI  - Family Adaptability and Cohesion and High Blood Pressure among Urban African
      American women.
AB  - African American women are at greater risk for complications related to high
      blood pressure. This study examined relationships between high blood pressure,
      pulse pressure, body mass index, family adaptability, family cohesion and social
      support among 146 Urban African American women. Significant relationships were
      found between family adaptability and systolic blood pressure (p = .03) and
      between adaptability and pulse pressure (p <= .01). Based on study results,
      practitioners should routinely assess family functioning, specifically family
      adaptability, in African American women who are at risk for high blood pressure
      or diagnosed with high blood pressure to minimize complications associated with
      hypertension.

PMID- 21076626
TI  - Ectopic expression of rice Xa21 overcomes developmentally controlled resistance
      to Xanthomonas oryzae pv. oryzae.
AB  - Recognition of pathogen-associated molecular patterns (PAMPs) by pattern
      recognition receptors (PRRs) activates the innate immune response. The rice PRR,
      XA21, confers robust resistance at adult stages to most strains of the bacterial
      pathogen Xanthomonas oryzae pv. oryzae (Xoo). Seedlings are still easily infected
      by Xoo, causing severe yield losses. Here we report that Xa21 is induced by Xoo
      infection and that ectopic expression of Xa21 confers resistance at three leaf
      stage (three-week-old), overcoming the developmental limitation of XA21-mediated
      resistance. Ectopic expression of Xa21 also up-regulates a larger set of defense
      related genes as compared to Xa21 driven by the native promoter. These results
      indicate that altered regulation of Xa21 expression is useful for developing
      enhanced resistance to Xoo at multiple developmental stages.

PMID- 21076627
TI  - Solution of a Complex Least Squares Problem with Constrained Phase.
AB  - The least squares solution of a complex linear equation is in general a complex
      vector with independent real and imaginary parts. In certain applications in
      magnetic resonance imaging, a solution is desired such that each element has the
      same phase. A direct method for obtaining the least squares solution to the phase
      constrained problem is described.

PMID- 21076628
TI  - Oxidative degradation of reducing carbohydrates to ammonium formate with H(2)O(2)
      and NH(4)OH.
AB  - Oxidation of various carbohydrates to ammonium formate was investigated in the
      presence of hydrogen peroxide and ammonium hydroxide. Most of the examined
      carbohydrates except nonreducing sugars were efficiently converted into ammonium
      formate under environment friendly and mild conditions in aqueous media.

PMID- 21076629
TI  - Effects of event knowledge in processing verbal arguments.
AB  - This research tests whether comprehenders use their knowledge of typical events
      in real time to process verbal arguments. In self-paced reading and event-related
      brain potential (ERP) experiments, we used materials in which the likelihood of a
      specific patient noun (brakes or spelling) depended on the combination of an
      agent and verb (mechanic checked vs. journalist checked). Reading times were
      shorter at the word directly following the patient for the congruent than the
      incongruent items. Differential N400s were found earlier, immediately at the
      patient. Norming studies ruled out any account of these results based on direct
      relations between the agent and patient. Thus, comprehenders dynamically combine
      information about real-world events based on intrasentential agents and verbs,
      and this combination then rapidly influences online sentence interpretation.

PMID- 21076630
TI  - Achieving lipid targets in adults with type 2 diabetes: the Stop Atherosclerosis
      in Native Diabetics Study.
AB  - BACKGROUND: Although lipid management in diabetes is standard practice, goals
      often are neither met nor maintained. Strategies for achieving lower targets have
      not been explored. The Stop Atherosclerosis in Native Diabetics Study randomized
      patients with diabetes to standard versus aggressive lipid and blood pressure
      goals for 36 months. OBJECTIVE: To report strategies used to achieve and maintain
      lipid goals and to report adverse events (AEs). METHODS: Adults with type 2
      diabetes and no history of cardiovascular disease (N = 499) were randomized to
      standard (low-density lipoprotein cholesterol [LDL-C] <= 100 mg/dL, non-high
      density lipoprotein cholesterol [non-HDL-C] <= 130 mg/dL) or aggressive (LDL-C <=
      70 mg/dL, non-HDL-C <= 100 mg/dL) targets. An algorithm was started with statin
      monotherapy, with intestinally acting agents added as required to reach LDL-C
      targets.Triglyceride [TG]-lowering agents were next used to reach non-HDL-C
      goals. Lipid management was performed by mid-level practitioners, with physician
      consultation, by the use of point-of-care lipid determinations. RESULTS: On
      average, both groups achieved the LDL-C and non-HDL-C goals within 12 months and
      maintained them throughout the study. At 36 months, mean (SD) LDL-C and non-HDL-C
      were 72 (24) and 102 (29) mg/dL in the aggressive group (AGG) and 104 (20) and
      138 (26) mg/dL, respectively, in the standard group (STD); systolic blood
      pressure targets were 115 and 130 mmHg, respectively. A total of 68% of
      participants reached target LDL-C for greater than 50% of the visits and 46% for
      greater than 75% of visits. At 36 months, the AGG averaged 1.5 lipid lowering
      medications and the STD 1.2. Statins were used in 91% and 68% of the AGG and STD;
      ezetimibe by 31% and 10%; fibrates by 8% and 18%. No serious AEs were observed;
      AEs occurred in 18% of the AGG and 14% of the STD. CONCLUSION: Standard and
      aggressive lipid targets can be safely maintained in diabetic patients.
      Standardized algorithms, point-of-care lipid testing, and nonphysician providers
      facilitate care delivery.

PMID- 21076631
TI  - Functions of cholesterol ester transfer protein and relationship to coronary
      artery disease risk.

PMID- 21076632
TI  - Airflow and nanoparticle deposition in rat nose under various breathing and
      sniffing conditions: a computational evaluation of the unsteady effect.
AB  - Accurate prediction of nanoparticle (1~100 nm) deposition in the rat nasal cavity
      is important for assessing the toxicological impact of inhaled nanoparticles as
      well as for potential therapeutic applications. A quasi-steady assumption has
      been widely adopted in the past investigations on this topic, yet the validity of
      such simplification under various breathing and sniffing conditions has not been
      carefully examined. In this study, both steady and unsteady computational fluid
      dynamics (CFD) simulations were conducted in a published rat nasal model under
      various physiologically realistic breathing and sniffing flow rates. The
      transient airflow structures, nanoparticle transport and deposition patterns in
      the whole nasal cavity and the olfactory region were investigated and compared
      with steady state simulation of equivalent flow rate. The results showed that (1)
      the quasi-steady flow assumption for cyclic flow was valid for over 70% of the
      cycle period during all simulated breathing and sniffing conditions in the rat
      nasal cavity, or the unsteady effect was only significant during the transition
      between the respiratory phases; (2) yet the quasi-steady assumption for
      nanoparticle transport was not valid, except in the vicinity of peak respiration.
      In general, the total deposition efficiency of nanoparticle during cyclic
      breathing would be lower than that of steady state due to the unsteady effect on
      particle transport and deposition, and further decreased with the increase of
      particle size, sniffing frequency, and flow rate. In the contrary, previous study
      indicated that for micro-scale particles (0.5~4MUm), the unsteady effect would
      increase deposition efficiencies in rat nasal cavity. Combined, these results
      suggest that the quasi-steady assumption of nasal particle transport during
      cycling breathing should be used with caution for an accurate assessment of the
      toxicological and therapeutic impact of particle inhalation. Empirical equations
      and effective steady state approximation derived in this study are thus valuable
      to estimate such unsteady effects in future applications.

PMID- 21076633
TI  - Myeloperoxidase, inflammation, and dysfunctional high-density lipoprotein.
AB  - High-density lipoprotein (HDL) has many protective activities against
      atherosclerosis, including its role in reverse cholesterol transport, and its
      antioxidant, anti-inflammatory, and endothelial cell maintenance functions.
      However, all HDL is not functionally equivalent. The authors of recent studies
      have shown that infection, inflammation, diabetes, and coronary artery disease
      are associated with dysfunctional HDL. HDL can lose its protective activities
      through a variety of mechanisms, including, but not limited to, altered protein
      composition, oxidative protein modification mediated by the enzyme
      myeloperoxidase, and lipid modification. Studies in which the authors used
      bacterial endotoxin in humans and mice have directly demonstrated changes in HDL
      composition, loss of HDL's cholesterol acceptor activity, and decreased hepatic
      processing and secretion of cholesterol. Although a routine clinical assay for
      dysfunctional HDL is not currently available, the development of such an assay
      would be beneficial for a better understanding of the role that dysfunctional HDL
      plays as a risk factor for coronary artery disease and for the determination of
      how various drug therapies effect HDL functionality.

PMID- 21076634
TI  - Coping with Daily Stress: The Role of Conscientiousness.
AB  - The current study examined how specific coping strategies mediate the
      relationship between Conscientiousness (C) and positive affect (PA) in a large,
      multiethnic sample. Using an internet-based daily diary approach, 366
      participants (37.6% Caucasian, 30.6% Asian American, 20.7% Hispanic, 9.1% African
      American) completed measures that assessed daily stressors, coping strategies
      used to deal with those stressors, and PA over the course of five days. In
      addition, participants completed a measure of the Five-Factor Model of
      Personality. Problem-Focused coping partially mediated the relationship between C
      and PA. Individuals higher in C used more problem-focused coping, which, in turn,
      was associated with higher PA. The findings of the current study suggest C serves
      as a protective factor from stress through its influence on coping strategy
      selection. Other possible mediators in the C-PA relationship are discussed.

PMID- 21076635
TI  - Chemical synthesis of deuterium-labeled and unlabeled very long chain
      polyunsaturated fatty acids.
AB  - First syntheses of a deuterium-labeled very long C34-containing polyunsaturated
      fatty acid, C34:5n5.d(2), and three other unlabeled very long chain C30-32
      containing polyunsaturated fatty acids are reported here. These syntheses were
      achieved by coupling chemically modified C22- and C20-containing polyunsaturated
      fatty acids with carbanions derived from arylalkyl sulfones, followed by sodium
      amalgam-mediated desulfonylation.

PMID- 21076636
TI  - Modeling effects of traffic and landscape characteristics on ambient nitrogen
      dioxide levels in Connecticut.
AB  - An integrated exposure model was developed that estimates nitrogen dioxide
      (NO(2)) concentration at residences using geographic information systems (GIS)
      and variables derived within residential buffers representing traffic volume and
      landscape characteristics including land use, population density and elevation.
      Multiple measurements of NO(2) taken outside of 985 residences in Connecticut
      were used to develop the model. A second set of 120 outdoor NO(2) measurements as
      well as cross-validation were used to validate the model. The model suggests that
      approximately 67% of the variation in NO(2) levels can be explained by: traffic
      and land use primarily within 2 km of a residence; population density; elevation;
      and time of year. Potential benefits of this model for health effects research
      include improved spatial estimations of traffic-related pollutant exposure and
      reduced need for extensive pollutant measurements. The model, which could be
      calibrated and applied in areas other than Connecticut, has importance as a tool
      for exposure estimation in epidemiological studies of traffic-related air
      pollution.

PMID- 21076637
TI  - Synthesis of a Tricyclic Core of Rameswaralide.
AB  - A tricyclic core containing a 5,7-fused bicyclic unit of rameswaralide was
      prepared starting from a 1,6-enyne. The synthetic sequence involved (i) ruthenium
      catalyzed [5+2]-cycloaddition of 1,6-enyne, (ii) an acyl radical based approach
      to construct the lactone, and (iii) a regioselective installation of the
      conjugated double bond by a concomitant sulfenylation-dehydrosulfenylation
      sequence.

PMID- 21076638
TI  - Influence of Matrices on Oxygen Sensing of Three Sensing Films with Chemically
      Conjugated Platinum Porphyrin Probes and Preliminary Application for Monitoring
      of Oxygen Consumption of Escherichia coli (E. coli).
AB  - Oxygen sensing films were synthesized by a chemical conjugation of functional
      platinum porphyrin probes in silica gel, polystyrene (PS), and poly(2
      hydroxyethyl methacrylate) (PHEMA) matrices. Responses of the sensing films to
      gaseous oxygen and dissolved oxygen were studied and the influence of the
      matrices on the sensing behaviors was investigated. Silica gel films had the
      highest fluorescence intensity ratio from deoxygenated to oxygenated environments
      and the fastest response time to oxygen. PHEMA films had no response to gaseous
      oxygen, but had greater sensitivity and a faster response time for dissolved
      oxygen than those of PS films. The influence of matrices on oxygen response,
      sensitivity and response time was discussed. The influence is most likely
      attributed to the oxygen diffusion abilities of the matrices. Since the probes
      were chemically immobilized in the matrices, no leaching of the probes was
      observed from the sensing films when applied in aqueous environment. One sensing
      film made from the PHEMA matrix was used to preliminarily monitor the oxygen
      consumption of Escherichia coli (E. coli) bacteria. E. coli cell density and
      antibiotics ampicillin concentration dependent oxygen consumption was observed,
      indicating the potential application of the oxygen sensing film for biological
      application.

PMID- 21076639
TI  - Marine isolates of Aspergillus flavus: denizens of the deep or lost at sea?
AB  - Most fungal species from marine environments also live on land. It is not clear
      whether these fungi reach the sea from terrestrial sources as spores or other
      propagules, or if there are separate ecotypes that live and reproduce in the sea.
      The emergence of marine diseases has created an urgency to understand the
      distribution of these fungi. Aspergillus flavus is ubiquitous in both terrestrial
      and marine environments. This species is an opportunistic pathogen in many hosts,
      making it a good model to study the relationship between genetic diversity and
      specificity of marine fungi. In this study, an intraspecific phylogeny of A.
      flavus isolates based on Amplified Fragment Length Polymorphisms (AFLPs) was used
      to determine if terrestrial and marine isolates form discrete populations, and to
      determine if phylogeny predicts substratum specificity. Results suggest lack of
      population structure in A. flavus. All isolates may compose a single population,
      with no clade particular to marine environments.

PMID- 21076641
TI  - MOLECULAR MARKERS OF EARLY CERVICAL NEOPLASIA.
AB  - Pure morphological distinction of high-grade squamous intraepithelial lesions
      (HSILs) from their mimics can be challenging. Diagnosis can be difficult with
      nonconventional HSILs associated with a metaplastic phenotype, squamous
      intraepithelial lesions (SILs) that defy precise classification such as
      "eosinophilic dysplasias", and those that overlap with columnar neoplasms,
      including stratified variants of adenocarcinoma in situ ("SMILE"). Gene
      expression and protein profiling have identified biomarkers with the potential to
      decrease diagnostic variability and increase specificity of histological and
      cytological analysis. Among the ones clinically useful for HSIL detection are
      p16(INK4A) and MIB-1 which complement each other, differentiating SIL from
      normal/atrophic (MIB-1 low) or reactive/immature metaplastic (p16(INK4A)
      scattered) epithelium. Additional markers, including ProEx(TM) C, have been
      proposed but their added value is yet to be established. In the final analysis,
      biomarkers are most helpful for distinguishing benign immature or atrophic
      proliferations from HSIL. The distinction of LSIL from HSIL must be made on the
      hematoxylin and eosin-stained section and should be made with care, given the
      potential consequences of a diagnosis of CIN2 or CIN3.

PMID- 21076640
TI  - Does M. tuberculosis genomic diversity explain disease diversity?
AB  - The outcome of tuberculosis infection and disease is highly variable. This
      variation has been attributed primarily to host and environmental factors, but
      better understanding of the global genomic diversity in the M. tuberculosis
      complex (MTBC) suggests that bacterial factors could also be involved. Review of
      nearly 100 published reports shows that MTBC strains differ in their virulence
      and immunogenicity in experimental models, but whether this phenotypic variation
      plays a role in human disease remains unclear. Given the complex interactions
      between the host, the pathogen and the environment, linking MTBC genotypic
      diversity to experimental and clinical phenotypes requires an integrated systems
      epidemiology approach embedded in a robust evolutionary framework.

PMID- 21076643
TI  - QM/MM Studies of the Matrix Metalloproteinase 2 (MMP2) Inhibition Mechanism of
      (S)-SB-3CT and its Oxirane Analogue.
AB  - SB-3CT, (4-phenoxyphenylsulfonyl)methylthiirane, is a potent, mechanism-based
      inhibitor of the gelatinase sub-class of the matrix metalloproteinase (MMP)
      family of zinc proteases. The gelatinase MMPs are unusual in that there are
      several examples where both enantiomers of a racemic inhibitor have comparable
      inhibitory abilities. SB-3CT is one such example. Here, the inhibition mechanism
      of the MMP2 gelatinase by the (S)-SB-3CT enantiomer and its oxirane analogue is
      examined computationally, and compared to the mechanism of (R)-SB-3CT. Inhibition
      of MMP2 by (R)-SB-3CT was shown previously to involve enzyme-catalyzed C-H
      deprotonation adjacent to the sulfone, with concomitant opening by beta
      elimination of the sulfur of the three-membered thiirane ring. Similarly to the R
      enantiomer, (S)-SB-3CT was docked into the active site of MMP2, followed by
      molecular dynamics simulation to prepare the complex for combined quantum
      mechanics and molecular mechanics (QM/MM) calculations. QM/MM calculations with
      B3LYP/6-311+G(d,p) for the QM part (46 atoms) and the AMBER force field for the
      MM part were used to compare the reaction of (S)-SB-3CT and its oxirane analogue
      in the active site of MMP2 (9208 atoms). These calculations show that the barrier
      for the proton abstraction coupled ring opening reaction of (S)-SB-3CT in the
      MMP2 active site is 4.4 kcal/mol lower than its oxirane analogue, and the ring
      opening reaction energy of (S)-SB-3CT is only 1.6 kcal/mol less exothermic than
      its oxirane analogue. Calculations also show that the protonation of the ring
      opened products by water is thermodynamically much more favorable for the
      alkoxide obtained from the oxirane, than for the thiolate obtained from the
      thiirane. In contrast to (R)-SB-3CT and the R-oxirane analogue, the double bonds
      of the ring-opened products of (S)-SB-3CT and its S-oxirane analogue have the cis
      configuration. Vibrational frequency and intrinsic reaction path calculations on
      a reduced size QM/MM model (2747 atoms) provide additional insight into the
      mechanism. These calculations yield 5.9 and 6.7 for the deuterium kinetic isotope
      effect for C-H bond cleavage in the transition state for the R and S enantiomers
      of SB-3CT, in good agreement with the experimental results.

PMID- 21076642
TI  - Structural and functional parameters of the flaviviral protease: a promising
      antiviral drug target.
AB  - Flaviviruses have a single-strand, positive-polarity RNA genome that encodes a
      single polyprotein. The polyprotein is comprised of seven nonstructural (NS) and
      three structural proteins. The N- and C-terminal parts of NS3 represent the
      serine protease and the RNA helicase, respectively. The cleavage of the
      polyprotein by the protease is required to produce the individual viral proteins,
      which assemble a new viral progeny. Conversely, inactivation of the protease
      blocks viral infection. Both the protease and the helicase are conserved among
      flaviviruses. As a result, NS3 is a promising drug target in flaviviral
      infections. This article examines the West Nile virus NS3 with an emphasis on the
      structural and functional parameters of the protease, the helicase and their
      cofactors.

PMID- 21076645
TI  - The Uniformity and Diversity of Language: Evidence from Sign Language.
AB  - Evidence from sign language strongly supports three positions: (1) language is a
      coherent system with universal properties; (2) sign languages diverge from spoken
      languages in some aspects of their structure; and (3) domain-external factors can
      be identified that account for some crucial aspects of language structure --
      uniform and diverse -- in both modalities. Assuming that any of these positions
      excludes the others defeats the purpose of the enterprise.

PMID- 21076644
TI  - Quantification of Lacunar-Canalicular Interstitial Fluid Flow Through
      Computational Modeling of Fluorescence Recovery After Photobleaching.
AB  - Skeletal adaptation to mechanical loading has been widely hypothesized to involve
      the stimulation of osteocytes by interstitial fluid flow (IFF). However, direct
      investigation of this hypothesis has been difficult due in large part to the
      inability to directly measure IFF velocities within the lacunar-canalicular
      system. Measurements of fluorescence recovery after photobleaching (FRAP) within
      individual lacunae could be used to quantify lacunar-canalicular IFF when
      combined with mathematical modeling. In this study, we used a computational
      transport model to characterize the relationship between flow frequency (0.5-10
      Hz), peak flow velocity (0-300 MUm/s), tracer diffusion coefficient (100-300
      MUm(2)/s), and transport enhancement (i.e., (k/k(0)) - 1, where k and k(0) are
      the transport rates in the presence/absence of flow) during lacunar FRAP
      investigations. We show that this relationship is well described by a simple
      power law with frequency-dependent coefficients, and is relatively insensitive to
      variations in lacunar geometry. Using this power law relationship, we estimated
      peak IFF velocities in hindlimb mice subjected to intramedullary pressurization
      using values of k and k(0) previously obtained from ex vivo lacunar FRAP
      investigations. Together, our findings suggest that skeletal adaptation in
      hindlimb suspended mice subjected to dynamic intramedullary pressure occurred in
      the presence of IFF at levels associated with physiological loading.

PMID- 21076646
TI  - Assets and Educational Outcomes: Child Development Accounts (CDAs) for Orphaned
      Children in Uganda.

PMID- 21076647
TI  - Personal genomics and individual identities: motivations and moral imperatives of
      early users.
AB  - Since 2007, consumer genomics companies have marketed personal genome scanning
      services to assess users' genetic predispositions to a variety of complex
      diseases and traits. This study investigates early users' reasons for utilizing
      personal genome services, their evaluation of the technology, how they interpret
      the results, and how they incorporate the results into health-related decision
      making. The analysis contextualizes early users' relationships to the technology,
      the knowledge generated by it, and how it mediates their relationship to their
      own health and to biomedicine more broadly. The results reveal that early users
      approach personal genome scanning with both optimism for genomic research and
      scepticism about the technology's current capabilities, which runs contrary to
      concerns that consumers may be ill equipped to interpret and understand genome
      scan results. These findings provide important qualitative insight into early
      users' conceptualizations of personal genomic risk assessment and illuminate
      their involvement in configuring this technology in the making.

PMID- 21076649
TI  - Indium-mediated allylation of aldehydes, ketones and sulfonimines with 2
      (alkoxy)allyl bromides.
AB  - 2-(Alkoxy)propenyl bromides are readily prepared from 1,3-dibromo-2-propanol in a
      two-step sequence involving hydroxyl protection and sodium hydride-induced
      dehydrobromination. Indium-mediated allylation of aldehydes, ketones, and
      sulfonimines with 2-(alkoxy)propenyl bromides furnishes the corresponding
      homoallylic alcohols and sulfonamines in good yields. The products can be easily
      transformed into beta-hydroxy ketones and esters, as well as substituted
      dihydropyrans and protected beta-amino acids. Chiral 2-(alkoxy)propenyl halides,
      derived from (-)-menthol and D-glucal, furnish diastereomerically enriched
      products.

PMID- 21076648
TI  - Real-time processing of gender-marked articles by native and non-native Spanish
      speakers.
AB  - Three experiments using online processing measures explored whether native and
      non-native Spanish-speaking adults use gender-marked articles to identify
      referents of target nouns more rapidly, as shown previously with 3-year-old
      children learning Spanish as L1 (Lew-Williams & Fernald, 2007). In Experiment 1,
      participants viewed familiar objects with names of either the same or different
      grammatical gender while listening to Spanish sentences referring to one object.
      L1 adults, like L1 children, oriented to the target more rapidly on different
      gender trials, when the article was informative about noun identity; however, L2
      adults did not. Experiments 2 and 3 controlled for frequency of exposure to
      article-noun pairs by using novel nouns. L2 adults could not exploit gender
      information when different article-noun pairs were used in teaching and testing.
      Experience-related factors may influence how L1 adults and children and L2 adults
      who learned Spanish at different ages and in different settings-use grammatical
      gender in realtime processing.

PMID- 21076650
TI  - FEATURE-BASED MULTIBLOCK FINITE ELEMENT MESH GENERATION.
AB  - Hexahedral finite element mesh development for anatomic structures and biomedical
      implants can be cumbersome. Moreover, using traditional meshing techniques,
      detailed features may be inadequately captured. In this paper, we describe
      methodologies to handle multi-feature datasets (i.e., feature edges and
      surfaces). Coupling multi-feature information with multiblock meshing techniques
      has enabled anatomic structures, as well as orthopaedic implants, to be readily
      meshed. Moreover, the projection process, node and element set creation are
      automated, thus reducing the user interaction during model development. To
      improve the mesh quality, Laplacian- and optimization-based mesh improvement
      algorithms have been adapted to the multi-feature datasets.

PMID- 21076651
TI  - THE IMPACT OF FALLIBLE ITEM PARAMETER ESTIMATES ON LATENT TRAIT RECOVERY.
AB  - In this paper we propose an upward correction to the standard error (SE)
      estimation of theta(ML), the maximum likelihood (ML) estimate of the latent trait
      in item response theory (IRT). More specifically, the upward correction is
      provided for the SE of theta(ML) when item parameter estimates obtained from an
      independent pretest sample are used in IRT scoring. When item parameter estimates
      are employed, the resulting latent trait estimate is called pseudo maximum
      likelihood (PML) estimate. Traditionally the SE of theta(ML) is obtained on the
      basis of test information only, as if the item parameters are known. The upward
      correction takes into account the error that is carried over from the estimation
      of item parameters, in addition to the error in latent trait recovery itself. Our
      simulation study shows that both types of SE estimates are very good when theta
      is in the middle range of the latent trait distribution, but the upward-corrected
      SEs are more accurate than the traditional ones when theta takes more extreme
      values.

PMID- 21076652
TI  - A semi-parametric generalization of the Cox proportional hazards regression
      model: Inference and Applications.
AB  - The assumption of proportional hazards (PH) fundamental to the Cox PH model
      sometimes may not hold in practice. In this paper, we propose a generalization of
      the Cox PH model in terms of the cumulative hazard function taking a form similar
      to the Cox PH model, with the extension that the baseline cumulative hazard
      function is raised to a power function. Our model allows for interaction between
      covariates and the baseline hazard and it also includes, for the two sample
      problem, the case of two Weibull distributions and two extreme value
      distributions differing in both scale and shape parameters. The partial
      likelihood approach can not be applied here to estimate the model parameters. We
      use the full likelihood approach via a cubic B-spline approximation for the
      baseline hazard to estimate the model parameters. A semi-automatic procedure for
      knot selection based on Akaike's Information Criterion is developed. We
      illustrate the applicability of our approach using real-life data.

PMID- 21076653
TI  - Narcissism Predicts Heightened Cortisol Reactivity to a Psychosocial Stressor in
      Men.
AB  - Narcissists' sensitivity to social evaluation should increase their physiological
      reactivity to evaluative stressors. However, very few studies have assessed the
      physiological correlates of narcissism. In this study, participants completed an
      evaluative laboratory stressor or a non-evaluative control task. Cortisol
      reactivity-a marker of the hypothalamic-pituitary-adrenal (HPA) axis stress
      response-and negative affect (NA) were higher in the stress versus control
      condition. However, men showed larger cortisol responses and, among men, higher
      narcissism scores predicted greater cortisol reactivity and larger increases in
      NA. Narcissism was unrelated to cortisol reactivity and NA among women and in the
      control condition. These findings highlight the influence of defensive
      personality traits on HPA reactivity and suggest a pathway through which
      narcissistic traits might influence long-term health outcomes.

PMID- 21076654
TI  - New Approaches to Nutritional Therapy.

PMID- 21076655
TI  - N-Nosyl Oxaziridines as Terminal Oxidants in Copper(II)-Catalyzed Olefin
      Oxyaminations.
AB  - We report that N-4-nosyl-3-phenyloxaziridine is an effective terminal oxidant for
      copper(II)-catalyzed oxyamination recently developed in our labs. This
      oxaziridine can be prepared on multi-gram scale and is easily purified by
      recrystallization. The products of oxyamination using this oxaziridine bear
      protecting groups that can be readily removed in high yields under mild
      conditions.

PMID- 21076657
TI  - The Role of Maternal Verbal, Affective, and Behavioral Support in Preschool
      Children's Independent and Collaborative Autobiographical Memory Reports.
AB  - The authors investigated the individual and relative contributions of different
      aspects of maternal support (i.e., verbal, affective, and behavioral) in relation
      to children's collaborative and independent reminiscing. Four-year-old children
      discussed personal past experiences with their mothers and with a researcher. In
      collaborative recall with their mothers, children's narrative behavior was
      regulated best by maternal use of specific elaborative components, such as
      affirmations. In contrast, in children's independent recall, affective and
      behavioral qualities of maternal support were related to children's memory
      performance. Specifically, during free-recall, the dimensions of quality of
      instruction and respect for autonomy were significant predictors of children's
      narratives. In the context of prompted recall (supported by wh-questions),
      respect for autonomy was the only significant predictor of children's involvement
      in the conversations and of the amount of unique content they provided. The
      findings suggest that different aspects of maternal behavior facilitate different
      components of children's reminiscing skills, which children might apply depending
      on demands of the autobiographical memory conversation.

PMID- 21076658
TI  - A Fast Procedure for Calculating Importance Weights in Bootstrap Sampling.
AB  - Importance sampling is an efficient strategy for reducing the variance of certain
      bootstrap estimates. It has found wide applications in bootstrap quantile
      estimation, proportional hazards regression, bootstrap confidence interval
      estimation, and other problems. Although estimation of the optimal sampling
      weights is a special case of convex programming, generic optimization methods are
      frustratingly slow on problems with large numbers of observations. For instance,
      interior point and adaptive barrier methods must cope with forming, storing, and
      inverting the Hessian of the objective function. In this paper, we present an
      efficient procedure for calculating the optimal importance weights and compare
      its performance to standard optimization methods on a representative data set.
      The procedure combines several potent ideas for large scale optimization.

PMID- 21076656
TI  - Size Does Matter: Application-driven Approaches for Soil Metagenomics.
AB  - Metagenomic analyses can provide extensive information on the structure,
      composition, and predicted gene functions of diverse environmental microbial
      assemblages. Each environment presents its own unique challenges to metagenomic
      investigation and requires a specifically designed approach to accommodate
      physicochemical and biotic factors unique to each environment that can pose
      technical hurdles and/or bias the metagenomic analyses. In particular, soils
      harbor an exceptional diversity of prokaryotes that are largely undescribed
      beyond the level of ribotype and are a potentially vast resource for natural
      product discovery. The successful application of a soil metagenomic approach
      depends on selecting the appropriate DNA extraction, purification, and if
      necessary, cloning methods for the intended downstream analyses. The most
      important technical considerations in a metagenomic study include obtaining a
      sufficient yield of high-purity DNA representing the targeted microorganisms
      within an environmental sample or enrichment and (if required) constructing a
      metagenomic library in a suitable vector and host. Size does matter in the
      context of the average insert size within a clone library or the sequence read
      length for a high-throughput sequencing approach. It is also imperative to select
      the appropriate metagenomic screening strategy to address the specific
      question(s) of interest, which should drive the selection of methods used in the
      earlier stages of a metagenomic project (e.g., DNA size, to clone or not to
      clone). Here, we present both the promising and problematic nature of soil
      metagenomics and discuss the factors that should be considered when selecting
      soil sampling, DNA extraction, purification, and cloning methods to implement
      based on the ultimate study objectives.

PMID- 21076659
TI  - Impact of Empowerment Training on the Professional Work of Family Peer Advocates.
AB  - A pilot study using a prospective design examined the impact of a collaboratively
      developed training model, called the Parent Empowerment Program (PEP), for
      professionally-employed family peer advocates who work with caregivers of
      children with mental health needs. This training used a combination of didactic,
      practice exercises, and group discussion. It targeted specific mental health
      knowledge content and collaborative skills to facilitate the work of family peer
      advocates in empowering caregivers. Co-delivered by a family peer advocate and
      clinician, the training consisted of a 40-hour face-to-face training, followed by
      six monthly face-to-face booster sessions. A total of 15 advocates participated
      in assessments conducted at baseline and post-training. This group of experienced
      family peer advocates showed no significant increase in knowledge about mental
      health content, but post-training assessments indicated increased collaborative
      skills and mental health services self-efficacy. This initial evaluation has
      implications for expanding training and support for the emergent workforce of
      professionally-employed family peer advocates in children's mental health.

PMID- 21076660
TI  - When is peer rejection justifiable?: Children's understanding across two
      cultures.
AB  - This study investigated how Korean (N = 397) and U.S. (N = 333) children and
      adolescents (10 and 13 years of age) evaluated personality (aggression, shyness)
      and group (gender, nationality) characteristics as a basis for peer rejection in
      three contexts (friendship rejection, group exclusion, victimization). Overall,
      peer rejection based on group membership was viewed as more unfair than peer
      rejection based on personality traits. Children viewed friendship rejection as
      more legitimate than group exclusion or victimization and used more personal
      choice reasoning for friendship rejection than for rejection in any other
      context. Although there were a few cultural differences, overall, the findings
      provided support for the cultural generalizability of social reasoning about peer
      rejection.

PMID- 21076661
TI  - Naming and repetition in aphasia: Steps, routes, and frequency effects.
AB  - This paper investigates the cognitive processes underlying picture naming and
      auditory word repetition. In the 2-step model of lexical access, both the
      semantic and phonological steps are involved in naming, but the former has no
      role in repetition. Assuming recognition of the to-be-repeated word, repetition
      could consist of retrieving the word's output phonemes from the lexicon (the
      lexical-route model), retrieving the output phonology directly from input
      phonology (the nonlexical-route model) or employing both routes together (the
      summation dual-route model). We tested these accounts by comparing the size of
      the word frequency effect (an index of lexical retrieval) in naming and
      repetition data from 59 aphasic patients with simulations of naming and
      repetition models. The magnitude of the frequency effect (and the influence of
      other lexical variables) was found to be comparable in naming and repetition, and
      equally large for both the lexical and summation dual-route models. However, only
      the dual-route model was fully consistent with data from patients, suggesting
      that nonlexical input is added on top of a fully-utilized lexical route.

PMID- 21076662
TI  - Talking about Internal States in Mother-Child Reminiscing Influences Children's
      Self-Representations: A Cross-Cultural Study.
AB  - This study examined the relation of mother-child discussions of internal states
      during reminiscing to the development of trait and evaluative self
      representations in 131 European American and Chinese immigrant 3-year-olds.
      Mothers and children discussed one positive and one negative event, and children
      were interviewed for self-descriptions. Euro-American mothers and children made
      more references to internal states and focused more on causal talk than did
      Chinese, and Euro-American children were more likely than Chinese children to
      describe their own traits and evaluative characteristics. Mothers' and children's
      use of internal state language during reminiscing of the negative event uniquely
      predicted children's trait and evaluative self-representations, independent of
      culture. Explanations of internal states and conversing in the negative event
      context were particularly effective in predicting children's self
      representations. Discussions of internal states further mediated cultural
      influences on children's self-representations. The findings provide new insight
      into the contribution of parent-child reminiscing to the development of self.

PMID- 21076664
TI  - Edge-Functionalization of Pyrene as a Miniature Graphene via Friedel-Crafts
      Acylation Reaction in Poly(Phosphoric Acid).
AB  - The feasibility of edge-functionalization of graphite was tested via the model
      reaction between pyrene and 4-(2,4,6-trimethylphenyloxy)benzamide (TMPBA) in
      poly(phosphoric acid) (PPA)/phosphorous pentoxide (P(2)O(5)) medium. The
      functionalization was confirmed by various characterization techniques. On the
      basis of the model study, the reaction condition could be extended to the edge
      functionalization of graphite with TMPBA. Preliminary results showed that the
      resultant TMPBA-grafted graphite (graphite-g-TMPBA) was found to be readily
      dispersible in N-methyl-2-pyrrolidone (NMP) and can be used as a precursor for
      edge-functionalized graphene (EFG). 

PMID- 21076663
TI  - An Adaptive Multigrid Algorithm for Simulating Solid Tumor Growth Using Mixture
      Models.
AB  - In this paper we give the details of the numerical solution of a three
      dimensional multispecies diffuse interface model of tumor growth, which was
      derived in (Wise et al., J. Theor. Biol. 253 (2008)) and used to study the
      development of glioma in (Frieboes et al., NeuroImage 37 (2007) and tumor
      invasion in (Bearer et al., Cancer Research, 69 (2009)) and (Frieboes et al., J.
      Theor. Biol. 264 (2010)). The model has a thermodynamic basis, is related to
      recently developed mixture models, and is capable of providing a detailed
      description of tumor progression. It utilizes a diffuse interface approach,
      whereby sharp tumor boundaries are replaced by narrow transition layers that
      arise due to differential adhesive forces among the cell-species. The model
      consists of fourth-order nonlinear advection-reaction-diffusion equations (of
      Cahn-Hilliard-type) for the cell-species coupled with reaction-diffusion
      equations for the substrate components. Numerical solution of the model is
      challenging because the equations are coupled, highly nonlinear, and numerically
      stiff. In this paper we describe a fully adaptive, nonlinear multigrid/finite
      difference method for efficiently solving the equations. We demonstrate the
      convergence of the algorithm and we present simulations of tumor growth in 2D and
      3D that demonstrate the capabilities of the algorithm in accurately and
      efficiently simulating the progression of tumors with complex morphologies.

PMID- 21076665
TI  - Photoluminescence Study of Low Thermal Budget III-V Nanostructures on Silicon by
      Droplet Epitaxy.
AB  - We present of a detailed photoluminescence characterization of high efficiency
      GaAs/AlGaAs quantum nanostructures grown on silicon substrates. The whole process
      of formation of the GaAs/AlGaAs active layer was realized via droplet epitaxy and
      migration enhanced epitaxy maintaining the growth temperature <=350 degrees C,
      thus resulting in a low thermal budget procedure compatible with back-end
      integration of the fabricated materials on integrated circuits. 

PMID- 21076666
TI  - The Characteristics of Seebeck Coefficient in Silicon Nanowires Manufactured by
      CMOS Compatible Process.
AB  - Silicon nanowires are patterned down to 30 nm using complementary metal-oxide
      semiconductor (CMOS) compatible process. The electrical conductivities of n-/p
      leg nanowires are extracted with the variation of width. Using this structure,
      Seebeck coefficients are measured. The obtained maximum Seebeck coefficient
      values are 122 MUV/K for p-leg and -94 MUV/K for n-leg. The maximum attainable
      power factor is 0.74 mW/m K(2) at room temperature. 

PMID- 21076667
TI  - Synthesis of Heterogeneous Li(4)Ti(5)O(12) Nanostructured Anodes with Long-Term
      Cycle Stability.
AB  - The 0D-1D Lithium titanate (Li(4)Ti(5)O(12)) heterogeneous nanostructures were
      synthesized through the solvothermal reaction using lithium hydroxide monohydrate
      (Li(OH).H(2)O) and protonated trititanate (H(2)Ti(3)O(7)) nanowires as the
      templates in an ethanol/water mixed solvent with subsequent heat treatment. A
      scanning electron microscope (SEM) and a high resolution transmission electron
      microscope (HRTEM) were used to reveal that the Li(4)Ti(5)O(12) powders had 0D-1D
      heterogeneous nanostructures with nanoparticles (0D) on the surface of wires
      (1D). The composition of the mixed solvents and the volume ratio of ethanol
      modulated the primary particle size of the Li(4)Ti(5)O(12) nanoparticles. The
      Li(4)Ti(5)O(12) heterogeneous nanostructures exhibited good capacity retention of
      125 mAh/g after 500 cycles at 1C and a superior high-rate performance of 114
      mAh/g at 20C.

PMID- 21076668
TI  - Pesticide Leaching from Agricultural Fields with Ridges and Furrows.
AB  - In the evaluation of the risk of pesticide leaching to groundwater, the soil
      surface is usually assumed to be level, although important crops like potato are
      grown on ridges. A fraction of the water from rainfall and sprinkler irrigation
      may flow along the soil surface from the ridges to the furrows, thus bringing
      about an extra load of water and pesticide on the furrow soil. A survey of the
      literature reveals that surface-runoff from ridges to furrows is a well-known
      phenomenon but that hardly any data are available on the quantities of water and
      pesticide involved. On the basis of a field experiment with additional sprinkler
      irrigation, computer simulations were carried out with the Pesticide Emission
      Assessment at Regional and Local scales model for separate ridge and furrow
      systems in a humic sandy potato field. Breakthrough curves of bromide ion (as a
      tracer for water flow) and carbofuran (as example pesticide) were calculated for
      1-m depth in the field. Bromide ion leached comparatively fast from the furrow
      system, while leaching from the ridge system was slower showing a maximum
      concentration of about half of that for the furrow system. Carbofuran
      breakthrough from the furrow system began about a month after application and
      increased steadily to substantial concentrations. Because the transport time of
      carbofuran in the ridge soil was much longer, no breakthrough occurred in the
      growing season. The maximum concentration of carbofuran leaching from the ridge
      furrow field was computed to be a factor of six times as high as that computed
      for the corresponding level field. The study shows that the risk of leaching of
      pesticides via the furrow soil can be substantially higher than that via the
      corresponding level field soil.

PMID- 21076669
TI  - Synthesis and Application of Carbon-Iron Oxide Microspheres' Black Pigments in
      Electrophoretic Displays.
AB  - Carbon-iron oxide microspheres' black pigments (CIOMBs) had been prepared via
      ultrasonic spray pyrolysis of aqueous solutions containing ferrous chloride and
      glucose. Due to the presence of carbon, CIOMBs not only exhibited remarkably acid
      resistance, but also could be well dispersed in both polar solvents and nonpolar
      solvent. Finally, dispersions of hollow CIOMBs in tetrachloroethylene had
      successfully been applied in electrophoretic displays. 

PMID- 21076670
TI  - Magnetic Behavior of Surface Nanostructured 50-nm Nickel Thin Films.
AB  - Thermally evaporated 50-nm nickel thin films coated on borosilicate glass
      substrates were nanostructured by excimer laser (0.5 J/cm(2), single shot), DC
      electric field (up to 2 kV/cm) and trench-template assisted technique.
      Nanoparticle arrays (anisotropic growth features) have been observed to form in
      the direction of electric field for DC electric field treatment case and ruptured
      thin film (isotropic growth features) growth for excimer laser treatment case.
      For trench-template assisted technique; nanowires (70-150 nm diameters) have
      grown along the length of trench template. Coercive field and saturation
      magnetization are observed to be strongly dependent on nanostructuring
      techniques. 

PMID- 21076671
TI  - Field Dependence of the Spin Relaxation Within a Film of Iron Oxide Nanocrystals
      Formed via Electrophoretic Deposition.
AB  - The thermal relaxation of macrospins in a strongly interacting thin film of
      spinel-phase iron oxide nanocrystals (NCs) is probed by vibrating sample
      magnetometry (VSM). Thin films are fabricated by depositing FeO/Fe(3)O(4) core
      shell NCs by electrophoretic deposition (EPD), followed by sintering at 400
      degrees C. Sintering transforms the core-shell structure to a uniform spinel
      phase, which effectively increases the magnetic moment per NC. Atomic force
      microscopy (AFM) confirms a large packing density and a reduced inter-particle
      separation in comparison with colloidal assemblies. At an applied field of 25 Oe,
      the superparamagnetic blocking temperature is T(B) (SP) ~ 348 K, which is much
      larger than the Neel-Brown approximation of T(B) (SP) ~ 210 K. The enhanced value
      of T(B) (SP) is attributed to strong dipole-dipole interactions and local
      exchange coupling between NCs. The field dependence of the blocking temperature,
      T(B) (SP)(H), is characterized by a monotonically decreasing function, which is
      in agreement with recent theoretical models of interacting macrospins. 

PMID- 21076672
TI  - Aqueous-Phase Synthesis of Silver Nanodiscs and Nanorods in Methyl Cellulose
      Matrix: Photophysical Study and Simulation of UV-Vis Extinction Spectra Using DDA
      Method.
AB  - We present a very simple and effective way for the synthesis of tunable coloured
      silver sols having different morphologies. The procedure is based on the seed
      mediated growth approach where methyl cellulose (MC) has been used as soft
      template in the growth solution. Nanostructures of varying morphologies as well
      as colour of the silver sols are controlled by altering the concentration of
      citrate in the growth solution. Similar to the polymers in the solution, citrate
      ions also dynamically adsorbed on the growing silver nanoparticles and promote
      one (1-D) and two-dimensional (2-D) growth of nanoparticles. Silver
      nanostructures are characterized using UV-vis and HR-TEM spectroscopic study.
      Simulation of the UV-vis extinction spectra of our synthesized silver
      nanostructures has been carried out using discrete dipole approximation (DDA)
      method. 

PMID- 21076673
TI  - Multi-Directional Growth of Aligned Carbon Nanotubes Over Catalyst Film Prepared
      by Atomic Layer Deposition.
AB  - The structure of vertically aligned carbon nanotubes (CNTs) severely depends on
      the properties of pre-prepared catalyst films. Aiming for the preparation of
      precisely controlled catalyst film, atomic layer deposition (ALD) was employed to
      deposit uniform Fe(2)O(3) film for the growth of CNT arrays on planar substrate
      surfaces as well as the curved ones. Iron acetylacetonate and ozone were
      introduced into the reactor alternately as precursors to realize the formation of
      catalyst films. By varying the deposition cycles, uniform and smooth Fe(2)O(3)
      catalyst films with different thicknesses were obtained on Si/SiO(2) substrate,
      which supported the growth of highly oriented few-walled CNT arrays. Utilizing
      the advantage of ALD process in coating non-planar surfaces, uniform catalyst
      films can also be successfully deposited onto quartz fibers. Aligned few-walled
      CNTs can be grafted on the quartz fibers, and they self-organized into a leaf
      shaped structure due to the curved surface morphology. The growth of aligned CNTs
      on non-planar surfaces holds promise in constructing hierarchical CNT
      architectures in future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of
      this article (doi:10.1007/s11671-010-9676-0) contains supplementary material,
      which is available to authorized users.

PMID- 21076674
TI  - Hollow Nanostructured Anode Materials for Li-Ion Batteries.
AB  - Hollow nanostructured anode materials lie at the heart of research relating to Li
      ion batteries, which require high capacity, high rate capability, and high
      safety. The higher capacity and higher rate capability for hollow nanostructured
      anode materials than that for the bulk counterparts can be attributed to their
      higher surface area, shorter path length for Li(+) transport, and more freedom
      for volume change, which can reduce the overpotential and allow better reaction
      kinetics at the electrode surface. In this article, we review recent research
      activities on hollow nanostructured anode materials for Li-ion batteries,
      including carbon materials, metals, metal oxides, and their hybrid materials. The
      major goal of this review is to highlight some recent progresses in using these
      hollow nanomaterials as anode materials to develop Li-ion batteries with high
      capacity, high rate capability, and excellent cycling stability. 

PMID- 21076675
TI  - Formation of ZnO Micro-Flowers Prepared via Solution Process and their
      Antibacterial Activity.
AB  - This paper presents the fabrication and characterization of zinc oxide micro
      flowers and their antibacterial activity. The micro-flowers of zinc oxide
      composed of hexagonal nanorods have been prepared via solution process using
      precursor zinc acetate di-hydrate and sodium hydroxide in 3 h of refluxing time
      at ~90 degrees C. The antibacterial activities of grown micro-flowers were
      investigated against four pathogenic bacteria namely S. aureus, E. coli, S.
      typhimurium and K. pneumoniae by taking five different concentrations (5-45
      MUg/ml) of ZnO micro-flowers (ZnO-MFs). Our investigation reveals that at lowest
      concentration of ZnO-MFs solution inhibiting the growth of microbial strain which
      was found to be 5 MUg/ml for all the tested pathogens. Additionally, on the basis
      of morphological and chemical observations, a chemical reaction mechanism of ZnO
      MFs composed of hexagonal nanorods was also proposed. 

PMID- 21076676
TI  - Assessment of Microwave/UV/O(3) in the Photo-Catalytic Degradation of Bromothymol
      Blue in Aqueous Nano TiO(2) Particles Dispersions.
AB  - In this study, a microwave/UV/TiO(2)/ozone/H(2)O(2) hybrid process system, in
      which various techniques that have been used for water treatment are combined, is
      evaluated to develop an advanced technology to treat non-biodegradable water
      pollutants efficiently. In particular, the objective of this study is to develop
      a novel advanced oxidation process that overcomes the limitations of existing
      single-process water treatment methods by adding microwave irradiation to
      maximize the formation of active intermediate products, e.g., OH radicals, with
      the aid of UV irradiation by microwave discharge electrodeless lamp, photo
      catalysts, and auxiliary oxidants. The results of photo-catalytic degradation of
      BTB showed that the decomposition rate increased with the TiO(2) particle dosages
      and microwave intensity. When an auxiliary oxidant such as ozone or hydrogen
      peroxide was added to the microwave-assisted photo-catalysis, however, a synergy
      effect that enhanced the reaction rate considerably was observed.

PMID- 21076677
TI  - An Antireflective Nanostructure Array Fabricated by Nanosilver Colloidal
      Lithography on a Silicon Substrate.
AB  - An alternative method is presented for fabricating an antireflective
      nanostructure array using nanosilver colloidal lithography. Spin coating was used
      to produce the multilayered silver nanoparticles, which grew by self-assembly and
      were transformed into randomly distributed nanosilver islands through the
      thermodynamic action of dewetting and Oswald ripening. The average size and
      coverage rate of the islands increased with concentration in the range of 50-90
      nm and 40-65%, respectively. The nanosilver islands were critically affected by
      concentration and spin speed. The effects of these two parameters were
      investigated, after etching and wet removal of nanosilver residues. The
      reflection nearly disappeared in the ultraviolet wavelength range and was 17% of
      the reflection of a bare silicon wafer in the visible range. 

PMID- 21076678
TI  - Nanoparticle Network Formation in Nanostructured and Disordered Block Copolymer
      Matrices.
AB  - Incorporation of nanoparticles composed of surface-functionalized fumed silica
      (FS) or native colloidal silica (CS) into a nanostructured block copolymer yields
      hybrid nanocomposites whose mechanical properties can be tuned by nanoparticle
      concentration and surface chemistry. In this work, dynamic rheology is used to
      probe the frequency and thermal responses of nanocomposites composed of a
      symmetric poly(styrene-b-methyl methacrylate) (SM) diblock copolymer and varying
      in nanoparticle concentration and surface functionality. At sufficiently high
      loading levels, FS nanoparticle aggregates establish a load-bearing colloidal
      network within the copolymer matrix. Transmission electron microscopy images
      reveal the morphological characteristics of the nanocomposites under these
      conditions. 

PMID- 21076679
TI  - New Directions in the Development of Population Estimates in the United States?
AB  - The advent of a continuously updated Master Area File (MAF) following the 2000
      census represents an information resource that can be tapped for purposes of
      developing timely, cost-effective, and precise population estimates for even the
      smallest of geographical units (e.g., census blocks). We argue that the MAF can
      be enhanced (EMAF) for these purposes. In support of our argument we describe a
      set of activities needed to develop EMAF, each of which is well within the
      current capabilities of the U.S. Census Bureau and discuss various costs and
      benefits of each. We also describe how EMAF would provide population estimates
      containing a wide range of demographic (e.g., age, race, and sex) and socio
      economic characteristics (e.g., educational attainment, income, and employment).
      As such, it could largely negate and eliminate the need for many of the
      traditional demographic methods of population estimation and possibly reduce the
      number of sample surveys. We identify important challenges that must be
      surmounted in order to realize EMAF and make suggestions for doing so. We
      conclude by noting that the idea of the EMAF could be of interest to other
      countries with MAF files and strong administrative records systems that, like the
      United States, are facing the challenge of producing good population information
      in the face of increasing census costs.

PMID- 21076680
TI  - Spontaneous epiglottic hematoma secondary to supratherapeutic anticoagulation.
AB  - Hemorrhage into the soft tissues of the airway represents a potentially life
      threatening complication of long-term anticoagulation. We report the case of a
      chronically anticoagulated 37-year-old male who developed a spontaneous hematoma
      of the epiglottis secondary to a supra-therapeutic INR. Epiglottic hematoma
      should be considered in the differential of any anticoagulated patient presenting
      with upper airway compromise. The airway should be secured in a controlled
      fashion, and the coagulopathy should be rapidly corrected.

PMID- 21076682
TI  - THE QUALITATIVE STATUS OF THE ONKOI IN ASCLEPIADES' THEORY OF MATTER.
AB  - The medical and philosophical system of Asclepiades of Bithynia (fl. later second
      century BC)(1) has been the subject of considerable controversy.(2) His physical
      theory of anarmoi onkoi in particular has seen intense debate, and although many
      of its broader features appear to be fairly well established, many of its most
      fundamental details remain obscure. Perhaps somewhat paradoxically, some of the
      most important work carried out on Asclepiades has been explicitly focused
      instead on Heraclides of Pontus,(3) the reconstruction of whose physical theory
      has often proceeded on the assumption that this was largely replicated by
      Asclepiades some two centuries later. But to a great extent the Asclepiadean
      debate has been framed in terms of the question of his intellectual debts to
      ancient atomism, and Epicureanism in particular, and in this respect the present
      study will be no different.(4) The most recent scholarship has been sharply
      divided over this question. Vallance has emphasized the principally medical
      context of Asclepiades' system, and made the case that the frangibility of the
      onkoi marks such a fundamental divergence from Epicurus' atomism that any
      influence from Epicurean physics should be rejected, and that we should look
      instead especially to Erasistratus.(5) Casadei, however, following on to a
      certain extent from the work of Pigeaud, has rightly drawn attention to the
      tendency in Vallance's exposition to suppress a number of fundamental elements of
      Asclepiades' doctrine which are undeniably also distinguishing features of
      Epicurean philosophy.(6) The most significant of these include his particulate
      theory of matter, his antiteleological conception of nature, and his rejection of
      any theory of qualitative change. But these correspondences would certainly not
      be sufficient to qualify Asclepiades' system simply as a reproduction of
      Epicureanism, and there is clear evidence that Asclepiades stood in opposition to
      Epicurus in certain fundamental respects. In a recent study which has done much
      to establish Asclepiades' credentials as a philosopher, focusing especially on
      his philosophy of mind, Polito has underlined certain distinctly non-Epicurean
      elements in his system, such as his radical determinism and his denial of a
      localized ruling-part-of-the-soul.(7) It thus seems clear that, despite some
      important parallels between their systems, Asclepiades cannot be regarded as an
      Epicurean physician. The evidence we have for his doctrine, and the authority
      which was accorded him by later writers, clearly attests to his status as an
      independent and innovative thinker in his own right. While Asclepiades' theory
      must, in my view, be analysed within the context of the Epicurean atomistic
      tradition, it must equally be acknowledged that any identifiable relationship
      between Epicurus and Asclepiades is likely to be one of considerable
      complexity.In this paper I shall attempt to explore further the nature of the
      relationship between Epicurus and Asclepiades by examining some aspects of the
      latter's theory of matter. Given the widespread disagreement about his theory in
      general, I propose to focus on a fundamental question which I believe the extant
      evidence allows us to answer with a satisfactory degree of certainty, namely what
      Asclepiades' position was on the qualitative status of his onkoi. In Section I I
      shall analyse four passages which have a direct bearing on this question, from
      Caelius Aurelianus, Galen, Sextus Empiricus, and Calcidius respectively. I shall
      argue here that this position was in its details substantially the same as
      Epicurus' with regard to his atoms. It must be stressed that it is only in
      details that we can make such comparisons, since we have no surviving testimony
      which recounts Asclepiades' arguments or broader reasons for holding such a
      position. Nevertheless, in Section II I shall argue that these identifiable
      similarities in their respective doctrines on the qualities of their elements
      were more than superficial or incidental, and strongly suggest that Asclepiades
      and Epicurus shared certain premisses which were fundamental to their physics,
      which might then be used to contextualize and elucidate some of the more
      idiosyncratic and apparently unique parts of Asclepiades' system. This will lead
      me to suggest an interpretation of an important piece of evidence which may
      confirm that Asclepiades was reacting in a direct and critical way to certain
      aspects of Epicurus' physical doctrine.

PMID- 21076681
TI  - Eosinophilic cholangitis and cholangiopathy: a sheep in wolves clothing.
AB  - BACKGROUND: Eosinophilic cholangitis (EC) is a rare benign disorder of the
      biliary tract which can cause biliary obstruction. Similar to other disease
      processes involving the bile ducts, this disorder can pose a difficult diagnostic
      challenge as it can mimic cholangiocarcinoma. METHODS: A systematic search of the
      scientific literature was carried out using PubMed to access all publications
      related to EC. Search keywords that were utilized included "eosinophilic
      cholangitis," "etiology," "treatment," and "obstructive jaundice." Results.
      Twenty-three cases of EC have been reported. Nineteen patients (82.6%) who
      presented with EC remain disease-free; 15 of these 19 patients (78.9%) with
      followup time remain disease-free at a mean of 9.7 months (range, 2-24 months).
      CONCLUSION: EC is a rare form of biliary obstruction which can masquerade as a
      malignancy. Unlike cholangiocarcinoma, EC occurs more commonly in younger
      patients and in men. Most patients will require surgical treatment.

PMID- 21076683
TI  - S100B Protein in the Nervous System and Cardiovascular Apparatus in Normal and
      Pathological Conditions.

PMID- 21076685
TI  - Fast Numerical Solutions of Patient-Specific Blood Flows in 3D Arterial Systems.
AB  - The study of hemodynamics in arterial models constructed from patient-specific
      medical images requires the solution of the incompressible flow equations in
      geometries characterized by complex branching tubular structures. The main
      challenge with this kind of geometries is that the convergence rate of the
      pressure Poisson solver is dominated by the graph depth of the computational
      grid. This paper presents a deflated preconditioned conjugate gradients (DPCG)
      algorithm for accelerating the pressure Poisson solver. A subspace deflation
      technique is used to approximate the lowest eigenvalues along tubular domains.
      This methodology was tested with an idealized cylindrical model and three patient
      specific models of cerebral arteries and aneurysms constructed from medical
      images. For these cases, the number of iterations decreased by up to a factor of
      16, while the total CPU time was reduced by up to 4 times when compared with the
      standard PCG solver.

PMID- 21076684
TI  - New insights in the management of antipsychotics in the treatment of
      schizophrenia in a patient with prolactinoma: a case report and review of the
      literature.
AB  - Prolactinomas are the commonest pituitary adenomas and the major pathological
      cause of hyperprolactinaemia. Symptomatic prolactinomas are treated mainly by
      dopamine agonists; surgery and radiotherapy are options for nonresponders.
      Schizophrenia treatment is based on antipsychotics, which acts mainly at
      serotonergic and dopaminergic systems. We report a case of a 39-year-old
      schizophrenic male patient that was diagnosed with a macroprolactinoma 8 years
      after his first psychotic episode. The association of Schizophrenia and
      prolactinoma represents a clinical challenge once the treatment of one disease
      can exacerbate the symptoms of the other.

PMID- 21076686
TI  - Carbamazepine-Induced Stevens-Johnson Syndrome Sparing the Skin Previously
      Affected by Herpes Zoster Infection in a Patient with Systemic Lupus
      Erythematosus: A Reverse Isotopic Phenomenon.
AB  - The reverse isotopic response is a rarely encountered phenomenon. The spared
      lesions are various and mainly inflammatory in nature, with herpes zoster
      infection being the most common. A novel case of Stevens-Johnson syndrome
      triggered by carbamazepine sparing the skin area previously affected by herpes
      zoster infection in a 39-year-old Indian female with systemic lupus erythematosus
      is documented. Several features as well as possible pathomechanisms that bear
      discussion have emerged from this case documentation. These may be related to the
      virus immunity, the underlying autoimmune disease (systemic lupus erythematosus)
      and/or drug metabolism.

PMID- 21076687
TI  - Dermoscopy of Pitted Keratolysis.
AB  - Irritated hyperhidrotic soles with multiple small pits are pathognomonic for
      pitted keratolysis (PK). Here we show the dermatoscopic view of typical pits that
      can ensure the diagnosis. PK is a plantar infection caused by Gram-positive
      bacteria, particularly Corynebacterium. Increases in skin surface pH,
      hyperhidrosis, and prolonged occlusion allow these bacteria to proliferate. The
      diagnosis is fundamentally clinical and treatment generally consists of a
      combination of hygienic measures, correcting plantar hyperhidrosis and topical
      antimicrobials.

PMID- 21076688
TI  - Conjunctival Melanoma: A New Clinical and Therapeutical Approach.
AB  - Melanoma involving the conjunctiva is extremely rare. Graver prognosis has been
      reported with primary conjunctival melanoma than with their cutaneous
      counterparts [Collin et al.: Aust N Z J Ophthalmol 1986;14:29-34]. Among
      conjunctival melanomas, two significant risk factors for tumour-related death
      have been identified: (i) age older than 55 years and (ii) unfavourable tumour
      location (caruncle, cornea, fornix, palpebral conjunctiva) [Werschnik and
      Lommatzsch: Am J Clin Oncol 2002;25:248-255]. Here we present a rare case of
      lentigo maligna involving the palpebral, bulbar conjunctiva and the caruncle. We
      describe dermoscopic patterns observed and the use of a novel ocular melanoma
      therapy with topical imiquimod.

PMID- 21076689
TI  - Vitiligo at Injection Site of PEG-IFN-alpha 2a in Two Patients with Chronic
      Hepatitis C: Case Report and Literature Review.
AB  - A 72-year-old female and a 57-year-old male with chronic hepatitis C were treated
      with a combination therapy of pegylated interferon (PEG-IFN)-alpha 2a (180 MUg
      s.c. once a week) and ribavirin (1,000 mg orally daily). This resulted in the
      destruction of melanocytes at the injection site in both patients. In the male
      patient, the depigmentation progressed to the surrounding skin area. The
      dermatologist concurred with vitiligo as the diagnosis in both patients.
      Injection and surrounding site vitiligo associated with PEG-IFN-alpha 2b
      treatment for hepatitis C was noticed in previous case studies. For the first
      time, the case reports below highlight the same immunological adverse event
      secondary to PEG IFN-alpha 2a/ribavirin combination therapy and explain, in part,
      the complex interaction between host immune response and viral genotype. In
      addition, we systematically review drug-induced vitiligo and autoimmune diseases
      associated with the depigmentation disorder.

PMID- 21076690
TI  - Diffeomorphic Sulcal Shape Analysis for Cortical Surface Registration.
AB  - We present an intrinsic framework for constructing sulcal shape atlases on the
      human cortex. We propose the analysis of sulcal and gyral patterns by
      representing them by continuous open curves in R(3). The space of such curves,
      also termed as the shape manifold is equipped with a Riemannian L(2) metric on
      the tangent space, and shows desirable properties while matching shapes of sulci.
      On account of the spherical nature of the shape space, geodesics between shapes
      can be computed analytically. Additionally, we also present an optimization
      approach that computes geodesics in the quotient space of shapes modulo rigid
      rotations and reparameterizations. We also integrate the elastic shape model into
      a surface registration framework for a population of 176 subjects, and show a
      considerable improvement in the constructed surface atlases.

PMID- 21076692
TI  - Intrinsic Bayesian Active Contours for Extraction of Object Boundaries in Images.
AB  - We present a framework for incorporating prior information about high-probability
      shapes in the process of contour extraction and object recognition in images.
      Here one studies shapes as elements of an infinite-dimensional, non-linear
      quotient space, and statistics of shapes are defined and computed intrinsically
      using differential geometry of this shape space. Prior models on shapes are
      constructed using probability distributions on tangent bundles of shape spaces.
      Similar to the past work on active contours, where curves are driven by vector
      fields based on image gradients and roughness penalties, we incorporate the prior
      shape knowledge in the form of vector fields on curves. Through experimental
      results, we demonstrate the use of prior shape models in the estimation of object
      boundaries, and their success in handling partial obscuration and missing data.
      Furthermore, we describe the use of this framework in shape-based object
      recognition or classification.

PMID- 21076693
TI  - The Efficacy of Repeated Reading and Wide Reading Practice for High School
      Students with Severe Reading Disabilities.
AB  - This experimental study was conducted to examine the efficacy of repeated reading
      and wide reading practice interventions for high school students with severe
      reading disabilities. Effects on comprehension, fluency, and word reading were
      evaluated. Participants were 96 students with reading disabilities in grades 9
      12. Students were paired within classes and pairs were randomly assigned to one
      of three groups: repeated reading (N = 33), wide reading (N = 34), or typical
      instruction (N = 29). Intervention was provided daily for approximately 15-20
      minutes for 10 weeks. Results indicated no overall statistically significant
      differences for any condition, with effect sizes ranging from -.31 to .27.
      Findings do not support either approach for severely impaired readers at the high
      school level. We hypothesize that these students require more intensive
      interventions that include direct and explicit instruction in word- and text
      level skills as well as engaged reading practice with effective feedback.

PMID- 21076691
TI  - Arabidopsis Protein Repair L-Isoaspartyl Methyltransferases: Predominant
      Activities at Lethal Temperatures.
AB  - Protein L-isoaspartyl (D-aspartyl) O-methyltransferases (EC 2.1.1.77; PIMT or
      PCMT) are enzymes that initiate the full or partial repair of damaged L-aspartyl
      and L-asparaginyl residues, respectively. These enzymes are found in most
      organisms and maintain a high degree of sequence conservation. Arabidopsis
      thaliana (Arabidopsis L. Heynh.) is unique among eukaryotes in that it contains
      two genes, rather than one, that encode PIMT isozymes. We describe a novel
      Arabidopsis PIMT isozyme, designated AtPIMT2alphaomega, encoded by the PIMT2 gene
      (At5g50240). We characterized the enzymatic activity of the recombinant
      AtPIMT2alphaomega in comparison to the other AtPIMT2 isozymes, AtPIMT1, and to
      the human PCMT ortholog, to better understand its role in Arabidopsis. All
      Arabidopsis PIMT isozymes are active over a relatively wide pH range. For
      AtPIMT2alphaomega maximal activity is observed at 50  degrees C (a lethal
      temperature for Arabidopsis); this activity is almost ten times greater than the
      activity at the growth temperature of 25  degrees C. Interestingly, enzyme
      activity decreases after pre-incubation at temperatures above 30 degrees C. A
      similar situation is found for the recombinant AtPIMT2psi and the AtPIMT2omega
      isozymes, as well as for the AtPIMT1 and human PCMT1 enzymes. These results
      suggest that the short-term ability of these methyltransferases to initiate
      repair under extreme temperature conditions may be a common feature of both the
      plant and animal species.

PMID- 21076694
TI  - NONPARAMETRIC ESTIMATION OF GENEWISE VARIANCE FOR MICROARRAY DATA.
AB  - Estimation of genewise variance arises from two important applications in
      microarray data analysis: selecting significantly differentially expressed genes
      and validation tests for normalization of microarray data. We approach the
      problem by introducing a two-way nonparametric model, which is an extension of
      the famous Neyman-Scott model and is applicable beyond microarray data. The
      problem itself poses interesting challenges because the number of nuisance
      parameters is proportional to the sample size and it is not obvious how the
      variance function can be estimated when measurements are correlated. In such a
      high-dimensional nonparametric problem, we proposed two novel nonparametric
      estimators for genewise variance function and semiparametric estimators for
      measurement correlation, via solving a system of nonlinear equations. Their
      asymptotic normality is established. The finite sample property is demonstrated
      by simulation studies. The estimators also improve the power of the tests for
      detecting statistically differentially expressed genes. The methodology is
      illustrated by the data from MicroArray Quality Control (MAQC) project.

PMID- 21076695
TI  - Growth of Inclined GaAs Nanowires by Molecular Beam Epitaxy: Theory and
      Experiment.
AB  - The growth of inclined GaAs nanowires (NWs) during molecular beam epitaxy (MBE)
      on the rotating substrates is studied. The growth model provides explicitly the
      NW length as a function of radius, supersaturations, diffusion lengths and the
      tilt angle. Growth experiments are carried out on the GaAs(211)A and GaAs(111)B
      substrates. It is found that 20 degrees  inclined NWs are two times longer in
      average, which is explained by a larger impingement rate on their sidewalls. We
      find that the effective diffusion length at 550 degrees C amounts to 12 nm for
      the surface adatoms and is more than 5,000 nm for the sidewall adatoms.
      Supersaturations of surface and sidewall adatoms are also estimated. The obtained
      results show the importance of sidewall adatoms in the MBE growth of NWs,
      neglected in a number of earlier studies. 

PMID- 21076696
TI  - Silicon and Germanium Nanostructures for Photovoltaic Applications: Ab-Initio
      Results.
AB  - Actually, most of the electric energy is being produced by fossil fuels and great
      is the search for viable alternatives. The most appealing and promising
      technology is photovoltaics. It will become truly mainstream when its cost will
      be comparable to other energy sources. One way is to significantly enhance device
      efficiencies, for example by increasing the number of band gaps in multijunction
      solar cells or by favoring charge separation in the devices. This can be done by
      using cells based on nanostructured semiconductors. In this paper, we will
      present ab-initio results of the structural, electronic and optical properties of
      (1) silicon and germanium nanoparticles embedded in wide band gap materials and
      (2) mixed silicon-germanium nanowires. We show that theory can help in
      understanding the microscopic processes important for devices performances. In
      particular, we calculated for embedded Si and Ge nanoparticles the dependence of
      the absorption threshold on size and oxidation, the role of crystallinity and, in
      some cases, the recombination rates, and we demonstrated that in the case of
      mixed nanowires, those with a clear interface between Si and Ge show not only a
      reduced quantum confinement effect but display also a natural geometrical
      separation between electron and hole. 

PMID- 21076697
TI  - Direct Interaction Between Gold Nanorods and Glucose.
AB  - In this work, we present the results of the study on the interactions between
      gold nanorods (GNRs) and glucose. The optical properties of GNRs have higher
      sensitivity to glucose compared with that of gold nanospheres. The long
      wavelength bands of the GNRs obviously decrease as the concentration of glucose
      increases. At high glucose concentrations, the absorption peak in long-wavelength
      bands almost disappears, and the absorption intensities corresponding to the
      transverse plasmon band are also decrease. These results suggest that glucose
      could seriously affect the optical properties of GNRs. A possible interaction
      mechanism between gold nanorods (GNRs) and glucose has been proposed.
      Furthermore, the influence of glucose on different amount GNRs also has been
      studied. 

PMID- 21076698
TI  - Nanosilver Colloids-Filled Photonic Crystal Arrays for Photoluminescence
      Enhancement.
AB  - For the improved surface plasmon-coupled photoluminescence emission, a more
      accessible fabrication method of a controlled nanosilver pattern array was
      developed by effectively filling the predefined hole array with nanosilver
      colloid in a UV-curable resin via direct nanoimprinting. When applied to a glass
      substrate for light emittance with an oxide spacer layer on top of the nanosilver
      pattern, hybrid emission enhancements were produced from both the localized
      surface plasmon resonance-coupled emission enhancement and the guided light
      extraction from the photonic crystal array. When CdSe/ZnS nanocrystal quantum
      dots were deposited as an active emitter, a total photoluminescence intensity
      improvement of 84% was observed. This was attributed to contributions from both
      the silver nanoparticle filling and the nanoimprinted photonic crystal array. 

PMID- 21076699
TI  - Fabrication of Coaxial Si(1-x)Ge(x) Heterostructure Nanowires by O(2) Flow
      Induced Bifurcate Reactions.
AB  - We report on bifurcate reactions on the surface of well-aligned Si(1-x)Ge(x)
      nanowires that enable fabrication of two different coaxial heterostructure
      nanowires. The Si(1-x)Ge(x) nanowires were grown in a chemical vapor transport
      process using SiCl(4) gas and Ge powder as a source. After the growth of
      nanowires, SiCl(4) flow was terminated while O(2) gas flow was introduced under
      vacuum. On the surface of nanowires was deposited Ge by the vapor from the Ge
      powder or oxidized into SiO(2) by the O(2) gas. The transition from deposition to
      oxidation occurred abruptly at 2 torr of O(2) pressure without any intermediate
      region and enables selectively fabricated Ge/Si(1-x)Ge(x) or SiO(2)/Si(1-x)Ge(x)
      coaxial heterostructure nanowires. The rate of deposition and oxidation was
      dominated by interfacial reaction and diffusion of oxygen through the oxide
      layer, respectively.

PMID- 21076700
TI  - Nanostructured Systems Containing Rutin: In Vitro Antioxidant Activity and
      Photostability Studies.
AB  - The improvement of the rutin photostability and its prolonged in vitro
      antioxidant activity were studied by means of its association with nanostructured
      aqueous dispersions. Rutin-loaded nanocapsules and rutin-loaded nanoemulsion
      showed mean particle size of 124.30 +/- 2.06 and 124.17 +/- 1.79, respectively,
      polydispersity index below 0.20, negative zeta potential, and encapsulation
      efficiency close to 100%. The in vitro antioxidant activity was evaluated by the
      formation of free radical .OH after the exposure of hydrogen peroxide to a UV
      irradiation system. Rutin-loaded nanostructures showed lower rutin decay rates
      [(6.1 +/- 0.6) 10(-3) and (5.1 +/- 0.4) 10(-3) for nanocapsules and nanoemulsion,
      respectively] compared to the ethanolic solution [(35.0 +/- 3.7) 10(-3) min(-1)]
      and exposed solution [(40.1 +/- 1.7) 10(-3) min(-1)] as well as compared to
      exposed nanostructured dispersions [(19.5 +/- 0.5) 10(-3) and (26.6 +/- 2.6) 10(
      3), for nanocapsules and nanoemulsion, respectively]. The presence of the
      polymeric layer in nanocapsules was fundamental to obtain a prolonged antioxidant
      activity, even if the mathematical modeling of the in vitro release profiles
      showed high adsorption of rutin to the particle/droplet surface for both
      formulations. Rutin-loaded nanostructures represent alternatives to the
      development of innovative nanomedicines. 

PMID- 21076701
TI  - Dimensional Effects on Densities of States and Interactions in Nanostructures.
AB  - We consider electrons in the presence of interfaces with different effective
      electron mass, and electromagnetic fields in the presence of a high-permittivity
      interface in bulk material. The equations of motion for these dimensionally
      hybrid systems yield analytic expressions for Green's functions and
      electromagnetic potentials that interpolate between the two-dimensional
      logarithmic potential at short distance, and the three-dimensional r(-1)
      potential at large distance. This also yields results for electron densities of
      states which interpolate between the well-known two-dimensional and three
      dimensional formulas. The transition length scales for interfaces of thickness L
      are found to be of order Lm/2m(*) for an interface in which electrons move with
      effective mass m(*), and Lepsilon(*)/2epsilon for a dielectric thin film with
      permittivity epsilon(*) in a bulk of permittivity epsilon. We can easily test the
      merits of the formalism by comparing the calculated electromagnetic potential
      with the infinite series solutions from image charges. This confirms that the
      dimensionally hybrid models are excellent approximations for distances r ? L/2. 

PMID- 21076702
TI  - Synthesis of Bio-Compatible SPION-based Aqueous Ferrofluids and Evaluation of
      RadioFrequency Power Loss for Magnetic Hyperthermia.
AB  - Bio-compatible magnetic fluids having high saturation magnetization find immense
      applications in various biomedical fields. Aqueous ferrofluids of
      superparamagnetic iron oxide nanoparticles with narrow size distribution, high
      shelf life and good stability is realized by controlled chemical co-precipitation
      process. The crystal structure is verified by X-ray diffraction technique.
      Particle sizes are evaluated by employing Transmission electron microscopy. Room
      temperature and low-temperature magnetic measurements were carried out with
      Superconducting Quantum Interference Device. The fluid exhibits good magnetic
      response even at very high dilution (6.28 mg/cc). This is an advantage for
      biomedical applications, since only a small amount of iron is to be metabolised
      by body organs. Magnetic field induced transmission measurements carried out at
      photon energy of diode laser (670 nm) exhibited excellent linear dichroism. Based
      on the structural and magnetic measurements, the power loss for the magnetic
      nanoparticles under study is evaluated over a range of radiofrequencies. 

PMID- 21076703
TI  - Solvothermal Synthesis, Structure and Optical Property of Nanosized CoSb(3)
      Skutterudite.
AB  - Binary skutterudite CoSb(3) nanoparticles were synthesized by solvothermal
      method. The nanostructuring of CoSb(3) material was achieved by the inclusion of
      various kinds of additives. X-ray diffraction examination indicated the formation
      of the cubic phase of CoSb(3). Structural analysis by transmission electron
      microscopy analysis further confirmed the formation of crystalline CoSb(3)
      nanoparticles with high purity. With the assistance of additives, CoSb(3)
      nanoparticles with size as small as 10 nm were obtained. The effect of the
      nanostructure of CoSb(3) on the UV-visible absorption and luminescence was
      studied. The nanosized CoSb(3) skutterudite may find application in developing
      thermoelectric devices with better efficiency.

PMID- 21076704
TI  - Intracellular ZnO Nanorods Conjugated with Protoporphyrin for Local Mediated
      Photochemistry and Efficient Treatment of Single Cancer Cell.
AB  - ZnO nanorods (NRs) with high surface area to volume ratio and biocompatibility is
      used as an efficient photosensitizer carrier system and at the same time
      providing intrinsic white light needed to achieve cancer cell necrosis. In this
      letter, ZnO nanorods used for the treatment of breast cancer cell (T47D) are
      presented. To adjust the sample for intracellular experiments, we have grown the
      ZnO nanorods on the tip of borosilicate glass capillaries (0.5 MUm diameter) by
      aqueous chemical growth technique. The grown ZnO nanorods were conjugated using
      protoporphyrin dimethyl ester (PPDME), which absorbs the light emitted by the ZnO
      nanorods. Mechanism of cytotoxicity appears to involve the generation of singlet
      oxygen inside the cell. The novel findings of cell-localized toxicity indicate a
      potential application of PPDME-conjugated ZnO NRs in the necrosis of breast
      cancer cell within few minutes. 

PMID- 21076705
TI  - Indium Tin Oxide@Carbon Core-Shell Nanowire and Jagged Indium Tin Oxide Nanowire.
AB  - This paper reports two new indium tin oxide (ITO)-based nanostructures, namely
      ITO@carbon core-shell nanowire and jagged ITO nanowire. The ITO@carbon core-shell
      nanowires (~50 nm in diameter, 1-5 MUm in length,) were prepared by a chemical
      vapor deposition process from commercial ITO nanoparticles. A carbon overlayer
      (~5-10 in thickness) was observed around ITO nanowire core, which was in situ
      formed by the catalytic decomposition of acetylene gas. This carbon overlayer
      could be easily removed after calcination in air at an elevated temperature of
      700 degrees C, thus forming jagged ITO nanowires (~40-45 nm in diameter). The
      growth mechanisms of ITO@carbon core-shell nanowire and jagged ITO nanowire were
      also suggested. 

PMID- 21076706
TI  - Cation-Induced Coiling of Vanadium Pentoxide Nanobelts.
AB  - Single-crystalline V(2)O(5).xH(2)O nanorings and microloops were chemically
      assembled via an ion-induced chemical spinning route in the designed hydrothermal
      system. The morphology and structure of products were investigated by means of
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM). X
      ray powder diffraction (XRD) measurement, energy-dispersive X-ray spectroscopy
      (EDS) microanalysis and thermal gravimetric analysis (TGA) revealed that the
      composition of nanorings and microloops is V(2)O(5).1.1H(2)O. For these oxide
      nanorings and microloops, the cation-induced coiling growth mechanism of vanadium
      pentoxide nanobelts has been proposed on the basis of crystallographic structure
      of vanadium pentoxide. Our proposed chemical spinning process and the rational
      solution-phase synthesis route can also be extended to prepare novel 1D materials
      with layered or more complex structures. 

PMID- 21076707
TI  - Single-dot Spectroscopy of GaAs Quantum Dots Fabricated by Filling of Self
      assembled Nanoholes.
AB  - We study the optical emission of single GaAs quantum dots (QDs). The QDs are
      fabricated by filling of nanoholes in AlGaAs and AlAs which are generated in a
      self-assembled fashion by local droplet etching with Al droplets. Using suitable
      process parameters, we create either uniform QDs in partially filled deep holes
      or QDs with very broad size distribution in completely filled shallow holes.
      Micro photoluminescence measurements of single QDs of both types establish sharp
      excitonic peaks. We measure a fine-structure splitting in the range of 22-40MUeV
      and no dependence on QD size. Furthermore, we find a decrease in exciton
      biexciton splitting with increasing QD size. 

PMID- 21076708
TI  - Characterisation and Skin Distribution of Lecithin-Based Coenzyme Q10-Loaded
      Lipid Nanocapsules.
AB  - The purpose of this study was to investigate the influence of the inner lipid
      ratio on the physicochemical properties and skin targeting of surfactant-free
      lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs). The smaller
      particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of
      CoQ10/GTCC (Caprylic/capric triglyceride); however, the zeta potential of CoQ10
      LNCs was above /- 60 mV/ with no distinct difference among them at different
      ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with
      the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the
      supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm,
      as verified by differential scanning calorimetry (DSC) in one heating-cooling
      cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by
      cryogenic transmission electron microscopy (Cryo-TEM). The skin penetration
      results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on
      the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial
      dermal targeting were achieved by the CoQ10-LNCs application. The highest
      fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These
      observations suggest that lecithin-based LNCs could be used as a promising
      topical delivery vehicle for lipophilic compounds. 

PMID- 21076709
TI  - Preferential Growth of Semiconducting Single-Walled Carbon Nanotubes on Substrate
      by Europium Oxide.
AB  - In this paper, we have demonstrated that europium oxide (Eu(2)O(3)) is a new type
      of active catalyst for single-walled carbon nanotubes (SWNTs) growth under
      suitable conditions. Both random SWNT networks and horizontally aligned SWNT
      arrays are efficiently grown on silicon wafers. The density of the SWNT arrays
      can be altered by the CVD conditions. This result further provides the
      experimental evidence that the efficient catalyst for SWNT growth is more size
      dependent than the catalysts themselves. Furthermore, the SWNTs from europium
      sesquioxides have compatibly higher quality than that from Fe/Mo catalyst. More
      importantly, over 80% of the nanotubes from Eu(2)O(3) are semiconducting SWNTs (s
      SWNTs), indicating the preferential growth of s-SWNTs from Eu(2)O(3). This new
      finding could open a way for selective growth of s-SWNTs, which can be used as
      high-current nanoFETs and sensors. Moreover, the successful growth of SWNTs by
      Eu(2)O(3) catalyst provides new experimental information for understanding the
      preferential growth of s-SWNTs from Eu(2)O(3), which may be helpful for their
      controllable synthesis. 

PMID- 21076710
TI  - Cabazitaxel, a new taxane with favorable properties.
AB  - Cabazitaxel is a new taxane characterized by convenient administration, a
      favorable pharmacokinetic and safety profile and a decreased propensity for P
      glycoprotein (Pgp)-mediated drug resistance. In preclinical studies cabazitaxel
      inhibited cell growth in a wide range of human cancer cell lines, including tumor
      models expressing Pgp. Phase I clinical trials established that the cabazitaxel
      side effect profile is similar to that reported for taxanes, with neutropenia and
      neuropathy being the most commonly reported toxicities. Further clinical studies
      have revealed that cabazitaxel is clinically active in women with taxaneresistant
      metastatic breast cancer and in men with metastatic castration-resistant prostate
      cancer previously treated with docetaxel. The TROPIC phase III trial concluded
      that, compared to mitoxantrone/prednisone, the combination cabazitaxel/prednisone
      conferred a statistically significantly longer overall survival in patients after
      treatment with a docetaxel-containing regimen, providing the basis for its FDA
      approval in 2010.

PMID- 21076711
TI  - Ceftaroline fosamil: a novel broad-spectrum cephalosporin.
AB  - Ceftaroline fosamil is a new extended-spectrum cephalosporin with activity
      against drug-resistant Grampositive pathogens such as methicillin-resistant
      Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae.
      At the same time, its Gramnegative spectrum of coverage includes common
      respiratory pathogens such as Haemophilus influenzae and Moraxella catarrhalis,
      as well as wild-type Enterobacteriaceae. In vivo efficacy for the treatment of
      experimental endocarditis, pneumonia, myositis and osteomyelitis has been
      demonstrated in animal models, while efficacy in the treatment of complicated
      skin and soft tissue infections and community-acquired pneumonia has been
      demonstrated in phase II and III clinical trials in humans. The drug is well
      tolerated and has a low rate of reported adverse events. The dose of ceftaroline
      fosamil used is 600 mg i.v. every 12 h for patients with normal renal function or
      mild renal dysfunction. In patients with moderate renal dysfunction, it has been
      suggested that ceftaroline fosamil be dosed at 400 mg i.v. over 60 min every 12
      h. Ceftaroline fosamil is still under review by the U.S. FDA, and when approved,
      will be one of the first commercially available beta-lactams with the ability to
      treat infections due to MRSA and other drug-resistant Gram-positive pathogens.

PMID- 21076712
TI  - The role of a new formulation of fenofibric acid in the treatment of mixed
      dyslipidemia in type 2 diabetes.
AB  - Diabetes, due to its multifactorial effects, increases the risk of developing
      cardiovascular disease. Dyslipidemia is an important modifiable risk factor.
      Mixed dyslipidemia (low high-density lipoprotein cholesterol [HDL-C], elevated
      triglycerides and a high percentage of small, dense lowdensity lipoprotein
      cholesterol [LDL-C]) is a common lipid disorder in diabetics and is considered
      especially atherogenic. Research suggests that in patients with dyslipidemia,
      combination therapy with fibrates and statins may be more effective than statin
      monotherapy alone. The choline salt of fenofibric acid (choline fibrate) is
      indicated for the treatment of mixed dyslipidemia, either as a single treatment
      or in combination with statin therapy. It does not require first-pass metabolism,
      but dissociates in the gastrointestinal tract into the pharmacologically active
      fenofibric acid. This new formulation of fenofibric acid in combination with a
      low or moderate dose of statin has been shown to be effective in increasing HDL-C
      and lowering triglycerides beyond that provided by statin monotherapy alone. The
      ACCORD trial failed to show a mortality or morbidity benefit after combination
      therapy, although the data suggested that combination therapy may benefit
      patients with mixed dyslipidemia.

PMID- 21076713
TI  - Pitavastatin - a novel therapeutic milestone.
AB  - Treatment for hypercholesterolemia aims to suppress the progression of early
      atherosclerotic changes and prevent the onset of future cardiovascular events.
      Drugs to treat hypercholesterolemia should thus have sufficient longterm lipid
      lowering and direct antiatherosclerotic effects. Pitavastatin is a 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) that was
      developed in Japan. In addition to its long-term lipid-lowering effects,
      pitavastatin also exerts pleiotropic effects against atherosclerotic changes.
      Although few studies have investigated the mechanism of pitavastatin, its
      pleiotropic effects have encouraged its use to treat both hypercholesterolemia
      and atherosclerosis. Pentraxin-related protein PTX3, a prototype protein of the
      pentraxin family, could serve as a novel useful blood marker to assess dynamic
      inflammation during the early atherosclerotic stages. This review clarifies the
      long-term lipid-lowering and antiatherosclerotic effects of pitavastatin.

PMID- 21076714
TI  - The dynamic nature of ventricular tachycardia initiation.
AB  - Initiation of ventricular tachycardia (VT) or ventricular fibrillation (VF)
      requires heterogeneity of the substrate. This heterogeneity has a stable/fixed
      component (structural or functional) and a dynamic component. The latter explains
      the random and sudden destabilization of the substrate and the initiation of VT
      or VF by a ventricular extra stimulus trigger. The main mechanisms of dynamic
      heterogeneity are discussed at the cellular level (action potential duration
      alternans and restitution and intracellular calcium cycling instability) and at
      the tissue level (conduction velocity restitution and concordant and discordant
      alternans). Better knowledge of dynamic factors in arrhythmogenesis has an
      overwhelming impact on both predicting malignant arrhythmias and changing the
      antiarrhythmic drug paradigm from suppressing triggers to modifying dynamic
      instability factors.

PMID- 21076715
TI  - Through the steps of history: a report from the Annual European Congress of
      Rheumatology (EULAR) (June 16-19, 2010 - Rome, Italy).
AB  - Rome is an open book to human history, and traveling from the city center to the
      Nuova Fiera da Roma, as most of this year's attendees to EULAR had to do to reach
      the congress site, is a voyage from the remains of the Roman Empire throughout
      the middle ages and across most of human history to the modern architecture that
      characterizes the new exposition facilities next to the airport of Fiumicino.
      EULAR offers a yearly development on therapies for diseases with a clear, direct
      negative impact on physical functioning of the sufferers, and this report will
      review most of the therapeutic novelties discussed this year.

PMID- 21076717
TI  - Daily low-dose folic acid supplementation does not prevent nitroglycerin-induced
      nitric oxide synthase dysfunction and tolerance: a human in vivo study.
AB  - INTRODUCTION: Continuous treatment with nitroglycerin (GTN) causes tolerance and
      endothelial dysfunction, both of which may involve endothelial nitric oxide
      synthase (eNOS) dysfunction. eNOS dysfunction may be linked to depletion of
      tetrahydrobiopterin, and folic acid may be involved in the regeneration of this
      cofactor. It has been demonstrated that 10 mg/day folic acid supplementation
      prevents the development of GTN tolerance and GTN-induced endothelial
      dysfunction. However, the efficacy of daily lower-dose folic acid supplementation
      for preventing these phenomena has not been investigated. OBJECTIVE: To determine
      the effect of 1 mg/day folic acid supplementation on responses to sustained GTN
      therapy. METHODS AND RESULTS: On visit 1, 20 healthy male volunteers were
      randomly assigned to receive either oral folic acid (1 mg/day) or placebo for one
      week in a double- blind study. All subjects also received continuous transdermal
      GTN (0.6 mg/h). On visit 2, forearm blood flow was measured using venous
      occlusion strain-gauge plethysmography in response to incremental intra-arterial
      infusions of acetylcholine, N-monomethyl-L-arginine and GTN. Subjects in both
      groups displayed significantly decreased responses to acetylcholine and N
      monomethyl-L-arginine infusions compared with a control group that received no
      treatment. Responses to GTN were also significantly diminished in both groups
      (P<0.05 for all). DISCUSSION: The present data demonstrate that daily
      supplementation with 1 mg folic acid does not prevent the development of GTN
      induced eNOS dysfunction or tolerance.

PMID- 21076718
TI  - Mechanical circulatory support with the ABIOMED BVS 5000: the Toronto General
      Hospital experience.
AB  - BACKGROUND: Acute hemodynamic collapse resulting in cardiogenic shock and
      impending end-organ failure is usually associated with certain death. The
      introduction of short-term mechanical circulatory support (MCS) devices offers
      potential therapy to these critically ill patients. The BVS 5000 device (ABIOMED
      Inc, USA) is widely used in the United States, but rarely in Canada, where device
      reimbursement remains a barrier. OBJECTIVE: To present the Toronto General
      Hospital's (Toronto, Ontario) initial five-year experience with this device to
      highlight the indications for use, common complications and overall success
      rates. METHODS AND RESULTS: The institutional MCS database from 2001 to 2006 was
      reviewed, and 18 patients who received 30 devices in a variety of configurations
      were identified. The most common support configuration consisted of biventricular
      support (n=12), followed by isolated left ventricular support (n=4) and isolated
      right ventricular support in two recipients of an implantable long-term left
      ventricular assist device. Overall survival to device explant or transplant was
      55% (n=10), of which five (50%) were successfully discharged from the hospital.
      The overall survival from device implant to hospital discharge was 28% (five of
      18). The most common cause of death was multisystem organ failure. CONCLUSIONS:
      MCS with the ABIOMED BVS 5000 can successfully resuscitate critically ill
      patients; however, earlier institution of this device would avoid irreversible
      end-organ injury, and lead to higher rates of device explant and hospital
      discharge. Short-term MCS devices should be available in all cardiac surgical
      centres in Canada to permit stabilization and evaluation of the acutely ill
      cardiac patient and subsequent management in a heart transplant facility.

PMID- 21076719
TI  - Time course of early changes in plasma markers of collagen turnover following
      percutaneous transluminal coronary angioplasty.
AB  - INTRODUCTION: Marked changes occur in the collagen framework of the heart
      following acute ischemia, which is associated with adverse ventricular
      remodelling. Plasma markers of collagen turnover are useful in the assessment of
      remodelling and have predictive value, but their exact temporal dynamics
      following ischemia are unclear. OBJECTIVE: To characterize the early temporal
      dynamics of plasma markers of collagen turnover in a human model of coronary
      artery occlusion. METHODS: Fourteen patients undergoing elective percutaneous
      coronary intervention (PCI) to a single coronary artery were recruited in
      addition to a control group of eight patients undergoing elective diagnostic
      coronary arteriography. Sequential assessment of plasma levels of procollagen
      type I carboxyterminal propeptide and C-telopeptide for type I collagen (CITP) as
      markers of synthesis and degradation, respectively, was performed over a 16 h
      period. RESULTS: The ischemic burden in the PCI group was high, with 13 of the 14
      patients demonstrating transient ST segment shift or positive troponin. Mean
      plasma levels of CITP on admission were 3.1 ng/mL and 3.0 ng/mL in the PCI and
      control groups, respectively (P value nonsignificant). There was a sequential
      increase in plasma CITP following PCI, peaking at 4.7 ng/mL at 16 h (P<0.01),
      with no change in the control group. There were no significant changes in plasma
      levels of procollagen type I carboxyterminal propeptide in either group.
      CONCLUSIONS: Plasma levels of CITP demonstrated early temporal dynamics of
      collagen degradation following transient coronary artery occlusion supporting the
      use of plasma markers of collagen turnover as an early tool in the assessment of
      the remodelling process following myocardial ischemia.

PMID- 21076720
TI  - Utility of three-dimensional echocardiography in assessing and predicting
      response to cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) can be a valuable treatment
      for heart failure. However, there are high nonresponse rates using current CRT
      inclusion criteria. OBJECTIVE: To assess the value of three-dimensional
      echocardiography (3DE) in predicting response to CRT. METHODS: Functional
      assessments and 3DE were performed in heart failure patients pre-CRT, 24 h post
      CRT and six to 12 months after CRT. The dyssynchrony index (DI) was calculated as
      the SD of the time to minimum volume in 16 left ventricle segments corrected by
      heart rate. Response to CRT was defined as functional improvement (alive at late
      follow-up with improvement by one New York Heart Association class) and a
      decrease in left ventricular end-systolic volume by 15% or greater at six to 12
      months follow-up. RESULTS: A total of 53 patients were enrolled. Average 3DE
      acquisition time was less than 5 min. Seventy-two per cent of patients showed
      functional improvement, while 43% showed functional and echocardiographic
      evidence of response. Baseline DI and the decrease in DI at 24 h were both
      correlated with reverse remodelling. Responders had higher baseline DI values
      compared with nonresponders (mean 16.8 versus 7.1, P<0.001), and showed a greater
      decrease in DI values at 24 h (mean decrease 7.9 versus 0.7, P<0.001). All
      responders had baseline DI values of greater than 10 (negative predictive value
      of 100%). A decrease in the DI value by more than 5 at 24 h in patients with a
      baseline DI of greater than 10 identified responders with a positive predictive
      value of 83%. CONCLUSIONS: 3DE may be valuable in predicting response to CRT. A
      baseline DI cut-off of greater than 10 in our patients excluded reverse
      remodelling to CRT. In addition, the decrease in DI at 24 h had a high positive
      predictive value for long-term response to CRT.

PMID- 21076721
TI  - Effect of different loading doses of atorvastatin on percutaneous coronary
      intervention for acute coronary syndromes.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI)-induced myocardial damage is
      associated with late cardiovascular events. Treatment with atorvastatin before
      PCI can reduce myocardial damage during the peri-PCI period. OBJECTIVES: To
      compare the safety and myocardial effects of different atorvastatin loading doses
      and dosing frequency before PCI in non-ST segment elevation acute coronary
      syndrome (NSTE-ACS) patients. METHODS: Eighty NSTE-ACS patients were randomly
      divided into four groups (20 patients per group). The control group was given 40
      mg atorvastatin each night. The three loading dose groups were treated the same
      as in the control group, but were given 80 mg atorvastatin 12 h before PCI
      (lowload group) in combination with 40 mg atorvastatin 2 h to 4 h before PCI (mid
      load group) or 60 mg atorvastatin 2 h to 4 h before PCI (high-load group). All
      patients underwent PCI within 48 h to 72 h of admission, and received 40 mg
      atorvastatin for at least one month after PCI. Changes in myocardial markers and
      highly sensitive C-reactive protein were analyzed. Patients were followed up for
      30 days to monitor the incidence of major adverse cardiac events (MACE). RESULTS:
      No deaths or revascularizations were recorded. The incidences of MACE differed
      significantly between the four groups (40%, 25%, 10% and 0% for the control, low
      load, mid-load and high-load groups, respectively; P<0.05). The incidence of MACE
      and cardiac troponin I level above the normal range, and post-PCI increases in
      creatine kinase-MB and highly sensitive C-reactive protein were significantly
      higher in the control group than in the high-load group (all P<0.007). The post
      PCI alanine aminotransferase levels in all four groups were significantly higher
      than the pre-PCI levels, but were within normal ranges. No myalgia or myasthenia
      was observed. CONCLUSION: The results of the present study show that short-term
      atorvastatin loading before PCI was well tolerated and had beneficial myocardial
      effects in patients with NSTE-ACS.

PMID- 21076722
TI  - Statins before stents: does an ounce of prevention improve outcomes?

PMID- 21076723
TI  - The cardiovascular effects of flaxseed and its omega-3 fatty acid, alpha
      linolenic acid.
AB  - Preventing the occurrence of cardiovascular disease (CVD) with nutritional
      interventions is a therapeutic strategy that may warrant greater research
      attention. The increased use of omega (&omega;)-3 fatty acids is a powerful
      example of one such nutritional strategy that may produce significant
      cardiovascular benefits. Marine food products have provided the traditional
      dietary sources of &omega;-3 fatty acids. Flaxseed is an alternative to marine
      products. It is one of the richest sources of the plant-based &omega;-3 fatty
      acid, alpha-linolenic acid (ALA). Based on the results of clinical trials,
      epidemiological investigations and experimental studies, ingestion of ALA has
      been suggested to have a positive impact on CVD. Because of its high ALA content,
      the use of flaxseed has been advocated to combat CVD. The purpose of the present
      review was to identify the known cardiovascular effects of flaxseed and ALA and,
      just as importantly, what is presently unknown.

PMID- 21076725
TI  - Dietary cholesterol and egg yolks: not for patients at risk of vascular disease.
AB  - A widespread misconception has been developing among the Canadian public and
      among physicians. It is increasingly believed that consumption of dietary
      cholesterol and egg yolks is harmless. There are good reasons for long- standing
      recommendations that dietary cholesterol should be limited to less than 200
      mg/day; a single large egg yolk contains approximately 275 mg of cholesterol
      (more than a day's worth of cholesterol). Although some studies showed no harm
      from consumption of eggs in healthy people, this outcome may have been due to
      lack of power to detect clinically relevant increases in a low-risk population.
      Moreover, the same studies showed that among participants who became diabetic
      during observation, consumption of one egg a day doubled their risk compared with
      less than one egg a week. Diet is not just about fasting cholesterol; it is
      mainly about the postprandial effects of cholesterol, saturated fats, oxidative
      stress and inflammation. A misplaced focus on fasting lipids obscures three key
      issues. Dietary cholesterol increases the susceptibility of low-density
      lipoprotein to oxidation, increases postprandial lipemia and potentiates the
      adverse effects of dietary saturated fat. Dietary cholesterol, including egg
      yolks, is harmful to the arteries. Patients at risk of cardiovascular disease
      should limit their intake of cholesterol. Stopping the consumption of egg yolks
      after a stroke or myocardial infarction would be like quitting smoking after a
      diagnosis of lung cancer: a necessary action, but late. The evidence presented in
      the current review suggests that the widespread perception among the public and
      health care professionals that dietary cholesterol is benign is misplaced, and
      that improved education is needed to correct this misconception.

PMID- 21076726
TI  - Single-chamber, rate-responsive pacemaker-mediated tachycardia.
AB  - The case of a patient with a unipolar VVIR, who developed a sensor-driven
      increased pacing rate at rest following pulse generator replacement, is
      presented. The cause was pectoral muscle stimulation, which triggered a sensor
      driven rate response in the supine position. The possible causes and management
      are discussed.

PMID- 21076727
TI  - Implantable cardioverter defibrillator: charge saver, not syncope saver!
AB  - In patients with an implantable cardioverter defibrillator, empirical
      antitachycardia pacing/burst pacing (ATP) is associated with a significantly
      decreased rate of appropriate shocks. The use of ATP as first-line therapy in
      ventricular tachycardia promotes less pain and better quality of life because the
      number of shocks is reduced. Additionally, battery longevity is substantially
      increased with this strategy. Based on this, device manufacturers have developed
      new algorithms to optimize the use of ATP and shocks in patients with an
      implantable cardioverter defibrillator. The present report describes a case in
      which the use of one of these new algorithms was associated with a significant
      delay in tachycardia termination and, consequently, led to syncope.

PMID- 21076728
TI  - Images in cardiology. Intracardiac pneumatic nails.

PMID- 21076729
TI  - Mining the polarization-dependence of nonlinear optical measurements.
AB  - The electromagnetic field strength present within the focal volume of a pulsed
      laser is routinely high enough to produce reasonably efficient nonlinear summing
      and mixing of optical frequencies. The polarization-dependence of the outgoing
      beam is a sensitive function of the polarization state(s) of the incident beam(s)
      and the structure, orientation, and symmetry of the sample. Mining this
      information hinges on two elements: (1) accurate and precise polarization
      dependent measurements, and (2) reliable modeling to relate the measured
      responses back to local structure and orientation. The central focus of this
      review is on the first step. Experimental strategies for precise and accurate
      nonlinear optical ellipsometry (NOE) polarization measurements are summarized for
      the most common and simplest case of second harmonic generation (SHG), or the
      frequency doubling of light, although extension to higher-order nonlinear optical
      interactions is straightforward in most cases.

PMID- 21076730
TI  - A general and mild domino approach to substituted 1-aminoindoles.
AB  - A versatile and efficient palladium catalyzed domino reaction leading to a broad
      range of substituted 1-aminoindoles has been developed. The title compounds were
      prepared from 2-halo-phenylacetylenes and simple hydrazines in good to excellent
      yields in just a few hours under mild conditions.

PMID- 21076731
TI  - Photodissociation of pyrrole-ammonia clusters by velocity map imaging: mechanism
      for the H-atom transfer reaction.
AB  - The photodissociation dynamics of pyrrole-ammonia clusters (PyH.(NH(3))(n), n = 2
      6) has been studied using a combination of velocity map imaging and non-resonant
      detection of the NH(4)(NH(3))(n-1) products. The excited state hydrogen-atom
      transfer mechanism (ESHT) is evidenced through delayed ionization and presents a
      threshold around 236.6 nm, in agreement with previous reports. A high resolution
      determination of the kinetic energy distributions (KEDs) of the products reveals
      slow (~0.15 eV) and structured distributions for all the ammonia cluster masses
      studied. The low values of the measured kinetic energy rule out the existence of
      a long-lived intermediate state, as it has been proposed previously. Instead, a
      direct N-H bond rupture, in the fashion of the photodissociation of bare pyrrole,
      is proposed. This assumption is supported by a careful analysis of the structure
      of the measured KEDs in terms of a discrete vibrational activity of the pyrrolyl
      co-fragment.

PMID- 21076732
TI  - In situ synthesis of high-loading Li4Ti5O12-graphene hybrid nanostructures for
      high rate lithium ion batteries.
AB  - Nanocrystalline Li4Ti5O12 grown on conducting graphene nanosheets (GNS) with good
      crystallinity was investigated as an advanced lithium-ion battery anode material
      for potential large-scale applications. This hybrid anode nanostructure material
      showed ultrahigh rate capability and good cycling properties at high rates.

PMID- 21076733
TI  - New Cu(II) complexes based on the hydroxo-bridged dinuclear [Cu(OH)2Cu] units:
      step-like di- and trimerizations of [Cu(OH)2Cu] units.
AB  - Four new Cu(II) complexes
      {[Cu(4)(bpy)(4)(OH)(4)(H(2)O)(2)]}(NO(3))(2)(C(7)H(5)O(2))(2).6H(2)O 1,
      {[Cu(4)(bpy)(4)(OH)(4)(H(2)O)(2)]}(NO(3))(2)(C(5)H(6)O(4)).8H(2)O 2,
      {[Cu(4)(bpy)(4)(OH)(4)(H(2)O)(2)]}(C(5)H(6)O(4))(2).16H(2)O 3 and
      {[Cu(6)(bpy)(6)(OH)(6)(H(2)O)(2)]}(C(8)H(7)O(2))(6).12H(2)O 4 were synthesized
      (bpy = 2,2'-bipyridine, H(2)(C(5)H(6)O(4)) = glutaric acid, H(C(7)H(5)O(2)) =
      benzoic acid, H(C(8)H(7)O(2)) = phenyl acetic acid). The building units in 1-3
      are the tetranuclear [Cu(4)(bpy)(4)(H(2)O)(2)(MU(2)-OH)(2)(MU(3)-OH)(2)](4+)
      complex cations, and in 4 the hexanuclear [Cu(6)(bpy)(6)(H(2)O)(2)(MU(2)
      OH)(2)(MU(3)-OH)(4)](6+) complex cations, respectively. The tetra- and
      hexanuclear cluster cores [Cu(4)(MU(2)-OH)(2)(MU(3)-OH)(2)] and [Cu(6)(MU(2)
      OH)(2)(MU(3)-OH)(4)] in the complex cations could be viewed as from step-like di-
      and trimerization of the well-known hydroxo-bridged dinuclear [Cu(2)(MU(2)
      OH)(2)] entities via the out-of-plane Cu-O(H) bonds. The complex cations are
      supramolecularly assembled into (4,4) topological networks via intercationic pipi
      stacking interactions. The counteranions and lattice H(2)O molecules are
      sandwiched between the 2D cationic networks to form hydrogen-bonded networks in 1
      3, while the phenyl acetate anions and the lattice H(2)O molecules generate 3D
      hydrogen-bonded anionic framework to interpenetrate with the (4,4) topological
      cationic networks with the hexanuclear complex cations in the channels. The
      ferromagnetic coupling between Cu(II) ions in the [Cu(4)(MU(2)-OH)(2)(MU(3)
      OH)(2)] cores of 1-3 is significantly stronger via equatorial-equatorial OH(-)
      bridges than via equatorial-apical ones. The outer and the central [Cu(2)(OH)(2)]
      unit within the [Cu(6)(MU(2)-OH)(2)(MU(3)-OH)(4)] cluster cores in 4 exhibit weak
      ferromagnetic and antiferromagnetic interactions, respectively. Results about
      i.r. spectra, thermal and elemental analyses are presented.

PMID- 21076734
TI  - Affinity of hydroxyapatite (001) and (010) surfaces to formic and alendronic
      acids: a quantum-mechanical and infrared study.
AB  - The affinity of the (001) and of the water reacted (010)WR hydroxyapatite
      surfaces towards formic and alendronic acids is studied with density functional
      theory (PBE functional) using periodic boundary conditions based on Gaussian
      basis set. Structures, energetic of the adsorption and vibrational features of
      the adsorbates are computed in order to understand at the atomic level both the
      cariogenic processes (for the formic acid) and the features of anti-osteoporosis
      drugs (for the alendronic acid). For both molecules the interaction energy is
      very high on an absolute scale, and for all examined cases, it is higher on the
      (010)WR HA surface than on the (001) one. For the latter, a number of cases by
      which the acidic proton of the adsorbate is transferred to the HA surface are
      also characterized. For the formic acid case, experimental infrared spectra are
      also measured and the position and nature of the C=O stretching bands have been
      found to be in excellent agreement with the quantum mechanical simulations. For
      alendronic acid IR experiments are still not available and the present predicted
      infrared spectra will be useful as a guide to interpret future experimental
      studies.

PMID- 21076724
TI  - Prevalence of dyslipidemia in statin-treated patients in Canada: results of the
      DYSlipidemia International Study (DYSIS).
AB  - BACKGROUND: Despite clear guideline recommendations, there is a growing body of
      evidence that there is suboptimal use of lipid-lowering treatment in Canadians.
      OBJECTIVE: To assess the prevalence and types of persistent lipid abnormalities
      in Canadian patients receiving statin therapy. METHODS: The present cross
      sectional study recruited 2436 outpatients 45 years of age or older who were
      treated with statins by 232 physicians from 10 provinces; all underwent clinical
      examination and had their latest fasting lipid values while on statin therapy
      recorded. RESULTS: The median patient age was 66 years (interquartile range [IQR]
      58 to 74 years), 60% were men and 80% were in the high 10-year risk category. The
      median low-density lipoprotein cholesterol level was 2.0 mmol/L (IQR 1.6 mmol/L
      to 2.5 mmol/L) and the median total cholesterol/high-density lipoprotein
      cholesterol ratio was 3.4 mmol/L (IQR 2.8 mmol/L to 4.1 mmol/L). However, based
      on the 2006 Canadian Cardiovascular Society recommendations, 37% of all patients
      did not have a low-density lipoprotein cholesterol level at goal or intervention
      target level, including 45% of high-risk category patients. The majority of
      patients received atorvastatin (50%) or rosuvastatin (37%) but primarily at low
      to-medium doses, and a minority (14%) received additional lipid-modifying
      therapies. CONCLUSIONS: The present observational study highlights the need for
      more intensive treatment of lipid abnormalities, particularly among high-risk
      patients. Recognizing several important limitations related to the observational
      nature of the study, the findings suggest the possibility that, in addition to
      optimizing adherence, there remains an important need to titrate current statin
      therapy to higher doses and potentially use a combination of lipid-modifying
      treatments (once the statin dose has been truly maximized) to further bridge the
      gap between evidence-based medicine and current Canadian practice.

PMID- 21076735
TI  - [(C3H4N2)2Au]Cl--a bis protic gold(I)-NHC.
AB  - The gold(I) bis-NHC (NHC = imidazol-2-ylidene) parent compound was synthesised in
      high yield by a three step reaction starting from imidazole. The compound is
      highly water soluble and stable in concentrated hydrochloric acid.

PMID- 21076736
TI  - Sensitizer molecular structure-device efficiency relationship in dye sensitized
      solar cells.
AB  - In the Dye Sensitized Solar Cell (DSSC) the dye sensitizer carries out the light
      harvesting function and is therefore crucial in determining overall cell
      efficiency. In addition, the dye sensitizer can influence many of the key
      electron transfer processes occurring at the TiO(2)/dye/electrolyte interface
      which also determine efficiency. Dye structure can influence and drive forward
      electron injection into the conduction band of the TiO(2). Conversely, dye
      structure can help retard loss electron transfer processes such as charge
      recombination of injected electrons in the TiO(2) with dye cations and also
      recombination of these electrons with the electrolyte. Therefore tuning dye
      sensitizer light absorbing properties and control of the aforementioned electron
      transfer processes through structural design of the dye sensitizer is an
      important avenue through which optimization of DSSC efficiency should be pursued.
      In this critical review the latest work focusing on the design of dyes for
      efficient DSSCs is revised (111 references).

PMID- 21076737
TI  - One-component bimetallic aluminium(salen)-based catalysts for cyclic carbonate
      synthesis and their immobilization.
AB  - The development of one-component, bimetallic MU-oxoaluminium(salen) complexes as
      highly active catalysts for the synthesis of cyclic carbonates from terminal
      epoxides is described. The resulting homogeneous catalysts are used in batch
      reactions at room temperature and one atmosphere pressure. The catalysts have
      also been immobilized onto various support materials and used in either batch
      reactions or gas-phase flow reactions with ethylene and propylene oxides.
      Catalyst lifetime, deactivation and reactivation have been studied in both batch
      and flow reactions, and it has been shown that of the impurities present in power
      station flue gas, only sulfur trioxide deactivates the catalyst and at the
      concentrations of sulfur trioxide present in flue gas, this deactivation would
      require more than one years exposure of the catalyst to flue gas.

PMID- 21076738
TI  - A kinetic study on the conversion of cis-2-butene with deuterium on a Pd/Fe3O4
      model catalyst.
AB  - The conversion of cis-2-butene with deuterium over a well-defined Pd/Fe(3)O(4)
      model catalyst was studied by isothermal pulsed molecular beam (MB) experiments
      under ultra high vacuum conditions. This study focuses on the processes related
      to dissociative hydrogen adsorption and diffusion into the subsurface of Pd
      nanoparticles and their influence on the activity and selectivity toward
      competing cis-trans isomerization and hydrogenation pathways. The reactivity was
      studied both under steady state conditions and in the transient regime, in which
      the reaction takes place on a D-saturated catalyst, over a large range of
      reactant pressures and reaction temperatures. We show that large olefin coverages
      negatively affect the abundance of D species, as indicated by a reduction of both
      reaction rates under steady state conditions as compared to the transient
      reactivity on the catalyst pre-saturated with D(2). Limitations in D availability
      during the steady state lead to a very weak dependence of both reaction rates on
      the olefin pressure. In contrast, when the surface is initially saturated with D,
      the transient reaction rates of both pathways exhibit positive kinetic orders on
      the butene pressure. Cis-trans isomerization and hydrogenation show kinetic
      orders of +0.7 and +1.0 on the D(2) pressure, respectively. Increasing
      availability of D noticeably shifts the selectivity toward hydrogenation. These
      observations together with the analysis of the transient reaction behavior
      suggest that the activity and selectivity of the catalyst is strongly controlled
      by its ability to build up and maintain a sufficiently high concentration of D
      species under reaction conditions. The temperature dependence of the reaction
      rates indicates that higher activation energies are required for the
      hydrogenation pathway than for the cis-trans isomerization pathway, implying that
      different rate limiting steps are involved in the competing reactions.

PMID- 21076739
TI  - Conversion of tetrahedral to octahedral structures upon solvent coordination:
      studies on the M[(OPPh2)(SePPh2)N]2 (M = Co, Ni) and [Ni{(OPPh2)(EPPh2)N}2(dmf)2]
      (E = S, Se) complexes.
AB  - The synthesis of the M[(OPPh(2))(SePPh(2))N](2), M = Co (1), Ni (2) complexes was
      accomplished by metathetical reactions between the corresponding M(II) salts and
      the deprotonated form of the dichalcogenated imidodiphosphinato ligand
      [(OPPh(2))(SePPh(2))N](-). X-Ray crystallography revealed a pseudo-tetrahedral
      MO(2)Se(2) coordination sphere, owing to the asymmetric (O,Se) nature of the
      chelating ligand. Slow diffusion of the coordinating solvent dimethylformamide
      into dichloromethane solutions of Ni[(OPPh(2))(SPPh(2))N](2) or 2, afforded the
      pseudo-octahedral trans-[Ni{(OPPh(2))(EPPh(2))N}(2)(dmf)(2)], E = S (3), Se (4)
      complexes, respectively. UV-vis spectra provided evidence that, in solution,
      complexes 3 and 4 revert to the corresponding pseudo-tetrahedral complexes, most
      likely due to the removal of the dmf molecules from the coordination sphere. The
      IR spectra of all complexes reflect the structural features observed by X-ray
      crystallography. The magnetic properties of the S = 3/2 complex 1, as well as the
      S = 1 complexes 2, 3 and 4, were extensively studied, and the magnitude of their
      g and zero-field splitting D parameters was estimated. The reported structures
      establish a structural transformation of tetrahedral to octahedral geometry of
      Ni(II) complexes bearing asymmetric imidodiphosphinate ligands, upon
      recrystallization from coordinating solvents. The structural correlations between
      the Ni(II) coordination spheres are aided by DFT and ab initio multi
      configuration MCSCF calculations, which investigate the corresponding
      interconversion pathways. In addition, the calculations provide descriptions of
      the bonding interactions in the octahedral Ni(II) complexes, as well as
      predictions of their D values.

PMID- 21076740
TI  - Reactivity of the 16e Cp*Co half-sandwich complex containing a chelating 1,2
      dicarba-closo-dodecaborane-1,2-dithiolate ligand towards alkynes.
AB  - The 16e half-sandwich complex Cp*Co(S(2)C(2)B(10)H(10))(1, Cp* =
      pentamethylcyclopentadienyl) reacts with N-1-naphthylpropargylamide to afford two
      18e complexes (2) and (3). 2 is a 1 : 1 adduct containing a four-membered
      metallacycle. In 3 the alkyne is twofold inserted into one Co-S bond in a head
      head mode. Reactions of 1 with 1-(2-furyl)-2-propyn-1-one and 1-ferrocenyl-2
      propyn-1-one lead to two types of alkyne twofold inserted products (4)/(5) and
      (6)/(7), respectively. The reaction of 1 with phenylacetylene gives rise to the
      sole complex (8) of the same structural type as 3, 4 and 6, whereas the reaction
      of 1 with dimethyl acetylene dicarboxylate affords the sole 1 : 1 adduct (9).
      Complexes 2-9 have been characterized by IR, NMR, elemental analysis and mass
      spectrometry, and 3-9 have also been determined by single-crystal X-ray
      diffraction analysis.

PMID- 21076741
TI  - Synthesis of a novel unsymmetrical Zn(II) phthalocyanine bearing a phenyl ethynyl
      moiety as sensitizer for dye-sensitized solar cells.
AB  - A new unsymmetrical zinc phthalocyanine sensitizer has been synthesised. The
      anchoring of the molecule to nanocrystalline TiO(2) films is realised by a
      carboxylic group connected to a phenyl ethynyl moiety. Density Functional Theory
      (DFT) calculations show significant and positive effects of such a
      functionalization. Electron injection into the semiconductor and photocurrent
      generation in DSSC are also presented.

PMID- 21076742
TI  - Sequestration of naphthenic acids from aqueous solution using beta-cyclodextrin
      based polyurethanes.
AB  - The sorption characteristics of naphthenic acids (NAs) in their anion form with
      beta-cyclodextrin (beta-CD) based polyurethanes, as sorbents, from aqueous
      solutions that simulate the conditions of oil sands process water (OSPW) are
      presented. The copolymer sorbents were synthesized at various beta
      CD:diisocyanate monomer mole ratios (e.g., 1:1, 1:2, and 1:3) with diisocyanates
      of variable molecular size and degree of unsaturation. The equilibrium sorption
      properties of the copolymer sorbents were characterized using sorption isotherms
      in aqueous solution at pH 9.00 with electrospray ionization mass spectrometry to
      monitor the equilibrium unbound fraction of anionic NAs in the aqueous phase. The
      copolymer sorbents were characterized in the solid state using (13)C CP-MAS NMR
      spectroscopy, IR spectroscopy and elemental analysis. The sorption results of the
      copolymer sorbents with anion forms of NAs in solution were compared with a
      commercially available carbonaceous standard: granular activated carbon (GAC).
      The monolayer sorption capacities of the sorbents (Q(m)) were obtained from
      either the Langmuir or the Sips isotherm model used to characterize the sorption
      characteristics of each copolymer sorbent. The estimated sorption capacity for
      GAC was 142 mg NAs per g sorbent whereas the polymeric materials ranged from 0-75
      mg NAs per g sorbent over the experimental conditions investigated. In general,
      significant differences in the sorption capacities between GAC and the copolymer
      sorbents were related to the differences in the accessible surface areas and pore
      structure characteristics of the sorbents. The Sips parameter (K(eq)) for GAC and
      the copolymer materials reveal differences in the relative binding affinity of
      NAs to the sorbent framework in accordance with the synthetic ratios and the
      value of Q(m). The diisocyanate linker plays a secondary role in the sorption
      mechanism, whereas the beta-CD macrocycle in the copolymer framework is the main
      sorption site for NAs because of the formation of inclusion complexes with beta
      CD.

PMID- 21076743
TI  - Photoreaction pathways for the anticancer complex trans,trans,trans
      [Pt(N3)2(OH)2(NH3)2].
AB  - The photodecomposition of the anticancer complex trans,trans,trans
      [Pt(N(3))(2)(OH)(2)(NH(3))(2)] in acidic aqueous solution, as well as in
      phosphate-buffered saline (PBS), induced by UVA light (centred at lambda = 365
      nm) has been studied by multinuclear NMR spectroscopy. We show that the
      photoreaction pathway in PBS, which involves azide release, differs from that in
      acidic aqueous conditions, under which N(2) is a major product. In both cases, a
      number of trans-{N-Pt(II/IV)-NH(3)} species were also observed as photoproducts,
      as well as the evolution of O(2) and release of free ammonia with a subsequent
      increase in pH. The results from this study illustrate that photoinduced
      reactions of Pt(IV)-diazido derivatives can lead to novel reaction pathways, and
      therefore potentially to new cytotoxic mechanisms in cancer cells.

PMID- 21076744
TI  - Microwave-assisted synthesis of hydrophilic BaYF5:Tb/Ce,Tb green fluorescent
      colloid nanocrystals.
AB  - Hydrophilic Ce, Tb doped BaYF(5) nanocrystals with uniform size were synthesized
      by a microwave-assisted route. The synthesized nanocrystals can be well dispersed
      in hydrophilic solutions (DMSO, DMF, EG, H(2)O). This synthesis procedure
      represents a less time consuming method, with high product yield and without
      using any assistant or/and template reagents, which may be expected to be a
      general method for rapid synthesis of other hydrophilic RE doped fluoride
      fluorescent nanocrystals. The Ce(3+), Tb(3+) codoped BaYF(5) nanocrystals show
      bright green fluorescence emission. The Ce(3+) acts as an effective energy
      transfer medium and the emission at the high (5)D(3) energy level of Tb is
      enhanced in this host material.

PMID- 21076745
TI  - CO2 capture by hydrocarbon surfactant liquids.
AB  - Here we found that CO(2) has high solubility in low-cost hydrocarbon surfactant
      liquids.

PMID- 21076746
TI  - Recent applications of ring-closing metathesis in the synthesis of lactams and
      macrolactams.
AB  - Lactams are an important class of compounds owing to their presence in numerous
      biologically active molecules of natural and unnatural nature. They are also
      highly versatile intermediates that can be elaborated into interesting compounds
      for potential use in organic and medicinal chemistry endeavors. In this feature
      article, the reader will be given a background to olefin metathesis followed by
      concise discussions (with selected examples) to report recent applications of
      ring-closing metathesis to form lactams and macrolactams from acyclic diene
      precursors, an area which continues to deposit attractive applications in the
      chemical literature en route or in the final step to the target molecules.

PMID- 21076747
TI  - A theoretical investigation of inositol 1,3,4,5-tetrakisphosphate.
AB  - This paper describes the parameterization of inositol 1,3,4,5-tetrakisphosphate
      [Ins(1,3,4,5)P(4)] for use in molecular dynamics (MD) simulations. For this
      theoretical investigation, eleven isomers of Ins(1,3,4,5)P(4), with different
      levels and arrangements of protonation, have been considered. Herein we report
      accurate quantum mechanics (QM) calculations offering a detailed description of
      the energetic and structural properties of the Ins(1,3,4,5)P(4) isomers and
      subsequent development of parameters for these isomers for application in the
      AMBER force field. QM calculations were employed to geometry optimize the
      Ins(1,3,4,5)P(4) isomers, using the DFT-B3LYP level of theory in gas phase. In
      subsequent steps, charge parameters were generated for each isomer. These charge
      parameters, plus assigned atom-types from the AMBER ff99SB force field, were then
      applied to the optimized isomers for energy minimization in AMBER. The quality of
      the parameters was evaluated by comparing the structural, energetic and
      spectroscopic properties of the Ins(1,3,4,5)P(4) isomers between the QM geometry
      optimization stage, from which the parameters were generated, and the energy
      minimization stage, in which the parameters were applied. The results were shown
      to be in strong qualitative agreement between these stages, suggesting good
      quality parameters have been obtained. Additionally, adaptations to the gas phase
      protocol, investigating the use of the MP2 method for the geometry optimization
      stage and GAFF atom-types for the energy minimization stage, were tested. These
      results confirmed the initial protocol applied was the most appropriate.
      Calculations for the Ins(1,3,4,5)P(4) isomers were also carried out in the
      presence of implicit solvent, allowing comparison and validation of the
      theoretical calculations with experimental data. The computed energetic
      properties of the Ins(1,3,4,5)P(4) isomers were assessed against their
      experimental probabilities based on (31)P-NMR titration data. The computational
      and experimental results were shown to be in strong agreement, with the lower
      energy isomers corresponding to those more probable. This paper reports a clearly
      defined algorithmic approach to generate parameters for the highly charged
      Ins(1,3,4,5)P(4) ligand, permitting their use in future MD studies.

PMID- 21076748
TI  - Redox chemistry in thin layers of organometallic complexes prepared using ion
      soft landing.
AB  - Soft landing (SL) of mass-selected ions is used to transfer catalytically-active
      metal complexes complete with organic ligands from the gas phase onto an inert
      surface. This is part of an effort to prepare materials with defined active sites
      and thus achieve molecular design of surfaces in a highly controlled way.
      Solution-phase electrochemical studies have shown that V(IV)O(salen) reacts in
      the presence of acid to form V(V)O(salen)(+) and the deoxygenated
      V(III)(salen)(+) complex-a key intermediate in the four electron reduction of
      O(2) by vanadium-salen. In this work, the V(V)O(salen)(+) and [Ni(II)(salen) +
      H](+) complexes were generated by electrospray ionization and mass-selected
      before being deposited onto an inert fluorinated self-assembled monolayer (FSAM)
      surface on gold. A time dependence study after ion deposition showed loss of O
      from V(V)O(salen)(+) forming V(III)(salen)(+) over a four-day period, indicating
      a slow interfacial reduction process. Similar results were obtained when other
      protonated molecules were co-deposited with V(V)O(salen)(+) on the FSAM surface.
      In all these experiments oxidation of the V(III)(salen)(+) product occurred upon
      exposure to oxygen or to air. The cyclic regeneration of V(V)O(salen)(+) upon
      exposure to molecular oxygen and its subsequent reduction to V(III)(salen)(+) in
      vacuum completes the catalytic cycle of O(2) reduction by the immobilized
      vanadium-salen species. Moreover, our results represent the first evidence of
      formation of reactive organometallic complexes on substrates in the absence of
      solvent. Remarkably, deoxygenation of the oxo-vanadium complex, previously
      observed only in highly acidic non-aqueous solvents, occurs on the surface in the
      UHV environment using an acid which is deposited into the inert monolayer. This
      acid can be a protonated metal complex, e.g. [Ni(II)(salen) + H](+), or an
      organic acid such as protonated diaminododecane.

PMID- 21076749
TI  - Enhanced stability of G-quadruplexes from conformationally constrained aep-PNA
      backbone.
AB  - Nucleic (DNA) acids having contiguous stretch of G sequence form quadruplex
      structure, which is very critical to control cell division. Recently the
      existence of G-quadruplex in RNA is also reported in presence of monovalent metal
      ion. PNA is a promising DNA analogue which binds strongly to DNA to form PNA:DNA
      duplex or PNA(2):DNA triplex. PNA also forms quadruplexes such G-quadruplex and i
      motif in G and C-rich sequences respectively. aep-PNA containing a prolyl ring is
      one of several PNA analogues that provide rigidity and chirality in backbone and
      has binding affinity to natural DNA which is higher than that of PNA. Here we
      examine the ability of aep-PNA-G to form a quadruplex by UV, CD and mass
      spectroscopic techniques.

PMID- 21076750
TI  - A butadiyne-linked diruthenium molecular wire self-assembled on a gold electrode
      surface.
AB  - A 1,3-butadiyne-linked diruthenium complex 4 is successfully brought onto the
      gold surface in a lying flat mode to form self-assembled monolayers (SAMs)
      showing reversible multiple redox behaviors on the electrode surface. The
      diruthenium species with different oxidation states, particularly the
      Ru(2)(III,III) state which is unstable and impossible to isolate from the
      solution, can be detected by in situ IR spectroscopy.

PMID- 21076752
TI  - Surfactant-modified MFI nanosheets: a high capacity anion-exchanger.
AB  - Surfactant-Modified MFI-Zeolite Nanosheets (SMZN) were used for the first time as
      anion-exchangers, in the case of nitrate ion removal. The SMZN material is
      characterized by high anionic exchange capacity and removal efficiency compared
      to classical SMZ prepared from clinoptilolite. The SMZN material is easily
      regenerated and could be probably employed to remove other anionic pollutants.

PMID- 21076751
TI  - Tailored coordination nanoparticles: assessing the magnetic single-domain
      critical size.
AB  - Negatively charged nanocrystals of the magnetic coordination network
      CsNiCr(CN)(6) were prepared in water through a seed-mediated growth with a few
      atomic layers accuracy and final sizes tailored from 6 to 30 nm. A lower limit of
      the magnetic single-domain critical size was determined to be around 15 nm
      possessing a blocking temperature above 20 K.

PMID- 21076753
TI  - Mn3O4 catalyzed growth of polycrystalline Pt nanoparticles and single crystalline
      Pt nanorods with high index facets.
AB  - Rarely-observed polycrystalline twinned Pt nanoparticles (NPs) and length
      controlled Pt nanorods (NRs) with exposed high index facets were prepared through
      an unexpectedly catalytic growth approach from low-cost Mn(3)O(4) NPs. The as
      prepared Pt NRs exhibit higher catalytic activity and better stability for the
      oxidization of methanol than commercial Pt/C catalysts, indicating the promise of
      this catalyst in direct methanol fuel cells.

PMID- 21076754
TI  - Enhanced chemiluminescence detection of thrombin based on cerium oxide
      nanoparticles.
AB  - Polyacrylic acid coated nanoceria (PNCs) were found to greatly enhance the
      chemiluminescence (CL) intensity of the luminol-H(2)O(2) system, and by virtue of
      the catalytic ability of PNCs, a sensitive and specific sandwich assay for human
      alpha-thrombin was developed.

PMID- 21076755
TI  - Intramolecular iodoetherification of ene or diene ketals: facile synthesis of
      spiroketals.
AB  - A novel and rapid approach to chiral mono- or di-substituted spiroketals based on
      remote asymmetric induction by intramolecular iodoetherification of ene or diene
      ketals has been developed. This strategy concisely offers 5,5- and 5,6
      spiroketals including the natural insect pheromone of the wasp.

PMID- 21076756
TI  - Microfluidics analysis of red blood cell membrane viscoelasticity.
AB  - In this work, a microfluidic system to investigate the flow behavior of red blood
      cells in a microcirculation-mimicking network of PDMS microchannels with
      thickness comparable to cell size is presented. We provide the first quantitative
      description of cell velocity and shape as a function of the applied pressure drop
      in such devices. Based on these results, a novel methodology to measure cell
      membrane viscoelastic properties in converging/diverging flow is developed, and
      the results are in good agreement with data from the literature. In particular,
      in the diverging channel the effect of RBC surface viscosity is dominant with
      respect to shear elasticity. Possible applications include measurements of cell
      deformability in pathological samples, where reliable methods are still lacking.

PMID- 21076757
TI  - Interactions in the native state of monellin, which play a protective role
      against aggregation.
AB  - A series of recent studies have provided initial evidence about the role of
      specific intra-molecular interactions in maintaining proteins in their soluble
      state and in protecting them from aggregation. Here we show that the amino acid
      sequence of the protein monellin contains two aggregation-prone regions that are
      prevented from initiating aggregation by multiple non-covalent interactions that
      favor their burial within the folded state of the protein. By investigating the
      behavior of single-chain monellin and a series of five of its mutational variants
      using a variety of biochemical, biophysical and computational techniques, we
      found that weakening of the non-covalent interaction that stabilizes the native
      state of the protein leads to an enhanced aggregation propensity. The lag time
      for fibrillation was found to correlate with the apparent midpoint of thermal
      denaturation for the series of mutational variants, thus showing that a reduced
      thermal stability is associated with an increased aggregation tendency. We
      rationalize these findings by showing that the increase in the aggregation
      propensity upon mutation can be predicted in a quantitative manner through the
      increase in the exposure to solvent of the amyloidogenic regions of the sequence
      caused by the destabilization of the native state. Our findings, which are
      further discussed in terms of the structure of monellin and the perturbation by
      the amino acid substitutions of the contact surface between the two subdomains
      that compose the folded state of monellin, provide a detailed description of the
      specific intra-molecular interactions that prevent aggregation by stabilizing the
      native state of a protein.

PMID- 21076758
TI  - Reactions between Grignard reagents and heterocyclic N-oxides: stereoselective
      synthesis of substituted pyridines, piperidines, and piperazines.
AB  - In this perspective we discuss the recent developments of stereoselective
      synthesis of substituted pyridines, piperidines, and piperazines from cheap and
      commercially readily available starting materials. Pyridine N-oxides and pyrazine
      N-oxides are reacted with alkyl, aryl, alkynyl and vinyl Grignard reagents to
      give a diverse set of heterocycles in high yields. Optically active substituted
      piperazines are obtained by an asymmetric reaction from pyrazine N-oxides using
      sparteine as chiral ligand. In addition, a stereoselective synthesis of dienal
      oximes from the reaction between pyridine N-oxides and Grignard reagents is
      presented, which results in a useful intermediate for the synthesis of a diverse
      set of compounds.

PMID- 21076759
TI  - A radical pathway to synthesise Mo and W dithiolene complexes.
AB  - A new method has been developed to synthesise bis eta(5)-cyclopentadienyl
      dithiolene complexes of molybdenum and tungsten. This procedure involves the in
      situ thermolysis of the azo compounds, 2,2'-azobisisobutyronitrile (AIBN) or 1,1'
      azobiscyclohexanecarbonitrile (ACCN) (R'(2)N(2), R' = CMe(2)CN or C(6)H(10)CN,
      respectively), which initiates a reaction between [Cp(2)M(S(4))] (M = Mo or W)
      and an alkyne (HC(2)R, R = Ph, 2-pyridyl or 2-quinoxalinyl) and produce the
      corresponding [Cp(2)M(S(2)C(2)RR')] compound.

PMID- 21076760
TI  - Control of ZnO morphologies on carbon nanotube electrodes and electrocatalytic
      characteristics toward hydrazine.
AB  - We controlled the morphologies of zinc oxide (ZnO) nanostructures on single
      walled carbon nanotube electrodes by an electrochemical deposition method and
      investigated the dependence of the electrocatalytic characteristics toward
      hydrazine on the different morphologies. ZnO nanorods provided high
      electrocatalytic activity with unique electrochemical behaviours, associated with
      the H(+) ion generated by the electro-oxidation of hydrazine.

PMID- 21076761
TI  - Heteroleptic N6 coordinated ruthenium(II) complexes as building blocks for the
      formation of discrete Ru2Ag2 complexes.
AB  - A heteroleptic N(6) coordinated Ru(II) complex acts as a building block for a
      discrete tetranuclear mixed metal Ru(II)(2)Ag(I)(2) coordination compound; both
      complexes have been structurally characterised by X-ray crystallography.

PMID- 21076762
TI  - A switchable fluorescent quantum dot probe based on aggregation/disaggregation
      mechanism.
AB  - Here we report a facile switchable fluorescent QD probe for F(-) ions, which is
      based on the hydrogen bonding-driven aggregation and the analyte-triggered
      disaggregation.

PMID- 21076763
TI  - An ionic porous coordination framework exhibiting high CO2 affinity and CO2/CH4
      selectivity.
AB  - An ionic porous coordination polymer possessing partially exposed uncoordinated
      nitrogens exhibits strong interaction with CO(2) and high CO(2)/CH(4)
      selectivity, and the adsorption mechanism is illustrated by the structure of its
      CO(2)-loaded single-crystal.

PMID- 21076764
TI  - Nickel based electrocatalysts for oxygen evolution in high current density,
      alkaline water electrolysers.
AB  - A number of nickel based materials are investigated as potential oxygen evolution
      catalysts under conditions close to those met in modern, high current density
      alkaline water electrolysers. Microelectrodes are used to avoid distortion of
      voltammetric data by IR drop even at the high current densities employed in such
      water electrolysers. High surface area nickel metal oxides prepared by cathodic
      deposition and mixed oxides prepared by thermal methods are considered. A mixed
      Ni/Fe oxide is the preferred electrocatalyst. The influence of hydroxide ion
      concentration and temperature on the voltammetry is defined. Preliminary
      stability tests in a zero gap cell with an OH(-) conducting membrane show no
      significant increase in overpotential during 10 days operation in 4 M NaOH
      electrolyte at a current density of 1 A cm(-2) at 333 K.

PMID- 21076765
TI  - Defocus image contrast in hexagonally-ordered mesoporous material.
AB  - A transmission electron microscope was used to characterize a powder form of
      hexagonally-ordered mesoporous silica material. The structural symmetry built
      into this amorphous material allowed one to obtain three characteristic images,
      i.e. a hexagonal honey-comb structure and wide/narrow parallel lines. These
      images were found to originate primarily from phase contrast, which changed
      sensitively with defocusing. To further understand the contrast behaviour of
      these images, an analytical form of the defocus contrast theory was developed and
      applied to the simulation of the characteristic wide/narrow parallel line images.
      The simulation was found to be in good qualitative agreement with experiments,
      where changes in focus conditions and specimen thickness were predicted to alter
      the contrast in the resulting parallel-line type images.

PMID- 21076766
TI  - A facile approach for quantifying the density of defects (edge plane sites) of
      carbon nanomaterials and related structures.
AB  - A facile methodology based on cyclic voltammetry is presented allowing the
      density of defects, viz edge plane like-sites/defects of carbon nanomaterials to
      be readily quantified. The approach is based on the construction of carbon
      nanomaterial paste electrodes which is measured using cyclic voltammetry and a
      standard electrochemical redox probe. This protocol allows a quantitative
      relationship between the heterogeneous electron-transfer rate and the density of
      defects to be readily determined and also provides researchers with a methodology
      to quantify the density of defects for comparative purposes.

PMID- 21076767
TI  - Does covalency really increase across the 5f series? A comparison of molecular
      orbital, natural population, spin and electron density analyses of AnCp3 (An = Th
      Cm; Cp = eta(5)-C5H5).
AB  - The title compounds are studied with scalar relativistic, gradient-corrected
      (PBE) and hybrid (PBE0) density functional theory. The metal-Cp centroid
      distances shorten from ThCp(3) to NpCp(3), but lengthen again from PuCp(3) to
      CmCp(3). Examination of the valence molecular orbital structures reveals that the
      highest-lying Cp pi(2,3)-based orbitals transform as 1e + 2e + 1a(1) + 1a(2).
      Above these levels come the predominantly metal-based 5f orbitals, which
      stabilise across the actinide series such that in CmCp(3) the 5f manifold is at
      more negative energy than the Cp pi(2,3)-based levels. Mulliken population
      analysis shows metal d orbital participation in the e symmetry Cp pi(2,3)-based
      orbitals. Metal 5f character is found in the 1a(1) and 1a(2) levels, and this
      contribution increases significantly from ThCp(3) to AmCp(3). This is in
      agreement with the metal spin densities, which are enhanced above their formal
      value in NpCp(3), PuCp(3) and especially AmCp(3) with both PBE and PBE0. However,
      atoms-in-molecules analysis of the electron densities indicates that the An-Cp
      bonding is very ionic, increasingly so as the actinide becomes heavier. It is
      concluded that the large metal orbital contributions to the Cp pi(2,3)-based
      levels, and enhanced metal spin densities toward the middle of the actinide
      series arise from a coincidental energy match of metal and ligand orbitals, and
      do not reflect genuinely increased covalency (in the sense of appreciable overlap
      between metal and ligand levels and a build up of electron density in the region
      between the actinide and carbon nuclei).

PMID- 21076768
TI  - Linear or cross-shaped di(cyclopentadienyltitanium) compounds with aryl or
      heteroaryl spacers.
AB  - The preparation of hexamethylated and hexabenzylated arylene or heteroarylene
      bridged dinuclear di(cyclopentadienyltitanium) compounds from the reaction of the
      corresponding hexachlorides with methyllithium or benzylmagnesium chloride is
      described. The spacers between the cyclopentadienyl rings consist of one, two or
      three phenylene groups, a dioctyloxyphenylene group or a 2,2'-bithienylene group.
      The corresponding hexachlorides and hexaisopropoxides have also been prepared.

PMID- 21076769
TI  - Chemical monitoring of river water bodies in an EU outermost region: examples
      from the Azores archipelago (Portugal).
AB  - Chemical monitoring of water quality on a total of 16 rivers in the Azores
      archipelago (Portugal), since 2003, made it possible to identify the major
      pressures and spatial geochemical variations along main course of the rivers.
      River water pollution is to a large extent associated to point sources, namely
      domestic wastewater discharges, especially in urban areas, and diffuse sources,
      associated with pasture land, and explain the high values on BOD(5) and nutrients
      (P and N). Heavy metals and metalloids, as well as hydrocarbons and pesticides,
      are generally under the detection limits of the analytical methods. Generally,
      river water reflects pollution loads according to a simple model, derived from
      land use in the watershed: in the upper part conditions are pristine, in the
      intermediate portion of the basin pasture land dominates and near the coast urban
      discharges are increasingly important. Results stress the role that an approach
      based on the watershed scale, coupled with land use management measures, are
      crucial to water management procedures and a successful WFD implementation in
      small river basin districts like the Azores. The paper also shows the need for
      full compliance regarding EU directives on urban wastewater and nitrate pollution
      due to agriculture.

PMID- 21076770
TI  - Identification of tetramethylarsonium in rice grains with elevated arsenic
      content.
AB  - Tetramethylarsonium has for the first time been identified in a commercially
      grown food product, rice, constituting up to 5.8% of the total arsenic in the
      rice.

PMID- 21076772
TI  - Intramolecular hydroalkoxylation in Bronsted acidic ionic liquids and its
      application to the synthesis of (+/-)-centrolobine.
AB  - The SO(3)H-tethered imidazolium and triazolium salts, nonvolatile and recyclable
      Bronsted acidic ionic liquids, efficiently mediate intramolecular
      hydroalkoxylations of alkenyl alcohols. They have been successfully employed in
      the synthesis of (+/-)-centrolobine.

PMID- 21076771
TI  - Synthesis of dysideaproline E using organocatalysis.
AB  - (S)-4,4-Dichloro-3-methylbutanoic acid was prepared in 51% overall yield from
      commercially available starting materials using an organocatalytic transfer
      hydrogenation to 4,4-dichloro-3-methylbut-2-enal in the key step. The (S)
      dichloro acid was used as an intermediate in the first total synthesis of
      dysideaproline E and a diastereomer confirming the structure of the natural
      product.

PMID- 21076773
TI  - Chemoselective phosphine-catalyzed cascade annulations between two different
      activated alkenes: highly diastereoselective syntheses of polysubstituted
      cyclohexanes and cyclopentenes.
AB  - Chemoselective phosphine-catalyzed cascade [2 + 2 + 2] and [2 + 2 + 1]
      annulations between two molecules of 2-arylmethylidene cyanoacetates or
      malononitriles and one molecule of alpha,beta-unsaturated ketones have been
      developed. Under the nucleophilic catalysis of PPh(3) or PBu(3) (10 mol%), a
      highly diastereoselective synthesis of polysubstituted cyclohexanes or
      cyclopentenes has been successfully achieved, respectively.

PMID- 21076774
TI  - Pyrimidine-pyrimidine base pairs stabilized by silver(I) ions.
AB  - In the presence of Ag(I) ions, the C-T and m(5)iC (5-methylisocytosine)-T base
      pairs showed comparable stability to the C-Ag(I)-C base pair, and the m(5)iC-C
      base pair was highly stabilized by the synergetic effect of Ag(I) coordination
      and possible hydrogen bonding.

PMID- 21076775
TI  - Predicting the coordination geometry for Mg2+ in the p53 DNA-binding domain:
      insights from computational studies.
AB  - Zn(2+) in the tumor-suppressor protein p53 DNA-binding domain (DBD) is essential
      for its structural stability and DNA-binding specificity. Mg(2+) has also been
      recently reported to bind to the p53DBD and influence its DNA-binding activity.
      In this contribution, the binding geometry of Mg(2+) in the p53DBD and the
      mechanism of how Mg(2+) affects its DNA-binding activity were investigated using
      density functional theory (DFT) calculations and molecular dynamics (MD)
      simulations. Various possible coordination geometries of Mg(2+) binding to
      histidines (His), cysteines (Cys), and water molecules were studied at the
      B3LYP/6-311+g** level of theory. The protonation state of Cys and the environment
      were taken into account to explore the factors governing the coordination
      geometry. The free energy of the reaction to form the Mg(2+) complexes was
      estimated, suggesting that the favorable binding mode changes from a four- to six
      coordinated geometry as the number of the protonated Cys increases. Furthermore,
      MD simulations were employed to explore the binding modes of Mg(2+) in the active
      site of the p53DBD. The simulation results of the Mg(2+) system and the native
      Zn(2+) system show that the binding affinity of Mg(2+)to the p53DBD is weaker
      than that of Zn(2+), in agreement with the DFT calculation results and
      experiments. In addition, the two metal ions are found to make a significant
      contribution to maintain a favorable orientation for Arg248 to interact with
      putative DNA, which is critically important to the sequence-specific DNA-binding
      activity of the p53DBD. However, the effect of Mg(2+) is less marked.
      Additionally, analysis of the natural bond orbital (NBO) charge transfer reveals
      that Mg(2+) has a higher net positive charge than Zn(2+), leading to a stronger
      electrostatic attractive interaction between Mg(2+) and putative DNA. This may
      partly explain the higher sequence-independent DNA-binding affinity of p53DBD
      Mg(2+) compared to p53DBD-Zn(2+) observed in experiment.

PMID- 21076776
TI  - Water-soluble, self-assembling container molecules: an update.
AB  - Over the past five years, an important development in the area of self-assembling
      containers has been the increase in interest in those containers that function in
      aqueous solution. This progress is a reflection of a similar trend within
      supramolecular chemistry in general, and is driven in part by the need to address
      issues and challenges within the biological sciences, as well as a desire to
      develop new strategies for greener chemistries carried out in water. It is also
      an opportunity to learn more about fundamental topics such as the hydrophobic
      effect. In this critical review we discuss progress in aqueous-based self
      assembling container molecules since 2005 (177 references).

PMID- 21076778
TI  - Microenvironment array chip for cell culture environment screening.
AB  - We have developed a microarray of cell culture environments composed of a
      combination of soluble factors and extracellular matrices for screening of cell
      culture environment.

PMID- 21076779
TI  - Guanidiniocarbonyl-pyrrole-aryl conjugates as nucleic acid sensors: switch of
      binding mode and spectroscopic responses by introducing additional binding sites
      into the linker.
AB  - Two novel guanidiniocarbonyl pyrrole-pyrene conjugates 3 and 4 as spectroscopic
      probes for ds-polynucleotides were synthesized and their interaction with
      different ds-DNAs/RNAs studied. Compared to a previously reported first set of
      conjugates (1 and 2) the significant extension and increased rigidity of the
      central part of the structure resulted in a switch of DNA binding mode from
      intercalative (previously studied derivatives 1 and 2 with a nonbinding and
      flexible linker) to minor groove binding of the two novel guanidiniocarbonyl
      pyrrole-pyrene conjugates 3 and 4. These two compounds interact strongly with ds
      DNAs, but only weakly with ds-RNA. The newly incorporated heterocyclic moieties
      within the central part of the structure of 3 and 4 were able to control by
      steric and hydrogen-bonding effects the alignment of the molecules within
      various, structurally different forms of DNA minor grooves, whereby even small
      differences in the position of the attached pyrene within the groove were
      reflected in different fluorimetric responses. In addition, 3 and 4 revealed
      intriguing in vitro selectivity among various human tumour cell lines.

PMID- 21076781
TI  - Chemical investigation of light induced DNA bipyrimidine damage and repair.
AB  - In all organisms, genetic information is stored in DNA and RNA. Both of these
      macromolecules are damaged by many exogenous and endogenous events, with UV
      irradiation being one of the major sources of damage. The major photolesions
      formed are the cyclobutane pyrimidine dimers (CPD), pyrimidine-pyrimidone-(6-4)
      photoproducts, Dewar valence isomers and, for dehydrated spore DNA, 5-(alpha
      thyminyl)-5,6-dihydrothymine (SP). In order to be able to investigate how
      nature's repair and tolerance mechanisms protect the integrity of genetic
      information, oligonucleotides containing sequence and site-specific UV lesions
      are essential. This tutorial review provides an overview of synthetic procedures
      by which these oligonucleotides can be generated, either through phosphoramidite
      chemistry or direct irradiation of DNA. Moreover, a brief summary on their usage
      in analysing repair and tolerance processes as well as their biological effects
      is provided.

PMID- 21076783
TI  - Main-chain supramolecular block copolymers.
AB  - Block copolymers are key building blocks for a variety of applications ranging
      from electronic devices to drug delivery. The material properties of block
      copolymers can be tuned and potentially improved by introducing noncovalent
      interactions in place of covalent linkages between polymeric blocks resulting in
      the formation of supramolecular block copolymers. Such materials combine the
      microphase separation behavior inherent to block copolymers with the
      responsiveness of supramolecular materials thereby affording dynamic and
      reversible materials. This tutorial review covers recent advances in main-chain
      supramolecular block copolymers and describes the design principles, synthetic
      approaches, advantages, and potential applications.

PMID- 21076780
TI  - Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4
      dicarboxylates.
AB  - Based on structural analysis of the human 2-oxoglutarate (2OG) dependent JMJD2
      histone N(epsilon)-methyl lysyl demethylase family, 3-substituted pyridine 2,4
      dicarboxylic acids were identified as potential inhibitors with possible
      selectivity over other human 2OG oxygenases. Microwave-assisted palladium
      catalysed cross coupling methodology was developed to install a diverse set of
      substituents on the sterically demanding C-3 position of a pyridine 2,4
      dicarboxylate scaffold. The subsequently prepared di-acids were tested for in
      vitro inhibition of the histone demethylase JMJD2E and another human 2OG
      oxygenase, prolyl-hydroxylase domain isoform 2 (PHD2, EGLN1). A subset of
      substitution patterns yielded inhibitors with selectivity for JMJD2E over PHD2,
      demonstrating that structure-based inhibitor design can enable selective
      inhibition of histone demethylases over related human 2OG oxygenases.

PMID- 21076782
TI  - Characterization and application of a DNA aptamer binding to L-tryptophan.
AB  - DNA aptamers for specific recognition of L-tryptophan have been evolved by a
      SELEX (systematic evolution of ligands by exponential enrichment) technique.
      Truncation-mutation experiments suggest that a 34-mer sequence, Trp3a-1,
      possesses the strongest binding ability to L-tryptophan. Trp3a-1 is predicted to
      adopt a loop-stem secondary structure, in which the loop may further fold into a
      binding pocket for L-tryptophan with the help of the stem. The specificity
      investigation shows that Trp3a-1 strongly binds to L-tryptophan, has almost no
      binding to other amino acids, and weakly binds to some tryptophan analogs and
      peptides containing the L-tryptophan residue. The binding of Trp3a-1 to L
      tryptophan is mainly contributed to by hydrogen bonds and precise stacking formed
      between the binding pocket of Trp3a-1 and all groups on L-tryptophan. This
      aptamer has also been proved to be an effective ligand for the chiral separation
      of D/L-tryptophan. L-tryptophan and its derivatives are known to play important
      biological roles; this aptamer ligand could be used as a tool for the analysis of
      tryptophan and other related studies.

PMID- 21076784
TI  - Sandwich-type mixed (phthalocyaninato)(porphyrinato) rare earth double-decker
      complexes with decreased molecular symmetry of Cs: single crystal structure and
      self-assembled nano-structure.
AB  - Two novel sandwich-type mixed (phthalocyaninato)(porphyrinato) rare earth double
      decker complexes with decreased molecular symmetry of Cs
      M(Pc)[D(NHC(8)H(17))(2)PP] [M = Eu, Lu; Pc = unsubstituted phthalocyaninate;
      D(NHC(8)H(17))(2)PP = 5,10-di(phenyl)-15,20-di(4-octylamino-phenyl)porphyrinate]
      (1, 2) have been designed, prepared, and characterized. The single crystal and
      molecular structure of the Eu analogue has been determined by X-ray diffraction
      analysis, revealing the head-to-tail supramolecular chains formed from closely
      bound double-decker molecules depending on the N-H-N hydrogen bonds between one
      octyl-substituted amidocyanogen group attached at the p-position of meso-attached
      phenyl group of the porphyrin ligand in the mixed ring double-decker molecule and
      one aza-nitrogen atom of the phthalocyanine ring in the neighboring double-decker
      molecule in a zigzag form. Their self-assembled nano-structures have been
      investigated by transmission electronic microscopy (TEM) and scanning electronic
      microscopy (SEM). Intermolecular H-N-H hydrogen bonding interaction leads to the
      formation of nano-structures with fusiform morphology with 220-250 nm average
      width and about 10 MUm length for 1 and 300 nm width and 3-5 MUm length for 2,
      respectively, revealing the effect of molecular size in the direction
      perpendicular to the tetrapyrrole ring on the dimensions of self-assembled nano
      structures.

PMID- 21076785
TI  - A cryogen-free refrigerating preconcentration device for the measurement of C2 to
      C4 hydrocarbons in ambient air.
AB  - A cryogen-free refrigerating preconcentration device for the enrichment of trace
      amounts of highly volatile organic compounds in the atmosphere prior to analysis
      has been designed and evaluated. The device consists of a microtrap housed in an
      insulated box, which is cooled by a conventional refrigeration unit. Experimental
      parameters, including adsorbent mass, trapping temperature, and thermal
      desorption temperature, were optimized. The on-line coupling of the device to a
      GC allows sufficient enrichment and separation of C2 to C4 hydrocarbons in less
      than 40 min without a second cryotrap. The target compounds analysis showed good
      linearity (correlation coefficients >0.99) and repeatability (relative standard
      deviation <5%). Detection limits for the 10 volatile organic compounds ranged
      from 14 ppt to 52 ppt, under the conditions of a 500 mL sampling volume and -10 
      degrees C trapping temperature. Real air sample measurements were conducted at an
      urban site, and five VOCs including ethane, ethene, propane, propene and 1-butene
      were detected and quantified.

PMID- 21076786
TI  - Vibrationally promoted electron emission at a metal surface: electron kinetic
      energy distributions.
AB  - We report the first direct measurement of the kinetic energy of exoelectrons
      produced by collisions of vibrationally excited molecules with a low work
      function metal surface exhibiting electron excitations of 64% (most probable) and
      95% (maximum) of the initial vibrational energy. This remarkable efficiency for
      vibrational-to-electronic energy transfer is in good agreement with previous
      results suggesting the coupling of multiple vibrational quanta to a single
      electron.

PMID- 21076787
TI  - [Mental health in Haiti: a joint action].

PMID- 21076788
TI  - [Culture and mental health in Haiti : a literature review].
AB  - This paper reviews and summarizes the available literature on Haitian mental
      health and mental health services. This review was conducted in light of the
      Haitian earthquake in January 2010. We searched Medline, Google Scholar and other
      available databases to gather scholarly literature relevant to mental health in
      Haiti. This was supplemented by consultation of key books and grey literature
      relevant to Haiti. The first part of the review describes historical, economic,
      sociological and anthropological factors essential to a basic understanding of
      Haiti and its people. This includes discussion of demography, family structure,
      Haitian economics and religion. The second part of the review focuses on mental
      health and mental health services. This includes a review of factors such as
      basic epidemiology of mental illness, common beliefs about mental illness,
      explanatory models, idioms of distress, help-seeking behavior, configuration of
      mental health services and the relationship between religion and mental health.

PMID- 21076789
TI  - [Full conscious meditation and psychotherapy in health and illness: literature
      review].
AB  - This research aims at delimitating the realm of meditation as therapeutic care in
      the field of the health psychology. The authors concentrate on the most prolific
      current of these last years in research terms : the meditation in full
      consciousness. The objective is to define the concept of meditation and full
      consciousness, to then pay attention on the relevant psychotherapies and clinical
      studies in this domain. Meditation in full consciousness constitutes a very
      promising field of research for health psychology within the framework of care.
      Techniques such as MBSR, MBCT applied to the full consciousness turns out
      relevant and result in improvement of general health. However, studies on full
      consciousness are still at very early stage and more rigorous approaches on a
      methodological level and refined conceptual developments are necessary.

PMID- 21076790
TI  - [Childhood experiences of the Duplessis children: consequences 50 years later].
AB  - In this article, the authors present qualitative results, derived from
      questionnaires and semi-structured interviews, to describe past and present
      experiences of the Duplessis children. Examples representative of their
      experience and a detailed description of two cases are provided. Results indicate
      that childhood abuse and negligence are related to poorer long-term psychological
      adjustment. The findings also demonstrate that reporting at least four strengths
      in childhood can have long-term protective effects.

PMID- 21076791
TI  - [Does dissociative schizophrenia exist?].
AB  - On a phenomenological level, there's an important overlap between dissociative
      and psychotic symptoms. Furthermore, traumatic etiology, recognized in
      dissociative disorders, is also increasingly considered in psychosis. These
      similarities create confusion in clinical settings with important repercussions
      for individuals suffering from these disorders. Indeed, difficulties encountered
      in differential diagnoses could result in an erroneous diagnosis or in an
      undetected comorbidity. Some authors are going further in suggesting that there
      is a sub-type of schizophrenia having dissociation behind the expression of
      psychotic symptoms.

PMID- 21076792
TI  - [Studies of cost/effectiveness of pharmacological and psychological treatment of
      anxiety disorders: a literature review].
AB  - This article reviews the literature on economic studies of evidence-based
      cognitive-behavioral treatment and pharmacotherapy for anxiety disorders.
      Articles were identified through electronic search of medical and psychological
      databases between 1980 and 2008. Seven studies were identified and included panic
      disorder, generalized anxiety disorder, specific phobia and social phobia.
      Results show that evidence-based cognitive-behavior therapy and pharmacotherapy
      are cost-effective, usually more than usual care. Although the evidence base
      needs to be strengthened, it appears beneficial in increasing access to evidence
      based treatments for anxiety disorders from a societal perspective.

PMID- 21076793
TI  - [Knowledge and beliefs of professional workers in education, health and social
      services towards ADHD].
AB  - This study aims at better understanding the knowledge and beliefs of professional
      workers in school, health and social service settings in Quebec regarding ADHD.
      The authors examine the important discrepancies identified by Cohen (1999)
      between identified standard practices in treating ADHD patients and practices
      used in Quebec. This situation could be linked to insufficient knowledge of
      workers or certain of their beliefs that oppose these practices and their
      reluctance to implement them in their environment. Two measurement scales were
      utilised : the Attention Deficit Hyperactivity Disorder Orientation Scale
      (ADHDOS, Couture, 2002) and the Survey of ADHD of Jerome and al. (1994). Results
      show among other things, that knowledge and beliefs vary according to
      professionals'background and training.

PMID- 21076794
TI  - [A critical review of the organizational engineering of Quebec's mental health
      action plan].
AB  - The Plan d'action en sante mentale 2005-2010 commands a substantial reform of
      mental health services organization. In order to achieve this, the Plan draws
      upon a set of ideas that appear somewhat unsubstantiated in regards to the
      sciences of organization. This article examines a few of these ideas. The
      managerial rhetoric of the Plan is anchored in an organizational and mechanistic
      archetype known for its inadequacy in the central mission of organizations of
      complex human services such as those concerning mental health. The mechanist
      rationality adopted marginalizes the real source of the value of mental health
      services, of practitioners and their social institutions. It participates in a
      movement that renders organizations always bigger, more abstract and impersonal
      steered from a distance by superficial indicators. There are good reasons to
      believe that this approach of organizational engineering will accentuate the
      eroding of the individual and collective capacities of delivering services of
      great value.

PMID- 21076795
TI  - [Giving birth at 16, without violence: a possible reality? Empirical data and
      critical reflection].
AB  - Violence between adolescents during teen pregnancy is relatively new in terms of
      scientific interest and clinical preoccupations. It is an alarming situation,
      given that 1) its prevalence ranges from 5 % to 29 % according to the literature;
      2) consequences for both the mother's and baby's health are numerous at physical,
      psychological and sexual levels; 3) scientific and empirical knowledge regarding
      the phenomenon is limited and diminishes efficacy and relevance of current
      interventions. It therefore appears of major importance to acquire better
      knowledge of various ecological factors in order to implement preventative care
      and services that will allow them as well as their children to thrive in adverse
      conditions and have access to a safe and supportive environment.

PMID- 21076796
TI  - [Generalized anxiety disorder: recognizing it and understanding its impact on the
      cognitive functioning].
AB  - Since the appearance of Generalized Anxiety Disorder (GAD) in the 1980 version of
      the Diagnostic and Statistical Manual of Mental Disorders (DSM), the definition
      and the comprehension of this disorder have largely evolved. The present article
      is an overview of the principal aspects of GAD in the literature such as the
      history, the prevalence, the socioeconomic characteristics, the comorbidity, the
      differential diagnosis and its evolution, while considering the litigious
      questions concerning its classification. This article also presents a report of
      the recent studies about the cognitive profile of patients, from a perspective of
      cognitive experimental psychology and neuropsychology. The consequences on
      cognitive functioning are discussed in the second part of the article, as well as
      precautions relatively to functioning clinicians have to consider.

PMID- 21076797
TI  - Physical fitness and associations with anthropometric measurements in 7 to 15
      year-old school children.
AB  - OBJECTIVE: To analyze associations between health-related physical fitness and
      the anthropometric and demographic indicators of children at three elementary
      schools in Botucatu, SP, Brazil. METHODS: The sample for this cross-sectional
      study was 988 elementary school students, recruited from the second to ninth
      grades (an age range of 7 to 15 years). The children underwent anthropometric
      assessment (weight, height, waist circumference and tricipital and subscapular
      skin folds) and were tested for health-related physical fitness (flexibility: sit
      and reach test; abdominal strength/stamina: 1-minute abdominal test; and aerobic
      stamina: 9-minute running/walking test). Data were analyzed using descriptive
      statistics plus Student's t test, the chi-square test or Fisher's exact test and
      logistic regression with a significance level of 5%. RESULTS: The physical
      fitness levels observed were significantly influenced by age (all levels), sex
      (abdominal strength/stamina), obesity (all levels), body adiposity (flexibility,
      abdominal strength/stamina) and abdominal adiposity (abdominal strength/stamina
      and aerobic stamina). Females were more prone to be unfit in abdominal
      strength/stamina. Both obesity and excessive abdominal adiposity predisposed
      children to be unfit in abdominal strength/stamina and aerobic stamina. Excess
      body adiposity increased the likelihood of poor trunk flexibility. CONCLUSIONS:
      Unhealthy physical fitness levels were related to female sex, obesity and
      excessive abdominal adiposity. Implementing programs designed to effect lifestyle
      changes to achieve physical fitness and healthy nutrition in these schools would
      meet the objectives of promoting healthy body weight and increased physical
      fitness among these schoolchildren.

PMID- 21076798
TI  - Persistent operational challenges lead to non-reduction in maternal-infant
      transmission of HIV.
AB  - OBJECTIVE: To determine impediments to the effective reduction of maternal-infant
      transmission of HIV in the municipality of Campos dos Goytacazes, RJ, Brazil.
      METHODS: This is a cohort study, with medical follow-up, of pregnant women with
      confirmed diagnosis of HIV infection, and their infant children, assisted at the
      Municipal Specialized Service of Sexually Transmitted Diseases/AIDS from January
      2004 to April 2007. Information regarding exposure and outcome variables was
      collected from their medical records. Frequencies of variables were determined
      and bivariate analysis performed for exposure factors and transmission of HIV.
      Relative risks of HIV transmission associated with exposure variables were
      calculated using 95% confidence intervals. Statistical significance of risk
      associations was evaluated. RESULTS: Seventy-eight mother-child pairs were
      studied; the rate of maternal-infant transmission of HIV was 7.7%. Variables
      showing significant association with maternal-infant transmission of HIV were the
      non-utilization of antiretrovirals for prophylaxis or treatment during pregnancy
      (RR = 21.00; 95%CI 2.64-166.74, p = 0.001) and diagnosis of maternal disease
      after pregnancy (RR = 6.80; 95%CI 1.59-29.17, p = 0.025). New pregnancies in
      women with other children also exposed to HIV occurred in 19.12% (15/78) of
      cases. CONCLUSIONS: There was no reduction in the rate of maternal-infant
      transmission of HIV in the period 2004-2007 in relation to the preceding
      triennium. The following were recognized as impediments to the effective
      reduction of maternal-infant transmission of HIV: low prenatal screening coverage
      of maternal HIV infection, impairing maternal treatment or prophylaxis; and the
      incorrect use of the rapid screening test at admission for delivery.

PMID- 21076799
TI  - Polycystic ovary syndrome and acne.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in
      reproductive aged women. It is typically characterized by hyperandrogenism,
      chronic anovulation, and polycystic ovaries. Women with PCOS often experience
      dermatologic manifestations of hyperandrogenism, including hirsutism, acne
      vulgaris, and androgenic alopecia. This article will review the treatments for
      acne due to androgen excess in PCOS women.

PMID- 21076800
TI  - Benzoyl peroxide: enhancing antibiotic efficacy in acne management.
AB  - Benzoyl peroxide is one of the most widely used topical agents for acne. It has
      potent antibacterial and mild anti-inflammatory and comedolytic effects. To treat
      mild to moderate acne, it can be used alone or in combination with topical
      antibiotics and topical retinoids. The combination of benzoyl peroxide with
      either erythromycin or clindamycin is synergistic and well-tolerated. In more
      severe acne, when oral antibiotics are required, benzoyl peroxide can contribute
      to suppressing the emergence of resistant strains of Propionibacterium acnes.

PMID- 21076801
TI  - Vertebral pneumatization.

PMID- 21076802
TI  - [Physiology of anastomotic healing].
AB  - Anastomotic insufficiency still remains the most dreaded complication following
      digestive surgery. The surgeon's understanding of the mechanisms underlying
      anastomotic healing and the possible weak points are just as important as a
      correct anastomotic technique. Intestinal anastomotic healing is a complex, cell
      mediated process which aims at restoring bowel wall continuity. The early stages
      of anastomotic healing are most susceptible to various sources of irritation,
      which is reflected by the likelihood of early anastomotic insufficiency. In our
      opinion, the focus of future research should shift from primarily examining
      pathogenetic factors to a more cellular and molecular level. A better
      comprehension of the anastomotic healing process might thus promote the
      development of new diagnostic predictive and therapeutic methods.

PMID- 21076803
TI  - [The specific dermatoses of pregnancy].
AB  - The specific dermatoses of pregnancy represent a heterogeneous group of
      inflammatory skin diseases related to pregnancy and/or the postpartum period. The
      most recent classification includes pemphigoid gestationis, polymorphic eruption
      of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of
      pregnancy. The hallmark of all four entities is severe pruritus that is
      accompanied by characteristic skin changes. While some of these dermatoses are
      distressing only to the mother because of pruritus, others may be associated with
      significant fetal risks. Early diagnosis and prompt treatment are therefore
      essential. In this review, we will discuss the various pregnancy dermatoses in
      detail and present an algorithm for diagnosis and management of pruritus in
      pregnancy.

PMID- 21076804
TI  - [Chronic inflammatory and autoimmune mediated dermatoses during pregnancy. Course
      and prognosis for mother and child].
AB  - Chronic inflammatory dermatoses during pregnancy can take varying courses in
      mother and child. The dominant Th2-response characteristic for pregnancy may
      explain why atopic eczema or lupus erythematosus may deteriorate while psoriasis
      vulgaris may improve. In contrast, impetigo herpetiformis frequently shows a
      severe course. Lupus erythematosus and other autoantibody-triggered dermatoses
      like pemphigus vulgaris pose an increased risk for the child because of placental
      transfer of autoantibodies with specific skin changes or systemic manifestations
      of the disease as well as placental insufficiency, growth retardation and
      premature birth. Such risks are not associated with linear IgA dermatosis. A
      severe pityriasis rosea during the first 20 weeks of pregnancy may lead to an
      increased risk of abortion or premature delivery. Early diagnosis and
      individually adjusted therapy of skin diseases is mandatory to avoid any risk for
      mother or child.

PMID- 21076806
TI  - [Physician-assisted suicide in dementia?].
AB  - Physician-assisted suicide in Germany is limited by criminal law and disapproved
      by professional authorities. A physician who is willing to help a demented
      patient in terminating his life has to be definitely sure that the disease does
      not interfere with the patient's capacity for decision-making. In cases of early
      dementia the reason why assisted suicide will usually be requested is not the
      actual suffering of the patient but his negative expectations for the future. As
      long as there are sufficient opportunities for palliative care, the progressive
      course of the dementia process does not imply a state of unbearable suffering
      which could justify an assisted suicide. Nevertheless there may be certain
      circumstances--as for instance the value that an individual attributes to his
      integrity or to the narrative unity of his life--which might possibly provide an
      ethical justification for the assistance in life termination. A physician who
      helps a demented person in performing a suicidal act does not necessarily oppose
      essential principles of medical ethics. Yet, especially with regard to possible
      societal consequences of physician-assisted suicide in dementia, the rejecting
      attitude of medical authorities against that activity must be considered as well
      founded and legitimate. Deviations from these general guidelines ought to be
      respected as long as they are limited to exceptional situations and correspond to
      a thorough consideration of a physician's professional duties. They should remain
      open to public control, but not be ultimately specified by unequivocal normative
      regulations.

PMID- 21076805
TI  - [Melanoma and pregnancy].
AB  - The incidence of melanoma has steadily increased in recent years. As women of
      childbearing age are also increasing being affected, questions about birth
      control, hormonal contraception and necessary procedures in case of pregnancy are
      spotlighted when counseling this group of patients. A potentially adverse effect
      of pregnancy on melanoma risk and prognosis has been discussed for decades.
      Giving advice to pregnant melanoma patients concerning diagnostic and therapeutic
      decisions often requires interdisciplinary collaboration of the treating
      clinicians, especially in cases of progressive metastatic disease.

PMID- 21076807
TI  - [New possibilities for automated diagnosis of dementia].
AB  - Dementia is underdiagnosed and undertreated in Germany. Automatic diagnosing of
      dementia based on standard magnetic resonance imaging has the capacity to reduce
      diagnostic uncertainties. The algorithm learns a disease specific pattern of
      atrophy from training samples. It is independent from radiological expertise
      which may be scarce outside specialised centres and can be installed on MRT
      machines or desktop PCs. It can also play its part in planning and conducting
      treatment trials by recruiting a sample with predicted fast future decline.
      Extension, based e.g. on resting state functional imaging are possible but are
      further away from clinical routine.

PMID- 21076808
TI  - [Functional neuroimaging of neglect].
AB  - Though the neglect syndrome is often observed in clinical practice, there are few
      studies investigating its mechanisms or developing new therapeutic approaches.
      Most studies on attention were conducted in healthy subjects. In this paper I
      provide functional neuroimaging data about functional networks for stimuli
      perception independently from their modality. Additionally, the restoration of
      stimulus perception and its modulation through emotion are discussed.

PMID- 21076809
TI  - [3 T MRI of the prostate in patients with symptomatic prostatic utricle cyst].
AB  - Cystic lesions of the prostate are rare and often asymptomatic. Medial cysts are
      conventionally divided into so-called Mullerian duct cysts and prostatic utricle
      cysts which seems rather questionable in light of recent studies. We report a
      case of a patient with a 10-year history of dysuria. Diagnostic imaging was
      performed using 3 T prostate MRI with a body coil. Because of the potential risk
      of retrograde ejaculation with subsequent infertility and of incontinence by the
      transurethral resection, the interventional therapy of his utricle cyst was
      abandoned.

PMID- 21076810
TI  - Characterization of opaque2 modifier QTLs and candidate genes in recombinant
      inbred lines derived from the K0326Y quality protein maize inbred.
AB  - Quality protein maize (QPM) is a high lysine-containing corn that is based on
      genetic modification of the opaque2 (o2) mutant. In QPM, modifier genes convert
      the starchy endosperm of o2 to the vitreous phenotype of wild type maize. There
      are multiple, unlinked o2 modifier loci (Opm) in QPM and their nature and mode of
      action are unknown. We previously identified seven Opm QTLs and characterized 16
      genes that are differentially up-regulated at a significant level in K0326Y QPM,
      compared to the starchy endosperm mutant W64Ao2. In order to further characterize
      these Opm QTLs and the genes up-regulated in K0326Y QPM, we created a population
      of 314 recombinant inbred lines (RILs) from a cross between K0326Y QPM and
      W64Ao2. The RILs were characterized for three traits associated with endosperm
      texture: vitreousness, density and hardness. Genetic linkage analysis of the RIL
      population confirmed three of the previously identified QTLs associated with o2
      endosperm modification in K0326Y QPM. Many of the genes up-regulated in K0326Y
      QPM showed substantially higher levels of expression in vitreous compared with
      opaque RILs. These included genes associated with the upstream regulation of the
      ethylene response pathway, and a gene encoding a regulatory subunit of
      pyrophosphate-dependent fructose-6-phosphate 1-phosphotransferase, an adaptive
      enzyme of the glycolytic pathway.

PMID- 21076811
TI  - The genetic characterisation of stripe rust resistance in the German wheat
      cultivar Alcedo.
AB  - Stripe rust resistance in the German winter wheat cv. Alcedo has been described
      as durable, the resistance having remained effective when grown extensively in
      Germany and Eastern Europe between 1975 and 1989. Genetic characterisation of
      field resistance in a cross between Alcedo and the stripe rust susceptible UK
      winter wheat cv. Brigadier identified two major QTL in Alcedo located on the long
      arms of chromosomes 2D (QPst.jic-2D) and 4B (QPst.jic-4B). Stripe rust resistance
      was evaluated by measuring the extent of fungal growth, percentage infection (Pi)
      and the necrotic/chlorotic response of the plant to infection, infection type
      (IT). Both QPst.jic-2D and QPst.jic-4B contributed significantly to the reduction
      in stripe rust infection (Pi), with QPst.jic-2D explaining up to 36.20% and
      QPst.jic-4B 28.90% of the phenotypic variation measured for Pi. Both QTL were
      identified by the IT phenotypic scores, with QPst.jic-2D in particular being
      associated with a strong necrotic phenotype (low IT), QPst.jic-2D explaining up
      to 53.10% of IT phenotypic variation and QPst.jic-4B 22.30%. In addition, two
      small effect QTL for field stripe rust resistance were identified in Brigadier,
      QPst.jic-1B on the long arm of chromosome 1B and QPst.jic-5A on the short arm of
      chromosome 5A. The influence of QPst.jic-1B was primarily seen with the Pi
      phenotype, contributing up to 13.10% of the explained phenotypic variation.
      QPst.jic-5A was only detected using an approximate multiple-QTL model and
      selecting markers linked to the major effect QTL, QPst.jic-2D and QPst.jic-4B as
      co-factors. Seedling stripe rust resistance was also mapped in the cross, which
      confirmed the location of Yr17 from Brigadier to the short arm of chromosome 2A.
      A seedling expressed QTL was also located in Alcedo that mapped to the same
      location as the field stripe rust resistance QPst.jic-2D.

PMID- 21076812
TI  - Patterns of polymorphism and linkage disequilibrium in cultivated barley.
AB  - We carried out a genome-wide analysis of polymorphism (4,596 SNP loci across 190
      elite cultivated accessions) chosen to represent the available genetic variation
      in current elite North West European and North American barley germplasm.
      Population sub-structure, patterns of diversity and linkage disequilibrium varied
      considerably across the seven barley chromosomes. Gene-rich and rarely
      recombining haplotype blocks that may represent up to 60% of the physical length
      of barley chromosomes extended across the 'genetic centromeres'. By positioning
      2,132 bi-parentally mapped SNP markers with minimum allele frequencies higher
      than 0.10 by association mapping, 87.3% were located to within 5 cM of their
      original genetic map position. We show that at this current marker density
      genetically diverse populations of relatively small size are sufficient to fine
      map simple traits, providing they are not strongly stratified within the sample,
      fall outside the genetic centromeres and population sub-structure is effectively
      controlled in the analysis. Our results have important implications for
      association mapping, positional cloning, physical mapping and practical plant
      breeding in barley and other major world cereals including wheat and rye that
      exhibit comparable genome and genetic features.

PMID- 21076813
TI  - Arthroscopic debridement of the isolated Ligamentum Teres rupture.
AB  - PURPOSE: Most tears of the Ligamentum Teres (LT) are diagnosed when treating
      other hip pathologies. The purpose of this study was to evaluate the outcome of
      arthroscopic surgery for a unique group of patients with symptomatic isolated
      Ligamentum Teres rupture of the hip. METHODS: The study included 29 patients who
      suffered from an isolated Ligamentum Teres rupture of the hip and were treated
      with an arthroscopic debridement from 2003 to 2008. Patients with
      femoroacetabular impingement or other hip pathologies except Ligamentum Teres
      tear were excluded. Clinical results were measured preoperatively and
      postoperatively with the modified Harris Hip Score (MHHS) and Non-Arthritic Hip
      Score (NAHS). The mean age was 25 years (SD +/- 11) with a mean follow-up time of
      2.5 years (SD +/- 1.5). RESULTS: At the last follow-up, the mean MHHS improved
      from 70 to 86 [mean difference = 16 (95% CI 4-27)] and the mean NAHS improved
      from 64 to 86 [mean difference = 22 (95% CI 10-33)]. Five patients have had a
      second arthroscopic debridement due to symptomatic recurrent tears. CONCLUSION:
      Arthroscopic debridement alone of the isolated Ligamentum Teres rupture has a
      short-term beneficial result in more than 80% of cases.

PMID- 21076814
TI  - Postoperative blood loss management in total knee arthroplasty: a comparison of
      four different methods.
AB  - PURPOSE: As the blood loss after the total knee arthroplasty (TKA) is not only a
      potentially serious medical problem but also an economical concern, the purpose
      of the study was to investigate the effectiveness of different combinations of
      knee positioning and the applied wound dressings on blood saving after TKA.
      METHODS: A randomized controlled trial including 147 TKA-operated patients was
      conducted. The subjects were assigned to one of the four groups; Group 1
      controls, Group 2-flexion, Group 3-flexion and compression, Group 4-compression.
      The main outcome measures of the study were the blood loss volumes during the
      procedure and in the intensive care rooms and the decreases in haemoglobin,
      haemotocrit and red blood cells on the first and the second postoperative day.
      RESULTS: The MANOVA results showed no differences between the groups in any of
      the observed parameters. The post-hoc comparisons of the each group to the
      control group also revealed no influence of any of the proposed blood saving
      techniques on the actual blood loss. CONCLUSION: No significant differences among
      the four proposed blood saving methods were determined.

PMID- 21076815
TI  - The use of the Tegner Activity Scale for articular cartilage repair of the knee:
      a systematic review.
AB  - PURPOSE: The Tegner Activity Scale (TAS) was developed in 1984 and has been
      widely used in studies on knee populations. The primary objective of this study
      was to undertake a systematic review on the use of the TAS for articular
      cartilage repair (ACR) of the knee. METHODS: A systematic review was conducted
      using electronic databases (MEDLINE, CINAHL, SPORTDiscusTM, NHS Evidence, ISI Web
      of Knowledge, AMED, BNI, PEDro and The Cochrane Collaboration of Systematic
      Reviews) and reference lists from extracted articles. Studies were selected that
      were published between 1984 and 2009 in which the TAS was reported for patients
      who had undergone ACR of the knee. RESULTS: The search strategy identified 442
      citations of which 34 articles met the inclusion criteria. There was a large
      degree of study heterogeneity especially regarding data reporting a wide
      variation in the number of participants (range 5-137), participant age (range 12
      76 years), follow-up time (range 3-120 months) and male-to-female participant
      ratio. Where pre- to postoperative TAS change was analysed, 88% of studies
      demonstrated a significant improvement in postoperative TAS scores. CONCLUSIONS:
      In general, TAS data were inconsistently reported and methodological detail was
      often lacking. Caution is advised in the interpretation of TAS scores following
      ACR of the knee where there are large ranges in postoperative follow-up times,
      mixed gender cohorts and wide ranges in participant ages. TAS data should be
      presented and analysed fully and ideally in a standardised fashion to facilitate
      the comparison of outcomes between studies.

PMID- 21076816
TI  - Coastal bacterioplankton community diversity along a latitudinal gradient in
      Latin America by means of V6 tag pyrosequencing.
AB  - The bacterioplankton diversity of coastal waters along a latitudinal gradient
      between Puerto Rico and Argentina was analyzed using a total of 134,197 high
      quality sequences from the V6 hypervariable region of the small-subunit ribosomal
      RNA gene (16S rRNA) (mean length of 60 nt). Most of the OTUs were identified into
      Proteobacteria, Bacteriodetes, Cyanobacteria, and Actinobacteria, corresponding
      to approx. 80% of the total number of sequences. The number of OTUs corresponding
      to species varied between 937 and 1946 in the seven locations. Proteobacteria
      appeared at high frequency in the seven locations. An enrichment of Cyanobacteria
      was observed in Puerto Rico, whereas an enrichment of Bacteroidetes was detected
      in the Argentinian shelf and Uruguayan coastal lagoons. The highest number of
      sequences of Actinobacteria and Acidobacteria were obtained in the Amazon estuary
      mouth. The rarefaction curves and Good coverage estimator for species diversity
      suggested a significant coverage, with values ranging between 92 and 97% for Good
      coverage. Conserved taxa corresponded to aprox. 52% of all sequences. This study
      suggests that human-contaminated environments may influence bacterioplankton
      diversity.

PMID- 21076817
TI  - What is 'anti' about anti-reaches? Reference frames selectively affect reaction
      times and endpoint variability.
AB  - Reach movement planning involves the representation of spatial target information
      in different reference frames. Neurons at parietal and premotor stages of the
      cortical sensorimotor system represent target information in eye- or hand
      centered reference frames, respectively. How the different neuronal
      representations affect behavioral parameters of motor planning and control, i.e.
      which stage of neural representation is relevant for which aspect of behavior, is
      not obvious from the physiology. Here, we test with a behavioral experiment if
      different kinematic movement parameters are affected to a different degree by
      either an eye- or hand-reference frame. We used a generalized anti-reach task to
      test the influence of stimulus-response compatibility (SRC) in eye- and hand
      reference frames on reach reaction times, movement times, and endpoint
      variability. While in a standard anti-reach task, the SRC is identical in the eye
      and hand-reference frames, we could separate SRC for the two reference frames.
      We found that reaction times were influenced by the SRC in eye- and hand
      reference frame. In contrast, movement times were only influenced by the SRC in
      hand-reference frame, and endpoint variability was only influenced by the SRC in
      eye-reference frame. Since movement time and endpoint variability are the result
      of planning and control processes, while reaction times are consequences of only
      the planning process, we suggest that SRC effects on reaction times are highly
      suited to investigate reference frames of movement planning, and that eye- and
      hand-reference frames have distinct effects on different phases of motor action
      and different kinematic movement parameters.

PMID- 21076818
TI  - Podokinetic stimulation causes shifts in perception of straight ahead.
AB  - Podokinetic after-rotation (PKAR) is a phenomenon in which subjects inadvertently
      rotate when instructed to step in place after a period of walking on a rotating
      treadmill. PKAR has been shown to transfer between different forms of locomotion,
      but has not been tested in a non-locomotor task. We conducted two experiments to
      assess effects of PKAR on perception of subjective straight ahead and on quiet
      standing posture. Twenty-one healthy young right-handed subjects pointed to what
      they perceived as their subjective straight ahead with a laser pointer while they
      were recorded by a motion capture system both before and after a training period
      on the rotating treadmill. Subjects performed the pointing task while standing,
      sitting on a chair without a back, and a chair with a back. After the training
      period, subjects demonstrated a significant shift in subjective straight ahead,
      pointing an average of 29.1 +/- 10.6 degrees  off of center. The effect was
      direction-specific, depending on whether subjects had trained in the clockwise or
      counter-clockwise direction. Postures that limited subjects' ability to rotate
      the body in space resulted in reduction, but not elimination, of the effect. The
      effect was present in quiet standing and even in sitting postures where
      locomotion was not possible. The robust transfer of PKAR to non-locomotor tasks,
      and across locomotor forms as demonstrated previously, is in contrast to split
      belt adaptations that show limited transfer. We propose that, unlike split-belt
      adaptations, podokinetic adaptations are mediated at supraspinal, spatial
      orientation areas that influences spinal-level circuits for locomotion.

PMID- 21076819
TI  - Physical delay but not subjective delay determines learning rate in prism
      adaptation.
AB  - Timing is critical in determining the causal relationship between two events.
      Motor adaptation relies on the timing of actions and their results for
      determining which preceding control signals were responsible for subsequent error
      in the resulting movements. An artificially induced temporal delay in error
      feedback as short as 50 ms has been found to slow the learning rate of prism
      adaptation. Recent studies have demonstrated that our sense of simultaneity is
      flexibly adaptive when a persistent delay is inserted into visual feedback timing
      of one's own action. Therefore, judgments of "subjective simultaneity" (i.e.
      whether two events are simultaneous on a subjective basis) do not necessarily
      correspond to the actual simultaneity of physical events. We evaluated the
      effects of adaptation to a temporal shift of subjective simultaneity on prism
      adaptation by examining whether prism adaptation depends on physical timing or
      subjective timing. We found that after persistently experiencing an additional
      100-ms delay in a pointing experiment, psychometric curves of the timing of
      judgments about the temporal order of touching and visual feedback were shifted
      by 40 ms, indicating that subjective simultaneity adapted. Next, while
      maintaining temporal adaptation, participants adapted to spatial displacement
      caused by a prism with and without an additional temporal delay in feedback.
      Learning speed was reliably predicted by physical timing but not by subjective
      timing. These results indicate that prism adaptation occurs independently of
      awareness of subjective timing and may be processed in primary motor areas that
      are thought to have fidelity with temporal relations.

PMID- 21076822
TI  - MR enterography of ileocolovesicular fistula in pediatric Crohn disease.
AB  - Crohn disease, a form of chronic inflammatory bowel disease is characterized by
      discontinuous inflammatory lesions of the gastrointestinal tract, has a variety
      of behavioral patterns, including penetrating or fistulous disease. While
      magnetic resonance enterography (MRE) excellently depicts inflamed bowel
      segments, it can also be used to assess for a variety of Crohn-disease-related
      extraintestinal complications, including fistulae. We present the MRE findings of
      a complex ileocolovesicular fistula in a 14-year-old boy with Crohn disease,
      where the fistulous tract to the urinary bladder was best delineated on
      precontrast T1-W imaging because of the presence of fecal material.

PMID- 21076820
TI  - Premovement brain activity in a bimanual load-lifting task.
AB  - Even the simplest volitional movements must be precisely coordinated with
      anticipatory postural adjustments. Little is currently known about the neural
      networks that coordinate these adjustments in healthy adults. We measured brain
      activity prior to movement during a bimanual load-lifting task, designed to
      elicit anticipatory adjustments in a restricted and well-defined set of
      musculature in the arm. Electroencephalography and magnetoencephalography brain
      measurements were obtained from eleven participants while they performed a
      bimanual load-lifting task that required precise inter-limb coordination.
      Anticipatory biceps brachii inhibition in the loaded arm was associated with a
      robust desynchronization of the beta rhythm. Beamforming analyses localized beta
      band responses to the parietal lobules, pre- and post-central gyri, middle and
      medial frontal gyri, basal ganglia and thalamus. The current study shows that
      premovement brain activity in a bimanual load-lifting task can be imaged with
      magnetoencephalography. Future experiments will partition out brain activity
      associated with anticipatory postural adjustments and volitional movements. The
      experimental paradigm will also be useful in the study of motor function in
      patients with developmental or degenerative disorders.

PMID- 21076823
TI  - MR findings of primary bone lymphoma in a 15-year-old girl: emphasis on diffusion
      weighted imaging.
AB  - We report a case of primary bone lymphoma (PBL) in a 15-year-old girl assessed by
      MR imaging with diffusion-weighted imaging (DWI). DWI has been shown to help
      characterize the cellularity of solid tumors and this case correlates well with
      previous data.

PMID- 21076825
TI  - Rupture of the left mainstem bronchus following endotracheal intubation in a
      neonate.
AB  - Tracheobronchial rupture is a rare diagnosis with very high associated mortality
      in the neonatal population. Our case demonstrates the opportunity to diagnose
      this entity in a neonate via CT and introduces the utility of virtual
      bronchoscopy in clinical scenarios that preclude traditional bronchoscopy.

PMID- 21076824
TI  - Asymptomatic leukemic-cell infiltration of the pancreas: US findings.
AB  - Pancreatic infiltration of leukemic cells is a very rare manifestation at the
      onset of acute lymphoblastic leukemia (ALL) in childhood. Pancreatic enlargement
      in this situation is unusual and pancreatic involvement is often associated with
      biliary obstruction, cholestasis and pancreatitis. We report a 3-month-old girl
      who presented with asymptomatic leukemic infiltration of the pancreas,
      demonstrated by US with heterogeneous pancreatic enlargement associated with
      multiple hypoechogenic lesions, without cholestasis. Although these
      manifestations are rare, ALL should be considered a cause of pancreatic
      enlargement.

PMID- 21076826
TI  - Raine syndrome: expanding the radiological spectrum.
AB  - We describe ante- and postnatal imaging of a 1-year-old otherwise healthy girl
      with Raine syndrome. She presented with neonatal respiratory distress related to
      a pyriform aperture stenosis, which was diagnosed on CT. Signs of
      chondrodysplasia punctata, sagittal vertebral clefting and intervertebral disc
      and renal calcifications were also found on imaging. This new case confirms that
      Raine syndrome is not always lethal. The overlapping imaging signs with
      chondrodysplasia punctata and the disseminated calcifications give new insights
      into its pathophysiology.

PMID- 21076828
TI  - Development of a successful antitumor therapeutic model combining in vivo
      dendritic cell vaccination with tumor irradiation and intratumoral GM-CSF
      delivery.
AB  - Vaccination of dendritic cells (DC) combined with GM-CSF secreting tumor cells
      has shown good therapeutic efficacy in several tumor models. Nevertheless, the
      engineering of GM-CSF secreting tumor cell line could represent a tedious step
      limiting its application for treatment in patients. We therefore developed in
      rats, an "all in vivo" strategy of combined vaccination using an in vivo local
      irradiation of the tumor as a source of tumor antigens for DC vaccines and an
      exogenous source of GM-CSF. We report here that supplying recombinant mGM-CSF by
      local injections or surgical implantation of osmotic pumps did not allow
      reproducing the therapeutic efficacy observed with in vitro prepared combined
      vaccines. To bypass this limitation possibly due to the short half-life of
      recombinant GM-CSF, we have generated adeno-associated virus coding for mGM-CSF
      and tested their efficacy to transduce tumor cells in vitro and in vivo. The in
      vivo vaccines combining local irradiation and AAV2/1-mGM-CSF vectors showed high
      therapeutic efficacy allowing to cure 60% of the rats with pre-implanted tumors,
      as previously observed with in vitro prepared vaccines. Same efficacy has been
      observed with a second generation of vaccines combining DC, local tumor
      irradiation, and the controlled supply of recombinant mGM-CSF in poloxamer 407, a
      biocompatible thermoreversible hydrogel. By generating a successful "all in vivo"
      vaccination protocol combining tumor radiotherapy with DC vaccines and a
      straightforward supply of GM-CSF, we have developed a therapeutic strategy easily
      translatable to clinic that could become accessible to a much bigger number of
      cancer patients.

PMID- 21076827
TI  - Monitoring anti-interleukin 6 receptor antibody treatment for rheumatoid
      arthritis by quantitative magnetic resonance imaging of the hand and power
      Doppler ultrasonography of the finger.
AB  - OBJECTIVES: To compare quantitative magnetic resonance imaging (MRI) and power
      Doppler ultrasonography (PDUS) with conventional measures of disease activity in
      rheumatoid arthritis (RA) patients treated with the anti-interleukin 6 (anti-IL
      6) receptor antibody tocilizumab in terms of responsiveness at a few months to
      disease activity and ability to predict structural damage at 1 year. METHODS: A
      cohort of patients with RA (n = 29) was evaluated clinically including disease
      activity score 28 (DAS28) and by semiquantitative (SQ-) and quantitative (Q-)
      PDUS (bilateral metacarpophalangeal joints) and MRI (one hand and wrist) at
      initiation of treatment with anti-IL 6 receptor antibody agents and after 2 and 5
      months. Conventional radiography for both hands and wrists was performed at
      baseline and at 12 months. Responsiveness was assessed by standardized response
      means (SRM). Areas under the curve (AUC) for measures at baseline, 2 and 5 months
      were correlated with structural damage at 1 year. RESULTS: Among the laboratory
      and clinical parameters, DAS28-ESR was the most responsive with a large effect
      size of SRM. Structural damage progressions for radiography and MR erosion were
      correlated with AUC of MR bone erosion and Q-PDUS, respectively. CONCLUSIONS: In
      the evaluation of disease activity in RA patients in the first few months after
      starting anti-IL 6 receptor antibody tocilizumab treatment, the semiquantitative
      MR bone erosion score of the hand and quantitative value for power Doppler signal
      in the finger joint were both responsive and predictive of structural damage
      progression at 1 year.

PMID- 21076830
TI  - Existence and stability of steady states of a reaction convection diffusion
      equation modeling microtubule formation.
AB  - We generalize the Dogterom-Leibler model for microtubule dynamics (Dogterom and
      Leibler in Phys Rev Lett 70(9):1347-1350, 1993) to the case where the rates of
      elongation as well as the lifetimes of the elongating shortening phases are a
      function of GTP-tubulin concentration. We analyze also the effect of nucleation
      rate in the form of a damping term which leads to new steady-states. For this
      model, we study existence and stability of steady states satisfying the boundary
      conditions at x=0. Our stability analysis introduces numerical and analytical
      Evans function computations as a new mathematical tool in the study of
      microtubule dynamics.

PMID- 21076829
TI  - Selective sweeps for recessive alleles and for other modes of dominance.
AB  - A selective sweep describes the reduction of linked genetic variation due to
      strong positive selection. If s is the fitness advantage of a homozygote for the
      beneficial allele and h its dominance coefficient, it is usually assumed that
      h=1/2, i.e. the beneficial allele is co-dominant. We complement existing theory
      for selective sweeps by assuming that h is any value in [0, 1]. We show that
      genetic diversity patterns under selective sweeps with strength s and dominance 0
      < h < 1 are similar to co-dominant sweeps with selection strength 2hs. Moreover,
      we focus on the case h=0 of a completely recessive beneficial allele. We find
      that the length of the sweep, i.e. the time from occurrence until fixation of the
      beneficial allele, is of the order of ?(N/s) generations, if N is the population
      size. Simulations as well as our results show that genetic diversity patterns in
      the recessive case h=0 greatly differ from all other cases.

PMID- 21076831
TI  - Evolutionary branching of a magic trait.
AB  - We study the adaptive dynamics of a so-called magic trait, which is under natural
      selection and which also serves as a cue for assortative mating. We derive
      general results on the monomorphic evolutionary singularities. Next, we study the
      long-term evolution of single-locus genetic polymorphisms under various strengths
      of assortativity in a version of Levene's soft-selection model, where natural
      selection favours different values of a continuous trait within two habitats. If
      adaptive dynamics leads to a polymorphism with sufficiently different alleles,
      then the corresponding homozygotes cease to interbreed so that sympatric
      speciation occurs.

PMID- 21076832
TI  - Sustained oscillations for density dependent Markov processes.
AB  - Simulations of models of epidemics, biochemical systems, and other bio-systems
      show that when deterministic models yield damped oscillations, stochastic
      counterparts show sustained oscillations at an amplitude well above the expected
      noise level. A characterization of damped oscillations in terms of the local
      linear structure of the associated dynamics is well known, but in general there
      remains the problem of identifying the stochastic process which is observed in
      stochastic simulations. Here we show that in a general limiting sense the
      stochastic path describes a circular motion modulated by a slowly varying
      Ornstein-Uhlenbeck process. Numerical examples are shown for the Volterra
      predator-prey model, Sel'kov's model for glycolysis, and a damped linear
      oscillator.

PMID- 21076833
TI  - On selection dynamics for competitive interactions.
AB  - In this paper, we are interested in an integro-differential model that describe
      the evolution of a population structured with respect to a continuous trait.
      Under some assumption, we are able to find an entropy for the system, and show
      that some steady solutions are globally stable. The stability conditions we find
      are coherent with those of Adaptive Dynamics.

PMID- 21076834
TI  - Determination of cAMP in plant cells by a modified enzyme immunoassay method.
AB  - Presently, there is no doubt about the functioning of the adenylate cyclase
      signaling system in plants, but the role of this system in various physiological
      biochemical processes has been investigated insufficiently. Cyclic adenosine
      monophosphate (cAMP), the key component produced by adenylate cyclase, whose
      concentrations in plant cells vary rather widely, is the indicator of functional
      activity for this signaling way. In the latter case, in the process of
      determination of concentrations of this messenger, one encounters difficulties
      related to insufficient sensitivity of the methods most frequently applied. In
      this connection, the proposed mechanism is a modification of the method of the
      enzyme immunoassay (EIA), which is based on immediate measurement of cAMP
      concentrations in the sample with the use of antibodies. This modification allows
      us to determine the concentrations of cAMP with the precision of 5 pM, which
      exceeds the sensitivity of other methods by approximately 10 times. The
      specificity of the assay has been confirmed by other two independent tests--the
      capillary electrophoresis and the nuclear magnetic resonance (NMR). It has also
      been compared to the data obtained with the use of the commercial kit from Sigma
      Aldrich. The modification has been tested on such plant objects as in vitro
      potato plants, and suspension cells of potato and Arabidopsis.

PMID- 21076835
TI  - High-level accumulation of recombinant miraculin protein in transgenic tomatoes
      expressing a synthetic miraculin gene with optimized codon usage terminated by
      the native miraculin terminator.
AB  - In our previous study, a transgenic tomato line that expressed the MIR gene under
      control of the cauliflower mosaic virus 35S promoter and the nopaline synthase
      terminator (tNOS) produced the taste-modifying protein miraculin (MIR). However,
      the concentration of MIR in the tomatoes was lower than that in the MIR gene's
      native miracle fruit. To increase MIR production, the native MIR terminator
      (tMIR) was used and a synthetic gene encoding MIR protein (sMIR) was designed to
      optimize its codon usage for tomato. Four different combinations of these genes
      and terminators (MIR-tNOS, MIR-tMIR, sMIR-tNOS and sMIR-tMIR) were constructed
      and used for transformation. The average MIR concentrations in MIR-tNOS, MIR
      tMIR, sMIR-tNOS and sMIR-tMIR fruits were 131, 197, 128 and 287 MUg/g fresh
      weight, respectively. The MIR concentrations using tMIR were higher than those
      using tNOS. The highest MIR accumulation was detected in sMIR-tMIR fruits. On the
      other hand, the MIR concentration was largely unaffected by sMIR-tNOS. The
      expression levels of both MIR and sMIR mRNAs terminated by tMIR tended to be
      higher than those terminated by tNOS. Read-through mRNA transcripts terminated by
      tNOS were much longer than those terminated by tMIR. These results suggest that
      tMIR enhances mRNA expression and permits the multiplier effect of optimized
      codon usage.

PMID- 21076836
TI  - Comparison of predictive methods and biological validation for qPCR reference
      genes in sunflower leaf senescence transcript analysis.
AB  - The selection and validation of reference genes constitute a key point for gene
      expression analysis based on qPCR, requiring efficient normalization approaches.
      In this work, the expression profiles of eight genes were evaluated to identify
      novel reference genes for transcriptional studies associated to the senescence
      process in sunflower. Three alternative strategies were applied for the
      evaluation of gene expression stability in leaves of different ages and exposed
      to different treatments affecting the senescence process: algorithms implemented
      in geNorm, BestKeeper software, and the fitting of a statistical linear mixed
      model (LMModel). The results show that geNorm suggested the use of all combined
      genes, although identifying alpha-TUB1 as the most stable expressing gene.
      BestKeeper revealed alpha-TUB and beta-TUB as stable genes, scoring beta-TUB as
      the most stable one. The statistical LMModel identified alpha-TUB, actin, PEP,
      and EF-1alpha as stable genes in this order. The model-based approximation allows
      not only the estimation of systematic changes in gene expression, but also the
      identification of sources of random variation through the estimation of variance
      components, considering the experimental design applied. Validation of alpha-TUB
      and EF-1alpha as reference genes for expression studies of three sunflower
      senescence associated genes showed that the first one was more stable for the
      assayed conditions. We conclude that, when biological replicates are available,
      LMModel allows a more reliable selection under the assayed conditions. This study
      represents the first analysis of identification and validation of genuine
      reference genes for use as internal control in qPCR expression studies in
      sunflower, experimentally validated throughout six different controlled leaf
      senescence conditions.

PMID- 21076837
TI  - Feasibility of using gene expression analysis to study canine soft tissue
      sarcomas.
AB  - The prognosis given for canine soft tissue sarcomas (STSs) is based primarily on
      histopathologic grade. The decision to administer adjuvant chemotherapy is
      difficult since less than half of patients with high-grade STSs develop
      metastatic disease. We hypothesize that there is a gene signature that will
      improve our ability to predict development of metastatic disease in STS patients.
      The objective of this study was to determine the feasibility of using cDNA
      microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene
      expression patterns in metastatic versus nonmetastatic canine STSs, given the
      inherent heterogeneity of this group of tumors. Five STSs from dogs with
      metastatic disease were evaluated in comparison to eight STSs from dogs without
      metastasis. Tumor RNA was extracted, processed, and labeled for application to
      the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using
      D-Chip software and data analysis was performed with JMP/Genomics. Differential
      gene expression was validated using qRT-PCR. Over 200 genes were differentially
      expressed at a false discovery rate of 5%. Differential gene expression was
      validated for five genes upregulated in metastatic tumors. Quantitative RT-PCR
      confirmed increased relative expression of all five genes of interest in the
      metastatic STSs. Our results demonstrate that microarray and qRT-PCR are feasible
      methods for comparing gene signatures in canine STSs. Further evaluation of the
      differences between gene expression in metastatic STSs and in nonmetastatic STSs
      is likely to identify genes that are important in the development of metastatic
      disease and improve our ability to prognosticate for individual patients.

PMID- 21076838
TI  - CD11c-expressing cells reside in the juxtavascular parenchyma and extend
      processes into the glia limitans of the mouse nervous system.
AB  - Recent studies demonstrated that primary immune responses can be induced within
      the brain depending on vessel-associated cells expressing markers of dendritic
      cells (DC). Using mice transcribing the green fluorescent protein (GFP) under the
      promoter of the DC marker CD11c, we determined the distribution, phenotype, and
      source of CD11c+ cells in non-diseased brains. Predilection areas of multiple
      sclerosis (MS) lesions (periventricular area, adjacent fibre tracts, and optical
      nerve) were preferentially populated by CD11c+ cells. Most CD11c+ cells were
      located within the juxtavascular parenchyma rather than the perivascular spaces.
      Virtually all CD11c+ cells co-expressed ionized calcium-binding adaptor molecule
      1 (IBA-1), CD11b, while detectable levels of major histocompatibility complex II
      (MHC-II) in non-diseased mice was restricted to CD11c+ cells of the choroid
      plexus. Cellular processes project into the glia limitans which may allow
      transport and/or presentation of intraparenchymal antigens to extravasated T
      cells in perivascular spaces. In chimeric mice bearing CD11c-GFP bone marrow,
      fluorescent cells appeared in the CNS between 8 and 12 weeks after
      transplantation. In organotypic slice cultures from CD11c-GFP mice, the number of
      fluorescent cells strongly increased within 72 h. Strikingly, using anti-CD209,
      an established marker for human DC, a similar population was detected in human
      brains. Thus, we show for the first time that CD11c+ cells can not only be
      recruited from the blood into the parenchyma, but also develop from an
      intraneural precursor in situ. Dysbalance in their recruitment/development may be
      an initial step in the pathogenesis of chronic (autoimmune) neuroinflammatory
      diseases such as MS.

PMID- 21076841
TI  - Carotid dissection in mitochondrial encephalomyopathy with lactic acidosis and
      stroke-like episodes.

PMID- 21076839
TI  - CD10-bearing fibroblasts may inhibit skin inflammation by down-modulating
      substance P.
AB  - Substance P (SP) is a multipotent neuropeptide that affects the proliferation,
      activation and motility of keratinocytes and fibroblasts (Fbs). SP in pulmonary
      and synovial cells is degraded by CD10, a 90- to 110-kDa cell surface zinc
      dependent metalloprotease. However, the expression and function of CD10 in human
      dermal Fbs have not yet been investigated in vivo and in vitro specifically with
      reference to SP. Our immunohistologic study revealed moderate to strong
      fibroblastic CD10 expression in the majority of psoriasis vulgaris (16/16),
      chronic eczema (15/16), lichen planus (18/20) and atopic dermatitis (4/5).
      Keratinocytes showed no CD10 expression in vivo and in vitro. Cultured Fbs
      constitutively expressed CD10 and SP. CD10 expression was augmented by external
      interleukin (IL)-1beta and IL-22, but not by IL-8 and IL-17A in Fbs. SP
      production was enhanced in CD10 knockdown-Fbs (CD10ND-Fbs) compared with control
      Fbs. In the presence of IL-1beta or IL-22, the enhancement of SP production was
      more prominent in CD10ND-Fbs than in control-Fbs, suggesting the down-modulating
      activity of CD10 on SP in cytokine-mediated inflammation. In conclusion,
      fibroblastic CD10 expression may down-regulate skin inflammation by degrading SP
      or reducing its level in the dermal microenvironment.

PMID- 21076842
TI  - Muscle metaboreflex activation by static exercise dilates pupil in humans.
AB  - We examined a hypothesis that static exercise and activation of sympathetic
      activation by metabolically sensitive skeletal muscle afferents (metaboreflex)
      influence the sympathetic nervous activity modulating pupil diameter. Nine
      subjects performed 2 min isometric handgrip exercise at 30% maximal voluntary
      contraction, which was followed by either 2 min of postexercise muscle ischemia
      (PEMI) in the forearm or no PEMI (control trial). The pupil diameter and mean
      blood pressure (MAP) increased significantly from rest during exercise in PEMI
      and control trials (5 +/- 1 and 7 +/- 1% in diameter; 13 +/- 2 and 12 +/- 2 mmHg
      in MAP, respectively). These increases in the diameter and MAP were maintained
      during PEMI (7 +/- 2% and 9 +/- 2 mmHg) but not during the recovery period in the
      control trial (3 +/- 2% and 1 +/- 2 mmHg). These results demonstrate that static
      handgrip exercise increases the pupil diameter, and this increase is partly due
      to the activation of metaboreflex in humans.

PMID- 21076843
TI  - Downregulation of reversion-inducing-cysteine-rich protein with Kazal motifs
      (RECK) is associated with enhanced expression of matrix metalloproteinases and
      cholangiocarcinoma metastases.
AB  - BACKGROUND: Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has
      been implicated in the attenuation of tumor metastasis by negatively regulating
      metalloproteinase (MMP) levels. RECK gene expression is downregulated in many
      solid tumors, with this downregulation being associated with poor prognosis. This
      study evaluated the role of RECK in cholangiocarcinoma (CCA). METHODS: The
      expression of RECK, MMP-2, and MMP-9 in paraffin sections of hamster and human
      CCA specimens was analyzed by immunohistochemistry. Functional analysis of RECK
      was performed in RECK small interfering (si) RNA knockdown CCA cell lines. The
      effect of aspirin on RECK status and function was evaluated using Western
      blotting, gelatin zymography, invasion and proliferation assays, and
      PhosphoELISArray analysis of Ras downstream mediators. RESULTS: Hamster tissues
      showed high RECK expression in hyperplastic biliary duct epithelia, low RECK
      expression in precancerous lesions, and no RECK expression in CCA. In human
      specimens, RECK was highly expressed in normal biliary cells, whereas
      intrahepatic CCA showed low levels of expression. Downregulation of RECK was
      correlated with tumor metastasis (P < 0.01) and shorter patient survival (P <
      0.02). RECK expression levels were inversely correlated with MMP-2 and MMP-9
      expression (P < 0.05). SiRNA RECK-depleted M139 CCA cells exhibited increased MMP
      2/-9 gelatinase activities and invasiveness. Aspirin (500 MUM) demonstrated
      myriad effects in human CCA cell lines, including growth suppression, reduced
      phosphorylation of Akt/Erk/c-Jun, elevation of RECK expression, inhibition of MMP
      2/MMP-9 activity, and enhanced invasiveness. CONCLUSIONS: RECK functions as a
      metastasis suppressor in CCA; upregulation of RECK expression could provide a
      potential therapy to improve the prognosis of this type of cancer.

PMID- 21076844
TI  - Modified total en bloc spondylectomy in thoracic vertebra tumour.
AB  - Total en bloc spondylectomy (TES) for vertebral tumour was previously reported by
      Tomita through a single posterior approach using a T-saw. A modified total en
      bloc spondylectomy (MTES) technique is reported in the present study. The disc
      puncture needle with a sleeve was used to obliquely puncture from the posterior
      to the anterior direction. A T-saw was inserted through the sleeve and led out to
      the operator's side by the leading clamp. The disc was partially cut with the saw
      from its medial to lateral aspect. After a spinal fixation rod was applied on the
      operator's side, the residual discs on the opposite side were cut as described
      above. Six patients with thoracic vertebral tumours were operated on using the
      MTES technique. Five patients showed improvement in their neurological deficits
      postoperatively. There was no evidence of tumour recurrence at the final follow
      up. The MTES is technically feasible with improved practicality and safety.

PMID- 21076845
TI  - Complete nucleotide sequence of a potato isolate of strain group C of Potato
      virus Y from 1938.
AB  - The complete genomic sequence of an isolate (PRI-509) of the C strain of Potato
      virus Y (PVY(C)), which was originally isolated from potato in 1938, was
      elucidated. The genomic RNA of PRI-509 consists of 9699 nucleotides, with the
      capacity to encode a polyprotein of 3061 amino acids with a molecular mass of 337
      kDa.This is the first full-length sequence of a PVY (C) isolate from potato that
      belongs to the C1 phylogenetic subgroup, which was previously thought to
      exclusively contain non-potato isolates.

PMID- 21076846
TI  - The complete genome sequence of a Passion fruit woodiness virus isolate from
      Australia determined using deep sequencing, and its relationship to other
      potyviruses.
AB  - The complete genome sequence (9,858 nucleotides) of the Passion fruit woodiness
      virus isolate MU-2 was determined using Illumina sequencing. The large open
      reading frame (ORF) encodes a polyprotein containing 3,086 amino acids, with an
      AUG start codon and UAA stop codon. The polyprotein yielded 11 proteins (P1, HC
      Pro, P3, PIPO, 6K1, CI, 6K2, NIa-VPg, NIa-Pro, NIb and CP). Putative cleavage
      sites between them were identified by sequence comparison to those of other known
      potyviruses. Accuracy of the genome sequence information was provided by 42-1691
      fold sequence coverage, and viral RNA accounted for 7.38% of total polyadenylated
      RNA from the host plant.

PMID- 21076848
TI  - Tourette's disorder and other tic disorders in DSM-5: a comment.
AB  - Classification of tic disorders will be revised in the forthcoming edition of the
      Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). We do not
      support the suggestion to move tic disorders to "Anxiety and Obsessive-Compulsive
      Disorders", if the section "Disorders Usually First Diagnosed in Infancy,
      Childhood, or Adolescence" is not retained. Other than that, most proposed
      changes of the criteria for tic disorders contain a number of welcome
      improvements, e.g., the more unified definition of tics including the removal of
      the term "stereotyped" and the better capture of the temporal pattern of tics
      (e.g., removal of the maximum 3 months criterion for a tic-free period in chronic
      tic disorders). But, unfortunately there are some inconsistencies in detail,
      e.g., the unification of diagnostic criteria for tic disorders had not been
      consistently pursued in transient tic disorder. In sum, the proposed DSM-5
      criteria could be seen as an important step forward particularly in clinical
      routine. However, continued research is needed to justify the existing and
      proposed classification of tic disorders as well as to better clarify what other
      changes should be made in the DSM-5 and beyond.

PMID- 21076847
TI  - The peculiar heme pocket of the 2/2 hemoglobin of cold-adapted Pseudoalteromonas
      haloplanktis TAC125.
AB  - The genome of the cold-adapted bacterium Pseudoalteromonas haloplanktis TAC125
      contains multiple genes encoding three distinct monomeric hemoglobins exhibiting
      a 2/2 alpha-helical fold. In the present work, one of these hemoglobins is
      studied by resonance Raman, electronic absorption and electronic paramagnetic
      resonance spectroscopies, kinetic measurements, and different bioinformatic
      approaches. It is the first cold-adapted bacterial hemoglobin to be
      characterized. The results indicate that this protein belongs to the 2/2
      hemoglobin family, Group II, characterized by the presence of a tryptophanyl
      residue on the bottom of the heme distal pocket in position G8 and two tyrosyl
      residues (TyrCD1 and TyrB10). However, unlike other bacterial hemoglobins, the
      ferric state, in addition to the aquo hexacoordinated high-spin form, shows
      multiple hexacoordinated low-spin forms, where either TyrCD1 or TyrB10 can likely
      coordinate the iron. This is the first example in which both TyrCD1 and TyrB10
      are proposed to be the residues that are alternatively involved in heme
      hexacoordination by endogenous ligands.

PMID- 21076849
TI  - Methicillin-resistant Staphylococcus-aureus-associated glomerulonephritis on the
      decline: decreased incidence since the 1990s.
AB  - We believe that bacterial-infection-associated glomerulonephritis (GN), so-called
      methicillin-resistant Staphylococcus aureus (MRSA)-GN, was exterminated in Japan.
      The control of bacterial infection is the most important part of infection
      associated GN. In 1990s Japan, hospital-associated MRSA (HA-MRSA) caused MRSA-GN
      outbreaks. On the other hand, MRSA-GN incidence has been quite limited since
      2000. This epidemiological transition suggests that antibacterial therapies and
      health programs for HA-MRSA infection in Japan were effective against MRSA-GN.
      Moreover, it appears that staphylococcal superantigens act in the pathogenesis of
      GN. The change of superantigen production might have influenced to the
      disappearance of MRSA-GN. If HA-MRSA-producing superantigen outbreaks occur in
      developing countries, our experience in Japan can provide guiding principles for
      preventing and eradicating GN.

PMID- 21076850
TI  - Evaluating comorbidities in total hip and knee arthroplasty: available
      instruments.
AB  - Each year millions of patients are treated for joint pain with total joint
      arthroplasty, and the numbers are expected to rise. Comorbid disease is known to
      influence the outcome of total joint arthroplasty, and its documentation is
      therefore of utmost importance in clinical evaluation of the individual patient
      as well as in research. In this paper, we examine the various methods for
      obtaining and assessing comorbidity information for patients undergoing joint
      replacement. Multiple instruments are reliable and validated for this purpose,
      such as the Charlson Index, Index of Coexistent Disease, and the Functional
      Comorbidity Index. In orthopedic studies, the Charnley classification and the
      American Society of Anesthesiologists physical function score (ASA) are widely
      used. We recommend that a well-documented comorbidity index that incorporates
      some aspect of mental health is used along with other appropriate instruments to
      objectively assess the preoperative status of the patient.

PMID- 21076851
TI  - Translation initiation: variations in the mechanism can be anticipated.
AB  - Translation initiation is a critical step in protein synthesis. Previously, two
      major mechanisms of initiation were considered as essential: prokaryotic, based
      on SD interaction; and eukaryotic, requiring cap structure and ribosomal
      scanning. Although discovered decades ago, cap-independent translation has
      recently been acknowledged as a widely spread mechanism in viruses, which may
      take place in some cellular mRNA translations. Moreover, it has become evident
      that translation can be initiated on the leaderless mRNA in all three domains of
      life. New findings demonstrate that other distinguishable types of initiation
      exist, including SD-independent in Bacteria and Archaea, and various
      modifications of 5' end-dependent and internal initiation mechanisms in Eukarya.
      Since translation initiation has developed through the loss, acquisition, and
      modification of functional elements, all of which have been elevated by
      competition with viral translation in a large number of organisms of different
      complexity, more variation in initiation mechanisms can be anticipated.

PMID- 21076853
TI  - mTORC1 activation in childhood ependymoma and response to sirolimus.
AB  - Recurrent ependymomas are considered rarely responsive to chemotherapy and often
      have a dismal prognosis after tumor progression. Below is a brief report of a 6
      year old child with a multiply progressive ependymoma whose tumor had a near
      complete response to sirolimus that was durable for 18 months.
      Immunohistochemistry for phosphorylated S6, which has been reported to be
      associated with tumor sensitivity to mTORC1 inhibitors, was positive in this
      patient's tumor.

PMID- 21076852
TI  - The role of nitric oxide during healing of trauma to the skeletal muscle.
AB  - INTRODUCTION: The role of NO in muscle injury is not clear. METHODS: We examined
      the involvement of the NO system in the development of muscle damage in an
      experimental model of crush injury. The animals were divided into four groups:
      (1) control (CO), (2) sham trauma, (3) trauma, (4) trauma + L -NAME, in two
      experimental phases, 24 h and 7 days after injury. RESULTS: Twenty-four hours
      post-trauma, the crushed muscle was characterized by an intense inflammatory
      reaction. These changes were accompanied by increased oxidative damage, increased
      cytokine mRNA transcription, NF-kappaB binding ability and TGF-beta growth factor
      expression in the gastrocnemius muscle. Treatment with L: -NAME markedly
      decreased these histological and molecular abnormalities at 24 h. However, at 7
      days post-trauma, increased collagen formation was observed in the L: -NAME
      group. DISCUSSION: These findings indicate that NO is involved in the balance
      between fibrosis and healing with regeneration.

PMID- 21076854
TI  - Mesenteric vascular remodeling in hyperhomocysteinemia.
AB  - Remodeling by its very nature implies synthesis and degradation of extracellular
      matrix components (such as elastin, collagen, and connexins). Most of the
      vascular matrix metalloproteinase (MMP) are latent because of the presence of
      constitutive nitric oxide (NO). However, during oxidative stress peroxinitrite
      (ONOO-) activates the latent MMPs and instigates vascular remodeling.
      Interestingly, in mesenteric artery, homocysteine (Hcy) decreases the NO bio
      availability, and folic acid (FA, an Hcy-lowering agent) mitigates the Hcy
      mediated mesentery artery dysfunction. Dimethylarginine dimethylaminohydrolase-2
      (DDAH-2) and endothelial nitric oxide synthase (eNOS) increases NO production.
      The hypothesis was that the Hcy decreased NO bio-availability, in part,
      activating MMP, decreasing elastin, DDAH-2, eNOS and increased vasomotor response
      by increasing connexin. To test this hypothesis,the authors used 12-week-old
      C57BJ/L6 wild type (WT) and hyperhomocysteinemic (HHcy)-cystathione beta synthase
      heterozygote knockout (CBS+/-) mice. Blood pressure measurements were made by
      radio-telemetry. WT and MMP-9 knockout mice were administered with Hcy (0.67
      mg/ml in drinking water). Superior mesenteric artery and mesenteric arcade were
      analyzed with light and confocal microscopy. The protein expressions were
      measured by western blot analysis. The mRNA levels for MMP-9 were measured by RT
      PCR. The data showed decreased DDAH-2 and eNOS expressions in mesentery in CBS-/+
      mice compared with WT mice. Immuno-fluorescence and western blot results suggest
      increased MMP-9 and connexin-40 expression in mesenteric arcades of CBS-/+ mice
      compared with WT mice. The wall thickness of third-order mesenteric artery was
      increased in CBS-/+ mice compared to WT mice. Hcy treatment increased blood
      pressure in WT mice. Interestingly, in MMP-9 KO, Hcy did not increase blood
      pressure. These results may suggest that HHcy causes mesenteric artery remodeling
      and narrowing by activating MMP-9 and decreasing DDAH-2 and eNOS expressions,
      compromising the blood flow, instigating hypertension, and acute abdomen pain.

PMID- 21076856
TI  - Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and
      insulin-like growth factor I.
AB  - Insulin and parathyroid hormone (PTH) regulate glucose metabolism in bone cells.
      In order to differentiate between the effects of these hormones and to compare
      the potency of insulin with that of insulin-like growth factor (IGF) I, we
      treated rat bone-derived osteoblastic (PyMS) cells for different time periods and
      at different concentrations with insulin, IGF I, or PTH, and measured [1-(14)C]-2
      deoxy-D-glucose (2DG) uptake and incorporation of D-[U-(14)C] glucose into
      glycogen. 2DG uptake was Na-independent with an apparent affinity constant (K
      (M)) of ~2 mmol/l. Expression of the high affinity glucose transporters (GLUT),
      GLUT1 and GLUT3 but not of GLUT4, was found by Northern and Western analysis.
      Similar to the findings with primary rat osteoblasts, but distinct from those in
      rat fibroblasts, 2DG uptake and glycogen synthesis were increased in this cell
      line after exposure to low concentrations (0.1 nmol/l and above) of PTH. IGF I at
      low doses (0.3 nmol/l and above) or insulin at higher doses (1 nmol/l and above)
      stimulated 2DG uptake and [(3)H] thymidine incorporation into DNA. 2DG transport
      was enhanced already after 30 min of IGF I treatment whereas the effect of PTH
      became significant after 6 h. It is concluded that IGF I rather than insulin may
      be a physiological regulator of 2DG transport and glycogen synthesis in
      osteoblasts.

PMID- 21076855
TI  - Molecular cloning and characterization of twist gene in Bombyx mori.
AB  - The twist genes are an evolutionarily conserved group of regulatory basic helix
      loop-helix (bHLH) transcription factors. In present study, the twist gene was
      firstly cloned from Bombyx mori and was designated as BmTwist. Sequence analysis
      showed that BmTwist cDNA contains a 798 bp open reading frame, encoding a peptide
      of 266 amino acid residues. Sequence alignment showed that BmTwist protein shared
      extensive homology with other invertebrate Twist proteins in bHLH motif. RT-PCR
      and western blot analyses revealed that BmTwist expressed in all developmental
      stages of B. mori larvae various larval tissues. Here the authors also presented
      the results of prokaryotic expression, purification, and polyclonal antibody
      production of the BmTwist protein. Immunofluorescence of BmTwist in BmN cells
      using the antibodies showed that BmTwist protein was located in both the nucleus
      and cytoplasm. Furthermore, using B. mori nuclear polyhedrosis virus (BmNPV)
      baculovirus expression system, the authors expressed a recombinant twist protein
      in BmN cell line. The obtained results, especially the preparation of polyclonal
      antibodies against BmTwist, will greatly facilitate further studies to explore
      biological functions of BmTwist protein such as identifying its potential binding
      partners.

PMID- 21076857
TI  - The bioactivity and ion release of titanium-containing glass polyalkenoate
      cements for medical applications.
AB  - The ion release profiles and bioactivity of a series of Ti containing glass
      polyalkenoate cements. Characterization revealed each material to be amorphous
      with a T(g) in the region of 650-660 degrees C. The network connectivity
      decreased (1.83-1.35) with the addition of TiO(2) which was also evident with
      analysis by X-ray photoelectron spectroscopy. Ion release from cements were
      determined using atomic absorption spectroscopy for zinc (Zn(2+)), calcium
      (Ca(2+)), strontium (Sr(2+)), Silica (Si(4+)) and titanium (Ti(4+)). Ions such as
      Zn(2+) (0.1-2.0 mg/l), Ca(2+) (2.0-8.3 mg/l,) Sr(2+) (0.1-3.9 mg/l), and Si(4+)
      (14-90 mg/l) were tested over 1-30 days. No Ti(4+) release was detected.
      Simulated body fluid revealed a CaP surface layer on each cement while cell
      culture testing of cement liquid extracts with TW-Z (5 mol% TiO(2)) produced the
      highest cell viability (161%) after 30 days. Direct contact testing of discs
      resulted in a decrease in cell viability of the each cement tested.

PMID- 21076858
TI  - Two bootstrapping routines for obtaining imprecision estimates for nonparametric
      parameter distributions in nonlinear mixed effects models.
AB  - When parameter estimates are used in predictions or decisions, it is important to
      consider the magnitude of imprecision associated with the estimation. Such
      imprecision estimates are, however, presently lacking for nonparametric
      algorithms intended for nonlinear mixed effects models. The objective of this
      study was to develop resampling-based methods for estimating imprecision in
      nonparametric distribution (NPD) estimates obtained in NONMEM. A one-compartment
      PK model was used to simulate datasets for which the random effect of clearance
      conformed to a (i) normal (ii) bimodal and (iii) heavy-tailed underlying
      distributional shapes. Re-estimation was conducted assuming normality under FOCE,
      and NPDs were estimated sequential to this step. Imprecision in the NPD was then
      estimated by means of two different resampling procedures. The first (full)
      method relies on bootstrap sampling from the raw data and a re-estimation of both
      the preceding parametric (FOCE) and the nonparametric step. The second
      (simplified) method relies on bootstrap sampling of individual nonparametric
      probability distributions. Nonparametric 95% confidence intervals (95% CIs) were
      obtained and mean errors (MEs) of the 95% CI width were computed. Standard errors
      (SEs) of nonparametric population estimates were obtained using the simplified
      method and evaluated through 100 stochastic simulations followed by estimations
      (SSEs). Both methods were successfully implemented to provide imprecision
      estimates for NPDs. The imprecision estimates adequately reflected the reference
      imprecision in all distributional cases and regardless of the numbers of
      individuals in the original data. Relative MEs of the 95% CI width of CL marginal
      density when original data contained 200 individuals were equal to: (i) -22 and 
      12%, (ii) -22 and -9%, (iii) -13 and -5% for the full and simplified (n = 100),
      respectively. SEs derived from the simplified method were consistent with the
      ones obtained from 100 SSEs. In conclusion, two novel bootstrapping methods
      intended for nonparametric estimation methods are proposed. In addition of
      providing information about the precision of nonparametric parameter estimates,
      they can serve as diagnostic tools for the detection of misspecified parameter
      distributions.

PMID- 21076859
TI  - The changes of pulmonary blood flow in non-ventilated lung during one lung
      ventilation.
AB  - OBJECTIVE: A pulmonary artery catheter placement is necessary for intrapulmonary
      shunt fraction evaluation. The purpose of this study was to investigate the
      feasibility for detecting the changes of regional pulmonary blood flow in non
      ventilated lung by transesophageal echocardiography (TEE) during one-lung
      ventilation (OLV). METHODS: 22 adult patients for selective thoracic surgery were
      enrolled in the study. Doppler flow patterns in left upper pulmonary vein (LUPV)
      were obtained by TEE before switching to right OLV and every 5 min in 30 min OLV
      period. Systolic peak velocity (Vs), diastolic peak velocity (Vd) and velocity
      time integral (VTI) were measured respectively. RESULTS: The VTI of LUPV blood
      flow pattern decreased significantly 5 min after right OLV. The percent of
      changes in LUPV blood flow decreased rapidly by 78.4 and 67.7% at OLV 5 min and
      10 min, respectively. Then it slowly decreased by 60% at OLV 30 min. CONCLUSIONS:
      Provides an alternative method to measure the changes of pulmonary blood flow
      during OLV. The percent changes of regional pulmonary blood flow decreased
      immediately after OLV, and decreased by 60% at 30 min OLV.

PMID- 21076860
TI  - Perceived parental monitoring, adolescent disclosure, and adolescent depressive
      symptoms: a longitudinal examination.
AB  - Parental monitoring has long been stressed as an important parenting practice in
      reducing adolescents' susceptibility to depressive symptoms. Reviews have
      revealed, however, that measures of monitoring have been confounded with parental
      knowledge, and that the role of adolescent disclosure has been neglected. In the
      present study, adolescents (N = 2,941; 51.3% female) were surveyed each year from
      grades 9-12. To disentangle parenting factors, bidirectional associations among
      parental knowledge, adolescent disclosure, and parental monitoring (i.e.,
      solicitation and control) were examined. Higher parental knowledge was associated
      with lower adolescent depressive symptoms over time. Adolescent disclosure and
      parental control also predicted lower adolescent depressive symptoms indirectly
      through knowledge. Conversely, higher adolescent depressive symptoms predicted
      lower parental knowledge, adolescent disclosure, and parental solicitation over
      time, highlighting the bidirectional nature of associations among parenting
      factors and adolescent depressive symptoms. Importantly, these effects were
      invariant across gender and grade, suggesting that interventions can be broadly
      based.

PMID- 21076861
TI  - Neuronavigation increases the physiologic and behavioral effects of low-frequency
      rTMS of primary motor cortex in healthy subjects.
AB  - Low-frequency repetitive transcranial magnetic stimulation (rTMS) can exert local
      and inter-hemispheric neuromodulatory effects on cortical excitability. These
      physiologic effects can translate into changes in motor behavior, and may offer
      valuable therapeutic interventions in recovery from stroke. Neuronavigated TMS
      can maximize accurate and consistent targeting of a given cortical region, but is
      a lot more involved that conventional TMS. We aimed to assess whether
      neuronavigation enhances the physiologic and behavioral effects of low-frequency
      rTMS. Ten healthy subjects underwent two experimental sessions during which they
      received 1600 pulses of either navigated or non-navigated 1 Hz rTMS at 90% of the
      resting motor threshold (RMT) intensity over the motor cortical representation
      for left first dorsal interosseous (FDI) muscle. We compared the effects of
      navigated and non-navigated rTMS on motor-evoked potentials (MEPs) to single
      pulse TMS, intracortical inhibition (ICI) and intracortical facilitation (ICF) by
      paired-pulse TMS, and performance in various behavioral tasks (index finger
      tapping, simple reaction time and grip strength tasks). Following navigated rTMS,
      the amplitude of MEPs elicited from the contralateral (unstimulated) motor cortex
      was significantly increased, and was associated with an increase in ICF and a
      trend to decrease in ICI. In contrast, non-navigated rTMS elicited nonsignificant
      changes, most prominently ipsilateral to rTMS. Behaviorally, navigated rTMS
      significantly improved reaction time RT and pinch force with the hand ipsilateral
      to stimulation. Non-navigated rTMS lead to similar behavioral trends, although
      the effects did not reach significance. In summary, navigated rTMS leads to more
      robust modulation of the contralateral (unstimulated) hemisphere resulting in
      physiologic and behavioral effects. Our findings highlight the spatial
      specificity of inter-hemispheric TMS effects, illustrate the superiority of
      navigated rTMS for certain applications, and have implications for therapeutic
      applications of rTMS.

PMID- 21076863
TI  - Socioeconomic differences in survival among breast cancer patients in the
      Netherlands not explained by tumor size.
AB  - There seem to be socioeconomically differences in survival for females with
      breast cancer, usually associated with a higher stage of disease. However,
      differences within tumor size have not been studied. Aim of this study is to
      assess differences in survival according to socioeconomic status (SES),
      stratified for tumor size and stage at diagnosis, for females with breast cancer
      in the Netherlands. All females diagnosed with breast cancer (1995-2005) were
      selected from the Netherlands Cancer Registry. Patients were linked to a SES
      database according to postal code. A multivariable logistic regression was used
      to assess factors associated with SES. Overall survival (OS) and relative
      survival (RS) were calculated. Overall, 127,599 patients were included. Higher
      SES was associated with lower T-stage (P < 0.0001). A decreased survival (OS and
      RS) was found for patients with a lower SES. Also within different size groups,
      RS was different. Overall, 10-year OS for the high SES group was 65 and 58% for
      the low SES group (hazard ratio 1.1, P < 0.001) and RS was 79 versus 74%
      (relative excess risk, RER 1.2; P < 0.001). The socioeconomic differences
      remained statistically significant (P < 0.001) after adjustment for age, year of
      diagnosis, grade, TNM stage, and treatment. For the lowest SES group 777 deaths
      could be avoided. Socioeconomic differences in survival of breast cancer patients
      were observed in the Netherlands. Higher stage at diagnosis of patients with a
      lower SES only partly explains the decreased survival. Policies aimed at the
      reduction of socioeconomic health inequalities might be important to improve
      survival of breast cancer.

PMID- 21076864
TI  - Disparities in breast cancer characteristics and outcomes by race/ethnicity.
AB  - Disparities in breast cancer stage and mortality by race/ethnicity in the United
      States are persistent and well known. However, few studies have assessed
      differences across racial/ethnic subgroups of women broadly defined as Hispanic,
      Asian, or Pacific Islander, particularly using more recent data. Using data from
      17 population-based cancer registries in the Surveillance, Epidemiology, and End
      Results (SEER) program, we evaluated the relationships between race/ethnicity and
      breast cancer stage, hormone receptor status, treatment, and mortality. The
      cohort consisted of 229,594 women 40-79 years of age diagnosed with invasive
      breast carcinoma between January 2000 and December 2006, including 176,094 non
      Hispanic whites, 20,486 Blacks, 15,835 Hispanic whites, 14,951 Asians, 1,224
      Pacific Islanders, and 1,004 American Indians/Alaska Natives. With respect to
      statistically significant findings, American Indian/Alaska Native, Asian
      Indian/Pakistani, Black, Filipino, Hawaiian, Mexican, Puerto Rican, and Samoan
      women had 1.3-7.1-fold higher odds of presenting with stage IV breast cancer
      compared to non-Hispanic white women. Almost all groups were more likely to be
      diagnosed with estrogen receptor-negative/progesterone receptor-negative (ER-/PR
      ) disease with Black and Puerto Rican women having the highest odds ratios (2.4
      and 1.9-fold increases, respectively) compared to non-Hispanic whites. Lastly,
      Black, Hawaiian, Puerto Rican, and Samoan patients had 1.5-1.8-fold elevated
      risks of breast cancer-specific mortality. Breast cancer disparities persist by
      race/ethnicity, though there is substantial variation within subgroups of women
      broadly defined as Hispanic or Asian. Targeted, multi-pronged interventions that
      are culturally appropriate may be important means of reducing the magnitudes of
      these disparities.

PMID- 21076865
TI  - Acidification reversal in low mountain range streams of Germany.
AB  - This study evaluates the acidification status and trends in streams of forested
      mountain ranges in Germany in consequence of reduced anthropogenic deposition
      since the mid 1980s. The analysis is based on water quality data for 86 long-term
      monitored streams in the Ore Mountains, the Bavarian Forest, the Fichtelgebirge,
      the Harz Mountains, the Spessart, the Black Forest, the Thuringian Forest, and
      the Rheinisches Schiefergebirge of Germany and the Vosges of France. Within the
      observation period, which starts for the individual streams between 1980 and 2001
      and ends between 1990 and 2009, trends in chemical water quality were calculated
      with the Seasonal Mann Kendall Test. About 87% of the streams show significant (p
      < 0.05) negative trends in sulfate. The general reduction in acid deposition
      resulted in increased pH values (significant for 66% of the streams) and
      subsequently decreased base cation concentrations in the stream water (for
      calcium significant in 58% and magnesium 49% of the streams). Reaction products
      of acidification such as aluminum (significant for 50%) or manganese (significant
      for 69%) also decreased. Nitrate (52% with significant decrease) and chloride
      (38% with significant increase) have less pronounced trends and more variable
      spatial patterns. For the quotient of acidification, which is the ratio of the
      sum of base cations and the sum of acid anions, no clear trend is observed: in
      44% of the monitored streams values significantly decreased and in 23% values
      significantly increased. A notable observation is the increasing DOC
      concentration, which is significant for 55% of the observed streams.

PMID- 21076862
TI  - A comprehensive model for mental health tobacco recovery in new jersey.
AB  - Despite the high prevalence of tobacco use, disproportionate tobacco consumption,
      and excess morbidity and mortality, smokers with mental illness have reduced
      access to tobacco dependence treatment across the health care spectrum. We have
      developed a comprehensive model for Mental Health Tobacco Recovery in New Jersey
      (MHTR-NJ) that has the overarching goal of improving tobacco cessation for
      smokers with serious mental illness. Important steps involve engaging patients,
      professionals and the community to increase understanding that addressing tobacco
      use is important. In addition to increasing demand for tobacco treatment
      services, we must educate mental health professionals in evidence-based
      treatments so that patients can seek help in their usual behavioral health care
      setting. Peer services that offer hope and support to smokers are essential. Each
      of the policy or cessation initiatives described address the two core goals of
      this model: to increase demand for tobacco cessation services for mentally ill
      smokers and to help more smokers with mental illness to quit. Each has been pilot
      tested for feasibility and/or effectiveness and revised with feedback from
      stakeholders. In this way this implementation model has brought together
      academics, clinicians, administrators and mental health consumers to develop
      tobacco programming and policy that has been tested in a real world environment
      and serves as a model for other states.

PMID- 21076866
TI  - The effects of residential proximity to bars on alcohol consumption.
AB  - A person's decision to drink alcohol is potentially influenced by both price and
      availability of alcohol in the local area. This study uses longitudinal data from
      1985 to 2001 to empirically assess the impact of distance from place of residence
      to bars on alcohol consumption in four large U.S. cities from 1985 to 2001.
      Density of bars within 0.5 km of a person's residence is associated with small
      increases in alcohol consumption as measured by: daily alcohol consumption (ml)
      drinks per week, and weekly consumption of beer, wine, and liquor. When person
      specific fixed effects are included, the relationship between alcohol consumption
      and the number of bars within a 0.5 km radius of the person's place of residence
      disappears. Tests for endogeneity of the number of bars within the immediate
      vicinity of respondents' homes fail to reject the null hypothesis that the number
      of bars is exogenous. We conclude that bar density in the area surrounding the
      individuals' homes has at most a very small positive effect on alcohol
      consumption.

PMID- 21076867
TI  - Effect of treadmill exercise on blood glucose, serum corticosterone levels and
      glucocorticoid receptor immunoreactivity in the hippocampus in chronic diabetic
      rats.
AB  - Abnormal excess of glucocorticoid is one of feature characteristics in type 2
      diabetes. In the present study, we investigated the effect of treadmill exercise
      at chronic diabetic stages on glucocorticoid receptor (GR) immunoreactivity in
      the hippocampal CA1 region and dentate gyrus, which are very vulnerable to
      diabetes. For this study, we used Zucker diabetic fatty (ZDF) rats and Zucker
      lean control (ZLC) rats. Twenty-three-week-old ZLC and ZDF rats were put on the
      treadmill with or without running for 7 weeks and sacrificed at 30 weeks of age.
      Treadmill exercise significantly decreased diabetes-induced blood glucose and
      serum corticosteroid levels although they did not drop to control levels. In
      sedentary ZLC rats, GR immunoreactivity was detected in pyramidal cells of the
      CA1 region as well as in granule cells of the dentate gyrus. In the sedentary ZDF
      rats, GR immunoreactivity was significantly increased in these regions. However,
      treadmill exercise significantly decreased GR immunoreactivity in these regions.
      These results indicate that treadmill exercise in chronic diabetic rats
      significantly decreased GR immunoreactivity in the hippocampal CA1 region and
      dentate gyrus, although blood glucose and serum corticosteroid levels did not
      fully recover to normal state.

PMID- 21076868
TI  - Modulation of sphingosine 1-phosphate and tyrosine hydroxylase in the stress
      induced anxiety.
AB  - Stress causes endocrinological changes and leads to induce anxiety. It was
      determined the anxiety and stress-related endocrinological changes through the
      observation of the level of glucocorticoid and sphingolipid metabolites in serum
      after stress. Immobilized stress and electric shock was applied to rats for 7
      days. This study investigated the induction of anxiety, changes of TH and pERK
      expression in cortex and amygdala after stress. Also it was determined the
      changes of glucocorticoid and anxiety when the rats were given stress after
      amygdala lesion. The stress-given rats spent a lesser percentage of time
      significantly in the open arm than the control rats. The elevated level of
      glucocorticoid after stress was suppressed in amygdala lesion group. The
      expression of TH in the amygdala was decreased, but the expression of TH was not
      changed in the cortex after stress. To investigate the changes in sphingolipid
      metabolites after stress, the levels of sphingosine and the phosphate form of
      sphingolipid (So-1-P) were analyzed in serum. The level of So-1-P was elevated
      after stress and anxiety was observed after the So-1-P infusion (100 pmol/10
      MUl/h, i.c.v., for 7 days). Continuous infusion of So-1-P for 7 days led to the
      significant decrease of TH expression in the amygdala. In conclusion, the results
      of this study indicate that the lesion of amygdala suppressed the stress-induced
      anxiety and elevation of glucocorticoid in serum. It was also observed that
      expression of TH in amygdala as well as increased levels of glucocorticoid in
      serum might be responsible biomarker, at least in part, of chronic stress. These
      results suggest that the elevation of So-1-P might be involved in induction of
      anxiety during stress by the modulation of dopaminergic system in amygdala.

PMID- 21076869
TI  - Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated
      with serum corticosterone and GABA in the mouse dentate gyrus.
AB  - Lemon balm, leaves of Melissa officinalis L., has been used for anti-anxiety and
      spasmolytics. We observed the extract of Melissa officinalis L. (MOE) on cell
      proliferation and neuroblast differentiation in the hippocampal dentate gyrus
      (DG) of middle-aged mice (12 months of age) using Ki67 and doublecortin (DCX),
      respectively. We also observed changes in corticosterone, GAD67 and GABA
      transaminase (GABA-T) to check their possible mechanisms related to neurogenesis.
      We administered 50 or 200 mg/kg MOE to the animals once a day for 3 weeks. For
      labeling of newly generated cells, we also administered 5-bromodeoxyuridine
      (BrdU) twice a day for 3 days from the day of the first MOE treatment.
      Administration of 50 or 200 mg/kg MOE dose-dependently increased Ki67 positive
      nuclei to 244.1 and 763.9% of the vehicle-treated group, respectively. In
      addition, 50 or 200 mg/kg MOE significantly increased DCX positive neuroblasts
      with well-developed (tertiary) dendrites. Furthermore, MOE administration
      significantly increased BrdU/calbindin D-28 k double labeled cells (integrated
      neurons into granule cells in the DG) to 245.2% of the vehicle-treated group. On
      the other hand, administration of MOE reduced corticosterone levels in serum and
      decreased GABA-T levels in the DG homogenates. These results suggest that MOE
      increases cell proliferation, neuroblast differentiation and integration into
      granule cells by decreasing serum corticosterone levels as well as by increasing
      GABA levels in the mouse DG.

PMID- 21076870
TI  - Chlorpyrifos induced region specific vulnerability in rat CNS and modulation by
      age and cold stress: an interactive study.
AB  - Chlorpyrifos (CPF), an organophosphorus insecticide is known to cause ill health
      in non-target animals by inducing oxidative stress. In this study influence of
      cold stress (15 degrees C and 20 degrees C) and age as modulating factors on CPF
      induced oxidative stress was addressed to assess age-related differences and
      vulnerability in central nervous system of rats. The results indicated an
      interaction with age and cold exposure resulting in marked decreased activity
      levels of SOD (P < 0.05), CAT (P < 0.05), GPx (P < 0.05), GST (P < 0.05) followed
      by increased MDA (P < 0.05) and decreased GSH levels (P < 0.05). The ANOVA and
      Post-hoc analysis showed that antioxidant enzymes decreased significantly (P <
      0.05) on CPF exposure. Moreover synergistic action of CPF and cold stress at 15
      degrees C caused higher inhibition on comparison with CPF and cold stress alone
      and together at 20 degrees C indicating the extent of peroxidative damage in
      discrete regions of CNS. Further this study showed young individuals to be more
      sensitive than adults.

PMID- 21076872
TI  - Destructive weighted Poisson cure rate models.
AB  - In this paper, we develop a flexible cure rate survival model by assuming the
      number of competing causes of the event of interest to follow a compound weighted
      Poisson distribution. This model is more flexible in terms of dispersion than the
      promotion time cure model. Moreover, it gives an interesting and realistic
      interpretation of the biological mechanism of the occurrence of event of interest
      as it includes a destructive process of the initial risk factors in a competitive
      scenario. In other words, what is recorded is only from the undamaged portion of
      the original number of risk factors.

PMID- 21076871
TI  - In search of a solution to the sphinx-like riddle of GM1.
AB  - Among the many glycoconjugates contributing to the sugar code, gangliosides have
      drawn special attention owing to their predominance as the major
      sialoglycoconjugate category within the nervous system. However, their
      occurrence, albeit at lower levels, appears ubiquitous in vertebrate cells and
      even some invertebrate tissues. Now that over 100 gangliosides have been
      structurally characterized, their diverse physiological functions constitute a
      remaining enigma. This has been especially true of GM1, for which a surprising
      array of functions has already been revealed. Our current research has focused on
      two areas of GM1 function: (a) signaling induced in neural and immune cells by
      cross-linking of GM1 in the plasma membrane that leads to activation of TRPC5
      (transient receptor potiential, canonical form 5) channels, a process important
      in neuritogenesis and autoimmune suppression; (b) activation by GM1 of a sodium
      calcium exchanger (NCX) in the inner membrane of the nuclear envelope (NE) with
      resulting modulation of nuclear and cellular calcium. The latter has a role in
      maintaining neuronal viability, loss of which renders neurons vulnerable to
      Ca(2+) overload. Pathological manifestations in mutant mice and their cultured
      neurons lacking GM1 have shown dramatic rescue with a membrane permeable
      derivative of GM1 that enters the nucleus and restores NCX activity. Nuclear
      function of GM1 is related to the presence of neuraminidase in the NE, an enzyme
      that generates GM1 through hydrolysis of GD1a. A different isoform of this enzyme
      was found in each of the two membranes of the NE.

PMID- 21076873
TI  - Quantitative coronary analysis in the Nordic Bifurcation studies.
AB  - Quantitative coronary analysis (QCA) of bifurcation lesions in the Nordic
      Bifurcation studies was performed using software dedicated to bifurcating
      vessels. By now, pre-PCI, post-PCI and 8-month follow-up angiograms of 957
      patients have been analyzed in the first three Nordic Bifurcation studies. Large
      scale clinical studies with specific areas of interest require QCA software with
      high intra- and inter observer reproducibility, an efficient workflow, flexible
      features of analysis, a detailed output, and facilities for data export.
      Recently, a dedicated second generation 2D QCA bifurcation software became
      commercially available. We used this new software in the third Nordic Bifurcation
      study for efficient and tailored analysis. Despite widespread automation of the
      analysis process and experienced observers, an elaborate standard operating
      procedure is still essential for standardized high quality QCA analysis of
      bifurcation lesions.

PMID- 21076874
TI  - Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk
      of head and neck cancer.
AB  - Many studies have investigated the association between the CYP2E1 5'-flanking
      region (RsaI/PstI) polymorphism and head and neck cancer susceptibility, but the
      results were conflicting. In this meta-analysis, we assessed 24 published studies
      involving 12,562 subjects of the association between CYP2E1 RsaI/PstI
      polymorphism and head and neck cancer risk. Using the fixed effects model, we
      found significant association between PstI/RsaI polymorphism and head and neck
      cancer risk [OR=1.11 (95%CI: 1.00-1.22) for c2 allele (P=0.04) and OR=1.57 (95%
      CI: 1.14-2.15) for c2 homozygous (P=0.006) compared with wild type homozygote].
      Significant results were also found in East Asians and Mix populations when
      stratified by ethnicity. However, no significant associations were found for
      Caucasians in all genetic models. Stratified analyses according to source of
      controls, significant associations were found only in hospital base controls. In
      the subgroup analyses by tumor types, significant association was detected only
      in oral cancer group, while no significant associations among laryngeal- or
      pharyngeal- cancer subgroup. This meta-analysis suggests that the CYP2E1
      RsaI/PstI polymorphism may be a risk factor for head and neck cancer in Asians
      and Mix population, and that different carcinogenic processes involved in the
      genesis of various tumor types may exist.

PMID- 21076875
TI  - Genetic polymorphism analysis of 15 STR loci in Chinese Hui ethnic group residing
      in Qinghai province of China.
AB  - In the present study, we investigated the diversity distributions of allelic
      frequencies of 15 short tandem repeats (STRs) loci in a sample of Chinese Hui
      ethnic group in the Ningxia Hui Autonomous Region. The allelic frequencies of the
      15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539,
      D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were obtained from 2975
      unrelated healthy Hui individuals. The STR genotyping data of all the samples
      were generated by DNA extraction, multiple amplification, GeneScan and genotype
      analysis. The genetic distances among different populations were calculated by
      using Nei's method and a phylogenetic tree was constructed based on the allelic
      frequencies of the same 15 STR loci using the neighbor-joining method. A total of
      185 alleles were observed in the Hui population, with the corresponding allelic
      frequencies ranging from 0.0002 to 0.5322. Chi-Square tests showed that all STR
      loci were in Hardy-Weinberg equilibrium. The forensic statistical parameters of
      all the loci showed high values. The population data in this study were compared
      with the previously published population data from other ethnics or areas. The
      Hui population showed significant differences from the Minnan Han, Uigur, Ewenki,
      Yi, Tibetan, Maonan and Malay ethnic minority groups in some loci, and from the
      South Morocco population and the Moroccan population in all the loci. Our results
      are valuable for human individual identification and paternity testing in the
      Chinese Hui population and are expected to enrich the genetic information
      resources of Chinese populations.

PMID- 21076876
TI  - The significance of lifeworld and the case of hospice.
AB  - Questions on what it means to live and die well are raised and discussed in the
      hospice movement. A phenomenological lifeworld perspective may help professionals
      to be aware of meaningful and important dimensions in the lives of persons close
      to death. Lifeworld is not an abstract philosophical term, but rather the
      opposite. Lifeworld is about everyday, common life in all its aspects. In the
      writings of Cicely Saunders, known as the founder of the modern hospice movement,
      facets of lifeworld are presented as important elements in caring for dying
      patients. Palliative care and palliative medicine today are, in many ways,
      replacing hospices. This represents not only a change in name, but also in the
      main focus. Hospice care was originally very much about providing support and
      comfort for, and interactions with the patients. Improved medical knowledge today
      means improved symptomatic palliation, but also time and resources spent in other
      ways than before. Observations from a Nordic hospice ward indicate that seriously
      ill and dying persons spend much time on their own. Different aspects of
      lifeworld and intersubjectivity in the dying persons' room is presented and
      discussed.

PMID- 21076877
TI  - Design and management of an orthopaedic bone bank in The Netherlands.
AB  - The design and management of an orthopaedic bone bank is a complex process in
      which medical organisation and legislation intertwine. Neither in the
      Netherlands, nor in any other European country, there are official guidelines for
      the organisation and management of an orthopaedic bone bank. In the Netherlands,
      the recently modified 'law of security and quality for using human materials'
      (WVKL) dictates requirements for technical and organisational aspects for the use
      of human tissue and cells. The bone bank procedures include a thorough
      questionnaire for donor selection, extensive serological, bacteriological and
      histopathological examination, as well as standard procedures for registration,
      processing, preservation, storage and distribution of bone allografts. This
      article describes the organisation of an accredited bone bank and can be used as
      a proposition for an official guideline or can be useful as an example for other
      orthopaedic bone banks in Europe.

PMID- 21076878
TI  - The efficacy of botulinum toxin type A in managing chronic musculoskeletal pain:
      a systematic review and meta analysis.
AB  - BACKGROUND: Botulinum toxin type A (BoNTA) is a neurotoxin that acts by
      inhibiting the release of neurotransmitters acetylcholine at neuromuscular
      junctions, thus reducing muscular contractions. Recent evidence suggests that
      BoNTA can reduce nociceptive activities of sensory neurons in animal models by
      inhibiting release of certain neuropeptides. Despite the therapeutic benefit of
      BoNTA in alleviating painful muscle spasms, its efficacy in other musculoskeletal
      pain conditions is less clear. OBJECTIVE: We aim to examine the efficacy of BoNTA
      in reducing chronic musculoskeletal pain. METHODS: Studies for inclusion in our
      report were identified using MEDLINE, EMBASE, PUBMED, Cochrane Central Register
      of Controlled Trials, CINAHL, and reference lists of relevant articles. Studies
      were considered eligible for inclusion if they were randomized controlled trials
      (RCTs), evaluating the efficacy of BoNTA injections in pain reduction. All
      studies were assessed and data were abstracted independently by paired reviewers.
      The outcome measures were baseline and final pain scores as assessed by the
      patients. The internal validity of trials was assessed with the Jadad scale.
      Disagreements were resolved through discussions. MAIN RESULTS: Twenty-one studies
      were included in the systematic review and 15 of them were included in the final
      meta-analysis. There was a total of 706 patients in the meta-analysis,
      represented from trials of plantar fasciitis (n = 1), tennis elbow (n = 2),
      shoulder pain (n = 1), whiplash (n = 3), and myofascial pain (n = 8). Overall,
      there was a small to moderate pain reduction among BoNTA patients when compared
      to control (SMD = -0.27, 95% CI: -0.44 to -0.11). When the results were analyzed
      in subgroups, only tennis elbow (SMD = -0.44, 95% CI: -0.86 to -0.01) and plantar
      fasciitis (SMD = -1.04, 95% CI: -1.68 to -0.40) demonstrated significant pain
      relief. Although not in the meta-analysis, one back pain study also demonstrated
      positive results for BoNTA. Lastly, BoNTA was effective when used at >= 25 units
      per anatomical site or after a period >= 5 weeks. CONCLUSION: In our meta
      analysis, BoNTA had a small to moderate analgesic effect in chronic
      musculoskeletal pain conditions. It was particularly effective in plantar
      fasciitis, tennis elbow, and back pain, but not in whiplash or shoulder pain
      patients. However, more evidence is required before definitive conclusions can be
      drawn. On the other hand, there is convincing evidence that BoNTA lacks strong
      analgesic effects in patients with myofascial pain syndrome. A general dose
      dependent and temporal response with BoNTA injections was also observed.

PMID- 21076880
TI  - A glycerol alpha-D-glucuronide and a megastigmane glycoside from the leaves of
      Guettarda speciosa L.
AB  - From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Guettarda
      speciosa L., two new compounds (1, 2) were isolated together with six known
      compounds. Spectroscopic analysis of 1 and 2 established their structures to be
      derivatives of a glycerol alpha-glucuronide and a megastigmane glycoside,
      respectively. HPLC analysis of the hydrolyzate of 1 confirmed the presence of D
      glucuronic acid in the structure, and the modified Mosher's method established
      the absolute structure of 2.

PMID- 21076881
TI  - Rapid determination of atropine and scopolamine content in scopolia extract
      powder by HPLC.
AB  - A rapid method that does not require a complicated preparation was developed for
      determining by HPLC the content of atropine (At) and scopolamine (Sc) in a sample
      of scopolia extract powder. The sample solution for HPLC was extracted using 0.1
      mol/L HCl/methanol (8:2). At and Sc were separated using a
      pentafluorophenylpropyl column and detected at a wavelength of 210 nm.
      Acetonitrile-10 mmol/L ammonium acetate adjusted to pH 5.0 (8:2, v/v) was used as
      the mobile phase. The linearity was good in the 5.0-500 MUg/mL range for At and
      0.5-500 MUg/mL range for Sc. The specificity for both At and Sc was satisfactory.
      The quantitation limits were 5.0 MUg/mL for At and 0.5 MUg/mL for Sc. The
      quantitative values of total alkaloid calculated using this method were higher
      (1.3-3.7%) than those obtained using the Japanese Pharmacopoeia Fifteenth Edition
      (JP15) method. The precision of this method, measured as the standard deviation,
      was found to be satisfactory and comparable to that of the JP15 method,
      determined by an analysis of 3 commercial scopolia extract powder samples.

PMID- 21076879
TI  - Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized
      older patients.
AB  - The association between angiotensin-converting enzyme (ACE) genotypes and
      functional decline in older adults remains controversial. To assess if ACE gene
      variations influences functional abilities at older age, the present study
      explored the association between the common ACE insertion/deletion (I/D)
      polymorphism and disability measured with activities of daily living (ADL) in
      hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I,
      I/D, and D/D) in a population of 2,128 hospitalized older patients divided
      according to presence or absence of ADL disability. Logistic regression analysis
      adjusted for possible confounding factors, identified an association between the
      I/I genotype with ADL disability (OR=1.54, 95% CI 1.04-2.29). This association
      was significant in men (OR=2.01, 95% CI 1.07-3.78), but not in women (OR=1.36,
      95% CI 0.82-2.25). These results suggested a possible role of the ACE
      polymorphism as a genetic marker for ADL disability in hospitalized older
      patients.

PMID- 21076882
TI  - Flavonol glycosides from the leaves of Indigofera zollingeriana.
AB  - Two new flavonol glycosides were isolated from the 1-butanol (1-BuOH)-soluble
      fraction of a methanol (MeOH) extract of the leaves of Indigofera zollingeriana,
      along with four flavonol glycosides and three known megastigmane glucosides. The
      structures of the new compounds were elucidated by spectroscopic analyses as
      kaempferol 3-O-beta-D-(2"-O-beta-D-apiofuranosyl)glucopyranoside 7-O-alpha-L
      rhamnopyranoside and 3-O-beta-D-(2"-O-beta-D-apiofuranosyl, 6"-O-alpha-L
      rhamnopyranosyl)glucopyranoside 7-O-alpha-L-rhamnopyranoside.

PMID- 21076883
TI  - Beneficial effect of Sparassis crispa on stroke through activation of Akt/eNOS
      pathway in brain of SHRSP.
AB  - Sparassis crispa (S. crispa) is a mushroom used as a natural medicine that
      recently became cultivatable in Japan. In this study, we investigated not only
      the preventive effects of S. crispa against stroke and hypertension in stroke
      prone spontaneously hypertensive rats (SHRSP) but also the mechanism involved by
      using studies of the cerebral cortex at a young age. Six-week-old male SHRSP were
      divided into 2 groups, a control group and an S. crispa group administered 1.5%
      S. crispa in feed, and we then observed their survival. In addition, rats of the
      same age were treated with 1.5% S. crispa for 4 weeks and we measured body
      weight, blood pressure, blood flow from the tail, NO(x) production, and the
      levels of expression of several proteins in the cerebral cortex by western blot
      analysis. Our results showed that the S. crispa group had a delayed incidence of
      stroke and death and significantly decreased blood pressure and increased blood
      flow after the administration. Moreover, the quantity of urinary excretion and
      the nitrate/nitrite concentration in cerebral tissue were higher than those of
      control SHRSP rats. In the cerebral cortex, phosphor-eNOS (Ser1177) and phosphor
      Akt (Ser473) in S. crispa-treated SHRSP were increased compared with those of
      control SHRSP rats. In conclusion, S. crispa could ameliorate cerebrovascular
      endothelial dysfunction by promoting recovery of Akt-dependent eNOS
      phosphorylation and increasing NO production in the cerebral cortex. S. crispa
      may be useful for preventing stroke and hypertension.

PMID- 21076884
TI  - Diffusion-weighted magnetic resonance imaging in focal breast lesions: analysis
      of 78 cases with pathological correlation.
AB  - PURPOSE: This study assessed the usefulness of magnetic resonance diffusion
      weighted imaging (DWI) in distinguishing between benign and malignant breast
      lesions. MATERIALS AND METHODS: Gadolinium-enhanced magnetic resonance imaging
      (MRI) and DWI with determination of the apparent diffusion coefficient (ADC) were
      performed on 78 women, each with a focal breast lesion at least 7 mm in diameter,
      which was studied by cytology or histology. RESULTS: Final diagnoses were
      obtained by cytology in 29 cases and histology in 49 (11 percutaneous biopsies
      and 38 surgical specimens). There were 43 benign lesions (13 fibrocystic disease,
      eight fibroadenoma, seven adenosis, five normal breast tissue, four inflammatory
      lesions, three intramammary lymph nodes, two scleroelastosis and one fat
      necrosis) and 35 malignant lesions (30 invasive ductal carcinoma, two invasive
      lobular carcinoma, one ductal carcinoma in situ, one carcinomatous mastitis and
      one metastasis from neuroendocrine carcinoma). The mean ADC values were 1.677+/
      0.151 for benign lesions and 1.298+/-0.129 for malignant lesions (p<0.001). With
      an ADC cutoff value of 1.48, DWI had 88.6% sensitivity [confidence interval (CI)
      78.1%-99.1%] and 95.3% specificity (CI 88.9%-100%), with 31 true positives, four
      false negatives (three invasive ductal carcinoma and one carcinomatous mastitis),
      41 true negatives and two false positives (one fat necrosis and one
      fibroadenoma). With the cutoff value set at 1.52, DWI sensitivity (35 true
      positive, no false negative) was 100% and specificity was 86% (CI 75.7%-96.3%)
      due to 37 true negatives and six false positives (an additional two fibroadenoma
      and two fibrocystic disease compared with those recorded with the cutoff set at
      1.48). The overall accuracy of DWI considering both cutoff values (72 correct
      evaluations out of 78 cases) was 92.3% (CI 86.4%-98.2%). CONCLUSIONS: DWI is a
      reliable tool for characterising focal breast lesions.

PMID- 21076885
TI  - Evaluation of coronary artery in-stent restenosis with prospectively ECG
      triggered axial CT angiography versus retrospective technique: a phantom study.
AB  - PURPOSE: This study compared the performance of prospectively
      electrocardiographically (ECG)-triggered axial computed tomography (CT)
      angiography with retrospective technique in evaluating coronary artery stent
      restenosis by 64-slice CT. MATERIALS AND METHODS: A pulsing cardiac phantom with
      artificial coronary artery in-stent restenosis was examined by CT angiography
      with different types of scan modes. The visibility of in-stent restenosis was
      evaluated with a three-point score. Artificial lumen narrowing [(inner stent
      diameter-measured lumen diameter)/inner stent diameter], lumen attenuation
      increase ratio [(in-stent attenuation-coronary artery lumen attenuation)/coronary
      artery lumen attenuation], measurement error of restenosis percent [(known
      restenosis percent-measured restenosis percent)/known restenosis percent] and
      imaging noise were analysed. RESULTS: Prospective acquisition showed better
      visibility than retrospective acquisition (p<0.05): 61% of in-stent restenoses
      had good visibility on the prospective acquisition compared with 17% on the
      retrospective acquisition. Furthermore, the effective dose was 6.2 +/- 0.3 mSv
      for the prospective technique compared with 18.8 +/- 1.1 mSv for the
      retrospective technique. Artificial lumen narrowing (mean 40%), lumen attenuation
      increase ratio (mean 33%) and measurement error of restenosis percent were not
      different between types of CT acquisitions. CONCLUSIONS: Compared with the
      traditional retrospective technique, prospective coronary CT angiography offers
      improved image quality and reduces effective radiation dose in evaluating in
      stent restenosis.

PMID- 21076886
TI  - Coaxial biopsy during percutaneous vertebroplasty in patients with presumed
      osteoporotic vertebral compression fractures: retrospective review of biopsy
      results.
AB  - PURPOSE: This study retrospectively analysed the results of biopsies obtained
      during percutaneous vertebroplasty (PVP) in patients with presumed osteoporotic
      vertebral compression fractures, with a view to highlighting the importance of
      coaxial biopsy in determining the aetiology of vertebral fractures and planning
      subsequent treatment. MATERIALS AND METHODS: Between November 2003 and March
      2009, 98 patients (78 women; 20 men) with a clinical and imaging suspicion of
      osteoporotic vertebral compression fractures underwent coaxial biopsy in
      conjunction with PVP of the thoracic and lumbar vertebrae. Mean age at the time
      of the procedure was 72.6 years. A pathologist interpreted all the biopsy
      samples. RESULTS: In 83 patients, the biopsy results were consistent with the
      presumed osteoporotic aetiology. In two patients, a malignancy was identified.
      Biopsy samples from 13 patients were considered insufficient or unsuitable by the
      pathologist for evaluation. CONCLUSIONS: Despite the number of biopsy samples
      considered insufficient or unsuitable, coaxial biopsy during PVP is useful in
      verifying the presumed aetiology of vertebral compression fractures, which is
      often unclear on the basis of clinical and imaging examinations. It is therefore
      both convenient and advisable to perform a vertebral coaxial biopsy in all
      patients undergoing a PVP.

PMID- 21076887
TI  - Novel PKCs activate ERK through PKD1 in MCF-7 cells.
AB  - PKCs can have opposite effects on ERK phosphorylation. Novel (n)PKCs can inhibit
      ERK by phosphorylation of Raf-1, classical and atypical PKCs can activate ERK by
      removing an inhibitory protein from Raf-1. The aim of this work was to clarify
      how PMA-activated PKCs lead to ERK activation in MCF-7 cells expressing mainly
      nPKCs. Using chemical inhibitors and antibodies against PKCs, delivered into
      cells by the Chariot transfection system, we found that nPKCs activate ERK
      through transphosphorylation of PKD1, the blockage of which prevented PMA
      stimulated ERK activation. We conclude that the nPKCs/PKD1 cascade is determinant
      for ERK activation by PMA in MCF-7 cells.

PMID- 21076888
TI  - The utility of 99mTc-sestamibi scintigraphy in the localisation of parathyroid
      adenomas in primary hyperparathyroidism.
AB  - BACKGROUND: There are conflicting data in the literature about the sensitivity of
      sestamibi scintigraphy in parathyroid tumour localisation in primary
      hyperparathyroidism (PHPT). AIM: We aimed to evaluate the overall sensitivity of
      this modality in parathyroid tumour localisation and to determine clinical and
      biochemical factors which influence sensitivity of this method. METHODS: We
      performed a retrospective review of 57 patients with a biochemical diagnosis of
      PHPT who had sestamibi scintigraphy performed. RESULTS: The sensitivity of
      sestamibi scanning was 56% in whole group and 63% in those without nodular
      thyroid disease. Among the patients with confirmed single gland disease
      (biochemical cure after surgical removal of a single adenoma), sensitivity was
      71%. A positive scan was associated with younger age, greater adenoma weight and
      higher pre-operative serum calcium. Concordance between the sestamibi and neck
      ultrasonography was 92% accurate in pre-operative tumour localisation.
      CONCLUSION: Sestamibi scintigraphy was more likely to be positive in younger
      patients without nodular thyroid disease who have larger parathyroid adenomas
      with more severe hyperparathyroidism.

PMID- 21076889
TI  - Bilateral pneumothorax in pregnancy unmasking lymphangioleiomyomatosis.

PMID- 21076890
TI  - Protective effect of FK506 on myocardial ischemia/reperfusion injury by
      suppression of CaN and ASK1 signaling circuitry.
AB  - We investigated protective effect of FK506 on rat hearts subjected to
      ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were
      divided into four groups: Ischemia/reperfusion group (I/R), FK506 +
      Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506
      sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30
      min and subsequently reperfusing for 120 min. FK506 was administered 15 min
      before ischemia. Rats in sham group and FK506-sham group were operated only by
      placing a ligature around the coronary artery, and the blood supply was not
      blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks
      of histopathological changes in damaged cardiac tissues. FK506 reduced the
      infarct size and inhibited the activation of CaN enzyme in FK506-I/R group.
      Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected
      myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein
      level decreased significantly after I/R injury in FK506-treated I/R heart. FK506
      suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway,
      and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling
      circuitry are involved in protective effect of FK506 on rat myocardium I/R
      injury.

PMID- 21076891
TI  - Homocysteine induces oxidative-nitrative stress in heart of rats: prevention by
      folic acid.
AB  - Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and
      thrombosis; however, the mechanisms by which homocysteine triggers these
      dysfunctions are not fully understood. In the present study, we investigated the
      effect of chronic hyperhomocysteinemia on some parameters of oxidative stress,
      namely thiobarbituric acid reactive substances, an index of lipid peroxidation,
      2',7'-dichlorofluorescein (H(2)DCF) oxidation, activities of antioxidant enzymes
      named superoxide dismutase and catalase, as well as nitrite levels in heart of
      young rats. We also evaluated the effect of folic acid on biochemical alterations
      elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous
      injection of homocysteine (0.3-0.6 MUmol/g body weight) and/or folic acid (0.011
      MUmol/g body weight) from their 6th to the 28th day of life. Controls and treated
      rats were killed 1 h and/or 12 h after the last injection. Results showed that
      chronic homocysteine administration increases lipid peroxidation and reactive
      species production and decreases enzymatic antioxidant defenses and nitrite
      levels in the heart of young rats killed 1 h, but not 12 h after the last
      injection of homocysteine. Folic acid concurrent administration prevented
      homocysteine effects probable by its antioxidant properties. Our data indicate
      that oxidative stress is elicited by chronic hyperhomocystenemia, a mechanism
      that may contribute, at least in part, to the cardiovascular alterations
      characteristic of hyperhomocysteinemic patients. If confirmed in human beings,
      our results could propose that the supplementation of folic acid can be used as
      an adjuvant therapy in cardiovascular alterations caused by homocysteine.

PMID- 21076892
TI  - Subarachnoid hemorrhage: the first 24 hours. A surgeon's perspective.
AB  - BACKGROUND: The first 24 h in the management of aneurysmal subarachnoid
      hemorrhage (SAH) represent a critical time period for medical intervention.
      METHODS: We review the current literature and discuss our current clinical
      practices related to management of acute SAH. RESULTS: A brief objective review
      of the current evidence along with a subjective overview of the authors practices
      in the management of aneurysmal subarachnoid hemorrhage in the first 24 h is
      outlined. CONCLUSIONS: The first 24 h following aneurysmal subarachnoid
      hemorrhage is a critical time period in which medical and interventional
      management paradigms continue to evolve.

PMID- 21076893
TI  - Clinical decision making: an introduction.

PMID- 21076894
TI  - Meta-analysis to estimate the correlation coefficients between birthweight and
      other anthropometric measurements at birth.
AB  - OBJECTIVE: To pool the correlation coefficients between birthweight (BW) and
      other newborn anthropometric measurements at birth. METHODS: Meta-analysis, using
      a random-effects model. Any study, published in the English language, showing the
      correlation coefficients between BW and other anthropometric measurements of
      living neonates at birth was eligible. The Z- scores, transformed from the
      correlation coefficients were pooled, and afterwards they were back transformed
      to the pooled correlation coefficients. RESULTS: The correlations of BW with (mid
      upper-) arm circumference (MUAC) and chest circumference (CHC) were frequently
      studied (n, 76 and 71; pooled correlation coefficient, 0.81 and 0.84; 95%CI, 0.78
      0.84 and 0.82-0.86). The Z- scores of the pooled correlation coefficient between
      BW vs. CHC, the highest among the correlation coefficients of BW, was not
      substantially different from the Z- scores between BW vs. calf circumference
      (CC), thigh circumference (TC), MUAC, or abdominal circumference (AC) (p, 0.889,
      0.351, 0.076, and 0.053, respectively), but the study numbers of CC, TC, or AC
      were remarkably low (n, 13, 19, and 6, respectively) compared with CHC or MUAC.
      CONCLUSIONS: CHC and MUAC may be among the most promising candidates as the
      surrogates of BW, based on the study numbers, and the level of pooled correlation
      coefficients.

PMID- 21076895
TI  - Cardiovascular disease in chronic kidney disease: data from the Kidney Early
      Evaluation Program (KEEP).
AB  - Diabetes mellitus (DM) and hypertension (HTN) are leading joint risk factors for
      both cardiovascular disease (CVD) and chronic kidney disease (CKD). In the
      nationwide KEEP (Kidney Early Evaluation Program) an estimated glomerular
      filtration rate less than 60 mL/min/1.73 m(2) or a urine albumin:creatinine ratio
      >=30 mg/g (3.4 mg/mmol) defines CKD. Overall in KEEP, the rates of identified CKD
      and self-reported CVD are 25.7% and 22.1%, respectively. The presence of CKD has
      been associated with younger ages of self-reported myocardial infarction and
      stroke. The combination of CVD and CKD in KEEP has been associated with shorter
      survival time. Finally, the presence of CVD or a prior history of coronary
      revascularization has been associated with modestly better rates of CVD risk
      factor control; however, the majority of patients with CKD have suboptimally
      controlled blood pressure, glucose, or lipids. These data suggest that patients
      with CKD are not only at higher risk for CVD and subsequent mortality, but are
      also ideal for targeted community--and practice-based interventions to improve
      risk factor control and, hopefully, reduce rates of subsequent cardiovacular
      events.

PMID- 21076896
TI  - Hip dislocation: are hip precautions necessary in anterior approaches?
AB  - BACKGROUND: In 2005, we reported removal of functional restriction after primary
      THA performed through the anterolateral approach did not increase the incidence
      of dislocation. QUESTIONS/PURPOSES: To develop a current practice guideline, we
      evaluated the incidence of early dislocation after primary THA after
      implementation of a no-restriction protocol. METHODS: Between January 2005 and
      December 2007, 2532 patients (2764 hips; 1541 women, 1223 men; mean age, 63.2
      years [28-98 years]) underwent primary THA at our institution. Bilateral THA was
      performed in 232 patients (464 hips). The direct anterior or anterolateral
      approach was used in all patients. Femoral head size was 28, 32, or 36 mm.
      Patients were given no traditional functional restrictions postoperatively, such
      as use of elevated seats, abduction pillows, and restriction from driving. All
      patients received standard care at the judgment of the attending surgeon. One
      hundred forty-six patients missed followup appointments despite efforts to be
      contacted by telephone. The remaining 2386 of 2532 patients (94%) had a minimum
      followup of 6 months (mean, 14.2 months; range, 6-34 months). RESULTS: Four known
      dislocations occurred in the followed cohort of 2386 patients with 2612 hips
      (0.15%) at a mean of 5 days (3-12 days) postoperatively, none related to high
      impact trauma. One dislocation occurred in a patient with a history of
      developmental dysplasia of the hip, two dislocations occurred while at the toilet
      (one with a previous hip fracture treated with a modular system), and one
      dislocation was idiopathic. CONCLUSIONS: We confirmed a low incidence of
      dislocation after primary THA in the absence of early postoperative restrictions.
      We conclude a no-restriction protocol does not increase the incidence of early
      dislocation after primary THA. LEVEL OF EVIDENCE: Level II, therapeutic study.
      See the Guidelines for Authors for a complete description of levels of evidence.

PMID- 21076897
TI  - No strength or gait benefit of two-incision THA: a brief followup at 1 year.
AB  - BACKGROUND: Using comprehensive gait analysis and strength testing, we previously
      investigated the early (2-month) functional outcome after THA using two-incision
      and mini-posterior surgical approaches and found an advantage for the mini
      posterior approach. Benefits included improved muscle strength, a less antalgic
      gait, and better hip function as reflected by changes in hip moments during level
      walking and stair climbing. We questioned how these differences in function would
      fare with longer followup. QUESTIONS/PURPOSES: We determined whether the observed
      early functional advantages for the mini-posterior technique over the two
      incision technique were still present 1 year postoperatively. PATIENTS AND
      METHODS: We prospectively enrolled 22 patients with primary degenerative
      arthritis of the hip; of these, 21 completed gait and strength testing at 2
      months, and 19 completed comprehensive gait and strength testing at 1 year (11
      two-incision hips, eight mini-posterior hips). The 19 patients included 11 men
      and eight women with a mean age of 65 years (range, 40-85 years) and a mean (BMI)
      of 29 (range, 21-39). RESULTS: At 1 year postoperatively, the patients who had
      the mini-posterior THA had greater improvement in hip flexion strength and
      internal rotation strength, greater increase in hip flexor internal moment, and
      greater increase in single-leg stance time on level ground over the patients who
      had the two-incision THA. CONCLUSIONS: Compared with the two-incision approach,
      patients undergoing mini-posterior THA had persistently better function,
      including hip flexor and internal rotator muscle strength, hip flexor internal
      moment, and single-leg stance during level walking. LEVEL OF EVIDENCE: Level II,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21076898
TI  - Comparison of long-term mortality risk following normal exercise vs adenosine
      myocardial perfusion SPECT.
AB  - BACKGROUND: A higher frequency of clinical events has been observed in patients
      undergoing pharmacological vs exercise myocardial perfusion single-photon
      emission computed tomography (SPECT). While this difference is attributed to
      greater age and co-morbidities, it is not known whether these tests also differ
      in prognostic ability among patients with similar clinical profiles. METHODS AND
      RESULTS: We assessed all-cause mortality rates in 6,069 patients, followed for
      10.2 +/- 1.7 years after undergoing exercise or adenosine SPECT. We employed
      propensity analysis to match exercise and adenosine subgroups by age, gender,
      symptoms, and coronary risk factors. Within our propensity-matched cohorts,
      adenosine patients had an annualized mortality rate event rates that was more
      than twice that of exercise patients (3.9% vs 1.6%, P < .0001). Differences in
      mortality persisted among age groups, including those <55 years old. In the
      exercise cohort, mortality was inversely related to exercise duration, with
      comparable mortality noted for patients exercising <3 min and those undergoing
      adenosine testing. CONCLUSIONS: Among patients with normal stress SPECT tests,
      those undergoing adenosine testing manifest a mortality rate that is
      substantially higher than that observed among adequately exercising patients, but
      comparable to that observed among very poorly exercising patients. This elevated
      risk underscores an important challenge for managing patients undergoing
      pharmacological stress testing.

PMID- 21076899
TI  - Myocardial perfusion scintigraphy before and after cardioversion for atrial
      fibrillation: recovery of quantitative parameters.

PMID- 21076900
TI  - Correlates of continued tobacco use and intention to quit smoking among Russian
      cancer patients.
AB  - BACKGROUND: Tobacco use among cancer patients is associated with adverse health
      outcomes. Little attention has been paid to tobacco use among cancer patients in
      developing countries, including Russia, where tobacco use is extremely high, and
      there is little public health infrastructure to address this issue. PURPOSE: This
      study examined medical, socio-demographic, and psychological correlates of
      smoking status and intention to quit smoking among newly diagnosed Russian cancer
      patients. METHOD: A cross-sectional study was conducted with 294 current or
      former smokers newly diagnosed with cancer. RESULTS: Compared with patients who
      quit smoking, patients who continued to smoke were more likely to report urges to
      smoke to satisfy positive reinforcing aspects of tobacco use. Compared with
      patients who were smoking and reported no intention to quit smoking in the next 3
      months, patients who were smoking but intended to quit smoking reported higher
      levels of perceived risks associated with continued smoking and higher levels of
      self-efficacy to quit smoking. CONCLUSION: As commitment to developing smoking
      cessation treatment programs for cancer patients in Russia emerges, these data
      can help guide the development of behavioral interventions to assist patients
      with quitting smoking, enhancing their chances for improved clinical outcomes.

PMID- 21076903
TI  - [Renaissance of the Classical World : back to the roots in multiple sclerosis
      imaging].

PMID- 21076901
TI  - Protective effect of curcumin and its combination with piperine (bioavailability
      enhancer) against haloperidol-associated neurotoxicity: cellular and
      neurochemical evidence.
AB  - Long-term treatment with haloperidol is associated with a number of
      extrapyramidal side effects, particularly the irregular movements of chorionic
      type. This limitation presents a marked therapeutic challenge. The present study
      investigates the molecular etiology of haloperidol neurotoxicity and the role of
      curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The
      redox status of haloperidol-treated brains along with NO, TNF-alpha, NF-kappaB
      p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the
      striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21
      days) produced orofacial dyskinetic movements which were coupled with marked
      increase in oxidative stress parameters, TNF-alpha, caspase-3 activity in
      cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the
      striatum. Neurochemically, chronic administration of haloperidol resulted in a
      significant decrease in the levels of norepinephrine, dopamine, and serotonin.
      The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days)
      produced mild oxidative stress but did not alter any other parameters.
      Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days)
      dose-dependently prevented all the behavioral, cellular, and neurochemical
      changes associated with the chronic administration of haloperidol. Curcumin per
      se (50 mg/kg) did not show any side effects. Co-administration of piperine
      significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50
      mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct
      to haloperidol treatment and provided initial clues to the underlying molecular
      mechanisms in haloperidol neurotoxicity. This study also provides a rationale for
      the combination of piperine and curcumin.

PMID- 21076902
TI  - Hyperparathyroidism, an emerging disease.
AB  - A retrospective study based on 35 years of personal experience was done. Up to
      today 2,175 patients were operated, 1,318 for primary hyperparathyroidism (HPT)
      and 857 for secondary and tertiary HPT. Considering recent years (1999 to July
      2010), 918 patients were operated for primary HPT. Preoperatively all the
      patients performed a cervical ultrasound and/or a sestamibi scan. Open
      mininvasive procedure was preferred: it is an easily reproducible and costless
      technique. Using magnifying glasses up to 2.5, an excellent three-dimensional
      vision was obtained. The operating time is short and if there are any doubts it
      is possible to extend the exploration to the other side of the neck. Immediate
      and long-term results were excellent, with a cure rate greater than 99%.
      Complications in the treatment of a single adenoma are around 0.3%. Patients can
      be discharged 24-48 h after the operation. Regarding reoperations, a correct
      diagnostic and therapeutic approach is essential. CT, MRI and SPECT must
      correlate with the information given by ultrasound and scintigraphy. The
      intraoperative PTH assay (io-PTH) is required and the approach should be limited
      to the area where the missed gland probably is. The functionality of the
      autotransplantation (AT) performed immediately was good. The functionality of the
      cryopreserved tissue is better for the HPT I in comparison with HPT II.
      Considering HPT I or HPT II the use of io-PTH is helpful. MIBI scanning is
      helpful but not essential, except in reoperations. Surgeon experience is another
      very important factor for good results.

PMID- 21076904
TI  - [Radiation hygiene in medical X-ray imaging. Part 3: radiation exposure of
      patients and risk assessment].
AB  - The frequency of X-ray examinations in Germany and the resulting radiation
      exposure is amongst the highest in comparison with other European countries. To
      reduce medical radiation exposure and to safeguard radiation protection
      regulations, the X-ray ordinance stipulates a justification of each individual X
      ray application. The justification principle means that the X-ray application
      should produce sufficient health benefit to offset the radiation risk. Such a
      benefit-risk assessment needs an adequate estimation of radiation risk. The aim
      of this paper is to explain the principles of benefit-risk assessment for
      different situations (e.g. healthcare and screening). The basics and concepts of
      radiation effects and radiation epidemiology as well as examples of risk
      estimation and benefit-risk assessments are given.

PMID- 21076908
TI  - Enzymes for the biofunctionalization of poly(ethylene terephthalate).
AB  - The functionalization of synthetic polymers such as poly(ethylene terephthalate)
      to improve their hydrophilicity can be achieved biocatalytically using hydrolytic
      enzymes. A number of cutinases, lipases, and esterases active on polyethylene
      terephthalate have been identified and characterized. Enzymes from Fusarium
      solani, Thermomyces insolens, T. lanuginosus, Aspergillus oryzae, Pseudomonas
      mendocina, and Thermobifida fusca have been studied in detail. Thermostable
      biocatalysts hydrolyzing poly(ethylene terephthalate) are promising candidates
      for the further optimization of suitable biofunctionalization processes for
      textile finishing, technical, and biomedical applications.

PMID- 21076909
TI  - [Quality assurance using routine data. Is outcome quality now measurable?].
AB  - Health service quality in Germany can be shown by the data from the external
      quality assurance program (BQS) but as these records are limited to the period of
      in-hospital stay no information about outcome after discharge from hospital can
      be obtained. Secondary routine administrative data contain information about long
      term outcome, such as mortality, subsequent revision and the need for care
      following surgical treatment due to a hip fracture.Experiences in the use of
      secondary data dealing with treatment of hip fractures from the BQS are available
      in our department. In addition we analyzed routine administrative data from the
      health insurance companies Knappschaft Bahn-See and AOK in a cooperative study
      with the WidO (scientific institute of the AOK). These routine data clearly show
      a bias because of poor quality in coding as well as broad interpretation
      possibilities of some of the ICD-10 codes used.Consequently quality assurance
      using routine data is less valid than register-based conclusions. Nevertheless
      medical expertise is necessary to avoid misinterpretation of routine
      administrative data.

PMID- 21076910
TI  - [Intercompartment soft tissue emphysema after arthroscopic meniscus resection.
      Case report and differential diagnosis].
AB  - Soft-tissue emphysema following surgical procedures needs prompt and accurate
      diagnosis in order not to miss severe infections, such as clostridial myonecrosis
      and necrotizing fasciitis. We report the case of a 32-year-old patient who
      developed massive crepitation of the right leg and thoracic wall after knee
      arthroscopy had been performed a few days earlier. He was readmitted under
      suspicion of gas gangrene. This could not be ruled out by preoperative
      examinations as a subacute infection existed in the range of the infrapatellar
      incision. A mini-arthrotomy was carried out to exclude necrotizing soft tissue
      infection and to rinse the joint. An intercompartment emphysema could be
      confirmed intraoperatively. The postoperative course was uneventful. The main
      differential diagnoses of benign soft Tissue emphysema are summarized and
      treatment options are recommended.

PMID- 21076911
TI  - Pathways to psychiatric care in Bangladesh.
AB  - INTRODUCTION: The pattern of care seeking of psychiatric patients is important
      for service and policy issues. We conducted a study in 2008 in Bangladesh to find
      out the referral patterns, delays to reach mental health professional (MHP),
      diagnoses and treatment received before reaching psychiatric care etc. MATERIALS
      AND METHODS: We interviewed 50 consecutive new patients at the Psychiatry
      outpatient department of a tertiary hospital using the translated version of WHO
      pathway encounter form. RESULTS: 84% of the patients we interviewed consulted
      other carers before they arrived at a MHP (2.5-3.1 steps were needed to reach
      MHP) and the range of delay was 8-78 weeks (indirect pathway). 16% of the
      patients came directly to a MHP with mean delay of 10.5 weeks from onset of
      mental illness (direct pathway). Among the patients who took the indirect pathway
      44% first visited the Individual Private practitioners (PP), 22% first visited
      native or religious healers (NRH) and 12% rural medical practitioners (RMP).
      Patients reaching NRH or RMP made the least delay (2-2.5 weeks) and the shortest
      pathway to MHP (4.5-7 weeks). Most delay occurred from PP to MHP/General Hospital
      (22-31 weeks). About a third of patients were informed of diagnosis with poor
      concordance with the diagnosis made by MHP. 70 and 40% of patients with mental
      illness who attended General Hospital and PP were referred to MHP, respectively.
      CONCLUSION: In the study we found four major pathways to mental health care in
      Bangladesh. They are direct pathway and referrals from PP, general hospitals and
      NRH. PP did not play a pivotal role in reaching MHP. Family members had a
      significant role on the decision to seek help from health service.

PMID- 21076912
TI  - Ethnic differences in risk of acute compulsory admission in Amsterdam, 1996-2005.
AB  - PURPOSE: Several European studies have shown that migrants from non-western
      countries are at increased risk of psychotic disorders. This study examines how
      this is reflected in the risk of acute compulsory admission (ACA). METHODS:
      Information on all patients with an ACA in Amsterdam from 1996 to 2005 was linked
      to the Amsterdam municipal register. RESULTS: The incidence of first ACA in
      Amsterdam was 4.5 per 10,000 person years. The incidence risk of ACA for any
      psychiatric disorders and for psychotic disorders in particular showed a 2- to 3
      fold increase in almost all migrant groups from non-western countries, and
      especially for second-generation migrants. In addition, all non-western migrant
      groups were at increased risk of being assessed as posing a danger to others.
      CONCLUSIONS: The relative risk of ACA for psychotic disorders was similar to that
      for the incidence of psychotic disorders in most ethnic groups from other
      studies, suggesting that the increased risk of ACA in non-western migrants can
      mainly be explained by the increased incidence of psychotic disorders in these
      groups. However, the relative risk of ACA for psychotic disorders among Moroccan
      migrants was lower than expected on the basis of incidence studies, which
      suggests that additional factors are relevant, such as illness-related expression
      and access to and quality of care.

PMID- 21076913
TI  - Prevalence of physical, psychological, and sexual abuse among a nationwide sample
      of Arab high school students: association with family characteristics, anxiety,
      depression, self-esteem, and quality of life.
AB  - OBJECTIVES: The objectives were first, to assess the lifetime and 12-month
      prevalence of physical, psychological, and sexual abuse among a stratified random
      sample of Kuwaiti high school students and second, to explore the association of
      child abuse with parental characteristics, subjective quality of life (QOL), self
      esteem, anxiety, and depression. METHOD: We assessed the students for experience
      of abuse by their mothers, fathers, and others, using standard scales on
      psychological, physical and sexual abuse. They also completed the short version
      of the World Health Organization's QOL Instrument; the Rosenberg self-esteem
      scale, and a scale for anxiety and depression. RESULTS: We obtained responses
      from 4,467 students (49% boys), mean age 16.9 years. About 18, 15, and 18%,
      indicated that for at least six times in the past 12 months, they experienced
      psychological abuse by their mothers, fathers and others, respectively. The
      corresponding figures for lifetime experience were similar. The respective
      figures for experience of physical abuse during the past 12 months were 4.3, 5.8,
      and 6.4%. For lifetime experience, the corresponding figures were 3.4, 5.3, and
      5.8%. The girls had significantly higher physical/psychological abuse scores.
      There were no significant gender differences in the prevalence of sexual attacks
      (8.6%) and someone threatening the subjects with sex (5.9%). The prevalence of
      someone sexually exposing themselves to the students (15.3%) and unwanted
      touching of sexual parts (17.4%) was significantly higher among the boys. Over
      one-third of those abused had experienced multiple abuses. Child abuse was
      significantly associated with parental divorce, diminished QOL and self-esteem,
      high scores on anxiety/depression, and difficulty with studies, and social
      relationships. In the regression analysis involving only the abuse indices,
      psychological abuse by mothers was the most important predictor of depression,
      anxiety, and self-esteem (11.5-19.7% of variance). Good quality of parental
      relationship seemed protective. CONCLUSION: The findings support the impression
      that, despite the conservative culture, child abuse is being experienced by a
      significant number of children in the Arab world. Preventive education in this
      culture should include limits on child disciplinary measures, the vulnerable
      groups identified, the impact on psychosocial functioning, and the protective
      effect of parental harmony.

PMID- 21076914
TI  - Suicide and deliberate self-harm in Oxford University students over a 30-year
      period.
AB  - PURPOSE: To determine whether rates of suicide and self-harm in university
      students differ from those in other young people. METHODS: We obtained
      information on Oxford University students who died by suicide or presented to
      hospital following deliberate self-harm (DSH) between 1976 and 2006 from official
      records and a General Hospital monitoring system in Oxford. Rates of suicide and
      self-harm in the students and in other young people in the general population
      were calculated from university, local and national population figures. RESULTS:
      Forty-eight Oxford University students (32 males and 16 females) died by suicide.
      Most (N = 42) were aged 18-25 years. The suicide rate did not differ from that of
      other people in this age group in England and Wales (SMR 105.4; 95% CI 75.2,
      143.4). There was evidence of clustering of methods of suicide over time. During
      the same period, 602 students (383 females and 219 males) presented to the
      General Hospital following DSH. Most (90.7%) were aged 15-24 years, in which age
      group rates of DSH (per 100,000) during term-time were lower than in other young
      people in Oxford City (females: 206.5 vs. 285.6, z = -5.03, p < 0.001; males:
      75.9 vs. 111.2, z = -4.35; p < 0.001). There was an excess of student DSH
      episodes in the main exam term. CONCLUSIONS: Contrary to earlier findings and
      popular belief, suicide rates in Oxford University students do not differ from
      those in other young people. Rates of DSH are significantly lower than in other
      young people. Risk of DSH may increase around the time of examinations.

PMID- 21076915
TI  - RETRACTED ARTICLE: Multimorbidity: not just an older person's issue. Results from
      an Australian biomedical study.

PMID- 21076916
TI  - Electrochemical properties and temperature dependence of a recombinant laccase
      from Thermus thermophilus.
AB  - The electrochemical properties of a laccase from Thermus thermophilus HB27 (Tth
      laccase) were characterized. The gene encoding the laccase was cloned and
      overexpressed in Escherichia coli. One-step purification of the corresponding apo
      enzyme was achieved by nickel-affinity chromatography. Copper was incorporated
      into the apo-laccase as the cofactor to yield the holo-enzyme. The temperature
      dependent catalytic activity of the laccase was investigated by
      spectrophotometric as well as electrochemical methods. Specifically, the
      catalytic properties of the enzyme were characterized by employing a photometric
      assay based on the oxidation of the substrate 2,2-azino-bis-(3
      ethylbenzthiazoline-6-sulfonate) (ABTS). The electroactive substrate ABTS can be
      also monitored by cyclic voltammetry, thus allowing for determination of the
      enzymatic activity electrochemically. It was found that the recombinant laccase
      exhibited higher activity as the temperature increased up to 65  degrees C.
      Spectroscopic studies of Tth-laccase based on circular dichroism and fluorescence
      measurements are consistent with a thermally stable secondary structure of the
      protein.

PMID- 21076917
TI  - Comparison of endoglucanase-1 (EG1) induction in the edible straw mushroom
      Volvariella volvacea by lactose and/or cellobiose with or without added sorbose.
AB  - We have compared the induction of an endoglucanase (EG1) by alpha-lactose and/or
      cellobiose, with or without added L-sorbose, in submerged cultures of Volvariella
      volvacea, to better understand the mechanism whereby cellulase formation is
      triggered by these soluble disaccharides. EG1 levels induced by alpha-lactose and
      cellobiose were 28.6% and 6.7%, respectively of the highest levels recorded with
      crystalline cellulose. Sorbose did not induce EG1 and strongly repressed enzyme
      levels when added to alpha-lactose but not cellobiose-containing cultures. EG1
      levels in cultures containing all three saccharides were similar to those
      recorded with sorbose and cellobiose although enzyme induction was delayed by 12
      h. When V. volvacea was pre-grown for 24 h in medium containing sorbose as the
      sole carbon source, followed by addition of alpha-lactose or cellobiose or a
      mixture of the two, EG1 levels recorded in the alpha-lactose-supplemented
      cultures were again markedly lower compared with cultures containing only alpha
      lactose. Maximal enzyme levels in cultures with added cellobiose or cellobiose
      and alpha-lactose were not affected although appearance of EG1 in culture
      supernatants was again delayed by 12 h. Semi-quantitative RT-PCR revealed that
      higher, more prolonged, levels of eg1 transcription occurred in V. volvacea
      cultures induced with alpha-lactose compared with cellobiose- or alpha-lactose +
      cellobiose-induced cultures. However, eg1 transcription levels in cultures
      induced with cellobiose or with cellobiose + lactose, and the corresponding
      cultures with added sorbose, were not markedly different.

PMID- 21076918
TI  - Quantitative study of lipase secretion, extracellular lipolysis, and lipid
      storage in the yeast Yarrowia lipolytica grown in the presence of olive oil:
      analogies with lipolysis in humans.
AB  - Lipase secretion, extracellular lipolysis, and fatty acid uptake were quantified
      in the yeast Yarrowia lipolytica grown in the presence of olive oil and/or
      glucose. Specific lipase assays, Western blot analysis, and ELISA indicated that
      most of the lipase activity measured in Y. lipolytica cultures resulted from the
      YLLIP2 lipase. Lipase production was triggered by olive oil and, during the first
      hours of culture, most of the lipase activity and YLLIP2 immunodetection remained
      associated with the yeast cells. YLLIP2 was then released in the culture medium
      before it was totally degraded by proteases. Olive oil triglycerides were largely
      degraded when the lipase was still attached to the cell wall. The fate of
      lipolysis products in the culture medium and inside the yeast cell, as well as
      lipid storage, was investigated simultaneously by quantitative TLC-FID and GC
      analysis. The intracellular levels of free fatty acids (FFA) and triglycerides
      increased transiently and were dependent on the carbon sources. A maximum fat
      storage of 37.8% w/w of yeast dry mass was observed with olive oil alone. A
      transient accumulation of saturated FFA was observed whereas intracellular
      triglycerides became enriched in unsaturated fatty acids. So far, yeasts have
      been mainly used for studying the intracellular synthesis, storage, and
      mobilization of neutral lipids. The present study shows that yeasts are also
      interesting models for studying extracellular lipolysis and fat uptake by the
      cell. The quantitative data obtained here allow for the first time to establish
      interesting analogies with gastrointestinal and vascular lipolysis in humans.

PMID- 21076919
TI  - Microvinification--how small can we go?
AB  - High-throughput methodologies to screen large numbers of microorganisms
      necessitate the use of small-scale culture vessels. In this context, an
      increasing number of researchers are turning to microtiter plate (MTP) formats to
      conduct experiments. MTPs are now widely used as a culturing vessel for
      phenotypic screening of aerobic laboratory cultures, and their suitability has
      been assessed for a range of applications. The work presented here extends these
      previous studies by assessing the metabolic footprint of MTP fermentation. A
      comparison of Chardonnay grape juice fermentation in MTPs with fermentations
      performed in air-locked (self-induced anaerobic) and cotton-plugged (aerobic)
      flasks was made. Maximum growth rates and biomass accumulation of yeast cultures
      grown in MTPs were indistinguishable from self-induced anaerobic flask cultures.
      Metabolic profiles measured differed depending on the metabolite. While glycerol
      and acetate accumulation mirrored that of self-induced anaerobic cultures,
      ethanol accumulation in MTP ferments was limited by the increased propensity of
      this volatile metabolite for evaporation in microlitre-scale culture format. The
      data illustrates that microplate cultures can be used as a replacement for self
      induced anaerobic flasks in some instances and provide a useful and economical
      platform for the screening of industrial strains and culture media.

PMID- 21076920
TI  - Cardiopulmonary resuscitation and associated anatomic and hemodynamic changes in
      the vena cava: risk factors for inferior vena cava filter migration?

PMID- 21076921
TI  - Transcatheter arterial chemoembolization (TACE) or embolization (TAE) for
      symptomatic bone metastases as a palliative treatment.
AB  - PURPOSE: This study was designed to evaluate the effect of transcatheter arterial
      chemoembolization (TACE)/embolization (TAE) for symptomatic bone metastases
      especially in palliation. METHODS: Between April 2006 and December 2009, 24 bone
      metastatic lesions of 18 patients (8 women and 10 men; mean age, 64 years)
      underwent palliative TACE or TAE. A total of 40 sessions were performed, with 1-4
      sessions per lesion. The primary lesions included hepatocellular carcinoma,
      colorectal cancer, renal cell cancer, ovarian cancer, thyroid cancer, uterine
      cervical cancer, and esophageal cancer. Symptomatic lesions involved thoracic
      spine, lumbar spine, pelvis, rib, and femur. The procedures were performed with a
      coaxial catheter technique to catheterize selectively target arteries. If not
      possible due to small branches, blood flow alteration by coil was achieved.
      Gelatin sponge was the initial embolic materials. As anti-cancer agents,
      epirubicin, fluorouracil, and mitomycin were mainly used in consideration for
      primary lesion and past treatment. RESULTS: Sufficient devascularization of
      targeted lesions was obtained in 18 of 24 (75%) lesions without any serious
      complication. Pain relief was obtained in 20 lesions (83%), with significantly
      decrease in the visual analogue scale score (P < 0.001). A relationship was found
      between the devascularization grade and pain relief (r = 0.49, P < 0.05). Follow
      up CT images at 1 month of nine lesions (50%) revealed necrotic change in the
      tumors. CONCLUSIONS: Palliative TACE/TAE for symptomatic bone metastases could be
      a suitable treatment method because it is minimally invasive, repeatable,
      effective, and rapid-acting.

PMID- 21076922
TI  - Acute pancreatitis after percutaneous mechanical thrombectomy: case report and
      review of the literature.
AB  - PURPOSE: We describe a case of severe acute pancreatitis after percutaneous
      mechanical thrombectomy (PMT) and review the literature for the occurrence of
      this complication. MATERIALS AND METHODS: A 53-year-old man with a history of
      bilateral external iliac artery stent placement sought care for acute onset of
      lifestyle-limiting left claudication. Angiography confirmed left external iliac
      stent occlusion, and PMT with the AngioJet Xpeedior catheter (Possis Medical,
      Minneapolis MN) was performed. RESULTS: After PMT of the occluded external iliac
      artery, a residual in-stent stenosis required the placement of a second iliac
      stent. The procedure was complicated by severe acute pancreatitis. Other causes
      of pancreatitis were eliminated during the patient's hospital stay. A literature
      review revealed nine cases of acute pancreatitis after PMT. CONCLUSION: Although
      rare, pancreatitis can be a devastating complication of PMT. The development of
      pancreatitis seems to be related to the products of extensive hemolysis
      triggering an inflammatory process. To prevent this complication, we recommend
      that close attention be paid to the duration and extent of PMT, thereby avoiding
      extensive hemolysis and subsequent complications.

PMID- 21076923
TI  - Acute myocardial infarction with occlusion of all three main epicardial coronary
      arteries: when Mother Nature takes care more than physicians.
AB  - Double-arterial coronary stent thrombosis in acute myocardial infarction (AMI) is
      an infrequent but severe complication, especially when the third main coronary
      artery is chronically occluded. The conus artery (CA) can serve as a major source
      of collateral when the left anterior descendent coronary artery (LAD) becomes
      obstructed. We report a case of a 48-year-old man presenting with AMI due to a
      very late double-arterial stent thrombosis (ST) following drug-eluting stent
      implantation and a chronic occlusion of LAD collateralized by a large anomalous
      CA, which provided for the entire vascularization of the coronary tree.

PMID- 21076924
TI  - Myomectomy using purse-string suture during cesarean section.
AB  - BACKGROUND: Conventionally, myomectomy during cesarean section is reserved only
      for pedunculated myomas because resection of myomas at the time of cesarean
      section usually stimulates profuse bleeding. CASES: Thirty-one patients underwent
      myomectomy using purse-string suture during cesarean section. Myoma could be
      excised without profuse bleeding, while an assistant maintains strong tension on
      the purse-string suture around the myoma. The suture was tightened and tied
      immediately after complete resection of the myoma and then stitches of another
      purse-string suture were placed alternately with each previous stitch in the
      inner side of the first suture. We have used this method for more than 3 years
      and have not observed failures and serious complications, such as late hemorrhage
      and uterine rupture during a subsequent pregnancy. CONCLUSION: Myomectomy using
      purse-string suture during cesarean section is a safe, useful, and convenient
      technique.

PMID- 21076925
TI  - Obesity and oxidative stress: a direct link to preeclampsia?
AB  - Overweight is associated with alterations in lipid concentrations and an
      activation of inflammatory markers and both of these metabolic abnormalities are
      characteristic of preeclamptic pregnancies before the onset of clinically evident
      disease. Reactive oxygen species, particularly superoxide anions, evoke
      endothelial cell activation through many pathways. Markers of lipid peroxidation,
      including malondialdehyde and 8-epiprostaglandin-F2alpha, is increased in the
      plasma of women with preeclampsia, and the low concentrations of water- and lipid
      soluble antioxidants in the plasma and the placenta further suggest a state of
      oxidative stress. This review focuses in the relation between maternal obesity,
      oxidative stress with development of preeclampsia.

PMID- 21076927
TI  - Transient oculomotor nerve palsy after topical administration of intracisternal
      papaverine.

PMID- 21076926
TI  - Comprehensive needs assessment tool in cancer (CNAT): the development and
      validation.
AB  - PURPOSE: Needs assessment is an important step toward quality and patient
      centered cancer care, as it identifies patient need, guiding evidence-based
      cancer care policy, and maximizing care outcome. This study reports on the
      development and validation of comprehensive needs assessment tool in cancer
      (CNAT). METHODS: The CNAT, 59-item needs assessment tool for cancer was developed
      and validated in a large scale multi-center survey involving 2,661 cancer
      patients in ten fairly distributed cancer centers throughout Korea. RESULTS: To
      ensure content validity of the CNAT, items were derived from major needs
      assessment tools and input from experts and patients. Exploratory factor analysis
      confirmed its construct validity and identified seven factors: health care staff,
      psychological problems, physical symptoms, information, social and
      religious/spiritual support, practical support, and hospital facilities/services.
      Cronbach's alpha for the scale was 0.97, and for subscales, it varied from 0.80
      to 0.97. Convergent validity was demonstrated by its significant association with
      the EQ5D. Patients with elevated stress, depressive episodes, or suicidal
      ideation reported a significantly higher level of psychological and overall need.
      Known-group validity was also supported by its ability to detect significant
      differences according to age, gender, education, insurance status, months since
      diagnosis, and non-surgical anticancer treatment. Needs differed according to
      SEER stage and cancer type: advanced stage and breast and lung cancer were
      associated with a greater level of need. CONCLUSIONS: The CNAT constitutes a
      meaningful and valid response to the challenges of cancer care, enabling
      assessment of need in cancer with a comprehensive yet concise and
      psychometrically sound tool.

PMID- 21076930
TI  - Serum C-reactive protein (CRP) and procalcitonin (PCT) levels and kinetics in
      patients with leptospirosis.

PMID- 21076928
TI  - Nasal carriage of Staphylococcus aureus in healthy humans with different levels
      of contact with animals in Tunisia: genetic lineages, methicillin resistance, and
      virulence factors.
AB  - Nasal swabs of 423 healthy humans who showed different levels of contact with
      animals (frequent, 168; sporadic, 94; no contact, 161) were obtained in Tunisia
      (2008-2009), and 99 of them presented other associated risk factors. Methicillin
      resistant Staphylococcus aureus (MRSA) was detected in one of these 423 samples
      (0.24%), retrieved from a veterinarian. The MRSA isolate was mecA-positive, typed
      as ST80-t203-SCCmecIVc-agrIII, and contained tet(K), ant(6)-Ia, and aph(3')-IIIa
      genes encoding tetracycline, streptomycin, and kanamycin resistance,
      respectively. This MRSA isolate also contained the lukF/lukS virulence gene
      encoding Panton-Valentine leukocidin. Fifty-four (12.8%) additional nasal samples
      contained methicillin-susceptible S. aureus (MSSA) and one isolate/sample was
      characterized. A high diversity of spa types (n = 43; 4 new) and pulsed-field gel
      electrophoresis (PFGE) types (n = 37) was detected among the 55 recovered S.
      aureus strains. The percentages of antimicrobial resistance/detected resistance
      genes were as follows: tetracycline [22%/tet(K)-tet(L)-tet(M)], erythromycin
      [5%/msrA], ciprofloxacin [14.5%], trimethoprim-sulfamethoxazole [2%/dfrA],
      streptomycin [11%/ant(6)-Ia], kanamycin [7%/aph(3')-IIIa], amikacin [5%], and
      chloramphenicol [2%]. Four and two isolates carried the lukF/lukS and eta and/or
      etb genes, respectively, and always in individuals with contact with animals.
      Eleven isolates carried the tst gene and were recovered from individuals with
      different levels of contact with animals.

PMID- 21076929
TI  - Multiplex PCR to determine Streptococcus pneumoniae serotypes causing otitis
      media in the Republic of Ireland with further characterisation of antimicrobial
      susceptibilities and genotypes.
AB  - The purpose of this study was to determine the serotypes, genotypes and
      antimicrobial susceptibilities of Streptococcus pneumoniae causing otitis media
      (OM) in children in Dublin, Ireland. S. pneumoniae isolates (n = 28) from
      spontaneously discharging OM were studied. Serotyping was performed using a
      previously undescribed multiplex polymerase chain reaction (PCR) scheme in
      combination with serological methods. Multilocus sequence typing (MLST) was
      performed using standard procedures. Antimicrobial susceptibility testing was
      performed using the Etest method. Fourteen different S. pneumoniae serotypes were
      identified. The five most common serotypes were 3, 19F, 19A, 14 and 6A, which
      accounted for 68% of all infections. The 7-valent pneumococcal conjugate vaccine
      (PCV7), 10-valent pneumococcal conjugate vaccine (PHiD-CV) and 13-valent
      pneumococcal conjugate vaccine (PCV13) provided potential coverages of 43%, 46%
      and 86%, respectively. Reduced susceptibility to penicillin was evident for 25%
      of isolates and was associated with serotypes 14, 19A, 19F and 9V. A total of 21
      different sequence types (STs) were identified. Pneumococcal Molecular
      Epidemiology Network (PMEN) clones or their variants represented 54% (15/28) of
      all isolates. Continued monitoring and characterisation of S. pneumoniae causing
      OM in Ireland is warranted in order to guide future vaccine and treatment
      policies.

PMID- 21076931
TI  - Differences in individual empowerment outcomes of socially disadvantaged women:
      effects of mode of participation and structural changes in a physical activity
      promotion program.
AB  - OBJECTIVES: This study explored the differences in individual empowerment
      outcomes of a group of socially disadvantaged women participating in physical
      activity promotion. The outcomes observed were assessed in the context of the
      women's mode of participation and the structural organizational and community
      level changes, which took place during the implementation of the program.
      METHODS: Fifteen semi-structured qualitative interviews were conducted and
      analyzed using qualitative content analysis. Two groups of women participated in
      the interviews--those involved in the whole process of planning, implementation
      and evaluation of the program and those who took part in the program activities.
      RESULTS: Individual empowerment outcomes were achieved for all those interviewed,
      although those participating in the planning, implementation and evaluation of
      the program achieved the greatest. A number of organizational and community level
      processes were also identified that supported the individual empowerment of those
      taking part. CONCLUSIONS: This study supports the use of multilevel empowerment
      approaches to health as they help to identify the ideal characteristics that
      organizations and communities should possess and the potential structural changes
      required to support individual empowerment.

PMID- 21076932
TI  - The relationship between social support, shared decision-making and patient's
      trust in doctors: a cross-sectional survey of 2,197 inpatients using the Cologne
      Patient Questionnaire.
AB  - OBJECTIVES: Empirical studies have confirmed that a trusting physician-patient
      interaction promotes patient satisfaction, adherence to treatment and improved
      health outcomes. The objective of this analysis was to investigate the
      relationship between social support, shared decision-making and inpatient's trust
      in physicians in a hospital setting. METHODS: A written questionnaire was
      completed by 2,197 patients who were treated in the year 2000 in six hospitals in
      Germany. Logistic regression was performed with a dichotomized index for
      patient's trust in physicians. RESULTS: The logistic regression model identified
      significant relationships (p < 0.05) in terms of emotional support (standardized
      effect coefficient [sc], 3.65), informational support (sc, 1.70), shared decision
      making (sc, 1.40), age (sc, 1.14), socioeconomic status (sc, 1.15) and gender
      (sc, 1.15). We found no significant relationship between 'tendency to excuse' and
      trust. The last regression model accounted for 49.1% of Nagelkerke's R-square.
      CONCLUSIONS: Insufficient physician communication skills can lead to extensive
      negative effects on the trust of patients in their physicians. Thus, it becomes
      clear that medical support requires not only biomedical, but also psychosocial
      skills.

PMID- 21076933
TI  - Socio-economic status and psychosocial functioning of internally displaced
      adolescents and adolescents from Belgrade.
AB  - OBJECTIVES: This study aimed at investigating the differences between internally
      displaced adolescents and adolescents from Belgrade in relation to socio-economic
      status and psychosocial functioning. METHODS: The investigation was conducted in
      Belgrade in 2000 and comprised 560 high school adolescents aged 18.1 +/- 0.9
      years (response rate 88%)--32 participants were internally displaced from Kosovo
      1 year after the NATO campaign in Serbia (1999) and 528 were adolescents who
      lived in Belgrade more than 10 years. A specific questionnaire was used to obtain
      data on employment of family members, housing conditions, socialization, school
      success, smoking, alcohol consumption, and psychoactive substance use. Cornell
      Medical Index was applied as the screening test for neuroticism. RESULTS:
      Internally displaced adolescents had poorer housing conditions (p < 0.001),
      poorer school social relations (p < 0.001), and their school achievement was
      inferior (p < 0.002). The compared groups did not significantly differ in the
      frequency of smoking, alcohol consumption, psychoactive substance use, and
      neuroticism. CONCLUSION: Significant differences observed between internally
      displaced adolescents and adolescents from Belgrade in some components of both
      socioeconomic status and psychosocial functioning suggest adverse effects of
      displacement.

PMID- 21076935
TI  - Posttraumatic growth in young adults who experienced serious childhood illness: a
      mixed-methods approach.
AB  - Sixty young adult survivors of a serious childhood illness completed quantitative
      and qualitative measures assessing the relationship between specific disease and
      distress factors and posttraumatic growth (PTG). Individuals who had recovered
      from their illness reported greater growth than those who were currently
      experiencing their illness. The regression model accounted for 47% of the
      variance in PTG, with perceived severity, illness status, and posttraumatic
      stress symptoms emerging as significant predictors. Qualitative analyses
      identified salient positive and negative factors associated with having had an
      illness, such as a positive shift in perspective and frequent medical
      requirements. Being past the daily demands of illness management may allow for
      greater PTG. Realization of positive aspects of having had an illness may require
      prompting.

PMID- 21076934
TI  - Toward better QSAR/QSPR modeling: simultaneous outlier detection and variable
      selection using distribution of model features.
AB  - Building a robust and reliable QSAR/QSPR model should greatly consider two
      aspects: selecting the optimal variable subset from a large pool of molecular
      descriptors and detecting outliers from a pool of samples. The two problems have
      the specific similarity and complementarity to some extent. Given a particular
      learning algorithm on a particular data set, one should consider how the
      interaction could happen between variable selection and outlier detection. In
      this paper, we describe a consistent methodology for simultaneously performing
      variable subset selection and outlier detection using the idea of statistical
      distribution which can be simulated by the establishment of many cross-predictive
      linear models. The approach exploits the fact that the distribution of linear
      model coefficients provides a mechanism for ranking and interpreting the effects
      of variable, while the distribution of prediction errors provides a mechanism for
      differentiating the outliers from normal samples. The use of statistic of these
      distributions, namely mean value and standard deviation, inherently provides a
      feasible way to effectively describe the information contained by the original
      samples. Several examples are used to demonstrate the prediction ability of our
      proposed approach through the comparison of different approaches as well as their
      combinations.

PMID- 21076936
TI  - Luteolin prevents LPS-induced TNF-alpha expression in cardiac myocytes through
      inhibiting NF-kappaB signaling pathway.
AB  - Luteolin, a plant flavonoid, has been shown to suppress inflammatory responses;
      however, the mechanism of luteolin on cardiac myocyte inflammation is still
      unknown. Because tumor necrosis factor-alpha (TNF-alpha), an inflammatory
      cytokine, is elevated in the failing heart and exerts multiple potentially
      harmful effects on cardiac myocytes, we therefore sought to examine the effects
      of luteolin on the expression of TNF-alpha in neonatal rat cardiac myocytes. In
      the present study, enzyme-linked immunosorbent assay (ELISA), real-time PCR,
      immunoblot, immunochemistry staining, and electrophoretic mobility shift assays
      (EMSA) were performed. ELISA assay showed that luteolin decreased
      lipopolysaccharide (LPS)-induced production of TNF-alpha in the medium. Real-time
      PCR assay confirmed that luteolin also inhibited LPS-induced increase in TNF
      alpha mRNA in myocytes. Furthermore, immunoblot and immunochemistry staining
      assays represented that luteolin blocked LPS-induced IkappaB-beta degradation and
      NF-kappaB p65 subunit nuclear translocation. In addition, EMSA demonstrated that
      luteolin reduced LPS-induced NF-kappaB DNA binding activity. Luteolin protects
      against LPS-induced TNF-alpha expression via inhibition of the NF-kappaB
      signaling pathway, suggesting that luteolin may be a potential therapeutic agent
      for the treatment of inflammation-related myocardial diseases.

PMID- 21076937
TI  - Experimental investigation of HGF inhibiting glial scar in vitro.
AB  - To study the inhibitory effect of Hepatocyte growth factor (HGF) on the
      responsive hyperplasia of damaged astrocytes in vitro. We prepared damaged model
      of astrocytes to simulate the responsive hyperplasia of damaged astrocytes in
      vivo by culturing astrocytes in vitro; After the first day of Ad-HGF
      transfection, astrocytes were scratched, then after the first, the third, and the
      fifth day of scratch, we detect the expression amount of astrocytes specific
      glial fibrillary acidic protein (GFAP) and the ratio of S-phase cells with flow
      cytometry, both of which can reflect the proliferation status of damaged
      astrocytes; After HGF was added in scratched astrocytes, the activity of SPK and
      MAPK (P42/44) were detected by autoradiography and immunoblotting test; After
      adding different concentrations of HGF protein in astrocytes cultured in
      different serum concentrations and adding diverse concentrations of HGF protein,
      SPK and SPK inhibitor DMS in scratched astrocytes, we detect cell proliferation
      with 3H-TDR incorporation. The first day after Ad-HGF transfected astrocytes were
      scratched, the amount of GFAP secreted by astrocytes were decreased significantly
      (P < 0.05), and the cells in S phase were declined obviously. HGF has
      bidirectional regulation on SPK of scratched astrocytes: increases the SPK
      activity when HGF in low dose, while inhibits when in high dose. In addition, DMS
      can block the signal passage; HGF had no effects on MAPK (P42/44) of damaged
      astrocytes cells. In conclusion, after the transfection of Ad-HGF, it can inhibit
      the responsive hyperplasia of damaged astrocytes by the means of blocking SPK
      passage.

PMID- 21076938
TI  - Inhibition of tumor cell migration and invasion through knockdown of Rac1
      expression in medulloblastoma cells.
AB  - Medulloblastoma is one of the common malignant brain tumors in children or young
      adults and its overall disease-free 5-year survival rate is approximately 50% due
      to tumor progression, invasion, and metastasis. This study aimed to determine
      whether one of Rho GTPases, Rac1 can affect the morphology, motility, and
      invasion of medulloblastoma cells through knockdown of Rac1 expression.
      Medulloblastoma Daoy cells were used to manipulate Rac1 expression using Rac1
      shRNA, Rac1N17, and Rac1L61 constructs. Reverse transcriptase-PCR and western
      blot were used to detect expression of Rac1 mRNA and protein, respectively.
      Invasion and migration assays were performed to assess invasion and migration
      capacity of Daoy cells, respectively. The data showed that Rac1 mRNA and protein
      were overexpressed in Daoy cells. Deletion of Rac1 decreased the cross-linked
      actin network and pseudopodia and also inhibited the number of migration cells
      migrated or invaded to the other side of the filter compared to control cells.
      These data indicated that the invasion and migration in Daoy cells were inhibited
      by deletion of Rac1, and suggest that targeting Rac1 by Rac1 shRNA may further be
      evaluated and used as a potential anticancer strategy to treat medulloblastoma.

PMID- 21076939
TI  - Cadmium and lead uptake by Salix viminalis under modified Ca/Mg ratio.
AB  - The studies were focused on the influence of mutual changes in the ratio of
      calcium and magnesium in soil on the efficiency of cadmium and lead uptake and
      accumulation by Salix viminalis. In the environmental experiment the soil was
      modified according to the natural Ca/Mg ratio with the experimental groups 4:1
      (physiological ratio), 20:1, and 1:10, and was characterized by the amounts of
      the most important elements (including heavy metals) and selected soil
      parameters. Efficiency of lead and cadmium accumulation was in the order of Ca/Mg
      ratios 1:10 > 4:1 > 20:1, and was higher in the shoots at 0.5 m height when
      compared to 0.1 m above the ground. Under Cd and Pb supplementation the level of
      both metals was 2-fold higher, while bioaccumulation factor values according to
      selected literature indicated weak accumulation. When the seasonal metal uptake
      was analysed (from April to October), the highest accumulation efficiency was
      observed in the first two periods (April to August) and was Ca/Mg ratio
      independent. Salix growth was restrained under 1:10 Ca/Mg ratio while it was
      stimulated under 20:1 ratio, which was opposite to the metal sorption. Summing
      up, increased calcium level in soil (20:1 Ca/Mg) resulted in limited sorption of
      heavy metals and stimulated biomass productivity. Under increased magnesium
      concentration (1:10 Ca/Mg) in relation to the natural 4:1 ratio the accumulation
      efficiency was the greatest but plant growth was inhibited.

PMID- 21076941
TI  - Levels of selected minerals, nitric oxide, and vitamins in aborted Sakis sheep
      raised under semitropical conditions.
AB  - The serum levels of calcium, phosphorus, magnesium, copper, zinc and iron and of
      nitric oxide, retinol, and beta-carotene were determined in Sakiz ewes that had
      experienced an abortion and in healthy controls. Ten healthy and 25 aborted Sakiz
      sheep were selected from Afyon zone in western Turkey. Their ages ranged between
      2 and 4 years weighing between 40 and 60 kg at the time of experiment. All of the
      abortions occurred in October. The concentrations of retinol, beta-carotene,
      phosphorus, and zinc were significantly lower and those of calcium and nitric
      oxide were increased in aborted ewes relative to healthy controls. The serum
      levels of iron, copper, and magnesium were not significantly different among the
      two groups. In conclusion, abortion is an important problem in commercially
      important species of ruminants in many regions in the tropics including of
      western Turkey. Deficiencies of retinol, beta-carotene, phosphorus and zinc, and
      the increase of calcium and nitric oxide concentration may play an important role
      in the etiology of abortion in ewes. Prophylactic measures such as vitamin and
      mineral supplementation may be of help to prevent or reduce the incidence of
      abortion in sheep.

PMID- 21076940
TI  - Blood lead levels and delta-ALAD inhibition in nestlings of Eurasian Eagle Owl
      (Bubo bubo) to assess lead exposure associated to an abandoned mining area.
AB  - In order to biomonitor lead contamination in Southeastern Spain, 218 blood
      samples from 28 to 30-day old Eurasian Eagle Owl chicks (Bubo bubo) born between
      2003 and 2007 were analysed. In general, mean lead levels showed that chicks were
      exposed to background concentrations. However, mean levels in chicks born in an
      ancient and abandoned mining site ("Sierra Minera Cartagena-La Union") or in
      their surroundings (Geometric mean (GM) = 5.83 MUg/dl, range 0.49-25.61 MUg/dl),
      an area highly polluted by lead and other metals, were significantly higher (p <
      0.001) than the rest of the population (GM = 1.66 MUg/dl, range = Non detected
      18.37 MUg/dl). Because delta-ALAD activity is considered the best biomarker for
      lead exposure and effect in birds, the activity of this enzyme was also evaluated
      and correlated with lead levels in blood. In this study, low levels of blood lead
      inhibited delta-ALAD, even when lead concentrations were lower than the limits
      described by other authors in raptors. Adverse effects caused by this inhibition
      may occur when blood lead levels were above 15 MUg/dl, although only eight chicks
      presented these concentrations in their blood. Sampling site also influenced
      enzymatic activity, since it decreased about 60% in the polluted area in relation
      to the rest. For all these reasons, further research regarding risk assessment
      for lead exposure in Eagle Owls nesting in the polluted area is advisable. Our
      results suggest that the Eurasian Eagle Owl can be considered a suitable sentinel
      animal for monitoring lead contamination and delta-ALAD activity can be used as a
      sensitive biomarker for lead exposure and effect in this species.

PMID- 21076942
TI  - Risk of malnutrition and health-related quality of life in community-living
      elderly men and women: the Tromso study.
AB  - PURPOSE: To explore the association between risk of malnutrition as well as
      current body mass index (BMI) and health-related quality of life (HRQoL) in
      elderly men and women from the general population. METHODS: In a cross-sectional
      population survey including 1,632 men and 1,654 women aged 65 to 87 years from
      the municipality of Tromso, Norway, we assessed HRQoL by using the EuroQol (EQ
      5D) instrument in three risk groups of malnutrition and in different categories
      of BMI. The Malnutrition Universal Screening Tool ('MUST') was used to evaluate
      the risk of malnutrition. RESULTS: We found a significant reduction in HRQoL with
      an increasing risk of malnutrition, and this was more pronounced in men than in
      women. The relationship between BMI and HRQoL was dome shaped, with the highest
      score values in the BMI category being 25-27.5 kg/m(2). CONCLUSIONS: HRQoL was
      significantly reduced in elderly men and women at risk of malnutrition. The
      highest HRQoL was seen in moderately overweight individuals.

PMID- 21076943
TI  - Evaluation of ERCC1 expression for cisplatin sensitivity in human hepatocellular
      carcinoma.
AB  - BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) is one of the
      key enzymes in DNA repair. This study was designed to investigate the correlation
      between ERCC1 expression and chemosensitivity to cisplatin (CDDP) in patients
      with hepatocellular carcinoma (HCC). METHODS: Eighty-seven HCC samples were
      analyzed by immunohistochemistry for ERCC1 and chemosensitivity was assessed by
      the succinate dehydrogenase inhibition (SDI) test for four anti-cancer agents,
      including CDDP. The ERCC1 expression was examined in HCC cell lines. ERCC1 siRNA
      was transfected to PLC/RPF/5 to investigate the correlation of ERCC1 expression
      and CDDP sensitivity. RESULTS: ERCC1 expression was observed in 33% of nuclei in
      immunohistochemical examination. Patients were divided into two groups as
      follows: ERCC1 high expression group (n = 43): more than 33% of the nuclei were
      stained; ERCC1 low expression group (n = 44): 33% or fewer of the nuclei were
      stained. Tumor size of low expression group was larger than that in the high
      expression group (p = 0.02). The succinic dehydrogenase (SD) activity only for
      CDDP was significantly higher in the high expression group than that in the low
      expression group (p = 0.02). An increased expression of ERCC1 was shown by
      immunohistochemical and Western blot analyses in PLC/RPF/5. ERCC1 expression was
      inhibited by ERCC1 siRNA transfection and the LC50 value (nM) of CDDP was reduced
      from 25.7 to 12.5 (p = 0.01). CONCLUSIONS: Increased ERCC1 expression is
      associated with CDDP resistance in HCC specimens and cell lines. Therefore,
      immunohistochemical analysis for resected HCC tissues may be a useful predictor
      for the effectiveness of adjuvant chemotherapy, using CDDP.

PMID- 21076945
TI  - The syntheses and characterization of molecularly imprinted polymers for the
      controlled release of bromhexine.
AB  - Imprinted polymers are now being increasingly considered for active biomedical
      uses such as drug delivery. In this work, the use of molecularly imprinted
      polymers (MIPs) in designing new drug delivery devices was studied. Imprinted
      polymers were prepared from methacrylic acid (functional monomer), ethylene
      glycol dimethacrylate (cross-linker), and bromhexine (as a drug template) using
      bulk polymerization method. The influence of the template/functional monomer
      proportion and pH on the achievement of MIPs with pore cavities with a high
      enough affinity for the drug was investigated. The polymeric devices were further
      characterized by FT-IR, thermogravimetric analysis, scanning electron microscopy,
      and binding experiments. The imprinted polymers showed a higher affinity for
      bromhexine and a slower release rate than the non-imprinted polymers. The
      controlled release of bromhexine from the prepared imprinted polymers was
      investigated through in vitro dissolution tests by measuring absorbance at lambda
      (max) of 310 nm by HPLC-UV. The dissolution media employed were hydrochloric acid
      at the pH level of 3.0 and phosphate buffers, at pH levels of 6.0 and 8.0,
      maintained at 37.0 and 25.0 +/- 0.5  degrees C. Results from the analyses showed
      the ability of MIP polymers to control the release of bromhexine In all cases The
      imprinted polymers showed a higher affinity for bromhexine and a slower release
      rate than the non-imprinted polymers. At the pH level of 3.0 and at the
      temperature of 25  degrees C, slower release of bromhexine imprinted polymer
      occurred.

PMID- 21076944
TI  - Selectively hydrogenated soybean oil exerts strong anti-prostate cancer
      activities.
AB  - Prostate cancer is the second leading cause of male deaths due to cancer in the
      United States. Hydrogenated vegetable oils have been suspected of inducing
      adverse health effects, including atherosclerosis and cancer. Here we report that
      a selectively hydrogenated soybean oil (SHSO) containing a high quantity of
      conjugated linoleic acids showed remarkably strong anticarcinogenic activity
      against prostate cancer in the rat model (Copenhagen rats with MAT-LyLu syngeneic
      rat prostate cancer cells) study in vivo and human prostate carcinoma cell lines
      studies in vitro, as compared with native soybean oil. A 5% dietary
      supplementation with SHSO inhibited the growth of prostate cancer by 80% in vivo.
      The TUNEL method and immunohistochemical staining assays of bax, bcl-2, and
      survivin clearly showed that SHSO induced prostate cancer cell apoptosis in the
      tested rats. DNA fragmentation analysis in vitro further confirmed the apoptotic
      activity of SHSO on the MAT-LyLu prostate cancer cells. The SHSO also showed
      strong cytotoxicity on human prostate cancer cells (DU145 and PC3). This
      represents the first report demonstrating the significant anticancer activities
      of hydrogenated vegetable oils at low levels of dietary supplementation.

PMID- 21076946
TI  - A case of homicidal intraoral gunshot and review of the literature.
AB  - Determination of the manner of death in case of intraoral firearm wounds can be a
      challenge, especially if the circumstances of the incident are unclear and crime
      scene investigation is inadequate. It is a well-known fact that the mouth is one
      of the selected sites for suicide with firearms. Homicidal shooting through the
      mouth is said to be rare, but does occur, and can be mistaken for a suicide. For
      discrimination between suicide and homicide in cases of intraoral firearm wounds,
      some useful points are the site of entry wound, the direction of the internal
      bullet path, the range of fire and the circumstances of death. We demonstrate
      these points in a case of a homicidal gunshot to the mouth assessed by both
      classical autopsy and post-mortem CT (PMCT).

PMID- 21076947
TI  - Clinico-pathologic conference: case 2. Embryonal rhabdomyosarcoma (RMS).

PMID- 21076948
TI  - Clinico-pathologic conference: case 1. High-grade osteosarcoma (OS) and florid
      cemento-osseous dysplasia (FCOD).

PMID- 21076950
TI  - Superior glottic views with the GlideScope(r) and Airtraq(r) laryngoscopes
      compared with an anterior commissure laryngoscope.

PMID- 21076951
TI  - Transesophageal echocardiography training: looking forward to the next step.

PMID- 21076952
TI  - Use of a new task-relevant test to assess the effects of shift work and drug
      labelling formats on anesthesia trainees' drug recognition and confirmation.
AB  - BACKGROUND: Drug administration errors occur in every aspect of clinical
      practice. Using a novel task-relevant Medication Recognition and Confirmation
      Test (MRCT), we investigated the effects on performance of working night and day
      shifts and labelling different drug formats. METHODS: Anesthesia trainees (n =
      18) participated in one of two experiments during an 8-12 hr day shift and an 8
      12 hr night shift. In Experiment-1 (n = 10), we compared standardized colour
      coded labels with pictures of ampoules. In Experiment-2 (n = 8), we compared
      colour-coded labels with black and white labels. Sleep was measured with wrist
      actigraphy during both day and night shift runs over seven to eight days. The
      MRCT outcome measures were reaction times and drug errors. RESULTS: In the two
      experiments, colour-coded labels were recognized (and therefore selected) more
      quickly than pictures of conventional ampoules (mean difference 332 msec, 95%
      confidence interval (CI) 242-422 msec; P < 0.0001) and faster than black and
      white labels (mean difference 96 msec, 95% CI 46-146 msec; P < 0.0001).
      Participants obtained less sleep while working night shifts than while working
      day shifts (mean difference 57 min, 95% CI 0:15-1:39 hr; P = 0.013). Mean
      confirmation reaction times were slower during night shifts than during day
      shifts (mean difference 60 msec, 95% CI 1-120 msec; P = 0.048). No differences in
      error rates were observed between shifts or among drug label types. CONCLUSIONS:
      Label format influenced recognition and confirmation reaction times to
      representations of drugs in this study, and we found some evidence to suggest
      that performance is better during day shifts than during night shifts. The task
      relevant test evaluated here may have further application in measuring
      performance in the wider clinical setting.

PMID- 21076957
TI  - Simultaneous analysis of cardiac glycosides in blood and urine by
      thermoresponsive LC-MS-MS.
AB  - A new thermoresponsive polymer separation column was applied to simultaneous
      analysis of four cardiac glycosides (CGs) being widely used for the treatment of
      arrhythmias and heart failure in human blood and urine. This column is composed
      of an N-isopropylacrylamide polymer, the surface of which undergoes a reversible
      alteration from hydrophilic to hydrophobic by changing temperature. The
      chromatographic separation and retention times can be easily be controlled by
      adjusting the column temperature. As the column temperature was changed from 50
      to 10  degrees C over 8 min, five CGs, including deslanoside, digoxin,
      methyldigoxin, digitoxin, and digitoxigenin (internal standard) were better
      resolved. Using these LC conditions, we analyzed four CGs in human whole blood
      and urine simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS
      MS). Validation data as functions of recovery rates, linearity, accuracy, and
      precision were carefully tested; all were generally satisfactory. The detection
      limits for the four CGs in both matrices were 0.2-0.3 ng/mL. The method was
      applied to analysis of methyldigoxin and its main metabolite digoxin in whole
      blood and urine samples obtained from a deceased person in actual autopsy case.
      To our knowledge, this is the first report describing an LC-MS-MS method using a
      thermoresponsive column for analysis of drug(s). The inclusion of the
      thermoresponsive column in an LC-MS-MS technique seems to extend the possibility
      for simultaneous analysis of compounds of different properties, such as
      hydrophobic precursors and their hydrophilic metabolites in biological samples
      within limited analysis times.

PMID- 21076956
TI  - External validation of the UK Prospective Diabetes Study (UKPDS) risk engine in
      patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Treatment guidelines recommend the UK Prospective Diabetes Study
      (UKPDS) risk engine for predicting cardiovascular risk in patients with type 2
      diabetes, although validation studies showed moderate performance. The methods
      used in these validation studies were diverse, however, and sometimes
      insufficient. Hence, we assessed the discrimination and calibration of the UKPDS
      risk engine to predict 4, 5, 6 and 8 year cardiovascular risk in patients with
      type 2 diabetes. METHODS: The cohort included 1,622 patients with type 2
      diabetes. During a mean follow-up of 8 years, patients were followed for
      incidence of CHD and cardiovascular disease (CVD). Discrimination and calibration
      were assessed for 4, 5, 6 and 8 year risk. Discrimination was examined using the
      c-statistic and calibration by visually inspecting calibration plots and
      calculating the Hosmer-Lemeshow chi(2) statistic. RESULTS: The UKPDS risk engine
      showed moderate to poor discrimination for both CHD and CVD (c-statistic of 0.66
      for both 5 year CHD and CVD risks), and an overestimation of the risk (224% and
      112%). The calibration of the UKPDS risk engine was slightly better for patients
      with type 2 diabetes who had been diagnosed with diabetes more than 10 years ago
      compared with patients diagnosed more recently, particularly for 4 and 5 year
      predicted CVD and CHD risks. Discrimination for these periods was still moderate
      to poor. CONCLUSIONS/INTERPRETATION: We observed that the UKPDS risk engine
      overestimates CHD and CVD risk. The discriminative ability of this model is
      moderate, irrespective of various subgroup analyses. To enhance the prediction of
      CVD in patients with type 2 diabetes, this model should be updated.

PMID- 21076958
TI  - The sporting nature of science.

PMID- 21076959
TI  - Discriminant study of the development of the mandibular units in a neural
      reference system.
AB  - The mandible is a complex osteological structure composed of distinct units
      integrated into a single bone around the director axis of the mandibular nerve.
      In this study of the mandibular development, we use a method that synthesizes the
      contributions of each sub-unit, using the mandibular canal as reference system.
      This novel approach results in new informations and confirms the leading role of
      the mandibular nerve and of its curve in mandibular development. It would seem to
      be possible to explain a major part of mandibular development by the role of the
      nerve as guide.

PMID- 21076960
TI  - Diagnostic cross-sectional imaging of arterial diseases: really noninvasive?

PMID- 21076962
TI  - Bladder-opening technique for hysterectomy for placenta previa percreta.
AB  - The "bladder-opening" technique can be applied to cesarean hysterectomy for
      placenta previa percreta with bladder invasion. Cutting the bladder lateral wall
      with an automatic stapling/cutting apparatus enables direct visualization of the
      invaded bladder area and its resection. This may reduce the amount of hemorrhage
      and avoid accidental bladder injury.

PMID- 21076961
TI  - Brain aging and Abeta1-42 neurotoxicity converge via deterioration in autophagy
      lysosomal system: a conditional Drosophila model linking Alzheimer's
      neurodegeneration with aging.
AB  - Aging is known to be the most prominent risk factor for Alzheimer's disease (AD);
      however, the underlying mechanism linking brain aging with AD pathogenesis
      remains unknown. The expression of human amyloid beta 42 peptide (Abeta1-42), but
      not Abeta1-40 in Drosophila brain induces an early onset and progressive
      autophagy-lysosomal neuropathology. Here we show that the natural process of
      brain aging also accompanies a chronic and late-onset deterioration of neuronal
      autophagy-lysosomal system. This process is characterized by accumulation of
      dysfunctional autophagy-lysosomal vesicles, a compromise of these vesicles
      leading to damage of intracellular membranes and organelles, necrotic-like
      intraneuronal destruction and neurodegeneration. In addition, conditional
      activation of neuronal autophagy in young animals is protective while late
      activation is deleterious for survival. Intriguingly, conditional Abeta1-42
      expression limited to young animals exacerbates the aging process to a greater
      extent than Abeta1-42 expression in old animals. These data suggest that the
      neuronal autophagy-lysosomal system may shift from a functional and protective
      state to a pathological and deleterious state either during brain aging or via
      Abeta1-42 neurotoxicity. A chronic deterioration of the neuronal autophagy
      lysosomal system is likely to be a key event in transitioning from normal brain
      aging to pathological aging leading to Alzheimer's neurodegeneration.

PMID- 21076963
TI  - Hydrolyzed fish collagen induced chondrogenic differentiation of equine adipose
      tissue-derived stromal cells.
AB  - Adipose-derived stromal cells (ADSCs) are multipotent cells which, in the
      presence of appropriate stimuli, can differentiate into various lineages such as
      the osteogenic, adipogenic and chondrogenic. In this study, we investigated the
      effect of transforming growth factor beta 1 (TGF-beta1) in comparison to
      hydrolyzed fish collagen in terms of the chondrogenic differentiation potential
      of ADSCs. ADSCs were isolated from subcutaneous fat of horses by liposuction.
      Chondrogenesis was investigated using a pellet culture system. The
      differentiation medium was either supplemented with TGF-beta1 (5 ng/ml) or fish
      collagen (0.5 mg/ml) for a 3 week period. After the 3 weeks in vitro
      differentiation, RT-PCR and histological staining for proteoglycan synthesis and
      type II collagen were performed to evaluate the degree of chondrogenic
      differentiation and the formation of cartilaginous extracellular matrix (ECM).
      The differentiation of ADSCs induced by TGF-beta1 showed a high expression of
      glycosaminoglycan (GAG). Histological analysis of cultures stimulated by
      hydrolyzed fish collagen demonstrated an even higher GAG expression than cultures
      stimulated under standard conditions by TGF-beta1. The expression of cartilage
      specific type II collagen and Sox9 was about the same in both stimulated
      cultures. In this study, chondrogenesis was as effectively induced by hydrolyzed
      fish collagen as it was successfully induced by TGF-beta1. These findings
      demonstrated that hydrolyzed fish collagen alone has the potential to induce and
      maintain ADSCs-derived chondrogenesis. These results support the application of
      ADSCs in equine veterinary tissue engineering, especially for cartilage repair.

PMID- 21076964
TI  - Impairment of color vision in aircraft maintenance workers.
AB  - PURPOSE: The purpose of the study was to examine possible persisting effects to
      color vision in a group from the Royal Australian Air Force who had exposure to
      formulations containing neurotoxins during F-111 fuel tank maintenance, relative
      to two contemporaneous comparison groups. METHODS: Color vision was tested in 512
      exposed personnel, 458 technical-trade comparisons, and 330 non-technical
      comparisons using the Ishihara test plates and the Lanthony D-15 Desaturated
      Color disk arrangement test. Participants were excluded if they failed the
      Ishihara test as this indicates congenital color blindness. From the Lanthony
      results, the type of color deficient vision (CDV) was diagnosed, and
      additionally, the Bowman's color confusion index (CCI) was calculated. Regression
      models were used to examine whether there was an association between color vision
      deficiencies and F-111 fuel tank maintenance, adjusting for possible confounders.
      RESULTS: The CCI ranged from 1 to 2.8 (median 1.2, quartiles 1.1, 1.4) in the
      2,600 eyes tested. Forty five percent of all participants had blue-yellow CDV in
      at least one eye. Deficiencies of this nature are caused by environmental
      exposures. Logistic regression demonstrated statistically significant differences
      in CCI category in the exposed group versus technical group (odds ratio 1.7: 95%
      CI 1.3-2.0) and a blue-yellow confusion in the exposed group versus technical
      group (odds ratio 1.4: 95% CI 1.1-1.7). No differences were observed between the
      exposed group and the non-technical group. CONCLUSION: The results indicate
      reduced color discrimination among the exposed subjects compared to one of two
      control groups. The findings may be due to previous exposure to solvents among
      the air force personnel.

PMID- 21076965
TI  - Influence of lung parasites on the growth rates of free-ranging and captive adult
      cane toads.
AB  - Many parasites affect the viability of their hosts, but detailed studies
      combining empirical data from both the field and the laboratory are limited.
      Consequently, the nature and magnitude of such effects are poorly known for many
      important host-parasite systems, including macroparasites of amphibians. We
      examined the effects of lungworm (Rhabdias pseudosphaerocephala) infections in
      cane toads (Bufo marinus) within their invasive Australian range. The host
      specificity of this parasite suggests that it might serve as a biological control
      agent for toads in Australia, if infection proves to reduce toad viability. Mark
      recapture studies in the field (near Darwin, Northern Territory) revealed lowered
      growth rates in infected adult toads when compared to uninfected toads, and a
      laboratory experiment confirmed causality: experimental infection with R.
      pseudosphaerocephala reduce toad growth rates. In combination with previous work
      on the current host-parasite system, it is now evident that nematode lungworms
      reduce the viability of both newly metamorphosed and adult cane toads, and do so
      in the field as well as in the laboratory. Rhabdias pseudosphaerocephala may be a
      valuable component of a biological control strategy for cane toads in Australia.

PMID- 21076966
TI  - Population sinks resulting from degraded habitats of an obligate life-history
      pathway.
AB  - Many species traverse multiple habitats across ecosystems to complete their life
      histories. Degradation of critical, life stage-specific habitats can therefore
      lead to population bottlenecks and demographic deficits in sub-populations. The
      riparian zone of waterways is one of the most impacted areas of the coastal zone
      because of urbanisation, deforestation, farming and livestock grazing. We
      hypothesised that sink populations can result from alterations of habitats
      critical to the early life stages of diadromous fish that use this zone, and
      tested this with field-based sampling and experiments. We found that for Galaxias
      maculatus, one of the most widely distributed fishes of the southern hemisphere,
      obligate riparian spawning habitat was very limited and highly vulnerable to
      disturbance across 14 rivers in New Zealand. Eggs were laid only during spring
      tides, in the highest tidally influenced vegetation of waterways. Egg survival
      increased to >90% when laid in three riparian plant species and where stem
      densities were great enough to prevent desiccation, compared to no survival where
      vegetation was comprised of other species or was less dense. Experimental
      exclusion of livestock, one of the major sources of riparian degradation in rural
      waterways, resulted in quick regeneration, a tenfold increase in egg laying by
      fish and a threefold increase in survival, compared to adjacent controls.
      Overall, there was an inverse relationship between river size and egg production.
      Some of the largest rivers had little or no spawning habitat and very little egg
      production, effectively becoming sink populations despite supporting large adult
      populations, whereas some of the smallest pristine streams produced millions of
      eggs. We demonstrate that even a wide-ranging species with many robust adult
      populations can be compromised if a stage-specific habitat required to complete a
      life history is degraded by localised or more diffuse impacts.

PMID- 21076967
TI  - Aciclovir and varicella-zoster-immunoglobulin in solid-organ transplant
      recipients.
AB  - Clear recommendations for the management of acute varicella-zoster virus (VZV)
      infections for cases of significant exposure and the use of prophylactic drugs
      after solid-organ transplantation are missing due to the lack of evidence by
      prospective studies. Heterogeneity in patient groups, patient numbers, age
      groups, immunosuppressive regimens, timing, and dosage of aciclovir and/or
      varicella-zoster immunoglobulin (VZIG), pre-transplant vaccination or VZV wild
      type infection and inconsistency of data make comparability of different studies
      impossible. Although the benefit of aciclovir and/or VZIG is uncertain in
      immunosuppressed children, prospective controlled double-blind studies are not
      feasible for ethical considerations as fatal cases with disseminating varicella
      disease are well known in these patient groups despite the use of aciclovir
      and/or VZIG, whereas severe side-effects of these drugs are rare. However, a
      reporting bias is likely as mainly severe or fatal cases might have been
      predominantly published or cases of successfully used aciclovir and/or VZIG in
      mild cases or in cases of breakthrough infections after vaccination. As neither
      VZIG prophylaxis nor treatment with intravenous aciclovir offers complete
      protection against severe VZV infection to immunosuppressed pediatric solid-organ
      transplant recipients, high priority should be given to vaccination against VZV
      prior to transplantation, and, most importantly, in their close contact persons.
      Clinical observations suggest that only assessment of humoral immunity together
      with cellular immunity may allow predication about protection in exposed
      patients.

PMID- 21076969
TI  - A novel methodology independent of fermentation rate for assessment of the
      fructophilic character of wine yeast strains.
AB  - The yeast Saccharomyces cerevisiae has a fundamental role in fermenting grape
      juice to wine. During alcoholic fermentation its catabolic activity converts
      sugars (which in grape juice are a near equal ratio of glucose and fructose) and
      other grape compounds into ethanol, carbon dioxide and sensorily important
      metabolites. However, S. cerevisiae typically utilises glucose and fructose with
      different efficiency: glucose is preferred and is consumed at a higher rate than
      fructose. This results in an increasing difference between the concentrations of
      glucose and fructose during fermentation. In this study 20 commercially available
      strains were investigated to determine their relative abilities to utilise
      glucose and fructose. Parameters measured included fermentation duration and the
      kinetics of utilisation of fructose when supplied as sole carbon source or in an
      equimolar mix with glucose. The data were then analysed using mathematical
      calculations in an effort to identify fermentation attributes which were
      indicative of overall fructose utilisation and fermentation performance.
      Fermentation durations ranged from 74.6 to over 150 h, with clear differences in
      the degree to which glucose utilisation was preferential. Given this variability
      we sought to gain a more holistic indication of strain performance that was
      independent of fermentation rate and therefore utilized the area under the curve
      (AUC) of fermentation of individual or combined sugars. In this way it was
      possible to rank the 20 strains for their ability to consume fructose relative to
      glucose. Moreover, it was shown that fermentations performed in media containing
      fructose as sole carbon source did not predict the fructophilicity of strains in
      wine-like conditions (equimolar mixture of glucose and fructose). This work
      provides important information for programs which seek to generate strains that
      are faster or more reliable fermenters.

PMID- 21076968
TI  - Interspecific reproductive barriers in the tomato clade: opportunities to
      decipher mechanisms of reproductive isolation.
AB  - The tomato clade within the genus Solanum has numerous advantages for mechanistic
      studies of reproductive isolation. Its thirteen closely related species, along
      with four closely allied Solanum species, provide a defined group with diverse
      mating systems that display complex interspecific reproductive barriers. Several
      kinds of pre- and postzygotic barriers have already been identified within this
      clade. Well-developed genetic maps, introgression lines, interspecific bridging
      lines, and the newly available draft genome sequence of the domesticated tomato
      (Solanum lycopersicum) are valuable tools for the genetic analysis of
      interspecific reproductive barriers. The excellent chromosome morphology of these
      diploid species allows detailed cytological analysis of interspecific hybrids.
      Transgenic methodologies, well developed in the Solanaceae, allow the functional
      testing of candidate reproductive barrier genes as well as live imaging of pollen
      rejection events through the use of fluorescently tagged proteins. Proteomic and
      transcriptomics approaches are also providing new insights into the molecular
      nature of interspecific barriers. Recent progress toward understanding
      reproductive isolation mechanisms using these molecular and genetic tools is
      assessed in this review.

PMID- 21076970
TI  - Effect of phase delay lighting rotation schedule on daily expression of per2,
      bmal1, rev-erbalpha, pparalpha, and pdk4 genes in the heart and liver of Wistar
      rats.
AB  - Under synchronized conditions daily rhythms run in precise phase relationships.
      Long lasting shift-work disturbs circadian rhythms and causes metabolism
      dysfunction. As a result of frequent shifts of the light (L):dark (D) cycle the
      circadian system has to adjust to a new regimen repeatedly, and organism can
      never achieve complete adjustment of all circadian rhythms. Nuclear receptor
      PPARalpha is supposed to be a functional interface between circadian clock and
      metabolism, and its interconnection with rev-erbalpha and pdk4 was proven. The
      aim of this study was to elucidate responsiveness of the circadian system to the
      LD cycle mimicking the rotating shift-work with 8-h phase delay every second day.
      Expression of key clock genes and clock controlled metabolic genes rev-erbalpha,
      pparalpha, and pdk4 was analyzed in the liver and heart of rats by real time PCR.
      Control Wistar rats were exposed to the regular LD cycle 12:12. The second group
      was exposed to the LD regimen mimicking shift-work with 8-h phase delays during
      period of 10 weeks. Sampling was performed in 4-h intervals during 24-h cycle.
      Clock gene expression in the heart and liver of shifted rats was rhythmic and
      phase delayed by 8-9 h compared to control. Expression of metabolic genes was
      influenced more in the liver than in the heart. Results indicate that frequent
      shifts of LD cycle may interfere with control of lipid metabolism.

PMID- 21076971
TI  - Inhibition of penicillium digitatum and penicillium italicum in vitro and in
      planta with Panomycocin, a novel exo-beta-1,3-glucanase isolated from Pichia
      anomala NCYC 434.
AB  - Panomycocin, a novel exo-beta 1,3 glucanase, was tested as an antifungal agent
      against green and blue mold diseases, the most important causes of post harvest
      decay in citrus fruits. All tested isolates of Penicillium digitatum and
      Penicillium italicum were susceptible to panomycocin in vitro. Effective
      panomycocin concentrations for 50% growth inhibition (MIC-2) for P. digitatum and
      P. italicum were 2 and 1 microg ml(-1), respectively. Complete (MIC-0) growth
      inhibition of all isolates observed at a panomycocin concentration of 16 microg
      ml(-1). Treatment of spores with panomycocin at values lower than the MIC-0 led
      to slower germ tube elongation and mycelium growth. In tests on fruit,
      panomycocin at concentrations equal to in vitro MIC-0 value protected lemon fruit
      from decay.

PMID- 21076972
TI  - The NAMES assessment: a novel combined-modality screening tool for obstructive
      sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea (OSA) remains underdiagnosed, despite our
      understanding of its impact on general health. Current screening methods utilize
      either symptoms or physical exam findings suggestive of OSA, but not both. The
      purpose of this study was to develop a novel screening tool for the detection of
      OSA, the NAMES assessment (neck circumference, airway classification,
      comorbidities, Epworth scale, and snoring), combining self-reported historical
      factors with physical exam findings. METHODS: Subjects were adults without
      previously diagnosed OSA, referred to a community sleep center for suspicion of
      OSA. General health, Epworth Sleepiness Scale (ESS), and Berlin questionnaires
      were completed, and a physical exam focusing on modified Friedman (MF) grade,
      body mass index (BMI), and neck circumference (NC) was performed prior to
      polysomnography. OSA was defined by a respiratory disturbance index >=15. Each
      variable was dichotomized, and cutoff values were determined for the NAMES tool
      in a pilot group of 150 subjects. The NAMES score was calculated from NC, MF,
      comorbidities, ESS, and loud snoring values. The performances of the NAMES,
      Berlin questionnaire, and ESS screening tests in predicting OSA were then
      compared in a validation group of 509 subjects. RESULTS: In the pilot population,
      the cutoff value for the composite NAMES tool was calculated at >=3 points. In
      the validation group, NAMES demonstrated similar test characteristics to the
      Berlin questionnaire, and sensitivity was better than that seen with the Epworth
      scale. The addition of BMI and gender to the tool improved screening
      characteristics. CONCLUSIONS: The NAMES assessment is an effective, inexpensive
      screening strategy for moderate to severe OSA.

PMID- 21076973
TI  - Socio-demographic characteristics, health behaviour, co-morbidity and accidents
      in snorers: a population survey.
AB  - OBJECTIVE: We assessed the socio-demographic correlates of snoring and also the
      patterns of health behaviour and co-morbidity associated with different types of
      snoring in the Hungarian population. We wanted to study whether different types
      of snoring are associated with high-risk health behaviour, chronic illnesses,
      daytime consequences of poor sleep, and with frequent accidents compared with non
      snoring individuals. METHOD: This is a cross-sectional study. Interviews were
      carried out in the homes of 12,643 people. This was the largest nationally
      representative study in Central Europe about health behaviour. In the Athens
      Insomnia Scale, questions about snoring and sleep behaviour, life-style factors
      and health behaviour, as well as questions on their history and current medical
      treatment were included in the questionnaire. RESULTS: Thirty-seven percent of
      males and 21% of females reported loud snoring with breathing pauses. We found a
      significant increasing trend for the consumption of alcohol and coffee as well as
      smoking among non-snorers, habitual snorers and loud snorers, respectively. In an
      ordinal regression model male gender, the presence of smoking, the presence of
      three or more co-morbid conditions and alcohol consumption were independent
      predictors of snoring (OR [95% CI], 1.99 [1.85-2.1], 1.76 [1.60-1.92], 1.45 [1.30
      1.62] and 1.22 [1.04-1.43], respectively, P < 0.001) after controlling for
      multiple socio-demographic and clinical variables. The frequency of accidents was
      higher in the loud snoring group than among non-snoring individuals (24% vs 17%,
      P < 0.0001). CONCLUSIONS: Snoring is common in the Hungarian adult population.
      Snoring, especially loud snoring with breathing pauses, is strongly associated
      with high-risk health behaviour, higher co-morbidity and a higher frequency of
      accidents.

PMID- 21076974
TI  - Congenital central hypoventilation syndrome: four families.
AB  - BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare
      condition that usually presents soon after birth and is potentially life
      shortening if not treated. The defining abnormality is hypoventilation during
      sleep which requires life-long treatment with artificial ventilation. This
      syndrome may also be associated with generalised dysfunction of the autonomic
      nervous system and a sub-group with associated Hirschsprung's disease. The
      genetic basis of CCHS has been identified as mutations in the PHOX2B gene.
      METHODS: We present four families, three with autosomal dominant inheritance and
      familial clustering, and one with a de novo mutation resulting in CCHS.
      CONCLUSIONS: We demonstrate that nasal mask ventilation from birth can provide
      adequate treatment and improved quality of life for these children. Phenotypic
      variability in expression of disease is seen in families with the same mutations
      in PHOX2B gene. The psychosocial costs of the disease and the unrecognised
      'morbidity barter' that is part of current management needs to be factored into
      in all stages of management from childhood to adolescence to adulthood.

PMID- 21076975
TI  - Effects of exercise and physical activity on depression.
AB  - INTRODUCTION: Depression is a very prevalent mental disorder affecting 340
      million people globally and is projected to become the leading cause of
      disability and the second leading contributor to the global burden of disease by
      the year 2020. AIM: In this paper, we review the evidence published to date in
      order to determine whether exercise and physical activity can be used as
      therapeutic means for acute and chronic depression. Topics covered include the
      definition, classification criteria and treatment of depression, the link between
      beta-endorphin and exercise, the efficacy of exercise and physical activity as
      treatments for depression, properties of exercise stimuli used in intervention
      programs, as well as the efficacy of exercise and physical activity for treating
      depression in diseased individuals. CONCLUSIONS: The presented evidence suggests
      that exercise and physical activity have beneficial effects on depression
      symptoms that are comparable to those of antidepressant treatments.

PMID- 21076977
TI  - Random Leslie matrices in population dynamics.
AB  - We generalize the concept of the population growth rate when a Leslie matrix has
      random elements (correlated or not), i.e., characterizing the disorder in the
      vital parameters. In general, we present a perturbative formalism to deal with
      linear non-negative random matrix difference equations, then the non-trivial
      effective eigenvalue of which defines the long-time asymptotic dynamics of the
      mean-value population vector state is presented as the effective growth rate.
      This effective eigenvalue is calculated from the smallest positive root of a
      secular polynomial. Analytical (exact and perturbative calculations) results are
      presented for several models of disorder. In particular, a 3 * 3 numerical
      example is applied to study the effective growth rate characterizing the long
      time dynamics of a biological population model. The present analysis is a
      perturbative method for finding the effective growth rate in cases when the vital
      parameters may have negative covariances across populations.

PMID- 21076976
TI  - Relationships between C-reactive protein, white blood cell count, and insulin
      resistance in a Chinese population.
AB  - This study is to clarify whether C-reactive protein (CRP) and white blood cell
      (WBC) count influence insulin homeostasis to the same degree. Serum CRP and
      peripheral WBC were measured in 739 subjects with normal glucose regulation, 512
      with impaired glucose regulation, and 502 newly diagnosed diabetic patients.
      Levels of insulin resistance (IR) were assessed using the index of homeostasis
      model (HOMA-IR). Serum CRP and WBC were significantly correlated with HOMA-IR and
      risk factors of IR. Relative risks of IR for each 1-SD increase of Ln (CRP) and
      Ln (WBC) were 1.28 (1.10-1.47) and 1.15 (1.01-1.31), respectively after
      adjustment for age, sex, obesity measurements, and other traditional risk
      factors. Additional adjustment for WBC slightly attenuated the association
      between CRP and IR [1.25 (1.08-1.45); P = 0.003] whereas adjustment for CRP
      substantially attenuated the association of WBC with IR toward null (P = 0.134).
      Moreover, individuals with both high levels of CRP and WBC were at higher risks
      of IR than those with high CRP or WBC alone. Both CRP and WBC were significantly
      associated with risks of IR. CRP might be a more effective biomarker in terms of
      the association with IR.

PMID- 21076978
TI  - Assessment of gait parameters and fatigue in MS patients during inpatient
      rehabilitation: a pilot trial.
AB  - Gait impairment and fatigue are common and disabling problems in multiple
      sclerosis (MS). Characterisation of abnormal gait in MS patients has been done
      mainly using observational studies and simple walking tests providing only
      limited quantitative and no qualitative data, or using intricate and time
      consuming assessment procedures. In addition, the correlation of gait impairments
      with fatigue is largely unknown. The aim of this study was to characterise spatio
      temporal gait parameters by a simple and easy-to-use gait analysis system
      (GAITRite(r)) in MS patients compared with healthy controls, and to analyse
      changes and correlation with fatigue during inpatient rehabilitation. Twenty-four
      MS patients (EDSS <6.5) admitted for inpatient rehabilitation and 19 healthy
      subjects were evaluated using the GAITRite(r) Functional Ambulation System.
      Between-group differences and changes of gait parameters during inpatient
      rehabilitation were analysed, and correlation with fatigue, using the Wurzburg
      Fatigue Inventory for Multiple Sclerosis (WEIMuS), was determined. Compared to
      healthy controls MS patients showed significant impairments in different spatio
      temporal gait parameters, which showed a significant improvement during inpatient
      rehabilitation. Different gait parameters were correlated with fatigue physical
      score, and change of gait parameters was correlated with improvement of fatigue.
      Spatio-temporal gait analysis is helpful to assess specific walking impairments
      in MS patients and subtle changes during rehabilitation. Correlation with fatigue
      may indicate a possible negative impact of fatigue on rehabilitation outcome.

PMID- 21076980
TI  - Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists.
AB  - In this article, we describe the design, synthesis and activity evaluation of
      glycomimetic DC-SIGN antagonists, that use a mannose residue to anchor to the
      protein carbohydrate recognition domain (CRD). The molecules were designed from
      the structure of the known pseudo-mannobioside antagonist 1, by including
      additional hydrophobic groups, which were expected to engage lipophilic areas of
      DC-SIGN CRD. The results demonstrate that the synthesized compounds potently
      inhibit DC-SIGN-mediated adhesion to mannan coated plates. Additionally, in
      silico docking studies were performed to rationalize the results and to suggest
      further optimization.

PMID- 21076982
TI  - Direct analysis of trace elements in crude oils by high-repetition-rate
      femtosecond laser ablation coupled to ICPMS detection.
AB  - IR-femtosecond pulses were used at high repetition rates (up to 10 kHz) to ablate
      viscous crude oils for the determination of trace elements by ICPMS. A special
      internal glass cap was fitted into the ablation cell to minimise oil splashes and
      remove big particles that would be otherwise spread into the cell. Laser ablation
      in static and dynamic conditions (i.e. the laser beam being moved rapidly at the
      surface of the sample) was studied together with some fundamental parameters like
      repetition rate and fluence. Signal sensitivity and stability were found to be
      strongly affected by repetition rate and fluence, though not in linear manner,
      and in some circumstances by the laser beam velocity. Sample transport efficiency
      was found to decrease with increasing repetition rate, probably due to stronger
      particle agglomeration when increasing the density of primary particles. ICPMS
      plasma atomisation/ionisation efficiency was also found to be affected to some
      extent at the highest repetition rates. Moderate repetition rate (1 kHz), high
      fluence (24 J cm(-2)) and fast scanning velocity (100 mm s(-1)) were preferred
      taking into account signal intensity and stability. Sample transport elemental
      fractionation was also evidenced, particularly as regards to carbon due to
      volatilisation of volatile organic species. Matrix effect occurring when
      comparing the ablation of transparent (base oil) and opaque (crude oil) samples
      could not be completely suppressed by the use of IR femtosecond pulses, requiring
      a matrix matching or a standard addition calibration approach. This approach
      provided good accuracy and very low detection limits in the crude oil, in the
      range of ng g(-1).

PMID- 21076979
TI  - Conditional meta-analysis stratifying on detailed HLA genotypes identifies a
      novel type 1 diabetes locus around TCF19 in the MHC.
AB  - The human leukocyte antigen (HLA) class II genes HLA-DRB1, -DQA1 and -DQB1 are
      the strongest genetic factors for type 1 diabetes (T1D). Additional loci in the
      major histocompatibility complex (MHC) are difficult to identify due to the
      region's high gene density and complex linkage disequilibrium (LD). To facilitate
      the association analysis, two novel algorithms were implemented in this study:
      one for phasing the multi-allelic HLA genotypes in trio families, and one for
      partitioning the HLA strata in conditional testing. Screening and replication
      were performed on two large and independent datasets: the Wellcome Trust Case
      Control Consortium (WTCCC) dataset of 2,000 cases and 1,504 controls, and the T1D
      Genetics Consortium (T1DGC) dataset of 2,300 nuclear families. After imputation,
      the two datasets have 1,941 common SNPs in the MHC, of which 22 were successfully
      tested and replicated based on the statistical testing stratifying on the
      detailed DRB1 and DQB1 genotypes. Further conditional tests using the combined
      dataset confirmed eight novel SNP associations around 31.3 Mb on chromosome 6
      (rs3094663, p = 1.66 * 10(-11) and rs2523619, p = 2.77 * 10(-10) conditional on
      the DR/DQ genotypes). A subsequent LD analysis established TCF19, POU5F1, CCHCR1
      and PSORS1C1 as potential causal genes for the observed association.

PMID- 21076981
TI  - Fatal pulmonary oedema following oxytocin administration in a pregnant woman with
      acute myocardial infarction.
AB  - Acute myocardial infarction is a rare event in pregnant patients. Mechanical
      valves are naturally thrombogenic and require careful anticoagulation. Pregnancy
      produces a hypercoagulable situation and necessitates close follow-up in pregnant
      patients with mechanical heart valves. We present a 34-year-old pregnant woman
      who had mitral and aortic valve prosthesis. She developed resistant pulmonary
      oedema in the post-partum period after myocardial infarction. Oxytocin was used
      in this patient to induce midterm labour and prevent post-partum bleeding. Issues
      surrounding management of pulmonary oedema and use of oxytocin therapy during
      pregnancy are discussed. We emphasize the need for awareness of this condition
      and call attention to the risk of pulmonary oedema during labour.

PMID- 21076983
TI  - Integrating the niche and neutral perspectives on community structure and
      dynamics.
AB  - Elucidating the mechanisms underlying the assembly and dynamics of ecological
      communities is a fundamental goal of ecology. Two conceptual approaches have
      emerged in this respect: the niche-assembly view and the neutral perspective. The
      debate as to which approach best explains the biodiversity patterns observed in
      nature is becoming outdated, as ecologists increasingly agree on the existence of
      a niche-neutral continuum of community dynamical behaviors. However, attempts to
      make the continuum idea operational and measurable remain sparse. Here, we
      propose a model-based approach to achieving this. The proposed methodology
      consists of separating out fluctuations in species abundances into niche-mediated
      and stochastic factors, linking the niche configuration to community dynamics
      through competition, and adding demographic stochasticity. This results in a
      comprehensive framework including neutrality and strict niche segregation as
      extreme cases. We develop an index of departure from neutral drift as a surrogate
      for community position on the niche-neutral continuum. We evaluate the
      performance of our modeling approach with simulated data, and subsequently use
      the model to analyze rodent web-trapping data from a real-world system. The model
      fitting is carried out with a Bayesian approach using Markov chain Monte Carlo
      simulation methods.

PMID- 21076984
TI  - Hemolytic uremic syndrome associated with novel influenza A H1N1 infection.

PMID- 21076985
TI  - Hepatocyte growth factor promotes liver regeneration induced by transfusion of
      bone marrow mononuclear cells in a murine acute liver failure model.
AB  - BACKGROUND/PURPOSE: Bone marrow mononuclear cell (BMMC) transplantation has been
      shown to facilitate tissue and organ regeneration and repair. BMMC
      transplantation may be a potential therapy for acute liver failure, and its
      effect might be further improved. Hepatocyte growth factor (HGF) plays an
      important role in liver cell development, and may ameliorate hepatic fibrosis or
      cirrhosis in animal models. We therefore explored a potential synergistic effect
      of the co-application of HGF and BMMCs in liver regeneration following carbon
      tetrachloride (CCl(4))-induced acute hepatic injury. METHODS: We established a
      murine acute liver failure model induced by CCl(4) administration, and studied
      the effect of BMMC transplantation in combination with HGF. We used 4 groups of
      animals, one group was transfused with PKH26-labeled BMMCs (5 * 10(6)) and HGF
      [50 ng/(kg days) * 7 days] (BMMCs + HGF group), one group received BMMCs only,
      one group received HGF only, and one group received saline solution (0.9% NaCl)
      alone. The effects were examined by biochemical measurements of liver enzymes and
      quantitative image analysis for PKH26 labeling, and by determining proliferating
      cell nuclear antigen (PCNA) and albumin expression 4 weeks after the BMMC
      transplantation. RESULTS: PKH26-labeled BMMCs were detected in transplanted mouse
      livers, most of which expressed PCNA. PCNA and albumin expressions were increased
      significantly in the BMMCs + HGF group compared with the expressions of these
      parameters in the other 3 groups. Liver function, reflected by serum
      aminotransferase activity, was also improved in the BMMCs + HGF group relative to
      that in the other groups. CONCLUSIONS: Data from the present study appear to
      suggest that BMMC transplantation combined with HGF administration exhibits a
      synergistic beneficial effect on improving both functional and histological liver
      recovery in a mouse model of acute liver failure.

PMID- 21076986
TI  - Pancreaticoduodenectomies with a duct-to-mucosa pancreaticojejunostomy
      anastomosis with and without a stenting tube showed no differences in long-term
      follow-up.
AB  - BACKGROUND/PURPOSE: The aim of this study was to evaluate the long-term
      complications of pancreaticoduodenectomy with a duct-to-mucosa
      pancreaticojejunostomy anastomosis without a stenting tube. METHODS: Patients
      were followed for at least 3 years after pancreaticoduodenectomy. They were
      classified into two groups: duct-to-mucosa pancreaticojejunostomy anastomosis
      with a stenting tube (group A: 24) and without a stenting tube (group B: 21).
      Outcomes, including complications and dilatation of the pancreatic duct, were
      reported retrospectively. RESULTS: The following complication rates were found
      for group A: morbidity 29.1%, cholangitis 12.5%, nonalcoholic steatohepatitis
      4.2%, liver abscess 4.2%, intrahepatic stones 4.2%, abnormal glucose tolerance
      (progression of diabetes) 20.8%, and dilatation of the pancreatic duct 20.8%. In
      group B, the rates for morbidity (14.3%) and abnormal glucose tolerance (19%),
      and dilatation of the pancreatic duct (4.8%) were lower than those in group A,
      but all results lacked statistical significance. CONCLUSIONS:
      Pancreaticoduodenectomy with a duct-to-mucosa anastomosis of
      pancreaticojejunostomy with or without a stenting tube showed no difference in
      long-term follow-up.

PMID- 21076987
TI  - Cerebrospinal fluid under non-steady state condition caused by plasmapheresis.
AB  - We present an unusual constellation of the CSF/serum biomarkers of Guillain-Barre
      syndrome caused by unsteady-state condition of protein diffusion induced by
      plasmapheresis. Low blood concentrations of immunoglobulins were accompanied by
      their normal concentrations in the CSF, and hence the corresponding CSF/serum
      quotients seemed 'increased' suggesting intrathecal humoral response. This was in
      contrast to the results of isoelectrofocusing showing identical IgG bands pattern
      in the CSF and serum. Control lumbar puncture performed 6 weeks after the
      cessation of plasmapheresis, revealed normalization of the immunoglobulins'
      quotients. It must be stressed that the results of the CSF/serum analysis
      performed under non-steady state condition may be easily misinterpreted, and only
      considering the whole pattern of the CSF/serum biomarkers can assure correct
      interpretation of the results.

PMID- 21076988
TI  - Postsynaptic nigrostriatal dopamine receptors and their role in movement
      regulation.
AB  - The article presents the hypothesis that nigrostriatal dopamine may regulate
      movement by modulation of tone and contraction in skeletal muscles through a
      concentration-dependent influence on the postsynaptic D1 and D2 receptors on the
      follow manner: nigrostriatal axons innervate both receptor types within the
      striatal locus somatotopically responsible for motor control in
      agonist/antagonist muscle pair around a given joint. D1 receptors interact with
      lower and D2 receptors with higher dopamine concentrations. Synaptic dopamine
      concentration increases immediately before movement starts. We hypothesize that
      increasing dopamine concentrations stimulate first the D1 receptors and reduce
      muscle tone in the antagonist muscle and than stimulate D2 receptors and induce
      contraction in the agonist muscle. The preceded muscle tone reduction in the
      antagonist muscle eases the efficient contraction of the agonist. Our hypothesis
      is applicable for an explanation of physiological movement regulation, different
      forms of movement pathology and therapeutic drug effects. Further, this
      hypothesis provides a theoretical basis for experimental investigation of
      dopaminergic motor control and development of new strategies for treatment of
      movement disorders.

PMID- 21076989
TI  - CD28 superagonist-induced regulatory T cell expansion ameliorates
      mesangioproliferative glomerulonephritis in rats.
AB  - BACKGROUND: Naturally occurring regulatory T cells (Treg) are essential for the
      prevention of autoimmunity and overshooting immune responses to pathogens;
      however, the involvement of Treg in mesangioproliferative glomerulonephritis, a
      major cause of chronic kidney disease, remains unclear. Superagonistic CD28
      specific monoclonal antibodies (CD28SA) are highly effective activators of Treg
      in rats. METHOD: To confirm our hypothesis that CD28SA reduces the severity of
      experimental glomerulonephritis, anti-Thy1 nephritis model rats were treated with
      CD28SA or saline. RESULTS: CD28SA significantly suppressed the increase in
      proteinuria and serum creatinine levels. CD28SA-treated nephritic rats exhibited
      an increase in the infiltration of Treg in the glomeruli accompanied by
      infiltration of CD163-positive macrophages ("alternatively activated"
      macrophages). In addition, CD28SA significantly induced interleukin-10 mRNA
      expression in glomeruli, thereby ameliorating mesangial cell proliferation and
      extracellular matrix expansion. CONCLUSION: We established a new therapeutic
      approach to suppressing progressive glomerulonephritis. The therapeutic value of
      this approach warrants further attention and preclinical studies.

PMID- 21076991
TI  - A historical perspective on the evolution of resting-state functional
      connectivity with MRI.
AB  - In this review article, I discuss initial and recent studies of the assessment of
      functional connectivity in the human brain using low-frequency BOLD fluctuations
      in the resting state. By putting the studies in their historical context, the
      goal is to give the reader an appreciation of the evolution of the field and the
      pivotal events and studies that have led to the widespread acceptance of the
      method as a neuroscience tool for investigating functional connectivity in the
      human brain.

PMID- 21076992
TI  - Evaluation of foam cell formation in cultured macrophages: an improved method
      with Oil Red O staining and DiI-oxLDL uptake.
AB  - Macrophage-derived foam cell formation elicited by oxidized low-density
      lipoprotein (oxLDL) is the hallmark of early atherogenesis. Detection of foam
      cell formation is conventionally practiced by Oil Red O (ORO) staining of lipid
      laden macrophages. Other methods include 1,1'-dioctadecyl-3,3,3'3'-tetra
      methylindocyanide percholorate (DiI)-labeled oxLDL (DiI-oxLDL) uptake and Nile
      Red staining. The purpose of the present study is to report an optimized method
      for assessing foam cell formation in cultured macrophages by ORO staining and DiI
      oxLDL uptake. After incubation with oxLDL (50 MUg/ml) for 24 h, the macrophages
      were fixed, stained with ORO for just 1 min, pronounced lipid droplets were
      clearly observed in more than 90% of the macrophages. To test the in vivo
      applicability of this method, lesions (or foam cells) of cryosections of aortic
      sinus or primary mouse peritoneal macrophages from ApoE deficient mice fed a high
      cholesterol diet were successfully stained. In another set of experiments,
      treatment of macrophages with DiI-oxLDL (10 MUg/ml) for 4 h resulted in
      significant increase in oxLDL uptake in macrophages as demonstrated by confocol
      microscopy and flow cytometry. We conclude that the optimized ORO staining and
      fluorescent labeled oxLDL uptake techniques are very useful for assessing
      intracellular lipid accumulation in macrophages that are simpler and more rapid
      than currently used methods.

PMID- 21076990
TI  - Altered expression of securin (Pttg1) and serpina3n in the auditory system of
      hearing-impaired Tff3-deficient mice.
AB  - INTRODUCTION: Tff3 peptide exerts important functions in cytoprotection and
      restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence
      in the rodent inner ear and involvement in the hearing process was demonstrated
      recently. However, its role in the auditory system still remains elusive. Our
      previous results showed a deterioration of hearing with age in Tff3-deficient
      animals. RESULTS: Present detailed analysis of auditory brain stem response (ABR)
      measurements and immunohistochemical study of selected functional proteins
      indicated a normal function and phenotype of the cochlea in Tff3 mutants.
      However, a microarray-based screening of tissue derived from the auditory central
      nervous system revealed an alteration of securin (Pttg1) and serpina3n expression
      between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR,
      immunostaining and western blots. CONCLUSIONS: We found highly down-regulated
      Pttg1 and up-regulated serpina3n expression as a consequence of genetically
      deleting Tff3 in mice, indicating a potential role of these factors during the
      development of presbyacusis.

PMID- 21076994
TI  - Bariatric surgery is associated with reduced depressive symptoms and better
      sexual function in obese female patients: a one-year follow-up study.
AB  - Bariatric surgery is an effective treatment for obesity; few studies, however,
      have investigated its impact on patients' sexuality. We aimed to determine
      bariatric surgery's effect on female patients' body mass index (BMI), anxiety and
      depressive symptoms, and sexual function and delineate predictors of treatment
      outcomes. Fifty-nine obese female bariatric candidates were administered the
      Hospital Anxiety and Depression Scale and the Female Sexual Function Index 1 week
      before surgery (T1) and 1 year after (T2). Statistical analysis revealed
      significant reductions in BMI (p < 0.001), depression (p < 0.001), and sexual
      pain levels (p = 0.014) and significant improvements in sexual desire (p =
      0.005), arousal (p = 0.001), lubrication (p = 0.003), satisfaction (p = 0.012),
      and total sexual function (p = 0.003) postoperatively. Postoperative total sexual
      function was independently predicted by baseline sexual function and low baseline
      BMI. Bariatric surgery is an effective way to reduce weight, manage depression,
      and improve sexual function in female obese patients.

PMID- 21076993
TI  - Influence of gender on continuous positive airway pressure requirements in
      patients with obstructive sleep apnea syndrome.
AB  - INTRODUCTION: Gender differences have been noted in key aspects of upper airway
      physiology and pathophysiology of obstructive sleep apnea (OSA). We postulate
      that these will lead to disparities in pharyngeal collapsibility and,
      consequently, positive airway pressure requirements of patients with OSA.
      METHODS: A retrospective review of 95 adult patients (56 women, 39 men) with OSA
      was done. Patients who underwent continuous positive airway pressure (CPAP)
      titration were included in the study. RESULTS: The study groups were similar with
      regard to the severity of OSA (median apnea-hypopnea index of 34 in men and 24 in
      women, p = 0.13). The men were older and less obese than the women (mean age of
      46 and 41 years, p = 0.03, BMI of 42 and 49 kg/m(2), p < 0.001, in men and women,
      respectively); Epworth score was similar in the two groups (12 vs.11, p = 0.91).
      CPAP requirement was higher in men than in women (12.7 vs. 10.2, p < 0.0001). The
      effect of gender on CPAP requirement was found to be significant even when
      confounding variables were accounted for using linear regression. CONCLUSION: Men
      with OSA are more likely to require higher levels of CPAP support than women. The
      effect of gender on CPAP requirement persisted even after correcting for the
      severity of OSA.

PMID- 21076995
TI  - Phase II study of ABVd therapy for newly diagnosed clinical stage II-IV Hodgkin
      lymphoma: Japan Clinical Oncology Group study (JCOG 9305).
AB  - Although ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) therapy has
      been regarded as a standard of care for advanced-stage Hodgkin lymphoma (HL)
      since 1992, there has been no prospective data of ABVD therapy in Japan. To
      investigate the efficacy and safety of ABVd therapy with the lower dose of
      dacarbazine (250 mg/m(2)) in patients with newly diagnosed stage II-IV HL,
      Lymphoma Study Group of Japan Clinical Oncology Group conducted a phase II study.
      The primary endpoints were complete response rate (%CR) and progression-free
      survival (PFS). A total of 128 patients with age less than 70 years were enrolled
      and received 6-8 cycles of ABVd followed by radiation to initial bulky mass. The
      %CR in 118 eligible patients was 81.4% [95% confidence interval (CI) 73.1-87.9%].
      Major toxicity was grade 4 neutropenia (45.3%). Grade 3 nausea/vomiting was the
      most frequent non-hematological toxicity (10.9%). Transient grade 4 constipation,
      infection (abscess), hypoxemia and hyperbilirubinemia were observed in 4
      patients. No treatment-related death was observed. PFS and overall survival at 5
      years were 78.4% (95% CI 70.9-85.9%) and 91.3% (95% CI 86.1-96.5%), respectively.
      In conclusion, ABVd is effective in Japanese patients with stage II-IV HL with
      acceptable toxicities (UMIN-CTR Number: C000000092).

PMID- 21076996
TI  - Periaqueductal grey stimulation induced panic-like behaviour is accompanied by
      deactivation of the deep cerebellar nuclei.
AB  - Until recently, the cerebellum was primarily considered to be a structure
      involved in motor behaviour. New anatomical and clinical evidence has shown that
      the cerebellum is also involved in higher cognitive functions and non-motor
      behavioural changes. Functional imaging in patients with anxiety disorders and in
      cholecystokinin tetrapeptide-induced panic-attacks shows activation changes in
      the cerebellum. Deep brain stimulation of the dorsolateral periaqueductal grey
      (dlPAG) and the ventromedial hypothalamus (VMH) in rats has been shown to induce
      escape behaviour, which mimics a panic attack in humans. We used this animal
      model to study the neuronal activation in the deep cerebellar nuclei (DCbN) using
      c-Fos immunohistochemistry. c-Fos expression in the DCbN decreased significantly
      after inducing escape behaviour by stimulation of the dlPAG and the VMH,
      indicating that the DCbN were deactivated. This study demonstrates that the DCbN
      are directly or indirectly involved in panic attacks. We suggest that the
      cerebellum plays a role in the selection of relevant information, and that
      deactivation of the cerebellar nuclei is required to allow inappropriate
      behaviour to occur, such as panic attacks.

PMID- 21076997
TI  - Impact of air pollution control measures and weather conditions on asthma during
      the 2008 Summer Olympic Games in Beijing.
AB  - The alternative transportation strategy implemented during the 2008 Summer
      Olympic Games in Beijing provided an opportunity to study the impact of the
      control measures and weather conditions on air quality and asthma morbidity. An
      ecological study compared the 41 days of the Olympic Games (8 August-17 September
      2008) to a baseline period (1-30 June). Also, in order to emphasize the impact of
      weather conditions on air quality, a pollution linking meteorological index
      (Plam) was introduced to represent the air pollution meteorological condition.
      Our study showed that the average number of outpatient visits for asthma was 12.5
      per day at baseline and 7.3 per day during the Olympics-a 41.6% overall decrease.
      Compared with the baseline, the Games were associated with a significant
      reduction in asthma visits (RR 0.58, 95%CI: 0.52-0.65). At 16.5 visits per day,
      asthma visits were also significantly higher, during the pre-Olympic period (RR
      1.32, 95% CI: 1.15-1.52). The study also showed that the RR of asthma events on a
      given day, as well as the average daily peak ozone concentration during the
      preceding 48-72 h, increased at cumulative ozone concentrations of 70 to 100 ppb
      and 100 ppb or more compared with ozone concentrations of less than 70 ppb (P <
      0.05). We concluded that along with "good" weather conditions, efforts to reduce
      traffic congestion in Beijing during the Olympic Games were associated with a
      prolonged reduction in air pollution and significantly lower rates of adult
      asthma events. These data provide support for efforts to reduce air pollution and
      improve health via reductions in motor vehicle traffic.

PMID- 21076998
TI  - Complete correction of anemia by erythropoiesis-stimulating agents is associated
      with insulin resistance in hemodialysis patients.
AB  - Insulin resistance and anemia secondary to erythropoietin deficiency characterize
      patients with end-stage kidney disease. In a cross-sectional analysis, we
      examined the relationship between erythropoietin-mediated correction of anemia
      and insulin sensitivity in nondiabetic hemodialysis patients. Insulin sensitivity
      (euglycemic-hyperinsulinemic clamp) and endogenous glucose production (primed
      continuous infusion of [6,6-(2)H(2)]glucose) were determined in two groups of
      patients with normal hemoglobin (n:8; mean hemoglobin: 14.0 +/- 0.3 g/dl) or with
      mild anemia (n:10; mean hemoglobin: 12.1 +/- 0.9 g/dl). The patients with normal
      hemoglobin were receiving higher (P < 0.05) erythropoietin doses than those with
      mild anemia (171 +/- 73 and 91 +/- 39 U kg(-1) wk(-1), respectively). The two
      groups were matched for all other potential determinants of insulin resistance.
      Endogenous glucose production was similar in the two groups of patients in the
      postabsorptive state and was completely suppressed by insulin infusion. During
      the hyperinsulinemic clamp, the rate of glucose infusion to maintain euglycemia
      was significantly lower (P < 0.01) in the patients with normal hemoglobin levels
      [166 +/- 31 mg (m(2))(-1) min(-1)] than in those with mild anemia [251 +/- 49 mg
      (m(2))(-1) min(-1)] and in a group of matched controls [275 +/- 68 mg (m(2))(-1)
      min(-1)]. In pooled patients, individual values of hemoglobin concentrations
      inversely correlated with the rates of insulin-mediated glucose infusion, both as
      absolute values (r = -0.58; P < 0.05) and as values normalized by steady-state
      plasma insulin concentration (r = -0.74; P < 0.001). In conclusion, this
      exploratory study indicates that complete correction of anemia by erythropoietin
      treatment in patients with end-stage kidney disease on hemodialysis is associated
      with impaired insulin sensitivity.

PMID- 21076999
TI  - Total mercury loadings in sediment from gold mining and conservation areas in
      Guyana.
AB  - The Low Carbon Development Strategy proposed in June 2009 by the government of
      Guyana in response to the Reducing Emissions from Deforestation and Forest
      Degradation in Developing Countries program has triggered evaluation of forest
      related activities, thereby acting as a catalyst for improvements in Guyana's
      small- to medium-scale gold mining industry. This has also shed light on areas
      committed to conservation, something that has also been handled by Non
      Governmental Organizations. This paper compares water quality and mercury
      concentrations in sediment from four main areas in Guyana, two that are heavily
      mined for gold using mercury amalgamation methods (Arakaka and Mahdia) and two
      that are considered conservation areas (Iwokrama and Konashen). Fifty-three
      sediment and soil mercury loadings ranged from 29 to 1,200 ng/g and averaged 215
      +/- 187 ng/g for all sites with similar averages in conservation and mining
      areas. Sediment loadings are within the range seen in French Guiana and Suriname,
      but conservation area samples had higher loadings than the corresponding
      uncontaminated baselines. Type of ore and location in the mining process seemed
      to influence mercury loadings. Mercury sediment loadings were slightly positively
      correlated with pH (correlation coefficient = 0.2; p value < 0.001) whereas no
      significant correlations were found with dissolved oxygen or turbidity.

PMID- 21077000
TI  - Diagnostic value of elastosonographically determined strain index in the
      differential diagnosis of benign and malignant thyroid nodules.
AB  - Elastosonography (ES) is a newly developed method that is used for the
      differential diagnosis of benign and malignant thyroid nodules. In different
      studies, ES scoring has been compared with histopathological findings, and
      sensitivity and specificity of the scoring were calculated. In this study, it
      determines the strain index (SI) as well as the ES to score thyroid nodules, and
      establishes the role for these parameters in the differential diagnosis of
      thyroid nodules using histopathological analysis as a reference standard. Real
      time ES in transverse axis (TA) and longitudinal axis (LA) was performed in 391
      nodules of 292 patients. ES scoring was made for all the nodules. SI in TA and LA
      was calculated for four times in each nodule and mean values were determined. The
      results were compared with final histopathological diagnoses. In
      histopathological examinations, 125 (31.97%) of 391 nodules were malignant and
      266 (68.03%) were benign. Of these histopathologically benign nodules, 189
      (%71.05) were also probably benign according to elastosonographic scoring (scores
      of 1, 2, or 3), while 77 (28.95%) were probably malignant (scores of 4 or 5).
      Among 125 histopathologically malignant nodules, 52 (41.60%) were probably benign
      and 73 (58.40%) were probably malignant according to elastosonographic scoring.
      There was a significant relation between scoring and histopathological findings
      (chi(2) = 36.513; P < 0.001). Accordingly, sensitivity and specificity of ES
      scoring were 58.4 and 71.0%, respectively. ROC analysis value obtained for strain
      ratios in LA (AUC: 75.5%; P < 0.001) had a higher significance compared to ROC
      analysis value obtained for strain ratios in TA (AUC: 66.0%). Thus, ROC analysis
      evaluation was applied only for SI in LA. The optimal SI cut-off value in LA for
      all the nodules was found to be 16.709 (sensitivity: 73.4%, specificity: 70.0%)
      (AUC: 75.4 +/- 0.03%; 70.2-80.5%). SI cut-off value corresponding to 90%
      sensitivity in this axis was 4.516 (specificity: 35.7%). Sensitivity and
      specificity of SI values that were determined according to morphological features
      of nodules in gray-scale ultrasonography were higher. For hypoechoic nodules with
      microcalcifications and without a halo, SI cut-off value, sensitivity, and
      specificity were 17.020, 84.3, and 81.1%, respectively. Our study is the first
      clinical-wide series study that measured, used, and compared the ES scoring and
      SI cut-off values for the differential diagnosis of benign and malignant thyroid
      nodules. This study indicates that measurement of SI with ES as a noninvasive
      procedure may be used as an adjunctive method to the conventional methods for the
      differential diagnosis of thyroid nodules.

PMID- 21077001
TI  - Effect of post-match cold-water immersion on subsequent match running performance
      in junior soccer players during tournament play.
AB  - In this study, we investigated the effects of two hydrotherapy interventions on
      match running performance and perceptual measures of fatigue and recovery during
      a 4-day soccer tournament. Twenty male junior soccer players were assigned to one
      of two treatment groups and undertook either cold-water immersion (5 * 1 min at
      10  degrees C) or thermoneutral water immersion (5 * 1 min at 34  degrees C)
      after each match. High-intensity running distance (>15 km . h-1) and total
      distance covered, time spent in low (<80% maximum heart rate), moderate (80-90%
      maximum heart rate), and high (>90% maximum heart rate) heart rate zones, and
      rating of perceived exertion (RPE) were recorded for each match. Perceptions of
      general fatigue and leg soreness were recorded approximately 22 h after each
      match. There were decreases in both groups across the 4-day tournament for high
      intensity running distance (P = 0.006, Cohen's d = 0.63), total distance run (P <
      0.001, d = 0.90), time in high heart rate zone (P = 0.003, d = 0.90), and match
      RPE (P = 0.012, d = 0.52). Cold-water immersion was more effective than
      thermoneutral immersion for reducing the perception of leg soreness (P = 0.004, d
      = -0.92) and general fatigue (P = 0.007, d = -0.91), ameliorating the decrement
      in total distance run (P = 0.001, d = 0.55), and maintaining time in the moderate
      heart rate zone (P = 0.01, d = 1.06). In conclusion, cold-water immersion
      mediates the perceptions of fatigue and recovery and enhances the restoration of
      some match-related performance measures during a 4-day tournament.

PMID- 21077002
TI  - Participation-related relative age effects in Masters swimming: a 6-year
      retrospective longitudinal analysis.
AB  - Medic and colleagues (Medic, Starkes, & Young, 2007) found that relatively
      younger cohorts of Masters athletes had higher participation rates and achieved
      higher performances compared with a relatively older cohort. Considering that
      Medic and colleagues' (2007) study was cross-sectional in nature, the purpose of
      this investigation was to employ a retrospective longitudinal study design to
      examine the participation rates of Masters swimmers as a function of an
      individual's constituent year within any 5-year age category over a period of 6
      years. Using archived data from the 2003 to 2009 US Masters Short Course National
      Championships, swimmers' attendance was followed for a period of six consecutive
      years. Results indicated that a participation-related relative age effect was
      observed among swimmers who, over a period of 6 years, competed in either at
      least one championship (N = 2596; Cochran's Q4 = 64.16, r(s) = -0.92, both P <
      0.0001) or at least three championships (N = 441; Cochran's Q4 = 47.51, r(s) = 
      0.91, both P < 0.0001). Overall, effect size analyses indicated that the odds of
      a Masters swimmer participating in the championship during the first constituent
      year of any 5-year age category was more than two times greater than the odds of
      that athlete participating during the fifth constituent year.

PMID- 21077003
TI  - Exploring the relationship between hope and burnout in competitive sport.
AB  - Researchers have postulated that hope may be an important factor associated with
      burnout. Consistent with hope theory contentions, low-hope individuals may be
      susceptible to burnout because they are prone to experience goal blockage,
      frustration, and negative affect, all of which likely increase the risk of
      burnout. We examined the relationship between hope and athlete burnout among 178
      competitive athletes (63 females and 115 males) aged 15-20 years. Hope was
      significantly and negatively correlated with all three burnout subscales:
      emotional/physical exhaustion, a reduced sense of accomplishment, and sport
      devaluation. Moreover, results of a multivariate analysis of variance showed that
      low-hope athletes scored significantly higher than medium- and high-hope athletes
      on all three burnout dimensions. Finally, results revealed that agency thinking
      was a significant predictor of all burnout dimensions. Frustration over unmet
      goals and a perceived lack of agency, a characteristic of low-hope athletes,
      might pose a risk factor in athlete burnout, whereas being able to maintain hope
      appears to be associated with health and well-being.

PMID- 21077004
TI  - Are declines in physical performance associated with a reduction in skill-related
      performance during professional soccer match-play?
AB  - The aim of this study was to determine whether declines in physical performance
      in a professional soccer team during match-play were associated with reductions
      in skill-related performance. Computerized tracking of performance in midfield
      players (n = 11) showed that total distance and distance covered in high-speed
      running (>14.4 km . h-1) were greater in the first versus second half of games
      (both P < 0.001) and in the first versus the final 15 min of play (P < 0.05).
      Analysis of high-speed running across 5-min periods showed that more distance was
      covered in the first versus the final game period, and in the peak period of
      activity compared with the following period and game mean for other periods (all
      P < 0.05). Analysis of skill-related measures revealed no significant decline
      between halves, across 15-min intervals or in the 5-min period following that of
      peak high-speed activity compared with the game mean for other 5-min periods. In
      contrast, frequencies of passing, ball possessions, and duels were greater in the
      first 5-min than in the final 5-min period (P < 0.05). Neither physical nor skill
      related performance was affected across three consecutive games within a period
      of <=7 days. The results suggest that the players were generally able to maintain
      skill-related performance throughout games and when competing in successive
      matches within a short time.

PMID- 21077005
TI  - Time-motion, heart rate, perceptual and motor behaviour demands in small-sides
      soccer games: effects of pitch size.
AB  - The aim of this study was to examine physical, physiological, and motor responses
      and perceived exertion during different soccer drills. In small-sided games, the
      individual playing area (~ 275 m2, ~ 175 m2, and ~ 75 m2) was varied while the
      number of players per team was kept constant: 5 vs. 5 plus goalkeepers.
      Participants were ten male youth soccer players. Each session comprised three
      small-sided game formats, which lasted 8 min each with a 5-min passive rest
      period between them. A range of variables was recorded and analysed for the three
      drills performed over three training sessions: (a) physiological, measured using
      Polar Team devices; (b) physical, using GPS SPI elite devices; (c) perceived
      exertion, rated using the CR-10 scale; and (d) motor response, evaluated using an
      observational tool that was specially designed for this study. Significant
      differences were observed for most of the variables studied. When the individual
      playing area was larger, the effective playing time, the physical (total distance
      covered; distances covered in low-intensity running, medium-intensity running,
      and high-intensity running; distance covered per minute; maximum speed; work-to
      rest ratio; sprint frequency) and physiological workload (percent maximum heart
      rate; percent mean heart rate; time spent above 90% maximum heart rate), and the
      rating of perceived exertion were all higher, while certain motor behaviours were
      observed less frequently (interception, control and dribble, control and shoot,
      clearance, and putting the ball in play). The results show that the size of the
      pitch should be taken into account when planning training drills, as it
      influences the intensity of the task and the motor response of players.

PMID- 21077006
TI  - Supported and unsupported breast displacement in three dimensions across
      treadmill activity levels.
AB  - Appropriate sports bras are crucial to limit potential breast pain and ptosis. In
      an attempt to optimize breast support during exercise, manufacturers now produce
      activity level-specific sports bras. However, until breast movement across
      activity levels is understood, the criterion for such apparel is unknown.
      Therefore, the aim of this study was to quantify multi-planar breast displacement
      across treadmill activity levels and breast support conditions. Twenty-one D cup
      participants had markers attached to their nipples and trunk to calculate
      relative 3D breast displacement. Supported and unsupported mediolateral,
      anterioposterior, vertical, and resultant breast displacement was assessed during
      treadmill walking up to maximum running. Unsupported resultant breast
      displacement increased from 4.2 +/- 1.0 cm during walking to 15.2 +/- 4.2 cm
      during running. There was no change in breast displacement amplitude or direction
      as running speed increased above 10 km . h-1, with vertical breast displacement
      then accounting for ~50% of overall displacement. While breast support was
      effective in reducing the amplitude of breast displacement during walking and
      running, the direction was unaffected. In conclusion, instead of activity level
      specific breast support, future research should identify multi-planar breast
      kinematics during various sporting modalities. This might lead to production of a
      sports-specific bra to reduce the negative consequences of breast movement.

PMID- 21077007
TI  - Complementary lateralisation in the exploratory and predatory behaviour of the
      common wall lizard (Podarcis muralis).
AB  - Several ectotherms show lateralisation, particularly visual lateralisation. Such
      brain specialisation has an ancient origin and is still present in living
      vertebrates. One important advantage is the possibility for lateralised animals
      to carry out two tasks at the same time, without altering the efficiency of
      either one. Recent studies on the common wall lizard (Podarcis muralis) found
      right eye/left hemisphere bias for attention to the cues of prey, and left
      eye/right hemisphere bias for controlling antipredatory and exploratory
      behaviours. However, these studies were independent of each other and therefore
      were not empirical demonstrations that the directions of visual lateralisation
      found in this species are present in the same individual, allowing the
      simultaneous performance of dual tasks. In our study the same Podarcis muralis
      individuals carried out one exploratory and one predatory test each. We allowed
      each lizard to move freely in a circular arena, with opaque walls, with either
      nothing or mealworm larvae in the centre. In the first case the test was an
      exploratory test, while in the second case it was a predatory one. The results
      indicated that lizards preferentially used the left eye to observe the
      environment--i.e., during exploration--and just tended to use the right eye
      during predation. Hence we conclude that in the Podarcis muralis lizard
      lateralisation is expressed in the same individual in opposite directions, in
      accordance with previous observations.

PMID- 21077009
TI  - Psychophysiological effects of emotional display rules and the moderating role of
      trait anger in a simulated call center.
AB  - In customer interactions, emotional display rules typically prescribe service
      providers to suppress negative emotions and display positive ones. This study
      investigated the causal impact of these emotional display rules on physiological
      indicators of workers' stress and performance. Additionally, the moderating
      influence of personality was examined by analyzing the impact of trait anger. In
      a simulated call center, 82 females were confronted with a complaining customer
      and instructed to react either authentically and show their true emotions or to
      "serve with a smile" and hide negative emotions. Increases in diastolic blood
      pressure and heart rates were higher in the smile condition, while verbal fluency
      was lower. Trait anger moderated the effects on diastolic blood pressure and
      observer ratings' of participants' professional competence, suggesting more
      negative effects for high trait anger individuals. Findings imply that emotional
      display rules may increase call center employees' strain and that considering
      employees' personality may be crucial for precluding health and performance
      impairments among call center workers.

PMID- 21077008
TI  - Impaired goal-directed behavioural control in human impulsivity.
AB  - Two dissociable learning processes underlie instrumental behaviour. Whereas goal
      directed behaviour is controlled by knowledge of the consequences, habitual
      behaviour is elicited directly by antecedent Pavlovian stimuli without knowledge
      of the consequences. Predominance of habitual control is thought to underlie
      psychopathological conditions associated with corticostriatal abnormalities, such
      as impulsivity and drug dependence. To explore this claim, smokers were assessed
      for nicotine dependence, impulsivity, and capacity for goal-directed control over
      instrumental performance in an outcome devaluation procedure. Reduced goal
      directed control was selectively associated with the Motor Impulsivity factor of
      Barrett's Impulsivity Scale (BIS), which reflects propensity for action without
      thought. These data support the claim that human impulsivity is marked by
      impaired use of causal knowledge to make adaptive decisions. The predominance of
      habit learning may play a role in psychopathological conditions that are
      associated with trait impulsivity.

PMID- 21077010
TI  - The impact of socio-cultural context on young people's condom use: evidence from
      two Pacific Island countries.
AB  - Young people are a key group for HIV prevention in the Pacific region where
      levels of STIs are high and condom use is low. During 2008, 62 in-depth
      interviews were conducted with people aged between 18 and 25 years in Tonga and
      Vanuatu. The research was aimed at understanding factors impacting on young
      peoples' condom use in two Pacific Island nations. The data show a marked
      disjuncture between attitudes and practice with regard to condoms. This paper
      discusses factors underpinning that inconsistency and directs attention to the
      effect of social and cultural influences on young people's condom use. The
      authors conclude that individual-level approaches to improving rates of condom
      use will be inadequate unless they are informed by an understanding of the role
      of identity, culture and tradition in young peoples' decisions around condom use.
      The findings also underline the need for country-specific approaches to condom
      promotion efforts in the Pacific.

PMID- 21077011
TI  - Entangled chemosensory emotion and identity: familiarity enhances detection of
      chemosensorily encoded emotion.
AB  - Biologically significant, natural human body odors covey emotion and identity-
      two qualities shown to build on dissociated modules in face and voice
      perceptions. To what extent such segregation applies to chemosensory processing
      of body odors has hardly been studied. The current study probes this issue by
      recruiting heterosexual couples, who are genetically independent yet sexually and
      emotionally engaged to one another, as both odor donors and odor judges, and
      comparing their sensitivities to the chemosensory emotional cues from their
      partner vs. those from opposite-sex strangers. We demonstrate that familiarity
      subconsciously sharpens one's sensitivity to chemosensory emotional cues, which
      increases as a function of the time couples have spent together. Nevertheless,
      the specific chemosensory identity and emotional content remain undelineated and
      inaccessible to verbal awareness. Our findings reveal a different pattern from
      those of face and voice perceptions and provide insights into the mechanisms and
      interplays of chemosensory emotion and identity processings.

PMID- 21077012
TI  - [What is epidemiology?].

PMID- 21077013
TI  - [On the subject of neuro-ophthalmology: All about the pupil].

PMID- 21077014
TI  - [The eye of the inner clock - pupil research in a new light].
AB  - BACKGROUND: Pupillary research has received a new impetus since the discovery of
      the melanopsin containing ganglion cell subpopulation ipRGC (intrinsically
      photosensitive retinal ganglion cells). These specific ganglion cells have a
      maximum spectral sensitivity at 480 nm and affect predominantly the day-night
      cycle (inner clock) and the pupil reaction. They control above all the adjustment
      of the pupil width during continuous lighting, as well as during particularly
      bright and above all short wavelength light. Our results from blind patients with
      retinitis pigmentosa also showed clear pupil light reactions when examined with
      standard pupillographic equipment (CIP, AMTech, Dossenheim) with a yellow
      stimulus. These results are difficult to explain with the previous hypotheses. Up
      till now, there have been only few investigations in groups of patients with
      ophthalmological diseases. These studies indicate that with modified
      pupillographic stimuli, a clear distinction between lesions of the outer and
      inner retina is possible. METHODS: It is of interest for future applied pupillary
      research to ascertain how the pupillary light reaction alters with the
      wavelength, duration and intensity of the light stimulus. For such studies it is
      necessary not only to use well-defined spectral stimuli but also to develop
      special recording techniques and methods of analysis. CONCLUSIONS: It is to be
      expected that the results of such research will have consequences not only for
      the differential diagnosis of pathologies of the outer and inner retina, but also
      on the functional testing of retinal implants. This article gives an overview of
      the current state of knowledge.

PMID- 21077015
TI  - [Pupillary disorders - diagnosis, diseases, consequences].
AB  - Examination of the pupil offers an objective evaluation of visual function as
      well as the vegetative pathways to the eye. Essential information is gathered
      within a short time. This makes pupillary inspection a valuable part of the
      routine ophthalmological, neurological and general medical examinations. Due to
      the proximity of pupillary pathways to various anatomic structures, pupillary
      dysfunction can be caused by a variety of disorders, some of which may be life
      threatening. The ophthalmologist plays a key role in detecting pupillary
      disorders and in directing further investigations. Therefore, one should have a
      good knowledge of the diagnostic significance of pupillary function and
      dysfunction.

PMID- 21077016
TI  - [Colour comparison tests in unilateral optic neuropathies].
AB  - AIM OF THE STUDY: Colour comparison tests are a subjective supplement to the
      swinging flashlight test. We have investigated the specificity and sensitivity,
      compared 3 exactly defined different colours (red, green, blue), and looked for
      age relationships. METHOD: 101 patient with various unilateral optic neuropathies
      were compared to 103 age-correlated healthy controls in randomised order by
      letting the patient evaluate red, green and blue colour charts of 5.5 cm
      diameter. RESULTS: The area under the receiver operator characteristics curve was
      0.804 for red, 0.821 for green and 0.789 for blue, and for any of the 3 colours
      0.835 (at least one colour was seen differently). Best results were obtained when
      even small differences in colour perception were considered as pathological. 29
      healthy controls perceived colours differently in both eyes, 24 of those being
      older than 50 years. The specificity decreased with age, was significant for
      green and red, not for blue. DISCUSSION: There were no significant differences
      between the 3 colours in all age groups. Evaluation of more than one colour does
      not increase the sensitivity significantly. Even small differences have to be
      considered as pathological to obtain the highest possible sensitivity. Test
      specifity decreases with age.

PMID- 21077017
TI  - [Miller-Fisher syndrome and the spectrum of oculomotor palsies with anti-GQ1b
      antibodies].
AB  - The author reports his experience with his own case of Miller-Fisher syndrome
      (MFS) and discusses the spectrum of GQ 1b-positive oculomotor nerve diseases,
      including MFS, Bickerstaff's brainstem encephalitis, Guillain-Barre syndrome,
      ophthalmoplegia without ataxia and isolated oculomotor palsies.

PMID- 21077018
TI  - [Optic neuropathy with concentric visual field constriction following life
      threatening H 1N1-infection].

PMID- 21077019
TI  - [Internal ophthalmoplegia: first sign of compressive third cranial nerve palsy?].

PMID- 21077020
TI  - [The ocular surfactant system and its relevance in the dry eye].
AB  - The amphiphilic surfactant proteins B (SP-B) and C (SP-C) are tightly bound to
      phospholipids. These proteins play important roles in maintaining the surface
      tension-lowering properties of pulmonary surfactant. Surfactant protein A (SP-A)
      and D (SP-D) are hydrophilic and are thought to have a role in recycling
      surfactant and, especially, in improving host defense in the lung. Moreover, SP-A
      supports the hydrophobic surfactant proteins B and during surfactant subtype
      assembly and inhibits the secretion of lamellar bodies into the alveolar space.
      During recent years surfactant proteins have also been detected at locations
      outside the lung such as the lacrimal apparatus. In this review, the latest
      information regarding SP function and regulation in the human lacrimal system,
      the tear film and the ocular surface is summarised with regard to dry eye,
      rheological and antimicrobial properties of the tear film, tear outflow, certain
      disease states and possible therapeutic perspectives.

PMID- 21077021
TI  - [Corneal epitheliopathy following trabeculectomy with postoperative adjunctive 5
      fluorouracil].
AB  - PURPOSE: The success of trabeculectomy in glaucoma not sufficiently controlled by
      maximal medical therapy substantially depends on postoperative scarring of the
      filtering bleb. This process of scarring can be inhibited by antimetabolites like
      mitomycin C (MMC) and 5-fluorouracil (5-FU). The aim of this study is the
      evaluation of incidence and long-term outcome of corneal surface defects and
      intraocular pressure following MMC- or 5FU-trabeculectomy using different doses
      of postoperative 5FU. METHODS: A retrospective, non-randomised comparative study
      of 381 patients undergoing trabeculectomy with intraoperative application of
      either 5FU (group A, n = 169) or MMC (group B, n = 212) was performed. Based on
      the Wuerzburg bleb classification score (WBCS) for postoperative wound healing
      evaluation, 30 of these operations of group A (group B: n = 26) did not receive 5
      FU postoperatively (controls), 67 (93) received up to 7 postoperative injections
      of 5 mg 5 FU (normal dosage group), and 72 (93) received more than 7 injections
      (high dosage group). Surface epithelial defects were routinely assessed by slit
      lamp microscopy and fluorescein staining. Intraocular pressure (IOP) was measured
      by Goldmann applanation tonometry. RESULTS: In the normal dosage group the mean
      total dose of 5 FU was 25.8 +/- 9.1 mg in group A (group B: 28.4 +/- 7.5 mg) and
      in the high dosage group 54.2 +/- 10.9 mg 5 FU (51.7 +/- 11.8 mg), respectively.
      Increased doses of postoperative 5 FU induced more frequent corneal erosions in
      both groups. Corneal erosions were seen in controls in 16.7 % (26.9 %), in the
      normal dosage group in 55.2 % (47.3 %) and in the high dosage group in 77.8 %
      (59.1 %) in group A and group B, respectively. The incidence of a corneal erosion
      between group A and group B did not differ significantly (p = 0.074). The mean
      reduction of intraocular pressure in mmHg did not show a significant difference
      12 months after trabeculectomy between controls and postoperative 5-FU
      operations. CONCLUSION: In eyes with beginning scarring of the filtering bleb
      after trabeculectomy the subconjunctival injection of 5-FU allows a similar
      reduction of intraocular pressure as in eyes without scarring. Corneal
      epitheliopathy following trabeculectomy and postoperative 5 FU is dose-dependent
      with higher doses leading to a higher incidence of corneal erosions. As serious
      corneal long-term complications are rare, risk-benefit analysis justifies the
      application of 5-FU after filtrating glaucoma surgery.

PMID- 21077023
TI  - CT features of neutropenic enterocolitis in adult patients with hematological
      diseases undergoing chemotherapy.
AB  - PURPOSE: This study investigates the features of neutropenic enterocolitis (NE)
      in adults. MATERIALS AND METHODS: Chart and radiology report reviews were used to
      identify neutropenic patients with hematological diseases undergoing
      chemotherapy, who had CT scans for the clarification of abdominal symptoms
      between October 2003 and October 2009. Patients with any cause for enteritis
      other than NE were excluded. The scans were analyzed with respect to imaging
      features and location. Morphological findings were correlated with clinical data.
      RESULTS: Thirty-one patients with NE (median age 46 years; range 20 - 75) could
      be identified. Wall thickening and hyperemia could be found in all bowel segments
      from jejunum to rectum. The right hemicolon was the most frequent location in 19
      patients (61%). Involvement was generalized in 6 patients (19%) and segmental in
      25 cases (81%). The longer the duration of neutropenia, the more likely
      generalized involvement of the bowel was. In 8 patients who underwent CT follow
      up, the appearance of bowel segments had completely (n = 5) or partially (n = 3)
      returned to normal at the latest 14 days after the initial diagnosis. Eight
      patients (26%) died 1 - 78 days after NE, 7 of who had previously recovered from
      NE. CONCLUSION: CT findings are useful for the diagnosis of NE and should be
      considered even in the presence of isolated small bowel involvement. The terms NE
      and typhlitis should thus no longer be used synonymously.

PMID- 21077024
TI  - GAP production of TCM herbs in China.
AB  - In this paper, we briefly review international Good Agricultural Practice (GAP)
      regulations related to traditional Chinese medicine herbs (TCM herbs) and the
      background of the drafting process and the implementation of GAP for TCM herbs in
      China. We also have summarized progress and achievements since the implementation
      of GAP for TCM herbs in 2002. Up to 2010, a total of 99 GAP bases were formally
      adopted by GAP certification. They cover 22 provinces/municipalities, and 49
      species of TCM herbs are currently cultivated in these GAP bases. Finally, we
      discuss the main problems in GAP implementation for Chinese crude drugs and put
      forward some suggestions to tackle them.

PMID- 21077025
TI  - Toxicological risks of Chinese herbs.
AB  - As traditional Chinese medicine (TCM) has become more popular there have been
      increasing concerns about safety and potential toxicity of the Chinese materia
      medica (CMM) comprising plants, animal parts and minerals. The potential toxicity
      of many CMM is well recognised in TCM and to reduce risks use of some herbs is
      restricted whilst specific processing methods have been developed to modify the
      activities/toxicity of others. However adverse reactions have been reported, many
      of these are due misuse or abuse of Chinese medicine. The main problem remains
      products adulterated with pharmaceuticals for weight loss or erectile
      dysfunction. But some herbs have narrow therapeutic ranges (e.g., Aconitum
      species) so toxic effects are frequently reported. Toxic effects from chronic or
      cumulative dosing are difficult to detect in the traditional setting and recent
      reports have demonstrated the health problems from Aristolochia species. Despite
      safety concerns, Chinese medicine appears to be relatively safe with
      comparatively few reports of adverse reactions compared with overall drug
      reports. The wealth of information in the Chinese literature needs to be more
      widely available. As TCM is widely used by patients, improved pharmacovigilance
      and pharmacoepidemiology can contribute valuable safety information, relevant to
      clinical use.

PMID- 21077026
TI  - Modern European monographs for quality control of Chinese herbs.
AB  - The actual concern about the safety and efficacy of herbal drugs originating from
      traditional Chinese medicine (TCM) is based on observations that these medicinal
      plants may have a high risk potential due to insufficient definitions, problems
      with identity, purity and falsifications. No uniform legal status for these
      groups of herbal drugs currently exists in the European Union. For quality
      control, monographs for TCM herbs can mainly be found in the Pharmacopoeia of the
      Peoples Republic of China. Based on these facts the Commission of the European
      Pharmacopoeia decided in 2005 to establish TCM-herbal drug monographs for the
      most important medicinal plants imported from Far East. These new monographs had
      to be established and evaluated on the basis of existing monographs in the
      Chinese Pharmacopoeia (ChP), English edition 2005. Due to important differences
      in the overall features of EP and ChP, a simple adapt/adopt procedure was not
      feasible. Therefore, specialist groups were mandated with a corresponding working
      programme. Some results and actual problems related to this working programme
      will be presented and discussed.

PMID- 21077027
TI  - Cultivation and breeding of Chinese medicinal plants in Germany.
AB  - Chinese herbal medicine (CHM) is increasingly used in Germany and Europe. Due to
      the need for herbal drugs of consistent quality and reliable supply, methods for
      commercial field cultivation and post-harvest processing under south German
      conditions have been developed for selected plant species used in CHM since 1999.
      The project used an interdisciplinary approach covering all aspects from seed
      sourcing to medicinal application. This paper describes the outcome of the
      agricultural seed and field experiments, breeding program, botanical and chemical
      characterization of the experimental material, comparison of experimental and
      imported herbal material with respect to their pharmaceutical quality, transfer
      of production methods and plant material to specialized farmers, medicinal
      application and, finally, information for users along the chain of distribution
      about the benefits of the locally produced herbal material.

PMID- 21077028
TI  - [The new recomendation of the 7(th) edition of TNM classification for Lung Cancer
      in pathologic assesssment (pTNM)].

PMID- 21077029
TI  - [Recommendations on systemic treatment of non-small cell lung cancer and maligant
      pleural mesothelioma].

PMID- 21077030
TI  - [The results of molecular epidemiological investigations in patients infected
      with strains of the genus Acinetobacter].
AB  - INTRODUCTION: Acinetobacter spp. is an important opportunistic pathogen
      responsible for increasing number of nosocomial infections. The majority of
      infection are of epidemic origin, and treatment has become difficult because many
      strains are resistant to a wide range of antibiotics. The aim of this study was
      to investigate the local infections caused by various species of the genus
      Acinetobacter, occurring in the hospital wards IGiChP in periods of increased
      prevalence: August 2007 and February and March 2008. MATERIAL AND METHODS: Twenty
      three strains of Acinetobacter spp. were isolated from 19 patients residing in
      the same period and the same hospital ward (2007 - 13 strains from 11 patients,
      2008 - 10 strains from 8 patients). Acinetobacter isolates obtained from these
      patients were characterized by phenotypically methods and genotypically by
      arbitrarily primed PCR (AP-PCR). RESULTS: All strains of Acinetobacter (n = 23)
      were multi-drug resistant. Used AP-PCR method showed 10 genotypes among the all
      strains. Acinetobacter spp. strains cultivated in 2007 and 2008 belonged to one
      genotype, came from patients hospitalized on the same wards, which confirms the
      transmission of infection in the patient's residence. CONCLUSIONS: The same
      genotype Acinetobacter baumannii strains isolated from two patients in 2007, and
      two patients in 2008, showed the presence of bacteria in the hospital
      environment. In the present study, we also established the usefulness of AP-PCR
      in molecular epidemiological investigations.

PMID- 21077031
TI  - [Prevalence of home mechanical ventilation in Poland].
AB  - INTRODUCTION: Home mechanical ventilation (HMV) is increasingly used in the
      treatment of chronic respiratory failure thanks to rapid technological
      development, increasing number of elderly people and extension of indications.
      The aim of the study was to assess: prevalence of HMV in Poland, the proportions
      of lung disease and neuromuscular patients using HMV and the type of interface
      (invasive v. non-invasive). MATERIAL AND METHODS: The questionnaire was send to
      all institutions providing HMV in Poland and to regional departments of National
      Health System (NHS). RESULTS: All NHS departments responded. They reported 846
      HMV users, 31% of children. The prevalence of HMV in Poland was assessed as 2,2
      patient per 100.000 population without striking differences between provinces.
      Among 39 HMV centers in Poland 12 (31%) answered. They reported 206 patients (24%
      of all HMV users). Proportion of ventilation mode consisted of 59% (122 pts)
      treated via a tracheostomy and 41% (84 pts) with non invasive ventilation (NIV).
      168 patients (82%) had neuromuscular diseases (ND), majority of them muscular
      dystrophy - 57 patients ( 34% of ND) and amyotrophic lateral sclerosis - 39
      patients (23% of ND). There were only 38 patients (18%) with lung and thoracic
      cage diseases: 17 with COPD and 10 with kyphoscoliosis. CONCLUSIONS: The
      prevalence of HMV treatment in Poland has developed dramatically in the last
      decade, but is still very low comparing to other European countries, especially
      due to very low number of patients with lung and chest wall diseases. The
      prevalence of invasive mode of ventilation is extremely high. The most important
      factors which inhibit development of HMV in Poland are: omission of respiratory
      physicians in the process of qualification, lack of national guidelines,
      sophisticated demands for HMV providers. The awareness of the need of HMV
      especially in patients with respiratory failure due to obesity hypoventilation
      syndrome and restrictive lung diseases should be increased among chest
      physicians.

PMID- 21077033
TI  - [The new TNM classification in lung cancer].
AB  - This paper presents the new TNM classification in lung cancer and its history.
      Seventh edition of tumor, node, metastasis (TNM) classification in lung cancer
      has been published by the International Union Against Cancer (UICC) and the
      American Joint Committee on Cancer (AJCC) at the beginning of 2009. The changes
      were based upon the results of the international project of the International
      Association for the Study of Lung Cancer (IASLC). The database included 81.495
      patients from the entire world (68.463 with non-small cell lung cancer and 13.032
      with small cell lung cancer) treated with various modalities between 1990 and
      2000. The collected data were validated internally and externally. The tumor size
      was considered of prognostic relevance: T1 tumors were subdivided into T1a (<= 2
      cm) and T1b (> 2 cm - <= 3 cm), T2 tumors into T2a (> 3 cm - <= 5 cm) and T2b (>
      5 cm - <= 7 cm), and T2 tumors > 7 cm were reclassified as T3. Tumors with the
      additional nodules in the same lobe as the primary tumor were classified as T3,
      those with additional nodules in another ipsilateral lobe - as T4. There were no
      changes in N category. In the M category, M1 was subclassified into M1a
      (contralateral lung nodules and pleural dissemination) and M1b (distant
      metastasis). Large T2 tumors (T2bN0M0) were upstaged from IB to IIA, small T2
      tumors (T2aN1M0) were downstaged from the IIB to IIA and T4N0-N1M0 - from IIIB to
      IIIA. The TNM classification was also recommended for small cell lung cancer
      instead of previously used categories of limited and extensive disease.

PMID- 21077032
TI  - [Immigrants treated for tuberculosis in Mazovian Center for Treatment of Lung
      Diseases and Tuberculosis in Otwock].
AB  - INTRODUCTION: Migration of population contributes to the transmission of
      tuberculosis (TB), particularly multidrug-resistant tuberculosis. In the
      countries of Western Europe, the immigrants' inflow contributes to the
      deterioration of the epidemiological situation. Majority of newly detected TB
      cases in some countries were affirmed among immigrant and foreign born
      population. In Poland, this problem has not been investigated up to 2005. The aim
      of the study was the assessment of the occurrence of tuberculosis in foreigners
      treated in the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis in
      Otwock. MATERIAL AND METHODS: This work had a retrospective character. The number
      of cases of tuberculosis in foreigners admitted between 2002 and 2007 was
      calculated from the data base of the Mazovian Centre for Treatment of Lung
      Diseases and Tuberculosis; 125 patients, whose basic demographic data,
      bacteriological status and the radiological changes suggested TB, were included
      in the study. RESULTS: The foreigners made up to 0.5-1.7% all tuberculosis cases
      treated in Mazovian Centre for Treatment of Lung Diseases and Tuberculosis. Among
      confirmed cases, twenty four nationalities were seen. Nationals of the Russian
      Federation (coming from the Republic of Chechnya) formed the biggest group (24%),
      followed by the Vietnamese (21%) and the Ukrainians (12%). Most of all cases were
      young men (77%; average age - 34 years). Children made up to 12% of all cases.
      Tuberculosis of lungs was predominating, and there were culture confirmed
      extrapulmonary locations in 13.6% of cases. Bacteriological confirmation was
      achieved in 53% of cases, but up to 22.7% cases were resistant to one of the
      antituberculosis medicines and 13.6% was multidrug-resistant. CONCLUSIONS:
      Despite the fact, that foreigners made up a small proportion among all the
      patient treated for tuberculosis in Mazovia, their number systematically
      increases. High proportion of multidrug-resistant tuberculosis reported in
      foreign-born cases is a concern.

PMID- 21077034
TI  - [Updated recommendations on systemic treatment of non-small cell lung cancer and
      malignant pleural mesothelioma].

PMID- 21077035
TI  - [Searching for genes influencing tobacco smoking susceptibility].
AB  - Numerous studies indicate genetical background of susceptibility to tobacco
      smoking. The current review presents new achievements and perspectives in
      searching for genes involved in tobacco smoking and dependence, which have been
      described in recent years as a result of the development of molecular techniques.
      It has been emphasized that tobacco smoking is a complex, polygenic behavior.
      Presence of multiple gene-gene and gene-environment interactions makes it
      difficult to find a strong genetic association. The causes of inconsistency in
      the results of candidate gene association studies, as well as the new
      perspectives in searching for genetic determinants of tobacco smoking, are also
      widely discussed. In particular, the focus is on the genome-wide association
      studies which allow the complex analysis of links between thousands of single
      nucleotide polymorphisms with smoking phenotypes.

PMID- 21077036
TI  - [Consolidation therapy in advanced non-small cell lung cancer].
AB  - Standard management of advanced non-small cell lung cancer includes palliative
      chemotherapy, but its efficacy is modest. In most cases a few cycles of
      palliative chemotherapy are administered, as there is no evidence of benefit
      associated with prolonged treatment. Recently, there is an interest in a new
      approach including treatment continuation using cytotoxic compounds of proved
      efficacy in second-line treatment, such as docetaxel and pemetrexed, or targeted
      agents (erlotinib, gefitinib, cetuximab and bevacizumab). This review presents
      the current knowledge on this therapeutic strategy including the results of most
      relevant phase III studies and their metaanalyses.

PMID- 21077037
TI  - Primary Sjogren's Syndrome with two extraglandular sites involvement - case
      report.
AB  - Primary Sjogren's Syndrome (pSS) is a chronic, slowly progressive inflammatory
      autoimmune disorder, characterised by lymphocytic infiltration of the exocrine
      glands, leading to decrease of glandular secretion. In 40-60% of pSS patients,
      extraglandular disease develops. We present the case of a patient with two
      extraglandular sites involvement in the course of pSS manifesting with
      progressive respiratory and gastrointestinal symptoms.

PMID- 21077038
TI  - [Polish Respiratory Society session commemorating 100-years anniversary of the
      death of Robert Koch].

PMID- 21077039
TI  - ["Advances in Pneumonology" - over 20 years long tradition].

PMID- 21077040
TI  - [Freedom of choice entails responsibility of not doing harm to others].

PMID- 21077041
TI  - Visions in addiction medicine - also for pneumonologists?

PMID- 21077042
TI  - Negative dialysate to sodium gradient does not lead to intracellular volume
      expansion post hemodialysis.
AB  - INTRODUCTION: Intradialytic hypotension remains the most common complication of
      routine outpatient hemodialysis treatments. There is debate as to the optimum
      dialysate sodium concentration, with hypotonic dialysates potentially causing
      intracellular swelling and hypertonic ones intracellular dehydration. METHODS:
      Multi-frequency bioimpedance was used to assess extracellular and intracellular
      fluid volumes in 53 adult hemodialysis patients. Dialysate sodium was checked by
      ion electrophoresis. RESULTS: The mean decrease in extracellular volume and
      intracellular volumes were 1.01 +/-0.09 and 0.88 +/-0.18 kg, respectively. The
      median dialysate to sodium gradient was -3 mmol/L (-1 to -6), with a median
      dialysate sodium of 136 mmol/L (136-138). There was no association between
      changes in body fluid composition and sodium concentrations, or gradients. The
      mean difference between dialysate sodium prescribed and delivered was 2.4 +/-0.8
      mmol/L. CONCLUSIONS: In this study we were unable to demonstrate a relationship
      between predialysis serum sodium and the dialysate sodium prescribed and changes
      in extracellular or intracellular fluid volumes. However this study showed that
      using a negative sodium gradient, patients can be successfully ultrafiltrated
      without setting up intracompartmental fluid gradients. The caveat is that the
      prescribed dialysate to serum sodium gradient may differ from the actual
      gradient.

PMID- 21077043
TI  - Early gut barrier dysfunction in patients with severe acute pancreatitis:
      attenuated by continuous blood purification treatment.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of continuous
      blood purification (CBP) on early gut mucosal dysfunction in patients with severe
      acute pancreatitis (SAP). METHODS: Patients with SAP were randomized to receive
      24 hours of continuous veno-venous hemofiltration (CVVH; n = 33) or no CVVH (n =
      30). Blood samples were taken from the patients at 0, 6, 12, and 24 hours during
      CVVH therapy. Serum diamine oxidase (DAO) and endotoxin, epithelial permeability,
      transepithelial electrical resistance (TER) and F-actin rearrangement of the
      epithelial monolayer were used as the markers for the assessment of gut barrier
      function and the effect of CBP therapy in patients with SAP. RESULTS: Patients
      with SAP had increased levels of serum DAO, endotoxin, and epithelial
      permeability when compared with normal controls, and the increase was more
      pronounced in patients with organ dysfunction (p<0.01). F-actin rearrangement,
      loose cell-cell junction, and iNOS mRNA upregulation were found in all patients.
      After CBP treatment, Acute Physiology and Chronic Health Evaluation II score and
      SOFA score improved significantly; levels of serum DAO, endotoxin, and epithelial
      permeability decreased(p<0.05). CBP also significantly attenuated reorganization
      of actin and downregulated iNOS mRNA expression and NO production (p<0.05).
      CONCLUSIONS: CBP can not only improve the general conditions but also effectively
      improve gut barrier dysfunction. The beneficial effect of CBP on gut barrier
      dysfunction is associated with the improvement of cytoskeletal instability, by
      downregulating iNOS through the removal of excess proinflammatory factors.

PMID- 21077044
TI  - Infections in tunneled hemodialysis catheters in the subclavian vein.

PMID- 21077045
TI  - Inadvertent femoral endarterectomy: a complication from a suture-based vascular
      closure device.

PMID- 21077046
TI  - Preclinical results of a prosthetic, early-stick graft with functional
      endothelium.
AB  - PURPOSE: The purpose of this study was to evaluate the NanoVasc Vascular Graft in
      comparison with a marketed expanded polytetrafluoroethylene (ePTFE) graft, both
      in vitro and in vivo. The graft was evaluated for use as both a bypass and
      arteriovenous (AV) access graft. Early-stick capabilities and patency were the
      primary end points evaluated. METHODS: Third party, independent laboratories
      completed mechanical testing, biocompatibility, and preclinical data collection.
      An ovine carotid artery interposition model and a canine femoral AV access model
      were used to evaluate 5-mm and 6-mm internal diameter sizes, respectively.
      RESULTS: There was no statistical difference in either model between the NanoVasc
      and ePTFE grafts with respect to patency. Time to hemostasis after cannulation
      with a 16-gauge needle was achieved ~10 times faster with the NanoVasc graft
      (mean time 27 seconds) compared with ePTFE. Histological analysis demonstrated
      functional endothelialization (nitric oxide expression), positive wound healing
      (cellular infiltration into the wall of the graft), and hemocompatibility of the
      NanoVasc graft. CONCLUSIONS: The NanoVasc Vascular Graft is a strong candidate as
      a bypass and AV access graft. Its early-stick capabilities and patency rates are
      an attractive feature in comparison with current AV access grafts.

PMID- 21077047
TI  - Augmented balloon-assisted maturation (aBAM) for nonmaturing dialysis
      arteriovenous fistula.
AB  - PURPOSE: The surgically placed dialysis arteriovenous fistula (AVF) is considered
      by the Kidney Disease Outcomes Quality Initiative (KDOQI)and the Fistula First
      Breakthrough Initiative to be the ideal choice for hemodialysis access. A
      significant number of newly placed AVFs either slowly or never adequately mature
      sufficiently to provide for adequate dialysis. The balloon-assisted maturation
      (BAM) procedure utilizes serial angioplasty to promote and accelerate AVF
      maturation. We present a minimally invasive AVF maturation technique utilizing
      angioplasty, stent-graft, and coil embolization. METHODS: A 41-year-old white
      woman presented with an nonmaturing AVF with multiple venous outflow channels. An
      adequately functioning AVF was achieved after 2 treatments including coil
      embolization, angioplasty, and stent-graft placement. RESULTS: Adequate thrill
      and dialysis flow was achieved. Patient has done well during short-term follow-up
      without further intervention. CONCLUSIONS: BAM techniques can be an effective
      tool to help a dialysis patient achieve an adequately mature AVF. Additional
      vascular interventional techniques may be utilized to further improve clinical
      results. For the purpose of this report we call this technique "augmented balloon
      assisted maturation," or aBAM.

PMID- 21077051
TI  - Luminescent porous silica fibers as drug carriers.
AB  - Luminescent and porous silica fibers have been successfully prepared by using the
      electrospinning process. The obtained multifunctional silica fibers, which
      possess a porous structure and display blue luminescence, can serve as a drug
      delivery host carrier, using ibuprofen (IBU) as a model drug, allowing the
      investigation of storage/release properties. Scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy
      (FT-IR), N(2) adsorption/desorption, photoluminescence (PL) spectra, and kinetic
      decay were used to characterize the structural, morphological, and optical
      properties of the as-obtained samples. The results reveal that the
      multifunctional silica materials exhibit an irregular porous structure, and
      display a fiberlike morphology with dimensions of several hundred nanometers in
      width and several millimeters in length. The obtained silica fibers exhibit an
      intense broad bluish emission, which might be attributed to impurities and/or
      defects in the silica fibers. The IBU-loaded silica fiber system shows blue
      luminescence under UV irradiation and controlled release behavior for IBU. In
      addition, the emission intensities of silica fibers in the drug carrier system
      vary with the released amount of IBU, thus allowing the drug release to be easily
      tracked and monitored by the change of the luminescence intensity.

PMID- 21077055
TI  - Nanoscale self-hosting of molecular spin-states in the intermediate phase of a
      spin-crossover material.
AB  - A new spin-crossover (SC) complex [Fe(II)H(2)L(2-Me)][AsF(6)](2) has been
      synthesized, in which H(2)L(2-Me) denotes the chirogenic hexadentate N(6) Schiff
      base ligand bis{[(2-methylimidazol-4-yl)methylidene]-3
      aminopropyl}ethylenediamine. This complex has revealed a rich variety of phases
      during its two-step thermal crossover, as well as photoinduced spin-state
      switching. A high-symmetry high-spin (HS, S=2) phase, a low-symmetry low-spin
      (LS, S=0) phase, an intermediate phase characterized by an unprecedented lozenge
      pattern of 12 predominantly HS molecular crystallographic sites confining 18
      predominantly LS molecular crystallographic sites, and a photoinduced low
      symmetry HS phase have been accurately evidenced by temperature-dependent
      magnetic susceptibility, Mossbauer spectroscopy, and crystallographic studies.
      This variety of phases illustrates the multi-stability of this system, which
      results from coupling between the electronic states and structural instabilities.

PMID- 21077057
TI  - Molecular mechanisms of aluminum oxide thin film growth on polystyrene during
      atomic layer deposition.

PMID- 21077058
TI  - Facile glycoenzyme wiring to electrode supports by redox-active biosupramolecular
      glue.

PMID- 21077059
TI  - Tri- and tetraurea piperazine cyclophanes: synthesis and complexation studies of
      preorganized and folded receptor molecules.
AB  - A series of symmetrical tri- and tetrameric N-ethyl- and N-phenylurea
      functionalized cyclophanes have been prepared in nearly quantitative yields (86
      99 %) from the corresponding tri- and tetraamino-functionalized piperazine
      cyclophanes and ethyl or phenyl isocyanates. Their conformational and
      complexation properties have been studied by single-crystal X-ray diffraction,
      variable-temperature NMR spectroscopy, and ESI-MS analysis. The rigid 27-membered
      trimeric cyclophane skeleton assisted by a seam of intramolecular hydrogen bonds
      results in a preorganized ditopic recognition site with an all-syn conformation
      of the urea moieties that, complemented by a lipophilic cavity of the cyclophane,
      binds molecular and ionic guests as well as ion pairs. The all-syn conformation
      persists in acidic conditions and the triprotonated triurea cyclophane binds an
      unprecedented anion pair, H(2)PO(4)(-)???HPO(4)(2-), in the solid state. The
      tetra-N-ethylurea cyclophane is less rigid and demonstrates an induced-fit
      recognition of diisopropyl ether in the solid state. The guest was encapsulated
      within the lipophilic interior of a quasicapsule, formed by intramolecular
      hydrogen-bond-driven folding of the 36-membered cyclophane skeleton. In the gas
      phase, the essential role of the urea moieties in the binding was demonstrated by
      the formation of monomeric 1:1 complexes with K(+), TMA(+), and TMP(+) as well as
      the ion-pair complexes [KI+K](+), [TMABr+TMA](+) and [TMPBr+TMP](+). In the
      positive-mode ESI-MS analysis, ion-pair binding was found to be more pronounced
      with the larger tetraurea cyclophanes. In the negative mode, owing to the large
      size of the binding site, a general binding preference towards larger anions,
      such as the iodide, over smaller anions, such as the fluoride, was observed.

PMID- 21077060
TI  - C2-symmetric chiral disulfoxide ligands in rhodium-catalyzed 1,4-addition: from
      ligand synthesis to the enantioselection pathway.
AB  - A family of chiral C(2)-symmetric disulfoxide ligands possessing biaryl
      atropisomeric backbones has been synthesized by using the Andersen methodology.
      Complete characterization includes X-ray crystallographic studies of all ligands
      and some of their rhodium complexes. Their synthesis, optical purity, electronic
      properties, and catalytic behavior in the prototypical rhodium-catalyzed 1,4
      addition of phenylboronic acid to 2-cyclohexen-1-one are presented through an in
      depth study of this ligand class. Density functional theory calculations on the
      step of the catalytic cycle that determines the enantioselectivity are presented
      and reinforce the first hypothetical explanations for the high levels of
      asymmetric induction observed.

PMID- 21077063
TI  - The handy use of Brown's P2-Ni catalyst for a skipped diyne deuteration:
      application to the synthesis of a [D4]-labeled F4t-neuroprostane.

PMID- 21077064
TI  - Probing the biology of natural products: molecular editing by diverted total
      synthesis.
AB  - The systematic modification of natural products through diverted total synthesis
      is a powerful concept for the systematic modification of natural products with
      the aim of studying mechanistic aspects of their biological activity. This
      concept offers far-reaching opportunities for discovery at the interface of
      biology and chemistry. It is underpinned by the power of chemical synthesis,
      which manifests itself in the ability to modify structure at will. Its
      implementation, when combined with innovative design, enables the preparation of
      unique mechanistic probes that can be decisive in differentiating and validating
      biological hypotheses at the molecular level. This Review assembles a collection
      of classic and current cases that illustrate and underscore the scientific
      possibilities for practitioners of chemical synthesis.

PMID- 21077067
TI  - Antisymbiotic self-assembly and dynamic behavior of metallamacrocycles with
      allylic corners.

PMID- 21077068
TI  - Surface-bound microenclosures for biomolecules.

PMID- 21077066
TI  - Surface modification of polymeric micelles by strain-promoted alkyne-azide
      cycloadditions.
AB  - Organomicelles modified by surface dibenzylcyclooctyne moieties can conveniently
      be functionalized by strain-promoted alkyne-azide cycloadditions. The ligation
      approach is highly efficient, does not require toxic reagents and is compatible
      with a wide variety of functional modules. Interactions of proteins with surface
      ligands of the micelles have been studied by AFM, which revealed that it leads to
      disassembly of the particles thereby providing a mechanism for triggered drug
      release.

PMID- 21077070
TI  - On the problem of comparing rates or apparent quantum yields in heterogeneous
      photocatalysis.

PMID- 21077069
TI  - Johannes Diderik van der Waals: a pioneer in the molecular sciences and Nobel
      Prize Winner in 1910.

PMID- 21077071
TI  - Ruthenium and osmium metalloradicals.

PMID- 21077072
TI  - Self-assembled synthetic viral capsids from a 24-mer viral peptide fragment.

PMID- 21077074
TI  - Chiral Bronsted acid catalyzed pinacol rearrangement.

PMID- 21077075
TI  - Layer-by-layer films of graphene and ionic liquids for highly selective gas
      sensing.

PMID- 21077076
TI  - Cubic mesoporous graphitic carbon(IV) nitride: an all-in-one chemosensor for
      selective optical sensing of metal ions.

PMID- 21077077
TI  - Two-dimensional ultraviolet (2DUV) spectroscopic tools for identifying
      fibrillation propensity of protein residue sequences.

PMID- 21077079
TI  - Intermolecular N-heterocyclic carbene catalyzed hydroacylation of arynes.

PMID- 21077078
TI  - Concise total synthesis of sintokamides A, B, and E by a unified, protecting
      group-free strategy.

PMID- 21077080
TI  - Rapid room-temperature synthesis of zeolitic imidazolate frameworks by using
      mechanochemistry.

PMID- 21077082
TI  - Computed tomography in color: NanoK-enhanced spectral CT molecular imaging.

PMID- 21077085
TI  - Mechanism of proton relaxation for enzyme-manipulated, multicomponent gold
      magnetic nanoparticle chains.
AB  - Longitudinal and transverse relaxation times of multicomponent nanoparticle (NP)
      chains are investigated for their potential use as multifunctional imaging agents
      in magnetic resonance imaging (MRI). Gold NPs (ca. 5 nm) are arranged linearly
      along double-stranded DNA, creating gold NP chains. After cutting gold NP chains
      with restriction enzymes (EcoRI or BamHI), multicomponent NP chains are formed
      through a ligation reaction with enzyme-cut, superparamagnetic NP chains. We
      evaluate the changes in relaxation times for different constructs of gold-iron
      oxide NP chains and gold-cobalt iron oxide NP chains using 300 MHz (1)H NMR. In
      addition, the mechanism of proton relaxation for multicomponent NP chains is
      examined. The results indicate that relaxation times are dependent on the one
      dimensional structure and the amount of superparamagnetic NP chains present in
      the multicomponent constructs. Multicomponent NP chains arranged on double
      stranded DNA provide a feasible method for fabrication of multifunctional imaging
      agents that improve relaxation times effectively for MRI applications.

PMID- 21077087
TI  - Surfactant-free self-assembly of nanocrystals into ellipsoidal architectures.
AB  - A simple approach to control the self-assembly of ZnS nanocrystals into well
      defined, uniform, three-dimensional, micrometer-scale, solid ellipsoidal
      structures with rattle-type, multishelled, and hollow architectures is presented.
      There is no surfactant or small molecule to assist the self-assembly of the
      nanocrystals. A possible mechanism of the controlled self-assembly is proposed.
      The growth process can be divided into two stages: 1) the formation of
      ellipsoidal architectures via oriented aggregation, the growth kinetics of which
      is primarily attributed to the charge-charge, charge-dipole, and dipole-dipole
      interactions of preformed ZnS nanocrystals; and 2) Ostwald ripening, which
      results in multishelled, rattle-type, and hollow structures. This self-assembly
      concept is also applicable to other metal sulfides.

PMID- 21077088
TI  - Cyclization of synthetic seco-proansamitocins to ansamitocin macrolactams by
      Actinosynnema pretiosum as biocatalyst.

PMID- 21077089
TI  - Antimicrobial peptides and their superior fluorinated analogues: structure
      activity relationships as revealed by NMR spectroscopy and MD calculations.
AB  - The conformations of two synthetic pentapeptides with antimicrobial activity and
      their 4-fluorophenylalanine (Pff)-containing analogues (ArXArXAr-NH(2); Ar=Phe,
      Pff; X=Lys, Arg) have been studied. NMR experiments carried out both in aqueous
      fluoroalcohol solutions and SDS micelles permitted their interactions with
      membrane-like environments to be explored. WaterLOGSY experiments and Mn(2+)
      based paramagnetic probes were also applied to assess their orientations with
      respect to the SDS micelles. In addition, pulse-field gradient (PFG) diffusion
      NMR spectroscopy studies were conducted, under different experimental conditions
      (i.e., concentration, temperature) to characterize the possible changes in the
      peptides' aggregation states as a putative critical factor for their
      antimicrobial activity. Finally, molecular dynamics simulations on a variety of
      conformations showed the intrinsic flexibility of these peptides in both aqueous
      solutions and membrane-mimetic systems.

PMID- 21077090
TI  - Linking chemical and microbial diversity in marine sponges: possible role for
      poribacteria as producers of methyl-branched fatty acids.
AB  - Many marine sponges contain massive numbers of largely uncultivated,
      phylogenetically diverse bacteria that seem to be important contributors to the
      chemistry of these animals. Insights into the diversity, origin, distribution,
      and function of their metabolic gene communities are crucial to dissect the
      chemical ecology and biotechnological potential of sponge symbionts. This study
      reveals a sharp dichotomy between high and low microbial abundance sponges with
      respect to polyketide synthase (PKS) gene content, the presence of methyl
      branched fatty acids, and the presence of members of the symbiotic candidate
      phylum "Poribacteria". For the symbiont-rich sponge Cacospongia mycofijiensis, a
      source of the tubulin-inhibiting fijianolides (=laulimalides), near-exhaustive
      large-scale sequencing of PKS gene-derived PCR amplicons was conducted. Although
      these amplicons exhibit high diversity at the sequence level, almost all of them
      belong to a single, architecturally unique group of PKSs present in
      "Poribacteria" and are proposed to synthesize methyl-branched fatty acids. Three
      components of this PKS were studied in vitro, providing initial insight into its
      biochemistry.

PMID- 21077091
TI  - Reversible carrier-type transitions in gas-sensing oxides and nanostructures.
AB  - Despite many important applications of alpha-Fe(2)O(3) and Fe doped SnO(2) in
      semiconductors, catalysis, sensors, clinical diagnosis and treatments, one
      fundamental issue that is crucial to these applications remains theoretically
      equivocal--the reversible carrier-type transition between n- and p-type
      conductivities during gas-sensing operations. Herein, we present an unambiguous
      and rigorous theoretical analysis in order to explain why and how the oxygen
      vacancies affect the n-type semiconductors alpha-Fe(2)O(3) and Fe-doped SnO(2),
      in which they are both electronically and chemically transformed into a p-type
      semiconductor. Furthermore, this reversible transition also occurs on the oxide
      surfaces during gas-sensing operation due to physisorbed gas molecules (without
      any chemical reaction). We make use of the ionization energy theory and its
      renormalized ionic displacement polarizability functional to reclassify,
      generalize and explain the concept of carrier-type transition in solids, and
      during gas-sensing operation. The origin of such a transition is associated with
      the change in ionic polarizability and the valence states of cations in the
      presence of oxygen vacancies and physisorped gas molecules.

PMID- 21077093
TI  - High-resolution surface chemical analysis of a trifunctional pattern made by
      sequential colloidal shadowing.
AB  - We present a new method for creating surface chemical patterns where three
      chemistries can be periodically arranged at alternate positions on a single
      substrate without the use of top-down approaches. High-resolution chemical
      imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS), with
      nanometer spatial resolution, is used to prove the success of the patterning and
      subsequent chemical modification steps. We use a combination of colloidal self
      assembly, plasma etching, self-assembled monolayers (SAMs) and physical vapour
      deposition (PVD). The method utilizes a double colloid assembly process in which
      a first layer of close-packed colloids is created, followed by plasma etching,
      coating with gold and deposition of a first SAM layer. A second particle layer is
      deposited on top of the first layer masking the interstitial spaces containing
      the first SAM. A second gold layer is deposited followed by a second SAM. After
      particle removal the surface consists of the pattern containing two different
      SAMs and a SiO(2) layer that can be readily functionalized with silanes. The
      possibility in the replacement of the two different thiols is investigated by X
      ray photoelectron spectroscopy (XPS) and it was found that no replacement is
      taking place. ToF-SIMS imaging is used to show the periodicity of the chemical
      patterns by tracking unique fragment ions from the different surface regions. The
      patterning method is adaptable to create smaller or larger chemical patterns by
      appropriate choice of particle sizes. The patterns are useful for immobilizing
      biomolecules for cell studies or as multiplexed biosensors.

PMID- 21077094
TI  - Regioselective ring-opening of amino acid-derived chiral aziridines: an easy
      access to cis-2,5-disubstituted chiral piperazines.
AB  - An efficient four-step synthetic strategy for cis-2,5-disubstituted chiral
      piperazines derived from amino-acid-based aziridines is described. The key steps
      in this strategy are the highly regioselective boron trifluoride diethyl etherate
      (BF(3).OEt(2))-mediated ring-opening of less-reactive N-Ts chiral aziridines by
      alpha-amino acid methyl ester hydrochloride followed by Mitsunobu cyclization.
      This protocol has been used in an attempt to construct the piperazine core
      framework of natural product (+)-piperazinomycin.

PMID- 21077095
TI  - Enantioselective and regioselective organocatalytic conjugate addition of
      malonates to nitroenynes.
AB  - The first catalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to
      nitroenynes catalyzed by cinchona alkaloid-based thiourea organocatalysts has
      been developed. The 1,4-addition adducts were obtained solely, in moderate to
      good yields (up to 93%) with good enantioselectivities (up to 99% ee). This
      protocol affords a conceptually different entry to the precursors of
      pharmaceutically important chiral beta-alkynyl acid derivatives and synthetically
      useful chiral nitroalkynes. Notably, the protocol worked well with both aryl- and
      alkyl-substituted alkynyl substrates.

PMID- 21077096
TI  - Self-assembled gels for biomedical applications.
AB  - Natural and synthetic gel-like materials have featured heavily in the development
      of biomaterials for wound healing and other tissue-engineering purposes. More
      recently, molecular gels have been designed and tailored for the same purpose.
      When mixed with, or conjugated to therapeutic drugs or bioactive molecules, these
      materials hold great promise for treating/curing life-threatening and
      degenerative diseases, such as cancer, osteoarthritis, and neural injuries. This
      focus review explores the latest advances in this field and concentrates on self
      assembled gels formed under aqueous conditions (i.e., self-assembled hydrogels),
      and critically compares their performance within different biomedical
      applications, including three-dimensional cell-culture studies, drug delivery,
      and tissue engineering. Although stability and toxicity issues still need to be
      addressed in more detail, it is clear from the work reviewed here that self
      assembled gels have a bright future as novel biomaterials.

PMID- 21077100
TI  - Catalytic oxidative dehydration of glycerol over a catalyst with iron oxide
      domains embedded in an iron orthovanadate phase.
AB  - An embedded catalyst for the oxidative dehydration of glycerol, featuring iron
      oxide (FeO(x)) domains on the surface of an iron orthovanadate (FeVO4) phase, is
      developed. Catalytic reactions are conducted in a fixed-bed reactor at 300 
      degrees C with a feed composition N2/O2/H2O/glycerol=66.6:1.7:30.3:1.5. Catalytic
      results show that the catalyst exhibits a better performance than an FeO(x)
      catalyst prepared by impregnation and than a mixture of FeVO4 and Fe2O3The best
      yield for acrylic acid was 14 %. The presence of FeO(x) domains on the surface of
      FeVO4 catalyzes the oxidation of acrolein to acrylic acid. The catalysts are
      characterized by a range of techniques. The interaction between the nanometer
      sized FeO(x) domains and the FeVO4 phase is strong enough to stabilize the FeO(x)
      and retain its high activity. The proximity of the two phases provides an
      environment for the dehydration of glycerol and the oxidation of acrolein to
      acrylic acid.

PMID- 21077101
TI  - Glycogen hyperphosphorylation underlies lafora body formation.
AB  - OBJECTIVE: Glycogen, the largest cytosolic macromolecule, acquires solubility,
      essential to its function, through extreme branching. Lafora bodies are
      aggregates of polyglucosan, a long, linear, poorly branched, and insoluble form
      of glycogen. Lafora bodies occupy vast numbers of neuronal dendrites and
      perikarya in Lafora disease in time-dependent fashion, leading to intractable and
      fatal progressive myoclonus epilepsy. Lafora disease is caused by deficiency of
      either the laforin glycogen phosphatase or the malin E3 ubiquitin ligase. The 2
      leading hypotheses of Lafora body formation are: (1) increased glycogen synthase
      activity extends glycogen strands too rapidly to allow adequate branching,
      resulting in polyglucosans; and (2) increased glycogen phosphate leads to
      glycogen conformational change, unfolding, precipitation, and conversion to
      polyglucosan. Recently, it was shown that in the laforin phosphatase-deficient
      form of Lafora disease, there is no increase in glycogen synthase, but there is a
      dramatic increase in glycogen phosphate, with subsequent conversion of glycogen
      to polyglucosan. Here, we determine whether Lafora bodies in the malin ubiquitin
      ligase-deficient form of the disease are due to increased glycogen synthase or
      increased glycogen phosphate. METHODS: We generated malin-deficient mice and
      tested the 2 hypotheses. RESULTS: Malin-deficient mice precisely replicate the
      pathology of Lafora disease with Lafora body formation in skeletal muscle, liver,
      and brain, and in the latter in the pathognomonic perikaryal and dendritic
      locations. Glycogen synthase quantity and activity are unchanged. There is a
      highly significant increase in glycogen phosphate. INTERPRETATION: We identify a
      single common modification, glycogen hyperphosphorylation, as the root cause of
      Lafora body pathogenesis.

PMID- 21077111
TI  - In silico prediction of potential metallothioneins and metallohistins in
      actinobacteria.
AB  - Metallothioneins and metallohistins are short peptides with a high cysteine
      and/or histidine content able to coordinate metals intracellularly, thereby
      increasing the tolerance against elevated concentrations of metals. Because of
      their features, they can be detected by in silico prediction from proteomes
      annotated from sequenced genomes. Here, we analyzed 73 sequenced actinobacterial
      genomes for peptides (<= 100 amino acids) with a high content of cysteine and
      histidine (>= 15%) and identified 103 putative metallothioneins and
      metallohistins. For 45 of these peptides, we found similarities to metal binding
      protein domains, including zinc fingers, heavy metal transporters or eukaryotic
      metallothioneins, which can serve as proof-of-principle in underscoring a
      potential function as metal binding peptides. An evolutionary origin from metal
      containing domains of enzymes is discussed and metallohistins not containing
      cysteine are described for the first time for bacteria.

PMID- 21077112
TI  - Bacterial tolerance to silver nanoparticles (SNPs): aeromonas punctata isolated
      from sewage environment.
AB  - Use of silver nanoparticles (SNPs) is increasing in a large number of consumer
      products. Thus, the possible build-up of the nanoparticles in the environment is
      becoming a major concern. Aeromonas punctata isolated from sewage showed
      tolerance to 200 MUg/ml SNPs. The growth kinetics data for A. punctata treated
      with nanoparticles were similar to those in the absence of nanoparticles. There
      was a reduction in the amount of exopolysaccharides (EPS) in bacterial culture
      supernatant after nanoparticle-supernatant interaction. EPS capping of the
      nanoparticles was confirmed by UV-visible, XRD and comparative FTIR analysis. The
      EPS-capped SNPs showed less toxicity to Escherichia coli, Staphylococcus aureus
      and Micrococcus luteus compared to the uncapped ones. The study suggests capping
      of nanoparticles by bacterially produced EPS as a probable physiological defense
      mechanism.

PMID- 21077113
TI  - Identification of new galactose oxidase genes in Fusarium spp.
AB  - Galactose oxidase (GO) converts galactose to an aldehyde and has several
      biotechnological applications, including cancer diagnosis. It is mainly produced
      by Fusarium austroamericanum but is also produced by Fusarium acuminatum and by
      isolates of the Fusarium graminearum and Gibberella fujikuroi complexes. The F.
      austroamericanum GO gaoA gene has been cloned, but the GO genes from other
      secreting species have not been characterized. Problems associated with the F.
      austroamericanum GO such as high pI and low catalytic efficiency and
      thermostability, and the difficult purification process makes the search for
      homologous genes attractive. In this work, the GO genes from Fusarium
      verticillioides and Fusarium subglutinans, two species of the G. fujikuroi
      complex, were cloned, sequenced, and analyzed. New GO genes were found in
      databases and were used to construct a phylogenetic tree, which revealed the
      existence of three orthologous lineages of GO genes in Fusarium spp. In addition,
      RT-PCR analyses revealed that the new GO cloned gene may be endogenously
      expressed in F. subglutinans but not in F. verticillioides, in the used culture
      conditions.

PMID- 21077114
TI  - Diversity and phylogeny of plant growth-promoting bacilli from moderately acidic
      soil.
AB  - The molecular diversity of aerobic endospore-forming bacteria, typically Bacillus
      and its derived genera, has been investigated in various environments. However,
      there have been few investigations concerning Bacillus in acidic soils. In this
      study, the genotypic diversity and phylogenetic relationships among plant growth
      promoting (PGP) bacilli isolated from the rice rhizosphere growing in acidic
      soils of Kerala (pH varying from 6.3 to 6.8) were investigated. For assessing
      their biocontrol potential and PGP attributes, 115 isolates were randomly
      selected and 49 isolates that were positive for multiple traits were selected.
      Metabolic characterization of representative strains, using the Biolog GP2 (Gram
      Positive) MicroPlate(TM) , revealed a large versatility with respect to
      carbohydrate utilization. Amplified ribosomal DNA restriction analysis revealed
      13 clusters at 65% similarity level, which consisted of 1-21 strains. 16S rDNA
      partial sequencing assigned all the isolates, except for one, to the Bacillus
      genus, with close relatedness to Bacillus humi, B. megaterium, B. drentensis, B.
      pocheonensis, B. aestuarii, B. arbutinivorans, B. niacini, and Brevibacterium
      casei. The Bacillus species with different metabolic capabilities, PGP abilities,
      and genetic diversity found in this study are likely to have ecological
      relevance.

PMID- 21077115
TI  - Phylogenetic analysis and antimicrobial activities of Streptomyces isolates from
      mangrove sediment.
AB  - The phylogeny of members of Streptomyces bacteria isolated from mangrove
      sediments in the Manakudi estuary near the Arabian Sea, India, was analyzed in
      the present study. Among the 35 different isolates, five organisms, JS-9, JS-11,
      JS-12, JS-13 and JS-20, exhibited potent antimicrobial effects against
      methicillin-resistant Staphylococcus aureus (clinical isolate) and methicillin
      susceptible S. aureus MTCC 3160 and Salmonella typhi MTCC 733; all other isolates
      displayed intermediate antimicrobial effects. RFLP analysis of HaeIII and BstUI
      double-digested 16S rRNA gene fragments of the isolates were distinguished into
      20 distinct RFLP types, with the genetic similarity coefficient varying from 0.57
      to 0.97. On average, 17 RFLP markers were observed from approximately 50 to 350
      bp size and all the RFLP types showed significant genetic polymorphism by
      clustering into three major clusters. Phylogenetic analysis showed that the 20
      member Streptomyces isolates were divided into three major clusters and they
      shared 97.2-99.8% sequence identity to the 16S rRNA gene sequences of the
      Streptomyces taxons of marine origin. The distribution of the isolates revealed
      that the distinct Streptomyces groups were clustered in the phylogenetic tree and
      there was a good correlation between the diversity of the antimicrobial phenotype
      and that of the 16S rRNA gene.

PMID- 21077116
TI  - Anoxybacillus salavatliensis sp. nov., an alpha-glucosidase producing,
      thermophilic bacterium isolated from Salavatli, Turkey.
AB  - A novel moderately thermophilic, Gram-positive staining, rod-shaped, spore
      forming, motile, facultative anaerobic, and alpha-glucosidase producing strain
      A343(T), was isolated from a high temperature well-pipeline sediment sample in
      Salavatli province of Aydin, Turkey. Growth was observed at 37-69 oC (optimum 60 
      degrees C), at pH 5.5-9.5 (optimum 8.0-9.0) and at salinities from 0 to 4.5%
      (w/v) (optimum 2%). Strain A343(T) was able to grow on a wide range of carbon
      sources. Gelatin and starch utilization, amylase, catalase and oxidase
      activities, reduction of nitrate to nitrite were all positive. The G+C content of
      the genomic DNA was 45.1 mol%. The major menaquinone was MK-7. The dominant
      cellular fatty acids were: iso-C15:0, C16:0, and iso-C17:0. The phylogenetic
      analysis based on the 16S rRNA gene sequence revealed that the strain A343(T)
      belonged to the genus Anoxybacillus. The 16S rRNA gene sequence similarity
      between strain A343(T) and the type strains of recognized Anoxybacillus species
      was ranged from 95.8 to 99.4%. DNA-DNA hybridization revealed low homology with
      its closest relative Anoxybacillus kamchatkensis (49.7%). In addition to the
      total cell protein profiles, the Rep-PCR and the intergenic 16S-23S rRNA gene
      fingerprinting profiles differentiated strain A343(T) from all of the reference
      Anoxybacillus species used. Based upon phenotypic, phylogenetic and
      chemotaxonomic evidence, strain A343(T) was assigned to a new species within the
      genus Anoxybacillus, A. salavatliensis sp. nov. (The type strain A343(T) = DSM
      22626(T) = NCIMB 14579(T)). The 16S rRNA gene nucleotide sequence of strain
      A343(T) is available in the GenBank database under the accession number-
      EU326496. Weinheim).

PMID- 21077117
TI  - Characterization of Bacillus thuringiensis isolates and their differential
      toxicity against Helicoverpa armigera populations.
AB  - Bacillus thuringiensis isolates were characterized in rhizospheric cotton soils
      by using acetate selection process from eight different locations in South India.
      The fact that B. thuringiensis indices were higher in proportion in soil samples
      taken from Tamil Nadu and Karnataka than from Andhra Pradesh, indicates the
      abundance of B. thuringiensis populations in the cotton rhizosphere. Biochemical
      typing of the isolates designated eight local isolates (BtNg13, BtCo1, BtHyb7,
      BtAm2, BtRm5, BtWr3, BtPl 4, BtN 9), which belong to subspecies kurstaki, the
      most prevalent subspecies. Toxicity assays on American boll worm larval (F(1) )
      populations collected from the Andhra Pradesh, Bangalore and Coimbatore regions,
      with a susceptible insect strain against different isolates of B. thuringiensis
      kurstaki spore-crystal mix, revealed distinct susceptibility patterns and
      specificity. The highest susceptibility was observed in the F(1) populations of
      Coimbatore, followed by Bangalore and Hyderabad populations, in comparison with
      the susceptible insect strain. Significant differences were observed (p < 0.0005
      and CD = 5.3975) among Btk local isolates, H. armigera biotypes, Btk spore
      crystal mix concentration and their interactions, through the Multifactorial
      ANOVA analysis. The toxicity of local B. thuringiensis isolates was higher than
      that of HD-1 (reference B.t.k strain). Indigenous Btk isolates have an enormous
      potential for the management of H. armigera in terms of development of resistance
      to HD-1. The present study would serve as a baseline data for future resistance
      monitoring of B. thuringiensis strains in H. armigera in Southern India.

PMID- 21077119
TI  - Abundance, diversity and antibiotics resistance pattern of Vibrio spp. in coral
      ecosystem of Kurusadai island.
AB  - The abundance and species diversity of Vibrio associated with coral reef
      ecosystem of Kurusadai island, Tamil Nadu, India were evaluated. A total of
      twelve sampling locations including different live and dead coral surfaces,
      surrounding water and rock surface (negative control) were selected for the
      present study. Total viable and TCBS counts were found to be higher in dead coral
      as compared to that of live coral. Out of total 21 species of Vibrio isolated, 13
      were identified up to species level based on biochemical tests and 16S rRNA gene
      sequence homology, while remaining 8 isolates did not show homology up to species
      level with any of the sequences available in the NCBI database. Moreover, these
      unidentified Vibrio spp. exhibited intra-species variation. This study indicated
      association of hitherto unknown Vibrio species with coral reef ecosystem of
      Kurusadai island. Assuming that only resistant bacteria can grow in the coral
      environment, susceptibility against a total of 20 antibiotics was evaluated. All
      the isolates exhibited resistance towards more than 6 antibiotics. Interestingly,
      none of the identified bacteria were previously reported to be of coral pathogen
      reflecting the healthy nature of the ecosystem. However, a continuous monitoring
      of the region will be prerequisite to envisage the role of these bacteria on the
      health status of the coral ecosystem.

PMID- 21077118
TI  - Production, characterization, cloning and sequence analysis of a monofunctional
      catalase from Serratia marcescens SYBC08.
AB  - A monofunctional catalase from Serratia marcescens SYBC08 produced by liquid
      state fermentation in 7 liter fermenter was isolated and purified by ammonium
      sulfate precipitation (ASP), ion exchange chromatography (IEC), and gel
      filtration (GF) and characterized. Its sequence was analyzed by LC-MS/MS
      technique and gene cloning. The highest catalase production (20,289 U . ml(-1))
      was achieved after incubation for 40 h. The purified catalase had an estimated
      molecular mass of 230 kDa, consisting of four identical subunits of 58 kDa. High
      specific activity of the catalase (199,584 U . mg(-1) protein) was 3.44 times
      higher than that of Halomonas sp. Sk1 catalase (57,900 U . mg(-1) protein). The
      enzyme without peroxidase activity was found to be an atypical electronic
      spectrum of monofunctional catalase. The apparent K(m) and V(max) were 78 mM and
      188, 212 per uM H(2) O(2) uM heme(-1) s(-1), respectivly. The enzyme displayed a
      broad pH activity range (pH 5.0-11.0), with optimal pH range of 7.0-9.0: It was
      most active at 20  degrees C and had 78% activity at 0  degrees C. Its thermo
      stability was slightly higher compared to that of commercial catalase from bovine
      liver. LC-MS/MS analysis confirmed that the deduced amino acid sequence of
      cloning gene was the catalase sequence from Serratia marcescens SYBC08. The
      sequence was compared with that of 23 related catalases. Although most of active
      site residues, NADPH-binding residues, proximal residues of the heme, distal
      residues of the heme and residues interacting with a water molecule in the enzyme
      were well conserved in 23 related catalases, weakly conserved residues were
      found. Its sequence was closely related with that of catalases from pathogenic
      bacterium in the family Enterobacteriaceae. This result imply that the enzyme
      with high specific activity plays a significant role in preventing those
      microorganisms of the family Enterobacteriaceae against hydrogen peroxide
      resulted in cellular damage. Calalase yield by Serratia marcescens SYBC08 has
      potential industrial application in scavenging hydrogen peroxide.

PMID- 21077121
TI  - Evaluation of the interspecific competitive ability of the bioincising fungus
      Physisporinus vitreus.
AB  - A hierarchical set of assays were used to evaluate the interspecific competitive
      ability of the bioincising fungus Physiporinus vitreus (response species). The
      competitiveness and growth mode of P. vitreus against a range of blue stain fungi
      and Trichoderma species (challenge species) was investigated in dual culture
      tests (a) and a spatially heterogeneous system of tessellation agar (b) on
      different media. In addition, the robustness of the bioincising process against
      biotic influences was determined by controlled interaction tests with different
      inocula of the challenge species (colony-forming units: 10(2), 10(4), 10(6) ml(
      1)) on Norway spruce (Picea abies Karst.) heartwood. The results of the dual
      culture and tessellation agar tests revealed a significant (P <= 0.001)
      antagonistic potential (lethal effect) of the T. atroviride strain (15603.1),
      whereas no or only a slight effect of the blue stain fungi on P. vitreus was
      detectable. The interaction tests on Norway spruce heartwood confirmed that an
      increase in inoculum size of the challenge fungi correlated with an increased
      negative effect (Spearman's rho coefficient (rho) = -0.521). Among the challenge
      species, T-15603.1 revealed the most negative effect on the homogeneous
      development of P. vitreus on wood and thus on the outcome of the bioincising
      process. To improve the uniformity of colonization and to reduce the rate of
      contamination, the incubation of wood in a sealed system (bioreactor) after
      sterilization is suggested.

PMID- 21077122
TI  - Cellular roles of neuronal calcium sensor-1 and calcium/calmodulin-dependent
      kinases in fungi.
AB  - The neuronal calcium sensor-1 (NCS-1) possesses a consensus signal for N-terminal
      myristoylation and four EF-hand Ca(2+)-binding sites, and mediates the effects of
      cytosolic Ca(2+). Minute changes in free intracellular Ca(2+) are quickly
      transformed into changes in the activity of several kinases including
      calcium/calmodulin-dependent protein kinases (Ca(2+)/CaMKs) that are involved in
      regulating many eukaryotic cell functions. However, our current knowledge of NCS
      1 and Ca(2+)/CaMKs comes mostly from studies of the mammalian enzymes. Thus far
      very few fungal homologues of NCS-1 and Ca(2+)/CaMKs have been characterized and
      little is known about their cellular roles. In this minireview, we describe the
      known sequences, interactions with target proteins and cellular roles of NCS-1
      and Ca(2+)/CaMKs in fungi.

PMID- 21077123
TI  - Effectiveness of thiamethoxam and imidacloprid seed treatments against Bemisia
      tabaci (Hemiptera: Aleyrodidae) on cotton.
AB  - BACKGROUND: Bemisia tabaci (Gennadius) biotype B is one of the most important
      pests on cotton around the world. Laboratory, greenhouse and field experiments
      were conducted to determine the efficacy of thiamethoxam and imidacloprid seed
      treatments against B. tabaci on cotton. RESULTS: Under laboratory conditions, the
      two treatments caused whitefly adult mortality, reduced oviposition and increased
      mortality of nymphs at 10, 20, 30 and 40 days after germination (DAG). The longer
      the adults fed on plants from treated seeds, the higher the mortality. The two
      treatments did not have any effect on eggs. The efficacy of the treated seeds
      against B. tabaci gradually decreased from 10 to 40 DAG, being the lowest at 40
      DAG. In laboratory experiments, the efficacies between the two treatments were
      similar. In greenhouse experiments, the two treatments were equally effective
      with lower numbers of whiteflies than untreated controls. With both treatments
      the concentrations of the active ingredient were gradually reduced with aging of
      the plants and from the bottom to the top leaves of the plants. Numbers of live
      whiteflies were well correlated with the dosage of active ingredients. Under
      field conditions, the seeds treated with both insecticides exhibited similar
      efficacy against B. tabaci for up to ~2 months. CONCLUSION: Cotton seeds treated
      with imidacloprid and thiamethoxam were effective against B. tabaci for up to 45
      days under laboratory and greenhouse conditions, and up to ~2 months under field
      conditions. Use of imidacloprid- and thiamethoxam-treated seeds can be an
      important alternative for management of whiteflies on cotton.

PMID- 21077124
TI  - Localisation of the benzimidazole fungicide binding site of Gibberella zeae beta2
      tubulin studied by site-directed mutagenesis.
AB  - BACKGROUND: The efficacy of benzimidazole fungicides is often limited by
      resistance, and this is the case with the use of carbendazim for controlling
      Fusarium head blight caused by Gibberella zeae (Schwein.) Petch (anamorph
      Fusarium graminearum). Recent studies have shown that carbendazim resistance in
      field strains of G. zeae is associated with mutations in the beta(2)-tubulin
      gene. The aims of the present study were to validate this mechanism and research
      the binding sites of carbendazim on beta(2)-tubulin. RESULTS: This work used site
      directed mutagenesis followed by gene replacement to change the beta(2)-tubulin
      gene of a carbendazim-sensitive field strain of G. zeae at residues 50, 167, 198
      or 200. The transformants were confirmed and tested for their sensitivity to
      carbendazim. All the mutants were resistant to carbendazim, but the level of
      resistance differed depending on the mutation. Biological characteristics did not
      differ between the field strain and the site-directed mutants. A three
      dimensional model of beta(2)-tubulin was constructed, and the possible
      carbendazim binding site was analysed. CONCLUSION: Mutations at codons 50, 167,
      198 and 200 of G. zeae beta(2)tub could cause resistance to carbendazim, and
      these codons may form a binding pocket.

PMID- 21077126
TI  - Development and applications of single-drop microextraction for pesticide residue
      analysis: A review.
AB  - Single-drop microextraction (SDME) has become more popular than other
      microextraction techniques because it is simple, cost-effective, easy to operate
      and nearly solvent-free. The technique has been employed successfully for trace
      analysis in environmental, biomedical and food applications. In view of the
      increasingly stringent regulatory limits for many pesticides, which are below the
      LOD of the existing instruments, SDME may provide a cost-effective solution for
      reducing the LOD of pesticides. The present review focuses on recent development
      in SDME technique, and its application coupled with various analytical
      techniques, such as GC-MS, GC and HPLC for pesticide residue analysis in
      different matrices. The advantages, limitations and outlook on the future of SDME
      technique for its wider applications are also discussed.

PMID- 21077127
TI  - Optimization of microwave-assisted extraction of polyphenols from apple pomace
      using response surface methodology and HPLC analysis.
AB  - A simple and efficient microwave-assisted extraction of polyphenols from
      industrial apple pomace was developed and optimized by the maximization of the
      yield using response surface methodology. A Box-Behnken design was used to
      monitor the effect of microwave power, extraction time, ethanol concentration and
      ratio of solvent to raw material (g/mL) on the polyphenols yield. The results
      showed that the optimal conditions were as follows: microwave power 650.4 W,
      extraction time 53.7 s, ethanol concentration 62.1% and ratio of solvent to raw
      material 22.9:1. Validation tests indicated that the actual yield of polyphenols
      was 62.68+/-0.35 mg gallic acid equivalents per 100 g dry apple pomace with
      RSD=0.86% (n=5) under the optimal conditions, which was in good agreement with
      the predicted yield and higher than those of reflux and ultrasonic-assisted
      extraction methods. HPLC analysis indicated that the major polyphenols of apple
      pomace consisted of chlorogenic acid, caffeic acid, syrigin, procyanidin B2, (-)
      epicatechin, cinnamic acid, coumaric acid, phlorizin and quercetin, of which
      procyanidin B2 had the highest content of 219.4 mg/kg.

PMID- 21077128
TI  - Combination of ultrasound-assisted ionic liquid dispersive liquid-phase
      microextraction and high performance liquid chromatography for the sensitive
      determination of benzoylureas pesticides in environmental water samples.
AB  - This paper describes a new method for rapid and sensitive determination of
      diflubenzuron, flufenoxuron, triflumuron and chlorfluazuron in water samples by
      ultrasound-assisted ionic liquid dispersive liquid-phase microextraction in
      combination with HPLC. Ionic liquid 1-hexyl-3-methylimidazolium
      hexafluorophosphate ([C(6)MIM][PF(6)]) was used as the extraction solvent for the
      enrichment of four benzoylurea (BU) pesticides. Factors such as volume of
      [C(6)MIM][PF(6)], sonication time, sample pH, extraction time, centrifuging time
      and salting-out effect were systematically investigated. Under the optimum
      conditions, an excellent linear relationship was achieved in the range of 1.0-100
      MUg/L. The detection limits varied from 0.21 to 0.45 MUg/L and the precision of
      the method was below 6.9% (RSD, n=6). The proposed method was successfully
      applied for the determination of these BU pesticides in water samples and
      excellent spiked recoveries were achieved. All these results demonstrated that
      this procedure provided a new simple, rapid, easy to operate, efficient and
      sensitive method for the analysis of BU pesticides in aqueous samples.

PMID- 21077129
TI  - Quality assessment of a formulated Chinese herbal decoction, Kaixinsan, by using
      rapid resolution liquid chromatography coupled with mass spectrometry: A chemical
      evaluation of different historical formulae.
AB  - Kaixinsan is an ancient Chinese herbal decoction mainly prescribed for patients
      suffering from mental depression. This decoction was created by Sun Si-miao of
      Tang Dynasty (A.D. 600) in ancient China, and was composed of four herbs: Radix
      and Rhizome Ginseng, Radix Polygalae, Rhizoma Acori Tatarinowii and Poria.
      Historically, this decoction has three different formulations, each recorded at a
      different point in time. In this study, the chemical compositions of all three
      Kaixinsan formulae were analyzed. By using rapid resolution LC coupled with a
      diode-array detector and an ESI triple quadrupole tandem MS (QQQ-MS/MS), the
      Radix and Rhizome Ginseng-derived ginsenosides including Rb(1), Rd, Re, Rg(1),
      the Radix Polygalae-derived 3,6'-disinapoyl sucrose, the Rhizoma Acori
      Tatarinowii-derived alpha- and beta-asarone and the Poria-derived pachymic acid
      were compared among the three different formulations. The results showed
      variations in the solubility of different chemicals between one formula and the
      others. This systematic method developed could be used for the quality assessment
      of this herbal decoction.

PMID- 21077120
TI  - High Archaea diversity in Varvara hot spring, Bulgaria.
AB  - The phylogeny of the latest recognized domain, Archaea, is still complicated and
      it is largely based on environmental sequences. A culture independent molecular
      phylogenetic analysis revealed high Archaea diversity in a terrestrial hot
      spring, village Varvara, Bulgaria. A total of 35 archaeal operational taxonomic
      units (OTUs) belonging to three of the classified five Archaea phyla were
      identified. Most of the sequences were affiliated with the phylum Crenarchaeota
      (23), grouped in four branches. The rest of the sequences showed highest
      similarity to the unidentified archaeal clones (9), Euryarchaeota (2), and
      "Korarchaeota " (1). Eight (23%) of the sequenced 16S rDNAs didn't have known
      close relatives and represented new and diverse OTUs, four of them forming a new
      archaeal subgroup without close described sequences or culturable relatives. A
      sequence affiliated with "Korarchaeota " showed low similarity (90%) to the
      closest neighbor and both sequences formed unique branch in this phylum.
      Consequently, the constructed archaeal libraries are characterized by (1) high
      proportion of OTUs representing uncultivated archaeal phylogroups, (2) the
      abundance of novel phylotype sequences, (3) the presence of high proportions of
      Crenarchaeota phylotypes unrelated to cultivated organisms and (4) the presence
      of a sequence only distantly related to "Korarchaeota " phylum.

PMID- 21077130
TI  - Determination of phthalate esters in soil by microemulsion electrokinetic
      chromatography coupled with accelerated solvent extraction.
AB  - A novel method using microemulsion electrokinetic chromatography combining
      accelerated solvent extraction was developed for quantitative analysis of six
      phthalate esters (PAEs) including dimethyl phthalate, diethyl phthalate, dibutyl
      phthalate, benzyl butyl phthalate, bis(2-ethylhexyl) phthalate, as well as
      dioctyl phthalate. The effect of each individual component within the
      microemulsions, i.e. oil phase, surfactant and co-surfactant on resolution of the
      analytes was systematically studied. Baseline separation of six PAEs was achieved
      within 26 min by using the microemulsion buffer containing a 60 mmol/L borate
      buffer at pH 9.0, 0.5% v/v n-octane as oil droplets, 100 mmol/L sodium cholate as
      surfactant and 5.0% v/v 1-butanol as co-surfactant. The purposed accelerated
      solvent extraction-microemulsion electrokinetic chromatography method was
      successfully applied to the determination of trace amount of PAEs in soil samples
      collected from three different fields in areas of Fujian Province and the
      contents of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzyl
      butyl phthalate, bis(2-ethylhexyl) phthalate and dioctyl phthalate were 0.63
      0.68, 0.32-0.63, 2.53-3.96, 0-1.75, 7.32-11.7 and 0-3.46mg/kg, respectively. It
      was validated that the results were consistent with those obtained by GC-MS
      method.

PMID- 21077135
TI  - Functional connectivity between cognitive control regions is sensitive to
      familial risk for ADHD.
AB  - Familial risk for attention-deficit hyperactivity disorder (ADHD) has been
      associated with changes in brain activity related to cognitive control. However,
      it is not clear whether changes in activation are the primary deficit or whether
      they are related to impaired communication between regions involved in this
      ability. We investigated whether (1) functional connectivity between regions
      involved in cognitive control was affected by familial risk and (2) changes were
      specific to these regions. Correlational seed analyses were used to investigate
      temporal covariance between cognitive control and motor regions in two
      independent samples of typically developing controls, subjects with ADHD and
      their unaffected siblings. In both samples, correlation coefficients between
      cognitive control regions were greater for typically developing controls than for
      subjects with ADHD, with intermediate values for unaffected siblings. Within the
      motor network, unaffected siblings showed correlations similar to typically
      developing children. There were no differences in activity between the brain
      regions involved. These data show that functional connectivity between cognitive
      control regions is sensitive to familial risk for ADHD. Results suggest that
      changes in connectivity associated with cognitive control may be suitable as an
      intermediate phenotype for future studies.

PMID- 21077136
TI  - Modulation of steady state functional connectivity in the default mode and
      working memory networks by cognitive load.
AB  - Interregional correlations between blood oxygen level dependent (BOLD) magnetic
      resonance imaging (fMRI) signals in the resting state have been interpreted as
      measures of connectivity across the brain. Here we investigate whether such
      connectivity in the working memory and default mode networks is modulated by
      changes in cognitive load. Functional connectivity was measured in a steady-state
      verbal identity N-back task for three different conditions (N = 1, 2, and 3) as
      well as in the resting state. We found that as cognitive load increases, the
      functional connectivity within both the working memory the default mode network
      increases. To test whether functional connectivity between the working memory and
      the default mode networks changed, we constructed maps of functional connectivity
      to the working memory network as a whole and found that increasingly negative
      correlations emerged in a dorsal region of the posterior cingulate cortex. These
      results provide further evidence that low frequency fluctuations in BOLD signals
      reflect variations in neural activity and suggests interaction between the
      default mode network and other cognitive networks.

PMID- 21077137
TI  - Spatial patterns of intrinsic brain activity in mild cognitive impairment and
      Alzheimer's disease: a resting-state functional MRI study.
AB  - We used resting-state functional MRI to investigate spatial patterns of
      spontaneous brain activity in 22 healthy elderly subjects, as well as 16 mild
      cognitive impairment (MCI) and 16 Alzheimer's disease (AD) patients. The pattern
      of intrinsic brain activity was measured by examining the amplitude of low
      frequency fluctuations (ALFF) of blood oxygen level dependent signal during rest.
      There were widespread ALFF differences among the three groups throughout the
      frontal, temporal, and parietal cortices. Both AD and MCI patients showed
      decreased activity mainly in the medial parietal lobe region and lentiform
      nucleus, while there was increased activity in the lateral temporal regions and
      superior frontal and parietal regions as compared with controls. Compared with
      MCI, the AD patients showed decreased activity in the medial prefrontal cortex
      and increased activity in the superior frontal gyrus and inferior and superior
      temporal gyri. Specifically, the most significant ALFF differences among the
      groups appeared in the posterior cingulate cortex, with a reduced pattern of
      activity when comparing healthy controls, MCI, and AD patients. Additionally, we
      also showed that the regions with ALFF changes had significant correlations with
      the cognitive performance of patients as measured by mini-mental state
      examination scores. Finally, while taking gray matter volume as covariates, the
      ALFF results were approximately consistent with those without gray matter
      correction, implying that the functional analysis could not be explained by
      regional atrophy. Together, our results demonstrate that there is a specific
      pattern of ALFF in AD and MCI, thus providing insights into biological mechanisms
      of the diseases.

PMID- 21077146
TI  - Contribution of the primary motor cortex to motor imagery: a subthreshold TMS
      study.
AB  - Motor imagery (MI) mostly activates the same brain regions as movement execution
      (ME) including the primary motor cortex (Brodmann area 4, BA4). However, whether
      BA4 is functionally relevant for MI remains controversial. The finding that MI
      tasks are impaired by BA4 virtual lesions induced by transcranial magnetic
      stimulation (TMS) supports this view, though previous studies do not permit to
      exclude that BA4 is also involved in other processes such as hand recognition.
      Additionally, previous works largely underestimated the possible negative
      consequences of TMS-induced muscle twitches on MI task performance. Here we
      investigated the role of BA4 in MI by interfering with the function of the left
      or right BA4 in healthy subjects performing a MI task in which they had to make
      laterality judgements on rotated hand drawings. We used a subthreshold repetitive
      TMS protocol and monitored electromyographic activity to exclude undesirable
      effects of hand muscle twitches. We found that BA4 virtual lesions selectively
      increased reaction times in laterality judgments on hand drawings, leaving
      unaffected a task of equal difficulty, involving judgments on letters.
      Interestingly, the effects of virtual lesions of left and right BA4 on MI task
      performance were the same irrespective of the laterality (left/right) of hand
      drawings. A second experiment allowed us to rule out the possibility that BA4
      lesions affect visual or semantic processing of hand drawings. Altogether, these
      results indicate that BA4 contribution to MI tasks is specifically related to the
      mental simulation process and further emphasize the functional coupling between
      ME and MI.

PMID- 21077147
TI  - Altered functional adaptation to attention and working memory tasks with
      increasing complexity in relapsing-remitting multiple sclerosis patients.
AB  - As attention, processing speed, and working memory seem to be fundamental for a
      broad range of cognitive performance, the present study on patients with mild
      forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains.
      To explore subtle neuropsychological changes in either the clinical or fMRI
      domain, we applied a multistep experimental design with increasing task
      complexity to investigate global brain activity, functional adaptation, and
      behavioral responses to typical cognitive processes related to attention and
      working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9
      females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded
      Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive
      impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50
      years, 6 women) participated. After a comprehensive neuropsychological
      assessment, participants performed different fMRI experiments testing attention
      and working memory. In the neuropsychological assessment, patients showed only
      subtle reduction in learning and memory abilities. In the fMRI experiments, both
      groups activated the brain areas typically involved in attention and working
      memory. HC showed a linear in- or decrease in activation paralleling the changing
      task complexity. Patients showed stronger activation change at the level of the
      simple tasks and a subsequent saturation effect of (de-)activation at the highest
      task load. These group/task interaction differences were found in the right
      parahippocampal cortex and in the middle and medial frontal regions. Our results
      indicate that, in MS, functional adaptation patterns can be found which precede
      clinical evidence of apparent cognitive decline.

PMID- 21077148
TI  - Arabidopsis thaliana resistance to insects, mediated by an earthworm-produced
      organic soil amendment.
AB  - BACKGROUND: Vermicompost is an organic soil amendment produced by earthworm
      digestion of organic waste. Studies show that plants grown in soil amended with
      vermicompost grow faster, are more productive and are less susceptible to a
      number of arthropod pests. In light of these studies, the present study was
      designed to determine the type of insect resistance (antixenosis or antibiosis)
      present in plants grown in vermicompost-amended potting soil. Additionally, the
      potential role of microarthropods, entomopathogenic organisms and non-pathogenic
      microbial flora found in vermicompost on insect resistance induction was
      investigated. RESULTS: Findings show that vermicompost from two different sources
      (Raleigh, North Carolina, and Portland, Oregon) were both effective in causing
      Arabidopsis plants to be resistant to the generalist herbivore Helicoverpa zea
      (Boddie). However, while the Raleigh (Ral) vermicompost plant resistance was
      expressed as both non-preference (antixenosis) and milder (lower weight and
      slower development) toxic effect (antibiosis) resistance, Oregon (OSC)
      vermicompost plant resistance was expressed as acute antibiosis, resulting in
      lower weights and higher mortality rates. CONCLUSION: Vermicompost causes plants
      to have non-preference (antixenosis) and toxic (antibiosis) effects on insects.
      This resistance affects insect development and survival on plants grown in
      vermicompost-amended soil. Microarthropods and entomopathogens do not appear to
      have a role in the resistance, but it is likely that resistance is due to
      interactions between the microbial communities in vermicompost with plant roots,
      as is evident from vermicompost sterilization assays conducted in this study.

PMID- 21077156
TI  - Clinical implications of intra- and interobserver reproducibility of transvaginal
      sonographic measurement of gestational sac and crown-rump length at 6-9 weeks'
      gestation.
AB  - OBJECTIVES: To assess intra- and interobserver agreement of routinely performed
      measurements-crown-rump length (CRL) and mean gestational sac diameter (MSD)-for
      assessing the likelihood of miscarriage in the first trimester of pregnancy using
      transvaginal sonography. METHODS: A cross-sectional study of CRL and gestational
      sac measurements in first-trimester pregnancies was conducted in a fetal medicine
      referral center with a predominantly Caucasian population. Gestational age ranged
      from 6 to 9 weeks. All patients underwent a transvaginal ultrasound examination
      using a high-resolution ultrasound machine. Two measurements of CRL and
      measurements of three diameters of the gestational sac were obtained by two
      observers. Agreement within and between observers for CRL and between observers
      for MSD was analyzed using 95% prediction intervals, Bland-Altman plots with 95%
      limits of agreement and the intraclass correlation coefficient (ICC). RESULTS: In
      total 54 patients were included in the study, with measurements obtained by both
      observers in 44 of these. Intra- and interobserver ICCs were high for CRL
      measurements, with values of 0.992 and 0.993 for intraobserver agreement and
      0.993 for interobserver agreement. For the MSD, the interobserver ICC was 0.952.
      Limits of agreement were +/- 8.91 and +/- 11.37% for intraobserver agreement of
      CRL and +/- 14.64% for interobserver agreement of CRL. For MSD, the interobserver
      limits of agreement were +/- 18.78%. For an MSD measurement of 20 mm by the first
      observer, the prediction interval for the second observer was 16.8-24.5 mm. For a
      CRL measurement of 6 mm, the prediction interval for the second observer was 5.4
      6.7 mm. CONCLUSION: For dating purposes, there is reasonable reproducibility of
      CRL measurements using transvaginal ultrasonography at 6-9 weeks' gestation. When
      diagnosing miscarriage based on measurements of CRL care must be taken for values
      close to any decision boundary. The higher interobserver variability that we
      observed for MSD has implications for the diagnosis of miscarriage based on this
      measurement in the absence of a visible embryo or yolk sac.

PMID- 21077157
TI  - Simultaneous real-time imaging of four-chamber and left ventricular outflow tract
      views using xPlane imaging capability of a matrix array probe.
AB  - OBJECTIVES: To determine the feasibility and reliability of using xPlane imaging
      to examine simultaneously the four-chamber and left ventricular outflow tract
      (LVOT) views in real time, to assess rotation angles from the four-chamber view
      to the LVOT view, and to investigate factors affecting the angles. METHODS: In
      145 fetuses at 11-37 weeks' gestation, we visualized the four-chamber view in one
      of three cardiac positions: a subcostal view with the apex at the 3 or 9 o'clock
      position; an apical view with the apex at the 12 or 6 o'clock position; or a view
      with the fetal heart apex midway between these two positions. We then used the
      rotation function of xPlane imaging, using the four-chamber view as the reference
      plane, to visualize the LVOT view simultaneously in real time on the secondary
      image plane, on the right side of the split screen, by rotating a reference line
      from 0 degrees  with a rotation step of 5 degrees . The rotation angle necessary
      for the first appearance of LVOT was recorded as the first rotation angle. The
      reference line was then rotated until the LVOT was just out of view, and this
      last rotation angle was recorded as the second rotation angle. The difference
      between these two angles was recorded as the angle span of the LVOT display.
      Reliability was assessed by intraclass correlation coefficient (ICC). RESULTS: Of
      the 145 fetuses examined, 29 had cardiac defects. Using xPlane imaging, the LVOT
      was visualized successfully after 14 weeks in 95.1% of cases. The first and
      second rotation angles varied significantly with cardiac position (P < 0.001);
      when the fetal heart was examined using a subcostal approach with the apex at the
      3 or 9 o'clock position, the first rotation angle was smaller than that at the
      apical view for normal hearts (20 degrees  vs. 50 degrees , P < 0.001). There was
      also a significant difference for the second rotation angle and for the angle
      span, between fetuses with and without normal LVOT (P = 0.038 and 0.006,
      respectively). Regarding intra- and interobserver reliability for measurement of
      first and second rotation angles, the ICCs were high (range, 0.847-0.980).
      CONCLUSION: Using xPlane imaging, it is feasible to examine simultaneously the
      four-chamber and LVOT views in real time, and measurement of the rotation angles
      between these two views is reproducible. The rotation angles depend on the
      position of the fetal heart, and the normality of the LVOT. Proposed algorithms
      for examination of the fetal heart with three-/four-dimensional ultrasonography
      may need to be adapted to optimize visualization of the standard planes.

PMID- 21077158
TI  - MicroRNA miR-196a controls melanoma-associated genes by regulating HOX-C8
      expression.
AB  - Resulting from a screening for microRNAs differentially regulated in melanocytes
      and melanoma cells, we found expression of miR-196a to be significantly down
      regulated in malignant melanoma cell lines and tissue samples. As it was stated
      before that miR-196a might negatively regulate expression of the transcription
      factor HOX-C8, we analyzed HOX-C8 levels in NHEMs and melanoma cells and found a
      strong up-regulation of HOX-C8 expression in malignant melanoma cell lines and
      tissue samples compared with melanocytes. Several HOX-C8 target genes are known
      to be involved in processes such as oncogenesis, cell adhesion, proliferation and
      apoptosis. We, therefore, aimed to further investigate a potential "miR-196a ->
      HOX-C8 -> HOX-C8 target gene" relationship. Stable transfection with an miR-196a
      expression plasmid led to strong down-regulation of HOX-C8 expression in melanoma
      cells. Luciferase assays using reporter plasmids containing different fragments
      of the HOX-C8 3'UTR confirmed direct interactions of miR-196a with the HOX-C8
      mRNA. Focusing on target genes of HOX-C8, which might play an important role in
      melanomagenesis, we identified three genes (cadherin-11, calponin-1 and
      osteopontin) that are up- or down-regulated, respectively, by altered HOX-C8
      expression in miR-196a expressing cell clones and are thus indirectly regulated
      by this microRNA. As those target genes are closely related to important cellular
      mechanisms such as cell adhesion, cytoskeleton remodeling, tumor formation and
      invasive behavior of tumor cells, altered miR-196a expression exerts strong
      effects contributing to tumor cell transformation and formation and progression
      of malignant melanoma. This fact is underlined by a strongly reduced invasive
      behavior of melanoma cells re-expressing miR-196a in vitro.

PMID- 21077160
TI  - In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA' in a
      human acute myeloid leukemia xenograft tumor model.
AB  - Target-specific acute myeloid leukemia (AML) immunotherapy requires selective
      cell-surface antigens on AML blast cells. CD64 is a promising candidate antigen
      because it is abundantly expressed on monocytoid differentiated AML subtypes. In
      previous studies, a chemically linked full-length anti-CD64 immunotoxin based on
      ricin A showed promising results in several animal models, but further
      development has been hindered by its substantial, dose-limiting off-target
      effects. We recently constructed the recombinant immunotoxin H22(scFv)-ETA',
      comprising a truncated Pseudomonas exotoxin A (PE) and a humanized scFv antibody
      against CD64. This molecule was shown to kill CD64(+) AML-derived tumor cell
      lines and primary patient-derived AML cells specifically, both in vitro and ex
      vivo. Here we describe the in vivo efficiency of H22(scFv)-ETA' in the U937/SCID
      mouse xenograft model for human AML, by providing immunohistochemical evidence
      for the elimination of human CD64(+) tumor cells in mouse organs. H22(scFv)-ETA'
      showed potent antitumor activity against myeloid tumor cells and significantly
      prolonged the overall survival of AML xenograft animals. In conclusion, H22(scFv)
      ETA' is efficacious against AML with monocytoid differentiation in vitro and in
      animal models in vivo, providing the basis for a novel therapeutic strategy for
      the treatment of AML patients.

PMID- 21077170
TI  - Regional and zonal histo-morphological characteristics of the lapine menisci.
AB  - The menisci have crucial weight-bearing roles in the knee. Regional variations in
      structure and cellularity of the meniscus have only been minimally investigated.
      Therefore, the goal of this study was to illustrate the regional cell density,
      tissue area, and structure of healthy lapine menisci. Skeletally mature Flemish
      Giant rabbits were used for this study. Upon sacrifice, menisci were removed,
      fixed in formalin, and cryosectioned. Histological analysis was performed for the
      detection of sulfated glycosaminoglycans (GAG), collagen Types I and II, cellular
      density, and tissue area. ANOVA and paired t tests were used for testing of
      statistical significance. Glycosaminoglycan coverage of the medial meniscus
      significantly varied between regions, with the anterior region demonstrating
      significantly more GAG coverage than the posterior region. Inter- and intra
      meniscal comparisons revealed variations between zones, with trends that outer
      zones of the medial menisci had less GAG coverage. Collagen Types I and II had
      marked characteristics and varying degrees of coverage across regions. Tissue
      area varied between regions for both medial and lateral menisci. Cellular density
      was dependent on region in the lateral meniscus. This is the first study to
      illustrate regional and zonal variation in glycosaminoglycan coverage, size, and
      cellular density for healthy lapine meniscal tissue. This data provides baseline
      information for future investigations in meniscal injury models in rabbits.

PMID- 21077171
TI  - A neurological comparative study of the harp seal (Pagophilus groenlandicus) and
      harbor porpoise (Phocoena phocoena) brain.
AB  - The cetacean brain is well studied. However, few comparisons have been done with
      other marine mammals. In this study, we compared the harp seal (Pagophilus
      groenlandicus) and the harbor porpoise brain (Phocoena phocoena). Stereological
      methods were applied to compare three areas of interest: the entire neocortex and
      two subdivisions of the neocortex, the auditory and visual cortices. The total
      number of neurons and glial cells in the three regions was estimated. The main
      results showed that the harbor porpoise have an estimated 14.9 * 10(9)
      neocortical neurons and 34.8 * 10(9) neocortical glial cells, whereas the harp
      seal have 6.1 * 10(9) neocortical neurons and 17.5 * 10(9) neocortical glial
      cells. The harbor porpoise have significantly more neurons and glial cells in the
      auditory cortex than in the visual cortex, whereas the pattern was opposite for
      the harp seal. These results are the first to provide estimates of the number of
      neurons and glial cells in the neocortex of the harp seal and harbor porpoise
      brain and offer new data to the comparative field of mammalian brain evolution.

PMID- 21077176
TI  - A method to calculate the volume of palatine tonsils.
AB  - The purpose of this study was to obtain a mathematical formula to calculate the
      tonsillar volume out of its measurements assessed on surgical specimens. Thirty
      consecutive surgical specimens of pediatric tonsils were studied. The maximum
      lengths ("a"), widths ("b"), and depths ("c") of the dissected specimens were
      measured in millimeters, and the volume of each tonsil was measured in
      milliliters. One-sample Kolmogorov-Smirnov test was used to check the normality
      of the sample. To calculate the reproducibility of the quantitative variables,
      intraclass correlation coefficients were used. Two formulas with high
      reproducibility (coefficient R between 0.75 and 1) were obtained: 1) [a*b*c*
      0.5236] with R = 0.8688; and 2) [a*b*b* 0.3428] with R = 0.9073. It is possible
      to calculate the volume of the palatine tonsils in surgical specimens precisely
      enough based on their three measures, or their two main measures (length and
      width).

PMID- 21077177
TI  - Extracellular-superoxide dismutase expression during monocytic differentiation of
      U937 cells.
AB  - Leukemic cell lines, such as U937, THP-1, and HL60 cells, can differentiate into
      macrophages following exposure to various agents including 12-O
      tetradecanoylphorbol-13-acetate (TPA) in vitro. It is well known that TPA
      enhances reactive oxygen species (ROS) generation through the activation of NADPH
      oxidase (NOX), and ROS act as mediators in TPA signaling. Extracellular
      superoxide dismutase (EC-SOD) is a major anti-oxidative enzyme that protects the
      cells from damaging effects of superoxide. Recently, the reduction of Cu/Zn-SOD
      and the induction of Mn-SOD by TPA in leukemic cells have been reported; however,
      the regulation of EC-SOD by TPA remains poorly understood. Here, we explored the
      regulation of EC-SOD during the monocytic differentiation of U937 cells by TPA.
      We observed the reduction of EC-SOD and Cu/Zn-SOD, whereas the induction of Mn
      SOD during the differentiation of U937 cells. The reduction of EC-SOD and Cu/Zn
      SOD was attenuated by pretreatments with GF109203X (an inhibitor of protein
      kinase C, PKC), diphenyleneiodonium (an inhibitor of NOX), and U0126 (an
      inhibitor of mitogen-activated protein kinase kinase, MEK/extracellular-signal
      regulated kinase, ERK). Interestingly, pretreatment with BAY11-7082 (an inhibitor
      of nuclear factor-kappaB, NF-kappaB) suppressed the reduction of Cu/Zn-SOD, but
      not of EC-SOD. Furthermore, we also determined the involvement of newly
      synthesized protein and the instability of mRNA in the reduction of EC-SOD.
      Overall, our results suggest that the expression of EC-SOD is decreased by TPA
      through intracellular signaling consisting of PKC, NOX-derived ROS and MEK/ERK,
      but not of NF-kappaB signaling.

PMID- 21077186
TI  - Outcomes after the use of gastrostomy tubes in patients whose head and neck
      cancer was managed with radiation therapy.
AB  - BACKGROUND: The purpose of this study was to examine the effect of continued oral
      intake and duration of gastrostomy tube placement on posttreatment nutritional
      outcomes in patients being irradiated for head and neck cancer. METHODS: Factors
      associated with continued oral intake and its association with posttreatment
      outcomes were analyzed. RESULTS: Patients with no oral intake (39.6% of 91) were
      more likely to have laryngeal tumors, advanced disease, and pretreatment
      gastrostomy tube placement. Of the 55 patients whose gastrostomy tubes had been
      removed, those with continued oral intake and shorter gastrostomy tube placement
      were more likely to maintain their weight and report eating scores in the higher
      functioning category, but have more restricted diets. Observed survival was
      significantly better for the continued-oral-intake group (p = .001). CONCLUSION:
      The beneficial effects of continued oral intake and shorter gastrostomy tube
      placement on posttreatment outcomes shown in this study suggest that clinicians
      involved in these patients' care should emphasize oral intake during treatment.

PMID- 21077189
TI  - Probing nanotribological and electrical properties of organic molecular films
      with atomic force microscopy.
AB  - Structural aspects of organic molecular films, such as disordering, packing
      density, molecular bending or tilts, and phase separation, influence electrical
      properties as well as friction and adhesion. This indicates a correlation between
      nanomechanical and charge transport properties of molecular films at the
      molecular scale. In this review, we highlight the recent studies on correlations
      between charge transport and nanomechanical properties probed with atomic force
      microscopy. We discuss the key issues that determine charge transport and
      nanomechanical properties on several organic molecular films, including self
      assembled monolayers formed by saturated hydrocarbon molecules conjugated
      molecules, and hybrid molecules as well as polymer and polymer blend films. We
      address the role of molecular deformation and bending in friction and conductance
      measurements.

PMID- 21077202
TI  - Genotype-phenotype correlation in DTDST dysplasias: Atelosteogenesis type II and
      diastrophic dysplasia variant in one family.
AB  - Mutations in diastrophic dysplasia sulfate transporter (DTDST) cause a spectrum
      of autosomal recessive chondrodysplasias. In decreasing order of severity, they
      include processes designated as achondrogenesis type IB (ACG-1B),
      atelosteogenesis type II (AO2), diastrophic dysplasia (DTD), diastrophic
      dysplasia variant (DTDv), and recessively inherited multiple epiphyseal dysplasia
      (rMED). This is the first report of an extended family with unequivocally
      distinct phenotypes on the DTDST spectrum. Two siblings have DTDv and their first
      cousin had AO2. They all share the common Finnish mutation (IVS1 + 2C>T). The two
      patients with DTDv have the previously reported R279W extracellular domain
      missense mutation. The second mutation in the patient with AO2 is c.172delA, a
      deletion of one nucleotide causing a previously unreported frameshift mutation.
      This is the first published case of an individual with a frameshift mutation
      combined with the Finnish mutation. These three patients provide an opportunity,
      in concert with a review of previous literature, to further examine the genotype
      phenotype correlation of DTDST. Analysis suggests that, while the DTDST family of
      disorders contains at least seven different conditions, mutations in the DTDST
      gene, in fact, appear to cause a phenotypic continuum. Furthermore, DTDST
      genotype alone is an imperfect predictor of clinical severity along this
      continuum.

PMID- 21077203
TI  - Macrocephaly-capillary malformation: Analysis of 13 patients and review of the
      diagnostic criteria.
AB  - Macrocephaly-capillary malformation (M-CM) is a genetic syndrome of unknown
      etiology characterized by an enlarged head circumference and patchy, reticular
      capillary malformation. We describe the clinical features of 13 cases, report on
      the genome-wide Copy Number Variation characterization of these patients, analyze
      the main clinical features of this syndrome and propose a modification of the
      current diagnostic criteria: the inclusion of both overgrowth/asymmetry and
      neuroimaging alterations as major criteria.

PMID- 21077204
TI  - New intermediate phenotype between MED and DD caused by compound heterozygous
      mutations in the DTDST gene.
AB  - DTDST mutations cause a spectrum of diastrophic dysplasia disorders characterized
      by defects of proteoglycans sulfation. Reduction of sulfate/chloride antiporter
      activity is manifested by lower sulfate uptake and depends on a combination of
      mutations in DTDST. We analyzed a family with an autosomal recessive form of bone
      dysplasia. Three affected brothers from this family are compound heterozygotes
      for C653S/A715V mutations. We classified their phenotype as a new intermediate
      form between diastrophic dysplasia and multiple epiphyseal dysplasia, manifested
      by shortening of stature, metatarsus adductus/club foot, mild brachydactyly,
      proximally placed thumbs and clinodactyly of the fifth fingers. Radiographs
      document platyspondyly most marked in the lower thoracic and upper lumbar spine,
      epiphyseal dysplasia affecting predominantly the femoral heads, widening of the
      metaphyses, narrow growth cartilage and multilayered patellae. Exaggerated lesser
      trochanters of femur, that is, "monkey wrench" sign, elevated greater
      trochanters, thin upper pubic rami, grossly normal carpal/tarsal bones and
      severe, early onset osteoarthritis were other notable features.

PMID- 21077205
TI  - Brachydactyly type A1 with short humerus and associated skeletal features.
AB  - We report on a three-generation family affected with an osteochondrodysplasia
      transmitted as an autosomal dominant trait. The phenotype consists of short
      humerus, curved radius with accessory ossification centre at the proximal third
      of ulna, variable short stature and brachydactyly, and has not been reported to
      the best of our knowledge. The brachydactyly falls into the brachydactyly A1
      category (especially short 2nd, 4th, and 5th middle phalanges). A unique feature
      in one family member is triphalangeal thumbs. Vertebrae are normal. Mental
      development is normal and deafness is seen in some of the family members. A
      mutation was excluded by sequencing the entire coding regions of the IHH gene
      encoding the Indian Hedgehog protein and the GDF5 gene. This condition is a novel
      chondrodyplasia phenotype or possibly one end of the spectrum of the
      brachydactyly A1.

PMID- 21077206
TI  - The financing of clinical genetics research by disease advocacy organizations: A
      review of funding disclosures in biomedical journals.
AB  - Anecdotal reports suggest that disease-advocacy groups (DAOs) participate in
      multiple aspects of clinical research. No systemic analysis of the extent of DAO
      involvement in clinical genetics research has been conducted to date. We
      conducted a systematic review of journal articles published in 2004 and 2005
      reporting clinical research on 50 genetic diseases to assess the extent to which
      DAOs financed the studies reported, assisted in subject recruitment, or
      participated in other aspects of research. Of 513 articles, 350 (68%) included a
      statement regarding research support. Of these articles, 114 (33%) acknowledged
      DAO funding. The proportion of articles reporting financial support from a DAO
      varied greatly by disease. Articles reporting financial support from a DAO often
      identified at least one additional source of support (73%). Of the articles
      examined, 19 (4%) acknowledged DAO assistance with subject recruitment and 11
      (2%) included an author affiliated with a DAO. DAOs provide financial support for
      numerous clinical research studies in genetics, often in partnership with
      government agencies and for-profit corporations. DAOs also participate in other
      aspects of clinical research, including subject recruitment. Future studies
      should seek to characterize these research partnerships more fully.

PMID- 21077217
TI  - beta-Amino alcohol selectors for enantioselective separation of amino acids by
      ligand-exchange capillary zone electrophoresis in a low molecular weight
      organogel.
AB  - A new family of copper ligand-exchange selectors, L- or D-beta-amino alcohols, is
      employed for the chiral separation of D,L-dansyl-amino acids, unmodified amino
      acid racemates, phenylalanine and tryptophan, and beta-blocker L,D-propranolol by
      SDS-micellar electrokinetic chromatography and by electrophoretic chromatography
      in a low molecular weight organogel (LMOG)-filled capillary. The LMOG comprised a
      self-assembled fibrillar gel of trans-(1S,2S)-1,2-bis-(dodecylamido) cyclohexane
      in methanol. The di-L-valinol-copper complex exhibited the best performance on
      LMOG-CE compared with all other beta-amino alcohol-copper selectors. The
      dependence of chiral resolution on the pH*, the ratio between the copper and the
      L-valinol ligand and the concentration of added selector complex in the run
      buffer were investigated revealing a marked difference between the activity of
      the copper-valinol and the previously studied copper-valine selector. The optimal
      separation conditions were achieved using a 2:1 valinol/copper ratio, in
      accordance with the 2:1 structure of the complex, which was proven by single
      crystal and powder X-ray diffractions and by elemental analysis. Unlike the
      copper-valine selectors that could be used only under acidic conditions (pH*
      3.5), the copper-valinol selectors could be used under near-neutral conditions
      and even at pH* 9.1. A comparison between SDS-micellar electrokinetic
      chromatography and LMOG-CE under otherwise identical conditions revealed a
      significant superior separation on the LMOG-filled capillaries.

PMID- 21077218
TI  - Improved instrumentation for large-size two-dimensional protein maps.
AB  - Novel instrumentation for performing large-size (>25 cm) 2-D maps is reported
      here. To perform the first dimension, we developed a power supply that can
      deliver a voltage of up to 15,000 V and allows regulation of current (up to 200
      MUA) onto each individual focusing IPG strip. The IEF strip tray can accommodate
      up to 12 IPG strips and the electrodes slide on a ruler, thus permitting running
      strips of any length up to 45 cm. In addition, this apparatus also includes a
      second power supply that allows the performance of electrophoresis at high
      amperage (400 mA) and a Peltier system that allows a 10-80 degrees C temperature
      control.

PMID- 21077219
TI  - Polyacrylamide grafted on multi-walled carbon nanotubes for open-tubular
      capillary electrochromatography: comparison with silica hydride and polyacrylate
      phase matrices.
AB  - A new nanoparticle-bound polymer stationary phase was prepared by in situ
      polymerization of methacrylamide (MAA), bis-acrylamide crosslinker, and
      carboxylated multi-walled carbon nanotubes (multi-walled CNTs; MWNTs), using the
      abundant double bonds in the cyclopentadienyl rings in MWNT structure, on a
      silanized capillary. Each intermediate capillary between the synthesis steps was
      characterized by SEM, by ATR-IR, and by EOF measurements varying the pH,
      concentration, and volumetric ratios of ACN in running buffers. The resulting EOF
      profile was comparable to those of two other capillaries with different phase
      matrices, silica hydride and polybutyl methacrylate (BMA) phases. With the
      complex functionality of MWNTs on the hydrophilic polyacrylamide network, the MAA
      CNT capillary was capable of separating diverse samples with a wide range of
      polarity and dissociation properties using open-tubular CEC. Besides optimizing
      CEC conditions, the migration times of samples were analyzed with respect to
      velocity and retention factors to evaluate electrophoretic and chromatographic
      contributions to the CEC mechanism. The migration rates of benzoic acids were
      determined by the electrophoretic mobilities of the various phenolate ions, while
      phenolic aldehydes and ketones were additionally influenced by chromatographic
      interactions, such as pi-pi, electrostatic effects, hydrogen bonding, and
      hydrophobic interactions. The retention factors were greater for flavonoids,
      which are polyphenolic, than for simple phenols, but were smaller than those
      obtained from the hydrophobic BMA-CNT column. A complete well-resolved separation
      of the cationic forms of tetracyclines was acheived either by electrophoresis or
      by chromatography in the MAA-CNT capillary, but not in the BMA-CNT and silica
      hydride-CNT capillaries.

PMID- 21077223
TI  - The shortest metal-metal bond.
AB  - The synthesis and isolation of stable bimetallic complexes that contain formally
      quintuply bonded transition metals is a novel and emerging field of science.
      Efforts have been undertaken in designing and tuning the ligands to achieve a
      very short (actually the shortest) metal-metal bond. The motivation for these
      efforts arose from the expectation that an increasing bond order may go along
      with a shortening of the bond length. In consequence, formally quintuply bonded
      bimetallics could have shorter metal-metal distances than quadruply bonded ones.
      A chromium homo-bimetallic complex with a Cr-Cr bond length of 1.7293(12) A has
      been synthesized, and a formal bond order of five was assigned. This compound
      holds the record for the shortest metal-metal bond in a stable molecule to date.
      At this stage, there is no evidence that additional shortening is impossible.

PMID- 21077224
TI  - Synthesis of water soluble, biodegradable, and electroactive polysaccharide
      crosslinker with aldehyde and carboxylic groups for biomedical applications.
AB  - We report the synthesis and characterization of a polysaccharide crosslinker of
      tetraaniline grafting oxidized sodium alginate with large aldehyde and carboxylic
      groups. We demonstrate that this copolymer has the following properties: it is
      water soluble under any pH, biodegradable, electroactive, and noncytotoxic; it
      can self-assemble into nanoparticles with large active functional groups on the
      outer surface; it can crosslink materials with amino and aminoderivative groups
      like gelatin to form hydrogels, and thus the electroactivity is readily
      introduced to the materials. This copolymer has potential applications in
      biomedical fields such as tissue engineering, drug delivery, and nerve probes
      where electroactivity is required.

PMID- 21077225
TI  - Multi-featured macroporous agarose-alginate cryogel: synthesis and
      characterization for bioengineering applications.
AB  - In this study agarose-alginate scaffolds are synthesized using cryogelation
      technology in different formats like monolith, sheet, discs, and beads, and show
      amiable mechanical strength like soft tissue properties and high interconnected
      macroporous degradable architecture. In cell-material interactions, fibroblast
      (NIH-3T3) cells showed good adherence and proliferation on these scaffolds
      presenting its potential application in soft tissue engineering. The application
      of cryogel beads and monoliths was also examined by the efficient immobilization
      of bacterial cells (BL21) on these matrices revealing their use for recovery of
      product from continuous fermentation systems without cell leakage. These
      scaffolds also showed potential as a filter for repeated recovery of heavy metal
      binding, such as copper and nickel from the waste water. The cryogels prepared
      herein do have a number of unique features that make them an important class of
      soft materials for developing multi-featured scaffolds as a novel carrier for
      bioengineering applications.

PMID- 21077226
TI  - An optimized RGD-decorated micellar drug delivery system for albendazole for the
      treatment of ovarian cancer: from RAFT polymer synthesis to cellular uptake.
AB  - Block copolymers were prepared via RAFT polymerization with P(PEGMEMA) as the
      hydrophilic block to form micelles for the controlled delivery of ABZ. The group
      contribution method was used to estimate the partial solubility parameters for
      ABZ and various polymers as potential core-forming block to achieve optimum
      compatibility. Different ratios between MMA and LMA, a non-compatible monomer,
      were prepared. Cytotoxicity tests revealed a high toxicity of the ABZ-loaded
      micelle resulting in 80% cell deaths at a micelle concentration of 10 ug . mL(-1)
      . Cellular uptake of micelles has been studied using fluorescently labeled
      micelles, showing that a large fraction of micelles is readily taken up by OVCAR
      3 cells. RGD-conjugated micelles were prepared and showed an increased cellular
      uptake.

PMID- 21077227
TI  - Polyurethane/dermatan sulfate copolymers as hemocompatible, non-biofouling
      materials.
AB  - The range of application of polyurethanes has been limited by their poor
      hemocompatibility and inability to resist non-specific binding of biomolecules
      and cells. In this work, a non-adhesive PU-based material was synthesized via the
      copolymerization of PU with dermatan sulfate. Incorporation of DS into the PU
      backbone dramatically increased material hydrophilicity and decreased protein
      adsorption. The in vitro adhesion of several cell types, including platelets,
      also significantly decreased with increasing DS content. Both the physical and
      biological properties of the DS contributed to the anti-adhesive properties of
      the PU/DS copolymer, and this anti-adhesive nature of PU/DS renders this new
      biomaterial attractive for blood-contacting or non-fouling applications.

PMID- 21077233
TI  - Miniaturization 2010.

PMID- 21077234
TI  - Electrothermal flow effects in insulating (electrodeless) dielectrophoresis
      systems.
AB  - We simulate electrothermally induced flow in polymeric, insulator-based
      dielectrophoresis (iDEP) systems with DC-offset, AC electric fields at finite
      thermal Peclet number, and we identify key regimes where electrothermal (ET)
      effects enhance particle deflection and trapping. We study a single, two
      dimensional constriction in channel depth with parametric variations in electric
      field, channel geometry, fluid conductivity, particle electrophoretic (EP)
      mobility, and channel electroosmotic (EO) mobility. We report the effects of
      increasing particle EP mobility, channel EO mobility, and AC and DC field
      magnitudes on the mean constriction temperature and particle behavior.
      Specifically, we quantify particle deflection and trapping, referring to the
      deviation of particles from their pathlines due to dielectrophoresis as they pass
      a constriction and the stagnation of particles due to negative dielectrophoresis
      near a constriction, respectively. This work includes the coupling between fluid,
      heat, and electromagnetic phenomena via temperature-dependent physical
      parameters. Results indicate that the temperature distribution depends strongly
      on the fluid conductivity and electric field magnitude, and particle deflection
      and trapping depend strongly on the channel geometry. Electrothermal (ET) effects
      perturb the EO flow field, creating vorticity near the channel constriction and
      enhancing the deflection and trapping effects. ET effects alter particle
      deflection and trapping responses in insulator-based dielectrophoresis devices,
      especially at intermediate device aspect ratios (2 <= r <= 7) in solutions of
      higher conductivity (sigma m >= 1 * 10(-3)S/m). The impact of ET effects on
      particle deflection and trapping are diminished when particle EP mobility or
      channel EO mobility is high. In almost all cases, ET effects enhance negative
      dielectrophoretic particle deflection and trapping phenomena.

PMID- 21077228
TI  - Effect of a scaffold fabricated thermally from acetylated PLGA on the formation
      of engineered cartilage.
AB  - A MHDS has been employed to fabricate 3D scaffolds from PLGA with acetyl
      endgroups to achieve in vivo regeneration of cartilage tissue. The fabricated
      acetylated-PLGA scaffold showed open pores and interconnected structures. Rabbit
      chondrocytes were seeded on the PLGA scaffolds and transplanted immediately into
      subcutaneous sites of athymic mice. Chondrocytes transplantation with untreated
      PLGA scaffolds served as a control. Histological analysis of the implants at 4
      weeks with H&E staining and alcian blue staining revealed higher extracellular
      matrix and GAG expression at the neocartilage in the PLGA-6Ac scaffolds than that
      of the PLGA-6OH scaffold group. This endgroup-modified scaffold may be useful for
      successful cartilage tissue engineering in orthopedic applications.

PMID- 21077236
TI  - Step width, spacing, and resolution in gradient elution moving boundary
      electrophoresis. Part 1. Theory and comparison with zone electrophoresis.
AB  - Gradient elution moving boundary electrophoresis (GEMBE) is a recently described
      technique for electrophoretic separations in short capillaries or microchannels.
      With GEMBE, the electrophoretic migration of analytes is opposed by a bulk
      counterflow of separation buffer. The counterflow velocity is varied over the
      course of a separation so that analytes with different mobilities enter the
      separation channel at different times and are detected as moving boundary, step
      wise increases in the detector response. The resolution of a GEMBE separation is
      thus dependent on the rate at which the counterflow velocity is varied, and
      relatively high-resolution separations can be performed with short microfluidic
      channels or capillaries. In this paper, a theoretical description of GEMBE is
      presented that can be used for calculation of expected resolution and for
      optimization of GEMBE separations. A comparison is made with CZE, a conventional
      electrophoretic separation technique for which the theoretical understanding is
      mature. The results indicate that the electric field strength and separation
      channel length are important parameters for both CZE and GEMBE. However, with
      GEMBE, the counterflow acceleration is also available as a parameter that can be
      easily adjusted for optimization of the trade-off between resolution and
      separation time. This allows for optimization of GEMBE separations by making
      changes only to the software controlling the apparatus rather than to the
      hardware of the apparatus itself. Further comparison of the theoretical
      descriptions of GEMBE and CZE indicates that the time required to achieve a
      desired resolution is equivalent for the two techniques.

PMID- 21077235
TI  - Characterization of particle capture in a sawtooth patterned insulating
      electrokinetic microfluidic device.
AB  - Here we present a scheme to separate particles according to their characteristic
      physical properties, including size, charge, polarizability, deformability,
      surface charge mobility, dielectric features, and local capacitance. Separation
      is accomplished using a microdevice based on direct current insulator gradient
      dielectrophoresis that can isolate and concentrate multiple analytes
      simultaneously at different positions. The device is dependent upon
      dielectrophoretic and electrokinetic forces incorporating a global longitudinal
      direct current field as well as using shaped insulating features within the
      channel to induce local gradients. This design allows for the production of
      strong local field gradients along a global field causing particles to enter,
      initially transported through the channel by electrophoresis and electroosmosis
      (electrokinetics), and to be isolated via repulsive dielectrophoretic forces that
      are proportional to an exponent of the field gradient. Sulfate-capped polystyrene
      nano and microparticles (20, 200 nm, and 1 MUm) were used as probes to
      demonstrate the influence of channel geometry and applied longitudinal field on
      separation behavior. These results are consistent with models using similar
      channel geometry and indicate that specific particulate species can be isolated
      within a distinct portion of the device, whereas concentrating particles by
      factors from 10(3) to 10(6).

PMID- 21077237
TI  - Step width, spacing, and resolution in gradient elution moving boundary
      electrophoresis. Part 2. Results from experiment.
AB  - In Part 1 of this work, a theoretical description of gradient elution moving
      boundary electrophoresis (GEMBE) is presented along with a comparison between
      GEMBE and the more conventional technique of CZE. In this second part,
      experimental results are presented for comparison with the theoretical
      predictions of Part 1. Results for the step width, spacing, and resolution are
      examined as a function of the salient parameters affecting the results of a GEMBE
      separation (starting pressure, counterflow acceleration, and electric field
      strength).

PMID- 21077238
TI  - Novel shape and placement definitions with retention modeling for solid
      microfabricated pillar columns for CEC and HPLC.
AB  - A novel design approach for optimizing the shape of microfabricated pillar
      columns for LC is presented. 2-D flow simulations are performed with a focus on
      electrokinetically driven flow, in order to evaluate the performance of the new
      method. The proposed foil shape is compared with geometrical shapes known from
      the literature, for various arrangements. It yields a much more uniform velocity
      field distribution and a decrease in plate height values up to 25%. In addition
      to shape optimization, a new method for spatial arrangement of structures is
      presented. With the aim of conserving the hydrodynamic balance, the axial spacing
      of the pillars is adjusted according to the proposed equivalent width approach.
      When compared with a fixed interpillar spacing in all directions, it increases
      the flow uniformity and results in an 18% lower plate height. A new direct
      simulation approach is implemented to model both flow field and retention for
      solid microfabricated pillar structures in the 2-D domain. This model, which
      defines retention as inward/outward fluxes through the wall surfaces as first
      order reactions, enables monitoring of the time-dependent process and an
      evaluation of the parameters affecting performance. The meaning of the obtained
      results in a practical setting, with limitations in photolithography and
      microfabrication, will be highlighted.

PMID- 21077239
TI  - Microchip electroseparation of proteins using lipid-based nanoparticles.
AB  - Porous liquid crystalline lipid-based nanoparticles are shown here to enable
      protein analysis in microchip electroseparation by reducing sample adsorption.
      Additionally, higher stability and reproducibility of the separations were
      observed. The method was tested by separating green fluorescent protein (GFP) in
      hot embossed cyclic olefin polymer microchips with integrated fiber grooves for
      LIF detection. The sample adsorption was indirectly quantified by measuring the
      height, width and asymmetry of the separation peaks for various concentrations of
      nanoparticles in the sample and background electrolyte. Without nanoparticles,
      electropherograms displayed typical signs of extensive adsorption to the channel
      walls, with low, broad tailing peaks. Higher, narrower more symmetric peaks were
      generated when 0.5-10% nanoparticles were added, showing a dramatic reduction of
      sample adsorption. The current through the separation channel decreased with
      nanoparticle concentration, reducing to half its value when the nanoparticle
      concentration was increased from 0.5 to 4%. Addition of nanoparticles enabled
      separations that were otherwise hindered by extensive adsorption, e.g. separation
      of GFP mutants differing by only one amino acid. It was also observed that
      increasing the nanoparticle concentration increased the number of impurities that
      could be resolved in a GFP sample. This indicates that the adsorption is further
      reduced, and/or that the nanoparticles provide an interacting pseudostationary
      phase for electrochromatography.

PMID- 21077240
TI  - Pneumatic handling of droplets on-demand on a microfluidic device for seamless
      processing of reaction and electrophoretic separation.
AB  - Sequential operations of pre-separation reaction process by picoliter droplets
      and following electrophoretic separation process were realized in a single
      microfluidic device with pneumatic handling of liquid. The developed device
      consists of a fluidic chip made of PDMS, an electrode substrate, and a
      temperature control substrate on which thin film heater/sensor structures are
      fabricated. Liquid handling, including introduction of liquid samples, droplet
      generation, and merging of droplets, was implemented by pneumatic manipulation
      through microcapillary vent structures, allowing air to pass and stop liquid
      flow. Since the pneumatic manipulations are conducted in a fully automated manner
      by using a programmable air pressure control system, the user simply has to load
      liquid samples on each liquid port of the device. Droplets of 420 pL were
      generated with an accuracy of +/- 2 pL by applying droplet generation pressure in
      the range of 40-100 kPa. As a demonstration, a binding reaction of a 15 mer ssDNA
      with a peptide nucleic acid oligomer used as an oligoprobe followed by denaturing
      electrophoresis to discriminate a single-base substitution was performed within
      1.5 min. By exploiting the droplet-on-demand capability of the device, the
      influence of various factors, such as reaction time, mixing ratio and droplet
      configurations on the ssDNA-peptide nucleic acid binding reaction in the droplet
      based process, was studied toward realization of a rapid detection method to
      discriminate rapid single-base substitution.

PMID- 21077241
TI  - White LEDs as broad spectrum light sources for spectrophotometry: demonstration
      in the visible spectrum range in a diode-array spectrophotometric detector.
AB  - Although traditional lamps, such as deuterium lamps, are suitable for bench-top
      instrumentation, their compatibility with the requirements of modern miniaturized
      instrumentation is limited. This study investigates the option of utilizing solid
      state light source technology, namely white LEDs, as a broad band spectrum source
      for spectrophotometry. Several white light LEDs of both RGB and white phosphorus
      have been characterized in terms of their emission spectra and energy output and
      a white phosphorus Luxeon LED was then chosen for demonstration as a light source
      for visible-spectrum spectrophotometry conducted in CE. The Luxeon LED was fixed
      onto the base of a dismounted deuterium (D(2) ) lamp so that the light-emitting
      spot was geometrically positioned exactly where the light-emitting spot of the
      original D(2) lamp is placed. In this manner, the detector of a commercial CE
      instrument equipped with a DAD was not modified in any way. As the detector
      hardware and electronics remained the same, the change of the deuterium lamp for
      the Luxeon white LED allowed a direct comparison of their performances. Several
      anionic dyes as model analytes with absorption maxima between 450 and 600 nm were
      separated by CE in an electrolyte of 0.01 mol/L sodium tetraborate. The
      absorbance baseline noise as the key parameter was 5 * lower for the white LED
      lamp, showing clearly superior performance to the deuterium lamp in the
      available, i.e. visible part of the spectrum.

PMID- 21077242
TI  - Feasibility of SU-8-based capillary electrophoresis-electrospray ionization mass
      spectrometry microfluidic chips for the analysis of human cell lysates.
AB  - Monolithically integrated, polymer (SU-8) microchips comprising an
      electrophoretic separation unit, a sheath flow interface and an ESI emitter were
      developed to improve the speed and throughput of proteomics analyses. Validation
      of the microchip method was performed based on peptide mass fingerprinting and
      single peptide sequencing of selected protein standards. Rapid, yet reliable
      identification of four biologically important proteins (cytochrome C, beta
      lactoglobulin, ovalbumin and BSA) confirmed the applicability of the SU-8
      microchips to ambitious proteomic applications and allowed their use in the
      analysis of human muscle cell lysates. The characteristic tryptic peptides were
      easily separated with plate numbers approaching 10(6), and with peak widths at
      half height as low as 0.6 s. The on-chip sheath flow interface was also exploited
      to the introduction of an internal mass calibrant along with the sheath liquid
      which enabled accurate mass measurements by high-resolution Q-TOF MS.
      Additionally, peptide structural characterization and protein identification
      based on MS/MS fragmentation data of a single tryptic peptide was obtained using
      an ion trap instrument. Protein sequence coverages exceeding 50% were routinely
      obtained without any pretreatment of the proteolytic samples and a typical total
      analysis time from sampling to detection was well below ten minutes. In
      conclusion, monolithically integrated, dead-volume-free, SU-8 microchips proved
      to be a promising platform for fast and reliable analysis of complex proteomic
      samples. Good analytical performance of the microchips was shown by performing
      both peptide mass fingerprinting of complex cell lysates and protein
      identification based on single peptide sequencing.

PMID- 21077243
TI  - Electrophoretically deposited polyaniline nanotubes based film for cholesterol
      detection.
AB  - Polyaniline nanotube (PANI-NT) based films have been fabricated onto indium-tin
      oxide (ITO) coated glass plates via electrophoretic technique. These PANI-NT/ITO
      electrodes have been utilized for covalent immobilization of cholesterol oxidase
      (ChOx) using glutaraldehyde (Glu) as cross-linker. Structural, morphological and
      electrochemical characterization of PANI-NT/ITO electrode and ChOx/Glu/PANI
      NT/ITO bioelectrode have been done using FT-IR spectroscopy, SEM, electrochemical
      impedance spectroscopy and cyclic voltammetry techniques. Response studies of the
      ChOx/Glu/PANI-NT/ITO bioelectrode have been carried out using both linear sweep
      voltammetry and UV-Visible spectrophotometry. The results of the biosensing
      studies reveal that this bioelectrode can be used to detect cholesterol in wide
      detection range of 25-500 mg/dL with high sensitivity of 3.36 mA mg(-1) dL and
      fast response time of 30 s at pH 7.4. This bioelectrode exhibits very low value
      of Michaelis-Menten constant of 1.18 mM indicating enhanced interactions between
      cholesterol and ChOx immobilized onto this nanostructured PANI matrix.

PMID- 21077244
TI  - Determination of the potassium content of explosive residues using miniaturised
      isotachophoresis.
AB  - A new method has been developed to allow the determination of potassium in post
      explosion residues to be made using miniaturised isotachophoresis. The method is
      based on the use of a caesium leading ion with 4.5 mM 18-crown-6 ether added to
      retard the potassium to allow reliable determinations to be made. With the
      conditions selected no interference was noted from other small inorganic cations,
      such as ammonium, barium, calcium, magnesium, sodium or strontium. The method was
      successfully applied to the analysis of seven samples containing explosive
      residues obtained from the unconfined burning of several flash powders. The
      procedure was found to offer good linearity for potassium determinations over the
      concentration range of 1.25-150 MUg/mL with a coefficient of determination of
      0.999 achieved.

PMID- 21077245
TI  - Liposomes in chromatography.
AB  - The newest achievements in the application of liposomes in different
      chromatographic technologies such as high-performance liquid chromatography and
      electrically driven separation methods was compiled and critically evaluated. The
      employment of chromatographic methodologies for the determination of molecular
      parameters of biological importance is also discussed in detail. The future
      trends of the use of liposomes is also shortly discussed.

PMID- 21077246
TI  - Proteomic analysis of chondrocytes exposed to pressure.
AB  - Chondrocytes are the only cell type present in mature articular cartilage (2-5%
      of total tissue). The biological activities of the chondrocyte population are
      regulated by genetic, biologic and biochemical factors, as well as environmental
      factors (stress, flow and electric field). Although compressive forces within
      joint articular cartilage are required for maintenance of the normal composition
      of articular cartilage, there is a lack of knowledge about the number of pressure
      related proteins expressed in articular cartilage. Two-dimensional gel
      electrophoresis (2-DE) and high-performance liquid chromatography
      electrospray/tandem mass spectrometry (HPLC/ESI-MS/MS) were used to identify the
      levels of pressure-related proteins expressed by chondrocytes grown in the
      presence or absence of hydrostatic pressure. A total of 266 spots were excised
      from the gels and analyzed by HPLC/ESI-MS/MS. Functional classification of up
      regulated proteins indicated that energy and protein fate were the main
      biological processes occurring in pressurized chondrocytes. Furthermore, membrane
      bound transferrin-like protein p97, a marker of chondrocyte differentiation, was
      only expressed in chondrocytes under hydrostatic pressure. These data suggest
      that hydrostatic pressure can induce cell differentiation by increasing the
      expression level of energy metabolism- and protein fate-related proteins,
      indicating that hydrostatic pressure may be needed for normal biosynthesis and
      differentiation of articular chondrocytes.

PMID- 21077247
TI  - Profiling of Piper betle Linn. cultivars by direct analysis in real time mass
      spectrometric technique.
AB  - Piper betle Linn. is a traditional plant associated with the Asian and southeast
      Asian cultures. Its use is also recorded in folk medicines in these regions.
      Several of its medicinal properties have recently been proven. Phytochemical
      analysis showed the presence of mainly terpenes and phenols in betel leaves.
      These constituents vary in the different cultivars of Piper betle. In this paper
      we have attempted to profile eight locally available betel cultivars using the
      recently developed mass spectral ionization technique of direct analysis in real
      time (DART). Principal component analysis has also been employed to analyze the
      DART MS data of these betel cultivars. The results show that the cultivars of
      Piper betle could be differentiated using DART MS data.

PMID- 21077248
TI  - Simultaneous and group determination methods for designated substances by HPLC
      with multi-channel electrochemical detection and their application to real
      samples.
AB  - Many psychotropic substances are illegally available on the streets and/or via
      the Internet. This wide distribution has become a serious social problem. To
      control this problem, many substances have been controlled as 'designated
      substances' (Shitei-Yakubutsu) in Japan since April 2007 by the Pharmaceutical
      Affairs Law, including tryptamines, phenethylamines and piperazines. In the
      present study, simultaneous determination methods using HPLC with multi-channel
      electrochemical detection (MECD) were developed for the designated substances.
      The proposed methods utilizing online electrochemical oxidation are the first
      report on the simultaneous determination of various designated substances. The
      methods involve direct determination and require no complicated pretreatments
      such as fluorescence labeling. The designated substances were separated by
      reversed-phase chromatography using a TSK-gel ODS-100V (4.6 * 250 mm, i.d., 3 um)
      and gradient elution by a mixture of potassium phosphate buffer, methanol and
      acetonitrile. The total separation of 31 designated substances was successfully
      performed but required long chromatographic run times. Thus, the designated
      substances were divided into three groups: (1) tryptamines, (2) phenethylamines
      and (3) piperazines and others. They were then analyzed by HPLC-MECD as another
      separation method. The suitable applied voltages for each designated substance
      were determined based upon the hydrodynamic voltammogram. The limits of detection
      (signal-to-noise ratio of 3) of the designated substances for the most suitable
      voltages were in the range of 17.1 pg (5-MeO-MIPT) to 117 ng (indan-2-amine). The
      calibration curves based on the peak heights were linearly related to the amounts
      of the designated substances (R(2) > 0.999). Good accuracy and precision by intra
      day assay and inter-day assay were also obtained using the present procedures.
      The proposed methods were applied to the analyses of the designated substance in
      several real samples.

PMID- 21077249
TI  - Validation of an LC/MS method for the determination of gemfibrozil in human
      plasma and its application to a pharmacokinetic study.
AB  - Gemfibrozil, a fibric acid hypolipidemic agent, is increasingly being used in
      clinical drug-drug interaction studies as an inhibitor of drug metabolizing
      enzymes and drug transporters. The validation of a fast, accurate and precise
      LC/MS method is described for the quantitative determination of gemfibrozil in an
      EDTA-anticoagulated human plasma matrix. Briefly, gemfibrozil was extracted from
      human plasma by an acetonitrile protein precipitation method. The assay was
      reproducible with intra-assay precision between 1.6 and 10.7%, and inter-assay
      precision ranging from 4.4 to 7.8%. The assay also showed good accuracy, with
      intra-assay concentrations within 85.6-108.7% of the expected value, and inter
      assay concentrations within 89.4-104.0% of the expected value. The linear
      concentration range was between 0.5 and 50 ug/mL with a lower limit of
      quantitation of 0.5 ug/mL when 125 uL of plasma were extracted. This LC/MS method
      yielded a quick, simple and reliable protocol for determining gemfibrozil
      concentrations in plasma and is applicable to clinical pharmacokinetic studies.

PMID- 21077250
TI  - An LC-MS-MS method for quantitative determination of maraviroc (UK-427,857) in
      human plasma, urine and cerebrospinal fluid.
AB  - Maraviroc is a first-in-class CCR5 antagonist that shows potent anti-HIV-1
      activity in vitro and in vivo and is well tolerated in both healthy volunteers
      and HIV-1-infected patients. The method for determination of maraviroc (UK
      427,857) and its major metabolite (UK-408,027) in human plasma consists of a
      protein-precipitation procedure and analysis by liquid chromatography/tandem mass
      spectrometry using positive ion TurboIonSpray(r) ionization and multiple reaction
      monitoring. The assay has been validated over a concentration range of 0.500-500
      ng/mL for both analytes. The determinations of maraviroc in human cerebrospinal
      fluid (0.500-500 ng/mL) and in urine (5.00-5000 ng/mL) have also been validated
      but do not include measurement of the metabolite. The validations included
      extraction recovery, intra-assay and inter-assay precision and accuracy,
      stability of stock and spiking solutions, freeze-thaw stability, matrix
      stability, processed-extract stability, and evaluation of potential interferences
      from selected medications in plasma or urine.

PMID- 21077251
TI  - LC-MS/MS determination and pharmacokinetic study of albiflorin and paeoniflorin
      in rat plasma after oral administration of Radix Paeoniae Alba extract and Tang
      Min-Ling-Wan.
AB  - A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry
      method (LC-MS/MS) was developed and validated for simultaneous determination of
      albiflorin and paeoniflorin in rat plasma using geniposide as an internal
      standard. Plasma samples were extracted by solid-phase extraction.
      Chromatographic separation was carried out on a Zorbax SB-C(18) analytical column
      (150 * 2.1 mm * 5 um) with 0.1% formic acid-acetonitrile (70:30, v/v) as the
      mobile phase. Detection was performed by multiple reaction monitoring mode using
      electrospray ionization in the positive ion mode. The total run time was 3.0 min
      between injections. The calibration curves were linear over a range of 1-1000
      ng/mL for albiflorin and 2-2000 ng/mL for paeoniflorin. The overall precision and
      accuracy for all concentrations of quality controls and standards were better
      than 15%. Mean recovery was determined to be 87.7% for albiflorin and 88.8% for
      paeoniflorin. The validated method was successfully applied to the
      pharmacokinetic study of albiflorin and paeoniflorin in rat plasma after oral
      administration of Radix Paeoniae Alba extract and Tang-Min-Ling-Wan. The
      pharmacokinetic parameters showed that albiflorin and paeoniflorin from Tang-Min
      Ling-Wan were absorbed more rapidly with higher concentrations in plasma than
      that from Radix Paeoniae Alba extract. The results provided a meaningful basis
      for evaluating the clinical applications of traditional Chinese medicine.

PMID- 21077252
TI  - Enantioseparation of rabeprazole and omeprazole by nonaqueous capillary
      electrophoresis with an ephedrine-based ionic liquid as the chiral selector.
AB  - An ephedrine-based chiral ionic liquid, (+)-N,N-dimethylephedrinium
      bis(trifluoromethanesulfon)imidate ([DMP](+) [Tf(2) N](-) ), served as both
      chiral selector and background electrolyte in nonaqueous capillary
      electrophoresis. The enantioseparation of rabeprazole and omeprazole was achieved
      in acetonitrile-methanol (60:40 v/v) containing 60 mm[DMP](+) [Tf(2) N](-) . The
      influences of separation conditions, including the concentration of [DMP](+)
      [Tf(2) N](-) , the electrophoretic media and the buffer, on enantioseparation
      were evaluated. The mechanism of enantioseparation was investigated and
      discussed. Ion-pair interaction and hydrogen bonding may be responsible for the
      main separation mechanism.

PMID- 21077253
TI  - Development and validation of an LC-ESI-MS/MS method for simultaneous
      quantitation of olmesartan and pioglitazone in rat plasma and its pharmacokinetic
      application.
AB  - A simple, high-throughput and specific high-performance liquid chromatography
      tandem mass spectrometry method has been developed and validated according to the
      FDA guidelines for simultaneous quantification of olmesartan and pioglitazone in
      rat plasma. The bioanalytical method consists of liquid-liquid extraction and
      quantitation by triple quadrupole mass spectrometry using electrospray ionization
      technique, operating in multiple reaction monitoring and positive ion modes. The
      compounds were eluted isocratically on a C(18) column with a mobile phase
      consisting of a mixture of methanol and water (containing 0.5% formic acid) in a
      ratio of 9:1. The response to olmesartan and pioglitazone was linear over the
      range 0.01-10 ug/mL. The validation results demonstrated that the method had
      satisfactory precision and accuracy across the calibration range. Intra- and
      inter-day precisions ranged from 0.66 to 3.32 and from 0.94 to 2.93% (%CV),
      respectively. The accuracy determined at three quality control levels was within
      91.27-107.28%. There was no evidence of instability of the analytes in rat plasma
      following the stability studies. The method proved highly reproducible and
      sensitive and was successfully applied in a pharmacokinetic study after single
      dose oral administration of olmesartan and pioglitazone to the rat.

PMID- 21077254
TI  - Determination of aristolochic acid in urine using hollow fiber liquid-phase
      microextraction combined with high-performance liquid chromatography.
AB  - A simple and efficient hollow fiber liquid-phase microextraction (HF-LPME)
      technique in conjunction with high-performance liquid chromatography is presented
      for extraction and quantitative determination of aristolochic acid I in human
      urine samples. Several parameters influencing the efficiency of HF-LPME were
      investigated and optimized, including extraction solvent, stirring rate,
      extraction time, pH of donor phase and acceptor phase. Excellent sample clean-up
      was observed and good linearity with coefficient of 0.9999 was obtained in the
      range of 15.4-960 ug/L. This method provided a 230-fold enrichment factor and
      good repeatability with relative standard deviations (RSD) lower than 6.0%. The
      limit of detection value for the analyte in urine sample was 0.01 ug/L at a
      signal-to-noise ratio of 3. The extraction recovery from urine samples was 61.8%
      with an RSD of 9.71%.

PMID- 21077255
TI  - Development of a validated high-throughput LC-ESI-MS method for determination of
      sirolimus on dried blood spots.
AB  - A high-throughput liquid chromatography-electrospray ionization mass
      spectrometric (LC-ESI-MS) method for screening of sirolimus on dried blood spots
      (DBS) was developed and validated. It involves solvent extraction of a punch of
      DBS followed by reversed-phase LC on a relatively new monolithic column
      consisting of a silica rod with bimodal pore structure and detection by ESI-MS.
      The run time was less than 3 min with a very low backpressure at a flow rate of
      0.5 mL/min. The method can analyze more than 100 samples in an 8 h working day,
      including sample preparation. The assay was linear from 1 to 100 ng/mL. The mean
      recovery was 92.42%. The mean inter-day and intra-day precisions were 1.23 and
      1.41%, respectively. The developed method is simple, rapid and useful for
      clinical applications.

PMID- 21077256
TI  - Quantification of oxyresveratrol analog trans-2,4,3',5'-tetramethoxystilbene in
      rat plasma by a rapid HPLC method: application in a pre-clinical pharmacokinetic
      study.
AB  - A rapid HPLC method was developed and validated for the quantification of
      oxyresveratrol analog trans-2,4,3',5'-tetramethoxystilbene (oxyresveratrol
      tetramethyl ether, OTE) in rat plasma. Chromatographic separation was achieved on
      an RP-HPLC column, which was protected by a guard column through a 12 min
      gradient delivery of a mixture of acetonitrile-water at 50 degrees C. The UV
      absorbance at 325 nm was recorded. The retention time of OTE and trans-stilbene
      (internal standard) was about 7.7 and 8.4 min, respectively. The calibration
      curves were linear (R(2) >= 0.9986) with a lower limit of quantification of 15
      ng/mL. The intra- and inter-day variations, in terms of RSD, were all lower than
      9.8% while the intra-day and inter-day bias ranged from -8.3 to +9.2%. The
      pharmacokinetics of OTE was assessed in rats using 2-hydroxypropyl-beta
      cyclodextrin as a dosing vehicle. After intravenous administration, OTE possessed
      a long terminal elimination half-life (t(1/2) (lambdaz) = 481 +/- 137 min) and
      slow clearance (Cl = 29.1 +/- 3.7 mL/min/kg). Upon oral administration, OTE was
      rapidly absorbed. However, it only displayed minimal plasma exposure and its
      absolute oral bioavailability (F) was as low as 4.5 +/- 3.2%. Fortunately, the
      levels of OTE after single oral administration were sufficient to inhibit human
      cytochrome P450 1B1.

PMID- 21077257
TI  - DNA macroarray study of skin aging-related genes expression modulation by
      antioxidant plant extracts on a replicative senescence model of human dermal
      fibroblasts.
AB  - The formation of reactive oxygen species (ROS) is a widely accepted pivotal
      mechanism leading to skin aging. It increases with age, while the endogenous
      defense mechanisms that counter them decrease. This imbalance, called oxidative
      stress, leads to the progressive damage of cellular structures and results in
      accelerated aging. Antioxidant compounds can provide protection from endogenous
      and exogenous oxidative stress by scavenging free radicals. The main phenolic
      compounds of oak wood, mate leaf and benjoin resin antioxidant extracts were
      identified and the effects of these extracts on skin aging markers were evaluated
      using DNA macroarray technology. The transcriptional effect of the three
      antioxidant extracts was evaluated in vitro on a replicative senescence model of
      normal human dermal fibroblasts (NHDF), using a customized DNA macroarray
      specifically designed to investigate aging markers such as dermal structure, cell
      renewal, inflammatory response and oxidative stress mechanisms. Among the 149
      genes detected, the three antioxidant extracts presented a significant regulation
      of five genes involved in inflammatory response, cell renewal and antioxidant
      defenses. The collective transcriptional effects of these extracts suggest
      interesting antiaging properties which could be utilized in nutraceutical
      antiaging formulations.

PMID- 21077258
TI  - Antagonistic effects of Lycium barbarum polysaccharides on the impaired
      reproductive system of male rats induced by local subchronic exposure to 60Co
      gamma irradiation.
AB  - Lycium barbarum, a famous Chinese medicinal herb, has a long history of use in
      traditional medicine as an antioxidant and to promote sexual fertility.
      Polysaccharides are the most important functional constituents in L. barbarum
      fruits. In this study, male rats were exposed to subchronic (60)Co-gamma
      irradiation to investigate the effects of LBP on sperm quantity and motility,
      sexual ability, serum hormone levels, oxidative status and testicular tissue DNA
      damage on days 1, 7 and 14 of treatment. It was found that LBP significantly
      increased the sperm quantity and motility, shortened the erection, capture and
      ejaculation latencies, increased the number of captures and ejaculations, and
      improved the sexual ability of male rats. LBP also played a significant role in
      the recovery of serum testosterone levels, increased superoxide dismutase
      activity, decreased malondialdehyde levels, promoted oxidative balance and
      rescued testicular DNA damage. In conclusion, LBP has significant protective
      effects against damage induced by local subchronic exposure to (60)Co-gamma
      irradiation, allowing rats to achieve near-complete recovery with LBP treatment.

PMID- 21077259
TI  - Mode of action of peppermint oil and (-)-menthol with respect to 5-HT3 receptor
      subtypes: binding studies, cation uptake by receptor channels and contraction of
      isolated rat ileum.
AB  - Peppermint oil (Mentha * piperita L. (Lamiaceae) has been shown to exert potent
      antiemetic properties, but its mode of action has not yet been elucidated. Among
      its active constituents (-)-menthol is the most important. Three different in
      vitro models were used to investigate the effects on 5-HT(3) receptors (serotonin
      receptor subtype): [(14)C]guanidinium influx into N1E-115 cells which express 5
      HT(3) receptors, isotonic contractions of the isolated rat ileum and equilibrium
      competition binding studies using a radioactively labelled 5-HT(3) receptor
      antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3
      yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited
      [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as
      contractions of the ileum induced by serotonin. Neither the peppermint oil nor (
      )-menthol, however, was able to displace [(3)H]GR65630 from 5-HT(3) binding
      sites. It may be concluded that peppermint oil and (-)-menthol exert their
      antiemetic effect at least partly by acting on the 5-HT(3) receptor ion-channel
      complex, probably by binding to a modulatory site distinct from the serotonin
      binding site.

PMID- 21077260
TI  - Antidiabetic complications and anti-Alzheimer activities of sophoflavescenol, a
      prenylated flavonol from Sophora flavescens, and its structure-activity
      relationship.
AB  - It was previously reported that prenylated flavonols from Sophora flavescens are
      inhibitors of rat lens aldose reductase (RLAR), human recombinant aldose
      reductase (HRAR), advanced glycation endproducts (AGE), beta-secretase (BACE1)
      and cholinesterases (ChE). Based upon structure-activity relationships, 3,4'
      dihydroxy flavonols with a prenyl or lavandulyl group substitution at the C-8
      position, and a hydroxy group at the C-5, are important for such inhibition. In
      our ongoing study to isolate active principles from S. flavescens by an activity
      guided isolation procedure, further detailed phytochemical investigations of the
      CH(2)Cl(2) fraction were conducted via repeated chromatography over silica gel
      and Sephadex LH-20 columns. This ultimately resulted in the isolation of a
      promising active sophoflavescenol with higher inhibitory activities among the
      current prenylated flavonols isolated from S. flavescens against RLAR, HRAR, AGE,
      BACE1 and ChEs. The results further support that 3,4'-dihydroxy flavonols with a
      prenyl or lavandulyl substitution at the C-8 position and a methoxy group at C-5
      represent a new class of RLAR, HRAR and AGE inhibitors. Nevertheless, the C-5
      hydroxyl group of prenylated flavonoids is important for inhibition of BACE1 and
      ChEs, indicating that the hydroxyl group at C-5 might be the main contributor to
      the augmentation and/or modification of prenylated flavonol activity.

PMID- 21077261
TI  - Stimulation of osteoblastic differentiation and mineralization in MC3T3-E1 cells
      by yeast hydrolysate.
AB  - In a previous study, it was reported that yeast hydrolysate (YH) was effective in
      promoting bone growth in Sprague-Dawley (SD) rats. To further clarify the
      mechanism of YH, the effects of YH on proliferation, differentiation and gene
      expression in vitro were investigated using osteoblastic cell lines (MC3T3-E1).
      Cell proliferation increased significantly as much as 110% of the basal value
      when cells were treated with 100 ug/mL of YH. Alkaline phosphatase (ALP) activity
      increased significantly with a YH concentration of 25-100 ug/mL, and the activity
      increased 152% that of the control at 100 ug/mL. The calcium content increased as
      much as 129% at 100 ug/mL YH. The gene expression levels of ALP and collagen type
      II (COL II) significantly increased approximately 1.3-fold and 1.7-fold of
      control, respectively, at 100 ug/mL. YH increased significantly the mRNA level of
      bone sialoprotein (BSP) but not in a dose-dependent manner. The mRNA levels of
      bone morphogenetic proteins (BMP)-2, BMP-4, collagen type I (COL I) and
      osteonectin (ON) did not increase. In summary, YH increased the proliferation of
      osteoblasts and directly stimulated ALP and bone matrix proteins (e.g. BSP, COL
      II), and these increases trigger osteoblastic differentiation (e.g. mineralized
      nodule formation).

PMID- 21077262
TI  - Effect of mollugin on apoptosis and adipogenesis of 3T3-L1 preadipocytes.
AB  - The effect of mollugin, isolated from the roots of Rubia cordifolia L., on cell
      viability, apoptosis and adipogenesis in 3T3-L1 preadipocytes was investigated.
      The inhibitory effect of mollugin (40-60 uM) on cell viability was more
      significant in differentiated adipocytes than in 3T3-L1 preadipocytes. In 3T3-L1
      cells, the cytotoxicity of mollugin was accompanied by apoptotic events including
      mitochondrial membrane potential (Deltapsim) loss and activation of caspase-9, -3
      and -7, leading to PARP degradation. Although the presence of 20 uM mollugin
      during induced adipocytic differentiation of 3T3-L1 cells for 6 days failed to
      affect the cell viability, it could almost completely abrogate the
      differentiation-associated morphology change and intracellular lipid
      accumulation. A similar level of inhibition was observed, when 20 uM mollugin was
      present during the early stage (D0-D2) of the differentiation period. In
      addition, the expression of C/EBPalpha, PPARgamma1 and PPARgamma2 was
      significantly down-regulated. The presence of 20 uM mollugin during either middle
      stage (D2-D4) or late stage (D4-D6) of the differentiation period, however,
      caused the inhibition to a lesser extent. These results indicated that mollugin
      at high concentrations (40-60 uM) exerted cytotoxicity via inducing apoptosis,
      whereas mollugin at a low concentration (20 uM) suppressed adipocytic
      differentiation without exerting cytotoxicity in 3T3-L1 preadipocytes.

PMID- 21077263
TI  - Oligomerized grape seed proanthocyanidins ameliorates isoproterenol-induced
      cardiac remodeling in rats: role of oxidative stress.
AB  - The effects of oligomerized grape seed proanthocyanidins (GSP) on haemodynamics,
      cardiac hypertrophy and fibrosis as well as apoptosis signal-regulating kinase 1
      (ASK1) and nuclear factor-kappaB (NF-kappaB) cascades in isoproterenol (Iso)
      induced cardiac remodelling (CR) rat model were investigated, in addition, the
      serum SOD activities and MDA content were assayed. Rats were treated with Iso to
      induce CR and were given distilled water or GSP for 1 week. Control rats received
      vehicle instead of Iso. Administration of GSP markedly alleviated the elevation
      of the left ventricle weight (LVW)/body weight (BW), heart weight (HW)/body
      weight (BW) ratio and cross-sectional area of cardiomyocytes, decreased collagen
      deposition in the heart, and improved the haemodynamic index. Meanwhile,
      treatment with GSP significantly ameliorated oxidative stress by improving SOD
      activities and decreasing MDA formation. Moreover, GSP apparently inhibited the
      expression ASK1, NF-kappaB and its targeted gene - COX-2. These findings suggest
      that administration of GSP has the potential to attenuate Iso-induced CR by
      repressing oxidative stress and inhibiting the activation of the cellular
      signaling cascades involving the ASK1 and NF-kappaB pathways, at least in part,
      providing a molecular mechanism for the cardioprotective effect of GSP.

PMID- 21077264
TI  - Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the
      elevated plus maze in mice.
AB  - The purpose of this study was to characterize the putative anxiolytic-like
      activity of fractions prepared from a hydroethanol extract of Passiflora
      incarnata L. using the elevated plus-maze (EPM) in mice. The fractions were
      prepared as published recently, yielding a butanol, petroleum ether and
      chloroform fraction. From the tested fractions, the butanol fraction showed
      significant increases in the number of open arm entries in the EPM in
      concentrations of 2.1 mg/kg and 4.2 mg/kg corresponding to 150 and 300 mg/kg of
      the original extract. The highest activity was found for the chloroform fraction
      in doses of 0.17 mg/kg (10.0 +/- 1.9, p < 0.001) and 0.34 mg/kg (6.6 +/- 0.86; p
      < 0.05) which corresponds to a total extract dose of 150 and 300 mg/kg,
      respectively. Interestingly, the petroleum ether fraction did not show any
      effects in the elevated plus maze. A sedative or stimulatory effect of each of
      the fractions could be excluded, since none of the compounds had an influence on
      the total distance that the animals covered during the observation period. The
      results suggest that the active principle of passion flower seems to be in the
      chloroform fraction and to a lower extent in the butanol fraction.

PMID- 21077265
TI  - Protective effect of flaxseed oil on renal injury in hyperlipidaemic rats: the
      effect of flaxseed oil on hyperlipidaemia.
AB  - This study evaluated the possible effects of flaxseed oil on renal damage
      associated with hyperlipidaemic rats. Wistar albino male rats were divided into
      three groups. Group I was fed with a pellet chow. Group II was fed with a high
      cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added
      to the pellet chow. Group III was fed with the same HCD, but were orally treated
      with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started
      1 week before and continued throughout the 22 weeks of the HCD. At the end of the
      experiment, renal tissue and blood samples were collected. The biochemical and
      histopathological findings confirmed renal damage in hypercholesterolaemia
      conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in
      the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed
      that lowered serum lipid was accompanied by a decreased deposition of neutral
      lipid. Flaxseed oil effectively reversed these abnormalities, verifying the
      protective effects of flaxseed oil in ameliorating renal injuries associated with
      hypercholesterolaemia.

PMID- 21077266
TI  - The clinical value of a cluster of patient history and observational findings as
      a diagnostic support tool for lumbar spine stenosis.
AB  - OBJECTIVE: The study aims to create a diagnostic support tool to indicate the
      likelihood of the presence of lumbar spinal stenosis (LSS) using a cluster of
      elements from the patient history and observational findings. DESIGN: The study
      is case based and case controlled. SETTING: The study was performed in the
      tertiary care of a medical center. SUBJECTS: There were a total of 1,448 patients
      who presented with a primary complaint of back pain with or without leg pain.
      METHODS: All patients underwent a standardized clinical examination. The
      diagnosis of LSS was made by one of two experienced orthopaedic surgeons based on
      clinical findings and imaging. Data from the patient history and observational
      findings were then statistically analysed using bivariate analysis and
      contingency tables. RESULTS: The most diagnostic combination included a cluster
      of: 1) bilateral symptoms; 2) leg pain more than back pain; 3) pain during
      walking/standing; 4) pain relief upon sitting; and 5) age>48 years. Failure to
      meet the condition of any one of five positive examination findings demonstrated
      a high sensitivity of 0.96 (95% CI=0.94-0.97) and a low negative likelihood ratio
      (LR-) of 0.19 (95% CI=0.12-0.29). Meeting the condition of four of five
      examination findings yielded a LR+ of 4.6 (95% CI=2.4-8.9) and a post-test
      probability of 76%. CONCLUSION: The high sensitivity of the diagnostic support
      tool provides the potential to reduce the incidence of unnecessary imaging when
      the diagnosis of LSS is statistically unlikely. In patients where the condition
      of four of the five findings was present, the post-test probability of 76%
      suggests that imaging and further workup are indicated. This is an inexpensive
      but powerful tool, with a potential to increase diagnostic efficiency and reduce
      cost by narrowing the indications for imaging.

PMID- 21077268
TI  - Simultaneous multiresidue determination of 48 pesticides in Yeongsan and Sumjin
      River water using GC-NPD and confirmation via GC-MS.
AB  - In a continuation of our earlier work, a multiresidual analytical method using 48
      frequently used neutral pesticides in a water matrix was developed and validated
      in this study. The samples were extracted with dichloromethane and the pesticides
      were analyzed via GC-NPD followed by confirmation with GC-MS. Good linearity was
      detected over a concentration range of 0.01-1.0 microg/mL with correlation
      coefficients (r(2) ) in excess of 0.982. The recoveries were measured between
      70.7 and 111.4% for the majority of the targeted pesticides with relative
      standard deviations (RSDs) of less than 20%. The LODs and LOQs were in ranges of
      0.1-2 and 0.33-6.6 microg/L, respectively. A total of 66 water samples were
      collected from different locations in Yeongsan and the Sumjin River, Republic of
      Korea, and were analyzed in accordance with the developed method. None of the
      water samples were determined to contain any of the targeted pesticides. The
      method has been shown to be simpler, faster, and more cost-effective than the
      method established by the Environmental Protection Agency (EPA).

PMID- 21077269
TI  - Definition of postthrombotic disease.

PMID- 21077270
TI  - Natural history of postthrombotic disease: Transition from acute to chronic
      disease.

PMID- 21077271
TI  - Critical issues in deep vein thrombosis prevention.

PMID- 21077272
TI  - The effectiveness of deep vein thrombosis prevention.

PMID- 21077273
TI  - Critical issues in ulcer prevention in postthrombotic disease.

PMID- 21077274
TI  - Evidence of prevention and treatment of postthrombotic syndrome.

PMID- 21077275
TI  - Critical issues in preventing post-thrombotic re-ulceration.

PMID- 21077276
TI  - Anti-neutrophil cytoplasmic antibodies target sequential functional proteinase 3
      epitopes in the sera of patients with Wegener's granulomatosis.
AB  - Many patients with Wegener's granulomatosis (WG) have anti-neutrophil cytoplasmic
      antibodies (c-ANCA). Aside from being a diagnostic marker, these autoantibodies
      may play roles in disease pathogenesis. Proteinase 3 (PR3) is the primary target
      of c-ANCA in WG patient sera. Of 60 c-ANCA-positive patients, 10 patients were
      selected for detailed humoral epitope analysis, contingent upon serum
      availability, using samples with positive levels of anti-PR3 by enzyme-linked
      immunosorbent assay (ELISA). Sequential epitope specificities of anti-PR3
      antibodies detected by screening the maximally overlapping solid-phase
      octapeptides of PR3 showed seven major common antigenic targets bound by WG
      patient sera. These include novel and previously identified sequential PR3
      epitopes bound by c-ANCA. B cell epitope prediction algorithms identified all or
      part of the seven defined epitopes. Several epitopes share sequence and
      structural proximity with functional sites, including the catalytic triad and
      proposed binding sites of other potential proteins [PR3 complementary peptide and
      soluble endothelial protein C receptor (sEPCR)]. Epitope 4 (VVLGAHNVRTQ) had the
      highest binding prevalence (90%) and epitope 2 (AQPHSRPYMAS) has the highest
      average reactivity of the antigenic regions. Epitope 4 includes the interaction
      site between sEPCR and PR3 which may serve as an important interaction to down
      regulate inflammation. Epitopes 3, 5 and 7 are in direct proximity to amino acids
      that form the catalytic triad of the protein. c-ANCA targets both unique and
      previously known sequential PR3 peptides. This information may prove useful in
      understanding anti-PR3-mediated disease pathogenesis in systemic vasculitides.

PMID- 21077277
TI  - Increased expression of chemokine receptor CCR3 and its ligands in ulcerative
      colitis: the role of colonic epithelial cells in in vitro studies.
AB  - Human colonic epithelial cells express T helper type 1 (Th1)-associated
      chemoattractants, yet little is known about the production of Th2-associated
      chemoattractants. CCL11/eotaxin-1, CCL24/eotaxin-2 and CCL26/eotaxin-3 are known
      to attract CCR3-expressing, Th2-polarized lymphocytes. We studied constitutive
      and inflammation-induced expression and production of CCR3 together with its
      ligands in the colon and peripheral blood of patients with inflammatory bowel
      disease (IBD) by flow cytometry, reverse transcription-polymerase chain reaction
      (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). We further defined the
      regulated expression of these chemokines by RT-PCR and ELISA using cultured human
      epithelial cell lines. A higher fraction of peripheral T lymphocytes were found
      to be positive for CCR3 in patients with ulcerative colitis (UC) compared to
      Crohn's disease (CD), while almost no CCR3(+) T cells were found in normal
      controls (NC). Similarly, higher and more frequent expression of CCR3 was
      observed in colonic biopsies from patients with UC, regardless of the disease
      activity, when compared to CD or NCs. Serum CCL11/eotaxin-1 was increased
      significantly in UC (306 +/- 87 pg/ml) and less so in CD (257 +/- 43 pg/ml),
      whereas CCL24/eotaxin-2, and CCL26/eotaxin-3 were increased only in UC. Colonic
      expression of the three chemokines was minimal in NCs but high in inflammatory
      bowel diseases (especially UC) and was independent of disease activity. Th2, and
      to a lesser extent Th1, cytokines were able to induce expression and production
      of all three eotaxins from colonic epithelial cells in culture. CCR3 and ligands
      over-expression would appear to be a characteristic of UC. The production of CCR3
      ligands by human colonic epithelial cells suggests further that epithelium can
      play a role in modulating pathological T cell-mediated mucosal inflammation.

PMID- 21077279
TI  - IEEE Visualization Conference and IEEE Information Visualization Conference
      proceedings 2010. Preface.

PMID- 21077280
TI  - Inhibition of corneal neovascularization after alkali burn: comparison of
      different doses of bevacizumab in monotherapy or associated with dexamethasone.
AB  - BACKGROUND: To compare the effects of different doses of bevacizumab with both
      saline and dexamethasone on inflammatory angiogenesis in the rat cornea induced
      by small chemical lesions. METHODS: Corneal chemical cauterization was performed
      on 24 rats. Animals were divided randomly into six groups and received a daily
      subconjunctival injection for 7 days of: balanced salt solution 0.1 mL or
      dexamethasone phosphate 4 mg/day or bevacizumab 2.5 mg/day, 3.75 mg/day, 5.0
      mg/day or bevacizumab 5.0 mg/day + dexamethasone phosphate 4 mg/day. Clinical
      examination under slitlamp was performed daily for 7 days to evaluate corneal
      opacity and vessel size evolution. Computer assisted quantitative image analysis
      was used to measure the total corneal area covered by neovascularization.
      RESULTS: At final examination, the dexamethasone, bevacizumab 5.0 mg/day and
      dexamethasone + bevacizumab groups showed a significant lowering in corneal
      opacity score as compared with control (P = 0.024, P = 0.006 and P = 0.013,
      respectively). Also, a significant reduction on new vessels size score was
      observed. Surface of corneal neovascularization was significantly reduced in
      dexamethasone, bevacizumab 5.0 mg/day and dexamethasone + bevacizumab groups
      compared with control (P =0.045, P = 0.047 and P = 0.044, respectively).
      CONCLUSION: Our study demonstrates the ability of a 5.0 mg/day bevacizumab
      subconjunctival injection, in monotherapy or associated with dexamethasone, to
      cause a short-term involution of corneal neovascularization after corneal alkali
      burn. Combination of both of these treatments may have advantages to monotherapy
      approaches.

PMID- 21077278
TI  - Down-regulation of single immunoglobulin interleukin-1R-related molecule
      (SIGIRR)/TIR8 expression in intestinal epithelial cells during inflammation.
AB  - Single immunoglobulin (Ig) interleukin-1R-related molecule (SIGIRR) is an Ig-like
      membrane protein critical for negative regulation of Toll-like receptor (TLR)-4
      mediated signalling. We investigated SIGIRR expression and its regulation
      mechanism in intestinal epithelial cells (IECs) during inflammation. Endoscopic
      biopsy specimens were obtained from active and inactive colonic mucosa of
      ulcerative colitis (UC) patients, then SIGIRR expression was examined using real
      time polymerase chain reaction (PCR) and immunohistochemistry (IH). Mice
      experimental colitis models were established by administrations of sulphonic acid
      (TNBS) and dextran sodium sulphate (DSS), and epithelial expression of SIGIRR was
      examined using real-time PCR, IH and flow cytometry. The effects of
      lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-alpha on SIGIRR
      expression were evaluated in vitro using cultured IECs. To elucidate SIGIRR
      expression regulation in IECs, binding ability of the transcription factor SP1 at
      the responsive element of the SIGIRR promoter was examined using gel-shift and
      chromatin immunoprecipitation (ChIP) assays. In human colonic samples, SIGIRR was
      expressed mainly in IECs at levels significantly higher in inactive compared to
      active mucosa. In the mice, SIGIRR colonic expression decreased rapidly after
      colitis development and returned gradually to basal levels. Experimental colitis
      mediated down-regulation of SIGIRR in IECs was also confirmed by IH and flow
      cytometry results. Further, inflammatory conditions induced by TLR ligands and
      TNF-alpha caused significant down-regulation of SIGIRR expression in IECs, which
      was dependent upon decreased SP1 binding at the responsive element of the SIGIRR
      promoter. We found that SIGIRR is expressed in IECs and serves as a negative
      regulator to maintain gut innate immunity, which is down-regulated during
      inflammation by inhibition of an SP1-mediated pathway.

PMID- 21077281
TI  - New test for long QT syndrome.

PMID- 21077282
TI  - [Application of digital technology on imaging and minimally invasive anatomy in
      gastrointestinal surgery].

PMID- 21077283
TI  - Proceedings and abstracts of the 2009 Heart-Brain Summit.

PMID- 21077284
TI  - Retraction notice to "Peroxisome proliferator-activated receptor alpha controls
      hepatic heme biosynthesis through ALAS1" J. Mol. Biol. 388/2 (2010) 225-238.

PMID- 21077285
TI  - [A simple disk diffusion test to identify beta-lactamase-negative, ampicillin
      resistant Haemophilus influenzae--application of cephalexin, cefsulodin and
      cefaclor disks].
AB  - Currently, beta-lactamase-negative (BLN) ampicillin-resistant (AR) strains of
      Haemophilus influenzae are prevalent in Japan. BLNAR strains are defined by the
      presence of specific mutation(s) in the ftsI gene but are not phenotypically
      distinguishable by ampicillin (ABPC) susceptibility. In the present study, we
      showed that cephalexin (CEX), cefsulodin (CFS), and cefaclor (CCL) disk diffusion
      tests can be effectively used to identify BLNAR strains. A total of 169 clinical
      isolates of BLN H. influenzae, consisting of 113 of BLNAR and 56 of BLN,
      ampicillin-susceptible (AS), were included. All the isolates were genetically
      defined by detection of the TEM gene and partial sequencing of the ftsI gene. The
      Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution
      and disk diffusion tests for ABPC provided 20% and 19% false susceptible rates,
      respectively. Alternatively, 34 cephem agents were tested using disk diffusion.
      Of the agents tested, CEX, CFS, and CCL disks could effectively discriminate
      between BLNAR and BLNAS isolates. All the BLNAS isolates showed visible growth
      inhibitory zones around CEX and CFS disks, but 108 (95.6%) and 106 (93.8%) BLNAR
      isolates did not. The results indicated 100% predictive values (PVs) for BLNAR
      and PVs for BLNAS were 91.8% for CEX and 88.9% for CFS. The CLSI-based
      interpretations for CCL (> or =20 mm) also highly correlated with BLNAR and
      BLNAS, PVs for BLNAR and for BLNAS being 100% and 93.3%, respectively. With
      simplicity and discriminability of the test method, we recommend a CEX disk
      diffusion test in combination with a rapid beta-lactamase test to identify BLNAR
      isolates in clinical laboratories.

PMID- 21077286
TI  - [Establishing indicators for diagnosis of cholinergic crisis].
AB  - Cholinergic crisis is an adverse effect of an anticholinesterase agent, which is
      one of the cholinergic agents. Cholinergic crisis may induce serious conditions
      such as breathing difficulties. Cholinergic crisis is often diagnosed by an
      abnormally low level of serum cholinesterase (ChE). However, ChE value is not an
      appropriate indicator of cholinergic crisis since it has a high inter-individual
      variation, even though its intra-individual variation is low. Therefore, an
      indicator with less inter-individual variation capable of preventing the risk of
      cholinergic crisis was investigated. The results of correlation test between ChE
      and serum albumin (Alb) showed a strong positive correlation; r = 0.778 in BCG
      method(Bromo cresol green method) and r = 0.766 in the BCP-improved method for
      Alb. In addition, the variations of Alb values are much lower than the drastic
      depression of ChE values in cholinergic crisis. Thus, it is considered that the
      ratio of ChE and Alb (ChE/Alb) can be a useful indicator of cholinergic crisis.
      As a result of ROC (Receiver operating characteristic) analysis, the ratios of
      ChE and Alb values using the BCG method (ChE/Alb (BCG)) were 20.7, 87.0, 156.8
      for the Cutoff value, Likelihood ratio and Odds ratio respectively. When using
      the BCP-improved method for Alb, the ratios of ChE and Alb (ChE/Alb(BCP
      improved)) were 25.0, 93.7, 180.1 for the Cutoff value, Likelihood ratio and Odds
      ratio respectively. The ChE/Alb ratio appears to be an excellent indicator of
      cholinergic crisis diagnosis since it shows a high likelihood ratio as well as a
      high odds ratio.

PMID- 21077287
TI  - [Quantitative estimation of preanalytical variables which may influence the
      determinations of prothrombin time (PT) and activated partial thromboplastin time
      (APTT)].
AB  - Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests
      principally measure the time for a fibrin clot developed in citrated plasma after
      activation. For the complexity of chemical reactions, a number of preanalytical
      variables potentially influence the outcome of results. In the present study, we
      evaluated some preanalytical variables frequently encountered in clinical
      settings. The volumes of citrated whole-blood specimens collected from inpatients
      widely varied from 0.99 ml to 2.90 ml indicating 1.6% of unacceptable rate,
      whereas none of the specimens from outpatients was out of acceptable range. The
      citrated whole-blood volume significantly affected the determinations of both PT
      and APTT; the results indicating the more volume the longer clotting time. Also,
      whole-blood specimens collected in EDTA2K revealed significantly prolonged PT and
      APTT values in healthy subjects and the patients with anticoagulant therapy of
      heparin and of warfarin. Storage conditions, time and temperature might influence
      the PT and APTT values. In particular, citrated whole-blood specimens stood at
      room temperature revealed the prolonged clotting time in APTT assay by hours. The
      effects of other variables evaluated such as a half-volume adjustment, needle
      gauge or syringe type were negligible. With these results, it was concluded that;
      first, an accurate venipuncture is critical, particularly venipuncture from
      patients in wards where many different physicians and nurses are in charge and in
      changing by days. Secondly, the citrated whole-blood specimens should be assayed
      quickly without any unnecessary storage at room temperature beyond four hours.

PMID- 21077288
TI  - [Electrophysiological tests in a case of Hashimoto's encephalopathy].
AB  - Hashimoto's encephalopathy is regarded as an autoimmune disorder that appears in
      patients with anti thyroid antibodies. The thyroid function tests of the patients
      are not necessarily abnormal, which sometimes makes the diagnosis difficult.
      Since most of the patients show consciousness disturbance, psychiatric symptoms,
      and cognitive function decline, Hashimoto's encephalopathy must be distinguished
      from other disorders showing dementia. We performed the electrophysiological
      tests on a 38 year old woman with Hashimoto's encephalopathy. Event-related
      potentials showed impaired cognitive function, and somatosensory evoked
      potentials and motor evoked potentials showed abnormalities of central nervous
      system. Although the steroid pulse therapy with the following oral prednisolone
      treatment resulted in the remission of symptoms, results of electrophysiological
      tests remained unimproved. Thus the disease course of the patient should
      carefully be monitored, and the clinical importance of these tests in Hashimoto's
      encephalopathy may be further considered.

PMID- 21077289
TI  - [Data transformation and normalization].
AB  - When we analyze measured values by statistical techniques, we usually use a
      parametric method. It is necessary for measured values to show a normal
      distribution. Therefore, we must confirm that the distribution is normal, whereby
      a histogram shows that the distribution of data points is symmetrical above and
      below the mean. When measured values do not show a normal distribution, power
      transformation (square root transformation, logarithmic transformation) must be
      performed. We can evaluate the presence of normality by three methods: viewing a
      histogram, through skewness and kurtosis values, and Kolmogorov-Smirnov method's
      p-value. Because Kolmogorov-Smirnov's method is influenced by outliers, attention
      is necessary regarding the interpretation of p-values. For example, if we
      calculate reference intervals from clinical testing data, we calculate a
      parameter(mean and standard deviation) and set X +/- 2SD to upper and lower
      limits, respectively. When we evaluate the reference intervals, a range including
      95% of the central part of sample is important. Identification of the
      distribution type based on the diagonal linear pattern of normal quantile plots
      may be the most reliable in my experience.

PMID- 21077290
TI  - [The values of multi-laboratories serum values evaluation].
AB  - The members of 23 laboratories, ten clinical laboratory centers and thirteen
      hospital laboratories in the Kinki District participated in share their clinical
      laboratory data. In this joint work, we cross-checked twenty-seven serum values,
      and all data from the 23 laboratories well accorded; however, several values,
      such as urea nitrogen, calcium, and albumin needed to be standardized to share
      the laboratory data.

PMID- 21077291
TI  - [Contribution and application of glycoscience to clinical chemistry].
AB  - Glycoconjugates play pivotal and crucial roles in various biological processes,
      and it is thus believed that abnormal structural changes in the sugar chains of
      glycoconjugates are closely associated with the pathophysiology and clinical
      implications of many diseases. Many studies have identified and characterized the
      genes for glycosyltransferases and other related enzymes that are involved in the
      biosynthesis of sugar chains. Functional analyses of sugar chains using
      genetically engineered cells and organisms have clarified the biochemical bases
      for both the assembly and disease-related structural alteration of sugar chains.
      The findings obtained to date have been successfully applied to improve the
      diagnostic value of oligosaccharide biomarkers for diseases and also contributed
      to the establishment and/or development of therapeutic glycoproteins such as
      antibody-based drugs and some biofactors. In this article, the contribution and
      application of glycoscience to medicine, particularly clinical chemistry, will be
      described.

PMID- 21077292
TI  - [Chronic liver disease related to impaired glucose tolerance].
AB  - Obesity has become a pandemic disease causing a variety of lifestyle-related
      diseases, such as hypertension, dyslipidemia, diabetes mellitus, liver cirrhosis
      and hepatocellular carcinoma; therefore obesity has become an important health
      issue all over the world. Obesity was suggested to cause a chronic liver disease
      called nonalcoholic steatohepatitis (NASH) and to promote the progression of NASH
      to liver cirrhosis and hepatocellular carcinoma 30 years ago and this was proven
      20 years ago. Today, 1% of the Japanese population is suffering from NASH. Twenty
      percent of NASH patients, 0.2 million patients, are suggested to develop liver
      cirrhosis latently in the next decade, and are at a serious risk of developing
      hepatocellular carcinoma. Indeed, diabetes mellitus has become prevalent among
      the Japanese population and 10% die from chronic liver disease, but few doctors
      are able to recognize liver cirrhosis and hepatocellular carcinoma in patients
      with diabetes mellitus. It is a serious health issue to ignore such risk factors
      that threaten life in Japan. There are many chronic liver diseases with fatty
      liver, and nonalcoholic fatty liver disease (NAFLD), a chronic liver disease of
      unknown etiology, affects 14% of the Japanese population today. As NASH is the
      most progressive form of this disease, it has become a very important health
      issue to let doctors know how to recognize patients with NAFLD. In this paper, we
      discuss how to recognize NAFLD, including NASH, in our outpatient clinic.

PMID- 21077293
TI  - [Oral candidiasis: clinical features and control].
AB  - Candidiasis is the most commonly encountered fungal infection, and oral
      candidiasis is often observed as a local opportunistic infection. Oral
      candidiasis is clinically divided into three types: acute forms, chronic forms,
      and Candida-associated lesions. Candida adhesion and multiplication are largely
      regulated by the local and systemic factors of the host. The local factors
      include impairment of the oral mucosal integrity, which is usually impaired by
      hyposalivation, anticancer drugs/radiation for head and neck cancers, denture
      wearing, a decrease in the oral bacterial population, and poor oral hygiene.
      Among Candida species, oral candidiasis is mostly caused by Candida albicans (C.
      albicans), C. glabrata, or C. tropicalis. Oral Candida induces a variety of
      symptoms, such as oral mucosal inflammation manifesting as an uncomfortable
      feeling, pain, erythema, erosion, taste abnormalities, and hyperplasia of the
      oral mucosa. Candida overgrowth in the oral cavity may disseminate to distant
      organs. Therefore, in order to avoid the sequelae of systemic candidiasis, oral
      candidiasis should be rapidly controlled. Oral candidiasis is usually treated by
      the local application of antifungal drugs. However, oral candidiasis occasionally
      escapes the control of such local treatment due to the development of multi-drug
      resistant Candida strains and species or due to the suppression of salivation or
      cellular immune activity. When drug-resistant strains are suspected as the
      pathogens and when the host is generally compromised, the oral administration of
      combinations of antifungal drugs, enhancement of cellular immune activity, and
      improvement of the nutritional condition are recommended.

PMID- 21077294
TI  - [Clinical features of obsessive-compulsive disorder with pervasive developmental
      disorder].
AB  - Recently, psychiatrists have been paying attention to the presence of PDD
      (Pervasive Developmental Disorder) in difficult cases of mental disorder. We have
      found that patients with treatment-resistant OCD (Obsessive-Compulsive Disorder)
      are very likely to have PDD. If the presence of PDD can be recognized at an early
      stage based on the clinical features of patients with OCD, it would lead to
      effective treatment. However, there has been little research on the epidemiology
      of OCD patients with PDD, especially in adults. In this study, we investigated
      the percentage of PDD in adult OCD and the clinical characteristics of OC
      symptoms, comparing between OCD patients with or without diagnoses of PDD. The
      results showed that, in 48 patients with OCD, as many as 13 (27%) were diagnosed
      with PDD (PDD+). We identified several items in the Y-BOCS (Yale-Brown Obsessive
      Compulsive Disorder) symptom checklist that showed significantly higher rates in
      PDD+. In the 'Obsession' checklist, the items were obsession with need for
      symmetry or exactness, needing to know or remember and bothered by certain
      sounds/noises and the fear of losing things. In the 'Compulsion' checklist, the
      items were checking, repetition, ordering/ arranging, and hoarding/collecting
      compulsions. Among these items, needing to know or remember, hoarding/collecting
      compulsion, and the fear of losing things seemed to be closely related. The need
      to know or remember was considered to be the core factor. This relationship was
      found only in PDD+, and so it may prove useful in clinical guides to identify
      PDD+ among patients with OCD.

PMID- 21077295
TI  - [Intervention for psychotic experience involved in offending behavior].
AB  - Cognitive behaviour therapy for psychosis (CBTp) as an adjunct to standard
      psychiatric care can make substantial difference in symptom distress, insight,
      and adherence to treatment. However, studies on the effect of cognitive behaviour
      therapy on offending behaviours influenced by psychotic experience are in its
      very early stage. This paper summarizes the conceptualization, treatment
      programme development, and individual therapy to address psychotic experience
      involved in offending behaviours in mentally disordered offenders (MDOs). It is
      argued that, 1) intensive intervention is recommended for those MDOs with general
      risk factors in addition to psychosis-related-risk factors, 2) MDOs may benefit
      from CBTp and general offending behaviour programmes, 3) it is important to focus
      on aggression-neutralization cognitions.

PMID- 21077296
TI  - [Treating drug dependent patients through outpatient group therapy-Serigaya
      Methamphetamine Relapse Prevention Program (SMARPP)].
AB  - Drug addiction in Japan is a field of clinical psychiatry that occasionally poses
      questions concerning legal status of the patients abusing illicit drugs. In other
      countries, continuing care perspective and harm reduction policy is gradually
      becoming the main current of the addiction psychiatry. There are several clinical
      projects in Japanese psychiatric hospitals and public health centers attempting
      to motivate and treat drug dependent patients through outpatient group therapy.
      SMARPP is one of such projects with promising results concerning the efficacy on
      treatment retention.

PMID- 21077297
TI  - [Management of insomnia and hypersomnia associated with psychiatric disorders].
AB  - Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic
      disorders are associated with sleep disorders of various kinds, among which
      insomnia is most prevalent and important in psychiatric practice. Almost all
      patients suffering from major depression complain of insomnia. Pharmacological
      treatment of insomnia associated with major depression shortens the duration to
      achieve remission of depression. Insomnia has been recently reported to be a risk
      factor for depression. Hypersomnia is also a major sleep problem in patient
      suffering from depression. There have been no clinical guide to treat the
      symptoms of hypersomnia in depression, but some clinical trials treating them
      with NDRI or adjunctive administration of psychostimulants. In patients with
      schizophrenia, insomnia is often an early indicator of the aggravation of
      psychotic symptoms. Electroencephalographic sleep studies have also revealed
      sleep abnormalities characteristic to mood disorders, schizophrenia and anxiety
      disorders. A shortened REM sleep latency has been regarded as a biological marker
      of depression. Reduced amount of deep Non-REM sleep has been reported to be
      correlated with negative symptoms of schizophrenia. Recently, REM sleep
      abnormalities were found in teenagers having post-traumatic stress disorder after
      a boat accident. Although these facts indicate that insomnia plays an important
      role in the development of psychiatric disorders, there are few hypotheses
      explaining the cause and effect of insomnia in these disorders. Here, we reviewed
      recent articles on insomnia and hypersomnia associated with psychiatric disorders
      together with their clinical managements.

PMID- 21077298
TI  - [Sleep related eating disorder].
AB  - Nighttime eating is categorized as either sleep-related eating disorder (SRED) or
      night eating syndrome (NES). Critical reviews of the literature on both disorders
      have suggested that they are situated at opposite poles of a disordered eating
      spectrum. The feeding behavior in SRED is characterized by recurrent episodes of
      eating after an arousal from nighttime sleep with amnesia. Conversely, NES could
      be considered as an abnormality in the circadian rhythm of meal timing with a
      normal circadian timing of sleep onset. Both conditions clearly concentrate to
      occur during young adulthood, and are often relentless and chronic.
      Misunderstanding and low awareness of SRED and NES have limited our ability to
      determine the exact prevalence of the two disorders. SRED is frequently
      associated with other sleep disorders, in particular parasomnias such as sleep
      walking. Cognitive-behavioral therapy is ineffective, but pharmacotherapy is very
      effective in controlling SRED. Especially, studies have shown that the anti
      seizure medication topiramate may be an effective treatment for SRED.

PMID- 21077299
TI  - [Current topics in prevention, diagnosis and treatment of neuropathic pain from
      different causes: preface and comments].
AB  - Neuropathic pain, as a chronic intractable pain, is well known to be difficult in
      prevention, diagnosis and treatment. Especially, neuropathic pain from different
      causes has each characteristics for prevention, diagnosis and treatment. These
      include post-herpetic pain, persistent chronic pain following traffic accident,
      pain after peripheral nerve injury in venipuncture, phantom limb pain originating
      from dysfunction of the primary motor cortex, pain from failed back surgery
      syndrome, and diabetic neuropathy, and are helpful for understanding prevention,
      diagnosis and treatment of neuropathic pain.

PMID- 21077300
TI  - [Postherpetic neuralgia].
AB  - Varicella-zoster virus (VZV) causes two clinically distinct diseases: varicella
      and herpes zoster. Herpes zoster, recurrent infection of VZV occurs when the cell
      mediated immunity to VZV declines. Since the cell-medicated immunity to VZV
      declines with aging, herpes zoster occurs more frequently in the elderly. Most
      frequent and dreaded complication of herpes zoster is postherpetic neuralgia
      (PHN). The first line of treatment of PHN is medication with tricyclic
      antidipressants and anticonvulsants. Double-blind studies showed that effective
      tricyclic antidepressants for the treatment of PHN are amitriptyline and
      nortriptyline, and effective anticonvulsants gabapentin and pregabalin. When
      tricyclic antidepressant and/or anticonvulsant cannot relieve PHN, opioids should
      be considered in some selected patients. Although neuroablative procedures have
      been performed for the treatment of PHN, their effectiveness was not confirmed by
      double-blind studies. They rather aggravate PHN with time. Recent research with a
      live attenuated varicella vaccine to prevent herpes zoster indicated that the
      vaccine decreased the occurrence of herpes zoster and postherpetic neuralgia by
      almost half as compared with placebo. Vaccination of high risk subjects with the
      varicella vaccine seems to be the most effective measure for the prevention of
      postherpetic neuralgia.

PMID- 21077301
TI  - [Persistent chronic pain following traffic accident].
AB  - Persistent chronic pain in victims injured in traffic accident often results from
      psychological factors to punish the person who caused the accident. Patients with
      whiplash associated disorders sometimes have fear that they can not make full
      recovery from various symptoms including acute or chronic pain. Such a fear
      deteriorates prognosis of the patients as well. Therefore, doctors in charge of
      those patients in emergency room should make effort to subside fear. They should
      not exaggerate seriousness of the injury by overdiagnosis and/or overtreatments,
      but to give correct and adequate information. In addition, in patients with
      complex regional pain syndrome I, psychological dispositions have serious effect
      on prognosis. Although various treatments in pain clinics might be ultimate, they
      are not radical therapeutic procedures that ensure full recovery to daily living
      and social activities. To the patients with CRPS-I, correct diagnosis based on
      the newly established criteria and appropriate treatments in the early stage,
      such as medication of steroids and/or active-passive exercise of extremities in
      alternating hot and cold baths to prevent worsening of chronic symptoms are the
      most essential elements for favorable outcome.

PMID- 21077302
TI  - [Peripheral nerve injury in venipuncture].
AB  - To prevent peripheral nerve injury and neuropathic pain resulting from
      venipuncture, medical students and medical workers should be educated about the
      following points in clinical practice. First, the medial aspect of the
      antecubital fossa should not be punctured, to prevent injury to the median and
      medial anterobrachial cutaneous nerves. Second, the symptoms and signs of
      neuropathic pain resulting from venipuncture should be taught, to recognize the
      onset of neuropathic pain. Third, pharmacotherapy for the management of
      neuropathic pain should be taught to treat neuropathic pain resulting from
      venipuncture.

PMID- 21077303
TI  - [Phantom limb pain originates from dysfunction of the primary motor cortex].
AB  - Accumulated knowledge indicates that phantom limb pain is a phenomenon of the
      central nervous system that is related to plastic changes at several levels of
      the nervous systems. Especially, reports using patients with neuropathic pain
      clearly indicate the sensorimotor cortex as underlying mechanisms of phantom limb
      and its pain. Here, we focus the notion that limb amputation or deafferentation
      results in plasticity of connections between the brain and the body, and that the
      cortical motor representation of the missing or deafferented limb seemingly
      disappears. Meanwhile, the sensory representation of the limb does not disappear
      and thereby patients feel phantom limbs. We propose that dissociation between
      motor and sensory representations in the primary motor cortex induces pathologic
      pain and reconcile of sensorimotor integration of the limb would alleviate pain,
      on the basis of our neurorehabilitation approaches and artificial neuromodulation
      strategies.

PMID- 21077304
TI  - [Failed back surgery syndrome].
AB  - The most confusing point in management of the patients with failed back surgery
      syndrome (FBSS) is that the presence of FBSS is judged not by the objective
      symptom such as neurological deficit evaluated by medical staff but by the
      subjective symptom including feeling of pain, disability and satisfaction on
      medical treatment. In this paper, diagnosis, cause and prevention of FBSS are
      summarized.

PMID- 21077305
TI  - [Management of diabetic neuropathy].
AB  - Inappropriate glycaemic control eventually induces microangiopathy and
      macroangiopathy in diabetic patients. To prevent these complications in
      particular diabetic neuropathy, early intervention to hyperglycemia is the most
      important. Unfortunately, possible methods for treatment of diabetic neuropathy
      are limited at this moment. Main medications for painful diabetic neuropathy are
      targeting to symptomatic cure but not to improvement of pathophysiology of this
      complication. Posttreatment painful neuropathy abruptly appears after acute
      treatment of long-suspended hyperglycemia using drugs and insulin. This self
      limited disease is drug-treatment resistant in many cases. Painful neuropathy is
      sometimes dramatically improved with anti-depressant in case in which the
      patients have masked depression.

PMID- 21077307
TI  - [Remifentanil may be beneficial to urinary output under epidural-based general
      anesthesia].
AB  - BACKGROUND: Remifentanil may be beneficial in patients undergoing abdominal
      surgery by promoting urinary output. METHODS: 258 patients undergoing abdominal
      surgery under epidural-based general anesthesia were assigned to remifentanil
      infusion at 0.05 microg x kg(-1) x min(-1) (Group R, n = 130) or saline (Group N,
      n = 128). General anesthesia was maintained with infusion of propofol (2 mg x kg(
      1) x hr(-1)), vecuronium (60 microg x kg(-1) x hr(-1)) with nitrous oxide (66%),
      and 0.5% levobupivacaine epidural infusion. RESULTS: Patient's demography and
      intraoperative conditions were comparable in both groups. Urinary output was
      larger in Group R (P < 0.0003), and infusion volume was smaller in Group R (P <
      0.0003). CONCLUSIONS: Remifentanil-based general anesthesia increased
      intraoperative urinary output. This phenomenon was observed under epidural
      anesthesia and under low-dose remifentanil infusion.

PMID- 21077306
TI  - [Optimal analgesic effect of continuous supraclavicular brachial plexus block
      with ropivacaine after shoulder surgery].
AB  - BACKGROUND: Optimal dose of local anesthetics for supraclavicular brachial plexus
      block (BPB) is still unknown. We prospectively investigated the analgesic effect
      of ultrasound-guided continuous supraclavicular BPB with ropivacaine at different
      infusion rates. METHODS: Thirty-nine patients scheduled to undergo shoulder
      surgery were randomly assigned to four groups; receiving no continuous BPB
      (control group, n = 10), BPB with 0.2% of ropivacaine at an infusion rate of 4 ml
      x hr(-1) (n = 12), BPB with 6 ml x hr(-1) (n = 12) or BPB with 8 ml x hr(-1) (n =
      5). All patients were permitted to receive nonsteroidal anti-inflammatory drugs
      (NSAIDs) after surgery. Visual analogue scale (VAS) for postoperative pain was
      assessed and frequencies of the requirement of NSAIDs were recorded in each
      group. RESULTS: The pain scores during 24 hours after surgery in the 6 ml x hr(
      1) group (3-24 mm) were significantly lower than those in the 4 ml x hr(-1) group
      (4-42 mm) and control group (6-56 mm). Mean frequency of administrations of
      NSAIDs for 24 hours after surgery in the 6 ml x hr(-1) (0.8 +/- 0.8) group was
      significantly lower than that in the control group (1.7 +/- 1.0). Continuous
      administration in two cases in the 8 ml x hr(-1) group was discontinued due to
      leakage of local anesthetics and headache. CONCLUSIONS: Continuous
      supraclavicular BPB with 0.2% ropivacaine at 6 ml x hr(-1) is effective for the
      pain management after shoulder surgery and is not an excess dose.

PMID- 21077308
TI  - [Retrospective evaluation of dexmedetomidine for postoperative sedation in
      patients for cerebral aneurysm surgery].
AB  - BACKGROUND: Use of conventional sedatives is restricted in order to evaluate
      consciousness levels in patients undergoing intracranial surgery. However,
      patients can become agitated and delirious as a result of insufficient doses of
      sedatives, and as a consequence require physical restriction. Dexmedetomidine
      (DEX) provides a cooperative form of sedation, allowing patients easy transition
      from sleep to wakefulness. The clinical characteristics make it possible to
      perform neurological assessments. We evaluated the effect of DEX for sedation in
      patients undergoing cerebral aneurysm surgery. METHODS: Data were collected
      retrospectively from 49 patients admitted to the ICU after cerebral aneurysm
      surgery who were allocated into two groups: non-DEX(nDEX, n = 25) and DEX (n =
      24). RESULTS: In the nDEX group, two patients were administered sedatives and 10
      patients required physical restriction, as opposed to one in the DEX group (P <
      0.05). Although the Ramsay scale was higher in the DEX group (2.7 +/- 0.6) than
      in the nDEX group (1.5 +/- 0.6) (P < 0.05), there were no significant differences
      on the Glasgow coma scale. CONCLUSIONS: DEX is beneficial for sedation in
      patients undergoing cerebral aneurysm surgery because it provides adequate
      sedation with less physical restriction.

PMID- 21077309
TI  - [The postoperative management of patients after pluropneumonectomy--influence of
      the mode of the operation].
AB  - BACKGROUND: In our hospital, a new mode of operation was introduced in
      pleuropneumonectomy from 2004. We studied how these changes had affected
      postoperative management of patients after pleuropneumonectomy. METHODS: We
      retrospectively reviewed 22 patients who had undergone pleuropneumonectomy for
      malignant pleural mesothelioma from 2001 to 2008. They were divided into two
      groups; those before 2003 (n = 6) and those after 2004 (n = 16). RESULTS: After
      2004, the amount of infusion, amount of blood transfusion and bleeding until POD1
      were less, and the amount of urine output was more than that before 2003. But no
      significant complications were observed. CONCLUSIONS: The new mode of operation
      produced great improvement in immediate postoperative management. It is necessary
      to investigate if the new mode of operation improved prognosis and prevented
      perioperative complications.

PMID- 21077310
TI  - [Inadequate gas supply to the patients after the repair of anesthesia delivery
      system].
AB  - We experienced inadequate gas supply to the patients from the breathing circuit
      of anesthesia delivery system with APL valve at full open position. It was hardly
      noticed after the check-up before starting work with anesthesia delivery system.
      This problem was caused by the mistake in installing the one-way valve when the
      repair of anesthesia delivery system was done. In addition to the check-up before
      starting work, we should check whether gas comes out from the breathing circuit.

PMID- 21077311
TI  - [The reposition of the colon in a patient with Chilaiditi's syndrome after spinal
      operation in the prone position].
AB  - An 82-year-old man with Chilaiditi's syndrome underwent posterior lumbar
      interbody fusion surgery. The colonic gas was in the right lower lung field on
      the preoperative chest X-ray. But 2 years before, his chest X-ray had not been
      diagnosed as Chilaiditi's syndrome. Afterward he had cancer in his left lung and
      the radiation therapy was performed. At this time, after finishing the radiation
      therapy, a spinal operation was planned for his spondylosis. After the operation
      in the prone position, the colonic gas in the right lower lung field disappeared.
      The colon in the subphrenic space was repositioned to the right. The prone
      position may have repositioned the colon in this patient with Chilaiditi's
      syndrome.

PMID- 21077312
TI  - [Airway management using i-gel in two patients for awake craniotomy].
AB  - The i-gel (Intersurgical Ltd., Wokingham, Berkshire, UK) is a new single-use
      noninflatable supraglottic airway device. It is composed of a soft, gel-like,
      transparent, thermoplastic elastomer, which provides a perilaryngeal seal without
      cuff inflation. In this case report, we describe the airway management using i
      gel in two patients scheduled for awake craniotomy. One patient underwent the
      implantation of brain stimulator electrodes and the other patient underwent the
      removal of a glioma near Broca's area. After anesthesia was induced with propofol
      and remifentanil, airway was secured using i-gel. Anesthesia was maintained using
      oxygen, air and propofol, supplemented with an infusion of remifentanil.
      Anesthesia was discontinued after completion of craniotomy. The i-gel was removed
      when patients opened their eyes upon calling their names out. The i-gel was
      reinserted before the closure of the dura without difficulties despite the fact
      that necks were rotated about 30 degrees rightward, and remained in place until
      the end of surgery. All procedures finished uneventfully and without adverse
      events. We conclude that i-gel is effective in asleep-awake-asleep technique
      because of its easiness in reinsertion under condition of rotated neck.

PMID- 21077313
TI  - [Anesthetic management of bilateral PA banding in seven patients with HLHS].
AB  - Regarding the established phased operation for hypoplastic left heart syndrome
      (HLHS), the recent increase in cases involving Fontan operation has led to
      concomitant problems that seem to be caused by invasive open-heart surgery during
      the newborn period. In the new method to overcome this situation, one starts with
      the non-open-heart pulmonic artery banding (bil. PAB) during the newborn period,
      followed by the Norwood-Glenn operation, and finally with the Fontan operation.
      This is a report on seven cases treated with the pulmonic artery banding on HLHS
      at the Nagano Children's Hospital, in which we were personally involved as
      anesthesiologists.

PMID- 21077314
TI  - [Successful management of a patient with myotonic dystrophy under total
      intravenous anesthesia with propofol, remifentnil and rocuronium bromide,
      combined with epidural anesthesia].
AB  - In general anesthesia for a patient with dystrophia myotonica (DM), respiratory
      depression and muscle weakness by opioid, as well as prolongation of the effect
      of muscle relaxant are seen postoperatively. Therefore it is desirable to choose
      agents with short duration of action and to dose these medicines to the minimum.
      We report a case of a 45-year-old woman with DM who underwent laparotomy for
      uterine cancer under general anesthesia combined with epidural anesthesia.
      Epidural catheter was placed from T 11-12, and anesthesia was inducted with
      propofol and remifentanil (RF). We administered rocuronium bromide (RB) 5 mg
      while watching TOF ratio with a muscle relaxation monitor (TOF-Watch). T1 became
      0 after giving a dose of 10 mg, and intubation was performed. We maintained
      anesthesia by propofol and RF combined with epidural anesthesia. TOF ratio was
      restored to around 80% 90 minutes after RB administration, but we did not give
      supplemental doses because the operation went well smoothly. Recovery was smooth
      and fast. The respiratory depression and the muscle spasm were not noticed. RB
      and RE both with short duration of action, are useful in anesthesia management in
      DM cases.

PMID- 21077315
TI  - [Anesthetic management of a patient with acquired factor V inhibitor].
AB  - A 74-year-old man was scheduled for laparoscopic low anterior resection of rectal
      cancer. Preoperative blood coagulation test showed his prothrombin time (PT) and
      activated partial thromboplastin time (APTT) remarkably prolonged. However, he
      experienced only slight epistaxis. Further examination suggested the presence of
      acquired factor V inhibitor. Plasmapheresis was carried out before surgery to
      eradicate inhibitors, but improvement of PT and APTT was temporary. We prepared
      platelet transfusion and recombinant activated factor VII (rFVIIa) for acute
      intraoperative bleeding, but there were no abnormal episodes during the surgery.
      On postoperative day 15, the patient suddenly passed blood in his stool, and
      received platelet transfusion. For the majority of patients with acquired factor
      V inhibitor, bleeding is usually mild, but fatal bleeding complications have also
      been reported. Platelet transfusion was effective in the patient described here.

PMID- 21077316
TI  - [Anesthetic management for PDA in two patients with HLHS stent after bilateral PA
      banding].
AB  - Hypoplastic left heart syndrome (HLHS) is one of the most serious conditions
      among congenital cardiac disorders. In the course of the newly developed phased
      operation, we experienced some cases in which adverse side effects developed due
      to PGE1 preparation. I gave anesthesia in two cases that had to be treated with
      PDA stenting because of the above mentioned side effects.

PMID- 21077317
TI  - [A case report of a ventricular septal defect with congenital portosystemic
      venous shunt].
AB  - A three-month-old baby boy was scheduled for a ventricular septal defect (VSD)
      repair. The patient was complicated with pulmonary hypertension (PH) and
      congenital portosystemic venous shunt (CPSVS). Because it was unclear whether the
      CPSVS was the main cause of the PH or not, the PH was treated with ordinary
      methods for the management of anesthesia for VSD patients with PH. He underwent
      the repair of the VSD, and his postoperative course was uneventful. The mechanism
      of PH in patients with CPSVS is different from that in those with VSD. We
      speculated that his pulmonary arteries were not affected with the CPSVS, because
      no PH was observed after the repair of VSD. Fresh frozen plasma was effective for
      hemostasis during weaning from cardiopulmonary bypass, because he could not
      produce enough coagulation factors.

PMID- 21077318
TI  - [Perioperative management of total laryngectomy for a patient with cold
      agglutinin disease].
AB  - Cold agglutinin disease is possible to cause thromboembolism of various organs
      due to changes in red blood cells by exposure to low temperature. Safety
      standards for perioperative management of patients with cold agglutinin have not
      been established. A patient with cold agglutinin disease was scheduled to undergo
      total laryngectomy and greater pectoral muscle flap. We thought it important to
      perform intensive temperature control to prevent a decrease in temperature below
      the thermal amplitude, which induces agglutinin in the vessel. We tried to keep
      the temperature of the patient with the warming equipment aggressively and
      monitored the shift of temperature in detail. It was also important to shorten
      the surgery with less hemorrhage and anesthetic management which can avoid a
      large shift in body temperature. We could keep peripheral and deep temperature
      above the critical point causing agglomeration. We did not find any symptoms of
      microembolism due to cold agglutination during the operation.

PMID- 21077319
TI  - [Accidental skin burns by fire of an antiseptic agent ignition by the spark of
      electric cautery].
AB  - Surgical fire is a rare complication during the operative period. But, it is a
      severe complication when it occurs. There are antiseptic agents with strong
      inflammability used for skin preparation. We report accidental skin burns caused
      by the spark of electric cautery. The patient was a 29-year-old (50 kg, 158 cm,
      physical status ASA1) woman who underwent laparotomy for acute abdomen.
      Anesthesia was induced and tracheal intubation was performed without trouble.
      Anesthesia was maintained with oxygen, air, remifentanil and sevoflurane. The
      skin of the surgical site was sterilized with an alcoholic antiseptic containing
      chlorhexidine before the operation. Several minutes after the start of operation,
      a fire occurred on using the electric cautery. Immediately, fire was extinguished
      by hands. The cover cloth is peeled off and it was confirmed that the burn
      extended from the right thoracic region to the buttocks. After cooling, it became
      a burn of II to III degrees. Operation was restarted, and at the end, the patient
      was allowed to breathe spontaneously for 5 minutes and extubated afterwards. The
      disinfectant with alcoholic content has a strong inflammability. It is necessary
      to dry it enough before using cautery.

PMID- 21077320
TI  - [Postoperative coil embolization of residual MAPCAs greatly improved left heart
      failure in a patient after corrective surgery for pulmonary atresia, ventricular
      septal defect and MAPCAs].
AB  - A male child, aged 1 year, with pulmonary atresia, ventricular septal defect and
      major aorto-pulmonary collateral arteries (PA, VSD, MAPCA) underwent corrective
      surgery including MAPCA ligation uneventfully. A few hours after admission to the
      ICU, severe heart failure, refractory to aggressive cardiac support including
      epinephrine infusion, became worse. Emergent cardiac catheterization on
      postoperative day 5 demonstrated the residual MAPCA and its occlusion by coil
      embolization dramatically resolved heart failure, indicating that the primary
      cause of this hemodynamic instability was likely excessive left-to-right shunt
      due to MAPCA. Residual LR shunt should be kept in mind to be a rare but
      significant cause of postoperative serious heart failure.

PMID- 21077321
TI  - [Accidental blockage of anesthetic gas scavenging system in ACOMA PRO-45 (ACOMA
      Medical Industry Co, Ltd)].

PMID- 21077322
TI  - [The influence of remifentanil on intra- and postoperative drug cost].
AB  - BACKGROUND: Intraoperative use of remifentanil requires much more analgesics
      postoperatively. Moreover, remifentanil causes intraoperative hypotension and
      bradycardia. METHODS: The objectives are to compare intra- and post-operative
      drug cost between patients who received remifentanil (Group R, n = 72) and those
      who received fentanyl (Group F, n = 66) during laparoscopic cholecystectomy
      retrospectively. RESULTS: The baseline demographics were similar between the two
      groups. Intraoperative drug costs were 7,782 +/- 1,579 yen in Group R and 6,235
      +/- 1,037 yen in Group E Postoperative drug costs were 364 +/- 521 yen in Group R
      and 146 +/- 153 yen in Group E Total drug costs were 8,167 +/- 1,607 yen in Group
      R and 6,381 +/- 1,042 yen in Group E These reached statistical significance (P <
      0.01). Length of hospital stay (days) between the two groups were comparable.
      CONCLUSIONS: Remifentanil anesthesia requires much more intra- and post-operative
      drug cost than fentanyl anesthesia for laparoscopic cholecystectomy.

PMID- 21077323
TI  - [A central monitoring system capturing the screen of an anesthesia monitor].
AB  - e have developed a flexible, economically efficient central monitoring system.
      The system converts RGB analog outputs on the screen of an anesthesia monitor
      display into digital video signals with TwinPact 100 (Thomson Canopus, Kobe), and
      depicts them on the screen of Vidi-installed (http://www.mitzpettel.com/
      software/vidi.php) personal computers (iMac, Apple, Tokyo), which serve as
      terminal monitors. These PCs are monitored and administered through Apple Remote
      Desktop 3 (Apple, Tokyo) on a server computer (Mac Pro, Apple, Tokyo), connected
      to the LAN, in the office for anesthesiologists. As Bosco's Screen Share
      (http://www.componentx.com/ScreenShare/) has been installed on computers in every
      room, we can monitor their screens via a PC in another room using Firefox
      (http://mozilla.jp/firefox/) and other web browsers.The system, with a screen
      capturing function, was designed to comply with all monitor display of all
      medical equipment manufacturers, with possible expansion to the operating rooms.

PMID- 21077324
TI  - [History and current issues of anesthesia in Korea].
AB  - We report the history and current issues of anesthesia in Korea. Korean medical
      doctors have to take 1-year internship and 4-year residency to be qualified to
      take the national examination for a board-certified anesthesiologist. The
      national examination began in 1963, and there were 3,050 board-certified
      anesthesiologists as of 2006. The calculated patients who were managed by a board
      certified anesthesiologist were 5.8 patients a day. The Korean government adopted
      nurse-anesthetists in 1973 because of shortage of board-certified
      anesthesiologists. The Korean Society of Anesthesiologists is now demanding its
      amendment.

PMID- 21077325
TI  - [ADAM8-dependent onset of blood circulation in zebrafish].

PMID- 21077326
TI  - [Regulation of protein ectodomain shedding by nardilysin--a critical role of
      nardilysin in axonal maturation and myelination].

PMID- 21077327
TI  - [ADAM28: involvement in cancer cell proliferation, invasion and metastasis].

PMID- 21077328
TI  - [Multiple discontinuous exosites for von Willebrand factor of ADAMTS13].

PMID- 21077329
TI  - [Role of ADAMTSs in cell migration in the nematode C. elegans].

PMID- 21077331
TI  - [Impacts of ECM dynamics on neuronal remodeling].

PMID- 21077330
TI  - [Molecular mechanism and physiological significance of proteolytic cleavage of
      Reelin].

PMID- 21077332
TI  - [Role of MMP-9 in hematopoietic stem cell niche].

PMID- 21077333
TI  - [Studies on refractory nephrotic syndrome].

PMID- 21077334
TI  - [Epidemiology of nephrotic syndrome].

PMID- 21077335
TI  - [Minimal change nephrotic syndrome].

PMID- 21077336
TI  - [Focal segmental glomerulosclerosis (FSGS)].

PMID- 21077337
TI  - [Membranous nephropathy].

PMID- 21077338
TI  - [Membranoproliferative glomerulonephritis].

PMID- 21077339
TI  - [New insight into nephrotic lupus glomerulonephritis].

PMID- 21077340
TI  - [Diabetic nephropathy and nephrotic syndrome].

PMID- 21077343
TI  - [LDL-apheresis for refractory nephrotic syndrome].

PMID- 21077342
TI  - [Immunosuppressive therapies for refractory nephrotic syndrome].

PMID- 21077341
TI  - [Molecular basis of hereditary nephrotic syndromes].

PMID- 21077344
TI  - [Nutritional factors influencing the incidence of new dialysis due to diabetes
      mellitus in each prefecture of Japan].
AB  - There are regional differences in the incidence of new dialysis in Japan. We
      investigated nutritional factors that might influence the incidence of new
      dialysis due to diabetes mellitus(DM)in each prefecture. We analyzed the data
      reported for 47 prefectures in the National Nutrition Survey 1995-1999 (n =
      38,003), and the Japanese Society for Dialysis Therapy 2005-2007 (n = 45,033).
      Ecological regression was assessed using univariate regression analysis.
      Univariate analysis showed that body mass index (BMI) (r = 0.296, p = 0.022),
      intake of fish and shellfish (r = -0.254, p = 0.043), meat (r = 0.275, p=0.031),
      energy (r = -0.280, p = 0.028), carbohydrates (r = -0.283, p = 0.027), calcium (r
      = -0.278, p = 0.029), iron (r = -0.338, p = 0.010), salt (r = -0.288, p = 0.025),
      vitamin B2 (r = -0.279, p = 0.029), and vitamin C (r = -0.302, p = 0.020) were
      correlated with the incidence of new dialysis due to DM. The incidence of new
      dialysis due to DM in each prefecture may be influenced by environmental factors,
      including nutritional factors.

PMID- 21077345
TI  - [Effects of combination therapy with losartan/hydrochlorothiazide on the
      relationships between base blood pressure, autonomic function, and health-related
      QOL].
AB  - We reported on the relationship between base blood pressure (BP), autonomic
      function and health-related quality of life (HRQOL) in healthy adults. The aim of
      the present study was to examine the relationship between the antihypertensive
      effects, autonomic function, and HRQOL following the treatment of hypertensive
      subjects with losartan/hydrochlorothiazide in hypertensives. In the 10
      hypertensive patients treated with angiotensin receptor blockers for more than 1
      month, combination therapy with losartan/hydrochlorothiazide was conducted for 3
      months after the cessation of treatment with angiotensin receptor blockers.
      Either immediately before the onset of combination therapy or 3 months after the
      treatment, 24-h ambulatory BP and pulse wave velocity (PWV) were measured.
      Sympathetic nervous activity (ratio of low frequency to high frequency component:
      LF/HF) and parasympathetic nervous activity (high frequency component: HF) were
      calculated by heart rate variability. Quality of life (HRQOL) was assessed by the
      Medical Outcome Study Short-Forum 36-Item Health Survey (SF-36). All of the
      participants completed the study. Losartan/hydrochlorothiazide combination
      therapy reduced base BP(from 114 +/- 5 to 100 +/- 3 mmHg; p < 0.03)and 24-h LF/HF
      (from 1.48 +/- 0.18 to 0.94 +/- 0.20; p < 0.02). However, heart rates and PWV
      were not influenced by losartan/hydrochlorothiazide treatment. The HRQOL scores
      improved during the study (p < 0.05). These findings indicated that
      losartan/hydrochlorothiazide was associated with an improvement in base BP
      relative to daytime BP, autonomic function and HRQOL.

PMID- 21077346
TI  - [CCB uptitration is superior to ARB uptitration in CKD patients who do not reach
      target blood pressure with ARB/CCB combined therapy].
AB  - PURPOSE: To evaluate whether a dose increase in angiotensin II receptor blocker
      (ARB) or in calcium channel blocker (CCB) is useful for chronic kidney disease
      (CKD) patients who do not reach their target blood pressure with ARB/CCB combined
      therapy. METHODS: The antihypertensive effect and the influence on the renal
      function were compared by 12 weeks each of a valsartan (VAL) dose uptitration
      period (VAL 160 mg + NCR 20 mg) and a nifedipine CR (NCR) dose uptitration
      period(VAL 80 mg+NCR 40 mg) using a crossover method in 31 CKD patients whose
      blood pressure did not reach the targeted BP with combined therapy with the
      standard dose of VAL 80 mg and NCR 20 mg. RESULTS: The office SBP and early
      morning SBP at 12 weeks after the dose uptitration of NCR were significantly
      lower than the values at 12 weeks after the dose uptitration of VAL. The
      proportion of patients who achieved the targeted BP during the dose uptitration
      period of NCR was higher compared with that during the dose uptitration period of
      VAL. The urinary albumin excretion (UAE) reduced significantly during the dose
      titration period of NCR. However, the reduction of UAE was not significant during
      the dose uptitration period of VAL. The change in eGFR was not observed during
      either of the dose uptitration periods compared with the baseline. Significant
      correlation between the morning BP and UAE was observed during the dose titration
      period of NCR. On the other hand, the correlation was not observed during the VAL
      titration period. CONCLUSION: In hypertensive patients with CKD who do not
      achieve their target BP with ARB/CCB combined therapy, a dose increase of CCB
      would be preferable to that of ARB from the viewpoint of strict control of BP and
      renal protection.

PMID- 21077347
TI  - [Salt intake and the progression of renal failure in patients with chronic kidney
      disease].
AB  - PURPOSE: Salt intake not only elevates the levels of blood pressure, glomerular
      capillary pressure and proteinuria, but also increases oxidative stress within
      the renal cortex in animal models. We examined the effect of salt intake on the
      rate of renal function decline, urinary protein and oxidative stress in patients
      with chronic kidney disease (CKD). METHODS: Clinical data including systolic
      blood pressure (SBP)and diastolic blood pressure (DBP), serum creatinine, uric
      acid, total cholesterol, triglyceride, urinary protein, salt intake, protein
      intake of non-diabetic CKD 53 patients were observed for one year. At the end of
      the observation period, we measured 8-hydroxydeoxy guanosine (8-OHdG) in spot
      urine. We calculated the slope of reciprocal serum creatinine as the rate of
      renal function decline (delta1/Cr). We then investigated the relationship between
      those clinical factors and delta1/Cr, and urinary 8-OHdG, and also selected
      clinical factors that significantly influence delta1/Cr and urinary 8-OHdG by
      stepwise multiple regression analysis. In addition, we investigated the gender
      difference in urinary 8-OHdG. RESULTS: Annual mean SBP and DBP of all patients
      were 121.5 +/- 9.3 mmHg and 72.5+/- 6.2 mmHg, respectively. delta1/Cr was
      negatively correlated with salt intake, urinary protein and urinary protein was a
      significant predictor of delta1/Cr in a multiple regression analysis. Salt intake
      was positively correlated with protein intake and urinary protein. Urinary 8-OHdG
      of all patients was positively correlated with urinary protein and it was a
      significant predictor. Urinary 8-OHdG of male patients was positively correlated
      with salt intake and was a significant predictor; in female patients, it was
      positively correlated with urinary protein and total cholesterol and these two
      factors were significant predictors. CONCLUSION: Salt intake increases urinary
      protein and promotes the progression of renal failure in CKD patients.

PMID- 21077348
TI  - [Association between long-term smoking and hypertension and early-onset nodular
      glomerulosclerosis].
AB  - Diabetic nodular glomerulosclerosis, also known as Kimmelstiel-Wilson syndrome,
      is a specific pathological variant of diabetic nephropathy ; however,
      histological findings similar to diabetic nephropathy are observed occasionally
      without glucose intolerance. Therefore, such nodular glomerulosclerosis is called
      idiopathic nodular glomerulosclerosis. Several case reports that have been
      published recently indicate that smoking and hypertension, which are classical
      renal risk factors, may be attributed to this form of glomerular degeneration.
      Accordingly smoking- and hypertension-associated nodular glomerulosclerosis has
      been considered to be different from the idiopathic form. This novel form of
      nodular glomerulosclerosis is associated with a history of long-term smoking and
      hypertension, and the age of onset of this disease is more than 60 years. We
      present the case of a 27-year-old Japanese male who was admitted to our hospital
      with nephrotic syndrome, hypertension, and renal impairment. He had a smoking
      history of at least 13 years, and had been exposed to passive smoking for several
      years because his parents were smokers. Renal biopsy revealed diffuse and global
      nodular glomerulosclerosis, although the patient did not have any primary
      diseases such as diabetes mellitus or paraproteinemia, that can cause this
      condition. We diagnosed smoking- and hypertension-associated nodular
      glomerulosclerosis. Cessation of smoking and the administration of an angiotensin
      II receptor blocker decreased his proteinuria and showed recovery of kidney
      function. This case report suggests that long-term smoking is closely associated
      with nodular glomerulosclerosis. Further, in our case, the age of the patient was
      lower than that of patients with the same disease among cases that have been
      reported previously.

PMID- 21077349
TI  - [Child neurology, neurology and muscular dystrophy].

PMID- 21077350
TI  - [A fourteen-year-old boy with hyperlordosis, foot drop, mental retardation,
      epilepsy and hearing loss].

PMID- 21077352
TI  - [Epidemiology of subacute sclerosing panencephalitis in Okinawa, Japan (1977
      2005)].
AB  - The epidemiology of subacute sclerosing panencephalitis (SSPE) has changed since
      the introduction of measles immunization in 1970's. We studied the incidence of
      SSPE in Okinawa. There were 22 cases (16 males and 6 females) of SSPE from 1977
      to 2005 in Okinawa. The incidence was 0.63 per million population per year from
      1977 to 1986, 0 from 1987 to 1993, 1.17 from 1994 to 1999 and 0.75 from 2000 to
      2005. Twenty-one SSPE patients had a history of non-immunized measles and 19 of
      them (90%) had measles infection under 2 years of age. There were measles
      epidemic every 2-5 years in Okinawa. Ten of 21 cases contracted measles in 1990
      1991. The percentage of patients with measles infection under 2 years of age
      during measles epidemics ranged from 46% to 56%. Early measles infection (under 2
      years of age) is a risk factor for SSPE. Routine measles immunization to prevent
      measles infection is very important for the prevention of SSPE.

PMID- 21077351
TI  - [Clinical application of the modified Stroop test to children with attention
      deficit/hyperactivity disorder].
AB  - The Stroop test has been already applied to many children with attention
      deficit/hyperactivity disorder (AD/HD). There are, however, differences in the
      measurement of the Stroop test, and also in the background conditions of the
      patients, such as the status of comorbidity with learning disorder (LD),
      medication and the level of Intelligence Quotient (IQ), and presumably as a
      result, the outcome of the Stroop test shows a diversity. This study was
      undertaken to compare the performances of children with AD/HD to normal controls
      using the modified Stroop test according to the subtypes of AD/HD. Subjects in
      this study were 23 unmedicated children with AD/HD, ranging from 6 to 14 years of
      age, and 69 normal controls who were matched on sex and age. Children with AD/HD
      whose verbal IQ and performance IQ were above 80 showed significant differences
      in such indices as Incongruent Color Naming time (ICN) and the resulting index of
      subtracting Color Naming time (CN) from ICN (ICN-CN). As to the analysis
      according to the subtypes excluding 8 cases with comorbid LD, both the
      predominantly inattentive type and the group putting together the predominantly
      hyperactive-impulsive type and the combined type showed significant differences
      in ICN--CN compared with the normal controls. These results suggest that the
      inattentiveness relevant factor affects the performance of the interference task
      in children with AD/HD.

PMID- 21077353
TI  - [Clinical re-evaluation of pediatric inflammatory disorders of the central
      nervous system:a study based on the new classification criteria proposed by the
      International Pediatric MS Study Group].
AB  - A retrospective analysis of the clinical and MRI features in 20 Japanese children
      diagnosed with central nervous system inflammatory demyelinating disorders was
      performed. Using the new criteria proposed by International Pediatric MS Study
      Group, half of children were reclassified into clinical isolated demyelinating
      syndrome (CIS). Presence of seizures and a pattern of diffuse bilateral lesions
      on brain MRIs are more frequent in children with ADEM than in CIS. However we
      suggest these features and encephalopathy may be associated with the age of
      patients. Furthermore, though persistence of abnormal MRI lesions is
      significantly more likely in the group of CIS, none of these patients had a
      subsequent recurrence or developed MS during the follow-up period. The prediction
      of patient prognosis seems to be difficult even based on the new criteria, and
      the nationwide multicenter analysis may be necessary in Japan for acquiring the
      definite conclusion.

PMID- 21077354
TI  - [Relationship between clinical symptoms and Hiragana reading ability in children
      with difficulties in reading and writing:usefulness of a clinical-symptoms
      checklist].
AB  - We investigated the clinical symptoms of children with developmental dyslexia
      (DD) and evaluated the relationship between these symptoms and their Hiragana
      reading abilities. In order to detect the clinical symptoms of DD, we newly
      developed a clinical-symptoms-checklist (CL), which consisted of a total of 30
      yes/no questions regarding symptoms linked to reading (15 questions) and writing
      (15 questions). Subjects were 98 Japanese school grade (1 to 9) children, aged 6
      to 15 years old, with normal intelligence confirmed by the Wechsler Intelligence
      Test for Children (WISC-Ill) and they were divided into 2 groups according to
      their diagnosis. Twenty four children diagnosed as developmental dyslexia
      consisted the DD group, and the remaining 74 children were grouped in the non-DD
      group. CL showed significant construct validity (p<0.05) and inner consistency
      (reading: a =0.82, writing: a =0.72) after deleting two questions from the
      originals. The number of questions checked in the CL reading subcategory
      significantly correlated with the Hiragana reading ability of articulation time
      in all Hiragana reading tasks (p<0.001). More severe clinical symptoms and lower
      reading ability were observed in the DD group compared to the non-DD group.
      Receiver Operating Characteristics (ROC) analysis indicated that these two groups
      could be discriminated by the CL and the results of the reading task, and both
      sensitivity and specificity rate were approximately 80%. It was suggested that 7
      or more positive checks in the CL and 2 or more abnormal scores in the reading
      tasks might discriminate DD from other conditions which cause difficulties in
      reading and writing in Japanese children.

PMID- 21077355
TI  - [Effectiveness of vigabatrin in west syndrome associated with tuberous
      sclerosis].
AB  - Vigabatrin (VGB) is one of the most effective anti-epileptic drugs for tonic
      spasms, those accompanied with tuberous sclerosis complex (TSC), but is not
      available in Japan. We treated 7 patients with West syndrome (WS) and TSC with
      VGB. In these patients, VGB treatment was started at 5-65 months of age. Six
      patients (86%) had complete cessation of tonic spasms. Of these, 3 patients had
      complete cessation within 24 hours after VGB treatment. The mean initial dosage
      of VGB was 36.2 mg x kg(-1) x day(-1), and the mean maintenance dosage was 38.4
      mg x kg(-1) x day(-1). At the beginning of VGB treatment, 3 patients had
      hypsarrhythmia, 2 had focal discharge with generalization, and 2 had only focal
      discharge on electroencephalography. Hypsarrhythmia disappeared within 4-8 weeks
      after VGB treatment. Behavioral problems and sleep difficulty were observed in 6
      patients. Visual field examination revealed no abnormalities in 3 patients. We
      hope that patients with WS and TSC can be treated with VGB as soon as possible in
      Japan.

PMID- 21077356
TI  - [Recurrence of transient splenial lesions in a child with "benign convulsions
      with gastroenteritis"].
AB  - We report a 2-year-old girl who demonstrated "benign convulsions with
      gastroenteritis (CwG)" with transient splenial lesions twice during the winter.
      The first episode was associated with noro-virus and the second with rota-virus.
      During each episode, seizures occurred in clusters without clinical signs of
      dehydration, hypoglycemia, electrolyte derangement or cerebrospinal fluid
      abnormalities, and her consciousness was clear during the interictal period.
      Those findings were consistent with CwG. As transient splenial lesions were not
      accompanied by any neurological abnormalities other than seizures, she was not
      diagnosed as having encephalopathy, but as having CwG. Diffusion-weighted
      magnetic resonance imaging of the brain demonstrated hyperintense lesions in the
      splenium of the corpus callosum, which disappeared within a week. We speculate
      that CwG is likely to lead to transient splenial lesions.

PMID- 21077357
TI  - [Hereditary spastic paraplegia associated with congenital cataracts, mental
      retardation and peripheral neuropathy].
AB  - A 16-year-old male patient was admitted to our hospital with mental retardation
      and a gradually increasing gait disturbance. He fell easily at age 6, and lost
      the ability to jump at age 12. At age 13, he lost the ability to run, and
      developed pes cavus and hammer toes. Spastic paraplegia with mental retardation,
      congenital cataracts, hyper reflexia, dysarthria, callosal hypogenesis and
      peripheral neuropathy were evident at age 16. Laboratory examinations did not
      reveal any underlying disorders. He was diagnosed as having complex spastic
      paraplegia with cataracts, mental retardation and peripheral neuropathy that
      might comprise a genetically distinct entity that is unique to Japan, because all
      prior reports of this combination have been generated only from Japan.

PMID- 21077358
TI  - [Two cases of symptomatic West syndrome suffering from severe respiratory
      syncytial virus-induced bronchiolitis].
AB  - We report two cases of symptomatic West syndrome with severe respiratory
      syncytial virus (RSV)-induced bronchiolitis: one was a 9-month-old boy who was
      hospitalized for shock, and the other was a 15-month-old boy in pre-shock
      condition. Both cases needed mechanical ventilation for approximately 2 weeks.
      Seizures from the primary disease worsened in both patients during the infection,
      and both needed long periods of hospitalization, which resulted in a considerable
      reduction in their quality of life and that of their families. According to a one
      year epidemiological survey of RSV infection conducted in 2004-2005 in Nagano
      prefecture, 7 of 238 hospitalized RSV cases were found to have basic
      neuromuscular disorders. Compared to patients with chronic lung disease or other
      primary diseases, they were older, had higher incidence of mechanical
      ventilation, and required longer hospitalization. Neuromuscular disorders may
      thus be an important risk factor for severe forms of RSV infection. Although
      children with such disorders should be protected from RSV, they are currently
      excluded from the indication for palivizumab administration as passive
      immunization against RSV in Japan.

PMID- 21077359
TI  - [Examination at the sit-down of chair in autism spectrum disorder with children-
      with a pressure weighing device].

PMID- 21077360
TI  - [Stem cells in human amniotic fluid].
AB  - Amniotic fluid (AF) contains a heterogeneous population of cells of fetal origin
      in which stem cells are present. These cells are characterized by their
      expression of mesenchymal (CD73, CD90, CD105) and neural (Nestin, @[beta]3
      tubulin, NEFH) markers, and also some pluripotent markers (Oct4, Nanog), and they
      are capable of differentiating into diverse derivatives in vitro. We have shown
      that epithelial markers are observed in AF stem cells at the same time with
      mesenchymal (Keratin 19, Keratin 18, and p63). During cloning, colonies of cells
      with fibroblastlike and epithelial-like morphologies are formed. The status and
      differentiation potential of stem cells from AF have been discussed.

PMID- 21077361
TI  - [In vitro development of the reconstructed embryos of cattle activated after
      various electrofusion times].
AB  - The dynamics of in vitro development of reconstructed embryos of cattle after
      various electrofusion times was studied. The in vitro mature oocytes without zona
      pellucida enucleated using the touch method were taken as cytoplasts. Fetal
      fibroblasts were used as the nuclei source. Approximately 40% of embryos
      activated between 3 and 3.2 hours after electrofusion developed to blastocysts.
      The effectiveness of in vitro cloned embryo development did not decrease when the
      time between electrofusion and activation was extended up to 4-5 hours. The
      pattern of more successful development of in vitro reconstructed embryos was
      found using enucleated oocytes, excreting the first polar body after 18 hours in
      comparison with oocytes matured in vitro afterwards, as cytoplasts.

PMID- 21077362
TI  - [Muscle regeneration and the state of the thymus in adult rats under laser
      irradiation and alloplasty of the gastrocnemius muscles and diaphragm of newborn
      rats].
AB  - The regeneration of gastrocnemius muscles of adult rats under implantation
      conditions in areas of muscle tissue damage in newborn rats has been studied.
      Alloplasty was performed using minced gastrocnemius and diaphragm muscles, which
      differs at birth in animals by degree of differentiation. The rat-recipient area
      of alloplasty was subjected to He-Ne laser radiation before operation, with the
      aim of reducing the immune response to allogenic muscle tissue. It has been shown
      that the number of regenerating myofibers produced in implanted gastrocnemius
      muscles is more than in alloplants from diaphragms. However, the formation of
      cartilage, bone, and adipose tissue foci were observed in the alloplastic region
      throughout the whole regeneration period. After implantation of minced diaphragm
      muscles, cartilage nodes were observed only in 7-day regenerates. At the end of
      observation, in the first instance, the area of muscle trauma in adult rat
      muscles was replaced by adipose tissue, even in the case of initial laser
      irradiation. During the implantation of diaphragm muscles, the area of trauma was
      filled with regenerating muscle tissue.

PMID- 21077363
TI  - [Investigation of the interaction of repair DNA polymerase beta and autonomous 3'
      --> 5'-exonucleases TREX1 and TREX2].
AB  - The possibility of interaction of recombinant proteins of human repair DNA
      polymerase beta with proofreading 3' --> 5'-exonucleases TREX1 and TREX2 was
      investigated in vitro for the first time. The results of gel filtration analysis
      show the formation of a complex between 3' --> 5' -exonucleases mTREX1 and hTREX2
      and DNA polymerase beta. DNA polymerase activity is shown to increase four-fold
      in the presence of 3' --> 5'-exonuclease TREX2. The experiments with the use of
      immunodot and Western blot assays on the binding of DNA-polymerase beta with 3' -
      > 5'-exonucleases TREX1 and TREX2 immobilized on a nitrocellulose membrane
      provided additional evidence on the direct association of the above proteins in
      complexes.

PMID- 21077364
TI  - [Polymorphism of the cytochrome b gene fragment of mitochondrial DNA of chum
      salmon Oncorhynchus keta (Walbaum) from the Ola River (northern coast of the Sea
      of Okhotsk)].
AB  - Sequencing of 395 bp long fragments of cytochrome b gene occupying the 15396
      15790 bp positions of mtDNA, the data on the structure and variability of the
      studied region in chum salmon from the Ola River (northern coast of the Sea of
      Okhtosk) were obtained for the first time. Nine haplotype variants and four
      protein modifications were obtained. The medial net was built reflecting the
      variability and phylogenetic relationships of haplotypes in the gene pool of the
      studied population of the chum salmon from the Ola River. Comparative analysis of
      the published and original data showed that the Ola chum salmon differs from the
      Canadian salmon ninth genotypically (in structure of cytochrome b gene) and in
      the amino acid sequence of the studied site of the enzyme.

PMID- 21077365
TI  - [Microbial nitrogen fixation in the gastro-intestinal tract of Kalmykia gerbils
      (Meriones. tamariscinus and Meriones meridianus)].
AB  - The nitrogen-fixing activity, nitrogen (N) and carbon (C) contents, and the
      number of microorganisms in the forestomach, cecum, and segmented intestine were
      detected in two gerbil species, granivorous Meriones meridianus and M.
      tamariscinus, which consume a large amount of green parts of the plants. M.
      meridianus had higher levels of nitrogen-fixation activity in all investigated
      parts of the gastro-intestinal tract compared with M. tamariscinus. The highest
      levels were detected in the colon of M. meridianus. The C/N ratios in the
      forestomach of M. tamariscinus were higher than in M. meridianus, which is
      consistent with the greater role of the green parts of plants in its diet. A
      gradual increase in the nitrogen content from the forestomach to the colon of M.
      tamariscinus was noted. The amount of microorganisms in the forestomach and
      intestine of the studied gerbil species was similar.

PMID- 21077366
TI  - [Interspecific hybridization in wild roses (Rosa L. sect. Caninae DC.)].
AB  - Variability of morphological characters and Inter Simple Sequence Repeat (ISSR)
      markers is studied in a mixed multispecies sympatric growth of wild roses in
      Lugansk province of Ukraine. Several methods of data analysis are used, such as
      Principal Coordinates Analysis, cluster analysis (UPGMA), and Bayesian analyses
      of population structure with the Structure 2.2 and NewHybrids programs. The
      results indicate that there are four species growing at the site, viz. R. canina,
      R. villosa, R. dimorpha, and R. podolica, as well as various hybrids between
      them. The hybrid nature of the specimens is confirmed by molecular data, however
      they are not intermediate between the parental species as to their morphology.
      The hybrids either coincide morphologically with one of the parents, or
      demonstrate novel combinations of diagnostic characters.

PMID- 21077367
TI  - [Freezing of dehydrated calluses of spring wheat (Triticum aestivum L.) in liquid
      nitrogen and their morphogenetic potential].
AB  - A cryopreservation method developed earlier was modified for freezing the
      calluses derived from mature embryos of four spring wheat (Triticum aestivum L.)
      pure lines. The effects of individual stages of cryopreservation protocol on the
      water content, number of calluses resuming growth, and rate of morphogenesis were
      analyzed. Growth resumption was observed in 90.5-100% of the calluses after
      dehydration and in 93.3-100% after freezing-thawing. The number of calluses
      displaying signs of morphogenesis considerably decreased after dehydration but
      remained almost the same after freezing-thawing.

PMID- 21077368
TI  - [Conservation of endemic species from the Russian Far East using seed
      cryopreservation].
AB  - A seed response to cryopreservation has been studied in 11 endemic plant species
      from the Russian Far East to determine the possibility of their long-term
      storage. It has been shown that the cryogenic treatment does not kill seeds. The
      viability of 10 species did not decrease (or even increased) after their
      cryogenic storage. We have not revealed any deviations in the development of
      plants germinated from seeds stored at an extremely low temperature (-196 degrees
      C). To monitor germination after long-term storage, procedures of seed
      germination under laboratory conditions have been developed. The results of this
      study contribute to the creation of low-temperature seed banks, able to conserve
      and restore a floral biological diversity.

PMID- 21077369
TI  - [Structure of the mushroom-like bodies in lamellar-antennae beetles (Coleoptera:
      Scarabaeoidea). 1. Basal families and coprophagy Scarabaeoidea].
AB  - Mushroom bodies are in general similarly developed in most taxons studied. The
      calyx region appears as a single structure, and its dual nature is not yet
      realized. An anterio-posterior asymmetry of the calyx region with Kenyon cell
      processes running mostly behind the glomerular neuropil of the calyx is
      characteristic of all the species studied. In this respect, the calyx region of
      basal Scarabaeoidea resembles greatly the calyx of many dipterans. Lobe
      compartmentalization occurs at the initial stage. The passalid beetles represent
      an exception, as their mushroom bodies are much more developed than in related
      families. This may be connected with the complicated social behavior of
      Passalidae.

PMID- 21077370
TI  - [Dynamics of autoimmune myocarditis development in rats].
AB  - The development of autoimmune myocarditis in rats after a single hypodermic
      injection of rat myosin mixed with a complete Freund's adjuvant (CFA) (400
      microg/kg in 200 microl) was studied. The rats from the control group were
      injected with only CFA. The titer of antibodies to myosin, infiltration of
      lymphocytes into the myocardium, ultrastructural damage of myofibrils,
      mitochondria, and nuclei of cardiomyocytes were maximally pronounced on days 14
      21 after the immunization with myosin, which indicates a peak of the inflammatory
      reaction. The content of nitrites and nitrates in the blood serum and myocardium
      of immunized rats were also studied. A certain contribution to the development of
      the inflammation is made by CFA: in rats injected with only CFA, morphological
      signs of myocarditis were found, but to a much lesser degree than in the group
      immunized with myosin.

PMID- 21077371
TI  - [Dynamics of colonies of the speckled ground squirrel (Spermophilus suslicus
      Guld., 1770) on the northern boundary of the habitat].
AB  - Results of studies in 1999-2009 of the dynamics of five isolated colonies of the
      speckled ground squirrel (Spermophilus suslicus) at the northern boundary of the
      habitat of this species (Zaraiskii area, Moscow oblast) are given. An abrupt
      decrease in the number of this species in colonies was established, as was a
      multifold decrease (up to 70-90%) in suitable habitats due to the plowing of
      meadows and build-up of the area. The fragmentation of the optimum habitat of
      ground squirrels reached a stage where colonies can no longer exist as a stable
      autonomous system. The process of their extinction unfolds quickly: the number of
      animals in some colonies decreased five-six times over the last ten years. To
      preserve this species, it is necessary to create areas of steppefied meadows with
      regulated agricultural use.

PMID- 21077372
TI  - [Study of the antiviral activity of cyclopentene beta,beta'-triketone disodium
      salt in the leaves of two Nicotiana tabacum L. cultivars infected with tobacco
      mosaic virus].
AB  - The effect of disodium salt of 2-acetyl-4-hydroxycarbonylmethylthio-5
      chlorocyclopent-4-en-1,3-dione on development of the infection caused by tobacco
      mosaic virus in the leaves of two Nicotiana tabacum L. cultivars--an
      oversensitive cultivar Xanthi-nc and systemically affected Samsun--was studied.
      The results suggest that this compound interferes with reproduction of the virus.
      This antiviral displayed the highest activity when applied in a mixture with the
      virus, presumably due to its action on both the plant and the virus.

PMID- 21077373
TI  - [Hybridization of two mussel species Dreissena polymorpha (Pallas, 1771) and
      Dreissena bugensis (Andrusov, 1897) in natural environment].
AB  - Dreissenids display a high diversity of shell morphology, and it is frequently
      difficult to ascribe some individuals from mixed populations to one of the two
      species, Dreissena polymorpha (Pallas, 1771) or D. bugensis (Andrusov, 1897).
      Presumably, such individuals may be interspecific hybrids. We have analyzed
      species-specific allozyme loci of the typical representatives of these two mussel
      species and putative interspecific hybrids. A natural interspecific hybrid
      between D. polymorpha and D. bugensis was discovered for the first time by
      genetic methods. It has been demonstrated that D. bugensis was a maternal parent.

PMID- 21077374
TI  - [What is science?].

PMID- 21077375
TI  - [Chocoholic part 2; deleted scenes].

PMID- 21077376
TI  - [Trends of the GD monitoring].

PMID- 21077377
TI  - [Calf has knee surgery].

PMID- 21077378
TI  - [Surveillance].

PMID- 21077379
TI  - [Ethics in practice].

PMID- 21077380
TI  - [Blood is living, no blood is dead].

PMID- 21077381
TI  - [A high cell count, problematic?].

PMID- 21077382
TI  - [Is there an need for prosthodontics specialism?].

PMID- 21077383
TI  - [Implants have big disadvantages. Yes].

PMID- 21077384
TI  - [Implants have big disadvantages. No].

PMID- 21077385
TI  - [Patients with unusual requests for extractions 1. professional standard versus
      patient's autonomy].
AB  - Assertive patients will, in the future, more readily appear with their own
      diagnosis. As a result, dentists will more often be confronted with sometimes
      rather unusual requests from patients. An extreme request from a patient is the
      removal of (all) teeth. The central issue in this article is how to deal with
      such a request. The conclusion is that the patient's autonomy is limited by the
      professional standards of the dentist and the patient's capacity to assess in a
      reasonable way what is in his own best interests.

PMID- 21077386
TI  - [Cheilitis angularis].

PMID- 21077387
TI  - [Bipolar disorders and oral health].
AB  - A bipolar disorder is a mood disorder characterized by recurrent occurrences of
      manic, depressive or mixed episodes, separated by shorter or longer relatively
      symptom-free periods. In the Netherlands, the incidence of bipolar disorders is
      1.9%. Bipolar disorders are usually treated with a combination of psycho
      education, self-management and pharmacotherapy. Both the bipolar disorder and the
      drugs for treating this disorder have negative effects on oral health. Patients
      have, among other things, an increased risk of caries, xerostomia, taste
      abnormalities and bruxism. Extensive instruction in oral hygiene, supported
      frequently by professional oral health care, is therefore essential. Considering
      the possible interaction among different kinds of drugs, NSAIDs should only be
      prescribed after consulting the patient's psychiatrist.

PMID- 21077388
TI  - [A woman with ankylosis of the temporomandibular joint].
AB  - A 56-year-old woman was referred to an oral and maxillofacial surgeon because of
      facial stiffness and restricted mouth opening, 13 years after receiving multiple
      mandible fractures in a car accident. After clinical investigation and computer
      tomography, ankylosis of the right temporomandibular joint was diagnosed. The
      patient was treated by means of gap-arthroplasty, in which a myofascial flap of
      the temporalis muscle was used as an interposition transplant. After a period of
      physiotherapy, an acceptable recovery of the mouth opening was achieved.
      Traumatic injury is by far the most prevalent etiology of temporomandibular joint
      ankylosis, followed by an infection of the temporomandibular joint. Treatment
      consists basically of a gap-arthroplasty, with or without interposing a
      transplant between the ramus mandibulae and the joint socket or resection of the
      ankylotic tissues followed by reconstruction of the mandibular caput with an
      autologue transplant or an alloplastic material.

PMID- 21077389
TI  - [Enlargement of the gingiva during treatment with fixed orthodontic appliances].
AB  - Gingival enlargement commonly occurs in patients treated with fixed orthodontic
      appliances. In a study, 25 patients were monitored during and after treatment
      with fixed orthodontic appliances. The extent of the enlargement of the gingiva
      was determined by means of intra-oral photographs made shortly before the
      placement of the appliances, immediately after their removal and at 3 and 6
      months after the appliances had been removed. The enlargement of the gingival was
      determined using a Visual Analogue Scale. During orthodontic treatment the
      average degree of gingival enlargement increased significantly. After removal of
      the appliances a significant decrease in the degree of gingival enlargement
      occurred. Within 3 months after debonding the gingival enlargement was at the
      same level as before starting the orthodontic treatment. The conclusion was that
      the enlargement of the gingiva that takes place during treatment with fixed
      orthodontic appliances was reversible.

PMID- 21077390
TI  - [Consensus on peri-implant infections].
AB  - In 2008, in a workshop of the European Federation on Periodontology, a consensus
      was reached concerning oral peri-implant infections on the basis of the state of
      the art in the relevant sciences. Important conclusions were that peri-implant
      mucositis occurs in 80% of subjects with oral implants, and that peri-implantitis
      occurs in 28-56% of subjects studied. Important risk factors for developing peri
      implant infections seem to be insufficient oral hygiene, a history of
      periodontitis and cigarette smoking. There are insufficient research findings
      available to support a definitive conclusion about the role of genetic factors,
      diabetes mellitus, alcohol consumption and implant surface properties. Mechanical
      treatment in combination with antimicrobial oral mouth rinses may be effective in
      the treatment of mucositis. No evidence has been found that mechanical treatment
      of peri-implantitis is effective. To control the infection of peri-implantitis,
      surgical treatment, often in combination with the use of local or systemic
      antibiotics, is necessary. Validated protocols for the treatment of peri-implant
      infections are not available due to lack of clinical scientific evidence.

PMID- 21077391
TI  - [Compared parasitic infection of Ligula intestinalis (Cestoda: Diphyllobothridae)
      in Cyprinidae species: Rutilus rubilio and Scardinius erythrophthalmus in two dam
      reserves in Tunisia].
AB  - Monitoring quantitative parameters of parasitism by ligula intestinalis (Cestoda:
      Diphyllobothridae) was performed by examining 516 fish belonging to two
      introduced freshwater species: Rutilus rubilio (350 individuals) and Scardinius
      erythrophthalmus (166 individuals). These fish were collected in two dam reserves
      in Tunisia, Sidi Salem and Nebhana. The analysis of the aquatic bird's
      composition in these two reserves revealed the existence of piscivorous bird
      species that were previously reported as final host of Ligula. Monitoring the
      bird's composition highlighted higher relative abundance and frequency in Sidi
      Salem than in Nebhana dam reserve. The analyses of the prevalence, mean intensity
      and abundance of the parasite revealed the most important values in roach,
      Rutilus rubilio which seems to be the preferential second intermediate host of
      the parasite Ligula intestinalis in these environments. Comparative analysis of
      parasitism in both explored sites suggests that Ligula intestinalis presents two
      different strategies of infestation. In Sidi Salem reserve, which is larger than
      Nebhana and containing on important and diversified piscivorous species, the
      parasite infects a maximum of host individuals with low parasite mean intensity
      values. However, at Nebhana, which is a smaller reserve, the parasite infects
      fewer individuals than Sidi Salem but with higher mean intensity. The highest
      prevalence values were recorded in large size classes of roach species in Sidi
      Salem reserve.

PMID- 21077392
TI  - [Eating disorders: the latest in their physiopathology, diagnosis and treatment].

PMID- 21077393
TI  - [Study on cerebral physiopathology in eating disorders by employing multi-channel
      near infrared spectroscopy (photic topography)].

PMID- 21077394
TI  - [Eating disorder associated with developmental dysfunction].

PMID- 21077395
TI  - [Status and treatment of alcohol dependence associated with mental disorders].

PMID- 21077396
TI  - [Cognitive impairment associated with alcohol dependence].

PMID- 21077397
TI  - Evidence-based healthcare in developing countries.
AB  - Developing countries have limited resources, so it is particularly important to
      invest in healthcare that works. The case for evidence-based practice has long
      been made in the West. However, poor access to information makes this endeavour
      near impossible for health professionals working with vulnerable communities in
      low-income economies. This paper provides a call to action to create an evidence
      base for health professionals in developing countries and identify appropriate
      strategies for the dissemination of this information in realistic and meaningful
      ways.

PMID- 21077398
TI  - Antibiotics and antiseptics for venous leg ulcers.

PMID- 21077399
TI  - Benzodiazepines for delirium.

PMID- 21077400
TI  - Bone marrow harvest versus peripheral stem cell collection  for haematopoietic
      stem cell donation in healthy donors.

PMID- 21077401
TI  - Psychosocial interventions for reducing fatigue during cancer  treatment in
      adults.

PMID- 21077402
TI  - [Alcohol dependence and mood disorders].

PMID- 21077403
TI  - [Sleep disorders related to alcohol dependence].

PMID- 21077404
TI  - [Therapeutic trends in alcohol-related disorders].

PMID- 21077405
TI  - [On physiopathology of anxiety disorders: stress-induced fear circuitry
      disorders].

PMID- 21077406
TI  - [New understanding of psychiatric symptoms specific to epilepsy: on an
      international classification (ILAE)].

PMID- 21077407
TI  - Notes from the field: malaria imported from West Africa by flight crews ---
      Florida and Pennsylvania, 2010.
AB  - On September 15, 2010, CDC notified the Florida and Pennsylvania departments of
      health of four Plasmodium falciparum--associated malaria cases among employees of
      a single commercial airline. All four employees had traveled to Accra, Ghana,
      during August 25-September 2, 2010, two of whom were on the same flight. Their
      duration of stay in Accra ranged from 48 to 80 hours. All had stayed at the same
      hotel and spent time outdoors near the swimming pool, in restaurants without air
      conditioning, and in other locations during the evening and night.

PMID- 21077408
TI  - Prevention of coercion in public  mental health care with family  group
      conferencing.

PMID- 21077409
TI  - Pilot study of the efficacy of an  educational programme to reduce  weight, on
      overweight and  obese patients with chronic  stable schizophrenia.

PMID- 21077410
TI  - ACOG Practice Bulletin No. 11: Medical management of endometriosis.

PMID- 21077411
TI  - Impaired laryngeal mobility and entrapment neuropathies.
AB  - Entrapment neuropathies are rarely mentioned in phoniatrics because a definite
      diagnosis is very difficult to make. However, several clinical examples described
      here strongly support this etiology, which should now be considered in the
      diagnosis of both partial and complete laryngeal immobility as well as in minor
      neuromuscular disorders.

PMID- 21077412
TI  - The "Deglutition Handicap Index" a self-administrated dysphagia-specific quality
      of life questionnaire: temporal reliability.
AB  - OBJECTIVE: The aim of this study is to contribute to the psychometric validation
      of the self-administrated dysphagia-specific quality of life questionnaire, the
      Deglutition Handicap Index. Created on the model of the "Voice Handicap Index".
      this questionnaire consists of 30 statements on deglutition related aspects in
      daily life (5 point-rating scale). It is subdivided in three domains of 10 items:
      physical (symptoms), functional (nutritional and respiratory consequences) and
      emotional (psychosocial consequences). MATERIAL AND METHOD: 57 patients were
      included suffering of any kind of swallowing disorders. 17 questionnaires were
      eliminated because 1 to 3 items were not anchored. A test retest performed in an
      interval of 2 weeks, allowed the measure of the intraclasse correlation
      coefficient and the limits of agreement with Bland and Altman graphics. RESULTS:
      The intraclasse correlation coefficient was respectively 0.77 (0.64-0.90), 0.87
      (0.79-0.94), 0.90 (0.84-0.96), 0.91 (0.85-0.96) for the Physical, Functional,
      Emotional and Total Scores. The limits of agreement are 9 points for the
      subscales and 20 points for the total score. CONCLUSION: The DHI has been
      validated in term of content, concurrent and construct validity. The reliability
      was satisfied in term of internal consistency. It is now validated for the
      temporal reliability. The DHI is the solely specific quality of life
      questionnaire related to deglutition available for all kind of oropharyngeal
      swallowing disorders in adults available in clinical practice.

PMID- 21077413
TI  - Temporomandibular dysfunction and dysphonia (TMD).
AB  - Freedom of the manducatory apparatus is critical to economical and accurate vocal
      production. Two types of dysfunction will be discussed: global muscular
      hypertonia of the muscular manducatory system and dysfunction of the
      temporomandibular joint (TMJ). Hypertonia occurs in a high number of dysphonic
      patients. It impairs mandibular mobility and also induces chronic hypertonia of
      the tongue muscles, hyoid apparatus and occipitocervical joint through the
      neuromuscular facilitation process. TMJ can be a major source of mandibular
      kinetics impairment. Its pathogenic effects are most deeply felt in singers, who
      often have their mouths wide open, especially when singing notes in the upper
      register. Affected singers generally use an avoidance or compensation strategy
      which is detrimental to optimal use of resonance cavities and vocal sound
      articulation. It is consequently vital to understand TMJ pathophysiology and to
      include an examination of the manducatory apparatus in any clinical evaluation of
      dysphonia.

PMID- 21077414
TI  - Voice related quality of life after botulinum toxin injection for spasmodic
      dysphonia.
AB  - INTRODUCTION: Laryngeal Focal Dystonia (LFD) leads to a type of voice with a
      strained and tense quality which has a neurological origin, affecting the social
      emotional realms of the individuals, and their quality of life. AIMS: Measure the
      voice-related quality of life of patients with Adductor LFD pre and post
      treatment with Botox, injection followed by voice therapy, using the Voice
      Related Quality of Life (V-RQOL). STUDY DESIGN: Prospective study. METHODS:
      Adductor 11 female patients aged between 33 and 74 years with a diagnosis of
      Adductor LFD were evaluated. All patients underwent a neurological evaluation.
      Laryngoscopy was performed with both rigid and flexible endoscopes. Speech and
      Language evaluation followed the Evaluation of Voice Protocol, proposed by
      Behlau, Pontes (1995). The American V-RQOL measure was utilized. RESULTS:
      Statistical analysis demonstrated significant difference (p < 0.05). 81.8% of
      patients showed higher scores post-Botox, for the social-emotional and physical
      domain. In the overall V-RQOL scores 72.7% of patients showed greater scores post
      treatment. CONCLUSIONS: There was an improvement in the quality of life for these
      patients post-treatment. The V-RQOL proved to be an efficient tool to measure the
      treatment outcomes of LFD pre and post botulinum toxin injection.

PMID- 21077415
TI  - Therapeutic choices for curing dysodia?...three clinical cases.
AB  - These three clinical cases provide an approach to the management of anatomical
      voice disorders. When confronted with a laryngeal diagnosis, talented musicians
      often suffer a crisis of self-confidence which may propel them toward maladaptive
      compensations; these may destabilize their usual techniques, already disrupted by
      the changes in their vocal acoustics. In their forties, each of these patients
      presents with an angiomatous lesion of the vocal fold, associated in two of the
      cases with a congenital structural weakness. For the three of them, the
      recommended therapeutic choice was alternating recorded laryngoscopic follow-up,
      alternative medicine prescriptions, and "artistic sessions" that required that
      their phoniatrician adapt to their repertory, their temperament, the constraints
      of the stage and their laryngeal disorder in order that they achieve a compromise
      between the needs of their career and the laryngeal anatomic realities of the
      moment. These "artistic guidance sessions" are recorded so as to allow the
      patient to become aware of the quality of their public performance and to learn
      the functional elements contributing to it.

PMID- 21077416
TI  - Overdenture retained by teeth using a definitive denture base technique: a case
      report.
AB  - This paper presents a technique involving the use of a definitive denture base to
      make overdentures. Cores with ball attachments were cemented over remaining lower
      teeth. Impressions of the edentulous maxilla and mandible were taken to obtain a
      definitive acrylic resin base. The definitive base of the mandible was perforated
      at the location of ball attachments and its female components were fixed to the
      base using acrylic resin directly in the patient's mouth. Wax rims were then
      made, jaw relationships recorded, teeth mounted and tried in, and the dentures
      were cured. This technique allowed for easy fixing of female components and
      better retention during the recording of jaw relationships, and can also be used
      in the construction of implant retained dentures.

PMID- 21077417
TI  - Effect of post-cure heating on the flexural strength of two indirect resin
      composites.
AB  - The aim of this study was to evaluate whether a post-cure heat-treatment may
      improve the flexural strength of two indirect resin-based composites. Tested
      factors were: material (Gradia Indirect, Gradia Forte), mass (opaqus dentin,
      dentin, enamel) and curing mode (light, light and heat). A three-point bending
      test appliance was developed according to ISO 4049/2000. Three-Way ANOVA and 2
      Pameter Weibull cumulative distribution function were performed. Factors material
      and curing mode were significant (p < 0.001), while the mass type was not (p =
      0.181). A post-cure heat treatment may be useful for enhancing the flexural
      strength of both materials.

PMID- 21077418
TI  - Evaluation of flexural resistance of a denture base acrylic resin reinforced with
      glass fiber and with composite resin.
AB  - The objective of this study was to evaluate the flexural strength of denture base
      resin reinforced with glass fibers and with a laboratorial composite resin. Group
      G1 was formed with specimens made of acrylic resin. Group G2 was formed with the
      same acrylic resin but reinforced with a glass-fiber system, and G3 was
      reinforced with the composite resin. A flexural strength test was performed in
      all groups (n=10). The mean value for the G1 was 86.70 MPa +/- 6.48, for G2 it
      was 86.60 MPa +/- 15.01 and for G3 it was 108.90 + 11.03. The addition of glass
      fiber did not increase the flexural strength however the use of a resin-based
      composite produced significant reinforcement.

PMID- 21077419
TI  - Evaluation of shear bond strength of porcelain bonded to laser welded titanium
      surface and determination of mode of bond failure.
AB  - The aim of this study was to evaluate the shear bond strength of porcelain to
      laser welded titanium surface and to determine the mode of bond failure through
      scanning electron microscopy (SEM) and energy dispersive spectrophotometry (EDS).
      Forty five cast rectangular titanium specimens with the dimension of 10 mm x 8 mm
      x 1 mm were tested. Thirty specimens had a perforation of 2 mm diameter in the
      centre. These were randomly divided into Group A and B. The perforations in the
      Group B specimens were repaired by laser welding using Cp Grade II titanium wire.
      The remaining 15 specimens were taken as control group. All the test specimens
      were layered with low fusing porcelain and tested for shear bond strength. The
      debonded specimens were subjected to SEM and EDS. Data were analysed with 1-way
      analysis of variance and Student's t-test for comparison among the different
      groups. One-way analysis of variance (ANOVA) showed no statistically significant
      difference in shear bond strength values at a 5% level of confidence. The mean
      shear bond strength values for control group, Group A and B was 8.4 +/- 0.5 Mpa,
      8.1 +/- 0.4 Mpa and 8.3 +/- 0.3 Mpa respectively. SEM/EDS analysis of the
      specimens showed mixed and cohesive type of bond failure. Within the limitations
      of the study laser welding did not have any effect on the shear bond strength of
      porcelain bonded to titanium.

PMID- 21077420
TI  - A pilot study examining the effects of enhanced aesthetics on oral health related
      quality of life and patient's satisfaction with complete dentures.
AB  - A randomised cross-over study with a validated assessment tool was used to assess
      patient satisfaction and oral health related quality of life after the delivery
      of two sets of dentures: one set had an enhanced aesthetics. There was a
      significant increase in patient satisfaction and oral health related quality of
      life when baseline data was compared with both types of replacement dentures.
      Some patients preferred the prostheses with enhanced aesthetics, although all
      patients reported significantly increased satisfaction with their new dentures;
      these findings are explored. No difference was seen in the outcome variables
      between the control and aesthetic dentures and sequence of delivery showed no
      difference.

PMID- 21077421
TI  - The use of implants for anchorage in the correction of unilateral crossbites.
AB  - The provision of orthodontic anchorage in the adult patient can be compromised
      due to reduced periodontal support, insufficient number of teeth and limited
      supra-gingival tooth tissue. Where tooth borne anchorage is unavailable for
      significant orthodontic movement implants represent a viable alternative. This
      paper describes the use of dental implants for orthodontic anchorage in a
      partially dentate patient with a severe unilateral cross-bite where orthognathic
      surgery was the only other realistic option. The implants were successfully
      engaged using a composite bridge and a modified quad helix appliance for
      correction of the malocclusion. Once orthodontics was completed the patient was
      restored using highly sintered ceramic crowns and bridges. This paper highlights
      the importance of the multi-disciplinary team and the close liaison between the
      restorative dentist, orthodontist and technician in treatment planning and
      provision.

PMID- 21077422
TI  - Providing support for the pontic of natural tooth adhesive bridges: a clinical
      report.
AB  - Resin bonded bridges have become established as a treatment option for replacing
      missing teeth. Their development can be traced to the work of Rochette who used a
      macro mechanically bonded metal framework to stabilize mobile teeth. Adaptations
      of Rochette's concept, using natural teeth as pontics, have been presented. The
      use of a natural tooth has aesthetic and psychological advantages for the
      patient. The high failure rate of natural tooth pontics may be explained by a
      lack of support for the tooth on the metal framework. A clinical report is
      presented to illustrate a previously unreported technique to improve pontic
      support.

PMID- 21077423
TI  - Effect of some curing methods on acrylic maxillary denture base fit.
AB  - The aim of this study was to investigate the fit of acrylic maxillary denture
      bases processed by the methods of microwave, quick-wet-heat, slow-wet-heat, and
      self curing. Forty stone-casts were obtained using a mould of an undercut-free
      acrylic resin master cast of an edentulous maxilla. Standard acrylic replicas
      patterns sealed on casts and randomized to four groups (10 in each) were used to
      make denture bases using different processing methods for each of the four
      groups. The resultant discrepancy of fit between the denture base and the casts
      were measured using a silicone wafer. Varying fit discrepancies both within and
      between denture base groups was observed. The proportional fit-loss in the
      palatal region was significantly greater than the sulcular areas for all
      materials tested (p < 0.05). The fit-loss observed was greater in microwave-cured
      bases than for other materials examined. Careful selection of appropriate denture
      base materials and processing technique is important when providing complete
      dentures for edentulous patients.

PMID- 21077424
TI  - Absence of carious lesions at margins of glass-ionomer cement (GIC) and resin
      modified GIC restorations: a systematic review.
AB  - This systematic review sought to quantitatively answer the question as to
      whether, in tooth cavities of the same size, type of dentition and follow-up
      period, resin-modified glass-ionomer (GIC) restorations, when compared to
      conventional GIC restorations, offer a significant caries preventive effect, as
      measured by the absence of caries lesions at the margin of restorations. Six
      databases were searched for articles in English, Portuguese or Spanish until 07
      May 2009. Four articles were accepted and 22 separate datasets extracted. The
      difference between both types of material were computed as relative risk (RR)
      with 95% confidence interval (CI). No meta-analysis was undertaken due to aspects
      of clinical/methodological heterogeneity. The results of the extracted datasets
      ranged between RR 0.90 (95% CI 0.81-1.01) and 1.08 (95% CI 0.71-1.63; p > 0.05)
      indicating no difference in the caries preventive effect between both types of
      materials. Further high-quality randomized control trials are needed in order to
      confirm these results.

PMID- 21077425
TI  - Evaluation of the influence of meloxicam and flunixin meglumine on the apoptosis
      of peripheral blood CD4+ and CD8+ T cells in calves.
AB  - The aim of the study was to determine whether treatment with recommended doses of
      meloxicam or flunixin had an effect on the apoptosis of peripheral blood T
      lymphocytes in calves. The study was carried out on 4-5 months old calves (n =
      24, 8 per group). Experimental animals were injected subcutaneously with a single
      dose of 0.5 mg x kg(-1) of meloxicam or intravenously with 3 doses of 2.2 mg x
      kg(-1) day(-1) of flunixin. The non-treatment animals served as control. Blood
      samples were taken at day 0 and at days 1, 2, 3, 5, 7 and 14 after the first
      NSAIDs injection. Apoptosis was determined by flow cytometry using Annexin V-PE/7
      AAD staining. The kinetic analysis of apoptosis in the total lymphocyte
      population, as well as in the CD4+ and CD8+ subsets did not reveal significant
      differences in the frequency of early apoptotic cells between control and
      experimental groups throughout the period studied. Although, 24 h after
      administration of the first dose of NSAIDs, late-stage apoptosis/necrosis was
      significantly increased in the total lymphocyte population (the meloxicam group),
      as well as in the CD4+ (the meloxicam group and the flunixin group) and CD8+ (the
      flunixin group) subsets of T cells. However, this disturbance was transient,
      relatively poorly expressed and, thus, unlikely to be of clinical significance.
      Our results indicate that the use of meloxicam or flunixin in accordance with the
      recommended dosage regimen in cattle do not have a clinically significant
      influence on apoptosis of peripheral blood T cells.

PMID- 21077426
TI  - Analysis of occurrence of virulence genes among Yersinia enterocolitica isolates
      belonging to different biotypes and serotypes.
AB  - The 150 Y enterocolitica strains isolated from humans and from pigs belonged to
      biotypes 4 (68.7%), 1A (18.7%) and 2 (4%), or were biochemically untypeable
      (8.6%). Biotype 4 was comprised of Y. enterocolitica strains representing
      serotype O:3, within biotype 1A the strains either belonged to serotypes O:5 and
      O:6 or were untypeable, and biotype 2 was represented by the strains of serotype
      O:9. The strains which were biochemically untypeable belonged to serotypes O:5,
      O:6 and O:3. Among the strains tested there also were those of an unidentified
      biotype and serotype. Nearly all the strains of biotype 1A represented genotype
      ystB+myfA+, and few belonged to genotype ystB+. The presence of the ystB gene in
      the strains of biotype 1A and only occasional occurrence of the gene in the other
      biotypes makes ystB a distinguishing marker of biotype 1A. The strains of
      genotype ystA+ail+myfA+yadA+ predominated in biotype 4 (serotype O:3). The
      strains of biotype 2 (serotype O:9) represented genotype ystA+ail+myfA+, and the
      plasmid yadA gene was detected in some of them. Within the group of biochemically
      untypeable strains ystB- and myfA-specific PCR products were mainly obtained. The
      genotypes determined for the tested biotypes and serotypes of Y. enterocolitica,
      based upon the selected genes of virulence, can be applied as distinguishing
      markers and indicators of the potential virulence of Y. enterocolitica strains,
      excluding bioserotyping.

PMID- 21077427
TI  - Dynamic changes of immunoglobulin concentrations in pig colostrum and serum
      around parturition.
AB  - The aim of the study was the determination of IgA, IgM and IgG concentrations in
      porcine serum and colostrum, in order to evaluate their variations in the
      perinatal period, as well as to clarify whether there is a correlation between
      colostrum intake, initial level of immunoglobulins (Ig) in piglet serum and
      development of their own immunity. The mean IgA, IgM and IgG concentrations in
      sow serum 10 days before parturition were 1.58, 6.12 and 39.56 mg/ml,
      respectively. Seven days later only the IgG level was insignificantly lower
      (34.94 mg/ml, p = 0.55), while concentrations of IgA and IgM increased to 2.25
      and 7.25 mg/ml, respectively (p = 0.23 and 0.62, respectively). The mean initial
      IgG concentration in colostrum at farrowing was 118.5 mg/ml and differed between
      sows. The average value of IgA in colostrum at birth was 23.8 mg/ml and decreased
      to 7.85 mg/ml at 6 hours (h) and to 4.59 mg/ml at 24 h after the onset of
      farrowing. IgM concentration at birth was 12.1 mg/ml and decreased to 4.23 mg/ml
      at 24 h postpartum. Positive relationships were found between concentrations of
      IgM and IgA in serum of piglets at 14 and 56 days of life (r = 0.41 and 0.80,
      respectively, p < or = 0.05) as well as for IgG concentration in the piglets
      serum at 7 days and 56 days of age (r = 0.48, p < or = 0.05). The above
      observations suggest that there is a correlation between the level of Ig in
      piglet serum in the first days of life and improvement of their own immunity.

PMID- 21077428
TI  - Antibiotic susceptibility of bacteria isolated from respiratory tract of pigs in
      Poland between 2004 and 2008.
AB  - Antibiotic susceptibility of bacteria isolated from nasal swabs and lungs of
      pigs, to 16 commonly used antibiotics, was determined by disc diffusion test.
      beta-lactams showed the best activity against Streptococcus suis (S. suis) (> 99%
      of susceptible strains). The lowest sensitivity of S. suis was evidenced to:
      tylosin, tetracycline and neomycin (50%, 40% and 25%, respectively). Isolates of
      Escherichia coli (E. coli) demonstrated the highest susceptibility to
      cephalosporin (85% strains), gentamicin and norfloxacin (over 74%). The lowest
      susceptibility of E. coli was demonstrated to tiamulin and penicillin (11.3% and
      1.9%, respectively). Over 80% of Actinobacillus pleuropneumoniae (App) strains
      were susceptible to all antibiotics tested. The highest resistance of App, but
      demonstrated by below 20% of tested isolates only, was evidenced to neomycin and
      LxS. Isolates of Pasteurella multocida (Pm), Haemophilus parasuis (Hps) and
      Arcanobacterium pyogenes (A. pyogenes) were highly susceptible to the most
      antibiotics included in the analysis. The comparison of the in vitro
      susceptibility of pathogens to the chemotherapeutics used on Polish farms for the
      therapy of bacterial infection of pigs within the last five years and the last 10
      years, showed an increasing percent of E. coli and S. suis strains resistant to
      commonly used antibiotics. It is also shown that Pm, Hps, App and A. pyogenes
      isolates were continuously susceptible to the most chemotherapeutics applied.

PMID- 21077429
TI  - Phylogenetic analysis of swine influenza viruses isolated in Poland.
AB  - Swine influenza virus (SIV) of H1N1 and H3N2 subtypes are dominated in European
      pigs population. "Classical swine" H1N1 subtype was replaced by "avian-like" H1N1
      subtype. It co-circulates with H3N2 reassortant possessing "avian" genes. In the
      present study, 41 SIV strains isolated from pigs with pneumonia, raised in 20
      Polish farms, were identified and characterised. Since it was evidenced that
      isolates from the same geographic district and the same year of isolation are in
      100% similar, 15 strains representing different district and different year of
      isolation were chosen to construct phylogenetic trees. Two genes, conservative
      matrix 1 (M1) and the most variable, haemagglutynin (HA), were sequenced and
      subjected into phylogenetic analysis. The results of the analysis confirmed that
      "avian-like" swine H1N1 strains evolved faster than classical SIV strains. HA
      gene of these isolates have been derived from contemporary strains of "avian
      like" SIV. In contrast, the M1 gene segment may have originated from avian
      influenza viruses. H3N2 strain is located in swine cluster, in the main prevalent
      European group of H3N2 isolates called A/Port Chalmers/1/73-like Eurasian swine
      H3N2 lineage, which has evolved separately from the human H3N2 virus lineage
      around 1973.

PMID- 21077430
TI  - The efficacy of lactic acid bacteria Pediococcus acidilactici, lactose and formic
      acid as dietary supplements for turkeys.
AB  - A feeding trial was performed on 1400 Big-6 turkey toms divided into experimental
      groups subject to the use of dietary supplements. The ain of this study was to
      evaluate the efficacy of the probiotic supplement Bactocell, containing lactic
      acid bacteria Pediococcus acidilactici, and lactose, administered to turkeys
      separately or in combination, as well as a formic acid supplement. The addition
      of the probiotic under test (lactic acid bacteria Pediococcus acidilactici) to
      diets for turkeys contributed to higher daily gains and lower feed consumption
      per kg weigh gain only during the first 12 weeks of their life. Diet
      supplementation with lactic acid bacteria and lactose reduced mortality rates. A
      slaughter value analysis revealed only a slightly (by approximately 1%) higher
      content of breast muscle and a lower content of thigh muscle in birds fed diets
      supplemented with lactic acid bacteria. Turkeys receiving lactic acid bacteria or
      lactose and a combination of both these supplements were characterized by a
      higher fat content of meat and slightly lower pH values, whereas meat from
      turkeys fed lactose-supplemented diets was darker in color. The addition of
      formic acid Acidum formicum to diets for turkeys contributed only to lower
      mortality rates.

PMID- 21077431
TI  - The role of complement activity in the sensitivity of Salmonella O48 strains with
      sialic acid-containing lipopolysaccharides to the bactericidal action of normal
      bovine serum.
AB  - Sialic acids are important constituents of animal tissue glycoconjugates and are
      also present in the antigens of some bacterial strains. Capsular polysaccharides
      with sialic acid (NeuAc) have been extensively studied with regard to sensitivity
      to the bactericidal action of serum, whereas little is known in this regard about
      lipopolysaccharides (LPS) which contain NeuAc. Strains of Salmonella O48, able to
      infect animals and containing the same structures of LPS with NeuAc, were
      examined for their susceptibility to the bactericidal action of normal bovine
      serum (NBS). The strains showed varied sensitivity to the bactericidal action of
      NBS, which indicates that the expression of LPS containing NeuAc residues is not
      critical for the strains' resistance to the serum's activity. In this study the
      mechanisms of complement activation responsible for killing serum-sensitive
      Salmonella O48 rods by NBS were also established. Three such mechanisms were
      distinguished: activation of the classical/lectin pathways, important (decisive)
      in the bactericidal mechanism of complement activation, parallel activation of
      the classical/lectin and alternative pathways, and independent activation of the
      classical and lectin or the alternative pathway.

PMID- 21077432
TI  - Pathological lesions in European bison (Bison bonasus) with infestation by
      Ashworthius sidemi (Nematoda, Trichostrongylidae).
AB  - Asworthius sidemi Schulz, 1933 is a blood sucking gastrointestinal nematode,
      primarily typical for Asiatic deer. It was found for the first time in Poland in
      European bison in 1997. To estimate the level of invasion of A. sidemi and
      histopathological changes connected with the presence of the parasite in the
      years 2004-2007 parasitological and histopathological examinations of 54 European
      bison from Bialowieza Forest were carried out. Parasitological examination was
      carried out by the sedimentation method and A. sidemi were diagnosed under a
      binocular microscope. Samples for histological examination were collected from
      the abomasum and duodenum walls as well as from regional lymph nodes. Tissue
      samples were then fixed with 10% buffered formalin, embedded in paraffin, cut in
      to 5 microm thick sections and stained with hematoxylin and eosin (H&E).
      Parasitological examinations showed the presence of fourth stage larvae and
      juvenile forms of A. sidemi. The maximal intensity of invasion rose
      systematically from 4470 A. sidemi nematodes in 2004/2005 to 44310 in 2006/2007.
      Histopathological examinations showed infiltrations of inflammatory cells in the
      walls of abomasa and duodena at various levels of intensity (mainly lymphoid
      cells and eosinophils), hyperemiae, oedemae and lesions of mucosa and
      proliferation of lymphatic follicles. In individual cases of dysplasia of
      epithelial cells, atrophy or hyperplasia of glands and the presence of parasites
      in the lumen or walls of the abomasum/duodenum were observed. In one case,
      parasitic nodules were found. In regional lymph nodes proliferation of lymphatic
      follicles, presence of eosinophils and desolation of reproduction centers were
      observed. Intensification of histopathological changes was connected to a
      considerable degree with the developmental stage of A. sidemi as shown by
      parasitological examination.

PMID- 21077433
TI  - Acrosin system of dog spermatozoa and reproductive tract secretions.
AB  - The aim of this study was to determine the activity of proacrosin and acrosin in
      spermatozoa originating from the sperm-rich fractions (SRF) and whole ejaculates
      (WE) of dog semen. In addition, experiments were conducted to determine the
      activity of antitrypsin inhibitors in the fluids of different ejaculate fractions
      and whole seminal plasma. Ejaculates were collected from five dogs of mixed breed
      and one Beagle dog (aged from 2 to 9 years). In the SRF, it was confirmed that
      the activity of the free acrosin form was predominant (acrosin/proacrosin; 2.38
      +/- 0.22/1.05 +/- 0.08 mIU/10(6) spermatozoa). On the other hand, spermatozoa
      originating from the WE exhibited significantly higher (p < 0.05) proacrosin
      activity (proacrosin /acrosin; 2.19 +/- 0.19/1.30 +/- 0.11 mIU/10(6)
      spermatozoa). Furthermore, acrosin inhibitor activity was lower in the fluids of
      the pre-sperm fraction (0.09 +/- 0.006 IU/cm3), whereas it was higher in the
      fluids of the post-sperm fraction (0.11 +/- 0.007 IU/cm3). Using PAGE analysis,
      the antitrypsin activity of the enzyme was represented by the presence of one
      electrophoretic band in the fluids of the pre-sperm and post-sperm fractions and
      whole seminal plasma. Furthermore, two electrophoretic bands were detected in the
      fluids of the SRF. The findings of this study indicate that specific proteinase
      inhibitors present in the individual ejaculate fractions of dog semen may act by
      stabilizing the sperm acrosin system.

PMID- 21077434
TI  - Distribution and amount of cathepsin B in gentamicin-induced acute kidney injury
      in rats.
AB  - The aim of our study was to investigate how the distribution and amount of
      cathepsin B change during acute kidney injury. The research was done on a rat
      model of acute kidney injury that was induced by nephrotoxic antibiotic
      gentamicin. Gentamicin was injected at a dose of 40 mg/kg body weight (the first
      treated group) and 80 mg/kg body weight (the second treated group) for 14 days.
      Control groups received injections of physiological saline only. One day after
      the last injection, animals were euthanized, dissected and kidney samples were
      taken and fixed in 10% buffered formalin. Tissue sections were stained with
      haematoxylin and eosin, periodic Acid Schiff (PAS) and Oil-red-O.
      Immunohistochemistry was used for the demonstration of cathepsin B. Vacuolar
      degeneration of the proximal convoluted tubules was the most prominent pathologic
      lesion found in the first treated group, while necrosis prevailed in the second
      treated group in the same localisation. In both treated groups significantly
      weaker immunohistochemical reaction for cathepsin B was noticed in the proximal
      convoluted tubules in comparison to the control groups (P < 0.05). The decrease
      of positive reaction was the largest in the proximal convoluted tubules of the
      outer renal cortex. Stronger positive reaction for cathepsin B, although not
      statistically significant, was found in the proximal straight tubules (P > 0.05),
      as well. However, more numerous cathepsin B-positive large granules appeared in
      the proximal straight tubules of the second treated group then in the second
      control group (P < 0.05). We can conclude that the amount of cathepsin B in the
      affected proximal convoluted tubules significantly decreases along the increased
      severity of the histopathological lesions of the proximal convoluted tubuls, the
      amount of enzyme in the well preserved proximal straight tubules increases and
      more cathepsin B-positive large granules appear in the cytoplasm.

PMID- 21077435
TI  - The in vitro effect of bovine lactoferrin on the activity of organ leukocytes in
      rainbow trout (Oncorhynchus mykiss), European eel (Anguilla anguilla) and wels
      catfish (Silurus glanis).
AB  - Lactoferrin (LF) is a glycoprotein found in milk, neutrophil granules, secretions
      and selected organs of mammals. Lactoferrin exhibits antibacterial, antiviral,
      fungicidal, immunoregulatory and other functions. Although fish are devoid of
      this protein and its cell receptors, LF effect on the immune mechanisms of fish
      has been demonstrated. The objective of this study was to investigate the effect
      of bovine lactoferrin, applied in vitro, on the activity of head kidney and
      spleen leukocytes in three freshwater fish species: rainbow trout (Oncorhynchus
      mykiss), European eel (Anguilla anguilla) and wels catfish (Silurus glanis). The
      obtained results validate LF beneficial effect on the respiratory burst of
      phagocytes in rainbow trout and wels catfish despite the fact that the potential
      killing activity against Aeromonas hydrophila was not stimulated in any of the
      studied species. Bovine lactoferrin enhanced the proliferation of T-lymphocytes
      in rainbow trout and European eel, as well as of B-lymphocytes in rainbow trout.

PMID- 21077436
TI  - Comparative studies on bone structure in dairy cows with different feeding
      conditions.
AB  - The bone belongs to the dynamic tissues and its structure in domestic cows is
      still not completely understood in correlation to the impact of different food
      components. The aim of our work was a histomorphometrical and immunohistochemical
      research on bone morphology and factors influencing it in healthy dairy cows fed
      with self-produced grain and with rapeseed cakes. The bone of self-produced grain
      fed cows demonstrated statistically significant difference in the number of
      osteocytes from the bone of rapeseed cakes-fed cows. The rapeseed cakes-fed cows
      didn't show any bone cell positive for BMP2/4, while FGFR1 increased
      significantly in their supportive tissues. The number of bFGF- and apoptosis
      containing structures varied in cows of both groups. MMP2 expression showed
      statistically significant difference between both animals' groups with domination
      in bone of cows fed with self-produced grain. Defensin-, osteopontin- and
      osteocalcin-containing cells showed tendency to increase in bone of cows on
      rapeseed cakes diet. Conclusions. The rapeseed-fed cow's long bones demonstrate
      significant decrease of osteocytes per mm2 and selective increase of FGFR1,
      suggesting the (compensatory) growth stimulation in supportive tissue. The
      statistically significant selective absence of MMP2 with a slight tendency of
      increase in osteopontin and osteocalcin in rapeseed-fed cow's long bones
      indicates the persistence of seemingly still compensated qualitative changes in
      bone (beginning of disturbances in mineralization, metabolism etc.) proved also
      by a slight increase of the bone antimicrobial peptide.

PMID- 21077437
TI  - Local effect of progesterone infusion into ovarian artery on activin A and
      inhibin alpha-subunit secretion during the middle luteal phase in gilts.
AB  - The present study was undertaken to elucidate whether an increased, but
      physiological, amount of progesterone (P4) supplied to the porcine corpus luteum
      affects luteal secretion of activin A and inhibin alpha-subunit (Inhalpha) in
      freely moving gilts. On day 9 of the estrous cycle (EC), both ovarian arteries
      and both ovarian veins of gilts (n = 5) were cannulated. Progesterone was infused
      into the right ovarian arteries in gilts on days 10, 11 and 12 of the EC at a
      rate adequate to its physiological retrograde transfer found during the middle
      luteal phase of the EC. The P4 infusion rate was 0.62 microg/min (day 10), 2 x
      0.62 microg/min (day 11) and 3 x 0.62 microg/min (day 12). The left ovarian
      arteries were infused with saline (control). Blood samples were collected from
      both ovarian veins on days 10-12 of the EC before and after P4 or saline
      infusion. The mean plasma activin A level in the ovarian vein ipsilateral to the
      P4-infused ovary was higher (P < 0.0001) on days 10-12 of the EC than this found
      in the contralateral ovarian vein. The level of activin A in the ovarian vein
      ipsilataral to the infusion of P4 was higher on days 11 (P < 0.01) and 12 (P <
      0.0001) and tended to be higher (P < 0.07) on day 10 of the EC than this in
      contralateral ovarian vein. The level of Inhalpha in the ovarian vein ipsilateral
      to the P4-infused ovary on days 10-12 of the EC was not significantly different
      (P > 0.05) than this found in the contralateral ovarian vein. The results of the
      present study indicate that a local elevation of P4 concentration in blood
      supplying the ovary during the middle luteal phase of the porcine EC affects
      ovarian secretion of activin A. The effect of P4 on the secretion of activin A
      suggested the existence of a short regulatory loop of a positive feedback between
      P4 being retrogradely transferred into the ovary and the secretion of this
      peptide.

PMID- 21077438
TI  - The effect of undecanones and their derivatives on tumor angiogenesis and VEGF
      content.
AB  - The in vivo effects of some derivatives of aliphatic ketones (2-undecanone, 3
      undecanone, 4-undecanone and their derivatives) on L-1 sarcoma tumor angiogenesis
      and VEGF content were studied in Balb/c mice. Mice that inhaled 10% solution of 3
      undecanone(3-on) or 1% solution of 2-undecanone propylene acetal (Acpr2) for 3
      days after tumor cells implantation, presented lower neovascular response
      measured by tumor-induced cutaneous angiogenesis test (TIA) and lower tumor VEGF
      content in 5-days tumors, than non-inhaled controls. Other substances presented
      various effects on tumor VEGF concentration and angiogenesis. Histological
      examination of lesions collected from mice inhaled Acpr2, or non-inhaled
      controls, revealed small diffused areas of necrosis in the former group. In both
      groups, slight to moderate inflammatory infiltrations were seen at the tumor's
      margin. In Acpr2 group, there were less small blood vessels at tumor's margin
      than in the control group.

PMID- 21077439
TI  - Seroprevalence of Neospora caninum in free living and farmed red deer (Cervus
      elaphus) in Poland.
AB  - Serum samples from 47 free living and 106 farmed red deer (Cervus elaphus) from
      the Mazurian Lake District in north-east Poland were investigated for the
      presence of antibodies to Neospora caninum. A modified Neospora iscom-ELISA was
      used for initial screening. All sera with optical density (OD) values exceeding
      0.400 absorbance units were further investigated by Western blot analysis.
      Eighteen sera were positive in both tests. Six of these were from free living and
      12 from farmed animals giving prevalence of 13 and 11%, respectively. This is the
      first report of N. caninum infection in farmed and free-living red deer living in
      the same region where neosporosis was confirmed in cattle and the first evidence
      of exposure to the parasite in red deer in Poland.

PMID- 21077440
TI  - Characterization of outer membrane proteins participating in iron transport in
      Pasteurella multocida serotype A3.
AB  - Iron-regulated outer membrane proteins (IROMPs) of P. multocida serotype A3,
      which function as receptors for complexes containing iron ions, are induced by
      iron deficiency in the bacterial growth environment. Analysis of an
      electrophoresis image of proteins isolated from bacteria grown on medium
      supplemented with 2,2'-dipyridyl revealed expression of 16 new proteins that were
      not noted in the case of the bacteria grown in standard conditions, with
      molecular weights from 30 to 160 kDa. Induction of IROMP expression occurred
      within 30 minutes after restricted iron conditions were established. In
      immunoblotting, distinct reactions were noted for proteins of molecular weight
      ranges of 25-49 kDa, 61-95 kDa, and 108-214 kDa. Proteins of the molecular weight
      of 68, 75 and 86 kDa were analysed using mass spectrometry and matched with the
      highest probability to proteins in the NCBI data base. Several dozen different
      proteins with similar amino acid sequences were matched to each sample.

PMID- 21077441
TI  - The influence of experimental Yersinia enterocolitica infection on the pregnancy
      course in sows--preliminary studies. III. Histopathological lesions.
AB  - The aim of the study was to evaluate the anatomo- and histopathological lesions
      in internal organs of sows and their stillborn piglets after experimental Y.
      enterocolitica infection in different phases of pregnancy. Twelve pregnant sows
      were divided into 4 groups, infected per os on 33 (n = 3), 54 (n = 3) and 89 (n =
      3) day of pregnancy with the pathogenic Y. enterocolitica strain isolated from
      the aborted swine fetus, and uninfected control group. Histopathological
      examinations of internal organs and intestine samples of stillborn piglets,
      slaughtered sows and samples of placentas were performed. Anatomo- and
      histopathological lesions were the most intense in the group of sows infected in
      the final phase of pregnancy, where the highest number of stillborn piglets was
      also found. Lesions of internal organs in stillborn piglets suggested a severe
      generalized bacterial infection. Although the analysis of experimental Y.
      enterocolitica infection of pregnant sows revealed that the most intense
      clinical, anatomopathological and histopathological abnormalities were recorded
      in the group of animals infected in the final phase of pregnancy. Infection in
      the first phase of pregnancy could have had an influence on the formation of the
      granulomatous inflammation. Differences in anatomopathological lesions between
      infected and control animals suggest that the period of pregnancy in which the
      infection appears could have had an influence on the course of yersiniosis in
      pigs.

PMID- 21077442
TI  - The effects of genotype and selected environmental factors on colostrum
      production and intake in cattle.
AB  - The aim of this study was to determine effects of genotype and selected
      environmental factors on colostrum production, intake, and efficiency in the
      cattle. The investigations were conducted on 67 dam-calf pairs. All cows were of
      Polish Holstein-Friesian breed, the Black-and-White variety (PHF-HO), whereas
      calves were sired by bulls of the following breeds: PHF-HO, Polish Holstein
      Friesian of the Red-and-White variety (PHF-RW), Jersey (JE), Montbeliarde (MB)
      and Limousine (LI). The colostrum was collected from cows and offered to calves
      "from bucket" thrice a day. The amount of produced colostrum considerably
      exceeded the ability of its consumption by calves. Low share of HF genes in the
      cow, older cow's age and calving in the period from January to April appeared to
      be favorable factors for colostrum production. Calves born to cows with low HF
      gene share drank more colostrum than calves originating from cows with higher
      gene share of this breed. Crosses with JE drank the highest amount of the
      colostrum in relation to body weight, while MB-sired calves drank the highest
      amount in absolute terms. Colostrum intake was positively correlated with the
      dam's age. Furthermore, it was shown that in case of the first colostrum intake
      the most favorable period was from May to September, while in cases of total
      intake in the first day of life and mean intake in the first 5 days of life it
      was the period from January to April. Crosses with JE were characterized by
      extremely high use of colostrum per unit of body weight gain.

PMID- 21077443
TI  - Survival of Corynebacterium pseudotuberculosis within macrophages and induction
      of phagocytes death.
AB  - Since C. pseudotuberculosis is a facultative intracellular pathogen the aim of
      this study was focused on evaluating mechanisms that allowed these bacteria to
      survive in macrophages and determining their influence on induction of cell
      death. The influence of Corynebacteria on the programmed cell death of
      macrophages was determined on the basis of induction the autophagy and apoptosis
      in the cultures of murine macrophage cell lines J774 infected with bacteria.
      Corynebacterium pseudotuberculosis strains could survive within macrophages more
      than 48 hours. During that time bacteria were released as a result of the process
      that lead to death of phagocytes. This property varied among studied strains.
      There was no increase of microtubule-associated protein I light chain 3 (MAP I
      LC3) activity in macrophages infected with examined strains comparing with
      uninfected cultures and cultures treated with autophagy inducer (rapamycin) that
      served as negative and positive controls, respectively. The study with confocal
      microscopy did not show the increasing of caspase-3 activity in the infected
      macrophages and their nucleus did not reveal the fragmentation.

PMID- 21077444
TI  - The effect of exogenous proteases on selected hematological and serum biochemical
      parameters in boars.
AB  - The increasing interest in enzymatic growth promoters prompted this investigation
      of the effect of an enzymatic stimulating complex on selected hematological and
      serum biochemical parameters in boars. The enzymatic complex [five proteases
      (proteinases-endopeptidases) and two peptidases (exopeptidases) obtained by
      fermentation from Streptomyces fradiae] was added to diets for three months, at
      initial doses of 90 (group E1) and 120 (group E2) g/ton feed for the first seven
      days followed by 40 and 60 g/ton, respectively, in the subsequent weeks. The
      evaluation was based on selected hematological (RBC, WBC, HCT (Ht), HGB (Hb),
      MCV, MCH, and MCHC) and biochemical (AST, ALT, AP, Ca, Mg, urea, cholesterol,
      creatinine, inorganic phosphorus, and oxyglucose) parameters determined before
      and after the experimental period. The reported values were within physiological
      norms. Statistical differences were found between experimental groups with
      respect to WBC, HCT (Ht), MCV, MCH, AP, Ca, Mg, creatinine, and inorganic
      phosphorus. The study results indicate that the complex of proteolytic enzymes
      administered to boars caused no negative changes in their metabolic profiles. The
      statistically different hematological and serum biochemical parameters, while
      within normal limits, point to an early stage of microcytic anemia and heightened
      agitation that could be the result of intensified nitrogen metabolism.

PMID- 21077445
TI  - Cytometric analysis of lymphocytes T and B in rabbits infected with non
      haemagglutinogenic strains of RHD virus (rabbit haemorrhagic disease)--Rainham,
      Frankfurt and Asturias.
AB  - The present paper refers to the cytometric analysis of lymphocytes T (with
      receptor CD5+), Th (with receptor CD4+), Tc/Ts (with receptor CD8+), lymphocytes
      CD25+ and lymphocytes B with receptor CD19+ in rabbits experimentally infected
      with strains of RHD virus--Rainham, Frankfurt and Asturias, not having
      haemagglutinogenic capacities, which makes them unique, as haemagglutinogenic
      capacity is a classic and typical property of most strains of this virus. The
      study was performed in the dynamic system, drawing blood samples from animals at
      hour 0, namely before the administration of the viral antigen, and then at 4, 8,
      12, 24 and 36 h after the infection. The study indicated that Rainham and
      Asturias strains of RHD virus cause a similar amount of changes as the most
      immunogenic haemagglutinogenic strains CAMP V-561 and CAMP V-562 of the RHD virus
      do. In contrast, the Frankfurt strain of the RHD virus is characterised with 5-6
      fold lower reactivity in this respect and is most similar to the least
      immunogenic haemagglutinogenic strain CAMP V-558 of the RHD virus.

PMID- 21077446
TI  - Immunomodulating effect of Inter Yeast S on the non-specific and specific
      cellular and humoral immunity in lambs.
AB  - The objective of this study was to determine the stimulating effect of the Inter
      Yeast S dietary supplement on selected parameters of specific and non-specific
      humoral and cellular immunity in lambs. The study involved 32 lambs aged 30 +/- 3
      days, divided into two equal groups: II--control, and II--experimental.
      Experimental group animals were fed a C-J concentrate mixed with a prebiotic, the
      Inter Yeast S, commercially available, containing dried brewer's yeast
      Saccharomyces cerevisiae in the amount of 3 g/kg of the concentrate. At the
      beginning of the experiment (day 0) and on the 15th, 30th and 60th day of the
      study, blood was sampled from the jugular vein to determine selected parameters
      of biochemical, specific and non-specific humoral and cellular immunity in lambs
      (total protein levels, gamma globulin levels, lysozyme activity, ceruloplasmin
      activity, proliferative response of blood lymphocytes (MTT) after stimulation
      with LPS or ConA, the metabolic activity (RBA) and potential killing activity
      (PKA) of phagocytes). As regards humoral immunity parameters, significantly
      higher gamma globulin levels and higher lysozyme and ceruloplasmin activity were
      found in blood serum of experimental lambs administered the Inter Yeast S,
      compared with those determined in control lambs not fed the supplement. No
      statistically significant differences in serum total protein were found between
      the control and experimental groups. An analysis of cellular immunity indicators
      revealed significantly higher levels of RBA and PKA, and higher proliferative
      response of blood lymphocytes (MTT) after stimulation with LPS and ConA in the
      experimental group, compared with those observed in the control group.

PMID- 21077447
TI  - The first description of gastric Helicobacter in free-ranging wild boar (Sus
      scrofa) from Poland.
AB  - Specimens of gastric mucosa of 17 free-ranging wild boars (Sus scrofa) shot in
      the Central Poland during 2007/2008 hunting season were investigated for the
      presence of Helicobacter species. Histopathology, Helicobacter genus-specific 16S
      rRNA PCR, and DNA sequence analysis were employed. In PCR analysis the presence
      of Helicobacter's DNA was detected in one stomach. Obtained sequence analysis
      showed its relatedness to Helicobacter heilmannii type 2. In histopathology of
      the PCR-positive sample the presence of tightly coiled spiral bacteria was
      detected on the surface of the antral mucosa, in gastric pits and lumen of the
      upper parts of antral glands. Potential pathologic significance of the presence
      of Helicobacter in the stomach of free-ranging wild boars was obscured by the
      parasitic invasion-caused gastritis, and remains unknown.

PMID- 21077448
TI  - Prevalence of antibodies against Chlamydophila abortus and Coxiella burnetii in
      goat herds in Poland.
AB  - An epidemiological study was carried out to determine the herd prevalence of
      Chlamydophila abortus and Coxiella burnetii antibodies in goats covered by a milk
      recording program in Poland. The survey took place in 2007 and 48 herds located
      in different parts of the country were involved. A representative sample from
      each herd was taken by a simple random sampling allowing to detect seropositivity
      of a herd on a 95% level of confidence. In total 918 goats were tested for
      specific antibodies against both germs with the use of enzyme-linked
      immunosorbent assays. In addition, history of reproductive failures was recorded
      in these herds. The survey revealed that the herd prevalence of C. abortus was
      4.2% (2 herds) while no C. burnetii antibodies were found. Abortions were
      reported to be a problem in 80% of herds while repeating estrus was encountered
      in 46% of herds. Reproductive failure concerned two seropositive herds as well.
      Since the germ is present in the population, it has to be taken into
      consideration in diagnostic process. Nevertheless, the results of the present
      study indicate that C. abortus infection occurs infrequently in Polish goats. As
      no antibodies against C. burnetii were detected in the screened sample the risk
      of goat-to-human transmission of both bacteria in Poland seems to be very low.

PMID- 21077449
TI  - Effect of Biolex Beta-HP on phagocytic activity and oxidative metabolism of
      peripheral blood granulocytes and monocytes in rats intoxicated by
      cyclophosphamide.
AB  - The objective of this study was to determine the effect of beta-1,3/1,6-D-glucan
      (Biolex-Beta HP) on the phagocytic activity and oxidative metabolism of
      peripheral blood granulocytes and monocytes in rats intoxicated by
      cyclophosphamide. The experimental material comprised 40 adult Wistar rats aged
      14 weeks, divided into two equal groups, a control group and an experimental
      group, each of 20 adult rats, including 10 males and 10 females. In the course of
      3 successive days, 20 rats from the experimental group were administered
      cyclophosphamide intramuscularly at a dose of 50 mg/kg body weight/day. On the
      8th day of the experiment, 10 control group (K) rats and 10 experimental group
      (C) rats were sacrificed. Arterial blood samples were collected and diluted with
      heparin to determine and compare the phagocytic activity (Phatogest) and
      oxidative metabolism (Bursttest) of peripheral blood granulocytes and monocytes
      by flow cytometry. Starting on the 8th day of the experiment, the feed of the
      remaining 10 rats from the experimental group (C+G) and 10 rats from the control
      group (G) was supplemented with Biolex-Beta HP at a dose of 50 mg/kg body
      weight/day for 14 consecutive days. On day 22, arterial blood samples were
      collected from all (C+G) and (C) group rats, diluted with heparin to determine
      and compare the phagocytic activity and oxidative metabolism of peripheral blood
      granulocytes and monocytes by flow cytometry. The results showed that Biolex-Beta
      HP modulated the phagocytic activity and oxidative metabolism of blood
      neutrophils and monocytes suppressed by cyclophosphamide in rats. The
      immunorestoring activity of Biolex-Beta HP was observed in this study.

PMID- 21077450
TI  - Antimicrobial resistance of thermophilic Campylobacter spp. isolated from cattle
      in Poland.
AB  - Campylobacter species are among the most frequently identified bacterial causes
      of human gastroenteritis. Because Campylobacter spp. harbored by cattle can be
      transmitted to humans, in this study we investigated antimicrobial resistance of
      thermophilic Campylobacter isolated from cows. Our study included 150 strains of
      Campylobacter (143 strains of C. jejuni and 7 strains of C. coli) isolated from
      cows in South-Western Poland. The minimal inhibitory concentration (MIC) to
      ciprofloxacin, erythromycin, gentamicin and tetracycline were determined using
      the agar dilution methodology. All strains of C. coli were susceptible to all
      four drugs studied. The most frequently detected resistance of C. jejuni was to
      ciprofloxacin (26 strains 18.2%). Resistance to tetracycline was observed in 5
      strains (3.5%). All strains of C. jejuni were susceptible to erythromycin and
      gentamicin.

PMID- 21077451
TI  - Ultrasonography of the canine shoulder joint and its pathological changes.
AB  - The objective of this study was to present and discuss the available data on
      canine shoulder joint ultrasonography. The paper presents the method of
      ultrasonographic examination of the shoulder joint area, describes the normal
      structure of the shoulder joint in dogs, and discusses the most frequently
      encountered shoulder joint pathologies.

PMID- 21077452
TI  - Septic arthritis in adult horses.
AB  - Septic arthritis in horses is a serious disease which can become life
      threatening. In case the infection can be eliminated before irreversible joint
      damage occurs, complete recovery is possible. This article gives an overview of
      the literature concerning etiology, diagnosis and strategies of therapy in cases
      of septic arthritis in adult horses, with special reference to novel options of
      treatment.

PMID- 21077453
TI  - Application of DNA vaccines in fish.
AB  - Vaccination is a most cost-effective way of controlling infectious diseases in
      fish. However, some vaccination techniques when applied to hatchery conditions
      are not as effective as we expect them to be. Modern molecular biology techniques
      offer a number of opportunities for improving existing bacterial or viral
      vaccines or creating new ones. One of the most promising trends in vaccinology is
      development of DNA vaccination. DNA vaccines are based on the gene encoding
      specific antigen, which is expressed in vaccinated organism and induces the host
      immune system. DNA vaccines, compared to conventional vaccines, have many
      advantages including ability to trigger wider immune response, bigger stability
      and possibility of large-scale production. To date, there are several reports
      indicating effectiveness of DNA vaccines used against fish pathogens.

PMID- 21077454
TI  - Training of potential program implementers of the project P.A.T.H.S. in Hong
      Kong.

PMID- 21077455
TI  - Design of training programs for a positive youth development program: Project
      P.A.T.H.S. in Hong Kong.
AB  - To facilitate the implementation of the Secondary 1 to Secondary 3 program of the
      Project P.A.T.H.S. in Hong Kong, systematic training programs are designed for
      the potential program implementers. The rationales, objectives and design of the
      Secondary 1 to Secondary 3 training programs are outlined in this paper. The
      training programs cover theories of adolescent development, positive youth
      development, background and curricula of the Project P.A.T.H.S., factors
      affecting program implementation quality and evaluation of the project. Besides
      introducing the curriculum units, the training programs also focus on nature of
      learning and related theories (particularly experiential learning), teaching
      methods and instructional techniques, motivating students, and classroom
      management.

PMID- 21077456
TI  - Training potential program implementers of the Project P.A.T.H.S. (Secondary 1
      Program) in Hong Kong.
AB  - To strengthen the implementation quality of the Tier 1 Program (Secondary 1
      Level) of the Project P.A.T.H.S. in Hong Kong, a 20-hour training program is
      provided to the potential program implementers before program implementation. A
      total of 49 workshops were conducted with 2,359 teachers, social workers and
      allied professionals participating in the program. This paper describes the
      objectives, development and implementation of the Secondary One Training Program
      delivered in the first cycle of the P.A.T.H.S. Project. Conceptual and practical
      issues underlying the training program as well as the implications for future
      training programs are also discussed.

PMID- 21077457
TI  - Training for program implementers of Project P.A.T.H.S. in Hong Kong: Secondary 2
      training program.
AB  - Before program implementers implement the Secondary 2 (Grade 8) program of
      Project P.A.T.H.S. in Hong Kong, they are required to participate in a 3-day
      workshop. This paper describes the objectives, curriculum, design and learning
      outcomes of the training program of the 3-day workshop. Three characteristics-
      emphasis on the strengths of the participants, focus on reflective learning and
      utilization of experiential learning--are intrinsic to the training program.
      Through the emphases of the strengths perspectives, experiential learning and
      reflective learning, trainees will appreciate the philosophy and desired teaching
      methodology of P.A.T.H.S.

PMID- 21077458
TI  - Training for program implementers of the Project P.A.T.H.S. in Hong Kong:
      Secondary 3 training program.
AB  - Before the Secondary 3 (Grade 9) program of the Project P.A.T.H.S. is introduced
      into a school in Hong Kong, those responsible for its implementation are required
      to participate in a 3-day workshop. This paper describes the training objectives,
      curriculum, and design of the training program of the 3-day workshop. 'Use of
      self and 'self-disclosure' are two of the major training themes of the program.
      These themes are emphasized repeatedly by the trainers during the workshop. It is
      argued that the open attitude of teachers, together with a genuine sharing of
      their past experiences, would be an effective means of both connecting with
      students and facilitating their reflection and learning during the program.

PMID- 21077459
TI  - Qualitative evaluation of the training program of the Project P.A.T.H.S. in Hong
      Kong.
AB  - A total of 358 participants from 52 schools participated in a 3-day training
      program of the Project P.A.T.H.S. in Hong Kong. At the end of the training
      program, participants were invited to write down what they had learned and their
      experience. A total of 317 written comments were collected from the participants
      in four training workshops. The results showed that most respondents had a
      positive perception of the training program and instructors. Most participants
      felt that the training program enhanced their understanding of positive youth
      development and the project and offered them opportunities for self-reflection.
      Participants showed more confidence in program implementation but also pointed
      out the difficulties in program implementation. This qualitative evaluation study
      provides support for the effectiveness of the training program in the Project
      P.A.T.H.S. in Hong Kong.

PMID- 21077460
TI  - Quantitative evaluation of the training program of the Project P.A.T.H.S. in Hong
      Kong.
AB  - A total of 358 participants from 52 schools participated in a 3-day training
      program of the Project P.A.T.H.S. in Hong Kong. At the end of the training
      program, the participants were invited to respond to a structured subjective
      outcome evaluation questionnaire with 31 items. The results showed that scale and
      sub-scales in the questionnaire were internally consistent. The descriptive
      findings revealed that most of the respondents had positive perception about the
      training program and the instructors. The respondents also felt that the training
      promoted their understanding of the project and encouraged them for self
      reflection. The quantitative evaluation findings echo the qualitative evaluation
      findings suggesting that the training program is effective in promoting the
      participants' knowledge and attitudes about the program and their reflections
      about their teaching efficacy and skills.

PMID- 21077461
TI  - Subjective outcome evaluation of the training program of the Project P.A.T.H.S.
      based on qualitative findings.
AB  - A total of 358 participants from 52 schools joined the 3-day training program of
      the P.A.T.H.S. Project in Hong Kong. At the end of training, participants were
      invited to respond to a subjective outcome evaluation questionnaire (31
      structured items and two open-ended questions). The results based on the
      qualitative analysis of the participants' responses to the two open-ended
      questions showed that participants appreciated the instructors' performance,
      program design and implementation, administrative arrangement, and the ability of
      the training to promote their self-reflection. While suggestions for improvement
      in the training program were noted, the qualitative findings were consistent with
      the quantitative evaluation findings based on the 31 items that the training
      program promoted the participants' knowledge about positive youth development and
      participants' self-reflection, thus supporting the effectiveness of the training
      program for the potential program implementers.

PMID- 21077462
TI  - Medical confidentiality in the late nineteenth and early twentieth centuries: an
      Anglo-German comparison.
AB  - Professional secrecy of doctors became an issue of considerable medico-legal and
      political debate in the late nineteenth and early twentieth centuries in both
      Germany and England, although the legal preconditions for this debate were quite
      different in the two countries. While in Germany medical confidentiality was a
      legal obligation and granted in court, no such statutory recognition of doctors'
      professional secrecy existed in England. This paper is a comparative analysis of
      medical secrecy in three key areas--divorce trials, venereal disease and abortion
      -in both countries. Based on sources from the period between c.1870 and 1939, our
      paper shows how doctors tried to define the scope of professional secrecy as an
      integral part of their professional honour in relation to important matters of
      public health.

PMID- 21077463
TI  - Could the eventual results of the NSABP* 39/RTOG** 0413 trial for partial breast
      irradiation (PBI) be improved by combining spherical applicators and whole breast
      irradiation? Radiobiology suggests it may.
AB  - There may be unacceptable risks associated with the relatively large single doses
      of irradiation prescribed over five days instead of over six weeks for three of
      the four trial arms of the NSABP39/RTOG 0413 clinical trial seeking to enlist
      4,300 patients. The first arm prescribes 60 Gray (Gy) in two Gy fractions over
      six weeks, which is the present standard. The dose implications of the other
      three arms with reference to this standard were examined using the ID2 formalism.
      Particularly poor (non-homogeneous) dose distributions characterise spherical
      applicators like "MammoSite" used as a sole device for accelerated partial breast
      irradiation (APBI). The alternative treatment, APBI done by 3-D conformal
      radiation, may also have a drawback, namely a sudden sharp cut-off in dose which
      may cause cosmetic problems due to circumscribed fibrosis and edema. Some
      recently published results from this trial reveal an alarming level of
      complications. The possible causes of these complications and poor cosmetic
      outcomes and how to avoid them are examined. An obstacle to the more widespread
      use of the "MammoSite type of device is that the device is not allowed closer
      than 5-7 mm from the skin or ribs; a possible remedy for this restriction is
      offered. It is also intended to make the relevant radiobiological principles
      usable for surgical oncologists.

PMID- 21077464
TI  - Management of abnormal cytological findings.

PMID- 21077465
TI  - Hyperthermic intraperitoneal chemotherapy added to the treatment of ovarian
      cancer. A review of achieved results and complications.
AB  - OBJECTIVE: The late revelation of ovarian cancer ensures it as the leading cause
      of death among gynecologic cancers. Cytoreductive surgery (CRS) and intravenous
      (i.v.) chemotherapy have been the cornerstone for a long time to treat this
      disease. More recently, the modality of intraperitoneal administration of
      chemotherapy under hyperthermic conditions (HIPEC) has been added. This review
      surveys the results of HIPEC added to CRS in ovarian cancer. METHODS: A multi
      database search was conducted focusing on mortality, morbidity and overall and
      disease-free (DF) survival rates. RESULTS: 16 studies were identified reporting
      the results of CRS followed by HIPEC of 546 patients with advanced ovarian
      cancer. Postoperative mortality was reported for 14 out of 481 patients in total
      (2.9%). The major morbidity rate varied between 3.4 and 50.0%. In all but one
      study (533 patients), 185 events were reported (34.5%) and 21 re-interventions
      after 476 operations (4.4%). Survival data ranged from 10.0 to 57.1 months for
      the DF survival and from 19.0 to 76.1 months for the overall survival. Optimal
      cytoreduction and recurrent disease were associated with a better outcome in
      selected cases. CONCLUSIONS: Adding HIPEC to the current treatment modalities for
      ovarian cancer seems to be feasible. Improved survival rates have been reported
      at the cost of acceptable mortality rates. Nevertheless, there was a selection
      bias, the morbidity should not be underestimated and it is unclear yet which
      patient will benefit most from this treatment. Randomized controlled trials will
      provide an answer to this question.

PMID- 21077466
TI  - Hormone therapy/adjuvant chemotherapy induced deleterious effects on the bone
      mass of breast cancer patients and the intervention of physiotherapy: a
      literature review.
AB  - In recent years, breast cancer has witnessed some notable improvements regarding
      early diagnosis and new therapeutical strategies, mainly because of the
      utilization of new drugs and systemic treatment protocols, which have had a
      direct impact in the increase of these patients' global survival rate. At the
      same time, it is an ever-growing concern among oncology professionals to identify
      and minimize as much as possible the effects of long-term toxicity resulting from
      cancer therapies. Within this context, physiotherapy fits as a preventive and
      rehabilitating factor regarding functional and skeletal alterations, deriving not
      only from the direct action of breast cancer, but also from the treatment to
      which these patients are submitted. OBJECTIVES: The aim of this study was to
      revise the scientific literature on possible adjuvant chemotherapy-induced
      secondary deleterious effects on the bone mass of patients diagnosed with breast
      cancer, and also to revise the literature on the intervention of physiotherapy in
      cases of secondary bone mass loss caused by adjuvant chemotherapy in patients
      suffering from breast cancer. METHODOLOGY: The research was carried out by
      consulting the following medical websites: Medicus Medline Index, Lilacs,
      Sciello, PubMed (National Library of Medicine), Google Academic and Capes (a
      Brazilian website for scientific information). The selection gathers articles
      written in different languages, English in special, published from January 1998
      to October 2008. RESULTS: 24 studies explicitly mention chemotherapy-induced
      direct and/or indirect effects upon bone mass. Different authors refer to bone
      mass loss as one possible secondary deleterious effect resulting from adjuvant
      chemotherapy applied in breast cancer treatment. Nonetheless, no scientific
      articles were found on the subject of physiotherapy intervention aimed at
      patients in this specific condition. CONCLUSION: The results achieved in this
      revision study point out the possible chemotherapy-induced late deleterious
      effects on patients diagnosed with breast cancer, as well as the additional risks
      for the development of further osteoporotic conditions. Hormone therapy and
      adjuvant chemotherapy treatments may in fact augment and accelerate the loss of
      bone mass, be it directly, through the action of chemotherapeutical drugs, or
      indirectly, through the reduction of estrogenic levels and precocious menopause.
      The scarce material on the rehabilitation of bone mass loss deriving from
      adjuvant treatments reveals, as it seems, a strong need for new studies on the
      subject.

PMID- 21077467
TI  - Molecular markers in epithelial ovarian cancer: their role in prognosis and
      therapy.
AB  - Epithelial cancer of the ovary is the most lethal malignancy of all
      gynaecological cancers. Various clinical and pathological features of ovarian
      cancer are used as predictors of clinical outcome. The use of molecular markers
      in common clinical practice seems promising for the diagnosis and
      prognostication. The aim of this review article is to describe current theories
      regarding the pathogenesis and molecular evolution of epithelial ovarian cancer.
      With respect to the molecules involved, this article focuses on whether they are
      associated with poor prognosis or not. This evaluation is performed in light of
      the progress made and the potential usefulness in treatment decisions without
      overlooking existing controversies that should be further studied. It is tempting
      to anticipate the gradual integration of molecular profiling in clinical
      practice.

PMID- 21077468
TI  - Human papillomavirus (HPV)-type distribution in relation to oral contraceptive
      use in women with cervical intraepithelial neoplasia, Durban, South Africa.
AB  - OBJECTIVE: To determine HPV-type distribution among women with cervical dysplasia
      in relation to oral contraceptive usage. METHODS: Prospective cross-sectional
      study of four groups of patients according to oral contraceptive usage: non
      users, users of less than five years duration, users of between five years and
      ten years, and users of more than ten years duration. Swabs of the cervix were
      analysed for HPV DNA using the polymerase chain reaction method. RESULTS: A total
      of 124 women were recruited for the study. There were 75 patients who were HIV
      infected (seroprevalence 61%). There were 102 patients who were HPV positive
      (82%), of which 79 patients had high-risk HPV DNA (78%). In terms of the four
      oral contraceptive groups, high-risk HPV DNA was detected in 70% (n = 21), 79% (n
      = 22), 90% (n = 21) and 71% (n = 15) of patient, respectively. The odds of having
      HPV DNA was six times higher for the combination of contraceptive users of less
      than five years duration/non-users (OR 5.9, 95% CI: 1.87-18.77). There was no
      change when adjustment was made for age (OR 6.1, 95% CI: 1.9-19.4). HPV DNA type
      16 and/or 18 was present in a total of 21 patients (49%) (non-contraceptive users
      and users < 5 years duration) versus 15 patients (42%) (oral contraceptive users
      of more than 5 years duration) (p = 0.524). HPV type 16 was the commonest HPV
      type detected (20.2%) and HPV type 58 was the next commonest hihg-risk HPV type
      (16.1%). HPV types 58 and 33 were detected in a much greater percentage of our
      population and HPV 16 in a much smaller percentage of our population compared
      with a non-South African population. CONCLUSION: The findings of this study
      demonstrate an interesting distribution of HPV types in a South African
      population.

PMID- 21077469
TI  - A comparison of outcome in patients with stage 1 clear cell and grade 3
      endometrioid adenocarcinoma of the endometrium with and without adjuvant therapy.
AB  - OBJECTIVE: To determine the outcomes in patients with Stage I uterine clear cell
      carcinoma (UCCC) treated with and without adjuvant therapy, and to compare the
      outcomes in these patients to that of matched controls, patients with Stage I,
      grade 3, endometrioid adenocarcinoma of the endometrium (EC). METHODS: Patients
      with FIGO Stage I UCCC who underwent comprehensive surgical staging between
      January 1996 and January 2007 were identified. Cases (UCCC) were matched by age,
      stage, adjuvant therapy, and year of diagnosis to controls consisting of patients
      with grade 3 EC. Recurrence and survival were analyzed using the Kaplan-Meier
      method. RESULTS: 25 patients with Stage I UCCC were identified of whom 13 (52%)
      received no adjuvant therapy and 12 (48%) received adjuvant radiation therapy
      (XRT). The 5-year disease-free survival and overall survival rates for the
      observation and the XRT groups were 78% and 75%, (p = 0.7) and 85% and 82% (p =
      0.1), respectively. When compared to controls, the 5-year disease-free survival
      rates and overall survival rates of patients with Stage I UCCC were not
      significantly different, 77% vs 75% (p = 0.8) and 84% vs 88% (p = 0.5),
      respectively. CONCLUSIONS: In patients with Stage I UCCC tumors there was no
      clear benefit to adjuvant radiation given the absence of improvement in
      recurrence risk or any survival benefit. These data question the benefit of
      radiation therapy in UCCC patients with disease confined to the uterus.

PMID- 21077470
TI  - Liquid based cytology improves the positive predictive value of glandular smears
      compared to conventional cytology.
AB  - PURPOSE: To investigate whether the introduction of liquid-based cytology (LBC)
      in an urban setting decreases the diagnosis of glandular neoplasia (grade 6) and
      improves the positive predictive value (PPV) of cervical cytological screening.
      METHODS: A retrospective database review was conducted identifying women with
      cervical cytological abnormalities including glandular neoplasia (grade 6) before
      and after the introduction of LBC. RESULTS: Following the introduction of LBC the
      rate of glandular neoplasia (grade 6) referrals fell from 1.08% to 0.69% of all
      cervical cytological abnormalities. There was a significant reduction in
      'abnormal' cytological samples subsequently found to be associated with no
      invasive or preinvasive disease but no decrease in the number showing preinvasive
      or invasive disease. A significant decrease in number of patients having a final
      diagnosis of normal/inflammatory or wart changes was seen in those patients
      referred during the LBC period (p < 0.01). CONCLUSION: The introduction of LBC in
      an urban setting decreased cytological glandular neoplasia referrals but not at
      the expense of missing preinvasive and invasive cancers. It has also increased
      the PPV of cervical sampling to detect preinvasive and invasive cancer from 59.6%
      to 76.0%.

PMID- 21077471
TI  - Increase of Mcm3 and Mcm4 expression in cervical squamous cell carcinomas.
AB  - PURPOSE: To examine the relevance of expression of two proteins essential for DNA
      replication initiation, Mcm3 and Mcm4, in cervical squamous cell carcinoma
      (CSCC). METHODS: 53 cases of cervical squamous cell carcinoma, 35 cervical
      intraepithelial neoplasias (CIN) grade 2-3, 11 CIN I and 26 normal controls were
      studied. Immunohistochemistry was performed with anti-Mcm3 and anti-Mcm4
      antibodies. RESULTS: We found Mcm3 and Mcm4 protein expression had a tendency to
      be stronger from control to CSCC. Both Mcm3 and Mcm4 were significantly
      upregulated in squamous cervical carcinoma compared to the control, CIN grade 1
      and grade 2-3 (p < 0.001), and Mcm3 expression was correlated with CSCC cell
      differentiation. However there were no independent prognosis correlations between
      Mcm3 and Mcm4 and clinicopathological parameters including age, stage, tumor
      size, invasive depth and lymph node metastasis. CONCLUSIONS: Mcm3 and Mcm4 were
      highly expressed in CSCC, and these two proteins might be useful as biomolecular
      markers in clinical diagnosis.

PMID- 21077472
TI  - Repeated chemosensitivity testing in patients with epithelial ovarian carcinoma.
AB  - Epithelial ovarian carcinoma (EOC) is a highly chemosensitive tumor, but most
      patients with advanced EOC initially responding to first-line chemotherapy will
      eventually relapse. Chemosensitivity testing may offer an opportunity for the
      optimal selection of chemotherapeutic agents for individual patients. In the
      present retrospective analysis we have examined the changes in chemosensitivity
      profiles during the course of the disease. Chemosensitivity was determined using
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Two
      or more samples at least 14 days apart were obtained from 34 patients with
      ovarian cancer. Chemoresistance increased significantly at the second measurement
      only for paclitaxel and carboplatin, the most frequently used cytotoxic drugs. No
      significant difference compared to baseline was observed at subsequent
      measurements for any other cytotoxic agent studied, although a non-significant
      trend for increased chemoresistance was observed. In conclusion, in the present
      cohort only paclitaxel and carboplatin chemosensitivity changed significantly,
      although to a limited extent, during the course of the disease. In contrast to a
      limited increase of paclitaxel and carboplatin chemoresistance, no significant
      changes were observed for other cytotoxic agents examined. The present data
      indicate that chemoresistance increases, to a modest extent, against the drug
      most frequently used, but remains relatively stable during the course of disease,
      especially for agents that are not used in the therapeutic regimen.

PMID- 21077473
TI  - Non-hormonal treatment of vasomotor symptoms in gynecological cancer patients.
AB  - Gynaecological cancer patients generally suffer from an earlier and more severe
      menopausal syndrome than the general female population. Hormone replacement
      therapy is often contraindicated and there are non-hormonal treatments that are
      proven to be more effective than placebo in randomized controlled trials, e.g.,
      some antidepressants, gabapentine and clonidine. The main limits to the use of
      these drugs in controlling hot flashes are the off-label use for this purpose,
      the very short follow-up and the fact that data come from studies performed on
      breast cancer, not on gynecological cancer patients. Patients believe that drugs
      derived from plants could be effective in relieving hot flashes and that they are
      harmless. Evidence is contrary to this belief and estrogen-sensitive cancer
      patients should be warned of the potential, though very weak, estrogenic effect
      of phytoestrogens and other "natural" drugs, and that their efficacy is close to
      that of a placebo.

PMID- 21077474
TI  - Analysis of clinical and molecular associations of triple negative breast cancers
      in node-negative patients.
AB  - INTRODUCTION: Therapeutic modalities in node-negative breast cancer patients
      remain a matter of controversy. Various prognostic factors have been proposed to
      help select those patients that would most likely benefit from adjuvant therapy.
      In view of this notion the triple negative phenotype (hormone receptors and HER2
      negative tumors) has gained increasing attention. AIM: To evaluate the
      clinicopathologic characteristics of triple negative (TN) tumors in node-negative
      invasive breast carcinomas. METHODS: We retrospectively analyzed the archival
      pathology tissues of 160 patients with node-negative invasive carcinomas,
      diagnosed and treated in two surgical departments in Greece from 1999 to 2006.
      Statistical analysis was used to examine the association between TN tumors and
      other clinicopathological factors. RESULTS: Triple negative breast cancers
      correlated with higher histologic grade, mitotic activation index and Ki-67
      expression (p < 0.05). Moreover TN tumors were correlated with negative staining
      for bcl-2 (p < 0.05). CONCLUSION: In node-negative breast cancer patients, triple
      negativity is associated with aggressive biologic behavior. Further studies are
      required to better understand the clinical implications of these findings.

PMID- 21077475
TI  - Bevacizumab, paclitaxel and carboplatin for advanced ovarian cancer: low risk of
      gastrointestinal and cardiovascular toxicity.
AB  - The purpose of this preliminary study was to retrospectively assess the incidence
      of bowel perforation and hypertension in two separate advanced ovarian cancer
      patient populations following first-line therapy, comprising paclitaxel,
      carboplatin and bevacizumab. The first 20 patients were treated with six cycles
      of paclitaxel (175 mg/m2), carboplatin (AUC of 5 i.v.), and bevacizumab (15 mg/kg
      of body weight); q21 days per an independent protocol. The subsequent patients (n
      = 12) were administered weekly paclitaxel (80 mg/m2), carboplatin (AUC of 5 i.v.)
      every four weeks, and bevacizumab (10 mg/kg of body weight) every two weeks for
      six cycles according to a separate, independent protocol. Bevacizumab was not
      added to either chemotherapy regimen until cycle 2. In both groups patients who
      achieved a complete response, partial response or stable disease at the
      conclusion of induction therapy received bevacizumab (10 mg/kg) and paclitaxel
      (135 mg/m2) q21 days as maintenance therapy. A total of 170 cycles (median = 6;
      range 3-6) of primary induction chemotherapy, 140 of which contained bevacizumab,
      were administered. Moreover, 206 cycles (median = 9; range 1-12) of maintenance
      chemotherapy have been delivered to 28 patients thus far. There was no incidence
      of GI perforation and only two patients demonstrated clinically significant
      hypertension. Previous studies involving bevacizumab have raised concerns
      regarding bowel perforations and hypertension. However, we did not encounter
      difficulties with either of these complications. While we recognize that the risk
      for bowel perforation remains in the 5-11% range, the study's preliminary results
      suggest that first-line treatment of advanced stage ovarian carcinoma with
      bevacizumab can be safely administered.

PMID- 21077476
TI  - Expression of p16 in serous ovarian neoplasms.
AB  - PURPOSE: We aimed to examine p16 protein expression in ovarian serous neoplasms
      along with normal ovarian tissues. MATERIALS AND METHODS: P16 expression was
      immunhistochemically evaluated in 86 ovarian serous neoplasms (21 cystadenomas,
      20 borderline tumors and 45 carcinomas) and 21 non-neoplastic ovarian tissue. The
      results were also compared with histopathological grade in serous
      adenocarcinomas. RESULTS: P16 expression rates for benign, borderline ovarian
      tumors and ovarian cancer were 14.2%, 85% and 86.6%, respectively. It was
      significantly higher in carcinomas (p < 0.001) and borderline tumors (p < 0.001)
      compared to cystadenomas. No immunoreactivity was found in the non-neoplastic
      ovarian surface epithelial cells. The percentage of p16 expression did not change
      significantly with histological grade in carcinomas. CONCLUSION: P16 expression
      is strong and widespread involving most tumor cells in serous papillary ovarian
      carcinomas, and is probably an early event.

PMID- 21077477
TI  - Distribution of HPV genotypes in uterine cervical lesions among the Uighur women
      in Xinjiang province of China.
AB  - OBJECTIVE: The aim of this study was to investigate the distribution of HPV
      genotypes in uterine cervical lesions of Uighur women in the Xinjiang province of
      China. METHODS: A total of 223 formalin-fixed paraffin-embedded cervical tissue
      specimens from Uighur patients with squamous cell carcinoma (SCC) and cervical
      intraepithelial neoplasia (CIN) were analyzed with HPV specific general primer
      pairs MY09/11 by PCR amplification and HPV chip. RESULTS: Among 223 cases, HPV
      positive samples accounted for 58.7% (131/223). HPV infection rate increased
      along with the pathological grade of the specimens, with a clear tendency of
      normal < CIN 1 < CIN 2 < CIN 3 < SCC. HPV16 infection was the predominate one and
      reached the highest level in SCC with 96%. HPV18 and 58 were detected only in
      some specimens as a second infection in addition to HPV16. The infection rate and
      type of HPV was not closely associated with the histological differentiation of
      the cervical cancer. CONCLUSION: HPV 16 was the most common type detected in
      Uighur women with SCC and CIN in the Xinjiang area of China. Together with the
      high infection rate, this may be the reason for the four-fold higher cervical
      cancer incidence in this province and in this population, when compared to total
      China. The prevalence of HPV18 and 58 was relatively low.

PMID- 21077478
TI  - Intestinal-type metaplasia in the original squamous epithelium of the cervix.
AB  - There have been a number of reports on cervical carcinomas, both invasive and
      intraepithelial (CIN III), indicating the presence of intracellular mucins in the
      absence of glandular differentiation. Yet, the expression of such cells in the
      normal/original squamous epithelium of the cervix remains unexplored. We
      investigated the presence of mucin-distended goblet cells at this site, after
      examining retrospectively normal cervices from 250 hysterectomy specimens. Goblet
      cells were detected in 3.2% (8/250) of the cervices examined using haematoxylin
      and eosin stained sections and confirmed by mucin histochemistry: alcian blue
      (AB) pH 2.5, periodic acid-Schiff reaction with and without diastase digestion
      (PAS-d, PAS) and the combined AB/PAS. Additional sections were stained with Diazo
      and Masson-Fontana for argentaffin granules and Grimelius for argyrophil cells,
      but were all negative and no other cell types were identified. It is believed
      that this incomplete type of intestinal metaplasia is an acquired change in the
      cervix, derived from multi-potential stem cells of Mullerian duct origin.

PMID- 21077479
TI  - Evaluation of preoperative diagnosis with results of histopathological
      examinations of ovarian tumors in women of reproductive age.
AB  - Ovarian tumors are the most frequent lesions encountered by gynecologists.
      Ovarian carcinoma most often develops asymptomatically and until now no
      sufficient screening diagnostic methods have been developed, which is why various
      diagnostic methods are being tried concurrently to increase diagnostic
      sensitivity. The aim of this paper was to evaluate the compliance of the
      preoperative diagnoses with the results of histopathological examinations of
      ovarian tumors and to determine the usefulness of simultaneous application of
      gynecological, ultrasonographic, and Doppler examinations together with
      determination of CA-125 antigen in the diagnostic process of ovarian tumors. The
      study comprised a group of 250 women in reproductive age who were operated on for
      tumors of the ovary. Results of histopathological examinations were compared with
      the preoperative diagnosis based on the above-mentioned examinations and
      prognostic indicators: sensitivity, specificity, negative and positive prediction
      value as well as accuracy were determined. The results showed that combining the
      four diagnostic methods is a useful research panel in the preoperative diagnostic
      process of ovarian tumors and makes selecting the appropriate procedure and
      surgical treatment viable.

PMID- 21077480
TI  - Management of recurrence from a retroperitoneal xanthogranuloma: case report.
AB  - Xanthogranulomas from the retroperitoneal space are rare. To our knowledge only a
      few cases have been reported in the literature in the retroperitoneal space. In
      this report, the authors present the case of a 24-year-old woman with a
      recurrence of this rare tumor. Two years after resection, the mass showed rapid
      local recurrence. Attention should be paid to the possibility of the
      transformation into a fibroxanthosarcoma, which could have an aggressive clinical
      course.

PMID- 21077481
TI  - A benign metastasizing leiomyoma involving a nodule in the pulmonary artery: case
      and literature review.
AB  - Benign metastasizing leiomyoma (BML) is a rare disease defined as a primary
      benign uterine tumor with "metastatic" lesions preferentially occurring in the
      lung, pelvis and lymph nodes. There are few reports about local recurrence after
      initial surgery. We report a case of a BML with local recurrence and metastasis
      growing into the wall of the left pulmonary artery, diagnosed 11 years after
      initial hysterectomy. A 55-year-old woman complaining of abdominal discomfort,
      heaviness and asthenia was admitted to our hospital for investigation of a
      voluminous uterine mass with high vascularization and three pulmonary nodules.
      The resection of the mass by laparotomy was complicated by uncontrolled severe
      hemorrhage due to vascular proliferation, requiring multiple transfusions,
      packing the cavity and postoperative uterine artery embolization. Three months
      later the patient underwent a left upper lobe lobectomy with the aim of removing
      the largest pulmonary nodule, a nodule a located in the lingular branch of the
      left pulmonary artery. The comparison of hysterectomy and lobectomy pieces showed
      a similar aspect, leading thus to the diagnosis of BML. Awareness of this rare
      entity should potentially avoid under-diagnosis and difficulties due to
      hemorrhage during surgery.

PMID- 21077482
TI  - Metastatic and recurrent adenocarcinoma of the uterine cervix: a long-term
      survival of 16 years.
AB  - PURPOSE OF INVESTIGATION: Recurrent metastatic adenocarcinoma of the cervix is
      associated with an extremely poor prognosis. Treatment options for recurrent
      disease are limited and cure is extremely rare. CASE REPORT: We report a case of
      a 43-year-old patient with Stage IB adenocarcinoma of the cervix. She had
      multiple metastatic recurrence episodes salvaged with several radical surgeries,
      external and intraoperative irradiation, and chemotherapy over a survival period
      of 16 years. CONCLUSION: We conclude that long-term multi-modal salvage treatment
      may achieve longer survival in rare cases with recurrent metastatic
      adenocarcinoma of the cervix.

PMID- 21077483
TI  - Three-dimensional power Doppler color ultrasonographic features of a minimal
      deviation adenocarcinoma of the uterine cervix.
AB  - A case of minimal deviation adenocarcinoma of the cervix in a 34-year-old female
      is presented. The ultrasonographic and three-dimensional power Doppler color
      studies revealed a nodular cervical lesion with vascularization more prominent in
      the center of the nodule but also present at the periphery. The imaging diagnosis
      was suggestive of a myoma but with more vascularization than a conventional one.

PMID- 21077484
TI  - Ovarian metastasis of a primary renal cell carcinoma: case report and review of
      literature.
AB  - Ovarian metastases from renal cell carcinoma (RCC) are very rare, with only 23
      cases reported in the literature. We report a case of 54-year-old women who
      developed bilateral ovarian metastasis 39 months after diagnosis of clear cell
      carcinoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was
      carried out. Subsequently she was treated with sunitinib and her disease
      stabilized. She is still alive four years after diagnosis of the renal primary,
      and disease has stabilized on sunitinib. We conclude that, although rare, the
      possibility of metastatic RCC should be considered in the differential diagnosis
      of clear cell tumors of the ovary. Due to therapeutic and prognostic
      implications, it is very important to differentiate if the tumor is a primary
      ovarian tumor or a metastasis from a renal cell carcinoma. Early diagnosis of
      this rare metastatic tumor results in prompt treatment and prolonged patient
      survival.

PMID- 21077485
TI  - Liver resection for metastases arising from recurrent granulosa cell tumour of
      the ovary--a case series.
AB  - Ovarian granulosa cell tumours (GCT) occur rarely and represent 2-3% of all
      ovarian tumours. Regarded as tumours with low malignant potential and renowned
      for late recurrences, these tumours occasionally metastasize to the liver. We
      present our experience with three patients who underwent secondary cytoreductive
      surgery including liver resection for recurrence of the disease resulting in
      greatly improved quality of life and disease-free interval.

PMID- 21077486
TI  - Ovarian carcinomatosis presenting as bilateral inguinal hernia: a brief report.
AB  - The differential diagnosis for what may seem an inguinal hernia may be complex,
      as lateral pain may be of many types of origin. We report the case of a 48-year
      old female patient who presented with a history of painful, progressively
      protruding soft bulging masses over the bilateral inguinal area and a 20-year
      history of head cancer and hepatitis B virus. Pathological analysis,
      gynecological ultrasound and abdominal computed tomography scan were required to
      make final determination. Final diagnosis was Stage IV ovarian carcinomatosis,
      which responded to chemotherapy. Initial diagnosis of inguinal hernia should not
      rule out other potential diagnoses, particularly in complex cases with other risk
      factors.

PMID- 21077487
TI  - Serous ovarian cystadenocarcinoma incidentally discovered in a 29-year-old
      patient: case report.
AB  - This is a review of a case of Stage I A serous ovarian cystadenocarcinoma in a 29
      year-old patient. The patient had no symptoms of illness. She underwent a
      surgical intervention because of cysts in both of her ovaries. By
      histopathological examination of the tissue sample taken during the surgical
      intervention, it was discovered that the patient suffered from a serous
      cystadenocarcinoma in her left ovary. Five years after the surgical intervention
      there have been no symptoms of relapse.

PMID- 21077488
TI  - Chemotherapy with low-dose bevacizumab and carboplatin in the treatment of a
      patient with recurrent cervical cancer.
AB  - Management of patients with recurrent or advanced cervical cancer is a challenge.
      Concurrent chemotherapy has become the mainstay of treatment and platinum remains
      the most effective single agent. Combinations of other agents have not
      demonstrated significant advantages. The application of angiogenesis inhibitors
      such as bevacizumab, an antibody inhibiting vascular endothelial growth factor,
      in metastatic or advanced cervical cancer remains to be evaluated. We present the
      case of a patient with platinum-resistant recurrent cervical cancer treated with
      low-dose bevacizumab and carboplatin, with resultant improved disease progression
      and tolerable toxicity profiles.

PMID- 21077489
TI  - Groin recurrence following stage IA squamous cell carcinoma of the vulva with
      negative nodes on superficial inguinal lymphadenectomy.
AB  - PURPOSE OF INVESTIGATION: Stage IA vulvar cancer with a depth of stromal invasion
      less than 1 mm is generally managed by wide local excision alone since there is
      less than 1% risk of lymph node involvement. CASE: A 62-year-old patient was
      admitted to a university hospital with a suspicious vulvar lesion. RESULTS: We
      present the first case of inguinal node and a possible contralateral pubic ramus
      recurrence following bilateral superficial inguinal lymphadenectomy and wide
      local resection for Stage 1A vulvar cancer. CONCLUSION: There is no evidence that
      extended radical surgery provides a better overall survival or reduces recurrence
      rate in Stage 1A vulvar carcinomas. Conservative vulvar resection and sentinel
      node dissection seem to be a rational choice. Nevertheless the disease may recur
      in the inguinal areas and frequently be lethal, therefore close surveillance and
      early attempts to treat the recurrent disease before infection and inflammation
      ensues should be the aim of current treatment strategies.

PMID- 21077490
TI  - A practical approach to the prevention of miscarriage: Part 3--Passive
      immunotherapy.
AB  - PURPOSE: To evaluate the efficacy of passive immunotherapy in preventing
      miscarriage. METHODS: Studies both pro and con concerning intravenous
      immunoglobulin therapy (IVIG) in preventing miscarriage were evaluated. A new
      therapy of i.v. intralipid infusion is also reviewed. RESULTS: Intravenous
      immunoglobulin therapy may be effective but it is necessary to use it prior to
      conception and monthly thereafter. Some brands are more potent than others. The
      data concerning intralipid i.v. infusion involves only small case series but the
      results from one study were encouraging though we could not personally
      substantiate these findings. CONCLUSIONS: Intravenous immunoglobulin therapy is
      very expensive. In the author's opinion there are no immunological studies that
      can determine if a woman needs immune suppression. The best way to decide is the
      history--the more miscarriages without any other identifiable cause the more
      likely passive immunotherapy may be helpful. If intralipid proves as efficacious
      as IVIG it will be a lot less expensive.

PMID- 21077491
TI  - Advantages of using a lower vs higher dosage of gonadotropins for follicular
      maturation including cycles of in vitro fertilization-embryo transfer.
AB  - PURPOSE: To demonstrate the benefits of using lower dosage FSH stimulation for
      follicular maturation in in vitro fertilization (IVF) cycles and in non-IVF
      cycles. METHODS: Several studies are evaluated in which either high or lower
      dosage gonadotropins were used in IVF and non-IVF cycles. The patient population
      were women either with diminished or normal ovarian egg reserve. RESULTS: Very
      poor pregnancy rates were found with high dosage gonadotropins when there was
      diminished egg reserve. In contrast pregnancy results per transfer were
      comparable to women with normal egg reserve when low dose gonadotropin regimens
      were used. CONCLUSIONS: Low dose gonadotropin regimens have the benefit of
      reducing costs and risks of ovarian hyperstimulation without reducing efficacy
      and in some cases actually increasing pregnancy rates.

PMID- 21077492
TI  - The slow levonorgestrel-releasing intrauterine system (LNG-IUS) 20 mcg/day: a
      literature review.
AB  - The aim of the study is to present the mechanisms of action, indications,
      complications, contraindications and the necessary tests before the insertion of
      a levonorgestrel-releasing intrauterine system (Mirena). After a literature
      search in Pubmed, a narrative review in the field is presented.

PMID- 21077493
TI  - A novel method to assess the effect of uterine senescence by comparing pregnancy
      outcome in younger donors vs older recipients who are sharing a common pool of
      oocytes.
AB  - PURPOSE: To evaluate uterine senescence by comparing pregnancy rates in older
      recipients vs their younger donors who were actually trying to conceive
      themselves. METHODS: A retrospective analysis comparing clinical and delivered
      pregnancy rates in all infertile donors < or = age 35 sharing their eggs with a
      recipient age > or = 40 over a 6-year time span. These parameters were also
      evaluated in the first frozen embryo transfer from these couples (if they had
      one). RESULTS: The clinical and delivered pregnancy rates were similar in younger
      donors vs older recipients following fresh embryo transfer. There was a non
      significant trend for lower implantation rates in the younger donors. No
      differences were found when comparing frozen embryo transfers. CONCLUSIONS: These
      data support conclusions that the uterus of women > or = 40 does not inhibit
      embryo implantation.

PMID- 21077494
TI  - Cryopreservation of blastocysts using a modification of a simplified freezing
      protocol with a one step removal of cryoprotectant successfully used previously
      to freeze 2 pronuclear or multi-cell embryos.
AB  - PURPOSE: To describe a modification of a simplified freezing protocol for the
      cryopreservation of blastocysts. METHODS: 1.5 M glycerol was substituted as a
      cryoprotectant instead of propanediol. RESULTS: There was a survival rate of
      59.1% (13/22) with three live deliveries in seven transfers (42.9% per transfer).
      The implantation rate was 28.6% (4/14). CONCLUSIONS: This is the first
      description of a new technique for freezing blastocysts. A larger series is
      needed to determine if the good pregnancy rates will continue.

PMID- 21077495
TI  - Serum retinol-binding protein-4 levels in polycystic ovary syndrome patients
      undergoing controlled ovarian hyperstimulation for in-vitro fertilization cycle.
AB  - AIMS: To determine serum retinol-binding rotein 4 (RBP-4) levels in polycystic
      ovary syndrome (PCOS) patients undergoing controlled ovarian hyperstimulation
      (COH) for an in vitro fertilization-embryo transfer (IVF-ET) cycle and the
      possible correlation to COH variables. PATIENTS AND METHODS: 11 consecutive PCOS
      patients undergoing our routine IVF flexible multidose gonadotropin-releasing
      hormone (GnRH)-antagonist protocol. Blood was drawn three times during the COH
      cycle: (1) day 1 or 2 of menstruation, and prior to gonadotropin administration
      (Day-S) (Day-S); (2) day of or prior to human chorionic gonadotropin (hCG)
      administration (Day-hCG); and (3) day of ovum pick-up (Day-OPU). Levels of
      estradiol and serum RBP-4 were compared among the three time points. Serum RBP-4
      was measured with a commercial immunoassay. RESULTS: Results showed significantly
      lower levels of serum RBP-4 on Day-OPU and Day-hCG than on Day-S. Though
      significant correlations were observed between serum RBP-4 and body mass index,
      fasting glucose or glucose to insulin ratio, no correlations were found between
      serum RBP-4 and IVF treatment variables or pregnancy rate. CONCLUSION: While
      serum RBP-4 decreases during COH for IVF, there is apparently no correlation of
      serum RBP-4 levels with IVF treatment variables or outcome.

PMID- 21077496
TI  - A comparison of pregnancy rates following fresh and frozen embryo transfer
      according to the use of leuprolide acetate vs ganirelix vs cetrorelix.
AB  - PURPOSE: To determine if controlled ovarian hyperstimulation (COH) regimens using
      the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate result in
      higher pregnancy and implantation rates than COH regimens using the GnRH
      antagonists cetrorelix or ganirelix following fresh and frozen embryo transfer.
      METHODS: Retrospective analysis was performed evaluating the pregnancy rates with
      the first fresh and first frozen embryo transfer cycles according to which
      protocol was used. A haphazard decision was made on which protocol to use. Women
      were required to be < 40 years of age and have had > or = 5 eggs retrieved.
      RESULTS: Significantly lower implantation rates were seen with ganirelix compared
      to leuprolide acetate or cetrorelix. CONCLUSIONS: These data should hopefully
      encourage interest in a prospective study to determine if conclusions about the
      inferiority of ganirelix are not merely fortuitous.

PMID- 21077497
TI  - The effect of endometriosis on pregnancy outcome following in vitro fertilization
      embryo transfer (IVF-ET) in women with decreased egg reserve.
AB  - PURPOSE: To determine the effect of the presence of endometriosis on the
      delivered pregnancy rate following in vitro fertilization-embryo transfer.
      METHODS: A retrospective cohort analysis of fresh or frozen embryo transfer in
      women with diminished egg reserve having IVF-ET and who also had had a
      laparoscopy. The data was analyzed as to whether endometriosis was present or
      not. RESULTS: The data demonstrated that women with diminished egg reserve can
      achieve pregnancies following IVF-ET. The presence of endometriosis did not have
      any negative effects on pregnancy rates. CONCLUSIONS: At least in women with
      diminished egg reserve the presence of endometriosis did not impair outcome
      following IVF-ET.

PMID- 21077498
TI  - Association of the change in serum estradiol (E2) levels from the day of to the
      day after human chorionic gonadotropin (hCG) injection and pregnancy outcome
      following in vitro fertilization-embryo transfer (IVF-ET) in less than average
      responders.
AB  - PURPOSE: To determine if the change in serum estradiol (E2) from the day of human
      chorionic gonadotropin (hCG) injection to the day after predicts pregnancy and
      implantation rates following in vitro fertilization-embryo transfer (IVF-ET) in
      less than average responders. METHODS: A retrospective cohort analysis was
      performed in women with less than average follicular response as defined by a
      peak serum E2 on the day of hCG of < 1500 pg/ml despite a maximum stimulation
      gonadotropin protocol. Pregnancy and implantation rates were compared in five
      groups based on standard deviation (SD) below or above the mean. RESULTS: No
      differences were found in outcome in any groups including those that were 1-2 SD
      below the mean or within 1 SD below the mean or up to 2 SD above the mean. The
      group that was 2 SD above the mean seemingly had higher pregnancy and
      implantation rates but there were insufficient numbers to allow statistical
      comparisons. There did not appear to be any confounding variables among these
      groups. CONCLUSIONS: A drop in serum E2 in a group of women that were less than
      average responders was not associated with a lower chance of conception following
      IVF-ET.

PMID- 21077499
TI  - Effects of tamoxifen on tissue nitrite/nitrate levels and plasma lipid
      peroxidation in female rats.
AB  - PURPOSE OF INVESTIGATION: The effects of tamoxifen on lipid peroxidation and
      oxidant-antioxidant balance in an animal model were studied. METHODS: Twelve
      female adult rats were divided into two groups and DMSO and tamoxifen dissolved
      in DMSO were administered. Tissues taken from the brain, liver and ovary of rats
      were dissected. MDA, nitrite, nitrate levels and plasma LDL oxidation in brain,
      ovary and liver tissues were measured and compared. RESULTS: Induced LDL MDA
      levels were significantly lower in the tamoxifen group (p = 0.009). MDA levels in
      the liver were significantly lower in the tamoxifen group whereas nitrite levels
      were found significantly higher (p < 0.05). Brain and ovarian tissues
      demonstrated no significant difference with respect to MDA, nitrite and nitrate
      levels. CONCLUSION: Tamoxifen has no negative effects on lipid peroxidation in an
      animal model.

PMID- 21077501
TI  - Emergency obstetric hysterectomy at two tertiary centers: a clinical analysis of
      11 years experience.
AB  - This was a retrospective clinical study of emergency hysterectomy performed
      between 1997 and 2007 at two tertiary hospitals to study incidence, indications
      and maternal mortality. We included all women who required emergency hysterectomy
      to control major postpartum hemorrhage after delivery, following a pregnancy of
      at least 24 weeks' gestation, regardless of the mode of delivery. There were 12
      emergency hysterectomies, with a frequency of 0.0726% among 16,521 deliveries.
      Indications included uterine atony (4 cases), uterine rupture (3 cases), uterine
      retroversion (2 cases), abnormal placentation (2 cases) and amniotic fluid
      embolization (1 case). The result was two maternal deaths. Although emergency
      obstetric hysterectomy is a life saving operation, it is associated with high
      maternal mortality.

PMID- 21077500
TI  - Successful treatment of a female with chronic pseudo-intestinal obstruction with
      sympathomimetic amines and thyroid hormone replacement.
AB  - PURPOSE: To determine if a defect in sympathomimetic amines, which is a common
      cause of various undiagnosed pain syndromes in women could be the cause of
      chronic pseudointestinal obstruction. Furthermore to determine if this life
      threatening illness may similarly respond to sympathomimetic amines as in other
      pain syndromes, e.g., pelvic pain and interstitial cystitis. METHOD: A 23-year
      old, five foot, female with chronic pseudointestinal obstruction, who lost 35
      pounds down to 75 pounds, was treated with 15 mg dextroamphetamine sulfate and 50
      microg of L-thyroxin (her TSH thyroid hormone level was markedly suppressed in
      the face of a slightly low free thyroxin level. RESULTS: Her abdominal pain
      lessened then completely disappeared within a few weeks. Within one year she
      gained 25 pounds. CONCLUSIONS: Chronic pseudointestinal obstruction is another
      way idiopathic orthostatic edema (a condition found predominantly in women) may
      manifest. Similar to other gastrointestinal pain syndromes and pain in other
      areas, e.g., pelvis, bladder, head and joints, treatment with sympathomimetic
      amines results in dramatic improvement.

PMID- 21077502
TI  - Comparision of reproductive outcome of the women with hypogonadotropic
      hypogonadism and tubal factor infertility.
AB  - OBJECTIVE: To evaluate the outcome of women with hypogonadotropic hypogonadism
      (HH) undergoing in-vitro fertilization (IVF). MATERIALS AND METHODS: Data from 13
      cycles often hypogonadotropic patients treated with in vitro fertilization from
      the period January 2006 to January 2008 were analyzed and compared with treatment
      results from 20 patients with tubal factor infertility (TI). All patients
      underwent ovarian hyperstimulation for IVF/ICSI at the same center. HH patients
      initiated the treatment by receiving daily injections of hMG. The patients in the
      control group were given the same dosage of recombinant FSH. RESULTS: Demographic
      characteristics of the patients were comparable. Mean duration of stimulation was
      13 days in the HH group and nine days in the TI group; the difference was
      significant (p < 0.001). Significantly more gonadotropins were used for the
      stimulation of HH patients (p < 0.05). Peak serum E2 concentration was found to
      be higher in the TI group. We evaluated the proportion of metaphase II (MII)
      oocytes to total oocytes retrieved in HH patients and found the number was
      similar to the TI group. Despite that fertilization and implantation rates were
      similar in both groups, the cancellation rate was higher in the HH group (23.1%
      vs 0). However pregnancy and live birth rates were similar. CONCLUSIONS: The
      present study showed that HH women undergoing IVF/ICSI are good responders. The
      treatment of HH women with IVF/ICSI did not increase multiple pregnancies and
      OHSS rates over the TI group.

PMID- 21077503
TI  - Effect of long-time administration of tibolone on vaginal cytology of castrated
      rats.
AB  - PURPOSE: To evaluate the estrogenic effect of tibolone administered at high-dose
      and long-term through cytological examination of vaginal epithelium of castrated
      rats. METHODS: 15 adult Wistar rats were submitted to bilateral oophorectomy 30
      days before starting the experiment. The rats were then randomly divided in two
      groups. Experimental rats (n = 9) orally received 1 mg tibolone/day; control rats
      (n = 6) just received carboxymethylcellulose. Vaginal smears were collected from
      all rats on days 0, 1-6, 30, 60, 90 and 120 of the experiment. RESULTS: On day 0,
      smears from all rats were atrophic, classified as anestrus, and remained this
      type in the control group until day 120. In the tibolone group, on day 3 all the
      rats had vaginal cytology similar to estrus and maintained the same aspect till
      day 90. CONCLUSION: Tibolone has estrogenic action in the vaginal epithelium
      which is already evident after the first dose and remains without major changes
      over time.

PMID- 21077504
TI  - Vaginal fluid pH, cervicovaginitis and cervical length in pregnancy.
AB  - AIM: The purpose of this prospective study was to determine the possible
      association among vaginal fluid pH, cervicovaginitis and cervical length in
      singleton pregnancies at 16-22 weeks of gestation. METHODS: A total of 240
      asymptomatic singleton pregnancies at 16-22 weeks of gestation were included to
      the study. Vaginal fluid pH was determined using pH paper in a sterile speculum
      examination, and cervical length was examined by transvaginal ultrasonographic
      measurement. Vaginitis was diagnosed by pH determination and wet mount smear;
      cervicitis was diagnosed by cervical examination. Patients were followed to
      delivery and hospital records were reviewed to extract obstetric information.
      Preterm delivery was defined as delivery at or prior to 36 weeks of gestation.
      Abnormal pH was defined as a pH of > 5.0. Patients with cervicovaginitis (n = 72)
      were compared with those without any trace of infection (n = 60). RESULTS: The
      mean gestational age was 20.3 +/- 1.4. We found an significant association among
      cervicovaginitis, cervical length and vaginal pH. There was a significant
      correlation between an elevated vaginal pH (> 5.0) and a shortened cervical
      length (r = -0.59, p < 0.001). Vaginal fluid pH > 5.0 was associated with
      increased risk of preterm delivery (OR 4.3, 95% CI 2.0, 9.3; p = 0.001) as well
      as delivering an infant of less than 2,500 g (OR 4.0, 95% CI 1.4, 11.0; p =
      0.009). CONCLUSIONS: Elevated vaginal fluid pH in women at 16-22 weeks of
      gestation seems to be associated with a decreased cervical length and increased
      risk of preterm delivery.

PMID- 21077505
TI  - Perineal ultrasound evaluation of urethral mobility after the TVT-O procedure.
AB  - AIMS: The aim of study was to assess, by means of perineal ultrasound (US), women
      treated with the trans-obturator suburethral sling procedure for urinary stress
      incontinence (USI). METHODS: Twelve women with USI and urethral hypermobility
      were enrolled. Static and dynamic perineal US of urethral mobility was performed
      before and after tension-free vaginal tape opturator (TVT-O) procedure: US
      parameters evaluated were pubis-urethra distance and inclination angle of the
      urethral axis. RESULTS: The Valsalva stress US evaluation showed a return to
      normal range of the pubic urethral distance in all cases (p = 0.0001); also a
      correction of the angle of inclination of the urethral axis occurred in all
      patients (p < 0.0001). CONCLUSIONS: Our results propose the use of perineal US
      for patients with USI as an additional diagnostic tool and a means for
      postsurgical follow-up.

PMID- 21077506
TI  - Is placebo as effective as estrogen regimens on vasomotor symptoms in women with
      surgical menopause?
AB  - OBJECTIVE: To evaluate the short-term effects of two hormone therapy (HT)
      regimens and placebo on the Greene Climacteric Scale (GCS) of women with surgical
      menopause following six months of treatment. METHODS: This 6-month, prospective,
      randomized, parallel-group, masked evaluator study compared the efficacy of once
      daily administration of 0.625 mg conjugated equine estrogen (group I), 3.9 mg
      transdermal 17beta-estradiol patch applied every week (group II) and placebo
      (group III). Mean GCS before and after six months of treatment in each group was
      compared. RESULTS: In groups I and II, vasomotor symptoms (p < 0.005, p < 0.05),
      somatic symptoms (p < 0.05, p < 0.05) and total score (p < 0.005, p < 0.01)
      significantly reduced from baseline values respectively, while the other
      subscores revealed no statistically important differences following six months of
      HT. In group III, vasomotor (p < 0.05), subscore and total score (p < 0.05)
      decreased significantly while other subscore reductions were not significant.
      CONCLUSIONS: Estrogen regimens and placebo seem to be effective in alleviating
      vasomotor symptoms. Additional larger prospective randomized studies need to be
      conducted in an aim to look at not only short-term but also long-term effects on
      climacteric symptoms, in comparison to both placebo arms and different dose and
      mode of HT use.

PMID- 21077507
TI  - Tubal ectopic pregnancy in the north of Jordan: presentation and management.
AB  - OBJECTIVE: To evaluate and compare the current approach to the management of
      ectopic pregnancy between the main two civil hospitals in the north of Jordan.
      DESIGN: A retrospective study. MATERIAL AND METHODS: A retrospective review was
      made of the records of all patients with confirmed ectopic pregnancy admitted to
      Princess Badea Teaching Hospital (PBTH), and King Abdullah University Hospital
      (KAUH) between January 1, 2005 and December 31, 2005. The total number of
      deliveries for the same period was obtained from the labor ward records of
      hospitals. Information regarding demographic data, presenting symptoms, methods
      of diagnosis and treatment were extracted from individual patient records.
      RESULTS: There were 50 cases of confirmed ectopic pregnancy in PBTH compared with
      20 cases in KAUH. The total number of deliveries at PBTH was 9,000 (1 ectopic/180
      deliveries) while at KAUH, the number of deliveries was 3,000 so the ratio was 1:
      150. The majority of patients (82%) had ruptured ectopic pregnancy at
      presentation. All cases at PBTH were managed by laparotomy. Of the 20 cases at
      KAUH, five cases were managed laparoscopically and three received medical
      treatment for their ectopics. There was no maternal mortality from ectopic
      pregnancy or its management at either hospital. CONCLUSION: The management of
      ectopic pregnancy in our community is still suboptimal. We recommend the
      development of clinical protocols for early diagnosis and referral, training in
      transvaginal scanning and an increase in the use of laparoscopy for the
      management of ectopic pregnancy.

PMID- 21077508
TI  - Umbilical cord prolapse in the southeast region of Turkey: evaluation of 79
      cases.
AB  - OBJECTIVE: The aim of the study was to determine the risk factors and perinatal
      outcomes of umbilical cord prolapse (UCP). MATERIAL AND METHODS: This study was
      performed at Dicle University between January 2000 and December 2008 on 79 cases
      in which deliveries were complicated by umbilical cord prolapse. RESULTS: 0.36%
      of all deliveries were complicated by umbilical cord prolapse. The presentation
      of the fetuses were as follows: vertex, breech and transverse lie and foot
      presentation. Thirty-four (43%) fetuses with UCP had a fetal weight of < or =
      2500 g as compared with nine (9%) for fetuses in the control group (p < 0.05).
      Mothers in the study group were 1.3 times more likely to be multiparas than the
      control group (p = 0.16) Cesarean section was performed in 76 cases (96.2%) and
      there were nine (11.3%) perinatal deaths. CONCLUSION: Umbilical cord prolapse is
      a risk factor of perinatal morbidity and mortality. Fetal weight < or = 2500 and
      abnormal fetal presentation are associated with increased risk of umbilical cord
      prolapse. Cesarean section resulted in a significantly decreased risk of
      perinatal mortality.

PMID- 21077509
TI  - Adolescent pregnancies and obstetric outcomes in southeast Turkey: data from two
      regional centers.
AB  - PURPOSE OF INVESTIGATION: To evaluate adolescent pregnancy and obstetric
      outcomes. METHODS: This retrospective cohort study was performed by analysis of
      patient files and birth records of pregnant women who delivered in two cities in
      Southeast Anatolia, Turkey. Pregnant women aged 19 years old and younger were
      included in the study group. Women between 20 and 35 years of age constituted the
      control group. RESULTS: The incidence of adolescent pregnancy during the study
      period was 11%. Birth weight and hemoglobin level were significantly higher in
      the control group (p < 0.05). The majority of the women in the study group
      delivered vaginally (p < 0.05). The incidence of preterm labor, intrauterine
      growth retardation, and stillbirth was significantly higher in the study group (p
      < 0.05). Adolescent mothers were most likely to have low birth weight and very
      low birth weight babies (p < 0.05). CONCLUSION: Adolescent pregnancies were
      associated with adverse pregnancy outcomes in our study population. Possible
      grounds for such increase warrant further evaluation and discussion.

PMID- 21077510
TI  - Pregnancy-related acute renal failure in the southeast region of Turkey: analysis
      of 75 cases.
AB  - OBJECTIVE: To study the clinical profile, management and outcome of the patients
      with pregnancy-related acute renal failure (PRARF). METHODS: All patients with
      PRARF admitted between January 2006 and January 2009 were analyzed. RESULTS: The
      total number of women with PRARF was 75. Age range of women with PRARF was 21 to
      46 years and 36% of the cases of PRARF were seen in the postpartum period. PRARF
      was caused by sepsis in 14.6%, toxemias of pregnancy in 75.2%, and hemorrhage of
      pregnancy in 12%. Postabortal sepsis was the cause in 14.6%. Dialysis was needed
      in 33.3%. Maternal mortality rate was 10.6%. CONCLUSIONS: Pregnancy-related acute
      renal failure is a major health problem and carries very high mortality and
      morbidity. Poor healthcare facilities and lack of antenatal healthcare clinics
      are major identified causes.

PMID- 21077511
TI  - An analysis of hysteroscopy experience over a seven-year period.
AB  - PURPOSE OF INVESTIGATION: Over the years, hysteroscopy has been increasingly
      performed for various gynecological disorders. In this study, we present a review
      of hysteroscopic procedures performed over a 7-year period. METHODS: Five hundred
      and eighty hysteroscopic procedures performed at the Department of Gynecology and
      Obstetrics, University of Gaziantep, Turkey from 2002 to 2009 were reviewed
      particularly highlighting the preoperative indications, postoperative diagnoses
      and complications associated with the procedure retrospectively. RESULTS: The
      most common indication for diagnostic hysteroscopy was infertility followed by
      AUB. The most common pathologies for referal to operative hysteroscopy were
      uterine septum, endometrial polyps, Asherman's syndrome, submucous myomas, and
      other uterine anomalies. The complication rate was 0.86% of the total
      hysteroscopies. False passage and uterine perforation were the most common acute
      complications. No late complications occurred. CONCLUSION: Our data is consistent
      with reports from other studies supporting that hysteroscopy is a safe and
      effective minimally invasive procedure with a low rate of complications with
      certain surgical principles.

PMID- 21077512
TI  - Is insulin-dependent diabetes and obesity a predisposition for endometrial and
      pancreatic carcinoma?
AB  - Among 178 patients operated for endometrial carcinoma during a five-year period,
      17 were re-operated at the Institute of Surgery (9.5%) because of pancreatic head
      carcinoma. The frequency of insulin-dependent diabetes was pointed out in
      patients-- 28% of those who were first diagnosed with endometrial carcinoma.
      Moreover in the same group diagnosed with endometrial carcinoma, we found 17 to
      have pancreatic carcinoma, and among those there were 12 cases that had diabetes
      (70.58%).

PMID- 21077513
TI  - Peripartum cardiomyopathy and Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder of unknown
      etiology characterized by venous malformations or varicose veins, cutaneous
      capillary malformation and hypertrophy of soft tissues with limb (usually
      asymmetric lower extremity) involvement. Peripartum cardiomyopathy (PPCM) is
      characterized by rapid onset heart failure during the final month of pregnancy or
      within five months of delivery, in the absence of identifiable risk factors or
      previous heart disease. The aim of this study was to illustrate the correlation
      between the KTS and the onset of PPCM in women with twin pregnancies. Our case is
      a 35-year-old woman, gravida II para I, with KTS, twin pregnancy and PPCM. We can
      assume that, as the heart of a women with KTS usually works with a low preload
      reserve due to the widespread venous varicosities, if a significant increase in
      preload occurs, it may lead to the onset of cardiac dilatation and thus PPCM.

PMID- 21077515
TI  - Antisperm antibodies and human reproduction.
AB  - PURPOSE: To present strategies in diagnosing and treating infertility related to
      antisperm antibodies. METHODS: Antisperm antibodies (ASA) were detected on sperm
      using the direct immunobead (IBD) test. Treatments included intrauterine
      insemination (IUI) with pretreatment with chymotrypsin/galactose vs. in vitro
      fertilization (IVF) with intracytoplasmic sperm injection (ICSI). RESULTS:
      Intrauterine insemination with protein digestive enzyme treatment was much more
      effective than IUI without enzymatic therapy. However IVF with ICSI provided
      three times the pregnancy rate for males with sperm coated with ASA than IUI with
      chymotrypsin treated sperm. CONCLUSIONS: It is advisable to include measurement
      for ASA on the initial semen analysis. However, another option is to perform it
      initially only with an abnormal post-coital test. The decision for IUI with
      chymotrypsin pretreatment of the sperm vs. IVF with ICSI may depend on insurance
      and financial issues.

PMID- 21077514
TI  - Novel therapeutic strategy for uterine arteriovenous fistulas: case report.
AB  - BACKGROUND: The major presenting symptom of uterine arteriovenous fistulas is
      massive, torrential vaginal bleeding, the degree of which often leads to a shock
      state. CASE: A 35-year-old woman, gravida 3, para 2 presented with massive
      vaginal hemorrhage at the first menstruation six months after delivery. Uterine
      arteriovenous fistulas were diagnosed by color Doppler ultrasonography (US),
      dynamic computer tomography (CT), and conventional angiography. The patient
      underwent hysterectomy after bloodstream decrease by bilateral uterine artery
      embolization. CONCLUSION: The extent of uterine arteriovenous fistulas was
      diagnosed by color Doppler US, CT, and pelvic angiography, and this precise
      evaluation led to an adequate therapeutic strategy for uterine arteriovenous
      fistulas.

PMID- 21077516
TI  - Recurrent aneuploidy--fact or fiction.
AB  - PURPOSE: To evaluate the likelihood that some women are more prone to forming
      chromosomally abnormal embryos unrelated to age. METHODS: The literature
      involving studies suggesting that predisposition to aneuploidy does exist was
      reviewed. In addition a new anecdotal unpublished report on a tendency to form
      trisomies is presented and a couple of case reports dealing with the possibility
      of predisposition to polyploidy are discussed. RESULTS: The results of in vitro
      fertilization and pre-implantation diagnoses confirm the suspicion that some
      women are more prone to trisomies or polyploidy. CONCLUSIONS: In vitro
      fertilization with pre-implantation genetic diagnosis may help in preventing
      miscarriage from recurrent polyploidy but is not so valuable for recurrent
      trisomies.

PMID- 21077517
TI  - Evidence that high serum progesterone (P) levels on day of human chorionic
      gonadotropin (hCG) injection have no adverse effect on the embryo itself as
      determined by pregnancy outcome following embryo transfer using donated eggs.
AB  - PURPOSE: To determine if too high of a level of progesterone at the time of peak
      follicular maturation of donors adversely affects pregnancy or implantation rates
      of recipients. METHODS: A retrospective cohort analysis was performed on donor
      egg recipients. Pregnancy rates were calculated according to ranges of five serum
      progesterone (P) levels based on two standard deviations before and above the
      mean. RESULTS: No adverse effect was found in recipients whose donors had serum P
      levels between 2.47 and 3.41 ng/ml. There may have been a slightly lower
      pregnancy rate in recipients whose donors had seen P levels over 3.41 but there
      were only seven patients in that group and there still was a live delivered
      pregnancy rate of 28.6% per transfer. CONCLUSIONS: The main adverse effect of a
      premature rise of progesterone in women making multiple follicles with
      gonadotropin stimulation seems to be on the endometrium. There appear to be
      enough follicles not affected by the progesterone to recommend proceeding with
      oocyte retrieval in the donor so as not to waste money on expensive medication
      and monitoring.

PMID- 21077518
TI  - Effect of the length of time that donated embryos are frozen on pregnancy
      outcome.
AB  - PURPOSE: To determine if the longer length of time that embryos donated to an
      anonymous couple have been frozen has a negative effect of subsequent successful
      pregnancy following thawing and transfer to the recipients. METHODS:
      Retrospective determination of pregnancy rates according to the length of
      cryopreservation time has on pregnancy outcome following transfer of embryos
      designated for donation. RESULTS: Longer time of freezing did not adversely
      affect subsequent pregnancy rates following frozen embryo transfer. CONCLUSIONS:
      Donated embryos frozen for over five years (the time when some countries demand
      that the embryos be discarded) contributed to one-fourth of the donor embryo pool
      and one-third of the live deliveries.

PMID- 21077519
TI  - Effect of fertilization by intracytoplasmic sperm injection versus conventional
      insemination on embryo cleavage rates.
AB  - PURPOSE: To determine if fertilization by conventional oocyte insemination vs
      intracytoplasmic sperm injection (ICSI) causes any difference in the maximum
      number of blastomeres of fresh or frozen thawed embryos transferred. METHODS:
      Retrospective evaluation of all in vitro fertilization (IVF) cycles over a 10
      year period in cycles having a 2 embryos transferred where the semen analysis was
      normal except for strict morphology which was allowed to be 2-5% normal. The
      percentage of the maximum number of blastomeres in any transfers was compared
      according to the method of insemination. RESULTS: There were no differences in
      the maximum blastomere numbers in cycles where there was conventional
      insemination vs ICSI. CONCLUSIONS: Though higher pregnancy rates have been found
      following the transfer of embryos derived from conventional oocyte insemination
      vs ICSI, and higher pregnancy rates were found following single embryo day 3
      transfers with embryos with more blastomeres, the beneficial effect of
      conventional insemination does not seem to be related to forming embryos with
      more rapid cleavage.

PMID- 21077520
TI  - Length of time of embryo storage does not negatively influence pregnancy rates
      after thawing and transfer.
AB  - PURPOSE: To determine if longer storage of embryos in a cryopreserved state
      negatively affects the chance of successful implantation following thawing and
      transfer. METHODS: A retrospective cohort analysis of frozen-thawed embryos that
      had been donated to recipients. Four time periods were evaluated. RESULTS: No
      significant decrease in pregnancy or implantation rates was found in the longest
      freezing group (> or =6 years). In fact, if there was a trend, it was for
      improved pregnancy rates with longer storage. One of the successes was from
      embryos stored about 12 years. CONCLUSIONS: Hopefully these data and results from
      other IVF centers will influence those countries having a mandatory discarding
      policy to reconsider and lift these restrictions, especially to increase the pool
      of embryos available for donation.

PMID- 21077521
TI  - Pretreatment of sperm with low hypo-osmotic swelling tests with chymotrypsin
      prior to intrauterine insemination (IUI) and avoidance of unprotectected
      intercourse results in pregnancy rates comparable to IUI for other male factor
      problems.
AB  - PURPOSE: To carry out a retrospectively performed matched controlled study to
      determine the efficacy of pretreatment of sperm having low hypo-osmotic swelling
      (HOS) test scores with chymotrypsin galactose prior to intrauterine insemination
      (IUI) compared to IUI for other types of male factor problems. The women with
      male partners with low HOS scores were advised not to have unprotected
      intercourse. METHODS: All cycles having IUI with chymotrypsin treated sperm for
      low HOS scores were matched with the very next woman having IUI for sperm with
      other male factor problems but with normal HOS scores. RESULTS: There was a
      significantly higher clinical pregnancy rate with chymotrypsin treated sperm
      (32.3% per IUI) vs. 21.9% for other male factor cases. The live birth rate per
      IUI cycle was not significantly different (21.2% vs. 15.4%). CONCLUSIONS: These
      results now show that pretreatment of sperm with low HOS scores allows very good
      pregnancy rates following IUI as long as the couple is cautioned about
      unprotected intercourse. These data support the concept that sperm with low HOS
      test scores impair fertility by transferring a toxic factor from the sperm to the
      zona pellucida to the embryo membrane which impairs the embryos from implanting.

PMID- 21077522
TI  - Evaluation of the feasibility of a new method for performing chorion villus
      sampling.
AB  - OBJECTIVE: This study aimed to evaluate the usefulness and safety of a new method
      for taking a placental biopsy. METHODS: The procedures were performed using the
      traditional single needle technique (group 1) or the new method (group 2). In
      group 2, the piston was fixed in a simple metallic clip and the negative pressure
      was maintained in a continuous manner which was controlled with a three-way
      stopcock. RESULTS: Multiple uterine insertion was necessary in 14 cases (32.6%)
      in group 1 and five (11.9%) in group 2 (p < 0.05). The amount of chorionic tissue
      obtained was significantly higher in group 2 (19.1 +/- 15.0 mg vs. 33.9 +/- 17.4
      mg p < 0.05). The abortion rates did not differ in either group. CONCLUSION:
      While using this technique, the operator is capable of performing the procedure
      without any assistance and of applying constant negative pressure only in the
      placenta. The advantageous outcomes are probably related to the size as well as
      the incessant fashion of the vacuum force.

PMID- 21077523
TI  - Expression of matrix metalloproteinase-9 (MMP-9) in human midpregnancy amniotic
      fluid and risk of preterm labor.
AB  - OBJECT: This work stands as a pilot study in assessing the reliability of
      metalloproteinase-9 (MMP-9) as a marker for intraamiotic infection and preterm
      birth already in early pregnancy. SUBJECT: 100 amniotic fluids taken at the
      Midwife Obstetrics and Gynaecological Clinic of the University of L'Aquila
      (Italy). RESULTS: Our results show that MMP-9 is a sensitive marker of
      intraamionic infection (an important risk factor for preterm delivery) already in
      early pregnancy, because only women with a significant elevation were
      subsequently exposed to preterm birth. CONCLUSIONS: Early identification of women
      at risk of preterm birth is of important clinical significance. Indeed exposing
      women to deep diagnostic and therapeutic protocols could possibly reduce the
      incidence of preterm birth in the near future and have a positive impact on fetal
      prognosis related to unknown intraamniotic infection.

PMID- 21077524
TI  - Diabetes supersedes dobutamine stress echocardiography in predicting cardiac
      events in female patients.
AB  - BACKGROUND: The many available choices for testing for coronary artery disease
      (CAD) brought about several questions regarding suitability of certain tests for
      different groups of patients and the prognostic value of obtained results in
      predicting events and mortality. The aim of this study is to describe the
      prognostic value of dobutamine stress echocardiography (DSE) results in
      predicting cardiac events and mortality in > or = 60-year-old females. METHODS:
      49 women (> or = 60 years old) who were referred for DSE were included in the
      study. Data including CAD risk factors, and results of tests and a follow-up of
      events (MI, unstable angina, progression of CHF) and death. RESULTS: Eleven
      patients were considered to have a positive DSE result. There was no difference
      between DSE (+) and DSE (-) patients in cardiac events and cardiac death. However
      when interventions were included to events, analysis showed DSE (+) to have more
      overall events. Non-cardiac deaths and "all deaths" were 11 and 8 times more
      common among DSE (+) patients compared with DSE (-) patients p < 0.01.
      Multivariable logistic regression showed that diabetics and DSE (+) patients were
      32 (p = 0.01) and 23 (p = 0.02) times more likely to have an event compared with
      non-diabetics and DSE (-) patients, respectively. CONCLUSION: DSE is a safe
      procedure to be used in > or = 60-year-old female patients and can provide
      informative prognostic information regarding all-cause deaths and cardiac events
      (including interventions) over a 4-year period. In addition we find that diabetes
      is a strong predictor of events regardless of DSE result.

PMID- 21077525
TI  - What kind of care and support do infertile women undergoing fertility treatment
      in Greece expect? A questionnaire survey.
AB  - The aim of this study was to identify infertile women's expectations and
      perceived importance of professional psychosocial services and to identify the
      predictors of their expectations. The study included 404 infertile women. Most
      women sought more medical information and more emotional support than what was
      offered, mainly by the hospital staff. Less than half the women rated
      psychosocial services as important. The main predictors of the importance of
      ratings were high fertility-related stress, low provision of social support, low
      social class and male infertility factor. A provision for information regarding
      the medical and psychosocial aspects of infertility should be included in routine
      care in fertility clinics. Although it seems possible to meet the emotional and
      psychosocial needs of less distressed women through information and support, it
      is necessary to offer professional psychosocial services to more distressed
      women.

PMID- 21077526
TI  - Comparison of bolus remifentanil-propofol versus bolus fentanyl-propofol for
      dilatation and sharp curettage.
AB  - BACKGROUND AND OBJECTIVE: The study was conducted to determine whether bolus
      administrations of remifentanil-propofol could provide adequate analgesia and
      similar patient comfort with a faster recovery profile compared with bolus
      administrations of fentanyl-propofol during dilatation and sharp curettage.
      METHODS: The patients were randomized to a remifentanil group (n=36) or fentanyl
      group (n=36). The remifentanil group received an IV bolus dose of 1 pg kg(-1)
      remifentanil. The fentanyl group received an IV bolus dose of fentanyl 0.5 microg
      kg(-1). The Verbal Pain Scale (VPS), modified Aldrete scores, blood pressure,
      heart rate, peripheric oxygen saturation, recovery time from anesthesia and
      adverse events during or after surgery were evaluated. RESULTS: The groups were
      found to be similar in duration of the surgical procedure, anesthesia time and
      hemodynamic variables and VPS scores. Patients in the remifentanil group
      recovered from anesthesia earlier. Modified Aldrete scores were higher in the
      remifentanil group at 5 and 10 min postoperatively. The frequency of
      perioperative adverse events did not differ significantly between the groups.
      CONCLUSIONS: Bolus injections of remifentanil appear to be a safe and effective
      alternative to fentanyl, producing faster recovery in providing analgesia during
      dilatation and sharp curettage procedures.

PMID- 21077527
TI  - Factors affecting maternal and perinatal outcomes in HELLP syndrome: evaluation
      of 126 cases.
AB  - OBJECTIVES: To ascertain the characteristics, clinical features, and maternal
      fetal outcome in HELLP (hemolysis elevated liver enzymes, low platelets) syndrome
      at a tertiary referral center. MATERIAL AND METHODS: This was a cross-sectional
      study carried out at Dicle University between January 2004 and December 2008 in
      which the charts of 126 cases were retrieved retrospectively and data analyzed
      descriptively. RESULTS: Of all deliveries 0.9% were complicated by HELLP
      syndrome. Of the cases with HELLP syndrome 79 (62.6%) had preeclampsia, 28
      (22.2%) had eclampsia and 19 (15.2%) had a diagnosis of HELLP syndrome. The
      values of significant biochemical parameters (mean +/- SD) were documented as ALT
      (alanin aminotransferase) 224 +/- 42 IU/I and ALT1 (after birth) 140 +/- 22, AST
      379 +/- 23 IU/l and AST1 215 +/- 51, LDH (lactate dehydrogenase) 1418 +/- 67 IU/l
      and LDH1 875 +/- 16, together with the hematological parameters as platelet count
      (86 +/- 12 K/Ul), urine protein (3 + in urine test stick) and albumin levels (2 +
      0.9 g/dl). Eighty-six (68.25%) of the patients required albumin replacement.
      Thirty-one (24.6%) cases were nullipara and 95 (75.4%) multipara; of which 32
      women (25.4%) were in Class I, and 94 (74.6 %) in Class II of complete HELLP
      syndrome. Regular antenatal examination was accomplished in a very small number
      of patients (12.25%). Fifty-eight (46.03%) patients required transfusions with
      blood or blood products and 12 (9.5%) underwent laparotomy due to major
      intraabdominal bleeding. Magnesium sulphate to prevent convulsions and
      corticosteroids (12 mg betametazone) to enhance fetal lung maturity were
      administered. Forty-four (34.9%) cases had vaginal delivery and 82 (65.1%)
      cesarean section; another 18 (14.2%) were with in utero stillbirth. Fifteen
      babies (11.9%) died, 26 (20.63%) developed placental abruption, 14 (11.11%) acute
      renal insufficiency, and 13 (10.31%) postoperative subcutaneous hematomas.
      Maternal mortality occurred in ten cases (7.93%). CONCLUSION: HELLP syndrome is a
      pathology associated with a high incidence of maternal and perinatal
      complications. Laboratory parameters in cases with HELLP syndrome are not
      efficient in detecting perinatal results, but can be used as risk denominators in
      evaluating maternal complications. Therefore, for patients with HELLP syndrome,
      standard antenatal follow-up protocols should be applied in order to obtain early
      diagnosis and improve the speed of transfer to obstetric departments with
      expertise in this field.

PMID- 21077528
TI  - Evaluation of serum levels of interleukin-10, interleukin-11 and leukemia
      inhibitory factor in differentiation of eutopic and tubal ectopic pregnancies.
AB  - PURPOSE OF STUDY: To investigate whether serum levels of leukemia inhibitory
      factor (LIF), interleukin 10 (IL-10) and interleukin 11 (IL-11) are different in
      reference to the site of implantation. METHODS: Seventeen patients with
      laparoscopic diagnoses of tubal ectopic pregnancy (EP) and 19 patients with
      intrauterine pregnancy delivering healthy term neonates (IUP) were prospectively
      evaluated for LIF, IL-10 and IL-11 levels. The data were compared by using the
      Student's t-test, chi-square test, Kruskal-Wallis and the Mann-Whitney U test
      with Bonferroni's correction (p < 0.05) as appropriate. RESULTS: A statistically
      significant difference was observed in serum LIF levels between the EP and IUP
      groups (p = 0.002). Ranges of LIF were 15-300 and 70-1200 ng/ml for the IUP and
      EP groups, respectively. There were no significant differences between groups in
      terms of IL-10 and IL-11 levels. CONCLUSION: LIF, but not IL-10 or IL-11, levels
      may be increased in early tubal ectopic pregnancies when compared to normal
      intrauterine pregnancies.

PMID- 21077529
TI  - Analysis of uterine rupture cases in Agri: a five-year experience.
AB  - INTRODUCTION: We attempted to establish the frequency of uterine rupture and to
      address etiological factors, complications, management and maternal and perinatal
      outcome of complete versus incomplete rupture, with the aim of proposing
      preventive measures. METHODS: The clinical records of uterine rupture cases
      managed at the Obstetrics and Gynecology Department of Agri Maternity and
      Children's Hospital in Turkey from June 2004 to June 2009 were analyzed
      retrospectively. RESULTS: There were 44 cases of ruptured uterus. Among 24,554
      deliveries the total incidence of uterine rupture was 1/558 or 17%. The most
      common site for the location of rupture was the fundal region (36.36%) followed
      by the lower segment, isthmic and mixewd types, respectively. DISCUSSION:
      Prevention must necessarily include regular antenatal care and meticulous
      screening of high-risk patients. Improved organization and access to maternal
      care, decentralization of obstetric services into peripheral care units in
      villages to prevent home deliveries and good supervision during labor can reduce
      the incidence of this preventable obstetric catastrophe.

PMID- 21077530
TI  - Pregnancy and adnexal torsion: analysis of 20 cases.
AB  - OBJECTIVE: To study the clinical profile, management and outcome of pregnancy
      complicated by adnexal torsion. METHODS: All pregnancy cases complicated by
      adnexal torsion admitted between January 2001 and January 2009 were analyzed.
      RESULTS: The total number of pregnant cases was 20. Age range of pregnant women
      with adnexal torsion was 18 to 42 years. Of these cases 70% were seen in the
      first and second trimester. Seventy percent of cases were operated by the
      laparotomy route and 30% by laparoscopy. Salpingo-oophorectomy was performed in
      70% of cases and detorsion in 30% of cases. Histopathologic examinations revealed
      five patients (25%) had serous cystadenoma, four patients (20%) mucinous
      cystadenoma, six patients (20%) dermoid cyst and five patients (25%) hemorrhagic
      cyst. CONCLUSIONS: Adnexal torsion as a differential diagnosis of acute abdomen
      in pregnancy should be considered and we recommend early surgical treatment that
      will save the adnexa.

PMID- 21077531
TI  - Intrauterine fetal demise due to streptococcal toxic shock syndrome: a case
      report.
AB  - BACKGROUND: Toxic shock syndrome caused by group A streptococci (GAS) is rare
      around the time of delivery, but it may predispose pregnant women to a life
      threatening condition. CASE: A 32-year-old primigravida at 21 weeks of gestation
      was taken to our hospital with acute severe abdominal pain following fever. On
      admission the fetus was found to be dead, and intrauterine fetal demise due to
      placental abruption was suspected. An emergency cesarean section found no sign of
      placental abruption. Soon after the surgery, the patient went into shock but was
      successfully treated with intensive care. Although repeated blood cultures failed
      to detect microorganisms, the patient was positive for streptococcal pyrogenic
      toxin A, which is a superantigen of GAS. CONCLUSION: Once GAS infection is
      suspected, regardless of negative blood cultures, supportive care in the
      intensive care unit is mandatory.

PMID- 21077532
TI  - A novel highly effective therapy for severe vasomotor symptoms in an estrogen
      deficient woman--case report.
AB  - PURPOSE: To describe a novel highly effective therapy for vasomotor symptoms
      associated with diminished oocyte reserve. METHODS: A 58-year-old estrogen
      deficient woman with severe vasomotor symptoms was treated with 20 mg per day of
      dextroamphetamine sulfate. RESULTS: A marked immediate improvement was noted.
      CONCLUSIONS: An acquired disorder of the sympathetic nervous system may be the
      etiologic factor for vasomotor symptoms in women with diminished egg reserve and
      treatment with sympathomimetic amines seems highly effective. This case will
      hopefully stimulate a larger series to determine its efficacy in a larger
      population.

PMID- 21077533
TI  - Anencephalic conjoined twins with mirror-image cleft lip and palate.
AB  - This is a case presentation of a conjoined twin (cephalothoracopagus) pregnancy
      with anencaphaly and mirror-image cleft lip and palate, affecting the left side
      of one twin and the right side of the other twin. The pregnancy was terminated at
      26 weeks. The case is discussed with information in the literature.

PMID- 21077534
TI  - Ovarian torsion; early diagnosis by MRI to prevent irreversible damage.
AB  - BACKGROUND: Early diagnosis of ovarian torsion can help prevent irreversible
      damage to the adnexal structures in women desiring to maintain fertility. CASE:
      The patient was transferred by ambulance for a six-hour history of severe lower
      abdominal pain. Magnetic resonance imaging (MRI) revealed bilateral enlarged
      ovaries measuring 5 x 6 cm (right) and 4 x 5 cm (left) with a right twisted and
      thickened peduncle. Ultrasonography failed to detect the peduncle changes. At
      surgery, the right adnexa was twisted 180 degrees in a clockwise direction with
      no findings suggestive of gangrenous change, hemorrhagic infarction or ischemic
      change. Detorsion of the twisted ovary was performed. CONCLUSION: Detection of
      tube torsion at MRI may be useful in the preoperative evaluation for surgical
      detorsion of twisted adnexa encountered in enlarged ovaries.

PMID- 21077535
TI  - Idiopathic edema, a condition associated with pelvic pain and other symptoms in
      women, as a remedial cause of chronic cold induced urticaria.
AB  - PURPOSE: To determine if the treatment of cold induced urticaria refractory to
      conventional antihistamine-type therapy would respond to treatment with
      sympathomimetic amines. METHODS: Dextroamphetamine sulfate (15 mg) extended
      release capsules were prescribed to be taken daily in the morning. RESULTS: The
      cold-induced urticaria completely disappeared and antihistamine therapy was
      discontinued. CONCLUSIONS: Treatment of chronic refractory cold-induced urticaria
      effectively responds to treatment with sympathomimetic amines similar to other
      cases of chronic refractory urticaria that are not merely cold induced.
      Manifestation of idiopathic orthostatic edema, a condition predominantly of
      women, should always be considered in the differential diagnosis of baffling
      medical conditions.

PMID- 21077536
TI  - Huge endometriosis presenting like an ovarian tumor: CT appearance.
AB  - A 32-year-old female with a clinical history of abdominal swelling underwent CT
      of the abdomen. A huge biloculated cystic mass with a mural nodule in the
      abdominal and pelvic region was seen. The lesion showed slightly homogeneous
      enhancement. The imaging findings suggested an ovarian tumor. Histopathological
      evaluation after surgical resection revealed that the lesion was a bilateral
      ovarian endometriosis.

PMID- 21077537
TI  - Case report: sacral parasitic twins.
AB  - INTRODUCTION: Sacral parasitic twins originate from one fertilized ovum and they
      have one placenta and the same sex. CASE REPORT: A 23-year-old woman was referred
      to our clinic. Examination by touch revealed a mass that was in the sacral region
      but the borders could not be fully examined. The solid mass, which was conjoined
      to the sacrum, had a soft texture. The infant's appearance was macroscopically
      normal. When the mass was examined by palpation, there were structures which felt
      like extremities. The mass was 20 x 11 x 9 cm in size. CONCLUSION: The
      differential diagnosis should include sacrococcygeal teratoma. In our case the
      differential diagnosis was done by histopathologic findings. This case, which
      involved a tumoral formation at the sacral region in the antenatal period, was
      detected during delivery. A sacral parasite is a rarely seen phenomenon and as
      such the diagnostic information of this case could be useful.

PMID- 21077538
TI  - Screening is a two-way street.

PMID- 21077539
TI  - Reform promises dollars, but not soon enough.

PMID- 21077540
TI  - Coalition weathers a storm.

PMID- 21077541
TI  - An option for tight training budgets.

PMID- 21077542
TI  - Establishing rapport in telehealth.

PMID- 21077543
TI  - Telepsychiatry's benefits are HD clear.

PMID- 21077544
TI  - An assault on trauma and addiction.

PMID- 21077545
TI  - Peer specialists can prevent suicides.

PMID- 21077546
TI  - Can design promote healing?

PMID- 21077547
TI  - Ketamine: a fast-acting antidepressant?

PMID- 21077548
TI  - Focus on 'can' leads CMHC to success.

PMID- 21077549
TI  - Making mobile knowledges. The educational cruises of the Revue Generale des
      Sciences Pures et Appliquees, 1897-1914.
AB  - Over the past few years there has been an increasing acknowledgment that all
      knowledge is "sited knowledge." While place, mobility, and travel have become
      central issues in the history (and geography) of science, much of the discussion
      has nevertheless revolved around "formal scientific knowledge." This essay
      focuses on a specific type of popular "mobile" scientific knowledge making that
      emerged in the last decades of the nineteenth century: the educational cruise. In
      particular, it considers a series of voyages d'etude organized by the French
      scientific periodical Revue Generale des Sciences Pures et Appliquees between
      1897 and 1914 that were open to the general public. It examines both the ways and
      the spaces in which knowledge was produced and the type of knowledge that was
      produced.

PMID- 21077550
TI  - Hearing the irrational: music and the development of the modern concept of
      number.
AB  - Because the modern concept of number emerged within a quadrivium that included
      music alongside arithmetic, geometry, and astronomy, musical considerations
      affected mathematical developments. Michael Stifel embedded the then-paradoxical
      term "irrational numbers" (numerici irrationales) in a musical context (1544),
      though his philosophical aversion to the "cloud of infinity" surrounding such
      numbers finally outweighed his musical arguments in their favor. Girolamo Cardano
      gave the same status to irrational and rational quantities in his algebra (1545),
      for which his contemporaneous work on music suggested parallels and empirical
      examples. Nicola Vicentino's attempt to revive ancient "enharmonic" music (1555)
      required and hence defended the use of "irrational proportions" (proportiones
      inrationales) as if they were numbers. These developments emerged in richly
      interactive social and cultural milieus whose participants interwove musical and
      mathematical interests so closely that their intense controversies about ancient
      Greek music had repercussions for mathematics as well. The musical interests of
      Stifel, Cardano, and Vicentino influenced their respective treatments of
      "irrational numbers." Practical as well as theoretical music both invited and
      opened the way for the recognition of a radically new concept of number, even in
      the teeth of paradox.

PMID- 21077552
TI  - Making knowledge: history, literature, and the poetics of science.
AB  - As a field of study, literature and science has gradually expanded to encompass
      both the impact of science on literary culture and the literary-linguistic
      practices intrinsic to the production of scientific knowledge. Such
      transformations both reinforce and fundamentally recalibrate the detailed
      attention focused on scientific practice by historians of science since the
      1980s. As a result, this essay and the Focus section it introduces suggest that
      history of science and literature and science are, in fact, interdependent
      fields. Attention to their convergences will yield better understanding of the
      performative dimensions of scientific practices and thence of science itself as a
      form of making of knowledge of things and events in the world of nature. Science
      as a form of making involves the convergence of things, material practices, and a
      panoply of meaningful artifacts-instruments of thought and action-that refuse any
      simple dichotomy between "text" and "action."

PMID- 21077551
TI  - Scientific biography, cognitive deficits, and laboratory practice. James McKeen
      Cattell and early American experimental psychology, 1880-1904.
AB  - Despite widespread interest in individual life histories, few biographies of
      scientists make use of insights derived from psychology, another discipline that
      studies people, their thoughts, and their actions. This essay argues that recent
      theoretical work in psychology and tools developed for clinical psychological
      practice can help biographical historians of science create and present fuller
      portraits of their subjects' characters and temperaments and more nuanced
      analyses of how these traits helped shape their subjects' scientific work. To
      illustrate this thesis, the essay examines the early career of James McKeen
      Cattell--an influential late nineteenth- and early twentieth-century experimental
      psychologist--through a lens offered by psychology and argues that Cattell's
      actual laboratory practices derived from an "accommodation" to a long-standing
      "cognitive deficit." These practices in turn enabled Cattell to achieve more
      precise experimental results than could any of his contemporaries; and their
      students readily adopted them, along with their behavioral implications. The
      essay concludes that, in some ways, American psychology's early twentieth-century
      move toward a behavioral understanding of psychological phenomena can be traced
      to Cattell's personal cognitive deficit. It closes by reviewing several
      "remaining general questions" that this thesis suggests.

PMID- 21077553
TI  - Modifiable futures: science fiction at the bench.
AB  - Science fiction remains an alien dimension of the history of science. Historical
      and literary studies of science have become increasingly attentive to various
      "literary technologies" in scientific practice, the metaphorical features of
      scientific discourse, and the impact of popular science writing on the social
      development of scientific knowledge. But the function of science fiction and even
      literature as such in the history of scientific and technological innovation has
      often been obscured, misconstrued, or repudiated owing to conventional notions of
      authorship, influence, and the organic unity of texts. The better to address
      those close encounters where scientific practice makes use of speculative
      fiction, this essay proposes that we instead analyze such exchanges as processes
      of appropriation, remixing, and modification.

PMID- 21077554
TI  - Science surveys and histories of literature: reflections on an uneasy kinship.
AB  - With their common focus on narrative, literary scholars and historians of science
      share a close relationship with language and can offer each other valuable
      interpretive insights. Particularly revealing in each field are scientists' and
      literary writers' changing uses of metaphor, which is critical to each kind of
      scholarship since both disciplines place such a high value on cultural context.
      Any cross-disciplinary help, however, needs to take into account the essential
      differences between the fields: contrasting views of what constitutes evidence
      and varying relationships with the past. Since both kinds of scholarship involve
      creating as well as analyzing narratives, each field has developed its own sense
      of pacing and significance, and their differing approaches to truth deserve
      respect.

PMID- 21077555
TI  - Lessons from literature for the historian of science (and vice versa):
      reflections on "form".
AB  - This essay surveys recent discussion of the problem of form in literary studies,
      identifies several ways in which the notion of form might be expanded, and
      suggests ways in which such an expanded category of form might be useful to
      historians of science and literary critics alike.

PMID- 21077556
TI  - Of atoms, oaks, and cannibals; or, more things that talk.
AB  - While literary works are often treated as museum pieces, an alternative Romantic/
      Pragmatic aesthetic emphasizes instead the rootedness of all texts in lived
      experience. This suggests that both literary and scientific texts may be
      approached as performances that weave together discursive and material elements,
      giving language to matter, both making, and becoming, "things that talk." Three
      authors are contrasted: Emerson uses natural objects as metaphors to complete his
      thought; Thoreau uses natural objects as mediators who enroll him to speak for
      them in the name of a wider ecology; Humboldt attempts to enroll nonhumans,
      namely cannibals, into the global civil community by asking them to speak for
      themselves. The resulting quandary unsettles the Cartesian boundary between human
      and nonhuman, subject and object; as scholars divided by this boundary, we must
      multiply our own relations, the better to understand the ties that bind us into
      the common project of building the Cosmos.

PMID- 21077557
TI  - Eloges: Ralph Colp, 1924-2008.

PMID- 21077558
TI  - Eloges: Karin Figala, 1938-2007.

PMID- 21077559
TI  - Eloges: David Charles Gooding, 1947-2009.

PMID- 21077560
TI  - Motorcycle conspicuity: effects of age and daytime running lights.
AB  - OBJECTIVE: This study investigated variables that may contribute to motorcycle
      conspicuity within a high-fidelity simulated environment. The variables included
      motorcycle lighting, vehicular daytime running lights (DRLs), and age of the
      driver of the other vehicle. BACKGROUND: Research suggests that decreased levels
      of conspicuity associated with riding a small two-wheeled vehicle reduce the
      ability of other drivers to detect and respond to that vehicle effectively. This
      lack of conspicuity is often responsible for the frequent injuries and fatalities
      incurred by motorcycle riders. METHOD: The 75 participants who took part in this
      study watched a series of video clips of roadway traffic and were asked to
      indicate when they saw a hazardous situation, such as the presence of
      pedestrians, motorcycles, or traffic cones. Both motorcycle and following-vehicle
      lights were manipulated, and participant reaction times were collected and
      analyzed. RESULTS: Analyses indicated main effects for all three variables as
      well as interaction effects between motorcycle lighting and vehicle-following
      conditions. Overall, findings showed a link between DRLs and the effective
      detection of motorcycles and suggested that age-related changes affect the
      ability to detect and respond to a motorcycle effectively. CONCLUSION: Although
      our laboratory findings corroborated previous correlational studies, further
      research in real-world settings, such as those with high-density traffic or under
      adverse environmental conditions, needs to be conducted. APPLICATION: Potential
      applications of this research include the assessment of appropriate lighting
      technology to enhance conspicuity of motorcycles and reduce the high rate of
      fatalities and injuries related to motorcycle crashes.

PMID- 21077561
TI  - An eye movement analysis of the effect of interruption modality on primary task
      resumption.
AB  - OBJECTIVE: We examined the effect of interruption modality (visual or auditory)
      on primary task (visual) resumption to determine which modality was the least
      disruptive. BACKGROUND: Theories examining interruption modality have focused on
      specific periods of the interruption timeline. Preemption theory has focused on
      the switch from the primary task to the interrupting task. Multiple resource
      theory has focused on interrupting tasks that are to be performed concurrently
      with the primary task. Our focus was on examining how interruption modality
      influences task resumption.We leverage the memory-for-goals theory, which
      suggests that maintaining an associative link between environmental cues and the
      suspended primary task goal is important for resumption. METHOD: Three
      interruption modality conditions were examined: auditory interruption with the
      primary task visible, auditory interruption with a blank screen occluding the
      primary task, and a visual interruption occluding the primary task. Reaction time
      and eye movement data were collected. RESULTS: The auditory condition with the
      primary task visible was the least disruptive. Eye movement data suggest that
      participants in this condition were actively maintaining an associative link
      between relevant environmental cues on the primary task interface and the
      suspended primary task goal during the interruption. CONCLUSION: These data
      suggest that maintaining cue association is the important factor for reducing the
      disruptiveness of interruptions, not interruption modality. APPLICATION:
      Interruption-prone computing environments should be designed to allow for the
      user to have access to relevant primary task cues during an interruption to
      minimize disruptiveness.

PMID- 21077562
TI  - Complacency and bias in human use of automation: an attentional integration.
AB  - OBJECTIVE: Our aim was to review empirical studies of complacency and bias in
      human interaction with automated and decision support systems and provide an
      integrated theoretical model for their explanation. BACKGROUND: Automation
      related complacency and automation bias have typically been considered separately
      and independently. METHODS: Studies on complacency and automation bias were
      analyzed with respect to the cognitive processes involved. RESULTS: Automation
      complacency occurs under conditions of multiple-task load, when manual tasks
      compete with the automated task for the operator's attention. Automation
      complacency is found in both naive and expert participants and cannot be overcome
      with simple practice. Automation bias results in making both omission and
      commission errors when decision aids are imperfect. Automation bias occurs in
      both naive and expert participants, cannot be prevented by training or
      instructions, and can affect decision making in individuals as well as in teams.
      While automation bias has been conceived of as a special case of decision bias,
      our analysis suggests that it also depends on attentional processes similar to
      those involved in automation-related complacency. CONCLUSION: Complacency and
      automation bias represent different manifestations of overlapping automation
      induced phenomena, with attention playing a central role. An integrated model of
      complacency and automation bias shows that they result from the dynamic
      interaction of personal, situational, and automation-related characteristics.
      APPLICATION: The integrated model and attentional synthesis provides a heuristic
      framework for further research on complacency and automation bias and design
      options for mitigating such effects in automated and decision support systems.

PMID- 21077563
TI  - Transitioning to future air traffic management: effects of imperfect automation
      on controller attention and performance.
AB  - OBJECTIVE: This study examined whether benefits of conflict probe automation
      would occur in a future air traffic scenario in which air traffic service
      providers (ATSPs) are not directly responsible for freely maneuvering aircraft
      but are controlling other nonequipped aircraft (mixed-equipage environment). The
      objective was to examine how the type of automation imperfection (miss vs. false
      alarm) affects ATSP performance and attention allocation. BACKGROUND: Research
      has shown that the type of automation imperfection leads to differential human
      performance costs. METHOD: Participating in four 30-min scenarios were 12 full
      performance-level ATSPs. Dependent variables included conflict detection and
      resolution performance, eye movements, and subjective ratings of trust and self
      confidence. RESULTS: ATSPs detected conflicts faster and more accurately with
      reliable automation, as compared with manual performance. When the conflict probe
      automation was unreliable, conflict detection performance declined with both miss
      (25% conflicts detected) and false alarm automation (50% conflicts detected).
      CONCLUSION: When the primary task of conflict detection was automated, even
      highly reliable yet imperfect automation (miss or false alarm) resulted in
      serious negative effects on operator performance. APPLICATION: The further in
      advance that conflict probe automation predicts a conflict, the greater the
      uncertainty of prediction; thus, designers should provide users with feedback on
      the state of the automation or other tools that allow for inspection and analysis
      of the data underlying the conflict probe algorithm.

PMID- 21077564
TI  - Hand and finger dexterity as a function of skin temperature, EMG, and ambient
      condition.
AB  - OBJECTIVE: This article examines the changes in skin temperature (finger, hand,
      forearm), manual performance (hand dexterity and strength), and forearm surface
      electromyograph (EMG) through 40-min, 11 degrees C water cooling followed by 15
      min, 34 degrees C water rewarming; additionally, it explores the relationship
      between dexterity and the factors of skin temperature, EMG, and ambient
      condition. BACKGROUND: Hand exposure in cold conditions is unavoidable and
      significantly affects manual performance. METHOD: Two tasks requiring gross and
      fine dexterity were designed, namely, nut loosening and pin insertion,
      respectively. The nested-factorial design includes factors of gender, participant
      (nested within gender), immersion duration, muscle type (for EMG), and location
      (for skin temperature). The responses are changes in dexterity, skin temperature,
      normalized amplitude of EMG, and grip strength. Finally, factor analysis and
      stepwise regression are used to explore factors affecting hand and finger
      dexterity. RESULTS: Dexterity, EMG, and skin temperature fell with prolonged
      cooling, but the EMG of the flexor digitorum superficialis remained almost
      unchanged during the nut loosening task. All responses but the forearm skin
      temperature recovered to the baseline level at the end of rewarming. The three
      factors extracted by factor analysis are termed skin temperature, ambient
      condition, and EMG. They explain approximately two thirds of the variation of the
      linear models for both dexterities, and the factor of skin temperature is the
      most influential. CONCLUSION: Sustained cooling and warming significantly
      decreases and increases finger, hand, and forearm skin temperature. Dexterity,
      strength, and EMG are positively correlated to skin temperature. Therefore,
      keeping the finger, hand, and forearm warm is important to maintaining hand
      performance. APPLICATION: The findings could be helpful to building safety
      guidelines for working in cold environments.

PMID- 21077565
TI  - Reliability of distal upper extremity posture matching using slow-motion and
      frame-by-frame video methods.
AB  - OBJECTIVE: The aim of this study was to determine the effects of video playback
      speed on posture matching reliability of the distal upper extremity. BACKGROUND:
      Video is frequently used in ergonomic assessments, yet there remains a need to
      determine the effects of viewing speed on posture observations. METHOD:
      Participants were 7 graduate students experienced with posture-based
      observational methods. Categorical posture scales were used to evaluate forearm
      pronation/supination, wrist flexion/extension, wrist radioulnar deviation,and
      hand activity from workplace video at three playback speeds (quarter, half, and
      real time). Wrist flexion/extension was also evaluated with a frame-by-frame
      video method. RESULTS: Posture counts increased with slower viewing speeds for
      the wrist and hand, but percentage durations in each posture category were
      similar for all methods. Posture matching interrater reliability scores increased
      with slow-motion video playback but remained low even for quarter-time video
      playback. The highest interrater scores were found in the frame-by-frame analysis
      of wrist flexion/extension for three posture categories (percentage agreement =
      84.9% +/- 1.3%; kappa = 0.54 +/- 0.02). CONCLUSION: Although slower video
      playback speeds increased the number of posture counts for the wrist and hand
      scales, percentage durations were similar, and reliability scores increased only
      slightly with slow-motion video playback. APPLICATION: Reviewing video using slow
      motion or frame-by-frame methods improves distal upper extremity posture matching
      reliability. However, ergonomic assessment tools based on percentage duration may
      not be appreciably enhanced by slowing viewing speed. Thus, the increased viewing
      time with slower playback should be justified with respect to assessment needs.

PMID- 21077566
TI  - Ergonomic factors related to drop-off detection with the long cane: effects of
      cane tips and techniques.
AB  - OBJECTIVE: This study examined the effect of cane tips and cane techniques on
      drop-off detection with the long cane. BACKGROUND: Blind pedestrians depend on a
      long cane to detect drop-offs. Missing a drop-off may result in falls or
      collision with moving vehicles in the street. Although cane tips appear to affect
      a cane user's ability to detect drop-offs, few experimental studies have examined
      such effect. METHOD: A repeated-measures design with block randomization was used
      for the study. Participants were 17 adults who were legally blind and had no
      other disabilities. Participants attempted to detect the drop-offs of varied
      depths using different cane tips and cane techniques. RESULTS: Drop-off detection
      rates were similar between the marshmallow tip (77.0%) and the marshmallow roller
      tip (79.4%) when both tips were used with the constant contact technique, p =
      .294. However, participants detected drop-offs at a significantly higher
      percentage when they used the constant contact technique with the marshmallow
      roller tip (79.4%) than when they used the two-point touch technique with the
      marshmallow tip (63.2%), p < .001. CONCLUSION: The constant contact technique
      used with a marshmallow roller tip (perceived as a less advantageous tip) was
      more effective than the two-point touch technique used with a marshmallow tip
      (perceived as a more advantageous tip) in detecting drop-offs. APPLICATION: The
      findings of the study may help cane users and orientation and mobility
      specialists select appropriate cane techniques and cane tips in accordance with
      the cane user's characteristics and the nature of the travel environment.

PMID- 21077567
TI  - Driver acceptance of false alarms to simulated encroachment.
AB  - OBJECTIVE: We investigated driver acceptance of alerts to left-turn encroachment
      incidents that do not produce a crash. If an event that produces a crash is the
      criterion for a "true" alert, all the alerts we studied are technically false
      alarms. Our aim was to inform the design of intersection-assist active safety
      systems. BACKGROUND: The premise of this study is that it may be possible to
      overcome driver resistance to alerts that are false alarms by designing systems
      to issue alerts when and only when drivers would expect and accept them. METHOD:
      Participants were passengers in a driving simulator that presented left-turn
      encroachment incidents. Participant point of view, the direction of encroachment,
      and postencroachment time (PET) were manipulated to produce 36 near-crash
      incidents. After viewing each incident, the participant rated the relative
      acceptability of a hypothetical alert to it. RESULTS: Repeated-measures ANOVA and
      logistic regression indicate that acceptability varies inversely with PET. At PET
      intervals less than 2.2 s, driver point of view and encroachment direction
      interact. At PET intervals more than 2.2 s, alerts to lateral encroachments are
      more acceptable than alerts to oncoming encroachments. CONCLUSION: Driver
      acceptance of alerts by active safety systems will be sensitive to context.
      APPLICATION: This study demonstrates the utility of eliciting subjective criteria
      to inform system design to match driver (user) expectations. Intersection-assist
      active safety systems will need to be designed to adapt to the interaction of
      driver point of view, the direction of encroachment, and PET.

PMID- 21077568
TI  - Electrophysiological approaches to psychopathology and the influence of
      lateralization.

PMID- 21077569
TI  - EEG alpha asymmetry in schizophrenia, depression, PTSD, panic disorder, ADHD and
      conduct disorder.
AB  - Models of laterality infer distinct aspects of EEG alpha asymmetry in clinical
      disorders, which has been replicated for over three decades. This biomarker now
      requires a more fine-grained assessment of its clinical utility as a diagnostic
      and treatment predictive marker. Here, within the same study we assessed resting
      brain laterality across six clinical disorders, for which deviant laterality has
      been implicated as core dysfunction. These disorders were evaluated in comparison
      to a large normative dataset (approximately 1,900) from the Brain Resource
      International Database. EEG alpha asymmetry was assessed in the frontocentral
      region, for resting Eyes Closed and Eyes Open conditions. Schizophrenia was
      characterized by significantly greater left lateralized alpha power than
      controls, indicating a deficit in left frontal activity at rest, which may relate
      to "disconnections" across wider fronto-temporal networks. The depression group
      showed a trend-level tendency towards the opposite pattern of greater right
      lateralized activity than controls. The remaining anxiety and behavioral
      disorders did not show any significant deviance in alpha asymmetry from the
      normative control group. However, at a non-significant level laterality for these
      groups was generally consistent with expected directions, suggesting a propensity
      towards a particular lateralization but still remaining within the normative
      range. Overall, the results of the current study indicate that EEG alpha
      asymmetry may show the most clinical utility as a biomarker for schizophrenia and
      depression in comparison to other clinical disorders.

PMID- 21077570
TI  - ERP generator patterns in schizophrenia during tonal and phonetic oddball tasks:
      effects of response hand and silent count.
AB  - Greater left than right reductions of P3 amplitude in schizophrenia during
      auditory oddball tasks have been interpreted as evidence of left-lateralized
      dysfunction. However, the contributions of methodological factors (response mode,
      stimulus properties, recording reference), which affect event-related potential
      (ERP) topographies, remain unclear. We recorded 31-channel ERPs from 23
      schizophrenic patients and 23 age- and gender-matched healthy controls (all right
      handed) during tonal and phonetic oddball tasks, varying response mode (left
      press, right press, silent count) within subjects. Performance accuracy was high
      in both groups but patients were slower. ERP generator patterns were summarized
      by temporal Principal Components Analysis (PCA; unrestricted Varimax) from
      reference-free current source density (CSD; spherical spline Laplacians)
      waveforms, which sharpen scalp topographies. CSD represents the magnitude of the
      radial current flow entering (source) and leaving (sink) the scalp. Both patients
      and controls showed asymmetric frontolateral and parietotemporal N2 sinks peaking
      at 240 ms and asymmetric parietal P3 sources (355 ms) for targets (tonal R > L,
      phonetic L > R), but frontocentral N2 sinks and parietal P3 sources were
      bilaterally reduced in patients. A response-related midfrontal sink and
      accompanying centroparietal source (560 ms) were highly comparable across groups.
      However, a superimposed left temporal source was larger for silent count compared
      to button press, and this difference was smaller in patients. In both groups,
      left or right press produced opposite, region-specific asymmetries originating
      from central sites, modulating the N2/P3 complex. The results suggest bilaterally
      reduced neural generators of N2 and P3 in schizophrenia during auditory oddball
      tasks, but both groups showed comparable topographic effects of task and response
      mode. However, additional working memory demands during silent count may
      partially overlap in time the generation of the N2/P3 complex and differentially
      affect the asymmetry of P3 subcomponents, particularly when employing
      conventional ERP measures.

PMID- 21077571
TI  - EEG hemispheric asymmetries during cognitive tasks in depressed patients with
      high versus low trait anxiety.
AB  - Studies of regional hemispheric asymmetries point to relatively less activity in
      left frontal and right posterior regions in depression. Anxiety was associated
      with increased right posterior activity, which may be related to arousal and, in
      anxious-depressed individuals, offset the posterior asymmetry typically seen in
      depression. These asymmetries have been indexed by resting EEG or inferred
      through the use of lateralized auditory and visual tasks (e.g., dichotic
      listening and chimeric faces). However, associations between regional EEG
      activity and neurocognitive function in depression or anxiety remain unclear. The
      present study used matched verbal (Word Finding) and spatial (Dot Localization)
      tasks to compare task-related alpha asymmetries in depressed patients grouped
      according to level of trait anxiety. EEG and behavioral performance were recorded
      from depressed patients with high anxiety (n = 14) or low anxiety (n = 14) and 21
      age- and education-matched healthy adults during the two tasks, and alpha power
      was averaged within each task. As predicted, the two patient groups exhibited
      opposite patterns of regional hemispheric alpha asymmetry. Greater right than
      left central-parietal activation was seen in the high-anxiety depressed group
      during the spatial task, whereas greater left than right frontal-central
      activation was found in the low-anxiety depressed group during the verbal task.
      Group differences in task performance were in the expected direction but did not
      reach statistical significance. These results are consistent with Heller's two
      dimensional model of depression and anxiety and highlight the sensitivity of task
      related EEG alpha in discriminating among subgroups of depressed patients
      differing in trait anxiety.

PMID- 21077572
TI  - EEG topography and tomography (LORETA) in diagnosis and pharmacotherapy of
      depression.
AB  - Earlier investigations suggested an involvement of the right hemisphere and the
      left prefrontal cortex (PFC) in the pathogenesis of depression. This paper
      presents our own electroencephalographic (EEG) topography and low-resolution
      brain electromagnetic tomography (LORETA) data obtained in unmedicated depressed
      patients, and the effects of two representative drugs of non-sedative and
      sedative antidepressants, i.e., citalopram (CIT) and imipramine (IMI), as
      compared with placebo in normal subjects. Sixty female menopausal syndrome
      patients with the diagnosis of a depressive episode without psychotic symptoms as
      well as 30 healthy controls were investigated. Concerning the effects of
      antidepressants, normal healthy subjects received single oral doses of 20 mg CIT,
      75 mg IMI and placebo p.o. A 3-min vigilance-controlled EEG and a 4-min resting
      EEG was recorded pre- and post-drug administration and analyzed by means of EEG
      mapping and LORETA. In the EEG mapping, depressed patients demonstrated a
      decrease in absolute power in all frequency bands, an augmentation of relative
      delta/theta and beta and a decrease in alpha activity as well as a slowing of the
      delta/theta centroid and an acceleration of the alpha and beta centroid, which
      suggests vigilance decrements. In the alpha asymmetry index, they showed right
      frontal hyper- and left frontal hypoactivation correlated with the Hamilton
      Depression Score (HAMD). LORETA predominantly revealed decreased power in the
      theta and alpha-1 frequency band. Negative correlations between theta power and
      the HAMD were observed in the ventro-medial PFC, the bilateral rostral anterior
      cingulate cortex (ACC) and the left insular cortex; between alpha-1 power and the
      HAMD in the right PFC. In the EEG mapping of antidepressants, 20 mg CIT showed
      mainly activating, 75 mg IMI partly sedative properties. LORETA revealed that CIT
      increased alpha-2, beta-1, beta-2 and beta-3 power more over the right than over
      the left hemisphere. However, also a left temporal and frontal delta increase was
      observed. In conclusion, EEG topography and tomography of depressed menopausal
      patients demonstrated a right frontal hyper- and left frontal hypoactivation in
      the alpha asymmetry index as well as a vigilance decrease, with a right
      hemispheric preponderance. Within antidepressants at least 2 subtypes may be
      distinguished from the electrophysiological point of view, a non-sedative and a
      sedative. LORETA identifies cerebral generators responsible for the pathogenesis
      of depression as well as for the mode of action of antidepressants.

PMID- 21077573
TI  - Sodium amytal testing and the laterality of emotion.
AB  - In this paper, the results of studies that have used the intracarotid sodium
      amytal (amobarbital) test to examine hemispheric lateralization of emotional
      expression has been reviewed. The important findings are that the emotional
      states are dissociated from the neurological effects (aphasia, hemiplegia), and
      occur later, when the electroencephalogram (EEG) is showing evidence of
      activation. The effects of left hemisphere barbiturization are less clear than
      those of the right hemisphere, and there is good concordance that the latter lead
      to states of alteration in mood or euphoria.

PMID- 21077574
TI  - Some evidence of bilateral speech representation in sinistrals.
AB  - The information provided by pre and post-operative surface EEG, cortical EEG,
      cortical stimulation, intracarotid barbiturization, psychometric testing and
      ictal semiology are integrated in order to define the speech regions. The three
      patients described are predominantly left handed and left cerebral hemisphere
      dominant, all with right hemisphere epilepsy. All are considered to have bi
      lateral speech representation to account for dysphasia during cortical
      stimulation in all three and ictal or post ictal dysphasia in the first two and
      post-operative dysphasia in the first and third. Some of the evidence that
      supports the possibility of bi-lateral speech representation is discussed.

PMID- 21077575
TI  - EEG analysis of male to female transsexuals: discriminant function and source
      analysis.
AB  - A small series of consecutive, unmedicated male to female transsexuals were
      studied before hormonal treatment and prior to reassignment surgery. Quantitative
      EEG and LORETA source localization in the Eyes Open and Eyes Closed conditions
      were carried out, and they were compared to sinistral/ambilateral male and female
      controls, as the transsexual group was overwhelmingly sinistral. Discriminant
      function analysis and source localization showed that the transsexual group was
      similar to female heterosexual controls, with increased sources in the right
      hemisphere in the fast frequencies.

PMID- 21077576
TI  - From public to occupational health: towards an inverse push-pull paradigm in
      nanotechnologies innovation.
AB  - Nanotechnologies are an important set of new technologies no longer at a very
      early stage in their development. The financial support for R&D in this domain is
      greater than a few Giga Euros/year for innovation and considerably lower (less
      than 1-2%) for risk management. At the factory level, As Low As Reasonably
      Achievable (ALARA) methods have to be used in order to protect workers against
      possible exposure. New "short-term" toxicological studies show that nano
      particles are seldom exempt of effects in humans... Thus, for the general
      population, more and more anxious about the future, nanotechnologies are the
      object of numerous debates. Ultimately, the population is asking governmental
      bodies to take the required preventive measures. Social pressure is now initiated
      by the public towards innovative industries, which have to prove, before the
      marketing stage, the absence of any risk for the users and demonstrate a safety
      driven governance.

PMID- 21077577
TI  - The ethical challenges of the occupational physician in our time.
AB  - An increasing interest in professional ethics is observed among occupational
      health professionals. To this may contribute the ongoing financial crisis of
      world economy. The moral development, induced i.a. by the Nuremberg trials in
      1947 has probably contributed to a changing moral landscape. Within health
      professions, including many categories of occupational health professionals there
      is an increasing awareness of the needs to revisit points of departure in
      building up ethical competence to and prepare their members for tasks in the
      Labour market. Selected topics will be commented on in respect to their
      challenges to occupational professional health ethics. Widening of perspectives
      of Ethics in traditional Hippocratic medical ethics issues related to
      requirements of confidentiality and informed consent.

PMID- 21077578
TI  - Deepwater Horizon oil rig exploded.

PMID- 21077579
TI  - Interview with Rear Admiral Eleanor Valentin, FACHE, Commander, U.S. Navy
      Medicine Support Command and Director, Navy Medical Service Corps. Inverview by
      Stephen J O'Connor.

PMID- 21077580
TI  - Cost-containment and cost-management strategies.

PMID- 21077581
TI  - A randomized trial of telemonitoring heart failure patients.
AB  - The purpose of this study was to measure the ability of telemonitoring to reduce
      hospital days and total costs for Medicare managed care enrollees diagnosed with
      heart failure. Patients were recruited and randomly assigned for six months to
      either telemonitoring or standard care. Telemonitoring transmitted vital signs
      and clinical alerts daily to a central nursing station. Utilization of covered
      services was analyzed for the six-month telemonitoring period to test for
      hypothesized reductions in hospital days and changes in utilization of the
      emergency department (ED), urgent care, and primary care. Negative binomial
      regressions adjusted for gender, age, co-occurring diabetes, co-occurring chronic
      obstructive pulmonary disease, and residence neighborhood were used to analyze
      units of service, and two-part (hurdle) multivariable models were used for
      expenditures. The main finding was a tendency for lower total number of hospital
      days for patients assigned to telemonitoring. Results for other covered services
      were generally consistent with hypothesized direction and magnitude; however,
      statistical power was reduced because of lower-than-expected recruitment rates
      into the study. Within a managed-care environment, telemonitoring appears to
      facilitate better ambulatory management of heart failure patients, including
      fewer ED visits, which were offset by more frequent primary care and urgent care
      visits.

PMID- 21077582
TI  - Hospital-affiliated and hospital-owned retail clinics: strategic opportunities
      and operational challenges.
AB  - Retail clinics have experienced an exponential growth in the last few years.
      While the majority of retail clinics are freestanding, venture-backed companies
      affiliated with retail hosts, an increasing number of hospital systems have
      decided to develop their own retail clinics or partner with existing national
      companies. Using a stakeholder approach, the purpose of this article is to assess
      the strategic considerations behind these decisions and the operational
      challenges associated with them and to use the results to develop a questionnaire
      that can be applied in future research in a national sample of healthcare
      executives. We conducted eight in-depth interviews with administrative and
      clinical leaders in seven hospital systems across the United States that have or
      had a relationship with retail clinics in the last three years. Our findings show
      that the hospital systems' association with retail clinics involves two main
      models: an affiliation with retail chains that operate the clinics and ownership
      of the clinics with an arms-length relationship with the retail chain. Hospital
      systems are engaging in these relationships for several strategic reasons: to
      increase market share through enhanced referrals to physician offices and
      hospitals, to become closer to consumers, and to experiment with nontraditional
      ways of delivering health care. Operational challenges included physician
      resistance and skepticism, poor financial performance, people's perception of
      retail clinics, staffing issues, and the newness of the business model. Six out
      of eight respondents thought that hospital affiliation with/ownership of retail
      clinics is a trend that is here to stay, although many provided caveats and
      stipulations. Further research is needed to provide more evidence about this
      emerging way of healthcare delivery.

PMID- 21077583
TI  - From the perspective of CEOs: what motivates hospitals to embrace cultural
      competence?
AB  - The quality domains of patient-centered and equitable care are increasingly
      relevant to today's healthcare leaders as hospitals care for patients with
      increasingly diverse cultural and linguistic needs. Hospital leaders face
      substantial tensions in defining their organization's strategic priorities to
      improve care for diverse populations with limited resources, increased
      competition, and complex regulatory and accreditation requirements. We sought to
      understand what motivates hospitals to focus on and commit resources to
      supporting the delivery of culturally competent care by analyzing interviews with
      chief executive officers (CEOs) in 60 hospitals across the United States.
      Hospital CEOs in our study most often embraced cultural competence efforts
      because doing so helped them achieve the organization's mission and priorities
      and/ or meet the needs of a particular patient population. Less often, they were
      motivated by perceived benefits and legal or regulatory issues. Many CEOs
      articulated a link between quality and cultural competence, and a smaller number
      went on to link cultural competence efforts to improved financial outcomes
      through cost savings, increased market share, and improved efficiency of care.
      However, the link between quality and cultural competence is still in the early
      stages. Fortunately, frameworks for hospitals to adopt and steps that hospitals
      can take to improve the quality of care for all patients have been identified.
      They begin with a commitment from hospital leaders based on understanding the
      needs of patients and communities and are propelled by data that reveal the
      impact of efforts to improve care. Leaders must communicate and shepherd
      organizations to align the congruence between improvement efforts and business
      strategies.

PMID- 21077584
TI  - Emerging technologies in healthcare: navigating risks, evaluating rewards.
AB  - The purpose of this prescriptive research is to help decision makers become
      better informed about three technologies emerging in the healthcare arena by
      providing a basic description of the technology and describing their current
      applications, future healthcare deployment, potential risks, and related
      managerial issues. Two of the technologies, radio frequency identification (RFID)
      and global positioning systems (GPS), are currently available to healthcare
      organizations and appear capable of decreasing cost but may require significant
      initial investment and have disruptive potential. The third technology,
      nanotechnology, has limited current use but may revolutionize both the delivery
      of medicine and hospital infrastructure management. With cautious attention to
      managerial issues and meticulous attention to implementation details, healthcare
      organizations that can successfully navigate the coming technologically driven
      paradigm shifts will emerge more resilient organizations.

PMID- 21077585
TI  - Quantum-chemical study on the bioactive conformation of epothilones.
AB  - Herein, I report a DFT study on the bioactive conformation of epothilone A based
      on the analysis of 92 stable conformations of free and bound epothilone to a
      reduced model of tubulin receptor. The equilibrium structures and relative
      energies were studied using B3LYP and X3LYP functionals and the 6-31G(d) standard
      basis set, which was considered appropriate for the size of the systems under
      study. Calculated relative energies of free and bound epothilones led me to
      propose a new model for the bioactive conformation of epothilone A, which
      accounts for several structure-activity data.

PMID- 21077586
TI  - Polytypism, disorder, and anion exchange properties of divalent ion (Zn, Co)
      containing bayerite-derived layered double hydroxides.
AB  - Incorporation of Zn(2+) into bayerite results in the formation of a cation
      ordered layered double hydroxide (LDH) of monoclinic symmetry in which about half
      the vacancies of Al(OH)(3) are occupied by Zn(2+) giving rise to positively
      charged layers. Charge compensation takes place by the incorporation of sulfate
      ions in the interlayer region. Structure refinement reveals that the adjacent
      layers in the crystal are related by a 2(1) axis (we call it 2M(1) polytype) with
      sulfate coordinating in the D(2d) symmetry in the interlayer region. Another
      polytype in which adjacent layers are related by a 2-fold axis (2M(2) polytype)
      can also be envisaged. Faulted crystals arising from intergrowths of the 2M(2)
      polytype within the 2M(1) structure were also obtained. These bayerite-based LDHs
      have a distinctly different interlayer chemistry when compared to the better
      known brucite-based LDHs, in that they have a strong affinity for tetrahedral
      ions such as SO(4)(2-), CrO(4)(2-), and MoO(4)(2-) and a poor affinity for
      CO(3)(2-) ions. These observations have implications for the use of LDHs in
      applications related to chromate sorption.

PMID- 21077587
TI  - Reactivity of a phospholipid monolayer model under periodic boundary conditions:
      a density functional theory study of the Schiff base formation between
      phosphatidylethanolamine and acetaldehyde.
AB  - A mechanism for the formation of the Schiff base between an acetaldehyde and an
      amine-phospholipid monolayer model based on Dmol3/density functional theory
      calculations under periodic boundary conditions was constructed. This is the
      first time such a system has been modeled to examine its chemical reactivity at
      this computation level. Each unit cell contains two phospholipid molecules, one
      acetaldehyde molecule, and nine water molecules. One of the amine-phospholipid
      molecules in the cell possesses a neutral amino group that is used to model the
      nucleophilic attack on the carboxyl group of acetaldehyde, whereas the other has
      a charged amino group acting as a proton donor. The nine water molecules form a
      hydrogen bond network along the polar heads of the phospholipids that facilitates
      very fast proton conduction at the interface. Using periodic boundary conditions
      afforded proton transfer between different cells. The reaction takes place in two
      steps, namely, (1) formation of a carbinolamine and (2) its dehydration to the
      Schiff base. The carbinolamine is the primary reaction intermediate, and
      dehydration is the rate-determining step of the process, consistent with
      available experimental evidence for similar reactions. On the basis of the
      results, the cell membrane surface environment may boost phospholipid glycation
      via a neighboring catalyst effect.

PMID- 21077588
TI  - A computational chemistry study on friction of h-MoS2. Part II. Friction
      anisotropy.
AB  - In this work, the friction anisotropy of hexagonal MoS(2) (a well-known lamellar
      compound) was theoretically investigated. A molecular dynamics method was adopted
      to study the dynamical friction of two-layered MoS(2) sheets at atomistic level.
      Rotational disorder was depicted by rotating one layer and was changed from 0
      degrees  to 60 degrees , in 5 degrees  intervals. The superimposed structures
      with misfit angle of 0 degrees  and 60 degrees  are commensurate, and others are
      incommensurate. Friction dynamics was simulated by applying an external pressure
      and a sliding speed to the model. During friction simulation, the incommensurate
      structures showed extremely low friction due to cancellation of the atomic force
      in the sliding direction, leading to smooth motion. On the other hand, in
      commensurate situations, all the atoms in the sliding part were overcoming the
      atoms in counterpart at the same time while the atomic forces were acted in the
      same direction, leading to 100 times larger friction than incommensurate
      situation. Thus, lubrication by MoS(2) strongly depended on its interlayer
      contacts in the atomic scale. According to part I of this paper [Onodera, T., et
      al. J. Phys. Chem. B 2009, 113, 16526-16536], interlayer sliding was source of
      friction reduction by MoS(2) and was originally derived by its material property
      (interlayer Coulombic interaction). In addition to this interlayer sliding, the
      rotational disorder was also important to achieve low friction state.

PMID- 21077590
TI  - Spectroscopic probing of the microenvironment in a protein-surfactant assembly.
AB  - The effect of the anionic surfactant sodium dodecyl sulfate (SDS) on the protein
      human serum albumin (HSA) was studied using steady-state spectroscopy, time
      resolved measurements, and circular dichroism spectroscopy. The binding of SDS to
      the domain IIA of HSA, housing the single tryptophan amino acid residue (Trp214),
      was monitored, and it was found that this addition of the surfactant takes place
      in a sequential manner depending upon the concentration of the added surfactant.
      Both fluorescence intensity and lifetimes of HSA decreased with the increasing
      concentration of SDS, and the surfactant molecules serve the role of a quencher
      for the fluorescence of Trp214. Circular dichroism data also support the
      structural changes induced by SDS. The 17 disulfide bridges present in HSA
      provide the necessary structural rigidity to the protein. Stern-Volmer plots and
      thermodynamic parameters have been used to characterize the sequential binding of
      SDS to HSA, and these parameters not only confirm that the binding is spontaneous
      in nature but also is quite strong, depending on the concentration of the added
      surfactant.

PMID- 21077589
TI  - Computational determination of binding structures and free energies of
      phosphodiesterase-2 with benzo[1,4]diazepin-2-one derivatives.
AB  - Phosphodiesterase-2 (PDE2) is a key enzyme catalyzing hydrolysis of both cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) that
      serve as intracellular second messengers. PDE2 has been recognized as an
      attractive drug target, and selective inhibitors of PDE2 are expected to be
      promising candidates for the memory enhancer, antidepressant, and anxiolytic
      agent. In the present study, we examined the detailed binding structures and free
      energies for PDE2 interacting with a promising series of inhibitors, i.e.,
      benzo[1,4]diazepin-2-one derivatives, by carrying out molecular docking,
      molecular dynamics (MD) simulations, binding free energy calculations, and
      binding energy decompositions. The computational results provide valuable
      insights into the detailed enzyme-inhibitor binding modes including important
      intermolecular interactions, e.g., the pi-pi stacking interactions with the
      common benzo[1,4]diazepin-2-one scaffold of the inhibitors, hydrogen bonding and
      hydrophobic interactions with the substituents on the benzo[1,4]diazepin-2-one
      scaffold. Future rational design of new, more potent inhibitors of PDE2 should
      carefully account for all of these favorable intermolecular interactions. By use
      of the MD-simulated binding structures, the calculated binding free energies are
      in good agreement with the experimental activity data for all of the examined
      benzo[1,4]diazepin-2-one derivatives. The enzyme-inhibitor binding modes
      determined and the agreement between the calculated and experimental results are
      expected to be valuable for future rational design of more potent inhibitors of
      PDE2.

PMID- 21077592
TI  - Glass dynamics and anomalous aging in a family of ionic liquids above the glass
      transition temperature.
AB  - The present paper reports the results of a systematic rheological study of the
      dynamic moduli of 1-butyl 3-methylimidazolium tetrafluoroborate ([Bmim][BF(4)]),
      1-butyl 3-methylimidazolium hexafluorophosphate ([Bmim][PF(6)]), and 1-ethyl 3
      methylimidazolium ethylsulfate ([Emim][EtSO(4)]) in the vicinity of their
      respective glass transition temperatures. The results show an anomalous aging in
      that the dynamic and the low shear rate viscosities decrease with time at
      temperatures near to, but above, the glass transition temperature, and this is
      described. The samples that are aged into equilibrium obey the time-temperature
      superposition principle, and the shift factors and the viscosities follow classic
      super-Arrhenius behaviors with intermediate fragility values as the glass
      transition is approached. Similar experiments using a high-purity [Bmim][BF(4)]
      show that using a higher purity of the ionic liquid, while changing absolute
      values of the properties, does not eliminate the anomalous aging response. The
      data are also analyzed in a fashion similar to that used for polymer melts, and
      we find that these ionic liquids do not follow, for example, the Cox-Merz
      relationship between the steady shear viscosity and the dynamic viscosity.

PMID- 21077593
TI  - Nanosecond-regime correlation time scales for equilibrium protein structural
      fluctuations of metal-free cytochrome c from picosecond time-resolved
      fluorescence spectroscopy and the dynamic Stokes shift.
AB  - We used picosecond time-resolved fluorescence spectroscopy to characterize the
      fluorescence Stokes shift (FSS) response function of metal-free (or free-base,
      fbCytc) cytochrome c under the solution conditions that favor the native states
      of ferricytochrome c (FeCytc) and Zn(II)-substituted cytochrome c (ZnCytc). The
      intrinsic porphyrin chromophore serves in these experiments as a fluorescent
      probe of the structural fluctuations of the surrounding protein and solvent.
      Demetalation of the porphyrin destabilizes the folded structure of cytochrome c
      owing to the loss of the axial metal-histidine and metal-methionine bonds. Thus,
      these experiments examine how the time scales detected in a dynamic solvation
      experiment in a chromoprotein report changes in the character of motion. The FSS
      response function in fbCytc in water and pH 7 is well described by a
      biexponential response over the 100 ps to 50 ns regime with time constants of 1.4
      and 9.1 ns; under similar conditions, ZnCytc exhibits a biexponential FSS
      response with time constants of 250 ps and 1.5 ns [Lampa-Pastirk and Beck, J.
      Phys. Chem. B 2004, 108, 16288]. These time constants correspond, respectively,
      to the correlation time scales for motions of the hydrophobic core and the
      solvent-contact layer of the protein. Both of the time constants observed in
      fbCytc are further lengthened upon addition of glycerol to the external solvent
      so that a significant fraction of the protein dynamics is rendered effectively
      static on the fluorescence time scale. The solvation reorganization energy, the
      time-integrated Stokes shift of the fluorescence spectrum, is reduced by about a
      third to 33 cm(-1) in 50% glycerol from 43 cm(-1) in water. These results are
      interpreted structurally using a model for Brownian diffusive motion with
      thermally activated barrier crossings on the protein-folding energy landscape.
      The results suggest that the mean-squared deviations of the structural
      fluctuations exhibited by fbCytc are nearly a factor of 10 larger than those of
      ZnCytc. This conclusion is consistent with the suggestion that fbCytc assumes a
      dynamic, partially unfolded structure with some of the characteristics of a
      molten globule.

PMID- 21077591
TI  - Slow conformational motions that favor sub-picosecond motions important for
      catalysis.
AB  - It has been accepted for many years that functionally important motions are
      crucial to binding properties of ligands in such molecules as hemoglobin and
      myoglobin. In enzymatic reactions, theory and now experiment are beginning to
      confirm the importance of motions on a fast (ps) time scale in the chemical step
      of the catalytic process. What is missing is a clear physical picture of how slow
      conformational fluctuations are related to the fast motions that have been
      identified as crucial. This paper presents a theoretical analysis of this issue
      for human heart lactate dehydrogenase. We will examine how slow conformational
      motions bring the system to conformations that are distinguished as catalytically
      competent because they favor specific fast motions.

PMID- 21077594
TI  - Complexes of molecular and ionic character in the same matrix layer: infrared
      studies of the sulfuric acid/ammonia system.
AB  - The atmospherically important interaction products of sulfuric acid and ammonia
      molecules have been firstly observed by matrix isolation Fourier transform
      infrared spectroscopy (MIS-FTIR). Infrared spectra of solid argon matrix layers,
      in which both H(2)SO(4) and NH(3) molecules were entrapped as impurities, were
      analyzed for bands not seen in matrix layers containing either of the parent
      molecules alone. Results were interpreted on the basis of spectral changes,
      experimental conditions, and semiempirically scaled frequencies from the
      B3LYP/aug-cc-pVTZ and B3LYP/aug-cc-pVQZ calculations. Bands were assigned to
      complexes of the H(2)SO(4).NH(3) and H(2)SO(4).[NH(3)](2) general formulas. They
      differ significantly: the 1:1 H(2)SO(4).NH(3) complex is a strongly hydrogen
      bonded complex, an analogue of the H(2)SO(4).H(2)O complex, studied previously.
      For the 1:2 H(2)SO(4).[NH(3)](2) complex, spectral results indicate an almost
      complete proton transfer forming a complex of essentially the two ionic moieties
      HSO(4)(-) and [H(3)N...H...NH(3)](+), an analogue of the [H(2)O...H...OH(2)](+)
      "Zundel ion".

PMID- 21077595
TI  - Enhanced conformational sampling of peptides via reduced side-chain and solvent
      masses.
AB  - When only equilibrium thermodynamics or averages of position-dependent functions
      in classical molecular dynamics calculations are sought, the choice of the atomic
      masses in the Hamiltonian becomes irrelevant. Consequently, the masses can be
      used as free parameters to help improve conformational sampling efficiency in the
      spirit of Bennett's mass-tensor dynamics (Bennett, C. H. J. Comput. Phys. 1975,
      19, 267.). Here we report on the effect of reducing side-chain and solvent masses
      on the folding behavior of a 9-residue hairpin-forming peptide in solution. A
      physical motivation for reducing the solvent mass is an effective reduction in
      solvent viscosity. Side-chain mass scaling is motivated by the idea of solvent
      potentials of mean force which are employed in select coarse-grained protein
      models. In the limit of very large mass differences, the mass reduction
      effectively creates an adiabatic decoupling between solvent, side-chain, and
      backbone motions, so that both the backbone and side chains move on the
      instantaneous solvent potential of mean force (PMF) surface, and the backbone
      additionally moves on the side-chain PMF. Because of the arbitrariness in the
      choice of masses, this limit only needs to be reached approximately in practice.
      In particular, we show that a 10-fold reduction in solvent masses and a side
      chain mass scale that is intermediate between the scaled solvent and the backbone
      lead to a quantitative enhancement in conformational sampling.

PMID- 21077596
TI  - Nitrile-rich coordination polymer
      (1)(infinity){[Fe(CH(3)CN)(4)(pyrazine)](ClO(4))(2)} exhibiting a HS ? LS
      transition.
AB  - In a 1D network of (1)(infinity){[Fe(CH(3)CN)(4)(pyrazine)](ClO(4))(2)}, the
      presence of four neutral nitrile molecules besides the pyrazine donors in the
      first coordination sphere of iron(II) allows one to achieve a ligand field
      strength appropriate for the "spin-crossover" occurrence.

PMID- 21077597
TI  - Ab initio kinetics of gas phase decomposition reactions.
AB  - The thermal and kinetic aspects of gas phase decomposition reactions can be
      extremely complex due to a large number of parameters, a variety of possible
      intermediates, and an overlap in thermal decomposition traces. The experimental
      determination of the activation energies is particularly difficult when several
      possible reaction pathways coexist in the thermal decomposition. Ab initio
      calculations intended to provide an interpretation of the experiment are often of
      little help if they produce only the activation barriers and ignore the kinetics
      of the decomposition process. To overcome this ambiguity, a theoretical study of
      a complete picture of gas phase thermo-decomposition, including reaction
      energies, activation barriers, and reaction rates, is illustrated with the
      example of the beta-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX)
      molecule by means of quantum-chemical calculations. We study three types of major
      decomposition reactions characteristic of nitramines: the HONO elimination, the
      NONO rearrangement, and the N-NO(2) homolysis. The reaction rates were determined
      using the conventional transition state theory for the HONO and NONO
      decompositions and the variational transition state theory for the N-NO(2)
      homolysis. Our calculations show that the HMX decomposition process is more
      complex than it was previously believed to be and is defined by a combination of
      reactions at any given temperature. At all temperatures, the direct N-NO(2)
      homolysis prevails with the activation barrier at 38.1 kcal/mol. The nitro
      nitrite isomerization and the HONO elimination, with the activation barriers at
      46.3 and 39.4 kcal/mol, respectively, are slow reactions at all temperatures. The
      obtained conclusions provide a consistent interpretation for the reported
      experimental data.

PMID- 21077598
TI  - Vibrational spectra of benzene chromium tricarbonyl and its mesityl analogue: a
      study by neutron spectroscopy.
AB  - We have used high resolution neutron vibrational spectroscopy to study the
      vibrations of the model compound for arene-to-metal bonding, benzene chromium
      tricarbonyl, and its mesityl analogue. It is shown that all previously published
      assignment schemes, based on optical spectroscopy alone, are wrong, and new
      assignments are given in agreement with ab initio calculations.

PMID- 21077599
TI  - Mutual solubility of water and structural/positional isomers of N-alkylpyridinium
      based ionic liquids.
AB  - Despite many previous important contributions to the characterization of the
      liquid-liquid phase behavior of ionic liquids (ILs) plus water systems, a gap
      still exists as far as the effect of isomers (of ILs) is concerned. Therefore, in
      this work, a comprehensive study of the liquid-liquid equilibria between water
      and isomeric pyridinium-based ionic liquids has been performed. Atmospheric
      pressure mutual solubilities between water and pyridinium-based ionic liquids
      combined with the common anion bis[(trifluoromethyl)sulfonyl]imide were
      experimentally determined between (288.15 and 318.15) K. The main goal of this
      work is to study the isomeric effects on the pyridinium-based cation, namely, the
      structural and positional isomerism, as well as the alkyl side chain length. To
      the best of our knowledge, the influence of both structural and positional
      isomerism on the liquid-liquid behavior in ionic-liquid-water-containing systems
      is an unexplored field and is here assessed for the first time. Moreover, from
      the experimental solubility data, several infinite dilution molar thermodynamic
      functions of solution, namely, the Gibbs energy, the enthalpy, and the entropy,
      were estimated and discussed. In addition, aiming at gathering a broader picture
      of the underlying thermodynamic solvation phenomenon, molecular dynamics
      simulations were also carried out for the same experimental systems.

PMID- 21077600
TI  - Photophysics and nonlinear absorption of cyclometalated 4,6-diphenyl-2,2'
      bipyridyl platinum(II) complexes with different acetylide ligands.
AB  - The photophysical properties of a series of 4,6-diphenyl-2,2'-bipyridyl
      platinum(II) complexes bearing different sigma-alkynyl ancillary ligands (1a-1k)
      were systematically investigated. All complexes exhibit strong (1)pi,pi*
      absorption bands in the UV region; and broad, structureless charge-transfer
      band(s) in the visible region, which systematically red-shift(s) when the
      electron-donating ability of the para substituent on the phenylacetylide ligand
      increases. All complexes are emissive in solution at room temperature. When
      excited at the charge-transfer absorption band, the complexes exhibit long-lived
      orange emission (lambda(max): 555-601 nm), which is attributed to a triplet metal
      to-ligand charge transfer/intraligand charge transfer emission ((3)MLCT/(3)ILCT).
      Most of these complexes exhibit broad triplet transient difference absorption in
      the visible to the near-IR region, with a lifetime comparable to those measured
      from the decay of the (3)MLCT/(3)ILCT emission. The reverse saturable absorption
      (RSA) of these complexes were demonstrated at 532 nm using nanosecond laser
      pulses. The degree of RSA follows this trend: 1k ~ 1a > 1c > 1f ~ 1i > 1h ~ 1b >
      1e > 1d > 1g, which is mainly determined by the ratio of the triplet excited
      state absorption cross section to that of the ground-state and the triplet
      excited-state quantum yield.

PMID- 21077601
TI  - Computational insight into the static and dynamic polarizabilities of aluminum
      nanoclusters.
AB  - The static and dynamic polarizabilities for the lowest-energy structures of pure
      aluminum clusters up to 31 atoms have been investigated systematically within the
      framework of density functional theory. The size evolution of several electronic
      properties such as ionization potential, electron affinity, the energy gap
      between the highest occupied molecular orbital and lowest unoccupied molecular
      orbital, and chemical hardness have also been discussed for aluminum clusters.
      Our primary focus in this article, however, has been upon the study of
      polarizability of aluminum clusters, although we also looked at the role of other
      electronic properties. From the energetics point of view, the relative stability
      of aluminum clusters at different sizes is studied in terms of the calculated
      second-order difference in the total energy of cluster and fragmentation energy,
      exhibiting that the magic numbers of stabilities are n = 7, 13, and 20. Moreover,
      the minimum polarizability principle is used to characterize the stability of
      aluminum clusters. The results show that polarizabilities and electronic
      properties can reflect obviously the stability of clusters. Electronically, the
      size dependence of ionization potential and electron affinity of clusters is
      determined. On the basis of the Wood and Perdew model these quantities converge
      asymptotically to the value of the bulk aluminum work function.

PMID- 21077602
TI  - Excited-state structure of oligothiophene dendrimers: computational and
      experimental study.
AB  - The nature of one and two-photon absorption enhancement in a series of
      oligothiophene dendrimers, recently proposed for applications in entangled photon
      sensors and solar cells, has been analyzed using both theory (time dependent
      density functional theory calculations) and experiment (fluorescence upconversion
      measurements). The linear absorption spectra exhibit a red shift of the
      absorption maxima and broadening as a function of dendrimer generations. The two
      photon absorption cross sections increase sharply with the number of thiophene
      units in the dendrimer. The cooperative enhancement in absorption two-photon
      cross sections is explained by (i) an increase in the excited-state density for
      larger molecules and (ii) delocalization of the low-lying excited states over
      extended thiophene chains. Fluorescence anisotropy measurements and examination
      of the calculated excited-state properties reveal that this delocalization is
      accompanied by a size-dependent decrease in excited-state symmetries. A
      substantial red shift of the emission maxima for larger dendrimers is explained
      through the vibronic planarization of the longest linear alpha-thiophene chain
      for the emitting excited state. For higher generations, the fluorescence quantum
      yield decreases due to increased nonradiative decay efficiency (e.g., intersystem
      crossing). The detailed information about the dendrimer 3D structure and
      excitations provides guidance for further optimizations of dendritic structures
      for nonlinear optical and opto-electronic applications.

PMID- 21077603
TI  - Zn2+ has a primary hydration sphere of five: IR action spectroscopy and
      theoretical studies of hydrated Zn2+ complexes in the gas phase.
AB  - Complexes of Zn(2+)(H(2)O)(n), where n = 6-12, are examined using infrared
      photodissociation (IRPD) spectroscopy, blackbody infrared radiative dissociation
      (BIRD), and theory. Geometry optimizations and frequency calculations are
      performed at the B3LYP/6-311+G(d,p) level along with single point energy
      calculations for relative energetics at the B3LYP, B3P86, and MP2(full) levels
      with a 6-311+G(2d,2p) basis set. The IRPD spectrum of Zn(2+)(H(2)O)(8) is most
      consistent with the calculated spectrum of the five-coordinate MP2(full) ground
      state (GS) species. Results from larger complexes also point toward a
      coordination number of five, although contributions from six-coordinate species
      cannot be ruled out. For n = 6 and 7, comparisons of the individual IRPD spectra
      with calculated spectra are less conclusive. However, in combination with the
      BIRD and laser photodissociation kinetics as well as a comparison to hydrated
      Cu(2+) and Ca(2+), the presence of five-coordinate species with some contribution
      from six-coordinate species seems likely. Additionally, the BIRD rate constants
      show that Zn(2+)(H(2)O)(6) and Zn(2+)(H(2)O)(7) complexes are less stable than
      Zn(2+)(H(2)O)(8). This trend is consistent with previous work that demonstrates
      the enthalpic favorability of the charge separation process forming singly
      charged hydrated metal hydroxide and protonated water complexes versus loss of a
      water molecule for complexes of n <= 7. Overall, these results are most
      consistent with the lowest-energy structures calculated at the MP2(full) level of
      theory and disagree with those calculated at B3LYP and B3P86 levels.

PMID- 21077604
TI  - The missing piece: sediment records in remote Mountain lakes confirm glaciers
      being secondary sources of persistent organic pollutants.
AB  - After atmospheric deposition and storage in the ice, glaciers are temporary
      reservoirs of persistent organic pollutants (POPs). Recently, the hypothesis that
      melting glaciers represent secondary sources of these pollutants has been
      introduced by investigations of the historical trend of POPs in a dated sediment
      core from the proglacial Alpine Lake Oberaar. Here, the hypothesis is further
      confirmed by the comparison of sediment data gathered from two Alpine lakes with
      a glaciated and a nonglaciated hydrological catchment. The two lakes (Lake
      Engstlen and Lake Stein in the Bernese Alps in Switzerland) are situated only 8
      km apart at similar altitude and in the same meteorological catchment. In the
      nonglacial lake sediment of Lake Engstlen, PCBs and DDT (polychlorinated
      biphenyls and dichlorodiphenyl trichloroethane) levels culminated with the
      historic usage of these chemicals some 30-50 years ago. In the glacial Lake
      Stein, this peak was followed by a reincrease in the 1990s, which goes along with
      the accelerated melting of the adjacent glacier. This study confirms the
      hypothesis of glaciers being a secondary source of these pollutants and is in
      accordance with the earlier findings in Lake Oberaar.

PMID- 21077605
TI  - Oxygen and superoxide-mediated redox kinetics of iron complexed by humic
      substances in coastal seawater.
AB  - Complexes with terrestrially derived humic substances represent one of the most
      reactive pools of dissolved Fe in natural waters. In this work, redox kinetics of
      Fe-humic substance complexes (FeL) in simulated coastal seawater were
      investigated using chemiluminescence techniques with particular attention given
      to interactions with dioxygen (O2) and superoxide (O2*-). Although rate constants
      of FeIIL oxidation by O2 (5.6-52 M-1 . s-1) were 4-5 orders of magnitude less
      than those for O2*- (6.9-23 * 105 M-1 . s-1),O2 is likely to outcompete O2*- for
      FeIIL oxidation in coastal seawaters where steady-state O2*- concentrations are
      generally subnanomolar. Rate constants for FeIIIL reduction by O2*- of 1.8-5.6 *
      104 M-1 . s-1 were also determined. From the balance of FeIIL oxidation rates and
      O2*- -mediated FeIIIL reduction rates, steady-state FeIIL concentrations were
      estimated to be in the subpicomolar to picomolar range, which is generally lower
      than measured in situ Fe(II) concentrations under relevant conditions. This
      suggests that (i) processes other than O2*- -mediated reduction (such as
      photochemical ligand-to-metal charge transfer) may be responsible for Fe(II)
      formation, (ii) the in situ ligands differ significantly from the humic
      substances used in this work, and/ or (iii) the influence of other environmental
      factors such as pH and temperature on Fe redox kinetics may have to be
      considered.

PMID- 21077606
TI  - Magnetic resonance imaging tracking of stem cells in vivo using iron oxide
      nanoparticles as a tool for the advancement of clinical regenerative medicine.

PMID- 21077607
TI  - Cod (Gadus morhua) muscle proteome cataloging using 1D-PAGE protein separation,
      nano-liquid chromatography peptide fractionation, and linear trap quadrupole
      (LTQ) mass spectrometry.
AB  - Because Atlantic cod (Gadus morhua) has high economic value and its protein-rich
      muscle tissue is a food source, an increased understanding of the effects and
      consequences of environmental, nutritional, biological, and industrial factors on
      meat quality is necessary. To gain insight into cod muscle tissue protein
      composition, a large-scale proteomics approach has been used. One-dimensional
      polyacrylamide gel electrophoresis, nanoflow liquid chromatography peptide
      separation, and linear trap quadrupole mass spectrometry were used to identify
      4804 peptides, which retrieved 9113 cod expressed sequence tags (ESTs), which in
      turn were mapped to 446 unique proteins. The same data set identified 3924
      proteins from the zebrafish protein database, which highlights the complementary
      value of the two approaches. The generated data sets will act as a foundation for
      studies related to physiological status assessment of cod under different
      environmental conditions, screening for diseases, and biomarker identification
      for assessment of fish quality during industrial processing and preservation.

PMID- 21077609
TI  - Activation of methane by zinc: gas-phase synthesis, structure, and bonding of
      HZnCH3.
AB  - The methylzinc hydride molecule, HZnCH3, has been observed in the gas phase for
      the first time in the monomeric form using high-resolution spectroscopic
      techniques. The molecule was synthesized by two methods: the reaction of
      dimethylzinc with hydrogen gas and methane in an AC discharge and the reaction of
      zinc vapor produced in a Broida-type oven with methane in a DC discharge. HZnCH3
      was identified on the basis of its pure rotational spectrum, which was recorded
      using millimeter/submillimeter direct-absorption and Fourier transform microwave
      techniques over the frequency ranges 332-516 GHz and 18-41 GHz, respectively.
      Multiple rotational transitions were measured for this molecule in seven isotopic
      variants. K-ladder structure was clearly present in all of the spectra,
      indicating a molecule with C3v symmetry and a (1)A1 ground electronic state.
      Extensive quadrupole hyperfine structure arising from the (67)Zn nucleus was
      observed for the H(67)ZnCH3 species, suggesting covalent bonding to the zinc
      atom. From the multiple isotopic substitutions, a precise structure for HZnCH3
      has been determined. The influence of the axial hydrogen atom slightly distorts
      the methyl group but stabilizes the Zn-C bond. This study suggests that HZnCH3
      can be formed through the oxidative addition of zinc to methane in the gas phase
      under certain conditions. HZnCH3 is the first metal-methane insertion complex to
      be structurally characterized.

PMID- 21077608
TI  - Chemically self-assembled antibody nanorings (CSANs): design and characterization
      of an anti-CD3 IgM biomimetic.
AB  - A number of clever recombinant methodologies have been developed that
      recapitulate the valencies of IgG's (bivalent) and IgA's (tetravalent). Although
      higher synthetic valencies have been achieved by conjugation of either monoclonal
      antibodies or single-chain antibodies to nanoparticles and liposomes, a method
      for the preparation of recombinant antibodies with valencies similar to IgM's
      (decavalent) but considerably less than what is generally found after antibody
      particle conjugation has yet to be devised. Recently, we have developed a
      methodology for the design of bivalent Chemically Self-Assembled Antibody
      Nanorings (CSANs). We now report the crystal structure of the nanoring subunit
      composed of the E. coli DHFR dimer and a methotrexate dimerizer (MTX2-C9)
      containing a visible nine methylene linker and a protocol for the preparation of
      CSANs from this subunit with valencies similar to IgM's, ranging from 8-10 single
      chain antibodies (scFvs). The multivalent CSANs were reversibly assembled from a
      fusion protein dihydrofolate reductase (DHFR)-DHFR-antiCD3 scFv containing a
      single glycine linker between the two DHFR scaffolding proteins. We also
      demonstrate that, similar to the parental bivalent anti-CD3 monoclonal antibody
      (mAB), anti-CD3 CSANs selectively bind to CD3+ leukemia cells and undergo rapid
      internalization through a caveolin-independent pathway that requires cholesterol,
      actin polymerization, and protein tyrosine kinase activation. While treatment
      with the monoclonal antibody leads to T-cell activation and nearly complete loss
      (i.e., 90%) of the surface displayed T-cell receptor (TCR), only 25-30% of the
      TCR down regulate and no significant T-cell proliferation is observed after
      treatment of peripheral blood mononuclear cells (PBMCs) with anti-CD3 CSANs.
      Consistent with the proliferation findings, 15-25% less CD25 (IL-2 receptor) was
      found on the surface of PBMCs treated with either the polyvalent or bivalent anti
      CD3 CSANs, respectively, than on PBMCs treated with the parental mAB. Comparative
      experiments with F(ab')2 derived from the mAB confirm that the activation of the
      T-cells by the mAB is dependent on the Fc domain, and thus interactions of the
      PBMC T-cells with accessory cells, such as macrophages. Taken together, our
      results demonstrate that anti-CD3 CSANs with valencies ranging from 2 to 8 could
      be employed for radionuclide, drug, or potentially oligonucleotide delivery to T
      cells without, as has been observed for other antibody conjugated nanoparticles,
      the deleterious effects of activation observed for mAB. Further the CSAN
      construct may be adapted for the preparation of other multivalent scFvs.

PMID- 21077610
TI  - Polarization of the pyridine ring: highly functionalized piperidines from
      tungsten-pyridine complex.
AB  - The N-acetylpyridinium complex of {TpW(NO)(PMe3)} undergoes regio- and
      stereoselective reactions with a broad range of common organic nucleophiles,
      providing a family of 1,2-dihydropyridine (DHP) complexes of the form
      TpW(NO)(PMe3)(3,4-eta(2)-DHP). The present study explores the elaboration of
      these systems into novel piperidines. The addition of an acid to the DHP
      complexes generates highly asymmetric pi-allyl complexes that in turn react with
      a second nucleophile at either C3 or C5. The subsequent oxidative decomplexation
      of these materials yields several piperidinamides with unconventional
      substitution patterns.

PMID- 21077611
TI  - H.(H2O)n clusters: microsolvation of the hydrogen atom via molecular ab initio
      gradient embedded genetic algorithm (GEGA).
AB  - A new version of the ab initio gradient embedded genetic algorithm (GEGA) program
      for finding the global minima on the potential energy surface (PES) of mixed
      clusters formed by molecules and atoms is reported. The performance of the
      algorithm is demonstrated on the neutral H.(H(2)O)(n) (n = 1-4) clusters, that
      is, a radical H atom solvated in 1-4 water molecules. These clusters are of a
      fundamental interest. The solvated hydrogen atom forms during photochemical
      events in water, or during scavenging of solvated electrons by acids, and
      transiently exists in biological systems and possibly in inclusion complexes in
      the deep ocean and in the ice shield of earth. The processes associated with its
      existence are intriguingly complex, however, and have been the subject of decades
      long debates. Using GEGA, we explicate the apparently extreme structural
      diversity in the H.(H(2)O)(n) (n = 1-4) clusters. All considered clusters have
      four basic structural types: type I, where the H radical is weakly coordinated to
      the oxygen atom of one of the water molecules; type II, where H is weakly
      coordinated to a H atom of one of the water molecules; type III, consisting of
      H(2), the OH radical, and n - 1 H(2)O molecules; and type IV, consisting of H(3)O
      and n - 1 H(2)O. There are myriads of isomers of all four types. The lowest
      energy species of types I and II are the isoenergetic global minima. H.(H(2)O)(n)
      clusters appear to be a challenging case for GEGA because they have many shallow
      minima close in energy some of which are significantly less stable than the
      global minimum. Additionally, the global minima themselves have high structural
      degeneracy, they are only weakly bound, and they are prone to dissociation. GEGA
      performed exceptionally well in finding both the global and the low-energy local
      minima that were subsequently confirmed at higher levels of theory.

PMID- 21077612
TI  - Charged micelle depletion attraction and interfacial colloidal phase behavior.
AB  - Ensemble total internal reflection microscopy (TIRM) is used to directly measure
      the evolution of colloid-surface depletion attraction with increasing sodium
      dodecyl sulfate (SDS) concentration near the critical micelle concentration
      (CMC). Measured potentials are well described by a modified Asakura-Oosawa (AO)
      depletion potential in addition to electrostatic and van der Waals contributions.
      The modified AO potential includes effects of electrostatic interactions between
      micelles and surfaces via effective depletant dimensions in an excluded volume
      term and partitioning in an osmotic pressure term. Directly measured colloid
      surface depletion potentials are used in Monte Carlo (MC) simulations to capture
      video microscopy (VM) measurements of micelle-mediated quasi-two-dimensional
      phase behavior including fluid, crystal, and gel microstructures. Our findings
      provide information to develop more rigorous and analytically simple models of
      depletion attraction in charged micellar systems.

PMID- 21077613
TI  - Sodium caseinate stabilized zein colloidal particles.
AB  - The present work deals with the preparation and stabilization of zein colloidal
      particles using sodium caseinate as electrosteric stabilizer. Colloidal particles
      with well-defined size range (120-150 nm) and negative surface potential (-29 to 
      47 mV) were obtained using a simple antisolvent precipitation method. Due to the
      presence of caseinate, the stabilized colloidal particles showed a shift of
      isoelectric point (IEP) from 6.0 to around pH 5.0 and thus prevent the
      aggregation of zein near its native IEP (pH 6.2). The particles also showed good
      stability to varying ionic strength (15 mM-1.5 M NaCl). Furthermore, stabilized
      particles retained the property of redispersibility after drying. In vitro
      protein hydrolysis study confirmed that the presence of caseinate did not alter
      the digestibility of zein. Such colloidal particles could potentially serve as
      all-natural delivery systems for bioactive molecules in food, pharmaceutical, and
      agricultural formulations. 

PMID- 21077614
TI  - C60 aminofullerene immobilized on silica as a visible-light-activated
      photocatalyst.
AB  - A new strategy is described to immobilize photoactive C(60) aminofullerene on
      silica gel (3-(2-succinic anhydride)propyl functionalized silica), thus enabling
      facile separation of the photocatalyst for recycling and repeated use. An organic
      linker moiety containing an amide group was used to anchor C(60) aminofullerene
      to the functionalized silica support. The linker moiety prevents aqueous C(60)
      aggregation/agglomeration (shown by TEM images), resulting in a remarkable
      enhancement of photochemical (1)O(2) production under visible light irradiation.
      With no loss in efficacy of (1)O(2) production plus insignificant chemical
      modification of the aminoC(60)/silica photocatalyst after multiple cycling, the
      system offers a promising new visible-light-activated photocatalyst. Under
      visible-light irradiation, the aminoC(60)/silica photocatalyst is capable of
      effective and kinetically enhanced oxidation of Ranitidine and Cimetidine
      (pharmaceutical pollutants) and inactivation of MS-2 bacteriophage compared to
      aqueous solutions of the C(60) aminofullerene alone. Thus, this photocatalyst
      could enable water treatment in less developed areas by alleviating dependence on
      major infrastructure, including the need for electricity.

PMID- 21077615
TI  - Dye-sensitized solar cells based on WO3.
AB  - In research on alternative photoanode materials for dye-sensitized solar cells
      (DSCs), there is rarely any report on WO(3), probably due to its acidic surface
      and more positive (vs NHE) conduction band edge position compared to TiO(2) and
      ZnO. For the first time, dye-sensitized solar cells based on porous WO(3)
      nanoparticle films were successfully fabricated with efficiency of up to 0.75%.
      The multicrystalline structure of WO(3) was examined by Raman spectroscopy and X
      ray diffraction analysis. It was found that significant performance enhancement
      can be obtained from treating the WO(3) nanoparticle film with TiCl(4); the
      TiCl(4)-treated WO(3) DSCs were recorded with efficiency reaching 1.46%.

PMID- 21077616
TI  - Growth pattern of Ag(n) (n = 1-8) clusters on the alpha-Al2O3(0001) surface: a
      first principles study.
AB  - We report an extensive first-principles study of the structure and electronic
      properties of Ag(n) (n = 1-8) clusters isolated in gas phase and deposited on the
      alpha-Al(2)O(3) surface. We have used the plane wave based pseudopotential method
      within the framework of density functional theory. The electron ion interaction
      has been described using projector augmented wave (PAW), and the spin-polarized
      GGA scheme was used for the exchange correlation energy. The results reveal that,
      albeit interacting with support alumina, the Ag atoms prefers to remain bonded
      together suggesting an island growth motif is preferred over wetting the surface.
      When compared the equilibrium structures of Ag clusters between free and on
      alumina substrate, a significant difference was observed starting from n = 7
      onward. While Ag(7) forms a three-dimensional (3D) pentagonal bipyramid in the
      isolated gas phase, on alumina support it forms a planar hexagonal structure
      parallel to the surface plane. Moreover, the spin moment of the Ag(7) cluster was
      found to be fully quenched. This has been attributed to higher delocalization of
      electron density as the size of the cluster increases. Furthermore, a comparison
      of chemical bonding analysis through electronic density of state (EDOS) shows
      that the EDOS of the deposited Ag(n) cluster is significantly broader, which has
      been ascribed to the enhanced spd hybridization. On the basis of the energetics,
      it is found that the adsorption energy of Ag clusters on the alpha-Al(2)O(3)
      surface decreases with cluster size.

PMID- 21077617
TI  - Self-assembly of ABC star triblock copolymer thin films confined with a
      preferential surface: a self-consistent mean field theory.
AB  - The microphase separation and morphology of a nearly symmetric A(0.3)B(0.3)C(0.4)
      star triblock copolymer thin film confined between two parallel, homogeneous hard
      walls have been investigated by self-consistent mean field theory (SCMFT) with a
      pseudospectral method. Our simulation experiments reveal that under surface
      confinement, in addition to the typically parallel, perpendicular, and tilted
      cylinders, other phases such as lamellae, perforated lamellae, and complex hybrid
      phases have been found to be stable, which is attributed to block-substrate
      interactions, especially for those hybrid phases in which A and B blocks disperse
      as spheres and alternately arrange as cubic CsCl structures, with a network
      preferred structure of C block. The results show that these hybrid phases are
      also stable within a broad hybrid region (H region) under a suitable film
      thickness and a broad field strength of substrates because their free energies
      are too similar to being distinguished. Phase diagrams have been evaluated by
      purposefully and systematically varying the film thickness and field strength for
      three different cases of Flory-Huggins interaction parameters between species in
      the star polymer. We also compare the phase diagrams for weak and strong
      preferential substrates, each with a couple of opposite quality, and discuss the
      influence of confinement, substrate preference, and the nature of the star
      polymer on the stability of relatively thinner and thick film phases in this
      work.

PMID- 21077618
TI  - Kinetics and mechanism of peroxymonocarbonate formation.
AB  - The kinetics and mechanism of peroxymonocarbonate (HCO(4)(-)) formation in the
      reaction of hydrogen peroxide with bicarbonate have been investigated for the pH
      6-9 range. A double pH jump method was used in which (13)C-labeled bicarbonate
      solutions are first acidified to produce (13)CO(2) and then brought to higher pH
      values by addition of base in the presence of hydrogen peroxide. The time
      evolution of the (13)C NMR spectrum was used to establish the competitive
      formation and subsequent equilibration of bicarbonate and peroxymonocarbonate
      following the second pH jump. Kinetic simulations are consistent with a mechanism
      for the bicarbonate reaction with peroxide in which the initial formation of
      CO(2) via dehydration of bicarbonate is followed by reaction of CO(2) with
      H(2)O(2) (perhydration) and its conjugate base HOO(-) (base-catalyzed
      perhydration). The rate of peroxymonocarbonate formation from bicarbonate
      increases with decreasing pH because of the increased availability of CO(2) as an
      intermediate. The selectivity for formation of HCO(4)(-) relative to the
      hydration product HCO(3)(-) increases with increasing pH as a consequence of the
      HOO(-) pathway and the slower overall equilibration rate, and this pH dependence
      allows estimation of rate constants for the reaction of CO(2) with H(2)O(2) and
      HOO(-) at 25  degrees C (2 * 10(-2) M(-1) s(-1) and 280 M(-1) s(-1),
      respectively). The contributions of the HOO(-) and H(2)O(2) pathways are
      comparable at pH 8. In contrast to the perhydration of many other common
      inorganic and organic acids, the facile nature of the CO(2)/HCO(3)(-) equilibrium
      and relatively high equilibrium availability of the acid anhydride (CO(2)) at
      neutral pH allows for rapid formation of the peroxymonocarbonate ion without
      strong acid catalysis. Formation of peroxymonocarbonate by the reaction of
      HCO(3)(-) with H(2)O(2) is significantly accelerated by carbonic anhydrase and
      the model complex [Zn(II)L(H(2)O)](2+) (L = 1,4,7,10-tetraazacyclododecane).

PMID- 21077619
TI  - Effects of potassium on the supramolecular structure and electronic properties of
      eumelanin thin films.
AB  - The role of potassium in the formation of synthetic eumelanin aggregates is
      investigated by atomic force microscopy and soft-X-ray spectroscopy. Control over
      the thin film granularity is achieved by using K salts, in both drop casting and
      electrodeposition of eumelanin thin films. Further control over orientation is
      made possible by a suitable choice of the substrate: evidence of self-assembly is
      found for thin films deposited on gold. Finally, it is shown that the potassium
      content affects not only the samples morphology, but also the low-lying states in
      the valence band, where a transfer of spectral weight across the HOMO-LUMO gap is
      observed, disclosing possible applications of this multifunctional
      biomacromolecule.

PMID- 21077620
TI  - alpha- and gamma-Hexachlorocyclohexane measurements in the brine fraction of sea
      ice in the Canadian High Arctic using a sump-hole technique.
AB  - We used holes augered partially into first-year sea ice (sumps) to determine
      alpha- and gamma-HCH concentrations in sea-ice brine. The overwintering of the
      CCGS Amundsen in the Canadian western Arctic, as part of the Circumpolar Flaw
      Lead (CFL) System Study, provided the circumstances to allow brine to accumulate
      in sumps sufficiently to test the methodology. We show, for the first time, that
      as much as 50% of total HCHs in seawater can become entrapped within the ice
      crystal matrix. On average, in the winter first-year sea ice HCH brine
      concentrations reached 4.013 +/- 0.307 ng/L and 0.423 +/- 0.013 ng/L for the
      alpha- and gamma-isomer, respectively. In the spring, HCHs decreased gradually
      with time, with increasing brine volume fraction and decreasing brine salinity.
      These decreasing concentrations could be accounted for by both the dilution with
      the ice crystal matrix and under-ice seawater. We propose that the former process
      plays a more significant role considering brine volume fractions calculated in
      this study were below 20%. Levels of HCHs in the brine exceed under-ice water
      concentrations by approximately a factor of 3, a circumstance suggesting that the
      brine ecosystem has been, and continues to be, the most exposed to HCHs.

PMID- 21077621
TI  - Thermal stability of organoclays: effects of duration and atmosphere of
      isothermal heating on iodide sorption.
AB  - Heating periods necessary to destroy iodide sorption capacity of the quaternary
      (alkyl) ammonium and phosphonium modified bentonites were determined using iodide
      sorption batches. For this purpose, prior to the batches the studied organoclays
      were isothermally heated in air in the temperature ranges of 110-180  degrees C
      and 160-300  degrees C, respectively. The temperature dependence of the heating
      periods was found to follow the Arrhenius relationship, which allowed a
      determination of Arrhenius parameters for the reaction leading to the loss of the
      iodide sorption capacity of a bentonite modified by CP(+) (cetylpyridinium),
      BE(+) (benzethonium), CTMA(+) (cetyltrimethylammonium), or TPP(+)
      (tetraphenylphosphonium) surfactant. At 160  degrees C, the thermal stability of
      the iodide sorption capacity of TPP(+)-bentonite is much higher than that of the
      second most stable CTMA(+)-bentonite (80 days vs 5 days). However, the obtained
      Arrhenius parameters predict that CTMA(+)-bentonite becomes the most stable one
      as the heating temperature decreases to 40  degrees C with iodide sorption still
      available for ~12000 years as compared to ~8000 years for TPP(+)-bentonite.
      Heating of the organoclays in a N(2)-atmosphere (<70 ppm O(2)) at 160  degrees C
      revealed that the strong deficit of molecular oxygen in the contacting atmosphere
      resulted in a strong increase of their thermal stability. For CTMA(+)-bentonite,
      this increase is equivalent to the stability increase due to a decrease of the
      heating temperature by ~20  degrees C (from 160  degrees C to ~140  degrees C).
      Accordingly, the iodide sorption capacity of CTMA(+)-bentonite at a heating
      temperature of 40  degrees C is predicted to be retained for ~350,000 years in
      the absence of molecular oxygen.

PMID- 21077622
TI  - Design of structurally rigid trans-diamine-based Tf-amide organocatalysts with a
      dihydroanthracene framework for asymmetric conjugate additions of
      heterosubstituted aldehydes to vinyl sulfones.
AB  - Asymmetric conjugate addition of alpha-heterosubstituted aldehydes such as alpha
      amido and alpha-alkoxy aldehydes to vinyl sulfone was effected under the
      influence of structurally rigid trans-diamine-based Tf-amido organocatalyst (S,S)
      2 with a dihydroanthracene framework to furnish alpha,alpha
      dialkyl(amido)aldehydes and alpha,alpha-dialkyl(alkoxy)aldehydes with high
      enantioselectivity. The chiral efficiency of the structurally unique catalyst
      (S,S)-2 is apparent in comparison with (S,S)-1 and (S,S)-4 with similar
      functionality.

PMID- 21077623
TI  - Microbial electrodialysis cell for simultaneous water desalination and hydrogen
      gas production.
AB  - A new approach to water desalination is to use exoelectrogenic bacteria to
      generate electrical power from the biodegradation of organic matter, moving
      charged ions from a middle chamber between two membranes in a type of microbial
      fuel cell called a microbial desalination cell. Desalination efficiency using
      this approach is limited by the voltage produced by the bacteria. Here we examine
      an alternative strategy based on boosting the voltage produced by the bacteria to
      achieve hydrogen gas evolution from the cathode using a three-chambered system we
      refer to as a microbial electrodialysis cell (MEDC). We examined the use of the
      MEDC process using two different initial NaCl concentrations of 5 g/L and 20 g/L.
      Conductivity in the desalination chamber was reduced by up to 68 +/- 3% in a
      single fed-batch cycle, with electrical energy efficiencies reaching 231 +/- 59%,
      and maximum hydrogen production rates of 0.16 +/- 0.05 m(3) H(2)/m(3) d obtained
      at an applied voltage of 0.55 V. The advantage of this system compared to a
      microbial fuel cell approach is that the potentials between the electrodes can be
      better controlled, and the hydrogen gas that is produced can be used to recover
      energy to make the desalination process self-sustaining with respect to
      electrical power requirements.

PMID- 21077624
TI  - Exploration of bovine milk proteome in colostral and mature whey using an ion
      exchange approach.
AB  - In addition to milk's nutritional role, it contains immunoglobulins (antibodies)
      and immunoregulatory proteins that are active in the digestive tract of newborns.
      However, knowledge of the repertoire of milk proteins remains meager. In this
      work, we report an ion-exchange-based protein fractionation method that allows in
      depth exploration of the whey proteome in bovine milk; 293 unique gene products
      were identified, of which 176 were newly identified in whey. This work also
      demonstrated qualitatively for the first time the consistency, albeit differing
      in protein levels, in milk proteome between colostrum and mature milk (3 mo. post
      calving). Semiquantitative analysis showed a number of up-regulated proteins in
      colostrum that may provide extra natural defenses for the neonate. Increased
      understanding of the composition and functions of bovine milk proteins and their
      potential health benefits may, in the future, play an important role in
      nutritional and biomedical applications as properly processed cow's milk proteins
      could potentially confer the same bioactivity as their human counterparts.

PMID- 21077625
TI  - Iridium-catalyzed arene ortho-silylation by formal hydroxyl-directed C-H
      activation.
AB  - A strategy for the ortho-silylation of aryl ketone, benzaldehyde, and benzyl
      alcohol derivatives has been developed in which a hydroxyl group formally serves
      as the directing element for Ir-catalyzed arene C-H bond activation. One-pot
      generation of a (hydrido)silyl ether from the carbonyl compound or alcohol is
      followed by dehydrogenative cyclization at 80-100  degrees C in the presence of
      norbornene as a hydrogen acceptor and the combination of 1 mol % [Ir(cod)OMe]2
      and 1,10-phenanthroline as a catalyst to form benzoxasiloles. The synthetic
      utility of the benzoxasilole products is demonstrated by conversion to phenol or
      biaryl derivatives by Tamao-Fleming oxidation or Hiyama cross-coupling. Both of
      these transformations of the C-H silylation products exploit the Si-O bond in the
      system and proceed by activation of the silyl moiety with hydroxide, rather than
      fluoride.

PMID- 21077626
TI  - Fabrication of ordered NiO coated Si nanowire array films as electrodes for a
      high performance lithium ion battery.
AB  - Highly ordered NiO coated Si nanowire array films are fabricated as electrodes
      for a high performance lithium ion battery via depositing Ni on electroless
      etched Si nanowires and subsequently annealing. The structures and morphologies
      of as-prepared films are characterized by X-ray diffraction, scanning electron
      microscopy, and transmission electron microscopy. When the potential window
      versus lithium was controlled, the coated NiO can be selected to be
      electrochemically active to store and release Li+ ions, while highly conductive
      crystalline Si cores function as nothing more than a stable mechanical support
      and an efficient electrical conducting pathway. The hybrid nanowire array films
      exhibit superior cyclic stability and reversible capacity compared to that of NiO
      nanostructured films. Owing to the ease of large-scale fabrication and superior
      electrochemical performance, these hybrid nanowire array films will be promising
      anode materials for high performance lithium-ion batteries.

PMID- 21077627
TI  - Tetraureas versus triureas in sulfate binding.
AB  - By mimicking the scaffolds of oligopyridine-based ligands, triurea and tetraurea
      receptors have been developed for sulfate binding. The triureas (L(1), L(2)) show
      stronger binding of sulfate than tetraureas (L(3), L(4)) in DMSO because of their
      better conformational complementarity with sulfate, while the tetraureas display
      better "water tolerance" benefiting from the chelate effect and hydrophobic
      effect.

PMID- 21077628
TI  - Computational study of silica-supported transition metal fragments for Kubas-type
      hydrogen storage.
AB  - To verify the role of the Kubas interaction in transition metal grafted
      mesoporous silicas, and to rationalize unusual rising enthalpy trends with
      surface coverage by hydrogen in these systems, computational studies have been
      performed. Thus, the interaction of H2 with the titanium centers in molecular
      models for experimentally characterized mesoporous silica-based H2 absorption
      materials has been studied quantum chemically using gradient corrected density
      functional theory. The interaction between the titanium and the H2 molecules is
      found to be of a synergic, Kubas type, and a maximum of four H2 molecules can be
      bound to each titanium, in good agreement with previous experiments. The average
      Ti-H2 interaction energies in molecules incorporating benzyl ancillary ligands
      (models of the experimental systems) increase as the number of bound H2 units
      increases from two to four, in agreement with the experimental observation that
      the H2 adsorption enthalpy increases as the number of adsorbed H2 molecules
      increases. The Ti-H2 interaction is shown to be greater when the titanium is
      bound to ancillary ligands, which are poor pi-acceptors, and when the ancillary
      ligand causes the least steric hindrance to the metal. Extension of the target
      systems to vanadium and chromium shows that, for molecules containing hydride
      ancillary ligands, a good relationship is found between the energies of the
      frontier molecular orbitals of the molecular fragments, which interact with
      incoming H2 molecules, and the strength of the M-H2 interaction. For the benzyl
      systems, both the differences in M-H2 interaction energies and the energy
      differences in frontier orbital energies are smaller than those in the hydrides,
      such that conclusions based on frontier orbital energies are less robust than for
      the hydride systems. Because of the high enthalpies predicted for organometallic
      fragments containing hydride ligands, and the low affinity of Cr(III) for
      hydrogen in this study, these features may not be ideal for a practical hydrogen
      storage system.

PMID- 21077629
TI  - Synthesis and electrografting of dendron anchored OEGylated surfaces and their
      protein adsorption resistance.
AB  - In this study, a series of electrochemically active oligo(ethylene glycol) (OEG)
      linear-dendrons have been synthesized and grafted onto electrode surfaces by
      cyclic voltammetry (CV) to improve protein resistance. Dendronized molecules with
      peripheral carbazole functionality and branching architecture enabled tethering
      of the poly(ethylene glycol) (PEG) or OEG group with a predictable number of
      electrochemical reactive groups affecting OEG distribution and orientation. It is
      possible that ample spacing between the OEG chains affects the intrinsic
      hydration of these layers and thus surface protein resistance. The films were
      characterized by CV, surface plasmon resonance (SPR), static contact angle
      measurements, and atomic force microscopy (AFM). This approach should enable
      improved nonbiofouling properties on biorelevant electrode surfaces (metal or
      metal oxides) by potentiostatic or potentiodynamic electrochemical methods,
      providing an alternative to the self-assembled monolayer (SAM) approach for
      anchoring PEG layers.

PMID- 21077630
TI  - N-(2-pyridylmethyl)imines as azomethine precursors in catalytic asymmetric [3 +
      2] cycloadditions.
AB  - An efficient Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition of N-(2
      pyridylmethyl) imines has been developed. In the presence of a
      Cu(CH(3)CN)(4)PF(6)/bisoxazoline catalyst system, high levels of
      enantioselectivity (up to 97% ee) and moderate to high exo selectivity were
      achieved with a wide variety of substituted dipolarophiles, including maleimides,
      fumarates, fumarodinitrile, enones, and nitroalkenes. The reaction with
      unsymmetrically substituted dipolarophiles is completely regioselective.

PMID- 21077631
TI  - Friedel-Crafts acylation of pyrroles and indoles using 1,5-diazabicyclo[4.3.0]non
      5-ene (DBN) as a nucleophilic catalyst.
AB  - 1,5-Diazabicyclo[4.3.0]non-5-ene (DBN) has been shown to be an effective catalyst
      for the regioselective Friedel-Crafts C-acylation of pyrroles and indoles in high
      yields. A detailed mechanistic study implies that DBN is acting as a nucleophilic
      organocatalyst, with the X-ray crystal structure of a key N-acyl-amidine
      intermediate having been determined for the first time.

PMID- 21077632
TI  - Improved mass spectrometric characterization of protein glycosylation reveals
      unusual glycosylation of maize-derived bovine trypsin.
AB  - Although bottom-up proteomics using tryptic digests is widely used to locate post
      translational modifications (PTM) in proteins, there are cases where the protein
      has several potential modification sites within a tryptic fragment and MS(2)
      strategies fail to pinpoint the location. We report here a method using two
      proteolytic enzymes, trypsin and pepsin, in combination followed by tandem mass
      spectrometric analysis to provide fragments that allow one to locate the
      modification sites. We used this strategy to find a glycosylation site on bovine
      trypsin expressed in maize (TrypZean). Several glycans are present, and all are
      attached to a nonconsensus N-glycosylation site on the protein.

PMID- 21077633
TI  - Mass analysis of biological macromolecules at atmospheric pressure using
      nonresonant femtosecond laser vaporization and electrospray ionization.
AB  - A nonresonant femtosecond laser pulse, with an intensity of 10(13) Wcm(-2),
      vaporizes proteins and biomolecules intact, regardless of molecular structure,
      size or electronic structure for subsequent electrospray ionization and transfer
      into a mass spectrometer. Rapid, direct analysis from dried sample, aqueous
      solution and cellular material is demonstrated at atmospheric pressure using
      laser electrospray mass spectrometry (LEMS). Measurements are presented for
      lysozyme (14.3 kDa), hemoglobin from human blood, ovalbumin (45 kDa) from hen egg
      white and phospholipids from hen egg yolk. Mass analysis of biological material
      is performed without dilution, extraction or sample preparation, other than
      placing the biological material onto the sample plate.

PMID- 21077634
TI  - "One-pot" tandem C-H borylation/1,4-conjugate addition/reduction sequence.
AB  - A microwave-assisted, one-pot, iridium-catalyzed aromatic C-H borylation/rhodium
      catalyzed 1,4-conjugate addition sequence provides a highly robust protocol
      suitable for high-throughput array synthesis. Selective formation of either beta
      aryl-substituted ketones or the corresponding alcohols can be achieved in good
      overall yields by simple variation of the reaction conditions.

PMID- 21077635
TI  - Glycoblotting-assisted O-glycomics: ammonium carbamate allows for highly
      efficient o-glycan release from glycoproteins.
AB  - Glycoblotting, high throughput method for N-glycan enrichment analysis based on
      the specific chemical ligation between aminooxy/hydrazide-polymers/solids and
      reducing N-glycans released from whole serum and cellular glycoproteins, was
      proved to be feasible for selective enrichment analysis of O-glycans of common
      (mucin) glycoproteins. We established a standard protocol of glycoblotting-based
      O-glycomics in combination with nonenzymatic chemical treatment to release
      reducing O-glycans predominantly from various glycoprotein samples. It was
      demonstrated that the nonreductive condition employing a simple ammonium salt,
      ammonium carbamate, made glycoblotting-based enrichment analysis of O-glycans
      possible without significant loss or unfavorable side reactions. A general
      workflow of glycoblotting using a hydrazide bead (BlotGlyco H), on-bead chemical
      manipulations, and subsequent mass spectrometry allowed for rapid O-glycomics of
      human milk osteopontin (OPN) and urinary MUC1 glycoproteins purified from healthy
      donors in a quantitative manner. It was revealed that structures of O-glycans in
      human milk OPN were varied with habitual fucosylation and N-acetyllactosamine
      units. It was also suggested that purified human urinary MUC1 was modified
      preferentially by sialylated O-glycans (94% of total) with 7:3 ratio of core 1 to
      core 2 type O-glycans. Versatility of the present strategy is evident because
      this method was proved to be suited for the enrichment analysis of general
      biological and clinical samples such as human serum and urine, cultured human
      cancer cells, and formalin-fixed paraffin-embedded tissue sections. It is our
      belief that the present protocols would greatly accelerate discovery of disease
      relevant O-glycans as potential biomarkers.

PMID- 21077636
TI  - Asymmetric synthesis of all the known phlegmarine alkaloids.
AB  - The asymmetric synthesis of all four of the known natural phlegmarines and one
      synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3
      (triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used
      twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine
      skeleton. Key reactions include the use of a mixed Grignard reagent for the
      second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex
      dihydropyridone, and a von Braun cyanogen bromide N-demethylation of a late
      intermediate. These syntheses confirmed the absolute stereochemistry of all of
      the known phlegmarines.

PMID- 21077637
TI  - Molecular topology analysis of the differences between drugs, clinical candidate
      compounds, and bioactive molecules.
AB  - A new method to decompose molecules is proposed and used to analyze drugs,
      clinical candidate compounds and bioactive molecules. The method classifies a set
      of molecules into a few well-defined classes based on their molecular framework.
      It is then possible to use these classes to investigate differences between
      drugs, clinical candidates and bioactive molecules. The analysis shows that in
      comparison with clinical candidates and bioactive compounds, drugs have a higher
      fraction of compounds with only one ring system. This conclusion is still valid
      after correcting for lipophilicity (ClogP) and molecular size, as well as any
      potential protein target bias in the data sets. Furthermore the molecular bridge
      part of compounds in the drug set has on average fewer ring systems than
      molecules from the other sets. The ring system complexity (RSC) was also
      investigated and for most topological classes drugs have a lower RSC than the
      clinical candidates and bioactive molecules. Hence, this study highlights
      differences in topology between drugs, clinical candidate compounds and bioactive
      molecules.

PMID- 21077638
TI  - NMR reveals two-step association of Congo Red to amyloid beta in low-molecular
      weight aggregates.
AB  - Aggregation of the Amyloid beta peptide into amyloid fibrils is closely related
      to development of Alzheimer's disease. Many small aromatic compounds have been
      found to act as inhibitors of fibril formation, and have inspired the search for
      new drug candidates. However, the detailed mechanisms of inhibition are largely
      unknown. In this study, we have examined in detail the binding of the fibril
      formation inhibitor Congo Red (CR) to monomeric Abeta(1-40) using a combination
      of 1D, 2D, saturation transfer difference, and diffusion NMR, as well as dynamic
      light scattering experiments. Our results show that CR binds to the fibril
      forming stretches of Abeta(1-40) monomers, and that complex formation occurs in
      two steps: An initial 1:1 CR:Abeta(1-40) complex is formed by a relatively strong
      interaction (K(d) ~ 5 MUM), and a 2:1 complex is formed by binding another CR
      molecule in a subsequent weaker binding step (K(d) ~ 300 MUM). The size of these
      complexes is comparable to that of Abeta(1-40) alone. The existence of two
      different complexes might explain the contradictory reports regarding the
      inhibitory effects of CR on the fibril-formation process.

PMID- 21077640
TI  - Entropy localization in proteins.
AB  - The configurational entropy of a protein is under physiological conditions a
      major contributor to the free energy. Its quantitative characterization is
      therefore an important step toward the understanding of protein function. The
      configurational entropy of the oncoprotein MDM2, whose determination is a
      challenge by experiment alone, is studied here by means of 0.4 MUs molecular
      dynamics computer simulations in both the presence and absence of the p53-peptide
      ligand. By characterizing protein motions in dihedral angle space, it is found
      that the motional amplitudes change considerably upon ligand binding while
      correlations between dihedral angle motions are remarkably well conserved. This
      applies for backbone and side-chain dihedral angle pairs at both short- and long
      range distance to the binding site. As a direct consequence, the change of the
      configurational entropy can be decomposed into a sum of local contributions. This
      significantly facilitates the understanding of the relationship between protein
      dynamics and thermodynamics, which is important, for example, in the context of
      protein-ligand and protein-protein interactions. The findings also have
      implications for the direct derivation of entropy changes from site-specific
      dynamics measurements as afforded by NMR spectroscopy.

PMID- 21077639
TI  - An investigation of the distal histidyl hydrogen bonds in oxyhemoglobin: effects
      of temperature, pH, and inositol hexaphosphate.
AB  - On the basis of X-ray crystal structures and electron paramagnetic resonance
      (EPR) measurements, it has been inferred that the O(2) binding to hemoglobin is
      stabilized by the hydrogen bonds between the oxygen ligands and the distal
      histidines. Our previous study by multinuclear nuclear magnetic resonance (NMR)
      spectroscopy has provided the first direct evidence of such H-bonds in human
      normal adult oxyhemoglobin (HbO(2) A) in solution. Here, the NMR spectra of
      uniformly (15)N-labeled recombinant human Hb A (rHb A) and five mutant rHbs in
      the oxy form have been studied under various experimental conditions of pH and
      temperature and also in the presence of an organic phosphate, inositol
      hexaphosphate (IHP). We have found significant effects of pH and temperature on
      the strength of the H-bond markers, i.e., the cross-peaks for the side chains of
      the two distal histidyl residues, alpha58His and beta63His, which form H-bonds
      with the O(2) ligands. At lower pH and/or higher temperature, the side chains of
      the distal histidines appear to be more mobile, and the exchange with water
      molecules in the distal heme pockets is faster. These changes in the stability of
      the H-bonds with pH and temperature are consistent with the changes in the O(2)
      affinity of Hb as a function of pH and temperature and are clearly illustrated by
      our NMR experiments. Our NMR results have also confirmed that this H-bond in the
      beta-chain is weaker than that in the alpha-chain and is more sensitive to
      changes in pH and temperature. IHP has only a minor effect on these H-bond
      markers compared to the effects of pH and temperature. These H-bonds are
      sensitive to mutations in the distal heme pockets but not affected directly by
      the mutations in the quaternary interfaces, i.e., alpha(1)beta(1) and/or
      alpha(1)beta(2) subunit interface. These findings provide new insights regarding
      the roles of temperature, hydrogen ion, and organic phosphate in modulating the
      structure and function of hemoglobin in solution.

PMID- 21077641
TI  - Investigation of the thermal and photochemical reactions of ozone with 2,3
      dimethyl-2-butene.
AB  - The matrix isolation technique, combined with infrared spectroscopy and twin jet
      codeposition, has been used to characterize intermediates formed during the
      ozonolysis of 2,3-dimethyl-2-butene (DMB). Absorptions of early intermediates in
      the twin jet experiments grew up to 200% upon annealing to 35 K. A number of
      these absorptions have been assigned to the elusive Criegee intermediate (CI) and
      secondary ozonide (SOZ) of DMB, transient species not previously observed for
      this system. Also observed was the primary ozonide (POZ), in agreement with
      earlier studies. The wavelength dependence of the photodestruction of these
      product bands was explored with irradiation from lambda >= 220 to >=580 nm.
      Merged jet (flow reactor) experiments generated "late" stable oxidation products
      of DMB. A recently developed concentric jet method was also utilized to increase
      yields and monitor the concentration of intermediates and products formed at
      different times by varying the length of mixing distance (d = 0 to -11 cm) before
      reaching the cold cell for spectroscopic detection. Identification of
      intermediates formed during the ozonolysis of DMB was further supported by (18)O
      and scrambled (16,18)O isotopic labeling experiments as well as theoretical
      density functional calculations at the B3LYP/6-311++G(d,2p) level.

PMID- 21077642
TI  - Structure and stability of tube and cage Ge60H60.
AB  - A tube Ge(60)H(60) isomer in D(5d) symmetry with fused five-membered rings
      located at the ends of the tube is more stable than the fullerene-like I(h) cage
      isomer at the B3LYP/cc-pVDZ level of theory. Introducing endo Ge-H bonds
      increases the stability of both cage and tube isomers. The most stable tube
      isomer can admit six endo Ge-H bonds. The cage isomer can admit 10-12 endo Ge-H
      bonds (H(10)@Ge(60)H(50) and H(12)@Ge(60)H(48)), and they also represent the most
      stable Ge(60)H(60) isomers. The stability order and structural patterns of
      Ge(60)H(60) are the same as those found for the corresponding Si(60)H(60)
      isomers. Moreover, it is found that the 6-31G(d,p) basis set fails to predict the
      relative energies of the Ge(60)H(60) isomers and the Ge(6)H(6) isomers.

PMID- 21077643
TI  - Major antiparallel and minor parallel beta sheet populations detected in the
      membrane-associated human immunodeficiency virus fusion peptide.
AB  - The HIV gp41 protein catalyzes fusion between viral and host cell membranes, and
      its apolar N-terminal region or "fusion peptide" binds to the host cell membrane
      and plays a key role in fusion. "HFP" is a construct containing the fusion
      peptide sequence, induces membrane vesicle fusion, and is an important fusion
      model system. Earlier solid-state nuclear magnetic resonance (SSNMR) studies
      showed that when HFP is associated with membranes with ~30 mol % cholesterol, the
      first 16 residues have predominant beta strand secondary structure and a fraction
      of the strands form antiparallel beta sheet structure with residue 16->1/1->16 or
      17->1/1->17 registries for adjacent strands. In some contrast, other SSNMR and
      infrared studies have been interpreted to support a large fraction of an
      approximately in-register parallel registry of adjacent strands. However, the
      samples had extensive isotopic labeling, and other structural models were also
      consistent with the data. This SSNMR study uses sparse labeling schemes that
      reduce ambiguity in the determination of the fraction of HFP molecules with
      parallel beta registry. Quantitative analysis of the data shows that the parallel
      fraction is at most 0.15 with a much greater fraction of antiparallel 16->1/1->16
      and 17->1/1->17 registries. These data strongly support a model of HFP-induced
      vesicle fusion caused by antiparallel rather than parallel registries and provide
      insight into the arrangement of gp41 molecules during HIV-host cell fusion. This
      study is an example of quantitative determination of a complex structural
      distribution by SSNMR, including experimentally validated inclusion of natural
      abundance contributions to the SSNMR data.

PMID- 21077644
TI  - Comparative dynamics of leucine methyl groups in FMOC-leucine and in a protein
      hydrophobic core probed by solid-state deuteron nuclear magnetic resonance over 7
      324 K temperature range.
AB  - Quantitative dynamics of methyl groups in 9-fluorenylmethyloxycarbonyl-leucine
      (FMOC-leu) have been analyzed and compared with earlier studies of methyl
      dynamics in chicken villin headpiece subdomain protein (HP36) labeled at L69, a
      key hydrophobic core position. A combination of deuteron solid-state nuclear
      magnetic resonance experiments over the temperature range of 7-324 K and
      computational modeling indicated that while the two compounds show the same modes
      of motions, there are marked differences in the best-fit parameters of these
      motions. One of the main results is that the crossover observed in the dynamics
      of the methyl groups in the HP36 sample at 170 K is absent in FMOC-leu. A second
      crossover at around 95-88 K is present in both samples. The differences in the
      behavior of the two compounds suggest that some of the features of methyl
      dynamics reflect the complexity of the protein hydrophobic core and are not
      determined solely by local interactions.

PMID- 21077645
TI  - A general polymer model of unfolded proteins under folding conditions.
AB  - There is increasing evidence that a polypeptide chain in solvent conditions that
      favor folding may have transient structure and is significantly more compact than
      a fully denatured chain. However, there is no sequence-dependent model to capture
      such interactions. In this work, we present a simple and computationally
      inexpensive model based on a wormlike chain with excluded volume. The probability
      distribution of millions of such chains is reweighted to bias compact
      conformations in which residues of similar hydrophobicity are located near each
      other. This model, which has one adjustable parameter, is fit to measured values
      of intramolecular contact formation, which has been shown to be extremely
      sensitive to various models of intrachain distances. We show that under various
      denaturant concentrations, there is good convergence of the model for several
      different sequences with a wide range of dynamics. We also show that this model
      quantitatively predicts paramagnetic resonance enhancement (PRE) measurements
      with no adjustable parameters. Therefore a simple, probabilistic model that
      accounts for sequence-specific interactions may give a more realistic starting
      point for predictions of protein folding.

PMID- 21077646
TI  - Highly sensitive and selective dynamic light-scattering assay for TNT detection
      using p-ATP attached gold nanoparticle.
AB  - TNT is one of the most commonly used nitro aromatic explosives for landmines of
      military and terrorist activities. As a result, there is an urgent need for rapid
      and reliable methods for the detection of trace amount of TNT for screenings in
      airport, analysis of forensic samples, and environmental analysis. Driven by the
      need to detect trace amounts of TNT from environmental samples, this article
      demonstrates a label-free, highly selective, and ultrasensitive para
      aminothiophenol (p-ATP) modified gold nanoparticle based dynamic light scattering
      (DLS) probe for TNT recognition in 100 pico molar (pM) level from
      ethanol:acetonitile mixture solution. Because of the formation of strong pi-donor
      acceptor interaction between TNT and p-ATP, para-aminothiophenol attached gold
      nanoparticles undergo aggregation in the presence of TNT, which changes the DLS
      intensity tremendously. A detailed mechanism for significant DLS intensity change
      has been discussed. Our experimental results show that TNT can be detected
      quickly and accurately without any dye tagging in 100 pM level with excellent
      discrimination against other nitro compounds.

PMID- 21077647
TI  - DNA-functionalized monolithic hydrogels and gold nanoparticles for colorimetric
      DNA detection.
AB  - Highly sensitive and selective DNA detection plays a central role in many fields
      of research, and various assay platforms have been developed. Compared to
      homogeneous DNA detection, surface-immobilized probes allow washing steps and
      signal amplification to give higher sensitivity. Previously research was focused
      on developing glass or gold-based surfaces for DNA immobilization; we herein
      report hydrogel-immobilized DNA. Specifically, acrydite-modified DNA was
      covalently functionalized to the polyacrylamide hydrogel during gel formation.
      There are several advantages of these DNA-functionalized monolithic hydrogels.
      First, they can be easily handled in a way similar to that in homogeneous assays.
      Second, they have a low optical background where, in combination with DNA
      functionalized gold nanoparticles, even ~0.1 nM target DNA can be visually
      detected. By using the attached gold nanoparticles to catalyze the reduction of
      Ag+, as low as 1 pM target DNA can be detected. The gels can be regenerated by a
      simple thermal treatment, and the regenerated gels perform similarly to freshly
      prepared ones. The amount of gold nanoparticles adsorbed through DNA
      hybridization decreases with increasing gel percentage. Other parameters
      including the DNA concentration, DNA sequence, ionic strength of the solution,
      and temperature have also been systematically characterized in this study.

PMID- 21077648
TI  - New clues for nephrotoxicity induced by ifosfamide: preferential renal uptake via
      the human organic cation transporter 2.
AB  - Anticancer treatment with ifosfamide but not with its structural isomer
      cyclophosphamide is associated with development of renal Fanconi syndrome leading
      to diminished growth in children and bone problems in adults. Since both
      cytotoxics share the same principal metabolites, we investigated whether a
      specific renal uptake of ifosfamide is the basis for this differential effect.
      First we studied the interaction of these cytotoxics using cells transfected with
      organic anion or cation transporters and freshly isolated murine and human
      proximal tubules with appropriate tracers. Next we determined changes in membrane
      voltage in proximal tubular cells to understand their differentiated
      nephrotoxicity. Ifosfamide but not cyclophosphamide was significantly transported
      into cells expressing human organic cation transporter 2 (hOCT2) while both did
      not interact with organic anion transporters. This points toward a specific
      interaction of ifosfamide with hOCT2, which is the main OCT isoform in human
      kidney. In isolated human proximal tubules ifosfamide also interacted with
      organic cation transport. This interaction was also seen in isolated mouse
      proximal tubules; however, it was absent in tubules from OCT-deficient mice,
      illustrating the biological importance of this selective transport. Ifosfamide
      decreased the viability of cells expressing hOCT2, but not that of control cells.
      Coadministration of cimetidine, a known competitive substrate of hOCT2,
      completely prevented this ifosfamide-induced toxicity. Finally, ifosfamide but
      not cyclophosphamide depolarized proximal tubular cells. We propose that the
      nephrotoxicity of ifosfamide is due to its selective uptake by hOCT2 into renal
      proximal tubular cells, and that coadministration of cimetidine may be used to
      prevent ifosfamide-induced nephrotoxicity.

PMID- 21077649
TI  - What is the origin of the prepeak in the X-ray scattering of imidazolium-based
      room-temperature ionic liquids?
AB  - The observation of a first sharp diffraction peak (FSDP) at low frequency in the
      X-ray and neutron scattering spectra of different imidazolium-based room
      temperature ionic liquids (RTILs) (the so-called prepeak) has often been
      experimentally interpreted as indicative of mesoscopic organization leading to
      nanoscale segregation and the formation of domains of different morphologies.
      This interpretation that has permeated the analysis of many recently published
      articles deserves an in depth theoretical analysis. In this article, we use
      several different computational techniques to thoroughly dissect the atomistic
      components giving rise to the low-frequency FSDP as well as other features in the
      structure function (S(q)). By understanding how S(q) changes as imidazolium-based
      ionic systems undergo solid-liquid phase transition, and by artificially
      perturbing the liquid structure in a way that directly couples to the intensity
      of the FSDP, we are able to identify in a rigorous way its geometric origin.
      Similar to the solid phase, the liquid phase is characterized by two typical
      length scales between polar groups. The shorter length scale gives rise to a
      shoulder peak in S(q) at about 0.9 A(-1) whereas the longer one gives rise to the
      prepeak.

PMID- 21077650
TI  - A series of new ternary and quaternary compounds in the Li(I)-Ga(III)-Te(IV)-O
      system.
AB  - Systematic explorations of new compounds in the Li(I)-Ga(III)-Te(IV)-O system led
      to two new isomeric ternary gallium tellurites, namely, alpha-Ga(2)(TeO(3))(3)
      and beta-Ga(2)(TeO(3))(3), and two new quaternary lithium gallium tellurites,
      namely, HLi(2)Ga(3)(TeO(3))(6)(H(2)O)(6) and Li(9)Ga(13)Te(21)O(66). alpha
      Ga(2)(TeO(3))(3) is a noncentrosymmetric structure (I43d) and displays a
      moderately strong second-harmonic-generation response that is comparable with
      that of KDP (KH(2)PO(4)). Its structure features a condensed three-dimensional
      (3D) network alternatively connected by GaO(4) tetrahedra and TeO(3) trigonal
      pyramids via corner sharing. beta-Ga(2)(TeO(3))(3) is centrosymmetric (P6(3)/m)
      and features a 3D open framework composed of Ga(2)O(9) dimers bridged by TeO(3)
      groups with one-dimensional (1D) 12-MR channels along the c axis. Although both
      HLi(2)Ga(3)(TeO(3))(6)(H(2)O)(6) and Li(9)Ga(13)Te(21)O(66) crystallized in the
      same space group R3, they belong to different structure types. The structure of
      HLi(2)Ga(3)(TeO(3))(6)(H(2)O)(6) can be viewed as the 1D tunnels of the 3D
      gallium tellurite being occupied by Li(+) and H(+) ions whereas the structure of
      Li(9)Ga(13)Te(21)O(66) is a complicated 3D framework composed of alternating
      gallium tellurite layers and GaO(6) octahedral layers with Li(+) cations being
      located at the cavities of the structure. Optical diffuse-reflectance spectrum
      measurements indicate that all four compounds are insulators and transparent in
      the range of 300-2500 nm.

PMID- 21077651
TI  - Rhombohedrally distorted gamma-brasses Cr(1-x)Fe(x)Ga.
AB  - A series of rhombohedrally distorted gamma-brass structures containing a mixture
      of magnetically active 3d elements, Cr and Fe, Cr(1-x)Fe(x)Ga, is investigated
      crystallographically. These structures consist of chains of trans-face-sharing Ga
      centered transition metal icosahedra. Neutron powder diffraction specifically on
      Cr(0.5)Fe(0.5)Ga, which could be prepared as a single phase material, gave
      lattice constants (11 K) a = 12.5172(2) A and c = 7.8325(2) A and a refined
      composition of Cr(0.502(6))Fe(0.498)Ga = Cr(6.523)Fe(6.477)Ga(13) and revealed
      partial ordering of Cr and Fe atoms among three crystallographic sites. Magnetic
      susceptibility and magnetization studies of Cr(0.5)Fe(0.5)Ga showed the onset of
      magnetic ordering at ca. 25 K. Theoretical calculations suggested both site
      energy and bond-energy factors influencing the Cr/Fe distribution. Heteroatomic
      interactions significantly affect exchange interactions and create low local
      magnetic moments. Models created to mimic Cr(0.5)Fe(0.5)Ga showed ferromagnetic
      Fe-Fe and antiferromagnetic Cr-Fe interactions, with an overall ferrimagnetic
      ordering.

PMID- 21077652
TI  - Determination of 29Si-1H spin-spin coupling constants in organoalkoxysilanes with
      nontrivial scalar coupling patterns.
AB  - Application of polarization transfer techniques such as DEPT and INEPT in (29)Si
      NMR investigation of bridged silane polymerization requires knowledge of indirect
      (29)Si-(1)H scalar coupling constants in the silane system. However, the fully
      coupled (29)Si NMR spectra of these molecules, specifically those containing
      ethylene bridging groups, are too complicated to measure the coupling constants
      directly by visual inspection. This is because unlike hydrocarbon systems where
      one-bond proton-carbon coupling constants exceed other coupling constants by an
      order of magnitude, in silanes the closest proton-silicon pairs are separated by
      two bonds and all coupling coefficients (both homonuclear and heteronuclear) are
      of similar magnitude. In these systems, theoretical tools are required to
      interpret the spectra of even simple molecules. Here, we determine density
      functional theory estimates of (29)Si-(1)H scalar coupling constants and use
      these along with homonuclear coupling constant estimates to resolve the
      nontrivial nature of these spectra. We also report a Karplus equation consistent
      with the dihedral angle dependence of the three-bond homo- and heteronuclear
      coupling in the ethylene bridge. By thermal averaging of DFT coupling constants,
      a good initial guess of the coupled (29)Si spectral pattern is made, which is
      easily refined by curve fitting to determine estimates of all coupling constants
      in the system.

PMID- 21077653
TI  - Effects of nonadditive interactions on ion solvation at the water/vapor
      interface: a molecular dynamics study.
AB  - The solvation of halide ions at the water/vapor interface is investigated by
      using molecular dynamics simulations with nonpolarizable molecular mechanical
      (MM), polarizable MM, and quantum mechanical (QM)/MM methods. The free energy
      profile of the ion solvation is decomposed into the energy and the entropic
      contributions along the ion displacement from inside to the surface of water. It
      is found that the surface affinity of the ion, relative to the bulk value, is
      determined by a subtle balance between the energetic destabilization and the
      entropic stabilization with the ion displacement. The amount of energetic
      destabilization is found to be reduced when nonadditive interactions are
      included, as in the polarizable MM and QM/MM models. The structure of water
      around the ion at the interface is also largely modified when the higher order
      effects are considered. For example, the induced dipole effect enhances the
      solvation structure around the ion at the interface significantly and thus
      reduces the amount of entropic stabilization at the interface, relative to in the
      bulk. It is found that this induced dipole effect causes the slowing in the ion
      water hydrogen bond dynamics at the interface. On the other hand, the higher
      order induced multipole effects in the QM/MM method suppress both the excessive
      enhancement of the solvation structure and the slowing of the ion-water hydrogen
      bond dynamics at the interface. The present study demonstrates that not only the
      induced dipole moment but also the higher order induced multipole moments, which
      are neglected in standard empirical models, are essential for the correct
      description of the ion solvation at the water/vapor interface.

PMID- 21077654
TI  - Anion-directed self-assembly in coordination networks: architectural control via
      cooperative noncovalent interactions.
AB  - The self-assembly of a new flexible tritopic pyrazine-pyridine ligand (pz-3-py)
      with HgX(2) (X = Cl, Br) was investigated. The results show that coordinated
      chloride and bromide anions play different roles, and two architecturally
      different coordination polymers were obtained with the anions used. Where X = Cl,
      in [Hg(MU(3)-pz-3-py)Cl(2)](n) (1), the 2D network is isolated, while for X = Br,
      in [Hg(MU-pz-3-py)Br(2)](n) (2), a 1D zigzag chain is constructed. Our results
      show that noncovalent interactions such as hydrogen bond, halogen...halogen, and
      halogen...pi interactions, when acting cooperatively, are driving forces for the
      selection of different structures.

PMID- 21077655
TI  - Influence of electrolyte composition on liquid-gated carbon nanotube and graphene
      transistors.
AB  - Field-effect transistors based on single-walled carbon nanotubes (SWNTs) and
      graphene can function as highly sensitive nanoscale (bio)sensors in solution.
      Here, we compare experimentally how SWNT and graphene transistors respond to
      changes in the composition of the aqueous electrolyte in which they are immersed.
      We show that the conductance of SWNTs and graphene is strongly affected by
      changes in the ionic strength, the pH, and the type of ions present, in a manner
      that can be qualitatively different for graphene and SWNT devices. We show that
      this sensitivity to electrolyte composition results from a combination of
      different mechanisms including electrostatic gating, Schottky-barrier
      modifications, and changes in gate capacitance. Interestingly, we find strong
      evidence that the sensor response to changes in electrolyte composition is
      affected by a high density of ionizable groups on both the underlying substrate
      and the carbon surfaces. We present a model based on the (regulated) surface
      charge associated with these ionizable groups that explains the majority of our
      data. Our findings have significant implications for interpreting and optimizing
      sensing experiments with nanocarbon transistors. This is particularly true for
      complex biological samples such as cell extracts, growth media, or bodily fluids,
      for which the complete composition of the solution needs to be considered.

PMID- 21077656
TI  - Group 3 metal complexes of radical-anionic 2,2'-bipyridyl ligands.
AB  - A new method for generating group 3 metal complexes containing radical-anionic
      2,2'-bipyridyl (bipy) ligands is described that relies on hydrogen-atom
      abstraction from dearomatized biheterocyclic complexes. This method does not
      involve electron transfer to neutral 2,2'-bipyridyl or salt metathesis between
      the lithium salt of the 2,2'-bipyridyl radical anion and group 3 metal halides.
      The new metal complexes were characterized by single-crystal X-ray diffraction,
      electron paramagnetic resonance, and absorption spectroscopy. Density functional
      theory (DFT) calculations were used to probe the electronic structure of these
      compounds. All these methods support the radical-anionic character of bipy in all
      bipy compounds presented.

PMID- 21077657
TI  - Multiple silicon-hydrogen bond activations at adjacent rhodium and iridium
      centers.
AB  - The reaction of 1 equiv of primary silanes, SiH(3)R (R = Ph, Mes), with
      [RhIr(CO)(3)(dppm)(2)] yields mono(silylene)-bridged complexes of the type
      [RhIr(H)(2)(CO)(2)(MU-SiHR)(dppm)(2)] (R = Ph or Mes), while for R = Ph the
      addition of 2 equiv yields the bis(silylene)-bridged complexes, [RhIr(CO)(2)(MU
      SiHPh)(2)(dppm)(2)]. The kinetic isomer of this bis(silylene)-bridged product has
      the phenyl substituent axial on one silylene unit and equatorial on the other,
      and in the presence of excess silane this rearranges to the thermodynamically
      preferred "axial-axial" isomer, in which the phenyl substituents on each bridging
      silylene unit are axial and parallel to one another. The reaction of 1 equiv of
      diphenylsilane with [RhIr(CO)(3)(dppm)(2)] produces the mono(silylene)-bridged
      product, [RhIr(H)(2)(CO)(2)(MU-SiPh(2))(dppm)(2)], and the subsequent addition of
      silane in the presence of CO yields the silyl/silylene product
      [RhIr(H)(SiPh(2)H)(CO)(3)(kappa(1)-dppm)(MU-SiPh(2))(dppm)]. The reaction of
      [RhIr(CO)(3)(dppm)(2)] with 2 equiv of SiH(2)Me(2) yields the analogous product
      [RhIr(H)(SiMe(2)H)(CO)(3)(kappa(1)-dppm)(MU-SiMe(2))(dppm)]. Low-temperature NMR
      spectroscopic observation of some key intermediates, such as
      [RhIr(H)(SiH(2)Ph)(CO)(2)(MU-CO)(dppm)(2)], formed during the formation of the
      mono(silylene)-bridged species provides evidence for a mechanism involving
      initial Si-H bond activation at Rh, followed by the subsequent Si-H bond
      activation at Ir. The Si-H bond activation of a second equivalent of silane seems
      to be initiated by dissociation of the Rh-bound end of one diphosphine. The
      reaction of diphenylsilane with the cationic complex
      [RhIr(CH(3))(CO)(2)(dppm)(2)][CF(3)SO(3)] gives rise to a different reactivity
      pattern in which Si-H bond activation is initiated at Ir. In this case, the
      cationic silyl-bridged species, [RhIr(CH(3))(CO)(2)(kappa(1):eta(2)
      SiHPh(2))(dppm)(2)][CF(3)SO(3)], contains an agostic Si-H interaction with Rh. In
      solution, at ambient temperature, this complex converts to two species,
      [RhIr(H)(COCH(3))(CO)(MU-H)(MU-SiPh(2))(dppm)(2)][CF(3)SO(3)] and [RhIr(CO)(2)(MU
      H)(MU-SiPh(2))(dppm)(2)] [CF(3)SO(3)], formed by the competing methyl migration
      to CO and reductive elimination of methane, respectively. In the diphenylsilylene
      dihydride product, a weak interaction between the bridging silicon and the
      terminal Ir-bound hydride is proposed on the basis of NMR evidence.

PMID- 21077658
TI  - Recognition of Hg(2+) using diametrically disubstituted cyclam unit.
AB  - A newly synthesized 1,4,8,11-tetraazacyclotetradecane derivative (L),
      functionalized with a diazo moiety as the reporter functionality, is found to
      bind specifically to Hg(2+) with an associated change in color that could be
      visually detected. With biologically benign beta-CD, it forms an inclusion
      complex (L.2beta-CD), which shows a much higher solubility in water, and this
      helps in developing a more intense color on binding to Hg(2+) in a CH(3)CN-HEPES
      buffer medium. The nontoxic nature of L was checked with the living cells of a
      Gram negative bacterium, Pseudomonas putida . Further, experiments revealed that
      these two reagents could be used as staining agents for the detection of Hg(2+)
      present in this microorganism.

PMID- 21077660
TI  - Supramolecular structures of amyloid-related peptides in an ambient water
      nanofilm.
AB  - An ambient water nanofilm condensed on a solid surface provides a good model
      system to study the self-assembling behaviors of peptides in a confined
      environment. In this paper, the self-assembly of three short amyloid-related
      peptides in a water nanofilm confined on a mica substrate was studied using
      drying microcontact printing (D-MUCP) and atomic force microscopy (AFM). The
      three peptides, which share the same amino acid sequence but have different
      terminal groups, were placed on mica surfaces by D-MUCP. The samples were then
      incubated in a chamber with a controlled temperature and relative humidity (RH)
      in which water nanofilms were generated on the sample surfaces. AFM images
      revealed that the peptides assembled into two kinds of supramolecular structures:
      nanofilaments and nanosheets. The peptides' terminal groups and the thickness of
      the water nanofilms determined the self-assembled supramolecular structures in
      the water nanofilm. Through AFM investigation of the formation and transformation
      of the peptides' supramolecular structures, we conclude that the peptides' self
      assembly process was dominated by weak interactions, such as hydrophobic and
      electrostatic interactions and hydrogen bonding, between the peptide molecules,
      the mica substrate, and the water nanofilm. On the basis of these results, a
      model that describes the peptide arrangement in the confined water nanofilm is
      proposed. This study reveals the complicated interactions of the peptides at an
      interface, which may be a general mechanism in vivo because water confinement
      around biomolecules and membranes is a universal phenomenon.

PMID- 21077659
TI  - Chemoenzymatic syntheses and anti-HIV-1 activity of glucose-nucleoside conjugates
      as prodrugs.
AB  - Phosphodiester linked conjugates of various nucleosides such as d4U, d4T, IdUrd,
      ddI, ddA, virazole, ara-A, and ara-C containing a glucosyl moiety have been
      described. These compounds were designed to act as prodrugs, where the
      corresponding 5'-monophosphates may be generated intracellularly. The synthesis
      of the glycoconjugates was achieved in good yields by condensation of a glucosyl
      phosphoramidite 7 with nucleosides in the presence of an activating agent. It was
      demonstrated that the glucose conjugates improve the water solubility of the
      nucleoside analogues, for example, up to 31-fold for the ara-A conjugate compared
      to that of ara-A alone. The new conjugates were tested for their anti-HIV-1
      activity in human lymphocytes. These derivatives offer a convenient design for
      potential prodrug candidates with the possibility of improving the
      physicochemical properties and therapeutic activity of nucleoside analogues.

PMID- 21077661
TI  - Singlet oxygen imaging in polymeric nanofibers by delayed fluorescence.
AB  - Polymeric nanofiber materials loaded with photosensitizers exhibit significant
      antibacterial activity due to their generation of cytotoxic singlet oxygen
      O(2)((1)Delta(g)). A time-gated fluorescence imaging technique was used to
      monitor the photosensitized processes in polystyrene (PS) and gelatin (GE)
      nanofibers loaded with 0.1 wt % tetraphenylporphyrin (TPP) photosensitizer. The
      fluorescence decay of TPP at the periphery of the PS nanofibers was single
      exponential. Increased fluorescence quenching was observed in the domains with
      higher TPP loading, located in the center of the nanofibers, and added a shorter
      lifetime component to the kinetics. The domains exhibiting singlet oxygen
      activity within the nanofibers were visualized and analyzed by singlet oxygen
      sensitized delayed fluorescence imaging (SODF). Whereas O(2)((1)Delta(g)) was
      produced in PS nanofibers, its production in GE nanofibers was limited. These
      results were confirmed by time-resolved phosphorescence measurements at 1270 nm.

PMID- 21077662
TI  - Phase behavior of binary blends of diblock copolymers.
AB  - The phase behavior of binary blends of a long symmetric AB diblock copolymer and
      a short asymmetric AB diblock copolymer is studied using the self-consistent mean
      field theory. The investigation focuses on blends with different short diblocks
      by constructing phase diagrams over the whole blending compositions and a large
      segregation regime. The influences of the chain length ratio (R) of the long and
      short diblock copolymers on their miscibility and on the stability of various
      ordered structures are explored. The theoretical results reveal that the blends
      have a much more complex phase behavior than each constituent copolymer. With the
      increase of the volume fraction of the short diblocks in the blends, multiple
      transitions from a long-period lamellar phase to phases with nonzero interfacial
      curvatures including cylindrical and spherical phases, and finally to a short
      period lamellar phase or disordered phase, are predicted. In particular,
      consistent with experiments, the theory predicts that the cylindrical phase is
      stabilized over a wide blending compositions region in the strong segregation
      region, even though the two constituent diblock copolymers are both lamella
      forming. When the ratio R is large enough, macrophase separation occurs over a
      wide range of blending compositions in a relatively strong segregation regime.
      Various coexisting phases, including those of lamellar and disorder, lamellar and
      cylindrical, cylindrical and cylindrical, cylindrical and disorder, spherical and
      disorder, and cylindrical and spherical, are predicted. In addition, the density
      profiles of the typical ordered structures are presented in order to understand
      the self-organization of the different copolymer chains.

PMID- 21077663
TI  - Relationship between cation arrangement and photocatalytic activity for Sr-Al-Nb
      O double perovskite.
AB  - The relationship between the photocatalytic activity and the arrangement of metal
      cations was investigated with Sr-Al-Nb-O double perovskite (SAN) synthesized at
      1400  degrees C for various calcination times using a solid state reaction.
      Transmission electron microscopic observation revealed that SAN particles had a
      domain structure of completely B-site ordered (Sr(2)AlNbO(6)) and disordered
      (SrAl(0.5)Nb(0.5)O(3)) phases. The ordered phase fraction was determined using a
      newly proposed mixed-phase model for the Rietveld refinement and a method using
      the relative intensity of the superlattice line of powder X-ray diffraction. It
      turned out that the mass fraction of the ordered phase in SAN calcined at 1400 
      degrees C could be controlled by the calcination time as 33% (10 h), 37% (20 h),
      44% (30 h), and 48% (50 h). Photocatalytic activities of SAN for the evolution of
      H(2) and O(2) respectively from aqueous solutions of methanol and AgF decreased
      with increasing the calcination time, that is, with increasing the fraction of
      the ordered phase. These results suggested that the photocatalytic activity of
      ordered Sr(2)AlNbO(6) should be lower than that of disordered
      SrAl(0.5)Nb(0.5)O(3). This is practically the first report to reveal the
      photocatalytic activity of SAN as well as the effect of cation ordering in oxides
      on the photocatalytic activity.

PMID- 21077664
TI  - Understanding the properties of the coagel and gel phases: a 2H and 13C NMR study
      of amphiphilic ascorbic acid derivatives.
AB  - The coagel and gel phases formed by the d and l diastereoisomers of ascorbyl
      dodecanoate (ASC12) in deuterated water were studied through solid-state NMR
      techniques. In particular, the dynamic properties of water and surfactant chains
      were investigated by (2)H and (13)C NMR static spectra, respectively. Two
      fractions of water with very different dynamics were found in the coagel phases,
      one solidlike and one liquidlike, assigned to water strongly bound to the
      surfactant polar heads and bulk water, respectively. Only one kind of
      "intermediate" water was instead detected in the gel phase suggesting that the
      merging of the two types of water in the interlayers between the surfactant
      lamellae occurs at the coagel-to-gel transition. Moreover, the surfactant chains,
      very rigid in the coagel phase, give rise to fast trans-gauche
      interconformational jumps in the gel phase, where almost isotropic reorientations
      of the whole aggregates also occur. A different dynamic behavior was found for
      the two diastereoisomers in particular for what concerns the surfactant molecules
      in the gel phase and the water molecules in the coagel presumably ascribable to
      different inter- and intramolecular interactions that involve the polar heads.

PMID- 21077665
TI  - Aggregation behavior of sodium lignosulfonate in water solution.
AB  - Lignosulfonate is a type of macromolecular surfactant widely used as interfacial
      additive in various industrial fields and it is produced during chemical pulping
      process. In this paper, we present a new effective method for measurement of the
      critical aggregation concentration (CAC) of sodium lignosulfonate (SL) in water
      solution, with which a value of 0.38 g L(-1) was obtained. Through the
      determination of CAC and observation by DLS, the state and dynamics of the
      formation of the SL micelles were disclosed. The results showed that SL was the
      state of individual molecules when its mass concentration was less than CAC; the
      individual SL molecules started to aggregate above CAC and thus micelles formed
      and grew with increasing SL concentration. The SL solution was quickly frozen and
      the structures of SL molecules or micelles were observed by ESEM, revealing that
      the spherical micelles were the main form of SL in the solution. Based on the
      results, the spherical hollow vesicular structure is proposed as a model of the
      aggregated micelles of SL in the solution.

PMID- 21077666
TI  - Arsenate exposure affects amino acids, mineral nutrient status and antioxidants
      in rice (Oryza sativa L.) genotypes.
AB  - Simulated pot experiments were conducted on four rice (Oryza sativa L.) genotypes
      (Triguna, IR-36, PNR-519, and IET-4786) to examine the effects of As(V) on amino
      acids and mineral nutrient status in grain along with antioxidant response to
      arsenic exposure. Rice genotypes responded differentially to As(V) exposure in
      terms of amino acids and antioxidant profiles. Total amino acid content in grains
      of all rice genotypes was positively correlated with arsenic accumulation. While,
      most of the essential amino acids increased in all cultivars except IR-36,
      glutamic acid and glycine increased in IET-4786 and PNR-519. The level of
      nonprotein thiols (NPTs) and the activities of superoxide dismutase (SOD; EC
      1.15.1.1), glutathione reductase (GR; EC 1.6.4.2) and ascorbate peroxidase (APX;
      EC 1.11.1.11) increased in all rice cultivars except IET-4786. A significant
      genotypic variation was also observed in specific arsenic uptake (SAU; mg kg(
      1)dw), which was in the order of Triguna (134) > IR-36 (71) > PNR-519 (53) > IET
      4786 (29). Further, application of As(V) at lower doses (4 and 8 mg L(-1) As)
      enhanced the accumulation of selenium (Se) and other nutrients (Fe, P, Zn, and
      S), however, higher dose (12 mg L(-1) As) limits the nutrient uptake in rice. In
      conclusion, low As accumulating genotype, IET-4786, which also had significantly
      induced level of essential amino acids, seems suitable for cultivation in
      moderately As contaminated soil and would be safe for human consumption.

PMID- 21077667
TI  - Remediation of waters contaminated with MCPA by the yeasts Lipomyces starkeyi
      entrapped in a sol-gel zirconia matrix.
AB  - A single-stage sol-gel route was set to entrap yeast cells of Lipomyces starkeyi
      in a zirconia (ZrO(2)) matrix, and the remediation ability of the resulting
      catalyst toward a phenoxy acid herbicide, 4-chloro-2-methylphenoxyacetic acid
      (MCPA), was studied. It was found that the experimental procedure allowed a high
      dispersion of the microorganisms into the zirconia gel matrix; the ZrO(2) matrix
      exhibited a significant sorption capacity of the herbicide, and the entrapped
      cells showed a degradative activity toward MCPA. The combination of these effects
      leads to a nearly total removal efficiency (>97%) of the herbicide at 30  degrees
      C within 1 h incubation time from a solution containing a very high concentration
      of MCPA (200 mg L(-1)). On the basis of the experimental evidence, a removal
      mechanism was proposed involving in the first step the sorption of the herbicide
      molecules on the ZrO(2) matrix, followed by the microbial degradation operated by
      the entrapped yeasts, the metabolic activity of which appear enhanced under the
      microenvironmental conditions established within the zirconia matrix. Repeated
      batch tests of sorption/degradation of entrapped Lipomyces showed that the
      removal efficiency retained almost the same value of 97.3% after 3 batch tests,
      with only a subsequent slight decrease, probably due to the progressive
      saturation of the zirconia matrix.

PMID- 21077668
TI  - Modifying Randles circuit for analysis of polyoxometalate layer-by-layer films.
AB  - Multilayer films with anionic phosphomolybidic acid (PMo(12)) clusters have been
      fabricated via the electrostatic layer-by-layer (LbL) method. The charged mass
      transport phenomena of these thin films have been studied using cyclic
      voltammetry (CV) and electrochemical impedance spectroscopy (EIS) with
      [Fe(CN)(6)](3-/4-) and [Ru(NH(3))(6)](3+/2+) as the redox probes. By adding a
      film resistance and a film capacitance to the conventional Randles equivalent
      circuit, we can calculate the diffusion coefficient values that help understand
      the microscopic nature of the thin films. When the negatively charged probe
      [Fe(CN)(6)](3-/4-) was used, lower diffusion coefficients were obtained for
      multilayers deposited from higher ionic strength solutions. This relationship was
      less obvious when the positively charged probe [Ru(NH(3))(6)](3+/2+) was used, in
      which the electrostatic attraction between PMo(12) clusters and the probe ions
      complicates the mass-transfer process. It is believed that the addition of salt
      to dipping solutions increases the tortuosity of the films so the mass transport
      takes longer paths, inducing lower diffusion coefficients. Higher PMo(12) loading
      causes lower diffusion coefficients due to the polyoxometalate clusters blocking
      the paths for charged probe ions.

PMID- 21077669
TI  - Bioavailability of PAHs in aluminum smelter affected sediments: evaluation
      through assessment of pore water concentrations and in vivo bioaccumulation.
AB  - Bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) from coal tar pitch
      polluted sediments was predicted by (1) a generic approach based on organic
      carbon-water partitioning and Gibbs linear free energy relationship (between
      K(OW) and K(OC)), and (2) measurements of freely dissolved concentrations of PAHs
      in the sediment pore water, using passive samplers and solid phase extraction.
      Results from these predictions were compared with those from in vivo
      bioaccumulation experiments using Nereis diversicolor (Polychaeta), Hinia
      reticulata (Gastropoda), and Nuculoma tenuis (Bivalvia). Measured sediment/water
      partition coefficients were higher than predicted by the generic approach.
      Furthermore, predicted biota-to-sediment accumulation factors (BSAFs) derived
      from measured pore water concentrations were more in agreement with the
      bioaccumulation observed for two of the three species. Discrepancies associated
      with the third species (N. tenuis) were likely a result of particles remaining in
      the intestine (as shown by microscopic evaluation). These results indicate the
      importance of conducting site-specific evaluations of pore water concentrations
      and/or bioaccumulation studies by direct measurements to accurately provide a
      basis for risk assessment and remediation plans. The importance of knowledge
      regarding specific characteristics of model organisms is emphasized.

PMID- 21077670
TI  - Selective incorporation of nitrile-based infrared probes into proteins via
      cysteine alkylation.
AB  - The nitrile stretching vibration is increasingly used as a sensitive infrared
      probe of local protein environments. However, site-specific incorporation of a
      nitrile moiety into proteins is difficult. Here we show that various aromatic
      nitriles can be easily incorporated into peptides and proteins via either thiol
      alkylation or arylation reaction.

PMID- 21077671
TI  - A highly selective fluorescent probe for visualization of organic hydroperoxides
      in living cells.
AB  - The transcriptional regulatory protein OhrR is converted into a fluorescent
      bioprobe capable of detecting organic hydroperoxides in living cells with high
      sensitivity and selectivity.

PMID- 21077672
TI  - Molecular level interaction of the human acidic fibroblast growth factor with the
      antiangiogenic agent, inositol hexaphosphate .
AB  - Acidic fibroblast growth factor (FGF1) regulates a wide array of important
      biological phenomena such as angiogenesis, cell differentiation, tumor growth,
      and neurogenesis. Generally, FGFs are known for their strong affinity for the
      glycosaminoglycan heparin, as a prerequisite for recognition of a specific
      tyrosine kinase on the cell surface and are responsible for the cell signal
      transduction cascade. Inositol hexaphosphate (IP6) is a natural antioxidant and
      is known for its antiangiogenic role, in addition to its ability to control tumor
      growth. In the present study, we investigated the interaction of IP6 with the
      acidic fibroblast growth factor (FGF1) using various biophysical techniques
      including isothermal calorimetry, circular dichroism, and multidimensional NMR
      spectroscopy. Herein, we have reported the three-dimensional solution structure
      of the FGF1-IP6 complex. These data show that IP6 binds FGF1 and enhances its
      thermal stability. In addition, we also demonstrate that IP6 acts as an
      antagonist to acidic fibroblast growth factor by inhibiting its receptor binding
      and subsequently decreasing the mitogenic activity. The inhibition likely results
      in the ability of IP6 to antagonize the angiogenic and mitogenic activity of
      FGF1.

PMID- 21077673
TI  - Polymer-caged nanobins for synergistic cisplatin-doxorubicin combination
      chemotherapy.
AB  - Multicomponent chemotherapy has increasingly become a strategy of great
      importance in clinical cancer treatments. However, this type of chemotherapy has
      not been demonstrated in nanoscale delivery vehicles where two cytotoxic agents
      can be packaged together, potentially leading to synergistic drug activities.
      Herein, we present the codelivery of doxorubicin and cisplatin via a single
      polymer-caged nanobin (PCN) and show that copackaging can yield strong synergy in
      the efficacy of these agents. Such a PCN comprises a doxorubicin-encapsulated
      liposomal core protected by a pH-responsive cisplatin prodrug-loaded polymer
      shell with tunable drug ratios and surface charge potentials. This dual-agent Pt
      PCN(DXR) formulation dramatically enhances the overall cytotoxicity of each drug
      against cancer cells at reduced doses and exhibits higher synergy than
      combinations of either the free drugs or separately nano-packaged drugs. These
      results clearly indicate that the polymer-caged nanobin platform can offer new
      means for building synergy into combination chemotherapy regimens.

PMID- 21077674
TI  - Self-cross-linked polymer nanogels: a versatile nanoscopic drug delivery
      platform.
AB  - Nanoscopic vehicles that stably encapsulate drug molecules and release them in
      response to a specific trigger are of great interest due to implications in
      therapeutic applications, especially for cancer therapy. For this purpose, we
      have synthesized highly stable polymeric nanogels, in which the kinetics of guest
      molecule release can be fine-tuned by control over cross-linking density. The
      polymer nanogel precursor is based on a random copolymer that contains
      oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain
      functionalities. By introducing variations into the precursor polymer, such as
      molecular weight and the relative percentages of hydrophilic OEG units and
      hydrophobic PDS functionalities, we have achieved significant control over
      nanogel size. We show that the noncovalently encapsulated guest molecules can be
      released in response to a redox trigger, glutathione (GSH). Stability of dye
      encapsulation inside the nanogels and tunability in the release of guest
      molecules have been demonstrated through in vitro fluorescence resonance energy
      transfer (FRET) experiments. We show in vitro doxorubicin delivery into breast
      cancer cells (MCF-7) with nanogels of different cross-linking density to
      demonstrate that it plays a key role in the stable encapsulation of hydrophobic
      drug molecules and the cell-uptake efficiencies.

PMID- 21077675
TI  - Light-activated regulation of cofilin dynamics using a photocaged hydrogen
      peroxide generator.
AB  - Hydrogen peroxide (H2O2) can exert diverse signaling and stress responses within
      living systems depending on its spatial and temporal dynamics. Here we report a
      new small-molecule probe for producing H2O2 on demand upon photoactivation and
      its application for optical regulation of cofilin-actin rod formation in living
      cells. This chemical method offers many potential opportunities for dissecting
      biological roles for H2O2 as well as remote control of cell behavior via H2O2
      mediated pathways.

PMID- 21077676
TI  - Intermolecular alignment in beta2-microglobulin amyloid fibrils.
AB  - The deposition of amyloid-like fibrils, composed primarily of the 99-residue
      protein beta2-microglobulin (beta2m), is one of the characteristic symptoms of
      dialysis-related amyloidosis. Fibrils formed in vitro at low pH and low salt
      concentration share many properties with the disease related fibrils and have
      been extensively studied by a number of biochemical and biophysical methods.
      These fibrils contain a significant beta-sheet core and have a complex cryoEM
      electron density profile. Here, we investigate the intrasheet arrangement of the
      fibrils by means of (15)N-(13)C MAS NMR correlation spectroscopy. We utilize a
      fibril sample grown from a 50:50 mixture of (15)N,(12)C- and (14)N,(13)C-labeled
      beta2m monomers, the latter prepared using 2-(13)C glycerol as the carbon source.
      Together with the use of ZF-TEDOR mixing, this sample allowed us to observe
      intermolecular (15)N-(13)C backbone-to-backbone contacts with excellent
      resolution and good sensitivity. The results are consistent with a parallel, in
      register arrangement of the protein subunits in the fibrils and suggest that a
      significant structural reorganization occurs from the native to the fibril state.

PMID- 21077678
TI  - Reaction of the butter flavorant diacetyl (2,3-butanedione) with N-alpha
      acetylarginine: a model for epitope formation with pulmonary proteins in the
      etiology of obliterative bronchiolitis.
AB  - The butter flavorant diacetyl (2,3-butanedione) is implicated in causing
      obliterative bronchiolitis in microwave popcorn plant workers. Because diacetyl
      modifies arginine residues, an immunological basis for its toxicity is under
      investigation. Reaction products of diacetyl with N-alpha-acetylarginine (AcArg)
      were determined as a model for hapten formation, with characterization by mass
      spectrometry, NMR, and HPLC with UV detection and radiodetection. Four products
      were identified by LC-MS, each with a positive ion of m/z 303 (diacetyl + AcArg);
      one pair displayed an additional ion at m/z 217 (AcArg), the other pair at m/z
      285 (- H(2)O). Their (1)H-(13)C NMR correlation spectra were consistent with the
      addition of one or two of the guanidine nitrogens to form aminols. Open-chain
      pairs interconverted at pH 2, as did the cyclized, but all four interconverted at
      neutral pH. This is the first structural characterization of the covalent adducts
      between diacetyl and an arginine moiety.

PMID- 21077677
TI  - Polarizabilities of adsorbed and assembled molecules: measuring the conductance
      through buried contacts.
AB  - We have measured the polarizabilities of four families of molecules adsorbed to
      Au{111} surfaces, with structures ranging from fully saturated to fully
      conjugated, including single-molecule switches. Measured polarizabilities
      increase with increasing length and conjugation in the adsorbed molecules and are
      consistent with theoretical calculations. For single-molecule switches, the
      polarizability reflects the difference in substrate-molecule electronic coupling
      in the ON and OFF conductance states. Calculations suggest that the switch
      between the two conductance states is correlated with an oxidation state change
      in a nitro functional group in the switch molecules.

PMID- 21077679
TI  - Fruit fly bioassay to distinguish "sweet" sugar structures.
AB  - Palatable response to dietary sugars plays a significant role in influencing
      metabolic health. New structures are being explored with beneficial health
      properties, although consumer acceptance relies heavily on desirable sensory
      properties. Despite the importance of behavioral responses, the ability to
      elucidate structure-preference relationships of sugars is lacking. A wild
      population of Drosophila melanogaster was used as a model to perform pairwise
      comparisons across structural groups to characterize a fruit fly bioassay for
      assessing sugar preference. Preference was successfully described in structurally
      relevant terms, particularly through the ability to directly test sugars of
      related structures in addition to standard sucrose comparisons. The fruit fly
      bioassay also provided the first report on the relative preference for the beta
      linked sugar alcohol, gentiobiitol. In making reference to well-known human
      preferences, the bioassay also raises opportunities for greater understanding of
      behavioral response to sugar structures in general.

PMID- 21077680
TI  - Qualitative and quantitative detection of agricultural microorganisms expressing
      iturin and mop cyclase in soils.
AB  - The environmental release of genetically engineered microorganisms (GEMs) to
      improve agriculture or remediate environmental hazards has raised concern over
      the fate of the organisms and their engineered genes. To detect the
      microorganisms released into the environment at the molecular level, Bacillus
      subtilis KB producing iturin and Pseudomonas fluorescens MX1 carrying the moc
      (mannityl opine catabolism) region from the Agrobacterium tumefaciens were
      employed as model microorganisms. Using specific fusion primers and the TaqMan
      probes, qualitative and quantitative detections of the model organisms by PCR and
      real-time PCR were conducted employing a small-scale soil-core device and pots
      during the six month period. The data indicate that the model bacteria can be
      easily detected by qualitative and quantitative methods in the test systems
      employed, and they do not give significant impacts on the other bacteria in soils
      on the Southern blotting analysis, although long-term observation may be needed.

PMID- 21077681
TI  - Synthesis, in vitro and in vivo biological evaluation, and comprehensive
      understanding of structure-activity relationships of dipeptidyl boronic acid
      proteasome inhibitors constructed from beta-amino acids.
AB  - An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic
      acid proteasome inhibitors constructed from beta-amino acids is reported. SAR
      analysis revealed that bicyclic groups at the R1 position, 3-F substituents at
      the R2 position, and bulky aliphatic groups at the R3 position were favorable to
      the activities. Enzymatic screening results showed that compound 78, comprising
      all of these features, was the most active inhibitor against the 20S human
      proteasome at less than a 2 nM level, as active as the marketed drug bortezomib.
      Cellular assays confirmed that compound 78 was the most potent against two
      hematologic and some solid tumor cells with IC50 values less than 1 MUM.
      Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a
      longer half-life than bortezomib.

PMID- 21077682
TI  - Enhancement of plant essential oils' aqueous solubility and stability using alpha
      and beta cyclodextrin.
AB  - Sodium benzoate has been shown to produce benzene in combination with ascorbic
      acid. This has led to research for safe alternatives from plant essential oils
      and parabens that have shown some antimicrobial activity, but many of these
      compounds exhibit poor solubility in aqueous solutions. Cyclodextrins can
      increase the solubility of many compounds. This work aimed to investigate the
      solubility of 23 plant essential oils and 4 parabens in water and an apple juice
      medium. Four of these compounds were chosen for their low aqueous solubility to
      determine if complexing the compound with alpha- and beta-cyclodextrin would
      increase solubility. Three of the complexes were dissolved in an acidified
      aqueous solution and then studied in glass and polyethylene terephthalate (PET)
      to determine if storage material would affect the stability. Solubility of the 27
      compounds in distilled water ranged from 1.6 mg/L to 2460.6 mg/L and the
      solubility of 18 of the compounds decreased from 2.5 to 84.7% in apple juice
      medium (pH = 3.4, 12-13  degrees Brix). Complexation with cyclodextrin
      dramatically increased the solubility of the compounds, up to 10-fold. Packaging
      material had no effect on concentration of compounds present over 7 days.
      Cyclodextrins were able to increase solubility of these compounds to more
      suitable concentrations, and may lead to viable natural alternatives to sodium
      benzoate.

PMID- 21077683
TI  - Crystal structures of urate bound form of xanthine oxidoreductase: substrate
      orientation and structure of the key reaction intermediate.
AB  - Two contradictory models have been proposed for the binding mode of the substrate
      xanthine to and its activation mechanism by xanthine oxidoreductase. In an effort
      to distinguish between the two models, we determined the crystal structures of
      the urate complexes of the demolybdo-form of the D428A mutant of rat xanthine
      oxidoreductase at 1.7 A and of the reduced bovine milk enzyme at 2.1 A, the
      latter representing a reaction intermediate. The results clearly indicate the
      catalytically relevant binding mode of the substrate xanthine.

PMID- 21077684
TI  - Neonicotinoid insecticides: highlights of a symposium on strategic molecular
      designs.
AB  - Neonicotinoids are the newest of the five major classes of insecticides (the
      others are chlorinated hydrocarbons, organophosphorus compounds,
      methylcarbamates, and pyrethroids), and they make up approximately one-fourth of
      the world insecticide market. Nithiazine was the lead compound from Shell
      Development Co. in California later optimized by Shinzo Kagabu of Nihon Tokushu
      Noyaku Seizo to increase the potency and photostability, resulting in
      imidacloprid and thiacloprid. These discoveries are the basis for the
      International Award for Research in Agrochemicals of the American Chemical
      Society presented in 2010 to Professor Shinzo Kagabu. Five other neonicotinoids
      were added by others for the current set of seven commercial compounds. This
      symposium considers the progress in discovery and development of novel chemotype
      nicotinic insecticides with enhanced effectiveness, unique biological properties,
      and maximal safety. Chemorational approaches considered include physicochemical
      properties, metabolic activation and detoxification, and chemical and structural
      biology aspects potentially facilitating receptor structure-guided insecticide
      design.

PMID- 21077685
TI  - Interfacial molecular structures of polyelectrolyte brush in contact with dry
      nitrogen, water vapor, liquid water, and aqueous electrolyte solution studied by
      sum frequency generation spectroscopy.
AB  - Interfacial structures of alkylated polyvinylpyridine (Cn-PVP) brushes with
      various side chain lengths (n = 2, 6, 12) in dry nitrogen, water vapor, liquid
      water, and aqueous electrolyte solution were investigated by sum frequency
      generation (SFG) spectroscopy. The SFG spectra of the polymer brushes in the CH
      stretching region in dry nitrogen revealed that the conformational order of the
      side chain depended on the chain length. The conformational order of the polymer
      brush with hexyl, C6, side chain, was very high, and the side chain was almost in
      all-trans conformation with the tilt angle of methyl group being ca. 34 degrees 
      with respect to the surface normal. Significant contribution from CH stretching
      of methylene group was observed in the SFG spectra of the polymer brush with the
      shorter, ethyl, C2, or longer, decyl, C12, side chains. Relative intensity of CH
      stretching of methylene group to that of methyl group, that is, degrees of gauche
      defects, increased significantly upon in contact with water vapor at all the
      brushes, and essentially no CH stretching peaks were observed when the brushes
      were in contact with liquid water, showing almost completely disordered
      conformational structure. These conformation changes were very fast, suggesting
      that the changes were related to the orientation change of the side chains. SFG
      spectra of the brush/water interface in the OH stretching region were dominated
      by OH stretching vibration of ice-like water. The higher was the electrolyte
      concentration, the lower was the OH intensity, reflecting the reduction of the
      double layer thickness in solution of higher electrolyte concentration.

PMID- 21077688
TI  - Bringing order to the world of nanowire devices by phase shift lithography.
AB  - Semiconductor nanowire devices have several properties which match future
      requirements of scaling down the size of electronics. In typical microelectronics
      production, a number of microstructures are aligned precisely on top of each
      other during the fabrication process. In the case of nanowires, this mandatory
      condition is still hard to achieve. A technological breakthrough is needed to
      accurately place nanowires at any specific position and then form devices in mass
      production. In this article, an upscalable process combining conventional
      micromachining with phase shift lithography will be demonstrated as a suitable
      tool for nanowire device technology. Vertical Si and ZnO nanowires are
      demonstrated on very large (several cm(2)) areas. We demonstrate how the nanowire
      positions can be controlled, and the resulting nanowires are used for device
      fabrication. As an example Si/ZnO heterojunction diode arrays are fabricated. The
      electrical characterization of the produced devices has also been performed to
      confirm the functionality of the fabricated diodes.

PMID- 21077687
TI  - Stereospecific cross-coupling of secondary alkyl beta-trifluoroboratoamides.
AB  - The stereospecific cross-coupling of enantioenriched nonbenzylic secondary alkyl
      boron compounds has been achieved. The high selectivity toward product formation
      over an undesired beta-H elimination pathway is achieved via an intramolecular
      coordination of an ancillary carbonyl to the metal center in the
      diorganopalladium intermediate.

PMID- 21077689
TI  - Dynamical discrete/continuum linear response shells theory of solvation:
      convergence test for NH4+ and OH- ions in water solution using DFT and DFTB
      methods.
AB  - A new dynamical discrete/continuum solvation model was tested for NH(4)(+) and
      OH(-) ions in water solvent. The method is similar to continuum solvation models
      in a sense that the linear response approximation is used. However, different
      from pure continuum models, explicit solvent molecules are included in the inner
      shell, which allows adequate treatment of specific solute-solvent interactions
      present in the first solvation shell, the main drawback of continuum models.
      Molecular dynamics calculations coupled with SCC-DFTB method are used to generate
      the configurations of the solute in a box with 64 water molecules, while the
      interaction energies are calculated at the DFT level. We have tested the
      convergence of the method using a variable number of explicit water molecules and
      it was found that even a small number of waters (as low as 14) are able to
      produce converged values. Our results also point out that the Born model, often
      used for long-range correction, is not reliable and our method should be applied
      for more accurate calculations.

PMID- 21077690
TI  - Using small molecules and chemical genetics to interrogate signaling networks.
AB  - The limited clinical success of therapeutics targeting cellular signaling
      processes is due to multiple factors, including off-target effects and complex
      feedback regulation encoded within the signaling network. To understand these
      effects, chemical proteomics and chemical genetics tools have been developed to
      map the direct targets of kinase inhibitors, determine the network-level response
      to inhibitor treatment, and to infer network topology. Here we provide an
      overview of chemical phosphoproteomic and chemical genetic methods, including
      specific examples where these methods have been applied to yield biological
      insight regarding network structure and the system-wide effects of targeted
      therapeutics. The challenges and caveats associated with each method are
      described, along with approaches being used to resolve some of these issues. With
      the broad array of available techniques the next decade should see a rapid
      improvement in our understanding of signaling networks regulation and response to
      targeted perturbations, leading to more efficacious therapeutic strategies.

PMID- 21077686
TI  - Organometallic anticancer compounds.

PMID- 21077691
TI  - Cardiac induction of embryonic stem cells by a small molecule inhibitor of
      Wnt/beta-catenin signaling.
AB  - In vitro differentiation of embryonic stem cells is tightly regulated by the same
      key signaling pathways that control pattern formation during embryogenesis. Small
      molecules that selectively target these developmental pathways, including Wnt,
      and BMP signaling may be valuable for directing differentiation of pluripotent
      stem cells toward many desired tissue types, but to date only few such compounds
      have been shown to promote cardiac differentiation. Here, we show that XAV939, a
      recently discovered small molecule inhibitor of Wnt/beta-catenin signaling, can
      robustly induce cardiomyogenesis in mouse ES cells. Our results suggest that a
      timely administration of XAV939 immediately following the formation of mesoderm
      progenitor cells promotes cardiomyogenic development at the expense of other
      mesoderm derived lineages, including the endothelial, smooth muscle, and
      hematopoietic lineages. Given the critical role that Wnt/beta-catenin signaling
      plays in many aspects of embryogenesis and tissue regeneration, XAV939 is a
      valuable chemical probe to dissect in vitro differentiation of stem cells and to
      explore their regenerative potential in a variety of contexts.

PMID- 21077693
TI  - Preparation of anisotropic silica nanoparticles via controlled assembly of
      presynthesized spherical seeds.
AB  - A facile solution process for the preparation of anisotropic silica nanoparticles
      (ASNPs) is presented. ASNPs are prepared via controlled self-assembly of
      spherical silica seeds (22 nm) in alcohol-water mixed media, followed by their in
      situ fixation and overgrowth with tetraethoxysilane (TEOS). Ethanol and L
      arginine (Arg) are used to modify the dielectric constant and ionic strength of
      the reaction media, by which seed assembly is controlled through the adjustment
      of electrostatic interaction. Ethanol and Arg also serve as a cosolvent and a
      catalyst for hydrolysis and condensation of TEOS, respectively, which enables us
      to produce ASNPs in a simple one-pot process. In addition to ASNPs with wormlike
      structures, different kinds of NPs (bimodal spherical NPs, monodisperse spherical
      NPs, and spherical aggregates) have also been obtained by changing the
      concentrations of ethanol and Arg. The length, thickness, or both of ASNPs are
      controlled systematically by varying the concentrations of Arg, seed NPs, and
      TEOS. Other alcoholic cosolvents, such as methanol, 1-propanol, 2-propanol, and t
      butanol, are also effective to give ASNPs when the dielectric constant of the
      alcohol-water mixed media is properly adjusted, showing the versatility of the
      present method.

PMID- 21077694
TI  - Infrared spectroscopic investigation of two isomers of the weakly bound complex
      OCS-(CO2)2.
AB  - Vibration-rotation spectra of the OCS-(CO(2))(2) van der Waals complex were
      studied by means of direct infrared absorption spectroscopy. Complexes were
      generated in a supersonic slit-jet apparatus, and the expansion gas was probed
      using a rapid-scan tunable diode laser. Infrared bands were observed for two
      different isomeric forms of the complex. A relatively strong band centered at
      2058.799 cm(-1) was assigned to the most stable isomer, which has a barrel-shaped
      geometry and is already known from microwave spectroscopy. A weaker infrared band
      centered at 2050.702 cm(-1) was assigned to a new isomeric form, observed here
      for the first time, which was expected on the basis of ab initio calculations.
      Infrared bands for seven isotopomers were recorded in an attempt to quantify the
      structure of the new isomer. Because it has no symmetry elements, nine parameters
      are needed to fully define the geometry. It was possible to determine six of
      these which define the relative position of the OCS monomer with respect to the
      CO(2) dimer fragment in the complex while the remaining three were fixed at their
      ab initio values. Similarities and differences between the faces of the two
      isomers of OCS-(CO(2))(2) and the associated dimers are discussed.

PMID- 21077692
TI  - Identification of direct protein targets of small molecules.
AB  - Small-molecule target identification is a vital and daunting task for the
      chemical biology community as well as for researchers interested in applying the
      power of chemical genetics to impact biology and medicine. To overcome this
      "target ID" bottleneck, new technologies are being developed that analyze protein
      drug interactions, such as drug affinity responsive target stability (DARTS),
      which aims to discover the direct binding targets (and off targets) of small
      molecules on a proteome scale without requiring chemical modification of the
      compound. Here, we review the DARTS method, discuss why it works, and provide new
      perspectives for future development in this area.

PMID- 21077697
TI  - African heat.

PMID- 21077695
TI  - Reaction of lithium diethylamide with an alkyl bromide and alkyl
      benzenesulfonate: origins of alkylation, elimination, and sulfonation.
AB  - A combination of NMR, kinetic, and computational methods are used to examine
      reactions of lithium diethylamide in tetrahydrofuran (THF) with n-dodecyl bromide
      and n-octyl benzenesulfonate. The alkyl bromide undergoes competitive S(N)2
      substitution and E2 elimination in proportions independent of all concentrations
      except for a minor medium effect. Rate studies show that both reactions occur via
      trisolvated-monomer-based transition structures. The alkyl benzenesulfonate
      undergoes competitive S(N)2 substitution (minor) and N-sulfonation (major) with N
      sulfonation promoted at low THF concentrations. The S(N)2 substitution is shown
      to proceed via a disolvated monomer suggested computationally to involve a cyclic
      transition structure. The dominant N-sulfonation follows a disolvated-dimer-based
      transition structure suggested computationally to be a bicyclo[3.1.1] form. The
      differing THF and lithium diethylamide orders for the two reactions explain the
      observed concentration-dependent chemoselectivities.

PMID- 21077698
TI  - Public pharmacovigilance communication: a process calling for evidence-based,
      objective-driven strategies.
AB  - As a contribution to the debate on how best to communicate information on the
      effective and safe use of medicines to patients, healthcare professionals and the
      general public, this article proposes to distinguish between communication and
      transparency purposes, and to test a strategic health communication approach. Any
      organization aiming to improve medicines use could adapt this approach to its
      remits and legal obligations. The approach includes agreeing measurable
      communication objectives through shared problem ownership of all concerned
      parties, evidence-based design and a cyclic process for planning, implementation
      and evaluation of communication as a public health intervention. The evidence
      base, which supplements risk assessment for product- and situation-specific
      communication on safety concerns, would be derived from research into drug
      utilization, medical decision making and risk perception, as well as from the
      participation of patients and healthcare professionals. It is crucial to address
      the practical questions and concerns of medicine users and to find out why
      unfavourable patterns of medicine use persist, in order to develop behaviour
      change models for overcoming these obstacles. For this purpose, appropriate
      models for facilitating the participation of medicine users in the risk
      management process will need to be explored. Such two-way communication would
      inform risk assessment as well as the analysis of risk minimization options,
      allow for agreement upon communication objectives and enable understandable,
      attractive communication materials to be designed. The communication programme
      should use mixed media and repetition of messages for long-term success. This
      would require cooperation within healthcare and medical information systems. An
      evaluation of the effectiveness of the communication should support the
      sustainability of the programme and provide lessons for the future. Given its
      mission, the pharmacovigilance community has the standing and duty to expand its
      scale of action and take the initiative in advancing risk management through a
      scientific approach to improving public communication for the safety of patients.

PMID- 21077699
TI  - Case series in drug safety: a review to determine characteristics and quality.
AB  - Case series and case reports are a cornerstone of drug safety research; however,
      the characteristics of case series published in the literature remain poorly
      examined. A narrative review of case series addressing drug safety, published in
      the literature between 1 January 2003 and 15 July 2009, and identified through a
      PubMed search, was conducted in order to determine their characteristics and
      quality according to the criteria found in the US FDA Pharmacovigilance Guidance
      2005. Of 130 publications that met the search criteria, 11.5% included an
      analytical component and 88.5% were descriptive. The median number of cases
      included in a given case series was 7 (range 2-2195) and the median time period
      for recruitment of the cases was 23 months (range 0.5-96). Overall, 43.1% of case
      series consisted of individual case reports, while 24.6% originated from cohorts
      and 21% from pharmacovigilance databases. Of the case series, 65.1% concerned
      adults (age >=18 years), 11.6% elderly (age >=65 years) and 8.5% youth (<18
      years). Adverse effects involved mainly the skin (18.5%) and the circulatory
      system (13.8%). The main suspected drug classes (Anatomical Therapeutic Chemical
      classification) were nervous system drugs (23.1%) and antineoplastic and
      immunomodulating agents (20.0%). On average, six out of the possible nine US FDA
      Pharmacovigilance Guidance Criteria were fulfilled, with 27% of publications
      fulfilling at least seven criteria. Only 10% reported data on co-morbidity. In
      conclusion, this review highlights the reporting gaps and heterogeneity in
      published case series with respect to size, recruitment period and quality.

PMID- 21077700
TI  - Monitoring adverse events of the vaccination campaign against influenza A (H1N1)
      in the Netherlands.
AB  - BACKGROUND: In November 2009, a vaccination campaign against Influenza A (H1N1)
      was started in the Netherlands. The accelerated registration procedure of the
      vaccines used in this campaign and the use of these vaccines on a large scale
      indicated a need for real-time safety monitoring. OBJECTIVE: To describe the
      processing, analysing and performing of signal detection by the Netherlands
      Pharmacovigilance Centre (Lareb) on reports of adverse events following
      immunization (AEFI) with respect to the two pandemic influenza vaccines,
      Focetria(r) and Pandemrix(r), used in the Netherlands. The secondary aim is to
      provide a summary of the results of the safety monitoring of both vaccines. STUDY
      DESIGN: Description of the process of collecting information and analysis of the
      safety monitoring of the pandemic vaccines during the vaccination campaign
      against H1N1 in the Netherlands. An observational study on adverse events
      following immunization (AEFIs) associated with vaccines used in this campaign was
      conducted. RESULTS: The use of a dedicated web form with predefined AEFIs enabled
      an efficient way of processing and analysing the reports, resulting in a close to
      real-time monitoring of the safety of the vaccines. From 1 November 2009 until 1
      March 2010, 7534 reports concerning one or more AEFIs possibly related to the
      administration of both vaccines were received. 2788 of the reports related to
      Focetria(r) and 4746 of the reports related to Pandemrix(r). The total time
      between receiving the reports and completion was longer for the serious reports
      (average 2.8 days) compared with the non-serious reports (average 0.8 days). The
      profile of the reported adverse events is comparable with the information
      provided in the Summary of Product Characteristics (SPC). Differences in reported
      AEFIs between both vaccines may be caused by bias and confounding due to the
      different populations for which these vaccines have been used. No signals of
      possible batch-related problems were detected for either vaccine. CONCLUSIONS:
      The method applied allowed for real-time monitoring for AEFIs during the mass
      vaccination campaign. The use of web-based forms, preferably with information on
      venue and used batch numbers, enabled an efficient monitoring of possible batch
      related problems. No major safety issues occurred with respect to the type of
      reported AEFIs, or with the batches of either vaccine.

PMID- 21077701
TI  - Fever following immunization with influenza A (H1N1) vaccine in children: a
      survey-based study in the Netherlands.
AB  - BACKGROUND: In November 2009, all children in the Netherlands from 6 months up to
      4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is
      a common adverse event following immunization in children. Pandemrix(r), an
      inactivated, split-virus influenza A (H1N1) vaccine, was used for this age group.
      A clinical study mentioned in the Summary of Product Characteristics of
      Pandemrix(r) found an increased reactogenicity after the second dose in
      comparison with the first dose, particularly in the rate of fever. In the
      Netherlands, this adverse reaction was a point of concern for the parents or
      caregivers of these children. OBJECTIVE: To investigate the course and height of
      fever following the first and second dose of Pandemrix(r) in children aged from 6
      months up to 4 years. The secondary aim was to evaluate the use of an online
      survey during a vaccination campaign. DESIGN: Survey-based descriptive study.
      SETTING: Adverse drug reaction reporting database of the Netherlands
      Pharmacovigilance Centre (Lareb). PARTICIPANTS: Parents or caregivers (n = 839)
      of vaccinated children who reported fever to Lareb following the first
      immunization with Pandemrix(r). Questionnaires were sent by email to parents or
      caregivers of eligible children following the first and second doses of
      Pandremix(r). MAIN OUTCOME MEASURES: Time between vaccination and the occurrence
      of fever, the maximum measured temperature, the occurrence of other adverse
      events after first and second vaccination, the decision to get the second
      vaccination and the social implication of the fever in terms of absence from
      work, nursery or school, and hospitalization. RESULTS: Following the first
      vaccination against Influenza A (H1N1), the height of the fever was between 39.0
      and 40.0 degrees C in 359/639 (56.2%) of the children. In most of these children
      (235/639 [36.8%]), the onset of fever was between 6 and 12 hours following
      vaccination. 450/639 (70.4%) children recovered within 2 days. Of the 539
      responders to the second questionnaire, 380 (70.5%) received the second
      vaccination against Influenza A (H1N1) and 213 (56.1%) of these children
      experienced fever again. The height of the fever was significantly lower (t-test;
      p = 0.001) and the duration was significantly shorter (Pearson's Chi-square; p =
      0.002) in comparison with the first vaccination. The height of the fever after
      the first vaccination was associated with the decision to receive the second
      vaccination (t-test; p = 0.000). In the studied group, 342 (53.5%) parents or
      caregivers needed to stay home from work and 405 (63.4%) children stayed home
      from nursery or school due to fever following the first vaccination. CONCLUSIONS:
      The results of this study can be used in future vaccination campaigns to be able
      to inform people in an evidence-based manner about the risks and benefits of the
      vaccine and to avoid unnecessary concern and negative media attention. This could
      contribute to improved immunization levels. A web-based survey is demonstrated to
      be a useful tool to quickly gather information about a current safety concern and
      consequently inform the public to support an ongoing vaccination campaign.

PMID- 21077702
TI  - An experimental investigation of masking in the US FDA adverse event reporting
      system database.
AB  - BACKGROUND: A phenomenon of 'masking' or 'cloaking' in pharmacovigilance data
      mining has been described, which can potentially cause signals of
      disproportionate reporting (SDRs) to be missed, particularly in pharmaceutical
      company databases. Masking has been predicted theoretically, observed anecdotally
      or studied to a limited extent in both pharmaceutical company and health
      authority databases, but no previous publication systematically assesses its
      occurrence in a large health authority database. OBJECTIVE: To explore the
      nature, extent and possible consequences of masking in the US FDA Adverse Event
      Reporting System (AERS) database by applying various experimental unmasking
      protocols to a set of drugs and events representing realistic pharmacovigilance
      analysis conditions. METHODS: This study employed AERS data from 2001 through
      2005. For a set of 63 Medical Dictionary for Regulatory Activities (MedDRA(r))
      Preferred Terms (PTs), disproportionality analysis was carried out with respect
      to all drugs included in the AERS database, using a previously described urn
      model-based algorithm. We specifically sought masking in which drug removal
      induced an increase in the statistical representation of a drug-event combination
      (DEC) that resulted in the emergence of a new SDR. We performed a series of
      unmasking experiments selecting drugs for removal using rational statistical
      decision rules based on the requirement of a reporting ratio (RR) >1, top-ranked
      statistical unexpectedness (SU) and relatedness as reflected in the WHO
      Anatomical Therapeutic Chemical level 4 (ATC4) grouping. In order to assess the
      possible extent of residual masking we performed two supplemental purely
      empirical analyses on a limited subset of data. This entailed testing every drug
      and drug group to determine which was most influential in uncovering masked SDRs.
      We assessed the strength of external evidence for a causal association for a
      small number of masked SDRs involving a subset of 29 drugs for which level of
      evidence adjudication was available from a previous study. RESULTS: The original
      disproportionality analysis identified 8719 SDRs for the 63 PTs. The SU-based
      unmasking protocols generated variable numbers of masked SDRs ranging from 38 to
      156, representing a 0.43-1.8% increase over the number of baseline SDRs. A
      significant number of baseline SDRs were also lost in the course of our
      experiments. The trend in the number of gained SDRs per report removed was
      inversely related to the number of lost SDRs per protocol. Both the number and
      nature of the reports removed influenced the number of gained SDRs observed. The
      purely empirical protocols unmasked up to ten times as many SDRs. None of the
      masked SDRs had strong external evidence supporting a causal association. Most
      involved associations for which there was no external supporting evidence or were
      in the original product label. For two masked SDRs, there was external evidence
      of a possible causal association. CONCLUSIONS: We documented masking in the FDA
      AERS database. Attempts at unmasking SDRs using practically implementable
      protocols produced only small changes in the output of SDRs in our analysis. This
      is undoubtedly related to the large size and diversity of the database, but the
      complex interdependencies between drugs and events in authentic spontaneous
      reporting system (SRS) databases, and the impact of measures of statistical
      variability that are typically used in real-world disproportionality analysis,
      may be additional factors that constrain the discovery of masked SDRs and which
      may also operate in pharmaceutical company databases. Empirical determination of
      the most influential drugs may uncover significantly more SDRs than protocols
      based on predetermined statistical selection rules but are impractical except
      possibly for evaluating specific events. Routine global exercises to elicit
      masking, especially in large health authority databases are not justified based
      on results available to date. Exercises to elicit unmasking should be driven by
      prior knowledge or obvious data imbalances.

PMID- 21077704
TI  - Stability of a delay equation arising from a juvenile-adult model.
AB  - We consider a delay equation that has been formulated from a juvenile-adult
      population model. We give respective conditions on the vital rates to ensure
      local stability of the positive equilibrium and global stability of the trivial
      equilibrium. We also show that under certain conditions the equation undergoes a
      Hopf bifurcation. We then study global asymptotic stability and present
      bifurcation diagrams for two special cases of the model.

PMID- 21077705
TI  - Using nonlinear model predictive control to find optimal therapeutic strategies
      to modulate inflammation.
AB  - Modulation of the inflammatory response has become a key focal point in the
      treatment of critically ill patients. Much of the computational work in this
      emerging field has been carried out with the goal of unraveling the primary
      drivers, interconnections, and dynamics of systemic inflammation. To translate
      these theoretical efforts into clinical approaches, the proper biological targets
      and specific manipulations must be identified. In this work, we pursue this goal
      by implementing a nonlinear model predictive control (NMPC) algorithm in the
      context of a reduced computational model of the acute inflammatory response to
      severe infection. In our simulations, NMPC successfully identifies patient
      specific therapeutic strategies, based on simulated observations of clinically
      accessible inflammatory mediators, which outperform standardized therapies, even
      when the latter are derived using a general optimization routine. These results
      imply that a combination of computational modeling and NMPC may be of practical
      use in suggesting novel immuno-modulatory strategies for the treatment of
      intensive care patients.

PMID- 21077706
TI  - A model of Varicella-Zoster reactivation.
AB  - Mathematical models have been used to study the dynamic interaction of many
      infectious diseases with the host's immune system. In this paper, we study
      Varicella Zoster Virus, which is responsible for chicken pox (varicella), and
      after a long period of latency, herpes zoster (shingles). After developing the
      model and demonstrating that is exhibits the type of periodic behavior necessary
      for long term latency and reactivation, we examine the implications of the model
      for vaccine booster programs aimed at preventing herpes zoster.

PMID- 21077707
TI  - A model of drug resistance with infection by health care workers.
AB  - Antibiotic resistant organisms (ARO) pose an increasing serious threat in
      hospitals. One of the most life threatening ARO is methicillin-resistant
      staphylococcus aureus (MRSA). In this paper, we introduced a new mathematical
      model which focuses on the evolution of two bacterial strains, drug-resistant and
      non-drug resistant, residing within the population of patients and health care
      workers in a hospital. The model predicts that as soon as drug is administered,
      the average load of the non-resistant bacteria will decrease and eventually
      (after 6 weeks of the model's simulation) reach a very low level. However, the
      average load of drug-resistant bacteria will initially decrease, after treatment,
      but will later bounce back and remain at a high level. This level can be made
      lower if larger amount of drug is given or if the contact between health care
      workers and patients is reduced.

PMID- 21077708
TI  - Minimal state models for ionic channels involved in glucagon secretion.
AB  - Pancreatic alpha cells synthesize and release glucagon. This hormone along with
      insulin, preserves blood glucose levels within a physiological range. During low
      glucose levels, alpha cells exhibit electrical activity related to glucagon
      secretion. In this paper, we introduce minimal state models for those ionic
      channels involved in this electrical activity in mice alpha cells. For estimation
      of model parameters, we use Monte Carlo algorithms to fit steady-state channel
      currents. Then, we simulate dynamic ionic currents following experimental
      protocols. Our aims are 1) To understand the individual ionic channel functioning
      and modulation that could affect glucagon secretion, and 2) To simulate ionic
      currents actually measured in voltage-clamp alpha-cell experiments in mice. Our
      estimations indicate that alpha cells are highly permeable to sodium and
      potassium which mainly manage action potentials. We have also found that our
      estimated N-type calcium channel population and density in alpha cells is in good
      agreement to those reported for L-type calcium channels in beta cells. This
      finding is strongly relevant since both, L-type and N-type calcium channels, play
      a main role in insulin and glucagon secretion, respectively.

PMID- 21077709
TI  - An application of queuing theory to SIS and SEIS epidemic models.
AB  - In this work we consider every individual of a population to be a server whose
      state can be either busy (infected) or idle (susceptible). This server approach
      allows to consider a general distribution for the duration of the infectious
      state, instead of being restricted to exponential distributions. In order to
      achieve this we first derive new approximations to quasistationary distribution
      (QSD) of SIS (Susceptible- Infected- Susceptible) and SEIS (Susceptible- Latent-
      Infected- Susceptible) stochastic epidemic models. We give an expression that
      relates the basic reproductive number, R0 and the server utilization,p.

PMID- 21077710
TI  - A stoichiometrically derived algal growth model and its global analysis.
AB  - Organisms are composed of multiple chemical elements such as carbon, nitrogen,
      and phosphorus. The scarcity of any of these elements can severely restrict
      organismal and population growth. However, many trophic interaction models only
      consider carbon limitation via energy flow. In this paper, we construct an algal
      growth model with the explicit incorporation of light and nutrient availability
      to characterize both carbon and phosphorus limitations. We provide a global
      analysis of this model to illustrate how light and nutrient availability regulate
      algal dynamics.

PMID- 21077711
TI  - Global stability of an epidemic model with delay and general nonlinear incidence.
AB  - An SIR model with distributed delay and a general incidence function is studied.
      Conditions are given under which the system exhibits threshold behaviour: the
      disease-free equilibrium is globally asymptotically stable if R0 is less than 1
      and globally attracting if R0=1; if R0 is larger than 1, then the unique endemic
      equilibrium is globally asymptotically stable. The global stability proofs use a
      Lyapunov functional and do not require uniform persistence to be shown a priori.
      It is shown that the given conditions are satisfied by several common forms of
      the incidence function.

PMID- 21077712
TI  - Time variations in the generation time of an infectious disease: implications for
      sampling to appropriately quantify transmission potential.
AB  - Although the generation time of an infectious disease plays a key role in
      estimating its transmission potential, the impact of the sampling time of
      generation times on the estimation procedure has yet to be clarified. The present
      study defines the period and cohort generation times, both of which are time
      inhomogeneous, as a function of the infection time of secondary and primary
      cases, respectively. By means of analytical and numerical approaches, it is shown
      that the period generation time increases with calendar time, whereas the cohort
      generation time decreases as the incidence increases. The initial growth phase of
      an epidemic of Asian influenza A (H2N2) in the Netherlands in 1957 was
      reanalyzed, and estimates of the basic reproduction number, , from the Lotka
      Euler equation were examined. It was found that the sampling time of generation
      time during the course of the epidemic introduced a time-effect to the estimate
      of . Other historical data of a primary pneumonic plague in Manchuria in 1911
      were also examined to help illustrate the empirical evidence of the period
      generation time. If the serial intervals, which eventually determine the
      generation times, are sampled during the course of an epidemic, direct
      application of the sampled generation-time distribution to the Lotka-Euler
      equation leads to a biased estimate of . An appropriate quantification of the
      transmission potential requires the estimation of the cohort generation time
      during the initial growth phase of an epidemic or adjustment of the time-effect
      (e.g., adjustment of the growth rate of the epidemic during the sampling time) on
      the period generation time. A similar issue also applies to the estimation of the
      effective reproduction number as a function of calendar time. Mathematical
      properties of the generation time distribution in a heterogeneously mixing
      population need to be clarified further.

PMID- 21077713
TI  - A two-sex model for the influence of heavy alcohol consumption on the spread of
      HIV/AIDS.
AB  - The HIV/AIDS epidemic, one of the leading public health problems to have affected
      sub-Sahara Africa, is a multifaceted problem with social, behavioral and
      biological aspects. In the absence of a cure, behavioral change has been
      advocated as an intervention strategy for reversing the epidemic. Empirical
      studies have found heavy alcohol consumption to be a fueling factor for HIV/AIDS
      infection and progression. Previously [20], we formulated and analyzed a one-sex
      deterministic model to capture the dynamics of this deadly interaction. But,
      since alcohol drinking habits, consequent risky sexual practices, alcohol-induced
      immune suppression, etc., can be different for men and women, the primary
      objective of our present paper is to construct a two-sex model aimed at shedding
      light on how both sexes, with varying heavy alcohol consumption trends,
      contribute differently to the HIV/AIDS spread. Based on numerical simulations,
      supported by the UNAIDS epidemiological software SPECTRUM and using the available
      data, our study identifies heavy drinking among men and women to be a major
      driving force for HIV/AIDS in Botswana and sub-Sahara Africa and quantifies its
      hazardous outcomes in terms of increased number of active TB cases and economic
      burden caused by increased need for AntiRetroviral Therapy (ART). Our simulations
      point to the heavy-drinking habits of men as a major reason for the continuing
      disproportionate impact of HIV/AIDS on women in sub-Sahara Africa. Our analysis
      has revealed the possibility of the phenomenon of backward bifurcation. In
      contrast to the result in some HIV vaccination models [52], backward bifurcation
      in our model is not removed by replacing the corresponding standard incidence
      function with a mass action incidence, but is removed by merging the two
      susceptible classes of the same sex into one, i.e., by ignoring acquisition of,
      and ongoing recovery from, heavy-drinking habits among the susceptible
      population.

PMID- 21077714
TI  - An elementary approach to modeling drug resistance in cancer.
AB  - Resistance to drugs has been an ongoing obstacle to a successful treatment of
      many diseases. In this work we consider the problem of drug resistance in cancer,
      focusing on random genetic point mutations. Most previous works on mathematical
      models of such drug resistance have been based on stochastic methods. In
      contrast, our approach is based on an elementary, compartmental system of
      ordinary differential equations. We use our very simple approach to derive
      results on drug resistance that are comparable to those that were previously
      obtained using much more complex mathematical techniques. The simplicity of our
      model allows us to obtain analytic results for resistance to any number of drugs.
      In particular, we show that the amount of resistance generated before the start
      of the treatment, and present at some given time afterward, always depends on the
      turnover rate, no matter how many drugs are simultaneously used in the treatment.

PMID- 21077715
TI  - Rotating antibiotics does not minimize selection for resistance.

PMID- 21077716
TI  - Antibiotic cycling versus mixing: the difficulty of using mathematical models to
      definitively quantify their relative merits.
AB  - We ask the question Which antibiotic deployment protocols select best against
      drug-resistant microbes: mixing or periodic cycling? and demonstrate that the
      statistical distribution of the performances of both sets of protocols, mixing
      and periodic cycling, must have overlapping supports. In other words, it is a
      general, mathematical result that there must be mixing policies that outperform
      cycling policies and vice versa. As a result, we agree with the tenet of
      Bonhoefer et al. [1] that one should not apply the results of [2] to conclude
      that an antibiotic cycling policy that implements cycles of drug restriction and
      prioritisation on an ad-hoc basis can select against drug-resistant microbial
      pathogens in a clinical setting any better than random drug use. However, nor
      should we conclude that a random, per-patient drug-assignment protocol is the de
      facto optimal method for allocating antibiotics to patients in any general sense.

PMID- 21077717
TI  - Differential age effects for implicit and explicit conceptual associative memory.
AB  - Older adults show disproportionate declines in explicit memory for associative
      relative to item information. However, the source of these declines is still
      uncertain. One explanation is a generalized impairment in the processing of
      associative information. A second explanation is a more specialized impairment in
      the strategic, effortful recollection of associative information, leaving less
      effortful forms of associative retrieval preserved. Assessing implicit memory of
      new associations is a way to distinguish between these viewpoints. To date, mixed
      findings have emerged from studies of associative priming in aging. One factor
      that may account for the variability is whether the manipulations inadvertently
      involve strategic, explicit processes. In two experiments we present a novel
      paradigm of conceptual associative priming in which subjects make speeded
      associative judgments about unrelated objects. Using a size classification task,
      Experiment 1 showed equivalent associative priming between young and older
      adults. Experiment 2 generalized the results of Experiment 1 to an inside/outside
      classification task, while replicating the typical age-related impairment in
      associative but not item recognition. Taken together, the findings support the
      viewpoint that older adults can incidentally encode and retrieve new meaningful
      associations despite difficulty with the intentional recollection of the same
      information.

PMID- 21077718
TI  - Generalization of perceptual learning of vocoded speech.
AB  - Recent work demonstrates that learning to understand noise-vocoded (NV) speech
      alters sublexical perceptual processes but is enhanced by the simultaneous
      provision of higher-level, phonological, but not lexical content (Hervais
      Adelman, Davis, Johnsrude, & Carlyon, 2008), consistent with top-down learning
      (Davis, Johnsrude, Hervais-Adelman, Taylor, & McGettigan, 2005; Hervais-Adelman
      et al., 2008). Here, we investigate whether training listeners with specific
      types of NV speech improves intelligibility of vocoded speech with different
      acoustic characteristics. Transfer of perceptual learning would provide evidence
      for abstraction from variable properties of the speech input. In Experiment 1, we
      demonstrate that learning of NV speech in one frequency region generalizes to an
      untrained frequency region. In Experiment 2, we assessed generalization among
      three carrier signals used to create NV speech: noise bands, pulse trains, and
      sine waves. Stimuli created using these three carriers possess the same slow,
      time-varying amplitude information and are equated for naive intelligibility but
      differ in their temporal fine structure. Perceptual learning generalized
      partially, but not completely, among different carrier signals. These results
      delimit the functional and neural locus of perceptual learning of vocoded speech.
      Generalization across frequency regions suggests that learning occurs at a stage
      of processing at which some abstraction from the physical signal has occurred,
      while incomplete transfer across carriers indicates that learning occurs at a
      stage of processing that is sensitive to acoustic features critical for speech
      perception (e.g., noise, periodicity).

PMID- 21077720
TI  - Increased perceptual and conceptual processing difficulty makes the immeasurable
      measurable: negative priming in the absence of probe distractors.
AB  - Negative priming (NP) refers to the finding that people's responses to probe
      targets previously presented as prime distractors are usually slower and more
      error prone than to unrepeated stimuli. In a typical NP experiment, each probe
      target is accompanied by a distractor. It is an accepted, albeit puzzling,
      finding that the NP effect depends on the presence of these probe distractors;
      for, without probe distractors, NP diminishes. This phenomenon causes severe
      problems for the majority of theoretical accounts of NP. In the present study, we
      follow a simple argument, namely that without probe distractors, the difficulty
      of responding to the probe is so low that NP becomes irrelevant. Hence, by
      increasing perceptual processing difficulty, as well as by increasing conceptual
      processing difficulty, significant NP effects with constantly absent probe
      distractors can be reliably observed. In addition, our results also show that NP
      without probe distractors can be found by exclusively manipulating probe display
      processing. This finding furthers our understanding of the processes causing NP.

PMID- 21077719
TI  - Perceptual grouping affects pitch judgments across time and frequency.
AB  - Pitch, the perceptual correlate of fundamental frequency (F0), plays an important
      role in speech, music, and animal vocalizations. Changes in F0 over time help
      define musical melodies and speech prosody, while comparisons of simultaneous F0
      are important for musical harmony, and for segregating competing sound sources.
      This study compared listeners' ability to detect differences in F0 between pairs
      of sequential or simultaneous tones that were filtered into separate,
      nonoverlapping spectral regions. The timbre differences induced by filtering led
      to poor F0 discrimination in the sequential, but not the simultaneous,
      conditions. Temporal overlap of the two tones was not sufficient to produce good
      performance; instead performance appeared to depend on the two tones being
      integrated into the same perceptual object. The results confirm the difficulty of
      comparing the pitches of sequential sounds with different timbres and suggest
      that, for simultaneous sounds, pitch differences may be detected through a
      decrease in perceptual fusion rather than an explicit coding and comparison of
      the underlying F0s.

PMID- 21077721
TI  - Perceiving action-relevant properties of tools through dynamic touch: effects of
      mass distribution, exploration style, and intention.
AB  - At issue in the present series of experiments was the ability to prospectively
      perceive the action-relevant properties of hand-held tools by means of dynamic
      touch. In Experiment 1, participants judged object move-ability. In Experiment 2,
      participants judged how difficult an object would be to hold if held
      horizontally, and in Experiments 3 and 4, participants rated how fast objects
      could be rotated. In each experiment, the first and second moments of mass
      distribution of the objects were systematically varied. Manipulations of wielding
      speed and orientation during restricted exploration revealed perception to be
      constrained by (a) the moments of mass distribution of the hand-tool system, (b)
      the qualities of exploratory wielding movements, and (c) the intention to
      perceive each specific property. The results are considered in the context of the
      ecological theory of dynamic touch. Implications for accounts of the
      informational basis of dynamic touch and for the development of a theory of
      haptically perceiving the affordance properties of tools are discussed.

PMID- 21077722
TI  - Endocrine organs and laser scanning confocal microscopy (LSCM) imaging: vascular
      bed in human spleen.
AB  - OBJECTIVE: This work was aimed to utilize the precise method of laser confocal
      microscopy (LSCM) to depict the image of spatial relationships of the vessel
      network in the tissue structures of the human spleen. METHODS: With the use of
      serial paraffin or vibratome sections of more than 20 MUm thickness infiltrated
      with eosin fluorescence dye the images of arterial and venous walls of different
      calibres, capillaries, and venous sinuses were morphologically revealed. RESULTS:
      Venous sinuses were frequently found to create mutually communicating branches
      and their lining projected into the lumen protruding cells with distinct
      spherically or ovally shaped nuclei, positioned on the brightly fluorescent and
      fragmented lamina basalis. The presence of lymphocytes was distinct in
      periarteriolar lymphoid sheath (PALS) and lymphatic follicles. Lining cells of
      the red pulp veins sporadically contained marked eosinophilic granules.
      CONCLUSION: The method of LSCM allowed: 1. to reveal two-dimensional and sharp
      image of the human spleen structures, 2. to investigate the vertical course of
      venous structures in the tissue, 3. to obtain serial optic sections in z axis to
      their maximum spatial projections. These data will also serve for the creation of
      three-dimensional images of vessel network in the human spleen in the future
      studies.

PMID- 21077723
TI  - Determinant role of gonadal sex hormones in the pathogenesis of urolithiasis in a
      male subject - a document for male predominancy (case study).
AB  - OBJECTIVE: Urolithiasis is a multifactorial disorder influenced by both intrinsic
      and environmental factors. Among the studied factors, male gender with a three
      times higher incidence of urolitlithiasis than female gender is considered as a
      risk factor, but the influence of sex hormones on urinary stone formation remains
      undetermined. Since the association between serum testosterone and urolithiasis
      has yet received only limited attention, the pathogenesis of this male
      predisposition still remains to be elucidated and thus the reason for this male
      predominance remains apparently obscure. METHODS AND RESULTS: In this case study,
      one healthy 38-year old male who participated in a nutrition study developed a
      minor flank pain and has been subjected to ultrasonography which showed 4-5 mm
      calculi located within renal middle calyxes of both kidneys. In addition, the
      results of twice repeated estimation of testosterone, free testosterone,
      estradiol, dihydrotestosterone and sex hormone binding globulin revealed
      hyperandrogenicity as also confirmed by the estimation of those hormones in eight
      males of the same age. CONCLUSION: So far, the association between serum gonadal
      steroids and urolithiasis in males received only limited attention and the
      recommendation for steroid investigation as a basic evaluation to rule out
      treatable systemic causes in urolithiasis patients is warranted. This rare
      finding in man seems to be the first report on this issue presented.

PMID- 21077724
TI  - The effects of levothyroxine substitution on body composition and body mass after
      total thyroidectomy for benign nodular goiter.
AB  - OBJECTIVE: Many patients who have undergone total thyroidectomy complain about
      weight gain and changes in body composition. This prospective study was designed
      to evaluate the effect of thyroxine replacement on body mass index (BMI) and body
      composition following total thyroidectomy for benign multinodular goiter.
      METHODS: Thirty-three consecutive patients were enrolled. The patients of those
      histopathological examination revealed carcinoma (n=5) and who did not present
      for the 6th month follow-up visit (n=6) were excluded. Thyroxine (T4, 100 MUg,
      dose range 50-200 MUg) was started in all patients immediately after the surgery
      and adjusted according to plasma TSH and FT4-FT3 levels in the postoperative 3rd
      week and postoperative 3rd and 6th months respectively to achieve optimal TSH
      within normal reference range (0.5- 4.2 mU/L). Changes in weight, BMI and
      anthropometric measurements were performed preoperatively and in the
      postoperative 3rd and 6th months. RESULTS: The study completed with 22 patients
      (17 female and 5 male, mean: 45.8 years; range: 26-64 years). Fourteen patients
      maintained euthyroid status and eight had subclinical hypothyroidism. There were
      no significant differences between the subclinical hypothyroid and euthyroid
      patients in BMI and the other anthropometric values (p>0.05). In the comparisons
      for age, there were significant changes with regarding weight and BMI. Increases
      in weight were noted as 2.2+/-2.7 kg in age over 45 (n= 14, mean: 52.7 years,
      range: 46-64 years), while 0.1+/-1.3 kg in age under 45 years (mean; 33.8, range:
      26-43 years) and BMI as 0.8+/-1.0 in age over 45 years compared to 0.04+/-0.5 in
      age under 45 years, respectively (p=0.025 and p=0.029, respectively). No
      significant differences were noted in other anthropometric parameters at the end
      of 6th month compared to the baseline value except the triceps skin fold
      (p=0.027). CONCLUSION: Levothyroxine replacement had no effect on their body
      composition; however, age was found to be an important factor for weight gain and
      change in BMI during the midterm follow-up period.

PMID- 21077725
TI  - Possible role of low level laser therapy on bone turnover in ovariectomized rats.
AB  - OBJECTIVE: The aim of this study was to assess the effect of low level laser
      therapy (LLLT) on bone turnover markers in ovariectomized rats. METHODS: Thirty
      adult female albino rats were divided into three groups; Group 1: 10 sham-
      operated control rats; Group 2: 10 bilaterally ovariectomized rats (OVX); Group
      3: 10 OVX rats exposed to LLLT. LLLT was applied on the neck and shaft of femur,
      five times per week for 8 weeks. The dose applied on each point was 1000 Hertz, 5
      Watts for 30 seconds with a total dose of 15 mJoule/cm2. At the end of
      experiment, blood samples were collected and sera were separated for
      determination of serum calcium (Ca), inorganic phosphorus (Pi), osteocalcin and
      alkaline phosphatase (ALP). In addition, a 24 hour urine sample was also
      collected from each rat for the determination of urinary calcium, phosphorous and
      deoxypyridinoline (U-DPD)/creatinine. RESULTS: Significant increase in serum Ca,
      Pi , ALP, osteocalcin and significant decrease in U-DPD/creatinine in LLLT
      exposed group was found as compared to the other two groups. Bone morphological
      findings revealed the increase in calcium deposition and alkaline phosphatase of
      femoral bones in LLLT exposed group as compared to sham-operated and OVX rats.
      The software image analysis showed increased osteoblast numbers, decreased
      osteoclast numbers and increased compact bone thickness in LLLT exposed group.
      Significant positive correlations was obtained between osteoblast numbers and
      serum Ca , Pi, ALP and osteocalcin in LLLT exposed group ,while a significant
      negative correlation was noticed with U-DPD. CONCLUSION: The use of LLLT was
      found effective in enhancing bone formation and decreasing bone resorption in the
      osteoporotic OVX rats. Further studies are necessary to investigate the effect of
      different parameters of LLLT as wave length, duration and also numbers of
      sessions. The potential use of LLLT in postmenopausal women with osteoporosis is
      needed to be verified.

PMID- 21077726
TI  - Transient anorexia, hyper-nociception and cognitive impairment in early adjuvant
      arthritis in rats.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with enhanced pro-inflammatory
      cytokine levels, pain, anorexia, and cognitive changes. The enhanced production
      of cytokines appears before the full manifestation of the disease. So far, any
      experimental data on behavioral effects of early arthritis are lacking. In the
      present series we describe anorexia early changes in, pain hyper-sensitivity and
      altered cognitive behavior during the first four days of adjuvant arthritis in
      rats (AA), when no clinical signs are yet apparent. METHODS: AA was induced to
      male Lewis rats by a single injection of complete Freund's adjuvant (cFA) at the
      base of the tail. Plasma leptin and ghrelin were measured using specific RIA
      methods. Gene expressions for food-regulatory peptides, neuropeptide-Y (NPY) and
      interleukin-1beta (IL-1beta) in the hypothalamic arcuate nuclei (nARC), were
      quantitated by TaqMan real-time PCR. Pain sensation was measured on all four
      limbs and tail by the plantar test. Cognitive functions were tested in the Morris
      water maze (MWM). RESULTS: Levels of orexigenic ghrelin as well as mRNA
      expression of orexigenic NPY in nucleus arcuatus (nRC)re significantly enhanced
      on day 2 of AA only. Reduced body weight and food intake persisted by day 4 with
      the most profound reduction on day 2. The mRNA for anorexigenic IL-1beta in the
      nARC was significantly enhanced on days 2 and 4. Enhanced pain sensitivity was
      observed on day 2, as was the cognitive impairment given by longer time to find
      the hidden platform, longer time spent in thigmotaxis zone, and longer
      trajectory. The less effective strategy used to find the hidden platform was
      observed up to the day 4 of AA. CONCLUSIONS: Early stage of AA brings about
      reduced body weight, food intake, and activation of central orexigenic pathways.
      The observed anorexia could be ascribed to the over-expression of anorexigenic IL
      1beta which dominates over the NPY orexigenic effects. On day 2 of AA higher pain
      sensitivity and cognitive impairment appear. All the observed change tend to
      recover by day 4 of the disease.

PMID- 21077727
TI  - Necrotizing group A streptococcal periorbital infection following adalimumab
      therapy for rheumatoid arthritis.
AB  - OBJECTIVE: (1) To describe a case of necrotizing group A streptococcal
      periorbital infection in a patient receiving treatment with adalimumab (Humira,
      Abbott)-- a fully humanized monoclonal anti-TNF-alpha agent. (2) To identify
      bacterial species responsible for infection with different forms of biological
      therapy. DESIGN: Single interventional case report and literature review. CASE: A
      57-year-old woman developed severe right-sided necrotizing periorbital infection
      whilst receiving treatment with adalimumab for rheumatoid arthritis (RA).
      Cultures grew Lancefield Group A Streptococcus pyogenes. An extensive literature
      search for reports of ocular infections associated with biological therapy was
      conducted. RESULTS: Adalimumab therapy was discontinued and the patient was
      admitted to an intensive care unit. The patient made a complete recovery after
      receiving appropriate antibiotic therapy. Overall Gram-positive cocci are the
      most common infection associated with use of biological therapy. CONCLUSIONS:
      Anti-TNF-alpha agents are powerful immune-modulating drugs with potentially
      serious side effects. This case is the first to link adalimumab to necrotizing
      periorbital infection. Resolved infection does not preclude reintroduction of
      anti-TNF therapy however, careful assessment of the risks versus benefits of
      therapy is required at the individual patient level.

PMID- 21077728
TI  - Obstetrical risk factors for focal intestinal perforation in very low birth
      weight infants.
AB  - OBJECTIVE: Our objective was to determine the obstetrical risk for spontaneous
      focal intestinal perforation (FIP) in very low birth weight (VLBW) infants.
      METHODS: Eight mothers delivered infants who underwent laparotomy for FIP between
      2001 and 2006 in our hospital. A retrospective case-control study of the eight
      case mothers and 32 control mothers was conducted. Clinical findings were
      retrospectively analyzed. RESULTS: There were significant differences in the
      frequency of oligohydramnios (P<0.01) and velamentous cord insertion (P<0.05)
      between cases and controls. The 1-min Apgar score was significantly lower in the
      FIP group than in the control group (P<0.05). Moreover, primigravidity was
      significantly associated with a risk of FIP. CONCLUSIONS: The etiology of FIP may
      be related to changes in the blood circulation, such as fetal hypoxic-ischemic
      episodes or disturbance in the umbilical blood flow, during the antepartum and/or
      intrapartum periods.

PMID- 21077730
TI  - Enumeration of viable CD34(+) cells by flow cytometry in blood, bone marrow and
      cord blood: results of a study of the novel BDTM stem cell enumeration kit.
AB  - BACKGROUND AIMS: Enumeration of CD34(+) cells in leukocyte-rich cell suspensions
      is important for clinical decision-making in stem cell transplantation. Single
      platform flow cytometry assays offer the significant advantages of speed and
      reproducibility, and have therefore become the gold standard in stem cell
      enumeration. The clinical community has recently defined the need for stem cell
      enumeration kits that incorporate viability dyes. The purpose of this study was
      to evaluate a novel assay, BD Biosciences' (BD) stem cell enumeration kit (SCE
      kit(?)), in relation to Beckman Coulter's (BC) commercially available BC Stem
      KitTM. METHODS: Fresh/freeze-thawed samples from leukapheresis, bone marrow and
      cord blood, and fresh normal/mobilized blood, were analyzed with both assays
      (simultaneous detection of side/forward scatter and three fluorescence signals)
      on two flow cytometry platforms, BD FACSCanto II and BD FACSCalibur. Results.
      Results from both assays were highly congruent, with an overall r(2) >= 0.99 (all
      specimen types included), a linear correlation across all CD34(+) cell
      frequencies and concentrations, and an almost ideal steepness of the trend line.
      CONCLUSIONS: Both assays functioned reliably. Being based on single-platform
      International Society of Hematotherapy and Graft Engineering (ISHAGE) guidelines
      and similar staining methods, both assays essentially come to identical results.
      For most specimen types, the viability of CD34(+) cells was equal to overall
      leukocyte viability. In summary, in the hands of an experienced technician, the
      BDTM SCE kit and the BC Stem-Kit are equivalent. The infrequent user might derive
      benefit from the fact that counting spheres are pre-pipetted into the Trucount
      tube for the SCE kit, making this assay less susceptible to pipetting inaccuracy.

PMID- 21077729
TI  - Characterization of hematopoietic stem cell subsets from patients with multiple
      myeloma after mobilization with plerixafor.
AB  - BACKGROUND AIMS: Previous studies have demonstrated that the combination of
      granulocyte-colony-stimulating factor (G-CSF) + plerixafor is more efficient in
      mobilizing CD34(+) hematopoietic stem cells (HSC) into the peripheral blood than
      G-CSF alone. In this study we analyzed the impact of adding plerixafor to G-CSF
      upon the mobilization of different HSC subsets. METHODS: We characterized the
      immunophenotype of HSC subsets isolated from the peripheral blood of eight
      patients with multiple myeloma (MM) before and after treatment with plerixafor.
      All patients were supposed to collect stem cells prior to high-dose chemotherapy
      and consecutive autologous stem cell transplantation, and therefore received
      front-line mobilization with 4 days of G-CSF followed by a single dose of
      plerixafor. Samples of peripheral blood were analyzed comparatively by flow
      cytometry directly before and 12 h after administration of plerixafor. RESULTS:
      The number of aldehyde dehydrogenase (ALDH)(bright) and CD34(+) cells was
      significantly higher after plerixafor treatment (1.2-5.0 and 1.5-6.0 times; both
      P < 0.01) and an enrichment of the very primitive CD34(+) CD38(-) and
      ALDH(bright) CD34(+) CD38(-) HSC subsets was detectable. Additionally, two
      distinct ALDH(+) subsets could be clearly distinguished. The small ALDH(high)
      subset showed a higher number of CD34(+) CD38(-) cells in contrast to the total
      ALDH(bright) subpopulation and probably represented a very primitive
      subpopulation of HSC. CONCLUSIONS: A combined staining of ALDH, CD34 and CD38
      might represent a powerful tool for the identification of a very rare and
      primitive hematopoietic stem cell subset. The addition of plerixafor mobilized
      not only more CD34(+) cells but was also able to increase the proportion of more
      primitive stem cell subsets.

PMID- 21077731
TI  - Bioequivalence comparison of a new freezing bag (CryoMACS((r))) with the
      Cryocyte((r)) freezing bag for cryogenic storage of human hematopoietic
      progenitor cells.
AB  - BACKGROUND AIMS: We investigated two different plastic freezing bags, namely the
      most recently U.S. Food and Drug Administration (FDA)-approved CryoMACS((r))
      freezing bag (200-074-402) from Miltenyi Biotec and the familiar Cryocyte((r))
      freezing bag (R4R9955) from (Baxter Healthcare, Deerfield, IL, United States) for
      the cryogenic storage of human hematopoietic progenitor cells (HPC). METHODS: The
      study material consisted of 12 frozen HPC pairs (= 24 transplant units) that were
      no longer needed for autologous treatment of patients. After thawing, one unit of
      a pair was transferred into the Miltenyi (M) bag; the other unit remained in the
      original Baxter (B) bag. After refreezing both units, all units were stored again
      under cryogenic conditions either partially immersed in liquid nitrogen (n = 22)
      or in the vapor phase over liquid nitrogen, n = 2, <-170 degrees ) before
      thawing. RESULTS: The correlation coefficients (r) between the results obtained
      from the two bag types were high for white blood cells (WBC) content (r = 0.98),
      mononuclear cells (MNC) (r = 0.97), lymphocytes (r = 0.98), monocytes (r = 0.96),
      membrane integrity (r = 0.93), concentration of 'free' hemoglobin (r = 0.97) and
      hemolysis rate (r = 0.95). With regard to clonogenicity, there were no
      significant differences (Student's paired t-test) for the three parameters
      investigated [i.e. total number of colonies, including the numbers of burst
      forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage
      (CFU-GM) colonies, respectively). CONCLUSIONS: The CryoMACS freezing bag 200-074
      402 is bioequivalent to the Cryocyte freezing container R4R9955. An advantageous
      feature of the CryoMACS is that its double-sterile wrapping provides additional
      safety regarding potential cross-contamination during cryogenic storage.

PMID- 21077732
TI  - Gene expression profiles following intracoronary injection of mesenchymal stromal
      cells using a porcine model of chronic myocardial infarction.
AB  - BACKGROUND AIMS: We evaluated the therapeutic potential of injection of in vitro
      differentiated bone marrow mesenchymal stromal cells (MSC) using a swine model.
      METHODS AND RESULTS: Myocardial infarction was induced by coronary occlusion.
      Three groups (n = 5 each) were analyzed: one group received an injection of 17.8
      +/- 9.3 * 10(6) 5-azacytidine-treated allogeneic MSC 1 month after infarction; a
      placebo group received an injection of medium; and controls were kept untreated.
      After 4 weeks, heart samples were taken from three infarcted areas,
      interventricular septa, ventricles and atria. Gene expression profiles of genes
      related to contractility (Serca2a), fibrosis (Col1a1), cardiomyogenesis (Mef2c,
      Gata4 and Nkx2.5) and mobilization of stem cells (Sdf1, Cxcr4 and c-kit) were
      compared by quantitative real-time PCR (qRT-PCR). Gene expression profiles varied
      in different heart areas. Thus Serca2a expression was reduced in infarcted groups
      in all heart regions except for the left ventricles, where Col1a1 was
      overexpressed. The expression of genes related to cardiomyogenesis decreased in
      the infarcted zones and left atria compared with healthy hearts. Interestingly,
      increased expression of Cxcr4 was detected in infarcted regions of MSC-treated
      pigs compared with the placebo group. CONCLUSIONS: Infarction induced changes in
      expression of genes involved in various biologic processes. Genes involved in
      cardiomyogenesis were downregulated in the left atrium. The intracoronary
      injection of MSC resulted in localized changes in the expression of Cxcr4.

PMID- 21077733
TI  - Deglutition and respiratory patterns during sleep in younger adults.
AB  - CONCLUSION: Deglutition was infrequent and displayed unique patterns during sleep
      in healthy younger adults. OBJECTIVES: The deglutition, electroencephalographic
      arousal, and respiratory phase patterns during sleep in younger adults were
      investigated. METHODS: Ten younger adults were examined via time-matched
      recordings of polysomnography and surface electromyography. RESULTS: During
      sleep, swallowing was infrequent and absent for long periods. The mean number of
      swallows per hour during the total sleep time was 2.4 +/- 1.0. The mean longest
      deglutition-free period was 68.8 +/- 24.8 min. Most deglutition occurred in
      association with spontaneous electroencephalographic arousal. Deglutition was
      related to the sleep stage. The mean number of swallows per hour was 11.2 +/- 8.1
      during stage 1 sleep, 1.9 +/- 1.0 during stage 2 sleep, 0.5 +/- 1.5 during stage
      3 sleep, and 0.2 +/- 0.5 during stage 4 sleep. The deeper the sleep stage, the
      lower the mean deglutition frequency. The mean number of swallows per hour was
      1.9 +/- 1.7 during rapid eye movement sleep. The deeper the sleep stage, the
      lower the mean arousal frequency and the lower the mean ratio of arousal with
      deglutition to arousal. Approximately 60% of swallows were followed by arrested
      breathing and approximately 25% by expiration.

PMID- 21077734
TI  - Saccharomyces boulardii and Candida albicans experimental colonization of the
      murine gut.
AB  - Saccharomyces boulardii has been and continues to be extensively used as a
      probiotic, with only rare associations with fungemia. This study evaluated the
      virulence of this yeast when given as a probiotic, and its role in preventing
      gastrointestinal (GI) colonization by Candida. Adult male Crl:CD1 (ICR) BR mice
      were given S. boulardii orally in three different doses or normal saline for 14
      days. Stool cultures were performed at the time of discontinuation of yeast
      administration, as well as 1 and 2 weeks later. Gut colonization was proportional
      to the given dose but lasted only 1 week and no dissemination of the yeast was
      detected. S. boulardii was also given for 2 and 4 weeks to mice fed chow
      containing Candida albicans. S. boulardii in the gut did not affect Candida GI
      colonization. These findings suggest that oral administration of S. boulardii
      induces a substantial but short term increase of this yeast in the intestinal
      lumen and administration of the probiotic does not prevent subsequent GI
      colonization by C. albicans.

PMID- 21077735
TI  - Palatal mucormycosis in patients with hematologic malignancy and stem cell
      transplantation.
AB  - We present two patients with acute myelogenous leukemia who developed palatal
      mucormycosis, as well as a review of 15 well described reported cases of the same
      condition in patients who had hematologic malignancy and had undergone
      hematopoietic stem cell transplantation. Early diagnosis of palatal mucormycosis
      requires high suspicion of the disease along with a thorough oral examination.
      Mucormycosis is a devastating disease with a high mortality rate, thereby
      stressing the importance for early appropriate antifungal therapy in
      immunocompromised patients with palatal lesions while awaiting the results of
      histopathology and cultures.

PMID- 21077736
TI  - Exposure to host or fungal PGE2 abrogates protection following immunization with
      Candida-pulsed dendritic cells.
AB  - Candida albicans produces an immunomodulatory oxylipin from arachidonic acid that
      is structurally identical to host prostaglandin E2 (PGE2). In terms of host
      immune responses, PGE2 can promote Th2 responses, which are non-protective
      against fungal infections. We investigated the effect of host or fungal PGE2 on
      murine bone marrow-derived dendritic cell (DC) cytokine production, and the
      ability to immunize mice against systemic infection with C. albicans. We used GM
      CSF to produce myeloid DCs (GM-DCs) and FLT-3L to enrich for plasmacytoid DCs (FL
      DCs). In the presence of hyphae, PGE2 promoted Th2 cytokine production and
      suppressed Th1 cytokine production. Immunization with yeast-pulsed DCs but not
      hyphae-pulsed DCs lead to a reduction in kidney fungal burden during systemic
      infection, which was most dramatic with FL-DCs. However, exposure to either host
      or fungal PGE2 during antigenic stimulation abrogated the ability of yeast-pulsed
      DCs to protect against infection. The lack of protection was associated with a
      trend towards reduced Th1 cytokines and increased Th2 cytokines in the spleen.
      However, the pattern of protection did not completely match cytokine expression.
      Locally, in FL-DC pulsed mice, reduced Th1 and exacerbated Th2 and Th17 cytokines
      were only detected in the kidneys of mice that did not show reductions in fungal
      burden after vaccination. This indicates that host or fungal PGE2 can shift
      adaptive responses in favor of the pathogen and that uncontrolled Th17 responses
      are detrimental during systemic infection.

PMID- 21077737
TI  - Report on the Second International Workshop on interim positron emission
      tomography in lymphoma held in Menton, France, 8-9 April 2010.
AB  - One hundred and fifty hemato-oncologists and nuclear medicine specialists from
      more than 20 countries joined in April 2010 the 2-day Second International
      Workshop on interim PET in lymphoma. During the nuclear medicine session the
      advantages of the five-point scale Deauville criteria for interim PET reporting
      over the other sets of visual criteria were presented. The specific problems of
      PET reporting in escalation/de-escalation trials in Hodgkin lymphoma (HL) were
      addressed as well as the limitations of visual analysis for early PET evaluation
      in non-Hodgkin lymphoma (NHL). The applicability, efficacy, and reproducibility
      of quantitative criteria (DeltaSUV(max) analysis and tumor/liver SUV ratio) for
      interim PET in NHL were reported. In retrospective and prospective series. Some
      of the interim PET-based clinical trials ongoing worldwide in HL and NHL were
      reported. In early-stage HL, three trials aimed at determining the feasibility of
      omitting radiotherapy in interim PET negative patients, and in advanced-stage HL
      two PET-based ABVD escalation or BEACOPP de-escalation trials, in NHL two studies
      reported preliminary results of interim PET in follicular lymphoma, in DLBCL a
      round-table discussion pointed out the lack of definite criteria for interim PET,
      and a few observational studies in DLBCL reported the comparison of the various
      techniques of interim PET reporting (visual versus quantitative). The preliminary
      results of two international validation studies of the five-point scale criteria
      in HL and NHL launched in 2009 were reported. The presentations of the meeting
      are available on http://eitti.free.fr.

PMID- 21077738
TI  - Surface antigens analysis reveals significant expression of candidate targets for
      immunotherapy in adult acute lymphoid leukemia.

PMID- 21077739
TI  - Analysis of genome-wide methylation and gene expression induced by 5-aza-2'
      deoxycytidine identifies BCL2L10 as a frequent methylation target in acute
      myeloid leukemia.
AB  - Epigenetic changes play a role in the pathogenesis of myeloid malignancies, and
      hypomethylating agents have shown efficacy in these diseases. We studied the
      apoptotic effect, genome-wide methylation, and gene expression profiles in HL60
      cells following 5-aza-2'-deoxycytidine (decitabine; DAC) treatment, using
      microarray technologies. Decitabine treatment resulted in a decrease in global
      DNA methylation, corresponding to 4876 probeset IDs with significantly reduced
      methylation levels, while the expression of 2583 IDs was modified. The integrated
      analysis identified 160 genes demethylated and up-regulated by decitabine, mainly
      including development and differentiation pathway genes. Gene targets of Polycomb
      group protein regulation were overrepresented in this group. Apoptosis was
      induced by decitabine, and apoptosis-specific PCR arrays more precisely indicated
      decitabine-induced up-regulation of 13 apoptosis-related genes, in particular DAP
      kinase 1 and BCL2L10. Correspondingly, in primary patient samples, BCL2L10 was
      hypermethylated in 45% of AML, 43% of therapy-related myeloid neoplasms, 12% of
      MDS, and in none of the controls. In conclusion, decitabine induces global
      demethylation and gene expression, in particular of Polycomb target genes
      involved in development and differentiation pathways. The apoptotic gene BCL2L10
      is a frequent target for aberrant promoter methylation in patients with acute
      leukemia, de novo and therapy-related.

PMID- 21077740
TI  - Treatment of multiple myeloma in the elderly: realities and hopes.
AB  - Until recently, combination chemotherapy with melphalan and prednisone (MP) has
      remained the most widely accepted treatment option for elderly patients with
      multiple myeloma (MM). However, since the availability of new and more active
      drugs, several groups have compared in several phase III trials the efficacy and
      safety of MP versus MP-based therapies including new agents such as thalidomide
      (MPT) or bortezomib (MPV). In all these studies response rate and progression
      free survival were superior in patients receiving MPT or MPV. However, these new
      combinations are not without side effects, and the incidence of grade 3 and 4
      toxicities is higher than that reported with MP. Besides, the median duration of
      the complete remissions obtained with these new combinations is still
      insufficient, ranging from 15 to 27 months, and new therapeutic alternatives are
      still needed in this subset of patients. The purpose of this review article is to
      summarize the currently available data in the front-line treatment of elderly
      patients with MM and to discuss which questions are still unsolved in the
      management of this subset of patients.

PMID- 21077741
TI  - Posttranscriptional regulation of the p85alpha adapter subunit of
      phosphatidylinositol 3-kinase in human leukemia cells.
AB  - Constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling has
      been observed in up to 70% of acute myeloid leukemia. Class I(A) PI3K consists of
      a catalytic subunit (p110alpha, p110beta, p110delta) and an adapter subunit
      (p85alpha, p55alpha, p50alpha, p85beta, p55gamma). The p85alpha adapter subunit
      stabilizes the catalytic p110 subunit and recruits p110 to the plasma membrane.
      In addition, p85alpha inhibits the basal activity of p110alpha and can negatively
      regulate signal transduction, as shown for insulin and GM-CSF receptor signaling.
      Here, we describe that the expression of p85alpha is posttranscriptionally
      regulated in several human and murine leukemia cell lines and in a Hodgkin
      lymphoma cell line (CO) by translational repression. A detailed analysis of CO
      cells revealed that both wild type and a mutated p85alpha mRNA are detectable at
      similar ratios in the nucleus and polysomes. However, while the mutated p85alpha
      protein is expressed in CO cells, translation of the wild type p85alpha mRNA is
      completely inhibited. Ectopic expression of wild type p85alpha from a retroviral
      vector is suppressed in CO cells and in five out of six leukemia cell lines. Our
      data indicate that leukemia cells can regulate the expression of p85alpha by
      posttranscriptional regulation.

PMID- 21077742
TI  - Expression of tumor-associated macrophages and vascular endothelial growth factor
      correlates with poor prognosis of peripheral T-cell lymphoma, not otherwise
      specified.
AB  - To elucidate the expression of tumor-associated macrophages (TAMs) and vascular
      endothelial growth factor (VEGF) in peripheral T-cell lymphoma, not otherwise
      specified (PTCL-NOS), and their correlation with patient clinical characteristics
      and overall survival (OS), immunohistochemistry stains for CD68 and VEGF were
      applied to 38 tissue specimens of PTCL-NOS. The CD68+ cell content and VEGF
      positive rates were significantly higher in PTCL-NOS tissues (p < 0.05). TAMs
      were significantly related to bone marrow invasion, international prognostic
      index (IPI) score, and response to treatment (p < 0.05). The 2-year OS of the
      high-TAMs-expression group (>50/hpf) was 22.2%, and that of the low-TAMs
      expression group (<50/hpf) was 52.8% (p < 0.05). The expression of VEGF was
      closely related to tumor staging, bone marrow invasion, and IPI score (p < 0.05).
      The 2-year OS of the VEGF-positive group was 25.4%, and that of the VEGF-negative
      group was 83.3% (p < 0.01). Therefore, TAMs and VEGF, which were significantly
      correlated to prognosis of the disease, may be involved in the tumorigenesis,
      progression, invasion, and angiogenesis of PTCL-NOS.

PMID- 21077743
TI  - Caring beyond cure: quality of life after high-dose chemotherapy for patients
      with relapsed Hodgkin lymphoma.

PMID- 21077744
TI  - DEPTOR expression and response to thalidomide: toward a new therapeutic target in
      multiple myeloma?

PMID- 21077745
TI  - Novel influenza A (H1N1) in patients with hematologic disease.
AB  - Patients with hematologic disease are likely to be at increased risk for
      infection with influenza. We retrospectively analyzed 11 cases of patients with
      hematologic disease who were infected with pandemic H1N1 virus in our department,
      including their clinical manifestations, laboratory and imaging findings,
      outcomes of antiviral therapy, and factors associated with mortality. Notably,
      nine patients had lower respiratory tract disease. Five patients progressed to
      respiratory failure and eventually died, despite treatment with antivirals and/or
      corticosteroids and/or mechanical ventilation. We concluded that H1N1 2009
      infection was associated with a severe course and high rate of mortality in
      patients with hematologic disease, and early diagnosis and antiviral treatment
      were important to reduce the rate of severe complications and mortality.

PMID- 21077747
TI  - Delivering value and driving advocacy in medical publications. Abstracts of the
      6th Annual Meeting of the International Society for Medical Publication
      Professionals. April 19-21, 2010. Arlington, Virginia, USA.

PMID- 21077746
TI  - Excessive sleepiness: under-recognized and essential marker for sleep/wake
      disorder management.
AB  - BACKGROUND: Research during the past few decades has provided substantial
      evidence indicating that excessive sleepiness (ES) and associated sleep/wake
      disorders can result in significant morbidity and mortality. However,
      symptomatology (e.g., ES) and the relationships among common morbidities (e.g.,
      cardiovascular disease, metabolic disorders, mood impairment) and sleep/wake
      disorders remain under-recognized in clinical practice, particularly in primary
      care. Yet assessment of sleep/wakefulness and associated symptoms can often be
      easily conducted in the primary care setting, providing valuable information to
      facilitate the diagnosis and management of sleep/wake disorders. OBJECTIVE: To
      provide a conceptual and educational framework that helps primary care physicians
      comprehensively assess, differentially diagnosis, and appropriately manage
      patients presenting with ES or ES-related sleep/wake disorders. METHODS:
      Comprised of six sleep specialists and six primary care physicians, the
      Sleep/Wake Disorders Working Group (SWG) used a modified, two-round Delphi
      approach to create and harmonize consensus recommendations for the assessment,
      diagnosis, treatment, and ongoing management of patients with common sleep/wake
      disorders related to ES. RESULTS: After a review of the relevant literature, the
      SWG arrived at consensus on a number of clinical recommendations for the
      assessment and management ES and some of the most commonly associated sleep/wake
      disorders. Ten consensus statements - five each for assessment/diagnosis and
      treatment/ongoing care - were created for ES, insomnia, obstructive sleep apnea,
      circadian rhythm disorders, restless legs syndrome, and narcolepsy. CONCLUSION:
      ES and ES-related sleep/wake disorders are commonly encountered in the primary
      care setting. By providing an educational framework for primary care physicians,
      the SWG hopes to improve patient outcomes by emphasizing recognition, prompt
      diagnosis, and appropriate ongoing management of ES and associated sleep/wake
      disorders.

PMID- 21077749
TI  - Both pain and fatigue are important possible determinants of disability in
      patients with the Ehlers-Danlos syndrome hypermobility type.

PMID- 21077748
TI  - Experimental 70% hydrofluoric acid burns: histological observations in an
      established human skin explants ex vivo model.
AB  - BACKGROUND: Hydrofluoric acid (HF) is particularly dangerous due to the potential
      for systemic effects and induction of severe skin necrosis through two
      mechanisms: corrosiveness and local tissue toxicity. In addition, because it is
      only partially dissociated (pK(a) 3.2), it is capable of penetrating deeply into
      tissues. There is a lack of experimental studies that objectively characterize
      the behavior of HF diffusion into human skin, specifically the kinetics of tissue
      penetration resulting in severe cellular lesions. METHODOLOGY/PRINCIPAL FINDINGS:
      We describe the cutaneous effects of HF using an established ex vivo human skin
      model. The diffusion of 70% HF starts within the first minute of contact at the
      epidermal surface and after 2 min reaches the basal layer. In the subsequent
      minute, the epidermis is destroyed and lesions appear in the papillary dermis
      after 4 min. Soon after, damage appears in the upper reticular dermis. Thus, 70%
      HF needs only 5 min of contact to completely penetrate human skin explants. This
      experiment is reproducible and corroborates previous studies and clinical effects
      reported in accidental HF exposures. CONCLUSION/SIGNIFICANCE: This study shows
      that the management of HF chemical skin exposure is a question of minutes,
      especially for initial decontamination. These experimental observations could be
      useful for objectively comparing skin decontamination methods. Further studies
      should help to confirm these preliminary results.

PMID- 21077750
TI  - Development of sponge-like dressings for mucosal/transmucosal drug delivery into
      vaginal cavity.
AB  - The aim of the present work was the development of vaginal sponge-like dressings
      based on chitosan ascorbate (CS) and on hyaluronic acid sodium salt/lysine
      acetate (HAS) combination. Sponge-like dressings were prepared by freeze-drying
      and characterized for mechanical resistance and mucoadhesion. CS dressings show
      higher mechanical and mucoadhesion properties in comparison with HAS dressing.
      The enzymatic inhibition properties of the dressings were evaluated in vitro
      against carboxipeptidase A in view of their employment for vaginal delivery of
      peptidic drugs. All the dressings were able to inhibit carboxipeptidase activity;
      CS dressings, independently of polymer MW, completely inhibited enzyme activity.
      Release and penetration enhancement properties of the dressings loaded with a
      high molecular weight hydrophilic molecule, fluorescein isothiocyanate dextran
      (FD4), were assessed. CS dressings were able to prolong FD4 release. All the
      dressings showed penetration enhancement properties into pig vaginal mucosa
      although to a different extent: greater for dressings based on CS than for that
      containing HAS. Moreover, CS dressings demonstrated intrinsic antimicrobial
      properties. The suitability of sponge-like systems for the treatment of vaginal
      infections was assessed by loading the CS dressing characterized by the best
      mechanical and antimicrobial properties with an antibiotic drug (clyndamicin-2
      phosphate) and by checking drug release.

PMID- 21077753
TI  - The influence of thermal history on the physical behavior of poly(ethylene
      glycol) (PEG).
AB  - OBJECTIVES: To investigate the influence of thermal history on the physical
      behavior of poly(ethylene glycol) (PEG), commonly used as a pharmaceutical
      excipient. MATERIALS AND METHODS: Rheological investigations together with SEM
      imaging and solid state analysis by XRPD and DSC were used to characterize PEG as
      starting material, as well as PEG:lactose monohydrate granules. For granulation
      experiments PEG 6000 was used and for further investigations of physicochemical
      properties, three M(w) of PEG (3000-10000) with different thermal histories
      obtained by melting the PEG followed by solidification with specific cooling
      rates. RESULTS AND DISCUSSION: More uniform granules were obtained when fast
      cooled PEG was used as binder. XRPD suggested similar crystallinity for the
      different M(w) and thermal history did not influence the results drastically.
      However, rheological analysis and DSC measurements indicated different melting
      behavior dependent on the M(w) of PEG. PEG 6000 and 10000 were affected by the
      thermal treatment where stepwise melting was observed with slower cooling rate
      probably due to increased formation of extended structures. CONCLUSIONS:
      Increased cooling rate gives rise to increased randomness, more folded structure
      of PEG, which reflects in the outcome of the granulation process.

PMID- 21077754
TI  - Exploring mobility options for children with physical disabilities: a focus on
      powered mobility.

PMID- 21077755
TI  - Expression of double strand DNA breaks repair genes in pterygium.
AB  - PURPOSE: The alteration in the expression of some genes and proteins responsible
      for chosen DNA repair pathways in pterygium pathogenesis were studied. This study
      was focused on the examination of the expression of genes and RAD50 protein
      taking part in homologous recombination. METHODS: Peripheral blood lymphocytes,
      samples of pterygium tissue, samples of conjunctiva of patients suffering from
      pterygium as well as peripheral blood lymphocytes and conjunctiva of patients
      from the control group were examined. In order to identify genes products from
      RNA, Ribonuclease Protection Assai method was applied. LIM15, RAD50, RAD54,
      RAD52, MRE11, XRCC2, XRCC3, RAD51, RAD51B, RAD51C, RAD51D genes transcripts were
      detected. Expression of RAD50 protein was analyzed immunohistochemically.
      RESULTS: Peripheral blood lymphocytes analyses revealed lower level of RAD50 gene
      expression in the pterygium patients compared to the control group and the
      increased expression of XRCC2, XRCC3 and RAD51 genes in patients with pterygium,
      who declared the recurrence of the lesion in comparison to the patients with
      primary pterygium. Lower expression of the RAD54 gene in pterygium tissue
      comparing to conjunctiva from the eyes with pterygium was found. An expression of
      RAD50 gene in the conjunctiva originating from eyes with pterygium in comparison
      to the conjunctiva of control group was shown to be considerably higher.
      Expression of RAD50 protein in pterygium squamous epithelial cells was
      significantly higher than in conjunctiva from control group. CONCLUSION: There
      may exist a relationship between pterygium pathogenesis and damages of double
      strand DNA, however, the elucidation of its exact nature needs further study.

PMID- 21077756
TI  - OCT findings in young asymptomatic subjects carrying familial BEST1 gene
      mutations.
AB  - PURPOSE: Best disease is an autosomal dominant retinal degeneration characterized
      by the presence of yellow lesions in the macula causing decreased central visual
      acuity at later stages. Best disease is caused by heterozygous mutations in
      BEST1, a gene located at chromosome 11q13. In the present study, we describe the
      clinical and molecular analysis of two multigenerational families with Best
      disease and correlate the optical coherence tomography (OCT) findings in
      asymptomatic and symptomatic subjects carrying BEST1 mutations. METHODS: Two
      Mexican families with 3 affected generations each were studied. Probands
      underwent full ophthalmologic examination including fundus examination,
      fluorescent angiography (FAG), and electro-oculogram (EOG). Fourier-domain 3D OCT
      was performed in a number of symptomatic and asymptomatic subjects from these two
      pedigrees. PCR amplification and automated nucleotide sequencing of the 11 exons
      of the BEST1 gene in genomic DNA were also performed. RESULTS: Eighteen members
      of family 1 were molecularly tested. Seven subjects, including 4 young
      asymptomatic patients, carried a W24C heterozygous mutation in BEST1. OCT imaging
      in a 6-year-old asymptomatic patient carrying this mutation did not demonstrate
      retinal lesions. Fifteen subjects from family 2 were molecularly tested. Four
      patients, including 2 asymptomatic subjects, carried a heterozygous Q293K BEST1
      mutation. OCT imaging in an asymptomatic 8-year-old individual with the Q293K
      mutation demonstrated bilateral subfoveal lesions and unilateral serous retinal
      detachment. Symptomatic patients showed severe retinal lesions by OCT.
      CONCLUSIONS: Our results add to the clinical, imaging, and molecular knowledge of
      Best disease and suggest that OCT can recognize retinal lesions in some
      asymptomatic carriers of BEST1 mutations as early as 8 years of age.

PMID- 21077757
TI  - Obesity and microvascular invasion in hepatocellular carcinoma.
AB  - BACKGROUND: We hypothesized that hepatocellular carcinoma (HCC) patients with
      higher Body Mass Index (BMI) might have more microvascular invasion (MVI) in
      their tumors. METHODS: Records from 138 consecutive patients who underwent
      surgery at Columbia University Medical Center from January 1, 2002 to January 9,
      2008 were evaluated. RESULTS: 40 patients (29%) had MVI, including 14% with BMI
      <25, 31% with BMI = 25-30, and 40% with BMI >30 (p = .05). However, only maximum
      alpha-fetoprotein was significantly associated with overall mortality in a Cox
      model. CONCLUSIONS: MVI was associated with obesity. A better understanding of
      the mechanism of this association may lead to interventions for the treatment and
      prevention of HCC.

PMID- 21077758
TI  - Hb S [beta6(A3)Glu->Val, GAG>GTG] in Mexican Mestizos: frequency and analysis of
      the 5' beta-globin haplotype.
AB  - Between 1978 and 2009, we studied 1,863 Mexican Mestizo patients with clinical
      data compatible with a hemoglobinopathy. Of these patients, 382 had some
      hemoglobin (Hb) abnormality (20.5%), 128 had a sickle cell hemoglobinopathy,
      representing a general frequency of 6.9%, which is similar to the percentage
      observed in previous studies on Mexican Mestizos. We analyzed the 5' beta-globin
      haplotype (5'Hp) in 79 unrelated beta(S) chromosomes (26 beta(S)/beta(S), 14
      beta(S)/beta(Thal), nine beta(S)/beta(A) and four beta(S)/beta(D)), and four
      haplotypes were observed: 72.2% CAR 24.1% Benin, 2.5% Senegal and 1.2% Cameroon;
      the last two are reported for first time in Mexico. In some Latin American
      populations such as Brazil, the Bantu haplotype predominates, while in others
      such as Jamaica, the Benin haplotype is the most frequent, showing heterogeneity
      of African genes as a consequence of different regions involved in the slave
      trade.

PMID- 21077759
TI  - Coinheritance of alpha-thalassemia decreases the risk of cerebrovascular disease
      in a cohort of children with sickle cell anemia.
AB  - The study estimated alpha-thalassemia (alpha-thal) prevalence and assessed its
      associations with clinical and hematological features in a random sample of
      Brazilian children with sickle cell anemia (208 Hb SS and 13 Hb S-beta0-thal).
      alpha-Thalassemia genotyping was carried out by multiplex polymerase chain
      reaction (m-PCR) for seven alleles. Clinical and hematological data were
      retrieved from the 221 children's medical files. Their ages ranged from 2.5 to
      10.4 years. Of the Hb SS children, 27.9% carried -alpha(3.7)/alphaalpha and 1.4% 
      alpha(3.7)/-alpha(3.7). The presence of alpha-thal was significantly associated
      with reduction in MCV, MCH, WBC values and reticulocyte counts. No significant
      association with blood transfusion or acute chest syndrome (ACS), was found.
      alpha-Thalassemia genotypes were strongly associated with reduction in risk for
      cerebrovascular disease (CVD) (conditional and abnormal transcranial Doppler or
      stroke; p = 0.007). The interaction of alpha-thal with other modulating factors
      should be investigated in order to define subphenotypes of the disease and to use
      them as clinical tools in the follow-up care of patients.

PMID- 21077760
TI  - beta-globin gene haplotypes linked with the Hb D-Punjab [beta121(GH4)Glu->Gln,
      GAA>CAA] mutation in eastern India.
AB  - Hb D-Punjab [beta121(GH4)Glu->Gln] is prevalent in the northern states of the
      Indian subcontinent. Due to inadequate data from Asian countries, the origin and
      spread of the Hb D-Punjab mutation are uncertain. In a study of sickle cell
      hemoglobinopathies, we detected the Hb D-Punjab mutation in 25 subjects from 11
      unrelated Agharia families. Twelve cases were Hb S [beta6(A3)Glu->Val]/Hb D
      Punjab compound heterozygotes and 13 were Hb D trait carriers. In 76.0% of the
      cases, the beta(D) gene was linked to haplotype I, whereas 24.0% had a novel
      haplotype. None of the haplotypes matched the beta(A) haplotype of the local
      population. In view of the ancestral origin of the subjects and the high
      prevalence of the beta(D) gene in the states of northern India, we suggest a
      North Indian origin for the beta(D) mutation in our population. The finding of a
      novel haplotype in eastern India supports the hypothesis of a multicentric origin
      of this mutation.

PMID- 21077761
TI  - Molecular updating of beta-thalassemia mutations in the Upper Egyptian
      population.
AB  - We have updated the dataset of the molecular spectrum of the beta-thalassemia
      (beta-thal) in Upper Egypt. Buccal swabs were analyzed from 94 unrelated patients
      with beta-thal major (beta-TM) using reverse dot-blot and multiplex amplification
      refractory mutation system-polymerase chain reaction (ARMS-PCR). The most
      frequent mutation was IVS-I-110 (G>A) (57%). The IVS-I-110, IVS-I-6 (T>C) and IVS
      I-1 (G>A) mutations accounted for 87% of the beta-thal anomalies. The codon 39
      (C>T) and frameshift codon (FSC) 6 (-A) (GAG>-GG) mutations were only detected in
      Al-Minya and Qina, respectively. We did not observe the IVS-II-745 (C>G) or -101
      (C>T) mutations. Forty-three percent of Upper Egyptians were homozygotes. Our
      efforts were an important step to complete the mutation map of beta-thal in Egypt
      restricted to Cairo and the Nile Delta regions. This study will help to develop
      preventative programs for Upper Egyptians. It addressed the genetic drift of the
      beta-thal gene mutations in Africa, Asia, and Europe.

PMID- 21077762
TI  - Bayesian estimates of the prevalence of beta-thalassemia trait in voluntary blood
      donors of central India: a survey.
AB  - Early detection of beta-thalassemia (beta-thal) trait is important. Voluntary
      blood donors represent an important group who are accessible and cooperative for
      this purpose. However, the usefulness of this population in beta-thal trait
      detection programs has not been studied in India. We conducted a hematological
      survey of 5,045 blood donors who visited the Bhopal Memorial Hospital & Research
      Centre, Bhopal in central India. Using robust Bayesian methods, we estimated the
      prevalence of beta-thal trait. The overall prevalence of beta-thal trait in the
      study population was 9.59% [95% confidence interval (95% CI) 8.78-10.4%]. The
      prevalence of beta-thal trait varied across the states of origin and within the
      state of Madhya Pradesh. We observed a cline effect for beta-thal trait
      prevalence in relation to the latitude (p = 0.024). We conclude that blood donors
      offer an attractive adjunct to beta-thal trait detection in national programs.
      Our study also offers insights into the beta-thal trait gene flow and migration
      in India.

PMID- 21077763
TI  - Hb East Timor [beta80(EF4)Asn->His, AAC>CAC (HBB c.241A>C)], a variant hemoglobin
      associated with normal hematology.
AB  - Routine hemoglobin (Hb) analyses identified a new beta-globin variant in a family
      from East Timor. The red cell indices were within normal limits for all affected
      family members. The variant is due to a missense mutation at amino acid codon 80
      (AAC>CAC) which results in the substitution of histidine for asparagine.

PMID- 21077764
TI  - Hb Cambridge-MA [beta144(HC1)-beta146(HC3)Lys-Tyr-His->0 (HBB c.433 A>T)]: a new
      high oxygen affinity variant.
AB  - A new beta hemoglobin (Hb) variant, Hb Cambridge-MA [beta144(HC1)beta146(HC3)Lys
      Tyr-His->0 (AAG>TAG) (HGVS: HBB c.433 A>T] is described. The variant was
      characterized by high performance liquid chromatography (HPLC), alkaline, acid,
      globin chain and capillary electrophoresis, isoelectric focusing (IEF), heat and
      isopropanol stability, p50 analyses, intact globin mass spectrometry (MS) and DNA
      sequencing. The new variant shows high oxygen (O2) affinity and is associated
      with mild polycythemia.

PMID- 21077765
TI  - Hb Sarrebourg [beta131(H9)Gln->Arg, CAG>CGG] in Turkey.
AB  - We describe Hb Sarrebourg [beta131(H9)Gln->Arg, CAG>CGG] in four heterozygous
      members of a Turkish family. It was associated with iron deficiency in the
      proband.

PMID- 21077766
TI  - A dyserythropoietic anemia associated with homozygous Hb Plasencia
      [alpha125(H8)Leu->Arg (alpha2)] (HBA2:c.377T>G), a variant with an unstable alpha
      chain.
AB  - A female patient of Portuguese origin, who was born to consanguineous parents,
      presented with moderate anemia, mild jaundice and splenomegaly. Bone marrow
      aspiration showed an erythroid hyperplasia and binucleate erythroblasts, evoking
      a congenital dyserythropoietic anemia, type II (CDA II). Although microcytosis
      cast some doubt on the diagnosis, investigation was pursued along this line. The
      CDA II was finally ruled out as underglycosylation of band 3, remnants of
      endoplasmic reticulum cisternae and mutations in the SEC23B gene were all
      missing. On the other hand, analysis of the alpha-globin genes showed a base
      substitution at codon 125 (CTG->CGG) of the alpha2-globin gene, ascertaining a
      homozygosity for Hb Plasencia (HBA2:c.377T>G). This variant has an unstable alpha
      chain. In the absence of a thorough work-up, dyserythropoietic anemia associated
      with hemoglobin (Hb) variants having a moderately unstable alpha chain, may be
      mistaken for CDA II.

PMID- 21077767
TI  - Molecular screening of the Hbs Constant Spring (codon 142, TAA>CAA, alpha2) and
      Pakse (codon 142, TAA>TAT, alpha2) mutations in Thailand.
AB  - Hb Constant Spring [Hb CS, alpha142(H19)Term] and Hb Pakse [alpha142(H19)Term]
      occur from the mutation in the termination codon of the alpha2-globin gene,
      TAA>CAA (->Gln) and TAA>TAT (->Tyr), respectively. They are the most common
      nondeletional alpha-thalassemia (alpha-thal) variants causing Hb H disease in
      Southeast Asia. In this study, 587 cord blood samples were screened for the Hb CS
      and Hb Pakse mutations by a dot-blot hybridization technique using
      oligonucleotide probes specific for each mutation. The results showed that the
      prevalence of Hb CS and Hb Pakse in Central Thailand are 5.80 and 0.51%,
      respectively, which is in concordance with the results from previous studies.

PMID- 21077768
TI  - High-resolution melting analysis of the three common nondeletional alpha
      thalassemia mutations in the Chinese population: Hbs Constant Spring, Quong Sze
      and Westmead.
AB  - alpha-Thalassemia (alpha-thal) is one of the most common monogenic diseases
      worldwide and is widely distributed in southern China. There are two types of
      this disease at the DNA level: deletional and nondeletional alpha-thal. Hb
      Constant Spring [Hb CS, alpha142, Term->Gln (alpha2)
      (alpha(CS)alpha/alphaalpha)], Hb Quong Sze [Hb QS, alpha125(H8)Leu->Pro (alpha2)
      (alpha(QS)alpha/alphaalpha/)] and Hb Westmead [alpha122(H5)His->Gln (alpha2)
      (alpha(122)alpha/alphaalpha)] are the three common nondeletional mutations in the
      Chinese population. In this study, we developed an optimized protocol for
      identification of the three point mutations by high-resolution melting (HRM)
      analysis using a LightScanner. We successfully detected all the mutant samples
      with alpha(CS)alpha/alphaalpha, alpha(CS)alpha/- -(SEA), alpha(CS)alpha/
      alpha(3.7), alpha(CS)alpha/-alpha(4.2), alpha(QS)alpha/alphaalpha,
      alpha(QS)alpha/- -(SEA), alpha(QS)alpha/-alpha(4.2),
      alpha(QS)alpha/alpha(QS)alpha, and alpha(122)alpha/alphaalpha. High-resolution
      melting analysis is a time-saving and cost-effective technique, and the method
      established here could be applied to screen the three common point mutations,
      especially in individuals whose partners are a carrier of alpha0-thal.

PMID- 21077769
TI  - Identification of a novel delta-globin gene mutation in an Iranian family.
AB  - delta-Thalassemia (delta-thal) has no clinical symptoms, but its coinheritance
      with beta-thal may cause misdiagnosis, especially in countries with a high
      prevalence of beta-thal where prevention programs have been implemented. The
      molecular basis of most beta-thal syndromes have been defined, while the spectrum
      of mutations causing delta-thal have not been well characterized. A couple was
      referred to us for thalassemia molecular screening. Since she had rather low
      values of Hb A2 and normal Hb F, her delta-globin gene was amplified and directly
      sequenced. We found two different mutations on her delta-globin genes: HBD:
      c.92+5G>T/HBD:c.428C>A. The c.92+5G>T mutation has not been previously reported.
      Two different mutations in trans may explain the reduced Hb A2 level.

PMID- 21077770
TI  - A new beta-thalassemia deletion mutation [codon 36 (-C)] observed in a Chinese
      woman.
AB  - In this study we present the first report of the detection of a new beta
      thalassemia (beta-thal) mutation at codon 36 (-C) in the Chinese population. This
      frameshift mutation generates a TGA stop codon at position 60, resulting in a
      thalassemia phenotype. This is the first example of a premature stop codon at
      position 60 because of codon 36. The characterization of uncommon mutations is
      useful for the screening of beta-thal carriers, genetic counseling and prenatal
      diagnosis.

PMID- 21077771
TI  - Clinical and molecular characterization of beta(S) and
      (G)gamma((A)gammadeltabeta)0-thalassemia in eastern India.
AB  - Fetal hemoglobin (Hb F) is the most studied modifier of sickle cell disease.
      Coinheritance of high Hb F determinants such as deltabeta-thalassemia (deltabeta
      thal) and hereditary persistence of fetal hemoglobin (HPFH) can contribute to
      raised Hb F concentration in these patients. One hundred and seventy-six cases of
      sickle cell disease with high Hb F were screened for the presence of the Asian
      Indian deletion-inversion (G)gamma((A)gammadeltabeta)0-thal and HPFH-3 (Indian,
      48.5 kb) disorders. Three cases from two unrelated families were found to have
      sickle cell disease and the ((A)gammadeltabeta)0-thal genotype. Three other
      members had heterozygous (G)gamma((A)gammadeltabeta)0-thal. None had HPFH-3.
      Despite very high Hb F concentrations and linkage of the beta(S) gene to Asian
      haplotypes, the compound heterozygotes had severe clinical presentation, possibly
      because of heterocellular distribution of Hb F. In conclusion, these high Hb F
      determinants are not common causes of high Hb F in Indian sickle cell disease
      patients.

PMID- 21077772
TI  - An ABC transporter and a cytochrome P450 of Nectria haematococca MPVI are
      virulence factors on pea and are the major tolerance mechanisms to the
      phytoalexin pisatin.
AB  - The fungal plant pathogen Nectria haematococca MPVI produces a cytochrome P450
      that is responsible for detoxifying the phytoalexin pisatin, produced as a
      defense mechanism by its host, garden pea. In this study, we demonstrate that
      this fungus also produces a specific ATP-binding cassette (ABC) transporter,
      NhABC1, that enhances its tolerance to pisatin. In addition, although both
      mechanisms individually contribute to the tolerance of pisatin and act as host
      specific virulence factors, mutations in both genes render the fungus even more
      sensitive to pisatin and essentially nonpathogenic on pea. NhABC1 is rapidly
      induced after treatment with pisatin in vitro and during infection of pea plants.
      Furthermore, NhABC1 was able to confer tolerance to the phytoalexin rishitin,
      produced by potato. NhABC1 appears to be orthologous to GpABC1 of the potato
      pathogen Gibberella pulicaris and, along with MoABC1 from Magnaporthe oryzae,
      resides in a phylogenetically related clade enriched with ABC transorters
      involved in virulence. We propose that NhABC1 and the cytochrome P450 may
      function in a sequential manner in which the energy expense from pisatin efflux
      by NhABC1 releases the repression of the cytochrome P450, ultimately allowing
      pisatin tolerance by two mechanisms. These results demonstrate that a successful
      pathogen has evolved multiple mechanisms to overcome these plant antimicrobial
      compounds.

PMID- 21077773
TI  - Plants respond to pathogen infection by enhancing the antifungal gene expression
      of root-associated bacteria.
AB  - Plant health and fitness widely depend on interactions with soil microorganisms.
      Some bacteria such as pseudomonads can inhibit pathogens by producing
      antibiotics, and controlling these bacteria could help improve plant fitness. In
      the present study, we tested whether plants induce changes in the antifungal
      activity of root-associated bacteria as a response to root pathogens. We grew
      barley plants in a split-root system with one side of the root system challenged
      by the pathogen Pythium ultimum and the other side inoculated with the biocontrol
      strain Pseudomonas fluorescens CHA0. We used reporter genes to follow the
      expression of ribosomal RNA indicative of the metabolic state and of the gene
      phlA, required for production of 2,4-diacetylphloroglucinol, a key component of
      antifungal activity. Infection increased the expression of the antifungal gene
      phlA. No contact with the pathogen was required, indicating that barley
      influenced gene expression by the bacteria in a systemic way. This effect relied
      on increased exudation of diffusible molecules increasing phlA expression,
      suggesting that communication with rhizosphere bacteria is part of the pathogen
      response of plants. Tripartite interactions among plants, pathogens, and bacteria
      appear as a novel determinant of plant response to root pathogens.

PMID- 21077774
TI  - Genetic diversity and a PCR-based method for Xanthomonas axonopodis detection in
      passion fruit.
AB  - Xanthomonas axonopodis pv. passiflorae causes bacterial spot in passion fruit. It
      attacks the purple and yellow passion fruit as well as the sweet passion fruit.
      The diversity of 87 isolates of pv. passiflorae collected from across 22 fruit
      orchards in Brazil was evaluated using molecular profiles and statistical
      procedures, including an unweighted pair-group method with arithmetical averages
      based dendrogram, analysis of molecular variance (AMOVA), and an assigning test
      that provides information on genetic structure at the population level. Isolates
      from another eight pathovars were included in the molecular analyses and all were
      shown to have a distinct repetitive sequence-based polymerase chain reaction
      profile. Amplified fragment length polymorphism technique revealed considerable
      diversity among isolates of pv. passiflorae, and AMOVA showed that most of the
      variance (49.4%) was due to differences between localities. Cluster analysis
      revealed that most genotypic clusters were homogeneous and that variance was
      associated primarily with geographic origin. The disease adversely affects fruit
      production and may kill infected plants. A method for rapid diagnosis of the
      pathogen, even before the disease symptoms become evident, has value for
      producers. Here, a set of primers (Xapas) was designed by exploiting a single
      nucleotide polymorphism between the sequences of the intergenic 16S-23S rRNA
      spacer region of the pathovars. Xapas was shown to effectively detect all pv.
      passiflorae isolates and is recommended for disease diagnosis in passion fruit
      orchards.

PMID- 21077775
TI  - Relationship of five anthropometric indices and blood pressure in an adult
      Chinese population.
AB  - The study examined the relationship of blood pressure (BP) with anthropometric
      indices, including body mass index (BMI), waist-to-hip ratio (WHR), conicity
      index (CI), waist circumference (WC), and hip circumference (HC). The sample
      consisted of 731 females and 911 males aged 20-60 years randomly recruited from
      Shanxi Province of PR China. There was an increasing trend of systolic blood
      pressure (SBP), diastolic blood pressure (DBP), and the five anthropometric
      indices in successively older age groups. Except for female HC, all the other
      anthropometric indices were significantly correlated with BPS. Among them, WC and
      HC exhibited the highest correlations in female (0.38-0.42) and in male (0.36
      0.37), respectively. The result indicates that HC is not protective for metabolic
      risk factors in males. Principal component analysis (PCA) was performed on all
      the five anthropometric indices and four major principal components (PCs) were
      obtained to explain greater variances (R(2) = 0.173-0.212) in BPS than did anyone
      of five anthropometric indices (R(2) = 0.0001-0.176). The same analyses were
      conducted on any two, three, and four indices of the five anthropometric ones, in
      order to get the smaller and optimal sets of indices to estimate BPs. Our results
      suggest that BMI, WC, and HC are the smallest set of anthropometric indices to
      optimally estimate BP for the males, and WC and BMI for the females.

PMID- 21077776
TI  - Caerulein-induced acute pancreatitis results in mild lung inflammation and
      altered respiratory mechanics.
AB  - Acute lung injury is a common complication of acute pancreatitis (AP) and
      contributes to the majority of AP-associated deaths. Although some aspects of AP
      induced lung inflammation have been demonstrated, investigation of resultant
      changes in lung function is limited. The aim of this study was to characterize
      lung injury in caerulein-induced AP. Male Sprague Dawley rats (n = 7-8/group)
      received 7 injections of caerulein (50 MUg/kg) at 12, 24, 48, 72, 96, or 120
      hours before measurement of lung impedance mechanics. Bronchoalveolar lavage
      (BAL), plasma, pancreatic, and lung tissue were collected to determine pancreatic
      and lung measures of acute inflammation. AP developed between 12 and 24 hours, as
      indicated by increased plasma amylase activity and pancreatic myeloperoxidase
      (MPO) activity, edema, and abnormal acinar cells, before beginning to resolve by
      48 hours. In the lung, MPO activity peaked at 12 and 96 hours, with BAL cytokine
      concentrations peaking at 12 hours, followed by lung edema at 24 hours, and BAL
      cell count at 48 hours. Importantly, no significant changes in BAL protein
      concentration or arterial blood gas-pH levels were evident over the same period,
      and only modest changes were observed in respiratory mechanics. Caerulein-induced
      AP results in minor lung injury, which is not sufficient to allow protein
      permeability and substantially alter respiratory mechanics.

PMID- 21077777
TI  - L-Arginine-induced acute pancreatitis results in mild lung inflammation without
      altered respiratory mechanics.
AB  - Acute lung injury is a common complication of acute pancreatitis (AP) and
      contributes to the majority of AP-associated deaths. Although some aspects of AP
      induced lung inflammation have been demonstrated, investigation of resultant
      changes in lung function is limited. The aim of this study was to characterize
      acute lung injury in L-arginine-induced AP. Seven groups of male Sprague-Dawley
      rats (n = 4-10/group) received 2 intraperitoneal (i.p.) injections of L-arginine
      (250 mg/100 g) at 6, 12, 24, 36, 48, or 72 hours before measurement of lung
      impedance mechanics. Control rats (n = 10) received i.p. saline. Bronchoalveolar
      lavage (BAL), plasma, and pancreatic and lung tissue were collected to determine
      pancreatic and lung measures of acute inflammation. AP developed between 6 and 36
      hours, as indicated by increased pancreatic abnormal acinar cells,
      myeloperoxidase (MPO) activity, edema, and plasma amylase activity, before
      beginning to resolve by 72 hours. In the lung, MPO activity increased (2.4-fold)
      from 12 hours, followed by a modest increase in lung edema at 48 hours, with
      increased BAL cell count (2.5-fold) up to 72 hours (P < .05). In contrast, no
      significant changes in lung mechanics were evident over the same period. Despite
      measurable lung inflammation, no significant deterioration in respiratory
      function resulted from L-arginine-induced AP.

PMID- 21077778
TI  - The protective effect of overexpression of extracellular superoxide dismutase on
      nitric oxide bioavailability in the lung after exposure to hyperoxia stress.
AB  - The objective of this study was to determine whether overexpression of human
      extracellular superoxide dismutase (hEC-SOD) can preserve nitric oxide (NO)
      bioavailability. In vitro studies examined the transient expression of hEC-SOD in
      mouse epithelial (C10) cells and its effect on extracellular accumulation of NO,
      intracellular cyclic guanosine monophosphate (cGMP), and nuclear factor kappa B
      (NF-kappaB) activation under normal and oxidative stress conditions. In vivo,
      newborn rabbits were treated with a plasmid containing hEC-SOD cDNA or vehicle
      plasmid alone, followed by exposure to hyperoxia (Fio2 = 95% for 7 days). A third
      group was raised under normoxic conditions. cGMP and NF-kappaB activation were
      studied. There was significantly higher NO accumulation in cells expressing hEC
      SOD exposed to oxidative stress compared with nontransfected cells. Accumulation
      of cGMP was significantly higher in cells expressing hEC-SOD. Oxidative stress
      induced NF-kappaB activation, which was abrogated by hEC-SOD expression. In vivo,
      there was significantly higher cGMP accumulation in transfected neonatal rabbit
      lung tissue at 3 and 7 days of hyperoxic exposure. Immunostaining for NF-kappaB,
      showed a marked increase in NF-kappaB concentration in nontreated neonatal rabbit
      lung tissue compared to transfected neonatal lung with hEC-SOD and the control
      air group. These results show that transient EC-SOD overexpression maintains NO
      bioavailability, which directly leads to maintenance of cGMP activity and
      reduction of NF-kappaB activation under oxidative stress.

PMID- 21077779
TI  - Safety of sapropterin dihydrochloride (6r-bh4) in patients with pulmonary
      hypertension.
AB  - The authors investigated the safety of oral tetrahydrobiopterin (BH4), a cofactor
      for nitric oxide synthesis, as a novel treatment for pulmonary hypertension (PH).
      Eighteen patients with pulmonary arterial hypertension or inoperable chronic
      thromboembolic PH received sapropterin dihydrochloride (6R-BH4), the optically
      active form of BH4, in addition to treatment with sildenafil and/or endothelin
      receptor antagonists in an open-label, dose-escalation study. 6R-BH4 was
      administered starting at a dose of 2.5 mg/kg and increasing to 20 mg/kg over 8
      weeks. Changes in markers of nitric oxide synthesis, inflammation and oxidant
      stress, as well as exercise capacity and cardiac function were measured. 6R-BH4
      was well tolerated at all doses without systemic hypotension, even when given in
      combination with sildenafil. There was a small but significant reduction in
      plasma monocyte chemoattractant protein (MCP)-1 levels on 5 mg/kg. No significant
      changes in measures of nitric oxide synthesis or oxidant stress were observed.
      There was improvement in 6-minute walk distance, most significant at a dose of 5
      mg/kg, from 379 +/- 61 to 413 +/- 57 m 414 +/- 57 m (P = .002). Oral 6R-BH4 can
      be administered safely in doses up to 20 mg/kg daily to patients with PH. Further
      studies are needed to explore its therapeutic potential.

PMID- 21077780
TI  - Pulmonary effects of positive end-expiratory pressure and fluid therapy in
      experimental lung injury.
AB  - The separate effects of positive end-expiratory pressure (PEEP) and intravascular
      volume administration on the histopathologic lung injury were not investigated in
      experimental lung injury previously. The authors hypothesized that high PEEP and
      a restrictive volume therapy would yield the best oxygenation and the least
      degree of lung injury. Pigs (52.8 +/- 3.4 kg) underwent saline lavage-induced
      lung injury. The animals were ventilated either with low PEEP (mean PEEP 9 to 12
      cm H2O) and liberal volume therapy using hydroxyethyl starch (LowP/Vol+) or high
      PEEP (mean PEEP 21 cm H2O) combined with recruitment maneuvers and liberal
      (HighP/Vol+) or restrictive volume therapy (HighP/Vol-). After 6.5 hours, lung
      injury was determined by using a histopathologic score evaluating overdistension,
      edema, exsudation, and inflammation. When volume therapy was liberal, high PEEP
      (HighP/Vol+) improved the Pao2/Fio2 index (416 +/- 80 mm Hg) compared to low PEEP
      (LowP/Vol+, 189 +/- 55 mm Hg; P < .05) but there was no difference in the median
      (interquartile range) lung injury score: 1.6 (1.2-1.9) and 1.9 (1.4-2.0). High
      PEEP with restrictive volume therapy (HighP/Vol-) did not further improve
      oxygenation (400 +/- 55 mm Hg) but ameliorated the degree of lung injury: 0.9
      (0.8-1.4) (P < .05). In lavage-induced lung injury, high PEEP improved
      oxygenation, but restrictive volume administration markedly reduced the lung
      injury score, mainly by reduced edema.

PMID- 21077781
TI  - Lung fluid absorption is induced in preterm guinea pigs ventilated with low tidal
      volumes.
AB  - The objective of this study was to determine if low tidal volume (V(t))
      ventilation was beneficial when ventilating preterm fetuses. The authors
      ventilated preterm guinea pig fetuses at gestation day (GD) 67, 3 days before
      birth, newborn, and 10-day-old (PD10) guinea pigs with low V(t) (6 mL/kg body
      weight [bw]) and compared them to age-matched fetuses/animals ventilated with
      higher potentially injurious V(t) (12 mL/kg bw). Lung fluid absorption was
      measured after intratracheal instillation of 5% albumin in 0.9% NaCl. Low V(t)
      ventilation stimulated lung fluid absorption when compared to higher V(t) in all
      groups. The increased lung fluid absorption in low V(t)-ventilated fetuses was
      associated with increased alpha epithelial Na channel (alphaEnaC) mRNA. However,
      alphaENaC and betaENaC protein was unchanged over the 1-hour study. Because
      stretch induces mitogen-activated protein (MAP) kinase expression and MAP kinases
      may affect lung fluid absorption, the authors investigated if MAP kinase (MAPK)
      expression was affected by V(t). Extracellular signal-regulated kinase (ERK) and
      MAPK/ERK kinase (MEK) were phosphorylated in the higher V(t)-ventilated guinea
      pig fetuses. This suggested that a reduced activation of MAP kinases might
      explain the increased lung fluid absorption in the low V(t)-ventilated fetuses.
      Thus these data suggest that low V(t) ventilation increases fetal lung fluid
      absorption and thus may be preferential to use clinically.

PMID- 21077782
TI  - Effect atorvastatin on serum tumor necrosis factor alpha and interleukin-1beta
      following acute pulmonary embolism.
AB  - This study was designed to investigate the effect of atorvastatin on the serum
      levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) following acute pulmonary embolism (PE). Forty New Zealand white rabbits
      were divided into control and atorvastatin groups. Acute PE was created by
      injection of autologous blood clots into the femoral vein. Enzyme-linked
      immunosorbent assay was used to measure TNF-alpha and IL-1beta. At baseline,
      there was no significant difference in serum TNF-alpha (10.6 +/- 1.3 versus 11.2
      +/- 1.9 pg/mL; P > .05) or IL-1beta (8.2 +/- 1.0 versus 8.6 +/- 0.9 pg/mL; P >
      .05) between the control group and the atorvastatin group. In both groups, there
      was a significant increase in the serum TNF-alpha and IL-1beta following acute
      PE. However, the levels of serum TNF-alpha and IL-1beta in the atorvastatin group
      was significantly lower than in the control group following PE (P < .01). The
      authors conclude that acute PE is associated with a significant increase in serum
      proinflammatory factors TNF-alpha and IL-1beta. Pretreatment with atorvastatin
      diminished the increase in TNF-alpha and IL-1beta.

PMID- 21077783
TI  - Effect of maternal nicotine exposure on neonatal rat lung development: protective
      effect of maternal ascorbic acid supplementation.
AB  - In previous studies it was shown that maternal nicotine exposure during pregnancy
      and lactation interfered with fetal and neonatal lung growth and development. It
      was suggested that the adverse effects of maternal nicotine exposure on the lungs
      of the offspring may be due to inadequate protection of these lungs against
      oxidants. Wistar rats were used in this study. After mating the rats were
      randomly assigned into 4 groups, namely a control group, a group receiving only
      nicotine, a group exposed to only vitamin C, and a group exposed to both nicotine
      and vitamin C. The aim of this study was, firstly, to determine the effect of
      maternal nicotine exposure (1 mg/kg body weight/day, subcutaneously) during
      gestation and lactation on the lungs of the offspring; secondly, to test whether
      the subcutaneous administration of vitamin C (0.5 mg/kg body weight/day)
      influences lung development; and, lastly, to determine whether subcutaneous
      administration of vitamin C will prevent the adverse effects of maternal nicotine
      exposure on lung development in the offspring. Morphologic and morphometric
      techniques were used to determine the effect of nicotine and vitamin C on lung
      development in the offspring on postnatal days 14, 21, and 42. The results showed
      that maternal exposure to nicotine only or vitamin C only resulted in a gradual
      deterioration of the parenchyma of the lungs of the offspring. These changes,
      which resembled microscopic emphysema, only became evident after the lungs of the
      offspring reached maturation. Those animals that were exposed to both nicotine
      and vitamin C via the placenta and mother's milk were less severely affected. It
      is also not advisable to use subcutaneous administration of vitamin C during
      gestation and lactation to prevent smoke- and nicotine-related effects on the
      developing lung, and other strategies should be investigated.

PMID- 21077784
TI  - Pharmacokinetic evaluation of etravirine.
AB  - IMPORTANCE OF THE FIELD: successful long-term treatment of HIV is hindered by
      development of resistance and providing active regimens for treatment-experienced
      patients remains challenging. Development of antiretrovirals active against
      resistant virus, such as the diarylpyrimidine non-nucleoside reverse
      transcriptase inhibitor (NNRTI) etravirine, is important to broaden treatment
      options to patients who have few available. AREAS COVERED IN THIS REVIEW: we
      summarise pharmacology, pharmacokinetics, drug-drug interactions and clinical
      data of etravirine based on a PubMed search between 01 January 2003 and 01
      September 2010 as well as relevant information from conference proceedings and
      the latest Summary of Product Characteristics and US Prescribing Information.
      WHAT THE READER WILL GAIN: the reader will gain a comprehensive overview of
      etravirine clinical pharmacology, drug-drug interactions and mechanism of action.
      Information regarding efficacy, safety and tolerability in specific patients
      groups is provided to allow the reader to form an opinion regarding the role of
      etravirine in clinical practice. TAKE HOME MESSAGE: etravirine, along with other
      new antiretrovirals, has widened treatment options for patients with multi-drug
      resistance. Etravirine is well tolerated with the majority of drug-drug
      interactions manageable and is effective in triple-class experienced patients.
      Clinical studies investigating etravirine in treatment-naive patients are ongoing
      to further clarify its safety and resistance profile.

PMID- 21077785
TI  - Pharmacokinetic evaluation of continuous intravenous epoprostenol.
AB  - IMPORTANCE OF THE FIELD: prostacyclin is the main arachidonic acid metabolite and
      its decrease has been proven to be important in the pathophysiology of the
      pulmonary arterial hypertension (PAH). Epoprostenol has been the first analog of
      prostacyclin to be approved for the treatment of PAH and despite the development
      of therapeutic options, the last recommendations of European Societies of
      Cardiology and Pulmonology maintain it as the first choice therapy for severe
      patients in the WHO functional class IV. In this review, we focus on
      pharmacokinetics of epoprostenol characterized by its instability in aqueous
      biological fluids and compare its pharmacokinetics with other stable analogs of
      prostacyclin. Moreover, pharmacodynamics, clinical efficacy and safety of
      epoprostenol were studied. AREAS COVERED IN THIS REVIEW: a literature search and
      review of the studies published on epoprostenol were carried out using the
      MEDLINE database. WHAT THE READER WILL GAIN: the paper provides the reader with
      information on epoprostenol pharmacokinetics and comparison with other analogs of
      prostacyclin. This paper also provides data on pharmacodynamics, clinical
      efficacy, safety and tolerability of epoprostenol. TAKE HOME MESSAGE: despite
      epoprostenol's short half-life and complicated delivery system, this treatment
      remains the first choice therapy for severe PAH patients.

PMID- 21077786
TI  - Symptomatic improvement after catheter ablation of supraventricular tachycardia
      measured by the arrhythmia-specific questionnaire U22.
AB  - INTRODUCTION: The main indication for ablation of supraventricular tachycardia is
      symptomatic relief. Generic measures of quality of life are not suitable for
      direct evaluation of arrhythmia-related symptoms, and a specific tool is needed.
      The questionnaire U22 quantifies symptoms associated with arrhythmic events. It
      uses discrete 0-10 scales for quantification of influence of arrhythmia on well
      being, intensity of discomfort, type of dominant symptom, and a time aspect that
      summarizes duration and frequency of spells. We evaluated U22 in a well defined
      group of patients with paroxysmal supraventricular tachycardia, undergoing an
      intervention with a distinct end-point and a high success rate. METHODS: Symptoms
      in patients with accessory pathway and atrioventricular nodal re-entrant
      tachycardia scheduled for ablation were measured with U22 and SF-36 on admission.
      The evaluation was repeated after 6 months. RESULTS: Altogether 58 patients
      successfully ablated in 2006-2008 completed the four forms (U22 and SF-36 at base
      line and follow-up, 210 +/- 35 days after ablation). The score for well-being (0
      10; 10 being best) increased from 5.9 +/- 2.6 to 7.9 +/- 1.9 (P < 0.0005). The
      score for arrhythmia as cause for impairment in well-being (0-10; 10 being
      highest) decreased from 7.5 +/- 2.8 to 2.0 +/- 3.1 (P < 0.0005). The time aspect
      score (0-10) decreased from 4.7 +/- 1.5 to 1.4 +/- 1.8 (P < 0.0005). The two SF
      36 summary measures PCS and MCS increased from 46.9 +/- 9.4 to 48.4 +/- 10.7 and
      from 44.9 +/- 12.5 to 49.1 +/- 9.9 (P = 0.04 and 0.002). CONCLUSION: After
      successful ablation of accessory pathway and atrioventricular nodal re-entrant
      tachycardia, the U22 protocol detected a relevant increase in arrhythmia-related
      well-being. Modest improvement in general well-being was detected by the SF-36
      protocol.

PMID- 21077788
TI  - An appraisal of the published literature on the safety and toxicity of food
      related nanomaterials.
AB  - Nanotechnology is poised to impact the food and food-related industries through
      improvements in areas as diverse as production, packaging, shelf life, and
      bioavailability of food and beverage components. An evaluation was undertaken to
      characterize the published literature pertaining to the safety of oral exposure
      to food-related nanomaterials and to identify research needs in this area. Thirty
      publications were identified in which a toxicological endpoint was assessed
      following in vivo (oral) or in vitro exposure to food-related nanomaterials.
      These publications were evaluated for overall quality using a two-step method
      that determined the reliability of the study design and the extent of
      nanomaterial characterization within each study. Of the 21 in vivo studies
      evaluated, 20 used mice or rats, 15 were lacking in some critical component of
      study design (e.g., oral gavage dose volume was not reported), none was longer
      than 90 days in duration, and only seven reported more than five physicochemical
      parameters for the nanomaterial(s) being evaluated. Of the nine in vitro studies
      evaluated, seven focused on cytotoxicity, two evaluated genotoxicity, only five
      reported more than five physicochemical parameters for the nanomaterial(s) being
      evaluated, and none discussed the potential interference by the nanomaterial(s)
      of the experimental assays that were employed. The results of this evaluation
      indicate that there is currently insufficient reliable data to allow clear
      assessment of the safety of oral exposure to food-related nanomaterials.
      Significant investment must be made to generate studies of sufficient quality and
      duration and that report comprehensive nanomaterial characterization such that
      results can be judged reliable and interpretable. Failure to do so will result in
      the perpetuation of the publication of studies that are inadequate for use in
      risk characterization.

PMID- 21077789
TI  - Determinants of circulating asymmetric and symmetric dimethylarginines in
      patients evaluated for acute dyspnea.
AB  - BACKGROUND: The relationship between asymmetric dimethylarginine (ADMA) and
      symmetric dimethylarginine (SDMA) plasma concentrations and acute heart failure
      is unknown. We evaluated ADMA and SDMA in patients with acute dyspnea. METHODS:
      We studied 57 dyspneic subjects (50-95 years), with estimated glomerular
      filtration rate (eGFR) >= 30 mL/min/1.73 m2, presenting to the emergency
      department. Troponin I, N terminal-proBNP (NT-proBNP), ADMA, and SDMA were
      measured. Electrocardiogram, chest X-ray and lung ultrasound were performed.
      Patients were classified into cardiogenic dyspnea and non-cardiogenic dyspnea,
      and were also classified on the basis of renal function according to their eGFR.
      RESULTS: Two-way analysis of variance demonstrated that ADMA and SDMA did not
      differ for type of dyspnea, but increased in renal dysfunction. NT-proBNP
      significantly increased both in cardiogenic dyspnea and renal dysfunction.
      Multiple regression analysis demonstrated that after adjustment for troponin and
      dyspnea, the only variables which significantly correlated with SDMA plasma
      concentrations were renal function (beta = -0.47, p < 0.001) and NT-proBNP (beta
      = 0.28, p = 0.02). CONCLUSIONS: Neither type of dimethylarginine showed
      cardiogenic dyspnea to be a determinant for plasma concentrations. Renal
      dysfunction was a confounder for both ADMA and SDMA.

PMID- 21077790
TI  - Stability of serum samples and hemolysis interference on the high sensitivity
      troponin T assay.

PMID- 21077792
TI  - Hypercoagulable state, pathophysiology, classification and epidemiology.
AB  - Hypercoagulable state is not a uniform disease. It is a complex condition with an
      abnormal propensity for thrombosis that may or may not lead to thrombosis,
      depending on complex gene-gene and gene-environment interactions. The prevalence
      of the hypercoagulable state depends on the ethnicity and clinical history of the
      population being studied. The consequences of a hypercoagulable state due to
      thrombosis of veins and arteries are the most important cause of sickness and
      death in developed countries at present. Primary hypercoagulable state is an
      inherited condition caused by the reduced level of natural anticoagulants due to
      a qualitative defect or quantitative deficiency of an antithrombotic protein, or
      increased concentrations or function of coagulation factors. Most of the
      inherited abnormalities recognized to date have little or no effect on arterial
      thrombosis and are associated primarily with venous thromboembolism. Arterial
      thrombosis usually develops as a complication of atherosclerosis and patients
      usually have more than one traditional risk factor. Secondary hypercoagulable
      states generally occur as a result of a large number of transient or permanent
      acquired conditions that increase the tendency for formation of blood clots. New
      epidemiological data and clinical trials suggest that many acquired risk factors
      in the pathophysiology of arterial and venous thrombosis overlap and coexist for
      both disorders.

PMID- 21077791
TI  - A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung
      phenotype in F508del homozygous Italian cystic fibrosis patients.
AB  - BACKGROUND: The identification of cystic fibrosis (CF) patients who are at
      greater risk of lung damage could be clinically valuable. Thus, we attempted to
      replicate previous findings and verify the possible association between three
      single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5'
      untranslated region (5' UTR) of the beta defensin 1 (DEFB1) gene and the CF
      pulmonary phenotype. METHODS: Genomic DNA from 92 Italian CF patients enrolled in
      different regional CF centres was extracted from peripheral blood and genotyped
      for DEFB1 SNPs using TaqMan((r)) allele specific probes. In order to avoid
      genetic confounding causes that can account for CF phenotype variability, all
      patients were homozygous for the F508del CFTR mutation, and were then classified
      on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or
      severe lung phenotype patients (Sp, n=42). RESULTS: For the c.-20G>A SNP, the
      frequency of the A allele, as well as the AA genotype, were significantly more
      frequent in Mp than in Sp patients, and thus this was associated with a
      protective effect against severe pulmonary disease (OR=0.48 and 0.28,
      respectively). The effect of the c.-20G>A A allele is consistent with a recessive
      model, and the protective effect against Sp is exerted only when it is present in
      homozygosis. For the other two SNPs, no differences were observed as allelic and
      genotypic frequency in the two subgroups of CF patients. CONCLUSIONS: Our
      results, although necessary to be confirmed in larger and multiethnic
      populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary
      phenotype.

PMID- 21077793
TI  - Serum zinc-alpha2-glycoprotein concentrations in patients with non-alcoholic
      fatty liver disease.
AB  - BACKGROUND: Evidence suggests that zinc-alpha(2)-glycoprotein (ZAG) might serve
      as a biomarker for human metabolic alterations. We measured serum ZAG in patients
      with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the
      metabolic syndrome, and examined its association with clinical, biochemical, and
      histological phenotypes. METHODS: Serum ZAG was determined using ELISA in 90
      patients with biopsy-proven NAFLD and 81 controls. RESULTS: Serum ZAG
      concentrations did not differ in patients with NAFLD (median 61 MUg/mL;
      interquartile range: 56-73 MUg/mL) compared with healthy controls (median 66
      MUg/mL; interquartile range: 56-78 MUg/mL, Mann-Whitney U-test, p=NS). However,
      among patients with NAFLD serum ZAG concentrations were significantly higher in
      males and in those with the metabolic syndrome. After stepwise linear regression
      analysis, serum ZAG concentrations were the only independent predictor of the
      number of metabolic syndrome components in patients with NAFLD (beta=0.22;
      t=2.001, p<0.05). CONCLUSIONS: In summary, the hypothesis of an association
      between NAFLD and serum ZAG concentrations is not supported by the present
      results. However, ZAG remains an interesting molecule for further research in the
      field of human metabolic disorders.

PMID- 21077794
TI  - Hepcidin: the main regulator of iron homeostasis.

PMID- 21077795
TI  - Bilateral pinna chondritis preceded by glucosamine chondroitin supplement
      initiation.

PMID- 21077796
TI  - Introducing the new editor of amyloid: the journal of protein folding disorders,
      Per Westermark, M.D., Ph.D.

PMID- 21077797
TI  - Transthyretin-related vitreous amyloidosis in different endemic areas.
AB  - BACKGROUND: to investigate the vitreous opacity in patients with familial
      amyloidotic polyneuropathy (FAP) in two major endemic areas, Japan and Sweden.
      METHODS: we obtained clinical data for 90 patients with vitreous opacity that was
      associated with FAP amyloidogenic transthyretin (ATTR) Val30Met; 18 Japanese
      patients and 72 Swedish patients. We reviewed medical records at Kumamoto
      University Hospital in Japan and Umea University Hospital in Sweden. We evaluated
      the characteristics of the patients, systemic and ocular histories, clinical
      findings and treatment. RESULTS: swedish patients were significantly older at the
      onset of vitreous opacity (mean age 67.8 years) than were Japanese patients (47.6
      years). A similar age difference was found for the onset of polyneuropathy. In
      addition, Swedish patients without polyneuropathy were significantly older (74.1
      years) at the onset of vitreous opacity than those with polyneuropathy (64.6
      years). A significant difference in the occurrence of vitreous opacity as the
      only manifestation of FAP was seen for Swedish patients (35%) compared with
      Japanese patients (6%). CONCLUSIONS: swedish FAP ATTR Val30Met patients appeared
      to develop vitreous opacity later and more frequently compared with Japanese
      patients.

PMID- 21077798
TI  - Comparison of amyloid fibril formation by two closely related immunoglobulin
      light chain variable domains.
AB  - Light chain amyloidosis (AL amyloidosis) is a haematological disorder in which a
      clonal population of B cells expands and secretes enormous amounts of the
      immunoglobulin light chain protein. These light chains misfold and aggregate into
      amyloid fibrils, leading to organ dysfunction and death. We have studied the in
      vitro fibril formation kinetics of two patient-derived immunoglobulin light chain
      variable domain proteins, designated AL-09 and AL-103, in response to changes in
      solution conditions. Both proteins are members of the kappaI O18:O8 germline and
      therefore are highly similar in sequence, but they presented with different
      clinical phenotypes. We find that AL-09 forms fibrils more readily and more
      rapidly than AL-103 in vitro, mirroring the clinical phenotypes of the patients
      and suggesting a possible connection between the fibril kinetics of the disease
      protein and the disease progression.

PMID- 21077800
TI  - Gustatory and olfactory function in rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate the gustatory and olfactory functions of patients with
      rheumatoid arthritis (RA) compared to sex- and age-matched healthy subjects and
      to investigate a potential relationship between disease activity [using the 28
      joint Disease Activity Score (DAS28)] and chemosensory capacity. Furthermore, to
      dissect possible impacts of standard anti-inflammatory medications on the
      gustatory and olfactory functions. METHODS: Patients with established RA
      underwent standardized assessment of their gustatory and olfactory functions. The
      patients were also examined for their disease activity, had their specific blood
      test results analysed, and were asked to answer a standardized questionnaire
      about their quality of life, the negative effects of their disease, and about
      comorbidities. RESULTS: A total of 101 RA patients (75 women, 26 men, mean age:
      57.9 +/- 13.8 and 64.2 +/- 10.9 years, respectively) were analysed. In relation
      to age- and sex-related subjects, both female and male RA patients had a
      significantly decreased taste score (p < 0.001) and also a significantly
      decreased olfactory score (p < 0.05), indicating that a substantial number of
      patients suffer from hypogeusia or hyposmia. This abnormality did not correlate
      with disease activity, the duration of the disease, disease-modifying anti
      rheumatic drug (DMARD) or tumour necrosis factor (TNF) inhibitor use, and the
      loss of the chemosensory functions, together indicating that hypogeusia and
      hyposmia are frequent clinical manifestations in RA patients independent of the
      inflammatory activity of their disease. CONCLUSION: The results indicate that
      there is a significant decrease in the olfactory and gustatory function in RA
      patients compared to those of healthy controls, which can seriously and
      substantially affect the quality of the patients' life.

PMID- 21077799
TI  - A bilateral cicatricial ectropion and bilateral upper lid shortening caused by 5
      fluorouracil toxicity in a patient with dihydropyrimidine dehydrogenase
      deficiency.
AB  - CONTEXT: Well-known causes of a cicatrizing ectropion are chemical/thermal
      injuries, dermatitis, cutaneous diseases, malignancies, and trauma. We add to
      this preceding list a systemic cause of a cicatrizing ectropion as a result of a
      rare side effect of 5-fluorouracil (5-FU), a common and frequently used
      chemotherapeutic agent. METHODS: A case report demonstrating the clinical
      presentation of a cicatricial ectropion caused by (5-FU) chemotherapy toxicity in
      a patient with dihydropyrimidine dehydrogenase deficiency. We also describe the
      subsequent investigations and management of this case. RESULTS: A bilateral
      cicatrizing lower lid ectropion, bilateral upper lid shortening, cicatrizing and
      sclerosing facial skin changes occurred in an 80-year-old male, undergoing
      preoperative chemoradiotherapy, incorporating Capecitabine, an oral 5-FU prodrug
      for a locally advanced rectal carcinoma. Severe 5-FU toxicity ultimately proved
      fatal but in addition to typical 5-FU related adverse effects, the patient
      developed bilateral incomplete lid closure, secondary corneal exposure and
      keratopathy. Due to the patient's extreme ill health, he was managed
      conservatively with a moist chamber. CONCLUSION: 5-fluorouracil chemotherapy in
      patients with dihydropyrimidine dehydrogenase deficiency, can give rise to ocular
      and cutaneous toxicity. We also present the complex management problems that have
      to be anticipated in treating such systemically compromised patients.

PMID- 21077801
TI  - Treatment with low-dose prednisolone is associated with altered body composition
      but no difference in bone mineral density in rheumatoid arthritis patients: a
      controlled cross-sectional study.
AB  - OBJECTIVES: To determine whether low-dose prednisolone affects body composition
      and bone mineral density (BMD) in patients with rheumatoid arthritis (RA), also
      considering inflammation and physical disability. METHODS: This cross-sectional
      study included 100 patients (50 women) with RA with a median (IQR) disease
      duration of 8 (4-15) years. Fifty patients had been treated with prednisolone (5
      7.5 mg) for at least 2 years (the P-group) and 50 patients matched for gender and
      age had not (the NoP-group). Body composition and BMD were assessed by dual
      energy X-ray absorptiometry (DXA). Disease activity (28-joint Disease Activity
      Score, DAS28) and physical disability (Health Assessment Questionnaire, HAQ) were
      assessed. RESULTS: The total patient group had increased fat mass (FM) and a high
      trunk:peripheral fat ratio, of which 38% had a fat free mass index (FFMI, kg/m2)
      below the 10th percentile of a reference population. The P-group had
      significantly higher FM but similar lean body mass (LBM) and BMD compared with
      the NoP-group. In multivariate analyses, treatment with prednisolone and a higher
      HAQ score were significantly and independently associated with higher FM but not
      with LBM. Higher C-reactive protein (CRP) was independently associated with lower
      LBM. Higher HAQ score and low weight were significantly and independently
      associated with lower BMD at femoral neck and lumbar spine. CONCLUSIONS: RA
      patients treated with low-dose prednisolone had significantly higher FM than
      patients without prednisolone, an effect that was independent of current
      inflammation. However, there was no association between prednisolone treatment
      and muscle mass or BMD. Thus, the net effect of prednisolone on body composition
      and bone is different in inflammatory diseases such as RA.

PMID- 21077802
TI  - Post-radiation scleredema adultorum and diffuse eosinophilic fasciitis in the
      same patient.

PMID- 21077803
TI  - Inhibition effects of the classical pathway complement of three Sorghum bicolor
      from South Korea.
AB  - The present study evaluated the anti-complement effects from organic solvent
      extracts of three varieties (Hwanggeumchal Sorghum, Chal Sorghum, and Heuin
      Sorghum) from Sorghum bicolor in classical pathway complement system. We have
      evaluated organic solvent extract from Sorghum bicolor varieties with regard to
      its anti-complement activity. Chal Sorghum ethyl acetate extract showed
      inhibitory activity against complement system with 50% inhibitory concentrations
      (IC(50)) values of 38.7 MUg/mL. This is the first report of anti-complement
      activity from Sorghum bicolor varieties.

PMID- 21077804
TI  - Major essential oils composition and immunotoxicity activity from leaves of
      Foeniculum vulgare against Aedes aegypti L.
AB  - The leaves of Foeniculum vulgare (Umbelliferae) were extracted and the major
      essential oil composition and immunotoxicity effects were studied. The analyses
      conducted by gas chromatography and mass spectroscopy (GC-MS) revealed the
      essential oils of F. vulgare leaves. The F. vulgare essential oil yield was
      0.97%, and GC/MS analysis revealed that its major constituents were methyl
      clavicol (46.3%), alpha-phellandrene (18.2%), fenchone (10.6%), (E)-anethole
      (11.3%), myrcene (3.4%), and alpha-pinene (2.1%). The essential oil had a
      significant toxic effect against early fourth-stage larvae of Aedes aegypti L
      with an LC(50) value of 41.23 ppm and an LC(90) value of 65.24 ppm. Also, methyl
      clavicol (>=98.0%), alpha-phellandrene (>=95.0%), fenchone (>=98.0%), (E)
      anethole (>=99.0%), myrcene (>=99.0%), and alpha-pinene (>=99.0%) were tested
      against the F(21) laboratory strain of A. aegypti. Fenchone (>=98.0%) and (E)
      anethole (>=99.0%) have medium activity with an LC(50) value of 73.11 ppm and
      102.41 ppm. The above data indicate that major compounds interaction may play a
      more important role in the toxicity of essential oil.

PMID- 21077807
TI  - About plasma arginin vasopressin levels and Meniere's disease.

PMID- 21077806
TI  - ALSUntangled No. 7: Investigating hyperimmune goat serum (Aimspro) for ALS.
AB  - The mechanism of Aimspro remains unproven; if it is an immunomodulator and/or a
      modulator of sodium channels, it theoretically could be useful in ALS. A single,
      detailed but significantly flawed case report documents slowing in decline of
      certain respiratory functions in a patient claiming to have ALS, who started
      Aimspro shortly after bipap. Based upon this limited information, ALSUntangled
      supports further study of Aimspro, either in ALS animal models or in a small
      phase 2 trial with clear and objective endpoints carried out by skilled trialists
      familiar with the problems inherent with ALS clinical studies. Until a trial is
      undertaken, however, we do not support further use of this product by PALS.

PMID- 21077809
TI  - The Australian Medical Council: beyond the first 25 years.

PMID- 21077810
TI  - Lowering Australia's defence against infectious diseases.

PMID- 21077811
TI  - Are you listening? The inaugural Australian Otitis Media (OMOZ) workshop--towards
      a better understanding of otitis media.

PMID- 21077812
TI  - Symptoms, investigations and management of patients with cancer of the oesophagus
      and gastro-oesophageal junction in Australia.
AB  - OBJECTIVE: To document presenting symptoms, investigations and management for
      Australian patients with oesophageal adenocarcinoma (OAC), gastro-oesophageal
      junction adenocarcinoma (GOJAC) and oesophageal squamous cell carcinoma (OSCC).
      DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of a population-based
      sample of 1100 Australian patients aged 18-79 years with histologically confirmed
      oesophageal cancer diagnosed in 2002-2005, using data from cancer registries and
      treatment centres, supplemented with clinical information collected through
      medical record review in 2006-2007 and mortality information collected in 2008.
      MAIN OUTCOME MEASURES: Prevalence of primary symptoms, and staging investigations
      and treatment modalities used. RESULTS: The primary presenting symptom was
      dysphagia, which was self-reported by 41%, 39% and 48% of patients with OAC,
      GOJAC and OSCC, respectively. Less common symptoms were reflux, chest pain,
      bleeding and weight loss. All patients underwent endoscopy, most had a staging
      computed tomography scan (OAC 93%, GOJAC 95% and OSCC 93%), and about half had
      positron emission tomography scans (OAC 51%, GOJAC 44% and OSCC 42%).
      Pretreatment tumour stage was reported in 25% of records, and could be derived
      from results of investigations in a further 23%, but the remaining half lacked
      sufficient information to ascribe a pretreatment stage. Curative treatments were
      attempted for 60% of OAC, 88% of GOJAC and 65% of OSCC patients. Surgery was
      performed on 52% of OAC, 83% of GOJAC and 41% of OSCC patients. About two-thirds
      of surgical patients received additional therapies. CONCLUSIONS: With anticipated
      increases in oesophageal cancer incidence, the resources required to diagnose and
      manage patients with oesphageal cancer are also likely to rise. Our data provide
      a baseline from which to plan for the future care of patients with cancers of the
      oesophagus.

PMID- 21077813
TI  - Perceived practice change in Australian doctors as a result of medicolegal
      concerns.
AB  - OBJECTIVES: To explore the perceived impact of medicolegal concerns on how
      Australian doctors practise medicine and to compare doctors who have experienced
      a medicolegal matter with those who have not. DESIGN AND SETTING: Cross-sectional
      survey (posted in September 2007, with reminder 4 weeks later) of Australian
      doctors from all major specialty groups, trainees and a sample of general
      practitioners who were insured with a medical insurance company. PARTICIPANTS:
      2999 respondents of 8360 who were sent the survey. MAIN OUTCOME MEASURES:
      Perceived practice changes due to concerns about medicolegal issues, beliefs
      about medicolegal issues, and the influence of medicolegal issues on both career
      choices and how doctors relate to their patients. RESULTS: Respondents reported
      changes in practice behaviour due to medicolegal concerns, with 43% of doctors
      stating that they referred patients more than usual, 55% stating that they
      ordered tests more than usual, and 11% stating that they prescribed medications
      more than usual. Respondents also reported improved communication of risk (66%),
      increased disclosure of uncertainty (44%), developed better systems for tracking
      results (48%) and better methods for identifying non-attenders (39%) and for
      auditing clinical practice (35%). Concerns about medicolegal issues led to 33%
      considering giving up medicine, 32% considering reducing their working hours and
      40% considering retiring early. These proportions were all significantly greater
      for doctors who had previously experienced a medicolegal matter compared with
      those who had not. CONCLUSIONS: This Australian study, like international
      studies, confirms that doctors' concerns about medicolegal issues impact on their
      practice in a variety of ways. There is a greater perceived impact on those
      doctors who have previously experienced a medicolegal matter.

PMID- 21077814
TI  - Twenty-five years of treatment for childhood acute lymphoblastic leukaemia in
      Western Australia: how do we compare?
AB  - OBJECTIVES: To compare survival among the subgroup of children with acute
      lymphoblastic leukaemia (ALL) who were treated at Princess Margaret Hospital for
      Children (PMH) in Perth, Western Australia, over 25 years under 15 consecutive
      protocols of the Children's Cancer Group (CCG) with survival for the entire
      cohort of children in multiple centres treated under CCG protocols in that
      period; and to highlight the benefits of membership of a large cooperative
      research group conducting multicentre randomised controlled trials. DESIGN,
      PARTICIPANTS AND SETTING: Retrospective review of the outcomes of all 311
      children with newly diagnosed ALL treated at PMH between 1983 and 2008. MAIN
      OUTCOME MEASURES: 4-year event-free survival; and 10-year overall survival.
      RESULTS: Four-year event-free survival for the entire PMH cohort increased from
      66% (SE, 6%) for 1983-1987 to 88% (SE, 6%) for 2002-2005, while overall survival
      over the same period improved from 78% (SE, 5%) to 94% (SE, 4%). Comparisons of
      outcomes of children treated at PMH with those of the entire CCG cohort, protocol
      by protocol, revealed similar outcomes. CONCLUSION: Outcomes of children treated
      at PMH over the 25-year period are equivalent to those of the larger CCG cohort.

PMID- 21077815
TI  - Cancer incidence and mortality in Indigenous Australians in Queensland, 1997
      2006.
AB  - OBJECTIVE: To examine cancer incidence and mortality in Indigenous Queenslanders.
      DESIGN, SETTING AND PATIENTS: Assessment of indirectly standardised incidence and
      mortality ratios for Indigenous Australians in Queensland diagnosed with cancer
      from 1997 to 2006, compared with the total Queensland population. MAIN OUTCOME
      MEASURES: Standardised incidence and mortality ratios. RESULTS: Compared with the
      total Queensland population, Indigenous Queenslanders had a lower overall
      incidence of cancer (standardised incidence ratio, 0.79; 95% CI, 0.75-0.82), but
      a higher incidence of some of the more fatal cancer types. Overall cancer
      mortality was higher (standardised mortality ratio, 1.36; 95% CI, 1.28-1.45) and
      similar to rates for Indigenous people in other Australian states. CONCLUSION:
      Cancer rates for Indigenous Queenslanders, a mostly urbanised population, are
      similar to rates for Indigenous Australians mostly living in remote areas.

PMID- 21077816
TI  - Per capita alcohol consumption in Australia: will the real trend please step
      forward?
AB  - OBJECTIVE: To estimate the national trend in per capita consumption (PCC) of
      alcohol for Australians aged 15 years and older for the financial years 1990-91
      to 2008-09. DESIGN AND SETTING: With the use of data obtained from Australian
      Bureau of Statistics' catalogues and World Advertising Research Centre reports,
      three alternative series of annual totals of PCC of alcohol for the past 20 years
      (1990-91 to 2008-09) were estimated based on different assumptions about the
      alcohol content of wine. For the "old" series, the alcohol content of wine was
      assumed to have been stable over time. For the "new" series, the alcohol content
      of wine was assumed to have increased once in 2004-05 and then to have remained
      stable to 2008-09. For the "adjusted" series, the alcohol content of wine was
      assumed to have gradually increased over time, beginning in 1998-99. Linear trend
      analysis was applied to identify significant trends. MAIN OUTCOMES MEASURE:
      National trend in annual PCC of alcohol 1990-91 to 2008-09. RESULTS: The new and
      adjusted series of annual totals of PCC of alcohol showed increasing trends; the
      old series was stable. CONCLUSIONS: Until recently, official national annual
      totals of PCC of alcohol were underestimated and led to the mistaken impression
      that levels of alcohol consumption had been stable since the early 1990s. In
      fact, Australia's total PCC has been increasing significantly over time because
      of a gradual increase in the alcohol content and market share of wine and is now
      at one of its highest points since 1991-92. This new information is consistent
      with evidence of increasing alcohol-related harm and highlights the need for
      timely and accurate data on alcohol sales and harms across Australia.

PMID- 21077817
TI  - The 500-bed hospital that isn't there: the Victorian Department of Health review
      of the Hospital in the Home program.
AB  - The Victorian Department of Health reviewed its Hospital in the Home (HIH)
      program in 2009, for the first time in a decade. Annual reimbursements to all
      Victorian hospitals for HIH care had reached $110 million. Nearly all Victorian
      hospitals have an HIH program. Collectively, these units recorded 32,462
      inpatient admissions in 2008-09, representing 2.5% of all inpatient admissions,
      5.3% of multiday admissions and 5% of all bed-days in Victoria. If HIH were a
      single entity, it would be a 500-bed hospital. Treatment of many patients with
      acute community- and hospital-acquired infections or venous thromboembolism has
      moved into HIH. There is still capacity for growth in clinical conditions that
      can be appropriately managed at home. The review found evidence of gaming by
      hospitals through deliberate blurring of boundaries between acute HIH care and
      postacute care. The Victorian HIH program is a remarkable success that has
      significantly expanded the overall capacity of the hospital system, with lower
      capital resources. It suggests HIH with access to equivalent hospital
      remuneration is necessary for a successful HIH policy. Hospitals should invest in
      HIH medical leadership and supervision to expand their HIH services, including
      teaching. HIH is a challenge to the traditional vision of a hospital. Greater
      community awareness of HIH could assist in its continued growth.

PMID- 21077818
TI  - Can clinical governance deliver quality improvement in Australian general
      practice and primary care? A systematic review of the evidence.
AB  - OBJECTIVES: To review the literature on different models of clinical governance
      and to explore their relevance to Australian primary health care, and their
      potential contributions on quality and safety. DATA SOURCES: 25 electronic
      databases, scanning reference lists of articles and consultation with experts in
      the field. We searched publications in English after 1999, but a search of the
      German language literature for a specific model type was also undertaken. The
      grey literature was explored through a hand search of the medical trade press and
      websites of relevant national and international clearing houses and professional
      or industry bodies. 11 software packages commonly used in Australian general
      practice were reviewed for any potential contribution to clinical governance.
      STUDY SELECTION: 19 high-quality studies that assessed outcomes were included.
      DATA EXTRACTION: All abstracts were screened by one researcher, and 10% were
      screened by a second researcher to crosscheck screening quality. Studies were
      reviewed and coded by four reviewers, with all studies being rated using standard
      critical appraisal tools such as the Strengthening the Reporting of Observational
      Studies in Epidemiology checklist. Two researchers reviewed the Australian
      general practice software. Interviews were conducted with 16 informants
      representing service, regional primary health care, national and international
      perspectives. DATA SYNTHESIS: Most evidence supports governance models which use
      targeted, peer-led feedback on the clinician's own practice. Strategies most used
      in clinical governance models were audit, performance against indicators, and
      peer-led reflection on evidence or performance. CONCLUSIONS: The evidence base
      for clinical governance is fragmented, and focuses mainly on process rather than
      outcomes. Few publications address models that enhance safety, efficiency,
      sustainability and the economics of primary health care. Locally relevant
      clinical indicators, the use of computerised medical record systems, regional
      primary health care organisations that have the capacity to support the uptake of
      clinical governance at the practice level, and learning from the Aboriginal
      community-controlled sector will help integrate clinical governance into primary
      care.

PMID- 21077819
TI  - To teach or not to teach? A cost-benefit analysis of teaching in private general
      practice.
AB  - OBJECTIVE: To identify the financial costs and benefits associated with teaching
      in private general practice. DESIGN: Cost-benefit analysis of teaching in private
      general practice across three levels of training--undergraduate medical training,
      prevocational training and general practice vocational training--using data from
      a 2007 survey of general practitioners in South Australia. SETTING AND
      PARTICIPANTS: GPs and practices teaching in association with the Adelaide to
      Outback GP Training Program or the Discipline of General Practice at the
      University of Adelaide. MAIN OUTCOME MEASURE: Net financial outcome per week.
      RESULTS: The net financial outcome of teaching varied across the training levels.
      Practices incurred a net financial cost from teaching medical students that was
      statistically significantly different from zero. With respect to vocational
      training and teaching junior doctors, there were small net financial benefits to
      practices, although the mean estimates were not statistically significantly
      different from zero. CONCLUSIONS: This study shows a net financial cost for
      practices teaching medical students, while at the prevocational and vocational
      training levels, adequate levels of subsidies and income generated by the
      trainees help offset the costs of teaching. Our results suggest that a review of
      subsidies for undergraduate teaching is necessary, particularly as the demand for
      teaching practices will increase substantially over the next 5 years.

PMID- 21077820
TI  - Infant botulism in Australia: availability of human botulinum antitoxin for
      treatment.
AB  - We report the first Australian case of treatment of infant botulism with a human
      botulinum antitoxin developed in the United States by the California Department
      of Public Health. Our patient's clinical improvement was rapid, and although the
      product is expensive, cost-analysis supports the economical viability of its use.
      In future cases of suspected infant botulism, we recommend that Australian
      clinicians promptly obtain and administer this antitoxin to their patient.

PMID- 21077821
TI  - Artefactual elevation of creatinine due to creatine water supplements.

PMID- 21077822
TI  - Trends in head injuries and helmet use in cyclists at an inner-city major trauma
      centre, 1991-2010.

PMID- 21077823
TI  - The ABC breast cancer cluster: the bad news about a good outcome. Comment.

PMID- 21077824
TI  - Trends in the incidence of hospitalisation for injuries resulting from non
      traffic crashes in New South Wales, July 1998 to June 2007. Comment.

PMID- 21077825
TI  - Fifteen years of bowel cancer screening policy in Australia: putting evidence
      into practice? Comment.

PMID- 21077826
TI  - Australia needs a national centre for disease control.

PMID- 21077827
TI  - Role of 4-hydroxy-trans-2-nonenal in cell functions.
AB  - The role of lipid peroxidation product 4-hydroxy-trans-2-nonenal (4-HNE) in
      functional activity of cells under normal and different pathological conditions
      is discussed. Different pathways of 4-HNE metabolism in tissues are analyzed,
      with particular focus on the role the glutathione system in this process. 4-HNE
      is implicated in regulation of cell growth, proliferation, differentiation, and
      apoptosis. 4-HNE and metabolic products of other antioxidants (carotenoids)
      resemble each other in chemical nature of the product and influence general
      pathways of signal transduction. Manifestation of 4-HNE toxicity under oxidative
      stress conditions is regarded as a link to many diseases whose pathogenesis is
      connected with modifications of proteins and nucleic acids.

PMID- 21077829
TI  - Toll-like receptors and their adapter molecules.
AB  - Toll-like receptors (TLR) are among key receptors of the innate mammalian immune
      system. Receptors of this family are able to recognize specific highly conserved
      molecular regions (patterns) in pathogen structures, thus initiating reactions of
      both innate and acquired immune response finally resulting in the elimination of
      the pathogen. In this case every individual TLR type is able to bind a broad
      spectrum of molecules of microbial origin characterized by different chemical
      properties and structures. Recent data demonstrate the existence of a multistep
      mechanism of the TLR recognition of the pathogen in which, in addition to
      receptors proper, the involvement of different adapter molecules is necessary.
      However, functions of separate adapter molecules as well as the principles of
      formation of a multicomponent system of ligand-specific recognition are still not
      quite understandable. We describe all identified as well as possible (candidate)
      adapter TLR molecules by giving their brief characteristics, and we also propose
      generalized possible variants of the TLR ligand-specific recognition with
      involvement of adapter molecules.

PMID- 21077828
TI  - Lysophosphatidic acid is a lipid mediator with wide range of biological
      activities. Biosynthetic pathways and mechanism of action.
AB  - Lysophosphatidic acid (LPA) is a lipid mediator required for maintaining
      homeostasis of numerous physiological functions and also involved in development
      of some pathological processes through interactions with G protein-coupled
      receptors. Recently many data have appeared about the role of this phospholipid
      in humans, but pathways of LPA biosynthesis and mechanisms of its action remain
      unclear. This review presents modern concepts about biosynthesis, reception, and
      biological activity of LPA in humans. Natural and synthetic LPA analogs are
      considered in the view of their possible use in pharmacology as agonists and/or
      antagonists of G protein-coupled receptors of LPA.

PMID- 21077830
TI  - Inhibition of murine DNA methyltransferase Dnmt3a by DNA duplexes containing
      pyrimidine-2(1H)-one.
AB  - Here we studied the inhibition of the catalytic domain of Dnmt3a
      methyltransferase (Dnmt3a-CD) by DNA duplexes containing the mechanism-based
      inhibitor pyrimidine-2(1H)-one (P) instead of the target cytosine. It has been
      shown that conjugates of Dnmt3a-CD with P-DNA (DNA containing pyrimidine-2(1H)
      one) are not stable to heating at 65 degrees C in 0.1% SDS. The yield of covalent
      intermediate increases in the presence of the regulatory factor Dnmt3L. The
      importance of the DNA minor groove for covalent intermediate formation during the
      methylation reaction catalyzed by Dnmt3a-CD has been revealed. P-DNA was shown to
      inhibit Dnmt3a-CD; the IC(50) is 830 nM. The competitive mechanism of inhibition
      of Dnmt3a-CD by P-DNA has been elucidated. It is suggested that therapeutic
      effect of zebularine could be achieved by inhibition of not only Dnmt1 but also
      Dnmt3a.

PMID- 21077831
TI  - Ornithine decarboxylase activity in rat organs and tissues under artificial
      hypobiosis.
AB  - The influence of hypothermia-hypoxia-hypercapnia on ornithine decarboxylase (ODC,
      EC 4.1.1.17) activities in rat organs and tissues and also on the thymocyte
      distribution throughout the cell cycle stages was studied. The state of
      artificial hypobiosis in rats on decrease in the body temperature to 14.4-18.0
      degrees C during 3.0-3.5 h was accompanied by drops in the ODC activities in the
      neocortex and liver by 50-60% and in rapidly proliferating tissues (thymus,
      spleen, and small intestine mucosa) by 80% of the control value. In kidneys the
      ODC activity raised to 200% of the control level. Twenty-four hours after
      termination of the cooling and replacing the rats under the standard conditions,
      the ODC activities in the neocortex, liver, kidneys, spleen, and intestinal
      mucosa returned to the control values, but remained decreased in the thymus.
      Forty-eight hours later the ODC activities in the thymus and spleen exceeded the
      normal level. The distribution of thymocytes throughout the cell cycle stages did
      not change in rats in the state of hypothermia (hypobiosis); 24 and 48 h after
      termination of the cooling the fraction of thymocytes in the S stage was
      decreased and the fraction of the cells in the G(0)+G(1) stage was increased. The
      normal distribution of thymocytes throughout the cell cycle stages recovered in
      72 h. Thus, in the thymus the diminution of the ODC activity preceded the
      suppression of the cell proliferation rate. The tissue-specific changes in the
      ODC activity are suggested to reflect adaptive changes in the functional and
      proliferative activities of organs and tissues during the development of
      hypobiosis under conditions of hypothermia-hypoxia-hypercapnia.

PMID- 21077832
TI  - Lipids of nuclear fractions from neurons and glia of rat neocortex under
      conditions of artificial hypobiosis.
AB  - Lipid contents were studied in tissue and nuclei isolated from neurons and glia
      of neocortex of rats under conditions of normothermia and in the state of
      artificial hypobiosis caused by hypothermia-hypoxia-hypercapnia. Compared to the
      neocortex tissue, both nuclear fractions were fivefold impoverished in
      phospholipids and cholesterol and strongly enriched with mono- and diglycerides
      and fatty acids. The nuclear fractions from neurons and glia contained similar
      amounts of phospholipids, and only the cardiolipin content in the neuronal nuclei
      was lower than in the glial nuclei. The state of artificial hypobiosis in rats
      led to an increase in the cholesterol/phospholipids ratio (mol/mol) in the nuclei
      from the neurons and glia; amounts of cholesterol and sphingomyelin in the nuclei
      from the glia were increased. The increases in the cholesterol and sphingomyelin
      contents and in the cholesterol/phospholipids ratio suggest an involvement of
      lipid-dependent signaling systems of the nuclei in the functional response of
      mammalian neocortex cells to artificial hypobiosis.

PMID- 21077833
TI  - Influence of ATP-dependent K(+)-channel opener on K(+)-cycle and oxygen
      consumption in rat liver mitochondria.
AB  - The influence of the K+(ATP)-channel opener diazoxide on the K+ cycle and oxygen
      consumption has been studied in rat liver mitochondria. It was found that
      diazoxide activates the K+(ATP)-channel in the range of nanomolar concentrations
      (50-300 nM, K(1/2) ~ 140 nM), which results in activation of K+/H+ exchange in
      mitochondria. The latter, in turn, accelerates mitochondrial respiration in
      respiratory state 2. The contribution of K+(ATP)-channel to the mitochondrial
      potassium cycle was estimated using the selective K+(ATP)-channel blocker
      glibenclamide. The data show that the relative contribution of K+(ATP)-channel in
      the potassium cycle of mitochondria is variable and increases only with the
      decrease in the ATP-independent component of K+ uptake. Possible mechanisms
      underlying the observed phenomena are discussed. The experimental results more
      fully elucidate the role of K+(ATP)-channel in the regulation of mitochondrial
      functions, especially under pathological conditions accompanied by impairment of
      the mitochondrial energy state.

PMID- 21077834
TI  - Identification of proteins overexpressed in papillary thyroid tumors.
AB  - A modified method of proteome comparative analysis based on preliminary removal
      of cell structural proteins by extraction using salt buffer and subsequent
      separation of extracts by two-dimensional gel electrophoresis was developed.
      Identification of differentially expressed proteins by mass spectrometry has
      revealed three proteins with noticeably increased level of synthesis in most
      samples of papillary thyroid tumors compared to normal tissues. An increase in
      ubiquitin content was found for the first time. Oncomarker search efficiencies by
      two-dimensional gel electrophoresis and bioinformatic search were compared.

PMID- 21077835
TI  - Effect of enteropeptidase on survival of cultured hippocampal neurons under
      conditions of glutamate toxicity.
AB  - The effects of full-size bovine enteropeptidase (BEK) and of human recombinant
      light chain enteropeptidase (L-HEP) on survival of cultured hippocampal neurons
      were studied under conditions of glutamate excitotoxicity. Low concentrations of
      L-HEP or BEK (0.1-1 and 0.1-0.5 nM, respectively) protected hippocampal neurons
      against the death caused by 100 uM glutamate. Using the PAR1 (proteinase
      activated receptor) antagonist SCH 79797, we revealed a PAR1-dependent mechanism
      of neuroprotective action of low concentrations of enteropeptidase. The
      protective effect of full-size enteropeptidase was not observed at the
      concentrations of 1 and 10 nM; moreover, 10 nM of BEK caused death of 88.9% of
      the neurons, which significantly exceeded the cell death caused by glutamate
      (31.9%). Under conditions of glutamate cytotoxicity the survival of neurons was
      26.8% higher even in the presence of 10 nM of L-HEP than in the presence of 10 nM
      BEK. Pretreatment of cells with 10 nM of either form of enteropeptidase abolished
      the protective effect of 10 nM thrombin under glutamate cytotoxicity. High
      concentrations of BEK and L-HEP caused the death of neurons mainly through
      necrosis.

PMID- 21077836
TI  - Enzymes of SPZ7 phage: isolation and properties.
AB  - Bacteriophage enzyme preparations exolysin and endolysin were studied. Exolysin
      (a phage-associated enzyme) was obtained from tail fraction and endolysin from
      phage-free cytoplasmic fraction of disintegrated Salmonella enteritidis cells. A
      new method for purification of these enzymes was developed, and their molecular
      masses were determined. The main catalytic properties of the studied enzymes (pH
      optimum and specificity to bacterial substrates) were found to be similar. Both
      enzymes lyse Escherichia coli cells like chicken egg lysozyme, but more
      efficiently lyse S. enteritidis cells and cannot lyse Micrococcus luteus, a good
      substrate for chicken egg lysozyme. Similar properties of exolysin and endolysin
      suggest that these enzymes are structurally similar or even identical.

PMID- 21077837
TI  - Study of peptide fractions from hemolymph of Galleria mellonella.
AB  - Changes in the peptide composition of hemolymph of Galleria mellonella larvae
      induced by their immunization have been studied, and some new peptides have been
      found. The composition of fractions exhibiting antibacterial activity was
      investigated. Known antibacterial peptides have been found in the hemolymph of
      control larvae and those immunized with bacteria.

PMID- 21077838
TI  - Destabilase-lysozyme of medicinal leech. Multifunctionality of recombinant
      protein.
AB  - Preparation and purification of a recombinant protein are described along with
      characteristics of its specific (for epsilon-(gamma-Glu)-Lys and D-dimer
      substrates) and nonspecific (for L-gamma-Glu-pNA) isopeptidase activities; the
      absence of peptidase function for alpha-(alpha-Glu)-Lys substrate is noted. It is
      shown that the protein exhibits muramidase (cell walls of Micrococcus
      lysodeikticus) and specific glycosidase activities. The latter was determined
      towards the fluorogenic substrate 4-methylumbelliferyl-tetra-N-acetyl-beta
      chitotetraoxide. Antimicrobial activity of recombinant destabilase-lysozyme
      protein (recDest-Lys) and its 11-membered amphipathic peptide was revealed
      towards cells of the strict anaerobic Archaean Methanosarcina barkeri, whose cell
      walls contain no murein. Possible mechanisms of the effect of recDest-Lys on
      these cells are discussed.

PMID- 21077839
TI  - Current strategies in lead discovery.

PMID- 21077840
TI  - Natural products for the healthy heart.

PMID- 21077841
TI  - New approaches to target gram-negative bacteria.

PMID- 21077842
TI  - Recent intellectual property law changes and their impact on drug discovery.

PMID- 21077844
TI  - Non-coding RNAs and their epigenetic regulatory mechanisms.
AB  - It is widely accepted that ncRNAs (non-coding RNAs), as opposed to protein-coding
      RNAs, represent the majority of human transcripts; and the regulatory roles of
      many of these ncRNAs have been elucidated over the past decade. One important
      role so far recognized for ncRNAs is their participation in the epigenetic
      regulation of genes. Indeed, it is becoming increasingly apparent that most
      epigenetic mechanisms of gene expression are controlled by ncRNAs. In this
      review, the different types of ncRNA that are strongly linked to epigenetic
      regulation are characterized and their possible mechanisms discussed.

PMID- 21077845
TI  - Consequences of persistent pain after lung cancer surgery: a nationwide
      questionnaire study.
AB  - BACKGROUND: post-thoracotomy pain syndrome (PTPS) and its social consequences
      have been inconsistently investigated as most studies were either small sized,
      focused on a limited number of risk factors or included heterogeneous surgical
      procedures. The current objectives were to obtain detailed information on the
      consequences of PTPS after thoracotomy and video-assisted thoracic surgery (VATS)
      from homogenous unselected nationwide data, and to suggest mechanisms for the
      development of PTPS. METHODS: data from 1327 patients were collected using a
      prospective national database and combined with a detailed questionnaire.
      RESULTS: the response rate was 81.5%, resulting in 546 patients without prior
      thoracic surgery for the final analysis. Follow-up was 22 months (range 12-36).
      PTPS occurred in 33% thoracotomy patients and 25% VATS patients. Clinically
      relevant pain was present in 11-18% of the patients and severe pain in 4-12%
      depending on the level of physical activity. In PTPS patients, 64% also had pain
      from other locations on the body. Perceived sensory changes in the thoracic area
      were present in 63% of PTPS patients vs. 25% in pain-free patients (P<0.001).
      When comparing VATS with thoracotomy, no consistent differences in the
      prevalence, distribution of pain, sensory changes or effect of pain on daily
      activities were observed although clinically relevant and severe pain was reduced
      after VATS. CONCLUSIONS: this nationwide study corroborates that PTPS is a
      clinically relevant problem influencing daily activities a long time after
      thoracotomy and VATS. Nerve injury and increased pain responsiveness may explain
      the majority of symptoms, the prevalence and distribution of pain including
      perceived sensory sensations.

PMID- 21077843
TI  - How ubiquitination and autophagy participate in the regulation of the cell
      response to bacterial infection.
AB  - Bacterial infection relies on the micro-organism's ability to orchestrate the
      host's cell signalling such that the immune response is not activated.
      Conversely, the host cell has dedicated signalling pathways for coping with
      intrusions by pathogens. The autophagy of foreign micro-organisms (known as
      xenophagy) has emerged as one of the most powerful of these pathways, although
      the triggering mode remains largely unknown. In the present paper, we discuss the
      role that certain post-translational modifications (primarily ubiquitination) may
      play in the activation of xenophagy and how some bacteria have evolved mechanisms
      to subvert or hijack this process. In particular, we address the role played by
      P62/SQSTM1 (sequestosome 1). Finally, we discuss how autophagy can be subverted
      to eliminate bacteria-induced danger signals.

PMID- 21077846
TI  - Noise exposure is increased with neonatal helmet CPAP in comparison with
      conventional nasal CPAP.
AB  - BACKGROUND: in adults, noninvasive ventilation via a helmet is associated with
      significantly greater noise than nasal and facial masks. We hypothesized that
      noise exposure could be increased with neonatal helmet continuous positive airway
      pressure (CPAP) in comparison with conventional nasal CPAP (nCPAP). Our primary
      objective was to compare the noise intensity produced by a neonatal helmet CPAP
      and a conventional nCPAP system. Furthermore, we aimed to evaluate the effect of
      the gas flow rate and the presence of the humidifier and the filter on noise
      levels during neonatal helmet CPAP treatment. METHODS: in this bench study, noise
      intensity was measured in the following settings: helmet CPAP, nCPAP, incubator
      and the neonatal intensive care unit. In helmet CPAP, noise measurements were
      performed at different gas flow rates (8, 10 and 12 l/min), while in nCPAP, the
      flow rate was 8 l/min. For both CPAP systems, the level of pressure was
      maintained constant at 5 cmH(2) O. RESULTS: during neonatal helmet CPAP, the
      median (interquartile range) noise levels were significantly higher than those
      during nCPAP: 70.0 dB (69.9-70.4) vs. 62.7 dB (62.5-63.0); P<0.001. In the helmet
      CPAP, the noise intensities changed with increasing flow rate and with the
      presence of a humidifier or a filter. CONCLUSIONS: noise intensities generated by
      the neonatal helmet CPAP were significantly higher than those registered while
      using a conventional nCPAP system. In the helmet, the noise intensity depends on
      the gas flow rate, and the presence of a humidifier and a filter in the system.

PMID- 21077848
TI  - Tetramethylphenylenediamine protects the isolated heart against ischaemia-induced
      apoptosis and reperfusion-induced necrosis.
AB  - BACKGROUND AND PURPOSE: Cytochrome c when released from mitochondria into cytosol
      triggers assembly of the apoptosome resulting in caspase activation. Recent
      evidence suggests that reduced cytochrome c is unable to activate the caspase
      cascade. In this study, we investigated whether a chemical reductant of
      cytochrome c, N,N,N',N'-tetramethylphenylene-1,4-diamine (TMPD), which we have
      previously shown to block cytochrome c-induced caspase activation, could prevent
      ischaemia-induced apoptosis in the rat perfused heart. EXPERIMENTAL APPROACH: The
      Langendorff-perfused rat hearts were pretreated with TMPD and subjected to stop
      flow ischaemia or ischaemia/reperfusion. The activation of caspases (measured as
      DEVD-p-nitroanilide-cleaving activity), nuclear apoptosis of cardiomyocytes
      (measured by dUTP nick end labelling assay), mitochondrial and cytosolic levels
      of cytochrome c (measured spectrophotometrically and by elisa), and reperfusion
      induced necrosis (measured as the activity of creatine kinase released into
      perfusate) were assessed. KEY RESULTS: We found that perfusion of the hearts with
      TMPD strongly inhibited ischaemia- or ischaemia/reperfusion-induced activation of
      caspases and partially prevented nuclear apoptosis in cardiomyocytes. TMPD did
      not prevent ischaemia- or ischaemia/reperfusion-induced release of cytochrome c
      from mitochondria into cytosol. TMPD also inhibited ischaemia/reperfusion-induced
      necrosis. CONCLUSIONS AND IMPLICATIONS: These results suggest that TMPD or
      related molecules might be used to protect the heart against damage induced by
      ischaemia/reperfusion. The mechanism of this protective effect of TMPD probably
      involves electron reduction of cytochrome c (without decreasing its release)
      which then inhibits the activation of caspases.

PMID- 21077847
TI  - Valproic acid and phenobarbital blood levels during the first month of treatment
      with the ketogenic diet.
AB  - OBJECTIVE: The aim of this study was to assess how the ketogenic diet influences
      the blood levels of antiepileptic drugs in the first month of treatment in a
      pediatric population with drug-resistant epilepsy. METHODS: The plasma
      concentrations of antiepileptic drugs were investigated in an open study on 36
      consecutive children and adolescents (20 males), aged between 6 months and 16
      years (mean age 4.7 years), who were put on the ketogenic diet because of
      medically refractory epilepsy. The plasma levels of antiepileptic drugs were
      determined 30 days and immediately before the diet and on days 8, 15, 22 and 29
      after the start of the diet. The daily dose of each drug was not changed during
      the first month of treatment, while the daily dose of benzodiazepines was reduced
      by up to 30% if excessive sedation or drowsiness occurred. RESULTS: While plasma
      concentrations of phenobarbital did not change in the first month on the
      ketogenic diet (mean increase of 2.3 mg/l +/- 1.0), valproic acid showed a slight
      but not significant decrease (mean decrease of 6.7 mg/l +/- 3.2), 2 weeks after
      the start of the diet. CONCLUSIONS: Adjustments in the daily dose of either drug
      before the start of the diet do not however appear to be justified.

PMID- 21077849
TI  - Protein isoprenylation regulates osteogenic differentiation of mesenchymal stem
      cells: effect of alendronate, and farnesyl and geranylgeranyl transferase
      inhibitors.
AB  - BACKGROUND AND PURPOSE: Protein isoprenylation is an important step in the
      intracellular signalling pathway conducting cell growth and differentiation. In
      bone, protein isoprenylation is required for osteoclast differentiation and
      activation. However, its role in osteoblast differentiation and function remains
      unknown. In this study, we assessed the role of protein isoprenylation in
      osteoblastogenesis in a model of mesenchymal stem cells (MSC) differentiation.
      EXPERIMENTAL APPROACH: We tested the effect of an inhibitor of farnesylation
      [farnesyl transferase inhibitor-277 (FTI-277)] and one of geranylgeranylation
      [geranylgeranyltransferase inhibitor-298 (GGTI-298)] on osteoblast
      differentiating MSC. In addition, we tested the effect of alendronate on protein
      isoprenylation in this model either alone or in combination with other inhibitors
      of isoprenylation. KEY RESULTS: Initially, we found that levels of unfarnesylated
      proteins (prelamin A and HDJ-2) increased after treatment with FTI-277
      concomitantly affecting osteoblastogenesis and increasing nuclear morphological
      changes without affecting cell survival. Furthermore, inhibition of
      geranylgeranylation by GGTI-298 alone increased osteoblastogenesis. This effect
      was enhanced by the combination of GGTI-298 and alendronate in the osteogenic
      media. CONCLUSIONS AND IMPLICATIONS: Our data indicate that both farnesylation
      and geranylgeranylation play a role in osteoblastogenesis. In addition, a new
      mechanism of action for alendronate on protein isoprenylation in osteogenic
      differentiating MSC in vitro was found. In conclusion, protein isoprenylation is
      an important component of the osteoblast differentiation process that could
      constitute a new therapeutic target for osteoporosis in the future.

PMID- 21077850
TI  - Betulinic acid inhibits endotoxin-stimulated phosphorylation cascade and pro
      inflammatory prostaglandin E(2) production in human peripheral blood mononuclear
      cells.
AB  - BACKGROUND AND PURPOSE: Betulinic acid (BA) is a naturally occurring triterpenoid
      widely distributed throughout the plant kingdom. We previously reported that BA
      inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through
      modulation of nuclear factor kappaB (NF-kappaB) in human peripheral blood
      mononuclear cells (hPBMCs). This study attempted to identify other mechanisms
      through which BA modulates LPS signalling in mononuclear cells. The effects of BA
      on signalling pathways downstream were focused on in this study. EXPERIMENTAL
      APPROACH: We determined the ability of BA to interfere with p38 and extracellular
      regulated kinase (ERK) phosphorylation as well as Akt phosphorylation and nuclear
      factor-kappaB activation using LPS-activated hPBMCs as an in vitro model. LPS
      induced endotoxin shock in mice was the in vivo model employed. KEY RESULTS: BA
      inhibited LPS-induced COX-2 protein expression and prostaglandin E(2) production
      and also attenuated LPS-induced ERK and Akt phosphorylation, but not p38 in
      hPBMCs. BA abolished LPS-induced IkappaBalpha phosphorylation and thus normalized
      the levels of IkappaBalpha in cytosol. BA also inhibited LPS-induced reactive
      oxygen species formation and lactate dehydrogenase release. Interestingly, BA
      improved the life span of mice in endotoxin shock and also inhibited PGE(2)
      production and myeloperoxidase activity in vivo. CONCLUSIONS AND IMPLICATIONS: BA
      modulates LPS-induced COX-2 expression in hPBMCs by inhibiting ERK and Akt
      pathways as well as by modulating IkappaBalpha phosphorylation. At the same time,
      no cell toxicity was observed. The effect of the drug was confirmed through in
      vivo experiments. The study gives an insight into the molecular mechanisms of BA.

PMID- 21077851
TI  - The omega-3 epoxide of eicosapentaenoic acid inhibits endothelial cell
      proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation.
AB  - BACKGROUND AND PURPOSE: Dietary intake of omega-3 polyunsaturated fatty acids
      (omega-3 PUFAs) like eicosapentaenoic acid (EPA) decreases cancer risk, while
      arachidonic acid and other omega-6 PUFAs increase risk, but the underlying
      mechanisms are unclear. Cytochrome P450 (CYP)-derived epoxides contribute to
      enhanced tumourigenesis due to omega-6 PUFA intake. Thus, omega-6 arachidonic
      acid epoxides (EETs) inhibit apoptosis and stimulate proliferation by up
      regulating cyclin D1 expression in cells. The present study evaluated the
      corresponding omega-3 PUFA epoxides and assessed their role in the regulation of
      cell proliferation. EXPERIMENTAL APPROACH: Four chemically stable EPA epoxides
      (formed at the 8,9-, 11,12-, 14,15- and 17,18-olefinic bonds) were synthesized
      and tested against growth-related signalling pathways in brain microvascular
      endothelial bEND.3 cells. Cell cycle distribution was determined by flow
      cytometry and cyclin gene expression by immunoblotting and real-time PCR. The
      role of the p38 mitogen-activated protein (MAP) kinase in cyclin D1 dysregulation
      was assessed using specific inhibitors and dominant-negative expression plasmids.
      KEY RESULTS: The omega-3 17,18-epoxide of EPA decreased cell proliferation,
      interrupted the cell cycle in S-phase and down-regulated the cyclin D1/cyclin
      dependent kinase (CDK)-4 complex, whereas the 8,9-, 11,12- and 14,15-epoxides
      were either inactive or enhanced proliferation. Cyclin D1 down-regulation by
      17,18-epoxy-EPA was mediated by activation of the growth-suppressing p38 MAP
      kinase, but the alternate EPA-epoxides were inactive. CONCLUSIONS AND
      IMPLICATIONS: The present findings suggest that the epoxide formed by CYP enzymes
      at the omega-3 olefinic bond may contribute to the beneficial effects of omega-3
      PUFA by down-regulating cyclin D1 and suppressing cell proliferation.

PMID- 21077854
TI  - Young children selectively avoid helping people with harmful intentions.
AB  - Two studies investigated whether young children are selectively prosocial toward
      others, based on the others' moral behaviors. In Study 1 (N = 54), 3-year-olds
      watched 1 adult (the actor) harming or helping another adult. Children
      subsequently helped the harmful actor less often than a third (previously
      neutral) adult, but helped the helpful and neutral adults equally often. In Study
      2 (N = 36), 3-year-olds helped an actor who intended but failed to harm another
      adult less often than a neutral adult, but helped an accidentally harmful and a
      neutral adult equally often. Children's prosocial behavior was thus mediated by
      the intentions behind the actor's moral behavior, irrespective of outcome.
      Children thus selectively avoid helping those who cause--or even intend to cause-
      others harm.

PMID- 21077853
TI  - A developmental perspective on executive function.
AB  - This review article examines theoretical and methodological issues in the
      construction of a developmental perspective on executive function (EF) in
      childhood and adolescence. Unlike most reviews of EF, which focus on
      preschoolers, this review focuses on studies that include large age ranges. It
      outlines the development of the foundational components of EF-inhibition, working
      memory, and shifting. Cognitive and neurophysiological assessments show that
      although EF emerges during the first few years of life, it continues to
      strengthen significantly throughout childhood and adolescence. The components
      vary somewhat in their developmental trajectories. The article relates the
      findings to long-standing issues of development (e.g., developmental sequences,
      trajectories, and processes) and suggests research needed for constructing a
      developmental framework encompassing early childhood through adolescence.

PMID- 21077855
TI  - Prospective associations between peer victimization and aggression.
AB  - The current study involved a short-term longitudinal study of young children (M =
      44.56 months, SD = 11.88, N = 103) to test the prospective associations between
      peer victimization and aggression subtypes. Path analyses documented that teacher
      reported physical victimization was uniquely associated with increases in
      observed physical aggression over time. The path model also revealed that teacher
      reported relational victimization was uniquely associated with statistically
      significant increases in observed relational aggression over time. Ways in which
      these findings extend the extant developmental literature are discussed.

PMID- 21077856
TI  - Development in children's comprehension of linguistic register.
AB  - For socially appropriate communication, speakers must command a variety of
      linguistic styles, or registers, that vary according to social context and social
      relationships. This study examined preschool children's ability to use a
      speaker's register choice to infer the identity of their addressee. Four-year
      olds could draw correct inferences based on Spanish and formal speech, and had
      limited success with infant-directed and casual styles. Five-year-olds drew
      appropriate inferences with all 4 styles; moreover, these children demonstrated
      strong explicit understanding of register, as measured through response
      justifications. These results demonstrate that children can use language for
      social judgments that extend beyond evaluating the speaker, and can interpret
      social implications of language even when not directly engaged in the particular
      social interaction.

PMID- 21077857
TI  - Goal neglect and working memory capacity in 4- to 6-year-old children.
AB  - Goal neglect is the phenomenon of failing to execute the momentary demands of a
      task despite understanding and being able to recall the task instructions.
      Successful goal maintenance is more likely to occur in adults with high working
      memory capacity (WMC) who can keep rules mentally accessible while performing the
      task. The current study predicted that goal neglect would also be related to WMC
      in children. It assessed thirty-seven 4-year-old and twenty-eight 6-year-old
      children on the goal neglect version of the Dimensional Change Card Sort, and 3
      tasks that measure WMC. As predicted, children with higher WMC scores were more
      likely to maintain goals adequately for task performance. The findings are
      consistent with a 2-factor model of working memory and its development.

PMID- 21077858
TI  - The social costs of academic success across ethnic groups.
AB  - This study explores the longitudinal association between academic achievement and
      social acceptance across ethnic groups in a nationally representative sample of
      adolescents (N = 13,570; M(age) = 15.5 years). The effects of school context are
      also considered. Results show that African American and Native American
      adolescents experience greater social costs with academic success than Whites.
      Pertaining to school context, findings suggest that the differential social
      consequences of achievement experienced by African Americans are greatest in more
      highly achieving schools, but only when these schools have a smaller percentage
      of Black students. Students from Mexican descent also showed differential social
      costs with achievement in particular contexts. The implications of these findings
      to theory, policy, and future research are discussed.

PMID- 21077860
TI  - Preverbal infants anticipate that food will be brought to the mouth: an eye
      tracking study of manual feeding and flying spoons.
AB  - This study relies on eye tracking technology to investigate how humans perceive
      others' feeding actions. Results demonstrate that 6-month-olds (n = 54)
      anticipate that food is brought to the mouth when observing an adult feeding
      herself with a spoon. Still, they fail to anticipate self-propelled (SP) spoons
      that move toward the mouth and manual combing actions directed toward the head.
      Ten-month-olds (n = 54) and adults (n = 32) anticipate SP spoons; however, only
      adults anticipate combing actions. These results suggest that goal anticipation
      during observation of feeding actions develops earlier and is less dependent on
      directly perceived actions than goal anticipation during observation of other
      manual actions. These results are discussed in relation to experience and a
      possible phylogenetic influence on perception and understanding of feeding.

PMID- 21077859
TI  - Children's reasoning about disclosing adult transgressions: effects of
      maltreatment, child age, and adult identity.
AB  - A total of two hundred ninety-nine 4- to 9-year-old maltreated and nonmaltreated
      children of comparable socioeconomic status and ethnicity judged whether children
      should or would disclose unspecified transgressions of adults (instigators) to
      other adults (recipients) in scenarios varying the identity of the instigator
      (stranger or parent), the identity of the recipient (parent, police, or teacher),
      and the severity of the transgression ("something really bad" or "something just
      a little bad"). Children endorsed more disclosure against stranger than parent
      instigators and less disclosure to teacher than parent and police recipients. The
      youngest maltreated children endorsed less disclosure than nonmaltreated
      children, but the opposite was true among the oldest children. Older maltreated
      children distinguished less than nonmaltreated children between parents and other
      types of instigators and recipients.

PMID- 21077861
TI  - Relations between physiological and cognitive regulatory systems: infant sleep
      regulation and subsequent executive functioning.
AB  - The aim of this report was to investigate the prospective links between infant
      sleep regulation and subsequent executive functioning (EF). The authors assessed
      sleep regulation through a parent sleep diary when children were 12 and 18 months
      old (N = 60). Child EF was assessed at 18 and 26 months of age. Higher
      proportions of total sleep occurring at night time, at both 12 and 18 months,
      were related to better performance on executive tasks, especially those involving
      a strong impulse control component. Most relations held above family
      socioeconomic status, prior mental development and concurrent verbal ability.
      These findings add to previous results with school-age children in suggesting
      that sleep favors the development of higher order cognitive functions requiring
      prefrontal cortex involvement.

PMID- 21077862
TI  - Pathways to mathematics: longitudinal predictors of performance.
AB  - A model of the relations among cognitive precursors, early numeracy skill, and
      mathematical outcomes was tested for 182 children from 4.5 to 7.5 years of age.
      The model integrates research from neuroimaging, clinical populations, and normal
      development in children and adults. It includes 3 precursor pathways:
      quantitative, linguistic, and spatial attention. These pathways (a) contributed
      independently to early numeracy skills during preschool and kindergarten and (b)
      related differentially to performance on a variety of mathematical outcomes 2
      years later. The success of the model in accounting for performance highlights
      the need to understand the fundamental underlying skills that contribute to
      diverse forms of mathematical competence.

PMID- 21077863
TI  - How 15 hundred is like 15 cherries: effect of progressive alignment on
      representational changes in numerical cognition.
AB  - How does understanding the decimal system change with age and experience? Second,
      third, sixth graders, and adults (Experiment 1: N = 96, mean ages = 7.9, 9.23,
      12.06, and 19.96 years, respectively) made number line estimates across 3 scales
      (0-1,000, 0-10,000, and 0-100,000). Generation of linear estimates increased with
      age but decreased with numerical scale. Therefore, the authors hypothesized
      highlighting commonalities between small and large scales (15:100::1500:10000)
      might prompt children to generalize their linear representations to ever-larger
      scales. Experiment 2 assigned second graders (N = 46, mean age = 7.78 years) to
      experimental groups differing in how commonalities of small and large numerical
      scales were highlighted. Only children experiencing progressive alignment of
      small and large scales successfully produced linear estimates on increasingly
      larger scales, suggesting analogies between numeric scales elicit broad
      generalization of linear representations.

PMID- 21077864
TI  - Differing levels of gender salience in preschool classrooms: effects on
      children's gender attitudes and intergroup bias.
AB  - Developmental intergroup theory posits that when environments make social-group
      membership salient, children will be particularly likely to apply categorization
      processes to social groups, thereby increasing stereotypes and prejudices. To
      test the predicted impact of environmental gender salience, 3- to 5-year-old
      children (N = 57) completed gender attitude, intergroup bias, and personal
      preference measures at the beginning and end of a 2-week period during which
      teachers either did or did not make gender salient. Observations of peer play
      were also made at both times. After 2 weeks, children in the high- (but not low-)
      salience condition showed significantly increased gender stereotypes, less
      positive ratings of other-sex peers, and decreased play with other-sex peers.
      Children's own activity and occupational preferences, however, remained
      unaffected.

PMID- 21077865
TI  - Race salience and essentialist thinking in racial stereotype development.
AB  - The authors explored the emergence and antecedents of racial stereotyping in 89
      children ages 3-10 years. Children completed a number of matching and sorting
      tasks, including a measure designed to assess their knowledge and application of
      both positive and negative in-group and out-group stereotypes. Results indicate
      that children start to apply stereotypes to the out-group starting around 6 years
      of age. Controlling for a number of factors, 2 predictors contributed
      significantly toward uniquely explaining the use of these stereotypes: race
      salience (i.e., seeing and organizing by race) and essentialist thinking (i.e.,
      believing that race cannot change). These results provide insight into how and
      when real-world interventions aimed at altering the acquisition of racial
      stereotypes may be implemented.

PMID- 21077866
TI  - Toddlers' prosocial behavior: from instrumental to empathic to altruistic
      helping.
AB  - The study explored how the meaning of prosocial behavior changes over
      toddlerhood. Sixty-five 18- and 30-month-olds could help an adult in 3 contexts:
      instrumental (action based), empathic (emotion based), and altruistic (costly).
      Children at both ages helped readily in instrumental tasks. For 18-month-olds,
      empathic helping was significantly more difficult than instrumental helping and
      required greater communication from the adult about her needs. Altruistic
      helping, which involved giving up an object of the child's own, was the most
      difficult for children at both ages. Findings suggest that over the 2nd year of
      life, prosocial behavior develops from relying on action understanding and
      explicit communications to understanding others' emotions from subtle cues.
      Developmental trajectories of social-cognitive and motivational components of
      early helping are discussed.

PMID- 21077867
TI  - Do Black and Hispanic children benefit more from preschool? Understanding
      differences in preschool effects across racial groups.
AB  - Recent studies suggest that the effects of attending preschool vary by race.
      These findings are difficult to interpret because the likelihood of enrolling a
      child in preschool also differs across groups. This study used newly released,
      nationally representative data to examine whether the impact of preschool
      participation at age 4 varies across racial groups after accounting for selection
      differences (N = 7,400). Among a subsample of children living below a poverty
      threshold, no racial differences in preschool impact are detected. However,
      findings suggest that nonpoor Black children benefit substantially more from
      preschool than their nonpoor White or Hispanic peers. Implications of these
      findings are discussed toward understanding the potential of large-scale
      preschool interventions for narrowing racial achievement gaps.

PMID- 21077868
TI  - Movement planning reflects skill level and age changes in toddlers.
AB  - Kinematic measures of children's reaching were found to reflect stable
      differences in skill level for planning for future actions. Thirty-five toddlers
      (18-21 months) were engaged in building block towers (precise task) and in
      placing blocks into an open container (imprecise task). Sixteen children were
      retested on the same tasks a year later. Longer deceleration as the hand
      approached the block for pickup was found in the tower task compared with the
      imprecise task, indicating planning for the second movement. More skillful
      toddlers who could build high towers had a longer deceleration phase when placing
      blocks on the tower than toddlers who built low towers. Kinematic differences
      between the groups remained a year later when all children could build high
      towers.

PMID- 21077869
TI  - Comprehension of infrequent subject-verb agreement forms: evidence from French
      learning children.
AB  - Two comprehension experiments were conducted to investigate whether young French
      learning children (N = 76) are able to use a single number cue in subject-verb
      agreement contexts and match a visually dynamic scene with a corresponding verbal
      stimulus. Results from both preferential looking and pointing demonstrated
      significant comprehension in 30-month-olds with no preference for either singular
      or plural. These results challenge previous claims made on the basis of English
      and Spanish that comprehension of subject-verb agreement expressed as a bound
      morpheme is late, around 5 years of age (V. A. Johnson, J. G. de Villiers, & H.
      N. Seymour, 2005; A.-T. Perez-Leroux, 2005). Properties of the adult input were
      also analyzed. Possible implications for theories of syntactic acquisition are
      discussed.

PMID- 21077870
TI  - Reading minds: the relation between children's mental state knowledge and their
      metaknowledge about reading.
AB  - The relation between children's mental state knowledge and metaknowledge about
      reading was examined in 2 studies. In Study 1, 196 children (mean age = 9 years)
      were tested for verbal ability (VA), metaknowledge about reading, and mental
      state words in a story task. In Study 2, the results of Study 1 were extended by
      using a cross-lagged design and by investigating older children (N = 71, mean
      ages = 10 years at Time 1 and 11 years at Time 2) for mental state knowledge,
      metaknowledge about reading, and VA. Results showed a significant relation
      between early cognitive (but not emotion) mental state knowledge and later
      metaknowledge about reading, controlling for VA. Results suggest close links
      between different aspects of children's knowledge about the mind.

PMID- 21077871
TI  - Holistic face processing in newborns, 3-month-old infants, and adults: evidence
      from the composite face effect.
AB  - Holistic face processing was investigated in newborns, 3-month-old infants, and
      adults through a modified version of the composite face paradigm and the
      recording of eye movements. After familiarization to the top portion of a face,
      participants (N = 70) were shown 2 aligned or misaligned faces, 1 of which
      comprised the familiar top part. In the aligned condition, no visual preference
      was found at any group age. In the misaligned condition, 3-month-olds preferred
      the face stimulus with the familiar top part, adults preferred the face stimulus
      with the novel one, and newborns did not manifest any visual preference. Results
      revealed that both infants' and adults' eye movements may be affected by holistic
      face information and demonstrated holistic face processing in 3-month-olds.

PMID- 21077872
TI  - Aquifer system response time and groundwater supply management.

PMID- 21077873
TI  - Mitochondrial DNA sequencing of cat hair: an informative forensic tool.
AB  - Approximately 81.7 million cats are in 37.5 million U.S. households. Shed fur can
      be criminal evidence because of transfer to victims, suspects, and/or their
      belongings. To improve cat hairs as forensic evidence, the mtDNA control region
      from single hairs, with and without root tags, was sequenced. A dataset of a 402
      bp control region segment from 174 random-bred cats representing four U.S.
      geographic areas was generated to determine the informativeness of the mtDNA
      region. Thirty-two mtDNA mitotypes were observed ranging in frequencies from 0.6
      27%. Four common types occurred in all populations. Low heteroplasmy, 1.7%, was
      determined. Unique mitotypes were found in 18 individuals, 10.3% of the
      population studied. The calculated discrimination power implied that 8.3 of 10
      randomly selected individuals can be excluded by this region. The genetic
      characteristics of the region and the generated dataset support the use of this
      cat mtDNA region in forensic applications.

PMID- 21077875
TI  - Intravascular bullet embolism to the right atrium.
AB  - Bullet embolism is a relatively unusual complication of gunshot wounds. Embolism
      to the right atrium comprises <5% of all reported intravascular bullet emboli. We
      report an additional case of bullet embolus to the right atrium of a 0.38-caliber
      bullet following a gunshot wound to the chest. The intracardiac bullet was
      recognized radiologically on presentation, but the patient was hemodynamically
      stable and managed conservatively, with the bullet left in place. The missile
      remained within the heart without clinical significance for several years and was
      recovered from the right atrium only at the time of autopsy. To the best of our
      knowledge, this is the first documented case of a 0.38-caliber bullet which
      embolized to the right atrium and remained inconsequential for an extended period
      of time.

PMID- 21077874
TI  - DNAc: A clustering method for identifying kinship relations between DNA profiles
      using a novel similarity measure.
AB  - After decades of refinement, DNA testing methods have become essential tools in
      forensic sciences. They are essentially based on likelihood ratio test principle,
      which is utilized specifically, by using as prior knowledge the allele
      frequencies in the population, to confirm or refute a given kinship hypothesis
      made on two genotypes. This makes these methods ill suited when allele
      frequencies or kinship hypotheses are unavailable. In this paper, we introduce
      DNAc, a new clustering methodology for DNA testing based on a new similarity
      measure that allows an accurate retrieval of the degree of relatedness among two
      or more genotypes, without relying on kinship hypotheses or allele frequencies in
      the population. We used DNAc in analyzing microsatellite DNA sequences
      distributed among 12 genotypes from normal individuals from two distinct
      families. The results show that DNAc accurately determines kinship among
      genotypes and further gathers them in the appropriate kinship groups.

PMID- 21077876
TI  - A comparative research of two lifting methods: electrostatic lifter and gelatin
      lifter.
AB  - Two-dimensional dust shoeprints are often of very high resolution and contain
      unique features. Lifting these prints in the most effective method may contribute
      much to preserving these fine details. A research was conducted by experts from
      Israel and Switzerland to compare gelatin lifters and electrostatic lifters for
      lifting shoeprints. Several substrates were chosen, and on each material a set of
      dry dust shoeprints was made. A set of wet prints was made on paper as well. The
      shoeprints were approximately of the same quality, and the only variable was the
      nature of the material. On substrates indifferent to the method used, the
      preferable sequence was tested. Gelatin lifter was superior on most substrates
      and for wet prints. The superior sequence for using both methods is electrostatic
      lifting followed by gelatin lifter.

PMID- 21077878
TI  - The use of laser scanning confocal microscopy (LSCM) in materials science.
AB  - Laser scanning confocal microscopes are essential and ubiquitous tools in the
      biological, biochemical and biomedical sciences, and play a similar role to
      scanning electron microscopes in materials science. However, modern laser
      scanning confocal microscopes have a number of advantages for the study of
      materials, in addition to their obvious uses for high resolution reflected and
      transmitted light optical microscopy. In this paper, we provide several examples
      that exploit the laser scanning confocal microscope's capabilities of pseudo
      infinite depth of field imaging, topographic imaging, photo-stimulated
      luminescence imaging and Raman spectroscopic imaging.

PMID- 21077877
TI  - Accidental death from hydromorphone ingestion.
AB  - A 15-year-old male orally consumed an unknown but fatal amount of sustained
      release hydromorphone. He was naive to opioid use. No other drugs or alcohol were
      involved. The cause of death was acute aspiration-related bronchopneumonia,
      secondary to hydromorphone ingestion; the manner of death was accidental.
      Hydromorphone and hydromorphone-3-glucuronide were quantified in postmortem
      fluids by tandem liquid chromatography-mass spectrometry. The hydromorphone
      concentrations in the peripheral blood, urine, and vitreous humor were 57, 4460,
      and 31 ng/mL, respectively. The hydromorphone-3-glucuronide concentrations in the
      corresponding three fluids were 459, 36,400, and 40 ng/mL. Hydromorphone-3
      glucuronide accumulation probably did not contribute significantly to the opiate
      toxicity. The proposed minimum lethal hydromorphone blood concentration in the
      nontolerant user is in the vicinity of 60 ng/mL.

PMID- 21077879
TI  - 3D structural analysis: sensitivity of Minkowski functionals.
AB  - The Minkowski functionals, a family of statistical measures based on the Euler
      Poincare characteristic of n-dimensional space, are the complete set of additive
      morphological measures and can be simply calculated from local contributions. As
      such, they have found a wide range of applications. We consider the effects of
      distortions (drift, noise and blurring) on the morphological properties of
      complex random models, representative of a wide range of structure. Such
      distortions arise experimentally in imaging techniques due to diffraction,
      absorption and sample drift. The question is asked, how critically these
      distortions effect image quality as measured by the Minkowski functionals.
      Defining a length scale based on the two-point correlation function, we consider
      how distortion at different scales can lead to quantitative errors in
      morphological measures.

PMID- 21077880
TI  - Noise effects and filtering in controlled light exposure microscopy.
AB  - Phototoxicity and photobleaching are major limitations of fluorescence live-cell
      microscopy. A straightforward way to limit phototoxicity and photobleaching is
      reduction of the excitation light dose, but this causes loss of image quality. In
      confocal fluorescence microscopy, the field of view is illuminated uniformly
      whereas in controlled light exposure microscopy, illumination is controlled per
      pixel on the basis of two illumination strategies. The controlled light exposure
      microscopy foreground strategy discriminates between bright and weak foreground.
      Bright foreground pixels are illuminated with a reduced light dose resulting in
      limited excitation of fluorophores and consequently limited phototoxicity and
      photobleaching. The controlled light exposure microscopy background strategy
      discriminates between foreground and background. Pixels that are judged to be
      background are also illuminated with a reduced light dose. The latter
      illumination strategy may introduce artefacts due to the stochastic character of
      photon flow. These artefacts are visible as erratic 'darker pixels' in the
      foreground with a lower pixel value than the neighbouring pixels. This paper
      describes a special adaptive image processing filter that detects and corrects
      most of the 'darker pixels'. It opens the possibility to use controlled light
      exposure microscopy even in high noise (low signal to noise ratio) imaging to
      further reduce phototoxicity and photobleaching.

PMID- 21077881
TI  - A brain slice bath for physiology and compound microscopy, with dual-sided
      perifusion.
AB  - Contemporary in vitro brain slice studies can employ compound microscopes to
      identify individual neurons or their processes for physiological recording or
      imaging. This requires that the bath used to maintain the tissue fits within the
      working distances of a water-dipping objective and microscope condenser. A common
      means of achieving this is to maintain thin tissue slices on the glass floor of a
      recording bath, exposing only one surface of the tissue to oxygenated bathing
      medium. Emerging evidence suggests that physiology can be compromised by this
      approach. Flowing medium past both sides of submerged brain slices is optimal,
      but recording baths utilizing this principle are not readily available for use on
      compound microscopes. This paper describes a tissue bath designed specifically
      for microscopy and physiological recording, in which temperature-controlled
      medium flows past both sides of the slices. A particular feature of this design
      is the use of concentric mesh rings to support and transport the live tissue
      without mechanical disturbance. The design is also easily adapted for use with
      thin acute slices, cultured slices, and acutely dispersed or cultured cells
      maintained either on cover slips or placed directly on the floor of the bath. The
      low profile of the bath provides a low angle of approach for electrodes, and
      allows use of standard condensers, nosepieces and water-dipping objective lenses.
      If visualization of individual neurons is not required, the bath can be mounted
      on a simple stand and used with a dissecting microscope. Heating is integral to
      the bath, and any temperature controller capable of driving a resistive load can
      be used. The bath is robust, readily constructed and requires minimal
      maintenance. Full construction and operation details are given.

PMID- 21077882
TI  - Contactless determination of nuclear compressibility using 3D image- and model
      based analysis of drug-induced cellular deformation.
AB  - Mechanical properties of the chromatin-bearing nucleus in normal and pathological
      cells are of general interest for epigenetics and medicine. Conventional
      techniques for quantitative measurements of material properties of cellular
      matter are based on application of controlled forces onto the cellular or nuclear
      boundary and do not allow probing intracellular structures that are not directly
      accessible for physical contact inside the living cell. In this work, we present
      a novel approach for contactless determination of the nuclear compressibility
      (i.e. the Poisson's ratio nu) in living cells by means of image- and model-based
      analysis of drug-induced cell deformation. The Poisson's ratio of the HeLa cell
      nucleus is determined from time-series of 3D images as a parameter of
      constitutive model that minimizes the dissimilarity between the numerically
      predicted and experimentally observed images.

PMID- 21077883
TI  - Effect of gallium focused ion beam milling on preparation of aluminium thin
      foils.
AB  - Focussed ion beam milling has greatly extended the utility of the atom probe and
      transmission electron microscope because it enables sample preparation with a
      level of dimensional control never before possible. Using focussed ion beam it is
      possible to extract the samples from desired and very specific locations. The
      artefacts associated with this sample preparation method must also be fully
      understood. In this work, issues specifically relevant to the focussed ion beam
      milling of aluminium alloys are presented. After using the focussed ion beam as a
      sample preparation technique it is evident that gallium will concentrate in three
      areas of the sample: on the surface, on grain boundaries and at interphase
      boundaries. This work also shows that low-energy Ar ion nanomilling is
      potentially quite effective for removing gallium implantation layers and gallium
      from the internal surfaces of aluminium thin foils.

PMID- 21077884
TI  - Morphology and protein adsorption characteristics of block copolymer surfaces.
AB  - Biocompatible polymers are known to act as scaffolds for the regeneration and
      growth of bone. Block copolymers are of interest as scaffold materials because
      novel, structurally diverse polymers can be synthesized from biocompatible
      blocks. Block copolymer nanostructure and surface morphology is easily tunable
      with synthetic techniques and the diverse nanostructures can be used to affect
      cell and tissue behaviour. In this paper, we present atomic force microscopy
      studies on the morphology and corresponding protein adsorption behaviour of a
      novel class of methyl methacrylate and acrylic acid diblock and triblock
      copolymers. The topography, phase angle and adhesion maps were obtained to study
      the morphology. Atomic force microscopy imaging reveals that the diblock and
      triblock copolymers present distinct nanomorphologies, although their chemical
      composition is the same. This has implications on the role of nanomorphology in
      cell-polymer interactions independent of chemical composition. Protein adsorption
      on a biomaterial surface is critical to understanding its biocompatibility and
      bovine serum albumin was used to model that behaviour on the block copolymer
      surfaces. An increase in the adhesive force of the surface was observed to
      correlate with the adsorption of bovine serum albumin on the block copolymer
      surfaces investigated.

PMID- 21077885
TI  - Gradient based intensity normalization.
AB  - Intensity normalization is important in quantitative image analysis, especially
      when extracting features based on intensity. In automated microscopy,
      particularly in large cellular screening experiments, each image contains objects
      of similar type (e.g. cells) but the object density (number and size of the
      objects) may vary markedly from image to image. Standard intensity normalization
      methods, such as matching the grey-value histogram of an image to a target
      histogram from, i.e. a reference image, only work well if both object type and
      object density are similar in the images to be matched. This is typically not the
      case in cellular screening and many other types of images where object type
      varies little from image to image, but object density may vary dramatically. In
      this paper, we propose an improved form of intensity normalization which uses
      grey-value as well as gradient information. This method is very robust to
      differences in object density. We compare and contrast our method with standard
      histogram normalization across a range of image types, and show that the modified
      procedure performs much better when object density varies between images.

PMID- 21077886
TI  - The role of myosin V in exocytosis and synaptic plasticity.
AB  - In neuroscience, myosin V motor proteins have attracted attention since they are
      highly expressed in brain, and absence of myosin Va in man leads to a severe
      neurological disease called Griscelli syndrome. While in some cells myosin V is
      described to act as a vesicle transport motor, an additional role in exocytosis
      has emerged recently. In neurons, myosin V has been linked to exocytosis of
      secretory vesicles and recycling endosomes. Through these functions, it is
      implied in regulating important brain functions including the release of
      neuropeptides by exocytosis of large dense-core vesicles and the insertion of
      neurotransmitter receptors into post-synaptic membranes. This review focuses on
      the role of myosin V in (i) axonal transport and stimulated exocytosis of large
      dense-core vesicles to regulate the secretion of neuroactive substances, (ii)
      tethering of the endoplasmic reticulum at cerebellar synapses to permit long-term
      depression, (iii) recycling of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA) receptors at hippocampal synapses during long-term
      potentiation, and (iv) recycling of nicotinic acetylcholine receptors at the
      neuromuscular junction. Myosin V is thus discussed as an important modulator of
      synaptic plasticity.

PMID- 21077887
TI  - The sensitivity of tropical leaf litter decomposition to temperature: results
      from a large-scale leaf translocation experiment along an elevation gradient in
      Peruvian forests.
AB  - * We present the results from a litter translocation experiment along a 2800-m
      elevation gradient in Peruvian tropical forests. The understanding of the
      environmental factors controlling litter decomposition is important in the
      description of the carbon and nutrient cycles of tropical ecosystems, and in
      predicting their response to long-term increases in temperature. * Samples of
      litter from 15 species were transplanted across all five sites in the study, and
      decomposition was tracked over 448 d. * Species' type had a large influence on
      the decomposition rate (k), most probably through its influence on leaf quality
      and morphology. When samples were pooled across species and elevations, soil
      temperature explained 95% of the variation in the decomposition rate, but no
      direct relationship was observed with either soil moisture or rainfall. The
      sensitivity of the decay rate to temperature (kappa(T)) varied seven-fold across
      species, between 0.024 and 0.169  degrees C-1, with a mean value of 0.118 +/-
      0.009  degrees C-1 (SE). This is equivalent to a temperature sensitivity
      parameter (Q10) for litter decay of 3.06 +/- 0.28, higher than that frequently
      assumed for heterotrophic processes. * Our results suggest that the warming of
      approx. 0.9  degrees C experienced in the region in recent decades may have
      increased decomposition and nutrient mineralization rates by c. 10%.

PMID- 21077889
TI  - Preparing for tomorrow's challenges.

PMID- 21077888
TI  - A K+ channel from salt-tolerant melon inhibited by Na+.
AB  - * The possible roles of K(+) channels in plant adaptation to high Na(+)
      conditions have not been extensively analyzed. Here, we characterize an inward
      Shaker K(+) channel, MIRK (melon inward rectifying K(+) channel), cloned in a
      salt-tolerant melon (Cucumis melo) cultivar, and show that this channel displays
      an unusual sensitivity to Na(+) . * MIRK expression localization was analyzed by
      reverse-transcription PCR (RT-PCR). MIRK functional analyses were performed in
      yeast (growth tests) and Xenopus oocytes (voltage-clamp). MIRK-type activity was
      revealed in guard cells using the patch-clamp technique. * MIRK is an inwardly
      rectifying Shaker channel belonging to the 'KAT' subgroup and expressed in melon
      leaves (especially in guard cells and vasculature), stems, flowers and fruits.
      Besides having similar features to its close homologs, MIRK displays a unique
      property: inhibition of K(+) transport by external Na(+) . In Xenopus oocytes,
      external Na(+) affected both inward and outward MIRK currents in a voltage
      independent manner, suggesting a blocking site in the channel external mouth. *
      The degree of MIRK inhibition by Na(+) , which is dependent on the Na(+) /K(+)
      concentration ratio, is predicted to have an impact on the control of K(+)
      transport in planta upon salt stress. Expressed in guard cells, MIRK might
      control Na(+) arrival to the shoots via regulation of stomatal aperture by Na(+)
      .

PMID- 21077890
TI  - The future of baccalaureate degrees for nurses.
AB  - PROBLEM.  Unlike other professional healthcare disciplines, the profession of
      nursing has multiple levels of entry. Recently, several states have proposed
      legislation to mandate completion of baccalaureate education after 10 years of
      nursing licensure. METHODS.  This article examines the proposals, statistics,
      strategies, and other relevant literature on baccalaureate education for nurses
      and the positive outcomes associated with a more highly educated nursing
      workforce. FINDINGS.  The proposal recognizes the entry level preparation
      provided by associate degree nurses and is an innovative solution that offers a
      balance between multiple entry levels into practice and continued educational
      preparation. CONCLUSIONS.  Through a combination of the entry level preparation
      of associate degree nurses and baccalaureate education, a stronger nursing
      workforce can be created and patient outcomes and quality of care improved.

PMID- 21077891
TI  - Creative controversy.

PMID- 21077892
TI  - Combat-related blast-induced neurotrauma: a public health problem?
AB  - The purpose of this article is to raise nurses' awareness of the significance and
      potential public health impact of combat-related blast-induced neurotrauma (BINT)
      in U.S. troops returning from Afghanistan and Iraq. A comprehensive review of the
      current literature on BINT was completed by the author, based primarily on combat
      related blast exposure in the military population. She found that it is necessary
      to theorize about potential etiologies for mild traumatic brain injury in the
      military population since the literature suggests that neurological and
      psychological trauma resulting from military duty may be linked to exposure to
      blasts. Identification of potential risk factors for BINT in the military
      population provides direction for scientific inquiry into this emerging
      phenomenon. Gaps in current knowledge and its health implications for future
      scientific study in nursing are presented.

PMID- 21077893
TI  - Said another way: asking the right questions regarding the effectiveness of
      simulations.
AB  - Applying simulations in healthcare practice and education is increasingly
      accepted, yet a number of recent authors have questioned the effectiveness of
      these technologies. The contention is that while high-fidelity simulators may
      contribute to educational gains, their gains compared to low-tech alternatives
      are often "not significant." That assessment, however, and the evidence it is
      based on, may be a consequence of asking the wrong questions. Typical studies
      often compare a measure for "average success" for one group's members versus
      another's on some criteria, but this can mask important information about the
      "tails" of the distribution for how trainees are performing. An alternative
      approach, adapted from quality control, compares error rates for each group in
      the experiment, in aggregate. The statistical results of evaluations can change
      if this method is used, as illustrated by a recent study showing that simulation
      training can significantly reduce the frequency of medication administration
      errors among student nurses on placement. The paper includes a case study to
      tangibly demonstrate how the way we frame our evaluation test question can
      reverse the apparent statistical finding of the significance test.

PMID- 21077894
TI  - Concept analysis of risk in relation to coronary heart disease among Filipino
      Americans.
AB  - PURPOSE: To analyze the concept of risk in relation to coronary heart disease
      (CHD) among Filipino-Americans (FAs) and provide a new definition of risk.
      SOURCE: Published literature. CONCLUSION: This concept analysis provided a new
      meaning of risk in relation to CHD among FAs and shed light on further
      understanding of risk. Risk has been laced with negativity in health care, but
      based on the current literature, risk can be conceptualized in a positive
      perspective, especially in the area of chronic health disease such as CHD.
      However, further research is needed in the conceptualization of risk related to
      CHD for consistency, adequacy, and meaning.

PMID- 21077895
TI  - Teaching research to graduate nursing students: a strategy using clinically based
      research projects.
AB  - This article describes an approach to teaching advanced practice nursing students
      the research process through the application of the research process to clinical
      problems. In the course, students propose solutions to clinically based research
      projects through conceptualizing the problem, identifying an appropriate
      theoretical framework, conceptualizing the intervention or clinical guidelines,
      and designing a project that includes the research design, sampling strategies,
      procedures for implementation of the project, and plans for data collection and
      analysis. These strategies challenge the advanced practice nursing student to
      apply research concepts to problems encountered in clinical practice and
      reinforces the skills needed to critique the literature, to summarize the
      published findings on a problem, to conceptualize a research study, and to
      disseminate their findings in oral presentations.

PMID- 21077896
TI  - Is the DNP the answer to the nursing faculty shortage? Not likely!
AB  - The DNP is being touted as the answer to the faculty shortage. There is no
      evidence that DNP graduates are any more willing to embrace the low salaries of
      nursing faculty than PhD graduates. The idea of the DNP as the answer to the
      faculty shortage is challenged.

PMID- 21077897
TI  - The photochemistry of uracil: a reinvestigation.
AB  - Results from a re-examination of the photochemical reactions undergone by uracil
      (Ura) are presented. Irradiation of Ura in frozen aqueous solution at -78.5
      degrees C produces two diastereomeric (6-4) products, namely the cis and trans
      isomers of 5-hydroxy-6-4'-(pyrimidin-2'-one)-5,6-dihydrouracil. Upon heating in
      0.1m HCl, each of these compounds decomposes to form 6-4'-(pyrimidin-2'
      one)uracil. In addition, evidence for production of a hydrate of a trimer of Ura
      is presented, Irradiation of this compound at 254nm forms Ura and a (6-4) adduct
      as products. The compounds 5-4'-(pyrimidin-2'-one)uracil and 6-hydroxy-5,6
      dihydrouracil were also present after Ura was irradiated in frozen aqueous
      solution. Cyclobutane dimers (CBDs) are formed when Ura is irradiated in the
      frozen aqueous state, in fluid aqueous and acetonitrile solution and in the
      presence of photosensitizers (e.g. acetone). Published information, concerning
      the identity and relative quantitative importance of the four CBD isomers (cis
      syn, cis-anti, trans-syn and trans-anti) formed in these photochemical systems,
      is incomplete and often in substantial disagreement. Using chemical methods in
      conjunction with HPLC, the identity and relative amounts of the four dimers have
      been determined in each of these systems. Consequently, a number of
      inconsistencies found in the literature concerning dimer product identity and
      quantitative distribution have been resolved.

PMID- 21077898
TI  - Characterization of CdHgTe/CdS QDs for near infrared fluorescence imaging of
      spinal column in a mouse model.
AB  - Near infrared (NIR) CdHgTe/CdS quantum dots (QDs) were successfully prepared by a
      green synthetic route. The characteristics such as morphology, size, spectra,
      stability and toxicity were investigated in detail. The fluorescence wavelength
      of CdHgTe/CdS QDs could be adjusted to the NIR range (812nm), which made the in
      vivo NIR imaging possible. The in vivo dynamic biodistribution of CdHgTe/CdS QDs
      in a mouse model was monitored by an NIR imaging system. Results indicated that
      CdHgTe/CdS QDs with a diameter of about 5.8nm targeted to spinal column
      effectively. Further imaging of the dissected spine disclosed that QDs targeted
      to vertebra rather than spinal cord. The high fluorescence intensity together
      with targeting effect makes CdHgTe/CdS QDs particular candidates for imaging
      purposes in experimental animal models of vertebral injury.

PMID- 21077899
TI  - A quantitative comparison of 5-aminolaevulinic acid- and methyl aminolevulinate
      induced fluorescence, photobleaching and pain during photodynamic therapy.
AB  - The characteristics of protoporphyrin IX (PPIX) fluorescence in superficial basal
      cell carcinoma (sBCC) and carcinoma in situ (Bowen's Disease, BD) following
      application of 5-aminolaevulinic acid (5-ALA) and its methyl ester (methyl
      aminolevulinate [MAL]) before, during and after photodynamic therapy (PDT) were
      investigated in 40 patients. Photosensitizer prodrug penetration can limit PDT
      efficacy and understanding the characteristics of PPIX fluorescence through
      fluorescence spectroscopy, may improve knowledge of photosensitizer delivery.
      Fluorescence intensity was assessed quantitatively, and the rate of
      photobleaching was determined by fitting an exponential decay. As a secondary end
      point, PDT-induced pain was also measured continuously during treatment using a
      novel hand-held device, known as a pain logger. In vivo PPIX fluorescence was
      shown to decrease during irradiation, allowing the in vivo photobleaching of PPIX
      to be monitored. No significant difference was found between ALA- or MAL-induced
      PPIX fluorescence in lesions of sBCC and BD (P>0.05), indicating no detectable
      difference in PPIX kinetics for the two prodrugs as assessed by these measures.
      Pain, as assessed by the logger device, showed high interindividual variability
      and pain levels tended to be higher initially, decreasing during treatment. No
      difference was seen in pain experienced during ALA-or MAL-PDT (P>0.05).

PMID- 21077900
TI  - Isolation and characteristics of the PSI-LHCI-LHCII supercomplex under high
      light.
AB  - We developed a novel method for the isolation of the PSI-LHCI-LHCII complex from
      spinach leaves. The supercomplex was resolved into a core complex (CPI), LHCII
      trimers, LHCI dimers and LHCII monomers using green gel electrophoresis. We then
      investigate changes in the fluorescence and absorption spectra of PSI-LHCI-LHCII
      under high light. In addition, we compared light-induced denaturation of the core
      protein subunits in both PSI-LHCI and PSI-LHCI-LHCII. Differences in denaturation
      and photochemical activity indicated that binding of LHCII increased the
      photosensitivity of the PSI core. Increased energy delivered to the PSI core
      during illumination accelerated damage to the core complex.

PMID- 21077901
TI  - Glucose-6-phosphate dehydrogenase-dependent hydrogen peroxide production is
      involved in the regulation of plasma membrane H+-ATPase and Na+/H+ antiporter
      protein in salt-stressed callus from Carex moorcroftii.
AB  - Glucose-6-phosphate dehydrogenase (G6PDH) is important for the activation of
      plant resistance to environmental stresses, and ion homeostasis is the
      physiological foundation for living cells. In this study, we investigated G6PDH
      roles in modulating ion homeostasis under salt stress in Carex moorcroftii
      callus. G6PDH activity increased to its maximum in 100 mM NaCl treatment and
      decreased with further increased NaCl concentrations. K+/Na+ ratio in 100 mM NaCl
      treatment did not exhibit significant difference compared with the control;
      however, in 300 mM NaCl treatment, it decreased. Low-concentration NaCl (100 mM)
      stimulated plasma membrane (PM) H+-ATPase and NADPH oxidase activities as well as
      Na+/H+ antiporter protein expression, whereas high-concentration NaCl (300 mM)
      decreased their activity and expression. When G6PDH activity and expression were
      reduced by glycerol treatments, PM H+-ATPase and NADPH oxidase activities, Na+/H+
      antiporter protein level and K+/Na+ ratio dramatically decreased. Simultaneously,
      NaCl-induced hydrogen peroxide (H2O2) accumulation was abolished. Exogenous
      application of H2O2 increased G6PDH, PM H+-ATPase and NADPH oxidase activities,
      Na+/H+ antiporter protein expression and K+/Na+ ratio in the control and glycerol
      treatments. Diphenylene iodonium (DPI), the NADPH oxidase inhibitor, which
      counteracted NaCl-induced H2O2 accumulation, decreased G6PDH, PM H+-ATPase and
      NADPH oxidase activities, Na+/H+ antiporter protein level and K+/Na+ ratio.
      Western blot result showed that G6PDH expression was stimulated by NaCl and H2O2,
      and blocked by DPI. Taken together, G6PDH is involved in H2O2 accumulation under
      salt stress. H2O2, as a signal, upregulated PM H+-ATPase activity and Na+/H+
      antiporter protein level, which subsequently resulted in the enhanced K+/Na+
      ratio. G6PDH played a central role in the process.

PMID- 21077903
TI  - Hail the impossible: p-values, evidence, and likelihood.
AB  - Significance testing based on p-values is standard in psychological research and
      teaching. Typically, research articles and textbooks present and use p as a
      measure of statistical evidence against the null hypothesis (the Fisherian
      interpretation), although using concepts and tools based on a completely
      different usage of p as a tool for controlling long-term decision errors (the
      Neyman-Pearson interpretation). There are four major problems with using p as a
      measure of evidence and these problems are often overlooked in the domain of
      psychology. First, p is uniformly distributed under the null hypothesis and can
      therefore never indicate evidence for the null. Second, p is conditioned solely
      on the null hypothesis and is therefore unsuited to quantify evidence, because
      evidence is always relative in the sense of being evidence for or against a
      hypothesis relative to another hypothesis. Third, p designates probability of
      obtaining evidence (given the null), rather than strength of evidence. Fourth, p
      depends on unobserved data and subjective intentions and therefore implies, given
      the evidential interpretation, that the evidential strength of observed data
      depends on things that did not happen and subjective intentions. In sum, using p
      in the Fisherian sense as a measure of statistical evidence is deeply
      problematic, both statistically and conceptually, while the Neyman-Pearson
      interpretation is not about evidence at all. In contrast, the likelihood ratio
      escapes the above problems and is recommended as a tool for psychologists to
      represent the statistical evidence conveyed by obtained data relative to two
      hypotheses.

PMID- 21077902
TI  - Epigenetic and physiological effects of gibberellin inhibitors and chemical
      pruners on the floral transition of azalea.
AB  - The ability to control the timing of flowering is a key strategy in planning the
      production of ornamental species such as azaleas; however, it requires a thorough
      understanding of floral transition. DNA methylation is involved in controlling
      the functional state of chromatin and gene expression during floral induction
      pathways in response to environmental and developmental signals. Plant hormone
      signalling is also known to regulate suites of morphogenic processes in plants
      and its role in flowering-time control is starting to emerge as a key controlling
      step. This work investigates if the gibberellin (GA) inhibitors and chemical
      pinching applied in improvement of azalea flowering alter the dynamics of DNA
      methylation or the levels of polyamines (PAs), GAs and cytokinins (CKs) during
      floral transition, and whether these changes could be related to the effects
      observed on flowering ability. DNA methylation during floral transition and
      endogenous content of PAs, GAs and CKs were analysed after the application of GA
      synthesis inhibitors (daminozide, paclobutrazol and chlormequat chloride) and a
      chemical pruner (fatty acids). The application of GA biosynthesis inhibitors
      caused alterations in levels of PAs, GAs and CKs and in global DNA methylation
      levels during floral transition; also, these changes in plant growth regulators
      and DNA methylation were correlated with flower development. DNA methylation, PA,
      GA and CK levels can be used as predictive markers of plant floral capacity in
      azalea.

PMID- 21077904
TI  - Korean deaf adolescents' recognition of written words for taxonomic categories of
      different levels.
AB  - Deaf college students seem to have relatively stronger associations from words
      for taxonomic categories of basic (e.g., snake) to those of super-ordinate (e.g.,
      reptiles) level than vice versa compared with hearing students in word
      association (Marschark, Convertino, McEvoy & Masteller, 2004). In deciding
      whether two sequentially presented words for taxonomic categories of different
      levels are conceptually related, deaf adolescents might therefore have a poorer
      performance when they see a category name before than when they see it after one
      of the corresponding exemplar words. Deaf Korean adolescents were found to
      recognize words for taxonomic categories of super-ordinate level with lower
      efficiencies than those of basic level. Their accuracy seemed to reflect a
      reversed typicality effect when they decided that first-presented words for
      taxonomic categories of basic level were conceptually related to second-presented
      words for those of super-ordinate level. It was argued that deaf Korean
      adolescents went through a temporary stage of having iconic representations of
      several exemplars of the category aroused in working memory before the abstract
      semantic representation was fully activated when they saw the word for a
      taxonomic category of super-ordinate level.

PMID- 21077905
TI  - Stereotype threat in salary negotiations is mediated by reservation salary.
AB  - Women are stereotypically perceived as worse negotiators than men, which may make
      them ask for less salary than men when under stereotype threat (Kray et al.,
      2001). However, the mechanisms of stereotype threat are not yet properly
      understood. The current study investigated whether stereotype threat effects in
      salary negotiations can be explained by motivational factors. A total of 116
      business students negotiated salary with a confederate and were either told that
      this was diagnostic of negotiating ability (threat manipulation) or not. Measures
      of minimum (reservation) and ideal (aspiration) salary goals and regulatory focus
      were collected. The finding (Kray et al., 2001) that women make lower salary
      requests than men when under stereotype threat was replicated. Women in the
      threat condition further reported lower aspiration salary, marginally
      significantly lower reservation salary and less eagerness/more vigilance than
      men. Reservation salary mediated the stereotype threat effect, and there was a
      trend for regulatory focus to mediate the effect. Thus, reservation salary partly
      explains why women ask for less salary than men under stereotype threat. Female
      negotiators may benefit from learning that stereotype threat causes sex
      differences in motivation.

PMID- 21077907
TI  - Susceptibility to hyperosmotic stress-induced phosphatidylserine exposure
      increases during red blood cell storage.
AB  - BACKGROUND: During storage of red blood cell (RBCs) before transfusion, RBCs
      undergo a series of structural and functional changes that include the exposure
      of phosphatidylserine (PS), a potent removal signal. It was postulated that,
      during blood bank storage, the susceptibility to stress-induced PS exposure
      increases, thereby rendering a considerable fraction of the RBCs susceptible to
      rapid removal after transfusion. STUDY DESIGN AND METHODS: RBCs were processed
      and stored following standard Dutch blood bank procedures. Samples were taken
      every week for up to 6 weeks and exposed to various stress conditions, such as
      hyperosmotic shock and energy depletion. The effect of these treatments on PS
      exposure was measured by flow cytometric analysis of annexin V binding. The same
      analyses were performed on RBCs that had been separated according to density
      using discontinuous Percoll gradients. RESULTS: During storage under blood bank
      conditions, RBCs become increasingly susceptible to loss of phospholipid
      asymmetry induced by hyperosmotic shock and energy depletion. Especially the RBCs
      of higher densities, that have a smaller volume and an increased HbA1c content as
      is typical of aged RBCs, become increasingly susceptible with storage time.
      CONCLUSIONS: During storage, RBCs develop an increased susceptibility to stress
      induced loss of phospholipid asymmetry that is especially associated with an
      aging phenotype. This increased susceptibility may be responsible for the rapid
      disappearance of a considerable fraction of the RBCs during the first 24 hours
      after transfusion.

PMID- 21077906
TI  - The relationship between phonological skills and word decoding.
AB  - Word decoding ability is a critical factor in reading performance. In the present
      study, we examined the relationship between word decoding ability and three
      different phonological skills; phonemic awareness, verbal short-term memory (V
      STM), and rapid automatic naming (RAN) in 1007 Scandinavian third- and fifth
      graders. In the first part of the study, we sought to investigate the influence
      of the three phonological skills on word decoding ability. Using multiple
      regression analysis, our result clearly demonstrated that phonemic awareness was
      the most powerful phonological skill explaining variance in word decoding ability
      among average decoders. Among children with poor decoding skills, however, RAN
      was the most important factor in Grade 3, whereas V-STM was the main contributor
      to decoding ability among children in Grade 5. In the second part of the
      research, we examined the relationship between poor phonological skills and word
      decoding ability. Interestingly, our result revealed that approximately one half
      of the children with phonological difficulties, still performed within the
      average range with regard to word decoding ability. However, our analyses
      confirmed earlier research concerning the severe word decoding difficulties
      children with both poor phonemic awareness and restricted V-STM, experience.

PMID- 21077908
TI  - Hospital blood bank information systems accurately reflect patient transfusion:
      results of a validation study.
AB  - BACKGROUND: Hospital transfusion laboratories collect information regarding blood
      transfusion and some registries gather clinical outcomes data without transfusion
      information, providing an opportunity to integrate these two sources to explore
      effects of transfusion on clinical outcomes. However, the use of laboratory
      information system (LIS) data for this purpose has not been validated previously.
      STUDY DESIGN AND METHODS: Validation of LIS data against individual patient
      records was undertaken at two major centers. Data regarding all transfusion
      episodes were analyzed over seven 24-hour periods. RESULTS: Data regarding 596
      units were captured including 399 red blood cell (RBC), 95 platelet (PLT), 72
      plasma, and 30 cryoprecipitate units. They were issued to: inpatient 221 (37.1%),
      intensive care 109 (18.3%), outpatient 95 (15.9%), operating theater 45 (7.6%),
      emergency department 27 (4.5%), and unrecorded 99 (16.6%). All products recorded
      by LIS as issued were documented as transfused to intended patients. Median time
      from issue to transfusion initiation could be calculated for 535 (89.8%)
      components: RBCs 16 minutes (95% confidence interval [CI], 15-18 min;
      interquartile range [IQR], 7-30 min), PLTs 20 minutes (95% CI, 15-22 min; IQR, 10
      37 min), fresh-frozen plasma 33 minutes (95% CI, 14-83 min; IQR, 11-134 min), and
      cryoprecipitate 3 minutes (95% CI, -10 to 42 min; IQR, -15 to 116 min).
      CONCLUSIONS: Across a range of blood component types and destinations comparison
      of LIS data with clinical records demonstrated concordance. The difference
      between LIS timing data and patient clinical records reflects expected time to
      transport, check, and prepare transfusion but does not affect the validity of
      linkage for most research purposes. Linkage of clinical registries with LIS data
      can therefore provide robust information regarding individual patient
      transfusion. This enables analysis of joint data sets to determine the impact of
      transfusion on clinical outcomes.

PMID- 21077909
TI  - Absence of detectable xenotropic murine leukemia virus-related virus in plasma or
      peripheral blood mononuclear cells of human immunodeficiency virus type 1
      infected blood donors or individuals in Africa.
AB  - BACKGROUND: Since the identification of xenotropic murine leukemia virus-related
      virus (XMRV) in prostate cancer patients in 2006 and in chronic fatigue syndrome
      patients in 2009, conflicting findings have been reported regarding its etiologic
      role in human diseases and prevalence in general populations. In this study, we
      screened both plasma and peripheral blood mononuclear cells (PBMNCs) collected in
      Africa from blood donors and human immunodeficiency virus Type 1 (HIV-1)-infected
      individuals to gain evidence of XMRV infection in this geographic region. STUDY
      DESIGN AND METHODS: A total of 199 plasma samples, 19 PBMNC samples, and 50
      culture supernatants from PBMNCs of blood donors from Cameroon found to be
      infected with HIV-1 and HIV-1 patients from Uganda were screened for XMRV
      infection using a sensitive nested polymerase chain reaction (PCR) or reverse
      transcription (RT)-PCR assay. RESULTS: Using highly sensitive nested PCR or RT
      PCR and real-time PCR assays capable of detecting at least 10 copies of XMRV
      plasmid DNA per reaction, none of the 268 samples tested were found to be XMRV
      DNA or RNA positive. CONCLUSIONS: Our results failed to demonstrate the presence
      of XMRV infection in African blood donors or individuals infected with HIV-1.
      More studies are needed to understand the prevalence, epidemiology, and
      geographic distribution of XMRV infection worldwide.

PMID- 21077910
TI  - Fanconi syndrome in a patient with beta-thalassemia major after using deferasirox
      for 27 months.
AB  - BACKGROUND: Deferasirox (DFRA) is a new approved oral iron chelator. Its
      advantages are that it is convenient and better tolerated and adhered to due to
      "once-daily" oral dosage. However, its use in the field is limited and it is yet
      to be subjected to postmarketing surveillance. CASE REPORT: A 18.75-year-old male
      with beta-thalassemia major received oral DFRA therapy due to transfusional iron
      overload for 27 months. He had received iron chelation therapy with deferoxamine
      injection together with oral deferiprone. However, his compliance was poor (very
      high routine serum ferritin level, ranging from 1059 to 6030 ng/mL). After 25
      months of DFRA therapy, the serum ferritin level declined from 4097 to 1343
      ng/mL. He experienced five hospital admissions including coma, Fanconi syndrome,
      hepatic dysfunction, and thrombocytopenia after using DFRA as oral iron chelator.
      After we discontinued DFRA, he recovered fully without hepatic dysfunction,
      thrombocytopenia, proteinuria, glucosuria, and hypophosphatemia. CONCLUSIONS: Our
      case illustrates the potential risks of DFRA-induced renal toxicity, hepatic
      dysfunction, and thrombocytopenia. Meticulous monitoring of kidney, liver, and
      hematopoietic function is mandatory for patients undergoing treatment with DFRA.
      Further investigation of the potential risk and adverse effects of long-term DFRA
      use is necessary.

PMID- 21077912
TI  - Use of cryoablation for treatment of tachyarrhythmias in 2010: survey of current
      practices of pediatric electrophysiologists.
AB  - BACKGROUND: Cryoablation for arrhythmia substrates in pediatrics has been
      available since 2003. The purpose of this study was to evaluate the current
      approach of pediatric electrophysiologists to the use of cryoablation in the
      current era. METHODS: We sent an Internet link to an online survey to all members
      of the Pediatric and Congenital Electrophysiology Society. Individuals and not
      institutions were surveyed. RESULTS: A total of 70 responses were received.
      Responding physicians were largely invasive pediatric electrophysiologists (94%)
      who practice at mid- to high-volume centers (>50 ablation procedures/year).
      Survey responders report that cryoablation was utilized for <50% of the ablation
      volume, and most utilize it for only 10%. With respect to specific arrhythmia
      substrates, 41% of responders use cryoablation as first-line therapy for
      atrioventricular nodal reentrant tachycardia. For accessory pathways, 94% report
      that cryoablation would only be utilized after mapping the accessory pathway to a
      "high-risk location." Other arrhythmia substrates considered for cryoablation
      would be accessory pathways mapped to high-risk areas, junctional ectopic
      tachycardia, a parahisian ectopic atrial tachycardia, or an atrial tachycardia
      near the phrenic nerve. CONCLUSION: For pediatric electrophysiologists who
      responded to the survey, radiofrequency energy remains the primary energy source
      for ablation. The current use of cryoablation technology is directed at
      arrhythmia substrates near the normal conduction system or other "high-risk"
      areas.

PMID- 21077913
TI  - Hypothyroid patient with Brugada electrocardiographic waveforms: case report.
AB  - We report a 46-year-old man who presented with hypothyroidism. An
      electrocardiogram obtained at the time of the first examination revealed Brugada
      electrocardiographic (Brugada-ECG) waveforms in leads V1 to V3. The patient and
      his family had no history of arrhythmia and syncopal attack. The Brugada-ECG
      waveforms disappeared with the normalization of thyroid function. The case
      suggested that hypothyroidism could lead to secondary Brugada-ECG waveforms
      because of its effect on myocardial ion channels.

PMID- 21077911
TI  - Bacterial growth kinetics in ACD-A apheresis platelets: comparison of plasma and
      PAS III storage.
AB  - BACKGROUND: Our objective was to determine the growth kinetics of bacteria in
      leukoreduced apheresis platelets (LR-AP) in a platelet (PLT) additive solution
      (PAS; InterSol, Fenwal, Inc.) compared to LR-AP stored in plasma. STUDY DESIGN
      AND METHODS: Hyperconcentrated, double-dose LR-AP were collected from healthy
      donors with a separator (AMICUS, Fenwal, Inc.). LR-AP were evenly divided,
      InterSol was added to half (65% InterSol:35% plasma [PAS]), and PLTs in
      autologous plasma were used for a paired control (PL). Bacteria were inoculated
      into each LR-AP PAS/PL pair (0.5-1.6 colony-forming units [CFUs]/mL), and
      bacterial growth was followed for up to 7 days. Time to the end of the lag phase,
      doubling times, maximum concentration (conc-max), and time to maximum
      concentration (time-max) were estimated. RESULTS: Streptococcus viridans did not
      grow to detectable levels in either PAS or PL units. The other bacteria had no
      significant overall difference in the conc-max (p = 0.47) or time-max (p = 0.7)
      between PL and PAS LR-AP; PL had a 0.14 hours faster doubling rate (p = 0.023);
      and PAS had a 4.7 hours shorter lag time (p = 0.016). CONCLUSION: We observed
      that five index organisms will grow in LR-AP stored in a 35%:65% ratio of plasma
      to InterSol where initial bacterial concentrations are 0.5 to 1.6 CFUs/mL. The
      more rapid initiation of log-phase growth for bacteria within a PAS storage
      environment resulted in a bacterial concentration up to 4 logs higher in the PAS
      units compared to the plasma units at 24 hours, but with no difference in the
      conc-max. This may present an early bacterial detection advantage for PAS-stored
      PLTs.

PMID- 21077914
TI  - Symptomatic sinus tachycardia with perpetuating slow pathway: successful
      treatment with radiofrequency ablation.
AB  - We report a case of sinus tachycardia with perpetuating slow pathway (SP)
      conduction in a 42-year-old woman who developed severe symptoms as a result of
      atrioventricular (AV) desynchronization. The restoration of an AV synchrony,
      achieved with selective radiofrequency ablation of the SP, eliminated the
      symptomatic arrhythmia and may represent a reasonable therapeutic option despite
      the fact that the patient has no AV-node reentrant tachycardia. This case
      demonstrates the importance of AV timing. 

PMID- 21077915
TI  - Recollection of pain due to inappropriate versus appropriate implantable
      cardioverter-defibrillator shocks.
AB  - BACKGROUND: Although inappropriate shocks are known to be an important
      consequence of implantable cardioverter-defibrillators (ICDs), the subjective
      experience of pain intensity perceived by those receiving inappropriate versus
      appropriate shocks has not previously been examined. METHODS: One hundred ICD
      patients underwent a standardized interview by an investigator blinded to the
      clinical history. Patients with a previous ICD shock were asked to describe the
      intensity of the associated pain on a standard 0-10 scale (10 being the worst
      pain they had ever experienced). Medical charts were then examined for any
      history of inappropriate and/or appropriate ICD discharges. RESULTS: Thirty-five
      of the 100 patients had a record of at least one ICD shock, and 17 had
      experienced at least one inappropriate shock. Those with a history of an
      inappropriate shock described a significantly higher median pain scale (9,
      interquartile range [IQR] 8-10) compared to those with a history of only
      appropriate shocks (median 4, IQR 2-8, P = 0.0011). In multivariable analysis, a
      history of an inappropriate shock was the only predictor statistically
      significantly associated with an increase in shock pain: the pain scale for those
      with inappropriate shocks was higher by 2.8 points on average after multivariable
      adjustment (95% confidence interval 0.29-5, P = 0.030). Eighteen patients had
      considered having their device deactivated, and a history of an inappropriate
      shock was the only factor independently associated with this consideration.
      CONCLUSIONS: Compared to those who have received only appropriate shocks,
      inappropriate ICD shocks are associated with a recollection of greater pain and
      consideration of device inactivation.

PMID- 21077916
TI  - Effect of a collateral ligament sparing surgical approach on mechanical
      properties of equine proximal interphalangeal joint arthrodesis constructs.
AB  - OBJECTIVE: To (1) compare the effect of a collateral ligament sparing surgical
      approach with an open surgical approach on mechanical properties of proximal
      interphalangeal joint (PIPJ) arthrodesis, and (2) to determine the percentage of
      articular cartilage surface removed by transarticular (TA) drilling with
      different diameter drill bits. STUDY DESIGN: Randomized paired limb design.
      SAMPLE POPULATION: Cadaveric equine limbs (n=76). METHODS: Cadaveric PIPJ were
      drilled using a 3.5, 4.5, or 5.5 mm drill bit at 80-84 degrees  to the dorsal
      plane to remove articular cartilage and subchondral bone from the distal
      articular surface of the proximal phalanx (P1) and the proximal articular surface
      of the middle phalanx (P2). Bone ends were photographed and the percentage of the
      projected surface area that was denuded of cartilage was measured. PIPJ
      arthrodesis constructs (3-hole dynamic compression plate [DCP], two 5.5 mm TA
      screws inserted in lag fashion, medial and lateral to the DCP; DCP-TA) were
      created using 2 surgical approaches in paired limbs. A conventional open approach
      was used in 1 limb and a collateral ligament sparing approach used in the other
      limb. Constructs were tested to failure in single-cycle 3-point
      dorsopalmar/plantar or lateromedial bending. Maximum load, yield load, and
      composite stiffness were compared between techniques. RESULTS: The 3.5, 4.5, and
      5.5 mm drill bits removed 24+/-4%, 35+/-5%, and 45+/-7% of total PIPJ articular
      cartilage surface, respectively. Constructs with the collateral ligament sparing
      approach had significantly greater mean yield load (11.3+/-2.8 versus 7.68+/-1.1
      kN, P=.008) and mean maximum load (13.5+/-3.1 versus 10.1+/-1.94 kN, P=.02) under
      lateromedial bending. Under dorsopalmar/plantar bending there was no significant
      difference between surgical approaches. The collateral ligament sparing
      arthrodesis technique had a shorter surgical time (19+/-3 minutes) compared with
      the open technique (31+/-3 minutes). CONCLUSION: A collateral ligament sparing
      surgical approach to the PIPJ with removal of articular cartilage by TA drilling
      and arthrodesis by DCP-TA was faster and stronger in mediolateral bending than
      arthrodesis constructs created with an open surgical approach. CLINICAL
      RELEVANCE: Preservation of the collateral ligaments and TA drilling for cartilage
      removal during PIPJ arthrodesis may be a superior approach to the conventional
      open approach and warrants clinical evaluation.

PMID- 21077917
TI  - Exercising videoendoscopic evaluation of 45 horses with respiratory noise and/or
      poor performance after laryngoplasty.
AB  - OBJECTIVE: To (1) assess upper airway function by videoendoscopy in horses
      performing poorly after laryngoplasty and (2) establish whether dynamic collapse
      of the left arytenoid can be predicted by the degree of resting postsurgical
      abduction. STUDY DESIGN: Case series. ANIMALS: Horses that had left laryngoplasty
      (n=45). METHODS: Medical records (June 1993-December 2007) of horses evaluated
      for abnormal respiratory noise and/or poor performance after laryngoplasty were
      reviewed. Horses with video recordings of resting and exercising upper airway
      endoscopy were included and postsurgical abduction categorized. Horses with
      immediate postoperative endoscopy recordings were also evaluated and postsurgical
      abduction categorized. Relationships between resting postsurgical abduction and
      historical information with exercising endoscopic findings were examined.
      RESULTS: Dynamic collapse of the left arytenoid cartilage was probable in horses
      with no postsurgical abduction and could not be predicted in horses with grade 3
      or 4 postsurgical abduction. Respiratory noise was associated with upper airway
      obstruction but was not specific for arytenoid collapse. Most horses with a left
      vocal fold had billowing of the fold during exercise. Other forms of dynamic
      collapse involved the right vocal fold, aryepiglottic folds, corniculate process
      of left arytenoid cartilage, dorsal displacement of soft palate, and pharyngeal
      collapse. Complex obstructions were observed in most examinations and in all
      horses with exercising collapse of the left arytenoid cartilage. CONCLUSIONS:
      There was no relationship between exercising collapse of the left arytenoid
      cartilage and grade 3 or 4 postsurgical abduction but was likely in horses with
      no abduction.

PMID- 21077918
TI  - Partial lateral corpectomy of the thoracolumbar spine in 51 dogs: assessment of
      slot morphometry and spinal cord decompression.
AB  - OBJECTIVE: To report slot morphometry, degree of spinal decompression, and
      factors influencing decompression after partial lateral corpectomy (PLC) of the
      thoracolumbar spine in dogs with intervertebral disc disease. STUDY DESIGN: Case
      series. ANIMALS: Dogs (n=51) with predominantly ventrally located spinal cord
      compression. METHODS: PLC (n=60) were performed. Spinal cord compression was
      determined by computed tomographic (CT) myelography (n=46), myelography (n=2) or
      magnetic resonance imaging (n=3). Postsurgical CT images were used to evaluate
      slot dimensions and orientation, and spinal cord decompression. The influence of
      age, body weight, breed, breed type (chondrodystrophic, nonchondrodystrophic),
      disc location, lateralization and mineralization, presurgical compression, slot
      morphometry, and surgeon on degree of decompression were evaluated. RESULTS: Mean
      slot depth was 64.1% of vertebral body width; mean height, 43.0% of vertebral
      body height; mean cranial extension, 29.5%; median caudal extension, 22.0%
      vertebral body length; mean angulation from horizontal, 6.3 degrees .
      Decompression was satisfactory in 90% of sites after PLC (58% complete, 32%
      good). None of the analyzed factors significantly influenced decompression. All
      lumbar spine PLC resulted in complete or good decompression compared with 83%
      after thoracic PLC (P=.052). Deeper slots tended to allow more complete
      decompression (P=.058). CONCLUSIONS: Thoracolumbar PLC results in satisfactory
      decompression in most cases with a better outcome in the lumbar spine than the
      thoracic spine. Achieving a slot depth equal to 2/3 of vertebral body width might
      facilitate complete decompression.

PMID- 21077919
TI  - Computed tomography to identify preoperative guidelines for internal fixation of
      the distal sesamoid bone in horses: an in vitro study.
AB  - OBJECTIVE: To assess the reliability of computed tomography (CT) to identify the
      direction of implant insertion for cortical screws along the longitudinal axis of
      intact (nonfractured) distal sesamoid bones. STUDY DESIGN: In vitro study. SAMPLE
      POPULATION: Cadaveric paired equine forelimbs (n=16). METHODS: Insertion of a
      cortical screw in lag fashion along the longitudinal axis of intact
      (nonfractured) distal sesamoid bones was evaluated in 2 groups (3.5 and 4.5 mm)
      of 8 paired limbs. In each group, the direction of the distal sesamoid bone was
      determined by CT (Equine XTC 3000 pQCT scanner). Screw placement was verified by
      specimen dissection. Implant direction was considered satisfactory if the entire
      screw length was within the distal sesamoid bone and not damaging the articular
      or flexural surfaces. RESULTS: In our sample and according to our criteria, the
      proportion of satisfactory direction of screws was 0.63 (5/8) for 4.5 mm
      implants, and 0.87 (7/8) for 3.5 mm implants. CONCLUSIONS: CT is a useful imaging
      modality to identify anatomic landmarks for insertion of a 3.5 mm cortical screw
      in the distal sesamoid bone.

PMID- 21077921
TI  - Use of the cumulative summation technique to quantitatively assess a surgical
      learning curve: canine total hip replacement.
AB  - OBJECTIVE: To quantitatively assess a surgical "learning curve" using the
      cumulative summation (CUSUM) score technique. STUDY DESIGN: Application of a
      CUSUM technique to a consecutive series of surgical cases. ANIMALS: Consecutive
      primary cemented total hip replacement (THR; n=116) in 106 dogs. METHODS: Records
      of all dogs that had primary canine THR were reviewed. Data retrieved included
      date of surgery, postoperative complications, and duration of follow-up. The 12
      week outcome was analyzed graphically and with a CUSUM technique. RESULTS: One
      hundred and one (87%) procedures were "successful" and 15 (13%) developed major
      complications within 12 weeks (failures). The CUSUM chart clearly demonstrated an
      initial "learning curve" of ~44 THR. CONCLUSION: The CUSUM technique can be used
      to demonstrate the learning curve for canine THR surgery.

PMID- 21077920
TI  - Increased cartilage oligomeric matrix protein concentrations in equine digital
      flexor tendon sheath synovial fluid predicts intrathecal tendon damage.
AB  - OBJECTIVES: To evaluate digital flexor tendon sheath (DFTS) synovial fluid
      cartilage oligomeric matrix protein (COMP) concentrations as a molecular marker
      for intrathecal pathology. STUDY DESIGN: Case control study. ANIMALS: Horses
      (n=46) with DFTS tenosynovitis; 23 fresh cadaver horses. METHODS: DFTS synovial
      fluid samples were collected from clinical cases with noninfected DFTS
      tenosynovitis and from control DFTS. Clinical and surgical findings were
      recorded, and dissection of control limbs was performed to confirm the DFTS to be
      grossly normal. Synovial fluid COMP was quantified using a homologous competitive
      inhibition ELISA. RESULTS: Abnormalities were identified tenoscopically:
      intrathecal tendon/ligament tearing was identified in 37 cases and 9 had other
      lesions. In control horses, synovial fluid COMP was higher in younger horses.
      Clinical cases with intrathecal tendon/ligament tearing had higher synovial fluid
      COMP than either clinical cases with other lesions, or controls. In horses >=5
      years old, the sensitivity and specificity of the assay was high for diagnosing
      intrathecal tendon/ligament tearing. CONCLUSIONS: COMP concentrations in DFTS
      synovial fluid were significantly greater than those in normal horses with
      noninfected tenosynovitis caused by intrathecal tendon/ligament tearing, but not
      by other lesions.

PMID- 21077922
TI  - Conversion from diagnostic laparoscopy to laparotomy: risk factors and
      occurrence.
AB  - OBJECTIVE: To determine reasons for conversion from diagnostic laparoscopic
      procedures to celiotomy in dogs and cats. STUDY DESIGN: Case series. ANIMALS:
      Dogs (n=54), cats (40). METHODS: Medical records (2004-2008) were reviewed for
      dogs and cats that had diagnostic laparoscopic or laparoscopic-assisted biopsy.
      Numbers of conversions to laparotomy were recorded, including cause and type
      (elective versus emergent), postoperative complications, and short-term outcome.
      Specific risk factors for conversion, including signalment, preoperative
      diagnostics, and surgical findings were assessed; categorical variables were
      tested by chi(2) and Fisher's exact tests; continuous variables by Student's t
      test and Wilcoxon's rank-sum tests; multivariate logistic regression models were
      created. RESULTS: Twenty animals (21%) had laparoscopic conversion; 13 (65%) were
      considered elective and 7 (35%) emergent conversions. There was no significant
      difference between animals requiring and those not requiring conversion for age,
      weight, sex, body condition score, clinical signs, previous abdominal surgery, or
      surgeon experience. Significant risk factors for conversion included low total
      solids (P=.03), presence of a solitary liver tumor (P<.01), and diagnosis of
      neoplasia (P<.01). CONCLUSIONS: A conversion rate of 21% was found in this
      population of dogs and cats undergoing laparoscopic diagnostic procedures. A
      preoperative finding of a solitary liver tumor, low total solids, and diagnosis
      of malignancy were all significant risk factors for conversion.

PMID- 21077923
TI  - Canine sacroiliac luxation: anatomic study of the craniocaudal articular surface
      angulation of the sacrum to define a safe corridor in the dorsal plane for
      placement of screws used for fixation in lag fashion.
AB  - OBJECTIVE: To define a safe corridor in the dorsal plane relative to the
      articular surface for placement of a single screw in lag fashion to achieve
      stabilization of sacroiliac luxation in the dog. STUDY DESIGN: Cadaveric study.
      METHODS: Dorsoventral radiographs of denuded canine sacra (n=49) were taken to
      determine the safe corridor in the craniocaudal plane, and the maximum, optimum
      and minimum angles were calculated that would allow a screw inserted in lag
      fashion to engage at least 60% of the width of the sacral body without cranial or
      caudal penetration through the bone. RESULTS: The mean safe corridor in the
      dorsal plane is ~24 degrees  wide. Mean craniocaudal minimum, optimum and maximum
      drill angles from the drill start point were 88 degrees , 100 degrees , and 111
      degrees  from the articular surface, respectively. No single angle will
      completely avoid risk of screw penetration beyond the safe corridor cranially and
      caudally. CONCLUSIONS: There is sufficient anatomic variation between different
      canine sacra that a single angle cannot be recommended for screw placement in the
      dorsal plane. CLINICAL RELEVANCE: A standard angle cannot be recommended for
      screw placement in lag fashion within the canine sacrum in the dorsal plane.
      Because of the narrow width of the safe corridor, preoperative measurements on
      radiographs are recommended and a range of angled drill guides may be useful to
      decrease surgeon margin of error.

PMID- 21077924
TI  - Geometric morphometrics and ecological niche modelling for delimitation of near
      sibling triatomine species.
AB  - Identifying morphologically similar triatomine species is key to Chagas' disease
      vector control and surveillance, but remains challenging when only qualitative
      phenotypic data are available. We investigated whether morphometric and
      ecological variation can provide additional criteria for species delimitation by
      combining geometric morphometrics and ecological niche modelling to characterize
      two near-sibling triatomine species, Triatoma sordida and Triatoma garciabesi
      (Reduviidae: Triatominae). We analysed size and shape variation in 231 wings and
      123 heads from one T. garciabesi and three T. sordida populations. Predicted
      distribution maps (21 climatic variables, 324 vector occurrence points) were
      produced using the Maxent method. Multivariate analyses summarized morphological
      and ecological variation. Wings and heads of T. sordida were significantly larger
      and more elongated than those of T. garciabesi. Discriminant analyses separated
      the species, with a partial overlap between Argentinean populations. The
      predicted distribution of T. garciabesi included northwest Argentina (mainly arid
      Chaco), whereas that of T. sordida included northeast Argentina (humid Chaco) and
      the Brazilian Cerrado and Caatinga ecoregions. Clear ecological niche differences
      were observed, with T. garciabesi occupying colder and drier areas than T.
      sordida. Our results show how morphometric variation and niche divergence can be
      used to enhance operational criteria for the delimitation of phenotypically
      similar triatomine species.

PMID- 21077925
TI  - Assessment and application of national environmental databases and mapping tools
      at the local level to two community case studies.
AB  - Communities are concerned over pollution levels and seek methods to
      systematically identify and prioritize the environmental stressors in their
      communities. Geographic information system (GIS) maps of environmental
      information can be useful tools for communities in their assessment of
      environmental-pollution-related risks. Databases and mapping tools that supply
      community-level estimates of ambient concentrations of hazardous pollutants,
      risk, and potential health impacts can provide relevant information for
      communities to understand, identify, and prioritize potential exposures and risk
      from multiple sources. An assessment of existing databases and mapping tools was
      conducted as part of this study to explore the utility of publicly available
      databases, and three of these databases were selected for use in a community
      level GIS mapping application. Queried data from the U.S. EPA's National-Scale
      Air Toxics Assessment, Air Quality System, and National Emissions Inventory were
      mapped at the appropriate spatial and temporal resolutions for identifying risks
      of exposure to air pollutants in two communities. The maps combine monitored and
      model-simulated pollutant and health risk estimates, along with local survey
      results, to assist communities with the identification of potential exposure
      sources and pollution hot spots. Findings from this case study analysis will
      provide information to advance the development of new tools to assist communities
      with environmental risk assessments and hazard prioritization.

PMID- 21077926
TI  - On some recent definitions and analysis frameworks for risk, vulnerability, and
      resilience.
AB  - Recently, considerable attention has been paid to a systems-based approach to
      risk, vulnerability, and resilience analysis. It is argued that risk,
      vulnerability, and resilience are inherently and fundamentally functions of the
      states of the system and its environment. Vulnerability is defined as the
      manifestation of the inherent states of the system that can be subjected to a
      natural hazard or be exploited to adversely affect that system, whereas
      resilience is defined as the ability of the system to withstand a major
      disruption within acceptable degradation parameters and to recover within an
      acceptable time, and composite costs, and risks. Risk, on the other hand, is
      probability based, defined by the probability and severity of adverse effects
      (i.e., the consequences). In this article, we look more closely into this
      approach. It is observed that the key concepts are inconsistent in the sense that
      the uncertainty (probability) dimension is included for the risk definition but
      not for vulnerability and resilience. In the article, we question the rationale
      for this inconsistency. The suggested approach is compared with an alternative
      framework that provides a logically defined structure for risk, vulnerability,
      and resilience, where all three concepts are incorporating the uncertainty
      (probability) dimension.

PMID- 21077927
TI  - A social-cognitive model of pandemic influenza H1N1 risk perception and
      recommended behaviors in Italy.
AB  - The outbreak of the pandemic influenza H1N1 2009 (swine flu) between March and
      April 2009 challenged the health services around the world. Indeed,
      misconceptions and worries have led the public to refuse to comply with
      precautionary measures. Moreover, there have been limited efforts to develop
      models incorporating cognitive, social-contextual, and affective factors as
      predictors of compliance with recommended behaviors. The aim of this study was to
      apply a social-cognitive model of risk perception and individual response to
      pandemic influenza H1N1 in a representative sample of Italian population. A
      sample of 1,010 Italians of at least 18 years of age took part in a telephone
      survey. The survey included measures of perceived preparedness of institutions,
      family members and friends' levels of worry, exposure to media campaigns (social
      contextual factors), perceived coping efficacy, likelihood of infection,
      perceived seriousness, personal impact, and severity of illness (cognitive
      evaluations), affective response and compliance with recommended behaviors.
      Results demonstrated that affective response fully mediated the relationship
      between cognitive evaluations and social-contextual factors (with the exception
      of exposure to media campaigns) and compliance with recommended behaviors.
      Perceived coping efficacy and preparedness of institutions were not related to
      compliance with recommended behaviors.

PMID- 21077928
TI  - Wound care by district nurses at primary healthcare centres: a challenging task
      without authority or resources.
AB  - There is a lack of studies that describes how district nurses experience the care
      they provide in connection with wound care. The aim of this study was therefore
      to describe district nurses experiences of their nursing actions when treating
      patients with different kinds of wounds at primary healthcare centres and in the
      home care in order to increase understanding of this kind of care. A qualitative,
      descriptive study was conducted, with interviews of eight district nurses. Data
      were analysed using qualitative content analysis. Three themes and nine sub
      themes were identified. The first theme included two sub-themes which revealed
      that in performing wound care district nurses feel responsible for administering
      wound care, and they feel confident in making independent assessments. The second
      theme included three sub-themes which revealed that district nurses endeavour to
      assess all aspects of their patient's situation and to maintain continuity in
      both their contact with the patient and the treatment. A treatment plan for wound
      care and regular reports were identified as being important in collaboration with
      other healthcare professionals. District nurses wanted their own procedure for
      referral to facilitate the patient's direct contact with a dermatologist. The
      third theme included four sub-themes which revealed difficulties associated with
      ambiguous organisation. Lack of time led to the dressing of wounds being
      delegated to nursing assistants. Limited access to treatment rooms and equipment
      made wound care difficult and inefficient. Wound care in the home care was
      regarded as challenging due to the lack of equipment, and poor lighting,
      ergonomics and hygiene. The results of this study thus identified the aspirations
      of district nurses to provide expert wound care while working independently.
      However, these aspirations were aggravated by organisational shortcomings, such
      as a lack of authority and the resources required to carry out their nursing
      actions optimally.

PMID- 21077929
TI  - Effects of a patient/family-centered practice change on the quality and cost of
      intensive care: research protocol.
AB  - AIM: This paper is a description of a protocol for studying the impact of a
      patient/family-centered, evidence-based practice change on the quality, cost and
      use of services for critically ill patients at the end of life. BACKGROUND:
      International attention currently is focused on the quality and cost/use of
      intensive care services. Empirical literature and expert opinion suggest that
      early, enhanced communication among the clinical team and the patient and family
      results in higher quality and less costly care at the end of life. DESIGN: Our
      Medical Intensive Care Unit practice change involves three components: teaching
      sessions for all Registered Nurses and physicians assigned to the unit;
      patient/family meetings held in 72 hours of the patient's admission to the unit;
      and formal documentation to support communication among clinicians. Ethical
      approval was obtained in April 2009. A two-group post-test design is used, with
      one group comprising patients hospitalized before the practice change and their
      families, and the second group of patients/families after the practice change.
      Data comprise medical record information and families' responses to surveys.
      Final analytic models will result from multivariable regression techniques.
      DISCUSSION: The study represents translational research in that interventions are
      brought to the bedside to reach the people for whom the interventions were
      designed. The practice change is likely to endure after the study because our
      research team is composed of both clinicians and scientists. Also, direct care
      clinicians endorse and are responsible for the practice change.

PMID- 21077930
TI  - Group exercise mode and health-related quality of life among healthy adults.
AB  - AIM: This paper is a report of a study conducted to identify the difference
      between mode of group exercise and health-related quality of life (HRQOL), to
      determine the associations between mode of group exercise chosen by participants
      and their demographic characteristics, and to identify themes from narrative
      comments for each group exercise modality. BACKGROUND: Regular exercise has been
      shown to improve HRQOL in the general population. However, few studies have
      compared mode of exercise--Pilates, step aerobics, and strength training--and
      their impact on HRQOL. METHOD: A comparison was conducted in 2009 between three
      groups of participants who met regularly at a fitness facility. The English
      version of the RAND 36-Item Health Survey (SF-36) was used to collect data. One
      open-ended question was analysed by content analysis. RESULTS: In total, 143
      adults participated in the study. There was a statistically significant
      association between mode of exercise and length of time the participants had been
      exercising (chi(2)=33.42, d.f.=4, P<0.001). There was a statistically significant
      difference in the Energy/Fatigue domain of the SF-36 between two modes of
      exercise: Strength Training and Pilates (z=-2.67, d.f.=2, P=0.008). Qualitative
      data revealed two themes that motivated healthy behaviours: personal, and
      interpersonal. CONCLUSION: Modes of group exercise influence HRQOL domains among
      adults. Healthcare providers need to understand what mode of exercise people are
      participating in order to educate them to achieve a better quality of life and to
      motivate those who are inactive.

PMID- 21077931
TI  - Stress, coping and satisfaction in nursing students.
AB  - AIM: This article is a report of a study conducted to explore the relationship
      between sources of stress and psychological well-being and to consider how
      different sources of stress and coping resources might function as moderators and
      mediators on well-being. BACKGROUND: In most research exploring sources of stress
      and coping in nursing students, stress has been construed as psychological
      distress. Sources of stress likely to enhance well-being and, by implication,
      learning have not been considered. METHOD: A questionnaire was administered to
      171 final year nursing students in 2008. Questions were asked to measure sources
      of stress when rated as likely to contribute to distress (a hassle) and rated as
      likely to help one achieve (an uplift). Support, control, self-efficacy and
      coping style were also measured, along with their potential moderating and
      mediating effects on well-being, operationalized using the General Health
      Questionnaire and measures of course and career satisfaction. FINDINGS: Sources
      of stress likely to lead to distress were more often predictors of well-being
      than were sources of stress likely to lead to positive, eustress states, with the
      exception of clinical placement demands. Self-efficacy, dispositional control and
      support were important predictors, and avoidance coping was the strongest
      predictor of adverse well-being. Approach coping was not a predictor of well
      being. The mere presence of support appeared beneficial as well as the utility of
      that support to help a student cope. CONCLUSION: Initiatives to promote support
      and self-efficacy are likely to have immediate benefits for student well-being.
      In course reviews, nurse educators need to consider how students' experiences
      might contribute not just to potential distress, but to eustress as well.

PMID- 21077932
TI  - Lifestyle advice for Korean Americans and native Koreans with hypertension.
AB  - AIM: This paper is a report of a comparison of advice on lifestyle given by
      healthcare providers and subsequent action by recipients between Korean Americans
      and native Koreans with hypertension. BACKGROUND: High blood pressure is
      controllable by having a healthy lifestyle, such as weight control, dietary
      change, exercise, low-sodium diet, alcohol restriction and smoking cessation, and
      by taking medication. Healthcare providers play an important role in teaching
      individuals with hypertension on healthy lifestyles. METHOD: This descriptive
      comparative study was conducted with a convenience sample of 100 Korean Americans
      and 100 native Koreans with hypertension. They were interviewed between May 2003
      and June 2004 on the advice they received from healthcare providers on lifestyle
      and their subsequent action in terms of taking medication, weight control,
      dietary change, exercise, low-sodium diet, smoking cessation, alcohol restriction
      and tension reduction. Nutrient profiles were examined using the 24-hour dietary
      recall method. FINDINGS: Korean Americans received advice on lifestyle less than
      did native Koreans, but more Korean Americans followed healthy lifestyle advice
      on dietary change and exercise than did native Koreans (P<0.001). Weight control
      was the least adhered to behaviour among the Korean Americans, although almost
      two-thirds of them were overweight or obese. Both groups exceeded the Dietary
      Reference Intakes of sodium, but perceived their sodium consumption as low.
      CONCLUSION: Native Korean participants need to pay closer attention to carrying
      out the advice, whereas healthcare providers to Korean Americans need to give
      more advice on culturally acceptable healthy lifestyles, particularly on dietary
      changes and weight control. Both groups need to monitor their sodium intake more
      realistically. It is not only advice from healthcare providers that is integral
      to control of hypertension, but also that patients should follow that advice.

PMID- 21077933
TI  - Reconciling work and family caregiving among adult-child family caregivers of
      older people with dementia: effects on role strain and depressive symptoms.
AB  - AIMS: This paper is a report of a study that examined the effects of work
      demands, including employment status, work inflexibility and difficulty
      reconciling work and family caregiving, on role strain and depressive symptoms of
      adult-child family caregivers of older people with dementia. BACKGROUND: Family
      caregivers also employed for pay are known to be affected by work demands, i.e.
      excessive workload and time pressures. However, few studies have shown how these
      work demands and reconciliation between work and family caregiving influence
      caregivers' role strain and depressive symptoms. METHOD: For this cross-sectional
      study, secondary data were analysed for 119 adult-child family caregivers of
      older people with dementia in Taiwan using hierarchical multiple regression.
      RESULTS: After adjusting for demographic characteristics, resources and role
      demands overload, family caregivers with full-time jobs (beta=0.25, P<0.01) and
      more difficulty reconciling work and caregiving roles (beta=0.36, P<0.01)
      reported significantly more role strain than family caregivers working part-time
      or unemployed. Family caregivers with more work inflexibility reported more
      depressive symptoms (beta=0.29, P<0.05). CONCLUSION: Work demands affected family
      caregivers' role strain and depressive symptoms. Working full-time and having
      more difficulty reconciling work and caregiving roles predicted role strain; work
      inflexibility predicted depressive symptoms. These results can help clinicians
      identify high-risk groups for role strain and depression. Nurses need to assess
      family caregivers for work flexibility when screening for high-risk groups and
      encourage them to reconcile working with family-care responsibilities to reduce
      role strain.

PMID- 21077934
TI  - Transformational leadership training programme for charge nurses.
AB  - AIM: This paper is a report of an evaluation of the effects of a transformational
      leadership training programme on Unit Charge Nurses' leadership practices.
      BACKGROUND: Current healthcare regulations in the European Union and
      accreditation efforts of hospitals for their services mandate transformation in
      healthcare services in Turkey. Therefore, the transformational leadership role of
      nurse managers is vital in determining and achieving long-term goals in this
      process. METHOD: The sample consisted of 30 Unit Charge Nurses with a
      baccalaureate degree and 151 observers at two university hospitals in Turkey.
      Data were collected using the Leadership Practices Inventory-Self and Observer
      (applied four times during a 14-month study process from December 2005 to January
      2007). The transformational leadership training programme had theoretical (14
      hours) and individual study (14 hours) in five sections. Means, standard
      deviations and percentages, repeated measure tests and two-way factor analysis
      were used for analysis. RESULTS: According the Leadership Practices Inventory
      Self and Observer ratings, leadership practices increased statistically
      significantly with the implementation of the programme. There were no significant
      differences between groups in age, length of time in current job and current
      position. The Unit Charge Nurses Leadership Practices Inventory self-ratings were
      significantly higher than those of the observers. CONCLUSION: There is a need to
      develop similar programmes to improve the leadership skills of Unit Charge
      Nurses, and to make it mandatory for nurses assigned to positions of Unit Charge
      Nurse to attend this kind of leadership programme.

PMID- 21077935
TI  - Obesity interventions for people with a learning disability: an integrative
      literature review.
AB  - AIM: This paper is a review of the effectiveness of non-surgical, non
      pharmaceutical interventions designed to promote weight loss in people with a
      learning disability and how qualitative evidence on people's experiences and
      motivations can help understanding of the quantitative research outcomes.
      BACKGROUND: The health risks of obesity underline the importance of effective
      evidence-based weight loss interventions for people with learning disabilities as
      they are at increased risk of being overweight. DATA SOURCES: Papers published
      from 1998 to 2009 were identified through searches of the Cumulative Index for
      Nursing and Allied Health Literature, Proquest, Medline (PubMed), PSYCHINFO
      databases, and the Cochrane Library. REVIEW METHODS: An integrative review method
      was used. Studies included were non-surgical or non-pharmaceutical interventions
      aimed at weight reduction for people with a learning disability. Synthesis of the
      findings related to study design, participants, types of interventions, outcome
      measures and participant perspectives. RESULTS: Twelve studies met the inclusion
      criteria. The most common research design was quasi-experimental pretest and post
      test. Few researchers used a clinical trial approach, and there was only one
      predominantly qualitative study. Interventions were mainly focused on energy
      intake, energy expenditure or health promotion. Only a few studies incorporated
      behaviour modification approaches. CONCLUSION: Nurses who work with clients with
      learning disabilities have a key role to play in the management of obesity.
      Future research needs to focus on qualitative studies of the perceptions of
      clients and their families, controlled trials investigating the effectiveness of
      interventions and their costs and sustainability, and longitudinal studies
      examining weight loss over time.

PMID- 21077936
TI  - Cervimycin C resistance in Bacillus subtilis is due to a promoter up-mutation and
      increased mRNA stability of the constitutive ABC-transporter gene bmrA.
AB  - Two independent cervimycin C (CmC)-resistant clones of Bacillus subtilis were
      identified, each carrying two mutations in the intergenic region preceding the
      ABC transporter gene bmrA. In the double mutant, real-time PCR revealed an
      increased amount of bmrA mRNA with increased stability. Accordingly, isolation of
      membrane proteins yielded a strong band at 64 kDa corresponding to BmrA. Analyses
      showed that one mutation optimized the -35 box sequence conferring resistance to
      3 MUM CmC, while the +6 mutation alone had no effect, but increased the potential
      of the strain harboring the -35 mutation to grow at 5 MUM CmC. Transcriptional
      fusions revealed an elevated bmrA promoter activity for the double mutant.
      Electrophoretic mobility shift assays (EMSAs) confirmed a 30-fold higher binding
      affinity of RNA polymerase for this mutant compared with the wild type, and the
      effect was due to the -35 box alteration of the bmrA promoter. In vitro
      transcription experiments substantiated the results of the EMSA. EMSAs in the
      presence of heparin indicated that the mutations did not influence the formation
      and/or the stability of open complexes. Half-life measurements demonstrated that
      the +6 mutation stabilized bmrA mRNA ~ 2-fold. Overall, we found that an ABC
      transporter confers antibiotic resistance by the cumulative effects of two
      mutations in the promoter region.

PMID- 21077937
TI  - Evidence of clonazepam abuse liability: results of the tools developed by the
      French Centers for Evaluation and Information on Pharmacodependence (CEIP)
      network.
AB  - Recent observations suggest the existence of clonazepam abuse. To determine its
      importance in France, a quantitative and systematic synthesis of all clonazepam
      data of several epidemiological tools of the Centers for Evaluation and
      Information on Pharmacodependence (CEIP) network has been performed in comparison
      with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have
      been analysed from different epidemiological tools: OSIAP survey that identifies
      drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs
      and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities
      of use and data from regional French health reimbursement system. In OSIAP
      survey, the proportion of clonazepam falsified prescriptions among all BZD
      falsified prescriptions increased. During the 2006 OPPIDUM survey, the analysis
      of the BZD modalities of use highlights clonazepam abuse liability (for example
      23% of illegal acquisition), in second rank after flunitrazepam. Studies based on
      data from the French health reimbursed system show that 1.5% of subjects with
      clonazepam dispensing had a deviant behaviour. Among BZD, clonazepam has the
      second most important doctor-shopping indicator (3%) after flunitrazepam. All
      these data provide some arguments in favour of clonazepam abuse liability in real
      life and the necessity to reinforce its monitoring.

PMID- 21077938
TI  - An improved model to investigate the efficacy of antidyskinetic agents in
      hemiparkinsonian rats.
AB  - A number of experimental models of L-DOPA-induced dyskinesia have been proposed,
      but these models result in a low to medium rate of dyskinetic animals with mild
      to severe symptoms. The objective of this study was to combine a model of 6-OHDA
      induced parkinsonism and of L-DOPA-induced dyskinesia in rats to establish a
      reliable preclinical model. Two stereotaxic injections of 6-OHDA were
      administered in the left striatum. This model led to 90-100% of rats with a
      marked contralateral circling behaviour, significant limb use asymmetry (20%), a
      decrease in ipsilateral striatal dopamine content (70%) and degeneration of
      dopamine neurons in the substantia nigra (70%). Chronic treatment with L-DOPA was
      administered for 35 days and consisted of three phases with incremental daily
      doses. The third phase resulted in 83-90% of rats developing severe abnormal
      involuntary movements (AIMs) which included limb and locomotive dyskinesia, axial
      dystonia and orolingual dyskinesia. Reproducibility of the model, criteria of
      strict blinding, placebo-controlled design, randomization of study subjects and
      pretrial determination of sample size were used to measure efficacy of amantadine
      and istradefylline and to validate the protocol design. Acute or subchronic post
      treatment with amantadine reduced the severity of dyskinesia while istradefylline
      punctually attenuated AIMs. Our experimental conditions using gradual development
      of dyskinesia induced by increasing doses of L-DOPA resulted in a reliable model
      of L-DOPA-induced dyskinesia with a high rate of dyskinetic rats.

PMID- 21077939
TI  - Caffeic acid phenethyl ester protects against oxidative stress-related renal
      dysfunction in rats treated with cyclosporin A.
AB  - The therapeutic index of cyclosporin A (CsA), an immunosuppressive drug, is
      limited by its nephrotoxic effect. Oxidative stress is suggested to play a
      crucial role as pathogenic factors. The present study aimed at investigating the
      effects of caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, on renal
      function, morphology, and oxidative stress following CsA treatment. Rats were
      treated with vehicle, CsA (50 mg/kg), and CsA plus CAPE (10 and 30 MUmol/kg) for
      10 days. Renal function, histopathology, and tissue malondialdehyde (MDA) and
      reduced glutathione (GSH) levels were evaluated 24 h after the last treatment.
      CsA produced nephrotoxicity as indicated by a significant increase in serum
      creatinine and blood urea nitrogen, but decrease creatinine and urea clearance
      compared to those treated with vehicle. Severe vacuolations and tubular necrosis
      were evident in the kidney of CsA-treated rats. CsA also increased renal MDA and
      decreased GSH content significantly. Administration of CAPE along with CsA
      restored all the changes caused by CsA. These results clearly demonstrate the
      pivotal role of oxidative stress and its relation to renal dysfunction and also
      point to the protective potential of CAPE against CsA nephrotoxicity. The
      protection afforded by CAPE is mediated, at least in part, through inhibiting
      renal lipid peroxidation and enhancing or maintaining the antioxidant glutathione
      content.

PMID- 21077940
TI  - Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive
      oxygen species.
AB  - Oxidized low density lipoprotein (ox-LDL) and lectin-like oxidized low density
      lipoprotein receptor-1 (LOX-1) have been implicated in the development of
      atherosclerosis. This study was designed to investigate the expression regulation
      of LOX-1 by ox-LDL and the potential underlying mechanisms in cultured rat
      vascular smooth muscle cells (VSMCs). VSMCs were treated with ox-LDL, and the
      expressions of LOX-1 mRNA and proteins were determined by RT-PCR and western
      blotting, respectively. The intracellular reactive oxygen species (ROS)
      production was monitored by flow cytometry with fluorescence probe, DCFH(2) -DA.
      The effect of several inhibitors including aspirin, NDGA, allopurinol, apocynin,
      and rotenone on ox-LDL-induced ROS formation and LOX-1 expression was also
      investigated. The roles of NF-kappaB p65 and JNK were explored. Ox-LDL
      significantly induced LOX-1 expression at both mRNA and protein levels in a dose
      dependent and time-dependent manner. Aspirin, NDGA, and preconditioned apocynin
      suppressed ox-LDL-induced intracellular ROS production and LOX-1 expression,
      while allopurinol and rotenone failed to do so. Vitamin C and N-acetyl-l-cysteine
      demonstrated similar effect. Furthermore, both NF-kappaB p65 expression and
      phosphorylated JNK (p-JNK) to JNK expression ratio were elevated after ox-LDL
      treatment. In addition, the NF-kappaB inhibitor PDTC and JNK inhibitor SP600125
      pretreatment partly abolished ox-LDL-induced LOX-1 expression. These findings
      suggested that ROS mediated ox-LDL-induced LOX-1 expression in VSMCs through NF
      kappaB and JNK signaling pathways.

PMID- 21077941
TI  - Effects of florfenicol on LPS-induced nitric oxide and prostaglandin E2
      production in RAW 264.7 macrophages.
AB  - Florfenicol, an antibiotic commonly used to treat infections, has previously been
      shown to modulate lipopolysaccharide (LPS)-induced early cytokine responses by
      blocking the nuclear factor-kappaB (NF-kappaB) pathway. In this study, we
      investigated the effects of florfenicol on nitric oxide (NO) and prostaglandin E2
      (PGE2) production as well as on inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) expression in LPS-stimulated murine RAW 264.7
      macrophages. We also analysed the effects of florfenicol on mitogen-activated
      protein kinase (MAPK) pathways. Florfenicol significantly inhibited LPS-induced
      NO and PGE2 production. Consistent with these observations, mRNA and protein
      expression of iNOS and COX-2 were also inhibited by florfenicol in a dose
      dependent manner. Furthermore, phosphorylation of p38 and extracellular signal
      regulated kinase 1/2 (ERK1/2) in LPS-stimulated RAW 264.7 cells was suppressed by
      florfenicol. However, c-Jun N-terminal kinase (JNK) phosphorylation remained
      unaffected. Using specific inhibitors of ERK and p38, we found that florfenicol
      may inhibit NO and PGE2 mostly through ERK and p38 pathway. These results suggest
      that florfenicol inhibits NO and PGE2 production in conjunction with an
      inhibition of iNOS and COX-2 expression, at least partially via suppression of
      ERK1/2 and p38 MAPK phosphorylation.

PMID- 21077942
TI  - Hepatic and renal toxicities of indomethacin acid, salt form and complexed forms
      with hydroxypropyl-beta-cyclodextrin on Wistar rats after oral administration.
AB  - Indomethacin (IM), a non-steroidal anti-inflammatory drug, has the capacity to
      induce hepatic and renal injuries when administrated systemically. The aim of
      this study is to assess the IM absorption from complexed forms when orally
      administered to rats, by means of a comparative evaluation of its capacity to
      induce hepatic and renal injury in different forms, namely IM acid, IM sodium
      salt or IM complexed with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), using
      freeze- and spray-drying methods. A total of 135 Wistar rats weighing 224.4 +/-
      62.5 g were put into 10 groups. They were allowed free access to water but were
      maintained on fast for 18 h before the first administration until the end of the
      experiment. Water and HP-beta-CD (control groups) and IM acid form, IM
      trihydrated-sodium-salt and IM-HP-beta-CD spray- and freeze-dried, at normal and
      toxic doses (test groups), were orally administered once/day for 3 days. Seventy
      two hours after the first administration, the animals were sacrificed and a
      fragment of the liver and one kidney were collected and prepared for
      histopathological evaluation. Lesion indexes (rated 0/4 for liver and 0/3 for
      kidney) were developed and the type of injury scored according to the severity of
      damage. A statistical analysis of the severity and incidence of lesions was
      carried out. Animals administered with IM complexed forms showed similar hepatic
      and renal lesions, both in toxic and therapeutic doses, when compared with those
      observed in animals administered with IM acid or salt forms. This suggests that
      under the present experimental conditions, IM is equally absorbed from the
      gastrointestinal tract, independently of the administered IM form.

PMID- 21077944
TI  - Oral antiplatelet agents in ACS: from pharmacology to clinical differences.
AB  - Antiplatelet agents play an essential role in the treatment of acute coronary
      syndrome (ACS). Numerous clinical trials have established the value of
      antiplatelet therapies for ACS. Aspirin (ASA), thienopyridines and GP IIb/IIIa
      antagonists comprise the major classes of antiplatelet therapies demonstrated to
      be of benefit in the treatment of ACS. Thienopyridines are a class of drugs that
      function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet
      receptors. Currently, clopidogrel, a second generation thienopyridine, is the
      main drug of choice and the combination of aspirin and clopidogrel is
      administered orally for the treatment of ACS. Recently, a third generation of
      thienopyridines has been introduced represented by prasugrel that has
      demonstrated promising results in ACS patients treated with percutaneous coronary
      intervention (PCI). A number of nonthienopyridine oral antiplatelet drugs are
      under development, and one of them, ticagrelor has already been tested in a major
      phase III clinical trial, PLATO, with the inclusion of a broad spectrum of
      patients with ACS. The present review aims to discuss the present knowledge about
      the safety and efficacy of oral antiplatelet treatment of patients with ACS.

PMID- 21077943
TI  - Comparison between orlistat plus l-carnitine and orlistat alone on inflammation
      parameters in obese diabetic patients.
AB  - To evaluate the effects of 1-year treatment with orlistat plus L-carnitine
      compared to orlistat alone on body weight, glycemic and lipid control, and
      inflammatory parameters in obese type 2 diabetic patients. Two hundred and fifty
      eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated
      hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents
      or insulin were enrolled in this study and randomized to take orlistat 120 mg
      three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three
      times a day. We evaluated the following parameters at baseline and after 3, 6, 9,
      and 12 months: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)
      ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting
      plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA
      IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), triglycerides (Tg), adiponectin (ADN),
      leptin, tumor necrosis factor-alpha (TNF-alpha), vaspin, and high-sensitivity C
      reactive protein (Hs-CRP). We observed a better decrease in body weight, glycemic
      profile, HOMA-IR, LDL-C, and ADN and a faster improvement in FPI, TC, Tg, leptin,
      TNF-alpha, Hs-CRP with orlistat plus L-carnitine compared to orlistat alone. We
      also recorded an improvement in vaspin with orlistat plus l-carnitine not reached
      with orlistat alone. Orlistat plus L-carnitine gave a better improvement in body
      weight, glycemic and lipid profile compared to orlistat alone; furthermore, a
      faster and better improvement in inflammatory parameters was observed with
      orlistat plus L-carnitine compared to orlistat alone.

PMID- 21077945
TI  - Cardiovascular effects of 1-nitro-2-phenylethane, the main constituent of the
      essential oil of Aniba canelilla, in spontaneously hypertensive rats.
AB  - This study investigated the cardiovascular responses to the essential oil of
      Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in
      spontaneously hypertensive rats (SHRs). In anesthetized SHRs, intravenous (i.v.)
      bolus injections of EOAC (1-20 mg/kg) or NP (1-10 mg/kg) elicited dose-dependent
      hypotensive and bradycardiac effects, which were characterized in two periods
      (phases 1 and 2). The first rapid component (phase 1) evoked by EOAC and NP both
      at 10 mg/kg was absent after left ventricle injection, fully abolished by
      bilateral vagotomy and perineural treatment of both cervical vagus nerves with
      capsaicin (250 MUg/mL) while remained unaltered by i.v. pretreatment with
      capsazepine (1 mg/kg) or ondansetron (30 MUg/kg). In conscious SHRs, NP (5 and 10
      mg/kg, i.v.) evoked rapid hypotensive and bradycardiac effects (phase 1) that
      were fully abolished by methylatropine (1 mg/kg, i.v.) pretreatment. In rat
      endothelium-containing mesenteric preparations, increasing concentrations (0.1
      1000 MUg/mL) of EOAC and NP relaxed the phenylephrine-induced contraction in a
      concentration-dependent manner. It is concluded that NP induces a vago-vagal
      bradycardiac and depressor reflex (phase 1) that apparently results from the
      stimulation of vagal pulmonary rather than cardiac C-fiber afferents. This effect
      does not appear to involve activation of either vanilloid TPRV(1) or 5-HT(3)
      receptors located on vagal sensory nerves. The phase 2 hypotensive response to
      i.v. NP seems to result, at least in part, from its direct vasodilatory effect on
      the peripheral smooth muscle. All in vivo and in vitro effects of EOAC are mostly
      attributed to the actions of its main constituent NP.

PMID- 21077947
TI  - The correlation between NF-kappaB inhibition and disease activity by
      coadministration of silibinin and ursodeoxycholic acid in experimental colitis.
AB  - NF-kappaB is one of the most important nuclear factors responsible for
      overexpression of proinflammatory cytokines. This is demonstrated by increased NF
      kappaB activity and other dependent immune factors in inflammatory bowel disease
      (IBD). Anti-inflammatory effects of silibinin and ursodeoxycholic acid (UDCA)
      along with their NF-kappaB inhibitory property are thought to be beneficial in
      colitis. Trinitrobenzene sulfonic acid was used to induce colitis rat models.
      After instillation, 48 rats were treated with oral silibinin, UDCA alone or a
      combination of both. Intraperitoneal dexamethasone was used in the control group.
      After 12 days of treatment, colonic samples were tested for the severity of
      mucosal damage macroscopically and microscopically. The levels of activated NF
      kappaB, IL-1beta, TNF-alpha, myeloperoxidase, thiobarbituric acid reactive
      substances (TBARS), protein carbonyl, and the antioxidant power of the bowel
      homogenates were determined. The results indicated a significant reduction in NF
      kappaB activity as well as the levels of IL-1beta, TNF-alpha, TBARS, protein
      carbonyl, myeloperoxidase activity, and an improvement in antioxidant power of
      colitis in treated rats. Combination therapy resulted in a more prominent
      improvement in bowel antioxidant power and myeloperoxidase activity. In
      conclusion, combination of silibinin and UDCA by inhibition of NF-kappaB and
      other relevant inflammatory factors of colitis is a good candidate for management
      of Crohn's disease.

PMID- 21077946
TI  - Antispasmodic effects of eugenol on rat airway smooth muscle.
AB  - This study was undertaken to assess the effects of eugenol (EUG) on tracheal
      muscle (TM) and the putative mechanisms underlying these effects. Cumulatively
      increasing concentrations (1-1000 MUm) of EUG did not affect the resting tonus of
      TM. However, EUG (1-2000 MUm) reduced the contractions induced by electrical
      field stimulation (IC(50) = 842.3 +/- 52.7 MUm), an effect that was unaltered by
      either 10 MUm montelukast (IC(50) = 816.1 +/- 70.1 MUm) or 2 MUm indomethacin
      (IC(50) = 693.1 +/- 170.8 MUm). EUG also completely relaxed the sustained
      contractile responses to 80 mM K(+) (IC(50)  = 597.3 +/- 60.6 MUm) and 1 MUm
      carbamoylcholine (IC(50) = 571.3 +/- 148.8 MUm), an effect that was unaltered by
      indomethacin (2 MUm). Under Ca(2+) -free conditions, EUG reduced the ACh-induced
      contractions (IC(50) = 703.4 +/- 256.1 MUm), the CaCl2 -induced contractions in
      preparations pretreated with 60 MUm ACh in the presence of nifedipine, and the
      Ba(2+) -induced contractions in preparations depolarized with K(+) . In tracheal
      preparations maintained in Ca(2+) -containing solution, EUG (300-2000 MUm)
      relaxed the contractile response to phorbol dibutyrate (1 MUm), an activator of
      protein kinase C. It is concluded that in TM, EUG induces a myogenic
      antispasmodic effect (not modulated by arachidonic acid derivatives) either
      through various mechanisms almost with the same pharmacological potency or via an
      action on a step common to all of them. These mechanisms seem to include blockade
      of voltage- and receptor-operated Ca(2+) channels, IP3 -induced Ca(2+) release
      from sarcoplasmic reticulum and reduction of the sensitivity of contractile
      proteins to Ca(2+) .

PMID- 21077948
TI  - Cyclooxygenase-independent mechanism of ibuprofen-induced antipyresis: the role
      of central vasopressin V1 receptors.
AB  - This study compared the antipyretic effects of ibuprofen and indomethacin
      regarding the efficacy in blocking fevers induced by lipopolysaccharide (LPS from
      E. coli) or pyrogenic mediators that act on prostaglandin (PG)-dependent and PG
      independent pathways. The content of PGE2 in the cerebrospinal fluid (CSF) and
      the dependence on central arginine vasopressin (AVP) release by both antipyretics
      were also compared during the reduction of LPS-induced fever. Finally, we
      investigated the effect of ibuprofen on hypothalamic cytokine content during LPS
      induced fever. Ibuprofen (intraperitoneally, i.p.) dose-dependently inhibited the
      fever induced by LPS (intravenously, i.v.). Indomethacin (2 mg/kg) and ibuprofen
      (10 mg/kg) reduced the fever induced by i.c.v. injection of interleukin (IL)
      1beta, IL-6, tumor necrosis factor (TNF)-alpha, or arachidonic acid (AA).
      Ibuprofen, but not indomethacin, inhibited i.c.v. endothelin-1- and pre-formed
      pyrogenic factor (PFPF)-induced fever. Neither ibuprofen nor indomethacin
      affected fever by PGE2 , PGF(2alpha) , or corticotrophin-releasing factor (CRF);
      however, both reduced the CSF PGE2 content after LPS. Bilateral injection of the
      AVP V(1) receptor antagonist d(CH2)5 Tyr(Me)AVP into the ventral septal area
      blocked both ibuprofen- and indomethacin-induced antipyresis. Ibuprofen did not
      modify the hypothalamic increase in either IL-1beta or IL-6 induced by LPS. In
      conclusion, although the antipyretic effect of ibuprofen involves the blockage of
      central production of PGE2 and the endogenous release of AVP, differently from
      low dose of indomethacin, ibuprofen not only reduced the fever induced by PGE2 
      dependent, but also, that induced by PGE2 -independent endogenous pyrogens.
      Moreover, ibuprofen does not affect the hypothalamic synthesis/release of IL
      1beta and IL-6.

PMID- 21077949
TI  - Post-transplant lymphoproliferative disorders in lung transplant recipients: 20
      yr experience at the University of Minnesota.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal
      complications of solid organ transplantation. The natural history of PTLD varies
      considerably among the different types of organs transplanted. While lung
      transplant recipients are highly susceptible to PTLD, there are only a few small
      studies that detail PTLD in this setting. We undertook this study to better
      describe the characteristics and treatment response in PTLD after lung
      transplantation. We conducted a retrospective chart review of lung and heart/lung
      transplant recipients between 1985 and 2008. A total of 32 cases (5%) of PTLD
      were identified in 639 patients. The median interval after transplantation to the
      diagnosis was 40 (3-242) months. Eight patients (25%) were diagnosed within one
      yr of transplantation and had PTLD predominantly within the thorax and allograft.
      Twenty-four patients (75%) were diagnosed more than one yr after transplantation
      and their tumors mainly affected the gastrointestinal tract. Monomorphic PTLD,
      diffuse large B-cell lymphoma, was diagnosed in 91%. Treatment of PTLD varied
      according to stage and clinical circumstances. Twenty-four patients (75%) have
      died. The median overall survival was 10 (0-108) months. PTLD after lung
      transplantation remains a challenge as a result of its frequency, complexity and
      disappointing outcome.

PMID- 21077950
TI  - Clinical outcomes of liver transplantation for HBV-related hepatocellular
      carcinoma: data from the NIH HBV OLT study.
AB  - BACKGROUND: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is an
      indication for orthotopic liver transplantation (OLT) in patients with tumor
      stage within the United Network for Organ Sharing criteria. The number of
      patients listed for HBV-related HCC is increasing, while the number of patients
      listed for HBV-related cirrhosis is declining presumptively because of the
      availability of more effective oral nucleos(t)ide analogues. This study presents
      the final, long-term outcome of patients transplanted for HBV-related HCC in the
      National Institutes of Health (NIH) HBV OLT Study Group. RESULTS: Ninety-eight
      patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV-related HCC.
      With a mean follow-up of 36.5 months post-OLT, 12 (12.2%) patients developed
      recurrence of HCC. Multivariate analysis did not find a statistically significant
      role of gender, tumor stage at OLT, pre-OLT HCC treatment, recurrence of HBV, or
      duration of HCC diagnosis pre-OLT in predicting HCC recurrence. Serum alpha
      fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically
      significant in predicting HCC recurrence (p=0.003). HCC recurrence was
      significantly associated with decreased post-OLT survival. CONCLUSION: HCC is the
      most common indication for OLT in patients with chronic hepatitis B in the era of
      more effective oral antivirals. Serum AFP at the time of OLT is significantly
      associated with HCC recurrence.

PMID- 21077951
TI  - Hyponatremia a valuable predictor of early mortality in patients with cirrhosis
      listed for liver transplantation.
AB  - The current policy for organ allocation in liver transplantation is to give
      priority to the sickest patients mostly using model for end-stage liver disease
      (MELD) score in ranking. However, other factors as serum sodium may be of value
      in predicting early mortality. In this single-center study, patients with
      cirrhosis over age 14 on the liver transplant wait-list from September 1998 to
      June 2007 were followed for six months from the time of listing to evaluate the
      value of hyponatremia on mortality. Of 612 listed patients, 51 were transplanted
      who were excluded from survival analysis and 55 died without transplantation
      within the first three months. The numbers of transplanted and dead patients
      during months 3-6 were 29 and 24, respectively. Both MELD score and serum sodium
      at the time of listing were independent predictors of early mortality. On
      bivariate analysis, serum sodium of <130 mEq/L beside MELD was a significant
      predictor of mortality within 90 and 180 d. Serum sodium level <135 mEq/L masked
      the difference in mortality between patients with refractory and non-refractory
      ascites. Serum sodium level of <130 mEq/L and an increased MELD score are
      significant predictors of early mortality in patients listed for liver
      transplantation.

PMID- 21077952
TI  - Albuminuria after renal transplantation: maintenance with sirolimus/low-dose
      tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.
AB  - Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has
      been associated with proteinuria. We report long-term outcomes of kidney
      transplant recipients maintained on steroid-free regimens, either SRL with low
      dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose
      tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients
      receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All
      patients were induced with rabbit antithymocyte globulin followed by early
      steroid withdrawal. Comparisons were made of patient and graft survival, graft
      function, acute rejection, and albuminuria. There were no significant differences
      between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival,
      occurrence of acute rejection, or graft function. There was no difference in the
      proportion of patients with albumin/creatinine ratio (ACR) >=300 MUg/mg (19% vs.
      20%), but more patients in the SRL group were receiving renin-angiotensin system
      blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with
      histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of
      albuminuria. Long-term outcomes are similar at our center for kidney transplant
      patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of
      albuminuria was not different, significantly more SRL-treated patients were
      receiving antiproteinuric medications.

PMID- 21077954
TI  - Import kidney offers and DonorNet: a view from the trenches.
AB  - The ability of DonorNet2007((r)) screening functions to expedite placement of
      locally rejected kidneys is unknown. We separately evaluated non-mandatory share
      regional (n = 641) and national (n = 720) kidney offers to our center between
      5/2007 and 2/2009 for cold ischemia time at offer (oCIT) with respect to
      candidate ranking to identify donor factors associated with early oCIT and assess
      the impact of screening functions. oCIT was <7 h after recovery in 83.2% of
      regional and 34% of national offers. Of national offers, donor characteristics
      significantly (p < 0.05) associated with oCIT less than median (10 h) were as
      follows: age <4 yr (vs. 4-35 yr), age >69 yr (vs. 60-69 yr), serum creatinine
      peak >2.0 and terminal >2.0 mg/dL, and glomerulosclerosis >15% (vs. 0-5%). The
      trend in early offers was predominantly attributed to greater proportions of pre
      recovery offers. Only one factor, age >69 yr, was significantly associated with
      proportionately more offers at low sequence numbers. Our data suggest an effect
      of age within DonorNet((r)) screening functions to reduce candidate list size and
      result in earlier offers. Shorter offer oCITs are otherwise occur largely because
      of pre-recovery offers from donors with certain types of pre-recovery
      characteristics.

PMID- 21077953
TI  - Patients' level of knowledge measured five days after kidney transplantation.
AB  - BACKGROUND: Kidney recipients' knowledge is important in terms of coping with
      short-term problems posed by transplantation and the long-term outcome. Little
      attention has been given to the development of instruments for measuring
      patient's knowledge in this field. AIM: The purpose of this study was to describe
      the development of a knowledge questionnaire for kidney recipients and to explore
      possible factors related to the knowledge level. METHODS: The sample consisted of
      159 kidney recipients at a Norwegian transplant center, answering the
      questionnaire five d post-transplantation. RESULTS: The questionnaire was
      generated on the basis of literature review and clinical experience - and was
      pilot tested. Mean score of the questionnaire was 11, of 19 obtainable points.
      Longer duration of kidney disease was significantly correlated with an increased
      knowledge level, whereas the longer the time on dialysis prior to transplantation
      and post-operative complications were found to have significantly negative impact
      on total knowledge score. CONCLUSIONS: The positive impact of disease duration
      may suggest that insight gained over time makes patients better prepared for the
      transplantation itself and for life post-transplant. However, the negative impact
      of dialysis duration could be attributed to impaired cognitive function imposed
      by chronic dialysis treatment. Further research is needed regarding the
      questionnaire's responsiveness to educational interventions.

PMID- 21077955
TI  - Clinical features of late onset non-infectious pulmonary complications following
      pediatric allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Late onset non-infectious pulmonary complications (LONIPCs) are major
      causes of morbidity and mortality after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). We evaluated the incidence and the outcomes of
      LONIPCs in children who underwent allo-HSCT. METHODS: Data for 143 children who
      underwent allo-HSCT at Asan Medical Center between April 2002 and April 2009 were
      reviewed, and the 127 who survived more than three months were enrolled. RESULTS:
      Eleven (8.7%) developed LONIPCs at a median eight months (range 3-14 months)
      after allo-HSCT, presenting with cough and dyspnea. Six had bronchiolitis
      obliterans and five had idiopathic pneumonia syndrome. FVC declined more
      significantly in LONIPC than in non-LONIPC patients three months after HSCT. A
      significant risk factor for the development of LONIPCs was chronic graft-versus
      host disease (GVHD) (p = 0.002). At a median follow-up of 36 months, the three-yr
      overall survival rate in LONIPC patients was significantly lower than that of non
      LONIPC patients (37.4% vs. 72.7%, p = 0.02). The major cause of death was
      respiratory failure. CONCLUSIONS: Along with chronic GVHD, deterioration of
      pulmonary function at three months after HSCT may help in the early
      identification of patients at risk of subsequent LONIPCs. Considering the poor
      prognosis of LONIPC, strategies should be aimed at their prevention.

PMID- 21077956
TI  - Taking immunosuppressive medications effectively (TIMELink): a pilot randomized
      controlled trial in adult kidney transplant recipients.
AB  - BACKGROUND: Immunosuppressive medication non-adherence is one of the most
      prevalent but preventable causes of poor outcomes in adult renal transplant
      recipients, yet there is a paucity of studies testing interventions in this area.
      METHODS: Using a randomized controlled trial design, 30 adult renal transplant
      recipients were screened for medication non-adherence using electronic
      monitoring. Fifteen non-adherent participants were randomized to receive either a
      continuous self-improvement intervention or attention control management. The six
      month continuous self-improvement intervention involved the participant and
      clinical nurse specialist collaboratively identifying the person's life routines,
      important people, and possible solutions to enhance medication taking. The
      participant then received individual monthly medication taking feedback delivered
      via a graphic printout of daily medication taking generated from electronic
      monitoring. RESULTS: The mean medication adherence score for the continuous self
      improvement intervention group (n = 8) was statistically significantly higher
      than the attention control group's (n = 5) mean medication adherence score (p =
      0.03). The continuous self-improvement intervention effect size (Cohen's d) was
      large at 1.4. Participants' perceptions of the intervention were highly
      favorable. CONCLUSIONS: The continuous self-improvement intervention shows
      promise as an effective and feasible approach to improve medication adherence in
      adult renal transplant recipients. A fully-powered study with a diverse sample is
      needed to confirm these preliminary findings.

PMID- 21077957
TI  - Kidney transplant performed after liver transplant: a single center experience.
AB  - Changes in liver allocation due to institution of the model for end-stage liver
      disease/PELD criteria have led to an increase in the number of patients receiving
      liver transplants who have elevated creatinine. Whether these patients' renal
      dysfunction is reversible or not and whether they should receive combined liver
      and kidney transplants (KTXs) are individualized decisions, although some
      criteria are becoming clearer. A part of this decision must consider the outcomes
      of patients who have liver transplants alone but later require KTXs. We herein
      describe our single-center experience with this patient population. Our data show
      that KTX subsequent to liver transplantation (TX) is generally safe and
      effective, with a possibly higher surgical complication rate than standard KTX.
      Outcomes analysis showed not statistically different patient survival of KTXs
      performed after liver transplant (KALT) compared with KTX alone. Death censored
      graft survival was statistically lower in the KALT group but this largely accrued
      in the first three yr after transplant and was nearly equivalent by 10 yr.

PMID- 21077958
TI  - Long-term outcome in 42 pediatric liver transplant patients with alpha 1
      antitrypsin deficiency: a single-center experience.
AB  - INTRODUCTION: We examined the long-term outcome of transplantation for alpha 1
      antitrypsin deficiency (A1ATD). METHOD: Data were reviewed on 42 transplants in
      35 children with A1ATD over 42 yr and compared with 129 transplants in 116
      children with biliary atresia (BA). RESULTS: Over 50% of patients were followed
      up for >10 yr. A1ATD were older than BA at transplantation, median age, 6.0 vs.
      1.0 yr (p < 0.0001), and transplanted earlier in the course of liver failure
      (total bilirubin, 2.7 mg/dL [1.4-6.9] vs. 9.7 mg/dL [2.9-15.4], p = 0.005).
      Patient survival was greater in A1ATD than BA: one-yr post-transplant, 82.7% vs.
      67.9%; five yr, 76.5% vs. 60.2%; and 10 yr, 76.5% vs. 55.9% (p = 0.03). Death
      censored graft survival was similar: one-yr post-transplant, 68.4% vs. 66.2%;
      five yr, 68.4% vs. 55.8%; and 10 yr, 68.4% vs. 52.5% (p = 0.2). Deaths were from
      infection, hemorrhage, and graft failure <6 months post-transplant. Patient
      survival improved at five yr from 33.3% pre-cyclosporine (CSA) (1969-1984) (n =
      6) to 76.5% in the CSA era (1985-1994) (n = 17) and 100% with tacrolimus (1995
      2006) (n = 12) (p = 0.007). CONCLUSIONS: The age at transplantation and the
      degree of liver dysfunction were related to the differences in graft and patient
      survival between A1AT and BA.

PMID- 21077959
TI  - High white blood cell count at diagnosis of childhood acute lymphoblastic
      leukaemia: biological background and prognostic impact. Results from the NOPHO
      ALL-92 and ALL-2000 studies.
AB  - Prognostic impact of peripheral blood white blood cell count (WBC) at the
      diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a
      population-based consecutive series of 2666 children aged 1-15 treated for ALL
      between 1992 and 2008 in the five Nordic countries (Denmark, Finland, Iceland,
      Norway and Sweden). Ten-year event-free (pEFS(10 y)) survival and overall (pOS(10
      y)) survival were 0.75 +/- 0.01 and 0.85 +/- 0.01, respectively. Although
      treatment intensity was determined by WBC, non-remission and relapsed patients
      still had significantly higher WBC than those in remission for B-cell precursor
      (BCP) (median WBC: 24.8 vs. 14.0 vs. 8.3 * 10(9) /L, P < 0.001), but not for T
      lineage (T-ALL) (median WBC: 127.8 vs. 113.0 vs. 86.8 * 10(9) /L, P = 0.22). pEFS
      was inversely related to WBC for BCP (P < 0.001), but not for T-ALL. WBC was not
      associated with risk of event for BCP or T-ALL for patients with minimal residual
      disease at the end of induction (MRD(d29) ) <10(-3). In contrast, for MRD(d29) >=
      10(-3) and <5% leukaemic blasts in bone marrow at day 29, the pEFS(5 y) for WBC <
      100.0 (N = 152) vs. >= 100.0 (N = 19) was 0.76 vs. 0.50 (P = 0.001). That was the
      case both for BCP (pEFS(5 y) 0.76 vs. 0.58) and for T-ALL (pEFS(5 y) 0.71 vs.
      0.38). Whether the inferior EFS for the subset of patients with high WBC and slow
      initial response to treatment reflects rare or overlooked cytogenetic aberrations
      as well as the factors that determine WBC levels at diagnosis awaits exploration.

PMID- 21077960
TI  - Prognostic variables and nomograms for renal cell carcinoma.
AB  - The term renal cell carcinoma (RCC) is used to describe a heterogeneous group of
      tumors that vary histologically, genetically and molecularly. Extensive research
      has been conducted to identify characteristics that predict outcomes among
      patients with RCC. In addition to histological subtype these include tumor size,
      patient age, mode of presentation and various hematological indices, among
      others. Several groups have incorporated these clinical and pathological features
      into nomograms which help the clinician better define individual patient
      prognosis and direct the optimum therapeutic approach. In the present article we
      review these prognostic variables and nomograms for RCC.

PMID- 21077961
TI  - Nationwide survey to evaluate the prevalence of varicoceles in South Korean
      middle school boys: a population based study.
AB  - OBJECTIVE: We carried out a nationwide epidemiological study to evaluate the
      prevalence and effect of varicoceles on testicular volume in South Korean
      adolescents. We also investigated the correlation between varicoceles and body
      mass index (BMI). METHODS: In this prospective study, physical examinations were
      carried out to assess the presence and severity of varicoceles in middle school
      boys from six regions of South Korea. Testicular volume, height and weight of all
      boys were measured. The prevalence of varicoceles was assessed. The associations
      between age, testicular volume, BMI, and the presence and severity of varicoceles
      were examined. RESULTS: A total of 1938 boys with a mean age of 14.1 years (range
      13-16 years) were screened. A varicocele was found on the left side in 295
      (15.2%) boys and on the right side in 8 (0.4%) boys. Bilateral varicoceles were
      found in 17 (0.9%) individuals. Of the subjects with a left varicocele, 151
      (51.2%), 80 (27.1%) and 64 (25.1%) boys had a grade 1, 2 or 3 varicocele,
      respectively. The prevalence of varicoceles did not increase with age. The
      proportion of boys with testicular size discrepancies increased with the severity
      of the varicocele. After adjusting for age, BMI had a negative correlation with
      the presence of varicoceles. CONCLUSIONS: The prevalence of varicoceles in South
      Korean middle school boys is 16.5%. The presence of varicoceles seems to have a
      negative effect on testicular growth. BMI has a significant inverse relationship
      with the occurrence of varicoceles.

PMID- 21077962
TI  - Does performance of robot-assisted laparoscopic radical prostatectomy within 2
      weeks of prostate biopsy affect the outcome?
AB  - OBJECTIVE: The aim of this study was to determine whether robot-assisted
      laparoscopic radical prostatectomy (RALP) performed within either 2 or 4 weeks of
      prostate biopsy is associated with surgical difficulty or immediate postoperative
      outcome. METHODS: Of the 121 patients that underwent RALP at our institution, 104
      patients were prospectively included. Patients were sequentially divided into
      three groups: first patient in group A (interval from biopsy to RALP: 2 weeks),
      second patient in group B (2-4 weeks), third patient in group C (more than 4
      weeks), fourth patient in group A, and so on. The clinical, operative,
      pathological, and postoperative functional data were collected. RESULTS: Group A
      consisted of 31 patients, group B of 33, and group C of 40 patients. Median
      patient age and median follow up were 61.1 years and 14.1 months, respectively.
      In group A, mean estimated blood loss was significantly higher than the other two
      groups, even though there was no significant difference in the mean console time.
      Postoperative complications did not make any difference among the groups. In the
      multivariable analysis, the interval from biopsy to surgery did not affect
      operative times or surgical margins, or the immediate postoperative outcomes
      (e.g. recovery of erectile function, continence, and biochemical recurrence).
      CONCLUSION: A short interval for less than two weeks between the prostate biopsy
      and the RALP seems to be feasible and safe. Further studies with larger samples
      are needed to corroborate these findings.

PMID- 21077964
TI  - A time of change.

PMID- 21077965
TI  - Is the rising demand for animal protein fuelling climate change?

PMID- 21077963
TI  - Unexpected enlargement of clinically silent pituitary gonadotroph adenoma induced
      by goserelin acetate given as treatment for prostate cancer.

PMID- 21077966
TI  - Comparison between genomic predictions using daughter yield deviation and
      conventional estimated breeding value as response variables.
AB  - This study compared genomic predictions using conventional estimated breeding
      values (EBV) and daughter yield deviations (DYD) as response variables based on
      simulated data. Eight scenarios were simulated in regard to heritability (0.05
      and 0.30), number of daughters per sire (30, 100, and unequal numbers with an
      average of 100 per sire) and numbers of genotyped sires (all or half of sires
      were genotyped). The simulated genome had a length of 1200 cM with 15,000 equally
      spaced Single-nucleotide polymorphism (SNP) markers and 500 randomly distributed
      Quantitative trait locus (QTL). In the simulated scenarios, the EBV approach was
      as effective as or slightly better than the DYD approach at predicting breeding
      value, dependent on simulated scenarios and statistical models. Applying a
      Bayesian common prior model (the same prior distribution of marker effect
      variance) and a linear mixed model (GBLUP), the EBV and DYD approaches provided
      similar genomic estimated breeding value (GEBV) reliabilities, except for
      scenarios with unequal numbers of daughters and half of sires without genotype,
      for which the EBV approach was superior to the DYD approach (by 1.2 and 2.4%).
      Using a Bayesian mixture prior model (mixture prior distribution of marker effect
      variance), the EBV approach resulted in slightly higher reliabilities of GEBV
      than the DYD approach (by 0.3-3.6% with an average of 1.9%), and more obvious in
      scenarios with low heritability, small or unequal numbers of daughters, and half
      of sires without genotype. Moreover, the results showed that the correlation
      between GEBV and conventional parent average (PA) was lower (corresponding to a
      relatively larger gain by including PA) when using the DYD approach than when
      using the EBV approach. Consequently, the two approaches led to similar
      reliability of an index combining GEBV and PA in most scenarios. These results
      indicate that EBV can be used as an alternative response variable for genomic
      prediction.

PMID- 21077967
TI  - Random regression analyses using B-splines functions to model growth from birth
      to adult age in Canchim cattle.
AB  - The objective of this work was to estimate covariance functions using random
      regression models on B-splines functions of animal age, for weights from birth to
      adult age in Canchim cattle. Data comprised 49,011 records on 2435 females. The
      model of analysis included fixed effects of contemporary groups, age of dam as
      quadratic covariable and the population mean trend taken into account by a cubic
      regression on orthogonal polynomials of animal age. Residual variances were
      modelled through a step function with four classes. The direct and maternal
      additive genetic effects, and animal and maternal permanent environmental effects
      were included as random effects in the model. A total of seventeen analyses,
      considering linear, quadratic and cubic B-splines functions and up to seven
      knots, were carried out. B-spline functions of the same order were considered for
      all random effects. Random regression models on B-splines functions were compared
      to a random regression model on Legendre polynomials and with a multitrait model.
      Results from different models of analyses were compared using the REML form of
      the Akaike Information criterion and Schwarz' Bayesian Information criterion. In
      addition, the variance components and genetic parameters estimated for each
      random regression model were also used as criteria to choose the most adequate
      model to describe the covariance structure of the data. A model fitting quadratic
      B-splines, with four knots or three segments for direct additive genetic effect
      and animal permanent environmental effect and two knots for maternal additive
      genetic effect and maternal permanent environmental effect, was the most adequate
      to describe the covariance structure of the data. Random regression models using
      B-spline functions as base functions fitted the data better than Legendre
      polynomials, especially at mature ages, but higher number of parameters need to
      be estimated with B-splines functions.

PMID- 21077968
TI  - Genetic variation in litter size and kit survival of mink (Neovison vison).
AB  - The aims of this study are to estimate variance components of litter size and kit
      survival rate and estimate genetic correlations of litter size and kit survival
      rate with dam's juvenile body weight and pregnancy length. Variance components
      for litter size and kit survival were analysed using an AI-REML approach, based
      on data from 1940 litters of the black colour type mink from 1996 to 2001. The
      models included (i) additive genetic effect of dam; (ii) dam and sire genetic
      effects; (iii) additive genetic effect of dam in relation to litter size and dam
      and sire genetic effects in relation to survival rate; (iv) additive genetic
      effect of dam to estimate the correlations of litter size or kit survival with
      dam juvenile body weight and pregnancy length on yearling dams (1357 litters).
      The dam heritabilities were of litter size (0.02-0.08) and survival rate (0.05
      0.10). The permanent effects of dam were important for litter size (0.15-0.19)
      but not for survival rate. A positive dam genetic correlation between litter size
      and survival rate was found at 1 week postpartum (0.42), and a positive sire
      genetic correlation between number of weaned kits and survival rate at the age of
      6 month (0.72). Litter size and survival rate were genetically antagonistically
      related to dam's juvenile body weight (-0.34 to -0.53). These results indicate
      the following: (i) it is possible to improve litter size and kit survival by
      selection, (ii) effective improvement of kit survival rate in the suckling period
      requires selection for maternal effect on kit survival and kit's own capacity to
      survive and later in the growth period for kit's own ability to survive and (iii)
      antagonistic genetic correlation of dam juvenile body weight with litter size and
      survival rate should be taken into consideration in mink breeding programs.

PMID- 21077969
TI  - Behavioural and endocrinological changes in Syrian hamsters (Mesocricetus
      auratus) under domestication.
AB  - This study aimed to quantify differences in response to stress between two
      strains of Syrian hamsters to evaluate the consequences of domestication in this
      species by measuring behavioural traits in the open-field, adrenal gland masses
      (ADR), and faecal and blood corticosterone concentrations (CC). We studied a
      laboratory (lab)- and a wild-derived population (wild). The lab hamsters were
      significant heavier than the wild hamsters. The lab males had the highest ADR,
      and it was independent of their high body mass (BM). The ADR of lab females and
      wild hamsters was linearly dependent of BM. The lab males had the highest faecal
      and blood CC, whereas the lab females had the lowest CC. In the open field, the
      lab hamsters began later to groom, groomed shorter, groomed less frequently,
      began later to rear, reared longer and reared less frequently. In the lab
      population, females reared more often and groomed longer than males. The sex
      differences in the behaviours of the lab population and the differences between
      the populations mirror the differences neither in the ADR nor in the CC. The
      founder effect and the breeding history of lab Syrian hamsters are discussed as
      causes of the differences between the studied populations.

PMID- 21077970
TI  - Detection and fine mapping of quantitative trait loci for bone traits on chicken
      chromosome one.
AB  - In broiler chickens, bone problems are an important welfare issue that has been
      linked to genetic selection for rapid growth. The objectives of this study were
      to identify and fine map quantitative trait loci (QTL) associated with bone
      traits. The Northeast Agricultural University resource population (NEAURP) being
      an F(2) population was used in this study, and a total of 17 bone traits were
      measured. In primary genome scan, the linkage map was constructed with 23
      microsatellite markers across the entire chicken chromosome 1. Seventeen QTLs for
      bone traits were identified and 12 of these were found between LEI0079 and
      ROS0025 (50.8 cM apart). To fine map the QTLs located between LEI0079 and
      ROS0025, more markers and more individuals were used and a new partial linkage
      map was constructed. The confidence intervals for QTLs were sharply narrowed down
      from 24.5~52.6 to 2.7~17.0 Mb. This study identified chromosome regions
      harbouring significant QTLs affecting bone traits and showed that the use of more
      markers and individuals could decrease the confidence interval of QTL
      effectively. The results provide a useful reference for further candidate gene
      research and MAS for bone traits.

PMID- 21077971
TI  - Genetic variations and sequences analysis of MTATP6 and MTATP8 genes among
      different Chinese pig breeds.
AB  - To investigate the genetic variations of mtATP6 and mtATP8 genes among different
      Chinese pig breeds, two fragments of 425 and 743 bp containing the whole coding
      region of mtATP8 and mtATP6 genes were amplified with 805 individuals from 23
      Chinese local pig breeds, three types of Chinese wild boars and three European
      pig breeds. Sequence comparison identified a total number of 17 substitutions
      including six variable sites in mtATP8 and eleven substitutions in mtATP6 gene.
      The restriction enzyme Fok I revealed four polymorphic sites (nt8086, 8176, 8514
      and 7784), and four RFLP haplotype patterns (A, B, C and D) were identified in
      mtATP6 and mtATP8 genes among all tested samples. Our data showed AC combined
      haplotype originated from Asia and BD was regarded as European origin. The
      average frequency of Asian mtDNA haplotypes was 38.3% across the investigated
      European breeds but varied within each breeds (13.3~76.7%). Phylogenetic analyses
      were performed also considering some published sequences in the databases; the
      sequences were divided into three distinct groups, denoted A, E1, and E2. The
      Asian AC haplotype existed among the European domestic pigs was fully consistent
      with the results of previous molecular studies and well-documented history. This
      study will help us to better understand the genetic variations of mitochondrial
      genes among different Chinese pig breeds.

PMID- 21077973
TI  - Scavenger receptor AI/II truncation, lung function and COPD: a large population
      based study.
AB  - OBJECTIVES: The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is
      involved in recognition and clearance of modified lipids and inhaled
      particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal
      collagen-like domain, which is essential for ligand recognition. We tested
      whether the Arg293X variant is associated with reduced lung function and risk of
      chronic obstructive pulmonary disease (COPD) in the general population. METHODS:
      We genotyped 48,741 individuals from the adult Danish general population for
      Arg293X, and recorded lung function and spirometry-defined COPD. RESULTS: Arg293X
      homozygotes (n = 5) and heterozygotes (n = 587), compared with noncarriers (n =
      48,149), had a 6% and 1% reduction in predicted percentage of forced vital
      capacity (FVC % predicted) (P = 0.05) and a nonsignificant 7% and 1% reduction in
      predicted percentage of forced expiratory volume in one second (FEV(1) %
      predicted) (P = 0.06), respectively. The Arg293X genotype interacted with gender
      (P = 0.004) and alpha(1) -antitrypsin MZ heterozygosity (P = 0.049), but not with
      superoxide dismutase-3 E1I1 heterozygosity (P = 0.11) in determining FEV(1) %
      predicted. Amongst men, FEV(1) % predicted and FVC % predicted were both reduced
      by 4% (P = 0.0004 and P = 0.0003, respectively) in Arg293X heterozygotes compared
      with noncarriers. Corresponding values were 14% (P = 0.03) and 11% (P = 0.04)
      amongst MZ heterozygotes, and 9% (P = 0.03) and 8% (P = 0.04) amongst E1I1
      heterozygotes, compared with noncarriers. Lung function did not differ between
      Arg293X heterozygotes and noncarriers amongst females or individuals without MZ
      and E1I1. Arg293X heterozygosity was associated with spirometry-defined COPD
      amongst men [odds ratio (95% confidence interval): 1.7 (1.1-2.4)], but not with
      COPD in the whole cohort or in any other subgroup. CONCLUSIONS: SRAI/II Arg293X
      heterozygotes have reduced lung function and increased COPD risk amongst men.
      They also have reduced lung function amongst individuals heterozygous for the
      alpha(1)-antitrypsin MZ and superoxide dismutase-3 E1I1 genotypes.

PMID- 21077972
TI  - Relationships between Podolic cattle breeds assessed by single nucleotide
      polymorphisms (SNPs) genotyping.
AB  - Italian Maremmana, Turkish Grey and Hungarian Grey breeds belong to the same
      Podolic group of cattle, have a similar conformation and recently experienced a
      similar demographic reduction. The aim of this study was to assess the
      relationship among the analysed Podolic breeds and to verify whether their
      genetic state reflects their history. To do so, approximately 100 single
      nucleotide polymorphisms (SNPs) were genotyped on individuals belonging to these
      breeds and compared to genotypes of individuals of two Italian beef breeds,
      Marchigiana and Piemontese, which underwent different selection and migration
      histories. Population genetic parameters such as allelic frequencies and
      heterozygosity values were assessed, genetic distances calculated and assignment
      test performed to evaluate the possibility of recent admixture between the
      populations. The data show that the physical similarity among the Podolic breeds
      examined, and particularly between Hungarian Grey and Maremmana cattle that
      experienced admixture in the recent past, is mainly morphological. The assignment
      of individuals from genotype data was achieved using Bayesian inference,
      confirming that the set of chosen SNPs is able to distinguish among the breeds
      and that the breeds are genetically distinct. Individuals of Turkish Grey breed
      were clearly assigned to their breed of origin for all clustering alternatives,
      showing that this breed can be differentiated from the others on the basis of the
      allelic frequencies. Remarkably, in the Turkish Grey there were differences
      observed between the population of Enez district, where in situ conservation
      studies are practised, and that of Bandirma district of Balikesir, where ex situ
      conservation studies are practised out of the original raising area. In
      conclusion, this study demonstrates that molecular data could be used to reveal
      an unbiased view of past events and provide the basis for a rational exploitation
      of livestock, suggesting appropriate cross-breeding plans based on genetic
      distance or breeding strategies that include the population structure.

PMID- 21077974
TI  - Uncoupling ecological innovation and speciation in sea snakes (Elapidae,
      Hydrophiinae, Hydrophiini).
AB  - The viviparous sea snakes (Hydrophiini) are by far the most successful living
      marine reptiles, with ~ 60 species that comprise a prominent component of shallow
      water marine ecosystems throughout the Indo-West Pacific. Phylogenetically nested
      within the ~ 100 species of terrestrial Australo-Melanesian elapids
      (Hydrophiinae), molecular timescales suggest that the Hydrophiini are also very
      young, perhaps only ~ 8-13 Myr old. Here, we use likelihood-based analyses of
      combined phylogenetic and taxonomic data for Hydrophiinae to show that the
      initial invasion of marine habitats was not accompanied by elevated
      diversification rates. Rather, a dramatic three to six-fold increase in
      diversification rates occurred at least 3-5 Myr after this transition, in a
      single nested clade: the Hydrophis group accounts for ~ 80% of species richness
      in Hydrophiini and ~ 35% of species richness in (terrestrial and marine)
      Hydrophiinae. Furthermore, other co-distributed lineages of viviparous sea snakes
      (and marine Laticauda, Acrochordus and homalopsid snakes) are not especially
      species rich. Invasion of the oceans has not (by itself) accelerated
      diversification in Hydrophiini; novelties characterizing the Hydrophis group
      alone must have contributed to its evolutionary and ecological success.

PMID- 21077976
TI  - Man's inhumanity to children.

PMID- 21077977
TI  - Relationship between childhood short stature and academic achievement in
      adolescents and young adults--a longitudinal study.
AB  - AIM: To determine if short stature at 14 or 21 years and patterns of 'catch-up'
      growth from 5 to 14 or 21 years are related to academic achievement in
      adolescents. METHODS: The Mater University of Queensland Study of Pregnancy is a
      longitudinal study of 7223 singleton infants born between 1981 and 1984. Data
      were available for cross-sectional analyses of 3785 adolescents of whom 2149 were
      seen as young adults. Longitudinal patterns of growth were examined for 2936
      subjects from 5 to 14 years and 1753 subjects from 5 to 21 years. RESULTS:
      Adolescents or young adults with height <10th centile had a lower mean Wide Range
      Achievement Test (WRAT) score in adolescence and at 21 years than those of normal
      height (2.7 and 3.0 points, respectively) and increased odds of a WRAT score <85
      (1.57 and 1.87, respectively) and learning difficulties (1.61 and 1.78,
      respectively). For growth patterns from 5 to 14 years, adolescents short at 5
      years, irrespective of height at 14 years, had a lower mean WRAT score and
      increased odds of WRAT score <85 and learning difficulties. However, for growth
      patterns from 5 to 21 years, only the group short at both ages had increased
      learning difficulties. CONCLUSIONS: Youth short at 14 years or at 21 years and
      those persistently short have an increased prevalence of academic difficulties.
      Catch-up growth by 21, although not 14 years, was associated with improved
      outcomes.

PMID- 21077978
TI  - The changing face of celiac disease: a girl with obesity and celiac disease.

PMID- 21077975
TI  - Probability and predictors of remission from life-time nicotine, alcohol,
      cannabis or cocaine dependence: results from the National Epidemiologic Survey on
      Alcohol and Related Conditions.
AB  - AIM: To estimate the general and racial/ethnic specific cumulative probability of
      remission from nicotine alcohol cannabis or cocaine dependence, and to identify
      predictors of remission across substances. DESIGN: Data were collected from
      structured diagnostic interviews using the Alcohol Use Disorder and Associated
      Disabilities Interview Schedule-DSM-IV version. SETTING: The 2001-2002 National
      Epidemiological Survey of Alcohol and Related Conditions (NESARC) surveyed a
      nationally representative sample from US adults (n = 43,093) selected in a three
      stage sampling design. PARTICIPANTS: The subsamples of individuals with life-time
      DSM-IV diagnosis of dependence on nicotine (n = 6937), alcohol (n = 4781),
      cannabis (n = 530) and cocaine (n = 408). MEASUREMENTS: Cumulative probability
      estimates of dependence remission for the general population and across
      racial/ethnic groups. Hazard ratios for remission from dependence. FINDINGS: Life
      time cumulative probability estimates of dependence remission were 83.7% for
      nicotine, 90.6% for alcohol, 97.2% for cannabis and 99.2% for cocaine. Half of
      the cases of nicotine, alcohol, cannabis and cocaine dependence remitted
      approximately 26, 14, 6 and 5 years after dependence onset, respectively. Males,
      Blacks and individuals with diagnosis of personality disorders and history of
      substance use comorbidity exhibited lower hazards of remission for at least two
      substances. CONCLUSIONS: A significant proportion of individuals with dependence
      on nicotine, alcohol, cannabis or cocaine achieve remission at some point in
      their life-time, although the probability and time to remission varies by
      substance and racial/ethnic group. Several predictors of remission are shared by
      at least two substances, suggesting that the processes of remission overlap. The
      lower rates of remission of individuals with comorbid personality or substance
      use disorders highlight the need for providing coordinated psychiatric and
      substance abuse interventions.

PMID- 21077979
TI  - Audit of Australian childhood obesity research funding 2005-2009.

PMID- 21077980
TI  - Acute colonic pseudo-obstruction in paediatric oncology patients.

PMID- 21077981
TI  - A case of neonatal coxsackie B virus brainstem encephalitis.

PMID- 21077982
TI  - Unilateral Horner's syndrome: an unusual childhood presentation.

PMID- 21077983
TI  - Influence of pigments and opacifiers on color stability of an artificially aged
      facial silicone.
AB  - PURPOSE: The aim of this study was to evaluate the influence of two pigments
      (ceramic powder and oil paint) and one opacifier (barium sulfate) on the color
      stability of MDX4-4210 facial silicone submitted to accelerated aging. MATERIALS
      AND METHODS: Sixty specimens of silicone were fabricated and divided into six
      groups--colorless (G1), colorless with opacifier (G2), ceramic (G3), ceramic with
      opacifier (G4), oil (G5), oil with opacifier (G6). All replicas were submitted to
      accelerated aging for 1008 hours. The evaluations of chromatic alteration through
      visual analysis and reflection spectrophotometry were carried out initially and
      after 252, 504, and 1008 hours of aging. The results were submitted to ANOVA and
      Tukey's test at 5% level of significance. RESULTS: All groups exhibited chromatic
      alteration (DeltaE > 0); however, this color alteration was not perceptible
      through visual analysis of the color. The pigmented groups with opacifier
      presented the lowest DeltaE values, with a statistical difference from the other
      groups. For the groups without opacifier, the group pigmented with oil paint
      exhibited the lowest DeltaE values in the different aging periods, with a
      statistical difference. Accelerated aging generated significant chromatic
      alterations in all groups after 252 hours, except for the colorless and oil
      groups, both with opacifier (G2 and G6). CONCLUSIONS: The opacifier protects
      facial silicones against color degradation, and oil paint is a stable pigment
      even without addition of opacifier.

PMID- 21077984
TI  - Real-time PCR assays compared to culture-based approaches for identification of
      aerobic bacteria in chronic wounds.
AB  - Chronic wounds cause substantial morbidity and disability. Infection in chronic
      wounds is clinically defined by routine culture methods that can take several
      days to obtain a final result, and may not fully describe the community of
      organisms or biome within these wounds. Molecular diagnostic approaches offer
      promise for a more rapid and complete assessment. We report the development of a
      suite of real-time PCR assays for rapid identification of bacteria directly from
      tissue samples. The panel of assays targets 14 common, clinically relevant,
      aerobic pathogens and demonstrates a high degree of sensitivity and specificity
      using a panel of organisms commonly associated with chronic wound infection.
      Thirty-nine tissue samples from 29 chronic wounds were evaluated and the results
      compared with those obtained by culture. As revealed by culture and PCR, the most
      common organisms were methicillin-resistant Staphylococcus aureus (MRSA) followed
      by Streptococcus agalactiae (Group B streptococcus) and Pseudomonas aeruginosa.
      The sensitivities of the PCR assays were 100% and 90% when quantitative and
      qualitative culture results were used as the reference standard, respectively.
      The assays allowed the identification of bacterial DNA from ten additional
      organisms that were not revealed by quantitative or qualitative cultures. Under
      optimal conditions, the turnaround time for PCR results is as short as 4-6 h.
      Real-time PCR is a rapid and inexpensive approach that can be easily introduced
      into clinical practice for detection of organisms directly from tissue samples.
      Characterization of the anaerobic microflora by real-time PCR of chronic wounds
      is warranted.

PMID- 21077985
TI  - Close cooperation between infectious disease physicians and attending physicians
      can result in better management and outcome for patients with Staphylococcus
      aureus bacteraemia.
AB  - Staphylococcus aureus bacteraemia (SAB) is a serious infection that demands
      prompt clinical attention for good outcome. To assess the impact of intervention
      by infectious diseases physicians (IDPs) in cases with SAB, a retrospective
      cohort study of patients with SAB was performed in a 1240-bed, university
      hospital in Japan, with the aim of comparing the management and outcome of
      patients during the initial and the latter half of the intervention period,.
      Three hundred and forty-six patients with SAB during the 7-year period, from 2002
      to 2008, were included, and 194 patients in the initial half of the period (from
      2002 to 2005) were compared with 152 patients in the later period (from 2006 to
      2008). There was no significant difference between the two groups with respect to
      patient's clinical background, although more patients in the later period were
      receiving immunosuppressive treatment. The proportion of methicillin resistant S.
      aureus was lower during the later period (56.2% vs. 43.3%; p 0.02).
      Echocardiography was used more frequently (37.1% vs. 64.5%; p < 0.001). Infective
      endocarditis and metastatic infections were diagnosed more frequently (10.8% vs.
      20.4%; p 0.01). Follow-up blood cultures were obtained more regularly (52.1% vs.
      73.7%; p <0.001) and therapy was more frequently administered for at least 14
      days (47.4% vs. 82.2%; p <0.001). The 30-day mortality improved during the
      intervention period (25.8% vs. 16.4%; p 0.04). The total number of blood cultures
      received by the laboratory increased annually and the total number of
      consultations increased by approximately 1.6-fold compared to 2002. Proactive
      intervention by IDPs raised awareness of optimal management of bacteraemia and
      improved the adherence to the standards of care, which subsequently resulted in
      an improvement in the outcome.

PMID- 21077986
TI  - Acute haematogenous prosthetic joint infection: prospective evaluation of medical
      and surgical management.
AB  - The optimum treatment for prosthetic joint infections has not been clearly
      defined. We report our experience of the management of acute haematogenous
      prosthetic joint infection (AHPJI) in patients during a 3-year prospective study
      in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a
      median age of 76 years, were diagnosed with AHPJI. The median infection-free
      period following joint replacement was 4.9 years. Symptoms were acute in all
      cases. A distant previous infection and/or bacteraemia were identified in 48%.
      The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14;
      Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty
      four (68%) patients were treated with a conservative surgical approach (CSA) with
      implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%)
      were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had
      persistent infection, five had re-infection, and two had an unknown evolution.
      Overall, the treatment failure rates were 57.8% in staphylococcal infections and
      14.3% in streptococcal infections. There were no failures in patients with Gram
      negative bacillary. By multivariate analysis, CSA was the only factor
      independently associated with treatment failure (OR 11.6; 95% CI 1.29-104.8). We
      were unable to identify any factors predicting treatment failure in CSA patients,
      although a Gram-negative bacillary aetiology was a protective factor. These data
      suggest that although conservative surgery was the only factor independently
      associated with treatment failure, it could be the first therapeutic choice for
      the management of Gram-negative bacillary and streptococcal AHPJI, and for some
      cases with acute S. aureus infections.

PMID- 21077987
TI  - Clinical evaluation of chronic nephrotoxicity of long-term cyclosporine A
      treatment in adult patients with steroid-dependent nephrotic syndrome.
AB  - AIM: Chronic nephrotoxicity of long-term cyclosporine A (CsA) treatment is a
      matter of concern in patients with steroid-dependent nephrotic syndrome (SDNS).
      METHODS: Twenty-eight adult NS patients (25, minimal-change nephrotic syndrome
      (NS); three, focal-segmental glomerulosclerosis) were divided into three groups.
      Group A was continuously treated with CsA for more than 5 years (143 +/- 40
      months, 1.3 +/- 0.4 mg/kg per day at final analysis, n = 12); group B had been
      previously treated with CsA (70 +/- 27 months, n = 6); and group C had been
      treated with corticosteroids alone (n = 10). The clinical variables related to
      chronic CsA nephrotoxicity were examined. RESULTS: In groups A and B, estimated
      glomerular filtration rate decreased from 86 +/- 22 and 107 +/- 17 to 83 +/- 23
      and 88 +/- 13 mL/min per 1.73 m(2) , respectively, at final analysis (both P <
      0.05). Serum magnesium levels in group A were significantly lower than those in
      group B or C (A, 1.78 +/- 0.16 mg/dL; B, 2.00 +/- 0.14 mg/dL; C, 2.03 +/- 0.10
      mg/dL; A vs B, C, P < 0.01), and a significant correlation between these and the
      duration of CsA treatment was found (r = -0.68, P < 0.001). There was a trend
      towards a correlation between the duration of CsA administration and urinary
      alpha1-microglobulin (r = 0.38, P = 0.07). CONCLUSION: Mild decrease in renal
      function and hypomagnesemia were found in adult SDNS patients with long-term CsA
      treatment. Careful monitoring of renal function, blood pressure and serum
      magnesium levels is necessary.

PMID- 21077988
TI  - The next generation: using new sequencing technologies to analyse gene
      regulation.
AB  - Next generation sequencing (NGS) has pushed back the limitations of prior
      sequencing technologies to advance genomic knowledge infinitely by allowing cost
      effective, rapid sequencing to become a reality. Genome-wide transcriptional
      profiling can be achieved using NGS with either Tag-Seq, in which short tags of
      cDNA represent a gene, or RNA-Seq, in which the entire transcriptome is
      sequenced. Furthermore, the level and diversity of miRNA within different tissues
      or cell types can be monitored by specifically sequencing small RNA. The
      biological mechanisms underlying differential gene regulation can also be
      explored by coupling chromatin immunoprecipitation with NGS (ChIP-Seq). Using
      this methodology genome-wide binding sites for transcription factors, RNAP II,
      epigenetic modifiers and the distribution of modified histones can be assessed.
      The superior, high-resolution data generated by adopting this sequencing
      technology allows researchers to distinguish the precise genomic location bound
      by a protein and correlate this with observed gene expression patterns.
      Additional methods have also been established to examine other factors
      influencing gene regulation such as DNA methylation or chromatin conformation on
      a genome-wide scale. Within any research setting, these techniques can provide
      relevant data and answer numerous questions about gene expression and regulation.
      The advances made by pairing NGS with strategic experimental protocols will
      continue to impact the research community.

PMID- 21077989
TI  - Secretory leukocyte protease inhibitor inhibits neutrophil apoptosis.
AB  - BACKGROUND AND OBJECTIVE: The secretory leukocyte protease inhibitor (SLPI) is a
      major anti-elastase barrier at the epithelial surfaces of upper respiratory
      tract. In addition to its anti-protease activity, SLPI has been shown to express
      anti-bacterial, anti-viral and anti-inflammatory properties. METHODS: We measured
      SLPI concentration in nasal lavage fluid of healthy volunteers after challenge
      with endotoxin (LPS) and evaluated SLPI effects in vitro on neutrophil
      chemotaxis, adhesion, cytokine (IL-8) release and apoptosis. RESULTS: SLPI
      concentration in nasal lavage (n = 9) 2, 6 and 24 h after the challenge with LPS
      (25 ug) increased from 32% to 238% compared with baseline (226 +/- 71 ng/mL). In
      vitro, SLPI (20-80 ug/mL) induced neutrophil chemotaxis (sixfold, P < 0.001) and
      decreased neutrophil apoptosis by 73% (P = 0.006), relative to controls. However,
      SLPI had no affect on IL-8 release or neutrophil adhesion to fibronectin. SLPI
      positive immunoreactivity was co-localized with neutrophils in lung specimens
      from patients with COPD. CONCLUSIONS: Our findings indicate upregulation of SLPI
      in response to LPS in nasal secretions and show anti-apoptotic effects of SLPI in
      primary human neutrophils suggesting a new role of SLPI during neutrophilic
      inflammation.

PMID- 21077990
TI  - Increased prevalence of primary drug-resistant pulmonary tuberculosis in
      immunocompromised patients.
AB  - BACKGROUND AND OBJECTIVE: Drug-resistant tuberculosis (DR-TB) is difficult and
      expensive to treat, and is associated with a higher rate of mortality. We
      conducted a long-term survey to compare the prevalence of primary drug
      resistance, adverse effects of drugs and duration of treatment in immunocompetent
      and immunocompromised patients. Factors associated with primary drug resistance
      were also investigated. METHODS: The patients studied had culture-confirmed
      pulmonary TB but had not previously received anti-TB treatment. These patients
      were divided into immunocompetent (IMCPe) and immunocompromised (IMCPr) groups.
      Baseline data, the prevalence of DR-TB, duration of treatment and adverse effects
      of drugs were analysed. The rates of resistance to individual first-line anti-TB
      drugs in the two groups and in subgroups of the IMCPr group were calculated.
      Multinomial regression analysis was performed to investigate the risk factors
      associated with primary DR-TB. RESULTS: Among the 394 patients, 159 (40.4%) were
      in the IMCPr group. The baseline data for the two groups were similar, except
      that the IMCPr group was slightly older. The prevalence of drug-resistance was
      higher in the IMCPr group (25.8% vs 17.0%, OR 1.69, 95% CI: 1.04-2.77),
      especially for isoniazid, rifampicin and streptomycin, and patients with liver
      cirrhosis, malignancies and those receiving immunosuppressants. The incidence of
      adverse drug effects was similar in the IMCPr and IMCPe groups. Multinomial
      regression analysis showed that being in the IMCPr group, and especially
      treatment with immunosuppressants, were independent risk factors for DR-TB.
      CONCLUSIONS: Immunocompromised patients with underlying diseases had an increased
      prevalence of primary pulmonary DR-TB but a similar incidence of drug-related
      adverse effects. Diagnosis and investigation of drug-resistance is important
      before initiating anti-TB treatment in this group of patients.

PMID- 21077991
TI  - Impaired swallow in COPD.

PMID- 21077992
TI  - Predicting factors of plural hospitalization with pneumonia in low-birthweight
      infants.
AB  - BACKGROUND: Children with a history of low birthweight (LBW) are often
      hospitalized with plural episodes of pneumonia after discharge from the neonatal
      intensive care unit. The aim of this study was to clarify the multiple factors
      predisposing them to developing three or more hospitalizations with pneumonia and
      whether the factors are related to their own prematurity. We also aimed to
      determine a predictable numerical formula for three or more episodes. METHODS:
      Fourteen patients with two hospitalizations with pneumonia were grouped into
      group A. Fourteen patients with at least three episodes during the same
      investigation period were grouped into group B. The quantification theory type
      III was employed to investigate the similarities among the items and the gravity
      of each attribution in the two groups. To evaluate the items of discrimination of
      both groups, six items were analyzed by the quantification theory type II.
      RESULTS: The dominant order of items contributing to the grouping was as follows:
      methicillin-resistant staphylococcus aureus detection (partial correlation
      coefficient = 0.5284), asthmatic attack (partial correlation coefficient =
      0.4138), severe motor and intellectual disability, Haemophilus influenzae,
      accompanying diseases and chronic lung disease. A predicting numerical formula
      was attained from these results. The success rate of discrimination was 85.7%.
      The six items seemed to be related to the patients' own prematurity. CONCLUSIONS:
      The authors emphasize that plural hospitalizations with pneumonia in the patients
      with LBW might be caused by the combined influence of six clinical factors as
      well as their own prematurity.

PMID- 21077993
TI  - New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury.
AB  - BACKGROUND: Pathogenesis of perinatal hypoxic-ischemic brain injury (HIE) is
      complex. In this study, we examined the role of neuroinflammation, oxidative
      stress and growth factors in perinatal hypoxic-ischemic brain damage. METHODS:
      Ninety neonates (>32 weeks' gestation) with perinatal HIE were enrolled
      prospectively. Perinatal HIE was categorized into three stages according to the
      Sarnat and Sarnat clinical scoring system and changes seen on amplitude
      integrated electroencephalography. Cerebrospinal fluid (CSF) for interleukin-6
      (IL-6) and glutathione peroxidase analysis was taken in the first 48 h of life
      and subsequent CSF for neuron-specific enolase (NSE) and vascular endothelial
      growth factor (VEGF) analysis 72 h after birth. Neurodevelopmental outcome was
      assessed at 12 months of corrected gestational age using the Denver Developmental
      Screening Test. RESULTS: Concentrations of NSE in CSF correlated with severity of
      HIE (P < 0.0001) and corresponded well with subsequent neurodevelopmental
      outcome. Concentrations of IL-6 in CSF were markedly increased in neonates with
      severe HIE (P < 0.0001) and those with subsequent neurological sequels, but were
      normal in the majority of neonates with mild and moderate HIE. Glutathione
      peroxidase activity in CSF was significant with the stage of HIE (P < 0.0001) and
      gestational age (P < 0.0001) and corresponded well with subsequent
      neurodevelopmental outcome. Advanced stage of HIE was associated with increased
      concentrations of VEGF in CSF (P < 0.0001). Neurological outcomes at 12 months of
      age correlated best with CSF level of NSE (P < 0.001) and IL-6 (P < 0.001).
      CONCLUSION: Our results suggest that neuroinflammation plays a principal role in
      perinatal hypoxic-ischemic brain damage and we postulate that oxidative stress
      and upregulation of VEGF might be important contributing factors in the
      pathogenesis of hypoxic-ischemic brain injury, particularly in preterm neonates.

PMID- 21077994
TI  - Hypothyroidism caused by iodine deficiency and iodine levels in enteral formulas.
AB  - BACKGROUND: A 4-year-old female patient was diagnosed with hypothyroidism caused
      by iodine deficiency. The patient's iodine levels in serum and urine were
      significantly low. The iodine concentration in the enteral formula was 1.6 ug/100
      kcal as measured by inductively coupled plasma mass spectrometry. The patient's
      iodine intake while receiving the enteral formula was calculated to be 16 ug/day,
      which is much lower than the recommended dietary reference intake of 80 ug for
      children aged 3-5 years. The purpose of this study was to assess iodine
      concentrations in 20 enteral nutritional formulas available in Japan in order to
      assess whether low iodine concentration is a characteristic of one specific
      formula or whether it is a more prevalent problem. METHODS: Iodine concentrations
      in 20 popular nutritional formulas available in Japan, for which iodine content
      is not indicated in the ingredient list, were analyzed with inductively coupled
      plasma mass spectrometry. RESULTS: Iodine concentrations were less than 5 ug/100
      kcal and less than 10 ug/100 kcal in 13 and 18 enteral nutritional formulas,
      respectively. CONCLUSIONS: Most of the enteral nutritional formulas analyzed had
      low iodine concentrations. These findings suggest that iodine deficiency is a
      likely outcome in patients who receive these formulas for a prolonged period.

PMID- 21077995
TI  - Medical visits of childhood cancer survivors in Japan: a cross-sectional survey.
AB  - BACKGROUND: Although more children with cancer continue to be cured, these
      survivors experience various late effects. Details of the medical visit behaviors
      of childhood cancer survivors (CCS) in adulthood remain to be elucidated.
      METHODS: In order to examine medical visits in the past and future of CCS, we
      performed a cross-sectional survey with self-rating questionnaires on medical
      visits of CCS compared with control groups (their siblings and the general
      population). RESULTS: Questionnaires were completed by 185 CCS, 72 of their
      siblings and 1000 subjects from the general population and the results were
      analyzed. Mean ages at this survey and the duration after therapy completions of
      CCS were 23 and 12 years, respectively. We found that the previous treatment
      hospitals (where CCS were treated for their cancer) were the most commonly
      visited medical facilities for the CCS group (74% for female patients and 64% for
      male patients) and more than half of the CCS preferred to continue visiting the
      previous treatment hospital with enough satisfaction in Japan. The multivariate
      analysis showed that female sex and relapse were significantly associated with
      the past visits to the previous treatment hospital and that the CCS with brain
      tumors or bone/soft tissue sarcomas and CCS with any late effects tended to
      continue the relationships with the hospital. In addition female sex was also
      significantly associated with desired future visits to the previous treatment
      hospital. On the other hand, the married CCS tended to be disinclined to visit
      the hospital it in the future. CONCLUSIONS: In order to optimize risk-based care
      and promote health for CCS after adulthood, we should discuss the medical
      transition with CCS and their parents.

PMID- 21077997
TI  - Phase I/II study of a 3-week cycle of irinotecan and S-1 in patients with
      advanced colorectal cancer.
AB  - The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan is
      expected to be a promising regimen for advanced colorectal cancer. This study was
      performed to determine the maximum tolerated dose (MTD) and recommended dose (RD)
      of irinotecan combined with S-1 in a 3-week cycle regimen and to observe the
      safety and efficacy for patients with previously untreated advanced colorectal
      cancer. Eighty milligrams per m(2) of S-1 was given orally for 14 consecutive
      days and escalated doses of irinotecan were administered on days 1 and 8 every 3
      weeks in the phase I trial. Forty patients were treated at the RD during the
      phase II trial. Forty-three patients were enrolled between February 2005 and
      March 2007. The dose-limiting toxicity was diarrhea and abdominal pain. The MTD
      of irinotecan was 100 mg/m(2) and the RD was determined to be 80 mg/m(2) of
      irinotecan combined with 80 mg/m(2) of S-1. The phase II trial showed that 22 of
      40 patients achieved a complete or partial response and eight had stable disease.
      The overall response rate was 55.0%. The median progression-free survival time
      and median survival time were 6.7 and 21 months, respectively. There were no
      treatment-related deaths. The main toxicities were leukopenia, neutropenia,
      anorexia and diarrhea. This study suggests the combination of irinotecan and S-1
      repeated every 3 weeks is tolerable and effective for patients with previously
      untreated advanced colorectal cancer.

PMID- 21078000
TI  - The role of emotional brain processing during sleep in depression.
AB  - ACCESSIBLE SUMMARY: * Explores current research illuminating the physiological
      mechanisms contributing the relationship of sleep dysfunction and depression. *
      Investigates the crucial role of sleep in the affective modulation of brain
      functioning. * Describes the relationship between emotional brain processing
      during rapid eye movement and depression. * Points to the use of multi
      therapeutic approaches for treatment with emphasis on positive behavioural
      imagery therapies. ABSTRACT: This review synthesizes some of the most current
      investigative research to illuminate the physiological mechanisms contributing to
      the relationship between sleep dysfunction and depression. Major depression has
      consistently been linked to sleep abnormalities and insomnia is a robust risk
      factor in the initiating and development of depression. Recent neurobiological
      findings indicate the crucial role of sleep in the affective modulation of brain
      functioning. Studies have demonstrated that sleep in major depression is
      characterized by a reduction in slow wave sleep, interruptions in sleep
      continuity, longer periods of rapid eye movement (REM) sleep including a
      shortening of REM latency (i.e. the time between sleep onset and the occurrence
      of the first REM period), as well as an increase in REM density. The failure of
      sleep dependant emotional brain processing in REM sleep that seems to occur in
      depression, support the development and fostering of clinical depression. How
      depression likely interplays with these sleep processes points to the use of
      multi-therapeutic approaches for treatment with emphasis on positive behavioural
      imagery therapies.

PMID- 21077998
TI  - Obtusilactone A and (-)-sesamin induce apoptosis in human lung cancer cells by
      inhibiting mitochondrial Lon protease and activating DNA damage checkpoints.
AB  - Several compounds from Cinnamomum kotoense show anticancer activities. However,
      the detailed mechanisms of most compounds from C. kotoense remain unknown. In
      this study, we investigated the anticancer activity of obtusilactone A (OA) and (
      )-sesamin in lung cancer. Our results show that human Lon is upregulated in non
      small-cell lung cancer (NSCLC) cell lines, and downregulation of Lon triggers
      caspase-3 mediated apoptosis. Through enzyme-based screening, we identified two
      small-molecule compounds, obtusilactone A (OA) and (-)-sesamin from C. kotoense,
      as potent Lon protease inhibitors. Obtusilactone A and (-)-sesamin interact with
      Ser855 and Lys898 residues in the active site of the Lon protease according to
      molecular docking analysis. Thus, we suggest that cancer cytotoxicity of the
      compounds is partly due to the inhibitory effects on Lon protease. In addition,
      the compounds are able to cause DNA double-strand breaks and activate
      checkpoints. Treatment with OA and (-)-sesamin induced p53-independent DNA damage
      responses in NSCLC cells, including G(1) /S checkpoint activation and apoptosis,
      as evidenced by phosphorylation of checkpoint proteins (H2AX, Nbs1, and Chk2),
      caspase-3 cleavage, and sub-G(1) accumulation. In conclusion, OA and (-)-sesamin
      act as both inhibitors of human mitochondrial Lon protease and DNA damage agents
      to activate the DNA damage checkpoints as well induce apoptosis in NSCLC cells.
      These dual functions open a bright avenue to develop more selective chemotherapy
      agents to overcome chemoresistance and sensitize cancer cells to other
      chemotherapeutics.

PMID- 21078001
TI  - Inpatient staff perceptions in providing care to individuals with co-occurring
      mental health problems and illicit substance use.
AB  - ACCESSIBLE SUMMARY: This paper reports on a piece of research which is summarized
      below. * This research explored how mental health inpatient staff, (including
      nurses, doctors and other professional disciplines) experience caring for
      patients who both have mental health problems and who use illicit drugs. (Illicit
      drugs are illegal drugs which incur a criminal prosecution for possession and/or
      use). The results of the study were gathered from questionnaires and interviews
      which asked staff about their viewpoints and experiences. * The questionnaire
      results included a section which measured staff attitude towards patients who use
      illicit drugs and who have mental health problems. Staff who had received
      training in how to work with people with these problems were found to have a less
      negative attitude towards these patients. The length of time staff members had
      worked in their posts or had worked in a particular setting did not have any
      effect on their attitude. For example, their attitude was not more or less
      negative towards patients with these problems. * Ten members of staff were
      interviewed to find out more in-depth information about their viewpoints and
      experiences. Overall, these staff members reported a lack of training, difficulty
      in accessing support and problematic issues within the teams they worked. * This
      paper highlights the importance of training to support staff in working with
      mental health patients who use illicit drugs; and how this affects staff attitude
      positively towards patients with these problems. ABSTRACT: The extent of illicit
      substance use within inpatient mental health settings is becoming a major cause
      of concern. This poses growing challenges not only for the management of
      inpatient units, but also for providing continuity of care. Service users with co
      occurring substance use are more likely to disengage from services. The process
      of engagement can be hindered by negative attitudes of staff. This study aimed to
      identify and explore multidisciplinary staff attitudes and experiences in caring
      for inpatients with co-occurring ill-mental health problems and illicit substance
      use. A questionnaire incorporating the Drug and Drugs Problems Perceptions
      Questionnaire (DDPPQ) was used with a non-probability sample of 84
      multidisciplinary staff working on nine mental health units. Semi-structured
      interviews were then carried out with 10 members of staff. Overall, respondents
      reported: lack of training; difficulty in accessing support structures; and
      problematic issues with multidisciplinary decision making and processes. The
      DDPPQ results showed that staff who had received training held less negative
      attitudes towards illicit substance users regardless of their length of clinical
      work experience or type of work setting. Recommendations are made about the
      importance of training and staff support for the development of less negative
      attitudes towards this client group.

PMID- 21078002
TI  - Locked doors: a survey of patients, staff and visitors.
AB  - ACCESSIBLE SUMMARY: * Locking of psychiatric wards doors is more frequent, but
      the impact is unknown. * Staff patients and visitors returned a questionnaire
      about the issue. * Patients did not like the door being locked as much as staff,
      and being on a locked ward was associated with greater rejection of the practice.
      * Staff working on locked wards were more positive about it than those who did
      not. ABSTRACT: Locking the door of adult acute psychiatric wards has become
      increasingly common in the UK. There has been little investigation of its
      efficacy or acceptability in comparison to other containment methods. We surveyed
      the beliefs and attitudes of patients, staff and visitors to the practice of door
      locking in acute psychiatry. Wards that previously participated in a previous
      study were contacted and sent a questionnaire. A total of 1227 responses were
      obtained, with the highest number coming from staff, and the smallest from
      visitors. Analysis identified five factors (adverse effects, staff benefits,
      patient safety benefits, patient comforts and cold milieu). Patients were more
      negative about door locking than the staff, and more likely to express such
      negative judgments if they were residing in a locked ward. For staff, being on a
      locked ward was associated with more positive judgments about the practice. There
      were significant age, gender and ethnicity effects for staff only. Each group saw
      the issue of locked doors from their own perspective. Patients registered more
      anger, irritation and depression as a consequence of locked doors than staff or
      visitors thought they experienced. These differences were accentuated by the
      actual experience of the ward being locked.

PMID- 21078004
TI  - Relation of assertiveness and anxiety among Iranian University students.
AB  - ACCESSIBLE SUMMARY: * The findings from the present study revealed that less than
      30% of nursing and midwifery students have high assertiveness and only half of
      them have low anxiety. * Assertiveness and anxiety have negative correlations in
      nursing and midwifery students and affect the mental health and educational and
      occupational performance of the students. * Many factors such as years of
      education and working while studying influence the level of assertiveness in the
      students. * The anxiety in students had a significant relation with the father's
      level of education, family income, etc. ABSTRACT: The simultaneous existence of
      low assertiveness and high anxiety in nursing and midwifery students leads to the
      disruption of study performance. There exists little information concerning their
      assertiveness. The purpose of this study was to determine the relation of
      assertiveness and anxiety in nursing and midwifery students. In this
      correlational, cross-sectional study, 173 nursing students (68 males and 105
      females) and 77 midwifery students were recruited from the Tehran University of
      Medical Sciences in Iran. Data were collected using a questionnaire including
      personal-social factors, the Spielberger Trait Anxiety Inventory and the
      Assertion Inventory of Gambrill and Richey. More than half of the nursing and
      midwifery students (59.5% and 59.7%, respectively) had moderate assertiveness.
      Also, 43.3% and 36.4% of them had moderate and high levels of anxiety. Pearson
      correlation test revealed that assertiveness and anxiety had negative
      correlations in nursing (r=-0.51, P < 0.001) and midwifery (r=-0.449, P < 0.001)
      students. Some demographic variables had significant correlations with
      assertiveness and anxiety among the students. Considering the relation of
      assertiveness and anxiety and its effects on mental health and educational and
      occupational performance, students should be informed of the required skills for
      positive interaction with others and to increase assertiveness and decrease
      anxiety.

PMID- 21078003
TI  - Crisis resolution and home treatment: structure, process, and outcome - a
      literature review.
AB  - ACCESSIBLE SUMMARY: * During the last ten years there has been a major change in
      developing mental health services generally, and crisis resolution and home
      treatment (CRHT) services especially. Many Western countries have made a shift in
      perspective from in-hospital care to home treatment. The new approach is based on
      treating people who experience mental health crises in their homes instead of
      through hospitalization. * Most of the published articles on CRHT focus on
      structural issues pertaining to the development of home treatment services, and
      on macro-level outcomes such as cost-effectiveness and admission rates. These
      have political, economic, and practical implications. Few articles describe
      clinical intervention methods used in home treatment. * This paper explores how
      home treatment is described as an essential intervention method in crisis
      resolution at home in relation to three key characteristics of CRHT, which are
      being mobile, working in the service user's home, and working together with the
      person's family and network. * There remains a need for further research
      describing specific characteristics of home treatment, different clinical
      interventions that are used by CRHT teams, and the directions with which clinical
      interventions need to be developed further. It is critical to investigate what
      makes the interventions of the CRHT teams different from the hospital care, and
      how this affects the service users, the family and the networks, and the
      professionals. ABSTRACT: The objective of this paper is to explore and
      systematize the existing knowledge regarding the structure, process, and outcome
      of crisis resolution and home treatment (CRHT) as a form of community mental
      health service. Data sources are published peer-reviewed articles. Our study
      selection is systematic search for peer-reviewed articles written in English and
      Norwegian published between January 2000 and December 2008. Data are extracted
      from review of published articles on the subject of CRHT team and home treatment.
      We identified 35 articles including 6 reviews, consisting of quantitative and
      qualitative studies. The knowledge regarding CRHT focuses on three areas: (1)
      structure in terms of the standards, organization, and development; (2) process
      in terms of clinical interventions; and (3) outcome in relation to cost
      effectiveness and admission rates. While the structural issues were presented and
      discussed a great deal, there is a paucity of articles on clinical intervention
      methods in home treatment as well as a limited attention on outcomes at the micro
      level. There is a need for further studies regarding the clinical work of CRHT
      teams from the home treatment perspective.

PMID- 21078005
TI  - Eating attitude in the obese patients: the evaluation in terms of relational
      factors.
AB  - ACCESSIBLE SUMMARY: * Obesity has become an important health problem because of
      the gradually increasing incidence seen within all age groups. People with
      obesity problems are affected lifespan and health negatively. * Obesity can be
      described as disease that affects lifespan and health negatively, because of body
      fat deposition. * The eating attitudes, body perception, strategies for coping
      with stress in patient being treated for obesity and investigated the
      relationship between their eating attitudes and socio-demographic
      characteristics, body perceptions and strategies of coping with stress. *
      Misperception of the body and the ability to solve the problem increased as
      eating attitude defects increased. A positive correlation was between the eating
      attitude defects and habitude of pursing social support and ability of coping.
      ABSTRACT: Obesity, a complex disease, involves many psychological problems
      besides eating disorders. In this study, we aimed to examine the relationship
      between the eating attitude and body perception, which is thought to affect the
      eating attitude in the patients diagnosed as obese, the ability to solve the
      problem, the strategy of coping with stress and some socio-demographic features.
      A total of 99 adults aged between 20 and 68 years, who were examined in the
      Polyclinic of Endocrinology and Metabolism Diseases, Ege University, Turkiye,
      constituted the sample of the study. Eating Attitude Test, The Body Perception
      Scale and The Scale of Coping with Strategies were used in order to collect the
      data. Misperception of the body and the ability to solve the problem increased as
      eating attitude defects increased. A positive correlation was determined between
      the eating attitude defects and the habitude of pursuing social support and the
      ability of coping.

PMID- 21078006
TI  - Relationship challenges and relationship maintenance activities following
      disclosure of transsexualism.
AB  - ACCESSIBLE SUMMARY: * Transsexual persons are increasing their visibility in
      society, and health care providers and others (such as social workers) will be
      called upon to help with issues that transsexual persons face. Challenges that
      face transsexual persons often include issues involving relationships.
      Psychiatric and mental health nurses and other caregivers can increase their
      therapeutic skills in working with couples that include transsexual persons by
      becoming aware of these challenges and subsequent activities that can help with
      them. * This research study looks at couple relationships in which one partner
      reveals male-to-female transsexual identity. These are relationships that were
      established as man-woman and now will transition into relationships that include
      a male-to-female person and a female partner. * Common challenges for these
      couples include issues related to: (1) sexual identity and relationship
      uncertainty; (2) male-to-female transition decision making; and (3) presenting in
      public. * Relationship maintenance activities that helped the couples in the
      study maintain and strengthen their relationships through these challenges
      include: (1) communication; (2) self-talk (for example, putting the situation in
      perspective); (3) social networks; (4) positive interactions; (5) impression
      management (for example, managing displays of affection in public); and (6)
      social activism. ABSTRACT: This qualitative study describes the relational
      dynamics that help sustain relationships of couples that include male-to-female
      transsexual persons (MTF) and their natal female partners (NF) following
      disclosure of transsexualism. Relationship challenges and relationship
      maintenance activities are identified. Each partner in 17 MTF-NF couples
      participated in individual surveys and interviews. The data were coded for themes
      related to relationship challenges and activities. MTF-NF couples experience
      challenges within the contexts of their relationships and of society. These
      challenges include: (1) sexual identity and relationship uncertainty; (2) male-to
      female transition decision making; and (3) public presentation. Relationship
      maintenance activities enabled the study couples to maintain and strengthen their
      relationships through these challenges. These activities include: (1)
      communication; (2) self-talk; (3) social networks; (4) positivity; (5) impression
      management; and (6) social activism. Via this report, psychiatric and mental
      health nurses can increase their therapeutic skills in working with MTF-NF
      couples.

PMID- 21078007
TI  - Immigrant and refugee women's post-partum depression help-seeking experiences and
      access to care: a review and analysis of the literature.
AB  - ACCESSIBLE SUMMARY: * This literature review on post-partum depression (PPD)
      presents an analysis of the literature about PPD and the positive and negative
      factors, which may influence immigrant and refugee women's health seeking
      behaviour and decision making about post-partum care. * A critical review of
      English language peer-reviewed publications from 1988 to 2008 was done by the
      researchers as part of a qualitative research study conducted in a western
      province of Canada. The overall goal of the study is to raise awareness and
      understanding of what would be helpful in meeting the mental health needs of the
      immigrant and refugee women during the post-partum period. * Several online
      databases were searched: Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), PsycINFO, MEDLINE (Ovid), EBM Reviews - Cochrane Database of Systematic
      Reviews. * Review of the literature suggests: 1 Needs, issues and specific risk
      factors for PPD among immigrant and refugee women have been limited. 2
      Descriptive accounts regarding culture and PPD are found in the literature but
      impact of cultural factors upon PPD has not been well studied. 3 Few studies look
      at how social support, gender, and larger institutions or organizational
      structures may affect immigrant and refugee women's help-seeking and access to
      mental health care services. 4 More research is needed to hear the immigrant and
      refugee women's ideas about their social support needs, the difficulties they
      experience and their preferred ways of getting help with PPD. ABSTRACT: This
      review and analysis of the literature is about the phenomenon of post-partum
      depression (PPD) and the barriers and facilitators, which may influence immigrant
      and refugee women's health seeking behaviour and decision making about post
      partum care. As part of a qualitative research study conducted in a western
      province of Canada a critical review of English language peer-reviewed
      publications from 1988 to 2008 was undertaken by the researchers. The overall
      goal of the study is to raise awareness and understanding of what would be
      helpful in meeting the mental health needs of the immigrant and refugee women
      during the post-partum period. Several online databases were searched: Cumulative
      Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, MEDLINE (Ovid),
      EBM Reviews - Cochrane Database of Systematic Reviews. Findings suggest: (1)
      needs, issues and specific risk factors for PPD among immigrant and refugee women
      have been limited; (2) descriptive accounts regarding culture and PPD are found
      in the literature but impact of cultural factors upon PPD has not been well
      investigated; (3) few studies examine how social support, gender, institutional
      and organizational structures present barriers to the women's health seeking
      behaviour; and (4) additional research is required to evaluate immigrant and
      refugee women's perspectives about their social support needs, the barriers they
      experience and their preferred support interventions.

PMID- 21078008
TI  - 'Psychic assaults and frightened clinicians' deserves better.

PMID- 21078009
TI  - Susceptibility of community-acquired pathogens to antibiotics in Africa and Asia
      in neonates--an alarmingly short review.
AB  - OBJECTIVE: To assess the susceptibility of community-acquired pathogens in
      neonatal sepsis to commonly prescribed antibiotics in sub-Saharan Africa and Asia
      since 2002. METHODS: Literature review in PubMed and Embase. Susceptibility was
      estimated for pathogens individually and stratified by region. Isolates were also
      classified into Gram positive and Gram negative pathogens to estimate their
      pooled susceptibility. RESULTS AND CONCLUSIONS: Only nine studies met the
      inclusion criteria. The available data indicated poor susceptibility to almost
      all commonly used antibiotics in pathogens such as Staphylococcus aureus and
      Klebsiella spp. Only Streptococcus pneumoniae exhibited good susceptibility to
      all drugs other than cotrimoxazole. The extreme scarcity of data prevents drawing
      any firm conclusions beyond the urgent need for more studies to identify the best
      treatments for neonatal sepsis in the developing world.

PMID- 21078011
TI  - Comment on 'clarification regarding the distribution of bigeye tuna Thunnus
      obesus in the Atlantic Ocean, including British waters'.

PMID- 21078013
TI  - Morphology, testes development and behaviour of unusual triploid males in
      microchromosome-carrying clones of Poecilia formosa.
AB  - In a microchromosome-carrying laboratory stock of the normally all-female Amazon
      molly Poecilia formosa triploid individuals were obtained, all of which
      spontaneously developed into males. A comparison of morphology of the external
      and internal insemination apparatus and the gonads, sperm ploidy and behaviour,
      to laboratory-bred F(1) hybrids revealed that the triploid P. formosa males,
      though producing mostly aneuploid sperm, are partly functional males that differ
      mainly in sperm maturation and sexual motivation from gonochoristic P. formosa
      males.

PMID- 21078010
TI  - Attributes of response in depressed patients switched to treatment with
      duloxetine.
AB  - BACKGROUND: This study was designed to assess clinical and functional outcomes
      associated with switching to duloxetine treatment in patients with major
      depressive disorder (MDD) experiencing emotional and painful physical symptoms in
      their current episode. METHODS: In this 8-week, multinational, multicentre,
      single-arm, open-label clinical trial, 242 MDD patients were switched to
      duloxetine 60 mg/day after selective serotonin reuptake inhibitor (SSRI) or
      serotonin and norepinephrine reuptake inhibitor (SNRI) treatment. The primary
      analysis compared mean change from baseline in Brief Pain Inventory-Modified
      Short Form (BPI-SF) interference score between initial responders [>= 50%
      reduction from baseline on the 17-item Hamilton Depression Rating Scale
      (HAMD(17)) Maier subscale] and initial non-responders after 4 weeks. Initial
      responders continued with duloxetine 60 mg/day. Initial non-responders received
      duloxetine 120 mg/day for the remaining 4 weeks. Depression, pain, anxiety and
      functional outcomes were also compared after 8 weeks. RESULTS: BPI-SF
      interference decreased from baseline in initial responders (n = 108) and initial
      non-responders (n = 85) after 4 weeks of duloxetine treatment, with greater
      reductions in initial responders [BPI-SF mean difference in reduction: 1.01 (95%
      CI 0.42-1.61); p < 0.001]. Reductions in pain interference favouring initial
      responders were also apparent after 8 weeks [0.68 (95% CI: 0.03-1.33); p =
      0.042]. Depression, pain, anxiety and function improved over 8 weeks across
      patient groups. CONCLUSIONS: Elements of core mood and pain are important
      residual symptoms following poor treatment response in MDD. Early improvement in
      these symptoms after switching to duloxetine indicated an increased chance of
      functional recovery.

PMID- 21078014
TI  - The effect of stimulus type and background noise on hearing abilities of the
      round goby Neogobius melanostomus.
AB  - The auditory abilities of the round goby Neogobius melanostomus were quantified
      using auditory evoked potential recordings, using tone bursts and conspecific
      call stimuli. Fish were tested over a range of sizes to assess effects of growth
      on hearing ability. Tests were also run with and without background noise to
      assess the potential effects of masking in a natural setting. Neogobius
      melanostomus detected tone bursts from 100 to 600 Hz with no clear best frequency
      in the pressure domain but were most sensitive to 100 Hz tone stimuli when
      examined in terms of particle acceleration. Responses to a portion of the N.
      melanostomus call occurred at a significantly lower threshold than responses to
      pure tone stimulation. There was no effect of size on N. melanostomus hearing
      ability, perhaps due to growth of the otolith keeping pace with growth of the
      auditory epithelium. Neogobius melanostomus were masked by both ambient noise and
      white noise, but not until sound pressure levels were relatively high, having a 5
      10 dB threshold shift at noise levels of 150 dB re 1 uPa and higher but not at
      lower noise levels.

PMID- 21078015
TI  - Reproductive biology of the starry smooth-hound shark Mustelus asterias:
      geographic variation and implications for sustainable exploitation.
AB  - Examination of the reproductive biology of Mustelus asterias in the north-east
      Atlantic Ocean highlighted apparent geographical variation in maturity, fecundity
      and ovarian cycle between Atlantic and Mediterranean populations. The stretch
      total length (L(ST) ) and age at 50% maturity for Atlantic males and females were
      estimated at 78 cm L(ST) and 4-5 years and 87 cm L(ST) and 6 years, respectively.
      Size at maturity of females was considerably smaller than in Mediterranean
      specimens (96 cm L(ST) ). Ovarian fecundity ranged from eight to 27 oocytes and
      uterine fecundity from six to 18 embryos. The gestation period was c. 12 months,
      followed by a resting period of c. 12 months, resulting in a biennial cycle.
      Females stored sperm in the oviducal gland and, unlike Mediterranean specimens,
      no uterine compartments were observed in Atlantic specimens. This study reveals
      the existence of strong, possibly adaptive, divergence in life-history traits in
      an elasmobranch, whose northern populations may be more susceptible to
      overexploitation than previously believed.

PMID- 21078017
TI  - Variation with reproductive status of PGE2receptor immunoreactivities in the
      Bostrichthys sinensis olfactory system.
AB  - The role of PGE(2) as a putative sex pheromone in Chinese black sleeper
      Bostrichthys sinensis was investigated, using immunocytochemistry and how the
      immunoreactivities of the prostaglandin E(2) (PGE(2) ) receptor subtypes EP(1) ,
      EP(2) , EP(3) and EP(4) varied with reproductive status in the olfactory system
      was determined. The results showed that PGE(2) receptors were present in the
      whole of the olfactory system of B. sinensis, and that the number of receptors
      was linked to the reproductive status of the fish. The densities of EP(1)
      immunoreactivity in the olfactory epithelium of mature fish were significantly (P
      < 0.01) higher than those in immature fish of both sexes, and the densities of
      EP(2) and EP(3) immunoreactivities in mature fish were higher (but not
      significantly) than those in immature fish of both sexes. In the olfactory nerve,
      the density of EP(2) immunoreactivity in mature fish was higher (but not
      significantly) than that in immature fish in both sexes. In the olfactory bulb,
      the densities of EP(1-4) immunoreactivities in mature females were significantly
      (P < 0.05 or <0.01) higher than those in immature females, and the density of
      EP(4) immunoreactivity in mature males was significantly (P < 0.01) higher than
      that in immature males. As far as is known, the present study is the first report
      of the immunoreactivities of PGE(2) receptor subtypes in the olfactory system of
      a teleost, and offers new findings regarding the role of PGE(2) as sex pheromone
      and hormone in the reproductive behaviour and pheromonal communication of B.
      sinensis.

PMID- 21078016
TI  - Riverine environmental characteristics and seasonal habitat use by adult Sakhalin
      taimen Hucho perryi.
AB  - The study identified seasonal habitat use by endangered adult Sakhalin taimen
      Hucho perryi and the environmental characteristics of their habitat (water depth,
      amount of riparian forest and sinuosity). Fifteen adult H. perryi with acoustic
      tags were tracked by towing an acoustic receiver with a canoe in the Bekanbeushi
      River system in eastern Hokkaido Island, Japan, during each month from late April
      to late November 2008. Individuals mainly used midstream (shallower than
      downstream) habitats in all seasons. These locations were generally characterized
      by relatively dense riparian forests and high sinuosity, indicating the presence
      of pools. In spring, individuals used habitats with less riparian forest cover
      compared to mean value of the river channel. From spring to autumn, adult H.
      perryi selected limnologically complex habitats with meandering channels. From
      summer to autumn, individuals selected habitats with more riparian forest cover.
      The inverse relationship between H. perryi detection and riparian forest area in
      spring was a result of seasonal defoliation in deciduous riparian forests.

PMID- 21078018
TI  - Age validation and growth of bluenose Hyperoglyphe antarctica using the bomb
      chronometer method of radiocarbon ageing.
AB  - Age validation of bluenose Hyperoglyphe antarctica was sought using the
      independent bomb chronometer procedure. Radiocarbon ((14) C) levels were measured
      in core micro-samples from 12 otoliths that had been aged using a zone count
      method. The core (14) C measurement for each fish was compared with the value on
      a surface water reference curve for the calculated birth year of the fish. There
      was good agreement, indicating that the line-count ageing method described here
      is not substantially biased. A second micro-sample was also taken near the edge
      of nine of the otolith cross-sections to help define a bomb-carbon curve for
      waters deeper than 200-300 m. There appears to be a 10 to 15 year lag in the time
      it takes the (14) C to reach the waters where adult H. antarctica are
      concentrated. The maximum estimated age of this species was 76 years, and females
      grow significantly larger than males. Von Bertalanffy growth curves were
      estimated, and although they fit the available data reasonably well, the lack of
      aged juvenile fish results in the K and t(0) parameters being biologically
      meaningless. Consequently, curves that are likely to better represent population
      growth were estimated by forcing t(0) to be -0.5.

PMID- 21078019
TI  - Using rapid assessment and demographic methods to evaluate the effects of fishing
      on Heterodontus portusjacksoni off far-eastern Victoria, Australia.
AB  - A rapid semi-quantitative ecological risk assessment method (productivity and
      susceptibility analysis) indicated that, despite its low biological productivity,
      the Port Jackson shark Heterodontus portusjacksoni is at low risk to all fishing
      methods in far-eastern Victoria, Australia, under the present fishing practices,
      because of its low catch susceptibility. The risk to this population, however,
      would increase if the shark gillnet fishery operating in the region were to
      retain the species as a by-product. Demographic analysis indicated that the
      species has medium intrinsic population growth rate and potential rebound in
      comparison with other chondrichthyan species, juveniles have higher elasticity
      than mature females and both juvenile and mature females have higher elasticities
      than hatchlings. Because of its low biological productivity and moderate
      resilience to the effects of fishing, cautious management measures will be
      necessary to ensure the sustainable use of H. portusjacksoni if its marketing
      increases in the future. Information on the dynamics of a population that is
      valuable to provide management advice can be obtained through demographic
      methods, but rapid assessment methods can also provide complementary information
      on the effects of fishing by considering the catch susceptibility of the
      population to each fishing method.

PMID- 21078020
TI  - Analysis of rainbow trout Oncorhynchus mykiss epidermal mucus and evaluation of
      semiochemical activity for polar filament discharge in Myxobolus cerebralis
      actinospores.
AB  - As myxozoan actinospores are stimulated by fish epidermal mucus to attach to
      their hosts via extrusion of filaments from specialized organelles, the polar
      capsules, mucus components were tested for discharge triggering activity on
      Myxobolus cerebralis actinospores. Using various methodological approaches, a
      selective exclusion of candidate substances based on experimental outcome is
      provided and the physiochemical traits of the putative agents are explored to
      create a basis for the isolation of the host recognition chemostimuli. Activity
      was detected in compounds that can be characterized as small molecular,
      amphiphilic to slightly hydrophobic organic substances. They were separable by
      chromatographic methods using reversed phase C18 supports. An active fraction was
      isolated by solid phase extraction comprising at least nine UV-detectable
      constituents as shown by thin-layer chromatography. By means of biochemical
      fractionation and analysis of host fish mucus, non-volatile inorganic
      electrolytes, all volatiles, free L-amino acids, glycoproteins, bound and free
      hexoses, sialic acids, glycans, proteins, urea, amines and inositols were shown
      not to trigger polar filament discharge. The results contribute to the
      identification of the attachment host cues and enable a more focused laboratory
      activation of myxozoan actinospores.

PMID- 21078021
TI  - Habitat use and behavioural ecology of the juveniles of two sympatric
      damselfishes (Actinopterygii: Pomacentridae) in the south-western Atlantic Ocean.
AB  - Spatial distribution, microhabitat use and territorial and feeding behaviours
      were compared between the juveniles of two sympatric territorial damselfishes
      Stegastes variabilis and Stegastes fuscus on a small tropical reef in the south
      western Atlantic Ocean. Juvenile S. variabilis were most abundant at sites
      subject to stronger hydrodynamics and with mixed benthic cover, whereas juvenile
      S. fuscus were most abundant at sheltered sites with dense turf algae cover. No
      differences regarding feeding habits were detected, with both species
      preferentially feeding on turf algae. Also, despite similarities in territory
      area and agonistic encounter rates, the identity and proportion of intruders
      involved in agonistic interactions differed significantly between species. These
      interdependent traits suggest strong asymmetric competition, with juvenile S.
      fuscus dominating high-quality sites and evicting juvenile S. variabilis to low
      quality, marginal areas of the reef.

PMID- 21078023
TI  - Size-mediated response to public cues of predation risk in a tropical stream
      fish.
AB  - In order to investigate any size-dependent differences between behavioural
      patterns, wild-caught Hart's rivulus Rivulus hartii of varying sizes were exposed
      to chemical alarm cues extracted from the skin of conspecifics or heterospecific
      Poecilia reticulata, or a tank water control, in a series of laboratory trials.
      In response to conspecific alarm cues, R. hartii subjects of the range of body
      sizes tested exhibited consistent, size-independent antipredator behaviours that
      were characterized by decreased locomotory activity and foraging levels and
      increased refuging behaviour. Conversely, focal R. hartii demonstrated
      significant size-dependent trends in response to heterospecific alarm cues, with
      smaller individuals exhibiting antipredator responses and larger individuals
      shifting their behaviour to increased levels of activity consistent with a
      foraging, or predatory, response. These results show that the behavioural
      responses of individual R. hartii to publicly available chemical alarm cues from
      heterospecifics are mediated by the size of the receiver.

PMID- 21078022
TI  - Changes in Atlantic salmon Salmo salar mucus components following short- and long
      term handling stress.
AB  - This study examined changes in Atlantic salmon Salmo salar epidermal mucus
      proteins following short- and long-term handling stress. Short-term stress
      consisted of a single removal of fish from water for 15 s with long-term stress
      consisting of daily removal of fish from water for 15 s over 21 days. In the long
      term handling stress study, there was a high level of individual variability with
      respect to mucus alkaline phosphatase, cathepsin B and lysozyme activities, with
      no correlation to treatment group. There was limited or no positive correlation
      between lysozyme, cathepsin B or alkaline phosphatase activities and plasma
      cortisol. There was a significant difference in lysozyme activity for both
      control and stressed fish at day 21 compared to other sampling days. In the short
      term study, there was again high variability in mucus enzyme activities with no
      difference observed between groups. Immunoblotting also showed variability in
      mucus actin breakdown products in both short- and long-term handling stress
      studies. There appeared, however, to be a shift towards a more thorough breakdown
      of actin at day 14 in the stressed group. This shift suggested changes in mucus
      proteases in response to long-term handling stress. In summary, there were
      correlations of some mucus enzyme/protein profiles with stress or cortisol;
      however, the variability in S. salar mucus enzyme levels and actin fragmentation
      patterns suggested other triggers for inducing changes in mucus protein
      composition that need to be investigated further in order to better understand
      the role of mucus in the response of S. salar to external stressors.

PMID- 21078024
TI  - Differentiation and adaptive radiation of amphibious gobies (Gobiidae:
      Oxudercinae) in semi-terrestrial habitats.
AB  - During several surveys made in the region of the lower Fly River and delta, Papua
      New Guinea, nine species of oxudercine gobies (Gobiidae: Oxudercinae) were
      recorded: Boleophthalmus caeruleomaculatus, Oxuderces wirzi, Periophthalmodon
      freycineti, Periophthalmus darwini, Periophthalmus novaeguineaensis,
      Periophthalmus takita, Periophthalmus weberi, Scartelaos histophorus and Zappa
      confluentus. An exploratory multivariate analysis of their habitat conditions
      discriminated five guilds, differentially distributed in habitats with different
      quantities of environmental water and three guilds corresponding to different
      levels of salinity. A partial correspondence between phylogenetic and ecological
      categories suggested the presence of parallel adaptive radiations within
      different genera. In particular, the species found in the most terrestrial
      habitats (P. weberi) was also found in the widest range of conditions, suggesting
      that colonization of extreme semi-terrestrial and freshwater habitats by this
      species was facilitated by eurytypy. It is proposed that these findings provide
      insight into convergent adaptations for the vertebrate eco-evolutionary
      transition from sea to land.

PMID- 21078025
TI  - Glycoproteins histochemistry of the gills of Odontesthes bonariensis (Teleostei,
      Atherinopsidae).
AB  - The histochemistry of glycoproteins (GP) in the mucous cells of the gills of the
      silverside Odontesthes bonariensis was identified with: (1) oxidizable vicinal
      diols; (2) sialic acid and some of their chain variants, carbon 7 ((7) C), carbon
      8 ((8) C) or carbon 9 ((9) C); (3) sialic acid residues without O-acyl
      substitution and with O-acyl substitution at (7) C, (8) C or (9) C; (4) carboxyl
      groups and (5) sulphate groups. A battery of seven biotinylated lectins allowed
      GPs sugar residues to be distinguished. Mucous cells showed the presence of
      neutral, sulphated and sialylated GPs. Dolichos biflorus agglutinin (DBA) and
      Glycine max agglutinin (SBA) showed strong positive staining; Arachis hypogaea
      agglutinin (PNA), Ricinus communis agglutinin-I (RCA-I) and Triticum vulgaris
      agglutinin (WGA) showed moderate staining, while Ulex europaeus agglutinin-I (UEA
      I) was completely negative.

PMID- 21078026
TI  - Effects of habitat modification on coastal fish assemblages.
AB  - The purpose of this study was to assess the influence of anthropogenic
      modification of coastal habitats on fish assemblages in Taiwan, comparing the
      abundance, species richness and taxonomic composition of fishes on natural v.
      artificial habitats. While there was no significant variation in the abundance or
      richness of fishes between natural and artificial habitats, the species
      composition of fishes in artificial habitats was significantly different from
      that of natural habitats. Natural reefs were characterized by greater abundance
      of Stethojulis spp. (Labridae), Abudefduf spp. (Pomacentridae) and Thalassoma
      spp. (Labridae), whereas anthropogenic habitats were dominated by Parupeneus
      indicus (Mullidae), Pempheris oualensis (Pempheridae) and Parapriacanthus
      ransonneti (Pempheridae). In general, it appears that specialist reef-associated
      species are being replaced with fishes that are much more generalist in their
      habitat-use. The loss of natural coastal habitats may threaten some species that
      cannot live in anthropogenically altered habitats, though the overall abundance
      and diversity of coastal fishes was not significantly different between natural
      and artificial habitats in Taiwan.

PMID- 21078027
TI  - Seasonal occurrence and population structure of the broadnose sevengill shark
      Notorynchus cepedianus in coastal habitats of south-east Tasmania.
AB  - Research longline sampling was conducted seasonally from December 2006 to
      February 2009 to investigate the occurrence and population structure of the
      broadnose sevengill shark Notorynchus cepedianus in coastal areas of south-east
      Tasmania. Notorynchus cepedianus showed a consistent temporal trend in seasonal
      occurrence in Norfolk Bay characterized by high abundances in summer to near
      absence in winter. This pattern was less pronounced in the Derwent Estuary, where
      fish were still caught during winter. The absence of smaller total length (L(T) )
      classes (<80 cm) from the catches suggests that N. cepedianus are not using these
      coastal habitats as nursery areas. Of the 457 individuals tagged, 68 (15%) were
      recaptured. Time at liberty ranged from 6 days to almost 4 years and all but one
      of the recaptures were caught in its original tagging location, suggesting site
      fidelity. The large number of N. cepedianus in these coastal systems over summer
      indicates that these areas are important habitats for this species and that N.
      cepedianus may have a significant influence on community dynamics through both
      direct and indirect predator-prey interactions.

PMID- 21078028
TI  - Effects of food deprivation on refuge use and dispersal in juvenile North Sea
      houting Coregonus oxyrinchus under experimental conditions.
AB  - This study tested the influence of energetic state on refuge use and dispersal in
      juvenile North Sea houting Coregonus oxyrinchus in an artificial stream. Food
      deprived fish spent more time outside refuges than well-fed fish; however, the
      well-fed fish initiated dispersal faster than the food-deprived fish. The results
      may indicate state-dependent refuge use and dispersal in C. oxyrinchus.

PMID- 21078029
TI  - Preliminary results on the reproduction of a deep-sea snailfish Careproctus
      rhodomelas around the active hydrothermal vent on the Hatoma Knoll, Okinawa,
      Japan.
AB  - Deep-sea snailfish Careproctus rhodomelas were collected from an active
      hydrothermal vent using a remotely operated vehicle (R.O.V. Hyper-dolphin) and a
      pressurized device (Deep-Aquarium). Careproctus rhodomelas exhibited a
      cystovarian-type ovary containing a small number of developing oocytes at
      different stages, suggesting that the fish is a batch-spawner that spawns large
      eggs (c. 6.0 mm) several times within its life span. In vitro culture of the
      oocytes in the presence of human chorionic gonadotropin showed that oestradiol
      17beta production fluctuated with oocyte development, suggesting that the oocytes
      were at the vitellogenic stage.

PMID- 21078030
TI  - Rainbow trout Oncorhynchus mykiss consume less energy when swimming near
      obstructions.
AB  - The effect of obstructions in steady flow on swimming by rainbow trout
      Oncorhynchus mykiss was examined in a respirometry swim tunnel to test the
      prediction that fish interacting with obstructions require less energy to hold
      station. When an obstruction was present, O. mykiss altered the kinematics of
      swimming and the rate of oxygen consumption was significantly reduced. The fish
      employed both entrainment and Karman gait swimming strategies, permitting greater
      locomotor efficiency.

PMID- 21078031
TI  - Mother-offspring isotope fractionation in two species of placentatrophic sharks.
AB  - Stable-isotope values of a scalloped hammerhead Sphyrna lewini and blacktip shark
      Carcharhinus limbatus and their respective embryos were analysed. Embryos of both
      species were enriched in delta(15) N compared to their mothers (0.82 and
      0.880/00, respectively), but fractionation of delta(13) C varied. Embryonic S.
      lewini were enriched (1.000/00) in delta(13) C while C. limbatus were depleted
      (0.270/00) relative to their mothers.

PMID- 21078033
TI  - Water flow drives biodiversity by mediating rarity in marine benthic communities.
AB  - In aquatic ecosystems, water flow mediates the delivery of reproductive
      propagules, competition and predation, each of which may have contrasting effects
      on biodiversity. Here, we show that water flow has a net positive effect on the
      biodiversity of benthic invertebrate communities in three biogeographic regions.
      In Palau and Alaska, flow velocity predicted 55-91% of the variance in species
      richness in natural communities. In experimental communities in Alaska and Maine,
      enhanced water flow treatments resulted in higher levels of species density
      (+56%) and richness (+74%), which were predicted by the abundance of locally rare
      species. Additionally, the richness of recruitment was higher in experimentally
      enhanced flows (+46%). Thus, the data suggest that flow drives diversity by
      mediating the delivery of rare species in multiple biogeographic regions.
      Consequently, flow velocity should be included in future developments of
      diversity theory and conservation strategy.

PMID- 21078034
TI  - Effects of experimental shifts in flowering phenology on plant-pollinator
      interactions.
AB  - Climate change has led to phenological shifts in flowering plants and insect
      pollinators, causing concern that these shifts will disrupt plant-pollinator
      mutualisms. We experimentally investigated how shifts in flowering onset affect
      pollinator visitation for 14 native perennial plant species, six of which have
      exhibited shifts to earlier flowering over the last 70 years and eight of which
      have not. We manipulated flowering onset in greenhouses and then observed
      pollinator visitation in the field. Five of six species with historically
      advanced flowering received more visits when flowering was experimentally
      advanced, whereas seven of eight species with historically unchanged flowering
      received fewer visits when flowering earlier. This pattern suggests that species
      unconstrained by pollinators have advanced their flowering, whereas species
      constrained by pollinators have not. In contrast to current concern about
      phenological mismatches disrupting plant-pollinator mutualisms, mismatches at the
      onset of flowering are not occurring for most of our study species.

PMID- 21078035
TI  - Epibacterial community patterns on marine macroalgae are host-specific but
      temporally variable.
AB  - Marine macroalgae are constantly exposed to epibacterial colonizers. The
      epiphytic bacterial patterns and their temporal and spatial variability on host
      algae are poorly understood. To investigate the interaction between marine
      macroalgae and epiphytic bacteria, this study tested if the composition of
      epibacterial communities on different macroalgae was specific and persisted under
      varying biotic and abiotic environmental conditions over a 2-year observation
      time frame. Epibacterial communities on the co-occurring macroalgae Fucus
      vesiculosus, Gracilaria vermiculophylla and Ulva intestinalis were repeatedly
      sampled in summer and winter of 2007 and 2008. The epibacterial community
      composition was analysed by denaturing gradient gel electrophoresis (DGGE) and
      16S rRNA gene libraries. Epibacterial community profiles did not only differ
      significantly at each sampling interval among algal species, but also showed
      consistent seasonal differences on each algal species at a bacterial phylum
      level. These compositional patterns re-occurred at the same season of two
      consecutive years. Within replicates of the same algal species, the composition
      of bacterial phyla was subject to shifts at the bacterial species level, both
      within the same season but at different years and between different seasons.
      However, 7-16% of sequences were identified as species specific to the host alga.
      These findings demonstrate that marine macroalgae harbour species-specific and
      temporally adapted epiphytic bacterial biofilms on their surfaces. Since several
      algal host-specific bacteria were highly similar to other bacteria known to
      either avoid subsequent colonization by eukaryotic larvae or to exhibit potent
      antibacterial activities, algal host-specific bacterial associations are expected
      to play an important role for marine macroalgae.

PMID- 21078036
TI  - Role of positron emission tomography in urological oncology.
AB  - * Positron emission tomography (PET) is a diagnostic tool using radiotracers to
      show changes in metabolic activities in tissues. We analysed the role of PET and
      PET/computed tomography (CT) in the diagnosis, staging, and follow-up of
      urological tumours. * A critical, non-structured review of the literature of the
      role of PET and PET/CT in urological oncology was conducted. * PET and PET/CT can
      play a role in the management of urological malignancies. For prostate cancer,
      the advances in radiotracers seems promising, with novel radiotracers yielding
      better diagnostic and staging results than 18F-fluorodeoxyglucose (18F-FDG). In
      kidney cancer, PET and PET/CT allow a proper diagnosis before the pathological
      examination of the surgical specimen. For testis cancer, PET and PET/CT have been
      shown to be useful in the management of seminoma tumours. In bladder cancer,
      these scans allow a better initial diagnosis for invasive cancer, while detecting
      occult metastases. * PET and its combined modality PET/CT have shown their
      potential in the diagnosis of urological malignancies. However, further studies
      are needed to establish the role of PET in the management of these diseases.
      Future applications of PET may involve fusion techniques such as magnetic
      resonance imaging with PET.

PMID- 21078037
TI  - Role of positron emission tomography in urological oncology.

PMID- 21078038
TI  - Role of positron emission tomography in urological oncology.

PMID- 21078039
TI  - p53-Associated Parkin-like cytoplasmic protein (Parc) short-interfering RNA
      (siRNA) alters p53 location and biology of Peyronie's disease fibroblasts.
AB  - OBJECTIVE * To evaluate the impact of p53-associated Parkin-like cytoplasmic
      protein (Parc) short-interfering RNA (siRNA) on the location of p53 as well as
      the biology of Peyronie's disease (PD) plaque-derived fibroblasts after Parc
      knockdown. PATIENTS AND METHODS * Plaque tissue was excised from men with stable
      PD undergoing penile reconstructive surgery and used to produce cultured PD
      plaque-derived fibroblasts. * Immunofluorescence (IF) and reverse transcription
      polymerase chain reaction (RT-PCR) were then used to define the location of p53
      and Parc before and after siRNA. * Nuclear fractionation studies were used to
      assess the chronology of translocation of p53 from cytoplasm to nucleus on Parc
      knockdown. * The terminal transferase dUTP Nick end labelling (TUNEL) assay was
      used to assess the apoptotic indices of the PD fibroblasts after Parc knockdown.
      RESULTS * IF and PCR showed high cytoplasmic levels of p53 and Parc before siRNA.
      On IF, there was little or no p53 present within the nucleus before Parc
      knockdown. * After Parc siRNA, IF showed translocation of p53 to the fibroblast
      nucleus, while Parc levels dropped significantly, but what Parc remained was
      confined to the cytoplasm with none present in the nucleus. * Nuclear
      fractionation studies using RT-PCR confirmed this translocation phenomenon and
      showed the chronology of the event. All p53 had moved from the cytoplasm to the
      nucleus within 16 h of Parc siRNA. * On TUNEL assay, apoptotic indices increased
      dramatically after Parc siRNA. CONCLUSIONS * These data prove that Parc is a
      cytoplasmic anchor for p53 in PD plaque-derived fibroblasts and may be the
      primary cause of the stabilization and defunctionalization of p53 in these cells.
      * These findings support Parc as a novel target for PD pharmacotherapy, perhaps
      using human siRNA technologies once commercially available.

PMID- 21078041
TI  - In vivo microwave-induced porcine kidney thermoablation: results and perspectives
      from pilot study of a new probe?

PMID- 21078043
TI  - Current prospects for the chemoprevention of prostatic cancer.

PMID- 21078044
TI  - Improving patient safety in urology.

PMID- 21078045
TI  - Mainz pouch continent cutaneous diversion.

PMID- 21078046
TI  - Early release of pedicles and posterior development of the 'Veil of Aphrodite' in
      robotic-assisted laparoscopic prostatectomy (RALP).

PMID- 21078047
TI  - Low dose of ketoconazole in patients with prostate adenocarcinoma resistant to
      pharmacological castration.
AB  - OBJECTIVE: * To assess the efficacy of ketoconazole in patients with castration
      resistant prostate cancer (CRPC). PATIENTS AND METHODS: * From April 2008 to
      November 2009, 37 patients with CRPC have been treated with ketoconazole. The
      primary endpoint was the prostate-specific antigen (PSA) response; the secondary
      endpoints were progression-free survival and safety profile. * Ketoconazole was
      administered by oral route at a dose of 200 mg every 8 h continuous dosing until
      the onset of serious adverse events or disease progression. * The study was based
      on a two-step design with an interim efficacy analysis carried out on the first
      12 patients accrued. RESULTS: * Main characteristics of population were: median
      age 75 years (range 60-88); baseline mean PSA 28.8 ng/mL (4.3-1000); 30 patients
      previously challenged with at least two lines of hormone therapy; 15 patients
      previously treated with chemotherapy. * Biochemical responses accounted for: two
      complete responses (5%), six partial responses (16%), 13 patients with stable
      disease (35%), and 14 with progressive disease (38%). Of 15 patients resistant to
      chemotherapy, overall disease control (complete plus partial responses plus
      stable disease) was recorded in seven of them. * Treatment was feasible without
      inducing grade 3-4 adverse events. The most common grade 1-2 adverse events were
      asthenia (27%), vomiting (8%) and abdominal pain (8%). CONCLUSION: * Treatment
      with low-dose ketoconazole is feasible and well tolerated. The efficacy was
      satisfactory in patients previously treated with chemotherapy.

PMID- 21078048
TI  - Oncological outcomes after laparoscopic and open radical nephroureterectomy:
      results from an international cohort.
AB  - OBJECTIVE: * To compare oncological outcomes in patients undergoing open radical
      nephroureterectomy (ONU) with those in patients undergoing laparoscopic radical
      nephroureterectomy (LNU). PATIENTS AND METHODS: * A total of 773 patients
      underwent radical nephroureterectomy at nine centres worldwide; 703 patients
      underwent ONU and 70 underwent LNU. * Demographic, perioperative and oncological
      outcome data were collected retrospectively. * Statistical analysis of data was
      performed using chi-squared, Mann-Whitney U- and log-rank tests, and Cox
      regression analyses. * The median (interquartile range) follow-up for the cohort
      was 34 (15-65) months. RESULTS: * The two groups were well matched for tumour
      stage, presence of lymphovascular invasion (LVI) and concomitant carcinoma in
      situ (CIS). * There were more high-grade tumours (77.1% vs. 56.3%; P < 0.001) but
      fewer lymph node positive patients (2.9% vs. 6.8%; P= 0.041) in the LNU group. *
      Estimated 5-year recurrence-free survival (RFS) was 73.7% and 63.4% for the ONU
      and LNU groups, respectively (P= 0.124) and estimated 5-year cancer-specific
      survival (CSS) was 75.4% and 75.2% for the ONU and LNU groups, respectively (P=
      0.897). * On multivariable analyses, which included age, gender, race, previous
      endoscopic treatment for bladder cancer, technique for distal ureter management,
      tumour location, pathological stage, grade, lymph node status, LVI and
      concomitant CIS, the procedure type (LNU vs. ONU) was not predictive of RFS
      (Hazard ratio [HR] 0.80; P= 0.534) or CSS (HR 0.96; P= 0.907). CONCLUSION: * The
      present study is the second large, independent, multicentre cohort to show
      oncological equivalence between ONU and LNU for well selected patients with upper
      urinary tract urothelial cancer, and the first to suggest parity for the
      techniques in patients with unfavourable disease.

PMID- 21078049
TI  - Evidence-based medicine: comparative analysis of luteinizing hormone-releasing
      hormone analogues in combination with external beam radiation and surgery in the
      treatment of carcinoma of the prostate.
AB  - What's known on the subject? and What does the study add? Luteinizing hormone
      releasing hormone analogues are a cornerstone in the management of many clinical
      situations in prostate cancer patients. The multiplicity of drugs make it
      difficult to decide which is the best drug to prescribe to each patient. Whether
      or not the different luteinizing hormone-releasing hormone analogues belong to
      the same drug class is only merely supposed. This study adds a systematic review
      of the literature in order to determine whether or not the luteinizing hormone
      releasing hormone analogues available for prescription belong to the same drug
      class (same family, similar chemical structure, mechanism of action, and
      efficacy). The current evidence available is not enough to support a presumed
      drug class effect of the various analogues in the treatment of prostate
      carcinoma. OBJECTIVE: * To study whether luteinizing hormone-releasing hormone
      (LHRH) analogues are agents of the same pharmacological class, i.e. whether they
      have the same clinical effect, using an evidence-based medicine approach.
      MATERIAL AND METHODS: * We reviewed the evidence on the alleged 'drug class
      effect' among analogues and the existing bibliographic support for their use in
      various medical indications. We used PubMed as the main search source. Evidence
      level and degree of recommendation were assigned to each conclusion based on the
      'Scottish Intercollegiate Guidelines Network'. RESULTS: * There are no studies
      designed to answer the question of class effect between LHRH analogues or
      agonists. Reviews and meta-analyses have been performed on many other issues
      related to therapeutic management either with analogues alone, or in combination
      with radiation therapy and surgery. * Direct comparisons do not allow definitive
      conclusions to be reached. Indirect evidence is obtained from randomized studies
      comparing the different LHRH analogues with other treatments used to obtain
      androgen deprivation. Other issues related to pharmacokinetics and
      pharmacodynamics that can support either the existence or non-existence of class
      effect were evaluated. CONCLUSION: * The current available evidence is not enough
      to support a presumed class effect of the drug among the different analogues in
      the treatment of prostate carcinoma in its various clinical situations.

PMID- 21078050
TI  - A new patient-focused approach to the treatment of metastatic renal cell
      carcinoma: establishing customized treatment options.
AB  - What's known on the subject? and What does the study add? * Six targeted agents-
      sorafenib, sunitinib, pazopanib, bevacizumab, temsirolimus and everolimus--have
      been approved for the treatment of advanced renal cell carcinoma (RCC) based on
      evidence from large randomized controlled trials (RCTs). However, no head-to-head
      trials have been conducted to evaluate the relative efficacy of these agents in
      this setting. * Patient populations included in clinical trials do not accurately
      reflect the wider population of patients with RCC, as certain subgroups, such as
      the elderly or those with co-morbidities, are typically under-represented. * The
      optimum choice of therapy should be based on patient characteristics, nature of
      disease, and history and aims of therapy; however, there is currently no clear
      guidance for physicians in this decision-making process. * A patient-focussed
      schema has been developed that acknowledges nine different patient-, disease-,
      and treatment-related factors relevant to clinical decision-making, and provides
      a visual indication of the strength of evidence with which a particular agent can
      be recommended for use in specific subgroups. * To demonstrate the applicability
      of this tool, a review of all available evidence (published articles, congress
      presentations and personal communications) for sorafenib in RCC was conducted by
      a panel of experts, findings from which showed that sorafenib can be recommended
      for use in various subgroups of differing age, prognosis, performance status,
      tumour burden and distribution, treatment history and co-morbidity. * This
      patient-focussed approach has broad application and can be used to assess other
      agents and tumour types. Randomized controlled trials (RCTs) show that six
      targeted agents--sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab and
      pazopanib--improve outcome in advanced renal cell carcinoma (RCC). The
      populations enrolled in the pivotal phase III studies differed, and, to date, no
      head-to-head comparisons allow us to judge relative efficacy and tolerability.
      Populations recruited to RCTs under-represent certain patient subtypes, notably
      the elderly and those with comorbidities. Choosing the agent most appropriate in
      a specific case requires that we take into account the characteristics of the
      patient, the nature of their disease, and the history and aims of therapy. Data
      from expanded access programmes and clinical experience may be as relevant as the
      results of RCTs when making this difficult decision. To show how different
      sources of data can be integrated, we propose a schema that acknowledges nine
      patient-, disease-, and treatment-related factors relevant to clinical decision
      making and provides an easily understood visual indication of the strength with
      which a particular agent can be recommended for use in specific subgroups of
      patients. As an example, we show how this tool shows the suitability of sorafenib
      in RCC subpopulations of differing age, prognosis, performance status, tumour
      burden and distribution, treatment history, and comorbidity. This patient-focused
      approach has broad application to other agents and tumour types.

PMID- 21078051
TI  - Improved foreign gene expression in plants using a virus-encoded suppressor of
      RNA silencing modified to be developmentally harmless.
AB  - Endeavours to obtain elevated and prolonged levels of foreign gene expression in
      plants are often hampered by the onset of RNA silencing that negatively affects
      target gene expression. Plant virus-encoded suppressors of RNA silencing are
      useful tools for counteracting silencing but their wide applicability in
      transgenic plants is limited because their expression often causes harmful
      developmental effects. We hypothesized that a previously characterized
      tombusvirus P19 mutant (P19/R43W), typified by reduced symptomatic effects while
      maintaining the ability to sequester short-interfering RNAs, could be used to
      suppress virus-induced RNA silencing without the concomitant developmental
      effects. To investigate this, transient expression in Nicotiana benthamiana was
      used to evaluate the ability of P19/R43W to enhance heterologous gene expression.
      Although less potent than wt-P19, P19/R43W was an effective suppressor when used
      to enhance protein expression from either a traditional T-DNA expression cassette
      or using the CPMV-HT expression system. Stable transformation of N. benthamiana
      yielded plants that expressed detectable levels of P19/R43W that was functional
      as a suppressor. Transgenic co-expression of green fluorescent protein (GFP) and
      P19/R43W also showed elevated accumulation of GFP compared with the levels found
      in the absence of a suppressor. In all cases, transgenic expression of P19/R43W
      caused no or minimal morphological defects and plants produced normal-looking
      flowers and fertile seed. We conclude that the expression of P19/R43W is
      developmentally harmless to plants while providing a suitable platform for
      transient or transgenic overexpression of value-added genes in plants with
      reduced hindrance by RNA silencing.

PMID- 21078052
TI  - Antihypertensive activity of transgenic rice seed containing an 18-repeat
      novokinin peptide localized in the nucleolus of endosperm cells.
AB  - Novokinin (Arg-Pro-Leu-Lys-Pro-Trp, RPLKPW) is a new potent antihypertensive
      peptide based on the sequence of ovokinin (2-7) derived from ovalbumin. We
      previously generated transgenic rice seeds in which eight novokinin were fused to
      storage protein glutelins (GluA2 and GluC) for expression. Oral administration of
      these seeds to spontaneously hypertensive rats (SHRs) reduced systolic blood
      pressures at a dose of 1 g seed/kg of SHR. Here, 10- or 18-tandem repeats of
      novokinin with an endoplasmic reticulum (ER) retention signal (Lys-Asp-Glu-Leu,
      KDEL) at the C terminus were directly expressed in rice under the control of the
      glutelin promoter containing its signal peptide. Only small amounts of the 18
      repeat novokinin accumulated, and it was unexpectedly deposited in the nucleolus.
      This abnormal intracellular localization was explained by an endogenous signal
      for nuclear localization. The GFP reporter protein fused to this sequence
      targeted to nuclei by a transient assay using onion epidermal cells. Transgenic
      seed expressing the 18-repeat novokinin exhibited significantly higher
      antihypertensive activity after a single oral dose to SHR even at one-quarter the
      amount (0.25 g/kg) of the transgenic rice seed expressing the fusion construct;
      though, its novokinin content was much lower (1/5). Furthermore, in a long-term
      administration for 5 weeks, even a smaller dose (0.0625 g/kg) of transgenic seeds
      could confer antihypertensive activity. This high antihypertensive activity may
      be attributed to differences in digestibility of expressed products by
      gastrointestinal enzymes and the unique intracellular localization. These results
      indicate that accumulation of novokinin as a tandemly repeated structure in
      transgenic rice is more effective than as a fusion-type structure.

PMID- 21078054
TI  - Maternal morbidity and near miss in the community: findings from the 2006
      Brazilian demographic health survey.
AB  - OBJECTIVE: To obtain an estimate of the prevalence of potentially life
      threatening maternal conditions and near-miss events in Brazil, and to explore
      the factors associated with these complications. DESIGN: A demographic health
      survey (DHS) focusing on reported maternal complications. SETTING: Data from the
      five geographical regions of Brazil. POPULATION: A total of 5025 women with at
      least one live birth in the 5-year reference period preceding their interview in
      the DHS. METHODS: A secondary analysis of the 2006 Brazilian DHS database was
      carried out using a validated questionnaire to evaluate the occurrence of
      maternal complications and related key interventions. According to a pragmatic
      definition, any woman reporting the occurrence of eclampsia, hysterectomy, blood
      transfusion or admission to the intensive care unit was considered as having
      experienced a near-miss event. Associations between the sociodemographic
      characteristics of the women and severe maternal morbidity were evaluated. MAIN
      OUTCOME MEASURES: Proportions and ratios of complications and related
      interventions defined as maternal near miss in pregnancy, and estimated risk
      factors for maternal morbidities. RESULTS: Around 22% of women reported
      complications during pregnancy. The prevalence of maternal near miss in Brazil,
      using the pragmatic definition, was 21.1 per 1000 live births. An increased risk
      of severe maternal morbidity was found in women aged >=40 years and in those with
      low levels of education. CONCLUSIONS: Nearly 70,000 maternal near-miss cases and
      approximately 750,000 cases with potentially life-threatening conditions are
      estimated to occur in Brazil per year. A pragmatic definition of maternal near
      miss was useful to obtain more reliable information at the community level. This
      approach could be used to gather information on maternal morbidity in settings in
      which such data are not routinely collected.

PMID- 21078055
TI  - Risk factors for small-for-gestational-age infants by customised birthweight
      centiles: data from an international prospective cohort study.
AB  - OBJECTIVE: To identify clinical and ultrasound variables associated with the
      birth of small-for-gestational-age (SGA) infants by customised centiles,
      subclassified according to whether their mothers were normotensive or developed
      hypertensive complications. DESIGN: Prospective, multicentre cohort study.
      SETTING: Participating centres of the Screening for Pregnancy Endpoints (SCOPE)
      study in Auckland, New Zealand, Adelaide, Australia, Manchester and London, UK,
      and Cork, Ireland. POPULATION: The 3513 nulliparous participants of the SCOPE
      study. METHODS: Women were interviewed at 15 +/- 1 weeks, and had ultrasound
      growth measurements and umbilical and uterine Doppler studies at 20 +/- 1 weeks.
      Variables associated with SGA infants were identified using logistic regression.
      MAIN OUTCOME MEASURES: Small for gestational age (i.e. a birthweight of less than
      the tenth customised centile), normotensive-SGA and hypertensive-SGA. Comparison
      groups for statistical analyses were non-SGA, normotensive non-SGA and
      hypertensive non-SGA. RESULTS: Among 376 (10.7%) SGA infants, 281 (74.7%) were
      normotensive-SGA and 95 (25.3%) were hypertensive-SGA. Independent risk factors
      for normotensive-SGA were low maternal birthweight, low fruit intake pre
      pregnancy, cigarette smoking, increasing maternal age, daily vigorous exercise,
      being a tertiary student, head and abdominal circumference of less than the tenth
      centile and increasing uterine artery Doppler indices at the 20-week scan.
      Protective factors were: high green leafy vegetable intake pre-pregnancy, and
      rhesus-negative blood group. Risk factors for hypertensive-SGA were conception by
      in vitro fertilisation, previous early pregnancy loss and femur length of less
      than tenth centile at the 20-week scan. CONCLUSIONS: Risk factors for infants who
      are SGA by customised centiles have been identified in a cohort of healthy
      nulliparous women. A number of these factors are modifiable; however, further
      studies are needed to replicate these findings.

PMID- 21078056
TI  - Oxytocin to augment labour during home births: an exploratory study in the urban
      slums of Dhaka, Bangladesh.
AB  - OBJECTIVE: In Bangladesh, the majority of women give birth at home. There is
      anecdotal evidence that unqualified allopathic practitioners (UAPs) administer
      oxytocin at home births to augment labour pain. The objective is to explore the
      use of oxytocin to augment labour pain during home births in an urban slum in
      Dhaka, Bangladesh. DESIGN: Cross-sectional survey. SETTING: KamrangirChar slum,
      Dhaka, Bangladesh. POPULATION: Married women with a home birth or who experienced
      labour at home in the 6 months prior to the survey (n = 463) were interviewed.
      Twenty-seven UAPs were interviewed to validate women's responses. METHODS:
      Bivariate and multivariate logistic regressions were used to identify significant
      predictors of oxytocin use. MAIN OUTCOME MEASURES: Reported use of oxytocin to
      augment labour pain. RESULTS: Forty-six percent of women reported using medicine
      or other treatments to augment labour pain, 131 of whom reported using oxytocin
      (28% of total). Traditional birth attendants were the predominant decision-makers
      of when to use oxytocin. The medication was provided by a UAP who administered
      the drug via saline infusion or intramuscular injection. Higher education, lower
      parity, reported long labour (more than 12 hours), and knowledge of and positive
      attitudes towards oxytocin were significantly associated with oxytocin use after
      controlling for other factors. In the validation exercise, there was agreement
      about the use of oxytocin to augment labour in 22 of 27 cases (82%). CONCLUSIONS:
      About one-third of women used oxytocin to augment labour pain. This practice has
      implications for health education as well as future research to assess the impact
      on adverse maternal and neonatal outcomes.

PMID- 21078057
TI  - Cost-effectiveness of rapid tests and other existing strategies for screening and
      management of early-onset group B streptococcus during labour.
AB  - OBJECTIVE: To determine the cost-effectiveness of alternative screening and
      prevention strategies, including rapid intrapartum testing, for prevention of
      early-onset neonatal group B streptococcus (GBS) infection in the UK. DESIGN: A
      decision model was developed to investigate the cost-effectiveness of screening
      and prevention strategies for GBS. A strategy of doing nothing was also
      considered. Deterministic and probabilistic sensitivity analyses were carried
      out. SETTING: Two large UK based obstetric units. PARTICIPANTS: Test accuracy
      data were obtained from a primary study of rapid tests at the onset of labour and
      risk factors from 1400 women. MAIN OUTCOME MEASURES: Incremental health sector
      costs per case of early-onset GBS death avoided. RESULTS: Compared with a
      strategy of do nothing, the incremental cost-effectiveness ratio was L32,000 per
      Early-Onset GBS Disease avoided and L427,000 per Early-Onset GBS Death avoided
      for the strategy of providing routine intrapartum antibiotic prophylaxis to all
      women without prior screening; Based on their current sensitivity, specificity
      and cost, screening using rapid tests was dominated by other more cost-effective
      strategies. CONCLUSIONS: The most cost-effective strategy was shown to be the
      provision of routine intrapartum antibiotic prophylaxis to all women without
      prior screening but, given broader concerns relating to antibiotic use, this is
      unlikely to be acceptable. In its absence, intrapartum antibiotic prophylaxis
      directed by screening with enriched culture becomes cost-effective. The current
      strategy of risk-factor-based screening is not cost-effective compared with
      screening based on culture.

PMID- 21078058
TI  - A study of paediatric and adolescent gynaecology services in a British district
      general hospital.
AB  - OBJECTIVE: The Paediatric and Adolescent Gynaecology service (PAG) at Kettering
      General Hospital is a designated service meeting the needs of children with
      gynaecological problems. National guidelines reinforce the fact that children
      should be seen within specific paediatric areas in hospital. We aim to review the
      role of such a service in the context of a British district general hospital.
      DESIGN: Retrospective review spanning 15 years. SETTING: The outpatient/inpatient
      service of a UK district general hospital. POPULATION: A total of 800 patients
      were included in the study. METHODS: We identified patients attending the PAG
      clinic between 1994 and 2009. Medical notes were reviewed individually. MAIN
      OUTCOME MEASURES: Demographics, referral source, presenting symptoms, examination
      findings, diagnosis, management, admissions and referrals to tertiary centres.
      RESULTS: In total, 86% of patients were referred from primary care. The age
      distribution was bimodal at 4 and 15 years of age: the average age was 10 years.
      Sixty percent of patients were followed-up, giving a total of 2023 appointments.
      The commonest presentations were vulvovaginitis (18%), labial adhesions (14%),
      abdominal pain (7%) and precocious puberty (6%). A total of 15% of patients were
      admitted, largely for planned procedures, of which vaginoscopy was the most
      frequent. CONCLUSIONS: The PAG service has enabled pathways for care that were
      previously non-existent, as well as the development of 'best practice'. The
      British Society for Paediatric and Adolescent Gynaecology has been seeking to
      develop a network of similar services at secondary and tertiary level throughout
      the UK. This approach should be encouraged and promoted by those in charge of
      healthcare policy and provider trusts in general.

PMID- 21078059
TI  - The effects of uterine artery embolisation and surgical treatment on ovarian
      function in women with uterine fibroids.

PMID- 21078061
TI  - Cardiac arrest in pregnancy: increasing use of perimortem caesarean section due
      to emergency skills training?

PMID- 21078062
TI  - Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following
      caesarean section: the results of a double-blind randomised trial.

PMID- 21078064
TI  - Cerebrovascular pathophysiology following mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) or sport-induced concussion has recently
      become a prominent concern not only in the athletic setting (i.e. sports venue)
      but also in the general population. The majority of research to date has aimed at
      understanding the neurological and neuropsychological outcomes of injury as well
      as return-to-play guidelines. Remaining relatively unexamined has been the
      pathophysiological aspect of mTBI. Recent technological advances including
      transcranial Doppler ultrasound and near infrared spectroscopy have allowed
      researchers to examine the systemic effects of mTBI from rest to exercise, and
      during both asymptomatic and symptomatic conditions. In this review, we focus on
      the current research available from both human and experimental (animal) studies
      surrounding the pathophysiology of mTBI. First, the quest for a unified
      definition of mTBI, its historical development and implications for future
      research is discussed. Finally, the impact of mTBI on the control and regulation
      of cerebral blood flow, cerebrovascular reactivity, cerebral oxygenation and
      neuroautonomic cardiovascular regulation, all of which may be compromised with
      mTBI, is discussed.

PMID- 21078066
TI  - Arterial stiffness, but not endothelium-dependent vasodilation, is related to a
      low Ankle-Brachial index. The Prospective Investigation of the Vasculature in
      Uppsala Seniors (PIVUS).
AB  - BACKGROUND:   Arterial compliance and endothelium-dependent vasodilation are two
      characteristics of the vessel wall. In the Prospective Investigation of the
      Vasculature in Uppsala Seniors (PIVUS) study we studied the relationships between
      arterial compliance and endothelium-dependent vasodilation versus the Ankle
      Brachial index (ABI), a clinically used index of peripheral artery disease.
      METHODS:   In the population-based PIVUS study (all aged 70), arterial compliance
      was determined by ultrasound as the distensibility of the carotid artery and the
      stroke volume to pulse pressure (SV/PP) ratio by echocardiography, while
      endothelium-dependent vasodilation was assessed by the invasive forearm technique
      with acetylcholine (EDV) and brachial artery ultrasound (FMD) in 519 subjects in
      whom the Ankle-Brachial index was investigated. RESULTS:   After adjustments for
      gender and Framingham risk score, distensibility in the carotid artery and the
      SV/PP ratio were significantly reduced in subjects with a reduced ABI (< 0.9) in
      both legs (n=15, P = 0.0006 and P = 0.0003, respectively). Endothelium-dependent
      vasodilation was not significantly related to a reduced ABI. CONCLUSION:   A
      reduced arterial compliance, but not endothelium-dependent vasodilation, was
      related to a low ABI in both legs after adjustment for major risk factors,
      suggesting that atherosclerosis in the leg arteries is associated with arterial
      compliance also in other parts of the vasculature.

PMID- 21078065
TI  - Whole-body vibration alters blood flow velocity and neuromuscular activity in
      Friedreich's ataxia.
AB  - The purpose of this study was to investigate the effects of whole-body vibration
      (WBV) on blood flow velocity and muscular activity after different vibration
      protocols in Friedreich's ataxia (FA) patients. After two familiarization
      sessions ten patients received six 3 min WBV treatments depending on a
      combination of frequency (10, 20 or 30 Hz) and protocol (constant or fragmented).
      Femoral artery blood flow velocity, vastus lateralis (VL) and vastus medialis
      (VM) electromyography (EMG), and rate of perceived exertion were registered. Peak
      blood velocity was increased with respect to basal values after 1, 2 and 3 min of
      WBV (14.8%, 18.8% and 19.7%, respectively, P<0.001). Likewise, mean blood
      velocity was increased with respect to basal values after 1, 2 and 3 min of WBV
      (17.3%, 19.4% and 16.6%, respectively, P<0.001). EMG amplitude of VL and VM was
      increased (39% and 23%, respectively, P<0.05) and EMG frequencies decreased
      during the application of WBV. The results of this study suggest that higher
      frequencies (30 Hz) produce a greater increase in blood flow velocity and rate of
      perceived exertion. WBV is an effective method to increase blood flow and to
      activate muscle mass in patients with Friedreich's ataxia, and could therefore be
      considered to be incorporated in rehabilitation programs of this collective.

PMID- 21078067
TI  - A comparison of differential oscillometric device with invasive mean arterial
      blood pressure monitoring in intensive care patients.
AB  - Non-invasive beat-to-beat mean arterial pressure (MAP) in finger arteries
      recorded by the differential oscillometric device was compared with MAP recorded
      invasively from A. radialis in 22 patients after cardiac surgery. Based on all
      132 paired measurements, the MAP values measured at the radial artery were 2.7 +/
      4.9 mmHg higher than those measured on fingers. Among 22 patients there were 8
      patients receiving inotropic support, their difference being 2.1 +/- 5.6 mmHg.
      The present study revealed that the mean discrepancy between the invasive radial
      pressure and finger pressure was small; however, patient data sets showed marked
      variability in average pressure differences when examined individually.

PMID- 21078068
TI  - Subjects with sonographical hepatic steatosis should be excluded from studies to
      establish upper reference levels of serum transaminases.
AB  - BACKGROUND AND AIMS: Correct upper reference limits (URL) of serum liver enzyme
      activities are used to select individuals in whom further diagnostic procedures
      for suspected liver disorders are warranted and to compare the prevalence and
      incidence of increased serum liver enzyme levels within and among populations. We
      sought to establish URL in a general adult population by not only generating a
      disease-free population but also further excluding subjects with
      ultrasonographical diagnosis of hepatic steatosis. METHODS: We used data from
      4,242 subjects (2,154 women) aged 20-79 years recruited for the population-based
      Study of Health in Pomerania. A reference population was selected comprising
      1,953 subjects (1,129 women). Serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and gamma-glutamyltransferase (GGT) were measured
      photometrically. RESULTS: The exclusion of 630 subjects with hepatic steatosis
      and 20 subjects with equivocal data on liver ultrasound from the reference
      population predominantly affected the URL for serum ALT and GGT levels in younger
      age groups. URL for serum ALT, AST and GGT levels were 1.00 MUmol/L/s (60 U/L),
      0.55 MUmol/L/s (33 U/L) and 1.11 MUmol/L/s (67 U/L), respectively, in men as well
      as 0.57 MUmol/L/s (34 U/L), MUmol/L/s (25 U/L) and MUmol/L/s (39 U/L),
      respectively, in women. CONCLUSIONS: URL for serum liver enzyme activities are
      higher than recommended previously. Creating a reference population for
      establishing URL for serum liver enzyme activities should include liver
      ultrasound in order to exclude subjects with subclinical hepatic steatosis.

PMID- 21078070
TI  - Analysis of maxillofacial fracture victims in the Wenchuan earthquake and Yushu
      earthquake.
AB  - OBJECTIVE: To analyze retrospectively 419 patients after the Wenchuan earthquake
      and 46 after Yushu earthquake with maxillofacial fractures so as to provide
      reference on patients' treatment after an earthquake. METHOD: We investigated 419
      patients after Wenchuan earthquake and 46 after Yushu earthquake with
      maxillofacial fractures who were admitted to the West China Hospital of
      Stomatology and other 46 hospitals in 10 provinces. RESULT: A total of 58
      patients had maxillofacial fractures (13.8%) including 33 (56.9%) men and 25
      (43.1%) women after the Wenchuan earthquake and 6 (13%) had maxillofacial
      fractures after Yushu earthquake. Most patients were injured by pressing or
      burying. The nasal-orbital-ethmoidal region was the most frequent site of the
      maxillofacial fracture (58.6% in the Wenchuan earthquake and 66.7% in the Yushu
      earthquake). The most prevalent pattern of maxillofacial fracture was multiple
      and/or comminuted fractures (87.9% in the Wenchuan earthquake and 100% in the
      Yushu earthquake). There were 48 (82.8%) patients with associated injuries, and
      the most common site was extremity injuries (58.6%) after Wenchuan earthquake.
      Few patients received adequate prehospital treatment, with bandages
      predominantly. Most patients (65.5% in the Wenchuan earthquake and 100% in the
      Yushu earthquake) underwent open reduction and rigid internal fixation. We failed
      to find any patients with generalized infection. However, all patients in our
      study presented the symptoms of post-traumatic stress disorder. CONCLUSION: We
      analyze the characteristics of maxillofacial fractures after the two earthquakes,
      so as to improve our medical emergency system when such disasters happen again.

PMID- 21078071
TI  - Traumatic dental injuries during anaesthesia: part I: clinical evaluation.
AB  - Dental injuries represent the most common claims against the anaesthesiologist.
      Dental lesions are frequent complications of oro-tracheal intubation and major
      causal factors are (i) poor dentition, (ii) aggressive laryngoscopy, (iii)
      insufficient anaesthesia and curarization, (iv) emergency interventions and (v)
      lack of experience by the anaesthesiologist. MATERIALS AND METHODS: We conducted
      a retrospective analysis of 83 cases of dental lesions occurring during elective,
      emergent and urgent surgery requiring general anaesthesia with tracheal tube
      placement in the years between 2000 and 2008. Preoperative evaluation of dental
      status was obtained from the anaesthesiology chart, filled by an experienced
      anaesthesiologist during the preoperative visit. Anaesthesiological records were
      inspected by physicians of Legal Medicine Department with the aim to attribute
      responsibility for the damage and manage potential reimbursements. Costs related
      to the required dental repair were also noted. RESULTS: Eighty-three patients of
      a total of 60.000 surgical procedures (no day surgery) under general anaesthesia
      were affected by dental lesions (0.13%). Seventy-five per cent of lesions
      occurred during intubation manoeuvres for elective major surgery, 15% occurred at
      tracheal intubation for minor surgery and 10% were related to emergency surgery.
      Teeth avulsions accounted for 50% of lesions, followed by damage to crowns and
      bridges (14%), luxations and fractures (>15%). DISCUSSION: The overall incidence
      of dental injury in our retrospective study was 1.38 per 1000 anaesthetics, which
      is slightly higher than those reported by some and lower with respect to others.
      Avulsion of a permanent tooth occurred in patients who were affected by severe
      mobility of native teeth while undergoing surgery. Even though the majority of
      anaesthesiologists were trained enough in the use of airway devices and aware of
      the potential damage while using excessive forces, some unexpected difficulties
      may have led to lesions. It is known that damage to teeth can occur even in the
      absence of negligence.

PMID- 21078072
TI  - The effects of topical application of bisphosphonates on replanted rat molars.
AB  - The purpose of this study was to evaluate the potential usefulness of two
      bisphosphonates (BPs) (etidronate and zoledronate), compared with that of
      alendronate, which is a well-known drug for delayed replantation, in decreasing
      or preventing inflammatory root resorption and replacement root resorption in
      replanted teeth. Eighty-four Sprague Dawley rat maxillary first molars were
      extracted, dried for 60 min and then replanted after root treatment. The rats
      were divided into four groups (control, alendronate, etidronate, zoledronate) as
      following treatments of avulsed root before replantation. At 7, 14, and 28 days
      postreplantation, the animals were sacrificed and the samples obtained and
      process for microscopic analysis. The data were statistically analyzed with the
      SPSS procedure, anova test and each test was complemented by the Tukey's post hoc
      test. The result indicated that topical application of alendronate and
      zoledronate, both nitrogen containing BPs, prevented inflammatory root resorption
      and inflammatory cell response in the delayed replantation model. Both drugs were
      demonstrated similar effects in the delayed tooth replantation model (P = 0.9).
      Etidronate did not prevent inflammatory root resorption and inflammation in the
      delayed replantation (P < 0.05). No significant differences in replacement root
      resorption were observed among all drugs. These results suggest that when teeth
      are dried and not replanted immediately, zoledronate, like alendronate, may
      prevent root resorption and facilitates the regeneration of periodontal tissues
      after replantation.

PMID- 21078073
TI  - The consequences of orofacial trauma resulting from violence: a study in Porto.
AB  - Orofacial injuries resulting from violence are a fairly common event. In
      Portugal, however, the impact of these injuries remains to be elucidated. This
      study aims to analyze the injuries and permanent consequences of orofacial trauma
      (in a three-dimensional perspective: organic, functional and situational),
      resulting from violence. To do so, a retrospective analysis of all violence
      related forensic reports performed in the North Branch of the National Institute
      of Legal Medicine, during 2007, was carried out (n = 513). It was found that most
      victims were men with a mean age of 35.4 (SD = 15.1). Most aggressions were due
      to punches and/or kicks. The most frequent orofacial injuries were lip injuries
      (57.7%), followed by extra-oral soft tissue injuries (35.9%), gingival and oral
      mucosa injuries (29.2%), and teeth and/or periodontal injuries (17.5%). The most
      frequent long-term consequences concerned the teeth and periodontal area (14.0%),
      followed by the lip area (7.4%), and gingival and oral mucosa tissues (3.9%). In
      terms of the effect on functions and life situations, it was found that chewing
      and embarrassment in social life events were the most prevalent (43.6% and 83.6%,
      respectively). These results showed that orofacial trauma from violence-related
      events can damage a person's quality of life, especially those concerning the
      teeth area, as a result of their implications in normal function and in life
      situations.

PMID- 21078074
TI  - Effective treatment of self-injurious oral trauma in Lesch-Nyhan syndrome: a case
      report.
AB  - Lesch-Nyhan syndrome (LNS) is an X-linked disorder originating from deficiency of
      the enzyme hypoxanthine guanine phosphoribosyl transferase. It is characterized
      by neurological manifestations, including the dramatic symptom of compulsive self
      mutilation, which results in destruction of oral and perioral tissues. Several
      drug trials have been administered to improve the severe self-destructive
      behaviour, with questionable effectiveness. Invasive treatment approaches, such
      as extraction of teeth and orthognathic surgery, have been suggested with
      variable success. A conservative treatment with an intraoral appliance serving to
      prevent oral and peri-oral self-injury is presented in this report. The patient
      was a 14-year-old boy demonstrating the typical LNS behaviour, including
      compulsive self-biting, significant loss of lip and tongue tissue, spasticity and
      involuntary movements. An acrylic maxillary appliance was designed and
      constructed with an occlusal plate raising the bite. The appliance was retained
      by two Adams' clasps on the first premolars, along with three ball clasps between
      the incisors. Fabrication, insertion, and maintenance were uncomplicated and non
      stressful to the patient. Periodic recall over 3-year period has confirmed the
      effective healing of the oral lesions and a high level of tolerance of the
      appliance.

PMID- 21078075
TI  - Management of trauma-induced inflammatory root resorption using mineral trioxide
      aggregate obturation: two-year follow up.
AB  - Inflammatory root resorption is a serious complication of dental trauma, which
      leads to progressive loss of the root structure. This report describes the
      treatment a previously traumatized young maxillary lateral incisor, severely
      affected by inflammatory root resorption. An 11-year-old boy presented with pain
      and mobility in his maxillary incisors which experienced fall trauma 2 years
      earlier. Radiographic examination revealed incomplete root development of the
      right central incisor, associated with advanced inflammatory root resorption and
      a periapical lesion. Following removal of a prior long-term calcium hydroxide
      dressing, the root canal was submitted to a 2-week irrigation regimen involving
      1.25% sodium hypochlorite and 2% chlorhexidine gluconate. Thereafter, the entire
      root was filled with mineral trioxide aggregate. The radiographic follow up at 6
      months showed arrest of root resorption and initiation of periapical healing in
      the absence of clinical symptoms and mobility. This was followed by advanced
      osseous regeneration and re-establishment of the periodontal space at 12 and 24
      months. From the present case, it can be concluded that mineral trioxide
      aggregate obturation can be a viable option that can improve the healing outcomes
      in cases of severe inflammatory root resorption in young permanent teeth.

PMID- 21078076
TI  - Developmental dental alterations in permanent teeth after intrusion of the
      predecessors: clinical and microscopic evaluation.
AB  - This case report describes the management of developmental dental alterations in
      permanent dentition as a consequence of severe intrusive luxation in its
      predecessors in a child of 2 years. At 10 years of age, this patient was referred
      for consultation due to lack of permanent maxillary right central and lateral
      incisors. Radiographic examination revealed impaction of hypoplasic permanent
      maxillary central incisor, absence of the lateral incisor and compound odontoma
      in region of the permanent maxillary lateral incisor. The odontoma was surgically
      removed and unerupted central incisor was placed in orthodontic traction over a
      period of 8 months. The central incisor presented with abnormal shape and was
      restored with composite resin. Odontoma histologic analysis was carried out
      through Hematoxylin and Eosin coloration and Scanning Electron Microscopy. Cement
      and osteocement formations were found in soft tissue, as well as some irregularly
      distributed dentine islands of tooth-like structures, indicative of compound
      odontoma. We followed up this patient for 5 years and orthodontic management was
      successfully performed for correct alignment of the maxillary right central
      incisor impacted by compound odontoma.

PMID- 21078077
TI  - Comprehensive and sequential management of an impacted maxillary central incisor
      with severe crown-root dilacerations.
AB  - Tooth dilaceration refers to a dental anomaly characterized by an abrupt
      deviation in the longitudinal axis of tooth. Crown-root dilaceration is diagnosed
      in teeth with sharp angles at the cement-enamel junction. The greater the bending
      degree is, the less chance there is for successful teeth preservation and
      relocation. In this report, a clinical case of an impacted maxillary central
      incisor with severe crown-root dilacerations was described by means of an
      operative evaluation using three-dimensional dental computed tomography and a
      multidisciplinary approach that included surgical, orthodontic, endodontic,
      prosthetic and periodontal therapy.

PMID- 21078078
TI  - Management of root dilaceration of an impacted maxillary central incisor
      following orthodontic treatment: an unusual therapeutic outcome.
AB  - There are rare cases of impacted permanent central incisors with dilaceration, a
      dental deformity characterized by pronounced angulation of the longitudinal tooth
      axis. This paper presents the orthodontic alignment of a permanent maxillary left
      central incisor in a 7.5-year-old boy, which appeared impacted radiologically and
      displayed root dilaceration. Following surgical exposure with the closed-eruption
      technique and appropriate orthodontic traction, the tooth was successfully
      aligned into the dental arch and the root was radiologically shown to be
      straightened and relatively well developed.

PMID- 21078079
TI  - Arbitrary, contradictory and misleading methods and materials produces false
      results about the Save-A-Tooth emergency tooth preserving system.

PMID- 21078081
TI  - Dental health behaviours among early adolescents in Hong Kong.
AB  - OBJECTIVES: This study aimed to investigate the prevalence and socioeconomic
      differences in dental health behaviours among Hong Kong early adolescents.
      METHODS:  A cross-sectional survey was conducted among 4927 students (44.7% boys)
      aged 14-15 from 36 secondary schools in 2000-2001. Students reported their
      socioeconomic information and dental health behaviours using the Health Related
      Behaviour General Questionnaire (HRBGQ). Logistic regression models were used to
      determine the adjusted odds ratios of regular tooth brushing (at least twice
      daily), weekly use of dental floss (in the past 7days) and annual dental visit
      (in the past 12months) for different socioeconomic characteristics. RESULTS: Of
      the subjects, 77.8% reported to have brushed regularly, but only 22.3% used
      dental floss weekly and 37.9% had annual dental visit. Male gender and Chinese
      ethnicity were significantly associated with lower odds of regular brushing, use
      of dental floss and annual dental visit. Two or more siblings and not living with
      both parents were also significantly associated with lower odds of regular
      brushing and annual dental visit. Furthermore, students living in non-private
      housing were significantly less likely to have annual dental visit than those in
      private housing. CONCLUSIONS: Regular brushing was common, but not use of dental
      floss and annual dental visits among Hong Kong early adolescents. In general,
      socioeconomic disparity in dental health behaviours was observed. Extending the
      existing government-run dental health programmes to secondary school students in
      Hong Kong is warranted.

PMID- 21078082
TI  - Foot-and-mouth disease in Tanzania from 2001 to 2006.
AB  - Foot-and-mouth disease (FMD) is endemic in Tanzania, with outbreaks occurring
      almost each year in different parts of the country. There is now a strong
      political desire to control animal diseases as part of national poverty
      alleviation strategies. However, FMD control requires improving the current
      knowledge on the disease dynamics and factors related to FMD occurrence so
      control measures can be implemented more efficiently. The objectives of this
      study were to describe the FMD dynamics in Tanzania from 2001 to 2006 and
      investigate the spatiotemporal patterns of transmission. Extraction maps, the
      space-time K-function and space-time permutation models based on scan statistics
      were calculated for each year to evaluate the spatial distribution, the
      spatiotemporal interaction and the spatiotemporal clustering of FMD-affected
      villages. From 2001 to 2006, 878 FMD outbreaks were reported in 605 different
      villages of 5815 populated places included in the database. The spatial
      distribution of FMD outbreaks was concentrated along the Tanzania-Kenya, Tanzania
      Zambia borders, and the Kagera basin bordering Uganda, Rwanda and Tanzania. The
      spatiotemporal interaction among FMD-affected villages was statistically
      significant (P<=0.01) and 12 local spatiotemporal clusters were detected;
      however, the extent and intensity varied across the study period. Dividing the
      country in zones according to their epidemiological status will allow improving
      the control of FMD and delimiting potential FMD-free areas.

PMID- 21078083
TI  - The epidemiological characteristics of the 2007 foot-and-mouth disease epidemic
      in Sarpang and Zhemgang districts of Bhutan.
AB  - This study was undertaken to compare the epidemiological characteristics of the
      2007 foot-and-mouth disease outbreak in two districts of Sarpang and Zhemgang in
      Bhutan. Zhemgang district recorded a significantly higher cumulative incidence in
      all species (26.9%) as well as for cattle (29.3%) compared to Sarpang (6.5% and
      7.4%, respectively). The case fatality for cattle in Zhemgang (14.1%) was
      significantly higher than in Sarpang (3.3%). A total of 404 cattle and 73 pigs
      died of FMD in Zhemgang, whereas only 21 cattle died in Sarpang. Although all
      four species were affected in Sarpang, no sheep or goats were affected in
      Zhemgang. Spatiotemporal analyses showed the existence of four significant
      clusters, a primary one in Sarpang and three secondary clusters in Zhemgang. The
      virus belonged to the PanAsia strain of the Middle-East South-Asia topotype (O
      serotype), and the strain was closely related to the PanAsia strain that
      circulated in Bhutan during the 2003/2004 outbreaks. The severity of FMD
      infection in Zhemgang district could be attributed to low vaccination coverage
      (36.5% in 2006 when compared to 87.6% in Sarpang), inadequate biosecurity, poor
      nursing care of the sick animals and delayed reporting to the livestock centre.
      This study highlights the ability of the PanAsia strain of the O serotype to
      cause unprecedented morbidity and mortality, especially in a naive population.
      The study also highlights the benefits of maintaining good herd immunity in the
      susceptible population, through adequate vaccination coverage, to minimize the
      severity of infection and limit the spread of disease from infected to non
      infected herds.

PMID- 21078084
TI  - Interfering with interferon-gamma signalling in intestinal epithelial cells:
      selective inhibition of apoptosis-maintained secretion of anti-inflammatory
      interleukin-18 binding protein.
AB  - The intestinal epithelial barrier represents an important component in the
      pathogenesis of inflammatory bowel diseases. Interferon (IFN)-gamma, a T helper
      type 1 (Th1) cytokine, regulated by the interleukin (IL)-18/IL-18 binding protein
      (bp) system, modulates the integrity of this barrier. The aim of this work was to
      study functionally the consequences of IFN-gamma on intestinal epithelial cells
      (IEC) and to interfere selectively with identified adverse IFN-gamma effects. IEC
      lines were stimulated with IFN-gamma. IL-18 and IL-18bp were assessed by enzyme
      linked immunosorbent assay. Staining of phosphatidylserine, DNA laddering,
      lactate dehydrogenase (LDH) release, cleavage of poly-adenosine diphosphate
      ribose-polymerase (PARP) and activation of caspase-3 were analysed to determine
      cell death. Inhibitors of tyrosine kinase, caspase-3 or p38 mitogen-activated
      kinase ((MAP) activity were used. Cytokines were measured in supernatants of
      colonic biopsies of healthy controls and inflammatory bowel disease (IBD)
      patients. In IEC lines, IFN-gamma up-regulated IL-18bp selectively. Ex vivo, IFN
      gamma was present in supernatants from cultured biopsies and up-regulated with
      inflammation. Contrary to previous reports, IFN-gamma alone induced apoptosis in
      IEC lines, as demonstrated by phosphatidylserin staining, DNA cleavage and LDH
      release. Further, activation of caspase-3, PARP cleavage and expression of pro
      apoptotic Bad were induced. Partial inhibition of caspase-3 and of p38 but not
      JAK tyrosine kinase, preserved up-regulation of IL-18bp expression. Selective
      inhibition of IFN-gamma mediated apoptosis, while preserving its beneficial
      consequences on the ratio of IL-18/IL-18bp, could contribute to the integrity of
      the mucosal barrier in intestinal inflammation.

PMID- 21078085
TI  - Monoclonal antibodies to B and T lymphocyte attenuator (BTLA) have no effect on
      in vitro B cell proliferation and act to inhibit in vitro T cell proliferation
      when presented in a cis, but not trans, format relative to the activating
      stimulus.
AB  - B and T lymphocyte attenuator (BTLA) is an immunoglobulin superfamily member
      surface protein expressed on B and T cells. Its ligand, herpesvirus entry
      mediator (HVEM), is believed to act as a monomeric agonist that signals via the
      CRD1 of HVEM to inhibit lymphocyte activation: HVEM is also the receptor for
      lymphotoxin-alpha and LIGHT, which both bind in the CRD2 and CRD3 domains of the
      HVEM molecule, and for CD160 which competes with BTLA. We have shown that
      recombinant HVEM and a panel of different monoclonal antibodies specifically bind
      murine BTLA on both B and T cells and that some antibodies inhibit anti
      CD3epsilon-induced T cell proliferation in vitro, but only when constrained
      appropriately with a putatively cross-linking reagent. The antibodies had no
      significant effect on in vitro T cell proliferation in a mixed lymphocyte
      reaction (MLR) assay nor on in vitro DO11.10 antigen-induced T cell
      proliferation. None of these antibodies, nor HVEM-Fc, had any significant effect
      on in vitro B cell proliferation induced by anti-immunoglobulin M antibodies (+/
      anti-CD40) or lipopolysaccharide. We further elucidated the requirements for
      inhibition of in vitro T cell proliferation using a beads-based system to
      demonstrate that the antibodies that inhibited T cell proliferation in vitro were
      required to be presented to the T cell in a cis, and not trans, format relative
      to the anti-CD3epsilon stimulus. We also found that antibodies that inhibited T
      cell proliferation in vitro had no significant effect on the antibody captured
      interleukin-2 associated with the in vivo activation of DO11.10 T cells
      transferred to syngeneic recipient BALB/c mice. These data suggest that there may
      be specific structural requirements for the BTLA molecule to exert its effect on
      lymphocyte activation and proliferation.

PMID- 21078087
TI  - History and heroes: the thermal niche of fishes and long-term lake ice dynamics.
AB  - These perspectives on climate change come largely from two views, i.e. that of a
      fish and fisheries ecologist with an autecological interest and that of a
      limnologist interested in long-term dynamics and change. Ideas about the thermal
      niche evolved from the late F. E. J. Fry's (University of Toronto) paradigm of
      fish response to environmental factors and the late G. Evelyn Hutchinson's (Yale
      University) formalization of the niche concept. In contrast, ideas about climatic
      change and variability have been shaped by long-term observation records from
      lakes around the northern hemisphere. The history of each set of ideas, i.e. the
      thermal niche of fishes and learning from nature's long-term dynamics, is briefly
      reviewed in the context of climatic change.

PMID- 21078088
TI  - Climate change effects on fishes and fisheries: towards a cause-and-effect
      understanding.
AB  - Ongoing climate change is predicted to affect individual organisms during all
      life stages, thereby affecting populations of a species, communities and the
      functioning of ecosystems. These effects of climate change can be direct, through
      changing water temperatures and associated phenologies, the lengths and frequency
      of hypoxia events, through ongoing ocean acidification trends or through shifts
      in hydrodynamics and in sea level. In some cases, climate interactions with a
      species will also, or mostly, be indirect and mediated through direct effects on
      key prey species which change the composition and dynamic coupling of food webs.
      Thus, the implications of climate change for marine fish populations can be seen
      to result from phenomena at four interlinked levels of biological organization:
      (1) organismal-level physiological changes will occur in response to changing
      environmental variables such as temperature, dissolved oxygen and ocean carbon
      dioxide levels. An integrated view of relevant effects, adaptation processes and
      tolerance limits is provided by the concept of oxygen and capacity-limited
      thermal tolerance (OCLT). (2) Individual-level behavioural changes may occur such
      as the avoidance of unfavourable conditions and, if possible, movement into
      suitable areas. (3) Population-level changes may be observed via changes in the
      balance between rates of mortality, growth and reproduction. This includes
      changes in the retention or dispersion of early life stages by ocean currents,
      which lead to the establishment of new populations in new areas or abandonment of
      traditional habitats. (4) Ecosystem-level changes in productivity and food web
      interactions will result from differing physiological responses by organisms at
      different levels of the food web. The shifts in biogeography and warming-induced
      biodiversity will affect species productivity and may, thus, explain changes in
      fisheries economies. This paper tries to establish links between various levels
      of biological organization by means of addressing the effective physiological
      principles at the cellular, tissue and whole organism levels.

PMID- 21078086
TI  - The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients
      with inflammatory bowel disease: a concise review.
AB  - Patients with active inflammatory bowel disease (IBD) have elevated and activated
      myeloid leucocytes which infiltrate the colonic mucosa in vast numbers. Myeloid
      leucocytes such as the CD14(+) CD16(+) monocytes are major sources of tumour
      necrosis factor (TNF)-alpha, and therefore selective granulocyte/monocyte (GM)
      adsorption (GMA) should promote remission or enhance efficacy of pharmacological
      therapy. However, studies in IBD have reported both impressive as well as
      disappointing efficacy outcomes, indicating that patients' demographic factors
      might determine responders or non-responders to GMA. Nonetheless, this non-drug
      intervention has an excellent safety profile, and therapeutic GMA is expected to
      expand. In this review, attempts have been made to compile an update on the mode
      of actions (MoA) of the Adacolumn GMA. The MoA of GMA appears to be more than
      adsorption of excess neutrophils and TNF-producing CD14(+) CD16(+) monocytes per
      se. Adsorbed GMs release interleukin (IL)-1 receptor antagonist, hepatocyte
      growth factor and soluble TNF receptors, which are anti-inflammatory.
      Additionally, a sustained increase in lymphocytes including the regulatory CD4(+)
      CD25(+) T cells (lymphocyte sparing) is seen post-GMA. The impact of GMA on the
      immune system is potentially very interesting in the context of treating immune
      related diseases. Future studies are expected to add intriguing insights to the
      MoA of GMA.

PMID- 21078089
TI  - The influence of changing climate on the ecology and management of selected
      Laurentian Great Lakes fisheries.
AB  - The Laurentian Great Lakes Basin provides an ecological system to evaluate the
      potential effect of climate change on dynamics of fish populations and the
      management of their fisheries. This review describes the physical and biological
      mechanisms by which fish populations will be affected by changes in timing and
      duration of ice cover, precipitation events and temperature regimes associated
      with projected climate change in the Great Lakes Basin with a principal focus on
      the fish communities in shallower regions of the basin. Lake whitefish Coregonus
      clupeaformis, walleye Sander vitreus and smallmouth bass Micropterus dolomieu
      were examined to assess the potential effects of climate change on guilds of
      Great Lakes cold, cool and warm-water fishes, respectively. Overall, the
      projections for these fishes are for the increased thermally suitable habitat
      within the lakes, though in different regions than they currently inhabit. Colder
      water fishes will seek refuge further north and deeper in the water column and
      warmer-water fishes will fill the vacated habitat space in the warmer regions of
      the lakes. While these projections can be modified by a number of other habitat
      elements (e.g. anoxia, ice cover, dispersal ability and trophic productivity), it
      is clear that climate-change drivers will challenge the nature, flexibility and
      public perception of current fisheries management programmes. Fisheries agencies
      should develop decision support tools to provide a systematic method for
      incorporating ecological responses to climate change and moderating public
      interests to ensure a sustainable future for Great Lakes fishes and fisheries.

PMID- 21078090
TI  - Is there evidence for a shift in fish growth and recruitment success linked to
      climate change?
AB  - This study investigated whether a putative shift in climate regime in the North
      Atlantic in the 1990s coincided with changes in the growth and recruitment of
      roach Rutilus rutilus in the north-east of England. The relationships between R.
      rutilus growth and recruitment and the environment were significantly different
      before and after the putative shift in climate regime. Water temperature, river
      discharge, growth, recruitment success and the Gulf Stream Index co-varied until
      the late 1990s, indicating a gradual progression between periods of warm-and-dry
      and cold-and-wet summers. Since the late 1990s, there has been an increased
      prevalence of warm-and-wet summers, and recruitment success has oscillated
      between extremes on an almost annual basis. The north wall (northern boundary) of
      the Gulf Stream has been undergoing a displacement south since the late 1990s,
      and the speed and amplitude of the change appears to support the hypothesis that
      there was a regime shift in the climate of the North Atlantic Ocean. It is
      possible that a continued displacement south of the north wall of the Gulf Stream
      will lead to further increases in river discharge, reductions in water
      temperature and reduced fish growth and recruitment success in the long term.

PMID- 21078091
TI  - Temperature requirements of Atlantic salmon Salmo salar, brown trout Salmo trutta
      and Arctic charr Salvelinus alpinus: predicting the effects of climate change.
AB  - Atlantic salmon Salmo salar, brown trout Salmo trutta (including the anadromous
      form, sea trout) and Arctic charr Salvelinus alpinus (including anadromous fish)
      provide important commercial and sports fisheries in Western Europe. As water
      temperature increases as a result of climate change, quantitative information on
      the thermal requirements of these three species is essential so that potential
      problems can be anticipated by those responsible for the conservation and
      sustainable management of the fisheries and the maintenance of biodiversity in
      freshwater ecosystems. Part I compares the temperature limits for survival,
      feeding and growth. Salmo salar has the highest temperature tolerance, followed
      by S. trutta and finally S. alpinus. For all three species, the temperature
      tolerance for alevins is slightly lower than that for parr and smolts, and the
      eggs have the lowest tolerance; this being the most vulnerable life stage to any
      temperature increase, especially for eggs of S. alpinus in shallow water. There
      was little evidence to support local thermal adaptation, except in very cold
      rivers (mean annual temperature <6.5 degrees  C). Part II illustrates the
      importance of developing predictive models, using data from a long-term study
      (1967-2000) of a juvenile anadromous S. trutta population. Individual-based
      models predicted the emergence period for the fry. Mean values over 34 years
      revealed a large variation in the timing of emergence with c. 2 months between
      extreme values. The emergence time correlated significantly with the North
      Atlantic Oscillation Index, indicating that interannual variations in emergence
      were linked to more general changes in climate. Mean stream temperatures
      increased significantly in winter and spring at a rate of 0.37 degrees  C per
      decade, but not in summer and autumn, and led to an increase in the mean mass of
      pre-smolts. A growth model for S. trutta was validated by growth data from the
      long-term study and predicted growth under possible future conditions. Small
      increases (<2.5 degrees  C) in winter and spring would be beneficial for growth
      with 1 year-old smolts being more common. Water temperatures would have to
      increase by c. 4 degrees  C in winter and spring, and 3 degrees  C in summer and
      autumn before they had a marked negative effect on trout growth.

PMID- 21078092
TI  - Implications of climate change for the reproductive capacity and survival of New
      World silversides (family Atherinopsidae).
AB  - The New World silversides (family Atherinopsidae) are found in marine, estuarine
      and inland waters of North, Central and South America, where they are
      ecologically important as forage fishes and sometimes economically important for
      commercial and recreational fisheries. This report reviews the knowledge of the
      reproductive attributes of temperate and subtropical atherinopsids in relation to
      temperature and discusses the potential effects of climate change on their
      reproduction and adaptive responses. Their reproductive cycles are primarily
      entrained by photoperiod with high temperature acting as a limiting factor. They
      are generally multiple spawners which release successive batches of eggs in
      spring, but some species can spawn also in autumn and even summer when
      temperatures do not increase excessively. The decoupling of temperature patterns
      and photoperiod with further global warming and associated asymmetric thermal
      fluctuations could lead to spawning at times or temperatures that are unsuitable
      for larval development and growth. Many members of this family show temperature
      dependent sex determination (TSD), where the phenotypic sex of an individual is
      determined partly or wholly by the temperature experienced during gonadal sex
      differentiation, and high-temperature induced germ cell degeneration and
      decreased fertility. The predicted short-term reproductive responses of
      atherinopsids to climate change therefore include acceleration, shortening or
      overall disruption of spawning activity, and also more subtle, but nonetheless
      equally population-threatening, dysfunctions such as highly skewed sex ratios and
      partial or total loss of fertility. In the case of species with TSD, asymmetric
      thermal fluctuations could also cause larvae to encounter temperatures lower than
      normal during early development and be feminized. Such dysfunctions have been
      documented already in natural populations but are confined so far to landlocked,
      inland water habitats, perhaps because they impose more severe thermal
      fluctuations and limitations to migration and dispersal. The severity and
      recurrence of these dysfunctions with further climate change will depend both on
      the magnitude, speed and pattern of change and on how much (or how fast)
      physiological and behavioural traits can evolve to match the new conditions
      imposed by the climate, which is largely unknown. In this regard, compelling
      evidence is shown that numerous traits, including the sex determination system,
      are capable of rapid evolution and could mitigate the negative effects of
      temperature increases on population viability in atherinopsids.

PMID- 21078093
TI  - Interactions between riparian shading and food supply: a seasonal comparison of
      effects on time budgets, space use and growth in Atlantic salmon Salmo salar.
AB  - This study examines seasonal (winter v. summer) differences in space-time
      budgets, food intake and growth of Atlantic salmon Salmo salar parr in a
      controlled, large-scale stream environment, to examine the direction and
      magnitude of shifts in behaviour patterns as influenced by the availability of
      overhead cover and food supply. Salmo salar parr tested in the presence of
      overhead cover were significantly more nocturnal and occupied more peripheral
      positions than those tested in the absence of overhead cover. This increase in
      nocturnal activity was driven primarily by increased activity at night,
      accompanied by a reduction in daytime activity during winter. The presence of
      overhead cover had no effect on rates of food intake or growth for a given food
      supply in a given season. Growth rates were significantly higher for fish
      subjected to a high food supply than those subjected to a low food supply. Food
      supply did not affect the extent to which S. salar parr were nocturnal. These
      results were consistent between winter and summer. The use of riparian shading as
      a management technique to mitigate the effects of warming allows the adoption of
      more risk-averse foraging behaviour and may be particularly beneficial in
      circumstances where it serves also to increase the availability of food.

PMID- 21078094
TI  - The effect of elevated temperature on spawning of introduced pumpkinseed Lepomis
      gibbosus in Europe.
AB  - In an experimental comparison of pumpkinseed Lepomis gibbosus reproduction under
      ambient and climate change water temperature regimes, spawning occurred earlier
      in the season, which is likely to lead to greater young-of-the-year survival with
      concomitant implications in the U.K. under warmer climatic conditions.

PMID- 21078095
TI  - Vulnerability of pejerrey Odontesthes bonariensis populations to climate change
      in pampean lakes of Argentina.
AB  - The vulnerability of the pejerrey Odontesthes bonariensis population in Lake
      Chasico was assessed under different climate change conditions. During the
      sampling period, the water temperature was adequate for fish reproduction and to
      sustain an adequate sex ratio. Climate-driven higher temperatures, however, may
      severely distort population structure and cause drastic reduction or local
      extinction of stocks. Lake Chasico can be classified as eutrophic with clear
      waters and cyanobacteria that regularly cause fish mortality were identified as
      Nodularia spumigena and Oscillatoria sp. Global warming may strengthen the
      effects of eutrophication (e.g. toxic blooms or anoxia). Since many Cyanophyta
      species tolerate higher temperatures better than other algae, toxic blooms could
      increase. Furthermore, cyanobacteria have low nutritional value and could
      decouple the low-diversity food web. Lake Chasico has currently the salinity
      optimum (c. 20) for the development of the early life-history stages of O.
      bonariensis. Climate change, however, is likely to amplify the intensity of
      droughts or inundations. Floods can endanger O. bonariensis development due to
      its sub-optimal growth at low salinity and droughts could increase lake salinity
      and also temperature and nutrient concentration. In order to reduce some of the
      effects of climate change on the O. bonariensis population in Lake Chasico,
      integrated basin management based on an eco-hydrological approach is proposed.

PMID- 21078096
TI  - Predicted effects of climate warming on the distribution of 50 stream fishes in
      Wisconsin, USA.
AB  - Summer air and stream water temperatures are expected to rise in the state of
      Wisconsin, U.S.A., over the next 50 years. To assess potential climate warming
      effects on stream fishes, predictive models were developed for 50 common fish
      species using classification-tree analysis of 69 environmental variables in a
      geographic information system. Model accuracy was 56.0-93.5% in validation tests.
      Models were applied to all 86 898 km of stream in the state under four different
      climate scenarios: current conditions, limited climate warming (summer air
      temperatures increase 1 degrees  C and water 0.8 degrees  C), moderate warming
      (air 3 degrees  C and water 2.4 degrees  C) and major warming (air 5 degrees  C
      and water 4 degrees  C). With climate warming, 23 fishes were predicted to
      decline in distribution (three to extirpation under the major warming scenario),
      23 to increase and four to have no change. Overall, declining species lost
      substantially more stream length than increasing species gained. All three cold
      water and 16 cool-water fishes and four of 31 warm-water fishes were predicted to
      decline, four warm-water fishes to remain the same and 23 warm-water fishes to
      increase in distribution. Species changes were predicted to be most dramatic in
      small streams in northern Wisconsin that currently have cold to cool summer water
      temperatures and are dominated by cold-water and cool-water fishes, and least in
      larger and warmer streams and rivers in southern Wisconsin that are currently
      dominated by warm-water fishes. Results of this study suggest that even small
      increases in summer air and water temperatures owing to climate warming will have
      major effects on the distribution of stream fishes in Wisconsin.

PMID- 21078097
TI  - Cod Gadus morhua and climate change: processes, productivity and prediction.
AB  - Environmental factors act on individual fishes directly and indirectly. The
      direct effects on rates and behaviour can be studied experimentally and in the
      field, particularly with the advent of ever smarter tags for tracking fishes and
      their environment. Indirect effects due to changes in food, predators, parasites
      and diseases are much more difficult to estimate and predict. Climate can affect
      all life-history stages through direct and indirect processes and although the
      consequences in terms of growth, survival and reproductive output can be
      monitored, it is often difficult to determine the causes. Investigation of cod
      Gadus morhua populations across the whole North Atlantic Ocean has shown large
      scale patterns of change in productivity due to lower individual growth and
      condition, caused by large-scale climate forcing. If a population is being
      heavily exploited then a drop in productivity can push it into decline unless the
      level of fishing is reduced: the idea of a stable carrying capacity is a
      dangerous myth. Overexploitation can be avoided by keeping fishing mortality low
      and by monitoring and responding rapidly to changes in productivity. There are
      signs that this lesson has been learned and that G. morhua will continue to be a
      mainstay of the human diet.

PMID- 21078098
TI  - Climate change and the green energy paradox: the consequences for twaite shad
      Alosa fallax from the River Severn, U.K.
AB  - A stock-recruitment model with a temperature component was used to estimate the
      effect of an increase in temperature predicted by climate change projections on
      population persistence and distribution of twaite shad Alosa fallax. An increase
      of 1 and 2 degrees  C above the current mean summer (June to August) water
      temperature of 17.8 degrees  C was estimated to result in a three and six-fold
      increase in the population, respectively. Climate change is also predicted to
      result in an earlier commencement to their spawning migration into fresh water.
      The model was expanded to investigate the effect of any additional mortality that
      might arise from a tidal power barrage across the Severn Estuary. Turbine
      mortality was separated into two components: (1) juvenile (pre-maturation) on
      their out migration during their first year and on their first return to the
      river to spawn and (2) post-maturation mortality on adults on the repeat spawning
      component of the population. Under current conditions, decreasing pre-maturation
      and post-maturation survival by 8% is estimated to result in the stock becoming
      extinct. It is estimated that an increase in mean summer water temperature of 1
      degrees  C would mean that survival pre and post-maturation would need to be
      reduced by c. 10% before the stock becomes extinct. Therefore, climate change is
      likely to be beneficial to populations of A. fallax within U.K. rivers,
      increasing survival and thus, population persistence.

PMID- 21078099
TI  - Fish communities on the world's warmest reefs: what can they tell us about the
      effects of climate change in the future?
AB  - To examine the role of climatic extremes in structuring reef fish communities in
      the Arabian region, reef fish communities were visually surveyed at four sites
      within the southern Persian Gulf (also known as the Arabian Gulf and The Gulf),
      where sea-surface temperatures are extreme (range: 12-35 degrees  C annually),
      and these were compared with communities at four latitudinally similar sites in
      the biogeographically connected Gulf of Oman, where conditions are more moderate
      (range: 22-31 degrees  C annually). Although sites were relatively similar in the
      cover and composition of coral communities, substantial differences in the
      structure and composition of associated fish assemblages were apparent. Fish
      assemblages in the southern Persian Gulf held significantly lower estimates of
      abundance, richness and biomass, with significantly higher abundances of smaller
      sized individuals than Gulf of Oman assemblages. Functionally, southern Persian
      Gulf sites held significantly lower abundances of nearly all the common fish
      trophic guilds found on Gulf of Oman sites, although higher abundances of
      herbivorous grazers were apparent. These results suggest the potential for
      substantial changes in the structure of reef-associated fish communities,
      independent of changes in habitat within an environment of increasing
      fluctuations in oceanic climate.

PMID- 21078100
TI  - Using hierarchical models to estimate effects of ocean anomalies on north-west
      Pacific Chinook salmon Oncorhynchus tshawytscha recruitment.
AB  - The high variability in survival over the past three decades of north-west
      Pacific Chinook salmon Oncorhynchus tshawytscha is summarized for 24 stocks and
      analysed using hierarchical Bayesian models. Results from a simple model indicate
      that recruitment anomalies appear to be correlated in time and space. A simple
      model with a covariate based on basin-scale effects (Pacific Decadal Oscillation
      and El Nino Southern Oscillation) and local-scale effects (sea surface
      temperature, SST anomaly) was introduced to explain this variability. The model
      still exhibited residual patterns that were removed when a random-walk component
      was added to the model. The analysis indicates that recruitment is negatively
      related to SST anomaly for all stocks and the effect of basin-scale variables is
      negligible. The effect of climate over the next century is expected to result in
      estimated recruitment declining by an average of 13% for O. tshawytscha stocks
      coastwide.

PMID- 21078101
TI  - Socio-economic drivers of freshwater fish declines in a changing climate: a New
      Zealand perspective.
AB  - New Zealand has a freshwater fish fauna characterized by high levels of national
      and local endemism and which is threatened by anthropogenic stressors including
      habitat destruction or deterioration, commercial harvest, pollution and
      interactions with invasive exotic species. Significant expansion of New Zealand's
      dairy production has recently created further deterioration of lowland water
      quality and greater pressure for water allocation in drier eastern regions of the
      South Island. New Zealand has large freshwater resources and its climate is
      predicted to experience less dramatic changes in mean annual temperature and
      precipitation than many other regions of the world as a result of anthropogenic
      climate change. Predicted changes in regional climate and further expansion of
      the dairy industry, however, will impose similar pressures on freshwater
      resources in northern New Zealand to those already acting to threaten freshwater
      biodiversity in the eastern South Island.

PMID- 21078102
TI  - Climate change and oceanic barriers: genetic differentiation in Pomatomus
      saltatrix (Pisces: Pomatomidae) in the North Atlantic Ocean and the Mediterranean
      Sea.
AB  - Nucleotide variation of partial cytochrome b sequences was analysed in the
      bluefish Pomatomus saltatrix to investigate the population-structuring roles of
      climate change and oceanic barriers. Western and eastern North Atlantic Ocean
      populations appeared to be totally isolated, with the latter connected to the
      Mediterranean Sea within which further structuring occurred.

PMID- 21078103
TI  - Effects of different stimulus locations on inhibitory responses in human jaw
      closing muscles.
AB  - The aim of this study was to examine the inhibitory responses in bilateral
      masseter and temporalis muscle activity when electrical stimulation with short or
      long duration was applied to six oro-facial locations. The exteroceptive
      suppression period (ES2) and inhibitory responses were recorded in the surface
      electromyogram (EMG) of bilateral masseter and temporalis muscles in 16 healthy
      subjects. Two stimulus durations (1 ms single pulse and 450 ms pulse train)
      adjusted to a perceived intensity of 7 (distinct painful) on a 0-10 Numerical
      Rating Scale (NRS) were applied to the following six oro-facial locations on the
      right side while the subject was biting at 50% of the maximal voluntary
      contraction: masseter muscle, temporalis muscle, temporomandibular joint,
      infraorbital nerve, supraorbital nerve, and mental nerve. The stimulus intensity
      required to reach an NRS score of 7 was significantly lower for 450 ms train
      stimuli than for 1 ms single stimuli (P<0.001). There were no significant
      differences in the magnitude of ES2 suppression among the six different locations
      (P>0.876) for the 1 ms single stimuli. There were significant decreases in Root
      Mean-Square-EMG values in the 400-500 ms post-stimulus epoch compared with the
      pre-stimulus epoch (P<0.023) for 450 ms train stimuli, but there were no
      significant differences in the magnitude of inhibition among the six different
      locations (P<0.893). Short- and long-lasting electrical stimulation of various
      oro-facial locations induces similar bilateral inhibitory effects in the jaw
      closing muscles but with different propensity which may reflect the somatotopic
      organisation of these responses.

PMID- 21078104
TI  - ADULT syndrome caused by a mutation previously associated with EEC syndrome.
AB  - Acro-Dermato-Ungual-Lacrimal-Tooth (ADULT) syndrome is a rare autosomal dominant
      syndrome characterized by ectrodactyly or syndactyly, excessive freckling and dry
      skin, dysplastic nails, lacrimal duct atresia, primary hypodontia and early loss
      of permanent teeth. ADULT syndrome is one of five such syndromes that result from
      mutations in TP63, encoding the transcription factor p63. Until now, only four
      families and three individuals with ADULT syndrome have been reported in the
      English literature. We present a 14-year-old female patient with ADULT syndrome
      and discuss phenotype-genotype correlations in the p63 syndromes.

PMID- 21078105
TI  - Localized aquadynia responsive to clonidine in a 13-year-old girl.
AB  - A 13-year-old girl sought medical care for pain in both palms that consistently
      occurred after brief exposure to water and resolved spontaneously 20 to 30
      minutes after immersion. The pain was not associated with wrinkling of the palms.
      After excluding other causes of acrodynia and water-induced discomfort, we
      diagnosed the patient as having idiopathic localized aquadynia. Treatment with
      systemic clonidine led to a substantial improvement in her symptoms. To our
      knowledge, this patient represents the only fifth reported case of aquadynia and
      the first child affected by this enigmatic condition.

PMID- 21078106
TI  - Psychiatric symptoms and health-related quality of life in children and
      adolescents with psoriasis.
AB  - Information about the relationship between psoriasis and psychiatric morbidity
      and quality of life in children and adolescents is limited. We aimed to examine
      the symptoms of depression and anxiety and health-related quality of life levels
      in children and adolescents with psoriasis. Forty-eight outpatients with
      psoriasis aged 8 to 18 years are included in this study. Child Depression
      Inventory (CDI), State-Trait Anxiety Inventories for Children (STAI-C) and
      Pediatric Quality of Life Inventory Parent and Child Versions (PedQL-P and C)
      were applied to both patient and control groups. Psoriasis symptom severity was
      measured by the Psoriasis Area Severity Index (PASI). Both study and control
      groups were divided into two age groups, child (8-12 yrs) and adolescent (13-18
      yrs), to exclude the effect of puberty on psychological condition. The mean CDI
      score was higher, and PedQL-C psychosocial and total scores were lower in the
      children compared with controls. Duration of psoriasis had an increasing effect
      on physical-health and total scores of PedQL-C in the child group and all PedQL-C
      scores in the entire sample. Psoriasis severity showed a negative correlation
      with psychosocial and total scores of PedQL-P in the adolescent group and PedQL-P
      physical-health scores in the entire sample. Psoriasis is related to depression
      and impaired quality of life in children. The depressive symptoms in children
      with psoriasis should not be overlooked and psychiatric assessment of these
      children should be provided.

PMID- 21078107
TI  - The impact of childhood atopic dermatitis on the patients' family.
AB  - Atopic dermatitis is a common childhood disease that impairs quality of life. The
      study aimed to clarify the impact of childhood atopic dermatitis on family life
      and to correlate severity of atopic dermatitis with family life. A cross
      sectional survey was conducted at Qassim Region of Saudi Arabia over a period of
      4 months extending from April to July 2009. The parents of children with atopic
      dermatitis were asked through a validated "Dermatitis Family Impact
      Questionnaire" about the impact of the disease on their life. For each
      questionnaire, a total score of 0 to 5 is considered as normal quality of life, 6
      to 10 as low, 11 to 20 as moderate and >20 as high alteration in quality of life.
      The severity of the disease was evaluated using the SCORAD index. A total of 447
      children with atopic dermatitis were included in the study. Their mean age was
      65.9 months. Males constituted 57% of the patients. The mean score for quality of
      life in affected families was 13.9 (minimum 2, maximum 25). Based on our
      suggested classification, only 15 (3.4%) had normal quality of life, 104 (23.3%)
      were mildly affected, 297 (66.4%) were moderately affected, while 31 (6.9%)
      reported severe alternation in their quality of life. Sleep, monthly expenditure,
      and food preparation were the activities showing the highest level of
      disturbance. The disturbance in quality of life was significantly correlated to
      increasing severity of the disease. The study has emphasized the importance of
      investigating the quality of life of atopic dermatitis families. A simple
      questionnaire is a useful guide for appropriate management of the disease.

PMID- 21078108
TI  - Segmental vitiligo following encephalitis.
AB  - We describe a rare account of a patient who developed segmental vitiligo within
      several months of an episode of viral encephalitis. This case provides further
      support to the neuronal hypothesis in the etiology of segmental vitiligo. A
      literature review of the neuronal theory and pathogenesis of vitiligo is further
      discussed.

PMID- 21078109
TI  - Migrating hair: a case confused with cutaneous larva migrans.
AB  - Pili migrans is an unusual skin condition in which a hair shaft migrates under
      the surface of the skin and mimics the parasitic infection, cutaneous larva
      migrans. If the migrating hair is located on the sole of the foot, it represents
      a foreign body from an exogenous source. We present a 3-year-old boy with
      bilateral pili migrans on the soles of his feet, acquired after running around in
      his socks while at his mother's beauty salon. This case highlights a distinctive
      presentation of a foreign body penetration of the skin that can easily be
      confused for and should be differentiated from the parasitic disease, cutaneous
      larva migrans.

PMID- 21078110
TI  - An inflammatory reaction surrounding molluscum contagiosum as possible
      manifestation of immune reconstitution inflammatory syndrome in HIV infection.
AB  - Highly active antiretroviral therapy can restore specific immune responses and
      control of microorganism infections in human immunodeficiency virus-positive
      patients. This immune recovery may cause an inflammatory reaction to microbial
      and autoimmune antigens known as immune reconstitution inflammatory syndrome. We
      describe a clinical case with an intense inflammatory response surrounding
      molluscum contagiosum after highly active antiretroviral therapy. The clinical
      and laboratory findings suggested that the reaction was due to immune
      reconstitution inflammatory syndrome occurring during a period of immune recovery
      in a child with acquired immune deficiency syndrome.

PMID- 21078111
TI  - Primitive myxoid mesenchymal tumor of infancy in a preterm infant.
AB  - Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity
      that has been added to the differential diagnosis of myxoid tumors of the soft
      tissue. Few cases have been reported of this entity in the literature, but none
      presenting in a preterm infant. We present the case and clinical course of a
      preterm boy with a primitive myxoid mesenchymal tumor of infancy that occurred
      following excision of a congenital juvenile xanthogranuloma.

PMID- 21078112
TI  - Therapeutic molecular targets in human chondrosarcoma.
AB  - Chondrosarcomas are malignant cartilage tumours. They are poorly responsive to
      chemotherapy and radiotherapy. Treatment is usually limited to surgical
      resection; however, survival of patients with high-grade chondrosarcoma is poor,
      even with wide surgical resection. Induction of apoptosis in chondrosarcoma
      cells, either directly or by enhancement of the response to chemotherapeutic
      drugs and radiation, may be a route by which outcome can be improved. In this
      article, we review potential molecular targets that regulate chondrocyte
      apoptosis and discuss the experimental evidence for their utility.

PMID- 21078113
TI  - Some highlights of research on aging with invertebrates, 2010.
AB  - This annual review focuses on invertebrate model organisms, which continue to
      yield fundamental new insights into mechanisms of aging. This year, the budding
      yeast has been used to understand how asymmetrical partitioning of cellular
      constituents at cell division can produce a rejuvenated offspring from an aging
      parent. Blocking of sensation of carbon dioxide is shown to extend fly lifespan
      and to mediate the lifespan-shortening effect of sensory exposure to fermenting
      yeast. A new study of daf-16, the key forkhead transcription factor that mediates
      extension of lifespan by mutants in the insulin-signalling pathway in
      Caenorhabditis elegans, demonstrates that expression of tissue-specific isoforms
      with different patterns of response to upstream signalling mediates the highly
      pleiotropic effects of the pathway on lifespan and other traits. A new approach
      to manipulating mitochondrial activity in Drosophila, by introducing the yeast
      NADH-ubiquinone oxidoreductase, shows promise for understanding the role of
      mitochondrial reactive oxygen species in aging. An exciting new study of yeast
      and mammalian cells implicates deterioration of the nuclear pore, and consequent
      leakage of cytoplasmic components into the nucleus, as an important cause of
      aging in postmitotic tissues. Loss of, or damage to, chromosome-associated
      histones is also implicated in the determination of lifespan in yeast, worms and
      fruit flies. The relationship between functional aging, susceptibility to aging
      related disease and lifespan itself are explored in two studies in C. elegans,
      the first examining the role of dietary restriction and reduced insulin
      signalling in cognitive decline and the second profiling aggregation of the
      proteome during aging. The invertebrates continue to be a power house of
      discovery for future work in mammals.

PMID- 21078114
TI  - The tumor suppressor ING1 contributes to epigenetic control of cellular
      senescence.
AB  - Cellular senescence is an effective tumor-suppressive mechanism that causes a
      stable proliferative arrest in cells with potentially oncogenic alterations.
      Here, we have investigated the role of the p33ING1 tumor suppressor in the
      regulation of cellular senescence in human primary fibroblasts. We show that
      p33ING1 triggers a senescent phenotype in a p53-dependent fashion. Also,
      endogenous p33ING1 protein accumulates in chromatin in oncogene-senescent
      fibroblasts and its silencing by RNA interference impairs senescence triggered by
      oncogenes. Notably, the ability to induce senescence is lost in a mutant version
      of p33ING1 present in human tumors. Using specific point mutants, we further show
      that recognition of the chromatin mark H3K4me3 is essential for induction of
      senescence by p33ING1. Finally, we demonstrate that ING1-induced senescence is
      associated to a specific genetic signature with a strong representation of
      chemokine and cytokine signaling factors, which significantly overlaps with that
      of oncogene-induced senescence. In summary, our results identify ING1 as a
      critical epigenetic regulator of cellular senescence in human fibroblasts and
      highlight its role in control of gene expression in the context of this tumor
      protective response.

PMID- 21078115
TI  - Designing highly active siRNAs for therapeutic applications.
AB  - The discovery of RNA interference (RNAi) generated considerable interest in
      developing short interfering RNAs (siRNAs) for understanding basic biology and as
      the active agents in a new variety of therapeutics. Early studies showed that
      selecting an active siRNA was not as straightforward as simply picking a sequence
      on the target mRNA and synthesizing the siRNA complementary to that sequence. As
      interest in applying RNAi has increased, the methods for identifying active siRNA
      sequences have evolved from focusing on the simplicity of synthesis and
      purification, to identifying preferred target sequences and secondary structures,
      to predicting the thermodynamic stability of the siRNA. As more specific details
      of the RNAi mechanism have been defined, these have been incorporated into more
      complex siRNA selection algorithms, increasing the reliability of selecting
      active siRNAs against a single target. Ultimately, design of the best siRNA
      therapeutics will require design of the siRNA itself, in addition to design of
      the vehicle and other components necessary for it to function in vivo. In this
      minireview, we summarize the evolution of siRNA selection techniques with a
      particular focus on one issue of current importance to the field, how best to
      identify those siRNA sequences likely to have high activity. Approaches to
      designing active siRNAs through chemical and structural modifications will also
      be highlighted. As the understanding of how to control the activity and
      specificity of siRNAs improves, the potential utility of siRNAs as human
      therapeutics will concomitantly grow.

PMID- 21078116
TI  - Efficient and targeted delivery of siRNA in vivo.
AB  - RNA interference (RNAi) has been regarded as a revolutionary tool for
      manipulating target biological processes as well as an emerging and promising
      therapeutic strategy. In contrast to the tangible and obvious effectiveness of
      RNAi in vitro, silencing target gene expression in vivo using small interfering
      RNA (siRNA) has been a very challenging task due to multiscale barriers,
      including rapid excretion, low stability in blood serum, nonspecific accumulation
      in tissues, poor cellular uptake and inefficient intracellular release. This
      minireview introduces major challenges in achieving efficient siRNA delivery in
      vivo and discusses recent advances in overcoming them using chemically modified
      siRNA, viral siRNA vectors and nonviral siRNA carriers. Enhanced specificity and
      efficiency of RNAi in vivo via selective accumulations in desired tissues,
      specific binding to target cells and facilitated intracellular trafficking are
      also commonly attempted utilizing targeting moieties, cell-penetrating peptides,
      fusogenic peptides and stimuli-responsive polymers. Overall, the crucial roles of
      the interdisciplinary approaches to optimizing RNAi in vivo, by efficiently and
      specifically delivering siRNA to target tissues and cells, are highlighted.

PMID- 21078117
TI  - Staying on message: design principles for controlling nonspecific responses to
      siRNA.
AB  - Short interfering RNAs (siRNA) are routinely used in the laboratory to induce
      targeted gene silencing by RNA interference, and increasingly, this technology is
      being translated to the clinic. However, there are multiple mechanisms by which
      siRNA may be recognized by receptors of the innate immune system, including both
      endosomal Toll-like receptors and cytoplasmic receptors. Signaling through these
      receptors may induce multiple nonspecific effects, including general reductions
      in gene expression and the production of type I interferons and inflammatory
      cytokines, which can lead to systemic inflammation in vivo. The pattern of immune
      activation varies depending upon the types of cells and receptors that are
      stimulated by a particular siRNA. Although we are still discovering the
      mechanisms by which these recognition events occur, our current understanding
      provides useful guidelines for avoiding immune activation. In this minireview, we
      present a design-based approach for developing siRNA-based experiments and
      therapies that evade innate immune recognition and control nonspecific effects.
      We describe strategies and trade-offs related to siRNA design considerations
      including the choice of siRNA target sequence, chemical modifications to the RNA
      backbone and the influence of the delivery method on immune activation. Finally,
      we provide suggestions for conducting appropriate controls for siRNA experiments,
      because some commonly employed strategies do not adequately account for known
      nonspecific effects and can lead to misinterpretation of the data. By
      incorporating these principles into siRNA design, it is generally possible to
      control nonspecific effects, and doing so will help to best utilize this powerful
      technology for both basic science and therapeutics.

PMID- 21078120
TI  - FH8--a small EF-hand protein from Fasciola hepatica.
AB  - Vaccine and drug development for fasciolasis rely on a thorough understanding of
      the mechanisms involved in parasite-host interactions. FH8 is an 8 kDa protein
      secreted by the parasite Fasciola hepatica in the early stages of infection.
      Sequence analysis revealed that FH8 has two EF-hand Ca(2+)-binding motifs, and
      our experimental data show that the protein binds Ca(2+) and that this induces
      conformational alterations, thus causing it to behave like a sensor protein.
      Moreover, FH8 displays low affinity for Ca(2+) (K(obs) = 10(4) m(-1)) and is
      highly stable in its apo and Ca(2+)-loaded states. Homology models were built for
      FH8 in both states. It has only one globular domain, with two binding sites and
      appropriate groups in the positions for coordination of the metal ions. However,
      an unusually high content of positively charged amino acids in one of the binding
      sites, when compared with the prototypical sensor proteins, potentially affects
      the protein's affinity for Ca(2+). The only Cys present in FH8, conserved in the
      homologous proteins of other helminth parasites, is located on the surface,
      allowing the formation of dimers, detected on SDS gels. These findings reflect
      specificities of FH8, which are most probably related to its roles both in the
      parasite and in the host.

PMID- 21078119
TI  - Neural retina leucine-zipper regulates the expression of Ppp2r5c, the regulatory
      subunit of protein phosphatase 2A, in photoreceptor development.
AB  - Protein phosphatase 2A plays an important role in balancing phosphorylation
      signals that are critical for cell proliferation and differentiation. Here, we
      report that Ppp2r5c (regulatory subunit of protein phosphatase 2A) expression was
      regulated by the transcription factor neural retina leucine-zipper (Nrl) through
      enhancement of its transcriptional activity on the Ppp2r5c promoter. Using
      electrophoretic mobility shift assays and chromatin immunoprecipitation, we also
      found that Nrl bound directly to the Nrl-response element on the Ppp2r5c
      promoter. The affinity of binding of Nrl to the Ppp2r5c promoter was tightly
      regulated during mouse photoreceptor development. Overall, these results suggest
      that Ppp2r5c expression is regulated by Nrl during retinogenesis through direct
      binding to the promoter region of Ppp2r5c.

PMID- 21078118
TI  - Ca2+/calmodulin-stimulated PDE1 regulates the beta-catenin/TCF signaling through
      PP2A B56 gamma subunit in proliferating vascular smooth muscle cells.
AB  - The phenotypic change of vascular smooth muscle cells (VSMCs), from a
      'contractile' phenotype to a 'synthetic' phenotype, is crucial for pathogenic
      vascular remodeling in vascular diseases such as atherosclerosis and restenosis.
      Ca(2+)/calmodulin-stimulated phosphodiesterase 1 (PDE1) isozymes, including PDE1A
      and PDE1C, play integral roles in regulating the proliferation of synthetic
      VSMCs. However, the underlying molecular mechanism(s) remain unknown. In this
      study, we explore the role and mechanism of PDE1 isoforms in regulating beta
      catenin/T-cell factor (TCF) signaling in VSMCs, a pathway important for vascular
      remodeling through promoting VSMC growth and survival. We found that inhibition
      of PDE1 activity markedly attenuated beta-catenin/TCF signaling by downregulating
      beta-catenin protein. The effect of PDE1 inhibition on beta-catenin protein
      reduction is exerted via promoting glycogen synthase kinase 3 (GSK3)beta
      activation, beta-catenin phosphorylation and subsequent beta-catenin protein
      degradation. Moreover, PDE1 inhibition specifically upregulated phosphatase
      protein phosphatase 2A (PP2A) B56gamma subunit gene expression, which is
      responsible for the effects of PDE1 inhibition on GSK3beta and beta-catenin/TCF
      signaling. Furthermore, the effect of PDE1 inhibition on beta-catenin was
      specifically mediated by PDE1A but not PDE1C isozyme. Interestingly, in synthetic
      VSMCs, PP2A B56gamma, phospho-GSK3beta and phospho-beta-catenin were all found in
      the nucleus, suggesting that PDE1A regulates nuclear beta-catenin protein
      stability through the nuclear PP2A-GSK3beta-beta-catenin signaling axis. Taken
      together, these findings provide direct evidence for the first time that PP2A
      B56gamma is a critical mediator for PDE1A in the regulation of beta-catenin
      signaling in proliferating VSMCs.

PMID- 21078121
TI  - Cadmium-glutathione solution structures provide new insights into heavy metal
      detoxification.
AB  - Cadmium is a heavy metal and a pollutant that can be found in large quantities in
      the environment from industrial waste. Its toxicity for living organisms could
      arise from its ability to alter thiol-containing cellular components. Glutathione
      is an abundant tripeptide (gamma-Glu-Cys-Gly) that is described as the first line
      of defence against cadmium in many cell types. NMR experiments for structure and
      dynamics determination, molecular simulations, competition reactions for metal
      chelation by different metabolites (gamma-Glu-Cys-Gly, alpha-Glu-Cys-Gly and
      gamma-Glu-Cys) combined with biochemical and genetics experiments have been
      performed to propose a full description of bio-inorganic reactions occurring in
      the early steps of cadmium detoxification processes. Our results give unambiguous
      information about the spontaneous formation, under physiological conditions, of
      the Cd(GS)(2) complex, about the nature of ligands involved in cadmium chelation
      by glutathione, and provide insights on the structures of Cd(GS)(2) complexes in
      solution at different pH. We also show that gamma-Glu-Cys, the precursor of
      glutathione, forms a stable complex with cadmium, but biological studies of the
      first steps of cadmium detoxification reveal that this complex does not seem to
      be relevant for this purpose.

PMID- 21078122
TI  - A region within the C-terminal domain of Ure2p is shown to interact with the
      molecular chaperone Ssa1p by the use of cross-linkers and mass spectrometry.
AB  - The propagation of yeast prion phenotypes is highly dependent on molecular
      chaperones. We previously demonstrated that the molecular chaperone Ssa1p
      sequesters Ure2p in high molecular weight, assembly incompetent oligomeric
      species. We also determined the affinity of Ssa1p for Ure2p, and its globular
      domain. To map the Ure2p-Ssa1p interface, we have used chemical cross-linkers and
      MS. We demonstrate that Ure2p and Ssa1p form a 1 : 1 complex. An analytical
      strategy combining in-gel digestion of cross-linked protein complexes, and both
      MS and MS/MS analysis of proteolytic peptides, allowed us to identify a number of
      peptides that were modified because they are exposed to the solvent. A difference
      in the exposure to the solvent of a single lysine residue, lysine 339 of Ure2p,
      was detected upon Ure2p-Ssa1p complex formation. These observations strongly
      suggest that lysine 339 and its flanking amino acid stretches are involved in the
      interaction between Ure2p and Ssa1p. They also reveal that the Ure2p amino-acid
      stretch spanning residues 327-339 plays a central role in the assembly into
      fibrils.

PMID- 21078123
TI  - Crystal structure of UDP-galactose 4-epimerase-like L-threonine dehydrogenase
      belonging to the intermediate short-chain dehydrogenase-reductase superfamily.
AB  - The crystal structure of a L-threonine dehydrogenase (L-ThrDH; EC 1.1.1.103) from
      the psychrophilic bacterium Flavobacterium frigidimaris KUC-1, which shows no
      sequence similarity to conventional L-ThrDHs, was determined in the presence of
      NAD and a substrate analog, glycerol. The asymmetric unit consisted of two
      subunits related by a two-fold rotation axis. Each monomer consisted of a
      Rossmann-fold domain and a carboxyl-terminal catalytic domain. The overall fold
      of F. frigidimaris L-ThrDH showed significant similarity to that of UDP-galactose
      4-epimerase (GalE); however, structural comparison of the enzyme with E. coli and
      human GalEs showed clear topological differences in three loops (loop 1, loop 2
      and the NAD-binding loop) around the substrate and NAD binding sites. In F.
      frigidimaris L-ThrDH, loops 1 and 2 insert toward the active site cavity,
      creating a barrier preventing the binding of UDP-glucose. Alternatively, loop 1
      contributes to a unique substrate binding pocket in the F. frigidimaris enzyme.
      The NAD binding loop, which tightly holds the adenine ribose moiety of NAD in the
      Escherichia coli and human GalEs, is absent in F. frigidimaris L-ThrDH.
      Consequently, the cofactor binds to F. frigidimaris L-ThrDH in a reversible
      manner, unlike its binding to GalE. The substrate binding model suggests that the
      reaction proceeds through abstraction of the beta-hydroxyl hydrogen of L
      threonine via either a proton shuttle mechanism driven by Tyr143 and facilitated
      by Ser118 or direct proton transfer driven by Tyr143. The present structure
      provides a clear bench mark for distinguishing GalE-like L-ThrDHs from GalEs.

PMID- 21078124
TI  - GRAIL: a unique mediator of CD4 T-lymphocyte unresponsiveness.
AB  - GRAIL (gene related to anergy in lymphocytes, also known as RNF128), an ubiquitin
      protein ligase (E3), utilizes a unique single transmembrane protein with a split
      function motif, and is an important gatekeeper of T-cell unresponsiveness.
      Although it may play a role in other CD4 T-cell functions including activation,
      survival and differentiation, GRAIL is most well characterized as a negative
      regulator of T-cell receptor responsiveness and cytokine production. Here, we
      review the recent literature on this remarkable E3 in the regulation of human and
      mouse CD4 T-cell unresponsiveness.

PMID- 21078125
TI  - Plant RMR proteins: unique vacuolar sorting receptors that couple ligand sorting
      with membrane internalization.
AB  - In receptor-mediated sorting of soluble protein ligands in the endomembrane
      system of eukaryotic cells, three completely different receptor proteins for
      mammalian (mannose 6-phosphate receptor), yeast (Vps10p) and plant cells
      (vacuolar sorting receptor; VSR) have in common the features of pH-dependent
      ligand binding and receptor recycling. In striking contrast, the plant receptor
      homology-transmembrane-RING-H2 (RMR) proteins serve as sorting receptors to a
      separate type of vacuole, the protein storage vacuole, but do not recycle, and
      their trafficking pathway results in their internalization into the destination
      vacuole. Even though plant RMR proteins share high sequence similarity with the
      best-characterized mammalian PA-TM-RING family proteins, these two families of
      proteins appear to play distinctly different roles in plant and animal cells.
      Thus, this minireview focuses on this unique sorting mechanism and traffic of RMR
      proteins via dense vesicles in various plant cell types.

PMID- 21078126
TI  - Trafficking and proteolytic processing of RNF13, a model PA-TM-RING family
      endosomal membrane ubiquitin ligase.
AB  - RING finger protein 13 (RNF13) is a ubiquitously expressed, highly regulated
      ubiquitin ligase anchored in endosome membranes. A RING domain located in the
      cytoplasmic half of this type 1 membrane protein mediates ubiquitination in vitro
      but physiological substrates have not yet been identified. The protein localized
      in endosomal membranes undergoes extensive proteolysis in a proteasome-dependent
      manner, but the mRNA level can be increased and the encoded protein stabilized
      under specific physiological conditions. The cytoplasmic half of RNF13 is
      released from the membrane by regulatory proteases and therefore has the
      potential to mediate ubiquitination at distant sites independent of the full
      length protein. In response to protein kinase C activation, the full-length
      protein is stabilized and moves to recycling endosomes and to the inner nuclear
      membrane, which exposes the RING domain to the nucleoplasm. Thus RNF13 is a
      ubiquitin ligase that can potentially mediate ubiquitination in endosomes, on the
      plasma membrane, in the cytoplasm, in the nucleoplasm or on the inner nuclear
      membrane, with the site(s) regulated by signaling events that modulate protein
      targeting and proteolysis.

PMID- 21078127
TI  - RNF13: an emerging RING finger ubiquitin ligase important in cell proliferation.
AB  - Protein ubiquitination mediated by ubiquitin ligases plays a very important role
      in a wide spectrum of biological processes including development and disease
      pathogenesis. RING finger protein 13 (RNF13) is a recently identified ubiquitin
      ligase which contains an N-terminal protease-associated domain and a C-terminal
      RING finger domain separated by a transmembrane region. RNF13 is an
      evolutionarily conserved protein. Most interestingly, RNF13 expression is
      developmentally regulated during myogenesis and is upregulated in various human
      tumors. These data suggest that RNF13, acting as an ubiquitin ligase, might have
      profound biological functions during development and disease. This minireview
      summarizes recent work on RNF13 functions related to cell proliferation,
      differentiation and cancer development.

PMID- 21078128
TI  - Refined solution structure and backbone dynamics of the archaeal MC1 protein.
AB  - The 3D structure of methanogen chromosomal protein 1 (MC1), determined with
      heteronuclear NMR methods, agrees with its function in terms of the shape and
      nature of the binding surface, whereas the 3D structure determined with
      homonuclear NMR does not. The structure features five loops, which show a large
      distribution in the ensemble of 3D structures. Evidence for the fact that this
      distribution signifies internal mobility on the nanosecond time scale was
      provided by using (15)N-relaxation and molecular dynamics simulations. Structural
      variations of the arm (11 residues) induced large shape anisotropy variations on
      the nanosecond time scale that ruled out the use of the model-free formalism to
      analyze the relaxation data. The backbone dynamics analysis of MC1 was achieved
      by comparison with 20 ns molecular dynamics trajectories. Two beta-bulges showed
      that hydrogen bond formation correlated with phi and psi dihedral angle
      transitions. These jumps were observed on the nanosecond time scale, in agreement
      with a large decrease in (15)N-NOE for Gly17 and Ile89. One water molecule
      bridging NH(Glu87) and CO(Val57) through hydrogen bonding contributed to these
      dynamics. Nanosecond slow motions observed in loops LP3 (35-42) and LP5 (67-77)
      reflected the lack of stable hydrogen bonds, whereas the other loops, LP1 (10
      14), LP2 (22-24), and LP4 (50-53), were stabilized by several hydrogen bonds.
      Dynamics are often directly related to function. Our data strongly suggest that
      residues belonging to the flexible regions of MC1 could be involved in the
      interaction with DNA.

PMID- 21078129
TI  - Strong cytotoxic effect of the bradykinin antagonist BKM-570 in ovarian cancer
      cells--analysis of the molecular mechanisms of its antiproliferative action.
AB  - The standard chemotherapy for epithelial ovarian cancer (EOC) patients is
      currently a combination of taxane and platinum. However, most EOC patients still
      suffer relapses, and there is an immediate need for the development of novel and
      more effective therapeutic modalities against this deadly disease. Recently, the
      nonpeptide bradykinin (BK) antagonist 2,3,4,5,6-pentafluorocinnamoyl-(o-2,6
      dichlorobenzyl)-l-tyrosine-N-(4-amino-2,2,6,6-tetramethyl-piperidyl) amide (BKM
      570) was shown to cause impressive growth inhibition of lung and prostate tumors,
      displaying superior in vivo inhibitory effects than convential chemotherapeutic
      drugs. Here, we investigated BKM-570 cytotoxic effects in two EOC cell lines,
      derived from different EOC histopathologies: a clear cell carcinoma (TOV-21), and
      an endometrioid carcinoma (TOV-112). We showed that BKM-570 effectively inhibited
      the growth of ovarian cancer cells, as its cytotoxic effects were comparable to
      those of cisplatin, and were independent of the functional status of BK
      receptors. Moreover, BKM-570 synergized with cisplatin in inhibiting EOC cell
      growth. To better understand the molecular mechanisms of the antiproliferative
      action of this BK antagonist in EOC cells, we performed gene expression profiling
      in TOV-21 and TOV-112 cells following treatment with 10 MUM BKM-570 for 24 h. BKM
      570 displayed similar cytotoxic effects in the two cell lines analyzed, as genes
      with previously shown involvement in apoptosis/antiapoptosis and cell adhesion
      were proportionally upregulated and downregulated in both cell lines, whereas
      genes involved in basic cellular mechanisms, including cell growth and
      maintenance, metabolism, cell cycle control, inflammatory and immune response,
      signal transduction, protein biosynthesis, transcription regulation, and
      transport, were predominantly downregulated upon treatment. Our data are
      indicative of the therapeutic potential of BKM-570 and related compounds in EOC
      management.

PMID- 21078130
TI  - Cushing's syndrome and chronic venous ulceration--a clinical challenge.
AB  - Cushing's syndrome is a condition caused by high levels of glucocorticoids, or
      most commonly as a result of prolonged exposure to exogenous steroids. Clinical
      features include diabetes, hypertension, obesity, skin atrophy, immune
      suppression and delayed wound healing. We report a patient with iatrogenic
      Cushing's syndrome, in whom long-term topical steroid therapy was used to treat
      varicose eczema, which contributed to the development of type 2 diabetes, morbid
      obesity, sleep apnoea and chronic wound sepsis. In this case, repeated hospital
      admissions and systemic antibiotics were associated with considerable
      comorbidity. Aggressive local treatment, consisting of potassium permanganate
      soaks and irrigating gels, was highly effective in reducing the amount of
      exudate, pain and preventing from further deterioration of the patient's legs.

PMID- 21078131
TI  - Assessing bacterial burden in wounds: comparing clinical observation and wound
      swabs.
AB  - A randomised controlled trial (RCT) was conducted to compare the efficacy of
      nanocrystalline silver and cadexomer iodine dressings in healing chronic lower
      leg ulcers. The relationships between wound swab culture results and nurses'
      clinical assessments of critical colonisation, and between bacterial burden and
      healing rate, were also examined. There were 281 individuals with leg ulcers
      recruited. The bacterial burden of wounds was assessed using semi-quantitative
      wound swabs collected at baseline and intervals during the study. The study found
      no relationship between the nurses' clinical assessments and bacterial burden as
      identified from wound swabs in the wounds. A significant difference in wound
      healing was found with the use of nanocrystalline silver as compared to cadexomer
      iodine in the first 2 weeks of treatment when nil or low levels of leukocytes,
      gram positive bacilli, gram positive cocci or gram negative cocci were reported.
      This study has raised a number of questions regarding the need for further
      investigation into methods of assessing wound bacterial burden as well as the
      impact of wound biofilms on wound assessment and treatment.

PMID- 21078132
TI  - Regenerating matrix-based therapy for chronic wound healing: a prospective within
      subject pilot study.
AB  - The aim of this study was to determine whether a skin-specific bioengineered
      regenerating agent (RGTA) heparan sulphate mimetic (CACIPLIQ20) improves chronic
      wound healing. The design of this article is a prospective within-subject study.
      The setting was an urban hospital. Patients were 16 African-American individuals
      (mean age 42 years) with 22 wounds (mean duration 2.5 years) because of either
      pressure, diabetic, vascular or burn wounds. Two participants each were lost to
      follow-up or removed because of poor compliance, resulting in 18 wounds analysed.
      Sterile gauze was soaked with CACIPLIQ20 saline solution, placed on the wound for
      5 min, then removed twice weekly for 4 weeks. Wounds were otherwise treated
      according to the standard of care. Twenty-two percent of wounds fully healed
      during the treatment period. Wounds showed a 15.2-18.1% decrease in wound size as
      measured by the vision engineering research group (VERG) digital wound
      measurement system and total PUSH scores, respectively, at 4 weeks (P = 0.014 and
      P = 0.003). At 8 weeks there was an 18-26% reduction in wound size (P = 0.04) in
      the remaining patients. Wound-related pain measured by the visual analogue pain
      scale and the wound pain scale declined 60% (P = 0.024) and 70% (P = 0.001),
      respectively. Patient and clinician satisfaction remained positive throughout the
      treatment period. It is concluded that treatment with CACIPLIQ20 significantly
      improved wound-related pain and may facilitate wound healing. Patient and
      clinician satisfaction remained high throughout the trial.

PMID- 21078133
TI  - Linkage disequilibrium reveals different demographic history in egg laying
      chickens.
AB  - BACKGROUND: The availability of larger-scale SNP data sets in the chicken genome
      allows to achieve a higher resolution of the pattern of linkage disequilibrium
      (LD). In this study, 36 k and 57 k genotypes from two independent genotyping
      chips were used to systematically characterize genome-wide extent and structure
      of LD in the genome of four chicken populations. In total, we analyzed genotypes
      of 454 animals from two commercial and two experimental populations of white and
      brown layers which allows to some extent a generalization of the results.
      RESULTS: The number of usable SNPs in this study was 19 k to 37 k in brown layers
      and 8 k to 19 k in white layers. Our analyzes showed a large difference of LD
      between the lines of white and brown layers. A mean value of r2 = 0.73 +/- 0.36
      was observed in pair-wise distances of < 25 Kb for commercial white layers, and
      it dropped to 0.60 +/- 0.38 with distances of 75 to 120 Kb, the interval which
      includes the average inter-marker space in this line. In contrast, an overall
      mean value of r2= 0.32 +/- 0.33 was observed for SNPs less than 25 Kb apart from
      each other and dropped to 0.21 +/- 0.26 at a distance of 100 kb in commercial
      brown layers. There was a remarkable similarity of the LD patterns among the two
      populations of white layers. The same was true for the two populations of brown
      layers, while the LD pattern between white and brown layers was clearly
      different. Inferring the population demographic history from LD data resulted in
      a larger effective population size in brown than white populations, reflecting
      less inbreeding among brown compared to white egg layers. CONCLUSIONS: We report
      comprehensive LD map statistics for the genome of egg laying chickens with an up
      to 3 times higher resolution compared to the maps available so far. The results
      were found to be consistent between analyzes based on the parallel SNP chips and
      across different populations (commercial vs. experimental) within the brown and
      the white layers. It is concluded that the current density of usable markers in
      this study is sufficient for association mapping and the implementation of
      genomic selection in these populations to achieve a similar accuracy as in
      implementations of association mapping and genomic selection in mammalian farm
      animals.

PMID- 21078134
TI  - Role of the trigeminal mesencephalic nucleus in rat whisker pad proprioception.
AB  - BACKGROUND: Trigeminal proprioception related to rodent macrovibrissae movements
      is believed to involve skin receptors on the whisker pad because pad muscles
      operate without muscle spindles. This study was aimed to investigate in rats
      whether the trigeminal mesencephalic nucleus (TMnu), which provides
      proprioceptive feedback for chewing muscles, may be also involved in whisker pad
      proprioception. METHODS: Two retrograde tracers, Dil and True Blue Chloride, were
      injected into the mystacial pad and the masseter muscle on the same side of
      deeply anesthetized rats to label the respective projecting sensory neurons. This
      double-labeling technique was used to assess the co-innervation of both
      structures by the trigeminal mesencephalic nucleus (TMnu).In a separate group of
      anesthetized animals, the spontaneous electrical activities of TMnu neurons were
      analyzed by extracellular recordings during spontaneous movements of the
      macrovibrissae. Mesencephalic neurons (TMne) were previously identified by their
      responses to masseter muscle stretching. Changes in TMne spontaneous electrical
      activities, analyzed under baseline conditions and during whisking movements,
      were statistically evaluated using Student's t-test for paired observations.
      RESULTS: Neuroanatomical experiments revealed different subpopulations of
      trigeminal mesencephalic neurons: i) those innervating the neuromuscular spindles
      of the masseter muscle, ii) those innervating the mystacial pad, and iii) those
      innervating both structures. Extracellular recordings made during spontaneous
      movements of the macrovibrisae showed that whisking neurons similar to those
      observed in the trigeminal ganglion were located in the TMnu. These neurons had
      different patterns of activation, which were dependent on the type of spontaneous
      macrovibrissae movement. In particular, their spiking activity tonically
      increased during fan-like movements of the vibrissae and showed phasic bursting
      during rhythmic whisking. Furthermore, the same neurons may also respond to
      masseter muscle stretch. CONCLUSIONS: results strongly support the hypothesis
      that the TMnu also contains first-order neurons specialized for relaying spatial
      information related to whisker movement and location to trigeminal-cortical
      pathways. In fact, the TMnu projects to second-order trigeminal neurons, thus
      allowing the rat brain to deduce higher-order information regarding executed
      movements of the vibrissae by combining touch information carried by trigeminal
      ganglion neurons with proprioceptive information carried by mesencephalic
      neurons.

PMID- 21078135
TI  - Simplified routines in prescribing physical activity can increase the amount of
      prescriptions by doctors, more than economic incentives only: an observational
      intervention study.
AB  - BACKGROUND: Physical inactivity is one well-known risk factor related to disease.
      Physical activity on prescription (PAP) has been shown in some studies to be a
      successful intervention for increasing physical activity among patients with a
      sedentary lifestyle. The method involves motivational counselling that can be
      time-consuming for the prescribing doctor and might be a reason why physical
      activity on prescription is not used more frequently. This study might show a way
      to make the method of prescribing physical activity more user-friendly. The
      purpose is to determine whether a change in procedures increases the use of
      physical activity on prescription, and thus the aim of this study is to describe
      the methodology used. RESULTS: The observational intervention study included an
      intervention group consisting of one Primary Health Care (PHC) clinic and a
      control group consisting of six PHC clinics serving 149,400 inhabitants in the
      County of Blekinge, Sweden.An economic incentive was introduced in both groups
      when prescribing physical activity on prescription. In the intervention group, a
      change was made to the process of prescribing physical activity, together with
      information and guidance to the personnel working at the clinics. Physical
      therapists were used in the process of carrying out the prescription, conducting
      the motivational interview and counselling the patient. This methodology was used
      to minimise the workload of the physician. The chi-2 test was used for studying
      differences between the two groups. PAP prescribed by doctors increased eightfold
      in the intervention group compared to the control group. The greatest increase of
      PAP was seen among physicians in the intervention group as compared to all other
      professionals in the control group. The economic incentive gave a significant but
      smaller increase of PAP by doctors. CONCLUSION: By simplifying and developing
      PAP, this study has shown a concrete way to increase the implementation of
      physical activity on prescription in general practice, as opposed to what can be
      gained by an economic bonus system alone. This study indicates that a bonus
      system may not be enough to implement an evidence-based method.

PMID- 21078136
TI  - Laxative effects of agarwood on low-fiber diet-induced constipation in rats.
AB  - BACKGROUND: Agarwood (Aquilaria sinensis), well known as incense in Southeast
      Asia, has been used as a digestive in traditional medicine. We investigated the
      laxative effects of an ethanol extract of agarwood leaves (EEA) in a rat model of
      low-fiber diet-induced constipation. METHODS: A set of rats was bred on a normal
      diet while another set was placed on a low-fiber diet to induce constipation. The
      laxative effect of agarwood was then investigated on both sets of rats. RESULTS:
      Pretreatment of normal rats with single dose of EEA (600 mg/kg, p.o.)
      significantly increased frequency and weight of stools. Also, treatments with EEA
      (300 and 600 mg/kg, p.o.) for 14 days caused a significant increase in stool
      frequency and weight. Feeding of the animals with a low-fiber diet resulted in a
      decrease in stool weight, frequency, and water content and also delayed carmine
      egestion. A single treatment with EEA (600 mg/kg) or senna (150 and 300 mg/kg)
      significantly increased stool frequency, weight, and water content and also
      accelerated carmine egestion in the model rats. Once daily administrations of EEA
      (150 mg/kg), for 14 days, caused a significant increase in water content of
      stools. The higher doses of EEA (300 and 600 mg/kg) significantly increased
      frequency, weight, and water content of the stools while accelerating carmine
      egestion in the constipated rats. Senna (150 and 300 mg/kg) produced similar
      effect as the higher doses of EEA but, in addition, induced severe diarrhea.
      CONCLUSION: These findings indicate that EEA has a laxative effect, without
      causing diarrhea, in a rat model of low-fiber diet-induced constipation. These
      findings suggest that EEA may be highly effective on constipation as a
      complementary medicine in humans suffering from life style-induced constipation.

PMID- 21078137
TI  - Avian influenza A (H9N2): computational molecular analysis and phylogenetic
      characterization of viral surface proteins isolated between 1997 and 2009 from
      the human population.
AB  - BACKGROUND: H9N2 avian influenza A viruses have become panzootic in Eurasia over
      the last decade and have caused several human infections in Asia since 1998. To
      study their evolution and zoonotic potential, we conducted an in silico analysis
      of H9N2 viruses that have infected humans between 1997 and 2009 and identified
      potential novel reassortments. RESULTS: A total of 22 hemagglutinin (HA) and
      neuraminidase (NA) nucleotide and deduced amino acid sequences were retrieved
      from the NCBI flu database. It was identified that mature peptide sequences of HA
      genes isolated from humans in 2009 had glutamine at position 226 (H3) of the
      receptor binding site, indicating a preference to bind to the human alpha (2-6)
      sialic acid receptors, which is different from previously isolated viruses and
      studies where the presence of leucine at the same position contributes to
      preference for human receptors and presence of glutamine towards avian receptors.
      Similarly, strains isolated in 2009 possessed new motif R-S-N-R in spite of
      typical R-S-S-R at the cleavage site of HA, which isn't reported before for H9N2
      cases in humans. Other changes involved loss, addition, and variations in
      potential glycosylation sites as well as in predicted epitopes. The results of
      phylogenetic analysis indicated that HA and NA gene segments of H9N2 including
      those from current and proposed vaccine strains belong to two different Eurasian
      phylogenetic lineages confirming possible genetic reassortments. CONCLUSIONS:
      These findings support the continuous evolution of avian H9N2 viruses towards
      human as host and are in favor of effective surveillance and better
      characterization studies to address this issue.

PMID- 21078138
TI  - Gene expression in developing fibres of Upland cotton (Gossypium hirsutum L.) was
      massively altered by domestication.
AB  - BACKGROUND: Understanding the evolutionary genetics of modern crop phenotypes has
      a dual relevance to evolutionary biology and crop improvement. Modern upland
      cotton (Gossypium hirsutum L.) was developed following thousands of years of
      artificial selection from a wild form, G. hirsutum var. yucatanense, which bears
      a shorter, sparser, layer of single-celled, ovular trichomes ('fibre'). In order
      to gain an insight into the nature of the developmental genetic transformations
      that accompanied domestication and crop improvement, we studied the
      transcriptomes of cotton fibres from wild and domesticated accessions over a
      developmental time course. RESULTS: Fibre cells were harvested between 2 and 25
      days post-anthesis and encompassed the primary and secondary wall synthesis
      stages. Using amplified messenger RNA and a custom microarray platform designed
      to interrogate expression for 40,430 genes, we determined global patterns of
      expression during fibre development. The fibre transcriptome of domesticated
      cotton is far more dynamic than that of wild cotton, with over twice as many
      genes being differentially expressed during development (12,626 versus 5273).
      Remarkably, a total of 9465 genes were diagnosed as differentially expressed
      between wild and domesticated fibres when summed across five key developmental
      time points. Human selection during the initial domestication and subsequent crop
      improvement has resulted in a biased upregulation of components of the
      transcriptional network that are important for agronomically advanced fibre,
      especially in the early stages of development. About 15% of the differentially
      expressed genes in wild versus domesticated cotton fibre have no homology to the
      genes in databases. CONCLUSIONS: We show that artificial selection during crop
      domestication can radically alter the transcriptional developmental network of
      even a single-celled structure, affecting nearly a quarter of the genes in the
      genome. Gene expression during fibre development within accessions and expression
      alteration arising from evolutionary change appears to be 'modular' - complex
      genic networks have been simultaneously and similarly transformed, in a
      coordinated fashion, as a consequence of human-mediated selection. These results
      highlight the complex alteration of the global gene expression machinery that
      resulted from human selection for a longer, stronger and finer fibre, as well as
      other aspects of fibre physiology that were not consciously selected. We
      illustrate how the data can be mined for genes that were unwittingly targeted by
      aboriginal and/or modern domesticators during crop improvement and/or which
      potentially control the improved qualities of domesticated cotton fibre.See
      Commentary: http://www.biomedcentral.com/1741-7007/8/137.

PMID- 21078139
TI  - Geographical variation in cardiovascular incidence: results from the British
      Women's Heart and Health Study.
AB  - BACKGROUND: Prevalence of cardiovascular disease (CVD) in women shows regional
      variations not explained by common risk factors. Analysis of CVD incidence will
      provide insight into whether there is further divergence between regions with
      increasing age. METHODS: Seven-year follow-up data on 2685 women aged 59-80 (mean
      69) at baseline from 23 towns in the UK were available from the British Women's
      Heart and Health Study. Time to fatal or non-fatal CVD was analyzed using Cox
      regression with adjustment for risk factors, using multiple imputation for
      missing values. RESULTS: Compared to South England, CVD incidence is similar in
      North England (HR 1.05 (95% CI 0.84, 1.31)) and Scotland (0.93 (0.68, 1.27)), but
      lower in Midlands/Wales (0.85 (0.64, 1.12)). Event severity influenced regional
      variation, with South England showing lower fatal incident CVD than other
      regions, but higher non-fatal incident CVD. Kaplan-Meier plots suggested that
      regional divergence in CVD occurred before baseline (before mean baseline age of
      69). CONCLUSIONS: In women, regional differences in CVD early in adult life do
      not further diverge in later life. This may be due to regional differences in
      early detection, survivorship of women entering the study, or event severity.
      Targeting health care resources for CVD by geographic variation may not be
      appropriate for older age-groups.

PMID- 21078140
TI  - Long-term results of diaphragmatic plication in adults with unilateral diaphragm
      paralysis.
AB  - BACKGROUND: In this study we aimed to evaluate the long-term outcome of
      diaphragmatic plication for symptomatic unilateral diaphragm paralysis. METHODS:
      Thirteen patients who underwent unilateral diaphragmatic plication (2 patients
      had right, 11 left plication) between January 2003 and December 2006 were
      evaluated. One patient died postoperatively due to sepsis. The remaining 12
      patients [9 males, 3 females; mean age 60 (36-66) years] were reevaluated with
      chest radiography, flouroscopy or ultrasonography, pulmonary function tests,
      computed tomography (CT) or magnetic resonance imaging (MRI), and the MRC/ATS
      dyspnea score at an average of 5.4 (4-7) years after diaphragmatic plication.
      RESULTS: The etiology of paralysis was trauma (9 patients), cardiac by pass
      surgery (3 patients), and idiopathic (1 patient). The principle symptom was
      progressive dyspnea with a mean duration of 32.9 (22-60) months before surgery.
      All patients had an elevated hemidiaphragm and paradoxical movement
      radiologically prior to surgery. There were partial atelectasis and reccurent
      infection of the lower lobe in the affected side on CT in 9 patients. Atelectasis
      was completely improved in 9 patients after plication. Preoperative spirometry
      showed a clear restrictive pattern. Mean preoperative FVC was 56.7 +/- 11.6% and
      FEV1 65.3 +/- 8.7%. FVC and FEV1 improved by 43.6 +/- 30.6% (p < 0.001) and 27.3
      +/- 10.9% (p < 0.001) at late follow-up. MRC/ATS dyspnea scores improved 3 points
      in 11 patients and 1 point in 1 patient at long-term (p < 0.0001). Eight patients
      had returned to work at 3 months after surgery. CONCLUSIONS: Diaphragmatic
      plication for unilateral diaphragm paralysis decreases lung compression, ensures
      remission of symptoms, and improves quality of life in long-term period.

PMID- 21078141
TI  - Anaplasma phagocytophilum infection in a domestic cat in Finland: Case report.
AB  - BACKGROUND: Anaplasmosis is a vectorborne disease caused by the gram-negative
      bacterium Anaplasma phagocytophilum. This species displays positive tropism to
      granulocytes and can cause illness in several mammalian species, including cats,
      dogs, and humans. It is considered as an emerging disease in Europe. The clinical
      signs are nonspecific and include fever, lethargy, and inappetence. The most
      typical hematologic abnormality is thrombocytopenia. A tentative diagnosis can be
      made by detecting intracytoplasmic morulae inside neutrophils. The diagnosis is
      confirmed by PCR and serology in paired serum samples. A sample for PCR analysis
      should be taken before treatment. Anaplasmosis is treated with doxycycline. CASE
      PRESENTATION: A feline case of anaplasmosis is presented. The history, clinical
      presentation, diagnostics, treatment, and follow-up are discussed. CONCLUSIONS:
      This case indicates that Anaplasma phagocytophilum infects cats in Finland. To
      provide accurate treatment, anaplasmosis should be listed as a differential
      diagnosis in cats suffering from acute febrile illness with previous tick
      exposure.

PMID- 21078142
TI  - Health-related quality of life in relapsing remitting multiple sclerosis patients
      during treatment with glatiramer acetate: a prospective, observational,
      international, multi-centre study.
AB  - BACKGROUND: Glatiramer acetate (GA) and interferon-beta (INFb) are first-line
      disease modifying drugs for relapsing remitting multiple sclerosis (RRMS).
      Treatment with INFb is associated with a significant increase in health-related
      quality of life (HR-QoL) in the first 12 months. It is not known whether HR-QoL
      increases during treatment with GA. METHODS: 197 RRMS patients, 106 without and
      91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds
      Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32), fatigue (Fatigue
      Impact Scale [FIS]) and depressed mood (Beck Depression Inventory-Short Form [BDI
      SF]) at baseline and 6 and 12 months after start of GA treatment. RESULTS: At 6
      and 12 months mean LMS-QoL scores were significantly increased in the treatment
      naive patient group (p < 0.001), not in the pre-treated group. At month 12 43% of
      treatment-naive patients had improved HR-QoL (increase LMS-QoL score 3 or more
      points) (p < 0.001). Likewise, mean FIS scores were decreased at months 6 and 12
      in the treatment-naive group (p < 0.01), not in the pre-treated group. In both
      groups mean BDI-SF scores did not change. No demographic or clinical baseline
      factor was predictive of HR-QoL increase. HR-QoL changes were zero to negative
      for patients who had discontinued GA before month 12 (28.4% of patients).
      CONCLUSIONS: In RRMS patients without prior immunomodulation/immunosuppression
      treatment with GA was associated with an increase in HR-QoL in the first 6
      months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved.
      Increase in HR-QoL was associated with decrease in fatigue.

PMID- 21078143
TI  - Designing coarse grained-and atom based-potentials for protein-protein docking.
AB  - BACKGROUND: Protein-protein docking is a challenging computational problem in
      functional genomics, particularly when one or both proteins undergo
      conformational change(s) upon binding. The major challenge is to define a scoring
      function soft enough to tolerate these changes and specific enough to distinguish
      between near-native and "misdocked" conformations. RESULTS: Using a linear
      programming (LP) technique, we developed two types of potentials: (i) Side chain
      based and (ii) Heavy atom-based. To achieve this we considered a set of 161
      transient complexes and generated a large set of putative docked structures
      (decoys), based on a shape complementarity criterion, for each complex. The
      demand on the potentials was to yield, for the native (correctly docked)
      structure, a potential energy lower than those of any of the non-native
      (misdocked) structures. We show that the heavy atom-based potentials were able to
      comply with this requirement but not the side chain-based one. Thus, despite the
      smaller number of parameters, the capability of heavy atom-based potentials to
      discriminate between native and "misdocked" conformations is improved relative to
      those of the side chain-based potentials. The performance of the atom-based
      potentials was evaluated by a jackknife test on a set of 50 complexes taken from
      the Zdock2.3 decoys set. CONCLUSIONS: Our results show that, using the LP
      approach, we were able to train our potentials using a dataset of transient
      complexes only the newly developed potentials outperform three other known
      potentials in this test.

PMID- 21078144
TI  - Mutation accumulation in Tetrahymena.
AB  - BACKGROUND: The rate and fitness effects of mutations are key in understanding
      the evolution of every species. Traditionally, these parameters are estimated in
      mutation accumulation experiments where replicate lines are propagated in
      conditions that allow mutations to randomly accumulate without the purging effect
      of natural selection. These experiments have been performed with many model
      organisms but we still lack empirical estimates of the rate and effects of
      mutation in the protists. RESULTS: We performed a mutation accumulation (MA)
      experiment in Tetrahymena thermophila, a species that can reproduce sexually and
      asexually in nature, and measured both the mean decline and variance increase in
      fitness of 20 lines. The results obtained with T. thermophila were compared with
      T. pyriformis that is an obligate asexual species. We show that MA lines of T.
      thermophila go to extinction at a rate of 1.25 clonal extinctions per bottleneck.
      In contrast, populations of T. pyriformis show a much higher resistance to
      extinction. Variation in gene copy number is likely to be a key factor in
      explaining these results, and indeed we show that T. pyriformis has a higher mean
      copy number per cell than T. thermophila. From fitness measurements during the MA
      experiment, we infer a rate of mutation to copy number variation of 0.0333 per
      haploid MAC genome of T. thermophila and a mean effect against copy number
      variation of 0.16. A strong effect of population size in the rate of fitness
      decline was also found, consistent with the increased power of natural selection.
      CONCLUSIONS: The rate of clonal extinction measured for T. thermophila is
      characteristic of a mutational degradation and suggests that this species must
      undergo sexual reproduction to avoid the deleterious effects detected in the
      laboratory experiments. We also suggest that an increase in chromosomal copy
      number associated with the phenotypic assortment of amitotic divisions can
      provide an alternative mechanism to escape the deleterious effect of random
      chromosomal copy number variation in species like T. pyriformis that lack the
      resetting mechanism of sexual reproduction. Our results are relevant to the
      understanding of cell line longevity and senescence in ciliates.

PMID- 21078145
TI  - Whole abdomen radiation therapy in ovarian cancers: a comparison between fixed
      beam and volumetric arc based intensity modulation.
AB  - PURPOSE: A study was performed to assess dosimetric characteristics of volumetric
      modulated arcs (RapidArc, RA) and fixed field intensity modulated therapy (IMRT)
      for Whole Abdomen Radiotherapy (WAR) after ovarian cancer. METHODS AND MATERIALS:
      Plans for IMRT and RA were optimised for 5 patients prescribing 25 Gy to the
      whole abdomen (PTV_WAR) and 45 Gy to the pelvis and pelvic nodes (PTV_Pelvis)
      with Simultaneous Integrated Boost (SIB) technique. Plans were investigated for 6
      MV (RA6, IMRT6) and 15 MV (RA15, IMRT15) photons. Objectives were: for both PTVs
      V90% > 95%, for PTV_Pelvis: Dmax < 105%; for organs at risk, maximal sparing was
      required. The MU and delivery time measured treatment efficiency. Pre-treatment
      Quality assurance was scored with Gamma Agreement Index (GAI) with 3% and 3 mm
      thresholds. RESULTS: IMRT and RapidArc resulted comparable for target coverage.
      For PTV_WAR, V90% was 99.8 +/- 0.2% and 93.4 +/- 7.3% for IMRT6 and IMRT15, and
      98.4 +/- 1.7 and 98.6 +/- 0.9% for RA6 and RA15. Target coverage resulted
      improved for PTV_Pelvis. Dose homogeneity resulted slightly improved by RA
      (Uniformity was defined as U5-95% = D5%-D95%/Dmean). U5-95% for PTV_WAR was 0.34
      +/- 0.05 and 0.32 +/- 0.06 (IMRT6 and IMRT15), 0.30 +/- 0.03 and 0.26 +/- 0.04
      (RA6 and RA15); for PTV_Pelvis, it resulted equal to 0.1 for all techniques. For
      organs at risk, small differences were observed between the techniques. MU
      resulted 3130 +/- 221 (IMRT6), 2841 +/- 318 (IMRT15), 538 +/- 29 (RA6), 635 +/-
      139 (RA15); the average measured treatment time was 18.0 +/- 0.8 and 17.4 +/- 2.2
      minutes (IMRT6 and IMRT15) and 4.8 +/- 0.2 (RA6 and RA15). GAIIMRT6 = 97.3 +/-
      2.6%, GAIIMRT15 = 94.4 +/- 2.1%, GAIRA6 = 98.7 +/- 1.0% and GAIRA15 = 95.7 +/-
      3.7%. CONCLUSION: RapidArc showed to be a solution to WAR treatments offering
      good dosimetric features with significant logistic improvements compared to IMRT.

PMID- 21078146
TI  - Health-related quality of life in a clinical sample of obese children and
      adolescents.
AB  - BACKGROUND: Obesity affects ethnic minority groups disproportionately, especially
      in the pediatric population. However, little is known about the impact of obesity
      on health-related quality of life (HRQoL) in children and adolescents from mixed
      ethnic samples. The purpose of this study was to: 1) measure HRQoL in a mixed
      ethnic clinical sample of obese children and adolescents, 2) compare HRQoL
      assessments in obese participants and healthy controls, and 3) compare HRQoL in
      obese children and adolescents according to their pubertal status. METHODS: A
      clinical sample of children and adolescents with obesity (n = 96) and healthy
      children and adolescents attending local schools (n = 444) completed the
      Pediatric Quality of Life Inventory (PedsQL; UK version 4). Age-appropriate
      versions were self-administered by children and adolescents aged 8-18 years, and
      interview administered to children aged 5-7 years. Multiple regression analyses
      controlling for age, gender, pubertal status, and ethnicity were used to compare
      the PedsQL scores of the two samples. RESULTS: The clinical sample of obese
      children and adolescents had poorer HRQoL scores on all dimensions of the PedsQL
      compared to the healthy controls (p < 0.005). Subsequent analyses also
      demonstrated that in this sample of mixed-ethnic children and adolescents,
      prepubescent obese children achieved the poorest scores in the emotional
      functioning dimension. CONCLUSIONS: Obesity significantly impacts on physical,
      emotional, social and school functioning of mixed-ethnic children and
      adolescents. Clinicians need to be aware of the significant impact of obesity on
      all aspects of functioning. More effort is required to target interventions to
      improve the quality of life of children with obesity.

PMID- 21078147
TI  - Insect cells are superior to Escherichia coli in producing malaria proteins
      inducing IgG targeting PfEMP1 on infected erythrocytes.
AB  - BACKGROUND: The PFD1235w Plasmodium falciparum erythrocyte membrane protein 1
      (PfEMP1) antigen is associated with severe malaria in children and can be
      expressed on the surface of infected erythrocytes (IE) adhering to ICAM1.
      However, the exact three-dimensional structure of this PfEMP1 and its surface
      exposed epitopes are unknown. An insect cell and Escherichia coli based system
      was used to express single and double domains encoded by the pfd1235w var gene.
      The resulting recombinant proteins have been evaluated for yield and purity and
      their ability to induce rat antibodies, which react with the native PFD1235w
      PfEMP1 antigen expressed on 3D7PFD1235w-IE. Their recognition by human anti
      malaria antibodies from previously infected Tanzanian donors was also analysed.
      METHODS: The recombinant proteins were run on SDS-PAGE and Western blots for
      quantification and size estimation. Insect cell and E. coli-produced recombinant
      proteins were coupled to a bead-based Luminex assay to measure the plasma
      antibody reactivity of 180 samples collected from Tanzanian individuals. The
      recombinant proteins used for immunization of rats and antisera were also tested
      by flow cytometry for their ability to surface label 3D7PFD1235w-IE. RESULTS: All
      seven pAcGP67A constructs were successfully expressed as recombinant protein in
      baculovirus-infected insect cells and subsequently produced to a purity of 60-97%
      and a yield of 2-15 mg/L. By comparison, only three of seven pET101/D-TOPO
      constructs expressed in the E. coli system could be produced at all with purity
      and yield ranging from 3-95% and 6-11 mg/L. All seven insect cell, but only two
      of the E. coli produced proteins induced antibodies reactive with native PFD1235w
      expressed on 3D7PFD1235w-IE. The recombinant proteins were recognized in an age-
      and transmission intensity-dependent manner by antibodies from 180 Tanzanian
      individuals in a bead-based Luminex assay. CONCLUSIONS: The baculovirus based
      insect cell system was distinctly superior to the E. coli expression system in
      producing a larger number of different recombinant PFD1235w protein domains and
      these were significantly easier to purify at a useful yield. However, proteins
      produced in both systems were able to induce antibodies in rats, which can
      recognize the native PFD1235w on the surface of IE.

PMID- 21078148
TI  - Identification of losses to follow-up in a community-based antiretroviral therapy
      clinic in South Africa using a computerized pharmacy tracking system.
AB  - BACKGROUND: High rates of loss to follow-up (LTFU) are undermining rapidly
      expanding antiretroviral treatment (ART) services in sub-Saharan Africa. The
      intelligent dispensing of ART (iDART) is an open-source electronic pharmacy
      system that provides an efficient means of generating lists of patients who have
      failed to pick-up medication. We determined the duration of pharmacy delay that
      optimally identified true LTFU. METHODS: We conducted a retrospective cross
      sectional study of a community-based ART cohort in Cape Town, South Africa. We
      used iDART to identify groups of patients known to be still enrolled in the
      cohort on the 1st of April 2008 that had failed to pick-up medication for periods
      of >= 6, >= 12, >= 18 and >= 24 weeks. We defined true LTFU as confirmed failure
      to pick up medication for 3 months since last attendance. We then assessed short
      term and long-term outcomes using a prospectively maintained database and patient
      records. RESULTS: On the date of the survey, 2548 patients were registered as
      receiving ART but of these 85 patients (3.3%) were found to be true LTFU. The
      numbers of individuals (proportion of the cohort) identified by iDART as having
      failed to collect medication for periods of >= 6, >= 12, >= 18 and >= 24 weeks
      were 560 (22%), 194 (8%), 117 (5%) and 80 (3%), respectively. The sensitivities
      of these pharmacy delays for detecting true LTFU were 100%, 100%, 62.4% and
      47.1%, respectively. The corresponding specificities were 80.7%, 95.6%, 97.4% and
      98.4%. Thus, the optimal delay was >= 12 weeks since last attendance at this
      clinic (equivalent to 8 weeks since medication ran out). Pharmacy delays were
      also found to be significantly associated with LTFU and death one year later.
      CONCLUSIONS: The iDART electronic pharmacy system can be used to detect patients
      potentially LTFU and who require recall. Using a short a cut-off period was too
      non-specific for LTFU and would require the tracing of very large numbers of
      patients. Conversely prolonged delays were too insensitive. Of the periods
      assessed, a >= 12 weeks delay appeared optimal. This system requires prospective
      evaluation to further refine its utility.

PMID- 21078149
TI  - Nitroglycerin can facilitate weaning of difficult-to-wean chronic obstructive
      pulmonary disease patients: a prospective interventional non-randomized study.
AB  - INTRODUCTION: Both experimental and clinical data give convincing evidence to
      acute cardiac dysfunction as the origin or a cofactor of weaning failure in
      patients with chronic obstructive pulmonary disease. Therefore, treatment
      targeting the cardiovascular system might help the heart to tolerate more
      effectively the critical period of weaning. This study aims to assess the
      hemodynamic, respiratory and clinical effects of nitroglycerin infusion in
      difficult-to-wean patients with severe chronic obstructive pulmonary disease.
      METHODS: Twelve difficult-to-wean (failed >= 3 consecutive trials) chronic
      obstructive pulmonary disease patients, who presented systemic arterial
      hypertension (systolic blood pressure >= 140 mmHg) during weaning failure and had
      systemic and pulmonary artery catheters in place, participated in this
      prospective, interventional, non-randomized clinical trial. Patients were studied
      in two consecutive days, i.e., the first day without (Control day) and the second
      day with (Study day) nitroglycerin continuous intravenous infusion starting at
      the beginning of the spontaneous breathing trial, and titrated to maintain normal
      systolic blood pressure. Hemodynamic, oxygenation and respiratory measurements
      were performed on mechanical ventilation, and during a 2-hour T-piece spontaneous
      breathing trial. Primary endpoint was hemodynamic and respiratory effects of
      nitroglycerin infusion. Secondary endpoint was spontaneous breathing trial and
      extubation outcome. RESULTS: Compared to mechanical ventilation, mean systemic
      arterial pressure, rate-pressure product, mean pulmonary arterial pressure, and
      pulmonary artery occlusion pressure increased [from (mean +/- SD) 94 +/- 14,
      13708 +/- 3166, 29.9 +/- 4.8, and 14.8 +/- 3.8 to 109 +/- 20 mmHg, 19856 +/- 4877
      mmHg b/min, 41.6 +/- 5.8 mmHg, and 23.4 +/- 7.4 mmHg, respectively], and mixed
      venous oxygen saturation decreased (from 75.7 +/- 3.5 to 69.3 +/- 7.5%) during
      failing trials on Control day, whereas they did not change on Study day. Venous
      admixture increased throughout the trial on both Control day and Study day, but
      this increase was lower on Study day. Whereas weaning failed in all patients on
      Control day, nitroglycerin administration on Study day enabled a successful
      spontaneous breathing trial and extubation in 92% and 88% of patients,
      respectively. CONCLUSIONS: In this clinical setting, nitroglycerin infusion can
      expedite the weaning by restoring weaning-induced cardiovascular compromise.

PMID- 21078150
TI  - Associations between depressive symptoms, sexual behaviour and relationship
      characteristics: a prospective cohort study of young women and men in the Eastern
      Cape, South Africa.
AB  - BACKGROUND: Psychological factors are often neglected in HIV research, although
      psychological distress is common in low- to middle-income countries, such as
      South Africa. There is a need to deepen our understanding of the role of mental
      health factors in the HIV epidemic. We set out to investigate whether baseline
      depressive symptomatology was associated with risky sexual behaviour and
      relationship characteristics of men and women at baseline, as well as those found
      12 months later. METHODS: We used prospective cohort data from a cluster
      randomized controlled trial of an HIV prevention intervention in the Eastern Cape
      Province of South Africa. Our subjects were 1002 female and 976 male volunteers
      aged 15 to 26. Logistic regression was used to model the cross-sectional and
      prospective associations between baseline depressive symptomatology, risky sexual
      behaviors and relationship characteristics. The analysis adjusted for the
      clustering effect, study design, intervention and several confounding variables.
      RESULTS: Prevalence of depressive symptoms was 21.1% among women and 13.6% among
      men. At baseline, women with depressed symptoms were more likely to report
      lifetime intimate partner violence (AOR = 2.56, 95% CI 1.89-3.46) and have dated
      an older partner (AOR = 1.37, 95% CI 1.03-1.83). A year later, baseline
      depressive symptomatology was associated with transactional sex (AOR = 2.60, 95%
      CI 1.37, 4.92) and intimate partner violence (AOR = 1.67, 95% CI 1.18-2.36) in
      the previous 12 months. Men with depressive symptoms were more likely to report
      ever having had transactional sex (AOR = 1.48, 95% CI 1.01-2.17), intimate
      partner violence perpetration (AOR = 1.50, 95% CI 0.98-2.28) and perpetration of
      rape (AOR = 1.81, 95% CI 1.14-2.87). They were less likely to report correct
      condom use at last sex (AOR = 0.50, 95% CI 0.32-0.78). A year later, baseline
      depressive symptomatology was associated with failure to use a condom at last sex
      among men (AOR = 0.60, 95% CI 0.40-0.89). CONCLUSIONS: Symptoms of depression
      should be considered as potential markers of increased HIV risk and this
      association may be causal. HIV prevention needs to encompass promotion of
      adolescent mental health.

PMID- 21078151
TI  - The emerging role of insulin-like growth factor 1 receptor (IGF1r) in
      gastrointestinal stromal tumors (GISTs).
AB  - Recent years have seen a growing interest in insulin-like growth factor 1
      receptor (IGF1R) in medical oncology. Interesting data have been reported also on
      IGF1r in gastrointestinal stromal tumors (GISTs) especially in children and in
      young adult patients whose disease does not harbour mutations on KIT and PDGFRA
      and are poorly responsive to conventional therapies. However, it is too early to
      reach conclusions on IGF1R as a novel therapeutic target in GIST because the
      receptor's biological role is still to be defined and the clinical significance
      in patients needs to be studied in larger studies. We update and comment the
      current literature on IGF1R in GISTs and discuss the future perspectives in this
      promising field.

PMID- 21078152
TI  - A large-scale electrophoresis- and chromatography-based determination of gene
      expression profiles in bovine brain capillary endothelial cells after the re
      induction of blood-brain barrier properties.
AB  - BACKGROUND: Brain capillary endothelial cells (BCECs) form the physiological
      basis of the blood-brain barrier (BBB). The barrier function is (at least in
      part) due to well-known proteins such as transporters, tight junctions and
      metabolic barrier proteins (e.g. monoamine oxidase, gamma glutamyltranspeptidase
      and P-glycoprotein). Our previous 2-dimensional gel proteome analysis had
      identified a large number of proteins and revealed the major role of dynamic
      cytoskeletal remodelling in the differentiation of bovine BCECs. The aim of the
      present study was to elaborate a reference proteome of Triton X-100-soluble
      species from bovine BCECs cultured in the well-established in vitro BBB model
      developed in our laboratory. RESULTS: A total of 215 protein spots (corresponding
      to 130 distinct proteins) were identified by 2-dimensional gel electrophoresis,
      whereas over 350 proteins were identified by a shotgun approach. We classified
      around 430 distinct proteins expressed by bovine BCECs. Our large-scale gene
      expression analysis enabled the correction of mistakes referenced into protein
      databases (e.g. bovine vinculin) and constitutes valuable evidence for
      predictions based on genome annotation. CONCLUSIONS: Elaboration of a reference
      proteome constitutes the first step in creating a gene expression database
      dedicated to capillary endothelial cells displaying BBB characteristics. It
      improves of our knowledge of the BBB and the key proteins in cell structures,
      cytoskeleton organization, metabolism, detoxification and drug resistance.
      Moreover, our results emphasize the need for both appropriate experimental design
      and correct interpretation of proteome datasets.

PMID- 21078156
TI  - Correction: Addison's disease presenting with idiopathic intracranial
      hypertension in 24-year-old woman: a case report.

PMID- 21078155
TI  - Risk of infection and adverse outcomes among pregnant working women in selected
      occupational groups: A study in the Danish National Birth Cohort.
AB  - BACKGROUND: Exposure to infectious pathogens is a frequent occupational hazard
      for women who work with patients, children, animals or animal products. The
      purpose of the present study is to investigate if women working in occupations
      where exposure to infections agents is common have a high risk of infections and
      adverse pregnancy outcomes. METHODS: We used data from the Danish National Birth
      Cohort, a population-based cohort study and studied the risk of Infection and
      adverse outcomes in pregnant women working with patients, with children, with
      food products or with animals. The regression analysis were adjusted for the
      following covariates: maternal age, parity, history of miscarriage, socio
      occupational status, pre-pregnancy body mass index, smoking habit, alcohol
      consumption. RESULTS: Pregnant women who worked with patients or children or food
      products had an excess risk of sick leave during pregnancy for more than three
      days. Most of negative reproductive outcomes were not increased in these
      occupations but the prevalence of congenital anomalies (CAs) was slightly higher
      in children of women who worked with patients. The prevalence of small for
      gestational age infants was higher among women who worked with food products.
      There was no association between occupation infections during pregnancy and the
      risk of reproductive failures in the exposed groups. However, the prevalence of
      CAs was slightly higher among children of women who suffered some infection
      during pregnancy but the numbers were small. CONCLUSION: Despite preventive
      strategies, working in specific jobs during pregnancy may impose a higher risk of
      infections, and working in some of these occupations may impose a slightly higher
      risk of CAs in their offspring. Most other reproductive failures were not
      increased in these occupations.

PMID- 21078153
TI  - Predictive value of procalcitonin decrease in patients with severe sepsis: a
      prospective observational study.
AB  - INTRODUCTION: This prospective study investigated the predictive value of
      procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and
      septic shock treated in intensive care. METHODS: PCT was analyzed from blood
      samples of all patients at baseline, and 155 patients 72 hours later. RESULTS:
      The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range
      (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later.
      Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with
      community-acquired infections were higher than with nosocomial infections (P =
      0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe
      sepsis with positive blood cultures was associated with higher PCT levels than
      with negative cultures (P = < 0.001). Patients with septic shock had higher PCT
      concentrations than patients without (P = 0.02). PCT concentrations did not
      differ between hospital survivors and nonsurvivors (P = 0.64 and P = 0.99,
      respectively), but mortality was lower in patients whose PCT concentration
      decreased > 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs.
      29.8%, P = 0.007). CONCLUSIONS: PCT concentrations were higher in more severe
      forms of severe sepsis, but a substantial concentration decrease was more
      important for survival than absolute values.

PMID- 21078154
TI  - Genetics of SCID.
AB  - Human SCID (Severe Combined Immunodeficiency) is a prenatal disorder of T
      lymphocyte development, that depends on the expression of numerous genes. The
      knowledge of the genetic basis of SCID is essential for diagnosis (e.g., clinical
      phenotype, lymphocyte profile) and treatment (e.g., use and type of pre
      hematopoietic stem cell transplant conditioning).Over the last years novel
      genetic defects causing SCID have been discovered, and the molecular and
      immunological mechanisms of SCID have been better characterized. Distinct forms
      of SCID show both common and peculiar (e.g., absence or presence of
      nonimmunological features) aspects, and they are currently classified into six
      groups according to prevalent pathophysiological mechanisms: impaired cytokine
      mediated signaling; pre-T cell receptor defects; increased lymphocyte apoptosis;
      defects in thymus embryogenesis; impaired calcium flux; other mechanisms.This
      review is the updated, extended and largely modified translation of the article
      "Cossu F: Le basi genetiche delle SCID", originally published in Italian language
      in the journal "Prospettive in Pediatria" 2009, 156:228-238.

PMID- 21078157
TI  - Bacteriocin synthesis in uropathogenic and commensal Escherichia coli: colicin E1
      is a potential virulence factor.
AB  - BACKGROUND: Bacteriocin production is an important characteristic of E. coli
      strains of human origin. To date, 26 colicin and 9 microcin types have been
      analyzed on a molecular level allowing molecular detection of the corresponding
      genes. The production incidence of 29 bacteriocin types and E. coli phylogroups
      were tested in a set of 361 E. coli strains isolated from human urinary tract
      infections (UTI) and in 411 control strains isolated from feces of patients
      without bacterial gut infection. RESULTS: Production of 17 and 20 individual
      bacteriocin types was found in the UTI and control strains, respectively.
      Microcin H47 encoding determinants were found more often among UTI strains
      compared to controls (37.9% and 27.0% respectively, p = 0.02) and strains
      producing microcin H47 belonged predominantly to phylogroup B2 when compared to
      other bacteriocin producers (67.4% and 36.7%, respectively; p < 0.0001).
      Producers of 3 or more identified bacteriocin types were more common in the UTI
      group (20.0% compared to 12.4% in controls, p = 0.03). In the UTI strains, there
      was a markedly higher number of those producing colicin E1 compared to controls
      (22.1% to 10.2%, respectively, p = 0.0008). Moreover, colicin E1 production was
      more common in the UTI bacteriocinogenic strains with multi-producer
      capabilities. As shown by Southern blotting, pColE1 DNA was not recognized by the
      ColIa probe and vice versa suggesting that pColE1 was independently associated
      with pColIa in UTI strains. CONCLUSION: E. coli strains isolated from human
      urinary tract infections showed increased incidence of microcin H47 and colicin
      E1 production, respectively. Moreover, colicin E1 itself appears to be a
      potentially important virulence factor of certain uropathogenic E. coli strains.

PMID- 21078158
TI  - Organised crime and the efforts to combat it: a concern for public health.
AB  - This paper considers the public health impacts of the income-generating
      activities of organised crime. These range from the traditional vice activities
      of running prostitution and supplying narcotics, to the newer growth areas of
      human trafficking in its various forms, from international supply of young people
      and children as sex workers through deceit, coercion or purchase from family,
      through to smuggling of migrants, forced labour and the theft of human tissues
      for transplant, and the sale of fake medications, foodstuffs and beverages,
      cigarettes and other counterfeit manufactures. It looks at the effect of
      globalisation on integrating supply chains from poorly-regulated and impoverished
      source regions through to their distant markets, often via disparate groups of
      organised criminals who have linked across their traditional territories for
      mutual benefit and enhanced profit, with both traditional and newly-created
      linkages between production, distribution and retail functions of cooperating
      criminal networks from different cultures. It discusses the interactions between
      criminals and the structures of the state which enable illegal and socially
      undesirable activities to proceed on a massive scale through corruption and
      subversion of regulatory mechanisms. It argues that conventional approaches to
      tackling organised crime often have deleterious consequences for public health,
      and calls for an evidence-based approach with a focus on outcomes rather than
      ideology.

PMID- 21078159
TI  - Inflammatory responses to acute pneumovirus infection in neonatal mice.
AB  - BACKGROUND: The innate immune responses of neonates differ dramatically from
      those of adults. Here we examine the acute inflammatory responses of neonatal and
      weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen
      (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of
      severe respiratory syncytial virus infection. RESULTS: We demonstrate that virus
      replication proceeds indistinguishably in all age groups (inoculated at 1, 2, 3
      and 4 weeks of age), although inflammatory responses vary in extent and
      character. Some of the biochemical mediators detected varied minimally with age
      at inoculation. Most of the mediators evaluated demonstrated elevated expression
      over baseline correlating directly with age at the time of virus inoculation.
      Among the latter group are CCL2, CCL3, and IFN-gamma, all cytokines previously
      associated with PVM-induced inflammatory pathology in mature mice. Likewise, we
      detect neutrophil recruitment to lung tissue in all age groups, but recruitment
      is most pronounced among the older (3 - 4 week old) mice. Interestingly, all mice
      exhibit failure to thrive, lagging in expected weight gain for given age,
      including the youngest mice that present little overt evidence of inflammation.
      CONCLUSIONS: Our findings among the youngest mice may explain in part the
      phenomenon of atypical or minimally symptomatic respiratory infections in human
      neonates, which may be explored further with this infection model.

PMID- 21078160
TI  - Immunostaining of modified histones defines high-level features of the human
      metaphase epigenome.
AB  - BACKGROUND: Immunolabeling of metaphase chromosome spreads can map components of
      the human epigenome at the single cell level. Previously, there has been no
      systematic attempt to explore the potential of this approach for epigenomic
      mapping and thereby to complement approaches based on chromatin
      immunoprecipitation (ChIP) and sequencing technologies. RESULTS: By
      immunostaining and immunofluorescence microscopy, we have defined the
      distribution of selected histone modifications across metaphase chromosomes from
      normal human lymphoblastoid cells and constructed immunostained karyotypes.
      Histone modifications H3K9ac, H3K27ac and H3K4me3 are all located in the same set
      of sharply defined immunofluorescent bands, corresponding to 10- to 50-Mb genomic
      segments. Primary fibroblasts gave broadly the same banding pattern. Bands co
      localize with regions relatively rich in genes and CpG islands. Staining
      intensity usually correlates with gene/CpG island content, but occasional
      exceptions suggest that other factors, such as transcription or SINE density,
      also contribute. H3K27me3, a mark associated with gene silencing, defines a set
      of bands that only occasionally overlap with gene-rich regions. Comparison of
      metaphase bands with histone modification levels across the interphase genome
      (ENCODE, ChIP-seq) shows a close correspondence for H3K4me3 and H3K27ac, but
      major differences for H3K27me3. CONCLUSIONS: At metaphase the human genome is
      packaged as chromatin in which combinations of histone modifications distinguish
      distinct regions along the euchromatic chromosome arms. These regions reflect the
      high-level interphase distributions of some histone modifications, and may be
      involved in heritability of epigenetic states, but we also find evidence for
      extensive remodeling of the epigenome at mitosis.

PMID- 21078161
TI  - Aberrant WNT/beta-catenin signaling in parathyroid carcinoma.
AB  - BACKGROUND: Parathyroid carcinoma (PC) is a very rare malignancy with a high
      tendency to recur locally, and recurrent disease is difficult to eradicate. In
      most western European countries and United States, these malignant neoplasms
      cause less than 1% of the cases with primary hyperparathyroidism, whereas
      incidence as high as 5% have been reported from Italy, Japan, and India. The
      molecular etiology of PC is poorly understood. RESULTS: The APC (adenomatous
      polyposis coli) tumor suppressor gene was inactivated by DNA methylation in five
      analyzed PCs, as determined by RT-PCR, Western blotting, and quantitative
      bisulfite pyrosequencing analyses. This was accompanied by accumulation of
      stabilized active nonphosphorylated beta-catenin, strongly suggesting aberrant
      activation of the WNT/beta-catenin signaling pathway in these tumors. Treatment
      of a primary PC cell culture with the DNA hypomethylating agent 5-aza-2'
      deoxycytidine (decitabine, Dacogen(r)) induced APC expression, reduced active
      nonphosphorylated beta-catenin, inhibited cell growth, and caused apoptosis.
      CONCLUSION: Aberrant WNT/beta-catenin signaling by lost expression and DNA
      methylation of APC, and accumulation of active nonphosphorylated beta-catenin was
      observed in the analyzed PCs. We suggest that adjuvant epigenetic therapy should
      be considered as an additional option in the treatment of patients with recurrent
      or metastatic parathyroid carcinoma.

PMID- 21078162
TI  - Out of hours care: a profile analysis of patients attending the emergency
      department and the general practitioner on call.
AB  - BACKGROUND: Overuse of emergency departments (ED) is of concern in Western
      society and it is often referred to as 'inappropriate' use. This phenomenon may
      compromise efficient use of health care personnel, infrastructure and financial
      resources of the ED. To redirect patients, an extensive knowledge of the
      experiences and attitudes of patients and their choice behaviour is necessary.
      The aim of this study is to quantify the patients and socio-economical
      determinants for choosing the general practitioner (GP) on call or the ED.
      METHODS: Data collection was conducted simultaneously in 4 large cities in
      Belgium. All patients who visited EDs or used the services of the GP on call
      during two weekends in January 2005 were enrolled in the study in a prospective
      manner. We used semi-structured questionnaires to interview patients from both
      services. RESULTS: 1611 patient contacts were suitable for further analysis. 640
      patients visited the GP and 971 went to the ED. Determinants that associated with
      the choice of the ED are: being male, having visited the ED during the past 12
      months at least once, speaking another language than Dutch or French, being of
      African (sub-Saharan as well as North African) nationality and no medical
      insurance. We also found that young men are more likely to seek help at the ED
      for minor trauma, compared to women. CONCLUSIONS: Patients tend to seek help at
      the service they are acquainted with. Two populations that distinctively seek
      help at the ED for minor medical problems are people of foreign origin and men
      suffering minor trauma. Aiming at a redirection of patients, special attention
      should go to these patients. Informing them about the health services' specific
      tasks and the needlessness of technical examinations for minor trauma, might be a
      useful intervention.

PMID- 21078163
TI  - Paradigm shift: 'ABC' to 'CAB' for cardiac arrests.
AB  - CPR has a proven role in improving survival in cardiac arrest victims, especially
      those who are outside the hospital. Guidelines published by the AHA have included
      CPR as a vital intervention for decades. The previous guidelines have focused on
      the maintenance of airway as the first step, there by delaying the provision of
      chest compressions. However, the 2010 AHA Guidelines for Cardiopulmonary
      Resuscitation and Emergency Cardiovascular Care corrects this by changing the A-B
      C of CPR to C-A-B, acknowledging that chest compressions are the most important
      aspect of the cardiac arrest management.

PMID- 21078164
TI  - Concomitant ipsilateral subcapital and intertrochanteric fractures of the femur:
      a case report.
AB  - INTRODUCTION: We report the case of an unusual combination of concomitant
      subcapital and intertrochanteric fractures of the hip in a patient after a
      motorcycle accident. To the best of our knowledge, there is no previous report in
      the literature of these conditions as a result of high energy trauma or of the
      treatment used. CASE PRESENTATION: A 36-year-old Caucasian man was admitted with
      this rare fracture combination, and was managed with closed fracture reduction
      and fixation with a dynamic hip screw combined with an anti-rotational cannulated
      screw. We found four similar cases on reviewing the literature from 1989 to 2009,
      but these were reports of older patients after low energy injury. CONCLUSION: We
      found that segmental fracture of the femoral neck region is an extremely rare and
      uncategorized hip injury that can occur not only in older people but also in
      young non-osteoporotic patients, and should be considered for inclusion in
      femoral fracture classification systems.

PMID- 21078165
TI  - Focused ultrasound-mediated bbb disruption is associated with an increase in
      activation of AKT: experimental study in rats.
AB  - BACKGROUND: The Blood Brain Barrier (BBB) maintains the homeostasis of central
      nervous system by preventing the free passage of macromolecules from the systemic
      circulation into the brain. This normal physiological function of the BBB
      presents a challenge for delivery of therapeutic compounds into the brain. Recent
      studies have shown that the application of focused ultrasound together with
      ultrasound contrast agent (microbubbles) temporarily increases the permeability
      of the BBB. This effect is associated with breakdown of tight junctions, the
      structures that regulate the paracellular permeability of the endothelial cell
      layer. The influence of this ultrasound effect on the activation of intracellular
      signaling proteins is currently not well understood. Therefore, the aim of this
      study was to investigate the activation of cell survival signaling molecules in
      response to ultrasound-mediated BBB opening; METHODS: The BBB was disrupted in
      two four-spot lines (1-1.5 mm spacing) along the right hemisphere of rat brain
      with ultrasound beams (0.3 MPa, 120 s, 10 ms bursts, repetition frequency = 1 Hz)
      in the presence Definity microbubbles. Contrast-enhanced MRI images were acquired
      to assess the extent of BBB opening upon which the animals were sacrificed and
      the brains removed and processed for biochemical and immunohistochemical
      analyses; RESULTS: Immunoblotting of sonicated brain lysates resolved by SDS-PAGE
      demonstrated an increase in phosphorylation of Akt and its downstream signaling
      molecule, GSK3beta, while the phosphorylation of MAPK remained unchanged. The
      elevated levels of pAkt and pGSK3beta are still evident after 24 hours post
      sonication, a time point where the integrity of the BBB is known to be re
      established. Furthermore, immunofluoresence staining localized this increase in
      pAkt and pGSK3beta levels to neuronal cells flanking the region of the disrupted
      BBB; CONCLUSIONS: Our data demonstrates that ultrasound-mediated BBB disruption
      causes an activation of the Akt signaling pathway in neuronal cells surrounding
      the disrupted BBB.

PMID- 21078166
TI  - Impact on fetal growth of prenatal exposure to pesticides due to agricultural
      activities: a prospective cohort study in Brittany, France.
AB  - BACKGROUND: Pesticide use is widespread in agriculture. Several studies have
      shown that pesticides used in agricultural fields can contaminate the domestic
      environment and thus be an important source of pesticide exposure of populations
      residing nearby. Epidemiological studies that have examined the health effects of
      in utero pesticide exposure from residence near agricultural activities suggest
      adverse effects, but the results are inconsistent. Our purpose was to investigate
      the effect on intrauterine growth of such exposure due to agricultural activities
      in the residential municipality. METHODS: A prospective birth cohort recruited
      3421 pregnant women in a French agricultural region (Brittany, 2002-2006) through
      gynecologists, ultrasonographers, and maternity hospitals during routine prenatal
      care visits before 19 weeks of gestation. The national agricultural census in
      2000 provided the percentages of the municipality area devoted to cultivation of
      corn, wheat, colza, peas, potatoes, and fresh vegetables. RESULTS: Birth weight
      and the risk of fetal growth restriction were not associated with agricultural
      activities in the municipality of residence in early pregnancy. Children whose
      mother lived in a municipality where peas were grown had a smaller head
      circumference at birth than those in municipalities not growing peas (-0.2 cm, p
      = 0.0002). Head circumference also tended to be lower when wheat was grown, but
      not to a statistically significant degree (p-trend = 0.10). Risk of an infant
      with a small head circumference was higher for mothers living in a municipality
      where peas (OR = 2.2; 95% CI = 1.2-3.6) or potatoes (OR = 1.5; 95% CI = 0.9-2.4)
      were grown. CONCLUSIONS: Agricultural activities in the municipality of residence
      may have negative effects on cranial growth. Cultivation of pea crops and, to a
      lesser degree, potato and wheat crops, may negatively affect head circumference.
      Insecticides, including organophosphate insecticides, were applied to most of the
      area devoted to pea and potato crops; this was less true for corn and wheat
      crops. These results must be interpreted in light of the study's limitations, in
      particular, the scale at which we could assess pesticide exposure.

PMID- 21078167
TI  - Adolescent physical activity and screen time: associations with the physical home
      environment.
AB  - BACKGROUND: Previous research on the environment and physical activity has mostly
      focused on macro-scale environments, such as the neighborhood environment. There
      has been a paucity of research on the role of micro-scale and proximal
      environments, such as that of the home which may be particularly relevant for
      younger adolescents who have more limited independence and mobility. The purpose
      of this study was to describe associations between the home environment and
      adolescent physical activity, sedentary time, and screen time. METHODS: A total
      of 613 parent-adolescent dyads were included in these analyses from two ongoing
      cohort studies. Parents completed a Physical Activity and Media Inventory (PAMI)
      of their home environment. Adolescent participants (49% male, 14.5 +/- 1.8 years)
      self-reported their participation in screen time behaviors and wore an ActiGraph
      accelerometer for one week to assess active and sedentary time. RESULTS: After
      adjusting for possible confounders, physical activity equipment density in the
      home was positively associated with accelerometer-measured physical activity (p <
      0.01) among both males and females. Most of the PAMI-derived measures of screen
      media equipment in the home were positively associated with adolescent female's
      screen time behavior (p <= 0.03). In addition, the ratio of activity to media
      equipment was positively associated with physical activity (p = 0.04) in both
      males and females and negatively associated with screen time behavior for females
      (p < 0.01). CONCLUSIONS: The home environment was associated with physical
      activity and screen time behavior in adolescents and differential environmental
      effects for males and females were observed. Additional research is warranted to
      more comprehensively assess the home environment and to identify obesogenic
      typologies of families so that early identification of at-risk families can lead
      to more informed, targeted intervention efforts.

PMID- 21078168
TI  - COX-2 activation is associated with Akt phosphorylation and poor survival in ER
      negative, HER2-positive breast cancer.
AB  - BACKGROUND: Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast
      tumors and is a target for cancer therapy. Here, we studied the association of
      COX-2 with breast cancer survival and how this association is influenced by tumor
      estrogen and HER2 receptor status and Akt pathway activation. METHODS: Tumor COX
      2, HER2 and estrogen receptor alpha (ER) expression and phosphorylation of Akt,
      BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast
      cancer. Spearman's correlation and multivariable logistic regression analyses
      were used to examine the relationship between COX-2 and tumor characteristics.
      Kaplan-Meier survival and multivariable Cox proportional hazards regression
      analyses were used to examine the relationship between COX-2 and disease-specific
      survival. RESULTS: COX-2 was significantly associated with breast cancer outcome
      in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36
      5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR
      = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with
      increased COX-2 was highest among patients who were both ER-negative and HER2
      positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER
      negative and HER2-positive tumors correlated significantly with increased
      phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at
      Ser196. CONCLUSIONS: Up-regulation of COX-2 in ER-negative and HER2-positive
      breast tumors is associated with Akt pathway activation and is a marker of poor
      outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of
      the Akt pathway may act synergistically as anticancer drugs in the ER-negative
      and HER2-positive breast cancer subtype.

PMID- 21078169
TI  - Public views of the UK media and government reaction to the 2009 swine flu
      pandemic.
AB  - BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the
      UK on 27th April 2009, after a novel virus first identified in Mexico rapidly
      evolved into a pandemic. The swine flu outbreak was the first pandemic in more
      than 40 years and for many, their first encounter with a major influenza
      outbreak. This study examines public understandings of the pandemic, exploring
      how people deciphered the threat and perceived they could control the risks.
      METHODS: Purposive sampling was used to recruit seventy three people (61 women
      and 12 men) to take part in 14 focus group discussions around the time of the
      second wave in swine flu cases. RESULTS: These discussions showed that there was
      little evidence of the public over-reacting, that people believed the threat of
      contracting swine flu was inevitable, and that they assessed their own self
      efficacy for protecting against it to be low. Respondents assessed a greater risk
      to their health from the vaccine than from the disease. Such findings could have
      led to apathy about following the UK Governments recommended health protective
      behaviours, and a sub-optimal level of vaccine uptake. More generally, people
      were confused about the difference between seasonal influenza and swine flu and
      their vaccines. CONCLUSIONS: This research suggests a gap in public
      understandings which could hinder attempts to communicate about novel flu viruses
      in the future. There was general support for the government's handling of the
      pandemic, although its public awareness campaign was deemed ineffectual as few
      people changed their current hand hygiene practices. There was less support for
      the media who were deemed to have over-reported the swine flu pandemic.

PMID- 21078170
TI  - Expression, tandem repeat copy number variation and stability of four
      macrosatellite arrays in the human genome.
AB  - BACKGROUND: Macrosatellites are some of the largest variable number tandem
      repeats in the human genome, but what role these unusual sequences perform is
      unknown. Their importance to human health is clearly demonstrated by the 4q35
      macrosatellite D4Z4 that is associated with the onset of the muscle degenerative
      disease facioscapulohumeral muscular dystrophy. Nevertheless, many other
      macrosatellite arrays in the human genome remain poorly characterized. RESULTS:
      Here we describe the organization, tandem repeat copy number variation,
      transmission stability and expression of four macrosatellite arrays in the human
      genome: the TAF11-Like array located on chromosomes 5p15.1, the SST1 arrays on
      4q28.3 and 19q13.12, the PRR20 array located on chromosome 13q21.1, and the ZAV
      array at 9q32. All are polymorphic macrosatellite arrays that at least for TAF11
      Like and SST1 show evidence of meiotic instability. With the exception of the
      SST1 array that is ubiquitously expressed, all are expressed at high levels in
      the testis and to a lesser extent in the brain. CONCLUSIONS: Our results extend
      the number of characterized macrosatellite arrays in the human genome and provide
      the foundation for formulation of hypotheses to begin assessing their functional
      role in the human genome.

PMID- 21078171
TI  - Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adults: a
      qualitative study of perspectives from professional practice.
AB  - BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) can cause
      profound and prolonged illness and disability, and poses significant problems of
      uncertainty for healthcare professionals in its diagnosis and management. The aim
      of this qualitative study was to explore the nature of professional 'best
      practice' in working with people with CFS/ME. METHODS: The views and experiences
      of health care practitioners (HCPs) were sought, who had been judged by people
      with CFS/ME themselves to have been particularly helpful and effective.
      Qualitative semi-structured interviews following a topic guide were carried out
      with six health care practitioners. Interviews were audio-recorded, transcribed
      and subject to thematic analysis. RESULTS: Five main themes were developed: 1)
      Diagnosis; 2) Professional perspectives on living with CFS/ME; 3) Interventions
      for treatment and management; 4) Professional values and support for people with
      CFS/ME and their families; 5) Health professional roles and working practices.
      Key findings related to: the diagnostic process, especially the degree of
      uncertainty which may be shared by primary care physicians and patients alike;
      the continued denial in some quarters of the existence of CFS/ME as a condition;
      the variability, complexity, and serious impact of the condition on life and
      living; the onus on the person with CFS/ME to manage their condition, supported
      by HCPs; the wealth of often conflicting and confusing information on the
      condition and options for treatment; and the vital role of extended listening and
      trustful relationships with patients. CONCLUSIONS: While professional
      frustrations were clearly expressed about the variability of services both in
      primary and specialist care and continuing equivocal attitudes to CFS/ME as a
      condition, there were also strong positive messages for people with CFS/ME where
      the right services are in place. Many of the findings from these practitioners
      seen by their patients as helping them more effectively, accord with the existing
      literature identifying the particular importance of listening skills, respect and
      trust for establishing a therapeutic relationship which recognises key features
      of the patient trajectory and promotes effective person-centred management of
      this complex condition. These findings indicate the need to build such skills and
      knowledge more systematically into professional training informed by the
      experience of specialist services and those living with the condition.

PMID- 21078173
TI  - Protective essential oil attenuates influenza virus infection: an in vitro study
      in MDCK cells.
AB  - BACKGROUND: Influenza is a significant cause of morbidity and mortality. The
      recent pandemic of a novel H1N1 influenza virus has stressed the importance of
      the search for effective treatments for this disease. Essential oils from
      aromatic plants have been used for a wide variety of applications, such as
      personal hygiene, therapeutic massage and even medical practice. In this paper,
      we investigate the potential role of an essential oil in antiviral activity.
      METHODS: We studied a commercial essential oil blend, On GuardTM, and evaluated
      its ability in modulating influenza virus, A/PR8/34 (PR8), infection in Madin
      Darby canine kidney (MDCK) cells. Influenza virus was first incubated with the
      essential oil and infectivity in MDCK cells was quantified by fluorescent focus
      assay (FFA). In order to determine the mechanism of effects of essential oil in
      viral infection inhibition, we measured hemagglutination (HA) activity, binding
      and internalization of untreated and oil-treated virus in MDCK cells by flow
      cytometry and immunofluorescence microscopy. In addition, the effect of oil
      treatment on viral transcription and translation were assayed by relative end
      point RT-PCR and western blot analysis. RESULTS: Influenza virus infectivity was
      suppressed by essential oil treatment in a dose-dependent manner; the number of
      nascent viral particles released from MDCK cells was reduced by 90% and by 40%
      when virus was treated with 1:4,000 and 1:6,000 dilutions of the oil,
      respectively. Oil treatment of the virus also decreased direct infection of the
      cells as the number of infected MDCK cells decreased by 90% and 45% when virus
      was treated with 1:2,000 and 1:3,000 dilutions of the oil, respectively. This was
      not due to a decrease in HA activity, as HA was preserved despite oil treatment.
      In addition, oil treatment did not affect virus binding or internalization in
      MDCK cells. These effects did not appear to be due to cytotoxicity of the oil as
      MDCK cell viability was only seen with concentrations of oil that were 2 to 6
      times greater than the doses that inhibited viral infectivity. RT-PCR and western
      blotting demonstrated that oil treatment of the virus inhibited viral NP and NS1
      protein, but not mRNA expression. CONCLUSIONS: An essential oil blend
      significantly attenuates influenza virus PR8 infectivity in vitro without
      affecting viral binding or cellular internalization in MDCK cells. Oil treated
      virus continued to express viral mRNAs but had minimal expression of viral
      proteins, suggesting that the antiviral effect may be due to inhibition of viral
      protein translation.

PMID- 21078172
TI  - Nutrition, environment and cardiovascular health (NESCAV): protocol of an inter
      regional cross-sectional study.
AB  - BACKGROUND: Despite the remarkable technological progress in health care and
      treatment, cardiovascular disease remains the leading cause of premature death,
      prolonged hospitalization and disability in most European countries. In the
      population of the Greater Region (Grand-Duchy of Luxembourg, Wallonia in Belgium,
      and Lorraine in France), the prevalence of cardiovascular risk factors and
      disease is among the highest in Europe, warranting the need for a better
      understanding of factors contributing to this pattern. In this context, the cross
      border "Nutrition, Environment and Cardiovascular Health-NESCAV" project is
      initiated by an inter-regional multi-disciplinary consortium and supported by the
      INTERREG IV A program "Greater Region", 2007-2013, to fight synergically and
      harmoniously against this major public health problem. METHODS/DESIGN: The
      objectives of the three-year planned project are to assess, in a representative
      sample of 3000 randomly selected individuals living at the Greater Region, 1) the
      cardiovascular health and risk profile, 2) the association between the dietary
      habits and the cardiovascular risk, 3) the association of occupational and
      environmental pollution markers with the cardiovascular risk, 4) the knowledge,
      awareness and level of control of cardiovascular risk factors, 5) the potential
      gaps in the current primary prevention, and finally, to address evidence-based
      recommendations enabling the development of inter-regional guidance to help
      policy-makers and health care workers for the prevention of cardiovascular
      disease. DISCUSSION: The findings will provide tools that may enable the Greater
      Region's decision-makers and health professionals to implement targeted and cost
      effective prevention strategies.

PMID- 21078174
TI  - Efficient parallel and out of core algorithms for constructing large bi-directed
      de Bruijn graphs.
AB  - BACKGROUND: Assembling genomic sequences from a set of overlapping reads is one
      of the most fundamental problems in computational biology. Algorithms addressing
      the assembly problem fall into two broad categories - based on the data
      structures which they employ. The first class uses an overlap/string graph and
      the second type uses a de Bruijn graph. However with the recent advances in short
      read sequencing technology, de Bruijn graph based algorithms seem to play a vital
      role in practice. Efficient algorithms for building these massive de Bruijn
      graphs are very essential in large sequencing projects based on short reads. In
      an earlier work, an O(n/p) time parallel algorithm has been given for this
      problem. Here n is the size of the input and p is the number of processors. This
      algorithm enumerates all possible bi-directed edges which can overlap with a node
      and ends up generating Theta(nSigma) messages (Sigma being the size of the
      alphabet). RESULTS: In this paper we present a Theta(n/p) time parallel algorithm
      with a communication complexity that is equal to that of parallel sorting and is
      not sensitive to Sigma. The generality of our algorithm makes it very easy to
      extend it even to the out-of-core model and in this case it has an optimal I/O
      complexity of Theta(nlog(n/B)Blog(M/B)) (M being the main memory size and B being
      the size of the disk block). We demonstrate the scalability of our parallel
      algorithm on a SGI/Altix computer. A comparison of our algorithm with the
      previous approaches reveals that our algorithm is faster--both asymptotically and
      practically. We demonstrate the scalability of our sequential out-of-core
      algorithm by comparing it with the algorithm used by VELVET to build the bi
      directed de Bruijn graph. Our experiments reveal that our algorithm can build the
      graph with a constant amount of memory, which clearly outperforms VELVET. We also
      provide efficient algorithms for the bi-directed chain compaction problem.
      CONCLUSIONS: The bi-directed de Bruijn graph is a fundamental data structure for
      any sequence assembly program based on Eulerian approach. Our algorithms for
      constructing Bi-directed de Bruijn graphs are efficient in parallel and out of
      core settings. These algorithms can be used in building large scale bi-directed
      de Bruijn graphs. Furthermore, our algorithms do not employ any all-to-all
      communications in a parallel setting and perform better than the prior
      algorithms. Finally our out-of-core algorithm is extremely memory efficient and
      can replace the existing graph construction algorithm in VELVET.

PMID- 21078175
TI  - The human G93A-SOD1 mutation in a pre-symptomatic rat model of amyotrophic
      lateral sclerosis increases the vulnerability to a mild spinal cord compression.
AB  - BACKGROUND: Traumatic injuries can undermine neurological functions and act as
      risk factors for the development of irreversible and fatal neurodegenerative
      disorders like amyotrophic lateral sclerosis (ALS). In this study, we have
      investigated how a mutation of the superoxide dismutase 1 (SOD1) gene, linked to
      the development of ALS, modifies the acute response to a gentle mechanical
      compression of the spinal cord. In a 7-day post-injury time period, we have
      performed a comparative ontological analysis of the gene expression profiles of
      injured spinal cords obtained from pre-symptomatic rats over-expressing the G93A
      SOD1 gene mutation and from wild type (WT) littermates. RESULTS: The steady post
      injury functional recovery observed in WT rats was accompanied by the early
      activation at the epicenter of injury of several growth-promoting signals and by
      the down-regulation of intermediate neurofilaments and of genes involved in the
      regulation of ion currents at the 7 day post-injury time point. The poor
      functional recovery observed in G93A-SOD1 transgenic animals was accompanied by
      the induction of fewer pro-survival signals, by an early activation of
      inflammatory markers, of several pro-apoptotic genes involved in cytochrome-C
      release and by the persistent up-regulation of the heavy neurofilament subunits
      and of genes involved in membrane excitability. These molecular changes occurred
      along with a pronounced atrophy of spinal cord motor neurones in the G93A-SOD1
      rats compared to WT littermates after compression injury. CONCLUSIONS: In an
      experimental paradigm of mild mechanical trauma which causes no major tissue
      damage, the G93A-SOD1 gene mutation alters the balance between pro-apoptotic and
      pro-survival molecular signals in the spinal cord tissue from the pre-symptomatic
      rat, leading to a premature activation of molecular pathways implicated in the
      natural development of ALS.

PMID- 21078176
TI  - Rapid induction of IgE responses to a worm cysteine protease during murine pre
      patent schistosome infection.
AB  - BACKGROUND: During the pre-patent stage of infection, juvenile Schistosoma blood
      flukes co-opt signals from the adaptive immune system to facilitate parasite
      development, but the types of responses that are induced at this early stage of
      infection, and the parasite antigens they target, have not been characterized.
      RESULTS: Through analysis of experimental pre-patent infections, we show that the
      S. mansoni cysteine protease SmCB1 is rapidly targeted by an antigen-specific IgE
      response. The induction of this response is independent of schistosome eggs as
      infection with male or female worms alone also induced SmCB1-specific IgE. We
      also show that the SmCB1-specific IgE response is dependent on cognate CD4+ T
      cell help and IL-4, suggesting that pre-patent Th2 responses provide T cell help
      for the SmCB1-specific IgE response. Finally, exposed human subjects also
      produced IgE against SmCB1. CONCLUSIONS: Our data demonstrate that, like eggs,
      schistosome worms also induce functional type 2 responses and that a parasite
      cysteine protease is an inducer of type 2 responses during the early stages of
      schistosome infection.

PMID- 21078177
TI  - Notch signaling in glioblastoma: a developmental drug target?
AB  - Malignant gliomas are among the most devastating tumors for which conventional
      therapies have not significantly improved patient outcome. Despite advances in
      imaging, surgery, chemotherapy and radiotherapy, survival is still less than 2
      years from diagnosis and more targeted therapies are urgently needed. Notch
      signaling is central to the normal and neoplastic development of the central
      nervous system, playing important roles in proliferation, differentiation,
      apoptosis and cancer stem cell regulation. Notch is also involved in the
      regulation response to hypoxia and angiogenesis, which are typical tumor and more
      specifically glioblastoma multiforme (GBM) features. Targeting Notch signaling is
      therefore a promising strategy for developing future therapies for the treatment
      of GBM. In this review we give an overview of the mechanisms of Notch signaling,
      its networking pathways in gliomas, and discuss its potential for designing novel
      therapeutic approaches.

PMID- 21078178
TI  - A factorization method for the classification of infrared spectra.
AB  - BACKGROUND: Bioinformatics data analysis often deals with additive mixtures of
      signals for which only class labels are known. Then, the overall goal is to
      estimate class related signals for data mining purposes. A convenient application
      is metabolic monitoring of patients using infrared spectroscopy. Within an
      infrared spectrum each single compound contributes quantitatively to the
      measurement. RESULTS: In this work, we propose a novel factorization technique
      for additive signal factorization that allows learning from classified samples.
      We define a composed loss function for this task and analytically derive a closed
      form equation such that training a model reduces to searching for an optimal
      threshold vector. Our experiments, carried out on synthetic and clinical data,
      show a sensitivity of up to 0.958 and specificity of up to 0.841 for a 15-class
      problem of disease classification. Using class and regression information in
      parallel, our algorithm outperforms linear SVM for training cases having many
      classes and few data. CONCLUSIONS: The presented factorization method provides a
      simple and generative model and, therefore, represents a first step towards
      predictive factorization methods.

PMID- 21078179
TI  - Clinical map document based on XML (cMDX): document architecture with mapping
      feature for reporting and analysing prostate cancer in radical prostatectomy
      specimens.
AB  - BACKGROUND: The pathology report of radical prostatectomy specimens plays an
      important role in clinical decisions and the prognostic evaluation in Prostate
      Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension
      for clinical and research purposes. To achieve electronic documentation and
      analysis, an appropriate documentation model for anatomical schemas is needed.
      For this purpose we developed cMDX. METHODS: The document architecture of cMDX
      was designed according to Open Packaging Conventions by separating the whole data
      into template data and patient data. Analogue custom XML elements were considered
      to harmonize the graphical representation (e.g. tumour extension) with the
      textual data (e.g. histological patterns). The graphical documentation was based
      on the four-layer visualization model that forms the interaction between
      different custom XML elements. Sensible personal data were encrypted with a 256
      bit cryptographic algorithm to avoid misuse. In order to assess the clinical
      value, we retrospectively analysed the tumour extension in 255 patients after
      radical prostatectomy. RESULTS: The pathology report with cMDX can represent
      pathological findings of the prostate in schematic styles. Such reports can be
      integrated into the hospital information system. "cMDX" documents can be
      converted into different data formats like text, graphics and PDF. Supplementary
      tools like cMDX Editor and an analyser tool were implemented. The graphical
      analysis of 255 prostatectomy specimens showed that PCa were mostly localized in
      the peripheral zone (Mean: 73% +/- 25). 54% of PCa showed a multifocal growth
      pattern. CONCLUSIONS: cMDX can be used for routine histopathological reporting of
      radical prostatectomy specimens and provide data for scientific analysis.

PMID- 21078180
TI  - Careers of an elite cohort of U.S. basic life science postdoctoral fellows and
      the influence of their mentor's citation record.
AB  - BACKGROUND: There is general agreement that the number of U.S. science PhDs being
      trained far exceeds the number of future academic positions. One suggested
      approach to this problem is to significantly reduce the number of PhD positions.
      A counter argument is that students are aware of the limited academic positions
      but have chosen a PhD track because it opens other, non-academic, opportunities.
      The latter view requires that students have objective information about what
      careers options will be available for them. METHODS: The scientific careers of
      the 1992-94 cohort of NIH National Institute of General Medical Sciences (NIGMS)
      Kirchstein-NRSA F32 postdoctoral fellows (PD) was determined by following their
      publications (PubMed), grants (NIH and NSF), and faculty and industry positions
      through 2009. These basic life science PDs receive support through individual
      grant applications and represent the most successful class of NIH PDs as judged
      by academic careers and grants. The sex dependence of the career and grant
      success and the influence of the PD mentor's citation record were also determined
      RESULTS: Of the 439 1992-94 NIGMS F32 fellows, the careers of 417 could be
      determined. Although females had significantly higher rates of dropping out of
      science (22% females, 9% males) there was no significant difference in the
      fraction of females that ended up as associate or full professors at research
      universities (22.8% females, 29.1% for males). More males then females ended up
      in industry (34% males, 22% females). Although there was no significant
      correlation between male grant success and their mentor's publication record (h
      index, citations, publications), there was a significant correlation for females.
      Females whose mentor's h index was in the top quartile were nearly 3 times as
      likely to receive a major grant as those whose mentors were in the bottom
      quartile (38.7% versus 13.3%). CONCLUSIONS: Sixteen years after starting their
      PD, only 9% of males had dropped out of science. More females (28%) have dropped
      out of science, primarily because fewer went into industry positions. The
      mentor's publication record does not affect the future grant success of males but
      it has a dramatic effect on female grant success.

PMID- 21078181
TI  - A tritrophic signal that attracts parasitoids to host-damaged plants withstands
      disruption by non-host herbivores.
AB  - BACKGROUND: Volatiles emitted by herbivore-infested plants are highly attractive
      to parasitoids and therefore have been proposed to be part of an indirect plant
      defense strategy. However, this proposed function of the plant-provided signals
      remains controversial, and it is unclear how specific and reliable the signals
      are under natural conditions with simultaneous feeding by multiple herbivores.
      Phloem feeders in particular are assumed to interfere with plant defense
      responses. Therefore, we investigated how attack by the piercing-sucking
      cicadellid Euscelidius variegatus influences signaling by maize plants in
      response to the chewing herbivore Spodoptera littoralis. RESULTS: The parasitoid
      Cotesia marginiventris strongly preferred volatiles of plants infested with its
      host S. littoralis. Overall, the volatile emissions induced by S. littoralis and
      E. variegatus were similar, but higher levels of certain wound-released compounds
      may have allowed the wasps to specifically recognize plants infested by hosts.
      Expression levels of defense marker genes and further behavioral bioassays with
      the parasitoid showed that neither the physiological defense responses nor the
      attractiveness of S. littoralis infested plants were altered by simultaneous E.
      variegatus attack. CONCLUSIONS: Our findings imply that plant defense responses
      to herbivory can be more robust than generally assumed and that ensuing volatiles
      convey specific information about the type of herbivore that is attacking a
      plant, even in complex situations with multiple herbivores. Hence, the results of
      this study support the notion that herbivore-induced plant volatiles may be part
      of a plant's indirect defense stratagem.

PMID- 21078182
TI  - An improved method for scoring protein-protein interactions using semantic
      similarity within the gene ontology.
AB  - BACKGROUND: Semantic similarity measures are useful to assess the physiological
      relevance of protein-protein interactions (PPIs). They quantify similarity
      between proteins based on their function using annotation systems like the Gene
      Ontology (GO). Proteins that interact in the cell are likely to be in similar
      locations or involved in similar biological processes compared to proteins that
      do not interact. Thus the more semantically similar the gene function annotations
      are among the interacting proteins, more likely the interaction is
      physiologically relevant. However, most semantic similarity measures used for PPI
      confidence assessment do not consider the unequal depth of term hierarchies in
      different classes of cellular location, molecular function, and biological
      process ontologies of GO and thus may over-or under-estimate similarity. RESULTS:
      We describe an improved algorithm, Topological Clustering Semantic Similarity
      (TCSS), to compute semantic similarity between GO terms annotated to proteins in
      interaction datasets. Our algorithm, considers unequal depth of biological
      knowledge representation in different branches of the GO graph. The central idea
      is to divide the GO graph into sub-graphs and score PPIs higher if participating
      proteins belong to the same sub-graph as compared to if they belong to different
      sub-graphs. CONCLUSIONS: The TCSS algorithm performs better than other semantic
      similarity measurement techniques that we evaluated in terms of their performance
      on distinguishing true from false protein interactions, and correlation with gene
      expression and protein families. We show an average improvement of 4.6 times the
      F1 score over Resnik, the next best method, on our Saccharomyces cerevisiae PPI
      dataset and 2 times on our Homo sapiens PPI dataset using cellular component,
      biological process and molecular function GO annotations.

PMID- 21078183
TI  - Association of residential dampness and mold with respiratory tract infections
      and bronchitis: a meta-analysis.
AB  - BACKGROUND: Dampness and mold have been shown in qualitative reviews to be
      associated with a variety of adverse respiratory health effects, including
      respiratory tract infections. Several published meta-analyses have provided
      quantitative summaries for some of these associations, but not for respiratory
      infections. Demonstrating a causal relationship between dampness-related agents,
      which are preventable exposures, and respiratory tract infections would suggest
      important new public health strategies. We report the results of quantitative
      meta-analyses of published studies that examined the association of dampness or
      mold in homes with respiratory infections and bronchitis. METHODS: For primary
      studies meeting eligibility criteria, we transformed reported odds ratios (ORs)
      and confidence intervals (CIs) to the log scale. Both fixed and random effects
      models were applied to the log ORs and their variances. Most studies contained
      multiple estimated ORs. Models accounted for the correlation between multiple
      results within the studies analyzed. One set of analyses was performed with all
      eligible studies, and another set restricted to studies that controlled for age,
      gender, smoking, and socioeconomic status. Subgroups of studies were assessed to
      explore heterogeneity. Funnel plots were used to assess publication bias.
      RESULTS: The resulting summary estimates of ORs from random effects models based
      on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all
      cases. Use of different analysis models and restricting analyses based on control
      of multiple confounding variables changed findings only slightly. ORs (95% CIs)
      from random effects models using studies adjusting for major confounding
      variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections,
      1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper
      respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in
      children or infants, 1.48 (1.33-1.65). Little effect of publication bias was
      evident. Estimated attributable risk proportions ranged from 8% to 20%.
      CONCLUSIONS: Residential dampness and mold are associated with substantial and
      statistically significant increases in both respiratory infections and
      bronchitis. If these associations were confirmed as causal, effective control of
      dampness and mold in buildings would prevent a substantial proportion of
      respiratory infections.

PMID- 21078184
TI  - A genomic approach highlights common and diverse effects and determinants of
      susceptibility on the yeast Saccharomyces cerevisiae exposed to distinct
      antimicrobial peptides.
AB  - BACKGROUND: The mechanism of action of antimicrobial peptides (AMP) was initially
      correlated with peptide membrane permeation properties. However, recent evidences
      indicate that action of a number of AMP is more complex and involves specific
      interactions at cell envelopes or with intracellular targets. In this study, a
      genomic approach was undertaken on the model yeast Saccharomyces cerevisiae to
      characterize the antifungal effect of two unrelated AMP. RESULTS: Two
      differentiated peptides were used: the synthetic cell-penetrating PAF26 and the
      natural cytolytic melittin. Transcriptomic analyses demonstrated distinctive gene
      expression changes for each peptide. Quantitative RT-PCR confirmed differential
      expression of selected genes. Gene Ontology (GO) annotation of differential gene
      lists showed that the unique significant terms shared by treatment with both
      peptides were related to the cell wall (CW). Assays with mutants lacking CW
      related genes including those of MAPK signaling pathways revealed genes having
      influence on sensitivity to peptides. Fluorescence microscopy and flow cytometry
      demonstrated PAF26 interaction with cells and internalization that correlated
      with cell killing in sensitive CW-defective mutants such as Deltaecm33 or
      Deltassd1. GO annotation also showed differential responses between peptides,
      which included ribosomal biogenesis, ARG genes from the metabolism of amino
      groups (specifically induced by PAF26), or the reaction to unfolded protein
      stress. Susceptibility of deletion mutants confirmed the involvement of these
      processes. Specifically, mutants lacking ARG genes from the metabolism of
      arginine pathway were markedly more resistant to PAF26 and had a functional CW.
      In the deletant in the arginosuccinate synthetase (ARG1) gene, PAF26 interaction
      occurred normally, thus uncoupling peptide interaction from cell killing. The
      previously described involvement of the glycosphingolipid gene IPT1 was extended
      to the peptides studied here. CONCLUSIONS: Reinforcement of CW is a general
      response common after exposure to distinct AMP, and likely contributes to shield
      cells from peptide interaction. However, a weakened CW is not necessarily
      indicative of a higher sensitivity to AMP. Additional processes modulate
      susceptibility to specific peptides, exemplified in the involvement of the
      metabolism of amino groups in the case of PAF26. The relevance of the response to
      unfolded protein stress or the sphingolipid biosynthesis, previously reported for
      other unrelated AMP, was also independently confirmed.

PMID- 21078186
TI  - Assessing karyotype precision by microarray-based comparative genomic
      hybridization in the myelodysplastic/myeloproliferative syndromes.
AB  - BACKGROUND: Recent genome-wide microarray-based research investigations have
      revealed a high frequency of submicroscopic copy number alterations (CNAs) in the
      myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic
      hybridization (aCGH) has the potential to detect new clinically relevant genomic
      markers in a diagnostic laboratory. RESULTS: We performed an exploratory study on
      30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid
      leukemia (AML) (% bone marrow blasts <= 30%, range 0-30%, median, 8%) by aCGH,
      using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample
      data were compared to corresponding cytogenetics, fluorescence in situ
      hybridization (FISH), and clinical-pathological findings. Previously unidentified
      imbalances, in particular those considered submicroscopic aberrations (< 10 Mb),
      were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the
      cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new
      CNAs in 14/30 (47%) patients, including 28 submicroscopic or hidden aberrations
      verified by FISH studies. Cryptic 344-kb RUNX1 deletions were found in three
      patients at time of AML transformation. Other hidden CNAs involved 3q26.2/EVI1,
      5q22/APC, 5q32/TCERG1,12p13.1/EMP1, 12q21.3/KITLG, and 17q11.2/NF1. Gains of
      CCND2/12p13.32 were detected in two patients. aCGH failed to detect a balanced
      translocation (n = 1) and low-level clonality (n = 4) in five karyotypically
      aberrant samples, revealing clinically important assay limitations. CONCLUSIONS:
      The detection of previously known and unknown genomic alterations suggests that
      aCGH has considerable promise for identification of both recurring microscopic
      and submicroscopic genomic imbalances that contribute to myeloid disease
      pathogenesis and progression. These findings suggest that development of higher
      resolution microarray platforms could improve karyotyping in clinical practice.

PMID- 21078185
TI  - Functional analysis of the Theobroma cacao NPR1 gene in Arabidopsis.
AB  - BACKGROUND: The Arabidopsis thaliana NPR1 gene encodes a transcription
      coactivator (NPR1) that plays a major role in the mechanisms regulating plant
      defense response. After pathogen infection and in response to salicylic acid (SA)
      accumulation, NPR1 translocates from the cytoplasm into the nucleus where it
      interacts with other transcription factors resulting in increased expression of
      over 2000 plant defense genes contributing to a pathogen resistance response.
      RESULTS: A putative Theobroma cacao NPR1 cDNA was isolated by RT-PCR using
      degenerate primers based on homologous sequences from Brassica, Arabidopsis and
      Carica papaya. The cDNA was used to isolate a genomic clone from Theobroma cacao
      containing a putative TcNPR1 gene. DNA sequencing revealed the presence of a 4.5
      kb coding region containing three introns and encoding a polypeptide of 591 amino
      acids. The predicted TcNPR1 protein shares 55% identity and 78% similarity to
      Arabidopsis NPR1, and contains each of the highly conserved functional domains
      indicative of this class of transcription factors (BTB/POZ and ankyrin repeat
      protein-protein interaction domains and a nuclear localization sequence (NLS)).
      To functionally define the TcNPR1 gene, we transferred TcNPR1 into an Arabidopsis
      npr1 mutant that is highly susceptible to infection by the plant pathogen
      Pseudomonas syringae pv. tomato DC3000. Driven by the constitutive CaMV35S
      promoter, the cacao TcNPR1 gene partially complemented the npr1 mutation in
      transgenic Arabidopsis plants, resulting in 100 fold less bacterial growth in a
      leaf infection assay. Upon induction with SA, TcNPR1 was shown to translocate
      into the nucleus of leaf and root cells in a manner identical to Arabidopsis
      NPR1. Cacao NPR1 was also capable of participating in SA-JA signaling crosstalk,
      as evidenced by the suppression of JA responsive gene expression in TcNPR1
      overexpressing transgenic plants. CONCLUSION: Our data indicate that the TcNPR1
      is a functional ortholog of Arabidopsis NPR1, and is likely to play a major role
      in defense response in cacao. This fundamental knowledge can contribute to
      breeding of disease resistant cacao varieties through the application of
      molecular markers or the use of transgenic strategies.

PMID- 21078187
TI  - Norwegian GPs' participation in multidisciplinary meetings: a register-based
      study from 2007.
AB  - BACKGROUND: An increasing number of patients with chronic disorders and a more
      complex health service demand greater interdisciplinary collaboration in Primary
      Health Care. The aim of this study was therefore to identify factors related to
      general practitioners (GPs), their list populations and practice municipalities
      associated with a high rate of GP participation in multidisciplinary meetings
      (MDMs). METHODS: A national cross-sectional register-based study of Norwegian
      general practice was conducted, including data on all GPs in the Regular GP
      Scheme in 2007 (N = 3179). GPs were grouped into quartiles based on the annual
      number of MDMs per patient on their list, and the groups were compared using one
      way analysis of variance. Binary logistic regression was used to analyse
      associations between high rates of participation and characteristics of the GP,
      their list population and practice municipality. RESULTS: On average, GPs
      attended 30 MDMs per year. The majority of the meetings concerned patients in the
      age groups 20-59 years. Psychological disorders were the motivation for 53% of
      the meetings. In a multivariate logistic regression model, the following
      characteristics predicted a high rate of MDM attendance: younger age of the GP,
      with an OR of 1.6 (95% CI 1.2-2.1) for GPs < 45 years, a short patient list, with
      an OR of 4.9 (3.2-7.5) for list sizes below 800 compared to lists >= 1600, higher
      proportion of psychological diagnosis in consultations (OR3.4 (2.6-4.4)) and a
      high MDM proportion with elderly patients (OR 4.1 (3.3-5.4)). Practising in
      municipalities with less than 10,000 inhabitants (OR 3.7 (2.8-4.9)) and a high
      proportion of disability pensioners (OR 1.6 (1.2-2.2)) or patients receiving
      social assistance (OR 2.2 (1.7-2.8)) also predicted high rates of meetings.
      CONCLUSIONS: Psychological problems including substance addiction gave grounds
      for the majority of MDMs. GPs with a high proportion of consultations with such
      problems also participated more frequently in MDMs. List size was negatively
      associated with the rate of MDMs, while a more disadvantaged list population was
      positively associated. Working in smaller organisational units seemed to
      facilitate cooperation between different professionals. There may be a generation
      shift towards more frequent participation in interdisciplinary work among younger
      GPs.

PMID- 21078190
TI  - Deaths of cyclists in London: trends from 1992 to 2006.
AB  - BACKGROUND: Cycling is an increasingly important mode of transport for
      environmental and health reasons. Cycling fatalities in London were previously
      investigated in 1994 using routinely collected data. Since then, there have been
      shifts in the modes of transport used, and in transport policies. We sought to
      replicate the previous work using data on cyclist deaths in London between 1992
      and 2006, specifically investigating whether heavy goods vehicles continued to
      pose a threat. METHODS: Observational study based on analysis of time series of
      police road casualties data, 1992 to 2006, in London, UK. The main outcome
      measures were cyclists killed in road traffic collisions. Poisson regression and
      chi-squared test for homogeneity were used to assess time effects. Travel flow
      data was then used to estimate annual fatality rates per 100,000 cyclists per
      kilometre. RESULTS: From 1992 to 2006 there was a mean of 16 cycling fatalities
      per year (range 8-21). 146 deaths (60%) were in inner London and 96 in outer
      London. There was no evidence for a decline over time (p = 0.7) other than a
      pronounced dip in 2004 when there were 8 fatalities. Freight vehicles were
      involved in 103 of 242 (43%) of all incidents and the vehicle was making a left
      turn in over half of these (53%). The fatality rate ranged from 20.5 deaths in
      1992 to 11.1 deaths in 2006 per 100,000 estimated cyclists per kilometre (rate
      ratio 0.54, 95% confidence interval 0.28 to 1.03). CONCLUSIONS: There is little
      evidence fatality rates have fallen. Freight vehicles over 3.5 tonnes continue to
      present a disproportionate threat; they should be removed from urban roads and
      more appropriate means of delivery of essential goods found.

PMID- 21078188
TI  - Targeting of highly conserved Dengue virus sequences with anti-Dengue virus trans
      splicing group I introns.
AB  - BACKGROUND: Dengue viruses (DENV) are one of the most important viral diseases in
      the world with approximately 100 million infections and 200,000 deaths each year.
      The current lack of an approved tetravalent vaccine and ineffective insecticide
      control measures warrant a search for alternatives to effectively combat DENV.
      The trans-splicing variant of the Tetrahymena thermophila group I intron
      catalytic RNA, or ribozyme, is a powerful tool for post-transcriptional RNA
      modification. The nature of the ribozyme and the predictability with which it can
      be directed makes it a powerful tool for modifying RNA in nearly any cell type
      without the need for genome-altering gene therapy techniques or dependence on
      native cofactors. RESULTS: Several anti-DENV Group I trans-splicing introns
      (alphaDENV-GrpIs) were designed and tested for their ability to target DENV-2 NGC
      genomes in situ. We have successfully targeted two different uracil bases on the
      positive sense genomic strand within the highly conserved 5'-3' cyclization
      sequence (CS) region common to all serotypes of DENV with our alphaDENV-GrpIs.
      Our ribozymes have demonstrated ability to specifically trans-splice a new RNA
      sequence downstream of the targeted site in vitro and in transfected insect cells
      as analyzed by firefly luciferase and RT-PCR assays. The effectiveness of these
      alphaDENV-GrpIs to target infecting DENV genomes is also validated in transfected
      or transformed Aedes mosquito cell lines upon infection with unattenuated DENV-2
      NGC. CONCLUSIONS: Analysis shows that our alphaDENV-GrpIs have the ability to
      effectively trans-splice the DENV genome in situ. Notably, these results show
      that the alphaDENV-GrpI 9v1, designed to be active against all forms of Dengue
      virus, effectively targeted the DENV-2 NGC genome in a sequence specific manner.
      These novel alphaDENV-GrpI introns provide a striking alternative to other RNA
      based approaches for the transgenic suppression of DENV in transformed mosquito
      cells and tissues.

PMID- 21078189
TI  - Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced
      under hypoxia and is independent of p53 and p21.
AB  - INTRODUCTION: We have shown that the radio sensitizer DCQ enhances sensitivity of
      HCT116 human colon cancer cells to hypoxia. However, it is not known whether the
      p53 or p21 genes influence cellular response to DCQ. In this study, we used
      HCT116 that are either wildtype for p53 and p21, null for p53 or null for p21 to
      understand the role of these genes in DCQ toxicity. METHODS: HCT116 cells were
      exposed to DCQ and incubated under normoxia or hypoxia and the viability, colony
      forming ability, DNA damage and apoptotic responses of these cells was
      determined, in addition to the modulation of HIF-1alpha and of p53, p21, caspase
      2, and of the ataxia telangiectasia mutated (ATM) target PIDD-C. RESULTS: DCQ
      decreased colony forming ability and viability of all HCT116 cells to a greater
      extent under hypoxia than normoxia and the p21-/-cell line was most sensitive.
      Cells had different HIF-1alpha responses to hypoxia and/or drug treatment. In
      p53+/+, DCQ significantly inhibited the hypoxia-induced increases in HIF-1alpha
      protein, in contrast to the absence of a significant HIF-1alpha increase or
      modulation by DCQ in p21-/- cells. In p53-/- cells, 10 MUM DCQ significantly
      reduced HIF-1alpha expression, especially under hypoxia, despite the constitutive
      expression of this protein in control cells. Higher DCQ doses induced PreG1-phase
      increase and apoptosis, however, lower doses caused mitotic catastrophe. In
      p53+/+ cells, apoptosis correlated with the increased expression of the pro
      apoptotic caspase-2 and inhibition of the pro-survival protein PIDD-C. Exposure
      of p53+/+ cells to DCQ induced single strand breaks and triggered the activation
      of the nuclear kinase ATM by phosphorylation at Ser-1981 in all cell cycle
      phases. On the other hand, no drug toxicity to normal FHs74 Int human intestinal
      cell line was observed. CONCLUSIONS: Collectively, our findings indicate that DCQ
      reduces the colony survival of HCT116 and induces apoptosis even in cells that
      are null for p53 or p21, which makes it a molecule of clinical significance,
      since many resistant colon tumors harbor mutations in p53.

PMID- 21078191
TI  - Abdominal obesity and other risk factors largely explain the high CRP in
      indigenous Australians relative to the general population, but not gender
      differences: a cross-sectional study.
AB  - BACKGROUND: Previous studies reported high C-reactive protein (CRP) levels in
      Indigenous Australians, which may contribute to their high risk of cardiovascular
      disease. We compared CRP levels in Indigenous Australians and the general
      population, accounting for obesity and other risk factors. METHODS: Cross
      sectional study of CRP and risk factors (weight, height, waist and hip
      circumferences, blood pressure, lipids, blood glucose, and smoking status) in
      population-based samples from the Diabetes and Related conditions in Urban
      Indigenous people in the Darwin region (DRUID) study, and the Australian
      Diabetes, Obesity and Lifestyle study (AusDiab) follow-up. RESULTS: CRP
      concentrations were higher in women than men and in DRUID than AusDiab. After
      multivariate adjustment, including waist circumference, the odds of high CRP
      (>3.0 mg/L) in DRUID relative to AusDiab were no longer statistically
      significant, but elevated CRP was still more likely in women than men. After
      adjusting for BMI (instead of waist circumference) the odds for elevated CRP in
      DRUID participants were still higher relative to AusDiab participants among
      women, but not men. Lower HDL cholesterol, impaired glucose tolerance (IGT), and
      higher diastolic blood pressure were associated with having a high CRP in both
      men and women, while current smoking was associated with high CRP in men but not
      women. CONCLUSIONS: High concentrations of CRP in Indigenous participants were
      largely explained by other risk factors, in particular abdominal obesity.
      Irrespective of its independence as a risk factor, or its aetiological
      association with coronary heart disease (CHD), the high CRP levels in urban
      Indigenous women are likely to reflect increased vascular and metabolic risk. The
      significance of elevated CRP in Indigenous Australians should be investigated in
      future longitudinal studies.

PMID- 21078192
TI  - TESTLoc: protein subcellular localization prediction from EST data.
AB  - BACKGROUND: The eukaryotic cell has an intricate architecture with compartments
      and substructures dedicated to particular biological processes. Knowing the
      subcellular location of proteins not only indicates how bio-processes are
      organized in different cellular compartments, but also contributes to unravelling
      the function of individual proteins. Computational localization prediction is
      possible based on sequence information alone, and has been successfully applied
      to proteins from virtually all subcellular compartments and all domains of life.
      However, we realized that current prediction tools do not perform well on partial
      protein sequences such as those inferred from Expressed Sequence Tag (EST) data,
      limiting the exploitation of the large and taxonomically most comprehensive body
      of sequence information from eukaryotes. RESULTS: We developed a new predictor,
      TESTLoc, suited for subcellular localization prediction of proteins based on
      their partial sequence conceptually translated from ESTs (EST-peptides). Support
      Vector Machine (SVM) is used as computational method and EST-peptides are
      represented by different features such as amino acid composition and
      physicochemical properties. When TESTLoc was applied to the most challenging test
      case (plant data), it yielded high accuracy (~85%). CONCLUSIONS: TESTLoc is a
      localization prediction tool tailored for EST data. It provides a variety of
      models for the users to choose from, and is available for download at
      http://megasun.bch.umontreal.ca/~shenyq/TESTLoc/TESTLoc.html.

PMID- 21078193
TI  - An in silico analysis of the mitochondrial protein import apparatus of plants.
AB  - BACKGROUND: An in silico analysis of the mitochondrial protein import apparatus
      from a variety of species; including Chlamydomonas reinhardtii, Chlorella
      variabilis, Ectocarpus siliculosus, Cyanidioschyzon merolae, Physcomitrella
      patens, Selaginella moellendorffii, Picea glauca, Oryza sativa and Arabidopsis
      thaliana was undertaken to determine if components differed within and between
      plant and non-plant species. RESULTS: The channel forming subunits of the outer
      membrane components Tom40 and Sam50 are conserved between plant groups and other
      eukaryotes. In contrast, the receptor component(s) in green plants, particularly
      Tom20, (C. reinhardtii, C. variabilis, P. patens, S. moellendorffii, P. glauca,
      O. sativa and A. thaliana) are specific to this lineage. Red algae contain a
      Tom22 receptor that is orthologous to yeast Tom22. Furthermore, plant
      mitochondrial receptors display differences between various plant lineages. These
      are evidenced by distinctive motifs in all plant Metaxins, which are absent in
      red algae, and the presence of the outer membrane receptor OM64 in Angiosperms
      (rice and Arabidopsis), but not in lycophytes (S. moellendorffii) and gymnosperms
      (P. glauca). Furthermore, although the intermembrane space receptor Mia40 is
      conserved across a wide phylogenetic range, its function differs between
      lineages. In all plant lineages, Tim17 contains a C-terminal extension, which may
      act as a receptor component for the import of nucleic acids into plant
      mitochondria. CONCLUSIONS: It is proposed that the observed functional
      divergences are due to the selective pressure to sort proteins between
      mitochondria and chloroplasts, resulting in differences in protein receptor
      components between plant groups and other organisms. Additionally, diversity of
      receptor components is observed within the plant kingdom. Even when receptor
      components are orthologous across plant and non-plant species, it appears that
      the functions of these have expanded or diverged in a lineage specific manner.

PMID- 21078194
TI  - Acupuncture for dry eye: a multicentre randomised controlled trial with active
      comparison intervention (artificial tear drop) using a mixed method approach
      protocol.
AB  - BACKGROUND: Previous studies of acupuncture show favourable results for both
      subjective and objective outcomes of dry eye. However, firm conclusions could not
      be drawn from these studies because the quality of the trials was too low to
      establish concrete evidence. Therefore, this study was designed both to avoid the
      flaws of the existing trials and to assess the effectiveness, cost-effectiveness
      and qualitative characteristics of acupuncture treatment for dry eye.
      METHODS/DESIGN: One hundred fifty participants with dry eye will be recruited
      into three independent hospitals from different areas: Korea Institute of
      Oriental Medicine, DongGuk University Ilsan Oriental Hospital and Dongshin
      University Gwangju Oriental Hospital. The number of participants required was
      calculated from the data of a previous, relevant study. These patients will be
      randomly allocated into acupuncture treatment or artificial tear groups. Either
      17 acupuncture points (bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, LI11 and
      single GV23) will be used 3 times a week or disposable artificial tear drops
      (Refresh Plus(r), ALLERGAN) will be provided for use at least once a day for 4
      weeks. The ocular surface disease index (OSDI), tear film break-up time (TFBUT),
      Schirmer I test, visual analogue scale (VAS) for self-assessment of ocular
      discomfort, general assessment (by both acupuncture practitioners and
      participants) and quality of life (QOL) through the Measure Yourself Medical
      Outcome Profile-2 (MYMOP-2) will be assessed for approximately 3-months for each
      study participant. In addition, qualitative study and cost-effectiveness of
      acupuncture treatment will be conducted. TRIAL REGISTRATION: ClinicalTrials.gov
      (Identifier: NCT01105221).

PMID- 21078195
TI  - Reconstruction of epidemic curves for pandemic influenza A (H1N1) 2009 at city
      and sub-city levels.
AB  - To better describe the epidemiology of influenza at local level, the time course
      of pandemic influenza A (H1N1) 2009 in the city of Hong Kong was reconstructed
      from notification data after decomposition procedure and time series analysis.
      GIS (geographic information system) methodology was incorporated for assessing
      spatial variation. Between May and September 2009, a total of 24415 cases were
      successfully geocoded, out of 25473 (95.8%) reports in the original dataset. The
      reconstructed epidemic curve was characterized by a small initial peak, a nadir
      followed by rapid rise to the ultimate plateau. The full course of the epidemic
      had lasted for about 6 months. Despite the small geographic area of only 1000
      Km2, distinctive spatial variation was observed in the configuration of the
      curves across 6 geographic regions. With the relatively uniform physical and
      climatic environment within Hong Kong, the temporo-spatial variability of
      influenza spread could only be explained by the heterogeneous population
      structure and mobility patterns. Our study illustrated how an epidemic curve
      could be reconstructed using regularly collected surveillance data, which would
      be useful in informing intervention at local levels.

PMID- 21078196
TI  - Protocol for a randomised controlled trial of risk screening and early
      intervention comparing child- and family-focused cognitive-behavioural therapy
      for PTSD in children following accidental injury.
AB  - BACKGROUND: Accidental injury represents the most common type of traumatic event
      to which a child or adolescent may be exposed, with a significant number of these
      children going on to experience posttraumatic stress disorder (PTSD). However,
      very little research has examined potential interventions for the treatment of
      PTSD in these children. The present trial aims to evaluate and compare child- and
      family-focused versions of a cognitive-behavioural early intervention for PTSD
      following accidental injury. METHODS/DESIGN: The principal clinical question
      under investigation is the efficacy of an early, trauma-focused cognitive
      behavioural intervention for the treatment of PTSD in children following
      accidental injury. Specifically, we compare the efficacy of two active treatments
      (child-focused and family-focused CBT) and a waitlist control (no therapy) to
      determine which is associated with greater reductions in psychological and health
      related outcome measures over time. The primary outcome will be a reduction in
      trauma symptoms on a diagnostic interview in the active treatments compared to
      the waitlist control and greater reductions in the family-compared to the child
      focused condition. In doing so, this project will also trial a method of stepped
      screening and assessment to determine those children requiring early intervention
      for PTSD following accidental injury. DISCUSSION: The present trial will be one
      of the first controlled trials to examine a trauma-focused CBT, early
      intervention for children experiencing PTSD following accidental injury (as
      opposed to other types of traumatic events) and the first within a stepped care
      approach. In addition, it will provide the first evidence comparing the efficacy
      of child and family-focused interventions for this target group. Given the
      significant number of children and adolescents exposed to accidental injury, the
      successful implementation of this protocol has considerable implications. If
      efficacious, this early intervention will assist in reducing symptoms of
      traumatic stress as well as preventing chronic disorder and disability in
      children experiencing acute PTSD following accidental injury. TRIAL REGISTRATION:
      Controlled-trials.com: ISRCTN79049138.

PMID- 21078197
TI  - Clinical research evidence of cupping therapy in China: a systematic literature
      review.
AB  - BACKGROUND: Though cupping therapy has been used in China for thousands of years,
      there has been no systematic summary of clinical research on it.This review is to
      evaluate the therapeutic effect of cupping therapy using evidence-based approach
      based on all available clinical studies. METHODS: We included all clinical
      studies on cupping therapy for all kinds of diseases. We searched six electronic
      databases, all searches ended in December 2008. We extracted data on the type of
      cupping and type of diseases treated. RESULTS: 550 clinical studies were
      identified published between 1959 and 2008, including 73 randomized controlled
      trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case
      reports. Number of RCTs obviously increased during past decades, but the quality
      of the RCTs was generally poor according to the risk of bias of the Cochrane
      standard for important outcome within each trials. The diseases in which cupping
      was commonly employed included pain conditions, herpes zoster, cough or asthma,
      etc. Wet cupping was used in majority studies, followed by retained cupping,
      moving cupping, medicinal cupping, etc. 38 studies used combination of two types
      of cupping therapies. No serious adverse effects were reported in the studies.
      CONCLUSIONS: According to the above results, quality and quantity of RCTs on
      cupping therapy appears to be improved during the past 50 years in China, and
      majority of studies show potential benefit on pain conditions, herpes zoster and
      other diseases. However, further rigorous designed trials in relevant conditions
      are warranted to support their use in practice.

PMID- 21078198
TI  - Constructing the HBV-human protein interaction network to understand the
      relationship between HBV and hepatocellular carcinoma.
AB  - BACKGROUND: Epidemiological studies have clearly validated the association
      between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).
      Patients with chronic HBV infection are at increased risk of HCC, in particular
      those with active liver disease and cirrhosis. METHODS: We catalogued all
      published interactions between HBV and human proteins, identifying 250
      descriptions of HBV and human protein interactions and 146 unique human proteins
      that interact with HBV proteins by text mining. RESULTS: Integration of this data
      set into a reconstructed human interactome showed that cellular proteins
      interacting with HBV are made up of core proteins that are interconnected with
      many pathways. A global analysis based on functional annotation highlighted the
      enrichment of cellular pathways targeted by HBV. CONCLUSIONS: By connecting the
      cellular proteins targeted by HBV, we have constructed a central network of
      proteins associated with hepatocellular carcinoma, which might be to regard as
      the basis of a detailed map for tracking new cellular interactions, and guiding
      future investigations.

PMID- 21078199
TI  - Identification of 5 novel germline APC mutations and characterization of clinical
      phenotypes in Japanese patients with classical and attenuated familial
      adenomatous polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant
      hereditary disease characterized by multiple colorectal adenomatous polyps and
      frequent extracolonic manifestations. An attenuated form of FAP (AFAP) is
      diagnosed based on a milder colorectal phenotype, and the colorectal phenotype of
      (A)FAP has been linked to germline APC mutations. The relationships between the
      spectrum of mutations and extracolonic manifestations are quite well known, but
      they need to be further defined. FINDINGS: Nine germline APC mutations, but no
      large deletions, were identified in the APC locus of 8 (A)FAP patients, and 5 of
      the mutations, c.446A > T (p.Asp149Val), c.448A > T (p.Lys150X), c.454_457insAGAA
      (p.Glu152ArgfsX17), c.497insA (p.Thr166AsnfsX2), and c.1958G > C (p.Arg653Ser),
      were novel mutations. In one patient the p.Asp149Val mutation and p.Lys150X
      mutation were detected in the same APC allele. The c.1958G > C mutation was
      located in the last nucleotide of exon 14, and RT-PCR analysis revealed that the
      mutation resulted in abnormal splicing. The above findings meant that a nonsense
      mutation, a frameshift mutation, or an exonic mutation leading to abnormal
      splicing was found in every patient. The following phenotypes, especially
      extracolonic manifestations, were observed in our (A)FAP patients: (1) multiple
      gastroduodenal adenomas and early-onset gastric carcinoma in AFAP patients with
      an exon 4 mutation; (2) a desmoid tumor in two FAP patients with a germline APC
      mutation outside the region between codons 1403 and 1578, which was previously
      reported to be associated with the development of desmoid tumors in FAP patients;
      (3) multiple myeloma in an AFAP patient with an exon 4 mutation. CONCLUSIONS:
      Nine germline APC mutations, 5 of them were novel, were identified in 8 Japanese
      (A)FAP patients, and some associations between germline APC mutations and
      extracolonic manifestations were demonstrated. These findings should contribute
      to establishing relationships between germline APC mutations and the extracolonic
      manifestations of (A)FAP patients in the future.

PMID- 21078200
TI  - The SHED-IT community trial study protocol: a randomised controlled trial of
      weight loss programs for overweight and obese men.
AB  - BACKGROUND: Obesity is a major cause of preventable death in Australia with
      prevalence increasing at an alarming rate. Of particular concern is that
      approximately 68% of men are overweight/obese, yet are notoriously difficult to
      engage in weight loss programs, despite being more susceptible than women to
      adverse weight-related outcomes. There is a need to develop and evaluate obesity
      treatment programs that target and appeal to men. The primary aim of this study
      is to evaluate the efficacy of two relatively low intensity weight loss programs
      developed specifically for men. METHODS AND DESIGN: The study design is an
      assessor blinded, parallel-group randomised controlled trial that recruited 159
      overweight and obese men in Newcastle, Australia. Inclusion criteria included:
      BMI 25-40 (kg/m2); no participation in other weight loss programs during the
      study; pass a health-screening questionnaire and pre-exercise risk assessment;
      available for assessment sessions; access to a computer with e-mail and Internet
      facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help,
      Exercise and Diet using Internet Technology) study via the media and emails sent
      to male dominated workplaces. Men were stratified by BMI category (overweight,
      obese class I, obese class II) and randomised to one of three groups: (1) SHED-IT
      Resources - provision of materials (DVD, handbooks, pedometer, tape measure) with
      embedded behaviour change strategies to support weight loss; (2) SHED-IT Online -
      same materials as SHED-IT Resources plus access to and instruction on how to use
      the study website; (3) Wait-list Control. The intervention programs are three
      months long with outcome measures taken by assessors blinded to group allocation
      at baseline, and 3- and 6-months post baseline. Outcome measures include: weight
      (primary outcome), % body fat, waist circumference, blood pressure, resting heart
      rate, objectively measured physical activity, self-reported dietary intake,
      sedentary behaviour, physical activity and dietary cognitions, sleepiness,
      quality of life, and perceived sexual health. Generalised linear mixed models
      will be used to assess all outcomes for the impact of group (Resources, Online,
      and Control), time (treated as categorical with levels baseline, 3-months and 6
      months) and the group-by-time interaction. These three terms will form the base
      model. 'Intention-to-treat' analysis will include all randomised participants.
      DISCUSSION: Our study will compare evidence-based and theoretically driven, low
      cost and easily disseminated strategies specifically targeting weight loss in
      men. The SHED-IT community trial will provide evidence to inform development and
      dissemination of sustainable strategies to reduce obesity in men. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      (ACTRN12610000699066).

PMID- 21078201
TI  - Response to Dengue virus infections altered by cytokine-like substances from
      mosquito cell cultures.
AB  - BACKGROUND: With both shrimp and commercial insects such as honey bees, it is
      known that stable, persistent viral infections characterized by absence of
      disease can sometimes shift to overt disease states as a result of various stress
      triggers and that this can result in serious economic losses. The main research
      interest of our group is to understand the dynamics of stable viral infections in
      shrimp and how they can be destabilized by stress. Since there are no continuous
      cell lines for crustaceans, we have used a C6/36 mosquito cell line infected with
      Dengue virus to test hypotheses regarding these interactions. As a result, we
      accidentally discovered two new cytokine-like substances in 5 kDa extracts from
      supernatant solutions of acutely and persistently infected mosquito cells.
      RESULTS: Naive C6/36 cells were exposed for 48 h to 5 kDa membrane filtrates
      prepared from the supernatant medium of stable C6/36 mosquito cell cultures
      persistently-infected with Dengue virus. Subsequent challenge of naive cells with
      a virulent stock of Dengue virus 2 (DEN-2) and analysis by confocal
      immunofluorescence microscopy using anti-DEN-2 antibody revealed a dramatic
      reduction in the percentage of DEN-2 infected cells when compared to control
      cells. Similar filtrates prepared from C6/36 cells with acute DEN-2 infections
      were used to treat stable C6/36 mosquito cell cultures persistently-infected with
      Dengue virus. Confocal immunofluorescence microscopy revealed destabilization in
      the form of an apoptosis-like response. Proteinase K treatment removed the cell
      altering activities indicating that they were caused by small polypeptides
      similar to those previously reported from insects. CONCLUSIONS: This is the first
      report of cytokine-like substances that can alter the responses of mosquito cells
      to Dengue virus. This simple model system allows detailed molecular studies on
      insect cytokine production and on cytokine activity in a standard insect cell
      line.

PMID- 21078202
TI  - Modulating effects of plasma containing anti-malarial antibodies on in vitro anti
      malarial drug susceptibility in Plasmodium falciparum.
AB  - BACKGROUND: The efficacy of anti-malarial drugs is determined by the level of
      parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics,
      and host factors including immunity. Host immunity improves the in vivo
      therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of
      this effect has not been characterized. This study characterized the effects of
      'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P.
      falciparum to anti-malarial drugs. METHODS: Titres of antibodies against blood
      stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were
      measured in plasma samples obtained from Thai patients with acute falciparum
      malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth
      and multiplication of the Thai P. falciparum laboratory strain TM267 were
      assessed by light microscopy. The in vitro susceptibility to quinine and
      artesunate was then determined in the presence and absence of 'immune' plasma
      using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was
      expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90),
      of 3H-hypoxanthine uptake. RESULTS: Incubation with 'immune' plasma reduced
      parasite maturation and decreased parasite multiplication in a dose dependent
      manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was
      decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269]
      cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma
      reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4
      (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had
      a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml
      versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low
      concentrations, changing the shape of the concentration-effect relationship. IC90
      values were not significantly affected; median (range) IC90 448.0 (65 to > 500)
      ng/ml versus 368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to
      29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4). CONCLUSIONS:
      'Immune' plasma containing anti-malarial antibodies inhibits parasite development
      and multiplication and increases apparent in vitro anti-malarial drug
      susceptibility of P. falciparum. The IC90 was much less affected than the IC50
      measurement.

PMID- 21078203
TI  - Evaluation of computerized health management information system for primary
      health care in rural India.
AB  - BACKGROUND: The Comprehensive Rural Health Services Project Ballabgarh, run by
      All India Institute of Medical Sciences (AIIMS), New Delhi has a computerized
      Health Management Information System (HMIS) since 1988. The HMIS at Ballabgarh
      has undergone evolution and is currently in its third version which uses generic
      and open source software. This study was conducted to evaluate the effectiveness
      of a computerized Health Management Information System in rural health system in
      India. METHODS: The data for evaluation were collected by in-depth interviews of
      the stakeholders i.e. program managers (authors) and health workers. Health
      Workers from AIIMS and Non-AIIMS Primary Health Centers were interviewed to
      compare the manual with computerized HMIS. A cost comparison between the two
      methods was carried out based on market costs. The resource utilization for both
      manual and computerized HMIS was identified based on workers' interviews.
      RESULTS: There have been no major hardware problems in use of computerized HMIS.
      More than 95% of data was found to be accurate. Health workers acknowledge the
      usefulness of HMIS in service delivery, data storage, generation of workplans and
      reports. For program managers, it provides a better tool for monitoring and
      supervision and data management. The initial cost incurred in computerization of
      two Primary Health Centers was estimated to be Indian National Rupee (INR)
      1674,217 (USD 35,622). Equivalent annual incremental cost of capital items was
      estimated as INR 198,017 (USD 4213). The annual savings is around INR 894,283
      (USD 11,924). CONCLUSION: The major advantage of computerization has been in
      saving of time of health workers in record keeping and report generation. The
      initial capital costs of computerization can be recovered within two years of
      implementation if the system is fully operational. Computerization has enabled
      implementation of a good system for service delivery, monitoring and supervision.

PMID- 21078204
TI  - Tumour auto-antibody screening: performance of protein microarrays using SEREX
      derived antigens.
AB  - BACKGROUND: The simplicity and potential of minimal invasive testing using serum
      from patients make auto-antibody based biomarkers a very promising tool for use
      in diagnostics of cancer and auto-immune disease. Although several methods exist
      for elucidating candidate-protein markers, immobilizing these onto membranes and
      generating so called macroarrays is of limited use for marker validation.
      Especially when several hundred samples have to be analysed, microarrays could
      serve as a good alternative since processing macro membranes is cumbersome and
      reproducibility of results is moderate. METHODS: Candidate markers identified by
      SEREX (serological identification of antigens by recombinant expression cloning)
      screenings of brain and lung tumour were used for macroarray and microarray
      production. For microarray production recombinant proteins were expressed in E.
      coli by autoinduction and purified His-tag (histidine-tagged) proteins were then
      used for the production of protein microarrays. Protein arrays were hybridized
      with the serum samples from brain and lung tumour patients. RESULT: Methods for
      the generation of microarrays were successfully established when using antigens
      derived from membrane-based selection. Signal patterns obtained by microarrays
      analysis of brain and lung tumour patients' sera were highly reproducible (R =
      0.92-0.96). This provides the technical foundation for diagnostic applications on
      the basis of auto-antibody patterns. In this limited test set, the assay provided
      high reproducibility and a broad dynamic range to classify all brain and lung
      samples correctly. CONCLUSION: Protein microarray is an efficient means for auto
      antibody-based detection when using SEREX-derived clones expressing antigenic
      proteins. Protein microarrays are preferred to macroarrays due to the easier
      handling and the high reproducibility of auto-antibody testing. Especially when
      using only a few microliters of patient samples protein microarrays are ideally
      suited for validation of auto-antibody signatures for diagnostic purposes.

PMID- 21078205
TI  - Significant association between polymorphism of the erythropoietin gene promoter
      and myelodysplastic syndrome.
AB  - BACKGROUND: Myelodysplastic syndrome (MDS) may be induced by certain mutagenic
      environmental or chemotherapeutic toxins; however, the role of susceptibility
      genes remains unclear. The G/G genotype of the single-nucleotide polymorphism
      (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be
      associated with decreased EPO expression. We examined the association of
      rs1617640 genotype with MDS. METHODS: We genotyped the EPO rS1617640 SNP in 189
      patients with MDS, 257 with acute myeloid leukemia (AML), 106 with acute
      lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic
      myeloid leukemia, and 95 healthy controls. RESULTS: The G/G genotype was
      significantly more common in MDS patients (47/187; 25.1%) than in controls (6/95;
      6.3%) or in patients with other leukemias (101/813; 12.4%) (all P < 0.001).
      Individuals with the G/G genotype were more likely than those with other
      genotypes to have MDS (odd ratio = 4.98; 95% CI = 2.04-12.13). Clinical and
      follow up data were available for 112 MDS patients and 186 AML patients. There
      was no correlation between EPO promoter genotype and response to therapy or
      overall survival in MDS or AML. In the MDS group, the GG genotype was
      significantly associated with shorter complete remission duration, as compared
      with the TT genotype (P = 0.03). Time to neutrophils recovery after therapy was
      significantly longer in MDS patients with the G/G genotype (P = 0.02).
      CONCLUSIONS: These findings suggest a strong association between the rs1617640
      G/G genotype and MDS. Further studies are warranted to investigate the utility of
      screening for this marker in individuals exposed to environmental toxins or
      chemotherapy.

PMID- 21078206
TI  - A tryptophan-rich peptide acts as a transcription activation domain.
AB  - BACKGROUND: Eukaryotic transcription activators normally consist of a sequence
      specific DNA-binding domain (DBD) and a transcription activation domain (AD).
      While many sequence patterns and motifs have been defined for DBDs, ADs do not
      share easily recognizable motifs or structures. RESULTS: We report herein that
      the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when
      fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct
      LexA-responsive promoters. The transcriptional activity was mainly attributed to
      a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably,
      the pentapeptide per se retained much of the transcriptional activity. Mutations
      which substituted tryptophan residues for both of the non-tryptophan residues in
      the pentapeptide (resulting in W5) significantly enhanced its activity (~1.8
      fold), while mutations which substituted aromatic residues with alanine residues
      severely impaired its activity. Accordingly, a much more active peptide,
      pentatryptophan (W7), was produced, which elicited ~3-fold higher activity than
      that of the native pentapeptide and the N domain. Further study indicated that W7
      mediates transcription activation through interacting with the general
      transcription factor, TFIIB. CONCLUSIONS: Since W7 shares no sequence homology or
      features with any known transcription activators, it may represent a novel class
      of AD.

PMID- 21078207
TI  - Serosurvey for selected pathogens in Iberian roe deer.
AB  - BACKGROUND: The roe deer is the most abundant and widespread wild Eurasian
      cervid. Its populations are expanding and increasingly in contact with livestock.
      This may affect the distribution of infectious diseases shared with other wild
      and domestic ungulates. METHODS: We investigated the antibody seroprevalence
      against Pestivirus, Herpesvirus, Bluetongue (BT) virus, M. avium paratuberculosis
      (MAP), and Brucella sp. in 519 roe deer from different regions in Spain, south
      western Europe. RESULTS: No antibodies were detected against BT and Brucella sp.
      However, antibodies were detected against Pestivirus (1.5%), Herpesvirus (0.2%)
      and MAP (9.2%). MAP antibodies were detected in seven of the eight populations
      (range 5-16.4%). CONCLUSIONS: The detection of MAP antibodies in samples from
      most roe deer populations suggests that contact with MAP is widespread in this
      wildlife species. The highest prevalence was detected in sites with abundant
      dairy cattle and frequent use of liquid manure on pastures. Considering the
      results obtained regarding exposure to different pathogens, we suggest that
      antibody prevalences in this non-gregarious browser are largely determined by
      environmental factors, potentially modulating vector populations or pathogen
      survival in the environment.

PMID- 21078208
TI  - An investigation on the presence of Chlamydiaceae in Swedish dogs.
AB  - BACKGROUND: Bacteria belonging to the family Chlamydiaceae cause a broad spectrum
      of diseases in a wide range of hosts, including man, other mammals, and birds.
      Upper respiratory and genital diseases are common clinical problems caused by
      Chlamydiaceae. Very little is known about chlamydial infections in dogs. Few
      clinical reports on natural disease in dogs describe mainly conjunctival and
      upper respiratory signs, and the role of Chlamydiaceae in genital disease is
      unclear. The present study aimed at studying the prevalence of Chlamydiaceae in
      healthy dogs and in dogs with genital or upper respiratory disease, including
      conjunctivitis. METHODS: A real-time polymerase chain reaction (PCR) for
      Chlamydiaceae was used to detect any chlamydial species within this family. Swab
      samples from the conjunctiva and the mucosal membranes of the oropharynx, rectum
      and genital tract were taken from 79 dogs: 27 clinically healthy dogs, 25 dogs
      with clinical signs from the genital tract and 28 dogs with conjunctivitis. There
      were 52 female and 27 male dogs. From 7 of the male dogs, additional semen
      samples were analysed. RESULTS: No Chlamydiaceae were detected from any dog.
      CONCLUSIONS: Although the number of dogs that was included is limited, the
      results suggest that cases of Chlamydiaceae in dogs probably are related to
      infection from other species, and that dogs in general do not harbour
      Chlamydiaceae. Bacteria belonging to the family Chlamydiaceae do not seem to be
      of major importance for genital or ocular disease in Swedish dogs.

PMID- 21078210
TI  - Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection.
      Glasgow, United Kingdom. November 7-11, 2010.

PMID- 21078209
TI  - Cotton domestication: dramatic changes in a single cell.
AB  - Investigations on the nature of genetic changes underpinning plant domestication
      have begun to shed light on the evolutionary history of crops and can guide
      improvements to modern cultivars. A recent study focused on cotton fiber cells
      tracks the dramatic genome-wide changes in gene expression during development
      that have accompanied selection for increased fiber yield and quality.

PMID- 21078211
TI  - The efficacy of n-3 fatty acids DHA and EPA (fish oil) for perinatal depression.
AB  - Depressive symptoms are common during pregnancy and the post-partum period.
      Although essential n-3 PUFA may have beneficial effects on depression, it remains
      unclear whether they are also effective for perinatal depression. The purpose of
      the present study was to assess the efficacy of n-3 supplementation for perinatal
      depression, by performing a meta-analysis on currently available data. After a
      thorough literature search, we included seven randomised controlled trials in the
      meta-analysis, all with EPA and/or DHA supplementation. Most studies were judged
      to be of low-to-moderate quality, mainly due to small sample sizes and failure to
      adhere to Consolidated Standards of Reporting Trials guidelines. Some studies
      were not primarily designed to address perinatal depression. A total of 309 women
      on n-3 fatty acid supplementation were compared with 303 women on placebo
      treatment. n-3 Supplementation was not found to be significantly more effective
      than placebo at post-treatment with a pooled effect size (Hedges's g) of - 0.03
      (95 % CI - 0.18, 0.13; P = 0.76) using a fixed-effects model. Heterogeneity was
      low-to-moderate (I2 = 30 %). In a subgroup analysis of three small studies of
      pregnant women with major depression, there was some indication of effectiveness
      (effect size 0.17; 95 % CI - 0.21, 0.55). In conclusion, the question of whether
      EPA and DHA administration is effective in the prevention or treatment of
      perinatal depression cannot be answered yet. Future research should focus on
      women who are clinically depressed (or at risk). The quality of research in this
      area needs to improve.

PMID- 21078212
TI  - The antioxidant role of Sideritis caesarea infusion against TCA toxicity in rats.
AB  - Sideritis caesarea (SC) Duman, Aytac & Baser is a member of the Lamiaceae family.
      The present study was designed to investigate the antioxidant properties of the
      aerial parts of island green tea SC against TCA effects in rats. Biomarkers
      selected for monitoring antioxidant capacity were the activities of glutathione
      reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase, catalase
      (CAT), GSH level and malondialdehyde (MDA) content in various organs of rats.
      Three experimental groups, A (untreated = control), B (only TCA-treated) and C
      (TCA+SC-treated), were studied. At the end of the 50 d experiment, the MDA
      content in tissues increased significantly in group B, whereas no significant
      changes were observed in group C as compared with that of the control group.
      Antioxidant enzyme activities such as SOD and CAT increased significantly in the
      brain, liver and kidneys of group B but decreased significantly in group C as
      compared with group B. The GSH level and GR activity increased significantly in
      the brain and liver of group C as compared with the control and TCA-exposed rats.
      Hence, the study reveals that the constituents present in SC impart protection
      against chemical-induced oxidative injury that may result in the development of
      cancer.

PMID- 21078213
TI  - Curcumin induces paraoxonase 1 in cultured hepatocytes in vitro but not in mouse
      liver in vivo.
AB  - Paraoxonase 1 (PON1) is an enzyme that is mainly synthesised in the liver and
      protects LDL from oxidation, thereby exhibiting antiatherogenic properties. Using
      a luciferase reporter gene assay, we tested curcumin for its ability to induce
      PON1 in Huh7 hepatocytes in culture. Curcumin ( >= 10 MUmol/l) dose-dependently
      induced PON1 transactivation in Huh7 cells. However, dietary supplementation of
      female B6C3F1 mice with curcumin (500 mg/kg diet) for 2 weeks did not increase
      the hepatic PON1 mRNA and protein levels. No curcumin was detectable in the
      plasma of the 12 h fasted mice. In conclusion, curcumin may be a potent PON1
      inducer in cultured cells in vitro, but not in the liver of curcumin-fed mice
      because of its low concentrations in vivo.

PMID- 21078214
TI  - Do television food advertisements portray advertised foods in a 'healthy' food
      context?
AB  - Exposure to food promotion influences food preferences and diet. As food
      advertisements tend to promote 'less healthy' products, food advertising probably
      plays some role in the 'obesity epidemic'. Amid calls for increased regulation,
      food manufacturers are beginning to engage in a variety of health-promoting
      marketing initiatives. Positioning products in the context of a 'healthy',
      balanced diet in television advertisements is one such initiative. We explored
      whether the wider food context in which foods are advertised on television are
      'healthier' than the advertised foods themselves. All foods shown in food
      advertisements broadcast during 1 week on one commercial UK channel were
      identified and classified as 'primary' (i.e. the focus of advertisements) or
      'incidental'. The nutritional content of all foods was determined and that of
      primary and incidental foods were compared. Almost two-thirds of food
      advertisements did not include any incidental foods. When a wider food context
      was present, this tended to be 'healthier' than the primary foods that were the
      focus of food advertisements - particularly in terms of the food groups
      represented. It is not yet clear what effect this may have on consumers'
      perceptions and behaviour, and whether or not this practice should be encouraged
      or discouraged from a public health perspective.

PMID- 21078215
TI  - Ten-year myringoplasty series: does the cause of perforation affect the success
      rate?
AB  - OBJECTIVE: To present the results of primary myringoplasty procedures together
      with the perforation cause, perforation size and site, surgeon's experience, and
      surgical method, and to investigate how these factors relate to graft 'take'
      rates. STUDY DESIGN: Retrospective chart review of 243 consecutive patients
      undergoing primary myringoplasty with temporalis fascia underlay over a 10-year
      period from 1994 to 2004. RESULTS: The overall graft take rate was 95 per cent.
      The retroauricular approach resulted in a 97 per cent graft take rate, whereas a
      significantly lower rate (77 per cent) was seen for surgery conducted via the
      endaural approach, or via an ear speculum. There was no relationship between
      other factors and tympanic membrane healing. CONCLUSION: No association was found
      between perforation cause and graft take rate. The underlay technique is safe and
      reliable, and the retroauricular approach is preferable as it enables good
      surgical access and has better results.

PMID- 21078216
TI  - Protective effects of brain-derived neurotrophic factor on the noise-damaged
      cochlear spiral ganglion.
AB  - OBJECTIVE: To explore the protective effects of brain-derived neurotrophic factor
      on the noise-damaged cochlear spiral ganglion. METHODS: Recombinant adenovirus
      brain-derived neurotrophic factor vector, recombinant adenovirus LacZ and
      artificial perilymph were prepared. Guinea pigs with audiometric auditory
      brainstem response thresholds of more than 75 dB SPL, measured seven days after
      four hours of noise exposure at 135 dB SPL, were divided into three groups.
      Adenovirus brain-derived neurotrophic factor vector, adenovirus LacZ and
      perilymph were infused into the cochleae of the three groups, variously. Eight
      weeks later, the cochleae were stained immunohistochemically and the spiral
      ganglion cells counted. RESULTS: The auditory brainstem response threshold
      recorded before and seven days after noise exposure did not differ significantly
      between the three groups. However, eight weeks after cochlear perfusion, the
      group receiving brain-derived neurotrophic factor had a significantly decreased
      auditory brainstem response threshold and increased spiral ganglion cell count,
      compared with the adenovirus LacZ and perilymph groups. CONCLUSION: When
      administered via cochlear infusion following noise damage, brain-derived
      neurotrophic factor appears to improve the auditory threshold, and to have a
      protective effect on the spiral ganglion cells.

PMID- 21078217
TI  - Development of an auditory implant manipulator for minimally invasive surgical
      insertion of implantable hearing devices.
AB  - OBJECTIVE: To present the auditory implant manipulator, a navigation-controlled
      mechanical and electronic system which enables minimally invasive ('keyhole')
      transmastoid access to the tympanic cavity. MATERIALS AND METHODS: The auditory
      implant manipulator is a miniaturised robotic system with five axes of movement
      and an integrated drill. It can be mounted on the operating table. We evaluated
      the surgical work field provided by the system, and the work sequence involved,
      using an anatomical whole head specimen. RESULTS: The work field provided by the
      auditory implant manipulator is considerably greater than required for
      conventional mastoidectomy. The work sequence for a keyhole procedure included
      pre-operative planning, arrangement of equipment, the procedure itself and post
      operative analysis. CONCLUSION: Although system improvements are necessary, our
      preliminary results indicate that the auditory implant manipulator has the
      potential to perform keyhole insertion of implantable hearing devices.

PMID- 21078218
TI  - Bronchoscopy versus multi-detector computed tomography in the diagnosis of
      congenital vascular ring.
AB  - BACKGROUND: Vascular rings are congenital vascular anomalies of the aortic arch
      complex which cause compression of the trachea and/or oesophagus. A variety of
      investigations may lead to diagnosis of these anomalies, including bronchoscopy
      and computed tomography. During the latter, image acquisition and processing use
      the multi-detector row technique and new reconstruction algorithms, producing
      high-resolution images which can be visualised as complex, three-dimensional
      renditions. OBJECTIVE: This study aimed to assess and compare the roles of
      bronchoscopy and multi-detector row computed tomography in the diagnosis of
      congenital vascular ring. PATIENTS AND METHODS: We included infants and children
      below the age of 16 years who presented with congenital vascular ring. All
      patients underwent rigid bronchoscopy under general anaesthesia, with spontaneous
      respiration. All computed tomography scans were obtained using a 16 multi
      detector row computed tomography system, followed by data reconstruction on a
      three-dimensional workstation. RESULTS: Ten patients with congenital vascular
      ring were identified (six boys and four girls). Fifty per cent of cases presented
      within the first year of life. Double aortic arch was the most common anomaly (40
      per cent). Bronchoscopy detected external tracheal compression in nine cases (90
      per cent). Associated airway lesions were detected endoscopically in three cases.
      In contrast, multi-detector row computed tomography detected the vascular ring in
      all cases, with accurate detection of the compressing vessel; however, it did not
      detect any associated airway lesions. CONCLUSION: Bronchoscopy and radiological
      evaluation are essential for the diagnosis and pre-operative evaluation of
      congenital vascular ring. Multi-detector row computed tomography can provide more
      information about the nature of the disease, and can facilitate better
      communication between clinicians, compared with conventional computed tomography.

PMID- 21078219
TI  - Parapharyngeal cerebrospinal fluid collection: an unusual complication of
      temporal bone fracture.
AB  - OBJECTIVE: We present an unusual case of parapharyngeal cerebrospinal fluid
      collection causing upper airway obstruction following a temporal bone fracture.
      METHOD: Case report and literature review of temporal bone fracture associated
      with parapharyngeal cerebrospinal fluid collection. RESULTS: A 19-year-old man
      presented with cerebrospinal fluid otorrhoea and temporal bone fracture following
      a head injury. He was discharged after 48 hours of observation. The patient
      returned within 6 hours with sudden unilateral neck swelling and stridor after
      blowing his nose. Flexible nasendoscopy and computed tomography showed extrinsic
      compression of the pharynx, with partial upper airway obstruction. A literature
      review using PubmedTM and MedlineTM identified no previously reported cases of
      parapharyngeal cerebrospinal fluid collection associated with temporal bone
      fracture. CONCLUSION: This case illustrates a previously undescribed complication
      of temporal bone fracture. Raised intracranial pressure in the presence of a
      cerebrospinal fluid fistula may lead to airway obstruction, following temporal
      bone fracture.

PMID- 21078220
TI  - A global sensitivity analysis for African sleeping sickness.
AB  - African sleeping sickness is a parasitic disease transmitted through the bites of
      tsetse flies of the genus Glossina. We constructed mechanistic models for the
      basic reproduction number, R0, of Trypanosoma brucei gambiense and Trypanosoma
      brucei rhodesiense, respectively the causative agents of West and East African
      human sleeping sickness. We present global sensitivity analyses of these models
      that rank the importance of the biological parameters that may explain variation
      in R0, using parameter ranges based on literature, field data and expertize out
      of Uganda. For West African sleeping sickness, our results indicate that the
      proportion of bloodmeals taken from humans by Glossina fuscipes fuscipes is the
      most important factor, suggesting that differences in the exposure of humans to
      tsetse are fundamental to the distribution of T. b. gambiense. The second ranked
      parameter for T. b. gambiense and the highest ranked for T. b. rhodesiense was
      the proportion of Glossina refractory to infection. This finding underlines the
      possible implications of recent work showing that nutritionally stressed tsetse
      are more susceptible to trypanosome infection, and provides broad support for
      control strategies in development that are aimed at increasing refractoriness in
      tsetse flies. We note though that for T. b. rhodesiense the population parameters
      for tsetse - species composition, survival and abundance - were ranked almost as
      highly as the proportion refractory, and that the model assumed regular treatment
      of livestock with trypanocides as an established practice in the areas of Uganda
      experiencing East African sleeping sickness.

PMID- 21078221
TI  - Seasonal variation in the effect of climate on the biology of Rhipicephalus
      sanguineus in southern Europe.
AB  - OBJECTIVE: Rhipicephalus sanguineus is the most widespread tick in the world and
      a vector of many pathogens infecting dogs and humans. To date, there have been no
      investigations on the biology of R. sanguineus under natural Mediterranean
      climatic conditions. METHODS: The biology of R. sanguineus was studied under
      laboratory and natural climatic conditions in southern Italy. Several biological
      parameters were compared in different seasons, and their correlation with
      climatic data was assessed. RESULTS: The life cycle of R. sanguineus lasted for a
      mean of 101.4 and 116.2 days under laboratory and environmental conditions
      respectively. Reproductive parameters of wild-collected females kept in the
      environment in May were significantly different from first-generation females
      maintained in September-October, and the correlation between reproductive
      parameters and climate data varied according to season. CONCLUSION: These results
      indicate that the Mediterranean climate affects the biology of R. sanguineus,
      which compensates its losses during the initial phases of its cycle in spring
      with high feeding and moulting rates of larvae and nymphs during summer as well
      as with high egg production during autumn. These results advance our knowledge of
      the biology of R. sanguineus and will be useful for the understanding of the eco
      epidemiology of tick-borne diseases that this tick transmits.

PMID- 21078222
TI  - Molecular approaches for a better understanding of the epidemiology and
      population genetics of Leishmania.
AB  - Molecular approaches are being used increasingly for epidemiological studies of
      visceral and cutaneous leishmaniases. Several molecular markers resolving genetic
      differences between Leishmania parasites at species and strain levels have been
      developed to address key epidemiological and population genetic questions. The
      current gold standard, multilocus enzyme typing (MLEE), needs cultured parasites
      and lacks discriminatory power. PCR assays identifying species directly with
      clinical samples have proven useful in numerous field studies. Multilocus
      sequence typing (MLST) is potentially the most powerful phylogenetic approach and
      will, most probably, replace MLEE in the future. Multilocus microsatellite typing
      (MLMT) is able to discriminate below the zymodeme level and seems to be the best
      candidate for becoming the gold standard for distinction of strains. Population
      genetic studies by MLMT revealed geographical and hierarchic population structure
      in L. tropica, L. major and the L. donovani complex. The existence of hybrids and
      gene flow between Leishmania populations suggests that sexual recombination is
      more frequent than previously thought. However, typing and analytical tools need
      to be further improved. Accessible databases should be created and sustained for
      integrating data obtained by different researchers. This would allow for global
      analyses and help to avoid biases in analyses due to small sample sizes.

PMID- 21078223
TI  - Efficacy of two praziquantel treatments among primary school children in an area
      of high Schistosoma mansoni endemicity, Nile Delta, Egypt.
AB  - Praziquantel is the cornerstone of schistosomiasis control. A number of reports
      from endemic areas suggest that resistance or tolerance to praziquantel might
      exist in Schistosoma mansoni. Several explanations were postulated. The present
      work was designed to test the hypothesis that a low praziquantel (pzq) cure rate
      in Egypt is due to survival and maturation of immature stages that escaped pzq,
      which is effective against mature S. mansoni worms only. The study sample
      included 1351 children attending El Rouse primary school located in El Rouse
      village, Nile Delta, Egypt. All children received 2 pzq doses (40 mg/kg) 4 weeks
      apart. Diagnosis of S. mansoni infection and cure assessment were based on
      examination of 2 Kato slides prepared from a single stool sample collected before
      and 4 weeks after the first and second treatments. The cure rate was 78.8% after
      the first treatment and increased significantly to 90.8% after the second
      treatment. Egg reduction rates were 71.2% and 77.2% after 1 and 2 treatments
      respectively. Pre-treatment intensity of infection has a great influence on cure
      and egg reduction rates. Our results confirmed that low praziquantel cure rate,
      in Egypt, might be attributed, even partially, to survival and maturation of the
      immature S. mansoni stages that escaped pzq that is effective against mature
      worms only.

PMID- 21078225
TI  - The generalizability of antidepressant efficacy trials to routine psychiatric out
      patient practice.
AB  - BACKGROUND: Generalizability of antidepressant efficacy trials (AETs) to daily
      practice is questioned because of their very stringent patient selection. This
      study aims to determine eligibility for AETs of out-patients suffering from major
      depression in a routine out-patient setting and investigates influence of
      eligibility on treatment outcome. METHOD: Data collection (n = 1653) was
      performed through routine outcome monitoring by independent trained research
      nurses. The Mini-International Neuropsychiatric Interview Plus and the
      Dimensional Assessment of Personality Pathology, short Dutch version were used
      for diagnostic assessment and personality pathology screening. The Montgomery
      Asberg Depression Rating Scale (MADRS) was used for assessment of baseline
      severity and treatment outcome. Eligibility was assessed by stepwise application
      of commonly used exclusion criteria. Influence of eligibility on treatment
      outcome was investigated in a subsample of the 1653 patients who had at least one
      follow-up assessment (n = 626). Eligible and non-eligible patients were compared
      on proportion of response (50% reduction) and remission on MADRS (MADRS <= 10).
      RESULTS: Altogether, 17-25% of the patients were eligible for AETs. The most
      common reasons for exclusion would be 'not meeting minimum baseline severity' and
      'presence of co-morbid Axis I disorder'. Eligible and non-eligible patients did
      not differ in treatment outcome. Only 'meeting the minimum baseline severity' is
      associated with remission. CONCLUSIONS: The majority of 'real life' out-patients
      are not eligible for AETs. However, the influence of eligibility on treatment
      outcome seems to be small. This suggests that stringent patient selection by
      eligibility criteria is not the major reason for lack of generalizability of
      AETs. Exclusion of less severely depressed patients from the analyses resulted in
      better treatment outcome. Milder depression is highly prevalent in daily practice
      and more research into treatment effectiveness in milder depression is warranted.

PMID- 21078224
TI  - Visual masking by object substitution in schizophrenia.
AB  - BACKGROUND: Schizophrenia patients demonstrate impairment on visual backward
      masking, a measure of early visual processing. Most visual masking paradigms
      involve two distinct processes, an early fast-acting component associated with
      object formation and a later component that acts through object substitution. So
      far, masking paradigms used in schizophrenia research have been unable to
      separate these two processes. METHOD: We administered three visual processing
      paradigms (location masking with forward and backward masking, four-dot backward
      masking and a cuing task) to 136 patients with schizophrenia or schizoaffective
      disorder and 79 healthy controls. A psychophysical procedure was used to match
      subjects on identification of an unmasked target prior to location masking.
      Location masking interrupts object formation, four-dot masking task works through
      masking by object substitution and the cuing task measures iconic decay. RESULTS:
      Patients showed impairment on location masking after being matched for input
      threshold, similar to previous reports. After correcting for age, patients showed
      lower performance on four-dot masking than controls, but the groups did not
      differ on the cuing task. CONCLUSIONS: Patients with schizophrenia showed lower
      performance when masking was specific to object substitution. The difference in
      object substitution masking was not due to a difference in rate of iconic decay,
      which was comparable in the two groups. These results suggest that, despite
      normal iconic decay rates, individuals with schizophrenia show impairment in a
      paradigm of masking by object substitution that did not also involve disruption
      of object formation.

PMID- 21078226
TI  - Pre-adult versus adult onset major depressive disorder in a naturalistic patient
      sample: the Leiden Routine Outcome Monitoring Study.
AB  - BACKGROUND: Pre-adult onset of major depressive disorder (MDD) may predict a more
      severe phenotype of depression. As data from naturalistic psychiatric specialty
      care settings are scarce, we examined phenotypic differences between pre-adult
      and adult onset MDD in a large sample of consecutive out-patients. METHOD:
      Altogether, 1552 out-patients, mean age 39.2 +/- 11.6 years, were diagnosed with
      current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic
      interview as part of the usual diagnostic procedure. A total of 1105 patients
      (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD
      was defined as having experienced the signs and symptoms of a first major
      depressive episode before the age of 18 years. Patients were stratified according
      to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were
      analysed using logistic regression models adjusted for age, age squared and
      gender. RESULTS: Univariate analyses showed that pre-adult onset of MDD had a
      distinct set of demographic (e.g. less frequently living alone) and clinical
      correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia,
      more suicidality). In the multivariate model, we found an independent association
      only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence
      intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26
      2.60) in patients with pre-adult versus adult onset MDD. CONCLUSIONS: Pre-adult
      onset of MDD is associated with more suicidality than adult onset MDD. Age of
      onset of depression is an easy to ascertain characteristic that may help
      clinicians in weighing suicide risk.

PMID- 21078227
TI  - Voxel-based meta-analysis of regional white-matter volume differences in autism
      spectrum disorder versus healthy controls.
AB  - BACKGROUND: We conducted a meta-analysis of voxel-based morphometry (VBM) studies
      in autism spectrum disorder (ASD) to clarify the changes in regional white-matter
      volume underpinning this condition, and generated an online database to
      facilitate replication and further analyses by other researchers. METHOD: PubMed,
      ScienceDirect, Web of Knowledge and Scopus databases were searched between 2002
      (the date of the first white-matter VBM study in ASD) and 2010. Manual searches
      were also conducted. Authors were contacted to obtain additional data.
      Coordinates were extracted from clusters of significant white-matter difference
      between patients and controls. A new template for white matter was created for
      the signed differential mapping (SDM) meta-analytic method. A diffusion tensor
      imaging (DTI)-derived atlas was used to optimally localize the changes in white
      matter volume. RESULTS: Thirteen datasets comprising 246 patients with ASD and
      237 healthy controls met inclusion criteria. No between-group differences were
      found in global white-matter volumes. ASD patients showed increases of white
      matter volume in the right arcuate fasciculus and also in the left inferior
      fronto-occipital and uncinate fasciculi. These findings remained unchanged in
      quartile and jackknife sensitivity analyses and also in subgroup analyses
      (pediatric versus adult samples). CONCLUSIONS: Patients with ASD display
      increases of white-matter volume in tracts known to be important for language and
      social cognition. Whether the results apply to individuals with lower IQ or
      younger age and whether there are meaningful neurobiological differences between
      the subtypes of ASD remain to be investigated.

PMID- 21078228
TI  - Effects of a CACNA1C genotype on attention networks in healthy individuals.
AB  - BACKGROUND: Recent genetic studies found the A allele of the variant rs1006737 in
      the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene
      to be over-represented in patients with psychosis, including schizophrenia,
      bipolar disorder and major depressive disorder. In these disorders, attention
      deficits are among the main cognitive symptoms and have been related to altered
      neural activity in cerebral attention networks. The particular effect of CACNA1C
      on neural function, such as attention networks, remains to be elucidated. METHOD:
      The current event-related functional magnetic resonance imaging (fMRI) study
      investigated the effect of the CACNA1C gene on brain activity in 80 subjects
      while performing a scanner-adapted version of the Attention Network Test (ANT).
      Three domains of attention were probed simultaneously: alerting, orienting and
      executive control of attention. RESULTS: Risk allele carriers showed impaired
      performance in alerting and orienting in addition to reduced neural activity in
      the right inferior parietal lobule [Brodmann area (BA) 40] during orienting and
      in the medial frontal gyrus (BA 8) during executive control of attention. These
      areas belong to networks that have been related to impaired orienting and
      executive control mechanisms in neuropsychiatric disorders. CONCLUSIONS: Our
      results suggest that CACNA1C plays a role in the development of specific
      attention deficits in psychiatric disorders by modulation of neural attention
      networks.

PMID- 21078229
TI  - The Hayes principles: learning from the national pilot of information technology
      and core generalisable theory in informatics.
AB  - BACKGROUND: There has been much criticism of the NHS national programme for
      information technology (IT); it has been an expensive programme and some elements
      appear to have achieved little. The Hayes report was written as an independent
      review of health and social care IT in England. OBJECTIVE: To identify key
      principles for health IT implementation which may have relevance beyond the
      critique of NHS IT. OUTCOME: We elicit ten principles from the Hayes report,
      which if followed may result in more effective IT implementation in health care.
      They divide into patient-centred, subsidiarity and strategic principles. The
      patient-centred principles are: 1) the patient must be at the centre of all
      information systems; 2) the provision of patient-level operational data should
      form the foundation - avoid the dataset mentality; 3) store health data as close
      to the patient as possible; 4) enable the patient to take a more active role with
      their health data within a trusted doctor-patient relationship. The subsidiarity
      principles set out to balance the local and health-system-wide needs: 5)
      standardise centrally - patients must be able to benefit from interoperability;
      6) provide a standard procurement package and an approved process that ensures
      safety standards and provision of interoperable systems; 7) authorise a range of
      local suppliers so that health providers can select the system best meeting local
      needs; 8) allow local migration from legacy systems, as and when improved
      functionality for patients is available. And finally the strategic principles: 9)
      evaluate health IT systems in terms of measureable benefits to patients; 10)
      strategic planning of systems should reflect strategic goals for the health of
      patients/the population. CONCLUSIONS: Had the Hayes principles been embedded
      within our approach to health IT, and in particular to medical record
      implementation, we might have avoided many of the costly mistakes with the UK
      national programme. However, these principles need application within the modern
      IT environment. Closeness to the patient must not be interpreted as physical but
      instead as a virtual patient-centred space; data will be secure within the cloud
      and we should dump the vault and infrastructure mentality. Health IT should be
      developed as an adaptive ecosystem.

PMID- 21078230
TI  - The NHS information technology (IT) and social care review 2009: a synopsis.
AB  - BACKGROUND: England's National Health Service information technology (NHS IT) has
      been much criticised in a number of major governmental and non-governmental
      reports. The author was requested to write a review of NHS IT to help formulate
      policy. OBJECTIVE: To identify what had worked and should be continued and what
      was unhelpful and should be dropped from NHS IT. METHOD: Iterative process of
      debate with a committee of experts. RESULTS: The theme areas which emerged were:
      * the central importance of the record to serving individual patient care, and
      that this should be top priority * development of systems should be carried out
      as close as possible to the front-line clinicians who use them * standards and
      frameworks are useful centralised functions; whereas imposing detailed technical
      solutions across large geographical areas is unlikely to succeed and should be
      abandoned. CONCLUSIONS: IT should be seen as a clinical tool in health care,
      developed to meet the needs of patients and front-line clinicians.

PMID- 21078231
TI  - Evaluation of a new short generic measure of health status: howRu.
AB  - BACKGROUND: Quality of life is paramount for patients and clinicians, but
      existing measures of health were not developed for routine use. OBJECTIVES: This
      paper describes the development and testing of a new generic tool for measuring
      health related quality of life (HRQoL) with direct comparison to the SF-12 Health
      Survey. METHODS: The new tool (howRu) has four items (discomfort, distress,
      disability and dependence), rated using four levels (none, a little, quite a lot
      and extreme), providing 256 possible states (4(4)); it has an aggregate scoring
      scheme with a range from 0 (worst) to 12 (best). Psychometric properties were
      examined in a telephone survey, which also recorded SF-12. RESULTS: The howRu
      script is shorter than SF-12 (45 words vs 294 words) and has better readability
      statistics. 2751 subjects, all with long-term conditions (average age 62, female
      62.8%), completed the survey; 21.7% were at the ceiling (no reported problems on
      any dimension); 0.9% at the floor. Inter-item correlations, Cronbach's alpha and
      principal factor analysis suggest that a single summary score is appropriate.
      Correlations between the physical and mental components of both howRu and SF-12
      were as expected. Across all patients the howRu score was correlated with PCS-12
      (r=0.74), MCS-12 (r=0.49) and the sum of PCS-12 and MCS-12 (r=0.81). Subjects
      were classified by howRu score, primary condition, the number of conditions
      suffered, age group, duration of illness and area of residence. Across all six
      classifications, the correlation of the mean howRu score with the mean PCS-12 for
      each class was r=0.91, with MCS-12, r=0.45 and with the sum of PCS-12 and MCS-12,
      r=0.97. CONCLUSIONS: howRu is a new short generic measure of HRQoL, with good
      psychometric properties. It generates similar aggregate results to SF-12. It
      could provide a quick and easy way for practitioners to monitor the health of
      patients with long-term conditions.

PMID- 21078232
TI  - Radiological exposure evaluation through the computerised electronic records
      system as decisional support to X-ray examination justification in family
      medicine.
AB  - BACKGROUND: In recent decades, patients' exposure to ionising radiation (IR)
      during diagnostic examinations has increased a great deal. X-ray requests do not
      always conform to the principle of 'justification', which emphasises the real
      utility and necessity of the examination. Databases maintained by general
      practitioners usually record all requests for radiological examinations of their
      patients and could be configured to assess the radiological risk for each
      patient. OBJECTIVE: To show, through the analysis of the data extracted from a
      database commonly used by Italian general practitioners, whether it is possible
      to measure patients' exposure to IR in the previous five years, so that doctors
      are aware of this when they refer patients for examination involving further
      exposure to radiation. METHOD: Records of 120 patients from an Italian general
      practice were randomly extracted from the practice database. The patients were a
      mix of male and female, aged from 15 to 64 years. All radiological examinations
      performed in the previous five years were recorded in a special spreadsheet,
      which had been created for computing the exposure to ionising radiation in
      milliSiviert. RESULTS: The calculated cumulative exposure of the 120 patients
      showed a very different perspective, which could help doctors when applying the
      principle of justification and allow accurate information to be communicated to
      the patient concerning their relevant health problem. CONCLUSIONS: Databases
      maintained by general practitioners could easily be configured to automatically
      compute the radiological risk for each patient and to alert the doctor when an X
      ray examination is prescribed, giving the doctor crucial decisional support for
      its justification.

PMID- 21078233
TI  - Quality assessment of information about medications in primary care electronic
      patient record (EPR) systems.
AB  - BACKGROUND: Many different brands of primary care electronic patient record (EPR)
      software are available to general practitioners (GPs). Their ability to support
      GPs in improving prescribing varies greatly. OBJECTIVE: To assess, using a ten
      item tool, the quality of drug information provided by EPR software to support
      the appropriateness of prescriptions and to propose a list of quality standards
      for this type of application. METHODS: The eight EPR programmes most used in
      general practice in Italy were assessed by a multidisciplinary team using the ten
      item tool. The tool evaluated information on single drugs and drug safety and
      information on prescription rules in force. RESULTS: Out of eight EPR programmes
      assessed, none scored more than 55% of the maximum possible score. Two achieved
      scores higher than 50%, one scored 48%, four ranged from 32% to 39% and one
      obtained 22%. Information on drug safety, such as the ability to detect
      interactions, to monitor laboratory parameters or to get updated information on
      drug safety was particularly limited. None of the eight EPR programmes contained
      drug information for patients, but two of them contained drug advertising.
      CONCLUSIONS: This project highlighted the poor quality of drug information
      provided by these EPR programmes. The ten-item tool seems suitable for assessing
      their quality. Based on this analysis, we have proposed a set of ten quality
      standards for prescribing software.

PMID- 21078234
TI  - Recording of adverse events in English general practice: analysis of data from
      electronic patient records.
AB  - BACKGROUND: Although the majority of patient contact within the UK's National
      Health Service (NHS) occurs in primary care, relatively little is known about the
      safety of care in this setting compared to the safety of hospital care.
      Measurement methods to detect iatrogenic diseases in primary care require
      extensive development. Routinely collected data have been successfully applied to
      develop patient safety indicators in secondary care. Given the availability of
      electronic health data in primary care, we explored the potential to build
      adverse event screening tools using computerised medical record systems.
      OBJECTIVE: To identify the rate and types of adverse events that might be
      recorded in primary care through routinely collected data. The findings will
      inform the development of administrative data-based indicators to screen for
      patient harm arising from primary care contact. METHOD: Descriptive analyses were
      performed on data extracted from the clinical information management systems
      (CIMS) at NHS Brent. The data were explored according to age, sex and ethnicity
      of patients. Potential or actual adverse events were identified by mapping to
      three Read code chapters. RESULTS: Records from the calendar year 2007 were
      available for 69 682 registered patients from 25 practices, consisting of 680 866
      consultations. A number of adverse events could be detected through terms
      contained in certain chapters of the Read code system. These events include
      injuries due to surgical and medical care (0.72 cases of per 1000 consultations)
      and adverse drug reactions (1.26 reactions per 1000 consultations). Patterns in
      the rate of harm among patients from different ethnic groups tended to reflect
      the proportion of the respective groups in the overall Brent population, with
      more injuries occurring among patients of white and Asian ethnicities.
      CONCLUSION: These findings suggest that there is scope to develop more accurate
      and reliable means of safety surveillance in general practice using data obtained
      from electronic patient records.

PMID- 21078235
TI  - Automated processing of electronic medical records is a reliable method of
      determining aspirin use in populations at risk for cardiovascular events.
AB  - BACKGROUND: Low-dose aspirin reduces cardiovascular risk; however, monitoring
      over-the-counter medication use relies on the time-consuming and costly manual
      review of medical records. Our objective is to validate natural language
      processing (NLP) of the electronic medical record (EMR) for extracting medication
      exposure and contraindication information. METHODS: The text of EMRs for 499
      patients with type 2 diabetes was searched using NLP for evidence of aspirin use
      and its contraindications. The results were compared to a standardised manual
      records review. RESULTS: Of the 499 patients, 351 (70%) were using aspirin and
      148 (30%) were not, according to manual review. NLP correctly identified 346 of
      the 351 aspirin-positive and 134 of the 148 aspirin-negative patients, indicating
      a sensitivity of 99% (95% CI 97-100) and specificity of 91% (95% CI 88-97). Of
      the 148 aspirin-negative patients, 66 (45%) had contraindications and 82 (55%)
      did not, according to manual review. NLP search for contraindications correctly
      identified 61 of the 66 patients with contraindications and 58 of the 82 patients
      without, yielding a sensitivity of 92% (95% CI 84-97) and a specificity of 71%
      (95% CI 60-80). CONCLUSIONS: NLP of the EMR is accurate in ascertaining
      documented aspirin use and could potentially be used for epidemiological research
      as a source of cardiovascular risk factor information.

PMID- 21078236
TI  - Complexity in practice: understanding primary care as a complex adaptive system.
AB  - BACKGROUND: This series summarises new empirical research on quality improvement
      through case studies of the implementation of clinical governance arrangements in
      two primary care organisations (PCOs). OBJECTIVE: To describe a new socio
      technical model for effective quality improvement and clinical governance.
      METHOD: The research strategy included a literature review, survey, in-depth
      interviews, participant observation and purposively sampled case studies,
      conducted within a social constructionist ontological perspective. This approach
      contextualises the origins of clinical governance and the trend towards
      collaborative partnerships and federated models of practice, enabled by
      developments in primary care informatics. RESULTS: People operating within
      multidisciplinary networks communicate with each other to determine actions that
      govern their most relevant concerns. Quality improvement in two PCOs is enabled
      through social interactions between individuals and groups with complex
      relationships; and information technology (IT) systems which make some aspects of
      the quality of care explicit. CONCLUSIONS: The results are real-world exemplars
      of the emergent properties of complex adaptive systems. Improving clinical
      governance in primary care requires both complex social interactions and
      underpinning informatics. The socio-technical lessons learned from this research
      should inform future management approaches.

PMID- 21078237
TI  - The use of Google language tools as an interpretation aid in cross-cultural
      doctor-patient interaction: a pilot study.

PMID- 21078240
TI  - Prospects for trainees from Pakistan: time to streamline the links with UK.

PMID- 21078241
TI  - Diffusion weighted MR imaging (DWI) and ADC values in endometrial carcinoma.
AB  - OBJECTIVE: To determine the sensitivity of MR imaging utilizing diffusion
      weighted imaging (DWI) in detection of endometrial cancer and to compare the
      Apparent Diffusion Coefficient (ADC) values of malignant and normal endometrium.
      STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY:
      Radiology Department, Aga Khan University Hospital Karachi, from January 2007 to
      December 2009. METHODOLOGY: Patients were defined as undergoing MRI for suspected
      endometrial malignancy, and the controls were female subjects who underwent MRI
      examination for indications other than endometrial malignancy. Studied variables
      included the signal characteristics of the endometrium and ADC values. The
      sensitivity of DWI for the detection of endometrial carcinoma was calculated
      using histopathology as the gold standard, and the ADC values of the endometrium
      in patients and controls were recorded. The mean ADC values were compared using
      two-sided t- test with significance at p < 0.05 at 95% confidence interval.
      RESULTS: Out of 52 patients, 10 had hyperintense, 40 had hypointense and 2 had
      isointense endometrium on T2 weighted imaging. On DWI, 42 patients had
      hyperintense and 10 patients had hypointense endometrium. In comparison, 40
      controls had hypointense endometrium on DWI and 12 had hyperintense endometrium.
      The mean ADC value for abnormal endometrium was 0.730+/-0.215 x10-3 mm2/sec and
      of normal endometrium was 1.265+/-0.305 x10-3 mm2/sec (p < 0.001). The
      sensitivity for detection of endometrial carcinoma on DWI was 77.77%. False
      positive cases were found to be due to secretory and hyperplastic endometrium.
      False negative findings were found in a few cases of adenocarcinoma, endometroid
      carcinoma and clear cell sarcoma. CONCLUSION: In patients with suspected
      endometrial carcinoma, MRI examination utilizing DWI was a sensitive tool in
      detecting endometrial cancers with significantly lower ADC values for carcinoma
      in general. Physiological and histopathological variants may be responsible for a
      few false results.

PMID- 21078242
TI  - Frequency and characteristic features of portal hypertensive gastropathy in
      patients with viral cirrhosis.
AB  - OBJECTIVE: To determine the frequency and specific characteristic features of
      portal hypertensive gastropathy (PHG) in cirrhosis due to viral etiology. STUDY
      DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: The Aga
      Khan University Hospital, Karachi, from June 2006 till June 2008. METHODOLOGY:
      Patients with hepatitis B and C cirrhosis were included who underwent screening
      esophago-gastroduodenoscopy (EGD) for varices. Baveno III consensus statement was
      used for diagnosing PHG on endoscopy and divided them into two subgroups i.e.
      mild and severe. Data related to platelet/spleen ratio, MELD score and Child
      Turcotte Pugh (CTP) score indicating severity of cirrhosis were recorded in all
      patients. Findings were compared by using independent sample t-test. RESULTS: Out
      of 360 patients who underwent screening EGD, 226 (62.8%) were males. Two hundred
      and eighty one (78%) had hepatitis C while 79 (22%) suffered from hepatitis B
      related cirrhosis. Three hundred patients (83.3%) had PHG while 71 (24%) had
      severe PHG. Higher proportion of esophageal varices (89.7%) was present among
      those who had PHG (p < 0.001). On univariate analysis lower platelet counts
      (117+/-55 vs. 167+/-90; p < 0.001), increased spleen size (14.1+/-2.9 cm vs. 12+/
      2.4cm; p < 0.001) were found in PHG patients as compared to those without it.
      Similarly, lower platelet/spleen ratio was noted in patients with severe PHG
      (916+/-400 vs. 1477+/-899; p < 0.001). Furthermore, on multivariate analysis CTP
      score > 8 MELD score > 12 and platelets/spleen ratio < 900 were significantly
      associated factors with severe PHG. CONCLUSION: Frequency of PHG was 83% while
      severe PHG was seen in 24% cases of viral hepatic cirrhosis. MELD score > 12, CTP
      score 3 8 and platelets/spleen ratio < 900 were significant factors of severe
      PHG.

PMID- 21078243
TI  - Palliative surgery for pancreatic carcinoma.
AB  - OBJECTIVE: To evaluate the role of palliative surgical treatment in patients with
      advanced pancreatic carcinoma. STUDY DESIGN: Case series. PLACE AND DURATION OF
      STUDY: Surgical "D" Ward of Khyber Teaching Hospital, Peshawar, from January 2005
      to January 2009. METHODOLOGY: The study included patients with pancreatic
      carcinoma admitted with advanced, unresectable carcinoma of the pancreas.
      Patients with resectable tumours and with previous history of gastric or biliary
      surgery were excluded. Palliative procedures were performed after assessment of
      the tumour and its confirmation as unresectable on ultrasound and CT scan + ERCP.
      Postoperatively all patients were referred to oncologist. Complications and
      mortality were noted. RESULTS: There were 40 patients, including 24 males and 16
      females with mean age 58.72 +/- 6.42 years. The most common procedure performed
      was triple bypass in 21 (52.50%) patients followed by choledocho-, cholecysto-,
      hepaticoand gastro-jejunostomy in various combinations. Wound infection occurred
      in 7 patients and was more common in patients with co-morbidities. Biliary
      leakage occurred in 03 patients. Postoperative cholangitis occurred in 3 patients
      while 7 patients had minor leak from the drain site. Four patients developed UTI,
      while 5 patients had signs of delayed gastric emptying. Two patients had upper
      gastrointestinal bleeding. Three patients died due to septicemia and multiple
      organs failure. Rest of the patients were discharged in stable state. The mean
      hospital stay was 8.40+/-3.48 days and median survival was 7.72+/-2.39 months.
      CONCLUSION: Surgical palliation for the advanced carcinoma pancreas can improve
      the quality of life of patients and is associated with minimum morbidity and
      mortality.

PMID- 21078244
TI  - Reconstruction of mandible by free fibular flap.
AB  - OBJECTIVE: To determine the results of using the free vascularized fibular flap
      for comprehensive reconstruction of postresection or post-traumatic mandibular
      defects. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of
      Oral and Maxillofacial Surgery, King Edward Medical University, Lahore, from
      March 2007 to June 2009. METHODOLOGY: The study group consisted of patients who
      underwent reconstruction of continuity defects of the mandible using a fibular
      vascularized free flap. Indication for mandibular resection were squamous cell
      carcinoma of the floor of the mouth and alveolar ridge in 5 cases, ameloblastome
      of the mandible in 6 cases, odontogenic keratocyst in 3 cases, defect due to fire
      arm injury in 2 cases and central giant cell granuloma of the mandible in one
      case. The type of reconstruction performed was primary reconstruction in 11
      patients and secondary in 6 patients. RESULTS: There were 17 patients including
      14 males and 3 females with mean age of 40 years. All flaps except three
      survived. One patient died due to complications related to blood transfusion. Of
      those, 2 completely failed, one due to the unfavourable recipient bed of the
      patient with fire arm injury and other due to venous thrombosis. Donor site
      morbidity was low; there was some compromise in the ankle function but none of
      the patient complaint of foot drop. Simple problems with wound healing such as
      dehiscence and delayed wound healing developed in 5 patients, which usually
      required only local antiseptic treatment. After the operation patient began oral
      feeding and walking with some aid in fourth week and became completely ambulant
      in 8 weeks. CONCLUSION: In this small series the free fibula flap was a versatile
      and reliable option for microvascular reconstruction of large mandibular defects.
      It provided a large quantity of bone, which could be easily shaped and passively
      adapt to the remaining mandible and for an implant-based prosthetic restoration.

PMID- 21078245
TI  - Current pattern of antibiotic resistance in Staphylococcus aureus clinical
      isolates and the emergence of vancomycin resistance.
AB  - OBJECTIVE: To determine the pattern of antibiotic resistance in the clinical
      isolates of Staphylococcus (S.) aureus, Methicillin Resistant S. aureus (MRSA)
      and define the possible emergence of Vancomycin resistant S. aureus (VRSA) in
      Karachi. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Essa
      Laboratories and Department of Molecular Genetics, Ziauddin Hospital, from
      January to December 2009. METHODOLOGY: Staphylococcal isolates from different
      clinical specimens, pus, urine, blood, high vaginal swab and other secretions
      received at Ziauddun laboratories and Dr.Essa laboratories were collected. The
      specimens were inoculated on blood agar, MacConkey agar and Chrom agar.
      Antibiotic susceptibility to conventional antibiotics was done by disc diffusion,
      and E-test. Methicillin resistance was tested by using Oxacillin and Methicillin
      disks and confirmed by gold standard PCR for presence of mecA gene. All MRSA
      strains were subjected in addition to Vancomycin screen agar test. RESULTS: Out
      of the 450 S. aureus isolates 174 (38.6%) were found to be MRSA. In those
      isolates, high resistance was found to Cefixime (100%) Doxicycline (100%)
      Oxacillin (96.5%) Gentamicin, (96.3%), Timethoprim/Sulfametoxazole (95.6%)
      Chloramphenicol (93%) Tobramicin (81.03%), Ofloxacin (72.4%) and Ciprofloxacin
      (63.7%). Low resistance was found to Ceftazidine (36%), Amoxicillin/Clavulanate
      (32.7%), Fosfomycin (31%), Cefroxime (24%), Amikacin (17.2%) and Meropenem (13%).
      One isolate was found to be Vancomycin resistant (MIC 32 MUg/ml). Four isolates
      had intermediate resistance, with two strains having MIC of 16MUg/ml and two
      having MIC of 8MUg/ml. These strains were also resistant to all the other tested
      antibiotics except Linezolid to which all isolates were susceptible. CONCLUSION:
      Antibiotic resistance to all the conventionally used antibiotics was high in the
      tested isolates. All the strains were susceptible to Linezolid which is an
      expensive alternative with adverse side effects. Judicious use of antibiotics
      focused on the compliance and formation of antibiotic policy guide lines is
      highly recommended.

PMID- 21078246
TI  - Outcome of Cloward technique in cervical disc prolapse.
AB  - OBJECTIVE: To determine the association of pre-operative assessment of MRI
      findings, neurological status and symptoms with postoperative Cloward surgical
      outcome in cervical disc prolapse. STUDY DESIGN: Descriptive study. PLACE AND
      DURATION OF STUDY: The Neurosurgery Department of Jinnah Postgraduate Medical
      Centre (JPMC), Karachi, from May 2008 to May 2009. METHODOLOGY: Patients
      presenting with neck pain, brachialgia, limb weakness and spasticity were
      clinically examined for pre-operative neurological status of power, reflexes and
      sensation. The exclusion criteria were, cervical disc prolapsed patients, planned
      for smith-Robinson and micro-discectomy, traumatic cervical disc prolapse and
      cervical spondylosis. Neuroradiological investigations included cervical spine X
      rays and MRI. All patients were surgically treated for cervical prolapsed
      intervertebral disc with anterior cervical discectomy and interbody fusion with
      Cloward technique. Postoperative neck immobilization was done with cervical
      collar for 7-8 weeks. Drain was removed on first postoperative day while check
      plain cervical X-rays were taken on third day. Results were analysed using chi
      square test with significance at p < 0.05. RESULTS: There were 30 patients
      including, 27 (90%) males and 03 (10%) females with mean age of 44.3 years. The
      commonest symptom was neck pain. The duration of symptoms ranges from 2 to 6
      months. On MRI, prevalent levels of cervical disc prolapse were C 5-6 (43.3%) and
      C 6-7 (23.3%); 26 (86.6%) patients had disc herniation causing thecal effacement
      with cord compression and 04 (13.3%) patients showed ischemia of cord. Single
      level Cloward surgery done in 26 (86.3%) patients while two-level Cloward surgery
      performed in 04 (13.3%) only. About 83.3% patients improved and 13.3% did not
      while 01 patient was re-operated. No complications and mortality was related to
      the surgical procedure. Statistically different variables identified, related to
      outcome were pre-operative neurological status (p=0.001) and spinal cord
      involvement on MRI (p=0.001). CONCLUSION: Cloward technique for cervical disc
      prolase was simple and safe surgical procedure with favourable results and few
      complications; 100% fusion occurred after Cloward surgery, even without
      instrumentation. Outcome was significantly affected by pre-operative neurological
      status and cord involvement.

PMID- 21078247
TI  - Intracranial cavernous angiomas.
AB  - OBJECTIVE: To describe the clinical presentation, diagnosis, and management of
      patients presenting with intracranial cavernous angiomas (CAs) at a tertiary care
      hospital in Pakistan. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY:
      Section of Neurosurgery, The Aga Khan University Hospital (AKUH), Karachi, from
      January 1990 to September 2008. METHODOLOGY: A retrospective case note review of
      all patients diagnosed with intracranial CAs at AKUH during the study period. The
      studied variables included patient demographics, clinical presentation, family
      history of intracranial CAs or other space occupying lesions, modality of
      diagnosis, management, and outcome. Results were described as frequency
      percentages. RESULTS: During the review period, 18 patients (11 males and 7
      females) were diagnosed with intracranial CAs. The median age at diagnosis was
      28.5 years. The most common location of malformations was cerebrum (n=13)
      followed by brain stem (n=3), and cerebellum (n=2). Nine patients had multiple
      lesions. Family history was present in 2 patients. Seizures and focal neurologic
      deficits were the main clinical manifestations. The detection rate was 93.8% with
      magnetic resonance imaging, but less with angiography and computerized
      tomography. Ten cases were treated surgically; 8 were managed conservatively. The
      outcome was satisfactory except for one patient, who died within 6 months of
      diagnosis. Surgery was performed for gross haemorrhage, rapidly increasing
      neurologic deficits, and intractable or long-standing seizures. CONCLUSION:
      Cavernomas tend to occur at younger age in females than males. This data raises a
      possibility of a higher frequency of multiple cavernomas in Pakistani patients.
      The main clinical manifestations are seizures and focal neurologic deficits. MRI
      is most sensitive and specific neuroradiologic modality for detecting this
      vascular malformation.

PMID- 21078248
TI  - Risk factors in early pregnancy complications.
AB  - OBJECTIVE: To determine the underlying risk factors in early pregnancy
      complications and outcome. STUDY DESIGN: Case series. PLACE AND DURATION OF
      STUDY: This study was conducted at the Department of Obstetrics and Gynaecology
      Unit-IV, Liaquat University of Medical and Health Sciences, Jamshoro, from July
      2007 to June 2008. METHODOLOGY: All the women with first trimester pregnancy with
      different complications were included in this study while those women with
      uneventful first trimester were excluded. The inducted women were registered on
      pre-designed proforma. Studied variables including demographic details,
      gestational period, type of complications, risk factors, treatment and outcome.
      The data was expressed in terms of mean and percentages with a confidence
      interval of 95%. Analysis was done on SPSS version 14. RESULTS: Out of a 204
      total admissions, 115 (56.37%) patients had different early pregnancy
      complications. Their mean age was 29.4+6.8 years. Commonest complications found
      were abortion in 88 (76.52%) cases. The underlying risk factors found in abortion
      were antiphospholipid syndrome in 5 (5.68%) cases, Diabetes mellitus in 8 (9.09%)
      cases, hypertension in 16 (18.18%) cases, and polycystic ovarian syndrome and
      infection in 11 (12.5%) cases each. Most of the cases 69 (60%) were treated by
      minor surgical procedures, and 22 (19.13%) cases responded with conservative
      medical therapy. Outcome were anaemia in 92 (79.3%) cases, psychological upset in
      72 (62.1%), infection in 55 (44%) cases and coagulopathy in 9 (7.8%) cases.
      CONCLUSION: Abortion was found as the most frequent early pregnancy complication
      and the most frequent underlying risk factor was hypertension. Outcome included
      anaemia, psychological upset and infection.

PMID- 21078249
TI  - Evaluation of paclitaxel and carboplatin versus combination chemotherapy with
      fluorouracil, doxorubicin and cyclophosphamide as a neoadjuvant therapy in
      patients with inoperable breast cancer.
AB  - OBJECTIVE: To compare the results of patients with locally advanced breast cancer
      receiving two different regimens Fluorouracil, Doxorubicin and Cyclophosphamide
      (FAC) and Paclitaxel and Carboplatin. STUDY DESIGN: Comparative study. PLACE AND
      DURATION OF STUDY: The Oncology Department, Institute of Nuclear Medicine and
      Oncology (INMOL), Lahore, from March 2007 to September 2008. METHODOLOGY:
      Patients with inoperable locally advanced breast cancer of stage were included.
      Sixteen patients were given FAC regimen and 9 patients were given Paclitaxel and
      Carboplatin, each combination was cycled after 21 days for four times. Before
      enrollment, detailed medical histories, physical examinations and performance
      status assessments were done as well as postchemotherapy evaluation with regular
      follow-up visits was done. Complete Response (CR, -100%) is defined as the
      disappearance of all known disease parameter i.e. disappearance in detectable
      tumour size, node free disease and surgery is possible. Partial Response (PR, - >
      50%) was defined by 50% or greater decrease in the sum of the areas of
      bidimensionally measured lesions i.e. change of N2 to N1 or no status and some
      surgical procedure is possible to downstage the disease. Minor Response (MR) was
      defined as a decrease in the tumour insufficient to quality for partial response.
      Static disease or no evaluable reflected no significant change in disease and no
      evidence of new disease. Progression of disease (> 25%) was defined as a 25% or
      greater increase in the area of any lesion > 2 cm or in the sum of the products
      of the individual lesions or the appearance of new malignant lesions, surgery not
      possible. RESULTS: Twenty five patients completed neoadjuvant chemotherapy.
      Sixteen (66%) patients received FAC and 9 (37%) patients received PC
      chemotherapy. Overall CR (breast and axilla) was 54%, PR was 16% and minor
      response (MR) was 8%. FAC treatment induced more emesis, mucositis, alopecia and
      cardiotoxicity. No death occurred. CONCLUSION: The Paclitaxel and Carboplatin
      regimen was better tolerated; both regimens were effective in improving disease
      and overall survival.

PMID- 21078250
TI  - Joint laxity and hypermobility in adults at an industrial area of Karachi.
AB  - OBJECTIVE: To determine the frequency of joint laxity and hypermobility in adults
      at Industrial area of Karachi. STUDY DESIGN: An observational survey. PLACE AND
      DURATION OF STUDY: The Department of Medicine, Jinnah Medical College Hospital,
      Karachi, from September to December 2008. METHODOLOGY: Adults between the ages of
      14-60 years presenting in the consultant OPD for different medical conditions
      were included and examined for joint laxity and hypermobility according to
      Beighton's score. A structured proforma was designed to record all information.
      Chi-square test was used to determine the statistical significance between two
      categorical variables. P-value of < 0.05 was considered as significant. RESULTS:
      Out of 1000 adults, 717 (71.7%) were males and 283 (28.3%) were females. Seventy
      (7%) adults had joint hypermobility including 48 (68.57%) males and 22 (31.43%)
      females. A total of 54 (77.1%) patients were found to have joint laxity; this
      included 75.9% males and 24.1% females, while 16 (22.9%) cases were having joint
      hypermobility including 43.7% males and 52.3% females. The Beighton score found
      higher in females than in males (p < 0.04). Family history of joint hypermobility
      was positive in 28 (40%) of the affected individuals. Individuals aged younger
      than 26 years scored higher than those aged above. CONCLUSION: Joint laxity and
      hypermobility was not an uncommon rheumatological entity in the study group. It
      was significantly greater in females in terms of Beighton's score.

PMID- 21078251
TI  - Churg-Strauss syndrome: a rare systemic vasculitis.
AB  - Churg-Strauss syndrome is a rare diffuse small/medium sized vessel vasculitis
      that is almost invariably accompanied by severe asthma. The cause is unknown, but
      its characteristic histological findings and association with asthma distinguish
      it from other vasculitides. We report here a middle aged lady who presented with
      sudden onset of vasculitic skin lesions in association with long standing asthma.
      Skin biopsy and serology revealed diagnosis of Churg-Strauss syndrome. She was
      successfully managed with oral prednisolone.

PMID- 21078252
TI  - Transanal small bowel evisceration following digital reduction of a chronically
      prolapsing rectum.
AB  - Evisceration of the small bowel through a rectal perforation is rare. This is the
      case of a 66 year-old female presenting to the Accident and Emergency Department
      with transanal evisceration of her small bowel resulting from attempted digital
      reduction and subsequent tear of her chronically prolapsing rectum. Reduction of
      the prolapsed small bowel and primary repair of the rectal tear were carried out
      at laparotomy. The management of this case is discussed.

PMID- 21078253
TI  - Abdominal wall abscess following laparoscopic cholecystectomy: an unusual late
      complication of lost gallstones.
AB  - Laparoscopic cholecystectomy (LC) is associated with a significant risk of
      gallbladder perforation with spillage of bile and stones into the peritoneal
      cavity. The retrieval of the spilled stones is not always possible by
      laparoscopic technique. Majority of these cases do not have any problem in future
      but sometimes the lost stones lead to serious complications. The authors present
      a case of lost gallstones, which resulted into an abdominal wall abscess and
      discharging sinus 9 years after LC. This late presentation is among the very few
      reports after LC. Risk factors for gallbladder perforation, various techniques to
      avoid spillage of stones, possible complications and their management is
      discussed.

PMID- 21078254
TI  - Triplication of gallbladder.
AB  - Triplication of gallbladder is a very rare congenital anamoly of biliary tract
      and is unlikely to be revealed unless there are associated symptoms. The modern
      imaging techniques usually fail to define the exact anatomy. Pre-operative
      awareness of this anatomic variation can minimize the chances of any damage to
      the biliary tract. This case report describes a patient with cholelithiasis
      diagnosed to have double gallbladder on pre-operative ultrasound.

PMID- 21078255
TI  - Extended-spectrum beta-lactamase production in Shigella flexneri.
AB  - Emergence of multidrug-resistant strains of Shigella is a growing concern across
      the globe. Third-generation cephalosporins are used for treating infections
      caused by multidrug-resistant Shigellae. However, resistance to these
      cephalosporin antibiotics due to extended-spectrum beta-lactamases, has emerged
      as a new problem. So far extended-spectrum beta-lactamases producing Shigella has
      not been reported from Pakistan. We report such a case in Shigella flexneri from
      an 8-year old girl with acute dysentery.

PMID- 21078256
TI  - Split hand/split foot deformity with focal dermal hypoplasia (Goltz syndrome).
AB  - We report on a-6-months-old girl who manifested the phenotypic features of focal
      dermal hypoplasia. Significant limb deformities in connection with typical skin
      changes were documented. The family history had a high frequency of spontaneous
      abortions and male stillbirths. Male stillbirths are a landmark in favour of X
      linked dominant pattern of inheritance. Despite the severe hand/foot deformities,
      the skull base and the tubular bones were sclerotic.

PMID- 21078258
TI  - Diagnostic accuracy of fine needle aspiration cytology in hepatic tumours.

PMID- 21078257
TI  - Chronic gastritis and Helicobacter pylori: a histopathological study of gastric
      mucosal biopsies.
AB  - The aim of this study was to observe the histological features of chronic
      gastritis and associated effects due to Helicobacter pylori infection in 176
      randomly selected antral biopsy specimens of chronic gastritis cases. The
      specimens were reviewed for the presence or absence of H.pylori. The activity
      (neutrophilic infiltration) of gastritis and the presence or absence of mucosa
      associated lymphoid tissue (MALT) were also noted. Chi-square test (Pearson
      value) was used to analyze categorical variables. H.pylori was detected in 110
      (62.5%) cases of chronic gastritis. There was a significant association between
      H.pylori infection and activity of chronic gastritis (p=0.002). Lymphoid
      aggregates were significantly more frequently noted in H.pylori-positive patients
      (68.2%) vs. H.pylori negative group (47%), (p=0.005). It is concluded that
      H.pylori is significantly associated with active chronic gastritis and with
      formation of mucosa-associated lymphoid tissue (MALT), which may develop into
      gastric lymphoma (MALT type).

PMID- 21078259
TI  - Burn therapy for pain.

PMID- 21078262
TI  - Inflammation and cancer: tumor initiation, progression and metastasis, and
      Chinese botanical medicines.
AB  - Both historically and contemporarily, cancer is seen as an inflammatory process.
      Evidence has emerged in the last two decades that at the molecular level most
      chronic diseases, including cancer, are caused by a dysregulated inflammatory
      response. The identification of transcription factors such as nuclear factor
      kappa B and signal transducer and activator of transcription 3 and their gene
      products such as tumor necrosis factor, interleukin-1, interleukin-6, chemokines,
      cyclooxygenase-2, and vascular endothelial growth factor, adhesion molecules and
      others has provided the molecular basis for the role of inflammation in cancer.
      Tumor initiation, its progression and metastasis and the failure of immune
      suppression of tumors all can be attributed in part to chronic and systemic
      inflammation. Chinese herbs have a long history in both treatment of cancer and
      suppression of inflammation. This paper looks at recent research on cancer and
      inflammation and Chinese herbs and compounds, which can be used in the treatment
      of cancer.

PMID- 21078263
TI  - [A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect
      in treatment of depression].
AB  - Clinical and experimental studies show that the onset of effect of acupuncture on
      depression is more rapid than selective serotonin reuptake inhibitors, a class of
      antidepressants. Acupuncture treatment is characterized by controlling anxiety
      and gastrointestinal discomfort. The onset time of acupuncture treatment for
      various pains is a week or so, which is the same as the rapid onset time of
      antidepressant effect of acupuncture, and the main pathway of acupuncture
      analgesia is through endogenous opioid system. Opioid peptides can produce
      pleasure, and decrease anxiety and gastrointestinal discomfort, so opioid
      peptides are considered to have antidepressant effect. Accordingly, the main
      pathway of acupuncture analgesia-the endogenous opioid system, is considered a
      mechanism for rapid onset of acupuncture effects on depression.

PMID- 21078264
TI  - [Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients
      with polycystic ovary syndrome].
AB  - Traditional Chinese medicine (TCM) usually views polycystic ovary syndrome (PCOS)
      as a menstrual disease or infertility disease. Reproductive dysfunction in PCOS
      is characterized by ovarian androgen excess and disturbance of follicular
      development, and its main clinical manifestations include delayed menstruation,
      scant menstruation, amenorrhea or infertility. Insulin resistance is a key
      pathological mechanism of PCOS. "Tiangui" (kidney essence) as a sex-stimulating
      essence in female in TCM theory, is essential to the menstruation and pregnancy
      of women. The disturbance of Tiangui (including time, status and rhythm) would
      result in female reproductive problems. Current studies of Tiangui indicate that
      ovary is the target organ of PCOS treatment, and its functional characteristics
      are consistent with the properties of Tiangui in time frame, state form and
      rhythm cycle. It is then concluded that ovarian dysfunction in PCOS can be
      expressed as disorder of Tiangui.

PMID- 21078265
TI  - [Logistic regression analysis on relationships between traditional Chinese
      medicine constitutional types and overweight or obesity].
AB  - OBJECTIVE: To explore the relationships between traditional Chinese medicine
      (TCM) constitutional types and overweight or obesity so as to provide evidence
      for adjusting constitutional bias and preventing and treating obesity. METHODS:
      The data comes from a cross-sectional survey on TCM constitution of 18 805
      samples aged above 18 in Beijing and 8 provinces (Jiangsu, Anhui, Gansu, Qinghai,
      Fujian, Jilin, Jiangxi and Henan) in China. The survey of TCM constitution was
      performed by standardized constitution in Chinese medicine questionnaire (CCMQ).
      Discriminatory analysis method was used to judge the individual's constitutional
      type (gentleness type, qi-deficiency type, yang-deficiency type, yin-deficiency
      type, phlegm-dampness type, dampness-heat type, blood-stasis type, qi-depression
      type and special diathesis type). The relationships between TCM constitution
      types and overweight or obesity was investigated by logistic regression analysis.
      RESULTS: Compared with gentleness type, the risk of overweight (OR, 2.05; 95% CI,
      1.79-2.35) and obesity (OR, 4.34; 95% CI, 3.52-5.36) in phlegm-dampness type is
      significantly increased; the risk of obesity (OR, 1.60; 95% CI, 1.30-1.98) in qi
      deficiency type is significantly higher; the risk of overweight and obesity in
      yang-deficiency type, blood-stasis type, and qi-depression type is significantly
      lower. CONCLUSION: Phlegm-dampness type and qi-deficiency type are the main
      constitutional risk factors of overweight or obesity.

PMID- 21078266
TI  - [Effects of oxymatrine injection combined with low-dose paclitaxel on mRNA and
      protein expressions of vascular endothelial growth factor and CXC chemokine
      receptor 4 in human gastric carcinoma SGC-7901 cells].
AB  - OBJECTIVE: To investigate the effects of oxymatrine injection (OI) combined with
      low-dose paclitaxel on expressions of mRNAs and proteins of vascular endothelial
      growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4) in human gastric
      carcinoma SGC-7901 cells. METHODS: Methyl thiazolyl tetrazolium assay was used to
      examine the effects of OI combined with low-dose paclitaxel on proliferation of
      SGC-7901 cells. Real-time reverse transcription-polymerase chain reaction,
      immunofluorescence and enzyme-linked immunosorbent assay were employed to measure
      the expressions of VEGF and CXCR4 mRNAs and proteins in gastric carcinoma SGC
      7901 cells respectively. RESULTS: Except that 20 MUg/mL paclitaxel had no
      influence on expression of VEGF mRNA in SGC-7901 cells (P>0.05), 40 MUg/mL OI or
      low-dose paclitaxel (20 MUg/mL) inhibited the proliferation of SGC-7901 cells and
      reduced the expressions of VEGF and CXCR4 mRNAs and proteins in SGC-7901 cells
      (P<0.01). The expressions of VEGF and CXCR4 mRNAs and proteins in the OI plus low
      dose paclitaxel group were markedly lower than those in the low-dose paclitaxel
      group (P<0.01). CONCLUSION: OI combined with low-dose paclitaxel can inhibit VEGF
      and CXCR4 of gastric carcinoma SGC-7901 cells markedly, which may be one of its
      mechanisms of anti-angiogenic ability.

PMID- 21078267
TI  - [Application and evaluation of a pseudotyped virus assay for screening herbs for
      anti-H5N1 avian influenza virus].
AB  - OBJECTIVE: To establish a method based on a pseudotyped virus assay for screening
      drugs for anti-H5N1 avian influenza virus, and then to evaluate anti-virus
      activity of traditional Chinese herbal compounds with the function of purgation,
      detoxification, cooling the blood and reinforcing the healthy qi based on
      seropharmacology. METHODS: Pseudotyped viruses expressing H5N1 virus
      hemagglutinin were constructed. Herb-medicated sera were prepared by feeding
      Wistar rats traditional Chinese herbal compounds. Then inhibitory effects of
      different drug-medicated sera against pseudotyped virus were evaluated based on
      incubating serum with pseudotyped viruses or target cells such as Madin-Darby
      canine kidney cells and human embryonic kidney cell line 293T cells, and the
      expression of hemagglutinin (HA) protein was detected by flow cytometry. RESULTS:
      Pseudotyped virus could be neutralized by specific 2B4 monoclonal antibody at
      doses of 50 MUL (500 MUg), 25 MUL (250 MUg) and 12.5 MUL (125 MUg), which showed
      that it was a feasible assay to screen drugs. No significant difference was
      observed in inhibition against H5N1 pseudotyped virus between herb-medicated sera
      and control serum (P>0.05), meanwhile, the herb-medicated sera also could not
      inhibit HA expression. CONCLUSION: Pseudotyped virus assay is a safe, effective,
      and exact method for screening anti-H5N1 avian influenza virus herbs, and herb
      medicated sera prepared by administration of herbs with the function of
      purgation, detoxification, cooling the blood and reinforcing the healthy qi do
      not contain active ingredient or monomer which can inhibit HA and sialic acid
      alpha 2,3-galatose.

PMID- 21078268
TI  - [Collagen protein expressions in ischemic myocardium of rats with acute
      myocardial infarction and effects of qi-tonifying, yin-tonifying and blood
      activating herbs and detoxifying and blood-activating herbs].
AB  - OBJECTIVE: To investigate collagen protein expressions in ischemic myocardium of
      rats with acute myocardial infarction (AMI) and the effects of qi-tonifying, yin
      tonifying and blood-activating herbs and detoxifying and blood-activating herbs.
      METHODS: AMI model of Wistar rat was established by ligating left anterior
      descending coronary artery. The model rats were randomly divided into untreated
      group, perindopril group (0.36 mg/kg), Yiqi Yangyin Huoxue (YQYYHX) group
      (Shengmai Capsule 0.24 g/kg and Compound Chuanxiong Capsule 0.40 g/kg), and Jiedu
      Huoxue (JDHX) group (Compound Chuanxiong Capsule 0.40 g/kg and berberine 0.16
      g/kg), with 10 rats in each group. The latter three groups were treated with
      corresponding drugs by gastric gavage once a day for 4 weeks after modeling. Sham
      operated (puncture without ligation) group and normal control group with 10 rats
      in each group were given normal saline by gastric gavage. Left ventricular mass
      index (LVMI) was measured, and pathologic changes in myocardium were observed by
      hematoxylin-eosin staining 4 weeks later. Contents of procollagen type III and
      collagen type IV in serum were measured by radioimmunoassay, and expressions of
      collagen types I and III in ischemic myocardium were measured by
      immunohistochemical methods. RESULTS: Compared with rats in the sham-operated
      group, weight of left ventricle and LVMI of rats in the model group increased
      significantly; content of procollagen type III in serum increased; contents of
      collagen types I and III in ischemic myocardium increased significantly (P<0.01).
      Compared with rats in the untreated group, LVMI and content of procollagen type
      III in serum of rats treated with herbs decreased significantly, and expressions
      of collagen types I and III in ischemic myocardium were inhibited (P<0.05,
      P<0.01). The effect of detoxifying and blood-activating herbs on collagen type
      III in ischemic myocardium is better than perindopril. CONCLUSION: Both qi
      tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood
      activating herbs have beneficial effects on rats with AMI in decreasing LVMI and
      procollagen type III content, and inhibiting expressions of collagen types I and
      III in ischemic myocardium, thus protecting ischemic myocardium after AMI. It may
      explain the machanism of Chinese herbal medicine inhibiting ventricular
      remodeling after AMI.

PMID- 21078269
TI  - [Senescence-inducing effects of Chinese herbal medicine Tenglong Buzhong
      Decoction on human colon carcinoma LS-174-T cells and the mechanism].
AB  - OBJECTIVE: Cell senescence is an important anti-cancer mechanism and may
      contribute to cancer therapeutic outcome. The present study observed the effects
      of Tenglong Buzhong Decoction (TLBZD), a Chinese herbal formula, on senescence in
      human colon carcinoma LS-174-T cells. METHODS: LS-174-T cells were treated with
      TLBZD, and morphology change was observed under a microscope. Cell senescence was
      identified by senescence-associated beta-galactosidase (SA-beta-gal) staining,
      and cell cycle was analyzed by flow cytometry. Expressions of p53,
      p21(WAF1/CIP1), p16 and RB and RB phosphorylation were detected by Western blot.
      RESULTS: After being treated with TLBZD, LS-174-T cells became enlarged and
      flattened by morphology; SA-beta-gal staining was positive and cell cycle was
      arrested in G0/G1. In addition, up-regulations of p21(WAF1/CIP1) and p16, as well
      as inhibition of RB phosphorylation were detected in response to TLBZD treatment.
      Expressions of p53 and RB were unchanged after TLBZD treatment. CONCLUSION: TLBZD
      is effective in inducing cell senescence in human colon carcinoma LS-174-T cells,
      which may relate to up-regulations of p21(WAF1/CIP1) and p16 and inhibition of RB
      phosphorylation.

PMID- 21078270
TI  - [Effects of Chinese herbal medicine Bushen Gubiao Recipe on toll-like receptor 4
      and CD4(+)CD25(+)foxp3(+) regulatory T cells in mice with recurrent respiratory
      tract infections].
AB  - OBJECTIVE: To evaluate the effects of Bushen Gubiao Recipe (BGR), a compound
      traditional Chinese herbal medicine, on toll-like receptor 4 (TLR4) signaling
      pathway and CD4(+)CD25(+)foxp3(+)regulatory T cells (CD4(+)CD25(+)foxp3(+)Tregs)
      in mice with recurrent respiratory tract infections (RRTIs). METHODS: A mouse
      model of kidney-yang deficiency which simulated physical characteristics of RRTIs
      was established by intraperitoneal injection of hydrocortisone for 14 d. The
      model mice were divided into 4 groups, model group, high-dose BGR group, low-dose
      BGR group, and nucleic acid and casein oral solution group. They were
      administered respectively with distilled water, high-dose BGR (50 g/kg body
      weight), low-dose BGR (25 g/kg body weight) and nucleic acid and casein oral
      solution. Besides, a normal control group was set up and gastrogavage with
      distilled water. The effect of intervention was evaluated 4 weeks later by
      estimating the changes in behaviors of mice. Expressions of TLR4 and nuclear
      factor-kappa B (NF-kappaB) p65 in lung tissue were detected by
      immunohistochemical SABC method, the expression of TLR4 mRNA in lung tissue was
      detected by fluorescence quantitative-polymerase chain reaction (FQ-PCR), and the
      level of blood CD4(+)CD25(+)foxp3(+) Tregs was determined by flow cytometry.
      RESULTS: A kidney-yang deficiency mouse model with RRTIs was successfully
      established by intraperitoneal injection of hydrocortisone. BGR could improve the
      abnormal behavioral condition of the mice and enhance the expressions of TLR4 and
      NF-kappaB p65 in the lung tissue. Expression of TLR4 mRNA in high-dose BGR group
      was higher than that in model group (P<0.05), while the difference was not
      statistically significant between high-dose BGR group and low-dose BGR group
      (P>0.05). Levels of CD4(+)CD25(+)foxp3(+)Tregs in high-dose BGR group and nucleic
      acid and casein oral solution group were lower than that in model group (P<0.05),
      while the difference was not statistically significant between high-dose BGR
      group and low-dose BGR group (P>0.05). CONCLUSION: BGR can improve the behavior
      of the kidney-yang deficiency mice, and improve the innate immune function by up
      regulating TLR/NF-kappaB signaling pathway. BGR can adjust the immune imbalance
      of T-helper cell (Th) 1/Th2 through reducing the activity of
      CD4(+)CD25(+)foxp3(+)Tregs and enhancing the immune response of Th1 type.

PMID- 21078271
TI  - [Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions
      and activities of matrix metalloproteinases in human skin fibroblasts and human
      leukemia cell line THP-1].
AB  - OBJECTIVE: In order to reveal the treatment mechanism of Chinese medicine with
      the effect of activating blood and resolving putridity, we selected acetyl-11
      keto-beta-boswellic acid (AKBA) and arsenic trioxide (ATO), the main monomeric
      components of frankincense and arsenolite which are two most commonly used
      Chinese medicine with effect of activating blood and resolving putridity. We
      combined AKBA and ATO as a compound, and explored its regulatory role in
      productions and activities of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9
      in human skin fibroblasts (HSFbs) and human acute monocytic leukemia cell line
      THP-1 in inflammatory state. METHODS: In order to simulate the inflammatory micro
      environment of chronic wounds, we established 3 cell models: HSFb model activated
      by tumor necrosis factor-alpha (TNF-alpha), THP-1 cell model activated by phorbol
      12-myristate-13-acetate (PMA) and HSFb-THP-1 cell coculture system. AKBA and ATO
      were cocultured with these cell models. Enzyme-linked immunosorbent assay
      (ELISA), gelatin zymography assay and reverse transcription-polymerase chain
      reaction (RT-PCR) were used to test the secretions, activities and mRNA
      expressions of MMP-1, MMP-2 and MMP-9. In the study of the regulatory mechanism
      of AKBA and ATO on MMPs, AKBA and ATO were cocultured with the cell models. ELISA
      was used to test the secretions of TNF-alpha and interleukin-1beta (IL-beta) and
      Western blot was used to test the phosphorylation levels of extracellular signal
      regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated proteinkinase
      (p38MAPK). RESULTS: Compound of AKBA and ATO inhibited MMP-1, MMP-2 and MMP-9
      mRNA expressions, secretions and activities respectively in HSFbs and THP-1 cells
      in inflammatory state (P<0.05, P<0.01). Also compound of AKBA and ATO inhibited
      secretions of TNF-alpha and IL-1beta in THP-1 cells and cell coculture system
      (P<0.01). It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFbs
      and THP-1 cells (P<0.05, P<0.01). CONCLUSION: The combined use of AKBA and ATO
      which in line with the rule of activating blood and resolving putridity inhibits
      fibroblasts and inflammatory cells in producing MMPs in inflammatory state
      through inhibiting the release of inflammatory factors and MAPK cascade pathway.

PMID- 21078272
TI  - [Effects of Shenmai Injection on serum concentration and pharmacokinetics of
      digoxin in dogs with heart failure].
AB  - OBJECTIVE: To explore the effects of Shenmai Injection (SMI), a compound
      traditional Chinese herbal medicine, on pharmacokinetics and serum concentration
      of digoxin when applied together with digoxin. METHODS: Twenty dogs with heart
      failure were randomly divided into 4 groups: control group and low-, medium- and
      high-dose SMI groups, with 5 dogs in each group. After intravenous injection of
      digoxin injection at a dose of 7.41 MUg/kg, dogs in the control group were
      administered intravenously with normal saline 20 mL daily for 5 d, and the other
      groups were intravenously administered with SMI at the doses of 0.517, 1.034 and
      1.551 mL/kg respectively. After the administration, the blood was collected at
      designed time points. Serum concentration of digoxin was determined by high
      performance liquid chromatography with electrospray tandem mass spectrometry
      (HPLC/MS/MS). RESULTS: The low-, medium- and high-dose SMI showed different
      effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI
      revealed a tendency to decrease the elimination half-life (T(1/2beta)) of
      digoxin. The low-dose SMI showed a tendency to decrease the digoxin
      concentration. Serum clearance (CL) in the low-dose SMI group was higher than
      that in the control, and also significantly higher than those in the medium- and
      high-dose SMI groups (P<0.05). The area under concentration-time curve (AUC(0
      >infinity)) in the low-dose SMI group was lower than that in the control group
      (P=0.05); the AUC(0->72 h) and AUC(0->infinity) in the low-dose SMI group were
      significantly lower than those in the medium- and high-dose SMI groups. Low-dose
      SMI accelerated the clearance of digoxin in blood. CONCLUSION: Low-, medium- and
      high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals
      a tendency to shorten T(1/2beta) of digoxin. Low-dose SMI can accelerate the
      clearance of digoxin in blood.

PMID- 21078273
TI  - [Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters
      in hippocampus of rats with postpartum depression].
AB  - OBJECTIVE: To investigate the effects of Xiaoyao Powder, a compound traditional
      Chinese herbal medicine for treatment of depression, on monoamine
      neurotransmitters in hippocampus of rats with postpartum depression (PPD).
      METHODS: Ovariectomized Sprague-Dawley rats were randomly divided into 4 groups:
      control group, untreated group, fluoxetine hydrochloride group and Xiaoyao Powder
      group. Except for the control group, the rats in the other 3 groups were injected
      subcutaneously with estrogen for 23 successive days to induce the "pregnancy"
      state. In the next 30 successive days, rats were given test drugs respectively
      and the concentrations of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine
      (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: PPD was induced in rats of
      untreated group, and compared with rats of control group, the concentrations of
      NE, DA and 5-HT in the hippocampus significantly reduced (P<0.01), while the
      concentration of 5-HIAA significantly increased (P<0.01). Xiaoyao Powder
      treatment significantly improved the behavior indexes and levels of monoamine
      neurotransmitters in hippocampus (P<0.01). Xiaoyao Powder and fluoxetine
      hydrochloride produced similar effects in rats with PPD. CONCLUSION: Xiaoyao
      Powder produces an antidepression effect in rats by regulating the levels of
      monoamine neurotransmitters in hippocampus.

PMID- 21078274
TI  - [Diagnosis and treatment rule of traditional Chinese medicine for syndrome
      factors of chronic congestive heart failure: a study based on Shannon entropy
      method].
AB  - OBJECTIVE: The primary aim of this research is to systematically sort out and
      analyze available clinical documents for chronic congestive heart failure in
      traditional Chinese medicine (TCM) and integrated traditional Chinese and Western
      medicine, and to explore the diagnosis and treatment rule of TCM syndrome factors
      with data mining method. METHODS: Based on the China National Knowledge Internet
      (CNKI) and Chinese Biomedical Literature Database (CBM), using "chronic heart
      failure" or "chronic congestive heart failure" or "chronic cardiac insufficiency"
      and "traditional Chinese medicine" or "syndrome" or "integrated traditional
      Chinese and Western medicine" as keywords for literature selection, we used
      Shannon entropy nonlinear complex system method for the feature extraction after
      data preprocessing. RESULTS: The statistics showed that yang deficiency, qi
      deficiency, blood stasis, water retention, yin deficiency, and turbid phlegm were
      principal TCM syndrome factors; herbs of qi-tonifying, blood-activating, water
      draining, phlegm-dispelling, exterior-releasing, interior-warming were main drugs
      for clinical application. The symptoms and Chinese herbs which intimately connect
      with TCM syndrome factors were extracted, while their diagnostic contribution
      degrees were quantified by correlation coefficient. The symptoms which had high
      scores were general syndromes while the symptoms which had low scores were
      specific manifestations of a certain patient. Common Chinese herbs corresponding
      to each syndrome factor were picked out, indirectly reflecting their frequencies
      in clinical application. CONCLUSION: Based on data mining of the relationship
      among the four diagnostic methods of TCM, syndrome factors and herbs, this study
      provided references for differentiation of TCM syndrome and selection of Chinese
      medicine according to clinical syndrome factors.

PMID- 21078275
TI  - Statistical inference and experimental design of univariate qualitative data of
      single-group design.

PMID- 21078276
TI  - [A discussion of English translation of 1995 and 1997 Chinese National Standards
      of Traditional Chinese Medical Terminologies for Clinical Diagnosis and
      Treatment].

PMID- 21078277
TI  - [A study on translation of ellipses in Huangdi Neijing from perspective of
      hermeneutic theory].

PMID- 21078278
TI  - Antileishmanial activity of benzocycloalkyl azole oximino ethers: the
      conformationally constraint analogues of oxiconazole.
AB  - Antileishmanial activities of 16 synthetic oximino benzocycloalkyl azoles against
      Leishmania donovani were evaluated in vitro against extracellular promastigotes
      and intracellular amastigotes. Based on SI (Selectivity Index), five compounds
      were tested further in vivo in hamster model. Out of these, three compounds have
      shown medium activity (53-58%) and one has shown significant inhibition of
      parasite multiplication (70%). Despite the fact that these compounds were better
      than the existing antileishmanials in respect to IC(50) and SI values, they were
      less active than miltefosine in vivo. The present study has helped us in
      identifying a new lead that could be exploited as a potential antileishmanial
      agent.

PMID- 21078279
TI  - Risk factors identified associated with tuberculosis in cattle at 11 livestock
      experiment stations of Punjab Pakistan.
AB  - The study was carried out in cattle kept at 11 livestock experiment stations of
      Punjab by using single comparative cervical intradermal tuberculin (SCCIT) test.
      Sahiwal was the main breed kept at these farms. Sixty three percent of animals
      were between four and 10 years of age. Seventy-six percent of animals weighed
      between 300 and 400 kg and 66% produced 5-10l of milk/day. Animals other than
      cattle were present at about 64% of these farms. The positive SCCIT test was
      recorded in 7.6% of animals at the 11 farms. However, the prevalence of
      tuberculosis varied from 2.0% to 19.3% at these farms. Bivariate frequency
      analysis showed that the chances of a positive SCCIT test were higher in older
      animals, in cattle with higher number of calving and those produced up to 1800l
      of milk. However, the chances of positive SCCIT test decreases with further
      increase in milk production. Results of bivariate and/or multivariate logistic
      regression analysis after controlling for the farm showed a significant
      association of age of cattle, numbers of calving, total milk produced, per day
      milk, lactation length, presence of sheep at the farm and total numbers of
      animals at the farm with a positive SCCIT test. It can be concluded from the
      study that herd prevalence of tuberculosis was 100%, while animal prevalence was
      about 8% at these farms. The stronger risk factors identified by logistic
      analysis were the age of cattle, numbers of calving, total milk produced and
      lactation length, while the presence of sheep at the farm has protective effect.

PMID- 21078280
TI  - Chemometric-assisted kinetic-spectrophotometric method for simultaneous
      determination of ascorbic acid, uric acid, and dopamine.
AB  - A chemometric-assisted kinetic spectrophotometric method has been developed for
      simultaneous determination of ascorbic acid (AA), uric acid (UA), and dopamine
      (DA). This method relies on the difference in the kinetic rates of the reactions
      of analytes with a common oxidizing agent, tris(1,10-phenanthroline) and
      iron(III) complex (ferritin, [Fe(phen)(3)](3+)) at pH 4.4. The changes in
      absorbance were monitored spectrophotometrically. The data obtained from the
      experiments were processed by chemometric methods of artificial neural network
      (ANN) and partial least squares (PLS). Acceptable techniques of prediction set,
      randomization t test, cross-validation, and Y randomization were applied for the
      selection of the best chemometric method. The results showed that feedforward
      artificial neural network (FFANN) is more efficient than the other chemometric
      methods. The parameters affecting the experimental conditions were optimized, and
      it was found that under optimal conditions Beer's law is followed in the
      concentration ranges of 4.3-74.1, 4.3-78.3, and 2.0-33.0 MUM for AA, UA, and DA,
      respectively. The proposed method was successfully applied to the determination
      of analytes in serum and urine samples.

PMID- 21078281
TI  - Light-chain shuffling from an antigen-biased phage pool allows 185-fold
      improvement of an anti-halofuginone single-chain variable fragment.
AB  - Halofuginone is an antiprotozoal drug used in the treatment of coccidiosis in
      poultry, a contagious enteric disease caused by parasites of the Eimeria spp. To
      ensure that food is free from any halofuginone residues and safe for human
      consumption, a rapid method to detect these residues below the maximum residue
      limits (MRLs) in a variety of matrices is necessary. To address this need, we
      constructed an immune single-chain variable fragment (scFv) library from the RNA
      of a halofuginone-immunized chicken and selected halofuginone-specific scFv by
      phage display. The best clone isolated from the library had a limit of detection
      of 30 ng/ml as determined by enzyme-linked immunosorbent assay (ELISA). However,
      the minimum MRL for halofuginone in certain foodstuffs can be as low as 1 ng/ml,
      well below the sensitivity of the selected antibody. The selected antibody was
      then affinity maturated by light-chain shuffling to further improve the
      antibody's assay performance. The halofuginone-specific heavy-chain pool of the
      biopanned library was assembled with the light-chain repertoire amplified from
      the original prepanned library. This resulted in a heavy-chain-biased library
      from which an scFv with the potential to detect halofuginone residues as low as
      80 pg/ml was isolated, a 185-fold improvement over the original scFv. This new
      chain-shuffled scFv was incorporated into a validated ELISA (according to
      Commission Regulation 2002/657/EC) for the sensitive detection of halofuginone in
      spiked processed egg samples.

PMID- 21078282
TI  - Optimization of antibody-conjugated magnetic nanoparticles for target
      preconcentration and immunoassays.
AB  - Biosensors based on antibody recognition have a wide range of monitoring
      applications that apply to clinical, environmental, homeland security, and food
      problems. In an effort to improve the limit of detection of the Naval Research
      Laboratory (NRL) Array Biosensor, magnetic nanoparticles (MNPs) were designed and
      tested using a fluorescence-based array biosensor. The MNPs were coated with the
      fluorescently labeled protein, AlexaFluor647-chicken IgG (Alexa647-chick IgG).
      Antibody-labeled MNPs (Alexa647-chick-MNPs) were used to preconcentrate the
      target via magnetic separation and as the tracer to demonstrate binding to slides
      modified with anti-chicken IgG as a capture agent. A full optimization study of
      the antibody-modified MNPs and their use in the biosensor was performed. This
      investigation looked at the Alexa647-chick-MNP composition, MNP surface
      modifications, target preconcentration conditions, and the effect that magnetic
      extraction has on the Alexa647-chick-MNP binding with the array surface. The
      results demonstrate the impact of magnetic extraction using the MNPs labeled with
      fluorescent proteins both for target preconcentration and for subsequent
      integration into immunoassays performed under flow conditions for enhanced signal
      generation.

PMID- 21078283
TI  - Analysis of two pharmacodynamic biomarkers using acoustic micro magnetic
      particles on the ViBE bioanalyzer.
AB  - Pharmacodynamic responses to drug treatment are often used to confirm drug-on
      target biological responses. Methods ranging from mass spectrometry to
      immunohistochemistry exist for such analyses. By far, the most extensively used
      methodologies employ antigen-specific antibodies for detection (at a minimum)
      and, in some cases, target quantitation as well. Using a novel frequency
      modulating technology from BioScale called acoustic micro magnetic particle
      (AMMP) detection, two pathway biomarkers were chosen for pharmacodynamic analysis
      and compared with either AlphaScreen or LI-COR Western blot assays. For these
      studies, pharmacodynamic biomarkers for both proteasome and phosphoinositol 3
      kinase inhibition were used. Our results show clearly that the BioScale
      technology is a robust and rapid method for measuring recombinant standards or
      endogenously derived proteins from both tissue culture and mouse xenograft tumor
      lysates. Moreover, the sensitivity obtained with the BioScale platform compares
      favorably with LI-COR Western blot and AlphaScreen technologies. Furthermore, the
      use of the ViBE Bioanalyzer eliminates the labor-intensive effort of Western blot
      analysis and is devoid of the optical and other endogenous interfering substances
      derived from lysates of xenograft tumors typically observed with AlphaScreen.

PMID- 21078284
TI  - Infrared study of trifluoroacetic acid unpurified synthetic peptides in aqueous
      solution: trifluoroacetic acid removal and band assignment.
AB  - Synthetic peptide or protein samples are mostly unpurified with trifluoroacetic
      acid (TFA) used during the synthesis procedure, which strongly interferes with
      structure determination by infrared (IR) spectroscopy. The aim of this work was
      to propose a simple strategy to remove TFA contribution from attenuated total
      reflection (ATR)-IR spectra of the hexahistidine peptide (His6) in aqueous
      solution to study the conformation of this synthetic peptide without previous
      purification. Such a strategy is based on the subtraction mode widely employed to
      remove water contribution, and it is tested with TFA unpurified histidine as a
      model system. The subtraction is based on eliminating the strong TFA bands at
      1147 and 1200cm(-1) by applying a scaling factor (as in buffer correction). The
      proposed modes represent excellent strategies that do not modify spectral
      features, and they provide reliable routines to obtain the synthetic peptide
      spectrum without TFA contribution. The conformational information from the
      corrected spectra at different pH values is deduced from semiempirical calculated
      IR spectra of different His6 conformers. The spectral features and the band
      positions of the corrected spectrum suggest that the peptide molecules mainly
      adopt an intermolecular beta-sheet structure.

PMID- 21078285
TI  - A capacity for mixing in capillary wells for microplates.
AB  - Sample/reagent mixing is important in microplate instrumentation and the approach
      of mixing prior to dispensation into the wells can be problematic when assays
      involve a mixture of different proportions of reagents. We demonstrate here with
      capillaries, a simple and highly effective method that uses air actuation and
      liquid surface tension to create pendant drops in which the inherent inner
      circulatory flow within accomplishes mixing. The approach portends the capability
      to be incorporated into microplates in order to provide a useful feature for
      assay investigations.

PMID- 21078286
TI  - Bicinchoninic acid (BCA) assay in low volume.
AB  - The BCA assay is a colorimetric method for estimating protein concentration. In
      96-well plates, the relationship between protein content and absorbance is nearly
      linear over a wide range; however, performance is reduced in lower volume. To
      overcome this limitation, we performed the BCA assays in opaque, white 384-well
      plates. These plates emit fluorescence between 450-600 nm when excited at 430 nm;
      thus, their fluorescence is quenched by the BCA chromophore (lambda(max) 562 nm).
      This arrangement allowed accurate determination of protein content using only 2
      MUL of sample. Moreover, soluble flourescein could replace the white plates,
      creating a homogenous format.

PMID- 21078287
TI  - Evaluation of osteoclastic resorption activity using calcium phosphate coating
      combined with labeled polyanion.
AB  - Osteoclasts are involved in bone resorption, and its activation is considered one
      of the causes of osteoporosis. The pit assay is the principal method for
      evaluating osteoclast function by measuring hydroxyapatite resorption in vitro.
      However, the pit assay requires time and trained techniques, including the pit
      image analysis, and there is no other easy method for evaluating bone resorption.
      In this study, we developed a novel approach to quantify the bone resorption
      activity using a calcium phosphate (CaP) coating labeled with fluorescent
      polyanion. Fluoresceinamine-labeled chondroitin polysulfate or Hoechst 33258
      labeled deoxyribonucleic acid was used for CaP labeling. When macrophage cell
      line RAW264 was cultured on the labeled CaP under the stimulation with the
      receptor activator of the NF-kappaB ligand (RANKL), RAW264 cells differentiated
      into osteoclastic cells and the fluorescence intensity of the culture supernatant
      and pit area increased in a time- and dose-dependent manner. Furthermore, drugs
      for osteoporosis treatment, such as pamidronate and beta-estradiol, inhibited
      fluorescein release by the cells stimulated with RANKL. A positive correlation
      between the fluorescence intensity and pit area was observed (r=0.917). These
      results indicated that this new method using fluorescent polyanion-labeled CaP is
      a standardized useful assay system for the evaluation of bone resorption
      activity.

PMID- 21078288
TI  - Improved gel electrophoresis matrix for hydrophobic protein separation and
      identification.
AB  - We propose an improved acrylamide gel for the separation of hydrophobic proteins.
      The separation strategy is based on the incorporation of N-alkylated and N,N'
      dialkylated acrylamide monomers in the gel composition in order to increase
      hydrophobic interactions between the gel matrix and the membrane proteins.
      Focusing on the most efficient monomer, N,N'-dimethylacrylamide, the potentiality
      of the new matrix was evaluated on membrane proteins of the human colon HCT-116
      cell line. Protein analysis was performed using an adapted analytical strategy
      based on FT-ICR tandem mass spectrometry. As a result of this comparative study,
      including advanced reproducibility experiments, more hydrophobic proteins were
      identified in the new gel (average GRAVY: -0.085) than in the classical gel
      (average GRAVY: -0.411). Highly hydrophobic peptides were identified reaching a
      GRAVY value up to 1.450, therefore indicating their probable locations in the
      membrane. Focusing on predicted transmembrane domains, it can be pointed out that
      27 proteins were identified in the hydrophobic gel containing up to 11
      transmembrane domains; in the classical gel, only 5 proteins containing 1
      transmembrane domain were successfully identified. For example, multiple ionic
      channels and receptors were characterized in the hydrophobic gel such as the
      sodium/potassium channel and the glutamate or the transferrin receptors whereas
      they are traditionally detected using specific enrichment techniques such as
      immunoprecipitation. In total, membrane proteins identified in the classical gel
      are well documented in the literature, while most of the membrane proteins only
      identified on the hydrophobic gel have rarely or never been described using a
      proteomic-based approach.

PMID- 21078289
TI  - Applications of phasor plots to in vitro protein studies.
AB  - In a recent article, we described the application of phasor analysis to
      fluorescence intensity decay data on in vitro samples. As detailed in that
      article, this method provides researchers with a simple graphical method for
      viewing lifetime data that can be used to quantify individual components of a
      mixture as well as to identify excited state reactions. In the current article,
      we extend the use of in vitro phasor analysis to intrinsic protein fluorescence.
      We show how alterations in the excited state properties of tryptophan residues
      are easily visualized using the phasor method. Specifically, we demonstrate that
      protein-ligand and protein-protein interactions can result in unique shifts in
      the location of phasor points, indicative of protein conformational changes.
      Application of the method to a rapid kinetic experiment is also shown. Finally,
      we show that the unfolding of lysozyme with either urea or guanidine
      hydrochloride results in different phasor trajectories, indicative of unique
      denaturation pathways.

PMID- 21078290
TI  - Applications of phasors to in vitro time-resolved fluorescence measurements.
AB  - The phasor method of treating fluorescence lifetime data provides a facile and
      convenient approach to characterize lifetime heterogeneity and to detect the
      presence of excited state reactions such as solvent relaxation and Forster
      resonance energy transfer. The method uses a plot of M sin(Phi) versus M
      cos(Phi), where M is the modulation ratio and Phi is the phase angle taken from
      frequency domain fluorometry. A principal advantage of the phasor method is that
      it provides a model-less approach to time-resolved data amenable to visual
      inspection. Although the phasor approach has been recently applied to
      fluorescence lifetime imaging microscopy, it has not been used extensively for
      cuvette studies. In the current study, we explore the applications of the method
      to in vitro samples. The phasors of binary and ternary mixtures of fluorescent
      dyes demonstrate the utility of the method for investigating complex mixtures.
      Data from excited state reactions, such as dipolar relaxation in membrane and
      protein systems and also energy transfer from the tryptophan residue to the
      chromophore in enhanced green fluorescent protein, are also presented.

PMID- 21078291
TI  - Mycotoxin detection on antibody-immobilized conducting polymer-supported
      electrochemically polymerized acacia gum.
AB  - Electrochemical polymerization of acacia gum (AG) was initiated by electroactive
      polyaniline (PANI) monomers by radical cation formation and their coupling
      reactions with AG molecules. R(CT) values obtained from electrochemical impedance
      spectroscopy analysis at various AG concentrations with PANI were drastically
      decreased, confirming formation of conducting AG complexes with PANI.
      Quantitative analysis of ochratoxin-A (OTA) detection in electrolyte was carried
      out on rabbit antibody-immobilized PANI and PANI-AG matrices. The observed
      sensitivities of 50, 150, and 250 mg AG-added PANI matrix-based platforms were
      3.3 +/- 0.5, 10.0 +/- 0.5, and 12.7 +/- 0.5 MUA/ng/ml, respectively. The
      sensitivity of only PANI electrodes was 2.6 +/- 0.3 MUA/ng/ml, which was
      relatively lower than AG-added PANI. This increase was due to the presence of
      glycan functional groups in AG molecules that supported the retention of activity
      of antibodies. In addition, enhanced electron transportation at AG-PANI film
      surface was observed due to formation of an electroactive polymer film of two
      different electroactive functions to contribute toward enhancement in the
      detection sensitivity.

PMID- 21078292
TI  - The biogenesis and physiological function of chloroplast superoxide dismutases.
AB  - Iron-superoxide dismutase (FeSOD) and copper/zinc-superoxide dismutase (Cu/ZnSOD)
      are evolutionarily conserved proteins in higher plant chloroplasts. These enzymes
      are responsible for the efficient removal of the superoxide formed during
      photosynthetic electron transport and function in reactive oxygen species
      metabolism. The availability of copper is a major determinant of Cu/ZnSOD and
      FeSOD expression. Analysis of the phenotypes of plants that over-express
      superoxide dismutases in chloroplasts has given support for the proposed roles of
      these enzymes in reactive oxygen species scavenging. However, over-production of
      chloroplast superoxide dismutase gives only limited protection to environmental
      stress and does not result in greatly improved whole plant performance.
      Surprisingly, plant lines that lack the most abundant Cu/ZnSOD or FeSOD
      activities perform as well as the wild-type under most conditions tested,
      indicating that these superoxide dismutases are not limiting to photoprotection
      or the prevention of oxidative damage. In contrast, a strong defect in
      chloroplast gene expression and development was seen in plants that lack the two
      minor FeSOD isoforms, which are expressed predominantly in seedlings and that
      associate closely with the chloroplast genome. These findings implicate reactive
      oxygen species metabolism in signaling and emphasize the critical role of sub
      cellular superoxide dismutase location. This article is part of a Special Issue
      entitled: Regulation of Electron Transport in Chloroplasts.

PMID- 21078293
TI  - Investigating the effects of L- to D-amino acid substitution and deamidation on
      the activity and membrane interactions of antimicrobial peptide anoplin.
AB  - Isolated from the venom sac of solitary spider wasp, Anoplius samariensis,
      anoplin is the smallest linear alpha-helical antimicrobial peptide found
      naturally with broad spectrum activity against both Gram-positive and Gram
      negative bacteria, and little hemolytic activity toward human erythrocytes.
      Deamidation was found to decrease the peptide's antibacterial properties. In the
      present work, interactions of amidated (Ano-NH2) and deamidated (Ano-OH) forms of
      anoplin as well as Ano-NH2 composed of all D-amino acids (D-Ano-NH2) with model
      cell membranes were investigated by means of Langmuir Blodgett (LB) technique,
      atomic force microscopy (AFM), X-ray photoemission electron microscopy (X-PEEM)
      and carboxyfluorescein leakage assay in order to gain a better understanding of
      the effect of these peptide modifications on membrane binding and lytic
      properties. According to LB, all three peptides form stable monolayers at the
      air/water interface with Ano-NH2 occupying a slightly greater area per molecule
      than Ano-OH. All three forms of the peptide interact preferentially with anionic
      1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DPPG), rather than
      zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer.
      Peptides form nanoscale clusters in zwitterionic but not in anionic monolayers.
      Finally, membrane lytic activity of all derivatives was found to depend strongly
      on membrane composition and lipid/peptide ratio. The results suggest that
      amidated forms of peptides are likely to possess higher membrane binding affinity
      due to the increased charge.

PMID- 21078294
TI  - Effects of concomitant use of fibroblast growth factor (FGF)-2 with beta
      tricalcium phosphate (beta-TCP) on the beagle dog 1-wall periodontal defect
      model.
AB  - The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta
      tricalcium phosphate (beta-TCP) on periodontal regeneration were investigated in
      the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were
      created in the mesial portion of both sides of the mandibular first molars, and
      0.3% FGF-2 plus beta-TCP or beta-TCP alone was administered. Radiographic
      evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with
      the defect site was removed and histologically analyzed. Radiographic findings
      showed that co-administration of FGF-2 significantly increased bone mineral
      contents of the defect sites compared with beta-TCP alone. Histologic analysis
      revealed that the length of the regenerated periodontal ligament, the cementum,
      distance to the junctional epithelium, new bone height, and area of newly formed
      bone were significantly increased in the FGF-2 group. No abnormal inflammatory
      response or ankylosis was observed in either group. These findings indicate the
      efficacy of concomitant use of FGF-2 and beta-TCP as an osteoconductive material
      for periodontal regeneration following severe destruction by progressive
      periodontitis.

PMID- 21078295
TI  - Chromosome translocation and its consequence in the genome of Burkholderia
      cenocepacia AU-1054.
AB  - Most bacterial genomes have one single chromosome. The species Burkholderia
      cenocepacia, a Gram-negative beta-proteobacterium, is one of the exceptions.
      Genomes of four strains of the species have been sequenced and each has three
      circular chromosomes. In the genus Burkholderia, there are another seven
      sequenced strains that have three chromosomes. In this paper, the numbers of
      essential genes and tRNA genes among the 11 strains of the genus Burkholderia are
      compared. Interestingly, it is found that the shortest chromosome of B.
      cenocepacia AU-1054 has much (over three times) more essential genes and tRNA
      genes than the corresponding chromosomes in the other 10 strains. However, no
      significant difference has been found on the two longer chromosomes among the 11
      strains. Non-homologous chromosomal translocation between chromosomes I and III
      in the species B. cenocepacia is found to be responsible for the unusual
      distribution of essential genes. The present work may contribute to the
      understanding of how the secondary chromosomes of multipartite bacterial genomes
      originate and evolve. The computer program, DEG_match, for comparatively
      identifying essential genes in any annotated bacterial genomes is freely
      available at http://cobi.uestc.edu.cn/resource/AU1054/.

PMID- 21078296
TI  - Accumulation of ceramide in the trachea and intestine of cystic fibrosis mice
      causes inflammation and cell death.
AB  - Cystic fibrosis is a hereditary metabolic disorder caused by mutations of the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene and characterized
      by severe intestinal and pulmonary symptoms, in particular intestinal
      obstruction, pancreatic insufficiency, chronic pulmonary inflammation, and
      microbial lung infections. Recent studies have demonstrated an accumulation of
      ceramide in the lungs of cystic fibrosis patients and in several mouse models.
      These findings showed that pulmonary ceramide concentrations play an important
      role in pulmonary inflammation and infection. In this study we investigated
      whether ceramide concentrations are also altered in the trachea and the intestine
      of cystic fibrosis mice and whether an accumulation of ceramide in these organs
      has functional consequences that are typical of cystic fibrosis. Our findings
      demonstrate a marked accumulation of ceramide in tracheal and intestinal
      epithelial cells of cystic fibrosis mice. When acid sphingomyelinase activity is
      inhibited by treating cystic fibrosis mice with amitriptyline or by genetic
      heterozygosity of acid sphingomyelinase in cystic fibrosis mice, ceramide
      concentrations in the trachea and the intestine are normalized. Moreover,
      increased rates of cell death and increased cytokine concentrations in the
      trachea, the intestine, or both were normalized by the inhibition of acid
      sphingomyelinase activity and the concomitant normalization of ceramide
      concentrations. These findings suggest that ceramide plays a crucial role in
      inflammation and increased rates of cell death in several organs of cystic
      fibrosis mice.

PMID- 21078297
TI  - Differential expression of cellular microRNAs in HPV-11 transfected cells. An
      analysis by three different array platforms and qRT-PCR.
AB  - Human papillomavirus type 11 (HPV-11) infects the genital and the respiratory
      tract leading to condylomas and respiratory papillomatosis. HPV infections are
      restricted to epithelial tissue and the progression through the virus lifecycle
      is tightly coordinated to the differentiation of the host cell. The changes of
      cellular microRNAs by HPV-11 gene expression were investigated in a cell culture
      model of HaCaT cells transfected with HPV-11, with the goal of understanding
      which cellular processes were affected by the virus. Human microRNA profiling was
      conducted on three different array platform systems and because very few
      microRNAs (miR-663, -638, -149* and -92b*) were consistently found in all three
      array data sets we performed extensive statistical analyses of the array data and
      the qRT-PCR validation. We assume that the most reliable differentially expressed
      microRNAs are the ones identified by more than one array platform. We also show
      that TaqMan(r) qRT-PCR validation is of limited use for less abundant microRNAs.

PMID- 21078298
TI  - Nano-mechanical properties of living cells expressing constitutively active RhoA
      effectors.
AB  - Filamentous actin and myosin-II are major determinants of cell mechanics and are
      tightly regulated by a small guanosine triphosphatase, RhoA, and its downstream
      effectors. We examined the effects of constitutively active mutants of RhoA
      effectors, which have not been reported before, on cortical stiffness of living
      cells by using scanning probe microscopy, fluorescence microscopy, and truncated
      mutants of RhoA effectors labeled with a fluorescent protein. Our data indicated
      that expression of a constitutively active mutant of Dia1, a formin-family actin
      polymerizer, enhanced cortical stiffness and increased actin filament quantity in
      cells. Furthermore, expression of a constitutively active mutant of Rho
      associated coiled-coil kinase, a myosin-II activator, softened the cell cortex
      but increased myosin-II activity. Our findings provide new insights into
      anomalous mechanics of cells, which is a topic of current interest in a variety
      of biological research fields.

PMID- 21078299
TI  - Role of resveratrol in FOXO1-mediated gluconeogenic gene expression in the liver.
AB  - During a state of fasting, the blood glucose level is maintained by hepatic
      gluconeogenesis. SIRT1 is an important metabolic regulator during nutrient
      deprivation and the liver-specific knockdown of SIRT1 resulted in decreased
      glucose production. We hypothesize that SIRT1 is responsible for the upregulation
      of insulin-suppressed gluconeogenic genes through the deacetylation of FOXO1.
      Treatment of primary cultured hepatocytes with resveratrol increased insulin
      repressed PEPCK and G6Pase mRNA levels, which depend on SIRT1 activity. We found
      that the resveratrol treatment resulted in a decrease in the phosphorylation of
      Akt and FOXO1, which are independent of SIRT1 action. Fluorescence microscopy
      revealed that resveratrol caused the nuclear localization of FOXO1. In the
      nucleus, FOXO1 is deacetylated by SIRT1, which might make it more accessible to
      the IRE of the PEPCK and G6Pase promoter, causing an increase in their gene
      expression. Our results indicate that resveratrol upregulates the expression of
      gluconeogenic genes by attenuating insulin signaling and by deacetylating FOXO1,
      which are SIRT1-independent in the cytosol and SIRT1-dependent in the nucleus,
      respectively.

PMID- 21078300
TI  - PIH1D1, a subunit of R2TP complex, inhibits doxorubicin-induced apoptosis.
AB  - We have previously reported that the two components of R2TP complex, RNA
      polymerase II-associated protein 3 (RPAP3), and Reptin, regulate apoptosis. Here
      we characterize another component of the complex, PIH1 domain containing protein
      1 (PIH1D1). PIH1D1 interacts with both RPAP3 and Monad in HEK293 or U2OS cells.
      PIH1D1 transcripts were abundant in lung, leukocyte, and placenta. The reduction
      in endogenous PIH1D1 by siRNA enhanced apoptosis and caspase-3 activation induced
      by doxorubicin in U2OS cells. These results suggest that PIH1D1 may also function
      as a novel modulator of apoptosis pathway.

PMID- 21078301
TI  - Universal antibodies against the highly conserved influenza fusion peptide cross
      neutralize several subtypes of influenza A virus.
AB  - The fusion peptide of influenza viral hemagglutinin plays a critical role in
      virus entry by facilitating membrane fusion between the virus and target cells.
      As the fusion peptide is the only universally conserved epitope in all influenza
      A and B viruses, it could be an attractive target for vaccine-induced immune
      responses. We previously reported that antibodies targeting the first 14 amino
      acids of the N-terminus of the fusion peptide could bind to virtually all
      influenza virus strains and quantify hemagglutinins in vaccines produced in
      embryonated eggs. Here we demonstrate that these universal antibodies bind to the
      viral hemagglutinins in native conformation presented in infected mammalian cell
      cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant
      fusion of viral and cellular membranes. These results suggest that this unique,
      highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently
      to be attacked by the antibodies during the course of infection and merits
      further investigation because of potential importance in the protection against
      diverse strains of influenza viruses.

PMID- 21078302
TI  - Glutaredoxin-1 regulates TRAF6 activation and the IL-1 receptor/TLR4 signalling.
AB  - Glutaredoxin-1 (GRX-1) is a cytoplasmic enzyme that highly contributes to the
      antioxidant defense system. It catalyzes the reversible reduction of glutathione
      protein mixed disulfides, a process called deglutathionylation. Here, we
      investigated the role of GRX-1 in the pathway triggered by interleukin-1/Toll
      like receptor 4 (IL-1R/TLR4) by using RNA interference (RNAi) in HEK293 and HeLa
      cells. TNF receptor-associated factor 6 (TRAF6) is an intermediate signalling
      molecule involved in the signal transduction by members of the interleukin-1/Toll
      like receptor (IL-1R/TLR) family. TRAF6 has an E3 ubiquitin ligase activity which
      depends on the integrity of an amino-terminal really interesting new gene (RING)
      finger motif. Upon receptor activation, TRAF6 undergoes K63-linked auto
      polyubiquitination which mediates protein-protein interactions and signal
      propagation. Our data showed that IL-1R and TLR4-mediated NF-kappaB induction was
      severely reduced in GRX-1 knockdown cells. We found that the RING-finger motif of
      TRAF6 is S-glutathionylated under normal conditions. Moreover, upon IL-1
      stimulation TRAF6 undergoes deglutathionylation catalyzed by GRX-1. The
      deglutathionylation of TRAF6 is essential for its auto-polyubiquitination and
      subsequent activation. Taken together, our findings reveal another signalling
      molecule affected by S-glutathionylation and uncover a crucial role for GRX-1 in
      the TRAF6-dependent activation of NF-kappaB by IL-1R/TLRs.

PMID- 21078303
TI  - Perimenopausal use of hormone therapy is associated with enhanced memory and
      hippocampal function later in life.
AB  - Evidence suggests that initiation of some forms of hormone therapy (HT) early in
      the perimenopausal or postmenopausal stage might confer benefit to verbal memory
      and the neural systems underlying memory, whereas late-life initiation confers no
      benefit or harm. This "critical window hypothesis" remains a topic of debate.
      Using functional magnetic resonance imaging (fMRI), we examined the long-term
      impact of perimenopausal HT use on brain function during performance of verbal
      and figural memory tasks. Participants were 34 postmenopausal women (mean age 60
      years) from the Melbourne Women's Midlife Health Project and included 17 early
      (perimenopausal) and continuous users of HT and 17 never users matched on age,
      education, and verbal knowledge. Continuous HT use from the perimenopausal stage
      versus no use was validated with prospective daily diary records and study visit
      data. The primary outcome was patterns of brain activation in an a priori region
      of interest in the medial temporal lobe during verbal encoding and recognition of
      words. Results indicated that perimenopausal HT users performed better than
      nonusers on the imaging verbal memory task (p<.05). During verbal recognition,
      perimenopausal HT users showed increased activation in the left hippocampus and
      decreased activation in the parahippocampal gyrus bilaterally compared with never
      users. Each of these patterns of activation was associated with better memory
      performance on the imaging memory task. These results suggest that perimenopausal
      use of HT might confer long-term benefits to verbal memory and the brain systems
      underlying verbal memory. More generally, the results support the critical window
      hypothesis.

PMID- 21078305
TI  - Is schizophrenia on the autism spectrum?
AB  - With the ongoing consideration of the diagnostic criteria for mental disorders
      that is active in the Diagnostic and Statistical Manual of Mental Disorders (DSM
      V) and International Classification of Diseases (ICD-11) revision processes, it
      is timely to review the phenomenological overlap between autism and
      schizophrenia. These disorders have at various times been regarded alternatively
      as closely related and as non-overlapping and incompatible. Nevertheless, there
      are several reports in the literature that have described individuals with both
      autism and schizophrenia, and the broader phenotypes of these disorders clearly
      intersect. Recent studies reveal theory of mind deficits in both disorders, and
      mirror neuron impairments also appear to be shared. There also may be similar
      connectivity deficits emerging in functional imaging studies, and both disorders
      share several genetic signals that are being identified through detection of copy
      number variants. Taken together, these data suggest that it may be time to
      revisit the possibility that these disorders are related.

PMID- 21078304
TI  - Pharmacological reversal of synaptic plasticity deficits in the mouse model of
      fragile X syndrome by group II mGluR antagonist or lithium treatment.
AB  - Fragile X syndrome is the leading single gene cause of intellectual disabilities.
      Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate
      receptor (mGluR) antagonists or lithium rescues social and cognitive impairments.
      A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long
      term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the
      hippocampus. Here we examine the effects of chronic treatment of Fragile X mice
      in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses.
      We find that long-term lithium treatment initiated during development (5-6 weeks
      of age) and continued throughout the lifetime of the Fragile X mice until 9-11
      months of age restores normal mGluR-LTD. Additionally, chronic short-term
      treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium
      or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the
      findings of successful pharmacologic intervention from the Drosophila model into
      the mouse model of Fragile X syndrome is an important advance, in that this
      identifies and validates these targets as potential therapeutic interventions for
      the treatment of individuals afflicted with Fragile X syndrome.

PMID- 21078306
TI  - Circadian modulation of interval timing in mice.
AB  - Temporal perception is fundamental to environmental adaptation in humans and
      other animals. To deal with timing and time perception, organisms have developed
      multiple systems that are active over a broad range of order of magnitude, the
      most important being circadian timing, interval timing and millisecond timing.
      The circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the
      hypothalamus, and is driven by a self-sustaining oscillator with a period close
      to 24h. Time estimation in the second-to-minutes range--known as interval timing-
      involves the interaction of the basal ganglia and the prefrontal cortex. In this
      work we tested the hypothesis that interval timing in mice is sensitive to
      circadian modulations. Animals were trained following the peak-interval (PI)
      procedure. Results show significant differences in the estimation of 24-second
      intervals at different times of day, with a higher accuracy in the group trained
      at night, which were maintained under constant dark (DD) conditions. Interval
      timing was also studied in animals under constant light (LL) conditions, which
      abolish circadian rhythmicity. Mice under LL conditions were unable to acquire
      temporal control in the peak interval procedure. Moreover, short time estimation
      in animals subjected to circadian desynchronizations (modeling jet lag-like
      situations) was also affected. Taken together, our results indicate that short
      time estimation is modulated by the circadian clock.

PMID- 21078307
TI  - Immunoneutralization of melanin-concentrating hormone (MCH) in the dorsal raphe
      nucleus: effects on sleep and wakefulness.
AB  - Hypothalamic neurons that utilize melanin-concentrating hormone (MCH) as a
      neuromodulator exert a positive control over energy homeostasis, inducing feeding
      and decreasing metabolism. Recent studies have shown also that this system plays
      a role in the generation and/or maintenance of sleep. MCHergic neurons project to
      the serotonergic dorsal raphe nucleus (DR), a neuroanatomical structure involved
      in several functions during wakefulness (W), and in the regulation of rapid-eye
      movements (REM) sleep. Recently, we determined the effect of MCH microinjected
      into the DR on sleep variables in the rat. MCH produced a marked increment of REM
      sleep, whereas slow wave sleep (SWS) showed only a moderate increase. In the
      present study, we analyze the effect of immunoneutralization of MCH in the DR on
      sleep and W in the rat. Compared to the control solution, microinjections of anti
      MCH antibodies (1/100 solution in 0.2 MUl) induced a significant increase in REM
      sleep latency (31.2+/-7.1 vs. 84.2+/-24.8 min, p<0.05) and a decrease of REM
      sleep time (37.8+/-5.4 vs. 17.8+/-2.9 min, p<0.05) that was related to the
      reduction in the number of REM sleep episodes. In addition, there was an increase
      of total W time (49.8+/-4.6 vs. 72.0+/-5.7 min, p<0.01). Light sleep and SWS
      remained unchanged. The intra-DR administration of a more diluted solution of
      anti-MCH antibodies (1/500) or rabbit pre-immune serum did not modify neither W
      nor REM sleep variables. Our findings strongly suggest that MCH released in the
      DR facilitates the occurrence of REM sleep.

PMID- 21078308
TI  - Do common variants play a role in risk for autism? Evidence and theoretical
      musings.
AB  - Both rare and common genetic variants underlie risk for almost any complex
      disease. Over the past few years a common tool for identifying common risk
      variants is genome-wide association or GWA. Our analyses focus on results from
      GWA targeting common variants affecting risk for autism spectrum disorders (ASD).
      Thus far three large GWA studies have been published, each of which highlights a
      single, non-overlapping risk locus. Evaluation of these studies suggests that
      combination of their data would diminish evidence for all of these loci, making
      none of them significant. Despite this paucity of findings, statistical theory
      can be used to infer a plausible distribution of effect sizes for SNPs affecting
      risk for ASD. We lay out this theory, calculate plausible distributions, and
      discuss the results in the context of results from GWA studies for schizophrenia.

PMID- 21078309
TI  - Feature priming and the capture of visual attention: linking two ambiguity
      resolution hypotheses.
AB  - Visual search for a unique stimulus is often faster when the feature defining
      this target is repeated. Recent research has related this feature priming to
      ambiguity: priming effects appear stronger when the search target is perceptually
      ambiguous, as when the search array contains a salient distractor. Here we link
      the ambiguity that underlies feature priming to ambiguity in neural
      representation caused by the receptive field organization of visual cortex. We
      show that as the magnitude of neural activity involved in resolving perceptual
      ambiguity in early stages of visual cortex increases-indexed in posterior aspects
      of the N2pc component of the visual-event related potential--so does the
      behavioral feature priming effect. When ambiguity resolution mechanisms act
      strongly and the target repeats, target processing is facilitated. When these
      mechanisms act strongly, but the features that have previously defined the target
      come to characterize the distractor, attention is captured to the distractor
      location. These results suggest that ambiguity and the attentional mechanisms
      responsible for resolving it play central roles in feature priming.

PMID- 21078310
TI  - Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic
      acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic
      rats.
AB  - Diabetes mellitus causes derangement of carbohydrate, protein and lipid
      metabolism which eventually leads to a number of secondary complications.
      Terminalia bellerica is widely used in Indian medicine to treat various diseases
      including diabetes. The present study was carried out to isolate and identify the
      putative antidiabetic compound from the fruit rind of T. bellerica and assess its
      chemico-biological interaction in experimental diabetic rat models. Bioassay
      guided fractionation was followed to isolate the active compound, structure was
      elucidated using (1)H and (13)C NMR, IR, UV and mass spectrometry and the
      compound was identified as gallic acid (GA). GA isolated from T. bellerica and
      synthetic GA was administered to streptozotocin (STZ)-induced diabetic male
      Wistar rats at different doses for 28 days. Plasma glucose level was
      significantly (p<0.05) reduced in a dose-dependent manner when compared to the
      control.Histopathological examination of the pancreatic sections showed
      regeneration of beta-cells of islets of GA-treated rats when compared to
      untreated diabetic rats. In addition, oral administration of GA (20mg/kg bw)
      significantly decreased serum total cholesterol, triglyceride, LDL-cholesterol,
      urea, uric acid, creatinine and at the same time markedly increased plasma
      insulin, C-peptide and glucose tolerance level. Also GA restored the total
      protein, albumin and body weight of diabetic rats to near normal. Thus our
      findings indicate that gallic acid present in fruit rind of T. bellerica is the
      active principle responsible for the regeneration of beta-cells and normalizing
      all the biochemical parameters related to the patho-biochemistry of diabetes
      mellitus and hence it could be used as a potent antidiabetic agent.

PMID- 21078311
TI  - Improved measurement of LINE-1 sequence methylation for cancer detection.
AB  - BACKGROUND: Methylation of long interspersed nuclear element-1 (LINE-1) sequences
      varies among normal cells and it is often decreased in cancer genomes and white
      blood cells (WBC) of cancer patients. Current measurement techniques of genome
      wide level are inadequate because LINE-1 methylation is distinctive at each
      locus. Here, we improved the detection of cancer by combining information of LINE
      1 methylation pattern and level. METHODS: Combined bisulfite restriction analysis
      (COBRA) of LINE-1, COBRA LINE-1, was used to test cancer cell lines, two oral
      rinse cohorts, and WBC from normal and cancer patients. COBRA LINE-1 separated
      LINE-1 sequences into 4 products depending on the methylation statuses of 2 CpG
      dinucleotides, as follows: 2 unmethylated CpGs ((u)C(u)C), partial methylation
      ((m)C(u)C), 1 methylated CpG ((m)C), and 1 unmethylated CpG ((u)C). RESULTS: The
      association between (m)C(u)C and (u)C(u)C was directly correlated in normal cells
      (r=0.4895, p=0.0009) but inversely correlated in cancer (r=-0.8979, p=0.0002).
      Oral rinse AUC values of (u)C(u)C were 0.763 and 0.926 and methylation levels
      were 0.707 and 0.621, respectively. (u)C(u)C, but not overall methylation level,
      differentiated cancer WBC from normal (p=0.0082 and p=0.4830, respectively).
      CONCLUSION: LINE-1 partial methylation represents hypomethylation in normal cells
      but hypermethylation in cancer cells. This information improves LINE-1
      methylation detection in cancer.

PMID- 21078312
TI  - High-throughput plasma docetaxel quantification by liquid chromatography-tandem
      mass spectrometry.
AB  - BACKGROUND: The most valuable treatment option for breast, prostate and lung
      carcinomas is at present represented by a low dose of docetaxel, administered on
      a weekly basis. A better understanding of docetaxel pharmacokinetic and
      pharmacodynamic profiles could lead to an improvement in this dose regimen
      efficacy. METHODS: In this study a high-throughput method is described for the
      rapid quantification of docetaxel for large clinical pharmacology investigations.
      This analytical approach is based on an automatic on-line purification and
      enrichment technique followed by a measurement in tandem mass spectrometry
      through Multiple Reaction Monitoring. RESULTS: The assay was validated over a
      0.15-1500 ng/mL range. Intra-day precision ranged from 1.9% to 6.4%, while the
      inter-day was between 7.6% and 11.2%. The mean deviation from the nominal value
      ranged from -0.5% to 5.6% for the intra-day, and from -0.4% to 3.1% for the inter
      day assay. Clinical applicability was demonstrated by measuring plasma
      pharmacokinetics in patients receiving weekly 25-35 mg/m(2) of docetaxel.
      CONCLUSION: The proposed LC-MS/MS assay was found to have a better performance
      than previously reported methods in terms of sensitivity and sample preparation.
      It does not require any laborious pre-analytical manipulation and can be easily
      employed in large clinical pharmacology studies.

PMID- 21078313
TI  - Reduction of unsuitable specimens: a more radical and comprehensive approach is
      needed.

PMID- 21078314
TI  - Identification of differentially expressed proteins in the aqueous humor of
      primary congenital glaucoma.
AB  - Primary Congenital Glaucoma (PCG) is an autosomal recessive disease caused by an
      abnormal development of the anterior chamber angle. Although, PCG has been linked
      to several genetic loci, the role that the genes at these loci or their encoded
      proteins play in the pathophysiology of PCG and development of the anterior
      chamber is not known. To identify proteins that may be altered in PCG and that
      may help in understanding the underlying pathophysiology of the disease, we took
      a global proteomics approach. Tryptic digests of the complex mixtures of proteins
      in aqueous humor were analyzed using Liquid Chromatography/Mass Spectrometry (LC
      MS/MS). Proteins were identified by searching the data against the human subset
      of the UniProt database. The proteomes of aqueous humor in PCG (n = 7) and
      patients undergoing cataract surgery as control (n = 4) were compared based on
      the scan counts of comparable proteins. Using stringent filtering criteria,
      Apolipoprotein A-IV (APOA-IV), Albumin and Antithrombin 3 (ANT3) were detected at
      significantly higher levels in PCG AH compared to control, whereas Transthyretin
      (TTR), Prostaglandin-H2 D-isomerase (PTGDS), Opticin (OPT) and Interphotoreceptor
      Retinoid Binding Protein (IRBP) were detected at significantly lower levels. Many
      of these proteins play a role in retinoic acid (RA) binding/transport and have
      been implicated in the pathogenesis of neurodegenerative diseases such as
      Alzheimer's (AD). It is possible that similar to AD, the pathologic changes in
      PCG during development could be influenced by the availability of RA in the
      anterior chamber.

PMID- 21078318
TI  - Light-scattering technologies for field carcinogenesis detection: a modality for
      endoscopic prescreening.

PMID- 21078321
TI  - The hypophysial pars tuberalis transduces photoperiodic signals via multiple
      pathways and messenger molecules.
AB  - Located between the median eminence, the portal vessels, and the pars distalis
      (PD) of the hypophysis, the hypophysial pars tuberalis (PT) is an important
      center for transmission of photoperiodic information to neuroendocrine circuits
      involved in the control of reproduction, metabolism and behavior. Despite
      enormous and long lasting efforts, output pathways and messenger molecules from
      the PT have been unraveled only recently. Most interestingly, the PT sends its
      signals in two directions: via a "retrograde" pathway to the hypothalamus and via
      an "anterograde" pathway to the PD. TSH has been identified as a messenger of the
      "retrograde" pathway. As discovered in Japanese quail, TSH triggers molecular
      cascades mediating thyroid hormone conversion in the mediobasal hypothalamus
      (MBH) to activate the gonadal axis. These molecular mechanisms are conserved in
      photoperiodic mammals, and even in non-photoperiodic laboratory mice. The search
      for molecules of the "anterograde" pathway was for a long time focused on PT
      specific neuropeptides, the so-called "tuberalins". The discovery of a PT
      intrinsic endocannabinoid system in hamsters which is regulated by the
      photoperiod provides strong experimental evidence that the PT also synthesizes
      lipidergic messengers. To date, 2-arachidonoylglycerol (2-AG) appears as the most
      important lipidergic messenger from the PT. The primary target of 2-AG, the
      cannabinoid receptor 1 (CB1) is expressed in the hamster PD. A PT-intrinsic
      endocannabinoid system also exists in man and CB1 receptors are demonstrated in
      ACTH-producing cells and folliculo-stellate cells of the human PD. These data
      lend support to the hypothesis that endocannabinoids function as messengers of
      the anterograde pathway.

PMID- 21078320
TI  - Kruppel-like factor 5 protects against dextran sulfate sodium-induced colonic
      injury in mice by promoting epithelial repair.
AB  - BACKGROUND & AIMS: Kruppel-like factor 5 (KLF5) is a transcription factor that
      promotes proliferation, is highly expressed in dividing crypt cells of the
      gastrointestinal epithelium, and is induced by various stress stimuli. We sought
      to determine the role of KLF5 in colonic inflammation and recovery by studying
      mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Wild-type (WT)
      and Klf5(+/-) mice were given DSS in the drinking water to induce colitis. For
      recovery experiments, mice were given normal drinking water for 5 days after DSS
      administration. The extent of colitis was determined using established clinical
      and histological scoring systems. Immunohistochemical and immunoblotting analyses
      were used to examine proliferation, migration, and expression of the epidermal
      growth factor receptor. RESULTS: Klf5 expression was increased in colonic tissues
      of WT mice given DSS; induction of Klf5 was downstream of mitogen-activated
      protein kinase signaling. In DSS-induced colitis, Klf5(+/-) mice exhibited
      greater sensitivity to DSS than WT mice, with significantly higher clinical and
      histological colitis scores. In recovery experiments, Klf5(+/-) mice showed poor
      recovery, with continued weight loss and higher mortality than WT mice. Klf5(+/-)
      mice from the recovery period had reduced epithelial proliferation and cell
      migration at sites of ulceration compared to WT mice; these reductions correlated
      with reduced expression of epidermal growth factor receptor. CONCLUSIONS:
      Epithelial repair is an important aspect of recovery from DSS-induced colitis.
      The transcription factor KLF5 regulates mucosal healing through its effects on
      epithelial proliferation and migration.

PMID- 21078322
TI  - Individual variation in plasma testosterone levels and its relation to badge size
      in House Sparrows Passer domesticus: it's a night-and-day difference.
AB  - The steroid hormone testosterone (T) plays a central role in the regulation of
      reproduction in animals. Although seasonal variation in T levels is well-studied,
      differences between day and night have only been described in relatively few
      species, and daily within-individual variation has been largely neglected when
      evaluating the relationship between T and the expression of sexual ornaments or
      behavior. We measured plasma T levels during day and night in a captive
      population of House Sparrows, and analyzed their relationship with an important
      male ornament--badge size. T levels were on average twice as high at night than
      during daytime. This was true in all seasons, and in both males and females.
      Disturbance of the birds at night, but not during the day, led to significantly
      lower T levels, suggesting a rapid drop after an individual wakes up. The
      relationship between T levels and badge size depended on the time when T was
      measured. During the breeding season, badge size was strongly positively
      correlated with night-time, but not with daytime T levels. This suggests that
      badge size signals information related to an individual's maximum potential T
      level such as social dominance. Our study highlights that integrative research on
      the endocrine control of ornament expression needs to take diel variation in
      hormone levels into account.

PMID- 21078323
TI  - Multiple cocaine- and amphetamine-regulated transcript (CART) genes in medaka,
      Oryzias latipes: cloning, tissue distribution and effect of starvation.
AB  - The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is
      important in the regulation of food intake in mammals and fish. The tissue
      distributions of six CART cDNAs (cart ch3, ch4, ch6, ch9, ch11, and ch22) from
      medaka, Oryzias latipes, were cloned and the effect of starvation on their
      expression was examined. As in other species, medaka cart ch3, ch4, ch6, ch9, and
      ch22 consisted of three exons, while medaka cart ch11 contained four. The six
      cysteine residues at the C-terminal end of the CART motif and three-dimensional
      structure were well conserved in all medaka CART peptides. Tissue distribution
      analysis revealed that cart ch3, ch4, ch6, ch11, and ch22 were primarily
      expressed in the brain, but that the highest rates of cart ch9 expression
      occurred in the skin, suggesting different functions among the homologous genes.
      Although CART ch3 mRNA levels decreased in response to 17 days starvation, these
      levels were restored by re-feeding. However, the finding that the five other CART
      mRNAs did not respond to starvation suggests that only CART ch3 has an
      anorexigenic function in medaka.

PMID- 21078324
TI  - Context-specific territorial behavior in urban birds: no evidence for involvement
      of testosterone or corticosterone.
AB  - Testosterone produced by the gonads is a primary mediator of seasonal patterns of
      territoriality and may directly facilitate territorial behavior during an
      encounter with a potential intruder. Costs and benefits associated with
      territoriality can vary as a function of habitat, for example through differences
      in resource distribution between areas occupied by different individuals. We
      investigated behaviors in response to simulated territorial intrusions (hereafter
      territorial behaviors) in urban (Phoenix, Arizona) and nearby desert populations
      of two Sonoran Desert birds (Curve-billed Thrasher and Abert's Towhee). We also
      examined the degree to which these behaviors are mediated by testosterone (T) and
      the adrenal steroid, corticosterone (CORT), which can interact with T in
      territorial contexts. In both species, urban birds displayed more territorial
      behaviors than their desert conspecifics, but this difference was not associated
      with variation in either plasma total or in plasma free (i.e., unbound to binding
      globulins) T or CORT. In addition, neither plasma T nor plasma CORT changed as a
      function of duration of the simulated territorial intrusion. Urban Abert's
      Towhees displayed more territorial behaviors in areas where their population
      densities were high than in areas of low population densities. Urban Curve-billed
      Thrashers displayed more territorial behaviors in areas with a high proportion of
      desert-type vegetation, particularly in areas that differed in vegetation
      composition from nearby randomly sampled areas, than in areas with a high
      proportion of exotic or non-desert type vegetation. Associations between
      territorial behavior and habitat characteristics were not related to plasma T or
      CORT. Understanding the hormonal processes underlying these associations between
      behavior and habitat may provide insight into how free-ranging animals assess
      territorial quality and alter their defensive behavior accordingly.

PMID- 21078325
TI  - MALDI immunoscreening (MiSCREEN): a method for selection of anti-peptide
      monoclonal antibodies for use in immunoproteomics.
AB  - A scalable method for screening and selection of peptide-specific monoclonal
      antibodies (mAbs) is described. To identify high affinity anti-peptide mAbs in
      hybridoma supernatants, antibodies were captured by magnetic affinity beads
      followed by binding of specific peptides from solution. After timed washing
      steps, the remaining bound peptides were eluted from the beads and detected by
      matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS). This allowed measurement of monovalent interactions of
      peptides with single antigen binding sites on the antibodies, thus reflecting
      antibody affinity rather than avidity. Antibodies that were able to bind target
      peptides from solution phase and retain them during washing for a minimum of 10
      min were identified by the strength of the appropriate m/z peptide MS signals
      obtained. This wash time reflects the minimum peptide dissociation time required
      for use of these antibodies in several current immuno-mass spectrometry assays.
      Kinetic analysis of antibody-peptide binding by surface plasmon resonance (SPR)
      showed that the selected antibodies were of high affinity and, most importantly,
      had low dissociation constants. This method, called MALDI immunoscreening
      (MiSCREEN), thus enables rapid screening and selection of high affinity anti
      peptide antibodies that are useful for a variety of immunoproteomics
      applications. To demonstrate their functional utility in immuno-mass spectrometry
      assays, we used the selected, purified RabMAbs to enrich natural (tryptic)
      peptides from digested human plasma.

PMID- 21078326
TI  - Changes in oxygen and carbon dioxide environment alter gene expression of cowpea
      bruchids.
AB  - Hermetic storage is a widely adopted technique for preventing stored grain from
      being damaged by storage insect pests. In the air-tight container, insects
      consume oxygen through metabolism while concomitantly raising carbon dioxide
      concentrations through respiration. Previous studies on the impact of hypoxia and
      hypercapnia on feeding behavior of cowpea bruchids have shown that feeding
      activity gradually decreases in proportion to the changing gas concentrations and
      virtually ceases at approximately 3-6% (v/v) oxygen and 15-18% carbon dioxide.
      Further, a number of bruchid larvae are able to recover their feeding activity
      after days of low oxygen and high carbon dioxide, although extended exposure
      tends to reduce survival. In the current study, to gain insight into the
      molecular mechanism underpinning the hypoxia-coping response, we profiled
      transcriptomic responses to hypoxia/hypercapnia (3% oxygen, 17% carbon dioxide
      for 4 and 24h) using cDNA microarrays, followed by quantitative RT-PCR
      verification of selected gene expression changes. A total of 1046 hypoxia
      responsive cDNAs were sequenced; these clustered into 765 contigs, of which 645
      were singletons. Many (392) did not show homology with known genes, or had
      homology only with genes of unknown function in a BLAST search. The identified
      differentially-regulated sequences encoded proteins presumptively involved in
      nutrient transport and metabolism, cellular signaling and structure, development,
      and stress responses. Gene expression profiles suggested that insects compensate
      for lack of oxygen by coordinately reducing energy demand, shifting to anaerobic
      metabolism, and strengthening cellular structure and muscular contraction.

PMID- 21078328
TI  - Orientation mechanisms and sensory organs involved in host location in a dipteran
      parasitoid larva.
AB  - The robber fly Mallophora ruficauda is one of the principal pests of apiculture
      in the Pampas region of Argentina. Larvae are solitary ectoparasitoids of third
      instar scarab beetle larvae. Females of M. ruficauda do not lay eggs on or near
      the hosts, but on tall grasses. After hatching, larvae are dispersed by the wind
      and drop to the ground, where they dig and search for potential hosts. It is
      known that second-instar larvae of M. ruficauda exhibit active host-searching
      behaviour towards their preferred hosts, i.e., third-instar larvae of
      Cyclocephala signaticollis. Although host-location seems to be mediated by
      chemical cues, the mechanism of orientation and the sensory organs involved in
      host location remain unknown. We carried out behavioural experiments in the
      laboratory to address these questions. We also tested whether the orientation
      behaviour is exclusively based on the use of chemical cues. We found that larvae
      of M. ruficauda detect the chemicals with chemosensilla on the maxillary palps.
      Only one maxillary palp suffices for orientation, but their bilateral ablation
      abolishes orientation. Besides, an hexane extract of the host body was as
      attractive as a live host. Our results support that M. ruficauda larvae find
      their hosts underground by means of chemoklinotaxis.

PMID- 21078329
TI  - The behaviour of a neutral model of weight regulated only by body mass.
AB  - While there are many mechanisms that may be involved in the regulation of body
      mass in humans and other animals, it is not so clear how much regulation is
      needed beyond the negative feedback effect of body mass itself. Here we model
      weight changes as a stochastic process, and show that it behaves approximately as
      an autoregressive process. Using published estimates of the energy cost of weight
      gain, the effect of weight on resting metabolic rate and the daily variation in
      intake and activity, we show that fluctuations in weight will be small. The
      effect of excess intake is also examined, and the assumptions and limitations of
      the model are discussed.

PMID- 21078327
TI  - RNA interference in Lepidoptera: an overview of successful and unsuccessful
      studies and implications for experimental design.
AB  - Gene silencing through RNA interference (RNAi) has revolutionized the study of
      gene function, particularly in non-model insects. However, in Lepidoptera (moths
      and butterflies) RNAi has many times proven to be difficult to achieve. Most of
      the negative results have been anecdotal and the positive experiments have not
      been collected in such a way that they are possible to analyze. In this review,
      we have collected detailed data from more than 150 experiments including all to
      date published and many unpublished experiments. Despite a large variation in the
      data, trends that are found are that RNAi is particularly successful in the
      family Saturniidae and in genes involved in immunity. On the contrary, gene
      expression in epidermal tissues seems to be most difficult to silence. In
      addition, gene silencing by feeding dsRNA requires high concentrations for
      success. Possible causes for the variability of success in RNAi experiments in
      Lepidoptera are discussed. The review also points to a need to further
      investigate the mechanism of RNAi in lepidopteran insects and its possible
      connection to the innate immune response. Our general understanding of RNAi in
      Lepidoptera will be further aided in the future as our public database at
      http://insectacentral.org/RNAi will continue to gather information on RNAi
      experiments.

PMID- 21078331
TI  - Mathematical modeling of bacterial virulence and host-pathogen interactions in
      the Dictyostelium/Pseudomonas system.
AB  - We present some studies on the mechanisms of pathogenesis based on experimental
      work and on its interpretation through a mathematical model. Using a collection
      of clinical strains of the opportunistic human pathogen Pseudomonas aeruginosa,
      we performed co-culture experiments with Dictyostelium amoebae, to investigate
      the two organisms' interaction, characterized by a cross action between amoeba,
      feeding on bacteria, and bacteria exerting their pathogenic action against
      amoeba. In order to classify bacteria virulence, independently of this cross
      interaction, we have also performed killing experiments of bacteria against the
      nematode Caenorhabditis elegans. A mathematical model was developed to infer how
      the populations of the amoeba-bacteria system evolve according to a number of
      parameters, taking into account the specific features underlying the interaction.
      The model does not fall within the class of traditional prey-predator models
      because not only does an amoeba feed on bacteria, but also it is in turn attacked
      by them; thus the model must include a feedback term modeling this further
      interaction aspect. The model shows the existence of multiple steady states and
      the resulting behavior of the solutions, showing bi-stability of the system,
      gives a qualitative explanation of the co-culture experiments.

PMID- 21078332
TI  - Age distribution of trees in stationary forest system.
AB  - A statistical theory for the age distribution of spatially dominant trees in a
      stationary forest system is developed. The result depends whether or not
      mortality is spatially correlated, as well as whether or not the stand boundaries
      are pre-determined. In the case of spatially non-correlated mortality, the tree
      age distribution is an exponential with survival rate as the base. In the case of
      spatially correlated mortality within a stand with pre-determined boundaries, the
      age distribution within the stand is an exponential with natural base. For a
      small stand, the median life span of the stand is inversely proportional to the
      number of trees (n); the median life span in relation to stand closure time is
      inversely proportional to nln(n). For a large stand, the stand life does not
      extend to the closure time. The behaviour of a forest system without fixed stand
      boundaries depends on the dimensionality of the system. In the case of a one
      dimensional system, the longevity distribution is exponential, most of the trees
      however having the same longevity. Consequently, the probability density of tree
      age is constant. However, the probability mass of size of catastrophe destroying
      a particular tree is evenly distributed. This is due to trees being rapidly born
      on empty areas in the beginning of the life cycle, and clusters rapidly growing
      into larger ones close to the end of tree life.

PMID- 21078333
TI  - Dynamic calibration of our sense of time.
AB  - An accurate sense of time contributes to functions ranging from the perception
      and anticipation of sensory events to the production of coordinated movements.
      However, accumulating evidence demonstrates that time perception is subject to
      strong illusory distortion. In two experiments, we investigated whether the
      subjective speed of temporal perception is dependent on our visual environment.
      By presenting human observers with speed-altered movies of a crowded street
      scene, we modulated performance on subsequent production of "20s" elapsed
      intervals. Our results indicate that one's visual environment significantly
      contributes to calibrating our sense of time, independently of any modulation of
      arousal. This plasticity generates an assay for the integrity of our sense of
      time and its rehabilitation in clinical pathologies.

PMID- 21078334
TI  - Solid core column technology applied to HPLC-FD of paralytic shellfish toxins.
AB  - Pre-column oxidation liquid chromatography with fluorescence detection is a
      chemical method for analyzing paralytic shellfish toxins. In order to improve the
      sample throughput and efficiency of AOAC Method 2005.06, solid core particle
      column technology was evaluated. We demonstrate that supplanting the original
      fully porous particle column with a solid core particle column reduces sample
      analysis time from 15 to 5 min per sample and improves resolution.

PMID- 21078335
TI  - Influence of target size and eccentricity on binocular summation of reaction time
      in kinetic perimetry.
AB  - To assess how target size and eccentricity affect binocular summation (BS) of
      reaction time (RT) at suprathreshold level, we measured RT using targets of 0.108
      degrees  and 0.216 degrees  at four eccentricities (0 degrees , 5 degrees , 15
      degrees , 25 degrees ) in six normal volunteers. The difference between the
      monocular/binocular RT differentials for both sizes significantly increased in
      the periphery (P<0.05). The smaller target required significantly longer
      monocular RT at 25 degrees  (P<0.01) and generated greater neural summation than
      the larger target (P<0.01). This suggests that when monocular function has
      reached its limit in visual processing in the periphery, BS increases,
      facilitates visual processing, and shortens binocular RT.

PMID- 21078336
TI  - Aging is associated with quantitative and qualitative changes in circulating cell
      free DNA: the Vitality 90+ study.
AB  - As a marker of cellular death, cell-free DNA (cf-DNA) has a utility in diagnosis
      and prognosis of various disorders. Since aging accompanies increased cellular
      senescence and death, we aimed to characterize potential age-related alterations
      in cf-DNA. The study population consisted of 12 nonagenarian women (participants
      in the Vitality 90+ Study) and 11 healthy control women (aged 22-37 years). Some
      of the nonagenarians (n=8) were also recruited for follow-up after one year. cf
      DNA was extracted using two different methods. Total cf-DNA was quantified
      directly in plasma and the amplifiable cf-DNA was assessed using quantitative
      PCR. Quality of cf-DNA was analysed with a DNA Chip assay. For all the
      quantification methods, the concentration of cf-DNA was significantly higher
      (p<0.05) in nonagenarians as compared to controls. The quality of the cf-DNA also
      displayed a marked difference between nonagenarians and controls; a fragmented
      pattern or appearance of low molecular weight cf-DNA was observed in the majority
      of the nonagenarians, whereas in controls, cf-DNA was intact and had a quasi
      genomic, high molecular weight appearance. In nonagenarians, the quality of cf
      DNA appeared similar in the original and follow-up samples. We propose that some,
      as yet uncharacterized, aspects of aging are reflected in the appearance of cf
      DNA.

PMID- 21078337
TI  - Chaos in the genesis and maintenance of cardiac arrhythmias.
AB  - Dynamical chaos, an irregular behavior of deterministic systems, has been widely
      shown in nature. It also has been demonstrated in cardiac myocytes in many
      studies, including rapid pacing-induced irregular beat-to-beat action potential
      alterations and slow pacing-induced irregular early afterdepolarizations, etc.
      Here we review the roles of chaos in the genesis of cardiac arrhythmias, the
      transition to ventricular fibrillation, and the spontaneous termination of
      fibrillation, based on evidence from computer simulation of mathematical models
      and experiments of animal models.

PMID- 21078338
TI  - Comparative study between n-6, trans and n-3 fatty acids on repeated amphetamine
      exposure: a possible factor for the development of mania.
AB  - In the last decades, foods rich in omega-3 (omega-3) fatty acids (FA) have been
      replaced by omega-6 (omega-6) and trans FA, which are found in processed foods.
      The influence of omega-6 (soybean oil--SO), trans (hydrogenated vegetable fat-
      HVF) and omega-3 (fish oil--FO) fatty acids on locomotor and oxidative stress
      (OS) parameters were studied in an animal model of mania. Rats orally fed with
      SO, HVF and FO for 8 weeks received daily injections of amphetamine (AMPH--4
      mg/kg/mL-ip) for the last week of oral supplementation. HVF induced
      hyperactivity, increased the protein carbonyl levels in the cortex and decreased
      the mitochondrial viability in cortex and striatum. AMPH-treatment increased the
      locomotion and decreased the mitochondrial viability in all groups, but its
      neurotoxicity was higher in the HVF group. Similarly, AMPH administration
      increased the protein carbonyl levels in striatum and cortex of HVF-supplemented
      rats. AMPH reduced the vitamin-C plasmatic levels of SO and HVF-fed rats, whereas
      no change was observed in the FO group. Our findings suggest that trans fatty
      acids increased the oxidative damage per se and exacerbated the AMPH-induced
      effects. The impact of trans fatty acids consumption on neuronal diseases and its
      consequences in brain functions must be further evaluated.

PMID- 21078339
TI  - Behavioural and pharmacological examinations in a transgenic mouse model of early
      onset torsion dystonia.
AB  - Early-onset torsion dystonia is an autosomal dominant movement disorder
      associated with the DYT1 gene (TOR1A) defect which results in a deletion of a
      glutamic acid residue in the protein torsinA. The pathophysiology of dystonia is
      poorly understood. Well characterized animal models can help to give insights
      into the underlying mechanisms and thereby to develop new therapeutics. In the
      present study, we further characterized transgenic DYT1 mice, which were
      initially described to exhibit "dystonia-like" postures. In the present study,
      several behavioural tests in untreated animals did not show strong differences
      between transgenic and control mice, but nearly all transgenic mice showed
      "dystonia-like" postures. However, these movements, also observed in control
      mice, have to be regarded as a clasping reflex. Since dystonia is thought to be
      related to dopaminergic dysfunctions, pharmacological investigations have been
      performed to clarify if dopaminergic substances alter motor behaviour in
      transgenic mice. Chronic treatment with L-DOPA (combined with carbidopa) enhanced
      the hindlimb claspings only in transgenic mice, while acute applications of
      drugs, which exert more selective effects on the dopaminergic system, caused
      similar reactions in transgenic mice and control mice. Therefore, these data do
      not provide clear evidence for dysfunctions of the dopaminergic system in this
      mouse model.

PMID- 21078340
TI  - Does a smoking prevention program in elementary schools prepare children for
      secondary school?
AB  - INTRODUCTION: A smoking prevention program was developed to prepare children in
      elementary school for secondary school. This study assessed the effects on
      smoking in secondary school. METHODS: In 2002, 121 schools in The Netherlands
      were randomly assigned to the intervention or control group. The intervention
      group received 3 lessons in 5th grade of elementary school and a second 3 lessons
      in 6th grade. The control group received "usual care". Students completed 5
      questionnaires: before and after the lessons in 5th and 6th grade and in the
      first class of secondary school. At baseline, 3173 students completed the
      questionnaire; 57% completed all questionnaires. RESULTS: The program had limited
      effect at the end of elementary school. One year later in secondary school
      significant effects on behavioral determinants and smoking were found. The
      intervention group had a higher intention not to smoke (beta=0.13, 95% confidence
      interval=0.01-0.24) and started to smoke less often than the control group (odds
      ratio=0.59, 95% confidence interval=0.35-0.99): smoking increased from 2.5% to
      3.6% in the intervention group and from 3.2% to 6.5% in the control group. Girls
      showed the largest differences in smoking between intervention and control
      condition. CONCLUSIONS: A prevention program in elementary school seems to be
      effective in preventing smoking.

PMID- 21078341
TI  - Immunoglobulin genes and their transcriptional control in teleosts.
AB  - Immunoglobulin (Ig), which exists only in jawed vertebrates, is one of the most
      important molecules in adaptive immunity. In the last two decades, many teleost
      Ig genes have been identified by in silico data mining from the enormous gene and
      EST databases of many fish species. In this review, the organization of Ig gene
      segments, the expressed Ig isotypes and their transcriptional controls are
      discussed. The Ig heavy chain (IgH) locus in teleosts encodes the variable (V),
      the diversity (D), the joining (J) segments and three different isotypic constant
      (C) regions including CMU, Cdelta, and Czeta/tau genes, and is organized as a
      "translocon" type like the IgH loci of higher vertebrates. In contrast, the Ig
      light (L) chain locus is arranged in a "multicluster" or repeating set of VL, JL,
      and CL segments. The IgL chains have four isotypes; two kappa L1/G and L3/F),
      sigma (L2) and lambda. The transcription of IgH genes in teleosts is regulated by
      a VH promoter and the EMU3' enhancer, which both function in a B cell-specific
      manner. The location of the IgH locus, structure and transcriptional function of
      the EMU3' enhancer are important to our understanding of the evolutional changes
      that have occurred in the IgH gene locus.

PMID- 21078342
TI  - Molecular cloning, expression and antiviral activity of porcine interleukin-29
      (poIL-29).
AB  - Human interleukin-29 (IL-29) is a recently discovered cytokine displaying
      antiviral activity against a broad spectrum of viruses, designated as interferon
      (IFN)-lambda1. We here report the molecular cloning, expression and antiviral
      activity of porcine IL-29 (poIL-29). The full-length poIL-29 cDNA sequence
      encoded 191 amino acids with a 19 amino acid signal peptide. Sequence alignments
      showed that poIL-29 had amino acid sequence similarity to wolf (76%), bear (75%),
      horse (75%), orangutan (73%), human (72%), cat (72%) and dog (70%) IL-29. The
      poIL-29 without signal anchor sequence was efficiently expressed as a 6 * HIS
      fusion protein in Escherichia coli and the antiviral activity of the purified
      recombinant protein was 1.8 * 10(3)U/mg protein. The purified recombinant poIL-29
      also exhibited significant antiviral effects against porcine reproductive and
      respiratory syndrome virus and pseudorabies virus in a dose-dependent manner,
      suggesting that poIL-29 is a potential antiviral agent against swine infectious
      diseases.

PMID- 21078343
TI  - Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120
      binding and reactive on formalin-fixed tissue.
AB  - DC-SIGN is a C-type lectin of recognized importance in immunology and in the
      pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN
      have been generated, but their systemic characterization for interfering with
      binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far,
      no anti-DC-SIGN monoclonal antibody has been described that recognizes its
      antigen after formalin fixation and paraffin embedding. In this study, we have
      generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably
      expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing
      antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on
      dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to
      interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin
      fixed dendritic cells and macrophages. Using this antibody we have obtained
      specific labelling of DC-SIGN and colocalisation with the dermal macrophage
      marker CD163 on human skin. The described monoclonal anti-human DC-SIGN
      antibodies will be of use to the scientific community to address fundamental
      immunology issues, in particular concerning macrophages and dendritic cells, and
      help elucidate infection events of pathogen targeting DC-SIGN as recognition
      receptor.

PMID- 21078344
TI  - Development of a modified DNA extraction method for pulsed-field gel
      electrophoresis analysis of Staphylococcus aureus and enterococci without using
      lysostaphin.
AB  - A modified pulsed-field gel electrophoresis (PFGE) protocol was developed and
      applied to clinical isolates of Staphylococcus aureus and enterococci to reduce
      the cost of using lysostaphin. This protocol reduces the expenses of PFGE typing
      of S. aureus and enterococci as it removes the use of lysostaphin during the
      spheroplast formation from these bacteria.

PMID- 21078345
TI  - Optimization of electroporation conditions for Arthrobacter with plasmid PART2.
AB  - A prerequisite for genetic studies of Arthrobacter is a high efficiency
      transformation system that allows for DNA transfer, transposon mutagenesis, and
      expression of specific genes. In this study, we develop a detailed
      electroporation method through a systematic examination of the factors involved
      in the entire electroporation process. Key features of this procedure, including
      the addition of penicillin to cells during the early log phase of growth and the
      presence of 0.5M sorbitol in the electroporation and recovery media, produced the
      greatest increases in transformation efficiency and consistency of results. The
      transformation rate also varied depending on the electrical parameters, DNA
      concentration, and recovery time period. Using optimum conditions, we generally
      achieved an efficiency of 6.8 * 10(7) transformants per microgram of PART2 for
      Arthrobacter sp. A3. This protocol was also successfully applied to other
      Arthrobacter species. Therefore, we conclude that the proposed method is rapid,
      simple and convenient, which allows a transformation trial to be accomplished in
      minutes.

PMID- 21078346
TI  - Real-time impedance analysis of host cell response to meningococcal infection.
AB  - Measuring cell proliferation and cell death during bacterial infection involves
      performing end-point assays that represent the response at a single time point. A
      new technology from Roche Applied Science and ACEA Biosciences allows continuous
      monitoring of cells in real-time using specialized cell culture microplates
      containing micro-electrodes. The xCELLigence system enables continuous
      measurement and quantification of cell adhesion, proliferation, spreading, cell
      death and detachment, thus creating a picture of cell function during bacterial
      infection. Furthermore, lag and log phases can be determined to estimate optimal
      times to infect cells. In this study we used this system to provide valuable
      insights into cell function in response to several virulence factors of the
      meningitis causing pathogen Neisseria meningitidis, including the
      lipopolysaccharide (LPS), the polysaccharide capsule and the outer membrane
      protein Opc. We observed that prolonged time of infection with pathogenic
      Neisseria strains led to morphological changes including cell rounding and loss
      of cell-cell contact, thus resulting in changed electrical impedance as monitored
      in real-time. Furthermore, cell function in response to 14 strains of apathogenic
      Neisseria spp. (N. lactamica and N. mucosa) was analyzed. In contrast, infection
      with apathogenic N. lactamica isolates did not change electrical impedance
      monitored for 48 h. Together our data show that this system can be used as a
      rapid monitoring tool for cellular function in response to bacterial infection
      and combines high data acquisition rates with ease of handling.

PMID- 21078347
TI  - Comparison of methods for measuring viable E. coli cells during cultivation:
      great differences in the early and late exponential growth phases.
AB  - Four methods, namely enumeration of colony-forming units (CFU), aerobic
      respiration, MTT reduction capacity and succinate dehydrogenase activity were
      compared to determine the viability of E. coli cells at the early and late
      exponential growth phases. Our results revealed that great differences in cell
      viability existed between these methods and that the choice of method to
      determine cell viability must be made with caution.

PMID- 21078348
TI  - Clinical care and evolution of paraplegic monkeys (Macaca mulatta) over fourteen
      months post-lesion.
AB  - We have generated a non-human primate model of complete spinal cord injury (SCI)
      with a protracted survival time. Two adult Macaca mulatta underwent complete
      spinal cord transection at T8-T9. We report the effective daily care protocol for
      over one year survival, the health problems we encountered and the treatments
      applied. The animals' cages were customized to maintain them in the best possible
      condition when paraplegic. Daily care, adapted from human care protocols, focused
      mainly on urinary bladder and skin care, and lower limb rehabilitation. The most
      important health problems we faced were skin lesions, in particular from self
      injury to insensitive regions, and urine voiding dysfunction. Skin lesions were
      chronic and severe in one of the monkeys. Serious voiding dysfunction occurred
      temporarily in one monkey in parallel with a high dose oxcarbazepine treatment.
      The main musculoskeletal complications were vertebral column deformities, which
      appeared in both monkeys. The rich experience gathered over the lengthy survival
      period of the two adult paraplegic macaques, the longest to date in the
      literature, should be useful for other scientists willing to study the long term
      physiopathological changes that follow SCI as well as the effects of diverse
      therapeutic strategies before they are applied to humans.

PMID- 21078349
TI  - Modulation of default-mode network activity by acute tryptophan depletion is
      associated with mood change: a resting state functional magnetic resonance
      imaging study.
AB  - Recently, resting-state fMRI (R-fMRI) has attracted interest based on its ability
      to detect the default mode network. We examined the effect of acute tryptophan
      depletion (ATD) on the fractional amplitude of low-frequency fluctuation (fALFF)
      during the resting state, and the correlation between changes of mood and fALFF
      following ATD. We manipulated the central serotonergic levels of 21 right-handed
      healthy males (mean age=21.57+/-1.83 years) following ATD. A within-subjects,
      double-blind, placebo-controlled, and counter-balanced design was employed.
      Following ATD or sham depletion, subjects completed the Profile of Mood States
      (POMS) and underwent 5-min R-fMRI scans. Our findings show that the fALFF of the
      middle orbitofrontal cortex and precuneus was significantly decreased and the
      fALFF of the superior parietal lobule, paracentral lobule and precentral gyrus
      was significantly increased after ATD. The fALFF of the orbitofrontal cortex was
      negatively correlated with depressive mood. The fALFF of the superior parietal
      lobule was positively correlated with anger-hostility and the fALFF of the
      paracentral lobule was negatively correlated with vigor-activity. The middle
      orbitofrontal cortex plays a key role in serotonin depletion-induced brain
      changes and individual differences in depressive mood change. These results serve
      to further elucidate the mechanism of ATD-induced relapse in remitted MDD
      patients.

PMID- 21078350
TI  - The co-speciation of human cytomegalovirus (HCMV) with its human host has enabled
      this human pathogen to evolve multiple mechanisms to allow it to be carried,
      generally sub-clinically, for the lifetime of the host in the face of a robust
      immune response. Preface.

PMID- 21078351
TI  - Endosomal escape pathways for delivery of biologicals.
AB  - Despite continuous improvements in delivery systems, the development of methods
      for efficient and specific delivery of targeted therapeutic agents still remains
      an issue in biological treatments such as protein and gene therapy. The endocytic
      pathway is the major uptake mechanism of cells and any biological agents, such as
      DNA, siRNA and proteins. These agents become entrapped in endosomes and are
      degraded by specific enzymes in the lysosome. Thus, a limiting step in achieving
      an effective biological based therapy is to facilitate the endosomal escape and
      ensure cytosolic delivery of the therapeutics. Bacteria and viruses are pathogens
      which use different mechanisms to penetrate the membranes of their target cells
      and escape the endosomal pathway. Different mechanisms such as pore formation in
      the endosomal membrane, pH-buffering effect of protonable groups and fusion into
      the lipid bilayer of endosomes have been proposed to facilitate the endosomal
      escape. Several viral and bacterial proteins have been identified that are
      involved in this process. In addition, chemical agents and photochemical methods
      to rupture the endosomal membrane have been described. New synthetic biomimetic
      peptides and polymers with high efficacy in facilitating the endosomal escape,
      low pathogenicity and toxicity have been developed. Each strategy has different
      characteristics and challenges for designing the best agents and techniques to
      facilitate the endosomal escape are ongoing. In this review, several mechanisms
      and agents which are involved in endosomal escape are introduced.

PMID- 21078352
TI  - Specific psychological variables predict quality of diet in women of lower, but
      not higher, educational attainment.
AB  - Our previous work found that perceived control over life was a significant
      predictor of the quality of diet of women of lower educational attainment. In
      this paper, we explore the influence on quality of diet of a range of
      psychological and social factors identified during focus group discussions, and
      specify the way this differs in women of lower and higher educational attainment.
      We assessed educational attainment, quality of diet, and psycho-social factors in
      378 women attending Sure Start Children's Centres and baby clinics in
      Southampton, UK. Multiple-group path analysis showed that in women of lower
      educational attainment, the effect of general self-efficacy on quality of diet
      was mediated through perceptions of control and through food involvement, but
      that there were also direct effects of social support for healthy eating and
      having positive outcome expectancies. There was no effect of self-efficacy,
      perceived control or outcome expectancies on the quality of diet of women of
      higher educational attainment, though having more social support and food
      involvement were associated with improved quality of diet in these women. Our
      analysis confirms our hypothesis that control-related factors are more important
      in determining dietary quality in women of lower educational attainment than in
      women of higher educational attainment.

PMID- 21078353
TI  - Addition of positive charges at the C-terminal peptide region of CssII, a
      mammalian scorpion peptide toxin, improves its affinity for sodium channels
      Nav1.6.
AB  - CssII is a beta-scorpion peptide that modifies preferentially sodium currents of
      the voltage-dependent Na(+) channel (Nav) sub-type 1.6. Previously, we have found
      that the C-terminal amidation of CssII increases its affinity for Nav, which
      opens at more negative potentials in the presence of CssII. Although C-terminal
      amidation in vitro conditions is possible, five CssII peptide toxin variants with
      C-terminal residues modified were heterologously expressed (rN66S, rN66H, rN66R,
      r[T64R/N66S] and r[T64R/N66R], in which r stands for recombinant, the capital
      letters to the amino acid residues and the numbers indicate the position of the
      given residue into the primary sequence of the toxin) and correctly folded. A
      secondary structure prediction of CssII agrees with the experimental secondary
      structure obtained by circular dichroism; so all bacterial expressed neurotoxin
      variants maintained the typical alpha/beta secondary structure motif of most
      Na(+) channel scorpion toxins. The electrophysiological properties of all
      recombinant variants were examined, and it was found that substitutions of
      threonine (T) and asparagine (N) at the C-terminal region for arginine (R)
      (r[T64R/N66R]) increase their affinity for Nav1.6. Although, the molecular
      interactions involved in this mechanism are still not clearly determined, there
      is experimental evidence supporting the suspicion that incorporation of basic
      charged amino acid residues at the C-terminal tail of a group of alpha-scorpion
      toxin was favored by natural selection.

PMID- 21078354
TI  - Molecular analysis of antimicrobial agent translocation through the membrane
      porin BpsOmp38 from an ultraresistant Burkholderia pseudomallei strain.
AB  - Burkholderia pseudomallei (Bps) is a Gram-negative bacterium that causes
      melioidosis, an infectious disease of animals and humans common in northern and
      north-eastern parts of Thailand. Successful treatment of melioidosis is difficult
      due to intrinsic resistance of Bps to various antibacterial agents. It has been
      suggested that the antimicrobial resistance of this organism may result from poor
      permeability of the active compounds through porin channels located in the outer
      membrane (OM) of the bacterium. In previous work, a 38-kDa protein, named
      "BpsOmp38", was isolated from the OM of Bps. A topology prediction and liposome
      swelling assay suggested that BpsOmp38 comprises a beta-barrel structure and acts
      as a general diffusion porin. The present study employed black lipid membrane
      (BLM) reconstitution to demonstrate the single-channel conductance of the
      trimeric BpsOmp38 to be 2.7+/-0.3 nS in 1M KCl. High-time resolution BLM
      measurements displayed ion current blockages of seven antimicrobial agents in a
      concentration-dependent manner with the translocation on-rate (kon) following the
      order: norfloxacin?ertapenem>ceftazidime>cefepime>imipenem>meropenem>penicillin
      G. The dwell time of a selected antimicrobial agent (ertapenem) decayed
      exponentially with increasing temperature. The energy barrier for the ertapenem
      binding to the affinity site inside the BpsOmp38 channel was estimated from the
      Arrhenius plot to be 12 kT and for the ertapenem release to be 13 kT at +100 mV.
      The BLM data obtained from this study provide the first insight into
      antimicrobial agent translocation through the BpsOmp38 channel.

PMID- 21078355
TI  - Ginsenoside Rg1 protects against hydrogen peroxide-induced cell death in PC12
      cells via inhibiting NF-kappaB activation.
AB  - Oxidative stress is a major cause in neurodegenerative diseases including
      Alzheimer's disease (AD), Parkinson's disease (PD), and cerebral ischemia.
      Ginsenoside Rg1, a natural product extracted from Panax ginseng C.A. Meyer, has
      been reported to exert notable neuroprotective activities, which partly ascribed
      to its antioxidative activity. However, its molecular mechanism against oxidative
      stress induced by exogenous hydrogen peroxide (H(2)O(2)) remained unclear. In
      this study, we investigated its effect on H(2)O(2)-induced cell death and
      explored possible signaling pathway in PC12 cells. We proved that pretreatment
      with Rg1 at concentrations of 0.1-10 MUM remarkably reduced the cytotoxicity
      induced by 400 MUM of H(2)O(2) in PC12 cells by MTT and Hoechst and PI double
      staining assay. Of note, we demonstrated the activation of NF-kappaB signaling
      pathway induced by H(2)O(2) thoroughly in PC12 cells, and Rg1 suppressed
      phosphorylation and nuclear translocation of NF-kappaB/p65, phosphorylation and
      degradation of inhibitor protein of kappaB (IkappaB) as well as the
      phosphorylation of IkappaB-kinase complex (IKK) by western blotting or indirect
      immunofluorescence assay. Besides, Rg1 also inhibited the activation of Akt and
      the extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the
      protection of Rg1 on H(2)O(2)-injured PC12 cells was attenuated by pretreatment
      with two NF-kappaB pathway inhibitors (JSH-23 or BOT-64). In conclusion, our
      results suggest that Rg1 could rescue the cell injury by H(2)O(2) via down
      regulation NF-kappaB signaling pathway as well as Akt and ERK1/2 activation,
      which put new evidence on the neuroprotective mechanism of Rg1 against the
      oxidative stress and the regulatory role of H(2)O(2) in NF-kappaB pathway in PC12
      cells.

PMID- 21078356
TI  - Acute and subchronic toxicity of FCD, a soybean extract combined with L
      carnitine, in Sprague-Dawley rats.
AB  - Soy products are primarily composed of proteins, phytochemicals such as
      isoflavones, soy lipids, and carbohydrates. Recently, soy isoflavones with L
      carnitine were reported to exhibit anti-obesity effects in mice. FCD, a
      combination of soybean extract and L-carnitine, is a newly developed food
      substance. As a part of its safety assessment, acute and 13-week subchronic
      toxicity studies were performed in a total of 100 Sprague-Dawley (SD) rats. In
      the acute study, a single limit dose of 2000 mg/kg was orally administered to
      five male and five female rats. No adverse effects or mortality was observed
      during a 14-day period or upon gross pathological examination. In the subchronic
      study, FCD was orally administered in daily doses of 500, 1000, and 2000 mg/kg
      for 13 weeks, resulting in no mortality, and no changes in hematological and
      serum biochemistry parameters, gross pathology or histopathology. However, body
      weights of females were significantly decreased 10 weeks after treatment at an
      average of 2000 mg/kg. In addition, a slight decrease in mean food and water
      consumption was observed at the same dose level for 13 weeks. Therefore, the no
      observed-adverse-effect-level (NOAEL) of FCD was considered to be 2000 mg/kg for
      male and 1000 mg/kg for female SD rats.

PMID- 21078357
TI  - Genetic influences of dopamine transport gene on alcohol dependence: a pooled
      analysis of 13 studies with 2483 cases and 1753 controls.
AB  - Previous genetic association studies have reported a possible role of the
      dopamine transporter (DAT, gene symbol: SLC6A3) gene in the etiology of alcohol
      dependence, but the results were conflicting with each other. We conducted a
      pooled analysis of published population-based case-control genetic studies
      investigating associations between polymorphisms in SLC6A3 and alcohol
      dependence. We also explored whether geographic area, ethnicity, gender, and
      diagnostic criteria moderated any association by using stratified analysis.
      Through combining 13 studies with 2483 cases and 1753 controls, the 40-base pair
      variable number tandem repeat (VNTR) in the 3' un-translated region, the well
      studied polymorphism in SLC6A3, did not show any association with alcohol
      dependence in general or in stratified analyses according to geographic area,
      ethnicity, gender, and diagnostic criteria. Due to limited studies focused on
      polymorphisms in other regions of the SLC6A3 gene, we cannot rule out the role of
      the SLC6A3 gene in the involvement of the genetic risk of alcohol dependence.
      Further clarification of the genetic role of SLC6A3 in the susceptibility to
      alcohol dependence should be centered on other potential functional regions of
      the SLC6A3 gene.

PMID- 21078358
TI  - Bioinformatic analysis for allergenicity assessment of Bacillus thuringiensis Cry
      proteins expressed in insect-resistant food crops.
AB  - The novel proteins introduced into the genetically modified (GM) crops need to be
      evaluated for the potential allergenicity before their introduction into the food
      chain to address the safety concerns of consumers. At present, there is no single
      definitive test that can be relied upon to predict allergic response in humans to
      a new protein; hence a composite approach to allergic response prediction is
      described in this study. The present study reports on the evaluation of the Cry
      proteins, encoded by cry1Ac, cry1Ab, cry2Ab, cry1Ca, cry1Fa/cry1Ca hybrid, being
      expressed in Bt food crops that are under field trials in India, for potential
      allergenic cross-reactivity using bioinformatics search tools. The sequence
      identity of amino acids was analyzed using FASTA3 of AllergenOnline version 10.0
      and BLASTX of NCBI Entrez to identify any potential sequence matches to allergen
      proteins. As a step further in the detection of allergens, an independent
      database of domains in the allergens available in the AllergenOnline database was
      also developed. The results indicated no significant alignment and similarity of
      Cry proteins at domain level with any of the known allergens revealing that there
      is no potential risk of allergenic cross-reactivity.

PMID- 21078359
TI  - Pea lectin unfolding reveals a unique molten globule fragment chain.
AB  - Pea lectin (PSL) is a dimeric protein in which each subunit comprises two
      intertwined, post-translationally processed polypeptide chains--a long beta
      fragment and a short alpha-fragment. Using guanidine hydrochloride-induced
      denaturation, we have investigated and characterized the species obtained in the
      unfolding equilibrium of PSL by steady-state and time-resolved fluorescence,
      phosphorescence, and selective chemical modification. During unfolding, the
      fragment chains become separated, and the unfolding pattern reveals a beta
      fragment as intermediate that has the molten globule characteristics. As examined
      by 8-anilino-1-naphthalenesulfonate (ANS) binding, the fragment intermediate
      shows ~20 fold increase in ANS fluorescence, and a large increase in ANS lifetime
      (12.8 ns). The tryptophan environment of the molten globule beta-fragment has
      been probed by selective modification with N-bromosuccinimide (NBS), which shows
      that two tryptophans, possibly Trp 53 and Trp 152 are oxidized while the other
      Trp 128 remains resistant to oxidation. The different types of tryptophan
      environment for the intermediate are supported by phosphorescence studies at 77
      K, which gives a (0,0) band at 410 nm. These results seem to indicate that the
      larger fragment chain of PSL can independently behave as a monomeric or single
      domain protein that undergoes unfolding through intermediate state(s), and may
      provide important insight into the folding problem of oligomeric proteins in
      general and lectins in particular.

PMID- 21078360
TI  - Human adipose tissue-derived mesenchymal stem cells facilitate the
      immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1
      mediated inhibition of NF-kappaB signaling.
AB  - OBJECTIVE: Cyclosporine A (CsA), known as an effective immunosuppressive agent,
      is widely used in clinical fields. Mesenchymal stem cells may exert
      immunomodulatory effects on the immune system, but the exact mechanisms
      underlying them remain controversial. Here we investigated whether human adipose
      tissue-derived mesenchymal stem cells (AMSCs) facilitate in vitro the
      immunomodulatory effects of CsA and we explored the molecule mechanisms that may
      be involved. MATERIALS AND METHODS: Proliferation of T lymphocytes was measured
      by uptake of (3)H-thymidine. Transcription and production of interleukin-2 and
      interferon-gamma were evaluated by real-time quantitative polymerase chain
      reaction, reverse transcription polymerase chain reaction, and enzyme-linked
      immunosorbent assay. Nuclear factor-kappaB (NF-kappaB) was assayed by Western
      blotting and electrophoretic mobility shift assay. Expression of Jagged-1, Jagged
      2, and Delta-1 of AMSCs were surveyed by flow cytometric analysis and Western
      blotting. RESULTS: The combination of moderate-dose AMSCs and low-dose CsA was
      significantly more powerful than moderate-dose AMSCs or large-dose CsA alone in
      suppressing transcription and production of interleukin-2 and interferon-gamma,
      activation of NF-kappaB, and proliferation of T lymphocytes. In addition, AMSCs
      expressed a high level of Jagged-1, which induced activation of Notch signaling
      in T lymphocytes, thus reducing NF-kappaB activity. Anti-Jagged-1 neutralizing
      antibody and N [N-(3, 5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl
      ester could reverse this trend. CONCLUSIONS: Human AMSCs facilitate the
      immunosuppressive effect of CsA on T lymphocytes through Jagged-1/Notch-related
      inhibition of NF-kappaB signaling. The combination of AMSCs and CsA represents a
      rationale therapeutic approach aimed to prevent adverse effects of CsA while
      maintaining its adequate immunosuppressive effect. Expression of Jagged-1 on
      AMSCs may provide an effective mechanism for the immunomodulatory activity of
      AMSCs via direct cell-cell interaction.

PMID- 21078361
TI  - Probabilistic transition from unstable predator-prey interaction to stable
      coexistence of Dictyostelium discoideum and Escherichia coli.
AB  - Predator-prey interactions have been found at all levels within ecosystems.
      Despite their ecological ubiquity and importance, the process of transition to a
      stable coexistent state has been poorly verified experimentally. To investigate
      the stabilization process of predator-prey interactions, we previously
      constructed a reproducible experimental predator-prey system between
      Dictyostelium discoideum and Escherichia coli, and showed that the phenotypically
      changed E. coli contributed to stabilization of the system. In the present study,
      we focused on the transition to stable coexistence of both species after the
      phenotypic change in E. coli. Analysis of E. coli cells isolated from co-culture
      plates as single colony enabled us to readily identify the appearance of
      phenotypically changed E. coli that differed in colony morphology and growth
      rate. It was also demonstrated that two types of viscous colony, i.e., the dense
      type and sparse-type, differing in spatial distribution of both species emerged
      probabilistically and all of the viscous colonies maintained stably were of the
      sparse-type. These results suggest that the phenotypically changed E. coli may
      produce two types of viscous colonies probabilistically. The difference in
      spatial distribution would affect localized interactions between both species and
      then cause probabilistic stabilization of predator-prey interactions.

PMID- 21078362
TI  - Offset response of the olfactory projection neurons in the moth antennal lobe.
AB  - We investigated a population activity of central olfactory neurons after the
      termination of odor input. Olfactory response of projection neurons in the moth
      primary olfactory center was characterized using in vivo intracellular recording
      and staining techniques. The population activity changed rapidly to the different
      states after the stimulus offset. The response after stimulus offset represents
      information regarding odor identity. We analyzed the spatial distribution of
      offset-activated glomeruli in a virtual neuronal population that was
      reconstructed using accumulated individual recordings obtained from different
      specimens. The offset-activated glomeruli tended to be widely distributed,
      whereas the onset-activated glomeruli were relatively clustered. These results
      suggest the importance of lateral interaction in shaping the offset olfactory
      response.

PMID- 21078363
TI  - Computational analysis of the oscillatory dynamics in the processes of CO2
      assimilation and photorespiration.
AB  - The computational analysis of the model system consisting of the processes of CO2
      assimilation and photorespiration shows the appearance of sustained oscillations
      in the system which might reflect their presence in photosynthesizing cells.
      Concentrations of CO2 and O2 oscillate in opposite phases causing Rubisco
      switching continuously between the carboxylase (CO2 assimilation) and the
      oxygenase (photorespiration) reactions. The results of modeling are consistent
      with carbon isotopic and other observed data. They show that the oscillation
      period varies from about 1s to 3s depending on the values of parameters taken.
      Too high concentrations of O2 suppress the oscillations.

PMID- 21078364
TI  - T3 rapidly modulates TSHbeta mRNA stability and translational rate in the
      pituitary of hypothyroid rats.
AB  - Whereas it is well known that T3 inhibits TSHbeta gene transcription, its effects
      on TSHbeta mRNA stability and translation have been poorly investigated. This
      study examined these possibilities, by evaluating the TSHbeta transcripts poly(A)
      tail length, translational rate and binding to cytoskeleton, in pituitaries of
      thyroidectomized and sham-operated rats treated with T3 or saline, and killed 30
      min thereafter. The hypothyroidism induced an increase of TSHbeta transcript
      poly(A) tail, as well as of its content in ribosomes and attachment to
      cytoskeleton. The hypothyroid rats acutely treated with T3 exhibited a reduction
      of TSHbeta mRNA poly(A) tail length and recruitment to ribosomes, indicating that
      this treatment decreased the stability and translation rate of TSHbeta mRNA.
      Nevertheless, acute T3 administration to sham-operated rats provoked an increase
      of TSHbeta transcripts binding to ribosomes. These data add new insight to an
      important role of T3 in rapidly regulating TSH gene expression at
      posttranscriptional level.

PMID- 21078365
TI  - Effect of histamine on the electrophysiology of the human parietal pleura.
AB  - INTRODUCTION: Histamine is involved in the pathogenesis of numerous diseases and
      regulates the permeability of different tissues. The aim of this study is to
      investigate the effects of histamine on the electrophysiology of human parietal
      pleura and the underlying mechanisms involved. MATERIALS AND METHODS: Pleural
      specimens were obtained from patients subjected to thoracic surgery and were
      mounted in Ussing chambers. Histamine solutions (1MUM to 1mM) were applied in
      native and pretreated specimens with dimetindene maleate, cetirizine, ranitidine,
      amiloride and ouabain. Trans-mesothelial resistance was determined (R(TM)).
      RESULTS: Histamine induced a rapid R(TM) increase on the mesothelial (p = 0.008)
      and a decrease on the interstitial surface (p = 0.029). This effect was dose
      dependent and was totally abolished by dimetindene maleate, cetirizine and
      amiloride and partially by ranitidine and ouabain. CONCLUSIONS: Histamine induces
      acute electrochemical changes in human pleura mainly via interaction with the
      H(1) and partially with the H(2) histamine receptors. It also interferes with
      trans-cellular permeability and therefore may participate in pleural fluid
      recycling.

PMID- 21078366
TI  - Steroidogenic factor-1 (SF-1, NR5A1) and human disease.
AB  - Steroidogenic factor-1 (SF-1, Ad4BP, encoded by NR5A1) is a key regulator of
      adrenal and reproductive development and function. Based upon the features found
      in Nr5a1 null mice, initial attempts to identify SF-1 changes in humans focused
      on those rare individuals with primary adrenal failure, a 46,XY karyotype,
      complete gonadal dysgenesis and Mullerian structures. Although alterations
      affecting DNA-binding of SF-1 were found in two such cases, disruption of SF-1 is
      not commonly found in patients with adrenal failure. In contrast, it is emerging
      that variations in SF-1 can be found in association with a range of human
      reproductive phenotypes such as 46,XY disorders of sex development (DSD),
      hypospadias, anorchia, male factor infertility, or primary ovarian insufficiency
      in women. Overexpression or overactivity of SF-1 is also reported in some adrenal
      tumors or endometriosis. Therefore, the clinical spectrum of phenotypes
      associated with variations in SF-1 is expanding and the importance of this
      nuclear receptor in human endocrine disease is now firmly established.

PMID- 21078367
TI  - Melatonin attenuates the amphetamine-induced decrease in vesicular monoamine
      transporter-2 expression in postnatal rat striatum.
AB  - The vesicular monoamine transporter-2 (VMAT-2) is responsible for packaging
      intraneuronal dopamine into synaptic vesicles in preparation for synaptic release
      and is a critical regulator of cytoplasmic dopamine levels and dopaminergic
      function. It has long been recognized that VMAT-2 is also a critical mediator of
      amphetamine-induced dopamine release. Amphetamine-induced lesions during
      development have the potential to produce numerous permanent abnormalities in
      neural circuitry and function. Therefore, in the present study, we investigated
      the effects of amphetamine on the levels of VMAT-2, alpha-synuclein and
      phosphorylated tyrosine hydroxylase in the striatum of neonatal rats. We found
      that chronic amphetamine administration in postnatal rats produces dopaminergic
      deficits in the striatum, including decreases in the levels of VMAT-2 and
      phosphorylated tyrosine hydroxylase. In addition, an increase in alpha-synuclein
      expression was observed in the striatum of postnatal rats following chronic
      amphetamine treatment. Furthermore, we identified a role of (10mg/kg) melatonin,
      a methoxyindole released from the pineal gland, in attenuating the detrimental
      effects of amphetamine on dopaminergic neurons.

PMID- 21078368
TI  - Altered thermal sensitivity in neurons injured by infraorbital nerve lesion.
AB  - Nerve lesions are common injuries. While peripheral sensitivity is lost, the
      partially regenerating nerve undergoes a complex transformation, occasionally
      leading to persistent pain syndromes. Changes of thermal perception following
      nerve injury have received little attention. This study investigates the
      sensitivity of trigeminal neurons after infraorbital nerve lesion in guinea-pigs.
      Cultured trigeminal neurons innervating the area of denervation were identified
      by retrograde transport of DiI deposited at the site of the lesion. The
      standardized protocol consisted of cold and heat stimulation starting from body
      temperature as well as application of menthol and capsaicin, while activation was
      quantified by Fura-2-based calcium microfluorimetry. Compared to neurons from
      control animals, DiI-positive neurons were similar in the percentage and extend
      of the responses to menthol and capsaicin. However, DiI-positive neurons were
      less responsive to cold stimulation and had a lower cold threshold when compared
      to DiI-negative or control neurons. At the same time, DiI-positive neurons were
      more responsive to heat stimulation and had a lower heat threshold compared to
      control neurons. In summary, the percentage of trigeminal neurons responsive to
      thermal or chemical stimulation did not change after axotomy. However, thermal
      sensitivity of these neurons was altered.

PMID- 21078369
TI  - Spontaneous BOLD event triggered averages for estimating functional connectivity
      at resting state.
AB  - Recent neuroimaging studies have demonstrated that the spontaneous brain activity
      reflects, to a large extent, the same activation patterns measured in response to
      cognitive and behavioral tasks. This correspondence between activation and rest
      has been explored with a large repertoire of computational methods, ranging from
      analysis of pairwise interactions between areas of the brain to the global brain
      networks yielded by independent component analysis. In this paper we describe an
      alternative method based on the averaging of the BOLD signal at a region of
      interest (target) triggered by spontaneous increments in activity at another
      brain area (seed). The resting BOLD event triggered averages ("rBeta") can be
      used to estimate functional connectivity at resting state. Using two simple
      examples, here we illustrate how the analysis of the average response triggered
      by spontaneous increases/decreases in the BOLD signal is sufficient to capture
      the aforementioned correspondence in a variety of circumstances. The computation
      of the non linear response during rest here described allows for a direct
      comparison with results obtained during task performance, providing an
      alternative measure of functional interaction between brain areas.

PMID- 21078370
TI  - Dynamics of directed interactions between brain regions during interburst-burst
      EEG patterns in quiet sleep of full-term neonates.
AB  - The study investigates time-variant directed interactions between brain regions
      during the interburst-burst EEG pattern (trace alternant) characteristic of quiet
      sleep in healthy neonates. The transition from interburst to burst is of
      particular interest as the generation of the EEG characteristics at burst onset
      reflects timing and time-variant interplay between the cortical and the thalamo
      cortical brain structures. To study the dynamics of the interactions, time
      variant partial directed coherence (PDC), a measure of effective connectivity,
      was used which allows analysis in the time-frequency range. The main results of
      the grand mean PDC analysis are: (1) PDC time-frequency patterns are frequently
      associated with phase-locked oscillations. (2) Interhemispheric interactions are
      dominant between frontal, central and occipital electrodes and intrahemispheric
      interactions are much less substantial. (3) An interaction breakdown for the
      frequency ranges 1-4 Hz (Fp(1) => Fp(2)) and 0.5-3 Hz (Fp(2) => Fp(1)) exists
      which lasts about 2.5s and which is located at about burst onset. (4) Strong
      interactions in the high-frequency range 3.5-4.5 Hz between the frontal
      electrodes can be observed for both directions at the burst onset. It can be
      concluded that the evolution of strong interactions in the high-frequency range,
      which starts shortly before or at the burst onset from frontal regions to
      anteroposterior directions as well as the frontal interhemispheric interactions,
      are associated with the burst onset generation. Additionally, the collapsing of
      the interactions before burst onset and after the burst are indicative of
      neuronal reorganisation processes.

PMID- 21078371
TI  - Different effects of dopamine D1 receptor on the firing of globus pallidus
      neurons in rats.
AB  - The globus pallidus in rodents, equivalent to the external globus pallidus in
      primates, plays an important role in movement regulation. Morphological studies
      have indicated that the globus pallidus receives dopamine innervation from the
      collaterals of nigrostriatal fibers. To investigate the direct
      electrophysiological effects of dopamine D(1) receptors in the globus pallidus,
      in vivo extracellular recordings were performed in the present study. In 25 out
      of 58 globus pallidus neurons, micro-pressure ejection of 5mM SKF38393 increased
      the spontaneous firing rate from 9.8 +/- 1.9 Hz to 14.3 +/- 2.5 Hz. The average
      increase was 61.5 +/- 8.3% (P<0.001). In another 12 out of the 58 globus pallidus
      neurons, micro-pressure ejection of SKF38393 decreased the spontaneous firing
      rate from 4.7 +/- 1.2 Hz to 2.1 +/- 0.6 Hz. The average decrease was 52.1 +/-
      6.7% (P<0.05). Micro-pressure ejection of SKF38393 did not alter the firing rate
      significantly in the left 21 globus pallidus neurons. The present findings may
      provide a rational for further investigations into the potential of pallidal
      dopamine D(1) receptor in the treatment of Parkinson's disease.

PMID- 21078372
TI  - Detection of acid-sensing ion channel 3 (ASIC3) in periodontal Ruffini endings of
      mouse incisors.
AB  - The acid-sensing ion channel 3 (ASIC3), a member of the epithelial sodium
      channel/degenerin (ENaC/DEG) superfamily, has been reported to participate in
      acid sensing, mechanosensation, and nociception. However, no information is
      available regarding the precise localization and function of this molecule in the
      periodontal ligament, which contains abundant sensory nerves originating from the
      trigeminal ganglion. The present study examined the expression of ASIC3 in the
      lingual periodontal ligament of mouse incisors by immunohistochemistry.
      Furthermore, the expression of ASIC3 in the trigeminal ganglion - which
      innervates the periodontal ligament - was investigated at protein
      (immunohistochemistry and quantitative analysis) and mRNA levels (RT-PCR
      technique and in situ hybridization histochemistry). Immunohistochemistry for
      ASIC3 was able to demonstrate dendritic profiles of the periodontal Ruffini
      endings in the mouse incisors. No thin fibers terminating as nociceptive free
      nerve endings exhibited ASIC3 immunoreactivity. Double immunofluorescent staining
      revealed ASIC3 immunoreaction in the axoplasm but not in the ordinary Schwann
      cells - including the associated terminal Schwann cells. Observation of the
      trigeminal ganglia showed variously sized neurons expressing ASIC3
      immunoreaction; the most intense immunopositivity was found in the small and
      medium-sized neurons, as confirmed by in situ hybridization histochemistry using
      a specific cRNA probe. Quantitative analysis on trigeminal ganglion neurons
      showed that 38.0% of ASIC3 neurons could be categorized as medium-sized neurons
      which mediate mechanotransduction. These findings suggest that ASIC3 functions as
      a molecule for mechanosensation in the periodontal Ruffini endings.

PMID- 21078373
TI  - Long-lasting and transgenerational effects of an environmental enrichment on
      memory formation.
AB  - It has long been believed that genetically determined, but not environmentally
      acquired, phenotypes can be inherited. However, a large number of recent studies
      have reported that phenotypes acquired from an animal's environment can be
      transmitted to the next generation. Moreover, epidemiology studies have hinted
      that a similar phenomenon occurs in humans. This type of inheritance does not
      involve gene mutations that change DNA sequence. Instead, it is thought that
      epigenetic changes in chromatin, such as DNA methylation and histone
      modification, occur. In this review, we will focus on one exciting new example of
      this phenomenon, transfer across generations of enhanced synaptic plasticity and
      memory formation induced by exposure to an "enriched" environment.

PMID- 21078375
TI  - NF-Y and USF1 transcription factor binding to CCAAT-box and E-box elements
      activates the CP27 promoter.
AB  - The maintenance and differentiation of embryonic stem cells (ES cells) depends on
      the regulation of gene expression through the coordinated binding of
      transcription factors to regulatory promoter elements. One of the genes involved
      in embryonic development is the chromatin factor CP27. Previously, we have shown
      that NF-Y interacted with the CP27 proximal promoter CCAAT-box. Here we report
      that CP27 gene expression in mouse ES cells is controlled by CCAAT and E-box cis
      acting regulatory elements and their corresponding transcription factors NF-Y and
      USF1. Specifically, USF1 interacts with the E-box of the CP27 proximal promoter
      and NF-Y interacts with the CCAAT-box. NF-Y and USF1 also interacted with each
      other and activated the CP27 promoter in a synergistic fashion. Together, these
      studies demonstrate that gene expression of the chromatin factor CP27 is
      regulated through the interaction of the transcription factors NF-Y and USF1 with
      the CP27 proximal promoter.

PMID- 21078374
TI  - Protein degradation and memory formation.
AB  - Long-term memories are created when labile short-term memory traces are converted
      to more enduring forms. This process, called consolidation, is associated with
      changes in the synthesis of proteins that alter the biophysical properties of
      neurons and the strength of their synaptic connections. Recently, it has become
      clear that the consolidation process requires not only protein synthesis but also
      degradation. Here, we discuss recent findings on the roles of ubiquitination and
      protein degradation in synaptic plasticity and learning and memory.

PMID- 21078376
TI  - Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most
      likely associated with oxidative stress, p38 MAPK activation, and p53 activation
      in mice.
AB  - Since diabetes induces testicular oxidative damage and cell death, and zinc (Zn)
      plays an important role in the spermatogenesis, the objective of the present
      study was to define the effects of Zn deficiency on diabetes-induced testicular
      apoptosis and associated mechanisms. Zn deficiency was induced by chronic
      treatment of normal and diabetic mice with N,N,N',N'-tetrakis (2-pyridylemethyl)
      ethylenediamine (TPEN) chelation. After diabetes onset, mice were given
      intraperitoneally TPEN at 5mg/kg daily for four months, which, like diabetes,
      induced a significant decrease in testicular Zn level. TUNEL staining revealed
      that testicular apoptosis was significantly increased along with an increased
      Bax/Bcl-2 ratio, in diabetic mice and TPEN-treated normal mice. Zn deficiency
      significantly exacerbated diabetes-induced testicular apoptosis, along with
      significantly increased oxidative and nitrosative damage and down-regulation of
      antioxidant Nrf2 expression. Increased oxidative stress was associated with an
      increase in activation of p38 MAPK and p53 protein in diabetic testis, which was
      worsened in the testes of diabetic mice with Zn deficiency. Diabetes also induced
      a significant increase in endoplasmic reticulum stress and associated cell death,
      which was not affected by Zn deficiency. These results suggest that like
      diabetes, chronic depletion of Zn with TPEN induces testicular oxidative stress
      and damage, along with the activation of p38 MAPK and p53 signaling and
      mitochondria-related apoptotic cell death. Therefore, prevention of Zn deficiency
      for diabetic patients is important in order to avoid the exacerbation of diabetic
      effects on testicular cells death.

PMID- 21078377
TI  - Star-shaped nano-conjugates of cisplatin with high drug payload.
AB  - Core-shell type star polymer bearing carboxylate functions was designed and
      evaluated as nanocarrier of cisplatin. The synthetic route to the star
      macromolecules involved the "core first" method to yield a precursor star polymer
      with a highly branched poly(styrene) core and poly(tert-butyl acrylate) arms. Two
      polymers derived from a common core of M(n) = 2400 g/mol and degrees of
      polymerization of the linear arms 38 and 58 were subjected to acidic hydrolysis
      to obtain stars with a hydrophilic and multifunctional shell. Diffusion ordered
      NMR spectroscopic study revealed that the two products presented single
      populations of stars with values of the apparent hydrodynamic radii 12.9 nm and
      14.0 nm, respectively. The stars were loaded with cisplatin via ligand exchange
      reaction achieving remarkable high drug payload of 45% (w/w). The conjugates were
      stable in an aqueous solution exhibiting no precipitation for a prolonged period
      of time. The release profile of the platinum (II) complexes in phosphate buffered
      saline and RPMI-1640 liquid medium at 37  degrees C indicated sustained manner of
      drug release with no initial burst effect. In vitro cell viability study, using
      four human tumor cell lines proved that the conjugates exhibited lower
      cytotoxicity compared to the free agent. The established cellular accumulation of
      cisplatin indicated uptake of the nanoconjugates by the cells through
      endocytosis.

PMID- 21078378
TI  - Pre- and/or postnatal protein restriction in rats impairs learning and motivation
      in male offspring.
AB  - Suboptimal developmental environments program offspring to lifelong health
      complications including affective and cognitive disorders. Little is known about
      the effects of suboptimal intra-uterine environments on associative learning and
      motivational behavior. We hypothesized that maternal isocaloric low protein diet
      during pregnancy and lactation would impair offspring associative learning and
      motivation as measured by operant conditioning and the progressive ratio task,
      respectively. Control mothers were fed 20% casein (C) and restricted mothers (R)
      10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy
      diet and second letter lactation diet), to evaluate effects of maternal diet on
      male offspring behavior. Impaired learning was observed during fixed ratio-1
      operant conditioning in RC offspring that required more sessions to learn vs. the
      CC offspring (9.4+/-0.8 and 3.8+/-0.3 sessions, respectively, p<0.05).
      Performance in fixed ratio-5 conditioning showed the RR (5.4+/-1.1), CR (4.0+/
      0.8), and RC (5.0+/-0.8) offspring required more sessions to reach performance
      criterion than CC offspring (2.5+/-0.5, p<0.05). Furthermore, motivational
      effects during the progressive ratio test revealed less responding in the RR
      (48.1+/-17), CR (74.7+/-8.4), and RC (65.9+/-11.2) for positive reinforcement vs.
      the CC offspring (131.5+/-7.5, p<0.05). These findings demonstrate negative
      developmental programming effects due to perinatal isocaloric low protein diet on
      learning and motivation behavior with the nutritional challenge in the prenatal
      period showing more vulnerability in offspring behavior.

PMID- 21078379
TI  - Phototoxic effect of TPPS4 and MgTPPS4 on DNA fragmentation of HeLa cells.
AB  - Photodynamic therapy (PDT) is an alternative method of tumour treatment. It is
      based on a photochemical reaction of a photosensitizer, irradiation, and O(2)
      which converts to cytotoxic (1)O(2) and other forms of reactive oxygen species
      (ROS). The comet assay (also called single-cell gel electrophoresis, SCGE) is a
      sensitive, simple and quantitative technique for detection of DNA damage. In our
      study we investigated the phototoxicity of the two porphyrin photosensitizers,
      TPPS4 and MgTPPS4, on HeLa cells. Three different radiation doses and six
      different concentrations of the photosensitizers were used. Our results show that
      the DNA of the cells treated with the TPPS(4) and MgTPPS(4) at the concentrations
      higher than 5 MUM was highly fragmented indicating a strong phototoxic effect
      resulting in a cell apoptosis. On the base of our results we can hypothesize that
      even the irradiation dose of 1 J cm(-2) is sufficient enough to provoke the DNA
      fragmentation.

PMID- 21078380
TI  - A new generation of MDR modulating agents with dual activity: P-gp inhibitor and
      iNOS inducer agents.
AB  - MultiDrug Resistance (MDR) is due to the ability of some ATPase transporters to
      efflux chemotherapeutic agents out from tumor cells decreasing the endocellular
      concentration for the pharmacological effect, causing cancer cells
      chemoresistance. In the present work, a set of MDR modulating agents (MC89, MC70,
      PB28, IG9) able to modulate transmembrane ATP-dependent transporter, P
      glycoprotein (P-gp), and also to induce inducible nitric oxide synthase (iNOS)
      expression in a panel of tumor cell lines are presented. All selected compounds,
      known as potent P-gp modulating agents, stimulated nitric oxide (NO) via iNOS in
      U937, Caco-2 and MCF7-Adr cell lines. The results displayed a new pharmacological
      strategy to revert MDR and lead to develop a new class of MDR reverting agents
      devoid of the limits of P-gp inhibitors third generation.

PMID- 21078381
TI  - Frequent gene hypermethylation in laryngeal cancer cell lines and the resistance
      to demethylation induction by plant polyphenols.
AB  - Promoter hypermethylation is one of the mechanisms in the transcriptional
      inactivation of certain carcinoma - associated genes. In laryngeal cancers
      hypermethylation of tumor suppressor genes is related to their major risk factors
      cigarette smoking and drinking strong alcohols. Since DNA methylation is
      reversible, modulation of the activity of DNA methyltransferases is an
      established therapeutic strategy, which can be also applied in cancer
      chemoprevention. Here, using the MSP procedure, we evaluated the frequency of
      hypermethylation of RARbeta, RASSF1A, HIN-1, GSTP1, MGMT, VHL and DAPK genes in
      several laryngeal and other head and neck squamous cell carcinoma cell lines and
      the effect of various polyphenols on the methylation of RARbeta and MGMT genes in
      the UT-SCC 42B cell line. Most of the cell lines tested were characterized by the
      hypermethylation of at least one of the genes analyzed. The most frequently
      hypermethylated genes were RARbeta and MGMT, while GSTP1 and VHL were not
      methylated in any of the cell lines. None of the tested compounds, including
      decitabine used as a reference compound, changed the methylation of RARbeta and
      MGMT genes. These findings suggest that although hypermethylation of RARbeta and
      MGMT may be considered as potential epigenetic biomarker, their application as
      therapeutic/chemopreventive targets requires further studies.

PMID- 21078382
TI  - Arsenic methylation efficiency increases during the first trimester of pregnancy
      independent of folate status.
AB  - Exposure to inorganic arsenic during pregnancy may negatively influence the
      offspring, though efficient metabolism of arsenic to dimethylarsinic acid (DMA)
      likely reduces the health risks. This study aimed to evaluate methylation of
      arsenic over the entire pregnancy and the influence of nutritional status. We
      studied longitudinally the arsenic metabolite pattern in the urine of 324
      pregnant women exposed to arsenic via drinking water and food in rural
      Bangladesh. Metabolism of arsenic to DMA increased markedly over the course of
      pregnancy, with the greatest improvement occurring in the first trimester, along
      with a marked decrease in the most risk-associated monomethylated metabolite.
      This improvement in methylation was not associated with nutritional status,
      including vitamin B(12) and folate. Efficient methylation to DMA was associated
      with improved urinary excretion of arsenic, relative to blood arsenic
      concentrations, indicating that micronutrient-independent up-regulation of
      arsenic metabolism already in early pregnancy may provide protection for the
      fetus.

PMID- 21078383
TI  - Induction of cell cycle arrest and DNA damage by the HDAC inhibitor panobinostat
      (LBH589) and the lipid peroxidation end product 4-hydroxynonenal in prostate
      cancer cells.
AB  - Histone deacetylase inhibitors (HDACIs) are promising antineoplastic agents for
      the treatment of cancer. Here we report that the lipid peroxidation end product 4
      hydroxynonenal (HNE) significantly potentiates the anti-tumor effects of the HDAC
      inhibitor panobinostat (LBH589) in the PC3 prostate cancer cell model.
      Panobinostat and HNE inhibited proliferation of PC3 cells and the combination of
      the two agents resulted in a significant combined effect. Cell cycle analysis
      revealed that both single agents and, to a greater extent, their combined
      treatment induced G2/M arrest, but cell death occurred in the combined treatment
      only. Furthermore, HNE and, to a greater extent, the combined treatment induced
      dephosphorylation of Cdc2 leading to progression into mitosis as confirmed by
      alpha-tubulin/DAPI staining and phospho-histone H3 (Ser10) analysis. To evaluate
      possible induction of DNA damage we utilized the marker phosphorylated histone
      H2A.X. Results showed that the combination of panobinostat and HNE induced
      significant DNA damage concomitant with the mitotic arrest. Then, by using
      androgen receptor (AR)-expressing PC3 cells we observed that the responsiveness
      to HNE and panobinostat was independent of the expression of functional AR. Taken
      together, our data suggest that HNE potentiates the antitumoral effect of the
      HDACI panobinostat in prostate cancer cells.

PMID- 21078384
TI  - Human prostaglandin H synthase (hPHS)-1- and hPHS-2-dependent bioactivation,
      oxidative macromolecular damage, and cytotoxicity of dopamine, its precursor, and
      its metabolites.
AB  - The dopamine (DA) precursor l-dihydroxyphenylalanine (L-DOPA) and metabolites
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3
      methoxytyramine may serve as substrates for prostaglandin H synthase (PHS)
      catalyzed bioactivation to free radical intermediates. We used CHO-K1 cells
      expressing human (h) PHS-1 or hPHS-2 to investigate hPHS isozyme-dependent
      oxidative damage and cytotoxicity. hPHS-1- and hPHS-2-expressing cells incubated
      with DA, L-DOPA, DOPAC, or HVA exhibited increased cytotoxicity compared to
      untransfected cells, and cytotoxicity was increased further by exogenous
      arachidonic acid (AA), which increased hPHS activity. Preincubation with
      catalase, which detoxifies reactive oxygen species, or acetylsalicylic acid, an
      inhibitor of hPHS-1 and -2, reduced the cytotoxicity caused by DA, L-DOPA, DOPAC,
      and HVA in hPHS-1 and -2 cells both with and without AA. Protein oxidation was
      increased in hPHS-1 and -2 cells exposed to DA or L-DOPA and further increased by
      AA addition. DNA oxidation was enhanced earlier and at lower substrate
      concentrations than protein oxidation in both hPHS-1 and -2 cells by DA, L-DOPA,
      DOPAC, and HVA and further enhanced by AA addition. hPHS-2 cells seemed more
      susceptible than hPHS-1 cells, whereas untransfected CHO-K1 cells were less
      susceptible. Thus, isozyme-specific, hPHS-dependent oxidative damage and
      cytotoxicity caused by neurotransmitters, their precursors, and their metabolites
      may contribute to neurodegeneration associated with aging.

PMID- 21078385
TI  - Combination of PDT and inhibitor treatment affects melanoma cells and spares
      keratinocytes.
AB  - Photodynamic therapy (PDT) is a potential tool in cancer treatment. Today this
      therapy is established among others for the treatment of nonmelanoma skin cancer.
      However, the more dangerous skin cancer--the melanoma--still has to be removed by
      surgery. Therefore, we investigated the effects of PDT and additional
      administration of heme oxygenase I (HO-I) and poly(ADP-ribose) polymerase (PARP)
      inhibitors on the treatment of melanoma cells in comparison to nonmalignant
      keratinocytes. Therefore, cocultures were established with WM451LU melanoma cells
      and HaCaT keratinocytes. In the coculture some 65% melanoma cells and 35% HaCaT
      cells were present before PDT, whereas after PDT the proportion was 41% melanoma
      cells and 59% HaCaT cells. Combination of both inhibitors improves these results
      to only 16% melanoma cells and 84% HaCaT cells. PDT is, therefore, a potent skin
      cancer treatment, which might also be interesting for melanoma treatment. The
      cytotoxic effects of PDT are largely mediated by ROS. Addition of HO-I and PARP
      inhibitors could improve the efficiency of photodynamic treatment.

PMID- 21078386
TI  - Murine in vitro model of the blood-brain barrier for evaluating drug transport.
AB  - In vitro blood-brain barrier (BBB) models help predict brain uptake of potential
      central nervous system drug candidates. Current in vitro models are composed of
      brain microvascular endothelial cells (BMEC) that are isolated from rat, bovine,
      or porcine. However, most in vivo studies on drug transport through the BBB are
      performed in small laboratory animals, specially mouse and thus murine in vitro
      BBB models serve as better surrogates to correlate with these studies. Here we
      describe the functional characterization of a reproducible in vitro model
      composed of murine BMEC co-cultured with rat primary astrocytes in the presence
      of biochemical inducing agents. The co-cultures presented high TEER and low
      sodium fluorescein permeability. Expression of specific BBB tight junction
      proteins (occludin, claudin-5, ZO-1) and the functionality of transporters (Pgp,
      GLUT1) were detected by immunocytochemistry and Western blotting. These results
      indicated a 2.5-fold increase in the expression levels of these proteins in the
      presence of astrocytes. In addition, a high correlation coefficient (0.98) was
      obtained between the permeability of a series of hydrophobic and hydrophilic
      drugs and their corresponding in vivo values. These results together establish
      the utility of this murine model for future drug transport, pathological, and
      pharmacological characterizations of the BBB.

PMID- 21078387
TI  - Potent antimicrobial action of triclosan-lysozyme complex against skin pathogens
      mediated through drug-targeted delivery mechanism.
AB  - Triclosan (TCS), an antimicrobial agent that inhibits bacterial fatty acid
      synthesis by blocking the active site of enoyl-ACP reductase (FabI), is a water
      insoluble agent that limits its therapeutic candidacy. We have recently shown
      that the water solubility and antimicrobial activity of TCS were greatly enhanced
      when complexed to lysozyme (LZ). This study is to examine the therapeutic
      potential of triclosan-lysozyme (T-LZ) complex against common skin pathogens
      expressing different levels of FabI, and to delineate the drug-targeting
      mechanism by lysozyme. The T-LZ exhibited superior antimicrobial activity against
      two bacterial skin pathogens, Propionibacterium acnes and Corynebacterium
      minutissimum, while yeast pathogens, Candida albicans and Malassezia furfur
      lacking FabI enzyme were insensitive to the complex. Unlike free TCS or LZ, the T
      LZ complex exhibited a potent antibacterial activity under a wide range of pH
      condition and salt concentration. Interestingly, P. acnes expressing greater
      amount of FabI was more susceptible to the T-LZ complex than C. minutissimum that
      produces lesser amount of the enzyme. A sensitive assay of FabI activity revealed
      that P. acnes and C. minutissimum treated with the complex exhibited significant
      inhibition of the intracellular FabI activity than cells treated with free TCS,
      indicating the efficiency of lysozyme to specifically deliver TCS to its target
      (FabI) in the cytoplasm of bacterial cells. These results demonstrate, for the
      first time, that lysozyme is a potential drug carrier that allows specific
      targeting to the microbial cells of the water-insoluble triclosan and highlights
      the potency of the complex for the treatment of skin bacterial infections.

PMID- 21078388
TI  - Novel genes differentially expressed between posterior and median silk gland
      identified by SAGE-aided transcriptome analysis.
AB  - Serial analysis of gene expression (SAGE) profiles, from posterior and median
      cells of the silk gland of Bombyx mori, were analyzed and compared, so as to
      identify their respective distinguishing functions. The annotation of the SAGE
      libraries was performed with a B. mori reference tag collection, which was
      extracted from a novel set of Bombyx ESTs, sequenced from the 3' side. Most of
      the tags appeared at similar relative concentration within the two libraries, and
      corresponded with region-specific and highly abundant silk proteins. Strikingly,
      in addition to tags from silk protein mRNAs, 19 abundant tags were found (>=
      0.1%), in the median cell library, which were absent in the posterior cell tag
      collection. With the exception of tags from SP1 mRNA, no PSG specific tags were
      found in this subset class. The analysis of some of the MSG-specific transcripts,
      suggested that middle silk gland cells have diversified functions, in addition to
      their well characterized role in silk sericins synthesis and secretion.

PMID- 21078389
TI  - Citrus, a key insect eggshell protein.
AB  - Molecular aspects of chorion synthesis in insects have been studied deeply in
      species with meroistic ovaries. Information available in insects with panoistic
      ovaries is principally structural whereas molecular information in these species
      is scarce. This paper seeks to balance the above situation by describing a novel
      chorion gene, Citrus, from the cockroach Blattella germanica, a phylogenetically
      basal hemimetabolan insect with reproduction regulated by juvenile hormone and
      with panoistic ovaries. During previous work we discovered a series of novel
      genes which were specifically expressed during chorion formation in B. germanica.
      One of them, herein named Citrus, was peculiar due to its high copy number and
      its very transient expression. In the present paper we characterize Citrus in
      terms of structure and function. The most prominent structural feature is that
      the protein contains a motif which is repeated 33 times encompassing almost all
      the sequence. By using RNAi techniques we have demonstrated that Citrus is a key
      player in the building of the endochorion of B. germanica eggs.

PMID- 21078390
TI  - Structural characteristics of a novel antifreeze protein from the longhorn beetle
      Rhagium inquisitor.
AB  - Antifreeze proteins (AFPs) are characterized by their capacity to inhibit the
      growth of ice and are produced by a variety of polar fish, terrestrial arthropods
      and other organisms inhabiting cold environments. This capacity reflects their
      role as stabilizers of supercooled body fluids. The longhorn beetle Rhagium
      inquisitor is known to express AFPs in its body fluids. In this work we report on
      the primary structure and structural characteristics of a 12.8 kDa AFP from this
      beetle (RiAFP). It has a high capacity to evoke antifreeze activity as compared
      to other known insect AFPs and it is structurally unique in several aspects. In
      contrast to the high content of disulfide bond-formation observed in other
      coleopteran AFPs, RiAFP contains only a single such bond. Six internal repeat
      segments of a thirteen residue repeat pattern is irregularly spaced apart
      throughout its sequence. The central part of these repeat segments is preserved
      as TxTxTxT, which is effectively an expansion of the TxT ice-binding motif found
      in the AFPs of several known insect AFPs.

PMID- 21078391
TI  - The effect of losartan treatment on the response of diabetic cardiomyocytes to
      ATP depletion.
AB  - The present work aimed to investigate the effect of losartan treatment of healthy
      and diabetic rats on cardiomyocyte response to ATP depletion. Cells were isolated
      from normoglycemic (N) and streptozotocin-injected (55 mg/kg) rats (D) treated or
      not treated with losartan (20 mg/kg/day in the drinking water; NL and DL,
      respectively) for 3 weeks. In each group of cells, enzyme activities such as
      glucose-6-phosphate (G6PDH) and glycerol-3-phosphate dehydrogenases (G3PDH),
      lactate/pyruvate, glycogen levels and citrate synthase were measured as an index
      of glycolytic dysregulation and mitochondrial mass, respectively. Cells were then
      challenged with NaCN (2 mM) in glucose-free Tyrode solution (metabolic
      intoxication, MI), a protocol to study ischemia at cell level. Under these
      conditions, the time to contractile failure up to rigor-type hyper-contracture in
      field-stimulated cells and K(ATP) current activation by patch-clamp recordings
      were measured. In comparison with N and NL, D cells presented higher G6PDH and
      cytoplasmic G3PDH activities, lactate/pyruvate, glycogen content but similar
      levels of citrate synthase, and decay time of contraction. When subjected to MI,
      D cells showed delayed activation of the K(ATP) current (25.7+/-7.1 min; p<0.001
      vs. N and NL), increased time to contractile failure and rigor-type hyper
      contracture (p<0.001 vs. N and NL). In cells from DL rats both functional (time
      to rigor and to K(ATP) current activation) and metabolic parameters, approached
      values similar to those measured in N and NL cells. These results demonstrate
      that diabetic cardiomyocytes from rats treated with losartan, maintain the
      capacity to respond promptly to ATP depletion reaching contractile failure, rigor
      type hypercontracture and K(ATP) opening with a similar timing of N cells.

PMID- 21078392
TI  - Using Sculptor and Situs for simultaneous assembly of atomic components into low
      resolution shapes.
AB  - We describe an integrated software system called Sculptor that combines
      visualization capabilities with molecular modeling algorithms for the analysis of
      multi-scale data sets. Sculptor features extensive special purpose visualization
      techniques that are based on modern GPU programming and are capable of
      representing complex molecular assemblies in real-time. The integration of
      graphics and modeling offers several advantages. The user interface not only
      eases the usually steep learning curve of pure algorithmic techniques, but it
      also permits instant analysis and post-processing of results, as well as the
      integration of results from external software. Here, we implemented an
      interactive peak-selection strategy that enables the user to explore a
      preliminary score landscape generated by the colors tool of Situs. The
      interactive placement of components, one at a time, is advantageous for low
      resolution or ambiguously shaped maps, which are sometimes difficult to interpret
      by the fully automatic peak selection of colors. For the subsequent refinement of
      the preliminary models resulting from both interactive and automatic peak
      selection, we have implemented a novel simultaneous multi-body docking in
      Sculptor and Situs that softly enforces shape complementarities between
      components using the normalization of the cross-correlation coefficient. The
      proposed techniques are freely available in Situs version 2.6 and Sculptor
      version 2.0.

PMID- 21078393
TI  - Structure and activity of a functional derivative of Clostridium botulinum
      neurotoxin B.
AB  - Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting
      neurotransmission at cholinergic nerve terminals. BoNTs consist of three
      essential domains for toxicity: the cell binding domain (Hc), the translocation
      domain (Hn) and the catalytic domain (LC). A functional derivative (LHn) of the
      parent neurotoxin B composed of Hn and LC domains was recombinantly produced and
      characterised. LHn/B crystallographic structure at 2.8A resolution is reported.
      The catalytic activity of LHn/B towards recombinant human VAMP was analysed by
      substrate cleavage assay and showed a higher specificity for VAMP-1, -2 compared
      to VAMP-3. LHn/B also showed measurable activity in living spinal cord neurons.
      Despite lacking the Hc (cell-targeting) domain, LHn/B retained the capacity to
      internalize and cleave intracellular VAMP-1 and -2 when added to the cells at
      high concentration. These activities of the LHn/B fragment demonstrate the
      utility of engineered botulinum neurotoxin fragments as analytical tools to study
      the mechanisms of action of BoNT neurotoxins and of SNARE proteins.

PMID- 21078394
TI  - Vibriosis vaccines based on various sero-subgroups of Vibrio anguillarum O2
      induce specific protection in Atlantic cod (Gadus morhua L.) juveniles.
AB  - The purpose of this study was to investigate the efficacy of three monovalent and
      a trivalent vibriosis dip vaccines in juvenile Atlantic cod (Gadus morhua L.),
      examine whether the responses were specific and study the expression of selected
      immune genes after dip vaccination. In addition, the study addressed whether the
      deviating isolates of Vibrio anguillarum serotype O2 belongs to another sero
      subgroup than the previously established sero-subgroups O2a, O2b and O2c. Rabbit
      V. anguillarum serotype O2 antiserum adsorbed with V. anguillarum O2a O-antigen
      was shown, by both ELISA and immunoblotting, to still contain serotype O2
      specific antibodies. Cod V. anguillarum serotype O2 antiserum reacted only with
      isolate of homologous serotype and not with heterologous sero-subgroups. This
      indicates that the deviating V. anguillarum O2 isolates represent a new sero
      subgroup differing from sero-subgroup O2a. The monovalent vaccines included
      formalin inactivated cultures of V. anguillarum sero-subgroup O2a, O2b or
      serotype O2, while the trivalent vaccine contained all three sero-subgroups. Cod
      mounted high protection 7 weeks post dip vaccination with monovalent vaccines
      when challenged with homologous isolates and significantly lower when challenged
      with heterologous isolates, regardless of sero-subgroups. The trivalent vaccine
      resulted in efficient protection against all sero-subgroups tested. Dip
      vaccination of cod juveniles did not result in detectable antibody production or
      alteration in gene expression of the heavy chain of IgM and IgD. In the trivalent
      vaccine group expression of IFNgamma and IL-12p40 were significantly up-regulated
      3 days post vaccination. However, in groups vaccinated against V. anguillarum
      sero-subgroups O2b or O2, IL-12p40 and IFNgamma gene expression were slightly
      increased 3 and 55 days post vaccination, respectively.

PMID- 21078395
TI  - Gene expression and TNF-alpha secretion profile in rainbow trout macrophages
      following exposures to copper and bacterial lipopolysaccharide.
AB  - Fish macrophage function can be altered after exposure to pathogens as well as to
      xenobiotics. Considering that wild and farmed fish can be exposed in their
      habitats simultaneously to different types of stressors, including chemical
      contaminants (e.g. heavy metals) and pathogens (e.g. bacteria), it is fundamental
      to study their impact either isolated or in combination. Therefore, the present
      study aimed to evaluate the effects of copper and bacterial lipopolysaccharide
      (LPS), alone and in combination, on the transcription of target genes related
      with immune system, respiratory burst activity and cell death, using rainbow
      trout macrophages as in vitro model. A cell viability experiment was performed to
      determine the sub-lethal concentrations of copper for rainbow trout macrophages
      and the LC50-24 h was estimated at 60 MUM. The expression of proinflammatory
      cytokines, such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour
      necrosis factor-alpha (TNFalpha) increased after copper and copper plus LPS
      exposure. Copper and LPS interact positively inducing an increase in cytokine
      expression, which may be indicative of an increased inflammatory response.
      However, the increase in TNFalpha mRNA expression induced by 50 MUM copper was
      not accompanied by protein secretion indicating that mRNA abundance does not
      always reflect the level of protein and that the translation of the TNFalpha mRNA
      is somehow inhibited. Serum amyloid A (SAA) and trout C-polysaccharide binding
      protein (TCPBP) mRNA expression also increased after copper, LPS or LPS plus
      copper exposure, indicating a role of acute phase proteins in the local response
      to inflammation. NADPH oxidase and glutathione peroxidase gene expression
      increased in macrophages after 24 h exposure to copper, LPS or LPS plus copper.
      The results from the present study improve the understanding of mechanisms
      involved in copper toxicity, as well as the interaction with a simulated
      inflammatory process.

PMID- 21078396
TI  - Cloning, genomic structure, and expression analysis of peroxiredoxin V from bay
      scallop Argopecten irradians.
AB  - Peroxiredoxins (Prxs) constitute a superfamily of antioxidative proteins that
      play important roles in protecting organisms against damage from reactive oxygen
      species (ROS). In this study, the peroxiredoxin V gene from Argopecten irradians
      (Ai-PrxV) was isolated and characterized. The full-length Ai-PrxV cDNA consists
      of 1689 bp with a 567 bp open reading frame (ORF) that encodes 188 amino acids.
      Three putative polyadenylation consensus signals (AATAAA) were found in the 953
      bp long 3'-UTR. The genomic length of the Ai-PrxV gene is 12575 bp, and it
      contains six exons and five introns. The gene structure is closely related to
      those of chordates but differs from those of arthropods. The 5' flanking region,
      which contains several putative transcription factor binding sites, was also
      analyzed. Quantitative real-time PCR analysis showed that the highest expression
      of the Ai-PrxV transcripts occurred in gill tissue. When challenged with the
      bacteria Vibrio anguillarum, the level of Ai-PrxV transcripts in hemocytes of bay
      scallops was up-regulated and reached the highest point at 15 h post-challenge.
      These results indicate that Ai-PrxV is a constitutive and inducible protein that
      plays an important role in the immune response against bacterial infection.

PMID- 21078397
TI  - Molecular cloning, characterization and expression analysis of interferon-beta
      promoter stimulator 1 (IPS-1) gene from grass carp Ctenopharyngodon idella.
AB  - IPS-1 (interferon-beta promoter stimulator 1), also known as MAVS/VISA/Cardif,
      plays a central role in antiviral immunity. In this manuscript, we cloned and
      characterized IPS-1 from grass carp Ctenopharyngodon idella (designated as CiIPS
      1). The CiIPS-1 cDNA is 2412 bp long and consists of a 5' untranslated region
      (UTR) of 124 bp, a 3' UTR of 497 bp with three cytokine RNA instability motifs
      (ATTTA) and a polyadenylation signal (AATAAA), and an open reading frame (ORF) of
      1791 bp encoding a polypeptide of 596 amino acids with a calculated molecular
      mass of 64.1 kDa and a theoretical isoelectric point of 4.79. Structural analysis
      showed that the CiIPS-1 protein contained an N-terminal CARD (caspase activation
      and recruitment domain), a central proline-rich domain, a putative TRAF2-binding
      motif and a C-terminal transmembrane domain. Similarity analysis of the deduced
      amino acid sequence of the CiIPS-1 by MatGAT software revealed that the CiIPS-1
      shared 27.8-76.4% identity and 47.4-85.2% similarity with other known piscine IPS
      1 sequences. The CiIPS-1 mRNA was constitutively expressed in the examined
      tissues, higher in spleen, and was induced by grass carp reovirus (GCRV)
      injection by semi-quantitative RT-PCR assay. Quantitative real-time RT-PCR
      analysis revealed that the CiIPS-1 mRNA expression was rapidly and significantly
      up-regulated in vivo and in vitro after GCRV infection, and the CiIPS-1
      transcripts were also significantly enhanced in vitro post the synthetic double
      stranded RNA polyinosinic-polycytidylic potassium salt (poly(I:C)) stimulation.
      These results indicated that CiIPS-1 was an inducible acute-phase protein and
      involved in the immune reaction to GCRV in grass carp.

PMID- 21078398
TI  - Subcellular components of probiotics Kocuria SM1 and Rhodococcus SM2 induce
      protective immunity in rainbow trout (Oncorhynchus mykiss, Walbaum) against
      Vibrio anguillarum.
AB  - The efficacy of cellular components of probiotics Kocuria SM1 and Rhodococcus SM2
      to protect rainbow trout (Oncorhynchus mykiss, Walbaum) against vibriosis was
      assessed. Groups of fish (average weight = 10-15 g) were immunized
      intraperitoneally (i.p.) with 0.1 ml of subcellular materials, i.e., 0.2 +/- 0.05
      mg protein per fish, comprising extracellular proteins (ECPs), cell wall proteins
      (CWPs) and whole cell proteins (WCPs) of SM1 and SM2, respectively, or with 0.1
      ml of phosphate-buffered saline (PBS) to serve as the control. Seven days after
      administration, fish from each group were challenged i.p. with 0.1 ml of a
      suspension in PBS of 3 * 10(5) cells ml(-1) per fish of Vibrio anguillarum. Use
      of CWPs and WCPs demonstrated significantly (P < 0.05) better protection against
      V. anguillarum insofar as mortalities were reduced to 11-17% [relative percent
      survival (RPS) = 80-87%], although ECPs fared less well (mortalities = 33-38%;
      RPS = 56-62%; P > 0.05), compared to 86% mortalities of the controls. The mode of
      action reflected activation of innate immune factors by CWPs and WCPs,
      demonstrating significantly (P < 0.05) increased expression of respiratory burst
      (optical density; OD(550 nm)) from 0.039 to 0.043-0.045, peroxidase (OD(550 nm))
      from 0.26 to 0.37-0.55, and bacterial killing activities (i.e., percentage of
      surviving bacteria reduced from 79% to 56-57% for SM2). Moreover, an elevation of
      leucocyte number (from 1.93% to 1.98-2.93%; P > 0.05) and immunoglubolin level
      (from 27 mg ml(-1) to 28.5-33 mg ml(-1); P > 0.05) were observed with the
      experimental groups. These results indicate that cell components of the
      probiotics stimulate an immune response.

PMID- 21078399
TI  - Identification and agglutination properties of hemocyanin from the mud crab
      (Scylla serrata).
AB  - Infectious diseases have significantly delayed the growth of crab aquaculture.
      Identification of the immune molecules and characterization of the defense
      mechanisms will be pivotal to the reduction of these diseases. Hemocyanin is an
      important non-specific immune protein present in the hemolymph of both mollusks
      and arthropods. However, little is known about the hemocyanin from the mud crab
      Scylla serrata. In this study, we identified the S. serrata hemocyanin using
      affinity proteomics and investigated its agglutinative properties. The results
      showed that S. serrata hemocyanin consists of five subunits with molecular
      weights of 70, 72, 75, 76 and 80 kDa, respectively. It demonstrated agglutination
      activities against seven bacterial species at concentrations ranging from 7.5 to
      30 MUg/ml. Agglutination was inhibited by 50-200 mM of N-acetylneuraminic acid,
      alpha-d-glucose, d-galactose and d-xylose. The 76 kDa subunit was identified as
      the protein that primarily binds bacterial cells and we speculate that it
      functions as the agglutinating subunit. We showed that outer membrane proteins
      (Omp) of bacteria could completely inhibit agglutination and that the
      agglutination activities of hemocyanin against Escherichia coli ?OmpA and ?OmpX
      mutants were significantly decreased, suggesting that these two Omps may be
      important ligands of hemocyanin. Together, the data collectively suggests that
      the 76 kDa subunit of S. serrata hemocyanin mediates agglutination through
      recognition of OmpA and OmpX proteins in bacteria.

PMID- 21078400
TI  - Model-free fMRI group analysis using FENICA.
AB  - Exploratory analysis of functional MRI data allows activation to be detected even
      if the time course differs from that which is expected. Independent Component
      Analysis (ICA) has emerged as a powerful approach, but current extensions to the
      analysis of group studies suffer from a number of drawbacks: they can be
      computationally demanding, results are dominated by technical and motion
      artefacts, and some methods require that time courses be the same for all
      subjects or that templates be defined to identify common components. We have
      developed a group ICA (gICA) method which is based on single-subject ICA
      decompositions and the assumption that the spatial distribution of signal changes
      in components which reflect activation is similar between subjects. This
      approach, which we have called Fully Exploratory Network Independent Component
      Analysis (FENICA), identifies group activation in two stages. ICA is performed on
      the single-subject level, then consistent components are identified via spatial
      correlation. Group activation maps are generated in a second-level GLM analysis.
      FENICA is applied to data from three studies employing a wide range of stimulus
      and presentation designs. These are an event-related motor task, a block-design
      cognition task and an event-related chemosensory experiment. In all cases, the
      group maps identified by FENICA as being the most consistent over subjects
      correspond to task activation. There is good agreement between FENICA results and
      regions identified in prior GLM-based studies. In the chemosensory task,
      additional regions are identified by FENICA and temporal concatenation ICA that
      we show is related to the stimulus, but exhibit a delayed response. FENICA is a
      fully exploratory method that allows activation to be identified without
      assumptions about temporal evolution, and isolates activation from other sources
      of signal fluctuation in fMRI. It has the advantage over other gICA methods that
      it is computationally undemanding, spotlights components relating to activation
      rather than artefacts, allows the use of familiar statistical thresholding
      through deployment of a higher level GLM analysis and can be applied to studies
      where the paradigm is different for all subjects.

PMID- 21078401
TI  - Synthesis, characterization, and monkey positron emission tomography (PET)
      studies of [18F]Y1-973, a PET tracer for the neuropeptide Y Y1 receptor.
AB  - Neuropeptide Y receptor subtype 1 (NPY Y1) has been implicated in appetite
      regulation, and antagonists of NPY Y1 are being explored as potential
      therapeutics for obesity. An NPY Y1 PET tracer is useful for determining the
      level of target engagement by NPY Y1 antagonists in preclinical and clinical
      studies. Here we report the synthesis and evaluation of [(18)F]Y1-973, a novel
      PET tracer for NPY Y1. [(18)F]Y1-973 was radiolabeled by reaction of a primary
      chloride with [(18)F]KF/K2.2.2 followed by deprotection with HCl. [(18)F]Y1-973
      was produced with high radiochemical purity (>98%) and high specific activity
      (>1000 Ci/mmol). PET studies in rhesus monkey brain showed that the distribution
      of [(18)F]Y1-973 was consistent with the known NPY Y1 distribution; uptake was
      highest in the striatum and cortical regions and lowest in the pons, cerebellum
      nuclei, and brain stem. Blockade of [(18)F]Y1-973 uptake with NPY Y1 antagonist
      Y1-718 revealed a specific signal that was dose-dependently reduced in all
      regions of grey matter to a similarly low level of tracer uptake, indicative of
      an NPY Y1 specific signal. In vitro autoradiographic studies with [(18)F]Y1-973
      in rhesus monkey and human brain tissue slices revealed an uptake distribution
      consistent with the in vivo PET studies. Highest binding density was observed in
      the dentate gyrus, caudate-putamen, and cortical regions; moderate binding
      density in the hypothalamus and thalamus; and lowest binding density in the
      globus pallidus and cerebellum. In vitro saturation binding studies in rhesus
      monkey and human caudate-putamen homogenates confirmed a similarly high
      B(max)/K(d) ratio for [(18)F]Y1-973, suggesting the tracer may provide a specific
      signal in human brain of similar magnitude to that observed in rhesus monkey.
      [(18)F]Y1-973 is a suitable PET tracer for imaging NPY Y1 in rhesus monkey with
      potential for translation to human PET studies.

PMID- 21078403
TI  - The biogeographical history of the cosmopolitan genus Ranunculus L.
      (Ranunculaceae) in the temperate to meridional zones.
AB  - Ranunculus is distributed in all continents and especially species-rich in the
      meridional and temperate zones. To reconstruct the biogeographical history of the
      genus, a molecular phylogenetic analysis of the genus based on nuclear and
      chloroplast DNA sequences has been carried out. Results of biogeographical
      analyses (DIVA, Lagrange, Mesquite) combined with molecular dating suggest
      multiple colonizations of all continents and disjunctions between the northern
      and the southern hemisphere. Dispersals between continents must have occurred via
      migration over land bridges, or via transoceanic long-distance dispersal, which
      is also inferred from island endemism. In southern Eurasia, isolation of the
      western Mediterranean and the Caucasus region during the Messinian was followed
      by range expansions and speciation in both areas. In the Pliocene and
      Pleistocene, radiations happened independently in the summer-dry western
      Mediterranean-Macaronesian and in the eastern Mediterranean-Irano-Turanian
      regions, with three independent shifts to alpine humid climates in the Alps and
      in the Himalayas. The cosmopolitan distribution of Ranunculus is caused by
      transoceanic and intracontinental dispersal, followed by regional adaptive
      radiations.

PMID- 21078402
TI  - Beyond age and gender: relationships between cortical and subcortical brain
      volume and cognitive-motor abilities in school-age children.
AB  - There is growing evidence that cognitive and motor functions are interrelated and
      may rely on the development of the same cortical and subcortical neural
      structures. However, no study to date has examined the relationships between
      brain volume, cognitive ability, and motor ability in typically developing
      children. The NIH MRI Study of Normal Brain Development consists of a large,
      longitudinal database of structural MRI and performance measures from a battery
      of neuropsychological assessments from typically developing children. This
      dataset provides a unique opportunity to examine relationships between the brain
      and cognitive-motor abilities. A secondary analysis was conducted on data from
      172 children between the ages of 6 to 13 years with up to 2 measurement occasions
      (initial testing and 2-year follow-up). Linear mixed effects modeling was
      employed to account for age and gender effects on the development of specific
      cortical and subcortical volumes as well as behavioral performance measures of
      interest. Above and beyond the effects of age and gender, significant
      relationships were found between general cognitive ability (IQ) and the volume of
      subcortical brain structures (cerebellum and caudate) as well as spatial working
      memory and the putamen. In addition, IQ was found to be related to global and
      frontal gray matter volume as well as parietal gray and white matter. At the
      behavioral level, general cognitive ability was also found to be related to
      visuomotor ability (pegboard) and executive function (spatial working memory).
      These results support the notion that cognition and motor skills may be
      fundamentally interrelated at both the levels of behavior and brain structure.

PMID- 21078404
TI  - Regulation of Angiotensin II receptor signaling by cysteine modification of NF
      kappaB.
AB  - Angiotensin II (Ang II) is a major vasoactive peptide of the renin-angiotensin
      system. Ang II is originally found as one of potent vasoconstrictors, but is now
      attracted attention as an essential mediator of many cardiovascular problems,
      including endothelial dysfunction, arrhythmia and structural remodeling of
      cardiovascular systems. Most of the known pathophysiological effects of Ang II
      are mediated through Ang type1 receptors (AT(1)Rs), and the up-regulation of
      AT(1)Rs is one of important causes by which Ang II can contribute to
      cardiovascular diseases. A growing body of evidence has suggested that reactive
      oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in
      the regulation of AT(1)R signaling. In cardiac fibroblasts, stimulation with
      cytokines or bacterial toxins induces AT(1)R up-regulation through NADPH oxidase
      dependent ROS production. In contrast, nitric oxide (NO) decreases AT(1)R density
      through cysteine modification (S-nitrosylation) of a transcriptional factor,
      nuclear factor kappaB (NF-kappaB). The difference between the effects of ROS and
      NO on AT(1)R expression may be caused by the difference between intracellular
      location of ROS signaling and that of NO signaling, as the agonist-induced S
      nitrosylation of NF-kappaB requires a local interaction between NO synthase (NOS)
      and NF-kappaB in the perinuclear region. Thus, the spatial and temporal
      regulation of cysteine modification by ROS or RNS may underlie the resultant
      changes of AT(1)R signaling induced by agonist stimulation.

PMID- 21078405
TI  - Increased intracellular growth of Mycobacterium avium in HIV-1 exposed monocyte
      derived dendritic cells.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells, and form a
      link between the innate and adaptive immune system. They sample the periphery of
      the body for antigens and present them to T cells to elicit a proper immune
      response. It has been shown that dendritic cells phagocytose mycobacteria, but
      there have been conflicting reports as to whether the bacteria are capable of
      intracellular replication in DCs. Mycobacterium avium is a facultative
      intracellular bacterium, part of the Mycobacterium avium complex (MAC) of
      mycobacteria and are commonly seen as opportunistic pathogens in patients
      infected by Human immunodeficiency virus type 1 (HIV-1). To clarify the issue of
      whether DCs are capable of controlling the intracellular growth of M. avium and
      whether this control is lost upon HIV-1 exposure, we investigated the
      intracellular replication of M. avium in monocyte-derived dendritic cells and
      compared it to bacterial growth in dendritic cultures exposed to HIV-1 for 24 h.
      Our results show that exposure of DCs to HIV-1 promotes or facilitates the
      intracellular growth of M. avium.

PMID- 21078406
TI  - A/H1N1 influenza vaccination in patients with systemic lupus erythematosus:
      safety and immunity.
AB  - OBJECTIVES: To determine the safety of and immunogenicity induced by A/H1N1
      influenza vaccination in patients with systemic lupus erythematosus (SLE).
      RESEARCH DESIGN AND METHODS: The study population comprised 21 SLE patients and
      15 healthy control subjects who underwent split-virion, inactivated monovalent
      A/H1N1 vaccination between December 2009 and January 2010. Sera were obtained
      before, three weeks after, and six months after vaccination. SLE disease activity
      index (SLEDAI) scores and autoantibodies were measured at every visit in SLE
      patients. Haemagglutination inhibition and the serum immunoglobulin G (IgG) level
      were calculated using the World Health Organization (WHO) procedure to evaluate
      the antibody responses. We also recorded current medications and past seasonal
      influenza vaccinations to analyse the interactions between vaccinations and the
      autoimmunity of SLE patients. RESULTS: The mean age of the enrolled population
      was 34.3 years for SLE patients and 39.4 years for control subjects. The average
      SLEDAI score for SLE patients was 4.1 at vaccination, 4.5 at three weeks, and 4.3
      at six months. The seroprotection rate at three weeks was 76.2% in SLE patients
      and 80.0% in healthy control subjects; by six months, the seroprotection rate was
      66.7% in SLE patients and 60% in healthy control subjects. The seroconversion
      rate was 76.2% in SLE patients and 80% in healthy controls at three weeks; by six
      months, the seroconversion rate was 52.4% in SLE patients and 53.3% in healthy
      controls. The response in SLE patients met the criteria of the European Committee
      for Proprietary Medicinal Products guidelines at three weeks, while the
      percentage of seroprotection did not at six months. The clinical disease activity
      and SLEDAI scores did not differ significantly from before to after vaccination
      in SLE patients, although the level of anticardiolipin IgG increased at three
      weeks after vaccination, but with no apparent clinical manifestations.
      CONCLUSIONS: The A/H1N1 influenza vaccine is safe and effective in SLE patients
      and has no obvious adverse clinical effects. Treatment with a single
      immunosuppressive agent or combination therapy also leads to effective humoral
      immunity in these patients.

PMID- 21078407
TI  - Phenylalanine 171 is a molecular brake for translesion synthesis across
      benzo[a]pyrene-guanine adducts by human DNA polymerase kappa.
AB  - Human cells possess multiple specialized DNA polymerases (Pols) that bypass a
      variety of DNA lesions which otherwise would block chromosome replication. Human
      polymerase kappa (Pol kappa) bypasses benzo[a]pyrene diolepoxide-N(2)
      deoxyguanine (BPDE-N(2)-dG) DNA adducts in an almost error-free manner. To better
      understand the relationship between the structural features in the active site
      and lesion bypass by Pol kappa, we mutated codons corresponding to amino acids
      appearing close to the adducts in the active site, and compared bypass
      efficiencies. Remarkably, the substitution of alanine for phenylalanine 171
      (F171), an amino acid conserved between Pol kappa and its bacterial counterpart
      Escherichia coli DinB, enhanced the efficiencies of dCMP incorporation opposite (
      )- and (+)-trans-anti-BPDE-N(2)-dG 18-fold. This substitution affected neither
      the fidelity of TLS nor the efficiency of dCMP incorporation opposite normal
      guanine. This amino acid change also enhanced the binding affinity of Pol kappa
      to template/primer DNA containing (-)-trans-anti-BPDE-N(2)-dG. These results
      suggest that F171 functions as a molecular brake for TLS across BPDE-N(2)-dG by
      Pol kappa and that the F171A derivative of Pol kappa bypasses these DNA lesions
      more actively than does the wild-type enzyme.

PMID- 21078408
TI  - Towards a unifying theory of late stochastic effects of ionizing radiation.
AB  - The traditionally accepted biological basis for the late stochastic effects of
      ionizing radiation (cancer and hereditary disease), i.e. target theory, has so
      far been unable to accommodate the more recent findings of non-cancer disease and
      the so-called non-targeted effects, genomic instability and bystander effect,
      thus creating uncertainty in radiation risk estimation. We propose that ionizing
      radiation can give rise to these effects through two distinct and independent
      routes, one essentially genetic, termed here type A, and the other essentially
      epigenetic, termed type B. Type B processes entail envisaging phenotype as
      represented by a dynamic attractor and radiation acting as an agent that stresses
      cellular processes leading to the adoption of a variant attractor/phenotype.
      Evidence from the literature indicates that type B processes can lead to the
      inheritance of variant cell attractors and mediate a category of trans
      generational effects quite distinct from classical Mendelian inherited disease,
      which is type A. The causal relationships for radiation-induced somatic human
      health detriment, i.e., cancer and non-cancer (e.g., cardiovascular) disease, are
      discussed from the point of view of the proposed classification. This approach
      unifies at a fundamental level the heritable and late somatic effects of
      radiation into a single causal framework that has the potential to be extended to
      the effects of the other environmental agents damaging to health.

PMID- 21078409
TI  - Normalized impact factor (NIF): an adjusted method for calculating the citation
      rate of biomedical journals.
AB  - The interests in journal impact factor (JIF) in scientific communities have grown
      over the last decades. The JIFs are used to evaluate journals quality and the
      papers published therein. JIF is a discipline specific measure and the comparison
      between the JIF dedicated to different disciplines is inadequate, unless a
      normalization process is performed. In this study, normalized impact factor (NIF)
      was introduced as a relatively simple method enabling the JIFs to be used when
      evaluating the quality of journals and research works in different disciplines.
      The NIF index was established based on the multiplication of JIF by a constant
      factor. The constants were calculated for all 54 disciplines of biomedical field
      during 2005, 2006, 2007, 2008 and 2009 years. Also, ranking of 393 journals in
      different biomedical disciplines according to the NIF and JIF were compared to
      illustrate how the NIF index can be used for the evaluation of publications in
      different disciplines. The findings prove that the use of the NIF enhances the
      equality in assessing the quality of research works produced by researchers who
      work in different disciplines.

PMID- 21078410
TI  - Inhibition of vascular endothelial growth factor-induced angiogenesis by
      scopoletin through interrupting the autophosphorylation of VEGF receptor 2 and
      its downstream signaling pathways.
AB  - Our previous studies revealed that scopoletin, the main bioactive constituent of
      Erycibe obtusifolia Benth stems, exerted anti-arthritic activity in vivo partly
      by preventing synovial angiogenesis. Herein we further investigated the anti
      angiogenic potential and related mechanisms of this coumarin compound in vivo and
      in vitro. On chick chorioallantoic membrane (CAM) model, scopoletin (10, 30, 100
      nmol/egg) dose-dependently reduced the blood vessels that were quantified by
      counting the number of blood vessel branch points. In vitro, scopoletin at
      concentrations above 30 microM obviously inhibited the VEGF-induced tube
      formation, proliferation and migration of human umbilical vein endothelial cells
      (HUVECs). Furthermore, scopoletin was shown to block VEGF-induced
      autophosphorylation of VEGFR2 but not VEGFR1, and down-regulate the following
      activation of ERK1/2, p38 MAPK and endothelial nitric oxide synthase (eNOS) as
      well as the production of nitric oxide (NO) in HUVECs. In sum, our findings
      further support that scopoletin is a candidate of angiogenesis inhibitors, and it
      functions by interrupting the autophosphorylation of VEGF receptor 2 (VEGFR2) and
      the downstream signaling pathways.

PMID- 21078413
TI  - Left atrial appendage as a target for reducing strokes: justifiable rationale?
      Safe and effective approaches?

PMID- 21078412
TI  - Novel transitional zone index allows more accurate differentiation between
      idiopathic right ventricular outflow tract and aortic sinus cusp ventricular
      arrhythmias.
AB  - BACKGROUND: Although several ECG algorithms have been proposed for
      differentiating the origins of outflow tract ventricular arrhythmia (OT-VA),
      their accuracy still is limited in cases with cardiac rotation. OBJECTIVE: The
      purpose of this study was to assess whether a novel "cardiac rotation-corrected"
      transitional zone (TZ) index would be a useful marker for differentiating right
      ventricular outflow tract (RVOT) origin from aortic sinus cusp (ASC) origin.
      METHODS: Surface ECGs of OT-VAs with left bundle branch block morphology and
      inferior axis in 112 patients who were successfully ablated in the RVOT (n = 87)
      or the ASC (n = 25) were analyzed. The TZ index was defined according to the site
      of R-wave transition of sinus beats and OT-VAs. RESULTS: The TZ index was
      significantly lower in the ASC origin than in the RVOT origin (-1.2 +/- 0.9 vs
      0.3 +/- 0.7, P <.0001). A cutoff value of the TZ index <0 predicted the ASC
      origin with 88% sensitivity and 82% specificity. The previously reported R-wave
      duration index >= 50% had a high specificity of 85% but a low sensitivity of 44%,
      and R/S-wave amplitude index >= 30% had 68% sensitivity and 79% specificity. The
      area under the curve by receiver operating characteristic curve analysis was 0.90
      for the TZ index, which was significantly higher than the R-wave duration index
      and R/S-wave amplitude index of 0.74 and 0.76, respectively. CONCLUSION: This
      novel TZ index can be a more useful marker for differentiating RVOT origin from
      ASC origin.

PMID- 21078414
TI  - To the editor--left atrial appendage electrical isolation.

PMID- 21078415
TI  - Quantifying the cost in power of ignoring continuous covariate imbalances in
      clinical trial randomization.
AB  - Motivated by potentially serious imbalances of continuous baseline covariates in
      clinical trials, we investigated the cost in statistical power of ignoring the
      balance of these covariates in treatment allocation design for a logistic
      regression model. Based on data from a clinical trial of acute ischemic stroke
      treatment, computer simulations were used to create scenarios varying from the
      best possible baseline covariate balance to the worst possible imbalance, with
      multiple balance levels between the two extremes. The likelihood of each scenario
      occurring under simple randomization was evaluated. The power of the main effect
      test for treatment was examined. Our simulation results show that the worst
      possible imbalance is highly unlikely, but it can still occur under simple random
      allocation. Also, power loss could be nontrivial if balancing distributions of
      important continuous covariates were ignored even if adjustment is made in the
      analysis for important covariates. This situation, although unlikely, is more
      serious for trials with a small sample size and for covariates with large
      influence on primary outcome. These results suggest that attempts should be made
      to balance known prognostic continuous covariates at the design phase of a
      clinical trial even when adjustment is planned for these covariates at the
      analysis.

PMID- 21078416
TI  - The generalizability of participants in Veterans Affairs Cooperative Studies
      Program 474, a multi-site randomized cardiac bypass surgery trial.
AB  - OBJECTIVE: The Department of Veterans Affairs (VA) Cooperative Studies Program
      (CSP) initiated a multi-site randomized trial (CSP 474) to determine graph
      patency between radial artery or saphenous vein grafts in coronary artery bypass
      surgery (CABG). In this paper, we describe the study and compare participants'
      baseline characteristics to non-participants who received CABG surgery in the VA.
      METHOD: We identified our participants in the VA administrative databases along
      with all other CABG patients who did not have a concomitant valve procedure
      between FY2003 and FY2008. We extracted demographic, clinical information and
      organizational information at the time of the surgery from the databases. We
      conducted multiple logistic regression to determine characteristics associated
      with participation at three levels: between participants and non-participants
      within participating sites, between participating sites and non-participating
      sites, between participants and all non-participants. RESULTS: Enrollment ended
      in early 2008. Participants were similar to non-participants across many
      parameters. Likewise, participating sites were also quite similar to non
      participating sites, although participating sites had a higher volume of CABG
      surgery, a lower percentage of CABG patients with a prior inpatient mental health
      admission than non-participating sites. After controlling for site differences,
      CSP 474 participants were younger and had fewer co-morbid conditions than non
      participants. CONCLUSIONS: Participants were significantly younger than non
      participants. Participants also had lower rates of some cardiac-related illness
      including, congestive heart failure, peripheral vascular disease, and
      cerebrovascular disease than non-participants.

PMID- 21078417
TI  - Patterns of radiographic outcomes in early, seropositive rheumatoid arthritis: a
      baseline analysis.
AB  - We examine radiographic profile patterns using clustering algorithms to assess
      progression rates at set time intervals in a rheumatoid arthritis (RA)
      observational study. Hands/feet radiographic scores were analyzed for 190 early,
      seropositive RA patients with >= 3 radiographic observations from a prospective
      cohort. Assessments at 6 months, 1 year, and yearly thereafter were requested for
      demographic, therapeutic, functional, laboratory, radiographic, and clinical
      data. Progression rates for the total sharp scores [erosion (E)+joint space
      narrowing (JSN)] were interpolated for intervals of 0 to 6 months, 6 month-1
      year, 1-2 years, and 2-3 years past first radiographic observation. Patients were
      grouped on their sets of rates by K-median clustering algorithms, and categorical
      group membership was regressed onto baseline characteristics using multinomial
      models. The number of clusters was determined using one-way MANOVA, and baseline
      differences across clusters by Kruskal-Wallis tests. The median RA duration was
      6.1 months, mean age 52 years, median disease activity score (DAS) 4.6, mean
      radiographic observations 4.6 (range 3-8) for this mostly female (77%), Caucasian
      (78%) sample. 3 patterns were determined: increasing (n = 41; 22%), increasing
      then decreasing (n = 41; 22%), and flat (n = 108; 57%). High baseline C-reactive
      protein was associated with a worsening radiographic progression (p < 0.005), as
      were HAQ-DI (p = 0.07), JSN (p < 0.01), and E (p = 0.03). Our conclusions are
      that radiographic progression patterns graphically supplement traditional linear
      rates, and are flexible to use in both clinical and observational studies. The
      identified clusters and rates may correspond better with clinical status and
      treatment over the disease course than linear progression rates alone.

PMID- 21078418
TI  - A study design to investigate the effect of short-form Sun-style Tai Chi in
      improving functional exercise capacity, physical performance, balance and health
      related quality of life in people with Chronic Obstructive Pulmonary Disease
      (COPD).
AB  - The effectiveness of exercise training in people with COPD is well established.
      However, alternative methods of training such as Tai Chi have not been widely
      evaluated. This paper describes the study design of a clinical trial which aims
      to determine if short form Sun-style Tai Chi improves exercise capacity and
      quality of life in people with COPD. METHOD: This randomised controlled trial
      will be conducted with concealed allocation and blinded outcome assessment.
      Participants will be recruited from Concord Repatriation General Hospital,
      Sydney. After baseline measurement, participants will be randomised into either a
      Tai Chi Group or a Control Group. Participants in the Tai Chi Group will undergo
      supervised training twice weekly for twelve weeks. Participants in the Control
      Group will undergo usual medical care. Measurements will be taken at baseline
      (week 0) and after the study period (week 12). The primary outcome measurement is
      endurance walking capacity assessed by the endurance shuttle walk test. Secondary
      outcomes include measures related to peak walking capacity, physical performance,
      balance, muscle strength and quality of life. Details of the physiological
      responses during Tai Chi will be collected in a small cohort to determine the
      training intensity of Sun-style Tai Chi. DISCUSSION: If short form Sun-style Tai
      Chi improves exercise capacity, physical performance and quality of life in
      people with COPD, this would provide an alternate form of exercise training which
      does not require exercise equipment thus making effective exercise training more
      accessible for the large numbers of people with COPD.

PMID- 21078419
TI  - Factors correlated with fatigue in breast cancer patients before, during and
      after adjuvant chemotherapy: the FATSEIN study.
AB  - INTRODUCTION: Breast cancer is by far the most common form of cancer diagnosis in
      women. Cancer treatments are long, complex and often cumbersome with numerous
      side effects. Fatigue is now considered as the most distressing side effect of
      treatment. Fifty-eight percent to 94% of breast cancer patients experience
      fatigue during treatment with adjuvant chemotherapy. OBJECTIVE: The aim of this
      study is to identify the determinants of cancer-related fatigue, and the long
      term effects of the different adjuvant treatments will be explored. RESEARCH
      DESIGN: A prospective longitudinal study in women diagnosed for the first time
      with stage I-IIIA breast cancer and who have undergone surgery, has been designed
      to meet the study aims. Recruitment began in September 2008 and target enrollment
      completion date is December 2010. (clinicaltrials.gov number, NCT01064427). The
      MFI-20 (Multidimensional Fatigue Inventory) and the EORTC QLQ-C30 (European
      Organization for Research and Treatment Quality of Life Questionnaire) will be
      completed, at several times. The follow-up is planned over a 24-month period. We
      studied adjuvant chemotherapy regimens with anthracyclines or with
      anthracycline/taxane combination. The LOR (Life Orientation Test) will be
      completed only at baseline to estimate the level of optimism of the patient and
      the STAI (State-Trait Anxiety Questionnaire) will be filled to measure a stable
      propensity to experience anxiety, and tendencies to perceive stressful situations
      as threatening. OUTCOMES: The knowledge of determinants should facilitate
      screening of fatigue, and its evaluation on consequences on the patients' quality
      of life would allow physicians better help patients cope with the management of
      fatigue according to the adjuvant regimen.

PMID- 21078420
TI  - Evidence of a mechanism for isodicentric chromosome Y formation in a
      45,X/46,X,idic(Y)(p11.31)/46,X,del(Y)(p11.31) mosaic karyotype.
AB  - Abnormalities involving sex chromosomes account for approximately 0.5% of live
      births. The phenotypes of individuals with mosaic cell lines having structural
      aberrations of the X and Y chromosomes are variable and hard to accurately
      predict. Phenotypes associated with sex chromosome mosaicism range from Turner
      syndrome to males with infertility, and often present with ambiguous genitalia.
      Previous studies of individuals with an 45,X/46,X,idic(Y)(p11) karyotype suggest
      that the presence of both cell lines should result from an intermediate, 46,XY
      cell line. Here we report a 2.5 year old female with phenotypic features of
      Turner syndrome with an isodicentric Y chromosome and a cell line with a deleted
      Y with a final karyotype of 45,X/46,X,idic(Y)(p11.31)/46,X,del(Y)(p11.31).
      Fluorescence in situ hybridization (FISH) mapping of the Y chromosome breakpoint
      revealed very low percentages of the deleted Y cells, but suggested a potential
      mechanism for the formation of the isodicentric Y chromosome. To our knowledge,
      the 46,X,del(Y) intermediate cell line in our patient has not been previously
      reported in individuals with mosaic sex chromosome structural abnormalities.

PMID- 21078421
TI  - A statistical approach for the enhanced production of alkaline protease showing
      fibrinolytic activity from a newly isolated Gram-negative Bacillus sp. strain AS
      S20-I.
AB  - An alkaline-fibrinolytic protease-producing bacterial strain (AS-S20-I) isolated
      from a soil sample in Assam was a Gram-negative rod and grown at temperatures
      ranging from 25 to 55  degrees C, and pH 6.5 to 11.0. Taxonomic identification of
      isolated strain by polyphasic approach (phenotypic characterization,
      chemotaxonomic properties, and ribotyping data of the strain) suggested that it
      belongs to the genus Bacillus, for which the name Bacillus sp. strain AS-S20-I
      (MTCC 8961) was proposed. The initial screening by using Plackett-Burman's design
      demonstrated that among the tested factors, casein, ammonium sulphate and pH of
      the medium significantly (p < 0.05) enhanced the protease (fibrinolytic enzyme)
      yield in submerged fermentation. Further optimization of fibrinolytic protease
      production by Bacillus. sp. strain AS-S20-I in SmF by applying RSM was achieved
      as 749.0 * 10(3)UL(-1) in the presence of 3.0% (w/v) casein and 0.12% (w/v)
      ammonium sulphate at pH 10.9 and 45  degrees C. This was a 4.0-fold increase in
      yield compared with that obtained before applying the Plackett-Burman and RSM
      experimental design. The protease preparation preferentially degraded the fibrin
      (specific activity 2408.0 +/- 70.0 U mg(-1); mean +/- S.D.) suggesting that its
      future application in pharmaceutical industry as thrombolytic and anticancer
      drugs is highly promising.

PMID- 21078422
TI  - Markers of bone metabolism in premature myocardial infarction (<= 40 years of
      age).
AB  - INTRODUCTION: Acute myocardial infarction (AMI) at young age is a rare disease
      with a poor prognosis. Bone metabolism parameters such as 1,25 (OH)2 vitamin D3,
      25 (OH) vitamin D3 and osteocalcin have been recently implicated in the
      development of coronary heart disease (CHD). We evaluated the role of these serum
      markers in a study population of very young AMI survivors (<= 40 years). METHODS
      AND RESULTS: We prospectively enrolled 302 subjects into our multi-center case
      control study, including 102 young myocardial infarction patients (<= 40 years)
      and 200 control subjects who were frequency-matched on gender and age in an
      approximate 2:1 ratio per case patient. In the adjusted logistic regression
      analysis, we used baseline laboratory measurements for the first analysis (acute
      phase analysis) and measurements from one-year follow-up visits (stable phase
      analysis). In both, elevated levels of 25 (OH) vitamin D3 (acute phase: OR per
      IQR 2.02, 95% CI 1.13-3.58, p = 0.017; stable phase: OR 4.07, 95% CI 1.8-9.21, p
      = 0.001) and 1,25 (OH)2 vitamin D3 (acute phase: OR 2.82, 95% CI 1.7-4.7, p <
      0.001; stable phase: OR 4.57, 95% CI 2.31-9.05, p < 0.001) were associated with
      premature AMI. Conversely, osteocalcin was inversely associated with premature
      myocardial infarction (acute phase: OR 0.53, 95% CI 0.28-1.03, p = 0.059; stable
      phase: OR 0.26, 95% CI 0.12-0.6, p < 0.001). The observed associations were
      independent of the acute phase of myocardial infarction. CONCLUSION: In our
      study, elevated levels of 25 (OH) vitamin D3 and 1,25 (OH)2 vitamin D3, as well
      as decreased levels of osteocalcin were associated with myocardial infarction in
      very young patients. The precise mechanism and implications of these findings
      will have to be elucidated in future studies.

PMID- 21078423
TI  - Anti-coagulation effect of Fc fragment against anti-beta2-GP1 antibodies in mouse
      models with APS.
AB  - Anti-beta (2)-glycoprotein I (anti-beta2-GP1) is one of the important
      pathogenesis factors responsible for thrombosis formation in patients with
      antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin
      (IVIg) is a common method used to inhibit the abnormal antibody levels and
      decrease the mortality of APS in emergency situations. We hypothesize that the Fc
      fragment of IgG is the molecular structure responsible for these effects. The
      present study investigates the beneficial effects of both recombinant and natural
      human Fc fragments of heterogeneous IgG against human anti-beta2-GP1 antibodies
      in mouse models with APS. Results showed that both recombinant and natural human
      Fc fragments moderately but significantly decreased the levels of serum anti
      beta2-GP1 antibodies and had anti-coagulation effects in human beta2-GP1
      immunized mice. Furthermore, both recombinant and natural human Fc fragments
      inhibited thrombosis formation and decreased mortality in mouse models infused
      intravenously with human anti-beta2GP1 antibodies from patients with APS.
      Findings suggest that the Fc fragment might be one of the active structural units
      of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a
      useful treatment for individuals with APS.

PMID- 21078424
TI  - Why change?

PMID- 21078425
TI  - A cherry blossom moment in the history of heart valve replacement.

PMID- 21078426
TI  - Preventing cardiac remodeling: the combination of cell-based therapy and cardiac
      support therapy preserves left ventricular function in rodent model of myocardial
      ischemia.
AB  - OBJECTIVE: Cellular and mechanical treatment to prevent heart failure each holds
      therapeutic promise but together have not been reported yet. The goal of the
      present study was to determine whether combining a cardiac support device with
      cell-based therapy could prevent adverse left ventricular remodeling, more than
      either therapy alone. METHODS: The present study was completed in 2 parts. In the
      first part, mesenchymal stem cells were isolated from rodent femurs and seeded on
      a collagen-based scaffold. In the second part, myocardial infarction was induced
      in 60 rats. The 24 survivors were randomly assigned to 1 of 4 groups: control,
      stem cell therapy, cardiac support device, and a combination of stem cell therapy
      and cardiac support device. Left ventricular function was measured with biweekly
      echocardiography, followed by end-of-life histopathologic analysis at 6 weeks.
      RESULTS: After myocardial infarction and treatment intervention, the ejection
      fraction remained preserved (74.9-80.2%) in the combination group at an early
      point (2 weeks) compared with the control group (66.2-82.8%). By 6 weeks, the
      combination therapy group had a significantly greater fractional area of change
      compared with the control group (69.2% +/- 6.7% and 49.5% +/- 6.1% respectively,
      P = .03). Also, at 6 weeks, the left ventricular wall thickness was greater in
      the combination group than in the stem cell therapy alone group (1.79 +/- 0.11
      and 1.33 +/- 0.13, respectively, P = .02). CONCLUSIONS: Combining a cardiac
      support device with stem cell therapy preserves left ventricular function after
      myocardial infarction, more than either therapy alone. Furthermore, stem cell
      delivery using a cardiac support device is a novel delivery approach for cell
      based therapies.

PMID- 21078427
TI  - Endothelin-1 is a useful biomarker for early detection of bronchiolitis
      obliterans in lung transplant recipients.
AB  - OBJECTIVES: Bronchiolitis obliterans (BO) is a severe complication limiting long
      term survival after lung transplantation. To date, no cure exists for BO, and the
      mechanisms leading to BO are not well understood. Endothelin-1 (ET-1) is a potent
      mitogenic and profibrotic peptide produced by pulmonary vascular endothelial
      cells that play a role in the pathophysiology of lung allograft dysfunction.
      Whether ET-1 could predict BO syndrome (BOS) development is unknown. METHODS:
      Transbronchial biopsy specimens and serum and bronchoalveolar lavage were
      obtained from 30 lung transplantation patients with and 30 without BOS at 3
      points. The serum and bronchoalveolar lavage ET-1 concentrations were measured by
      enzyme-linked immunosorbent assay, and the ET-1 mRNA expression in the
      transbronchial biopsy specimens was examined using real-time polymerase chain
      reaction. RESULTS: The pretransplant ET-1 serum concentrations were greater in
      the patients with BOS (P = .02); and ET-1 mRNA was significantly upregulated in
      the lung grafts of those with versus those without BOS at 3 and 12 months after
      transplant (P = .01). At 3 and 12 months after transplantation, the ET-1
      concentrations were significantly elevated in the serum (P < .01 and P < .0001,
      respectively) and bronchoalveolar lavage (P < .01 and P = .02, respectively) of
      patients with compared with those without BOS. On logistic regression analysis,
      the pretransplant and 3-month post-transplant serum ET-1 level predicted for BOS
      (odds ratio, 1.01; 95% confidence interval, 1.004-1.025; P < .007; odds ratio,
      2.9; 95% confidence interval, 1.01-8.52; P < .001). The serum ET-1 level at 12
      months was diagnostic for BOS (odds ratio, 3.9; 95% confidence interval, 1.42
      10.80; P = .008). CONCLUSIONS: Elevated serum ET-1 concentrations were predictive
      of BOS, and the assessment of circulating ET-1 might be beneficial in diagnosing
      and monitoring BO.

PMID- 21078428
TI  - Anomalous coronary arteries from the opposite sinus of Valsalva in asymptomatic
      siblings treated with pulmonary arterial translocation.

PMID- 21078429
TI  - Surgical resection of an intravascular superior vena cava primary lipoma.

PMID- 21078430
TI  - Hypothermia and postoperative outcomes: association or causation?

PMID- 21078433
TI  - Spontaneous rupture of the diaphragm: a diagnostic enigma.

PMID- 21078434
TI  - Simplifying robotic mitral valve repair: minimizing sutures with intra-annular
      ring implantation.

PMID- 21078436
TI  - The epidermal growth factor receptor pathway in relation to pelvic lymph node
      metastasis and survival in early-stage cervical cancer.
AB  - The objective of this study is to correlate the expression of epidermal growth
      factor receptor (EGFR) components with clinical behavior of early-stage cervical
      cancer. Tissue samples of 336 consecutive Federation of International
      Gynecologists and Obstetricians stage IB-IIA cervical cancer patients all treated
      primarily by radical surgery were collected. Clinicopathologic and follow-up data
      were prospectively obtained during standard treatment and follow-up. As
      representatives for the EGFR pathway, expression of EGFR, pEGFR, PTEN, pAKT, and
      pERK was assessed by immunohistochemistry on tissue microarrays. Positive
      immunostaining was observed for EGFR in 32.1%, for pEGFR in 21.0%, for PTEN in
      38.3%, for pAKT in 5.3%, and for pERK in 4.3% of tumor samples. Positive EGFR
      immunostaining was associated with squamous cell carcinoma of the cervix (odds
      ratio [OR], 7.41; 95% confidence interval [CI], 3.38-16.23, P < .001), negative
      pEGFR immunostaining with poor differentiation (OR, 0.39; 95% CI, 0.20-0.73, P =
      .004), and negative PTEN immunostaining with metastatic pelvic lymph nodes (OR,
      0.51; 95% CI, 0.30-0.90, P = .019). In multivariate analysis, only pelvic lymph
      node metastasis (hazard ratio, 6.11; 95% CI, 3.46-10.77, P < .001) and poor
      differentiation (hazard ratio, 1.91; 95% CI, 1.12-3.26, P = .018) were related to
      disease-specific survival. In early-stage cervical cancer, loss of PTEN
      expression is associated with pelvic lymph node metastasis, suggesting PTEN to be
      one of the tumor suppressor genes affecting pelvic lymph node metastasis.
      However, expression of EGFR pathway components does not appear to have prognostic
      impact in surgically treated early-stage cervical cancer.

PMID- 21078437
TI  - Opportunistic disorders of the gastrointestinal tract in the age of highly active
      antiretroviral therapy.
AB  - Since the 1996 advent of highly active antiretroviral therapy (HAART) for the
      treatment of HIV/AIDS, the incidence of most opportunistic disorders in the
      developed world has dramatically declined but definitely has not disappeared. The
      number of new yearly HIV infections (about 55,000) and the total number of US
      infections (more than 1.1 million) remain very significant. Post-HAART
      gastrointestinal (GI) symptoms and biopsy results are still common, especially in
      large inner-city hospitals. The same opportunistic GI disorders were diagnosed in
      442 endoscopies performed since 1996 as before, but at about one half the rate.
      The esophagus had the highest rate of positive biopsy results (46%), especially
      due to Candida. Helicobacter pylori infection has become the most common gastric
      infection. The small bowel still showed cytomegalovirus (CMV), cryptosporidia,
      and Mycobacterium avium complex (MAC) infections. In decreasing order, the most
      common large bowel infections were CMV, cryptosporidiosis, MAC, and
      spirochetosis. Cases of adenovirus, bacterial colitis, Kaposi sarcoma, and
      lymphoma were still diagnosed. Rectal biopsy specimens were the least productive.
      Microsporidiosis is now being diagnosed with special stains. Thus, where HIV/AIDS
      is common, it is important to be able to diagnose these GI processes. In addition
      to presenting post-HAART incidences, diagnostic features and aids are described
      for selected entities.

PMID- 21078438
TI  - Expression of master regulatory genes controlling skeletal development in benign
      cartilage and bone forming tumors.
AB  - Recent progress in skeletal molecular biology has led to the clarification of the
      transcriptional mechanisms of chondroblastic and osteoblastic lineage
      differentiation. Three master transcription factors-Sox9, Runx2, and Osterix-were
      shown to play an essential role in determining the skeletal progenitor cells'
      fate. The present study evaluates the expression of these factors in 4 types of
      benign bone tumors-chondromyxoid fibroma, chondroblastoma, osteoid osteoma, and
      osteoblastoma-using immunohistochemistry and tissue microarrays. Osteoid osteoma
      and osteoblastoma showed strong nuclear expression of Osterix and Runx2. In
      contrast, only a few chondroblastomas showed positive nuclear expression of
      Osterix. Strong nuclear expression of Sox9 was detected in all chondroblastomas,
      whereas nearly half of the osteoblastomas showed focal weak cytoplasmic
      expression of Sox9.

PMID- 21078440
TI  - Ammonia-oxidising archaea--physiology, ecology and evolution.
AB  - Nitrification is a microbially mediated process that plays a central role in the
      global cycling of nitrogen and is also of economic importance in agriculture and
      wastewater treatment. The first step in nitrification is performed by ammonia
      oxidising microorganisms, which convert ammonia into nitrite ions. Ammonia
      oxidising bacteria (AOB) have been known for more than 100 years. However,
      metagenomic studies and subsequent cultivation efforts have recently demonstrated
      that microorganisms of the domain archaea are also capable of performing this
      process. Astonishingly, members of this group of ammonia-oxidising archaea (AOA),
      which was overlooked for so long, are present in almost every environment on
      Earth and typically outnumber the known bacterial ammonia oxidisers by orders of
      magnitudes in common environments such as the marine plankton, soils, sediments
      and estuaries. Molecular studies indicate that AOA are amongst the most abundant
      organisms on this planet, adapted to the most common environments, but are also
      present in those considered extreme, such as hot springs. The ecological
      distribution and community dynamics of these archaea are currently the subject of
      intensive study by many research groups who are attempting to understand the
      physiological diversity and the ecosystem function of these organisms. The
      cultivation of a single marine isolate and two enrichments from hot terrestrial
      environments has demonstrated a chemolithoautotrophic mode of growth. Both pure
      culture-based and environmental studies indicate that at least some AOA have a
      high substrate affinity for ammonia and are able to grow under extremely
      oligotrophic conditions. Information from the first available genomes of AOA
      indicate that their metabolism is fundamentally different from that of their
      bacterial counterparts, involving a highly copper-dependent system for ammonia
      oxidation and electron transport, as well as a novel carbon fixation pathway that
      has recently been discovered in hyperthermophilic archaea. A distinct set of
      informational processing genes of AOA indicates that they are members of a
      distinct and novel phylum within the archaea, the 'Thaumarchaeota', which may
      even be a more ancient lineage than the established Cren- and Euryarchaeota
      lineages, raising questions about the evolutionary origins of archaea and the
      origins of ammonia-oxidising metabolism.

PMID- 21078439
TI  - Higher levels of GATA3 predict better survival in women with breast cancer.
AB  - The GATA family members are zinc finger transcription factors involved in cell
      differentiation and proliferation. GATA3 in particular is necessary for mammary
      gland maturation, and its loss has been implicated in breast cancer development.
      Our goal was to validate the ability of GATA3 expression to predict survival in
      breast cancer patients. Protein expression of GATA3 was analyzed on a high
      density tissue microarray consisting of 242 cases of breast cancer. We associated
      GATA3 expression with patient outcomes and clinicopathologic variables.
      Expression of GATA3 was significantly increased in breast cancer, in situ
      lesions, and hyperplastic tissue compared with normal breast tissue. GATA3
      expression decreased with increasing tumor grade. Low GATA3 expression was a
      significant predictor of disease-related death in all patients, as well as in
      subgroups of estrogen receptor-positive or low-grade patients. In addition, low
      GATA3 expression correlated with increased tumor size and estrogen and
      progesterone receptor negativity. GATA3 is an important predictor of disease
      outcome in breast cancer patients. This finding has been validated in a diverse
      set of populations. Thus, GATA3 expression has utility as a prognostic indicator
      in breast cancer.

PMID- 21078441
TI  - Reductive stress in microbes: implications for understanding Mycobacterium
      tuberculosis disease and persistence.
AB  - Mycobacterium tuberculosis (Mtb) is a remarkably successful pathogen that is
      capable of persisting in host tissues for decades without causing disease. Years
      after initial infection, the bacilli may resume growth, the outcome of which is
      active tuberculosis (TB). In order to establish infection, resist host defences
      and re-emerge, Mtb must coordinate its metabolism with the in vivo environmental
      conditions and nutrient availability within the primary site of infection, the
      lung. Maintaining metabolic homeostasis for an intracellular pathogen such as Mtb
      requires a carefully orchestrated series of oxidation-reduction reactions, which,
      if unbalanced, generate oxidative or reductive stress. The importance of
      oxidative stress in microbial pathogenesis has been appreciated and well studied
      over the past several decades. However, the role of its counterpart, reductive
      stress, has been largely ignored. Reductive stress is defined as an aberrant
      increase in reducing equivalents, the magnitude and identity of which is
      determined by host carbon source utilisation and influenced by the presence of
      host-generated gases (e.g. NO, CO, O(2) and CO(2)). This increased reductive
      power must be dissipated for bacterial survival. To recycle reducing equivalents,
      microbes have evolved unique electron 'sinks' that are distinct for their
      particular environmental niche. In this review, we describe the specific
      mechanisms that some microbes have evolved to dispel reductive stress. The
      intention of this review is to introduce the concept of reductive stress, in
      tuberculosis research in particular, in the hope of stimulating new avenues of
      investigation.

PMID- 21078442
TI  - Regulation of CtsR activity in low GC, Gram+ bacteria.
AB  - CtsR is the global transcriptional regulator of the core protein quality networks
      in low GC, Gram+ bacteria. Balancing these networks during environmental stress
      is of considerable importance for moderate survival of the bacteria, and also for
      virulence of pathogenic species. Therefore, inactivation of the CtsR repressor is
      one of the major cellular responses for fast and efficient adaptation to
      different protein stress conditions. Historically, CtsR inactivation was mainly
      studied for the heat stress response, and recently it has been shown that CtsR is
      an intrinsic thermosensor. Moreover, it has been demonstrated that CtsR
      degradation is regulated by a two-step mechanism during heat stress, dependent on
      the arginine kinase activity of McsB. Interestingly, CtsR is also inactivated
      during oxidative stress, but by a thiol-dependent regulatory pathway. These
      observations suggest that dual activity control of CtsR activity has developed
      during the course of evolution.

PMID- 21078443
TI  - Preface. Perinatal HIV infection.

PMID- 21078444
TI  - Foreword. Perinatal HIV infection: time to rejoice or call to action?

PMID- 21078445
TI  - Perinatal HIV and its prevention: progress toward an HIV-free generation.
AB  - This article reviews the epidemiology of perinatal (HIV)-1 in the United States
      in the past 2 decades and the international HIV epidemic among pregnant women and
      their infants. Since the peak of 1700 reported cases of pediatric AIDS in 1992,
      there has been dramatic progress in decreasing perinatal HIV transmission in the
      United States with fewer than 50 new cases of AIDS annually (>96% reduction) and
      fewer than 300 annual perinatal HIV transmissions in 2005. This success has been
      due to use of combination antiretrovirals given to mothers during pregnancy and
      labor/delivery, obstetric interventions that reduce the risk of transmission,
      provision of zidovudine (ZDV) prophylaxis for 6 weeks to HIV-exposed newborns and
      use of formula. Internationally, the burden of mother-to-child HIV transmission
      remains heavy with 2.1 million children less than 15 years of age estimated to be
      living with HIV and 430,000 new HIV infections in infants occurring each year,
      with most cases occurring in Africa. Current international efforts are directed
      at scaling up successful prevention of mother-to-child transmission interventions
      and new research directed at making breastfeeding safer using antiretroviral
      prophylaxis to either mothers or their infants.

PMID- 21078446
TI  - Mother-to-child transmission of HIV: pathogenesis, mechanisms and pathways.
AB  - More than 400,000 children were infected with (HIV-1) worldwide in 2008, or more
      than 1000 children per day. Mother-to-child transmission (MTCT) of HIV-1 is the
      most important mode of HIV acquisition in infants and children. MTCT of HIV-1 can
      occur in utero, intrapartum, and postnatally through breastfeeding. Great
      progress has been made in preventing such transmission, through the use of
      antiretroviral prophylactic regimens to the mother during gestation and labor and
      delivery and to either mother or infant during breast feeding. The timing and
      mechanisms of transmission, however, are multifactorial and remain incompletely
      understood. This article summarizes what is known about the pathogenetic
      mechanisms and routes of MTCT of HIV-1, and includes virologic, immunologic,
      genetic, and mucosal aspects of transmission.

PMID- 21078448
TI  - Diagnosis of HIV: challenges and strategies for HIV prevention and detection
      among pregnant women and their infants.
AB  - Diagnosis and management of perinatally acquired human immunodeficiency virus
      infection poses many challenges in the areas of diagnosis, clinical and
      psychosocial intervention, and public health policy. Diagnostic tests have
      evolved over the years and many are currently used in the perinatal setting.
      Considerable progress has been realized in each of these areas through
      cooperative efforts of laboratory scientists, clinical teams, and stakeholders.
      However, there remain multiple challenges to address in the future.

PMID- 21078449
TI  - Prevention of mother-to-child transmission of HIV: antiretroviral strategies.
AB  - The World Health Organization's Strategic Approaches to the Prevention of HIV
      Infection in Infants includes 4 components: primary prevention of HIV-1
      infection; prevention of unintended pregnancies among HIV-1-infected women;
      prevention of transmission of HIV-1 infection from mothers to children; and
      provision of ongoing support, care, and treatment to HIV-1-infected women and
      their families. This review focuses on antiretrovirals for secondary prevention
      of HIV-1 infection-prevention of HIV-1 transmission from an HIV-1-infected woman
      to her child. Antiretroviral strategies to prevent the mother-to-child
      transmission of HIV-1 in nonbreastfeeding populations comprise antiretroviral
      treatment of HIV-1-infected pregnant women needing antiretrovirals for their own
      health, antiretroviral prophylaxis for HIV-1-infected pregnant women not yet
      meeting criteria for treatment, and antiretroviral prophylaxis for infants of HIV
      1-infected mothers. The review primarily addresses antiretroviral strategies for
      nonbreastfeeding, HIV-1-infected women and their infants in resource-rich
      settings, such as the United States. Antiretroviral strategies to prevent
      antepartum, intrapartum, and early postnatal transmission in resource-poor
      settings are also addressed, albeit more briefly.

PMID- 21078447
TI  - Viral sequence analysis from HIV-infected mothers and infants: molecular
      evolution, diversity, and risk factors for mother-to-child transmission.
AB  - Great progress has been made in understanding the pathogenesis, treatment, and
      transmission of HIV and the factors influencing the risk of mother-to-child
      transmission (MTCT). Many questions regarding the molecular evolution and genetic
      diversity of HIV in the context of MTCT remain unanswered. Further research to
      identify the selective factors governing which variants are transmitted, how the
      compartmentalization of HIV in different cells and tissues contributes to
      transmission, and the influence of host immunity, viral diversity, and
      recombination on MTCT may provide insight into new prevention strategies and the
      development of an effective HIV vaccine.

PMID- 21078450
TI  - Prevention of mother-to-child transmission of HIV-1: the role of cesarean
      delivery.
AB  - The risk of mother-to-child transmission (MTCT) of HIV can be reduced through
      cesarean delivery prior to the onset of labor and prior to rupture of the
      membranes (elective cesarean delivery [ECD]). As a result of this evidence, the
      American College of Obstetricians and Gynecologists and the Department of Health
      and Human Services Panel on Treatment of HIV-Infected Pregnant Women and
      Prevention of Perinatal Transmission developed guidelines recommending ECD for
      HIV-infected women with plasma viral loads of more than 1000 copies/mL. Since the
      release of the recommendations, an increase in ECD has been seen among HIV
      infected women in the United States. This article discusses the evidence on
      efficacy of ECD, current recommendations in the United States, and risks and
      morbidity related to ECD. Although the benefit of ECD in preventing MTCT of HIV
      is substantial, some questions remain. Specifically, the benefit of ECD for women
      with very low viral loads or for women using combination antiretroviral regimens
      is unclear, as is the timeframe after onset of labor or rupture of membranes
      within which ECD will still confer preventive benefits.

PMID- 21078452
TI  - HIV-1 and breastfeeding: biology of transmission and advances in prevention.
AB  - Breastfeeding accounts for about 40% of mother-to-child transmission of HIV-1
      worldwide and carries an estimated risk of transmission of 0.9% per month after
      the first month of breastfeeding. It is recommended that HIV-1-infected women
      completely avoid breastfeeding in settings where safe feeding alternatives exist.
      However, as replacement feeding is not safely available in many parts of the
      world, and because breastfeeding provides optimal nutrition and protection
      against other infant infections, there is intense ongoing research to make
      breastfeeding safe for HIV-1-infected mothers in resource-limited settings. More
      research is needed to determine the optimal duration of breastfeeding, optimal
      weaning practices, and which individual antiretroviral prophylactic regimen is
      best for HIV-1-infected mothers and their infants in a particular setting.

PMID- 21078453
TI  - HIV drug resistance and mother-to-child transmission of HIV.
AB  - This article covers HIV drug resistance among pregnant women and the implications
      of transmission of resistant HIV to the infant. Resistance to antiretroviral
      drugs may be acquired or can emerge while HIV-infected pregnant women are on
      antiretroviral therapy, either before or during pregnancy. Resistance to
      antiretroviral drugs among HIV-infected infants may be acquired from the mother
      in utero or during the intrapartum period. Resistance may also emerge from
      exposure to antiretroviral drugs given to the infant for prophylaxis against HIV
      transmission. In settings where breastfeeding is practiced, ongoing transmission
      of HIV from breastfeeding may lead to transmission of resistant HIV from the
      mother. If the mother is taking antiretroviral drugs while breastfeeding,
      resistance to antiretroviral drugs may emerge in an HIV-infected infant from
      ingestion of antiretroviral drugs via breast milk. The magnitude and implications
      of antiretroviral resistance among HIV-infected pregnant women and HIV-infected
      infants are summarized.

PMID- 21078451
TI  - Immune-based approaches to the prevention of mother-to-child transmission of HIV
      1: active and passive immunization.
AB  - Despite more than 2 decades of research, an effective vaccine that can prevent
      HIV-1 infection in populations exposed to the virus remains elusive. In the
      pursuit of an HIV-1 vaccine, does prevention of exposure to maternal HIV-1 in
      utero, at birth or in early life through breast milk require special
      consideration? This article reviews what is known about the immune mechanisms of
      susceptibility and resistance to mother-to-child transmission (MTCT) of HIV-1 and
      summarizes studies that have used passive or active immunization strategies to
      interrupt MTCT of HIV-1. Potentially modifiable infectious cofactors that may
      enhance transmission and/or disease progression (especially in the developing
      world) are described. An effective prophylactic vaccine against HIV-1 infection
      needs to be deployed as part of the Extended Program of Immunization recommended
      by the World Health Organization for use in developing countries, so it is
      important to understand how the infant immune system responds to HIV-1 antigens,
      both in natural infection and presented by candidate vaccines.

PMID- 21078455
TI  - Clinical care of the exposed infants of HIV-infected mothers.
AB  - Infants born to HIV-infected mothers are at risk for mother-to-child transmission
      of HIV. Since the beginning of the epidemic, medical advances have dramatically
      reduced transmission rates from the mother to the child. Clinical care of the HIV
      exposed infant involves unique management considerations. Clinicians caring for
      these infants must be knowledgeable about postexposure antiretroviral
      prophylaxis, understand the HIV diagnostic testing necessary to determine the
      infant's HIV status, and be able to provide relevant anticipatory guidance. This
      article presents the pertinent management considerations needed for clinicians to
      provide optimal care to the HIV-exposed infant.

PMID- 21078456
TI  - The clinical care of the HIV-1-infected infant.
AB  - Despite well-established strategies to decrease the mother-to-child transmission
      of HIV-1, new perinatal infections continue to occur globally, reflecting marked
      disparities in access to health care. Once HIV-1 infection has been established
      in an infant, the combination of early initiation of antiretroviral therapy and
      prophylaxis against Pneumocystis jiroveci pneumonia is paramount to reducing
      disease progression. This article reviews the recommendations and evidence for
      the treatment of HIV-1-infected infants.

PMID- 21078454
TI  - Survival and health benefits of breastfeeding versus artificial feeding in
      infants of HIV-infected women: developing versus developed world.
AB  - Infant feeding policies for HIV-infected women in developing countries differ
      from policies in developed countries. This article summarizes the epidemiologic
      data on the risks and benefits of various infant feeding practices for HIV
      infected women living in different contexts. Artificial feeding can prevent a
      large proportion of mother-to-child HIV transmission but also is associated with
      increases in morbidity and mortality among exposed-uninfected and HIV-infected
      children. Antiretroviral drugs can be used during lactation and reduce risks of
      transmission. For most of the developing world, the health and survival benefits
      of breastfeeding exceed the risks of HIV transmission, especially when
      antiretroviral interventions are provided.

PMID- 21078457
TI  - Issues of prematurity and HIV infection.
AB  - Prematurity and HIV present a complex challenge, with biologic underpinnings that
      are often confounded by a myriad of other factors that coexist in this high-risk
      population. Furthermore, many of the current management options designed to
      reduce mother-to-infant transmission, including antiretroviral therapy and
      cesarean birth, may each have an independent effect on prematurity. These issues
      notwithstanding, knowledge gained from randomized controlled trials and
      epidemiologic studies has made a significant impact on the approach to this
      challenging public health problem worldwide. This article discusses the
      significance, contribution, and management of perinatal transmission of HIV in
      prematurity.

PMID- 21078458
TI  - Antiretroviral pharmacology: special issues regarding pregnant women and
      neonates.
AB  - Antiretrovirals may be used in pregnant women infected with the HIV and their
      newborns both for treatment of maternal HIV disease and for prevention of mother
      to-child transmission of HIV. More than 25 antiretroviral agents in 5 classes
      have been approved, with new drugs and classes in development. This article
      reviews current knowledge of the pharmacology of these drugs during pregnancy and
      in the newborn period, highlighting those pharmacologic issues critical to the
      safe and effective use of antiretrovirals in these populations.

PMID- 21078459
TI  - A study of the workforce in emergency medicine: 2007 research summary.
AB  - INTRODUCTION: This paper summarizes nurse-specific elements reported in a study
      of the emergency medicine workforce in 2007. METHODS: In 2008, surveys were
      distributed to over 2600 ED medical directors and nurse managers in the United
      States. RESULTS: The response rate was 21% from nurse managers. Registered nurses
      (RN) in staff positions are 37.9 years of age. The most common highest level of
      education is and associate degree (46%). The predominant workforce is RNs with a
      fixed assignment to the emergency department. Geographic relocation (46%) was the
      most common reason cited for resignations. Nurse practitioner positions continue
      to increase. ED volumes continue to increase. Study respondents reported the
      largest increase in urgent care/fast track service areas. Throughput time from
      registration to discharge was reported as 158 minutes. Boarding patients in the
      emergency department is a common practice, and nurse managers reported boarding
      as an issue that impacts quality care 67% of the time. CONCLUSION: ED volumes
      continue to increase significantly. Innovative nurse staffing and retention
      programs are required to meet future challenges of emergency patient care.

PMID- 21078460
TI  - How will you remember 2010?

PMID- 21078461
TI  - When shopping could be dangerous.

PMID- 21078462
TI  - An innovative way to deal with loss.

PMID- 21078463
TI  - Health care providers' evaluations of family presence during resuscitation.
AB  - INTRODUCTION: The benefits of family presence (FP) during resuscitation are well
      documented in the literature, and it is becoming an accepted practice in many
      hospitals. There is sufficient evidence about health care provider (HCP) and
      family attitudes and beliefs about FP and little about the actual outcomes after
      family witnessed resuscitation. The purpose of this study was to evaluate FP at
      resuscitations. METHODS: A descriptive design was used to collect data at an
      academic medical center in the western U.S. There were 106 resuscitations during
      the study period. Family presence was documented on 31 (29%) records. One hundred
      and seventy-four health care provider names were listed on the resuscitation
      records, and 40 names (23%) were illegible or incomplete. The convenience sample
      of 134 HCPs was invited to complete an electronic survey and 65 (49%) responded.
      RESULTS: Respondents indicated that family members were able to emotionally
      tolerate the situation (59%), did not interfere with the care being provided to
      the patient (88%). In addition, team communication was not negatively affected
      (88%). A family facilitator was present 70% of the time, and it was usually a
      registered nurse (41%). Twenty-one narrative comments were summarized to reflect
      the following themes: 1) family presence is beneficial; 2) family presence is
      emotional; 3) a family facilitator is necessary. DISCUSSION: These study findings
      demonstrate that having families present during resuscitations does not
      negatively impact patient care, is perceived to benefit family members and that a
      dedicated family facilitator is an integral part of the process.

PMID- 21078464
TI  - Reunification of the child and caregiver in the aftermath of disaster.

PMID- 21078465
TI  - Alcohol screening, brief intervention, and referral to treatment conducted by
      emergency nurses: an impact evaluation.
AB  - INTRODUCTION: In a quasi-experimental study, control and intervention group
      outcomes were compared following implementation of alcohol screening, brief
      intervention, and referral to treatment (SBIRT) by emergency nurses. The primary
      hypothesis was: Trauma patients who participate in nurse-delivered ED SBIRT will
      have greater reductions in alcohol consumption and fewer alcohol-related
      incidents than those who do not. METHODS: Patients were screened for alcohol use
      and those with risky drinking were randomly assigned to either the intervention
      or usual care group. Those in the intervention group received a brief
      motivational intervention and referral to appropriate follow-up services. Using
      medical and driving history records, subjects' alcohol consumption, alcohol
      related traffic incidents, repeat injuries, and repeat ED visits were compared
      between groups at baseline and three-month follow-up. RESULTS: Alcohol
      consumption decreased by 70% in the intervention group compared to 20% in the
      usual care group. Drinking frequency also decreased in both groups. Fewer
      patients from the intervention group (20%) had recurring ED visits compared to
      patients in the usual care group (31%). DISCUSSION: The SBIRT procedure can
      impact alcohol consumption and potentially reduce injuries and ED visits when
      successfully implemented by staff nurses in the emergency department environment.
      Further research is needed to improve follow-up methods in this hard to reach,
      mobile patient population.

PMID- 21078466
TI  - Strategies to prevent urinary tract infection from urinary catheter insertion in
      the emergency department.

PMID- 21078467
TI  - Recommendations for the use of intraosseous vascular access for emergent and
      nonemergent situations in various healthcare settings: a consensus paper.

PMID- 21078468
TI  - A 3-year-old trauma patient with progressive paralysis.

PMID- 21078470
TI  - "I want to see the doctor": meeting patients' expectations in the emergency
      department.

PMID- 21078471
TI  - A practical approach to safe and effective computerized tomography for emergency
      department patients.

PMID- 21078472
TI  - Alphabet soup: confusion between DTaP and Tdap.

PMID- 21078473
TI  - Myths and stereotypes: how registered nurses screen for intimate partner
      violence.
AB  - INTRODUCTION: Intimate partner violence, sometimes referred to as domestic
      violence, is a prevalent problem in the United States and across the world.
      Emergency nurses are often the first health care providers to ask individuals
      about this health issue and are often the first to offer intervention and
      prevention measures. METHODS: This study used a phenomenological qualitative
      approach to examine the role of the registered nurse in the emergency setting as
      it relates to intimate partner violence. Thirteen emergency nurses from the South
      Central United States were interviewed for this study. RESULTS: Four major themes
      emerged during analysis of the interviews. The 4 themes were (1) myths,
      stereotypes, and fears; (2) demeanor; (3) frustrations; and (4) safety benefits.
      DISCUSSION: This study suggests that emergency nurses are not screening for
      intimate partner violence based on a protocol as suggested by many professional
      organizations but rather are screening certain patients for violence based on the
      nurses' perception of whether particular patients are likely to be victims of
      violence.

PMID- 21078474
TI  - Evidence-based practice: a debate.

PMID- 21078476
TI  - Minimizing the risk for teen drivers.

PMID- 21078475
TI  - A geriatric patient with medication-mediated profound weakness.

PMID- 21078477
TI  - Conflict sensitivity in International Emergency Nursing.

PMID- 21078478
TI  - Cutting-edge discussions of management, policy, and program issues in emergency
      care.

PMID- 21078479
TI  - Let the games begin.

PMID- 21078480
TI  - Pediatric rash and joint pain: a case review.

PMID- 21078481
TI  - Herbal hallucinations: common abuse situations seen in the emergency department.

PMID- 21078482
TI  - Blunt cardiac trauma.

PMID- 21078483
TI  - Triage nurses influence safety by cutting the color: removal of non-health care
      colored wristbands reduces risk for error.

PMID- 21078484
TI  - [Osteoarthritis: what are the challenges in 2010?].

PMID- 21078486
TI  - Patient-subjective cosmetic outcomes following the varying stages of tissue
      expander breast reconstruction: the importance of completion.
AB  - INTRODUCTION: Tissue expander breast reconstruction consists of three major
      surgical steps: placement of the expander after mastectomy, exchange of the
      expander for an implant, and nipple-areola complex reconstruction. The evolution
      of patient satisfaction throughout this process has not been evaluated. Here we
      performed a stratified analysis of patient-subjective cosmetic outcomes during
      the stages of breast reconstruction. METHODS: Twenty-eight consecutive tissue
      expander-implant reconstructions were performed by the senior author using human
      acellular dermis. Cosmetic outcomes were assessed after each reconstructive stage
      using a validated Breast Evaluation Questionnaire consisting of questions related
      to breast size, shape and firmness in three separate contexts: intimate or sexual
      activities, leisure or social activities, and professional or job-related
      activities. RESULTS: Eighteen patients underwent unilateral reconstruction, while
      10 underwent bilateral reconstruction. Satisfaction scores were statistically
      higher following Stage I and II procedures for bilateral reconstructions. For
      unilateral reconstructions, there was a statistically significant elevation in
      scores following Stage II. The addition of nipple-areola reconstruction resulted
      in the highest scores for both unilateral and bilateral reconstructions. These
      score elevations were significant (p < 0.05) in nearly every measured context for
      unilateral reconstructions and as such, the significant differences in scores
      between unilateral and bilateral cohorts after stages I and II were nearly
      eliminated after completion of the entire reconstructive process. CONCLUSION:
      Satisfaction with tissue expander reconstruction is significantly affected by the
      patients' stage during the reconstructive process. Completion of all three
      stages, including nipple-areolar complex reconstruction, achieves maximal patient
      satisfaction. For unilateral reconstructions, completion of the entire
      reconstructive process, including contralateral symmetry procedures and nipple
      areolar complex reconstruction, results in cosmesis scores that are similar to
      those in bilateral cases.

PMID- 21078485
TI  - CD105 (Endoglin) expression in breast carcinoma effusions is a marker of poor
      survival.
AB  - We analyzed the expression and clinical role of endoglin (CD105) in breast
      carcinoma effusions. Endoglin levels were measured in 36 effusion supernatants by
      ELISA and studied for association with the cancer-associated markers
      calprotectin, VEGF, and the VEGF receptor sFlt1. Endoglin expression was further
      studied in 46 effusions and 22 primary carcinomas using immunohistochemistry. The
      four secreted molecules were detected in all specimens and their levels
      significantly correlated (p < 0.001). In effusions, endoglin was localized to
      carcinoma cells and reactive mesothelium using immunohistochemistry. Tumor cell
      expression was higher in effusions compared to primary carcinomas (p = 0.025),
      and in post-chemotherapy compared to pre-chemotherapy effusions (p = 0.017).
      Higher tumor endoglin expression was associated with poor overall (p = 0.021) and
      disease-free (p = 0.032) survival in univariate analysis, and was an independent
      predictor in Cox multivariate analysis (p = 0.001 and p = 0.038, respectively).
      Our data suggest that endoglin may be an important therapeutic target in
      metastatic breast cancer.

PMID- 21078487
TI  - Breastfeeding in breast cancer survivors: pattern, behaviour and effect on breast
      cancer outcome.
AB  - Little is known regarding the safety and feasibility of breastfeeding in women
      with a history of breast cancer. We have performed a survey among breast cancer
      patients who completed their pregnancy following breast cancer management to
      examine their lactation behaviours and its effect on breast cancer outcome. Out
      of 32 women identified, 20 were reachable and accepted to take the questionnaire.
      Ten women initiated breastfeeding, 4 stopped within one month and 6 had long-term
      success with a median period of 11 months (7-17 months). The latter were all
      previously subjected to breast conserving surgery and received qualified
      lactation counselling at delivery. The main reasons for not initiating
      breastfeeding were "uncertainty regarding maternal safety" and "a priori
      unfeasibility" expressed either by the obstetrician or by the oncologist. At a
      median follow-up of 48 months following delivery, all 20 women were alive with
      two relapses; one in each group (i.e., lactating and non-lactating). This
      analysis adds to the limited available evidence on the feasibility and safety of
      breastfeeding in breast cancer survivors. Proper fertility and survivorship
      counselling is crucial and requires more attention in breast cancer clinics.

PMID- 21078491
TI  - Stem cell ping-pong: the politics of science.

PMID- 21078492
TI  - Autoantibodies as markers for detecting concurrent disease activity in systemic
      lupus erythematosus.

PMID- 21078490
TI  - Italian consensus guidelines for chronic pancreatitis.
AB  - This paper gives practical guidelines for diagnosis and treatment of chronic
      pancreatitis. Statements have been elaborated by working teams of experts, by
      searching for and analysing the literature, and submitted to a consensus process
      by using a Delphi modified procedure. The statements report recommendations on
      clinical and nutritional approach, assessment of pancreatic function, treatment
      of exocrine pancreatic failure and of secondary diabetes, treatment of pain and
      prevention of painful relapses. Moreover, the role of endoscopy in approaching
      pancreatic pain, pancreatic stones, duct narrowing and dilation, and
      complications was considered. Recommendations for most appropriate use of various
      imaging techniques and of ultrasound endoscopy are reported. Finally, a group of
      recommendations are addressed to the surgical treatment, with definition of right
      indications, timing, most appropriate procedures and techniques in different
      clinical conditions and targets, and clinical and functional outcomes following
      surgery.

PMID- 21078493
TI  - Performance of anti-C1q, antinucleosome, and anti-dsDNA antibodies for detecting
      concurrent disease activity of systemic lupus erythematosus.
AB  - The objective of this study is to evaluate the specificity and sensitivity of
      antinucleosome, anti-C1q, and anti-dsDNA antibodies for detecting concurrent
      disease activity in systemic lupus erythematosus (SLE). Consecutive patients were
      recruited for serological testing of anti-dsDNA, IgG-antinucleosome, IgG-anti
      C1q, and complement levels. SLE disease activity was assessed by SLEDAI and
      physician's global assessment (PGA). The levels of these antibodies, complements,
      and disease activity scores were correlated. The specificity and sensitivity of
      these antibodies in detecting SLE activity was determined. We recruited 245 SLE
      patients (95% women, age 40.6 +/- 12.2 years). The prevalence of positive anti
      dsDNA, antinucleosome and anti-C1q antibodies was 55%, 44%, and 21%,
      respectively. All 3 antibodies correlated significantly with SLEDAI and PGA
      scores but were correlated inversely with complement levels (P < 0.001 in all).
      Titers of anti-dsDNA and anti-C1q, but not antinucleosome, correlated
      significantly with the renal SLEDAI score. The sensitivity of anti-dsDNA,
      antinucleosome, and anti-C1q for detecting the presence of active renal disease
      was 75%, 47%, and 53%, respectively. Anti-C1q had the highest specificity for
      active lupus renal disease (84%) followed by antinucleosome (57%) and the anti
      dsDNA antibody (49%). The negative predictive value (NPV) of a negative anti
      dsDNA and anti-C1q for active renal disease was 91%. For concurrent extrarenal
      SLE activity, the specificity was also highest with anti-C1q (83%). We conclude
      that antinucleosome does not perform better than anti-dsDNA for detecting
      concurrent SLE activity. The anti-C1q antibody, however, is more specific than
      anti-dsDNA for both active renal and extrarenal lupus. The absence of both anti
      dsDNA and anti-C1q has a high NPV for renal activity.

PMID- 21078494
TI  - Nicotine suppresses inflammatory factors in HBE16 airway epithelial cells after
      exposure to cigarette smoke extract and lipopolysaccharide.
AB  - Cigarette smoke is a major cause of chronic inflammatory pulmonary disease,
      leading to inflammation, mucin (MUC) production, tissue damage, and remodeling.
      It is also well known that the major addictive component of cigarette smoke is
      nicotine. This study focused on the role of nicotine in the development of
      inflammatory pulmonary disease induced by cigarette smoke. HBE16 human airway
      epithelial cells were treated with serial dilutions of cigarette smoke chloroform
      extract (CE), lipopolysaccharide (LPS), and nicotine. The release of MUC5AC,
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-6 protein were
      assayed by enzyme-linked immunosorbent assay. The MUC5AC protein also was
      observed by immunofluorescence. The expression of MUC5AC, TNF-alpha, IL-8, and IL
      6 mRNA were detected by real-time polymerase chain reaction. We found that the
      mRNA of the proinflammatory mediators TNF-alpha, IL-8, and IL-6, as well as
      MUC5AC was highly expressed after CE and LPS stimulation. Nicotine did not cause
      an excessive expression of TNF-alpha, IL-8, and IL-6, nor did it affect protein
      production from the MUC5AC gene. Nicotine not only failed to stimulate production
      of TNF-alpha, IL-8, and IL-6, but its presence was shown to suppress the
      activation resulting from exposure to CE and LPS (P < 0.05). Preincubation with
      nicotine also would reduce the level of MUC5AC protein in culture supernatants of
      CE- and LPS-treated cells. However, mRNA expression of MUC5AC showed no
      significant change in nicotine-treated cells when compared with normal control
      cells. This distinctive pattern implies that nicotine may have potential to
      suppress airway inflammation and maintain the mucus over retention in airway
      secretory cells to some extent, thus forming a balance between mucus
      hyperproduction and hypersecretion in airways exposed to smoking and LPS.

PMID- 21078496
TI  - Effects of long-term zinc treatment in Japanese patients with Wilson disease:
      efficacy, stability, and copper metabolism.
AB  - Wilson disease is an autosomal recessive disorder with copper metabolism. In
      Japan, the standard treatment is the administration of copper chelating agents,
      such as D-penicillamine and trientine. In this study, the authors used zinc
      acetate to treat Japanese patients with Wilson disease and investigated its
      efficacy. The 37 patients that comprise this study were found to have Wilson
      disease using clinical and biochemical tests and were administrated zinc acetate
      for 48 weeks. The authors followed the clinical symptoms and laboratory findings
      of the patients by assessing their complete blood counts, biochemical findings,
      as well as the results of urinalysis and special laboratory tests for copper and
      zinc metabolism. We also examined side effects of the treatment. Zinc acetate did
      not aggravate the hepatic or neurological symptoms of any of the patients. Blood
      biochemical analysis also did not reveal elevation of alanine aminotransferase,
      aspartate aminotransferase, and gamma-glutamyltranspeptidase levels. Zinc
      treatment did not aggravate the patients' clinical signs and/or laboratory
      findings. However, it did improve some clinical symptoms of the Wilson disease
      patients. Although this agent had some side effects, none of them were severe.
      The authors measured spot urinary copper excretion, which gave an indication of
      the efficacy of treatment and of the sufficient dosage of zinc. We recommend
      maintaining a spot urinary copper excretion less than 0.075-MUg/mg creatinine.
      The authors conclude that zinc acetate is an effective and safe treatment for
      Japanese patients with Wilson disease.

PMID- 21078495
TI  - Simvastatin inhibits goblet cell hyperplasia and lung arginase in a mouse model
      of allergic asthma: a novel treatment for airway remodeling?
AB  - Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung
      function, and persistent symptoms. Current therapies do not adequately treat the
      structural airway changes associated with asthma. The statins are cholesterol
      lowering drugs that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase,
      which is the rate-limiting step of cholesterol biosynthesis in the mevalonate
      (MA) pathway. These drugs have been associated with improved respiratory health,
      and ongoing clinical trials are testing their therapeutic potential in asthma. We
      hypothesized that simvastatin treatment of ovalbumin (OVA)-exposed mice would
      attenuate early features of airway remodeling by a mevalonate-dependent
      mechanism. BALB/c mice initially were sensitized to OVA and then exposed to 1%
      OVA aerosol for 2 weeks after sensitization for 6 exposures. Simvastatin (40
      mg/kg) or simvastatin plus MA (20 mg/kg) were injected intraperitoneally before
      each OVA exposure. Treatment with simvastatin attenuated goblet cell hyperplasia,
      arginase-1 protein expression, and total arginase enzyme activity, but it did not
      alter airway hydroxyproline content or transforming growth factor-beta1.
      Inhibition of goblet cell hyperplasia by simvastatin was mevalonate-dependent. No
      appreciable changes to airway smooth muscle cells were observed in any control or
      treatment groups. In conclusion, in an acute mouse model of allergic asthma,
      simvastatin inhibited early hallmarks of airway remodeling, which are indicators
      that can lead to airway thickening and fibrosis. Statins are potentially novel
      treatments for airway remodeling in asthma. Additional studies using subchronic
      or chronic allergen exposure models are needed to extend these initial findings.

PMID- 21078497
TI  - Culture of omentum-induced regenerating liver yielded hepatocyte-committed stem
      cells.
AB  - Earlier we showed that when omentum, activated by inert particles, is allowed to
      fuse to a wedge cut in the liver, it induces stem cell proliferation in the liver
      resulting in massive liver regeneration. Here, we attempt to culture stem cells
      from the omentum-induced regenerating liver tissue. Cells from regenerating liver
      tissue were harvested and cultured. Cultured cells were characterized by immune
      staining, fluorescence activated cell sorting analysis, growth factor assay, in
      vitro differentiation, and their ability to engraft to injured sites in vivo.
      Culture yielded cells with a mesenchymal stem cell phenotype that could be
      maintained in culture indefinitely. These cells, called regenerating liver stem
      cells, expressed both adult and embryonic stem cell markers, secreted high levels
      of vascular endothelial growth factor, and expressed albumin. When grown on
      matrigel in the presence of hepatocyte growth factor, these cells differentiated
      into hepatocyte-like cells in culture, but they did not differentiate to
      adipogenic and osteogenic lineages when grown in specific differentiation medium.
      The differentiated cells expressed alpha-fetoprotein and secreted high levels of
      albumin and urea. After systemic injection, the undifferentiated cells engrafted
      only to the injured sites in the liver and not to the normal areas of the liver.
      In conclusion, omentum-induced regenerating liver yields hepatocyte-committed
      stem cells in culture. Such cells could prove to be useful in cell
      transplantation therapies.

PMID- 21078499
TI  - What is your life's work?

PMID- 21078501
TI  - Answering the question, "what is a clinical nurse leader?": transition experience
      of four direct-entry master's students.
AB  - Understanding the experience of students learning the clinical nurse leader (CNL)
      role can be useful for faculty, preceptors, staff nurses, and interdisciplinary
      team members who guide them. This article analyzes the experience of four direct
      entry master's students in the first cohort to complete the CNL curriculum and to
      sit for the pilot CNL certification examination. Using action research
      methodology, the students worked with the clinical immersion practicum faculty
      and a writing consultant to develop the study purpose, collect and analyze data,
      and prepare a manuscript. The main theme that emerged was, answering the
      question, "what is a CNL?" Subthemes supporting the main theme involved coming to
      the edge, trusting the process, rounding the corner, and valuing becoming. The
      analysis confirmed the value the CNL offers as a new vision to nursing education
      and practice. The students offered suggestions for the CNL curriculum and
      practicum.

PMID- 21078500
TI  - An optimist's guide for cultivating civility among academic nurses.
AB  - Nurse educators yearn to teach in zestful workplaces where faculty and
      administrators work and play well together. Even when their interactions with
      professional colleagues are stressful, many still believe that zestful academic
      workplaces are possible. How can educators bridge the gap when a zestful ideal
      becomes a stressful reality? Since some report that the quality of their
      professional relationships differentiates stressful from zestful workplaces,
      relationships are a good place to start. The findings from an emerging body of
      social and biological research concur that human beings are a nurturing species
      wired for relationship. Interpersonal neurobiologists are finding that relational
      tending and mending are every much a part of the human response to stress as
      fight or flight. Given scientific support for the transformative power of
      connected relationships, this article poses and seeks to answer a single
      question. What if nurse educators, instead of fighting or fleeing when under
      stress, tended to and mended their professional relationships?

PMID- 21078502
TI  - The effect of context on nursing student math aptitude.
AB  - Math proficiency is a prerequisite to the performance of many nursing functions,
      including medication calculations, but many nursing students have difficulty
      performing this basic clinical skill. Research has demonstrated that math
      aptitude alone does not fully explain student outcomes on medication calculation
      assessments (MCAs), and contextual factors associated with reading and
      interpreting written medication questions are important for nurse educators to
      better understand. Reading and English aptitude are proposed as two potential
      contextual factors that may help explain the nursing student's ability to pass a
      written MCA. The purpose of this study was to describe the effects of reading and
      English aptitude on baccalaureate nursing students' ability to pass an MCA taken
      during the junior year of the nursing curriculum.

PMID- 21078503
TI  - Worth 1,000 words: concept mapping for tenure and promotion.
AB  - Organizing tenure/promotion dossiers can be a daunting task for junior faculty.
      As an adjunct to a strong program of scholarship, concept mapping can help as a
      concise and effective tool when applying for tenure and promotion. Concept
      mapping is explained here as a value-added, graphic method for junior faculty to
      use in presenting their scholarship accomplishments in the tenure and promotion
      dossier in a single overview beyond the written narrative. Further, skills in
      developing concept maps can be used as a mentoring technique, simultaneously
      helping faculty shape their scholarship as they progress toward tenure. The
      historically situated picture presented by a concept map is worth a thousand
      words.

PMID- 21078504
TI  - The lived experience of part-time baccalaureate nursing faculty.
AB  - Hiring part-time nursing faculty may impact students, faculty careers, and the
      institution. Yet, little has been studied, particularly in nursing, regarding the
      experiences of these faculty. This hermeneutic phenomenological study seeks to
      understand the lived experience of being a part-time faculty member in a
      baccalaureate nursing program. Through purposive and snowball sampling, nine
      nursing faculty in part-time positions in northeastern baccalaureate nursing
      programs participated in in-depth personal interviews. Four themes were uncovered
      during data analysis, including achieving the dream, a group divided, for the
      love of the students, and jump in and figure it out. Results of the study seem to
      indicate that the experience of being a part-time faculty differs in several ways
      from being a full-time faculty. Understanding part-time faculty experiences
      provides insight into faculty needs, issues, and concerns while facilitating the
      development of research-based recruitment and retention strategies.
      Recommendations for those involved in nursing education, including nursing
      faculty and administrators, are provided.

PMID- 21078505
TI  - The comprehensive examination: a viable master's of science in nursing capstone
      course.
AB  - The purpose of this article was to describe the process of how The University of
      Toledo College of Nursing developed the comprehensive examination as one capstone
      option to fulfill the requirements of a master's of science in nursing degree.
      Based on Keating's frame factors model, a review of existing literature, and an
      informal review of master's programs in nursing in the geographic area, an
      assessment was made of the viability of offering a comprehensive examination as a
      capstone experience. Increased student enrollment, need for flexible courses,
      faculty and student demographics, and institutional and national accreditation
      requirements were some of the factors that led to the decision to develop a
      comprehensive examination as a capstone option. The comprehensive examination has
      proven to be an educationally sound capstone option that was different from the
      traditional thesis or scholarly project. Benefits of the comprehensive
      examination have included increased faculty collegiality in writing and reading
      questions and answers, student satisfaction as evidenced by their evaluative
      written and verbal comments, and improved utilization of faculty related to
      workload and overall resources.

PMID- 21078506
TI  - Meeting the nursing faculty shortage challenge: an accelerated doctoral program
      in nursing.
AB  - In 2003, the Gordon and Betty Moore Foundation partnered with a major west coast
      school of nursing to create an accelerated doctoral program in nursing. The
      program's chief aim was to address the nursing shortage by increasing the number
      of nurse faculty by funding 42 doctoral students in five cohorts. Students
      accepted into the accelerated program receive a generous stipend and commit to
      earn their doctorate in 3 years and teach for 3 years after graduation at 1 of 17
      area nursing programs. Two cohorts have graduated from the accelerated program
      and are currently in faculty positions. This article describes the accelerated
      doctoral program and the academic progression and postgraduation employment of
      the first two cohorts.

PMID- 21078507
TI  - Technology in nursing education: a study of PDA use by students.
AB  - Personal digital assistants (PDAs) were first used by the public in the early
      1990 s. Initially used as a device to manage personal information, these devices
      quickly evolved. Currently, PDAs are capable of storing and exchanging large
      amounts of information, which truly make them handheld computers. As such, they
      have great value for professional use. Health care professionals require access
      to ever-expanding knowledge, and PDAs or other handheld computer devices can
      serve as valuable tools for education, information storage and retrieval, and
      clinical practice. This article describes the use of PDAs by undergraduate and
      graduate nursing students during their educational process. A descriptive study
      was conducted at a small, private university school of nursing at which all
      nursing students receive PDAs prior to their first clinical experiences. Findings
      from the study indicated that students used their PDAs for both classroom and
      clinical activities and that drug reference software was the most frequently used
      software application. Information was also obtained about the facilitators and
      barriers to PDA use.

PMID- 21078508
TI  - What lies beneath? The underlying principles structuring the field of academic
      nursing in Ireland.
AB  - This article reports the findings of a structural analysis of the field of
      academic nursing in Ireland and considers the implications of the field's current
      structure for its present status and future trajectory in the academy. Six years
      after preregistration nursing education transferred to the higher education
      sector, tensions continue to exist concerning the status and legitimacy of
      academic nursing and of those who profess to profess it. The languages of
      legitimation of senior nursing academics and national nursing leaders (n = 16)
      were elicited and subjected to a critical discourse analysis. Respondents'
      languages were analyzed in terms of the settings of four underlying structuring
      legitimation principles: autonomy, density, specialization, and temporality.
      Academic nursing in Ireland was found to be structured by low autonomy, high
      density, and weak specialization. I conclude that academic and professional
      leaders in Irish nursing need to urgently consider how academic nursing can
      reconfigure its relationships with clinical nursing, increase its intellectual
      autonomy, enhance its internal coherence and cohesiveness, strengthen the
      epistemic power of its knowledge base, and critically evaluate the ways in which
      past practices inform its present and whether and to what extent they should
      shape its future.

PMID- 21078509
TI  - Cognitive control in number processing: evidence from the unit-decade
      compatibility effect.
AB  - In this study we evaluated whether the reverse compatibility effect observed when
      participants compare two-digit Spanish number words might be modulated as a
      function of the percentage of filler trials (within-decade comparisons). The
      participants performed a comparison task with two-digit Spanish number words
      while the unit-decade compatibility in between decade comparison trials was
      manipulated. We biased the relevance of units by increasing the intra/inter
      decade comparison ratio (20%, 50%, and 70%). The compatibility effect shifted
      from reverse to regular depending on the unit relevance which indicates that the
      relative emphasis on the unit processing in two-digit number word can be
      modulated by the stimulus list. These results are discussed in terms of cognitive
      control in number processing.

PMID- 21078510
TI  - Synthesis and structure of 2-pyransoylperimidines.
AB  - The first examples of 2-pyranosylperimidines are reported. The beta-d
      glucopyranosyl nitrile oxide 5, generated by base-induced dehydrochlorination of
      the hydroximoyl chloride 4, reacted with 1,8-diaminonaphthalene to afford the 2
      (beta-d-glucopyranosyl)perimidine 8. The d-xylo-, d-galacto-, d-manno- and d
      glycero analogues 12, 15, 16 and 19 were prepared similarly. The glycals 9 and 13
      were formed as by-products resulting from elimination of acetic acid from the
      corresponding pyranosylperimidines. The structure of d-glucose-derived perimidine
      8 was established by X-ray crystallography.

PMID- 21078511
TI  - Maternal and newborn health in Tanzania.

PMID- 21078512
TI  - The dual influences of age and obstetric history on fecal continence in parous
      women.
AB  - OBJECTIVE: To assess whether women who underwent forceps delivery were more
      likely than those who delivered either normally (spontaneous vaginal delivery
      [SVD]) or by cesarean to experience deterioration in fecal continence as they
      aged. METHODS: The study investigated fecal continence assessment among women who
      gave birth to their first child 10, 20, or 30 years previously. Women who had
      undergone forceps delivery in the selected years were matched with women who had
      SVD in the same year. Two additional cohorts (1 premenopausal, 1 postmenopausal),
      who had only ever delivered by pre-labor cesarean, were identified for
      comparison. RESULTS: Of the 85 women who participated, 36 had undergone forceps
      delivery, 35 SVD, and 14 cesarean delivery only. The mode of vaginal delivery had
      no significant effect on continence scores or manometry pressures. Premenopausal
      women who had undergone cesarean delivery had significantly higher manometry
      pressures than those who delivered vaginally, but this protective effect was lost
      after the menopause. Multivariate analysis of pudendal nerve conduction found
      that the adverse effect of duration since delivery was greater than the adverse
      effect of forceps compared with vaginal delivery. CONCLUSION: Mode of delivery
      and aging affect pelvic floor function. Women who deliver via cesarean are not
      immune to age-related deterioration of anal sphincter function.

PMID- 21078514
TI  - A surfactant type fluorescence probe for detecting micellar growth.
AB  - We report on the detection of micellar growth in anionic, cationic, and
      catanionic surfactant systems using a novel surfactant type fluorescence probe,
      sodium 12-(N-dansyl)amino-dodecanate (12-DAN-ADA). The fluorescent group was
      incorporated in the tail of the surfactant which tethers the fluorescent group
      deep inside the apolar micellar cores. The fluorescence anisotropy of 12-DAN-ADA
      was found to be very sensitive for directly detecting the micellar growth in
      micelles containing oppositely charged surfactants, including cationic CTAB
      systems and mixed systems of oppositely charged surfactants (DEAB/SDS); in regard
      to the like charged SDS micellar systems, the sensitivity can be greatly enhanced
      by addition of a water soluble quencher which quenches the background
      fluorescence from the equilibrium population of free 12-DAN-ADA.

PMID- 21078515
TI  - Preparation of semiconductor-enriched single-walled carbon nanotube dispersion
      using a neutral pH water soluble chitosan derivative.
AB  - Debundling and selective dispersion of semiconducting single-walled carbon
      nanotubes (SWNTs) has been demonstrated using a neutral pH water soluble chitosan
      derivative, N-acetylated chitosan (NACHI), which is synthesized by controlled N
      acetylation of chitosan using acetic anhydride. The SWNT-NACHI supernatant
      solution demonstrated semiconductor-enriched property owing to the preferential
      adsorption of N-groups of the NACHI on semiconducting nanotubes with a fairly
      weak charge transfer. The dispersion of nearly individualized SWNTs achieved by
      surface modification of nanotubes with a biocompatible polymer can be utilized
      for electronic and biomedical applications such as field effect transistor,
      biosensor, cell culture medium and SWNT-biomacromolecule hybrid materials.

PMID- 21078516
TI  - Acute endovascular recanalization therapy in wake-up stroke.
AB  - BACKGROUND AND PURPOSE: Up to 15-25% of patients with ischemic stroke wake up
      with their deficits. Because of the uncertainty about the time of onset, these
      patients are generally not offered thrombolytic therapy. Some of these wake-up
      stroke patients may be eligible for acute endovascular stroke therapy based on
      hyperacute CT or MR imaging independent of the time window. REPORT: We report two
      patients with acute ischemic stroke whose symptoms were present upon awakening
      and who were successfully treated with endovascular interventions. RESULTS: The
      first patient was discharged with complete neurological recovery on second day
      after endovascular intervention. The second patient went home on fifth day with a
      mild left facial paresis and left arm drift. Both these patients did not have any
      neurological deficit on 18-month follow up. CONCLUSIONS: Some patients who
      present with stroke on awakening may be candidates for thrombolytic therapy or
      recanalization techniques irrespective of mode of therapy (intravenous,
      intravenous+intra-arterial or intra-arterial tPA alone). Further randomized,
      controlled studies are warranted to safely identify those candidates who would
      benefit from thrombolysis and endovascular interventions in ischemic wake-up
      strokes.

PMID- 21078517
TI  - Sunlight and MS.

PMID- 21078519
TI  - Synthesis, antitumor activity and QSAR studies of some 4-aminomethylidene
      derivatives of edaravone.
AB  - A series of aminomethylidene derivatives obtained from 4-formyledaravone were
      synthesized and characterized by IR, NMR and elemental analysis. All the
      compounds were screened for their antitumor activity. The compound containing 5
      phenylpyrazole moiety (3q) exhibited remarkable antitumor activity in in vitro
      assays, especially against human breast cancer MDA-MB-361 and MDA-MB-453 cell
      lines. The most important whole-molecule descriptors for antitumor activity on
      MDA-MB-453 cells belong to the group of quantum-chemical descriptors.

PMID- 21078520
TI  - Measurement of surface mercury fluxes at active industrial gold mines in Nevada
      (USA).
AB  - Mercury (Hg) may be naturally associated with the rock units hosting precious and
      base metal deposits. Active gold mines are known to have point source releases of
      Hg associated with ore processing facilities. The nonpoint source release of Hg
      to the air from the large area (hundreds to thousands of hectares) of disturbed
      and processed material at industrial open pit gold mines has not been quantified.
      This paper describes the field data collected as part of a project focused on
      estimating nonpoint source emissions of Hg from two active mines in Nevada, USA.
      In situ Hg flux data were collected on diel and seasonal time steps using a
      dynamic flux chamber from representative mine surfaces. Hg fluxes ranged from
      <1500 ng m(-2) day(-1) for waste rock piles (0.6-3.5 MUg g(-1)) to 684,000 ng m(
      2) day(-1) for tailings (2.8-58 MUg g(-1)). Releases were positively correlated
      with material Hg concentrations, surface grain size, and moisture content.
      Highest Hg releases occurred from materials under active cyanide leaching and
      from tailings impoundments containing processed high-grade ore. Data collected
      indicate that as mine sites are reclaimed and material disturbance ceases,
      emissions will decline. Additionally local cycling of atmospheric Hg (deposition
      and re-emission) was found to occur.

PMID- 21078521
TI  - Health risk assessment of personal inhalation exposure to volatile organic
      compounds in Tianjin, China.
AB  - Volatile Organic Compounds (VOCs) exposure can induce a range of adverse human
      health effects. To date, however, personal VOCs exposure and residential indoor
      and outdoor VOCs levels have not been well characterized in the mainland of
      China, less is known about health risk of personal exposure to VOCs. In this
      study, personal exposures for 12 participants as well as residential
      indoor/outdoor, workplace and in vehicle VOCs concentrations were measured
      simultaneously in Tianjin, China. All VOCs samples were collected using passive
      samplers for 5 days and were analyzed using Thermal Desorption GC-MS method. U.S.
      Environmental Protect Agency's Inhalation Unit Risks were used to calculate the
      inhalation cancer health risk. To assess uncertainty of health risk estimate,
      Monte Carlo simulation and sensitivity analysis were implemented. Personal
      exposures were greater than residential indoor exposures as expected with the
      exception of carbon tetrachloride. Exposure assessment showed modeled and
      measured concentrations are statistically linearly correlated for all VOCs
      (P<0.01) except chloroform, confirming that estimated personal exposure using
      time-weighted model can provide reasonable estimate of personal inhalation
      exposure to VOCs. Indoor smoking and recent renovation were identified as two
      major factors influencing personal exposure based on the time-activity pattern
      and factor analysis. According to the cancer risk analysis of personal exposure,
      benzene, chloroform, carbon tetrachloride and 1,3-butadiene had median upper
      bound lifetime cancer risks that exceeded the U.S. EPA benchmark of 1 per one
      million, and benzene presented the highest median risks at about 22 per one
      million population. The median cumulative cancer risk of personal exposure to 5
      VOCs was approximately 44 per million, followed by indoor exposure (37 per
      million) and in vehicle exposure (36 per million). Sensitivity analysis suggested
      that improving the accuracy of exposure measurement in further research would
      advance the health risk assessment.

PMID- 21078523
TI  - Anxiety measures validated in perinatal populations: a systematic review.
AB  - BACKGROUND: Research and screening of anxiety in the perinatal period is hampered
      by a lack of psychometric data on self-report anxiety measures used in perinatal
      populations. This paper aimed to review self-report measures that have been
      validated with perinatal women. METHODS: A systematic search was carried out of
      four electronic databases. Additional papers were obtained through searching
      identified articles. Thirty studies were identified that reported validation of
      an anxiety measure with perinatal women. RESULTS: Most commonly validated self
      report measures were the General Health Questionnaire (GHQ), State-Trait Anxiety
      Inventory (STAI), and Hospital Anxiety and Depression Scales (HADS). Of the 30
      studies included, 11 used a clinical interview to provide criterion validity.
      Remaining studies reported one or more other forms of validity (factorial,
      discriminant, concurrent and predictive) or reliability. The STAI shows
      criterion, discriminant and predictive validity and may be most useful for
      research purposes as a specific measure of anxiety. The Kessler 10 (K-10) may be
      the best short screening measure due to its ability to differentiate anxiety
      disorders. The Depression Anxiety Stress Scales 21 (DASS-21) measures multiple
      types of distress, shows appropriate content, and remains to be validated against
      clinical interview in perinatal populations. LIMITATIONS: Nineteen studies did
      not report sensitivity or specificity data. The early stages of research into
      perinatal anxiety, the multitude of measures in use, and methodological
      differences restrict comparison of measures across studies. CONCLUSION: There is
      a need for further validation of self-report measures of anxiety in the perinatal
      period to enable accurate screening and detection of anxiety symptoms and
      disorders.

PMID- 21078522
TI  - Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial
      cancer risk.
AB  - OBJECTIVE: The insulin-like growth factor (IGF) pathway plays a critical role in
      the growth and development of the uterus and is believed to function as a
      mediator of steroid hormone actions in the endometrium. The local expression of
      genes encoding IGFs and IGF-binding proteins (IGFBPs) is important in determining
      IGF bioactivity in the uterus. Genetic variation in key genes within the IGF
      pathway may influence the rate of cellular proliferation and differentiation in
      the uterus and ultimately affect the risk of endometrial cancer. Our hypothesis
      is that variant alleles in key genes involved in the IGF pathway will influence
      the development of endometrial cancer. METHODS: We conducted a case-control study
      nested within the Nurses' Health Study (NHS) and the Women's Health Study (WHS)
      to investigate the association between forty-four polymorphisms within IGFI,
      IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive
      endometrial cancer cases and 1723 matched controls. We used conditional logistic
      regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to
      assess the risk of endometrial cancer. RESULTS: We observed an inverse
      association with IGFII rs3741211 and endometrial cancer risk (OR=0.79 (95% CI:
      0.63, 0.99)) and IGFII rs1004446 and endometrial cancer risk (OR=0.80 (95% CI:
      0.68, 0.94)). We also observed an inverse association with IGFBP-3 rs2453839 and
      endometrial cancer risk (OR=0.81 (95%CI: 0.67, 0.98). However, we did not observe
      any statistically significant associations with the polymorphisms in IGFI and
      IGFBP1 and endometrial cancer risk. CONCLUSIONS: Genetic variation with IGFII and
      IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in
      IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further
      research is needed.

PMID- 21078524
TI  - Diagnostic features of the cycloid psychoses in a first psychotic episode sample.
AB  - INTRODUCTION: The cycloid psychoses have not been included in the modern
      classifications-what makes scientific research difficult. The aim of the present
      study is to investigate the presence and specific characteristics of the cycloid
      psychoses in a broad sample of first psychotic episodes. METHODS: Seventy
      patients diagnosed with one-year first schizophrenia episode, schizophreniform
      disorder, or schizoaffective disorder were studied (mean age, 27.9 years old;
      SD+/-6.34). The detection of the possible cases of cycloid psychosis was done
      according to the Perris and Brockington operational criteria. Two groups of
      "cycloid" (n=11) and "non cycloid" (n=59) patients were compared according to
      demographic and clinical variables, and possible diagnostic variables were
      evaluated by the ROC curves. RESULTS: Significant differences were found between
      cycloid and non cycloid groups for a number of clinical variables: prodromic
      symptoms (p<0.001), PANSS total score (p=0.003), PANSS-P (p=0.009), PANSS-GP
      (p=0.001), total score for mania by EVMAC (p=0.001), and CDSS for depression
      (p=0.004). ROC curves were significant for PANSS-GP (AUC=0.791, p=0.002), EVMAC
      (AUC=0.938, p=0.001), and CDSS (AUC=0.770, p=0.005). A sensitivity/specificity
      study demonstrated a negative predictive value for PANSS-GP (93.88%), EVMAC
      (96.30%), and CDSS (93.88%). CONCLUSIONS: According to these results, cycloid
      psychoses might represent differentiated and well-defined clinical entity.

PMID- 21078525
TI  - The relationship between physical conditions and suicidal behavior among those
      with mood disorders.
AB  - BACKGROUND: There has recently been increased interest in the relationship
      between physical illness, mental illness, and suicide. The present study utilizes
      a large community-based sample to investigate the association between certain
      physical conditions and suicidal behavior, among those with a history of a mood
      disorder. METHODS: Data came from the nationally representative German Health
      Survey (N=4181, age 18-65). Physical conditions were assessed by a general
      practice physician. DSM-IV mental disorders were assessed using a modified
      version of the Composite International Diagnostic Interview. Among those with a
      lifetime mood disorders, suicidal ideation, plans, and attempts were assessed by
      self-report. Multiple logistic regression analyses were used to examine the
      association between physical conditions and suicidal behavior among those with a
      history of mood disorder. RESULTS: Anxiety and substance use disorders were
      significantly positively associated with suicidal behavior [OR 1.61, 95% CI 1.13
      2.31 and 2.01, 95% 1.34-3.00, respectively]. After adjusting for anxiety and
      substance use disorders as well as sociodemographic variables, respiratory
      illness, hypertension, and number of physical disorders were significantly
      associated with suicidal behavior [AORs 1.72, 1.68, and 1.16, respectively].
      LIMITATIONS: The findings of this study are limited to adults with a history of a
      mood disorder. Personality disorders were not assessed. CONCLUSION: The present
      study suggests that among people with mood disorder, respiratory illnesses,
      hypertension, and number of physical conditions are associated with suicidal
      behavior independent of the effects of comorbid mental illness. Clinicians should
      recognize the contributing risk of physical health problems to suicidal behavior.

PMID- 21078526
TI  - In-hospital worsening renal function is an independent predictor of one-year
      mortality in patients with acute myocardial infarction.
AB  - BACKGROUND: We investigated the incidence, clinical predictors and prognostic
      value of worsening renal function (WRF) regarding 1-year mortality in patients
      with acute myocardial infarction (AMI). METHODS: We collected in-hospital data
      from 447 patients hospitalized for AMI in our institute within 12h of symptoms'
      onset. WRF was defined as a 25% or more decrease in estimated glomerural
      filtration rate during hospital stay. From blood samples obtained on admission
      and throughout hospitalization hemoglobin, white blood cell count, C-reactive
      protein, B-type natriuretic peptide, plasma glucose, troponin I and baseline and
      peak creatinine levels were measured. Ejection fraction was calculated on
      admission with 2D echocardiography. All patients underwent coronary arteriography
      and the revascularization status (complete or not) was also recorded. The end
      point was all-cause mortality after one-year of follow-up. RESULTS: WRF was
      detected in 63 pts (16.7%) and age, ejection fraction and white blood cell count
      emerged as the only independent predictors. The incidence of 1-year mortality was
      10.7% (48 deaths). Patients with WRF exhibited higher 1-year mortality (37.5% vs.
      6.3%, log rank p<0.001) and were characterized by more severe and less completely
      treated coronary artery disease, greater degree of myocardial necrosis and marked
      neurohormonal activation. By applying multivariate Cox regression analysis WRF, B
      type natriuretic peptide, ejection fraction and admission diastolic blood
      pressure were identified as the only independent predictors of death.
      CONCLUSIONS: WRF is associated with adverse 1-year outcome in patients with AMI.
      Close monitoring of renal function in the acute phase of MI may substantially
      contribute to long-term risk stratification.

PMID- 21078527
TI  - Immune responses after acute ischemic stroke or myocardial infarction.
AB  - BACKGROUND: We recently demonstrated an immediate immunodepressive state after
      acute ischemic stroke in humans. METHODS: In the present study, we prospectively
      analyzed immune responses in patients with middle cerebral artery stroke (n=20),
      acute myocardial infarction (n=20) and healthy controls (n=20, also matched for
      age and gender). RESULTS: Compared to controls, a rapid depression of monocytic
      HLA-DR expression and a defective lymphocytic IFN-gamma production was obvious
      after ischemic stroke or myocardial infarction, while total counts of leukocytes
      and monocytes were significantly higher after myocardial infarction. A T cell
      mediated lymphopenia was accentuated in patients with severe stroke, obviously
      predisposing these patients for nosocomial infections. CONCLUSIONS: Our data
      reveal an immediate and to some extent differential suppression of cell-mediated
      immune responses after ischemic stroke or myocardial infarction respectively.

PMID- 21078528
TI  - Association between aortic calcification and stable obstructive coronary artery
      disease.
AB  - BACKGROUND: Coronary artery calcification (CAC) is correlated with aortic
      calcification (AC) and predicts coronary atherosclerosis as well as obstructive
      coronary artery disease (OCAD). This study aims to investigate whether AC
      predicts OCAD independent of CAC and its incremental value in predicting OCAD
      with CAC. METHODS: Among the consecutive patients who underwent 64-slice
      multidetector CT (MDCT), we enrolled 120 stable OCAD (luminal narrowing >= 50%)
      patients and 120 controls without OCAD, matched for cardiovascular risk factors.
      CAC, thoracic AC, and OCAD were determined by MDCT. RESULTS: The prevalence of AC
      and CAC were significantly higher in OCAD patients than in controls (64% vs. 48%,
      p = 0.019; 57% vs. 32%, p < 0.001, respectively). There is a significant
      correlation between AC and CAC scores in the overall study population (r = 0.528,
      p < 0.001). In univariate analysis, the odds ratios (ORs) of AC and CAC in
      predicting OCAD were 1.91 (95% CI, 1.14-3.21) and 2.82 (95% CI, 1.67-4.78),
      respectively. When an adjustment was made for each other, AC did not maintain a
      significant association with OCAD, whereas CAC persisted the association (OR,
      2.52; 95% CI, 1.42-4.47). Both AC and CAC present as compared to both absent was
      found to be a more potent predictor for OCAD (OR, 3.37; 95% CI 1.78-6.36, p <
      0.001) than CAC alone. CONCLUSIONS: The presence of AC was associated with stable
      OCAD independently from cardiovascular risk factors, but the association seemed
      to be based on the close correlation between AC and CAC. However, AC might have
      an incremental value with CAC for predicting OCAD.

PMID- 21078529
TI  - Long-term outcome after treatment of isolated pulmonary valve stenosis.
AB  - BACKGROUND: Few data are available on very long-term follow-up after treatment
      for isolated pulmonary valve stenosis (PVS), either surgically or by percutaneous
      balloon angioplasty (PBA). METHODS AND RESULTS: All patients with isolated PVS
      were selected from our database of congenital heart defects. Their records were
      reviewed systematically. We identified 79 surgically treated patients with a
      median follow-up of 22.5 years (range 0-45 years) and 139 PBA patients with
      median follow-up of 6.0 years (range 0-21 years). Echocardiographic and
      catheterization parameters indicate excellent results of both techniques in
      relieving the transpulmonary gradient. However, after initial surgery 20.3% of
      patients needed a cardiac re-intervention: 81% for severe pulmonary valve
      regurgitation, but none for residual pulmonary stenosis. After initial PBA a
      cardiac re-intervention was needed in 9.4% of patients. In 85% the indication was
      residual pulmonary stenosis, in none of them pulmonary regurgitation, although
      almost all patients developed a mild pulmonary regurgitation. Freedom of re
      intervention after surgery was 98.4%, 93.5%, 87.7%, 70.9% and 55.7% at 5, 10, 20,
      30 and 40 years postoperatively. Freedom of re-intervention in the PBA group was
      95.1%, 87.5% and 84.4% at 5, 10 and 20 years post-procedure. CONCLUSIONS: Both
      surgery and PBA are safe and successful in relieving the acute transpulmonary
      gradient. Long-term results of surgery are worse than previously thought due to
      severe PR. After PBA re-interventions for residual stenosis are frequently needed
      and the incidence of mild PR is high. Very long-term results of PBA are still
      unknown.

PMID- 21078530
TI  - Safety and intestinal microbiota modulation by the exopolysaccharide-producing
      strains Bifidobacterium animalis IPLA R1 and Bifidobacterium longum IPLA E44
      orally administered to Wistar rats.
AB  - Bifidobacterium animalis subsp. lactis IPLA R1 and Bifidobacterium longum IPLA
      E44 strains were tested for their safety and ability to modulate the intestinal
      microbiota in vivo. Chemically simulated gastrointestinal digestion showed
      considerably lower survival of E44 than R1 strain, the first microorganism also
      being more sensitive to refrigerated storage in 10% skimmed milk at 4 degrees C.
      Harmful glycosidic activities were absent, or at low levels, in the strains R1
      and E44. Both strains were sensitive to most antibiotics and resistant to
      aminoglycosides, a common feature in bifidobacteria. Similar to several other
      bifidobacteria strains, B. animalis subsp. lactis IPLA R1 displayed a moderate
      resistance against tetracycline which correlated with the presence of tet(W) gene
      in its genome. The general parameters indicating well-being status, as well as
      translocation to different organs and histological examination of the gut
      tissues, revealed no changes induced by the administration of bifidobacteria to
      rats. Twelve-week-old male Wistar rats were distributed into three groups, eight
      rats in each. Two groups were administered daily over 108cfu of the corresponding
      strain suspended in 10% skimmed milk for 24 days, whereas rats in the placebo
      group received skimmed milk without microorganisms added. The microbiota and
      short chain fatty acids (SCFA) were monitored in faeces at different time points
      during treatment and in caecum content at the end of the assay. Quantitative PCR
      (qPCR) showed that faecal and caecal Bifidobacterium levels were higher in
      bifidobacteria-fed rats than in the placebo rats at the end of the intervention,
      whereas total anaerobic plate counts did not show significant differences.
      Quantification of B. animalis and B. longum by qPCR showed that, independent of
      the microorganism administered, treatment with bifidobacteria resulted in higher
      levels of B. animalis in the caecum. PCR-DGGE analysis of microbial populations
      revealed a higher diversity of bands in caecum content of rats fed B. animalis
      IPLA R1 than in the placebo group and rats fed B. longum IPLA E44. Remarkably,
      although no variations in the proportion of acetate, propionate and butyrate were
      found, at the end of the assay the total SCFA concentration in the faeces of rats
      fed bifidobacteria was significantly higher and those in caecum content
      significantly lower, than that of the placebo group. This suggests a displacement
      of the SCFA production to parts of the colon beyond the caecum in rats receiving
      bifidobacteria. Therefore, the oral administration of B. animalis IPLA R1 and B.
      longum E44 can be considered safe, these microorganisms having the ability to
      modulate the intestinal microbiota of rats by influencing SCFA and the
      bifidobacterial population levels.

PMID- 21078531
TI  - The occurrence of virulence traits among high-level aminoglycosides resistant
      Enterococcus isolates obtained from feces of humans, animals, and birds in South
      Korea.
AB  - Enterococcus isolates (1500) obtained from the feces of 48 humans, 209
      domesticated food animals, and 155 wild geese in South Korea were characterized
      with respect to species status by PCR analyses and resistance to antibiotics. Of
      the 1500 strains examined, the majority (n=577) were Enterococcus faecalis from
      224 (54.4%) of the samples feces, while 299 were of E. faecium from 125 of the
      samples (30.3%), 224 were E. hirae from 101 (24.5%) of the samples, 94 were E.
      casseliflavus from 43 (10.4%) of the samples, and one was E. gallinarum. While
      305 isolated from 125 (30.3%) of the samples were unidentified species.
      Approximately 15, 60, 50, 55, 3, and 40% of samples obtained from beef cattle,
      chickens, ducks, swine, wild geese, and humans, respectively, yielded
      Enterococcus isolates that were resistant to high-levels of aminoglycosides
      (i.e., of gentamicin, kanamycin, and streptomycin, minimum inhibitory
      concentrations were >1000 mg/l). The 180 Enterococcus isolates that showed high
      levels of resistance to aminoglycoside antibiotics (HLAR) were screened for
      virulence genes encoding for aggregation substance (agg), cytolysin activator
      (cylA), gelatinase (gelE) and surface protein (esp). Of those, the gelE gene was
      found most frequently in chickens and ducks of the HLAR isolates, while 56 E.
      faecalis and 13 E. faecium HLAR were gelatinase positive and showed hemolysin
      activity. Multiple antibiotic resistant Enterococcus isolates carrying virulence
      genes were most frequently isolated from poultry and swine, and were mostly E.
      faecalis or E. faecium. These findings suggest that restriction of the use of
      antibiotics in food animal operations in South Korea, especially those involved
      in poultry and swine production would be desirable.

PMID- 21078532
TI  - Microbial inactivation and shelf life comparison of 'cold' hurdle processing with
      pulsed electric fields and microfiltration, and conventional thermal
      pasteurisation in skim milk.
AB  - Thermal pasteurisation (TP) is the established food technology for commercial
      processing of milk. However, degradation of valuable nutrients in milk and its
      sensory characteristics occurs during TP due to substantial heat exposure. Pulsed
      electric fields (PEF) and microfiltration (MF) both represent emerging food
      processing technologies allowing gentle milk preservation at lower temperatures
      and shorter treatment times for similar, or better, microbial inactivation and
      shelf stability when applied in a hurdle approach compared to TP. Incubated raw
      milk was used as an inoculum for the enrichment of skim milk with native
      microorganisms before PEF, MF, and TP processing. Inoculated milk was PEF
      processed at electric field strengths between 16 and 42 kV/cm for treatment times
      from 612 to 2105 MUs; accounting for energy densities between 407 and 815 kJ/L,
      while MF was applied with a transmembrane flux of 660 L/h m2. Milk was TP-treated
      at 75 degrees C for 24 s. Comparing PEF, MF, and TP for the reduction of the
      native microbial load in milk led to a 4.6 log10 CFU/mL reduction in count for
      TP, which was similar to 3.7 log10 CFU/mL obtained by MF (P>=0.05), and more
      effective than the 2.5 log10 CFU/mL inactivation achieved by PEF inactivation (at
      815 kJ/L (P<0.05)). Combined processing with MF followed by PEF (MF/PEF) produced
      a 4.1 (at 407 and 632 kJ/L), 4.4 (at 668 kJ/L) and 4.8 (at 815 kJ/L) log10 CFU/mL
      reduction in count of the milk microorganisms, which was comparable to that of TP
      (P>=0.05). Reversed processing (PEF/MF) achieved comparable reductions of 4.9,
      5.3 and 5.7 log10 CFU/mL (at 407, 632 and 668 kJ/L, respectively (P>=0.05)) and a
      higher inactivation of 7.1 log10 (at 815 kJ/mL (P<0.05)) in milk than for TP.
      Microbial shelf life of PEF/MF-treated (815 kJ/L) and TP-treated milk stored at 4
      degrees C was analysed over 35 days for total aerobic; enterobacteria; yeasts and
      moulds; lactobacilli; psychrotroph; thermoduric psychrotroph, mesophilic, and
      thermophilic; and staphylococci counts. For both PEF/MF and TP-treated milk an
      overall shelf stability of 7 days was observed based on total aerobic counts
      (P>=0.05). Milk hurdle processing with PEF/MF at its most effective treatment
      parameters produced greater microbial inactivation and overall similar shelf
      stability at lower processing temperatures compared to TP. With higher field
      strength, shorter treatment time, larger energy density, and rising temperature
      the efficacy of PEF/MF increased contrary to MF/PEF. Thus, PEF/MF represents a
      potential alternative for 'cold' pasteurisation of milk with improved quality.

PMID- 21078533
TI  - Inactivation behavior of Pseudomonas aeruginosa by supercritical N2O compared to
      supercritical CO2.
AB  - Interest is growing for a non-thermal sterilization technique in the food and
      pharmaceutical industries in order to ensure microbiological safety without the
      deterioration of product quality. In this study, supercritical nitrous oxide (SC
      N2O) treatment was carried out in a multi-batch system to examine its
      bactericidal effect and characteristics, which largely remains unclear. The
      effect of operating pressure, temperature, mixing intensity, and working volume
      ratio (defined as the ratio of sample volume to the reactor volume to be filled
      with SC fluids) on the inactivation efficiency of SC N2O were investigated in
      comparison with supercritical carbon dioxide (SC CO2) treatment. Pseudomonas
      aeruginosa was chosen as a model microorganism. A 8-log reduction of P.
      aeruginosa cell concentration (10% working volume) in neutral phosphate-buffered
      saline was achieved by the SC N2O treatment accompanying no pH change in the
      presence of vigorous mixing (600 rpm) within 6 min, in a condition of 37 degrees
      C and 10 MPa and its overall efficiency is comparable to the SC CO2 treatment.
      Among the reaction parameters investigated in this study, mixing intensity
      appeared to be the most important operating parameter affecting the bactericidal
      efficiency. The release of intracellular substances in cells as a result of the
      SC N2O treatment was explained as one of major bactericidal actions by the SC N2O
      treatment. At the same time, relatively negligible change of proteins or enzyme
      activities in the cells in case of the SC N2O treatment was observed compared to
      the SC CO2 treatment. Also, the observation by scanning and transmission electron
      microscopy shows the milder morphological change of SC N2O-treated cells in
      comparison with the SC CO2-treated cells. This study suggests that the SC N2O
      bactericidal application on food products would be a viable option over SC CO2
      application, when mild change of enzyme activity and the proteins, or no pH
      change are desired.

PMID- 21078534
TI  - Nurses' willingness to take care of people living with human immunodeficiency
      virus/acquired immunodeficiency syndrome (HIV/AIDS)--does a teaching intervention
      make a difference?
AB  - The aim of this study is to describe the impact of an education intervention
      programme on nurses' willingness to care for HIV-positive people in Lithuania.
      METHODS: The study utilizes a randomized controlled trial design (RCT). The total
      sample comprises 185 nurses working in medical, surgical and gynaecological
      units, and primary health care centres from the same hospital areas in three
      Lithuanian hospitals. The data were analyzed using SPSS 12.0 and descriptive
      statistics. FINDINGS: Our educational intervention did not have an impact on the
      nurses' willingness to take care of people living with HIV (PLHIV), as their
      level of willingness was high already before the education intervention.
      CONCLUSIONS: Further research on this issue is needed to try to understand the
      forces acting on our nursing staff in order to ensure appropriate care for PLHIV.

PMID- 21078535
TI  - An interactive web-based learning unit to facilitate and improve intrapartum
      nursing care of nursing students.
AB  - First clinical exposures are stressful situations for nursing students,
      especially, when practicing on the labour ward. The purpose of this study was to
      develop intrapartum nursing care web-based learning to facilitate students'
      acquisition of conceptual knowledge and performance skills. This web-based
      learning unit integrated the 5E-model and information technology with the lecture
      content. Eighty four nursing students were recruited in the study. The control
      group received traditional teaching, while the experimental group was
      supplemented with the web-based learning unit on intrapartum nursing care. The
      results showed that the students in the experimental group had significant higher
      scores in conceptual knowledge and performance skill. The students also had
      significant lower scores in ignorance - related stress when compared to those of
      the control group. The students supplemented with the web-based course showed a
      strong positive attitude toward the new learning method.

PMID- 21078536
TI  - Understanding and enhancing the learning experiences of culturally and
      linguistically diverse nursing students in an Australian bachelor of nursing
      program.
AB  - The growth in numbers of culturally and linguistically diverse students entering
      nursing programs in Australia presents challenges for academic and clinical
      staff, and most importantly the students themselves. In this paper we present the
      findings from a pilot study designed to explore these issues and to develop
      strategies to address them. This study used a qualitative explorative approach to
      gain rich in-depth data. Eleven culturally and linguistically diverse students,
      three clinical facilitators, and four academic staff participated in focus group
      interviews. Four major themes emerged: level of English language competence,
      feelings of isolation, limited opportunities for learning, and inadequate
      university support. The issues we identified led to a meaningful discussion of
      the political, financial, social and intercultural context that they are
      entrapped in. This paper provides educators, clinicians, policy makers and
      researchers with an insight where and how they commence to break the trap and
      highlights, the need for further research into the perspectives of Australian
      students' who study and socialise with their international peers.

PMID- 21078537
TI  - Independent prognostic variables in acute myeloid leukaemia.
AB  - Acute myeloid leukaemia (AML) is one of the most common haematological
      malignancies and is increasing in frequency due to an ageing population. Whilst
      remission will be achieved in up to 80% of those receiving intensive
      chemotherapy, the main variables precluding cure are the treatment-related
      mortality and relapse rates. Decisions on intensification, de-escalation and
      allografting rely on the ability to divide an apparently homogeneous group
      according to risk. A wide range of clinical, cytogenetic and molecular variables
      may be used to inform this task. Cytogenetic and molecular characterisation has
      already identified subgroups, such as acute promyelocytic leukaemia (APL) with
      t(15;17)/PML-RARA and AML with FLT3 mutation for which targeted therapies are
      available, and further molecularly defined groups who may be potential candidates
      for this approach are likely to be identified in the future. This review examines
      the range of established clinical and diagnostic parameters that should be used
      in assessing prognosis for a patient with AML and looks ahead to an expanding
      repertoire of potential variables that are currently under evaluation.

PMID- 21078538
TI  - Use of spent substrate after Pleurotus pulmonarius cultivation for the treatment
      of chlorothalonil containing wastewater.
AB  - Lignocellulosic materials are used as substrate for the cultivation of the edible
      mushroom Pleurotus pulmonarius. After two or three flushes of mushrooms, the
      spent substrate is discarded although it still has an important enzymatic
      activity that can be used for several purposes. In this study, we sought to
      determine the technical feasibility of using spent substrate from P. pulmonarius
      to degrade chlorothalonil. Reaction mixture was prepared with 6 ml of pesticide
      aqueous solution (2 mg active ingredient/l) and 3 ml of enzymatic extract
      obtained from spent P. pulmonarius substrate. The enzymatic reaction (27  degrees
      C, pH 7.4) was conducted for 1 h with sampling at 15 min intervals. The effect of
      storage time and temperature (freezing or refrigerating) of spent substrate and
      enzymatic extract, respectively, on the activity over chlorothalonil was
      determined. Freshly obtained spent substrate extract was able to reduce 100% of
      the initial concentration of chlorothalonil (2 mg/l) after 45 min of reaction.
      Storage time had a negative effect on the stability of the enzymatic activity:
      with spent substrate stored for a week, chlorothalonil concentration was reduced
      in 49.5% after 1 h reaction and with substrate stored for two and three weeks,
      the degradation efficiency decreased to 9.15% and 0%, respectively. Cooling and
      freezing the spent substrate extract also had a negative effect on chlorothalonil
      degradation.

PMID- 21078539
TI  - Glucocorticoid receptor signaling and prostate cancer.
AB  - Glucocorticoids (GCs) are provided to hormone-refractory prostate cancer (HRPC)
      patients partly due to the inhibitory effects on adrenal androgen production
      acting as a pituitary suppressant. Nowadays, the combination of chemotherapy and
      dexamethasone is a standard treatment for HRPC patients while increasing evidence
      suggests that a lot of local tissue factors like growth factors,
      angiogenic/lymphogenic factors, apoptosis-related factors, cytokines related to
      the transition of prostate cancer from androgen dependence to hormone-refractory
      status, are among the targets of GR signaling. However, although glucocorticoids
      have been recognized to be one of a limited number of treatment options for HRPC,
      the molecular basis of GC-induced effects in prostate cancer remains poorly
      defined. In this review, we focus on how GCs induce effects via the GR-mediated
      transcriptional regulation of specific genes known to play key roles in
      cellular/tissue functions, including growth, apoptosis, inflammation, metastasis,
      differentiation, cell survival and angiogenesis. In our effort to unravel the
      molecular interplay of GR signaling with other signaling cascades prevalent in
      prostate cancer, we also include a detailed description of GR gene and protein
      structure/function and provide the knowledge gained recently into the
      mechanism(s) of the cross talk between GR and other signaling cascades via which
      GCs exert their multiple effects.

PMID- 21078540
TI  - Genistein potentiates the effect of arsenic trioxide against human hepatocellular
      carcinoma: role of Akt and nuclear factor-kappaB.
AB  - Hepatocellular carcinoma (HCC) is a highly lethal malignancy mostly because of de
      novo and acquired resistance to conventional chemotherapy. Constitutive
      activation of Akt and nuclear factor-kappaB (NF-kappaB) represent major cellular
      abnormalities associated with both the pathogenesis and therapeutic resistance of
      HCC. The aim of the present study was to determine whether genistein, a natural
      Akt/NF-kappaB inhibitor, could enhance the anti-HCC efficacy of ATO both in vitro
      and in vivo. Our results demonstrated that genistein not only potentiated the
      proliferation-inhibiting and apoptosis-inducing effect of ATO on human HCC cell
      lines in vitro, but also dramatically augmented its suppressive effect on both
      tumor growth and angiogenesis in nude mice. The mechanism is at least partially
      due to the suppressive effect of genistein both on the proper and ATO-induced Akt
      activation, and on the activity of NF-kappaB, and the latter correlated with the
      suppression of NF-kappaB regulated gene products, including cyclin D1, Bcl-xL,
      Bcl-2, c-myc, COX-2, and VEGF. These data suggest that the combination of ATO
      with genistein presents a promising therapeutic approach for the treatment of
      HCC.

PMID- 21078541
TI  - Fucoxanthin and its deacetylated product, fucoxanthinol, induce apoptosis of
      primary effusion lymphomas.
AB  - Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin's lymphoma caused
      by human herpesvirus 8. Conventional chemotherapy has limited effect on PEL, and
      the prognosis is poor. Carotenoids are a family of natural pigments and have
      several biological functions. We evaluated the anti-PEL effects of carotenoid,
      fucoxanthin (FX) and its metabolite, fucoxanthinol (FXOH). Treatment of PEL cells
      with FX or FXOH induced cell cycle arrest during G1 phase and caspase-dependent
      apoptosis. FX and FXOH treatment silenced NF-kappaB, AP-1 and Akt activation, in
      conjunction with down-regulation of anti-apoptotic proteins and cell cycle
      regulators. Importantly, proteasome degradation was responsible for the low
      levels of proteins after FXOH treatment. In animal studies, treatment with FX
      reduced the growth of PEL-cell tumors. The results provide the rationale for
      future clinical use of FX and FXOH for the treatment of PEL.

PMID- 21078542
TI  - Targeting heat shock proteins in cancer.
AB  - Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are powerful chaperones. Their
      expression is induced in response to a wide variety of physiological and
      environmental insults including anti-cancer chemotherapy, thus allowing the cell
      to survive to lethal conditions. Different functions of HSPs have been described
      to account for their cytoprotective function, including their role as molecular
      chaperones as they play a central role in the correct folding of misfolded
      proteins, but also their anti-apoptotic properties. HSPs are often overexpressed
      in cancer cells and this constitutive expression is necessary for cancer cells'
      survival. HSPs may have oncogene-like functions and likewise mediate "non
      oncogene addiction" of stressed tumor cells that must adapt to a hostile
      microenvironment, thereby becoming dependent for their survival on HSPs. HSP
      targeting drugs have therefore emerged as potential anti-cancer agents. This
      review describes the different molecules and approaches being used or proposed in
      cancer therapy based on the in inhibition of HSP90, HSP70 and HSP27.

PMID- 21078543
TI  - Trp-P-1, a carcinogenic heterocyclic amine, inhibits lipopolysaccharide-induced
      maturation and activation of human dendritic cells.
AB  - Carcinogens frequently provoke immunosuppressive effects thereby allowing cancer
      cells to persist in the host. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P
      1) is a carcinogenic heterocyclic amine that is abundantly produced by
      overcooking meat and fish. Here, we investigated the effect of Trp-P-1 on
      dendritic cells (DCs), which play a central role in the appropriate activation of
      the host immune system. When human monocyte-derived DCs were stimulated with
      lipopolysaccharide (LPS), the DCs became mature with an increase in the
      expression of co-stimulatory receptors such as CD80, CD86, and MHC molecules and
      a decrease in phagocytic capacity. Trp-P-1 inhibited all of these phenomena under
      the same conditions. In addition, Trp-P-1 inhibited production of the cytokines
      TNF-alpha and IL-12 in LPS-stimulated DCs. Furthermore, DCs that were pre-exposed
      to Trp-P-1 were less efficient in inducing activation and proliferation of
      autologous T cells than control DCs. Trp-P-1 also attenuated the ability of DCs
      to directly kill T-cell lymphoma Jurkat cells. Mechanism studies showed that Trp
      P-1 did not inhibit LPS-binding to Toll-like receptor 4 but interfered with the
      signaling pathways mediated through p38 kinase. In conclusion, our results
      suggest that Trp-P-1 is immunosuppressive by inhibiting the functionality of DCs
      that play an essential role in the appropriate induction of anti-cancer immune
      responses.

PMID- 21078545
TI  - Duloxetine in patients with central neuropathic pain caused by spinal cord injury
      or stroke: a randomized, double-blind, placebo-controlled trial.
AB  - The mechanisms underlying central neuropathic pain are poorly understood. Pain
      inhibitory mechanisms including sertononergic and norepinephrine systems may be
      dysfunctional. In this randomized, double-blinded, placebo-controlled trial we
      evaluated the effects of duloxetine on pain relief (spontaneous pain and evoked
      pain), tolerability, health status, and quality of life in patients with central
      pain related to cerebrovascular lesions or spinal cord lesions. At baseline and
      eight weeks following start of treatment subjects were evaluated with standard
      measures of efficacy: pain intensity (primary efficacy variable), quantitative
      sensory testing, health status and quality of life (secondary efficacy
      variables). Forty-eight patients received escalating doses of either duloxetine
      (60 and 120mg/day) or matching placebo capsules. In both groups, patients started
      with 1 capsule per day. If pain relief was insufficient, patients were titrated
      to a higher dose. A trend towards a decrease in mean pain score after eight weeks
      was observed for duloxetine treatment (p=0.056). Duloxetine alleviated dynamic
      (p=0.035) and cold allodynia (p<0.001) significantly better than placebo. Tactile
      pain and pressure pain thresholds did not improve significantly. The duloxetine
      group showed a significant improvement for the bodily pain domain of the SF36
      (p=0.035). No significant differences were observed in the other domains of the
      SF36, the Pain Disability Index, and the EQ-5D. While this trial showed no
      significant effect on pain intensity, duloxetine revealed a biologic effect. It
      would be worthwhile to suspend our judgement and to perform more studies to
      evaluate the role of duloxetine in modulation of the symptoms of central
      neuropathic pain.

PMID- 21078544
TI  - Targeting apoptosis pathways in pancreatic cancer.
AB  - Pancreatic cancer - here in particular pancreatic ductal adenocarcinoma (PDAC) -
      is still a highly therapy refractory disease. Amongst the mechanisms by which
      PDAC cells could escape any non-surgical therapy, anti-apoptotic protection seems
      to be the most relevant one. PDAC cells have acquired resistance to apoptotic
      stimuli such as death ligands (FasL, TRAIL) or anti-cancer drugs (gemcitabine) by
      a great number of molecular alterations either disrupting an apoptosis inducing
      signal or counteracting the execution of apoptosis. Thus, PDAC cells exhibit
      alterations in the EGFR/MAPK/Ras/raf1-, PI3K/Akt-, TRAIL/TRAF2-, or IKK/NF-kappaB
      pathway accompanied by deregulations in the expression of apoptosis regulators
      such as cIAP, Bcl2, XIAP or survivin. Along with protection against apoptosis,
      PDAC cells also overexpress histone deacetylases (HDACs) giving rise to
      epigenetic patterns of chemoresistance and to acetylation of other regulatory
      proteins, as well. With respect to the multitude of anti-apoptotic pathways, a
      great number of molecular targets might be of high potential in novel therapy
      strategies. Thus, natural compounds as well as novel synthetic drugs are
      considered to be used in single or combined therapy of PDAC. A number of
      proteasome and HDAC inhibitors or selective inhibitors of IKK, EGFR, Akt and mTOR
      have been widely explored in preclinical settings and clinical studies. Even
      though these early studies encouraged an application in a clinical setting, most
      of the trials have been rather disappointing yet. Thus, new molecular targets and
      novel concepts of combination therapies need to get access into clinical trials -
      either in neoadjuvant/adjuvant or in palliative treatments.

PMID- 21078546
TI  - Acupuncture analgesia: areas of consensus and controversy.

PMID- 21078547
TI  - Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and
      clinical response in advanced metastatic gastrointestinal stromal tumor (GIST):
      an emerging role for drug blood level testing?
AB  - Imatinib is the standard of care for patients with advanced metastatic
      gastrointestinal stromal tumors (GIST), and is also approved for adjuvant
      treatment in patients at substantial risk of relapse. Studies have shown that
      maximizing benefit from imatinib depends on long-term administration at
      recommended doses. Pharmacokinetic (PK) and pharmacodynamic factors, adherence,
      and drug-drug interactions can affect exposure to imatinib and impact clinical
      outcomes. This article reviews the relevance of these factors to imatinib's
      clinical activity and response in the context of what has been demonstrated in
      chronic myelogenous leukemia (CML), and in light of new data correlating imatinib
      exposure to response in patients with GIST. Because of the wide inter-patient
      variability in drug exposure with imatinib in both CML and GIST, blood level
      testing (BLT) may play a role in investigating instances of suboptimal response,
      unusually severe toxicities, drug-drug interactions, and suspected non-adherence.
      Published clinical data in CML and in GIST were considered, including data from a
      PK substudy of the B2222 trial correlating imatinib blood levels with clinical
      responses in patients with GIST. Imatinib trough plasma levels < 1100 ng/mL were
      associated with lower rates of objective response and faster development of
      progressive disease in patients with GIST. These findings have been supported by
      other analyses correlating free imatinib (unbound) levels with response. These
      results suggest a future application for imatinib BLT in predicting and
      optimizing therapeutic response. Nevertheless, early estimates of threshold
      imatinib blood levels must be confirmed prospectively in future studies and
      elaborated for different patient subgroups.

PMID- 21078548
TI  - Analysis of vitamin B1 in dry-cured sausages by hydrophilic interaction liquid
      chromatography (HILIC) and diode array detection.
AB  - A method based on hydrophilic interaction liquid chromatography (HILIC) and diode
      array detection (DAD) was developed to quantify thiamine (vitamin B1)
      concentration in Spanish dry-cured sausages ("chorizo," "fuet," and
      "salchichon"). Samples were extracted with diluted acid (HCl 0.1M) followed by an
      enzymatic hydrolysis to release vitamin B1 vitamers from food matrix. Crude
      extracts were purified on a weak cation exchange SPE cartridge and total thiamine
      concentration was determined by LC-HILIC-DAD with a limit of detection better
      than 0.01 mg/100g. The proposed conditions, that do not require the
      derivatization of the extracts nor the use of fluorescence or MS detectors, are
      suitable to provide chromatographic separation and identification of vitamin B1
      within 8 min. Selectivity, repeatability and accuracy of the method were
      evaluated with both spiked samples and the reference material Pig Liver BCR(r)
      487. Quantification of vitamin B1 was also carried out for different kinds of
      commercial samples of Spanish dry-cured products.

PMID- 21078549
TI  - Neurodevelopmental outcomes of very low birth weight and extremely low birth
      weight infants at 18 months of corrected age associated with prenatal risk
      factors.
AB  - BACKGROUND: Very premature infants occasionally have neurodevelopmental
      disabilities. However, there have been quite limited data on prenatal risk
      factors associated with their neurodevelopmental outcomes. AIM: To clarify the
      relationship between prenatal risk factors and neurodevelopmental outcomes of
      very premature infants. STUDY DESIGN: The study design is a retrospective review.
      SUBJECTS: One hundred seventy Japanese women with a singleton pregnancy and their
      infants whose birth weight being less than 1500 g were included. We classified
      those infants into 118 appropriate for gestational age (AGA) and 52 small for
      gestational age (SGA) infants. OUTCOME MEASURES: Infants' neurodevelopmental
      outcomes at 18 months of corrected age were evaluated by the Kyoto Scale of
      Psychological Development 2001 (KSPD). We analyzed and compared the infants'
      outcomes and prenatal risk factors between two groups. RESULTS: Mortality and
      rate of infants unevaluable by KSPD because of severe impairment were not
      significantly different between those groups. However, the developmental quotient
      score of the cognitive-adaptive area in SGA infants born between 25 and 31 weeks
      of gestation was significantly lower than that in AGA infants randomly selected
      as gestation-matched controls. More advanced gestational age and heavier birth
      weight protected against adverse neurodevelopmental outcomes in both groups.
      Moreover, male infants were related to the excess risk of adverse
      neurodevelopmental outcomes in the SGA group. CONCLUSION: In view of the
      neurodevelopment of the infants, it seems that the most efficient obstetric
      strategy for improving prognosis of premature infants should be targeted to
      prolong the pregnancy period as long as the reassuring fetal status and maternal
      stable health condition are being confirmed.

PMID- 21078550
TI  - A continuous process for biodiesel production in a fixed bed reactor packed with
      cation-exchange resin as heterogeneous catalyst.
AB  - Continuous esterification of free fatty acids (FFA) from acidified oil with
      methanol was carried out with NKC-9 cation-exchange resin in a fixed bed reactor
      with an internal diameter of 25 mm and a height of 450 mm to produce biodiesel.
      The results showed that the FFA conversion increased with increases in
      methanol/oil mass ratio, reaction temperature and catalyst bed height, whereas
      decreased with increases in initial water content in feedstock and feed flow
      rate. The FFA conversion kept over 98.0% during 500 h of continuous
      esterification processes under 2.8:1 methanol to oleic acid mass ratio, 44.0 cm
      catalyst bed height, 0.62 ml/min feed flow rate and 65 degrees C reaction
      temperature, showing a much high conversion and operational stability.
      Furthermore, the loss of sulfonic acid groups from NKC-9 resin into the
      production was not found during continuous esterification. In sum, NKC-9 resin
      shows the potential commercial applications to esterification of FFA.

PMID- 21078551
TI  - Performance of heterogeneous ZrO2 supported metaloxide catalysts for brown grease
      esterification and sulfur removal.
AB  - In order to achieve a viable biodiesel industry, new catalyst technology is
      needed which can process a variety of less expensive waste oils, such as yellow
      grease and brown grease. However, for these catalysts to be effective for
      biodiesel production using these feedstocks, they must be able to tolerate higher
      concentrations of free fatty acids (FFA), water, and sulfur. We have developed a
      class of zirconia supported metaloxide catalysts that achieve high FAME yields
      through esterification of FFAs while simultaneously performing desulfurization
      and de-metallization functions. In fact, methanolysis, with the zirconia
      supported catalysts, was more effective for desulfurization than an acid washing
      process. In addition, using zirconia supported catalysts to convert waste grease,
      high in sulfur content, resulted in a FAME product that could meet the in-use
      ASTM diesel fuel sulfur specification (<500 ppm). Possible mechanisms of
      desulfurization and de-metallization by methanolysis were proposed to explain
      this activity.

PMID- 21078552
TI  - Consuming un-captured methane from landfill using aged refuse bio-cover.
AB  - A novel simulated bio-cover was developed to facilitate the biological methane
      oxidation process using aged refuse and aged sludge from landfill. It was found
      that 78.7% and 66.9% of CH(4) could be removed, with the aged refuse: aged sludge
      (w/w%) ratio of 7:3 and 6:4 in bio-cover system, respectively. The maximum CH(4)
      removal rate could reach 100%, when the aged refuse with the disposal time more
      than 14 years were applied in bio-cover. Some controlled factors for the
      methanotrophic activity, i.e. moisture, Eh and organic matter content, were also
      investigated. It was found that CH(4) oxidation rate increased greatly, when the
      moisture content and organic matter were increased from 6.0%, 4.8% to 8.0%, 9.5%,
      respectively. The optimum conditions for this bio-cover system was found to be as
      follows: aged refuse: aged sludge ratio of 7:3, the moisture content of 8-9%, Eh
      of 104-108 mV and organic matter of 9.5%.

PMID- 21078553
TI  - Recycling of organic wastes by employing Eisenia fetida.
AB  - This paper reports the recycling of nutrients by vermicomposting of cow dung
      (CD), poultry droppings (PD) and food industry sludge (FIS) employing earthworms
      (Eisenia fetida). A total of six vermicomposting units were established and
      dynamics of chemical and biological parameters has been studied for 13 weeks. The
      waste mixture containing 50% CD+25% PD+25% FIS had better fertilizer value among
      studied waste combinations. At the end of experiment, vermicomposts showed
      decrease in pH and organic C, but increase in EC, total Kjeldhal N, total
      available P and total K contents. The C:N ratio of final vermicomposts also
      reduced to 10.7-12.7 from 22.8 to 56 in different waste combinations. The
      earthworms have good biomass gain and cocoon production in all vermicomposting
      units but CD alone and 50% CD+25% PD+25% FIS were better than other studied
      combinations.

PMID- 21078554
TI  - Protein kinase affinity reagents based on a 5-aminoindazole scaffold.
AB  - Affinity reagents that target protein kinases are powerful tools for signal
      transduction research. Here, we describe a general set of kinase ligands based on
      a 5-aminoindazole scaffold. This scaffold can readily be derivatized with diverse
      binding elements and immobilized analogs allow selective enrichment of protein
      kinases from complex mixtures.

PMID- 21078555
TI  - Discovery of a novel IKK-beta inhibitor by ligand-based virtual screening
      techniques.
AB  - Various inflammatory stimuli that activate the nuclear factor kappa B (NF-kappaB)
      signaling pathway converge on a serine/threonine kinase that displays a key role
      in the activation of NF-kappaB: the I kappa B kinase beta (IKK-beta). Therefore,
      IKK-beta is considered an interesting target for combating inflammation and
      cancer. In our study, we developed a ligand-based pharmacophore model for IKK
      beta inhibitors. This model was employed to virtually screen commercial
      databases, giving a focused hit list of candidates. Subsequently, we scored by
      molecular shape to rank and further prioritized virtual hits by three-dimensional
      shape-based alignment. One out of ten acquired and biologically tested compounds
      showed inhibitory activity in the low micromolar range on IKK-beta enzymatic
      activity in vitro and on NF-kappaB transactivation in intact cells. Compound 8 (2
      (1-adamantyl)ethyl 4-[(2,5-dihydroxyphenyl)methylamino]benzoate) represents a
      novel chemical class of IKK-beta inhibitors and shows that the presented model is
      a valid approach for identification and development of new IKK-beta ligands.

PMID- 21078556
TI  - Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine
      inhibitors of BACE-1.
AB  - Heterocyclic replacement of the isophthalamide phenyl ring in hydroxyethylamine
      (HEA) BACE-1 inhibitors was explored. A variety of indole-1,3-dicarboxamide HEAs
      exhibited potent BACE-1 enzyme inhibition, but displayed poor cellular activity.
      Improvements in cellular activity and aspartic protease selectivity were observed
      for 7-azaindole-1,3-dicarboxamide HEAs. A methylprolinol-bearing derivative (10n)
      demonstrated robust reductions in rat plasma Abeta levels, but did not lower rat
      brain Abeta due to poor central exposure. The same analog exhibited a high efflux
      ratio in a bidirectional Caco-2 assay and was likely a substrate of the efflux
      transporter P-glycoprotein. X-ray crystal structures are reported for two indole
      HEAs in complex with BACE-1.

PMID- 21078557
TI  - Structure based optimization of chromen-based TNF-alpha converting enzyme (TACE)
      inhibitors on S1' pocket and their quantitative structure-activity relationship
      (QSAR) study.
AB  - A series of coumarin based TACE inhibitors were designed to bind in S1' pocket of
      TACE enzyme based on their docking study. Twelve analogues were synthesized and
      most of compounds were active in vitro TACE enzyme inhibition as well as cellular
      TNF-alpha inhibition. Among these, 15l effectively inhibited the production of
      serum TNF-alpha by oral administration at a dose of 30 mg/kg. Compound 15l also
      showed a good oral bioavailability at 42% and effectively inhibited paw edema in
      rat carrageenan model. Quantitative structure-activity relationship (QSAR) study
      using genetic function approximation technique (GFA) and docking study were
      performed to confirm the series of coumarin core TACE inhibitors. QSAR model have
      been evaluated internally and externally using test set prediction. Through
      docking study of each molecule, it is validated that the electrostatic
      descriptors from the QSAR equation could explain the importance of S1' pocket and
      the TACE inhibitory activity well.

PMID- 21078558
TI  - Parametric study of the X-ray primary spectra obtained with the MTSVD unfolding
      method.
AB  - The modified truncated singular value decomposition (MTSVD) unfolding method is
      applied to obtain primary spectra for X-ray tubes in radiodiagnostic. Three
      parameters - voltage, anode angle and filter thickness - of the tube are tested.
      Unfolded spectra are compared with theoretical extracted from IPEM-78 catalogue.
      A 2sigma error criterion is applied to assess the minimum variations in tested
      parameters that permits distinguishing between close spectra.

PMID- 21078559
TI  - Assessing the optical changes in dissolved organic matter in humic lakes by
      spectral slope distributions.
AB  - The impact of photodegradation and mixing processes on the optical properties of
      dissolved organic matter (DOM) was examined using a distribution of absorption
      spectral slopes and fluorescence measurements in two Argentine lakes. By
      examining the variability of the absorption spectral slopes throughout the
      ultraviolet and visible wavelengths, it was possible to determine which
      wavelength intervals were most sensitive to dominant loss processes. For DOM
      photodegradation, results show that increases in the absorption spectral slope
      between 265 and 305 nm were highly sensitive to increased exposure to solar
      ultraviolet radiation. A slightly larger wavelength range (265-340 nm) was found
      to be influenced when both mixing and photodegradation processes were considered,
      in terms DOM residence time, DOM absorption and UV diffuse attenuation
      coefficients. This same interval of spectral slopes (265-340 nm) was found to
      highly correlate with changes in fluorescence emission/excitation in wavelengths
      that are typically associated with terrestrial humic-like DOM. The identification
      of specific wavelength intervals, rather than the use of standard wavelength
      intervals or ratios, improved our ability to identify the dominant dissolved
      organic matter (humic-like) and major loss mechanisms (photodegradation) in these
      lakes.

PMID- 21078561
TI  - Neuromuscular fatigue after maximal exercise in patients with cystic fibrosis.
AB  - The aim of this study was to determine whether patients with cystic fibrosis
      (CF), despite their ventilatory limitation, would develop neuromuscular fatigue
      of quadriceps muscles following a maximal cycling exercise. Eleven adults with CF
      (age=26.8+/-6.9years; forced expiratory volume in 1s=54.1+/-12.8% predicted) and
      11 age-matched healthy subjects performed a maximal incremental cycle test with
      respiratory gas exchange measurements. Maximal voluntary contraction (MVC) and
      electromyographic (EMG) activity of the vastus medialis muscle were recorded
      before and after exercise. Neural and contractile properties of the quadriceps
      were also investigated using femoral nerve electrical stimulation. Patients had
      lower exercise capacity, peak oxygen uptake and MVC than controls. MVC fell
      significantly postexercise in both groups (CF: -20+/-10%, controls: -19+/-6%;
      p<0.01). EMG root mean square values, M-wave amplitude and duration were
      unchanged in both groups. Peak twitch (-46.9+/-13.8%), maximal rate of twitch
      torque development (-50.3+/-13.8%) and relaxation (-35.2+/-19.5%) were all
      reduced after exercise in CF patients. The control group followed the same
      pattern (-38.4+/-14.4%, -42.1+/-14.7% and -15+/-20.4%) but the statistical
      significance was not reached for the maximal rate of twitch torque relaxation. In
      conclusion, CF patients demonstrated lower limb fatigue following symptom-limited
      cycle exercise, which was comparable to that exhibited by healthy controls. This
      fatigue may be due to contractile impairments and not to transmission failure.
      Further studies should be conducted in a larger sample to confirm these
      preliminary results.

PMID- 21078560
TI  - Facultative heterochromatin formation at the IL-1 beta promoter in LPS tolerance
      and sepsis.
AB  - The clinical phenotype in sepsis that is observed as LPS tolerance is determined
      by silencing of pro-inflammatory genes like IL-1 beta (IL-1beta). This study
      shows that facultative heterochromatin (fHC) silences IL-1beta expression during
      sepsis, where we find dephosphorylated histone H3 serine 10 and increased binding
      of heterochromatin protein-1 (HP-1) to the promoter. In both human sepsis blood
      leukocytes and an LPS tolerant human THP-1 cell model, we show that IkappaBalpha
      and v-rel reticuloendotheliosis viral oncogene homolog B (RelB) function as
      dominant labile mediators of fHC formation at the IL-1beta promoter. Protein
      synthesis inhibition decreases levels of IkappaBalpha and RelB, converts silent
      fHC to euchromatin, and restores IL-1beta transcription. We further show TLR
      dependent NFkappaB p65 and histone H3 serine 10 phosphorylation binding at the
      promoter. We conclude that the resolution phase of sepsis, which correlates with
      survival in humans, may depend on the plasticity of chromatin structure as found
      in fHC.

PMID- 21078563
TI  - Insulin resistance in obesity and metabolic syndrome: is there a connection with
      platelet l-arginine transport?
AB  - OBJECTIVE: Nitric oxide (NO) is a short-lived gaseous messenger with multiple
      physiological functions including regulation of blood flow, platelet adhesion and
      aggregation inhibition. NO synthases (NOS) catalyze the conversion of cationic
      amino acid L-arginine in L-citrulline and NO. Despite an increasing prevalence of
      obesity and metabolic syndrome (MetS) in the last decades, the exact mechanisms
      involved in the pathogenesis and cardiovascular complications are not fully
      understood. We have examined the effects of obesity and MetS on the L-arginine-NO
      cGMP pathway in platelets from a population of adolescents. MATERIALS: A total of
      twenty six adolescent patients (13 with obesity and 13 with MetS) and healthy
      volunteers (n=14) participated in this study. Transport of L-arginine, NO
      synthase (NOS) activity and cGMP content in platelets were analyzed. Moreover,
      platelet function, plasma levels of L-arginine, metabolic and clinical markers
      were investigated in these patients and controls. RESULTS: L-arginine transport
      (pmol/10(9) cells/min) in platelets via system y(+)L was diminished in obese
      subjects (20.8+/-4.7, n=10) and MetS patients (18.4+/-3.8, n=10) compared to
      controls (52.3+/-14.8, n=10). The y(+)L transport system correlated negatively to
      insulin levels and Homeostasis Model Assessment of Insulin Resistance (HOMA IR)
      index. No differences in NOS activity and cGMP content were found among the
      groups. Moreover, plasma levels of L-arginine were not affected by obesity or
      MetS. DISCUSSION: Our study provides the first evidence that obesity and MetS
      lead to a dysfunction of L-arginine influx, which negatively correlates to
      insulin resistance. These findings could be a premature marker of future
      cardiovascular complications during adulthood.

PMID- 21078564
TI  - Exploring the effects of pulsed ultrasound at 205 and 616 kHz on the sonochemical
      degradation of octylbenzene sulfonate.
AB  - Compared to continuous wave (CW) ultrasound, pulsed wave (PW) ultrasound has been
      shown to result in enhanced sonochemical degradation of octylbenzene sulfonate
      (OBS). However, pulsed ultrasound was investigated under limited pulsing
      conditions. In this study, pulse-enhanced degradation of OBS was investigated
      over a broad range of pulsing conditions and at two ultrasonic frequencies (616
      and 205 kHz). The rate of OBS degradation was compared to the rate of formation
      of 2-hydroxyterephthalic acid (HTA) following sonolysis of aqueous terephthalic
      acid (TA) solutions. This study shows that sonication mode and ultrasound
      frequency affect both OBS degradation and HTA formation rates, but not
      necessarily in the same way. Unlike TA, OBS, being a surface active solute,
      alters the cavitation bubble field by adsorbing to the gas/solution interface of
      cavitation bubbles. Enhanced OBS degradation rates during pulsing are attributed
      to this adsorption process. However, negative or smaller pulse enhancements
      compared to enhanced HTA formation rates are attributed to a decrease in the high
      energy stable bubble population and a corresponding increase in the transient
      bubble population. Therefore, sonochemical activity as determined from TA
      sonolysis cannot be used as a measure of the effect of pulsing on the rate of
      degradation of surfactants in water. Over relatively long sonolysis times, a
      decrease in the rate of OBS degradation was observed under CW, but not under PW
      conditions. We propose that the generation and accumulation of surface active and
      volatile byproducts on the surface and inside of cavitation bubbles,
      respectively, during CW sonolysis is a contributing factor to this effect. This
      result suggests that there are practical applications to the use of pulsed
      ultrasound as a method to degrade surface active contaminants in water.

PMID- 21078562
TI  - Specific and nonspecific thalamocortical functional connectivity in normal and
      vegetative states.
AB  - Recent theoretical advances describing consciousness from information and
      integration have highlighted the unique role of the thalamocortical system in
      leading to integrated information and thus, consciousness. Here, we examined the
      differential distributions of specific and nonspecific thalamocortical functional
      connections using resting-state fMRI in a group of healthy subjects and
      vegetative-state patients. We found that both thalamic systems were widely
      distributed, but they exhibited different patterns. Nonspecific connections were
      preferentially associated with brain regions involved in higher-order cognitive
      processing, self-awareness and introspective mentalizing (e.g., the dorsal
      prefrontal and anterior cingulate cortices). In contrast, specific connections
      were prevalent in the ventral and posterior part of the prefrontal and precuneus,
      known involved in representing externally-directed attentions. Significant
      reductions of functional connectivity in both systems, especially the nonspecific
      system, were observed in VS. These data suggest that brain networks sustaining
      information and integration may be differentiated by the nature of their thalamic
      functional connectivity.

PMID- 21078565
TI  - Hepatic vein stenosis (Budd-Chiari syndrome) as a cause of ascites in a cat.
AB  - A 10-year-old cat presented with a history of unexplained ascites. Ultrasound and
      angiography identified an isolated stenosis of the middle hepatic vein resulting
      in Budd-Chiari Syndrome. Balloon dilation of the stenosis was attempted but the
      patient expired. Necropsy revealed a discrete membranous stenosis at the junction
      of the caudal vena cava and the middle hepatic vein. The literature was reviewed
      to assess clinical and diagnostic findings, as well as therapeutic options in
      humans with hepatic vein stenosis.

PMID- 21078566
TI  - Random walks on graphs for salient object detection in images.
AB  - We formulate the problem of salient object detection in images as an automatic
      labeling problem on the vertices of a weighted graph. The seed (labeled) nodes
      are first detected using Markov random walks performed on two different graphs
      that represent the image. While the global properties of the image are computed
      from the random walk on a complete graph, the local properties are computed from
      a sparse k-regular graph. The most salient node is selected as the one which is
      globally most isolated but falls on a locally compact object. A few background
      nodes and salient nodes are further identified based upon the random walk based
      hitting time to the most salient node. The salient nodes and the background nodes
      will constitute the labeled nodes. A new graph representation of the image that
      represents the saliency between nodes more accurately, the "pop-out graph" model,
      is computed further based upon the knowledge of the labeled salient and
      background nodes. A semisupervised learning technique is used to determine the
      labels of the unlabeled nodes by optimizing a smoothness objective label function
      on the newly created "pop-out graph" model along with some weighted soft
      constraints on the labeled nodes.

PMID- 21078567
TI  - A blind watermarking scheme using new nontensor product wavelet filter banks.
AB  - As an effective method for copyright protection of digital products against
      illegal usage, watermarking in wavelet domain has recently received considerable
      attention due to the desirable multiresolution property of wavelet transform. In
      general, images can be represented with different resolutions by the wavelet
      decomposition, analogous to the human visual system (HVS). Usually, human eyes
      are insensitive to image singularities revealed by different high frequency
      subbands of wavelet decomposed images. Hence, adding watermarks into these
      singularities will improve the imperceptibility that is a desired property of a
      watermarking scheme. That is, the capability for revealing singularities of
      images plays a key role in designing wavelet-based watermarking algorithms.
      Unfortunately, the existing wavelets have a limited ability in revealing
      singularities in different directions. This motivates us to construct new wavelet
      filter banks that can reveal singularities in all directions. In this paper, we
      utilize special symmetric matrices to construct the new nontensor product wavelet
      filter banks, which can capture the singularities in all directions. Empirical
      studies will show their advantages of revealing singularities in comparison with
      the existing wavelets. Based upon these new wavelet filter banks, we, therefore,
      propose a modified significant difference watermarking algorithm. Experimental
      results show its promising results.

PMID- 21078568
TI  - Remote health monitoring of heart failure with data mining via CART method on HRV
      features.
AB  - Disease management programs, which use no advanced information and computer
      technology, are as effective as telemedicine but more efficient because less
      costly. We proposed a platform to enhance effectiveness and efficiency of home
      monitoring using data mining for early detection of any worsening in patient's
      condition. These worsenings could require more complex and expensive care if not
      recognized. In this letter, we briefly describe the remote health monitoring
      platform we designed and realized, which supports heart failure (HF) severity
      assessment offering functions of data mining based on the classification and
      regression tree method. The system developed achieved accuracy and a precision of
      96.39% and 100.00% in detecting HF and of 79.31% and 82.35% in distinguishing
      severe versus mild HF, respectively. These preliminary results were achieved on
      public databases of signals to improve their reproducibility. Clinical trials
      involving local patients are still running and will require longer
      experimentation.

PMID- 21078569
TI  - Subspace methods for identification of human ankle joint stiffness.
AB  - Joint stiffness, the dynamic relationship between the angular position of a joint
      and the torque acting about it, describes the dynamic, mechanical behavior of a
      joint during posture and movement. Joint stiffness arises from both intrinsic and
      reflex mechanisms, but the torques due to these mechanisms cannot be measured
      separately experimentally, since they appear and change together. Therefore, the
      direct estimation of the intrinsic and reflex stiffnesses is difficult. In this
      paper, we present a new, two-step procedure to estimate the intrinsic and reflex
      components of ankle stiffness. In the first step, a discrete-time, subspace-based
      method is used to estimate a state-space model for overall stiffness from the
      measured overall torque and then predict the intrinsic and reflex torques. In the
      second step, continuous-time models for the intrinsic and reflex stiffnesses are
      estimated from the predicted intrinsic and reflex torques. Simulations and
      experimental results demonstrate that the algorithm estimates the intrinsic and
      reflex stiffnesses accurately. The new subspace-based algorithm has three
      advantages over previous algorithms: 1) It does not require iteration, and
      therefore, will always converge to an optimal solution; 2) it provides better
      estimates for data with high noise or short sample lengths; and 3) it provides
      much more accurate results for data acquired under the closed-loop conditions,
      that prevail when subjects interact with compliant loads.

PMID- 21078570
TI  - Characterization of electrophotographic print artifacts: banding, jitter, and
      ghosting.
AB  - Electrophotographic (EP) print banding, jitter, and ghosting artifacts are common
      sources of print quality degradation. Traditionally, the characterization of
      banding and jitter artifacts relies mainly on the assumption that the defect has
      either a horizontal or vertical orientation which permits the simple 1-D analysis
      of the defect profile. However, this assumption can easily be violated if a small
      amount of printer or scanner skew is introduced to the analyzed images. In some
      cases, the defect can inherently be neither vertical nor horizontal. In this
      case, unless the defect orientation has been accurately detected before analysis,
      the 1-D-based approaches could bias the estimation of the defect severity. In
      this paper, we present an approach to characterize the jitter and banding
      artifacts of unrestricted orientation using wavelet filtering and 2-D spectral
      analysis. We also present a new system for detecting and quantifying ghosting
      defects. It includes a design for a printed test pattern to emphasize the
      ghosting defect and facilitate further processing and analysis. Wavelet filtering
      and a template matching technique are used to detect the ghost location along and
      across the scanned test pattern. A new metric is developed to quantify ghosting
      based upon its contrast, shape, and location consistency. Our experimental
      results show that the proposed approaches provide objective measures that
      quantify EP defects with a rank ordering correlation coefficient of 0.8 to 0.98,
      as compared to the subjective assessment of print quality experts.

PMID- 21078571
TI  - A generalized unsharp masking algorithm.
AB  - Enhancement of contrast and sharpness of an image is required in many
      applications. Unsharp masking is a classical tool for sharpness enhancement. We
      propose a generalized unsharp masking algorithm using the exploratory data model
      as a unified framework. The proposed algorithm is designed to address three
      issues: (1) simultaneously enhancing contrast and sharpness by means of
      individual treatment of the model component and the residual, (2) reducing the
      halo effect by means of an edge-preserving filter, and (3) solving the out-of
      range problem by means of log-ratio and tangent operations. We also present a
      study of the properties of the log-ratio operations and reveal a new connection
      between the Bregman divergence and the generalized linear systems. This
      connection not only provides a novel insight into the geometrical property of
      such systems, but also opens a new pathway for system development. We present a
      new system called the tangent system which is based upon a specific Bregman
      divergence. Experimental results, which are comparable to recently published
      results, show that the proposed algorithm is able to significantly improve the
      contrast and sharpness of an image. In the proposed algorithm, the user can
      adjust the two parameters controlling the contrast and sharpness to produce the
      desired results. This makes the proposed algorithm practically useful.

PMID- 21078572
TI  - Practical bounds on image denoising: from estimation to information.
AB  - Recently, in a previous work, we proposed a way to bound how well any given image
      can be denoised. The bound was computed directly from the noise-free image that
      was assumed to be available. In this work, we extend the formulation to the more
      practical case where no ground truth is available. We show that the parameters of
      the bounds, namely the cluster covariances and level of redundancy for patches in
      the image, can be estimated directly from the noise corrupted image. Further, we
      analyze the bounds formulation to show that these two parameters are
      interdependent and they, along with the bounds formulation as a whole, have a
      nice information-theoretic interpretation as well. The results are verified
      through a variety of well-motivated experiments.

PMID- 21078573
TI  - Balanced multiwavelets with interpolatory property.
AB  - Balanced multiwavelets with interpolatory property are discussed in this paper.
      This kind of multiwavelets can have a sampling property like Shannon's sampling
      theorem. It has been shown that the corresponding matrix-valued refinable mask
      has special structure, and an orthogonal multifilter bank {H(z),G(z)} can be
      reduced to a scalar valued conjugate quadrature filter (CQF) a(z) . But it does
      not mean that any scalar CQF can form a "good" multifilter bank which can
      generate a vector-valued refinable function with some degree of smoothness. In
      the context of balanced multiwavelets, we give the definition of transferring
      balance order, which a scalar CQF a(z) satisfies, to guarantee that the
      multiwavelet Psi generated is balanced. On the basis of the parametrization of a
      scalar CQF with any length and conditions of transferring balance order,
      parametrization of multifilter banks which can generate interpolatory
      multiwavelet and interpolatory scaling function, is gotten. Moreover, some
      balanced interpolatory multiwavelets have been constructed. Interpolatory
      analysis-ready multiwavelets (armlets) are also discussed in this paper. It is
      known that conditions of armlets are easy to validate, compared with balanced
      multiwavelets. But it will be present that if the corresponding scaling function
      Phi is interpolatory, the multiwavelet Psi is balanced of order n if and only if
      it is an armlet of order n. Finally, the application of balanced multiwavelets
      with interpolatory property in image processing is also discussed.

PMID- 21078574
TI  - A linear programming approach for optimal contrast-tone mapping.
AB  - This paper proposes a novel algorithmic approach of image enhancement via optimal
      contrast-tone mapping. In a fundamental departure from the current practice of
      histogram equalization for contrast enhancement, the proposed approach maximizes
      expected contrast gain subject to an upper limit on tone distortion and
      optionally to other constraints that suppress artifacts. The underlying contrast
      tone optimization problem can be solved efficiently by linear programming. This
      new constrained optimization approach for image enhancement is general, and the
      user can add and fine tune the constraints to achieve desired visual effects.
      Experimental results demonstrate clearly superior performance of the new approach
      over histogram equalization and its variants.

PMID- 21078575
TI  - High capacity color barcodes: per channel data encoding via orientation
      modulation in elliptical dot arrays.
AB  - We present a new high capacity color barcode. The barcode we propose uses the
      cyan, magenta, and yellow (C,M,Y) colorant separations available in color
      printers and enables high capacity by independently encoding data in each of
      these separations. In each colorant channel, payload data is conveyed by using a
      periodic array of elliptically shaped dots whose individual orientations are
      modulated to encode the data. The orientation based data encoding provides
      beneficial robustness against printer and scanner tone variations. The overall
      color barcode is obtained when these color separations are printed in overlay as
      is common in color printing. A reader recovers the barcode data from a
      conventional color scan of the barcode, using red, green, and blue (R,G,B)
      channels complementary, respectively, to the print C, M, and Y channels. For each
      channel, first the periodic arrangement of dots is exploited at the reader to
      enable synchronization by compensating for both global rotation/scaling in
      scanning and local distortion in printing. To overcome the color interference
      resulting from colorant absorptions in noncomplementary scanner channels, we
      propose a novel interference minimizing data encoding approach and a statistical
      channel model (at the reader) that captures the characteristics of the
      interference, enabling more accurate data recovery. We also employ an error
      correction methodology that effectively utilizes the channel model. The
      experimental results show that the proposed method works well, offering (error
      free) operational rates that are comparable to or better than the highest
      capacity barcodes known in the literature.

PMID- 21078576
TI  - High dynamic range image display with halo and clipping prevention.
AB  - The dynamic range of an image is defined as the ratio between the highest and the
      lowest luminance level. In a high dynamic range (HDR) image, this value exceeds
      the capabilities of conventional display devices; as a consequence, dedicated
      visualization techniques are required. In particular, it is possible to process
      an HDR image in order to reduce its dynamic range without producing a significant
      change in the visual sensation experienced by the observer. In this paper, we
      propose a dynamic range reduction algorithm that produces high-quality results
      with a low computational cost and a limited number of parameters. The algorithm
      belongs to the category of methods based upon the Retinex theory of vision and
      was specifically designed in order to prevent the formation of common artifacts,
      such as halos around the sharp edges and clipping of the highlights, that often
      affect methods of this kind. After a detailed analysis of the state of the art,
      we shall describe the method and compare the results and performance with those
      of two techniques recently proposed in the literature and one commercial
      software.

PMID- 21078577
TI  - Information content weighting for perceptual image quality assessment.
AB  - Many state-of-the-art perceptual image quality assessment (IQA) algorithms share
      a common two-stage structure: local quality/distortion measurement followed by
      pooling. While significant progress has been made in measuring local image
      quality/distortion, the pooling stage is often done in ad-hoc ways, lacking
      theoretical principles and reliable computational models. This paper aims to test
      the hypothesis that when viewing natural images, the optimal perceptual weights
      for pooling should be proportional to local information content, which can be
      estimated in units of bit using advanced statistical models of natural images.
      Our extensive studies based upon six publicly-available subject-rated image
      databases concluded with three useful findings. First, information content
      weighting leads to consistent improvement in the performance of IQA algorithms.
      Second, surprisingly, with information content weighting, even the widely
      criticized peak signal-to-noise-ratio can be converted to a competitive
      perceptual quality measure when compared with state-of-the-art algorithms. Third,
      the best overall performance is achieved by combining information content
      weighting with multiscale structural similarity measures.

PMID- 21078578
TI  - Geometrically induced force interaction for three-dimensional deformable models.
AB  - In this paper, we propose a novel 3-D deformable model that is based upon a
      geometrically induced external force field which can be conveniently generalized
      to arbitrary dimensions. This external force field is based upon hypothesized
      interactions between the relative geometries of the deformable model and the
      object boundary characterized by image gradient. The evolution of the deformable
      model is solved using the level set method so that topological changes are
      handled automatically. The relative geometrical configurations between the
      deformable model and the object boundaries contribute to a dynamic vector force
      field that changes accordingly as the deformable model evolves. The geometrically
      induced dynamic interaction force has been shown to greatly improve the
      deformable model performance in acquiring complex geometries and highly concave
      boundaries, and it gives the deformable model a high invariancy in initialization
      configurations. The voxel interactions across the whole image domain provide a
      global view of the object boundary representation, giving the external force a
      long attraction range. The bidirectionality of the external force field allows
      the new deformable model to deal with arbitrary cross-boundary initializations,
      and facilitates the handling of weak edges and broken boundaries. In addition, we
      show that by enhancing the geometrical interaction field with a nonlocal edge
      preserving algorithm, the new deformable model can effectively overcome image
      noise. We provide a comparative study on the segmentation of various geometries
      with different topologies from both synthetic and real images, and show that the
      proposed method achieves significant improvements against existing image gradient
      techniques.

PMID- 21078579
TI  - Nonlocal Mumford-Shah regularizers for color image restoration.
AB  - We propose here a class of restoration algorithms for color images, based upon
      the Mumford-Shah (MS) model and nonlocal image information. The Ambrosio
      Tortorelli and Shah elliptic approximations are defined to work in a small local
      neighborhood, which are sufficient to denoise smooth regions with sharp
      boundaries. However, texture is nonlocal in nature and requires semilocal/non
      local information for efficient image denoising and restoration. Inspired from
      recent works (nonlocal means of Buades, Coll, Morel, and nonlocal total variation
      of Gilboa, Osher), we extend the local Ambrosio-Tortorelli and Shah
      approximations to MS functional (MS) to novel nonlocal formulations, for better
      restoration of fine structures and texture. We present several applications of
      the proposed nonlocal MS regularizers in image processing such as color image
      denoising, color image deblurring in the presence of Gaussian or impulse noise,
      color image inpainting, color image super-resolution, and color filter array
      demosaicing. In all the applications, the proposed nonlocal regularizers produce
      superior results over the local ones, especially in image inpainting with large
      missing regions. We also prove several characterizations of minimizers based upon
      dual norm formulations.

PMID- 21078580
TI  - A filtering approach to edge preserving MAP estimation of images.
AB  - The authors present a computationally efficient technique for maximum a
      posteriori (MAP) estimation of images in the presence of both blur and noise. The
      image is divided into statistically independent regions. Each region is modelled
      with a WSS Gaussian prior. Classical Wiener filter theory is used to generate a
      set of convex sets in the solution space, with the solution to the MAP estimation
      problem lying at the intersection of these sets. The proposed algorithm uses an
      underlying segmentation of the image, and a means of determining the segmentation
      and refining it are described. The algorithm is suitable for a range of image
      restoration problems, as it provides a computationally efficient means to deal
      with the shortcomings of Wiener filtering without sacrificing the computational
      simplicity of the filtering approach. The algorithm is also of interest from a
      theoretical viewpoint as it provides a continuum of solutions between Wiener
      filtering and Inverse filtering depending upon the segmentation used. We do not
      attempt to show here that the proposed method is the best general approach to the
      image reconstruction problem. However, related work referenced herein shows
      excellent performance in the specific problem of demosaicing.

PMID- 21078581
TI  - GRISSOM platform: enabling distributed processing and management of biological
      data through fusion of grid and web technologies.
AB  - Transcriptomic technologies have a critical impact in the revolutionary changes
      that reshape biological research. Through the recruitment of novel high
      throughput instrumentation and advanced computational methodologies, an
      unprecedented wealth of quantitative data is produced. Microarray experiments are
      considered high-throughput, both in terms of data volumes (data intensive) and
      processing complexity (computationally intensive). In this paper, we present
      grids for in silico systems biology and medicine (GRISSOM), a web-based
      application that exploits GRID infrastructures for distributed data processing
      and management, of DNA microarrays (cDNA, Affymetrix, Illumina) through a
      generic, consistent, computational analysis framework. GRISSOM performs versatile
      annotation and integrative analysis tasks, through the use of third-party
      application programming interfaces, delivered as web services. In parallel, by
      conforming to service-oriented architectures, it can be encapsulated in other
      biomedical processing workflows, with the help of workflow enacting software,
      like Taverna Workbench, thus rendering access to its algorithms, transparent and
      generic. GRISSOM aims to set a generic paradigm of efficient metamining that
      promotes translational research in biomedicine, through the fusion of grid and
      semantic web computing technologies.

PMID- 21078582
TI  - Efficient decoding with steady-state Kalman filter in neural interface systems.
AB  - The Kalman filter is commonly used in neural interface systems to decode neural
      activity and estimate the desired movement kinematics. We analyze a low
      complexity Kalman filter implementation in which the filter gain is approximated
      by its steady-state form, computed offline before real-time decoding commences.
      We evaluate its performance using human motor cortical spike train data obtained
      from an intracortical recording array as part of an ongoing pilot clinical trial.
      We demonstrate that the standard Kalman filter gain converges to within 95% of
      the steady-state filter gain in 1.5+/-0.5 s (mean +/-s.d.). The difference in the
      intended movement velocity decoded by the two filters vanishes within 5 s, with a
      correlation coefficient of 0.99 between the two decoded velocities over the
      session length. We also find that the steady-state Kalman filter reduces the
      computational load (algorithm execution time) for decoding the firing rates of
      25+/-3 single units by a factor of 7.0+/-0.9. We expect that the gain in
      computational efficiency will be much higher in systems with larger neural
      ensembles. The steady-state filter can thus provide substantial runtime
      efficiency at little cost in terms of estimation accuracy. This far more
      efficient neural decoding approach will facilitate the practical implementation
      of future large-dimensional, multisignal neural interface systems.

PMID- 21078583
TI  - A case of levetiracetam-induced thrombocytopenia.
AB  - Rare cases of levetiracetam-induced thrombocytopenia have been reported in the
      literature. We report a case of glioblastoma multiforme and partial epilepsy
      treated with levetiracetam with subsequent development of thrombocytopenia. After
      ruling out all other possible causes of a decreased platelet count, we conclude
      that levetiracetam was the cause of this adverse event.

PMID- 21078584
TI  - Unilateral continuous subclinical paroxysmal activity: an unusual finding in a
      patient with recurrent absence status.
AB  - We report a patient with a history of rare generalised tonic-clonic seizures and
      recurrent absence status who was diagnosed with a rare variant of idiopathic
      generalised epilepsy and absence status epilepsy. No other pathology was
      identified and MRI was normal. During a follow-up of 17 years, we recorded a
      single unilateral continuous, strictly subclinical, paroxysmal activity which
      lasted for at least several hours. No control was observed under treatment with
      phenobarbital, lamotrigine and topiramate. Absence status was aggravated with
      carbamazepine and generalised tonic-clonic seizures were not controlled with
      ethosuximide. Total seizure control was only possible with sodium valproate,
      which caused weight gain, and the patient has remained seizure-free for the past
      10 years under 1,000 mg/d valproate and 200 mg/d topiramate. The recorded
      unilateral, long-lasting, subclinical spike-and-wave discharge is quite unusual
      for idiopathic generalised epilepsy and, in our opinion, occupies a transitional
      position between generalised and focal activity.

PMID- 21078585
TI  - Different dynamics of IL-15R activation following IL-15 cis- or trans
      presentation.
AB  - Interleukin (IL)-15 is a cytokine critical for the homeostasis and the function
      of NK cells, NK-T cells, and memory CD8+ T cells. IL-15 signals are delivered
      through the IL-15Rbeta and the common gamma (gamma(c)) receptor chains. The third
      receptor chain, IL-15Ralpha, confers specificity and high affinity for the
      cytokine. While IL-15 can activate with high affinity the trimeric receptor
      expressed by a target cell (cis-presentation), IL-15Ralpha is also known to trans
      present IL-15 with high affinity to target cells expressing the IL
      15Rbeta/gamma(c) complex. In order to compare the IL-15 cis- and trans
      presentation processes, and using a T cell line expressing both IL
      15Ralpha/beta/gamma(c) and IL-15Rbeta/gamma(c), we analyzed cell surface receptor
      chain down-modulation, cytokine internalization and signaling responses induced
      either with IL-15 (cis-presentation) or with RLI, a protein resulting from fusion
      between IL-15 and an extended IL-15Ralpha sushi domain, that mimics trans
      presentation. Whereas IL-15 bound with high affinity to IL
      15Ralpha/beta/gamma(c), RLI bound with a similar high affinity to IL
      15Rbeta/gamma(c). The kinetics of cell surface IL-15R down-modulation were slower
      following RLI treatment than after IL-15 treatment, as were the kinetics of RLI
      internalization, which was slower than that of IL-15. IL-15 and RLI dose
      dependently induced the activation of similar signaling pathways. However, the
      kinetics and duration of these activations were markedly different, RLI-induced
      signaling, being slower, but more prolonged than that induced by IL-15, although
      the final proliferative responses at 48 h were similar. These findings
      collectively indicate that IL-15 cis- and trans-presentation mechanisms lead to
      different dynamics of receptor activation and signal transduction, with cis
      presentation inducing fast and transient responses, and trans-presentation
      inducing slower, more persistent ones. They provide clues for a better
      understanding of how IL-15 action is controlled, and how it plays a key role in
      the coordination between innate and adaptative immunity.

PMID- 21078586
TI  - Unperturbed islet alpha-cell function examined in mouse pancreas tissue slices.
AB  - Critical investigation into alpha-cell biology in health and diabetes has been
      sparse and at times inconsistent because of the technical difficulties with
      employing conventional strategies of isolated islets and dispersed single cells.
      An acute pancreas slice preparation was developed to overcome the enzymatic and
      mechanical perturbations inherent in conventional islet cell isolation
      procedures. This preparation preserves intra-islet cellular communication and
      islet architecture in their in situ native state. alpha-Cells within tissue
      slices were directly assessed by patch pipette and electrophysiologically
      characterized. The identity of the patched cells was confirmed by biocytin dye
      labelling and immunocytochemistry. alpha-Cells in mouse pancreas slices exhibited
      well-described features of I(Na) (excitable at physiological membrane potential),
      I(KATP), small cell size, low resting membrane conductance, and inducible low and
      high voltage-activated I(Ca), the latter correlating with exocytosis determined
      by capacitance measurements. In contrast to previous reports, our large unbiased
      sampling of alpha-cells revealed a wide range distribution of all of these
      parameters, including the amount of K(ATP) conductance, Na+ and Ca2+ current
      amplitudes, and capacitance changes induced by a train of depolarization pulses.
      The proposed pancreas slice preparation in combination with standard patch
      clamping technique allowed large sampling and rapid assessment of alpha-cells,
      which revealed a wide distribution in alpha-cell ion channel properties. This
      specific feature explains the apparent inconsistency of previous reports on these
      alpha-cell ion channel properties. Our innovative approach will enable future
      studies into elucidating islet alpha-cell dysregulation occurring during
      diabetes.

PMID- 21078587
TI  - Testosterone restores respiratory long term facilitation in old male rats by an
      aromatase-dependent mechanism.
AB  - Steroidal sex hormones play an important role in the neural control of breathing.
      Previous studies in our laboratory have shown that gonadectomy in young male rats
      (3 months) eliminates a form of respiratory plasticity induced by intermittent
      hypoxia, known as long term facilitation (LTF). Testosterone replenishment
      restores LTF in gonadectomized male rats, and this is dependent on the conversion
      of testosterone to oestradiol by aromatase. By middle age (12 months), male rats
      no longer exhibit LTF of hypoglossal motor output; phrenic LTF is significantly
      reduced, and this persists into old age. We tested the hypothesis that LTF can be
      restored in old male rats by administration of testosterone. Intact Fischer 344
      rats (>20 months) were implanted with Silastic tubing containing testosterone
      (T), T plus an aromatase inhibitor (T+ADT), or 5alpha-dihydrotestosterone (DHT),
      a form of testosterone not converted to oestradiol. One week post-surgery, LTF of
      hypoglossal and phrenic motor output was measured. By comparison with control
      rats, hypoglossal LTF was increased in testosterone-treated rats, with levels
      approaching that of normal young rats. LTF was not restored in T+ADT or DHT
      treated rats. Aromatase levels in hypoglossal and phrenic nuclei did not change
      with age. As serum testosterone levels did not decline with age, local
      bioavailability of testosterone in old rats may be a limiting factor in the
      expression of this form of respiratory plasticity. Our findings suggest that
      testosterone supplementation could potentially be used to enhance upper airway
      control in the elderly.

PMID- 21078588
TI  - Irritating channels: the case of TRPA1.
AB  - Transient receptor potential (TRP) channels have been extensively studied over
      the past years. Yet, in most cases, the gating mechanisms of these polymodal
      cation channels still remain a puzzle. Using the nociceptive channel TRPA1 as an
      example, we discuss the role of dynamic regulation of the pore size (pore
      dilatation) on channel gating. Additionally, we critically revise current
      knowledge of the role of intracellular domains, such as ankyrin repeats and EF
      hand motifs, in channel activation and function. Finally, we assess some problems
      inherent to activation of TRPA1 by the reaction of electrophilic compounds with
      the nucleophilic thiol sink of N-terminal reactive cysteines.

PMID- 21078589
TI  - The dynamics of single spike-evoked adenosine release in the cerebellum.
AB  - The purine adenosine is a potent neuromodulator in the brain, with roles in a
      number of diverse physiological and pathological processes. Modulators such as
      adenosine are difficult to study as once released they have a diffuse action
      (which can affect many neurones) and, unlike classical neurotransmitters, have no
      inotropic receptors. Thus rapid postsynaptic currents (PSCs) mediated by
      adenosine (equivalent to mPSCs) are not available for study. As a result the
      mechanisms and properties of adenosine release still remain relatively unclear.
      We have studied adenosine release evoked by stimulating the parallel fibres in
      the cerebellum. Using adenosine biosensors combined with deconvolution analysis
      and mathematical modelling, we have characterised the release dynamics and
      diffusion of adenosine in unprecedented detail. By partially blocking K+
      channels, we were able to release adenosine in response to a single stimulus
      rather than a train of stimuli. This allowed reliable sub-second release of
      reproducible quantities of adenosine with stereotypic concentration waveforms
      that agreed well with predictions of a mathematical model of purine diffusion. We
      found no evidence for ATP release and thus suggest that adenosine is directly
      released in response to parallel fibre firing and does not arise from
      extracellular ATP metabolism. Adenosine release events showed novel short-term
      dynamics, including facilitated release with paired stimuli at millisecond
      stimulation intervals but depletion-recovery dynamics with paired stimuli
      delivered over minute time scales. These results demonstrate rich dynamics for
      adenosine release that are placed, for the first time, on a quantitative footing
      and show strong similarity with vesicular exocytosis.

PMID- 21078590
TI  - Effect of P2 receptor blockade with pyridoxine on sympathetic response to
      exercise pressor reflex in humans.
AB  - During exercise, sympathetic nervous system activity increases and this
      contributes to an increase in blood pressure (i.e. exercise pressor reflex).
      Although animal studies suggest that purinergic P2 receptors on thin fibre
      sensory nerves are stimulated and evoke this reflex, human data are lacking. In
      this study, young healthy volunteers performed fatiguing isometric handgrip
      before and after a local infusion of pyridoxine (i.e. vitamin B(6)) into the
      'isolated' circulation of the human forearm. Pyridoxine is converted into a P2
      purinoceptor antagonist. Muscle sympathetic nerve activity and blood pressure
      responses to fatiguing handgrip and post-exercise circulatory occlusion were
      significantly less after pyridoxine than they were before. These effects were not
      observed after infusion of saline. These data suggest that P2 receptors
      contribute to the exercise pressor reflex in humans.

PMID- 21078591
TI  - Role of blood flow in carotid body chemoreflex function in heart failure.
AB  - Peripheral chemoreflex sensitivity is potentiated in clinical and experimental
      chronic heart failure (CHF). Blood supply to tissues is inevitably reduced in
      CHF. However, it remains poorly understood whether the reduced blood flow is the
      cause of increased peripheral chemoreflex sensitivity in CHF. This work
      highlights the effect of chronically reduced blood flow to the carotid body (CB)
      on peripheral chemoreflex function in rabbits. In pacing-induced CHF rabbits,
      blood flow in the carotid artery was reduced by 36.4 +/- 5.2% after 3 weeks of
      pacing. For comparison, a similar level of blood flow reduction was induced by
      carotid artery occlusion (CAO) over a similar 3 week time course without pacing.
      CB blood supply was reduced by similar levels in both CHF and CAO rabbits as
      measured with fluorescent microspheres. Compared with sham rabbits, CAO enhanced
      peripheral chemoreflex sensitivity in vivo, increased CB chemoreceptor activity
      in an isolated CB preparation and decreased outward potassium current (Ik) in CB
      glomus cells to levels similar to those that were observed in CHF rabbits. In CAO
      CB compared to sham, neural nitric oxide (NO) synthase (nNOS) expression and NO
      levels were suppressed, and angiotensin II (Ang II) type 1 receptor (AT1-R)
      protein expression and Ang II concentration were elevated; these changes were
      similar to those seen in the CB from CHF rabbits. A NO donor and AT1-R antagonist
      reversed CAO-enhanced chemoreflex sensitivity. These results suggest that a
      reduction of blood flow to the CB is involved in the augmentation of peripheral
      chemoreflex sensitivity in CHF.

PMID- 21078592
TI  - Regulation of erythropoietin production.
AB  - The hormone erythropoietin (Epo) maintains red blood cell mass by promoting the
      survival, proliferation and differentiation of erythrocytic progenitors.
      Circulating Epo originates mainly from fibroblasts in the renal cortex. Epo
      production is controlled at the transcriptional level. Hypoxia attenuates the
      inhibition of the Epo promoter by GATA-2. More importantly, hypoxia promotes the
      availability of heterodimeric (alpha/beta) hypoxia-inducible transcription
      factors (predominantly HIF-2) which stimulate the Epo enhancer. The HIFs are
      inactivated in normoxia by enzymatic hydroxylation of their alpha-subunits. Three
      HIF-alpha prolyl hydroxylases (PHD-1, -2 and -3) initiate proteasomal degradation
      of HIF-alpha, while an asparaginyl hydroxylase ('factor inhibiting HIF-1', FIH-1)
      inhibits the transactivation potential. The HIF-alpha hydroxylases contain Fe(2+)
      and require 2-oxoglutarate as co-factor. The in vivo response is dynamic, i.e.
      the concentration of circulating Epo increases initially greatly following an
      anaemic or hypoxaemic stimulus and then declines despite continued hypoxia. Epo
      and angiotensin II collaborate in the maintenance of the blood volume. Whether
      extra-renal sites (brain, skin) modulate renal Epo production is a matter of
      debate. Epo overproduction results in erythrocytosis. Epo deficiency is the
      primary cause of the anaemia in chronic kidney disease and a contributing factor
      in the anaemias of chronic inflammation and cancer. Here, recombinant analogues
      can substitute for the hormone.

PMID- 21078593
TI  - Electrophysiological evidence for distinct vagal pathways mediating CCK-evoked
      motor effects in the proximal versus distal stomach.
AB  - Intravenous cholecystokinin octapeptide (CCK-8) elicits vago-vagal reflexes that
      inhibit phasic gastric contractions and reduce gastric tone in urethane
      anaesthetized rats. A discrete proximal subdivision of the ventral gastric vagus
      nerve (pVGV) innervates the proximal stomach, but the fibre populations within it
      have not been characterized previously.We hypothesized that I.V. CCK-8 injection
      would excite inhibitory efferent outflow in the pVGV, in contrast to its
      inhibitory effect on excitatory efferent outflow in the distal subdivision
      (dVGV), which supplies the distal stomach. In each VGV subdivision, a dual
      recording technique was used to record afferent and efferent activity
      simultaneously, while also monitoring intragastric pressure (IGP). CCK-8 dose
      dependently (100-1000 pmol kg(-1), I.V.) reduced gastric tone, gastric
      contractile activity and multi-unit dVGV efferent discharge, but increased pVGV
      efferent firing. Single-unit analysis revealed a minority of efferent fibres in
      each branch whose response differed in direction from the bulk response.
      Unexpectedly, efferent excitation in the pVGV was significantly shorter lived and
      had a significantly shorter decay half-time than did efferent inhibition in the
      dVGV, indicating that distinct pathways drive CCK-evoked outflow to the proximal
      vs. the distal stomach. Efferent inhibition in the dVGV began several seconds
      before, and persisted significantly longer than, simultaneously recorded dVGV
      afferent excitation.Thus, dVGV afferent excitation could not account for the
      pattern of dVGV efferent inhibition. However, the time course of dVGV afferent
      excitation paralleled that of pVGV efferent excitation. Similarly, the duration
      of CCK-8-evoked afferent responses recorded in the accessory celiac branch of the
      vagus (ACV) matched the duration of dVGV efferent responses. The observed
      temporal relationships suggest that postprandial effects on gastric complicance
      of CCK released from intestinal endocrine cells may require circulating
      concentrations to rise to levels capable of exciting distal gastric afferent
      fibres, in contrast to more immediate effects on distal gastric contractile
      activity mediated via vago-vagal reflexes initiated by paracrine excitation of
      intestinal afferents.

PMID- 21078594
TI  - Renal mechanisms contributing to the antihypertensive action of soluble epoxide
      hydrolase inhibition in Ren-2 transgenic rats with inducible hypertension.
AB  - In the present study, we examined the effects of soluble epoxide hydrolase (sEH)
      inhibition on the development of angiotensin II-dependent hypertension and on
      renal function in transgenic rats with inducible expression of the mouse renin
      gene (strain name Cyp1a1-Ren-2). Hypertension was induced in these rats by indole
      3-carbinol (I3C; 0.3% in the diet) for 12 days. The sEH inhibitor cis-4-[4-(3
      adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) was given in two
      doses (13 or 26 mg l-1) in drinking water. Blood pressure (BP), body weight (BW)
      and renal excretory parameters were monitored in conscious animals during the
      experiment. Renal haemodynamics was assessed at the end of treatment in
      anaesthetized rats. I3C administration resulted in severe hypertension with a
      rise in systolic BP from 118 +/- 2 to 202 +/- 3 mmHg, a loss of BW from 266 +/- 5
      to 228 +/- 4 g and a rise in proteinuria from 14 +/- 2 to 34 +/- 3 mg day-1. Both
      doses of c-AUCB significantly attenuated the development of hypertension
      (systolic BP of 181 +/- 4 and 176 +/- 4 mmHg, respectively), the loss in BW (256
      +/- 4 and 259 +/- 3 g, respectively) and the degree of proteinuria (27 +/- 2 and
      25 +/- 3 mg day-1, respectively) to a similar extent. Moreover, c-AUCB prevented
      the reduction in renal plasma flow (5.4 +/- 0.4 vs. 4.6 +/- 0.3 ml min-1 g-1) and
      significantly increased sodium excretion (0.84 +/- 0.16 vs. 0.38 +/- 0.08 MUmol
      min-1 g-1) during I3C administration. These data suggest that the oral
      administration of c-AUCB displays antihypertensive effects in Ren-2 transgenic
      rats with inducible malignant hypertension via an improvement of renal function.

PMID- 21078595
TI  - SOD1 targeted to the mitochondrial intermembrane space prevents motor neuropathy
      in the Sod1 knockout mouse.
AB  - Motor axon degeneration is a critical but poorly understood event leading to
      weakness and muscle atrophy in motor neuron diseases. Here, we investigated
      oxidative stress-mediated axonal degeneration in mice lacking the antioxidant
      enzyme, Cu,Zn superoxide dismutase (SOD1). We demonstrate a progressive motor
      axonopathy in these mice and show that Sod1(-/-) primary motor neurons extend
      short axons in vitro with reduced mitochondrial density. Sod1(-/-) neurons also
      show oxidation of mitochondrial--but not cytosolic--thioredoxin, suggesting that
      loss of SOD1 causes preferential oxidative stress in mitochondria, a primary
      source of superoxide in cells. SOD1 is widely regarded as the cytosolic isoform
      of superoxide dismutase, but is also found in the mitochondrial intermembrane
      space. The functional significance of SOD1 in the intermembrane space is unknown.
      We used a transgenic approach to express SOD1 exclusively in the intermembrane
      space and found that mitochondrial SOD1 is sufficient to prevent biochemical and
      morphological defects in the Sod1(-/-) model, and to rescue the motor phenotype
      of these mice when followed to 12 months of age. These results suggest that SOD1
      in the mitochondrial intermembrane space is fundamental for motor axon
      maintenance, and implicate oxidative damage initiated at mitochondrial sites in
      the pathogenesis of motor axon degeneration.

PMID- 21078596
TI  - Of mice and men: filling gaps in the TBC1D1 story.

PMID- 21078597
TI  - What does the membrane K(ATP) channel really do in skeletal muscle?

PMID- 21078598
TI  - The 'connexin' between astrocytes, ATP and central respiratory chemoreception.

PMID- 21078599
TI  - Early dating influences long-term synaptic partnerships.

PMID- 21078600
TI  - Changing our thinking about walking.

PMID- 21078601
TI  - Sympathetic coronary vasomotor control: are women really the weaker sex?

PMID- 21078602
TI  - The curse of the sympathetic nervous system: are men or women more unfortunate?

PMID- 21078604
TI  - Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant
      Enterobacteriaceae isolates.
AB  - BACKGROUND: the emergence of carbapenemases in Enterobacteriaceae is driving a
      search for therapeutic alternatives. We tested ACHN-490, a sisomicin derivative
      that evades all plasmid-mediated aminoglycoside-modifying enzymes, against 82
      carbapenem-resistant Enterobacteriaceae isolates. Comparators included
      internationally and locally available aminoglycosides. Methods The isolates
      variously had KPC (n = 12), SME-1 (n = 1), IMP (n = 13), VIM (n = 5), NDM (n =
      17) or OXA-48 (n = 19) carbapenemases, or had combinations of impermeability with
      AmpC (n = 5) or extended-spectrum beta-lactamases (n = 10). They included 53
      Klebsiella spp., 19 Enterobacter spp., 6 Escherichia coli and 4 others; most were
      multiresistant. Genes were identified by PCR and sequencing; MICs were measured
      by CLSI agar dilution. RESULTS: ACHN-490 was active at <= 2 mg/L against all 65
      isolates with carbapenem resistance mechanisms other than NDM enzyme, mostly with
      MICs of 0.12-0.5 mg/L; isepamicin was active against 63/65 at <= 8 mg/L. In
      contrast, 35% were resistant to gentamicin at 4 mg/L, 61% to tobramycin at 4 mg/L
      and 20% to amikacin at 16 mg/L. However, 16 of the 17 isolates with NDM-1 enzyme
      were resistant to ACHN-490, with MICs >= 64 mg/L, and these were cross-resistant
      to all other human-use aminoglycosides tested. Their behaviour was associated
      with ArmA and RmtC 16S rRNA methylases. Apramycin (a veterinary aminoglycoside)
      retained its full activity, with MICs of 4-8 mg/L versus strains with armA or
      rmtC, though resistance was seen in one Klebsiella pneumoniae with AAC(3)-IV (MIC
      >= 256 mg/L). CONCLUSIONS: ACHN-490 has potent activity versus carbapenem
      resistant isolates, except those also harbouring 16S rRNA methylases; isepamicin
      is also widely active, though less potent than ACHN-490. Evasion of 16S rRNA
      methylases by apramycin is noteworthy and may provide a starting point for future
      aminoglycoside development.

PMID- 21078605
TI  - Measles-mumps-rubella revaccination; 18 months vs. 4-6 years of age: potential
      impacts of schedule changes.
AB  - OBJECTIVE: The policy of administering the second dose of measles-mumps-rubella
      (MMR) vaccine (MMR(2)) has recently changed in Iran, at age 1.5 years instead of
      4-6 years previously. The effects of such a change on the immune status of the
      individual are evaluated in this study. METHODS: Totally 249 and 228 children
      aged 18 months and 4- to 6-year-olds, respectively, with a documented receipt of
      primary MMR vaccine at the age of >= 1 year were enrolled. Before, and 4-6 weeks
      after MMR(2) administration, anti-MMR IgG antibody levels were measured using
      ELISA method. IgM antibody levels were also assessed in measles-rubella
      seronegative children that responded to MMR(2). Collected data for each component
      from both age groups were compared by using Fischer's exact probability and chi
      square tests. RESULTS: Before revaccination, measles seroimmunity rate was
      similar between the two groups, but rates to mumps and rubella were significantly
      higher in younger children-measles: 74 vs. 78.3%; mumps: 82.3 vs. 68.4% and
      rubella: 75% vs. 67%, respectively. After administration of MMR(2), all
      seroimmune subjects were IgG boosted. Except for rubella, older seronegative
      children showed significantly higher seroconvertion rate to MMR(2) and
      seroprevalence rates increased in vaccinees--measles: 98.2 vs. 94%, mumps: 97 vs.
      94.4% and rubella: 87 vs. 92.4%, respectively. Only few measles-rubella
      seronegative children showed IgM response to MMR(2). CONCLUSION: This study
      showed that the majority of younger children were susceptible to MMR infection
      before revaccination. Earlier age policy provides more protection against MMR in
      preschool-aged children. Rubella strain seems to be less potent than reported.

PMID- 21078603
TI  - Symmetrical choline-derived dications display strong anti-kinetoplastid activity.
AB  - OBJECTIVES: to investigate the anti-kinetoplastid activity of choline-derived
      analogues with previously reported antimalarial efficacy. METHODS: from an
      existing choline analogue library, seven antimalarial compounds, representative
      of the first-, second- and third-generation analogues previously developed, were
      assessed for activity against Trypanosoma and Leishmania spp. Using a variety of
      techniques, the effects of choline analogue exposure on the parasites were
      documented and a preliminary investigation of their mode of action was performed.
      RESULTS: the activities of choline-derived compounds against Trypanosoma brucei
      and Leishmania mexicana were determined. The compounds displayed promising anti
      kinetoplastid activity, particularly against T. brucei, to which 4/7 displayed
      submicromolar EC(50) values for the wild-type strain. Low micromolar
      concentrations of most compounds cleared trypanosome cultures within 24-48 h. The
      compounds inhibit a choline transporter in Leishmania, but their entry may not
      depend only on this carrier; T. b. brucei lacks a choline carrier and the mode of
      uptake remains unclear. The compounds had no effect on the overall lipid
      composition of the cells, cell cycle progression or cyclic adenosine
      monophosphate production or short-term effects on intracellular calcium levels.
      However, several of the compounds, displayed pronounced effects on the
      mitochondrial membrane potential; this action was not associated with production
      of reactive oxygen species but rather with a slow rise of intracellular calcium
      levels and DNA fragmentation. CONCLUSIONS: the choline analogues displayed strong
      activity against kinetoplastid parasites, particularly against T. b. brucei. In
      contrast to their antimalarial activity, they did not act on trypanosomes by
      disrupting choline salvage or phospholipid metabolism, instead disrupting
      mitochondrial function, leading to chromosomal fragmentation.

PMID- 21078606
TI  - Review: Antiplatelet drugs: what comes next?
AB  - Antiplatelet drugs are important components in the management of atherothrombotic
      vascular disease. However, several limitations restrict the safety and efficacy
      of current antiplatelet therapy in clinical practice. Interpatient variability
      and resistance to aspirin and/or clopidogrel has spurred efforts for the
      development of novel agents. Indeed, several antiplatelet drugs are at various
      stages of evaluation; those at advanced stage of development are the focus of
      this review.

PMID- 21078607
TI  - Exogenous L-arginine and HDL can alter LDL and ox-LDL-mediated platelet
      activation: using platelet P-selectin receptor numbers.
AB  - The aim of this study is to investigate the effects of exogenous L-arginine and
      HDL on LDL and oxidized LDL (ox-LDL)-mediated platelet activation. Adenosine
      diphosphate (ADP)-activated platelets have been incubated with lipoproteins with
      or without L-arginine. P-selectin receptor numbers per platelet have been
      measured by flow cytometry. After incubation with only L-arginine (without
      lipoproteins), platelet nitric oxide (NO) levels and P-selectin receptor numbers
      significantly increased compared to the controls (P < .05). After incubation with
      LDL or ox-LDL, receptor numbers of P-selectin significantly increased (P < .001).
      However, P-selectin receptor numbers in platelets treated with L-arginine + LDL
      or L-arginine + ox-LDL decreased compared to the levels in platelets treated with
      only LDL or ox-LDL (P < .01, P < .001, respectively). Addition of HDL to L
      arginine + ox-LDL caused significant reduction in P-selectin receptor numbers as
      in the control values (P < .001).We have concluded that L-arginine causes
      enhanced platelet NO levels and blocks the effects of LDL or ox-LDL on platelet P
      selectin receptor numbers and HDL also strengthens this effect of L-arginine.

PMID- 21078608
TI  - Global fibrinolytic capacity in neonatal sepsis.
AB  - In this study, we studied global fibrinolytic capacity (GFC) in newborn infants
      with sepsis. Sixty-one newborn infants, admitted to neonatal intensive care unit
      at Yuzuncu Yil University Hospital were enrolled in this study. White blood cell
      count, immature (I) / mature (M) neutrophil ratios, prothrombin time, and d-dimer
      levels were significantly higher in patient group than those of control group (P
      < .05). We found GFC to be significantly lower in the patient group compared to
      the control group (P < .05). The GFC value was negatively correlated to the
      Tollner scores but this correlation was not statistically significant (r = -.267,
      P = .095). Our findings showed that GFC decreases in severe neonatal sepsis;
      therefore, we suggest that GFC may be used for prognosis or in the early
      prediction of severe sepsis rather than the diagnosis of neonatal sepsis.

PMID- 21078609
TI  - Safety and efficacy of thrombin-JMI: a multidisciplinary expert group consensus.
AB  - BACKGROUND: The use of bovine thrombin has been an effective approach to aiding
      hemostasis during surgery for over 60 years. Its use has a reported association
      with the development of antibodies to coagulation factors with limited evidence
      to the clinical significance. METHODS: The Collaborative Delphi survey
      methodology was used to develop a consensus on specified topic areas from a panel
      of 12 surgeons/scientists who have had experience with topical thrombins; it
      consisted of 2 rounds of a Web-based survey and a final live discussion. RESULTS:
      Some key issues that reached consensus included: bovine, human plasma-derived and
      recombinant human thrombin are equally effective hemostatic agents with similar
      adverse event rates, and immunogenicity to a topical protein rarely translate
      into adverse events. CONCLUSIONS: Although a risk of immunogenicity is associated
      with all topical thrombins, no conclusive clinical evidence is available that
      these antibodies have any significant effect on short- and long-term clinical
      consequences.

PMID- 21078610
TI  - Evaluation and treatment of neonatal thrombus formation in 17 patients.
AB  - INTRODUCTION: Thrombosis is a rare but serious event in neonates. Perinatal risk
      factors associated with the developing hemostatic system increase the risk of
      thromboembolism. Treatment protocols vary between different centers. In this
      study, thrombosis and subsequent treatment were evaluated in 17 neonates
      hospitalized in a neonatal intensive care unit. This is the largest series
      reported to date. METHOD: From January 2007 to December 2009, thrombosis was
      diagnosed in 17 newborns hospitalized in a neonatal intensive care unit. Most
      were treated with recombinant tissue plasminogen activator (r-tPA) and enoxaparin
      as anticoagulant therapy. RESULTS: Eleven courses of r-tPA therapy were
      administered to 10 patients. Sixteen patients received low-molecular-weight
      heparin (LMWH) treatment. None of the patients had hemorrhagic complications due
      to therapy. Recurrence was observed in 1 patient 1.5 months after the first
      course of r-tPA and retreatment was performed. A complete decrease in thrombus
      size was achieved in 9 patients and a partial decrease in 5 patients. One patient
      died before treatment was initiated; another died at the end of the first day of
      treatment and thus could not be evaluated. One patient who had a homozygous
      mutation for factor V Leiden did not respond to treatment and the extremity
      involved was amputated. CONCLUSIONS: Thrombosis in neonates is a multifactorial
      disorder. Treatment consisting of r-tPA and an anticoagulant was shown to be a
      safe and effective approach to clot dissolution in neonates.

PMID- 21078611
TI  - Genetic mutations in Turkish population with pulmonary embolism and deep venous
      thrombosis.
AB  - Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired
      risk factors increase the risk of VTE. We evaluated the relationship between
      factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A),
      methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen
      activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population.
      In all, 80 patients with VTE and 104 controls were included. Heterozygous factor
      V Leiden (FVL) mutation was significantly higher among patients (P = .04) with
      allele frequency of 6.3% (P = .01). Heterozygous PT G20210A mutation was also
      significantly higher among patients (P = .001) with allele frequency of 6.9% (P =
      .003). MTHFR 677TT genotype was significantly higher in patients (P = .009) with
      allele frequency of 23.8% (P = .005). No significant difference was found in FV
      A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele
      frequencies (P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR
      C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations,
      and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish
      population.

PMID- 21078612
TI  - Reliability and validity of 5 databases for the identification of warfarin
      medication interactions.
AB  - Databases are used to screen for warfarin-medication interactions. We measured
      the reliability and validity of 5 databases. Databases were queried for 30
      medications identified as having varying degrees of interactions with warfarin in
      a recent systematic literature review. Reliability was measured by the percentage
      agreement between the databases for each interaction and validity was measured by
      agreement between each database and the systematic literature review. All of the
      databases and the systematic review agreed on 14 medications (47%). There were 5
      medications (17%) where all databases reported an interaction, but no interaction
      was noted by the systematic review. The databases did not agree on the remaining
      11 medications (37%). Four of these interactions were of moderate or greater
      clinical significance. These commonly used databases frequently do not agree on
      the occurrence of warfarin-medications interactions, and some interactions
      identified by the best clinical evidence were not identified in several
      databases.

PMID- 21078613
TI  - The effect of the acute submaximal exercise on thrombin activatable fibrinolysis
      inhibitor levels in young sedentary males.
AB  - Depending on type, duration, and intensity of the exercise, changes occur in
      hemostasis. In this study, we evaluated the changes in the parameters of
      coagulation and fibrinolytic systems that happened after the submaximal aerobic
      exercises by bicycle ergomater. Twelve healthy male participants whose ages were
      between 21 and 28 have been included. The venous samples have been drawn before
      the exercise as well as at the 0 th, 15th, and 60th minutes after the submaximal
      exercise. The values of prothrombin time (PT), active partial thromboplastin time
      (aPTT), D-dimer, fibrinogen, plasminogen activator inhibitor 1 (PAI-1) and
      thrombin-activatable fibrinolysis inhibitor (TAFI) have been measured.
      Plasminogen activator inhibitor 1 values have shown an insignificant increase
      after exercise (P = .328), whereas, it has decreased significantly during the
      resting period (P = .033) Postexercise 15th and 60th minutes TAFI values have
      decreased significantly comparing to basal and postexercise (0 th minute) values
      (P = .001). Fibrinolytic system activation is observed after acute submaximal
      aerobic exercise of sedentary healthy participants.

PMID- 21078614
TI  - A multicenter pilot study to estimate the prevalence of bovine and human
      coagulation antibodies in the general US population.
AB  - Antibodies to bovine and human coagulation proteins have been reported to develop
      in some patients receiving perioperative exposure to topical bovine thrombin. To
      estimate the prevalence of antihuman and antibovine thrombin and factor V
      antibodies in the general population, this multicenter pilot study in 278
      participants was undertaken. Of the participants, 88% had no detectable
      antibodies by enzyme-linked immunosorbent assay (ELISA). Cumulatively 22 (7.9%)
      of 278 of the participants were positive for at least 1 of the antibovine
      antibodies and only 11 (4%) of 278 were positive for human thrombin antibodies.
      No participants had antihuman factor V/Va antibodies. Antibodies were found in
      21% of participants with no history of surgery, transfusion, or pregnancy. In
      participants without a surgical history, thus a low likelihood of bovine thrombin
      exposure, 7.9% (9 of 114) had antibovine antibodies and 3.5% (4 of 114) had human
      antithrombin antibodies, suggesting that antibodies may arise from contact with
      antigenic sources other than bovine-derived thrombin.

PMID- 21078615
TI  - An anti-von Willebrand factor aptamer reduces platelet adhesion among patients
      receiving aspirin and clopidogrel in an ex vivo shear-induced arterial
      thrombosis.
AB  - The von Willebrand factor (vWF) aptamer, ARC1779 that blocks the binding of vWF
      A1-domain to platelet glycoprotein 1b (GPIb) at high shear, may deliver a site
      specific antithrombotic effect. We investigated the efficiency of ARC1779 on
      platelet function in patients with coronary artery disease (CAD) on double
      antiplatelet therapy. Blood from patients taking aspirin and clopidogrel and from
      normal volunteers was treated ex vivo with ARC1779 or abciximab, either prior to
      perfusion (pretherapy) or 10 minutes following the initiation of perfusion
      (posttherapy) on damaged arteries. Under pre- but not posttherapy, platelet
      adhesion was significantly reduced by ARC1779 at 83 and 250 nmol/L and by
      abciximab (100 nmol/L) versus placebo (4.8, 3.8, and 2.9 vs 7.3 platelets *
      10(6)/cm(2), P < .05). In contrast to abciximab, ARC1779 did not significantly
      affect platelet aggregation, P-selectin expression, and platelet-leukocyte
      binding. These proof-of-concept data may constitute the framework for randomized
      clinical investigations of this novel antiplatelet therapy among patients with
      CAD.

PMID- 21078616
TI  - The hemostatic system in patients with type 2 diabetes with and without
      cardiovascular disease.
AB  - The contribution of the hemostatic system in the development of cardiovascular
      disease (CVD) in patients with type 2 diabetes is not completely defined. The aim
      of this study was to elucidate associations of hemostatic factors with the
      development of CVD in patients with type 2 diabetes. Patients with type 2
      diabetes without CVD (n = 113), with CVD (n = 94), and controls without CVD (n =
      100) were enrolled in this study. Several hemostatic markers were measured. A
      disturbed hemostatic balance in patients with type 2 diabetes was observed as
      illustrated by hypofibrinolysis and increased levels of von Willebrand factor
      (vWF) and plasminogen-activator inhibitor 1 (PAI-1). Patients with type 2
      diabetes with CVD have more thrombin generation compared to patients without CVD.
      This hemostatic imbalance might contribute to the development of CVD in patients
      with type 2 diabetes.

PMID- 21078617
TI  - Coagulation activity in elderly patients with hip fracture measured by
      prothrombin fragment 1 + 2 in urine.
AB  - OBJECTIVE: The purpose of this study was to document the uF1 + 2 excretion in
      elderly patients during and after a hip fracture (HF). METHODS: The study was a
      prospective pilot study. Spot urine samples were collected immediately after
      admission and every morning until surgery. After surgery, urine samples were
      collected on days 1, 5, 7, 14, and at follow-up on day 90 (+/-10). RESULTS: A
      total of 24 women and 7 men with HF completed the study. The median uF1 + 2 level
      was significantly increased on the day of admission relative to the median level
      at follow-up. Maximum levels were seen on day 1 with a decreasing tendency until
      follow-up. Patients treated with a hemiarthroplasty had higher median uF1 + 2
      levels on all days compared with patients treated with osteosynthesis.
      CONCLUSION: A substantial coagulation activity, indicated by high median levels
      of uF1 + 2, was seen at admission and during the first week after HF.

PMID- 21078618
TI  - Outcome of long-term prophylaxis after cerebral hemorrhage in a patient with
      severe hemophilia B.
AB  - Reports of intracerebral hemorrhage (ICH) in patients with hemophilia B are
      relatively rare. We describe the first clinical results of the use of a
      monoclonal antibody purified factor IX (FIX) concentrate (Mononine) after an ICH
      and the long-term outcome of prophylaxis with this product to prevent
      recurrences. A 44-year-old male with severe hemophilia B was referred to our
      department because of nausea, vomiting, left lower limb hemiplegia, and left arm
      paresis. Computed tomography (CT) revealed a right frontal intraparenchymal
      bleed. The patient was treated with replacement therapy with FIX for 40 days.
      Computed tomography scans performed on day 40 after the event showed complete
      disappearance of the cerebral hematoma from the parenchymal tissue. Subsequently,
      the patient received 25.6 IU/kg(-1) of FIX twice a week. At the 48-month follow
      up visit, no more major or minor bleeding events had occurred. Long-term
      prophylaxis after ICH is recommended.

PMID- 21078622
TI  - Conventional and Mendelian randomization analyses suggest no association between
      lipoprotein(a) and early atherosclerosis: the Young Finns Study.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is an established risk factor for coronary
      disease and stroke, but mechanisms underlying this association are unknown. We
      examined the association of Lp(a) with early atherosclerosis by using
      conventional epidemiologic analysis and a Mendelian randomization analysis. The
      latter utilized genetic variants that are associated with Lp(a) to estimate
      causal effect. METHODS: A prospective population-based cohort study of 939 men
      and 1141 women was conducted. Lp(a) was measured repeatedly at mean ages 17 and
      38 years. Measurements of carotid intima-media thickness (IMT) and brachial flow
      mediated dilation (FMD) at mean ages 32 and 38 years were used to determine the
      level and 6-year progression of subclinical atherosclerosis. Lp(a)-related
      genetic variant, rs783147, was identified by a genome wide association analysis
      (P = 3.1 * 10-58), and a genetic score was constructed based on 10 Lp(a)-related
      variants. Mendelian randomization test was performed using a two-stage
      instrumental variables analysis. RESULTS: rs783147 and the genetic score were
      strong instruments for nonconfounded Lp(a) levels (F-statistics 269.6 and 446.0
      in the first-stage instrumental variable analysis). However, Lp(a) levels were
      not associated with the levels of or change in IMT or FMD in any of the
      conventional and instrumental variables tests. The null finding was observed both
      with rs783147 and the genetic score as instruments and remained unchanged after
      adjustment for clinical characteristics, such as age, sex, HDL and LDL
      cholesterol, ApoB, systolic and diastolic blood pressure, diabetes and smoking.
      CONCLUSIONS: Data from conventional and Mendelian randomization analyses provide
      no support for early atherogenic effects of increased Lp(a) levels.

PMID- 21078623
TI  - NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer
      segment formation, and for sperm development.
AB  - Nephronophthisis (NPHP) is an autosomal recessive kidney disease that is often
      associated with vision and/or brain defects. To date, 11 genes are known to cause
      NPHP. The gene products, while structurally unrelated, all localize to cilia or
      centrosomes. Although mouse models of NPHP are available for 9 of the 11 genes,
      none has been described for nephronophthisis 4 (Nphp4). Here we report a novel,
      chemically induced mutant, nmf192, that bears a nonsense mutation in exon 4 of
      Nphp4. Homozygous mutant Nphp4(nmf192/nmf192) mice do not exhibit renal defects,
      phenotypes observed in human patients bearing mutations in NPHP4, but they do
      develop severe photoreceptor degeneration and extinguished rod and cone ERG
      responses by 9 weeks of age. Photoreceptor outer segments (OS) fail to develop
      properly, and some OS markers mislocalize to the inner segments and outer nuclear
      layer in the Nphp4(nmf192/nmf192) mutant retina. Despite NPHP4 localization to
      the transition zone in the connecting cilia (CC), the CC appear to be normal in
      structure and ciliary transport function is partially retained. Likewise,
      synaptic ribbons develop normally but then rapidly degenerate by P14. Finally,
      Nphp4(nmf192/nmf192) male mutants are sterile and show reduced sperm motility and
      epididymal sperm counts. Although Nphp4(nmf192/nmf192) mice fail to recapitulate
      the kidney phenotype of NPHP, they will provide a valuable tool to further
      elucidate how NPHP4 functions in the retina and male reproductive organs.

PMID- 21078625
TI  - Long-term effectiveness and safety of TNF-blocking agents in daily clinical
      practice: results from the Dutch Rheumatoid Arthritis Monitoring register.
AB  - OBJECTIVES: Experience with anti-TNF agents for a decade can be used to research
      the safety and effectiveness of anti-TNF agents in the long term. The objective
      of this article is to describe drug survival, disease activity, daily
      functioning, quality of life and adverse events of TNF-blocking agents in daily
      clinical practice after 5 years of follow-up. METHODS: Data from the Dutch
      Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used
      for analyses (5-year follow-up, n=174). Drug survival and time to first serious
      infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome
      measures at several follow-up moments were analysed per intention to treat and
      per protocol. RESULTS: The 5-year drug survival of the first anti-TNF was 45%,
      and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was
      5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients
      who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were
      still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d.
      0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2).
      Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100
      patient-years, respectively. CONCLUSION: Five-year follow-up of RA patients
      treated with TNF-blocking agents showed a 60% drug survival accompanied by
      sustained low disease activity, normalized function and quality of life similar
      to that in the general population. The benefit to risk ratio for long-term TNF
      blocking therapy remains favourable.

PMID- 21078626
TI  - Registries in chronic disease: coming your way soon? Registries--problems,
      solutions and the future.

PMID- 21078628
TI  - Identification of BANK1 polymorphisms by unlabelled probe high resolution
      melting: association with systemic lupus erythematosus susceptibility and
      autoantibody production in Han Chinese.
AB  - OBJECTIVES: The three functional SNPs of BANK1 (rs10516487, rs17266594 and
      rs3733197) have been shown to be associated with SLE in Caucasian populations.
      The aim of this study was to investigate whether the association of BANK1
      polymorphisms with SLE could be replicated in a Chinese population and whether
      the autoantibody production is relevant to BANK1 polymorphisms. METHODS:
      Genotyping of three variants in BANK1 was carried out by unlabelled probe high
      resolution melting (HRM) assay in 264 SLE cases and 268 controls in a Chinese Han
      population living in Shanghai region. The genotype frequencies of the detected
      polymorphisms were analysed in relation to the production of autoantibodies (ANA,
      anti-dsDNA, anti-RNP, anti-SSA, anti-SSB and anti-Smith) in SLE patients.
      RESULTS: Samples with the target genotypes were accurately detected and easily
      distinguishable by unlabelled probe HRM assay. The frequencies of the rs10516487
      C allele and the rs17266594 T allele were significantly increased compared with
      the controls (C allele: 88.6 vs 83.2%, P = 0.011; T allele: 88.3 vs 83.2%, P =
      0.019). However, the frequencies of the rs3733197 G allele were not associated
      with SLE (G allele: 79.9 vs 79.1%, P = 0.741). The rs10516487 and rs17266594
      polymorphisms were significantly associated with high-titre ANA (>=1 : 320) and
      production of anti-SSA antibodies in SLE patients compared with the control
      subjects. CONCLUSIONS: Genotyping using unlabelled probes is a rapid, accurate
      and cost-effective closed-tube method. This study implies that rs10516487 and
      rs17266594 polymorphisms might contribute to individual susceptibility to SLE and
      influence the ANA/SSA autoantibody response in SLE patients in Chinese
      population.

PMID- 21078627
TI  - Risk of adverse events including serious infections in rheumatoid arthritis
      patients treated with tocilizumab: a systematic literature review and meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: To assess the risk of adverse events (AEs) in patients with RA treated
      with tocilizumab, an IL-6 receptor antibody, in published randomized controlled
      trials (RCTs). METHODS: A systematic literature search was conducted using the
      Cochrane library, PUBMED and EMBASE for all RCTs (of the use of tocilizumab for
      RA) until September 2009. Fixed effect meta-analyses were conducted to compare
      the incidence of AEs after treatment with tocilizumab 8 and 4 mg/kg in
      combination with MTX, and 8 mg/kg tocilizumab monotherapy, with controls. Pooled
      summary odds ratios (ORs) were calculated using the Mantel-Haenszel method.
      RESULTS: Six trials were analysed (four trials included 8 mg/kg tocilizumab and
      MTX combination therapy, three of which also assessed the 4 mg/kg dose). Three
      studies assessed tocilizumab monotherapy at 8 mg/kg. Pooled ORs revealed
      statistical significance for an increased risk of AEs in the 8 mg/kg combination
      group compared with controls (OR = 1.53; 95% CI 1.26, 1.86). The risk of
      infection was significantly higher in the 8 mg/kg combination group compared with
      controls (OR = 1.30; 95% CI 1.07, 1.58). No increased incidence of malignancy,
      tuberculosis reactivation or hepatitis was seen. CONCLUSION: Tocilizumab in
      combination with MTX as a treatment for RA is associated with a small but
      significantly increased risk of AEs, which is comparable with that of other
      biologics. Vigilance for untoward effects is, therefore, imperative in any
      patient treated with these immuno-suppressive agents.

PMID- 21078624
TI  - Comparison of an expanded ataxia interactome with patient medical records reveals
      a relationship between macular degeneration and ataxia.
AB  - Spinocerebellar ataxias 6 and 7 (SCA6 and SCA7) are neurodegenerative disorders
      caused by expansion of CAG repeats encoding polyglutamine (polyQ) tracts in
      CACNA1A, the alpha1A subunit of the P/Q-type calcium channel, and ataxin-7
      (ATXN7), a component of a chromatin-remodeling complex, respectively. We
      hypothesized that finding new protein partners for ATXN7 and CACNA1A would
      provide insight into the biology of their respective diseases and their
      relationship to other ataxia-causing proteins. We identified 118 protein
      interactions for CACNA1A and ATXN7 linking them to other ataxia-causing proteins
      and the ataxia network. To begin to understand the biological relevance of these
      protein interactions within the ataxia network, we used OMIM to identify diseases
      associated with the expanded ataxia network. We then used Medicare patient
      records to determine if any of these diseases co-occur with hereditary ataxia. We
      found that patients with ataxia are at 3.03-fold greater risk of these diseases
      than Medicare patients overall. One of the diseases comorbid with ataxia is
      macular degeneration (MD). The ataxia network is significantly (P= 7.37 * 10(-5))
      enriched for proteins that interact with known MD-causing proteins, forming a MD
      subnetwork. We found that at least two of the proteins in the MD subnetwork have
      altered expression in the retina of Ataxin-7(266Q/+) mice suggesting an in vivo
      functional relationship with ATXN7. Together these data reveal novel protein
      interactions and suggest potential pathways that can contribute to the
      pathophysiology of ataxia, MD, and diseases comorbid with ataxia.

PMID- 21078629
TI  - Hormonal replacement therapy does not affect self-estimated pain or experimental
      pain responses in post-menopausal women suffering from fibromyalgia: a double
      blind, randomized, placebo-controlled trial.
AB  - OBJECTIVES: FM is a condition that preferentially affects women. Sex hormones,
      and in particular oestrogens, have been shown to affect pain processing and pain
      sensitivity, and oestrogen deficit has been considered a potentially promoting
      factor for FM. However, the effects of oestrogen treatment in patients suffering
      from FM have not been studied. Here, we examined the effect of transdermal
      oestrogen substitution treatment on experimental as well as self-estimated pain
      in women suffering from FM. METHODS: Twenty-nine post-menopausal women were
      randomized to either 8 weeks of treatment with transdermal 17beta-oestradiol (50
      ug/day) or placebo according to a double-blind protocol. A self-estimation of
      pain, a set of quantitative sensory tests measuring thresholds to temperature,
      thermal pain, cold pain and pressure pain, and a cold pressor test were performed
      on three occasions: before treatment, after 8 weeks of treatment and 20 weeks
      after cessation of treatment. RESULTS: Hormonal replacement treatment
      significantly increased serum oestradiol levels as expected (P < 0.01). However,
      no differences in self-estimated pain were seen between treatment and placebo
      groups, nor were there any differences between the two groups regarding the
      results of the quantitative sensory tests or the cold pressor test at any of the
      examined time points. CONCLUSION: Eight weeks of transdermal oestradiol treatment
      does not influence perceived pain, pain thresholds or pain tolerance as compared
      with placebo treatment in post-menopausal women suffering from FM. TRIAL
      REGISTRATION: ClinicalTrials.gov Registration; http://www.clinicaltrials.gov;
      NCT01087593.

PMID- 21078630
TI  - Comparative efficacy and acceptability of amitriptyline, duloxetine and
      milnacipran in fibromyalgia syndrome: a systematic review with meta-analysis.
AB  - OBJECTIVES: To evaluate and compare the efficacy and acceptability of the
      antidepressants amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) for
      FM syndrome (FMS). METHODS: Cochrane Library, MEDLINE, SCOPUS,
      www.clinicalstudyresults.org and www.clinicalTrials.gov were searched for
      randomized pharmacological placebo-controlled trials until 30 May 2010. Outcomes
      of interest were symptom reduction [pain, fatigue, sleep disturbance and reduced
      health-related quality of life (HRQOL)] and acceptability (total drop-out rates).
      We performed a meta-analysis of each drug vs placebo using a random-effects model
      and adjusted indirect analyses of the three drugs. Methodological quality was
      assessed by the Cochrane risk of bias tool. RESULTS: Ten AMT studies (612
      patients), four DLX studies (1411 patients) and five MLN studies (4129 patients)
      met the inclusion criteria. The reported methodological quality of most AMT
      trials was poor, that of DLX and MLN were high. The three drugs were superior to
      placebo except DLX for fatigue, MLN for sleep disturbance and AMT for HRQOL. The
      significant effects of AMT and DLX were small and those of MLN not substantial.
      In adjusted indirect comparisons, AMT was superior to DLX and MLN in reduction of
      pain, sleep disturbances, fatigue and limitations of HRQOL. DLX was superior to
      MLN in reducing pain, sleep disturbances and limitations of HRQOL. MLN was
      superior to DLX in reducing fatigue. There were no significant differences in
      acceptability of the three drugs. CONCLUSIONS: AMT cannot be regarded as the gold
      standard of FMS therapy with antidepressants because of the methodological
      limitations of its trials.

PMID- 21078633
TI  - Complex dynamics of life at different scales: from genomic to global
      environmental issues.
AB  - This introduction to the Theme Issue, Complex dynamics of life at different
      scales: from genomic to global environmental issues, gives a short overview on
      why the ideas and concepts in complexity and nonlinearity are relevant to the
      understanding of life in its different manifestations. Also, it discusses how
      life phenomena can be thought of as composing different scales of organization.
      Finally, the articles in this thematic publication are briefly commented on in
      terms of their relevance in helping to understand the complexity of life systems.

PMID- 21078631
TI  - Transient accelerated junctional rhythm late after para-Hisian accessory pathway
      cryoablation: a new phenomenon.
AB  - Transient junctional rhythm late after para-Hisian accessory pathway cryoablation
      occurred in two patients. Cryoablation was delivered using the 8 mm tip Freezor
      MAXTM catheter (Cryocath Technologies Inc., Montreal, Canada), 2 mm distal to the
      largest His potential. Transient symptomatic junctional rhythm occurred after 1
      week. This benign, self-limiting rhythm is possibly caused by reversible
      cryoinjury to the His bundle periphery.

PMID- 21078634
TI  - Error catastrophe for viruses infecting cells: analysis of the phase transition
      in terms of error classes.
AB  - RNA viruses offer a very exciting arena in which to study evolution in 'real
      time' owing to both their high replication rate-many generations per day are
      possible-and their high mutation rate, leading to a large phenotypic variety.
      They can be regarded as a swarm of genetically related mutants around a dominant
      or master genetic sequence. This system is called a 'viral quasi-species'. Thus,
      a common framework to describe RNA viral dynamics is by means of the quasi
      species equation (QSE). The QSE is in fact a system of a very large number of
      nonlinear coupled equations. Here, we consider a simpler formulation in terms of
      'error classes', which groups all the sequences differing from the master
      sequence by the same number of genomic differences into one population class.
      From this, based on the analogies with Bose condensation, we use thermodynamic
      inspired observables to analyse and characterize the 'phase transition' through
      the so-called 'RNA virus error catastrophe'.

PMID- 21078635
TI  - Living on the edge of chaos: minimally nonlinear models of genetic regulatory
      dynamics.
AB  - Linearized catalytic reaction equations (modelling, for example, the dynamics of
      genetic regulatory networks), under the constraint that expression levels, i.e.
      molecular concentrations of nucleic material, are positive, exhibit non-trivial
      dynamical properties, which depend on the average connectivity of the reaction
      network. In these systems, an inflation of the edge of chaos and multi-stability
      have been demonstrated to exist. The positivity constraint introduces a
      nonlinearity, which makes chaotic dynamics possible. Despite the simplicity of
      such minimally nonlinear systems, their basic properties allow us to understand
      the fundamental dynamical properties of complex biological reaction networks. We
      analyse the Lyapunov spectrum, determine the probability of finding stationary
      oscillating solutions, demonstrate the effect of the nonlinearity on the
      effective in- and out-degree of the active interaction network, and study how the
      frequency distributions of oscillatory modes of such a system depend on the
      average connectivity.

PMID- 21078636
TI  - Observable effects of Ca2+ buffers on local Ca2+ signals.
AB  - Calcium signals participate in a large variety of physiological processes. In
      many instances, they involve calcium entry through inositol 1,4,5-trisphosphate
      (IP(3)) receptors (IP(3)Rs), which are usually organized in clusters. Recent high
      resolution optical experiments by Smith & Parker have provided new information on
      Ca(2+) release from clustered IP(3)Rs. In the present paper, we use the model
      recently introduced by Solovey & Ponce Dawson to determine how the distribution
      of the number of IP(3)Rs that become open during a localized release event may
      change by the presence of Ca(2+) buffers, substances that react with Ca(2+),
      altering its concentration and transport properties. We then discuss how buffer
      properties could be extracted from the observation of local signals.

PMID- 21078637
TI  - Fractal structures in stenoses and aneurysms in blood vessels.
AB  - Recent advances in the field of chaotic advection provide the impetus to revisit
      the dynamics of particles transported by blood flow in the presence of vessel
      wall irregularities. The irregularity, being either a narrowing or expansion of
      the vessel, mimicking stenoses or aneurysms, generates abnormal flow patterns
      that lead to a peculiar filamentary distribution of advected particles, which, in
      the blood, would include platelets. Using a simple model, we show how the
      filamentary distribution depends on the size of the vessel wall irregularity, and
      how it varies under resting or exercise conditions. The particles transported by
      blood flow that spend a long time around a disturbance either stick to the vessel
      wall or reside on fractal filaments. We show that the faster flow associated with
      exercise creates widespread filaments where particles can get trapped for a
      longer time, thus allowing for the possible activation of such particles. We
      argue, based on previous results in the field of active processes in flows, that
      the non-trivial long-time distribution of transported particles has the potential
      to have major effects on biochemical processes occurring in blood flow, including
      the activation and deposition of platelets. One aspect of the generality of our
      approach is that it also applies to other relevant biological processes, an
      example being the coexistence of plankton species investigated previously.

PMID- 21078638
TI  - The constructive role of diversity in the global response of coupled neuron
      systems.
AB  - We study the effect that the heterogeneity present among the elements of an
      ensemble of coupled excitable neurons has on the collective response of the
      system to an external signal. We consider two different interaction scenarios,
      one in which the neurons are diffusively coupled and another in which the neurons
      interact via pulse-like signals. We find that the type of interaction between the
      neurons has a crucial role in determining the response of the system to the
      external modulation. We develop a mean-field theory based on an order parameter
      expansion that quantitatively reproduces the numerical results in the case of
      diffusive coupling.

PMID- 21078639
TI  - Modelling hierarchical structure in functional brain networks.
AB  - In this work, we focus on a complex-network approach for the study of the brain.
      In particular, we consider functional brain networks, where the vertices
      represent different anatomical regions and the links their functional
      connectivity. First, we build these networks using data obtained with functional
      magnetic resonance imaging. Then, we analyse the main characteristics of these
      complex networks, including degree distribution, the presence of modules and
      hierarchical structure. Finally, we present a network model with dynamical nodes
      and adaptive links. We show that the model allows for the emergence of complex
      networks with characteristics similar to those observed in functional brain
      networks.

PMID- 21078640
TI  - Modelling the mobility of living organisms in heterogeneous landscapes: does
      memory improve foraging success?
AB  - Thanks to recent technological advances, it is now possible to track with an
      unprecedented precision and for long periods of time the movement patterns of
      many living organisms in their habitat. The increasing amount of data available
      on single trajectories offers the possibility of understanding how animals move
      and of testing basic movement models. Random walks have long represented the main
      description for micro-organisms and have also been useful to understand the
      foraging behaviour of large animals. Nevertheless, most vertebrates, in
      particular humans and other primates, rely on sophisticated cognitive tools such
      as spatial maps, episodic memory and travel cost discounting. These properties
      call for other modelling approaches of mobility patterns. We propose a foraging
      framework where a learning mobile agent uses a combination of memory-based and
      random steps. We investigate how advantageous it is to use memory for exploiting
      resources in heterogeneous and changing environments. An adequate balance of
      determinism and random exploration is found to maximize the foraging efficiency
      and to generate trajectories with an intricate spatio-temporal order, where
      travel routes emerge without multi-step planning. Based on this approach, we
      propose some tools for analysing the non-random nature of mobility patterns in
      general.

PMID- 21078641
TI  - Home range evolution and its implication in population outbreaks.
AB  - We investigated the phenomenon of population outbreaks in a spatial predator-prey
      model, and we found that pattern formation and outbreaks occur if the predators
      have a limited neighbourhood of interaction with the preys. The outbreaks can
      display a scale-invariant power-law tail, indicating self-organized criticality.
      We have also studied the system from an evolutionary point of view, where the
      predator home range is a hereditary trait subjected to mutations. We found that
      mutation drives the predator home range area to an optimal value where pattern
      formation and outbreaks are still present, but the latter are much less frequent.
      We developed analytical approximations using mean field and pair correlation
      techniques that indicate that the predation strategy is crucial for existence of
      this optimal home range area.

PMID- 21078642
TI  - Modelling the dynamics of dengue real epidemics.
AB  - In this work, we use a mathematical model for dengue transmission with the aim of
      analysing and comparing two dengue epidemics that occurred in Salvador, Brazil,
      in 1995-1996 and 2002. Using real data, we obtain the force of infection, Lambda,
      and the basic reproductive number, R(0), for both epidemics. We also obtain the
      time evolution of the effective reproduction number, R(t), which results in a
      very suitable measure to compare the patterns of both epidemics. Based on the
      analysis of the behaviour of R(0) and R(t) in relation to the adult mosquito
      control parameter of the model, we show that the control applied only to the
      adult stage of the mosquito population is not sufficient to stop dengue
      transmission, emphasizing the importance of applying the control to the aquatic
      phase of the mosquito.

PMID- 21078643
TI  - A model for the emergence of geopolitical division.
AB  - In this work, we present a model based on a competitive dynamics that intends to
      imitate the processes leading to some characteristics of the geopolitical
      division. The model departs from very simple principles of geopolitical theory
      and geometrical considerations, but succeeds in explaining the general features
      related to the actual process. At the same time, we will propose an evolutionary
      explanation to the fact that most capitals (in Eurasia) are located far from the
      borders or coasts and, in many cases, close to the barycentre of the respective
      countries.

PMID- 21078644
TI  - Complex dynamics of our economic life on different scales: insights from search
      engine query data.
AB  - Search engine query data deliver insight into the behaviour of individuals who
      are the smallest possible scale of our economic life. Individuals are submitting
      several hundred million search engine queries around the world each day. We study
      weekly search volume data for various search terms from 2004 to 2010 that are
      offered by the search engine Google for scientific use, providing information
      about our economic life on an aggregated collective level. We ask the question
      whether there is a link between search volume data and financial market
      fluctuations on a weekly time scale. Both collective 'swarm intelligence' of
      Internet users and the group of financial market participants can be regarded as
      a complex system of many interacting subunits that react quickly to external
      changes. We find clear evidence that weekly transaction volumes of S&P 500
      companies are correlated with weekly search volume of corresponding company
      names. Furthermore, we apply a recently introduced method for quantifying complex
      correlations in time series with which we find a clear tendency that search
      volume time series and transaction volume time series show recurring patterns.

PMID- 21078645
TI  - Time-asymmetric fluctuations in the atmosphere: daily mean temperatures and total
      column ozone.
AB  - Fluctuations breaking time-reversal symmetry are common attributes of dissipative
      systems operating far from equilibrium. Recent developments in non-equilibrium
      statistical physics represent a significant step towards an understanding of how
      time-reversible microscopic laws can yield to inherent irreversibility on meso-
      or macroscopic scales. Most of the theoretical conclusions consider quantities
      (e.g. entropy production) that are difficult to obtain with an appropriate
      accuracy in real systems. Probably less-complicated measures, such as the simple
      step-number ratio used in this work, can also help to characterize time
      asymmetric fluctuations. In the first part, we give a short summary of recent
      results on asymmetric daily mean temperature changes. The second part discusses
      total-column ozone fluctuations, where statistically significant asymmetries are
      also detected. A detailed correlation analysis of ozone signals and high-altitude
      temperature records supports the strong coupling between tropospheric dynamics
      and stratospheric processes on synoptic time scales.

PMID- 21078646
TI  - Evolutionary and ecological approaches to the study of personality.
AB  - This introduction to the themed issue on Evolutionary and ecological approaches
      to the study of personality provides an overview of conceptual, theoretical and
      methodological progress in research on animal personalities over the last decade,
      and places the contributions to this volume in context. The issue has three main
      goals. First, we aimed to bring together theoreticians to contribute to the
      development of models providing adaptive explanations for animal personality that
      could guide empiricists, and stimulate exchange of ideas between the two groups
      of researchers. Second, we aimed to stimulate cross-fertilization between
      different scientific fields that study personality, namely behavioural ecology,
      psychology, genomics, quantitative genetics, neuroendocrinology and developmental
      biology. Third, we aimed to foster the application of an evolutionary framework
      to the study of personality.

PMID- 21078647
TI  - Recent models for adaptive personality differences: a review.
AB  - In this paper we review recent models that provide adaptive explanations for
      animal personalities: individual differences in behaviour (or suites of
      correlated behaviours) that are consistent over time or contexts. We start by
      briefly discussing patterns of variation in behaviour that have been documented
      in natural populations. In the main part of the paper we discuss models for
      personality differences that (i) explain animal personalities as adaptive
      behavioural responses to differences in state, (ii) investigate how feedbacks
      between state and behaviour can stabilize initial differences among individuals
      and (iii) provide adaptive explanations for animal personalities that are not
      based on state differences. Throughout, we focus on two basic questions. First,
      what is the basic conceptual idea underlying the model? Second, what are the key
      assumptions and predictions of the model? We conclude by discussing empirical
      features of personalities that have not yet been addressed by formal modelling.
      While this paper is primarily intended to guide empiricists through current
      adaptive theory, thereby stimulating empirical tests of these models, we hope it
      also inspires theoreticians to address aspects of personalities that have
      received little attention up to now.

PMID- 21078648
TI  - An explanatory framework for adaptive personality differences.
AB  - We develop a conceptual framework for the understanding of animal personalities
      in terms of adaptive evolution. We focus on two basic questions. First, why do
      behavioural types exhibit limited behavioural plasticity, that is, behavioural
      correlations both across contexts and over time? Second, how can multiple
      behavioural types coexist within a single population? We emphasize differences in
      'state' among individuals in combination with state-dependent behaviour. Some
      states are inherently stable and individual differences in such states can
      explain stable differences in suites of behaviour if it is adaptive to make
      behaviour in various contexts dependent on such states. Behavioural stability and
      cross-context correlations in behaviour are more difficult to explain if
      individual states are potentially more variable. In such cases stable
      personalities can result from state-dependent behaviour if state and behaviour
      mutually reinforce each other by feedback mechanisms. We discuss various
      evolutionary mechanisms for the maintenance of variation (in states and/or
      behaviour), including frequency-dependent selection, spatial variation with
      incomplete matching between habitat and phenotype, bet-hedging in a temporally
      fluctuating environment, and non-equilibrium dynamics. Although state differences
      are important, we also discuss how social conventions and social signalling can
      give rise to adaptive personality differences in the absence of state
      differences.

PMID- 21078649
TI  - Evolutionary models of metabolism, behaviour and personality.
AB  - I explore the relationship between metabolism and personality by establishing how
      selection acts on metabolic rate and risk-taking in the context of a trade-off
      between energy and predation. Using a simple time budget model, I show that a
      high resting metabolic rate is not necessarily associated with a high daily
      energy expenditure. The metabolic rate that minimizes the time spent foraging
      does not maximize the net gain rate while foraging, and it is not always
      advantageous for animals to have a higher metabolic rate when food availability
      is high. A model based on minimizing the ratio of mortality rate to net gain rate
      is used to determine how a willingness to take risks should be correlated with
      metabolic rate. My results establish that it is not always advantageous for
      animals to take greater risks when metabolic rate is high. When foraging
      intensity and metabolic rate coevolve, I show that in a particular case different
      combinations of foraging intensity and metabolic rate can have equal fitness.

PMID- 21078650
TI  - Risk, resources and state-dependent adaptive behavioural syndromes.
AB  - Many animals exhibit behavioural syndromes-consistent individual differences in
      behaviour across two or more contexts or situations. Here, we present adaptive,
      state-dependent mathematical models for analysing issues about behavioural
      syndromes. We find that asset protection (where individuals with more 'assets'
      tend be more cautious) and starvation avoidance, two state-dependent mechanisms,
      can explain short-term behavioural consistency, but not long-term stable
      behavioural types (BTs). These negative-feedback mechanisms tend to produce
      convergence in state and behaviour over time. In contrast, a positive-feedback
      mechanism, state-dependent safety (where individuals with higher energy reserves,
      size, condition or vigour are better at coping with predators), can explain
      stable differences in personality over the long term. The relative importance of
      negative- and positive-feedback mechanisms in governing behavioural consistency
      depends on environmental conditions (predation risk and resource availability).
      Behavioural syndromes emerge more readily in conditions of intermediate
      ecological favourability (e.g. medium risk and medium resources, or high risk and
      resources, or low risk and resources). Under these conditions, individuals with
      higher initial state maintain a tendency to be bolder than individuals that start
      with low initial state; i.e. later BT is determined by state during an early
      'developmental window'. In contrast, when conditions are highly favourable (low
      risk, high resources) or highly unfavourable (high risk, low resources),
      individuals converge to be all relatively bold or all relatively cautious,
      respectively. In those circumstances, initial differences in BT are not
      maintained over the long term, and there is no early developmental window where
      initial state governs later BT. The exact range of ecological conditions
      favouring behavioural syndromes depends also on the strength of state-dependent
      safety.

PMID- 21078651
TI  - Evolutionary genomics of animal personality.
AB  - Research on animal personality can be approached from both a phenotypic and a
      genetic perspective. While using a phenotypic approach one can measure present
      selection on personality traits and their combinations. However, this approach
      cannot reconstruct the historical trajectory that was taken by evolution.
      Therefore, it is essential for our understanding of the causes and consequences
      of personality diversity to link phenotypic variation in personality traits with
      polymorphisms in genomic regions that code for this trait variation. Identifying
      genes or genome regions that underlie personality traits will open exciting
      possibilities to study natural selection at the molecular level, gene-gene and
      gene-environment interactions, pleiotropic effects and how gene expression shapes
      personality phenotypes. In this paper, we will discuss how genome information
      revealed by already established approaches and some more recent techniques such
      as high-throughput sequencing of genomic regions in a large number of individuals
      can be used to infer micro-evolutionary processes, historical selection and
      finally the maintenance of personality trait variation. We will do this by
      reviewing recent advances in molecular genetics of animal personality, but will
      also use advanced human personality studies as case studies of how molecular
      information may be used in animal personality research in the near future.

PMID- 21078652
TI  - What can whole genome expression data tell us about the ecology and evolution of
      personality?
AB  - Consistent individual differences in behaviour, aka personality, pose several
      evolutionary questions. For example, it is difficult to explain within-individual
      consistency in behaviour because behavioural plasticity is often advantageous. In
      addition, selection erodes heritable behavioural variation that is related to
      fitness, therefore we wish to know the mechanisms that can maintain between
      individual variation in behaviour. In this paper, we argue that whole genome
      expression data can reveal new insights into the proximate mechanisms underlying
      personality, as well as its evolutionary consequences. After introducing the
      basics of whole genome expression analysis, we show how whole genome expression
      data can be used to understand whether behaviours in different contexts are
      affected by the same molecular mechanisms. We suggest strategies for using the
      power of genomics to understand what maintains behavioural variation, to study
      the evolution of behavioural correlations and to compare personality traits
      across diverse organisms.

PMID- 21078653
TI  - Applying a quantitative genetics framework to behavioural syndrome research.
AB  - Current interest in behavioural syndromes, or 'animal personalities', reinforces
      a need for behavioural ecologists to adopt a multivariate view of phenotypes.
      Fortunately, many of the methodological and theoretical issues currently being
      dealt with by behavioural ecologists within the context of behavioural syndromes
      have previously been investigated by researchers in other areas of evolutionary
      ecology. As a result of these previous efforts, behavioural syndrome researchers
      have considerable theory and a wide range of tools already available to them.
      Here, we discuss aspects of quantitative genetics useful for understanding the
      multivariate phenotype as well as the relevance of quantitative genetics to
      behavioural syndrome research. These methods not only allow the proper
      characterization of the multivariate behavioural phenotype and genotype-including
      behaviours within, among and independent of behavioural syndrome structures-but
      also allow predictions as to how populations may respond to selection on
      behaviours within syndromes. An application of a quantitative genetics framework
      to behavioural syndrome research also clarifies and refines the questions that
      should be asked.

PMID- 21078654
TI  - Coping styles and behavioural flexibility: towards underlying mechanisms.
AB  - A coping style (also termed behavioural syndrome or personality) is defined as a
      correlated set of individual behavioural and physiological characteristics that
      is consistent over time and across situations. This relatively stable trait is a
      fundamental and adaptively significant phenomenon in the biology of a broad range
      of species, i.e. it confers differential fitness consequences under divergent
      environmental conditions. Behavioural flexibility appears to be an important
      underlying attribute or feature of the coping style that might explain
      consistency across situations. Proactive coping is characterized by low
      flexibility expressed as rather rigid, routine-like behavioural tendencies and
      reduced impulse control (behavioural inhibition) in operant conditioning
      paradigms. This article summarizes some of the evidence that individual
      differentiation in behavioural flexibility emerges as a function of underlying
      variability in the activation of a brain circuitry that includes the prefrontal
      cortex and its key neurochemical signalling pathways (e.g. dopaminergic and
      serotonergic input). We argue that the multidimensional nature of animal
      personality and the terminology used for the various dimensions should reflect
      the differential pattern of activation of the underlying neuronal network and the
      behavioural control function of its components. Accordingly, unravelling the
      molecular mechanisms that give rise to individual differences in the coping style
      will be an important topic in biobehavioural neurosciences, ecology and
      evolutionary biology.

PMID- 21078655
TI  - Developmental perspectives on personality: implications for ecological and
      evolutionary studies of individual differences.
AB  - Developmental processes can have major impacts on the correlations in behaviour
      across contexts (contextual generality) and across time (temporal consistency)
      that are the hallmarks of animal personality. Personality can and does change: at
      any given age or life stage it is contingent upon a wide range of experiential
      factors that occurred earlier in life, from prior to conception through
      adulthood. We show how developmental reaction norms that describe the effects of
      prior experience on a given behaviour can be used to determine whether the
      effects of a given experience at a given age will affect contextual generality at
      a later age, and to illustrate how variation within individuals in developmental
      plasticity leads to variation in contextual generality across individuals as a
      function of experience. We also show why niche-picking and niche-construction,
      behavioural processes which allow individuals to affect their own developmental
      environment, can affect the contextual generality and the temporal consistency of
      personality. We conclude by discussing how an appreciation of developmental
      processes can alert behavioural ecologists studying animal personality to
      critical, untested assumptions that underlie their own research programmes, and
      outline situations in which a developmental perspective can improve studies of
      the functional significance and evolution of animal personality.

PMID- 21078656
TI  - Personality: bridging the literatures from human psychology and behavioural
      ecology.
AB  - The concept of personality has recently begun to attract a great deal of interest
      in behavioural ecology. However, there is also a large and mature literature on
      personality within human psychology. These two bodies of work have developed
      independently and at present make rather little reference to one another. The
      current paper has two main objectives. First, we seek to acquaint behavioural
      ecologists with the principal ideas and issues found in the human personality
      psychology literature. Second, we explore how ideas from the behavioural ecology
      literature might help advance research in human personality psychology. We
      suggest strong potential for convergence between the two literatures in the near
      future. Common themes of this future unified science of personality include the
      conception of personality traits as reaction norms, a commitment to the
      importance of direct measurement of behaviour, investigation of both proximate
      and ultimate explanations for personality variation, and a concern with the
      impact of personality variation on survival and reproductive success.

PMID- 21078657
TI  - Personality and the emergence of the pace-of-life syndrome concept at the
      population level.
AB  - The pace-of-life syndrome (POLS) hypothesis specifies that closely related
      species or populations experiencing different ecological conditions should differ
      in a suite of metabolic, hormonal and immunity traits that have coevolved with
      the life-history particularities related to these conditions. Surprisingly, two
      important dimensions of the POLS concept have been neglected: (i) despite
      increasing evidence for numerous connections between behavioural, physiological
      and life-history traits, behaviours have rarely been considered in the POLS yet;
      (ii) the POLS could easily be applied to the study of covariation among traits
      between individuals within a population. In this paper, we propose that
      consistent behavioural differences among individuals, or personality, covary with
      life history and physiological differences at the within-population,
      interpopulation and interspecific levels. We discuss how the POLS provides a
      heuristic framework in which personality studies can be integrated to address how
      variation in personality traits is maintained within populations.

PMID- 21078658
TI  - Personality-dependent dispersal: characterization, ontogeny and consequences for
      spatially structured populations.
AB  - Dispersal is one of the most fundamental components of ecology, and affects
      processes as diverse as population growth, metapopulation dynamics, gene flow and
      adaptation. Although the act of moving from one habitat to another entails major
      costs to the disperser, empirical and theoretical studies suggest that these
      costs can be reduced by having morphological, physiological or behavioural
      specializations for dispersal. A few recent studies on different systems showed
      that individuals exhibit personality-dependent dispersal, meaning that dispersal
      tendency is associated with boldness, sociability or aggressiveness. Indeed, in
      several species, dispersers not only develop behavioural differences at the onset
      of dispersal, but display these behavioural characteristics through their life
      cycle. While personality-dependent dispersal has been demonstrated in only a few
      species, we believe that it is a widespread phenomenon with important ecological
      consequences. Here, we review the evidence for behavioural differences between
      dispersers and residents, to what extent they constitute personalities. We also
      examine how a link between personality traits and dispersal behaviours can be
      produced and how personality-dependent dispersal affects the dynamics of
      metapopulations and biological invasions. Finally, we suggest future research
      directions for population biologists, behavioural ecologists and conservation
      biologists such as how the direction and the strength of the relationship between
      personality traits and dispersal vary with ecological contexts.

PMID- 21078660
TI  - The building-up of social relationships: behavioural types, social networks and
      cooperative breeding in a cichlid.
AB  - Consistent individual differences in behavioural types may not only cause
      variation in life-history decisions, but may also affect the choice of social
      partners and sociality in general. Here, we tested whether and how behavioural
      type influences the establishment of social ties using the cooperatively breeding
      cichlid, Neolamprologus pulcher. In a habitat saturation experiment with
      individuals pre-tested for behavioural type, we first analysed whether
      behavioural type affected the likelihood of settlement (i.e. social status),
      group sizes, and the types of dominant and subordinate individuals accepted as
      group members. Corrected for effects of body size and sex, the behavioural type
      did not affect settlement. However, bold dominant males only accepted smaller
      females, and grouped with bold subordinates, while shy dominant males accepted
      larger females than themselves, and grouped with shy subordinates. Second, we
      analysed the relationships between behavioural type and the aggressiveness or
      affiliation social network. Behavioural type significantly affected the number
      and quality of connections within the two networks. We show that behavioural
      types affect group composition, social networks and status achieved, in
      interaction with body size. Thus, the interactions within groups may depend not
      only on age, size and sex, but also on the behavioural type of the individuals
      involved.

PMID- 21078659
TI  - Parasitism and the evolutionary ecology of animal personality.
AB  - The ecological factors responsible for the evolution of individual differences in
      animal personality (consistent individual differences in the same behaviour
      across time and contexts) are currently the subject of intense debate. A limited
      number of ecological factors have been investigated to date, with most attention
      focusing on the roles of resource competition and predation. We suggest here that
      parasitism may play a potentially important, but largely overlooked, role in the
      evolution of animal personalities. We identify two major routes by which
      parasites might influence the evolution of animal personality. First, because the
      risk of acquiring parasites can be influenced by an individual's behavioural
      type, local parasite regimes may impose selection on personality traits and
      behavioural syndromes (correlations between personality traits). Second, because
      parasite infections have consequences for aspects of host 'state', parasites
      might induce the evolution of individual differences in certain types of host
      behaviour in populations with endemic infections. Also, because infection often
      leads to specific changes in axes of personality, parasite infections have the
      potential to decouple behavioural syndromes. Host-parasite systems therefore
      provide researchers with valuable tools to study personality variation and
      behavioural syndromes from a proximate and ultimate perspective.

PMID- 21078661
TI  - Personality in the context of social networks.
AB  - There is great interest in environmental effects on the development and evolution
      of animal personality traits. An important component of an individual's
      environment is its social environment. However, few studies look beyond dyadic
      relationships and try to place the personality of individuals in the context of a
      social network. Social network analysis provides us with many new metrics to
      characterize the social fine-structure of populations and, therefore, with an
      opportunity to gain an understanding of the role that different personalities
      play in groups, communities and populations regarding information or disease
      transmission or in terms of cooperation and policing of social conflicts. The
      network position of an individual is largely a consequence of its interactive
      strategies. However, the network position can also shape an individual's
      experiences (especially in the case of juveniles) and therefore can influence the
      way in which it interacts with others in future. Finally, over evolutionary time,
      the social fine-structure of animal populations (as quantified by social network
      analysis) can have important consequences for the evolution of personalities-an
      approach that goes beyond the conventional game-theoretic analyses that assumed
      random mixing of individuals in populations.

PMID- 21078662
TI  - Histone deacetylase 9 activates gamma-globin gene expression in primary erythroid
      cells.
AB  - Strategies to induce fetal hemoglobin (HbF) synthesis for the treatment of beta
      hemoglobinopathies probably involve protein modifications by histone deacetylases
      (HDACs) that mediate gamma-globin gene regulation. However, the role of
      individual HDACs in globin gene expression is not very well understood; thus, the
      focus of our study was to identify HDACs involved in gamma-globin activation.
      K562 erythroleukemia cells treated with the HbF inducers hemin, trichostatin A,
      and sodium butyrate had significantly reduced mRNA levels of HDAC9 and its splice
      variant histone deacetylase-related protein. Subsequently, HDAC9 gene knockdown
      produced dose-dependent gamma-globin gene silencing over an 80-320 nm range.
      Enforced expression with the pTarget-HDAC9 vector produced a dose-dependent 2.5
      fold increase in gamma-globin mRNA (p < 0.05). Furthermore, ChIP assays showed
      HDAC9 binding in vivo in the upstream Ggamma-globin gene promoter region. To
      determine the physiological relevance of these findings, human primary erythroid
      progenitors were treated with HDAC9 siRNA; we observed 40 and 60% gamma-globin
      gene silencing in day 11 (early) and day 28 (late) progenitors. Moreover,
      enforced HDAC9 expression increased gamma-globin mRNA levels by 2.5-fold with a
      simultaneous 7-fold increase in HbF. Collectively, these data support a positive
      role for HDAC9 in gamma-globin gene regulation.

PMID- 21078664
TI  - Nimbolide sensitizes human colon cancer cells to TRAIL through reactive oxygen
      species- and ERK-dependent up-regulation of death receptors, p53, and Bax.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) shows promise as a cancer
      treatment, but acquired tumor resistance to TRAIL is a roadblock. Here we
      investigated whether nimbolide, a limonoid, could sensitize human colon cancer
      cells to TRAIL. As indicated by assays that measure esterase activity, sub-G(1)
      fractions, mitochondrial activity, and activation of caspases, nimbolide
      potentiated the effect of TRAIL. This limonoid also enhanced expression of death
      receptors (DRs) DR5 and DR4 in cancer cells. Gene silencing of the receptors
      reduced the effect of limonoid on TRAIL-induced apoptosis. Using pharmacological
      inhibitors, we found that activation of ERK and p38 MAPK was required for DR up
      regulation by nimbolide. Gene silencing of ERK abolished the enhancement of TRAIL
      induced apoptosis. Moreover, our studies indicate that the limonoid induced
      reactive oxygen species production, which was required for ERK activation, up
      regulation of DRs, and sensitization to TRAIL; these effects were mimicked by
      H(2)O(2). In addition, nimbolide down-regulated cell survival proteins, including
      I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-linked inhibitor of
      apoptosis protein, and up-regulated the pro-apoptotic proteins p53 and Bax.
      Interestingly, p53 and Bax up-regulation by nimbolide was required for
      sensitization to TRAIL but not for DR up-regulation. Overall, our results
      indicate that nimbolide can sensitize colon cancer cells to TRAIL-induced
      apoptosis through three distinct mechanisms: reactive oxygen species- and ERK
      mediated up-regulation of DR5 and DR4, down-regulation of cell survival proteins,
      and up-regulation of p53 and Bax.

PMID- 21078663
TI  - NFAT and IRF proteins regulate transcription of the anti-HIV gene, APOBEC3G.
AB  - The human cytidine deaminase APOBEC3G (A3G) is an innate restriction factor that
      inhibits human immunodeficiency virus, type 1 (HIV-1) replication. Regulation of
      A3G gene expression plays an important role in this suppression. Currently, an
      understanding of the mechanism of this gene regulation is largely unknown. Here,
      we have identified and characterized a TATA-less core promoter with an NFAT/IRF-4
      composite binding site that confers cell type-specific transcriptional
      regulation. We found that A3G expression is critically dependent on NFATc1/NFATc2
      and IRF-4. When either NFATc1 or NFATc2 and IRF-4 were co-expressed, A3G promoter
      activity was observed in cells that normally lack A3G expression and expression
      was not detected in the presence of the individual factors. This induced A3G
      expression allowed normally permissive CEMss cells to adopt a nonpermissive
      state, able to resist an HIV-1Deltavif challenge. This represents the first
      reporting of manipulating the restrictive state of a cell type via gene
      regulation. Identification of NFAT and IRF family members as critical regulators
      of A3G expression offers important insight into the transcriptional control
      mechanisms that regulate innate immune responses and identifies specific targets
      for therapeutic intervention aimed at effectively boosting our natural immunity,
      in the form of a host defensive factor, against HIV-1.

PMID- 21078666
TI  - The actin-binding protein, actinin alpha 4 (ACTN4), is a nuclear receptor
      coactivator that promotes proliferation of MCF-7 breast cancer cells.
AB  - Alpha actinins (ACTNs) are known for their ability to modulate cytoskeletal
      organization and cell motility by cross-linking actin filaments. We show here
      that ACTN4 harbors a functional LXXLL receptor interaction motif, interacts with
      nuclear receptors in vitro and in mammalian cells, and potently activates
      transcription mediated by nuclear receptors. Whereas overexpression of ACTN4
      potentiates estrogen receptor alpha (ERalpha)-mediated transcription in transient
      transfection reporter assays, knockdown of ACTN4 decreases it. In contrast,
      histone deacetylase 7 (HDAC7) inhibits estrogen receptor alpha (ERalpha)-mediated
      transcription. Moreover, the ACTN4 mutant lacking the CaM (calmodulin)-like
      domain that is required for its interaction with HDAC7 fails to activate
      transcription by ERalpha. Chromatin immunoprecipitation (ChIP) assays demonstrate
      that maximal associations of ACTN4 and HDAC7 with the pS2 promoter are mutually
      exclusive. Knockdown of ACTN4 significantly decreases the expression of ERalpha
      target genes including pS2 and PR and also affects cell proliferation of MCF-7
      breast cancer cells with or without hormone, whereas knockdown of HDAC7 exhibits
      opposite effects. Interestingly, overexpression of wild-type ACTN4, but not the
      mutants defective in interacting with ERalpha or HDAC7, results in an increase in
      pS2 and PR mRNA accumulation in a hormone-dependent manner. In summary, we have
      identified ACTN4 as a novel, atypical coactivator that regulates transcription
      networks to control cell growth.

PMID- 21078665
TI  - A small ribosomal subunit (SSU) processome component, the human U3 protein 14A
      (hUTP14A) binds p53 and promotes p53 degradation.
AB  - Ribosome biogenesis is required for normal cell function, and aberrant ribosome
      biogenesis can lead to p53 activation. However, how p53 is activated by defects
      of ribosome biogenesis remains to be determined. Here, we identified human UTP14a
      as an SSU processome component by showing that hUTP14a is nucleolar, associated
      with U3 snoRNA and involved in 18 S rRNA processing. Interestingly, ectopic
      expression of hUTP14a resulted in a decrease and knockdown of hUTP14a led to an
      increase of p53 protein levels. We showed that hUTP14a physically interacts with
      p53 and functionally promotes p53 turn-over, and that hUTP14a promotion of p53
      destabilization is sensitive to a proteasome inhibitor but independent of
      ubiquitination. Significantly, knockdown of hUTP14a led to cell cycle arrest and
      apoptosis. Our data identified a novel pathway for p53 activation through a
      defect in rRNA processing and suggest that a ribosome biogenesis factor itself
      could act as a sensor for nucleolar stress to regulate p53.

PMID- 21078668
TI  - Identification of residues within tropomodulin-1 responsible for its localization
      at the pointed ends of the actin filaments in cardiac myocytes.
AB  - Tropomodulin is a tropomyosin-dependent actin filament capping protein involved
      in the structural formation of thin filaments and in the regulation of their
      lengths through its localization at the pointed ends of actin filaments. The
      disordered N-terminal domain of tropomodulin contains three functional sites: two
      tropomyosin-binding and one tropomyosin-dependent actin-capping sites. The C
      terminal half of tropomodulin consists of one compact domain containing a
      tropomyosin-independent actin-capping site. Here we determined the structural
      properties of tropomodulin-1 that affect its roles in cardiomyocytes. To explore
      the significance of individual tropomyosin-binding sites, GFP-tropomodulin-1 with
      single mutations that destroy each tropomyosin-binding site was expressed in
      cardiomyocytes. We demonstrated that both sites are necessary for the optimal
      localization of tropomodulin-1 at thin filament pointed ends, with site 2 acting
      as the major determinant. To investigate the functional properties of the
      tropomodulin C-terminal domain, truncated versions of GFP-tropomodulin-1 were
      expressed in cardiomyocytes. We discovered that the leucine-rich repeat (LRR)
      fold and the C-terminal helix are required for its proper targeting to the
      pointed ends. To investigate the structural significance of the LRR fold, we
      generated three mutations within the C-terminal domain (V232D, F263D, and L313D).
      Our results show that these mutations affect both tropomyosin-independent actin
      capping activity and pointed end localization, most likely by changing local
      conformations of either loops or side chains of the surfaces involved in the
      interactions of the LRR domain. Studying the influence of these mutations
      individually, we concluded that, in addition to the tropomyosin-independent actin
      capping site, there appears to be another regulatory site within the tropomodulin
      C-terminal domain.

PMID- 21078667
TI  - Converting the highly amyloidogenic human calcitonin into a powerful fibril
      inhibitor by three-dimensional structure homology with a non-amyloidogenic
      analogue.
AB  - Irreversible aggregation limits bioavailability and therapeutic activity of
      protein-based drugs. Here we show that an aggregation-resistant mutant can be
      engineered by structural homology with a non-amyloidogenic analogue and that the
      aggregation-resistant variant may act as an inhibitor. This strategy has
      successfully been applied to the amyloidogenic human calcitonin (hCT). Including
      only five residues from the non-amyloidogenic salmon calcitonin (sCT), we
      obtained a variant, polar human calcitonin (phCT), whose solution structure was
      shown by CD, NMR, and calculations to be practically identical to that of sCT.
      phCT was also observed to be a potent amyloidogenesis inhibitor of hCT when mixed
      with it in a 1:1 ratio. Fibrillation studies of phCT and the phCT-hCT mixture
      mimicked the sCT behavior in the kinetics and shapes of the fibrils with a
      dramatic reduction with respect to hCT. Finally, the effect of phCT alone and of
      the mixture on the intracellular cAMP level in T47D cells confirmed for the
      mutant and the mixture their calcitonin-like activity, exhibiting stimulation
      effects identical to those of sCT, the current therapeutic form. The strategy
      followed appears to be suitable to develop new forms of hCT with a striking
      reduction of aggregation and improved activity. Finally, the inhibitory
      properties of the aggregation-resistant analogue, if confirmed for other
      amyloidogenic peptides, may favor a new strategy for controlling fibril formation
      in a variety of human diseases.

PMID- 21078669
TI  - Engineered annexin A5 variants have impaired cell entry for molecular imaging of
      apoptosis using pretargeting strategies.
AB  - Phosphatidylserine (PS) on apoptotic cells is a target for diagnosis and therapy
      using annexin A5 (anxA5). Pretargeting is a strategy developed to improve signal
      to background ratio for molecular imaging and to minimize undesired side effects
      of pharmacological and radiotherapy. Pretargeting relies on accessibility of the
      target finder on the surface of the target cell. anxA5 binds PS and crystallizes
      in a two-dimensional network covering the PS-expressing cell surface. Two
      dimensional crystallization is the driving force for anxA5 internalization by PS
      expressing cells. Here, we report structure/function analysis of anxA5
      internalization. Guided by structural bioinformatics including protein-protein
      docking, we revealed that the amino acids Arg(63), Lys(70), Lys(101), Glu(138),
      Asp(139), and Asn(160) engage in intermolecular salt bridges within the anxA5
      trimer, which is the basic building block of the two-dimensional network.
      Disruption of the salt bridges by site-directed mutagenesis does not affect PS
      binding but inhibits trimer formation and cell entry of surface-bound anxA5. The
      anxA5 variants with impaired internalization are superior molecular imaging
      agents in pretargeting strategies as compared with wild-type anxA5.

PMID- 21078670
TI  - Engineered alterations in RNA editing modulate complex behavior in Drosophila:
      regulatory diversity of adenosine deaminase acting on RNA (ADAR) targets.
AB  - Select proteins involved in electrical and chemical neurotransmission are re
      coded at the RNA level via the deamination of particular adenosines to inosine by
      adenosine deaminases acting on RNA (ADARs). It has been hypothesized that this
      process, termed RNA editing, acts to "fine-tune" neurophysiological properties in
      animals and potentially downstream behavioral outputs. However, the extreme
      phenotypes resulting from deletions of adar loci have precluded investigations
      into the relationship between ADAR levels, target transcripts, and complex
      behaviors. Here, we engineer Drosophila hypomorphic for ADAR expression using
      homologous recombination. A substantial reduction in ADAR activity (>80%) leads
      to altered circadian motor patterns and abnormal male courtship, although
      surprisingly, general locomotor coordination is spared. The altered phenotypic
      landscape in our adar hypomorph is paralleled by an unexpected dichotomous
      response of ADAR target transcripts, i.e. certain adenosines are minimally
      affected by dramatic ADAR reduction, whereas editing of others is severely
      curtailed. Furthermore, we use a novel reporter to map RNA editing activity
      across the nervous system, and we demonstrate that knockdown of editing in
      fruitless-expressing neurons is sufficient to modify the male courtship song. Our
      data demonstrate that network-wide temporal and spatial regulation of ADAR
      activity can tune the complex system of RNA-editing sites and modulate multiple
      ethologically relevant behavioral modalities.

PMID- 21078671
TI  - MyoD directly up-regulates premyogenic mesoderm factors during induction of
      skeletal myogenesis in stem cells.
AB  - Gain- and loss-of-function experiments have illustrated that the family of
      myogenic regulatory factors is necessary and sufficient for the formation of
      skeletal muscle. Furthermore, MyoD required cellular aggregation to induce
      myogenesis in P19 embryonal carcinoma stem cells. To determine the mechanism by
      which stem cells can be directed into skeletal muscle, a time course of P19 cell
      differentiation was examined in the presence and absence of exogenous MyoD. By
      quantitative PCR, the first MyoD up-regulated transcripts were the premyogenic
      mesoderm factors Meox1, Pax7, Six1, and Eya2 on day 4 of differentiation.
      Subsequently, the myoblast markers myogenin, MEF2C, and Myf5 were up-regulated,
      leading to skeletal myogenesis. These results were corroborated by Western blot
      analysis, showing up-regulation of Pax3, Six1, and MEF2C proteins, prior to
      myogenin protein expression. To determine at what stage a dominant-negative
      MyoD/EnR mutant could inhibit myogenesis, stable cell lines were created and
      examined. Interestingly, the premyogenic mesoderm factors, Meox1, Pax3/7, Six1,
      Eya2, and Foxc1, were down-regulated, and as expected, skeletal myogenesis was
      abolished. Finally, to identify direct targets of MyoD in this system, chromatin
      immunoprecipitation experiments were performed. MyoD was observed associated with
      regulatory regions of Meox1, Pax3/7, Six1, Eya2, and myogenin genes. Taken
      together, MyoD directs stem cells into the skeletal muscle lineage by binding and
      activating the expression of premyogenic mesoderm genes, prior to activating
      myoblast genes.

PMID- 21078672
TI  - KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1
      function by impairing the recruitment of positive transcription elongation factor
      b to the hsp70 promoter.
AB  - Heat shock factor 1 (HSF1) is the master switch for heat shock protein (HSP)
      expression in eukaryotes. A synthetic chemical library was screened to identify
      inhibitors of HSF1 using a luciferase reporter under the control of a heat shock
      element. A compound named KRIBB11 (N(2)-(1H-indazole-5-yl)-N(6)-methyl-3
      nitropyridine-2,6-diamine) was identified for its activity in abolishing the heat
      shock-induced luciferase activity with an IC(50) of 1.2 MUmol/liter. When the
      cells were exposed to heat shock in the presence of KRIBB11, the induction of
      HSF1 downstream target proteins such as HSP27 and HSP70 was blocked. In addition,
      treatment of HCT-116 cells with KRIBB11 induced growth arrest and apoptosis.
      Markers of apoptosis, such as cleaved poly(ADP-ribose) polymerase, were detected
      after KRIBB11 treatment. Biotinyl-KRIBB11 was synthesized as an affinity probe
      for the identification of KRIBB11 target proteins. Using affinity chromatography
      and competition assays, KRIBB11 was shown to associate with HSF1 in vitro.
      Chromatin immunoprecipitation analysis showed that KRIBB11 inhibited HSF1
      dependent recruitment of p-TEFb (positive transcription elongation factor b) to
      the hsp70 promoter. Finally, intraperitoneal treatment of nude mice with KRIBB11
      at 50 mg/kg resulted in a 47.4% (p < 0.05) inhibition of tumor growth without
      body weight loss. Immunoblotting assays showed that the expression of HSP70 was
      lower in KRIBB11-treated tumor tissue than in control tissues. Because HSPs are
      expressed at high levels in a wide range of tumors, these results strengthen the
      rationale for targeting HSF1 in cancer therapy.

PMID- 21078673
TI  - Characterization of the elongation complex of dengue virus RNA polymerase:
      assembly, kinetics of nucleotide incorporation, and fidelity.
AB  - Dengue virus (DENV) infects 50-100 million people worldwide per year, causing
      severe public health problems. DENV RNA-dependent RNA polymerase, an attractive
      target for drug development, catalyzes de novo replication of the viral genome in
      three phases: initiation, transition, and elongation. The aim of this work was to
      characterize the mechanism of nucleotide addition catalyzed by the polymerase
      domain of DENV serotype 2 during elongation using transient kinetic methods. We
      measured the kinetics of formation of the elongation complex containing the
      polymerase and a double-stranded RNA by preincubation experiments. The elongation
      complex assembly is slow, following a one-step binding mechanism with an
      association rate of 0.0016 +/- 0.0001 MUM(-1) s(-1) and a dissociation rate of
      0.00020 +/- 0.00005 s(-1) at 37  degrees C. The elongation complex assembly is 6
      times slower at 30  degrees C and requires Mg(2+) during preincubation. The
      assembled elongation complex incorporates a correct nucleotide, GTP, to the
      primer with a K(d) of 275 +/- 52 MUM and k(pol) of 18 +/- 1 s(-1). The fidelity
      of the polymerase is 1/34,000, 1/59,000, 1/135,000 for misincorporation of UTP,
      ATP, and CTP opposite CMP in the template, respectively. The fidelity of DENV
      polymerase is comparable with HIV reverse transcriptase and the poliovirus
      polymerase. This work reports the first description of presteady-state kinetics
      and fidelity for an RNA-dependent RNA polymerase from the Flaviviridae family.

PMID- 21078674
TI  - Immunochemical analysis of the electronegative LDL subfraction shows that
      abnormal N-terminal apolipoprotein B conformation is involved in increased
      binding to proteoglycans.
AB  - Electronegative LDL (LDL(-)) is a minor subfraction of modified LDL present in
      plasma. Among its atherogenic characteristics, low affinity to the LDL receptor
      and high binding to arterial proteoglycans (PGs) could be related to
      abnormalities in the conformation of its main protein, apolipoprotein B-100 (apoB
      100). In the current study, we have performed an immunochemical analysis using
      monoclonal antibody (mAb) probes to analyze the conformation of apoB-100 in LDL(
      ). The study, performed with 28 anti-apoB-100 mAbs, showed that major differences
      of apoB-100 immunoreactivity between native LDL and LDL(-) concentrate in both
      terminal extremes. The mAbs Bsol 10, Bsol 14 (which recognize the amino-terminal
      region), Bsol 2, and Bsol 7 (carboxyl-terminal region) showed increased
      immunoreactivity in LDL(-), suggesting that both terminal extremes are more
      accessible in LDL(-) than in native LDL. The analysis of in vitro-modified LDLs,
      including LDL lipolyzed with sphingomyelinase (SMase-LDL) or phospholipase A(2)
      (PLA(2)-LDL) and oxidized LDL (oxLDL), suggested that increased amino-terminal
      immunoreactivity was related to altered conformation due to aggregation. This was
      confirmed when the aggregated subfractions of LDL(-) (agLDL(-)) and oxLDL (ag
      oxLDL) were isolated and analyzed. Thus, Bsol 10 and Bsol 14 immunoreactivity was
      high in SMase-LDL, ag-oxLDL, and agLDL(-). The altered amino-terminal apoB-100
      conformation was involved in the increased PG binding affinity of agLDL(-)
      because Bsol 10 and Bsol 14 blocked its high PG-binding. These observations
      suggest that an abnormal conformation of the amino-terminal region of apoB-100 is
      responsible for the increased PG binding affinity of agLDL(-).

PMID- 21078675
TI  - Thr-370 is responsible for CDK11(p58) autophosphorylation, dimerization, and
      kinase activity.
AB  - CDK11(p58), a member of the p34(cdc2)-related kinase family, is associated with
      cell cycle progression, tumorigenesis, and proapoptotic signaling. It is also
      required for the maintenance of chromosome cohesion, the maturation of
      centrosome, the formation of bipolar spindle, and the completion of mitosis. Here
      we identified that CDK11(p58) interacted with itself to form homodimers in cells,
      whereas D224N, the kinase-dead mutant, failed to form homodimers. CDK11(p58) was
      autophosphorylated, and the main functions of CDK11(p58), such as kinase
      activity, transactivation of nuclear receptors, and proapoptotic signal
      transduction, were dependent on its autophosphorylation. Furthermore, the in
      vitro kinase assay indicated that CDK11(p58) was autophosphorylated at Thr-370.
      By mutagenesis, we created CDK11(p58) T370A and CDK11(p58) T370D, which mimic the
      dephosphorylated and phosphorylated forms of CDK11(p58), respectively. The T370A
      mutant could not form dimers and be phosphorylated by the wild type CDK11(p58)
      and finally lost the kinase activity. Further functional research revealed that
      T370A failed to repress the transactivation of androgen receptor and enhance the
      cell apoptosis. Overall, our data indicated that Thr-370 is responsible for the
      autophosphorylation, dimerization, and kinase activity of CDK11(p58). Moreover,
      Thr-370 mutants might affect CDK11(p58)-mediated signaling pathways.

PMID- 21078676
TI  - p38 MAPK activation is downstream of the loss of intercellular adhesion in
      pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is a potentially fatal blistering disease characterized
      by autoantibodies against the desmosomal adhesion protein desmoglein (Dsg) 3.
      Whether autoantibody steric hindrance or signaling through pathways such as p38
      MAPK is primary in disease pathogenesis is controversial. PV mAbs that cause
      endocytosis of Dsg3 but do not dissociate keratinocytes because of compensatory
      adhesion by Dsg1 do not activate p38. The same mAbs plus exfoliative toxin to
      inactivate Dsg1 but not exfoliative toxin alone activate p38, suggesting that p38
      activation is secondary to loss of adhesion. Mice with epidermal p38alpha
      deficiency blister after passive transfer of PV mAbs; however, acantholytic cells
      retain cell surface Dsg3 compared with wild-type mice. In cultured keratinocytes,
      p38 knockdown prevents loss of desmosomal Dsg3 by PV mAbs, and exogenous p38
      activation causes internalization of Dsg3, desmocollin 3, and desmoplakin.
      p38alpha MAPK is therefore not required for the loss of intercellular adhesion in
      PV, but may function downstream to augment blistering via Dsg3 endocytosis.
      Treatments aimed at increasing keratinocyte adhesion could be used in conjunction
      with immunosuppressive agents, potentially leading to safer and more effective
      combination therapy regimens.

PMID- 21078677
TI  - PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its
      depolymerase activity.
AB  - During cell division, interaction between kinetochores and dynamic spindle
      microtubules governs chromosome movements. The microtubule depolymerase mitotic
      centromere-associated kinesin (MCAK) is a key regulator of mitotic spindle
      assembly and dynamics. However, the regulatory mechanisms underlying its
      depolymerase activity during the cell cycle remain elusive. Here, we showed that
      PLK1 is a novel regulator of MCAK in mammalian cells. MCAK interacts with PLK1 in
      vitro and in vivo. The neck and motor domain of MCAK associates with the kinase
      domain of PLK1. MCAK is a novel substrate of PLK1, and the phosphorylation
      stimulates its microtubule depolymerization activity of MCAK in vivo.
      Overexpression of a polo-like kinase 1 phosphomimetic mutant MCAK causes a
      dramatic increase in misaligned chromosomes and in multipolar spindles in mitotic
      cells, whereas overexpression of a nonphosphorylatable MCAK mutant results in
      aberrant anaphase with sister chromatid bridges, suggesting that precise
      regulation of the MCAK activity by PLK1 phosphorylation is critical for proper
      microtubule dynamics and essential for the faithful chromosome segregation. We
      reasoned that dynamic regulation of MCAK phosphorylation by PLK1 is required to
      orchestrate faithful cell division, whereas the high levels of PLK1 and MCAK
      activities seen in cancer cells may account for a mechanism underlying the
      pathogenesis of genomic instability.

PMID- 21078678
TI  - V3 versican isoform alters the behavior of human melanoma cells by interfering
      with CD44/ErbB-dependent signaling.
AB  - Versican is a hyaluronan-binding, extracellular chondroitin sulfate proteoglycan
      produced by several tumor types, including malignant melanoma, which exists as
      four different splice variants. The short V3 isoform contains the G1 and G3
      terminal domains of versican that may potentially interact directly or indirectly
      with the hyaluronan receptor CD44 and the EGFR, respectively. We have previously
      described that overexpression of V3 in MeWo human melanoma cells markedly reduces
      tumor cell growth in vitro and in vivo. In this study we have investigated the
      signaling mechanism of V3 by silencing the expression of CD44 in control and V3
      expressing melanoma cells. Suppression of CD44 had the same effects on cell
      proliferation and cell migration than those provoked by V3 expression, suggesting
      that V3 acts through a CD44-mediated mechanism. Furthermore, CD44-dependent
      hyaluronan internalization was blocked by V3 expression and CD44 silencing,
      leading to an accumulation of this glycosaminoglycan in the pericellular matrix
      and to changes in cell migration on hyaluronan. Furthermore, ERK1/2 and p38
      activation after EGF treatment were decreased in V3-expressing cells suggesting
      that V3 may also interact with the EGFR through its G3 domain. The existence of a
      EGFR/ErbB2 receptor complex able to interact with CD44 was identified in MeWo
      melanoma cells. V3 overexpression resulted in a reduced interaction between
      EGFR/ErbB2 and CD44 in response to EGF treatment. Our results indicate that the
      V3 isoform of versican interferes with CD44 and the CD44-EGFR/ErbB2 interaction,
      altering the signaling pathways, such as ERK1/2 and p38 MAPK, that regulate cell
      proliferation and migration.

PMID- 21078680
TI  - A telemedicine service for HIV/AIDS physicians working in developing countries.
AB  - In 2003, the Institute of Tropical Medicine (ITM) in Antwerp set up an Internet
      based decision support service to assist health-care workers in the management of
      difficult HIV/AIDS cases. This service is available to physicians working in
      resource-limited settings. Between April 2003 and December 2009, the telemedicine
      service received 1058 queries, from more than 40 countries, mostly resource
      constrained. In the first six years there were 952 queries, of which 459 (49%)
      were posted on the web-based telemedicine discussion forum and the rest sent by
      email. All queries were handled by a co-ordinator who forwarded them to a network
      of specialists, based at the ITM and at other institutions. The average time to
      provide a first reply was 24 hours. Almost half of the queries received in the
      first six years (n = 466) were related to the use of antiretroviral medications.
      The response rate to a user questionnaire was 19% (73 questionnaires returned out
      of 387 delivered): half of those (n = 37) came from active users and the
      remainder (n = 36) from clinicians who had never used the system. The user survey
      showed that telemedicine advice was valuable in the management of specific cases,
      and significantly influenced the way that clinicians managed other similar cases
      subsequently. Nonetheless, there was a declining trend in the rate of use of the
      service.

PMID- 21078681
TI  - Efficacy and tolerability of rizatriptan for the treatment of acute migraine in
      sumatriptan non-responders.
AB  - OBJECTIVE: The study was carried out to assess the efficacy and tolerability of
      rizatriptan orally disintegrating tablet (ODT) for treating acute migraine in
      patients who are non-responders to sumatriptan. BACKGROUND: Many migraineurs
      report dissatisfaction with sumatriptan efficacy. It is unclear whether
      sumatriptan 100 mg non-responders will respond to other triptans. METHODS: This
      was a randomized, placebo-controlled, double-blind study in adults with >1-year
      history of ICHD-II (International Classification of Headache Disorders, second
      edition) migraine who reported that they generally do not respond to sumatriptan
      (>=50% unsatisfactory response). In the baseline phase, participants treated a
      single moderate/severe migraine attack with open-label generic sumatriptan 100
      mg. Those who continued to experience moderate/severe pain at two hours post-dose
      were eligible to enter the double-blind treatment phase, during which
      participants treated three migraine attacks in crossover fashion (two with
      rizatriptan 10-mg ODT, one with placebo) after being randomly assigned to one of
      three treatment sequences (1 : 1 : 1 ratio). The primary endpoint was two-hour
      pain relief. RESULTS: A total of 102 (94%) participants treated at least one
      study migraine. Pain relief at two hours was significantly greater with
      rizatriptan compared with placebo (51% vs. 20%, p < .001). Response rates also
      favored rizatriptan on two-hour pain freedom (22% vs. 12%, p = .013) as well as
      24-hour sustained pain relief (38% vs. 14%, p < .001) and sustained pain freedom
      (20% vs. 11%, p = .036). Treatment was generally well tolerated. CONCLUSION:
      Rizatriptan 10-mg ODT was superior to placebo at providing two-hour pain relief
      and two-hour pain freedom in the treatment of acute migraine in those who do not
      respond to sumatriptan 100 mg. Rizatriptan was generally well tolerated in this
      population.

PMID- 21078679
TI  - Probing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a
      nanometric scale.
AB  - Cationic lipids are used for delivering nucleic acids (lipoplexes) into cells for
      both therapeutic and biological applications. A better understanding of the
      identified key-steps, including endocytosis, endosomal escape and nuclear
      delivery is required for further developments to improve their efficacy. Here, we
      developed a labelling protocol using aminated nanoparticles as markers for
      plasmid DNA to examine the intracellular route of lipoplexes in cell lines using
      transmission electron microscopy. Morphological changes of lipoplexes, membrane
      reorganizations and endosomal membrane ruptures were observed allowing the
      understanding of the lipoplex mechanism until the endosomal escape mediated by
      cationic lipids. The study carried out on two cationic lipids, bis(guanidinium)
      tris(2-aminoethyl)amine-cholesterol (BGTC) and dioleyl succinyl paramomycin
      (DOSP), showed two pathways of endosomal escape that could explain their
      different transfection efficiencies. For BGTC, a partial or complete dissociation
      of DNA from cationic lipids occurred before endosomal escape while for DOSP,
      lipoplexes remained visible within ruptured vesicles suggesting a more direct
      pathway for DNA release and endosome escape. In addition, the formation of new
      multilamellar lipid assemblies was noted, which could result from the interaction
      between cationic lipids and cellular compounds. These results provide new
      insights into DNA transfer pathways and possible implications of cationic lipids
      in lipid metabolism.

PMID- 21078682
TI  - Causal attributions, pathway to care and clinical features of first-episode
      psychosis: a South African perspective.
AB  - BACKGROUND: Causal belief systems and help-seeking practices may impact on
      pathway to care and features of first-episode psychosis (FEP) that have
      prognostic value. This is particularly relevant in South Africa where many people
      subscribe to traditional belief systems and consult traditional healers. AIM: To
      evaluate the relationship between causal attributions and pathway to care and
      features of FEP that have prognostic value. METHOD: We tested associations
      between causal attributions and pathway to care and duration of untreated
      psychosis (DUP), age of onset, PANSS-rated positive, negative and general
      symptoms and depressive symptoms (Calgary Depression Scale) in a sample of 54 FEP
      patients. RESULTS: Spiritual attribution of cause (49% of patients) was
      associated with long DUP, while consultation with a traditional healer (39% of
      patients) was associated with long DUP and high negative symptoms. Only 19% had
      consulted a psychiatrist. Seventy nine per cent (79%) were referred to hospital
      by family, police were involved in 44% of admissions, and 81% were admitted
      involuntarily. CONCLUSIONS: Spiritual attributions of cause and previous
      consultation with traditional healers may delay entry to psychiatric care and
      thereby negatively impact on prognosis of FEP. This highlights the importance of
      mental health education and developing a positive collaborative relationship with
      traditional healers, especially in low- and middle-income countries.

PMID- 21078683
TI  - Effective communication is crucial to self-management: the experiences of
      immigrants to Australia living with diabetes.
AB  - OBJECTIVES: Ageing immigrant populations now pose problems for the management of
      chronic illness in Australia. This article asks questions about the experiences
      of immigrants in Australia with type II diabetes mellitus (DM). What impact, if
      any, have health policies had on the lives of immigrants? How do their
      experiences of living with DM compare with those of people with DM who were born
      in Australia? METHODS: Semi-structured interviews were conducted with 32
      participants who had DM (n = 25) or cared for someone with DM (n = 7). Fifteen
      participants had migrated to Australia and English was not their first language.
      Participants were asked to describe their experience of managing diabetes.
      RESULTS: Immigrants to Australia confront linguistic and cultural barriers that
      create an extra layer of problems not experienced by Australian-born people.
      Older people who were born overseas face obstacles to effective engagement with
      the health system that weaken their ability to take an active part in the
      management of their conditions. CONCLUSIONS: Chronic disease policy is failing
      immigrants to Australia. Health professionals and services must recognize the
      central role that cultural diversity plays in self-management and the impact that
      this can have on health outcomes for immigrants with chronic illness.

PMID- 21078685
TI  - Q192R polymorphism of the paraoxonase-1 gene as a risk factor for obesity in
      Portuguese women.
AB  - INTRODUCTION: Obesity became a major public health problem as a result of its
      increasing prevalence worldwide. Paraoxonase-1 (PON1) is an esterase able to
      protect membranes and lipoproteins from oxidative modifications. At the PON1
      gene, several polymorphisms in the promoter and coding regions have been
      identified. The aims of this study were i) to assess PON1 L55M and Q192R
      polymorphisms as a risk factor for obesity in women; ii) to compare PON1 activity
      according to the expression of each allele in L55M and Q192R polymorphisms; iii)
      to compare PON1 activity between obese and normal-weight women. MATERIALS AND
      METHODS: We studied 75 healthy (35.9 +/- 8.2 years) and 81 obese women (34.3 +/-
      8.2 years). Inclusion criteria for obese subjects were body mass index >= 30 
      kg/m2 and absence of inflammatory/neoplasic conditions or kidney/hepatic
      dysfunction. The two PON1 polymorphisms were assessed by real-time PCR with
      TaqMan probes. PON1 enzymatic activity was assessed by spectrophotometric
      methods, using paraoxon as a substrate. RESULTS: No significant differences were
      found for PON1 activity between normal and obese women. Nevertheless, PON1
      activity was greater (P < 0.01) for the RR genotype (in Q192R polymorphism) and
      for the LL genotype (in L55M polymorphism). The frequency of allele R of Q192R
      polymorphism was significantly higher in obese women (P < 0.05) and was
      associated with an increased risk of obesity (odds ratio = 2.0 - 95% confidence
      interval (1.04; 3.87)). CONCLUSION: L55M and Q192R polymorphisms influence PON1
      activity. The allele R of the Q192R polymorphism is associated with an increased
      risk for development of obesity among Portuguese Caucasian premenopausal women.

PMID- 21078686
TI  - Association between thyroid function tests at baseline and the outcome of
      patients with sepsis or septic shock: a systematic review.
AB  - INTRODUCTION: The severity of critical illness is associated with various
      patterns of thyroid hormone abnormalities. We sought to evaluate whether the
      outcome of patients with, specifically, sepsis or septic shock is associated with
      the thyroid function tests evaluated at diagnosis or admission in the intensive
      care unit (ICU). METHODS: We performed a systematic review of relevant studies by
      searching PubMed. RESULTS: We included nine studies that all had a prospective
      cohort design. Seven involved children or neonates, and two involved adults.
      Mortality was the outcome evaluated in eight studies, while the length of ICU
      stay was evaluated in the remaining study. In univariate analysis, six of the
      nine included studies showed that either, free or total, triiodothyronine or
      thyroxine was lower in the group of patients with sepsis or septic shock who had
      unfavorable outcome than in those who had favorable outcome. Two other studies
      showed higher TSH values in the group of patients with unfavorable outcome. No
      significant relevant findings were observed in the remaining study. Regarding the
      correlation of sepsis prognostic scoring systems with thyroid function tests, the
      three studies that provided specific relevant data showed variable findings.
      DISCUSSION: Most of the relevant studies identified favor the concept that
      decreased thyroid function at baseline might be associated with a worse outcome
      of patients with sepsis or septic shock. Although these findings are not
      consistent, the role of thyroid function in affecting or merely predicting the
      outcome of sepsis or septic shock merits further investigation.

PMID- 21078684
TI  - Beta cell function after weight loss: a clinical trial comparing gastric bypass
      surgery and intensive lifestyle intervention.
AB  - OBJECTIVE: The effects of various weight loss strategies on pancreatic beta cell
      function remain unclear. We aimed to compare the effect of intensive lifestyle
      intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell
      function. DESIGN: One year controlled clinical trial (ClinicalTrials.gov
      identifier NCT00273104). METHODS: One hundred and nineteen morbidly obese
      participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6
      (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m2, 84 women) were allocated to
      RYGB (n = 64) or ILI (n = 55). The patients underwent repeated oral glucose
      tolerance tests (OGTTs) and were categorised as having either normal (NGT) or
      abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT
      (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m2, 19 women) served as controls. OGTT
      based indices of beta cell function were calculated. RESULTS: One year weight
      reduction was 30% (8) after RYGB and 9% (10) after ILI (P < 0.001). Disposition
      index (DI) increased in all treatment groups (all P<0.05), although more in the
      surgery groups (both P < 0.001). Stimulated proinsulin-to-insulin (PI/I) ratio
      decreased in both surgery groups (both P < 0.001), but to a greater extent in the
      surgery group with AGT at baseline (P < 0.001). Post surgery, patients with NGT
      at baseline had higher DI and lower stimulated PI/I ratio than controls (both P <
      0.027). CONCLUSIONS: Gastric bypass surgery improved beta cell function to a
      significantly greater extent than ILI. Supra-physiological insulin secretion and
      proinsulin processing may indicate excessive beta cell function after gastric
      bypass surgery.

PMID- 21078687
TI  - Semele: a killer-male, rescue-female system for suppression and replacement of
      insect disease vector populations.
AB  - Two strategies to control mosquito-borne diseases, such as malaria and dengue
      fever, are reducing mosquito population sizes or replacing populations with
      disease-refractory varieties. We propose a genetic system, Semele, which may be
      used for both. Semele consists of two components: a toxin expressed in transgenic
      males that either kills or renders infertile wild-type female recipients and an
      antidote expressed in females that protects them from the effects of the toxin.
      An all-male release results in population suppression because wild-type females
      that mate with transgenic males produce no offspring. A release that includes
      transgenic females results in gene drive since females carrying the allele are
      favored at high population frequencies. We use simple population genetic models
      to explore the utility of the Semele system. We find that Semele can spread under
      a wide range of conditions, all of which require a high introduction frequency.
      This feature is desirable since transgenic insects released accidentally are
      unlikely to persist, transgenic insects released intentionally can be spatially
      confined, and the element can be removed from a population through sustained
      release of wild-type insects. We examine potential barriers to Semele gene drive
      and suggest molecular tools that could be used to build the Semele system.

PMID- 21078688
TI  - Transgene expression and transgene-induced silencing in diploid and
      autotetraploid Arabidopsis.
AB  - Previous studies have suggested that transgene expression in plants can be
      affected by ploidy. Here we show that three different transgenes, a reporter
      transgene, an antisense transgene, and a hairpin RNA (hpRNA) transgene, are all
      expressed at a lower level in autotetraploid (4n) than in diploid (2n)
      Arabidopsis. RNA silencing of two endogenous genes was induced by the antisense
      and hpRNA transgenes and this silencing is significantly less effective in 4n
      than in 2n Arabidopsis; furthermore, the reduced silencing in 4n Arabidopsis
      correlated with reduced accumulation of silencing-inducer RNAs. Methylation
      analysis both of independent 2n and 4n transgenic lines and of 2n and 4n progeny
      derived from the same 3n transgenic parent, indicated that transgenes are more
      methylated in 4n than 2n Arabidopsis. These results suggest that transgenes are
      transcriptionally repressed in the 4n background, resulting in expression levels
      lower than in the 2n background. Transgenes designed to silence endogenous genes
      express lower concentrations of silencing-inducer RNAs in 4n Arabidopsis plants,
      resulting in less effective silencing of target genes than in 2n Arabidopsis
      plants.

PMID- 21078690
TI  - Protective effects of pentoxifylline on cigarette smoking-induced renal tissue
      damage in rats.
AB  - In this study, we investigated the protective effect of pentoxifilline (PTX) on
      smoking-induced damage in rat kidney tissues. Twenty-seven male Wistar rats were
      used in the study. Animals were divided into three equal groups as follows: Group
      1: control group with only normal saline (NS; 0.9% NaCl) injection for 8 weeks;
      Group 2: cigarette smoking and NS injection for 8 weeks; and Group 3: cigarette
      smoking and PTX injection for 8 weeks. The rats were sacrificed after 8 weeks and
      their kidneys were excised for histopathological analysis. Serial paraffin
      sections (5 um) of the kidneys were cut and stained with hematoxylin and eosin
      (H&E) and periodic acid-Schiff (PAS). The terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method was
      used to assess apoptosis. Glomerular diameters, glomerular cell number and
      proximal tubule cell numbers were compared between the groups. Our results showed
      that PTX treatment prevented negative effects of smoking in rat kidneys. There
      was a statistically significant difference in all assessed parameters between
      Group 2 and other groups (p < 0.05). In conclusion, our study shows that PTX
      treatment is effective in preventing the negative effects of cigarette smoking on
      kidneys by inhibiting cell damage with its antioxidant properties.

PMID- 21078689
TI  - Antagonistic interactions between the cAMP-dependent protein kinase and Tor
      signaling pathways modulate cell growth in Saccharomyces cerevisiae.
AB  - Eukaryotic cells integrate information from multiple sources to respond
      appropriately to changes in the environment. Here, we examined the relationship
      between two signaling pathways in Saccharomyces cerevisiae that are essential for
      the coordination of cell growth with nutrient availability. These pathways
      involve the cAMP-dependent protein kinase (PKA) and Tor proteins, respectively.
      Although these pathways control a similar set of processes important for growth,
      it was not clear how their activities were integrated in vivo. The experiments
      here examined this coordination and, in particular, tested whether the PKA
      pathway was primarily a downstream effector of the TORC1 signaling complex. Using
      a number of reporters for the PKA pathway, we found that the inhibition of TORC1
      did not result in diminished PKA signaling activity. To the contrary, decreased
      TORC1 signaling was generally associated with elevated levels of PKA activity.
      Similarly, TORC1 activity appeared to increase in response to lower levels of PKA
      signaling. Consistent with these observations, we found that diminished PKA
      signaling partially suppressed the growth defects associated with decreased TORC1
      activity. In all, these data suggested that the PKA and TORC1 pathways were
      functioning in parallel to promote cell growth and that each pathway might
      restrain, either directly or indirectly, the activity of the other. The potential
      significance of this antagonism for the regulation of cell growth and overall
      fitness is discussed.

PMID- 21078691
TI  - Vitamin C protective role for alcoholic liver disease in mice through regulating
      iron metabolism.
AB  - Alcoholic liver disease (ALD) is a major medical complication of drinking
      alcohol, and commonly accompanied with hepatic iron overload and liver injuries.
      Oxidative stress plays an important role in pathogenesis of ALD and also leads to
      iron-metabolic disorders. In this study, the effects of vitamin C (Vc) on iron
      metabolism-related genes expression and liver protection from drinking in mice
      were investigated. Twenty-four male kunming mice were divided into four groups
      (six mice per group): control (water drinking); alcohol group (20% alcohol
      drinking), alcohol + low Vc group (adding 50 mg/kg Vc daily) and alcohol + high
      Vc group (adding 100 mg/kg Vc daily). All these mice were sacrificed after 7
      days. Vc can ameliorate the increase of sera alanine aminotransferase (ALT)
      activity and hepatic iron overload of drinking alcohol in mice. Vc increases the
      expression of the iron-regulated hormone hepcidin and decreases transferrin
      receptor 1 (TfR1) expression in liver. Vc also down-regulates the expression of
      ferroportin 1 (Fpn1) in the intestine and decreases the iron release to blood. In
      conclusion, Vc ameliorated the alcoholic liver injuries through regulating the
      iron metabolism-related genes expression.

PMID- 21078692
TI  - Changing epidemiology and clinical issues arising in an ageing cystic fibrosis
      population.
AB  - Improvements in the quality and implementation of medical care for individuals
      with cystic fibrosis (CF) have resulted in a dramatic improvement in survival.
      Many of these strategies have focused on the effective management of pulmonary
      disease which has delayed its manifestations into later years. With an increasing
      number of patients surviving to later years the impact of chronic inflammation
      and nutritional compromise on other organ systems over a lifetime are
      increasingly manifest. This review highlights the changing epidemiology of the
      ageing CF population and the complications that may ensue.

PMID- 21078693
TI  - Investigations of natural attenuation in groundwater near a landfill and
      implications for landfill post-closure.
AB  - The controlled landfill technology is now adopting passive attenuation techniques
      as an increasing number of landfill sites reach the post-closure phase. During
      the post-closure phase, landfill operators need to convince environmental
      authorities that landfills no longer pose a threat to health or the environment.
      The demonstration of acceptable risk should rely in particular on data collected
      during environmental monitoring in addition to modelling of possible future
      evolutions of environmental concentrations. One difficulty that is typically
      encountered in France is related to the fact that groundwater monitoring systems
      around landfills are often insufficiently detailed to provide conclusive evidence
      of natural attenuation mechanisms. This paper presents data on groundwater
      quality in the vicinity of an old landfill located in a complex aquifer system.
      While isotopic data show a signature of the landfill leachate in the groundwater
      in the vicinity of the landfill, chemical analyses do not suggest a strong
      influence, which could be indicative of natural attenuation mechanisms in the
      groundwater. However, the complexity of the groundwater system in this area is
      such that it cannot be excluded that a pollutant flux is being overlooked.
      Implications of demonstrating natural attenuation during the landfill post
      closure phase, with respect to groundwater monitoring, are discussed.

PMID- 21078694
TI  - Primary progressive versus relapsing-onset multiple sclerosis: presence and
      prognostic value of cerebrospinal fluid oligoclonal IgM.
AB  - BACKGROUND: There is increasing evidence on cerebrospinal fluid (CSF) oligoclonal
      IgM (OCIgM) predicting a more aggressive disease course in relapsing-remitting
      Multiple Sclerosis (MS), while there is a scarcity of data for primary
      progressive MS (PPMS). OBJECTIVE: Our aim was to investigate the presence and
      possible prognostic value of CSF OCIgM in a group of PPMS and in a group of
      relapsing-onset MS patients. The possible prognostic role of other clinical and
      biological factors was also evaluated. METHODS: We calculated the impact of
      single clinical and biological factors, including CSF OCIgM at onset, on the
      probability of reaching an Expanded Disability Status Scale of 3 and 4 in 45 PPMS
      and 104 relapsing-onset MS patients. RESULTS: CSF OCIgM were found in only 13% of
      PPMS patients and did not influence the time taken to reach an Expanded
      Disability Status Scale of 3 and 4. Conversely, they were present in 46% of
      relapsing-onset MS patients and increased the risk of reaching an Expanded
      Disability Status Scale of 4. Clinical factors with a negative prognostic value
      in PPMS were age at onset <30 years and onset with pyramidal symptoms, while
      onset with sensory symptoms in relapsing-onset MS predicted a more favourable
      course. CONCLUSION: This study confirms that, in relapsing-onset MS patients, the
      presence of CSF OCIgM at onset predicts a worse disease course. In the cohort of
      PPMS patients, however, CSF OCIgM were rare, suggesting that heterogeneous
      pathogenetic mechanisms may be involved in the different MS forms.

PMID- 21078695
TI  - CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for
      JC virus.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is associated with
      natalizumab treatment in patients with multiple sclerosis (MS). It has been
      hypothesized that natalizumab mobilizes JC virus (JCV)-infected haematopoietic
      progenitor cells mediating viraemia and subsequently this disease. OBJECTIVE: The
      objective of this study was to investigate peripheral haematopoietic progenitor
      cells for evidence of JCV DNA in MS patients treated with natalizumab. METHODS:
      We assessed JCV and cytomegalovirus (CMV) DNA in magnetically separated CD34+
      haematopoietic progenitor cells, peripheral blood mononuclear cells and plasma of
      67 natalizumab-treated patients with MS and six PML patients. RESULTS: Viral DNA
      was not detectable in CD34+ haematopoietic progenitor or peripheral blood
      mononuclear cells from any sample. Two plasma samples from patients with MS while
      undergoing natalizumab treatment were JCV-positive. In one case clinically
      manifest PML developed 8 months thereafter. CONCLUSIONS: Our findings do not
      support the hypothesis that natalizumab mobilizes JC virus-infected CD34+ cells
      from the bone marrow mediating JC viraemia. Notably, JC viraemia was detected in
      one patient with MS prior to developing clinical PML. This warrants further
      study.

PMID- 21078696
TI  - Children and young people's views of health professionals in England.
AB  - In recent years increased attention has been focused on listening to the views of
      children and young people. This study analysed 31 research studies, which were
      published between 2000 and early 2009, into children and young people's views of
      health professionals in England. The findings from the studies were inductively
      analysed and grouped into seven themes. Children and young people want health
      professionals to be familiar, accessible and available; to be informed and
      competent; to provide accessible information; to be a good communicator; to
      participate in care; to ensure privacy and confidentiality, and to demonstrate
      acceptance and empathy. It is noteworthy that over the nine years many studies
      repeated the same broad messages to health professionals. The findings suggest
      that although there are examples of good practice, health professionals are
      sometimes falling short of the standards set by UK health professional bodies.

PMID- 21078697
TI  - Dietary habits, economic status, academic performance and body mass index in
      school children: a comparative study.
AB  - The changes in dietary habits and way of life of adolescents can lead to some
      nutrition problems. The purpose of this study was to compare dietary habits of
      children living in metropolitan and non-metropolitan areas regarding their
      physical characteristics, socio-economic milieu and educational level. A total of
      737 students studying in the 6th, 7th and 8th grades of two different primary
      schools took part in the study. Data were collected by a questionnaire including
      dietary habits of participants. Furthermore, the weight and height of students
      were measured and their body mass index was calculated. During the study, while
      4.3 percent of students living in the non-metropolitan area were found obese,
      this figure was 8.4 percent in the metropolitan area. A big majority of non
      metropolitan students have breakfast and lunch at home. Metropolitan students not
      having lunch at home have their lunch at restaurants or school canteens and
      generally consume more snacks. The obesity risk of students participating in the
      study was found to be high. Intervention programs should be organized in order to
      inform the students about the importance of healthy nutrition and lead them to
      change their current consumption behavior.

PMID- 21078698
TI  - Parents' attitudes to smoking and passive smoking and their experience of the
      tobacco preventive work in child health care.
AB  - The purpose of this study was to describe parents' attitudes to smoking and their
      experience of the tobacco preventive work in antenatal care and in Child Health
      Care (CHC) in Sweden. A population based survey in which 62 percent of 3000
      randomly selected parents with 1- and 3-year-old children answered a
      questionnaire. Fifty-six percent stated that smoking was registered in the health
      record of the child yet no further discussion regarding passive smoking took
      place. The parents' educational level and smoking status was related to the
      attitudes and experiences of the tobacco preventive work. The results indicated
      that the dialogue with parents regarding children and environmental tobacco smoke
      (ETS) exposure has to be redesigned and intensified in order to meet the needs of
      parents with different backgrounds.

PMID- 21078699
TI  - Habitual physical activity can be increased in people with cerebral palsy: a
      systematic review.
AB  - OBJECTIVE: To determine if habitual physical activity could be increased in
      people with cerebral palsy. DATA SOURCES: We searched electronic databases until
      February 2010 using key words related to concepts of cerebral palsy and physical
      activity. This search was supplemented with citation tracking. METHODS: Studies
      had to include participants with cerebral palsy who have habitual physical
      activity measured over at least one day after a therapy intervention. Two
      reviewers independently assessed study quality with the PEDro scale (quantitative
      studies) and Critical Appraisal Checklist for Qualitative Research (qualitative
      studies). For quantitative studies standardized mean differences were calculated
      and meta-analysis conducted. Qualitative data were synthesized thematically.
      RESULTS: Three randomized controlled trials (96 participants) and two qualitative
      studies (21 participants) were reviewed. Four studies evaluated exercise
      programmes, and one study an online educational and support programme. Meta
      analysis showed that exercise programmes could increase habitual physical
      activity (delta = 1.0; 95% confidence interval (CI) 0.28 to 1.72). This result
      was reinforced by reports of increased daily activity in two qualitative studies.
      The online programme increased weekly minutes of moderate to vigorous physical
      activity (d = 0.81; 95% CI 0.17 to 1.45), and weekly step counts (d = 0.62; 95%
      CI 0.0 to 1.25). Positive effects were not maintained after programmes stopped.
      There was insufficient evidence to determine if demographic factors or programme
      characteristics, such as intensity and setting, were associated with outcomes.
      CONCLUSION: Preliminary evidence suggests that exercise programmes and online
      support programmes can increase habitual physical activity in people with
      cerebral palsy, but effects are not maintained when programmes stop.

PMID- 21078701
TI  - The effects of verbal instructions on gait in people with Parkinson's disease: a
      systematic review of randomized and non-randomized trials.
AB  - OBJECTIVE: To collate and appraise empirical evidence relating to the effects of
      verbal instructions (verbal commands given by another person) on stride length,
      gait velocity and stride variability in people with Parkinson's disease. DATA
      SOURCES: Cinahl, Cochrane, Embase, Medline, PEDro, PsycINFO and Web of Science.
      REVIEW METHODS: Independent reviewers extracted data from eligible studies and
      assessed methodological quality. The level of evidence was determined by best
      evidence synthesis based upon the experimental design, methodological quality and
      statistical findings of individual studies. RESULTS: One randomized controlled
      study and 12 non-controlled studies fulfilled the selection criteria and involved
      149 participants. Five types of verbal instructions were examined which included
      'take big steps', 'walk fast', 'swing arms when walking', 'count rhythm when
      walking' and 'walk fast with big steps'. Best evidence synthesis found indicative
      evidence in support of the use of the instruction to take big steps in walking
      training for stride length improvement in people with mild to moderate
      Parkinson's disease who are without cognitive impairment. There was insufficient
      evidence in support of effects on gait velocity and stride variability. There was
      also insufficient evidence in support of effects of other instructions on any of
      the gait variables. CONCLUSION: The empirical evidence in support of the benefits
      from verbal instructions is weak. The evidence is limited to short-term stride
      length improvement from the use of the instruction to take big steps in walking
      training.

PMID- 21078700
TI  - The immediate effects of diacutaneous fibrolysis on pain and mobility in patients
      suffering from painful shoulder: a randomized placebo-controlled pilot study.
AB  - OBJECTIVES: To describe the immediate effects of diacutaneous fibrolysis on pain
      and mobility in patients suffering from painful shoulder, and to assess the
      ability of the placebo technique to blind participants to group allocation.
      DESIGN: A double-blind before-after randomized placebo-controlled pilot study.
      SETTING: Two public centres of Primary Health Care of the Spanish National Health
      System. PARTICIPANTS: Fifty patients (29 women, 21 men) with a diagnosis of
      painful shoulder of subacromial origin were included. INTERVENTION: Participants
      were randomly allocated to one of two groups. The intervention group (N = 25) was
      actually treated with diacutaneous fibrolysis, while the placebo group (N = 25)
      was treated with placebo diacutaneous fibrolysis. MEASUREMENTS: Active range of
      motion (flexion, abduction, extension, external and internal rotation) and pain
      intensity in the hand-behind-back position were measured. Participants were also
      asked about their perception in terms of comfort of the technique and results
      obtained. RESULTS: Between-groups differences were significant in flexion (mean
      11.4 degrees; 95% confidence interval (CI) 5.7-17.1), abduction (mean 7.2
      degrees; 95% CI 2.0-12.5) and internal rotation movements (mean 3.1 cm; 95% CI
      0.1-6.1). There were no significant differences between groups in pain intensity,
      extension or external rotation movements. The placebo technique showed its
      ability to blind participants to group allocation. None of the participants
      suffered any adverse effects from diacutaneous fibrolysis. CONCLUSION:
      Diacutaneous fibrolysis may be an effective and safe therapeutic option to
      improve active range of motion in patients suffering from painful shoulder.

PMID- 21078702
TI  - A pragmatic randomized controlled study of the effectiveness and cost
      consequences of exercise therapy in hip osteoarthritis.
AB  - OBJECTIVE: To evaluate the short- and long-term effectiveness of exercise
      training in relation to pain, function and direct costs to health care systems
      attributable to hip osteoarthritis. DESIGN: Prospective, two-year randomized
      controlled trial. SETTING: An outpatient primary health care setting. SUBJECTS:
      One hundred and twenty men and women aged from 55 to 80, with radiologically
      diagnosed hip osteoarthritis with associated clinical symptoms. INTERVENTIONS:
      The combined exercise and general practitioner (GP) care group received 12
      supervised (once per week) exercise sessions at the baseline and four additional
      booster sessions one year later. Both groups received standard GP care. MAIN
      MEASURES: The WOMAC Osteoarthritis Index, physical functioning score of RAND-36
      (SF-36), the use and health care system costs of doctor visits and physiotherapy
      associated with hip osteoarthritis, number of total hip replacements, the use of
      analgesic and non-steroidal anti-inflammatory drugs (NSAIDs), performance-based
      outcome scores and body mass index (BMI). RESULTS: There were no differences
      between the groups with respect to WOMAC hip pain, physical functioning score of
      RAND-36, performance-based outcome scores or BMI. The effect of the exercise
      intervention on WOMAC function was statistically significant at 6 months (mean = 
      7.5; 95% confidence interval (CI) -13.9 to -1.0; P = 0.02) and 18 months (mean = 
      7.9; 95% CI -15.3 to -0.4; P = 0.04). There were no statistically significant
      differences in the total health care system costs between the groups. CONCLUSION:
      The mostly home-based exercise training programme provided in this study did not
      result in reduced hip pain over the two-year follow-up period.

PMID- 21078703
TI  - Using systemic approaches, methods and techniques in rehabilitation medicine.
AB  - This series of articles for rehabilitation in practice aims to cover a knowledge
      element of the rehabilitation medicine curriculum. Nevertheless they are intended
      to be of interest to a multidisciplinary audience. The competency addressed in
      this article is 'The trainee demonstrates a knowledge of benefits and limitations
      of counselling approaches, specifically in this article systemic family therapy.'

PMID- 21078704
TI  - Association of frontal and posterior cortical gray matter volume with time to
      alcohol relapse: a prospective study.
AB  - OBJECTIVE: Alcoholism is associated with gray matter volume deficits in frontal
      and other brain regions. Whether persistent brain volume deficits in abstinence
      are predictive of subsequent time to alcohol relapse has not been established.
      The authors measured gray matter volumes in healthy volunteers and in a sample of
      treatment-engaged, alcohol-dependent patients after 1 month of abstinence and
      assessed whether smaller frontal gray matter volume was predictive of subsequent
      alcohol relapse outcomes. METHOD: Forty-five abstinent alcohol-dependent patients
      in treatment and 50 healthy comparison subjects were scanned once using high
      resolution (T(1)-weighted) structural MRI, and voxel-based morphometry was used
      to assess regional brain volume differences between the groups. A prospective
      study design was used to assess alcohol relapse in the alcohol-dependent group
      for 90 days after discharge from 6 weeks of inpatient treatment. RESULTS:
      Significantly smaller gray matter volume in alcohol-dependent patients relative
      to comparison subjects was seen in three regions: the medial frontal cortex, the
      right lateral prefrontal cortex, and a posterior region surrounding the parietal
      occipital sulcus. Smaller medial frontal and parietal-occipital gray matter
      volumes were each predictive of shorter time to any alcohol use and to heavy
      drinking relapse. CONCLUSIONS: These findings are the first to demonstrate that
      gray matter volume deficits in specific medial frontal and posterior parietal
      occipital brain regions are predictive of an earlier return to alcohol use and
      relapse risk, suggesting a significant role for gray matter atrophy in poor
      clinical outcomes in alcoholism. Extent of gray matter volume deficits in these
      regions could serve as useful neural markers of relapse risk and alcoholism
      treatment outcome.

PMID- 21078705
TI  - Real-time electronic ambulatory monitoring of substance use and symptom
      expression in schizophrenia.
AB  - OBJECTIVE: Despite evidence demonstrating elevated comorbidity between
      schizophrenia and substance use disorders, the underlying mechanisms of
      association remain poorly understood. The brief time intervals that characterize
      interactions between substance use and psychotic symptoms in daily life are
      inaccessible to standard research protocols. The authors used electronic personal
      digital assistants (PDAs) to examine the temporal association of diverse forms of
      substance use with psychotic symptoms and psychological states in natural
      contexts. METHOD: Of 199 community-dwelling individuals with schizophrenia or
      schizoaffective disorder who were contacted to participate in the study, 92%
      accepted and 73% completed the study. The 145 participants who completed the
      study provided reports of substance use, psychotic symptoms, mood, and event
      negativity multiple times per day over 7 consecutive days through PDAs. RESULTS:
      Participants responded to 72% of the electronic interviews (N=2,737) across daily
      life contexts. Strong within-day prospective associations were observed in both
      directions between substance use and negative psychological states or psychotic
      symptoms, but considerable variation was observed by substance type. Consistent
      with the notion of self-medication, alcohol use was most likely to follow
      increases in anxious mood or psychotic symptoms. Cannabis and other illicit
      substances, demonstrating more complex patterns, were more likely to follow
      certain psychological states but were also associated with the later onset of
      psychotic symptoms. CONCLUSIONS: The dynamic interplay of substance use and
      psychotic symptoms is in many cases consistent with both causal and self
      medication mechanisms, and these patterns of association should be considered in
      the design of treatment and prevention strategies.

PMID- 21078706
TI  - Pre-existing high glucocorticoid receptor number predicting development of
      posttraumatic stress symptoms after military deployment.
AB  - OBJECTIVE: The development of posttraumatic stress disorder (PTSD) is influenced
      by preexisting vulnerability factors. The authors aimed at identifying a
      preexisting biomarker representing a vulnerability factor for the development of
      PTSD. To that end, they determined whether the dexamethasone binding capacity of
      leukocytes, as a measure of glucocorticoid receptor (GR) number, before exposure
      to trauma was a predictor of development of PTSD symptoms. In addition, the
      authors analyzed mRNA expression for GR subtypes and GR target genes. METHOD:
      Participants were selected from a large prospective study on deployment-related
      disorders, in which peripheral blood mononuclear cells (PBMCs) were obtained
      prior to and 1 and 6 months after military deployment. Participants included
      armed forces personnel with high levels of PTSD symptoms 6 months after
      deployment (N=34) and comparison subjects without high levels of PTSD or
      depressive symptoms (N=34) matched for age, rank, previous deployments,
      educational level, and function during deployment. RESULTS: Before military
      deployment, the GR number in PBMCs was significantly higher in participants who
      developed high levels of PTSD symptoms after deployment relative to matched
      comparison subjects. Logistic regression analysis showed that the risk for
      inclusion in the PTSD group after deployment increased 7.5-fold with each GR
      increase of 1,000. No group differences were observed in mRNA expression of GR
      alpha, GR-P, GR-beta, glucocorticoid-induced leucine zipper (GILZ), serum and
      glucocorticoid-inducible kinase-1 (SGK-1), and FKBP5. The higher GR number in the
      PTSD group was maintained at 1 and 6 months after deployment. CONCLUSIONS: These
      results demonstrate that a preexisting high GR number in PBMCs is a vulnerability
      factor for subsequent development of PTSD symptoms.

PMID- 21078708
TI  - Aberrant brain activation during a working memory task in psychotic major
      depression.
AB  - OBJECTIVE: The authors sought to better understand the neural circuitry
      associated with working memory deficits in psychotic major depression by
      examining brain function during an N-back task. METHOD: Study subjects were 16
      patients with psychotic major depression, 15 patients with nonpsychotic major
      depression, and 19 healthy comparison subjects. Functional MRI data were
      collected while participants responded to letter stimuli that were repeated from
      the previous trial (1-back) or the one before that (2-back). RESULTS: Relative to
      the healthy comparison group, both the psychotic and nonpsychotic major
      depression groups had significantly greater activation in the right
      parahippocampal gyrus during the 2-back task, and the psychotic major depression
      group showed this overactivation during the 1-back task as well. The nonpsychotic
      major depression group showed significantly lower activation than other groups in
      the right dorsolateral prefrontal cortex and greater activation than the healthy
      comparison group in the superior occipital cortex. The psychotic major depression
      group was unique in showing greater activation than both other groups in the
      right temporoparietal junction, a cluster that also demonstrated connectivity
      with activation in the left prefrontal cortex. CONCLUSIONS: The psychotic major
      depression group showed aberrant parahippocampal activation at a lower demand
      level than observed in nonpsychotic major depression. While the nonpsychotic
      major depression group showed abnormalities in frontal executive regions, the
      psychotic major depression group showed abnormalities in temporoparietal regions
      associated with orienting to unexpected stimuli. Considering the functional
      connectivity of this cluster with left dorsolateral prefrontal cortex regions,
      these findings may reflect neural compensation for sensory gating deficits in
      psychotic major depression.

PMID- 21078707
TI  - Disrupted reinforcement signaling in the orbitofrontal cortex and caudate in
      youths with conduct disorder or oppositional defiant disorder and a high level of
      psychopathic traits.
AB  - OBJECTIVE: Dysfunction in the amygdala and orbitofrontal cortex has been reported
      in youths and adults with psychopathic traits. The specific nature of the
      functional irregularities within these structures remains poorly understood. The
      authors used a passive avoidance task to examine the responsiveness of these
      systems to early stimulus-reinforcement exposure, when prediction errors are
      greatest and learning maximized, and to reward in youths with psychopathic traits
      and comparison youths. METHOD: While performing the passive avoidance learning
      task, 15 youths with conduct disorder or oppositional defiant disorder plus a
      high level of psychopathic traits and 15 healthy subjects completed a 3.0-T fMRI
      scan. RESULTS: Relative to the comparison youths, the youths with a disruptive
      behavior disorder plus psychopathic traits showed less orbitofrontal
      responsiveness both to early stimulus-reinforcement exposure and to rewards, as
      well as less caudate response to early stimulus-reinforcement exposure. There
      were no group differences in amygdala responsiveness to these two task measures,
      but amygdala responsiveness throughout the task was lower in the youths with
      psychopathic traits. CONCLUSIONS: Compromised sensitivity to early reinforcement
      information in the orbitofrontal cortex and caudate and to reward outcome
      information in the orbitofrontal cortex of youths with conduct disorder or
      oppositional defiant disorder plus psychopathic traits suggests that the
      integrated functioning of the amygdala, caudate, and orbitofrontal cortex may be
      disrupted. This provides a functional neural basis for why such youths are more
      likely to repeat disadvantageous decisions. New treatment possibilities are
      raised, as pharmacologic modulations of serotonin and dopamine can affect this
      form of learning.

PMID- 21078709
TI  - Subthreshold hypomanic symptoms in progression from unipolar major depression to
      bipolar disorder.
AB  - OBJECTIVE: The authors assessed whether subthreshold hypomanic symptoms in
      patients with major depression predicted new-onset mania or hypomania. METHOD:
      The authors identified 550 individuals followed for at least 1 year in the
      National Institute of Mental Health Collaborative Depression Study with a
      diagnosis of major depression at intake. All participants were screened at
      baseline for five manic symptoms: elevated mood, decreased need for sleep,
      unusually high energy, increased goal-directed activity, and grandiosity.
      Participants were followed prospectively for a mean of 17.5 years and up to 31
      years. The Longitudinal Interval Follow-up Examination was used to monitor course
      of illness and to identify any hypomania or mania. The association of
      subthreshold hypomanic symptoms at baseline with subsequent hypomania or mania
      was determined in survival analyses using Cox proportional hazards regression.
      RESULTS: With a cumulative probability of one in four on survival analysis, 19.6%
      (N=108) of the sample experienced hypomania or mania, resulting in revision of
      diagnoses for 12.2% to bipolar II disorder and 7.5% to bipolar I disorder. Number
      of subthreshold hypomanic symptoms, presence of psychosis, and age at illness
      onset predicted progression to bipolar disorder. Decreased need for sleep,
      unusually high energy, and increased goal-directed activity were specifically
      implicated. CONCLUSIONS: Symptoms of hypomania, even when of low intensity, were
      frequently associated with subsequent progression to bipolar disorder, although
      the majority of patients who converted did not have any symptoms of hypomania at
      baseline. These results suggest that continued monitoring for the possibility of
      progression to bipolar disorder is necessary over the long-term course of major
      depressive disorder.

PMID- 21078710
TI  - A randomized controlled trial of the cost-effectiveness of ultrasound-guided
      intraarticular injection of inflammatory arthritis.
AB  - OBJECTIVE: We studied whether sonographic needle guidance affected the outcomes
      of intraarticular (IA) injection for inflammatory arthritis. METHODS: Joints with
      inflammatory arthritis (n = 244; 76% rheumatoid arthritis, 3% small joints, 51%
      intermediate, and 46% large) were randomized to injection by conventional
      palpation-guided anatomic injection (120 joints) or sonographic image-guided
      injection enhanced with a 1-handed reciprocating procedure device mechanical
      syringe (124 joints). A 1-needle, 2-syringe technique was used. After IA
      placement and synovial space dilation were confirmed by sonography, a syringe
      exchange was performed, and triamcinolone acetonide was injected with the second
      syringe through the indwelling IA needle. Baseline pain, procedural pain, pain at
      outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection
      rates, total cost, and cost per responder were determined. RESULTS: Relative to
      conventional palpation-guided methods, sonographic guidance for injection of
      inflammatory arthritis resulted in an 81% reduction in injection pain (p <
      0.001), 35% reduction in pain scores at outcome (p < 0.02), 38% increase in the
      responder rate (p < 0.003), 34% reduction in the non-responder rate (p < 0.003),
      32% increase in therapeutic duration (p = 0.01), 8% reduction ($7) in
      cost/patient/year, and a 33% ($64) reduction in cost/responder/year for a
      hospital outpatient (p < 0.001). CONCLUSION: Sonographic needle guidance improves
      the performance, clinical outcomes, and cost-effectiveness of IA injections for
      inflammatory arthritis. (Clinical Trial Identifier NCT00651625).

PMID- 21078711
TI  - Disease phenotypes and gender association of FCRL3 single-nucleotide polymorphism
      -169T/C in Taiwanese patients with systemic lupus erythematosus and rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the association of the functional FCRL3 single
      nucleotide polymorphism (SNP) -169T/C with disease phenotypes and susceptibility
      to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese.
      METHODS: FCRL3 SNP -169T/C was genotyped in 573 patients with SLE, 670 patients
      with RA, and 758 controls. Genotype distributions and allele frequencies were
      compared among the 3 groups as aggregates or as stratified by clinical
      characteristics, autoantibody profile, and sex within patient groups. RESULTS:
      Overall, FCRL3 SNP -169T/C was not associated with susceptibility to either SLE
      or RA. However, -169CC genotype was significantly reduced in leukopenia-positive
      SLE patients as compared to the leukopenia-negative SLE patients (CC vs CT+TT, p
      = 6 * 10(-4), OR 0.444, 95% CI 0.279-0.708) and controls (p = 6.1 * 10(-3), OR
      0.583, 95% CI 0.396-0.857). On the other hand, -169TT genotypes were
      significantly more numerous in RA patients with non-destructive disease as
      compared with patients with destructive disease (CC+CT vs TT: p = 0.007, OR
      1.672, 95% CI 1.149-2.432). The -169T allele frequency was also significantly
      increased in non-destructive RA compared with patients with destructive disease
      (C vs T: p = 0.010, OR 1.423, 95% CI 1.089-1.859). FCRL3 SNP -169TT homozygous
      donors were significantly more numerous among female cyclic citrullinated peptide
      (CCP)-negative RA patients versus female CCP-positive RA patients (CC+CT vs TT: p
      = 0.019, OR 1.64, 95% CI 1.085-2.479). CONCLUSION: The functional FCRL3 SNP 
      169T/C appears to play important roles in the development of certain phenotypes
      such as SLE leukopenia and RA disease severity in Taiwanese patients with SLE and
      RA.

PMID- 21078712
TI  - A new presentation of neonatal lupus: 5 cases of isolated mild endocardial
      fibroelastosis associated with maternal Anti-SSA/Ro and Anti-SSB/La antibodies.
AB  - OBJECTIVE: Maternal anti-SSA/Ro or anti-SSB/La antibodies are associated with
      neonatal lupus erythematosus syndrome (NLES), especially congenital heart block
      (CHB), which may be associated with severe endocardial fibroelastosis (EFE) and
      dilated cardiomyopathy (DCM). A few reports have described severe EFE without CHB
      associated with anti-SSA/Ro antibodies, with a poor prognosis. EFE has also been
      observed in biopsies of DCM that had been considered idiopathic. These points,
      considered in association with 5 unusual cases of mild EFE, led us to consider
      the relationship between underrecognized cases of isolated autoantibody
      associated EFE and DCM that had been considered idiopathic. METHODS: We analyzed
      5 cases of EFE diagnosed in utero (n = 4) or after birth (n = 1). In 3 cases,
      maternal antibody status was discovered because of the EFE diagnosis. RESULTS:
      Endomyocardial hyperechogenicity predominated in the left atrium (n = 3) and
      mitral annulus (n = 3). No left-heart dysfunction was observed. Two mothers were
      treated with betamethasone. One mother chose to have a therapeutic abortion, and
      EFE was confirmed at autopsy. Electrocardiograms at birth (n = 4) did not show
      CHB. Other manifestations of NLES were present in all cases. One child had right
      ventricular hypoplasia and underwent a partial cavopulmonary anastomosis. At last
      followup (4-7 yrs), the other 3 children had normal heart function, and
      echocardiography showed a normal heart (n = 2) or mild persistent EFE (n = 1).
      CONCLUSION: Middle-term prognosis of isolated autoantibody-associated EFE may be
      better than previously reported, although the longterm prognosis remains unknown.
      We hypothesize that a fetal insult can lead to DCM.

PMID- 21078713
TI  - Low body mass index is adversely associated with radiographic joint damage in
      Indian patients with early rheumatoid arthritis.
AB  - OBJECTIVE: Various factors affect joint damage in rheumatoid arthritis (RA). The
      influence of body mass index (BMI) is not adequately known. As BMI is potentially
      modifiable, we studied its influence on radiological joint damage in patients
      with RA. METHODS: Treatment-naive patients with early RA (< 24 mo) were included.
      Demographic data were collected along with swollen joint count (SJC), tender
      joint count (TJC), erythrocyte sedimentation rate (ESR), and IgM-rheumatoid
      factor (IgM-RF). Radiographs of hands and feet were obtained. BMI and Disease
      Activity Score for 28-joint count (DAS28-ESR) were calculated. Joint damage was
      assessed using the Simplified Erosions Narrowing Score (SENS). RESULTS: A total
      of 101 patients were studied (81 women; mean age 41.91 +/- 11.99 yrs). Mean
      disease duration was 10.77 +/- 6.73 months; 55 patients (54.5%) were IgM-RF
      positive. Mean BMI was 22.82 +/- 4.66 kg/m(2) with 24 (23.8%) patients having
      low, 42 (41.6%) normal, and 35 (34.7%) high BMI. Mean SENS score was 16.81 +/-
      11.10; mean DAS28 was 6.23 +/- 0.96. Significant correlation was noted between
      SENS and DAS28 (r = 0.28; p < 0.005). There was significant negative correlation
      between BMI and SENS (r = -0.509; p < 0.0005). In patients with low BMI, mean
      SENS (26.62 +/- 13.45) was significantly higher than in patients with normal
      (15.88 +/- 8.38; p < 0.001) and high BMI (11.20 +/- 7.32; p < 0.001). Patients
      with normal BMI also had significantly higher SENS scores than those with high
      BMI (p < 0.05). One-way ANOVA did not reveal significant differences in DAS28
      between groups. SENS was significantly higher in the IgM-RF-positive group (19.55
      +/- 11.36) than in the IgM-RF-negative group (13.54 +/- 9.94; p < 0.01); DAS28
      was not different between the 2 groups (6.22 +/- 0.98 vs 6.26 +/- 0.96,
      respectively). Within the 2 IgM-RF groups, a significant negative correlation was
      seen between BMI and SENS. Multiple regression analysis revealed RF, DAS28, and
      BMI were independently associated with SENS. BMI accounted for 23.04% of the
      variance in SENS independent of DAS28 and IgM-RF. CONCLUSION: Low BMI is
      adversely associated with joint damage in patients with early RA.

PMID- 21078714
TI  - Quantification of cells expressing mesenchymal stem cell markers in healthy and
      osteoarthritic synovial membranes.
AB  - OBJECTIVE: To quantify cells expressing mesenchymal stem cell (MSC) markers in
      synovial membranes from human osteoarthritic (OA) and healthy joints. METHODS:
      Synovial membranes from OA and healthy joints were digested with collagenase and
      the isolated cells were cultured. Synovial membrane-derived cells were
      phenotypically characterized for differentiation experiments using flow cytometry
      to detect the expression of mesenchymal markers (CD29, CD44, CD73, CD90, CD105,
      CD117, CD166, and STRO-1) and hematopoietic markers (CD34 and CD45).
      Chondrogenesis was assessed by staining for proteoglycans and collagen type II,
      adipogenesis by using a stain for lipids, and osteogenesis by detecting calcium
      deposits. Coexpression of CD44, CD73, CD90, and CD105 was determined using
      immunofluorescence. RESULTS: Cells expressing MSC markers were diffusely
      distributed in OA synovial membranes; in healthy synovial membrane these cells
      were localized in the subintimal zone. More numerous MSC markers in OA synovial
      membranes were observed in cells also expressing the CD90 antigen. FACS analysis
      showed that more than 90% of OA synovial membrane-derived cells were positive for
      CD44, CD73, and CD90, and negative for CD34 and CD45. OA synovial membrane
      derived cells were also positive for CD29 (85.23%), CD117 (72.35%), CD105
      (45.5%), and STRO-1 (49.46%). Micropellet analyses showed that the culture of
      cells with transforming growth factor-beta3 stimulated proteoglycan and collagen
      type II synthesis. CONCLUSION: Synovial membranes from patients with OA contain
      more cells positive for CD44, CD90, and CD105 antigens than those from joints
      with undamaged cartilage.

PMID- 21078715
TI  - Factors associated with radiographic progression in patients with rheumatoid
      arthritis who were treated with methotrexate.
AB  - OBJECTIVE: To identify factors associated with radiographic progression at 52
      weeks in patients with rheumatoid arthritis (RA) after 12 weeks of methotrexate
      (MTX) therapy. METHODS: The study population consisted of patients from the MTX
      arm of the Trial of Etanercept and Methotrexate with Radiographic Patient
      Outcomes (TEMPO). Logistic regression analysis was used to identify clinical and
      laboratory assessments performed at Week 12 of MTX therapy that might be
      associated with Week 52 radiographic outcome (modified total Sharp score).
      Classification and regression tree (CART) modeling of the Week 12 assessments was
      used to determine the subgroups of patients with the best and worst radiographic
      outcomes. RESULTS: A total of 169 patients were analyzed: 116 patients in the
      best radiographic outcome group and 53 patients in the worst radiographic outcome
      group. Logistic regression analysis showed that Week 12 C-reactive protein (CRP)
      level, erythrocyte sedimentation rate, tender joint count, swollen joint count
      (SJC), and Health Assessment Questionnaire scores were significantly associated
      with radiographic progression at Week 52 (p < 0.05 for each assessment). CART
      modeling showed that patients with Week 12 CRP > 0.67 mg/dl and SJC > 1 and
      patients with Week 12 CRP <= 0.67 mg/dl and SJC > 10 were likely to show the
      worst radiographic progression at Week 52. The CART model had a sensitivity of
      85%, specificity of 60%, and overall classification accuracy of 68%. CONCLUSION:
      In patients with RA, measures of CRP and SJC after 12 weeks of MTX therapy
      emerged as the factors most associated with radiographic progression at Week 52.

PMID- 21078716
TI  - Progressive loss of lymphatic vessels in skin of patients with systemic
      sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disorder characterized
      by microvascular and fibrotic changes in the skin and internal organs. The role
      of blood vessel dysfunction in the pathogenesis of SSc has been extensively
      investigated, but few studies have addressed the involvement of the lymphatic
      vascular system. Our aim was to evaluate dermal lymphatic vessels in patients
      with SSc according to different phases of skin involvement. METHODS: Skin
      biopsies were obtained from the forearm of 25 SSc patients (10 early/15 late
      stage disease) and 13 healthy controls. Skin sections were immunostained for
      podoplanin (D2-40), which is selectively expressed in lymphatic endothelial
      cells, and examined by confocal laser scanning microscopy. Lymphatic vessels were
      counted in the papillary and reticular dermis. Data were analyzed using Student's
      t test. RESULTS: The number of lymphatic vessels was significantly reduced in the
      papillary and reticular dermis of SSc patients compared with controls. In early
      SSc, lymphatic vessel counts were not different from controls in the papillary
      dermis, and showed a trend toward a reduction in the reticular dermis. In late
      SSc, a significant reduction in lymphatic vessels compared with controls was
      found in both the papillary and reticular dermis. The number of lymphatic vessels
      in the papillary dermis of late SSc was significantly lower than in early SSc.
      CONCLUSION: In SSc, lymphatic microangiopathy is linked to the progression of
      skin involvement. The progressive disappearance of lymphatic vessels may have a
      critical pathogenetic role in the progression of SSc from an early edematous
      phase to overt fibrosis.

PMID- 21078717
TI  - Use of nonsteroidal antiinflammatory drugs: is there a change in patient risk
      profile after withdrawal of rofecoxib?
AB  - OBJECTIVE: Use of traditional nonsteroidal antiinflammatory drugs (tNSAID)
      increased after rofecoxib withdrawal. tNSAID use is associated with increased
      gastrointestinal (GI) toxicity and cardiovascular (CV) risk similar to celecoxib.
      The objective of our study was to describe changes in celecoxib and tNSAID use
      regarding GI and CV risk and congestive heart failure (CHF) and renal risk that
      occurred in Quebec, Canada, between April 2005-March 2007 (the post-period)
      compared to April 2002-March 2004 (the pre-period). METHODS: Data were obtained
      from the provincial health insurance agency. All NSAID users >= 50 years of age
      were considered. RESULTS: Celecoxib use decreased by 23% (coxib 61%) while that
      of tNSAID doubled. In both periods, celecoxib users were older and included more
      women, and they suffered more frequently from arthritis. Users of celecoxib were
      more likely to have higher level of GI risk: post-period odds ratios compared to
      low GI risk, very high 1.79 (95% CI 1.63, 1.97), high 1.76 (95% CI 1.71, 1.81),
      and moderate 1.30 (95% CI 1.27, 1.33); similar results were observed in the pre
      period. Celecoxib users had higher CV risk levels in the pre-period: OR compared
      to low CV risk, very high 1.13 (95% CI 1.08, 1.19), high 1.24 (95% CI 1.20,
      1.29), and moderate 1.16 (95% CI 1.14, 1.19); and in the post-period, very high
      0.85 (95% CI 0.81, 0.89), high 1.13 (95% CI 1.10, 1.16), and moderate 1.15 (95%
      CI 1.12, 1.17). CHF and renal risk factors did not play an important role in the
      choice of NSAID in either period. CONCLUSION: Current NSAID use differs from that
      prior to 2004. Coxib utilization decreased substantially and patients at high CV
      risk seem less likely to receive celecoxib, while those at high GI risk seem more
      likely to receive it.

PMID- 21078718
TI  - Optimal frequency of visits for patients with systemic lupus erythematosus to
      measure disease activity over time.
AB  - OBJECTIVE: adjusted mean Systemic Lupus Erythematosus Disease Activity Index
      (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine
      optimal visit frequency for calculating AMS. METHODS: patients followed monthly
      for 12 consecutive visits were included. AMS was calculated using all of the
      SLEDAI 2000 (AMS(GOLD) using all 12 visits), only quarterly visits (AMS(3), using
      visits 3 months apart), semiannual visits (AMS(6), using first, middle, and last
      visits only), and annual visits (AMS(12), using only the first and last visits).
      Comparisons of AMS(3), AMS(6), and AMS(12) with AMS(GOLD) are made using
      descriptive statistics. RESULTS: seventy-eight patients were included (92% women,
      mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD)
      AMS(GOLD) for the entire year was 2.05 (1.66), for AMS(3) 1.99 (1.65), for AMS(6)
      2.12 (1.87), and for AMS(12) 2.08 (1.83). Mean (SD) of the absolute differences
      with AMS(GOLD): for AMS(3) 0.29 (0.33), for AMS(6) 0.45 (0.59), and for AMS(12)
      0.61 (0.58). Differences that were < 0.5 were considered minimal while those >= 1
      were deemed important. Comparing AMS(GOLD) to AMS(3), 82% of the differences were
      minimal and 3% were important. When comparing to AMS(6), 68% were minimal and 10%
      were important, while comparing to AMS(12), 50% were minimal and 21% were
      important. CONCLUSION: usual clinic visits occurring quarterly offer a good
      estimation of disease activity over a 1-year period and are preferred over
      semiannual and annual visits.

PMID- 21078719
TI  - ERAP1 is associated with ankylosing spondylitis in Han Chinese.
AB  - OBJECTIVE: Genetic components play important roles in the incidence and
      development of ankylosing spondylitis (AS). Aminopeptidase regulator of tumor
      necrosis factor receptor shedding 1 (ERAP1) was recently found to be associated
      with AS in North American and British cohorts. We evaluated whether ERAP1 is
      associated with AS in a Chinese Han population. METHODS: A sample of 50 patients
      and 50 healthy controls was recruited for preliminary screening for informative
      single-nucleotide polymorphisms (SNP). Then 6 SNP of suggestive significance in
      the initial screening were followed up in a large sample of 471 patients with AS
      and 456 ethnically matched controls. Diagnosis of AS followed the 1984 modified
      New York criteria. Linkage disequilibrium coefficient (D' and r(2)) and
      haplotypes were estimated by Haploview. Result. Two SNP (rs27434, p = 0.00039,
      and rs27529, p = 0.0083) in ERAP1 other than that reported previously were found
      to be significantly associated with AS. Haplotype analysis using 5 SNP within 1
      linkage disequilibrium block identified 2 risk haplotypes (GATGT and GACGT) and 1
      protective haplotype (GGTGT) for AS. CONCLUSION: Our study demonstrated that 2
      novel SNP in ERAP1 were associated with AS in the Han Chinese population,
      suggesting that ERAP1 might confer genetic risk for AS in Han Chinese through the
      common mechanism shared by different populations, although the AS-associated SNP
      in ERAP1 might be population-specific.

PMID- 21078720
TI  - Improvement of thyroid function in hypothyroid patients with rheumatoid arthritis
      after 6 months of adalimumab treatment: a pilot study.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by high levels of cytokines
      such as tumor necrosis factor (TNF). TNF appears to have an etiologic role in
      thyroid dysfunction, and thyroid dysfunction is a common comorbidity in RA. Anti
      TNF treatment might limit thyroid dysfunction. Thus, changes in thyroid hormones
      were studied during TNF-blocking therapy in patients with RA. METHODS: At
      baseline and after 6 months' treatment with adalimumab, thyroid function [thyroid
      stimulating hormone (TSH), free thyroxine (fT4), and antibodies against thyroid
      peroxidase (TPOabs)] were assessed in 138 consecutive adalimumab-treated patients
      with RA who were naive for TNF-blocking agents. Patients were categorized as
      hypothyroid, hyperthyroid, or euthyroid. In these groups, changes in thyroid
      function were determined. RESULTS: Prevalences of hypothyroidism,
      hyperthyroidism, and TPOabs were 13%, 5%, and 15%, respectively. After 6 months,
      TPOabs decreased from 267 to 201 IU/ml (p = 0.048). In hypothyroid patients
      without concomitant L-thyroxine, a trend for declining levels of TSH was
      observed. Subgroup analysis revealed that in patients who were hypothyroid and
      TPOabs-positive and L-thyroxine-naive, TSH levels decreased significantly, from
      12.5 (interquartile range 6.7-18.4) to 7.1 (interquartile range 4.9-13.8) mU/l (p
      = 0.043). CONCLUSION: Anti-TNF treatment improves thyroid function in hypothyroid
      patients with RA (especially in those who are L-thyroxine-naive and TPOabs
      positive), providing further evidence that inflammatory cytokines such as TNF
      have a pathogenic role in thyroid dysfunction.

PMID- 21078721
TI  - Effect of sociodemographic factors on surgical consultations and hip or knee
      replacements among patients with osteoarthritis in British Columbia, Canada.
AB  - OBJECTIVE: To quantify the effect of demographic variables and socioeconomic
      status (SES) on surgical consultation and total joint arthroplasty (TJA) rates
      among patients with osteoarthritis (OA), using population-based administrative
      data. METHODS: A cohort study was conducted in British Columbia using population
      data from 1991 to 2004. From April 1996 to March 1998, we documented 34,420 new
      patients with OA and these patients were followed to March 2004 for their first
      surgical consultation and TJA. Effects of age, sex, and SES were evaluated by Cox
      proportional hazards models after adjusting for comorbidities and pain medication
      used. RESULTS: During a mean 5.5-year followup period, 7475 patients with OA had
      their first surgical consultations and 2814 patients received TJA within a 6-year
      mean followup period. Crude hazards ratio (HR) for men compared to women was 1.25
      (95% CI 1.20-1.31) for surgical consultation and was 1.14 (95% CI 1.06-1.23) for
      TJA. The interaction between sex and SES was significant. Stratified analysis
      showed among men an HR of 1.42 (95% CI 1.27-1.58) and 1.52 (95% CI 1.26-1.83) for
      surgical consultations and TJA, respectively, for the highest SES compared with
      the lowest SES quintiles. Similarly significant results were observed among
      women. CONCLUSION: Differential access to the healthcare system exists among
      patients with OA. Women with OA were less likely than men to see an orthopedic
      surgeon as well as to obtain TJA. Patients with higher SES consulted orthopedic
      surgeons more frequently and received more TJA than those with the lowest SES.

PMID- 21078722
TI  - Medication use in systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate factors affecting therapeutic approaches used in clinical
      practice for the management of systemic lupus erythematosus (SLE), in a
      multicenter cohort. METHODS: We combined data from 10 clinical adult SLE cohort
      registries in Canada. We used multivariate generalized estimating equation
      methods to model dichotomized outcomes, running separate regressions where the
      outcome was current exposure of the patient to specific medications. Potential
      predictors of medication use included demographic (baseline age, sex, residence,
      race/ethnicity) and clinical factors (disease duration, time-dependent damage
      index scores, and adjusted mean SLE Disease Activity Index-2K scores). The models
      also adjusted for clustering by center. RESULTS: Higher disease activity and
      damage scores were each independent predictors of exposure to nonsteroid
      immunosuppressive agents, and for exposure to prednisone. This was not definitely
      demonstrated for antimalarial agents. Older age at diagnosis was independently
      and inversely associated with exposure to any of the agents studied
      (immunosuppressive agents, prednisone, and antimalarial agents). An additional
      independent predictor of prednisone exposure was black race/ethnicity (adjusted
      RR 1.46, 95% CI 1.18, 1.81). For immunosuppressive exposure, an additional
      independent predictor was race/ethnicity, with greater exposure among Asians (RR
      1.39, 95% CI 1.02, 1.89) and persons identifying themselves as First
      Nations/Inuit (2.09, 95% CI 1.43, 3.04) than among whites. All of these findings
      were reproduced when adjustment for disease activity was limited to renal
      involvement. CONCLUSION: Ours is the first portrayal of determinants of clinical
      practice patterns in SLE, and offers interesting real-world insights. Further
      work, including efforts to determine how differing clinical approaches may
      influence outcome, is in progress.

PMID- 21078723
TI  - Cardiovascular disease is related to hypertension in patients with rheumatoid
      arthritis: a greek cohort study.
AB  - OBJECTIVE: To evaluate the incidence of cardiovascular disease (CVD) among Greek
      patients with rheumatoid arthritis (RA) under medical followup, and to assess the
      contribution of traditional CVD and RA-specific factors associated with CVD
      development. METHODS: This is a historic cohort study; information was collected
      from medical records of patients who had > 2 years' followup. Sociodemographic,
      clinical, laboratory, and therapeutic variables were evaluated for association
      with development of CVD. RESULTS: A total of 325 RA patients were studied: 250
      women, mean age at RA onset 44 +/- 15 years, and 75 men, mean age at RA onset 51
      +/- 15 years; median followup was 10 years. Fourteen women (5.6%) and 12 men
      (16%) developed CVD (p = 0.004). Multi-adjusted analysis revealed that
      hypertension (hazard ratio 3.76, 95% CI 0.99-15.06) was associated with incidence
      of CVD; late age at disease onset (HR 1.07, 95% CI 1.04-1.11), elevated C
      reactive protein (CRP) level 1 year after start of followup (HR 1.03, 95% CI 1.00
      1.05), and leflunomide treatment (HR per 1 year of treatment = 1.02, 95% CI 1.00
      1.05) were also positively associated with CVD development. CONCLUSION:
      Hypertension was an important risk factor for CVD development in patients with
      RA. Late RA onset and inadequate early control of disease activity (as attested
      by CRP) remain additional risk factors. Leflunomide treatment may have a
      contributing effect. Early and effective treatment of RA and strict control of
      hypertension may modify the burden of CVD in RA patients.

PMID- 21078724
TI  - Pediatric Behcet's disease and thromboses.
AB  - OBJECTIVE: To describe the characteristics of a group of pediatric patients with
      Behcet's disease (BD) who presented at least 1 episode of thrombosis during their
      disease course. METHODS: We made a retrospective chart review of the clinical,
      biological, and radiological data of children with BD who presented at least 1
      episode of either arterial or venous thrombosis. Data were extracted from both an
      international pediatric Behcet cohort and files referred from 7 French centers.
      RESULTS: Twenty-one patients were included. Diagnosis of BD was based on the
      criteria of the International Study Group for BD. Main locations for thrombosis
      were the cerebral sinuses, in 11 patients (52.4%); and lower limbs, in 9 patients
      (40.9%). Recurrent episodes were observed in 4 patients (21%). Thrombophilia
      measurements were normal in 14 patients out of 21, while anticardiolipin
      antibodies were positive in 4 patients, and 2 out of 21 had protein C deficiency.
      One patient had lupus anticoagulant. All patients were treated with colchicine.
      Corticosteroids were also added for variable periods in 13 patients. Five
      patients out of 21 were treated with anticoagulants (heparin, then anti-vitamin
      K) and 3 with antiplatelets (acetylsalicylic acid). CONCLUSION: Thromboses are a
      serious complication of BD and may occur early in the disease course. The
      presence of thrombophilic markers could increase the risk of thrombosis in BD,
      but the size of our population does not allow any conclusion. An international
      cohort (PED-BD) is currently in place and will allow study of such cases
      longitudinally, as well as assessment of the elements that correlate with an
      increased risk of thrombosis in children with BD.

PMID- 21078725
TI  - Activation of the interferon pathway in peripheral blood of patients with
      Sjogren's syndrome.
AB  - OBJECTIVE: DNA microarray analysis and quantitative real-time polymerase chain
      reaction (PCR) were performed to identify key target genes in peripheral blood
      from patients with Sjogren's syndrome (SS). METHODS: DNA microarray analysis was
      performed in 19 patients with SS (all women) and 10 healthy controls (5 men and 5
      women) using a low-density DNA microarray system with 778 genes. For
      confirmation, the expression of upregulated genes was analyzed by quantitative
      real-time PCR in another 37 SS patients (35 women and 2 men) and 9 healthy
      controls (8 women and 1 man). Relationships between gene signatures and various
      clinical measures, such as disease duration, symptoms and signs, complications,
      immunological findings, and salivary and lacrimal functions, were analyzed.
      RESULTS: Interferon-alpha (IFN-alpha)-inducible protein 27 (IFI27) showed the
      most significant difference between SS patients and controls in the microarray
      screening. We performed quantitative RT-PCR for IFI27. IFI27 gene expression
      level was increased in patients with SS compared with controls (p < 0.01) by real
      time PCR, supporting our observations from the microarray data. The level of
      IFI27 was significantly correlated with serum IgG levels (r = 0.462, p < 0.01)
      and beta(2)-microglobulin (r = 0.385, p < 0.05), soluble interleukin 2 receptor
      (r = 0.473, p < 0.01), erythrocyte sedimentation rate (r = 0.333, p < 0.05), and
      antinuclear antibody titer (speckled pattern; r = 0.445, p < 0.01). CONCLUSION:
      Our results suggest that upregulation of IFN-inducible genes in SS patients is a
      systemic phenomenon, and IFN may play an important role in the pathogenesis of
      SS. The expression level of IFI27 could be an effective and specific biomarker
      associated with SS.

PMID- 21078726
TI  - Youth motorcycle-related brain injury by state helmet law type: United States,
      2005-2007.
AB  - BACKGROUND AND OBJECTIVES: Twenty-seven states have youth-specific helmet laws
      even though such laws have been shown to decrease helmet use and increase youth
      mortality compared with all-age (universal) laws. Our goal was to quantify the
      impact of age-specific helmet laws on youth under age 20 hospitalized with
      traumatic brain injury (TBI). METHODS: Our cross-sectional ecological group
      analysis compared TBI proportions among US states with different helmet laws. We
      examined the following null hypothesis: If age-specific helmet laws are as
      effective as universal laws, there will be no difference in the proportion of
      hospitalized young motorcycle riders with TBI in the respective states. The data
      are derived from the 2005 to 2007 State Inpatient Databases of the Healthcare
      Cost and Utilization Project. We examined data for 17 states with universal laws,
      6 states with laws for ages <21, and 12 states with laws for children younger
      than 18 (9287 motorcycle injury discharges). RESULTS: In states with a <21 law,
      serious TBI among youth was 38% higher than in universal-law states. Motorcycle
      riders aged 12 to 17 in 18 helmet-law states had a higher proportion of
      serious/severe TBI and higher average Abbreviated Injury Scores for head-region
      injuries than riders from universal-law states. CONCLUSIONS: States with youth
      specific laws had an increased risk of TBI that required hospitalization, serious
      and severe TBI, TBI-related disability, and in-hospital death among the youth
      they are supposed to protect. The only method known to keep motorcycle-helmet use
      high among youth is to adopt or maintain universal helmet laws.

PMID- 21078727
TI  - Trends in cause-specific mortality at a Canadian outborn NICU.
AB  - OBJECTIVE: To retrospectively review changes in the causes of death of infants
      dying in the NICU at Canada's largest outborn pediatric center. PATIENTS AND
      METHODS: All inpatient deaths at the Hospital for Sick Children's NICU that
      occurred in the years 1997, 2002, and 2007 were retrospectively reviewed to
      identify the primary cause of death. Classification of the cause of death was
      based on a modified version of the Perinatal Society of Australia and New
      Zealand's Neonatal Death Classification. RESULTS: The annual mortality rate
      remained relatively constant (average of 7.6 deaths per 100 admissions between
      1988 and 2007). A total of 156 deaths were analyzed: 53 in 1997; 50 in 2002; and
      53 in 2007. The chronological age at which premature infants died increased
      significantly over the 3 time periods (P = .01). The proportion of deaths
      attributable to extreme prematurity and intraventricular hemorrhage decreased
      over the study period, whereas the proportion of deaths attributed to
      gastrointestinal causes (specifically necrotizing enterocolitis and focal
      intestinal perforation) increased. The proportion of infants for whom there was a
      decision to limit care before death was stable at between 83% and 92%.
      CONCLUSIONS: A larger proportion of outborn premature infants admitted to the
      Hospital for Sick Children's NICU seem to be surviving the early problems of
      prematurity only to succumb to late complications.

PMID- 21078728
TI  - Variability in antibiotic use at children's hospitals.
AB  - BACKGROUND: Variation in medical practice has identified opportunities for
      quality improvement in patient care. The degree of variation in the use of
      antibiotics in children's hospitals is unknown. METHODS: We conducted a
      retrospective cohort study of 556,692 consecutive pediatric inpatient discharges
      from 40 freestanding children's hospitals between January 1, 2008, and December
      31, 2008. We used the Pediatric Health Information System to acquire data on
      antibiotic use and clinical diagnoses. RESULTS: Overall, 60% of the children
      received at least 1 antibiotic agent during their hospitalization, including >90%
      of patients who had surgery, underwent central venous catheter placement, had
      prolonged ventilation, or remained in the hospital for >14 days. Even after
      adjustment for both hospital- and patient-level demographic and clinical
      characteristics, antibiotic use varied substantially across hospitals, including
      both the proportion of children exposed to antibiotics (38%-72%) and the number
      of days children received antibiotics (368-601 antibiotic-days per 1000 patient
      days). In general, hospitals that used more antibiotics also used a higher
      proportion of broad-spectrum antibiotics. CONCLUSIONS: Children's hospitals vary
      substantially in their use of antibiotics to a degree unexplained by patient- or
      hospital-level factors typically associated with the need for antibiotic therapy,
      which reveals an opportunity to improve the use of these drugs.

PMID- 21078729
TI  - Video-gaming among high school students: health correlates, gender differences,
      and problematic gaming.
AB  - OBJECTIVE: Video game playing may negatively impact youth. However, the existing
      literature on gaming is inconsistent and often has focused on aggression rather
      than the health correlates of gaming and the prevalence and correlates of
      problematic gaming. METHODS: We anonymously surveyed 4028 adolescents about
      gaming and reported problems with gaming and other health behaviors. A total of
      51.2% of the sample reported gaming (76.3% of boys and 29.2% of girls). RESULTS:
      There were no negative health correlates of gaming in boys and lower odds of
      smoking regularly; however, girls who reported gaming were less likely to report
      depression and more likely to report getting into serious fights and carrying a
      weapon to school. Among gamers, 4.9% reported problematic gaming, defined as
      reporting trying to cut back, experiencing an irresistible urge to play, and
      experiencing a growing tension that could only be relieved by playing. Boys were
      more likely to report these problems (5.8%) than girls (3.0%). Correlates of
      problematic gaming included regular cigarette smoking, drug use, depression, and
      serious fights. Results suggest that gaming is largely normative in boys and not
      associated with many health factors. In girls, however, gaming seems to be
      associated with more externalizing behaviors and fewer internalizing symptoms.
      CONCLUSIONS: The prevalence of problematic gaming is low but not insignificant,
      and problematic gaming may be contained within a larger spectrum of externalizing
      behaviors. More research is needed to define safe levels of gaming, refine the
      definition of problematic gaming, and evaluate effective prevention and
      intervention strategies.

PMID- 21078730
TI  - Impact of income and income inequality on infant health outcomes in the United
      States.
AB  - OBJECTIVES: The goal was to investigate the relationships of income and income
      inequality with neonatal and infant health outcomes in the United States.
      METHODS: The 2000-2004 state data were extracted from the Kids Count Data Center.
      Health indicators included proportion of preterm births (PTBs), proportion of
      infants with low birth weight (LBW), proportion of infants with very low birth
      weight (VLBW), and infant mortality rate (IMR). Income was evaluated on the basis
      of median family income and proportion of federal poverty levels; income
      inequality was measured by using the Gini coefficient. Pearson correlations
      evaluated associations between the proportion of children living in poverty and
      the health indicators. Linear regression evaluated predictive relationships
      between median household income, proportion of children living in poverty, and
      income inequality for the 4 health indicators. RESULTS: Median family income was
      negatively correlated with all birth outcomes (PTB, r = -0.481; LBW, r = -0.295;
      VLBW, r = -0.133; IMR, r = -0.432), and the Gini coefficient was positively
      correlated (PTB, r = 0.339; LBW, r = 0.398; VLBW, r = 0.460; IMR, r = 0.114). The
      Gini coefficient explained a significant proportion of the variance in rate for
      each outcome in linear regression models with median family income. Among
      children living in poverty, the role of income decreased as the degree of poverty
      decreased, whereas the role of income inequality increased. CONCLUSIONS: Both
      income and income inequality affect infant health outcomes in the United States.
      The health of the poorest infants was affected more by absolute wealth than
      relative wealth.

PMID- 21078731
TI  - Genetically confirmed CADASIL in a pediatric patient.
AB  - A 17-year-old girl presented with migraine with prolonged aura and aura without
      headache. Neurologic examination was normal. Her mother, who did not have a
      history of migraine, developed right-face and -arm numbness at the age of 45.
      Evaluation revealed white matter changes consistent with CADASIL (cerebral
      autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy), and genetic testing showed a Notch3 gene mutation
      consistent with CADASIL. Our patient's MRI revealed white matter changes and the
      same Notch3 gene mutation. Low-dose aspirin was started in an attempt to prevent
      stroke. CADASIL is considered a degenerative disease of adult onset that leads to
      progressive neurologic deterioration. Onset of symptoms is in the third decade.
      Migraine, one of its most common manifestations, can develop in childhood.
      Evaluation for secondary causes is warranted in select pediatric patients who
      present with atypical migraine, when there is a family history of CADASIL or
      atypical patterns such as aura without headache, or in the presence of white
      matter abnormalities. The pathophysiology of CADASIL is poorly understood, and
      there is no proven effective therapy. Patients require genetic counseling and
      close follow-up. It is not known if interventions such as antiplatelet therapy
      are beneficial if instituted early in the course of the disease. Screening of
      family members at risk for CADASIL, even in the pediatric population, should be
      considered and offered to patients with CADASIL and their families. CADASIL has
      rarely been described in the pediatric population. This case report expands our
      current understanding of the disorder in children.

PMID- 21078732
TI  - Effects of current size, postnatal growth, and birth size on blood pressure in
      early childhood.
AB  - OBJECTIVE: In a prospective study, we investigated the impact of early growth on
      blood pressure at 3 years of age. METHODS: We measured systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) for 590 children 3 years of age and
      related measurements to current size and size at birth, 6 months, 1 year, and 2
      years of age. RESULTS: SBP was related positively to weight at 3 and 2 years and,
      after adjustment for current size, negatively to weight at birth and 6 months but
      not at 1 or 2 years. No effect was observed for DBP. A family history of
      hypertension was associated with higher maternal blood pressure, greater weight,
      and gestational hypertension (P = .05). Mothers with a history of gestational
      hypertension had higher SBP and DBP values (P < .001). In multivariate linear
      regression analyses, SBP was influenced positively by weight at 3 years and
      family history of hypertension and negatively by weight at 6 months. None of the
      factors was associated with DBP. CONCLUSIONS: For 3-year-old children, current
      weight was a determinant of SBP and postnatal growth to 6 months of age was more
      predictive than birth weight. A family history of hypertension is important in
      determining maternal blood pressure. These observations suggest a window in which
      postnatal growth might be modified.

PMID- 21078734
TI  - Aerosol inhalation from spacers and valved holding chambers requires few tidal
      breaths for children.
AB  - OBJECTIVE: The goal was to determine the number of breaths required to inhale
      salbutamol from different spacers/valved holding chambers (VHCs). METHODS:
      Breathing patterns were recorded for 2- to 7-year-old children inhaling placebo
      from 4 different spacers/VHCs and were simulated by a flow generator. Drug
      delivery with different numbers of tidal breaths and with a single maximal breath
      was compared. RESULTS: With tidal breathing, mean inhalation volumes were large,
      ranging from 384 mL to 445 mL. Mean values for drug delivery with an Aerochamber
      Plus (Trudell, London, Canada) were 40% (95% confidence interval [CI]: 34%-46%)
      and 41% (95% CI: 36%-47%) of the total dose with 2 and 9 tidal breaths,
      respectively. Mean drug delivery values with these breath numbers with a Funhaler
      (Visiomed, Perth, Australia) were 39% (95% CI: 34%-43%) and 38% (95% CI: 35%
      42%), respectively. With a Volumatic (GlaxoSmithKline, Melbourne, Australia),
      mean drug delivery values with 2 and 9 tidal breaths were 37% (95% CI: 33%-41%)
      and 43% (95% CI: 40%-46%), respectively (P = .02); there was no significant
      difference in drug delivery with 3 versus 9 tidal breaths. With the modified soft
      drink bottle, drug delivery. Drug delivery was not improved with a single maximal
      breath with any device. CONCLUSION: For young children, tidal breaths through a
      spacer/VHC were much larger than expected. Two tidal breaths were adequate for
      small-volume VHCs and a 500-mL modified soft drink bottle, and 3 tidal breaths
      were adequate for the larger Volumatic VHC.

PMID- 21078735
TI  - A randomized controlled trial of Lactobacillus GG in children with functional
      abdominal pain.
AB  - OBJECTIVE: Our aim was to determine whether Lactobacillus rhamnosus GG (LGG)
      relieves symptoms in children with recurrent abdominal pain. PATIENTS AND
      METHODS: A total of 141 children with irritable bowel syndrome (IBS) or
      functional pain were enrolled in 9 primary care sites and a referral center.
      Children entered a randomized, double-blind, placebo-controlled trial and
      received LGG or placebo for 8 weeks and entered follow-up for 8 weeks. The
      primary outcome was overall pain at the end of the intervention period. At entry
      and at the end of the trial, children underwent a double-sugar intestinal
      permeability test. RESULTS: Compared with baseline, LGG, but not placebo, caused
      a significant reduction of both frequency (P < .01) and severity (P < .01) of
      abdominal pain. These differences still were significant at the end of follow-up
      (P < .02 and P < .001, respectively). At week 12, treatment success was achieved
      in 48 children in the LGG group compared with 37 children in the placebo group (P
      < .03); this difference still was present at the end of follow-up (P < .03). At
      entry, 59% of the children had abnormal results from the intestinal permeability
      test; LGG, but not placebo, determined a significant decrease in the number of
      patients with abnormal results from the intestinal permeability testing (P <
      .03). These effects mainly were in children with IBS. CONCLUSIONS: LGG
      significantly reduces the frequency and severity of abdominal pain in children
      with IBS; this effect is sustained and may be secondary to improvement of the gut
      barrier.

PMID- 21078736
TI  - Educational outreach to reduce immunization pain in office settings.
AB  - OBJECTIVE: The goal was to examine the impact of a teaching module on
      immunization pain reduction practices in pediatric offices 1 and 6 months after
      the intervention. METHODS: Fourteen practices were selected randomly to receive a
      1-hour teaching session on immunization pain reduction techniques, and 13
      completed the study. Before the intervention, telephone interviews were conducted
      with parents concerning their children's recent immunization experiences. At 1
      and 6 months after the intervention, parents of children who had recent
      immunizations were interviewed by using the same questionnaires. Clinicians also
      were surveyed at baseline and at 6 months. RESULTS: A total of 839 telephone
      interviews and 92 clinician surveys were included. Significant changes from
      baseline were identified at 1 and 6 months after the intervention. At 1 month,
      parents were more likely to report receiving information (P = .04), using
      strategies to reduce pain (P < .01), learning something new (P < .01), using a
      ShotBlocker (P < .01), using sucrose (P < .01), and having higher levels of
      satisfaction (P = .015). At 6 months, all rates remained significantly higher
      than baseline findings (all P < .01) except for satisfaction. Clinician surveys
      revealed significant increases in the use of longer needles, sucrose, pinwheels,
      focused breathing, and ShotBlockers at 6 months. CONCLUSIONS: A 1-hour teaching
      session had measurable effects on the use of pain-reducing strategies at 1 and 6
      months after the intervention. This research supports the hypothesis that small
      group teaching sessions at the site of care can be associated with changes in
      practice behaviors.

PMID- 21078737
TI  - Youth motorcycle-related hospitalizations and traumatic brain injuries in the
      United States in 2006.
AB  - OBJECTIVES: The objectives were to provide national injury and health care cost
      estimates for youth motorcycle injuries in traffic and nontraffic settings and to
      focus on the burden of serious motorcycle-related traumatic brain injuries (TBIs)
      in children and young adults. METHODS: The 2006 Kids' Inpatient Database is a
      sample of inpatient discharges for US patients <21 years of age from 38 states.
      This cross-sectional analysis of the 2006 Kids' Inpatient Database included
      comparisons of TBI versus non-TBI and traffic versus nontraffic motorcycle
      related crashes for ages 12 to 20, with national estimates of hospital charges
      and costs, length of stay, severity, and long-term disability rates. RESULTS:
      Motorcycle-related crashes accounted for 5662 discharges (95% confidence
      interval: 5201-6122 discharges), which amounts to 3% of injury hospitalizations
      among youths and 5% of TBI diagnoses; two-thirds of cases were traffic-related,
      and one-third of patients sustained a TBI (1793 patients [95% confidence
      interval: 1631-1955 patients]). Among patients with TBIs, the overall probability
      of long-term disability was 24%. Patients with TBIs were 3.6 times more likely to
      be discharged to a rehabilitation facility and >10 times more likely to die in
      the hospital than were patients without TBIs. CONCLUSIONS: Motorcycle injuries
      are a substantial cause of youth injury hospitalizations. The large proportion,
      costs, and morbidity of TBI diagnoses in youth motorcycle crashes emphasize the
      need for effective crash prevention and head protection.

PMID- 21078738
TI  - Iatrogenic events in neonates: beneficial effects of prevention strategies and
      continuous monitoring.
AB  - OBJECTIVES: To assess the impact of continuous incident reporting and subsequent
      prevention strategies on the incidence of severe iatrogenic events and targeted
      priorities in admitted neonates. METHODS: We performed preintervention (January 1
      to September 1, 2005) and postintervention (January 1, 2008, to January 1, 2009)
      prospective investigations based on continuous incident reporting. Patient-safety
      initiatives were implemented for a period of 2 years. The main outcome was a
      reduction in the incidence of severe iatrogenic events. Secondary outcomes were
      improvements in 5 targeted priorities: catheter-related infections; invasive
      procedures; unplanned extubations; 10-fold drug infusion-rate errors; and severe
      cutaneous injuries. RESULTS: The first and second study periods included totals
      of 388 and 645 patients (median gestational ages: 34 and 35 weeks, respectively;
      P = .015). In the second period the incidence of severe iatrogenic events was
      significantly reduced from 7.6 to 4.8 per 1000 patient-days (P = .005).
      Infections related to central catheters decreased significantly from 13.9 to 8.2
      per 1000 catheter-days (P < .0001), as did exposure to central catheters, which
      decreased from 359 to 239 days per 1000 patient-days (P < .0001). Tenfold drug
      dosing errors were reduced significantly (P = .022). However, the number of
      unplanned extubations increased significantly from 5.6 to 15.5 per 1000
      ventilation-days (P = .03). CONCLUSIONS: Prospective, continuous incident
      reporting followed by the implementation of prevention strategies are
      complementary procedures that constitute an effective system to improve the
      quality of care and patient safety.

PMID- 21078733
TI  - Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia.
AB  - OBJECTIVE: The goal was to describe the temporal pattern of neonatal plasma
      glucose levels and associations with maternal glucose levels, cord serum C
      peptide levels, and neonatal size and adiposity. METHODS: A total of 17,094
      mothers and infants were included in the Hyperglycemia and Adverse Pregnancy
      Outcome Study (15 centers in 9 countries). Mothers underwent a 75-g, 2-hour, oral
      glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Cord blood and
      neonatal blood samples were collected. Biochemical neonatal hypoglycemia was
      defined as glucose levels of <10th percentile (2.2 mmol/L). Clinically identified
      hypoglycemia was ascertained through medical record review and associations were
      assessed. RESULTS: Plasma glucose concentrations were stable during the first 5
      hours after birth. Maternal glucose levels were weakly positively associated with
      biochemical neonatal hypoglycemia (odds ratios: 1.07-1.14 for 1-SD higher OGTT
      glucose levels). Frequency of neonatal hypoglycemia was higher with higher cord C
      peptide levels (odds ratio: 11.6 for highest versus lowest C-peptide category).
      Larger and/or fatter infants were more likely to have hypoglycemia (P < .001),
      and infants with hypoglycemia tended to have a higher frequency of cord C-peptide
      levels of >90th percentile. CONCLUSIONS: Mean neonatal plasma glucose
      concentrations varied little in the first 5 hours after birth, which suggests
      normal postnatal adjustment. Biochemical and clinical hypoglycemia were weakly
      related to maternal OGTT glucose measurements but were strongly associated with
      elevated cord serum C-peptide levels. Larger and/or fatter infants were more
      likely to develop hypoglycemia and hyperinsulinemia. These relationships suggest
      physiologic relationships between maternal glycemia and fetal insulin production.

PMID- 21078739
TI  - Starved for attention.

PMID- 21078740
TI  - Emergency reversal of warfarin anticoagulation.

PMID- 21078742
TI  - Use of recombinant factor VIIa for the prevention and treatment of bleeding in
      patients without hemophilia: a systematic review and meta-analysis.
AB  - BACKGROUND: The benefits and risks of off-label use of recombinant factor VIIa in
      patients without hemophilia are contested. We performed a systematic review to
      assess the effectiveness and safety of such use. METHODS: We searched electronic
      databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials
      comparing recombinant factor VIIa with placebo in any patient population except
      those with hemophilia up to January 2010. Eligible articles were assessed for
      inclusion, data were extracted, and study quality was evaluated. Outcomes
      included mortality, blood loss, requirements for red blood cell transfusion,
      number of patients transfused and thromboembolic events. RESULTS: We identified
      26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137)
      and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic
      use, we found no significant difference in mortality or thromboembolic events
      between the treatment and placebo groups. We found modest benefits favouring
      recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95%
      confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted
      mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients
      transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials,
      we found a nonsignificant decrease in mortality and a nonsignificant increase in
      thromboembolic events but no difference in control of bleeding or red blood cell
      transfusion. INTERPRETATION: Clinically significant benefits of recombinant
      factor VIIa as a general hemostatic agent in patients without hemophilia remain
      unproven. Given its potential risks, such use cannot be recommended, and in most
      cases, it should be restricted to clinical trials.

PMID- 21078744
TI  - Personal fertility monitors for contraception.

PMID- 21078743
TI  - Subcutaneous seroma after diagnostic thoracentesis.

PMID- 21078745
TI  - Legal challenges may imperil medicare, public health care advocates say.

PMID- 21078746
TI  - Republicans take aim at "Obamacare".

PMID- 21078747
TI  - Pan-Canadian strategy being developed to tackle mental health in prisons.

PMID- 21078748
TI  - Unregulated hyperbaric oxygen therapy clinics assailed.

PMID- 21078749
TI  - Europe develops action plan to address health workforce shortfall.

PMID- 21078750
TI  - Prevention and control of chronic diseases.

PMID- 21078751
TI  - Organ donation.

PMID- 21078752
TI  - New drugs for hyponatraemia.

PMID- 21078753
TI  - Fighting big tobacco in Spain.

PMID- 21078754
TI  - Gruesome by design.

PMID- 21078756
TI  - Community care networks could help 200,000 more people die at home instead of
      hospital.

PMID- 21078757
TI  - Gout.

PMID- 21078759
TI  - Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus
      erythematosus.
AB  - To investigate the associations of DNA methylation levels and mRNA expressions of
      DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2)
      with systemic lupus erythematosus (SLE), 108 patients with SLE and 97 healthy
      controls were enrolled in this study. DNA and total RNA were extracted from the
      peripheral blood mononuclear cells of the SLE patients and the controls. The
      global methylation levels of DNA were measured in 63 patients with SLE and 68
      healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in
      108 SLE patients and 97 controls using the quantitative real-time polymerase
      chain reaction method. The global methylation level of DNA was significantly
      decreased in the SLE patients in comparison with that in the controls (p < 0.001,
      95% CI = 0.1573-0.5052). The patients with SLE have higher expressions of DNMT1
      and MBD2 mRNA than the controls (p < 0.001, 95% CI = -0.0049 - -0.0019 and p =
      0.001, 95% CI = -0.0119 - -0.0029, respectively). We also found that there were
      no significant differences in the methylation level and the expression of DNMT1
      and MBD2 mRNA between the active and the inactive SLE patients. A positive
      correlation was also found between DNMT1 and MBD2 mRNA expressions in the SLE
      patients (p < 0.001). This study demonstrated that the patients with SLE had a
      significantly lower level of DNA methylation than the controls. The expression of
      both DNMT1 and MBD2 mRNA was significantly increased in the SLE patients compared
      with the controls. This study also showed a positive correlation between DNMT1
      and MBD2 mRNA levels in the patients with SLE.

PMID- 21078760
TI  - Differential expression of factors involved in the intrinsic and extrinsic
      apoptotic pathways in juvenile systemic lupus erythematosus.
AB  - Dysregulated neutrophil apoptosis may result in the development of autoimmune
      disease by contributing to nuclear autoantigen exposure, leading to autoantibody
      generation and a breakdown in immune tolerance. It has previously been shown that
      neutrophil apoptosis is increased in juvenile-onset systemic lupus erythematosus
      (JSLE). This study aims to investigate the pathways involved in JSLE serum
      induced apoptosis. Caspases 3, 7-9, IAP1/2, XIAP and FADD mRNA levels and TRAIL
      R2, BID/tBID, caspase 8 and 9 protein expression were measured in neutrophils
      from JSLE patients (n = 14) and controls (n = 10). The mRNA levels of caspases 7
      9 were significantly higher in JSLE neutrophils than in controls, whereas the
      mRNA levels of IAP1, IAP2 and XIAP were decreased (p < 0.05). A decrease in
      neutrophil apoptosis induced by JSLE serum was observed in the presence of
      caspase 8 and 9 inhibitors (p < 0.05), and the activity of caspases 8 and 9
      increased over time. tBID protein expression increased following incubation with
      JSLE serum. These data focus specifically on the expression and activity of the
      main caspases in the intrinsic and extrinsic apoptotic pathways. Increased
      expression of factors involved in the downstream signalling of the extrinsic
      apoptotic pathway indicates a prominent involvement of this pathway in JSLE serum
      induced apoptosis.

PMID- 21078762
TI  - Association of single-nucleotide polymorphisms in FOXP3 gene with systemic lupus
      erythematosus susceptibility: a case-control study.
AB  - Foxp3, encoded by the human FOXP3 gene, is a transcription factor that regulates
      regulatory T-cell (Treg) development and function. Associations have been
      reported between FOXP3 gene variants and autoimmune endocrinopathy and non
      endocrine autoimmune disease. The aim of this study was to investigate the
      possible influence of single nucleotide polymorphisms (SNP) in the FOXP3 gene on
      genetic predisposition to systemic lupus erythematosus (SLE). The study cohort
      comprised 172 SLE patients and 181 controls, who were genotyped for the FOXP3
      gene variants. Of five SNPs identified, the FOXP3 -6054 ATT carrier was shown to
      be associated with renal disorder (odds ratio [OR] 3.26, 95% confidence interval
      [95% CI] 1.33-8.03, p = 0.0077). Furthermore, lower anti-dsDNA levels were found
      in patients with the -3279 A carrier (p = 0.0109). To the authors' knowledge,
      this is the first study to investigate the association of FOXP3 SNPs with
      susceptibility to SLE, as well as sub-phenotype susceptibility. Although the
      exact role of Foxp3 and FOXP3 gene variations in SLE is still not clear, the
      present data support the importance of variations in the FOXP3 gene region for
      the etiology of certain manifestations of SLE.

PMID- 21078761
TI  - Elevation of serum CXCL13 in SLE as well as in sepsis.
AB  - Recent studies have demonstrated that CXCL13 serum levels correlate significantly
      with systemic lupus erythematosus (SLE) disease activity. However, experimental
      studies show that CXCL13 production can also be induced by bacterial exposure as
      well as in response to inflammatory cytokines. This report asks whether CXCL13
      serum levels are elevated in patients with evidence of bacterial infections and
      whether there is a correlation with the C-reactive protein (CRP) levels or the
      severity of illness in critically ill patients. CXCL13 levels were compared in 39
      patients with active SLE (without concomitant infection), 40 non-SLE patients
      with sepsis, and 40 healthy controls by enzyme-linked immunosorbent assay (ELISA)
      methodology. We also tested storage conditions and freeze-thaw cycles for
      stability of CXCL13 in serum samples. Our studies demonstrated that the median
      CXCL13 serum levels were significantly elevated in patients with SLE [median 83
      pg/ml (interquartile range 38-366)] or sepsis [359 pg/ml (151-459)] compared with
      healthy controls [32 pg/ml (27-41), p < 0.001]. The CXCL13 serum levels
      correlated with disease activity in SLE (CXCL13 vs. SLEDAI r = 0.65, p < 0.001),
      but were not associated with severity of illness score in critically ill patients
      (CXCL13 vs. SOFA r = -0.15, p = 0.35). However, CXCL13 serum levels were clearly
      associated with CRP levels in both sepsis (r = 0.45, p = 0.003) and SLE (r =
      0.39, p = 0.02). In conclusion, CXCL13 is a stable serum marker for disease
      activity in SLE patients, but concomitant infections can also lead to increased
      CXCL13 levels.

PMID- 21078763
TI  - Relationship between cardiac symptoms, myocardial perfusion defects and coronary
      angiography findings in systemic lupus erythematosus.
AB  - Coronary angiography is generally regarded as the 'gold standard' test for
      diagnosing coronary artery disease (CAD). We sought to determine the relationship
      between cardiac symptoms and findings of coronary angiography and myocardial
      perfusion scintigraphy (MPS) in patients with systemic lupus erythematosus (SLE).
      Medical records of all SLE patients who underwent coronary angiography while
      attending our clinic over 24 years were reviewed, noting the indication for the
      test and its findings. Among patients who had MPS within 6 months prior to
      coronary angiography, a contingency table was used to rate the agreement between
      the two tests. Among the 35 patients who underwent coronary angiography, 31 had
      the test to investigate cardiac symptoms. Among the symptomatic patients, 17
      (55%) had an abnormal angiogram with one or more plaques, while 14 (45%) had
      normal angiograms. All four asymptomatic patients had normal angiograms. Compared
      to those with normal angiograms, patients with abnormal angiograms had a higher
      mean number of cardiovascular risk factors per patient (1.6 +/- 1.4 vs. 0.6 +/-
      1.0, p = 0.02). Twenty-four patients had both angiography and MPS. Overall, the
      agreement between angiography and MPS was poor (kappa = 0, p = 0.0008), with 14
      (58.3%) patients having perfusion defects and normal angiograms. A proportion of
      SLE patients with cardiac symptoms do not have plaques on coronary angiography.
      Overall there is poor agreement between the findings of coronary angiography and
      MPS in SLE, suggesting mechanisms of ischemia other than plaques.

PMID- 21078764
TI  - Common mental disorders and psychological distress in systemic lupus
      erythematosus are not associated with disease activity.
AB  - Psychiatric diagnosis in patients with systemic lupus erythematosus (SLE) is
      controversial: variations have been reported in frequency, diagnostic assays,
      associations with disease activity, autoantibodies, and contributing social
      factors. Eighty-three consecutive non-selected Chilean patients with SLE were
      evaluated for: (i) 26 common mental disorders according to the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the Mini
      International Neuropsychiatric Interview (MINI-plus); (ii) psychological
      suffering measured by Hospital Anxiety and Depression Scale (HADS); (iii) ACR
      1999 neuropsychiatric (NP)SLE criteria; (iv) SLE disease activity (SLEDAI-2K);
      (v) cumulative damage (SLICC/ACR); and (vi) anti-ribosomal P antibodies by enzyme
      linked immunoassay and immunoblot. Psychiatric diagnoses occurred in 44.6% of
      patients; the most frequent (21.7%) was major depressive episode (MDE). No
      association with lupus activity was observed in patients with a DSM-IV diagnosis
      or MDE or psychological suffering. ACR 1999 NPSLE criteria were present in 42.2%
      of patients, the majority corresponding to mood (28.9%) or anxiety disorders
      (15.6%). Suicidal risk was present in 9.6% of patients. Anti-ribosomal P
      antibodies (13.3%) were not associated with DSM-IV diagnosis. Severe psychiatric
      disorders in SLE are common and not associated with disease activity.

PMID- 21078765
TI  - Collapsing glomerulopathy associated with proliferative lupus nephritis:
      reversible acute kidney injury.
AB  - Collapsing glomerulopathy is a rare form of glomerular injury, characterized by
      segmental or global collapse of the glomerular capillaries, wrinkling and
      retraction of the glomerular basement membrane, and marked hypertrophy and
      hyperplasia of podocytes. Prognosis is usually poor, with most cases developing
      end-stage renal disease, in spite of treatment. The association of collapsing
      glomerulopathy and systemic lupus erythematosus is very unusual. In this report,
      we describe the first case of a simultaneous diagnosis of collapsing
      glomerulopathy and diffuse proliferative lupus nephritis. The case presented with
      acute kidney injury and nephrotic syndrome and evolved with partial remission of
      nephrotic syndrome and recovery of renal function after aggressive treatment with
      intravenous cyclophosphamide and methylprednisolone.

PMID- 21078766
TI  - The association between the PTPN22 C1858T polymorphism and systemic lupus
      erythematosus: a meta-analysis update.
AB  - The aim of this study was to determine whether the functional protein tyrosine
      phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers
      susceptibility to systemic lupus erythematosus (SLE) in ethnically different
      populations. A meta-analysis was conducted on the PTPN22 C1858T polymorphism
      across 11 comparative studies. Meta-analysis showed an association between the
      PTPN22 1858T allele and SLE in all study subjects (odds ratio (OR) 1.560, 95%
      confidence interval (CI) 1.336, 1.822, p = 2.0 * 10(-8)). Analysis after
      stratification by ethnicity indicated that the PTPN22 1858T allele was
      significantly associated with SLE in Europeans and Hispanics (OR 1.490, 95% CI
      1.280, 1.735, p = 2.0 *10(-8); OR 2.355, 95% CI 1.644, 3.373, p = 2.9 * 10(-6)).
      The meta-analysis showed that the C/T + T/T genotype was associated with
      susceptibility to SLE in all study subjects, Europeans, and Hispanics
      populations, and an association between the T/T genotype with SLE in Europeans.
      African Americans had a much lower prevalence of the T allele (2.2%) than any
      other population studied, and Europeans had the highest frequency (9.5%). In
      conclusion, this meta-analysis confirms that the PTPN22 C1858T polymorphism is
      associated with SLE susceptibility in different ethnic groups, and that its
      prevalence is ethnicity dependent.

PMID- 21078767
TI  - Subclavian artery stenosis: a review for the vascular medicine practitioner.
AB  - Peripheral artery disease assessment typically focuses on the evaluation of lower
      extremity symptoms and physical findings. Few practitioners consider the
      importance of upper extremity arterial disease; which, besides causing hand and
      arm symptoms, can be associated with significant neurologic and cardiac sequelae.
      A review of the existing literature through PubMed using the search term
      'subclavian stenosis' was performed. The latest original articles, including
      clinical studies, case reports and limited reviews of this topic were adapted. A
      comprehensive article review focusing on the diagnostic and treatment approach
      for subclavian stenosis was prepared. In conclusion, vascular medicine
      practitioners including cardiologists and vascular surgeons caring for patients
      with arterial disease should routinely assess for subclavian stenosis. There are
      excellent screening tools and effective medical therapies which can be instituted
      if diagnosed early. When the need for revascularization arises, percutaneous
      modalities are favored given their proven long-term efficacy, decreased morbidity
      and mortality, and cost-effectiveness.

PMID- 21078768
TI  - Effects of peri-operative glucose levels on adverse outcomes in infants receiving
      open-heart surgery for congenital heart disease with cardiopulmonary bypass.
AB  - OBJECTIVE: Studies designed to evaluate the association of hyperglycemia and
      adverse events in pediatric patients receiving open cardiac surgery have yielded
      inconsistent results. The aim of this retrospective, observational study was to
      evaluate the effects of peri-operative glucose levels on adverse events in
      infants receiving open-heart surgery with CPB. METHODS: From Nov 2009 through Dec
      2009, 100 infants undergoing open-heart surgery were enrolled. All glucose values
      during the operation and intensive care unit stay were documented. Metrics of
      glucose control, including mean, peak and minimum glucose levels were calculated.
      Hyperglycemia was defined as a mean glucose above 150 mg/dl. Hypoglycemia was
      defined as minimum glucose below 65 mg/dl. Multivariable regression analyses were
      used to determine relationships between these metrics of glucose control and a
      composite morbidity-mortality outcome after controlling for multiple variables
      known to influence early outcomes after congenital heart surgery. RESULTS:
      According to our definition, 43 patients (43%) developed hyperglycemia and 9
      patients (9%) developed at least one episode of hypoglycemia. A total of 58
      patients reached the overall composite morbidity-mortality end point at some
      point during the study period. After adjusting the effects of age, cross-clamp
      time and pre-operative percutaneous oxygen saturation by multivariable analysis,
      euglycemia, defined as mean glucose <=150 mg/dl, was found to be a significant
      predictor for morbidity, with an odds ratio of 5.1(95% confidence interval 1.5
      17.5). CONCLUSION: In contrast to adult critically ill patients, data from the
      present study did not prove that hyperglycemia was detrimental to infants
      receiving open-heart surgery with CPB. The existing literature and findings of
      our present study warranted future clinical studies of strict glycemic control in
      critically ill children, considering a more permissive glycemic range as a
      desirable target.

PMID- 21078769
TI  - Correlation between cerebral tissue and central venous oxygen saturation during
      off-pump coronary bypass graft surgery.
AB  - We compared simultaneous regional cerebral oxygen saturation and central venous
      oxygen saturation at different time periods in 20 adult patients (median age,
      57.9; range, 35 to 76 years) undergoing off-pump coronary artery bypass (OPCAB)
      graft surgery (n= 20). Mean arterial pressure (MAP), partial pressure of carbon
      dioxide (PcvCO(2)), heart rate, haematocrit (Hct), lactate and patient oxygen
      saturation (SpO(2)) were also recorded as a secondary analysis to determine
      independent predictors of cerebral desaturation and interactions between
      predictors. The cross-sectional analysis performed at each time point showed
      several significant moderate to strong positive correlations between central
      venous oxygen saturation and both right and left cerebral oxygen saturations;
      however, right cerebral saturations correlated better with central venous
      saturations than left cerebral saturation. Partial pressure of carbon dioxide
      (PcvCO(2)) was identified as a major predictor of cerebral saturation 0.59 (p <
      0.001). Central venous saturation can be used as a surrogate measure of cerebral
      oxygen saturation during OPCAB surgery.

PMID- 21078770
TI  - Expression of urokinase plasminogen activator receptor on monocytes and
      granulocytes is modulated by cardiac surgery.
AB  - AIMS: Coronary artery bypass grafting (CABG) is linked to the induction of the
      blood coagulation/fibrinolysis cascade, which is an integral component of
      inflammation induced by cardiac surgery. We followed the modulation of urokinase
      plasminogen activator receptor uPAR (CD87) separately for monocytes and
      granulocytes in blood of cardiac surgery patients. METHODS: Expression of uPAR,
      analyzed as Median Fluorescence Intensity (MFI), on blood monocytes and
      granulocytes was determined by flow cytometry. Changes in uPAR expression in
      patients undergoing CABG using standard cardiopulmonary bypass ("on-pump") were
      compared to the changes in uPAR expression in patients undergoing CABG using mini
      invasive cardiopulmonary bypass ("mini on-pump"). RESULTS: In "on-pump" patients,
      the median of uPAR expression on granulocytes before surgery was 18.1
      (InterQuartile Range (IQR): 15.6-20.4). uPAR expression was significantly
      decreased after surgery (p<0.001), on the first postoperative day (p<0.001), and
      on the third postoperative day (p<0.05). In "mini on-pump" patients, the median
      of uPAR expression on granulocytes before surgery was 15.2 (IRQ: 13.8-19.4). The
      significantly decreased uPAR expression was found only at the end of surgery
      (p<0.05). The similar pattern of uPAR expression was also found for monocytes.
      The preoperative level in "on-pump" patients was 23.3 (IRQ: 18.9-30.2). There was
      significantly decreased uPAR expression at the end of surgery (p<0.01) and at the
      first postoperative day (p<0.05). In "mini on-pump" patients, the preoperative
      uPAR expression was 16.9 (IQR: 14.5-20.2). Expression of uPAR was significantly
      decreased only after surgery (p<0.05). When comparing "onpump" patients to "mini
      on-pump" patients, no significant differences in the expression of uPAR were
      found. CONCLUSION: uPAR expression on granulocytes and monocytes is significantly
      modulated by cardiac surgery.

PMID- 21078771
TI  - Myocardial perfusion imaging using a technetium-99m sestamibi in asymptomatic and
      low risk for coronary artery disease patients with diagnosed systemic lupus
      erythematosus.
AB  - INTRODUCTION: The aim of the present study was to evaluate technetium-99m
      sestamibi single photon emission tomography (SPECT) myocardial perfusion imaging
      (MPI) and its association with some clinical and laboratory parameters in an
      asymptomatic systemic lupus erythematosus (SLE) population. MATERIALS AND
      METHODS: Twenty-one subjects with SLE and no suspected or documented coronary
      artery disease (CAD) accomplished myocardial perfusion imaging. Some SLE and CAD
      parameters were also evaluated in association with myocardial SPECT. RESULTS:
      Twenty-one women with a diagnosis of SLE (mean age 36.9 +/- 12.8) entered the
      study. All patients were in the low-risk category for CAD pretest; however,
      abnormal myocardial perfusion results were found in eight (38%) patients. Amongst
      the traditional CAD risk factors, there was a significant association between the
      presence of dyslipidemia and myocardial perfusion abnormalities (P= 0.047).
      However, we found no significant association between other traditional and SLE
      specific risk factors. CONCLUSION: This study's significant finding was that
      asymptomatic CAD is common in SLE patients, even in those thought to be low risk
      for CAD and in the absence of cardiac symptoms.

PMID- 21078772
TI  - Inhibition effects of the classical pathway complement of isolated compounds from
      Quercus glauca.
AB  - Species of the Quercus species is an evergreen broadleaf tree found not only in
      Korea but also in China, Taiwan, and Japan. Quercus species is the most commonly
      occurring plant among the 50 native species of the family Fagaceae in Korea,
      China, and Taiwan. Quercus species have been used for diarrhea, dysentery,
      dermatitis, and hemorrhagia in Korean folk medicine. The present study evaluated
      the anticomplement effect of constituents from Quercus species (Fagaceae) in
      classical pathway complement system. We have evaluated leaves of five species of
      the Quercus genus with regard to its anticomplement activity and have identified
      its active principles following activity-guided isolation. Bioactivity-guided
      fractionation of the 80% methanol extracts of the stem barks of Quercus glauca
      Thunberg has led to the isolation of galloyl derivatives, displaying high
      anticomplement activity. Four galloyl derivatives isolated from the leaves of Q.
      glauca, namely 6'-O-galloyl salidroside (1), methyl gallate (2), 1,2,3,6
      tetragalloylglucose (3), and 1,2,6-trigalloylglucose (4). 1, 2, 3 and 4 showed
      inhibitory activity against complement system with 50% inhibitory concentrations
      (IC(50)) values of 224 MUM, 362.4 MUM, 32.3 MUM, and 138.3 MUM. Among the
      compounds tested, 3 showed the most potent anticomplement activity (IC(50), 32.3
      MUM). This is the first report of the isolation and anticomplement activity from
      Q. glauca.

PMID- 21078773
TI  - Antilipidemic activity of organic solvent extract from Sorghum bicolor on rats
      with diet-induced obesity.
AB  - The present study evaluated the antiobesity and lipid-lowering effects from
      dichloromethane and ethyl acetate extracts of Hwanggeumchal Sorghum varieties on
      Sorghum bicolor. The Hwanggeumchal Sorghum ethyl acetate extracts significantly
      reduced the plasma total cholesterol and triglyceride levels significantly when
      given orally at a dose of 50 and 300 mg/kg/day to the high-fat diet-induced obese
      rats for 2 weeks. These findings demonstrate the excellent pharmacological
      potential of Hwanggeumchal Sorghum varieties to prevent obesity.

PMID- 21078776
TI  - Procedure guideline for brain perfusion SPECT using 99mTc radiopharmaceuticals
      3.0.

PMID- 21078775
TI  - Unsaturated FAs prevent palmitate-induced LOX-1 induction via inhibition of ER
      stress in macrophages.
AB  - Palmitic acid (PA) upregulates oxidized LDL receptor-1 (LOX-1), a scavenger
      receptor responsible for uptake of oxidized LDL (oxLDL), and enhances oxLDL
      uptake in macrophages. However, the precise underlying mechanism remains to be
      elucidated. PA is known to induce endoplasmic reticulum (ER) stress in various
      cell types. Therefore, we investigated whether ER stress is involved in PA
      induced LOX-1 upregulation. PA induced ER stress, as determined by
      phosphorylation of PERK, eIF2alpha, and JNK, as well as induction of CHOP in
      macrophage-like THP-1 cells. Inhibitors [4-phenylbutyric acid (PBA), sodium
      tauroursodeoxycholate (TUDCA), and salubrinal] and small interfering RNA (siRNA)
      for the ER stress response decreased PA-induced LOX-1 upregulation. Thapsigargin,
      an ER stress inducer, upregulated LOX-1, which was decreased by PBA and TUDCA. We
      next examined whether unsaturated FAs could counteract the effect of PA. Both
      oleic acid (OA) and linoleic acid (LA) suppressed PA-induced LOX-1. Activation of
      the ER stress response observed in the PA-treated cells was markedly attenuated
      when the cells were cotreated with OA or LA. In addition, OA and LA suppressed
      thapsigargin-induced LOX-1 upregulation with reduced activation of ER stress
      markers. Our results indicate that activation of ER stress is involved in PA
      induced LOX-1 upregulation in macrophages, and that OA and LA inhibit LOX-1
      induction through suppression of ER stress.

PMID- 21078774
TI  - Breaking through a plateau in renal cell carcinoma therapeutics: development and
      incorporation of biomarkers.
AB  - With the Food and Drug Administration approval of 6 novel targeted agents since
      December 2005 and limited comparative trials to discern relative efficacy, the
      treatment of metastatic renal cell carcinoma (RCC) has become immensely complex.
      The research community must look to novel ways in which to identify appropriate
      candidates for selected targeted therapies; one potential strategy is the use of
      clinical and molecular biomarkers. A growing body of knowledge-related von Hippel
      Lindau-driven pathways in this disease has highlighted the potential role of
      hypoxia-inducible factor subtypes in distinguishing RCC patients clinically.
      Techniques applied in other malignancies, such as gene expression and proteomic
      profiling, may also ultimately allow for clinical stratification. An emerging
      understanding of immunologic phenomena that may affect cancer progression (i.e.,
      tumor infiltration by CD68 lymphocytes, memory T-cells, etc.) has unveiled a
      number of other potential biomarkers of response. Several vascular endothelial
      growth factor receptor-directed therapies classically thought to function as
      antiangiogenics may also have complex effects upon the tumor microenvironment
      including the associated immune cell milieu. As such, immunologic parameters
      could potentially predict response to current therapies. Finally, clinical
      biomarkers, such as hypertension, may predict the efficacy of several currently
      available targeted agents, although implementation of such biomarkers remains
      challenging. Herein, the clinical relevance of putative RCC biomarkers is
      examined in detail.

PMID- 21078777
TI  - Detection of 90Y extravasation by bremsstrahlung imaging for patients undergoing
      90Y-ibritumomab tiuxetan therapy.
AB  - Extravasation of therapeutic (90)Y-ibritumomab tiuxetan can cause significant
      injury. Detection of extravasated (90)Y using a gamma-camera for patients
      undergoing (90)Y-ibritumomab tiuxetan therapy is a challenge because of the
      inherently low efficiency of bremsstrahlung imaging and the interference of
      prompt and scattered photons from (111)In that are still present in the body at
      the time of (90)Y injection. We have configured a gamma-camera to image
      bremsstrahlung radiation from superficial (90)Y in the presence of (111)In and
      evaluated the effectiveness using phantoms. METHODS: Phantoms were constructed to
      contain (90)Y and (111)In with activity levels and with a geometry approximating
      conditions in a patient being scanned for evaluation of possible extravasation in
      the antecubital fossa. Imaging was performed using a camera equipped with medium
      energy general-purpose (MEGP) and high-energy general-purpose (HEGP) collimators.
      RESULTS: The contrast that developed between the patch representing extravasated
      solution and the background was comparable for MEGP and HEGP collimators. With
      MEGP collimators and 5-min acquisitions, a patch containing 8.3 MBq (220 MUCi)
      distributed over an elliptic area of 7 * 11 cm was clearly discernable.
      CONCLUSION: With our experimental arrangement, the lower limit of detection is
      approximately 8 MBq. We calculate that an extravasation of this much (90)Y would
      result in an absorbed dose to the skin and subcutaneous tissue of 2.5 Gy, which
      is close to the threshold for skin damage. This technique is therefore sensitive
      enough to be of use in the clinic when extravasation of (90)Y is suspected.

PMID- 21078778
TI  - Myocardial SPECT images for diagnosis of pulmonary hypertension and right
      ventricular hypertrophy.
AB  - The utility of (99m)Tc-tetrofosmin myocardial SPECT for assessment of pulmonary
      hypertension and right ventricular thickness has not been well studied. We
      hypothesized that a ratio of right ventricular activity to left ventricular
      activity (RV/LV uptake ratio) from SPECT myocardial perfusion images could
      identify the presence of increased right ventricular wall thickness and elevated
      systolic pulmonary artery pressure with or without the use of attenuation
      correction. METHODS: We identified 33 patients with normal findings on stress
      (99m)Tc-tetrofosmin left ventricular myocardial perfusion imaging who had a
      complete 2-dimensional echocardiographic study within 3 wk of the SPECT study.
      Two 6 * 6 pixel regions of interest were placed in the right and left ventricular
      free walls of both non-attenuation-corrected and attenuation-corrected SPECT
      images. We examined the correlation of RV/LV uptake ratio with echocardiographic
      right ventricular free-wall thickness and with pulmonary artery systolic
      pressure. RESULTS: RV/LV uptake ratio, measured on non-attenuation-corrected
      images, correlated significantly with both pulmonary artery systolic pressure (r
      = 0.63 and P < 0.001) and right ventricular wall thickness (r = 0.6 and P <
      0.001). Receiver-operating-characteristic analysis of the use of RV/LV uptake
      ratio to detect significant pulmonary hypertension showed that the area under the
      curve was 0.78 (95% confidence interval, 0.62-0.95). However, no significant
      correlation of RV/LV uptake ratio with pulmonary artery systolic pressure or
      right ventricular wall thickness was found on attenuation-corrected images.
      CONCLUSION: RV/LV uptake ratio measured on SPECT images can be used to identify
      patients with high pulmonary artery pressure or right ventricular hypertrophy.

PMID- 21078779
TI  - The 2011 nuclear medicine technology job analysis project of the American
      Registry of Radiologic Technologists.
AB  - The American Registry of Radiologic Technologists (ARRT) conducts periodic job
      analysis projects to update the content and eligibility requirements for all
      certification examinations. In 2009, the ARRT conducted a comprehensive job
      analysis project to update the content specifications and clinical competency
      requirements for the nuclear medicine technology examination. ARRT staff and a
      committee of volunteer nuclear medicine technologists designed a job analysis
      survey that was sent to a random sample of 1,000 entry-level staff nuclear
      medicine technologists. Through analysis of the survey data and judgments of the
      committee, the project resulted in changes to the nuclear medicine technology
      examination task list, content specifications, and clinical competency
      requirements. The primary changes inspired by the project were the introduction
      of CT content to the examination and the expansion of the content covering
      cardiac procedures.

PMID- 21078780
TI  - Effects of crystal pixel size and collimator geometry on the performance of a
      pixelated crystal gamma-camera using Monte Carlo simulation.
AB  - Dedicated gamma-cameras based on pixelated scintillators have long been used for
      breast tumor imaging. Intercrystal scattering (ICS) increases the background
      counting rate and degrades the image quality when small crystal pixels are used.
      Because of the small size of applied collimators, scattered radiation and septal
      penetration are high, and therefore collimator characteristics must be carefully
      considered. In our study, we investigated the influence of ICS events on position
      detection accuracy (PDA) for pixelated crystals and the effects of different
      geometries of hexagonal-hole collimators on the performance of these cameras,
      using Monte Carlo simulation to optimize camera design. The arrays of thallium
      doped cesium iodide detectors with different pixel dimensions that had been
      exposed to 140-keV photons of isotropic point source, 50 mm from the collimator
      surface, were simulated. Hexagonal-hole collimators were 10.5, 15, and 21 mm
      long. The septal thickness varied from 0.1 to 0.5 mm, with 3 different hole
      diameters. The results confirmed that by increasing the crystal pixel size, ICS
      was decreased and change of detection efficiency was negligible, but PDA,
      contrast-to-noise ratio, and spatial resolution (full width at half maximum) were
      increased. Our experiences confirmed that 2 * 2 mm was an optimum crystal pixel
      size, especially for a lower ICS fraction and an appropriate full width at half
      maximum. Because collimators are the limiting factor for spatial resolution and
      sensitivity, careful collimator design is of great importance.

PMID- 21078781
TI  - Optimization of low-dose CT protocol in pediatric nuclear medicine imaging.
AB  - This study was performed to find the optimal low-dose CT protocol for children
      being imaged on SPECT/CT scanners not equipped with automatic dose control. For
      SPECT/CT systems with manually adjustable x-ray tube voltage (kV) and anode
      current (mA), an optimized protocol makes it possible to minimize the dose to
      patients. METHODS: Using the 4-slice low-dose CT component of a commercially
      available SPECT/CT scanner, we compared the signals reaching the CT detector
      after radiation passes through objects of different sizes. First, the exit dose
      rates were measured for combinations of available voltages and currents. Next,
      imaging parameters were selected on the basis of acceptable levels of exit dose
      rates, cylindric phantoms of different diameters approximating children of
      different sizes were scanned using these parameters, and the quality of the CT
      images was evaluated. Finally, weighted CT dose indexes for abdomen and head CT
      dose phantoms simulating, respectively, adult and pediatric patients were
      measured using exactly the same techniques to estimate and compare doses to these
      2 groups of patients. RESULTS: For children with torsos smaller than 150 mm,
      imaging can be performed using the lowest available voltage and current (120 kV
      and 1 mA, respectively). For children with torsos less than 250 mm, 140 kV and
      1.5 mA can be used. For patients with torsos greater than 250 and less than 300
      mm, 140 kV and 2 mA can be used. Regarding the signal-to-noise ratio, all these
      parameters give an excellent signal and fully acceptable noise levels.
      CONCLUSION: For the SPECT/CT system studied, even the lowest available voltage
      and current used for scanning pediatric patients did not cause signal-to-noise
      degradation, and the use of these settings substantially lowered the dose to the
      patients.

PMID- 21078783
TI  - The gastric emptying study with oatmeal: reference range and reproducibility as a
      function of age and sex.
AB  - This study evaluated the reference range and reproducibility of the gastric
      emptying study with oatmeal as a function of age and sex. METHODS: Twenty-four
      healthy subjects, 12 men and 12 women, categorized into 3 age groups, 20-40, 40
      60, and 60-80 y, were studied twice, 1 d apart, with instant oatmeal labeled with
      (99m)Tc-sulfur colloid. Imaging was performed in the upright position using the
      left anterior oblique (LAO), right posterior oblique (RPO), anterior, and
      posterior projections. One-minute digital images acquired every 15 min for 60 min
      were used to calculate a simple half-time of emptying. RESULTS: A strong
      correlation was found among half-times of gastric emptying calculated from the
      anterior projection, LAO projection, anterior-posterior geometric mean, and LAO
      RPO geometric mean (P < 0.01). A significant inverse correlation was found
      between increasing age and decreasing half-time of emptying in men and women (P <
      0.05). A reference range of 10-60 min is suggested for 20- to 40-y-old patients,
      10-40 min for 40- to 60-y-olds, and 10-30 min for 60- to 80-y-olds. Half-times of
      emptying tended to be longer for women than for men (not statistically
      significant). There was a large variation between the first and second studies,
      with a trend toward decreasing variation with increasing age in both men and
      women. In repeated studies, a reference range of variation of up to 30 min is
      suggested for 20- to 40-y-old patients, up to 20 min for 40- to 60-y-olds, and up
      to 15 min for 60- to 80-y-olds. CONCLUSION: The reference range for half-time of
      gastric emptying with instant oatmeal decreases with increasing age in both men
      and women. Test-retest variation is relatively large and tends to decrease with
      increasing age in both men and women. Data from either the LAO projection or the
      anterior-posterior geometric mean are acceptable for calculating the half-time of
      gastric emptying.

PMID- 21078784
TI  - The effectiveness of decontamination products in the nuclear medicine department.
AB  - This study assesses the effectiveness of using everyday cleaning agents for the
      radioactive decontamination of wet (99m)Tc-pertechnetate spills in the nuclear
      medicine department. METHODS: Six cleaning agents (water, water and soap,
      alcohol, bleach, a commercial glass cleaner, and a commercial decontaminating
      agent) were analyzed for decontamination effectiveness for a wide range of
      surfaces (Formica, vinyl, vinyl-polyester, plastic, rubber, and polyester).
      RESULTS: Within the experiment, the contamination was removed to radioactivity
      levels of less than 1% of the original contamination level. CONCLUSION: The
      results indicate that for a range of surfaces, the investigated commercially
      available cleaning agents had little or no benefit over plain tap water when used
      to decontaminate (99m)Tc-pertechnetate spills.

PMID- 21078782
TI  - SNM practice guideline for hepatobiliary scintigraphy 4.0.

PMID- 21078785
TI  - Mechanisms of amiodarone and desethylamiodarone cytotoxicity in nontransformed
      human peripheral lung epithelial cells.
AB  - Amiodarone (AM) is a potent antidysrhythmic agent that can cause potentially life
      threatening pulmonary fibrosis, and N-desethylamiodarone (DEA), an AM metabolite,
      may contribute to AM toxicity. Apoptotic cell death in nontransformed human
      peripheral lung epithelial 1A (HPL1A) cells was assessed by annexin V-fluorescein
      isothiocyanate (ann-V) staining and terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL), and necrotic cell death was assessed by
      propidium iodide (PI) staining. The percentage of cells that were PI-positive
      increased more than six times with 20 MUM AM and approximately doubled with 3.5
      MUM DEA, relative to control. The percentage of cells that were ann-V-positive
      decreased by more than 80% after 24-h exposure to 10 MUM AM but more than doubled
      after 24-h incubation with 3.5 MUM DEA. Incubation for 24 h with 5.0 MUM DEA
      increased the percentage of cells that were TUNEL-positive more than six times.
      Incubation with AM (2.5 MUM) or DEA (1-2 MUM) for 24 h did not significantly
      alter angiotensinogen mRNA levels. Furthermore, angiotensin II (100 pM-1 MUM)
      alone or in combination with AM or DEA did not alter cytotoxicity, and
      pretreatment with the angiotensin-converting enzyme inhibitor and antioxidant
      captopril (3-6 MUM) did not protect against AM or DEA cytotoxicity. In
      conclusion, AM activates primarily necrotic pathways, whereas DEA activates both
      necrotic and apoptotic pathways, and the renin-angiotensin system does not seem
      to be involved in AM or DEA cytotoxicity in HPL1A cells.

PMID- 21078786
TI  - Endothelial dysfunction in systemic lupus erythematosus: evaluation with 13N
      ammonia PET.
AB  - Systemic lupus erythematosus (SLE) affects multiple organs and systems, severely
      involving the cardiovascular system. The aim of this study was to evaluate the
      presence of endothelial dysfunction with (13)N-ammonia PET in asymptomatic SLE
      patients. METHODS: We enrolled 16 women with SLE and 16 healthy women. Myocardial
      blood flow (MBF) was quantified in a 64-slice PET/CT scanner at rest, during a
      cold pressor test (CPT), and during stress. Endothelium-dependent vasodilation
      index, %DeltaMBF, and myocardial flow reserve (MFR) were calculated. RESULTS:
      There were 16 women in the SLE group (mean age +/- SD, 31.4 +/- 8.3 y) and 16
      women in the healthy control group (31.5 +/- 11.1 y). Mean endothelium-dependent
      vasodilatation index and %DeltaMBF were significantly lower in SLE patients (1.18
      +/- 0.55 vs. 1.63 +/- 0.65, P = 0.04, and 18 +/- 55 vs. 63 +/- 65, P = 0.04,
      respectively). MFR was also lower in the SLE group (2.41 +/- 0.59 vs. 2.73 +/-
      0.77, P = 0.20). CONCLUSION: SLE patients who are free of active disease present
      abnormal coronary flow and endothelial dysfunction. It is necessary to develop
      and intensify treatment strategies directed to CAD in SLE patients.

PMID- 21078787
TI  - 18F-FDG PET/CT for the prediction and detection of local recurrence after
      radiofrequency ablation of malignant lung lesions.
AB  - The utility of (18)F-FDG PET/CT for response assessment in malignant lung tumors
      treated with radiofrequency ablation (RFA) and for the detection and prediction
      of local recurrence was investigated. METHODS: Between December 17, 2003, and
      April 9, 2008, 68 consecutive patients (mean age, 68 y) with 94 pulmonary
      lesions, including metastases (n = 38) and primary lung cancers (n = 44),
      underwent RFA. Because of inadequate imaging follow-up in 12 patients, only 82
      lesions were analyzed (CT scans, n = 82; (18)F-FDG PET/CT scans, n = 62). The
      median follow-up was 25 mo (range, 12-66 mo). A baseline study was defined as
      (18)F-FDG PET/CT performed no more than 3 mo before RFA. The first postablation
      scan was defined as PET/CT performed between 1 and 4 mo after RFA; additional
      follow-up studies were obtained in some cases between 6 and 12 mo after RFA. The
      unidimensional maximum diameter of the lesion was recorded on a pretherapy
      diagnostic CT scan or on the CT component of a pretherapy (18)F-FDG PET/CT scan,
      whichever was obtained most recently, using lung windows. Maximum standardized
      uptake values (SUVs) were recorded for all lesions imaged by (18)F-FDG PET/CT.
      (18)F-FDG uptake patterns on post-RFA scans were classified as favorable or
      unfavorable. Survival and recurrence probabilities were estimated using the
      Kaplan-Meier method. Uni- and multivariate analyses were also performed. RESULTS:
      Before RFA, factors predicting greater local recurrence-free survival included
      initial lesion size less than 3 cm (P = 0.01) and SUV less than 8 (P = 0.02),
      although the latter was not an independent predictor in multivariate analysis.
      Treated metastases recurred less often than treated primary lung cancers (P =
      0.03). Important post-RFA factors that related to reduced recurrence-free
      survival included an unfavorable uptake pattern (P < 0.01), post-RFA SUV (P <
      0.01), and an increase in SUV over time after ablation (P = 0.05). CONCLUSION:
      (18)F-FDG PET/CT parameters on both preablation and postablation scans may
      predict local recurrence in patients treated with RFA for lung metastases and
      primary lung cancers.

PMID- 21078788
TI  - Qualitative and quantitative impact of protective glucocorticoid therapy on the
      effective 131I half-life in radioiodine therapy for Graves disease.
AB  - This aim of this retrospective study was to determine the impact of
      glucocorticoid therapy on the effective (131)I half-life in radioiodine therapy
      for Graves disease. METHODS: Three hundred fifteen consecutive Graves disease
      patients undergoing radioiodine therapy at our institution between August 2004
      and January 2009 were enrolled. We investigated the influences of thyroid state
      (hypothyroidism, euthyroidism, hyperthyroidism), antithyroid drug dose before
      (131)I therapy, thyroid-stimulating hormone receptor antibody (TRAb) level, and
      qualitative and quantitative factors of prednisolone therapy on the effective
      (131)I half-life, applying univariate (paired t test) and multivariate (multiple
      regression) analyses. RESULTS: Multivariate analyses revealed independent
      significant effects of the thyroid metabolic state (P = 0.004), antithyroid drugs
      (P < 0.001), presence of TRAb (P = 0.004), and glucocorticoids (P = 0.046) on
      thyroidal radioiodine half-life. Compared with euthyroidism, thyrotoxicosis and
      hypothyroidism reduced the effective half-life; high doses of antithyroid drugs
      and high TRAb levels had the same effect. Also, glucocorticoid therapy shortened
      the effective thyroidal radioiodine half-life in a dose-dependent manner.
      Pharmacologically, this effect is attributable to the prednisolone-induced
      increase of renal plasma (131)I clearance and the resulting reduction of plasma
      (131)I available for reuptake into the thyroid during radioiodine therapy.
      CONCLUSION: Oral treatment with prednisolone results in a reduction of effective
      thyroidal (131)I half-life in Graves disease, especially at higher doses.

PMID- 21078789
TI  - Improvement of early 18F-FDG PET interpretation in diffuse large B-cell lymphoma:
      importance of the reference background.
AB  - This study investigated whether the reference background above which a residual
      mass is considered positive in the International Harmonization Project criteria
      should be modified for early (18)F-FDG PET evaluation. METHODS: In 92 patients
      with newly diagnosed diffuse large B-cell lymphoma, the maximal standardized
      uptake value (SUVmax) was measured on post-cycle 2 PET in the most intense
      residual mass (or, in the case of negative PET findings, in the area of most
      intense tumor uptake before therapy), in the mediastinal blood pool (MBP) and the
      liver, as potential reference background tissues. RESULTS: With MBP as a
      reference (SUVmax, 2.0 +/- 0.6), PET was unable to distinguish early responders
      from nonresponders. In contrast, with liver as a reference (SUVmax, 2.5 +/- 0.7),
      2-y progression-free survival was significantly different between patients with
      PET-negative findings (81.8% [95% confidence interval, 71%-93%]) and patients
      with PET-positive findings (51.8% [95% confidence interval, 35%-69%], P = 0.003).
      CONCLUSION: When assessing early response, particularly in risk-adapted
      therapeutic trials, it seems preferable to refer to a background tissue (liver)
      with a higher level of uptake than that of current international criteria (MBP)
      which were designed for end-of-treatment evaluation.

PMID- 21078790
TI  - Molecular mechanisms of bone 18F-NaF deposition.
AB  - There is renewed interest in (18)F-NaF bone imaging with PET or PET/CT. The
      current brief discussion focuses on the molecular mechanisms of (18)F-NaF
      deposition in bone and presents model-based approaches to quantifying bone
      perfusion and metabolism in the context of preclinical and clinical applications
      of bone imaging with PET.

PMID- 21078791
TI  - Repeatability of metabolically active volume measurements with 18F-FDG and 18F
      FLT PET in non-small cell lung cancer.
AB  - In addition to tumor size measurements with CT, there is a need for quantitative
      measurements of metabolic active volumes, possibly adding to tracer uptake
      measurements in oncologic response evaluation with PET. The aim of this study was
      to evaluate the metabolic volume test-retest variability in (18)F-FDG and 3'
      deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET studies for various commonly used
      volumes of interest (VOIs) and the dependence of that variability on lesion size
      and relative radiotracer uptake. METHODS: Twenty non-small cell lung cancer
      patients were scanned twice with (18)F-FDG (n = 11) or (18)F-FLT (n = 9). VOIs
      were defined on images reconstructed with normalization- and attenuation-weighted
      ordered-subset expectation maximization using 4 isocontours (A41%, A50%, and A70%
      thresholds, adapted for local background, and 50% threshold, uncorrected for
      background). Statistical analysis comprised intraclass correlation coefficients
      and Bland-Altman analysis. RESULTS: In the (18)F-FDG and (18)F-FLT groups, 34 and
      20 lesions, respectively, were analyzed. Median volumes at the A50% threshold
      were 3.31 and 2.19 mL (interquartile range, 1.91-8.90 and 1.52-7.27 mL) for (18)F
      FDG and (18)F-FLT, respectively. Intraclass correlation coefficients were greater
      than 0.9, with the exception of the A70%-based metabolic volumes for (18)F-FLT.
      For lesions greater than 4.2 mL, repeatability coefficients (RCs = 1.96 * SD) of
      the percentage difference ranged from 22% to 37% for (18)F-FDG and from 39% to
      73% for (18)F-FLT, depending on the VOI method being used. Repeatability was
      better for larger tumors, but there was no dependence on absolute uptake
      (standardized uptake value). CONCLUSION: Results indicate that changes of greater
      than 37% for (18)F-FDG and greater than 73% for (18)F-FLT (1.96 * SD) for lesions
      with A50% metabolic volumes greater than 4.2 mL represent a biologic effect. For
      smaller lesions (A50% VOI < 4.2 mL), an absolute change of 1.0 and 0.9 mL for
      (18)F-FDG and (18)F-FLT, respectively, is biologically relevant. Considering the
      balance between the success rate of automatic tumor delineation and repeatability
      of metabolic volume, a 50% threshold with correction for local background
      activity (A50%) seems optimal among the VOI methods evaluated.

PMID- 21078792
TI  - Restaging: should we percist without pattern recognition?

PMID- 21078793
TI  - Tissue factor detection for selectively discriminating unstable plaques in an
      atherosclerotic rabbit model.
AB  - Tissue factor (TF), a transmembrane glycoprotein that acts as an essential
      cofactor to factor VII/VIIa, initiates the exogenous blood coagulation cascade
      leading to thrombin generation and subsequent thrombus formation in vivo. TF
      expression is closely related to plaque vulnerability, and high TF expression is
      shown in macrophage-rich atheromatous lesions, making TF a potential target for
      detecting atheromatous lesions in vivo. Thus, we prepared (99m)Tc-labeled anti-TF
      monoclonal antibody (TF-mAb) IgG as a molecular probe and evaluated its
      usefulness to achieve TF-specific imaging using myocardial infarction-prone
      Watanabe heritable hyperlipidemic (WHHLMI) rabbits. METHODS: Anti-TF-mAb was
      created using a standard hybridoma technique and was labeled by (99m)Tc with 6
      hydrazinonicotinic acid (HYNIC) as a chelating agent to obtain (99m)Tc-TF-mAb.
      The immunoreactivity of HYNIC-TF-mAb was estimated by flow cytometry. WHHLMI and
      control rabbits were injected intravenously with (99m)Tc-TF-mAb. Twenty-four
      hours after the injection, the aorta was removed and radioactivity was measured.
      Autoradiography and histologic studies were performed using serial aorta
      sections. Subclass matched antibody (IgG(1)) was used as a negative control.
      RESULTS: HYNIC-TF-mAb showed 93% immunoreactivity of the anti-TF-mAb. The
      radioactivity accumulation in WHHLMI aortas was 6.1-fold higher than that of
      control rabbits. Autoradiograms showed a heterogeneous distribution of
      radioactivity in the intima of WHHLMI aortas. Regional radioactivity accumulation
      was positively correlated with TF expression density (R = 0.64, P < 0.0001). The
      highest radioactivity accumulation in percentage injected dose * body
      weight/mm(2) * 10(2) was found in atheromatous lesions (5.2 +/- 1.9) followed by
      fibroatheromatous (2.1 +/- 0.7), collagen-rich (1.8 +/- 0.7), and neointimal
      lesions (1.8 +/- 0.6). In contrast, (99m)Tc-IgG(1) showed low radioactivity
      accumulation in WHHLMI aortas that was independent of the histologic grade of
      lesions. CONCLUSION: The TF-detecting ability and preferential accumulation in
      atheromatous lesions of (99m)Tc-TF-mAb were demonstrated, indicating its
      potential for selective imaging of macrophage-rich atheromatous lesions in vivo.

PMID- 21078794
TI  - 68Ga-DOTANOC PET/CT allows somatostatin receptor imaging in idiopathic pulmonary
      fibrosis: preliminary results.
AB  - Interstitial lung diseases include different clinical entities with variable
      prognoses. Idiopathic pulmonary fibrosis (IPF), the most common, presents the
      most severe outcome (death within 3-5 y), whereas nonspecific interstitial
      pneumonia (NSIP) shows a more indolent progression. Preclinical evidence of
      somatostatin receptor (SSTR) expression on fibroblasts in vitro and in lung
      fibrosis murine models, coupled with the longer survival of mice with fibrotic
      lungs treated with agents blocking SSTR, supports the hypothesis of imaging
      fibroblast activity in vivo by visualization of SSTR with (68)Ga-DOTANOC PET/CT.
      The aim of this study was to evaluate (68)Ga-DOTANOC PET/CT in patients with IPF
      and NSIP. METHODS: Seven IPF patients and 7 NSIP patients were included in the
      study. (68)Ga-DOTANOC PET/CT and high-resolution CT (HRCT) were performed in all
      cases by following a standard procedure. PET/CT results were compared with
      disease sites and extent on HRCT. RESULTS: In IPF, (68)Ga-DOTANOC uptake was
      peripheral, subpleural, and directly correlated with pathologic areas on HRCT
      (subpleural/reticular fibrosis, honeycombing). NSIP patients showed fainter
      tracer uptake, whereas corresponding HRCT showed areas of ground-glass opacity
      and rare fibrotic changes. Only IPF patients showed a linear correlation between
      maximal SUV and disease extent quantified both automatically (Q) (IPF: P = 0.002,
      R = 0.93) and using the visual score (Spearman rho = 0.46, P = 0.0001). Q
      directly correlated with percentage carbon monoxide diffusing capacity in IPF (P
      = 0.03, R = 0.79) and NSIP (P = 0.05, R = 0.94), whereas maximal SUV did not
      present any correlation with percentage carbon monoxide diffusing capacity.
      CONCLUSION: Our preliminary data show that (68)Ga-DOTANOC PET/CT demonstrates
      SSTR overexpression in IPF patients; this may prove interesting for the
      evaluation of novel treatments with somatostatin analogs.

PMID- 21078795
TI  - Dynamic and static small-animal SPECT in rats for monitoring renal function after
      177Lu-labeled Tyr3-octreotate radionuclide therapy.
AB  - High kidney radiation doses during clinical peptide receptor radionuclide therapy
      (PRRT) with beta-particle-emitting radiolabeled somatostatin analogs will lead to
      renal failure several months after treatment, urging the coinfusion of the
      cationic amino acids lysine and arginine to reduce the renal radiation dose. In
      rat PRRT studies, renal protection by the coadministration of lysine was
      confirmed by histologic examination of kidney specimens indicating
      nephrotoxicity. In the current study, we investigated dedicated small-animal
      SPECT/CT renal imaging in rats to monitor renal function in vivo during follow-up
      of PRRT, with and without lysine. METHODS: The following 3 groups of rats were
      imaged using a multipinhole SPECT/CT camera: controls (group 1) and rats at more
      than 90 d after therapy with 460 MBq (15 MUg) of (177)Lu-DOTA-Tyr(3)-octreotate
      without (group 2) or with (group 3) a 400-mg/kg lysine coinjection as kidney
      protection (n >= 6 per group). At 90 and 140 d after therapy, static kidney
      scintigraphy was performed at 2 h after injection of 25 MBq of (99m)Tc
      dimercaptosuccinic acid ((99m)Tc-DMSA). In addition, dynamic dual-isotope
      renography was performed using 50 MBq of (111)In-diethylenetriaminepentaacetic
      acid ((111)In-DTPA) and 50 MBq of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3)
      at 100-120 d after therapy. RESULTS: (111)In-DTPA and (99m)Tc-MAG3 studies
      revealed a time-activity pattern comparable to those in patients, with a peak at
      2-6 min followed by a decline of renal radioactivity. Reduced (111)In-DTPA,
      (99m)Tc-MAG3, and (99m)Tc-DMSA uptake indicated renal damage in group 2, whereas
      group 3 showed only a decrease of (99m)Tc-MAG3 peak activity. These results
      indicating nephrotoxicity in group 2 and renal protection in group 3 correlated
      with levels of urinary protein and serum creatinine and urea and were confirmed
      by renal histology. CONCLUSION: Quantitative dynamic dual-isotope imaging using
      both (111)In-DTPA and (99m)Tc-MAG3 and static (99m)Tc-DMSA imaging in rats is
      feasible using small-animal SPECT, enabling longitudinal monitoring of renal
      function. (99m)Tc-MAG3 renography, especially, appears to be a more sensitive
      marker of tubular function after PRRT than serum chemistry or (99m)Tc-DMSA
      scintigraphy.

PMID- 21078796
TI  - Early repeated 18F-FDG PET scans during neoadjuvant chemoradiation fail to
      predict histopathologic response or survival benefit in adenocarcinoma of the
      esophagus.
AB  - This study evaluated the role of (18)F-FDG PET as an early predictor of
      histopathologic response to neoadjuvant chemoradiotherapy and overall survival in
      patients with adenocarcinoma of the esophagus undergoing multimodal therapy.
      METHODS: Thirty-seven patients with locally advanced adenocarcinoma of the
      esophagus underwent pretreatment and an intratreatment (18)F-FDG PET scan in the
      second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic
      response and overall survival were correlated with percentage change in (18)F-FDG
      uptake (%Deltamaximum standardized uptake value [%DeltaSUVmax]). RESULTS: In 16
      patients (43%), treatment induced a histopathologic response (<10% viable tumor
      cells), which was associated with a significant (P < 0.05) survival benefit. The
      optimal reduction in (18)F-FDG uptake, which separated histopathologic responders
      and nonresponders, was a -26.4% DeltaSUVmax (receiver-operating-characteristic
      curve analysis). At this separation, sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy (area under the
      receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and
      67.4%, respectively, for intratreatment (18)F-FDG PET scans. Kaplan-Meier
      survival analysis of (18)F-FDG PET responders (>26.4% reduction in SUVmax),
      compared with (18)F-FDG PET nonresponders (<26.4% reduction in SUVmax), revealed
      no survival benefit for responders (P = 0.6812). CONCLUSION: The %DeltaSUVmax
      during the second week of induction chemoradiation did not correlate either with
      histopathologic response or with survival. Our results show that, in contrast to
      published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in
      patients with adenocarcinoma of the esophagus lowers the predictive accuracy of
      early repeated (18)F-FDG PET in identifying histopathologic responders and those
      with chances for increased survival below clinically applicable levels.

PMID- 21078797
TI  - The value of 99mTc-tetrofosmin brain SPECT in predicting survival in patients
      with glioblastoma multiforme.
AB  - (99m)Tc-tetrofosmin brain SPECT has been reported as a useful tool for the
      evaluation of glioma proliferation. In the present study, we set out to
      investigate the prognostic value of (99m)Tc-tetrofosmin brain SPECT in patients
      with glioblastoma multiforme. METHODS: We prospectively studied 18 patients (13
      men, 5 women; mean age +/- SD, 60.8 +/- 7.79 y) who were operated on for
      glioblastoma multiforme. All patients underwent preoperative (99m)Tc-tetrofosmin
      brain SPECT, and surgical excision was performed within a week after SPECT. All
      patients received postoperative radiotherapy and chemotherapy. RESULTS: By
      calculating the lesion-to-normal (L/N) (99m)Tc-tetrofosmin uptake ratio, we found
      that patients with an L/N ratio of more than 4.7 had significantly worse survival
      than did patients with an L/N ratio of 4.7 or less. Furthermore, patients with a
      Karnofsky Performance Score more than 90 had a significantly better survival
      rate. Although patients with near-total tumor resection who were younger than 60
      y survived longer, the difference did not reach statistical significance. In the
      multivariate analysis, (99m)Tc-tetrofosmin uptake and Karnofsky Performance Score
      were identified as factors with independent prognostic power. CONCLUSION: (99m)Tc
      tetrofosmin brain SPECT may be an independent prognostic factor in patients with
      glioblastoma multiforme. Further larger studies are needed to verify these
      results.

PMID- 21078798
TI  - Imaging of inflammation by PET, conventional scintigraphy, and other imaging
      techniques.
AB  - Nuclear medicine imaging procedures play an important role in the assessment of
      inflammatory diseases. With the advent of 3-dimensional anatomic imaging, there
      has been a tendency to replace traditional planar scintigraphy by CT or MRI.
      Furthermore, scintigraphic techniques may have to be combined with other imaging
      modalities to achieve high sensitivity and specificity, and some may require time
      consuming labeling procedures. On the other hand, new developments such as
      combined SPECT/CT increase the diagnostic power of scintigraphy. Also, the advent
      of PET had a considerable impact on the use of nuclear medicine imaging
      techniques. In this review, we aim to provide nuclear medicine specialists and
      clinicians with the relevant information on rational and efficient use of nuclear
      medicine imaging techniques in the assessment of patients with osteomyelitis,
      infected vascular prostheses, metastatic infectious disease, rheumatoid
      arthritis, vasculitis, inflammatory bowel disease, sarcoidosis, and fever of
      unknown origin.

PMID- 21078799
TI  - 90Y Bremsstrahlung imaging for absorbed-dose assessment in high-dose
      radioimmunotherapy.
AB  - This feasibility study demonstrates (90)Y quantitative bremsstrahlung imaging of
      patients undergoing high-dose myeloablative (90)Y-ibritumomab treatment. METHODS:
      The study includes pretherapy (111)In SPECT/CT and planar whole-body (WB) imaging
      at 7 d and therapy (90)Y SPECT/CT at 6 d and (90)Y WB imaging at 1 d. Time
      activity curves and organ-absorbed doses derived from (90)Y SPECT images were
      compared with pretherapy (111)In estimates. Organ activities derived from (90)Y
      WB images at the first day were compared with corresponding pretherapy estimates.
      RESULTS: Pretherapy (111)In images from 3 patients were similar to the (90)Y
      images. Differences between absorbed-dose estimates from pretherapy (111)In and
      (90)Y therapy were within 25%, except for the lungs. Corresponding activity
      differences derived from WB images were within 25%. Differences were ascribed to
      incomplete compensation methods and real differences in pharmacokinetics between
      pretherapy and therapy. CONCLUSION: Quantitative bremsstrahlung imaging to
      estimate organ activities and absorbed doses is feasible.

PMID- 21078800
TI  - Radionuclide imaging of angiotensin II type 1 receptor upregulation after
      myocardial ischemia-reperfusion injury.
AB  - The renin-angiotensin system (RAS) mediates proapoptotic, profibrotic, and
      proinflammatory processes in maladaptive conditions. Activation after myocardial
      infarction may initialize and promote cardiac remodeling. Using a novel positron
      emitting ligand, we sought to determine the presence and time course of regional
      myocardial upregulation of the angiotensin II type 1 receptor (AT1R) and the
      blocking efficacy of various anti-RAS agents. METHODS: In male Wistar rats (n =
      31), ischemia-reperfusion damage was induced by 20- to 25-min ligation of the
      left coronary artery. The AT1R blocker (11)C-2-butyl-5-methoxymethyl-6-(1
      oxopyridin-2-yl)-3-[[2-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-3H-imidazo[4,5
      b]pyridine ((11)C-KR31173) was injected intravenously at different times until 6
      mo after surgery and sacrifice. Autoradiography, histology, and
      immunohistochemistry were performed for ex vivo validation. Additional in vivo
      PET was conducted in 3 animals. A second series of experiments (n = 16) compared
      untreated animals with animals treated with oral valsartan (50 mg/kg/d), oral
      enalapril (10 mg/kg/d), and complete intravenous blockage (SK-1080, 2 mg/kg, 10
      min before imaging). RESULTS: Transient regional AT1R upregulation was detected
      in the infarct area, with a peak at 1-3 wk after surgery (autoradiographic
      infarct-to-remote ratio, 1.07 +/- 0.09, 1.68 +/- 0.34, 2.54 +/- 0.40, 2.98 +/-
      0.70, 3.16 +/- 0.57, 1.86 +/- 0.65, and 1.28 +/- 0.27 at control, day 1, day 3,
      week 1, week 3, month 3, and month 6, respectively). The elevated uptake of (11)C
      KR31173 in the infarct area was detectable by small-animal PET in vivo, and it
      was blocked completely by intravenous SK-1080. Although oral treatment with
      enalapril did not reduce focal tracer uptake, oral valsartan resulted in partial
      blockade (infarct-to-remote ratio, 2.94 +/- 0.52, 2.88 +/- 0.60, 2.07 +/- 0.25,
      and 1.26 +/- 0.10 for no treatment, enalapril, valsartan, and SK-1080,
      respectively). CONCLUSION: After ischemic myocardial damage in a rat model,
      transient regional AT1R upregulation is detectable in the infarct area using
      (11)C-KR31173. Inhibitory effects of the clinical AT1R blocker valsartan can be
      identified, whereas blockage of upstream angiotensin-converting enzyme with
      enalapril does not affect AT1R density. These results provide a rationale for
      subsequent testing of AT1R-targeted imaging to predict the risk for ventricular
      remodeling and to monitor the efficacy of anti-RAS drug therapy.

PMID- 21078802
TI  - 4-Step renal dosimetry dependent on cortex geometry applied to 90Y peptide
      receptor radiotherapy: evaluation using a fillable kidney phantom imaged by 90Y
      PET.
AB  - Accurate dosimetry in (90)Y peptide receptor radionuclide therapy (PRRT) helps to
      optimize the injected activity, to prevent kidney or red marrow toxicity, while
      giving the highest absorbed dose to tumors. The aim of this study was to evaluate
      whether direct (90)Y bismuth germanate or lutetium yttrium orthosilicate time-of
      flight PET was accurate enough to provide dosimetry estimates suitable to (90)Y
      PRRT. METHOD: To overcome the statistical uncertainty arising from the low (90)Y
      positron counting rate, the computation of the cortex mean-absorbed dose was
      divided into 4 steps: delineation of the cortex volume of interest (VOI) on the
      CT scan, determination of the recovery coefficient from the cortex VOI using the
      point-spread function of the whole imaging process, determination of the mean
      cortex-absorbed dose per unit cumulated activity in the cortex (S(cortex<-cortex)
      value) from the cortex VOI using a (90)Y voxel S value kernel, and determination
      of the number of decays in the cortex VOI from the PET reconstruction. Our 4-step
      method was evaluated using an anthropomorphic abdominal phantom containing a
      fillable kidney phantom based on the MIRD kidney model. Vertebrae with an
      attenuation similar to that of bone were also modeled. Two tumors were modeled by
      7-mL hollow acrylic spheres and the spleen by a plastic bag. Activities
      corresponded to typical tissue uptake in a first (90)Y-DOTATOC cycle of 4.4 GBq,
      considered as free of significant renal toxicity. Eight successive 45-min scans
      were acquired on both systems. RESULTS: Both PET systems were successful in
      determining absorbed dose to modeled tumors but failed to provide accurate red
      marrow dosimetry. Renal cortex dosimetry was reproducible for both PET systems,
      with an accuracy of 3% for the bismuth germanate system but only 18% for the
      lutetium yttrium orthosilicate time-of-flight system, which was hindered by the
      natural radioactivity of the crystal, especially in the most attenuated area of
      the kidney. CONCLUSION: This study supports the use of direct (90)Y PET of the
      first PRRT cycle to assess the kidney-absorbed dose and optimize the injected
      activity of the following cycles.

PMID- 21078801
TI  - 68Ga-citrate PET/CT for evaluating patients with infections of the bone:
      preliminary results.
AB  - The aim of this work was to preliminarily evaluate the sensitivity, specificity,
      positive predictive value, negative predictive value, and overall accuracy of
      (68)Ga-citrate PET/CT in a population of patients with suspected bone infections.
      METHODS: We enrolled 31 patients with suspected osteomyelitis or diskitis who
      underwent a total of forty (68)Ga-citrate PET/CT scans. The results were compared
      with different combinations of diagnostic procedures (MRI, radiography, CT, or
      white blood cell scintigraphy), biopsy (when diagnostic), and follow-up data (at
      least 1 y) to determine the performance of (68)Ga-citrate PET/CT. RESULTS: We
      found a sensitivity of 100%, a specificity of 76%, a positive predictive value of
      85%, a negative predictive value of 100%, and an overall accuracy of 90%.
      CONCLUSION: Although preliminary, these data confirm a possible role for (68)Ga
      citrate in the diagnosis of bone infections, especially in consideration of its
      favorable characteristics.

PMID- 21078803
TI  - Low-dose 18F-FDG PET/CT enterography: improving on CT enterography assessment of
      patients with Crohn disease.
AB  - The purpose of this study was to evaluate the diagnostic efficacy of low-dose,
      combined (18)F-FDG PET/CT enterography (PET/CTE), compared with CT enterography
      (CTE) alone, in the assessment of patients with Crohn disease. METHODS: Thirteen
      patients with Crohn disease were prospectively enrolled in this pilot study and
      underwent abdominal-pelvic (18)F-FDG PET/CTE using neutral oral and intravenous
      contrast medium. The effective dose from PET/CTE was 17.7 mSv for the first 4
      patients and 8.31 mSv for the last 9 patients. Six patients underwent surgical
      resection of the bowel, and 7 patients underwent colonoscopy with biopsies within
      27 d (mean, 12 d) of PET/CTE. PET/CTE and CTE images were each visually assessed
      for Crohn disease involvement in 54 bowel segments with pathology correlation.
      Extraintestinal findings were recorded. A CTE severity score, maximum
      standardized uptake value (SUVmax), SUVmax ratio, simplified endoscopic score,
      and clinical parameters were correlated with pathology inflammation grade, on a
      per-patient basis and on a per-bowel-segment basis, using Spearman correlation.
      RESULTS: In 3 (23.1%) of 13 patients, (18)F-FDG uptake using PET/CTE revealed
      active inflammation in a bowel segment not evident using CTE (n = 2) or revealed
      an enterocolic fistula missed with CTE (n = 1). Visual interpretation of both
      PET/CTE and CTE images detected the presence of disease in all bowel segments
      with more than mild inflammation (sensitivity, 100%; specificity, 89.7%; positive
      predictive value, 78.9%; and negative predictive value, 100%). Correlation to
      inflammation grade per patient was the strongest for the SUVmax ratio (0.735, P =
      0.004) and SUVmax (0.67, P = 0.013), as compared with the CTE score (0.62, P =
      0.024). Correlation with inflammation per bowel segment was higher for the CTE
      score (0.79, P < 0.0001) than the SUVmax ratio (0.62, P < 0.0001) or SUVmax
      (0.48, P < 0.0001). SUVmax correlated strongly with serum C-reactive protein
      (0.82, P = 0.023), but CTE score did not. CONCLUSION: Low-dose (18)F-FDG PET/CTE,
      compared with CTE, may improve the detection and grading of active inflammation
      in patients with Crohn disease. PET/CTE also may reveal clinically significant
      findings, such as enterocolic fistula, not evident on PET or CTE alone.

PMID- 21078804
TI  - The role of PET with 13N-ammonia and 18F-FDG in the assessment of myocardial
      perfusion and metabolism in patients with recent AMI and intracoronary stem cell
      injection.
AB  - Over the last decade, the effects of stem cell therapy on cardiac repair after
      acute myocardial infarction (AMI) have been investigated with different imaging
      techniques. We evaluated a new imaging approach using (13)N-ammonia and (18)F-FDG
      PET for a combined analysis of cardiac perfusion, metabolism, and function in
      patients treated with intracoronary injection of endothelial progenitors or with
      conventional therapy for AMI. METHODS: A total of 15 patients were randomly
      assigned to 3 groups based on different treatments (group A: bone marrow-derived
      stem cells; group B: peripheral blood-derived stem cells; group C: standard
      therapy alone). The number of scarred and viable segments, along with the infarct
      size and the extent of the viable area, were determined on a 9-segment (13)N
      ammonia/(18)F-FDG PET polar map. Myocardial blood flow (MBF) was calculated for
      each segment on the ammonia polar map, whereas a global evaluation of left
      ventricular function was obtained by estimating left ventricular ejection
      fraction (LVEF) and end-diastolic volume, both derived from electrocardiography
      gated (18)F-FDG images. Both intragroup and intergroup comparative analyses of
      the mean values of each parameter were performed at baseline and 3, 6, and 12 mo
      after AMI. During follow-up, major cardiac events were also registered. RESULTS:
      A significant decrease (P < 0.05) in the number of scarred segments and infarct
      size was observed in group A, along with an increase in MBF (P < 0.05) and a mild
      improvement in cardiac function. Lack of infarct size shrinkage in group B was
      associated with a marked impairment of MBF (P = 0.01) and cardiac dysfunction.
      Ambiguous changes in infarct size, MBF, and LVEF were found in group C. No
      differences in number of viable segments or in extent of viable area were found
      among the groups. At clinical follow-up, no major cardiac events occurred in
      group A patients, whereas 2 patients of group B experienced in-stent occlusion
      and one patient of group C received a transplant for heart failure. CONCLUSION:
      Our data suggest that a single nuclear imaging technique accurately analyzes
      changes in myocardial perfusion and metabolism occurring after stem cell
      transplantation.

PMID- 21078805
TI  - Objective detection of epileptic foci by 18F-FDG PET in children undergoing
      epilepsy surgery.
AB  - PET has been used for the presurgical localization of epileptic foci for more
      than 20 y; still, its clinical role in children with intractable epilepsy remains
      unclear, largely because of variable analytic approaches and different outcome
      measures. The purpose of the present study was to evaluate and optimize the
      performance (lateralization and lobar localization value of epileptic foci) of
      objective voxel-based analysis of (18)F-FDG PET scans in a pediatric epilepsy
      population. METHODS: Twenty children with intractable focal epilepsy (mean age +/
      SD, 11 +/- 4 y; age range, 6-18 y) who underwent interictal (18)F-FDG PET,
      followed by 2-stage epilepsy surgery with chronic subdural electrocorticographic
      monitoring, and were seizure-free after surgery were included in this study. PET
      images were analyzed using both a visual-analysis and a statistical parametric
      mapping (SPM) method. Lateralization value and performance of lobar localization
      (in lateral and medial surfaces of all lobes, total of 8 regions in each
      epileptic hemisphere), calculated for 3 different statistical thresholds, were
      determined against intracranial electrocorticography-determined seizure-onset
      region and surgical resection site. RESULTS: SPM using a statistical threshold of
      P less than 0.001 provided 100% correct lateralization, which was better than
      visual assessment (90%). Although visual and SPM analyses (with both P < 0.001
      and P < 0.0001 thresholds) performed similarly well (with a sensitivity and
      specificity of 74% or above) in the localization of seizure-onset regions, SPM
      detected 7 of 9 seizure-onset regions, mostly in medial cortices, that were
      missed by visual assessment. Also, SPM performed equally well in both
      hemispheres, compared with visual analysis, which performed better in the left
      hemisphere. No statistical difference in performance was observed between visual
      and SPM analyses of children with abnormal versus normal MRI findings or of
      children with gliosis versus developmental pathology. Clinical variables, such as
      age, duration of epilepsy, age of seizure onset, and time between PET and last
      seizure, showed no correlation with sensitivity or specificity of either visual
      analysis or SPM analysis. CONCLUSION: SPM analysis, using a young adult control
      group, can be used as a complementary objective analytic method in identifying
      epileptogenic lobar regions by (18)F-FDG PET in children older than 6 y.

PMID- 21078806
TI  - Serotonin transporters in dopamine transporter imaging: a head-to-head comparison
      of dopamine transporter SPECT radioligands 123I-FP-CIT and 123I-PE2I.
AB  - Current SPECT radioligands available for in vivo imaging of the dopamine
      transporter (DAT) also show affinity for monoamine transporters other than DAT,
      especially the serotonin transporter (SERT). The effect of this lack of
      selectivity for in vivo imaging is unknown. In this study, we compared the SPECT
      radioligands (123)I-2-beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3
      fluoropropyl)nortropane ((123)I-FP-CIT) and (123)I-N-(3-iodoprop-2E-enyl)-2-beta
      carbomethoxy-3beta-(4-methylphenyl) nortropane ((123)I-PE2I), which has a 10-fold
      higher selectivity than (123)I-FP-CIT for DAT versus SERT [corrected]. METHODS:
      Sixteen healthy individuals were scanned in random order with both radioligands.
      The radioligands were administered according to standard recommendations: (123)I
      FP-CIT was given as a bolus injection, and the ratio between the striatum and
      reference tissue was measured after 3 h. (123)I-PE2I was administered in a bolus
      infusion setup, and the nondisplaceable binding potential (BP(ND)) was measured
      after 2 h. To assess the contribution of SERT to the overall SPECT signal, SERT
      was blocked by intravenous citalopram in 6 of the individuals. RESULTS: The
      striatum-to-reference ratio - 1 of (123)I-FP-CIT was on average 18% higher than
      the striatal BP(ND) of (123)I-PE2I. Equal doses of radioactivity resulted in 3
      times higher counting rates for (123)I-FP-CIT than for (123)I-PE2I, both in
      target and in reference brain regions. Citalopram infusion led to significant
      reductions in both striatal (22.8% +/- 20.4%, P < 0.05) and thalamic (63.0% +/-
      47.9%, P < 0.05) (123)I-FP-CIT binding ratios, whereas BP(ND) of (123)I-PE2I was
      unaltered. Likewise, blocking of SERT led to increased (21% +/- 30.1%, P < 0.001)
      plasma (123)I-FP-CIT, probably as a result of significant blocking of peripheral
      SERT binding sites. By contrast, plasma (123)I-PE2I remained stable. CONCLUSION:
      (123)I-FP-CIT and (123)I-PE2I had approximately the same target-to-background
      ratios, but per injected megabecquerel, (123)I-FP-CIT gave rise to 3-fold higher
      cerebral counting rates. We found that (123)I-FP-CIT, but not (123)I-PE2I, brain
      images have a highly interindividual but significant signal contribution from
      SERT. Whether the SERT signal contribution is of clinical importance needs to be
      established in future patient studies.

PMID- 21078807
TI  - Multiple testing, cumulative radiation dose, and clinical indications in patients
      undergoing myocardial perfusion imaging.
AB  - CONTEXT: Myocardial perfusion imaging (MPI) is the single medical test with the
      highest radiation burden to the US population. Although many patients undergoing
      MPI receive repeat MPI testing, or additional procedures involving ionizing
      radiation, no data are available characterizing their total longitudinal
      radiation burden and relating radiation burden with reasons for testing.
      OBJECTIVES: To characterize procedure counts, cumulative estimated effective
      doses of radiation, and clinical indications for patients undergoing MPI. DESIGN,
      SETTING, AND PATIENTS: A retrospective cohort study of 1097 consecutive patients
      undergoing index MPI during the first 100 days of 2006 (January 1-April 10) at
      Columbia University Medical Center, New York, New York, that evaluated all
      preceding medical imaging procedures involving ionizing radiation undergone
      beginning October 1988, and all subsequent procedures through June 2008, at the
      center. MAIN OUTCOME MEASURES: Cumulative estimated effective dose of radiation,
      number of procedures involving radiation, and indications for testing. RESULTS:
      Patients underwent a median of 15 (interquartile range [IQR], 6-32; mean, 23.9)
      procedures involving radiation exposure; of which 4 (IQR, 2-8; mean, 6.5) were
      high-dose procedures (>=3 mSv; ie, 1 year's background radiation), including 1
      (IQR, 1-2; mean, 1.8) MPI study per patient. A total of 344 patients (31.4%)
      received cumulative estimated effective dose from all medical sources of more
      than 100 mSv. Multiple MPIs were performed in 424 patients (38.6%), for whom
      cumulative estimated effective dose was 121 mSv (IQR, 81-189; mean, 149 mSv). Men
      and white patients had higher cumulative estimated effective doses. More than 80%
      of initial and 90% of repeat MPI examinations were performed in patients with
      known cardiac disease or symptoms consistent with it. CONCLUSION: In this
      institution, multiple testing with MPI was common and in many patients associated
      with high cumulative estimated doses of radiation.

PMID- 21078808
TI  - Automated external defibrillators and the law of unintended consequences.

PMID- 21078809
TI  - Automated external defibrillators and survival after in-hospital cardiac arrest.
AB  - CONTEXT: Automated external defibrillators (AEDs) improve survival from out-of
      hospital cardiac arrests, but data on their effectiveness in hospitalized
      patients are limited. OBJECTIVE: To evaluate the association between AED use and
      survival for in-hospital cardiac arrest. DESIGN, SETTING, AND PATIENTS: Cohort
      study of 11,695 hospitalized patients with cardiac arrests between January 1,
      2000, and August 26, 2008, at 204 US hospitals following the introduction of AEDs
      on general hospital wards. MAIN OUTCOME MEASURE: Survival to hospital discharge
      by AED use, using multivariable hierarchical regression analyses to adjust for
      patient factors and hospital site. RESULTS: Of 11,695 patients, 9616 (82.2%) had
      nonshockable rhythms (asystole and pulseless electrical activity) and 2079
      (17.8%) had shockable rhythms (ventricular fibrillation and pulseless ventricular
      tachycardia). AEDs were used in 4515 patients (38.6%). Overall, 2117 patients
      (18.1%) survived to hospital discharge. Within the entire study population, AED
      use was associated with a lower rate of survival after in-hospital cardiac arrest
      compared with no AED use (16.3% vs 19.3%; adjusted rate ratio [RR], 0.85; 95%
      confidence interval [CI], 0.78-0.92; P < .001). Among cardiac arrests due to
      nonshockable rhythms, AED use was associated with lower survival (10.4% vs 15.4%;
      adjusted RR, 0.74; 95% CI, 0.65-0.83; P < .001). In contrast, for cardiac arrests
      due to shockable rhythms, AED use was not associated with survival (38.4% vs
      39.8%; adjusted RR, 1.00; 95% CI, 0.88-1.13; P = .99). These patterns were
      consistently observed in both monitored and nonmonitored hospital units where
      AEDs were used, after matching patients to the individual units in each hospital
      where the cardiac arrest occurred, and with a propensity score analysis.
      CONCLUSION: Among hospitalized patients with cardiac arrest, use of AEDs was not
      associated with improved survival.

PMID- 21078810
TI  - Efficacy and safety of prescription omega-3 fatty acids for the prevention of
      recurrent symptomatic atrial fibrillation: a randomized controlled trial.
AB  - CONTEXT: Atrial fibrillation (AF) is common, yet there remains an unmet medical
      need for additional treatment options. Current pharmacological treatments have
      limited efficacy and significant adverse events. Limited data from small trials
      suggest omega-3 polyunsaturated fatty acids may provide a safe, effective
      treatment option for AF patients. OBJECTIVE: To evaluate the safety and efficacy
      of prescription omega-3 fatty acids (prescription omega-3) for the prevention of
      recurrent symptomatic AF. DESIGN, SETTING, AND PARTICIPANTS: Prospective,
      randomized, double-blind, placebo-controlled, parallel-group multicenter trial
      involving 663 US outpatient participants with confirmed symptomatic paroxysmal (n
      = 542) or persistent (n = 121) AF, with no substantial structural heart disease,
      and in normal sinus rhythm at baseline were recruited from November 2006 to July
      2009 (final follow-up was January 2010). INTERVENTIONS: Prescription omega-3 (8
      g/d) or placebo for the first 7 days; prescription omega-3 (4 g/d) or placebo
      thereafter through week 24. MAIN OUTCOME MEASURES: The primary end point was
      symptomatic recurrence of AF (first recurrence) in participants with paroxysmal
      AF. Secondary analyses included first recurrence in the persistent stratum and
      both strata combined. Participants were followed up for 6 months. RESULTS: At 24
      weeks, in the paroxysmal AF stratum, 129 of 269 participants (48%) in the placebo
      group and 135 of 258 participants (52%) in the prescription group had a recurrent
      symptomatic AF or flutter event. In the persistent AF stratum, 18 participants
      (33%) in the placebo group and 32 (50%) in the prescription group had documented
      symptomatic AF or flutter events. There was no difference between treatment
      groups for recurrence of symptomatic AF in the paroxysmal stratum (hazard ratio
      [HR], 1.15; 95% confidence interval [CI], 0.90-1.46; P = .26), in the persistent
      stratum (HR, 1.64; 95% CI, 0.92-2.92; P = .09), and both strata combined (HR,
      1.22; 95% CI, 0.98-1.52; P = .08). Other, secondary end points were supportive of
      the primary result. A total of 5% of those receiving placebo and 4% of those
      receiving prescription omega-3 discontinued due to adverse events.
      Eicosapentaenoic and docosahexaenoic acid blood levels were significantly higher
      in the prescription group than in the placebo group at weeks 4 and 24.
      CONCLUSION: Among participants with paroxysmal AF, 24-week treatment with
      prescription omega-3 compared with placebo did not reduce recurrent AF over 6
      months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402363.

PMID- 21078811
TI  - Association of serial measures of cardiac troponin T using a sensitive assay with
      incident heart failure and cardiovascular mortality in older adults.
AB  - CONTEXT: Older adults comprise the majority of new-onset heart failure (HF)
      diagnoses, but traditional risk-factor prediction models have limited accuracy in
      this population to identify those at highest risk for hospitalization or death.
      OBJECTIVES: To determine if cardiac troponin T (cTnT) measured by a highly
      sensitive assay would be detectable in the majority of community-dwelling older
      adults, and if serial measures were associated with risk of HF hospitalization
      and cardiovascular death. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal
      nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling
      adults aged 65 years or older without prior HF who had cTnT measured using a
      highly sensitive assay at baseline (1989-1990) and repeated after 2 to 3 years (n
      = 2918). MAIN OUTCOME MEASURES: New-onset HF and cardiovascular death were
      examined through June 2008 with respect to cTnT concentrations, accounting for
      clinical risk predictors. RESULTS: Cardiac troponin T was detectable (>=3.00
      pg/mL) in 2794 participants (66.2%). During a median follow-up of 11.8 years,
      1279 participants experienced new-onset HF and 1103 cardiovascular deaths
      occurred, with a greater risk of both end points associated with higher cTnT
      concentrations. Among those participants with the highest cTnT concentrations
      (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95%
      confidence interval [CI], 5.8-7.2; adjusted hazard ratio [aHR], 2.48; 95% CI,
      2.04-3.00) for HF and an incidence rate of 4.8 (95% CI, 4.3-5.4; aHR, 2.91; 95%
      CI, 2.37-3.58) for cardiovascular death compared with participants with
      undetectable cTnT levels (incidence rate, 1.6; 95% CI, 1.4-1.8 and 1.1; 95% CI,
      0.9-1.2 for HF and cardiovascular death, respectively). Among individuals with
      initially detectable cTnT, a subsequent increase of more than 50% (n = 393, 22%)
      was associated with a greater risk for HF (aHR, 1.61; 95% CI, 1.32-1.97) and
      cardiovascular death (aHR, 1.65; 95% CI, 1.35-2.03) and a decrease of more than
      50% (n = 247, 14%) was associated with a lower risk for HF (aHR, 0.73; 95% CI,
      0.54-0.97) and cardiovascular death (aHR, 0.71; 95% CI, 0.52-0.97) compared with
      participants with 50% or less change. Addition of baseline cTnT measurements to
      clinical risk factors was associated with only modest improvement in
      discrimination, with change in C statistic of 0.015 for HF and 0.013 for
      cardiovascular death. CONCLUSION: In this cohort of older adults without known
      HF, baseline cTnT levels and changes in cTnT levels measured with a highly
      sensitive assay were significantly associated with incident HF and cardiovascular
      death.

PMID- 21078813
TI  - Simultaneous use of erythropoietin and prior bleeding enhances the sensitivity of
      the peripheral blood micronucleus assay.
AB  - Adult rats are generally not considered as a suitable model for the peripheral
      blood micronucleus (PBMN) assay in regulatory consideration, owing to the splenic
      removal of the micronucleated cells from circulation. Although prior bleeding
      (PrB) increases the sensitivity of the PBMN assay in young rats, the volume of
      bleeding and the associated stress caused are major concerns for its possible use
      in genotoxicity studies. The present study was aimed to overcome these
      limitations in using pre-bled young rats in genotoxicity studies. The bleeding
      volume was reduced by the simultaneous use of erythropoietin (EPO) to increase
      the sensitivity of PBMN assay. Young Sprague-Dawley (SD, 26 days) rats were used
      in the study. The kinetics of RETs-to-ERTs ratio was determined in response to
      EPO (10-3000 IU/kg) or PrB (0.1-1.0 ml) at different time points (0, 6, 12, 24,
      36, 48, 72 and 96 h). Injection of EPO (30 IU/kg) and PrB (0.5 ml) led to a
      significant increase in the MN frequency in the PBMN assay in response to
      cyclophosphamide and zidovudine. The effect of EPO treatment and/or PrB on cell
      viability and proliferation in the bone marrow (BM) was examined. The results of
      the present study clearly demonstrate that the simultaneous use of both EPO and
      PrB enhances the sensitivity of the PBMN assay in young rats due to increased
      cellular proliferation in the BM. This may provide a useful experimental model
      for the evaluation of marginally active genotoxicants.

PMID- 21078812
TI  - Genesis of phase 3 early afterdepolarizations and triggered activity in acquired
      long-QT syndrome.
AB  - BACKGROUND: Both phase 2 and phase 3 early afterdepolarizations (EADs) occur in
      long-QT syndromes, but their respective roles in generating arrhythmias in intact
      cardiac tissue are incompletely understood. METHODS AND RESULTS: Intracellular Ca
      (Ca(i)) and membrane voltage (V(m)) were optically mapped in a quasi 2
      dimensional model of cryoablated Langendorff-perfused rabbit ventricles (n=16). E
      4031 (an I(Kr) blocker) combined with reduced extracellular K ([K(+)](o)) and Mg
      ([Mg(2+)](o)) prolonged action potential duration heterogeneously and induced
      phase 2 and phase 3 EADs. Whereas phase 2 EADs were Ca(i)-dependent, phase 3 EADs
      were not. The origins of 47 triggered activity episodes were attributed to phase
      2 EADs in 12 episodes (26%) and phase 3 EADs in 35 episodes (74%). When phase 2
      EADs accompanied phase 3 EADs, they accentuated action potential duration
      heterogeneity, creating a large V(m) gradient across the boundary between long
      and short action potential duration regions from which triggered activity
      emerged. The amplitude of phase 3 EADs correlated with the V(m) gradient
      (r=0.898, P<0.001). Computer simulation studies showed that coupling of cells
      with heterogeneous repolarization could extrinsically generate phase 3 EADs via
      electrotonic current flow. Alternatively, reduced I(K1) caused by low [K(+)](o)
      could generate intrinsic phase 3 EADs capable of inducing triggered activity at
      the boundary zone. CONCLUSIONS: Phase 3 EADs can be extrinsic as the result of
      electrotonic current across steep repolarization gradients or intrinsic as the
      result of low I(K1) and do not require spontaneous sarcoplasmic reticulum Ca
      release. Reduction of I(K1) by low [K(+)](o) strongly promotes ventricular
      arrhythmias mediated by phase 3 EADs in acquired long-QT syndrome caused by I(Kr)
      blockade.

PMID- 21078814
TI  - Delusional disorders--are they simply paranoid schizophrenia?
AB  - OBJECTIVES: This article tries to give an answer to the question of whether
      International Classification of Diseases (ICD-10) persistent delusional disorder
      (PDD) or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV) delusional disorder (DD) is simply paranoid schizophrenia (PS). Because
      ICD-10 PDD and DSM-IV DD are identical, we use DD as a synonym. METHODS: A
      prospective and longitudinal study compared all inpatients with DD treated at the
      Halle-Wittenberg university hospital during a 14-year period with a previously
      investigated selected cohort of patients with PS. Sociodemographic data,
      symptomatology, course, and outcome parameters were examined using standardized
      instruments. The duration of the follow-up period in patients with DD was 10.8
      years and for the PS patients 12.9 years. RESULTS: Significant differences
      between DD and PS were found: DD patients are, in comparison to patients with PS,
      significantly older at onset. Less of their first-degree relatives have mental
      disorders. They less frequently come from a broken home situation. First-rank
      symptoms, relevant negative symptoms, and primary hallucinations did not occur in
      patients with DD. Patients with DD were less frequently hospitalized, and the
      duration of their hospitalization was shorter. Their outcome is much better
      regarding employment, early retirement due to the disorder, and
      psychopharmacological medication. They more often had stable heterosexual
      partnerships and were autarkic. They had lower scores in the Disability
      Assessment Scale and in Positive and Negative Syndrome Scale. The diagnosis of DD
      is very stable over time. CONCLUSIONS: The findings of this study support the
      assumption that DDs are a separate entity and only exceptionally can be a
      prodrome of schizophrenia.

PMID- 21078815
TI  - US of the intrinsic and extrinsic wrist ligaments and triangular fibrocartilage
      complex--normal anatomy and imaging technique.
AB  - Injuries of the intrinsic and extrinsic wrist ligaments can lead to chronic wrist
      pain and carpal instability, while injuries of the triangular fibrocartilage
      complex are a frequent cause of ulnar-sided wrist pain. Currently, magnetic
      resonance (MR) arthrography is the preferred imaging modality for the evaluation
      of these structures, but good results can also achieved with MR imaging without
      preceding arthrography and computed tomographic (CT) arthrography. Promising
      results have been published on ultrasonography (US) and sonoarthrography of the
      intrinsic wrist ligaments and the triangular fibrocartilage complex and on US of
      the majority of extrinsic wrist ligaments. Visualization of these structures can
      be achieved by using high-frequency linear transducers. US has the advantages of
      MR imaging and MR arthrography: lower cost, no known contraindication for
      imaging, and real-time technique with possible dynamic evaluation. This technique
      does not require imaging guided intraarticular injection of contrast medium prior
      to MR arthrography or CT arthrography and does not use ionizing radiation;
      however, US is operator dependent, which can be compensated for by using
      standardized imaging techniques. Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.e44/-/DC1.

PMID- 21078816
TI  - The essence of senescence.
AB  - Almost half a century after the first reports describing the limited replicative
      potential of primary cells in culture, there is now overwhelming evidence for the
      existence of "cellular senescence" in vivo. It is being recognized as a critical
      feature of mammalian cells to suppress tumorigenesis, acting alongside cell death
      programs. Here, we review the various features of cellular senescence and discuss
      their contribution to tumor suppression. Additionally, we highlight the power and
      limitations of the biomarkers currently used to identify senescent cells in vitro
      and in vivo.

PMID- 21078817
TI  - Eph/ephrin molecules--a hub for signaling and endocytosis.
AB  - The development, homeostasis, and regeneration of complex organ systems require
      extensive cell-cell communication to ensure that different cells proliferate,
      migrate, differentiate, assemble, and function in a coordinated and timely
      fashion. Eph receptor tyrosine kinases and their ephrin ligands are critical
      regulators of cell contact-dependent signaling and patterning. Eph/ephrin binding
      can lead to very diverse biological readouts such as adhesion versus repulsion,
      or increased versus decreased motility. Accordingly, depending on cell type and
      context, a limited and conserved set of receptor-ligand interactions is
      translated into a large variety of downstream signaling processes. Recent
      evidence indicates that the endocytosis of Eph/ephrin molecules, together with
      the internalization of various associated tissue-specific effectors, might be one
      of the key principles responsible for such highly diverse and adaptable
      biological roles. Here, we summarize recent insights into Eph/ephrin signaling
      and endocytosis in three biological systems; i.e., the brain, intestine, and
      vasculature.

PMID- 21078818
TI  - Canonical and noncanonical Wnts use a common mechanism to activate completely
      unrelated coreceptors.
AB  - Wnt ligands signal through beta-catenin and are critically involved in cell fate
      determination and stem/progenitor self-renewal. Wnts also signal through beta
      catenin-independent or noncanonical pathways that regulate crucial events during
      embryonic development. The mechanism of noncanonical receptor activation and how
      Wnts trigger canonical as opposed to noncanonical signaling have yet to be
      elucidated. We demonstrate here that prototype canonical Wnt3a and noncanonical
      Wnt5a ligands specifically trigger completely unrelated endogenous coreceptors
      LRP5/6 and Ror1/2, respectively-through a common mechanism that involves their
      Wnt-dependent coupling to the Frizzled (Fzd) coreceptor and recruitment of shared
      components, including dishevelled (Dvl), axin, and glycogen synthase kinase 3
      (GSK3). We identify Ror2 Ser 864 as a critical residue phosphorylated by GSK3 and
      required for noncanonical receptor activation by Wnt5a, analogous to the priming
      phosphorylation of low-density receptor-related protein 6 (LRP6) in response to
      Wnt3a. Furthermore, this mechanism is independent of Ror2 receptor Tyr kinase
      functions. Consistent with this model of Wnt receptor activation, we provide
      evidence that canonical and noncanonical Wnts exert reciprocal pathway inhibition
      at the cell surface by competition for Fzd binding. Thus, different Wnts, through
      their specific coupling and phosphorylation of unrelated coreceptors, activate
      completely distinct signaling pathways.

PMID- 21078819
TI  - Crystal structure of TtgV in complex with its DNA operator reveals a general
      model for cooperative DNA binding of tetrameric gene regulators.
AB  - The majority of bacterial gene regulators bind as symmetric dimers to palindromic
      DNA operators of 12-20 base pairs (bp). Multimeric forms of proteins, including
      tetramers, are able to recognize longer operator sequences in a cooperative
      manner, although how this is achieved is not well understood due to the lack of
      complete structural information. Models, instead of structures, of complete
      tetrameric assembly on DNA exist in literature. Here we present the crystal
      structures of the multidrug-binding protein TtgV, a gene repressor that controls
      efflux pumps, alone and in complex with a 42-bp DNA operator containing two TtgV
      recognition sites at 2.9 A and 3.4 A resolution. These structures represent the
      first full-length functional tetrameric protein in complex with its intact DNA
      operator containing two continuous recognition sites. TtgV binds to its DNA
      operator as a highly asymmetric tetramer and induces considerable distortions in
      the DNA, resulting in a 60 degrees  bend. Upon binding to its operator, TtgV
      undergoes large conformational changes at the monomeric, dimeric, and tetrameric
      levels. The structures here reveal a general model for cooperative DNA binding of
      tetrameric gene regulators and provide a structural basis for a large body of
      biochemical data and a reinterpretation of previous models for tetrameric gene
      regulators derived from partial structural data.

PMID- 21078822
TI  - The Norwegian EUROPEP questionnaire for patient evaluation of general practice:
      data quality, reliability and construct validity.
AB  - BACKGROUND: The EUROPEP is a widely used international instrument to evaluate
      general practice care from the perspective of patients, but measurement
      properties including reliability at the GP level are not sufficiently documented.
      OBJECTIVE: The objectives of this study were to assess the psychometric
      properties of the Norwegian version of the EUROPEP and estimate GP-level
      reliability for scales and items. METHODS: Nine hundred patients consulting nine
      GPs at a medical centre in Norway were invited to complete the Norwegian EUROPEP
      at home following a recent consultation. We assessed item missing and ceiling
      effects and used factor analysis to assess the structure of the 23 items of the
      EUROPEP. Scales were tested for reliability and construct validity, while
      reliability at the GP level was tested for items and scales. RESULTS: Five
      hundred and fifty-seven patients (61.9%) returned the questionnaire. Seven of 23
      items had missing responses >10% and 20% had high ceiling effects. Factor
      analysis identified two groups of questions that formed scales with satisfactory
      internal consistency reliability and validity. The clinical behaviour scale (12
      items) and the organization of care scale (4 items) met the criterion of 0.7 for
      Cronbach's alpha. The GP-level reliability was >0.7 for both scales, but 9 of 23
      items were below the criterion of 0.7. CONCLUSIONS: The study identified two
      scales in the Norwegian EUROPEP instrument with satisfactory psychometric
      properties. However, high proportions of item non-response large ceiling effects
      and low GP-level reliability for several items indicate the need for further
      instrument refinement.

PMID- 21078820
TI  - Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi.
AB  - Cosuppression is a silencing phenomenon triggered by the introduction of
      homologous DNA sequences into the genomes of organisms as diverse as plants,
      fungi, flies, and nematodes. Here we report sex-induced silencing (SIS), which is
      triggered by tandem integration of a transgene array in the human fungal pathogen
      Cryptococcus neoformans. A SXI2a-URA5 transgene array was found to be post
      transcriptionally silenced during sexual reproduction. More than half of the
      progeny that inherited the SXI2a-URA5 transgene became uracil-auxotrophic due to
      silencing of the URA5 gene. In vegetative mitotic growth, silencing of this
      transgene array occurred at an ~250-fold lower frequency, indicating that
      silencing is induced during the sexual cycle. Central components of the RNAi
      pathway-including genes encoding Argonaute, Dicer, and an RNA-dependent RNA
      polymerase-are all required for both meiotic and mitotic transgene silencing.
      URA5-derived ~22-nucleotide (nt) small RNAs accumulated in the silenced isolates,
      suggesting that SIS is mediated by RNAi via sequence-specific small RNAs. Through
      deep sequencing of the small RNA population in C. neoformans, we also identified
      abundant small RNAs mapping to repetitive transposable elements, and these small
      RNAs were absent in rdp1 mutant strains. Furthermore, a group of retrotransposons
      was highly expressed during mating of rdp1 mutant strains, and an increased
      transposition/mutation rate was detected in their progeny, indicating that the
      RNAi pathway squelches transposon activity during the sexual cycle.
      Interestingly, Ago1, Dcr1, Dcr2, and Rdp1 are translationally induced in mating
      cells, and Ago1, Dcr1, and Dcr2 localize to processing bodies (P bodies), whereas
      Rdp1 appears to be nuclear, providing mechanistic insights into the elevated
      silencing efficiency during sexual reproduction. We hypothesize that the SIS RNAi
      pathway operates to defend the genome during sexual development.

PMID- 21078823
TI  - Attitudes and child abuse reporting behaviours among Hong Kong GPs.
AB  - BACKGROUND: GPs are often the first contact for injured children and hence play a
      crucial role in early identification and intervention of child abuse cases in the
      community. OBJECTIVES: To investigate Hong Kong GPs' attitudes and behaviours
      towards child abuse reporting and their opinions on the introduction of a
      mandatory reporting system. METHODS: A cross-sectional survey was conducted in
      2006 among GPs who were attending or had attended a local postgraduate family
      medicine course. RESULTS: One hundred and seventy-one GPs participated in this
      study, among which only 8.9% received formal child abuse training. Only 35.8% of
      those GPs who had encountered suspected cases reported every case. GPs who
      considered reporting could produce more harm than good to the family or child,
      who concerned about maintaining anonymity and who were reluctant to get involved
      with legal system were less likely to make a report [odds ratio (OR) 0.21-0.27;
      95% confidence interval (CI) 0.06-0.11, 0.67-0.86]. 'Concern on own anonymity'
      was the only significant independent predictor for reporting (OR 3.47; 95% CI
      1.11-10.87). Despite the low satisfaction with the present reporting system,
      67.3% would not support the introduction of a mandatory reporting system.
      Logistic regression showed previous training could predict supportive attitude
      towards mandatory reporting (OR 4.84, 95% CI 1.01-23.27). CONCLUSIONS: This study
      shows low reporting behaviour among Hong Kong GPs. The major barriers to report
      are identified and can only be addressed by education and a carefully designed
      support system for GPs. Further research engaging a multidisciplinary approach is
      required to work towards an optimally beneficial system for the children.

PMID- 21078821
TI  - Strategies for analyzing neuronal progenitor development and neuronal migration
      in the developing cerebral cortex.
AB  - The emergence of functional neuronal connectivity in the developing cerebral
      cortex depends on 1) neural progenitor differentiation, which leads to the
      generation of appropriate number and types of neurons, and 2) neuronal migration,
      which enables the appropriate positioning of neurons so that the correct patterns
      of functional synaptic connectivity between neurons can emerge. In this review,
      we discuss 1) currently available methods to study neural progenitor development
      and differentiation in the developing cerebral cortex and emerging technologies
      in this regard, 2) assays to study the migration of descendents of progenitors
      (i.e., neurons) in vitro and in vivo, and 3) the use of these assays to probe the
      molecular control of these events in the developing brain and evaluation of gene
      functions disrupted in human neurodevelopmental disorders.

PMID- 21078825
TI  - Bleach it, switch it, bounce it, pull it: using lasers to reveal plant cell
      dynamics.

PMID- 21078824
TI  - Cellular and subcellular localization of flavin-monooxygenases involved in
      glucosinolate biosynthesis.
AB  - Glucosinolates are amino acid-derived secondary metabolites with diverse
      biological activities dependent on chemical modifications of the side chain. Five
      flavin-monooxygenases FMO(GS-OX1-5) have recently been identified as aliphatic
      glucosinolate side chain modification enzymes in Arabidopsis thaliana that
      catalyse the generation of methylsulphinylalkyl glucosinolates, which can be
      hydrolysed to products with distinctive benefits for human health and plant
      defence. Though the localization of most aliphatic glucosinolate biosynthetic
      enzymes has been determined, little is known about where the side chain
      modifications take place despite their importance. Hence, the spatial expression
      pattern of FMO(GS-OX1-5) genes in Arabidopsis was investigated by expressing
      green fluorescent protein (GFP) and beta-glucuronidase (GUS) fusion genes
      controlled by FMO(GS-OX1-5) promoters. The cellular compartmentation of FMO(GS
      OX1) was also detected by transiently expressing a FMO(GS-OX1)-yellow fluorescent
      protein (YFP) fusion protein in tobacco leaves. The results showed that FMO(GS
      OX1-5) were expressed basically in vascular tissues, especially in phloem cells,
      like other glucosinolate biosynthetic genes. They were also found in endodermis
      like cells in flower stalk and epidermal cells in leaf, which is a location that
      has not been reported for other glucosinolate biosynthetic genes. It is suggested
      that the spatial expression pattern of FMO(GS-OX1-5) determines the access of
      enzymes to their substrate and therefore affects the glucosinolate profile.
      FMO(GS-OX1)-YFP fusion protein analysis identified FMO(GS-OX1) as a cytosolic
      protein. Together with the subcellular locations of the other biosynthetic
      enzymes, an integrated map of the multicompartmentalized aliphatic glucosinolate
      biosynthetic pathway is discussed.

PMID- 21078827
TI  - How valid are the responses to nursing home survey questions? Some issues and
      concerns.
AB  - PURPOSE: Although surveys are usually piloted before fielding, cognitive-based
      testing of surveys is not standard practice in nursing home (NH) research. Many
      terms used in the literature do not have standard definitions and may be
      interpreted differently by researchers, respondents, and policy makers. The
      purpose of this study was to ensure that survey respondents understood questions
      as intended, determine whether the Nursing Home Administrator (NHA) or the
      Director of Nursing (DON) was better able to answer questions on certain topics,
      and to inform the answer choices provided for questions. METHODS: Using existing
      survey questions and input from experts, we developed surveys to be administered
      to DONs and NHAs. Cognitive-based interviews were conducted with 45 participants.
      We took detailed notes during all interviews, and 2 researchers independently
      coded these notes for key themes. RESULTS: Many terms and concepts routinely used
      by NH researchers and policy makers, such as "direct-care workers" and
      "palliative care," were not uniformly interpreted by those managing NHs. For
      example, respondents' definitions of direct-care workers ranged from nursing
      assistants to broader categories of clinical and other staff members, including
      nurses, activities staff, and social workers. We also found NHAs and DONs, at
      times, did not possess or have access to information the researchers expected
      them to. IMPLICATIONS: Our results may help explain discrepant findings across NH
      studies. They also underscore the necessity of cognitive-based testing for survey
      development and have important implications for policy decisions.

PMID- 21078826
TI  - Intermittent versus continuous chemotherapy in advanced colorectal cancer: a
      randomised 'GISCAD' trial.
AB  - BACKGROUND: In advanced colorectal cancer, chemotherapy is usually administered
      without pauses and until progression but patients can experience cumulative
      toxicity and cannot tolerate a heavy therapeutic charge. AIM: The aim of the
      present trial was to evaluate whether an intermittent chemotherapy with levo
      leucovorin + 5-fluorouracil (5-FU) + irinotecan (CPT-11) was at least as
      effective as the same regimen given continuously, both administered until
      progression, in patients affected with advanced colorectal cancer and not
      previously exposed to chemotherapy for metastatic disease. PATIENTS, MATERIALS
      AND METHODS: A total of 337 patients from 27 institutions were randomised between
      levo-leucovorin, 100/mg/m(2) i.v. + 5-FU; 400 mg/m(2) i.v. bolus + 5-FU; 600
      mg/m(2) 22-h continuous infusion, days 1 and 2 + CPT-11; 180 mg/m(2) day 1,
      administered every 2 weeks 2 months on and 2 months off (arm A) and the same
      regimen administered continuously (arm B), until progression in both arms. The
      main end point was overall survival (OS), the secondary progression-free survival
      (PFS) and toxicity. RESULTS: At a median follow-up of 41 months, OS was 18 months
      in arm A and 17 months in arm B [hazard ratio (HR), 0.88]. Also PFS was
      comparable in the two groups (6 months in both, with HR, 1.03), and even grades 3
      4 toxicity (mainly myelosuppression, fever and diarrhoea) was similar. Second
      line oxaliplatin-based treatment was administered in a similar percentage (66%)
      in the two arms. The median chemotherapy-free period (drug holiday) in arm A was
      3.5 months. CONCLUSION: Reducing the charge of therapy in this population did not
      diminish the efficacy of treatment. Further studies with this strategy, including
      biologicals, are warranted.

PMID- 21078828
TI  - The healthy worker effect in US chemical industry workers.
AB  - BACKGROUND: Occupational studies typically observe a 20% deficit in overall
      mortality, broadly characterized as the healthy worker effect (HWE). Components
      of the HWE may be addressed by various analytical approaches. AIMS: To explore
      the HWE in a modern industrial cohort. METHODS: Standardized mortality ratios
      (SMRs) were calculated for 114,683 US chemical industry employees, who worked at
      least 3 days between 1960 and 2005. RESULTS: SMRs were 79 (95% confidence
      interval 78-80) for all causes, 81 (95% confidence interval 79-82) for heart
      disease, 70 (95% confidence interval 67-73) for non-malignant respiratory
      disease, 83 (95% confidence interval 81-85) for smoking-related cancers (buccal,
      cervix, oesophagus, stomach, pancreas, lung, larynx, bladder and kidney) combined
      and 97 (95% confidence interval 95-100) for other cancers. CONCLUSIONS: The low
      SMRs observed in this study are likely due to differential smoking between the
      cohort and the background population. Future considerations to control for the
      HWE should take this into account.

PMID- 21078829
TI  - Upper respiratory impairment in restorers of cultural heritage.
AB  - BACKGROUND: There is a paucity of data regarding respiratory health in restorers
      of cultural heritage or similar occupations, such as visual artists or museum
      workers, although they are exposed to a complex mixture of various respiratory
      hazards. AIMS: To evaluate atopy and respiratory health parameters, including
      bronchial and nasal non-specific reactivity, in restorers and conservators of
      cultural heritage (restorers). METHODS: Fifty-six restorers and 62 controls
      provided general data and data on ever experienced rhinitic or asthma-like
      symptoms, spirometry, non-specific bronchial and nasal responsiveness to
      histamine, skin prick testing to common inhalational allergens and serum total
      IgE levels. RESULTS: Spirometry values were in the range of normal values in 55
      of 56 restorers and did not differ significantly from those in control subjects.
      However, restorers had more than two times higher prevalence of nasal hyper
      responsiveness (NHR), with 2.3 times higher risk of NHR compared to controls [95%
      confidence interval (CI): 1.4-3.6, P < 0.001]. The risk of NHR was slightly
      reduced by increasing age (odds ratio 0.95, 95% CI: 0.91-0.99, P < 0.05). NHR was
      not associated with gender, smoking status, bronchial hyperresponsiveness (BHR),
      upper or lower respiratory symptoms or atopy status. CONCLUSIONS: Compared with
      controls, the studied group of workers occupationally exposed to respiratory
      hazards during restoration/conservation activities had no deterioration of lung
      function but had an increased non-specific nasal responsiveness that was not
      correlated with upper and lower respiratory symptoms, BHR or atopy. The
      relationship of this finding to future clinical outcome should be investigated in
      a longitudinal study.

PMID- 21078830
TI  - Work-related accidents and daylight saving time in Finland.
AB  - BACKGROUND: Recent research has indicated that transitions into and out of
      daylight saving time (DST) unbalance the physiological circadian rhythm and may
      lead to sleep disturbance. Sleep deprivation may have negative effects on
      motivation, attention and alertness and thus it is possible that transitions into
      and out of DST may increase accident rates. AIMS: To explore the impact of DST
      transitions on the number of occupational accidents in Finland. METHODS: For the
      study, we analysed all occupational accidents that happened in Finland 1 week
      before and 1 week after DST transitions during the years 2002-06. RESULTS:
      Transitions into and out of DST did not significantly increase the number of
      occupational accidents. CONCLUSIONS: It seems that sleep deprivation after DST
      transition is not harmful enough to impact on occupational accident rates.

PMID- 21078831
TI  - Dipstick tests for cotinine: comment on the article by Best et al.

PMID- 21078832
TI  - Smoking cessation advantage among adult initiators: does it apply to black women?
AB  - INTRODUCTION: Smokers who initiate as adults are more likely to quit than those
      who initiate as adolescents. Black women are more likely than White women to
      initiate smoking in adulthood and are less likely to quit. There is a paucity of
      research examining whether the smoking cessation advantage among adult initiators
      applies to Black women. The study objective is to examine race differences in the
      effect of developmental stage of smoking initiation on number of years until
      cessation among Black and White women. METHODS: Data were extracted from the
      National Longitudinal Survey of Young Women, a national cohort of women between
      the ages of 49 and 61 years in 2003. The analytic sample comprised 1,008 White
      women and 271 Black women with a history of smoking. Survival analysis procedures
      were utilized to address the study objective. RESULTS: Racial disparities in
      smoking cessation were most evident among women who initiated smoking as adults.
      White young adult initiators had a 31% increased hazard of smoking cessation
      advantage (adjusted hazards ratio [HR]: 1.31, 95% CI: 1.04-1.65) over adolescent
      initiators, whereas Black young adult initiators had no smoking cessation
      advantage (adjusted HR: 0.85, CI: 95% 0.55-1.30) over adolescent initiators.
      CONCLUSIONS: Prior observations that smoking initiation in adulthood is
      associated with high rates of cessation do not apply to black women. To
      contribute to the reduction of disparities in women's cessation efforts to
      prevent initiation should target young adult women, particularly Black young
      adult women.

PMID- 21078834
TI  - The echocardiographic assessment of functional mitral regurgitation.
AB  - Functional mitral regurgitation (MR) is common, clinically important, and
      mechanistically complex. Its assessment by echocardiography can be challenging,
      and particular care is needed in the quantification of severity.
      Echocardiographers need to be aware of the potential limitations of flow
      convergence and vena contracta methods in assessing severity and alert to the
      prognostic importance of even moderate functional MR. Three-dimensional
      echocardiography has the potential to improve both the understanding of the
      mechanisms of functional MR and the accuracy of its quantification.

PMID- 21078835
TI  - Three-dimensional imaging of the atrial septum and patent foramen ovale anatomy:
      defining the morphological phenotypes of patent foramen ovale.
AB  - Patent foramen ovale (PFO) is known to occur with greater prevalence in those
      with cryptogenic stroke. These observations support the role of a PFO as a
      channel for paradoxical embolism and a mechanism for cerebral ischaemic events.
      Transcatheter closure of PFO may be indicated in this setting. A prerequisite of
      procedural success is achieving complete closure of the shunt. Studies have shown
      a varying degree of successful shunt closure. Residual shunts are usually the
      result of a mismatch between the device shape and PFO anatomy. In this article,
      we review the features of PFO and their surrounding structures as seen by three
      dimensional transoesophageal echocardiography in patients undergoing
      transcatheter closure and relate these to the variations in morphology on
      anatomical specimens for a better appreciation of their suitability for closure
      devices. The salient features of the anatomical variations seen in adults
      undergoing transcatheter device closure have been summarized and used to produce
      a practical pre-procedural checklist.

PMID- 21078836
TI  - The role of echocardiography in diagnosis, monitoring closure and post-procedural
      assessment of patent foramen ovale.
AB  - Patent foramen ovale (PFO) is common, with a probe-patent PFO present in 15-35%
      of the general population. Patent foramen ovale has been implicated in the
      aetiology of a number of different pathologies, including cryptogenic stroke,
      decompression sickness in divers, platypnea orthodeoxia, and migraine with aura.
      Cardiac ultrasound has a major role not only in the diagnosis of PFO but also in
      monitoring subsequent therapeutic intervention and in the post-procedural
      assessment of patients following percutaneous closure. The aim of this review was
      to outline the data regarding the role of echocardiography in diagnosis, during
      monitoring and post-procedural assessment so as to provide practical advice to
      minimize error and optimize patient outcomes. The review will seek to outline the
      limitations of the available techniques and factors that should be taken into
      account during percutaneous device closure.

PMID- 21078837
TI  - Anatomy of the mitral valve: understanding the mitral valve complex in mitral
      regurgitation.
AB  - Imaging the mitral valve requires an understanding of the normal anatomy and how
      this complex structure is altered by disease states. Mitral regurgitation is
      increasingly prevalent. Despite the fall in rheumatic disease, it is the second
      most common valvular lesion seen in adults in Europe. In this review, the
      morphology of the normal and abnormal valve is reconsidered in relation to the
      key structures, with a view to aiding the reader in understanding how this might
      relate to echocardiographic identification of abnormalities.

PMID- 21078838
TI  - Phospholipidation of HDL--how much is too much?

PMID- 21078839
TI  - Determining decision limits for new biomarkers: clinical and statistical
      considerations.

PMID- 21078840
TI  - Targeted massively parallel sequencing of maternal plasma DNA permits efficient
      and unbiased detection of fetal alleles.
AB  - BACKGROUND: Massively parallel sequencing has recently been used in noninvasive
      prenatal diagnosis. The current costs of this technology are still relatively
      expensive, however, and sample throughput is still relatively low when it is used
      as a molecular diagnostic tool. Rather than nonselectively sequencing the genome,
      target enrichment provides a logical approach for more efficient and cost
      effective massively parallel sequencing because it increases the proportion of
      informative data from the targeted region(s). Existing applications of targeted
      sequencing have mainly been qualitative analyses of genomic DNA. In this study,
      we investigated its applicability in enriching selected genomic regions from
      plasma DNA and the quantitative performance of this approach. METHODS: DNA was
      extracted from plasma samples collected from 12 pregnant women carrying female
      fetuses. The SureSelect Target Enrichment System (Agilent Technologies) was used
      to enrich for exons on chromosome X. Plasma DNA libraries with and without target
      enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of
      the mother and fetus for each case were genotyped by microarray. RESULTS: For the
      regions targeted by the enrichment kit, the mean sequence coverage of the
      enriched samples was 213-fold higher than that of the nonenriched samples.
      Maternal and fetal DNA molecules were enriched evenly. After target enrichment,
      the coverage of fetus-specific alleles within the targeted region increased from
      3.5% to 95.9%. CONCLUSIONS: Targeted sequencing of maternal plasma DNA permits
      efficient and unbiased detection of fetal alleles at genomic regions of interest
      and is a powerful method for measuring the proportion of fetal DNA in a maternal
      plasma sample.

PMID- 21078841
TI  - Plasma cannabinoid pharmacokinetics following controlled oral delta9
      tetrahydrocannabinol and oromucosal cannabis extract administration.
AB  - BACKGROUND: Sativex((r)), a cannabis extract oromucosal spray containing Delta(9)
      tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III
      trials as an adjunct to opioids for cancer pain treatment, and recently received
      United Kingdom approval for treatment of spasticity. There are indications that
      CBD modulates THC's effects, but it is unclear if this is due to a
      pharmacokinetic and/or pharmacodynamic interaction. METHODS: Cannabis smokers
      provided written informed consent to participate in this randomized, controlled,
      double-blind, double-dummy institutional review board-approved study.
      Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and
      5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over
      5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified
      in plasma by 2-dimensional GC-MS. Lower limits of quantification were <=0.25
      MUg/L. RESULTS: Nine cannabis smokers completed all 5 dosing sessions.
      Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and
      areas under the curve from 0-10.5 h postdose (AUC(0->10.5)) for all analytes were
      found between low and high doses of synthetic THC and Sativex. There were no
      statistically significant differences in C(max), time to maximum concentration or
      in the AUC(0->10.5) between similar oral THC and Sativex doses. Relative
      bioavailability was calculated to determine the relative rate and extent of THC
      absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8%
      (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION: These data
      suggest that CBD modulation of THC's effects is not due to a pharmacokinetic
      interaction at these therapeutic doses.

PMID- 21078842
TI  - The impact of school-located influenza vaccination programs on student
      absenteeism: a review of the U.S. literature.
AB  - A literature review was conducted to summarize the impact of school-located
      influenza vaccination (SLIV) programs on school absenteeism. Seven studies were
      identified: six peer-reviewed articles and one conference presentation. The
      number of students vaccinated ranged from 185 to 5,315, representing 35-86% of
      enrolled students. Six studies compared absenteeism for students in SLIV schools
      and control schools; all found absenteeism decreased in SLIV schools. Three
      studies compared absenteeism for vaccinated and unvaccinated students in SLIV
      schools; all found that absenteeism was reduced for vaccinated students. Benefits
      were also reported to extend beyond the vaccinated children; one study found that
      absenteeism was significantly reduced among high school students when elementary
      school students were vaccinated. The available evidence indicates that SLIV
      programs reduce student absenteeism during the influenza season. Additional
      research into sustainable funding sources and the comprehensive effects of SLIV
      programs on students, families, staff, and the community is warranted.

PMID- 21078843
TI  - Understanding the context of providing HIV prevention and treatment in Papua New
      Guinea.
AB  - The HIV epidemic in Papua New Guinea is now described as a generalized epidemic;
      that is, more than 1% of people aged 15 to 49 years are infected with HIV. The
      individual behavior of people is not the single most important factor that places
      them at risk of infection and drives the spread of the epidemic. Rather, a
      diverse range of factors-biological, sociocultural, and political-makes people
      vulnerable to infection and dictates their access to care and treatment services.
      This article examines these biological, sociocultural, and political influences
      on the HIV epidemic and on prevention and treatment strategies in Papua New
      Guinea.

PMID- 21078844
TI  - Vaccination against Chlamydia genital infection utilizing the murine C. muridarum
      model.
AB  - Chlamydia trachomatis genital infection is a worldwide public health problem, and
      considerable effort has been expended on developing an efficacious vaccine. The
      murine model of C. muridarum genital infection has been extremely useful for
      identification of protective immune responses and in vaccine development.
      Although a number of immunogenic antigens have been assessed for their ability to
      induce protection, the majority of studies have utilized the whole organism, the
      major outer membrane protein (MOMP), or the chlamydial protease-like activity
      factor (CPAF). These antigens, alone and in combination with a variety of
      immunostimulatory adjuvants, have induced various levels of protection against
      infectious challenge, ranging from minimal to nearly sterilizing immunity.
      Understanding of the mechanisms of natural infection-based immunity and advances
      in adjuvant biology have resulted in studies that are increasingly successful,
      but a vaccine licensed for use in humans has not yet been brought to fruition.
      Here we review immunity to chlamydial genital infection and vaccine development
      using the C. muridarum model.

PMID- 21078845
TI  - Antibody to receptor activator of NF-kappaB ligand ameliorates T cell-mediated
      periodontal bone resorption.
AB  - Activated T and B lymphocytes in periodontal disease lesions express receptor
      activator of NF-kappaB ligand (RANKL), which induces osteoclastic bone
      resorption. The objective of this study was to evaluate the effects of anti-RANKL
      antibody on periodontal bone resorption in vitro and in vivo. Aggregatibacter
      actinomycetemcomitans outer membrane protein 29 (Omp29) and A.
      actinomycetemcomitans lipopolysaccharide (LPS) were injected into 3 palatal
      gingival sites, and Omp29-specific T clone cells were transferred into the tail
      veins of rats. Rabbit anti-RANKL IgG antibody or F(ab')2 antibody fragments
      thereof were injected into the palatal sites in each rat (days -1, 1, and 3).
      Anti-RANKL IgG antibody significantly inhibited soluble RANKL (sRANKL)-induced
      osteoclastogenesis in vitro, in a dose-dependent manner, but also gave rise to a
      rat antibody response to rabbit IgG in vivo, with no significant inhibition of
      periodontal bone resorption detected. Lower doses (1.5 and 0.15 MUg/3 sites) of
      F(ab')2 antibody were not immunogenic in the context of the experimental model.
      Periodontal bone resorption was inhibited significantly by injection of the anti
      RANKL F(ab')2 antibody into gingivae. The sRANKL concentrations for the antibody
      treated groups were decreased significantly compared to those for the untreated
      group. Osteoclasts on the alveolar bone surface were also diminished
      significantly after antibody injection. Gingival sRANKL concentration and bone
      loss showed a significant correlation with one another in animals receiving anti
      RANKL F(ab')2 antibody. These results suggest that antibody to RANKL can inhibit
      A. actinomycetemcomitans-specific T cell-induced periodontal bone resorption by
      blockade and reduction of tissue sRANKL, providing an immunological approach to
      ameliorate immune cell-mediated periodontal bone resorption.

PMID- 21078846
TI  - Uropathogenic Escherichia coli induces chronic pelvic pain.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating
      syndrome of unknown etiology often postulated, but not proven, to be associated
      with microbial infection of the prostate gland. We hypothesized that infection of
      the prostate by clinically relevant uropathogenic Escherichia coli (UPEC) can
      initiate and establish chronic pain. We utilized an E. coli strain newly isolated
      from a patient with CP/CPPS (strain CP1) and examined its molecular pathogenesis
      in cell culture and in a murine model of bacterial prostatitis. We found that CP1
      is an atypical isolate distinct from most UPEC in its phylotype and virulence
      factor profile. CP1 adhered to, invaded, and proliferated within prostate
      epithelia and colonized the prostate and bladder of NOD and C57BL/6J mice. Using
      behavioral measures of pelvic pain, we showed that CP1 induced and sustained
      chronic pelvic pain in NOD mice, an attribute not exhibited by a clinical
      cystitis strain. Furthermore, pain was observed to persist even after bacterial
      clearance from genitourinary tissues. CP1 induced pelvic pain behavior
      exclusively in NOD mice and not in C57BL/6J mice, despite comparable levels of
      colonization and inflammation. Microbial infections can thus serve as initiating
      agents for chronic pelvic pain through mechanisms that are dependent on both the
      virulence of the bacterial strain and the genetic background of the host.

PMID- 21078847
TI  - Downregulation of GbpB, a component of the VicRK regulon, affects biofilm
      formation and cell surface characteristics of Streptococcus mutans.
AB  - The virulence of the dental caries pathogen Streptococcus mutans relies in part
      on the sucrose-dependent synthesis of and interaction with glucan, a major
      component of the extracellular matrix of tooth biofilms. However, the mechanisms
      by which secreted and/or cell-associated glucan-binding proteins (Gbps) produced
      by S. mutans participate in biofilm growth remain to be elucidated. In this
      study, we further investigate GbpB, an essential immunodominant protein with
      similarity to murein hydrolases. A conditional knockdown mutant that expressed
      gbpB antisense RNA under the control of a tetracycline-inducible promoter was
      constructed in strain UA159 (UACA2) and used to investigate the effects of GbpB
      depletion on biofilm formation and cell surface-associated characteristics.
      Additionally, regulation of gbpB by the two-component system VicRK was
      investigated, and phenotypic analysis of a vicK mutant (UAvicK) was performed.
      GbpB was directly regulated by VicR, and several phenotypic changes were
      comparable between UACA2 and UAvicK, although differences between these strains
      existed. It was established that GbpB depletion impaired initial phases of
      sucrose-dependent biofilm formation, while exogenous native GbpB partially
      restored the biofilm phenotype. Several cellular traits were significantly
      affected by GbpB depletion, including altered cell shape, decreased autolysis,
      increased cell hydrophobicity, and sensitivity to antibiotics and osmotic and
      oxidative stresses. These data provide the first experimental evidence for GbpB
      participation in sucrose-dependent biofilm formation and in cell surface
      properties.

PMID- 21078848
TI  - Host and pathogen glycosaminoglycan-binding proteins modulate antimicrobial
      peptide responses in Drosophila melanogaster.
AB  - During group B streptococcal infection, the alpha C protein (ACP) on the
      bacterial surface binds to host cell surface heparan sulfate proteoglycans
      (HSPGs) and facilitates entry of bacteria into human epithelial cells. Previous
      studies in a Drosophila melanogaster model showed that binding of ACP to the
      sulfated polysaccharide chains (glycosaminoglycans) of HSPGs promotes host death
      and is associated with higher bacterial burdens. We hypothesized that ACP
      glycosaminoglycan binding might determine infection outcome by altering host
      responses to infection, such as expression of antimicrobial peptides. As
      glycosaminoglycans/HSPGs also interact with a number of endogenous secreted
      signaling molecules in Drosophila, we examined the effects of host and pathogen
      glycosaminoglycan/HSPG-binding structures in host survival of infection and
      antimicrobial peptide expression. Strikingly, host survival after infection with
      wild-type streptococci was enhanced among flies overexpressing the endogenous
      glycosaminoglycan/HSPG-binding morphogen Decapentaplegic-a transforming growth
      factor beta-like Drosophila homolog of mammalian bone morphogenetic proteins-but
      not by flies overexpressing a mutant, non-glycosaminoglycan-binding
      Decapentaplegic, or the other endogenous glycosaminoglycan/HSPG-binding
      morphogens, Hedgehog and Wingless. While ACP-glycosaminoglycan binding was
      associated with enhanced transcription of peptidoglycan recognition proteins and
      antimicrobial peptides, Decapentaplegic overexpression suppressed transcription
      of these genes during streptococcal infection. Further, the glycosaminoglycan
      binding domain of ACP competed with Decapentaplegic for binding to the soluble
      glycosaminoglycan heparin in an in vitro assay. These data suggest that, in
      addition to promoting bacterial entry into host cells, ACP competes with
      Decapentaplegic for binding to glycosaminoglycans/HSPGs during infection and that
      these bacterial and endogenous glycosaminoglycan-binding structures determine
      host survival and regulate antimicrobial peptide transcription.

PMID- 21078849
TI  - Granuloma formation around filarial larvae triggered by host responses to an
      excretory/secretory antigen.
AB  - In previous studies using a murine model of filarial infection, granuloma
      formation was found to be a most important host-protective mechanism. We have
      also shown that in vitro cytoadherence is a surrogate for the formation of
      antifilarial granulomas in vivo and that it requires "alternatively activated"
      host cells and a source of antifilarial antibody. We show here that antibodies
      against L3 excretory/secretory (E/S) products can facilitate in vitro
      cytoadherence. We generated a set of hybridomas reactive with filarial E/S
      products and screened them for their ability to mediate in vitro cytoadherence.
      One clone (no. 1E9) was positive in this assay. We then screened a novel
      expression library of filarial antigens displayed on the surface of T7
      bacteriophage for reactivity with 1E9. Phage expressing two filarial antigens
      (TCTP and BmALT-2) reacted with 1E9. Immunization of mice showed that the cohort
      immunized with BmALT-2 cleared a challenge infection with infective Brugia
      pahangi L3 in an accelerated manner, whereas cohorts immunized with TCTP cleared
      larvae with the same kinetics as in unimmunized mice. These data confirm that
      BmALT-2 is the antigenic target of granuloma-mediated killing of B. pahangi L3.
      Our findings also confirm previous studies that BmALT-2 is a potential vaccine
      candidate for filarial infection. Our data reinforce the work of others and also
      provide a possible mechanism by which immune responses to BmALT-2 may provide
      host protection.

PMID- 21078850
TI  - Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent
      mechanisms.
AB  - Invasive aspergillosis is a major threat for patients suffering from chronic
      granulomatous disease (CGD). Although Aspergillus fumigatus is the most commonly
      encountered Aspergillus species, the presence of A. nidulans appears to be
      disproportionately high in CGD patients. The purpose of this study was to
      investigate the involvement of the NADPH oxidase and the resulting reactive
      oxygen species (ROS) in host defense against fungi and to clarify their
      relationship toward A. nidulans. Murine CGD alveolar macrophages (AM) and
      polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells (PBMC)
      from healthy controls and CGD patients were challenged with either A. fumigatus
      or A. nidulans. Analysis of the antifungal effects of ROS revealed that A.
      nidulans, in contrast to A. fumigatus, is not susceptible to ROS. In addition,
      infection with live A. nidulans did not result in any measurable ROS release.
      Remarkably, human CGD PMN and PBMC and murine CGD AM were at least equipotent at
      arresting conidial germination compared to healthy controls. Blocking of the
      NADPH oxidase resulted in significantly reduced damage of A. fumigatus but did
      not affect A. nidulans hyphae. Furthermore, the microbicidal activity of CGD PMN
      was maintained toward A. nidulans but not A. fumigatus. In summary, antifungal
      resistance to A. nidulans is not directly ROS related. The etiology of A.
      nidulans infections in CGD cannot be explained by the simple absence of the
      direct microbicidal effect of ROS. In vivo, the NADPH oxidase is a critical
      regulator of innate immunity whose unraveling will improve our understanding of
      fungal pathogenesis in CGD.

PMID- 21078851
TI  - Proinflammatory cytokine gene expression in the stomach correlates with vaccine
      induced protection against Helicobacter pylori infection in mice: an important
      role for interleukin-17 during the effector phase.
AB  - CD4(+) T cells have been shown to be essential for vaccine-induced protection
      against Helicobacter pylori infection in mice. Less is known about the relative
      contributions of individual cell subpopulations, such as T(h)1 and T(h)17 cells,
      and their associated cytokines. The aim of the present study was to find immune
      correlates to vaccine-induced protection and further study their role in
      protection against H. pylori infection. Immunized and unimmunized mice were
      challenged with H. pylori, and immune responses were compared. Vaccine-induced
      protection was assessed by measuring H. pylori colonization in the stomach.
      Gastric gene expression of T(h)1- and/or T(h)17-associated cytokines was analyzed
      by quantitative PCR, and contributions of individual cytokines to protection were
      evaluated by antibody-mediated in vivo neutralization. By analyzing immunized and
      unimmunized mice, a significant inverse correlation between the levels of
      interleukin-12p40 (IL-12p40), tumor necrosis factor alpha (TNF), gamma interferon
      (IFN-gamma), and IL-17 gene expression and the number of H. pylori bacteria in
      the stomachs of individual animals after challenge could be demonstrated. In a
      kinetic study, upregulation of TNF, IFN-gamma, and IL-17 coincided with vaccine
      induced protection at 7 days after H. pylori challenge and was sustained for at
      least 21 days. In vivo neutralization of these cytokines during the effector
      phase of the immune response revealed a significant role for IL-17, but not for
      IFN-gamma or TNF, in vaccine-induced protection. In conclusion, although both
      T(h)1- and T(h)17-associated gene expression in the stomach correlate with
      vaccine-induced protection against H. pylori infection, our study indicates that
      mainly T(h)17 effector mechanisms are of critical importance to protection.

PMID- 21078852
TI  - Mycobacterium tuberculosis lipoproteins directly regulate human memory CD4(+) T
      cell activation via Toll-like receptors 1 and 2.
AB  - The success of Mycobacterium tuberculosis as a pathogen relies on its ability to
      regulate the host immune response. M. tuberculosis can manipulate adaptive T cell
      responses indirectly by modulating antigen-presenting cell (APC) function or by
      directly interacting with T cells. Little is known about the role of M.
      tuberculosis molecules in direct regulation of T cell function. Using a
      biochemical approach, we identified lipoproteins LprG and LpqH as major molecules
      in M. tuberculosis lysate responsible for costimulation of primary human CD4(+) T
      cells. In the absence of APCs, activation of memory CD4(+) T cells with LprG or
      LpqH in combination with anti-CD3 antibody induces Th1 cytokine secretion and
      cellular proliferation. Lipoprotein-induced T cell costimulation was inhibited by
      blocking antibodies to Toll-like receptor 2 (TLR2) and TLR1, indicating that
      human CD4(+) T cells can use TLR2/TLR1 heterodimers to directly respond to M.
      tuberculosis products. M. tuberculosis lipoproteins induced NF-kappaB activation
      in CD4(+) T cells in the absence of TCR co-engagement. Thus, TLR2/TLR1 engagement
      alone by M. tuberculosis lipoprotein triggered intracellular signaling, but
      upregulation of cytokine production and proliferation required co-engagement of
      the TCR. In conclusion, our results demonstrate that M. tuberculosis lipoproteins
      LprG and LpqH participate in the regulation of adaptive immunity not only by
      inducing cytokine secretion and costimulatory molecules in innate immune cells
      but also through directly regulating the activation of memory T lymphocytes.

PMID- 21078853
TI  - Characterization of avian gammadelta T-cell subsets after Salmonella enterica
      serovar Typhimurium infection of chicks.
AB  - Avian gammadelta T lymphocytes are frequently found in blood and organs and are
      assumed to be crucial to the immune defense against Salmonella infections of
      chicks. To elucidate the so-far-unknown immunological features of subpopulations
      of avian gammadelta T cells in the course of infection, day-old chicks were
      infected orally with Salmonella enterica serovar Typhimurium. Until 11 days after
      infection, the occurrence as well as transcription of the CD8 antigen and
      immunologically relevant protein genes of CD8alpha(-) and CD8alpha(+high)
      (CD8alphaalpha(+) CD8alphabeta(+)) gammadelta cells were analyzed using flow
      cytometry and quantitative real-time reverse transcription-PCR (RT-PCR) with
      blood, spleen, thymus, and cecum samples. After infection, an increased
      percentage of CD8alpha(+high) gammadelta T lymphocytes was found in blood, in
      spleen, and, with the highest values and most rapidly, in cecum. Within the
      CD8alpha(+high) subset, a significant rise in the number of CD8alphaalpha(+)
      cells was accompanied by enhanced CD8alpha antigen expression and reduced gene
      transcription of the CD8beta chain. CD8alphaalpha(+) and CD8alphabeta(+) cells
      showed elevated transcription for Fas, Fas ligand (FasL), interleukin-2 receptor
      alpha (IL-2Ralpha), and gamma interferon (IFN-gamma). While the highest fold
      changes in mRNA levels were observed in CD8alphabeta(+) cells, the mRNA
      expression rates of CD8alphabeta(+) cells never significantly exceeded those of
      the CD8alphaalpha(+) cells. In conclusion, both CD8alpha(+high) gammadelta T-cell
      subpopulations (CD8alphaalpha(+) and CD8alphabeta(+)) might be a potential source
      of IFN-gamma in Salmonella-infected chicks. However, due to their prominent
      frequency in blood and organs after infection, the avian CD8alphaalpha(+)
      gammadelta T-cell subset seems to be unique and of importance in the course of
      Salmonella Typhimurium infection of very young chicks.

PMID- 21078855
TI  - Impact of glutamine transporters on pneumococcal fitness under infection-related
      conditions.
AB  - The genomic analysis of Streptococcus pneumoniae predicted six putative glutamine
      uptake systems, which are expressed under in vitro conditions, as shown here by
      reverse transcription-PCR. Four of these operons consist of glnHPQ, while two
      lack glnH, which encodes a soluble glutamine-binding protein. Here, we studied
      the impact of two of these glutamine ATP-binding cassette transporters on S.
      pneumoniae D39 virulence and phagocytosis, which consist of GlnQ and a
      translationally fused protein of GlnH and GlnP. Mice infected intranasally with
      D39Deltagln0411/0412 showed significantly increased survival times and a
      significant delay in the development of pneumococcal pneumonia compared to those
      infected with D39, as observed in real time using bioluminescent pneumococci. In
      a mouse sepsis model, the mutant D39Deltagln0411/0412 showed only moderate but
      significant attenuation. In contrast, the D39Deltagln1098/1099 knockout strain
      was massively attenuated in the pneumonia and septicemia mouse infection model.
      To cause pneumonia or sepsis with D39Deltagln1098/1099, infection doses 100- to
      10,000-fold higher than those used for wild-type strain D39 were required. In an
      experimental mouse meningitis model, D39Deltagln1098/1099 produced decreased
      levels of white blood cells in cerebrospinal fluid and showed decreased numbers
      of bacteria in the bloodstream compared to D39 and D39Deltagln0411/0412.
      Phagocytosis experiments revealed significantly decreased intracellular survival
      rates of mutants D39Deltagln1098/1099 and D39Deltagln0411/0412 compared to wild
      type D39, suggesting that the deficiency of Gln uptake systems impairs resistance
      to oxidative stress. Taken together, our results demonstrate that both glutamine
      uptake systems are required for full virulence of pneumococci but exhibit
      different impacts on the pathogenesis of pneumococci under in vivo conditions.

PMID- 21078854
TI  - A comparative genomic analysis of diverse clonal types of enterotoxigenic
      Escherichia coli reveals pathovar-specific conservation.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal illness in
      children less than 5 years of age in low- and middle-income nations, whereas it
      is an emerging enteric pathogen in industrialized nations. Despite being an
      important cause of diarrhea, little is known about the genomic composition of
      ETEC. To address this, we sequenced the genomes of five ETEC isolates obtained
      from children in Guinea-Bissau with diarrhea. These five isolates represent
      distinct and globally dominant ETEC clonal groups. Comparative genomic analyses
      utilizing a gene-independent whole-genome alignment method demonstrated that
      sequenced ETEC strains share approximately 2.7 million bases of genomic sequence.
      Phylogenetic analysis of this "core genome" confirmed the diverse history of the
      ETEC pathovar and provides a finer resolution of the E. coli relationships than
      multilocus sequence typing. No identified genomic regions were conserved
      exclusively in all ETEC genomes; however, we identified more genomic content
      conserved among ETEC genomes than among non-ETEC E. coli genomes, suggesting that
      ETEC isolates share a genomic core. Comparisons of known virulence and of surface
      exposed and colonization factor genes across all sequenced ETEC genomes not only
      identified variability but also indicated that some antigens are restricted to
      the ETEC pathovar. Overall, the generation of these five genome sequences, in
      addition to the two previously generated ETEC genomes, highlights the genomic
      diversity of ETEC. These studies increase our understanding of ETEC evolution, as
      well as provide insight into virulence factors and conserved proteins, which may
      be targets for vaccine development.

PMID- 21078856
TI  - Identification of a family of effectors secreted by the type III secretion system
      that are conserved in pathogenic Chlamydiae.
AB  - Chlamydiae are Gram-negative, obligate intracellular pathogens that replicate
      within a membrane-bounded compartment termed an inclusion. Throughout their
      development, they actively modify the eukaryotic environment. The type III
      secretion (TTS) system is the main process by which the bacteria translocate
      effector proteins into the inclusion membrane and the host cell cytoplasm. Here
      we describe a family of type III secreted effectors that are present in all
      pathogenic chlamydiae and absent in the environment-related species. It is
      defined by a common domain of unknown function, DUF582, that is present in four
      or five proteins in each Chlamydiaceae species. We show that the amino-terminal
      extremity of DUF582 proteins functions as a TTS signal. DUF582 proteins from C.
      trachomatis CT620, CT621, and CT711 are expressed at the middle and late phases
      of the infectious cycle. Immunolocalization further revealed that CT620 and CT621
      are secreted into the host cell cytoplasm, as well as within the lumen of the
      inclusion, where they do not associate with bacterial markers. Finally, we show
      that DUF582 proteins are present in nuclei of infected cells, suggesting that
      members of the DUF582 family of effector proteins may target nuclear cell
      functions. The expansion of this family of proteins in pathogenic chlamydiae and
      their conservation among the different species suggest that they play important
      roles in the infectious cycle.

PMID- 21078857
TI  - Role of Tannerella forsythia NanH sialidase in epithelial cell attachment.
AB  - Tannerella forsythia is a Gram-negative oral anaerobe which contributes to the
      development of periodontitis, an inflammatory disease of the tooth-supporting
      tissues leading to tooth loss. The mechanisms by which this bacterium colonizes
      the oral cavity are poorly understood. The bacterium has been shown to express
      two distinct sialidases, namely, SiaHI and NanH, with the latter being the major
      sialidase. Bacterial sialidases can play roles in pathogenesis by cleaving sialic
      acids on host glycoproteins, destroying their integrity, and/or unmasking hidden
      epitopes on host surfaces for colonization. In the present study, we investigated
      the roles of the SiaHI and NanH sialidases by generating and characterizing
      specific deletion mutants. Our results showed that the NanH deficiency resulted
      in a total loss of sialidase activity associated with the outer-membrane and
      secreted fractions. On the other hand, the SiaHI deficiency resulted in only a
      slight reduction in the total sialidase activity, with no significant differences
      in the levels of sialidase activity in the outer membrane or secreted fractions
      compared to that in the wild-type strain. The results demonstrated that NanH is
      both surface localized and secreted. The NanH-deficient mutant but not the SiaHI
      deficient mutant was significantly attenuated in epithelial cell binding and
      invasion abilities compared to the wild-type strain. Moreover, the NanH-deficient
      mutant alone was impaired in cleaving surface sialic acids on epithelial cells.
      Thus, our study suggests that NanH sialidase might play roles in bacterial
      colonization by exposing sialic acid-hidden epitopes on epithelial cells.

PMID- 21078858
TI  - MyD88 deficiency leads to decreased NK cell gamma interferon production and T
      cell recruitment during Chlamydia muridarum genital tract infection, but a
      predominant Th1 response and enhanced monocytic inflammation are associated with
      infection resolution.
AB  - We have previously shown that MyD88 knockout (KO) mice exhibit delayed clearance
      of Chlamydia muridarum genital infection compared to wild-type (WT) mice. A
      blunted Th1 response and ineffective suppression of the Th2 response were also
      observed in MyD88 KO mice. The goal of the present study was to investigate
      specific mechanisms whereby absence of MyD88 leads to these effects and address
      the compensatory mechanisms in the genital tract that ultimately clear infection
      in the absence of MyD88. It was observed that NK cells recruited to the genital
      tract in MyD88 KO mice failed to produce gamma interferon (IFN-gamma) mRNA and
      protein. This defect was associated with decreased local production of
      interleukin-17 (IL-17), IL-18, and tumor necrosis factor alpha (TNF-alpha) but
      normal levels of IL-12p70. Additionally, recruitment of CD4 T cells to the
      genital tract was reduced in MyD88 KO mice compared to that in WT mice. Although
      chronic infection in MyD88 KO mice resulted in oviduct pathology comparable to
      that of WT mice, increased histiocytic inflammation was observed in the uterine
      horns. This was associated with increased CCL2 levels and recruitment of
      macrophages as a potential compensatory mechanism. Further deletion of TLR4-TRIF
      signaling in MyD88 KO mice, using TLR4/MyD88 double-KO mice, did not further
      compromise host defense against chlamydiae, suggesting that compensatory
      mechanisms are Toll-like receptor (TLR) independent. Despite some polarization
      toward a Th2 response, a Th1 response remained predominant in the absence of
      MyD88, and it provided equivalent protection against a secondary infection as
      observed in WT mice.

PMID- 21078859
TI  - Coxiella burnetii acid phosphatase inhibits the release of reactive oxygen
      intermediates in polymorphonuclear leukocytes.
AB  - Coxiella burnetii, the etiological agent of Q fever, is a small, Gram-negative,
      obligate intracellular bacterium. Replication of C. burnetii during infection has
      been shown to be increased by decreasing oxidative stress using p47(phox -/-) and
      iNOS(-/-) mice in vivo and by pharmacologic inhibitors in vitro. Building upon
      this model, we investigated the role polymorphonuclear leukocytes (PMN) play in
      the control of infection, since NADPH oxidase-mediated release of reactive oxygen
      intermediates (ROI) is a primary bactericidal mechanism for these cells that is
      critical for early innate clearance. Earlier studies suggested that C. burnetii
      actively inhibited release of ROI from PMN through expression of an unidentified
      acid phosphatase (ACP). Recent genomic annotations identified one open reading
      frame (CBU0335) which may encode a Sec- and type II-dependent secreted ACP. To
      test this model, viable C. burnetii propagated in tissue culture host cells or
      axenic media, C. burnetii extracts, or purified recombinant ACP (rACP) was
      combined with human PMN induced with 4-phorbol 12-myristate 13-acetate (PMA). The
      release of ROI was inhibited when PMN were challenged with viable C. burnetii, C.
      burnetii extracts, or rACP but not when PMN were challenged with electron beam
      inactivated C. burnetii. C. burnetii extracts and rACP were also able to inhibit
      PMA-induced formation of NADPH oxidase complex on PMN membranes, suggesting a
      molecular mechanism responsible for this inhibition. These data support a model
      in which C. burnetii eludes the primary ROI killing mechanism of activated PMN by
      secreting at least one acid phosphatase.

PMID- 21078860
TI  - CsrA modulates levels of lipoproteins and key regulators of gene expression
      critical for pathogenic mechanisms of Borrelia burgdorferi.
AB  - Carbon storage regulator A (CsrA) is an RNA binding protein that has been
      characterized in many bacterial species to play a central regulatory role by
      modulating several metabolic processes. We recently showed that a homolog of CsrA
      in Borrelia burgdorferi (CsrA(Bb), BB0184) was upregulated in response to
      propagation of B. burgdorferi under mammalian host-specific conditions. In order
      to further delineate the role of CsrA(Bb), we generated a deletion mutant
      designated ES10 in a linear plasmid 25-negative isolate of B. burgdorferi strain
      B31 (ML23). The deletion mutant was screened by PCR and Southern blot
      hybridization, and a lack of synthesis of CsrA(Bb) in ES10 was confirmed by
      immunoblot analysis. Analysis of ES10 propagated at pH 6.8/37 degrees C revealed
      a significant reduction in the levels of OspC, DbpA, BBK32, and BBA64 compared to
      those for the parental wild-type strain propagated under these conditions, while
      there were no significant changes in the levels of either OspA or P66. Moreover,
      the levels of two regulatory proteins, RpoS and BosR, were also found to be lower
      in ES10 than in the control strain. Quantitative real-time reverse transcription
      PCR analysis of total RNA extracted from the parental strain and csrA(Bb) mutant
      revealed significant differences in gene expression consistent with the changes
      at the protein level. Neither the csrA(Bb) mutant nor the trans-complemented
      strain was capable of infection following intradermal needle inoculation in
      C3H/HeN mice at either 103 or 105 spirochetes per mouse. The further
      characterization of molecular basis of regulation mediated by CsrA(Bb) will
      provide significant insights into the pathophysiology of B. burgdorferi.

PMID- 21078861
TI  - Francisella tularensis Schu S4 O-antigen and capsule biosynthesis gene mutants
      induce early cell death in human macrophages.
AB  - Francisella tularensis is capable of rampant intracellular growth and causes a
      potentially fatal disease in humans. Whereas many mutational studies have been
      performed with avirulent strains of Francisella, relatively little has been done
      with strains that cause human disease. We generated a near-saturating transposon
      library in the virulent strain Schu S4, which was subjected to high-throughput
      screening by transposon site hybridization through primary human macrophages,
      negatively selecting 202 genes. Of special note were genes in a locus of the
      Francisella chromosome, FTT1236, FTT1237, and FTT1238. Mutants with mutations in
      these genes demonstrated significant sensitivity to complement-mediated lysis
      compared with wild-type Schu S4 and exhibited marked defects in O-antigen and
      capsular polysaccharide biosynthesis. In the absence of complement, these mutants
      were phagocytosed more efficiently by macrophages than wild-type Schu S4 and were
      capable of phagosomal escape but exhibited reduced intracellular growth.
      Microscopic and quantitative analyses of macrophages infected with mutant
      bacteria revealed that these macrophages exhibited signs of cell death much
      earlier than those infected with Schu S4. These data suggest that FTT1236,
      FTT1237, and FTT1238 are important for polysaccharide biosynthesis and that the
      Francisella O antigen, capsule, or both are important for avoiding the early
      induction of macrophage death and the destruction of the replicative niche.

PMID- 21078862
TI  - The importance of energy balance in improving photosynthetic productivity.

PMID- 21078863
TI  - Optimizing antenna size to maximize photosynthetic efficiency.

PMID- 21078864
TI  - Stable isotopes reveal the contribution of corticular photosynthesis to growth in
      branches of Eucalyptus miniata.
AB  - The deciduous bark habit is widespread in the woody plant genus Eucalyptus.
      Species with deciduous bark seasonally shed a layer of dead bark, thereby
      maintaining smooth-bark surfaces on branches and stems as they age and increase
      in diameter. This has a significant cost in terms of fire protection, because
      smooth-barked species have thinner bark than rough-barked species that accumulate
      successive layers of dead bark. Eucalypts are closely associated with fire,
      suggesting that the smooth-bark habit must also provide a significant benefit. We
      suggest that this benefit is corticular photosynthesis. To test this, we
      quantified the contribution of corticular photosynthesis to wood production in
      smooth-barked branches of Eucalyptus miniata growing in tropical savanna in
      northern Australia. We covered branch sections with aluminum foil for 4 years to
      block corticular photosynthesis and then compared the oxygen and carbon stable
      isotope composition of foil-covered and uncovered branch sections. We developed
      theory to calculate the proportion of wood constructed from corticular
      photosynthate and the mean proportional refixation rate during corticular
      photosynthesis from the observed isotopic differences. Coverage with aluminum
      foil for 4 years increased wood delta(13)C by 0.50/00 (P = 0.002, n = 6) and wood
      delta(18)O by 0.50/00 (P = 0.02, n = 6). Based on these data, we estimated that
      11% +/- 3% of wood in the uncovered branch sections was constructed from
      corticular photosynthate, with a mean delta(13)C of -34.80/00, and that the mean
      proportional refixation rate during corticular photosynthesis was 0.71 +/- 0.15.
      This demonstrates that corticular photosynthesis makes a significant contribution
      to the carbon economy of smooth-barked eucalypts.

PMID- 21078866
TI  - Management of severe hand wounds with Integra(r) dermal regeneration template.
AB  - We report our experience with the use of Integra(r) for the management of severe
      traumatic wounds of the hand. Fifteen patients were treated with follow-up
      ranging from 10 to 37 months. Wounds were associated with an osseous and/or joint
      and/or tendon exposure. Following Integra(r) placement, patients were managed
      with dressings and subsequent split-thickness skin grafting an average of 26 days
      later. Integra(r) was successful in achieving durable, functional and aesthetic
      definitive coverage in 13 of 15 applications while allowing a satisfying
      pollicidigital prehension. Regarding our clinical experience, Integra(r) is an
      effective technique to deal with severe wounds of the hand with exposed tendon
      and/or bone and/or joint, even in the absence of paratenon or periosteum. This
      can potentially lessen the need for local rotational or free flap coverage and
      should be taken into consideration as a viable alternative in traumatic
      reconstruction of the hand.

PMID- 21078867
TI  - On the mechanism of CFTR inhibition by a thiazolidinone derivative.
AB  - The effects of a thiazolidinone derivative, 3-[(3-trifluoromethyl)phenyl]-5-[(4
      carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (or CFTRinh-172), on cystic
      fibrosis transmembrane conductance regulator (CFTR) gating were studied in
      excised inside-out membrane patches from Chinese hamster ovary cells transiently
      expressing wild-type and mutant CFTR. We found that the application of CFTRinh
      172 results in an increase of the mean closed time and a decrease of the mean
      open time of the channel. A hyperbolic relationship between the closing rate and
      [CFTRinh-172] suggests that CFTRinh-172 does not act as a simple pore blocker.
      Interestingly, the potency of inhibition increases as the open time of the
      channel is increased with an IC50 in the low nanomolar range for CFTR channels
      locked in an open state for tens of seconds. Our studies also provide evidence
      that CFTRinh-172 can bind to both the open state and the closed state. However,
      at least one additional step, presumably reflecting inhibitor-induced
      conformational changes, is required to shut down the conductance after the
      binding of the inhibitor to the channel. Using the hydrolysis-deficient mutant
      E1371S as a tool as the closing rate of this mutant is dramatically decreased, we
      found that CFTRinh-172-dependent inhibition of CFTR channel gating, in two
      aspects, mimics the inactivation of voltage-dependent cation channels. First,
      similar to the recovery from inactivation in voltage-gated channels, once CFTR is
      inhibited by CFTRinh-172, reopening of the channel can be seen upon removal of
      the inhibitor in the absence of adenosine triphosphate (ATP). Second, ATP induced
      a biphasic current response on inhibitor-bound closed channels as if the ATP
      opened channels "inactivate" despite a continuous presence of ATP. A simplified
      six-state kinetic scheme can well describe our data, at least qualitatively.
      Several possible structural mechanisms for the effects of CFTRinh-172 will be
      discussed.

PMID- 21078868
TI  - Relative motion of transmembrane segments S0 and S4 during voltage sensor
      activation in the human BK(Ca) channel.
AB  - Large-conductance voltage- and Ca(2+)-activated K(+) (BK(Ca)) channel alpha
      subunits possess a unique transmembrane helix referred to as S0 at their N
      terminus, which is absent in other members of the voltage-gated channel
      superfamily. Recently, S0 was found to pack close to transmembrane segments S3
      and S4, which are important components of the BK(Ca) voltage-sensing apparatus.
      To assess the role of S0 in voltage sensitivity, we optically tracked protein
      conformational rearrangements from its extracellular flank by site-specific
      labeling with an environment-sensitive fluorophore, tetramethylrhodamine
      maleimide (TMRM). The structural transitions resolved from the S0 region
      exhibited voltage dependence similar to that of charge-bearing transmembrane
      domains S2 and S4. The molecular determinant of the fluorescence changes was
      identified in W203 at the extracellular tip of S4: at hyperpolarized potential,
      W203 quenches the fluorescence of TMRM labeling positions at the N-terminal flank
      of S0. We provide evidence that upon depolarization, W203 (in S4) moves away from
      the extracellular region of S0, lifting its quenching effect on TMRM
      fluorescence. We suggest that S0 acts as a pivot component against which the
      voltage-sensitive S4 moves upon depolarization to facilitate channel activation.

PMID- 21078870
TI  - Relaxing messages from the sarcolemma.

PMID- 21078869
TI  - Sarcolemmal-restricted localization of functional ClC-1 channels in mouse
      skeletal muscle.
AB  - Skeletal muscle fibers exhibit a high resting chloride conductance primarily
      determined by ClC-1 chloride channels that stabilize the resting membrane
      potential during repetitive stimulation. Although the importance of ClC-1 channel
      activity in maintaining normal muscle excitability is well appreciated, the
      subcellular location of this conductance remains highly controversial. Using a
      three-pronged multidisciplinary approach, we determined the location of
      functional ClC-1 channels in adult mouse skeletal muscle. First, formamide
      induced detubulation of single flexor digitorum brevis (FDB) muscle fibers from
      15-16-day-old mice did not significantly alter macroscopic ClC-1 current
      magnitude (at -140 mV; -39.0 +/- 4.5 and -42.3 +/- 5.0 nA, respectively),
      deactivation kinetics, or voltage dependence of channel activation (V(1/2) was 
      61.0 +/- 1.7 and -64.5 +/- 2.8 mV; k was 20.5 +/- 0.8 and 22.8 +/- 1.2 mV,
      respectively), despite a 33% reduction in cell capacitance (from 465 +/- 36 to
      312 +/- 23 pF). In paired whole cell voltage clamp experiments, where ClC-1
      activity was measured before and after detubulation in the same fiber, no
      reduction in ClC-1 activity was observed, despite an approximately 40 and 60%
      reduction in membrane capacitance in FDB fibers from 15-16-day-old and adult
      mice, respectively. Second, using immunofluorescence and confocal microscopy,
      native ClC-1 channels in adult mouse FDB fibers were localized within the
      sarcolemma, 90 degrees out of phase with double rows of dihydropyridine receptor
      immunostaining of the T-tubule system. Third, adenoviral-mediated expression of
      green fluorescent protein-tagged ClC-1 channels in adult skeletal muscle of a
      mouse model of myotonic dystrophy type 1 resulted in a significant reduction in
      myotonia and localization of channels to the sarcolemma. Collectively, these
      results demonstrate that the majority of functional ClC-1 channels localize to
      the sarcolemma and provide essential insight into the basis of myofiber
      excitability in normal and diseased skeletal muscle.

PMID- 21078871
TI  - Unitary Ca(2+) current through recombinant type 3 InsP(3) receptor channels under
      physiological ionic conditions.
AB  - The ubiquitous inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R)
      channel, localized primarily in the endoplasmic reticulum (ER) membrane, releases
      Ca(2+) into the cytoplasm upon binding InsP(3), generating and modulating
      intracellular Ca(2+) signals that regulate numerous physiological processes.
      Together with the number of channels activated and the open probability of the
      active channels, the size of the unitary Ca(2+) current (i(Ca)) passing through
      an open InsP(3)R channel determines the amount of Ca(2+) released from the ER
      store, and thus the amplitude and the spatial and temporal nature of Ca(2+)
      signals generated in response to extracellular stimuli. Despite its significance,
      i(Ca) for InsP(3)R channels in physiological ionic conditions has not been
      directly measured. Here, we report the first measurement of i(Ca) through an
      InsP(3)R channel in its native membrane environment under physiological ionic
      conditions. Nuclear patch clamp electrophysiology with rapid perfusion solution
      exchanges was used to study the conductance properties of recombinant
      homotetrameric rat type 3 InsP(3)R channels. Within physiological ranges of free
      Ca(2+) concentrations in the ER lumen ([Ca(2+)](ER)), free cytoplasmic [Ca(2+)]
      ([Ca(2+)](i)), and symmetric free [Mg(2+)] ([Mg(2+)](f)), the i(Ca)-[Ca(2+)](ER)
      relation was linear, with no detectable dependence on [Mg(2+)](f). i(Ca) was 0.15
      +/- 0.01 pA for a filled ER store with 500 microM [Ca(2+)](ER). The i(Ca)
      [Ca(2+)](ER) relation suggests that Ca(2+) released by an InsP(3)R channel raises
      [Ca(2+)](i) near the open channel to approximately 13-70 microM, depending on
      [Ca(2+)](ER). These measurements have implications for the activities of nearby
      InsP(3)-liganded InsP(3)R channels, and they confirm that Ca(2+) released by an
      open InsP(3)R channel is sufficient to activate neighboring channels at
      appropriate distances away, promoting Ca(2+)-induced Ca(2+) release.

PMID- 21078872
TI  - A subset of Drosophila integrator proteins is essential for efficient U7 snRNA
      and spliceosomal snRNA 3'-end formation.
AB  - Proper gene expression relies on a class of ubiquitously expressed, uridine-rich
      small nuclear RNAs (snRNAs) transcribed by RNA polymerase II (RNAPII). Vertebrate
      snRNAs are transcribed from a unique promoter, which is required for proper 3'
      end formation, and cleavage of the nascent transcript involves the activity of a
      poorly understood set of proteins called the Integrator complex. To examine 3'
      end formation in Drosophila melanogaster, we developed a cell-based reporter that
      monitors aberrant 3'-end formation of snRNA through the gain in expression of
      green fluorescent protein (GFP). We used this reporter in Drosophila S2 cells to
      determine requirements for U7 snRNA 3'-end formation and found that processing
      was strongly dependent upon nucleotides located within the 3' stem-loop as well
      as sequences likely to comprise the Drosophila equivalent of the vertebrate 3'
      box. Substitution of the actin promoter for the snRNA promoter abolished proper
      3'-end formation, demonstrating the conserved requirement for an snRNA promoter
      in Drosophila. We tested the requirement for all Drosophila Integrator subunits
      and found that Integrators 1, 4, 9, and 11 were essential for 3'-end formation
      and that Integrators 3 and 10 may be dispensable for processing. Depletion of
      cleavage and polyadenylation factors or of histone pre-mRNA processing factors
      did not affect U7 snRNA processing efficiency, demonstrating that the Integrator
      complex does not share components with the mRNA 3'-end processing machinery.
      Finally, flies harboring mutations in either Integrator 4 or 7 fail to complete
      development and accumulate significant levels of misprocessed snRNA in the larval
      stages.

PMID- 21078873
TI  - Conserved catalytic and C-terminal regulatory domains of the C-terminal binding
      protein corepressor fine-tune the transcriptional response in development.
AB  - Transcriptional corepressors play complex roles in developmental gene regulation.
      These proteins control transcription by recruiting diverse chromatin-modifying
      enzymes, but it is not known whether corepressor activities are finely regulated
      in different developmental settings or whether their basic activities are
      identical in most contexts. The evolutionarily conserved C-terminal binding
      protein (CtBP) is recruited by a variety of transcription factors that play
      crucial roles in development and disease. CtBP contains a central NAD(H) binding
      core domain that is homologous to D2 hydroxy acid dehydrogenase enzymes, as well
      as an unstructured C-terminal domain. NAD(H) binding is important for CtBP
      function, but the significance of its intrinsic dehydrogenase activity, as well
      as that of the unstructured C terminus, is poorly understood. To clarify the
      biological relevance of these features, we established genetic rescue assays to
      determine how different forms of CtBP function in the context of Drosophila
      melanogaster development. The mutant phenotypes and specific gene regulatory
      effects indicate that both the catalytic site of CtBP and the C-terminal
      extension play important, if nonessential roles in development. Our results
      indicate that the structural and enzymatic features of CtBP, previously thought
      to be dispensable for overall transcriptional control, are critical for
      modulating this protein's activity in diverse developmental settings.

PMID- 21078874
TI  - CARHSP1 is required for effective tumor necrosis factor alpha mRNA stabilization
      and localizes to processing bodies and exosomes.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a critical mediator of inflammation,
      and its production is tightly regulated, with control points operating at nearly
      every step of its biosynthesis. We sought to identify uncharacterized TNF-alpha
      3' untranslated region (3'UTR)-interacting proteins utilizing a novel screen,
      termed the RNA capture assay. We identified CARHSP1, a cold-shock domain
      containing protein. Knockdown of CARHSP1 inhibits TNF-alpha protein production in
      lipopolysaccharide (LPS)-stimulated cells and reduces the level of TNF-alpha mRNA
      in both resting and LPS-stimulated cells. mRNA stability assays demonstrate that
      CARHSP1 knockdown decreases TNF-alpha mRNA stability from a half-life (t(1/2)) of
      49 min to a t(1/2) of 22 min in LPS-stimulated cells and from a t(1/2) of 29 min
      to a t(1/2) of 24 min in resting cells. Transfecting CARHSP1 into RAW264.7 cells
      results in an increase in TNF-alpha 3'UTR luciferase expression in resting cells
      and CARHSP1 knockdown LPS-stimulated cells. We examined the functional effect of
      inhibiting Akt, calcineurin, and protein phosphatase 2A and established that
      inhibition of Akt or calcineurin but not PP2A inhibits CARHSP1 function.
      Subcellular analysis establishes CARHSP1 as a cytoplasmic protein localizing to
      processing bodies and exosomes but not on translating mRNAs. We conclude CARHSP1
      is a TNF-alpha mRNA stability enhancer required for effective TNF-alpha
      production, demonstrating the importance of both stabilization and
      destabilization pathways in regulating the TNF-alpha mRNA half-life.

PMID- 21078875
TI  - Cyclin A promotes S-phase entry via interaction with the replication licensing
      factor Mcm7.
AB  - Cyclin A is known to promote S-phase entry in mammals, but its critical targets
      in this process have not been defined. We derived a novel human cyclin A mutant
      (CycA-C1), which can activate cyclin-dependent kinase but cannot promote S-phase
      entry, and isolated replication licensing factor Mcm7 as a factor that interacts
      with the wild-type cyclin A but not with the mutant. We demonstrated that human
      cyclin A and Mcm7 interact in the chromatin fraction. To address the
      physiological significance of the cyclin A-Mcm7 interaction, we isolated an Mcm7
      mutant (Mcm7-3) that is capable of association with CycA-C1 and found that it can
      also suppress the deficiency of CycA-C1 in promoting S-phase entry. Finally, RNA
      interference experiments showed that the CycA-C1 mutant is defective for the
      endogenous cyclin A function in S-phase entry and that this defect can be
      suppressed by the Mcm7-3 mutant. Our findings demonstrate that interaction with
      Mcm7 is essential for the function of cyclin A in promoting S-phase entry.

PMID- 21078876
TI  - Expression of type II chorionic gonadotropin genes supports a role in the male
      reproductive system.
AB  - Human chorionic gonadotropin (hCG) is a glycoprotein hormone essential to
      pregnancy. hCG is heterodimeric and functionally defined by its beta subunit.
      hCGbeta evolved from the beta subunit of luteinizing hormone in two phases. In
      the first phase, type I genes (hCGbeta3, -5, -7, and -8) acquired changes
      affecting gene expression and extending the proteins' C terminus. In the second
      phase, type II genes (hCGbeta1 and -2) were formed by the insertion of a DNA
      element into the type I 5' end. The insertion includes the small noncoding RNA
      gene snaR-G and has been predicted to drastically change the protein products
      encoded. We trace the insertion to the common ancestor of the African great apes
      and show that it contains transcription signals, including snaR-G. Type II
      transcripts are predominantly expressed in testis. Contrary to predictions, the
      product of the major mRNA splice form is hCGbeta. A novel peptide is encoded by
      alternatively spliced transcripts. These findings support the view that type II
      genes evolved in African great apes to function in the male reproductive system.

PMID- 21078878
TI  - Atherosclerotic renal artery stenosis, the oculostenotic reflex, and therapeutic
      nihilism.

PMID- 21078877
TI  - Phosphorylation of tristetraprolin by MK2 impairs AU-rich element mRNA decay by
      preventing deadenylase recruitment.
AB  - mRNA turnover is a critical step in the control of gene expression. In mammalian
      cells, a subset of mRNAs regulated at the level of mRNA turnover contain
      destabilizing AU-rich elements (AREs) in their 3' untranslated regions. These
      transcripts are bound by a suite of ARE-binding proteins (AUBPs) that receive
      information from cell signaling events to modulate rates of ARE mRNA decay. Here
      we show that a key destabilizing AUBP, tristetraprolin (TTP), is repressed by the
      p38 mitogen-activated protein kinase (MAPK)-activated kinase MK2 due to the
      inability of phospho-TTP to recruit deadenylases to target mRNAs. TTP is tightly
      associated with cytoplasmic deadenylases and promotes rapid deadenylation of
      target mRNAs both in vitro and in cells. TTP can direct the deadenylation of
      substrate mRNAs when tethered to a heterologous mRNA, yet its ability to do so is
      inhibited upon phosphorylation by MK2. Phospho-TTP is not impaired in mRNA
      binding but does fail to recruit the major cytoplasmic deadenylases. These
      observations suggest that phosphorylation of TTP by MK2 primarily affects mRNA
      decay downstream of RNA binding by preventing recruitment of the deadenylation
      machinery. Thus, TTP may remain poised to rapidly reactivate deadenylation of
      bound transcripts to downregulate gene expression once the p38 MAPK pathway is
      deactivated.

PMID- 21078879
TI  - Translesional pressure gradients to predict blood pressure response after renal
      artery stenting in patients with renovascular hypertension.
AB  - BACKGROUND: In previous studies on the effect of renal stenting on arterial
      hypertension, patients were selected mainly on the basis of angiographic
      parameters of the renal artery stenosis. The aim of the present study was to
      evaluate whether translesional pressure gradients could identify the patients
      with renal artery stenosis who might benefit from stenting. METHODS AND RESULTS:
      A total of 53 consecutive hypertensive patients with unilateral RAS scheduled for
      renal artery intervention were recruited. Transstenotic pressure gradients were
      measured at baseline and during maximal hyperemia, before renal artery stenting.
      Twenty-four-hour ambulatory blood pressure measurements were performed in all
      patients before and 3 months after the intervention. Average reductions in
      systolic blood pressure and diastolic blood pressure at follow-up were -20+/-30
      mm Hg and -2+/-12 mm Hg, respectively. At multivariate analysis, dopamine-induced
      mean gradient was the only independent predictor of the variations of both
      systolic blood pressure (regression coefficient=-4.03, standard error=1.11;
      P<0.001) and diastolic blood pressure (regression coefficient=-3.11, standard
      error=1.20; P=0.009). Patients who showed a decline in systolic blood pressure
      from the baseline value >20 mm Hg were considered as "responders." The optimal
      cutoff for identification of "responders" was a dopamine-induced mean gradient
      >=20 mm Hg (area under the curve, 0.77; 95% confidence interval, 0.64 to 0.90;
      P=0.001). CONCLUSIONS: A dopamine-induced mean pressure gradient of >=20 mm Hg is
      highly predictive of arterial hypertension improvement after renal stenting, and
      therefore this measurement is useful for appropriate selection of patients with
      arterial hypertension.

PMID- 21078880
TI  - The effects of a high-fat, high-cholesterol diet on markers of uterine
      contractility during parturition in the rat.
AB  - Increasing levels of obesity within women of reproductive age is a major concern
      in the UK. Approximately, 13% of women aged <30 and 22% of 31- to 40-year-old
      women are obese. Obesity increases complications during pregnancy and the risk of
      caesarean section due to prolonged labour and poor uterine activity. The aim was
      to investigate whether a high-fat, high-cholesterol (HFHC) diet decreases markers
      of uterine contractility during parturition in the rat. Female Wistar rats were
      fed control (CON, n=10) or HFHC (n=10) diets for 6 weeks. Animals were mated and,
      once pregnant, maintained on their diet throughout gestation. On gestational day
      19, rats were monitored continuously and killed at the onset of parturition. Body
      and fat depot weights were recorded. Myometrial tissue was analysed for
      cholesterol (CHOL), triglycerides (TAG), and expression of the contractile
      associated proteins gap junction protein alpha 1 (GJA1; also known as connexin
      43, CX-43), prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclo
      oxygenase-2, COX-2) and caveolin-1 (CAV1) and maternal plasma for prostaglandin
      F(2)(alpha) (PGF(2)(alpha)) and progesterone. HFHC fed rats gained greater weight
      than CON (P<0.003) with significant increases in peri-renal fat (P<0.01). The
      HFHC diet increased plasma CHOL, TAG and progesterone, but decreased
      PGF(2)(alpha) versus CON (P<0.01, P<0.01, P=0.05 and P<0.02 respectively). Total
      CHOL and TAG levels of uterine tissue were similar. However, HFHC fed rats showed
      significant increases in PTGS2 (P<0.037), but decreases in GJA1 and CAV1
      (P=0.059). In conclusion, a HFHC diet significantly increases body weight and
      alters lipid profiles that correlate with decreases in key markers of uterine
      contractility. Further work is required to ascertain whether these changes have
      adverse effects on uterine activity.

PMID- 21078881
TI  - Canine subcutaneous mast cell tumor: characterization and prognostic indices.
AB  - Histologic grading schemes for canine cutaneous mast cell tumors (MCTs) were not
      developed for subcutaneous MCTs. Despite this, subcutaneous MCTs are currently
      categorized by many as grade II or higher. The aim of this investigation was to
      assess the pathology and clinical outcome for subcutaneous MCTs to provide a more
      accurate prognosis. Information on clinical outcome for 306 dogs was obtained
      from veterinarians and correlated with histologic features. Mean and median
      follow-up was 842 and 891 days, respectively (range, 3-2,305 days). Only 27 (9%)
      were confirmed as mast cell-related deaths. Metastasis occurred in 13 (4%), and
      24 (8%) had local reoccurrence, even though 171 (56%) cases had incomplete
      surgical margins. Median survival time was not reached, and the estimated 6
      month, 1-, 2-, and 5-year survival probabilities were 95%, 93%, 92%, and 86%,
      respectively. Dogs were euthanized or died as a result of local tumor
      reoccurrence, additional MCT development distant to the surgical site, or
      metastasis. Decreased survival time was linked to mitotic index (number of
      mitotic figures per 10 high-power fields), infiltrative growth pattern, and
      presence of multinucleation. Both univariable and multivariable analysis showed
      mitotic index to be strongly predictive of survival, local reoccurrence, and
      metastasis. The results of the study indicate that the majority of subcutaneous
      MCTs have a favorable prognosis, with extended survival times and low rates of
      reoccurrence and metastasis.

PMID- 21078882
TI  - Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms.
AB  - Definitive diagnosis of canine oral melanocytic neoplasms is often difficult
      because of variability in pigmentation and cellular pleomorphism. These neoplasms
      can resemble carcinomas, sarcomas, and round cell neoplasms, which differ in
      prognosis and treatment. A variety of immunohistochemical antibodies have been
      used for diagnosis of melanocytic neoplasms in humans and dogs; however,
      sensitivity and specificity of many markers have not been determined in
      amelanotic melanocytic neoplasms in dogs. The authors investigated a
      comprehensive panel of immunohistochemical markers in 49 canine oral amelanotic
      melanocytic neoplasms--namely, Melan-A, PNL2, HMB-45, microphthalmia
      transcription factor (MiTF), S-100, tyrosine hydroxylase, tyrosinase, tyrosinase
      related proteins 1 and 2 (TRP-1 and TRP-2), and CD34. Ten well-differentiated
      cutaneous soft tissue spindle cell sarcomas were negative controls. Melan-A,
      PNL2, TRP-1, and TRP-2 were highly sensitive and 100% specific for the diagnosis
      of canine oral amelanotic melanocytic neoplasms. S-100 and MiTF showed high
      sensitivity but were less specific; that is, they also labeled a proportion of
      the soft tissue spindle cell sarcomas. HMB-45, tyrosinase, and tyrosine
      hydroxylase were 100% specific but had low sensitivities. CD34 did not label any
      of the melanocytic neoplasms but did label 80% of the soft tissue spindle cell
      sarcomas. A cost-effective and efficient immunodiagnostic cocktail containing
      antibodies against PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100%
      specificity and 93.9% sensitivity in identifying canine oral amelanotic
      melanocytic neoplasms. The spindloid variant was the variant with the lowest
      sensitivity to the cocktail. The likelihood of correctly diagnosing canine oral
      amelanotic melanocytic neoplasms was dramatically higher when biopsy samples
      contained ample overlying and adjacent epithelium.

PMID- 21078883
TI  - Experimental classical bovine spongiform encephalopathy: definition and
      progression of neural PrP immunolabeling in relation to diagnosis and disease
      controls.
AB  - Tissues from sequential-kill time course studies of bovine spongiform
      encephalopathy (BSE) were examined to define PrP immunohistochemical labeling
      forms and map disease-specific labeling over the disease course after oral
      exposure to the BSE agent at two dose levels. Study was confined to brainstem,
      spinal cord, and certain peripheral nervous system ganglia-tissues implicated in
      pathogenesis and diagnosis or disease control strategies. Disease-specific
      labeling in the brainstem in 39 of 220 test animals showed the forms and patterns
      observed in natural disease and invariably preceded spongiform changes. A precise
      temporal pattern of increase in labeling was not apparent, but labeling was
      generally most widespread in clinical cases, and it always involved neuroanatomic
      locations in the medulla oblongata. In two cases, sparse labeling was confined to
      one or more neuroanatomic nuclei of the medulla oblongata. When involved, the
      spinal cord was affected at all levels, providing no indication of temporal
      spread within the cord axis or relative to the brainstem. Where minimal PrP
      labeling occurred in the thoracic spinal cord, it was consistent with initial
      involvement of general visceral efferent neurons. Labeling of ganglia involved
      only sensory ganglia and only when PrP was present in the brainstem and spinal
      cord. These experimental transmissions mimicked the neuropathologic findings in
      BSE-C field cases, independent of dose of agent or stage of disease. The model
      supports current diagnostic sampling approaches and control measures for the
      removal and destruction of nervous system tissues in slaughtered cattle.

PMID- 21078884
TI  - Differential signaling of cysteinyl leukotrienes and a novel cysteinyl
      leukotriene receptor 2 (CysLT2) agonist, N-methyl-leukotriene C4, in calcium
      reporter and beta arrestin assays.
AB  - The cysteinyl leukotrienes (cysLTs) LTC4, LTD4, and LTE4 are lipid mediators with
      physiological and pathophysiological functions. They exert their effects through
      G protein-coupled receptors (GPCRs), most notably via CysLT1 and CysLT2 receptor.
      The roles of the CysLT2 receptor are beginning to emerge. Both LTC4 and LTD4 are
      potent agonists for the CysLT2 receptor; however, LTC4 is rapidly converted to
      LTD4, which is also the main endogenous ligand for the CysLT1 receptor. A
      selective and potent agonist at the CysLT2 receptor would facilitate studies to
      discern between receptor subtypes. We show here that N-methyl LTC4 (NMLTC4), a
      metabolically stable LTC4 mimetic, is a potent and selective CysLT2 receptor
      agonist. Two expression systems were used to evaluate the functional activity of
      NMLTC4 at human and/or mouse CysLT1 and CysLT2 receptors. Through the aequorin
      cell-based assay for calcium-coupled GPCRs, NMLTC4 was almost equipotent to LTC4
      at CysLT2 receptors but was the least efficacious at CysLT2 receptors. In a beta
      galactosidase-beta-arrestin complementation assay, the human (h) CysLT2 receptor
      can couple with beta-arrestin-2, and NMLTC4 is slightly more potent for eliciting
      beta-arrestin-2 binding compared with cysLTs. Furthermore, LTE4 is nearly
      inactive in this assay compared with its weak partial agonist activity in the
      aequorin system. In a vascular leakage assay, NMLTC4 is potent and active in mice
      overexpressing hCysLT2 receptor in endothelium, whereas the response is abrogated
      in CysLT2 receptor knockout mice. Therefore, NMLTC4 is a potent subtype selective
      agonist for the CysLT2 receptor in vitro and in vivo, and it will be useful to
      elucidate its biological roles.

PMID- 21078885
TI  - Epidermal growth factor treatment switches delta-opioid receptor-stimulated
      extracellular signal-regulated kinases 1 and 2 signaling from an epidermal growth
      factor to an insulin-like growth factor-1 receptor-dependent mechanism.
AB  - delta-Opioid receptor (DOR)-induced activation of extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) is mediated by the transactivation of epidermal growth
      factor (EGF) receptors. Here we demonstrate that in stably DOR-expressing human
      embryonic kidney (HEK) 293 (HEK/DOR) cells, down-regulation of EGF receptors by
      long-term EGF (0.1 MUg for 18 h) treatment, but not by small interfering RNA,
      results in functional desensitization of EGF (10 ng/ml)-stimulated ERK1/2
      signaling. In EGF receptor-desensitized (HEK/DOR(-EGFR)) cells, however, [d
      Ala2,d-Leu5]enkephalin (1 MUM) and etorphine (0.1 MUM) retained their ability to
      stimulate ERK1/2 activation. The newly acquired signal transduction mechanism is
      insensitive to the EGF receptor blockers 4-(3-chloroanilino)-6,7
      dimethoxyquinazoline (AG1478) and N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2
      butynamide (CL-387,785), does not involve DOR internalization and activation of
      the focal adhesion kinase pp125FAK, but requires matrix metalloproteinase
      dependent release of soluble growth factors. A supernatant transfer assay in
      which conditioned growth media of opioid-treated HEK/DOR and HEK/DOR(-EGFR)
      "donor" cells are used to stimulate ERK1/2 activity in DOR-lacking HEK293 wild
      type and HEK293(-EGFR) "acceptor" cells revealed that long-term EGF treatment
      produces a switch in the receptor tyrosine kinase (RTK) system transactivated by
      opioids. Using microfluidic electrophoresis, chemical inhibitors, phosphorylation
      specific antibodies, and EGF receptor-deficient Chinese hamster ovary-K1 cells,
      we identified the release of an insulin-like growth factor-1 (IGF-1)-like peptide
      and activation of IGF-1 receptors in HEK/DOR(-EGFR) cells after DOR activation. A
      similar switch from a neurotrophic tyrosine kinase receptor type 1 to an IGF-1
      receptor-dependent ERK1/2 signaling was observed for chronically nerve growth
      factor-treated neuroblastoma * glioma (NG108-15) cells. These results indicate
      that transactivation of the dominant RTK system in a given cellular setting may
      represent a general feature of opioids to maintain mitogenic signaling.

PMID- 21078886
TI  - CD14 is a coreceptor of Toll-like receptors 7 and 9.
AB  - Recognition of pathogens by the innate immune system requires proteins that
      detect conserved molecular patterns. Nucleic acids are recognized by cytoplasmic
      sensors as well as by endosomal Toll-like receptors (TLRs). It has become evident
      that TLRs require additional proteins to be activated by their respective
      ligands. In this study, we show that CD14 (cluster of differentiation 14)
      constitutively interacts with the MyD88-dependent TLR7 and TLR9. CD14 was
      necessary for TLR7- and TLR9-dependent induction of proinflammatory cytokines in
      vitro and for TLR9-dependent innate immune responses in mice. CD14 associated
      with TLR9 stimulatory DNA in precipitation experiments and confocal imaging. The
      absence of CD14 led to reduced nucleic acid uptake in macrophages. Additionally,
      CD14 played a role in the stimulation of TLRs by viruses. Using various types of
      vesicular stomatitis virus, we showed that CD14 is dispensable for viral uptake
      but is required for the triggering of TLR-dependent cytokine responses. These
      data show that CD14 has a dual role in nucleic acid-mediated TLR activation: it
      promotes the selective uptake of nucleic acids, and it acts as a coreceptor for
      endosomal TLR activation.

PMID- 21078887
TI  - Cytomegalovirus immunoevasin reveals the physiological role of "missing self"
      recognition in natural killer cell dependent virus control in vivo.
AB  - Cytomegaloviruses (CMVs) are renowned for interfering with the immune system of
      their hosts. To sidestep antigen presentation and destruction by CD8(+) T cells,
      these viruses reduce expression of major histocompatibility complex class I (MHC
      I) molecules. However, this process sensitizes the virus-infected cells to
      natural killer (NK) cell-mediated killing via the "missing self" axis. Mouse
      cytomegalovirus (MCMV) uses m152 and m06 encoded proteins to inhibit surface
      expression of MHC I molecules. In addition, it encodes another protein, m04,
      which forms complexes with MHC I and escorts them to the cell surface. This
      mechanism is believed to prevent NK cell activation and killing by restoring the
      "self" signature and allowing the engagement of inhibitory Ly49 receptors on NK
      cells. Here we show that MCMV lacking m04 was attenuated in an NK cell- and MHC I
      dependent manner. NK cell-mediated control of the infection was dependent on the
      presence of NK cell subsets expressing different inhibitory Ly49 receptors. In
      addition to providing evidence for immunoevasion strategies used by CMVs to avoid
      NK cell control via the missing-self pathway, our study is the first to
      demonstrate that missing self-dependent NK cell activation is biologically
      relevant in the protection against viral infection in vivo.

PMID- 21078888
TI  - Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated
      suppression of interleukin 17 receptor signaling.
AB  - Interleukin 17 (IL-17) plays critical roles in the pathogenesis of various
      autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE).
      How the signals triggered by this powerful inflammatory cytokine are controlled
      to avoid abnormal inflammatory responses is not well understood. In this study,
      we report that TRAF3 is a receptor proximal negative regulator of IL-17 receptor
      (IL-17R) signaling. TRAF3 greatly suppressed IL-17-induced NF-kappaB and mitogen
      activated protein kinase activation and subsequent production of inflammatory
      cytokines and chemokines. Mechanistically, the binding of TRAF3 to IL-17R
      interfered with the formation of the receptor signaling activation complex IL-17R
      Act1-TRAF6, resulting in suppression of downstream signaling. TRAF3 markedly
      inhibited IL-17-induced expression of inflammatory cytokine and chemokine genes
      in vivo and consequently delayed the onset and greatly reduced the incidence and
      severity of EAE. Thus, TRAF3 is a negative regulator of IL-17R proximal
      signaling.

PMID- 21078889
TI  - Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host
      disease without global immunosuppression.
AB  - Graft-versus-host disease (GVHD) causes significant morbidity and mortality in
      allogeneic hematopoietic stem cell transplantation (aHSCT), preventing its
      broader application to non-life-threatening diseases. We show that a single
      administration of a nondepleting monoclonal antibody specific for the
      coinhibitory immunoglobulin receptor, B and T lymphocyte associated (BTLA),
      permanently prevented GVHD when administered at the time of aHSCT. Once GVHD was
      established, anti-BTLA treatment was unable to reverse disease, suggesting that
      its mechanism occurs early after aHSCT. Anti-BTLA treatment prevented GVHD
      independently of its ligand, the costimulatory tumor necrosis factor receptor
      herpesvirus entry mediator (HVEM), and required BTLA expression by donor-derived
      T cells. Furthermore, anti-BTLA treatment led to the relative inhibition of
      CD4(+) forkhead box P3(-) (Foxp3(-)) effector T cell (T eff cell) expansion
      compared with precommitted naturally occurring donor-derived CD4(+) Foxp3(+)
      regulatory T cell (T reg cell) and allowed for graft-versus-tumor (GVT) effects
      as well as robust responses to pathogens. These results suggest that BTLA agonism
      rebalances T cell expansion in lymphopenic hosts after aHSCT, thereby preventing
      GVHD without global immunosuppression. Thus, targeting BTLA with a monoclonal
      antibody at the initiation of aHSCT therapy might reduce limitations imposed by
      histocompatibility and allow broader application to treatment of non-life
      threatening diseases.

PMID- 21078890
TI  - Development of self-reactive germinal center B cells and plasma cells in
      autoimmune Fc gammaRIIB-deficient mice.
AB  - Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB
      (FcgammaRIIB) are associated with the development of immunoglobulin (Ig) G serum
      autoantibodies and systemic autoimmunity in mice and humans. We used Ig gene
      cloning from single isolated B cells to examine the checkpoints that regulate
      development of autoreactive germinal center (GC) B cells and plasma cells in
      FcgammaRIIB-deficient mice. We found that loss of FcgammaRIIB was associated with
      an increase in poly- and autoreactive IgG(+) GC B cells, including hallmark anti
      nuclear antibody-expressing cells that possess characteristic Ig gene features
      and cells producing kidney-reactive autoantibodies. In the absence of
      FcgammaRIIB, autoreactive B cells actively participated in GC reactions and
      somatic mutations contributed to the generation of highly autoreactive IgG
      antibodies. In contrast, the frequency of autoreactive IgG(+) B cells was much
      lower in spleen and bone marrow plasma cells, suggesting the existence of an
      FcgammaRIIB-independent checkpoint for autoreactivity between the GC and the
      plasma cell compartment.

PMID- 21078891
TI  - Investigating the reliability and validity of the waterlow risk assessment scale:
      a literature review.
AB  - The aim of this review was to examine health literature on the reliability and
      validity of the Waterlow pressure sore assessment scale. A systematic review of
      published studies relating to the topic was conducted and literature was examined
      for its relevancy to the topic under investigation. Findings suggest that despite
      the availability of over 40 assessment tools, the Waterlow assessment scale is
      the most frequently used by health care staff. Research suggests that the
      Waterlow Scale is an unreliable method of assessing individuals at risk of
      pressure sore development with all studies indicating a poor interrater
      reliability status. Its validity has also been criticized because of its high
      sensitivity but low-specificity levels.

PMID- 21078893
TI  - When giving feels good. The intrinsic benefits of sacrifice in romantic
      relationships for the communally motivated.
AB  - Who benefits most from making sacrifices for others? The current study provides
      one answer to this question by demonstrating the intrinsic benefits of sacrifice
      for people who are highly motivated to respond to a specific romantic partner's
      needs noncontingently, a phenomenon termed communal strength. In a 14-day daily
      experience study of 69 romantic couples, communal strength was positively
      associated with positive emotions during the sacrifice itself, with feeling
      appreciated by the partner for the sacrifice, and with feelings of relationship
      satisfaction on the day of the sacrifice. Furthermore, feelings of authenticity
      for the sacrifice mediated these associations. Several alternative hypotheses
      were ruled out: The effects were not due to individuals higher in communal
      strength making qualitatively different kinds of sacrifices, being more positive
      in general, or being involved in happier relationships. Implications for research
      and theory on communal relationships and positive emotions are discussed.

PMID- 21078892
TI  - Proteomics and transcriptomics characterization of bile stress response in
      probiotic Lactobacillus rhamnosus GG.
AB  - Lactobacillus rhamnosus GG (GG) is a widely used and intensively studied
      probiotic bacterium. Although the health benefits of strain GG are well
      documented, the systematic exploration of mechanisms by which this strain exerts
      probiotic effects in the host has only recently been initiated. The ability to
      survive the harsh conditions of the gastrointestinal tract, including gastric
      juice containing bile salts, is one of the vital characteristics that enables a
      probiotic bacterium to transiently colonize the host. Here we used gene
      expression profiling at the transcriptome and proteome levels to investigate the
      cellular response of strain GG toward bile under defined bioreactor conditions.
      The analyses revealed that in response to growth of strain GG in the presence of
      0.2% ox gall the transcript levels of 316 genes changed significantly (p < 0.01,
      t test), and 42 proteins, including both intracellular and surface-exposed
      proteins (i.e. surfome), were differentially abundant (p < 0.01, t test in total
      proteome analysis; p < 0.05, t test in surfome analysis). Protein abundance
      changes correlated with transcriptome level changes for 14 of these proteins. The
      identified proteins suggest diverse and specific changes in general stress
      responses as well as in cell envelope-related functions, including in pathways
      affecting fatty acid composition, cell surface charge, and thickness of the
      exopolysaccharide layer. These changes are likely to strengthen the cell envelope
      against bile-induced stress and signal the GG cells of gut entrance. Notably, the
      surfome analyses demonstrated significant reduction in the abundance of a protein
      catalyzing the synthesis of exopolysaccharides, whereas a protein dedicated for
      active removal of bile compounds from the cells was up-regulated. These findings
      suggest a role for these proteins in facilitating the well founded interaction of
      strain GG with the host mucus in the presence of sublethal doses of bile. The
      significance of these findings in terms of the functionality of a probiotic
      bacterium is discussed.

PMID- 21078894
TI  - Gradual remapping results in early retinotopic and late spatiotopic inhibition of
      return.
AB  - Here we report that immediately following the execution of an eye movement,
      oculomotor inhibition of return resides in retinotopic (eye-centered)
      coordinates. At longer postsaccadic intervals, inhibition resides in spatiotopic
      (world-centered) coordinates. These results are explained in terms of
      perisaccadic remapping. In the interval surrounding an eye movement, information
      is remapped within retinotopic maps to compensate for the retinal displacement.
      Because remapping is not an instantaneous process, a fast, but gradual, transfer
      of inhibition of return from retinotopic to spatiotopic coordinates can be
      observed in the postsaccadic interval. The observation that visual stability is
      preserved in inhibition of return is consistent with its function as a "foraging
      facilitator," which requires locations to be inhibited across multiple eye
      movements. The current results support the idea that the visual system is
      retinotopically organized and that the appearance of a spatiotopic organization
      is due to remapping of visual information to compensate for eye movements.

PMID- 21078895
TI  - The wolfpack effect. Perception of animacy irresistibly influences interactive
      behavior.
AB  - Imagine a pack of predators stalking their prey. The predators may not always
      move directly toward their target (e.g., when circling around it), but they may
      be consistently facing toward it. The human visual system appears to be extremely
      sensitive to such situations, even in displays involving simple shapes. We
      demonstrate this by introducing the wolfpack effect, which is found when several
      randomly moving, oriented shapes (darts, or discs with "eyes") consistently point
      toward a moving disc. Despite the randomness of the shapes' movement, they seem
      to interact with the disc--as if they are collectively pursuing it. This impairs
      performance in interactive tasks (including detection of actual pursuit), and
      observers selectively avoid such shapes when moving a disc through the display
      themselves. These and other results reveal that the wolfpack effect is a novel
      "social" cue to perceived animacy. And, whereas previous work has focused on the
      causes of perceived animacy, these results demonstrate its effects, showing how
      it irresistibly and implicitly shapes visual performance and interactive
      behavior.

PMID- 21078896
TI  - "You talkin' to me?" Self-relevant auditory signals influence perception of gaze
      direction.
AB  - In humans, direct gaze typically signals a deliberate attempt to communicate with
      an observer. An auditory signal with similar signal value is calling someone's
      name. We investigated whether the presence of this personally relevant signal in
      the auditory modality would influence perception of another individual's gaze.
      Participants viewed neutral faces displaying different gaze deviations while
      hearing someone call their own name or the name of another person. Results were
      consistent with our predictions, as participants judged faces with a wider range
      of gaze deviations as looking directly at them when they simultaneously heard
      their own name. The influence of this personally relevant signal was present only
      at ambiguous gaze deviations; thus, an overall response bias to categorize gaze
      as direct when hearing one's own name cannot account for the results. This study
      provides the first evidence that communicative intent signaled via the auditory
      modality influences the perception of another individual's gaze.

PMID- 21078898
TI  - Personality neglect. The unforeseen impact of personal dispositions on emotional
      life.
AB  - The present research provides the first evidence that people neglect their own
      personalities when they envision their future emotional lives. In Study 1,
      students ignored the impact of their dispositional happiness in predicting how
      they would feel 2 weeks after receiving grades. Yet dispositional happiness
      played an important role in shaping actual emotional experiences. Similarly,
      exhibiting personality neglect, participants in Study 2 overlooked their trait
      levels of neuroticism and optimism when forecasting their reaction to Barack
      Obama's election, though these personality dimensions were related to their
      actual emotional reactions. Because they overlooked the influence of their own
      dispositions, individuals incorrectly predicted their future feelings.
      Ironically, as a result of this personality neglect, more optimistic individuals
      were less likely to see their emotional future in an overly rosy light, whereas
      more neurotic individuals were more likely to overestimate the pleasure that the
      future would bring.

PMID- 21078897
TI  - The challenging pupil in the classroom: the effect of the child on the teacher.
AB  - Teaching children requires effort, and some children naturally require more
      effort than others. In this study, we tested whether teacher effort devoted to
      individual children varies as a function of each child's personal
      characteristics. In a nationwide longitudinal study of 1,102 pairs of twins
      followed for 7 years, between the ages of 5 and 12 years, we asked teachers about
      the effort they invested in each child in our study. We found that teacher effort
      was a function of heritable child characteristics, that a child's challenging
      behavior assessed at 5 years of age predicted teacher effort toward the same
      child at 12 years of age, and that challenging child behavior and teacher effort
      share a common etiology with respect to children's genes. We found that child
      effects accounted for a significant proportion of variance in teacher effort, but
      also observed variation in effort exerted by teachers that could not be
      attributed to children's behavior. Treating children who exhibit challenging
      behavior and enhancing teachers' skills in managing such behavior could increase
      the time and energy teachers have to deliver their curriculum in class.

PMID- 21078899
TI  - Induction, overhypothesis, and the origin of abstract knowledge. Evidence from 9
      month-old infants.
AB  - Human cognition relies on the ability to extract generalizable knowledge from
      limited evidence. One type of inductive learning, overhypothesis formation,
      allows learners to make inferences that take them beyond the limits of direct
      experience, leading to the creation of abstract knowledge. The developmental
      roots of this ability have yet to be investigated. We report three experiments
      examining whether 9-month-old infants are capable of forming overhypotheses. Our
      results show that when given evidence about a few objects in some category,
      infants formed a second-order generalization about categories in general. These
      findings provide evidence that infants possess a powerful mechanism for inductive
      learning-a mechanism that may be applied to many domains and that can account for
      the development of many inductive biases later on.

PMID- 21078900
TI  - Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by
      cross-linking of CD70 is dependent upon generation of reactive oxygen species and
      activation of p38 MAPK and JNK pathway.
AB  - CD70 is expressed in normal activated immune cells as well as in several types of
      tumors. It has been established that anti-CD70 mAb induces complement-dependent
      death of CD70(+) tumor cells, but how anti-CD70 mAb affects the intrinsic
      signaling is poorly defined. In this report, we show that ligation of CD70
      expressed on EBV-transformed B cells using anti-CD70 mAb induced production of
      reactive oxygen species (ROS) and subsequent apoptosis. We observed an early
      expression of endoplasmic reticulum (ER) stress response genes that preceded the
      release of apoptotic molecules from the mitochondria and the cleavage of
      caspases. CD70-induced apoptosis was inhibited by pretreatment with the ER stress
      inhibitor salubrinal, ROS quencher N-acetylcysteine, and Ca(2+) chelator BAPTA.
      We supposed that ROS generation might be the first event of CD70-induced
      apoptosis because N-acetylcysteine blocked increases of ROS and Ca(2+), but BAPTA
      did not block ROS generation. We also found that CD70 stimulation activated JNK
      and p38 MAPK. JNK inhibitor SP600125 and p38 inhibitor SB203580 effectively
      blocked upregulation of ER stress-related genes and cleavage of caspases.
      Inhibition of ROS generation completely blocked phosphorylation of JNK and p38
      MAPK and induction of ER stress-related genes. Taken together, we concluded that
      cross-linking of CD70 on EBV-transformed B cells triggered ER stress-mediated
      apoptosis via ROS generation and JNK and p38 MAPK pathway activation. Our report
      reveals alternate mechanisms of direct apoptosis through CD70 signaling and
      provides data supporting CD70 as a viable target for an Ab-based therapy against
      EBV-related tumors.

PMID- 21078901
TI  - TLR ligation triggers somatic hypermutation in transitional B cells inducing the
      generation of IgM memory B cells.
AB  - TLR9 activation by unmethylated CpG provides a homeostatic mechanism to maintain
      B cell memory in the absence of Ag. In this study, we demonstrate that CpG also
      triggers the generation of somatically mutated memory B cells from immature
      transitional B cells. In response to CpG, a fraction of transitional B cells
      proliferates and introduces somatic hypermutations in the H chain V regions. The
      nonproliferating pool of transitional B cells mostly maintains germline
      configurations. Mutations are VH specific: VH5 is the least mutated family,
      whereas VH1 and VH4/6 are the most mutated families. CpG stimulation also results
      in upregulation of VH5 transcripts in proliferating cells. Therefore, early
      recognition of bacterial DNA preferentially expands VH5-expressing B cells while
      inducing somatic hypermutations in other families. The mutation frequency, range,
      and type of substitutions observed in vitro are comparable to those found in
      memory B cells from the peripheral blood of Hyper IgM type 1 patients and the
      spleen of normal infants. The process triggered by TLRs may represent a first
      step leading to additional diversification of the germline repertoire and to the
      generation of memory B cells that will further refine their repertoire and
      specificity in the germinal centers.

PMID- 21078902
TI  - Cutting edge: Hierarchy of maturity of murine memory B cell subsets.
AB  - The paucity of murine memory B cell markers has been a significant impediment to
      the study of memory. The most commonly used marker is IgG, which is neither
      sensitive nor specific, because activated nonmemory cells can be IgG(+), and
      memory cells can be IgM(+). In this article, we show that, together, PD-L2
      (CD273), CD80, and CD73 define at least five phenotypic subsets of murine memory
      B cells. These subsets are generated from naive cells bearing a single BCR in
      response to a single T-dependent Ag. This diversity is independent of class
      switch, because IgG(1)- and IgM-bearing memory cells are found within each
      compartment. Memory subsets defined by PD-L2, CD80, and CD73 are biologically
      distinct from one another, because they differ in ontogeny and selection.
      Together, these distinctions suggest that there is a spectrum of memory B cells
      and progressive acquisition from more naive-like to more memory-like properties.

PMID- 21078903
TI  - Ultraviolet irradiation of mice reduces the competency of bone marrow-derived
      CD11c+ cells via an indomethacin-inhibitable pathway.
AB  - Direct UV irradiation of dendritic cells and Langerhans cells reduces their Ag
      presenting ability. However, the effects of UV on CD11c(+) cells located distally
      to the point of irradiation are poorly understood. Three days after UV
      irradiation (8 kJ/m(2)) of BALB/c mice, bone marrow cells were isolated and
      cultured for 7 d with IL-4 and GM-CSF for the propagation of CD11c(+) cells. Bone
      marrow-derived CD11c(+) cells from UV-irradiated or nonirradiated mice were
      loaded with dinitrobenzene sulfonic acid and injected into the ear pinnas of
      naive BALB/c mice. After 7 d, the ears were painted with 2,4-dinitro-1
      fluorobenzene and the ear swelling determined 24 h later. A reduced contact
      hypersensitivity response was found in mice injected with CD11c(+) cells from the
      UV-irradiated animals compared with those injected with cells from the
      nonirradiated animals. Further, a long-lasting suppression of the memory response
      to 2,4-dinitro-1-fluorobenzene was created. This suppressed response corresponded
      to increased IL-10 and PGE(2) secretion by freshly isolated bone marrow cells
      from UV-irradiated mice, and to increased myelopoiesis. The reduction in
      competence of bone marrow-derived CD11c(+) cells from UV-irradiated mice was not
      due to delayed maturation, as it was maintained upon LPS exposure prior to
      CD11c(+) cell purification. The UV-induced effect was reversed by the
      administration of indomethacin to mice prior to UV irradiation and could be
      reproduced by s.c. PGE(2). These results show that UV irradiation of mice can
      affect the function of bone marrow-derived CD11c(+) cells via a mechanism
      inhibitable by indomethacin; this pathway is likely to contribute to systemic UV
      induced immunosuppression.

PMID- 21078904
TI  - Chondroitin sulfate A-adhering Plasmodium falciparum-infected erythrocytes
      express functionally important antibody epitopes shared by multiple variants.
AB  - Acquired protection from Plasmodium falciparum placental malaria, a major cause
      of maternal, fetal, and infant morbidity, is mediated by IgG specific for the P.
      falciparum erythrocyte membrane protein 1 variant VAR2CSA. This protein enables
      adhesion of P. falciparum-infected erythrocytes to chondroitin sulfate A in the
      intervillous space. Although interclonal variation of the var2csa gene is lower
      than that among var genes in general, VAR2CSA-specific Abs appear to target
      mainly polymorphic epitopes. This has raised doubts about the feasibility of
      VAR2CSA-based vaccines. We used eight human monoclonal IgG Abs from affinity
      matured memory B cells of P. falciparum-exposed women to study interclonal
      variation and functional importance of Ab epitopes among placental and peripheral
      parasites from East and West Africa. Most placental P. falciparum isolates were
      labeled by several mAbs, whereas peripheral isolates from children were
      essentially nonreactive. The mAb reactivity of peripheral isolates from pregnant
      women indicated that some were placental, whereas others had alternative
      sequestration foci. Most of the mAbs were comparable in their reactivity with
      bound infected erythrocytes (IEs) and recombinant VAR2CSA and interfered with IE
      and/or VAR2CSA binding to chondroitin sulfate A. Pair-wise mAb combinations were
      more inhibitory than single mAbs, and all of the mAbs together was the most
      efficient combination. Each mAb could opsonize IEs for phagocytosis, and a
      combination of the eight mAbs caused phagocytosis similar to that of plasma IgG
      opsonized IEs. We conclude that functionally important Ab epitopes are shared by
      the majority of polymorphic VAR2CSA variants, which supports the feasibility of
      VAR2CSA-based vaccines against placental malaria.

PMID- 21078905
TI  - Effector function-deficient memory CD8+ T cells clonally expand in the liver and
      give rise to peripheral memory CD8+ T cells.
AB  - Upon adoptive transfer into histocompatible mice, naive CD8(+) T cells stimulated
      ex vivo by TCR+IL-4 turn into long-lived functional memory cells. The liver
      contains a large number of so formed memory CD8(+) T cells, referred to as liver
      memory T cells (T(lm)) in the form of cell clusters. The CD62L(low) expression
      and nonlymphoid tissue distribution of T(lm) cells are similar to effector memory
      (T(em)) cells, yet their deficient cytotoxicity and IFN-gamma inducibility are
      unlike T(em) cells. Adoptive transfer of admixtures of TCR+IL-4-activated
      Vbeta8(+) and Vbeta5(+) CD8(+) T cells into congenic hosts reveals T(lm) clusters
      that are composed of all Vbeta5(+) or Vbeta8(+), not mixed Vbeta5(+)/Vbeta8(+)
      cells, indicating that T(lm) clusters are formed by clonal expansion. Clonally
      expanded CD8(+) T cell clusters are also seen in the liver of Listeria
      monocytogenes-immune mice. T(lm) clusters closely associate with hepatic stellate
      cells and their formation is IL-15/IL-15R-dependent. CD62L(low) T(LM) cells can
      home to the liver and secondary lymphoid tissues, remain CD62L(low), or acquire
      central memory (T(cm))-characteristic CD62L(hi) expression. Our findings show the
      liver as a major site of CD8(+) memory T cell growth and that T(lm) cells
      contribute to the pool of peripheral memory cells. These previously unappreciated
      T(lm) characteristics indicate the inadequacy of the current T(em)/T(cm)
      classification scheme and help ongoing efforts aimed at establishing a unifying
      memory T cell development pathway. Lastly, our finding of T(lm) clusters suggests
      caution against interpreting focal lymphocyte infiltration in clinical settings
      as pathology and not normal physiology.

PMID- 21078907
TI  - Downstream of tyrosine kinase 1 and 2 play opposing roles in CD200 receptor
      signaling.
AB  - The CD200 receptor (CD200R) negatively regulates myeloid cells by interacting
      with its widely expressed ligand CD200. CD200R signals through a unique
      inhibitory pathway involving a direct interaction with the adaptor protein
      downstream of tyrosine kinase 2 (Dok2) and the subsequent recruitment and
      activation of Ras GTPase-activating protein (RasGAP). Ligand engagement of CD200R
      also results in tyrosine phosphorylation of Dok1, but this protein is not
      essential for inhibitory CD200R signaling in human myeloid cells. In this paper,
      we show that CD200R-induced phosphorylation of Dok2 precedes phosphorylation of
      Dok1, and that Dok2 and Dok1 recruit different downstream proteins. Compared with
      Dok2, Dok1 recruits substantially less RasGAP. In addition to binding RasGAP,
      Dok2 recruits the adaptor molecule Nck in response to ligand engagement of
      CD200R. CD200R-induced phosphorylation of Dok1 results in the recruitment of CT10
      sarcoma oncogene cellular homologue-like (CrkL), whereas the closely related CT10
      sarcoma oncogene cellular homologue interacts constitutively with Dok1. Knockdown
      of Dok1 or CrkL expression in U937 cells resulted in increased Dok2
      phosphorylation and RasGAP recruitment to Dok2. These data are consistent with a
      model in which Dok1 negatively regulates Dok2-mediated CD200R signaling through
      the recruitment of CrkL.

PMID- 21078906
TI  - Inhibition of TLR4-induced IkappaB kinase activity by the RON receptor tyrosine
      kinase and its ligand, macrophage-stimulating protein.
AB  - The RON receptor tyrosine kinase regulates the balance between classical (M1) and
      alternative (M2) macrophage activation. In primary macrophages, the ligand for
      Ron, macrophage-stimulating protein (MSP), inhibits the expression of inducible
      NO synthase, a marker of classically activated macrophages, whereas promoting the
      expression of arginase I, a marker of alternative activation. Ron(-/-) mice
      express increased levels of IL-12, a product of classically activated
      macrophages, after endotoxin administration, resulting in increased serum IFN
      gamma levels and enhanced susceptibility to septic shock. In this study, we
      demonstrate that MSP inhibits LPS-induced IL-12p40 expression, and this
      inhibition is dependent on the docking site tyrosines in Ron. To further define
      this inhibition, we examined the effect of Ron on signaling pathways downstream
      of Ron. We found that MSP does not inhibit the MyD88-independent activation of
      IFN regulatory factor 3 and production of IFN-beta in response to LPS, nor does
      it inhibit MyD88-dependent TGF-beta-activated kinase phosphorylation or MAPK
      activation in primary macrophages. However, the induction of IkappaB kinase
      activity, IkappaB degradation, and DNA binding of NF-kappaB after LPS stimulation
      is delayed in the presence of MSP. In addition, Ron inhibits serine
      phosphorylation of p65 and NF-kappaB transcriptional activity induced by LPS
      stimulation of TLR4. Finally, MSP inhibits the NF-kappaB-dependent upregulation
      of the nuclear IkappaB family member, IkappaBzeta, a positive regulator of
      secondary response genes including IL-12p40. LPS also induces expression of Ron
      and an N-terminally truncated form of Ron, Sf-Ron, in primary macrophages,
      suggesting that the upregulation of Ron by LPS could provide classical feedback
      regulation of TLR signaling.

PMID- 21078908
TI  - The chemorepellent Slit3 promotes monocyte migration.
AB  - Directional migration is an essential step for monocytes to infiltrate sites of
      inflammation, a process primarily regulated by chemoattractants. Slits are large
      matrix proteins that are secreted by endothelial cells; they were reported to
      inhibit the chemoattractant-induced migration of different cell types, including
      leukocytes. The aim of this study was to determine the effect of Slit3 on primary
      monocyte migration and to address the underlying mechanisms. We show that
      Roundabout (Robo)1, one of the Robo receptors that recognize Slit3, is the only
      Robo homolog expressed by CD14(+) monocytes. Interestingly, we found that
      stimulation with Slit3 increased the spontaneous and chemoattractant-induced
      migration of primary monocytes in vitro and increased the myeloid cell
      recruitment during peritoneal inflammation in vivo. In addition, Slit3 did not
      seem to act as a chemoattractant itself; it promoted directed migration triggered
      by chemoattractants, such as CXCL12, by inducing a chemokinetic effect. We
      further show that Slit3 prevented monocyte spreading and induced rounding of
      spread monocytes without affecting monocyte adhesion. Stimulation with Slit3 was
      not associated with changes in the levels of phosphorylated p38, p42/p44, or Src,
      known regulators of monocyte migration, but it directly acts on molecular
      pathways involved in basal leukocyte migration by activating RhoA. These findings
      show an unexpected response of monocytes to Slit3 and add insights into the
      possible role of Slit proteins during inflammatory cell recruitment.

PMID- 21078909
TI  - Fine tuning of the threshold of T cell selection by the Nck adapters.
AB  - Thymic selection shapes the T cell repertoire to ensure maximal antigenic
      coverage against pathogens while preventing autoimmunity. Recognition of self
      peptides in the context of peptide-MHC complexes by the TCR is central to this
      process, which remains partially understood at the molecular level. In this study
      we provide genetic evidence that the Nck adapter proteins are essential for
      thymic selection. In vivo Nck deletion resulted in a reduction of the thymic
      cellularity, defective positive selection of low-avidity T cells, and impaired
      deletion of thymocytes engaged by low-potency stimuli. Nck-deficient thymocytes
      were characterized by reduced ERK activation, particularly pronounced in mature
      single positive thymocytes. Taken together, our findings identify a crucial role
      for the Nck adapters in enhancing TCR signal strength, thereby fine-tuning the
      threshold of thymocyte selection and shaping the preimmune T cell repertoire.

PMID- 21078911
TI  - Inflammatory blood monocytes contribute to tumor development and represent a
      privileged target to improve host immunosurveillance.
AB  - Progressing tumors in humans and mice are frequently infiltrated by a highly
      heterogeneous population of inflammatory myeloid cells that contribute to tumor
      growth. Among these cells, inflammatory Gr-1(+) monocytes display a high
      developmental plasticity in response to specific microenvironmental signals,
      leading to diverse immune functions. These observations raise the question of the
      immune mechanisms by which inflammatory monocytes may contribute to tumor
      development. In this study, we found that adoptive transfer of normal
      inflammatory Gr-1(+) monocytes in tumor-bearing mice promotes tumor growth. In
      this tumoral environment, these monocytes can differentiate into tolerogenic
      dendritic cells (DCs) that produce IL-10 and potently induce regulatory T cell
      responses in vivo. Moreover, diverting the differentiation of Gr-1(+) monocytes
      into tolerogenic DCs by forced expression of IL-10 soluble receptor and IL-3 in
      tumor cells improves host immunosurveillance by reducing the regulatory T cell
      frequency and by inducing immunogenic DCs in the tumor. As a consequence, tumor
      growth is strongly reduced. Our findings indicate that Gr-1(+) monocytes
      represent a valuable target for innovative immunotherapeutic strategies against
      cancer.

PMID- 21078910
TI  - Leptin modulates the survival of autoreactive CD4+ T cells through the
      nutrient/energy-sensing mammalian target of rapamycin signaling pathway.
AB  - Chronic inflammation can associate with autoreactive immune responses, including
      CD4(+) T cell responses to self-Ags. In this paper, we show that the adipocyte
      derived proinflammatory hormone leptin can affect the survival and proliferation
      of autoreactive CD4(+) T cells in experimental autoimmune encephalomyelitis, an
      animal model of human multiple sclerosis. We found that myelin olygodendrocyte
      glycoprotein peptide 35-55 (MOG(35-55))-specific CD4(+) T cells from C57BL/6J
      wild-type mice could not transfer experimental autoimmune encephalomyelitis into
      leptin-deficient ob/ob mice. Such a finding was associated with a reduced
      proliferation of the transferred MOG(35-55)-reactive CD4(+) T cells, which had a
      reduced degradation of the cyclin-dependent kinase inhibitor p27(kip1) and ERK1/2
      phosphorylation. The transferred cells displayed reduced Th1/Th17 responses and
      reduced delayed-type hypersensitivity. Moreover, MOG(35-55)-reactive CD4(+) T
      cells in ob/ob mice underwent apoptosis that associated with a downmodulation of
      Bcl-2. Similar results were observed in transgenic AND-TCR- mice carrying a TCR
      specific for the pigeon cytochrome c 88-104 peptide. These molecular events
      reveal a reduced activity of the nutrient/energy-sensing AKT/mammalian target of
      rapamycin pathway, which can be restored in vivo by exogenous leptin replacement.
      These results may help to explain a link between chronic inflammation and
      autoimmune T cell reactivity.

PMID- 21078912
TI  - Occupancy of lymphocyte LFA-1 by surface-immobilized ICAM-1 is critical for TCR-
      but not for chemokine-triggered LFA-1 conversion to an open headpiece high
      affinity state.
AB  - Lymphocyte arrest and spreading on ICAM-1-expressing APCs require activation of
      lymphocyte LFA-1 by TCR signals, but the conformational switches of this integrin
      during these critical processes are still elusive. Using Ab probes that
      distinguish between different LFA-1 conformations, we found that, unlike strong
      chemokine signals, potent TCR stimuli were insufficient to trigger LFA-1
      extension or headpiece opening in primary human lymphocytes. Nevertheless, LFA-1
      in these TCR-stimulated T cells became highly adhesive to both anchored and
      mobile surface-bound ICAM-1, although it failed to bind soluble ICAM-1 with
      measurable affinity. Rapid rearrangement of LFA-1 by immobilized ICAM-1 switched
      the integrin to an open headpiece conformation within numerous scattered
      submicron focal dots that did not readily collapse into a peripheral LFA-1 ring.
      Headpiece-activated LFA-1 microclusters were enriched with talin but were devoid
      of TCR and CD45. Notably, LFA-1 activation by TCR signals as well as subsequent T
      cell spreading on ICAM-1 took place independently of cytosolic Ca(2+). In
      contrast to LFA-1-activating chemokine signals, TCR activation of LFA-1 readily
      took place in the absence of external shear forces. LFA-1 activation by TCR
      signals also did not require internal myosin II forces but depended on intact
      actin cytoskeleton. Our results suggest that potent TCR signals fail to trigger
      LFA-1 headpiece activation unless the integrin first gets stabilized by surface
      bound ICAM-1 within evenly scattered actin-dependent LFA-1 focal dots, the
      quantal units of TCR-stimulated T cell arrest and spreading on ICAM-1.

PMID- 21078913
TI  - On/off TLR signaling decides proinflammatory or tolerogenic dendritic cell
      maturation upon CD1d-mediated interaction with invariant NKT cells.
AB  - Invariant NKT (iNKT) cells play an effector/adjuvant function during
      antimicrobial and antitumoral immunity and a regulatory role to induce immune
      tolerance and prevent autoimmunity. iNKT cells that differentially modulate
      adaptive immunity do not bear a unique phenotype and/or specific cytokine
      secretion profile, thus opening questions on how a single T cell subset can exert
      opposite immunological tasks. In this study, we show that iNKT cells perform
      their dual roles through a single mechanism of action relying on the cognate
      interaction with myeloid dendritic cells (DCs) and leading to opposite effects
      depending on the presence of other maturation stimuli simultaneously acting on
      DCs. The contact of murine purified iNKT cells with immature autologous DCs
      directly triggers the tolerogenic maturation of DCs, rendering them able to
      induce regulatory T cell differentiation and prevent autoimmune diabetes in vivo.
      Conversely, the interaction of the same purified iNKT cells with DCs, in the
      presence of simultaneous TLR4 stimulation, significantly enhances proinflammatory
      DC maturation and IL-12 secretion. The different iNKT cell effects are mediated
      through distinct mechanisms and activation of different molecular pathways within
      the DC: CD1d signaling and activation of the ERK1/2 pathway for the tolerogenic
      action, and CD40-CD40L interaction and NF-kappaB activation for the adjuvant
      effect. Our data suggest that the DC decision to undergo proinflammatory or
      tolerogenic maturation results from the integration of different signals received
      at the time of iNKT cell contact and could have important therapeutic
      implications for exploiting iNKT cell adjuvant/regulatory properties in
      autoimmune diseases, infections, and cancer.

PMID- 21078914
TI  - Prediction of reactivity to noninherited maternal antigen in MHC-mismatched,
      minor histocompatibility antigen-matched stem cell transplantation in a mouse
      model.
AB  - The immunologic effects of developmental exposure to noninherited maternal Ags
      (NIMAs) are quite variable. Both tolerizing influence and inducing alloreaction
      have been observed on clinical transplantation. The role of minor
      histocompatibility Ags (MiHAs) in NIMA effects is unknown. MiHA is either matched
      or mismatched in NIMA-mismatched transplantation because a donor of the
      transplantation is usually limited to a family member. To exclude the
      participation of MiHA in a NIMA effect for MHC (H-2) is clinically relevant
      because mismatched MiHA may induce severe alloreaction. The aim of this study is
      to understand the mechanism of NIMA effects in MHC-mismatched, MiHA-matched
      hematopoietic stem cell transplantation. Although all offsprings are exposed to
      the maternal Ags, the NIMA effect for the H-2 Ag was not evident. However, they
      exhibit two distinct reactivities, low and high responder, to NIMA in utero and
      during nursing depending on the degree of maternal microchimerism. Low responders
      survived longer with less graft-versus-host disease. These reactivities were
      correlated with Foxp3 expression of peripheral blood CD4(+)CD25(+) cells after
      graft-versus-host disease induction and the number of IFN-gamma-producing cells
      stimulated with NIMA pretransplantation. These observations are clinically
      relevant and suggest that it is possible to predict the immunological tolerance
      to NIMA.

PMID- 21078915
TI  - Online survey of nursing journal peer reviewers: indicators of quality in
      manuscripts.
AB  - Nursing journal peer reviewers (N = 1,675) completed a 69-item online survey that
      assessed their views on manuscripts' contributions to nursing, priorities in
      writing reviews, use of journal impact factor, and other areas related to
      indicators of quality. They reported using contribution to knowledge or research
      evidence, topic of current interest, and newly emerging area as indicators of a
      manuscript's contribution to nursing. In writing their reviews, research rigor
      and clinical relevance of the manuscript were high priorities. Those familiar
      with the concept of impact factor were significantly more often not nurses; not
      United States residents; involved in research; and most often reviewed for
      journals that published only research or a scholarly mix of research, reviews,
      policy, and theory. When judging a paper's contribution, nursing journal peer
      reviewers weigh both research and clinical interests. Most reviewers do not use
      impact factors and place clinical considerations ahead of impact factors.

PMID- 21078916
TI  - Outcomes of a program to reduce depression.
AB  - Depression is increasing among Korean college students. Moreover, it is common
      for depressed individuals to consider attempting suicide. The purpose of this
      study therefore was to develop and examine the effectiveness of an intervention
      to reduce suicidal ideation and depression among female college students. Study
      participants were assigned to either an intervention (n = 27) or control (n = 31)
      group. The intervention group received a depression-reducing program in eight 1
      hr weekly sessions. Measures of suicidal ideation and depression were
      administered. The program has effects on suicidal ideation and depression among
      female college students. The findings suggest that the study program may be
      useful in reducing suicidal ideation and depression among female college
      students.

PMID- 21078918
TI  - Molecular pathogenesis of malignant glial tumors.
AB  - Malignant glial tumors are the most aggressive and difficult to treat neoplasms
      arising in the brain. More than 22,000 people in the United States are diagnosed
      with a malignant glioma annually, and most will die within the first two years
      from diagnosis. Traditionally, gliomas have been categorized based solely on
      tumor histological features. However, expression studies have found that
      molecular signatures can be used to categorize these tumors into subclasses that
      more effectively predict patient outcome. The heterogeneity between tumors as
      well as within individual tumors makes understanding the molecular aspects of
      tumorigenesis extremely important. Several genetically engineered mouse models
      (GEMMs) of glioma have been developed that recapitulate the molecular alterations
      observed in the human disease. GEMMs of glioma have allowed researchers to more
      closely study the role of cancer stem cells (CSC) in gliomagenesis as well as the
      relevance of signaling within the CSC microenvironment. Knowledge of the
      underlying molecular signatures of malignant glial tumors coupled with the
      existence of a variety of human disease-relevant GEMMs of this tumor type provide
      researchers and clinicians with valuable resources for the discovery of new drug
      targets.

PMID- 21078919
TI  - Introduction and commentary: "toxicologic neuropathology"--and a whole lot more!:
      the 2010 joint STP/IFSTP international symposium on toxicologic pathology.

PMID- 21078917
TI  - Consensus statement on standard of care for congenital muscular dystrophies.
AB  - Congenital muscular dystrophies are a group of rare neuromuscular disorders with
      a wide spectrum of clinical phenotypes. Recent advances in understanding the
      molecular pathogenesis of congenital muscular dystrophy have enabled better
      diagnosis. However, medical care for patients with congenital muscular dystrophy
      remains very diverse. Advances in many areas of medical technology have not been
      adopted in clinical practice. The International Standard of Care Committee for
      Congenital Muscular Dystrophy was established to identify current care issues,
      review literature for evidence-based practice, and achieve consensus on care
      recommendations in 7 areas: diagnosis, neurology, pulmonology,
      orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care,
      cardiology, and palliative care. To achieve consensus on the care
      recommendations, 2 separate online surveys were conducted to poll opinions from
      experts in the field and from congenital muscular dystrophy families. The final
      consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in
      November 2009. This consensus statement describes the care recommendations from
      this committee.

PMID- 21078920
TI  - Useful toxicologic neuropathology references for pathologists and toxicologists.
AB  - Investigations in toxicologic neuropathology are complex undertakings because of
      the intricate spatial and temporal diversity in the anatomic, functional, and
      molecular organization of the central and peripheral nervous systems. This
      compilation of toxicologic neuropathology resources has been designed to
      consolidate a broad range of useful neurobiology, neuropathology, and
      neurotoxicology resources in a single reference. This collection will increase
      familiarity with the basic knowledge, skills, and tools required for the
      proficient practice of toxicologic neuropathology and should help to improve the
      analysis and interpretation of pathology data sets from neural tissues in
      toxicology studies.

PMID- 21078921
TI  - Preparation and analysis of the peripheral nervous system.
AB  - This article is from a presentation at the 2010 STP/IFSTP Symposium on
      Neuropathology. The organization and basic structure of the peripheral nervous
      system is reviewed. Examples of toxicant-induced peripheral nerve injury such as
      neuronopathy, axonopathy, and myelinapathy are discussed, as are contemporary
      methods for examination of these tissues.

PMID- 21078922
TI  - Special neuropathology problems.

PMID- 21078923
TI  - Microglia: key innate immune cells of the brain.
AB  - Microglia are the histiocytes of the central nervous system. These long-lived
      cells undergo very little turnover in normal physiological states; however, in
      pathological conditions, increased egress from the bone marrow and
      chemoattractive signals in the brain can substantially modulate the indigenous
      population. Although they were initially conceived of as "resting" cells, recent
      data suggest that they would be more aptly described as "surveillance" cells.
      Microglia are specifically adapted to sense various types of danger and
      differentially react with a classical or alternative reparative response. Our
      understanding of macrophage function has shifted away from focusing on cell
      lineage to a more systems-based biology of gene networks accomplishing the
      detoxification and immune functions. With our greater appreciation of microglial
      involvement in the innate immune response, we have entered a new era in which the
      modulation of microglia can be proposed as a means of modulating neurological
      disease.

PMID- 21078924
TI  - Mechanisms mediating bactericidal properties and conditions that enhance the
      potency of a broad-spectrum oligo-acyl-lysyl.
AB  - Previous studies have established the potential of the oligo-acyl-lysyl (OAK)
      concept in generating simple chemical mimics of host defense peptides (HDPs) with
      improved antimicrobial properties. We investigated the antibacterial properties
      of such an OAK, C(16(omega7))-KK-C(12)-K(amide), to obtain a better understanding
      of the complex mode(s) of action of cationic antibacterial peptides. The average
      MIC, determined against a multispecies panel of 50 strains, was 6 +/- 5 MUg/ml.
      However, although the OAK exerted an essentially dose-dependent bactericidal
      effect (time-kill curves typically exhibited 99% death within 2 h), marked
      differences in the killing rates occurred among inter- and intraspecies strains.
      Mechanistic comparison between equally sensitive and related strains revealed
      death of one strain to stem from the OAK's capacity to breach the cell membrane
      permeability barrier, whereas the death of the related strain resulted from the
      OAK's direct interference with DNA functions in vivo, without detectable membrane
      damage. These findings therefore support the notion that the antibacterial
      mechanism of action of a single HDP can vary among inter- and intraspecies
      strains. In addition, we present data illustrating the differential effects of
      environmental conditions (pH, ionic strength and temperature), on the OAK's
      antibacterial properties, and ultimately demonstrate potency enhancement (by
      orders of magnitude) through selection of optimal incubation conditions. Such
      attributes might be useful in a variety of antibacterial applications.

PMID- 21078925
TI  - Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in
      Papua New Guinea using an extended ligase detection reaction fluorescent
      microsphere assay.
AB  - Surveillance for Plasmodium falciparum drug resistance mutations is becoming an
      established tool for assessing antimalarial treatment effectiveness. We used an
      extended version of a high-throughput post-PCR multiplexed ligase detection
      reaction fluorescent microsphere assay (LDR-FMA) to detect single-nucleotide P.
      falciparum drug resistance polymorphisms in 402 isolates from children in Papua
      New Guinea (PNG) participating in an antimalarial treatment trial. There was a
      fixation of P. falciparum crt (pfcrt) K76T, pfdhfr C59R and S108N, and pfmdr1
      mutations (92%, 93%, 95%, and 91%, respectively). Multiple mutations were
      frequent. Eighty-eight percent of isolates possessed a quintuple mutation
      (underlined), SVMNT, NRNI, KAA, and YYSND, in codons 72 to 76 for pfcrt; 51, 59,
      108, and 164 for pfdhfr; 540, 581, and 613 for pfdhps; and 86, 184, 1034, 1042,
      and 1246 for pfmdr1, and four of these carried the K540E pfdhps allele. The
      pfmdr1 D1246Y mutation was associated with PCR-corrected day 42 in vivo treatment
      failure in children allocated piperaquine-dihydroartemisinin (P = 0.004).
      Although the pfmdr1 NFSDD haplotype was found in only four isolates, it has been
      associated with artemether-lumefantrine treatment failure in Africa. LDR-FMA
      allows the large-scale assessment of resistance-associated single-nucleotide
      polymorphisms (SNPs). Our findings reflect previous heavy 4
      aminoquinoline/sulfadoxine-pyrimethamine use in PNG. Since artemether
      lumefantrine and piperaquine-dihydroartemisinin will become first- and second
      line treatments, respectively, the monitoring of pfmdr1 SNPs appears to be a high
      priority.

PMID- 21078926
TI  - Determination of the duration of antibacterial efficacy following administration
      of gamithromycin using a bovine Mannheimia haemolytica challenge model.
AB  - The antibacterial efficacy of gamithromycin administered once 1, 5, or 10 days
      prior to a challenge infection with Mannheimia haemolytica serotype A1 was
      evaluated. Forty calves were randomly allocated on day -11, restricted by body
      weight, to one of three treatment groups given gamithromycin at 6 mg/kg of body
      weight 10, 5, or 1 days before challenge or to an untreated control group. M.
      haemolytica A1 challenge infections were induced on day 0 by depositing 7.4 *
      10(7) CFU at the bifurcation of the main bronchus using a bronchoscope. Clinical
      observations were made daily from the day of allocation to day 10, when necropsy
      was scheduled; three calves died or were euthanized in extremis on welfare
      grounds prior to scheduled necropsy. At necropsy the lungs were removed,
      pneumonic lesions were scored, and samples of lung tissue were cultured for M.
      haemolytica. The three groups of animals treated with gamithromycin before
      challenge had significantly lower lung M. haemolytica counts and fewer clinical
      signs of respiratory disease than did the saline-treated group. For most of the
      clinical parameters, the pattern of responses differed significantly (P < 0.05)
      between the gamithromycin-treated groups and the control group. There were no
      statistically significant differences between groups in the mean lung lesion
      scores, partly as a result of high individual variability, particularly within
      the control group. The administration of gamithromycin 1, 5, and 10 days prior to
      M. haemolytica A1 challenge resulted in a reduction in bacterial isolation from
      the lungs and a reduction in the severity of clinical disease.

PMID- 21078927
TI  - Peptide antibiotic sensing and detoxification modules of Bacillus subtilis.
AB  - Peptide antibiotics are produced by a wide range of microorganisms. Most of them
      target the cell envelope, often by inhibiting cell wall synthesis. One of the
      resistance mechanisms against antimicrobial peptides is a detoxification module
      consisting of a two-component system and an ABC transporter. Upon the detection
      of such a compound, the two-component system induces the expression of the ABC
      transporter, which in turn removes the antibiotic from its site of action,
      mediating the resistance of the cell. Three such peptide antibiotic-sensing and
      detoxification modules are present in Bacillus subtilis. Here we show that each
      of these modules responds to a number of peptides and confers resistance against
      them. BceRS-BceAB (BceRS-AB) responds to bacitracin, plectasin, mersacidin, and
      actagardine. YxdJK-LM is induced by a cationic antimicrobial peptide, LL-37. The
      PsdRS-AB (formerly YvcPQ-RS) system responds primarily to lipid II-binding
      lantibiotics such as nisin and gallidermin. We characterized the psdRS-AB operon
      and defined the regulatory sequences within the P(psdA) promoter. Mutation
      analysis demonstrated that P(psdA) expression is fully PsdR dependent. The
      features of both the P(bceA) and P(psdA) promoters make them promising candidates
      as novel whole-cell biosensors that can easily be adjusted for high-throughput
      screening.

PMID- 21078928
TI  - mexEF-oprN multidrug efflux operon of Pseudomonas aeruginosa: regulation by the
      MexT activator in response to nitrosative stress and chloramphenicol.
AB  - A null mutation in the mexS gene of Pseudomonas aeruginosa yielded an increased
      level of expression of a 3-gene operon containing a gene, xenB, whose product is
      highly homologous to a xenobiotic reductase in Pseudomonas fluorescens shown
      previously to remove nitro groups from trinitrotoluene and nitroglycerin (D. S.
      Blehert, B. G. Fox, and G. H. Chambliss, J. Bacteriol. 181:6254, 1999). This
      expression, which paralleled an increase in mexEF-oprN expression in the same
      mutant, was, like mexEF-oprN, dependent on the MexT LysR family positive
      regulator previously implicated in mexEF-oprN expression. As nitration is a well
      known result of nitrosative stress, a role for xenB (and the coregulated mexEF
      oprN) in a nitrosative stress response was hypothesized and tested. Using s
      nitrosoglutathione (GSNO) as a source of nitrosative stress, the expression of
      xenB and mexEF-oprN was shown to be GSNO inducible, although in the case of xenB,
      this was seen only for a mutant lacking MexEF-OprN. In both instances, this GSNO
      inducible expression was dependent upon MexT. Chloramphenicol, a nitroaromatic
      antimicrobial that is a substrate for MexEF-OprN, was shown to induce mexEF-oprN
      but not xenB, again dependent upon the MexT regulator, possibly because it
      resembles a nitrosated nitrosative stress product accommodated by MexEF-OprN.

PMID- 21078931
TI  - Human tissue distribution of voriconazole.
AB  - Voriconazole concentrations were determined in autopsy samples of eight patients
      who had been treated for a median of 7 days (interquartile range [IQR], 5 days).
      Voriconazole penetrates well into various tissues, with median levels of 6.26
      MUg/g ((interquartile range [IQR], 7.87 MUg/g) in the lung, 3.41 MUg/g (IQR,
      16.72 MUg/g) in the brain, 6.89 MUg/g (IQR, 24.16 MUg/g) in the liver, 6.47 MUg/g
      (IQR, 6.19 MUg/g) in the kidneys, 5.60 MUg/g (IQR, 11.49 MUg/g) in the spleen,
      and 7.55 MUg/g (IQR, 16.91 MUg/g) in the myocardium.

PMID- 21078930
TI  - High-throughput Giardia lamblia viability assay using bioluminescent ATP content
      measurements.
AB  - The human pathogen Giardia lamblia is an anaerobic protozoan parasite that causes
      giardiasis, one of the most common diarrheal diseases worldwide. Although several
      drugs are available for the treatment of giardiasis, drug resistance has been
      reported and is likely to increase, and recurrent infections are common. The
      search for new drugs that can overcome the drug-resistant strains of Giardia is
      an unmet medical need. New drug screen methods can facilitate the drug discovery
      process and aid with the identification of new drug targets. Using a
      bioluminescent ATP content assay, we have developed a phenotypic drug screen
      method to identify compounds that act against the actively growing trophozoite
      stage of the parasite. This assay is homogeneous, robust, and suitable for high
      throughput screening of large compound collections. A screen of 4,096
      pharmacologically active small molecules and approved drugs revealed 43 compounds
      with selective anti-Giardia properties, including 32 previously reported and 11
      novel anti-Giardia agents. The most potent novel compound was fumagillin, which
      showed 50% inhibitory concentrations of 10 nM against the WB isolate and 2 nM
      against the GS isolate.

PMID- 21078932
TI  - Amiodarone inhibits Trypanosoma cruzi infection and promotes cardiac cell
      recovery with gap junction and cytoskeleton reassembly in vitro.
AB  - We present the results of the first detailed study of the antiproliferative and
      ultrastructural effects of amiodarone on Trypanosoma cruzi, the causative agent
      of Chagas' disease. Moreover, we report the effects of this compound on the
      recovery of F-actin fibrils, connexin43, and contractility in T. cruzi-infected
      cardiac myocytes. Amiodarone is the most prescribed class III antiarrhythmic
      agent and is frequently used for the symptomatic treatment of Chagas' disease
      patients with cardiac compromise. In addition, recent studies identified its
      antifungal and antiprotozoal activities, which take place through Ca(2+)
      homeostasis disruption and ergosterol biosynthesis blockade. We tested different
      concentrations of amiodarone (2.5 to 10 MUM) on infected primary cultures of
      heart muscle cells and observed a dose- and time-dependent effect on growth of
      the clinically relevant intracellular amastigote form of T. cruzi.
      Ultrastructural analyses revealed that amiodarone had a profound effect on
      intracellular amastigotes, including mitochondrial swelling and disorganization
      of reservosomes and the kinetoplast and a blockade of amastigote-trypomastigote
      differentiation. Amiodarone showed no toxic effects on host cells, which
      recovered their F-actin fibrillar organization, connexin43 distribution, and
      spontaneous contractility concomitant with the drug-induced eradication of the
      intracellular parasites. Amiodarone is, therefore, a promising compound for the
      development of new drugs against T. cruzi.

PMID- 21078929
TI  - Resistance of herpes simplex viruses to nucleoside analogues: mechanisms,
      prevalence, and management.
AB  - Herpes simplex viruses (HSV) type 1 and type 2 are responsible for recurrent
      orolabial and genital infections. The standard therapy for the management of HSV
      infections includes acyclovir (ACV) and penciclovir (PCV) with their respective
      prodrugs valacyclovir and famciclovir. These compounds are phosphorylated by the
      viral thymidine kinase (TK) and then by cellular kinases. The triphosphate forms
      selectively inhibit the viral DNA polymerase (DNA pol) activity. Drug-resistant
      HSV isolates are frequently recovered from immunocompromised patients but rarely
      found in immunocompetent subjects. The gold standard phenotypic method for
      evaluating the susceptibility of HSV isolates to antiviral drugs is the plaque
      reduction assay. Plaque autoradiography allows the associated phenotype to be
      distinguished (TK-wild-type, TK-negative, TK-low-producer, or TK-altered viruses
      or mixtures of wild-type and mutant viruses). Genotypic characterization of drug
      resistant isolates can reveal mutations located in the viral TK and/or in the DNA
      pol genes. Recombinant HSV mutants can be generated to analyze the contribution
      of each specific mutation with regard to the drug resistance phenotype. Most ACV
      resistant mutants exhibit some reduction in their capacity to establish latency
      and to reactivate, as well as in their degree of neurovirulence in animal models
      of HSV infection. For instance, TK-negative HSV mutants establish latency with a
      lower efficiency than wild-type strains and reactivate poorly. DNA pol HSV
      mutants exhibit different degrees of attenuation of neurovirulence. The
      management of ACV- or PCV-resistant HSV infections includes the use of the
      pyrophosphate analogue foscarnet and the nucleotide analogue cidofovir. There is
      a need to develop new antiherpetic compounds with different mechanisms of action.

PMID- 21078933
TI  - Pharmacodynamic modeling of in vitro activity of marbofloxacin against
      Escherichia coli strains.
AB  - A mathematical pharmacodynamic model was developed to describe the bactericidal
      activity of marbofloxacin against Escherichia coli strains with reduced
      susceptibility levels (determined using MICs) under optimal and intestinal growth
      conditions. Model parameters were estimated using nonlinear least-square curve
      fitting procedures for each E. coli strain. Parameters related to bactericidal
      activity were subsequently analyzed using a maximum-effect (E(max)) model adapted
      to account for a direct and a delayed effect. While net growth rates did not vary
      significantly with strain susceptibility, culture medium had a major effect. The
      bactericidal activity of marbofloxacin was closely associated with the
      concentration and the duration of exposure of the bacteria to the antimicrobial
      agent. The value of the concentration inducing a half-maximum effect (C(50)) was
      highly correlated with MIC values (R(2) = 0.87 and R(2) = 0.94 under intestinal
      and optimal conditions, respectively). Our model reproduced the time-kill
      kinetics with good accuracy (R(2) of >0.90) and helped explain observed regrowth.

PMID- 21078934
TI  - First molecular characterization of fluoroquinolone resistance in Aerococcus spp.

PMID- 21078935
TI  - rmtD2, a new allele of a 16S rRNA methylase gene, has been present in
      Enterobacteriaceae isolates from Argentina for more than a decade.
AB  - The first allele of a 16S rRNA methyltransferase gene, rmtD2, conferring very
      high resistance to all clinically available aminoglycosides, was detected in
      7/1,064 enterobacteria collected in 2007. rmtD2 was located on a conjugative
      plasmid in a Tn2670-like element inside a structure similar to that of rmtD1 but
      probably having an independent assembly. rmtD2 has been found since 1996 to 1998
      mainly in Enterobacter and Citrobacter isolates, suggesting a possible reservoir
      in these genera. This presumption deserves monitoring by continuous surveillance.

PMID- 21078936
TI  - Raltegravir is a substrate for SLC22A6: a putative mechanism for the interaction
      between raltegravir and tenofovir.
AB  - The identification of transporters of the HIV integrase inhibitor raltegravir
      could be a factor in an understanding of the pharmacokinetic-pharmacodynamic
      relationship and reported drug interactions of raltegravir. Here we determined
      whether raltegravir was a substrate for ABCB1 or the influx transporters SLCO1A2,
      SLCO1B1, SLCO1B3, SLC22A1, SLC22A6, SLC10A1, SLC15A1, and SLC15A2. Raltegravir
      transport by ABCB1 was studied with CEM, CEM(VBL100), and Caco-2 cells. Transport
      by uptake transporters was assessed by using a Xenopus laevis oocyte expression
      system, peripheral blood mononuclear cells, and primary renal cells. The kinetics
      of raltegravir transport and competition between raltegravir and tenofovir were
      also investigated using SLC22A6-expressing oocytes. Raltegravir was confirmed to
      be an ABCB1 substrate in CEM, CEM(VBL100), and Caco-2 cells. Raltegravir was also
      transported by SLC22A6 and SLC15A1 in oocyte expression systems but not by other
      transporters studied. The K(m) and V(max) for SLC22A6 transport were 150 MUM and
      36 pmol/oocyte/h, respectively. Tenofovir and raltegravir competed for SLC22A6
      transport in a concentration-dependent manner. Raltegravir inhibited 1 MUM
      tenofovir with a 50% inhibitory concentration (IC(50)) of 14.0 MUM, and tenofovir
      inhibited 1 MUM raltegravir with an IC(50) of 27.3 MUM. Raltegravir
      concentrations were not altered by transporter inhibitors in peripheral blood
      mononuclear cells or primary renal cells. Raltegravir is a substrate for SLC22A6
      and SLC15A1 in the oocyte expression system. However, transport was limited
      compared to endogenous controls, and these transporters are unlikely to have a
      great impact on raltegravir pharmacokinetics.

PMID- 21078937
TI  - An A643V amino acid substitution in Upc2p contributes to azole resistance in well
      characterized clinical isolates of Candida albicans.
AB  - The Candida albicans Upc2p transcription factor regulates ERG11, encoding the
      target of azole drugs. Gain-of-function mutations that contribute to resistance
      were recently identified in a series of sequential clinical isolates (N. Dunkel,
      T. T. Liu, K. S. Barker, R. Homayouni, J. Morschhauser, and P. D. Rogers,
      Eukaryot. Cell 7:1180-1190, 2008). In the present study, UPC2 was sequenced from
      a matched set of 17 isolates. An A643V substitution was present in all of the
      isolates in the series that overexpressed ERG11. Azole susceptibility, ergosterol
      levels, and expression of ERG genes were elevated in the A643V clinical isolates
      and in reconstructed strains.

PMID- 21078938
TI  - Pre-steady-state kinetic analysis of the incorporation of anti-HIV nucleotide
      analogs catalyzed by human X- and Y-family DNA polymerases.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are an important class of
      antiviral drugs used to manage infections by human immunodeficiency virus, which
      causes AIDS. Unfortunately, these drugs cause unwanted side effects, and the
      molecular basis of NRTI toxicity is not fully understood. Putative routes of NRTI
      toxicity include the inhibition of human nuclear and mitochondrial DNA
      polymerases. A strong correlation between mitochondrial toxicity and NRTI
      incorporation catalyzed by human mitochondrial DNA polymerase has been
      established both in vitro and in vivo. However, it remains to be determined
      whether NRTIs are substrates for the recently discovered human X- and Y-family
      DNA polymerases, which participate in DNA repair and DNA lesion bypass in vivo.
      Using pre-steady-state kinetic techniques, we measured the substrate specificity
      constants for human DNA polymerases beta, lambda, eta, iota, kappa, and Rev1
      incorporating the active, 5'-phosphorylated forms of tenofovir, lamivudine,
      emtricitabine, and zidovudine. For the six enzymes, all of the drug analogs were
      incorporated less efficiently (40- to >110,000-fold) than the corresponding
      natural nucleotides, usually due to a weaker binding affinity and a slower rate
      of incorporation for the incoming nucleotide analog. In general, the 5'
      triphosphate forms of lamivudine and zidovudine were better substrates than
      emtricitabine and tenofovir for the six human enzymes, although the substrate
      specificity profile depended on the DNA polymerase. Our kinetic results suggest
      NRTI insertion catalyzed by human X- and Y-family DNA polymerases is a potential
      mechanism of NRTI drug toxicity, and we have established a structure-function
      relationship for designing improved NRTIs.

PMID- 21078939
TI  - Systematic review and meta-analysis of the significance of heterogeneous
      vancomycin-intermediate Staphylococcus aureus isolates.
AB  - The prevalence of heteroresistant vancomycin-intermediate Staphylococcus aureus
      (hVISA) is 1.3% in published studies. Clinical associations include high-inoculum
      infections and glycopeptide failure, with hVISA infections associated with a 2.37
      times-greater failure rate (95% confidence interval [CI], 1.53 to 3.67) compared
      to vancomycin-sensitive Staphylococcus aureus (VSSA) infections. Despite this, 30
      day mortality rates were similar to those for VSSA infections (odds ratio [OR],
      1.18; 95% CI, 0.81 to 1.74). The optimal therapy for hVISA requires further
      study.

PMID- 21078940
TI  - Using bioluminescence to monitor treatment response in real time in mice with
      Mycobacterium ulcerans infection.
AB  - Mycobacterium ulcerans causes Buruli ulcer, a potentially disabling ulcerative
      skin disease. Only recently was antimicrobial therapy proven effective. Treatment
      for 2 months with rifampin plus streptomycin was first proposed after experiments
      in the mouse footpad model demonstrated bactericidal activity. This treatment is
      now considered the treatment of choice, although larger ulcers may require
      adjunctive surgery. Shorter, oral regimens are desired, but evaluating drug
      activity in mice is hampered by the very slow growth of M. ulcerans, which takes
      3 months to produce countable colonies. We created a recombinant bioluminescent
      M. ulcerans strain expressing luxAB from Vibrio harveyi for real-time evaluation
      of antimicrobial effects in vivo. Mouse footpads were injected with wild-type M.
      ulcerans 1059 (WtMu) or the recombinant bioluminescent strain (rMu). Two weeks
      later, mice received rifampin plus streptomycin, kanamycin alone (to which rMu is
      resistant), or streptomycin alone for 4 weeks and were observed for footpad
      swelling (preventive model). Untreated controls and kanamycin-treated rMu
      infected mice received rifampin plus streptomycin for 4 weeks after developing
      footpad swelling (curative model). Compared to WtMu, rMu exhibited similar growth
      and virulence in vivo and similar drug susceptibility. A good correlation was
      observed between luminescence (measured as relative light units) and number of
      viable bacteria (measured by CFU) in footpad homogenates. Proof of concept was
      also shown for serial real-time evaluation of drug activity in live mice. These
      results indicate the potential of bioluminescence as a real-time surrogate marker
      for viable bacteria in mouse footpads to accelerate the identification of new
      treatments for Buruli ulcer.

PMID- 21078941
TI  - Limited ability of Plasmodium falciparum pfcrt, pfmdr1, and pfnhe1 polymorphisms
      to predict quinine in vitro sensitivity or clinical effectiveness in Uganda.
AB  - Quinine is a standard drug for treating severe malaria in Africa, and it is also
      increasingly used to treat uncomplicated disease. However, failures of quinine
      therapy are common, and it is unknown if failures in Africa are due to drug
      resistance. Recent studies have identified associations between in vitro quinine
      sensitivity and polymorphisms in genes encoding putative transporters, including
      well-described polymorphisms in pfcrt and pfmdr1 and varied numbers of DNNND or
      DDNHNDNHNND repeats in microsatellite 4760 (ms4760) of the predicted sodium
      hydrogen exchanger, pfnhe1. To better characterize mediators of quinine response,
      we assessed associations between genetic polymorphisms, in vitro quinine
      sensitivity, and quinine treatment responses in Kampala, Uganda. Among 172 fresh
      clinical isolates tested in vitro, decreasing sensitivity to quinine was
      associated with accumulation of pfmdr1 mutations at codons 86, 184, and 1246.
      Nearly all parasites had pfcrt 76T, preventing analysis of associations with this
      mutation. pfnhe1 ms4760 was highly polymorphic. Parasites with 2 copies of either
      ms4760 repeat showed modest decreases in quinine sensitivity compared to those
      with 1 or >=3 repeats, but the differences were not statistically significant.
      None of the above polymorphisms predicted treatment failure among 66 subjects
      treated with quinine for uncomplicated malaria. Our data suggest that quinine
      sensitivity is a complex trait and that known polymorphisms in pfcrt, pfmdr1, and
      pfnhe1, while associated with quinine sensitivity, are not robust markers for
      quinine resistance.

PMID- 21078942
TI  - Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV
      infected patients.
AB  - The aim of this open-label, fixed-sequence study was to investigate the potential
      of Echinacea purpurea, a commonly used botanical supplement, to interact with the
      boosted protease inhibitor darunavir-ritonavir. Fifteen HIV-infected patients
      receiving antiretroviral therapy including darunavir-ritonavir (600/100 mg twice
      daily) for at least 4 weeks were included. E. purpurea root extract capsules were
      added to the antiretroviral treatment (500 mg every 6 h) from days 1 to 14.
      Darunavir concentrations in plasma were determined by high-performance liquid
      chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning
      dose of darunavir-ritonavir on days 0 (darunavir-ritonavir) and 14 (darunavir
      ritonavir plus echinacea). Individual darunavir pharmacokinetic parameters were
      calculated by noncompartmental analysis and compared between days 0 and 14 with
      the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median
      age was 49 (range, 43 to 67) years, and the body mass index was 24.2 (range, 18.7
      to 27.5) kg/m(2). Echinacea was well tolerated, and all participants completed
      the study. The GMR for darunavir coadministered with echinacea relative to that
      for darunavir alone was 0.84 (90% CI, 0.63-1.12) for the concentration at the end
      of the dosing interval, 0.90 (90% CI, 0.74-1.10) for the area under the
      concentration-time curve from 0 to 12 h, and 0.98 (90% CI, 0.82-1.16) for the
      maximum concentration. In summary, coadministration of E. purpurea with darunavir
      ritonavir was safe and well tolerated. Individual patients did show a decrease in
      darunavir concentrations, although this did not affect the overall darunavir or
      ritonavir pharmacokinetics. Although no dose adjustment is required, monitoring
      darunavir concentrations on an individual basis may give reassurance in this
      setting.

PMID- 21078943
TI  - Pharmacodynamics of telavancin studied in an in vitro pharmacokinetic model of
      infection.
AB  - The antibacterial effects of telavancin, vancomycin, and teicoplanin against six
      Staphylococcus aureus strains (1 methicillin-susceptible S. aureus [MSSA] strain,
      4 methicillin-resistant S. aureus [MRSA] strains, and 1 vancomycin-intermediate
      S. aureus [VISA] strain) and three Enterococcus sp. strains (1 Enterococcus
      faecalis strain, 1 Enterococcus faecium strain, and 1 vancomycin-resistant E.
      faecium [VREF] strain) were compared using an in vitro pharmacokinetic model of
      infection. Analyzing the data from all five vancomycin-susceptible S. aureus
      (VSSA) strains or all 4 MRSA strains showed that telavancin was superior in its
      antibacterial effect as measured by the area under the bacterial kill curve at 24
      h (AUBKC(24)) and 48 h (AUBKC(48)) in comparison to vancomycin or teicoplanin (P
      < 0.05). Telavancin was also superior to vancomycin and teicoplanin in terms of
      its greater early killing effect (P < 0.05). Against the three Enterococcus spp.
      tested, telavancin was superior to vancomycin in terms of its AUBKC(24),
      AUBKC(48), and greater early bactericidal effect (P < 0.05). Dose-ranging studies
      were performed to provide free-drug area under the concentration-time curve over
      24 h in the steady state divided by the MIC (fAUC/MIC) exposures from 0 to 1,617
      (7 to 14 exposures per strain) for 5 VSSA, 4 VISA, and the 3 Enterococcus
      strains. The fAUC/MIC values for a 24-h bacteriostatic effect and a 1-log-unit
      drop in the viable count were 43.1 +/- 38.4 and 50.0 +/- 39.0 for VSSA, 3.2 +/-
      1.3 and 4.3 +/- 1.3 for VISA, and 15.1 +/- 8.8 and 40.1 +/- 29.4 for the
      Enterococcus spp., respectively. The reason for the paradoxically low fAUC/MIC
      values for VISA strains is unknown. There was emergence of resistance to
      telavancin in the dose-ranging studies, as indicated by subpopulations able to
      grow on plates containing 2* MIC telavancin concentrations compared to the
      preexposure population analysis profiles. Changes in population analysis profiles
      were less likely with enterococci than with S. aureus, and the greatest risk of
      changed profiles occurred for both species at fAUC/MIC ratios of 1 to 10.
      Maintaining a fAUC/MIC ratio of >50 reduced the risk of subpopulations able to
      grow on antibiotic-containing media emerging. These data help explain the
      clinical effectiveness of telavancin against MRSA and indicate that telavancin
      may have clinically useful activity against Enterococcus spp., and perhaps also
      VISA, at human doses of 10 mg/kg of body weight/day. In addition, they support a
      clinical breakpoint of sensitive at <=1 mg/liter for both S. aureus and
      Enterococcus spp.

PMID- 21078944
TI  - Oral hexadecyloxypropyl-cidofovir therapy in pregnant guinea pigs improves
      outcome in the congenital model of cytomegalovirus infection.
AB  - Cytomegalovirus (CMV) infection is the leading cause of congenital infection,
      producing both sensorineural hearing loss and mental retardation. We evaluated
      the in vivo efficacy of an orally bioavailable analog of cidofovir,
      hexadecyloxypropyl-cidofovir (HDP-CDV), against guinea pig CMV (GPCMV) in a
      guinea pig model of congenital CMV infection. HDP-CDV exhibited antiviral
      activity against GPCMV with a 50% effective concentration (EC(50)) of 0.004 MUM
      +/- 0.001 MUM. To evaluate in vivo efficacy, pregnant Hartley guinea pigs were
      inoculated with GPCMV during the late second/early third trimester of gestation.
      Animals were administered 20 mg HDP-CDV/kg body weight orally at 24 h
      postinfection (hpi) and again at 7 days postinfection (dpi) or administered 4
      mg/kg HDP-CDV orally each day for 5 days or 9 days. Virus levels in dam and pup
      tissues were evaluated following delivery, or levels from dam, placenta, and
      fetal tissues were evaluated following sacrifice of dams at 10 dpi. All HDP-CDV
      regimens significantly improved pup survival, from 50 to 60% in control animals
      to 93 to 100% in treated animals (P <= 0.019). Treatment with 20 mg/kg HDP-CDV
      significantly reduced the viral load in pup spleen (P = 0.017) and liver (P =
      0.029). Virus levels in the placenta were significantly reduced at 10 dpi
      following daily treatment with 4 mg/kg HDP-CDV for 5 or 9 days. The 9-day
      treatment also significantly reduced the viral levels in the dam spleen and
      liver. Although the 4-mg/kg treatment improved pup survival, virus levels in the
      fetal tissues were similar to those in control tissues. Taken together, HDP-CDV
      shows potential as a well-tolerated antiviral candidate for treatment of
      congenital human CMV (HCMV) infection.

PMID- 21078945
TI  - Cold shock induces qnrA expression in Shewanella algae.
AB  - Plasmid-carried quinolone resistance genes, like qnrA, are widespread in
      Enterobacteriaceae. To gain insight into its little-understood native functions,
      we studied the effect of environmental conditions on chromosomal qnrA expression
      in Shewanella algae. Among conditions of DNA damage, oxidative and osmotic
      stress, starvation, heat, and cold, only cold shock increased gene expression, as
      measured by quantitative reverse transcription-PCR (qRT-PCR). Induction was
      graded and occurred during growth arrest, suggesting that qnrA may contribute to
      the adaptation of Shewanella to low temperatures.

PMID- 21078947
TI  - High mortality among older patients treated with pentavalent antimonials for
      visceral leishmaniasis in East Africa and rationale for switch to liposomal
      amphotericin B.

PMID- 21078946
TI  - Recent exposure to caspofungin or fluconazole influences the epidemiology of
      candidemia: a prospective multicenter study involving 2,441 patients.
AB  - A prospective multicenter surveillance program on yeast bloodstream infections
      was implemented in the Paris, France, area without restrictions on ward of
      hospitalization (intensive care unit, hematology, and surgery) or age (adults and
      children). The present analysis concerns 2,618 isolates collected over 7 years
      from 2,441 patients. Centralized species identification and antifungal
      susceptibility testing using the EUCAST methodology were performed. Almost 10%
      (232/2,441) of the patients had recently (<=30 days) been treated with antifungal
      drugs. We analyzed the effect of recent exposure to fluconazole (n = 159) or
      caspofungin (n = 61) on the proportions of the five major Candida species. For
      both drugs, preexposure was associated with a decreased prevalence of Candida
      albicans in favor of less drug-susceptible species (C. glabrata and C. krusei for
      the former and C. parapsilosis and, to a lesser extent, C. glabrata and C. krusei
      for the latter; P = 0.001). In the multivariate analysis, the risk of being
      infected with an isolate with decreased susceptibility to fluconazole was
      independently associated with an age of >=15 years (odds ratio [OR] = 2.45; 95%
      confidence interval [CI] = 1.39 to 4.31; P = 0.002) and with recent exposure to
      fluconazole (OR = 2.17; 95% CI = 1.51 to 3.13; P < 0.001), while the risk of
      being infected with an isolate with decreased susceptibility to caspofungin was
      independently associated with an age <15 years (OR = 2.53; 95% CI = 1.43 to 4.48;
      P = 0.001) and with recent exposure to caspofungin (OR = 4.79; 95% CI = 2.47 to
      9.28; P < 0.001). These findings could influence future recommendations for the
      management of candidemia.

PMID- 21078948
TI  - In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043.
AB  - Attachment inhibitors (AI) are a novel class of HIV-1 antivirals, with little
      information available on clinical resistance. BMS-488043 is an orally
      bioavailable AI that binds to gp120 of HIV-1 and abrogates its binding to CD4(+)
      lymphocytes. A clinical proof-of-concept study of the AI BMS-488043, administered
      as monotherapy for 8 days, demonstrated significant viral load reductions. In
      order to examine the effects of AI monotherapy on HIV-1 sensitivity, phenotypic
      sensitivity assessment of baseline and postdosing (day 8) samples was performed.
      These analyses revealed that four subjects had emergent phenotypic resistance (a
      50% effective concentration [EC(50)] >10-fold greater than the baseline value)
      and four had high baseline EC(50)s (>200 nM). Population sequencing and sequence
      determination of cloned envelope genes uncovered five gp120 mutations at four
      loci (V68A, L116I, S375I/N, and M426L) associated with BMS-488043 resistance.
      Substitution at the 375 locus, located near the CD4 binding pocket, was the most
      common (maintained in 5/8 subjects at day 8). The five substitutions were
      evaluated for their effects on AI sensitivity through reverse genetics in
      functional envelopes, confirming their role in decreasing sensitivity to the
      drug. Additional analyses revealed that these substitutions did not alter
      sensitivity to other HIV-1 entry inhibitors. Thus, our studies demonstrate that
      although the majority of the subjects' viruses maintained sensitivity to BMS
      488043, substitutions can be selected that decrease HIV-1 susceptibility to the
      AI. Most importantly, the substitutions described here are not associated with
      resistance to other approved antiretrovirals, and therefore, attachment
      inhibitors could complement the current arsenal of anti-HIV agents.

PMID- 21078949
TI  - Roles of residues Cys69, Asn104, Phe160, Gly232, Ser237, and Asp240 in extended
      spectrum beta-lactamase Toho-1.
AB  - Toho-1, which is also designated CTX-M-44, is an extended-spectrum class A beta
      lactamase that has high activity toward cefotaxime. In this study, we
      investigated the roles of residues suggested to be critical for the substrate
      specificity expansion of Toho-1 in previous structural analyses. Six amino acid
      residues were replaced one by one with amino acids that are often observed in the
      corresponding position of non-extended-spectrum beta-lactamases. The mutants
      produced in Escherichia coli strains were analyzed both for their kinetic
      properties and their effect on drug susceptibilities. The results indicate that
      the substitutions of Asn104 and Ser237 have certain effects on expansion of
      substrate specificity, while those of Cys69 and Phe160 have less effect, and that
      of Asp240 has no effect on the hydrolysis of any substrates tested. Gly232, which
      had been assumed to increase the flexibility of the substrate binding site, was
      revealed not to be critical for the expansion of substrate specificity of this
      enzyme, although this substitution resulted in deleterious effects on expression
      and stability of the enzyme.

PMID- 21078950
TI  - Biomarker-assisted dose selection for safety and efficacy in early development of
      PNU-100480 for tuberculosis.
AB  - Tuberculosis is a serious global health threat for which new treatments are
      urgently needed. This study examined the safety, tolerability, pharmacokinetics,
      and pharmacodynamics of multiple ascending doses of the oxazolidinone PNU-100480
      in healthy volunteers, using biomarkers for safety and efficacy. Subjects were
      randomly assigned to PNU-100480 or placebo (4:1) at schedules of 100, 300, or 600
      mg twice daily or 1,200 mg daily for 14 days or a schedule of 600 mg twice daily
      for 28 days to which pyrazinamide was added on days 27 and 28. A sixth cohort was
      given linezolid at 300 mg daily for 4 days. Signs, symptoms, and routine safety
      tests were monitored. Bactericidal activity against Mycobacterium tuberculosis
      was measured in ex vivo whole-blood culture. Plasma drug and metabolite
      concentrations were compared to the levels required for inhibition of M.
      tuberculosis growth and 50% inhibition of mitochondrial protein synthesis. All
      doses were safe and well tolerated. There were no hematologic or other safety
      signals during 28 days of dosing at 600 mg twice daily. Plasma concentrations of
      PNU-100480 and metabolites at this dose remained below those required for 50%
      inhibition of mitochondrial protein synthesis. Cumulative whole-blood
      bactericidal activity of PNU-100480 at this dose (-0.316 +/- 0.04 log) was
      superior to the activities of all other doses tested (P < 0.001) and was
      significantly augmented by pyrazinamide (-0.420 +/- 0.06 log) (P = 0.002). In
      conclusion, PNU-100480 was safe and well tolerated at all tested doses. Further
      studies in patients with tuberculosis are warranted. Biomarkers can accelerate
      early development of new tuberculosis treatments.

PMID- 21078951
TI  - Antiviral activity, pharmacokinetics, and safety of BMS-488043, a novel oral
      small-molecule HIV-1 attachment inhibitor, in HIV-1-infected subjects.
AB  - BMS-488043 is a novel and unique oral small-molecule inhibitor of the attachment
      of human immunodeficiency virus type 1 (HIV-1) to CD4(+) lymphocytes. The
      antiviral activity, pharmacokinetics, viral susceptibility, and safety of BMS
      488043 were evaluated in an 8-day monotherapy trial. Thirty HIV-1-infected study
      subjects were randomly assigned to sequential, safety-guided dose panels of 800
      and 1,800 mg BMS-488043 or a matched placebo in a 4:1 ratio, and the drug was
      administered every 12 h with a high-fat meal for 7 days and on the morning of day
      8. Dose-related, albeit less-than-dose-proportional, increases in plasma BMS
      488043 concentrations were observed. Mean plasma HIV-1 RNA decreases from the
      baseline for the BMS-488043 800- and 1,800-mg dose groups on day 8 were 0.72 and
      0.96 log(10) copies/ml, respectively, compared with 0.02 log(10) copies/ml for
      the placebo group. A lower baseline BMS-488043 50% effective concentration
      (EC(50)) in the active-treatment groups was predictive of a greater antiviral
      response. Although absolute drug exposure was not associated with an antiviral
      response, the trough concentration (C(trough)), adjusted by the baseline EC(50)
      (C(trough)/EC(50)), was associated with antiviral activity. During dosing, four
      subjects experienced >10-fold reductions in viral susceptibility to BMS-488043,
      providing further support of the direct antiviral mechanism of BMS-488043. BMS
      488043 was generally safe and well tolerated. These results suggest that further
      development of this novel class of oral HIV-1 attachment inhibitors is warranted.

PMID- 21078952
TI  - Determinants of individual variation in intracellular accumulation of anti-HIV
      nucleoside analog metabolites.
AB  - Individual variation in response to antiretroviral therapy is well-known, but it
      is not clear if demographic characteristics such as gender, age, and ethnicity
      are responsible for the variation. To optimize anti-HIV therapy and guide
      antiretroviral drug discovery, determinants that cause variable responses to
      therapy need to be evaluated. We investigated the determinants of intracellular
      concentrations of nucleoside analogs using peripheral blood mononuclear cells
      from 40 healthy donors. We observed individual differences in the concentrations
      of the intracellular nucleoside analogs; the mean concentrations of the
      triphosphate metabolite of ethynylstavudine (4'-Ed4T), zidovudine (AZT), and
      lamivudine (3TC) were 0.71 pmol/10(6) cells (minimum and maximum, 0.10 and 3.00
      pmol/10(6) cells, respectively), 0.88 pmol/10(6) cells (minimum and maximum, 0.10
      and 15.18 pmol/10(6) cells, respectively), and 1.70 pmol/10(6) cells (minimum and
      maximum, 0.20 and 7.73 pmol/10(6) cells, respectively). Gender and ethnicity had
      no effect on the concentration of 4'-Ed4T and 3TC metabolites. There was a trend
      for moderation of the concentrations of AZT metabolites by gender (P = 0.17 for
      gender.metabolite concentration). We observed variability in the activity and
      expression of cellular kinases. There was no statistically significant
      correlation between thymidine kinase 1 (TK-1) activity or expression and
      thymidine analog metabolite concentrations. The correlation between the activity
      of deoxycytidine kinase (dCK) and the 3TC monophosphate metabolite concentration
      showed a trend toward significance (P = 0.1). We observed an inverse correlation
      between the multidrug-resistant protein 2 (MRP2) expression index and the
      concentrations of AZT monophosphate, AZT triphosphate, and total AZT metabolites.
      Our findings suggest that the observed variation in clinical response to
      nucleoside analogs may be due partly to the individual differences in the
      intracellular concentrations, which in turn may be affected by the cellular
      kinases involved in the phosphorylation pathway and ATP-binding cassette (ABC)
      transport proteins.

PMID- 21078953
TI  - Reconceptualizing the classification of PNAS articles.
AB  - PNAS article classification is rooted in long-standing disciplinary divisions
      that do not necessarily reflect the structure of modern scientific research. We
      reevaluate that structure using latent pattern models from statistical machine
      learning, also known as mixed-membership models, that identify semantic structure
      in co-occurrence of words in the abstracts and references. Our findings suggest
      that the latent dimensionality of patterns underlying PNAS research articles in
      the Biological Sciences is only slightly larger than the number of categories
      currently in use, but it differs substantially in the content of the categories.
      Further, the number of articles that are listed under multiple categories is only
      a small fraction of what it should be. These findings together with the
      sensitivity analyses suggest ways to reconceptualize the organization of papers
      published in PNAS.

PMID- 21078954
TI  - Multiple tail domain interactions stabilize nonmuscle myosin II bipolar
      filaments.
AB  - Contractile force transduction by myosin II derives from its assembly into
      bipolar filaments. The coiled-coil tail domain of the myosin II heavy chain
      mediates filament assembly, although the mechanism is poorly understood. Tail
      domains contain an alternating electrostatic repeat, yet only a small region of
      the tail (termed the "assembly domain") is typically required for assembly. Using
      computational analysis, mutagenesis, and electron microscopy we discovered that
      the assembly domain does not function through self-interaction as previously
      thought. Rather, the assembly domain acts as a unique, positively charged
      interaction surface that can stably contact multiple complementary, negatively
      charged surfaces in the upstream tail domain. The relative affinities of the
      assembly domain to each complementary interaction surface sets the characteristic
      molecular staggers observed in myosin II filaments. Together these results
      explain the relationship between the charge repeat and assembly domain in
      stabilizing myosin bipolar filaments.

PMID- 21078956
TI  - National housing and impervious surface scenarios for integrated climate impact
      assessments.
AB  - Understanding the impacts of climate change on people and the environment
      requires an understanding of the dynamics of both climate and land use/land cover
      changes. A range of future climate scenarios is available for the conterminous
      United States that have been developed based on widely used international
      greenhouse gas emissions storylines. Climate scenarios derived from these
      emissions storylines have not been matched with logically consistent land
      use/cover maps for the United States. This gap is a critical barrier to
      conducting effective integrated assessments. This study develops novel national
      scenarios of housing density and impervious surface cover that are logically
      consistent with emissions storylines. Analysis of these scenarios suggests that
      combinations of climate and land use/cover can be important in determining
      environmental conditions regulated under the Clean Air and Clean Water Acts. We
      found significant differences in patterns of habitat loss and the distribution of
      potentially impaired watersheds among scenarios, indicating that compact
      development patterns can reduce habitat loss and the number of impaired
      watersheds. These scenarios are also associated with lower global greenhouse gas
      emissions and, consequently, the potential to reduce both the drivers of
      anthropogenic climate change and the impacts of changing conditions. The
      residential housing and impervious surface datasets provide a substantial first
      step toward comprehensive national land use/land cover scenarios, which have
      broad applicability for integrated assessments as these data and tools are
      publicly available.

PMID- 21078955
TI  - Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated
      protein kinase kinase 6 by inhibiting ATP binding.
AB  - Mitogen-activated protein kinase kinase 6 (MKK6) is a member of the mitogen
      activated protein kinase (MAPK) kinase (MAP2K) subfamily that specifically
      phosphorylates and activates the p38 MAPKs. Based on both biochemical and
      cellular assays, we found that MKK6 was extremely sensitive to oxidation: It was
      inactivated by oxidation and its kinase activity was fully restored upon
      treatment with a reducing agent. Detailed mechanistic studies showed that
      cysteines 109 and 196, two of the six cysteines in MKK6, formed an intramolecular
      disulfide bond upon oxidation that inactivated MKK6 by inhibiting its ATP
      binding. This mechanism is distinct from that seen in other redox-sensitive
      kinases. The two cysteines involved in intramolecular disulfide formation are
      conserved in all seven members of the MAP2K family. Consistently, we confirmed
      that other MAP2Ks were also sensitive to oxidation. Our work reveals that MKK6
      and other MAP2Ks are a distinct class of cellular redox sensors.

PMID- 21078957
TI  - Silane plus molecular hydrogen as a possible pathway to metallic hydrogen.
AB  - The high-pressure behavior of silane, SiH(4), plus molecular hydrogen was
      investigated using a structural search method and ab initio molecular dynamics to
      predict the structures and examine the physical origin of the pressure-induced
      drop in hydrogen intramolecular vibrational (vibron) frequencies. A structural
      distortion is predicted at 15 GPa from a slightly strained fcc cell to a
      rhombohedral cell that involves a small volume change. The predicted equation of
      state and the pressure-induced drop in the hydrogen vibron frequencies reproduces
      well the experimental data (Strobel TA, Somayazulu M, Hemley RJ (2009) Phys Rev
      Lett 103:065701). The bond weakening in H(2) is induced by intermolecular
      interactions between the H(2) and SiH(4) molecules. A significant feature of the
      high-pressure structures of SiH(4)(H(2))(2) is the dynamical behavior of the H(2)
      molecules. It is found that H(2) molecules are rotating in this pressure range
      whereas the SiH(4) molecules remain rigid. The detailed nature of the
      interactions of molecular hydrogen with SiH(4) in SiH(4)(H(2))(2) is therefore
      strongly influenced by the dynamical behavior of the H(2) molecules in the high
      pressure structure. The phase with the calculated structure is predicted to
      become metallic near 120 GPa, which is significantly lower than the currently
      suggested pressure for metallization of bulk molecular hydrogen.

PMID- 21078958
TI  - Fluidization of tissues by cell division and apoptosis.
AB  - During the formation of tissues, cells organize collectively by cell division and
      apoptosis. The multicellular dynamics of such systems is influenced by mechanical
      conditions and can give rise to cell rearrangements and movements. We develop a
      continuum description of tissue dynamics, which describes the stress distribution
      and the cell flow field on large scales. In the absence of division and
      apoptosis, we consider the tissue to behave as an elastic solid. Cell division
      and apoptosis introduce stress sources that, in general, are anisotropic. By
      combining cell number balance with dynamic equations for the stress source, we
      show that the tissue effectively behaves as a viscoelastic fluid with a
      relaxation time set by the rates of division and apoptosis. If the system is
      confined in a fixed volume, it reaches a homeostatic state in which division and
      apoptosis balance. In this state, cells undergo a diffusive random motion driven
      by the stochasticity of division and apoptosis. We calculate the expression for
      the effective diffusion coefficient as a function of the tissue parameters and
      compare our results concerning both diffusion and viscosity to simulations of
      multicellular systems using dissipative particle dynamics.

PMID- 21078960
TI  - Apparent failure of the Born-Oppenheimer static surface model for vibrational
      excitation of molecular hydrogen on copper.
AB  - The accuracy of dynamical models for reactive scattering of molecular hydrogen,
      H(2), from metal surfaces is relevant to the validation of first principles
      electronic structure methods for molecules interacting with metal surfaces. The
      ability to validate such methods is important to progress in modeling
      heterogeneous catalysis. Here, we study vibrational excitation of H(2) on Cu(111)
      using the Born-Oppenheimer static surface model. The potential energy surface
      (PES) used was validated previously by calculations that reproduced experimental
      data on reaction and rotationally inelastic scattering in this system with
      chemical accuracy to within errors <= 1 kcal/mol ~ 4.2 kJ/mol [Diaz C, et al.
      (2009) Science 326:832-834]. Using the same PES and model, our dynamics
      calculations underestimate the contribution of vibrational excitation to
      previously measured time-of-flight spectra of H(2) scattered from Cu(111) by a
      factor 3. Given the accuracy of the PES for the experiments for which the Born
      Oppenheimer static surface model is expected to hold, we argue that modeling the
      effect of the surface degrees of freedom will be necessary to describe
      vibrational excitation with similar high accuracy.

PMID- 21078959
TI  - DNA search efficiency is modulated by charge composition and distribution in the
      intrinsically disordered tail.
AB  - Intrinsically disordered tails are common in DNA-binding proteins and can affect
      their search efficiency on nonspecific DNA by promoting the brachiation dynamics
      of intersegment transfer. During brachiation, the protein jumps between distant
      DNA regions via an intermediate state in which the tail and globular moieties are
      bound to different DNA segments. While the disordered tail must be long and
      positively charged to facilitate DNA search, the effect of its residue sequence
      on brachiation is unknown. We explored this issue using the NK-2 and Antp
      homeodomain transcription factors. We designed 566 NK-2 tail-variants and 55 Antp
      tail-variants having different net charges and positive charge distributions and
      studied their dynamics and DNA search efficiencies using coarse-grained molecular
      dynamics simulations. More intersegment transfers occur when the tail is
      moderately positively charged and the positive charges are clustered together in
      the middle of the tail or towards its N terminus. The presence of a negatively
      charged residue does not significantly affect protein brachiation, although it is
      likely that the presence of many negatively charged residues will complicate the
      DNA search mechanism. A bioinformatic analysis of 1,384 wild-type homeodomains
      illustrates that the charge composition and distribution in their N-tail
      sequences are consistent with an optimal charge pattern to promote intersegment
      transfer. Our study thus indicates that the residue sequence of the disordered
      tails of DNA-binding proteins has unique characteristics that were evolutionarily
      selected to achieve optimized function and suggests that the sequence-structure
      function paradigm known for structured proteins is valid for intrinsically
      disordered proteins as well.

PMID- 21078961
TI  - Modeling electrical activity of myocardial cells incorporating the effects of
      ephaptic coupling.
AB  - Existing models of electrical activity in myocardial tissue are unable to easily
      capture the effects of ephaptic coupling. Homogenized models do not account for
      cellular geometry, while detailed spatial models are too complicated to simulate
      in three dimensions. Here we propose a unique model that accurately captures the
      geometric effects while being computationally efficient. We use this model to
      provide an initial study of the effects of changes in extracellular geometry, gap
      junctional coupling, and sodium ion channel distribution on propagation velocity
      in a single 1D strand of cells. In agreement with previous studies, we find that
      ephaptic coupling increases propagation velocity at low gap junctional
      conductivity while it decreases propagation at higher conductivities. We also
      find that conduction velocity is relatively insensitive to gap junctional
      coupling when sodium ion channels are located entirely on the cell ends and cleft
      space is small. The numerical efficiency of this model, verified by comparison
      with more detailed simulations, allows a thorough study in parameter variation
      and shows that cellular structure and geometry has a nontrivial impact on
      propagation velocity. This model can be relatively easily extended to higher
      dimensions while maintaining numerical efficiency and incorporating ephaptic
      effects through modeling of complex, irregular cellular geometry.

PMID- 21078962
TI  - Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif.
AB  - The structure and integrity of DNA is of considerable biological and biomedical
      importance, and it is therefore critical to identify and to characterize enzymes
      that alter DNA structure. DNA helicases are ATP-driven motor proteins that unwind
      DNA. Conversely, HepA-related protein (HARP) protein (also known as SMARCAL1 and
      DNA-dependent ATPase A) is an annealing helicase that rewinds DNA in an ATP
      dependent manner. To date, HARP is the only known annealing helicase. Here we
      report the identification of a second annealing helicase, which we term AH2, for
      annealing helicase 2. Like HARP, AH2 catalyzes the ATP-dependent rewinding of
      replication protein A (RPA)-bound complementary single-stranded DNA, but does not
      exhibit any detectable helicase activity. Unlike HARP, however, AH2 lacks a
      conserved RPA-binding domain and does not interact with RPA. In addition, AH2
      contains an HNH motif, which is commonly found in bacteria and fungi and is often
      associated with nuclease activity. AH2 appears to be the only vertebrate protein
      with an HNH motif. Contrary to expectations, purified AH2 does not exhibit
      nuclease activity, but it remains possible that AH2 contains a latent nuclease
      that is activated under specific conditions. These structural and functional
      differences between AH2 and HARP suggest that different annealing helicases have
      distinct functions in the cell.

PMID- 21078963
TI  - Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated
      hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas.
AB  - EZH2, the catalytic subunit of the PRC2 complex, catalyzes the mono- through
      trimethylation of lysine 27 on histone H3 (H3K27). Histone H3K27 trimethylation
      is a mechanism for suppressing transcription of specific genes that are proximal
      to the site of histone modification. Point mutations of the EZH2 gene (Tyr641)
      have been reported to be linked to subsets of human B-cell lymphoma. The mutant
      allele is always found associated with a wild-type allele (heterozygous) in
      disease cells, and the mutations were reported to ablate the enzymatic activity
      of the PRC2 complex for methylating an unmodified peptide substrate. Here we
      demonstrate that the WT enzyme displays greatest catalytic efficiency (k(cat)/K)
      for the zero to monomethylation reaction of H3K27 and diminished efficiency for
      subsequent (mono- to di- and di- to trimethylation) reactions. In stark contrast,
      the disease-associated Y641 mutations display very limited ability to perform the
      first methylation reaction, but have enhanced catalytic efficiency for the
      subsequent reactions, relative to the WT enzyme. These results imply that the
      malignant phenotype of disease requires the combined activities of a H3K27
      monomethylating enzyme (PRC2 containing WT EZH2 or EZH1) together with the mutant
      PRC2s for augmented conversion of H3K27 to the trimethylated form. To our
      knowledge, this is the first example of a human disease that is dependent on the
      coordinated activities of normal and disease-associated mutant enzymatic
      function.

PMID- 21078964
TI  - p53-mediated apoptosis requires inositol hexakisphosphate kinase-2.
AB  - Inositol pyrophosphates have been implicated in numerous biological processes.
      Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol
      pyrophosphate, diphosphoinositol pentakisphosphate (IP7), influences apoptotic
      cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a
      transcriptional program leading to cell-cycle arrest or apoptosis. We demonstrate
      that IP6K2 is required for p53-mediated apoptosis and modulates the outcome of
      the p53 response. Gene disruption of IP6K2 in colorectal cancer cells selectively
      impairs p53-mediated apoptosis, instead favoring cell-cycle arrest. IP6K2 acts by
      binding directly to p53 and decreasing expression of proarrest gene targets such
      as the cyclin-dependent kinase inhibitor p21.

PMID- 21078966
TI  - Both catabolic and anabolic heterotrophic microbial activity proceed in frozen
      soils.
AB  - A large proportion of the global soil carbon pool is stored in soils of high
      latitude ecosystems in which microbial processes and production of greenhouse
      gases proceed during the winter months. It has been suggested that microorganisms
      have limited ability to sequester substrates at temperatures around and below 0 
      degrees C and that a metabolic shift to dominance of catabolic processes occurs
      around these temperatures. However, there are contrary indications that anabolic
      processes can proceed, because microbial growth has been observed at far lower
      temperatures. Therefore, we investigated the utilization of the microbial
      substrate under unfrozen and frozen conditions in a boreal forest soil across a
      temperature range from -9  degrees C to +9  degrees C, by using gas
      chromatography-isotopic ratio mass spectrometry and (13)C magic-angle spinning
      NMR spectroscopy to determine microbial turnover and incorporation of (13)C
      labeled glucose. Our results conclusively demonstrate that the soil
      microorganisms maintain both catabolic (CO(2) production) and anabolic (biomass
      synthesis) processes under frozen conditions and that no significant differences
      in carbon allocation from [(13)C]glucose into [(13)C]CO(2) and cell organic (13)C
      compounds occurred between +9  degrees C and -4  degrees C. The only significant
      metabolic changes detected were increased fluidity of the cell membranes
      synthesized at frozen conditions and increased production of glycerol in the
      frozen samples. The finding that the processes in frozen soil are similar to
      those in unfrozen soil has important implications for our general understanding
      and conceptualization of soil carbon dynamics in high-latitude ecosystems.

PMID- 21078965
TI  - Source identification in two criminal cases using phylogenetic analysis of HIV-1
      DNA sequences.
AB  - Phylogenetic analysis has been widely used to test the a priori hypothesis of
      epidemiological clustering in suspected transmission chains of HIV-1. Among
      studies showing strong support for relatedness between HIV samples obtained from
      infected individuals, evidence for the direction of transmission between
      epidemiologically related pairs has been lacking. During transmission of HIV, a
      genetic bottleneck occurs, resulting in the paraphyly of source viruses with
      respect to those of the recipient. This paraphyly establishes the direction of
      transmission, from which the source can then be inferred. Here, we present
      methods and results from two criminal cases, State of Washington v Anthony Eugene
      Whitfield, case number 04-1-0617-5 (Superior Court of the State of Washington,
      Thurston County, 2004) and State of Texas v Philippe Padieu, case numbers 219
      82276-07, 219-82277-07, 219-82278-07, 219-82279-07, 219-82280-07, and 219-82705
      07 (219th Judicial District Court, Collin County, TX, 2009), which provided
      evidence that direction can be established from blinded case samples. The
      observed paraphyly from each case study led to the identification of an inferred
      source (i.e., index case), whose identity was revealed at trial to be that of the
      defendant.

PMID- 21078967
TI  - Comparative genomics of clinical and environmental Vibrio mimicus.
AB  - Whether Vibrio mimicus is a variant of Vibrio cholerae or a separate species has
      been the subject of taxonomic controversy. A genomic analysis was undertaken to
      resolve the issue. The genomes of V. mimicus MB451, a clinical isolate, and
      VM223, an environmental isolate, comprise ca. 4,347,971 and 4,313,453 bp and
      encode 3,802 and 3,290 ORFs, respectively. As in other vibrios, chromosome I (C
      I) predominantly contains genes necessary for growth and viability, whereas
      chromosome II (C-II) bears genes for adaptation to environmental change. C-I
      harbors many virulence genes, including some not previously reported in V.
      mimicus, such as mannose-sensitive hemagglutinin (MSHA), and enterotoxigenic
      hemolysin (HlyA); C-II encodes a variant of Vibrio pathogenicity island 2 (VPI
      2), and Vibrio seventh pandemic island II (VSP-II) cluster of genes. Extensive
      genomic rearrangement in C-II indicates it is a hot spot for evolution and
      genesis of speciation for the genus Vibrio. The number of virulence regions
      discovered in this study (VSP-II, MSHA, HlyA, type IV pilin, PilE, and integron
      integrase, IntI4) with no notable difference in potential virulence genes between
      clinical and environmental strains suggests these genes also may play a role in
      the environment and that pathogenic strains may arise in the environment.
      Significant genome synteny with prototypic pre-seventh pandemic strains of V.
      cholerae was observed, and the results of phylogenetic analysis support the
      hypothesis that, in the course of evolution, V. mimicus and V. cholerae diverged
      from a common ancestor with a prototypic sixth pandemic genomic backbone.

PMID- 21078968
TI  - M3-muscarinic receptor promotes insulin release via receptor
      phosphorylation/arrestin-dependent activation of protein kinase D1.
AB  - The activity of G protein-coupled receptors is regulated via hyper
      phosphorylation following agonist stimulation. Despite the universal nature of
      this regulatory process, the physiological impact of receptor phosphorylation
      remains poorly studied. To address this question, we have generated a knock-in
      mouse strain that expresses a phosphorylation-deficient mutant of the M(3)
      muscarinic receptor, a prototypical G(q/11)-coupled receptor. This mutant mouse
      strain was used here to investigate the role of M(3)-muscarinic receptor
      phosphorylation in the regulation of insulin secretion from pancreatic islets.
      Importantly, the phosphorylation deficient receptor coupled to G(q/11)-signaling
      pathways but was uncoupled from phosphorylation-dependent processes, such as
      receptor internalization and beta-arrestin recruitment. The knock-in mice showed
      impaired glucose tolerance and insulin secretion, indicating that M(3)-muscarinic
      receptors expressed on pancreatic islets regulate glucose homeostasis via
      receptor phosphorylation-/arrestin-dependent signaling. The mechanism centers on
      the activation of protein kinase D1, which operates downstream of the recruitment
      of beta-arrestin to the phosphorylated M(3)-muscarinic receptor. In conclusion,
      our findings support the unique concept that M(3)-muscarinic receptor-mediated
      augmentation of sustained insulin release is largely independent of G protein
      coupling but involves phosphorylation-/arrestin-dependent coupling of the
      receptor to protein kinase D1.

PMID- 21078970
TI  - Association mapping of local climate-sensitive quantitative trait loci in
      Arabidopsis thaliana.
AB  - Flowering time (FT) is the developmental transition coupling an internal genetic
      program with external local and seasonal climate cues. The genetic loci sensitive
      to predictable environmental signals underlie local adaptation. We dissected
      natural variation in FT across a new global diversity set of 473 unique
      accessions, with >12,000 plants across two seasonal plantings in each of two
      simulated local climates, Spain and Sweden. Genome-wide association mapping was
      carried out with 213,497 SNPs. A total of 12 FT candidate quantitative trait loci
      (QTL) were fine-mapped in two independent studies, including 4 located within +/
      10 kb of previously cloned FT alleles and 8 novel loci. All QTL show sensitivity
      to planting season and/or simulated location in a multi-QTL mixed model. Alleles
      at four QTL were significantly correlated with latitude of origin, implying past
      selection for faster flowering in southern locations. Finally, maximum seed yield
      was observed at an optimal FT unique to each season and location, with four FT
      QTL directly controlling yield. Our results suggest that these major,
      environmentally sensitive FT QTL play an important role in spatial and temporal
      adaptation.

PMID- 21078971
TI  - Concomitant deletions of tumor suppressor genes MEN1 and AIP are essential for
      the pathogenesis of the brown fat tumor hibernoma.
AB  - Hibernomas are benign tumors with morphological features resembling brown fat.
      They consistently display cytogenetic rearrangements, typically translocations,
      involving chromosome band 11q13. Here we demonstrate that these aberrations are
      associated with concomitant deletions of AIP and MEN1, tumor suppressor genes
      that are located 3 Mb apart and that underlie the hereditary syndromes pituitary
      adenoma predisposition and multiple endocrine neoplasia type I. MEN1 and AIP
      displayed a low expression in hibernomas whereas the expression of genes up
      regulated in brown fat--PPARA, PPARG, PPARGC1A, and UCP1--was high. Thus, loss of
      MEN1 and AIP is likely to be pathogenetically essential for hibernoma
      development. Simultaneous loss of two tumor suppressor genes has not previously
      been shown to result from a neoplasia-associated translocation. Furthermore, in
      contrast to the prevailing assumption that benign tumors harbor relatively few
      genetic aberrations, the present analyses demonstrate that a considerable number
      of chromosome breaks are involved in the pathogenesis of hibernoma.

PMID- 21078972
TI  - Neanderthal symbolism and ornament manufacture: the bursting of a bubble?

PMID- 21078973
TI  - Neural signatures of autism.
AB  - Functional magnetic resonance imaging of brain responses to biological motion in
      children with autism spectrum disorder (ASD), unaffected siblings (US) of
      children with ASD, and typically developing (TD) children has revealed three
      types of neural signatures: (i) state activity, related to the state of having
      ASD that characterizes the nature of disruption in brain circuitry; (ii) trait
      activity, reflecting shared areas of dysfunction in US and children with ASD,
      thereby providing a promising neuroendophenotype to facilitate efforts to bridge
      genomic complexity and disorder heterogeneity; and (iii) compensatory activity,
      unique to US, suggesting a neural system-level mechanism by which US might
      compensate for an increased genetic risk for developing ASD. The distinct brain
      responses to biological motion exhibited by TD children and US are striking given
      the identical behavioral profile of these two groups. These findings offer far
      reaching implications for our understanding of the neural systems underlying
      autism.

PMID- 21078974
TI  - Neural basis of the undermining effect of monetary reward on intrinsic
      motivation.
AB  - Contrary to the widespread belief that people are positively motivated by reward
      incentives, some studies have shown that performance-based extrinsic reward can
      actually undermine a person's intrinsic motivation to engage in a task. This
      "undermining effect" has timely practical implications, given the burgeoning of
      performance-based incentive systems in contemporary society. It also presents a
      theoretical challenge for economic and reinforcement learning theories, which
      tend to assume that monetary incentives monotonically increase motivation.
      Despite the practical and theoretical importance of this provocative phenomenon,
      however, little is known about its neural basis. Herein we induced the behavioral
      undermining effect using a newly developed task, and we tracked its neural
      correlates using functional MRI. Our results show that performance-based monetary
      reward indeed undermines intrinsic motivation, as assessed by the number of
      voluntary engagements in the task. We found that activity in the anterior
      striatum and the prefrontal areas decreased along with this behavioral
      undermining effect. These findings suggest that the corticobasal ganglia
      valuation system underlies the undermining effect through the integration of
      extrinsic reward value and intrinsic task value.

PMID- 21078975
TI  - Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces
      fibrosis and improves cardiac function in a rat model of myocardial infarction.
AB  - Secreted frizzled related protein 2 (Sfrp2) is known as an inhibitor for the Wnt
      signaling. In recent studies, Sfrp2 has been reported to inhibit the activity of
      Xenopus homolog of mammalian Tolloid-like 1 metalloproteinase. Bone morphogenic
      protein 1 (Bmp1)/Tolloid-like metalloproteinase plays a key role in the
      regulation of collagen biosynthesis and maturation after tissue injury. Here, we
      showed both endogenous Sfrp2 and Bmp1 protein expressions were up-regulated in
      rat heart after myocardial infarction (MI). We hypothesize that Sfrp2 could
      inhibit mammalian Bmp1 activity and, hence, the exogenous administration of Sfrp2
      after MI would inhibit the deposition of mature collagen and improve heart
      function. Using recombinant proteins, we demonstrated that Sfrp2, but not Sfrp1
      or Sfrp3, inhibited Bmp1 activity in vitro as measured by a fluorogenic peptide
      based procollagen C-proteinase activity assay. We also demonstrated that Sfrp2 at
      high concentration inhibited human and rat type I procollagen processing by Bmp1
      in vitro. We further showed that exogenously added Sfrp2 inhibited type I
      procollagen maturation in primary cardiac fibroblasts. Two days after direct
      injection into the rat infarcted myocardium, Sfrp2 inhibited MI-induced type I
      collagen deposition. As early as 2 wk after injection, Sfrp2 significantly
      reduced left ventricular (LV) fibrosis as shown by trichrome staining. Four weeks
      after injection, Sfrp2 prevented the anterior wall thinning and significantly
      improved cardiac function as revealed by histological analysis and
      echocardiographic measurement. Our study demonstrates Sfrp2 at therapeutic doses
      can inhibit fibrosis and improve LV function at a later stage after MI.

PMID- 21078976
TI  - MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA
      MutS homolog 2 (hMSH2).
AB  - The overexpression of microRNA-21 (miR-21) is linked to a number of human tumors
      including colorectal cancer, where it appears to regulate the expression of tumor
      suppressor genes including p21, phosphatase and tensin homolog, TGFbeta receptor
      II, and B-cell leukemia/lymphoma 2 -associated X protein. Here we demonstrate
      that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition
      protein complex, human mutS homolog 2 (hMSH2) and 6 (hMSH6). Colorectal tumors
      that express a high level of miR-21 display reduced hMSH2 protein expression.
      Cells that overproduce miR-21 exhibit significantly reduced 5-fluorouracil (5-FU)
      induced G2/M damage arrest and apoptosis that is characteristic of defects in the
      core MMR component. Moreover, xenograft studies demonstrate that miR-21
      overexpression dramatically reduces the therapeutic efficacy of 5-FU. These
      studies suggest that the down-regulation of the MMR mutator gene associated with
      miR-21 overexpression may be an important clinical indicator of therapeutic
      efficacy in colorectal cancer.

PMID- 21078977
TI  - Forest transitions, trade, and the global displacement of land use.
AB  - Reducing tropical deforestation is an international priority, given its impacts
      on carbon emissions and biodiversity. We examined whether recent forest
      transitions--a shift from net deforestation to net reforestation--involved a
      geographic displacement of forest clearing across countries through trade in
      agricultural and forest products. In most of the seven developing countries that
      recently experienced a forest transition, displacement of land use abroad
      accompanied local reforestation. Additional global land-use change embodied in
      their net wood trade offset 74% of their total reforested area. Because the
      reforesting countries continued to export more agricultural goods than they
      imported, this net displacement offset 22% of their total reforested area when
      both agriculture and forestry sectors are included. However, this net
      displacement increased to 52% during the last 5 y. These countries thus have
      contributed to a net global reforestation and/or decrease in the pressure on
      forests, but this global environmental benefit has been shrinking during recent
      years. The net decrease in the pressure on forests does not account for
      differences in their ecological quality. Assessments of the impacts of
      international policies aimed at reducing global deforestation should integrate
      international trade in agricultural and forest commodities.

PMID- 21078978
TI  - {Beta}-blocker drugs mediate calcium signaling in native central nervous system
      neurons by {beta}-arrestin-biased agonism.
AB  - G protein-coupled receptors (GPCRs), the largest family of signaling receptors
      expressed in the CNS, mediate the neuropsychiatric effects of a diverse range of
      clinically relevant drugs. It is increasingly clear that GPCRs can activate
      distinct G protein-dependent and -independent transduction pathway(s), and that
      certain drugs differ in the ability to regulate distinct signaling mechanisms
      linked to the same receptors. A fundamental question in neuropharmacology is
      whether such "biased agonism" occurs in physiologically relevant neurons and with
      endogenous receptors. Here we show that propranolol and carvedilol, two beta
      blocker drugs that inhibit beta-adrenergic signaling via heterotrimeric G
      proteins, function in hippocampal pyramidal neurons as potent and selective
      activators of an alternate receptor-linked calcium signaling pathway mediated by
      beta-arrestin-2 and ERK1/2. Our results support the emerging view of beta
      arrestin-biased agonism as a significant mechanism of drug action and do so in
      CNS-derived neurons expressing only native receptors.

PMID- 21078979
TI  - Consciousness of the first order in blindsight.
AB  - At suprathreshold levels, detection and awareness of visual stimuli are typically
      synonymous in nonclinical populations. But following postgeniculate lesions, some
      patients may perform above chance in forced-choice detection paradigms, while
      reporting not to see the visual events presented within their blind field. This
      phenomenon, termed "blindsight," is intriguing because it demonstrates a
      dissociation between detection and perception. It is possible, however, for a
      blindsight patient to have some "feeling" of the occurrence of an event without
      seeing per se. This is termed blindsight type II to distinguish it from the type
      I, defined as discrimination capability in the total absence of any acknowledged
      awareness. Here we report on a well-studied patient, D.B., whose blindsight
      capabilities have been previously documented. We have found that D.B. is capable
      of detecting visual patterns defined by changes in luminance (first-order
      gratings) and those defined by contrast modulation of textured patterns (textured
      gratings; second-order stimuli) while being aware of the former but reporting no
      awareness of the latter. We have systematically investigated the parameters that
      could lead to visual awareness of the patterns and show that mechanisms
      underlying the subjective reports of visual awareness rely primarily on low
      spatial frequency, first-order spatial components of the image.

PMID- 21078980
TI  - Foundational model of structural connectivity in the nervous system with a schema
      for wiring diagrams, connectome, and basic plan architecture.
AB  - The nervous system is a biological computer integrating the body's reflex and
      voluntary environmental interactions (behavior) with a relatively constant
      internal state (homeostasis)-- promoting survival of the individual and species.
      The wiring diagram of the nervous system's structural connectivity provides an
      obligatory foundational model for understanding functional localization at
      molecular, cellular, systems, and behavioral organization levels. This paper
      provides a high-level, downwardly extendible, conceptual framework--like a
      compass and map--for describing and exploring in neuroinformatics systems (such
      as our Brain Architecture Knowledge Management System) the structural
      architecture of the nervous system's basic wiring diagram. For this, the
      Foundational Model of Connectivity's universe of discourse is the structural
      architecture of nervous system connectivity in all animals at all resolutions,
      and the model includes two key elements--a set of basic principles and an
      internally consistent set of concepts (defined vocabulary of standard terms)-
      arranged in an explicitly defined schema (set of relationships between concepts)
      allowing automatic inferences. In addition, rules and procedures for creating and
      modifying the foundational model are considered. Controlled vocabularies with
      broad community support typically are managed by standing committees of experts
      that create and refine boundary conditions, and a set of rules that are available
      on the Web.

PMID- 21078981
TI  - Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin
      transporters.
AB  - Arsenic is an extremely toxic metalloid causing serious health problems. In
      Southeast Asia, aquifers providing drinking and agricultural water for tens of
      millions of people are contaminated with arsenic. To reduce nutritional arsenic
      intake through the consumption of contaminated plants, identification of the
      mechanisms for arsenic accumulation and detoxification in plants is a
      prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate
      heavy metals and metalloids such as arsenic, thereby functioning as the first
      step in their detoxification. Plant vacuoles act as final detoxification stores
      for heavy metals and arsenic. The essential PC-metal(loid) transporters that
      sequester toxic metal(loid)s in plant vacuoles have long been sought but remain
      unidentified in plants. Here we show that in the absence of two ABCC-type
      transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to
      arsenic and arsenic-based herbicides. Heterologous expression of these ABCC
      transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic
      tolerance and accumulation. Furthermore, membrane vesicles isolated from these
      yeasts exhibited a pronounced arsenite [As(III)]-PC(2) transport activity.
      Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very
      low residual As(III)-PC(2) transport activity, and interestingly, less PC was
      produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and
      AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings
      demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC
      transporters. Modulation of vacuolar PC transporters in other plants may allow
      engineering of plants suited either for phytoremediation or reduced accumulation
      of arsenic in edible organs.

PMID- 21078982
TI  - Specific posttranslational modification regulates early events in mammary
      carcinoma formation.
AB  - The expression of an enzyme, GnT-V, that catalyzes a specific posttranslational
      modification of a family of glycoproteins, namely a branched N-glycan, is
      transcriptionally up-regulated during breast carcinoma oncogenesis. To determine
      the molecular basis of how early events in breast carcinoma formation are
      regulated by GnT-V, we studied both the early stages of mammary tumor formation
      by using 3D cell culture and a her-2 transgenic mouse mammary tumor model.
      Overexpression of GnT-V in MCF-10A mammary epithelial cells in 3D culture
      disrupted acinar morphogenesis with impaired hollow lumen formation, an early
      characteristic of mammary neoplastic transformation. The disrupted acinar
      morphogenesis of mammary tumor cells in 3D culture caused by her-2 expression was
      reversed in tumors that lacked GnT-V expression. Moreover, her-2-induced mammary
      tumor onset was significantly delayed in the GnT-V null tumors, evidence that the
      lack of the posttranslational modification catalyzed by GnT-V attenuated tumor
      formation. Inhibited activation of both PKB and ERK signaling pathways was
      observed in GnT-V null tumor cells. The proportion of tumor-initiating cells
      (TICs) in the mammary tumors from GnT-V null mice was significantly reduced
      compared with controls, and GnT-V null TICs displayed a reduced ability to form
      secondary tumors in NOD/SCID mice. These results demonstrate that GnT-V
      expression and its branched glycan products effectively modulate her-2-mediated
      signaling pathways that, in turn, regulate the relative proportion of tumor
      initiating cells and the latency of her-2-driven tumor onset.

PMID- 21078983
TI  - RD3, the protein associated with Leber congenital amaurosis type 12, is required
      for guanylate cyclase trafficking in photoreceptor cells.
AB  - Guanylate cyclases, GC1 and GC2, are localized in the light-sensitive outer
      segment compartment of photoreceptor cells, where they play a crucial role in
      phototransduction by catalyzing the synthesis of cGMP, the second messenger of
      phototransduction, and regulating intracellular Ca(2+) levels in combination with
      the cGMP-gated channel. Mutations in GC1 are known to cause Leber congenital
      amaurosis type 1 (LCA1), a childhood disease associated with severe vision loss.
      Although the enzymatic and regulatory properties of guanylate cyclases have been
      studied extensively, the molecular determinants responsible for their trafficking
      in photoreceptors remain unknown. Here we show that RD3, a protein of unknown
      function encoded by a gene associated with photoreceptor degeneration in humans
      with Leber congenital amaurosis type 12 (LCA12), the rd3 mouse, and rcd2 collie,
      colocalizes and interacts with GC1 and GC2 in rod and cone photoreceptor cells of
      normal mice. GC1 and GC2 are undetectable in photoreceptors of the rd3 mouse
      deficient in RD3 by immunofluorescence microscopy. Cell expression studies show
      that RD3 mediates the export of GC1 from the endoplasmic reticulum to endosomal
      vesicles, and that the C terminus of GC1 is required for RD3 binding. Our results
      indicate that photoreceptor degeneration in the rd3 mouse, rcd2 dog, and LCA12
      patients is caused by impaired RD3-mediated guanylate cyclase expression and
      trafficking. The resulting deficiency in cGMP synthesis and the constitutive
      closure of cGMP-gated channels might cause a reduction in intracellular Ca(2+) to
      a level below that required for long-term photoreceptor cell survival.

PMID- 21078984
TI  - RNA-mediated epigenetic regulation of DNA copy number.
AB  - Increasing evidence suggests that parentally supplied RNA plays crucial roles
      during eukaryotic development. This epigenetic contribution may regulate gene
      expression from the earliest stages. Although present in a variety of eukaryotes,
      maternally inherited characters are especially prominent in ciliated protozoa, in
      which parental noncoding RNA molecules instruct whole-genome reorganization. This
      includes removal of nearly all noncoding DNA and sorting the remaining fragments,
      producing extremely gene-rich somatic genomes. Chromosome fragmentation and
      extensive replication produce variable DNA copy numbers in the somatic genome.
      Understanding the forces that drive and regulate copy number change is
      fundamental. We show that RNA molecules present in parental cells during sexual
      reproduction can regulate chromosome copy number in the developing nucleus of the
      ciliate Oxytricha. Experimentally induced changes in RNA abundance can both
      increase and decrease the levels of corresponding DNA molecules in progeny,
      demonstrating epigenetic inheritance of chromosome copy number. These results
      suggest that maternal RNA, in addition to controlling gene expression or DNA
      processing, can also program DNA amplification levels.

PMID- 21078985
TI  - Configurational approach to identifying the earliest hominin butchers.
AB  - The announcement of two approximately 3.4-million-y-old purportedly butchered
      fossil bones from the Dikika paleoanthropological research area (Lower Awash
      Valley, Ethiopia) could profoundly alter our understanding of human evolution.
      Butchering damage on the Dikika bones would imply that tool-assisted meat-eating
      began approximately 800,000 y before previously thought, based on butchered bones
      from 2.6- to 2.5-million-y-old sites at the Ethiopian Gona and Bouri localities.
      Further, the only hominin currently known from Dikika at approximately 3.4 Ma is
      Australopithecus afarensis, a temporally and geographically widespread species
      unassociated previously with any archaeological evidence of butchering. Our
      taphonomic configurational approach to assess the claims of A. afarensis butchery
      at Dikika suggests the claims of unexpectedly early butchering at the site are
      not warranted. The Dikika research group focused its analysis on the morphology
      of the marks in question but failed to demonstrate, through recovery of similarly
      marked in situ fossils, the exact provenience of the published fossils, and
      failed to note occurrences of random striae on the cortices of the published
      fossils (incurred through incidental movement of the defleshed specimens across
      and/or within their abrasive encasing sediments). The occurrence of such random
      striae (sometimes called collectively "trampling" damage) on the two fossils
      provide the configurational context for rejection of the claimed butchery marks.
      The earliest best evidence for hominin butchery thus remains at 2.6 to 2.5 Ma,
      presumably associated with more derived species than A. afarensis.

PMID- 21078986
TI  - Comprehensive genetic testing for hereditary hearing loss using massively
      parallel sequencing.
AB  - The extreme genetic heterogeneity of nonsyndromic hearing loss (NSHL) makes
      genetic diagnosis expensive and time consuming using available methods. To assess
      the feasibility of target-enrichment and massively parallel sequencing
      technologies to interrogate all exons of all genes implicated in NSHL, we tested
      nine patients diagnosed with hearing loss. Solid-phase (NimbleGen) or solution
      based (SureSelect) sequence capture, followed by 454 or Illumina sequencing,
      respectively, were compared. Sequencing reads were mapped using GSMAPPER, BFAST,
      and BOWTIE, and pathogenic variants were identified using a custom-variant
      calling and annotation pipeline (ASAP) that incorporates publicly available in
      silico pathogenicity prediction tools (SIFT, BLOSUM, Polyphen2, and Align-GVGD).
      Samples included one negative control, three positive controls (one biological
      replicate), and six unknowns (10 samples total), in which we genotyped 605 single
      nucleotide polymorphisms (SNPs) by Sanger sequencing to measure sensitivity and
      specificity for SureSelect-Illumina and NimbleGen-454 methods at saturating
      sequence coverage. Causative mutations were identified in the positive controls
      but not in the negative control. In five of six idiopathic hearing loss patients
      we identified the pathogenic mutation. Massively parallel sequencing technologies
      provide sensitivity, specificity, and reproducibility at levels sufficient to
      perform genetic diagnosis of hearing loss.

PMID- 21078987
TI  - Stable and dynamic cortical electrophysiology of induction and emergence with
      propofol anesthesia.
AB  - The mechanism(s) by which anesthetics reversibly suppress consciousness are
      incompletely understood. Previous functional imaging studies demonstrated dynamic
      changes in thalamic and cortical metabolic activity, as well as the maintained
      presence of metabolically defined functional networks despite the loss of
      consciousness. However, the invasive electrophysiology associated with these
      observations has yet to be studied. By recording electrical activity directly
      from the cortical surface, electrocorticography (ECoG) provides a powerful method
      to integrate spatial, temporal, and spectral features of cortical
      electrophysiology not possible with noninvasive approaches. In this study, we
      report a unique comprehensive recording of invasive human cortical physiology
      during both induction and emergence from propofol anesthesia. Propofol-induced
      transitions in and out of consciousness (defined here as responsiveness) were
      characterized by maintained large-scale functional networks defined by correlated
      fluctuations of the slow cortical potential (<0.5 Hz) over the somatomotor
      cortex, present even in the deeply anesthetized state of burst suppression.
      Similarly, phase-power coupling between theta- and gamma-range frequencies
      persisted throughout the induction and emergence from anesthesia. Superimposed on
      this preserved functional architecture were alterations in frequency band power,
      variance, covariance, and phase-power interactions that were distinct to
      different frequency ranges and occurred in separable phases. These data support
      that dynamic alterations in cortical and thalamocortical circuit activity occur
      in the context of a larger stable architecture that is maintained despite
      anesthetic-induced alterations in consciousness.

PMID- 21078988
TI  - Dental evidence for ontogenetic differences between modern humans and
      Neanderthals.
AB  - Humans have an unusual life history, with an early weaning age, long childhood,
      late first reproduction, short interbirth intervals, and long lifespan. In
      contrast, great apes wean later, reproduce earlier, and have longer intervals
      between births. Despite 80 y of speculation, the origins of these developmental
      patterns in Homo sapiens remain unknown. Because they record daily growth during
      formation, teeth provide important insights, revealing that australopithecines
      and early Homo had more rapid ontogenies than recent humans. Dental development
      in later Homo species has been intensely debated, most notably the issue of
      whether Neanderthals and H. sapiens differ. Here we apply synchrotron virtual
      histology to a geographically and temporally diverse sample of Middle Paleolithic
      juveniles, including Neanderthals, to assess tooth formation and calculate age at
      death from dental microstructure. We find that most Neanderthal tooth crowns grew
      more rapidly than modern human teeth, resulting in significantly faster dental
      maturation. In contrast, Middle Paleolithic H. sapiens juveniles show greater
      similarity to recent humans. These findings are consistent with recent cranial
      and molecular evidence for subtle developmental differences between Neanderthals
      and H. sapiens. When compared with earlier hominin taxa, both Neanderthals and H.
      sapiens have extended the duration of dental development. This period of dental
      immaturity is particularly prolonged in modern humans.

PMID- 21078989
TI  - Increased expression of leukotriene C4 synthase and predominant formation of
      cysteinyl-leukotrienes in human abdominal aortic aneurysm.
AB  - Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the
      pathogenesis and progression of diverse inflammatory disorders. The cysteinyl
      leukotrienes LTC(4), LTD(4), and LTE(4) are important mediators of asthma, and
      LTB(4) has recently been implicated in atherosclerosis. Here we report that mRNA
      levels for the three key enzymes/proteins in the biosynthesis of cysteinyl
      leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC(4)
      synthase (LTC(4)S), are significantly increased in the wall of human abdominal
      aortic aneurysms (AAAs). In contrast, mRNA levels of LTA(4) hydrolase, the enzyme
      responsible for the biosynthesis of LTB(4), are not increased.
      Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP,
      and LTC(4)S proteins in the media and adventitia, localized in areas rich in
      inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA
      wall tissue converts arachidonic acid and the unstable epoxide LTA(4) into
      significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB(4).
      Furthermore, challenge of AAA wall tissue with exogenous LTD(4) increases the
      release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of
      the CysLT1 receptor by montelukast blocks this effect. The increased expression
      of LTC(4)S, together with the predominant formation of cysteinyl-leukotrienes and
      effects on MMPs production, suggests a mechanism by which LTs may promote matrix
      degradation in the AAA wall and identify the components of the cysteinyl
      leukotriene pathway as potential targets for prevention and treatment of AAA.

PMID- 21078990
TI  - ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein
      composition and decreases protein import.
AB  - Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1
      preferentially associates with the cytoplasmic face of mitochondria from spinal
      cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and
      multidimensional liquid chromatography, in combination with tandem mass
      spectrometry, revealed 33 proteins that were increased and 21 proteins that were
      decreased in SOD1(G93A) rat spinal cord mitochondria compared with SOD1(WT)
      spinal cord mitochondria. Analysis of this group of proteins revealed a higher
      than-expected proportion involved in complex I and protein import pathways.
      Direct import assays revealed a 30% decrease in protein import only in spinal
      cord mitochondria, despite an increase in the mitochondrial import components
      TOM20, TOM22, and TOM40. Recombinant SOD1(G93A) or SOD1(G85R), but not SOD1(WT)
      or a Parkinson's disease-causing, misfolded alpha-synuclein(E46K) mutant,
      decreased protein import by >50% in nontransgenic mitochondria from spinal cord,
      but not from liver. Thus, altered mitochondrial protein content accompanied by
      selective decreases in protein import into spinal cord mitochondria comprises
      part of the mitochondrial damage arising from mutant SOD1.

PMID- 21078991
TI  - Profile of Shelley E. Taylor. Interview by Beth Azar.

PMID- 21078992
TI  - Neural crest origin of olfactory ensheathing glia.
AB  - Olfactory ensheathing cells (OECs) are a unique class of glial cells with
      exceptional translational potential because of their ability to support axon
      regeneration in the central nervous system. Although OECs are similar in many
      ways to immature and nonmyelinating Schwann cells, and can myelinate large
      diameter axons indistinguishably from myelination by Schwann cells, current dogma
      holds that OECs arise from the olfactory epithelium. Here, using fate-mapping
      techniques in chicken embryos and genetic lineage tracing in mice, we show that
      OECs in fact originate from the neural crest and hence share a common
      developmental heritage with Schwann cells. This explains the similarities between
      OECs and Schwann cells and overturns the existing dogma on the developmental
      origin of OECs. Because neural crest stem cells persist in adult tissue,
      including skin and hair follicles, our results also raise the possibility that
      patient-derived neural crest stem cells could in the future provide an abundant
      and accessible source of autologous OECs for cell transplantation therapy for the
      injured central nervous system.

PMID- 21078993
TI  - Hippo signaling regulates Drosophila intestine stem cell proliferation through
      multiple pathways.
AB  - Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for
      maintaining tissue homeostasis and replenishing lost cells in response to tissue
      damage. Here we demonstrate that the Hippo (Hpo) signaling pathway, an
      evolutionarily conserved pathway implicated in organ size control and
      tumorigenesis, plays an essential role in regulating ISC proliferation. Loss of
      Hpo signaling in either midgut precursor cells or epithelial cells stimulates ISC
      proliferation. We provide evidence that loss of Hpo signaling in epithelial cells
      increases the production of cytokines of the Upd family and multiple EGFR ligands
      that activate JAK-STAT and EGFR signaling pathways in ISCs to stimulate their
      proliferation, thus revealing a unique non-cell-autonomous role of Hpo signaling
      in blocking ISC proliferation. Finally, we show that the Hpo pathway mediator
      Yorkie (Yki) is also required in precursor cells for injury-induced ISC
      proliferation in response to tissue-damaging reagent DSS.

PMID- 21078994
TI  - Paradoxical effects of constitutive human IL-32{gamma} in transgenic mice during
      experimental colitis.
AB  - Inflammatory cytokines mediate inflammatory bowel diseases (IBDs) and cytokine
      blocking therapies often ameliorate the disease severity. IL-32 affects
      inflammation by increasing the production of IL-1, TNFalpha, and several
      chemokines. Here, we investigated the role of IL-32 in intestinal inflammation by
      generating a transgenic (TG) mouse expressing human IL-32gamma (IL-32gamma TG).
      Although IL-32gamma TG mice are healthy, constitutive serum and colonic tissue
      levels of TNFalpha are elevated. Compared with wild-type (WT) mice, IL-32gamma TG
      mice exhibited a modestly exacerbated acute inflammation early following the
      initiation of dextran sodium sulfate (DSS)-induced colitis. However, after 6 d,
      there was less colonic inflammation, reduced tissue loss, and improved survival
      rate compared with WT mice. Associated with attenuated tissue damage, colonic
      levels of TNFalpha and IL-6 were significantly reduced in the IL-32gamma TG mice
      whereas IL-10 was elevated. Cultured colon explants from IL-32gamma TG mice
      secreted higher levels of IL-10 compared with WT mice and lower levels of
      TNFalpha and IL-6. Constitutive levels of IL-32gamma itself in colonic tissues
      were significantly lower following DSS colitis. Although the highest level of
      serum IL-32gamma occurred on day 3 of colitis, IL-32 was below constitutive
      levels on day 9. The ability of IL-32gamma to increase constitutive IL-10 likely
      reduces TNFalpha, IL-6, and IL-32 itself accounting for less inflammation. In
      humans with ulcerative colitis (UC), serum IL-32 is elevated and colonic biopsies
      contain IL-32 in inflamed tissues but not in uninvolved tissues. Thus IL-32gamma
      emerges as an example of how innate inflammation worsens as well as protects
      intestinal integrity.

PMID- 21078996
TI  - Learning optimal strategies in complex environments.

PMID- 21078995
TI  - Conserved mechanism for sensor phosphatase control of two-component signaling
      revealed in the nitrate sensor NarX.
AB  - Two-component signal transduction mediates a wide range of phenotypes in microbes
      and plants. The sensor transmitter module controls the phosphorylation state of
      the cognate-response-regulator receiver domain. Whereas the two-component
      autokinase and phosphotransfer reactions are well-understood, the mechanism by
      which sensors accelerate the rate of phospho-response regulator
      dephosphorylation, termed "transmitter phosphatase activity," is unknown. We
      identified a conserved DxxxQ motif adjacent to the phospho-accepting His residue
      in the HisKA_3 subfamily of two-component sensors. We used site-specific
      mutagenesis to make substitutions for these conserved Gln and Asp residues in the
      nitrate-responsive NarX sensor and analyzed function both in vivo and in vitro.
      Results show that the Gln residue is critical for transmitter phosphatase
      activity, but is not essential for autokinase or phosphotransfer activities. The
      documented role of an amide moiety in phosphoryl group hydrolysis suggests an
      analogous catalytic function for this Gln residue in HisKA_3 members. Results
      also indicate that the Asp residue is important for both autokinase and
      transmitter phosphatase activities. Furthermore, we noted that sensors of the
      HisKA subfamily exhibit an analogous E/DxxT/N motif, the conserved Thr residue of
      which is critical for transmitter phosphatase activity of the EnvZ sensor. Thus,
      two-component sensors likely use similar mechanisms for receiver domain
      dephosphorylation.

PMID- 21078997
TI  - Crystal structure of a reverse polymerase.

PMID- 21078998
TI  - Intron retention facilitates splice variant diversity in calcium-activated big
      potassium channel populations.
AB  - We report that the stress axis-regulated exon (STREX)-containing calcium
      activated big potassium (BKCa) channel splice variant expression and physiology
      are regulated in part by cytoplasmic splicing and intron retention. NextGen
      sequencing of the mRNA complement of pooled hippocampal dendrite samples found
      intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA.
      Further molecular analyses of i17a revealed that the majority of i17a-containing
      BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX
      protein immunocytochemistry demonstrated both reduced levels and altered
      subcellular distribution of STREX-containing BKCa channel protein. Selective
      reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst
      firing properties of hippocampal neurons. Collectively, these data show that
      STREX splice variant regulation via cytoplasmic splicing and intron retention
      helps generate STREX-dependent BKCa current diversity in hippocampal neurons.

PMID- 21078999
TI  - Multiple oncogenic mutations and clonal relationship in spatially distinct benign
      human epidermal tumors.
AB  - Malignant tumors result from the accumulation of genetic alterations in oncogenes
      and tumor suppressor genes. Much less is known about the genetic changes in
      benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal
      tumors without malignant potential. We performed a comprehensive mutational
      screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT
      pathways from 175 SK, including multiple lesions from each patient. SK commonly
      harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS,
      EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite
      the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK
      and PI3K pathway signaling, we did not find induction of senescence or a DNA
      damage response. Array comparative genomic hybridization (aCGH) analysis revealed
      that SK are genetically stable. The pattern of oncogenic mutations and X
      chromosome inactivation departs significantly from randomness and indicates that
      spatially independent lesions from a given patient share a clonal relationship.
      Our findings show that multiple oncogenic mutations in the major signaling
      pathways involved in cancer are not sufficient to drive malignant tumor
      progression. Furthermore, our data provide clues on the origin and spread of
      oncogenic mutations in tissues, suggesting that apparently independent
      (multicentric) adult benign tumors may have a clonal origin.

PMID- 21079001
TI  - The 50th anniversary of the ASCB: celebrating by looking forward.

PMID- 21079000
TI  - miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and
      contractility during pregnancy and labor.
AB  - Throughout most of pregnancy, uterine quiescence is maintained by increased
      progesterone receptor (PR) transcriptional activity, whereas spontaneous labor is
      initiated/facilitated by a concerted series of biochemical events that activate
      inflammatory pathways and have a negative impact on PR function. In this study,
      we uncovered a previously undescribed regulatory pathway whereby micro-RNAs
      (miRNAs) serve as hormonally modulated and conserved mediators of contraction
      associated genes in the pregnant uterus in the mouse and human. Using miRNA and
      gene expression microarray analyses of uterine tissues, we identified a conserved
      family of miRNAs, the miR-200 family, that is highly induced at term in both mice
      and humans as well as two coordinately down-regulated targets, zinc finger E-box
      binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors.
      We also observed up-regulation of the miR-200 family and down-regulation of ZEB1
      and ZEB2 in two different mouse models of preterm labor. We further demonstrated
      that ZEB1 is directly up-regulated by the action of progesterone (P(4))/PR at the
      ZEB1 promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of
      the contraction-associated genes, oxytocin receptor and connexin-43, and block
      oxytocin-induced contractility in human myometrial cells. Together, these
      findings implicate the miR-200 family and their targets, ZEB1 and ZEB2, as unique
      P(4)/PR-mediated regulators of uterine quiescence and contractility during
      pregnancy and labor and shed light on the molecular mechanisms involved in
      preterm birth.

PMID- 21079002
TI  - Finding a niche.
AB  - Although I always knew I wanted to be a scientist, I didn't know I would become a
      cell biologist. Events in life that you would never have predicted can greatly
      impact your career trajectory. I have learned to let those events take me in new
      directions. Following a desire to investigate an understudied area of cell
      biology, I have found a niche. In this area, my lab is poised to contribute
      significantly toward understanding the fundamental molecular mechanisms
      underlying polarized plant cell growth.

PMID- 21079003
TI  - The joy of a career in cell biology.
AB  - Science is a career where you do what you love everyday. Our science is built on
      the shoulders of those who came before us, and in turn we provide shoulders for
      our students and colleagues to build upon. Of course, seeing the seeds of ideas
      that we plant bear fruit as interesting science is why I love being a scientist.
      Looking back it also has been a particularly gratifying challenge to mentor
      members of the younger generation in building their careers.

PMID- 21079004
TI  - Diversifying the biological sciences: past efforts and future challenges.
AB  - I am honored to receive the E. E. Just Award for 2010. In my invited essay, I
      have opted to discuss the state of diversity in the biological sciences with some
      recommendations for moving forward toward a more positive and inclusive academy.
      The need to develop cohorts of minority scientists as support groups and to serve
      as role models within our institutions is stressed, along with the need to ensure
      that minority scientists are truly included in all aspects of the academy. It is
      imperative that we increase our efforts to prepare for the unique challenges that
      we will face as the United States approaches a "majority minority" population in
      the next 50 years.

PMID- 21079005
TI  - A preliminary report on my life in science.
AB  - I describe my wanderings from the United States to East Germany and back. I hope
      this gives a glimpse of science in East Germany and encourages people who do
      science under less than favorable conditions. Although elements of my story are
      unique, the main points are general: don't be afraid to start something new; it
      pays to be persistent; and science is a passion--if it feels like fun, you've
      probably got it right.

PMID- 21079006
TI  - A fascination with sugars.
AB  - We now recognize that a large number of membrane and soluble proteins contain
      covalently linked oligosaccharides that exhibit a vast array of structures and
      participate in a wide variety of biological processes. Nowhere is this better
      illustrated than the mannose 6-phosphate (Man-6-P) recognition system that
      mediates the trafficking of newly synthesized acid hydrolases to lysosomes in
      higher eukaryotes. The Asn-linked high-mannose oligosaccharides of these
      hydrolases facilitate folding of the nascent proteins in the endoplasmic
      reticulum via interaction with lectin-type chaperones and after phosphorylation
      in the Golgi, function as ligands for binding to Man-6-P receptors, a critical
      step in their transport to lysosomes. Failure to synthesize the Man-6-P
      recognition marker results in a serious lysosomal storage disease, one of a
      growing number of genetic conditions, termed congenital disorders of
      glycosylation, that result from faulty glycan biosynthesis.

PMID- 21079007
TI  - The future of Golgi research.
AB  - This essay looks backward on the past three decades of research toward
      understanding the mechanism of macromolecular traffic through and within the
      Golgi apparatus with an eye to the future. I also explain why I feel the Golgi
      should continue to hold the attention of molecular cell biologists.

PMID- 21079009
TI  - Cell biology: the endless frontier.

PMID- 21079008
TI  - Charting the secretory pathway in a simple eukaryote.
AB  - George Palade, a founding father of cell biology and of the American Society for
      Cell Biology (ASCB), established the ultrastructural framework for an analysis of
      how proteins are secreted and membranes are assembled in eukaryotic cells. His
      vision inspired a generation of investigators to probe the molecular mechanisms
      of protein transport. My laboratory has dissected these pathways with
      complementary genetic and biochemical approaches. Peter Novick, one of my first
      graduate students, isolated secretion mutants of Saccharomyces cerevisiae, and
      through cytological analysis of single and double mutants and molecular cloning
      of the corresponding SEC genes, we established that yeast cells use a secretory
      pathway fundamentally conserved in all eukaryotes. A biochemical reaction that
      recapitulates the first half of the secretory pathway was used to characterize
      Sec proteins that comprise the polypeptide translocation channel in the
      endoplasmic reticulum (ER) membrane (Sec61) and the cytoplasmic coat protein
      complex (COPII) that captures cargo proteins into transport vesicles that bud
      from the ER.

PMID- 21079010
TI  - Small cells--big future.

PMID- 21079011
TI  - How cell biologists can contribute to improving cancer outcomes.

PMID- 21079012
TI  - Cell biology: a love affair.

PMID- 21079013
TI  - Technological innovation leads to fundamental understanding in cell biology.

PMID- 21079014
TI  - Change, change, change: heeding the call.

PMID- 21079015
TI  - On force and function.

PMID- 21079016
TI  - The importance of being specified: cell fate decisions and their role in cell
      biology.

PMID- 21079017
TI  - Mechanistic biology in the next quarter century.

PMID- 21079018
TI  - Nature and nurture in the evolution of cell biology.

PMID- 21079019
TI  - Cell biology as a world view.

PMID- 21079020
TI  - Three quite different things that matter to me.

PMID- 21079021
TI  - It's the Technology, Stupid.

PMID- 21079022
TI  - Serendipity and cell biology.

PMID- 21079023
TI  - Cell biology redux.

PMID- 21079024
TI  - Remaining mysteries of the cytoplasm.

PMID- 21079025
TI  - How far will we see in the future?

PMID- 21079026
TI  - My dream of a fantastic voyage to see the inner workings of a cell.

PMID- 21079027
TI  - Seeing is believing: opportunities, challenges, and solutions in plant cell
      biology.

PMID- 21079028
TI  - Clathrin-mediated endocytosis: a universe of new questions.

PMID- 21079029
TI  - A richer and more diverse future for cell biology.

PMID- 21079030
TI  - Engineering the future with cell biology.

PMID- 21079031
TI  - It's all about the talent.

PMID- 21079032
TI  - Cell biology of tissues and tumors.

PMID- 21079033
TI  - The epistemology of cell biology.

PMID- 21079034
TI  - Mostly DNA, a bit of glucose, and the next 50 years.

PMID- 21079035
TI  - Seeing the yin and yang in cell biology.

PMID- 21079036
TI  - International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin
      receptor nomenclature, distribution, and function.
AB  - Kisspeptins are members of the Arg-Phe amide family of peptides, which have been
      identified as endogenous ligands for a G-protein-coupled receptor encoded by a
      gene originally called GPR54 (also known as AXOR12 or hOT7T175). After this
      pairing, the gene has been renamed KISS1R. The International Union of Basic and
      Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification
      recommends that the official name for the receptor is the kisspeptin receptor to
      follow the convention of naming the receptor protein after the endogenous ligand.
      The endogenous ligand was initially called metastin, after its role as a
      metastasis suppressor, and is now referred to as kisspeptin-54 (KP-54), a C
      terminally amidated 54-amino acid peptide cleaved from the 145-amino acid gene
      product. Shorter C-terminal cleavage fragments [KP-14, KP-13 and KP-10 (the
      smallest active fragment)] are also biologically active. Both receptor and
      peptide are widely expressed in human, rat, and mouse; the receptor sequence
      shares more than 80% homology in these species. Activation of the kisspeptin
      receptor by kisspeptin is via coupling to G(q/11) and the phospholipase C
      pathway, causing Ca(2+) mobilization. Mutations in the KISS1R gene result in
      hypogonadotropic hypogonadotropism, and targeted disruption of Kiss1r in mice
      reproduces this phenotype, which led to the discovery of the remarkable ability
      of the kisspeptin receptor to act as a molecular switch for puberty. In addition
      to regulating the reproductive axis, the kisspeptin receptor is also implicated
      in cancer, placentation, diabetes, and the cardiovascular system.

PMID- 21079037
TI  - International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid
      receptor nomenclature.
AB  - Lysophospholipids are cell membrane-derived lipids that include both
      glycerophospholipids such as lysophosphatidic acid (LPA) and sphingoid lipids
      such as sphingosine 1-phosphate (S1P). These and related molecules can function
      in vertebrates as extracellular signals by binding and activating G protein
      coupled receptors. There are currently five LPA receptors, along with a proposed
      sixth (LPA1-LPA6), and five S1P receptors (S1P1-S1P5). A remarkably diverse
      biology and pathophysiology has emerged since the last review, driven by cloned
      receptors and targeted gene deletion ("knockout") studies in mice, which
      implicate receptor-mediated lysophospholipid signaling in most organ systems and
      multiple disease processes. The entry of various lysophospholipid receptor
      modulatory compounds into humans through clinical trials is ongoing and may lead
      to new medicines that are based on this signaling system. This review
      incorporates IUPHAR Nomenclature Committee guidelines in updating the
      nomenclature for lysophospholipid receptors ( http://www.iuphar
      db.org/DATABASE/FamilyMenuForward?familyId=36).

PMID- 21079039
TI  - International Union of Basic and Clinical Pharmacology. LXXX. The class Frizzled
      receptors.
AB  - The receptor class Frizzled, which has recently been categorized as a separate
      group of G protein-coupled receptors by the International Union of Basic and
      Clinical Pharmacology, consists of 10 Frizzleds (FZD(1-10)) and Smoothened (SMO).
      The FZDs are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT)
      family, whereas SMO is indirectly activated by the Hedgehog (HH) family of
      proteins acting on the transmembrane protein Patched (PTCH). Recent years have
      seen major advances in our knowledge about these seven-transmembrane-spanning
      proteins, including: receptor function, molecular mechanisms of signal
      transduction, and the receptor's role in embryonic patterning, physiology,
      cancer, and other diseases. Despite intense efforts, many question marks and
      challenges remain in mapping receptor-ligand interaction, signaling routes,
      mechanisms of specificity and how these molecular details underlie disease and
      also the receptor's important role in physiology. This review therefore focuses
      on the molecular aspects of WNT/FZD and HH/SMO signaling discussing receptor
      structure, mechanisms of signal transduction, accessory proteins, receptor
      dynamics, and the possibility of targeting these signaling pathways
      pharmacologically.

PMID- 21079038
TI  - International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid
      receptors and their ligands: beyond CB1 and CB2.
AB  - There are at least two types of cannabinoid receptors (CB(1) and CB(2)). Ligands
      activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid
      Delta(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous
      compounds known as endocannabinoids. Cannabinoid receptor antagonists have also
      been developed. Some of these ligands activate or block one type of cannabinoid
      receptor more potently than the other type. This review summarizes current data
      indicating the extent to which cannabinoid receptor ligands undergo orthosteric
      or allosteric interactions with non-CB(1), non-CB(2) established GPCRs,
      deorphanized receptors such as GPR55, ligand-gated ion channels, transient
      receptor potential (TRP) channels, and other ion channels or peroxisome
      proliferator-activated nuclear receptors. From these data, it is clear that some
      ligands that interact similarly with CB(1) and/or CB(2) receptors are likely to
      display significantly different pharmacological profiles. The review also lists
      some criteria that any novel "CB(3)" cannabinoid receptor or channel should
      fulfil and concludes that these criteria are not currently met by any non-CB(1),
      non-CB(2) pharmacological receptor or channel. However, it does identify certain
      pharmacological targets that should be investigated further as potential CB(3)
      receptors or channels. These include TRP vanilloid 1, which possibly functions as
      an ionotropic cannabinoid receptor under physiological and/or pathological
      conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of
      CB(1) receptors to form heteromeric complexes with certain other GPCRs, 2)
      phylogenetic relationships that exist between CB(1)/CB(2) receptors and other
      GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB(1),
      non-CB(2) cannabinoid receptors; and 4) current cannabinoid receptor
      nomenclature.

PMID- 21079040
TI  - Prevention or modification of epileptogenesis after brain insults: experimental
      approaches and translational research.
AB  - Diverse brain insults, including traumatic brain injury, stroke, infections,
      tumors, neurodegenerative diseases, and prolonged acute symptomatic seizures,
      such as complex febrile seizures or status epilepticus (SE), can induce
      "epileptogenesis," a process by which normal brain tissue is transformed into
      tissue capable of generating spontaneous recurrent seizures. Furthermore,
      epileptogenesis operates in cryptogenic causes of epilepsy. In view of the
      accumulating information about cellular and molecular mechanisms of
      epileptogenesis, it should be possible to intervene in this process before the
      onset of seizures and thereby either prevent the development of epilepsy in
      patients at risk or increase the potential for better long-term outcome, which
      constitutes a major clinical need. For identifying pharmacological interventions
      that prevent, interrupt or reverse the epileptogenic process in people at risk,
      two groups of animal models, kindling and SE-induced recurrent seizures, have
      been recommended as potentially useful tools. Furthermore, genetic rodent models
      of epileptogenesis are increasingly used in assessing antiepileptogenic
      treatments. Two approaches have been used in these different model categories:
      screening of clinically established antiepileptic drugs (AEDs) for
      antiepileptogenic or disease-modifying potential, and targeting the key causal
      mechanisms that underlie epileptogenesis. The first approach indicated that among
      various AEDs, topiramate, levetiracetam, carisbamate, and valproate may be the
      most promising. On the basis of these experimental findings, two ongoing clinical
      trials will address the antiepileptogenic potential of topiramate and
      levetiracetam in patients with traumatic brain injury, hopefully translating
      laboratory discoveries into successful therapies. The second approach has
      highlighted neurodegeneration, inflammation and up-regulation of immune
      responses, and neuronal hyperexcitability as potential targets for
      antiepileptogenesis or disease modification. This article reviews these areas of
      progress and discusses the challenges associated with discovery of
      antiepileptogenic therapies.

PMID- 21079041
TI  - Allostery at G protein-coupled receptor homo- and heteromers: uncharted
      pharmacological landscapes.
AB  - For many years seven transmembrane domain G protein-coupled receptors (GPCRs)
      were thought to exist and function exclusively as monomeric units. However,
      evidence both from native cells and heterologous expression systems has
      demonstrated that GPCRs can both traffic and signal within higher-order
      complexes. As for other protein-protein interactions, conformational changes in
      one polypeptide, including those resulting from binding of pharmacological
      ligands, have the capacity to alter the conformation and therefore the response
      of the interacting protein(s), a process known as allosterism. For GPCRs,
      allosterism across homo- or heteromers, whether dimers or higher-order oligomers,
      represents an additional topographical landscape that must now be considered
      pharmacologically. Such effects may offer the opportunity for novel therapeutic
      approaches. Allosterism at GPCR heteromers is particularly exciting in that it
      offers additional scope to provide receptor subtype selectivity and tissue
      specificity as well as fine-tuning of receptor signal strength. Herein, we
      introduce the concept of allosterism at both GPCR homomers and heteromers and
      discuss the various questions that must be addressed before significant advances
      can be made in drug discovery at these GPCR complexes.

PMID- 21079044
TI  - Treating acute hypertension in the hospital: a Lacuna in the guidelines.

PMID- 21079046
TI  - Matrix metalloproteinases activities in hypertension: emerging opportunities.

PMID- 21079043
TI  - Drug-induced long QT syndrome.
AB  - The drug-induced long QT syndrome is a distinct clinical entity that has evolved
      from an electrophysiologic curiosity to a centerpiece in drug regulation and
      development. This evolution reflects an increasing recognition that a rare
      adverse drug effect can profoundly upset the balance between benefit and risk
      that goes into the prescription of a drug by an individual practitioner as well
      as the approval of a new drug entity by a regulatory agency. This review will
      outline how defining the central mechanism, block of the cardiac delayed
      rectifier potassium current I(Kr), has contributed to defining risk in patients
      and in populations. Models for studying risk, and understanding the way in which
      clinical risk factors modulate cardiac repolarization at the molecular level are
      discussed. Finally, the role of genetic variants in modulating risk is described.

PMID- 21079045
TI  - Association between placental morphology and childhood systolic blood pressure.
AB  - We tested hypotheses that disproportionately large placental size and vascular
      lesions were associated with high systolic blood pressure (SBP); and these
      associations might be more evident with age. The sample included 13 273 of 40 666
      full-term singletons in the Collaborative Perinatal Project. Placentas were
      examined by pathologists blinded of pregnancy courses and outcomes. The 4-month
      and 7-year SBPs were measured with palpation and auscultation methods,
      respectively. We found that placental weight (adjusted mean difference
      corresponding to an increase by 1 SD 0.50 [95% CI, 0.33 to 0.68]) and placenta
      fetus weight ratio (0.37 [95% CI, 0.19 to 0.54]) was positively associated with 7
      year SBP but not associated with 4-month SBP. Placental largest and smallest
      diameters and area were negatively associated with 4-month SBP but positively
      with 7-year SBP. Placental thickness was negatively associated with 4-month SBP
      only. Placental volume was negatively associated with 4-month SBP (-0.60 [95% CI,
      - 0.85 to -0.35]) but positively associated with 7-year SBP (0.48 [95% CI, 0.30
      to 0.67]). Thrombi in cord vessels (adjusted mean difference versus absence 2.73
      [95% CI, - 0.03 to 5.50]) and decidual vessels (2.58 [95% CI, 0.24 to 4.91]),
      villous microinfarcts (1.63 [95% CI, 0.71 to 2.55]), necrosis at the decidual
      margin (1.57 [95% CI, 0.54 to 2.59]), and basalis (3.44 [95% CI, 1.55 to 5.32])
      were associated with higher 4-month SBP only. We conclude that placental
      inefficiency, reflected by disproportionately large weight and size, predicts
      long-term blood pressure, whereas vascular resistance and lesions may only
      influence short-term blood pressure.

PMID- 21079048
TI  - MMP-2 mediates angiotensin II-induced hypertension under the transcriptional
      control of MMP-7 and TACE.
AB  - Development of cardiovascular disease induced by excessive Gq protein-coupled
      receptor agonist stimulation depends on signaling networks involving multiple
      matrix metalloproteinases (MMPs) and metalloproteinase disintegrins (ADAMs).
      Here, we hypothesized that MMP-2, being a major gelatinase in cardiac and
      vascular tissue, was likely to play a key role in cardiovascular homeostasis. We
      targeted MMP-2 using complementary and overlapping approaches involving
      pharmacological inhibition and RNA interference in mice treated with angiotensin
      II (1.4 mg/kg per day) for 12 days. We studied the development of hypertension
      (by tail cuff plethysmography), cardiac hypertrophy (by M-mode echocardiography,
      cardiomyocyte cross-sectional area, and quantitative real-time polymerase chain
      reaction (qRT-PCR) analysis of hypertrophy marker genes), and fibrosis (by
      picrosirius red collagen staining and qRT-PCR analysis of fibrosis marker genes)
      in mice receiving angiotensin II. We found that angiotensin II infusion
      upregulated MMP-2 concurrent with the development of hypertension, hypertrophy,
      and fibrosis. This upregulation of MMP-2 depended on MMP-7 and TACE (tumor
      necrosis factor-alpha convertase, ADAM-17). RNA interference targeting MMP-7 and
      TACE attenuated the angiotensin II-induced upregulation of MMP-2 and prevented
      the development of hypertension, as well as development of cardiac hypertrophy
      and fibrosis. In contrast, pharmacological inhibition and RNA interference of MMP
      2 attenuated angiotensin II-induced hypertension, without influencing development
      of cardiac hypertrophy or fibrosis. Downstream of MMP-7 and TACE, MMP-2 mediated
      angiotensin II-induced hypertension, but did not mediate cardiac hypertrophy or
      fibrosis. This suggests a functional specialization of MMP-2 in agonist-induced
      cardiovascular disease development that has potential implications for the design
      of metalloproteinase-based therapeutic strategies.

PMID- 21079047
TI  - Adenoviral delivery of VEGF121 early in pregnancy prevents spontaneous
      development of preeclampsia in BPH/5 mice.
AB  - An imbalance in circulating proangiogenic and antiangiogenic factors is
      postulated to play a causal role in preeclampsia (PE). We have described an
      inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome
      including late-gestational hypertension, proteinuria, and poor feto-placental
      outcomes. Here we tested the hypothesis that an angiogenic imbalance during
      pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this
      model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced
      levels of free vascular endothelial growth factor (VEGF) and placental growth
      factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked
      decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly,
      antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be
      the cause of this reduction, as sFLT1 levels were unchanged or even reduced in
      BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF(121) (Ad-VEGF)
      via tail vein at embryonic day 7.5 normalized both the plasma-free VEGF levels in
      BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad
      VEGF also reduced the incidence of fetal resorptions and prevented the late
      gestational spike in blood pressure and proteinuria observed in BPH/5. These data
      underscore the importance of dysregulation of angiogenic factors in the
      pathogenesis of PE and suggest the potential utility of early proangiogenic
      therapies in treating this disease.

PMID- 21079049
TI  - Predictive role of the nighttime blood pressure.
AB  - Numerous studies addressed the predictive value of the nighttime blood pressure
      (BP) as captured by ambulatory monitoring. However, arbitrary cutoff limits in
      dichotomized analyses of continuous variables, data dredging across selected
      subgroups, extrapolation of cross-sectional studies to prospective outcomes, and
      lack of comprehensive adjustments for confounders make interpretation of the
      literature difficult. We reviewed prospective studies with total mortality or a
      composite cardiovascular end point as an outcome in relation to the level and the
      circadian profile of systolic BP. We analyzed studies in hypertensive patients (n
      = 23 856) separately from those in individuals randomly recruited from
      populations (n = 9641). We pooled summary statistics and individual subject data,
      respectively. In both patients and populations, in analyses in which nighttime BP
      was additionally adjusted for daytime BP and vice versa, nighttime BP was a
      stronger predictor than daytime BP. With adjustment for the 24-hour BP, both the
      night-to-day BP ratio and dipping status remained significant predictors of
      outcome but added little prognostic value over and beyond the 24-hour BP level.
      In the absence of conclusive evidence proving that nondipping is a reversible
      risk factor, the option whether or not to restore the diurnal blood pressure
      profile to a normal pattern should be left to the clinical judgment of doctors
      and should be individualized for each patient. Current guidelines on the
      interpretation of ambulatory BP recording need to be updated.

PMID- 21079050
TI  - Remission in dermatitis herpetiformis: a cohort study.
AB  - OBJECTIVES: To determine the percentage of patients with dermatitis herpetiformis
      (DH) who experience at least 2 years of remission and to identify factors
      associated with DH remission. DESIGN: Retrospective cohort study. SETTING:
      National Institutes of Health (NIH). PATIENTS: Patients seen at the NIH during
      the 1972-2010 period who had clinical findings consistent with DH, whose normal
      skin showed the presence of granular IgA deposits at the dermoepidermal junction
      on direct immunofluorescence (DIF) examination, whose age of disease onset was
      known, who had DH for at least 2 years, and who were followed up for at least 3
      years after the initial NIH visit. MAIN OUTCOME MEASURE: Remission, defined as
      absence of skin lesions and symptoms of DH for more than 2 years while not taking
      sulfones (dapsone or sulfoxone), sulfapyridine, anti-tumor necrosis factor
      agents, or oral steroids and not adhering to a gluten-free diet. RESULTS: Among
      86 patients, in 10 (12%) the disease underwent remission (95% confidence
      interval, 6%-20%). Factors associated with DH remission included DH age of onset
      at 39 years or older vs onset at ages 8 to 38 years (unadjusted P = .02; adjusted
      P = .07) and DH onset year between 1960 and 1972 vs onset between 1935 and 1959
      or after 1972 (P = .02 for global comparison of 4 onset-year groups).
      CONCLUSIONS: Dermatitis herpetiformis can go into remission. Clinicians should
      attempt to wean patients with well-controlled DH from a gluten-free diet and/or
      use of sulfones or other therapies to determine if the DH might have remitted.
      Our findings provide insight into the pathogenesis and course of this disease and
      may serve to guide long-term management of patients with DH.

PMID- 21079042
TI  - Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in
      human diseases.
AB  - Polymorphonuclear neutrophils are the first cells recruited to inflammatory sites
      and form the earliest line of defense against invading microorganisms. Neutrophil
      elastase, proteinase 3, and cathepsin G are three hematopoietic serine proteases
      stored in large quantities in neutrophil cytoplasmic azurophilic granules. They
      act in combination with reactive oxygen species to help degrade engulfed
      microorganisms inside phagolysosomes. These proteases are also externalized in an
      active form during neutrophil activation at inflammatory sites, thus contributing
      to the regulation of inflammatory and immune responses. As multifunctional
      proteases, they also play a regulatory role in noninfectious inflammatory
      diseases. Mutations in the ELA2/ELANE gene, encoding neutrophil elastase, are the
      cause of human congenital neutropenia. Neutrophil membrane-bound proteinase 3
      serves as an autoantigen in Wegener granulomatosis, a systemic autoimmune
      vasculitis. All three proteases are affected by mutations of the gene (CTSC)
      encoding dipeptidyl peptidase I, a protease required for activation of their
      proform before storage in cytoplasmic granules. Mutations of CTSC cause Papillon
      Lefevre syndrome. Because of their roles in host defense and disease, elastase,
      proteinase 3, and cathepsin G are of interest as potential therapeutic targets.
      In this review, we describe the physicochemical functions of these proteases,
      toward a goal of better delineating their role in human diseases and identifying
      new therapeutic strategies based on the modulation of their bioavailability and
      activity. We also describe how nonhuman primate experimental models could assist
      with testing the efficacy of proposed therapeutic strategies.

PMID- 21079051
TI  - Melanoma quality of life: pilot study using utility measurements.

PMID- 21079052
TI  - Congenital epidermolysis bullosa acquisita: vertical transfer of maternal
      autoantibody from mother to infant.
AB  - BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare, chronic, autoimmune
      bullous dermatosis that is caused by autoantibodies against the noncollagenous
      terminus of the alpha chain of type VII collagen, resulting in decreased
      anchoring fibrils in the lamina densa. It classically presents with skin
      fragility and trauma-induced blisters that are particularly extensive over the
      distal aspect of the extremities and that heal with milia, dyspigmentation, and
      scarring, similar in presentation to dystrophic epidermolysis bullosa. Disease
      onset is typically in adulthood, although rare cases of childhood disease occur.
      To our knowledge, a case involving a neonate with congenital EBA has not yet been
      reported in the literature. We describe a newborn with transient EBA due to the
      passive transfer of maternal autoantibodies. OBSERVATIONS: A 2-day-old girl was
      evaluated for tense blisters and areas of denuded skin that had been present
      since birth. Her mother carried the diagnosis of EBA. The results of
      histopathologic analysis, immunofluorescence studies, and enzyme-linked
      immunosorbent assay confirmed the diagnosis of neonatal EBA. The patient improved
      with supportive therapy and has not required systemic intervention. CONCLUSIONS:
      Autoimmune neonatal bullous skin disease caused by placental transfer of maternal
      IgG autoantibodies is rare. It has been reported in neonates born to mothers with
      pemphigus vulgaris, pemphigus foliaceus, and gestational pemphigoid. To our
      knowledge, congenital EBA has not been previously reported. Vertically acquired
      congenital autoimmune blistering disorders appear to be self-limited and resolve
      with supportive therapy, concomitant with the presumed clearance of maternal
      autoantibodies from the neonate's circulation.

PMID- 21079053
TI  - Nonspecific capillary proliferation and vasculopathy indicate skin hypoxia in
      erythromelalgia.
AB  - OBJECTIVE: To report on the histopathologic findings of affected skin in
      consecutively collected biopsy specimens from 49 patients with erythromelalgia
      (EM). DESIGN: Skin biopsy specimens were obtained from the foot arch and analyzed
      by light microscopy, immunofluorescence microscopy, and electron microscopy.
      SETTING: Oslo University Hospital-Gaustad, University of Oslo, Oslo, Norway.
      PARTICIPANTS: Thirty-one patients had primary EM, 17 patients had secondary EM,
      and 1 patient had erythromelalgic syndrome. MAIN OUTCOME MEASURE: Evidence of
      microvascular abnormalities in skin biopsy specimens. RESULTS: Light microscopy
      showed evidence of capillary proliferation in 10 of 31 patients with primary EM
      and in 1 of 17 patients with secondary EM. The biopsy specimen from the patient
      with erythromelalgic syndrome showed numerous capillary nests with endothelial
      cell defects and a slight perivascular inflammatory reaction. Among the 17
      secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in
      the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1
      patient with diabetes mellitus. Eleven patients also had signs of vasculopathy
      based on findings of immunodeposits of C3 and fibrin. Six of 30 patients with
      primary EM showed endothelial abnormalities on electron microscopy. All 3
      investigations showed unremarkable biopsy results in 16 cases. CONCLUSIONS:
      Histopathologic analysis is not useful as a routine diagnostic tool in EM because
      no morphological changes are specific to EM. The capillary proliferation and
      vasculopathy are assumed to be a consequence of intermittent skin hypoxia
      (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence
      of EM or a pathogenic factor in the development of the disease is uncertain.

PMID- 21079054
TI  - Is ticagrelor the antiplatelet therapy panacea?

PMID- 21079055
TI  - First analysis of the relation between CYP2C19 genotype and pharmacodynamics in
      patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND
      genotype studies.
AB  - BACKGROUND: The influence of cytochrome P450 (CYP) 2C19 genotype on platelet
      function in patients treated with ticagrelor versus clopidogrel is unknown.
      METHODS AND RESULTS: CYP2C19 (*1, *2, *3, *4, *5, *6, *7, *8, *17) genotyping was
      performed in patients with coronary artery disease treated with ticagrelor (180
      mg load, 90 mg BID) (n=92) or clopidogrel (600-mg load, 75 mg/d) (n=82). All
      patients received 75 to 100 mg/d aspirin. Platelet function was measured by
      aggregometry, VerifyNow P2Y12 assay, and vasodilator-stimulated phosphoprotein
      phosphorylation assay at predose, 8 hours postloading, and maintenance. In each
      treatment group, patients were categorized according to 2C19 genotype carrier
      status (loss-of-function, gain-of-function) and metabolizer status. Kruskal
      Wallis test was used to compare platelet function among these categories for each
      treatment, and Wilcoxon rank sum test was used to compare platelet function
      between the clopidogrel and ticagrelor groups for each category. There was no
      statistically significant influence of genotype on platelet function during
      aspirin therapy alone. Ticagrelor exhibited lower platelet reactivity than
      clopidogrel by all assays irrespective of 2C19 genotype or metabolizer status
      (P<0.01). Loss-of-function carriers had greater platelet reactivity during
      clopidogrel therapy. The influence of genotype on platelet reactivity was
      greatest during clopidogrel maintenance and best demonstrated by the VerifyNow
      P2Y12 assay. CONCLUSIONS: This report is the first to demonstrate the superior
      pharmacodynamic effect of ticagrelor compared with clopidogrel irrespective of
      CYP2C19 genotype. Whereas CYP2C19 genotype influenced the antiplatelet effect of
      clopidogrel, there was no effect of CYP2C19 genotype during ticagrelor therapy.

PMID- 21079056
TI  - Inexpensive solution for habit-tic deformity.

PMID- 21079057
TI  - Uncertainty in the perioperative management of high-risk cutaneous squamous cell
      carcinoma among Mohs surgeons.
AB  - OBJECTIVE: To evaluate whether Mohs surgeons' management of high-risk cutaneous
      squamous cell carcinoma (HRCSCC) is uniform regarding radiologic nodal staging
      (RNS) and adjuvant radiation therapy (ART). DESIGN: A survey study of randomly
      selected, fellowship-trained Mohs surgeons. SETTING: An academic medical center.
      PARTICIPANTS: American College of Mohs Surgery members who responded to an e-mail
      invitation completed either a survey regarding management of HRCSCC (n=117) or
      SCC with perineural invasion (PNI) (n=118). Participants totaled approximately
      25% of the American College of Mohs Surgery membership. MAIN OUTCOME MEASURES:
      (1) Percentage of patients with HRCSCC referred for RNS, sentinel lymph node
      biopsy (SLNB), or ART over the preceding 12 months; (2) top factors leading
      surgeons to consider RNS, SLNB, or ART; and (3) acceptance of ART for clinical
      scenarios of various degrees of PNI. RESULTS: Most respondents cited PNI and in
      transit metastasis as top factors leading to consideration of RNS, SLNB, or ART.
      Otherwise, there was no consensus regarding use of, or indications for, RNS,
      SLNB, or ART. CONCLUSIONS: The lack of consistency between experts indicates that
      there is equipoise regarding indications for RNS and ART in HRCSCC. There is also
      wide variation in RNS and ART practices among Mohs surgeons who are specifically
      trained to manage HRCSCC. Clinical trials should therefore be conducted in these
      areas as there is no clear standard of care.

PMID- 21079058
TI  - Uncertainty and variance in the management of high-risk cutaneous squamous cell
      carcinoma: comment on "Uncertainty in the perioperative management of high-risk
      cutaneous squamous cell carcinoma among Mohs surgeons".

PMID- 21079059
TI  - Early white discoloration of infantile hemangioma: a sign of impending
      ulceration.
AB  - OBJECTIVE: To evaluate the relationship between early white discoloration of
      infantile hemangioma (IH) and ulceration. DESIGN: Retrospective cohort study.
      SETTING: Tertiary referral center. PATIENTS: A case series of 11 infants with
      early white discoloration of IH are described. An additional 55 infants with IH,
      aged 3 months, were evaluated retrospectively from a photograph archive to
      further explore the relationship between early white discoloration and presence
      or development of ulceration. MAIN OUTCOME MEASURES: Patient demographics and
      hemangioma size, location, and subtype are documented. Sensitivity and
      specificity of white discoloration in relationship to ulceration are estimated.
      RESULTS: Ten of the 11 infants in the case series were girls (90%); all IHs were
      of segmental or indeterminate subtype. Average age at first ulceration was 2.6
      months, with average age at healing 5.2 months. No intervention halted
      progression of ulceration. Of the 55 additional 3-month-old infants, 14 had white
      discoloration and 12 of these 14 had or developed ulceration (86%). When the
      hemangioma was either white or slightly white, sensitivity for predicting
      ulceration was 1.00 (95% confidence interval [CI], 0.78-1.00), with a specificity
      of 0.68 (95% CI, 0.51-0.81). In contrast, in infants with either slightly white
      or no white discoloration, the sensitivity for not developing ulceration was 0.80
      (95% CI, 0.52-0.96), with a specificity of 0.95 (95% CI, 0.83-0.99), suggesting
      that a lack of substantial white discoloration early in infancy indicates low
      risk of ulceration. CONCLUSION: Early white discoloration of infantile hemangioma
      is highly suggestive of impending ulceration.

PMID- 21079061
TI  - Counseling patients about sun protection related to an active outdoor life:
      comment on "environmental cues to ultraviolet radiation and personal sun
      protection in outdoor winter recreation".

PMID- 21079060
TI  - Environmental cues to UV radiation and personal sun protection in outdoor winter
      recreation.
AB  - OBJECTIVE: To predict the prevalence of UV radiation (hereinafter, UV) at North
      American ski resorts using temporal, seasonal, altitudinal, and meteorological
      factors and associate UV with a set of adult sun protection behaviors. DESIGN:
      Ultraviolet radiation observations and cross-sectional survey of adults on sun
      protection were collected. SETTING: Data were collected at 32 high-altitude ski
      areas located in western North America from 2001 through 2003. PARTICIPANTS: The
      sample consisted of 3937 adult skiers or snowboarders. MAIN OUTCOME MEASURES:
      Measurements of direct, reflected, and diffuse UV were performed at 487
      measurement points using handheld meters and combined with self-reported and
      observed sun protection assessed for adults interviewed on chairlifts. RESULTS:
      The strongest predictors of UV were temporal proximity to noon, deviation from
      winter solstice, and clear skies. By contrast, altitude and latitude had more
      modest associations with UV and temperature had a small positive relationship
      with UV. Guest sun safety was inconsistently associated with UV: UV was
      positively related to adults wearing more sunscreen, reapplying it after 2 hours,
      and wearing protective eyewear, but fewer adults exhibited many of the other sun
      protection behaviors, such as wearing hats and protective clothing or using lip
      balm, on days when UV was elevated. Guests took more sun safety precautions on
      clear-sky days but took steps to maintain body warmth on inclement days.
      CONCLUSIONS: In future sun safety promotions, adults should be encouraged to wear
      sunscreen on cloudy days because UV is still high and conditions can change
      rapidly. They need reminders to rely more on season and time of day when judging
      UV and the need for sun safety.

PMID- 21079062
TI  - The association of bullous pemphigoid with cerebrovascular disease and dementia:
      a case-control study.
AB  - OBJECTIVE: To investigate the relationship between bullous pemphigoid (BP) and
      neurologic disease. DESIGN: Case-control study. SETTING: Tertiary care center for
      immunobullous diseases and skin tumor clinics at a university hospital in Oxford,
      England. PARTICIPANTS: Ninety consecutive patients with BP and 141 controls. MAIN
      OUTCOME MEASURES: Age-adjusted prevalence of neurologic disease in patients and
      controls. Time interval between the diagnosis of neurologic disease and BP and
      type of associated neurologic disease. RESULTS: At least 1 neurologic diagnosis
      was present in 42 patients (46%) compared with 16 controls (11%). Patients had
      significantly increased odds for neurologic diseases regardless of age and sex
      (crude odds ratio [OR], 6.8; 95% confidence interval [CI], 3.5-13.3; adjusted OR,
      6.2; 95% CI, 3.1-12.4). Four major neurologic diagnoses were observed
      (cerebrovascular disease, dementia, Parkinson disease, and epilepsy), with
      statistical significance for cerebrovascular disease and dementia (crude OR for
      cerebrovascular disease, 6.3; 95% CI, 2.8-14.2; adjusted OR, 6.0; 95% CI, 2.6
      13.6; crude OR for dementia, 10.7; 95% CI, 2.3-49.0; adjusted OR, 7.9; 95% CI,
      1.7-37.3). When accurate data on time of onset of neurologic disease were present
      (36 of 42 patients [85%]), BP followed neurologic disease in most patients (26 of
      36 patients [72%]), with a median interval of 5.5 years. CONCLUSION: Bullous
      pemphigoid is significantly associated with cerebrovascular disease and dementia.

PMID- 21079063
TI  - Dermoscopic island: a new descriptor for thin melanoma.
AB  - OBJECTIVES: To determine the frequency and the features of the dermoscopic island
      (DI) in melanocytic lesions and to assess its specificity for the diagnosis of
      melanoma. Dermoscopy improves the diagnostic accuracy of melanoma, but only a few
      dermoscopic descriptors specific for thin melanomas have been identified. We
      defined a new descriptor, the dermoscopic island, a well-circumscribed area
      showing a uniform dermoscopic pattern that differs from the rest of the pigmented
      lesion. DESIGN: Dermoscopic images of 96 in situ melanomas, 266 invasive
      melanomas, and 612 dermoscopic atypical nevi were evaluated to establish the
      presence and the main pattern of the DI. Also, clinical and histologic
      characteristics were analyzed. SETTING: Dermoscopic images were collected from
      lesions excised between 2003 and 2008 at the Department of Dermatology,
      University of Modena and Reggio Emilia. MAIN OUTCOME MEASURES: Specificity and
      odds ratio for melanoma; dermoscopic and histologic characteristics of lesions
      with a DI. RESULTS: The DI was present in 10.4% of in situ melanomas, 4.1% of
      invasive melanomas, and 3.1% of dermoscopic atypical nevi. The odds ratio for
      melanoma was 1.922, and specificity was 96.9%. Invasive melanomas with a DI were
      thinner than those lacking this descriptor. In addition, more than half of the
      melanomas with a DI arose on a nevus. The DI appeared mainly reticular on a
      reticular background. CONCLUSION: The DI is characteristic of thin melanoma
      arising in a nevus; thus, it can be considered a potential early sign of
      transformation of a nevus into a melanoma.

PMID- 21079064
TI  - Hidradenitis suppurativa and concomitant pyoderma gangrenosum: a case series and
      literature review.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) are both
      rare inflammatory skin conditions that are associated with systemic inflammatory
      diseases. We performed a retrospective medical chart review of patients with an
      overlap of HS and PG. OBSERVATIONS: We identified 11 cases of PG lesions
      presenting in patients with HS. Ten of the patients were women, and 9 were obese.
      All the patients developed HS lesions first, a median of 2.5 years (range, 0-15
      years) preceding the appearance of PG lesions. All patients required multiple
      therapeutic agents because their diseases were often poorly responsive to
      standard therapies. Two patients received tumor necrosis factor inhibitors; 1
      responded to treatment. One patient was treated with anakinra (interleukin-1
      receptor antagonist) and had a 75% improvement of her lesions. CONCLUSIONS: We
      have identified a group of patients who have an overlap of PG and HS. Pyoderma
      gangrenosum can appear at any point after the development of HS and often has a
      severe, refractory course. We propose that PG and HS may represent variant
      manifestations of cytokine dysregulation by the innate immune system with common
      etiology. New therapeutic agents are eagerly sought, and further investigation
      with regard to interleukin 1 blockade is warranted.

PMID- 21079065
TI  - Thyrotoxicosis with pegylated interferon alfa-2b.
AB  - BACKGROUND: Despite adequate surgery, a diagnosis of stage III melanoma carries a
      high risk of relapse, and hence mortality. Interferon alfa is the only treatment
      that has currently been shown to alter the natural history of the disease,
      delaying relapse-free survival, particularly in patients with micrometastatic
      disease. There is also recent evidence of a prognostic advantage conferred by the
      development of autoimmune conditions in patients receiving adjuvant interferon
      therapy. OBSERVATIONS: We present the case of a 27-year-old woman with stage IIIa
      melanoma who was entered into the European Organisation for the Research and
      Treatment of Cancer 18991 trial of 5-year adjuvant treatment with pegylated
      interferon (peginterferon) alfa-2b. The patient developed thyrotoxicosis 3 months
      after commencing treatment, which required treatment with propylthiouracil. The
      degree of thyrotoxicosis corresponded closely to the dose of peginterferon alfa
      2b given. However, in this patient, the hyperthyroidism resolved spontaneously
      after 4 years when peginterferon treatment was still ongoing. Seven years
      following the initial diagnosis, the patient has not had disease relapse.
      CONCLUSION: Hyperthyroidism is less common than hypothyroidism as a consequence
      of interferon therapy, and this case is atypical in that it resolved
      spontaneously during interferon therapy but is in accordance with the recent
      evidence of a positive association between interferon-associated autoimmunity and
      prognosis.

PMID- 21079066
TI  - "Bullfrog neck," a unique morphologic trait in HIV lipodystrophy: case series and
      review of the literature.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-associated lipodystrophy is a
      syndrome that occurs primarily in individuals who are being treated with highly
      active antiretroviral therapy (HAART). OBSERVATIONS: We describe 3 patients with
      an 8- to 15-year history of HIV disease and HAART who presented a unique feature
      of HIV lipodystrophy, the "bullfrog neck." In addition to their features of
      facial lipoatrophy and "buffalo hump," patients had the unique feature of
      circumferential enlargement of the neck. All patients were undergoing treatment
      with the same non-nucleoside reverse-transcriptase inhibitor (NRTI) medication,
      efavirenz. CONCLUSIONS: We present a novel finding of the bullfrog neck in 3
      patients with classic features of HIV lipodystrophy. The dysmorphic features of
      HIV lipodystrophy present a significant therapeutic challenge because the current
      repertoire of treatments is only modestly effective, and the disease in patients
      who continue HAART regimens over the long term will progress. Review of the
      recent literature suggests that the individual protease inhibitors and NRTIs used
      may play a role in the development and progression of HIV lipodystrophy.

PMID- 21079067
TI  - Specific nail alterations in cutaneous T-cell lymphoma: successful treatment with
      topical mechlorethamine.
AB  - BACKGROUND: Cutaneous T-cell lymphoma can be associated with clinically
      significant nail alterations, the presentation of which can be protean and
      misleading. To date, only a few reports have demonstrated direct specific tumor
      infiltration of the nail bed, while little is known about the efficacy of topical
      treatments. OBSERVATIONS: We describe the case of a 93-year-old man presenting
      with Sezary syndrome who developed clinically significant nail alterations. Light
      microscopy studies and T-cell receptor rearrangement analysis demonstrated the
      presence of a specific lymphocytic infiltrate within the nail bed. The patient
      was given repeated courses of topical mechlorethamine, leading to a sustained
      complete remission of both skin and nail alterations. CONCLUSIONS: Specific nail
      involvement should be recognized and considered in all patients with cutaneous T
      cell lymphomas. Topical mechlorethamine remains an attractive therapeutic option
      in cases of specific nail alterations, especially for situations in which
      systemic therapies are either not indicated or unlikely to be well tolerated.

PMID- 21079069
TI  - Defining, treating, and studying very high-risk cutaneous squamous cell
      carcinomas.

PMID- 21079070
TI  - Characteristics of infantile hemangiomas as clues to pathogenesis: does hypoxia
      connect the dots?

PMID- 21079072
TI  - Flagellate dermatitis. Shiitake dermatitis (toxicoderma).

PMID- 21079073
TI  - Multiple brown patches on the trunk. Idiopathic eruptive macular pigmentation
      with papillomatosis (IEMP).

PMID- 21079074
TI  - Rapidly enlarging mass on the leg develops after local trauma. Trauma-induced
      secondary cutaneous plasmacytoma (TISP).

PMID- 21079075
TI  - Chronic indurated gingival ulceration. Bisphosphonate-related osteonecrosis of
      the jaw (BRONJ).

PMID- 21079076
TI  - The utility of clinical photographs in dermatopathologic diagnosis: a survey
      study.

PMID- 21079077
TI  - Practice gaps--Submitting clinical photographs to dermatopathologists to
      facilitate interpretations: comment on "the utility of clinical photographs in
      dermatopathologic diagnosis: a survey study".

PMID- 21079078
TI  - Lentiginous melanoma in situ treatment with topical imiquimod: need for
      individualized regimens.

PMID- 21079079
TI  - Botulinum toxin type a headache treatment and entrapment of the supratrochlear
      nerve.

PMID- 21079080
TI  - Diffuse dermal angiomatosis arising in cutis marmorata telangiectatica congenita.

PMID- 21079081
TI  - Hepatoerythropoietic porphyria and familial porphyria cutanea tarda in Spanish
      patients: G281E mutation in the uroporphyrinogen decarboxylase gene.

PMID- 21079082
TI  - Botulinum toxin A treatment for hyperhidrosis in patients with prosthetic limbs.

PMID- 21079083
TI  - Ustekinumab for rapid treatment of nail psoriasis.

PMID- 21079084
TI  - Multiple desmoplastic melanomas in Birt-Hogg-Dube syndrome and a proposed
      signaling link between folliculin, the mTOR pathway, and melanoma susceptibility.

PMID- 21079085
TI  - Localized porokeratosis secondary to ionizing radiotherapy for prostate
      carcinoma.

PMID- 21079086
TI  - Levamisole-induced cutaneous necrosis mimicking coagulopathy.

PMID- 21079087
TI  - Dermoscopy of pityriasis lichenoides et varioliformis acuta.

PMID- 21079088
TI  - Surgical residency training in transition: evolution or revolution?

PMID- 21079089
TI  - Young dinosaurs fighting extinction.

PMID- 21079090
TI  - Tread carefully with stepwise regression.

PMID- 21079091
TI  - Timing of intubation and ventilator-associated pneumonia following injury.
AB  - HYPOTHESIS: In an emergency medical system with established rapid-sequence
      intubation protocols, prehospital (PH) intubation of patients with trauma is not
      associated with a higher rate of ventilator-associated pneumonia (VAP) than
      emergency department (ED) intubation. DESIGN: Retrospective observational cohort.
      SETTING: Level I trauma center. PATIENTS: Adult patients with trauma intubated in
      a PH or an ED setting from July 1, 2007, through July 31, 2008. MAIN OUTCOME
      MEASURES: Diagnosis of VAP by means of bronchoscopic alveolar lavage or clinical
      assessment when bronchoscopic alveolar lavage was impossible. Secondary outcomes
      included time to VAP, length of hospitalization, and in-hospital mortality.
      RESULTS: Of 572 patients, 412 (72.0%) underwent PH intubation. The ED group was
      older than the PH group (mean ages, 46.4 vs 39.1 years; P < .001) and had a
      higher incidence of blunt injury (142 [88.8%] vs 322 [78.2%]; P = .002). The mean
      (SD) lowest recorded ED systolic blood pressure was lower in the ED group (102.8
      [1.9] vs 111.4 [1.2] mm Hg; P < .001), despite similar mean injury severity
      scores in both groups (27.2 [0.7] vs 27.0 [1.1]; P = .94). There was no
      difference in the mean rate of VAP (30 [18.8%] vs 71 [17.2%]; P = .66) or mean
      time to diagnosis (8.1 [1.2] vs 7.8 [1.0] days; P = .89). Logistic regression
      analysis identified history of drug abuse, lowest recorded ED systolic blood
      pressure, and injury severity score as 3 independent factors predictive of VAP.
      CONCLUSIONS: Prehospital intubation of patients with trauma is not associated
      with higher risk of VAP. Further investigation of intubation factors and the
      incidence and timing of aspiration is required to identify potentially modifiable
      factors to prevent VAP.

PMID- 21079092
TI  - Variability in pediatric splenic injury care: results of a national survey of
      general surgeons.
AB  - BACKGROUND: Although nonoperative management is the standard of care for
      hemodynamically stable children with blunt splenic trauma, significant variation
      in practice exists. Little attention has been given to physician factors
      associated with management differences. DESIGN: Nationally representative mail
      survey conducted in June 2008. SETTING: United States. PARTICIPANTS: Ten percent
      random sample of active, dues-paying fellows in the American College of Surgeons.
      MAIN OUTCOME MEASURES: Knowledge, attitudes, and beliefs toward pediatric splenic
      injury management, including the role of clinical practice guidelines. RESULTS:
      Almost all of the 375 responding surgeons (97.4%) agreed that surgical
      intervention is not immediately necessary for hemodynamically stable children.
      However, surgeons reported significant disagreement regarding whether blood
      should be administered before operative intervention for hemodynamically unstable
      children and whether explorative surgery is needed for stable patients with
      evidence of contrast extravasation on computed tomography. Only 18.7% of surgeons
      reported being very familiar with the clinical practice guidelines for the
      management of pediatric blunt splenic trauma from either the Eastern Association
      for the Surgery of Trauma or the American Pediatric Surgical Association.
      Surgeons who were very familiar with either guideline were significantly more
      likely to rate the guidelines as beneficial (90.0% vs 72.8%, P = .002).
      CONCLUSIONS: General surgeons reported varying degrees of familiarity with and
      use of clinical practice guidelines for pediatric splenic injury management.
      Limited pediatric experience and lack of pediatric hospital resources may limit
      more widespread adoption of nonoperative management. Targeted educational
      interventions may help increase surgeon knowledge of guidelines and best
      practices.

PMID- 21079094
TI  - Reoperative parathyroidectomy: location of missed glands based on a contemporary
      nomenclature system.
AB  - OBJECTIVES: To evaluate and categorize the locations of missed parathyroid glands
      found during reoperative parathyroidectomy and to determine any factors
      associated with these locations. DESIGN: Retrospective cohort study. SETTING:
      Tertiary referral center. PATIENTS: Fifty-four patients who underwent reoperative
      parathyroidectomy for persistent or recurrent hyperparathyroidism from January 1,
      2005, through January 1, 2009. MAIN OUTCOME MEASURES: Location of missed
      parathyroid glands and their association with continuous variables were analyzed
      using a Kruskal-Wallis test, and associations between gland location and
      categorical variables were evaluated using the Fisher exact test. RESULTS: Among
      54 patients, 50 abnormal parathyroid glands were identified, resected, and
      classified as follows: 5 (10%) were type A (adherent to the posterior thyroid
      capsule); 11 (22%), type B (behind the thyroid in the tracheoesophageal groove);
      7 (14%), type C (close to the clavicle in the prevertebral space); 3 (6%), type D
      (directly over the recurrent laryngeal nerve); 9 (18%), type E (easy to identify;
      near the inferior thyroid pole); 13 (26%), type F (fallen into the thymus); and 2
      (4%), type G (gauche, within the thyroid gland). No demographic, biochemical, or
      pathological factors were significantly associated with gland location. Among the
      43 patients followed up for 6 months, 40 (93%) had documented cures. CONCLUSIONS:
      Missed glands after parathyroidectomy for hyperparathyroidism can be found in
      standard locations in most cases. A standardized nomenclature system based on the
      regional anatomy and the embryology of the parathyroid glands can guide a
      systematic exploration for parathyroid adenomas that are not easily identified
      and facilitate communication about gland locations.

PMID- 21079093
TI  - Risk factors for lymphedema in a prospective breast cancer survivorship study:
      the Pathways Study.
AB  - OBJECTIVE: To determine the incidence of breast cancer-related lymphedema (BCRL)
      during the early survivorship period as well as demographic, lifestyle, and
      clinical factors associated with BCRL development. DESIGN: The Pathways Study, a
      prospective cohort study of breast cancer survivors with a mean follow-up time of
      20.9 months. SETTING: Kaiser Permanente Northern California medical care program.
      PARTICIPANTS: We studied 997 women diagnosed from January 9, 2006, through
      October 15, 2007, with primary invasive breast cancer and who were at least 21
      years of age at diagnosis, had no history of any cancer, and spoke English,
      Spanish, Cantonese, or Mandarin. MAIN OUTCOME MEASURE: Clinical indication for
      BCRL as determined from outpatient or hospitalization diagnostic codes,
      outpatient procedural codes, and durable medical equipment orders. RESULTS: A
      clinical indication for BCRL was found in 133 women (13.3%), with a mean time to
      diagnosis of 8.3 months (range, 0.7-27.3 months). Being African American (hazard
      ratio, 1.93; 95% confidence interval, 1.00-3.72) or more educated (P for trend =
      .03) was associated with an increased risk of BCRL. Removal of at least 1 lymph
      node (hazard ratio, 1.04; 95% confidence interval, 1.02-1.07) was associated with
      an increased risk, yet no significant association was observed for type of lymph
      node surgery. Being obese at breast cancer diagnosis was suggestive of an
      elevated risk (hazard ratio, 1.43; 95% confidence interval, 0.88-2.31).
      CONCLUSIONS: In a large cohort study, BCRL occurs among a substantial proportion
      of early breast cancer survivors. Our findings agree with those of previous
      studies on the increased risk of BCRL with removal of lymph nodes and being
      obese, but they point to a differential risk according to race or ethnicity.

PMID- 21079095
TI  - Simple measurement of intra-abdominal fat for abdominal surgery outcome
      prediction.
AB  - OBJECTIVE: To assess the effect of increasing body mass index, intra-abdominal
      fat, and outer abdominal fat on outcome in patients undergoing major hepatectomy.
      DESIGN: Cohort study. SETTING: Memorial Sloan-Kettering Cancer Center.
      PARTICIPANTS: We studied patients aged 19 to 86 years undergoing major hepatic
      resection between June 18, 1996, and November 6, 2001. Complications were
      extracted from a prospective database at a tertiary cancer center. INTERVENTION:
      A total of 349 patients were grouped according to body mass index for analysis.
      Preoperative abdominal computed tomographic scans were examined and measurements
      of perinephric fat (as a surrogate for intra-abdominal fat) and outer abdominal
      fat taken at uniform anatomical locations. MAIN OUTCOME MEASURES: We compared 30
      day mortality and morbidity figures, length of stay, and operating times.
      RESULTS: Body mass index had an influence on operative time (P = .02) but no
      significant effect on mortality, frequency of any complications, frequency of
      severe complications, or length of stay (P = .80, P = .89, P = .16, and P = .81,
      respectively). Outer abdominal fat had no significant effect on any of the 5
      outcome measures. Perinephric fat measurements had a significant effect on most
      outcome measures (P = .004 for mortality, P = .003 for frequence of
      complications, P < .001 for frequence of severe complications, and P = .001 for
      length of stay). CONCLUSIONS: Outer appearances of obesity do not correlate with
      poor outcomes for major upper abdominal operations. A simple measurement of
      perinephric fat, as a surrogate for intra-abdominal fat, on preoperative imaging
      gives a more useful risk assessment for patients undergoing major upper abdominal
      operations.

PMID- 21079096
TI  - Prediction of mortality rate after major hepatectomy in patients without
      cirrhosis.
AB  - OBJECTIVE: To assess the ability of preoperative biological parameters to predict
      a fatal outcome after a major liver resection in patients without cirrhosis.
      DESIGN: Retrospective descriptive cohort study. SETTING: Department of Digestive
      Surgery and Transplantation, University of Strasbourg. PATIENTS: From January 1,
      2004, through December 31, 2007, 67 consecutive patients underwent resection of
      at least 4 contiguous liver segments. MAIN OUTCOME MEASURES: Perioperative data
      were prospectively recorded, and predictors of postoperative mortality rate and
      liver failure were analyzed. RESULTS: Five patients (7%) died after a mean (SD)
      of 32.4 (11.8) postoperative days. The overall morbidity was 73% (49 patients).
      Univariate analysis revealed that a preoperative alanine aminotransferase blood
      level greater than 40 U/L (to convert to microkatals per liter, multiply by
      0.0167), a preoperative prothrombin ratio less than 70%, a preoperative
      Indocyanine green retention rate at 15 minutes of greater than 15%, preoperative
      biliary drainage, and performance of extrahepatic bile duct resection
      significantly predict the occurrence of in-hospital death. The number of
      preoperative biological parameters in each patient significantly increased the
      mortality rate. Indeed, the mortalities were 0%, 3%, and 67% in patients
      presenting with none, 1, and 2 or more risk factors, respectively. CONCLUSIONS:
      This study shows that preoperative liver tests and function can predict
      postoperative fatal outcome in patients presenting with biliary carcinomas and
      requiring a major liver resection. On the basis of these preoperative biological
      parameters, a decision-making algorithm is provided.

PMID- 21079097
TI  - Risk factors and outcomes for foreign body left during a procedure: analysis of
      413 incidents after 1 946 831 operations in children.
AB  - OBJECTIVE: To determine risk factors and outcomes associated with a foreign body
      left during a procedure in a population of pediatric surgical patients. DESIGN:
      Case-control study. SETTING: The Nationwide Inpatient Sample and Kids' Inpatient
      Database were used to identify hospitalized pediatric surgical patients in the
      United States (aged 0-18 years) from 1988 to 2005. PATIENTS: After data from 1
      946 831 hospitalizations in children were linked to the Agency for Healthcare
      Research and Quality Pediatric Quality Indicator (PDI) software, 413 pediatric
      patients with foreign bodies left during a procedure (PDI 3) were identified. A
      1:3 matched case-control design was implemented with 413 cases and 1227 controls.
      Cases and controls were stratified into procedure categories based on diagnosis
      related group procedure codes. MAIN OUTCOME MEASURES: To examine the relationship
      between PDI 3 and procedure category, as well as the outcomes of in-hospital
      mortality, length of stay, and total hospital charges. RESULTS: Logistic
      regression analysis revealed a statistically significant higher odds of PDI 3 in
      the gynecology procedure category (odds ratio, 4.13; P = .01). Multivariable
      regression analysis revealed that patients with PDI 3 had an 8-day longer length
      of stay (95% confidence interval, 5.6-10.3 days; P < .001) and $35 681 higher
      total hospital charges (95% confidence interval, $22 358-$49 004; P < .001) but
      were not more likely to die (odds ratio, 1.07; P = .92). CONCLUSIONS: Among
      pediatric surgical admissions, a foreign body left during a procedure was
      observed to occur with highest likelihood during gynecologic operations. The
      occurrence of this adverse event was associated with longer length of stay and
      greater total hospital charges, but not with increased mortality.

PMID- 21079098
TI  - Surgeon subspecialty as a factor in improving long-term outcomes for gastric
      cancer: Twenty years of experience in Korea.
AB  - BACKGROUND: The results of gastric cancer treatment have improved during the past
      2 decades. In addition to early diagnosis, surgeon experience and subspecialty
      may influence long-term outcomes. This study analyzed data accumulated during the
      past 20 years regarding the impact of surgical subspecialty on gastric cancer
      prognosis. DESIGN: A 20-year, retrospective study. SETTING: Korea University Guro
      Hospital, Seoul. PATIENTS: A total of 2797 patients admitted between 1984 and
      2003 with surgically treated, pathologically confirmed, primary gastric
      adenocarcinoma. MAIN OUTCOME MEASURE: Long-term survival. RESULTS: The incidence
      of total gastrectomy and the number of retrieved lymph nodes increased during the
      study period. In curative cases, 5-year survival improved from 66.1% to 76.6%,
      and this survival gain was restricted to stages I, III, and IV. A Cox
      proportional hazards regression model showed that age, sex, tumor location, type
      of resection, stage, and the interaction between period of study and surgical
      subspecialty were independent prognostic factors. CONCLUSIONS: This large, long
      term cohort study demonstrates that the management of gastric cancer has been
      largely successful, with favorable trends in prognostic factors. Successful
      outcomes are realized more often by gastric surgical specialists. Efforts must be
      made to improve the treatment of patients with stage II gastric cancer because
      the improvements in long-term results have plateaued.

PMID- 21079099
TI  - Risk factors for invasive breast cancer when core needle biopsy shows ductal
      carcinoma in situ.
AB  - HYPOTHESIS: A core needle biopsy (CNB) diagnosis of ductal carcinoma in situ
      (DCIS) may be associated with a final diagnosis of invasive cancer. Preoperative
      radiologic, clinical, and pathological features may identify patients at high
      risk of diagnostic upstaging, who may be appropriate candidates for sentinel node
      biopsy at initial surgery. DESIGN: Review of prospectively collected database.
      SETTING: Tertiary teaching referral hospital and a population-based breast
      screening center. PATIENTS: Consecutive patients from January 1, 1994, to
      December 31, 2006, whose CNB findings showed DCIS or DCIS with microinvasion.
      MAIN OUTCOME MEASURES: Upstaging to invasive cancer. RESULTS: Eleven of 15 cases
      of DCIS with microinvasion (73.3%) and 65 of 375 cases of DCIS (17.3%) were
      upstaged to invasive cancer. Ten of 21 palpable lesions (47.6%) were found to
      have microinvasion. For impalpable DCIS, multivariate analysis showed that
      noncalcific mammographic features (mass, architectural distortion, or nonspecific
      density) (odds ratio [95% confidence interval], 2.00 [1.02-3.94]), mammographic
      size of 20 mm or greater (2.80 [1.46-5.38]), and prolonged screening interval of
      3 years or longer (4.41 [1.60-12.13]) were associated with upstaging. The DCIS
      grade on CNB was significant on univariate analysis (P = .04). The rate of
      upstaging increased with the number of significant factors present in a patient:
      8.3% in patients with no risk factors, 20.8% in those with 1 risk factor, 39.6%
      in those with 2 risk factors, and 57.1% in those with 3 risk factors.
      CONCLUSIONS: The risk of upstaging can be estimated by using preoperative
      features in patients with DCIS on CNB. We propose a management algorithm that
      includes sentinel node biopsy for patients with DCIS who have microinvasion on
      CNB, palpable DCIS, 2 or more predictive factors, and planned total mastectomy.

PMID- 21079100
TI  - Understanding the racial disparity in the receipt of endovascular abdominal
      aortic aneurysm repair.
AB  - HYPOTHESIS: Racial disparity exists in the management of abdominal aortic
      aneurysms (AAAs) using new health care technology. DESIGN: Retrospective cross
      sectional study. SETTING: Medicare database (January 1, 2001, to December 31,
      2006). PATIENTS: All patients who underwent open or endovascular AAA repair were
      identified (N = 160 785). MAIN OUTCOMES MEASURES: The relationship between race
      and the type of AAA repair (open vs endovascular), controlling for differences in
      patient factors and adjusting for the hospitals where patients received care.
      RESULTS: Accounting for differences in patient comorbidities and neighborhood
      socioeconomic status, black patients were 33% less likely than nonblack patients
      to undergo endovascular AAA repair (odds ratio, 0.67; 95% confidence interval,
      0.63-0.71). Black patients treated in hospitals with the highest proportions of
      black patients having AAA repair underwent endovascular AAA repair less often
      than black patients treated in hospitals with the lowest proportions of black
      patients having AAA repair (31.0% vs 39.6%, P < .05). Accounting for differences
      in the hospitals where they received care, black patients continued to have a
      significantly lower rate of endovascular AAA repair (odds ratio, 0.73; 95%
      confidence interval, 0.67-0.78). CONCLUSIONS: Despite controlling for differences
      in patient characteristics and the hospitals where they received care, black
      patients were still less likely to undergo endovascular AAA repair. Efforts aimed
      at improving this disparity will need to explore the causes of these treatment
      differences.

PMID- 21079101
TI  - Laparoscopic vs open hepatic resection for benign and malignant tumors: An
      updated meta-analysis.
AB  - OBJECTIVE: To compare laparoscopic hepatic resection (LHR) with open hepatic
      resection (OHR) for benign and malignant tumors. DATA SOURCES: MEDLINE, CENTRAL,
      and EMBASE databases were searched for relevant studies published between January
      1, 1998, and May 1, 2009. STUDY SELECTION: Studies clearly documenting a
      comparison of LHR with OHR for benign and malignant neoplasms were selected. DATA
      EXTRACTION: Operative and postoperative measures, resection margins,
      complications, and survival outcomes were evaluated. Weighted mean differences,
      relative risks, and hazard ratios (HRs) were calculated using a random-effects
      model. RESULTS: Twenty-six studies were included in the meta-analysis. The HR of
      death for malignant tumors was significantly lower in the LHR group compared with
      the OHR group (HR, 0.64; P = .04). The HR of recurrence for malignant tumors was
      not significantly different between the 2 groups (HR, 0.79; P = .37). The LHR
      group had a lower operative blood loss (weighted mean difference, -161 mL; P <
      .001) and relative risk of total postoperative complications (relative risk,
      0.40; P < .001). Duration of hospital stay, days of intravenous narcotic use, and
      days until oral intake were all significantly lower in the LHR group compared
      with the OHR group. Operative time between LHR and OHR was not significantly
      different. CONCLUSIONS: Laparoscopic hepatic resection for malignant tumors is
      associated with a long-term survival that is at least comparable, if not
      superior, to OHR with no difference in disease recurrence. The use of LHR for
      benign and malignant tumors is a safe alternative to OHR with potential operative
      and postoperative benefits.

PMID- 21079102
TI  - Women in surgery: a survey in Switzerland.
AB  - An increasing proportion of women work in medicine; however, only few choose
      surgical specialties. The objective of this study was to analyze the current
      situation of female surgeons and surgical residents in Switzerland concerning
      their personal and professional fulfillment. Of 318 female surgeons and surgical
      residents included in our study, 189 (59.4%) returned the anonymous
      questionnaire. Mentor-mentee relationships were mentioned by 110 (58.2%) of the
      189 respondents. On the basis of a 7-point Likert scale, these women responded
      that they were moderately satisfied with their professional (mean score [SD], 2.7
      [1.3]) and personal (mean score [SD], 3.0 [1.7]) lives. Of the 189 respondents,
      113 (59.8%) mentioned that they felt underappreciated. The most important ways
      suggested for increasing the attractiveness of a surgical career for women were a
      reduction in workload (49 respondents [25.9%]), more flexible working hours (38
      respondents [20.1%]), and better structured residency programs (23 respondents
      [12.2%]).

PMID- 21079103
TI  - Image of the month--quiz case. Transected right posterior hepatic duct.

PMID- 21079104
TI  - Image of the month--quiz case. Giant hepatic abscess.

PMID- 21079105
TI  - Forehead and scalp sensation after brow-lift: a comparison between open and
      endoscopic techniques.
AB  - OBJECTIVE: To compare postoperative forehead and scalp sensation for the "open"
      brow-lift (OBL) (coronal and trichophytic) with that of the endoscopic brow-lift
      (EBL). METHODS: A controlled outcome evaluation study was designed to objectively
      (mechanoceptive and thermoceptive) and subjectively (visual analog scale) test
      forehead and scalp sensation in a group of patients having undergone or scheduled
      to undergo either OBL or EBL in a single, private facial plastic surgery clinic.
      Prospectively enrolled participants were tested at defined intervals (A,
      preoperation; B,1-2 weeks after; C, 4-6 weeks after; D, 12-14 weeks after; and E,
      24-26 weeks after). To provide extended follow-up data (>=6 months), patients
      returning for scheduled follow-up examination who had already undergone either
      OBL or EBL were subjected to the same test battery. For statistical analysis of
      the extended follow-up data, the participants were divided into 2 groups (F, 6-18
      months; and G, >18 months). The null hypothesis was that there would be no
      measurable difference between the OBL and the EBL groups related to postoperative
      forehead and scalp sensation. RESULTS: Twenty-one individuals (EBL, n = 11; OBL,
      n = 10) were enrolled prospectively. All showed normal objective and subjective
      values preoperatively. While both groups objectively and subjectively
      demonstrated decreased sensation over follow-up, the OBL group showed
      statistically significant decrement in objective scalp sensitivity at times B, C,
      and D vs the EBL group. Subjectively, the OBL group felt less sensitive than the
      EBL group at times C and D. Those relationships disappeared at time E. Fifty
      eight individuals were retrospectively enrolled. At time F (EBL, n = 16; OBL, n =
      10), an objective and subjective difference was again observed with the OBL group
      demonstrating less scalp sensitivity vs the EBL group. At time G (EBL, n = 20;
      OBL, n = 12), this difference was no longer observed. CONCLUSIONS: We reject the
      null hypothesis and state that there is a measurable, statistically significant
      difference between the studied groups related to postoperative forehead and scalp
      sensation and that those observed differences are objective and subjective in
      nature as well as time dependent. However, almost no patients (57 of 58),
      irrespective of the technique used for their brow-lift, viewed their experienced
      forehead and/or scalp numbness to have been significant enough to deter them from
      undergoing the surgery again.

PMID- 21079106
TI  - Osseocartilaginous rib graft rhinoplasty: a stable, predictable technique for
      major dorsal reconstruction.
AB  - OBJECTIVE: To assess the long-term stability of osseocartilaginous dorsal onlay
      rib grafts used for augmentation rhinoplasty. METHODS: Patients who had rib
      grafts used for augmentation rhinoplasty from 2000 through 2009 were assessed for
      graft viability, graft mobility, graft warping, maintenance of dorsal projection,
      functional airway status, need for revision surgery, and donor site morbidity. A
      retrospective cohort study using telephone follow-up was conducted. RESULTS: A
      total of 58 rib graft rhinoplasties were performed in the 10-year review period,
      39 of which used dorsal onlay grafts. The mean duration of clinical follow-up was
      24 months, and the median duration of clinical follow-up was 16 months. Thirty
      three of 33 osseocartilaginous onlay grafts (100%) and 5 of 6 cartilaginous onlay
      grafts (83%) were viable, rigid, and had maintained dorsal projection at last
      follow-up. None of the grafts warped. Twenty-nine of 33 patients receiving
      osseocartilaginous onlay grafts (88%) and 5 of 6 patients receiving cartilaginous
      onlay grafts (83%) had persisting relief of their nasal obstruction. Twelve of
      the 39 patients (30%) had revision surgery, mostly performed for minor cosmetic
      revision. CONCLUSIONS: Osseocartilaginous onlay rib grafts provide an ideal
      scaffold for dorsal nasal augmentation and restoration of nasal airway in
      patients with collapse of the nasal framework due to a saddle deformity, history
      of trauma, or history of multiple septorhinoplasties. The graft has excellent
      viability, lacks potential for long-term warping, achieves bony fusion to the
      nasal bones, and allows surgical molding of the cartilaginous tip.

PMID- 21079107
TI  - Effects of corticosteroids on functional recovery and neuron survival after
      facial nerve injury in mice.
AB  - OBJECTIVES: To assess the effects of corticosteroid administration on functional
      recovery and cell survival in the facial motor nucleus (FMN) following crush
      injury in adult and juvenile mice and to evaluate the relationship between
      functional recovery and facial motoneuron survival. METHODS: A prospective
      blinded analysis of functional recovery and cell survival in the FMN after crush
      injury in juvenile and adult mice was carried out. All mice underwent a
      unilateral facial nerve crush injury and received 7 doses of daily injections.
      Adults received normal saline or low-dose or high-dose corticosteroid treatment.
      Juveniles received either normal saline or low-dose corticosteroid treatment.
      Whisker function was monitored to assess functional recovery. Stereologic
      analysis was performed to determine neuron and glial survival in the FMN
      following recovery. RESULTS: Following facial nerve injury, all adult mice
      recovered fully, while juvenile mice recovered slower and incompletely. This
      corresponded to a significantly greater neuron loss in the FMN of juveniles
      compared with adults. Corticosteroid treatment slowed functional recovery in
      adult mice. This corresponded with significantly greater neuron loss in the FMN
      in corticosteroid-treated mice. In juvenile mice, corticosteroid treatment showed
      a trend, which was significant at several time points, toward a more robust
      functional recovery compared with controls. CONCLUSIONS: Corticosteroid treatment
      slows functional recovery and impairs neuron survival following facial nerve
      crush injury in adult mice. The degree of motor neuron survival corresponds with
      functional status. In juvenile mice, crush injury results in overall poor
      functional recovery and profound cell loss in the FMN. With low-dose
      corticosteroid treatment, there is a significantly enhanced functional recovery
      after injury in these mice (P < .05).

PMID- 21079108
TI  - Surgeons' stress from surgery and night duty: a multi-institutional study.
AB  - OBJECTIVE: To examine the stress experienced by surgeons in response to surgery
      and night duty. DESIGN: Analyses were done by subjective questionnaires and an
      objective urine analysis. SETTING: One university hospital and 15
      community/public hospitals in Kitakyushu City, Japan. PARTICIPANTS: Sixty-six
      Japanese surgeons. MAIN OUTCOME MEASURES: Scores on the NASA Task Load Index and
      Stress Arousal Checklist and urine biopyrin levels. RESULTS: The Task Load Index
      score significantly increased in association with the duration of surgery and the
      amount of surgical blood loss. Urine biopyrin levels significantly increased with
      the duration of surgery. Night duty significantly decreased sleep time and
      significantly increased urine biopyrin levels. Stress Arousal Checklist Arousal
      Scale scores significantly decreased the morning after night duty and the evening
      after the end of the following day shift. CONCLUSION: Surgery was associated with
      stress on surgeons and night duty influenced the arousal of the surgeons during
      the day shift following night duty.

PMID- 21079109
TI  - Comparative benefits of laparoscopic vs open hepatic resection: a critical
      appraisal.
AB  - OBJECTIVES: To perform a literature review examining the comparative benefits of
      laparoscopic vs open hepatic resection and to define the benefits and outcomes of
      laparoscopic liver resection in our own series of 314 patients. DATA SOURCES:
      Cited English-language publications from PubMed. In addition, between 2001 to
      2010, hepatic resections were performed in our institution in 1294 patients, of
      whom 314 patients (24.3%) underwent laparoscopic liver resection for benign or
      malignant liver lesions. STUDY SELECTION: Search phrases were "laparoscopic liver
      resection," "open liver resection," "versus," "compared with," and "advantages."
      DATA EXTRACTION: Thirty-one studies were reviewed that directly compared
      laparoscopic with open hepatic resection in 2473 patients. DATA SYNTHESIS: In
      case-cohort matched studies, and our institutional series, laparoscopic liver
      resection was associated with less blood loss, quicker resumption of oral diet,
      less pain medication requirement, and shorter length of stay, with no difference
      in complication rates. In those patients undergoing laparoscopic hepatic
      resection for malignancy, there was no difference in 3- or 5-year overall
      survival when compared with well-matched open hepatic resection cases.
      Financially, the total hospital costs of laparoscopic liver resection were either
      offset or improved because of a shorter length of stay. CONCLUSIONS: Based on
      review of the literature and our institutional series, minimally invasive hepatic
      resection for benign and malignant liver lesions is safe and feasible with
      significant benefits for patients consisting of less blood loss, less narcotic
      requirements, and shorter length of hospital stay. There are no economic
      disadvantages to the laparoscopic approach, and case-cohort matched studies show
      no difference in oncologic outcomes between the laparoscopic and open groups.

PMID- 21079110
TI  - Evaluating an evidence-based bundle for preventing surgical site infection: a
      randomized trial.
AB  - OBJECTIVE: To determine if an evidence-based practice bundle would result in a
      significantly lower rate of surgical site infections (SSIs) when compared with
      standard practice. DESIGN: Single-institution, randomized controlled trial with
      blinded assessment of main outcome. The trial opened in April 2007 and was closed
      in January 2010. SETTING: Veterans Administration teaching hospital. PATIENTS:
      Patients who required elective transabdominal colorectal surgery were eligible. A
      total of 241 subjects were approached, 211 subjects were randomly allocated to 1
      of 2 interventions, and 197 were included in an intention-to-treat analysis.
      INTERVENTIONS: Subjects received either a combination of 5 evidenced-based
      practices (extended arm) or were treated according to our current practice
      (standard arm). The interventions in the extended arm included (1) omission of
      mechanical bowel preparation; (2) preoperative and intraoperative warming; (3)
      supplemental oxygen during and immediately after surgery; (4) intraoperative
      intravenous fluid restriction; and (5) use of a surgical wound protector. MAIN
      OUTCOME MEASURE: Overall SSI rate at 30 days assessed by blinded infection
      control coordinators using standardized definitions. RESULTS: The overall rate of
      SSI was 45% in the extended arm of the study and 24% in the standard arm (P =
      .003). Most of the increased number of infections in the extended arm were
      superficial incisional SSIs (36% extended arm vs 19% standard arm; P = .004).
      Multivariate analysis suggested that allocation to the extended arm of the trial
      conferred a 2.49-fold risk (95% confidence interval, 1.36-4.56; P = .003)
      independent of other factors traditionally associated with SSI. CONCLUSIONS: An
      evidence-based intervention bundle did not reduce SSIs. The bundling of
      interventions, even when the constituent interventions have been individually
      tested, does not have a predictable effect on outcome. Formal testing of bundled
      approaches should occur prior to implementation.

PMID- 21079112
TI  - In praise of rhinoplasty.

PMID- 21079111
TI  - Robotic-assisted major pancreatic resection and reconstruction.
AB  - HYPOTHESIS: Robotic-assisted pancreatic resection and reconstruction are safe and
      can reproduce perioperative results seen in open surgery. DESIGN: Single
      institution retrospective review. SETTING: Tertiary care center. PATIENTS:
      Patients undergoing completed robotic-assisted pancreatic resection and
      reconstruction at the University of Pittsburgh Medical Center, Pittsburgh,
      Pennsylvania, between October 3, 2008, and February 26, 2010. MAIN OUTCOME
      MEASURES: Primary pathology, operative time, operative blood loss, perioperative
      blood transfusions, pancreatic fistula, 90-day morbidity and mortality, and
      readmission rate. RESULTS: Thirty patients with a median age of 70 years (range,
      32-85 years) underwent completed robotic-assisted pancreatic resection and
      reconstruction. Procedures were robotic-assisted non-pylorus-preserving
      pancreaticoduodenectomy (n = 24), robotic-assisted central pancreatectomy (n =
      4), and the robotic-assisted Frey procedure (n = 2). The median operative time
      was 512 minutes (range, 327-848 minutes). The median blood loss was 320 mL
      (range, 50-1000 mL), with a median length of hospital stay of 9 days (range, 4-87
      days). The final diagnoses included periampullary adenocarcinoma (n = 7),
      pancreatic ductal adenocarcinoma (n = 6), pancreatic neuroendocrine tumor (n =
      5), intraductal papillary mucinous neoplasm (n = 4), mucinous cystic neoplasm (n
      = 3), serous cystic adenoma (n = 2), chronic pancreatitis (n = 2), and solid
      pseudopapillary neoplasm (n = 1). There was 1 postoperative death. The overall
      pancreatic fistula rate was 27% (n = 8). The clinically significant pancreatic
      fistula rate (International Study Group on Pancreatic Fistula grades B and C) was
      10% (n = 3). Clavien grade III and IV complications occurred in 7 patients (23%),
      while Clavien grade I and II complications occurred in 8 patients (27%).
      CONCLUSIONS: Robotic-assisted complex pancreatic surgery can be performed safely
      in a high-volume pancreatic tertiary care center with perioperative outcomes
      comparable to those of open surgery. Advances in robotic technology and
      increasing experience may improve long operative times.

PMID- 21079114
TI  - Cephalic positioning of the lateral crura: implications for nasal tip-plasty.
AB  - OBJECTIVE: To apply a mathematical model to determine the relative effectiveness
      of various tip-plasty maneuvers while the lateral crura are in cephalic position
      compared with orthotopic position. METHODS: A Matlab (MathWorks, Natick,
      Massachusetts) computer program, called the Tip-Plasty Simulator, was developed
      to model the medial and lateral crura of the tripod concept in order to estimate
      the change in projection, rotation, and nasal length yielded by changes in crural
      length. The following rhinoplasty techniques were modeled in the software
      program: columellar strut graft/tongue-in-groove, lateral crural steal, lateral
      crural overlay, medial/intermediate crural overlay, hinge release with alar strut
      graft, and lateral crural repositioning. RESULTS: Using the Tip-Plasty Simulator,
      the directionality of the change in projection, rotation, and nasal length
      produced by the various tip-plasty maneuvers, as shown by our mathematical model,
      is largely the same as that expected and observed clinically. Notably,
      cephalically positioned lateral crura affected the results of the rhinoplasty
      maneuvers studied. CONCLUSIONS: By demonstrating a difference in the magnitude of
      change resulting from various rhinoplasty maneuvers, the results of this study
      enhance the ability of the rhinoplasty surgeon to predict the effects of various
      tip-plasty maneuvers, given the variable range in alar cartilage orientation that
      he or she is likely to encounter.

PMID- 21079113
TI  - Glutathione-S-transferase polymorphisms and complications of microvascular head
      and neck reconstruction.
AB  - BACKGROUND: Glutathione-S-transferase (GST) enzymes play a role in scavenging
      endogenous oxidants. Altered enzyme activity results from inherited
      polymorphisms, which results in increased oxidative stress. This study explores
      the role of GST polymorphisms as modifiers of surgical complications in patients
      undergoing head and neck microvascular reconstruction. METHODS: Patients newly
      diagnosed as having head and neck cancer and undergoing microvascular
      reconstruction were selected. Polymerase chain reaction was used to determine GST
      genotypes. Demographic factors, treatment, and postoperative complications were
      reviewed. Multivariate logistic regression analysis was used to estimate the risk
      of surgical complications associated with variant genotypes. RESULTS: A total of
      107 patients were evaluated. Surgical and medical complication rates were 44.9%
      and 25.2%, respectively. The variant Val allele at the GSTP1 105 codon was
      associated with a significantly increased risk of surgical complications (P =
      .046; adjusted relative risk, 1.7; 95% confidence interval, 1.1-2.6). There was
      no significant association between the other GST variant genotypes and surgical
      complications. No association was noted between variant GST genotypes and the
      risk of medical complications. CONCLUSION: GSTP1 codon 105 polymorphism may be a
      marker for risk of wound complications in head and neck microvascular
      reconstruction.

PMID- 21079115
TI  - Engineering analysis of an unreported complication of septoplasty.
AB  - OBJECTIVES: To describe a cause of recurrent nasal obstructive symptoms after
      septoplasties including the creation of a sizable submucous window and to suggest
      treatments for this complication. METHODS: Case report of a woman presenting with
      side-changing nasal dyspnea approximately 1 year after undergoing septoplasty and
      engineering analysis of nasal cavity airflow. We created a computer model of the
      airway, analyzed varying sizes of surgical defects, and optimized the geometry of
      the submucous window. RESULTS: An optimum area of resection to maximize the area
      of cartilage and/or bone resected and to minimize deflection of the septal area
      of iatrogenic litheness is a rectangular shape approximately 44 mm long by 12 mm
      high in our model. CONCLUSIONS: A large submucous window can result in
      obstruction of nasal airflow after septoplasty owing to displacement of this
      compliant area with respiration under the forces described in the Bernoulli
      theorem. Treatment may include turbinate reduction and/or septal reconstruction.

PMID- 21079116
TI  - Accuracy of preoperative computer imaging in rhinoplasty.
AB  - OBJECTIVE: To quantitatively measure the accuracy of preoperative computer
      imaging (PCI) as a reflection of postoperative rhinoplasty results. METHODS:
      Thirty-eight patients underwent primary and revision rhinoplasty. Six-month
      postoperative photographs and "morphed" PCI images were graded on a 5-point
      Likert scale by 2 panels of judges, one composed of surgeons and the other of
      nonsurgeons. Twelve parameters were assessed. Results were stratified based on
      primary vs revision rhinoplasty and degree of difficulty of the rhinoplasties.
      Patient surveys were conducted to determine correlation between satisfaction and
      PCI accuracy. RESULTS: Mean overall accuracy was 2.98 by the expert panel,
      indicating moderate PCI accuracy. Supratip height was the lowest-rated parameter,
      while measurements of the upper third were most accurate. The accuracy in primary
      rhinoplasty was comparable to that found in revision surgery, although tougher
      cases were rated lower in overall accuracy and projection score. Satisfied
      patients had significantly higher PCI accuracy scores, and most patients found
      the PCI extremely useful. CONCLUSIONS: Preoperative computer imaging is a useful
      exercise, valued by patients during the rhinoplasty consultation. Accuracy is
      moderate in both primary and revision cases, although supratip edema is a
      limiting factor at the 6-month mark.

PMID- 21079117
TI  - Repair of orbital floor fractures using bioresorbable poly-L/DL-lactide plates.
AB  - OBJECTIVE: To assess the long-term clinical and radiologic findings after
      insertion of a bioresorbable polylactide plates P(L/DL)LA 70/30 implant (PolyMax)
      in the repair of orbital floor and wall defects, with special focus on stability
      and clinical signs of foreign-body reaction. METHODS: Forty-six patients who had
      orbital blowout fractures with at least 1.5-cm(2) bone defects in 1 or 2 walls
      were included in this retrospective study. Each defect was reconstructed within 2
      weeks of injury using a triangle form plate of polylactide. Computed tomography
      (CT) was performed before the operation and 1 year postoperatively. In 17
      patients, additional CT was performed within 2 to 3 years postoperatively.
      Clinical assessments were performed preoperatively and at 3-, 6-, and 12-month
      intervals postoperatively. RESULTS: None of the patients showed clinical foreign
      body reactions. There was no evidence of infection. Diplopia was seen in 6
      patients 3 months postoperatively but normalized in 5 patients at 6 months. Mild
      enophthalmos was seen in 2 patients postoperatively at 1 year. No sagging of the
      reconstructed area was found on CT. CONCLUSIONS: The P(L/DL)LA 70/30 implant is a
      well-tolerated, reliable material in orbital repair of relatively large defects.
      The bioresorbable plate leaves a stable bridge of healed bone or soft tissue
      after complete degradation.

PMID- 21079119
TI  - Hybrid rhinoplasty: the 21st century approach to remodeling the nose.

PMID- 21079118
TI  - Stabilization of costal cartilage graft warping using infrared laser irradiation
      in a porcine model.
AB  - OBJECTIVE: To develop a method to rapidly stabilize the shape change process in
      peripheral slices of costal cartilage by using infrared laser irradiation in a
      porcine model. METHODS: Forty peripheral porcine costal cartilage specimens (40 *
      10 * 2 mm) were harvested. Thirty of these specimens were immediately irradiated
      with an Nd:YAG laser (lambda = 1.32 MUm; spot size, 2-mm diameter) using 1 of 3
      exposure treatments: 6 W, 2 seconds, and 4 spots; 8 W, 3 seconds, and 4 spots; or
      6 W, 2 seconds, and 8 spots. Ten control specimens were only immersed in 0.9%
      saline solution. Angle of curvature was measured from photographs taken at 0
      minutes, immediately after irradiation, and at 30 minutes, 1 hour, 5 hours, and
      24 hours. Infrared imaging was used to measure surface temperatures during
      irradiation. Cell viability after irradiation was determined using a live/dead
      assay in conjunction with fluorescent confocal microscopy. RESULTS: Compared with
      the untreated controls, the irradiated grafts underwent accelerated shape change
      within the first 30 minutes to reach a stable geometry. Thereafter, irradiated
      grafts underwent little or no shape change, whereas the control group exhibited
      significant change in curvature from 30 minutes to 24 hours (P < .001). The
      average peak irradiated spot temperatures ranged from 76 degrees C to 82 degrees
      C. Cell viability measurements at the laser spot sites demonstrated a
      hemispherically shaped region of dead cells with a depth of 0.8 to 1.2 mm and a
      surface diameter of 1.9 to 2.7 mm. CONCLUSIONS: Laser irradiation of peripheral
      costal cartilage slices provides an effective method for rapidly stabilizing
      acute shape change by accelerating the warping process. The temperature
      elevations necessary to achieve this are spatially limited and well within the
      limits of tolerable tissue injury.

PMID- 21079120
TI  - Barrel roll technique for the correction of long and concave lateral crura.
AB  - OBJECTIVE: To describe the barrel roll technique that is capable of concurrently
      correcting 2 associated deformities--overprojection and ptosis of the nasal tip.
      METHODS: Thirty-two patients with concavity of the upper section of 1 or both
      lateral crura combined with a droopy tip were treated from January 1, 2005,
      through December 31, 2007. In all cases, the barrel roll technique was used,
      which involves rotating the lateral crus by 180 degrees  on its major axis so
      that the concavity is transformed into convexity, and carrying out lateral crural
      overlay to correct the overprojection concurrently. RESULTS: All the patients
      displayed functional and aesthetic improvement by correcting the droopy tip and
      concavity of the lateral crura. Revision was necessary in 1 case of monolateral
      concavity. The comparison of preoperative and postoperative rhinomanometric data
      showed significant improvement of nasal airway resistance. CONCLUSIONS: A
      combination of the overlay technique and rotation of a portion of the lateral
      crus on its axis is capable of concurrently correcting serious functional
      problems and aesthetic defects of the nasal tip. The open approach is essential
      for perfect positioning of the mobilized cartilaginous segments and ensuring
      stable results over time.

PMID- 21079121
TI  - Oblique septal crossbar graft for anterior septal angle reconstruction.
AB  - Nasal septal deformity is a central feature of the crooked nose, contributing to
      functional and aesthetic problems. Straightening of the septum often requires
      resection, scoring, or incision of the septum--maneuvers that inevitably weaken
      the cartilaginous dorsal and caudal L-shaped struts, which together are known as
      the L-strut. Compromise of this L-strut predisposes to septal buckling, recurrent
      deviation, and saddle nose deformity. We describe our experience with the oblique
      septal crossbar, a structural graft that allows biomechanically sound anterior
      septal angle reconstruction during septorhinoplasty. The technique improves
      dorsal septal support and facilitates correction of the crooked nose. The open
      septorhinoplasty approach and swinging door maneuver are followed by placement of
      a diagonally oriented crossbar graft, obtained from cartilage or the
      perpendicular plate. The approach allows consistent midline correction and
      buttressing of the nasal dorsum, with no complications to date.

PMID- 21079122
TI  - Lateral crural setback with cephalic turn-in flap: a method to treat the drooping
      nose.
AB  - Herein, I describe lateral crural setback with cephalic turn-in flap as a new
      technique for management of the drooping nose. I report a technique for
      reinforcement of the alar cartilage after partial removal of its caudal portion
      used in 23 patients during open rhinoplasty. An objective assessment, which
      included measurement of nasal tip rotation and projection, was applied
      preoperatively and postoperatively. The average follow-up period was 11 months.
      Satisfactory results were achieved that resulted in an increase in the degree of
      nasal tip rotation. The mean increase of the nasolabial angle was 12 degrees .
      This technique allows increasing the nasal tip rotation in an incremental fashion
      with preservation of nasal valve function and the strength and stability of the
      tip complex.

PMID- 21079123
TI  - Differences in brain structure related to laterality of cleft lip.

PMID- 21079125
TI  - Multidose of restylane for facial augmentation.

PMID- 21079126
TI  - Facial plastic surgical outcomes and clinical depression.

PMID- 21079127
TI  - A classification for degree of crushed cartilage.

PMID- 21079131
TI  - Addition of octreotide functional imaging to cross-sectional computed tomography
      or magnetic resonance imaging for the detection of neuroendocrine tumors: added
      value or an anachronism?

PMID- 21079132
TI  - The swinging pendulum of the anemia of cancer: erythropoietin trumps hepcidin.

PMID- 21079134
TI  - European Organisation for Research and Treatment of Cancer recommendations for
      planning and delivery of high-dose, high-precision radiotherapy for lung cancer.
AB  - PURPOSE: To derive recommendations for routine practice and clinical trials for
      techniques used in high-dose, high-precision thoracic radiotherapy for lung
      cancer. METHODS: A literature search was performed to identify published articles
      considered both clinically relevant and practical to use. Recommendations were
      categorized under the following headings: patient selection, patient positioning
      and immobilization, tumor motion, computed tomography and [18F]fluorodeoxyglucose
      positron emission technology scanning, generating target volumes, radiotherapy
      treatment planning, treatment delivery, and scoring of response and toxicity. The
      American College of Chest Physicians grading of recommendations was used.
      RESULTS: Recommendations were identified for each of the recommendation
      categories. Although most of the recommended techniques have not been evaluated
      in multicenter clinical trials, their use in high-precision thoracic radiotherapy
      and stereotactic body radiotherapy (SBRT) appears to be justified on the basis of
      available evidence. CONCLUSION: Recommendations to facilitate the clinical
      implementation of high-precision conformal radiotherapy and SBRT for lung tumors
      were identified from the literature. Some techniques that are considered
      investigational at present were also highlighted.

PMID- 21079133
TI  - Prognostic significance of expression of a single microRNA, miR-181a, in
      cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B
      study.
AB  - PURPOSE: To evaluate the prognostic significance of expression levels of a single
      microRNA, miR-181a, in the context of established molecular markers in
      cytogenetically normal acute myeloid leukemia (CN-AML), and to gain insight into
      the leukemogenic role of miR-181a. PATIENTS AND METHODS: miR-181a expression was
      measured in pretreatment marrow using Ohio State University Comprehensive Cancer
      Center version 3.0 arrays in 187 younger (<60 years) adults with CN-AML. Presence
      of other molecular prognosticators was assessed centrally. A gene-expression
      profile associated with miR-181a expression was derived using microarrays and
      evaluated by Gene-Ontology analysis. RESULTS: Higher miR-181a expression
      associated with a higher complete remission (CR) rate (P=.04), longer overall
      survival (OS; P=.01) and a trend for longer disease-free survival (DFS; P=.09).
      The impact of miR-181a was most striking in poor molecular risk patients with
      FLT3-internal tandem duplication (FLT3-ITD) and/or NPM1 wild-type, where higher
      miR-181a expression associated with a higher CR rate (P=.009), and longer DFS
      (P<.001) and OS (P<.001). In multivariable analyses, higher miR-181a expression
      was significantly associated with better outcome, both in the whole patient
      cohort and in patients with FLT3-ITD and/or NPM1 wild-type. These results were
      also validated in an independent set of older (>=60 years) patients with CN-AML.
      A miR-181a-associated gene-expression profile was characterized by enrichment of
      genes usually involved in innate immunity. CONCLUSION: To our knowledge, we
      provide the first evidence that the expression of a single microRNA, miR-181a, is
      associated with clinical outcome of patients with CN-AML and may refine their
      molecular risk classification. Targeted treatments that increase endogenous
      levels of miR-181a might represent novel therapeutic strategies.

PMID- 21079135
TI  - Promise and challenge of RNA interference-based therapy for cancer.
AB  - Cancer therapeutics still fall far short of our goals for treating patients with
      locally advanced or metastatic disease. Until recently, almost all cancer drugs
      were crude cytotoxic agents that discriminate poorly between cancer cells and
      normally dividing cells. The development of targeted biologics that recognize
      tumor cell surface antigens and of specific inhibitors of pathways dysregulated
      in cancer cells or normal cellular pathways on which a cancer cell differentially
      depends has provided hope for converting our increasing understanding of cellular
      transformation into intelligently designed anticancer therapeutics. However, new
      drug development is painfully slow, and the pipeline of new therapeutics is thin.
      The discovery of RNA interference (RNAi), a ubiquitous cellular pathway of gene
      regulation that is dysregulated in cancer cells, provides an exciting opportunity
      for relatively rapid and revolutionary approaches to cancer drug design. Small
      RNAs that harness the RNAi machinery may become the next new class of drugs for
      treating a variety of diseases. Although it has only been 9 years since RNAi was
      shown to work in mammalian cells, about a dozen phase I to III clinical studies
      have already been initiated, including four for cancer. So far there has been no
      unexpected toxicity and suggestions of benefit in one phase II study. However,
      the obstacles for RNAi-based cancer therapeutics are substantial. This article
      will discuss how the endogenous RNAi machinery might be harnessed for cancer
      therapeutics, why academic researchers and biotech and pharmaceutical companies
      are so excited, and what the obstacles are and how they might be overcome.

PMID- 21079136
TI  - Immunotherapy for ovarian cancer: what's next?
AB  - In the past decade, we have witnessed important gains in the treatment of ovarian
      cancer; however, additional advances are required to reduce mortality. With
      compelling evidence that ovarian cancers are immunogenic tumors, immunotherapy
      should be further pursued and optimized. The dramatic advances in laboratory and
      clinical procedures in cellular immunotherapy, along with the development of
      powerful immunomodulatory antibodies, create new opportunities in ovarian cancer
      therapeutics. Herein, we review current progress and future prospects in vaccine
      and adoptive T-cell therapy development as well as immunomodulatory therapy tools
      available for immediate clinical testing.

PMID- 21079137
TI  - BRCA1-associated breast cancers present differently from BRCA2-associated and
      familial cases: long-term follow-up of the Dutch MRISC Screening Study.
AB  - PURPOSE: The Dutch MRI Screening Study on early detection of hereditary breast
      cancer started in 1999. We evaluated the long-term results including separate
      analyses of BRCA1 and BRCA2 mutation carriers and first results on survival.
      PATIENTS AND METHODS: Women with higher than 15% cumulative lifetime risk (CLTR)
      of breast cancer were screened with biannual clinical breast examination and
      annual mammography and magnetic resonance imaging (MRI). Participants were
      divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two
      familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR).
      RESULTS: Our update contains 2,157 eligible women including 599 mutation carriers
      (median follow-up of 4.9 years from entry) with 97 primary breast cancers
      detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was
      superior to that of mammography for invasive cancer (77.4% v 35.5%; P<.00005),
      but not for ductal carcinoma in situ. Results in the BRCA1 group were worse
      compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for
      mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis<=1
      cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%)
      and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger
      than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall
      survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast
      cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%),
      respectively, and 100% in the familial groups (n=43). CONCLUSION: Screening
      results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was
      high in all risk groups.

PMID- 21079138
TI  - Population-based risks of CNS tumors in survivors of childhood cancer: the
      British Childhood Cancer Survivor Study.
AB  - PURPOSE: CNS tumors are the most common second primary neoplasm (SPN) observed
      after childhood cancer in Britain, but the relationship of risk to doses of
      previous radiotherapy and chemotherapy is uncertain. METHODS: The British
      Childhood Cancer Survivor Study is a national, population-based, cohort study of
      17,980 individuals surviving at least 5 years after diagnosis of childhood
      cancer. Linkage to national, population-based cancer registries identified 247
      SPNs of the CNS. Cohort and nested case-control studies were undertaken. RESULTS:
      There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in
      the analysis. The risk of meningioma increased strongly, linearly, and
      independently with each of dose of radiation to meningeal tissue and dose of
      intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99,
      10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and>=40 Gy had risks that were two
      fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks
      experienced by those whose meningeal tissue was unexposed. The risk of meningioma
      among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of
      intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the
      risk experienced by those unexposed. The standardized incidence ratio for gliomas
      was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal
      tumors increased linearly with dose of radiation, and those who had CNS tissue
      exposed to at least 40 Gy experienced a risk four-fold that experienced by those
      who had CNS tissue unexposed. CONCLUSION: The largest-ever study, to our
      knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk
      of meningioma increases rapidly with increased dose of radiation to meningeal
      tissue and with increased dose of intrathecal methotrexate.

PMID- 21079139
TI  - Contractile reserve as a marker of preclinical cardiotoxicity.

PMID- 21079140
TI  - Routine preventive care and cancer surveillance in long-term survivors of
      colorectal cancer: results from National Surgical Adjuvant Breast and Bowel
      Project Protocol LTS-01.
AB  - PURPOSE: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol LTS
      01 examines routine preventive care and cancer surveillance in long-term
      colorectal cancer (CRC) survivors previously treated in NSABP adjuvant trials.
      PATIENTS AND METHODS: Long-term CRC survivors (>=5 years) from five completed
      NSABP trials (Protocols C-05, C-06, C-07, R-02, and R-03) at 60 study sites were
      recruited and surveyed using preventive health care items from the National
      Health Interview Survey (NHIS). A 3:1 comparison cohort case-matched by age, sex,
      race, and education was created from the 2005 NHIS. Contingency tables and
      multivariate models were used to compare cohorts and determine predictors of
      preventive care and cancer surveillance. RESULTS: A total of 708 patients in
      protocol LTS-01 (681 patients with colon cancer, 27 patients with rectal cancer)
      completed the interview: 57.1% male, mean age 66.2 years (standard
      deviation=10.6), median survival 8 years. Patients in the LTS-01 protocol were
      more likely to have a usual source of health care (97.7% v 93.8%, P<.0001), have
      received a flu shot in the past 12 months (67.5% v 44.3%, P<.0001), and have
      undergone cancer screening by Pap smear (67.3% v 54.8%, P<.0001), mammogram
      (80.4% v 70.7%, P<.0001), and prostate-specific antigen test (84.5% v 74.5%,
      P<.0001) than patients in the NHIS cohort. For CRC surveillance, 96.5% of
      patients in protocol LTS-01 had a colonoscopy, 88.2% had a carcinoembryonic
      antigen test, and 66.4% had a computed tomography scan in the previous 5 years.
      Health insurance was the best predictor of cancer screening for all three methods
      (odds ratio=2.6 to 4.5). No factor was uniformly associated with CRC
      surveillance. CONCLUSION: This select population of long-term CRC survivors who
      participated in clinical trials achieved better routine preventive care and
      cancer screening than the general population and high rates of cancer
      surveillance.

PMID- 21079142
TI  - A hallmark moment.

PMID- 21079141
TI  - Induction docetaxel, cisplatin, and cetuximab followed by concurrent
      radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with
      locally advanced head and neck cancer.
AB  - PURPOSE: We incorporated cetuximab, a chimeric monoclonal antibody against the
      epidermal growth factor receptor (EGFR), into the induction therapy and
      subsequent chemoradiotherapy of head and neck cancer (HNC). PATIENTS AND METHODS:
      Patients with locally advanced HNC, including squamous and undifferentiated
      histologies, were treated with docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day
      1, and cetuximab 250 mg/m2 days 1, 8, and 15 (after an initial loading dose of
      400 mg/m2), termed TPE, repeated every 21 days for three cycles, followed by
      radiotherapy with concurrent cisplatin 30 mg/m2 and cetuximab weekly (XPE), and
      maintenance cetuximab for 6 months. Quality of life (QOL) was assessed using
      Functional Assessment of Cancer Therapy-Head and Neck. In situ hybridization
      (ISH) for human papillomavirus (HPV), immunohistochemistry for p16, and
      fluorescence ISH for EGFR gene copy number were performed on tissue microarrays.
      RESULTS: Of 39 enrolled patients, 36 had stage IV disease and 23 an oropharyngeal
      primary. Acute toxicities during TPE included neutropenic fever (10%) and during
      XPE, grade 3 or 4 oral mucositis (54%) and hypomagnesemia (39%). With a median
      follow-up of 36 months, 3-year progression-free survival and overall survival
      were 70% and 74%, respectively. Eight patients progressed in locoregional sites,
      three in distant, and one in both. HPV positivity was not associated with
      treatment efficacy. No progression-free patient remained G-tube dependent. The
      H&N subscale QOL scores showed a significant decrement at 3 months after XPE,
      which normalized at 1 year. CONCLUSION: This cetuximab-containing regimen
      resulted in excellent long-term survival and safety, and warrants further
      evaluation in both HPV-positive and -negative HNC.

PMID- 21079143
TI  - Study inclusion criteria and presentation of results in a meta-analysis of
      granulocyte colony-stimulating factor for prevention of febrile neutropenia.

PMID- 21079144
TI  - Ascertainment of patients with myelodysplastic syndromes.

PMID- 21079145
TI  - The evolving role of histology in the management of advanced non-small-cell lung
      cancer.
AB  - Until recently, non-small-cell lung cancer (NSCLC) was treated as a single
      disease despite recognition of its histologic and molecular heterogeneity. Recent
      clinical trials, however, demonstrate that histology is an important factor for
      individualizing treatment, based on either safety or efficacy outcomes. For
      example, the labeling of the licensed agents bevacizumab and pemetrexed is
      restricted to patients with nonsquamous cell NSCLC. For bevacizumab, this
      restriction is due to an apparent association between squamous cell histology and
      severe pulmonary hemorrhage, whereas for pemetrexed, superior treatment effects
      have been observed in patients with nonsquamous cell histology. Given fewer
      agents are both active and tolerable in patients with squamous cell carcinoma
      compared with adenocarcinoma, and the nature of this particular phenotype of
      NSCLC, new drugs are needed for this histology. In this new histology-based
      treatment era, questions persist. Can pathology accurately distinguish the
      histologic subtypes of NSCLC? Can we use cytologic diagnosis? In the future, will
      molecular profiling of tumors trump histologic analysis? Herein we describe how
      therapy for NSCLC is evolving on the basis of a better understanding of molecular
      mechanisms underlying NSCLC histologic heterogeneity and tumorigenesis.

PMID- 21079146
TI  - Plasma transforming growth factor alpha and amphiregulin protein levels in NCIC
      Clinical Trials Group BR.21.
AB  - PURPOSE: To evaluate the prognostic and predictive significance of plasma levels
      of the epidermal growth factor receptor (EGFR) ligands, transforming growth
      factor alpha (TGF-alpha) and amphiregulin, in patients with non-small-cell lung
      cancer (NSCLC) enrolled in NCIC Clinical Trials Group BR.21 comparing erlotinib
      with placebo. PATIENTS AND METHODS: TGF-alpha and amphiregulin were assessed
      retrospectively by enzyme-linked immunosorbent assay from available prospectively
      collected baseline plasma samples in 565 of 731 BR.21 patients. Cutoff points
      were determined for both amphiregulin (low, <10 pg/mL; high, >=10 pg/mL) and TGF
      alpha (low, <=12 pg/mL; high, >12 pg/mL) using a graphical method. Cox regression
      models were used to correlate biomarker data and baseline characteristics with
      outcomes including overall (OS) and progression-free survival (PFS). RESULTS:
      High TGF-alpha and amphiregulin were associated with poorer performance status
      (P=.06 and P<.0001, respectively) and no prior platinum therapy (P=.06 and P=.02,
      respectively). High amphiregulin was also associated with anemia (P=.001),
      increased lactate dehydrogenase (P=.03), ever-smokers (P=.04), and non-Asian
      ethnicity (P=.001). Patients on the placebo arm with high amphiregulin had poorer
      OS than patients with low amphiregulin (hazard ratio [HR]=1.88; 95% CI, 1.34 to
      2.64; P=.0002), which remained significant in multivariate analysis. Amphiregulin
      levels did not predict for benefit from erlotinib (interaction P=.87).
      Conversely, TGF-alpha levels did not have prognostic significance, but high TGF
      alpha predicted lack of benefit from erlotinib compared with low TGF-alpha (TGF
      alpha low, OS HR=0.66; 95% CI, 0.54 to 0.81; P<.0001; high, OS HR=1.32; 95% CI,
      0.73 to 2.39; P=.36; interaction P=.04). CONCLUSION: High baseline amphiregulin
      is a poor prognostic factor, whereas high baseline TGF-alpha predicts for lack of
      benefit from erlotinib in advanced NSCLC.

PMID- 21079147
TI  - Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus
      carboplatin in chemotherapy-naive patients with advanced non-small-cell lung
      cancer: results of a west Japan oncology group study.
AB  - PURPOSE: The primary goal of this open-label, multicenter, randomized phase III
      trial was to determine whether treatment with carboplatin plus the oral
      fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus
      paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients
      with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total
      of 564 patients were randomly assigned to receive either carboplatin (area under
      the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or
      carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every
      21 days. RESULTS: At the planned interim analysis, with a total of 268 death
      events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a
      positive result and noninferiority of carboplatin and S-1 compared with
      carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI,
      0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and
      13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of
      57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4,
      febrile neutropenia, alopecia, and neuropathy were more frequent in the
      carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and
      diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1
      arm had significantly more dose delays than the carboplatin and paclitaxel arm.
      CONCLUSION: Oral S-1 with carboplatin was noninferior in terms of OS compared
      with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a
      valid treatment option.

PMID- 21079148
TI  - Fluorouracil induces myocardial ischemia with increases of plasma brain
      natriuretic peptide and lactic acid but without dysfunction of left ventricle.
AB  - PURPOSE: Fluorouracil (FU) is a cornerstone of colorectal cancer treatment;
      however, it has clinical and subclinical influence on the heart. This study aimed
      to clarify the pathophysiology, risk factors, and long-term effects of FU
      cardiotoxicity. PATIENTS AND METHODS: The study prospectively accrued colorectal
      cancer patients (n=106) completely resected and adjuvantly treated with FU and
      oxaliplatin according to the FOLFOX4 regimen (infusional FU, folinic acid, and
      oxaliplatin). Serial measurements were made of systolic and diastolic features of
      the left ventricle by radionuclide ventriculography, plasma levels of N-terminal
      pro-brain natriuretic peptide (NT-proBNP), lactic acid, and ECG before
      chemotherapy, immediately after a treatment infusion, and at follow-up 2 weeks
      after cessation of the intended 12 treatment courses and were further evaluated
      by multivariate regression analysis that included cardiovascular history and its
      risk factors. RESULTS: In the entire cohort, NT-proBNP significantly increased
      from baseline 14.5+/-3.2 pmol/L (mean+/-standard error) to 28.3+/-5.3 pmol/L
      during FU therapy (P<.001). Nine patients (8.5%) with cardiotoxicity had
      significantly higher NT-proBNP of 55.3+/-40.8 pmol/L compared with 25.4+/-4.1
      pmol/L in those without (P<.001). In multivariate analysis, the FU-induced rise
      of NT-proBNP was significantly higher in females (P<.001). Plasma lactic acid
      significantly increased from baseline (1.3+/-0.1 mmol/L to 1.8+/-0.1 mmol/L)
      during FU therapy (P<.001). Left ventricular ejection fraction at baseline of
      0.66+/-0.01 remained unchanged at 0.65+/-0.01 during FU therapy and 0.66+/-0.01
      at follow-up (P=.4). CONCLUSION: FU therapy generally induces myocardial
      neuroendocrine changes with increasing plasma NT-proBNP and lactic acid but
      without long-term dysfunction of the left ventricle. The usability of NT-proBNP
      as a predictive marker for FU cardiotoxicity remains to be clarified.

PMID- 21079149
TI  - Irf8 regulates macrophage versus neutrophil fate during zebrafish primitive
      myelopoiesis.
AB  - In vertebrates, myeloid cells comprise polymorphonuclear and mononuclear lineages
      that arise from 2 successive waves of development: a transitory primitive wave
      giving rise to limited myeloid cells during embryonic stage and a definitive wave
      capable of producing myeloid cells throughout the fetal and adult life. One key
      unresolved question is what factors dictate polymorphonuclear versus mononuclear
      lineage fates during myelopoiesis. Here we show that during zebrafish
      embryogenesis interferon regulatory factor-8 (irf8) is expressed specifically in
      macrophages but not neutrophils. Suppression of Irf8 function in zebrafish causes
      a depletion of macrophages and an enhanced output of neutrophils but does not
      affect the overall number, proliferation, and survival of primitive myeloid
      cells. These data indicate that the skewed myeloid lineage development in Irf8
      knockdown embryos results from a cell-fate switching. Such a conclusion is
      further supported by the observation showing that overexpression of Irf8 promotes
      macrophage formation at the expense of neutrophil development. Genetic epistasis
      analysis reveals that Irf8 acts downstream of Pu.1 but is insufficient to promote
      macrophage development in the absence of Pu.1. Our findings demonstrate that Irf8
      is a critical determinant for neutrophil versus macrophage fate choice during
      zebrafish primitive myelopoiesis.

PMID- 21079150
TI  - Constitutive reductions in mTOR alter cell size, immune cell development, and
      antibody production.
AB  - Mammalian TOR (mTOR) regulates cell growth, proliferation, and migration. Because
      mTOR knock-outs are embryonic lethal, we generated a viable hypomorphic mouse by
      neo-insertion that partially disrupts mTOR transcription and creates a potential
      physiologic model of mTORC1/TORC2 inhibition. Homozygous knock-in mice exhibited
      reductions in body, organ, and cell size. Although reductions in most organ sizes
      were proportional to decreased body weight, spleens were disproportionately
      smaller. Decreases in the total number of T cells, particularly memory cells, and
      reduced responses to chemokines suggested alterations in T-cell
      homing/homeostasis. T-cell receptor-stimulated T cells proliferated less,
      produced lower cytokine levels, and expressed FoxP3. Decreased neutrophil numbers
      were also observed in the spleen, despite normal development and migration in the
      bone marrow. However, B-cell effects were most pronounced, with a partial block
      in B-cell development in the bone marrow, altered splenic populations, and
      decreases in proliferation, antibody production, and migration to chemokines.
      Moreover, increased AKT(Ser473) phosphorylation was observed in activated B
      cells, reminiscent of cancers treated with rapamycin, and was reduced by a DNA-pk
      inhibitor. Thus, mTOR is required for the maturation and differentiation of
      multiple immune cell lineages. These mice provide a novel platform for studying
      the consequences of constitutively reduced mTORC1/TORC2 activity.

PMID- 21079151
TI  - Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is
      implicated in suppressing T-cell immunity in normal and pathologic settings.
      Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists
      not only in patients with cancer but also in healthy persons. We show that the
      presence of such IDO-specific CD8(+) T cells boosted T-cell immunity against
      viral or tumor-associated antigens by eliminating IDO(+) suppressive cells. This
      had profound effects on the balance between interleukin-17 (IL-17)-producing
      CD4(+) T cells and regulatory T cells. Furthermore, this caused an increase in
      the production of the proinflammatory cytokines IL-6 and tumor necrosis factor
      alpha while decreasing the IL-10 production. Finally, the addition of IDO
      inducing agents (ie, the TLR9 ligand cytosine-phosphate-guanosine, soluble
      cytotoxic T lymphocyte-associated antigen 4, or interferon gamma) induced IDO
      specific T cells among peripheral blood mononuclear cells from patients with
      cancer as well as healthy donors. In the clinical setting, IDO may serve as an
      important and widely applicable target for immunotherapeutic strategies in which
      IDO plays a significant regulatory role. We describe for the first time effector
      T cells with a general regulatory function that may play a vital role for the
      mounting or maintaining of an effective adaptive immune response. We suggest
      terming such effector T cells "supporter T cells."

PMID- 21079152
TI  - Somatic KRAS mutations associated with a human nonmalignant syndrome of
      autoimmunity and abnormal leukocyte homeostasis.
AB  - Somatic gain-of-function mutations in members of the RAS subfamily of small
      guanosine triphosphatases are found in > 30% of all human cancers. We recently
      described a syndrome of chronic nonmalignant lymphadenopathy, splenomegaly, and
      autoimmunity associated with a mutation in NRAS affecting hematopoietic cells,
      and initially we classified the disease as a variant of the autoimmune
      lymphoproliferative syndrome. Here, we demonstrate that somatic mutations in the
      related KRAS gene can also be associated with a nonmalignant syndrome of
      autoimmunity and breakdown of leukocyte homeostasis. The activating KRAS mutation
      impaired cytokine withdrawal-induced T-cell apoptosis through the suppression of
      the proapoptotic protein BCL-2 interacting mediator of cell death and facilitated
      proliferation through p27(kip1) down-regulation. These defects could be corrected
      in vitro by mitogen-activated protein kinase/extracellular signal-regulated
      kinase kinase 1 or phosphatidyl inositol-3 kinase inhibition. We suggest the use
      of the term RAS-associated autoimmune leukoproliferative disease to differentiate
      this disorder from autoimmune lymphoproliferative syndrome.

PMID- 21079153
TI  - Hematogones: a new prognostic factor for acute myeloblastic leukemia.
AB  - Acute myeloid leukemia (AML) patient outcomes remain heterogeneous, and new
      prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are
      normal B-lymphocyte precursors, which increase in number in hematologic diseases.
      The prognostic impact of the presence of detectable HGs on the leukemia-free
      survival (LFS) and overall survival of 120 consecutive patients with AML in first
      complete remission was investigated by flow cytometry. Patients who had HG levels
      more than 0.01% had a significantly better median LFS (29.2 vs 11.7 months; P =
      .001) and overall survival (not reached vs 23.5 months; P = .011). According to
      Cox analysis, an HG level more than 0.01% was an independent predictor of LFS
      (hazard ratio = 0.5; 95% confidence interval, 0.28-0.90, P < .03) when age,
      leukocytosis, the number of chemotherapy cycles, and the standardized cytogenetic
      and molecular risk subgroups were controlled for. These results indicate that HG
      analysis may help to define the risk of relapse in AML patients.

PMID- 21079154
TI  - BEACOPP chemotherapy is a highly effective regimen in children and adolescents
      with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group.
AB  - Dose-intensified treatment strategies for Hodgkin lymphoma (HL) have demonstrated
      improvements in cure but may increase risk for acute and long-term toxicities,
      particularly in children. The Children's Oncology Group assessed the feasibility
      of a dose-intensive regimen, BEACOPP (bleomycin, etoposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, prednisone) in children with high
      risk HL (stage IIB or IIIB with bulk disease, stage IV). Rapidity of response was
      assessed after 4 cycles of BEACOPP. Rapid responders received consolidation
      therapy with guidelines to reduce the risk of sex-specific long-term toxicities
      of therapy. Females received 4 cycles of COPP/ABV (cyclophosphamide, vincristine,
      procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) without involved
      field radiation therapy (IFRT). Males received 2 cycles of ABVD (doxorubicin,
      bleomycin, vinblastine, and dacarbazine) with IFRT. Slow responders received 4
      cycles of BEACOPP and IFRT. Ninety-nine patients were enrolled. Myelosuppression
      was frequent. Rapid response was achieved by 74% of patients. Five-year event
      free-survival is 94%, IFRT with median follow-up of 6.3 years. There were no
      disease progressions on study therapy. Secondary leukemias occurred in 2
      patients. Overall survival is 97%. Early intensification followed by less intense
      response-based therapy for rapidly responding patients is an effective strategy
      for achieving high event-free survival in children with high-risk HL. This trial
      is registered at http://www.clinicaltrials.gov as #NCT00004010.

PMID- 21079156
TI  - Surgery for papillary thyroid carcinoma: is lobectomy enough?
AB  - OBJECTIVE: To further understanding of treatment of papillary thyroid carcinoma
      (PTC). DESIGN: The Surveillance, Epidemiology, and End Results Program database
      was searched for patients who had undergone surgery for PTC. SETTING: Areas
      covered by Surveillance, Epidemiology, and End Results population-based
      registries. PATIENTS: Patients who had undergone PTC surgery between January 1,
      1988, and December 31, 2001, were included in the study. MAIN OUTCOME MEASURES:
      Disease-specific survival (DSS) and overall survival (OS). RESULTS: Of the total
      22,724 patients with PTC, 5964 patients underwent lobectomy. There were 2138
      total and 471 disease-specific deaths. Controlling for tumor size, multivariate
      analysis revealed no survival difference between patients who had undergone total
      thyroidectomy and those who had undergone lobectomy. Increased tumor size,
      extrathyroidal extent, positive nodal status, and increased age displayed
      significantly worse DSS and OS (P < .001). Histologically, follicular PTC subtype
      did not affect DSS or OS. Patients who had received radioactive iodine had poorer
      DSS but improved OS. Patients undergoing external beam radiation therapy had poor
      DSS (hazard ratio, 4.48; 95% confidence interval, 3.30-6.06; P < .001) and OS
      (1.71; 1.42-2.07; P < .001). CONCLUSIONS: The results of this study compel us to
      reinvestigate the current PTC surgical recommendations of total thyroidectomy
      based on tumor size because this may not affect survival across all populations.
      In addition, the current use of external beam radiation therapy for the treatment
      of PTC should be reexamined.

PMID- 21079155
TI  - Chronic lymphocytic leukemia cells receive RAF-dependent survival signals in
      response to CXCL12 that are sensitive to inhibition by sorafenib.
AB  - The chemokine CXCL12, via its receptor CXCR4, promotes increased survival of
      chronic lymphocytic leukemia (CLL) B cells that express high levels of zeta-chain
      associated protein (ZAP-70), a receptor tyrosine kinase associated with
      aggressive disease. In this study, we investigated the underlying molecular
      mechanisms governing this effect. Although significant differences in the
      expression or turnover of CXCR4 were not observed between ZAP-70(+) and ZAP-70(-)
      cell samples, CXCL12 induced greater intracellular Ca(2+) flux and stronger and
      more prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and
      mitogen-activated protein kinase/ERK kinase (MEK) in the ZAP-70(+) CLL cells. The
      CXCL12-induced phosphorylation of ERK and MEK in ZAP-70(+) CLL cells was blocked
      by sorafenib, a small molecule inhibitor of RAF. Furthermore, ZAP-70(+) CLL cells
      were more sensitive than ZAP-70(-) CLL cells to the cytotoxic effects of
      sorafenib in vitro at concentrations that can readily be achieved in vivo. The
      data suggest that ZAP-70(+) CLL cells may be more responsive to survival factors,
      like CXCL12, that are elaborated by the leukemia microenvironment, and this
      sensitivity could be exploited for the development of new treatments for patients
      with this disease. Moreover, sorafenib may have clinical activity for patients
      with CLL, particularly those with ZAP-70(+) CLL.

PMID- 21079157
TI  - Extent of surgery for papillary thyroid carcinoma: the debate continues: comment
      on "surgery for papillary thyroid carcinoma".

PMID- 21079158
TI  - Hearing loss and complaint in patients with head and neck cancer treated with
      radiotherapy.
AB  - OBJECTIVE: To investigate occurrences of hearing loss and hearing complaints
      among patients with head and neck tumors who underwent radiotherapy. DESIGN:
      Prospective case-control study. SETTING: Tertiary care hospital. PARTICIPANTS:
      Two hundred eighty-two participants underwent evaluation, including 141 with head
      and neck tumors and 141 as an age-matched control group. The controls had never
      undergone oncological treatment that put their hearing at risk. MAIN OUTCOME
      MEASURES: Results of audiological evaluation, including the Hearing Handicap
      Inventory for the Elderly questionnaire and pure-tone, speech, and immittance
      audiometry, and radiation dose received by the auditory system (based on the
      percentage of the external auditory canal included in the radiation field).
      RESULTS: We observed occurrences of hearing loss in 102 (72.3%) of the
      participants exposed to radiotherapy and 69 (48.9%) of the control group (P <
      .001). Hearing losses were mostly sensorineural and of mild degree, but those
      exposed to radiotherapy more frequently presented with severe and mixed-type
      hearing losses (P < .001). Of the participants exposed to radiotherapy, 19.1% had
      a severe handicap (P < .001). CONCLUSION: Patients undergoing radiotherapy in the
      head and neck region have a higher incidence of hearing loss and more severe
      hearing handicap. Trial Registration  clinicaltrials.gov Identifier: NCT01102621.

PMID- 21079159
TI  - Neck dissection after chemoradiotherapy: timing and complications.
AB  - OBJECTIVES: To determine the incidence of postchemoradiotherapy (post-CRT) neck
      dissection (ND) complications; to ascertain whether timing (< 12 vs >= 12 weeks)
      from CRT to ND or other factors are associated with increased complications; and
      to determine whether ND timing influences disease control or survival. DESIGN:
      Ten-year retrospective analysis. SETTING: Tertiary care center. PATIENTS: One
      hundred five patients with head and neck cancer undergoing ND after CRT. MAIN
      OUTCOME MEASURES: Complications and survival variables compared between groups
      undergoing ND less than 12 weeks (less-than-12-weeks ND group) and 12 weeks or
      more (12-weeks-or-more ND group) after CRT. RESULTS: Sixty-seven NDs were
      performed less than 12 weeks and 38 were performed 12 weeks or more after CRT.
      Patient characteristics, treatment, and ND pathology results were comparable
      between the 2 ND groups. The incidence of complications between the less-than-12
      weeks and the 12-weeks-or-more ND groups included major wound complications in 8
      of 67 (11.9%) vs 1 of 38 (2.6%; P = .15), minor wound complications in 11 of 67
      (16.4%) vs 4 of 38 (10.5%; P = .56), airway complications in 7 of 67 (10.4%) vs 2
      of 38 (5.3%; P = .48), and systemic complications in 9 of 67 (13.4%) vs 2 of 38
      (5.3%; P = .32). The number of patients with at least 1 complication was
      significantly smaller in the 12-weeks-or-more ND group (P = .04). Multivariate
      analysis showed that radical ND was significantly associated with an increased
      number of complications, and higher radiation doses approached significance (P =
      .05). Induction chemotherapy was associated with fewer wound complications (P =
      .01). There were no significant differences in overall survival (P = .82),
      progression-free survival (P = .77), or regional relapse (P = .54) between
      groups. Positive ND findings were associated with diminished progression-free and
      overall survival. CONCLUSION: These findings indicate that ND can be safely
      performed 12 weeks or more after CRT without adversely affecting surgical
      complications or survival variables.

PMID- 21079161
TI  - To TORS or Not to TORS: but is that the question? Comment on "transoral robotic
      surgery for advanced oropharyngeal carcinoma".

PMID- 21079160
TI  - Transoral robotic surgery for advanced oropharyngeal carcinoma.
AB  - OBJECTIVES: To determine the oncologic and functional outcomes in patients
      undergoing primary transoral robotic surgery followed by adjuvant therapy as
      indicated with a minimum of 18-month follow-up for advanced oropharyngeal
      carcinoma. DESIGN: Prospective single-center cohort study. SETTING: Academic
      university health system and tertiary referral center. PATIENTS: Forty-seven
      adults with newly diagnosed and previously untreated advanced oropharyngeal
      carcinoma. INTERVENTION: Transoral robotic surgery with staged neck dissection
      and adjuvant therapy as indicated. MAIN OUTCOME MEASURES: Margin status,
      recurrence, disease-specific and disease-free survival, gastrostomy tube
      dependence, and safety and efficacy end points. RESULTS: In the 47 patients
      enrolled with stages III and IV advanced oropharyngeal carcinoma, mean follow-up
      was 26.6 months. There was no intraoperative or postoperative mortality.
      Resection margins were positive in 1 patient (2%). At last follow-up, local
      recurrence was identified in 1 patient (2%), regional recurrence in 2 (4%), and
      distant recurrence in 4 (9%). Disease-specific survival was 98% (45 of 46
      patients) at 1 year and 90% (27 of 30 patients) at 2 years. Based on pathologic
      risk stratification, 18 of 47 patients (38%) avoided chemotherapy, and 5 patients
      (11%) did not receive adjuvant radiotherapy and concurrent chemotherapy in their
      treatment regimen. At minimum follow-up of 1 year, only 1 patient required a
      gastrostomy tube. CONCLUSIONS: This novel transoral robotic surgery treatment
      regimen offers disease control, survival, and safety commensurate with standard
      treatments and an unexpected beneficial outcome of gastrostomy dependency rates
      that are markedly lower than those reported with standard nonsurgical therapies.

PMID- 21079162
TI  - Ultrasonographic evaluation of sinusitis during microgravity in a novel animal
      model.
AB  - OBJECTIVES: To develop an animal model of rhinosinusitis in microgravity, to
      characterize the behavior of intracavitary fluid in microgravity, and to assess
      the accuracy of ultrasonographic (US) diagnosis in microgravity. DESIGN: An
      animal model of acute sinusitis was developed in anesthetized swine by creating a
      window into a frontal sinus to allow unilateral catheter placement and injection
      of fluid. We performed US examinations in normal and microgravity environments on
      control and sinusitis conditions and recorded these for later interpretation.
      SETTING: Henry Ford Hospital and the National Aeronautics and Space
      Administration (NASA) Microgravity Research Facility in Houston, Texas. SUBJECTS:
      Ground (normal-gravity) experiments were conducted on anesthetized swine (n = 4)
      at Henry Ford Hospital before the microgravity experiments (n = 4) conducted in
      the NASA Microgravity Research Facility. MAIN OUTCOME MEASURE: Ultrasound
      visualization of fluid cavity. RESULTS: Results of bilateral US examinations
      before fluid injection demonstrated typical air-filled sinuses. After unilateral
      injection of 1 mL of fluid, a consistent air-fluid interface was observed on the
      catheterized side at ground conditions. Microgravity conditions caused the rapid
      (<10-second) dissolution of the air-fluid interface, associated with uniform
      dispersion of the fluid to the walls of the sinus. The air-fluid interface
      reformed on return to normal gravity. CONCLUSIONS: The US appearance of fluid in
      nasal sinuses during microgravity is characterized in the large animal model. On
      the introduction of microgravity, the typical air-fluid interface disassociates,
      and fluid lining the sinus can be observed. Such fluid behavior can be used to
      develop diagnostic criteria for acute bacterial rhinosinusitis in the
      microgravity environment.

PMID- 21079163
TI  - Safety of a preservative-free acidified saline nasal spray: a randomized, double
      blind, placebo-controlled, crossover clinical trial.
AB  - OBJECTIVE: To determine the safety and tolerance of a buffered preservative-free
      acidified solution as an alternative to standard chemical preservatives to
      prevent microbial contamination of saline nasal spray. DESIGN: Randomized, double
      blind, placebo-controlled, crossover clinical trial. SETTING: Tertiary academic
      medical center. PARTICIPANTS: Healthy volunteers with no history or signs of
      sinonasal disease. INTERVENTIONS: Twenty volunteers used a buffered preservative
      free acidified solution in a saline nasal spray and a benzalkonium chloride
      containing saline nasal spray for 1 week each, separated by a 1-week washout
      period. MAIN OUTCOME MEASURES: At study enrollment and after using each nasal
      spray solution, participants completed a visual analog scale symptom
      questionnaire and the 20-Item Sino-Nasal Outcome Test and underwent nasal
      endoscopic examination, which was graded using a modified Lund-Kennedy scoring
      system. At the end of each test period, the contents of each nasal spray bottle
      were cultured for microorganism growth. RESULTS: All 20 participants completed
      the study. Four participants who developed upper respiratory tract illnesses
      during the study period were excluded from secondary analyses. No differences
      were observed in specific sinonasal symptoms or nasal endoscopy findings after
      use of either nasal spray. No nasal spray solutions from either group had any
      microorganism growth. CONCLUSION: In a short-term study with a small sample size,
      a preservative-free acidified solution seems to be safe and well tolerated, while
      maintaining sterility in a multiple-dose applicator without use of chemical
      preservatives.

PMID- 21079164
TI  - Objective measurements using the skin prick test in allergic rhinitis.
AB  - OBJECTIVE: To objectively measure the change in size of the wheal or erythema
      resulting from the skin prick test. DESIGN: Prospective randomized trial
      involving patients with allergic rhinitis recruited from March 8, 2009, through
      August 21, 2009, in Seoul, South Korea. SETTING: Otorhinolaryngology clinic of a
      university hospital. PATIENTS: Of 69 patients suspected of having allergic
      rhinitis, 46 with positive skin prick test results were selected. MAIN OUTCOME
      MEASURES: Skin prick test and Minolta CR-400 Chromameter. RESULTS: Comparing the
      2 values, as the size of the wheal or erythema increased, there was also an
      increase in the L*, a*, and b* values (P = .049 for each). CONCLUSIONS: Use of
      the Minolta CR-400 Chromameter provides an objective measure of the change in the
      size of the wheal or erythema. This method may be used in the clinical setting to
      improve the interpretation of skin prick testing results.

PMID- 21079165
TI  - Radiographic and anatomic characterization of the nasal septal swell body.
AB  - OBJECTIVE: To analyze the radiographic, anatomic, and histologic characteristics
      of the nasal septal swell body. DESIGN: Computer-aided analysis of magnetic
      resonance images (MRIs) and histologic examination of cadaveric nasal septa.
      SETTING: Tertiary medical center. PATIENTS: Fifty-four head MRI studies were
      performed on adult live patients; we also used 10 cadaveric nasal septa. MAIN
      OUTCOME MEASURES: Radiographic dimensions of the swell body and distances to
      other nasal landmarks were measured. Nasal septa and swell body histologic
      characteristics were evaluated using light microscopy. Relative proportions of
      vascular, connective, and glandular tissues within the swell body and the
      adjacent septum were compared. RESULTS: The swell body was fusiform shaped and
      located anterior to the middle turbinate, with mean (SD) width of 12.4 (1.9) mm;
      height, 19.6 (3.2) mm; and length, 28.4 (3.5) mm. The epicenter was 24.8 (2.9) mm
      from the nasal floor, 43.9 (4.1) mm from the nasal tip, and 39.0 (4.6) mm from
      the sphenoid face. Histologic analyses revealed that, compared with adjacent
      septal mucosa, the swell body contained significantly more venous sinusoids (37%
      vs 16%, P < .001) and fewer glandular elements (28% vs 41%, P < .001).
      CONCLUSIONS: The swell body is a conserved region of the septum located anterior
      to the middle turbinate approximately 2.5 cm above the nasal floor. The high
      proportion of venous sinusoids within the swell body suggests the capacity to
      alter nasal airflow. Additional study is required before these findings are used
      in a clinical setting.

PMID- 21079166
TI  - Oropharyngeal stenosis: a complication of multilevel, single-stage upper airway
      surgery in children.
AB  - OBJECTIVES: To describe oropharyngeal stenosis (OPS), a potential complication of
      multilevel, single-stage upper airway surgery involving lingual tonsillectomy in
      children, and to discuss the manner in which OPS may be managed successfully.
      DESIGN: Case series with an average follow-up of 12 months. SETTING: Tertiary
      care children's hospital. PATIENTS: Medical charts were reviewed for 104 patients
      who underwent lingual tonsillectomy over a 30-month period from January 1, 2007,
      to June 30, 2009. INTERVENTION: Multilevel, single-stage upper airway surgery,
      including lingual tonsillectomy. MAIN OUTCOME MEASURE: Development of OPS noted
      during office or intraoperative examination. RESULTS: Forty-nine of 104 patients
      underwent multilevel, single-stage upper airway procedures that included lingual
      tonsillectomy. Four of these 49 patients developed OPS, for a complication rate
      of 8.2%. Three patients required pharyngoplasty (scar release, debulking of
      fibrotic tissue, and reorientation of the scar) and triamcinolone injections in
      the operating room. A fourth patient underwent simple scar release in the
      operating room. No patient who underwent lingual tonsillectomy alone or in
      combination with an additional procedure at the same level of the upper airway
      developed OPS. CONCLUSIONS: Oropharyngeal stenosis is a potential complication of
      multilevel, single-stage upper airway surgery involving lingual tonsillectomy in
      children. Although there is pressure to perform multilevel procedures that
      address each site of upper airway obstruction in 1 sitting, this case series
      suggests the need for a more conservative, staged approach if lingual
      tonsillectomy is planned.

PMID- 21079167
TI  - Variation of patterns of malocclusion by site of pharyngeal obstruction in
      children.
AB  - OBJECTIVE: To correlate the type of dental occlusion and the type of pharyngeal
      lymphoid tissue obstruction in children. DESIGN: Cross-sectional study. SETTING:
      Ambulatory ear, nose, and throat clinic of Faculdade de Medicina da Universidade
      de Sao Paulo. PATIENTS: One hundred fourteen children aged 3 to 12 years
      presenting with mouth breathing and snoring due to tonsil and/or adenoid
      enlargement. INTERVENTIONS: Oroscopy and nasal fiber pharyngoscopy complemented
      by lateral head radiography to diagnose the type of obstruction, and clinical
      examination to evaluate the dental occlusion. MAIN OUTCOME MEASURES: Tonsil and
      adenoid obstruction (classified from grades 1-4) and sagittal, transverse, and
      vertical evaluation of dental occlusion. RESULTS: Obstructive enlargement of both
      tonsils and adenoids was detected in 64.9% of the sample; isolated enlargement of
      the adenoids, in 21.9%; isolated enlargement of the palatine tonsils, in 7.0%;
      and nonobstructive tonsils and adenoids, in 6.1%. All types of pharyngeal
      obstruction were related to a high prevalence of posterior crossbite (36.8%).
      Statistically significant association was found between sagittal dental occlusion
      and the site of lymphoid tissue obstruction (P = .02). A higher rate of class II
      relationship (43.2%) was detected in the group with combined adenoid and tonsil
      obstructive enlargement. Isolated tonsil obstruction showed a higher rate of
      class III relationship (37.5%). CONCLUSIONS: Different sites of obstruction of
      the upper airway due to enlarged lymphoid tissue are associated with different
      types of dental malocclusion. Findings are relevant to orthodontic and surgical
      decision making in these mouth-breathing patients.

PMID- 21079168
TI  - Otologic features in children with primary ciliary dyskinesia.
AB  - OBJECTIVES: To analyze otologic features in patients with primary ciliary
      dyskinesia (PCD) aged 0 to 18 years and to evaluate the correlation between
      ultrastructural defects and severity of otologic features. DESIGN: Retrospective
      study. SETTING: Pediatric referral center. PATIENTS: Fifty-eight patients with
      PCD were evaluated in the following 4 age intervals: group 1, preschool (<= 5
      years [n = 47]); group 2, school (6-11 years [n = 50]); group 3, teenagers (12-17
      years [n = 34]); and group 4, young adults (>= 18 years; 27 years for the oldest
      [n = 10]). Follow-up was 2 to 6 years in each age group; 26 patients had total
      follow-up of more than 12 years. Ultrastructural defects occurred in the outer
      dynein arm (n = 33), the inner dynein arm (n = 13), and the central complex (n =
      11). One patient had typical Kartagener syndrome with typical PCD features but
      normal ciliary ultrastructure. MAIN OUTCOME MEASURES: Frequency of acute otitis
      media, otitis media with effusion, otorrhea, chronic otitis media, hearing loss,
      and middle ear surgery and type of antibiotic regimen according to age and type
      of defect. RESULTS: Recurrent acute otitis media decreased from group 1 (32 of 47
      [68%]) to group 4 (0 of 10 [0%]) (P < .001). Otitis media with effusion was more
      severe in groups 1 through 3 than in group 4 (P = .02). Otorrhea decreased in
      group 4: 30% vs 80% (3 of 10 vs 36 of 41) in the other groups (P < .001). Half of
      the patients with tympanostomy tubes eventually had tympanic perforation. Hearing
      loss was moderate in groups 1 through 3 and mild in group 4. Continuous
      antibiotic therapy could be slightly reduced only in group 4. Central complex
      defect was a significant marker of severity for all these criteria. CONCLUSIONS:
      Despite continuous antibiotic therapy, the middle ear condition in PCD remained
      severe throughout childhood, with improvement only after age 18 years. Armstrong
      grommet placement did not improve the middle ear condition. Central complex
      defect is a marker of severity.

PMID- 21079169
TI  - Effect of apolactoferrin on experimental pneumococcal otitis media.
AB  - OBJECTIVE: To find the effect of apolactoferrin administration on the middle and
      inner ears after experimentally induced pneumococcal otitis media. DESIGN:
      Histopathologic and morphometric analysis of the middle and inner ears. SETTING:
      University of Minnesota, Minneapolis. SUBJECTS: Ten chinchillas. INTERVENTIONS:
      The middle ear cavities of chinchillas were inoculated bilaterally with type 2
      wild-type Streptococcus pneumoniae. Twenty-four hours later, the ears of 5 of the
      animals were injected with phosphate-buffered saline (PBS) and the other 5 with
      human apolactoferrin. The animals were killed 24 hours after the last injection.
      Bacterial counts were made of the middle ear effusions, and the cochleae were
      processed for histologic analysis. The thickness of the round window membranes
      and bacterial and inflammatory cell infiltration of the round window membranes,
      and scala tympani and damage of the hair cells and stria vascularis were compared
      for these 2 groups of animals. MAIN OUTCOME MEASURES: Comparison of inflammatory
      and bacterial cells in the middle and inner ears, and damage to inner ear
      structures. RESULTS: Bacterial plate counts of middle ear effusions (P  = .005)
      and the number of inflammatory cells in the round window membrane (P  = .047)
      were significantly lower in the apolactoferrin group compared with the group
      treated with PBS. CONCLUSION: Further investigation of apolactoferrin as a
      nonantibiotic approach for the treatment of otitis media and its complications is
      needed to confirm its safety and efficacy.

PMID- 21079170
TI  - Sarcoidosis masquerading as carotid body tumor.

PMID- 21079171
TI  - Traumatic impact to bone-anchored hearing aid resulting in epidural hematoma.

PMID- 21079172
TI  - Radiology quiz case 1. Pneumosinus dilatans (PSD) of the sphenoid sinus.

PMID- 21079173
TI  - Radiology quiz case 2. Lobular capillary hemangioma (LCH).

PMID- 21079174
TI  - Pathology quiz case 1. Cemento-ossifying fibroma (COF).

PMID- 21079175
TI  - Pathology quiz case 2. Primary signet ring carcinoma of the eyelid.

PMID- 21079176
TI  - Longitudinal aspect of case-control analysis.

PMID- 21079177
TI  - Teaching NeuroImages: long-term outcome of untreated Rasmussen syndrome.

PMID- 21079178
TI  - Modafinil is not the new caffeine.

PMID- 21079179
TI  - Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury.
AB  - BACKGROUND: Excessive daytime sleepiness (EDS) and fatigue are common symptoms
      after traumatic brain injury (TBI), but there is no specific treatment for
      affected patients. With this pilot study, we aimed at studying the effect of
      daily modafinil on posttraumatic EDS and fatigue. METHODS: We conducted a
      prospective, double-blind, randomized, placebo-controlled pilot study in 20
      patients with TBI who had fatigue or EDS or both. After baseline examinations
      (questionnaires including the Epworth Sleepiness Scale to assess EDS and the
      Fatigue Severity Scale to assess fatigue, actigraphy, polysomnography,
      maintenance of wakefulness test, and psychomotor vigilance test), 10 patients
      received 100 to 200 mg modafinil every morning, and 10 patients were treated with
      placebo. After a 6-week treatment period, all examinations were repeated.
      RESULTS: EDS improved significantly in patients with TBI who were treated with
      modafinil, compared with the placebo group. Similarly, the ability to stay awake
      on the maintenance of wakefulness test improved only in the modafinil group.
      Modafinil, however, had no impact on posttraumatic fatigue. Clinically relevant
      side effects were not observed. CONCLUSION: This study indicates that modafinil
      is effective and well tolerated in the treatment of posttraumatic EDS but not of
      fatigue. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that
      modafinil (100-200 mg daily) improves posttraumatic EDS compared with placebo.
      This study provides Class I evidence that modafinil (100-200 mg daily) does not
      improve posttraumatic fatigue compared with placebo.

PMID- 21079180
TI  - GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort
      study.
AB  - BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may
      offer diagnostic and prognostic tools in addition to clinical indices. This study
      aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations
      in blood as outcome predictors of TBI using cutoff levels of 1.5 MUg/L for GFAP
      and 1.13 MUg/L for S100B from a previous study. METHODS: In 79 patients with TBI
      (Glasgow Coma Scale score [GCS] <=12), serum, taken at hospital admission, was
      analyzed for GFAP and S100B. Data collected included injury mechanism, age,
      gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS),
      presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow
      Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs
      favorable), 6 months post injury. RESULTS: In patients who died compared to alive
      patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold.
      In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and
      S100B 2.1-fold. Univariate logistic regression analysis revealed that mass
      lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia,
      predicted death and unfavorable outcome. Multivariable analysis showed that
      models containing mass lesion, pupils, GFAP, and S100B were the strongest in
      predicting death and unfavorable outcome. S100B was the strongest single
      predictor of unfavorable outcome with 100% discrimination. CONCLUSION: This study
      confirms that GFAP and S100B levels in serum are adjuncts to the assessment of
      brain damage after TBI and may enhance prognostication when combined with
      clinical variables.

PMID- 21079182
TI  - Vesicular glutamate transporter and cognition in stroke: a case-control autopsy
      study.
AB  - OBJECTIVES: Vascular dementia (VaD) accounts for approximately 15%-20% of all
      dementias, but the relationship of progressive cognitive impairment to
      neurochemical changes is poorly understood. We have therefore investigated
      glutamatergic synaptic markers in VaD. METHODS: We used homogenates prepared from
      gray matter from 2 neocortical regions (Brodmann area [BA] 9 and BA 20) and
      Western blotting to determine the concentrations of key components of the
      glutamatergic neurotransmitter system, vesicular glutamate transporter 1 (VGLUT1)
      and excitatory amino acid transporter EAAT2 (GLT-1), and the ubiquitous synaptic
      protein, synaptophysin, in 73 individuals-48 patients with cerebrovascular
      disease with and without dementia, 10 patients with AD, and 15 controls-in a case
      control design. RESULTS: VGLUT1 concentrations in BA 20 and BA 9 were correlated
      with CAMCOG total (Rs 0.525, p = 0.018, n = 20; Rs 0.560, p = 0.002, n = 27) and
      CAMCOG memory scores (Rs 0.616, p = 0.004, n = 20; Rs 0.675, p = 0.000, n = 27).
      VGLUT1 concentration in BA 9 differed between the different dementia groups and
      the stroke no dementia group (1-way analysis of variance F = 6.69, p = 0.001 and
      Bonferroni p < 0.01 in each case), with subjects with stroke who did not develop
      dementia exhibiting the highest mean value for VGLUT1. CONCLUSIONS: These data
      suggest that loss of glutamatergic synapses is a feature of VaD and Alzheimer
      disease but the preservation of synapses, in particular glutamatergic synapses,
      in the frontal cortex against the temporal cortex plays a role in sustaining
      cognition and protecting against dementia following a stroke.

PMID- 21079181
TI  - Pregnancy and fetal outcomes after interferon-beta exposure in multiple
      sclerosis.
AB  - OBJECTIVE: To assess pregnancy and fetal outcomes after in utero exposure to
      interferon-beta (IFNbeta) in all pregnancies occurring in women with multiple
      sclerosis (MS) during the study period, with a specific focus on the risk of
      spontaneous abortion. METHODS: In this cohort study, data were gathered through a
      standardized, semi-structured interview. Patients who discontinued IFNbeta less
      than 4 weeks from conception (exposed) were compared with those who had
      discontinued the drug at least 4 weeks from conception or who were never treated
      (not exposed). Possible confounders were handled through multivariate analyses
      adjusted for propensity score (PS). RESULTS: We collected data on 396 pregnancies
      in 388 women, 88 classified as exposed (mean exposure 4.6 +/- 5.8 weeks). IFNbeta
      exposure was not associated with an increased risk of spontaneous abortion (PS
      adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.4 to 2.9, p =
      0.88), although it was associated with both lower baby weight (PS-adjusted beta 
      113.8, p < 0.0001) and length (PS-adjusted beta -1.102, p < 0.0001). Proportion
      of spontaneous abortion in exposed patients fell within the range expected for
      the Italian population in the same period. IFNbeta exposure (PS-adjusted OR 2.11,
      95% CI 1.18 to 3.78, p = 0.012) and cesarean delivery were the only predictors of
      preterm delivery. In the exposed group, we did not observe any significant fetal
      complications, malformations, or developmental abnormalities over a median follow
      up of 2.1 years. CONCLUSIONS: Our findings point to the relative safety of
      IFNbeta exposure times of up to 4 weeks and can assist neurologists facing
      therapeutic decisions in women with MS with a pregnancy plan.

PMID- 21079183
TI  - Dietary intake of vitamin D and cognition in older women: a large population
      based study.
AB  - BACKGROUND: Serum vitamin D concentrations are associated with global cognitive
      function among older adults. The benefits of vitamin D intake to treat or prevent
      cognitive impairment remain unknown. The objective of this cross-sectional study
      was to determine whether weekly dietary intake of vitamin D could be associated
      with global cognitive performance among older adults. METHODS: A total of 5,596
      community-dwelling women (mean age 80.5 +/- 0.1 years) free of vitamin D drug
      supplements from the Epidemiologie de l'Osteoporose (EPIDOS) study were divided
      into 2 groups according to baseline weekly vitamin D dietary intake (either
      inadequate <35 MUg/wk or recommended >=35MUg/wk). Weekly vitamin D dietary
      intakes were estimated from a self-administered food frequency questionnaire.
      Cognitive impairment was defined as a Pfeiffer Short Portable Mental State
      Questionnaire (SPMSQ) score <8. Age, body mass index, sun exposure at midday,
      season, disability, number of chronic diseases, hypertension, depression, use of
      psychoactive drugs, and education level were considered as potential confounders.
      RESULTS: Compared to women with recommended weekly vitamin D dietary intakes (n =
      4,802; mean age 80.4 +/- 3.8 years), women with inadequate intakes (n = 794; mean
      age 81.0 +/- 3.8 years) had a lower mean SPMSQ score (p < 0.001) and more often
      had an SPMSQ score <8 (p = 0.002). We found an association between weekly vitamin
      D dietary intake and SPMSQ score (beta = 0.002, p < 0.001). Inadequate weekly
      vitamin D dietary intakes were also associated with cognitive impairment
      (unadjusted odds ratio = 1.42 with p = 0.002; full adjusted odds ratio = 1.30
      with p = 0.024). CONCLUSIONS: Weekly dietary intake of vitamin D was associated
      with cognitive performance in older women.

PMID- 21079184
TI  - Perceptual reasoning predicts handwriting impairments in adolescents with autism.
AB  - BACKGROUND: We have previously shown that children with autism spectrum disorder
      (ASD) have specific handwriting deficits consisting of poor form, and that these
      deficits are predicted by their motor abilities. It is not known whether the same
      handwriting impairments persist into adolescence and whether they remain linked
      to motor deficits. METHODS: A case-control study of handwriting samples from
      adolescents with and without ASD was performed using the Minnesota Handwriting
      Assessment. Samples were scored on an individual letter basis in 5 categories:
      legibility, form, alignment, size, and spacing. Subjects were also administered
      an intelligence test and the Physical and Neurological Examination for Subtle
      (Motor) Signs (PANESS). RESULTS: We found that adolescents with ASD, like
      children, show overall worse performance on a handwriting task than do age- and
      intelligence-matched controls. Also comparable to children, adolescents with ASD
      showed motor impairments relative to controls. However, adolescents with ASD
      differ from children in that Perceptual Reasoning Indices were significantly
      predictive of handwriting performance whereas measures of motor skills were not.
      CONCLUSIONS: Like children with ASD, adolescents with ASD have poor handwriting
      quality relative to controls. Despite still demonstrating motor impairments, in
      adolescents perceptual reasoning is the main predictor of handwriting
      performance, perhaps reflecting subjects' varied abilities to learn strategies to
      compensate for their motor impairments.

PMID- 21079186
TI  - Neural control of the bladder: recent advances and neurologic implications.

PMID- 21079185
TI  - Four novel cases of periaxin-related neuropathy and review of the literature.
AB  - OBJECTIVE: To report 4 cases of autosomal recessive hereditary neuropathy
      associated with novel mutations in the periaxin gene (PRX) with a review of the
      literature. Periaxin protein is required for the maintenance of peripheral nerve
      myelin. Patients with PRX mutations have early-onset autosomal recessive
      demyelinating Charcot-Marie-Tooth disease (CMT4F) or Dejerine-Sottas neuropathy
      (DSN). Only 12 different mutations have been described thus far. METHODS: Case
      reports and literature review. RESULTS: Four patients from 3 unrelated families
      (2 siblings and 2 unrelated patients) were affected by an early-onset, slowly
      progressive demyelinating neuropathy with relevant sensory involvement. All
      carried novel frameshift or nonsense mutations in the PRX gene. The 2 siblings
      were compound heterozygotes for 2 PRX null mutations (p.Q547X and p.K808SfsX2),
      the third patient harbored a homozygous nonsense mutation (p.E682X), and the last
      patient had a homozygous 2-nt insertion predicting a premature protein truncation
      (p.S259PfsX55). Electrophysiologic analysis showed a severe slowing of motor
      nerve conduction velocities (MNCVs, between 3 and 15.3 m/s) with undetectable
      sensory nerve action potentials (SNAPs). Sural nerve biopsy, performed in 2
      patients, demonstrated a severe demyelinating neuropathy and onion bulb
      formations. Interestingly, we observed some variability of disease severity
      within the same family. CONCLUSIONS: These cases and review of the literature
      indicate that PRX-related neuropathies have early onset but overall slow
      progression. Typical features are prominent sensory involvement, often with
      sensory ataxia; a moderate-to-dramatic reduction of MNCVs and almost invariable
      absence of SNAPs; and pathologic demyelination with classic onion bulbs, and less
      commonly myelin folding and basal lamina onion bulbs.

PMID- 21079187
TI  - Hemodialysis headache and presyrinx in spontaneous intracranial hypotension.

PMID- 21079188
TI  - Toothbrushing EEG artifact recorded from chronically implanted subdural
      electrodes.

PMID- 21079189
TI  - Right brain: we were all once "fixed and dilated".

PMID- 21079190
TI  - Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia: swift
      or sure? The acceptable rate of neurovascular mimics among IV tPA-treated
      patients.

PMID- 21079193
TI  - Racial differences in the association of pentraxin-3 with kidney dysfunction: the
      Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Pentraxin-3 (PTX3), an inflammatory marker thought to be related to
      vascular inflammation, is elevated in advanced chronic kidney disease (CKD).
      Whether PTX3 is associated with mild to moderate kidney dysfunction is unknown.
      METHODS: We tested associations of proteins in the pentraxin family [PTX3, C
      reactive protein (CRP) and serum amyloid protein (SAP)] with estimated glomerular
      filtration rate by cystatin C (eGFRcys) and microalbuminuria among 2824
      participants in the Multi-Ethnic Study of Atherosclerosis. Associations were
      tested using multivariable linear regression with adjustment for demographics
      (age, gender, annual income), comorbidities (diabetes, hypertension, smoking,
      body mass index, low-density lipoprotein, high-density lipoprotein,
      triglycerides, ACE inhibitor and statin use) and systemic inflammation
      [interleukin-6 (IL-6)]. RESULTS: Among the 2824 participants, mean age was 62
      years and mean eGFRcys was 94 mL/min/1.73 m(2); 25% were white, 25% Chinese, 25%
      African-American and 25% Hispanic. Among all participants after full adjustment,
      higher PTX3 was associated with lower eGFRcys independently of IL-6 (beta - 3.0
      mL/min/1.73 m(2) per unit increase in lnPTX3, P < 0.001). In contrast, CRP and
      SAP were associated with eGFRcys in demographic adjusted models, but these
      associations were attenuated after adjustment for comorbidities and IL-6 (lnCRP
      beta - 0.06, P = 0.9; lnSAP beta - 0.35, P = 0.7). There was a significant
      interaction with race/ethnicity (P < 0.001) in the association of PTX3 and
      eGFRcys. After adjustment for demographics, comorbidities and IL-6, this
      association was significant in blacks (beta - 5.7 mL/min/1.73 m(2) per unit
      increase in lnPTX3, P = 0.002) but not in Hispanics (beta - 2.4, P = 0.1),
      Chinese (beta - 0.91, P = 0.5) or whites (beta - 0.26, P = 0.9). PTX3 and CRP,
      but not SAP, had correlations with microalbuminuria in unadjusted models
      (Spearman coefficients PTX3 0.05, P = 0.005; CRP 0.07, P < 0.001; SAP 0.013, P =
      0.5), but these were attenuated after full adjustment. CONCLUSIONS: Endovascular
      inflammation may be an important mechanism associated with early kidney
      dysfunction, particularly among blacks. This mechanism appears to be independent
      of IL-6-regulated pathways.

PMID- 21079194
TI  - The treatment of hyperphosphataemia in CKD: calcium-based or calcium-free
      phosphate binders?

PMID- 21079195
TI  - Renal transplantation for nephrogenic systemic fibrosis: a case report and review
      of the literature.
AB  - Nephrogenic systemic fibrosis (NSF) is a rare fibrosing disorder described among
      patients with renal disease. Currently, no standard therapy exists, although
      therapeutic modalities have included plasmapheresis, extracorporeal
      photopheresis, sodium thiosulphate, imatinib and renal transplantation. We
      describe a patient with NSF who was physically debilitated and underwent renal
      transplantation. After transplantation, the patient's lesions improved
      clinically, and the patient was ambulatory. Despite developing worsening renal
      function, her lesions remained unchanged. We conclude that renal transplantation
      improves symptoms of NSF, and believe that in patients with NSF, careful
      consideration should be made for early renal transplantation.

PMID- 21079196
TI  - Proteomic analysis of peritoneal fluid of patients treated by peritoneal
      dialysis: effect of glucose concentration.
AB  - BACKGROUND: Depending on both membrane composition and solute transport rate
      across the membrane, protein composition of the dialysate of patients receiving
      peritoneal dialysis (PD) has recently become of great interest. Unfortunately,
      thus far few studies have focused on dialysate characterization, and further
      investigations are required to better understand the biological mechanisms
      influencing PD efficiency. METHODS: Different classical proteomic approaches were
      combined with advanced mass spectrometric (MS) techniques to analyse peritoneal
      fluid (PF) protein composition of adult patients receiving PD. Characterization
      was performed by using 1D gel electrophoresis combined with nano-RP-HPLC-ESI
      MS/MS and shotgun proteomics, while comparative analyses were performed coupling
      2D gel electrophoresis with MALDI-TOF MS. RESULTS: The study allowed the
      identification of 151 different proteins from PF, which are mainly of plasmatic
      origin. Comparison of PD effluents characterized by different glucose
      concentrations demonstrated four proteins (apolipoprotein A-IV, fibrinogen beta
      chain, transthyretin and alpha-1-antitrypsin) to be under-expressed in the
      highest osmolar solution having 4.25% compared to others having 1.5% and 2.5%
      glucose. All of them were found to be involved in the inflammatory processes.
      CONCLUSIONS: This study provides a possible platform for future diagnostic and
      therapeutic applications in the field of PD and allowed the identification of
      potential targets to be used in preventing inflammatory processes induced by the
      exposure to dialysis solutions.

PMID- 21079197
TI  - Temporal changes in the expression of mRNA of NADPH oxidase subunits in renal
      epithelial cells exposed to oxalate or calcium oxalate crystals.
AB  - BACKGROUND: Exposure of renal epithelial cells to oxalate (Ox) or calcium oxalate
      (CaOx) crystals leads to the production of reactive oxygen species and cell
      injury. We have hypothesized that Ox and CaOx crystals activate NADPH oxidase
      through upregulation of its various subunits. METHODS: Human renal epithelial
      derived cell line, HK-2, was exposed to 100 MUmol Ox or 66.7 MUg/cm(2) CaOx
      monohydrate crystals for 6, 12, 24 or 48 h. After exposure, the cells and media
      were processed to determine activation of NADPH oxidase, production of superoxide
      and 8-isoprostane (8IP), and release of lactate dehydrogenase (LDH). RT-PCR was
      performed to determine mRNA expression of NADPH subunits p22(phox), p40(phox),
      p47(phox), p67(phox) and gp91(phox) as well as Rac-GTPase. RESULTS: Exposure to
      Ox and CaOx crystals resulted in increase in LDH release, production of 8-IP,
      NADPH oxidase activity and production of superoxide. Exposure to CaOx crystals
      resulted in significantly higher NADPH oxidase activity, production of superoxide
      and LDH release than Ox exposure. Exposure to Ox and CaOx crystals altered the
      expression of various subunits of NADPH oxidase. More consistent were increases
      in the expression of membrane-bound p22(phox) and cytosolic p47(phox).
      Significant and strong correlations were seen between NADPH oxidase activity, the
      expression of p22(phox) and p47(phox), production of superoxide and release of
      LDH when cells were exposed to CaOx crystals. The expressions of neither
      p22(phox) nor p47(phox) were significantly correlated with increased NADPH
      oxidase activity after the Ox exposure. CONCLUSIONS: As hypothesized, exposure to
      Ox or CaOx crystals leads to significant increases in the expression of p22(phox)
      and p47(phox), leading to activation of NADPH oxidase. Increased NADPH oxidase
      activity is associated with increased superoxide production and lipid
      peroxidation. Different pathways appear to be involved in the stimulation of
      renal epithelial cells by exposure to Ox and CaOx crystals.

PMID- 21079198
TI  - Ruling out coronary artery disease with noninvasive coronary multidetector CT
      angiography before noncoronary cardiovascular surgery.
AB  - PURPOSE: To assess the usefulness of preoperative coronary computed tomographic
      (CT) angiography in the detection of coronary artery disease (CAD) in nonselected
      patients scheduled to undergo noncoronary cardiovascular surgery to avoid
      unnecessary invasive coronary angiography (ICA). MATERIALS AND METHODS: The
      institutional review board approved the study protocol; informed consent was
      given. This prospective study involved 161 consecutive patients who underwent
      coronary calcium scoring and coronary CT angiography before undergoing
      noncoronary cardiovascular surgery. Seven patients were excluded because of
      contraindications to CT angiography. The major indication of noncoronary
      cardiovascular surgery was valvular heart disease (121 patients). Follow-up was
      performed at a median of 20 months to define ischemic events described as acute
      coronary syndrome or death secondary to acute coronary syndrome, arrhythmias, or
      cardiac failure. Multivariate analysis was performed to determine predictors of
      nondiagnostic coronary CT angiography. Kaplan-Meier analysis was performed to
      evaluate outcome at follow-up. RESULTS: Twenty-one patients did not undergo
      surgery, which left 133 patients as the study group. Atrial fibrillation was
      present in 45 of 133 patients. The interquartile range of the Agatston coronary
      calcium score was 0-471. Coronary CT angiography was diagnostic in 108 of 133
      patients. Of these, 93 of 108 had no significant CAD (<= 50% stenosis), and
      noncoronary cardiovascular surgery was performed in them without preoperative
      ICA. No patients in this group had postoperative ischemic events at follow-up.
      Coronary CT angiography was nondiagnostic in 25 of 133 patients who were referred
      for preoperative ICA. Multivariate analysis showed Agatston score to be the only
      independent predictor of nondiagnostic coronary CT angiography (odds ratio =
      1.002; 95% confidence interval: 1.001, 1.003; P = .001). The best Agatston score
      cutoff for diagnostic coronary CT angiography was 579. CONCLUSION: In nonselected
      patients scheduled to undergo noncoronary cardiovascular surgery, preoperative
      coronary CT angiography was diagnostic in 81% of cases. Preoperative ICA could be
      safely avoided in patients without significant CAD by using coronary CT
      angiography. The Agatston score, but not the presence of atrial fibrillation, was
      an independent predictor of nondiagnostic coronary CT angiography. SUPPLEMENTAL
      MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100384/
      /DC1.

PMID- 21079199
TI  - Utility of 6-month follow-up imaging after a concordant benign breast biopsy
      result.
AB  - PURPOSE: To determine the utility of 6-month follow-up imaging after benign
      concordant image-guided percutaneous breast biopsy results. MATERIALS AND
      METHODS: The institutional review board approved this retrospective, HIPAA
      compliant study; informed consent was waived. Findings from consecutive
      stereotactic and ultrasonographically guided core breast biopsies performed from
      2001 to 2005 were analyzed and included lesions with benign pathologic findings
      without atypia found to be concordant with imaging at a consensus conference.
      Rebiopsy recommendation rates and positive predictive values (PPVs) for detecting
      malignancy at each follow-up interval were measured and compared by using a two
      tailed Fisher exact test. RESULTS: In 2244 biopsies, lesions in 1465 were benign,
      concordant, and not excised. In 1057 of 1465 (72.2%) biopsies with imaging follow
      up (average, 26.4 months; range, 4.0-49.9 months), recommended rebiopsy rates
      were 0.8% (four of 526), 0.5% (three of 588), and 1.0% (eight of 802) at 6-month,
      12-month, and long-term follow-up intervals, respectively. When the initial
      follow-up did not occur until 12 months, the recommended rebiopsy rate was 0.9%
      (three of 322), compared with 0.8% (four of 526) at 6 months (P > .99), and no
      malignancies were found in either group. One malignancy was detected at the long
      term follow-up interval (PPV for excision recommended, 12% [one of eight]; PPV
      for excision performed, 20% [one of five]). CONCLUSION: Because rebiopsy
      recommendation rates and PPVs did not differ in the 6- and 12-month groups, a 6
      month follow-up imaging examination, in the context of a formal concordancy
      consensus conference, may not contribute to improved breast cancer diagnosis.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10091824/-/DC1.

PMID- 21079200
TI  - Evaluation of an active vena cava filter for MR imaging in a swine model.
AB  - PURPOSE: To evaluate the feasibility of magnetic resonance (MR) imaging-guided
      placement of an active vena cava filter (AVCF) in a swine model, the
      effectiveness of the system in filtering thrombi, and the detection of thrombi
      with MR imaging. MATERIALS AND METHODS: This study was approved by the government
      committee on animal investigations. An AVCF tuned to the Larmor frequency of a
      1.5-T MR unit was placed in the inferior vena cava (IVC) of seven pigs under real
      time MR imaging guidance. Steady-state free precession sequences with four
      different flip angles (90 degrees , 40 degrees , 25 degrees , and 15 degrees ),
      T1-weighted turbo spin-echo sequences with two flip angles (90 degrees  and 15
      degrees ), and black-blood proton-density-weighted sequences with a flip angle of
      90 degrees  were performed before and after filter placement. In six cases,
      extracorporeally produced thrombi were injected through the femoral access to
      test filter function. The signal-to-noise ratio (SNR) and contrast-to-noise ratio
      (CNR) were assessed before and after filter deployment and compared by using the
      signed-rank test. RESULTS: All AVCFs were successfully deployed. Significant
      differences (P < .05) in the SNR and CNR of the IVC were found before and after
      AVCF placement and between sequences with different flip angles. Intravenous
      thrombi were caught in all cases and clearly depicted with MR imaging. On black
      blood proton-density-weighted images, high-signal-intensity thrombi inside the
      filter were clearly detectable without any overlaying artifacts. CONCLUSION: MR
      imaging-guided deployment and monitoring of an AVCF is feasible. The AVCF
      enhances the SNR and CNR, resulting in clear depiction of thrombi inside the
      filter without the need for contrast material. Design modifications for improved
      intracaval fixation and retrieval of the prototype AVCF will be required.

PMID- 21079201
TI  - T1-weighted fat-suppressed imaging of the pelvis with a dual-echo Dixon
      technique: initial clinical experience.
AB  - PURPOSE: To compare the image quality of water-only images generated from a dual
      echo Dixon technique with that of standard fast spin-echo T1-weighted chemical
      shift fat-suppressed images obtained in patients evaluated for pelvic pain with a
      1.5-T magnetic resonance (MR) system. MATERIALS AND METHODS: The ethics board
      granted approval for this retrospective study; patient consent was not required.
      Twenty-five women underwent both standard axial T1-weighted fast spin-echo
      chemical shift fat-suppressed imaging and dual-echo Dixon imaging of the pelvis.
      Two readers independently scored the acquisitions for image quality, fat
      suppression quality, and artifact. On the basis of signal intensity measurements,
      the uniformity of fat suppression, the contrast between fat-suppressed and non
      fat-suppressed tissue, and the contrast between pathologic lesions and suppressed
      fat were calculated. Values obtained with the T1-weighted fat-suppressed and dual
      echo Dixon techniques were compared by using the Wilcoxon signed rank test.
      RESULTS: The images generated with the dual-echo Dixon technique were of higher
      quality, had better fat suppression, and had less artifact (qualitative scores:
      4.4, 4.6, and 4.0, respectively) compared with the standard T1-weighted fat
      suppressed images (qualitative scores: 3.4, 3.3, and 3.6, respectively; P < .01).
      Contrast between fat-suppressed and non-fat-suppressed tissue (contrast ratio:
      0.86 for dual-echo Dixon technique vs 0.42 for T1-weighted fat-suppressed
      technique, P < .001) and between pathologic lesions and suppressed fat (contrast
      ratio: 0.88 for dual-echo Dixon technique vs 0.57 for T1-weighted fat-suppressed
      technique, P =.012) was significantly improved with the dual-echo Dixon
      technique. Twelve pathologic lesions were identified with dual-echo Dixon imaging
      versus eight that were identified with T1-weighted fat-suppressed imaging.
      CONCLUSION: Compared with standard T1-weighted fat-suppressed imaging, dual-echo
      Dixon imaging facilitates improved image quality of fat-suppressed images of the
      pelvis, enabling better delineation of pathologic lesions.

PMID- 21079202
TI  - Summaries for Patients: Daily application of dihydrotestosterone gel does not
      prevent age-related growth of the prostate gland.

PMID- 21079203
TI  - Summaries for patients: Characteristics of prescriptions that are abandoned at
      the pharmacy.

PMID- 21079204
TI  - Summaries for patients: International study of consent for kidney
      transplantation.

PMID- 21079205
TI  - ACP Journal Club. Intensifying glucose control and adding fenofibrate to
      simvastatin each reduced progression of retinopathy in type 2 diabetes.

PMID- 21079206
TI  - ACP Journal Club. Review: Fibrates reduce risk for cardiovascular outcomes.

PMID- 21079207
TI  - ACP Journal Club. Stenting and endarterectomy for carotid artery stenosis did not
      differ for a composite of stroke, MI, or death.

PMID- 21079208
TI  - ACP Journal Club. Early use of TIPS in patients with cirrhosis and variceal
      bleeding.

PMID- 21079209
TI  - ACP Journal Club. Early and late initiation of dialysis did not differ for
      reduction of all-cause mortality in stage 5 chronic kidney disease.

PMID- 21079210
TI  - ACP Journal Club. Review: Erythropoiesis-stimulating agents targeted to higher
      hemoglobin levels increase risk for adverse outcomes in CKD.

PMID- 21079211
TI  - ACP Journal Club. Review: Some drugs are effective for preventing migraine
      headache; limited evidence exists on the relative effectiveness of drugs.

PMID- 21079212
TI  - ACP Journal Club. Review: Aspirin reduces acute migraine pain in adults.

PMID- 21079213
TI  - ACP Journal Club. Adding steroid injection to exercise and manual mobilization
      did not reduce shoulder pain and disability over the long term.

PMID- 21079214
TI  - ACP Journal Club. Review: Calcium supplements increase risk for myocardial
      infarction but not mortality or stroke in adults.

PMID- 21079215
TI  - ACP Journal Club. Extended-duration enoxaparin reduced VTE but increased major
      bleeding in patients with acute medical illness.

PMID- 21079216
TI  - ACP Journal Club. Intensive glucose control did not reduce a composite of
      microvascular events more than standard control in type 2 diabetes.

PMID- 21079217
TI  - Long-term effects of dihydrotestosterone treatment on prostate growth in healthy,
      middle-aged men without prostate disease: a randomized, placebo-controlled trial.
AB  - BACKGROUND: Benign prostatic hypertrophy increases with age and can result in
      substantially decreased quality of life for older men. Surgery is often required
      to control symptoms. It has been hypothesized that long-term administration of a
      nonamplifiable pure androgen might decrease prostate growth, thereby decreasing
      or delaying the need for surgical intervention. OBJECTIVE: To test the hypothesis
      that dihydrotestosterone (DHT), a nonamplifiable and nonaromatizable pure
      androgen, reduces late-life prostate growth in middle-aged men. DESIGN:
      Randomized, placebo-controlled, parallel-group trial. (Australian New Zealand
      Clinical Trials Registry number: ACTRN12605000358640) SETTING: Ambulatory care
      research center. PARTICIPANTS: Healthy men (n = 114) older than 50 years without
      known prostate disease. INTERVENTION: Transdermal DHT (70 mg) or placebo gel
      daily for 2 years. MEASUREMENTS: Prostate volume was measured by ultrasonography;
      bone mineral density (BMD) and body composition were measured by dual-energy x
      ray absorptiometry; and blood samples and questionnaires were collected every 6
      months, with data analyzed by mixed-model analysis for repeated measures.
      RESULTS: Over 24 months, there was an increase in total (29% [95% CI, 23% to
      34%]) and central (75% [CI, 64% to 86%]; P < 0.01) prostate volume and serum
      prostate-specific antigen level (15% [CI, 6% to 24%]) with time on study, but DHT
      had no effect (P > 0.2). Dihydrotestosterone treatment decreased spinal BMD (1.4%
      [CI, 0.6% to 2.3%]; P < 0.001) at 24 months but not hip BMD (P > 0.2) and
      increased serum aminoterminal propeptide of type I procollagen in the second year
      of the study compared with placebo. Dihydrotestosterone increased serum DHT
      levels and its metabolites (5alpha-androstane-3alpha,17beta-diol and 5alpha
      androstane-3beta,17beta-diol) and suppressed serum testosterone, estradiol,
      luteinizing hormone, and follicle-stimulating hormone levels. Dihydrotestosterone
      increased hemoglobin levels (7% [CI, 5% to 9%]), serum creatinine levels (9% [CI,
      5% to 11%]), and lean mass (2.4% [CI, 1.6% to 3.1%) but decreased fat mass (5.2%
      [CI, 2.6% to 7.7%]) (P <0.001 for all). Protocol-specific discontinuations due to
      DHT were asymptomatic increased hematocrit (n = 8), which resolved after stopping
      treatment, and increased prostate-specific antigen levels (n = 3; none with
      prostate cancer) in the DHT group. No serious adverse effects due to DHT
      occurred. LIMITATION: Negative findings on prostate growth cannot exclude adverse
      effects on the natural history of prostate cancer. CONCLUSION:
      Dihydrotestosterone treatment for 24 months has no beneficial or adverse effect
      on prostate growth but causes a decrease in spinal but not hip BMD. These
      findings have important implications for the wider use of nonsteroidal pure
      androgens in older men. PRIMARY FUNDING SOURCE: BHR Pharma.

PMID- 21079218
TI  - The epidemiology of prescriptions abandoned at the pharmacy.
AB  - BACKGROUND: Picking up prescriptions is an essential but previously unstudied
      component of adherence for patients who use retail pharmacies. Understanding the
      epidemiology and correlates of prescription abandonment may have an important
      effect on health care quality. OBJECTIVE: To evaluate the rates and correlates of
      prescription abandonment. DESIGN: Cross-sectional cohort study. SETTING: One
      large retail pharmacy chain and one large pharmacy benefits manager (PBM) in the
      United States. MEASUREMENTS: Prescriptions bottled at the retail pharmacy chain
      between 1 July 2008 and 30 September 2008 by patients insured by the PBM were
      identified. Pharmacy data were used to identify medications that were bottled and
      either dispensed or returned to stock (RTS) or abandoned. Data from the PBM were
      used to identify previous or subsequent dispensing at any pharmacy. The first
      (index) prescription in a class for each patient was assigned to 1 of 3 mutually
      exclusive outcomes: filled, RTS, or RTS with fill (in the 30 days after
      abandonment, the patient purchased a prescription for a medication in the same
      medication class at any pharmacy). Outcome rates were assessed by drug class, and
      generalized estimating equations were used to assess patient, neighborhood,
      insurance, and prescription characteristics associated with abandonment. RESULTS:
      10 349 139 index prescriptions were filled by 5 249 380 patients. Overall, 3.27%
      of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with
      fill. Patients were least likely to abandon opiate prescriptions. Prescriptions
      with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40
      times and 4.68 times more likely, respectively, to be abandoned than
      prescriptions with no copayment (P < 0.001 for both comparisons). New users of
      medications had a 2.74 times greater probability of abandonment than prevalent
      users (P < 0.001), and prescriptions delivered electronically were 1.64 times
      more likely to be abandoned than those that were not electronic (P < 0.001).
      LIMITATION: The study included mainly insured patients and analyzed data
      collected during the summer months only. CONCLUSION: Although prescription
      abandonment represents a small component of medication nonadherence, the
      correlates to abandonment highlight important opportunities to intervene and
      thereby improve medication taking. PRIMARY FUNDING SOURCE: CVS Caremark.

PMID- 21079219
TI  - Informing the debate: rates of kidney transplantation in nations with presumed
      consent.
AB  - BACKGROUND: The kidney is the most common transplanted organ, accounting for
      almost all living donor transplantations and most deceased donor organ
      transplantations. The organ shortage has caused policymakers in many nations to
      debate the merits of adopting presumed consent legislation as a way to increase
      donor organ donation from deceased donors. OBJECTIVE: To compare characteristics
      and kidney transplantation rates for countries with presumed consent for deceased
      organ donation with countries with explicit consent. DESIGN: A longitudinal study
      of international kidney transplantation from 1997 to 2007. SETTING: 44 nations
      performing kidney transplantation. PATIENTS: Recipients of deceased and living
      kidney donor transplants. MEASUREMENTS: Rates of transplantation of kidneys from
      deceased and living donors. RESULTS: National characteristics, such as population
      size, proportion of the population self-identified as Catholic, per capita gross
      domestic product, health expenditures, and physician density, varied widely for
      the 22 nations with presumed consent and the 22 nations with explicit consent.
      Deceased donor kidney transplantation rates were higher in nations with presumed
      consent (median, 22.6 transplantations per million population [pmp];
      interquartile range [IQR], 9.3 to 33.8) versus nations with explicit consent
      (median, 13.9 transplantations pmp; IQR, 3.6 to 23.1). Living donor kidney
      transplantation rates were lower in nations with presumed consent (median, 2.4
      transplantations pmp; IQR, 1.7 to 4.3) versus nations with explicit consent
      (median, 5.9 transplantations pmp; IQR, 2.3 to 12.2). The findings were
      consistent when nations were classified according to per capita gross domestic
      product, health expenditures, and physician density. LIMITATION: As with any
      observational study, associations may not be causal. CONCLUSION: Nations with
      presumed consent have higher rates of deceased donor kidney transplantation than
      nations with explicit consent. Any nation deciding to adopt presumed consent
      should carefully consider and reduce any negative effect on rates of living
      donation. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and
      Lawson Health Research Institute.

PMID- 21079220
TI  - Autologous mesenchymal stem cells foster revascularization of ischemic limbs in
      systemic sclerosis: a case report.
AB  - BACKGROUND: Mesenchymal stem cells can differentiate into endothelial cells and
      participate in angiogenesis in adults. In experimental models of acute myocardial
      infarction, mesenchymal stem cells led to the recovery of cardiac function
      through the formation of a new vascular network. OBJECTIVE: To describe treatment
      with intravenous infusions of expanded autologous mesenchymal stem cells in 1
      patient with critical limb ischemia due to systemic sclerosis. DESIGN: Case
      report. SETTING: The rheumatology unit at the University of Florence, Florence,
      Italy. PATIENT: A woman, aged 34 years, with systemic sclerosis who developed
      acute gangrene of the upper and lower limbs. INTERVENTION: 3 intravenous pulses
      of expanded autologous mesenchymal stem cells. MEASUREMENTS: Angiography, skin
      histopathology, and immunohistochemistry. RESULTS: Areas of necrotic skin were
      reduced after the first mesenchymal stem-cell infusion. After the third infusion,
      angiography showed revascularization of the patient's extremities. Skin section
      analysis revealed cell clusters with tubelike structures, and angiogenic factors
      were strongly expressed. LIMITATION: Causality cannot be established by a single
      case. CONCLUSION: In patients with systemic sclerosis who have severe peripheral
      ischemia, intravenous infusion of expanded autologous mesenchymal stem cells may
      foster the recovery of the vascular network, restore blood flow, and reduce skin
      necrosis. PRIMARY FUNDING SOURCE: Fondazione Cassa di Risparmio di Pistoia e
      Pescia (partial funding).

PMID- 21079221
TI  - Streamlining ethical review.
AB  - The review system for human subjects research in the United States has been
      widely criticized in recent years for requirements that delay research without
      improving human subject protections. Any major reformulation of regulations may
      take some time to implement. However, current regulations often allow for
      streamlined ethics review that does not jeopardize-and may improve-protections
      for research participants. The authors discuss underutilized options, including
      research that need not be classified as human subjects research, categories of
      studies that can be exempt from ethical review, studies that need only undergo
      expedited review by 1 institutional review board (IRB) member, and simplifying
      reviews of multicenter research by using the IRB of 1 institution. The authors
      speculate on multiple reasons for the underuse of these mechanisms and exhort
      IRBs and researchers to take advantage of these important opportunities to
      improve the review process.

PMID- 21079222
TI  - Students' response to disaster: a lesson for health care professional schools.
AB  - The response of medical students, young physicians, and other health
      professionals to the February 2010 earthquake and tsunami in Chile provides
      important lessons about health care delivery during disasters and about the
      development of professionalism. Tertiary and secondary care of victims of these
      disasters was possible because local and national resources were available and
      field hospitals provided by Chile's armed forces and foreign countries replaced
      damaged hospitals. However, primary care of persons living on the outskirts of
      towns and in small villages and coves that were destroyed and isolated by the
      disaster required the involvement of volunteer groups that were largely composed
      of students and other young members of the health professions, all of whom were
      motivated by solidarity, compassion, and social commitment. This experience,
      similar to previous catastrophes in Chile and elsewhere, reinforces that medical
      and other health professional schools must instill in graduates an understanding
      that the privileges of being a health professional come with responsibilities to
      society. Beyond providing high-quality scientific and technological education,
      curricula in these schools should include training that enables graduates to
      meaningfully contribute in the setting of unexpected disasters and that nurtures
      a sense of responsibility to do so.

PMID- 21079224
TI  - The regional extension center program: helping physicians meaningfully use health
      information technology.
AB  - Many physicians face financial and organizational barriers that inhibit their
      adoption of electronic health record (EHR) systems. The 2009 Health Information
      Technology for Economic and Clinical Health Act included provisions to facilitate
      the transition from paper to electronic records, including Medicare and Medicaid
      incentive payments to support the adoption and meaningful use of EHR systems. It
      also created the Health Information Technology Regional Extension Center (REC)
      program to ease the barriers faced by primary care physicians and rural and
      critical-access hospitals seeking to implement EHRs. The 60 RECs will administer
      individualized assistance to primary care practices and rural and critical-access
      hospitals as they implement new EHR systems or upgrade existing ones. In
      aggregate, the RECs aim to help 100 000 primary care physicians, physician
      assistants, and nurse practitioners to effectively implement EHR systems and
      qualify for incentive payments for meaningful use. This article describes the
      rationale for the REC program and describes how the 60 RECs promote the
      meaningful use of EHR systems.

PMID- 21079223
TI  - Patient-centered discussions about prostate cancer screening: a real-world
      approach.
AB  - National guidelines recommend that primary care providers discuss the risks and
      benefits of prostate cancer screening with their patients but give little
      guidance on how to fit such a complex discussion into a busy clinic encounter.
      The authors propose a process-oriented approach (Ask-Tell-Ask) that promotes
      tailored conversations and value-based recommendations. The Ask-Tell-Ask approach
      includes diagnosing a patient's informational needs, providing targeted education
      based on those needs, and making a shared decision about testing. This time
      efficient model emphasizes the provider's role as an interactive guide rather
      than a one-way supplier of information. Although there is no way to make these
      discussions simple, this streamlined strategy can help patients and providers
      efficiently negotiate the complex and important decision of screening for
      prostate cancer.

PMID- 21079225
TI  - The evolving medical record.
AB  - Form dictates content, and the manner of recordkeeping imposed on us probably
      influences how we think about patients. At The New York Hospital, physicians
      began to maintain permanent patient case records in the early 1800s. Originally
      proposed and valued as teaching cases for medical students, these freeform
      patient records varied in quality and often reflected not just the medical care
      of the time but also the personalities of the physicians composing them. At the
      end of the 19th century, the change from retrospective to real-time recording of
      cases and the imposition of a fixed chart structure through the use of forms
      dramatically reduced the narrative dimension of the hospital course. Gradually,
      physicians found ways to circumvent these restrictions. Changes in record format,
      designed to manage increasing volumes of data, and physicians' responses to those
      changes parallel some of the contemporary threats to documentation posed by the
      electronic health record.

PMID- 21079226
TI  - Dihydrotestosterone: hormone or autocrine--paracrine signal?

PMID- 21079227
TI  - Prescription abandonment: another path to medication nonadherence.

PMID- 21079228
TI  - The clinical record: a 200-year-old 21st-century challenge.

PMID- 21079229
TI  - Masks.

PMID- 21079230
TI  - Memoirs of an obese physician.

PMID- 21079231
TI  - Extended-duration venous thromboembolism prophylaxis for medical patients.

PMID- 21079232
TI  - Extended-duration venous thromboembolism prophylaxis for medical patients.

PMID- 21079233
TI  - Extended-duration venous thromboembolism prophylaxis for medical patients.

PMID- 21079234
TI  - Creatine supplementation prevents statin-induced muscle toxicity.

PMID- 21079235
TI  - Open notes: sharing physician notes with patients.

PMID- 21079236
TI  - Open notes: sharing physician notes with patients.

PMID- 21079237
TI  - Long-term hypoxia enhances cortisol biosynthesis in near-term ovine fetal adrenal
      cortical cells.
AB  - This study was designed to determine the potential mechanism/mechanisms of
      previously observed enhanced fetal cortisol secretion following exposure to long
      term hypoxia (LTH). Pregnant ewes were maintained at high altitude (3820 m) for
      approximately the last 100 days of gestation. Between the gestation days of 138
      and 141, adrenal glands were collected from LTH and age-matched normoxic control
      fetuses. Cyclic adenosine monophosphate (cAMP), cortisol, and steroidogenic acute
      regulatory (StAR) protein were measured in response to adrenocorticotropic
      hormone (ACTH) stimulation. Cortisol responses to ACTH were also measured in the
      presence of the protein kinase (PKA) inhibitor H-89, proopiomelanocortin (POMC),
      or 22-kDa pro-ACTH. Cortisol output was higher in the LTH group compared to the
      control (P < .05), following ACTH treatment while the cAMP response was similar
      in both groups. Although PKA inhibition decreased cortisol production in both
      groups, however no differences were observed between groups. Western analysis
      revealed a significant increase in protein expression for StAR in the LTH group
      (P < .05, compared to control). Proopiomelanocortin and 22-kDa pro-ACTH did not
      alter the cortisol response to ACTH treatment. Results from the present study
      taken together with those of previous in vivo studies suggest that the enhanced
      cortisol output in the LTH group is not the result of differences in cAMP
      generation or PKA. We conclude that enhanced cortisol production in LTH adrenals
      is the result of enhanced protein expression of StAR and potential downstream
      signaling pathways.

PMID- 21079238
TI  - Expression profile of microRNAs and mRNAs in human placentas from pregnancies
      complicated by preeclampsia and preterm labor.
AB  - MicroRNAs (miRNAs) have emerged as key regulators of gene expression stability
      implicated in cell proliferation, apoptosis, and development, whereas their
      altered expression has been associated with various pathological disorders. The
      objective of this study was to assess the expression profile of miRNAs and their
      predicted target genes in placentas from patients with preeclampsia (PC) and
      preterm (PT) labor as compared to normal term (NT) pregnancies. Using microarray
      profiling of 820 miRNAs and 18,630 mRNA transcripts, the analysis indicated that
      283 of these miRNAs and 9119 mRNAs were expressed in all placentas, of which the
      relative expression of 20 miRNAs (P < .05 and >= 1.5-fold) and 120 mRNAs (P <
      .05, and 2-fold cutoff) was differentially expressed in PT and PC as compared to
      NT. The expression of miR-15b, miR-181a, miR-200C, miR-210, miR-296-3p, miR-377,
      miR-483-5p, and miR-493 and a few of their predicted target genes: matrix
      metalloproteinases (MMP-1, MMP-9), a disintegrin and metalloproteinase domains
      (ADAM-17, ADAM-30), tissue inhibitor of metalloproteinase 3 (TIMP-3); suppressor
      of cytokine signaling 1 (SOCS1); Stanniocalcin (STC2); corticotropin-releasing
      hormone (CRH), CRH-binding protein (CRHBP); and endothelin-2 (EDN2) were
      validated in these cohorts using real-time polymerase chain reaction (PCR), some
      displaying an inverse correlation with the expression of their predicted target
      genes. Functional analysis indicated that the products of these genes regulate
      cellular activities considered critical in normal placental functions and those
      affected by PC and PT labor. In conclusion, the results provide further evidence
      that placentas affected by PC and PT labor display an altered expression of a
      number of miRNAs with potential regulatory functions on the expression of
      specific target genes whose altered expression and function have been associated
      with these pregnancy complications.

PMID- 21079239
TI  - Moderate global reduction in maternal nutrition has differential stage of
      gestation specific effects on {beta}1- and {beta}2-adrenergic receptors in the
      fetal baboon liver.
AB  - Hepatic beta-adrenergic receptors (beta-ARs) play a pivotal role in mobilization
      of reserves via gluconeogenesis and glycogenolysis to supply the animal with its
      energy needs during decreased nutrient availability. Using a unique nutrient
      deprived baboon model, we have demonstrated for the first time that
      immunoreactive hepatic beta(1)- and beta(2)-AR subtypes are regionally
      distributed and localized on cells around the central lobular vein in 0.5 and 0.9
      gestation (G) fetuses of ad libitum fed control (CTR) and maternal nutrient
      restricted (MNR) mothers. Furthermore, MNR decreased fetal liver immunoreactive
      beta(1)-AR and increased immunoreactive beta(2)-AR at 0.5G. However, at 0.9G,
      immunohistochemistry and Western blot analysis revealed a decrease in beta(1)-AR
      and no change in beta(2)-AR levels. Thus, MNR in a nonhuman primate species has
      effects on hepatic beta(1)- and beta(2)-ARs that are receptor- and gestation
      stage-specific and may represent compensatory systems whose effects would
      increase glucose availability in the presence of nutrient deprivation.

PMID- 21079240
TI  - Pregnancy reduces the accuracy of the estimated glomerular filtration rate based
      on Cockroft-Gault and MDRD formulas.
AB  - OBJECTIVE: This study aims to determine the effect of pregnancy on the accuracy
      of 3 commonly used methods to estimate glomerular filtration rate ([GFR]
      creatinine clearance, the Cockroft-Gault, and modification of diet in renal
      disease [MDRD] formulas) using the inulin clearance as a reference. DESIGN:
      Longitudinal study design. SETTING: University hospital. POPULATION: A total of
      44 parous nonsmoking Caucasian women. They had a history of uneventful pregnancy
      (n = 9), preeclampsia (n = 27), and intrauterine fetal demise (n = 8). METHODS:
      Measurements were performed both in pre-pregnancy and early pregnancy (8 weeks of
      gestation) and included inulin infusion, blood pressure, and 24-hour urinary and
      serum creatinine. Agreement between methods to estimate GFR was assessed by the
      Bland and Altman method. MAIN OUTCOME MEASURES: GFR estimated by inulin and
      creatinine clearances and the Cockroft-Gault and MDRD formulas. RESULTS: During
      early pregnancy, the GFR measured by inulin increased 32% compared with the pre
      pregnant value (from 115 +/- 18 to 150 +/- 23 mL/min.1.73 m(-2)), whilst the GFR
      measured by the indirect methods only increased 20%. The observed bias and limits
      of agreements are larger in early pregnancy relative to the pre-pregnant state
      for all 3 methods. CONCLUSION: The renal hyperfiltration during pregnancy
      decreases further the accuracy of the creatinine clearance and the Cockroft-Gault
      and MDRD formulas to estimate GFR.

PMID- 21079241
TI  - Craig Thompson: the method to cancer's madness. Interview by Caitlin Sedwick.

PMID- 21079242
TI  - Platelet precursors display bipolar behavior.
AB  - In this issue, Thon et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201006102)
      demonstrate that newly released platelets exhibit bipolar behavior, shifting back
      and forth between round cells and multibodied proplatelets (Thon et al., 2010).
      The authors define this intermediate as a preplatelet and, in doing so, shed new
      insight into the terminal steps of platelet maturation.

PMID- 21079244
TI  - Plk1 negatively regulates Cep55 recruitment to the midbody to ensure orderly
      abscission.
AB  - Cytokinesis requires a membrane-remodeling and fission event termed abscission
      that occurs after chromosome segregation, cleavage furrow formation, and
      contraction have completed. In this study, we show how abscission factor
      recruitment is controlled by the Polo-like kinase 1 (Plk1). At the metaphase
      anaphase transition, Plk1 initiates cleavage furrow formation and is then
      progressively degraded during mitotic exit. During this period, Plk1
      phosphorylates the abscission factor Cep55 in trans and prevents its untimely
      recruitment to the anaphase spindle. A Plk1 phosphorylation site mutant of Cep55
      is prematurely recruited to the anaphase spindle and fails to support abscission.
      Endogenous Cep55 behaves similarly after Plk1 inhibition by the drugs BI2536 or
      GW842862. Only once Plk1 is degraded can Cep55 target to the midbody and promote
      abscission. Blocking Plk1 degradation leads to elevated levels of Plk1 at the
      midbody and the failure of Cep55 recruitment. Thus, Plk1 activity negatively
      regulates Cep55 to ensure orderly abscission factor recruitment and ensures that
      this occurs only once cell contraction has completed.

PMID- 21079243
TI  - The cell biology of polycystic kidney disease.
AB  - Polycystic kidney disease is a common genetic disorder in which fluid-filled
      cysts displace normal renal tubules. Here we focus on autosomal dominant
      polycystic kidney disease, which is attributable to mutations in the PKD1 and
      PKD2 genes and which is characterized by perturbations of renal epithelial cell
      growth control, fluid transport, and morphogenesis. The mechanisms that connect
      the underlying genetic defects to disease pathogenesis are poorly understood, but
      their exploration is shedding new light on interesting cell biological processes
      and suggesting novel therapeutic targets.

PMID- 21079245
TI  - PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity.
AB  - DNA topoisomerase IIalpha (TopoIIalpha) is an essential chromosome-associated
      enzyme with activity implicated in the resolution of tangled DNA at centromeres
      before anaphase onset. However, the regulatory mechanism of TopoIIalpha activity
      is not understood. Here, we show that PIASy-mediated small ubiquitin-like
      modifier 2/3 (SUMO2/3) modification of TopoIIalpha strongly inhibits TopoIIalpha
      decatenation activity. Using mass spectrometry and biochemical analysis, we
      demonstrate that TopoIIalpha is SUMOylated at lysine 660 (Lys660), a residue
      located in the DNA gate domain, where both DNA cleavage and religation take
      place. Remarkably, loss of SUMOylation on Lys660 eliminates SUMOylation-dependent
      inhibition of TopoIIalpha, which indicates that Lys660 SUMOylation is critical
      for PIASy-mediated inhibition of TopoIIalpha activity. Together, our findings
      provide evidence for the regulation of TopoIIalpha activity on mitotic
      chromosomes by SUMOylation. Therefore, we propose a novel mechanism for
      regulation of centromeric DNA catenation during mitosis by PIASy-mediated
      SUMOylation of TopoIIalpha.

PMID- 21079247
TI  - Phosphorylation of a membrane curvature-sensing motif switches function of the
      HOPS subunit Vps41 in membrane tethering.
AB  - Tethering factors are organelle-specific multisubunit protein complexes that
      identify, along with Rab guanosine triphosphatases, transport vesicles and
      trigger their SNARE-mediated fusion of specific transport vesicles with the
      target membranes. Little is known about how tethering factors discriminate
      between different trafficking pathways, which may converge at the same organelle.
      In this paper, we describe a phosphorylation-based switch mechanism, which allows
      the homotypic vacuole fusion protein sorting effector subunit Vps41 to operate in
      two distinct fusion events, namely endosome-vacuole and AP-3 vesicle-vacuole
      fusion. Vps41 contains an amphipathic lipid-packing sensor (ALPS) motif, which
      recognizes highly curved membranes. At endosomes, this motif is inserted into the
      lipid bilayer and masks the binding motif for the delta subunit of the AP-3
      complex, Apl5, without affecting the Vps41 function in endosome-vacuole fusion.
      At the much less curved vacuole, the ALPS motif becomes available for
      phosphorylation by the resident casein kinase Yck3. As a result, the Apl5-binding
      site is exposed and allows AP-3 vesicles to bind to Vps41, followed by specific
      fusion with the vacuolar membrane. This multifunctional tethering factor thus
      discriminates between trafficking routes by switching from a curvature-sensing to
      a coat recognition mode upon phosphorylation.

PMID- 21079249
TI  - The centennial of Man's Redemption of Man.

PMID- 21079246
TI  - Mitotic spindle disassembly occurs via distinct subprocesses driven by the
      anaphase-promoting complex, Aurora B kinase, and kinesin-8.
AB  - The mitotic spindle is a complex and dynamic structure. Although much has been
      learned about how spindles assemble and mediate chromosome segregation, how
      spindles rapidly and irreversibly disassemble during telophase is less clear. We
      used synthetic lethal screens in budding yeast to identify mutants defective in
      spindle disassembly. Real-time, live cell imaging analysis of spindle disassembly
      was performed on nine mutants defective in this process. Results of this analysis
      suggest that spindle disassembly is achieved by mechanistically distinct but
      functionally overlapping subprocesses: disengagement of the spindle halves,
      arrest of spindle elongation, and initiation of interpolar microtubule
      depolymerization. These subprocesses are largely governed by the anaphase
      promoting complex, Aurora B kinase, and kinesin-8. Combinatorial inhibition of
      these subprocesses yielded cells with hyperstable spindle remnants and dramatic
      defects in cell cycle progression, establishing that rapid spindle disassembly is
      crucial for cell proliferation.

PMID- 21079250
TI  - Thomas Linacre at the University of Padua.
AB  - The Bo (meaning 'ox' in the Venetian dialect) is the historic seat of the
      University of Padua, founded in 1222. A full-length portrait of Thomas Linacre
      stands in its prestigious Sala dei Quaranta (Hall of the Forty), so called
      because of the portraits of forty great foreign scholars of the University,
      painted by Giacomo dal Forno in 1942. Thomas Linacre came to Italy in 1485,
      following an embassy by Henry VII to the Vatican. Linacre visited Bologna,
      Florence, Rome, Venice, Vicenza and Padua, where he took his degree in medicine
      in 1496 with great distinction. During his stay in Italy he met illustrious
      humanists and physicians, including Poliziano, Hermolaus Barbarus and Aldus
      Manutius Romanus, and Nicolaus Leonicenus who further stimulated him to the
      translation of classic works by Hippocrates and Galen. In 1518 Linacre played a
      pivotal role in the foundation of the Royal College of Physicians in London
      which, as first President, he organized on the basis of Italian models. With his
      portrait, the University of Padua celebrates the life and work of an astonishing
      figure linking the Italian and English medical cultures.

PMID- 21079248
TI  - Cytoskeletal mechanics of proplatelet maturation and platelet release.
AB  - Megakaryocytes generate platelets by remodeling their cytoplasm into long
      proplatelet extensions, which serve as assembly lines for platelet production.
      Although the mechanics of proplatelet elongation have been studied, the terminal
      steps of proplatelet maturation and platelet release remain poorly understood. To
      elucidate this process, released proplatelets were isolated, and their conversion
      into individual platelets was assessed. This enabled us to (a) define and
      quantify the different stages in platelet maturation, (b) identify a new
      intermediate stage in platelet production, the preplatelet, (c) delineate the
      cytoskeletal mechanics involved in preplatelet/proplatelet interconversion, and
      (d) model proplatelet fission and platelet release. Preplatelets are anucleate
      discoid particles 2-10 um across that have the capacity to convert reversibly
      into elongated proplatelets by twisting microtubule-based forces that can be
      visualized in proplatelets expressing GFP-beta1-tubulin. The release of platelets
      from the ends of proplatelets occurs at an increasing rate in time during
      culture, as larger proplatelets undergo successive fission, and is potentiated by
      shear.

PMID- 21079251
TI  - Journal of a young man of Massachusetts.
AB  - This is a shortened account of the bitter experiences of American prisoners of
      the British during the war of 1812-14 as seen through the eyes of a young New
      Englander who kept a diary of events in various prisons on both sides of the
      Atlantic. Resentment against the delay in release from captivity at Dartmoor
      prison boiled over in April 1815 and an attempt at mass escape resulted in many
      casualties. These were admirably dealt with by Surgeon George Magrath (1775-1857)
      who had been Flag Medical Officer to Nelson in the Mediterranean. His skill and
      humanity to the American prisoners at Dartmoor earned their deep respect.

PMID- 21079252
TI  - Pioneers of immunology.

PMID- 21079253
TI  - Harvey Cushing (1869-1939) and the Hunterian laboratory: a revolution in surgical
      training.

PMID- 21079254
TI  - Victor Horsley (1857-1916) in World War I.
AB  - In 1914 Victor Horsley, 56 years old, pioneer neurosurgeon, politician and ardent
      supporter of the temperance movement volunteered for active service. After a
      brief period in France he was posted to the Middle East, initially to Egypt and
      then to Mesopotamia. There he witnessed the horrors of that campaign. His
      attempts to alleviate the appalling conditions to which the wounded were
      subjected took toll of his own health and the official cause of his death in 1916
      at Amara was heat stroke.

PMID- 21079255
TI  - James Blundell MD Edin FRCP (1790-1877): pioneer of blood transfusion.
AB  - James Blundell was an obstetrician, surgeon, physiologist and teacher. He is best
      known as the first to perform a successful human-to-human blood transfusion.
      However, he can also be accredited for significant advances in surgery and
      obstetrics. After a distinguished career at The United Hospitals of St Thomas and
      Guy's, he retired early and ended his years in relative obscurity.

PMID- 21079256
TI  - The Croonian lectures of 1917: a McGill pathologist confronts the biologists of
      England.
AB  - John George Adami (1862-1926) qualified in medicine at Manchester and in 1892 was
      appointed professor of pathology at McGill University. At the invitation of the
      Royal College of Physicians (in London) he delivered the Croonian Lectures in
      1917. He chose the title 'Adaptation and disease; the contribution of medical
      research to the study of evolution'. Adami believed that medical work had brought
      to light important facts about heredity that had not been communicated adequately
      to biological scientists. He used the lectures to describe this work, placing
      particular emphasis on his contention that acquired characters are inherited. At
      this time the medical audience at Adami's lectures would have been generally
      sympathetic to the idea that acquired characters can be inherited, though many
      leading British biologists were not sympathetic. Adami hoped that a concise
      review of the medical findings would persuade the biologists to his point of view
      or at least would be the starting point for a serious discussion of his evidence.
      However, the biologists were not persuaded and, although there were acrimonious
      personal exchanges, there was no scientific debate.

PMID- 21079257
TI  - The diary of Alice Maud Batt (1889-1969).
AB  - Alice Batt while working as a VAD nurse in 1918 during World War I was awarded
      the Albert Medal. She was also awarded the British Red Cross Society Special
      Service Cross in 1919 for 'exceptionally meritorious service' and earlier, in
      1915, had been awarded the Royal Humane Society Medal for saving a girl from
      drowning in the sea. This account is based on her own wartime diary, published
      privately by a family member, Arthur Batt.

PMID- 21079258
TI  - Jane Austen's (1775-1817) references to headache: fact and fiction.
AB  - References to headache in Jane Austen's works, both fictional and non-fictional,
      and in biographical works undertaken by Austen family members have been collated.
      These multiple references suggest that Jane Austen used headache as a narrative
      device to reflect not only physiological bodily processes but also psychological
      states, possibly based on her own experience of headache and that of female
      relations and acquaintances.

PMID- 21079259
TI  - Sir Winston Leonard Spencer Churchill (1874-1965).

PMID- 21079261
TI  - Ambroise Pare's (1510-90) birth 500 years ago.

PMID- 21079260
TI  - 'Old Spasm': William Cullen (1710-90).

PMID- 21079262
TI  - Medical heroes at Postman's Park.
AB  - An account of three doctors whose deaths while saving lives in danger are
      recorded on an unusual memorial in London.

PMID- 21079263
TI  - Mentorship in pulmonary and critical care medicine.

PMID- 21079264
TI  - Integrins, selectins, and mentors.

PMID- 21079265
TI  - Evaluation of therapeutics for RSV: an important step forward.

PMID- 21079268
TI  - Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health
      study.

PMID- 21079266
TI  - What we need to know about long-acting beta2-agonists: deja vu all over again?

PMID- 21079269
TI  - Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health
      study.

PMID- 21079270
TI  - Science and scholarship in publications.

PMID- 21079271
TI  - Surfactant therapy and intravenous zanamivir in severe respiratory failure due to
      persistent influenza A/H1N1 2009 virus infection.

PMID- 21079272
TI  - A new 3D-matching method of nonrigid and partially similar models using curve
      analysis.
AB  - The 3D-shape matching problem plays a crucial role in many applications, such as
      indexing or modeling, by example. Here, we present a novel approach to matching
      3D objects in the presence of nonrigid transformation and partially similar
      models. In this paper, we use the representation of surfaces by 3D curves
      extracted around feature points. Indeed, surfaces are represented with a
      collection of closed curves, and tools from shape analysis of curves are applied
      to analyze and to compare curves. The belief functions are used to define a
      global distance between 3D objects. The experimental results obtained on the
      TOSCA and the SHREC07 data sets show that the system performs efficiently in
      retrieving similar 3D models.

PMID- 21079273
TI  - Face recognition using nearest feature space embedding.
AB  - Face recognition algorithms often have to solve problems such as facial pose,
      illumination, and expression (PIE). To reduce the impacts, many researchers have
      been trying to find the best discriminant transformation in eigenspaces, either
      linear or nonlinear, to obtain better recognition results. Various researchers
      have also designed novel matching algorithms to reduce the PIE effects. In this
      study, a nearest feature space embedding (called NFS embedding) algorithm is
      proposed for face recognition. The distance between a point and the nearest
      feature line (NFL) or the NFS is embedded in the transformation through the
      discriminant analysis. Three factors, including class separability, neighborhood
      structure preservation, and NFS measurement, were considered to find the most
      effective and discriminating transformation in eigenspaces. The proposed method
      was evaluated by several benchmark databases and compared with several state-of
      the-art algorithms. According to the compared results, the proposed method
      outperformed the other algorithms.

PMID- 21079274
TI  - Power Watershed: A Unifying Graph-Based Optimization Framework.
AB  - In this work, we extend a common framework for graph-based image segmentation
      that includes the graph cuts, random walker, and shortest path optimization
      algorithms. Viewing an image as a weighted graph, these algorithms can be
      expressed by means of a common energy function with differing choices of a
      parameter q acting as an exponent on the differences between neighboring nodes.
      Introducing a new parameter p that fixes a power for the edge weights allows us
      to also include the optimal spanning forest algorithm for watershed in this same
      framework. We then propose a new family of segmentation algorithms that fixes p
      to produce an optimal spanning forest but varies the power q beyond the usual
      watershed algorithm, which we term the power watershed. In particular, when q=2,
      the power watershed leads to a multilabel, scale and contrast invariant, unique
      global optimum obtained in practice in quasi-linear time. Placing the watershed
      algorithm in this energy minimization framework also opens new possibilities for
      using unary terms in traditional watershed segmentation and using watershed to
      optimize more general models of use in applications beyond image segmentation. 

PMID- 21079275
TI  - Trajectory Space: A Dual Representation for Nonrigid Structure from Motion.
AB  - Existing approaches to nonrigid structure from motion assume that the
      instantaneous 3D shape of a deforming object is a linear combination of basis
      shapes. These bases are object dependent and therefore have to be estimated anew
      for each video sequence. In contrast, we propose a dual approach to describe the
      evolving 3D structure in trajectory space by a linear combination of basis
      trajectories. We describe the dual relationship between the two approaches,
      showing that they both have equal power for representing 3D structure. We further
      show that the temporal smoothness in 3D trajectories alone can be used for
      recovering nonrigid structure from a moving camera. The principal advantage of
      expressing deforming 3D structure in trajectory space is that we can define an
      object independent basis. This results in a significant reduction in unknowns and
      corresponding stability in estimation. We propose the use of the Discrete Cosine
      Transform (DCT) as the object independent basis and empirically demonstrate that
      it approaches Principal Component Analysis (PCA) for natural motions. We report
      the performance of the proposed method, quantitatively using motion capture data,
      and qualitatively on several video sequences exhibiting nonrigid motions,
      including piecewise rigid motion, partially nonrigid motion (such as a facial
      expressions), and highly nonrigid motion (such as a person walking or dancing). 

PMID- 21079276
TI  - Context-dependent kernels for object classification.
AB  - Kernels are functions designed in order to capture resemblance between data and
      they are used in a wide range of machine learning techniques, including support
      vector machines (SVMs). In their standard version, commonly used kernels such as
      the Gaussian one show reasonably good performance in many classification and
      recognition tasks in computer vision, bioinformatics, and text processing. In the
      particular task of object recognition, the main deficiency of standard kernels
      such as the convolution one resides in the lack in capturing the right geometric
      structure of objects while also being invariant. We focus in this paper on object
      recognition using a new type of kernel referred to as "context dependent."
      Objects, seen as constellations of interest points, are matched by minimizing an
      energy function mixing 1) a fidelity term which measures the quality of feature
      matching, 2) a neighborhood criterion which captures the object geometry, and 3)
      a regularization term. We will show that the fixed point of this energy is a
      context-dependent kernel which is also positive definite. Experiments conducted
      on object recognition show that when plugging our kernel into SVMs, we clearly
      outperform SVMs with context-free kernels.

PMID- 21079277
TI  - Online gesture spotting from visual hull data.
AB  - This paper presents a robust framework for online full-body gesture spotting from
      visual hull data. Using view-invariant pose features as observations, hidden
      Markov models (HMMs) are trained for gesture spotting from continuous movement
      data streams. Two major contributions of this paper are 1) view-invariant pose
      feature extraction from visual hulls, and 2) a systematic approach to
      automatically detecting and modeling specific nongesture movement patterns and
      using their HMMs for outlier rejection in gesture spotting. The experimental
      results have shown the view-invariance property of the proposed pose features for
      both training poses and new poses unseen in training, as well as the efficacy of
      using specific nongesture models for outlier rejection. Using the IXMAS gesture
      data set, the proposed framework has been extensively tested and the gesture
      spotting results are superior to those reported on the same data set obtained
      using existing state-of-the-art gesture spotting methods.

PMID- 21079278
TI  - Silhouette Segmentation in Multiple Views.
AB  - In this paper, we present a method for extracting consistent foreground regions
      when multiple views of a scene are available. We propose a framework that
      automatically identifies such regions in images under the assumption that, in
      each image, background and foreground regions present different color properties.
      To achieve this task, monocular color information is not sufficient and we
      exploit the spatial consistency constraint that several image projections of the
      same space region must satisfy. Combining the monocular color consistency
      constraint with multiview spatial constraints allows us to automatically and
      simultaneously segment the foreground and background regions in multiview images.
      In contrast to standard background subtraction methods, the proposed approach
      does not require a priori knowledge of the background nor user interaction.
      Experimental results under realistic scenarios demonstrate the effectiveness of
      the method for multiple camera set ups. 

PMID- 21079279
TI  - A Hybrid Probabilistic Model for Unified Collaborative and Content-Based Image
      Tagging.
AB  - The increasing availability of large quantities of user contributed images with
      labels has provided opportunities to develop automatic tools to tag images to
      facilitate image search and retrieval. In this paper, we present a novel hybrid
      probabilistic model (HPM) which integrates low-level image features and high
      level user provided tags to automatically tag images. For images without any
      tags, HPM predicts new tags based solely on the low-level image features. For
      images with user provided tags, HPM jointly exploits both the image features and
      the tags in a unified probabilistic framework to recommend additional tags to
      label the images. The HPM framework makes use of the tag-image association matrix
      (TIAM). However, since the number of images is usually very large and user
      provided tags are diverse, TIAM is very sparse, thus making it difficult to
      reliably estimate tag-to-tag co-occurrence probabilities. We developed a
      collaborative filtering method based on nonnegative matrix factorization (NMF)
      for tackling this data sparsity issue. Also, an L1 norm kernel method is used to
      estimate the correlations between image features and semantic concepts. The
      effectiveness of the proposed approach has been evaluated using three databases
      containing 5,000 images with 371 tags, 31,695 images with 5,587 tags, and 269,648
      images with 5,018 tags, respectively. 

PMID- 21079280
TI  - Facial deblur inference using subspace analysis for recognition of blurred faces.
AB  - This paper proposes a novel method for recognizing faces degraded by blur using
      deblurring of facial images. The main issue is how to infer a Point Spread
      Function (PSF) representing the process of blur on faces. Inferring a PSF from a
      single facial image is an ill-posed problem. Our method uses learned prior
      information derived from a training set of blurred faces to make the problem more
      tractable. We construct a feature space such that blurred faces degraded by the
      same PSF are similar to one another. We learn statistical models that represent
      prior knowledge of predefined PSF sets in this feature space. A query image of
      unknown blur is compared with each model and the closest one is selected for PSF
      inference. The query image is deblurred using the PSF corresponding to that model
      and is thus ready for recognition. Experiments on a large face database (FERET)
      artificially degraded by focus or motion blur show that our method substantially
      improves the recognition performance compared to existing methods. We also
      demonstrate improved performance on real blurred images on the FRGC 1.0 face
      database. Furthermore, we show and explain how combining the proposed facial
      deblur inference with the local phase quantization (LPQ) method can further
      enhance the performance.

PMID- 21079281
TI  - Three-dimensional culture of human mesenchymal stem cells in a polyethylene
      terephthalate matrix.
AB  - Polyethylene terephthalate (PET) was used as the scaffold material to support the
      proliferation of human mesenchymal stem cells (hMSCs). The cells were cultured
      either statically in multi-wells or in a spinner flask agitated at 80 rpm for up
      to 20 days. To optimize the cell expansion condition, effects of the initial cell
      density and basic fibroblast growth factor (bFGF) were examined. During culture,
      cell growth and metabolism were tested. After 20 days, cells were harvested and
      surface markers were identified and quantified with flow cytometry. The results
      showed that hMSCs seeded at the lowest density gave the highest expansion fold.
      hMSCs grown in porous three-dimensional (3D) matrices displayed significantly
      different characteristics in terms of their proliferation and metabolism. PET
      matrices with 3D space could sustain cell proliferation for a long time. In
      addition, a low concentration (5 ng mL(-1)) of bFGF significantly enhanced the
      expansion of hMSCs in PET. Cell attachment and distribution in PET matrices were
      studied with confocal laser microscopy and scanning electron microscopy, which
      also confirmed cell proliferation. Furthermore, most of the cells in PET matrices
      were CD29, CD44 and CD105 positive, and CD34, CD45 and CD14 negative, confirming
      that hMSCs cultured in 3D PET matrices can be expanded and maintained in their
      undifferentiated state for at least 20 days without subculturing.

PMID- 21079282
TI  - In vitro corrosion, cytotoxicity and hemocompatibility of bulk nanocrystalline
      pure iron.
AB  - Bulk nanocrystalline pure iron rods were fabricated by the equal channel angular
      pressure (ECAP) technique up to eight passes. The microstructure and grain size
      distribution, natural immersion and electrochemical corrosion in simulated body
      fluid, cellular responses and hemocompatibility were investigated in this study.
      The results indicate that nanocrystalline pure iron after severe plastic
      deformation (SPD) would sustain durable span duration and exhibit much stronger
      corrosion resistance than that of the microcrystalline pure iron. The interaction
      of different cell lines reveals that the nanocrystalline pure iron stimulates
      better proliferation of fibroblast cells and preferable promotion of
      endothelialization, while inhibits effectively the viability of vascular smooth
      muscle cells (VSMCs). The burst of red cells and adhesion of the platelets were
      also substantially suppressed on contact with the nanocrystalline pure iron in
      blood circulation. A clear size-dependent behavior from the grain nature deduced
      by the gradual refinement microstructures was given and well-behaved in vitro
      biocompatibility of nanocrystalline pure iron was concluded.

PMID- 21079283
TI  - Polycaprolactone diacrylate crosslinked biodegradable semi-interpenetrating
      networks of polyacrylamide and gelatin for controlled drug delivery.
AB  - A biodegradable semi-interpenetrating hydrogel network (semi-IPN) of
      polyacrylamide and gelatin was prepared using polycaprolactone diacrylate (mol.
      wt ~ 640) as a crosslinker. The drug-polymer interaction and IPN formation were
      investigated by attenuated total reflectance-Fourier transform infrared (ATR
      FTIR) and thermal gravimetric analysis (TGA). Scanning electron micrographs of
      lyophilized matrices revealed porous internal structure with varying pore sizes
      under equilibrium hydrated conditions, depending upon formulation composition. pH
      dependent swelling and degradation was enhanced with increasing gelatin content
      and decreasing crosslinker concentration (Cs). Compression modulus (CM) (at 20%
      strain) increased significantly from 23 +/- 1.4 to 75 +/- 2.7 kPa (p < 0.02) with
      increasing Cs (from 0.5 to 2.0 mol%), while it decreased from 162 +/- 6.4 to 23
      +/- 1.4 kPa (p < 0.05) with decreasing PAm/G ratio. Cell viability studies by MTT
      assay showed excellent cytocompatibility of matrices with fibroblast L929 cells.
      Curcumin, a hydrophobic phytochemical, was loaded by a diffusion method and its
      release profile was investigated in 4% w/v aqueous BSA solution at 75 rpm (at 37
      +/- 0.2  degrees C). Fitting of drug release data in the Korsmeyer-Peppas model
      suggested sustained release behavior up to 10 days with a combination of
      diffusion and erosion mechanism (0.5 < n < 1.0; M(t)/M(infinity) <= 0.6). The
      newly developed porous, biodegradable and elastic semi-IPNs may serve as an ideal
      matrix for controlled drug release and wound healing applications. The
      possibilities can be explored for pharmaceutical and tissue engineering
      applications.

PMID- 21079284
TI  - A novel route for the production of chitosan/poly(lactide-co-glycolide) graft
      copolymers for electrospinning.
AB  - Both chitosan and polylactide/polyglycolide have good biocompatibility and can be
      used to produce tissue engineering scaffolds for cultured cells. However the
      synthetic scaffolds lack groups that would facilitate their modification, whereas
      chitosan has extensive active amide and hydroxyl groups which would allow it to
      be subsequently modified for the attachment of peptides, proteins and drugs. Also
      chitosan is very hydrophilic, whereas PLGA is relatively hydrophobic. Accordingly
      there are many situations where it would be ideal to have a copolymer of both,
      especially one that could be electrospun to provide a versatile range of
      scaffolds for tissue engineering. Our aim was to develop a novel route of
      chitosan-g-PLGA preparation and evaluate the copolymers in terms of their
      chemical characterization, their performance on electrospinning and their ability
      to support the culture of fibroblasts as an initial biological evaluation of
      these scaffolds. Chitosan was first modified with trimethylsilyl chloride, and
      catalyzed by dimethylamino pyridine. PLGA-grafted chitosan copolymers were
      prepared by reaction with end-carboxyl PLGA (PLGA-COOH). FT-IR and(1)H-NMR
      characterized the copolymer molecular structure as being substantially different
      to that of the chitosan or PLGA on their own. Elemental analysis showed an
      average 18 pyranose unit intervals when PLGA-COOH was grafted into the chitosan
      molecular chain. Differential scanning calorimetry results showed that the
      copolymers had different thermal properties from PLGA and chitosan respectively.
      Contact angle measurements demonstrated that copolymers became more hydrophilic
      than PLGA. The chitosan-g-PLGA copolymers were electrospun to produce either nano
      or microfibers as desired. A 3D fibrous scaffold of the copolymers gave good
      fibroblast adhesion and proliferation which did not differ significantly from the
      performance of the cells on the chitosan or PLGA electrospun scaffolds. In
      summary this work presents a methodology for making a hybrid material of natural
      and synthetic polymers which can be electrospun and reacts well as a substrate
      for cell culture.

PMID- 21079285
TI  - Robust and efficient walking with spring-like legs.
AB  - The development of bipedal walking robots is inspired by human walking. A way of
      implementing walking could be performed by mimicking human leg dynamics. A
      fundamental model, representing human leg dynamics during walking and running, is
      the bipedal spring-mass model which is the basis for this paper. The aim of this
      study is the identification of leg parameters leading to a compromise between
      robustness and energy efficiency in walking. It is found that, compared to
      asymmetric walking, symmetric walking with flatter angles of attack reveals such
      a compromise. With increasing leg stiffness, energy efficiency increases
      continuously. However, robustness is the maximum at moderate leg stiffness and
      decreases slightly with increasing stiffness. Hence, an adjustable leg compliance
      would be preferred, which is adaptable to the environment. If the ground is even,
      a high leg stiffness leads to energy efficient walking. However, if external
      perturbations are expected, e.g. when the robot walks on uneven terrain, the leg
      should be softer and the angle of attack flatter. In the case of underactuated
      robots with constant physical springs, the leg stiffness should be larger than k
      = 14 in order to use the most robust gait. Soft legs, however, lack in both
      robustness and efficiency.

PMID- 21079286
TI  - Biofabrication of a three-dimensional liver micro-organ as an in vitro drug
      metabolism model.
AB  - In their normal in vivo matrix milieu, tissues assume complex well-organized
      three-dimensional architectures. Therefore, the primary aim in the tissue
      engineering design process is to fabricate an optimal analog of the in vivo
      scenario. This challenge can be addressed by applying emerging layered
      biofabrication approaches in which the precise configuration and composition of
      cells and bioactive matrix components can recapitulate the well-defined three
      dimensional biomimetic microenvironments that promote cell-cell and cell-matrix
      interactions. Furthermore, the advent of and refinements in microfabricated
      systems can present physical and chemical cues to cells in a controllable and
      reproducible fashion unmatched with conventional cultures, resulting in the
      precise construction of engineered biomimetic microenvironments on the cellular
      length scale in geometries that are readily parallelized for high throughput in
      vitro models. As such, the convergence of layered solid freeform fabrication
      (SFF) technologies along with microfabrication techniques enables the creation of
      a three-dimensional micro-organ device to serve as an in vitro platform for cell
      culture, drug screening or to elicit further biological insights, particularly
      for NASA's interest in a flight-suitable high-fidelity microscale platform to
      study drug metabolism in space and planetary environments. The proposed model in
      this paper involves the combinatorial setup of an automated syringe-based,
      layered direct cell writing bioprinting process with micro-patterning techniques
      to fabricate a microscale in vitro device housing a chamber of bioprinted three
      dimensional liver cell-encapsulated hydrogel-based tissue constructs in defined
      design patterns that biomimic the cell's natural microenvironment for enhanced
      biological functionality. In order to assess the structural formability and
      biological feasibility of such a micro-organ, reproducibly fabricated tissue
      constructs were biologically characterized for liver cell-specific function.
      Another key facet of the in vivo microenvironment that was recapitulated with the
      in vitro system included the necessary dynamic perfusion of the three-dimensional
      microscale liver analog with cells probed for their collective drug metabolic
      function and suitability as a drug metabolism model. This paper details the
      principles and methods that undergird the direct cell writing biofabrication
      process development and adaptation of microfluidic devices for the creation of a
      drug screening model, thereby establishing a novel drug metabolism study platform
      for NASA's interest to adopt a microfluidic microanalytical device with an
      embedded three-dimensional microscale liver tissue analog to assess drug
      pharmacokinetic profiles in planetary environments.

PMID- 21079287
TI  - Thermal behavior of a quantum dot nanocomposite as a color converting material
      and its application to white LED.
AB  - We present a novel nanocomposite, a mixture of a CdSe/CdS/ZnS red quantum dot
      (QD), an Sr(2)SiO(4):Eu green phosphor and silicone resin for a color converting
      material. The temperature rise and the optical characteristics of the
      nanocomposite due to the addition of the QD have been investigated in terms of QD
      content ratio and the mixing components. The experimental results suggested that
      a small addition of QDs generated a large amount of heat during light conversion
      at the wavelength of QD emission. Considering the temperature rise in a
      nanocomposite, we applied 0.2 wt% QDs on an InGaN blue LED chip. As a result, we
      could achieve a white LED device with a high color rendering index of 83.2, a
      high luminance of 65.86 lm W(-1) and a moderate temperature increase of 94 
      degrees C. The white LED converted by the newly developed QD-phosphor
      nanocomposite has great potential in future illumination.

PMID- 21079288
TI  - Low-bias conductance of single benzene molecules contacted by direct Au-C and Pt
      C bonds.
AB  - The electronic transport properties of a single benzene molecule connected to
      gold and platinum electrodes through the direct Au-C or Pt-C bond are
      investigated by using a self-consistent ab initio approach that combines the non
      equilibrium Green's function (NEGF) formalism with density functional theory
      (DFT). Our calculations show that the benzene molecule can bind to the Au(111)
      surface via direct Au-C bond at the adatom, atop and bridge sites. The largest
      zero-bias conductance is calculated for the bridge site but it is only G =
      0.37G(0) (G(0) = 2e(2)/h). In contrast benzene binds to the Pt(111) surface via
      direct Pt-C bond only at the adatom and atop sites. When the binding site is the
      adatom a stable molecular junction forms with a zero-bias conductance as large as
      1.15G(0). This originates from the efficient coupling between the extended pi
      type highest occupied molecular orbital of benzene and the conducting states of
      the Pt electrodes via the 5d(xz) atomic orbital of the adatoms. The calculated
      transmission is robust to the choice of DFT functionals, illustrating the
      potential of the Pt-C bond for constructing future molecular electronic devices.

PMID- 21079289
TI  - Preparation of a MWCNT/ZnO nanocomposite and its photocatalytic activity for the
      removal of cyanide from water using a laser.
AB  - Nano-zinc oxide (n-ZnO) was loaded onto multi-walled carbon nanotubes (MWCNTs)
      via a hydrothermal process. Here pure n-ZnO used for loading was synthesized by
      the pulsed-laser ablation technique while MWCNTs were used as received. The
      synthesized MWCNT/ZnO nanocomposites were characterized using x-ray diffraction,
      field emission scanning electron microscopy, high resolution transmission
      electron microscopy and Fourier transform infrared spectrometry. A model has been
      proposed for the structural nature of the alignment of ZnO on the surface of
      MWCNTs. The photocatalytic activity in the removal of highly toxic substances
      like cyanide (CN) was carried out in a special reactor using pulsed 355 nm UV
      generated by the third harmonic of an Nd:YAG laser. In order to understand the
      cyanide removal process, the study was carried out at different laser irradiation
      times, incident laser energies, pH of the solution and dosage of the MWCNT/ZnO
      nanocomposite. The study demonstrated that the CN removal process by MWCNT/ZnO
      composite has higher photocatalytic activity than pure n-ZnO and MWCNTs alone.
      The mechanism for the degradation using MWCNT/ZnO has been schematically
      explained. It was noticed that the oxidation process activity is affected by the
      pH of the solution, and after 20 min of UV laser irradiation, approximately 90%
      of CN had been degraded.

PMID- 21079290
TI  - A kinetic Monte Carlo analysis for the production of singularly tethered carbon
      nanotubes.
AB  - Nanoparticles that possess a single covalent tether to either another particle or
      a surface play an increasingly important role in nanotechnology, serving as a
      foundation for aggregation-based plasmonic sensors, chemically assembled
      framework structures, and scanning probe tips. Using a theoretical approach, we
      explore the reaction conditions necessary to maximize singular tethering for
      several cases of homogeneously dispersed nanoparticles, with a particular focus
      on single-walled carbon nanotubes. In the limit of particles of monodisperse size
      and equal site reactivity, the number of tethers versus the reaction conversion
      is statistically described by the well-known binomial distribution, with a
      variance that is minimal for the single tether case. However, solutions of
      nanoparticles often deviate from this ideal, and reaction events can introduce
      steric hindrance to neighboring sites or alter particle electronic properties,
      both of which can influence local reactivity. In order to study these cases we
      use the electron transfer reactions of single-walled carbon nanotubes. We find
      that the distribution in the number of monofunctional tubes, as a function of
      conversion, is largely dependent on the distribution of nanotube rate constants,
      and therefore tube chiralities, in the initial solution. As a contemporary
      example, we examine the implications of this result on the metallic-semiconductor
      separation of carbon nanotubes using electron transfer chemistry.

PMID- 21079291
TI  - Toward sub-20 nm hybrid nanofabrication by combining the molecular ruler method
      and electron beam lithography.
AB  - It is of great interest and importance to develop new nanofabrication processes
      to fabricate sub-20 nm structures with sub-2 nm resolution for next-generation
      nanoelectronic devices. A combination of electron beam lithography (EBL) and a
      molecular ruler is one of the promising methods to make these fine structures.
      Here we successfully develop a hybrid method to fabricate sub-20 nm nanogap
      devices at the desired positions with a complex structure by developing a post
      EBL process, which enabled us to avoid damaging the molecular ruler with the high
      energy electron beam, and to fully utilize the EBL resolution. It was found that
      slight etching of the Ti adhesion layer of the parent metal (Pt) by ACT935J
      solution assisted the removal of molecular rulers, resulting in improved
      enhancement in the product yield (over 70%) of nanogap devices.

PMID- 21079292
TI  - Detection of a nerve agent simulant using single-walled carbon nanotube networks:
      dimethyl-methyl-phosphonate.
AB  - Single-walled carbon nanotube (SWNT) networks were used to detect hazardous
      dimethyl-methyl-phosphonate (DMMP) gas in real time, employing two different
      metals as electrodes. Random networks of SWNTs were simply obtained by drop
      casting a SWNT-containing solution onto a surface-oxidized Si substrate. Although
      the electrical responses to DMMP at room temperature were reversible for both
      metals, the Pd-contacting SWNT network sensors exhibited a higher response and a
      shorter response time than those of the Au-contacting SWNT network sensors at the
      same DMMP concentration, due to the stronger interactions between the SWNTs and
      Pd surface atoms. In Pd-contacting SWNT network sensors, the response increased
      linearly with increasing DMMP concentration and reproducible response curves were
      obtained for DMMP levels as low as 1 ppm. These results indicate that SWNT
      networks in contact with Pd electrodes can function as good DMMP sensors at room
      temperature with scalable and fast response and excellent recovery.

PMID- 21079293
TI  - Verification of unzipping models of electromigration in gold nanocontacts by in
      situ high-resolution transmission electron microscopy.
AB  - We observed in situ the electromigration process of gold (Au) nanocontacts (NCs)
      by high-resolution transmission electron microscopy. The structural dynamics of
      the interior and surfaces of the NCs were investigated at the atomic level. In
      particular, we directly verified the evidence of the unzipping model of
      electromigration with the in situ observation of surface-edge movement. The
      fundamental parameters of NCs, i.e., conductance and tensile force, were also
      measured during in situ lattice imaging of electromigration. Atoms migrating from
      the negative electrode accumulated at the most constricted regions of the NCs,
      leading to expansion. As a result, the NCs were compressed by the two electrodes.
      We demonstrated the magnitude of the force acting on the NCs during
      electromigration. The critical voltage of electromigration was approximately 80
      mV, and the current density at the critical voltage was 60 TA m(-2). We found
      that Au nanogaps could be fabricated by applying this bias voltage to Au NCs.

PMID- 21079294
TI  - High frequency microsatellite instability has a prognostic value in endometrial
      endometrioid adenocarcinoma, but only in FIGO stage 1 cases.
AB  - OBJECTIVES: to analyze the prognostic value of microsatellite instability (MSI)
      in a population-based study of FIGO stage 1-4 endometrial endometrioid
      adenocarcinomas. STUDY DESIGN: survival analysis in 273 patients of MSI status
      and clinico-pathologic features. Using a highly sensitive pentaplex polymerase
      chain reaction to establish MSI status, cases were divided into microsatellite
      stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2-5 markers
      positive). RESULTS: after 61 months median follow-up (1-209), 34 (12.5%) of the
      patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI
      H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2-4. The 5 and
      10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85%
      and 73% in the MSI-H patients (p=0.005). CONCLUSIONS: MSI-H status assessed by
      pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1,
      but not in FIGO 2-4 endometrial endometrioid adenocarcinomas.

PMID- 21079295
TI  - Musculoskeletal disorder prevalence and risk factors in ambulance officers.
AB  - This review explores the prevalence and determinants of musculoskeletal disorders
      in ambulance officers, and the limitations of the current epidemiological
      evidence to inform the development of interventions. Relevant studies were
      selected using defined word search terms and inclusion criteria. Existing
      research shows a high annual prevalence of back, neck and shoulder
      musculoskeletal disorders in ambulance officers and emergency medical
      technicians, whilst limited research has demonstrated significant associations
      between individual, physical and psychosocial demands, and musculoskeletal
      disorders of the low-back and neck-shoulder area. However, methodological issues
      will need to be addressed in future epidemiological research in order to inform
      the development of industry specific risk assessment tools that will assist in
      identifying the complex array of interactive risk factors involved in ambulance
      work. The accurate identification of risk factors will in turn, better inform the
      establishment of multifaceted interventions to reduce the prevalence of
      musculoskeletal disorders in ambulance officers.

PMID- 21079296
TI  - Physical exercise and reduction of pain in adults with lower limb osteoarthritis:
      a systematic review.
AB  - Osteoarthritis is a degenerative joint disease. The knee and hip joints are the
      most frequently affected. Treatments fall into three main categories:
      pharmacological, non-pharmacological, and surgical. Treatments can be applied
      alone or in combination. In the last few years, within the non-pharmacological
      category have been a growing importance of physical exercise programs aimed to
      reduce pain in knee and hip joints. The purpose of this review was to summarize
      evidence for the effectiveness and structure of exercise programs on pain in
      patients with hip and knee osteoarthritis. To that end, several databases were
      searched, retrieving 33 studies that evaluated the influence of different
      exercise programs on pain. These studies were grouped according to the
      characteristics of the exercise program: land-based intervention (strength
      program, Tai Chi, aerobic program), aquatic intervention (hydrotherapy), and
      mixed exercise programs. The main conclusions drawn were: (i) despite
      recommendations for the use of exercise programs as pain therapy in patients with
      hip and knee osteoarthritis, very few randomized clinical studies were conducted;
      (ii) the structure of the exercise programs (content, duration, frequency and
      duration of the session) is very heterogeneous; (iii) on overall, exercise
      programs based on Tai Chi have better results than mixed exercise programs, but
      without clear differences.

PMID- 21079297
TI  - The relationship between serum trace elements, vitamin B12, folic acid and
      clinical parameters in patients with myofascial pain syndrome.
AB  - BACKGROUND: Myofascial pain syndrome (MPS) is characterized by myofascial trigger
      points in a palpable taut band of skeletal muscle. OBJECTIVE: We aimed to
      investigate serum trace elements, vitamin B12, folic acid levels and their
      correlations with clinical findings and functional status in patients with MPS.
      METHODS: Thirty eight patients with at least one trigger point located on
      shoulder muscles, and at least 6 months duration, were included in this study.
      The demographic data, disease duration of patients were noted. Serum copper,
      zinc, magnesium and iron levels, vitamin B12 and folic acid levels were measured.
      Visual analogue scale (VAS) was implemented to estimate daily severity of pain.
      Pain pressure threshold of subjects and control groups were assessed by using
      Fischer's tissue compliancemeter. The Turkish version of the Beck Depression
      Inventory (BDI) was administered for the presence of any depressive disorder.
      RESULTS: The mean age of patients in MPS group and control group were 33.1 and
      37.8 years respectively. Serum levels of zinc (p< 0.006) were significantly
      decreased in patients with MPS. VAS, total myalgic and BDI scores of patients
      were significantly higher than the control group (Respectively p< 0.000, p<
      0.012, p< 0.000). Association between TMS and magnesium, vitamin B12 levels was
      found statistically significant. BDI score correlated significantly with the
      serum zinc level (r:-0.548, p< 0.001) and VAS in patients with MPS (r:0.641, p<
      0.000). CONCLUSION: According to the results of this study, it was asserted that
      trace elements, vitamins may play an important role in the pathophysiology of MPS
      and psychological factors may also have additional effect.

PMID- 21079298
TI  - Evaluation of postoperative early mobilization in patients with repaired flexor
      tendons of the wrist, the spaghetti wrist.
AB  - PURPOSE: The hands and wrists are very important for performing the activities of
      daily life independently. The spaghetti wrist may involve major nerves and
      arteries, as well as the wrist and finger flexors. The purpose of this study was
      to evaluate the rehabilitation results of postoperative early mobilization in
      patients with repaired flexor tendons of the wrist. METHODS: Thirty-three
      patients with repaired flexor tendon injuries were included. Patients were
      divided into two groups due to ethylogy. Group 1 included 23 patients who
      incurred tendon injuries during fights with their family members or friends or
      due to broken glass after fighting. Two patients had cut their hands with a
      razor. The other patient had cut his hands during discussion. The Group 2
      included 10 patients. The injuries in this group were due to work and home
      accidents. RESULTS: The functional result was excellent in 46% of fingers, good
      in 22%, fair in 17%, and poor in 15% in the Group 1 patients. The results were
      excellent in 55% of fingers, good in 17%, fair in 18%, and poor in 10% in the
      Group 2 patients. CONCLUSION: Early primary repair and effective rehabilitation
      are of great importance during the postoperative period for successful results in
      the treatment of extensive volar wrist lacerations.

PMID- 21079299
TI  - Can the Fear-Avoidance Beliefs Questionnaire predict work status in people with
      work-related musculoskeletal disorders?
AB  - OBJECTIVE: To investigate the predictive validity of fear avoidance beliefs as
      assessed by the Work Subscale (FABQ-W) of the Fear Avoidance Beliefs
      Questionnaire in a sample of 117 patients with a work-related musculoskeletal
      disorder, and identify two FABQ-W cut off points that identified participants as
      high or low risk of non return to work, following an interdisciplinary
      rehabilitation program. METHODS: A retrospective analysis of patient data
      collected in conjunction with the Victorian Workcover Authority "Sprains and
      Strains" program. Sequential logistic regression analysis was used to construct a
      model of prediction from the baseline variables of age, disability (using the
      Pain Disability Index), gender and FABQ-W scores. Receiver Operator
      Characteristic (ROC) curves were used to identify FABQ-W cut off points that best
      predicted the return to work outcome. RESULTS: Age and initial FABQ-W scores
      significantly improved the predictive capabilities of the model, but gender and
      disability did not. The model explained between 13.1% and 18.2% of the
      variability in the RTW outcome. ROC curves showed maximum sensitivity was 100%
      for a score of <= 27.5, with a score of > 39.5 identified as having optimum
      specificity (81.9%). CONCLUSION: Individuals with low FABQ-W scores are likely to
      return to work, however those with high scores will not necessarily have a poor
      outcome. This study supports the limited utility of the FABQ-W score for
      screening for risk of a poor return to work outcome in patients with a work
      related musculoskeletal disorder.

PMID- 21079300
TI  - Reliability and minimal detectable change of spinal length and width measurements
      using the Flexicurve for usual standing posture in healthy young adults.
AB  - PURPOSE: The purposes of this study were to: 1) investigate the inter-rater and
      intra-rater reliability of use of the Flexicurve for measurement of spinal length
      (L), thoracic (TL) and lumbar length (LL), thoracic (TW) and lumbar width (LW),
      and 2) quantify measurement error and minimal detectable change at the 95% CI
      (MDC95) for the same measurements. METHODS: Flexicurve measurements of the
      thoracolumbar spine were recorded by two examiners in standing. Intra-class
      correlation coefficients were calculated to determine the intra- and inter-rater
      reliability. Measurement error and MDC95 were calculated to determine length and
      width measurements that would constitute real change in spinal curvature.
      RESULTS: Thoracolumbar length (L) measurements had the highest degree of intra
      rater reliability (0.93), while TL, TW, LL, LW showed moderate to good intra
      rater reliability (0.61-0.80). Inter-rater reliability for all measurements was
      moderate (0.58-0.72). Measurement error was moderate to high for TW, LL, and LW
      (15-25%), and low for L and TL (1-6%). The %MDC95 for TW, LL, and LW found in
      this study was high (>40%), but was low for L (3.5%). CONCLUSION: Thoracolumbar
      length measurement with the Flexicurve showed good intra-rater reliability, low
      measurement error, and low MDC95 and may be a useful measure in clinical
      practice.

PMID- 21079301
TI  - Psoriasis in India: prevalence and pattern.

PMID- 21079302
TI  - Golimumab and certolizumab: the two new anti-tumor necrosis factor kids on the
      block.
AB  - Anti-tumor necrosis factor (anti-TNF) agents have revolutionized treatment of
      psoriasis and many other inflammatory diseases of autoimmune origin. They have
      considerable advantages over the existing immunomodulators. Anti-TNF agents are
      designed to target a very specific component of the immune-mediated inflammatory
      cascades. Thus, they have lower risks of systemic side-effects. In a brief period
      of 10 years, a growing number of biological therapies are entering the clinical
      arena while many more biologicals remain on the horizon. With time, the long-term
      side-effects and efficacies of these individual agents will become clearer and
      help to determine which ones are the most suitable for long-term care. Golimumab
      (a human monoclonal anti-TNF-alpha antibody) and Certolizumab (a PEGylated Fab
      fragment of humanized monoclonal TNF-alpha antibody) are the two latest additions
      to the anti-TNF regimen. Here, we are providing a brief description about these
      two drugs and their uses.

PMID- 21079303
TI  - Psoriasis.

PMID- 21079304
TI  - Novel drug delivery systems in topical treatment of psoriasis: rigors and vigors.
AB  - Psoriasis is a chronic inflammatory skin disorder that may drastically impair the
      quality of life of a patient. Among the various modes of treatments for
      psoriasis, topical therapy is most commonly used in majority of patients. The
      topical formulations based on conventional excipients could serve the purpose
      only to a limited extent. With the advent of newer biocompatible and
      biodegradable materials like phospholipids, and cutting-edge drug delivery
      technologies like liposomes, solid lipid nanoparticles (SLNs), microemulsions,
      and nanoemulsions, the possibility to improve the efficacy and safety of the
      topical products has increased manifold. Improved understanding of the dermal
      delivery aspects and that of designing and developing diverse carrier systems
      have brought in further novelty in this approach. Substantial efforts and the
      consequent publications, patents and product development studies on the subject
      are the matter of interest and review of this article. However, majority of the
      work is related to the preclinical studies and demands further clinical
      assessment in psoriasis patients.

PMID- 21079306
TI  - Newer trends in the management of psoriasis at difficult to treat locations:
      scalp, palmoplantar disease and nails.
AB  - Psoriasis is a common, chronic, inflammatory disease with a wide range of
      clinical presentations. The disease severity ranges from mild to severe. Plaque
      type of psoriasis is the most common. A number of factors like previous treatment
      history and comorbid conditions influence the treatment of psoriasis in an
      individual patient. Location of the lesions is also an important consideration.
      Psoriasis localized to certain areas of the body like scalp, nails, palms and
      soles remains difficult to treat. These sites have been referred to as the
      difficult locations in literature. This article covers the management of
      psoriasis limited to these special areas.

PMID- 21079305
TI  - Psoriasis: what is new in nonbiologic systemic therapy in the era of biologics?
AB  - Psoriasis is a common debilitating disease significantly affecting the quality of
      life of the patients. Majority of the psoriasis patients have mild disease which
      can be managed by topical therapies. Around 30% of the psoriasis patients require
      systemic therapy during the course of their disease. There is a vast array of
      drugs for the treatment. Methotrexate, cyclosporine and retinoids are the most
      commonly used conventional systemic drugs. Newer studies provide insight into
      their more effective and safer use and as combination therapy with biologics. In
      recent times, many new drugs with novel mechanisms of action other than biologics
      have been tried in psoriasis. In this article, we have reviewed the current
      developments and new found role of the conventional drugs as well as the newer
      nonbiologic systemic drugs in the treatment of psoriasis.

PMID- 21079307
TI  - Management of psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory disease that can be
      progressive and may be associated with permanent joint damage and disability.
      Early identification of PsA will enable these patients with progressive disease
      to be treated early and aggressively. Due to lack of consistent diagnostic or
      classification criteria in the past, PsA was considered as uncommon. Overall it
      affects 6-10% of all psoriasis patients during the course of their disease. Both
      dermatologists and rheumatologists should be involved in the diagnosis and
      management of this disorder. Interest in PsA has greatly enhanced over the past
      several years due to many factors including a better understanding of disease
      mechanisms, improved investigational tools, better clinical trial design and
      perhaps most importantly, the availability of newer therapeutic agents. Mild
      forms of PsA can initially be treated with nonsteroidal antiinflammatory drugs
      (NSAID). In acute as well as oligo- to polyarticular joint involvement, disease
      modifying anti-rheumatic drugs (DMARD) are indicated for PsA. The biologics
      particularly tumor necrosis factor alpha (TNF-alpha) antagonists are gaining
      increasing significance as second-line therapy. Treatment choice should also take
      into consideration the extent of skin involvement.

PMID- 21079308
TI  - Narrowband ultraviolet B in the treatment of psoriasis: the journey so far!
AB  - Ever since artificial TL-01 lamps were developed, narrowband ultraviolet B
      (NBUVB) has gained giant strides in dermatology. Psoriasis is one of the common
      indications for the use of NBUVB in present day dermatology. We discuss here the
      evolution of NBUVB, its mechanism of action pertaining to psoriasis, indications
      and contraindications, dosimetry, complications of NBUVB while being used in
      patients with psoriasis, its merits and demerits in comparison with broadband UVB
      and psoralen+UVA (PUVA), and recent developments in the delivery system of NBUVB.

PMID- 21079309
TI  - Prevalence of metabolic syndrome in patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and is
      associated with an increased risk of cardiovascular atherosclerosis. Metabolic
      syndrome, a conglomerate of various clinical and biochemical parameters is a
      significant predictor of atherosclerotic disease and the associated risk for
      cardiovascular events in such patients. AIM: To investigate the prevalence of
      metabolic syndrome in patients with psoriasis. METHODS: The study was a
      prospective, hospital based case-control study involving 150 adult patients with
      chronic plaque psoriasis and 150 healthy controls. Venous samples were taken at
      the enrollment visit after the subjects had fasted overnight (at least 8 h).
      Serum cholesterol and triglycerides were measured with enzymatic procedures.
      Plasma glucose was measured using a glucose oxidase method. Metabolic syndrome
      was diagnosed by the presence of three or more criteria of the National
      Cholesterol Education Programme's Adult Panel III (ATP III). Statistical analysis
      of the data was done using statistical processing software (SPSS-17) and epi-info
      software. RESULTS: Metabolic syndrome was significantly more common in psoriatic
      patients than in controls 42(28%) vs 9(6%), odds ratio (OR) = 6.09, P<0.05.
      Psoriatic patients also had a significantly higher prevalence of
      hypertriglyceridaemia (73/150 among cases vs 24/150 among controls; P<0.05),
      arterial hypertension (74/150 among cases vs 24/150 among controls; P<0.05) and
      impaired fasting plasma glucose levels (27/150 among cases vs 04/150 among
      controls; P<0.05). Psoriatic patients with metabolic syndrome had mean disease
      duration of 13.67+/-11.87 years against 6.46+/-5.80 years in those without
      metabolic syndrome. CONCLUSION: There is a significantly higher prevalence of
      metabolic syndrome in psoriasis patients as compared to general population and so
      is the risk of having atherosclerotic adversity. While managing the psoriatic
      plaques of these patients, concerns should extend to the atherosclerotic plaques
      as well.

PMID- 21079310
TI  - Comparative efficacy of narrow-band ultraviolet B phototherapy alone and its
      combination with topical 8-methoxypsoralen in psoriasis.
AB  - BACKGROUND: Very few studies using the combination of topical 8-methoxypsoralen
      (8-MOP) and narrow-band ultraviolet B (NBUVB) have been performed, especially in
      Indian patients. A combination of oral psoralen with NBUVB has been shown to have
      a superior efficacy as compared with NBUVB alone in psoriasis. AIMS: Comparison
      of the efficacy of topical psoralen NBUVB (combination) versus NBUVB alone in
      psoriasis. METHODS: Thirty patients with plaque psoriasis were taken up for the
      study and NBUVB phototherapy was given twice weekly. The target lesions on one
      side were treated with 0.1% topical 8-MOP 15 min before the irradiation. The
      treatment period was 12 weeks or 24 exposures. RESULTS: The number of treatment
      sessions and cumulative NBUVB doses were lower in the combination therapy as
      compared with NBUVB monotherapy, although the differences were not statistically
      significant. CONCLUSION: To conclude, topical 8-MOP enhances the therapeutic
      effects of NBUVB therapy without increasing the incidence of adverse effects.

PMID- 21079311
TI  - Cutaneous manifestations of chikungunya during a recent epidemic in Calicut,
      north Kerala, south India.
AB  - BACKGROUND: There was a recent epidemic of chikungunya (CKG) in Calicut and other
      northern districts of Kerala, South India, affecting thousands of people. AIMS:
      To study the cutaneous manifestations of CKG and to have a serological and
      histopathological correlation. METHODS: A total of 162 patients (63 males and 99
      females) with cutaneous manifestations of CKG were enrolled in the study and
      serological confirmation was done with capture IgM ELISA for CKG. Skin biopsy was
      done in all representative cases. RESULTS: Cutaneous manifestations were found
      more in females. There were 23 children, the youngest being 39 days old.
      Generalized erythematous macular rash was the most common finding. Vesicles and
      bullae were also common especially in infants. Localized erythema of the nose and
      pinnae, erythema and swelling of the pre existing scars and striae and toxic
      epidermal necrolysis-like lesions sparing mucosae were the other interesting
      findings. Different types of pigmentation were observed with a striking nose
      pigmentation in a large number of patients, by looking at which even a
      retrospective diagnosis of CKG could be made. Hence we suggest this peculiar
      pigmentation may be called "chik sign". There was flare up of existing dermatoses
      like psoriasis, lichen planus and unmasking of Hansen's disease with type 1
      reaction. Serological tests were positive in 97%. Some hitherto unreported
      histopathologic findings like melanophages in the erythematous rashes were
      observed. CONCLUSION: A spectrum of cutaneous manifestations of CKG with a wide
      variety of unusual presentations with confirmed serological and histopathological
      evidence was encountered.

PMID- 21079312
TI  - Long pulsed Nd:YAG laser with inbuilt cool sapphire tip for long term hair
      reduction on type- IV and V skin: a prospective analysis of 200 patients.
AB  - BACKGROUND: Laser hair reduction has become a very popular means to get rid of
      unwanted hair. AIMS: We conducted the current study to evaluate the safety and
      efficacy of Nd: YAG laser on dark skin. We also evaluated the effect of
      increasing the gap between sessions on the long term efficacy of hair reduction
      achieved with long pulsed Nd: YAG laser. METHODS: A prospective study was
      conducted on 200 consecutive female patients who underwent laser hair reduction
      for unwanted hair over the face, at Kaya skin clinic Delhi, with long pulsed Nd:
      YAG laser, from May 2006 to May 2009. The gap between sessions was increased from
      2 nd session itself. RESULTS were evaluated 6 months after 6 sessions. Also a
      note was made of worsening of hair growth or any side effects experienced the
      patient during any of the sessions. RESULTS: A total of 200 female patients (160
      skin type IV and 40 skin type V) were followed up. Of these, 64 enrolled for
      lower face, 88 for chin or upper neck and 48 for upper lip. 6 months after 6
      sessions, more than 50% improvement was seen in 68.7% of lower face, 89.69% cases
      of chin and 59% of upper lip cases. None of the patients had any worsening.
      CONCLUSIONS: The current study shows that long pulsed Nd: YAG is a very safe and
      effective means of hair reduction in skin types IV and V. Adequate fluences and
      increasing the gap between sessions from the 2 nd session could be the key to
      achieving long term hair reduction with Nd: YAG laser. Adequate cooling and
      proper shaving are the key factors determining the safety.

PMID- 21079313
TI  - Bacillary angiomatosis with atypical clinical presentation in an immunocompetent
      patient.
AB  - Bacillary angiomatosis is a recently described infectious disease that usually
      affects immunosupressed hosts with a previous history of contact with cats. We
      report a rare case of bacillary angiomatosis in an immunocompetent 59-year-old
      woman with no history of previous exposure to cats, and atypical clinical
      features (fever and subcutaneous nodules with ulceration on the left ankle).
      Histopathology of the lesion showed extensive ulceration and reactive tumor-like
      vascular proliferation of the blood vessels with swollen endothelial cells and an
      inflammatory infiltrate including neutrophils and lymphocytes in the dermis and
      subcutis. Staining with the Warthin-Starry method demonstrated the presence of
      clustered bacilli located in the extracellular matrix adjacent to the
      proliferating endothelial cells. Diagnosis was confirmed with the detection of
      Bartonella spp. DNA in the affected skin and in bone marrow using polymerase
      chain reaction.

PMID- 21079314
TI  - Granulomatous mycosis fungoides with hypohidrosis mimicking lepromatous leprosy.
AB  - Granulomatous mycosis fungoides (GMF) is a rare type of cutaneous T cell
      lymphoma. A 38-year-old married male presented with decreased sweating all over
      the body for last 8 years, progressive redness and scaling over body for 2 years
      and multiple noduloulcerative lesions over the body for 1 year. Cutaneous
      examination revealed generalized erythema and scaling with poikilodermatous
      changes over chest and upper back along with multiple noduloulcerative lesions.
      Skin biopsy from a nodular lesion revealed dense granulomatous infiltrate of
      atypical lymphocytes with epidermotropism and sparing of appendages. Diagnosis of
      GMF was made. Computed tomographic scan of thorax, abdomen and pelvis revealed
      axillary and inguinal lymphadenopathy. Immunohistochemistry revealed leukocyte
      common antigen and CD3 positivity suggestive of T cell origin. Patient was
      started on CHOP (Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisolone)
      regimen of chemotherapy with marked improvement after three cycles of
      chemotherapy. This case had some clinical resemblance to lepromatous leprosy.

PMID- 21079315
TI  - Dramatic response of propranolol in hemangioma: report of two cases.
AB  - Hemangiomas are indolent birthmarks of vascular origin, which are known to appear
      soon after birth, proliferate for 8-18 months, and then slowly regress over the
      next 5-8 years, leaving behind normal or slightly blemished skin. In rare
      instances, hemangiomas may encroach upon and endanger vital structures with a
      mortality of up to 60%. Multiple therapeutic modalities are available for
      hemangiomas with variable results and associated with side effects. We report two
      cases of hemangioma, successfully treated with propranolol. Case 1 was a 5-month
      old female child who presented with a giant segmental hemangioma since birth. She
      was unable to open her left eye over the past 7 days. Within 48 hours of
      administering full dose of oral propranolol (2 mg/kg/day), the lesion decreased
      considerably, and the patient was able to open her eye. Case 2 was a 1-year-old
      female child who presented with hemangioma over the danger area of face. Oral
      propranolol was given for a period of 6 months with monthly follow up. Both the
      cases showed dramatic response, with more than 80% regression, without any
      relapse after stopping the treatment.

PMID- 21079316
TI  - Subcutaneous phaeohyphomycosis caused by Cladophialophora boppii.
AB  - Subcutaneous phaeohyphomycosis is an infection of the skin and subcutaneous
      tissue, caused by dematiaceous fungi. An adult male presented with a history of
      multiple reddish nodules over the face and hands. Histopathological examination
      of the skin biopsies showed a dense granulomatous infiltrate of macrophages,
      containing intracytoplasmic basophilic bodies throughout the dermis. Gomori
      methenamine-silver stained sections revealed yeast cells within macrophages.
      Multiple cultures on Sabouraud's dextrose agar grew Cladophialophora boppii. The
      patient was treated with oral itraconazole for a year and the response monitored
      with dermal ultrasound. This is the first case report of subcutaneous
      phaeohyphomycosis caused by Cl. boppii in India.

PMID- 21079317
TI  - Congenital hypertrichosis lanuginosa.

PMID- 21079318
TI  - Human papillomavirus: the silent intruder.

PMID- 21079319
TI  - Cosmeceutical testing: ethical and scientific issues.

PMID- 21079320
TI  - Pattern and clinical characteristics of patients with nail psoriasis in Sarawak
      General Hospital, Malaysia.

PMID- 21079321
TI  - Association of polymorphic light eruption and autoimmune thyroiditis.

PMID- 21079322
TI  - Factors predicting the preference of complementary and alternative systems of
      medicine in treatment of vitiligo.

PMID- 21079323
TI  - Localization of T-cell subsets in cutaneous lichen planus: an insight into
      pathogenetic mechanism.

PMID- 21079324
TI  - Prevalence of HIV-2 infection in Mumbai.

PMID- 21079325
TI  - Different faces of leukemia cutis: presenting as purpura fulminans and lupus like
      butterfly rash.

PMID- 21079326
TI  - Unusual presentation of cutaneous myiasis.

PMID- 21079327
TI  - Serpentine supravenous pigmentation. A rare vasculo-cutaneous effect induced by
      systemic 5-fluorouracil.

PMID- 21079328
TI  - Unilateral nevoid acanthosis nigricans and neurofibromatosis 1: an unusual
      association.

PMID- 21079329
TI  - The art and science of medical poster presentation.

PMID- 21079330
TI  - Multiple translucent papules on the face of a middle-aged woman.

PMID- 21079331
TI  - McCune-Albright syndrome: a case report in a male.
AB  - McCune-Albright syndrome (MAS) is a rare, heterogenous, clinical condition caused
      by a rare genetic mutation. The disorder is more common in females and is
      characterized by a triad of cutaneous, bone and endocrine abnormalities. We
      describe a male patient with MAS having multiple cafe-au-lait macules and
      deforming polyostotic fibrous dysplasia involving long bones of the limbs, skull
      and spine without any endocrine abnormality. Severe bone deformities involving
      almost all bones have not been described previously and this prompted us to
      present the current case.

PMID- 21079332
TI  - Cutaneous CD4+/CD56+ hematodermic neoplasm.
AB  - CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is
      a rare and aggressive neoplasm with a high incidence of cutaneous involvement,
      risk of leukemic dissemination and poor prognosis. The characteristic features
      are expression of the T helper inducer cell marker CD4 and the NK-cell marker
      CD56 in the absence of other T cell or NKcell specific markers. Because of the
      rarity of this disease, we describe a 48 year old woman suffering from CD4+/CD56+
      hematodermic neoplasm on her cheek without leukemic infiltration.

PMID- 21079334
TI  - Apert syndrome.

PMID- 21079333
TI  - Coexistence of onychomycosis in psoriatic nails: a descriptive study.
AB  - BACKGROUND: Psoriatic nail changes predispose to onychomycosis because it becomes
      easier for fungi to penetrate an already compromised nail plate. Moreover, some
      of the psoriatic nail changes closely resemble onychomycosis. AIM: To investigate
      cases of nail psoriasis for any evidence of onychomycosis. METHODS: Seventy-two
      patients with psoriasis were included in the study. The patients were selected
      from the psoriasis clinic and dermatology in-patient ward. Direct microscopic
      examination with 20% KOH and culture were carried out in all patients showing
      psoriatic nail changes. Histopathological examination with Periodic Acid-Schiff
      (PAS) stain was done in cases negative by KOH examination and culture. RESULTS:
      Nail changes were seen in 66.66% (48/72) of psoriasis patients. The most common
      fingernail changes observed were pitting, onycholysis and subungual
      hyperkeratosis, and the most common toenail changes were onycholysis and
      subungual hyperkeratosis. Nail changes were significantly more common in males.
      The duration of skin lesions of psoriasis and Psoriasis Area Severity Index
      scores were significantly higher in patients with nail changes. Out of 48
      patients with psoriatic nail change, 23 (47.91%) had investigative evidence of
      onychomycosis. The fungal isolates on culture were non-dermatophytic molds in
      nine patients (18.75%) and yeast like fungi also in nine patients (18.75%).
      CONCLUSION: Coexistent onychomycosis in psoriatic nails does occur.

PMID- 21079335
TI  - Linear perforating lesions in dystrophic epidermolysis bullosa: is it Koebner's
      phenomenon?

PMID- 21079336
TI  - Effect of mometasone 0.1% and salicylic acid 5% versus mometasone 0.1% on
      histamine wheal suppression.

PMID- 21079338
TI  - Confluent and reticulated papillomatosis: successful treatment with minocycline.

PMID- 21079337
TI  - Fetal varicella syndrome.
AB  - Fetal varicella syndrome is a rare condition of the newborn, presenting with
      cutaneous scars, limb defects and ocular and central nervous system
      abnormalities. It is due to varicella or zoster developing in the fetus following
      maternal varicella infection during early pregnancy. We are reporting one such
      patient who presented with a linear, depressed, erythematous scar over the left
      forearm and axillary fold, with a history of maternal chicken pox during the
      first trimester of pregnancy.

PMID- 21079339
TI  - Chlorination mechanism of carbon during dioxin formation using Cl-K near-edge X
      ray-absorption fine structure.
AB  - Many environmental organic chemicals have chloride in their structure. Thus,
      researching the chlorination mechanism of carbon is of interest. Dioxins are
      typically concentrated in fly ash collected from the post-combustion zone during
      the operation of municipal solid waste incinerators. In this study, we report the
      application of Cl-K near-edge X-ray-absorption fine structure (NEXAFS) in
      determining the chlorination mechanism of carbon in fly ash. The separation of a
      chloride-carbon (C-Cl) bond was readily recognizable as a peak in the Cl-K NEXAFS
      spectrum. Chlorination effects could be estimated using Cl K-edge NEXAFS with no
      dependence on metal species. Analysis of Cl K-edge NEXAFS spectra showed the
      reduction of copper(II) chloride at 300 degrees C and oxidation of iron(III)
      chloride at 400 degrees C in connection with the chlorination of carbon.

PMID- 21079340
TI  - Novel fire investigation technique using needle extraction in gas chromatography.
AB  - A novel fire investigation technique using a needle extraction device was
      studied. Using a polymer particle-packed needle device, air samples containing
      volatile organic compounds (VOCs) generated from fire accelerants, gasoline and
      kerosene were extracted effectively, and subsequent gas chromatographic (GC)
      analyses were successfully carried out. Carpet and wood samples were spiked with
      gasoline and kerosene, followed by monitoring of the time-variation profiles of
      emitted VOCs up to 48 h. The fire accelerants were also measured for combusted
      carpet and wood samples, and the applicability of the proposed method to fire
      investigations was confirmed. Even at 48 h after spiking, groups of
      characteristic compounds were clearly observed in the air environments near the
      combusted sample. This method was further applied to the determination of VOCs in
      simulated fires, strongly suggesting the applicability of the developed method to
      real fire investigations.

PMID- 21079341
TI  - Simultaneous determination of isoniazid, pyrazinamide, rifampicin and
      acetylisoniazid in human plasma by high-performance liquid chromatography.
AB  - A sensitive and accurate high-performance liquid-chromatography method was
      developed and validated for the simultaneous determination of pyrazinamide (PZA),
      isoniazid (INH), rifampicin (RFP) and acetylisoniazid (AcINH) in human plasma.
      Separation was performed on a Max-RP C(12) column using gradient elution and a
      flow-rate program. The mobile phase was methanol-acetonitrile-buffer (20 mM of
      heptanesulfonic acid sodium, pH 2.5) with a ratio of 10:8:82 (v/v/v) at the
      initial phase. All calibration curves had good linearity (r(2) > 0.99) between
      the test ranges. The intra- and inter-day precision was less than 8.8% in good
      accuracy (<15%). The limit of detection with a signal-to-noise (S/N) of 3 was
      0.014, 0.009, 0.023 and 0.054 ug mL(-1) for PZA, AcINH, INH and RFP,
      respectively. The method was selective, sensitive and reliable, and is a good
      alternative for routine therapeutic drug monitoring of the four compounds during
      the treatment of tuberculosis patients.

PMID- 21079342
TI  - Experimental and simulation research of the separation of amino acids on micro
      free-flow electrophoresis chip with voltage applied in two-dimensions.
AB  - A micro-free flow electrophoresis (uFFE) analytical system with voltage applied
      in two dimensions was proposed. Both fluid transport and separation were driven
      electrokinetically. The Alpha-Imager was applied as an in-situ detector, which
      could observe, scan and analyze the photometric state of the whole separating
      area. The mass-transfer process and the range of voltages applied on the chip
      were simulated and calculated by MATLAB software. Then, the chip design with a
      separating chamber, which was 12 mm in length, 5 mm in width and 20 um in depth,
      was presented. Under the CZE-CZE mode, the operational conditions, such as the
      EOF, the pH of the buffer and the ratio of the voltage applied in two dimensions,
      were optimized. Mixed amino acids, including FITC-labeled L-lysine, FITC-labeled
      L-phenylalanine and FITC-labeled L-aspartic, were successfully separated on the
      chip when the borate buffer contained 3% glycerol, with pH as 11 and the ratio of
      field strength in two-dimension was 1:7. The resolution could achieve 2.1 and
      1.9, respectively.

PMID- 21079343
TI  - Monitoring the on-line concentration and separation of gold nanoparticles using
      the reversed electrode polarity stacking mode and micellar electrokinetic
      chromatography.
AB  - In this study, I separated gold nanoparticles (Au NPs) using the reversed
      electrode polarity stacking mode (REPSM) of a capillary electrophoresis system
      for on-line enhancement prior to performing micellar electrokinetic
      chromatography (MEKC). In the first part of this paper, I discuss the effects of
      several new and important parameters, the nature of the added salt, the pH of the
      sample matrix, and the size of the injection buffer plug that appears after
      introducing the samples, on the systems' on-line concentration and separation
      performance for a variety of sample compositions. In the second part of this
      paper, I describe my use of the optimized conditions to monitor the migration of
      the Au NPs during the concentration and separation processes. The results of
      these studies suggest that combining REPSM with MEKC is a very good strategy for
      the on-line concentration and separation of Au NPs at trace concentrations.

PMID- 21079344
TI  - Effect of urea on the ion-association capillary electrophoresis separation of the
      anionic metal complexes using hydrophobic tetraalkylammonium as ion-association
      agent.
AB  - The effect of urea as an electrophoretic buffer solution modifier on the ion
      association (IA) capillary electrophoresis (CE) separation of four anionic metal
      complexes of Al(III), Co(III), Cr(III), and Fe(III) with 2,2'
      dihydroxyazobenezene-5,5'-disulfonate (DHABS) using a hydrophobic ion-association
      agent, tetrapentylammonium bromide, was studied. The mutual separation of the
      four anionic metal-DHABS complexes was not achieved without the addition of urea
      in the electrophoretic buffer solution. However, the addition of 1.5 M urea in
      the electrophoretic buffer solution brought about a complete separation of the
      four metal complexes. The ion-association constants between all metal-DHABS
      complexes and tetrapentylammonium in an aqueous urea solution were smaller than
      those in a neat aqueous solution. This indicates the hydrophobic interaction
      contributing to the ion-association between analytes and ion-association agent
      during IA-CE separation processes can be controlled with the addition of urea to
      the electrophoretic buffer solution. Another advantage of adding urea was a
      substantial enhancement of separation efficiency with a reduction of the half
      bandwidth of the peaks. Also, a reduction of the electrophoretic mobility of the
      electroosmotic flow when urea was added was much less than when organic solvents
      were used.

PMID- 21079345
TI  - On-line enrichment and measurement of four halogenated phenols in water samples
      using pressure-assisted electrokinetic injection-tandem mass spectrometry.
AB  - A rapid and sensitive method using pressure-assisted electrokinetic injection
      (PAEKI) as the on-line sample enrichment technique and electrospray-tandem mass
      spectrometry as the monitor has been developed for the determination of four
      halogenated phenols, 2,4,6-trichlorophenol, 2,4-dichlorophenol, 2,3,4,6
      tetrachlorophenol and tetrabromobisphenol A, in water samples. In 8-min of
      injection, the four halogenated phenols in water samples were enriched up to
      several thousand times. With the aid of a solid-phase extraction clean-up
      procedure, the method achieved a detection limit in the range of 7.4 to 37.1 ng
      L(-1) for the four phenols by multiple reaction monitoring in a negative mode.
      The overall recoveries for all four halogenated phenols in water samples were in
      the range of 68 to 114%. The good method repeatability has been demonstrated by
      the relative standard deviations (RSDs) of less than 10% for water samples spiked
      with standard mixtures. The four target phenols in all the water samples were
      below the detection limits.

PMID- 21079346
TI  - Application and equivalence assessment for determining ethamsylate by using
      potassium ferricyanide as spectroscopic probe reagent.
AB  - In this paper, a novel method has been established to determine ethamsylate using
      potassium ferricyanide as a spectroscopic probe reagent. It has been demonstrated
      that Fe(III) is reduced to Fe(II) by ethamsylate, and that the formed Fe(II)
      reacts with potassium ferricyanide to form soluble prussian blue
      (KFe(III)[Fe(II)(CN)(6)]). Beer's law is obeyed in the range of 0.16 - 24.00 ug
      mL(-1) with the molar absorption coefficient of 2.1 * 10(4) L mol(-1) cm(-1). The
      detection limit (3 sigma/k) is 0.11 ug mL(-1). This method has been successfully
      applied to determine ethamsylate in pharmaceutical and serum samples with
      satisfactory results, and presented quite satisfactory credibility during method
      equivalence assessment.

PMID- 21079347
TI  - Visual detection of Hg2+ with high selectivity using thymine modified gold
      nanoparticles.
AB  - Here, we describe a colorimetric sensor for detecting Hg(2+) in aqueous media,
      which is simply constructed by the self-assembly of thymine acetamidoethanethiol
      (T-SH) on gold nanoparticles (AuNPs). Based on the specific interaction of Hg(2+)
      with two thymines (T), the T-SH modified AuNPs can be induced to aggregate
      through the formation of a stable T-Hg-T complex in the presence of Hg(2+),
      resulting in a color change from red to blue-gray. As low as 0.5 uM of Hg(2+) can
      be easily monitored by the naked eye using this sensor. Other metal ions,
      including Zn(2+), Cd(2+), Pb(2+), Ni(2+), Cu(2+), Co(2+), Mn(2+), Ba(2+), Fe(2+),
      Ca(2+), Mg(2+), Al(3+), and Fe(3+), could not cause any response, even at
      concentrations 100-fold higher than Hg(2+). The high selectivity, high stability
      and easy operation enable this sensor suitable for the rapid on-site detection of
      Hg(2+) pollution.

PMID- 21079348
TI  - Simultaneous voltammetric determination of nitrate and nitrite ions using a
      copper electrode pretreated by dissolution/redeposition.
AB  - Nitrate and nitrite ions were found to be successfully electroreduced at an in
      situ electrochemically pretreated copper electrode in acidic media, and their
      reduction peaks of a cyclic voltammogram were found at two distinct electrode
      potentials. Cyclic voltammetric experiments revealed a highly sensitive behavior
      of the pretreated copper electrode upon the electroreduction of nitrate and
      nitrite ions, and showed that a simultaneous voltammetric determination of the
      ions was achievable. Differential pulse voltammetry (DPV) was applied to the
      simultaneous determination. As a result, the detection limits were 0.26 and 0.17
      umol dm(-3) for nitrate and nitrite ions, respectively. Simultaneous
      determinations for real samples (river water) were carried out by DPV at the
      pretreated copper electrode and spectrophotometry (the Griess method). The
      determination values obtained by both methods were in a good agreement with each
      other.

PMID- 21079350
TI  - Several factors influencing the stability of extracted species in synergistic
      extraction of lanthanide(III) with pivaloyltrifluoroacetone and 2,2'-bipyridyl.
AB  - The stability constants and the hydration number of a complex between
      tris(pivaloyltrifluoroacetonato)lanthanide(III) (LnA(3)) and 2,2'-bipyridyl (B),
      LnA(3)B, and the complexation heat were determined across the Ln series by a
      solvent-extraction technique, Karl Fischer coulometry, and calorimetry,
      successively. The number of water molecules released from LnA(3) upon the
      complexation with B as well as the values of the stability constant increased
      along with increasing Ln atomic number to around Dy(III); via a maximum, it
      decreased. It is concluded that the largest stability constant of the complex of
      Ho(III) or this vicinity is derived from the strongest bond energy, due to the
      fitness between LnA(3) and B. This conclusion was supported by the trend of the
      variation of the entropy change as well as that of the hydration number across
      the Ln series.

PMID- 21079349
TI  - Direct electrochemistry of hemoglobin immobilized on hydrophilic ionic liquid
      chitosan-ZrO2 nanoparticles composite film with carbon ionic liquid electrode as
      the platform.
AB  - A stable composite film composed of 1-butyl-3-methyl-imidazolium
      tetrafluoroborate, chitosan, zirconia nanoparticles and the hemoglobin (Hb) was
      cast on the surface of an ionic liquid of an N-butylpyridinium
      hexafluorophosphate modified carbon paste electrode to fabricate a modified
      electrode. Scanning electron microscopy images of the modified electrode
      indicated that there was a dendritic structure on the modified electrode, and UV
      Vis and FT-IR spectra showed that Hb in the composite film retained its native
      structure. Voltammetric experiments at the modified electrode showed that, in a
      pH 7.0 phosphate buffer solution, a pair of well-defined and quasi-reversible
      redox voltammetric peaks was obtained with the formal potential located at -0.216
      V. The electrochemical parameters of Hb in the composite film were further
      carefully calculated: the electron-transfer rate constant was 0.52 s(-1) and the
      charge transfer coefficient was 0.34. The catalytic reduction peak current had a
      linear relationship with the concentration of trichloroacetic acid (TCA) in the
      range from 0.2 to 10.3 mmol/L with a detection limit of 66.7 umol/L. Therefore,
      the composite film as a novel matrix opened up a possibility for further study on
      the design of enzymatic biosensors with potential applications.

PMID- 21079351
TI  - Kinetic analysis of the lactate-dehydrogenase-coupled reaction process and
      measurement of alanine transaminase by an integration strategy.
AB  - Kinetic analyses of lactate-dehydrogenase (LD)-coupled alanine transaminase (ALT)
      reaction processes were investigated for measuring ALT by an integration
      strategy. For measuring ALT by a kinetic analysis of an LD-coupled ALT reaction
      curve, candidate reaction curves were calculated via iterative numerical
      integration of the differential velocity equations to execute a weighted
      nonlinear-least-square-fitting. To realize the integration strategy, the
      conventional initial-velocity method was used if the ALT activities were below 25
      U/L; otherwise, kinetic analyses of the reaction curves were employed. Of the
      reaction curves recorded at 10-s intervals, kinetic analyses gave ALT activities
      resistant to deviations in the LD kinetic parameters. The integration strategy
      yielded a higher value of the lower limit, but an upper limit of over 100 U/L by
      simulations and over 75 U/L with purified ALT. Also, its intra-run relative
      standard deviations were below 9% for 0.50 U/L ALT and below 5% for final 1 to 65
      U/L ALT. The integration strategy gave consistent ALT activities in clinical
      sera. Hence, this new approach for kinetic analyses of ALT reaction processes and
      the integration strategy were effective to measure ALT.

PMID- 21079352
TI  - Reducing acyl migration during purification of 2-arachidonoylglycerol from
      biological samples before gas chromatography mass spectrometry analysis.
AB  - Endocannabinoid 2-arachidonoylglycerol (2-AG) regulates several important
      physiological processes in the brain. 2-AG is commonly quantified by gas
      chromatography mass spectrometry after an initial purification step. The most
      precise and rapid purification utilizes C(18) solid-phase extraction, but
      quantification problems can arise with acyl migration from 2-AG to 1
      arachidonoylglycerol. We found that extraction with methanol promoted this
      migration, but acetone and diethyl ether (Et(2)O) did not. Acetone and Et(2)O
      were used to develop a purification method for the direct determination of 2-AG.

PMID- 21079353
TI  - Stability of a Ag/AgCl reference electrode equipped with an ionic liquid salt
      bridge composed of 1-methyl-3-octylimidazolium bis(trifluoromethanesulfonyl)
      amide in potentiometry of pH standard buffers.
AB  - The stability of a Ag/AgCl reference electrode equipped with a gelled ionic
      liquid, 1-methyl-3-octylimidazolium bis(trifluoromethanesulfonyl)amide
      (C(8)mimC(1)C(1)N), as a salt bridge, was examined in the potentiometry of pH
      standard solutions. The variation in the liquid junction potential (LJP) of the
      ionic liquid (IL)-type reference electrode, measured with respect to a double
      junction-type KCl reference electrode, was within 1 mV when one standard solution
      was replaced by another, except for the phthalate standard. The time course of
      the potential of the IL-type reference electrode showed a standard deviation of
      +/-0.3 mV in all buffer solutions. The reproducible deviation of the potential of
      the IL-type reference electrode in the phthalate pH standard amounted to 5 mV.
      The deviation is due to the partition of the hydrogen phthalate in the
      C(8)mimC(1)C(1)N, influencing the phase boundary potential (PBP) across the
      interface between C(8)mimC(1)C(1)N and the phthalate standard. If a citrate
      standard is used instead of the phthalate buffer, the IL salt bridge works
      satisfactorily as a salt bridge for a reference electrode suitable for
      potentiometoric pH measurements.

PMID- 21079355
TI  - Stimulation of autophagy in the liver by lipopolysaccharide-induced systemic
      inflammation in a rat model of diabetes mellitus.
AB  - The dysregulated metabolism associated with diabetes mellitus (DM) impairs
      membrane trafficking events in the liver, including the process of autophagy,
      which is an essential ongoing cellular process that is highly regulated by
      nutrients, endocrine factors, and signaling pathways. High-mobility group box 1
      (HMGB1) is a nuclear protein with a known role in systemic inflammation and the
      related various organ injuries. However, its relationship to autophagy is not
      well understood. The aim of this study was to investigate the effects of
      inflammation injury on autophagy in the liver in a rat model of DM. DM was
      induced in animals with streptozotocin, followed four weeks later by induction of
      inflammation by LPS injection. At 12 h after LPS administration, autophagy was
      assessed by immunohistochemistry and Western blot analysis of microtubule
      associated protein light chain 3 (LC3)-II, as well as transmission electron
      microscopy. Expression of HMGB1 was also examined by immunohistochemistry and
      Western blot analysis. Western blot analysis of liver tissue revealed that levels
      of LC3-II and HMGB1 protein increased in DM rats subjected to LPS-induced
      inflammation compared with non-DM rats. Autophagy was particularly enhanced in DM
      rats. Thus, autophagy might be related to progression to organ injury in patients
      with DM, and inflammation in these patients might be associated with over
      induction of autophagy and increased HMGB1 expression.

PMID- 21079356
TI  - Effects of alfacalcidol on muscle strength, muscle fatigue, and bone mineral
      density in normal and ovariectomized rats.
AB  - Vitamin D affects not only bone but also muscle to prevent falls and osteoporotic
      fractures. However, these effects on muscle and the mechanisms of fall prevention
      are still unclear. The purpose of this study was to investigate the effects of
      alfacalcidol [1alpha(OH)D(3)] on muscle strength, muscle fatigue, and bone
      mineral density (BMD) in ovariectomized rats. Seven-month-old female Wistar rats
      were orally administered 1alpha(OH)D(3) or its vehicle everyday for 4 weeks after
      ovariectomy (OVX) or sham operation. Calf muscle strength and fatigue were
      evaluated by electrical stimulation of the sciatic nerve under general
      anesthesia. 1alpha(OH)D(3) administration significantly increased the maximum
      muscle strength in the sham-operated (P < 0.01) and the OVX (P < 0.01) groups
      compared to their respective control groups. However, 1alpha(OH)D(3)
      administration did not significantly affect muscle fatigue in these groups. The
      BMD of the femur in the 1alpha(OH)D(3)-treated OVX group was significantly higher
      than that in the vehicle-treated OVX group (P = 0.04). These results suggested
      that 1alpha(OH)D(3) increases muscle strength but does not affect muscle fatigue
      in this rat model. The effectiveness of activated vitamin D in preventing bone
      fractures may be partly owing to its effect on muscle strength in addition to its
      known effect on bone metabolism.

PMID- 21079357
TI  - Dexamethasone-induced plasminogen activator inhibitor-1 expression in human
      primary bone marrow adipocytes.
AB  - Several studies have demonstrated the association of plasminogen activator
      inhibitor-1 (PAI-1) with osteonecrosis, but the underlying mechanism of
      osteonecrosis and its relationship with local PAI-1 is not clear. The objective
      of this study was to evaluate PAI-1 production by primary human bone marrow
      adipocytes and the effects of glucocorticoid administration. Bone marrow was
      obtained from 25 individuals during prosthetic insertion. Mature adipocytes were
      cultured for 24 h with or without dexamethasone. PAI-1, adiponectin, tumor
      necrosing factor-alpha (TNFalpha) expression were measured by latex photometric
      immunoassay or RT-PCR. Adiponectin, TNFalpha and PAI-1 were detected in all
      culture media. PAI-1 expression was significantly increased by treatment with 10(
      6) mol/L dexamethasone up to 24 h in protein and mRNA levels, while the levels of
      other adipokines did not change by dexamethasone. These results suggest that bone
      marrow adipocytes may play important roles for the development of glucocorticoid
      induced osteonecrotic diseases by enhancing PAI-1 expression.

PMID- 21079358
TI  - Changes in neuropeptide Y gene expression in the spinal cord of chronic
      constrictive injury model rats after electroconvulsive stimulation.
AB  - Some reports have shown that electroconvulsive shock therapy (ECT) is effective
      for treating refractory neuropathic pain. However, its mechanism of action
      remains unknown. We have previously shown that electroconvulsive shock (ECS)
      improved thermal hypersensitivity in chronic constrictive injury (CCI) model rats
      and simultaneously elevated the neuropeptide Y (NPY) expression in the brain of
      these rats. In this study, we examined changes in the expression of NPY in the
      spinal cord of a CCI model. The rat model of CCI was established by ligating the
      left sciatic nerve. ECS was administered to the rats once daily for six days on
      days 7-12 after the operation using an electrical stimulator. RT-PCR was used to
      measure NPY mRNA expression in both the right and left L5 dorsal spinal cords on
      the 14th day after the operation. NPY gene expression was decreased in the dorsal
      spinal cords after ECS; however, no differences in NPY expression were observed
      between the right and left side of dorsal spinal cords, suggesting that the
      effect of changes in NPY expression after ECS on the improvement of neuropathic
      pain is not directly related to the spinal cord, but mainly to the upper central
      nerves.

PMID- 21079359
TI  - Thiol-oxidation reduces the release of amylase induced by beta-adrenergic
      receptor activation in rat parotid acinar cells.
AB  - In parotid acinar cells, the activation of beta-adrenergic receptors induces the
      accumulation of intracellular cAMP, and consequently provokes the exocytotic
      release of amylase, a digestive enzyme. The cellular redox status plays a pivotal
      role in regulating various cellular functions. Cellular redox imbalance caused by
      the oxidation of cellular antioxidants, as a result of oxidative stress, induces
      significant biological damage. In this study, we examined the effects of diamide,
      a thiol-oxidizing reagent, on amylase release by rat parotid acinar cells. In
      cells treated with diamide, the formation of cAMP and the release of amylase
      induced by the beta-agonist isoproterenol (IPR) were partially reduced. The
      inhibitory effect of diamide on the IPR-induced release of amylase could be
      abrogated by reduced glutathione or dithiothreitol. Diamide had no effect on the
      amylase release induced by forskolin, an adenylate cyclase activator, or by
      mastoparan, a heterotrimeric GTPbinding protein activator. In cells treated with
      diamide, the binding affinity for [(3)H]DHA, but not the number of binding sites,
      was reduced. These results suggest that beta-adrenergic receptor function is
      reduced by thiol-oxidation, which inhibits amylase secretion by parotid acinar
      cells.

PMID- 21079360
TI  - Different distribution of Cav3.2 and Cav3.1 transcripts encoding T-type Ca(2+)
      channels in the embryonic heart of mice.
AB  - We investigated the distribution of T-type Ca(2+) channel mRNAs in the mouse
      embryonic heart. Cav3.2, but not Cav3.1, was expressed in the E8.5 embryonic
      heart along with cardiac progenitor markers (Nkx2.5, Tbx5, Isl-1) and contractile
      proteins (alpha and beta MHC). In the E10.5 heart, the distribution of Cav3.1
      mRNA was confirmed in the AV-canal and overlapped with that of MinK or Tbx2.
      Cav3.2 mRNA was observed not only in the AV-canal but also in the outflow tract,
      along with MinK and Isl-1, indicating the expression of Cav3.2 in the secondary
      heart field. Thus, Cav3.2 may contribute to the development of the outflow tract
      from the secondary heart field in the embryonic heart, whereas Cav3.1 may be
      involved in the development of the cardiac conduction-system together with
      Cav3.2.

PMID- 21079361
TI  - Immunolocalization of DMP1 and sclerostin in the epiphyseal trabecule and
      diaphyseal cortical bone of osteoprotegerin deficient mice.
AB  - In order to define the osteocytic function in accelerated bone remodeling, we
      examined the distribution of the osteocytic lacunar-canalicular system (OLCS) and
      osteocyte-secreting molecules--dentin matrix protein (DMP) 1 and sclerostin--in
      the epiphyses and cortical bones of osteoprotegerin deficient (OPG(-/-)) mice.
      Silver impregnation visualized a well-arranged OLCS in the wild-type epiphyses
      and cortical bone, whereas OPG(-/-) mice had an irregular OLCS in the epiphyses,
      but well-arranged canaliculi in the cortical bone. DMP1-positive osteocytes were
      evenly distributed throughout the wild-type epiphyses and cortical bone, as well
      as the OPG(-/-) cortical bone. However, OPG(-/-) epiphyses revealed weak DMP1
      immunoreactivity. Thus, osteocytes appear to synthesize more DMP1 as the OLCS
      becomes regular. In contrast, sclerostin-immunoreactivity was significantly
      diminished in the OPG(-/-) epiphyses and cortical bone. In OPG(-/-) epiphyses and
      cortical bone, triple staining demonstrated few sclerostin-positive osteocytes in
      the periphery of a thick cell layer of alkaline phosphatase-positive osteoblasts
      and many tartrate resistant acid phosphatase-positive osteoclasts. Summarizing,
      the regular distribution of OLCS may affect DMP1 synthesis, while the cellular
      activities of osteoclasts and osteoblasts rather than the regularity of OLCS may
      ultimately influence sclerostin synthesis.

PMID- 21079362
TI  - Immunohistochemical analysis of periodontal reattachment on denuded root dentin
      after periodontal surgery.
AB  - This study evaluates the effects of three kinds of periodontal surgery using
      statistical analyses of histological and immunohistochemical indices. Dehiscence
      defects were made on roots of maxillary teeth in monkeys. Surgically exposed
      roots were untreated, etched with EDTA, or treated with Emdogain(r) after EDTA
      etching. Paraffin sections were stained with hematoxylin and eosin or
      immunostained for bone sialoprotein (BSP) or osteopontin (OPN) and analysed using
      several indices. The relative length of regenerated cementum and of BSP/OPN
      immunoreactive lines on dentin defect showed no differences among the three
      groups. Regenerated cementum area was larger in the etching-Emdogain group than
      in the etching group.The attached regenerated cementum in the untreated group was
      shorter than in the etching groups. Thickness of immunolabeling on detached
      cementum was larger than that on attached cementum in all of the groups. These
      findings suggest that etching reinforces the attachment of regenerated cementum,
      and that BSP and OPN are associated with the attachment, where they exercise
      strong adhesion within a certain level of thickness.

PMID- 21079363
TI  - [GPR119 agonists, a novel approach for the treatment of type 2 diabetes].

PMID- 21079364
TI  - [Bile acids and their pathophysiological role in metabolic disorders].

PMID- 21079365
TI  - [A potent and selective neuropeptide Y Y5-receptor antagonist, S-2367, as an anti
      obesity agent].

PMID- 21079366
TI  - [The current state of the drugs for the treatment of peripheral neuropathy
      induced by anticancer drugs].

PMID- 21079367
TI  - [FcRn, a critical regulator of antibody pharmacokinetics].

PMID- 21079368
TI  - [Novel method for the measurement of intracellular cAMP levels by using a fusion
      gene of PKA and firefly luciferase].

PMID- 21079369
TI  - [Bench to bedside -past and present of translational research-].

PMID- 21079370
TI  - [Cancer translational research in Japan].

PMID- 21079371
TI  - [Preclinical and clinical findings of the dipeptidyl peptidase-4 inhibitor
      vildagliptin].

PMID- 21079372
TI  - Development of an evidence-based guideline for supervisor training in promoting
      mental health: literature review.
AB  - OBJECTIVE: To review published studies to assess the effects of supervisor
      training on the mental health of subordinate workers, and thereby develop an
      evidence-based guideline for supervisor training in promoting workers' mental
      health. METHOD: Seven studies that assessed the effect of supervisor training,
      whose outcomes included psychological stress responses of (subordinate)
      employees, were retrieved for assessment from PubMed, the Cochrane Library,
      MEDLINE, the Web of Science, and Ichushi-Web. An additional five studies were
      also reviewed for discussion on the content and types of training. RESULTS:
      Providing supervisors with necessary skills and information on mental health,
      including relevant occupational stressors, has a favorable effect on workers'
      mental health, at least in the short term. The subject populations had a
      background of requiring mental health measures. The effect of the training varied
      depending on the participation rate of supervisors, suggesting that the overall
      effect on an organization may be limited without a certain extent of
      participation by supervisors. There is no evidence of a long-term (over 1 yr)
      effect of supervisor training, and the effect of education on the supervisors'
      knowledge and behavior tends to be lost after 6 mo. CONCLUSION: The current
      evidence indicates that the following items should be taken into consideration
      for the development of a guideline for supervisor training: identification of
      high-priority populations requiring education, development of a strategy to
      improve the participation rate in education, inclusion of occupational stressors
      as well as basic information in workplace mental health teaching materials, and
      regular repetition of the program.

PMID- 21079373
TI  - Non-response bias in a surveillance program for asbestos-related lung cancer.
AB  - OBJECTIVES: In a cohort study non-response might lead to a biased selection of
      cohort members and may affect the validity and reliability of the study outcome.
      To detect the possible effects of a non-response bias on study results, we
      evaluated the reasons for non-participation and the differences of respondents
      and non-respondents in a health surveillance program for power industry workers,
      formerly exposed to asbestos. METHODS: A cohort of former power plant workers was
      formed to participate in an early detection program for lung cancer. We evaluated
      the results of 1,019 individuals (mean age 66 yr), of which 839 took part in at
      least one examination, 180 refused to participate or did not respond. To obtain
      the reasons for non-response, we interviewed the cohort members by telephone or
      we requested them by mail to complete and return a brief questionnaire. Further
      sources of information were the communal registration offices and local health
      offices. RESULTS: The main reasons for non-participation were refusal (35%),
      illness (23.3%), death (16.7%) and difficulties with traveling (13.3%). It was
      impossible to make contact with or obtain an explanation from 11.7%. In a
      logistic regression model we demonstrated that advanced age and a long travel
      distance from the study center negatively affected the participation rate
      (p<0.001). There was no difference between respondents and non-respondents
      regarding prevalence (p=0.559) and incidence of lung cancer (p=0.882).
      CONCLUSION: We concluded that in our cohort non-participation did not cause a
      selection bias in terms of lung cancer rates.

PMID- 21079375
TI  - Efficiency of sperm-mediated gene transfer in the ovine by laparoscopic
      insemination, in vitro fertilization and ICSI.
AB  - Transgenesis constitutes an important tool for pharmacological protein production
      and livestock improvement. We evaluated the potential of laparoscopic
      insemination (LI), in vitro fertilization (IVF) and intracytoplasmic sperm
      injection (ICSI) to produce egfp-expressing ovine embryos, using spermatozoa
      previously exposed to pCX-EGFP plasmid in two different sperm/DNA incubation
      treatments: "Long Incubation" (2 h at 17 C) and "Short Incubation" (5 min at 5
      C). For LI, Merino sheep were superovulated and inseminated with treated fresh
      semen from Merino rams. The embryos were recovered by flushing the uterine horns.
      For IVF and ICSI, slaughterhouse oocytes were fertilized with DNA-treated
      frozen/thawed sperm. All recovered embryos were exposed to blue light (488 nm) to
      determine green fluorescent morulae and blastocysts rates. High cleavage and
      morulae/blastocysts rates accompanied the LI and IVF procedures, but no egfp
      expressing embryos resulted. In contrast, regardless of the sperm/plasmid
      incubation treatment, egfp-expressing morulae and blastocysts were always
      obtained by ICSI, and the highest transgenesis rate (91.6%) was achieved with
      Short Incubation. In addition, following the incubation of labeled plasmid DNA,
      after Long or Short exposure treatments, with fresh or frozen/thawed spermatozoa,
      only non-motile fresh spermatozoa could maintain an attached plasmid after
      washing procedures. No amplification product could be detected following PCR
      treatment of LI embryos whose zonae pellucidae (ZP) had been removed. In order to
      establish conditions for transgenic ICSI in the ovine, we compared three
      different activation treatments, and over 60% of the obtained blastocysts
      expressed the transgene. For ICSI embryos, FISH analysis found possible signals
      compatible with integration events. In conclusion, our results show that in the
      ovine, under the conditions studied, ICSI is the only method capable of producing
      exogenous gene-expressing embryos using spermatozoa as vectors.

PMID- 21079374
TI  - A brief cognitive-behavioral stress management program for secondary school
      teachers.
AB  - OBJECTIVE: This study aimed to assess the efficacy of a brief cognitive
      behavioral program that was designed to reduce the work-related stress levels of
      secondary school teachers. METHODS: A quasi-experimental design was used to
      compare the intervention groups with the wait-list control groups. Seventy
      teachers from the intervention groups and 54 from the control groups completed a
      set of validated scales at the baseline and 3-4 wk later. The scales included the
      Depression Anxiety Stress Scale, the Dysfunctional Attitude Scale-Form A, the
      Health-Promoting Lifestyle Profile II, and the Occupational Stress Inventory
      Revised Edition. RESULTS: After controlling for the baseline measures, the
      intervention groups had significantly lower role stress, personal strain and
      overall work-related stress 3-4 wk after the baseline measurements. The
      intervention groups also had significantly higher stress management behaviors,
      and less general stress and dysfunctional thoughts than the control groups (all
      p<=0.05). The levels of dysfunctional thoughts and stress management behaviors
      significantly predicted general stress after intervention and personal resource
      deficits. The level of dysfunctional thoughts also predicted the personal strain
      of work-related stresses (all p<0.05). CONCLUSIONS: The brief program reported in
      this study was efficacious in reducing the work-related stress of secondary
      teachers. Teachers experienced less work-related stress after the program, and
      they reported reduced dysfunctional thoughts and enhanced stress management
      behaviors. This program may be considered as an initial strategy for teachers to
      develop skills to cope with their work-related stress in the short term and could
      be incorporated with other strategies to achieve longer-term effects.

PMID- 21079376
TI  - Optimized cryopreservation of mouse sperm based on fertilization rate.
AB  - Although procedures for in vitro fertilization with cryopreserved sperm have been
      published there is a lack of data indicating that the cryoprotectant and
      cryopreservation procedures used for those procedures were optimal. To redress
      this, fertilization rate of eggs exposed to sperm in vitro was used as the
      outcome in the optimization of raffinose concentration in the cryoprotectant
      (raffinose in water), volume of cryoprotectant, and freezing conditions for
      C57BL/6J mouse sperm. Sperm were frozen in a cylindrical Dewar with an internal
      diameter and height of 14.0 cm and 36.0 cm respectively. The optimal
      concentration of raffinose was 23-24% (510-540 mOsm/kg). The optimal volume of
      cryoprotectant used to prepare the sperm suspension from a single mouse was 180
      400 ul, and sperm proved most fertile when frozen 13-25 mm above liquid nitrogen.
      Raffinose in the fertilization medium did not inhibit fertilization. Fertilized
      eggs transferred to oviducts of recipient mice developed into viable offspring.

PMID- 21079377
TI  - Derivation of histocompatible stem cells from ovarian tissue.
AB  - Somatic cell nuclear transfer, the first established technique for producing
      patient-specific autologous stem cells, inevitably requires the sacrifice of
      viable embryos. To circumvent the serious ethical issues associated with this use
      of embryos, researchers have developed several alternative methods for the
      production of histocompatible stem cells. In our research, we have used two
      methods to derive histocompatible stem cells from murine ovarian tissue. First,
      we have established autologous stem cells by culturing degeneration-fated
      preantral follicles to produce developmentally competent, mature oocytes and then
      parthenogenetically activating these mature oocytes to acquire genetic
      homogeneity. Second, we have used cell-to-cell interactions to derive stem cells
      from ovarian stromal cells without undertaking genetic modification. We have
      successfully derived autologous murine stem cells by manipulating primary and
      early secondary follicles in vitro, and this method has proved successful even
      for follicles retrieved from aged ovaries. Furthermore, we believe that it will
      be possible to isolate stem cells directly from non-germline ovarian tissue or to
      derive stem cells by culturing the ovarian cells with other somatic cells. If
      achieved, these aims will greatly advance the development of induced pluripotent
      stem cell technology, as well as tissue-specific stem cell research. In this
      review, we introduce the relevant technologies for establishing histocompatible
      stem cells from ovarian tissue cells without undertaking genetic manipulation and
      review the current limitations of, and future research directions in, stem cell
      biology.

PMID- 21079378
TI  - Relationship between radiosensitivity of human neonatal hematopoietic
      stem/progenitor cells and individual maternal/neonatal obstetric factors.
AB  - Hematopoietic stem/progenitor cells (HSPCs) in placental/umbilical cord blood
      (CB), which is neonatal peripheral blood, have increasingly been used for
      hematopoietic stem cell transplantations. It is likely HSPCs are sensitive to
      extracellular oxidative stresses, such as ionizing radiation and redox-directed
      chemotherapeutic agents. However, the radiosensitivity of HSPCs and neonatal
      hematopoietic system remains unclear. This study investigated the potential
      relationship between the radiosensitivity of HSPCs in CB, which was obtained from
      singleton and full-term deliveries, and maternal/neonatal obstetric factors.
      Freshly prepared CB CD34(+) cells exposed to 2 Gy X-irradiation were assayed for
      hematopoietic progenitor cells such as colony-forming unit-granulocyte-macrophage
      (CFU-GM), burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte
      erythroid-macrophage-megakaryocyte (CFU-Mix), and colony-forming unit
      megakaryocyte (CFU-Meg). As a result, the neonatal weight, placental weight, CB
      volume, total low-density (LD) cells, and CD34(+) cells showed mutually
      significant positive correlations. The CB volume and total LD cells showed a
      significant reverse correlation with the surviving fraction of CFU-Meg. The
      surviving fraction of CFU-GM in spring (March-May) was significantly higher than
      that in autumn (September-November). The surviving fraction of CFU-Meg in the
      spring was significantly lower than that in the autumn. Male neonates showed a
      significantly higher surviving fraction of CFU-GM than female neonates.
      Contrarily, females showed a significantly higher surviving fraction of CFU-Meg
      than males. The present results suggest that the obstetric factors, such as the
      season of birth and neonatal gender, influence the radiosensitivity of neonatal
      hematopoiesis.

PMID- 21079379
TI  - Clorgyline inhibits orexin-A-induced arousal in layer-type chicks.
AB  - We previously demonstrated that intracerebroventricular (ICV) injection of orexin
      A induces arousal and increased metabolic turnover rates of norepinephrine,
      dopamine, and serotonin in layer (egg-type) chicks. Because monoamine oxidase-A
      (MAO-A) is a potent degrading enzyme of these monoamines, we hypothesized that
      orexin-A may mediate its arousal-inducing effects through MAO-A. Therefore, we
      simultaneously injected clorgyline, a specific inhibitor of MAO-A, with orexin-A
      and examined behavior of chicks. Behaviors associated with arousal were
      attenuated in the group of chicks that received clorgyline and orexin-A compared
      with those that received orexin-A alone. For the monoamine turnover rate,
      enhancement of the turnover rate of serotonin by orexin-A was attenuated by
      clorgyline. Therefore, we conclude that orexin-A-induced arousal is dependent
      upon monoamine neural activities stimulated by MAO-A in chicks.

PMID- 21079380
TI  - Treatment with nesiritide, a recombinant B-type natriuretic Peptide, reduces
      vascular remodeling following balloon-induced endothelial injuries in rabbits.
AB  - Re-stenosis or remodeling of coronary and peripheral arteries remains a major
      complication following balloon-angioplasty or stenting. This study was designed
      to investigate the effect of nesiritide, a recombinant B-type natriuretic peptide
      (BNP), on vascular remodeling following balloon-induced endothelial injuries.
      Twenty-eight male New Zealand rabbits were divided into nesiritide-treated (0.1
      mg/kg/day, sc, for 4 weeks, n = 10), saline-treated control (n = 10) and sham
      operated groups (n = 8). In the nesiritide and control groups, a balloon catheter
      was inserted to the right iliac artery to induce injuries. Vascular endothelial
      growth factor (VEGF) was measured by immunohistochemistry. The area under
      internal elastic membrane of the arterial wall (643.2 +/- 134.1 vs 493.7 +/-
      139.3 um(2), p < 0.05) and the area under external elastic membrane (1495.1 +/-
      204.9 vs 1265.9 +/- 232.6 um(2), p < 0.05) in the nesiritide group were greater
      than those in the control group, but were smaller than those in the sham-operated
      group (p < 0.05). The stenosis ratio was lower in the nesiritide group than in
      the control group (18.7 +/- 7.7% vs 38.0 +/- 8.3%, p < 0.01). Importantly, the
      VEGF expression rate was significantly lower in the nesiritide group than in the
      control group (42.2 +/- 8.8% vs 56.1 +/- 13.1%, p < 0.05), while there were no
      signs of VEGF expression in the non-injured arteries of the three groups. In
      conclusion, nesiritide treatment reduces the stenosis of the rabbit iliac artery
      following balloon-induced endothelial injuries probably by decreasing VEGF
      expression.

PMID- 21079381
TI  - Validated methods of cough assessment: a systematic review of the literature.
AB  - BACKGROUND: Cough is a common symptom for which patients often seek medical
      advice and consume vast amounts of drugs. It is a real challenge for both the
      physician and the clinical researcher to evaluate a cough's clinical importance
      and its precise response to treatment. OBJECTIVES: This systematic literature
      review has the following objectives: first, to make an inventory of the validated
      tools for assessing cough, and second, to investigate the extent to which the
      results of various assessment methods can be correlated. METHODS: Two independent
      investigators searched the Medline, Embase, and Cochrane databases for validation
      studies on cough assessment tools. RESULTS: Thirty-four studies were included.
      Several ambulatory cough monitors automatically identify cough and have been
      validated in a limited number of patients. Three cough-specific quality-of-life
      scales (Leicester Cough Questionnaire, Cough Quality of Life Questionnaire, and
      Burden of Cough Questionnaire) have been validated. No validation studies of
      descriptive scores or visual analogue scales were found. The correlations between
      quality-of-life scores and cough frequency were good. The correlations between
      descriptive scores or visual analogue scales and more objective methods, such as
      cough frequency monitoring or quality-of-life scores, were inconsistent.
      CONCLUSION: Cough-specific quality-of-life questionnaires can provide valid
      outcomes for research into cough. Although the current developments in cough
      monitoring devices are promising, further studies on a larger scale, under more
      realistic conditions, and for different patterns of cough are required before
      they can be recommended for widespread use.

PMID- 21079382
TI  - Quantitative assessment of brain volumes in fish: comparison of methodologies.
AB  - When correlating brain areas with behavioral and environmental characteristics, a
      variety of techniques are employed. In fishes (elasmobranchs and teleosts), 2
      methods, histology and the idealized ellipsoid and/or half-ellipsoid technique,
      are primarily used to calculate the volume of a brain area and therefore its
      relationship to social or ecological complexity. In this study on a perciform
      teleost, we have quantitatively compared brain volumes obtained using the
      conventional techniques of histology and approximating brain volume to an
      idealized ellipsoid (or half ellipsoid) and magnetic resonance imaging, an
      established clinical tool typically used for assessing brain volume in other
      vertebrates. Our results indicate that, when compared to brain volumes measured
      using magnetic resonance imaging of brain regions in situ, variations in brain
      shape and histological artifacts can lead to significant differences in brain
      volume, especially in the telencephalon and optic tecta. Consequently, in
      comparative studies of brain volumes, we advise caution when using the
      histological and/or ellipsoid methods to make correlations between brain area
      size and environmental, behavioral and social characteristics and, when possible,
      we propose the use of magnetic resonance imaging.

PMID- 21079383
TI  - C-Banding/DAPI and in situ hybridization reflect karyotype structure and sex
      chromosome differentiation in Humulus japonicus Siebold & Zucc.
AB  - Japanese hop (Humulus japonicus Siebold & Zucc.) was karyotyped by chromosome
      measurements, fluorescence in situ hybridization with rDNA and telomeric probes,
      and C-banding/DAPI. The karyotype of this species consists of sex chromosomes (XX
      in female and XY1Y2 in male plants) and 14 autosomes difficult to distinguish by
      morphology. The chromosome complement also shows a rather monotonous terminal
      distribution of telomeric repeats, with the exception of a pair of autosomes
      possessing an additional cluster of telomeric sequences located within the
      shorter arm. Using C-banding/DAPI staining and 5S and 45S rDNA probes we
      constructed a fluorescent karyotype that can be used to distinguish all autosome
      pairs of this species except for the 2 largest autosome pairs, lacking rDNA
      signals and having similar size and DAPI-banding patterns. Sex chromosomes of H.
      japonicus display a unique banding pattern and different DAPI fluorescence
      intensity. The X chromosome possesses only one brightly stained AT-rich terminal
      segment, the Y1 has 2 such segments, and the Y2 is completely devoid of DAPI
      signal. After C-banding/DAPI, both Y chromosomes can be easily distinguished from
      the rest of the chromosome complement by the increased fluorescence of their
      arms. We discuss the utility of these methods for studying karyotype and sex
      chromosome evolution in hops.

PMID- 21079384
TI  - GSTT1: a marker of the aggressiveness of bladder cancer.
AB  - INTRODUCTION: Glutathione S-transferases have been implicated in the development
      of bladder cancer (BC). We investigated the genotype and expression of
      glutathione S-transferase-mu (GSTM1) and glutathione S-transferase-theta (GSTT1)
      in BC tissue specimens. MATERIALS AND METHODS: Tumor samples and matched normal
      mucosae were obtained from 34 patients. Genomic DNA was used to analyze GSTM1 and
      GSTT1 genotypes using multiplex polymerase chain reaction. GSTM1 and GSTT1 mRNA
      levels were measured using real-time reverse transcriptase polymerase chain
      reaction. RESULTS: GSTM1 mRNA expression was lower in tumor tissues than in
      matched normal bladder mucosae, whereas GSTT1 mRNA expression was significantly
      higher. GSTT1 mRNA expression was higher in muscle-invasive BC and high-grade
      cancers than in non-muscle-invasive BC and lower-grade tumors. CONCLUSIONS: GSTT1
      is correlated with characteristics of aggressive BC. GSTT1 may play an important
      role in tumorigenesis and disease progression in patients with BC.

PMID- 21079385
TI  - Prediction of small-for-gestation neonates from biophysical and biochemical
      markers at 11-13 weeks.
AB  - OBJECTIVE: To develop a model for prediction of small-for-gestational age (SGA)
      neonates in the absence of preeclampsia (PE) based on maternal factors and
      biophysical and biochemical markers at 11-13 weeks' gestation. METHODS: Screening
      study in 1,536 SGA and 31,314 non-SGA pregnancies based on maternal
      characteristics, fetal nuchal translucency (NT) thickness, serum pregnancy
      associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin
      (beta-hCG). We also measured mean arterial pressure (MAP), uterine artery
      pulsatility index (PI) and performed case-control studies for measurement of
      maternal serum concentration of placental growth factor (PLGF), placental protein
      13 (PP13) and A Disintegrin And Metalloprotease (ADAM12). Regression analysis was
      used to develop a model for the prediction of SGA. RESULTS: In the SGA group,
      uterine artery PI and MAP were increased and serum PAPP-A, free beta-hCG, PLGF,
      PP13, and ADAM12 and fetal NT were decreased. At a false positive rate of 10%,
      the estimated detection rate by a combination of maternal factors and biophysical
      and biochemical markers at 11-13 weeks was 73% for SGA requiring delivery before
      37 weeks and 46% for those delivering at term. CONCLUSIONS: Half of pregnancies
      with SGA neonates in the absence of PE could potentially be identified at 11-13
      weeks.

PMID- 21079386
TI  - Short adult stature and overweight are associated with poor intellectual
      performance in subjects born preterm.
AB  - BACKGROUND/AIMS: To study the association between preterm birth and adult
      intellectual performance, with special emphasis on the influence of postnatal
      growth. METHODS: A population-based cohort study was performed on 272,046 males,
      born between 1973 and 1978, of whom 248,447 were conscripted for military service
      between 1991 and 1997. Birth characteristics were obtained from the Swedish
      Medical Birth Register and information on intellectual performance, final height
      and BMI were taken from the Swedish Conscript Register. Multiple logistic
      regression analysis was performed. RESULTS: At conscription, males born preterm
      had lower results at tests of intellectual performance compared to those born at
      term. Short adult stature among these males enhanced the risk of low intellectual
      performance, as compared to those with normal adult stature. Moreover, a high
      adult BMI in the males born preterm was associated with an increased risk of
      subnormal performance as compared to those with normal BMI. CONCLUSIONS: Subjects
      born preterm had poorer intellectual performance than those born at term. Short
      adult stature or a high BMI was associated with an even higher risk for poor
      intellectual performance in the subjects born preterm. This indicates the
      occurrence of common mechanisms underlying growth and cognitive development.

PMID- 21079387
TI  - Perinatal exposure to high-fat diet programs energy balance, metabolism and
      behavior in adulthood.
AB  - The perinatal environment plays an important role in programming many aspects of
      physiology and behavior including metabolism, body weight set point, energy
      balance regulation and predisposition to mental health-related disorders such as
      anxiety, depression and attention deficit hyperactivity disorder. Maternal health
      and nutritional status heavily influence the early environment and have a long
      term impact on critical central pathways, including the melanocortinergic,
      serotonergic system and dopaminergic systems. Evidence from a variety of animal
      models including rodents and nonhuman primates indicates that exposure to
      maternal high-fat diet (HFD) consumption programs offspring for increased risk of
      adult obesity. Hyperphagia and increased preference for fatty and sugary foods
      are implicated as mechanisms for the increased obesity risk. The effects of
      maternal HFD consumption on energy expenditure are unclear, and future studies
      need to address the impact of perinatal HFD exposure on this important component
      of energy balance regulation. Recent evidence from animal models also indicates
      that maternal HFD consumption increases the risk of offspring developing mental
      health-related disorders such as anxiety. Potential mechanisms for perinatal HFD
      programming of neural pathways include circulating factors, such as hormones
      (leptin, insulin), nutrients (fatty acids, triglycerides and glucose) and
      inflammatory cytokines. As maternal HFD consumption and obesity are common and
      rapidly increasing, we speculate that future generations will be at increased
      risk for both metabolic and mental health disorders. Thus, it is critical that
      future studies identify therapeutic strategies that are effective at preventing
      maternal HFD-induced malprogramming.

PMID- 21079388
TI  - Impact of gsp oncogene on the mRNA content for somatostatin and dopamine
      receptors in human somatotropinomas.
AB  - INTRODUCTION: It has been reported in some series that gsp+ somatotropinomas are
      more sensitive to somatostatin analogues (SA) and dopamine's actions which may be
      related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile.
      No previous studies have been undertaken to evaluate the SSTR and DR profile
      related with the gsp status in somatotropinomas. OBJECTIVES: To determine if (1)
      gsp status is correlated with response to octreotide LAR (LAR) and tumor
      expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate
      SSTR and DR mRNA levels. METHODS: Response to SA was evaluated by GH and IGF-I
      percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR
      and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was
      used to determine SSTR and DR tumor expression. Primary pituitary cell cultures
      of primates were used to study whether SSTR and DR expression is regulated by
      forskolin. RESULTS: The response to LAR did not significantly differ between
      patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels
      of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1,
      SSTR2, DR1 and DR2 expression in cell cultures. CONCLUSION: Elevated SSTR1,
      SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA
      therapy; however, this study may not have been appropriately powered to observe
      significant effects in the clinical response. Elevated cAMP levels could be
      directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels
      observed in gsp+ patients.

PMID- 21079389
TI  - Relative validity and reproducibility of a food frequency questionnaire designed
      for French adults.
AB  - OBJECTIVES/AIMS: We tested the reproducibility and relative validity of a French
      self-administered food frequency questionnaire (FFQ) against 24-hour dietary
      records (DRs). METHODS: We selected 140 participants from the SU.VI.MAX study.
      They filled in the FFQ twice at 1-year intervals and completed monthly 24-hour DR
      during that year. The number of food items in the FFQ was 240. RESULTS:
      Reproducibility was high. Medians of Pearson coefficients were 0.70 and 0.65 for
      nutrients in men and women, respectively. Medians of intraclass correlation
      coefficients for food were 0.62 in men and 0.65 in women. For nutrients, crude
      Pearson correlation coefficients for relative validity ranged from 0.28 to 0.67
      in men and from 0.25 to 0.55 in women. The Spearman coefficient for alcohol was
      0.78 in both genders. For food, the medians of the Spearman coefficient were 0.49
      and 0.45 for men and women, respectively. Complete disagreement between the FFQ
      and 24-hour DRs for ranking subjects according to food consumption was low (about
      4%), except for rarely consumed food groups, that is nuts, legumes and offal.
      Calibration coefficients were estimated by linear regression. All coefficients
      were lower than one. CONCLUSIONS: Acceptable reproducibility and relative
      validity were observed in a FFQ designed for French adults.

PMID- 21079390
TI  - Polymorphism Ala54Thr of fatty acid-binding protein 2: Allelic frequencies and
      influence on cardiovascular risk factors in a multicenter study of Castilla y
      Leon.
AB  - BACKGROUND: A transition of guanin to alanin at codon 54 of the fatty acid
      binding protein 2 gene (FABP2) results in an amino acid substitution (Ala54 to
      Thr54). This polymorphism was associated with some cardiovascular risk factors.
      OBJECTIVE: The aim of our study was to investigate the influence of the Thr54
      polymorphism in the FABP2 gene on obesity anthropometric parameters and
      cardiovascular risk factors in the fasted state in obese subjects and the allelic
      distribution of this polymorphism in a geographic area of Spain. DESIGN: A
      population of 264 obese subjects was analyzed in a cross-sectional study from all
      health centers of Castilla y Leon (Spain). A nutritional and biochemical
      evaluation was performed. The statistical analysis was performed for the combined
      Ala54/Thr54 and Thr54/Thr54 genotype as a dominant model. RESULTS: The mean age
      was 41.1 +/- 13.1 years and the mean BMI 36.5 +/- 5.9, with 94 males (35.6%) and
      170 females (74.4%). One hundred and fifty-three subjects (58%) had the genotype
      Ala54/Ala54 (wild-type group) and 111 (42%) participants had the genotype
      Ala54/Thr54 (n = 92, 34.8%) or Thr54/Thr54 (n = 19, 7.2%) (mutant-type group).
      The health area of Valladolid had a lower frequency of wild-type genotype and
      Ala54 allelic frequency than all the other health areas of Castilla y Leon. C
      reactive protein was higher in the mutant-type than the wild-type group (3.4 +/-
      5.6 vs. 7.9 +/- 10.4 mg/dl; p < 0.05). CONCLUSION: The finding of this study is
      the association of the Thr54/Ala54 and Thr54/Thr54 FABP2 phenotypes with higher
      levels of C-reactive protein without relation to insulin resistance. Frequencies
      of this polymorphism are different among health areas of Castilla y Leon.

PMID- 21079391
TI  - Upregulation of lipogenesis and protein tyrosine phosphatase-1B expression in the
      liver of Wistar rats with metabolic syndrome chronically induced by drinking
      sucrose water.
AB  - BACKGROUND: Establishing animal models with metabolic disorders similar to human
      metabolic syndrome (MS) is important. In terms of eliciting a full array of MS,
      we have previously shown that Wistar rats are more responsive to sucrose water
      drinking than are C57BL/6J mice. This study was aimed at investigating the
      underlying molecular mechanism of sucrose water-induced MS in Wistar rats.
      METHODS: Male Wistar rats were divided into 2 groups (n = 8 for each group) which
      were given plain water (C group) or 30% sucrose water (SW group) to drink ad
      libitum. After 20 weeks, the transcriptional levels and protein translocation of
      hepatic sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate
      response element-binding protein (ChREBP) as well as the protein levels of
      protein tyrosine phosphatase-1B (PTP-1B) in insulin-responsive tissues (liver,
      muscle, and adipose tissue) were measured. RESULTS: The sucrose water regimen
      successfully elicited visceral obesity, hypertriglyceridemia, insulin resistance,
      and high blood pressure. The upregulation of de novo lipogenesis in the liver of
      the sucrose water-treated rats was demonstrated by an increased activity of
      enzymes, mRNA levels of lipogenic proteins, and nuclear levels of SREBP-1c and
      ChREBP. Moreover, in the sucrose water-treated rats, protein levels of PTP-1B
      were significantly increased in liver and skeletal muscle but decreased in
      adipose tissue. CONCLUSION: The susceptibility of Wistar rats to sucrose water
      induced MS is associated with the transactivation of SREBP-1c and ChREBP in the
      liver, and PTP-1B is involved in the upregulation of de novo lipogenesis in the
      liver and the pathology of systemic insulin resistance in rats with MS
      chronically induced by drinking sucrose water.

PMID- 21079392
TI  - Auditory brainstem response changes during exposure to GSM-900 radiation: an
      experimental study.
AB  - The objective of the present study was to investigate the possible
      electrophysiological time-related changes in auditory pathway during mobile phone
      electromagnetic field exposure. Thirty healthy rabbits were enrolled in an
      experimental study of exposure to GSM-900 radiation for 60 min and auditory
      brainstem responses (ABRs) were recorded at regular time-intervals during
      exposure. The study subjects were radiated via an adjustable power and frequency
      radio transmitter for GSM-900 mobile phone emission simulation, designed and
      manufactured according to the needs of the experiment. The mean absolute latency
      of waves III-V showed a statistically significant delay (p < 0.05) after 60, 45
      and 15 min of exposure to electromagnetic radiation of 900 MHz, respectively.
      Interwave latency I-III was found to be prolonged after 60 min of radiation
      exposure in correspondence to wave III absolute latency delay. Interwave
      latencies I-V and III-V were found with a statistically significant delay (p <
      0.05) after 30 min of radiation. No statistically significant delay was found for
      the same ABR parameters in recordings from the ear contralateral to the radiation
      source at 60 min radiation exposure compared with baseline ABR. The ABR
      measurements returned to baseline recordings 24 h after the exposure to
      electromagnetic radiation of 900 MHz. The prolongation of interval latencies I-V
      and III-V indicates that exposure to electromagnetic fields emitted by mobile
      phone can affect the normal electrophysiological activity of the auditory system,
      and these findings fit the pattern of general responses to a stressor.

PMID- 21079393
TI  - Adult neurogenesis in the hedgehog (Erinaceus concolor) and mole (Talpa
      europaea).
AB  - We investigated adult neurogenesis in two species of mammals belonging to the
      superorder Laurasiatheria, the southern white-breasted hedgehog (order
      Erinaceomorpha, species Erinaceus concolor) from Armenia and the European mole
      (order Soricomorpha, species Talpa europaea) from Poland. Neurogenesis in the
      brain of these species was examined immunohistochemically, using the endogenous
      markers doublecortin (DCX) and Ki-67, which are highly conserved among species.
      We found that in both the hedgehog and mole, like in the majority of earlier
      investigated mammals, neurogenesis continues in the subventricular zone (SVZ) of
      the lateral ventricles and in the dentate gyrus (DG). In the DG of both species,
      DCX-expressing cells and Ki-67-labeled cells were present in the subgranular and
      granular layers. In the mole, a strong bundle of DCX-labeled processes,
      presumably axons of granule cells, was observed in the center of the hilus.
      Proliferating cells (expressing Ki-67) were identified in the SVZ of lateral
      ventricles of both species, but neuronal precursor cells (expressing DCX) were
      also observed in the olfactory bulb (OB). In both species, the vast majority of
      cells expressing DCX in the OB were granule cells with radially orientated
      dendrites, although some periglomerular cells surrounding the glomeruli were also
      labeled. In addition, this paper is the first to show DCX-labeled fibers in the
      anterior commissure of the hedgehog and mole. These fibers must be axons of new
      neurons making interhemispheric connections between the two OB or piriform
      (olfactory) cortices. DCX-expressing neurons were observed in the striatum and
      piriform cortex of both hedgehog and mole. We postulate that in both species a
      fraction of cells newly generated in the SVZ migrates along the rostral migratory
      stream to the piriform cortex. This pattern of migration resembles that of the
      'second-wave neurons' generated during embryonal development of the neocortex
      rather than the pattern observed during development of the allocortex. In spite
      of the presence of glial cells alongside DCX-expressing cells, we never found
      colocalization of DCX protein with a glial marker (vimentin or glial fibrillary
      acidic protein).

PMID- 21079394
TI  - Retinal ganglion cell layer of the Caspian seal Pusa caspica: topography and
      localization of the high-resolution area.
AB  - Retinal topography, cell density and sizes of ganglion cells in the Caspian seal
      (Pusa caspica) were analyzed in retinal whole mounts stained with cresyl-violet.
      The topographic distribution of ganglion cells displayed an area of high cell
      density located in the temporal quadrant of the retina and was similar to the
      area centralis of terrestrial carnivores. It extended nasally, above the optic
      disk, as a streak of increased cell density. In different whole mounts, the peak
      cell density in the high-density area ranged from 1,684 to 1,844 cells/mm2 (mean
      1,773 cells/mm2). The cell density data predict a retinal resolution of around
      8.5 cycles/degree in water. A distinctive feature of the Caspian seal's retina is
      the large size of ganglion cells and the low cell density compared to terrestrial
      mammals. The ganglion cell diameter ranged from 10 to 58 MUm. Cell size
      histograms featured bimodal patterns with groups of small and large ganglion
      cells. The large cells appeared similar to alpha-cells of terrestrial mammals and
      constituted 7% of the total ganglion cell population.

PMID- 21079395
TI  - Extensive changes in the expression of the opioid genes between humans and
      chimpanzees.
AB  - The various means by which the body perceives, transmits, and resolves the
      experiences of pain and nociception are mediated by a host of molecules,
      including neuropeptides within the opioid gene signaling pathway. The peptide
      ligands and receptors encoded by this group of genes have been linked to
      behavioral disorders as well as a number of psychiatric affective disorders. Our
      aim was to explore the recent evolutionary history of these two gene families by
      taking a comparative genomics approach, specifically through a comparison between
      humans and chimpanzees. Our analyses indicate differential expression of these
      genes between the two species, more than expected based on genome-wide
      comparisons, indicating that differential expression is pervasive among the
      opioid genes. Of the 8 family members, three genes showed significant expression
      differences (PENK, PNOC, and OPRL1), with two others marginally significant
      (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee
      lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between
      the human and chimpanzee branches are consistent with positive selection.
      Collectively, these results suggest that there may have been a selective
      advantage to modulating the expression of the opioid genes in humans compared
      with our closest living relatives. Information about the cognitive roles mediated
      by these genes in humans may help to elucidate the trait consequences of these
      putatively adaptive expression changes.

PMID- 21079396
TI  - Guanidino compounds as cause of cardiovascular damage in chronic kidney disease:
      an in vitro evaluation.
AB  - Chronic kidney disease is considered a major cause of cardiovascular risk and non
      traditional risk factors remain largely unknown. The in vitro toxicity of 10
      guanidino compounds (GCs) was evaluated via a standardized approach on different
      cell systems of relevance in cardiovascular disease. The parameters evaluated
      were production of reactive oxygen species, expression of surface molecules, cell
      proliferation, cytotoxicity and calcification. Several GCs had a stimulatory
      effect on monocytes and granulocytes (SDMA, creatine and guanidinobutyric acid
      (GBA)). Some GCs (guandine (G), guanidinosuccinic acid (GSA) and SDMA) inhibited
      endothelial cell proliferation or reduced calcification in osteoblast-like human
      VSMC (ADMA, GSA and SDMA). Stimulation of osteoclastogenesis could be
      demonstrated for ADMA, G, guanidinoacetic acid and GBA in a RAW264.7 cell line.
      No compounds were cytotoxic to AoSMC or endothelial cells, nor influenced their
      viability. GCs, especially SDMA, likely contribute to cardiovascular
      complications in uremia, mainly those related to microinflammation and leukocyte
      activation.

PMID- 21079397
TI  - Post-thrombolytic hyperglycemia and 3-month outcome in acute ischemic stroke.
AB  - BACKGROUND: Treating hyperglycemia in acute ischemic stroke may be beneficial,
      but knowledge on its prognostic value and optimal target glucose levels is
      scarce. We investigated the dynamics of glucose levels and the association of
      hyperglycemia with outcomes on admission and within 48 h after thrombolysis.
      METHODS: We included 851 consecutive patients with acute ischemic stroke treated
      with intravenous thrombolysis in the Helsinki University Central Hospital during
      1998-2008. Outcome measures were unfavorable 3- month outcome (3-6 on the
      modified Rankin Scale), death, and symptomatic intracerebral hemorrhage (sICH)
      according to NINDS criteria. Hyperglycemia was defined as a blood glucose level
      of >=8.0 mmol/l. Four groups were identified based on (a) admission and (b) peak
      glucose levels 48 h after thrombolysis: (1) persistent normoglycemia (baseline
      plus 48-hour normoglycemia), (2) baseline hyperglycemia (48-hour normoglycemia),
      (3) 48-hour hyperglycemia (baseline normoglycemia), and (4) persistent
      hyperglycemia (baseline plus 48-hour hyperglycemia). RESULTS: 480 (56.4%) of our
      patients (median age 70 years; onset-to-needle time 199 min; National Institutes
      of Health Stroke Scale score 9), had persistent normoglycemia, 59 (6.9%) had
      baseline hyperglycemia, 175 (20.6%) had 48-hour hyperglycemia, while persistent
      hyperglycemia appeared in 137 (16.1%) patients. Persistent and 48-hour
      hyperglycemia independently predicted unfavorable outcome [odds ratio (OR) =
      2.33, 95% confidence interval (CI) = 1.41-3.86, and OR = 2.17, 95% CI = 1.30
      3.38, respectively], death (OR = 6.63, 95% CI = 3.25-13.54, and OR = 3.13, 95% CI
      = 1.56-6.27, respectively), and sICH (OR = 3.02, 95% CI = 1.68-5.43, and OR =
      1.89, 95% CI = 1.04-3.43, respectively), whereas baseline hyperglycemia did not.
      CONCLUSIONS: Hyperglycemia (>=8.0 mmol/l) during 48 h after intravenous
      thrombolysis of ischemic stroke is strongly associated with unfavorable outcome,
      sICH, and death.

PMID- 21079398
TI  - Serum calcium levels and long-term mortality in patients with acute stroke.
AB  - BACKGROUND: Calcium concentrations in serum are maintained within an exquisitely
      narrow range. Our aim was to examine the association between serum calcium and
      albumin-adjusted calcium (calcium(adj)) levels and stroke outcome in a cohort of
      unselected patients with acute stroke. METHODS: Consecutive patients hospitalized
      due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large
      medical center were systematically assessed and followed for 1 year. Baseline
      total calcium and calcium(adj) levels were collapsed into groups of low (<8.6
      mg/dl), normal (8.7-9.9 mg/dl) and high (>10 mg/dl) levels and linear and
      quadratic relations with outcome were examined. RESULT: Among 784 patients (mean
      age 70.7 +/- 12.5 years, 42.5% females), the mean +/- SD total calcium level was
      9.3 +/- 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all
      cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22-2.75] among
      patients with low versus normal levels. For calcium(adj), the adjusted HR for all
      cause death among women was over 3-fold higher among patients with high
      calcium(adj) levels versus those with normal levels (3.31; 95% CI 1.70-6.46),
      while no such associations were observed among men. In models developed to
      estimate the linear and quadratic relations, each unit increment in total calcium
      squared was associated with an increased adjusted HR of all-cause death over 1
      year (p = 0.02) confirming nonlinear associations, and each unit increment in
      calcium(adj) squared was associated with an increased adjusted HR of all-cause
      death over 1 year among women (p < 0.001) but not among men (p = 0.70).
      CONCLUSIONS: Serum calcium concentrations are a marker of mortality in acute
      stroke patients, but the associations are not linear, increasing at both extremes
      of calcium levels. Our findings suggest that long-term survival is optimal in a
      distinct range of serum calcium levels.

PMID- 21079399
TI  - Blood pressure and total cholesterol level are critical risks especially for
      hemorrhagic stroke in Akita, Japan.
AB  - BACKGROUND AND PURPOSE: Stroke risk factors differ depending on the subtype of
      stroke; moreover, the distribution of risks is different among countries and
      races. METHODS: Mass health screening data were collected from the Akita
      Prefectural Federation of Agricultural Cooperative for Health and Welfare from
      1991 to 1998. Cerebrovascular events were determined from the Akita stroke
      registry from 1991 to 2001. Then, clinical risk factors for stroke, such as
      hypertension, hyperlipidemia and diabetes mellitus, were assessed in the
      different subtypes of stroke. RESULTS: A total of 156,892 persons were included
      in this study (76,330 men and 80,562 women), and 1,323 subjects had a stroke
      during the 3 years of the screening period. The distribution of subtypes such as
      cerebral hemorrhage (CH), cerebral infarction (CI) and subarachnoid hemorrhage
      (SAH) was 27.3, 55.9 and 16.8%, respectively. Mean age and systolic and diastolic
      blood pressures (BPs) were significantly higher in stroke cases. CH and CI
      occurred more frequently in men, whereas SAH occurred more frequently in women.
      Serum total cholesterol (TC) <160 mg/dl was a risk factor for hemorrhagic stroke
      (CH and SAH), whereas TC >280 mg/dl increased the risk of CI. A multivariable
      analysis revealed that the lower TC level (<160 mg/dl) and the higher BP
      increased the relative risk of hemorrhagic stroke. CONCLUSIONS: BP was the
      strongest risk factor for any subtype of stroke. High BP and low TC (<160 mg/dl)
      were critical risks of hemorrhagic stroke.

PMID- 21079400
TI  - The value of tumor markers in evaluating chemotherapy response and prognosis in
      Chinese patients with advanced non-small cell lung cancer.
AB  - OBJECTIVE: The aim of this study was to assess the value of tumor markers in
      monitoring chemotherapy response and predicting prognosis in patients with
      advanced non-small cell lung cancer (NSCLC). METHODS: We studied carcinoembryonic
      antigen (CEA), CYFRA21-1 and neuron-specific enolase (NSE) of 111 untreated
      patients with advanced NSCLC before and after 2 cycles of chemotherapy, meanwhile
      evaluating the response according to the image, and analyzed the relationship
      between tumor markers and response rate, time to progression (TTP) and overall
      survival (OS). RESULTS: The mean percentages of CEA decrease of the 111 patients
      with advanced NSCLC whose image response was partial response, no response and
      progressive disease were 22.8, -5.5 and -59.8% (p = 0.002), 28.1, 1.8 and -70.8%
      for CYFRA21-1 (p = 0.001), and 17.5, -3.1 and -16.9% for NSE, respectively (p =
      0.03). The median TTP for all patients was 6.7 months, while the median TTP for
      CEA decrease and CEA elevated or stable patients was 9.2 and 4.3 months,
      respectively (p < 0.001). Radiologic and CYFRA21-1 responses were significant
      predictive factors for TTP on multivariate analysis (p < 0.001 and p = 0.003,
      respectively). The median OS was 19.2 months for all patients, with a 1-year
      survival rate of 69.4%. Baseline CEA, baseline CYFRA21-1 and CEA response were
      significant predictive factors for OS on multivariate analysis (P = 0.004, P =
      0.004 AND P < 0.001, respectively). CONCLUSION: CEA, CYFRA21-1 and NSE can be
      used in evaluating chemotherapy response, and CYFRA21-1 response was a
      significant predictive factor for TTP, while baseline CEA, baseline CYFRA21-1 and
      CEA response were significant predictive factors for OS in Chinese patients with
      advanced NSCLC.

PMID- 21079401
TI  - Overexpression of MAC30 in the cytoplasm of oral squamous cell carcinoma predicts
      nodal metastasis and poor differentiation.
AB  - BACKGROUND: Expression of the meningioma-associated protein (MAC30) was increased
      in several types of tumors, including esophageal, gastric and colon tumors,
      compared to normal tissue. MAC30 expression levels gradually increased from
      normal colorectal mucosa to primary colorectal cancer and colorectal cancer
      spreading to the lymph nodes. MAC30 expression was related to survival in
      patients with colorectal cancer. However, there is no study on MAC30 in oral
      squamous cell carcinoma (OSCC). METHODS: Therefore, MAC30 expression in OSCC was
      investigated and possible associations of MAC30 expression with
      clinicopathological variables in OSCC have been analyzed. MAC30 expression was
      immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens.
      RESULTS: Expression levels of MAC30 in the cytoplasm markedly increased from
      normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was
      significantly higher in primary OSCC compared to normal oral mucosa samples (51
      vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of
      patients with lymph node metastasis exceeded levels in those without metastasis
      (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was
      higher than in well-differentiated ones (90 vs. 39%, p = 0.005). CONCLUSION:
      Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and
      poor differentiation.

PMID- 21079402
TI  - Bisphosphonates in calcific aortic stenosis: association with slower progression
      in mild disease--a pilot retrospective study.
AB  - OBJECTIVES: An association between aortic valve calcification and osteoporosis
      has been observed. The aim of this study was to assess the association between
      bisphosphonate treatment for osteoporosis and the progression of calcific aortic
      stenosis (AS). METHODS: A retrospective study of patients with AS (mean gradient
      >=10 mm Hg), preserved renal function and two echocardiographies >8 months apart
      was performed. The patients were divided into those treated with bisphosphonates
      for osteoporosis and those not treated and then subdivided into mild (mean
      gradient <30 mm Hg) and moderate-to-severe AS groups. We compared the annualized
      gradient change between the groups and identified predictors of AS progression.
      RESULTS: We analyzed the outcomes of 103 patients (51% females, age 68 +/- 10
      years, follow-up 29 +/- 13 months), of whom 57 had mild and 46 moderate-to-severe
      AS. Bisphosphonates were taken by 28 patients, of whom 22 had mild and 6 moderate
      to-severe AS. In the patients with mild AS, the annualized mean gradient change
      was lower in the bisphosphonate-treated than in the untreated patients (0.1 +/-
      3.3 vs. 2.8 +/- 3.3 mm Hg/year; p = 0.002) and was negatively associated with
      bisphosphonate treatment (beta coefficient -2.36%, 95% confidence interval -4.47
      to -0.26; p = 0.028) independent of age, gender and baseline gradient.
      CONCLUSION: Bisphosphonate treatment was independently associated with slower
      progression of mild AS in patients with preserved renal function.

PMID- 21079403
TI  - A pilot study comparing jejunal pouch and jejunal interposition reconstruction
      after proximal gastrectomy.
AB  - BACKGROUND/AIMS: The incidence of proximal gastric cancer is increasing, so
      proximal gastrectomies are often performed to preserve gastric function, but the
      optimal reconstruction method after surgery remains controversial. We therefore
      conducted a prospective pilot study comparing reconstructions using jejunal pouch
      interposition or jejunal interposition. METHODS: Thirty-eight patients with early
      proximal gastric cancer were included in this study. Equal numbers of patients
      were randomly assigned for reconstruction using jejunal interposition (the IP
      group) or jejunal pouch interposition (the PO group). Postoperative morbidity and
      patient symptoms were compared between the 2 groups. RESULTS: Postoperative
      morbidity was significantly more frequent in the IP than the PO group (p =
      0.036). Moreover, the incidence of gastrointestinal complaints was more frequent
      in the IP group until 6 months after surgery. By contrast, the caloric intake was
      more favorable in the PO group until 1 year post-surgery. CONCLUSION: Short-term
      and mid-term outcomes were more favorable following jejunal pouch interposition
      compared with jejunal interposition after proximal gastrectomy.

PMID- 21079404
TI  - Stroke characteristics in patients with pretreated arterial hypertension.
AB  - BACKGROUND: Arterial hypertension (AH) is one of the most important vascular risk
      factors for stroke that can be treated. The present retrospective study analyses
      the influence of pretreated AH on the outcome of patients with ischaemic and
      haemorrhagic strokes, compared to those with normal blood pressure (BP). PATIENTS
      AND METHODS: The demographic features, vascular risk factors, stroke type, stroke
      severity (according to the National Institutes of Health Stroke scale) and
      disability (according to the modified Rankin scale) were compared between 806
      pretreated hypertensive patients and 320 ones with normal BP. RESULTS: The
      incidence and the severity of the ischaemic strokes were similar but the outcome
      was worse in patients with pretreated AH compared to those with normal BP. In the
      former patients, coronary artery disease and isolated atrial fibrillation were
      found as confounders on multivariate analysis. The incidence, the severity and
      the outcome of patients with a haemorrhagic stroke were similar in both groups.
      CONCLUSIONS: The outcome in ischaemic stroke is worse in pretreated AH patients,
      compared to normotensive ones, probably due to the higher incidence of other
      associated vascular risk factors. Pretreated AH improves the outcome of patients
      with a haemorrhagic stroke.

PMID- 21079405
TI  - Hot cross bun anyone?

PMID- 21079407
TI  - Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated
      patients with recurrent ovarian cancer.
AB  - AIM: To retrospectively assess the efficacy and safety of bevacizumab plus low
      dose metronomic oral cyclophosphamide in heavily pretreated patients with
      recurrent ovarian cancer. PATIENTS AND METHODS: Patients with recurrent ovarian
      cancer and prior treatment with platinum- and taxane-based chemotherapy were
      included. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks
      plus oral cyclophosphamide 50 mg daily until disease progression or unacceptable
      toxicity. Response rates (RR) were determined according to RECIST criteria and by
      monitoring the CA 125 serum tumor marker according to Rustin's criteria. The
      endpoints were progression-free survival (PFS), RR, overall survival (OS), and
      safety. RESULTS: Thirty-eight patients were treated; 79% were platinum resistant
      and 21% were platinum sensitive. The median number of previous treatments was 4
      (range 1-8). Seventy-nine percent of patients had received more than 2 previous
      lines of treatment. Eighty-one percent of patients had received gemcitabine, 76%
      liposomal doxorubicin, and 50% topotecan. A median of 8 (range 1-70) cycles of
      bevacizumab were administered. The overall RR was a complete response (CR) in 3
      patients (8.1%), a partial response (PR) in 12 (32.4%), and stable disease (SD)
      >=6 months in 3 (8.1%). The median PFS and OS were 4.5 and 10.7 months,
      respectively. Thirty-nine percent of patients were progression free for at least
      6 months. In an exploratory analysis there was a significant relation of prior
      platinum response and performance status with the risk of progression. Grade 3-4
      toxicities included anemia (1), hypertension (2), hematuria (1), arterial
      thrombosis in the leg (1), dyspnea (1), and intestinal fistulae (1). There were
      no cases of gastrointestinal perforation (GIP) or treatment-related deaths.
      CONCLUSION: The combination of bevacizumab and metronomic cyclophosphamide was
      active and well-tolerated in heavily pretreated patients with recurrent ovarian
      cancer.

PMID- 21079406
TI  - Equivalence of pegfilgrastim and filgrastim in lymphoma patients treated with
      BEAM followed by autologous stem cell transplantation.
AB  - OBJECTIVE: To evaluate the impact of pegfilgrastim on engraftment, hospital stay
      and resources in patients with Hodgkin's and non-Hodgkin's lymphoma after
      conditioning with high-dose BEAM followed by autologous peripheral blood stem
      cell transplantation (APBSCT) compared with filgrastim. METHODS: We reviewed
      patient charts and our prospective transplantation database for clinical data
      from the post-transplant period. An integrated cost analysis, including the use
      of blood products and length of hospital stay, was also performed. RESULTS:
      Fourteen (26%) patients with Hodgkin's lymphoma and 40 (74%) patients with non
      Hodgkin's lymphoma were analyzed. Thirty-four (68%) patients received single-dose
      pegfilgrastim (6 mg), and 20 (32%) patients received daily filgrastim (5 MUg/kg)
      after APBSCT. No differences were observed regarding duration of neutropenia
      grade 4 (pegfilgrastim median 7 days/filgrastim median 8 days; p = 0.13),
      thrombocytopenia grade 4 (7/9.5 days, respectively; p = 0.21), fever (4.5/2 days;
      p = 0.057), intravenous antibiotic treatment (11/10 days; p = 0.75) or length of
      hospital stay (16.5/16 days; p = 0.27) between the groups. The use of
      pegfilgrastim resulted in 12% higher treatment-related costs when compared to
      filgrastim, without reaching statistical significance (p = 0.38). CONCLUSION:
      Pegfilgrastim appears to be equivalent to filgrastim after high-dose BEAM
      followed by APBSCT in the treatment of lymphoma patients.

PMID- 21079409
TI  - Associations between gender, ocular parameters and diseases: the Beijing Eye
      study.
AB  - BACKGROUND: To assess relationships between gender, ocular parameters and ocular
      diseases. METHODS: The Beijing Eye Study is a population-based study including
      4,439 Chinese. All participants underwent a detailed ophthalmic examination,
      anthropometric measurements and analytic blood examinations. RESULTS: In
      multivariate regression analysis, female gender was significantly associated with
      a shallower anterior chamber (p < 0.001) and narrower anterior chamber angle (p =
      0.001), higher prevalence of dry eye (p = 0.002), lower best-corrected visual
      acuity (p = 0.04) and lower presenting visual acuity (p = 0.046), and with the
      systemic parameters of lower educational level (p < 0.001), rural region (p =
      0.002), lower frequency of smoking (p < 0.001) and alcohol consumption (p <
      0.001), lower body height (p < 0.001), lower diastolic blood pressure (p < 0.001)
      and higher systolic blood pressure (p < 0.001), and higher serum concentrations
      of triglycerides (p = 0.005), low-density lipoproteins (p < 0.001) and high
      density lipoproteins (p < 0.001). Men and women did not vary significantly in
      refractive error, intraocular pressure, central corneal thickness, size of the
      optic disk and parapapillary atrophy, and prevalences of retinal microvascular
      abnormalities, trachoma, pterygia, nuclear cataract, posterior subcapsular or
      cortical cataract, angle-closure glaucoma, open-angle glaucoma, age-related
      macular degeneration and retinal vein occlusions. CONCLUSIONS: After controlling
      for systemic factors, females have a shallower anterior chamber, a narrower
      anterior chamber angle and a higher prevalence of dry eye.

PMID- 21079408
TI  - Toll-like receptor 3 polymorphism rs3775291 is not associated with choroidal
      neovascularization or polypoidal choroidal vasculopathy in Chinese subjects.
AB  - BACKGROUND/AIMS: Age-related macular degeneration (AMD) is a leading cause of
      visual impairment. A single-nucleotide polymorphism (SNP; rs3775291) in the Toll
      like receptor 3 (TLR3) gene has recently been implicated in the pathogenesis of
      AMD in Caucasian populations. The aim of this study was to examine this
      association in Chinese persons with choroidal neovascularization (CNV) secondary
      to AMD and polypoidal choroidal vasculopathy (PCV). METHODS: This was an
      observational cross-sectional study in Singapore. Study subjects were of Chinese
      ethnicity and included patients with exudative maculopathy and normal control
      subjects. The diagnoses of CNV and PCV were made based on fundus examination,
      fluorescein angiography and indocyanine green angiography findings. Genomic DNA
      was extracted, and genotypes were determined by bidirectional DNA sequencing. We
      compared the allele and genotype frequencies between subjects with CNV and PCV
      with controls using the software PLINK. RESULTS: A total of 246 subjects with
      exudative maculopathy (consisting of 126 with CNV and 120 with PCV) and 274
      normal control subjects were recruited. The distribution of rs3775291 SNP
      genotypes for CNV and PCV was not significantly different from that for normal
      controls. CONCLUSION: This study indicates that the TLR3 rs3775291 gene
      polymorphism is not associated with CNV and PCV in Singaporean Chinese patients.

PMID- 21079410
TI  - Initial visual acuity is an important prognostic factor in patients with branch
      retinal vein occlusion.
AB  - PURPOSE: To evaluate the role of initial visual acuity (VA) as a potential
      prognostic factor for final VA in patients with branch retinal vein occlusion
      (BRVO). METHODS: A retrospective data analysis involving 163 patients with
      macular edema secondary to BRVO treated according to the recommendations of the
      Branch Vein Occlusion Study Group was performed using univariate and multivariate
      logistic regression models, and receiver-operating characteristics analysis. The
      analyses take factors into account that can potentially influence final visual
      result: sex, age, type of occlusion (major temporal or macular), grid
      photocoagulation and ischemia. RESULTS: The final VA <= 0.1 was statistically
      significantly related to initial VA <= 0.16 and age > 70 years. Sex, type of
      occlusion, grid photocoagulation and ischemia did not significantly influence the
      prediction of final VA based on age and initial VA. CONCLUSIONS: The analysis
      shows that initial VA and age > 70 years significantly influence the prognosis
      for final visual results in patients with BRVO.

PMID- 21079411
TI  - Long-term treatment with macrolides - light in the darkness of COPD therapy?

PMID- 21079412
TI  - Fatal cerebral air embolism following uneventful flexible bronchoscopy.
AB  - Flexible bronchoscopy is a widely used and safe procedure with a reported maximal
      mortality rate of 0.04% and a major-complications rate of 0.5%. There are,
      however, only few case descriptions for postinterventional cerebral air embolism
      and the frequency of this supposedly rare complication is unknown. The current
      study presents 2 patients with non-small cell lung cancer who suffered fatal
      cerebral air embolism following diagnostic bronchoscopy with transbronchial
      needle aspiration and transbronchial biopsy, resulting in a frequency of <0.02%
      for this severe complication in our institution. In addition to early supportive
      measures, 1 patient received hyperbaric oxygen therapy as further treatment.
      Prompt recognition of this complication is mandatory in order to implement
      appropriate supportive measures. High-flow oxygen should be administered and
      hyperbaric oxygen therapy may be considered, if available. If possible, positive
      pressure ventilation should be avoided.

PMID- 21079413
TI  - Selective removal of dishevelled by autophagy: a role of p62.

PMID- 21079414
TI  - The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited
      independently to bacteria-associated microdomains to target Salmonella to the
      autophagy pathway.
AB  - Autophagy is an innate immune defense against bacterial invasion. Recent studies
      show that two adaptor proteins, p62 and NDP52, are required for autophagy of the
      bacterial pathogen Salmonella enterica serovar Typhimurium (S. typhimurium).
      However, it is not known why two different adaptors are required to target the
      same bacterial cargo to autophagy. Here we show that both adaptors are recruited
      to bacteria with similar kinetics, that they are recruited to bacteria
      independently of each other, and that depletion of either adaptor leads to
      impairment of antibacterial autophagy. Depletion of both adaptors does not
      synergistically impair autophagy, indicating they act in the same pathway.
      Remarkably, we observed that these adaptors do not colocalize, but rather form
      non-overlapping microdomains surrounding bacteria. We conclude that p62 and NDP52
      act cooperatively to drive efficient antibacterial autophagy by targeting the
      protein complexes they coordinate to distinct micro-domains associated with
      bacteria.

PMID- 21079415
TI  - Unleashing the Ambra1-Beclin 1 complex from dynein chains: Ulk1 sets Ambra1 free
      to induce autophagy.
AB  - The Beclin 1-VPS34 complex plays a crucial role in the induction of the
      autophagic process by generating PtdIns(3)P-rich membranes, which act as
      platforms for ATG protein recruitment and autophagosome nucleation. Several
      cofactors, such as Ambra1, ATG14 and UVRAG, are necessary for Beclin 1 complex
      activity. However, the mechanism by which Beclin 1 complex activity is:
      stimulated by autophagic stimuli has not yet been fully elucidated. Recently, we
      reported that autophagosome formation in mammalian cells is primed by Ambra1
      release from the dynein motor complex. We found that Ambra1 specifically binds
      the dynein motor complex under normal conditions through a direct interaction
      with DLC1. When autophagy is induced, Ambra1-DLC1 are released from the dynein
      complex in an ULK1-dependent manner, and relocalize to the endoplasmic reticulum,
      thus enabling autophagosome nucleation. In addition, we found that both DLC1
      downregulation and Ambra1 mutations in its DLC1-binding sites strongly enhance
      autophagosome formation. Ambra1 is therefore not only a cofactor of Beclin 1 in
      favoring its kinase-associated activity, but also a crucial upstream regulator of
      autophagy initiation.

PMID- 21079416
TI  - Erratum to: Huang Q, Shen H-M. To die or to live: the dual role of poly(ADP
      ribose) polymerase-1 in autophagy and necrosis under oxidative stress and DNA
      damage. Autophagy 2009; 5:273-6.

PMID- 21079417
TI  - A role for diacylglycerol in antibacterial autophagy.

PMID- 21079418
TI  - The fellowship of the ring.

PMID- 21079420
TI  - Minocycline inhibits the growth of glioma by inducing autophagy.
AB  - Minocycline has been shown to alleviate several neurological disorders.
      Unexpectedly, we found that minocycline had opposite effects on glioma cells:
      minocycline induced nonapoptotic cell death in glioma cells. The glioma cell
      death was associated with the presence of autophagic vacuoles in the cytoplasm.
      Minocycline induced autophagy was confirmed by acridine orange,
      monodansylcadaverine (MDC) stainings of vesicle formation and the conversion of
      microtubule-associated proteins light chain 3 (LC3-I) to LC3-II. Pretreatment
      with autophagy inhibitor 3-methyladenine (3-MA) suppressed the induction of
      acidic vesicular organelles and the accumulation of LC3-II to the autophagosome
      membrane in glioma cells treated with minocycline. Despite the pretreatment of 3
      MA, minocycline induced cell death which could result from the activation of
      caspase-3. Minocycline effectively inhibited tumor growth and induced autophagy
      in the xenograft tumor model of C6 glioma cells. These results suggest that
      minocycline may kill glioma cells by inducing autophagic cell death. When
      autophagy was inhibited, minocycline still induced cell death through the
      activation of caspase-3. Thus, minocycline is a promising agent in the treatment
      of malignant gliomas.

PMID- 21079421
TI  - Gene expression profiles of human osteosarcoma cell sublines with different
      pulmonary metastatic potentials.
AB  - AIM: to screen the pulmonary metastasis-associated molecules of Osteosarcoma and
      evaluate their functions concerning prognosis prediction. METHODS: cDNA
      microarray analysis has been applied to 2 pairs of osteosarcoma cell sublines
      with differential metastatic potentials to the lung. Immunohistochemistry and
      survival analysis have been performed to clinical samples of osteosarcoma
      patients. RESULT: Analysis detected 484 differentially expressed genes between
      the high metastatic subline, F5M2, and the low metastatic subline, F4. There were
      1257 genes differentially expressed between newly established high-metastatic
      sublines named Saos-2M2 and its parental cell line Saos-2. Furthermore, 16
      commonly up-regulated genes and 5 commonly down-regulated genes were identified
      by clustering analysis. EREG and CHST2, two genes not previously described in
      osteosarcoma, were finally seen to be differentially expressed in all examined
      osteosarcoma cell lines and in samples between the different prognosis sample
      groups. Survival analysis also confirmed these two molecules could be used to
      predict the outcome of OSA patients. CONCLUSION: This work represents a rationale
      approach to the evaluation of microarray data and will be useful to identify
      genes that may be causally associated with metastasis. EREG and CHST2 will be
      likely considered as clinical molecular markers to predict the outcome of OSA.

PMID- 21079422
TI  - Isoniazid preventive therapy for HIV-infected people: evidence to support
      implementation.

PMID- 21079419
TI  - Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors.
AB  - Vascular endothelial growth factor (VEGF) A is a major promoter of tumor
      angiogenesis and a prime target of antiangiogenic cancer therapy. To examine
      whether endothelial cell signaling might provide histological biomarkers of
      angiogenesis and VEGF activity in vivo, normal mouse organs and multiple tumor
      models were studied immunohistochemically for endothelial expression of activated
      ERK, STAT3, and AKT. Phospho(p)-ERK and p-STAT3 expression was negligible in the
      endothelia of normal organs but was significantly elevated in tumor endothelium.
      p-AKT was present at significant and comparable levels in both tumor and normal
      endothelia. In K1735 tumors induced to express more VEGF, endothelial p-ERK, p
      STAT3 and p-AKT increased accompanied by signs of accelerated angiogenesis.
      Treatment of K1735 and Colo-205 tumors with the VEGF inhibitor, VEGF Trap
      (aflibercept), decreased tumor endothelial p-ERK, p-STAT3 and p-AKT expression
      accompanied by signs of antiangiogenic effect. These results show that
      endothelial p-ERK and p-STAT3 (but not p-AKT) distinguish tumor from normal
      vessels and that the presence of these two signaling intermediates may be useful
      indicators of tumor angiogenic activity and angiogenesis inhibition by VEGF
      antagonist.

PMID- 21079423
TI  - Why have trials of isoniazid preventive therapy among people with HIV infection
      not demonstrated an effect on mortality?: did close examination of the trees
      obscure our view of the wood?

PMID- 21079424
TI  - Symptom and chest radiographic screening for infectious tuberculosis prior to
      starting isoniazid preventive therapy: yield and proportion missed at screening.
AB  - OBJECTIVE: This analysis describes the prevalence of and risk factors for
      tuberculosis at screening prior to isoniazid preventive therapy (IPT); the
      additional yield of tuberculosis using chest radiography versus symptoms alone,
      and risk factors for tuberculosis missed by screening. DESIGN: Cross-sectional
      analysis of a trial of community-wide IPT in South African gold mines. METHODS:
      Participants were screened for tuberculosis prior to starting IPT using symptoms
      (cough >2 weeks, weight loss, night sweats) and chest radiography. Tuberculosis
      suspects had sputum collected for mycobacterial investigations. Those with a
      positive smear or culture with no speciation or culture identified as
      Mycobacterium tuberculosis were classified as having probable or definite
      tuberculosis, respectively. Among participants who were dispensed IPT, we defined
      a 'missed' case of active tuberculosis as one identified within 90 days of the
      enrolment screen. RESULTS: Between July 2006 and December 2008, among 23,286
      participants with complete data, the prevalence of undiagnosed tuberculosis
      [definite (284) and probable (31)] was high (315/23 286; 1.4%). The addition of
      chest radiography to symptom screening increased the number of definite
      tuberculosis cases detected by 2.5-fold (113 to 281 cases). Among 19,609
      individuals correctly screened for tuberculosis who started IPT and had more than
      90 days of follow-up, only 39 (0.2%) active tuberculosis cases were missed. Risk
      factors for tuberculosis missed by screening included increasing age [adjusted
      odds ratio (aOR) 1.66/10 year increase, 95% confidence interval (CI) 1.07-2.56],
      non-South African, in HIV care (aOR 4.80, 95% CI 1.63-14.1), lower weight (aOR
      2.07/10 kg decrease, 95% CI 1.23-3.49) and alcohol use (aOR 2.52, 95% CI 1.31
      4.86), which were similar to risk factors for tuberculosis detected by screening.
      CONCLUSION: Tuberculosis screening prior to IPT detects a substantial burden of
      tuberculosis and misses very few cases. Chest radiography significantly increased
      the yield of tuberculosis cases detected.

PMID- 21079426
TI  - 'Team up against TB': promoting involvement in Thibela TB, a trial of community
      wide tuberculosis preventive therapy.
AB  - OBJECTIVE: To describe a programme of community education and mobilization to
      promote uptake in a cluster-randomized trial of tuberculosis preventive therapy
      offered to all members of intervention clusters. SETTING AND PARTICIPANTS: Gold
      mines in South Africa, where tuberculosis incidence is extremely high, despite
      conventional control measures. All employees in intervention clusters (mine shaft
      and associated hostel) were invited to enrol. MAIN OUTCOME MEASURE: Cumulative
      enrolment in the study in intervention clusters. RESULTS: Key steps in
      communicating information relevant to the study included extensive consultation
      with key stakeholders; working with a communication company to develop a project
      'brand'; developing a communication strategy tailored to each intervention site;
      and involving actors from a popular television comedy series to help inform
      communities about the study. One-to-one communications used peer educators along
      with study staff, and participant advisory groups facilitated two-way
      communication between study staff and participants. By contrast, treatment
      'buddies' and text messaging to promote adherence proved less successful. Mean
      cumulative enrolment in the first four intervention clusters was 61.9%,
      increasing to 83.0% in the final four clusters. CONCLUSION: A tailored
      communication strategy can facilitate a high level of enrolment in a community
      health intervention.

PMID- 21079425
TI  - Adverse events with isoniazid preventive therapy: experience from a large trial.
AB  - OBJECTIVES: We describe isoniazid-related adverse events in Thibela TB, a cluster
      randomized study of community-wide isoniazid preventive therapy (IPT) among gold
      miners in South Africa, where HIV prevalence is estimated at 30%. METHODS:
      Consenting employees were screened prior to IPT for active tuberculosis and
      increased risk of isoniazid toxicity using a questionnaire and chest radiograph.
      Study-defined IPT-related adverse events were sought at each study visit: liver
      function tests were only performed if clinically indicated. In a substudy, we
      questioned consecutive participants at baseline and months 1, 3, and 6 concerning
      minor IPT-related adverse events. RESULTS: Among 24,221 participants (95.2% men,
      median age 40 years), 130 individuals had 132 study-defined adverse events
      (0.54%); 61 (0.25%) possible hypersensitivity rash, 50 (0.21%) peripheral
      neuropathy, 17 (0.07%) clinical hepatotoxicity, and four (0.02%) convulsions.
      Four events (two hepatotoxicity, one fatal, and two convulsions) fulfilled
      criteria for seriousness. Clinical hepatotoxicity was associated with consumption
      of alcohol [0.11 vs. 0.03% if no alcohol consumed, odds ratio 3.9 (95% confidence
      interval 1.2-12.1)], but not with sex, age, weight, or concurrent antiretroviral
      therapy. In the substudy, 324 of 498 (65.1%) participants reported better health
      since starting IPT; 180 of 324 (55.6%) reported that this was because of
      increased appetite. The frequency of specific minor symptoms was low among those
      taking IPT, and all symptoms were reported less often than at baseline.
      CONCLUSION: The risk of adverse events, particularly hepatotoxicity, was very low
      in this population. Our data suggest that clinical criteria can safely be used
      for screening prior to and monitoring during IPT.

PMID- 21079427
TI  - Barriers to implementation of isoniazid preventive therapy in HIV clinics: a
      qualitative study.
AB  - OBJECTIVES: Despite good evidence that isoniazid preventive therapy (IPT) reduces
      incidence of tuberculosis among people with HIV infection, implementation of IPT
      is low. This study aimed to describe barriers to IPT implementation from
      healthcare provider and patient perspectives in a donor-funded HIV care programme
      in Gauteng province, South Africa, in which IPT is recommended, but delivery is
      variable. DESIGN: A qualitative study using in-depth interviews and a focus group
      discussion. METHODS: We conducted interviews with 22 clinic staff and 20 patients
      from 10 purposively selected HIV clinics, and a staff focus group discussion.
      Staff were questioned on their knowledge and experience of IPT, and asked about
      barriers to its use. Patients were asked for their opinions about taking IPT.
      RESULTS: Healthcare workers reported the primary barrier to IPT use was lack of
      knowledge and experience. Prescribers were unaware of the benefits of IPT and
      unclear about guidelines. The belief that existing screening tools are inaccurate
      in HIV-infected individuals and the need to refer patients to separate clinics
      for tuberculosis screening also emerged as barriers. No patients had heard of
      IPT. CONCLUSION: Barriers to the widespread use of IPT primarily derived from
      healthcare workers, in particular, lack of experience among physicians. In
      addition to overcoming operational barriers, a change in healthcare worker
      perception is needed if IPT is to be widely used; we suggest local clinical
      opinion leaders could help achieve this.

PMID- 21079428
TI  - The implementation of isoniazid preventive therapy in HIV clinics: the experience
      from the TB/HIV in Rio (THRio) study.
AB  - OBJECTIVE: The TB/HIV in Rio (THRio) study was launched in September 2005 to
      assess the impact of integrated tuberculosis (TB) and HIV treatment strategies in
      29 HIV clinics in Rio de Janeiro, Brazil. DESIGN: THRio is a cluster-randomized
      trial (CRT) to determine whether routine screening for and treatment of latent TB
      in HIV clinic patients with access to antiretroviral therapy will reduce TB
      incidence at the clinic level. THRio is part of the Consortium to Respond
      Effectively to AIDS/TB Epidemic that is implementing research studies to assess
      the impact of bold, new public health paradigms for controlling the AIDS/TB
      epidemic. METHODS: Twenty-nine public primary HIV clinics were randomly assigned
      a date to begin implementing TB screening procedures and provision of isoniazid
      preventive therapy (IPT) for TB/HIV coinfected patients. Final analysis of the
      CRT is expected in 2011. RESULTS: Starting at date of tuberculin skin test
      (TST)/IPT implementation at each clinic through August 2010, 1670 HIV-infected
      patients initiated IPT, of which 215 are still receiving treatment. Of the
      remaining 1455 patients, 1230 (85%) completed therapy and only 20 (1.2%) patients
      initiating IPT reported adverse reactions leading to discontinuation of therapy.
      IPT completion was higher among HIV-infected patients receiving HAART (87%) than
      those not yet receiving HAART (79%, P < 0.01). Times to TST and IPT have markedly
      decreased postintervention, but remain considerably long. The richness of the
      THRio database has resulted in several analyses of this expansive cohort of HIV
      infected patients that are reviewed here. CONCLUSIONS: The national
      implementation of TST and IPT for HIV-positive patients in Brazil has been
      invigorated partly due to THRio's baseline results. Expanded use of IPT in HIV
      patients in Rio de Janeiro is achievable with high adherence and low adverse
      events, although this effort requires a package of activities including training,
      advocacy and reorganization of services.

PMID- 21079430
TI  - Implementation of isoniazid preventive therapy for people living with HIV
      worldwide: barriers and solutions.

PMID- 21079429
TI  - Association of isoniazid preventive therapy with lower early mortality in
      individuals on antiretroviral therapy in a workplace programme.
AB  - OBJECTIVE: To describe the association between isoniazid preventive therapy (IPT)
      and mortality among individuals starting antiretroviral therapy (ART) in a
      workplace programme in South Africa where tuberculosis (TB) incidence is very
      high. METHODS: ART-naive individuals starting ART from January 2004 to December
      2007 were followed for up to 12 months. Deaths were ascertained from clinic and
      human resource data. The association between IPT and mortality was assessed using
      Cox regression. RESULTS: A total of 3270 individuals were included (median age
      45; 93% men; median baseline CD4 cell count 155 cells/MUl (interquartile range 87
      221); and 45% with WHO stage 3/4]. Nine hundred twenty-two (28%) individuals
      started IPT either prior to or within 3 months of starting ART. Individuals who
      started IPT tended to have less advanced HIV disease at ART initiation. Two
      hundred fifty-nine (7.9%) deaths were observed with overall mortality rate 8.9
      per 100 person-years [95% confidence interval (CI) 7.9-10.6]. The unadjusted
      mortality rate was lower among those who received IPT compared with those who did
      not [3.7/100 vs. 11.1/100 person-years, respectively, hazard ratio 0.34 (95% CI
      0.24-0.49)]; this association remained after adjustment for age, baseline CD4
      cell count, baseline WHO stage, year of ART start, and individual company (hazard
      ratio 0.51, 95% CI 0.32-0.80). In sensitivity analyses restricted to those with
      no previous history of TB (n = 3036) or with no TB symptoms at ART initiation (n
      = 2251), IPT remained associated with reduced mortality [adjusted hazard ratios
      0.51 (95% CI 0.32-0.81) and 0.48 (95% CI 0.24-0.96), respectively]. CONCLUSION:
      Mortality was lower among individuals receiving IPT with or prior to ART start.
      These results support routine use of IPT in conjunction with ART.

PMID- 21079431
TI  - Sport injury prevention: time for an intervention?

PMID- 21079432
TI  - Decision making processes in sports and in medicine: refereeing the game.

PMID- 21079433
TI  - Apolipoprotein E genotyping and concussion: time to fish or cut bait.

PMID- 21079434
TI  - The prevention of sport injury: an analysis of 12,000 published manuscripts.
AB  - OBJECTIVE: To identify the nature and extent of research in sport injury
      prevention with respect to 3 main categories: (1) training, (2) equipment, and
      (3) rules and regulations. DATA SOURCES: We searched PubMed, CINAHL, Web of
      Science, Embase, and SPORTDiscus to retrieve all sports injury prevention
      publications. Articles were categorized according to the translating research
      into injury prevention practice model. RESULTS: We retrieved 11 859 articles
      published since 1938. Fifty-six percent (n = 6641) of publications were
      nonresearch (review articles and editorials). Publications documenting incidence
      (n = 1354) and etiology (n = 2558) were the most common original research
      articles (33% of total). Articles reporting preventive measures (n = 708) and
      efficacy (n = 460) were less common (10% of the total), and those investigating
      implementation (n = 162) and effectiveness (n = 32) were rare (1% of total). Six
      hundred seventy-seven studies focused on equipment and devices to protect against
      injury, whereas 551 investigated various forms of physical training related to
      injury prevention. Surprisingly, publications studying changes in rules and
      regulations aimed at increasing safety and reducing injuries were rare (<1%; n =
      63) with a peak of only 20 articles over the most recent 5-year period and an
      average of 10 articles over the preceding 5-year blocks of time. CONCLUSIONS:
      Only 492 of 11 859 publications actually assessed the effectiveness of sports
      injury prevention interventions or their implementation. Research in the area of
      regulatory change is underrepresented and might represent one of the greatest
      opportunities to prevent injury.

PMID- 21079435
TI  - Normative spleen size in tall healthy athletes: implications for safe return to
      contact sports after infectious mononucleosis.
AB  - OBJECTIVE: To establish normative parameters of the spleen by ultrasonography in
      tall athletes. DESIGN: Prospective cohort observational study. SETTING:
      University of Buffalo, Erie County Community College, University of Texas at
      Tyler, and Austin College. PARTICIPANTS: Sixty-six athletes enrolled and finished
      the study. Height requirements were at least 6 feet 2 inches for men and at least
      5 feet 7 inches in women. INTERVENTIONS: Measurement of spleen size in tall
      athletes. MAIN OUTCOME MEASURES: Ultrasound measurements of spleen size in tall
      athletes were compared with "normal-sized" controls from the literature. Mean,
      SD, and variance determined the sample distribution, and a one sample t test
      compared measurements in tall athletes with historical measurements in the
      average height population. Statistical significance was defined as P < 0.05.
      RESULTS: Mean height was 192.26 cm (SD, +/- 6.52) for men and 176.54 cm (SD, +/-
      5.19) for women. Mean splenic measurements for all subjects were 12.19 cm (SD, +/
      1.45) for spleen length, 8.88 cm (SD, +/- 0.96) for spleen width, and 5.55 cm
      (SD, +/- 0.76) for spleen thickness. The study mean for spleen length was 12.192
      cm (95% confidence interval, 11.835-12.549) and population mean was 8.94 cm (2
      tailed t test, P < 0.01). In this population of tall athletes, normal spleen size
      was significantly larger than the normal spleen size of an average individual.
      CONCLUSIONS: In the clinical arena, it can be difficult to know when the tall
      athletes with splenomegaly from infectious mononucleosis can safely return to
      contact sports. Previously, there has not been a sufficient "norm" for this
      population, but this study helps to establish baseline values.

PMID- 21079436
TI  - The effect of kinesiotape on function, pain, and motoneuronal excitability in
      healthy people and people with Achilles tendinopathy.
AB  - OBJECTIVE: To investigate the effect of kinesiotape on hop distance, pain, and
      motoneuronal excitability in healthy people and people with Achilles tendinopathy
      (AT). DESIGN: Within-subject design. SETTING: An academic health science center,
      which is an acute London National Health Service trust. PARTICIPANTS: With
      ethical approval and informed consent, a convenience sample of 26 healthy people
      and 29 people with AT were recruited. Seven participants were lost after
      functional testing, leaving 24 participants in each group. INTERVENTIONS:
      Kinesiotape applied over the Achilles tendon. MAIN OUTCOME MEASURES: The single
      leg hop test and visual analog scale were measured with and without the tape.
      Using the Hoffman (H) reflex, change in motoneuronal excitability of calf muscles
      was measured before tape application, with the tape on and after its removal.
      RESULTS: There were no changes to hop distance when tape was applied (P = 0.55).
      Additionally, there were no changes to pain (P = 0.74). The H reflex amplitude of
      soleus and gastrocnemius increased in the healthy group after its removal (P =
      0.01 and P = 0.03, respectively), whereas the H reflex remained unchanged in
      people with AT (P = 0.43 and 0.16, respectively). CONCLUSIONS: Calf muscles were
      facilitated by kinesiotape in healthy participants. Despite this, there was no
      change to hop distance. Kinesiotape had no effect on hop distance, pain, or
      motoneuronal excitability in people with AT. These results do not support the use
      of kinesiotape applied in this way for this condition.

PMID- 21079437
TI  - Analysis of the ability of catcher's masks to attenuate head accelerations on
      impact with a baseball.
AB  - OBJECTIVE: The goals of this study were to measure the ability of catcher's masks
      to attenuate head accelerations on impact with a baseball and to compare these
      head accelerations to established injury thresholds for mild traumatic brain
      injury. DESIGN: Testing involved using a pneumatic cannon to shoot baseballs at
      an instrumented Hybrid III headform (a 50th percentile male head and neck) with
      and without a catcher's mask on the head. The ball speed was controlled from
      approximately 26.8 to 35.8 m/s (60-80 mph), and the regulation National
      Collegiate Athletic Association baseballs were used. SETTING: Research
      laboratory. PATIENTS: None. INDEPENDENT VARIABLES: Catcher's masks and impact
      velocity. MAIN OUTCOME MEASURES: The linear and angular head accelerations of the
      Hybrid III headform. RESULTS: Peak linear resultant acceleration was 140 to 180 g
      without a mask and 16 to 30 g with a mask over the range of ball's speed
      investigated. Peak angular resultant acceleration was 19 500 to 25 700 rad/s
      without a mask and 2250 to 3230 rad/s with a mask. The Head Injury Criterion was
      93 to 181 without a mask and 3 to 13 with a mask, and the Severity Index was 110
      to 210 without a mask and 3 to 15 with a mask. CONCLUSIONS: Catcher's masks
      reduced head acceleration metrics by approximately 85%. Head acceleration metrics
      with a catcher's mask were significantly lower than contemporary injury
      thresholds, yet reports in the mass media clearly indicate that baseball impacts
      to the mask still occasionally result in mild traumatic brain injuries. Further
      research is needed to address this apparent contradiction.

PMID- 21079438
TI  - Comparative biomechanical effectiveness of over-the-counter devices for
      individuals with a flexible flatfoot secondary to forefoot varus.
AB  - OBJECTIVES: Evaluate effects of a new off-the-shelf insert on frontal plane foot
      biomechanics and compare effectiveness of the new and an existing off-the-shelf
      insert and a motion-control shoe in neutralizing frontal plane foot biomechanics.
      DESIGN: Descriptive. SETTING: Biomechanics laboratory. PARTICIPANTS: Fifteen
      uninjured subjects with a flexible flatfoot secondary to forefoot varus.
      ASSESSMENT OF RISK FACTORS: Three-dimensional kinematic and kinetic data were
      collected as subjects walked and jogged at their self-selected speed while
      wearing a motion-control running shoe, the shoe with a new off-the-shelf insert,
      and the shoe with an existing off-the-shelf insert. MAIN OUTCOME MEASURES:
      Frontal plane kinematics and rearfoot kinetics were evaluated during stance.
      Statistical analysis was performed using a repeated measures analysis of variance
      and Student-Newman-Keuls post hoc tests (alpha <= 0.05). RESULTS: The new insert
      and motion-control shoe placed the forefoot in a less-everted position than the
      existing off-the-shelf insert during walking. There were no differences in
      forefoot kinematics during jogging, nor were there differences in rearfoot motion
      during walking or jogging. The rearfoot eversion moment was significantly lower
      with the new off-the-shelf insert compared with the motion-control shoe and the
      existing insert during walking and jogging. CONCLUSIONS: A new off-the-shelf
      device is available that promotes more neutral frontal plane biomechanics, thus
      providing a theoretical rationale for using this device for injury prevention and
      treatment. The comparative biomechanical effectiveness of a motion-control shoe
      and the orthotic inserts may assist health care professionals in selecting a
      device to correct the flatfoot structure.

PMID- 21079439
TI  - Prevalence and characteristics of general and football-specific emergency medical
      service activations by high school and collegiate certified athletic trainers: a
      national study.
AB  - OBJECTIVE: To describe frequency and characteristics of emergency medical
      services (EMS) activations by certified athletic trainers (ATs) and effects of
      pre-season planning meetings on interactions between ATs and EMS both generally
      and specifically during football head/neck emergencies. DESIGN: Retrospective
      cross-sectional survey. SETTING: 2009 Web-based survey. PARTICIPANTS: Athletic
      trainers (n = 1884; participation rate, 28%) in high school and collegiate
      settings. INDEPENDENT VARIABLES: Athletic trainer work setting, AT demographics,
      history of pre-season planning meetings. MAIN OUTCOME MEASURES: Proportions and
      95% confidence intervals (CIs) estimated the prevalence of EMS activation,
      planning meetings, and characteristics of AT-EMS interactions (eg, episodes of AT
      perceived inappropriate care and on-field disagreements). Chi square tests tested
      differences (P < 0.05) in proportions. Associations (odds ratio = OR and 95% CI)
      between work setting, demographics, preseason meetings and fall 2008 1) episodes
      of AT-perceived inappropriate care, and 2) on-field disagreements were assessed
      using multivariate logistic regression. RESULTS: High school ATs activated EMS
      more frequently than collegiate ATs (eg, fall 2008 EMS activation for football
      injury, 59.9% vs 27.5%; P < 0.01) and reported fewer pre-season planning meetings
      (eg, met with EMS to practice, 38.1% vs 55.8%; P < 0.01). During the Fall 2008
      football season, high school ATs perceived more episodes of inappropriate care
      (10.4% vs 3.9%; P < 0.01) and on-field disagreements (5.4 vs 2.2%; P < 0.01) than
      collegiate ATs. High school work setting was independently associated with
      episodes of AT-perceived inappropriate care (adjusted OR = 2.76; 95% CI, 1.65
      4.62) and on-field disagreements (adjusted OR = 2.33; 95% CI, 1.17-4.64).
      CONCLUSIONS: Athletic trainer-EMS interactions are common and sometimes involve
      AT-perceived episodes of inappropriate care and on-field disagreements between
      emergency care providers.

PMID- 21079440
TI  - Risk taking in avalanche terrain: a study of the human factor contribution.
AB  - OBJECTIVE: To discover possible associations between the human factors and
      avalanche incidents. DESIGN: Self-report, intercept, and Web-based, 1-year
      retrospective, cross-sectional study. SETTING: Mountain Equipment Co-op stores in
      Calgary and Vancouver, Canada. PARTICIPANTS: People shopping at the store and who
      had entered avalanche terrain in the past 12 months were invited to complete the
      survey (n = 447). INDEPENDENT VARIABLES: Sex, age, sport activity, days of
      exposure, years of experience, socioeconomic status, level of training, risk
      propensity, and motivation. MAIN OUTCOME MEASURES: Experiencing an avalanche
      incident. RESULTS: Women and those traveling with women were less likely to
      experience an avalanche incident [odds ratio (OR) = 0.45; 95% confidence interval
      (CI), 0.21-0.96]. Those with the most training were more likely to report
      experiencing an avalanche incident (OR = 6.86; 95% CI, 2.37-19.83), but this
      difference was attenuated (OR = 2.25) and not statistically significant (95% CI,
      0.57-8.81) after adjustment for exposure. Experience was not found to be a
      factor. Being motivated to seek intense experiences was found to be a factor (OR
      = 2.19; 95% CI, 1.03-4.66), whereas being motivated to create memorable
      experiences was protective (OR = 0.29; 95% CI, 0.10-0.86). CONCLUSIONS: The
      results of this study suggest that people exposing themselves to avalanche risk
      do so to satisfy inherited and learned motivational needs and that some
      motivations are associated with higher or lower risk taking than others. Training
      appears to be exploited so as to increase access to these benefits rather than
      reduce risk. Within this risk/reward paradigm, risk taking among men is moderated
      by the presence of a woman in the group.

PMID- 21079441
TI  - Electromyographic examination of selected muscle activation during isometric core
      exercises.
AB  - OBJECTIVE: The purpose of the current study was to quantitatively examine the
      muscle activations of 3 common isometric core exercises (abdominal bridge, single
      leg abdominal bridge, and superman) along with a newly introduced isometric
      exercise (flying squirrel) and determine if muscle activations differed among the
      exercises. DESIGN: The design was a comparison study. SETTING: An athletic
      training classroom laboratory was where all data collections occurred.
      PARTICIPANTS: Thirty healthy collegiate graduate students (age, 23.4 +/- 1.4
      year; height, 171.3 +/- 10.3 cm; mass, 73.3 +/- 16.2 kg), regardless of sex,
      consented to participate. INDEPENDENT VARIABLE: The independent variable was the
      muscle selected. MAIN OUTCOME MEASURES: The main outcome measures or dependent
      variables were the muscle activation reported as percent of maximum voluntary
      isometric contraction during each exercise. RESULTS: Results revealed that the
      multifidi produced the greatest muscle activity in all exercises, and the single
      leg abdominal bridge exercise produced greater muscle activation than the general
      abdominal bridge exercise (P < 0.025). CONCLUSIONS: The findings of this study
      demonstrate that any of these exercises may be a part of a core stability
      program. In addition, these findings may be incorporated into an isometric core
      exercise program to supplement a currently implemented isometric core exercise
      program.

PMID- 21079442
TI  - Measurement characteristics of a force-displacement curve for chronic patellar
      instability.
AB  - OBJECTIVE: The clinical diagnosis of patellar instability is subjective,
      depending on the patient's apprehension. We hypothesized that a subjective
      diagnosis could be supported by a numerical evaluation of the slope, or
      compliance, of the early phase of a force-displacement curve. DESIGN: Cross
      sectional control group comparison. SETTING: A university-based sports clinic.
      PARTICIPANTS: Healthy volunteers (n = 21; 16-40 years old) and patients (n = 21;
      15-34 years old) who had a clearly definable diagnosis of unilateral dislocation,
      followed by chronic anterior knee pain, and positive apprehension signs for more
      than 6 months, without patella alta or abnormal limb alignment. INTERVENTION:
      Lateral displacement and reactive forces were measured with a Patella Stability
      Tester. MAIN OUTCOME MEASURES: Sensitivity in detecting injured knees was
      defined, with the 95% confidence interval of healthy subjects determined as the
      normal range. RESULTS: Compliance at 5 mm in displacement showed the highest
      reproducibility (plot difference of 4.7%) and the highest sensitivity (95%).
      Among injured knees, compliance was significantly correlated with the activity
      related symptoms of the Kujala score (correlation coefficient, -0.61; P = 0.004).
      Compliance at 5 mm of displacement showed the highest sensitivity (95%) and
      significant correlation with the activity-related symptoms of the Kujala score
      among injured knees (coefficient of determination, 0.37; P = 0.004). CONCLUSIONS:
      It is a novel finding that early compliance at 5 mm of displacement showed a
      correlation with the subjective diagnosis and symptoms.

PMID- 21079443
TI  - Apolipoprotein E genotype and concussion in college athletes.
AB  - OBJECTIVE: To evaluate the association between apolipoprotein E (APOE)
      polymorphisms (E2, C/T Arg158Cys; E4, T/C Cys112Arg; and promoter, g-219t) and
      the history of concussion in college athletes. We hypothesized that carrying 1 or
      more APOE rare (or minor) allele assessed in this study would be associated with
      having a history of 1 or more concussions. DESIGN: Multicenter cross-sectional
      study. SETTING: University athletic facilities. PARTICIPANTS: One hundred ninety
      six male football (n = 163) and female soccer (n = 33) college athletes
      volunteered. INTERVENTIONS: Written concussion history questionnaire and saliva
      samples for genotyping. MAIN OUTCOME MEASURES: Self-reported history of a
      documented concussion and rare APOE genotype (E2, E4, promoter). RESULTS: There
      was a significant association (Wald chi2 = 3.82; P = 0.05; odds ratio = 9.8)
      between carrying all APOE rare alleles and the history of a previous concussion.
      There was also a significant association (Wald chi2 = 3.96, P = 0.04, odds ratio
      = 8.4) between carrying the APOE promoter minor allele and experiencing 2 or more
      concussions. CONCLUSIONS: Carriers of all 3 APOE rare (or minor) alleles assessed
      in this study were nearly 10 times more likely to report a previous concussion
      and may be at a greater risk of concussion versus noncarriers. Promoter minor
      allele carriers were 8.4 times more likely to report multiple concussions and may
      be at a greater risk of multiple concussions versus noncarriers. Research
      involving larger samples of individuals with multiple concussions and carriers of
      multiple APOE rare alleles is warranted.

PMID- 21079444
TI  - Skeletal age in youth soccer players: implication for age verification.
AB  - OBJECTIVE: To evaluate variation in skeletal age (SA) within single-year
      chronological age (CA) groups of soccer players aged 11 to 17 years in the
      context of using SA for age verification in age-group competitions. DESIGN: Cross
      sectional. SETTING: Regional and elite youth soccer programs. PARTICIPANTS: Five
      hundred ninety-two male players from Portugal and Spain. INDEPENDENT VARIABLES:
      Skeletal age assessed with the Fels method. MAIN OUTCOME MEASURES: Skeletal age
      and maturity status (late, average, early, or mature). RESULTS: Chronological age
      and SA overlapped in players aged 11 to 12 years, but SA was advanced relative to
      CA in players aged 14 to 16 years. The majority of players between 11 and 12
      years of age were on time in skeletal maturity and percentages of late and early
      maturers did not differ. The majority of players between 13 and 14 years of age
      were also on time, but early maturers were 4 times more frequent than late
      maturers. Percentages of late maturers were low among players aged 14 to 16
      years. Among 200 players aged 15 to 16 years, 80 (40%) were advanced in SA by > 1
      year and 27 (14%) were skeletally mature, whereas among 23 players aged 17 years,
      9 (39%) were skeletally mature. CONCLUSIONS: Among adolescent soccer player, boys
      advanced in SA for CA are overrepresented and those later in SA for CA are
      underrepresented with increasing CA. If Fels SA was used to verify CA in this
      sample of youth for under-17 competition, 36 skeletally mature players aged 15 to
      17 years (16%) would be disqualified. The results for this sample of male soccer
      players question the utility of SA or magnetic resonance imaging as a valid
      estimate of CA in youth sport competitions.

PMID- 21079445
TI  - Women and anabolic steroids: an analysis of a dozen users.
AB  - OBJECTIVE: To provide an in-depth analysis of 12 female self-reported anabolic
      androgenic steroid (AAS) users. DESIGN: Web-based survey. SETTING: A Web-based
      survey was posted on 38 discussion boards of various fitness, bodybuilding,
      weightlifting, and steroid Web sites between February and June 2009.
      INTERVENTIONS: Participants completed a survey regarding demographics and use of
      AAS and other performance-enhancing agents (PEAs). PARTICIPANTS: A cohort of 1519
      strength-trained subjects fully completed and submitted a valid survey. Five
      hundred eighteen subjects were self-reported AAS users consisting of 12 women and
      506 men. One thousand one subjects were non-AAS users consisting of 230 women and
      771 men. MAIN OUTCOME MEASURES: Demographic data and use of AAS and other PEAs.
      RESULTS: The female AAS users reported using an average of 8.8 PEAs in their
      routine. Compared with male AAS users and female non-AAS users, respectively,
      female AAS users were more likely to have met criteria for substance-dependence
      disorder (58.3% vs 23.4%; P = 0.01; 58.3% vs 9.1%; P < 0.001), have been
      diagnosed with a psychiatric illness (50.0% vs 17.4%; P = 0.01; 50.0% vs 22.2%; P
      = 0.04), and have reported a history of sexual abuse (41.7% vs 6.1%; P < 0.001;
      41.7% vs 15.3%; P = 0.03). CONCLUSIONS: Female AAS users practice polypharmacy.
      Female AAS users are more likely to have qualified for substance-dependence
      disorder, have been diagnosed with a psychiatric illness, and have a history of
      sexual abuse than both male AAS users and female non-AAS users.

PMID- 21079446
TI  - A study of serum sodium level among Hong Kong runners.
AB  - OBJECTIVE: Hyponatremia and the associated life-threatening complications have
      emerged as an important issue among marathon runners. This study was conducted to
      estimate the serum sodium level among local marathon runners and to identify the
      associated risk factors of dysnatremia. DESIGN: Prospective observational cohort
      study. SETTING: Hong Kong Marathon 2008. PARTICIPANTS: Subjects were approached
      at their convenience to participate in the study. Only full-marathon runners were
      recruited. They were to have had an unremarkable medical and drug history.
      INTERVENTIONS: Demographic data, training information, previous marathon
      experience, anticipated drinking strategy, details of fluid consumption
      throughout the race, weight change, finishing time, and physical complaint. MAIN
      OUTCOME MEASURES: Post-race serum sodium level. RESULTS: Of the 6488 entries to
      the race, 370 runners (5.7%) were recruited. Among them, 272 (73.5%) completed
      the race and attended for blood sampling and data collection. One runner (0.4%)
      had hyponatremia (133 mmol/L) and 35 runners (12.9%) had hypernatremia (>145
      mmol/L), whereas 236 runners (86.7%) had normal serum sodium (135-145 mmol/L)
      after the race. No symptomatic dysnatremia was found. A mean weight reduction of
      0.70 kg was found after the race. An average of 1.9 L of fluid was consumed
      during the race and 2.5 L if the fluid consumed immediately before and after the
      race was also included. Hypernatremia was seen in runners who were better trained
      before the race, those who performed better, and those who drank less water after
      the race. CONCLUSIONS: This is the largest prospective observational cohort study
      of dysnatremia conducted on athletes completing a standard marathon in Asia. No
      case of symptomatic dysnatremia was found.

PMID- 21079447
TI  - Should ultrasound-guided needle fenestration be considered as a treatment option
      for recalcitrant patellar tendinopathy? A retrospective study of 47 cases.
AB  - OBJECTIVE: To report the retrospective results of ultrasound-guided needle
      fenestration for the treatment of recalcitrant patellar tendinopathy. DESIGN:
      Retrospective follow-up study. SETTING: University outpatient sports medicine
      clinic. PATIENTS: Forty-seven patellar tendons in 32 patients (26 men and 6
      women; mean age, 26 years) with recalcitrant patellar tendinopathy. Diagnosis
      made via history, physical examination, and sonographic examination.
      INTERVENTION: Ultrasound-guided needle fenestration after failure of conservative
      management. MAIN OUTCOME MEASURES: Pre-treatment and 4-week clinical follow-up
      determination of functional activity score. Phone follow-up determination of best
      achievable level of activity and satisfaction score of the procedure. RESULTS:
      Average time to follow-up was 45 months. Seventy-two percent of patients reported
      excellent or good results when questioned regarding return to activity. Twenty
      eight percent of patients were unable to return to their desired activity level.
      Six patients subsequently underwent surgical treatment. One athlete underwent
      surgery to repair a patellar tendon rupture that occurred 6 weeks after the
      procedure. Eighty-one percent of patients reported excellent or good satisfaction
      scores. CONCLUSIONS: Ultrasound-guided needle fenestration warrants further
      investigation for the treatment of recalcitrant patellar tendinopathy.

PMID- 21079448
TI  - The influence of pediatric autonomic dysfunction on recovery after concussion.

PMID- 21079449
TI  - Nonoperative treatment of a complete distal rectus femoris muscle tear.

PMID- 21079450
TI  - A case report of myositis ossificans traumatica in the adductor magnus.

PMID- 21079451
TI  - Scuba diving and portal vein thrombosis: a case report.

PMID- 21079452
TI  - Is the risk of injury greater in Pee Wee hockey leagues that permit body
      checking?

PMID- 21079453
TI  - Improving strength and fitness in elderly women through long-term exercise.

PMID- 21079455
TI  - Impact exercise and postmenopausal bone loss: a review.

PMID- 21079454
TI  - Surgery or physiotherapy for small and medium-sized rotator cuff tears?

PMID- 21079456
TI  - Evidence for use of mood stabilizers and anticonvulsants in the treatment of
      nonaffective disorders in children and adolescents.
AB  - Mood stabilizers and anticonvulsants have been frequently used to control
      behaviors in children and adolescent with nonaffective disorders. The purpose of
      this study was to review the literature to evaluate the evidence of these agents
      as treatment options in this subset of patients. We reviewed all the literature
      between 1949 and 2009 on the use of anticonvulsants and mood stabilizers in
      controlling severe behavior dysregulation and aggression in child and adolescent
      who do not meet the criteria for any mood disorder. The review revealed a total
      of 19 studies. Of the different mood stabilizers/anticonvulsants, both lithium
      and divalproex showed some promise in treating children and adolescents with
      nonmood disorders. Larger studies are nevertheless needed to support the ongoing
      use of these current anticonvulsants and mood stabilizers in children and
      adolescents with nonmood disorders. Also, further investigation to the potential
      use in the long term would need to be established, bearing in mind the balance of
      side effects and treatment benefit.

PMID- 21079457
TI  - Severe depression, suicide attempts, and ideation during the use of interferon
      beta by patients with multiple sclerosis.
AB  - BACKGROUND: Interferon (IFN) beta is a safe and efficient drug for treating
      multiple sclerosis (MS). It is widely accepted that previously depressed patients
      may get worse when using IFN-beta. There are few reports on the association of
      IFN-beta and severe depression among patients without previous psychiatric
      history. METHODS: Discussion of a case of a patient with MS who developed severe
      depression and attempted suicide while using IFN-beta encouraged us to review the
      subject. A group of neurologists in Brazil retrospectively gathered together
      their similar cases for the present paper. RESULTS: The present paper reports on
      11 cases of severe depression with suicide attempts or ideation among patients
      with MS who were using IFN-beta. These patients had no previous history of any
      psychiatric disease. Nine patients developed the symptoms over a relatively short
      period (4 months, on average). Two patients developed severe depression after
      more than 1 year of treatment with IFN-beta. Phobic, aggressive, behavioral,
      psychotic, and manic symptoms also were observed in these patients, thus
      suggesting the existence of a complex mood-behavior disorder associated with this
      drug. Interferon beta withdrawal led to complete remission of symptoms. The
      Naranjo algorithm established a highly probable association between IFN-beta and
      this adverse reaction in these patients. CONCLUSIONS: Although uncommon, severe
      depression with suicide ideation or attempts may be observed during treatment of
      MS with IFN-beta. This association should not discourage the use of this drug,
      but physicians need to be aware of this possible adverse event from IFN-beta.

PMID- 21079458
TI  - Successful treatment of cerebellar ataxia and tremor in multiple sclerosis with
      topiramate: a case report.
AB  - We describe the clinical efficacy of topiramate for treatment of cerebellar
      dysfunction in a 33-year-old female patient with relapsing remitting multiple
      sclerosis. The patient presented severe ataxia and tremor precluding many
      activities of daily life. Topiramate was administered as a monotherapy and slowly
      tapered in to 150 mg daily without negative side effects. Treatment was well
      tolerated and led to a marked and lasting improvement of tremor as well as ataxia
      during an observation period of 2 years. Upon transient withdrawal of topiramate,
      ataxia and tremor worsened but were again improved after re-dosing of the drug.
      Multiple sclerosis immunotherapy was not changed in this period. In conclusion,
      topiramate may be a new therapeutic option to treat cerebellar tremor and ataxia
      in patients with multiple sclerosis.

PMID- 21079459
TI  - Effectiveness of quetiapine for poststroke pathological laughing: case report and
      review of the literature.
AB  - Pathological laughing (PL) is an uncommon distressing symptom that occurs in
      patients with various neurological disorders. Dysregulation of serotonergic
      system has been proposed as one of the possible mechanisms resulting in this
      condition, and selective serotonin reuptake inhibitors have been used for
      treatment of PL with variable effects. However, the pathogenetic mechanism of PL
      remains largely elusive, and other treatment choices needs to be explored. This
      case report illustrates the beneficial effect of quetiapine, an atypical
      antipsychotic agent with enhancing serotonergic neurotransmitter activity, in a
      patient with post-stroke PL. In addition, previously reported post-stroke PL
      cases searched from PubMed (1993-2010) were also reviewed. In this report, we
      demonstrate a 42-year-old man who developed PL 4 weeks after a hemorrhage stroke
      affecting the paramedian pons. He was treated with dextromethorphan initially but
      did not show obvious response. Then, the medication was shifted to quetiapine at
      a dosage of 25 mg/d. There was a significant and rapid recovery 2 days after
      quetiapine treatment. Our observations expand the current knowledge of treatment
      of PL caused by pontine lesions. Further large-scale controlled trials are
      warranted to evaluate the beneficial and differential effects of quetiapine on
      PL.

PMID- 21079460
TI  - Encephalitis lethargica with quick response to immunoglobulin.

PMID- 21079461
TI  - Accreditation--we passed!

PMID- 21079462
TI  - Challenges and successes of putting health care-associated infection public
      reporting laws into practice.

PMID- 21079463
TI  - Administration of local anesthetic agents to decrease pain associated with
      peripheral vascular access.
AB  - The purpose of this study was to compare a variety of local anesthetic agents
      before starting an intravenous (i.v.) device to determine which method is the
      most comfortable for patients. Using a randomized, double-blind, placebo
      controlled, pretest-posttest experimental design, the study compared 5 treatment
      groups (anesthetic spray, placebo spray, anesthetic intradermal injection,
      placebo intradermal injection, and a control group with no local anesthetic
      agent) in 84 emergency department patients. Pain was measured with a visual
      analog scale before and after the application of the local anesthetic agents and
      after i.v. insertion. Pain was significantly higher in the anesthetic intradermal
      injection group 1 minute after anesthetic application compared with the other
      treatment groups. Pain ratings 3 minutes after i.v. insertion were found to be
      similar for the 5 treatment groups. These study results do not support the use of
      intradermal anesthetic agents before i.v. catheter insertion.

PMID- 21079464
TI  - Emergence of infection control surveillance in alternative health care settings.
AB  - During the past decade, health care delivery has undergone enormous changes. The
      nationwide growth in managed care organizations and the changing methods of
      provider reimbursement are restructuring the entire health care system.
      Diversification and integration strategies have blurred historical separations
      between the activities of hospitals, nursing homes, physicians, and other
      providers. Services are being offered in and shifting to less costly settings,
      such as ambulatory clinics, work sites, and homes. Many factors have contributed
      to the increasing trend of health care delivery outside hospitals. This
      presentation will provide insight to the management and surveillance of infection
      prevention in these health care settings.

PMID- 21079465
TI  - A randomized controlled trial to compare the complications of 2 peripheral
      intravenous catheter-stabilization systems.
AB  - An open-label, prospective, randomized, noninferiority study was conducted at a
      large academic, Magnet-designated, Level I trauma center to compare the
      peripheral intravenous catheter securement-related complication rates of 2
      different stabilization systems. The control stabilization system included the
      StatLock device with a nonwinged catheter, and the investigational stabilization
      system included a closed catheter system with a specially designed Tegaderm
      dressing. Data from 302 subjects indicated that the investigational stabilization
      system was noninferior or similar to the control stabilization system with
      respect to the overall securement-related complications. The cost of the
      investigational stabilization system was approximately 75% of the cost for the
      control stabilization system.

PMID- 21079466
TI  - Evaluation of the psychometric properties of the phlebitis and infiltration
      scales for the assessment of complications of peripheral vascular access devices.
AB  - To prevent complications from peripheral vascular access device (PVAD) therapy,
      the Infusion Nurses Society (INS) developed 2 scales to measure the extent and
      severity of phlebitis and infiltration in PVADs. This study evaluated the
      psychometric properties of these scales to validate them with respect to their
      interrater reliability, concurrent validity, feasibility, and acceptability. A
      total of 182 patients at 2 sites were enrolled, and 416 observations of PVAD
      sites were made. Two nurses independently rated each PVAD site for the presence
      or absence of phlebitis and/or infiltration by using the INS scales. The
      interrater reliability was calculated, as was the agreement of the observed
      versus charted incidence of phlebitis and infiltration (concurrent validity) and
      the ease of use of the scales (feasibility, acceptability). Interrater
      reliability for both the Phlebitis and Infiltration scales and concurrent
      validity were found to be statistically significant (P < .05). The study nurses
      reported the scales to be easy to use, taking an average of 1.3 minutes to
      complete both. The importance of valid measures for use in research cannot be
      underestimated. The INS Phlebitis and Infiltration scales have been shown to be
      easy to use, valid, and reliable scales.

PMID- 21079467
TI  - Intestinal transplant: the long and short of it.
AB  - Intestinal failure (IF), typically due to short bowel syndrome in adults and
      congenital disorders in pediatric patients, is universally managed with
      parenteral nutrition (PN). When patients fail PN due to recurrent infection, loss
      of central venous access or PN-induced liver disease, intestinal transplant (ITx)
      is indicated. ITx consists of transplant of the small bowel, small bowel plus
      liver, or intestine plus multiple abdominal viscera. ITx allows for freedom from
      PN but is complicated by rejection and infection. Early referral of patients with
      IF to centers with experience in intestinal rehabilitation and transplantation is
      essential to improve patient outcome.

PMID- 21079474
TI  - Which core body temperature measurement method is most accurate?

PMID- 21079468
TI  - Implementing a better bundle to achieve and sustain a zero central line
      associated bloodstream infection rate.
AB  - The objective of every health care facility is achieving and maintaining a zero
      central line-associated bloodstream infection (CLABSI) rate. Interventions to
      enhance care were put into place, and changes in CLABSI rates were tracked. Data
      were collected from January 2003 through June 2009. The interventions included
      the following: a dedicated vascular access team; swabbable clear positive
      displacement needleless connector; chlorhexidine-impregnated disk; flushing with
      20 mL of normal saline; rigorous central line care education; increased use of
      peripherally inserted central catheters; and daily review of necessity. A
      significant drop to zero CLABSIs occurred after the introduction of several new
      central line care practices.

PMID- 21079477
TI  - Urinary incontinence.

PMID- 21079479
TI  - The best holiday gift.

PMID- 21079480
TI  - It all started on Kilimanjaro Our lives as travel nurses.

PMID- 21079481
TI  - Keeping your cool with difficult family members.

PMID- 21079482
TI  - Working with percutaneous endoscopic gastrostomy tubes in adults.

PMID- 21079483
TI  - Sounds soothing: music therapy for postoperative pain.

PMID- 21079484
TI  - The ABCs of safety and quality.

PMID- 21079486
TI  - Double jeopardy: pneumococcal pneumonia following seasonal influenza.

PMID- 21079487
TI  - Demystifying skin tears, part 1.

PMID- 21079489
TI  - Symptomatic bradycardia.

PMID- 21079492
TI  - What's New in Shock, December 2010?

PMID- 21079493
TI  - Does hypercapnic acidosis preserve mucosal oxygenation during hemorrhage?

PMID- 21079494
TI  - Re: Barz T, Melloh M, Staub LP, et al. Nerve root sedimentation sign. Evaluation
      of a new radiological sign in lumbar spinal stenosis. Spine 2010;35:892-7.

PMID- 21079495
TI  - Re: Ivo R, Sobottke R, Seifert H, et al. Tuberculous spondylitis and
      paravertebral abscess formation after kyphoplasty: a case report. Spine
      2010;35:E559-63.

PMID- 21079500
TI  - Anatomy and biomechanics of the posterior cruciate ligament, medial and lateral
      sides of the knee.
AB  - The evaluation and management of posterior cruciate ligament (PCL) injuries
      presents a clinical challenge to even the most experienced orthopedic surgeons.
      Increasing emphasis has also been placed on the diagnosis of associated
      ligamentous and cartilaginous injuries that may contribute to patterns of
      instability not solely attributed to the PCL deficiency. Although a uniformly
      accepted surgical technique to restore the anatomy and biomechanics of the
      multiligament injured knee does not exist, careful identification and management
      of additional ligamentous injuries are critical in achieving optimum results and
      avoid further insult or degradation of the knee joint owing to continued
      instability. Knowledge of the PCL anatomy and associated structures, combined
      with a clinical understanding of the biomechanics of the native tissues assist
      the orthopedic surgeon in treating these difficult injuries.

PMID- 21079498
TI  - Clinical acceptance and accuracy assessment of spinal implants guided with
      SpineAssist surgical robot: retrospective study.
AB  - STUDY DESIGN: Retrospective, multicenter study of robotically-guided spinal
      implant insertions. Clinical acceptance of the implants was assessed by
      intraoperative radiograph, and when available, postoperative computed tomography
      (CT) scans were used to determine placement accuracy. OBJECTIVE: To verify the
      clinical acceptance and accuracy of robotically-guided spinal implants and
      compare to those of unguided free-hand procedures. SUMMARY OF BACKGROUND DATA:
      SpineAssist surgical robot has been used to guide implants and guide-wires to
      predefined locations in the spine. SpineAssist which, to the best of the authors'
      knowledge, is currently the sole robot providing surgical assistance in
      positioning tools in the spine, guided over 840 cases in 14 hospitals, between
      June 2005 and June 2009. METHODS: Clinical acceptance of 3271 pedicle screws and
      guide-wires inserted in 635 reported cases was assessed by intraoperative
      fluoroscopy, where placement accuracy of 646 pedicle screws inserted in 139
      patients was measured using postoperative CT scans. RESULTS: Screw placements
      were found to be clinically acceptable in 98% of the cases when intraoperatively
      assessed by fluoroscopic images. Measurements derived from postoperative CT scans
      demonstrated that 98.3% of the screws fell within the safe zone, where 89.3% were
      completely within the pedicle and 9% breached the pedicle by up to 2 mm. The
      remaining 1.4% of the screws breached between 2 and 4 mm, while only 2 screws
      (0.3%) deviated by more than 4 mm from the pedicle wall. Neurologic deficits were
      observed in 4 cases yet, following revisions, no permanent nerve damage was
      encountered, in contrast to the 0.6% to 5% of neurologic damage reported in the
      literature. CONCLUSION: SpineAssist offers enhanced performance in spinal surgery
      when compared to free-hand surgeries, by increasing placement accuracy and
      reducing neurologic risks. In addition, 49% of the cases reported herein used a
      percutaneous approach, highlighting the contribution of SpineAssist in procedures
      without anatomic landmarks.

PMID- 21079501
TI  - Initial evaluation of posterior cruciate ligament injuries: history, physical
      examination, imaging studies, surgical and nonsurgical indications.
AB  - Compared with anterior cruciate ligament injuries, posterior cruciate ligament
      injuries are a rare event. The mechanisms are predictable and a thorough physical
      examination is mandatory to rule out or define combined injury patterns. Stress
      radiography and magnetic resonance imaging studies are very helpful adjuncts.
      Acute and chronic injuries require slightly different approaches. As our
      understanding of normal and pathologic knee joint kinematics develops,
      nonoperative rehabilitation goals and operative techniques continue to evolve.

PMID- 21079502
TI  - Single bundle posterior cruciate ligament reconstruction: surgical technique and
      results.
AB  - Posterior cruciate ligament (PCL) injuries are not that common but chronic PCL
      deficiency can lead to chronic disability and functional limitations. In these
      situations, the PCL reconstruction can be done. It is also commonly carried out
      during the treatment of a multiligament injured knee. Several different surgical
      techniques are described in the literature. This article outlines our surgical
      approach using the single bundle technique. We also carried out a review of the
      clinical and biomechanical studies concerning the single bundle PCL
      reconstruction.

PMID- 21079503
TI  - Double bundle posterior cruciate ligament reconstruction: surgical technique and
      results.
AB  - The keys to successful posterior cruciate ligament reconstruction are to identify
      and treat all pathology, use strong graft material, accurately place tunnels in
      anatomic insertion sites, minimize graft bending, use a mechanical graft
      tensioning device, use primary and back-up graft fixation, and use the
      appropriate postoperative rehabilitation program. Adherence to these technical
      principles results in successful single and double-bundle arthroscopic
      transtibial tunnel posterior cruciate ligament reconstruction based upon stress
      radiography, arthrometer, knee ligament rating scales, and patient satisfaction
      measurements.

PMID- 21079504
TI  - Tibial inlay posterior cruciate ligament reconstruction: surgical technique and
      results.
AB  - Posterior cruciate ligament (PCL) injuries occur much less frequently than other
      ligament injuries of the knee such as anterior cruciate ligament injuries. There
      is general agreement for nonoperative treatment for lower grade injuries such as
      type I PCL injuries. However, for more severe injuries which may require surgery,
      there is no consensus on an optimal reconstruction method. Multiple arthroscopic
      and open techniques exist to reconstruct the PCL. Limited clinical outcomes data
      reveals good short-term clinical results with different reconstruction options.
      Biomechanical data has helped further the understanding regarding the performance
      of different reconstructions. This article will present a surgical technique for
      single bundle tibial inlay reconstruction of the PCL along with the objective
      biomechanical data that supports this reconstruction.

PMID- 21079505
TI  - Posterolateral instability of the knee: evaluation, treatment, results.
AB  - Injuries to the fibular collateral ligament and posterolateral corner are
      uncommon, and are usually associated with other ligamentous injuries-in
      particular, the anterior cruciate ligament and/or posterior cruciate ligament,
      leading to significant functional impairment. The most common mechanism of injury
      for this area of the knee involves a combined hyperextension and varus force that
      is frequently of high energy. As these injuries occur typically in the setting of
      a multiligament-injured knee, the diagnosis and surgical reconstruction can be
      extremely challenging. This chapter will discuss the diagnosis of these injuries,
      including physical examination and imaging techniques, surgical timing, technical
      considerations, current controversies in management, and postoperative
      rehabilitation.

PMID- 21079506
TI  - Medial and posteromedial instability of the knee: evaluation, treatment, and
      results.
AB  - Medial-sided knee ligament injuries are complex and require a thorough
      understanding of the anatomy and the scope of injury to successfully treat.
      Patients with isolated medical collateral ligament (MCL) tears can normally be
      treated with bracing followed by physical therapy with outstanding results.
      Patients with isolated Grade III injuries to the MCL are controversial. A reason
      for the disparity in results reported may be due to the fact that many (if not
      most) Grade III MCL tears have associated injuries to the anterior cruciate
      ligament and/or posteromedial corner injury. Patients with combination injuries
      should be treated surgically with repair or reconstruction in most cases. Either
      allograft or autograft reconstructions of both the MCL and posteromedial corner
      can be successful. Successful elimination of anteromedial rotary instability is
      the key to successfully treating posteromedial corner injuries.

PMID- 21079507
TI  - Complications of posterior cruciate ligament surgery.
AB  - In addition to standard risks associated with all orthopedic surgical procedures,
      posterior cruciate ligament (PCL) reconstruction poses some relatively unique
      potential complications. These complications arise from a combination of several
      factors: the relative infrequency of PCL injuries, the lack of knowledge and
      experience in treating them, the proximity of neurovascular structures to the
      PCL, and the technically demanding nature of reconstructive procedures. This
      article discusses the anatomy, pathogenesis, and prevention of intraoperative and
      postoperative complications of PCL surgery including neurovascular injury,
      osteonecrosis, fracture, motion loss, and persistent laxity.

PMID- 21079508
TI  - Postoperative rehabilitation of the posterior cruciate ligament.
AB  - Diagnosis and management of posterior cruciate ligament injuries has evolved, and
      now the treatment often includes surgical intervention. The purpose of this paper
      is to define the current approach to postsurgical management after the posterior
      cruciate ligament reconstruction, review conservative management, and discuss
      surgical outcomes using a specified program.

PMID- 21079509
TI  - Outcomes of posterior cruciate ligament treatment: a review of the evidence.
AB  - OBJECTIVES: The purpose of this systematic review is to assess the current
      recommendations in an evidence-based manner with regard to posterior cruciate
      ligament (PCL) reconstruction. METHODS: We conducted a systematic review of
      multiple databases, evaluating studies on the outcomes of PCL treatment in
      isolation and in the multiligamentous injured knee. RESULTS: Twenty-one studies
      of isolated PCL reconstructions and 10 studies of combined PCL reconstruction
      were identified for inclusion. Eight studies reported graft failure as an
      outcome, with an overall rate of 11.6%. Three studies reported outcomes of single
      bundle PCL reconstruction using hamstring autograft; there were 12 graft failures
      in 96 reconstructions (12.5%). There were 2 graft failures in a total of 17
      combined PCL/anterior cruciate ligament/posterolateral corner reconstructions
      (11.8%). In the combined PCL studies, return to preinjury activity level ranged
      from 19 to 68%. In the isolated PCL studies, 50 to 82% of patients were able to
      return to preinjury activity level. There were no significant differences in
      functional outcomes (Lysholm and IKDC). From 37% to 70% of patients in the
      combined PCL studies had a normal posterior drawer test at final follow-up. One
      study showed a significant difference in the mean posterior drawer test side-to
      side difference between the 7-strand and 4-strand hamstring autograft groups (1.7
      vs. 3.7 mm, P<0.05). CONCLUSIONS: Currently, firm recommendations on what
      treatment or technique to choose cannot be given based upon the available
      literature. There is a need for higher-quality clinical studies to guide
      treatment decisions. Generally good results are reported after PCL
      reconstruction, but the long-term studies available suggest that normal stability
      in the majority of patients is not restored.

PMID- 21079512
TI  - A randomized, open-label pilot study comparing desirudin and argatroban in
      patients with suspected heparin-induced thrombocytopenia with or without
      thrombosis: PREVENT-HIT Study.
AB  - Because of an extreme risk for thromboemboli, patients with suspected heparin
      induced thrombocytopenia (HIT) require immediate initiation of an alternative
      anticoagulant. The only therapies approved by the Food and Drug Administration
      require intravenous infusion of expensive direct thrombin inhibitors. This
      prospective, randomized, open-label, exploratory study compared the clinical and
      economic utility of subcutaneous desirudin vs argatroban, the most frequently
      used agent for suspected or immunologically confirmed HIT, with or without
      thrombosis. Sixteen patients were randomized to treatment with fixed-dose
      desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time
      adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to
      direct thrombin inhibitor therapy, whereas Arm B included 8 patients on
      argatroban for at least 24 hours before randomization. The primary efficacy
      measure was the composite of new or worsening thrombosis (objectively
      documented), amputation, or death. Other end points included major and minor
      bleeding while on drug therapy, time to platelet count recovery, and
      pharmacoeconomics. No amputations or deaths occurred. One patient randomized to
      argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2
      patients on argatroban and in none during desirudin treatment. There was 1 minor
      bleed in each treatment group. The average medication cost per course of
      treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants
      further study as a potentially cost-effective alternative to argatroban in
      patients with suspected HIT.

PMID- 21079513
TI  - Lower liver stiffness in patients with sustained virological response 4 years
      after treatment for chronic hepatitis C.
AB  - OBJECTIVE: Transient elastography (TE) is a noninvasive and well validated method
      for measurement of liver stiffness. The aim of this study was to use TE to
      evaluate whether patients with sustained virological response (SVR) have lower
      liver stiffness than patients with non-SVR after treatment for chronic hepatitis
      C (CHC). METHODS: Patients with CHC, who had undergone liver biopsy before
      treatment with pegylated interferon and ribavirin, were included from four
      clinical centres in Denmark. All patients were examined with TE and had a blood
      test taken for hepatitis C virus-virus detection and analysis of alanine
      aminotransferase, platelet counts and hyaluronic acid. RESULTS: For 110 (92%) of
      the 120 patients included, it was possible to obtain a successful measurement of
      liver stiffness. Of these, 71 (64.5%) had achieved SVR. Median follow-up time was
      47 months. Patients with pretreatment minimal fibrosis (F0/F1) in their liver
      biopsy had median liver stiffness of 5.3 kPa for SVR versus 6.1 kPa for non-SVR
      (P=0.56). Patients with pretreatment moderate fibrosis (F2/F3) had median liver
      stiffness of 5.4 kPa for SVR versus 9.4 kPa for non-SVR (P<0.001). Median liver
      stiffness for patients with pretreatment cirrhosis (F4) was 6.8 kPa for SVR
      versus 24 kPa for non-SVR (P<0.001). CONCLUSIONS: Examination with TE 4 years
      after treatment shows that patients with CHC, who have achieved SVR, have
      significantly lower liver stiffness than patients with non-SVR. This indicates
      that histological liver outcome improves during the first year after the
      treatment for CHC.

PMID- 21079515
TI  - Chronic perineal pain: current pathophysiological aspects, diagnostic approaches
      and treatment.
AB  - Chronic perineal pain is the anorectal and perineal pain without underlying
      organic disease, anorectal or endopelvic, which has been excluded by careful
      physical examination, radiological and endoscopic investigations. A variety of
      neuromuscular disorders of the pelvic floor lead to the different pathological
      conditions such as anorectal incontinence, urinary incontinence and constipation
      of obstructed defecation, sexual dysfunction and pain syndromes. The most common
      functional disorders of the pelvic floor muscles, accompanied by perineal pain
      are levator ani syndrome, proctalgia fugax, myofascial syndrome and coccygodynia.
      In the diagnosis of these syndromes, contributing to a thorough history, physical
      examination, selected specialized investigations and the exclusion of organic
      disease with proctalgia is carried out. Accurate diagnosis of the syndromes helps
      in choosing an appropriate treatment and in avoiding unnecessary and ineffective
      surgical procedures, which often are performed in an attempt to alleviate the
      patient's symptoms.

PMID- 21079514
TI  - Family functioning and health-related quality of life in adolescents with
      pediatric inflammatory bowel disease.
AB  - OBJECTIVES: To examine the relationship between family functioning and health
      related quality of life (HRQOL) in a sample of adolescents with inflammatory
      bowel disease (IBD), and to specify the domains of family functioning with which
      these families experience difficulties. METHODS: Sixty-two adolescents, aged 13
      17 years, with a confirmed diagnosis of IBD completed assessments of HRQOL. Each
      adolescent's primary caregiver completed a measure of family functioning.
      Pediatric gastroenterologists provided data for disease severity assessments.
      RESULTS: A series of multivariate analyses of variance showed that adolescents
      from families with clinically elevated difficulties in problem solving,
      communication, and general family functioning endorsed lower HRQOL (i.e., social
      functioning, general well-being) after statistically controlling the effects of
      disease severity and diagnosis. As many as 25% of families reported clinically
      elevated difficulties across domains of family functioning. CONCLUSIONS: Findings
      suggest that family functioning may be an important predictor of HRQOL among the
      adolescents with IBD, and that many families experience difficulties in their
      daily interactions. Close monitoring of family functioning may be a salient
      feature for prevention and intervention efforts and beneficial in promoting
      optimal psychosocial outcomes among the adolescents with IBD.

PMID- 21079516
TI  - CD8 T-cell proliferative capacity is compromised in primary HIV-1 infection.
AB  - Understanding the correlates of immunity that control HIV-1 infection is
      imperative to our understanding of HIV-1 disease and vaccine development. HIV-1
      specific cytotoxic T lymphocytes are fundamental to the control of viremia;
      however, which T-cell repertoire components enact this control remains unclear.
      We hypothesize that polyfunctional HIV-1-specific CD8 T cells capable of viral
      control are present in most patients early in infection and these cells are
      distinguished by their ability to secrete interleukin (IL)-2 and proliferate. We
      examined HIV-1-specific CD8 T-cell proliferation and cytokine secretion in
      primary HIV-1 infection (PHI) using known HIV-1 cytotoxic T-cell epitopes to
      exclude CD4 bystander effect. We found that only a subset of patients with PHI
      demonstrated "CD4-independent" CD8 proliferation ex vivo. The remainder of the
      patients lacked HIV-1-specific CD8 T cells with proliferative capacity, even
      after the addition of exogenous IL-2. Among the proliferators, IL-2 production
      from the total HIV-specific CD8 T-cell population correlated with proliferation.
      Surprisingly, though, we did not routinely detect both IL-2 secretion and
      proliferative capacity from the same antigen-specific CD8 T cells. Thus, there
      are distinct and heterogeneous populations of CD8 T cells, phenotypically
      characterized by either proliferation or IL-2 secretion and few with dual
      capacity. Generation of these responses may be an important measure of HIV-1
      control but are not universal after PHI. Furthermore, the heterogeneity of this
      population suggests that a simple measure of an effective vaccine response
      remains elusive.

PMID- 21079517
TI  - Interatrial septal aneurysm and patent foramen ovale: diagnosis and dynamic
      evaluation with electrocardiogram-gated multidetector-row computed tomography
      imaging.
AB  - We describe an elderly woman with paroxysmal atrial fibrillation who was
      evaluated by electrocardiogram-gated multidetector-row computed tomography (MDCT)
      prior to left atrial radiofrequency ablation therapy to rule out coronary artery
      disease and to obtain a 3-dimensional anatomical map of the left atrium and
      pulmonary veins. MDCT documented the dynamic bidirectional motion of an
      interatrial septal aneurysm associated with a patent foramen ovale. MDCT findings
      correlated well with transesophageal and intracardiac echocardiograms.

PMID- 21079518
TI  - A case of malignant pleural mesothelioma with osseous and cartilaginous
      differentiation.
AB  - A 69-year-old man with a history of exposure to asbestos was admitted because of
      a chest radiographic abnormality. Subsequent findings from computed tomography
      and a thoracoscopic biopsy suggested malignant mesothelioma. Punctate
      calcification was observed in the pleural tumor on computed tomography scanning.
      The patient underwent pleuropneumonectomy, and the tumor was pathologically
      diagnosed as malignant mesothelioma, sarcomatoid type with osseous and
      cartilaginous differentiation. Malignant mesothelioma with osseous and
      cartilaginous differentiation is a rare condition. Punctate calcification in the
      pleural mass as a lesion distinct from the pleural plaque may indicate osseous or
      osteosarcomatous differentiation in malignant mesothelioma.

PMID- 21079519
TI  - The use of pleural fluid sCD44v6/std ratio for distinguishing mesothelioma from
      other pleural malignancies.
AB  - OBJECTIVE: Differentiating metastatic adenocarcinoma from malignant pleural
      mesothelioma is often a challenging task. Spliced forms of CD44, such as exon v6
      (CD44v6), have been implicated in tumor metastasis. We examined the diagnostic
      performance of soluble (s) CD44v6 and CD44 standard (sCD44std) as biomarkers for
      nonmesothelioma pleural malignancies in a retrospective series. METHODS: The
      pleural fluid from 161 patients with pleural effusion (33 mesotheliomas, 104
      nonmesothelioma malignancies, and 24 benign conditions) was analyzed for sCD44v6
      and sCD44std levels using an enzyme-linked immunosorbent assay kit. The ability
      of sCD44v6 and sCD44std levels and the sCD44v6/std ratio for distinguishing
      mesothelioma from nonmesothelioma malignancy were examined. RESULTS: Median
      pleural fluid concentrations of sCD44v6 but not sCD44std were significantly
      higher in patients with nonmesothelioma malignancy (101.5 ng/mL) than in those
      with mesothelioma (38 ng/mL, p < 0.0001). Fluids from metastatic squamous cell
      carcinomas exhibited particularly high sCD44v6 levels (388 ng/mL). A cutoff value
      of 100 ng/mL had the highest accuracy for distinguishing mesothelioma from
      nonmesothelioma malignancy (sensitivity 53% and specificity 88%) or metastatic
      adenocarcinoma (sensitivity 60% and specificity 88%). An sCD44v6/std ratio of
      more than 0.34 discriminated between adenocarcinoma and mesothelioma with a
      sensitivity of 60%, a specificity of 93%, a likelihood ratio positive of 9.97,
      and an area under the curve of 0.87 (95% confidence interval: 0.80-0.94).
      CONCLUSIONS: The pleural fluid sCD44v6/std ratio may be a new diagnostic marker
      in the differential diagnosis between primary mesothelioma and other pleural
      malignancies. Values greater than 0.34 predict nonmesothelioma malignancy and may
      be a help in determining whether an invasive thoracoscopy is necessary.

PMID- 21079520
TI  - Genome-wide association study on overall survival of advanced non-small cell lung
      cancer patients treated with carboplatin and paclitaxel.
AB  - PURPOSE: Our goal was to identify candidate polymorphisms that could influence
      overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients
      treated with carboplatin (CBDCA) and paclitaxel (PTX). METHODS: Chemotherapy
      naive stage IIIB or IV NSCLC patients treated with CBDCA (area under the curve =
      6 mg/mL/min) and PTX (200 mg/m, 3-hour period) were eligible for this study. The
      DNA samples were extracted from peripheral blood mononuclear cells before
      treatment, and genotypes at approximately 110,000 gene-centric single-nucleotide
      polymorphisms (SNPs) were obtained by Illumina's Sentrix Human-1 Genotyping
      BeadChip. Statistical analyses were performed by the log-rank test and Cox
      proportional hazards model. RESULTS: From July 2002 to May 2004, 105 patients
      received a total of 308 cycles of treatment. The median survival time (MST) of
      105 patients was 17.1 months. In the genome-wide association study, three SNPs
      were associated significantly with shortened OS after multiple comparison
      adjustment: rs1656402 in the EIF4E2 gene (MST was 18.0 and 7.7 months for AG [n =
      50] + AA [n = 40] and GG [n = 15], respectively; p = 8.4 * 10), rs1209950 in the
      ETS2 gene (MST = 17.7 and 7.4 months for CC [n = 94] and CT [n = 11] + TT [n =
      0]; p = 2.8 * 10), and rs9981861 in the DSCAM gene (MST = 17.1 and 3.8 months for
      AA [n = 75] + AG [n = 26] and GG [n = 4]; p = 3.5 * 10). CONCLUSION: Three SNPs
      were identified as new prognostic biomarker candidates for advanced NSCLC treated
      with CBDCA and PTX. The agnostic genome-wide association study may unveil
      unexplored molecular pathways associated with the drug response, but our findings
      should be replicated by other investigators.

PMID- 21079521
TI  - Sex differences in outcome with bevacizumab therapy: analysis of patients with
      advanced-stage non-small cell lung cancer treated with or without bevacizumab in
      combination with paclitaxel and carboplatin in the Eastern Cooperative Oncology
      Group Trial 4599.
AB  - INTRODUCTION: E4599 compared carboplatin and paclitaxel with (PCB) or without
      (PC) bevacizumab in patients with advanced-stage non-small cell lung cancer.
      Bevacizumab improved overall survival. However, an unplanned subset analysis did
      not show a survival benefit for females treated with bevacizumab. METHODS: Known
      prognostic factors and toxicities were compared by sex. Proportional hazards
      models of survival with multiple factor combinations were used to adjust for
      treatment effect. RESULTS: The analysis includes 850 patients. The median
      survival was 8.7 months (PC) versus 11.7 months (PCB) for males (p = 0.001) and
      13.1 months (PC) versus 13.3 months (PCB) for females (p = 0.87). Progression
      free survival and response rate on the PCB arm were 6.3 months and 29% for males
      and 6.2 months and 41% for females (p > 0.05). Progression-free survival and
      response rate on the PC arm were 4.3 months and 16% for males and 5.3 months and
      14% for females (p > 0.05). No significant demographic differences were seen
      between the two arms for males, whereas fewer females on the PCB arm had liver
      metastasis (PCB 11.7% versus PC 23.2%, p = 0.003). Adverse events with a sex
      difference on the PCB arm included severe hypertension (males: 4.2%, females:
      9.9%, p = 0.02), constipation (males: 1.4%, females: 4.7%, p = 0.05), and
      abdominal pain (males: 0.9%, females: 5.2%, p = 0.01). In the proportional
      hazards model adjusting for the other factors, the test for a sex by treatment
      interaction was not significant (p = 0.09). CONCLUSIONS: Multiple factors may
      contribute to the apparent sex-specific differences in efficacy of bevacizumab
      noted in this study.

PMID- 21079522
TI  - Positron emission tomography/computed tomography and lymphovascular invasion
      predict recurrence in stage I lung cancers.
AB  - BACKGROUND: Although pathologic stage I lung cancers generally have a favorable
      prognosis, approximately 20% of patients experience recurrence after surgery.
      Therefore, a method of selecting patients who need adjuvant therapy is necessary.
      The goal of this study was to evaluate the significance of positron emission
      tomography (PET)/computed tomography (CT) results after lung cancer surgery and
      to identify the predictive factors for recurrence in cases of pathologic stage I
      lung cancer. METHODS: From January 2004 to December 2008, 356 patients with lung
      cancer underwent surgery at our institution. Of these, 282 patients received F-18
      fluorodeoxyglucose PET/CT, and the maximum standardized uptake value (max SUV)
      was measured. There were 201 patients with pathologic stages IA and IB evaluated.
      The associations between disease-free survival (DFS) and the following
      clinicopathological factors were analyzed: age, gender, smoking history,
      carcinoembryonic antigen level, tumor size, max SUV values, histology, and
      lymphovascular and pleural invasion. RESULTS: The 4-year DFS rate was 86.3%.
      Multivariate analysis revealed lymphovascular invasion (LVI; p < 0.01) and max
      SUV >=4.7 (p < 0.01) to be independent predictive factors. Patients with a max
      SUV more than 4.7 had a significantly high risk of recurrence. DFS of patients
      with high max SUVs and LVI (n = 18) was significantly reduced compared with other
      patients (n = 183, p < 0.01). CONCLUSIONS: The PET-CT results significantly
      correlated with recurrence in pathologic stage I lung cancers. Patients with high
      max SUVs and LVI were more likely to have recurrence and should be candidates for
      adjuvant chemotherapy.

PMID- 21079523
TI  - Intratumoral lymphatic vessel involvement is an invasive indicator of completely
      resected pathologic stage I non-small cell lung cancer.
AB  - INTRODUCTION: Therapeutic strategies remain controversial for the completely
      resected stage I non-small cell lung cancer patients with worse long-term
      survival. Comprehensive patient selection for adjuvant chemotherapy should be
      based on proven risk factors. METHODS: The records of 610 patients with
      pathologic stage I complete pulmonary resection were retrospectively reviewed.
      Survival was analyzed by the Kaplan-Meier method, log-rank test, and Cox
      proportional hazards analysis. RESULTS: Overall 5-year survival rate was 75.1%.
      Univariate analysis for all patients revealed eight significant prognostic
      factors: age (p < 0.0001); gender (p = 0.0001); histopathology (p < 0.0001);
      differentiation (p < 0.0001); tumor size (T factor) (p < 0.0001); pleural
      involvement (p = 0.0007); blood vessel involvement (p < 0.0001); and lymphatic
      vessel involvement (p < 0.0001). Multivariate analysis revealed age, tumor size,
      and lymphatic vessel involvement as significant factors. Hazard ratios for death
      were 0.563 for age younger than 70 years (p = 0.0004), 0.629 for T1 tumor (p =
      0.0126), and 0.514 for ly(-) (p = 0.0002). Five-year survival rates in patients
      with T1 without lymphatic vessel involvement, T1 with lymphatic vessel
      involvement, T2 without lymphatic vessel involvement, and T2 with lymphatic
      vessel involvement were 88.7, 69.8, 73.5, and 56.1%, respectively. Overlapping
      prognoses were seen between T1 with lymphatic vessel involvement classed as stage
      IA and T2 without lymphatic vessel involvement classed as stage IB disease.
      CONCLUSIONS: Our analyses indicate lymphatic vessel involvement as an independent
      indicator of cancer invasiveness, surpassing the size-dependent tumor, node,
      metastasis staging system in pathologic stage I non-small cell lung cancer.
      Patients who would show survival benefits from adjuvant chemotherapy might be
      found by stratifying prognostic factors.

PMID- 21079524
TI  - Cost of breast cancer treatment in Medicaid: implications for state programs
      providing coverage for low-income women.
AB  - BACKGROUND: To date, no study has reported on the cost of treating breast cancer
      among Medicaid beneficiaries younger than 65 years of age. This information is
      essential for assessing the funding required for treatment programs established
      by the Breast and Cervical Cancer Prevention and Treatment Act of 2000.
      OBJECTIVE: This study assesses the incremental cost of breast cancer treatment
      among Medicaid beneficiaries aged below 65 years. RESEARCH DESIGN: Administrative
      data from the North Carolina Medicaid program linked with cancer registry data
      were analyzed to derive monthly Medicaid costs for cancer patients and the
      incremental costs of breast cancer treatment at 6, 12, and 24 months from
      diagnosis. We compared 848 beneficiaries diagnosed with cancer during the years
      2002 to 2004 with 1696 comparison cases matched on age. RESULTS: With the
      exception of in situ cancers, the cost of cancer care continued to increase
      beyond the initial 6-month period. The incremental costs at 6 months after
      diagnosis are $14,341, $24,002, and $34,469 for those with local, regional, and
      distant breast cancers, respectively; and these costs increased to $22,343,
      $41,005, and $117,033 at 24 months. CONCLUSIONS: The extended period of health
      care utilization, beyond the immediate 6-month period after diagnosis, indicates
      that Medicaid coverage may be required for many months after diagnosis to
      complete treatment. Continuous Medicaid coverage should be provided for an
      adequate time period to ensure that complete and comprehensive treatment is
      provided.

PMID- 21079525
TI  - Evaluation of patient centered medical home practice transformation initiatives.
AB  - BACKGROUND: The patient-centered medical home (PCMH) has become a widely cited
      solution to the deficiencies in primary care delivery in the United States. To
      achieve the magnitude of change being called for in primary care, quality
      improvement interventions must focus on whole-system redesign, and not just
      isolated parts of medical practices. METHODS: Investigators participating in 9
      different evaluations of Patient Centered Medical Home implementation shared
      experiences, methodological strategies, and evaluation challenges for evaluating
      primary care practice redesign. RESULTS: A year-long iterative process of sharing
      and reflecting on experiences produced consensus on 7 recommendations for future
      PCMH evaluations: (1) look critically at models being implemented and identify
      aspects requiring modification; (2) include embedded qualitative and quantitative
      data collection to detail the implementation process; (3) capture details
      concerning how different PCMH components interact with one another over time; (4)
      understand and describe how and why physician and staff roles do, or do not
      evolve; (5) identify the effectiveness of individual PCMH components and how they
      are used; (6) capture how primary care practices interface with other entities
      such as specialists, hospitals, and referral services; and (7) measure resources
      required for initiating and sustaining innovations. CONCLUSIONS: Broad-based
      longitudinal, mixed-methods designs that provide for shared learning among
      practice participants, program implementers, and evaluators are necessary to
      evaluate the novelty and promise of the PCMH model. All PCMH evaluations should
      as comprehensive as possible, and at a minimum should include a combination of
      brief observations and targeted qualitative interviews along with quantitative
      measures.

PMID- 21079527
TI  - Improving surveillance for pediatric Clostridium difficile infection: derivation
      and validation of an accurate case-finding tool.
AB  - BACKGROUND: The incidence of Clostridium difficile infection (CDI) is increasing.
      Multicenter studies of CDI have been limited by the lack of valid case-finding
      tools. To facilitate pediatric studies of CDI, we constructed a case-finding tool
      using administrative data. METHODS: A cross-sectional study was performed using
      the Pediatric Health Information System database and microbiologic data from 4
      member hospitals. Using patients with laboratory-confirmed CDI as the standard,
      we determined the sensitivity, specificity, positive (PPV), and negative (NPV)
      predictive value of an ICD-9-CM code for identifying children with laboratory
      confirmed CDI. RESULTS: We identified 109 patients with laboratory-confirmed CDI
      and 119 patients with CDI ICD-9-CM code. The sensitivity, specificity, PPV, and
      NPV were 80.73%, 99.89%, 73.95%, and 99.92%, respectively, for this comparison.
      The addition of a billing charge for both C. difficile laboratory test and
      treatment medication to the ICD-9-CM code increased the specificity and PPV, but
      resulted in a slight decrease in the sensitivity and NPV. The use of
      administrative data for identifying pediatric cases of CDI was also compared with
      that of chart review, and was found to be a stronger surrogate for identifying
      cases of CDI when compared with microbiology data alone. CONCLUSIONS: These
      results demonstrate that the use of administrative data for CDI is a reliable and
      accurate method for identifying pediatric patients with CDI. The use of
      administrative data could facilitate the completion of larger studies due to its
      greater accessibility and reduced costs.

PMID- 21079528
TI  - Vaccine Effectiveness Against Laboratory-confirmed Influenza in Healthy Young
      Children: A Case-Control Study.
AB  - BACKGROUND: the Western Australian Influenza Vaccine Effectiveness study
      commenced in 2008 to evaluate a new program to provide free influenza vaccine to
      all children aged 6 to 59 months. We aimed to assess the protective effect of
      inactivated influenza vaccination in these children. METHODS: We conducted a
      prospective case-control study in general practices and a hospital emergency
      department, testing all eligible patients for influenza and a range of other
      common respiratory viruses. Influenza vaccine effectiveness (VE) against
      laboratory-confirmed influenza was estimated with cases defined as children with
      an influenza-like illness who tested positive and controls as those with an
      influenza-like illness who tested negative for influenza virus. We calculated VE
      using the adjusted odds ratio from multivariate logistic regression. As a
      surrogate marker for adequate specimen collection, we explored the difference in
      VE point estimates defining controls as children in whom another respiratory
      virus was detected. RESULTS: a total of 75 children were enrolled from general
      practices and 214 through the emergency department, with 12 (27%) and 36 (17%),
      respectively, having laboratory-confirmed influenza. Using all the influenza
      negative controls, the adjusted VE was 58% (95% confidence interval, 9-81). When
      controls were limited to those with another virus present, the adjusted VE was
      68% (95% confidence interval, 26-86). CONCLUSIONS: VE estimates were higher when
      controls included only those children with another respiratory virus detected.
      Testing for other common respiratory viruses enables the control group to be
      restricted to those for whom an adequate sample is likely.

PMID- 21079526
TI  - Is patient-perceived severity of a geriatric condition related to better quality
      of care?
AB  - BACKGROUND: Care for falls and urinary incontinence (UI) among older patients is
      inadequate. One possible explanation is that physicians provide less recommended
      care to patients who are not as concerned about their falls and UI. OBJECTIVE: To
      test whether patient-reported severity for 2 geriatric conditions, falls, and UI,
      is associated with quality of care. RESEARCH DESIGN: Prospective cohort study of
      elders with falls and/or fear of falling (n = 384) and UI (n = 163). SUBJECTS:
      Participants in the Assessing Care of Vulnerable Elders-2 Study (2002-2003),
      which evaluated an intervention to improve the care for falls and UI among older
      (age, >= 75) ambulatory care patients with falls/fear of falling or UI. MEASURES:
      Falls Efficacy Scale (FES) and the Incontinence Quality of Life surveys measured
      at baseline, quality of care measured by a 13-month medical record abstraction.
      RESULTS: There was a small difference in falls quality scores across the range of
      FES, with greater patient-perceived falls severity associated with better odds of
      passing falls quality indicators (OR: 1.11 [95% CI: 1.02-1.21] per 10-point
      increment in FES). Greater patient-perceived UI severity (Incontinence Quality of
      Life score) was not associated with better quality of UI care. CONCLUSIONS:
      Although older persons with greater patient-perceived falls severity receive
      modestly better quality of care, those with more distressing incontinence do not.
      For both conditions, however, even the most symptomatic patients received less
      than half of recommended care. Low patient-perceived severity of condition is not
      the basis of poor care for falls and UI.

PMID- 21079529
TI  - Retrospective analysis and patient satisfaction assessment of insulin pump
      therapy in patients with type 2 diabetes.
AB  - OBJECTIVES: To evaluate and assess glycemic control, total daily insulin
      requirements, weight, and patient satisfaction after changing from multiple daily
      injections (MDI) to continuous subcutaneous insulin infusion (CSII) therapy in
      patients with type 2 diabetes. METHODS: This was a retrospective cross-sectional
      cohort analysis of an electronic medical records database from a private
      physician's clinic. Patients over 18 years of age who had type 2 diabetes and who
      utilized CSII for at least six months were analyzed. Variables of interest
      included glycosylated hemoglobin, total daily insulin requirements, and weight at
      the time of conversion from MDI to CSII. Patients were also asked to complete a
      satisfaction survey comparing MDI to CSII. RESULTS: Thirty patients who met the
      inclusion criteria were identified. Hemoglobin A1c (HbA1c) decreased from 9.25%
      +/- 2.20 to 7.94% +/- 1.65 (P < 0.001) at six months, total daily insulin dose
      decreased from 1.33 +/- 0.66 u/kg/day to 1.08 +/- 0.70 u/kg/day (P < 0.001) at
      six months, and weight increased from 106.66 +/- 19.17 kg to 109.75 +/- 18.01 kg
      (P < 0.001). After twelve months, HbA1c did not significantly change and weight
      returned to baseline; however, total daily insulin dose significantly decreased.
      95% of patients preferred CSII therapy to previous injection regimen for various
      reasons. CONCLUSION: Insulin pump therapy provided better glycemic control and
      reduced the total amount of insulin utilized. Patients who utilized CSII thought
      that the treatment was more convenient, less burdensome, and provided better
      control of fluctuations in blood glucose. CSII was preferred by patients over
      multiple daily injections.

PMID- 21079530
TI  - Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of
      interstitial lung disease and pulmonary hypertension.
AB  - Carbon monoxide (CO) has been widely recognized as an exogenous poison, although
      endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms,
      more specifically HO-1, in the setting of oxidative stress such as acute
      respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been
      studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO)
      therapy is used to selectively vasodilate the pulmonary vasculature and improve
      ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on
      binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the
      pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic
      dissemination. Several experimental design studies involving lab rats have
      demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of
      nitric oxide HO-1 induction.

PMID- 21079531
TI  - Overactive bladder: an urgent problem.

PMID- 21079532
TI  - Clinical significance of vitamin D deficiency in primary hyperparathyroidism, and
      safety of vitamin D therapy.
AB  - Vitamin D deficiency occurs more frequently in patients with primary
      hyperparathyroidism (PHPT) compared with the general population, and is usually
      associated with an aggravated form of the disease. Current guidelines recommend
      measurement of serum levels of 25-hydroxy vitamin D (25-OHD) in all patients with
      PHPT, and their repletion if the levels are less than 50 mmol/L (20 ng/mL).
      Limited data suggest that vitamin D treatment is generally safe in subjects with
      mild PHPT and coexisting vitamin D deficiency. Adverse effects include
      hypercalcuria and, less commonly, exacerbation of hypercalcemia. Well-designed
      trials are needed to evaluate the safety of vitamin D replacement therapy in a
      wide spectrum of patients with concomitant PHPT and vitamin D deficiency. These
      trials should address the impact of such therapy on the complications and course
      of PHPT.

PMID- 21079533
TI  - Adenoid cystic carcinoma of trachea treated with tumor curettage and adjuvant
      intensity modulated radiation therapy.
AB  - Primary tracheal tumors are rare, accounting for only 0.2% of all thoracic
      cancers. Adenoid cystic carcinoma (ACC) is the second most common tracheal
      malignancy. Most ACC patients present with dyspnea, and the symptoms often mimic
      those of asthma or chronic bronchitis. We report the case of a 79-year-old female
      patient who presented with dyspnea and wheezing, but showed poor response to
      bronchodilator treatment. Bronchoscopy revealed a lobulated tumor over the lower
      third of the trachea, and biopsy revealed adenoid cystic carcinoma. Tumor
      curettage followed by intensity modulated radiation therapy was performed, and
      the patient eventually recovered. This case demonstrates that such less invasive
      management also leads to a favorable outcome.

PMID- 21079534
TI  - Erythema multiforme secondary to H1N1 vaccine.

PMID- 21079535
TI  - Etiology and treatment of overactive bladder in women.
AB  - Overactive bladder (OAB) is a condition that affects millions of women in the
      United States (US). Although the etiology is largely unknown, risk factors
      include Caucasian race, insulin-dependent diabetes mellitus, and history of
      depression. Patients present with urgency with or without urinary incontinence
      and often have urinary frequency and nocturia. Most patients can be evaluated in
      the office setting utilizing simple testing. Current treatments consist of
      behavioral/lifestyle modification, usually in combination with antimuscarinic
      drug therapy. Improvements in the adverse effect profiles of antimuscarinic drugs
      have positively impacted quality of life. When appropriately evaluated, most
      patients presenting to primary care providers can be effectively treated.

PMID- 21079537
TI  - Lead poisoning from a gunshot wound.
AB  - Lead poisoning from gunshot wounds is unusual. Awareness of this rare but serious
      complication can guide the physician in making a prompt diagnosis. We present a
      case of a 30-year-old male who had a remote history of a gunshot wound in the
      right knee and presented with right knee pain. Plain film showed intrarticular
      invasion of the bullet fragments. He was also found to have microcytic anemia
      with high blood lead levels. Chelation therapy was immediately started, followed
      with surgical removal of the bullet fragments. Lead intoxication is a rare but
      fatal complication of gunshot wounds. After a timely diagnosis, chelation therapy
      should be immediately started.

PMID- 21079536
TI  - Optimizing chronic obstructive pulmonary disease management in primary care.
AB  - Diagnosis of chronic obstructive pulmonary disease (COPD) in primary care is
      complex, as many clinical symptoms are similar to asthma and heart disease, which
      may lead to misdiagnosis and suboptimal disease management. Spirometry is the
      best method for diagnosing COPD and distinguishing between COPD, asthma, and
      cardiovascular diseases. Airway obstruction is fully reversible in asthma, but
      not in COPD, and can be confirmed when the postbronchodilator ratio of forced
      expiratory volume in one second (FEV1) to forced vital capacity (FVC) is <0.7.
      Knowledge of COPD treatment guidelines and a proactive attitude toward disease
      management by primary care physicians are key to improving symptom control and
      patients' quality of life. Identification of the appropriate drug/inhaler
      combination, patient education, training on inhaler use followed by regular
      monitoring, and pulmonary rehabilitation are also vital to successful COPD
      management. This review outlines steps to aid physicians in devising and
      implementing an optimal management plan for COPD patients.

PMID- 21079538
TI  - Intramural gallstones mimicking typical lithiasic cholecystitis.
AB  - Gallstone disease is common in the western population. Intramural gallstones are
      rare, with only a few cases reported in the literature. We present a 30-year-old
      female patient with typical symptoms of cholecystitis. The patient underwent
      laparoscopic cholecystectomy one month later. Dark greenish intramural gallstones
      were identified right after the resection of the gallbladder, and the pathologic
      examination revealed adenomyomatosis of the gallbladder. To our knowledge, this
      is the first report of intramural gallstones presenting with cholecystitis. The
      presence of intramural gallstones is not easily detected during ultrasound
      examination, and does not affect the natural course or treatment of gallstone
      disease.

PMID- 21079539
TI  - Radiation-associated prolactinoma.

PMID- 21079540
TI  - Preoperative fibrinogen plasma concentration is associated with perioperative
      bleeding and transfusion requirements in scoliosis surgery.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: To investigate the
      potential association between fibrinogen, bleeding, and transfusion requirements
      after scoliosis surgery. SUMMARY OF BACKGROUND DATA: Bleeding complications
      during and after orthopedic surgery are associated with increased morbidity and
      mortality. Early identification of patients with increased risk of excessive
      bleeding offers the possibility to initiate countermeasures. Fibrinogen is a key
      protein in the coagulation cascade, and thus a potential biomarker for bleeding
      risk. METHODS: A total of 82 otherwise healthy patients (mean age: 15 +/- 3
      years, 85% girls) undergoing surgery for adolescent idiopathic scoliosis were
      included in the study. Patient variables (age, gender, operation time, and
      thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet
      count, activated partial thromboplastin time [aPTT], prothrombin time [PT], and
      fibrinogen), peroperative and postoperative bleeding volume, and transfusions
      were registered. Correlations between laboratory variables and bleeding volume
      were calculated with Pearson test. Patient variables and laboratory variables
      were compared with Student t test between patients with bleeding volume in the
      upper quartile ("bleeders") and the remaining patients, and between patients with
      extensive transfusion (defined as >2 U of packed red cells) and no or limited
      transfusions (<= 2 U). RESULTS: Mean fibrinogen concentration was 3.0 +/- 0.7 g/L
      (range, 1.3- 4.9). Mean total perioperative bleeding volume was 1552 +/- 1019 mL
      (range, 100-5800 mL). Total bleeding volume correlated significantly with
      preoperative fibrinogen concentration (r = -0.31, P = 0.005) but neither with
      platelet count, aPTT, nor PT (P = 0.61, 0.46, and 0.57, respectively). Bleeders
      had significantly lower preoperative fibrinogen plasma concentration (2.6 +/- 0.6
      vs. 3.1 +/- 0.6 g/L, P = 0.002). Of total, 16% (13/82) of the patients were
      transfused with >2 U of packed red cells. Patients with extensive transfusions
      had significantly lower preoperative fibrinogen plasma concentration (2.5 +/- 0.7
      vs. 3.1 +/- 0.6 g/L, P = 0.002), while preoperative platelet count, aPTT, and PT
      did not differ. CONCLUSION: The results indicate that preoperative fibrinogen
      concentration is a limiting factor for postoperative hemostasis during and after
      scoliosis surgery. Preoperative measurement of fibrinogen concentration provides
      more information about bleeding volume and transfusion requirements than standard
      screening tests.

PMID- 21079541
TI  - Prevalence of neck and low back pain in community-dwelling adults in Spain: a
      population-based national study.
AB  - STUDY DESIGN: Cross-sectional epidemiological study. OBJECTIVE: To determine the
      1-year prevalence of neck pain and low back pain in the Spanish population and
      their association with sociodemographic and lifestyle habits, self-reported
      health status and comorbidity with other chronic disorders. SUMMARY OF BACKGROUND
      DATA: No recent population-based epidemiological studies have estimated the
      prevalence of neck and low back pain in Spain. METHODS: We analyzed data obtained
      from adults aged 16 years or older (n = 29,478) who participated in the 2006
      Spanish National Health Survey, an ongoing, home-based personal interview which
      examines a nation-wide representative sample of civilian noninstitutionalized
      population residing in main family dwellings (household) of Spain. We analyzed
      prevalence data of neck and low back pain and their relationship with socio
      demographic characteristics (sex, age, marital status, educational level,
      occupational status, or monetary income), self-perceived health status, lifestyle
      habits (smoking habit, alcohol consumption, sleep habit, physical exercise, or
      obesity), and the presence of concomitant chronic diseases or symptoms. RESULTS:
      The 1-year prevalence was 19.5% (95% CI: 18.9-20.1) for neck pain and 19.9% (95%
      CI: 19.3-20.5) for low back pain. Both neck pain and low back pain were higher
      among female (26.4% and 24.5%) than male (12.3% and 15.1%). Subjects in the 31 to
      50 years group were 1.5 times (95% CI: 1.3-1.8) more likely to report low back
      pain than participants in the 16 to 30 years group. Individuals reporting neck or
      low back pain showed worse self-reported health status (OR: 4.9, 95% CI: 4.5-5.3
      for neck pain; OR: 4.7, 95% CI: 4.3-5.1 for low back pain) and were more likely
      to complain of depression (OR: 4.3, 95% CI: 3.9-4.7 or OR: 3.6, 95% CI: 3.3-3.9,
      respectively). Further, a strong association between neck and low back pain was
      found (OR: 15.6, 95% CI: 14.2-17.1). Finally, neck pain and low back pain were
      also associated with several other chronic conditions, particularly arthrosis
      (OR: 6.5, 95% CI: 6.0-7.0), and headaches (OR: 4.3, 95% CI: 3.9-4.8) for neck
      pain, and both arthrosis (OR: 5.7, 95% CI: 5.3-6.2), and osteoporosis (OR: 6.3,
      95% CI: 5.6-7.2), for low back pain. CONCLUSION: This Spanish population-based
      survey showed that neck and low back pain are prevalent and highly associated
      between them, more frequent in female (particularly neck pain) and associated to
      worse self-reported health status. Individuals with neck and low back pain were
      more likely than those without pain to have depression and other painful
      conditions, including headache and osteoporosis.

PMID- 21079542
TI  - An examination of outcome measures for pain and dysfunction in the cervical
      spine: a factor analysis.
AB  - STUDY DESIGN: Cross-sectional design. OBJECTIVE: To examine and compare the
      factorial structure of 4 validated neck pain and dysfunction scales. SUMMARY OF
      BACKGROUND DATA: Neck pain and dysfunction is commonly measured using 1 of 4
      validated self-reporting questionnaires: the Neck Disability Index (NDI), the
      Northwick Park Neck Pain Questionnaire (NPQ), the Copenhagen Neck Functional
      Disability Scale (CNFDS), and the Neck Pain and Disability Scale (NPDS). Although
      used interchangeably in the literature, recent studies suggest that the 4 scales
      differ in the number and type of factors that they examine and the weighting of
      these factors. To date, there have been no direct comparisons made of these
      scales when applied simultaneously to the same patient population. METHODS: Data
      were collected from 88 patients with mechanical neck pain who completed all 4
      questionnaires. Exploratory principal components factor analyses were conducted
      to expose the underlying factors within each of the scales. Identified factors
      were examined, characterized, and compared. RESULTS: Factor analysis revealed a
      single factor for the NDI, 2 factors for the NPQ, and 3 factors for both the
      CNFDS and NPDS. Factors identified include neck pain, dysfunction related to
      general activities, neck-specific function, cognition, emotion, and the influence
      of participation restriction on psychosocial functioning. The 3 NPDS factors
      appear to assess the multidimensional nature of neck pain and dysfunction most
      comprehensively. CONCLUSION: When selecting and interpreting a neck pain and
      dysfunction scale, clinicians and researchers are encouraged to take into account
      the factors measured by the NDI, NPQ, CNFDS, and NPDS and their applicability to
      the specific neck patient population under examination. The decision of which
      factors are of greatest interest will influence the selection of an appropriate
      outcome instrument.

PMID- 21079543
TI  - Dynamic response of the idiopathic scoliotic spine to axial cyclic loads.
AB  - STUDY DESIGN: Numerical techniques were used to study the vibration response of
      idiopathic scoliosis patients with single thoracic curve. OBJECTIVE: To analyze
      the dynamic characteristics of the idiopathic scoliotic spine under the whole
      body vibration condition. The influence of the upper body mass was also studied.
      SUMMARY OF BACKGROUND DATA: The relationship between the whole-body vibration and
      the spinal disorders has been investigated using finite element method. However,
      the dynamic response features of the scoliotic spine to the vibration were poorly
      understood. METHODS: The resonant frequencies of the scoliotic spine and the
      effects of the body weight were studied using a finite element model described
      previously. Modal and harmonic analysis was conducted. The amplitudes of 6
      fundamental vertebral movements around the long, coronal and sagittal axis were
      quantified in the frequency range of 1 to 35 Hz. RESULTS: The vibration-induced
      rotation amplitudes of the apex of the thoracic deformity were higher than that
      of the lumbar segments. The apical vertebrae had the greatest rotation amplitudes
      at 2 and 8 Hz, and the largest lateral translation amplitudes at 16 Hz. Vibration
      could cause large lateral flexion amplitudes in the apex of the thoracic
      deformity. The apical vertebrae had the largest side flexion amplitudes at 6 Hz.
      Increasing upper body mass could not change resonant frequency of vibration
      induced lateral translation and rotation around the long axis of the apical
      vertebrae. CONCLUSION: The scoliotic spine is more sensitive to vibration than
      the normal spine. For a patient with single thoracic curve, long-term whole-body
      vibration may do more harm to the thoracic deformity than to the lower lumbar
      segments. Axial cyclic loads applied to an already deformed spine may cause
      further rotational and scoliotic deformity. The patients with idiopathic
      scoliosis are more likely to suffer from vibration-induced spinal disorders than
      those by normal persons.

PMID- 21079544
TI  - Posterior short-segment fixation and fusion in unstable Hangman's fractures.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE.: To introduce the method of C2-C3
      posterior short-segment fixation and fusion in unstable Hangman's fracture and to
      evaluate the clinical effects. SUMMARY OF BACKGROUND DATA: Hangman's fracture can
      be managed by closed reduction and immobilization. However, surgery is usually
      preferable in highly unstable cases and in rigid arthrodesis failure. The outcome
      of surgical treatment for unstable Hangman's fracture has not been thoroughly
      investigated. METHODS: Thirty-five patients with unstable Hangman's fracture were
      treated using C2-C3 posterior short-segment fixation and fusion. Twenty-six cases
      used C2-C3 short-segment pedicle screw fixation. Nine cases used both C2 pedicle
      screw and C3 lateral mass screw short-segment fixation and fusion. C-arm
      fluoroscopy was used for the whole procedure. RESULTS.: All patients were
      observed for an average of 44 months, ranging from 12 to 78 months. There was no
      screw loosening or breakage, nor was there any spinal cord or vertebral artery
      injury intraoperatively. A total of 140 screws were placed, with 70 screws
      inserted into the C2 pedicle, 52 into the C3 pedicle, and 18 into the C3 lateral
      mass. Computed tomography scans indicated 9 screws were placed too close to the
      vertebral artery canal in C2, and 12 screws were too close to the canal in the C3
      pedicle, all without clinical consequences. C3 lateral mass screws were placed
      successfully. Neurologic status improved from C and D to E in all 8 cases. Static
      and dynamic films demonstrated that fusion was achieved in all cases 6 months
      after surgery. No graft or plate-related complications were observed in any
      patients during the entire follow-up period. CONCLUSION: C2-C3 posterior short
      segment fixation and fusion is an effective method for the management of unstable
      Hangman's fracture, proving its value as a technique for achieving solid bony
      fusion combined with a low rate of complications.

PMID- 21079545
TI  - Systemic bioavailability and pharmacokinetics of the doxylamine-pyridoxine
      delayed-release combination (Diclectin).
AB  - BACKGROUND: Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg
      pyridoxine hydrochloride, is the drug combination of choice for the management of
      nausea and vomiting during pregnancy in Canada. However, there is large
      variability in its onset and duration of action among women. To understand and
      improve its effectiveness, the variability in the pharmacokinetics of the
      ingredients in this doxylamine succinate/pyridoxine hydrochloride combination
      must be studied. OBJECTIVES: To determine the pharmacokinetics of DOX and
      pyridoxine after oral administration of two tablets of this drug combination in
      the form of Diclectin and to calculate their respective relative bioavailability
      by comparison with intravenous administration in another population. METHODS:
      Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of
      age were administered two tablets of Diclectin with 240 mL of water under empty
      stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with
      its four active metabolites: pyridoxal, pyridoxal-5'-phosphate (PLP),
      pyridoxamine, and pyridoxamine-5'-phosphate using tandem mass spectrometry. For
      the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted
      for body weight. RESULTS: The mean DOX-AUC0->infinity was calculated to be
      3137.22 +/- 633.57 ng.hr/mL (range, 2056.59-4376.06 ng.hr/mL). The mean PLP-AUC0
      >infinity was calculated to be 5513.10 +/- 2362.35 ng.hr/mL (range, 1572.56
      10,153.77 ng.hr/mL). Based on literature values of the PLP-AUC0->infinity after
      intravenous administration and data from the current study, the relative
      bioavailability of pyridoxine in Diclectin was calculated at 100%. CONCLUSION:
      There was a 2.1-fold variability in the DOX-AUC0->infinity and 6.5-fold
      variability in the PLP-AUC0->infinity after oral administration of 20 mg
      Diclectin. Using literature values and data from the current study, we estimated
      the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual
      differences in metabolism, and not in bioavailability, may be important sources
      of variability that need to be addressed in dosing guidelines.

PMID- 21079546
TI  - Abbott ARCHITECT clinical chemistry and immunoassay systems: digoxin assays are
      free of interferences from spironolactone, potassium canrenoate, and their common
      metabolite canrenone.
AB  - Spironolactone, which is metabolized to canrenone, is often used in combination
      with digoxin. Potassium canrenoate is a similar drug that is also metabolized to
      canrenone. As a result of reported interference of spironolactone, potassium
      canrenoate, and their common metabolite canrenone with digoxin immunoassays, we
      investigated potential interference of these compounds with two relatively new
      digoxin assays for application on ARCHITECT clinical chemistry platforms (cDig,
      particle-enhanced turbidimetric inhibition immunoassay) and ARCHITECT immunoassay
      platforms (iDig, chemiluminescent microparticle immunoassay), both from Abbott
      Diagnostics. When aliquots of drug-free serum pool were supplemented with various
      amounts of spironolactone, potassium canrenoate, and canrenone, no apparent
      digoxin concentration was observed using cDig assay on ARCHITECT c4000, c8000,
      and c16000 or iDig assay on i1000SR and i2000SR analyzers. In addition, we
      observed no false increase in serum digoxin value when aliquots of a digoxin pool
      were further supplemented with various amounts of spironolactone, potassium
      canrenoate, or canrenone. We conclude that both the cDig and iDig assays on the
      ARCHITECT analyzers are free from interferences by spironolactone, potassium
      canrenoate, and canrenone.

PMID- 21079548
TI  - Rejecting minors--it's all in the presentation.

PMID- 21079547
TI  - Urinary cell levels of mRNA for OX40, OX40L, PD-1, PD-L1, or PD-L2 and acute
      rejection of human renal allografts.
AB  - BACKGROUND: The positive costimulatory proteins OX40 and OX40L and negative
      regulatory proteins programmed death (PD)-1, PD ligand 1, and PD ligand 2 have
      emerged as significant regulators of acute rejection in experimental
      transplantation models. METHODS: We obtained 21 urine specimens from 21 renal
      allograft recipients with graft dysfunction and biopsy-confirmed acute rejection
      and 25 specimens from 25 recipients with stable graft function and normal biopsy
      results (stable). Urinary cell levels of mRNAs were measured using real-time
      quantitative polymerase chain reaction assays, and the levels were correlated
      with allograft status and outcomes. RESULTS: Levels of OX40 mRNA (P<0.0001, Mann
      Whitney test), OX40L mRNA (P=0.0004), and PD-1 mRNA (P=0.004), but not the mRNA
      levels of PD ligand 1 (P=0.08) or PD ligand 2 (P=0.20), were significantly higher
      in the urinary cells from the acute rejection group than the stable group.
      Receiver operating characteristic curve analysis demonstrated that acute
      rejection is predicted with a sensitivity of 95% and a specificity of 92% (area
      under the curve=0.98, 95% confidence interval 0.96-1.0, P<0.0001) using a
      combination of levels of mRNA for OX40, OX40L, PD-1, and levels of mRNA for the
      previously identified biomarker Foxp3. Within the acute rejection group, levels
      of mRNA for OX40 (P=0.0002), OX40L (P=0.0004), and Foxp3 (P=0.04) predicted acute
      rejection reversal, whereas only OX40 mRNA levels (P=0.04) predicted graft loss
      after acute rejection. CONCLUSION: A linear combination of urinary cell levels of
      mRNA for OX40, OX40L, PD-1, and Foxp3 was a strong predictor of acute rejection
      in human renal allograft biopsies. This prediction model should be validated
      using an independent cohort of renal allograft recipients.

PMID- 21079549
TI  - Centre-specific variation in corneal transplant outcomes in the United Kingdom.
AB  - BACKGROUND: To examine the influence of center or surgeon transplant workload on
      corneal transplant outcome. METHODS: In this database study, centers were
      categorized as high or low volume if registering more than 50 and less than 10
      corneal transplants per year, respectively; surgeons were categorized as high or
      low volume if registering more than 30 and less than 10 transplants per year,
      respectively. The participants were patients aged at least 17 years receiving a
      first penetrating keratoplasty for keratoconus, Fuchs' endothelial disease, or
      pseudophakic corneal edema in a 7-year period from 1999 in (1) high-volume
      (n=1724) and low-volume (n=2131) centers and (2) under care of high-volume
      (n=1332) and low-volume (n=1949) surgeons. Main outcome measures were (1) graft
      survival at 5 years and (2) 2-year posttransplant best-corrected and day-to-day
      visual acuity and astigmatism. RESULTS: No significant difference in graft
      survival was found according to center or surgeon workload. Statistically
      significantly better day-to-day visual acuity was found only in patients with
      Fuchs' endothelial disease managed by high-volume surgeons (20/40 or better in
      50% vs. 42% for low-volume surgeons). There was statistically significantly
      better best-corrected visual acuity in high-volume centers for Fuchs' endothelial
      disease and pseudophakic corneal edema and for high-volume surgeons in all
      disease groups. CONCLUSIONS: Based on this national transplant cohort, when
      analyzed according to center volume or surgeon transplant workload, there is no
      variation in graft survival and only minor variation in transplant functional
      outcome.

PMID- 21079550
TI  - Is the increase in DCD organ donors in the United Kingdom contributing to a
      decline in DBD donors?
AB  - INTRODUCTION: Organ donation after brain death (DBD) has declined in the United
      Kingdom, whereas donation after cardiac death (DCD) has increased markedly. We
      sought to understand the reasons for the decline in DBD and determine whether the
      increase in DCD was a major factor. METHODS: The UK Transplant Registry was
      analyzed to determine trends in organ donation. Data from the "Potential Donor
      Audit," an audit of all patients younger than 76 years who died in
      noncardiothoracic UK intensive care units, was analyzed to identify trends in
      clinical demographics and management and to determine whether potential donors
      (DBD and DCD) were identified and appropriate steps were taken to enable organ
      donation. RESULTS: There were 7589 (12.8 per million of population [pmp])
      deceased organ donors in the United Kingdom from 1999 to 2009. The total number
      of deceased donors increased by 16% (to 14.9 pmp), but DBD donors decreased from
      744 to 612, and the overall increase in donors was due to an 8-fold increase in
      DCD donors (33 in 1999 to 2000, 288 in 2008 to 2009). Analysis of the Potential
      Donor Audit over the 5-year period 2004 to 2005 to 2008 to 2009 showed that the
      number of patients dying in intensive care units who were possibly brain stem
      dead (comatose, apparently apnoeic with unresponsive pupils) decreased from 1929
      in 2004 to 2005 to 1495 in 2008 to 2009 (22.5% reduction). The proportion of
      potential DBD donors who became donors increased from 45% to 51%. CONCLUSION:
      There is no evidence that the increase in DCD donors has contributed directly to
      the decline in DBD, which reflects a decrease in the number of patients with
      brain death.

PMID- 21079551
TI  - Anti-BK virus mechanisms of sirolimus and leflunomide alone and in combination:
      toward a new therapy for BK virus infection.
AB  - BACKGROUND: Human BK polyomavirus is the causative agent of BK nephropathy which
      is now the leading cause of early renal graft loss. Although no randomized
      clinical trials have supported this therapy, reduction of immunosuppressive drugs
      is the current BK nephropathy treatment. We hypothesized that inhibition of the
      intracellular protein kinase pathways activated by BK virus may be a more
      effective therapeutic strategy than reduction of immunosuppression. METHODS AND
      RESULTS: Four days after infection of renal epithelial cells lines CCD1103,
      CCD1105 and human primary tubular epithelial cells with BK virus, we found
      increased phosphorylation of 3'-phosphoinositide-dependent kinase-1 (PDK-1), the
      protein kinase Akt (Akt), mammalian target of rapamycin (mTOR), and 70 kDa
      ribosomal protein S6 kinase (p70S6K). To inhibit this pathway, we used sirolimus,
      which repressed p70S6K phosphorylation and reduced BK virus large T antigen
      expression in a dose-dependent manner. We then used the tyrosine kinase inhibitor
      leflunomide (using the active metabolite A77 1726), which decreased PDK1 and Akt
      phosphorylation and inhibited BK virus genome replication and early gene
      expression. The combination of sirolimus and leflunomide inhibited BK virus
      genome replication, large T antigen expression, PDK1, Akt, mammalian target of
      rapamycin, and p70S6K phosphorylation. CONCLUSIONS: On the basis of these
      results, we suggest that inhibition of protein kinase pathways with a combination
      of sirolimus and leflunomide may be an effective therapy for BK virus
      reactivation. Because both sirolimus and leflunomide possess immunosuppressive
      activity, combination therapy may reduce BK pathogenesis while maintaining
      appropriate transplant immunosuppression.

PMID- 21079552
TI  - Prevention of chronic renal allograft rejection by soluble CD83.
AB  - BACKGROUND: Recombinant human soluble CD83 had previously exhibited significant
      immunosuppressive properties that involved interference with dendritic cell
      maturation in both mouse and humans, inhibition of autoimmunity in mice, and
      induction of antigen-specific mouse cardiac allograft tolerance when used in
      combination with other immunosuppressive drugs. Our current research focus turned
      to examining the effects of peritransplant soluble CD83 (sCD83) administration on
      prevention of chronic renal allograft rejection. METHODS: Fisher344-to-Lewis
      orthotopic rat renal transplants were performed with sequential recipient killing
      on postoperative days (PODs) 2, 14, and 140 to examine both the acute and chronic
      effects of peritransplant sCD83 treatment in rat recipients. RESULTS: Recipients
      treated with sCD83 exhibited a marked decrease in IgM and IgG deposition in the
      graft and antidonor antibody levels in the circulation, as early as POD14 and
      persisting until POD140. sCD83 treatment also reduced the infiltration of T cells
      and monocytes into the graft tissue and inhibited intragraft expression of MyD88
      and inflammatory cytokine levels during the observation period. sCD83-treated
      grafts demonstrated normal histology beyond POD140, including dramatic reductions
      in tubular atrophy and interstitial fibrosis compared with untreated recipients.
      CONCLUSION: We have demonstrated that peritransplant treatment with recombinant
      sCD83 attenuates both innate and adaptive immune responses and leads to
      prevention of chronic rejection in a rat renal transplant model. Because sCD83 is
      of human origin, the therapeutic approach used in our rodent transplant model
      holds significant promise for clinical transplantation.

PMID- 21079555
TI  - Staff flu vaccination: A patient safety necessity?

PMID- 21079553
TI  - Predicting HLA class II alloantigen immunogenicity from the number and
      physiochemical properties of amino acid polymorphisms.
AB  - BACKGROUND: We have shown previously that human leukocyte antigen (HLA) class I
      immunogenicity can be predicted by the number, position, and physiochemical
      differences of polymorphic amino acids (AAs). We have now modeled the structural
      and physiochemical polymorphisms of HLA class II alloantigens and correlated
      these with humoral alloimmunity in sensitized patients awaiting kidney
      transplantation. METHODS: Sera obtained from 30 patients with high levels of IgG
      HLA-specific antibodies were screened using single-antigen HLA antibody detection
      beads. A computer program was developed to determine the number of AA mismatches
      (after interlocus and intralocus subtraction) and their hydrophobicity and
      electrostatic mismatch score for each mismatched HLA-DR and -DQ specificity.
      Regression methods were used to compare these variables with the occurrence and
      magnitude of alloantibody responses. RESULTS: HLA-specific antibody was detected
      against 879 (55%) of 1604 mismatched HLA specificities evaluated. There was a
      strong correlation between increasing number of AA mismatches and the occurrence
      (P<0.001, odds ratio 3.85 per AA) and magnitude of alloantibody responses
      (P<0.001); only 6% of alloantigens with 0 to 2 mismatched AA-induced alloantibody
      (median fluorescence intensity 37) compared with 82% of alloantigens with more
      than or equal to 20 mismatched AAs (median fluorescence intensity 9969).
      Hydrophobicity and electrostatic mismatch scores also correlated closely with
      alloantibody response (P<0.001), but neither variable had independent predictive
      value over the number of AA mismatches alone. CONCLUSION: Differences in the
      number of polymorphic AA mismatches and their physiochemical properties for a
      given recipient HLA type are strong predictors of class II alloantigen
      immunogenicity and alloantibody response before kidney transplantation.

PMID- 21079556
TI  - Treating urinary incontinence in older women.
AB  - Urinary incontinence is a common hidden problem which affects up to 30% of older
      people (Nazarko, 2008). It is often ignored or not treated effectively and often
      women suffering with urinary incontinence do not present to primary care
      practitioners, as they perceive it as an inevitable consequence of ageing. This
      article aims to discuss the types of urinary incontinence and treatments
      available to older women presenting with urinary incontinence in primary care.

PMID- 21079557
TI  - The role of community nurses in promoting self-care.

PMID- 21079558
TI  - Implications of the 2010 rheumatoid arthritis classification criteria.

PMID- 21079559
TI  - Palliative care based on need not diagnosis; challenges for nurses.

PMID- 21079560
TI  - Principles of good evidence giving.
AB  - With increased regulation and litigation in the health-care sector, appearing in
      court is becoming an almost routine part of a district nurse's role. A review of
      local newspapers shows that in the last 4weeks alone district nurses around the
      UK have given evidence in no fewer than ten different cases that have involved
      the coroners' court, county court and magistrates' court. The prospect of
      appearing in court or giving evidence at fitness to practice hearings remains a
      daunting one. The process is still largely adversarial and cross examination is a
      hostile experience. This article highlights the principles of good evidence.

PMID- 21079561
TI  - The use of professional portfolios and profiles for career enhancement.
AB  - Since 1995, registered nurses and midwives have been obliged to develop and
      maintain a professional portfolio of evidence reflecting the learning activities
      that they have undertaken and how these have informed and influenced their
      practice. The aim of this article is to demonstrate that rather then just a
      retrospective account of continuing professional development activities, a
      portfolio can be used as a vehicle for engaging in self-assessment and personal
      development planning. Possible structures and type of evidence are explored and
      portfolios in the context of gaining accreditation for prior experiential
      learning, and in particular for those nurses in advanced clinical roles, are
      discussed.

PMID- 21079562
TI  - Implementing KSF competency testing in primary care. Part 2: Evaluation of the
      pilot of an appraisal tool.
AB  - Assessment of competence is a way of measuring if staff are fit for purpose.
      Clinical competences, against which performance is measured, have been developed
      in a wide range of clinical settings in recent years (Department of Health (DH),
      2008). Several trusts also operate an assessment centre in the recruitment and
      selection of staff, and these frequently involve competency testing in order to
      be certain that their new recruits are fit for their post. Agenda for Change (DH,
      2004a) firmly links pay to the competences expressed in the Knowledge and Skills
      Framework (DH, 2004b; c) yet the KSF has not been implemented in all trusts. In
      part 1 of this article (Bentley and Dandy-Hughes, 2010), the process of Southwark
      PCT's competency project was described. This involved the process of writing
      measurable, manageable competences from the KSF, in order to develop staff to be
      fit for purpose. Part 2 evaluates the use of the appraisal tool that was
      developed from the KSF, and examines the role of the nurse consultant in
      education who led the competency project.

PMID- 21079563
TI  - Liberating new talents: an innovative pre-registration community-focused adult
      nursing programme.
AB  - The drive for a more community-focused approach to pre-registration nursing
      education as identified in Modernising Nursing Careers, (Department of Health,
      2006a) has continued to gather momentum. The research literature identifies that
      the community context impacts significantly on care delivery, with student nurses
      often missing the underlying complexities of working in this context; focusing on
      the task in hand rather than the broader landscape of care (Carr, 2004). In 2008,
      a community focused pre-registration adult nursing degree pathway was started at
      Canterbury Christ Church University (CCCU), to prepare a cohort of 16 nursing
      students to work in the community and general practice setting at the point of
      registration. Placement learning has been focused within general practice and
      community through a hub and spoke approach to enable students to develop a deep
      understanding of the complexities of care in this setting with particular
      reference to the management of risk and unpredictability. The pilot is being
      formally evaluated with a particular emphasis on the meaning and relevance of
      practice learning within these settings. The emerging data will not only provide
      evidence to promote the community and general practice agenda within pre
      registration curricula, but help to clarify the essential skills and knowledge
      required to prepare students nurses for working in these settings.

PMID- 21079564
TI  - Mindfulness: me-time counts.

PMID- 21079566
TI  - MimoDB: a new repository for mimotope data derived from phage display technology.
AB  - Peptides selected from phage-displayed random peptide libraries are valuable in
      two aspects. On one hand, these peptides are candidates for new diagnostics,
      therapeutics and vaccines. On the other hand, they can be used to predict the
      networks or sites of protein-protein interactions. MimoDB, a new repository for
      these peptides, was developed, in which 10,716 peptides collected from 571
      publications were grouped into 1,229 sets. Besides peptide sequences, other
      important information, such as the target, template, library and complex
      structure, was also included. MimoDB can be browsed and searched through a user
      friendly web interface. For computational biologists, MimoDB can be used to
      derive customized data sets and benchmarks, which are useful for new algorithm
      development and tool evaluation. For experimental biologists, their results can
      be searched against the MimoDB database to exclude possible target-unrelated
      peptides. The MimoDB database is freely accessible at http://immunet.cn/mimodb/.

PMID- 21079567
TI  - Towards the development of synthetic routes using theoretical calculations: an
      application of in silico screening to 2,6-dimethylchroman-4-one.
AB  - This study describes an attempt to develop a synthetic route using theoretical
      calculations, i.e., in silico synthesis route development. The KOSP program
      created four potential synthetic routes for generating 2,6-dimethylchroman-4-one.
      In silico screening of these four synthetic routes was then performed. In silico
      screening involves theoretical analysis of synthetic routes prior to actual
      experimental work. A synthetic route using the Mitsunobu reaction had already
      been reported by Hoddgets et al. Theoretical investigations were also conducted
      on two S(N)Ar reactions as well as a Michael reaction before they were examined
      experimentally. In silico screening using DFT calculations indicated that only
      the Michael reaction was likely to produce the target. Experimental work
      confirmed that the target was obtained in a yield of 76.4% using the Michael
      reaction. The other two routes, except for the Mitsunobu reaction, failed to
      generate the target. Our results demonstrate that theoretical calculations can be
      used to narrow down the number of experiments that need to be conducted when
      developing novel synthetic routes.

PMID- 21079565
TI  - Radiolabeled small molecule protein kinase inhibitors for imaging with PET or
      SPECT.
AB  - Imaging protein kinase expression with radiolabeled small molecule inhibitors has
      been actively pursued to monitor the clinical potential of targeted therapeutics
      and treatments as well as to determine kinase receptor density changes related to
      disease progression. The goal of the present review is to provide an overview of
      the breadth of radiolabeled small molecules that have been synthesized to target
      intracellular protein kinases, not only for imaging in oncology, but also for
      other areas of interest, particularly the central nervous system. Considerable
      radiotracer development has focused on imaging receptor tyrosine kinases of
      growth factors, protein kinases A, B and C, and glycogen synthase kinase-3beta.
      Design considerations, structural attributes and relevant biological results are
      summarized.

PMID- 21079568
TI  - Catalytic asymmetric synthesis of both enantiomers of 4-substituted 1,4
      dihydropyridines with the use of bifunctional thiourea-ammonium salts bearing
      different counterions.
AB  - Organoammonium salts composed of a Bronsted acid and an anilinothiourea promoted
      the Michael addition of beta-keto esters and alpha,beta-unsaturated aldehydes in
      the presence of primary amines to give functionalized 1,4-dihydropyridines
      enantioselectively. With the use of the different Bronsted acids such as DFA and
      HBF(4) with the same bifunctional thiourea, both enantiomers of 4-substituted 1,4
      dihydropyridine were synthesized from the same starting materials.

PMID- 21079569
TI  - Synthesis and properties of chiral thioureas bearing an additional function at a
      remote position tethered by a 1,5-disubstituted triazole.
AB  - The synthesis and properties of multifunctional thioureas bearing a variety of
      functional groups at a position remote from the thiourea moiety are described. A
      1,5-disubstituted triazole tether connected with a thiourea and another
      functional group was synthesized via ruthenium catalyzed Huisgen cycloaddition.
      We demonstrate the utility of the synthetic thioureas as asymmetric catalysts and
      probes for the mechanistic elucidation of the course of the Michael reaction of
      an alpha,beta-unsaturated imide.

PMID- 21079570
TI  - Synthesis, structures and properties of Cu(II) and Mn(II) complexes with 1,10
      phenanthroline-2-carboxylic acid and 2,2'-bipyridine ligands.
AB  - Four new 2,2'-bipyridine and 1,10-phenanthroline complexes, namely
      [Mn(phenca)(2)].(H(2)O)(2) (1), [Cu(4)(phen)(4)(OH-)(4)(H(2)O)(2)](DMF)(4)(ClO(4)
      )(4)(H(2)O) (2), [Cu(2)(2,2-bipy)(2)(C(2)O(4)2-)(H(2)O)(2)(NO(3))(2)] (3) and
      [Cu(2,2-bipy)(2)(ClO(4)-)](ClO(4)-) (4) (2,2'-bpy = 2,2'-bipyridine, Hphenca =
      1,10-phenanthroline-2-carboxylic acid) have been synthesized by a hydrothermal
      reaction. The products were characterized by elemental analysis, infrared
      spectroscopy and X-ray crystal diffraction. While strong hydrogen bonds play
      central roles in the formation of the 3D structure, the combined influence of the
      weak interactions such as pi...pi interactions is also evident in the structures.
      A preliminary investigation on the ion exchange properties of the complexes is
      presented.

PMID- 21079571
TI  - [Innovative genetic, clinical and endocrinologic aspects in young females
      affected by premature ovarian insufficiency].
AB  - AIM: Heterogeneity premature ovarian insufficiency (POI) is one of the reasons
      why there are different causes that contribute in determining this type of
      hormonal disorder. Although the causes have already been established for many
      types of premature ovarian failure, are still uncertain causes in most cases of
      idiopathic forms, despite the description of several candidate genes, including
      BMP-15 gene. The gene under study is precisely the BMP-15, which is part of the
      superfamily of Transforming Growth Factors-beta or the TGF-beta, which also
      belong to the growth differentiation factors (GDFs). METHODS: This study examined
      a sample of Sicilian women suffering from POI, carefully selected according to
      their age, since in these cases, the genetic factor probably has a greater
      impact. RESULTS AND CONCLUSION: Identify a mutant gene that causes ovarian
      failure may be important to make a diagnosis that can predict the possible future
      development of the disease. The outcome of the studies, however, has not found
      the gene in question, but it is hypothesized that this may be a direct
      consequence of the limited amount of women that was done the study, a case which
      may be rebutted by increasing the number of patients.

PMID- 21079572
TI  - [Short-term effect of an estroprogestin containing ethinylestradiol 20 mcg +
      drospirenone 3 mg in 24+4 regimen at hormonal and cutaneous level in ovarian
      hyperandrogenism].
AB  - AIM: evaluate the efficacy of an estroprogestin EP containing 20 mcg
      ethinilestradiol (EE) and 3 mg drospirenone (DRSP) in the treatment of
      hyperandrogenism. METHODS: In this study, twenty hyperandrogenic patients were
      treated with an EP containing EE 20 mcg and DRSP 3 mg in 24+4 regimen for three
      months. Skin evaluation was performed both quantitatively and qualitatively.
      RESULTS AND CONCLUSION: This EP combination showed, after a short-term treatment
      (three months) to decrease significantly seborrhea, acne, and circulating
      androgens (testosterone, deidroepiandrosterone sulphate, and androstenedione),
      while increased sex hormone binding globulin levels. Moreover, this EE 20
      mcg/DRSP 3mg EP combination changed some parameters of skin quality, increasing
      corneometry (a parameter related to skin hydration), and reduced trans epidermal
      water loss (TEWL, a parameter related to skin evaporation), and erythema (a
      parameter related to skin inflammation). These results could be taken into
      account in individualizing the treatment of hyperandrogenic patients.

PMID- 21079573
TI  - Impact of cafedrine/theodrenaline (Akrinor(r) ) on therapy of maternal
      hypotension during spinal anesthesia for Cesarean delivery: a retrospective
      study.
AB  - AIM: Maternal hypotension is the most frequent complication in spinal anesthesia
      for Cesarean delivery. Malperfusion of the foetus and nausea and vomiting of the
      mother are hallmarks of maternal hypotension. In this retrospective data analysis
      and anesthesia protocols we have investigated to explore the effects of
      therapeutic interventions for hypotension with cafedrine/theodrenaline
      (Akrinor(r) ) during spinal anesthesia for elective Cesarean section. METHODS: In
      a retrospective study anesthesia charts of 173 parturients undergoing spinal
      anesthesia for Cesarean delivery with 10mg hyperbaric bupivacaine + 5 ug
      sufentanil were reviewed for 30 min after onset of hypotension with respect to
      blood pressure, heart rate, respiration rate, as well as APGAR scores and
      umbilical arterial pH. Maternal data were compared to baseline values recorded
      and documented immediately before placing the spinal anesthesia in the operating
      room. The cohort was divided into two groups according to their hemodynamic
      response to spinal anesthesia: 117 parturients had a drop of systolic blood
      pressure to <120 mmHg or <80% of baseline blood pressure and were therefore
      treated with Akrinor(r) (cafedrine/theodrenaline; treatment group); 56 patients
      remained within the specified limits (non-treatment group). Maternal
      cardiovascular parameters and newborn outcome between the groups were compared.
      RESULTS: Both groups were comparable with regard to baseline characteristics. In
      the treatment group one minute after the first application of cafedrine (43
      mg)/theodrenaline (2.2 mg) mean systolic blood pressure raised from 108.6 mmHg to
      117.2 mmHg (P=0.0004), mean of maximal changes of systolic blood pressure after
      the first application of Akrinor(r) was 21.3 mmHg. Blood pressure levels of the
      non-treatment group were regained in the treatment group 8 min after hypotension
      onset and remained at that level until the end of 30 min observation. No
      clinically relevant changes of heart rate were detectable. While mean APGAR score
      one minute post partum was significantly higher in the treatment group (8.9+/-1.2
      vs. 8.4+/-1.1 P=0.043), mean umbilical arterial cord pH was 7.3+/-0.1 and APGAR
      scores 5 and 10 minutes postpartum did not differ significantly. CONCLUSION: The
      results of this study confirm a rapid and sustained increase in blood pressure
      after application of Akrinor(r) for treatment of sympathicolysis induced
      hypotension. No negative impact of Akrinor(r) on umbilical arterial cord pH and
      APGAR scores was observed.

PMID- 21079574
TI  - [Effects of inositol on oocyte quality in patients affected with polycystic ovary
      syndrome].
AB  - AIM: Polycystic ovary syndrome is the most common cause of chronic anovulation
      infertility in women in fertile period. The supplementation of inositol, due to
      its ability to increase insulin sensitivity, improves the oocytes' quality and
      increase the number of oocytes collected after ovarian stimulation in patients
      undergoing IVF (In Vitro Fertilization). The aim of our study is to determine the
      effects of myo-inositol on oocyte's quality on a sample of women with polycystic
      ovary syndrome. METHODS: The patients were divided into two groups: patients of
      Group A intook 2 g of myo-inositol + 400 MUg of folic acid 2 times a day,
      continuously for 3 months, while Group B only 400 MUg of folic acid. RESULTS AND
      CONCLUSION: At the end of treatment, the number of follicles of diameter >15 mm,
      visible at ultrasound during stimulation, and the number of oocytes recovered at
      the time of pick-ups were found to be significantly greater in the group treated
      with myo-inositol, so as the average number of embryos transferred and embryo
      Grade G1. Significantly reduced was the average number of immature oocytes
      (vesicles germ and degenerated oocytes) too.

PMID- 21079575
TI  - Gestational diabetes and fetal growth acceleration: induction of labour versus
      expectant management.
AB  - AIM: The aim of the study was to compare elective induction of labour at 38 weeks
      versus expectant management in A1 and A2 gestational diabetes (GDM) pregnancies
      with fetal growth acceleration. Primary outcome of the study was C-section (CS)
      rate, while secondary outcomes were macrosomia incidence and adverse perinatal
      outcomes. METHODS: A retrospective cohort study was carried out. Data were
      collected between 1996 and 2006 and evaluated through patients' records analysis.
      Differences between the two study groups were investigated using non-parametric
      tests for continuous variables and chi2 test for categorical ones. RESULTS: There
      was no significant difference between induction and expectant management in terms
      of caesarean section rate. A trend favoring women in the induction group in terms
      of incidence of macrosomia and neonatal outcomes was identified, but results were
      not statistically significant. CONCLUSION: Labour induction at 38 weeks in GDM
      patients with fetal growth acceleration does not seem to determine an increased
      incidence of C-section in comparison to expectant management, particularly in
      case of maternal obesity.

PMID- 21079576
TI  - Role and application of hysterosalpingography and Fallopian tube recanalization.
AB  - AIM: The prevalence of infertility in the United States is 15-20% and this
      condition represents an important medical problem. The purpose of this work was
      to evaluate therapeutical efficacy of 2 consecutive hysterosalpingography (HSG)
      followed each other after 4 week compared with the fallopian tube recanalization
      (FTR). METHODS: Two groups of 80 patients paired for mean age and age range (age
      range, 23-37 years; mean age, 30 years), were assessed for pregnancy rate (two
      year follow-up) by using two consecutive HSG in one group and HSG and tube
      recanalization in the second group. Pain perception and dose delivered were
      assessed. Statistical analysis was performed to evaluate significant differences
      between the two approaches. RESULTS: Pregnancy rate after TFR was 51% whereas
      pregnancy rate after two consecutive HSG was 31.3% (P= 0.016; OR 2.31) and all
      the pregnancies were observed in those women that showed a positive variation in
      second HSG with a pregnancy rate of 47% (P=0.776; OR=1.18). In one case a serious
      complication was observed (1.25%): a tubal perforation. Minor bleeding sometimes
      lasted for as long as 48 h but never required any medical treatment. Pain
      assessment and dose delivered were statistically different by using these two
      methods (P= 0.027 and P<0.001, respectively) CONCLUSION: Therapeutical efficacy
      of two consecutive HSG followed each other after four week compared with the FTR
      are similar when the second HSG shows the presence of Fallopian tube patency.

PMID- 21079577
TI  - MicroRNAs in breast cancer pathogenesis.
AB  - Micro RNAs (miRNAs) are small non-coding RNAs which regulate fundamental cellular
      and developmental processes at the transcriptional and translational level. In
      breast cancer, expression of miRNAs is frequently dysregulated. Both tumor
      suppressor activity and oncogenic properties have been assigned to specific
      miRNAs, which modulate virtually all relevant stages of breast cancer
      progression, including tumor cell proliferation, apoptosis resistance, cancer
      cell migration, invasiveness and metastasis, tumor angiogenesis and cancer stem
      cell self-renewal. miRNA expression has been studied by microarray profiling,
      bead-based technologies and quantitative real-time PCR in archived formalin-fixed
      paraffin-embedded tumor specimens as well as blood and serum samples, allowing to
      identify specific miRNAs as novel diagnostic, prognostic and predictive markers.
      Moreover, the investigation of single nucleotide polymorphisms both in putative
      miRNA binding sites in the 3'UTRs of target genes, as well as in miRNA-endocing
      genes have revealed their diagnostic potential. In vitro experiments employing
      established breast cancer cell lines and in vivo xenograft studies have
      demonstrated the efficacy of oligonucleotide-based overexpression and inhibitor
      approaches of miRNA-targeted experimental therapies. Numerous studies have
      identified specific targets of miRNA action in breast cancer, including the
      established markers Her2/neu and ERalpha, TP53, and markers of angiogenesis. The
      future application of locked-nucleic acid miRNA inhibitors, and synergistic
      approaches involving conventional breast cancer therapeutics opens up promising
      new perspectives in breast cancer therapy.

PMID- 21079579
TI  - Breast cancer during pregnancy: a literature review.
AB  - Breast cancer during pregnancy is relatively uncommon. However, the incidence is
      expected to increase as more women delay childbearing. A challenging situation
      emerges for all persons involved - patient, family and medical care workers -
      since two lives are at risk with contradicting priorities. Breast cancer
      treatment is possible during pregnancy. The treatment plan needs to adhere as
      closely as possible to standardised protocols for nonpregnant patients, with some
      considerations to minimize fetal exposure and risks. This concerns mainly
      limiting radiation exposure and timing of chemotherapy to start in the second
      trimester. The prognosis of pregnant women does not seem to differ from that of
      nonpregnant patients when matched for age and stage of the disease. This
      literature review concentrates on the diagnosis, treatment and outcome of
      patients diagnosed with breast cancer during pregnancy.

PMID- 21079578
TI  - Extranuclear signaling by estrogen: role in breast cancer progression and
      metastasis.
AB  - The estrogen receptor (ERa) is implicated in the progression of breast cancer.
      Hormonal therapies which block ER functions or local and systemic estrogen
      production are currently used to treat ERa positive breast cancer. Hormonal
      therapy shows beneficial effects, however, initial or acquired resistance to
      endocrine therapies frequently occurs, and tumors recur as metastasis. Emerging
      evidence suggests in addition to exerting its well-studied nuclear functions, ERa
      also participates in extranuclear signaling that involve growth factor signaling
      components, adaptor molecules and the stimulation of cytosolic kinases. ERa
      extranuclear pathways have the potential to activate gene transcription, modulate
      cytoskeleton, and promote tumor cell proliferation, survival, and metastasis.
      Cytoplasmic/membrane ERa is detected in a subset of breast tumors and expression
      of extranuclear components ERa is deregulated in tumors. The extranuclear actions
      of ER are emerging as important targets for tumorigenic and metastatic control.
      Inhibition of ERa extranuclear actions has the potential to prevent breast tumor
      progression and may be useful in preventing ERa positive metastasis. In this
      review, we summarize the results of recent research into the role of ERa mediated
      extranuclear actions in breast tumorigenesis and metastasis.

PMID- 21079580
TI  - New prognostic and predictive factors in breast cancer.
AB  - There are two major questions regarding systemic therapy of breast cancer:
      Firstly, which patients should be treated, and secondly, how should these
      patients be treated? Prognostic factors aim to foresee the outcome of patients
      irrespective of treatment while predictive factors intend to assess the outcome
      of patients receiving a certain systemic therapy and thus are intimately
      associated with sensitivity or resistance to therapy. Ideally, a predictive
      factor is also a therapeutic target as it is the case with estrogen receptor (ER)
      or HER-2. In order to avoid over- as well as under-treatment, it is advisable to
      select the appropriate treatment strategy on the basis of a careful risk
      assessment for each individual patient. Additionally to time-honoured
      clinicopathological factors additional prognostic factors like urokinase-type
      plasminogen activator (uPA)/plasminogen activator inhibitor 1 (PAI-1) or
      multiparameter gene-expression analyses have shown promising results especially
      in node-negative breast cancer. These multigene profiles offer new insights in
      breast cancer biology, like the important role of the tumor-associated immune
      system. ER, HER-2 and potentially newer prognostic factors like epithelial cell
      adhesion molecule (Ep-CAM) bridge the gap from prognosis to prediction and serve
      as therapeutic targets. This should allow us to quantify the risk of progression
      in each individual patient and tailor treatment accordingly, leading to a more
      personalized treatment recommendation.

PMID- 21079583
TI  - Hypertension as a maladaptive "fight-or-flight" response?: confirmatory molecular
      genetic evidence from the human catecholamine biosynthetic pathway.

PMID- 21079581
TI  - Isolation of alveolar epithelial type II progenitor cells from adult human lungs.
AB  - Resident stem/progenitor cells in the lung are important for tissue homeostasis
      and repair. However, a progenitor population for alveolar type II (ATII) cells in
      adult human lungs has not been identified. The aim of this study is to isolate
      progenitor cells from adult human lungs with the ability to differentiate into
      ATII cells. We isolated colony-forming cells that had the capability for self
      renewal and the potential to generate ATII cells in vitro. These undifferentiated
      progenitor cells expressed surface markers of mesenchymal stem cells (MSCs) and
      surfactant proteins associated with ATII cells, such as CD90 and pro-surfactant
      protein-C (pro-SP-C), respectively. Microarray analyses indicated that
      transcripts associated with lung development were enriched in the pro-SP
      C(+)/CD90(+) cells compared with bone marrow-MSCs. Furthermore, pathological
      evaluation indicated that pro-SP-C and CD90 double-positive cells were present
      within alveolar walls in normal lungs, and significantly increased in ATII cell
      hyperplasias contributing to alveolar epithelial repair in damaged lungs. Our
      findings demonstrated that adult human lungs contain a progenitor population for
      ATII cells. This study is a first step toward better understanding of stem cell
      biology in adult human lung alveoli.

PMID- 21079584
TI  - Epithelium-specific ETS-1: a counter-regulatory factor against vascular
      dysfunction and inflammation.

PMID- 21079587
TI  - Grand challenge commentary: Informative diagnostics for personalized medicine.
AB  - Some of the most celebrated triumphs of chemical biology are molecularly targeted
      therapeutics to combat human disease. However, a grand challenge looms as
      informative diagnostic strategies must be developed to realize the full impact of
      these promising pharmaceutical agents.

PMID- 21079586
TI  - A decade of chemical biology.
AB  - With insights from a panel of experts, the Nature Chemical Biology editors
      examine the evolution and current era of chemical biology.

PMID- 21079588
TI  - Grand challenge commentary: Transforming biosynthesis into an information
      science.
AB  - Engineering biosynthetic pathways to natural products is a challenging endeavor
      that promises to provide new therapeutics and tools to manipulate biology.
      Information-guided design strategies and tools could unlock the creativity of a
      wide spectrum of scientists and engineers by decoupling expertise from
      implementation.

PMID- 21079589
TI  - Grand challenge commentary: Accessing new chemical space for 'undruggable'
      targets.
AB  - The synthesis and biological annotation of small molecules from underexplored
      chemical space will play a central role in the development of drugs for
      challenging targets currently being identified in frontier areas of biological
      research such as human genetics.

PMID- 21079591
TI  - Grand challenge commentary: The chemistry of a dynamic genome.
AB  - In the postsequencing era, chemical biology is uniquely situated to investigate
      genomic DNA alterations arising through epigenetic modifications, genetic
      rearrangements or active mutation. These transformations significantly expand
      nature's diversity and may profoundly alter our view of DNA's coding potential.

PMID- 21079590
TI  - Grand challenge commentary: RNA epigenetics?
AB  - Post-transcriptional RNA modifications can be dynamic and might have functions
      beyond fine-tuning the structure and function of RNA. Understanding these RNA
      modification pathways and their functions may allow researchers to identify new
      layers of gene regulation at the RNA level.

PMID- 21079592
TI  - Grand challenge commentary: Beyond discovery: probes that see, grab and poke.
AB  - Chemical biology is now able to discover molecules that manipulate virtually any
      biological target or process. It remains a grand challenge to leverage these
      molecules into useful probes that can be used to address unsolved problems in
      biology.

PMID- 21079593
TI  - Grand challenge commentary: Synthetic immunology to engineer human immunity.
AB  - Rationally designing new strategies to control the human immune response stands
      as a key challenge for the scientific community. Chemical biologists have the
      opportunity to address specific issues in this area that have important
      implications for both basic science and clinical medicine.

PMID- 21079594
TI  - Grand challenge commentary: Exploiting single-cell variation for new antibiotics.
AB  - Variations between single members of a bacterial population can lead to
      antibiotic resistance that is not gene based. The future of effective infectious
      disease management might depend on a better understanding of this phenomenon and
      the potential to manipulate both it and microbial population dynamics in general.

PMID- 21079595
TI  - Grand challenge commentary: Chassis cells for industrial biochemical production.
AB  - Hyper-performing whole-cell catalysts are required for the renewable and
      sustainable production of petrochemical replacements. Chassis cells-self
      replicating minimal machines that can be tailored for the production of specific
      chemicals-will provide the starting point for designing these hyper-performing
      'turbo cells'.

PMID- 21079596
TI  - Grand challenge commentary: Chemical transdifferentiation and regenerative
      medicine.
AB  - The ability to alter cell identity with small molecules represents a powerful
      approach to restore biological function lost because of cellular deficiency.
      Developing this capability through advances in chemical biology could have an
      enormous impact on human health.

PMID- 21079597
TI  - Chaperones: A story of thrift unfolds.

PMID- 21079598
TI  - Molecular probes: Getting lucky in the lysosome.

PMID- 21079599
TI  - Glycobiology: Cellulose squeezes through.

PMID- 21079600
TI  - Imaging: Visualizing a neuronal handshake.

PMID- 21079601
TI  - Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded
      proteins.
AB  - A hallmark of many neurodegenerative diseases is accumulation of misfolded
      proteins within neurons, leading to cellular dysfunction and cell death. Although
      several mechanisms have been proposed to link protein misfolding to cellular
      toxicity, the connection remains enigmatic. Here, we report a cell death pathway
      involving protein disulfide isomerase (PDI), a protein chaperone that catalyzes
      isomerization, reduction and oxidation of disulfides. Through a small molecule
      screening approach, we discovered five structurally distinct compounds that
      prevent apoptosis induced by mutant huntingtin protein. Using modified Huisgen
      cycloaddition chemistry, we then identified PDI as the molecular target of these
      small molecules. Expression of polyglutamine-expanded huntingtin exon 1 in PC12
      cells caused PDI to accumulate at mitochondrial-associated ER membranes and
      trigger apoptotic cell death via mitochondrial outer-membrane permeabilization.
      Inhibiting PDI in rat brain cells suppressed the toxicity of mutant huntingtin
      exon 1 and Abeta peptides processed from the amyloid precursor protein. This pro
      apoptotic function of PDI represents a new mechanism linking protein misfolding
      and apoptotic cell death.

PMID- 21079602
TI  - Ultrasensitive in situ visualization of active glucocerebrosidase molecules.
AB  - Deficiency of glucocerebrosidase (GBA) underlies Gaucher disease, a common
      lysosomal storage disorder. Carriership for Gaucher disease has recently been
      identified as major risk for parkinsonism. Presently, no method exists to
      visualize active GBA molecules in situ. We here report the design, synthesis and
      application of two fluorescent activity-based probes allowing highly specific
      labeling of active GBA molecules in vitro and in cultured cells and mice in vivo.
      Detection of in vitro labeled recombinant GBA on slab gels after electrophoresis
      is in the low attomolar range. Using cell or tissue lysates, we obtained
      exclusive labeling of GBA molecules. We present evidence from fluorescence
      activated cell sorting analysis, fluorescence microscopy and pulse-chase
      experiments of highly efficient labeling of GBA molecules in intact cells as well
      as tissues of mice. In addition, we illustrate the use of the fluorescent probes
      to study inhibitors and tentative chaperones in living cells.

PMID- 21079604
TI  - Touch gives new life: mechanosensation modulates spinal cord adult neurogenesis.
AB  - The ability to respond to a wide range of novel touch sensations and to habituate
      upon repeated exposures is fundamental for effective sensation. In this study we
      identified adult spinal cord neurogenesis as a potential novel player in the
      mechanism of tactile sensation. We demonstrate that a single exposure to a novel
      mechanosensory stimulus induced immediate proliferation of progenitor cells in
      the spinal dorsal horn, whereas repeated exposures to the same stimulus induced
      neuronal differentiation and survival. Most of the newly formed neurons
      differentiated toward a GABAergic fate. This touch-induced neurogenesis reflected
      the novelty of the stimuli, its diversity, as well as stimulus duration.
      Introducing adult neurogenesis as a potential mechanism of response to a novel
      stimulus and for habituation to repeated sensory exposures opens up potential new
      directions in treating hypersensitivity, pain and other mechanosensory disorders.

PMID- 21079605
TI  - Gene expression patterns in the hippocampus and amygdala of endogenous depression
      and chronic stress models.
AB  - The etiology of depression is still poorly understood, but two major causative
      hypotheses have been put forth: the monoamine deficiency and the stress
      hypotheses of depression. We evaluate these hypotheses using animal models of
      endogenous depression and chronic stress. The endogenously depressed rat and its
      control strain were developed by bidirectional selective breeding from the Wistar
      Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY
      More Immobile (WMI) substrain shows high immobility/despair-like behavior in the
      forced swim test (FST), while the control substrain, WKY Less Immobile (WLI),
      shows no depressive behavior in the FST. Chronic stress responses were
      investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and
      behaviorally distinct strains of rats. Animals were either not stressed (NS) or
      exposed to chronic restraint stress (CRS). Genome-wide microarray analyses
      identified differentially expressed genes in hippocampi and amygdalae of the
      endogenous depression and the chronic stress models. No significant difference
      was observed in the expression of monoaminergic transmission-related genes in
      either model. Furthermore, very few genes showed overlapping changes in the WMI
      vs WLI and CRS vs NS comparisons, strongly suggesting divergence between
      endogenous depressive behavior- and chronic stress-related molecular mechanisms.
      Taken together, these results posit that although chronic stress may induce
      depressive behavior, its molecular underpinnings differ from those of endogenous
      depression in animals and possibly in humans, suggesting the need for different
      treatments. The identification of novel endogenous depression-related and chronic
      stress response genes suggests that unexplored molecular mechanisms could be
      targeted for the development of novel therapeutic agents.

PMID- 21079606
TI  - Parental psychopathology and the risk of suicidal behavior in their offspring:
      results from the World Mental Health surveys.
AB  - Previous research suggests that parental psychopathology predicts suicidal
      behavior among offspring; however, the more fine-grained associations between
      specific parental disorders and distinct stages of the pathway to suicide are not
      well understood. We set out to test the hypothesis that parental disorders
      associated with negative mood would predict offspring suicide ideation, whereas
      disorders characterized by impulsive aggression (for example, antisocial
      personality) and anxiety/agitation (for example, panic disorder) would predict
      which offspring act on their suicide ideation and make a suicide attempt. Data
      were collected during face-to-face interviews conducted on nationally
      representative samples (N=55 299; age 18+) from 21 countries around the world. We
      tested the associations between a range of parental disorders and the onset and
      persistence over time (that is, time since most recent episode controlling for
      age of onset and time since onset) of subsequent suicidal behavior (suicide
      ideation, plans and attempts) among offspring. Analyses tested bivariate and
      multivariate associations between each parental disorder and distinct forms of
      suicidal behavior. Results revealed that each parental disorder examined
      increased the risk of suicide ideation among offspring, parental generalized
      anxiety and depression emerged as the only predictors of the onset and
      persistence (respectively) of suicide plans among offspring with ideation,
      whereas parental antisocial personality and anxiety disorders emerged as the only
      predictors of the onset and persistence of suicide attempts among ideators. A
      dose-response relation between parental disorders and respondent risk of suicide
      ideation and attempt was also found. Parental death by suicide was a particularly
      strong predictor of persistence of suicide attempts among offspring. These
      associations remained significant after controlling for comorbidity of parental
      disorders and for the presence of mental disorders among offspring. These
      findings should inform future explorations of the mechanisms of intergenerational
      transmission of suicidal behavior.

PMID- 21079607
TI  - A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa.
AB  - Anorexia nervosa (AN) is a mental illness with high mortality that most commonly
      afflicts adolescent female individuals. Clinical symptoms include chronic food
      refusal, weight loss and body image distortions. We carried out a genome-wide
      association study on 1033 AN cases and 3733 pediatric control subjects, all of
      whom were of European ancestry and were genotyped on the Illumina HumanHap610
      platform (Illumina, San Diego, CA, USA). We confirmed that common single
      nucleotide polymorphisms (SNPs) within OPRD1 (rs533123, P=0.0015) confer risk for
      AN, and obtained suggestive evidence that common SNPs near HTR1D (rs7532266,
      P=0.04) confer risk for restricting-type AN specifically. However, no SNPs
      reached genome-wide significance in our data, whereas top association signals
      were detected near ZNF804B, CSRP2BP, NTNG1, AKAP6 and CDH9. In parallel, we
      performed genome-wide analysis on copy number variations (CNVs) using the signal
      intensity data from the SNP arrays. We did not find evidence that AN cases have
      more CNVs than control subjects, nor do they have over-representation of rare or
      large CNVs. However, we identified several regions with rare CNVs that were only
      observed in AN cases, including a recurrent 13q12 deletion (1.5 Mb) disrupting
      SCAS in two cases, and CNVs disrupting the CNTN6/CNTN4 region in several AN
      cases. In conclusion, our study suggests that both common SNPs and rare CNVs may
      confer genetic risk to AN. These results point to intriguing genes that await
      further validation in independent cohorts for confirmatory roles in AN.

PMID- 21079610
TI  - Disrupted in Schizophrenia-1 regulates intracellular trafficking of mitochondria
      in neurons.

PMID- 21079609
TI  - Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt
      fetal survival and may perturb social behavior in adult mice.
AB  - Approximately 40-50% of individuals affected by tuberous sclerosis (TSC) develop
      autism spectrum disorders (ASDs). One possible explanation for this partial
      penetrance is an interaction between TSC gene mutations and other risk factors
      such as gestational immune activation. In this study, we report the interactive
      effects of these two ASD risk factors in a mouse model of TSC. Combined, but not
      single, exposure had adverse effects on intrauterine survival. Additionally,
      provisional results suggest that these factors synergize to disrupt social
      approach behavior in adult mice. Moreover, studies in human populations are
      consistent with an interaction between high seasonal flu activity in late
      gestation and TSC mutations in ASD. Taken together, our studies raise the
      possibility of a gene * environment interaction between heterozygous TSC gene
      mutations and gestational immune activation in the pathogenesis of TSC-related
      ASD.

PMID- 21079611
TI  - The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in
      adult patients with acute myeloid leukemia.
AB  - Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation
      in acute myeloid leukemia (AML) have been characterized, its prognostic
      significance remains controversial and its stability has not been investigated.
      We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1
      R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively.
      Compared with wild-type IDH2, mutation of IDH2 was associated with higher
      platelet counts, intermediate-risk or normal karyotype and isolated +8, but was
      inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was
      mutually exclusive with WT1 mutation and chromosomal translocations involving
      core-binding factors. All these correlations became stronger when IDH1 and IDH2
      mutations were considered together. Multivariate analysis revealed IDH2 mutation
      as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype
      conferred especially negative impact on survival. Compared with IDH2 R140
      mutation, IDH2 R172 mutation was associated with younger age, lower white blood
      cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1
      mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121
      patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation
      is a stable marker during disease evolution and confers favorable prognosis.

PMID- 21079612
TI  - Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization.
AB  - Under normal conditions, the great majority of hematopoietic stem/progenitors
      cells (HSPCs) reside in the bone marrow. The number of HSPCs in the circulation
      can be markedly increased in response to a number of stimuli, including
      hematopoietic growth factors, myeloablative agents and environmental stresses
      such as infection. The ability to 'mobilize' HSPCs from the bone marrow to the
      blood has been exploited clinically to obtain HSPCs for stem cell transplantation
      and, more recently, to stimulate therapeutic angiogenesis at sites of tissue
      ischemia. Moreover, there is recent interest in the use of mobilizing agents to
      sensitize leukemia and other hematopoietic malignancies to cytotoxic agents. Key
      to optimizing clinical mobilizing regimens is an understanding of the fundamental
      mechanisms of HSPC mobilization. In this review, we discuss recent advances in
      our understanding of the mechanisms by which granulocyte colony-stimulating
      factor (G-CSF), the prototypical mobilizing agent, induces HSPC mobilization.

PMID- 21079613
TI  - JAK inhibitor therapy for myelofibrosis: critical assessment of value and
      limitations.
AB  - The discovery of JAK2V617F has rejuvenated interest in Janus kinase (JAK)-signal
      transducer and activator of transcription (STAT), both as an oncogenic pathway
      and a drug target in BCR-ABL1-negative myeloproliferative neoplasms (MPN).
      However, the complexity of these diseases in terms of both clonal structure and
      mutation repertoire makes it unlikely that JAK inhibitor therapy will replicate
      what has been achieved with imatinib in chronic myeloid leukemia. Consistent with
      this view, JAK inhibitor therapy in myelofibrosis has not yet produced complete
      or partial remissions. However, most patients treated with a JAK2 (TG101348) or
      JAK1/2 (INCB018424) inhibitor experienced substantial improvement in
      constitutional symptoms and reduction in spleen size; the mechanism of action for
      INCB018424 includes anti-JAK1-mediated downregulation of proinflammatory
      cytokines. These observations complicate the choice of primary end points in
      clinical trials that would be robust enough to support regulatory approval.
      TG101348 and INCB018424 are the vanguard of JAK inhibitor therapy in
      myelofibrosis, but newer JAK inhibitors might have a broader spectrum of
      activity; preliminary results with CYT387 suggest responses in both anemia and
      splenomegaly. Outstanding issues regarding these drugs include identification of
      the optimal dosing strategy, their role (if any) in the treatment of polycythemia
      vera or essential thrombocythemia, and the potential for combining them with
      other therapeutic agents.

PMID- 21079608
TI  - The GABAergic deficit hypothesis of major depressive disorder.
AB  - Increasing evidence points to an association between major depressive disorders
      (MDDs) and diverse types of GABAergic deficits. In this review, we summarize
      clinical and preclinical evidence supporting a central and causal role of
      GABAergic deficits in the etiology of depressive disorders. Studies of depressed
      patients indicate that MDDs are accompanied by reduced brain concentration of the
      inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and by alterations in
      the subunit composition of the principal receptors (GABA(A) receptors) mediating
      GABAergic inhibition. In addition, there is abundant evidence that suggests that
      GABA has a prominent role in the brain control of stress, the most important
      vulnerability factor in mood disorders. Furthermore, preclinical evidence
      suggests that currently used antidepressant drugs (ADs) designed to alter
      monoaminergic transmission and nonpharmacological therapies may ultimately act to
      counteract GABAergic deficits. In particular, GABAergic transmission has an
      important role in the control of hippocampal neurogenesis and neural maturation,
      which are now established as cellular substrates of most if not all
      antidepressant therapies. Finally, comparatively modest deficits in GABAergic
      transmission in GABA(A) receptor-deficient mice are sufficient to cause
      behavioral, cognitive, neuroanatomical and neuroendocrine phenotypes, as well as
      AD response characteristics expected of an animal model of MDD. The GABAergic
      hypothesis of MDD suggests that alterations in GABAergic transmission represent
      fundamentally important aspects of the etiological sequelae of MDDs that are
      reversed by monoaminergic AD action.

PMID- 21079614
TI  - Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb.
AB  - Precise regulatory mechanisms are required to appropriately modulate the cellular
      levels of transcription factors controlling cell fate decisions during blood cell
      development. In this study, we show that miR-126 is a novel physiological
      regulator of the proto-oncogene c-myb during definitive hematopoiesis. We show
      that knockdown of miR-126 results in increased c-Myb levels and promotes
      erythropoiesis at the expense of thrombopoiesis in vivo. We further provide
      evidence that specification of thrombocyte versus erythrocyte cell lineages is
      altered by the concerted activities of the microRNAs (miRNAs) miR-126 and miR
      150. Both miRNAs are required but not sufficient individually to precisely
      regulate the cell fate decision between erythroid and megakaryocytic lineages
      during definitive hematopoiesis in vivo. These results support the notion that
      miRNAs not only function to provide precision to developmental programs but also
      are essential determinants in the control of variable potential functions of a
      single gene during hematopoiesis.

PMID- 21079617
TI  - No compelling evidence that sibutramine prolongs life in rodents despite
      providing a dose-dependent reduction in body weight.
AB  - OBJECTIVE: The health and longevity effects of body weight reduction resulting
      from exercise and caloric restriction in rodents are well known, but less is
      known about whether similar effects occur with weight reduction from the use of a
      pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake
      inhibitor. RESULTS AND CONCLUSION: Using data from a 2-year toxicology study of
      sibutramine in Sprague-Dawley CD rats and CD-1 mice, despite a dose-dependent
      reduction in food intake and body weight in rats compared with controls, and a
      body weight reduction in mice at the highest dose, there was no compelling
      evidence for reductions in mortality rate.

PMID- 21079615
TI  - Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review.
AB  - Bisphosphonate-associated osteonecrosis (BON) is a complication that almost
      exclusively affects the jaw bones. The clinical presentation of BON often mimics
      that of other conditions, such as routine dental disease, osteoradionecrosis or
      avascular necrosis; therefore, diagnosis can be difficult. As this complication
      has only been recognized within the past 10 years, management strategies for
      patients with BON are poorly defined. Physicians must choose between continuing
      the bisphosphonate therapy (to reduce the risk of skeletal complications in
      patients with metastatic bone disease or osteoporosis) and discontinuing the drug
      (to possibly improve the odds for tissue healing). A conservative or aggressive
      management strategy must be chosen with limited evidence that the outcome of
      either strategy will be successful. BON is most prevalent in patients with cancer
      using intravenous nitrogen-containing bisphosphonates. The pathobiology of this
      complication is not fully understood and the diagnosis relies on the clinical
      manifestations of the condition. Future research should focus on the
      pathobiological mechanisms involved in the development of BON, which could help
      explain why this complication affects only a small number of those who use
      bisphosphonates, and also suggest strategies for prevention and management.

PMID- 21079618
TI  - Obesity predicts persistence of pain in children with functional gastrointestinal
      disorders.
AB  - OBJECTIVE: The possible effect of obesity in the outcome of treated children with
      abdominal pain-related functional gastrointestinal disorders (FGIDs) has not yet
      been studied. We hypothesized that obesity is associated with a poor long-term
      prognosis in children with FGIDs. STUDY DESIGN: Prospective cohort study in an
      outpatient clinic-based sample of patients diagnosed with abdominal pain-related
      FGIDs. Principal outcome measured was persistence of pain at long-term follow-up
      (12-15 months). Frequency of pain, intensity of pain, school absenteeism and
      disruption of daily activities were compared between obese and non-obese
      subjects. RESULTS: The group mean age was 13.27+/-3.84 years, distribution of
      diagnosis was 32% (functional abdominal pain), 42.5% (irritable bowel syndrome)
      and 25.5% (functional dyspepsia). Overall, 20.2% of patients were obese. A total
      of 116 patients (61.7%) reported abdominal pain and 72 (38.3%) were asymptomatic
      at long-term follow-up. Obese patients were more likely to have abdominal pain
      (P<0.0001), higher intensity of pain (P=0.0002), higher frequency of pain
      (P=0.0032), school absenteeism (P<0.0001) and disruption of daily activities
      (P<0.0001) at follow-up than non-obese patients. CONCLUSION: Obesity is
      associated with poor outcome and disability at long-term follow-up in children
      with abdominal pain-related FGIDs. Our novel findings could have important
      implications in the prognosis and management of FGIDs.

PMID- 21079620
TI  - 'Traffic-light' nutrition labelling and 'junk-food' tax: a modelled comparison of
      cost-effectiveness for obesity prevention.
AB  - INTRODUCTION: Cost-effectiveness analyses are important tools in efforts to
      prioritise interventions for obesity prevention. Modelling facilitates evaluation
      of multiple scenarios with varying assumptions. This study compares the cost
      effectiveness of conservative scenarios for two commonly proposed policy-based
      interventions: front-of-pack 'traffic-light' nutrition labelling (traffic-light
      labelling) and a tax on unhealthy foods ('junk-food' tax). METHODS: For traffic
      light labelling, estimates of changes in energy intake were based on an assumed
      10% shift in consumption towards healthier options in four food categories
      (breakfast cereals, pastries, sausages and preprepared meals) in 10% of adults.
      For the 'junk-food' tax, price elasticities were used to estimate a change in
      energy intake in response to a 10% price increase in seven food categories
      (including soft drinks, confectionery and snack foods). Changes in population
      weight and body mass index by sex were then estimated based on these changes in
      population energy intake, along with subsequent impacts on disability-adjusted
      life years (DALYs). Associated resource use was measured and costed using pathway
      analysis, based on a health sector perspective (with some industry costs
      included). Costs and health outcomes were discounted at 3%. The cost
      effectiveness of each intervention was modelled for the 2003 Australian adult
      population. RESULTS: Both interventions resulted in reduced mean weight (traffic
      light labelling: 1.3 kg (95% uncertainty interval (UI): 1.2; 1.4); 'junk-food'
      tax: 1.6 kg (95% UI: 1.5; 1.7)); and DALYs averted (traffic-light labelling:
      45,100 (95% UI: 37,700; 60,100); 'junk-food' tax: 559,000 (95% UI: 459,500;
      676,000)). Cost outlays were AUD81 million (95% UI: 44.7; 108.0) for traffic
      light labelling and AUD18 million (95% UI: 14.4; 21.6) for 'junk-food' tax. Cost
      effectiveness analysis showed both interventions were 'dominant' (effective and
      cost-saving). CONCLUSION: Policy-based population-wide interventions such as
      traffic-light nutrition labelling and taxes on unhealthy foods are likely to
      offer excellent 'value for money' as obesity prevention measures.

PMID- 21079616
TI  - Lipodystrophy: pathophysiology and advances in treatment.
AB  - Lipodystrophy is a medical condition characterized by complete or partial loss of
      adipose tissue. Not infrequently, lipodystrophy occurs in combination with
      pathological accumulation of adipose tissue at distinct anatomical sites.
      Patients with lipodystrophy exhibit numerous metabolic complications, which
      indicate the importance of adipose tissue as an active endocrine organ. Not only
      the total amount but also the appropriate distribution of adipose tissue depots
      contribute to the metabolic state. Genetic and molecular research has improved
      our understanding of the mechanisms underlying lipodystrophy. Circulating levels
      of hormones secreted by the adipose tissue, such as leptin and adiponectin, are
      greatly reduced in distinct subpopulations of patients with lipodystrophy. This
      finding rationalizes the use of these adipokines or of agents that increase their
      circulating levels, such as peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists, for therapeutic purposes. Other novel therapeutic
      approaches, including the use of growth hormone and growth-hormone-releasing
      factors, are also being studied as potential additions to the therapeutic
      armamentarium. New insights gained from research and clinical trials could
      potentially revolutionize the management of this difficult-to-treat condition.

PMID- 21079621
TI  - Anatomical study of blood supply to the spinal cord in the rabbit.
AB  - STUDY DESIGN: The study was carried out in rabbit. OBJECTIVE: To investigate the
      arterial blood supply of the spinal cord in rabbit as model in experimental
      spinal cord ischemia surgery. SETTING: The study was carried out in the
      Department of Anatomy, Histology and Physiology, University of Veterinary
      Medicine and Pharmacy in Kosice, Slovak Republic. METHODS: The study was carried
      out on 10 adult New Zealand white rabbits. We prepared corrosion casts of
      arterial system of spinal cord. Batson's corrosion casting kit no. 17 was used as
      a casting medium. RESULTS: The presence of branches entering arteria spinalis
      ventralis in the thoracic region was observed in 71% of the cases on the left
      side and in 29% on the right side. In the lumbar region, left-sided branches were
      observed in 52% of the cases and right-sided in 48% of the cases. The artery of
      Adamkiewicz was present in 50% of the cases as left-sided and in 50% as right
      sided. CONCLUSION: Documenting the anatomical variations in spinal cord blood
      supply in the rabbit will aid in the planning of future experimental studies and
      determining the clinical relevance on such studies.

PMID- 21079619
TI  - Obesity impairs skeletal muscle AMPK signaling during exercise: role of
      AMPKalpha2 in the regulation of exercise capacity in vivo.
AB  - OBJECTIVE: Skeletal muscle AMP-activated protein kinase (AMPK)alpha2 activity is
      impaired in obese, insulin-resistant individuals during exercise. We determined
      whether this defect contributes to the metabolic dysregulation and reduced
      exercise capacity observed in the obese state. DESIGN: C57BL/6J wild-type (WT)
      mice and/or mice expressing a kinase dead AMPKalpha2 subunit in skeletal muscle
      (alpha2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15
      weeks, mice performed an exercise stress test to determine exercise capacity. In
      WT mice, muscle glucose uptake and skeletal muscle AMPKalpha2 activity was
      assessed in chronically catheterized mice (carotid artery/jugular vein) at 16
      weeks. In a separate study, HF-fed WT and alpha2-KD mice performed 5 weeks of
      exercise training (from 15 to 20 weeks of age) to test whether AMPKalpha2 is
      necessary to restore work tolerance. RESULTS: HF-fed WT mice had reduced exercise
      tolerance during an exercise stress test, and an attenuation in muscle glucose
      uptake and AMPKalpha2 activity during a single bout of exercise (P<0.05 versus
      chow). In chow-fed alpha2-KD mice, running speed and time were impaired ~45 and
      ~55%, respectively (P<0.05 versus WT chow); HF feeding further reduced running
      time ~25% (P<0.05 versus alpha2-KD chow). In response to 5 weeks of exercise
      training, HF-fed WT and alpha2-KD mice increased maximum running speed ~35%
      (P<0.05 versus pre-training) and maintained body weight at pre-training levels,
      whereas body weight increased in untrained HF WT and alpha2-KD mice. Exercise
      training restored running speed to levels seen in healthy, chow-fed mice.
      CONCLUSION: HF feeding impairs AMPKalpha2 activity in skeletal muscle during
      exercise in vivo. Although this defect directly contributes to reduced exercise
      capacity, findings in HF-fed alpha2-KD mice show that AMPKalpha2-independent
      mechanisms are also involved. Importantly, alpha2-KD mice on a HF-fed diet adapt
      to regular exercise by increasing exercise tolerance, demonstrating that this
      adaptation is independent of skeletal muscle AMPKalpha2 activity.

PMID- 21079622
TI  - Neurophysiological characterization of motor recovery in acute spinal cord
      injury.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: This study was designed to
      neurophysiologically characterize motor control recovery after spinal cord injury
      (SCI). SETTING: University of Louisville, Louisville, Kentucky, USA. MATERIAL:
      Eleven acute SCI admissions and five non-injured subjects were recruited for this
      study. METHODS: The American Spinal Injury Association Impairment Scale (AIS) was
      used to categorize injury level and severity at onset. Multimuscle surface
      electromyography (sEMG) recording protocol of reflex and volitional motor tasks
      was initially performed between the day of injury and 11 days post onset (6.4+/
      3.6, mean+/-s.d. days). Follow-up data were recorded for up to 17 months after
      injury. Initial AIS distribution was as follows: 4 AIS-A; 2 AIS-C; 5 AIS-D.
      Multimuscle activation patterns were quantified from the sEMG amplitudes of
      selected muscles using a vector-based calculation that produces separate values
      for the magnitude and similarity of SCI test-subject patterns to those of non
      injured subjects for each task. RESULTS: In SCI subjects, overall sEMG amplitudes
      were lower after SCI. Prime mover muscle voluntary recruitment was slower and
      multimuscle patterns were disrupted by SCI. Recovery occurred in 9 of the 11
      subjects, showing an increase in sEMG amplitudes, more rapid prime mover muscle
      recruitment rates and the progressive normalization of the multimuscle activation
      patterns. The rate of increase was highly individualized, differing over time by
      limb and proximal or distal joint within each subject and across the SCI group.
      CONCLUSIONS: Recovery of voluntary motor function can be quantitatively tracked
      using neurophysiological methods in the domains of time and multimuscle motor
      unit activation.

PMID- 21079623
TI  - Posterior/anterior combined surgery for thoracolumbar burst fractures--posterior
      instrumentation with pedicle screws and laminar hooks, anterior decompression and
      strut grafting.
AB  - STUDY DESIGN: A prospective clinical study. OBJECTIVE: The purpose of this study
      was to evaluate prospectively a large group of patients with thoracolumbar burst
      fractures who were treated with a posterior/anterior combined procedure and to
      report on the surgical outcomes, complications and radiographic results. METHODS:
      A total of 100 consecutive patients were surgically managed with posterior
      instrumentation, anterior decompression and anterior strut grafting. There were
      71 males and 29 females; the mean age was 36 years. Patients with osteoporotic
      delayed vertebral body collapse were excluded. The mean follow-up period was 30
      months. Surgical outcomes such as operative time, blood loss and sagittal
      alignment were investigated. A neurological assessment was performed by a rating
      system based on the American Spine Injury Association impairment scale. An
      interbody fusion was judged using plain X-ray and computed tomographic scans.
      RESULTS: The mean operative time was 256 min and the mean operative bleeding was
      985 ml. Most of the patients were ambulatory within 3 days after surgery. Of the
      76 patients with neurological injury, 54 (71.1%) recovered function following
      surgery. The mean local kyphosis angle was 12.2 degrees  kyphotic preoperatively
      and 0.8 degrees  lordotic at the final observation. The mean correction angle was
      15.7 degrees  and correction loss was 2.6 degrees . No instrumentation failure
      was observed and the postoperative fusion rate was 99%. CONCLUSIONS:
      Posterior/anterior combined surgery with posterior pedicle screws and hooks
      fixation, and reconstruction by simultaneous strut grafting and anterior
      decompression, achieved short segment fixation and can be a useful option for
      surgically treating thoracolumbar burst fractures.

PMID- 21079625
TI  - Support for peer review.

PMID- 21079624
TI  - Supernumerary phantom limbs in spinal cord injury.
AB  - STUDY DESIGN AND OBJECTIVES: Case report and review of supernumerary phantom
      limbs in patients suffering from spinal cord injury (SCI). SETTING: SCI
      rehabilitation centre. CASE REPORT: After a ski accident, a 71-year-old man
      suffered an incomplete SCI (level C3; AIS C, central cord syndrome), with a C3/C4
      dislocation fracture. From the first week after injury, he experienced a phantom
      duplication of both upper limbs that lasted for 7 months. The supernumerary limbs
      were only occasionally related to painful sensation, specifically when they were
      perceived as crossed on his trunk. Although the painful sensations were
      responsive to pain medication, the presence of the illusory limb sensations were
      persistent. During neurological recovery, the supernumerary limbs gradually
      disappeared. A rubber hand illusion paradigm was used twice during recovery to
      monitor the patient's ability to integrate visual, tactile and proprioceptive
      stimuli. CONCLUSION: Overall, the clinical relevance of supernumerary phantom
      limbs is not clear, specific treatment protocols have not yet been developed, and
      the underlying neural mechanisms are not fully understood. Supernumerary phantom
      limbs have been previously reported in patients with (sub)cortical lesions, but
      might be rather undocumented in patients suffering from traumatic SCI. For the
      appropriate diagnosis and treatment after SCI, supernumerary phantoms should be
      distinguished from other phantom sensations and pain syndromes after SCI.

PMID- 21079626
TI  - Multistoried roles for B lymphocytes in autoimmunity.
AB  - In autoimmune disease, multifaceted approaches are being explored to tailor a
      particular treatment that targets a specific cell at the appropriate disease
      stage. The key roles of B lymphocytes have enabled them to enter the clinical
      arena. In turn, clinical trials have suggested several leads for future research.

PMID- 21079627
TI  - Ten years of the Global Alliance for Vaccines and Immunization: challenges and
      progress.
AB  - Diseases preventable by underused vaccines cause the death of approximately 3
      million children per year. The Global Alliance for Vaccines and Immunization
      (GAVI) was launched 10 years ago to tackle this appalling situation.

PMID- 21079628
TI  - Lymphocytes, Jim Gowans and in vivo veritas.

PMID- 21079629
TI  - Regulatory ripples.
AB  - Regulatory T cells come in many different forms depending on their mode of action
      or developmental origin. Data now show that interleukin 35, an immunomodulatory
      cytokine secreted by regulatory T cells, and interleukin 10 induce so-called
      'iTR35 cells', which may have an important role in the phenomenon of infectious
      tolerance.

PMID- 21079630
TI  - Skin function for human CD1a-reactive T cells.
AB  - Human CD4+ T cells that produce interleukin 22 are an essential component of skin
      defense and repair. New evidence shows that these T cells recognize CD1a-lipid
      complexes on Langerhans cells.

PMID- 21079631
TI  - More things in heaven and earth: defining innate and adaptive immunity.
AB  - Natural killer cells have emerged as key components of innate immunity with
      critical antimicrobial functions. New work showing that they can also be accessed
      by vaccination to deliver antigen-specific memory responses and protect against
      subsequent viral infections challenges the traditional distinctions made between
      innate and adaptive immunity.

PMID- 21079633
TI  - Cellular mechanisms that control mistranslation.
AB  - Mistranslation broadly encompasses the introduction of errors during any step of
      protein synthesis, leading to the incorporation of an amino acid that is
      different from the one encoded by the gene. Recent research has vastly enhanced
      our understanding of the mechanisms that control mistranslation at the molecular
      level and has led to the discovery that the rates of mistranslation in vivo are
      not fixed but instead are variable. In this Review we describe the different
      steps in translation quality control and their variations under different growth
      conditions and between species though a comparison of in vitro and in vivo
      findings. This provides new insights as to why mistranslation can have both
      positive and negative effects on growth and viability.

PMID- 21079634
TI  - RNAs: regulators of bacterial virulence.
AB  - RNA-based pathways that regulate protein expression are much more widespread than
      previously thought. Regulatory RNAs, including 5' and 3' untranslated regions
      next to the coding sequence, cis-acting antisense RNAs and trans-acting small non
      coding RNAs, are effective regulatory molecules that can influence protein
      expression and function in response to external cues such as temperature, pH and
      levels of metabolites. This Review discusses the mechanisms by which these
      regulatory RNAs, together with accessory proteins such as RNases, control the
      fate of mRNAs and proteins and how this regulation influences virulence in
      pathogenic bacteria.

PMID- 21079635
TI  - New insights into the formation of fungal aromatic polyketides.
AB  - Fungal aromatic polyketides constitute a large family of bioactive natural
      products and are synthesized by the non-reducing group of iterative polyketide
      synthases (PKSs). Their diverse structures arise from selective enzymatic
      modifications of reactive, enzyme-bound poly-beta-keto intermediates. How
      iterative PKSs control starter unit selection, polyketide chain initiation and
      elongation, intermediate folding and cyclization, selective redox or modification
      reactions during assembly, and product release are central mechanistic questions
      underlying iterative catalysis. This Review highlights recent insights into these
      questions, with a particular focus on the biosynthetic programming of fungal
      aromatic polyketides, and draws comparisons with the allied biosynthetic
      processes in bacteria.

PMID- 21079636
TI  - Paroxysmal extreme pain disorder: a molecular lesion of peripheral neurons.
AB  - BACKGROUND: a 3-month-old male infant presented, beginning on the second day of
      life, with paroxysmal painful events that started with tonic contraction of the
      whole body followed by erythematous harlequin-type color changes. INVESTIGATIONS:
      screening of the SCN9A gene, which encodes the voltage-gated sodium channel
      Na(V)1.7, identified a new mutation, Gly1607Arg, located within the domain IV S4
      voltage sensor. Whole-cell patch-clamp analysis demonstrated functional effects
      of the mutant channel that included impaired inactivation-a hallmark of
      paroxysmal extreme pain disorder (PEPD). DIAGNOSIS: the patient was diagnosed as
      having PEPD, an autosomal dominant disorder characterized by severe rectal pain
      triggered by defecation or perineal stimulation, usually followed by ocular or
      submaxillary pain. Erythematous flushing, sometimes in a harlequin pattern, can
      be a prominent feature of this condition. MANAGEMENT: treatment with
      carbamazepine (10 mg/kg/day) for approximately 3 months was ineffective in this
      case, and the parents made a decision to discontinue the drug. The mother was
      instructed to avoid painful stimuli that could trigger an episode.

PMID- 21079637
TI  - Blood pressure lowering in patients with diabetes--one level might not fit all.
AB  - Hypertension and diabetes mellitus frequently occur together, leading to
      increased complications and mortality in patients with both these conditions.
      Blood pressure (BP) goals for patients with diabetes have consistently been more
      aggressive than for patients without diabetes. Although the benefits of lowering
      BP are well documented, data to support this more aggressive goal are lacking. In
      fact, lowering BP might not always be better. We review the available evidence
      regarding BP treatment in patients with hypertension and diabetes from randomized
      clinical trials, as well as available observational data. We also consider
      evidence related to the J-shaped curve, which reflects the relationship between
      BP and outcomes in patients with diabetes, and make recommendations for treatment
      of BP on the basis of a patient's individual risk, as opposed to on the basis of
      aggressive BP targets recommended by global guidelines. In the future, a
      personalized approach will maximize the benefits from treatment.

PMID- 21079639
TI  - Mechanisms of vascular damage in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea
      cycles during sleep, which are associated with oxygen desaturation and sleep
      disruption. Up to 30% of the adult population in Western countries are thought to
      be affected by asymptomatic OSA and approximately 2-4% by symptomatic OSA (also
      known as obstructive sleep apnea syndrome, or OSAS). Controlled trials have
      demonstrated that OSAS causes hypertension and prospective epidemiological
      studies have indicated that OSAS might be an independent risk factor for stroke
      and myocardial ischemia. Three biological mechanisms are thought to underpin the
      association of OSA with endothelial dysfunction and arterial disease:
      intermittent hypoxia leading to increased oxidative stress, systemic
      inflammation, and sympathetic activity; intrathoracic pressure changes leading to
      excessive mechanical stress on the heart and large artery walls; and arousal
      induced reflex sympathetic activation with resultant repetitive blood-pressure
      rises. More clinical interventional trials are needed to determine the magnitude
      of the effect OSA has on cardiovascular damage and to enable a comparison with
      conventional vascular risk factors.

PMID- 21079641
TI  - Shaping the T-cell repertoire in the periphery.
AB  - Selection of T cells does not end with events in the thymus, but continues in
      extrathymic tissues and for the life of the organism. In this review, we examine
      how self-reactive T cells are rendered harmless and the processes that select for
      T cells that are most efficient at combating pathogens. The implications of
      peripheral T-cell selection for the immune response as animals age are discussed
      as is the critical role of dendritic cells in directing T-cell differentiation.

PMID- 21079640
TI  - Device therapy: Who may and who may not benefit from an ICD?

PMID- 21079638
TI  - Pathophysiology and epidemiology of abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAAs) are found in up to 8% of men aged >65 years,
      yet usually remain asymptomatic until they rupture. Rupture of an AAA and its
      associated catastrophic physiological insult carries overall mortality in excess
      of 80%, and 2% of all deaths are AAA-related. Pathologically, AAAs are associated
      with inflammation, smooth muscle cell apoptosis, and matrix degradation. Once
      thought to be a consequence of advanced atherosclerosis, accruing evidence
      indicates that AAAs are a focal representation of a systemic disease of the
      vasculature. Risk factors for AAAs include increasing age, male sex, smoking, and
      low HDL-cholesterol levels. Familial associations exist and although
      susceptibility genes have been described on the basis of candidate-gene studies,
      robust genetic studies have failed to discover causative gene mutations. The
      surgical management of AAAs has been revolutionized by minimally invasive
      endovascular repair. Ongoing randomized trials will establish whether
      endovascular repair confers a survival advantage over open surgery for patients
      with a ruptured AAA. In many countries, centralization of vascular surgical
      services has largely been driven by the improved outcomes of elective aneurysm
      surgery in specialized centers, the widespread adoption of endovascular
      techniques, and the introduction of screening programs.

PMID- 21079642
TI  - Induction of antigen-specific effector-phase tolerance following vaccination
      against a previously ignored B-cell lymphoma.
AB  - The mechanisms of immune evasion during haematological malignancies are poorly
      understood. As lymphomas grow in lymphoid organs, it would be expected that if
      these lymphomas express neo-antigens they should be readily detected by the
      immune system. To test this assumption, we generated a new non-Hodgkin B-cell
      lymphoma model expressing the model tumour neo-antigen Ovalbumin (OVA), and
      analysed the endogenous antigen-specific CD8(+) T-cell response that it elicited
      in recipient mice. The OVA+ lymphoma cells were eliminated by cytotoxic T
      lymphocytes (CTL) in mice that had been previously vaccinated against OVA. In
      contrast, the immune system of naive mice ignored the malignant cells even though
      these continuously expressed and presented OVA on their MHC class I molecules.
      This state of ignorance could be overcome by therapeutic vaccination, which led
      to the expansion of endogenous anti-OVA-specific CD8(+) T cells. However, the
      cytotoxic and interferon-gamma secretion capacity of these T cells were impaired.
      The tumour model that we describe thus reproduces several key aspects of human
      lymphoma; tumor ignorance can be broken by vaccination but the ensuing immune
      response remains ineffective. This model can be exploited to further understand
      the mechanisms of lymphoma immunoevasion and devise effective immunotherapy.

PMID- 21079643
TI  - The role of Aire in clonal selection.
AB  - In his clonal selection theory, Frank Macfarlane Burnet predicted that
      autoreactive lymphocytes are deleted to prevent autoimmunity. This and other
      principles of lymphocyte behavior outlined by Burnet guided many studies that
      lead to our current understanding of thymic selection. Thus, when the genetic
      mutation responsible for autoimmune polyglandular syndrome type 1 was mapped to
      the autoimmune regulator (AIRE) gene, and Aire was found to be highly expressed
      in thymic epithelium, studying the role of Aire in negative selection made sense
      in the context of modern models of thymic selection. We now know Aire is a
      transcription factor required for the expression of many tissue-specific antigens
      (TSAs) in the thymus. In the absence of functional Aire, human patients and mice
      develop multi-organ autoimmune disease because of a defect in thymic negative
      selection. In addition to its role in the thymus, recent work in our lab suggests
      that extrathymic Aire-expressing cells have an important role in the clonal
      deletion of autoreactive CD8+ T cells. In this review, we summarize the latest
      studies on thymic and peripheral Aire-expressing cells, as well as other TSA
      expressing stromal cell populations in peripheral lymphoid organs. We also
      discuss theoretical differences in thymic and peripheral Aire function that
      warrant further studies.

PMID- 21079644
TI  - Pharmacologic therapy for osteoarthritis--the era of disease modification.
AB  - Osteoarthritis (OA) is a prevalent and disabling condition for which few safe and
      effective therapeutic options are available. Current approaches are largely
      palliative and in an effort to mitigate the rising tide of increasing OA
      prevalence and disease impact, modifying the structural progression of OA has
      become a focus of drug development. This Review describes disease modification
      and discusses some of the challenges involved in the discovery and development of
      disease-modifying OA drugs (DMOADs). A variety of targeted agents are in mature
      phases of development; specific agents that are beyond preclinical development in
      phase II and III trials and show promise as potential DMOADs are discussed. A
      research agenda with respect to disease modification in OA is also provided, and
      some of the future challenges we face in this field are discussed.

PMID- 21079645
TI  - Genetic epidemiology of hip and knee osteoarthritis.
AB  - Osteoarthritis (OA) is the most common cause of arthritis and represents an
      enormous healthcare burden in industrialized societies. Current therapeutic
      approaches for OA are limited and are insufficient to prevent the initiation and
      progression of the disease. Genetic studies of patients with OA can help to
      unravel the molecular mechanisms responsible for specific disease manifestations,
      including joint damage, nociception and chronic pain. Indeed, these studies have
      identified molecules, such as growth/differentiation factor 5, involved in
      signaling cascades that are important for the pathology of joint components.
      Genome-wide association studies have uncovered a likely role in OA for the genes
      encoding structural extracellular matrix components (such as DVWA) and molecules
      involved in prostaglandin metabolism (such as DQB1 and BTNL2). A ~300 kilobase
      region in chromosome 7q22 is also associated with OA susceptibility. Finally, the
      identification of individuals at a high risk of OA and of total joint
      arthroplasty failure might be facilitated by the use of combinations of genetic
      markers, allowing for the application of preventive and disease-management
      strategies.

PMID- 21079646
TI  - Antipsychotic-induced vacuous chewing movements and extrapyramidal side effects
      are highly heritable in mice.
AB  - Pharmacogenomics is yet to fulfill its promise of manifestly altering clinical
      medicine. As one example, a predictive test for tardive dyskinesia (TD) (an
      adverse drug reaction consequent to antipsychotic exposure) could greatly improve
      the clinical treatment of schizophrenia but human studies are equivocal. A
      complementary approach is the mouse-then-human design in which a valid mouse
      model is used to identify susceptibility loci, which are subsequently tested in
      human samples. We used inbred mouse strains from the Mouse Phenome Project to
      estimate the heritability of haloperidol-induced activity and orofacial
      phenotypes. In all, 159 mice from 27 inbred strains were chronically treated with
      haloperidol (3 mg kg(-1) per day via subdermal slow-release pellets) and
      monitored for the development of vacuous chewing movements (VCMs; the mouse
      analog of TD) and other movement phenotypes derived from open-field activity and
      the inclined screen test. The test battery was assessed at 0, 30, 60, 90 and 120
      days in relation to haloperidol exposure. As expected, haloperidol caused marked
      changes in VCMs, activity in the open field and extrapyramidal symptoms (EPS).
      Unexpectedly, factor analysis demonstrated that these measures were imprecise
      assessments of a latent construct rather than discrete constructs. The
      heritability of a composite phenotype was ~0.9 after incorporation of the
      longitudinal nature of the design. Murine VCMs are a face valid animal model of
      antipsychotic-induced TD, and heritability estimates from this study support the
      feasibility of mapping of susceptibility loci for VCMs.

PMID- 21079647
TI  - Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse
      embryonic stem cells.
AB  - Although Activin/Nodal signaling regulates pluripotency of human embryonic stem
      (ES) cells, how this signaling acts in mouse ES cells remains largely unclear. To
      investigate this, we confirmed that mouse ES cells possess active Smad2-mediated
      Activin/Nodal signaling and found that Smad2-mediated Activin/Nodal signaling is
      dispensable for self-renewal maintenance but is required for proper
      differentiation toward the mesendoderm lineage. To gain insights into the
      underlying mechanisms, Smad2-associated genes were identified by genome-wide
      chromatin immunoprecipitation-chip analysis. The results showed that there is a
      transcriptional correlation between Smad2 binding and Activin/Nodal signaling
      modulation, and that the development-related genes were enriched among the Smad2
      bound targets. We further identified Tapbp as a key player in mesendoderm
      differentiation of mouse ES cells acting downstream of the Activin/Nodal-Smad2
      pathway. Taken together, our findings suggest that Smad2-mediated Activin/Nodal
      signaling orchestrates mesendoderm lineage commitment of mouse ES cells through
      direct modulation of corresponding developmental regulator expression.

PMID- 21079648
TI  - TET1 is a DNA-binding protein that modulates DNA methylation and gene
      transcription via hydroxylation of 5-methylcytosine.

PMID- 21079649
TI  - IDH1 mutant structures reveal a mechanism of dominant inhibition.

PMID- 21079650
TI  - Histone methyltransferase G9a contributes to H3K27 methylation in vivo.

PMID- 21079652
TI  - A switch from hBrm to Brg1 at IFNgamma-activated sequences mediates the
      activation of human genes.
AB  - The SWI/SNF chromatin-remodeling complexes utilize energy from ATP hydrolysis to
      reposition nucleosomes and regulate the expression of human genes. Here, we
      studied the roles of human Brahma (hBrm) and Brahma-related gene 1 (Brg1), the
      ATPase subunits of the SWI/SNF complexes, in regulating human genes. Our results
      indicate that both hBrm and Brg1 interact with Signal transducer and activator of
      transcription (Stat) 1 in vitro. However, Stat1 in its native form only recruits
      hBrm to IFNgamma-activated sequences (GAS) of individual genes; by contrast, in a
      stress-induced phosphorylated form, Stat1 mainly binds to Brg1. Under basal
      conditions, hBrm is recruited by native Stat1 to the GAS and exists in a
      mSin3/HDAC co-repressor complex on the hsp90alpha gene, which shows a compact
      chromatin structure. Upon heat-shock, hBrm is acetylated by p300 and dissociates
      from the co-repressor complex, which the phosphorylated Stat1 is increased, and
      binds and recruits Brg1 to the GAS, leading to elevated induction of the gene.
      This hBrm/Brg1 switch also occurs at the GAS of all of the three examined immune
      genes in heat-shocked cells; however, this switch only occurs in specific cell
      types upon exposure to IFNgamma. Regardless of the stimulus, the hBrm/Brg1 switch
      at the GAS elicits an increase in gene activity. Our data are consistent with the
      hypothesis that the hBrm/Brg1 switch is an indicator of the responsiveness of a
      gene to heat-shock or IFNgamma stimulation and may represent an "on-off switch"
      of gene expression in vivo.

PMID- 21079651
TI  - Role of NF-kappaB in the skeleton.
AB  - Since the discovery that deletion of the NF-kappaB subunits p50 and p52 causes
      osteopetrosis in mice, there has been considerable interest in the role of NF
      kappaB signaling in bone. NF-kappaB controls the differentiation or activity of
      the major skeletal cell types - osteoclasts, osteoblasts, osteocytes and
      chondrocytes. However, with five NF-kappaB subunits and two distinct activation
      pathways, not all NF-kappaB signals lead to the same physiologic responses. In
      this review, we will describe the roles of various NF-kappaB proteins in basal
      bone homeostasis and disease states, and explore how NF-kappaB inhibition might
      be utilized therapeutically.

PMID- 21079653
TI  - p53-mediated transcriptional regulation and activation of the actin cytoskeleton
      regulatory RhoC to LIMK2 signaling pathway promotes cell survival.
AB  - The central arbiter of cell fate in response to DNA damage is p53, which
      regulates the expression of genes involved in cell cycle arrest, survival and
      apoptosis. Although many responses initiated by DNA damage have been
      characterized, the role of actin cytoskeleton regulators is largely unknown. We
      now show that RhoC and LIM kinase 2 (LIMK2) are direct p53 target genes induced
      by genotoxic agents. Although RhoC and LIMK2 have well-established roles in actin
      cytoskeleton regulation, our results indicate that activation of LIMK2 also has a
      pro-survival function following DNA damage. LIMK inhibition by siRNA-mediated
      knockdown or selective pharmacological blockade sensitized cells to radio- or
      chemotherapy, such that treatments that were sub-lethal when administered singly
      resulted in cell death when combined with LIMK inhibition. Our findings suggest
      that combining LIMK inhibitors with genotoxic therapies could be more efficacious
      than single-agent administration, and highlight a novel connection between actin
      cytoskeleton regulators and DNA damage-induced cell survival mechanisms.

PMID- 21079654
TI  - Epidemiology of hypertensive kidney disease.
AB  - The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal
      disease (ESRD) attributable to hypertension continues to rise worldwide.
      Identifying the precise prevalence of CKD attributable to hypertension is
      difficult owing to the absence of uniform criteria to establish a diagnosis of
      hypertensive nephropathy. Despite the increasing prevalence of CKD-associated
      hypertension, awareness of hypertension among individuals with CKD remains
      suboptimal and rates of blood-pressure control remain poor. Targeted subgroups
      involved in studies of CKD seem to reach better rates of blood-pressure control,
      suggesting that this therapeutic goal can be achieved in patients with CKD.
      Elevated blood-pressure levels are associated with CKD progression. However, the
      optimal blood-pressure level and pharmacological agent remains unclear.
      Physicians treating patients with CKD must recognize the importance of
      maintaining optimal salt and volume balance to achieve blood-pressure goals.
      Furthermore, agents that modify the renin-angiotensin-aldosterone axis can be an
      important adjunct to therapy and physicians must monitor expected changes in
      serum creatinine and electrolyte levels after their administration. Hypertension
      remains a common factor complicating CKD. Future investigations identifying early
      signs of hypertension-related CKD, increasing awareness of the effects of
      hypertension in CKD and determining optimal therapeutic interventions might help
      reduce the incidence of hypertensive nephropathy.

PMID- 21079656
TI  - Radiosensitivity and repair kinetics of gamma-irradiated leukocytes from sporadic
      prostate cancer patients and healthy individuals assessed by alkaline comet
      assay.
AB  - BACKGROUND: Impaired DNA repair mechanism is one of the main causes of tumor
      genesis. Study of intrinsic radiosensitivity of cancer patients in a non-target
      tissue (e.g. peripheral blood) might show the extent of DNA repair deficiency of
      cells in affected individuals and might be used a predictor of cancer
      predisposition. METHODS: Initial radiation-induced DNA damage (ratio of Tail
      DNA/Head DNA), dose-response curves and kinetics of DNA repair in leukocytes from
      healthy volunteers and prostate cancer patients were assessed using alkaline
      comet assay after exposure to 60Co gamma rays. RESULTS: Results showed that
      higher levels of baseline and gamma rays induced DNA damage in leukocytes of
      prostate cancer cases than in controls. A similar dose response was obtained for
      both groups. After a repair time of 24 h following in vitro irradiation, samples
      from the healthy individuals showed no residual DNA damage in their leukocytes,
      whereas prostate cancer patients revealed more than 20 percent. Although similar
      initial radiosensitivity was observed for both groups, the repair kinetics of
      radiation induced DNA damage of leukocytes from prostate cancer cases and healthy
      subjects were statistically different. CONCLUSION: These results support the
      hypothesis that men affected by prostate cancer may have a constitutional genomic
      instability.

PMID- 21079655
TI  - Dengue: a continuing global threat.
AB  - Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral
      diseases. Each year, there are ~50 million dengue infections and ~500,000
      individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast
      Asia, the Pacific and the Americas. Illness is produced by any of the four dengue
      virus serotypes. A global strategy aimed at increasing the capacity for
      surveillance and outbreak response, changing behaviours and reducing the disease
      burden using integrated vector management in conjunction with early and accurate
      diagnosis has been advocated. Antiviral drugs and vaccines that are currently
      under development could also make an important contribution to dengue control in
      the future.

PMID- 21079657
TI  - Expression of ROR1 in patients with renal cancer--a potential diagnostic marker.
AB  - BACKGROUND: The ectopic expression of receptor tyrosine kinase Ror1 has been
      reported in patients with hematological malignancies such as chronic lymphocytic
      leukemia and acute lymphoblastic leukemia. Here we report, for the first time,
      expression of ROR1 gene in both tumor tissues and peripheral blood mononuclear
      cells (PBMC) from patients with renal cancer (RC). METHODS: In the current study,
      the expression of ROR1 gene was semi-quantitatively measured in PBMC and tumor
      tissues from 16 RC patients as well as PBMC from 22 healthy individuals relative
      to the expression of the housekeeping gene phosphoglucomutase 1 by RT-PCR.
      RESULTS: Our results showed that ROR1 was expressed at gene level in 81.3 percent
      of renal tumor tissues (13 out of 16) whereas it was expressed in 94 percent of
      PBMC from RC patients (15 out of 16). A weak expression of ROR1 was observed in
      PBMC of 4 out of 22 healthy individual. A significant expression of ROR1 was
      observed in PBMC from RC patients when compared to that in PBMC from normal
      healthy individuals (P less than 0.001). The expression of ROR1 in PBMC may
      reflect a shedding of tumor cells into blood stream. CONCLUSION: We conclude that
      detection of a high level of ROR1 expression in blood cells might assist in early
      detection of renal malignancies, providing taking into consideration the clinical
      symptoms of the disease.

PMID- 21079658
TI  - Localization of herpes simplex virus type 1 DNA in latently infected BALB/c mice
      neurons using in situ polymerase chain reaction.
AB  - BACKGROUND: Herpes simplex virus type-1 (HSV-1) establishes a lifelong latent
      infection in neurons following primary infection. The existence of latent HSV-1
      DNA in the trigeminal ganglia of infected BALB/c mice was examined using a direct
      in situ PCR technique, based on Digoxigenin-11-dUTP detection system with anti
      digoxigenin-peroxidase and 3,3'-diaminobenzidine (DAB) substrate. METHODS: Eight
      week-old male BALB/c mice were inoculated via the eye by 104 plaque forming unit
      of wild type Iranian isolates of HSV-1. After establishment of latency,
      trigeminal ganglia were removed and examined using in situ PCR to detect HSV-1
      genome. Finally, the results of in situ PCR were verified by a two-round PCR
      method, using amplification cocktail of in situ reaction, as a template for a
      conventional gel base PCR. RESULTS AND CONCLUSION: The results suggest that a
      direct in situ PCR method using a peroxidase and DAB detection system is a useful
      means for detection of latent HSV-1 DNA in the latently infected ganglia.

PMID- 21079659
TI  - Association between ABCB1-T1236C polymorphism and drug-resistant epilepsy in
      Iranian female patients.
AB  - BACKGROUND: One third of epileptic patients are resistant to several anti
      epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by
      ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from
      the cells and plays a significant role in AEDs resistance. Over-expression of P
      gp could be a result of polymorphisms in ABCB1 gene. We studied the association
      of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug
      resistant epilepsy in Iranian epileptics. METHODS: DNA samples were obtained from
      200 healthy controls and 332 epileptic patients, of whom 200 were drug responsive
      and 132 drug resistant. The frequencies of the genotypes of the two SNP were
      determined by polymerase chain reaction followed by restriction fragment length
      polymorphism. RESULTS: No significant association was found between T129C and
      T1236C genotypes and drug-resistant epilepsy neither in adults nor in children.
      However, the risk of drug resistance was higher in female patients with 1236CC (P
      = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of
      drug resistance was also higher in patients with symptomatic epilepsies with
      1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The
      risk of drug resistance was lower in patients with idiopathic epilepsies with
      129TT genotype (P = 0.001) than in those with CT genotype. CONCLUSION: Our
      results indicate that T1236C polymorphism is associated with drug resistance in
      Iranian female epileptic patients. Replication studies with large sample sizes
      are needed to confirm our results.

PMID- 21079660
TI  - Molecular cloning, expression and enzymatic assay of pteridine reductase 1 from
      Iranian lizard Leishmania.
AB  - BACKGROUND: Currently, there are no effective vaccines against leishmaniasis, and
      treatment using pentavalent antimonial drugs is occasionally effective and often
      toxic for patients. The PTR1 enzyme, which causes antifolate drug resistance in
      Leishmania parasites encoded by gene pteridine reductase 1 (ptr1). Since
      Leishmania lacks pteridine and folate metabolism, it cannot synthesize the
      pteridine moiety from guanine triphosphate. Therefore, it must produce pteridine
      using PTR1, an essential part of the salvage pathway that reduces oxidized
      pteridines. Thus, PTR1 is a good drug-target candidate for anti-Leishmania
      chemotherapy. The aim of this study was the cloning, expression, and enzymatic
      assay of the ptr1 gene from Iranian lizard Leishmania as a model for further
      studies on Leishmania. METHODS: Promastigote DNA was extracted from the Iranian
      lizard Leishmania, and the ptr1 gene was amplified using specific primers. The
      PCR product was cloned, transformed into Escherichia coli strain JM109, and
      expressed. The recombinant protein (PTR1 enzyme) was then purified and assayed.
      RESULTS: ptr1 gene was successfully amplified and cloned into expression vector.
      Recombinant protein (PTR1 enzyme) was purified using affinity chromatography and
      confirmed by Western-blot and dot blot using anti-Leishmania major PTR1 antibody
      and anti-T7 tag monoclonal antibody, respectively. The enzymatic assay was
      confirmed as PTR1 witch performed using 6-biopterin as a substrate and
      nicotinamide adenine dinucleotide phosphate as a coenzyme. CONCLUSION: Iranian
      lizard Leishmania ptr1 was expressed and enzymatic assay was performed
      successfully.

PMID- 21079661
TI  - Effects of leukemia inhibitory factor on gp130 expression and rate of metaphase
      II development during in vitro maturation of mouse oocyte.
AB  - BACKGROUND: Leukemia inhibitory factor (LIF) is a 45-56 kDa glycoprotein that has
      an important role in proliferation and embryo implantation. Its effect on oocyte
      maturation and how to exert the function remained to be elucidated. METHODS:
      Immature mice superovulated with human menopausal gonadotropin and germinal
      vesicle (GV) oocytes were obtained from ovary 48 hours after. GV oocytes were
      cultured in tissue culture medium 199 with 0, 100, 500 and 1,000 U/ml LIF.
      Cumulus expansion and in vitro maturation (IVM) rate were assessed after culture.
      For reverse transcriptase PCR, total RNA from GV and metaphase II (MII) oocytes
      were extracted by Trizol reagent. The quantity and quality of RNA were determined
      by spectrophotometry and electrophoresis, respectively. Reverse transcription was
      performed by Super Script III reverse transcriptase with 1 ug of total RNA
      followed by DNase I treatment and heat inactivation. Expression of gp130 was
      determined by RT-PCR. RESULTS: Our results showed that cumulus expansion was
      improved with 1,000 U/ml in culture medium compared to others. GV breakdown and
      MII rate in groups with LIF were higher than control group and were dose
      dependent. In 1,000 U/ml, LIF rate of MII was significantly higher than control
      group (P less than 0.05). Our results also showed that gp130 is expressed neither
      in GV nor in MII oocytes during IVM of mouse oocytes. CONCLUSION: gp130 is
      expressed in human oocyte but not in mouse. Our results suggest that in mouse,
      LIF could affect the oocyte via another receptor or via cumulus cells; however,
      further studies are warranted.

PMID- 21079662
TI  - The correlation between the endometrial integrins and osteopontin expression with
      pinopodes development in ovariectomized mice in response to exogenous steroids
      hormones.
AB  - BACKGROUND: The ovariectomized animals are good models to evaluate the effect of
      different steroid hormone treatments on implantation events and the pattern of
      integrin expression. Therefore, this study was performed to compare the
      expression of integrins and osteopontin (OPN) in correlation with pinopode
      development in ovariectomized mice endometrium which was subjected to steroid
      hormones. METHODS: Ovariectomized mice were subjected to estrogen, progesterone
      and estrogen-progesterone hormones. Their uterine horns were evaluated for
      integrin expression by immunohistochemistry and real-time RT-PCR and for pinopode
      development by transmission and scanning electron microscopic studies. RESULTS:
      No immunostaining for integrin and OPN molecules were detected in the endometrium
      of non-ovariectomized mice except in metestrus phase. The alpha4 and beta1
      integrin genes were expressed in all phases of estrous cycle. In ovariectomized
      mice, no reaction was detected in the endometrium of control, sham and estrogen
      treated groups, but in both progesterone-treated groups, all examined genes were
      expressed. There was not any correlation between pinopodes and integrin
      expression in ovariectomized mice. CONCLUSION: The progesterone is more effective
      on endometrial integrin expression than estrogen and differences in the
      expression pattern of integrins reflect their important and different roles in
      embryo implantation. The pinopodes may have minor effect in mice implantation or
      have some delay in their expressions in ovariectomized mice which were subjected
      to exogenous hormones.

PMID- 21079663
TI  - Eucalyptus globulus (eucalyptus) treatment of candidiasis in normal and diabetic
      rats.
AB  - BACKGROUND: The leaves of Eucalyptus globulus (eucalyptus) are used for treatment
      of diabetes mellitus in traditional medicine. The aim of this study was to
      evaluate the effects of eucalyptus in treatment of established systemic infection
      with Candida albicans in normal and streptozotocin-induced diabetic rats.
      METHODS: Sixty normoglycemic male Wistar rats, weighing 200-250 g, were selected
      and randomly divided into six groups (n= 10): normal control, control + C.
      albicans, control + eucalyptus + C. albicans, diabetic control, diabetic + C.
      albicans, diabetic + eucalyptus + C. albicans. Diabetes was induced after a
      single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and
      eucalyptus was added to the diet (62.5 g/kg) and drinking water (2.5 g/L) of
      treated animals for 4 weeks. The concerned groups were inoculated with C.
      albicans 15 days after diabetes induction. At the end of one month experiment,
      fasted rats were killed by cervical decapitation. Blood was collected from neck
      vein for estimation of glucose. C. albicans concentrations were estimated in
      liver and kidneys using serial dilution culture of tissue homogenates. RESULTS:
      Eucalyptus administration significantly improved the hyperglycemia, polydipsia,
      polyphagia, and it also compensated weight loss of diabetic rats (P less than
      0.05). Moreover, eucalyptus caused a significant reduction in C. albicans
      concentration in liver and kidney homogenates (P less than 0.01). CONCLUSION: The
      results revealed that eucalyptus improves Candidia infection in normal and
      diabetic rats that in some ways validates the traditional use of this plant in
      treatment of diabetic patients.

PMID- 21079664
TI  - A data-mining approach for multiple structural alignment of proteins.
AB  - Comparing the 3D structures of proteins is an important but computationally hard
      problem in bioinformatics. In this paper, we propose studying the problem when
      much less information or assumptions are available. We model the structural
      alignment of proteins as a combinatorial problem. In the problem, each protein is
      simply a set of points in the 3D space, without sequence order information, and
      the objective is to discover all large enough alignments for any subset of the
      input. We propose a data-mining approach for this problem. We first perform
      geometric hashing of the structures such that points with similar locations in
      the 3D space are hashed into the same bin in the hash table. The novelty is that
      we consider each bin as a coincidence group and mine for frequent patterns, which
      is a well-studied technique in data mining. We observe that these frequent
      patterns are already potentially large alignments. Then a simple heuristic is
      used to extend the alignments if possible. We implemented the algorithm and
      tested it using real protein structures. The results were compared with existing
      tools. They showed that the algorithm is capable of finding conserved
      substructures that do not preserve sequence order, especially those existing in
      protein interfaces. The algorithm can also identify conserved substructures of
      functionally similar structures within a mixture with dissimilar ones. The
      running time of the program was smaller or comparable to that of the existing
      tools.

PMID- 21079665
TI  - Networks of high mutual information define the structural proximity of catalytic
      sites: implications for catalytic residue identification.
AB  - Identification of catalytic residues (CR) is essential for the characterization
      of enzyme function. CR are, in general, conserved and located in the functional
      site of a protein in order to attain their function. However, many non-catalytic
      residues are highly conserved and not all CR are conserved throughout a given
      protein family making identification of CR a challenging task. Here, we put
      forward the hypothesis that CR carry a particular signature defined by networks
      of close proximity residues with high mutual information (MI), and that this
      signature can be applied to distinguish functional from other non-functional
      conserved residues. Using a data set of 434 Pfam families included in the
      catalytic site atlas (CSA) database, we tested this hypothesis and demonstrated
      that MI can complement amino acid conservation scores to detect CR. The Kullback
      Leibler (KL) conservation measurement was shown to significantly outperform both
      the Shannon entropy and maximal frequency measurements. Residues in the proximity
      of catalytic sites were shown to be rich in shared MI. A structural proximity MI
      average score (termed pMI) was demonstrated to be a strong predictor for CR, thus
      confirming the proposed hypothesis. A structural proximity conservation average
      score (termed pC) was also calculated and demonstrated to carry distinct
      information from pMI. A catalytic likeliness score (Cls), combining the KL, pC
      and pMI measures, was shown to lead to significantly improved prediction
      accuracy. At a specificity of 0.90, the Cls method was found to have a
      sensitivity of 0.816. In summary, we demonstrate that networks of residues with
      high MI provide a distinct signature on CR and propose that such a signature
      should be present in other classes of functional residues where the requirement
      to maintain a particular function places limitations on the diversification of
      the structural environment along the course of evolution.

PMID- 21079667
TI  - Infectious disease modeling of social contagion in networks.
AB  - Many behavioral phenomena have been found to spread interpersonally through
      social networks, in a manner similar to infectious diseases. An important
      difference between social contagion and traditional infectious diseases, however,
      is that behavioral phenomena can be acquired by non-social mechanisms as well as
      through social transmission. We introduce a novel theoretical framework for
      studying these phenomena (the SISa model) by adapting a classic disease model to
      include the possibility for 'automatic' (or 'spontaneous') non-social infection.
      We provide an example of the use of this framework by examining the spread of
      obesity in the Framingham Heart Study Network. The interaction assumptions of the
      model are validated using longitudinal network transmission data. We find that
      the current rate of becoming obese is 2 per year and increases by 0.5 percentage
      points for each obese social contact. The rate of recovering from obesity is 4
      per year, and does not depend on the number of non-obese contacts. The model
      predicts a long-term obesity prevalence of approximately 42, and can be used to
      evaluate the effect of different interventions on steady-state obesity. Model
      predictions quantitatively reproduce the actual historical time course for the
      prevalence of obesity. We find that since the 1970s, the rate of recovery from
      obesity has remained relatively constant, while the rates of both spontaneous
      infection and transmission have steadily increased over time. This suggests that
      the obesity epidemic may be driven by increasing rates of becoming obese, both
      spontaneously and transmissively, rather than by decreasing rates of losing
      weight. A key feature of the SISa model is its ability to characterize the
      relative importance of social transmission by quantitatively comparing rates of
      spontaneous versus contagious infection. It provides a theoretical framework for
      studying the interpersonal spread of any state that may also arise spontaneously,
      such as emotions, behaviors, health states, ideas or diseases with reservoirs.

PMID- 21079666
TI  - Monte Carlo analysis of neck linker extension in kinesin molecular motors.
AB  - Kinesin stepping is thought to involve both concerted conformational changes and
      diffusive movement, but the relative roles played by these two processes are not
      clear. The neck linker docking model is widely accepted in the field, but the
      remainder of the step--diffusion of the tethered head to the next binding site-
      is often assumed to occur rapidly with little mechanical resistance. Here, we
      investigate the effect of tethering by the neck linker on the diffusive movement
      of the kinesin head, and focus on the predicted behavior of motors with naturally
      or artificially extended neck linker domains. The kinesin chemomechanical cycle
      was modeled using a discrete-state Markov chain to describe chemical transitions.
      Brownian dynamics were used to model the tethered diffusion of the free head,
      incorporating resistive forces from the neck linker and a position-dependent
      microtubule binding rate. The Brownian dynamics and chemomechanical cycle were
      coupled to model processive runs consisting of many 8 nm steps. Three mechanical
      models of the neck linker were investigated: Constant Stiffness (a simple
      spring), Increasing Stiffness (analogous to a Worm-Like Chain), and Reflecting
      (negligible stiffness up to a limiting contour length). Motor velocities and run
      lengths from simulated paths were compared to experimental results from Kinesin-1
      and a mutant containing an extended neck linker domain. When tethered by an
      increasingly stiff spring, the head is predicted to spend an unrealistically
      short amount of time within the binding zone, and extending the neck is predicted
      to increase both the velocity and processivity, contrary to experiments. These
      results suggest that the Worm-Like Chain is not an adequate model for the
      flexible neck linker domain. The model can be reconciled with experimental data
      if the neck linker is either much more compliant or much stiffer than generally
      assumed, or if weak kinesin-microtubule interactions stabilize the diffusing head
      near its binding site.

PMID- 21079668
TI  - Evaluating gene expression dynamics using pairwise RNA FISH data.
AB  - Recently, a novel approach has been developed to study gene expression in single
      cells with high time resolution using RNA Fluorescent In Situ Hybridization
      (FISH). The technique allows individual mRNAs to be counted with high accuracy in
      wild-type cells, but requires cells to be fixed; thus, each cell provides only a
      "snapshot" of gene expression. Here we show how and when RNA FISH data on pairs
      of genes can be used to reconstruct real-time dynamics from a collection of such
      snapshots. Using maximum-likelihood parameter estimation on synthetically
      generated, noisy FISH data, we show that dynamical programs of gene expression,
      such as cycles (e.g., the cell cycle) or switches between discrete states, can be
      accurately reconstructed. In the limit that mRNAs are produced in short-lived
      bursts, binary thresholding of the FISH data provides a robust way of
      reconstructing dynamics. In this regime, prior knowledge of the type of dynamics-
      cycle versus switch--is generally required and additional constraints, e.g., from
      triplet FISH measurements, may also be needed to fully constrain all parameters.
      As a demonstration, we apply the thresholding method to RNA FISH data obtained
      from single, unsynchronized cells of Saccharomyces cerevisiae. Our results
      support the existence of metabolic cycles and provide an estimate of global gene
      expression noise. The approach to FISH data presented here can be applied in
      general to reconstruct dynamics from snapshots of pairs of correlated quantities
      including, for example, protein concentrations obtained from immunofluorescence
      assays.

PMID- 21079670
TI  - Conflict between noise and plasticity in yeast.
AB  - Gene expression responds to changes in conditions but also stochastically among
      individuals. In budding yeast, both expression responsiveness across conditions
      ("plasticity") and cell-to-cell variation ("noise") have been quantified for
      thousands of genes and found to correlate across genes. It has been argued
      therefore that noise and plasticity may be strongly coupled and mechanistically
      linked. This is consistent with some theoretical ideas, but a strong coupling
      between noise and plasticity also has the potential to introduce cost-benefit
      conflicts during evolution. For example, if high plasticity is beneficial (genes
      need to respond to the environment), but noise is detrimental (fluctuations are
      harmful), then strong coupling should be disfavored. Here, evidence is presented
      that cost-benefit conflicts do occur and that they constrain the evolution of
      gene expression and promoter usage. In contrast to recent assertions, coupling
      between noise and plasticity is not a general property, but one associated with
      particular mechanisms of transcription initiation. Further, promoter
      architectures associated with coupling are avoided when noise is most likely to
      be detrimental, and noise and plasticity are largely independent traits for core
      cellular components. In contrast, when genes are duplicated noise-plasticity
      coupling increases, consistent with reduced detrimental affects of expression
      variation. Noise-plasticity coupling is, therefore, an evolvable trait that may
      constrain the emergence of highly responsive gene expression and be selected
      against during evolution. Further, the global quantitative data in yeast suggest
      that one mechanism that relieves the constraints imposed by noise-plasticity
      coupling is gene duplication, providing an example of how duplication can
      facilitate escape from adaptive conflicts.

PMID- 21079669
TI  - Scalable rule-based modelling of allosteric proteins and biochemical networks.
AB  - Much of the complexity of biochemical networks comes from the information
      processing abilities of allosteric proteins, be they receptors, ion-channels,
      signalling molecules or transcription factors. An allosteric protein can be
      uniquely regulated by each combination of input molecules that it binds. This
      "regulatory complexity" causes a combinatorial increase in the number of
      parameters required to fit experimental data as the number of protein
      interactions increases. It therefore challenges the creation, updating, and re
      use of biochemical models. Here, we propose a rule-based modelling framework that
      exploits the intrinsic modularity of protein structure to address regulatory
      complexity. Rather than treating proteins as "black boxes", we model their
      hierarchical structure and, as conformational changes, internal dynamics. By
      modelling the regulation of allosteric proteins through these conformational
      changes, we often decrease the number of parameters required to fit data, and so
      reduce over-fitting and improve the predictive power of a model. Our method is
      thermodynamically grounded, imposes detailed balance, and also includes molecular
      cross-talk and the background activity of enzymes. We use our Allosteric Network
      Compiler to examine how allostery can facilitate macromolecular assembly and how
      competitive ligands can change the observed cooperativity of an allosteric
      protein. We also develop a parsimonious model of G protein-coupled receptors that
      explains functional selectivity and can predict the rank order of potency of
      agonists acting through a receptor. Our methodology should provide a basis for
      scalable, modular and executable modelling of biochemical networks in systems and
      synthetic biology.

PMID- 21079671
TI  - Intrinsic stability of temporally shifted spike-timing dependent plasticity.
AB  - Spike-timing dependent plasticity (STDP), a widespread synaptic modification
      mechanism, is sensitive to correlations between presynaptic spike trains and it
      generates competition among synapses. However, STDP has an inherent instability
      because strong synapses are more likely to be strengthened than weak ones,
      causing them to grow in strength until some biophysical limit is reached. Through
      simulations and analytic calculations, we show that a small temporal shift in the
      STDP window that causes synchronous, or nearly synchronous, pre- and postsynaptic
      action potentials to induce long-term depression can stabilize synaptic
      strengths. Shifted STDP also stabilizes the postsynaptic firing rate and can
      implement both Hebbian and anti-Hebbian forms of competitive synaptic plasticity.
      Interestingly, the overall level of inhibition determines whether plasticity is
      Hebbian or anti-Hebbian. Even a random symmetric jitter of a few milliseconds in
      the STDP window can stabilize synaptic strengths while retaining these features.
      The same results hold for a shifted version of the more recent "triplet" model of
      STDP. Our results indicate that the detailed shape of the STDP window function
      near the transition from depression to potentiation is of the utmost importance
      in determining the consequences of STDP, suggesting that this region warrants
      further experimental study.

PMID- 21079672
TI  - The cellular robustness by genetic redundancy in budding yeast.
AB  - The frequent dispensability of duplicated genes in budding yeast is heralded as a
      hallmark of genetic robustness contributed by genetic redundancy. However,
      theoretical predictions suggest such backup by redundancy is evolutionarily
      unstable, and the extent of genetic robustness contributed from redundancy
      remains controversial. It is anticipated that, to achieve mutual buffering, the
      duplicated paralogs must at least share some functional overlap. However, counter
      intuitively, several recent studies reported little functional redundancy between
      these buffering duplicates. The large yeast genetic interactions released
      recently allowed us to address these issues on a genome-wide scale. We herein
      characterized the synthetic genetic interactions for ~500 pairs of yeast
      duplicated genes originated from either whole-genome duplication (WGD) or small
      scale duplication (SSD) events. We established that functional redundancy between
      duplicates is a pre-requisite and thus is highly predictive of their backup
      capacity. This observation was particularly pronounced with the use of a newly
      introduced metric in scoring functional overlap between paralogs on the basis of
      gene ontology annotations. Even though mutual buffering was observed to be
      prevalent among duplicated genes, we showed that the observed backup capacity is
      largely an evolutionarily transient state. The loss of backup capacity generally
      follows a neutral mode, with the buffering strength decreasing in proportion to
      divergence time, and the vast majority of the paralogs have already lost their
      backup capacity. These observations validated previous theoretic predictions
      about instability of genetic redundancy. However, departing from the general
      neutral mode, intriguingly, our analysis revealed the presence of natural
      selection in stabilizing functional overlap between SSD pairs. These selected
      pairs, both WGD and SSD, tend to have decelerated functional evolution, have
      higher propensities of co-clustering into the same protein complexes, and share
      common interacting partners. Our study revealed the general principles for the
      long-term retention of genetic redundancy.

PMID- 21079673
TI  - The Mycobacterium tuberculosis drugome and its polypharmacological implications.
AB  - We report a computational approach that integrates structural bioinformatics,
      molecular modelling and systems biology to construct a drug-target network on a
      structural proteome-wide scale. The approach has been applied to the genome of
      Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most
      widely spread infectious diseases. The resulting drug-target interaction network
      for all structurally characterized approved drugs bound to putative M.tb
      receptors, we refer to as the 'TB-drugome'. The TB-drugome reveals that
      approximately one-third of the drugs examined have the potential to be
      repositioned to treat tuberculosis and that many currently unexploited M.tb
      receptors may be chemically druggable and could serve as novel anti-tubercular
      targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on
      the controversial issues surrounding drug-target networks [1]-[3]. Indeed, our
      results support the idea that drug-target networks are inherently modular, and
      further that any observed randomness is mainly caused by biased target coverage.
      The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a
      valuable resource in the development of safe and efficient anti-tubercular drugs.
      More generally the methodology may be applied to other pathogens of interest with
      results improving as more of their structural proteomes are determined through
      the continued efforts of structural biology/genomics.

PMID- 21079674
TI  - Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a
      major metabolic gene.
AB  - Bacterial survival requires adaptation to different environmental perturbations
      such as exposure to antibiotics, changes in temperature or oxygen levels, DNA
      damage, and alternative nutrient sources. During adaptation, bacteria often
      develop beneficial mutations that confer increased fitness in the new
      environment. Adaptation to the loss of a major non-essential gene product that
      cripples growth, however, has not been studied at the whole-genome level. We
      investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of
      phosphoglucose isomerase (pgi) by adaptively evolving ten replicates of E. coli
      lacking pgi for 50 days in glucose M9 minimal medium and by characterizing
      endpoint clones through whole-genome re-sequencing and phenotype profiling. We
      found that 1) the growth rates for all ten endpoint clones increased
      approximately 3-fold over the 50-day period; 2) two to five mutations arose
      during adaptation, most frequently in the NADH/NADPH transhydrogenases udhA and
      pntAB and in the stress-associated sigma factor rpoS; and 3) despite similar
      growth rates, at least three distinct endpoint phenotypes developed as defined by
      different rates of acetate and formate secretion. These results demonstrate that
      E. coli can adapt to the loss of a major metabolic gene product with only a
      handful of mutations and that adaptation can result in multiple, alternative
      phenotypes.

PMID- 21079675
TI  - Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T
      lymphocytes.
AB  - HIV-1 escape from the cytotoxic T-lymphocyte (CTL) response leads to a weakening
      of viral control and is likely to be detrimental to the patient. To date, the
      impact of escape on viral load and CD4(+) T cell count has not been quantified,
      primarily because of sparse longitudinal data and the difficulty of separating
      cause and effect in cross-sectional studies. We use two independent methods to
      quantify the impact of HIV-1 escape from CTLs in chronic infection: mathematical
      modelling of escape and statistical analysis of a cross-sectional cohort.
      Mathematical modelling revealed a modest increase in log viral load of 0.051
      copies ml(-1) per escape event. Analysis of the cross-sectional cohort revealed a
      significant positive association between viral load and the number of "escape
      events", after correcting for length of infection and rate of replication. We
      estimate that a single CTL escape event leads to a viral load increase of 0.11
      log copies ml(-1) (95% confidence interval: 0.040-0.18), consistent with the
      predictions from the mathematical modelling. Overall, the number of escape events
      could only account for approximately 6% of the viral load variation in the
      cohort. Our findings indicate that although the loss of the CTL response for a
      single epitope results in a highly statistically significant increase in viral
      load, the biological impact is modest. We suggest that this small increase in
      viral load is explained by the small growth advantage of the variant relative to
      the wildtype virus. Escape from CTLs had a measurable, but unexpectedly low,
      impact on viral load in chronic infection.

PMID- 21079676
TI  - Shunting inhibition controls the gain modulation mediated by asynchronous
      neurotransmitter release in early development.
AB  - The sensitivity of a neuron to its input can be modulated in several ways.
      Changes in the slope of the neuronal input-output curve depend on factors such as
      shunting inhibition, background noise, frequency-dependent synaptic excitation,
      and balanced excitation and inhibition. However, in early development GABAergic
      interneurons are excitatory and other mechanisms such as asynchronous transmitter
      release might contribute to regulating neuronal sensitivity. We modeled both
      phasic and asynchronous synaptic transmission in early development to study the
      impact of activity-dependent noise and short-term plasticity on the synaptic
      gain. Asynchronous release decreased or increased the gain depending on the
      membrane conductance. In the high shunt regime, excitatory input due to
      asynchronous release was divisive, whereas in the low shunt regime it had a
      nearly multiplicative effect on the firing rate. In addition, sensitivity to
      correlated inputs was influenced by shunting and asynchronous release in opposite
      ways. Thus, asynchronous release can regulate the information flow at synapses
      and its impact can be flexibly modulated by the membrane conductance.

PMID- 21079677
TI  - Hormad1 mutation disrupts synaptonemal complex formation, recombination, and
      chromosome segregation in mammalian meiosis.
AB  - Meiosis is unique to germ cells and essential for reproduction. During the first
      meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The
      homologues connect via axial elements and numerous transverse filaments to form
      the synaptonemal complex. The synaptonemal complex is a critical component for
      chromosome pairing, segregation, and recombination. We previously identified a
      novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the
      synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA
      domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout
      male and female mice are infertile. Hormad1 deficient (Hormad1(-/) (-)) testes
      exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes
      cannot be visualized by electron microscopy. Hormad1 deficiency does not affect
      localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but
      disrupts homologous chromosome pairing. Double stranded break formation and early
      recombination events are disrupted in Hormad1(-/) (-) testes and ovaries as shown
      by the drastic decrease in the gammaH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co
      localizes with gammaH2AX to the sex body during pachytene. BRCA1, ATR, and
      gammaH2AX co-localize to the sex body and participate in meiotic sex chromosome
      inactivation and transcriptional silencing. Hormad1 deficiency abolishes
      gammaH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes
      transcriptional de-repression on the X chromosome. Unlike testes, Hormad1(-/) (-)
      ovaries have seemingly normal ovarian folliculogenesis after puberty. However,
      embryos generated from Hormad1(-/) (-) oocytes are hyper- and hypodiploid at the
      2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is
      therefore a critical component of the synaptonemal complex that affects synapsis,
      recombination, and meiotic sex chromosome inactivation and transcriptional
      silencing.

PMID- 21079678
TI  - Exploring the universe of protein structures beyond the Protein Data Bank.
AB  - It is currently believed that the atlas of existing protein structures is
      faithfully represented in the Protein Data Bank. However, whether this atlas
      covers the full universe of all possible protein structures is still a highly
      debated issue. By using a sophisticated numerical approach, we performed an
      exhaustive exploration of the conformational space of a 60 amino acid polypeptide
      chain described with an accurate all-atom interaction potential. We generated a
      database of around 30,000 compact folds with at least of secondary structure
      corresponding to local minima of the potential energy. This ensemble plausibly
      represents the universe of protein folds of similar length; indeed, all the known
      folds are represented in the set with good accuracy. However, we discover that
      the known folds form a rather small subset, which cannot be reproduced by
      choosing random structures in the database. Rather, natural and possible folds
      differ by the contact order, on average significantly smaller in the former. This
      suggests the presence of an evolutionary bias, possibly related to kinetic
      accessibility, towards structures with shorter loops between contacting residues.
      Beside their conceptual relevance, the new structures open a range of practical
      applications such as the development of accurate structure prediction strategies,
      the optimization of force fields, and the identification and design of novel
      folds.

PMID- 21079679
TI  - Compensation for changing motor uncertainty.
AB  - When movement outcome differs consistently from the intended movement, errors are
      used to correct subsequent movements (e.g., adaptation to displacing prisms or
      force fields) by updating an internal model of motor and/or sensory systems.
      Here, we examine changes to an internal model of the motor system under changes
      in the variance structure of movement errors lacking an overall bias. We
      introduced a horizontal visuomotor perturbation to change the statistical
      distribution of movement errors anisotropically, while monetary gains/losses were
      awarded based on movement outcomes. We derive predictions for simulated movement
      planners, each differing in its internal model of the motor system. We find that
      humans optimally respond to the overall change in error magnitude, but ignore the
      anisotropy of the error distribution. Through comparison with simulated movement
      planners, we found that aimpoints corresponded quantitatively to an ideal
      movement planner that updates a strictly isotropic (circular) internal model of
      the error distribution. Aimpoints were planned in a manner that ignored the
      direction-dependence of error magnitudes, despite the continuous availability of
      unambiguous information regarding the anisotropic distribution of actual motor
      errors.

PMID- 21079680
TI  - Genome-wide effects of long-term divergent selection.
AB  - To understand the genetic mechanisms leading to phenotypic differentiation, it is
      important to identify genomic regions under selection. We scanned the genome of
      two chicken lines from a single trait selection experiment, where 50 generations
      of selection have resulted in a 9-fold difference in body weight. Analyses of
      nearly 60,000 SNP markers showed that the effects of selection on the genome are
      dramatic. The lines were fixed for alternative alleles in more than 50 regions as
      a result of selection. Another 10 regions displayed strong evidence for ongoing
      differentiation during the last 10 generations. Many more regions across the
      genome showed large differences in allele frequency between the lines, indicating
      that the phenotypic evolution in the lines in 50 generations is the result of an
      exploitation of standing genetic variation at 100s of loci across the genome.

PMID- 21079681
TI  - Human-specific evolution and adaptation led to major qualitative differences in
      the variable receptors of human and chimpanzee natural killer cells.
AB  - Natural killer (NK) cells serve essential functions in immunity and reproduction.
      Diversifying these functions within individuals and populations are rapidly
      evolving interactions between highly polymorphic major histocompatibility complex
      (MHC) class I ligands and variable NK cell receptors. Specific to simian primates
      is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize
      MHC class I and associate with a range of human diseases. Because KIR have
      considerable species-specificity and are lacking from common animal models, we
      performed extensive comparison of the systems of KIR and MHC class I interaction
      in humans and chimpanzees. Although of similar complexity, they differ in genomic
      organization, gene content, and diversification mechanisms, mainly because of
      human-specific specialization in the KIR that recognizes the C1 and C2 epitopes
      of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing
      C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to
      unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of
      ancient, avid, and predominantly inhibitory receptors, whereas human receptors
      are fewer, recently evolved, and combine avid inhibitory receptors with
      attenuated activating receptors. These differences accompany human-specific
      evolution of the A and B haplotypes that are under balancing selection and
      differentially function in defense and reproduction. Our study shows how the
      qualitative differences that distinguish the human and chimpanzee systems of KIR
      and MHC class I predominantly derive from adaptations on the human line in
      response to selective pressures placed on human NK cells by the competing needs
      of defense and reproduction.

PMID- 21079682
TI  - Coding "what" and "when" in the Archer fish retina.
AB  - Traditionally, the information content of the neural response is quantified using
      statistics of the responses relative to stimulus onset time with the assumption
      that the brain uses onset time to infer stimulus identity. However, stimulus
      onset time must also be estimated by the brain, making the utility of such an
      approach questionable. How can stimulus onset be estimated from the neural
      responses with sufficient accuracy to ensure reliable stimulus identification? We
      address this question using the framework of colour coding by the archer fish
      retinal ganglion cell. We found that stimulus identity, "what", can be estimated
      from the responses of best single cells with an accuracy comparable to that of
      the animal's psychophysical estimation. However, to extract this information, an
      accurate estimation of stimulus onset is essential. We show that stimulus onset
      time, "when", can be estimated using a linear-nonlinear readout mechanism that
      requires the response of a population of 100 cells. Thus, stimulus onset time can
      be estimated using a relatively simple readout. However, large nerve cell
      populations are required to achieve sufficient accuracy.

PMID- 21079683
TI  - Tyrosine sulfation of the amino terminus of PSGL-1 is critical for enterovirus 71
      infection.
AB  - Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and
      mouth disease, a common febrile disease in children; however, EV71 has been also
      associated with various neurological diseases including fatal cases in large EV71
      outbreaks particularly in the Asia Pacific region. Recently we identified human P
      selectin glycoprotein ligand-1 (PSGL-1) as a cellular receptor for entry and
      replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the
      surface of leukocytes, serves as a high affinity counterreceptor for selectins,
      and mediates leukocyte rolling on the endothelium. The PSGL-1-P-selectin
      interaction requires sulfation of at least one of three clustered tyrosines and
      an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1.
      To elucidate the molecular basis of the PSGL-1-EV71 interaction, we generated a
      series of PSGL-1 mutants and identified the post-translational modifications that
      are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in
      293T cells and the transfected cells were assayed for their abilities to bind to
      EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical
      for PSGL-1-selectin interaction, is not necessary for PSGL-1 binding to EV71. On
      the other hand, site-directed mutagenesis at one or more potential tyrosine
      sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1
      binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked
      the PSGL-1-EV71 interaction and inhibited PSGL-1-mediated viral replication of
      EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in
      this study reveal that tyrosine sulfation, but not O-glycosylation, in the N
      terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in
      leukocytes.

PMID- 21079684
TI  - ATM limits incorrect end utilization during non-homologous end joining of
      multiple chromosome breaks.
AB  - Chromosome rearrangements can form when incorrect ends are matched during end
      joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We
      tested whether the ATM kinase limits chromosome rearrangements via suppressing
      incorrect end utilization during EJ repair of multiple DSBs. For this, we
      developed a system for monitoring EJ of two tandem DSBs that can be repaired
      using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss
      of the DNA between the DSBs). In this system, two DSBs are induced in a
      chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into
      non-cohesive ends by the exonuclease Trex2, which leads to the formation of I
      SceI-resistant EJ products during both Proximal-EJ and Distal-EJ. Using this
      method, we find that genetic or chemical disruption of ATM causes a substantial
      increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in
      Distal-EJ caused by ATM disruption is dependent on classical non-homologous end
      joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present
      evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal
      EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of
      these factors on end processing, we examined Distal-EJ repair junctions. We found
      that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs
      promote short deletions. Thus, the regulation of end processing appears distinct
      from that of end utilization. In summary, we suggest that ATM is important to
      limit incorrect end utilization during c-NHEJ.

PMID- 21079685
TI  - Translation elongation factor 1A facilitates the assembly of the tombusvirus
      replicase and stimulates minus-strand synthesis.
AB  - Replication of plus-strand RNA viruses depends on host factors that are recruited
      into viral replicase complexes. Previous studies showed that eukaryotic
      translation elongation factor (eEF1A) is one of the resident host proteins in the
      highly purified tombusvirus replicase complex. Using a random library of eEF1A
      mutants, we identified one mutant that decreased and three mutants that increased
      Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in
      vitro assays with whole cell extracts prepared from yeast strains expressing the
      eEF1A mutants demonstrated several functions for eEF1A in TBSV replication:
      facilitating the recruitment of the viral RNA template into the replicase
      complex; the assembly of the viral replicase complex; and enhancement of the
      minus-strand synthesis by promoting the initiation step. These roles for eEF1A
      are separate from its canonical role in host and viral protein translation,
      emphasizing critical functions for this abundant cellular protein during TBSV
      replication.

PMID- 21079686
TI  - Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and
      zinc ionophores block the replication of these viruses in cell culture.
AB  - Increasing the intracellular Zn(2+) concentration with zinc-ionophores like
      pyrithione (PT) can efficiently impair the replication of a variety of RNA
      viruses, including poliovirus and influenza virus. For some viruses this effect
      has been attributed to interference with viral polyprotein processing. In this
      study we demonstrate that the combination of Zn(2+) and PT at low concentrations
      (2 uM Zn(2+) and 2 uM PT) inhibits the replication of SARS-coronavirus (SARS-CoV)
      and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two
      distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase
      (RdRp), which is the core enzyme of their multiprotein replication and
      transcription complex (RTC). Using an activity assay for RTCs isolated from cells
      infected with SARS-CoV or EAV--thus eliminating the need for PT to transport
      Zn(2+) across the plasma membrane--we show that Zn(2+) efficiently inhibits the
      RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using
      recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli
      subsequently revealed that Zn(2+) directly inhibited the in vitro activity of
      both nidovirus polymerases. More specifically, Zn(2+) was found to block the
      initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp
      elongation was inhibited and template binding reduced. By chelating Zn(2+) with
      MgEDTA, the inhibitory effect of the divalent cation could be reversed, which
      provides a novel experimental tool for in vitro studies of the molecular details
      of nidovirus replication and transcription.

PMID- 21079687
TI  - Autoimmunity as a predisposition for infectious diseases.

PMID- 21079688
TI  - HTLV-1 evades type I interferon antiviral signaling by inducing the suppressor of
      cytokine signaling 1 (SOCS1).
AB  - Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of Adult T
      cell Leukemia (ATL) and the neurological disorder HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV
      1-infected individuals remain asymptomatic carriers (AC) during their lifetime, 2
      5% will develop either ATL or HAM/TSP, but never both. To better understand the
      gene expression changes in HTLV-1-associated diseases, we examined the mRNA
      profiles of CD4+ T cells isolated from 7 ATL, 12 HAM/TSP, 11 AC and 8 non
      infected controls. Using genomic approaches followed by bioinformatic analysis,
      we identified gene expression pattern characteristic of HTLV-1 infected
      individuals and particular disease states. Of particular interest, the suppressor
      of cytokine signaling 1--SOCS1--was upregulated in HAM/TSP and AC patients but
      not in ATL. Moreover, SOCS1 was positively correlated with the expression of HTLV
      1 mRNA in HAM/TSP patient samples. In primary PBMCs transfected with a HTLV-1
      proviral clone and in HTLV-1-transformed MT-2 cells, HTLV-1 replication
      correlated with induction of SOCS1 and inhibition of IFN-alpha/beta and IFN
      stimulated gene expression. Targeting SOCS1 with siRNA restored type I IFN
      production and reduced HTLV-1 replication in MT-2 cells. Conversely, exogenous
      expression of SOCS1 resulted in enhanced HTLV-1 mRNA synthesis. In addition to
      inhibiting signaling downstream of the IFN receptor, SOCS1 inhibited IFN-beta
      production by targeting IRF3 for ubiquitination and proteasomal degradation.
      These observations identify a novel SOCS1 driven mechanism of evasion of the type
      I IFN antiviral response against HTLV-1.

PMID- 21079689
TI  - DNA methylation and normal chromosome behavior in Neurospora depend on five
      components of a histone methyltransferase complex, DCDC.
AB  - Methylation of DNA and of Lysine 9 on histone H3 (H3K9) is associated with gene
      silencing in many animals, plants, and fungi. In Neurospora crassa, methylation
      of H3K9 by DIM-5 directs cytosine methylation by recruiting a complex containing
      Heterochromatin Protein-1 (HP1) and the DIM-2 DNA methyltransferase. We report
      genetic, proteomic, and biochemical investigations into how DIM-5 is controlled.
      These studies revealed DCDC, a previously unknown protein complex including DIM
      5, DIM-7, DIM-9, CUL4, and DDB1. Components of DCDC are required for H3K9me3,
      proper chromosome segregation, and DNA methylation. DCDC-defective strains, but
      not HP1-defective strains, are hypersensitive to MMS, revealing an HP1
      independent function of H3K9 methylation. In addition to DDB1, DIM-7, and the
      WD40 domain protein DIM-9, other presumptive DCAFs (DDB1/CUL4 associated factors)
      co-purified with CUL4, suggesting that CUL4/DDB1 forms multiple complexes with
      distinct functions. This conclusion was supported by results of drug sensitivity
      tests. CUL4, DDB1, and DIM-9 are not required for localization of DIM-5 to
      incipient heterochromatin domains, indicating that recruitment of DIM-5 to
      chromatin is not sufficient to direct H3K9me3. DIM-7 is required for DIM-5
      localization and mediates interaction of DIM-5 with DDB1/CUL4 through DIM-9.
      These data support a two-step mechanism for H3K9 methylation in Neurospora.

PMID- 21079690
TI  - Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in
      bronchial epithelium.
AB  - The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA
      helicases RIG-I and MDA5 in viral infection is much debated. We investigated the
      roles of each pattern recognition receptor in rhinovirus infection using primary
      bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and
      MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial
      epithelial tissue from normal volunteers challenged with rhinovirus in vivo
      exhibited low levels of RIG-I and MDA5 that were increased at day 4 post
      infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine
      mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using
      siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient
      mice exhibited RIG-I and MDA5 induction early during RV1B infection in an
      interferon independent manner. Hence anti-viral defense within bronchial
      epithelium requires co-ordinated recognition of rhinovirus infection, initially
      via TLR3/TRIF and later via inducible RNA helicases.

PMID- 21079691
TI  - The female lower genital tract is a privileged compartment with IL-10 producing
      dendritic cells and poor Th1 immunity following Chlamydia trachomatis infection.
AB  - While a primary genital tract infection with C. trachomatis stimulates partial
      protection against re-infection, it may also result in severe inflammation and
      tissue destruction. Here we have dissected whether functional compartments exist
      in the genital tract that restrict Th1-mediated protective immunity. Apart from
      the Th1-subset, little is known about the role of other CD4(+) T cell subsets in
      response to a genital tract chlamydial infection. Therefore, we investigated
      CD4(+) T cell subset differentiation in the genital tract using RT-PCR for
      expression of critical transcription factors and cytokines in the upper (UGT) and
      lower genital tract (LGT) of female C57BL/6 mice in response to C. trachomatis
      serovar D infection. We found that the Th1 subset dominated the UGT, as IFN-gamma
      and T-bet mRNA expression were high, while GATA-3 was low following genital
      infection with C. trachomatis serovar D. By contrast, IL-10 and GATA-3 mRNA
      dominated the LGT, suggesting the presence of Th2 cells. These functional
      compartments also attracted regulatory T cells (Tregs) differently as increased
      FoxP3 mRNA expression was seen primarily in the UGT. Although IL-17A mRNA was
      somewhat up-regulated in the LGT, no significant change in RORgamma-t mRNA
      expression was observed, suggesting no involvement of Th17 cells. The dichotomy
      between the LGT and UGT was maintained during infection by IL-10 because in IL-10
      deficient mice the distinction between the two compartments was completely lost
      and a dramatic shift to the predominance of Th1 cells in the LGT occurred.
      Unexpectedly, the major source of IL-10 was CD11c(+) CD11b(+) DC, probably
      creating an anti-inflammatory privileged site in the LGT.

PMID- 21079692
TI  - The complex genetic architecture of the metabolome.
AB  - Discovering links between the genotype of an organism and its metabolite levels
      can increase our understanding of metabolism, its controls, and the indirect
      effects of metabolism on other quantitative traits. Recent technological advances
      in both DNA sequencing and metabolite profiling allow the use of broad-spectrum,
      untargeted metabolite profiling to generate phenotypic data for genome-wide
      association studies that investigate quantitative genetic control of metabolism
      within species. We conducted a genome-wide association study of natural variation
      in plant metabolism using the results of untargeted metabolite analyses performed
      on a collection of wild Arabidopsis thaliana accessions. Testing 327 metabolites
      against >200,000 single nucleotide polymorphisms identified numerous genotype
      metabolite associations distributed non-randomly within the genome. These
      clusters of genotype-metabolite associations (hotspots) included regions of the
      A. thaliana genome previously identified as subject to recent strong positive
      selection (selective sweeps) and regions showing trans-linkage to these putative
      sweeps, suggesting that these selective forces have impacted genome-wide control
      of A. thaliana metabolism. Comparing the metabolic variation detected within this
      collection of wild accessions to a laboratory-derived population of recombinant
      inbred lines (derived from two of the accessions used in this study) showed that
      the higher level of genetic variation present within the wild accessions did not
      correspond to higher variance in metabolic phenotypes, suggesting that
      evolutionary constraints limit metabolic variation. While a major goal of genome
      wide association studies is to develop catalogues of intraspecific variation, the
      results of multiple independent experiments performed for this study showed that
      the genotype-metabolite associations identified are sensitive to environmental
      fluctuations. Thus, studies of intraspecific variation conducted via genome-wide
      association will require analyses of genotype by environment interaction.
      Interestingly, the network structure of metabolite linkages was also sensitive to
      environmental differences, suggesting that key aspects of network architecture
      are malleable.

PMID- 21079693
TI  - Preliminary Study of the Clinical Hypoglycemic Effects of Allium cepa (Red Onion)
      in Type 1 and Type 2 Diabetic Patients.
AB  - BACKGROUND: Diabetes mellitus is a heterogeneous group of disorders characterized
      by abnormalities of carbohydrate, protein and lipid metabolism. Type 1 diabetes
      mellitus is an autoimmune disease caused by destruction of pancreatic beta cells
      and characterized by defect in insulin secretion while type 2 diabetes mellitus
      results from abnormalities in insulin secretion and/or insulin action or both.
      OBJECTIVES: The present study was conducted to investigate the clinical
      hypoglycemic effects of Allium cepa in type 1 and type 2 diabetic patients.
      RESULTS: In assessment of hypoglycaemic activity of Allium cepa in type 1 and
      type 2 diabetic patients, ingestion of crude Allium cepa (100 g) caused a
      considerable reduction in fasting blood glucose levels by about 89 mg/dl in
      relation to insulin (145 mg/dl) in type 1 diabetic patients and it reduced
      fasting blood glucose levels by 40 mg/dl, compared to glibenclamide (81 mg/dl) in
      type 2 diabetic patients, 4 hours later. The same dose of crude Allium cepa
      produced a significant reduction in the induced hyperglycemia (GTT) by about 120
      mg/dl compared to water (77 mg/dl) and insulin (153 mg/dl) in type 1 diabetic
      patients and considerably reduced GTT by 159 mg/dl in relation to water (55
      mg/dl) and glibenclamide (114 mg/dl) in type 2 diabetic patients, after 4 hours.
      CONCLUSION: It was evident that, crude Allium cepa produced hypoglycemic effects,
      thus it could be used as a dietary supplement in management of type 1 and/or type
      2 diabetes mellitus.

PMID- 21079694
TI  - Air pollution and emergency department visits for suicide attempts in vancouver,
      Canada.
AB  - BACKGROUND: Comorbidity of depression, heart disease, and migraine has been
      observed in clinical practice, while ambient air pollution has been identified
      among different risk factors for these health conditions. Suicide attempts and
      ideations as the result of depression may be linked to air pollution exposure.
      Therefore the effects of ambient air pollution on emergency department (ED)
      visits for suicide attempts were investigated. METHODS: Emergency visit data were
      collected in a hospital in Vancouver, Canada. The generalized linear mixed models
      technique was applied in the analysis of these data. A natural hierarchical
      structure of the data was used to define the clusters, with days nested in a 3
      level structure (day of week, month, year). Poisson models were fitted to the
      clustered counts of ED visits with a single air pollutant, temperature and
      relative humidity. In addition, the case-crossover methodology was used with the
      same data for comparison. The analysis was performed by gender (all, males,
      females) and month (all: January-December, warm: April-September, cold: October
      March). RESULTS: Both hierarchical and case-crossover methods confirmed positive
      and statistically significant associations among carbon monoxide (CO), nitrogen
      dioxide (NO(2)), sulphur dioxide (SO(2)), and particulate matter (PM(10)) for all
      suicide attempts in the cold period. The largest increase was observed for males
      in the cold period for a 1-day lagged exposure to NO(2), with an excess risk of
      23.9% (95% CI: 7.8, 42.4) and odds ratio of 1.21 (95% CI: 1.03, 1.41). In warm
      months the associations were not statistically significant, and the highest
      positive value was obtained for ozone lagged by 1 day. CONCLUSION: The results
      indicate a potential association between air pollution and emergency department
      visits for suicide attempts.

PMID- 21079695
TI  - Using femtosecond laser to fabricate highly precise interior three-dimensional
      microstructures in polymeric flow chip.
AB  - This paper reports using femtosecond laser marker to fabricate the three
      dimensional interior microstructures in one closed flow channel of plastic
      substrate. Strip-like slots in the dimensions of 800 MUm*400 MUm*65 MUm were
      ablated with pulse Ti:sapphire laser at 800 nm (pulse duration of ~120 fs with 1
      kHz repetition rate) on acrylic slide. After ablation, defocused beams were used
      to finish the surface of microstructures. Having finally polished with
      sonication, the laser fabricated structures are highly precise with the
      arithmetic roughness of 1.5 and 4.5 nm. Fabricating such highly precise
      microstructures cannot be accomplished with nanosecond laser marking or other
      mechanical drilling methods. In addition, since laser ablation can directly
      engrave interior microstructures in one closed chip, glue smearing problems to
      damage molded microstructures possibly to occur during the chip sealing
      procedures can be avoided too.

PMID- 21079696
TI  - Prospective durability testing of a vascular access phantom.
AB  - INTRODUCTION: We assessed the acoustic transmission, image quality, and vessel
      integrity of the Blue PhantomTM 2 Vessel Original Ultrasound Training Model with
      repeated use. METHODS: The study consisted of two phases. During the first phase,
      a portion of the Blue PhantomTM rubber matrix (without a simulated vessel) was
      placed over a two-tiered echogenic structure and was repeatedly punctured with a
      hollow bore 18-gauge needle in a 1 cm(2) area. During the second phase, a portion
      of the matrix with a simulated vessel was repeatedly punctured with another
      hollow bore 18-gauge needle. During both phases we obtained an ultrasound image
      using a high-frequency linear probe after every 100 needle punctures to assess
      the effect of repeated needle punctures on image quality, acoustic transmission,
      and simulated vessel integrity. RESULTS: Testing on the rubber matrix alone
      (first phase) without a vessel demonstrated a gradual decrease in image quality
      and visualization of the proximal and distal portions of the target structure,
      but they remained visible after 1,000 needle punctures. The second phase
      demonstrated excellent acoustic transmission and image quality on both transverse
      and longitudinal images of the rubber matrix and simulated vessel after 1,000
      needle punctures. The anterior and posterior vessel walls and needle tip were
      well visualized without any signs of vessel leakage on still images or with
      compression and power Doppler. CONCLUSION: The Blue PhantomTM 2 Vessel Original
      Ultrasound Training Model demonstrated excellent durability after 1,000 needle
      punctures in a 1- cm(2) area. Based on the length of simulated vessel in each
      model, it should support over 25,000 simulated attempts at vascular access.

PMID- 21079697
TI  - Ultrasound diagnosis of bilateral quadriceps tendon rupture after statin use.
AB  - Simultaneous bilateral quadriceps tendon rupture is a rare injury. We report the
      case of bilateral quadriceps tendon rupture sustained with minimal force while
      refereeing a football game. The injury was suspected to be associated with statin
      use as the patient had no other identifiable risk factors. The diagnosis was
      confirmed using bedside ultrasound.

PMID- 21079698
TI  - Ultrasound-guided three-in-one nerve block for femur fractures.
AB  - Femur fractures typically affect elderly patients with multiple co-morbidities.
      Pain control can be difficult, requiring intensive nursing and physician care as
      elderly patients may manifest cardiovascular and respiratory complications from
      opiate administration. Ultrasound (US)-guided three-in-one (3-in-1) femoral nerve
      block (FNB) is an option for pain management in patients with femur fractures, as
      it provides regional anesthesia to the femoral, obturator and lateral cutaneous
      nerves. Our goal is to provide medical education regarding the use of US-guided 3
      in-1FNB as a rapid and easy procedure that may provide optimal patient care in
      patients with femur fractures.

PMID- 21079699
TI  - Variability in Ultrasound Education among Emergency Medicine Residencies.
AB  - OBJECTIVE: Education in emergency ultrasound (EUS) has become an essential part
      of emergency medicine (EM) resident training. In 2009, comprehensive residency
      training guidelines were published to ensure proficiency in ultrasound education.
      The American College of Emergency Physicians (ACEP) recommends that 150
      ultrasound exams be performed for physician competency. Our goal is to evaluate
      the current ultrasound practices among EM residency programs and assess the need
      for further formalization of EUS training. METHODS: We generated a survey using
      an online survey tool and administered via the internet. The survey consisted of
      25 questions that included multiple choice and free text answers. These online
      survey links were sent via email to EM ultrasound directors at all 149 American
      College of Graduate Medical Education EM residency programs in April 2008. We
      surveyed programs regarding EUS curriculum and residency proficiency requirements
      and descriptive statistics were used to report the survey findings. RESULTS:
      Sixty-five residency programs responded to the survey. The average number of
      ultrasound exams required by programs for EUS competency was 137 scans. However,
      the majority of programs 42/65 (64%) require their residents to obtain 150 scans
      or greater for competency. Fifty-one out of 64 (79%) programs reported having a
      structured ultrasound curriculum while 14/64 (21%) of programs reported that EUS
      training is primarily resident self-directed. In terms of faculty credentialing,
      29/62 (47%) of residency programs have greater than 50% of faculty credentialed.
      Forty-four out of 61 (72%) programs make EUS a required rotation. Thirty-four out
      of 63 (54%) programs felt that they were meeting all their goals for resident EUS
      education. CONCLUSION: Currently discrepancies exist between EM residency
      programs in ultrasound curriculum and perceived needs for achieving proficiency
      in EUS. Although a majority of residency programs require 150 ultrasound exams or
      more to achieve resident competency, overall the average number of scans required
      by all programs is 137 exams. This number is less than that recommended by ACEP
      for physician competency. These data suggest that guidelines are needed to help
      standardize ultrasound training for all EM residency programs.

PMID- 21079700
TI  - Ultrasound use and "overuse".
AB  - The U.S. Department of Health and Human Services Office of the Inspector General
      has issued a report concerning "high use" and "questionable use" ultrasound.
      Findings include those geographic areas where occurrences are most frequent, as
      well as the most common elements that characterize questionable use. While not
      its primary focus, emergency physician performed bedside ultrasound is within the
      scope of the report. Implications for emergency ultrasound are discussed and
      practice recommendations made for minimizing regulatory exposure for emergency
      physicians and departments.

PMID- 21079701
TI  - Ultrasound detection of lung hepatization.
AB  - Bedside ultrasound interrogation of the thorax can aide the clinician in
      determining the cause of the respiratory dysfunction. Often plain radiographs are
      not sufficient to differentiate pathology. We present a case in which bedside
      ultrasound defined the pathology without the need for further imaging.

PMID- 21079702
TI  - Occupancy rates and emergency department work index scores correlate with leaving
      without being seen.
AB  - OBJECTIVE: TWO CROWDING METRICS ARE OFTEN USED TO MEASURE EMERGENCY DEPARTMENT
      (ED) CROWDING: the occupancy rate and the emergency department work index (EDWIN)
      score. To evaluate these metrics for applicability in our community ED, we sought
      to measure their correlation with the number of patients who left without being
      seen (LWBS) and determine if either, or both, correlated with our daily LWBS
      rate. We hypothesized a statistically significant positive correlation between
      the number of patients who LWBS and both crowding metrics. METHODS: We performed
      a retrospective observational study by reviewing data on all patients who LWBS
      from December 1, 2007, to February 29, 2008. Occupancy rates and EDWIN scores
      were obtained through our electronic patient tracking board. We identified LWBS
      status by searching the final disposition entered into our electronic medical
      record. We measured the correlation between each crowding metric averaged over
      each 24-hour day and the number of patients who LWBS per 24-hour day using
      Spearman's rank correlation, and created receiver operator characteristic (ROC)
      curves to quantify the discriminatory power of occupancy rate and EDWIN score for
      predicting more than two patients per day who LWBS. RESULTS: We identified 1,193
      patients who LWBS during the study period, including patients who registered but
      then left the waiting room (733), as well as those who left before: registration
      (71), triage (75), seeing a physician (260), or final disposition (54). The
      number of patients who LWBS per day ranged from one to 30, with a mean of 13 and
      median of 11 (IQR 6 to 19). The daily number of patients who LWBS showed a
      positive correlation with the average daily occupancy rate (Spearman's rho =
      0.771, p = 0.01) and with average daily EDWIN score (Spearman's rho = 0.67, p<
      .001). Area under the ROC curve for occupancy rate was .97 (95% CI .93 to 1.0)
      and for EDWIN score was .94 (95% CI .89 to 1.0). CONCLUSION: Average daily
      occupancy rates and EDWIN scores both correlate positively with, and have
      excellent discriminatory power for, the number of patients who LWBS in our ED;
      however, the scale of our EDWIN scores differs from that obtained at other
      institutions. For studies of crowding, occupancy rate may be the more useful
      metric due to its ease of calculation.

PMID- 21079703
TI  - Impact on length of stay after introduction of emergency department information
      system.
AB  - OBJECTIVE: An electronic emergency department information system (EDIS) can
      monitor the progress of a patient visit, facilitate computerized physician order
      entry, display test results and generate an electronic medical record. Ideally,
      use of an EDIS will increase overall emergency department (ED) efficiency.
      However, in academic settings where new interns rotate through the ED monthly,
      the "learning curve" experienced by the new EDIS user may slow down patient care.
      In this study, we measured the impact of the "intern learning curve" on patient
      length of stay (LOS). METHODS: We retrospectively analyzed one year of patient
      care data, generated by a comprehensive EDIS in a single, urban, university
      affiliated ED. Intern rotations began on the 23rd of each month and ended on the
      22nd of the next month. Interns received a 1.5-hour orientation to the EDIS prior
      to starting their rotation; none had prior experience using the electronic
      system. Mean LOS (+/- standard error of the mean) for all patients treated by an
      intern were calculated for each day of the month. Values for similar numerical
      days from each month were combined and averaged over the year resulting in 31
      discrete mean LOS values. The mean LOS on the first day of the intern rotation
      was compared with the mean LOS on the last day, using Student's t-test. RESULTS:
      During the study period 9,780 patients were cared for by interns; of these, 7,616
      (78%) were discharged from the ED and 2,164 (22%) were admitted to the hospital.
      The mean LOS for all patients on all days was 267 +/- 1.8 minutes. There was no
      difference between the LOS on the first day of the rotation (263+/-9 minutes) and
      the last day of the rotation (276 +/- 11 minutes, p > 0.9). In a multiple linear
      regression model, the day of the intern rotation was not associated with patient
      LOS, even after adjusting for the number of patients treated by interns and total
      ED census (beta = -0.34, p = 0.11). CONCLUSION: In this academic ED, where there
      is complete intern "turnover" every month, there was no discernible impact of the
      EDIS "learning curve" on patient LOS.

PMID- 21079704
TI  - Impact of resident physicians on emergency department throughput.
AB  - OBJECTIVE: Evaluate the impact of adding emergency medicine residents to a medium
      size urban hospital by comparing emergency department (ED) admission rate, total
      census, length of stay (LOS), and proportion of patients who left without being
      seen (LWBS). METHODS: Using the student t-test, the study compared commonly used
      ED metrics for a mid-sized urban hospital (annual census 43,000) for the four
      month period prior to (March-June 2006) and after (March-June 2007) residents
      began providing 24-hour coverage at the institution. RESULTS: There was no
      significant difference in the number of patients seen (NPS) in the two time
      periods, 14,471 and 14,699 patients respectively (p=0.507). Analysis of the NPS
      and LWBS was not statistically significant. The percentage of patients who LWBS
      decreased with the presence of residents (6.5% to 5.8%, p=0.531), and the overall
      ED LOS was similar (210 min vs. 219 min, p=0.56). Admission rate data
      demonstrated that residents had a similar admission rate (17.5% vs. 18%, p
      =0.332). CONCLUSION: ED flow depends on a number of variables with complex
      interactions. When comparing two similar time periods in consecutive years, the
      presence of resident physicians in the ED had no effect on the number of patients
      seen, patient LOS in the ED, or LWBS, thus supporting the conclusion that
      residents did not adversely affect the patient flow within the ED.

PMID- 21079705
TI  - Emergency department frequent user: pilot study of intensive case management to
      reduce visits and computed tomography.
AB  - OBJECTIVE: Emergency department (ED) frequent users account for a large number of
      annual ED visits and often receive radiological studies as a part of their
      evaluation. We report a pilot study of a case management program for ED frequent
      users to reduce ED usage and radiation exposure. METHODS: This observational
      retrospective study was performed at a community hospital ED. Between May 2006
      and April 2008, 96 patients were enrolled in a case management program and were
      followed through November 2008. The case management program consisted of a multi
      disciplinary team of physicians, nurses, social services and specialists in pain
      management and behavioral health. Patients were enrolled if they had five or more
      visits to the ED in the previous month, if a concern about a patient's ED use was
      raised by staff, or if they were identified by the California prescription
      monitoring program. Case management addressed specific patient issues and
      assisted with receiving consistent outpatient care. The number of ED visits per
      patient and the number of radiological studies at each of these visits was
      recorded. When reviewing data for analysis, we used the number of total images in
      all computed tomography (CT) scans during the given time period. RESULTS: In the
      six months prior to enrollment, patients averaged 2.3 ED visits per patient per
      month. In the six months after enrollment, patients averaged 0.6 ED visits per
      patient per month (P<0.0001), and all visits after enrollment up to November 2008
      averaged 0.4 visits per patient per month (P<0.0001). In the six months prior to
      enrollment, these patients averaged 25.6 CT images per patient per month. In the
      six months after enrollment, patients averaged 10.2 CT images per patient per
      month (P=0.001), and all CT images after enrollment up to November 2008 averaged
      8.1 CT images per patient per month (P=0.0001). This represents a decrease in ED
      use by 83% and a decrease in radiation exposure by 67%. CONCLUSION: Case
      management can significantly reduce ED use by frequent users, and can also
      decrease radiation exposure from diagnostic imaging.

PMID- 21079706
TI  - Eliminating amylase testing from the evaluation of pancreatitis in the emergency
      department.
AB  - BACKGROUND: Alterations in serum biomarkers have been used to evaluate for
      pancreatitis in the emergency department (ED). Studies have shown lipase to be as
      sensitive and more specific than amylase in diagnosing pancreatitis and that
      amylase plus lipase does not improve accuracy over lipase alone. OBJECTIVE: To
      determine effects of interventions to decrease ordering of amylase in the
      evaluation of pancreatitis. METHODS: We conducted a pre- and post-cohort study.
      The number of amylase and lipase tests ordered in the ED was recorded prior to
      intervention to establish a baseline. We introduced an educational intervention
      to order lipase without amylase. A second intervention involved removing amylase
      from bedside order entry forms. We introduced a third intervention that included
      deleting amylase from trauma order forms, and decoupling amylase and lipase in
      the computer ordering system. We recorded the number of lipase and amylase tests
      in weekly aggregates for comparison to the baseline. Data analysis using students
      t-test, standard deviation and p values are reported. RESULTS: Before
      interventions 93% of patients had both tests ordered. Educational interventions
      resulted in a decrease to 91% (p=0.06) of co-ordering. Further interventions
      decreased the percentage of patients evaluated with both tests to 14.3%. This
      translates into a decrease in patient charges of approximately $350,000 a year.
      CONCLUSION: Using simple structured interventions in the ED can reduce amylase
      ordering. Educational programming alone was not effective in significantly
      decreasing amylase ordering; however, education plus system-based interventions
      decreased amylase ordering.

PMID- 21079707
TI  - Use of health information technology to manage frequently presenting emergency
      department patients.
AB  - OBJECTIVE: To determine if the effective use of Health Information Technologies
      (HIT) and the Electronic Medical Record (EMR) affects emergency department (ED)
      usage in a complicated frequently presenting patient population. METHODS: A
      retrospective, observational study of 45 patients enrolled in our Frequent User
      Program called Community Resources for Emergency Department Overuse (CREDO)
      between June 2005 and July 2007. The study was conducted at an urban hospital
      with greater than 95,000 annual visits. Patients served as their own historical
      controls. In this pre-post study, the pre-intervention control period was
      determined by the number of months the patient had been enrolled in the program.
      The pre- and post-intervention time periods were the same for each patient but
      varied between patients. The intervention included using HIT to identify the most
      frequently presenting patients and creating individualized care plans for those
      patients. The care plans were made available through the EMR to all healthcare
      providers. Study variables in this study intervention included ED charges, lab
      studies ordered, number of ED visits, length of stay (LOS), and Total Emergency
      Department Contact Time (TEDCT), which is the product of the number of visits and
      the LOS. We analyzed these variables using paired T-tests. This study was
      approved by the institutional review board. RESULTS: Forty-five patients were
      enrolled, but nine were excluded for no post enrollment visits; thus, statistical
      analysis was conducted with n=36. The ED charges decreased by 24% from $64,721 to
      $49,208 (p=0.049). The number of lab studies ordered decreased by 28% from 1847
      to 1328 (p=0.04). The average number of ED visits/patient decreased by 25% from
      67.4 to 50.5 (p=0.046). The TEDCT decreased by 39% from 443.7 hours to 270.6
      hours (p=0.003). CONCLUSION: In this pre-post analysis of an intervention
      targeting ED frequent users, the use of HIT and the EMR to identify patients and
      store easily accessible care plans significantly reduced ED charges, labs
      ordered, number of ED visits, and the TEDCT.

PMID- 21079708
TI  - Sgarbossa Criteria are Highly Specific for Acute Myocardial Infarction with
      Pacemakers.
AB  - OBJECTIVE: In 1996 Sgarbossa reviewed 17 ventricular-paced electrocardiograms
      (ECGs) in acute myocardial infarction (AMI) for signs of ischemia. Several
      characteristics of the paced ECG were predictive of AMI. We sought to evaluate
      the criteria in ventricular-paced ECGs in an emergency department (ED) cohort.
      METHODS: Ventricular-paced ECGs in patients with elevated cardiac markers within
      12 hours of the ED ECG and a diagnosis of AMI were identified retrospectively
      (n=57) and compared with a control group of patients with ventricular-paced ECGs
      and negative cardiac markers (n=99). A blinded board certified cardiologist
      reviewed all ECGs for Sgarbossa criteria. This study was approved by the
      institutional review board. RESULTS: Application of Sgarbossa's criteria to the
      paced ECGs revealed the following: The sensitivity of "ST-segment elevation of 1
      mm concordant with the QRS complex" was unable to be calculated as no ECG fit
      this criterion;For "ST-segment depression of 1 mm in lead V1, V2, or V3," the
      sensitivity was 19% (95% CI 11-31%), specificity 81% (95% CI 72-87%), with a
      likelihood ratio of 1.06 (0.63-1.64);For "ST-segment elevation >5mm discordant
      with the QRS complex," the sensitivity was 10% (95% CI 5-21%), specificity 99%
      (95% CI 93-99%), with a likelihood ratio of 5.2 (1.3 - 21). CONCLUSION: In our
      review of ventricular-paced ECGs, the most clinically useful Sgarbossa criterion
      in identifying AMI was ST-segment elevation >5mm discordant with the QRS complex.
      This characteristic may prove helpful in identifying patients who may ultimately
      benefit from early aggressive AMI treatment strategies.

PMID- 21079709
TI  - Paget-schroetter syndrome: review of pathogenesis and treatment of effort
      thrombosis.
AB  - Effort thrombosis, or Paget-Schroetter Syndrome, refers to axillary-subclavian
      vein thrombosis associated with strenuous and repetitive activity of the upper
      extremities. Anatomical abnormalities at the thoracic outlet and repetitive
      trauma to the endothelium of the subclavian vein are key factors in its
      initiation and progression. The role of hereditary and acquired thrombophilias is
      unclear. The pathogenesis of effort thrombosis is thus distinct from other venous
      thromboembolic disorders. Doppler ultrasonography is the preferred initial test,
      while contrast venography remains the gold standard for diagnosis. Computed
      tomographic venography and magnetic resonance venography are comparable to
      conventional venography and are being increasingly used. Conservative management
      with anticoagulation alone is inadequate and leads to significant residual
      disability. An aggressive multimodal treatment strategy consisting of catheter
      directed thrombolysis, with or without early thoracic outlet decompression, is
      essential for optimizing outcomes. Despite excellent insights into its
      pathogenesis and advances in treatment, a significant number of patients with
      effort thrombosis continue to be treated suboptimally. Hence, there is an urgent
      need for increasing physician awareness about risk factors, etiology and the
      management of this unique and relatively infrequent disorder.

PMID- 21079710
TI  - Emergency Department Activation of Interventional Cardiology to Reduce Door-to
      Balloon Time.
AB  - BACKGROUND: Despite American College of Cardiology (ACC) and American Heart
      Association (AHA) guidelines, many hospitals have door-to-balloon times in excess
      of 90 minutes. Emergency Department (ED) activation of interventional cardiology
      has been described as an important strategy to reduce door-to-balloon time.
      However, prior studies on ED activation have been in suburban hospitals with door
      to-balloon times near the ACC/AHA targeted times. OBJECTIVE: To determine if ED
      activation of interventional cardiology could significantly improve reperfusion
      times and reach the ACC/AHA target of 90 minutes or less in a safety net
      hospital, a Level I trauma center and teaching hospital serving primarily
      uninsured and underinsured patient population with door-to-balloon times ranking
      in the lowest quartile of United States hospitals. METHODS: In this study, door
      to balloon times before and after implementation of ED activation were compared
      by retrospective chart review. RESULTS: Eighty patients were included in the
      study, 48 before and 32 after ED activation of interventional cardiology. Median
      door-to-balloon time decreased from 163.5 minutes before to 130 minutes after ED
      activation, a significant difference of 33.5 minutes (p=0.028). Door-to-balloon
      time on nights, weekends and holidays decreased from a median of 165.5 minutes to
      130 minutes, a reduction of 35.5 minutes, which also reached statistical
      significance (p=0.029). CONCLUSION: ED activation of interventional cardiology
      produced a statistically significant reduction in door-to-balloon time. However,
      the reduction was not enough to achieve a door-to-balloon time of less than 90
      minutes. Safety net hospitals with door-to-balloon times in the lowest quartile
      nationally may require multiple strategies to achieve targeted myocardial
      reperfusion times.

PMID- 21079711
TI  - Therapeutic hypothermia protocol in a community emergency department.
AB  - OBJECTIVES: Therapeutic hypothermia (TH) has been shown to improve survival and
      neurological outcome in patients resuscitated after out of hospital cardiac
      arrest (OHCA) from ventricular fibrillation/ventricular tachycardia (VF/VT). We
      evaluated the effects of using a TH protocol in a large community hospital
      emergency department (ED) for all patients with neurological impairment after
      resuscitated OHCA regardless of presenting rhythm. We hypothesized improved
      mortality and neurological outcomes without increased complication rates.
      METHODS: Our TH protocol entails cooling to 33 degrees C for 24 hours with an
      endovascular catheter. We studied patients treated with this protocol from
      November 2006 to November 2008. All non-pregnant, unresponsive adult patients
      resuscitated from any initial rhythm were included. Exclusion criteria were
      initial hypotension or temperature less than 30 degrees C, trauma, primary
      intracranial event, and coagulopathy. Control patients treated during the 12
      months before the institution of our TH protocol met the same inclusion and
      exclusion criteria. We recorded survival to hospital discharge, neurological
      status at discharge, and rates of bleeding, sepsis, pneumonia, renal failure, and
      dysrhythmias in the first 72 hours of treatment. RESULTS: Mortality rates were
      71.1% (95% CI, 56-86%) for 38 patients treated with TH and 72.3% (95% CI 59-86%)
      for 47 controls. In the TH group, 8% of patients (95% CI, 0-17%) had a good
      neurological outcome on discharge, compared to 0 (95% CI 0-8%) in the control
      group. In 17 patients with VF/VT treated with TH, mortality was 47% (95% CI 21
      74%) and 18% (95% CI 0-38%) had good neurological outcome; in 9 control patients
      with VF/VT, mortality was 67% (95% CI 28-100%), and 0% (95% CI 0-30%) had good
      neurological outcome. The groups were well-matched with respect to sex and age.
      Complication rates were similar or favored the TH group. CONCLUSION: Instituting
      a TH protocol for OHCA patients with any presenting rhythm appears safe in a
      community hospital ED. A trend towards improved neurological outcome in TH
      patients was seen, but did not reach significance. Patients with VF appeared to
      derive more benefit from TH than patients with other rhythms.

PMID- 21079712
TI  - Systemic Inflammatory Response Syndrome Predicts Mortality in Acute Coronary
      Syndrome without Congestive Heart Failure.
AB  - INTRODUCTION: High levels of inflammatory biochemical markers are associated with
      an increased risk among patients with acute coronary syndrome (ACS). The
      objective of the current study was to evaluate the prognostic significance of the
      systemic inflammatory response syndrome (SIRS) among ACS patients with no
      clinical or radiological evidence of congestive heart failure (CHF). METHODS:
      Consecutive patients with ACS and no clinical or radiological evidence of CHF in
      the emergency department (ED) were included in the study. The endpoint was
      hospital mortality. Categorical variables were compared by calculating
      proportions with 95% confidence intervals (CIs) and by using the Fisher Exact
      test. Continuous variables were compared by using the Wilcoxon Rank Sum test. The
      association of the variables with hospital mortality was assessed by using the
      logistic regression analysis. RESULTS: The study included 196 patients (60 years;
      female 32.6 %). Six patients (3.1 %) died in hospital and 22 patients (11.2 %)
      had SIRS on admission to the ED. The following variables were predictors of
      hospital mortality: age with an odds ratio (OR) of 1.1 (95% CI, 1-1.2) for each
      one additional year (p <0.01), systolic arterial pressure with an OR 0.9 (95% CI,
      0.9-1), diastolic arterial pressure with an OR 0.9 (95% CI, 0.8-1) for each one
      additional mmHg (p < 0.01), respiratory rate with an OR 1.5 (95% CI, 1.2-1.9) for
      each one additional breath per minute (p < 0.01), and SIRS with an OR 9 (95% CI,
      1.7-47.8) (p 0.02). Because of the small number of events, it was not possible to
      assess the independence of these risk factors. CONCLUSION: SIRS was a marker of
      increased risk of hospital mortality among patients with ACS and no clinical or
      radiological evidence of CHF.

PMID- 21079713
TI  - Echocardiography to supplement stress electrocardiography in emergency department
      chest pain patients.
AB  - INTRODUCTION: Chest pain (CP) patients in the Emergency Department (ED) present a
      diagnostic dilemma, with a low prevalence of coronary disease but grave
      consequences with misdiagnosis. A common diagnostic strategy involves ED cardiac
      monitoring while excluding myocardial necrosis, followed by stress testing. We
      sought to describe the use of stress echocardiography (echo) at our institution,
      to identify cardiac pathology compared with stress electrocardiography (ECG)
      alone. METHODS: Retrospective cohort study of 57 urban ED Chest Pain Unit (CPU)
      patients from 2002-2005 with stress testing suggesting ischemia. Our main
      descriptive outcome was proportion and type of discordant findings between stress
      ECG testing and stress echo. The secondary outcome was whether stress echo
      results appeared to change management. RESULTS: Thirty-four of 57 patients
      [59.7%, 95% confidence interval (CI) 46.9-72.4%] had stress echo results
      discordant with stress ECG results. The most common discordance was an abnormal
      stress ECG with a normal stress echo (n=17/57, 29.8%, CI 17.9-41.7%), followed by
      normal stress ECG but with reversible regional wall-motion abnormality on stress
      echo (n = 10/57, 17.5%, CI 7.7-27.4%). The remaining seven patients (12.3%, CI
      3.8-20.8%) had non-diagnostic stress ECG due to sub-maximal effort. Stress echo
      showed reversible wall-motion abnormality in two, and five were normal. Twenty
      five of the 34 patients (73.5%, CI 56.8-85.4%) with discordant results had a
      different diagnostic strategy than predicted from their stress ECG alone.
      CONCLUSION: The addition of echo to stress ECG testing in ED CPU patients altered
      diagnosis in 34/57 (59.7%, CI 46.9-72.4%) patients, and appeared to change
      management in 25/57 (43.9%, CI 31.8-57.6%) patients.

PMID- 21079714
TI  - Coronary disease in emergency department chest pain patients with recent negative
      stress testing.
AB  - BACKGROUND: Cardiac stress tests for diagnosis of coronary artery disease (CAD)
      are incompletely sensitive and specific. OBJECTIVE: We examined the frequency of
      significant CAD in patients presenting to the emergency department (ED) with
      chest pain who have had a recent negative or inconclusive (<85% of predicted
      maximum heart rate) cardiac stress test. METHODS: This was a retrospective chart
      review of patients identified from ED and cardiology registries at the study
      hospital. We included patients presenting to the ED with a chief complaint of
      chest pain, with a negative cardiac stress test in the past three years as the
      last cardiac test, and hospital admission. One-hundred sixty-four patients met
      the inclusion criteria. Their admission was reviewed for diagnosis of CAD by
      positive serum troponin, percutaneous coronary intervention, or positive stress
      test while an inpatient. RESULTS: Of 164 patients, 122(74.4%, 95% CI 67.7, 81.1)
      had a negative stress test prior to the index admission, while 42 (25.6%, 95% CI
      18.9, 32.3) had otherwise normal but inconclusive stress tests. Thirty-four
      (20.7%, 95% CI 14.4,27.0) of the included patients were determined to have CAD.
      Twenty-five of the 122 patients (20.5%, 95% CI 13.3, 27.7) had negative pre
      admission stress tests and nine of 42 patients (21.4%, 95% CI 9.0, 33.8) had
      inclusive stress tests of CAD. A statistical comparison between these two
      proportions showed no significant difference (p = .973). CONCLUSION: Due to
      inadequate sensitivity, negative non-invasive cardiac stress tests should not be
      used to rule out CAD. Patients with negative stress tests are just as likely to
      have CAD as patients with inconclusive stress tests.

PMID- 21079715
TI  - Idiopathic ventricular tachycardia: belhassen type.

PMID- 21079716
TI  - Intestinal angioedema misdiagnosed as recurrent episodes of gastroenteritis.
AB  - Emergency physicians (EP) frequently encounter angioedema involving the lips and
      tongue. However, angioedema from Angiotensin Converting Enzyme inhibitors or
      hereditary angioedema (HAE) can present with gastrointestinal symptoms due to
      bowel wall involvement. EPs should begin to consider this clinical entity as a
      potential cause for abdominal pain and associated gastrointestinal symptoms given
      the common use of medications that can precipitate angioedema. We report a case
      of a 34-year-old woman who presented with abdominal cramping, vomiting and
      diarrhea due to an acute exacerbation of HAE.

PMID- 21079717
TI  - Massive empyema.

PMID- 21079718
TI  - Acute stroke from air embolism after leg sclerotherapy.

PMID- 21079719
TI  - Orbital cellulitis and abscess.

PMID- 21079720
TI  - Frail patient with abdominal pain.
AB  - Volvulus is a frequent condition in patients presenting in the emergency
      department (ED) with abdominal pain. While cecal volvulus occurs more often in
      young patients, sigmoid volvulus is more common in elderly patients.

PMID- 21079721
TI  - Nausea and vomiting after surgery under general anesthesia: an evidence-based
      review concerning risk assessment, prevention, and treatment.
AB  - BACKGROUND: The German-language recommendations for the management of
      postoperative nausea and vomiting (PONV) have been revised by an expert
      committee. Major aspects of this revision are presented here in the form of an
      evidence-based review article. METHODS: The literature was systematically
      reviewed with the goal of revising the existing recommendations. New evidence
      based recommendations for the management of PONV were developed, approved by
      consensus, and graded according to the scheme of the Scottish Intercollegiate
      Guidelines Network (SIGN). RESULTS: The relevant risk factors for PONV include
      female sex, nonsmoker status, prior history of PONV, motion sickness, use of
      opioids during and after surgery, use of inhalational anesthetics and nitrous
      oxide, and the duration of anesthesia. PONV scoring systems provide a rough
      assessment of risk that can serve as the basis for a risk-adapted approach. Risk
      adapted prophylaxis, however, has not been shown to provide any greater benefit
      than fixed (combination) prophylaxis, and PONV risk scores have inherent
      limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two
      approaches to manage PONV is chosen, high-risk patients must be given multimodal
      prophylaxis, involving both the avoidance of known risk factors and the
      application of multiple validated and effective antiemetic interventions. PONV
      should be treated as soon as it arises, to minimize patient discomfort, the risk
      of medical complications, and the costs involved. CONCLUSION: PONV lowers patient
      satisfaction but is treatable. The effective, evidence-based measures of
      preventing and treating it should be implemented in routine practice.

PMID- 21079722
TI  - The pre-participation examination for leisure time physical activity: general
      medical and cardiological issues.
AB  - BACKGROUND: There is current debate on the appropriate type and extent of medical
      testing for amateur and hobby athletes before they engage in sports. In
      particular, views diverge on the value of an ECG at rest. METHODS: We selectively
      searched the Medline and Embase databases for relevant publications that appeared
      from 1990 to 2008. The most pertinent ones are discussed here along with current
      reviews and guidelines that give recommendations on pre-participation testing for
      amateur athletes. RESULTS: History-taking and physical examination are standard
      around the world. The American guidelines on pre-participation examination do not
      recommend an ECG at rest, yet the guidelines for most European countries
      explicitly recommend it. No prospective cohort studies have been performed to
      date that might provide high-grade evidence (class and level) to support this
      practice. We discuss the pros and cons of an ECG at rest and also present the
      guideline recommendations on exercise-ECG testing for amateur athletes over age
      40. CONCLUSION: In accordance with the current European recommendations, and in
      consideration of the risks of athletic activity, we recommend that all persons
      participating in sports should undergo a pre-participation examination that
      includes an ECG at rest. Although primary-prevention campaigns advise physically
      inactive persons to get regular exercise, prospective studies are still lacking
      as a basis for recommendations in this group.

PMID- 21079723
TI  - Advantages in vascular tumors.

PMID- 21079724
TI  - Parental Family Experiences, the Timing of First Sex, and Contraception.
AB  - By investigating the intergenerational consequences of multiple aspects of family
      experiences across the life course this paper advances what we know about the
      forces shaping children's initiation of sexual and contraceptive behaviors. Our
      aim is to advance the scientific understanding of early sexual experiences by
      explicitly considering contraceptive use and by differentiating between the
      consequences of parental family experiences during childhood and those during
      adolescence and young adulthood. Thanks to unique, highly detailed data measuring
      parental family experiences throughout the life course and sexual dynamics early
      in life it is possible to provide detailed empirical estimates of the
      relationship between parental family experiences and contraceptive use at first
      sex-a relationship about which we know relatively little. Findings reveal (1)
      significant simultaneous consequences of many different dimensions of parental
      family experiences for the timing of first sex and the likelihood of using
      contraception at first sex, but the specific dimensions of family important for
      the specific behavior vary across racial groups; and (2) that parental family
      experiences influence the timing of sex and contraceptive use differently.

PMID- 21079725
TI  - Three-dimensional localization precision of the double-helix point spread
      function versus astigmatism and biplane.
AB  - Wide-field microscopy with a double-helix point spread function (DH-PSF) provides
      three-dimensional (3D) position information beyond the optical diffraction limit.
      We compare the theoretical localization precision for an unbiased estimator of
      the DH-PSF to that for 3D localization by astigmatic and biplane imaging using
      Fisher information analysis including pixelation and varying levels of
      background. The DH-PSF results in almost constant localization precision in all
      three dimensions for a 2 MUm thick depth of field while astigmatism and biplane
      improve the axial localization precision over smaller axial ranges. For high
      signal-to-background ratio, the DH-PSF on average achieves better localization
      precision.

PMID- 21079726
TI  - Picosecond absorption relaxation measured with nanosecond laser photoacoustics.
AB  - Picosecond absorption relaxation-central to many disciplines-is typically
      measured by ultrafast (femtosecond or picosecond) pump-probe techniques, which
      however are restricted to optically thin and weakly scattering materials or
      require artificial sample preparation. Here, we developed a reflection-mode
      relaxation photoacoustic microscope based on a nanosecond laser and measured
      picosecond absorption relaxation times. The relaxation times of oxygenated and
      deoxygenated hemoglobin molecules, both possessing extremely low fluorescence
      quantum yields, were measured at 576 nm. The added advantages in dispersion
      susceptibility, laser-wavelength availability, reflection sensing, and expense
      foster the study of natural-including strongly scattering and nonfluorescent
      materials.

PMID- 21079727
TI  - First evidence for adoption in California sea lions.
AB  - Demographic parameters such as birth and death rates determine the persistence of
      populations. Understanding the mechanisms that influence these rates is essential
      to developing effective management strategies. Alloparental behavior, or the care
      of non-filial young, has been documented in many species and has been shown to
      influence offspring survival. However, the role of alloparental behavior in
      maintaining population viability has not been previously studied. Here, we
      provide the first evidence for adoption in California sea lions and show that
      adoption potentially works to maintain a high survival rate of young and may
      ultimately contribute to population persistence. Alloparental behavior should
      have a positive effect on the population growth rate when the sum of the effects
      on fitness for the alloparent and beneficiary is positive.

PMID- 21079728
TI  - Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8.
AB  - BACKGROUND: Thiadiazolidinones (TDZD) are small heterocyclic compounds first
      described as non-ATP competitive inhibitors of glycogen synthase kinase 3beta
      (GSK-3beta). In this study, we analyzed the effects of 4-benzyl-2-methyl-1,2,4
      thiadiazolidine-3,5-dione (TDZD-8), on murine GL261 cells growth in vitro and on
      the growth of established intracerebral murine gliomas in vivo.
      METHODOLOGY/PRINCIPAL FINDINGS: Our data show that TDZD-8 decreased proliferation
      and induced apoptosis of GL261 glioblastoma cells in vitro, delayed tumor growth
      in vivo, and augmented animal survival. These effects were associated with an
      early activation of extracellular signal-regulated kinase (ERK) pathway and
      increased expression of EGR-1 and p21 genes. Also, we observed a sustained
      activation of the ERK pathway, a concomitant phosphorylation and activation of
      ribosomal S6 kinase (p90RSK) and an inactivation of GSK-3beta by phosphorylation
      at Ser 9. Finally, treatment of glioblastoma stem cells with TDZD-8 resulted in
      an inhibition of proliferation and self-renewal of these cells.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that TDZD-8 uses a novel mechanism
      to target glioblastoma cells, and that malignant progenitor population could be a
      target of this compound.

PMID- 21079729
TI  - Smoking behaviour, involuntary smoking, attitudes towards smoke-free
      legislations, and tobacco control activities in the European Union.
AB  - BACKGROUND: The six most important cost-effective policies on tobacco control can
      be measured by the Tobacco Control Scale (TCS). The objective of our study was to
      describe the correlation between the TCS and smoking prevalence, self-reported
      exposure to secondhand smoke (SHS) and attitudes towards smoking restrictions in
      the 27 countries of the European Union (EU27). METHODS/PRINCIPAL FINDINGS:
      Ecologic study in the EU27. We used data from the TCS in 2007 and from the
      Eurobarometer on Tobacco Survey in 2008. We analysed the relations between the
      TCS and prevalence of smoking, self-reported exposure to SHS (home and work), and
      attitudes towards smoking bans by means of scatter plots and Spearman rank
      correlation coefficients (r(sp)). Among the EU27, smoking prevalence varied from
      22.6% in Slovenia to 42.1% in Greece. Austria was the country with the lowest TCS
      score (35) and the UK had the highest one (93). The correlation between smoking
      prevalence and TCS score was negative (r(sp) = -0.42, p = 0.03) and the
      correlation between TCS score and support to smoking bans in all workplaces was
      positive (r(sp) = 0.47, p = 0.01 in restaurants; r(sp) = 0.5, p = 0.008 in bars,
      pubs, and clubs; and r(sp) = 0.31, p = 0.12 in other indoor workplaces). The
      correlation between TCS score and self-reported exposure to SHS was negative, but
      statistically non-significant. CONCLUSIONS/SIGNIFICANCE: Countries with a higher
      score in the TCS have higher support towards smoking bans in all workplaces
      (including restaurants, bars, pubs and clubs, and other indoor workplaces). TCS
      scores were strongly, but not statistically, associated with a lower prevalence
      of smokers and a lower self-reported exposure to SHS.

PMID- 21079730
TI  - Comprehensive brain MRI segmentation in high risk preterm newborns.
AB  - Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and
      white matter signal abnormalities on MRI at term-equivalent age. MRI brain
      volumes could serve as biomarkers for evaluating the effects of neonatal
      intensive care and predicting neurodevelopmental outcomes. This requires
      detailed, accurate, and reliable brain MRI segmentation methods. We describe our
      efforts to develop such methods in high risk newborns using a combination of
      manual and automated segmentation tools. After intensive efforts to accurately
      define structural boundaries, two trained raters independently performed manual
      segmentation of nine subcortical structures using axial T2-weighted MRI scans
      from 20 randomly selected extremely preterm infants. All scans were re-segmented
      by both raters to assess reliability. High intra-rater reliability was achieved,
      as assessed by repeatability and intra-class correlation coefficients (ICC range:
      0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was
      slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach
      was developed that combined the parametric strengths of the Hidden Markov Random
      Field Expectation Maximization algorithm with non-parametric Parzen window
      classifier resulting in accurate white matter, gray matter, and CSF segmentation.
      Final manual correction of misclassification errors improved accuracy (similarity
      index range: 0.87 to 0.89) and facilitated objective quantification of white
      matter signal abnormalities. The semi-automated and manual methods were
      seamlessly integrated to generate full brain segmentation within two hours. This
      comprehensive approach can facilitate the evaluation of large cohorts to
      rigorously evaluate the utility of regional brain volumes as biomarkers of
      neonatal care and surrogate endpoints for neurodevelopmental outcomes.

PMID- 21079731
TI  - HMMSplicer: a tool for efficient and sensitive discovery of known and novel
      splice junctions in RNA-Seq data.
AB  - BACKGROUND: High-throughput sequencing of an organism's transcriptome, or RNA
      Seq, is a valuable and versatile new strategy for capturing snapshots of gene
      expression. However, transcriptome sequencing creates a new class of alignment
      problem: mapping short reads that span exon-exon junctions back to the reference
      genome, especially in the case where a splice junction is previously unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce HMMSplicer, an accurate and
      efficient algorithm for discovering canonical and non-canonical splice junctions
      in short read datasets. HMMSplicer identifies more splice junctions than
      currently available algorithms when tested on publicly available A. thaliana, P.
      falciparum, and H. sapiens datasets without a reduction in specificity.
      CONCLUSIONS/SIGNIFICANCE: HMMSplicer was found to perform especially well in
      compact genomes and on genes with low expression levels, alternative splice
      isoforms, or non-canonical splice junctions. Because HHMSplicer does not rely on
      pre-built gene models, the products of inexact splicing are also detected. For H.
      sapiens, we find 3.6% of 3' splice sites and 1.4% of 5' splice sites are inexact,
      typically differing by 3 bases in either direction. In addition, HMMSplicer
      provides a score for every predicted junction allowing the user to set a
      threshold to tune false positive rates depending on the needs of the experiment.
      HMMSplicer is implemented in Python. Code and documentation are freely available
      at http://derisilab.ucsf.edu/software/hmmsplicer.

PMID- 21079732
TI  - Heterogeneous pattern of retinal nerve fiber layer in multiple sclerosis. High
      resolution optical coherence tomography: potential and limitations.
AB  - BACKGROUND: Recently the reduction of the retinal nerve fibre layer (RNFL) was
      suggested to be associated with diffuse axonal damage in the whole CNS of
      multiple sclerosis (MS) patients. However, several points are still under
      discussion. (1) Is high resolution optical coherence tomography (OCT) required to
      detect the partly very subtle RNFL changes seen in MS patients? (2) Can a
      reduction of RNFL be detected in all MS patients, even in early disease courses
      and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along
      the visual pathways, which are both very common in MS, limit the predication of
      diffuse axonal degeneration in the whole CNS? The purpose of our study was to
      determine the baseline characteristics of clinical definite relapsing-remitting
      (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT
      technique. METHODOLOGY: Forty-two RRMS and 17 SPMS patients with and without
      history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls
      were analysed prospectively with the high resolution spectral-domain OCT device
      (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference
      images and eye tracking mode. Furthermore we performed tests for visual and
      contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color
      vision (Lanthony D-15), the Humphrey visual field and visual evoked potential
      testing (VEP). PRINCIPAL FINDINGS: All 4 groups (RRMS and SPMS with or without
      ON) showed significantly reduced RNFL globally, or at least in one of the
      peripapillary sectors compared to age-/sex-matched healthy controls. In patients
      with previous ON additional RNFL reduction was found. However, in many RRMS
      patients the RNFL was found within normal range. We found no correlation between
      RNFL reduction and disease duration (range 9-540 months). CONCLUSIONS: RNFL
      baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to
      markedly reduced levels).

PMID- 21079733
TI  - An essential difference between the flavonoids monoHER and quercetin in their
      interplay with the endogenous antioxidant network.
AB  - Antioxidants can scavenge highly reactive radicals. As a result the antioxidants
      are converted into oxidation products that might cause damage to vital cellular
      components. To prevent this damage, the human body possesses an intricate network
      of antioxidants that pass over the reactivity from one antioxidant to another in
      a controlled way. The aim of the present study was to investigate how the semi
      synthetic flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER), a potential
      protective agent against doxorubicin-induced cardiotoxicity, fits into this
      antioxidant network. This position was compared with that of the well-known
      flavonoid quercetin. The present study shows that the oxidation products of both
      monoHER and quercetin are reactive towards thiol groups of both GSH and proteins.
      However, in human blood plasma, oxidized quercetin easily reacts with protein
      thiols, whereas oxidized monoHER does not react with plasma protein thiols. Our
      results indicate that this can be explained by the presence of ascorbate in
      plasma; ascorbate is able to reduce oxidized monoHER to the parent compound
      monoHER before oxidized monoHER can react with thiols. This is a major difference
      with oxidized quercetin that preferentially reacts with thiols rather than
      ascorbate. The difference in selectivity between monoHER and quercetin originates
      from an intrinsic difference in the chemical nature of their oxidation products,
      which was corroborated by molecular quantum chemical calculations. These findings
      point towards an essential difference between structurally closely related
      flavonoids in their interplay with the endogenous antioxidant network. The
      advantage of monoHER is that it can safely channel the reactivity of radicals
      into the antioxidant network where the reactivity is completely neutralized.

PMID- 21079734
TI  - Semantic knowledge influences prewired hedonic responses to odors.
AB  - BACKGROUND: Odor hedonic perception relies on decoding the physicochemical
      properties of odorant molecules and can be influenced in humans by semantic
      knowledge. The effect of semantic knowledge on such prewired hedonic processing
      over the life span has remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: The
      present study measured hedonic response to odors in different age groups
      (children, teenagers, young adults, and seniors) and found that children and
      seniors, two age groups characterized by either low level of (children) or weak
      access to (seniors) odor semantic knowledge, processed odor hedonics more on the
      basis of their physicochemical properties. In contrast, in teenagers and young
      adults, who show better levels of semantic odor representation, the role of
      physicochemical properties was less marked. CONCLUSIONS/SIGNIFICANCE: These
      findings demonstrate for the first time that the biological determinants that
      make an odor pleasant or unpleasant are more powerful at either end of the life
      span.

PMID- 21079736
TI  - Distinct signature of altered homeostasis in aging rod photoreceptors:
      implications for retinal diseases.
AB  - BACKGROUND: Advanced age contributes to clinical manifestations of many
      retinopathies and represents a major risk factor for age-related macular
      degeneration, a leading cause of visual impairment and blindness in the elderly.
      Rod photoreceptors are especially vulnerable to genetic defects and changes in
      microenvironment, and are among the first neurons to die in normal aging and in
      many retinal degenerative diseases. The molecular mechanisms underlying rod
      photoreceptor vulnerability and potential biomarkers of the aging process in this
      highly specialized cell type are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To
      discover aging-associated adaptations that may influence rod function, we have
      generated gene expression profiles of purified rod photoreceptors from mouse
      retina at young adult to early stages of aging (1.5, 5, and 12 month old mice).
      We identified 375 genes that showed differential expression in rods from 5 and 12
      month old mouse retina compared to that of 1.5 month old retina. Quantitative RT
      PCR experiments validated expression change for a majority of the 25 genes that
      were examined. Macroanalysis of differentially expressed genes using gene class
      testing and protein interaction networks revealed overrepresentation of cellular
      pathways that are potentially photoreceptor-specific (angiogenesis and
      lipid/retinoid metabolism), in addition to age-related pathways previously
      described in several tissue types (oxidative phosphorylation, stress and immune
      response). CONCLUSIONS/SIGNIFICANCE: Our study suggests a progressive shift in
      cellular homeostasis that may underlie aging-associated functional decline in rod
      photoreceptors and contribute to a more permissive state for pathological
      processes involved in retinal diseases.

PMID- 21079735
TI  - Static magnetic field exposure reproduces cellular effects of the Parkinson's
      disease drug candidate ZM241385.
AB  - BACKGROUND: This study was inspired by coalescing evidence that magnetic therapy
      may be a viable treatment option for certain diseases. This premise is based on
      the ability of moderate strength fields (i.e., 0.1 to 1 Tesla) to alter the
      biophysical properties of lipid bilayers and in turn modulate cellular signaling
      pathways. In particular, previous results from our laboratory (Wang et al., BMC
      Genomics, 10, 356 (2009)) established that moderate strength static magnetic
      field (SMF) exposure altered cellular endpoints associated with neuronal function
      and differentiation. Building on this background, the current paper investigated
      SMF by focusing on the adenosine A(2A) receptor (A(2A)R) in the PC12 rat adrenal
      pheochromocytoma cell line that displays metabolic features of Parkinson's
      disease (PD). METHODOLOGY AND PRINCIPAL FINDINGS: SMF reproduced several
      responses elicited by ZM241385, a selective A(2A)R antagonist, in PC12 cells
      including altered calcium flux, increased ATP levels, reduced cAMP levels,
      reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited
      proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant
      endpoints exacerbated by A(2A)R agonist CGS21680 in a manner similar to ZM241385;
      these include reduction of increased expression of A(2A)R, reversal of altered
      calcium efflux, dampening of increased adenosine production, reduction of
      enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition
      of neurite outgrowth. CONCLUSIONS AND SIGNIFICANCE: When measured against
      multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a
      PD drug candidate. Provided that the in vitro results presented in this paper
      apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat
      PD and potentially other neurological disorders.

PMID- 21079737
TI  - RhoA regulates peroxisome association to microtubules and the actin cytoskeleton.
AB  - The current view of peroxisome inheritance provides for the formation of new
      peroxisomes by both budding from the endoplasmic reticulum and autonomous
      division. Here we investigate peroxisome-cytoskeleton interactions and show by
      proteomics, biochemical and immunofluorescence analyses that actin, non-muscle
      myosin IIA (NMM IIA), RhoA, Rho kinase II (ROCKII) and Rab8 associate with
      peroxisomes. Our data provide evidence that (i) RhoA in its inactive state,
      maintained for example by C. botulinum toxin exoenzyme C3, dissociates from
      peroxisomes enabling microtubule-based peroxisomal movements and (ii) dominant
      active RhoA targets to peroxisomes, uncouples the organelles from microtubules
      and favors Rho kinase recruitment to peroxisomes. We suggest that ROCKII
      activates NMM IIA mediating local peroxisomal constrictions. Although our
      understanding of peroxisome-cytoskeleton interactions is still incomplete, a
      picture is emerging demonstrating alternate RhoA-dependent association of
      peroxisomes to the microtubular and actin cytoskeleton. Whereas association of
      peroxisomes to microtubules clearly serves bidirectional, long-range saltatory
      movements, peroxisome-acto-myosin interactions may support biogenetic functions
      balancing peroxisome size, shape, number, and clustering.

PMID- 21079738
TI  - Anthrax toxin receptor drives protective antigen oligomerization and stabilizes
      the heptameric and octameric oligomer by a similar mechanism.
AB  - BACKGROUND: Anthrax toxin is comprised of protective antigen (PA), lethal factor
      (LF), and edema factor (EF). These proteins are individually nontoxic; however,
      when PA assembles with LF and EF, it produces lethal toxin and edema toxin,
      respectively. Assembly occurs either on cell surfaces or in plasma. In each
      milieu, PA assembles into a mixture of heptameric and octameric complexes that
      bind LF and EF. While octameric PA is the predominant form identified in plasma
      under physiological conditions (pH 7.4, 37 degrees C), heptameric PA is more
      prevalent on cell surfaces. The difference between these two environments is that
      the anthrax toxin receptor (ANTXR) binds to PA on cell surfaces. It is known that
      the extracellular ANTXR domain serves to stabilize toxin complexes containing the
      PA heptamer by preventing premature PA channel formation--a process that
      inactivates the toxin. The role of ANTXR in PA oligomerization and in the
      stabilization of toxin complexes containing octameric PA are not understood.
      METHODOLOGY: Using a fluorescence assembly assay, we show that the extracellular
      ANTXR domain drives PA oligomerization. Moreover, a dimeric ANTXR construct
      increases the extent of and accelerates the rate of PA assembly relative to a
      monomeric ANTXR construct. Mass spectrometry analysis shows that heptameric and
      octameric PA oligomers bind a full stoichiometric complement of ANTXR domains.
      Electron microscopy and circular dichroism studies reveal that the two different
      PA oligomers are equally stabilized by ANTXR interactions. CONCLUSIONS: We
      propose that PA oligomerization is driven by dimeric ANTXR complexes on cell
      surfaces. Through their interaction with the ANTXR, toxin complexes containing
      heptameric and octameric PA oligomers are similarly stabilized. Considering both
      the relative instability of the PA heptamer and extracellular assembly pathway
      identified in plasma, we propose a means to regulate the development of toxin
      gradients around sites of infection during anthrax pathogenesis.

PMID- 21079740
TI  - Irregular dynamics in up and down cortical states.
AB  - Complex coherent dynamics is present in a wide variety of neural systems. A
      typical example is the voltage transitions between up and down states observed in
      cortical areas in the brain. In this work, we study this phenomenon via a
      biologically motivated stochastic model of up and down transitions. The model is
      constituted by a simple bistable rate dynamics, where the synaptic current is
      modulated by short-term synaptic processes which introduce stochasticity and
      temporal correlations. A complete analysis of our model, both with mean-field
      approaches and numerical simulations, shows the appearance of complex transitions
      between high (up) and low (down) neural activity states, driven by the synaptic
      noise, with permanence times in the up state distributed according to a power
      law. We show that the experimentally observed large fluctuation in up and down
      permanence times can be explained as the result of sufficiently noisy dynamical
      synapses with sufficiently large recovery times. Static synapses cannot account
      for this behavior, nor can dynamical synapses in the absence of noise.

PMID- 21079739
TI  - Dioxin toxicity in vivo results from an increase in the dioxin-independent
      transcriptional activity of the aryl hydrocarbon receptor.
AB  - The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the
      toxicity of dioxins--widespread and persistent pollutants whose toxic effects
      include tumor promotion, teratogenesis, wasting syndrome and chloracne.
      Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse
      effects, some seemingly unrelated to dioxin. Thus the relationship between the
      toxic and dioxin-independent functions of Ahr is not clear, which hampers
      understanding and treatment of dioxin toxicity. Here we develop a Drosophila
      model to show that dioxin actually increases the in vivo dioxin-independent
      activity of Ahr. This hyperactivation resembles the effects caused by an increase
      in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and
      entails an increased transcriptional potency of Ahr, in addition to the
      previously described effect on nuclear translocation. Thus the two apparently
      different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact
      two different levels (hyperactivated and basal, respectively) of a single
      function.

PMID- 21079742
TI  - DNA suspension arrays: silencing discrete artifacts for high-sensitivity
      applications.
AB  - Detection of low frequency single nucleotide polymorphisms (SNPs) has important
      implications in early screening for tumorgenesis, genetic disorders and pathogen
      drug resistance. Nucleic acid arrays are a powerful tool for genome-scale SNP
      analysis, but detection of low-frequency SNPs in a mixed population on an array
      is problematic. We demonstrate a model assay for HIV-1 drug resistance mutations,
      wherein ligase discrimination products are collected on a suspension array. In
      developing this system, we discovered that signal from multiple polymorphisms was
      obscured by two discrete hybridization artifacts. Specifically: 1) tethering of
      unligated probes on the template DNA elicited false signal and 2) unpredictable
      probe secondary structures impaired probe capture and suppressed legitimate
      signal from the array. Two sets of oligonucleotides were used to disrupt these
      structures; one to displace unligated reporter labels from the bead-bound species
      and another to occupy sequences which interfered with array hybridization. This
      artifact silencing system resulted in a mean 21-fold increased sensitivity for 29
      minority variants of 17 codons in our model assay for mutations most commonly
      associated with HIV-1 drug resistance. Furthermore, since the artifacts we
      characterized are not unique to our system, their specific inhibition might
      improve the quality of data from solid-state microarrays as well as from the
      growing number of multiple analyte suspension arrays relying on sequence-specific
      nucleic acid target capture.

PMID- 21079741
TI  - The cell cycle time of CD8+ T cells responding in vivo is controlled by the type
      of antigenic stimulus.
AB  - A hallmark of cells comprising the mammalian adaptive immune system is the
      requirement for these rare naive T (and B) lymphocytes directed to a specific
      microorganism to undergo proliferative expansion upon first encounter with this
      antigen. In the case of naive CD8(+) T cells the ability of these rare quiescent
      lymphocytes to rapidly activate and expand into effector T cells in numbers
      sufficient to control viral and certain bacterial infections can be essential for
      survival. In this report we examined the activation, cell cycle time and initial
      proliferative response of naive murine CD8(+) T cells responding in vivo to
      Influenza and Vaccinia virus infection or vaccination with viral antigens.
      Remarkably, we observed that CD8(+) T cells could divide and proliferate with an
      initial cell division time of as short as 2 hours. The initial cell cycle time of
      responding CD8(+) T cells is not fixed but is controlled by the antigenic
      stimulus provided by the APC in vivo. Initial cell cycle time influences the rate
      of T cell expansion and the numbers of effector T cells subsequently accumulating
      at the site of infection. The T cell cycle time varies with duration of the G(1)
      phase of the cell cycle. The duration of G(1) is inversely correlated with the
      phosphorylation state of the retinoblastoma (Rb) protein in the responding T
      cells. The implication of these findings for the development of adaptive immune
      responses and the regulation of cell cycle in higher eukaryotic cells is
      discussed.

PMID- 21079743
TI  - Interaction of Crohn's disease susceptibility genes in an Australian paediatric
      cohort.
AB  - Genetic susceptibility is an important contributor to the pathogenesis of Crohn's
      disease (CD). We investigated multiple CD susceptibility genes in an Australian
      paediatric onset CD cohort. Newly diagnosed paediatric onset CD patients (n = 72)
      and controls (n = 98) were genotyped for 34 single nucleotide polymorphisms
      (SNPs) in 18 genetic loci. Gene-gene interaction analysis, gene-disease phenotype
      analysis and genetic risk profiling were performed for all SNPs and all genes. Of
      the 34 SNPs analysed, four polymorphisms on three genes (NOD2, IL23R, and region
      3p21) were significantly associated with CD status (p<0.05). All three CD
      specific paediatric polymorphisms on PSMG1 and TNFRSF6B showed a trend of
      association with p<0.1. An additive gene-gene interaction involving TLR4, PSMG1,
      TNFRSF6B and IRGM was identified with CD. Genes involved in microbial processing
      (TLR4, PSMG1, NOD2) were significantly associated either at the individual level
      or in gene-gene interactive roles. Colonic disease was significantly associated
      with disease SNP rs7517847 (IL23R) (p<0.05) and colonic and ileal/colonic disease
      was significantly associated with disease SNP rs125221868 (IBD5) and SLC22A4 &
      SLC22A4/5 variants (p<0.05). We were able to demonstrate genetic association of
      several genes to CD in a paediatric onset cohort. Several of the observed
      associations have not been reported previously in association with paediatric CD
      patients. Our findings demonstrate that CD genetic susceptibility in paediatric
      patients presents as a complex interaction between numerous genes.

PMID- 21079744
TI  - Microarray analysis reveals distinct gene expression profiles among different
      tumor histology, stage and disease outcomes in endometrial adenocarcinoma.
AB  - BACKGROUND: Endometrial cancer is the most common gynecologic malignancy in
      developed countries and little is known about the underlying mechanism of stage
      and disease outcomes. The goal of this study was to identify differentially
      expressed genes (DEG) between late vs. early stage endometrioid adenocarcinoma
      (EAC) and uterine serous carcinoma (USC), as well as between disease outcomes in
      each of the two histological subtypes. METHODOLOGY/PRINCIPAL FINDING: Gene
      expression profiles of 20 cancer samples were analyzed (EAC = 10, USC = 10) using
      the human genome wide illumina bead microarrays. There was little overlap in the
      DEG sets between late vs. early stages in EAC and USC, and there was an
      insignificant overlap in DEG sets between good and poor prognosis in EAC and USC.
      Remarkably, there was no overlap between the stage-derived DEGs and the prognosis
      derived DEGs for each of the two histological subtypes. Further functional
      annotation of differentially expressed genes showed that the composition of
      enriched function terms were different among different DEG sets. Gene expression
      differences for selected genes of various stages and outcomes were confirmed by
      qRT-PCR with a high validation rate. CONCLUSION: This data, although preliminary,
      suggests that there might be involvement of distinct groups of genes in tumor
      progression (late vs. early stage) in each of the EAC and USC. It also suggests
      that these genes are different from those involved in tumor outcome (good vs.
      poor prognosis). These involved genes, once clinically verified, may be important
      for predicting tumor progression and tumor outcome.

PMID- 21079745
TI  - C. elegans mutant identification with a one-step whole-genome-sequencing and SNP
      mapping strategy.
AB  - Whole-genome sequencing (WGS) is becoming a fast and cost-effective method to
      pinpoint molecular lesions in mutagenized genetic model systems, such as
      Caenorhabditis elegans. As mutagenized strains contain a significant mutational
      load, it is often still necessary to map mutations to a chromosomal interval to
      elucidate which of the WGS-identified sequence variants is the phenotype-causing
      one. We describe here our experience in setting up and testing a simple strategy
      that incorporates a rapid SNP-based mapping step into the WGS procedure. In this
      strategy, a mutant retrieved from a genetic screen is crossed with a polymorphic
      C. elegans strain, individual F2 progeny from this cross is selected for the
      mutant phenotype, the progeny of these F2 animals are pooled and then whole
      genome-sequenced. The density of polymorphic SNP markers is decreased in the
      region of the phenotype-causing sequence variant and therefore enables its
      identification in the WGS data. As a proof of principle, we use this strategy to
      identify the molecular lesion in a mutant strain that produces an excess of
      dopaminergic neurons. We find that the molecular lesion resides in the Pax
      6/Eyeless ortholog vab-3. The strategy described here will further reduce the
      time between mutant isolation and identification of the molecular lesion.

PMID- 21079746
TI  - S-adenosyl-methionine and betaine improve early virological response in chronic
      hepatitis C patients with previous nonresponse.
AB  - BACKGROUND/AIMS: Treatment of chronic hepatitis C (CHC) with pegylated interferon
      alpha (pegIFNalpha) and ribavirin results in a sustained response in
      approximately half of patients. Viral interference with IFNalpha signal
      transduction through the Jak-STAT pathway might be an important factor underlying
      treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNalpha
      signaling in cultured cells that express hepatitis C virus (HCV) proteins, and
      enhance the inhibitory effect of IFNalpha on HCV replicons. We have performed a
      clinical study with the aim to evaluate efficacy and safety of the addition of
      SAMe and betaine to treatment of CHC with pegIFNalpha/ribavirin. METHODS: In this
      open-label pilot study, 29 patients with CHC who failed previous therapy with
      (peg)IFNalpha/ribavirin were treated with SAMe, betaine, pegIFNalpha2b and
      ribavirin. Treatment duration was 6 or 12 months, depending on genotype, and the
      protocol comprised a stopping rule at week 12 if early virological response (EVR)
      was not achieved. Virological and biochemical response and safety were assessed
      throughout the treatment. RESULTS: 29 patients were enrolled and treated
      according to the study protocol. 79% of the patients were infected with genotype
      1, 72% had advanced fibrosis, 76% had previously received pegIFNalpha/ribavirin,
      and only 14% achieved EVR to the previous treatment. When treated with the study
      medications, 17 patients (59%) showed an EVR, only 3 (10%) however achieved a
      sustained virological response (SVR). SAMe and betaine were found to be safe when
      used with pegIFNalpha/ribavirin. CONCLUSION: The addition of SAMe and betaine to
      pegIFNalpha/ribavirin improves early virological response in CHC. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00310336.

PMID- 21079747
TI  - The neural substrate of positive bias in spontaneous emotional processing.
AB  - Even in the presence of negative information, healthy human beings display an
      optimistic tendency when thinking of past success and future chances, giving a
      positive bias to everyday's cognition. The tendency to actively select positive
      thoughts suggests the existence of a mechanism to exclude negative content,
      raising the issue of its dependence on mechanisms like those of effortful
      control. Using perfusion imaging, we examined how brain activations differed
      according to whether participants were left to prefer positive thoughts
      spontaneously, or followed an explicit instruction to the same effect, finding a
      widespread dissociation of brain perfusion patterns. Under spontaneous processing
      of emotional material, recruitment of areas associated with effortful attention,
      such as the dorsolateral prefrontal cortex, was reduced relative to instructed
      avoidance of negative material (F(1,58) = 26.24, p = 0.047, corrected). Under
      spontaneous avoidance perfusion increments were observed in several areas that
      were deactivated by the task, including the perigenual medial prefrontal cortex.
      Furthermore, individual differences in executive capacity were not associated
      with positive bias. These findings suggest that spontaneous positive cognitive
      emotion regulation in health may result from processes that, while actively
      suppressing emotionally salient information, differ from those associated with
      effortful and directed control.

PMID- 21079749
TI  - Error-based analysis of optimal tuning functions explains phenomena observed in
      sensory neurons.
AB  - Biological systems display impressive capabilities in effectively responding to
      environmental signals in real time. There is increasing evidence that organisms
      may indeed be employing near optimal Bayesian calculations in their decision
      making. An intriguing question relates to the properties of optimal encoding
      methods, namely determining the properties of neural populations in sensory
      layers that optimize performance, subject to physiological constraints. Within an
      ecological theory of neural encoding/decoding, we show that optimal Bayesian
      performance requires neural adaptation which reflects environmental changes.
      Specifically, we predict that neuronal tuning functions possess an optimal width,
      which increases with prior uncertainty and environmental noise, and decreases
      with the decoding time window. Furthermore, even for static stimuli, we
      demonstrate that dynamic sensory tuning functions, acting at relatively short
      time scales, lead to improved performance. Interestingly, the narrowing of tuning
      functions as a function of time was recently observed in several biological
      systems. Such results set the stage for a functional theory which may explain the
      high reliability of sensory systems, and the utility of neuronal adaptation
      occurring at multiple time scales.

PMID- 21079751
TI  - A fast neural signature of motivated attention to consumer goods separates the
      sexes.
AB  - Emotional stimuli guide selective visual attention and receive enhanced
      processing. Previous event-related potential studies have identified an early
      (>120 ms) negative potential shift over occipito-temporal regions (early
      posterior negativity, EPN) presumed to indicate the facilitated processing of
      survival-relevant stimuli. The present study investigated whether this neural
      signature of motivated attention is also responsive to the intrinsic significance
      of man-made objects and consumer goods. To address this issue, we capitalized on
      gender differences towards specific man-made objects, shoes and motorcycles, for
      which the Statistical Yearbook 2005 of Germany's Federal Statistical Office
      (Statistisches Bundesamt, 2005) revealed pronounced differences in consumer
      behavior. In a passive viewing paradigm, male and female participants viewed
      pictures of motorcycles and shoes, while their magnetoencephalographic brain
      responses were measured. Source localization of the magnetic counterpart of the
      EPN (EPNm) revealed pronounced gender differences in picture processing.
      Specifically, between 130 and 180 ms, all female participants generated stronger
      activity in occipito-temporal regions when viewing shoes compared to motorcycles,
      while all men except one showed stronger activation for motorcycles than shoes.
      Thus, the EPNm allowed a sex-dimorphic classification of the processing of
      consumer goods. Self-report data confirmed gender differences in consumer
      behavior, which, however, were less distinct compared to the brain based measure.
      Considering the latency of the EPNm, the reflected automatic emotional network
      activity is most likely not yet affected by higher cognitive functions such as
      response strategies or social expectancy. Non-invasive functional neuroimaging
      measures of early brain activity may thus serve as objective measure for
      individual preferences towards consumer goods.

PMID- 21079750
TI  - Early Neural Markers of Implicit Attitudes: N170 Modulated by Intergroup and
      Evaluative Contexts in IAT.
AB  - The Implicit Association Test (IAT) is the most popular measure to evaluate
      implicit attitudes. Nevertheless, its neural correlates are not yet fully
      understood. We examined event related potentials (ERPs) in response to face- and
      word processing while indigenous and non-indigenous participants performed an IAT
      displaying faces (ingroup and outgroup members) and words (positive and negative
      valence) as targets of category judgments. The N170 component was modulated by
      valence of words and by ingroup/outgroup face categorization. Contextual effects
      (face-words implicitly associated in the task) had an influence on the N170
      amplitude modulation. On the one hand, in face categorization, right N170 showed
      differences according to the association between social categories of faces and
      affective valence of words. On the other, in word categorization, left N170
      presented a similar modulation when the task implied a negative-valence
      associated with ingroup faces. Only indigenous participants showed a significant
      IAT effect and N170 differences. Our results demonstrate an early ERP blending of
      stimuli processing with both intergroup and evaluative contexts, suggesting an
      integration of contextual information related to intergroup attitudes during the
      early stages of word and face processing. To our knowledge, this is the first
      report of early ERPs during an ethnicity IAT, opening a new branch of exchange
      between social neuroscience and social psychology of attitudes.

PMID- 21079752
TI  - Measuring neuronal branching patterns using model-based approach.
AB  - Neurons have complex branching systems which allow them to communicate with
      thousands of other neurons. Thus understanding neuronal geometry is clearly
      important for determining connectivity within the network and how this shapes
      neuronal function. One of the difficulties in uncovering relationships between
      neuronal shape and its function is the problem of quantifying complex neuronal
      geometry. Even by using multiple measures such as: dendritic length, distribution
      of segments, direction of branches, etc, a description of three dimensional
      neuronal embedding remains incomplete. To help alleviate this problem, here we
      propose a new measure, a shape diffusiveness index (SDI), to quantify spatial
      relations between branches at the local and global scale. It was shown that
      growth of neuronal trees can be modeled by using diffusion limited aggregation
      (DLA) process. By measuring "how easy" it is to reproduce the analyzed shape by
      using the DLA algorithm it can be measured how "diffusive" is that shape.
      Intuitively, "diffusiveness" measures how tree-like is a given shape. For example
      shapes like an oak tree will have high values of SDI. This measure is capturing
      an important feature of dendritic tree geometry, which is difficult to assess
      with other measures. This approach also presents a paradigm shift from well
      defined deterministic measures to model-based measures, which estimate how well a
      model with specific properties can account for features of analyzed shape.

PMID- 21079748
TI  - Vulnerability of mesostriatal dopaminergic neurons in Parkinson's disease.
AB  - The term vulnerability was first associated with the midbrain dopaminergic
      neurons 85 years ago, before they were identified as monoaminergic neurons, when
      Foix and Nicolesco (1925) reported the loss of neuromelanin containing neurons in
      the midbrain of patients with post-encephalitic Parkinson's disease (PD). A few
      years later, Hassler (1938) showed that degeneration is more intense in the
      ventral tier of the substantia nigra compacta than in its dorsal tier and the
      ventral tegmental area (VTA), outlining the concept of differential vulnerability
      of midbrain dopaminergic (DA-) neurons. Nowadays, we know that other neuronal
      groups degenerate in PD, but the massive loss of nigral DA-cells is its
      pathological hallmark, having a pivotal position in the pathophysiology of the
      disease as it is responsible for the motor symptoms. Data from humans as well as
      cellular and animal models indicate that DA-cell degeneration is a complex
      process, probably precipitated by the convergence of different risk factors,
      mediated by oxidative stress, and involving pathogenic factors arising within the
      DA-neuron (intrinsic factors), and from its environment and distant
      interconnected brain regions (extrinsic factors). In light of current data,
      intrinsic factors seem to be preferentially involved in the first steps of the
      degenerative process, and extrinsic factors in its progression. A controversial
      issue is the relative weight of the impairment of common cell functions, such as
      energy metabolism and proteostasis, and specific dopaminergic functions, such as
      pacemaking activity and DA handling, in the pathogenesis of DA-cell degeneration.
      Here we will review the current knowledge about the relevance of these factors at
      the beginning and during the progression of PD, and in the differential
      vulnerability of midbrain DA-cells.

PMID- 21079753
TI  - Usefulness of cardiac computed tomography in the diagnosis of prosthetic coronary
      artery graft with interposition procedure.
AB  - An 80-year-old Japanese man was admitted with orthopnea and pitting edema of both
      lower legs. We diagnosed congestive heart failure (CHF) on the basis of a chest X
      ray and an echocardiogram. An electrocardiogram showed a heart rate of 120
      beats/min with atrial fibrillation rhythm (Af). The patient developed aortic
      valve failure and destruction of the base of right coronary artery (RCA) due to
      infectious endocarditis at 71 years of age. The patient underwent aortic valve
      replacement and coronary artery bypass grafting with an interposed graft with
      polyester vascular graft to RCA. The patient recovered from CHF after the 6 days
      of treatment with diuretics and verapamil. We confirmed the patency of coronary
      arteries and bypass grafts using a 64-slice cardiac computed tomography scan (CT)
      and diagnosed CHF due to Af. Here we describe the estimation of the prosthetic
      coronary artery graft patency with the interposition procedure using 64-slice
      cardiac CT.

PMID- 21079754
TI  - Niacin or ezetimibe for patients with, or at risk of coronary heart disease.
AB  - Coronary heart disease treatment with HMG-CoA reductase inhibitors has been very
      successful. There is increasing interest in adding other lipid lowering therapy,
      primarily as additional therapy onto HMG-CoA reductase therapy. This paper will
      examine two of the more popular secondary agents, ezetimibe and niacin, and
      describe their research data and potential for usefulness in further reducing
      cardiovascular events.

PMID- 21079755
TI  - EvoPipes.net: Bioinformatic Tools for Ecological and Evolutionary Genomics.
AB  - Recent increases in the production of genomic data are yielding new opportunities
      and challenges for biologists. Among the chief problems posed by next-generation
      sequencing are assembly and analyses of these large data sets. Here we present an
      online server, http://EvoPipes.net, that provides access to a wide range of tools
      for bioinformatic analyses of genomic data oriented for ecological and
      evolutionary biologists. The EvoPipes.net server includes a basic tool kit for
      analyses of genomic data including a next-generation sequence cleaning pipeline
      (SnoWhite), scaffolded assembly software (SCARF), a reciprocal best-blast hit
      ortholog pipeline (RBH Orthologs), a pipeline for reference protein-based
      translation and identification of reading frame in transcriptome and genomic DNA
      (TransPipe), a pipeline to identify gene families and summarize the history of
      gene duplications (DupPipe), and a tool for developing SSRs or microsatellites
      from a transcriptome or genomic coding sequence collection (findSSR).
      EvoPipes.net also provides links to other software developed for evolutionary and
      ecological genomics, including chromEvol and NU-IN, as well as a forum for
      discussions of issues relating to genomic analyses and interpretation of results.
      Overall, these applications provide a basic bioinformatic tool kit that will
      enable ecologists and evolutionary biologists with relatively little experience
      and computational resources to take advantage of the opportunities provided by
      next-generation sequencing in their systems.

PMID- 21079756
TI  - Computational identification of anthocyanin-specific transcription factors using
      a rice microarray and maximum boundary range algorithm.
AB  - This study identifies 2,617 candidate genes related to anthocyanin biosynthesis
      in rice using microarray analysis and a newly developed maximum boundary range
      algorithm. Three seed developmental stages were examined in white cultivar and
      two black Dissociation insertion mutants. The resultant 235 transcription factor
      genes found to be associated with anthocyanin were classified into nine groups.
      It is compared the 235 genes by transcription factor analysis and 593 genes from
      among clusters of COGs related to anthocyanin functions. Total 32 genes were
      found to be expressed commonly. Among these, 9 unknown and hypothetical genes
      were revealed to be expressed at each developmental stage and were verified by RT
      PCR. These genes most likely play regulatory roles in either anthocyanin
      production or metabolism during flavonoid biosynthesis. While these genes require
      further validation, our results underline the potential usefulness of the newly
      developed algorithm.

PMID- 21079757
TI  - Impaired thymic selection and abnormal antigen-specific T cell responses in
      Foxn1(Delta/Delta) mutant mice.
AB  - BACKGROUND: Foxn1(Delta/Delta) mutant mice have a specific defect in thymic
      development, characterized by a block in TEC differentiation at an intermediate
      progenitor stage, and blocks in thymocyte development at both the DN1 and DP cell
      stages, resulting in the production of abnormally functioning T cells that
      develop from an atypical progenitor population. In the current study, we tested
      the effects of these defects on thymic selection. METHODOLOGY/PRINCIPAL FINDINGS:
      We used Foxn1(Delta/Delta); DO11 Tg and Foxn1(Delta/Delta); OT1 Tg mice as
      positive selection and Foxn1(Delta/Delta); MHCII I-E mice as negative selection
      models. We also used an in vivo system of antigen-specific reactivity to test the
      function of peripheral T cells. Our data show that the capacity for positive and
      negative selection of both CD4 and CD8 SP thymocytes was reduced in
      Foxn1(Delta/Delta) mutants compared to Foxn1(+/Delta) control mice. These defects
      were associated with reduction of both MHC Class I and Class II expression,
      although the resulting peripheral T cells have a broad TCR Vbeta repertoire. In
      this deficient thymic environment, immature CD4 and CD8 SP thymocytes emigrate
      from the thymus into the periphery. These T cells had an incompletely activated
      profile under stimulation of the TCR signal in vitro, and were either
      hypersensitive or hyporesponsive to antigen-specific stimulation in vivo. These
      cell-autonomous defects were compounded by the hypocellular peripheral
      environment caused by low thymic output. CONCLUSIONS/SIGNIFICANCE: These data
      show that a primary defect in the thymic microenvironment can cause both direct
      defects in selection which can in turn cause indirect effects on the periphery,
      exacerbating functional defects in T cells.

PMID- 21079758
TI  - Nonnative interactions in coupled folding and binding processes of intrinsically
      disordered proteins.
AB  - Proteins function by interacting with other molecules, where both native and
      nonnative interactions play important roles. Native interactions contribute to
      the stability and specificity of a complex, whereas nonnative interactions mainly
      perturb the binding kinetics. For intrinsically disordered proteins (IDPs), which
      do not adopt rigid structures when being free in solution, the role of nonnative
      interactions may be more prominent in binding processes due to their high
      flexibilities. In this work, we investigated the effect of nonnative hydrophobic
      interactions on the coupled folding and binding processes of IDPs and its
      interplay with chain flexibility by conducting molecular dynamics simulations.
      Our results showed that the free-energy profiles became rugged, and intermediate
      states occurred when nonnative hydrophobic interactions were introduced. The
      binding rate was initially accelerated and subsequently dramatically decreased as
      the strength of the nonnative hydrophobic interactions increased. Both
      thermodynamic and kinetic analysis showed that disordered systems were more
      readily affected by nonnative interactions than ordered systems. Furthermore, it
      was demonstrated that the kinetic advantage of IDPs ("fly-casting" mechanism) was
      enhanced by nonnative hydrophobic interactions. The relationship between chain
      flexibility and protein aggregation is also discussed.

PMID- 21079759
TI  - Platelet-activating factor receptor plays a role in lung injury and death caused
      by Influenza A in mice.
AB  - Influenza A virus causes annual epidemics which affect millions of people
      worldwide. A recent Influenza pandemic brought new awareness over the health
      impact of the disease. It is thought that a severe inflammatory response against
      the virus contributes to disease severity and death. Therefore, modulating the
      effects of inflammatory mediators may represent a new therapy against Influenza
      infection. Platelet activating factor (PAF) receptor (PAFR) deficient mice were
      used to evaluate the role of the gene in a model of experimental infection with
      Influenza A/WSN/33 H1N1 or a reassortant Influenza A H3N1 subtype. The following
      parameters were evaluated: lethality, cell recruitment to the airways, lung
      pathology, viral titers and cytokine levels in lungs. The PAFR antagonist PCA4248
      was also used after the onset of flu symptoms. Absence or antagonism of PAFR
      caused significant protection against flu-associated lethality and lung injury.
      Protection was correlated with decreased neutrophil recruitment, lung edema,
      vascular permeability and injury. There was no increase of viral load and greater
      recruitment of NK1.1(+) cells. Antibody responses were similar in WT and PAFR
      deficient mice and animals were protected from re-infection. Influenza infection
      induces the enzyme that synthesizes PAF, lyso-PAF acetyltransferase, an effect
      linked to activation of TLR7/8. Therefore, it is suggested that PAFR is a disease
      associated gene and plays an important role in driving neutrophil influx and lung
      damage after infection of mice with two subtypes of Influenza A. Further studies
      should investigate whether targeting PAFR may be useful to reduce lung pathology
      associated with Influenza A virus infection in humans.

PMID- 21079760
TI  - Large-scale spatial distribution patterns of echinoderms in nearshore rocky
      habitats.
AB  - This study examined echinoderm assemblages from nearshore rocky habitats for
      large-scale distribution patterns with specific emphasis on identifying
      latitudinal trends and large regional hotspots. Echinoderms were sampled from 76
      globally-distributed sites within 12 ecoregions, following the standardized
      sampling protocol of the Census of Marine Life NaGISA project
      (www.nagisa.coml.org). Sample-based species richness was overall low (<1-5
      species per site), with a total of 32 asteroid, 18 echinoid, 21 ophiuroid, and 15
      holothuroid species. Abundance and species richness in intertidal assemblages
      sampled with visual methods (organisms >2 cm in 1 m(2) quadrats) was highest in
      the Caribbean ecoregions and echinoids dominated these assemblages with an
      average of 5 ind m(-2). In contrast, intertidal echinoderm assemblages collected
      from clearings of 0.0625 m(2) quadrats had the highest abundance and richness in
      the Northeast Pacific ecoregions where asteroids and holothurians dominated with
      an average of 14 ind 0.0625 m(-2). Distinct latitudinal trends existed for
      abundance and richness in intertidal assemblages with declines from peaks at high
      northern latitudes. No latitudinal trends were found for subtidal echinoderm
      assemblages with either sampling technique. Latitudinal gradients appear to be
      superseded by regional diversity hotspots. In these hotspots echinoderm
      assemblages may be driven by local and regional processes, such as overall
      productivity and evolutionary history. We also tested a set of 14 environmental
      variables (six natural and eight anthropogenic) as potential drivers of
      echinoderm assemblages by ecoregions. The natural variables of salinity, sea
      surface temperature, chlorophyll a, and primary productivity were strongly
      correlated with echinoderm assemblages; the anthropogenic variables of inorganic
      pollution and nutrient contamination also contributed to correlations. Our
      results indicate that nearshore echinoderm assemblages appear to be shaped by a
      network of environmental and ecological processes, and by the differing responses
      of various echinoderm taxa, making generalizations about the patterns of
      nearshore rocky habitat echinoderm assemblages difficult.

PMID- 21079761
TI  - Applying Fishers' ecological knowledge to construct past and future lobster
      stocks in the Juan Fernandez Archipelago, Chile.
AB  - Over-exploited fisheries are a common feature of the modern world and a range of
      solutions including area closures (marine reserves; MRs), effort reduction, gear
      changes, ecosystem-based management, incentives and co-management have been
      suggested as techniques to rebuild over-fished populations. Historic accounts of
      lobster (Jasus frontalis) on the Chilean Juan Fernandez Archipelago indicate a
      high abundance at all depths (intertidal to approximately 165 m), but presently
      lobsters are found almost exclusively in deeper regions of their natural
      distribution. Fishers' ecological knowledge (FEK) tells a story of serial
      depletion in lobster abundance at fishing grounds located closest to the fishing
      port with an associated decline in catch per unit effort (CPUE) throughout recent
      history. We have re-constructed baselines of lobster biomass throughout human
      history on the archipelago using historic data, the fishery catch record and FEK
      to permit examination of the potential effects of MRs, effort reduction and co
      management (stewardship of catch) to restore stocks. We employed a bioeconomic
      model using FEK, fishery catch and effort data, underwater survey information,
      predicted population growth and response to MR protection (no-take) to explore
      different management strategies and their trade-offs to restore stocks and
      improve catches. Our findings indicate that increased stewardship of catch
      coupled with 30% area closure (MR) provides the best option to reconstruct
      historic baselines. Based on model predictions, continued exploitation under the
      current management scheme is highly influenced by annual fluctuations and
      unsustainable. We propose a community-based co-management program to implement a
      MR in order to rebuild the lobster population while also providing conservation
      protection for marine species endemic to the Archipelago.

PMID- 21079762
TI  - Phase I study of safety and immunogenicity of an Escherichia coli-derived
      recombinant protective antigen (rPA) vaccine to prevent anthrax in adults.
AB  - BACKGROUND: The fatal disease caused by Bacillus anthracis is preventable with a
      prophylactic vaccine. The currently available anthrax vaccine requires a lengthy
      immunization schedule, and simpler and more immunogenic options for protection
      against anthrax are a priority for development. In this report we describe a
      phase I clinical trial testing the safety and immunogenicity of an anthrax
      vaccine using recombinant Escherichia coli-derived, B. anthracis protective
      antigen (rPA). METHODOLOGY/PRINCIPAL FINDINGS: A total of 73 healthy adults ages
      18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either
      buffered saline placebo, or rPA formulated with or without 704 ug/ml
      Alhydrogel(r) adjuvant in increasing doses (5, 25, 50, 100 ug) of rPA.
      Participants were followed for one year and safety and immunologic data were
      assessed. Tenderness and warmth were the most common post-injection site
      reactions. No serious adverse events related to the vaccine were observed. The
      most robust humoral immune responses were observed in subjects receiving 50 ug of
      rPA formulated with Alhydrogel(r) with a geometric mean concentration of anti-rPA
      IgG antibodies of 283 ug/ml and a toxin neutralizing geometric 50% reciprocal
      geometric mean titer of 1061. The highest lymphoproliferative peak cellular
      response (median Lymphocyte Stimulation Index of 29) was observed in the group
      receiving 25 ug Alhydrogel(r)-formulated rPA. CONCLUSIONS/SIGNIFICANCE: The
      vaccine was safe, well tolerated and stimulated a robust humoral and cellular
      response after two doses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00057525.

PMID- 21079763
TI  - Redox regulation of the AMP-activated protein kinase.
AB  - Redox state is a critical determinant of cell function, and any major imbalances
      can cause severe damage or death. OBJECTIVES: The aim of this study is to
      determine if AMP-activated protein kinase (AMPK), a cellular energy sensor, is
      activated by oxidants generated by Berberine in endothelial cells (EC). METHODS:
      Bovine aortic endothelial cells (BAEC) were exposed to Berberine. AMPK activity
      and reactive oxygen species were monitored after the incubation. RESULTS: In
      BAEC, Berberine caused a dose- and time-dependent increase in the phosphorylation
      of AMPK at Thr172 and acetyl CoA carboxylase (ACC) at Ser79, a well characterized
      downstream target of AMPK. Concomitantly, Berberine increased peroxynitrite, a
      potent oxidant formed by simultaneous generation of superoxide and nitric oxide.
      Pre-incubation of BAEC with anti-oxidants markedly attenuated Berberine-enhanced
      phosphorylation of both AMPK and ACC. Consistently, adenoviral expression of
      superoxide dismutase and pretreatment of L-N(G)-Nitroarginine methyl ester (L
      NAME; a non-selective NOS inhibitor) blunted Berberine-induced phosphorylation of
      AMPK. Furthermore, mitochondria-targeted tempol (mito-tempol) pretreatment or
      expression of uncoupling protein attenuated AMPK activation caused by Berberine.
      Depletion of mitochondria abolished the effects of Berberine on AMPK in EC.
      Finally, Berberine significantly increased the phosphorylation of LKB1 at Ser307
      and gene silencing of LKB1 attenuated Berberine-enhanced AMPK Thr172
      phosphorylation in BAEC. CONCLUSION: Our results suggest that mitochondria
      derived superoxide anions and peroxynitrite are required for Berberine-induced
      AMPK activation in endothelial cells.

PMID- 21079764
TI  - MEG responses to the perception of global structure within glass patterns.
AB  - BACKGROUND: The perception of global form requires integration of local visual
      cues across space and is the foundation for object recognition. Here we used
      magnetoencephalography (MEG) to study the location and time course of neuronal
      activity associated with the perception of global structure from local image
      features. To minimize neuronal activity to low-level stimulus properties, such as
      luminance and contrast, the local image features were held constant during all
      phases of the MEG recording. This allowed us to assess the relative importance of
      striate (V1) versus extrastriate cortex in global form perception.
      METHODOLOGY/PRINCIPAL FINDINGS: Stimuli were horizontal, rotational and radial
      Glass patterns. Glass patterns without coherent structure were viewed during the
      baseline period to ensure neuronal responses reflected perception of structure
      and not changes in local image features. The spatial distribution of task-related
      changes in source power was mapped using Synthetic Aperture Magnetometry (SAM),
      and the time course of activity within areas of maximal power change was
      determined by calculating time-frequency plots using a Hilbert transform. For six
      out of eight observers, passive viewing of global structure was associated with a
      reduction in 10-20 Hz cortical oscillatory power within extrastriate occipital
      cortex. The location of greatest power change was the same for each pattern type,
      being close to or within visual area V3a. No peaks of activity were observed in
      area V1. Time-frequency analyses indicated that neural activity was least for
      horizontal patterns. CONCLUSIONS: We conclude: (i) visual area V3a is involved in
      the analysis of global form; (ii) the neural signature for perception of
      structure, as assessed using MEG, is a reduction in 10-20 Hz oscillatory power;
      (iii) different neural processes may underlie the perception of horizontal as
      opposed to radial or rotational structure; and (iv) area V1 is not strongly
      activated by global form in Glass patterns.

PMID- 21079765
TI  - Proteomic analysis of the dysferlin protein complex unveils its importance for
      sarcolemmal maintenance and integrity.
AB  - Dysferlin is critical for repair of muscle membranes after damage. Mutations in
      dysferlin lead to a progressive muscular dystrophy. Recent studies suggest
      additional roles for dysferlin. We set out to study dysferlin's protein-protein
      interactions to obtain comprehensive knowledge of dysferlin functionalities in a
      myogenic context. We developed a robust and reproducible method to isolate
      dysferlin protein complexes from cells and tissue. We analyzed the composition of
      these complexes in cultured myoblasts, myotubes and skeletal muscle tissue by
      mass spectrometry and subsequently inferred potential protein functions through
      bioinformatics analyses. Our data confirm previously reported interactions and
      support a function for dysferlin as a vesicle trafficking protein. In addition
      novel potential functionalities were uncovered, including phagocytosis and focal
      adhesion. Our data reveal that the dysferlin protein complex has a dynamic
      composition as a function of myogenic differentiation. We provide additional
      experimental evidence and show dysferlin localization to, and interaction with
      the focal adhesion protein vinculin at the sarcolemma. Finally, our studies
      reveal evidence for cross-talk between dysferlin and its protein family member
      myoferlin. Together our analyses show that dysferlin is not only a membrane
      repair protein but also important for muscle membrane maintenance and integrity.

PMID- 21079767
TI  - Evaluating the cost-effectiveness of pre-exposure prophylaxis (PrEP) and its
      impact on HIV-1 transmission in South Africa.
AB  - BACKGROUND: Mathematical modelers have given little attention to the question of
      how pre-exposure prophylaxis (PrEP) may impact on a generalized national HIV
      epidemic and its cost-effectiveness, in the context of control strategies such as
      condom use promotion and expanding ART programs. METHODOLOGY/PRINCIPAL FINDINGS:
      We use an age- and gender-structured model of the generalized HIV epidemic in
      South Africa to investigate the potential impact of PrEP in averting new
      infections. The model utilizes age-structured mortality, fertility, partnership
      and condom use data to model the spread of HIV and the shift of peak prevalence
      to older age groups. The model shows that universal PrEP coverage would have to
      be impractically high to have a significant effect on incidence reduction while
      ART coverage expands. PrEP targeted to 15-35-year-old women would avert 10%-25%
      (resp. 13%-28%) of infections in this group and 5%-12% (resp. 7%-16%) of all
      infections in the period 2014-2025 if baseline incidence is 0.5% per year at 2025
      (resp. 0.8% per year at 2025). The cost would be $12,500-$20,000 per infection
      averted, depending on the level of ART coverage and baseline incidence. An
      optimistic scenario of 30%-60% PrEP coverage, efficacy of at least 90%, no
      behavior change among PrEP users and ART coverage less than three times its 2010
      levels is required to achieve this result. Targeting PrEP to 25-35-year-old women
      (at highest risk of infection) improves impact and cost-effectiveness marginally.
      Relatively low levels of condom substitution (e.g., 30%) do not nullify the
      efficacy of PrEP, but reduces cost-effectiveness by 35%-40%.
      CONCLUSIONS/SIGNIFICANCE: PrEP can avert as many as 30% of new infections in
      targeted age groups of women at highest risk of infection. The cost-effectiveness
      of PrEP relative to ART decreases rapidly as ART coverage increases beyond three
      times its coverage in 2010, after which the ART program would provide coverage to
      more than 65% of HIV(+) individuals. To have a high relative cost-effective
      impact on reducing infections in generalized epidemics, PrEP must utilize a
      window of opportunity until ART has been scaled up beyond this level.

PMID- 21079766
TI  - First investigation of the microbiology of the deepest layer of ocean crust.
AB  - The gabbroic layer comprises the majority of ocean crust. Opportunities to sample
      this expansive crustal environment are rare because of the technological demands
      of deep ocean drilling; thus, gabbroic microbial communities have not yet been
      studied. During the Integrated Ocean Drilling Program Expeditions 304 and 305,
      igneous rock samples were collected from 0.45-1391.01 meters below seafloor at
      Hole 1309D, located on the Atlantis Massif (30  degrees N, 42  degrees W).
      Microbial diversity in the rocks was analyzed by denaturing gradient gel
      electrophoresis and sequencing (Expedition 304), and terminal restriction
      fragment length polymorphism, cloning and sequencing, and functional gene
      microarray analysis (Expedition 305). The gabbroic microbial community was
      relatively depauperate, consisting of a low diversity of proteobacterial lineages
      closely related to Bacteria from hydrocarbon-dominated environments and to known
      hydrocarbon degraders, and there was little evidence of Archaea. Functional gene
      diversity in the gabbroic samples was analyzed with a microarray for metabolic
      genes ("GeoChip"), producing further evidence of genomic potential for
      hydrocarbon degradation--genes for aerobic methane and toluene oxidation. Genes
      coding for anaerobic respirations, such as nitrate reduction, sulfate reduction,
      and metal reduction, as well as genes for carbon fixation, nitrogen fixation, and
      ammonium-oxidation, were also present. Our results suggest that the gabbroic
      layer hosts a microbial community that can degrade hydrocarbons and fix carbon
      and nitrogen, and has the potential to employ a diversity of non-oxygen electron
      acceptors. This rare glimpse of the gabbroic ecosystem provides further support
      for the recent finding of hydrocarbons in deep ocean gabbro from Hole 1309D. It
      has been hypothesized that these hydrocarbons might originate abiotically from
      serpentinization reactions that are occurring deep in the Earth's crust, raising
      the possibility that the lithic microbial community reported here might utilize
      carbon sources produced independently of the surface biosphere.

PMID- 21079768
TI  - Biomechanical consequences of rapid evolution in the polar bear lineage.
AB  - The polar bear is the only living ursid with a fully carnivorous diet. Despite a
      number of well-documented craniodental adaptations for a diet of seal flesh and
      blubber, molecular and paleontological data indicate that this morphologically
      distinct species evolved less than a million years ago from the omnivorous brown
      bear. To better understand the evolution of this dietary specialization, we used
      phylogenetic tests to estimate the rate of morphological specialization in polar
      bears. We then used finite element analysis (FEA) to compare the limits of
      feeding performance in the polar bear skull to that of the phylogenetically and
      geographically close brown bear. Results indicate that extremely rapid evolution
      of semi-aquatic adaptations and dietary specialization in the polar bear lineage
      produced a cranial morphology that is weaker than that of brown bears and less
      suited to processing tough omnivorous or herbivorous diets. Our results suggest
      that continuation of current climate trends could affect polar bears by not only
      eliminating their primary food source, but also through competition with
      northward advancing, generalized brown populations for resources that they are
      ill-equipped to utilize.

PMID- 21079769
TI  - A scale-free structure prior for graphical models with applications in functional
      genomics.
AB  - The problem of reconstructing large-scale, gene regulatory networks from gene
      expression data has garnered considerable attention in bioinformatics over the
      past decade with the graphical modeling paradigm having emerged as a popular
      framework for inference. Analysis in a full Bayesian setting is contingent upon
      the assignment of a so-called structure prior-a probability distribution on
      networks, encoding a priori biological knowledge either in the form of
      supplemental data or high-level topological features. A key topological
      consideration is that a wide range of cellular networks are approximately scale
      free, meaning that the fraction, , of nodes in a network with degree is roughly
      described by a power-law with exponent between and . The standard practice,
      however, is to utilize a random structure prior, which favors networks with
      binomially distributed degree distributions. In this paper, we introduce a scale
      free structure prior for graphical models based on the formula for the
      probability of a network under a simple scale-free network model. Unlike the
      random structure prior, its scale-free counterpart requires a node labeling as a
      parameter. In order to use this prior for large-scale network inference, we
      design a novel Metropolis-Hastings sampler for graphical models that includes a
      node labeling as a state space variable. In a simulation study, we demonstrate
      that the scale-free structure prior outperforms the random structure prior at
      recovering scale-free networks while at the same time retains the ability to
      recover random networks. We then estimate a gene association network from gene
      expression data taken from a breast cancer tumor study, showing that scale-free
      structure prior recovers hubs, including the previously unknown hub SLC39A6,
      which is a zinc transporter that has been implicated with the spread of breast
      cancer to the lymph nodes. Our analysis of the breast cancer expression data
      underscores the value of the scale-free structure prior as an instrument to aid
      in the identification of candidate hub genes with the potential to direct the
      hypotheses of molecular biologists, and thus drive future experiments.

PMID- 21079770
TI  - Contraceptive use and method preference among women in Soweto, South Africa: the
      influence of expanding access to HIV care and treatment services.
AB  - OBJECTIVE: Preventing unintended pregnancy among HIV-positive women constitutes a
      critical and cost-effective approach to primary prevention of mother-to-child
      transmission of HIV and is a global public health priority for addressing the
      desperate state of maternal and child health in HIV hyper-endemic settings. We
      sought to investigate whether the prevalence of contraceptive use and method
      preferences varied by HIV status and receipt of highly active antiretroviral
      therapy (HAART) among women in Soweto, South Africa. METHODS: We used survey data
      from 563 sexually active, non-pregnant women (18-44 years) recruited from the
      Perinatal HIV Research Unit in Soweto (May-December, 2007); 171 women were HIV
      positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33),
      178 were HIV-positive and HAART-naive, and 214 were HIV-negative. Medical record
      review was conducted to confirm HIV status and clinical variables. Logistic
      regression models estimated adjusted associations between HIV status, receipt of
      HAART, and contraceptive use. RESULTS: Overall, 78% of women reported using
      contraception, with significant variation by HIV status: 86% of HAART users, 82%
      of HAART-naive women, and 69% of HIV-negative women (p<0.0001). In adjusted
      models, compared with HIV-negative women, women receiving HAART were
      significantly more likely to use contraception while HAART-naive women were non
      significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI:
      0.88, 2.85; respectively). Among HIV-positive women, HAART users were non
      significantly more likely to use contraception compared with HAART-naive women
      (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of
      barrier (primarily male condoms), permanent, and dual protection contraceptive
      methods. CONCLUSION: Among HIV-positive women receiving HAART, the observed
      higher prevalence of contraceptive use overall and condoms in particular promises
      to yield fewer unintended pregnancies and reduced risks of vertical and sexual
      HIV transmission. These findings highlight the potential of integrated HIV and
      reproductive health services to positively impact maternal, partner, and child
      health.

PMID- 21079771
TI  - Distribution analysis of hydrogenases in surface waters of marine and freshwater
      environments.
AB  - BACKGROUND: Surface waters of aquatic environments have been shown to both evolve
      and consume hydrogen and the ocean is estimated to be the principal natural
      source. In some marine habitats, H(2) evolution and uptake are clearly due to
      biological activity, while contributions of abiotic sources must be considered in
      others. Until now the only known biological process involved in H(2) metabolism
      in marine environments is nitrogen fixation. PRINCIPAL FINDINGS: We analyzed
      marine and freshwater environments for the presence and distribution of genes of
      all known hydrogenases, the enzymes involved in biological hydrogen turnover. The
      total genomes and the available marine metagenome datasets were searched for
      hydrogenase sequences. Furthermore, we isolated DNA from samples from the North
      Atlantic, Mediterranean Sea, North Sea, Baltic Sea, and two fresh water lakes and
      amplified and sequenced part of the gene encoding the bidirectional NAD(P)-linked
      hydrogenase. In 21% of all marine heterotrophic bacterial genomes from surface
      waters, one or several hydrogenase genes were found, with the membrane-bound H(2)
      uptake hydrogenase being the most widespread. A clear bias of hydrogenases to
      environments with terrestrial influence was found. This is exemplified by the
      cyanobacterial bidirectional NAD(P)-linked hydrogenase that was found in
      freshwater and coastal areas but not in the open ocean. SIGNIFICANCE: This study
      shows that hydrogenases are surprisingly abundant in marine environments. Due to
      its ecological distribution the primary function of the bidirectional NAD(P)
      linked hydrogenase seems to be fermentative hydrogen evolution. Moreover, our
      data suggests that marine surface waters could be an interesting source of oxygen
      resistant uptake hydrogenases. The respective genes occur in coastal as well as
      open ocean habitats and we presume that they are used as additional energy
      scavenging devices in otherwise nutrient limited environments. The membrane-bound
      H(2)-evolving hydrogenases might be useful as marker for bacteria living inside
      of marine snow particles.

PMID- 21079772
TI  - Changes in hepatic gene expression upon oral administration of taurine-conjugated
      ursodeoxycholic acid in ob/ob mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with
      considerable morbidities. Unfortunately, there is no currently available drug
      established to treat NAFLD. It was recently reported that intraperitoneal
      administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved
      hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA
      treatment on hepatic steatosis and associated changes in hepatic gene expression
      in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a
      day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic
      reticulum (ER) stress, and hepatic gene expression were examined in comparison
      with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the
      control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat
      stained by oil red O (44.2+/-5.8% vs. 21.1+/-10.4%, P<0.05), whereas there was no
      difference in body weight, oral glucose tolerance, insulin sensitivity, and ER
      stress. Microarray analysis of hepatic gene expression demonstrated that oral
      TUDCA treatment mainly decreased the expression of genes involved in de novo
      lipogenesis among the components of lipid homeostasis. At pathway levels, oral
      TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism
      in addition to lipid metabolism. In summary, oral TUDCA treatment decreased
      hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic
      pathways, particularly by reducing the expression of genes known to regulate de
      novo lipogenesis.

PMID- 21079773
TI  - Emotion modulation of visual attention: categorical and temporal characteristics.
AB  - BACKGROUND: Experimental research has shown that emotional stimuli can either
      enhance or impair attentional performance. However, the relative effects of
      specific emotional stimuli and the specific time course of these differential
      effects are unclear. METHODOLOGY/PRINCIPAL FINDINGS: In the present study,
      participants (n = 50) searched for a single target within a rapid serial visual
      presentation of images. Irrelevant fear, disgust, erotic or neutral images
      preceded the target by two, four, six, or eight items. At lag 2, erotic images
      induced the greatest deficits in subsequent target processing compared to other
      images, consistent with a large emotional attentional blink. Fear and disgust
      images also produced a larger attentional blinks at lag 2 than neutral images.
      Erotic, fear, and disgust images continued to induce greater deficits than
      neutral images at lag 4 and 6. However, target processing deficits induced by
      erotic, fear, and disgust images at intermediate lags (lag 4 and 6) did not
      consistently differ from each other. In contrast to performance at lag 2, 4, and
      6, enhancement in target processing for emotional stimuli was observed in
      comparison to neutral stimuli at lag 8. CONCLUSIONS/SIGNIFICANCE: These findings
      suggest that task-irrelevant emotion information, particularly erotica, impairs
      intentional allocation of attention at early temporal stages, but at later
      temporal stages, emotional stimuli can have an enhancing effect on directed
      attention. These data suggest that the effects of emotional stimuli on attention
      can be both positive and negative depending upon temporal factors.

PMID- 21079774
TI  - Defects in innate immunity render breast cancer initiating cells permissive to
      oncolytic adenovirus.
AB  - BACKGROUND: Cancer stem cells/initiating cells (CSC/CIC), are thought to exist as
      a small population in malignant tissues. They are resistant to conventional
      cancer treatments and possibly underlie post-treatment relapse. The CIC
      population can be targeted with capsid modified oncolytic adenoviruses.
      METHODOLOGY/PRINCIPAL FINDINGS: We studied the mechanisms of innate immunity to
      oncolytic adenovirus Ad5/3-Delta24 in conventional treatment resistant non-CIC
      breast cancer cells, breast cancer CD44(+)/CD24(-/low) CIC population and normal
      breast tissue CD44(+)/CD24(-/low) stem cells. We compared virus recognition by
      pattern recognition receptors for adenovirus, Toll-like receptors (TLR) 2 and 9
      and virus induced type I interferon (IFN) response regulation in these cell
      types. We show TLR mediated virus recognition in these non-immune cell types.
      Normal tissue stem cells have intact type I IFN signaling. Furthermore, TLR9 and
      TLR2 reside constantly in recognition sites, implying constant activation. In
      contrast, breast cancer CD44(+)/CD24(-/low) CIC have dysregulated innate immune
      responses featuring dysfunctional virus recognition caused by impaired
      trafficking of TLR9 and cofactor MyD88 and the absence of TLR2, having a
      deleterious impact on TLR pattern recognition receptor signaling. Furthermore,
      the CIC have increased inhibitory signaling via the suppressor of cytokine
      signaling/Tyro3/Axl/Mer receptor tyrosine kinase (SOCS/TAM) pathway. These
      defects in contribute to dysfunctional induction of type I IFN response in CIC
      and therefore permissivity to oncolytic adenovirus. CONCLUSIONS/SIGNIFICANCE:
      CICs may underlie the incurable nature of relapsed or metastatic cancers and are
      therefore an important target regarding diagnostic and prognostic aspects as well
      as treatment of the disease. This study addresses the mechanisms of innate
      infection immunity in stem cells deepening the understanding of stem cell biology
      and may benefit not only virotherapy but also immunotherapy in general.

PMID- 21079775
TI  - Funduscopy in adult zebrafish and its application to isolate mutant strains with
      ocular defects.
AB  - Funduscopy is one of the most commonly used diagnostic tools in the ophthalmic
      practice, allowing for a ready assessment of pathological changes in the retinal
      vasculature and the outer retina. This non-invasive technique has so far been
      rarely used in animal model for ophthalmic diseases, albeit its potential as a
      screening assay in genetic screens. The zebrafish (Danio rerio) is well suited
      for such genetic screens for ocular alterations. Therefore we developed
      funduscopy in adult zebrafish and employed it as a screening tool to find
      alterations in the anterior segment and the fundus of the eye of genetically
      modified adult animals.A stereomicroscope with coaxial reflected light
      illumination was used to obtain fundus color images of the zebrafish. In order to
      find lens and retinal alterations, a pilot screen of 299 families of the F3
      generation of ENU-treated adult zebrafish was carried out.Images of the fundus of
      the eye and the anterior segment can be rapidly obtained and be used to identify
      alterations in genetically modified animals. A number of putative mutants with
      cataracts, defects in the cornea, eye pigmentation, ocular vessels and retina
      were identified. This easily implemented method can also be used to obtain fundus
      images from rodent retinas.In summary, we present funduscopy as a valuable tool
      to analyse ocular abnormalities in adult zebrafish and other small animal models.
      A proof of principle screen identified a number of putative mutants, making
      funduscopy based screens in zebrafish feasible.

PMID- 21079776
TI  - A bacteriophage-related chimeric marine virus infecting abalone.
AB  - Marine viruses shape microbial communities with the most genetic diversity in the
      sea by multiple genetic exchanges and infect multiple marine organisms. Here we
      provide proof from experimental infection that abalone shriveling syndrome
      associated virus (AbSV) can cause abalone shriveling syndrome. This malady
      produces histological necrosis and abnormally modified macromolecules (hemocyanin
      and ferritin). The AbSV genome is a 34.952-kilobase circular double-stranded DNA,
      containing putative genes with similarity to bacteriophages, eukaryotic viruses,
      bacteria and endosymbionts. Of the 28 predicted open reading frames (ORFs), eight
      ORF-encoded proteins have identifiable functional homologues. The 4 ORF products
      correspond to a predicted terminase large subunit and an endonuclease in
      bacteriophage, and both an integrase and an exonuclease from bacteria. The other
      four proteins are homologous to an endosymbiont-derived helicase, primase, single
      stranded binding (SSB) protein, and thymidylate kinase, individually.
      Additionally, AbSV exhibits a common gene arrangement similar to the majority of
      bacteriophages. Unique to AbSV, the viral genome also contains genes associated
      with bacterial outer membrane proteins and may lack the structural protein
      encoding ORFs. Genomic characterization of AbSV indicates that it may represent a
      transitional form of microbial evolution from viruses to bacteria.

PMID- 21079777
TI  - ATP changes the fluorescence lifetime of cyan fluorescent protein via an
      interaction with His148.
AB  - Recently, we described that ATP induces changes in YFP/CFP fluorescence
      intensities of Fluorescence Resonance Energy Transfer (FRET) sensors based on CFP
      YFP. To get insight into this phenomenon, we employed fluorescence lifetime
      spectroscopy to analyze the influence of ATP on these fluorescent proteins in
      more detail. Using different donor and acceptor pairs we found that ATP only
      affected the CFP-YFP based versions. Subsequent analysis of purified monomers of
      the used proteins showed that ATP has a direct effect on the fluorescence
      lifetime properties of CFP. Since the fluorescence lifetime analysis of CFP is
      rather complicated by the existence of different lifetimes, we tested a variant
      of CFP, i.e. Cerulean, as a monomer and in our FRET constructs. Surprisingly,
      this CFP variant shows no ATP concentration dependent changes in the fluorescence
      lifetime. The most important difference between CFP and Cerulean is a histidine
      residue at position 148. Indeed, changing this histidine in CFP into an aspartic
      acid results in identical fluorescence properties as observed for the Cerulean
      fluorescent based FRET sensor. We therefore conclude that the changes in
      fluorescence lifetime of CFP are affected specifically by possible electrostatic
      interactions of the negative charge of ATP with the positively charged histidine
      at position 148. Clearly, further physicochemical characterization is needed to
      explain the sensitivity of CFP fluorescence properties to changes in
      environmental (i.e. ATP concentrations) conditions.

PMID- 21079778
TI  - Down-regulation of serum/glucocorticoid regulated kinase 1 in colorectal tumours
      is largely independent of promoter hypermethylation.
AB  - BACKGROUND: We have previously shown that serum/glucocorticoid regulated kinase 1
      (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal
      tissue. As hyper-methylation of promoter regions is a well-known mechanism of
      gene silencing in cancer, we tested whether the SGK1 promoter region was
      methylated in colonic tumour samples. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated the methylation profile of the two CpG islands present in the
      promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by
      sequencing clones of bisulphite-treated DNA samples. We further confirmed our
      findings in a panel of 10 normal and 10 tumour colonic tissue samples of human
      origin. We observed CpG methylation only in the smaller and more distal CpG
      island in the promoter region of SGK1 in both normal and tumour samples of
      colonic origin. We further identified a single nucleotide polymorphism (SNP,
      rs1743963) which affects methylation of the corresponding CpG.
      CONCLUSIONS/SIGNIFICANCE: Our results show that even though partial methylation
      of the promoter region of SGK1 is present, this does not account for the
      different expression levels seen between normal and tumour tissue.

PMID- 21079779
TI  - Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis
      by influencing EGF receptor signaling.
AB  - Increased versican expression in breast tumors is predictive of relapse and has
      negative impact on survival rates. The C-terminal G3 domain of versican
      influences local and systemic tumor invasiveness in pre-clinical murine models.
      However, the mechanism(s) by which G3 influences breast tumor growth and
      metastasis is not well characterized. Here we evaluated the expression of
      versican in mouse mammary tumor cell lines observing that 4T1 cells expressed
      highest levels while 66c14 cells expressed low levels. We exogenously expressed a
      G3 construct in 66c14 cells and analyzed its effects on cell proliferation,
      migration, cell cycle progression, and EGFR signaling. Experiments in a syngeneic
      orthotopic animal model demonstrated that G3 promoted tumor growth and systemic
      metastasis in vivo. Activation of pERK correlated with high levels of G3
      expression. In vitro, G3 enhanced breast cancer cell proliferation and migration
      by up-regulating EGFR signaling, and enhanced cell motility through chemotactic
      mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. G3
      expressing cells demonstrated increased CDK2 and GSK-3beta (S9P) expression,
      which were related to cell growth. The activity of G3 on mouse mammary tumor cell
      growth, migration and its effect on spontaneous metastasis to bone in an
      orthotopic model was modulated by up-regulating the EGFR-mediated signaling
      pathway. Taken together, EGFR-signaling appears to be an important pathway in
      versican G3-mediated breast cancer tumor invasiveness and metastasis.

PMID- 21079781
TI  - Increasing incidence of Geomyces destructans fungus in bats from the Czech
      Republic and Slovakia.
AB  - BACKGROUND: White-nose syndrome is a disease of hibernating insectivorous bats
      associated with the fungus Geomyces destructans. It first appeared in North
      America in 2006, where over a million bats died since then. In Europe, G.
      destructans was first identified in France in 2009. Its distribution, infection
      dynamics, and effects on hibernating bats in Europe are largely unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We screened hibernacula in the Czech Republic and
      Slovakia for the presence of the fungus during the winter seasons of 2008/2009
      and 2009/2010. In winter 2009/2010, we found infected bats in 76 out of 98
      surveyed sites, in which the majority had been previously negative. A
      photographic record of over 6000 hibernating bats, taken since 1994, revealed
      bats with fungal growths since 1995; however, the incidence of such bats
      increased in Myotis myotis from 2% in 2007 to 14% by 2010. Microscopic,
      cultivation and molecular genetic evaluations confirmed the identity of the
      recently sampled fungus as G. destructans, and demonstrated its continuous
      distribution in the studied area. At the end of the hibernation season we
      recorded pathologic changes in the skin of the affected bats, from which the
      fungus was isolated. We registered no mass mortality caused by the fungus, and
      the recorded population decline in the last two years of the most affected
      species, M. myotis, is within the population trend prediction interval.
      CONCLUSIONS/SIGNIFICANCE: G. destructans was found to be widespread in the Czech
      Republic and Slovakia, with an epizootic incidence in bats during the most recent
      years. Further development of the situation urgently requires a detailed pan
      European monitoring scheme.

PMID- 21079780
TI  - Environmental acidification drives S. pyogenes pilus expression and microcolony
      formation on epithelial cells in a FCT-dependent manner.
AB  - Group A Streptococcus (GAS, Streptococcus pyogenes) is a gram-positive human
      pathogen responsible for a diverse variety of diseases, including pharyngitis,
      skin infections, invasive necrotizing fasciitis and autoimmune sequelae. We have
      recently shown that GAS cell adhesion and biofilm formation is associated with
      the presence of pili on the surface of these bacteria. GAS pilus proteins are
      encoded in the FCT (Fibronectin-Collagen-T antigen) genomic region, of which nine
      different variants have been identified so far. In the present study we undertook
      a global analysis of GAS isolates representing the majority of FCT-variants to
      investigate the effect of environmental growth conditions on their capacity to
      form multicellular communities. For FCT-types 2, 3, 5 and 6 and a subset of FCT-4
      strains, we observed that acidification resulting from fermentative sugar
      metabolism leads to an increased ability of the bacteria to form biofilm on
      abiotic surfaces and microcolonies on epithelial cells. The higher biofilm
      forming capacity at low environmental pH was directly associated with an enhanced
      expression of the genes encoding the pilus components and of their transcription
      regulators. The data indicate that environmental pH affects the expression of
      most pilus types and thereby the formation of multicellular cell-adhering
      communities that assist the initial steps of GAS infection.

PMID- 21079782
TI  - Improved detection of rare genetic variants for diseases.
AB  - Technology advances have promoted gene-based sequencing studies with the aim of
      identifying rare mutations responsible for complex diseases. A complication in
      these types of association studies is that the vast majority of non-synonymous
      mutations are believed to be neutral to phenotypes. It is thus critical to
      distinguish potential causative variants from neutral variation before performing
      association tests. In this study, we used existing predicting algorithms to
      predict functional amino acid substitutions, and incorporated that information
      into association tests. Using simulations, we comprehensively studied the effects
      of several influential factors, including the sensitivity and specificity of
      functional variant predictions, number of variants, and proportion of causative
      variants, on the performance of association tests. Our results showed that
      incorporating information regarding functional variants obtained from existing
      prediction algorithms improves statistical power under certain conditions,
      particularly when the proportion of causative variants is moderate. The
      application of the proposed tests to a real sequencing study confirms our
      conclusions. Our work may help investigators who are planning to pursue gene
      based sequencing studies.

PMID- 21079783
TI  - Rapid change in articulatory lip movement induced by preceding auditory feedback
      during production of bilabial plosives.
AB  - BACKGROUND: There has been plentiful evidence of kinesthetically induced rapid
      compensation for unanticipated perturbation in speech articulatory movements.
      However, the role of auditory information in stabilizing articulation has been
      little studied except for the control of voice fundamental frequency, voice
      amplitude and vowel formant frequencies. Although the influence of auditory
      information on the articulatory control process is evident in unintended speech
      errors caused by delayed auditory feedback, the direct and immediate effect of
      auditory alteration on the movements of articulators has not been clarified.
      METHODOLOGY/PRINCIPAL FINDINGS: This work examined whether temporal changes in
      the auditory feedback of bilabial plosives immediately affects the subsequent lip
      movement. We conducted experiments with an auditory feedback alteration system
      that enabled us to replace or block speech sounds in real time. Participants were
      asked to produce the syllable /pa/ repeatedly at a constant rate. During the
      repetition, normal auditory feedback was interrupted, and one of three pre
      recorded syllables /pa/, /Phia/, or /pi/, spoken by the same participant, was
      presented once at a different timing from the anticipated production onset, while
      no feedback was presented for subsequent repetitions. Comparisons of the labial
      distance trajectories under altered and normal feedback conditions indicated that
      the movement quickened during the short period immediately after the alteration
      onset, when /pa/ was presented 50 ms before the expected timing. Such change was
      not significant under other feedback conditions we tested.
      CONCLUSIONS/SIGNIFICANCE: The earlier articulation rapidly induced by the
      progressive auditory input suggests that a compensatory mechanism helps to
      maintain a constant speech rate by detecting errors between the internally
      predicted and actually provided auditory information associated with self
      movement. The timing- and context-dependent effects of feedback alteration
      suggest that the sensory error detection works in a temporally asymmetric window
      where acoustic features of the syllable to be produced may be coded.

PMID- 21079784
TI  - Decreased ratio of Treg cells to Th17 cells correlates with HBV DNA suppression
      in chronic hepatitis B patients undergoing entecavir treatment.
AB  - BACKGROUND: Treatment with nucleotide analogs is known to be effective in
      inhibiting HBV replication; however, patients with chronic hepatitis B (CHB)
      often show a wide range of clinical responses to these drugs. Therefore, the
      identification of an early immunologic marker associated with the clinical
      outcomes in such cases is critical for the improved clinical management. In our
      study, we aimed to investigate whether the viral load in CHB patients affected
      the ratio of the number of regulatory T cells (Tregs) to the number of
      interleukin-17-producing helper (Th17) cells. Further, we evaluated the clinical
      implications of the alterations in this ratio. METHODOLOGY/PRINCIPAL FINDINGS:
      Nine patients seropositive for hepatitis B e antigen received entecavir
      monotherapy for 12 months and the percentages of Tregs and Th17 cells as well as
      the HBV-specific IL-17 productions in these patients were longitudinally
      analyzed. The entecavir-induced suppression of HBV replication was accompanied by
      a rapid increase in the number of Th17 cells, together with a decrease in Treg
      cells, which lead to a significant reduction of Treg/Th17 ratios. In addition,
      peripheral blood mononuclear cells (PBMCs) exhibited a decreased IL-17 production
      upon stimulation with the HBV core antigen in vitro. CONCLUSIONS: The inhibition
      of viral replication results in an increase in Th17 cells and concomitant
      decrease in Treg cells. This imbalance of Treg cells to Th17 cells might have an
      important role in HBV persistence during entecavir treatment.

PMID- 21079785
TI  - An incomplete TCA cycle increases survival of Salmonella Typhimurium during
      infection of resting and activated murine macrophages.
AB  - BACKGROUND: In comparison to the comprehensive analyses performed on virulence
      gene expression, regulation and action, the intracellular metabolism of
      Salmonella during infection is a relatively under-studied area. We investigated
      the role of the tricarboxylic acid (TCA) cycle in the intracellular replication
      of Salmonella Typhimurium in resting and activated macrophages, epithelial cells,
      and during infection of mice. METHODOLOGY/PRINCIPAL FINDINGS: We constructed
      deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh,
      sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net
      intracellular replication in resting and activated murine macrophages compared to
      the wild-type. In contrast, an epithelial cell infection model showed that the S.
      Typhimurium DeltasucCD and DeltagltA strains had reduced net intracellular
      replication compared to the wild-type. The glyoxylate shunt was not responsible
      for the net increased replication of the TCA cycle mutants within resting
      macrophages. We also confirmed that, in a murine infection model, the S.
      Typhimurium DeltasucAB and DeltasucCD strains are attenuated for virulence.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that disruption of the TCA cycle
      increases the ability of S. Typhimurium to survive within resting and activated
      murine macrophages. In contrast, epithelial cells are non-phagocytic cells and
      unlike macrophages cannot mount an oxidative and nitrosative defence response
      against pathogens; our results show that in HeLa cells the S. Typhimurium TCA
      cycle mutant strains show reduced or no change in intracellular levels compared
      to the wild-type. The attenuation of the S. Typhimurium DeltasucAB and DeltasucCD
      mutants in mice, compared to their increased net intracellular replication in
      resting and activated macrophages suggest that Salmonella may encounter
      environments within the host where a complete TCA cycle is advantageous.

PMID- 21079786
TI  - The structural complexity of the human BORIS gene in gametogenesis and cancer.
AB  - BACKGROUND: BORIS/CTCFL is a paralogue of CTCF, the major epigenetic regulator of
      vertebrate genomes. BORIS is normally expressed only in germ cells but is
      aberrantly activated in numerous cancers. While recent studies demonstrated that
      BORIS is a transcriptional activator of testis-specific genes, little is
      generally known about its biological and molecular functions.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we show that BORIS is expressed as 23
      isoforms in germline and cancer cells. The isoforms are comprised of alternative
      N- and C-termini combined with varying numbers of zinc fingers (ZF) in the DNA
      binding domain. The patterns of BORIS isoform expression are distinct in germ and
      cancer cells. Isoform expression is activated by downregulation of CTCF,
      upregulated by reduction in CpG methylation caused by inactivation of DNMT1 or
      DNMT3b, and repressed by activation of p53. Studies of ectopically expressed
      isoforms showed that all are translated and localized to the nucleus. Using the
      testis-specific cerebroside sulfotransferase (CST) promoter and the IGF2/H19
      imprinting control region (ICR), it was shown that binding of BORIS isoforms to
      DNA targets in vitro is methylation-sensitive and depends on the number and
      specific composition of ZF. The ability to bind target DNA and the presence of a
      specific long amino terminus (N258) in different isoforms are necessary and
      sufficient to activate CST transcription. Comparative sequence analyses revealed
      an evolutionary burst in mammals with strong conservation of BORIS isoproteins
      among primates. CONCLUSIONS: The extensive repertoire of spliced BORIS variants
      in humans that confer distinct DNA binding and transcriptional activation
      properties, and their differential patterns of expression among germ cells and
      neoplastic cells suggest that the gene is involved in a range of functionally
      important aspects of both normal gametogenesis and cancer development. In
      addition, a burst in isoform diversification may be evolutionarily tied to unique
      aspects of primate speciation.

PMID- 21079787
TI  - Evolution of linked avirulence effectors in Leptosphaeria maculans is affected by
      genomic environment and exposure to resistance genes in host plants.
AB  - Brassica napus (canola) cultivars and isolates of the blackleg fungus,
      Leptosphaeria maculans interact in a 'gene for gene' manner whereby plant
      resistance (R) genes are complementary to pathogen avirulence (Avr) genes.
      Avirulence genes encode proteins that belong to a class of pathogen molecules
      known as effectors, which includes small secreted proteins that play a role in
      disease. In Australia in 2003 canola cultivars with the Rlm1 resistance gene
      suffered a breakdown of disease resistance, resulting in severe yield losses.
      This was associated with a large increase in the frequency of virulence alleles
      of the complementary avirulence gene, AvrLm1, in fungal populations.
      Surprisingly, the frequency of virulence alleles of AvrLm6 (complementary to
      Rlm6) also increased dramatically, even though the cultivars did not contain
      Rlm6. In the L. maculans genome, AvrLm1 and AvrLm6 are linked along with five
      other genes in a region interspersed with transposable elements that have been
      degenerated by Repeat-Induced Point (RIP) mutations. Analyses of 295 Australian
      isolates showed deletions, RIP mutations and/or non-RIP derived amino acid
      substitutions in the predicted proteins encoded by these seven genes. The degree
      of RIP mutations within single copy sequences in this region was proportional to
      their proximity to the degenerated transposable elements. The RIP alleles were
      monophyletic and were present only in isolates collected after resistance
      conferred by Rlm1 broke down, whereas deletion alleles belonged to several
      polyphyletic lineages and were present before and after the resistance breakdown.
      Thus, genomic environment and exposure to resistance genes in B. napus has
      affected the evolution of these linked avirulence genes in L. maculans.

PMID- 21079788
TI  - Human cytomegalovirus induces TGF-beta1 activation in renal tubular epithelial
      cells after epithelial-to-mesenchymal transition.
AB  - Human cytomegalovirus (HCMV) infection is associated epidemiologically with poor
      outcome of renal allografts due to mechanisms which remain largely undefined.
      Transforming growth factor-beta1 (TGF-beta1), a potent fibrogenic cytokine, is
      more abundant in rejecting renal allografts that are infected with either HCMV or
      rat CMV as compared to uninfected, rejecting grafts. TGF-beta1 induces renal
      fibrosis via epithelial-to-mesenchymal transition (EMT) of renal epithelial
      cells, a process by which epithelial cells acquire mesenchymal characteristics
      and a migratory phenotype, and secrete molecules associated with extracellular
      matrix deposition and remodeling. We report that human renal tubular epithelial
      cells infected in vitro with HCMV and exposed to TGF-beta1 underwent morphologic
      and transcriptional changes of EMT, similar to uninfected cells. HCMV infected
      cells after EMT also activated extracellular latent TGF-beta1 via induction of
      MMP-2. Renal epithelial cells transiently transfected with only the HCMV IE1 or
      IE2 open reading frames and stimulated to undergo EMT also induced TGF-beta1
      activation associated with MMP-2 production, suggesting a role for these viral
      gene products in MMP-2 production. Consistent with the function of these
      immediate early gene products, the antiviral agents ganciclovir and foscarnet did
      not inhibit TGF-beta1 production after EMT by HCMV infected cells. These results
      indicate that HCMV infected renal tubular epithelial cells can undergo EMT after
      exposure to TGF-beta1, similar to uninfected renal epithelial cells, but that
      HCMV infection by inducing active TGF-beta1 may potentiate renal fibrosis. Our
      findings provide in vitro evidence for a pathogenic mechanism that could explain
      the clinical association between HCMV infection, TGF-beta1, and adverse renal
      allograft outcome.

PMID- 21079789
TI  - The Caenorhabditis elegans Kinesin-3 motor UNC-104/KIF1A is degraded upon loss of
      specific binding to cargo.
AB  - UNC-104/KIF1A is a Kinesin-3 motor that transports synaptic vesicles from the
      cell body towards the synapse by binding to PI(4,5)P(2) through its PH domain.
      The fate of the motor upon reaching the synapse is not known. We found that wild
      type UNC-104 is degraded at synaptic regions through the ubiquitin pathway and is
      not retrogradely transported back to the cell body. As a possible means to
      regulate the motor, we tested the effect of cargo binding on UNC-104 levels. The
      unc-104(e1265) allele carries a point mutation (D1497N) in the PI(4,5)P(2)
      binding pocket of the PH domain, resulting in greatly reduced preferential
      binding to PI(4,5)P(2)in vitro and presence of very few motors on pre-synaptic
      vesicles in vivo. unc-104(e1265) animals have poor locomotion irrespective of in
      vivo PI(4,5)P(2) levels due to reduced anterograde transport. Moreover, they show
      highly reduced levels of UNC-104 in vivo. To confirm that loss of cargo binding
      specificity reduces motor levels, we isolated two intragenic suppressors with
      compensatory mutations within the PH domain. These show partial restoration of in
      vitro preferential PI(4,5)P(2) binding and presence of more motors on pre
      synaptic vesicles in vivo. These animals show improved locomotion dependent on in
      vivo PI(4,5)P(2) levels, increased anterograde transport, and partial restoration
      of UNC-104 protein levels in vivo. For further proof, we mutated a conserved
      residue in one suppressor background. The PH domain in this triple mutant lacked
      in vitro PI(4,5)P(2) binding specificity, and the animals again showed locomotory
      defects and reduced motor levels. All allelic variants show increased UNC-104
      levels upon blocking the ubiquitin pathway. These data show that inability to
      bind cargo can target motors for degradation. In view of the observed degradation
      of the motor in synaptic regions, this further suggests that UNC-104 may get
      degraded at synapses upon release of cargo.

PMID- 21079790
TI  - The Arabidopsis resistance-like gene SNC1 is activated by mutations in SRFR1 and
      contributes to resistance to the bacterial effector AvrRps4.
AB  - The SUPPRESSOR OF rps4-RLD1 (SRFR1) gene was identified based on enhanced AvrRps4
      triggered resistance in the naturally susceptible Arabidopsis accession RLD. No
      other phenotypic effects were recorded, and the extent of SRFR1 involvement in
      regulating effector-triggered immunity was unknown. Here we show that mutations
      in SRFR1 in the accession Columbia-0 (Col-0) lead to severe stunting and
      constitutive expression of the defense gene PR1. These phenotypes were
      temperature-dependent. A cross between srfr1-1 (RLD background) and srfr1-4 (Col
      0) showed that stunting was caused by a recessive locus in Col-0. Mapping and
      targeted crosses identified the Col-0-specific resistance gene SNC1 as the locus
      that causes stunting. SRFR1 was proposed to function as a transcriptional
      repressor, and SNC1 is indeed overexpressed in srfr1-4. Interestingly, co
      regulated genes in the SNC1 cluster are also upregulated in the srfr1-4 snc1-11
      double mutant, indicating that the overexpression of SNC1 is not a secondary
      effect of constitutive defense activation. In addition, a Col-0 RPS4 mutant
      showed full susceptibility to bacteria expressing avrRps4 at 24 degrees C but not
      at 22 degrees C, while RLD susceptibility was not temperature-dependent. The rps4
      2 snc1-11 double mutant showed increased, but not full, susceptibility at 22
      degrees C, indicating that additional cross-talk between resistance pathways may
      exist. Intriguingly, when transiently expressed in Nicotiana benthamiana, SRFR1,
      RPS4 and SNC1 are in a common protein complex in a cytoplasmic microsomal
      compartment. Our results highlight SRFR1 as a convergence point in at least a
      subset of TIR-NBS-LRR protein-mediated immunity in Arabidopsis. Based on the
      cross-talk evident from our results, they also suggest that reports of
      constitutive resistance phenotypes in Col-0 need to consider the possible
      involvement of SNC1.

PMID- 21079791
TI  - The functional interplay between protein kinase CK2 and CCA1 transcriptional
      activity is essential for clock temperature compensation in Arabidopsis.
AB  - Circadian rhythms are daily biological oscillations driven by an endogenous
      mechanism known as circadian clock. The protein kinase CK2 is one of the few
      clock components that is evolutionary conserved among different taxonomic groups.
      CK2 regulates the stability and nuclear localization of essential clock proteins
      in mammals, fungi, and insects. Two CK2 regulatory subunits, CKB3 and CKB4, have
      been also linked with the Arabidopsis thaliana circadian system. However, the
      biological relevance and the precise mechanisms of CK2 function within the plant
      clockwork are not known. By using ChIP and Double-ChIP experiments together with
      in vivo luminescence assays at different temperatures, we were able to identify a
      temperature-dependent function for CK2 modulating circadian period length. Our
      study uncovers a previously unpredicted mechanism for CK2 antagonizing the key
      clock regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1). CK2 activity does not alter
      protein accumulation or subcellular localization but interferes with CCA1 binding
      affinity to the promoters of the oscillator genes. High temperatures enhance the
      CCA1 binding activity, which is precisely counterbalanced by the CK2 opposing
      function. Altering this balance by over-expression, mutation, or pharmacological
      inhibition affects the temperature compensation profile, providing a mechanism by
      which plants regulate circadian period at changing temperatures. Therefore, our
      study establishes a new model demonstrating that two opposing and temperature
      dependent activities (CCA1-CK2) are essential for clock temperature compensation
      in Arabidopsis.

PMID- 21079792
TI  - Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin
      and monoallelic expression of critical genes.
AB  - As a first step towards discovery of genes expressed from only one allele in the
      CNS, we used a tiling array assay for DNA sequences that are both methylated and
      unmethylated (the MAUD assay). We analyzed regulatory regions of the entire mouse
      brain transcriptome, and found that approximately 10% of the genes assayed showed
      dual DNA methylation patterns. They include a large subset of genes that display
      marks of both active and silent, i.e., poised, chromatin during development,
      consistent with a link between differential DNA methylation and lineage-specific
      differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes
      whose function is of relevance to CNS development and/or disorders were tested
      for allele-specific expression in F(1) hybrid clonal neural stem cell (NSC)
      lines. Eight MAUD hits and one additional gene showed such expression. They
      include Lgi1, which causes a subtype of inherited epilepsy that displays
      autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell
      line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy;
      Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane
      chondroitin sulfate proteoglycan associated with malignant melanoma and
      astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show
      preferential expression of the same allele in all clonal NSC lines tested. The
      other six genes show a stochastic pattern of monoallelic expression in some NSC
      lines and bi-allelic expression in others. These results support the estimate
      that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and
      demonstrate that the group includes genes implicated in major disorders of the
      CNS as well as neurodevelopment.

PMID- 21079793
TI  - Allele polymorphism and haplotype diversity of HLA-A, -B and -DRB1 loci in
      sequence-based typing for Chinese Uyghur ethnic group.
AB  - BACKGROUND: Previous studies indicate that the frequency distributions of HLA
      alleles and haplotypes vary from one ethnic group to another or between the
      members of the same ethnic group living in different geographic areas. It is
      necessary and meaningful to study the high-resolution allelic and haplotypic
      distributions of HLA loci in different groups. METHODOLOGY/PRINCIPAL FINDINGS:
      High-resolution HLA typing for the Uyghur ethnic minority group using polymerase
      chain reaction-sequence-based-typing method was first reported. HLA-A, -B and 
      DRB1 allelic distributions were determined in 104 unrelated healthy Uyghur
      individuals and haplotypic frequencies and linkage disequilibrium parameters for
      HLA loci were estimated using the maximum-likelihood method. A total of 35 HLA-A,
      51 HLA-B and 33 HLA-DRB1 alleles were identified at the four-digit level in the
      population. High frequency alleles were HLA-A*1101 (13.46%), A*0201 (12.50%),
      A*0301 (10.10%); HLA-B*5101(8.17%), B*3501(6.73%), B*5001 (6.25%); HLA-DRB1*0701
      (16.35%), DRB1*1501 (8.65%) and DRB1*0301 (7.69%). The two-locus haplotypes at
      the highest frequency were HLA-A*3001-B*1302 (2.88%), A*2402-B*5101 (2.86%); HLA
      B*5001-DRB1*0701 (4.14%) and B*0702-DRB1*1501 (3.37%). The three-locus haplotype
      at the highest frequency was HLA-A*3001-B*1302-DRB1*0701(2.40%). Significantly
      high linkage disequilibrium was observed in six two-locus haplotypes, with their
      corresponding relative linkage disequilibrium parameters equal to 1. Neighbor
      joining phylogenetic tree between the Uyghur group and other previously reported
      populations was constructed on the basis of standard genetic distances among the
      populations calculated using the four-digit sequence-level allelic frequencies at
      HLA-A, HLA-B and HLA-DRB1 loci. The phylogenetic analyses reveal that the Uyghur
      group belongs to the northwestern Chinese populations and is most closely related
      to the Xibe group, and then to Kirgiz, Hui, Mongolian and Northern Han.
      CONCLUSIONS/SIGNIFICANCE: The present findings could be useful to elucidate the
      genetic background of the population and to provide valuable data for HLA
      matching in clinical bone marrow transplantation, HLA-linked disease-association
      studies, population genetics, human identification and paternity tests in
      forensic sciences.

PMID- 21079794
TI  - Human SHBG mRNA translation is modulated by alternative 5'-non-coding exons 1A
      and 1B.
AB  - BACKGROUND: The human sex hormone-binding globulin (SHBG) gene comprises at least
      6 different transcription units (TU-1, -1A, -1B, -1C, -1D and -1E), and is
      regulated by no less than 6 different promoters. The best characterized are TU-1
      and TU-1A: TU-1 is responsible for producing plasma SHBG, while TU-1A is
      transcribed and translated in the testis. Transcription of the recently described
      TU-1B, -1C, and -1D has been demonstrated in human prostate tissue and prostate
      cancer cell lines, as well as in other human cell lines such as HeLa, HepG2, HeK
      293, CW 9019 and imr 32. However, there are no reported data demonstrating their
      translation. In the present study, we aimed to determine whether TU-1A and TU-1B
      are indeed translated in the human prostate and whether 5' UTR exons 1A and 1B
      differently regulate SHBG translation. RESULTS: Cis-regulatory elements that
      could potentially regulate translation were identified within the 5'UTRs of SHBG
      TU-1A and TU-1B. Although full-length SHBG TU-1A and TU-1B mRNAs were present in
      prostate cancer cell lines, the endogenous SHBG protein was not detected by
      western blot in any of them. LNCaP prostate cancer cells transfected with several
      SHBG constructs containing exons 2 to 8 but lacking the 5'UTR sequence did show
      SHBG translation, whereas inclusion of the 5'UTR sequences of either exon 1A or
      1B caused a dramatic decrease in SHBG protein levels. The molecular weight of
      SHBG did not vary between cells transfected with constructs with or without the
      5'UTR sequence, thus confirming that the first in-frame ATG of exon 2 is the
      translation start site of TU-1A and TU-1B. CONCLUSIONS: The use of alternative
      SHBG first exons 1A and 1B differentially inhibits translation from the ATG
      situated in exon 2, which codes for methionine 30 of transcripts that begin with
      the exon 1 sequence.

PMID- 21079795
TI  - A voltage-sensitive dye-based assay for the identification of differentiated
      neurons derived from embryonic neural stem cell cultures.
AB  - BACKGROUND: Pluripotent and multipotent stem cells hold great therapeutical
      promise for the replacement of degenerated tissue in neurological diseases. To
      fulfill that promise we have to understand the mechanisms underlying the
      differentiation of multipotent cells into specific types of neurons. Embryonic
      stem cell (ESC) and embryonic neural stem cell (NSC) cultures provide a valuable
      tool to study the processes of neural differentiation, which can be assessed
      using immunohistochemistry, gene expression, Ca(2+)-imaging or electrophysiology.
      However, indirect methods such as protein and gene analysis cannot provide direct
      evidence of neuronal functionality. In contrast, direct methods such as
      electrophysiological techniques are well suited to produce direct evidence of
      neural functionality but are limited to the study of a few cells on a culture
      plate. METHODOLOGY/PRINCIPAL FINDINGS: In this study we describe a novel method
      for the detection of action potential-capable neurons differentiated from
      embryonic NSC cultures using fast voltage-sensitive dyes (VSD). We found that the
      use of extracellularly applied VSD resulted in a more detailed labeling of
      cellular processes compared to calcium indicators. In addition, VSD changes in
      fluorescence translated precisely to action potential kinetics as assessed by the
      injection of simulated slow and fast sodium currents using the dynamic clamp
      technique. We further demonstrate the use of a finite element model of the NSC
      culture cover slip for optimizing electrical stimulation parameters.
      CONCLUSIONS/SIGNIFICANCE: Our method allows for a repeatable fast and accurate
      stimulation of neurons derived from stem cell cultures to assess their
      differentiation state, which is capable of monitoring large amounts of cells
      without harming the overall culture.

PMID- 21079796
TI  - Ancestral informative marker selection and population structure visualization
      using sparse Laplacian eigenfunctions.
AB  - Identification of a small panel of population structure informative markers can
      reduce genotyping cost and is useful in various applications, such as ancestry
      inference in association mapping, forensics and evolutionary theory in population
      genetics. Traditional methods to ascertain ancestral informative markers usually
      require the prior knowledge of individual ancestry and have difficulty for
      admixed populations. Recently Principal Components Analysis (PCA) has been
      employed with success to select SNPs which are highly correlated with top
      significant principal components (PCs) without use of individual ancestral
      information. The approach is also applicable to admixed populations. Here we
      propose a novel approach based on our recent result on summarizing population
      structure by graph laplacian eigenfunctions, which differs from PCA in that it is
      geometric and robust to outliers. Our approach also takes advantage of the priori
      sparseness of informative markers in the genome. Through simulation of a ring
      population and the real global population sample HGDP of 650K SNPs genotyped in
      940 unrelated individuals, we validate the proposed algorithm at selecting most
      informative markers, a small fraction of which can recover the similar underlying
      population structure efficiently. Employing a standard Support Vector Machine
      (SVM) to predict individuals' continental memberships on HGDP dataset of seven
      continents, we demonstrate that the selected SNPs by our method are more
      informative but less redundant than those selected by PCA. Our algorithm is a
      promising tool in genome-wide association studies and population genetics,
      facilitating the selection of structure informative markers, efficient detection
      of population substructure and ancestral inference.

PMID- 21079798
TI  - A new leptoceratopsid (Ornithischia: Ceratopsia) from the Upper Cretaceous of
      Shandong, China and its implications for neoceratopsian evolution.
AB  - BACKGROUND: The ceratopsians represent one of the last dinosaurian radiations.
      Traditionally the only universally accepted speciose clade within the group was
      the Ceratopsidae. However, recent discoveries and phylogenetic analyses have led
      to the recognition of a new speciose clade, the Leptoceratopsidae, which is
      predominantly known from the Upper Cretaceous of North America.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we report a new leptoceratopsid taxon,
      Zhuchengceratops inexpectus gen. et sp. nov., based on a partial, articulated
      skeleton recovered from the Upper Cretaceous Wangshi Group of Zhucheng, Shandong
      Province, China. Although Zhuchengceratops is significantly different from other
      known leptoceratopsids, it is recovered as a derived member of the group by our
      phylogenetic analysis. Furthermore, Zhuchengceratops exhibits several features
      previously unknown in leptoceratopsids but seen in ceratopsids and their close
      relatives, suggesting that the distribution of morphological features within
      ceratopsians is more complex than previously realized. CONCLUSION/SIGNIFICANCE:
      The discovery of Zhuchengceratops increases both the taxonomic diversity and the
      morphological disparity of the Leptoceratopsidae, providing further support for
      the hypothesis that this clade represents a successful radiation of horned
      dinosaurs in parallel with the Ceratopsidae in the Late Cretaceous. This
      documents a surprising case of the coexistence and radiation of two closely
      related lineages with contrasting suites of jaw and dental features that probably
      reflect adaptation to different food resources.

PMID- 21079797
TI  - Anti-tumor effect in human lung cancer by a combination treatment of novel
      histone deacetylase inhibitors: SL142 or SL325 and retinoic acids.
AB  - Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause
      apoptosis with low toxicity thereby constituting a promising treatment for
      cancer. In this study, we investigated the anti-tumor activity in lung cancer
      cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors
      SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced
      more cell growth inhibition and cell death than the hydroxamic acid-based HDAC
      inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination
      treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325
      significantly induced more apoptosis and suppressed colony formation than the
      single use of either. The expression of the retinoic acid receptors RARalpha,
      RARbeta, RXRalpha and RXRbeta were unchanged with the treatment. However a
      luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of
      the retinoic acid responsible element (RARE) generated significant
      transcriptional activity after the combination treatment of retinoic acids and
      SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax
      expression and caspase-3 activity was increased after the combination treatment.
      These results suggest that the combination treatment of SL142 or SL325 with
      retinoic acids exerts significant anti-tumor activity and is a promising
      therapeutic candidate to treat human lung cancer.

PMID- 21079799
TI  - Differential volatile signatures from skin, naevi and melanoma: a novel approach
      to detect a pathological process.
AB  - BACKGROUND: Early detection of melanoma is of great importance to reduce
      mortality. Discovering new melanoma biomarkers would improve early detection and
      diagnosis. Here, we present a novel approach to detect volatile compounds from
      skin. METHODS AND FINDINGS: We used Head Space Solid Phase Micro-Extraction (HS
      SPME) and gas chromatography/mass spectrometry (GC/MS) to identify volatile
      signatures from melanoma, naevi and skin samples. We hypothesized that the
      metabolic state of tissue alters the profile of volatile compounds. Volatiles
      released from fresh biopsy tissue of melanoma and benign naevus were compared
      based on their difference in frequency distribution and their expression level.
      We also analyzed volatile profiles from frozen tissue, including skin and
      melanoma. CONCLUSIONS: Three volatiles, 4-methyl decane, dodecane and undecane
      were preferentially expressed in both fresh and frozen melanoma, indicating that
      they are candidate biomarkers. Twelve candidate biomarkers evaluated by fuzzy
      logic analysis of frozen samples distinguished melanoma from skin with 89%
      sensitivity and 90% specificity. Our results demonstrate proof-of-principle that
      there is differential expression of volatiles in melanoma. Our volatile
      metabolomic approach will lead to a better understanding of melanoma and can
      enable development of new diagnostic and treatment strategies based on altered
      metabolism.

PMID- 21079800
TI  - Cortactin phosphorylated by ERK1/2 localizes to sites of dynamic actin regulation
      and is required for carcinoma lamellipodia persistence.
AB  - BACKGROUND: Tumor cell motility and invasion is governed by dynamic regulation of
      the cortical actin cytoskeleton. The actin-binding protein cortactin is commonly
      upregulated in multiple cancer types and is associated with increased cell
      migration. Cortactin regulates actin nucleation through the actin related protein
      (Arp)2/3 complex and stabilizes the cortical actin cytoskeleton. Cortactin is
      regulated by multiple phosphorylation events, including phosphorylation of S405
      and S418 by extracellular regulated kinases (ERK)1/2. ERK1/2 phosphorylation of
      cortactin has emerged as an important positive regulatory modification, enabling
      cortactin to bind and activate the Arp2/3 regulator neuronal Wiskott-Aldrich
      syndrome protein (N-WASp), promoting actin polymerization and enhancing tumor
      cell movement. METHODOLOGY/PRINCIPAL FINDINGS: In this report we have developed
      phosphorylation-specific antibodies against phosphorylated cortactin S405 and
      S418 to analyze the subcellular localization of this cortactin form in tumor
      cells and patient samples by microscopy. We evaluated the interplay between
      cortactin S405 and S418 phosphorylation with cortactin tyrosine phosphorylation
      in regulating cortactin conformational forms by Western blotting. Cortactin is
      simultaneously phosphorylated at S405/418 and Y421 in tumor cells, and through
      the use of point mutant constructs we determined that serine and tyrosine
      phosphorylation events lack any co-dependency. Expression of S405/418
      phosphorylation-null constructs impaired carcinoma motility and adhesion, and
      also inhibited lamellipodia persistence monitored by live cell imaging.
      CONCLUSIONS/SIGNIFICANCE: Cortactin phosphorylated at S405/418 is localized to
      sites of dynamic actin assembly in tumor cells. Concurrent phosphorylation of
      cortactin by ERK1/2 and tyrosine kinases enables cells with the ability to
      regulate actin dynamics through N-WASp and other effector proteins by
      synchronizing upstream regulatory pathways, confirming cortactin as an important
      integration point in actin-based signal transduction. Reduced lamellipodia
      persistence in cells with S405/418A expression identifies an essential motility
      based process reliant on ERK1/2 signaling, providing additional understanding as
      to how this pathway impacts tumor cell migration.

PMID- 21079801
TI  - POLD2 and KSP37 (FGFBP2) correlate strongly with histology, stage and outcome in
      ovarian carcinomas.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) constitutes more than 90% of ovarian
      cancers and is associated with high mortality. EOC comprises a heterogeneous
      group of tumours, and the causes and molecular pathology are essentially unknown.
      Improved insight into the molecular characteristics of the different subgroups of
      EOC is urgently needed, and should eventually lead to earlier diagnosis as well
      as more individualized and effective treatments. Previously, we reported a
      limited number of mRNAs strongly upregulated in human osteosarcomas and other
      malignancies, and six were selected to be tested for a possible association with
      three subgroups of ovarian carcinomas and clinical parameters.
      METHODOLOGY/PRINCIPAL FINDINGS: The six selected mRNAs were quantified by RT-qPCR
      in biopsies from eleven poorly differentiated serous carcinomas (PDSC, stage III
      IV), twelve moderately differentiated serous carcinomas (MDSC, stage III-IV) and
      eight clear cell carcinomas (CCC, stage I-IV) of the ovary. Superficial scrapings
      from six normal ovaries (SNO), as well as biopsies from three normal ovaries
      (BNO) and three benign ovarian cysts (BBOC) were analyzed for comparison. The
      gene expression level was related to the histological and clinical parameters of
      human ovarian carcinoma samples. One of the mRNAs, DNA polymerase delta 2 small
      subunit (POLD2), was increased in average 2.5- to almost 20-fold in MDSC and
      PDSC, respectively, paralleling the degree of dedifferentiation and concordant
      with a poor prognosis. Except for POLD2, the serous carcinomas showed a similar
      transcription profile, being clearly different from CCC. Another mRNA, Killer
      specific secretory protein of 37 kDa (KSP37) showed six- to eight-fold higher
      levels in CCC stage I compared with the more advanced staged carcinomas, and
      correlated positively with an improved clinical outcome.
      CONCLUSIONS/SIGNIFICANCE: We have identified two biomarkers which are markedly
      upregulated in two subgroups of ovarian carcinomas and are also associated with
      stage and outcome. The results suggest that POLD2 and KSP37 might be potential
      prognostic biomarkers.

PMID- 21079802
TI  - The mechanism of abrupt transition between theta and hyper-excitable spiking
      activity in medial entorhinal cortex layer II stellate cells.
AB  - Recent studies have shown that stellate cells (SCs) of the medial entorhinal
      cortex become hyper-excitable in animal models of temporal lobe epilepsy. These
      studies have also demonstrated the existence of recurrent connections among SCs,
      reduced levels of recurrent inhibition in epileptic networks as compared to
      control ones, and comparable levels of recurrent excitation among SCs in both
      network types. In this work, we investigate the biophysical and dynamic mechanism
      of generation of the fast time scale corresponding to hyper-excitable firing and
      the transition between theta and fast firing frequency activity in SCs. We show
      that recurrently connected minimal networks of SCs exhibit abrupt, threshold-like
      transition between theta and hyper-excitable firing frequencies as the result of
      small changes in the maximal synaptic (AMPAergic) conductance. The threshold
      required for this transition is modulated by synaptic inhibition. Similar abrupt
      transition between firing frequency regimes can be observed in single, self
      coupled SCs, which represent a network of recurrently coupled neurons
      synchronized in phase, but not in synaptically isolated SCs as the result of
      changes in the levels of the tonic drive. Using dynamical systems tools (phase
      space analysis), we explain the dynamic mechanism underlying the genesis of the
      fast time scale and the abrupt transition between firing frequency regimes, their
      dependence on the intrinsic SC's currents and synaptic excitation. This abrupt
      transition is mechanistically different from others observed in similar networks
      with different cell types. Most notably, there is no bistability involved. 'In
      vitro' experiments using single SCs self-coupled with dynamic clamp show the
      abrupt transition between firing frequency regimes, and demonstrate that our
      theoretical predictions are not an artifact of the model. In addition, these
      experiments show that high-frequency firing is burst-like with a duration
      modulated by an M-current.

PMID- 21079803
TI  - Safety, immunogenicity and duration of protection of the RTS,S/AS02(D) malaria
      vaccine: one year follow-up of a randomized controlled phase I/IIb trial.
AB  - BACKGROUND: The RTS,S/AS02(D) vaccine has been shown to have a promising safety
      profile, to be immunogenic and to confer protection against malaria in children
      and infants. METHODS AND FINDINGS: We did a randomized, controlled, phase I/IIb
      trial of RTS,S/AS02(D) given at 10, 14 and 18 weeks of age staggered with routine
      immunization vaccines in 214 Mozambican infants. The study was double-blind until
      the young child completed 6 months of follow-up over which period vaccine
      efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95%
      CI 42.6-79.8, p<0.0001). We now report safety, immunogenicity and estimated
      efficacy against clinical malaria up to 14 months after study start. Vaccine
      efficacy was assessed using Cox regression models. The frequency of serious
      adverse events was 32.7% in the RTS,S/AS02(D) and 31.8% in the control group. The
      geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to
      7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02(D), remaining 15
      fold higher than in the control group. Vaccine efficacy against clinical malaria
      was 33% (95% CI: -4.3-56.9, p = 0.076) over 14 months of follow-up. The hazard
      rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI
      35.1-88.2, p = 0.003). CONCLUSION: The RTS,S/AS02(D) malaria vaccine administered
      to young infants has a good safety profile and remains efficacious over 14
      months. A strong association between anti-CS antibodies and risk of clinical
      malaria has been described for the first time. The results also suggest a
      decrease of both anti-CS antibodies and vaccine efficacy over time. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00197028.

PMID- 21079804
TI  - Antioxidants protect keratinocytes against M. ulcerans mycolactone cytotoxicity.
AB  - BACKGROUND: Mycobacterium ulcerans is the causative agent of necrotizing skin
      ulcerations in distinctive geographical areas. M. ulcerans produces a macrolide
      toxin, mycolactone, which has been identified as an important virulence factor in
      ulcer formation. Mycolactone is cytotoxic to fibroblasts and adipocytes in vitro
      and has modulating activity on immune cell functions. The effect of mycolactone
      on keratinocytes has not been reported previously and the mechanism of
      mycolactone toxicity is presently unknown. Many other macrolide substances have
      cytotoxic and immunosuppressive activities and mediate some of their effects via
      production of reactive oxygen species (ROS). We have studied the effect of
      mycolactone in vitro on human keratinocytes--key cells in wound healing--and
      tested the hypothesis that the cytotoxic effect of mycolactone is mediated by
      ROS. METHODOLOGY/PRINCIPAL FINDINGS: The effect of mycolactone on primary skin
      keratinocyte growth and cell numbers was investigated in serum free growth medium
      in the presence of different antioxidants. A concentration and time dependent
      reduction in keratinocyte cell numbers was observed after exposure to
      mycolactone. Several different antioxidants inhibited this effect partly. The ROS
      inhibiting substance deferoxamine, which acts via chelation of Fe(2+), completely
      prevented mycolactone mediated cytotoxicity. CONCLUSIONS/SIGNIFICANCE: This study
      demonstrates that mycolactone mediated cytotoxicity can be inhibited by
      deferoxamine, suggesting a role of iron and ROS in mycolactone induced
      cytotoxicity of keratinocytes. The data provide a basis for the understanding of
      Buruli ulcer pathology and the development of improved therapies for this
      disease.

PMID- 21079805
TI  - In vitro HIV-1 selective integration into the target sequence and decoy-effect of
      the modified sequence.
AB  - Although there have been a few reports that the HIV-1 genome can be selectively
      integrated into the genomic DNA of cultured host cell, the biochemistry of
      integration selectivity has not been fully understood. We modified the in vitro
      integration reaction protocol and developed a reaction system with higher
      efficiency. We used a substrate repeat, 5'-(GTCCCTTCCCAGT)(n)(ACTGGGAAGGGAC)(n)
      3', and a modified sequence DNA ligated into a circular plasmid. CAGT and ACTG
      (shown in italics in the above sequence) in the repeat units originated from the
      HIV-1 proviral genome ends. Following the incubation of the HIV-1 genome end cDNA
      and recombinant integrase for the formation of the pre-integration (PI) complex,
      substrate DNA was reacted with this complex. It was confirmed that the
      integration selectively occurred in the middle segment of the repeat sequence. In
      addition, integration frequency and selectivity were positively correlated with
      repeat number n. On the other hand, both frequency and selectivity decreased
      markedly when using sequences with deletion of CAGT in the middle position of the
      original target sequence. Moreover, on incubation with the deleted DNAs and
      original sequence, the integration efficiency and selectivity for the original
      target sequence were significantly reduced, which indicated interference effects
      by the deleted sequence DNAs. Efficiency and selectivity were also found to vary
      discontinuously with changes in manganese dichloride concentration in the
      reaction buffer, probably due to its influence on the secondary structure of
      substrate DNA. Finally, integrase was found to form oligomers on the binding site
      and substrate DNA formed a loop-like structure. In conclusion, there is a
      considerable selectivity in HIV-integration into the specified sequence; however,
      similar DNA sequences can interfere with the integration process, and it is
      therefore difficult for in vivo integration to occur selectively in the actual
      host genome DNA.

PMID- 21079806
TI  - Two-photon imaging of calcium in virally transfected striate cortical neurons of
      behaving monkey.
AB  - Two-photon scanning microscopy has advanced our understanding of neural signaling
      in non-mammalian species and mammals. Various developments are needed to perform
      two-photon scanning microscopy over prolonged periods in non-human primates
      performing a behavioral task. In striate cortex in two macaque monkeys, cortical
      neurons were transfected with a genetically encoded fluorescent calcium sensor,
      memTNXL, using AAV1 as a viral vector. By constructing an extremely rigid and
      stable apparatus holding both the two-photon scanning microscope and the monkey's
      head, single neurons were imaged at high magnification for prolonged periods with
      minimal motion artifacts for up to ten months. Structural images of single
      neurons were obtained at high magnification. Changes in calcium during visual
      stimulation were measured as the monkeys performed a fixation task. Overall,
      functional responses and orientation tuning curves were obtained in 18.8% of the
      234 labeled and imaged neurons. This demonstrated that the two-photon scanning
      microscopy can be successfully obtained in behaving primates.

PMID- 21079807
TI  - BK channels mediate cholinergic inhibition of high frequency cochlear hair cells.
AB  - BACKGROUND: Outer hair cells are the specialized sensory cells that empower the
      mammalian hearing organ, the cochlea, with its remarkable sensitivity and
      frequency selectivity. Sound-evoked receptor potentials in outer hair cells are
      shaped by both voltage-gated K(+) channels that control the membrane potential
      and also ligand-gated K(+) channels involved in the cholinergic efferent
      modulation of the membrane potential. The objectives of this study were to
      investigate the tonotopic contribution of BK channels to voltage- and ligand
      gated currents in mature outer hair cells from the rat cochlea.
      METHODOLOGY/PRINCIPAL: Findings In this work we used patch clamp
      electrophysiology and immunofluorescence in tonotopically defined segments of the
      rat cochlea to determine the contribution of BK channels to voltage- and ligand
      gated currents in outer hair cells. Although voltage and ligand-gated currents
      have been investigated previously in hair cells from the rat cochlea, little is
      known about their tonotopic distribution or potential contribution to efferent
      inhibition. We found that apical (low frequency) outer hair cells had no BK
      channel immunoreactivity and little or no BK current. In marked contrast, basal
      (high frequency) outer hair cells had abundant BK channel immunoreactivity and BK
      currents contributed significantly to both voltage-gated and ACh-evoked K(+)
      currents. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that basal (high
      frequency) outer hair cells may employ an alternative mechanism of efferent
      inhibition mediated by BK channels instead of SK2 channels. Thus, efferent
      synapses may use different mechanisms of action both developmentally and
      tonotopically to support high frequency audition. High frequency audition has
      required various functional specializations of the mammalian cochlea, and as
      shown in our work, may include the utilization of BK channels at efferent
      synapses. This mechanism of efferent inhibition may be related to the unique
      acetylcholine receptors that have evolved in mammalian hair cells compared to
      those of other vertebrates.

PMID- 21079808
TI  - HiNO: an approach for inferring hierarchical organization from regulatory
      networks.
AB  - BACKGROUND: Gene expression as governed by the interplay of the components of
      regulatory networks is indeed one of the most complex fundamental processes in
      biological systems. Although several methods have been published to unravel the
      hierarchical structure of regulatory networks, weaknesses such as the incorrect
      or inconsistent assignment of elements to their hierarchical levels, the
      incapability to cope with cyclic dependencies within the networks or the need for
      a manual curation to retrieve non-overlapping levels remain unsolved.
      METHODOLOGY/RESULTS: We developed HiNO as a significant improvement of the so
      called breadth-first-search (BFS) method. While BFS is capable of determining the
      overall hierarchical structures from gene regulatory networks, it especially has
      problems solving feed-forward type of loops leading to conflicts within the level
      assignments. We resolved these problems by adding a recursive correction approach
      consisting of two steps. First each vertex is placed on the lowest level that
      this vertex and its regulating vertices are assigned to (downgrade procedure).
      Second, vertices are assigned to the next higher level (upgrade procedure) if
      they have successors with the same level assignment and have themselves no
      regulators. We evaluated HiNO by comparing it with the BFS method by applying
      them to the regulatory networks from Saccharomyces cerevisiae and Escherichia
      coli, respectively. The comparison shows clearly how conflicts in level
      assignment are resolved in HiNO in order to produce correct hierarchical
      structures even on the local levels in an automated fashion. CONCLUSIONS: We
      showed that the resolution of conflicting assignments clearly improves the BFS
      method. While we restricted our analysis to gene regulatory networks, our
      approach is suitable to deal with any directed hierarchical networks structure
      such as the interaction of microRNAs or the action of non-coding RNAs in general.
      Furthermore we provide a user-friendly web-interface for HiNO that enables the
      extraction of the hierarchical structure of any directed regulatory network.
      AVAILABILITY: HiNO is freely accessible at http://mips.helmholtz
      muenchen.de/hino/.

PMID- 21079809
TI  - Quantifying child mortality reductions related to measles vaccination.
AB  - BACKGROUND: This study characterizes the historical relationship between coverage
      of measles containing vaccines (MCV) and mortality in children under 5 years,
      with a view toward ongoing global efforts to reduce child mortality.
      METHODOLOGY/PRINCIPAL FINDINGS: Using country-level, longitudinal panel data,
      from 44 countries over the period 1960-2005, we analyzed the relationship between
      MCV coverage and measles mortality with (1) logistic regressions for no measles
      deaths in a country-year, and (2) linear regressions for the logarithm of the
      measles death rate. All regressions allowed a flexible, non-linear relationship
      between coverage and mortality. Covariates included birth rate, death rates from
      other causes, percent living in urban areas, population density, per-capita GDP,
      use of the two-dose MCV, year, and mortality coding system. Regressions used
      lagged covariates, country fixed effects, and robust standard errors clustered by
      country. The likelihood of no measles deaths increased nonlinearly with higher
      MCV coverage (ORs: 13.8 [1.6-122.7] for 80-89% to 40.7 [3.2-517.6] for >=95%),
      compared to pre-vaccination risk levels. Measles death rates declined nonlinearly
      with higher MCV coverage, with benefits accruing more slowly above 90% coverage.
      Compared to no coverage, predicted average reductions in death rates were -79% at
      70% coverage, -93% at 90%, and -95% at 95%. CONCLUSIONS/SIGNIFICANCE: 40 years of
      experience with MCV vaccination suggests that extremely high levels of
      vaccination coverage are needed to produce sharp reductions in measles deaths.
      Achieving sustainable benefits likely requires a combination of extended vaccine
      programs and supplementary vaccine efforts.

PMID- 21079810
TI  - Efficient simulation of the spatial transmission dynamics of influenza.
AB  - Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies
      over-estimated the within-country rate of spatial spread of pandemic influenza.
      As large spatially resolved data sets are constructed, the need for efficient
      simulation code with which to investigate the spatial patterns of the pandemic
      becomes clear. Here, we present a significant improvement to the efficiency of an
      individual-based stochastic disease simulation framework commonly used in
      multiple previous studies. We quantify the efficiency of the revised algorithm
      and present an alternative parameterization of the model in terms of the basic
      reproductive number. We apply the model to the population of Taiwan and
      demonstrate how the location of the initial seed can influence spatial incidence
      profiles and the overall spread of the epidemic. Differences in incidence are
      driven by the relative connectivity of alternate seed locations. The ability to
      perform efficient simulation allows us to run a batch of simulations and take
      account of their average in real time. The averaged data are stable and can be
      used to differentiate spreading patterns that are not readily seen by only
      conducting a few runs.

PMID- 21079811
TI  - ER-alpha36, a novel variant of ER-alpha, mediates estrogen-stimulated
      proliferation of endometrial carcinoma cells via the PKCdelta/ERK pathway.
AB  - BACKGROUND: Recently, a variant of ER-alpha, ER-alpha36 was identified and
      cloned. ER-alpha36 lacks intrinsic transcription activity and mainly mediates non
      genomic estrogen signaling. The purpose of this study was to investigate the
      function and the underlying mechanisms of ER-alpha36 in growth regulation of
      endometrial Ishikawa cancer cells. METHODS: The cellular localization of ER
      alpha36 and ER-alpha66 were determined by immunofluorescence in the Ishikawa
      cells. Ishikawa endometrial cancer control cells transfected with an empty
      expression vector, Ishikawa cells with shRNA knockdown of ER-alpha36
      (Ishikawa/RNAiER36) and Ishikawa cells with shRNA knockdown of ER-alpha66
      (Ishikawa/RNAiER66) were treated with E2 and E2-conjugated to bovine serum
      albumin (E2-BSA, membrane impermeable) in the absence and presence of different
      kinase inhibitors HBDDE, bisindolylmaleimide, rottlerin, H89 and U0126. The
      phosphorylation levels of signaling molecules and cyclin D1/cdk4 expression were
      examined with Western blot analysis and cell growth was monitored with the MTT
      assay. RESULTS: Immunofluorescence staining of Ishikawa cells demonstrated that
      ER-alpha36 was expressed mainly on the plasma membrane and in the cytoplasm,
      while ER-alpha66 was predominantly localized in the cell nucleus. Both E2 and E2
      BSA rapidly activated PKCdelta not PKCalpha in Ishikawa cells, which could be
      abrogated by ER-alpha36 shRNA expression. E2-and E2-BSA-induced ERK
      phosphorylation required ER-alpha36 and PKCdelta. However, only E2 was able to
      induce Camp-dependent protein kinase A (PKA) phosphorylation. Furthermore, E2
      enhances cyclin D1/cdk4 expression via ER-alpha36. CONCLUSION: E2 activates the
      PKCdelta/ERK pathway and enhances cyclin D1/cdk4 expression via the membrane
      initiated signaling pathways mediated by ER-alpha36, suggesting a possible
      involvement of ER-alpha36 in E2-dependent growth-promoting effects in endometrial
      cancer cells.

PMID- 21079812
TI  - TXNL6 is a novel oxidative stress-induced reducing system for methionine
      sulfoxide reductase a repair of alpha-crystallin and cytochrome C in the eye
      lens.
AB  - A key feature of many age-related diseases is the oxidative stress-induced
      accumulation of protein methionine sulfoxide (PMSO) which causes lost protein
      function and cell death. Proteins whose functions are lost upon PMSO formation
      can be repaired by the enzyme methionine sulfoxide reductase A (MsrA) which is a
      key regulator of longevity. One disease intimately associated with PMSO formation
      and loss of MsrA activity is age-related human cataract. PMSO levels increase in
      the eye lens upon aging and in age-related human cataract as much as 70% of total
      lens protein is converted to PMSO. MsrA is required for lens cell maintenance,
      defense against oxidative stress damage, mitochondrial function and prevention of
      lens cataract formation. Essential for MsrA action in the lens and other tissues
      is the availability of a reducing system sufficient to catalytically regenerate
      active MsrA. To date, the lens reducing system(s) required for MsrA activity has
      not been defined. Here, we provide evidence that a novel thioredoxin-like protein
      called thioredoxin-like 6 (TXNL6) can serve as a reducing system for MsrA repair
      of the essential lens chaperone alpha-crystallin/sHSP and mitochondrial
      cytochrome c. We also show that TXNL6 is induced at high levels in human lens
      epithelial cells exposed to H(2)O(2)-induced oxidative stress. Collectively,
      these data suggest a critical role for TXNL6 in MsrA repair of essential lens
      proteins under oxidative stress conditions and that TXNL6 is important for MsrA
      defense protection against cataract. They also suggest that MsrA uses multiple
      reducing systems for its repair activity that may augment its function under
      different cellular conditions.

PMID- 21079813
TI  - Breeding experience and the heritability of female mate choice in collared
      flycatchers.
AB  - BACKGROUND: Heritability in mate preferences is assumed by models of sexual
      selection, and preference evolution may contribute to adaptation to changing
      environments. However, mate preference is difficult to measure in natural
      populations as detailed data on mate availability and mate sampling are usually
      missing. Often the only available information is the ornamentation of the actual
      mate. The single long-term quantitative genetic study of a wild population found
      low heritability in female mate ornamentation in Swedish collared flycatchers.
      One potentially important cause of low heritability in mate ornamentation at the
      population level is reduced mate preference expression among inexperienced
      individuals. METHODOLOGY/PRINCIPAL FINDINGS: Applying animal model analyses to 21
      years of data from a Hungarian collared flycatcher population, we found that
      additive genetic variance was 50 percent and significant for ornament expression
      in males, but less than 5 percent and non-significant for mate ornamentation
      treated as a female trait. Female breeding experience predicted breeding date and
      clutch size, but mate ornamentation and its variance components were unrelated to
      experience. Although we detected significant area and year effects on mate
      ornamentation, more than 85 percent of variance in this trait remained
      unexplained. Moreover, the effects of area and year on mate ornamentation were
      also highly positively correlated between inexperienced and experienced females,
      thereby acting to remove difference between the two groups.
      CONCLUSIONS/SIGNIFICANCE: The low heritability of mate ornamentation was
      apparently not explained by the presence of inexperienced individuals. Our
      results further indicate that the expression of mate ornamentation is dominated
      by temporal and spatial constraints and unmeasured background factors. Future
      studies should reduce unexplained variance or use alternative measures of mate
      preference. The heritability of mate preference in the wild remains a principal
      but unresolved question in evolutionary ecology.

PMID- 21079815
TI  - Changes to euchromatin on LAT and ICP4 following reactivation are more prevalent
      in an efficiently reactivating strain of HSV-1.
AB  - BACKGROUND: Epigenetic mechanisms, via post-translational histone modifications,
      have roles in the establishment and maintenance of latency of the HSV-1 genome in
      the sensory neurons. Considering that many post-translational histone marks are
      reversible in nature, epigenetic mechanisms may also play a critical role in the
      process of induced HSV-1 reactivation. METHODOLOGY/PRINCIPAL FINDINGS: This study
      utilized the rabbit ocular model of HSV-1 infection and reactivation, induced by
      the transcorneal iontophoresis of epinephrine (TCIE), to characterize changes to
      chromatin that occur between 0.5 and 4 h following the application of the
      reactivation stimulus. Our goal was to explore the hypothesis that chromatin
      remodeling is an early and essential step in the process of HSV-1 reactivation.
      Analysis of the HSV-1 latently infected rabbit trigeminal ganglia (TG) showed
      that enrichment of the euchromatic marker H3K4me2 significantly decreased in the
      LAT 5'exon region (~2.5-fold) and significantly increased in the lytic ICP4
      promoter region (~3-fold) by 1 h post-TCIE in the highly efficient reactivating
      McKrae strain of HSV-1. In contrast, we observed no significant change in the
      euchromatic marks of H3K4me2 associated with LAT 5'exon or ICP4 promoter regions
      of the poorly reactivating KOS strain of HSV-1 following TCIE through 4 h. The
      implication that these observed epigenetic changes were linked to transcriptional
      activity was confirmed by qRT-PCR examining both LAT and lytic transcript
      abundance following TCIE. We found a significant decrease in the abundance of LAT
      RNA by 2 h post-iontophoresis of epinephrine coupled to an increase in the
      transcript abundance of ICP4 in the McKrae strain of HSV-1. By comparison, we
      observed no change in the LAT or ICP4 transcript abundance of the poor
      reactivator KOS following iontophoresis of epinephrine through 4 h.
      CONCLUSIONS/SIGNIFICANCE: Our results implicate that chromatin remodeling is an
      early and essential step involved in the process of in vivo HSV-1 reactivation.

PMID- 21079814
TI  - On the role of the striatum in response inhibition.
AB  - BACKGROUND: Stopping a manual response requires suppression of the primary motor
      cortex (M1) and has been linked to activation of the striatum. Here, we test
      three hypotheses regarding the role of the striatum in stopping: striatum
      activation during successful stopping may reflect suppression of M1, anticipation
      of a stop-signal occurring, or a slower response build-up. METHODOLOGY/PRINCIPAL
      FINDINGS: Twenty-four healthy volunteers underwent functional magnetic resonance
      imaging (fMRI) while performing a stop-signal paradigm, in which anticipation of
      stopping was manipulated using a visual cue indicating stop-signal probability,
      with their right hand. We observed activation of the striatum and deactivation of
      left M1 during successful versus unsuccessful stopping. In addition, striatum
      activation was proportional to the degree of left M1 deactivation during
      successful stopping, implicating the striatum in response suppression.
      Furthermore, striatum activation increased as a function of stop-signal
      probability and was to linked to activation in the supplementary motor complex
      (SMC) and right inferior frontal cortex (rIFC) during successful stopping,
      suggesting a role in anticipation of stopping. Finally, trial-to-trial variations
      in response time did not affect striatum activation. CONCLUSIONS/SIGNIFICANCE:
      The results identify the striatum as a critical node in the neural network
      associated with stopping motor responses. As striatum activation was related to
      both suppression of M1 and anticipation of a stop-signal occurring, these
      findings suggest that the striatum is involved in proactive inhibitory control
      over M1, most likely in interaction with SMC and rIFC.

PMID- 21079817
TI  - Liver mitochondria and insulin resistance.
AB  - With a steadily increasing prevalence, insulin resistance (IR) is a major public
      health issue. This syndrome is defined as a set of metabolic dysfunctions
      associated with, or contributing to, a range of serious health problems. These
      disorders include type 2 diabetes, metabolic syndrome, obesity, and non-alcoholic
      steatohepatitis (NASH). According to the literature in the field, several cell
      types like beta-cell, myocyte, hepatocyte and/or adipocyte, as well as related
      complex signaling environment involved in peripheral insulin sensitivity are
      believed to be central in this pathology. Because of the central role of the
      liver in the whole-body energy homeostasis, liver insulin sensitivity and its
      potential relationship with mitochondrial oxidative phosphorylation appear to be
      crucial. The following short review highlights how liver mitochondria could be
      implicated in IR and should therefore be considered as a specific therapeutic
      target in the future.

PMID- 21079816
TI  - Evaluation of the association between the AC3 genetic polymorphisms and obesity
      in a Chinese Han population.
AB  - BACKGROUND: AC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin
      signaling pathway. Recent reports have demonstrated that the AC3 genetic
      polymorphisms are associated with obesity in a Swedish population. AC3 knock out
      mice exhibit obese when they age. These findings suggest that AC3 plays an
      important role in the regulation of body weight. METHODOLOGY/PRINCIPAL FINDINGS:
      In the present study, we evaluated the association between the AC3 genetic
      polymorphisms and obesity in a Han Chinese population. A total of 2580 adults,
      including 1490 lean (BMI = 18.5-23.9), 677 overweight (BMI 24.0-27.9) and 413
      obese (BMI >=28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single
      maker association analyses indicated that SNP rs753529 was significantly
      associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623
      0.963), but not in overweight subjects (P = 0.818). Multiple maker association
      analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568,
      rs7604576 and rs753529 was significantly associated with obesity (P = 0.029).
      Further genotyping of SNP rs753529 in 816 children, including 361 overweight
      subjects (BMI>P(80)) and 455 controls (BMI = P(20-50)) were performed, and no
      significant association with BMI was found. All tests were adjusted for age, sex,
      physical activity index, household income and/or diet expenses. CONCLUSIONS: The
      present study provides replication evidence that the AC3 genetic polymorphisms
      are associated with decreased risk of obesity among adults but not in children in
      a Chinese Han population. The data also suggest that the AC3 genetic effects on
      BMI may have interaction with the factors related to ageing and environment.

PMID- 21079818
TI  - Atorvastatin improves tubular status in non-diabetic patients with chronic kidney
      disease - placebo controlled, randomized, cross-over study.
AB  - BACKGROUND: There is evidence that dyslipidemia is associated with chronic kidney
      disease (CKD) and it has been implicated in the progression of renal damage.
      Optimal management of dyslipidemia should therefore lead to renal benefits. A
      number of experimental models demonstrate a beneficial effect of statins in
      ameliorating renal damage. However, the exact mechanism by which statins protect
      against renal damage remains unclear. METHODS: In a placebo-controlled,
      randomized, cross-over study we evaluated the influence of atorvastatin (ATO) 40
      mg/day added to the renin-angiotensin-aldosterone systeme (RAAS) blockade on
      proteinuria and surrogate biomarkers of tubular damage or injury in 14 non
      diabetic patients with proteinuria (0.4-1.8 g per 24 h) with normal or declined
      kidney function (eGFR 55-153 ml/min). In the eight-week run-in period, therapy
      using angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II
      subtype 1 receptor antagonists (ARB) was adjusted to achieve a blood pressure
      below 130/80 mm Hg. Next, patients were randomly assigned to one of two treatment
      sequences: ATO/washout/placebo or placebo/washout/ATO. Clinical evaluation and
      laboratory tests were performed at the randomization point and after each period
      of the study. The primary end point of this study was a change in proteinuria
      measured as 24-h urine protein excretion (DPE). Secondary end points included
      urine N-acetyl-beta-D-glucosaminidase (NAG) and alpha1-microglobulin (alpha1m)
      excretion. RESULTS: The ATO therapy significantly reduced urine excretion of
      alpha1m (p=0.033) and NAG (p=0.038) as compared to placebo. There were no
      differences in proteinuria, blood pressure, eGFR and serum creatinine between the
      ATO and placebo groups. CONCLUSION: Atorvastatin treatment is safe and improves
      biomarkers of tubular damage or injury in non-diabetic patients with CKD.

PMID- 21079819
TI  - Expression, purification and functional characterization of recombinant human
      acyl-CoA-binding protein (ACBP) from erythroid cells.
AB  - Fatty acyl-CoA esters are extremely important in cellular homeostasis. They are
      intermediates in both lipid metabolism and post-translational protein
      modifications. Among these modification events, protein palmitoylation seems to
      be unique by its reversibility which allows dynamic regulation of the protein
      hydrophobicity. The recent discovery of an enzyme family that catalyze protein
      palmitoylation has increased the understanding of the enzymology of the covalent
      attachment of fatty acids to proteins. Despite that, the molecular mechanism of
      supplying acyl-CoA esters to this reaction is yet to be established. Acyl
      coenzyme A-binding proteins are known to bind long-chain acyl-CoA esters with
      very high affinity. Therefore, they play a significant role in intracellular acyl
      CoA transport and pool formation. The purpose of this work is to explore the
      potential of one of the acyl-CoA-binding proteins to participate in the protein
      palmitoylation. In this study, a recombinant form of ACBP derived from human
      erythroid cells was expressed in E. coli, purified, and functionally
      characterized. We demonstrate that recombinant hACBP effectively binds palmitoyl
      CoA in vitro, undergoing a shift from a monomeric to a dimeric state, and that
      this ligand-binding ability is involved in erythrocytic membrane
      phosphatidylcholine (PC) remodeling but not in protein acylation.

PMID- 21079820
TI  - Insight into carbon nanotube effect on polymer molecular orientation: an infrared
      dichroism study.
AB  - The effect of carbon nanotubes on polymer macromolecular orientation structure
      during stretching of syndiotactic polystyrene/carbon nanotube nanocomposite film
      was quantitatively studied for the first time by an infrared dichroism technique.

PMID- 21079821
TI  - Re(V) and Re(III) complexes with sal2phen and triphenylphosphine: rearrangement,
      oxidation and reduction.
AB  - Reactions of Re(V), tetradentate Schiff base complexes with tertiary phosphines
      have previously yielded both rearranged Re(V) and reduced Re(III) complexes. To
      further understand this chemistry, the rigid diiminediphenol (N(2)O(2)) Schiff
      base ligand sal(2)phen (N,N'-o-phenylenebis(salicylaldimine)) was reacted with (n
      Bu(4)N)[ReOCl(4)] to yield trans-[ReOCl(sal(2)phen)] (1). On reaction with
      triphenylphosphine (PPh(3)), a rearranged Re(V) product cis
      [ReO(PPh(3))(sal(2)phen*)]PF(6) (2), in which one of the imines was reduced to an
      amine during the reaction, and the reduced Re(III) products trans
      [ReCl(PPh(3))(sal(2)phen)] (4) and trans-[Re(PPh(3))(2)(sal(2)phen)](+) (5) were
      isolated. Reaction of sal(2)phen with [ReCl(3)(PPh(3))(2)(CH(3)CN)] resulted in
      the isolation of [ReCl(2)(PPh(3))(2)(salphen)] (3). The compounds were
      characterized using standard spectroscopic methods, elemental analyses and single
      crystal X-ray crystallography.

PMID- 21079822
TI  - On the electron-induced isotope fractionation in low temperature
      (32)O(2)/(36)O(2) ices--ozone as a case study.
AB  - The formation of six ozone isotopomers and isotopologues, (16)O(16)O(16)O,
      (18)O(18)O(18)O, (16)O(16)O(18)O, (18)O(18)O(16)O, (16)O(18)O(16)O, and
      (18)O(16)O(18)O, has been studied in electron-irradiated solid oxygen (16)O(2)
      and (18)O(2) (1 ? 1) ices at 11 K. Significant isotope effects were found to
      exist which involved enrichment of (18)O-bearing ozone molecules. The heavy
      (18)O(18)O(18)O species is formed with a factor of about six higher than the
      corresponding (16)O(16)O(16)O isotopologue. Likewise, the heavy (18)O(18)O(16)O
      species is formed with abundances of a factor of three higher than the lighter
      (16)O(16)O(18)O counterpart. No isotope effect was observed in the production of
      (16)O(18)O(16)O versus(18)O(16)O(18)O. Such studies on the formation of distinct
      ozone isotopomers and isotopologues involving non-thermal, non-equilibrium
      chemistry by irradiation of oxygen ices with high energy electrons, as present in
      the magnetosphere of the giant planets Jupiter and Saturn, may suggest that
      similar mechanisms may contribute to the (18)O enrichment on the icy satellites
      of Jupiter and Saturn such as Ganymede, Rhea, and Dione. In such a Solar System
      environment, energetic particles from the magnetospheres of the giant planets may
      induce non-equilibrium reactions of suprathermal and/or electronically excited
      atoms under conditions, which are quite distinct from isotopic enrichments found
      in classical, thermal gas phase reactions.

PMID- 21079823
TI  - The importance of ion size and electrode curvature on electrical double layers in
      ionic liquids.
AB  - Room-temperature ionic liquids (ILs) are an emerging class of electrolytes for
      supercapacitors. We investigate the effects of ion size and electrode curvature
      on the electrical double layers (EDLs) in two ILs 1-butyl-3-methylimidazolium
      chloride [BMIM][Cl] and 1-butyl-3-methylimidazolium hexafluorophosphate
      [BMIM][PF(6)], using a combination of molecular dynamics (MD) and quantum density
      functional theory (DFT) simulations. The sizes of the counter-ion and co-ion
      affect the ion distribution and orientational structure of EDLs. The EDL
      capacitances near both planar and cylindrical electrodes were found to follow the
      order: [BMIM][Cl] (near the positive electrode) > [BMIM][PF(6)] (near the
      positive electrode) ~ [BMIM][Cl] (near the negative electrode) ~ [BMIM][PF(6)]
      (near the negative electrode). The EDL capacitance was also found to increase as
      the electrode curvature increases. These capacitance data can be fit to the
      Helmholtz model and the recently proposed exohedral electrical double-cylinder
      capacitor (xEDCC) model when the EDL thickness is properly parameterized, even
      though key features of the EDLs in ILs are not accounted for in these models. To
      remedy the shortcomings of existing models, we propose a "Multiple Ion Layers
      with Overscreening" (MILO) model for the EDLs in ILs that takes into account two
      critical features of such EDLs, i.e., alternating layering of counter-ions and co
      ions and charge overscreening. The capacitance computed from the MILO model
      agrees well with the MD prediction. Although some input parameters of the MILO
      model must be obtained from MD simulations, the MILO model may provide a new
      framework for understanding many important aspects of EDLs in ILs (e.g., the
      variation of EDL capacitance with the electrode potential) that are difficult to
      interpret using classical EDL models and experiments.

PMID- 21079824
TI  - ZnO nanocone: application in fabrication of the smallest whispering gallery
      optical resonator.
AB  - ZnO semiconductors at the micro- and nanometre scales are attractive in optical,
      magnetic, and electronic applications because of their particular features and
      excellent properties. The whispering gallery mode (WGM) is a general and
      effective type to amplify the intensity of the luminescence emission, and has
      gained extensive application in lasing and microcavities. In this contribution,
      we reported that the smallest whispering gallery optical resonator has been
      achieved in an individual ZnO nanocone whose diameter gradually reduces from
      bottom to top in the range of 700 to 50 nm. Using the monochromatic
      cathodoluminescence (CL) equipment attached at a scanning electron microscopy, we
      observed the alternating patterns of bright and dark rings from the monochromatic
      CL image of an individual ZnO nanocone, which is attributed to the WGM-like
      enhanced luminescence emission when the ZnO nanocone is considered as an optical
      resonator. The smallest mode number of WGM, N=0, was observed in the ZnO nanocone
      with a radius of 55 nm for the considered light wavelength of 380 nm, and with a
      radius of 81 nm for the considered light wavelength of 500 nm, respectively.
      These results showed that the smallest whispering gallery optical resonator from
      an individual ZnO nanocone has been fabricated. Experiments are in good agreement
      with both theoretical predictions and computer simulations based on the finite
      difference time domain method with perfectly matched layer boundary conditions.
      These findings provided valuable information for applications of ZnO micro- and
      nanostructures in optoelectronic devices.

PMID- 21079825
TI  - Direct conversion of urea into graphitic carbon nitride over mesoporous TiO2
      spheres under mild condition.
AB  - Mesoporous TiO(2) spheres with a large surface area and rich surface hydroxyl
      groups have been prepared through a light-driven synthetic strategy, and the as
      prepared mesoporous material is able to convert urea to carbon nitride
      efficiently under a mild condition.

PMID- 21079826
TI  - Preparation of carbon quantum dots with tunable photoluminescence by rapid laser
      passivation in ordinary organic solvents.
AB  - A simple approach to prepare carbon quantum dots is presented in this
      communication by laser rapid passivation of nano carbon particles in ordinary
      organic solvent. The as-prepared carbon dots exhibited visible, tunable and
      stable photoluminescence (PL). XPS analysis showed that the increased oxygen
      concentration might be concerned with the origin of PL.

PMID- 21079827
TI  - Fluorescent nanoparticles assembled from a poly(ionic liquid) for selective
      sensing of copper ions.
AB  - Fluorescent nanoparticles were formed from a poly(ionic liquid) through ion
      interactions. The fluorescent nanoparticles show highly fluorescent intensity and
      stability to UV light irradiation and were utilized for highly sensitive and
      selectivity fluorescent sensor of copper ion.

PMID- 21079828
TI  - Improved photovoltaic performance of P3HT:PCBM cells by addition of a low band
      gap oligomer.
AB  - The introduction of a low band-gap oligomer, oligo(benzo[1,2,5]thiadiazole-alt
      3,3'''-dihexylquaterthiophene) (BT4T) improved the performance of P3HT:PCBM bulk
      heterojunction organic photovoltaic cells due to improved UV-vis absorption and
      increased P3HT crystallinity.

PMID- 21079829
TI  - Preparation of benzolactams by Pd(II)-catalyzed carbonylation of N-unprotected
      arylethylamines.
AB  - An unprecedented NH(2)-directed Pd(II)-catalytic carbonylation of quaternary
      aromatic alpha-amino esters to yield 6-membered benzolactams has been developed.
      The reaction shows a strong bias to 6-membered lactams over 5-membered ones. The
      steric hindrance around the amino group seems to be pivotal for the success of
      the process.

PMID- 21079830
TI  - Alloyed (ZnS)(x)(Cu2SnS3)(1-x) and (CuInS2)(x)(Cu2SnS3)(1-x) nanocrystals with
      arbitrary composition and broad tunable band gaps.
AB  - Cu(2)SnS(3) nanocrystals with metastable zincblende and wurtzite structures have
      been successfully synthesized for the first time. Alloyed (ZnS)(x)(Cu(2)SnS(3))(1
      x) and (CuInS(2))(x)(Cu(2)SnS(3))(1-x) nanocrystals with arbitrary composition (0
      <=x<= 1) and ultra-broad tunable band gaps (3.63 to 0.94 eV) were obtained.

PMID- 21079831
TI  - Development of chiral N,N-ditopic metalloligands based on a Cinchona alkaloids'
      backbone for constructing homochiral coordination polymers.
AB  - The bimetallic chiral bipyridyl-type metalloligands based on aluminium
      derivatives of cinchonine, [R(2)Al(MU-CN)](2) (R = Me or Et), in combination with
      the corresponding ZnR(2) compound as nodes were used for the generation of novel
      homochiral heterometallic coordination polymers of either zig-zag or helical
      topology, depending on the character of the R substituent.

PMID- 21079832
TI  - Designed synthesis of TS-1 crystals with controllable b-oriented length.
AB  - TS-1 crystals with controllable b-oriented length (sheet-like morphology, TS-1-S;
      chain-like morphology, TS-1-C) have been rationally synthesized from addition of
      organic additives (urea and fluorinated surfactant of FC-4) in the starting
      titanosilicate gels, and catalytic and adsorptive measurements show that TS-1-S
      samples are very active in Beckmann rearrangement of cyclohexanone oxime, whereas
      TS-1-C samples are selective in adsorption for para-xylene.

PMID- 21079834
TI  - Spin relaxation of a short-lived radical in zero magnetic field.
AB  - A short-lived radical containing only one I = 1/2 nucleus, the muoniated 1,2
      dicarboxyvinyl radical dianion, was produced in an aqueous solution by the
      reaction of muonium with the dicarboxyacetylene dianion. The identity of the
      radical was confirmed by measuring the muon hyperfine coupling constant (hfcc) by
      transverse field muon spin rotation spectroscopy and comparing this value with
      the hfcc obtained from DFT calculations. The muon spin relaxation rate of this
      radical was measured as a function of temperature in zero magnetic field by the
      zero field muon spin relaxation technique. The results have been interpreted
      using the theoretical model of Fedin et al. (J. Chem. Phys., 2003, 118, 192). The
      muon spin polarization decreases exponentially with time after muon implantation
      and the temperature dependence of the spin relaxation rate indicates that the
      dominant relaxation mechanism is the modulation of the anisotropic hyperfine
      interaction due to molecular rotation. The effective radius of the radical in
      solution was determined to be 1.12 +/- 0.04 nm from the dependence of the muon
      spin relaxation rate on the temperature and viscosity of the solution, and is
      approximately 3.6 times larger than the value obtained from DFT calculations.

PMID- 21079833
TI  - Facile fabrication of robust multilayer films: visible light-triggered chemical
      cross-linking by the catalysis of a ruthenium(II) complex.
AB  - Highly stable covalently attached multilayer films were constructed by visible
      light irradiation of hydrogen-bonding directed multilayer films of
      poly(allylamine) and poly(4-vinylphenol).

PMID- 21079835
TI  - Malonate complexes of dysprosium: synthesis, characterization and application for
      LI-MOCVD of dysprosium containing thin films.
AB  - A series of malonate complexes of dysprosium were synthesized as potential
      metalorganic precursors for Dy containing oxide thin films using chemical vapor
      deposition (CVD) related techniques. The steric bulkiness of the dialkylmalonato
      ligand employed was systematically varied and its influence on the resulting
      structural and physico-chemical properties that is relevant for MOCVD was
      studied. Single crystal X-ray diffraction analysis revealed that the five
      homoleptic tris-malonato Dy complexes (1-5) are dimers with distorted square-face
      bicapped trigonal-prismatic geometry and a coordination number of eight. In an
      attempt to decrease the nuclearity and increase the solubility of the complexes
      in various solvents, the focus was to react these dimeric complexes with Lewis
      bases such as 2,2'-biypridyl and pyridine (6-9). This resulted in monomeric tris
      malonato mono Lewis base adduct complexes with improved thermal properties.
      Finally considering the ease of synthesis, the monomeric nature and promising
      thermal characteristics, the silymalonate adduct complex [Dy(dsml)(3)bipy] (8)
      was selected as single source precursor for growing DySi(x)O(y) thin films by
      liquid injection metalorganic chemical vapor deposition (LI-MOCVD) process. The
      as-deposited films were analyzed for their morphology and composition by scanning
      electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, Rutherford
      backscattering (RBS) analysis and X-ray photoelectron spectroscopy.

PMID- 21079836
TI  - Life cycle assessment of solar photo-Fenton and solar photoelectro-Fenton
      processes used for the degradation of aqueous alpha-methylphenylglycine.
AB  - A comparative Life Cycle Assessment (LCA) of solar photo-Fenton and solar
      photoelectro-Fenton, two solar-driven advanced oxidation processes (AOPs) devoted
      to the removal of non-biodegradable pollutants in water, is performed. The study
      is based on the removal, at laboratory scale, of the amino acid alpha
      methylphenylglycine, a good example of soluble and non-biodegradable target
      pollutant. The system under study includes chemicals, electricity, transport of
      all raw materials to the plant site, and the generation of emissions, but it does
      not take into account the impact of the infrastructure needed to build a
      hypothetical solar plant. Nine environmental impact categories are included in
      the LCA: global warming potential, ozone depletion potential, aquatic
      eutrophication potential, acidification potential, human toxicity potential,
      photochemical ozone formation potential, fresh water aquatic ecotoxicity
      potential, marine aquatic ecotoxicity potential, and terrestrial ecotoxicity
      potential and abiotic resource depletion potential. Although previous
      experimental results show that both AOPs are able to efficiently degrade the
      pollutant, the LCA indicates that solar-driven photo-Fenton is the most
      environmentally friendly alternative, mainly because the use of electricity in
      solar photoelectro-Fenton experiments involves high environmental impacts.

PMID- 21079837
TI  - Screening of a minimal enriched P450 BM3 mutant library for hydroxylation of
      cyclic and acyclic alkanes.
AB  - A minimal enriched P450 BM3 library was screened for the ability to oxidize inert
      cyclic and acyclic alkanes. The F87A/A328V mutant was found to effectively
      hydroxylate cyclooctane, cyclodecane and cyclododecane. F87V/A328F with high
      activity towards cyclooctane hydroxylated acyclic n-octane to 2-(R)-octanol (46%
      ee) with high regioselectivity (92%).

PMID- 21079838
TI  - Palladium catalyzed carboxylation of allylstannanes and boranes using CO2.
AB  - A family of well-defined (eta(3)-allyl)Pd(L)(carboxylate) (L = PR(3) or NHC)
      complexes are by far the most efficient catalysts reported to date for the
      catalytic carboxylation of allylstannanes into allylcarboxylates using CO(2). The
      substrate scope of this reaction is extended to both substituted allylstannanes
      and allylboranes.

PMID- 21079839
TI  - Extended para-hydrogenation monitored by NMR spectroscopy.
AB  - A system that provides a sustained hyperpolarized (1)H NMR signal in an aqueous
      medium is reported. The enhanced signal lasts much longer than typical (1)H T(1)
      values, uncovering new possibilities for implementing hyperpolarized (1)H NMR/MRI
      experiments or performing kinetics studies that would not otherwise be
      detectable.

PMID- 21079840
TI  - Application of the copper catalysed N-arylation of amidines in the synthesis of
      analogues of the chemical tool, blebbistatin.
AB  - A robust protocol for the CuI-catalysed arylation of amidines is presented.
      Whilst the initially identified conditions were useful for benzamidine-derived
      substrates, difficulties were encountered with more complex substrates. This
      problem was overcome following a change in ligand type, enabling the synthesis of
      analogues of the chemical tool, blebbistatin.

PMID- 21079841
TI  - A simple amine protection strategy for olefin metathesis reactions.
AB  - Acyclic diamines are valuable feedstocks for polyamide synthesis. Ruthenium
      alkylidene catalysed cross metathesis of amino alkenes is problematic and acyl
      derivatisation can result in less efficient syntheses, poor catalyst turnover and
      isomerisation. Temporary amine masking via stable and soluble ammonium salts
      delivers cyclic and acyclic aminoalkenes in high yield and purity.

PMID- 21079842
TI  - Anti-degradation of a recombinant complex protein by incorporation in small
      molecular hydrogels.
AB  - A phenomenon of anti-degradation of a recombinant complex protein (MPP6 complex
      protein) in a small molecular hydrogel was reported in this study.

PMID- 21079844
TI  - Molecular dynamics simulation of surface segregation in a (110) B2-NiAl thin
      film.
AB  - Surface segregation in (110) B2-NiAl film approximately 3 nm thick is
      investigated by using molecular dynamics simulation with a reliable embedded-atom
      potential. The simulation is performed for the stoichiometric composition at a
      temperature of 1500 K, just below the melting temperature of the film model. It
      is found that the (110) surface is structurally stable but develops adatoms,
      vacancies and antisites. The coverage of an adatom layer is estimated to be ~0.07
      ML (monatomic layers) and it contains on average ~95% of Al atoms. The top
      (surface) and second (subsurface) layers of the (110) surface is the most
      enriched in Ni relative to the bulk composition. These layers contain on average
      ~51% of Ni atoms. The Ni fraction in the third and forth layers of the film is
      estimated as ~50.5%. The deeper layers have essentially the bulk composition.
      Vacancies in the film model are found only on the Ni sublattice. The vacancy
      concentration on the Ni sublattice in the top layer is ~7.5%. The second layer
      almost does not contain vacancies. The next layers have essentially the constant
      bulk vacancy composition which can be estimated as ~1.3-1.4%.

PMID- 21079843
TI  - Nucleic acid detection using carbon nanoparticles as a fluorescent sensing
      platform.
AB  - In this communication, we demonstrate for the first time the proof of concept
      that carbon nanoparticles (CNPs) can be used as an effective fluorescent sensing
      platform for nucleic acid detection with selectivity down to single-base
      mismatch. The dye-labeled single-stranded DNA (ssDNA) probe is adsorbed onto the
      surface of the CNP via pi-pi interaction, quenching the dye. In the target assay,
      a double-stranded DNA (dsDNA) hybrid forms, recovering dye fluorescence.

PMID- 21079845
TI  - Carboxylic groups in mesoporous silica and ethane-bridged organosilica: effect of
      the surface on the reactivity.
AB  - Proton-donor ability of carboxylic groups incorporated by co-condensation into
      SBA-15 and ethane-bridged periodic mesoporous organosilica (PMO) has been studied
      through IR spectroscopy by dosing ammonia, which forms reversibly COO(-) groups
      and NH(4)(+) ions. The related equilibrium constants, determined by elaboration
      of IR data, reveal a lower reactivity of -COOH groups at the surface of PMO than
      on SBA-15, when the two samples have been outgassed at the same temperature. This
      finding is interpreted in terms of different dielectric constants and
      intermolecular interactions engaged with the surface species. Carboxylic groups
      on ethane-bridged organosilica react with silanols upon thermal treatment at 473
      K to form a mixed anhydride species Si-O-C(O)-, at variance with the same groups
      on SBA-15.

PMID- 21079850
TI  - Chemically immobilized T4-bacteriophage for specific Escherichia coli detection
      using surface plasmon resonance.
AB  - A bioassay platform using T4 bacteriophage (T4) as the specific receptor and
      surface plasmon resonance (SPR) as the transduction technique has been developed
      for the detection of Escherichia coli K12 bacteria. The T4 phages have been
      covalently immobilized onto gold surfaces using a self-assembled monolayer of
      dithiobis(succinimidyl propionate) (DTSP). Substrates of BSA/EA-T4/DTSP/Au
      prepared using different T4 phage concentrations have been characterized using
      scanning electron microscopy (SEM). The studies reveal that the use of DTSP
      results in a uniform binding of T4 phages onto the surface. The SPR analysis
      demonstrates that these BSA/EA-T4/DTSP/Au interfaces can detect the E. coli K12
      with high specificity against non-host E. coli NP10 and NP30. Results of SEM and
      SPR studies indicate that the maximum host bacterial capture is obtained when 1.5
      * 10(11) pfu ml(-1) concentration of T4 phages was used for immobilization. The
      surface of these chemically anchored phage substrates can be regenerated for
      repeated detection of E. coli K12 and can be used for detection in 7 * 10(2) to 7
      * 10(8) cfu ml(-1) range. The results of these studies have implications for the
      development of online bioassays for the detection of various food and water borne
      pathogens using the inherent selectivity of bacteriophage recognition.

PMID- 21079851
TI  - Nearly monodispersed core-shell structural Fe3O4@DFUR-LDH submicro particles for
      magnetically controlled drug delivery and release.
AB  - Nearly monodispersed magnetic Fe(3)O(4)@DFUR-LDH submicro particles containing
      the anticancer agent DFUR were prepared via a coprecipitation-calcination
      reconstruction strategy of LDH materials over the surface of Fe(3)O(4) particles,
      and present well-defined core-shell structure, strong magnetization and obvious
      magnetically controlled drug delivery and release properties.

PMID- 21079852
TI  - An efficient approach for production of polystyrene/poly(4-vinylpridine)
      particles with various morphologies based on dynamic control.
AB  - Polystyrene/poly(4-vinylpyridine) (PS/P4VP) particles with various morphologies
      such as popcorn-like (A), colloidal molecule NH(3) (B), colloidal molecule H(2)O
      (C) and mushroom-like (D) were generated by dynamically controlling and
      stabilizing the phase separation during the seeded swelling polymerization.

PMID- 21079854
TI  - Formation of identical-size graphene nanoclusters on Ru(0001).
AB  - Identical-size graphene nanoclusters (GNCs) form on Ru(0001) mediated by the
      substrate-induced clustering effect. The two kinds of uniform GNCs were
      identified as the seven C6-ring (noted as 7-C6) and three C6-ring (3-C6)
      structures with a dome-shape by using scanning tunneling microscopy.

PMID- 21079853
TI  - Introduction of beta-cyclodextrin into poly(aspartic acid) matrix for adsorption
      and time-release of ibuprofen.
AB  - Biodegradable copolymers with molecule inclusion ability was prepared by
      introduction of beta-cyclodextrin into poly(aspartic acid) matrices. The
      ibuprofen loading and dissolution properties of poly(aspartic acid)-beta
      cyclodextrin were investigated.

PMID- 21079855
TI  - Tubular microporous organic networks bearing imidazolium salts and their
      catalytic CO2 conversion to cyclic carbonates.
AB  - Tubular microporous organic networks bearing imidazolium salts (T-IM) were
      prepared by Sonogashira coupling of tetrakis(4-ethynylphenyl)methane and
      diiodoimidazolium salts, which showed promising catalytic activities in
      heterogeneous conversion of CO(2) into cyclic carbonates.

PMID- 21079856
TI  - New sulfur bridged neutral annulenes. Structure, physical properties and
      applications in organic field-effect transistors.
AB  - New, neutral, meso-substituted tetrathia[22]annulene[2,1,2,1] aromatic
      macrocyclic architectures display p-type semiconductor behaviour and constitute
      efficacious molecular field-effect transistors with reproducible bulk-like
      carrier mobility (as high as 0.63 cm(2) V(-1) S(-1)) on highly crystalline thin
      films deposited on octadecyltrichlorosilane modified SiO(2).

PMID- 21079857
TI  - SAXS investigation of a cubic to a sponge (L3) phase transition in self-assembled
      lipid nanocarriers.
AB  - The encapsulation and release of peptides, proteins, nucleic acids, and drugs in
      nanostructured lipid carriers depend on the type of the self-assembled liquid
      crystalline organization and the structural dimensions of the aqueous and
      membraneous compartments, which can be tuned by the multicomponent composition of
      the systems. In this work, small-angle X-ray scattering (SAXS) investigation is
      performed on the 'melting' transition of the bicontinuous double diamond cubic
      phase, formed by pure glycerol monooleate (MO), upon progressive inclusion of
      varying fractions of pharmaceutical-grade glycerol monooleate (GO) in the
      hydrated system. The self-assembled MO/GO mixtures are found to form diamond
      (Pn3m) inverted cubic, inverted hexagonal (H(II)), and sponge (L(3)) phases at
      ambient temperature in excess of aqueous medium without heat treatment. Mixing of
      the inverted-cubic-phase-forming MO and the sponge-phase-forming GO components,
      in equivalent proportions (50/50 w/w), yields an inverted hexagonal (H(II)) phase
      nanostructured carrier. Scattering models are applied for fitting of the
      experimental SAXS patterns and identification of the structural changes in the
      aqueous and lipid bilayer subcompartments. The possibility of transforming, at
      ambient temperature (20  degrees C), the bicontinuous cubic nanostructures into
      inverted hexagonal (H(II)) or sponge (L(3)) mesophases may facilitate novel
      biomedical applications of the investigated liquid crystalline self-assemblies.

PMID- 21079858
TI  - Mixed micellization between natural and synthetic block copolymers: beta-casein
      and Lutrol F-127.
AB  - Amphiphilic block copolymers and mixtures of amphiphiles find broad applications
      in numerous technologies, including pharma, food, cosmetic and detergency. Here
      we report on the interactions between a biological charged diblock copolymer,
      beta-casein, and a synthetic uncharged triblock copolymer, Lutrol F-127
      (EO(101)PO(56)EO(101)), on their mixed micellization characteristics and the
      micelles' structure and morphology. Isothermal titration calorimetry (ITC)
      experiments indicate that mixed micelles form when Lutrol is added to monomeric
      as well as to assembled beta-casein. The main driving force for the mixed
      micellization is the hydrophobic interactions. Above beta-casein CMC, strong
      perturbations caused by penetration of the hydrophobic oxypropylene sections of
      Lutrol into the protein micellar core lead to disintegration of the micelles and
      reformation of mixed Lutrol/beta-casein micelles. The negative enthalpy of
      micelle formation (DeltaH) and cooperativity increase with raising beta-casein
      concentration in solution. zeta-potential measurements show that Lutrol interacts
      with the protein micelles to form mixed micelles even below its critical
      micellization temperature (CMT). They further indicate that Lutrol effectively
      masks the protein charges, probably by forming a coating layer of the
      ethyleneoxide rich chains. Small-angle X-ray scattering (SAXS) and cryogenic
      transmission electron microscopy (cryo-TEM) indicate relatively small changes in
      the oblate micellar shape, but do show swelling along the small axis of beta
      casein micelles in the presence of Lutrol, thereby confirming the formation of
      mixed micelles.

PMID- 21079859
TI  - Chiral mesoporous silica: chiral construction and imprinting via cooperative self
      assembly of amphiphiles and silica precursors.
AB  - Fabrication of chiral materials and revealing the mechanisms involved in their
      formation are crucial issues in scientific research. The combination of
      cooperative self-assembly routes and the chiral templating process favors the
      formation of inorganic chiral materials with highly ordered mesostructures. This
      tutorial review highlights the recent research on chiral mesoporous silica (CMS)
      of hierarchical helical constructions transcribed from organic templates. The
      rules and mechanisms involved in the synthesis of CMS and related materials,
      especially the novel expression of chirality and imprinting of helical micellar
      superstructure by the functional groups immobilized on the mesopore surface,
      provide us with a deeper insight into the chiral self-assembly process and new
      strategies for the design and application of chiral materials. This review is
      addressed to researchers and students interested in chiral chemistry,
      supramolecular chemistry and mesoporous materials (53 references).

PMID- 21079860
TI  - Diastereotopos-differentiating C-H activation reactions at methylene groups.
AB  - The activation of C-H bonds has become a widely used method which allows for the
      direct transformation of C-H bonds into synthetically more valuable C-C and C-X
      bonds in a selective manner. This critical review aims to summarize and to
      highlight a specific subgroup of these transformations, C-H activation reactions
      of chiral substrates bearing diastereotopic hydrogen atoms at methylene groups
      (95 references).

PMID- 21079861
TI  - Understanding chemical reaction mechanisms in ionic liquids: successes and
      challenges.
AB  - The focus of this article is an examination of chemical reaction mechanisms in
      ionic liquids. These mechanisms are compared with those pertaining to the same
      reactions carried out in conventional solvents. In cases where the mechanisms
      differ, attempts to provide an explanation in terms of the chemical and
      physicochemical properties of the reactants and of the components of the ionic
      liquids are described. A wide range of reactions from different branches of
      chemistry has been selected for this purpose. A sufficient background for student
      readers has been included. This tutorial review should also be of interest to
      kineticists, and to both new and experienced investigators in the ionic liquids
      field.

PMID- 21079863
TI  - Recent advances in catalytic asymmetric epoxidation using the environmentally
      benign oxidant hydrogen peroxide and its derivatives.
AB  - There has been a recent drive to develop asymmetric catalytic methods to produce
      epoxides using environmentally benign oxidants, especially hydrogen peroxide.
      This critical review discusses the advances that have been made using both metal
      based and organocatalytic homogeneous catalysts (142 references).

PMID- 21079864
TI  - Cyclopentadienyl mesityl complexes of chromium(II) and chromium(III).
AB  - Chromium(III) mesityl complexes were synthesized by protonolysis of chromocene
      with 1,3-diisopropylimidazolium chloride or DBU hydrochloride, salt metathesis
      with MesMgBr, and single electron oxidation with iodine.

PMID- 21079862
TI  - Enzymatic functionalization of carbon-hydrogen bonds.
AB  - The development of new catalytic methods to functionalize carbon-hydrogen (C-H)
      bonds continues to progress at a rapid pace due to the significant economic and
      environmental benefits of these transformations over traditional synthetic
      methods. In nature, enzymes catalyze regio- and stereoselective C-H bond
      functionalization using transformations ranging from hydroxylation to
      hydroalkylation under ambient reaction conditions. The efficiency of these
      enzymes relative to analogous chemical processes has led to their increased use
      as biocatalysts in preparative and industrial applications. Furthermore, unlike
      small molecule catalysts, enzymes can be systematically optimized via directed
      evolution for a particular application and can be expressed in vivo to augment
      the biosynthetic capability of living organisms. While a variety of technical
      challenges must still be overcome for practical application of many enzymes for C
      H bond functionalization, continued research on natural enzymes and on novel
      artificial metalloenzymes will lead to improved synthetic processes for efficient
      synthesis of complex molecules. In this critical review, we discuss the most
      prevalent mechanistic strategies used by enzymes to functionalize non-acidic C-H
      bonds, the application and evolution of these enzymes for chemical synthesis, and
      a number of potential biosynthetic capabilities uniquely enabled by these
      powerful catalysts (110 references).

PMID- 21079865
TI  - Widespread microbiological groundwater contamination in the South-eastern Salento
      (Puglia-Italy).
AB  - In the Salento peninsula (Puglia Region, South-East Italy), underground waters
      are a fundamental resource for the population because they constitute the
      principal reservoir for drinking water and irrigation. They are, however,
      affected by overexploitation. The risk factors in the Salento arise mainly from
      anthropic activities, especially tourism and agriculture (leaking wells, sewage
      and inadequate waste disposal procedures). The Southern Salento is recognized to
      be at high risk of pathologies characterised by oral-faecal transmission. From
      2001 to 2009 the incidence of typhoid fever in the Salento was 12.11/100,000
      inhabitants as against 2.91 in Italy. Enteritis caused by rotaviruses is an
      important cause of hospitalization of paediatric-aged children in the Salento,
      with high social costs. An effective monitoring system for the conservation and
      management of water bodies and the protection of public health is therefore
      fundamental. The present study sought to determine the microbiological and
      chemical-physical quality of groundwater in the Salento and to analyse the
      factors associated with contamination. The results indicated widespread pollution
      from salt and microbial contamination. Contamination from faecal microorganisms
      posed a significant risk of human infection in 100% of samples. Furthermore, the
      water was unsuitable even for irrigation in a high percentage of cases (31.8%),
      which is of considerable significance given that agriculture is one of the most
      important economic activities in the area under study. The high salt
      concentration was probably due to excessive extraction of water for intensive
      irrigation, especially in summer. Under these circumstances, some of mitigation
      activity is necessary. Furthermore, it would be advisable to decrease the
      pollution load from anthropic activities in the territory and to reduce water
      consumption in order to conserve groundwater resources especially.

PMID- 21079866
TI  - Structural basis for the potential antitumour activity of DNA-interacting
      benzo[kl]xanthene lignans.
AB  - The biological properties and possible pharmacological applications of
      benzo[kl]xanthene lignans, rare among natural products and synthetic compounds,
      are almost unexplored. In the present contribution, the possible interaction of
      six synthetic benzo[kl]xanthene lignans and the natural metabolite rufescidride
      with DNA has been investigated through a combined STD-NMR and molecular docking
      approach, paralleled by in vitro biological assays on their antiproliferative
      activity towards two different cancer cell lines: SW 480 and HepG2. Our data
      suggest that the benzo[kl]xanthene lignans are suitable lead compounds for the
      design of DNA selective ligands with potential antitumour properties.

PMID- 21079867
TI  - New synthesis of meso-free-[14]triphyrin(2.1.1) by McMurry coupling and its
      derivatization to Mn(I) and Re(I) complexes.
AB  - The metal-free and meso-free [14]triphyrin(2.1.1) compound was successfully
      prepared based on the intramolecular McMurry coupling reaction of diformyl
      tripyrrane in 16% yield, and was converted to the bowl-shaped Mn(I)(TriP)(CO)(3)
      and Re(I)(TriP)(CO)(3).

PMID- 21079868
TI  - Biomimetic mineralization of vertical N-doped carbon nanotubes.
AB  - Biomimetic mineralization of vertical N-doped carbon nanotubes is demonstrated as
      a straightforward route for carbon-based mineral nanocomposites. The N-doped
      sites along the carbon nanotube backbone play the role of nucleation sites for
      mineralization.

PMID- 21079869
TI  - Structure and stability of one-dimensional o-phthalaldehyde lines on the Si(100)
      2 * 1:H surface.
AB  - We present the structural models for the o-phthalaldehyde (OP) molecular lines on
      the H-terminated Si(100) surface which were recently observed by scanning
      tunnelling microscopy. Our first-principles density-functional theory
      calculations show that the formation of OP lines is not only kinetically more
      facile but also thermodynamically more stable than those of previously reported
      alkene lines.

PMID- 21079870
TI  - Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of
      actin cytoskeleton in renal tubular epithelial cells.
AB  - In vivo, renal tubular epithelial cells are exposed to luminal fluid shear stress
      (FSS) and a transepithelial osmotic gradient. In this study, we used a simple
      collecting-duct-on-a-chip to investigate the role of an altered luminal
      microenvironment in the translocation of aquaporin-2 (AQP2) and the
      reorganization of actin cytoskeleton (F-actin) in primary cultured inner
      medullary collecting duct (IMCD) cells of rat kidney. Immunocytochemistry
      demonstrated that 3 h of exposure to luminal FSS at 1 dyn cm(-2) was sufficient
      to induce depolymerization of F-actin in those cells. We observed full actin
      depolymerization after 5 h exposure and substantial re-polymerization within 2 h
      of removing the luminal FSS, suggesting that the process is reversible and the
      fluidic environment regulates the reorganization of intracellular F-actin. We
      demonstrate that several factors (i.e., luminal FSS, hormonal stimulation,
      transepithelial osmotic gradient) collectively exert a profound effect on the
      AQP2 trafficking in the collecting ducts, which is associated with actin
      cytoskeletal reorganization.

PMID- 21079872
TI  - Dipyrrin based silver [2 + 2] metallamacrocycles.
AB  - The synthesis and characterization of a series of [2 + 2] metallamacrocycles
      based on combinations of silver salts AgX (X = BF(4)(-), PF(6)(-), SbF(6)(-),
      TfO(-)) with pyridyl, p-phenyl-pyridyl and p-phenyl-imidazolyl appended dipyrrin
      (dpm) derivatives is reported. In these species, the silver ion is linearly
      coordinated to one of the two pyrrolic groups of the dpm moiety through the
      nitrogen atom and to a N atom belonging to the peripheral coordinating group. The
      organisation of the cyclic complexes in the solid state is dependent on the
      nature of the anion X(-) and on the hydrogen bonding patterns formed with the
      pyrrolic NH group, acting as a donor. Furthermore, in some cases, d(10)-d(10)
      argentophilic interactions are observed between consecutive macrocyclic complexes
      in the crystalline phase. The robustness of some of the complexes obtained
      compounds was investigated by (1)H- and (13)C-NMR spectroscopy which revealed the
      structural integrity of the cyclic species in solution. A DOSY NMR study on the
      cyclic entity based on the imidazolyl appended dpm further assessed that the
      complex present in solution was indeed the [2 + 2] metallamacrocycle.

PMID- 21079871
TI  - Ribonuclease S redux.
AB  - The S-peptide and S-protein components of bovine pancreatic ribonuclease form a
      noncovalent complex with restored ribonucleolytic activity. Although this
      archetypal protein-fragment complementation system has been the object of
      historic work in protein chemistry, intrinsic limitations compromise its utility.
      Modern methods are shown to overcome those limitations and enable new
      applications.

PMID- 21079873
TI  - Microarrays for the scalable production of metabolically relevant tumour
      spheroids: a tool for modulating chemosensitivity traits.
AB  - We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for the
      arrayed mass production of highly uniform 3-D human HT29 colon carcinoma
      spheroids. The spheroids have an organotypic density and, as determined by 3-axis
      imaging, were genuinely spherical. Critically, the array density impacts growth
      kinetics and can be tuned to produce spheroids ranging in diameter from 200 to
      550 um. The diffusive limit of competition for media occurred with a pitch of
      >=1250 um and was used for the optimal array-based culture of large, viable
      spheroids. During sustained culture mass transfer gradients surrounding and
      within the spheroids are established, and lead to growth cessation, altered
      expression patterns and the formation of a central secondary necrosis. These
      features reflect the microenvironment of avascularised tumours, making the array
      format well suited for the production of model tumours with defined sizes and
      thus defined spatio-temporal pathophysiological gradients. Experimental windows,
      before and after the onset of hypoxia, were identified and used with an enzyme
      activity-based viability assay to measure the chemosensitivity towards
      irinotecan. Compared to monolayer cultures, a marked reduction in the drug
      efficacy towards the different spheroid culture states was observed and
      attributed to cell cycle arrest, the 3-D character, scale and/or hypoxia factors.
      In summary, spheroid culture using the array format has great potential to
      support drug discovery and development, as well as tumour biology research.

PMID- 21079874
TI  - A fast and simple method to fabricate circular microchannels in
      polydimethylsiloxane (PDMS).
AB  - A simple method to fabricate circular microchannels in polydimethylsiloxane
      (PDMS) is presented. A coating of liquid PDMS is applied on the walls of
      rectangular microchannels, fabricated using standard soft-lithography, by
      introducing a pressurized air stream inside the PDMS filled microchannels.
      Surface tension of the liquid PDMS forces the coating to take a circular cross
      section which is preserved by baking the device to cure the coated layer.
      Diameters ranging from a few micrometres to a few hundreds of micrometres were
      achieved. The method was verified to work on microchannel networks as well as in
      straight channels. Different coating conditions were systematically tested.
      Design curves are reported for one to choose appropriate coating conditions for
      obtaining a desired diameter. A comparison between the performance of square and
      circular microchannels in trapping SiHa cells (cervical cancer cell line) is
      shown.

PMID- 21079875
TI  - Surface modification for small-molecule microarrays and its application to the
      discovery of a tyrosinase inhibitor.
AB  - Small-molecule microarrays are powerful, high-throughput tools for gathering
      information about direct binding events between proteins of interest and small
      molecules. However, nonspecific binding on modified glass slides is the major
      factor reducing the quality of information obtained in proteomic screening with
      small-molecule microarrays. To improve the signal-to-noise ratio by suppressing
      the background signal, we tested several surface modification methods for glass
      slides. Jeffamine-coated slides showed a high fluorescence signal and a
      significantly enhanced signal-to-noise ratio. We applied this surface
      modification to proteomic screening of potential tyrosinase inhibitors with a
      small-molecule microarray and identified 2,4,4'-trihydroxychalcone as a new small
      molecule binder to tyrosinase. Its actual binding and inhibitory effects on
      tyrosinase were validated using an SPR binding assay and an enzyme-based
      inhibition assay, respectively. Thus, we successfully demonstrate the application
      of Jeffamine-based modification to proteomics screening with small-molecule
      microarrays.

PMID- 21079876
TI  - A concise synthesis of the molecular framework of pleuromutilin.
AB  - Two syntheses of the tricyclic carbon skeleton of pleuromutilin are reported.
      Diastereoselective 1,4-conjugate additions were used to elaborate bicyclic
      precursors at an early stage of each route, while ring-forming olefin metatheses
      were executed to complete the pleuromutilin carbon framework. The congeners
      prepared are appropriately functionalized to enable access to diverse
      pleuromutilin analogues.

PMID- 21079877
TI  - Made-to-order nanocarbons through deterministic plasma nanotechnology.
AB  - Through a combinatorial approach involving experimental measurement and plasma
      modelling, it is shown that a high degree of control over diamond-like nanocarbon
      film sp3/sp2 ratio (and hence film properties) may be exercised, starting at the
      level of electrons (through modification of the plasma electron energy
      distribution function). Hydrogenated amorphous carbon nanoparticle films with
      high percentages of diamond-like bonds are grown using a middle-frequency (2 MHz)
      inductively coupled Ar+CH4 plasma. The sp3 fractions measured by X-ray
      photoelectron spectroscopy (XPS) and Raman spectroscopy in the thin films are
      explained qualitatively using sp3/sp2 ratios 1) derived from calculated sp3 and
      sp2 hybridized precursor species densities in a global plasma discharge model and
      2) measured experimentally. It is shown that at high discharge power and lower
      CH4 concentrations, the sp3/sp2 fraction is higher. Our results suggest that a
      combination of predictive modeling and experimental studies is instrumental to
      achieve deterministically grown made-to-order diamond-like nanocarbons suitable
      for a variety of applications spanning from nano-magnetic resonance imaging to
      spin-flip quantum information devices. This deterministic approach can be
      extended to graphene, carbon nanotips, nanodiamond and other nanocarbon materials
      for a variety of applications.

PMID- 21079878
TI  - Oxidoreductive coupling of thiols with aryl halides catalyzed by copper on iron.
AB  - Synthesis and utilization of a simple copper on iron catalyst in the coupling of
      aryl halides with thiols through disulfide intermediate is reported. The iron
      support of copper catalyst ensures reductive media for the coupling, allows easy
      removal of the metals by outer magnetic field and enables the recycling of the
      catalyst.

PMID- 21079879
TI  - An EMF cell with a nitrogen solid electrolyte--on the transference of nitrogen
      ions in yttria-stabilized zirconia.
AB  - The mobility and electrochemical activity of nitrogen inside and/or at the
      surface of ionic compounds is of fundamental, as well as of possibly practical,
      relevance. In order to better understand the role of nitrogen anions in solid
      electrolytes, we measured the transference number of nitrogen in yttria
      stabilized zirconia (YSZ) by a concentration cell technique as a function of
      oxygen activity at different temperatures in the range of 1023 <=T/K<= 1123. YSZ
      doped with 1.9 wt% of N (YSZ:N) turned out to have an appreciable nitrogen
      transference number, which increased from 0 to 0.1 with decreasing oxygen
      activity in the range of -20 < log a(O(2)) < -14. The stability of N in YSZ:N,
      however, has yet to be elucidated under oxidizing conditions.

PMID- 21079880
TI  - Liquid chromatographic high-throughput analysis of the new ultra-short acting
      hypnotic 'HIE-124' and its metabolite in mice serum using a monolithic silica
      column.
AB  - For the first time, a fast, high-performance liquid chromatography (HPLC) method
      was developed and validated for the simultaneous determination of the new ultra
      short hypnotic HIE-124 and its metabolite in mice serum. Each compound, together
      with carbamazepine (internal standard) was extracted from the serum matrix using
      liquid-liquid extraction (LLE). Chromatographic resolution of the analytes was
      performed on a Chromolith Speed Rod monolithic silica column (100 mm * 4.6 mm
      i.d.) under isocratic conditions using a mobile phase of 65:35 (v/v), 20 mM
      phosphate buffer (pH 7.0 adjusted with phosphoric acid)-acetonitrile. The elution
      of the analytes were monitored at 240 nm and conducted at ambient temperature.
      Because of high column efficiency the mobile phase was pumped at a flow rate of
      2.5 mL min(-1). The total run time of the assay was 2 min. The method was
      validated over the range of 60-2000 ng mL(-1) for HIE-124 and 200-1600 ng mL(-1)
      for the metabolite (r(2) = 0.99). The limit of detection (LOD) for HIE-124 and
      its metabolite were 20 ng mL(-1) and 65 ng mL(-1), respectively. The proposed
      method was validated in compliance with ICH guidelines, in terms of accuracy,
      precision, limits of detection and quantitation and other aspects of analytical
      validation. The developed method could be used for the trace analyses of HIE-124
      and its metabolite in serum and was finally used for the pharmacokinetic study
      investigation of HIE-124 in mice serum.

PMID- 21079881
TI  - Electric detection of DNA with PDMS microgap electrodes and silver nanoparticles.
AB  - In this work a novel microdevice sensor has been developed by plating gold on the
      PDMS surface to generate a sandwich-type gap electrode for DNA detection. The
      microdevice utilizes a gold band electrode-PDMS-gold band electrode configuration
      and the minimum detectable volume could be as low as 5 MUL. The 20 MUm PDMS-based
      gap was chemically modified with DNA capture probes and DNA sandwich hybrids were
      formed with the addition of DNA target and silver nanoparticle probes. To
      increase detection sensitivity, parallel detection zones have been developed in
      which the relevant resistances decrease substantially upon hybridyzation. By
      measuring the change in electrical conductivity, the DNA target in the
      concentration range of 1000-0.1 nM can be assayed and the limit of lowest
      detectable concentration was achieved at 0.01 nM.

PMID- 21079882
TI  - G-Quadruplex-based DNAzyme for colorimetric detection of cocaine: using magnetic
      nanoparticles as the separation and amplification element.
AB  - The appearance of the aptamer provides good recognition elements for small
      molecules, especially for drugs. In this work, by combining the advantages of
      magnetic nanoparticles (MNPs) with colorimetric drug detection using hemin-G
      quadruplex complex as the sensing element, we report a simple and sensitive
      DNAzyme-based colorimetric sensor for cocaine detection in a 3,3,5,5
      tetramethylbenzidine sulfate (TMB)-H(2)O(2) reaction system. The whole
      experimental processes are simplified. Cocaine aptamer fragments, SH-C2, are
      covalently labeled onto the amine-functionalized MNPs. When the target cocaine
      and another cocaine aptamer fragments (C1) grafted with G-riched strand AG4 (i.e.
      C1-AG4) are present simultaneously, the C2 layer on MNPs hybridizes partly with
      C1-AG4 to bind the cocaine. The C1-AG4 can be combinded with hemin to form
      DNAzyme which can effectively catalyze the H(2)O(2)-mediated oxidation of TMB,
      giving rise to a change in solution color. Importantly, using MNPs as the
      separation and amplification elements could effectively reduce the background
      signal and the interference from the real samples. A linear response from 0.1 MUM
      to 20 MUM is obtained for cocaine and a detection limit of 50 nM is achieved,
      which provides high sensitivity and selectivity to detect cocaine.

PMID- 21079883
TI  - A catechol-terminated self-assembled monolayer at the surface of a gold electrode
      and its application for the electrocatalytic determination of dopamine.
AB  - An electroactive self-assembled monolayer was fabricated by covalent attachment
      of protocatechuic acid at a gold surface and its electrochemical behavior was
      investigated using cyclic voltammetry. The modification involves a three-step
      method: (i) preparation of a cysteamine self-assembled monolayer, (ii) activation
      of the carboxylic groups of protocatechuic acid in solution and (iii)
      modification of cysteamine self-assembled monolayers by activated protocatechuic
      acid to functionalize the self-assembled monolayer by catechol-terminated groups.
      This resulting thin film modified electrode was tested successfully for the
      electrocatalytic determination of dopamine in aqueous solution.

PMID- 21079884
TI  - Highly spectral dependent enhancement of upconversion emission with sputtered
      gold island films.
AB  - We report a five-fold overall enhancement of upconversion emission in NaYF(4) :
      Yb/Er nanocrystals when coupled with gold island films. Spectroscopic studies
      show that the enhancement factors are highly dependent on the exact spectral
      positions and excitation power density, with a largest enhancement factor of more
      than 12 observed at selected spectral positions, which may be attributed to
      different upconversion processes involved.

PMID- 21079886
TI  - [The bioethics in surgery].

PMID- 21079887
TI  - [Touchstone change in QUALIS!].

PMID- 21079885
TI  - Dynamic expression of Qa-2 during acute graft rejection.
AB  - Human leukocyte antigen (HLA)-G exhibits immunotolerogenicity and is related to
      allograft acceptance. Qa-2 is the murine homolog of HLA-G; it has structure and
      functions similar to those of HLA-G. We investigated the dynamic expression of Qa
      2 in skin allografts by immunohistochemistry and on peripheral blood lymphocyte
      subsets by flow cytometry during the entire process of acute graft rejection
      (AGR) with a murine skin transplantation model to determine its relationship with
      the pathological changes of allografts and the influence of immunosuppressive
      therapy. In grafts without immunosuppressive treatment, Qa-2 did not exhibit
      obvious changes in syngeneic and allogeneic recipients. In contrast, with
      immunosuppressant-treated grafts, positive expression of Qa-2 was observed. It
      remained at high levels in the immunosuppressant-treated syngeneic group;
      however, it became weakly positive and even negative in infiltrating inflammatory
      cells as AGR advanced, but it remained strongly positive in other skin tissues
      throughout the AGR process. Qa-2 expression on CD4(+) and CD8(+) peripheral blood
      lymphocyte subsets remained stable at a normal level in the non-immunosuppressant
      treated syngeneic group. Immunosuppressive treatment can also significantly
      upregulate Qa-2. In the allogeneic groups, decreased expression was observed when
      AGR was at histological grades 1 to 2 (well before gross rejection was observed).
      Qa-2 was upregulated again after the graft was rejected completely. The results
      suggest that the increase in Qa-2 may be attributed to the use of
      immunosuppressive treatments. Moreover, Qa-2 expression decreased significantly
      with AGR progression, suggesting that it may be a potential marker for predicting
      AGR, especially in the presence of immunosuppressive agents.

PMID- 21079888
TI  - [Transhiatal versus transthoracic esophagectomy: experience of the Brazilian
      National Cancer Institute].
AB  - OBJECTIVE: Analyses of morbidity, mortality and overall survival after
      transhiatal (TH) or transthoracic (TT) esophagectomy. METHODS: Retrospective non
      randomized study of 68 patients with esophagus neoplasia operated in the
      Brazilian National Cancer Institute between 1997 and 2005. We divided in two
      groups: Group 1--TH (33 patients); and Group 2--TT (35 patients). RESULTS: The
      mean age was 40.7 years old (25-74 years old), being 73.5% male. Middle third
      tumors predominated in Group 2 (48.6% vs. 21.2%, p = 0,02). The mean of dissected
      lymph nodes was biggest in Group 2 (21.6 vs. 17.8 lymph nodes, p = 0.04), however
      without difference in number of metastatic lymph nodes (4.1 vs. 3.9 linfonodos, p
      = 0.85). The mean of operative time was higher in Group 2 (410 vs. 270 minutes, p
      = 0.001). Also the mean of length of stay was higher in Group 2 (19 vs. 14 days,
      p = 0.001). The operative morbidity was 50%, without statistical difference
      between the groups (42.4% vs. 57.1%, p = 0,23). Esophageal leakage occurred in
      13.2% of cases, also without statistical difference (9.1% vs. 17.1%, p = 0.23).
      The mortality was 5.8% (04 patients), without statistical difference (1.4% vs.
      4.4%, p = 0,83). CONCLUSION: In our study, the morbidity and mortality showed no
      statistical difference in relation to the access performed, although higher
      operative time and length of stay were observed in TT access. The 3 and 5-years
      overall survival also were biggest in TT access, probably due to the biggest
      frequency of patients on initial stages between the submitted to the TT access.

PMID- 21079889
TI  - [Skin-adipose tissue detachment for laparotomy closure: a simple and effective
      technique for a complex problem].
AB  - OBJECTIVE: To describe a technique of laparotomy closure through cutaneous
      adipose tissues detachment and its results. METHODS: From January 2003 to october
      2008 forty patients in laparotomy (Bogota bag) were engaged in surgical
      procedures for closing their open abdomens according to the technique described
      here. Data were collected from patient records and during active search. RESULTS:
      The majority of patients was men (95%) with gunshot wounds (70%). The average ISS
      and APACHE II scores were 28.78 and 20, respectively. Ventral hernias were found
      in 81.5% of patients with a mean follow-up time of 9.2 months. Approximately 1/3
      of patients had small hernias and didn't want to have their hernias closed
      because they didn't feel any functional or anatomic impediment to support the
      closure at that time. Only two patients were dissatisfied in relation to daily
      activities and to the surgical procedure itself. There were neither deaths nor
      intestinal fistula with this type of closure. CONCLUSION: Although it doesn't
      represent a technique for fascial closure, it is simple to perform, safe, and
      with low cost. It is a therapeutic option for patients with open abdomen,
      especially if closure of the aponeurosis was not possible in the first 7 to 10
      days.

PMID- 21079890
TI  - [Learning curve and iatrogenic injuries in laparoscopic cholecystectomies].
AB  - OBJECTIVE: The aim of this study is to analyze surgeon's proficiency, based on
      the different aspects of his learning curve as a risk factor for iatrogenic
      biliary tract injuries associated with Laparoscopic Cholecystectomy. METHODS: a
      retrospective study was conducted using the report information from charts of
      patients January 1992 through December 2007; at Hospital Universitario Clementino
      Fraga Filho da Universidade Federal do Rio de Janeiro. Analysis from data
      collected from charts of 2285 patients who had undergone laparoscopic
      cholecystectomies. Data from surgeons involved with this type of surgery was also
      analyzed. RESULTS: a total of six injuries (0.26%) were found. This result is
      similar to that found in international publications. All injuries had occurred in
      the surgeon's second phase of the learning curve with more than 50 video
      surgeries. CONCLUSION: it was conclude that Video surgery Certificate and
      previous training are not related to biliary tract injuries in this series.
      Surgeon's age was not a risk factor in this study. There was statistical
      significance between surgeons' experience and injuries.

PMID- 21079891
TI  - [Prospective comparative study of ERCP brush cytology and EUS-FNA for the
      differential diagnosis of biliary strictures].
AB  - OBJECTIVE: To evaluate and to compare the diagnostic yield of ERCP brush cytology
      (ERCP) and EUS-FNA in patients with biliary strictures and evaluates the
      agreement between general pathologists (GP) and expert GI pathologists (GIP) in
      the final diagnosis of biliary strictures. METHODS: Patients with biliary
      strictures documented by ERCP were included. Brush cytology was performed and
      during EUS, only visible mass lesions or localized bile duct wall thickening were
      aspirated. The gold standard method for diagnosis was surgical histology and/or
      follow-up. Tissue sampling results were: malignant, suspicious, atypical,
      insufficiently or benign. Specimens were interpreted by GP and GIP, blinded for
      prior tests results. RESULTS: 46 patients were included. Final diagnosis was
      malignancy in 37 (26 pancreatic--11 biliary) and benign in 9 (8 chronic
      pancreatitis--1 common bile duct inflammatory stricture). Sensitivity and
      accuracy for ERCP brush cytology were 43.2% and 52.2% for GP and 51.4% and 58.7%
      for GIP. Sensitivity and accuracy for EUS-FNA were 52.8% and 58.5%, respectively
      for GP and 69.4% e 73.2% for GIP. In comparison, the combination of brush
      cytology and EUS-FNA demonstrated higher sensitivity and accuracy for both GP
      (64.9% and 69.6%, respectively) and GIP (83.8% and 84.8%, respectively) and
      improved agreement with final diagnosis for both (mostly for GIP). CONCLUSION:
      Both, ERCP brush cytology and EUS-FNA has a similar yield for the diagnosis of
      biliary strictures. However, the combination of these methods results in an
      improved diagnostic accuracy. In addition, GIP might be expected to interpret
      specimens with greater accuracy than GP.

PMID- 21079892
TI  - [Degloving injuries of lower extremity--proposal of a treatment protocol].
AB  - OBJECTIVE: Degloving injuries on the lower extremities are often serious
      injuries. It is difficult to decide on the most appropriate treatment, whether
      flap repositioning and suturing or converting the avulsed flap to split-thickness
      skin grafting. METHODS: This study assessed patients with degloving injuries in
      lower extremities, reviewing the epidemiological profile and treatment performed.
      It is proposed a treatment protocol for management of those lower extremity
      avulsion injuries. RESULTS: Twenty-one patients were evaluated. The cause of
      trauma was running over in 11 patients (52.4%) and motorcycle accident in 10
      (47.6%). All twenty-one patients had treatment with washing, debridement,
      resection of avulsed flap and converting the flap to split-thickness graft, in
      according with the following treatment protocol for management of those lower
      extremity avulsion injuries that came to our Emergency Unit: Patients were
      initially classified as unstable or stable (hemodynamically). In the unstable
      group (two patients),due to the patient condition, flap resection was performed
      and the skin kept in the tissue bank for later grafting. In the stable group (19
      patients), flap viability was assessed using clinical parameters and fluorescein.
      If deemed viable the flap was sutured to its original position. If deemed
      unviable (all 19 patients), it was resected and converted to split-thickness skin
      and mesh grafting with vacuum-assisted device over the graft. CONCLUSION: In
      order to avoid flap necrosis and to add a new skin donor area is important to
      recognize the problem in the Emergency Room and to manage properly those
      injuries.

PMID- 21079893
TI  - [Evaluation of venous thromboembolism prophylaxis in a high complexity hospital].
AB  - OBJECTIVE: This study aimed at assessing the adequacy of thromboprophylaxis in a
      high complexity hospital in Vitoria-ES, analysing the possible predictors of
      inadequate prescriptions and/or procedures. METHODS: A cross-sectional study was
      carried out through prompt-book analysis. The included patients were hospitalized
      in 2007 and had their Venous thromboembolism (VTE) risk stratified using the 8th
      Edition of the American College of Chest Physicians (ACCP) Evidence-Based
      Clinical Practice Guidelines. The thromboprophylaxis adequacy was determined
      through a comparison between the adopted prescriptions and/or procedures and the
      guideline recommendations. EpiInfo 3.4.3 and SPSS 13.0 were the software
      applications used. RESULTS: In 47% of the patients the thromboprophylaxis was
      inadequate, being the non-prescription of the indicated medication the major
      reason (33%). There was no statistically significant difference in inadequate
      tromboprophylaxis rate between clinical and surgical patients, or ward and
      Intensive care unit (ICU) ones. An inverse relationship was observed between the
      inadequate tromboprophylaxis rate and the number of VTE risk factors presented by
      the patients, as well as their age, and the length of hospital stay (p < 0.05).
      CONCLUSION: The results show alarming levels of thromboprophylaxis inadequacy,
      inacceptable in these times of well-established published guidelines. Therefore,
      a continuing education program should be implanted for all the assistance team.

PMID- 21079894
TI  - [Prevention of normothermic hepatic ischemia during in situ liver perfusion with
      three different preservation solutions: experimental analysis by realtime
      infrared radiation thermography].
AB  - OBJECTIVE: To establish the usefulness of infrared radiation thermography on
      monitoring in situ liver perfusion with different preservation solutions during
      liver harvesting. METHODS: Twenty-four adult male Wistar rats, weighing 385.31 g
      were randomly divided into four groups of six animals each according to the
      solution used to perfuse the liver (Euro-Collins(r) solution--EC group;
      Custodiol(r) solution--CUST group; Celsior(r) solution--CEL group and Ringer
      Lactate solution--RL group). Under inhalatory ether anesthesia, animals were
      submitted to upper transversal laparotomy, exposure of median and left-lateral
      hepatic lobes, heparin injection (500 UI/Kg) through infrahepatic vena cava,
      portal vein infusion through 18G catheter of cold (4 degrees C) solution
      according to the group of study. Infrared images, with respective temperature
      evaluations from hepatic surface, were picked up in real time by Therma CAM
      SC500(r) infrared camera positioned at constant distance from three fixed points
      of the diaphragmatic surface of median and left lateral lobes at the following
      moments regarding liver perfusion: immediately after laparotomy; after portal
      vein cannulation and immediately before solution infusion; at each minute from
      the beginning of liver perfusion during five minutes. Mean temperatures of each
      moment were compared intra and intergroups with the difference between means test
      with normal distribution, with significance level of 5% (p=0.05). RESULTS: There
      was statistically significant difference of means temperatures between the moment
      of laparotomy and immediately after cannulation; between this later and after the
      first minute of perfusion; and between the first and fifth minutes of infusion in
      all groups of study in a similar way. CEL group showed additional difference
      between the first and second minutes means temperatures. Intergroup comparison
      showed Euro-Collins solution with significant less cooling power when compared to
      all others solutions. CONCLUSION: It was possible to follow the liver cooling
      process during preservation solutions perfusion using infrared radiation images.
      Preservation solutions had similar behaviors, with Celsior(r) solution showing
      additional cooling power until the second minute of perfusion. Euro-Collins
      solution had less cooling power than other solutions studied.

PMID- 21079895
TI  - [Tacrolimus-based immunossuppresion favours liver regeneration induced by extent
      hepatectomy in rats].
AB  - OBJECTIVE: To analyze, during two different moments of liver regeneration, the
      effect of the immunosuppressant Tacrolimus on the 70% hepatectomy model-induced
      liver regeneration in adult rats. METHODS: Forty Wistar adult rats, weighing
      510.08 + 11.66 g were randomly divided into two groups, each group divided into
      two subgroups according to the death day after 70% hepatectomy . According to the
      group of study, rats received 0.1 mg/kg/day of Tacrolimus or the same volume of
      saline solution, by gavage. After three days of pre-therapy, all animals were
      submitted to 70% hepatectomy by resection of median and left lateral hepatic
      lobes which were weighed for posterior calculation of liver regeneration by
      Kwon's formula. Twenty four hours or seven days after hepatectomy ten rats of
      each group were killed; the remaining liver (regenerated) was entirely resected,
      weighed and sampled for mitotic index on hematoxylin-eosin staining and
      immunohistochemical assays with PCNA and Ki-67 markers. Data were statistically
      analyzed by Mann-Whitney or Student "t" tests, with significance level of 5%
      (p<0.05). RESULTS: Rats receiving tacrolimus showed statistically significant
      higher levels of liver regeneration when compared to placebo according to Kwon's
      formula, mitotic index and PCNA marker. Identical trend was found with Ki-67
      marker, but without statistical significance. CONCLUSION: Tacrolimus-based
      immunossuppression has stimulatory effect on liver regeneration process induced
      by 70% hepatectomy in adult Wistar rats.

PMID- 21079896
TI  - [Splenic auto-implant and hyperbaric oxygen therapy in rats].
AB  - OBJECTIVE: To study the functional and morphological features of splenic
      autoimplants in rats subjected, or not, to postoperative hyperbaric oxygen
      therapy. METHODS: One hundred and five male Wistar rats, weighing 251.6 g +/-
      29.5 g, were studied ot early (11th day) and late (70th day ) postoperative
      periods. For each period the animals were distributed in the following groups: A
      (n=40), splenic manipulation; B (n=65),splenic autoimplants, not treated (nt)
      (A11nt--n=10, B11nt--n=21, A70nt--n=10, B70nt--n=18) and treated with hyperbaric
      oxygen (t) ( A11t--n=10, B11t--n=15, A70t--n=10, B70t--n=11). Blood was collected
      for measurement of lipids and immunoglobulins, platelet and Howell-Jolly body
      count before and after surgery. The spleen and autoimplants were removed for
      histologic analyses. RESULTS: There was an increase of total cholesterol
      (p=0.00068), LDL-cholesterol (p=0.002), VLDL-cholesterol and triglycerides
      (p=0.0033) in B11nt group. There was an increase of total cholesterol (p=0.0007)
      and LDL-cholesterol (p=0.0000) in B70nt group, and no alterations were observed
      in the other groups. IgM decreased in B groups (p=0.0000) and no changes were
      observed in the splenic manipulation group. Number of Howell-Jolly bodies were
      lesser in Bt groups than in Bnt groups (p=0.03). Platelets were increased in B11t
      and B11nt groups (p=0.0000) and remained unchanged in the other groups.
      Autoimplants microscopic viability was better in Bt groups than in Bnt.
      CONCLUSION: The splenic autoimplants of rats treated with hyperbaric oxygen
      therapy showed a better functionality and viability than those subjected to other
      procedures.

PMID- 21079897
TI  - [Endoscopic aspects in the diagnosis of terminal ileum diseases].
AB  - The ileum is approximately the most distal three-fifths of the small intestine
      and is responsible for the digestion and the absorption of foods. The diagnosis
      of diseases that affects this segment can be achieved by clinical evaluation and
      complementary examinations. Not only does ileocolonoscopy allow macroscopical
      analysis, but also enables biopsies to be carried out for histological
      evaluation. Only three publications about the description of the endoscopic
      characteristics of the terminal ileum have been found in the literature. Even so,
      there have not been found descriptions or classifications in publications that
      mentioned endoscopic aspect of the terminal ileum, being reported only as normal
      ileum. Therefore, this strengthens the idea of the lack of knowledge or the non
      acceptance of these descriptions and these classifications by the scientific
      community. Endoscopic aspects of this segment when affected by several diseases
      vary from normal endoscopically ileum to cases when the macroscopical examination
      demonstrate specific features of these illnesses. In the present investigation,
      there are doubts about the need of biopsy of this segment in patients with normal
      ileoscopy. Moreover, few studies with criteria for macroscopical and
      microscopical characterization of the ileum were found.

PMID- 21079898
TI  - [Surgical education: the need of a humanistic vision].
AB  - The fragments and compartments of medical knowledge are not the only causes of
      difficulty found to form surgeons. The abandon of medical education associated
      with human science (social science) has formed professionals that understand
      biological science but don't understand life science. The distance from
      individual and cultural everyday reality enables one to not understand uniqueness
      and differences of each human being. Surgeons frequently have been described as
      someone endowed with bad qualities which actually just represent a tough and
      daring aspect. In other words, you don't need to be gifted to operate. All you
      need is effort, hard work and determination. Education built with problems
      produces a critical knowledge that makes an individual intervene in reality that
      physicians lives in a transformer, conscious and objective way. The critical and
      humanistic construction of knowledge will only be possible if teaching includes
      historical and socio-cultural characteristics and not only bio-centric and
      hospital-centric ones.

PMID- 21079899
TI  - [Clinical bioethics: how to practice?].
AB  - To think about ethics means to go into the Bioethics universe. If it is
      understood that medical ethics deals with doctors within an organized society
      under legal purposes, consensus and ethics in the exercise of medicine it is
      observed that Bioethics came up due to the need to debate and decide on the ethic
      questions related mainly to research and scientific advances as well as conquests
      concerning human rights and social-cultural development: it is the critical
      expression of our interest in conveniently using the development of medical art
      and science. Within Medicine, clinical Bioethics arouse as a possibility of
      thinking and discussing the practice of medicine in the different social
      institutions which deal with health and with professionals in health area.

PMID- 21079900
TI  - [En bloc pancreaticoduodenectomy and right hemicolectomy for locally advanced
      right colon cancer treatment].
AB  - This article reports the case of a patient with a diagnosis of diarrhea and
      weight loss. Subsidiary exams showed ulcerovegetant lesion in the second duodenal
      portion and duodenocolic fistula. An exploratory laparotomy was performed and a
      neoplastic lesion in the hepatic angle of the colon was observed invading the
      second duodenal portion. The patient then underwent a cephalic
      gastroduodenopancreatectomy associated with en bloc right hemicolectomy and
      improved well in the postoperative period. Currently, 48 months after the
      surgery, he does not present any signs of the disease dissemination or
      recurrence. The consulted literature recommends that multivisceral resection must
      be considered if the patient is clinically able to undergo major surgery and does
      not present any signs of neoplastic dissemination, since the postoperative
      survival time is considerably longer in the resected group and some of these
      patients even achieve cure.

PMID- 21079901
TI  - [Skin infections in pregnancy].
AB  - The article outlines examples of a viral (varicella-zoster virus, VZV), a
      bacterial (Lyme borreliosis) and a parasitic (scabies) infection in pregnancy
      with their risk for the mother and/or child as well as their management. VZV
      infections cause various clinical scenarios depending on the maternal immune
      status and the time of infection. Herpes zoster usually poses no risk to the
      pregnant woman and there is no need for antiviral therapy. VZV infection of a
      seronegative mother, however, may lead to severe varicella in the pregnant woman
      and to congenital malformations (congenital varicella syndrome) in case of early
      infection or neonatal varicella in case of perinatal infection. Prompt therapy
      with acyclovir or administration of VZV immunoglobulin for prophylaxis is
      mandatory in those patients. In case of Lyme borreliosis of the mother, adequate
      antibiotic therapy with amoxicillin prevents harm to the fetus. Doxycycline is
      contraindicated during pregnancy. Scabies represents an important differential
      diagnosis of pruritic dermatoses in pregnancy and should be treated with
      permethrin 5% cream.

PMID- 21079903
TI  - [A life for medicine: on the death of Professor Walter Siegenthaler (1923-2010)].

PMID- 21079902
TI  - [Dermatologic therapy in pregnancy].
AB  - Pharmacologic therapy of a pregnant patient requires particular care in selecting
      the active substances to be used, their dosage and administration. The
      teratogenic risk and the therapeutic benefit must be carefully weighed for the
      mother and possibly also for the child, and attention paid to the special
      precautions and documentation obligations of off-label applications. This article
      addresses the general aspects of benefit-risk evaluation, provides an opinion on
      the teratogenic potency of dermatologically relevant medications, formulates
      recommendations for frequent general dermatological indications and lists
      additional possible information sources for special case constellations.

PMID- 21079904
TI  - [Complications due to contrast agent administration: what has been confirmed in
      prevention?].
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) have been evaluated
      by internists to be the most important medical innovations. Often, intravenous
      contrast agent administration is required for answering the clinical questions to
      CT and MRI. In this review we present an overview of the most common and most
      important aspects that need to be considered prior to intravenous contrast agent
      administration. We discuss aspects of renal impairment (contrast-induced
      nephropathy, nephrogenic systemic fibrosis), allergy-like reactions,
      hyperthyroidism, and pregnancy and breast-feeding.

PMID- 21079905
TI  - [Treatment of not-with cystic fibrosis associated forms bronchiectasis (non-CF
      bronchiectasis)].
AB  - Bronchiectasis has become more rarely because of the development of antibiotic
      therapy and vaccination. At present the great majority of bronchiectasis is more
      likely caused by congenital disorders than by infective reasons. Therapeutic
      strategies based on the experiences from cystic fibrosis and chronic obstructive
      pulmonary disease are not always conferrable to patients suffering from
      bronchiectasis. There are not enough controlled studies to give evidence-based
      recommendations in the treatment of bronchiectasis, which are not associated with
      cystic fibrosis. Goals in the treatment are improvement of the mucociliar
      clearance, the therapy of infections and treatment of inflammation. Currently
      several agents are under examination. To improve the prognosis and therapy
      options it would be reasonable to build up a national register for patients with
      bronchiectasis.

PMID- 21079906
TI  - Hematopoietic colony-stimulating factors: new players in tumor-nerve
      interactions.
AB  - A variety of cancers are accompanied by debilitating pain, which constitutes the
      primary reason for poor quality of life in cancer patients. There is an urgent
      demand for the development of specific mechanism-based therapies against cancer
      pain. Recently, important advances have been made in mechanisms contributing to
      cancer pain. A notable finding was that the tumor-derived hematopoietic growth
      factors, granulocyte- and granulocyte-macrophage-colony-stimulating factors (G
      CSF/GM-CSF), subserve important functions in the generation of pain
      hypersensitivity in tumor-affected regions. In this context, their receptors were
      unexpectedly found on pain-sensing nerves and were observed to be functionally
      linked to nociceptive sensitization and tumor-induced pain. Here, we review
      evidence supporting a role for G-/GM-CSF in sensitization of pain-sensing nerves,
      the underlying signaling pathways and the cross-talk with other pronociceptive
      cytokines, peptides and modulators derived from immune cells, osteoclasts and
      tumor cells. These findings hold implications in the therapy of pain in disease
      states, such as cancer and rheumatoid arthritis.

PMID- 21079907
TI  - Successful TAT-mediated enzyme replacement therapy in a mouse model of
      mitochondrial E3 deficiency.
AB  - Medicine today offers no cure for patients suffering from mitochondrial
      disorders, such as lipoamide dehydrogenase (LAD; also known as E3) deficiency,
      and treatment is limited to symptomatic care. LAD is one of the components of the
      alpha-ketoacid dehydrogenase complexes, which are mitochondrial multienzyme
      complexes crucial for the metabolism of carbohydrates and amino acids. Recently,
      we tested the therapeutic approach for treating mitochondrial disorders whereby
      the activity of multicomponent complexes in the mitochondria is restored by TAT
      mediated enzyme replacement therapy (ERT). The LAD deficiency disease was used
      before as a proof-of-principle in vitro, in patients' cells, utilizing the TAT
      LAD fusion protein. In this report, we present successful TAT-mediated ERT in an
      in vivo mouse model using E3-deficient mice. We demonstrate the delivery of TAT
      LAD into E3-deficient mice tissues and that a single administration of TAT-LAD
      results in a significant increase in the enzymatic activity of the mitochondrial
      multienzyme complex pyruvate dehydrogenase complex within the liver, heart and,
      most importantly, the brain of TAT-LAD-treated E3-deficient mice. We believe that
      this TAT-mediated ERT approach could change the management of mitochondrial
      disorders and of other metabolic diseases in modern medicine.

PMID- 21079908
TI  - [Botulinum toxin in the treatment of adult spasticity. An interdisciplinary
      German 10-point consensus 2010].
AB  - Spasticity is one of the major causes of functional impairment in adults with
      lesions of the central nervous system. For instance, approximately 30% of post
      stroke patients suffer from different degrees of spasticity with possible
      consecutive impairments. Numerous studies or meta-analyses showed that local
      injections of botulinum toxin in spastic muscles lead to dose-dependent reduction
      in muscle tone and improvement of passive movements (e. g. facilitated care),
      especially following repeated injections.However, country-specific regulations
      and patient-remote administration in German health care often do not allow
      adequate provision of this therapy. Thus, the present consensus statement based
      on the EBM analyses of the published international literature tries to highlight
      recent advances and the standard in the field of local spasticity treatment,
      aiming to facilitate communication between the decision makers and German
      reimbursement institutions in health care. Prior to initiation of BoNT-A
      injections, patient-oriented goals should be identified in a multiprofessional
      context to assure realistic goals for this specific treatment and patient
      expectations. In Germany for the treatment of focal spasticity following stroke
      three products have been approved: Botox(r) (Pharm Allergan, Ettlingen),
      Dysport(r) (Ipsen Pharma, Ettlingen) and Xeomin(r) (Merz Pharma, Frankfurt/Main).
      For all preparations safety has been repeatedly shown. Functional improvements
      have also been illustrated for selected patients concerning hand/arm function and
      gait. The dose per muscle and the selection of muscles to be injected have to be
      individualized according to the patient's symptoms and should be accompanied by
      modern neurorehabilitative therapies such as redression or repetitive activation
      of the injected and antagonistic muscles.

PMID- 21079909
TI  - [Imaging aphasia].
AB  - Language is organized in a left-lateralized temporo-frontal network. This network
      organization enables the brain to reorganize language functions to compensate the
      deficit after focal brain damage, e.g. ischemic stroke. Clinically, we often
      observe a high functional dynamic in language performance within the first few
      days after stroke with a slower improvement in the further course. This suggests
      that distinct neuronal mechanisms contribute to the functional improvement during
      the different phases. This article describes how structural and functional MRI
      methods contribute to understanding loss and recovery of language functions after
      stroke. In addition, the method of pattern recognition techniques is introduced
      to demonstrate how language recovery can be predicted from early language fMRI
      data.

PMID- 21079910
TI  - [Mitoxantrone-related acute leukemia by multiple sclerosis. Case report and
      practical approach by unclear cytopenia].
AB  - BACKGROUND: Mitoxantrone is highly efficacious in the treatment of severe
      multiple sclerosis (MS). Mitoxantrone therapy-related acute leukemia (TRAL) has
      recently become the focus of interest. METHODS: A case report of fatal TRAL
      following mitoxantrone therapy is presented with a discussion on the differential
      diagnosis and risk factors. The interdisciplinary development of diagnostic and
      therapeutic algorithms is presented from a haematological and neurological point
      of view. RESULTS: We describe the case of a 34-year-old MS patient who developed
      TRAL following mitoxantrone therapy (cumulative dose 45 mg/m(2) body surface).
      The patient died from endocarditis. TRAL is a rare but potentially fatal
      complication of mitoxantrone therapy with a wide variation of reported incidence.
      Thus far, no specific risk factors relating for example to preceding therapy and
      treatment regimens have been identified. Frequent laboratory controls and early
      bone marrow aspiration are mandatory for suspected TRAL as the condition is
      potentially curable. CONCLUSIONS: TRAL needs to be considered in the risk-benefit
      assessment of mitoxantrone therapy, however, the exact incidence and risk factors
      (e.g. dosage, treatment regimen) are still unclear. The risks are controllable
      under close surveillance and early diagnosis is important for prognosis. Future
      investigations need to concentrate on identification of potential risk factors.

PMID- 21079911
TI  - Eugenics, genetics, and mental illness stigma in Chinese Americans.
AB  - BACKGROUND: The increasing interest in the genetic causes of mental disorders may
      exacerbate existing stigma if negative beliefs about a genetic illness are
      generally accepted. China's history of policy-level eugenics and genetic
      discrimination in the workplace suggests that Chinese communities will view
      genetic mental illness less favorably than mental illness with non-genetic
      causes. The aim of this study is to identify differences between Chinese
      Americans and European Americans in eugenic beliefs and stigma toward people with
      genetic mental illness. METHODS: We utilized data from a 2003 national telephone
      survey designed to measure how public perceptions of mental illness differ if the
      illness is described as genetic. The Chinese American (n = 42) and European
      American (n = 428) subsamples were analyzed to compare their support of eugenic
      belief items and measures of stigma. RESULTS: Chinese Americans endorsed all four
      eugenic statements more strongly than European Americans. Ethnicity significantly
      moderated the relationship between genetic attribution and three out of five
      stigma outcomes; however, genetic attribution actually appeared to be de
      stigmatizing for Chinese Americans while it increased stigma or made no
      difference for European Americans. CONCLUSIONS: Our findings show that while
      Chinese Americans hold more eugenic beliefs than European Americans, these
      attributions do not have the same effect on stigma as they do in Western
      cultures. These results suggest that future anti-stigma efforts must focus on
      eugenic attitudes as well as cultural beliefs for Chinese Americans, and that the
      effects of genetic attributions for mental illness should be examined relative to
      other social, moral, and religious attributions common in Chinese culture.

PMID- 21079912
TI  - Socio-economic determinants of suicide: an ecological analysis of 35 countries.
AB  - PURPOSE: A long tradition of research has shown a relationship between suicide
      rates and socio-economic factors. However, most investigations have neglected to
      account for country-specific influences. The purpose of this study was to clarify
      the association between socio-economic variables and gender-specific suicide
      rates in 35 countries, using analytic techniques able to control for effects
      embedded within different country contexts. METHOD: Data relating to male and
      female age-standardised suicide rates (obtained from the WHO Statistical
      Information System) were analysed using fixed-effect regression. The possible
      associations between suicide rates and social variables were tested using data
      for 35 countries over the period 1980-2006. RESULTS: Findings indicated that
      higher male and female suicide rates were associated with increased female labour
      force participation, unemployment, and the proportion of persons over 65 years.
      Reductions in male and female suicide rates were associated with increased health
      spending per capita. The study also revealed that higher fertility was associated
      with a reduction in male suicide. Female labour force participation had a
      stronger effect on male suicide rates. CONCLUSIONS: The results of this study
      suggest that variables related to the labour market and the economy were better
      explanatory factors of suicide rates than population-level indicators of
      interpersonal relationships. Although results were generally similar for males
      and females, males appeared to be more sensitive to changes in the social
      environment than women.

PMID- 21079913
TI  - Current-use and organochlorine pesticides and polychlorinated biphenyls in the
      biodegradable fraction of source separated household waste, compost, and
      anaerobic digest.
AB  - Several current-use (<= 80 ng g-1 dry weight) and organochlorine pesticides (<=
      15 ng g-1 dry weight) and polychlorinated biphenyls (<= 18 ng g-1 dry weight)
      were found in the biodegradable fraction of source separated household waste,
      compost, and/or anaerobic digestate. The degradation rates of individual
      compounds differ depending on the treatment. Dieldrin and pentachloroaniline,
      e.g., degrade more rapidly than the waste is mineralized and accumulates in the
      products after all treatments. Many organochlorines degrade at the same rate as
      the waste and have the same concentrations in the waste and products.
      Chlorpyrifos degrades slower than the waste and accumulates in all products and
      ethion during anaerobic digestion. The polychlorinated biphenyls and some
      pesticides show different degradations rates relative the waste during different
      processes. Understanding the degradation of the contaminants under different
      conditions is necessary to develop quality criteria for the use of compost and
      digest.

PMID- 21079914
TI  - Coprostanol in Siak River sediments, E Sumatra, Indonesia.
AB  - To follow faecal pollution steroid compounds have been analysed in 106 sediment
      samples from the Siak River, E Sumatra, Indonesia. Coprostanol was detected in 40
      of these. Contents ranged from 50 to 10,530 ng/g d.w. with a mean of 878 (TOC
      normalised: range 7.4-393.0, mean 44.1 MUg/g TOC). Total contents and the
      coprostanol/cholesterol ratio argue for a major contribution from untreated
      sewage which is also evident from field observations. The distribution along the
      river indicates the quantitatively dominant source to be the city of Pekanbaru
      with an estimated population of 1.5 million. Coprostanol contents decrease
      downstream indicating ongoing degradation either during transport or in the
      surface sediment. However, additional sources of coprostanol become evident
      further downstream. On the other hand, the 5beta/(5beta + 5alpha)-cholestan-3beta
      ol ratio versus cholesterol and a ternary plot using C27 sterols suggest that
      plant sources also contribute to the sedimentary coprostanol due to its formation
      by bacteria in suboxic/anoxic sediments.

PMID- 21079915
TI  - Tamoxifen affects the toxicokinetics of o,p'-DDT in male Nile Tilapia
      (Oreochromis niloticus).
AB  - The goal of the present study was to evaluate the role of Tamoxifen (TAM), in the
      distribution and/or elimination kinetics of o,p'-DDT, in male tilapias. A non
      compartmental analysis was chosen to describe the time course of o,p'-DDT plasma
      concentrations. Mean plasma concentration of o,p'-DDT following IP administration
      indicates a very complex kinetic profile. Tamoxifen decreased the o,p'-DDT mean
      half-life (t1/2) from 20.38 to 16.11 days, the Mean Residence Time (MRT) from
      28.7 to 23.23 days, and clearance (CL) from 0.0031 to 0.001 mL/min. The
      distribution pattern of o,p'-DDT in tissues and the clearance in plasma suggest
      that storage points mediated through the membrane-receptor lipophilicity can be
      involved.

PMID- 21079916
TI  - Simultaneous determination of acetochlor and propisochlor residues in corn and
      soil by solid phase extraction and gas chromatography with electron capture
      detection.
AB  - A sensitive and simple method for simultaneous analysis of acetochlor and
      propisochlor in corn and soil has been developed. Two herbicides were extracted
      from soil and corn matrices with methanol/water and acetone, respectively,
      followed by solid phase extraction (SPE) to remove co extractives, prior to
      analysis by gas chromatography with electron capture detection (GC-ECD). Primary
      secondary amine (PSA) SPE cartridges (500 mg, 3 mL) were used for sample
      preparation. The analytes from corn and soil matrices were eluted with 5 mL
      petroleum ether-acetic ether (95/5, v/v) and 3 mL petroleum ether-acetic ether
      (95/5, v/v), respectively. The recoveries of two pesticides ranged from 73.8% to
      115.5% with relative standard deviations (RSD) less than 11.1% and sensitivity of
      0.01 mg/kg, in agreement with directives for method validation in residue
      analysis. The method was successfully applied to determine the fate of acetochlor
      and propisochlor in real corn and soil samples. For acetochlor and propisochlor,
      the half-life times (t1/2) in soil was 5.541 and 6.074 days, respectively. No
      acetochlor and propisochlor residues (<0.01 mg/kg) were detected in corn at
      harvest time withholding period of 2.5 months after treatments of the pesticides.
      Direct confirmation of the analytes in samples was achieved by gas chromatography
      mass spectrometry (GC-MS).

PMID- 21079917
TI  - ACL injury prevention, more effective with a different way of motor learning?
AB  - PURPOSE: What happens to the transference of learning proper jump-landing
      technique in isolation when an individual is expected to perform at a competitive
      level yet tries to maintain proper jump-landing technique? This is the key
      question for researchers, physical therapists, athletic trainers and coaches
      involved in ACL injury prevention in athletes. The need for ACL injury prevention
      is clear, however, in spite of these ongoing initiatives and reported early
      successes, ACL injury rates and the associated gender disparity have not
      diminished. One problem could be the difficulties with the measurements of injury
      rates and the difficulties with the implementation of thorough large scale injury
      prevention programs. A second issue could be the transition from conscious
      awareness during training sessions on technique in the laboratory to unexpected
      and automatic movements during a training or game involves complicated motor
      control adaptations. The purpose of this paper is to highlight the issue of motor
      learning in relation to ACL injury prevention and to post suggestions for future
      research. CONCLUSION: ACL injury prevention programs addressing explicit rules
      regarding desired landing positions by emphasizing proper alignment of the hip,
      knee, and ankle are reported in the literature. This may very well be a sensible
      way, but the use of explicit strategies may be less suitable for the acquisition
      of the control of complex motor skills (Maxwell et al. J Sports Sci 18:111-120,
      2000). Sufficient literature on motor learning and it variations point in that
      direction.

PMID- 21079919
TI  - Predictors of improved overactive bladder symptoms after transvaginal mesh repair
      for the treatment of pelvic organ prolapse: predictors of improved OAB after POP
      repair.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to identify the predictors
      of improved overactive bladder (OAB) symptoms after transvaginal mesh repair.
      METHODS: Eighty women with pelvic organ prolapse (POP) stage II to IV reporting
      OAB symptoms were scheduled for transvaginal mesh procedures. Preoperative and
      postoperative assessments included a bladder diary, urodynamics, and a personal
      interview about urinary symptoms. RESULTS: Sixty-three (78.8%) women experienced
      improvement of OAB symptoms (Improvement group), and 17 (21.2%) women remained
      unchanged or worsened (Persistence group) postoperatively. A univariate analysis
      of patients' characteristics showed no difference between two groups regarding
      parity, diabetes, hypertension, prolapse status, preoperative urodynamic
      parameters, and urinary symptoms (P > 0.05). However, the age (P = 0.042) and
      preoperative detrusor overactivity (DO) (P = 0.03) were two significant
      predictors of postoperative OAB improvement. CONCLUSIONS: Women with POP may
      experience improvement of their OAB symptoms after transvaginal mesh repair. Both
      age and DO were two predictors in our univariate analysis, and the latter was the
      only significant predictor of symptom relief after adjusting age factor.

PMID- 21079918
TI  - Health-related quality of life after anterior cruciate ligament reconstruction.
AB  - PURPOSE: Recently the patients' own evaluation has become an important complement
      to post-operative clinical assessments. For many patients, there is a change in
      life situation after an anterior cruciate ligament reconstruction (ACL), which
      may affect the health-related quality of life in many ways. The aims of the study
      were to evaluate the results in terms of health-related quality of life 2-7 years
      after an ACL reconstruction and to compare the results with a gender- and age
      matched control group. Furthermore, to compare the results for males and females
      using either the bone-patellar tendon-bone autograft (BPTB) or hamstring tendon
      autograft (HT). METHODS: The SF-36 questionnaire was send by mail to 793
      consecutive patients after an ACL reconstruction. Five hundred and forty-four
      (69%) patients returned the questionnaires leaving 419 patients (161 female, 258
      male) who were analysed and matched to a Swedish control group (n = 2,410).
      RESULTS: The patient group obtained significantly higher scores for General
      Health (GH), Social Function (SF), Role Emotional (RE) and Mental Health (MH).
      The control group obtained significantly higher scores for Physical Function (PF)
      compared with the total ACL group and with the BPTB and HS subgroups. There were
      no significant differences between males and females. CONCLUSION: After ACL
      reconstruction, the patients reported good health-related quality of life in
      comparison with a matched sample of the general population. To incorporate non
      disease-specific health assessment measures are important to further refine the
      disease-specific outcome measurements to evaluate the effect of the treatments
      and provide cost-effective treatment algorithms.

PMID- 21079920
TI  - Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in
      Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate.
AB  - This study was conducted to determine the functional role of phospholipase D
      (PLD) involved in testicular Leydig cell damage caused by di (2-ethylhexyl)
      phthalate (DEHP) in Sprague-Dawley rats. DEHP (500 mg/kg/day) was administered
      orally to prepubertal rats for 1, 7, 14, 21 or 28 days. After 7 days of exposure,
      DEHP produced morphological changes in the testis, including alterations in
      seminiferous tubule diameters and loss of spermatogenic cells.
      Immunohistochemistry (IHC) analyses revealed that DEHP increased Leydig cell
      number in the testes as well as significantly increased the expression of PLD1/2
      in Leydig cells after 7 days of exposure. Furthermore, the protein levels of
      phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) increased in a
      similar manner to the PLD1/2 expression patterns. DEHP significantly reduced the
      expression of sperm-associated antigen 4 (Spag4) and lactate dehydrogenase A
      (LDHA) mRNA. In contrast, there was a significant increase in the expression of
      steroidogenic acute regulatory (StAR) mRNA against DEHP in a time-dependent
      manner, but serum testosterone concentration was decreased. These findings
      demonstrate that DEHP induces PLD expression in the testicular Leydig cells; this
      plays a key role in hyperplasia of Leydig cells and steroidogenic pathway via
      pERK1/2 activation.

PMID- 21079921
TI  - Lack of association between 71 variations located in candidate genes and response
      to acute haloperidol treatment.
AB  - RATIONALE: The antipsychotic pharmacological treatment effectiveness and side
      effects are at least partially driven by the genetic personal background.
      OBJECTIVES: In the present study, 71 genetic variations located in 21 candidate
      genes were investigated as modulators of the haloperidol efficacy and side
      effects in a sample of 101 acutely ill psychotic patients. METHODS: Patients were
      assessed at days 0, 7, 14, 21, and 28 (Positive and Negative Syndrome Scale
      (PANSS) test) and days 1, 3, 7, 14, 21, and 28 (UKU, BAS, and ESRS tests).
      Haloperidol plasma levels were measured at the same timepoints. RESULTS: None of
      the 71 variations were associated with response to treatment or with incidence of
      side effects passed a multiple testing threshold. A marginal association was
      detected between two haplotypes within the signal transducer and activator of
      transcription 4 gene and PANSS positive and dopamine beta-hydroxylase with PANSS
      negative scores (p = 0.004 and p = 0.008, respectively). CONCLUSIONS: In
      conclusion, no major association was observed between the investigated variations
      and the efficacy profile of haloperidol.

PMID- 21079922
TI  - Inhibitory effects of alcohol on glucose transport across the blood-brain barrier
      leads to neurodegeneration: preventive role of acetyl-L: -carnitine.
AB  - PURPOSE: Evidence shows that alcohol intake causes oxidative neuronal injury and
      neurocognitive deficits that are distinct from the classical Wernicke-Korsakoff
      neuropathy. Our previous findings indicated that alcohol-elicited blood-brain
      barrier (BBB) damage leads to neuroinflammation and neuronal loss. The dynamic
      function of the BBB requires a constant supply and utilization of glucose. Here
      we examined whether interference of glucose uptake and transport at the
      endothelium by alcohol leads to BBB dysfunction and neuronal degeneration.
      MATERIAL AND METHODS: We tested the hypothesis in cell culture of human brain
      endothelial cells, neurons and alcohol intake in animal by immunofluorescence,
      Western blotting and glucose uptake assay methods. RESULTS: We found that
      decrease in glucose uptake correlates the reduction of glucose transporter
      protein 1 (GLUT1) in cell culture after 50 mM ethanol exposure. Decrease in GLUT1
      protein levels was regulated at the translation process. In animal, chronic
      alcohol intake suppresses the transport of glucose into the frontal and occipital
      regions of the brain. This finding is validated by a marked decrease in GLUT1
      protein expression in brain microvessel (the BBB). In parallel, alcohol intake
      impairs the BBB tight junction proteins occludin, zonula occludens-1, and claudin
      5 in the brain microvessel. Permeability of sodium fluorescein and Evans Blue
      confirms the leakiness of the BBB. Further, depletion of trans-endothelial
      electrical resistance of the cell monolayer supports the disruption of BBB
      integrity. Administration of acetyl-L: -carnitine (a neuroprotective agent)
      significantly prevents the adverse effects of alcohol on glucose uptake, BBB
      damage and neuronal degeneration. CONCLUSION: These findings suggest that alcohol
      elicited inhibition of glucose transport at the blood-brain interface leads to
      BBB malfunction and neurological complications.

PMID- 21079924
TI  - Applicability of a yeast bioassay in the detection of steroid esters in hair.
AB  - The aim of the present study was to demonstrate the applicability of a yeast
      androgen and estrogen bioassay in the detection of steroid esters in hair samples
      of animals treated with a hormone ester cocktail. The outcome of the activity
      screenings was critically compared with the results previously obtained with LC
      MS/MS analysis. Hair samples of one pour-on treated animal, 10 ml DMSO containing
      25 mg estradiol benzoate (EB), 60 mg testosterone decanoate (TD) and 60 mg
      testosterone cypionate (TC), were selected and analyzed with the androgen and
      estrogen yeast bioassay. Results showed that by the introduction of a hydrolysis
      step, bioassays can be used to screen for the presence of hormone esters in hair
      samples. Based on the difference in fluorescence responses between the non
      hydrolyzed and the hydrolyzed hair samples, it was possible to detect the
      presence of EB up to at least 56 days after a single pour-on treatment and to
      detect the presence of TC and TD up to at least 14 days after the treatment.
      Although the LC-MS/MS analysis could detect TC and TD up to 49 days after
      treatment, bioassays have the advantage that they can also detect any (un)known
      steroid ester.

PMID- 21079925
TI  - Automated targeting analysis of eicosanoid inflammation biomarkers in human serum
      and in the exometabolome of stem cells by SPE-LC-MS/MS.
AB  - Inflammation is a complex cascade process involved in the pathogenesis of a
      number of diseases or generated as response to external or internal stimuli.
      Current research is focused on the development of assays for fast identification
      and quantitation of inflammation biomarkers. Eicosanoids are the oxidation
      metabolites of polyunsaturated fatty acids (mainly 20-carbon fatty acids) that
      play a regulation role in inflammation and, therefore, they have proved to be
      involved in different pathological states such as cancer, atherosclerosis,
      arthritis and cardiovascular or immunological diseases. Eicosanoids can be
      metabolized by different oxygenase enzymes to prostanoids such as prostaglandins
      and thromboxanes or hydroxyl fatty acids such as hydroxyeicosatetraenoic acids
      and hydroxyoctadecadienoic acids. A high-throughput automated approach is here
      presented for direct eicosanoid analysis in biofluids such as human serum and
      cells culture media. The approach is based on a hyphenated system composed by a
      solid-phase extraction workstation (Prospekt 2 unit) on-line coupled to a liquid
      chromatograph-triple quadrupole-tandem mass spectrometer. The detection limits
      for the target analytes ranged from 0.009 to 204 pg on-column, with precision
      between 2.65% and 7.33%, expressed as relative standard deviation. Accuracy
      studies with a dual-cartridge configuration resulted in recoveries between 78.6%
      and 100%, which validated internally the proposed approach ensuring highly
      efficient cleanup of proteins and salts. The method is reliable, robust and
      endowed with a great potential for implementation in clinical and routine
      laboratories. Analysis of culture media of stem cells stimulated with arachidonic
      acid was carried out to evaluate its incidence on the eicosanoid profile of the
      exometabolome.

PMID- 21079926
TI  - Development of the first metabolite-based LC-MS(n) urine drug screening procedure
      exemplified for antidepressants.
AB  - In contrast to GC-MS libraries, currently available LC-MS libraries for
      toxicological detection contain besides parent drugs only some main metabolites
      limiting their applicability for urine screening. Therefore, a metabolite-based
      LC-MS(n) screening procedure was developed and exemplified for antidepressants.
      The library was built up with MS(2) and MS(3) wideband spectra using an LXQ
      linear ion trap with electrospray ionization in the positive mode and full-scan
      information-dependent acquisition. Pure substance spectra were recorded in
      methanolic solution and metabolite spectra in urine from rats after
      administration of the corresponding drugs. After identification, the metabolite
      spectra were added to the library. Various drugs and metabolites could be
      sufficiently separated. Recovery, process efficiency, matrix effects, and limits
      of detection for selected drugs were determined using protein precipitation.
      Automatic data evaluation was performed using ToxID and SmileMS software. The
      library consists of over 700 parent compounds including 45 antidepressants, over
      1,600 metabolites, and artifacts. Protein precipitation led to sufficient results
      for sample preparation. ToxID and SmileMS were both suitable for target screening
      with some pros and cons. In our study, only SmileMS was suitable for untargeted
      screening being not limited to precursor selection. The LC-MS(n) method was
      suitable for urine screening as exemplified for antidepressants. It also allowed
      detecting unknown compounds based on known fragment structures. As ion
      suppression can never be excluded, it is advantageous to have several targets per
      drug. Furthermore, the detection of metabolites confirms the body passage. The
      presented LC-MS(n) method complements established GC-MS or LC-MS procedures in
      the authors' lab.

PMID- 21079923
TI  - Blockade of 5-HT2A receptors in the medial prefrontal cortex attenuates
      reinstatement of cue-elicited cocaine-seeking behavior in rats.
AB  - RATIONALE: The action of serotonin (5-HT) at the 5-HT(2A) receptor subtype is
      thought to be involved in cocaine-seeking behavior that is motivated by exposure
      to drug-associated cues and drug priming. 5-HT(2A) receptors are densely
      clustered in the ventromedial prefrontal cortex (vmPFC), an area that plays a
      role in mediating cocaine-seeking behavior. OBJECTIVES: This study examined the
      hypothesis that M100907, a 5-HT(2A) receptor antagonist, infused directly in the
      vmPFC attenuates cue- and cocaine-primed reinstatement of cocaine-seeking
      behavior. METHODS: Rats trained to self-administer cocaine (0.75 mg/kg, i.v.)
      paired with light and tone cues underwent extinction training during which
      operant responses produced no consequences. Once behavior extinguished, rats were
      tested for reinstatement of responding elicited by either response-contingent
      presentations of the cocaine-paired light/tone cues or by cocaine-priming
      injections (10 mg/kg, i.p.) within 1 min after pretreatment with microinfusions
      of M100907 (0.1, 0.3, 1.0, or 1.5 MUg/0.2 MUl/side) into the vmPFC. RESULTS:
      Intra-vmPFC M100907 decreased cue-elicited reinstatement at the two highest doses
      (1.0 and 1.5 MUg) but produced only a slight decrease in cocaine-primed
      reinstatement that was not dose dependent. The decrease in cue reinstatement was
      not likely due to impaired ability to respond since intra-vmPFC M100907 infusions
      had minimal effect on cocaine self-administration and no effect on cue-elicited
      sucrose-seeking behavior, or spontaneous or cocaine-induced locomotion. M100907
      infusions into the adjacent anterior cingulate cortex had no effect on cue
      reinstatement. CONCLUSIONS: The results suggest that the blockade of 5-HT(2A)
      receptors in the vmPFC selectively attenuates the incentive motivational effects
      of cocaine-paired cues.

PMID- 21079927
TI  - In-column "click" preparation of hydrophobic organic monolithic stationary phases
      for protein separation.
AB  - Two types of macroporous organic polymer monoliths based on glycidyl methacrylate
      (GMA), 4-vinylbenzyl chloride (VBC) and divinylbenzene (DVB) were prepared inside
      stainless-steel tubes. Azide functionalities were firstly introduced on the
      surfaces of poly(GMA-co-DVB) and poly(VBC-co-DVB) monoliths to provide reactive
      sites for click chemistry. With the application of copper(I)-catalyzed (3 + 2)
      azide-alkyne cycloaddition, an in-column click-modification approach for covalent
      attachment of long alkyl chains onto polymer monoliths was developed. The column
      morphology and surface chemistry of the fabricated monolithic columns were
      characterized by the scanning electron microscopy, mercury intrusion porosimeter,
      Fourier transform infrared spectroscopy, and elemental analyses, respectively.
      The chromatographic performances of the "clicked" stationary phases were
      demonstrated with the high separation efficiency for a variety of proteins within
      4 min.

PMID- 21079929
TI  - An improved method of protein localization in artworks through SERS nanotag
      complexed antibodies.
AB  - There are several analytical techniques currently in use in conservation science
      to identify proteins in artworks. However, as is often the case, the
      determination of the exact location of a protein in a complex layer structure is
      challenging due to difficulty in separating layers. Localization of the protein
      in a cross-section has been demonstrated through attenuated total reflectance
      Fourier transform infrared mapping and imaging as well as chemiluminescent and
      fluorescent-labeled antibodies; however, these techniques either require
      expensive instrumental setups or produce results that can be challenging to
      interpret. This paper will present research using surface-enhanced Raman
      scattering (SERS) nanotags complexed to secondary antibodies in conjunction with
      primary antibodies for the localization of ovalbumin, collagen, and casein in
      cross-sections from replicas and artworks containing avian egg, animal glue, or
      casein binders. The advantages of this technique over the others are (1) the
      detection method is a Raman microscope, equipment found in several museum
      laboratories; (2) the distinctive SERS signal from the nanotag increases the
      detection limit of the protein and decreases the interference from other
      colorants present in the cross-section layers; and finally, (3) the large (120
      nm) SERS-labeled antibodies do not appear to penetrate into the cross-section,
      eliminating the risk of spurious signal and misidentification. Any agglomerations
      due to surface texture are clearly visible under normal illumination and can be
      avoided easily during analysis or removed with a light polish. This technique not
      only allows protein localization in multilayered samples while preserving the
      stratigraphic information but also retains the protein specificity of the
      antibody approach.

PMID- 21079928
TI  - Ionic liquid 1-butyl-3-methyl imidazolium tetrafluoroborate for shotgun membrane
      proteomics.
AB  - The solubility and digestion efficiency are two crucial factors that might affect
      the identification of integral membrane proteins (IMPs). In this work, 1% (v/v)
      ionic liquid (IL), 1-butyl-3-methyl imidazolium tetrafluoroborate (BMIM BF(4)),
      added in NH(4)HCO(3) buffer (pH 8.3), was applied as a sample preparation buffer
      for IMPs analysis. Compared to the commonly used sodium dodecyl sulfate and
      methanol methods, the number of identified IMPs from rat brain by microcolumn
      reversed phase liquid chromatography (MURPLC)-electrospray ionization tandem mass
      spectrometry (ESI-MS/MS) was improved by over three times, which might be due to
      the fact that BMIM BF(4) offered high solubilizing ability for IMPs and good
      compatibility for tryptic digestion. Furthermore, compared to Rapigest and urea
      methods, with BMIM BF(4) method, the number of identified IMPs from rat brain
      could be improved 25% and 80%, respectively, which might be contributed to the
      good solubilizing ability and high thermal stability of such IL. With the sample
      treated by BMIM BF(4) method, by 2D-nanoSCX-RPLC-ESI-MS/MS, 1,450 non-redundant
      proteins and 7,978 unique peptides were identified from rat brain, and 418
      proteins contained at least one predicted transmembrane domain, with false
      discovery rates of less than 1% for peptide identification, and at least two
      identified unique peptides per protein. All these results demonstrate that the
      BMIM BF(4) method is of high potential for the large-scale identification of
      IMPs.

PMID- 21079930
TI  - Position-resolved determination of trace elements in mandibular gnathobases of
      the Antarctic copepod Calanoides acutus using a multimethod approach.
AB  - Previous studies have revealed silica formation in the teeth of mandibular
      gnathobases of copepods while significant amounts of zinc and copper are present,
      which might improve mechanical stability of the teeth and represent an adaptation
      to compact food particles. The present study aimed at analysing the distribution
      and concentration of trace elements in the mandibular gnathobases of females of
      the Antarctic copepod species Calanoides acutus. Because of the low overall
      masses of few micrograms per specimen the application of a combination of
      position-resolved micro-beam techniques was necessary and micro-particle-induced
      X-ray emission spectrometry and laser ablation inductively coupled plasma mass
      spectrometry were used to determine Ba, Br, Ca, Cl, Cu, Fe, K, Mg, Na, Ni, P, S,
      Si and Zn in the samples with MUm to sub-MUm resolution. Calibration strategies
      were optimised to fit for the carbonate matrix. The analyses revealed a distinct
      enrichment of Br, Ca, Fe, K, S, Si and Zn in the teeth of the gnathobases.

PMID- 21079931
TI  - SR-XRD and SR-FTIR study of the alteration of silver foils in medieval paintings.
AB  - Altarpieces and polychrome carved wood from the fifteenth century AD usually
      exhibit golden and silvery areas by the application of a very thin foil of metal.
      The metal foils were normally protected from the atmosphere by a varnish or resin
      which maybe either preserved or absent. Moreover, they were glued to the
      background surface by adhesive substances (egg yolk, drying oil or animal glue).
      The high proportion of the glueing substances often renders the development of
      reaction compounds. With time, silver alters blacken or simply disappear
      completely. In this paper, we study the alterations to metal foils from a
      selection of fifteenth century artworks showing different glueing agents, organic
      coatings and several degrees of conservation of the organic coatings and metal
      leafs. The submillimetric layered structure and the high variability and low
      amount of most of the compounds present in the different layers, as well as their
      differing nature (organic and inorganic) make the use of micron-sensitive high
      resolution techniques essential for their study. In particular, the high
      resolution, high brilliance and small footprint renders synchrotron radiation
      most adequate for their study. SR-XRD was performed to identify the reaction
      compounds formed in the different layers; MUFTIR was used at to identify the
      silver protecting organic coatings, the metal foil glueing layers and the
      corresponding reaction compounds. The results obtained suggest that atmospheric
      corrosion is the dominant mechanism, and therefore that the degree of corrosion
      of the metal foils is mainly related to the conservation state of the protecting
      coatings.

PMID- 21079932
TI  - LC-MS-MS determination of ibuprofen, 2-hydroxyibuprofen enantiomers, and
      carboxyibuprofen stereoisomers for application in biotransformation studies
      employing endophytic fungi.
AB  - The purpose of this study was the development and validation of an LC-MS-MS
      method for simultaneous analysis of ibuprofen (IBP), 2-hydroxyibuprofen (2-OH
      IBP) enantiomers, and carboxyibuprofen (COOH-IBP) stereoisomers in fungi culture
      medium, to investigate the ability of some endophytic fungi to biotransform the
      chiral drug IBP into its metabolites. Resolution of IBP and the stereoisomers of
      its main metabolites was achieved by use of a Chiralpak AS-H column (150 * 4.6
      mm, 5 MUm particle size), column temperature 8  degrees C, and the mobile phase
      hexane-isopropanol-trifluoroacetic acid (95: 5: 0.1, v/v) at a flow rate of 1.2
      mL min(-1). Post-column infusion with 10 mmol L(-1) ammonium acetate in methanol
      at a flow rate of 0.3 mL min(-1) was performed to enhance MS detection (positive
      electrospray ionization). Liquid-liquid extraction was used for sample
      preparation with hexane-ethyl acetate (1:1, v/v) as extraction solvent. Linearity
      was obtained in the range 0.1-20 MUg mL(-1) for IBP, 0.05-7.5 MUg mL(-1) for each
      2-OH-IBP enantiomer, and 0.025-5.0 MUg mL(-1) for each COOH-IBP stereoisomer (r
      >= 0.99). The coefficients of variation and relative errors obtained in precision
      and accuracy studies (within-day and between-day) were below 15%. The stability
      studies showed that the samples were stable (p > 0.05) during freeze and thaw
      cycles, short-term exposure to room temperature, storage at -20  degrees C, and
      biotransformation conditions. Among the six fungi studied, only the strains
      Nigrospora sphaerica (SS67) and Chaetomium globosum (VR10) biotransformed IBP
      enantioselectively, with greater formation of the metabolite (+)-(S)-2-OH-IBP.
      Formation of the COOH-IBP stereoisomers, which involves hydroxylation at C3 and
      further oxidation to form the carboxyl group, was not observed.

PMID- 21079933
TI  - Fluorescence and Fourier-transform infrared spectroscopy for the analysis of
      iconic Italian design lamps made of polymeric materials.
AB  - The preservation of design object collections requires an understanding of their
      constituent materials which are often polymeric blends. Challenges associated
      with aging of complex polymers from objects with an unknown physical history may
      compromise the interpretation of data from analytical techniques, and therefore
      complicate the assessment of the condition of polymers in indoor museum
      environments. This study focuses on the analysis of polymeric materials from
      three well-known Italian design lamps from the 1960s. To assess the degree of
      chemical modifications in the polymers, non-destructive molecular spectroscopic
      techniques, Fourier-transform infrared (FTIR) and fluorescence spectroscopy, have
      been applied directly on the object surfaces using an optical fiber probe and
      through examination of micro samples. FTIR spectra of the different polymers,
      polyvinylacetate (PVAc) for the lamps Taraxacum and Fantasma, and both
      acrylonitrile-butadiene-styrene polymer (ABS) and cellulose acetate (CA) for the
      lamp Nesso, allowed the detection of ongoing deterioration processes.
      Fluorescence spectroscopy proved particularly sensitive for the detection of
      molecular changes in the polymeric objects, as the spectra obtained from the
      examined lamps differ significantly from those of the unaged reference materials.
      Differences in fluorescence spectra are also detected between different points on
      the same object further indicating the presence of different chemical species on
      the surfaces. With the aid of complementary data from FTIR spectroscopy, an
      interpretation of the emission spectra of the studied polymeric objects is here
      proposed, further suggesting that fluorescence spectroscopy may be useful for
      following the degradation of historical polymeric objects.

PMID- 21079934
TI  - Adverse events following immunization in children: retrospective analysis of
      spontaneous reports over a decade.
AB  - PURPOSE: There is no doubt that paediatric immunization prevents serious
      diseases, but the administration of these vaccines to healthy children also
      involves risks of adverse drug reactions (ADRs), some of which are potentially
      serious. The current body of evidence on ADRs from immunization therapy at the
      population level is partly contradictory across countries, time periods and
      childhood immunization programmes. The objective of our study was to characterize
      reported adverse events (AEFIs) following immunization in Danish children.
      METHODS: Adverse events (AEFIs) in 0- to 17-year-old children and adolescents
      reported to the Danish Medicines Agency (DKMA) between 1998 and 2007 were
      analysed. The unit of analysis was one AEFI. Data were categorized with respect
      to time, age, and gender of the children, suspected vaccines, category and
      seriousness of the AEFIs, and reporting rate. RESULTS: During the study period,
      the DKMA received 1,365 reports covering 2,600 AEFIs, corresponding to 60% of all
      adverse events reported for children. One third of the AEFIs were classified as
      serious, and two deaths were reported. The annual number of serious AEFIs
      remained constant during the study period. Approximately 80% of AEFIs were
      reported in children aged 0-2 years. Of all reported AEs, 45% were in the
      category "general disorders and administration site conditions", followed by the
      categories "skin and subcutaneous tissue disorders" (20% of total AEFIs) and
      "nervous system disorders" (16% of total AEFIs). The largest share of serious
      events was from the category "nervous system disorders" (33% of serious AEFIs).
      The most frequently reported serious AEs were febrile convulsions, pyrexia, and
      injection-site reactions. CONCLUSIONS: In Denmark, a large number of AEFIs
      following paediatric immunization have been reported, but the majority of cases
      were non-serious.

PMID- 21079935
TI  - CYP2C19-guided design of a proton pump inhibitor dose regimen to avoid the need
      for pharmacogenetic individualization in H. pylori eradication.
AB  - OBJECTIVE: It has been demonstrated that genetic variation in CYP2C19 has a
      significant influence upon H. pylori eradication rates. We have determined a
      dosage regimen of lansoprazole that will provide EMs with exposure approximately
      equivalent to that obtained by PMs treated with standard doses and determined the
      exposure that a PM would experience if they were to be treated with this 'EM
      optimised' lansoprazole dose. METHODS: Non-compartmental pharmacokinetic
      parameters (AUC, C(max), t(max)) for CYP2C19 genotypes were obtained from the
      literature. Primary pharmacokinetic parameters (CL, Vd, ka) for 200 virtual
      patients were calculated from the weighted non-compartmental variables and used
      to simulate a 7 day treatment course of twice daily lansoprazole, at standard and
      optimised doses for 1,000 patients. RESULTS: The administration of 180 mg twice
      daily to CYP2C19 EMs results in approximately equivalent exposure to lansoprazole
      as the administration of standard 30 mg twice daily doses to PMs. Administration
      of this six-fold dose increase to EMs is predicted to result in only a 2.5-fold
      increase in C(max) when compared with PMs receiving the standard 30 mg dose.
      CONCLUSION: We present a potential lansoprazole dosing regimen that should result
      in improved H. pylori eradication within CYP2C19 EMs and may not require
      individualization. Whilst the optimised dose represents a significant increase,
      it is below that reported in the chronic management of Zollinger-Ellison
      syndrome. On the basis that treatment is of limited duration and lansoprazole is
      generally well tolerated, such an approach warrants further in vivo evaluation to
      confirm drug exposure, efficacy and tolerability.

PMID- 21079936
TI  - Flip-flop kinetics of ropivacaine during continuous epidural infusion influences
      its accumulation rate.
AB  - BACKGROUND: Ropivacaine has an optimal toxicity profile for epidural anesthesia
      in adults, but there are currently no studies concerning its pharmacokinetics
      during continuous infusion. The primary objective of this study was to evaluate
      the pharmacokinetics and safety of ropivacaine in adults during a 48-h continuous
      epidural infusion. MATERIALS AND METHODS: We enrolled 43 adults (ASA I-II)
      scheduled for major abdominal or urologic surgery with postoperative continuous
      epidural analgesia with ropivacaine 0.2% (5 mL/h) and sufentanil 0.75 MUg/mL for
      48 h. Ropivacaine blood samples were collected during continuous epidural
      infusion before the bolus and 3, 6, 12, 24, 48, 54, 60 h after the bolus; plasma
      concentrations were measured on HPLC-UV. The concentration-time relationship of
      ropivacaine levels was analyzed using a population pharmacokinetic method based
      on a mixed-effect-model approach (P-PHARM software). RESULTS: Mean plasma
      concentration of ropivacaine at the end of epidural infusion (C(48 h)) was 1.69
      MUg/mL (0.21-3.8 MUg/mL). Mean (range) C(max) was 1.82 MUg/mL (0.61-4.0 MUg/mL);
      the area under the plasma concentration curve, AUC ((0-60)), was 67.48 +/- 30.60
      MUg.h/mL. Total plasma ropivacaine concentrations fell mainly within (84%) or
      below (12%) the range reported to be safe in adults (1.0-3.0 MUg/mL). Only two
      patients (5%) reached ropivacaine plasma levels higher than 3 MUg/mL, namely 3.8
      and 4.0 MUg/mL at 48 and 54 h, respectively. Total ropivacaine concentrations up
      to 4.0 MUg/mL were tolerated during long-term epidural ropivacaine infusion. Mean
      clearance for total ropivacaine was 5.33 L/h. Age was the only covariable to
      significantly reduce clearance variability: CL (L/h)=15.04-0.148 * age (years).
      The volume of distribution (Vd) was 92.15 L. The infusion dosing period half-life
      (t(1/2,DP)=0.693 * Vd/CL) was 10.8 h. CONCLUSIONS: Exposure to ropivacaine during
      epidural infusion is highly variable. The apparent infusion dosing half-life
      t(1/2,DP) is the most appropriate parameter to predict drug accumulation upon
      epidural infusion since it appears to better reflect the interplay interference
      between volume distribution and absorption rate during the accumulation phase.
      Prediction of ropivacaine accumulation can be improved by considering patient
      age.

PMID- 21079938
TI  - Formation of macromolecule complex with Bacillus thuringiensis Cry1A toxins and
      chlorophyllide binding 252-kDa lipocalin-like protein locating on Bombyx mori
      midgut membrane.
AB  - P252, a 252-kDa Bombyx mori protein located on the larval midgut membrane, has
      been shown to bind strongly with Bacillus thuringiensis Cry1A toxins (Hossain et
      al. Appl Environ Microbiol 70:4604-4612, 2004). P252 was also shown to bind
      chlorophyllide (Chlide) to form red fluorescence-emitting complex Bm252RFP with
      significant antimicrobial activity (Pandian et al. Appl Environ Microbiol 74:1324
      1331, 2008). In this article, we show that Cry1A toxin bound with Bm252RFP and
      Bm252RFP-Cry1A macrocomplex, with both antimicrobial and insecticidal activities,
      was formed. The insecticidal activity of Bm252RFP-Cry1Ab was reduced from an LD50
      of 1.62 to 5.05 MUg, but Bm252RFP-Cry1Aa and Bm252RFP-Cry1Ac did not show such
      reduction. On the other hand, the antimicrobial activity of Bm252RFP-Cry1Ab was
      shown to retain almost the same activity as Bm252RFP, while the other two
      complexes lost around 30% activity. The intensity of photo absorbance and
      fluorescence emission of Bm252RFP-Cry1Ab were significantly reduced compared to
      those of the other two complexes. Circular dichroism showed that the contents of
      Cry1Ab alpha-helix was significantly decreased in Bm252RFP-Cry1Ab but not in the
      other two toxins. These data suggested that the reduction of contents of alpha
      helix in Cry1Ab affected the insecticidal activity of the macrocomplex but did
      not alter the antimicrobial moiety in the macrocomplex of Bm252RFP-Cry1Ab.

PMID- 21079937
TI  - Different effects of tocolytic medication on blood pressure and blood pressure
      amplification.
AB  - BACKGROUND: The importance of tocolysis has been discussed extensively. Beta-2
      adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic
      drugs in most countries. Cardiovascular side-effects are frequent. Atosiban, a
      newer tocolytic drug, is a competitive antagonist of oxytocin and has fewer
      cardiovascular side effects. Although large studies exist, there is mainly
      subjective reporting of adverse reactions with a focus on blood pressure data.
      OBJECTIVES: Evaluation of the acute effects of therapeutic doses of ritodrine and
      atosiban in comparison to placebo on central and peripheral blood pressures,
      central-to-peripheral blood pressure amplification and the augmentation index
      (AIx) in healthy non-pregnant female volunteers. METHODS: A double-blind,
      randomized, crossover trial was carried out in 20 healthy non-pregnant female
      volunteers. Hemodynamic measurements were performed under standardized
      conditions. RESULTS: At steady state, central and peripheral pressures did not
      differ from placebo in the atosiban group. During ritodrine -infusion, central
      SBP increased by 11% versus placebo (p = 0.012) and peripheral SBP by 10% (p =
      0.004). In contrast to atosiban and placebo, blood pressure amplification was
      absent in the ritodrine group. While the AIx did not change in the atosiban
      group, with ritodrine, the AIx tended to decrease. CONCLUSIONS: The present study
      shows the significant effects of ritodrine on the cardiovascular system. Atosiban
      has no significant effects and may be an appropriate alternative to tocolyticum,
      particularly in cardiovascularly complicated pregnancies.

PMID- 21079939
TI  - The last universal common ancestor (LUCA) and the ancestors of archaea and
      bacteria were progenotes.
AB  - The tRNA split genes of Nanoarchaeum equitans and the Met-tRNA(fMet) -> fMet
      tRNA(fMet) pathway, identifiable as ancestral traits, and the late appearance of
      DNA are used to understand the evolutionary stage at which the progenote ->
      genote transition took place. The arguments are such as to impose that not only
      was the last universal common ancestor (LUCA) a progenote, but the ancestors of
      Archaea and Bacteria were too. Therefore, the progenote -> genote transition took
      place in a very advanced stage of the evolution of the tree of life, and only
      when the ancestors of Archaea and Bacteria were already defined. These
      conclusions are in disagreement with commonly held beliefs.

PMID- 21079941
TI  - Eisenmenger ventricular septal defect: classification, morphology, and
      indications for surgery.
AB  - This study aimed to examine the definition and indications for surgery, to
      elucidate the morphologic substrate of aortic regurgitation, and to extrapolate
      the pathologic mechanisms of subpulmonary stenosis in Eisenmenger ventricular
      septal defect (EVSD). The study enrolled 160 patients. Preoperative respiratory
      symptoms and poor growth were present in 41 patients (26%), and 21 patients (13%)
      required mechanical ventilation. Perimembranous ventricular septal defect (pVSD)
      had been diagnosed previously for 136 of the patients (85%) at other
      institutions. Of the 160 patients, 51 (32%) had muscular posteroinferior rims.
      Aortic regurgitation was experienced by 36 patients (23%), found to be mild in 31
      cases (19%) and moderate in 5 cases (3%). None of the patients had severe
      regurgitation. No aortic valvuloplasty was performed. The significant risk
      factors for aortic regurgitation were subpulmonary stenosis (p = 0.001) and a
      muscular posteroinferior rim (p = 0.000). Subpulmonary stenosis was seen in 57
      patients (35%), found to be mild to moderate in 42 cases (26%) and severe in 15
      cases (9%). Adequacy of the stenosis band was repaired through the tricuspid
      valve for 57 of these patients. The definition of EVSD should identify it as a
      subgroup different from pVSD, and it should be closed as soon as it is identified
      in developing countries. Aortic regurgitation occurs rarely, and aortic
      valvoplasty should be performed if it exceeds a moderate level. The subpulmonary
      stenosis can be repaired through the tricuspid valve.

PMID- 21079940
TI  - Male sex interspecies divergence and down regulation of expression of
      spermatogenesis genes in Drosophila sterile hybrids.
AB  - Male sex genes have shown a pattern of rapid interspecies divergence at both the
      coding and gene expression level. A common outcome from crosses between closely
      related species is hybrid male sterility. Phenotypic and genetic studies in
      Drosophila sterile hybrid males have shown that spermatogenesis arrest is
      postmeiotic with few exceptions, and that most misregulated genes are involved in
      late stages of spermatogenesis. Comparative studies of gene regulation in sterile
      hybrids and parental species have mainly used microarrays providing a whole
      genome representation of regulatory problems in sterile hybrids. Real-time PCR
      studies can reject or reveal differences not observed in microarray assays.
      Moreover, differences in gene expression between samples can be dependant on the
      source of RNA (e.g., whole body vs. tissue). Here we survey expression in D.
      simulans, D. mauritiana and both intra and interspecies hybrids using a real-time
      PCR approach for eight genes expressed at the four main stages of sperm
      development. We find that all genes show a trend toward under expression in the
      testes of sterile hybrids relative to parental species with only the two
      proliferation genes (bam and bgcn) and the two meiotic class genes (can and sa)
      showing significant down regulation. The observed pattern of down regulation for
      the genes tested can not fully explain hybrid male sterility. We discuss the down
      regulation of spermatogenesis genes in hybrids between closely-related species
      within the contest of rapid divergence experienced by the male genome, hybrid
      sterility and possible allometric changes due to subtle testes-specific
      developmental abnormalities.

PMID- 21079942
TI  - Borderline low conus medullaris on infant lumbar sonography: what is the clinical
      outcome and the role of neuroimaging follow-up?
AB  - BACKGROUND: Isolated borderline low conus medullaris is a frequent finding on
      screening lumbar sonography of unknown significance that often prompts further
      imaging and clinical follow-up. OBJECTIVE: To determine the clinical outcome and
      utility of follow-up neuroimaging in infants with isolated borderline low conus
      on lumbar sonography. MATERIALS AND METHODS: We reviewed 748 consecutive spinal
      sonograms identifying infants with conus terminating between L2-L3 disc space and
      mid-L3 level without other findings of tethered cord. We excluded infants with
      conditions associated with developmental delay and those who passed away, and
      compared the age of gross motor milestone achievement to normal ranges. Follow-up
      imaging was reviewed. RESULTS: Isolated borderline low conus was found in 90 of
      748 infants (12%) on sonography. Seventy of those infants met inclusion criteria.
      Follow-up imaging in 11 children (10 MRI, 1 sonogram), showed change in conus
      position to "normal" level in 10, no change in 1, and no new findings within
      lumbar spine. Clinical follow-up was available in 50 of 70 (71%) children meeting
      inclusion criteria, with normal motor milestones met in all 50 children.
      CONCLUSION: Isolated borderline low conus is a common finding in infants who meet
      normal developmental milestones suggesting that follow-up evaluation has little
      utility and is likely unwarranted.

PMID- 21079943
TI  - Developing low-dose C-arm CT imaging for temporomandibular joint (TMJ) disorder
      in interventional radiology.
AB  - BACKGROUND: Manufacturers have provided C-arm CT imaging technologies for
      applications in interventional radiology in recent years. However, clinical
      imaging protocols and radiation doses have not been well studied or reported.
      OBJECTIVE: The purpose of this study is to develop low-dose settings for
      clinically acceptable CT imaging of temporomandibular joint in interventional
      radiology suites, using a C-arm imaging angiography system. MATERIALS AND
      METHODS: CT scans were performed with a flat-panel digital C-arm angiographic
      system on a 5-year-old anthropomorphic phantom. The CTDI was determined for
      various rotation times, dose settings and Cu filter selections. The CTDI values
      were compared with those of conventional low-dose CT for the same phantom. The
      effectiveness of using Cu filters to reduce dose was also investigated. Images
      were reviewed by a senior radiologist for clinical acceptance. RESULTS: The
      manufacturer's default setting gave an equivalent CTDI of 4.8 mGy. Optimizing the
      dose settings and adding copper filtration reduced the radiation dose by 94%.
      This represents a 50% reduction from conventional CT. CONCLUSION: Use of Cu
      filters and low-dose settings significantly reduced radiation dose from that of
      standard settings. This phantom study process successfully guided the clinical
      implementation of low-dose studies for all ages at our institution.

PMID- 21079944
TI  - Neuroblastoma with primary pleural involvement: an unusual presentation.
AB  - Neuroblastomas are the most common neoplasms in infants. We report a 10-month-old
      who was diagnosed with thoracic neuroblastoma, with imaging showing unusual
      primary extension into the pleura, which might have an adverse staging and
      prognostic significance.

PMID- 21079945
TI  - Posterior reversible encephalopathy syndrome.

PMID- 21079946
TI  - Ion fluxes, transmembrane potential, and osmotic stabilization: a new dynamic
      electrophysiological model for eukaryotic cells.
AB  - Survival of mammalian cells is achieved by tight control of cell volume, while
      transmembrane potential has been known to control many cellular functions since
      the seminal work of Hodgkin and Huxley. Regulation of cell volume and
      transmembrane potential have a wide range of implications in physiology, from
      neurological and cardiac disorders to cancer and muscle fatigue. Therefore,
      understanding the relationship between transmembrane potential, ion fluxes, and
      cell volume regulation has become of great interest. In this paper we derive a
      system of differential equations that links transmembrane potential, ionic
      concentrations, and cell volume. In particular, we describe the dynamics of the
      cell within a few seconds after an osmotic stress, which cannot be done by the
      previous models in which either cell volume was constant or osmotic regulation
      instantaneous. This new model demonstrates that both membrane potential and cell
      volume stabilization occur within tens of seconds of changes in extracellular
      osmotic pressure. When the extracellular osmotic pressure is constant, the cell
      volume varies as a function of transmembrane potential and ion fluxes, thus
      providing an implicit link between transmembrane potential and cell volume.
      Experimental data provide results that corroborate the numerical simulations of
      the model in terms of time-related changes in cell volume and dynamics of the
      phenomena. This paper can be seen as a generalization of previous
      electrophysiological results, since under restrictive conditions they can be
      derived from our model.

PMID- 21079947
TI  - Redox regulation of morphology, cell stiffness, and lectin-induced aggregation of
      human platelets.
AB  - Redox regulation and carbohydrate recognition are potent molecular mechanisms
      which can contribute to platelet aggregation in response to various stimuli. The
      purpose of this study is to investigate the relationship between these mechanisms
      and to examine whether cell surface glycocalyx and cell stiffness of human
      platelets are sensitive to the redox potential formed by glutathione. To this
      end, human platelets were treated with different concentrations (0.05 MUM to 6
      mM) and ratios of reduced or oxidized glutathione (GSH or GSSG), and platelet
      morphological, mechanical, and functional properties were determined using
      conventional light microscopy, atomic force microscopy, and lectin-induced cell
      aggregation analysis. It was found that lowering the glutathione redox potential
      changed platelet morphology and increased platelet stiffness as well as modulated
      nonuniformly platelet aggregation in response to plant lectins with different
      carbohydrate-binding specificity including wheat germ agglutinin, Sambucus nigra
      agglutinin, and Canavalia ensiformis agglutinin. Extracellular redox potential
      and redox buffering capacity of the GSSG/2GSH couple were shown to control the
      availability of specific lectin-binding glycoligands on the cell surface, while
      the intracellular glutathione redox state affected the general functional ability
      of platelets to be aggregated independently of the type of lectins. Our data
      provide the first experimental evidence that glutathione as a redox molecule can
      affect the mechanical stiffness of human platelets and induce changes of the cell
      surface glycocalyx, which may represent a new mechanism of redox regulation of
      intercellular contacts.

PMID- 21079948
TI  - HLArestrictor--a tool for patient-specific predictions of HLA restriction
      elements and optimal epitopes within peptides.
AB  - Traditionally, T cell epitope discovery requires considerable amounts of tedious,
      slow, and costly experimental work. During the last decade, prediction tools have
      emerged as essential tools allowing researchers to select a manageable list of
      epitope candidates to test from a larger peptide, protein, or even proteome.
      However, no current tools address the complexity caused by the highly polymorphic
      nature of the restricting HLA molecules, which effectively individualizes T cell
      responses. To fill this gap, we here present an easy-to-use prediction tool named
      HLArestrictor ( http://www.cbs.dtu.dk/services/HLArestrictor ), which is based on
      the highly versatile and accurate NetMHCpan predictor, which here has been
      optimized for the identification of both the MHC restriction element and the
      corresponding minimal epitope of a T cell response in a given individual. As
      input, it requires high-resolution (i.e., 4-digit) HLA typing of the individual.
      HLArestrictor then predicts all 8-11mer peptide binders within one or more larger
      peptides and provides an overview of the predicted HLA restrictions and minimal
      epitopes. The method was tested on a large dataset of HIV IFNgamma ELIspot
      peptide responses and was shown to identify HLA restrictions and minimal epitopes
      for about 90% of the positive peptide/patient pairs while rejecting more than 95%
      of the negative peptide-HLA pairs. Furthermore, for 18 peptide/HLA tetramer
      validated responses, HLArestrictor in all cases predicted both the HLA
      restriction element and minimal epitope. Thus, HLArestrictor should be a valuable
      tool in any T cell epitope discovery process aimed at identifying new epitopes
      from infectious diseases and other disease models.

PMID- 21079949
TI  - The -159C/T polymorphism in the CD14 gene and the risk of asthma: a meta
      analysis.
AB  - The -159C/T polymorphism in the CD14 gene has been implicated in susceptibility
      to asthma, but a large number of studies have reported inconclusive results. The
      aim of this study is to investigate the association between the -159C/T
      polymorphism in the CD14 gene and the risk of asthma by meta-analysis. We
      searched Pubmed, Embase, CNKI database, Wanfang database, Weipu database, and
      Chinese Biomedical database, covering all publications (last search been
      performed on April 20, 2010). Statistical analysis was performed by using the
      softwares Revman 4.2 and STATA 10.0. A total of 17 case-control studies in 17
      articles (4,246 cases and 3,631 controls) were included in this meta-analysis.
      There was no association between this polymorphism and asthma risk in combined
      analyses (odds ratio (OR) = 0.86 and 95% confidence interval (95% CI) = 0.72
      1.02, P = 0.09 for TC + TT vs. CC). In the subgroup analysis by age, ethnicity,
      and atopic status, no significant associations of asthma risks were obtained from
      age groups, ethnic groups, and atopic groups for TC + TT vs. CC comparison. For
      atopic population, significant decreased atopic asthma risks were found among
      Asian population (OR = 0.69, 95% CI 0.52-0.92, P = 0.01) and children population
      (OR = 0.69, 95% CI 0.54-0.89, P = 0.0004) for TC + TT vs. CC comparison. This
      meta-analysis suggests that CD14 is a candidate gene for atopic asthma
      susceptibility. The -159C/T polymorphism may be a protective factor for atopic
      asthma in Asian and children. More studies are needed to validate these
      associations.

PMID- 21079950
TI  - Bone metabolic activity in hyperostosis cranialis interna measured with 18F
      fluoride PET.
AB  - PURPOSE: (18)F-Fluoride PET/CT is a relatively undervalued diagnostic test to
      measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is
      a (hereditary) bone disease characterised by endosteal hyperostosis and
      osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment
      and dysfunction of several cranial nerves. The aim of this study is to compare
      standardised uptake values (SUVs) at different sites in order to quantify bone
      metabolism in the affected anatomical regions in HCI patients. METHODS: Nine
      affected family members, seven non-affected family members and nine non-HCI non
      family members underwent (18)F-fluoride PET/CT scans. SUVs were systematically
      measured in the different regions of interest: frontal bone, sphenoid bone,
      petrous bone and clivus. Moreover, the average (18)F-fluoride uptake in the
      entire skull was measured by assessing the uptake in axial slides. Visual
      assessment of the PET scans of affected individuals was performed to discover the
      process of disturbed bone metabolism in HCI. RESULTS: (18)F-Fluoride uptake is
      statistically significantly higher in the sphenoid bone and clivus regions of
      affected family members. Visual assessment of the scans of HCI patients is
      relevant in detecting disease severity and the pattern of disturbed bone
      metabolism throughout life. CONCLUSION: (18)F-Fluoride PET/CT is useful in
      quantifying the metabolic activity in HCI and provides information about the
      process of disturbed bone metabolism in this specific disorder. Limitations are a
      narrow window between normal and pathological activity and the influence of age.
      This study emphasises that (18)F-fluoride PET/CT may also be a promising
      diagnostic tool for other metabolic bone disorders, even those with an indolent
      course.

PMID- 21079951
TI  - Hepatic epithelioid hemangioendothelioma: MR imaging findings.
AB  - We report the MRI findings in three patients with pathologically proven hepatic
      epithelioid hemangioendothelioma, a rare tumor of the liver that is not well
      described in the MR imaging literature. The recognition of the imaging features
      of this rare malignancy may help further early detection and surgical treatment
      of this potentially curable disease.

PMID- 21079952
TI  - Excellent results with cementless total hip arthroplasty and alumina-on-alumina
      pairing: minimum ten-year follow-up.
AB  - Ceramic-on-ceramic coupling is thought to be a durable alternative to metal- or
      alumina-on-polyethylene pairing. No evidence exists suggesting superior clinical
      and radiological results for hydroxyapatite-coated stems versus uncoated stems.
      The aim of this study is to report the performance of an alumina-on-alumina
      bearing cementless total hip arthroplasty and to compare stems with a tapered
      design with and without hydroxyapatite coating. We prospectively analysed the
      results of cementless tapered femoral stems (40 hydroxyapatite-coated versus 22
      uncoated stems), a metal-backed fibre mesh hydroxyapatite-coated socket and
      alumina-on-alumina pairing. Of 75 hips studied, 62 were available for follow-up
      (mean of 10.5 years after surgery). The average Harris hip score was 90. Only one
      hydroxyapatite-coated stem was revised for aseptic loosening. One instance of non
      progressive osteolysis was detected around a screw of a cup. All other components
      showed radiographic signs of stable ingrowth. Hydroxyapatite coating of the stem
      had no significant impact on the clinical or radiological results. Total hip
      arthroplasty with the presented implant and pairing provides a durable standard
      for all patients requiring hip joint replacement against which all newer
      generations of cementless implants should be judged.

PMID- 21079953
TI  - Clinical and biochemical prediction of early fatal outcome following hip fracture
      in the elderly.
AB  - Hip fracture, a moderate musculoskeletal trauma, is associated with a high
      postoperative mortality. Most patients are elderly, with comorbid conditions and
      often with heart disease. The objective of this study was to find out if clinical
      parameters and analyses of specific muscle enzymes could predict three month
      postoperative mortality. A total of 302 patients above 75 years of age with hip
      fracture were consecutively enrolled. Baseline information on age, sex and
      comorbidity assessed with the American Society of Anesthesiologists (ASA) score
      was obtained before surgery. Creatine kinase (CK), myocardium-specific creatine
      kinase (CK-MB) and troponin T (TnT) were analysed from venous blood, collected
      the day before surgery (-1) and postoperatively, within 24 hours (0) and on days
      one (+1) and four (+4). The overall three month mortality was 19.5%. Multivariate
      analyses showed that age, male sex and comorbidity (ASA) correlated with
      mortality (p = 0.027, p = 0.002, p < 0.001, respectively). Surgery induced a two-
      to threefold increase of CK and CK-MB but without any correlation with mortality.
      However, high TnT levels >0.04 MUg/l correlated significantly with death (days 
      1, +1 and +4, p = 0.003, p = 0.005 and p = 0.003, respectively). Multivariate
      analyses, adjusted for age, sex and ASA category, confirmed this correlation (day
      +4, p = 0.008). Thus, in elderly patients with comorbidities undergoing hip
      fracture surgery information on sex, age, ASA category and postoperative
      laboratory analyses on TnT provide the clinicians with useful information on
      patients at risk of fatal outcome.

PMID- 21079954
TI  - Indications and results of hip resurfacing.
AB  - The best indication for hip resurfacing is a young active patient with severe hip
      arthritis, good hip morphology and reasonable bone quality. With revision of
      either component for any reason as the endpoint, there were 68 revisions in our
      series of 3,095 consecutive Birmingham Hip Resurfacings (BHR) (1997-2009),
      including all diagnoses in all ages. This equates to a revision rate of 2.2% and
      survivorships of 99, 97 and 96% at five, ten and 13 years, respectively. In
      patients under 55 years with osteoarthritis, the survivorship is 99 and 98% at
      ten and 13 years. These results provide medium-term evidence that BHR when
      performed well in properly selected patients offers excellent outcomes and
      implant survivorship. Small changes to implant materials and design can affect
      joint function and survivorship significantly as seen from the withdrawal of
      certain resurfacing devices recently from clinical use. The clinical history of
      one device cannot be extrapolated to other devices.

PMID- 21079955
TI  - Phase 2 cross-over multicenter trial on the efficacy and safety of topical
      cyanoacrylates compared with topical silicone gel in the prevention of pathologic
      scars.
AB  - BACKGROUND: Many clinical studies on scar therapy are reported in the literature,
      but only silicone gel sheeting and corticosteroid injections are supported by
      accurate prospective controlled studies. This prospective multicenter cross-over
      phase 2 study tested the effectiveness of a topical cyanoacrylate compared with
      silicone gel in improving postsurgical scars METHODS: Patients presenting with
      symmetric breast scars after augmentation or reduction mammaplasty were enrolled
      in the study. From the same day as stitch removal, the cyanoacrylate was applied
      on one side every 3 to 5 days and the silicone gel on the other side twice a day
      for 3 months. Assessments of patients and external observers using a visual
      analog scale were recorded at scheduled visits during 1 year, and scars were
      photographed. Objective evaluations included measurements of scar width, length,
      and elevation. The statistical significance of objective parameter modifications
      was analyzed using the Wilcoxon test RESULTS: Positive effects of both tested
      products were observed during the scar maturation process, and final scars of
      good quality were achieved without any major adverse effect. The topical
      cyanoacrylate proved to be more efficacious in preventing scar widening, and this
      result was statistically significant CONCLUSIONS: The tested topical
      cyanoacrylate had a positive effect on the scar maturation process at least
      comparable with that of topical silicone gel.

PMID- 21079956
TI  - Abundance of jackfruit (Artocarpus heterophyllus) affects group characteristics
      and use of space by golden-headed lion tamarins (Leontopithecus chrysomelas) in
      Cabruca agroforest.
AB  - Cabruca is an agroforest of cacao trees shaded by native forest trees. It is the
      predominant vegetation type throughout eastern part of the range of the golden
      headed lion tamarins, Leontopithecus chrysomelas, an endangered primate endemic
      to Atlantic Forest. Understanding how lion tamarins use this agroforest is a
      conservation priority. To address this question, we documented the diet, home
      range size, group sizes and composition, density, number of litters and body
      condition of lion tamarins living in cabruca, and other habitats. Jackfruit,
      Artocarpus heterophyllus, was the most used species used by lion tamarins in
      cabruca and was widely available and used throughout the year. In cabruca, home
      range size was the smallest (22-28 ha) and density of lion tamarins was the
      highest (1.7 ind/ha) reported for the species. Group size averaged 7.4
      individuals and was not significantly different among the vegetation types. In
      cabruca, groups produced one or two litters a year, and all litters were twins.
      Adult males in cabruca were significantly heavier than males in primary forest.
      Our study is the first to demonstrate that breeding groups of golden-headed lion
      tamarins can survive and reproduce entirely within cabruca agroforest. Jackfruit
      proved to be a keystone resource for lion tamarins in cabruca, and bromeliads
      were important as an animal prey foraging microhabitat. In cases where cabruca
      contains concentrated resources, such as jackfruit and bromeliads, lion tamarins
      may not only survive and reproduce but may fare better than in other forest
      types, at least for body condition and reproduction.

PMID- 21079957
TI  - Comparison of agroforests and protected forests in the East Usambara mountains,
      Tanzania.
AB  - Comparative studies on plant species richness, endemism, floristic composition,
      and structure between protected and unprotected forests are few in the Eastern
      Arc Mountains, one of the most biodiverse ecosystems in Africa. This study from
      one mountain range, the East Usambaras, examines floristic and structural tree
      data from 41-0.5 ha plots in four types of Eastern Arc forest: active
      agroforests, recently abandoned agroforests, mature secondary forest, and natural
      forest. Active agroforests had significantly lower tree species richness, endemic
      species richness, and stand density compared to natural and mature secondary
      forest. Recently abandoned agroforests contained a higher tree species richness,
      density, and tree height than active agroforests. Active and abandoned
      agroforests were dominated by an invasive tree, Maesopsis eminii. This tree
      species makes up a large percentage of the stems in active agroforests (26%),
      recently abandoned agroforests (32%), and in the canopy of mature secondary
      forests ~ 30 years post logging (30%). Through time the increasing dominance of
      this non-native tree in active agroforests is a concern when considering the role
      of agroforests in a landscape scale conservation strategy.

PMID- 21079958
TI  - A phase I study of bevacizumab (B) in combination with everolimus (E) and
      erlotinib (E) in advanced cancer (BEE).
AB  - PURPOSE: VEGF, mTOR, and EGFR inhibitors have demonstrated anti-tumor and anti
      angiogenic effects alone and in combination with each other. This study evaluated
      the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus, and
      erlotinib combination. METHODS: Doublet therapy consisted of bevacizumab at 10
      mg/kg every 14 days and everolimus 5 mg daily which escalated to 10 mg daily.
      Erlotinib 75 mg daily was added to the phase II dose recommended phase II dose
      (RPTD) of bevacizumab and everolimus. Dose-limiting toxicity (DLT) was assessed
      in cycle 1. RESULTS: Forty-eight patients with advanced solid malignancies were
      evaluable for DLT and efficacy. No DLTs were observed in the doublet dose
      escalation. Two DLTs (grade 3 mucositis and grade 3 rash) were observed with the
      addition of erlotinib 75 mg daily. Consequently, triplet doses were adjusted and
      were better tolerated. Four patients had a partial response. Median progression
      free survival (PFS) for the doublet therapy was 6.0 months (0.5 to 32+ months)
      and 5.5 months (0.8 to 27+ months) for the triplet therapy. Systemic exposure of
      everolimus was significantly higher in combination with erlotinib (476 +/- 161 ng
      h/mL) compared to when given alone (393 +/- 156 ng h/mL; P = 0.020). CONCLUSIONS:
      The RPTD for the doublet therapy is bevacizumab 10 mg/kg every 14 days and
      everolimus 10 mg daily, and the RPTD for the triplet therapy is bevacizumab 5
      mg/kg every 14 days, everolimus 5 mg and erlotinib 75 mg daily. Prolonged disease
      stability was demonstrated in tumors known to respond to mTOR inhibition and
      potentially resistant to VEGF blockade.

PMID- 21079959
TI  - Phase I study of LY2181308, an antisense oligonucleotide against survivin, in
      patients with advanced solid tumors.
AB  - PURPOSE: LY2181308 is an antisense oligonucleotide that complementarily binds to
      survivin mRNA and inhibits its expression in tumor tissue. This phase I dose
      escalation study evaluated the tolerability, pharmacokinetics, and anticancer
      activity of LY2181308 in Japanese. METHODS: Patients with solid tumors refractory
      to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous
      infusion for 3 consecutive days and thereafter once a week. RESULTS: LY2181308
      was administered to 14 patients, aged 44-73 (median 60) years. Flu-like syndrome,
      prolonged prothrombin time-international normalized ratio (PT-INR),
      thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The
      dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/gamma-GTP in 1
      patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long
      terminal half-life of 21 days and an extensive tissue distribution of LY2181308.
      In 12 evaluable patients, one patient had stable disease, while the remaining 11
      patients had progressive disease. CONCLUSIONS: LY2181308 monotherapy is well
      tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile
      warrants further evaluation of LY2181308 in combination with cytotoxic agents or
      radiotherapy.

PMID- 21079960
TI  - The therapeutic efficacy of S-1 against orthotopically implanted human pleural
      mesothelioma cells in severe combined immunodeficient mice.
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1
      has been developed as a novel oral antineoplastic agent based on the modulation
      of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate the
      preclinical therapeutic effect of S-1 on MPM. METHODS: We used three human MPM
      cell lines, Y-MESO-14, NCI-H290 and MSTO-211H. In vitro proliferation of human
      MPM cells was determined by MTT assay. Human MPM cells were orthotopically
      implanted into thoracic cavity of SCID mice. Tumor-bearing mice were treated with
      S-1 or vehicle. RESULTS: The combination of 5-FU and 5-chloro-2,4
      dihydroxypyridine (CDHP) was more effective than 5-FU alone in inhibiting MPM
      cell proliferation in vitro. This combination was most effective in Y-MESO-14
      cells, which co-expressed high protein level of dihydropyrimidine dehydrogenase
      (DPD) and thymidine phosphorylase (TP). In vivo data showed that treatment with S
      1 significantly reduced thoracic tumors and pleural effusion produced by Y-MESO
      14 cells. Moreover, treatment with S-1 prolonged the survival of Y-MESO-14 cell
      bearing SCID mice. CONCLUSIONS: We demonstrated that S-1 was effective for
      inhibiting the proliferation of MPM cells, particularly with both DPD and TP
      expressions, suggesting that S-1 might be therapeutically effective for control
      of MPM.

PMID- 21079961
TI  - Extremely high frequency electromagnetic irradiation in combination with
      antibiotics enhances antibacterial effects on Escherichia coli.
AB  - Antibacterial effects of the electromagnetic irradiation (EMI) of 51.8 and 53 GHz
      frequencies with low intensity (the flux capacity of 0.06 mW/cm(2)) and non
      thermal action were investigated upon direct irradiation of E. coli K12.
      Significant decrease in bacterial growth rate and in the number of viable cells,
      marked change in H(+) and K(+) transport across membrane were shown. Subsequent
      addition of kanamycin or ceftriaxone (15 or 0.4 MUM, respectively) enhanced the
      effects of irradiation. This was maximally achieved at the frequency of 53 GHz.
      These all might reveal membrane as probable target for antibacterial effects.
      Apparently, the action of EMI on bacteria might lead to changed membrane
      properties and to antibiotic resistance. The results should improve using
      extremely high frequency EMI in combination with antibiotics in biotechnology,
      therapeutic practice, and food industry.

PMID- 21079962
TI  - The role of cell wall revealed by the visualization of Saccharomyces cerevisiae
      transformation.
AB  - Transformation is an indispensable method for the manipulation of Saccharomyces
      cerevisiae cell. The spf1 cell, in which the gene encoding an endoplasmic
      reticulum-located P-type ATPase is deleted, has been known to show the high
      transformation phenotype. In this study, fluorescent microscopic observation of
      transformation process of S. cerevisiae using plasmid DNA labelled with
      fluorescent DNA probe, YOYO-1, suggested that the spf1 cell absorbed more plasmid
      DNA on cellular surface than did the wild-type cell and the unwashed cell did
      more plasmid DNA than the washed cell. The amounts of the absorbed DNA correlated
      with the transformation efficiency (number of transformants per MUg plasmid DNA)
      and frequency (transformation efficiency per viable cell number). The high
      transformation phenotype of spf1 cell and the effect of heat shock, which
      effectively induces the transformation of intact cell, disappeared upon cell wall
      digestion. Electron microscopic observation of the transformation process using
      negatively charged Nanogold as a mimic of plasmid DNA supported the result
      obtained using YOYO-1 and implied that plasmid DNA enters into cell together with
      membrane structure. These data strongly suggest that during the transformation of
      intact cell, plasmid DNA is initially absorbed on the cell wall, passes through
      the cell wall with the aid of heat shock, reaches to the membrane, and enters
      into the cell together with the membrane structure and that the capacity of the
      cell wall to absorb DNA is at least one of the determinants of transformation
      efficiency and frequency.

PMID- 21079963
TI  - Phenotypic and genotypic characterization Vibrio cholerae O139 of clinical and
      aquatic isolates in China.
AB  - To enhance the understanding of epidemiological impact of environmental Vibrio
      cholerae O139 strains, we characterized 10 clinical and 20 environmental isolates
      collected from human clinical samples and Pear River estuary during 2006 to 2008.
      Isolates were tested by PCR for eight virulence genes: cholera toxin (ctxA),
      zonula occludens toxin (zot), accessory cholera enterotoxin (ace), hemolysin
      (hlyA), NAG-specific heat-stable toxin (st), toxin-coregulated pilus (tcpA),
      outer membrane protein (ompU), and regulatory protein genes (tcpI). Genetic
      relatedness was assessed by pulsed-field gel electrophoresis (PFGE), and
      antibiotic susceptibility was determined using disk diffusion. Seven of eight
      virulence markers were detected in six clinical isolates and one environmental
      isolate. One clinical and one environmental isolate were positive for six
      virulence markers. 60% clinical isolates showed multi-drug resistance to
      tetracycline (TET), Nalidixic acid (NAL), chloramphenicol (CHL), and ampicillin
      (AMP), 70% were resistant to Trimethoprim + Sulfamethoxazole (SXT), while only
      35% environmental strains were resistant to SXT. PFGE analysis revealed that the
      isolates in this study were formed three clusters. Cluster III was more related
      to strains from diarrheal patients than the strains in other clusters. Different
      from the clinical strains, most environmental strains lacked CTX and TCP gene
      clusters. Most environmental strains possess a single resistance profile, while
      most clinical isolates show multidrug resistant. PFGE analysis indicated the
      cluster III has more possibility to become a potential pathogenic clonal cluster.

PMID- 21079964
TI  - [Are sarcoma centers needed in Germany? Experience gained with the Bonner GIST
      register].
AB  - Due to their rarity and multiple subtypes, there is scant experience with
      sarcomas. Any effective targeted therapy depends on precise diagnosis of the
      tumor group using molecular markers and, increasingly, mutation testing. The
      necessary histopathological expertise and molecular diagnostic tools are usually
      only found at specialized centers. Using the Bonner GIST register as an example,
      the advantages of this kind of register from a diagnostic and therapeutic
      perspective will be discussed. Material submitted for gastrointestinal stromal
      tumors and other mesenchymal tumors, as well as the supervision of pathological
      referencing for national and international studies have made accurate diagnosis
      and appropriate therapy strategies ever more possible. The introduction of
      epidemiological as well as interdisciplinary sarcoma registers is a prerequisite
      for the improvement of sarcoma diagnostics and therapy.

PMID- 21079966
TI  - Generation of transgenic watermelon resistant to Zucchini yellow mosaic virus and
      Papaya ringspot virus type W.
AB  - Zucchini yellow mosaic virus (ZYMV) and Papaya ringspot virus type W (PRSV W) are
      major limiting factors for production of watermelon worldwide. For the effective
      control of these two viruses by transgenic resistance, an untranslatable chimeric
      construct containing truncated ZYMV coat protein (CP) and PRSV W CP genes was
      transferred to commercial watermelon cultivars by Agrobacterium-mediated
      transformation. Using our protocol, a total of 27 putative transgenic lines were
      obtained from three cultivars of 'Feeling' (23 lines), 'China baby' (3 lines),
      and 'Quality' (1 line). PCR and Southern blot analyses confirmed that the
      chimeric construct was incorporated into the genomic DNA of the transformants.
      Greenhouse evaluation of the selected ten transgenic lines of 'Feeling' cultivar
      revealed that two immune lines conferred complete resistance to ZYMV and PRSV W,
      from which virus accumulation were not detected by Western blotting 4 weeks after
      inoculation. The transgenic transcript was not detected, but small interfering
      RNA (siRNA) was readily detected from the two immune lines and T(1) progeny of
      line ZW 10 before inoculation, indicating that RNA-mediated post-transcriptional
      gene silencing (PTGS) is the underlying mechanism for the double-virus
      resistance. The segregation ratio of T(1) progeny of the immune line ZW10
      indicated that the single inserted transgene is nuclearly inherited and
      associated with the phenotype of double-virus resistance as a dominant trait. The
      transgenic lines derived from the commercial watermelon cultivars have great
      potential for control of the two important viruses and can be implemented
      directly without further breeding.

PMID- 21079965
TI  - Infliximab, a TNF-alpha antagonist treatment in patients with ankylosing
      spondylitis: the impact on depression, anxiety and quality of life level.
AB  - The objective of this study was to assess the effect of infliximab on depression,
      anxiety and quality of life in patients with active ankylosing spondylitis (AS).
      In this 6-week longitudinal study, 16 patients with AS were assessed. Active
      disease as defined by BASDAI >=4.0 was sought for inclusion. Infliximab was
      administered 5 mg/kg at 0, 2 weeks and 6 weeks. Collected data included age, sex
      and date of onset of rheumatologic disease. Activity of disease was measured
      using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Biological
      activity was evaluated with erythrocyte sedimentation rate (ESR) and C-reactive
      protein (CRP). ESR and CRP were assessed at baseline and day 42. The Hospital
      Anxiety and Depression scale (HADS), Beck Depression Inventory (BDI) and 36-item
      Short Form Health Survey (SF-36) were used to evaluate anxiety, depression and
      quality of life. BASDAI, SF-36, HADS and BDE were assessed prior to the initial
      infliximab dose and at 2nd, 14th and 42nd day. Seven (43.8%) AS patients had
      depression scores above the cut off value for both the HADS depression (HADS-D)
      and BDI and 4 (25 %) had high HADS anxiety scores at baseline. Significant time
      effect for BDI and HADS-D scores were observed. Although significantly lower BDI
      scores were found after first, second and third infusions of infliximab, compared
      to initial score, the significant decrease in HADS-D appeared after second and
      third infusions. A significant time effect for HADS-anxiety scores were found as
      well. All of the subscales of SF-36 improved significantly during the course,
      with an exception of role emotional, for which the difference approached to the
      significance. The change in BASDAI scores and CRP and ESR, in the treatment
      process, were not correlated with the change in depression and anxiety scores.
      Infliximab which is an anti-TNF-alpha drug, may be effective in the treatment of
      depression accompanying AS. Possible implications for the treatment of major
      depressive disorder were discussed, as well.

PMID- 21079967
TI  - The fish-hook configuration of the distal ureter indicates bladder outlet
      obstruction due to benign prostatic hyperplasia.
AB  - PURPOSE: The aim of this retrospective study was to evaluate in a historical
      series of patients whether morphological changes of the urinary tract imaged on
      intravenous urography (IVU) are associated with clinical or urodynamic data.
      METHODS: During a 1-year period, every man 45 years or older with lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia was systematically
      evaluated with multi-channel computer-urodynamic investigation and IVU. Men with
      urinary retention, known bladder stones or diverticula, severely impaired renal
      function, or allergy to iodine contrast media were excluded. Structural
      alterations of the urinary tract were correlated with clinical and urodynamic
      data using logistic regression analysis. RESULTS: Data on 203 consecutive
      patients were available for analysis. Multivariate analysis demonstrated that the
      "fish-hook" configuration of the distal ureter (also known as "hockey-stick", or
      "J-shaped" ureter) was the only sign significantly associated with benign
      prostatic obstruction (BPO) (odds-ratio 3.64; 95% confidence interval 1.69-7.83;
      P < 0.001). The sensitivity, specificity, positive and negative predictive values
      of the "fish-hook" ureter configuration sign to detect BPO was 53, 76, 61 and
      70%, respectively. Bladder trabeculation, upper urinary tract dilatation, or
      bladder base elevation were not associated with BPO, detrusor overactivity,
      detrusor underactivity, bladder low-compliance or any clinical data. CONCLUSIONS:
      The "fish-hook" shape of the distal ureter(s) indicates BPO and may be a result
      of prostate median lobe enlargement.

PMID- 21079969
TI  - Experience on semirigid ureteroscopy and pneumatic lithotripsy in children at a
      single center.
AB  - AIM: Ureteroscopy in children with miniaturized instruments is becoming popular
      with the advent of pediatric ureteroscopes and laser lithotriptors. We had been
      performing pediatric ureteroscopies with a 7.5 Fr. semirigid ureteroscope and
      pneumatic lithotriptor, used in adults as well. Herein, we present our experience
      in pediatric ureteroscopy with a semirigid 7.5 Fr. ureteroscope and pneumatic
      lithotriptor with a specific focus on changes in success and complication rates
      with time. MATERIALS METHODS: We retrospectively reviewed the charts of all
      patients younger than 18 years old who underwent ureteroscopic intervention with
      a 7.5 Fr. semirigid ureteroscope and pneumatic lithotriptor at our institute
      between January 2000 and September 2009. Patient characteristics were recorded
      including date of surgery, age, sex, stone size and location, ureteroscopy
      technique, duration of surgery, the result of surgery, complication,
      postureteroscopy ureteral stenting, follow-up duration and final imaging.
      RESULTS: A total of 48 children (28 boys, 20 girls) with a mean age of 7.6 years
      (range: 9 months-18 years) have undergone 54 ureteroscopic intervention. Thirty
      eight (79.1%) children were <10 years of age and 17 (35.4%) were <4 years of age.
      Stone-related ureteroscopy number was 51. Mean stone diameter was 6.6 mm (4-20
      mm). Mean duration of surgery was 77 min (25-150 min). Overall success rate was
      84.3%, and overall complication rate was 14.8%. CONCLUSIONS: Ureteroscopic
      management of ureteral stones is safe and effective in children >1 year of age
      with a 7.5 Fr. semirigid ureteroscope and pneumatic lithotriptor.

PMID- 21079968
TI  - Tumor volume as a predictor of adverse pathologic features and biochemical
      recurrence (BCR) in radical prostatectomy specimens: a tale of two methods.
AB  - PURPOSE: The prognostic value of tumor volume in predicting biochemical
      recurrence after prostatectomy has been debated. Our aim in this study was to (a)
      evaluate tumor volume as an independent predictor of adverse pathologic outcomes
      and BCR and (b) determine the effect of two different methods of tumor volume
      estimation. METHODS: We reviewed the charts of 3,087 patients who underwent
      radical prostatectomy at Vanderbilt University Medical Center between 2000 and
      2008; of which 1,747 patients had data sufficient for analysis. Prostate
      specimens were processed as whole mount between 2000 and 2003 and then via
      systematic sampling from 2003 to 2008, with tumor volume measured by planimetry
      in the whole-mount group and tumor volume estimated by percent tumor involvement
      in the systematic sampling group. RESULTS: Tumor volume estimates were higher
      with SS than with WM. There were significant associations between larger tumor
      volume and adverse pathological outcomes, regardless of pathologic method (all
      with P<0.001). Controlling for other pathologic parameters, tumor volume was an
      independent predictor of PGS, EPE, and SM in logistic regression models (P<0.001
      for TV in all models). Tumor volume was demonstrated to be an independent
      predictor of BCR in the WM group (1.06, 95% CI 1.01-1.11, P=0.013), though tumor
      volume was not a significant predictor of BCR in the SS group. CONCLUSIONS:
      Though the prognostic value of tumor volume is debated, our data demonstrate that
      tumor volume, when calculated via planimetry on whole-mount pathologic
      sectioning, is a significant predictor of biochemical recurrence after
      prostatectomy.

PMID- 21079970
TI  - Quantitative magnetic resonance analysis and a morphometric predictive model
      reveal lean body mass changes in migrating Nearctic-Neotropical passerines.
AB  - Most studies of lean mass dynamics in free-living passerine birds have focused on
      Old World species at geographical barriers where they are challenged to make the
      longest non-stop flight of their migration. We examined lean mass variation in
      New World passerines in an area where the distribution of stopover habitat does
      not require flights to exceed more than a few hours and most migrants stop flying
      well before fat stores near exhaustion. We used either quantitative magnetic
      resonance (QMR) analysis or a morphometric model to measure or estimate,
      respectively, the fat and lean body mass of migrants during stopovers in New
      York, USA. With these data, we examined (1) variance in total body mass explained
      by lean body mass, (2) hourly rates of fat and lean body mass change in single
      capture birds, and (3) net changes in fat and lean mass in recaptured birds. Lean
      mass contributed to 50% of the variation in total body mass among white-throated
      sparrows Zonotrichia albicollis and hermit thrushes Catharus guttatus. Lean mass
      of refueling gray catbirds Dumetella carolinensis and white-throated sparrows,
      respectively, increased 1.123 and 0.320 g h(-1). Lean mass of ovenbirds Seiurus
      aurocapillus accounted for an estimated 33-40% of hourly gains in total body
      mass. On average 35% of the total mass gained among recaptured birds was lean
      mass. Substantial changes in passerine lean mass are not limited to times when
      birds are forced to make long, non-stop flights across barriers. Protein usage
      during migration is common across broad taxonomic groups, migration systems, and
      migration strategies.

PMID- 21079971
TI  - Economics of comb wax salvage by the red dwarf honeybee, Apis florea.
AB  - Colonies of Apis florea, which only abscond a short distance, usually return to
      salvage old nest wax; but, those colonies, and all other honeybee species which
      go considerably further, do not. Wax salvage would clearly be counter-productive
      unless the energy input/energy yield threshold was a profitable one. There are
      two possible trade-offs in this scenario, the trade-off between the energy
      expended to recover the wax (recovering hypothesis) as against that of replacing
      the wax by new secretion (replacing hypothesis). In order to compare the two
      hypotheses, the fuel costs involved in salvaging wax on one return trip, the
      average flower handling time, flight time and relative values for substituting
      the salvaged wax with nectar were calculated. Moreover, the energy value of the
      wax was determined. Net energy gains for salvaged wax were calculated. The energy
      value of the salvaged wax was 42.7 J/mg, thus too high to be the limiting factor
      since salvaging costs are only 642.76 mJ/mg (recovering hypothesis). The recovery
      costs (642.76 mJ/mg) only fall below the replacement costs for absconding
      distance below 115 m thus supporting the replacing hypothesis. This energetic
      trade-off between replacing and recycling plus the small absconding range of A.
      florea might explain why A. florea is probably the only honeybee species known to
      salvage wax and it parsimoniously explains the underlying reasons why A. florea
      only salvages wax from the old nest if the new nesting site is less than 100-200
      m away-energetically, it pays off to recycle.

PMID- 21079972
TI  - Glibenclamide increases post-fatigue tension in slow skeletal muscle fibers of
      the chicken.
AB  - In contrast to fast-twitch skeletal muscle fibers of the chicken, slow-twitch
      fibers are fatigue-resistant. In fast fibers, the fatigue process has been
      related to K(ATP) channels. In the present study, we investigated the action of
      glibenclamide (an anti-diabetic sulphonylurea that acts on K(ATP) channels) on
      fatigued slow skeletal muscle, studying twitch and tetanus tension after inducing
      the muscle to fatigue by continuous electrical stimulation. Our results showed
      that glibenclamide (150 MUM) increased post-fatigue twitch tension by about 25%
      with respect to the fatigued condition (P < 0.05). In addition, glibenclamide
      (150 MUM) increased post-fatigue tetanic tension (83.61 +/- 15.7% in peak
      tension, and 85.0 +/- 19.0% in tension-time integral, P = 0.02, and 0.04,
      respectively; n = 3). Moreover, after exposing the muscle to a condition that
      inhibits mitochondrial ATP formation in order to activate K(ATP) channels with
      cyanide (10 mM), tension also diminished, but in the presence of glibenclamide
      the effect produced by cyanide was abolished. To determine a possible increase in
      intracellular calcium concentration, the effects of glibenclamide on caffeine
      evoked contractures were explored. After muscle pre-incubation with glibenclamide
      (150 MUM), tension of caffeine-evoked contractures increased (6.5 +/- 1.5% in
      maximal tension, and 5.9 +/- 3.8% in tension-time integral, P < 0.05). These
      results suggest a possible role of K(ATP) channels in the fatigue process, since
      glibenclamide increases twitch and tetanus tension in fatigued slow muscle of the
      chicken and during metabolic inhibition, possibly by increasing intracellular
      calcium.

PMID- 21079973
TI  - Expression of phosphorylated Stat5 predicts expression of cyclin D1 and
      correlates with poor prognosis of colonic adenocarcinoma.
AB  - PURPOSE: Constitutive activation of signal transducer and activator of
      transcription-5 (Stat5) was recently found to be associated with tumor
      progression through stimulating cell proliferation and preventing apoptosis.
      However, it is not clear how activated Stat5 is expressed in colon cancer. We
      aimed to investigate the correlation between phosphorylated Stat5 (p-Stat5)
      expression and cell cycle regulators (cyclin D1) expression in colonic
      adenocarcinoma and the relationship between expression of these two proteins and
      various clinicopathological parameters, including overall survival. METHODS: P
      Stat5 and cyclin D1 expression were determined by immunohistochemical staining
      from 169 cases of resected colonic adenocarcinoma specimens. RESULTS: P-Stat5
      expression correlated with cyclin D1 expression (r = 0.250, P = 0.001). P-Stat5
      positive staining was associated with the depth of tumor invasion (P = 0.002).
      Univariate survival analysis showed that lymph node metastasis, distant
      metastasis, TNM stage (all P < 0.0001), T stage (P = 0.024), p-Stat5-positive
      expression (P = 0.002), and cyclin D1-positive expression (P = 0.039) were
      associated with shorter survival in patients with colonic adenocarcinoma.
      Multivariate survival analysis showed that only distant metastasis (P < 0.001;
      hazard ratio [HR] = 4.96), TNM stage (P < 0.001; HR = 9.80), and p-Stat5
      overexpression (P = 0.020; HR = 1.84) were independent predictors of poor
      prognosis. CONCLUSIONS: Our findings provide the first evidence that p-Stat5 may
      play an important role in cyclin D1 overexpression and contribute to colonic
      adenocarcinoma progression.

PMID- 21079974
TI  - Surgical repair of rectovaginal fistulas--a challenge.

PMID- 21079976
TI  - Depigmenting mechanism of NSAIDs on B16F1 melanoma cells.
AB  - The aim of the present work was to clarify the anti-melanogenic mechanism of non
      steroidal anti-inflammatory drugs (NSAIDs). Mefenamic acid, diclofenac, and
      nimesulide were used in this study, and these drugs inhibit melanin synthesis in
      B16F1 melanoma cells. To elucidate the anti-melanogenic mechanism of NSAIDs, we
      performed western blotting analysis for melanogenic proteins, such as tyrosinase,
      TRP-1, and TRP-2. All NSAIDs used in this study inhibited tyrosinase protein
      level. Semi-quantitative RT-PCR analysis showed that the depigmentation effect of
      mefenamic acid and nimesulide might be due to the inhibition of tyrosinase gene
      transcription. These results indicate that NSAIDs inhibit alpha-MSH-enhanced
      melanin synthesis, and are candidate anti-melanogenic agents since they might be
      effective in hyperpigmentation disorders.

PMID- 21079975
TI  - Transepithelial heme-iron transport: effect of heme oxygenase overexpression.
AB  - BACKGROUND: Heme iron is found in the diet mainly in the form of hemoglobin and
      myoglobin. It is known that heme iron (heme-Fe) and inorganic iron are absorbed
      differently. Intracellularly, heme oxygenase-1 (HO1) participates in the cleavage
      of the heme ring producing biliverdin, CO and ferrous iron. Iron released from
      heme becomes part of labile iron pool, and it can be stored in ferritin or
      released through the basolateral membrane. The mechanism by which heme-Fe is
      metabolized within cells is not completely understood. OBJECTIVE: This study
      focused on the uptake and transport of heme iron and on the role of heme
      oxygenase-1 on heme iron metabolism. DESIGN: Caco-2 cells were incubated with
      different concentrations of heme-Fe. A full-length heme oxygenase-1 cDNA was
      expressed in Caco-2 cells and intracellular iron and heme-Fe content, heme
      uptake, heme and iron transport and heme oxygenase-1 immunolocalization were
      assessed in these cells. RESULTS: Heme-Fe was bioavailable and induced an
      intracellular increase in iron, ferritin and HO1 levels and a decrease in DMT1
      expression. In cells overexpressing HO1, heme-Fe uptake and transepithelial Fe
      transport was higher than in controls. Most heme-Fe was metabolized to free iron,
      most of which was found mainly in the basolateral chamber. However, there is a
      fraction of heme that is delivered intact to the basolateral side. In a high heme
      Fe condition, HO1 is found near the plasma membrane. CONCLUSIONS: These results
      suggest that heme oxygenase-1 catabolizes most of the heme-Fe and favors iron
      influx and efflux in intestinal cells.

PMID- 21079978
TI  - Prospective evaluation of combined local bupivacaine and steroid injections for
      the management of chronic vaginal and perineal pain.
AB  - PURPOSE: Vaginal/perineal pain is common following obstetric trauma or vaginal
      surgery for prolapse and may have a serious impact on sexual function and quality
      of life. Local injections of corticosteroids, local anaesthetic and hyaluronidase
      are treatment options for chronic pain; however, there are no published studies
      to support their efficacy. The objective of this study was to evaluate
      prospectively the efficacy of perineal/vaginal injections for chronic localised
      pain following childbirth or vaginal surgery. METHODS: Consecutive women with
      chronic vaginal/perineal pain were recruited in this prospective series (audit).
      Pain severity and sexual function were determined using a visual analogue scale
      (VAS 0-10) and the abbreviated sexual function questionnaire (ASFQ) respectively.
      Patients underwent local injections with a combination of 0.5% bupivacaine (10
      ml), hydrocortisone (100 mg) and hyaluronidase (1,500 IU). Follow-up was
      undertaken at four-weekly intervals. Further injections were performed as
      clinically indicated. RESULTS: Fifty-three women underwent >=1 injections [mean:
      1.86 (range: 1-4)]. Mean interval from index childbirth [43/53 (81%)] or surgical
      intervention [10/53 (19%)] was 8 months (range 12 weeks-20 years). Twenty-seven
      women (51%) were sexually active. All reported dyspareunia. Fifteen (28%) women
      required 1 and 31(59%) two injections. Pre treatment VAS pain scores were 6.1
      versus 4.1 after first injection (p = 0.0002, 95% CI 1.01-3.05) and mean ASFQ
      scores increased from 18.1 to 29.1 (p = 0.01, 95% CI -17.2 to -2.3) 4 weeks post
      injection. There were no adverse events or morbidity. 24/27 (89%) sexually active
      women with dyspareunia resolved and 18/26 (69%) sexually inactive women resumed
      satisfactory sexual activity 8 weeks post-injection. CONCLUSION: In our series,
      this treatment was well tolerated and significant improvements in pain scores and
      sexual function were observed.

PMID- 21079979
TI  - Seasonality of spina bifida in Northern Germany.
AB  - PURPOSE: To verify a seasonal variation in the incidence of spina bifida and thus
      to identify possible environmental triggers leading to its developement. METHODS:
      An interdisciplinary approach has been taken to develop a better understanding of
      spina bifida through collaborative efforts from investigators specializing in
      genetics, fetal pathology, paediatrics, neuro-surgery and prenatal
      ultrasonographic diagnosis. All pregnancies with fetal spina bifida were
      retrospectively analyzed from May 1 1993 through May 1 2010 at Luebeck University
      Fetal Health Center. Results were used to construct a model to predict the
      occurrence of fetal spina bifida based on seasonal variation and environmental
      influence reflected by climatic changes and environmental pollution. Furthermore,
      data were categorized in respect to the date of conception and subdivided into
      date of conception during summer (April-September) and winter months (October
      March). RESULTS: Neither a seasonal distribution of conception for fetuses with
      spina bifida in the defined time frame could be verified nor a relevant influence
      of the analyzed environmental factors on the prevalence of spina bifida could be
      proved. The incidence of spina bifida has remained relatively stable within the
      last 17 years at 2.5 per 1,000 screened pregnancies. CONCLUSION: Since we were
      unable to demonstrate a relationship between seasonal variation and certain
      environmental factors on the incidence of fetal spina bifida, other factors
      should be investigated for a possible association with the onset of fetal spina
      bifida.

PMID- 21079980
TI  - Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum.
AB  - PURPOSE: To evaluate the role of Helicobacter pylori (H. pylori) in the
      pathogenesis of hyperemesis gravidarum (HG) and the value of adding a non
      teratogenic regimen for its treatment in intractable cases. METHODS: Eighty
      hyperemesis gravidarum cases were recruited from Ain Shams University out patient
      clinics. A complete history was taken including history of medical disorders and
      chronic medications intake as non steroidal anti-inflammatory drugs. After
      general and local examination, ultrasound was done for all cases to exclude
      obstetric causes of hyperemesis. Eighty normal pregnant women acted as control.
      Serum test for H. pylori IgG antibody titre was done for all patients and
      controls. RESULTS: Seventy-one cases among the 80 HG cases and twenty-four out of
      the 80 controls were H. pylori positive. Eight HG cases developed severe
      intractable vomiting. Three of them developed attacks of hematemesis. Gastroscopy
      done for the eight cases revealed antral gastritis and duodenitis. Gastric and
      duodenal erosions were found in two cases. The eight patients received a non
      teratogenic regimen for treatment. Attacks of vomiting decreased and pregnancy
      continued till delivery of healthy newborns. CONCLUSION: Screening for H. pylori
      should be added to the investigations of hyperemesis gravidarum cases. Non
      teratogenic treatment can be considered in intractable cases.

PMID- 21079981
TI  - Prevalence rate of group B streptococcal colonization among women in labor at
      King Abdul-Aziz University Hospital.
AB  - OBJECTIVE: This study aims to determine the prevalence of group B streptococcus
      (GBS) colonization in laboring women. SETTING: Delivery room at King Abdul-Aziz
      University Hospital (KAUH), Jeddah, Saudi Arabia. STUDY DESIGN: Prospective.
      METHODS: Rectal and vaginal swabs were taken from low-risk women at two occasions
      the first around 33.5 +/- 1.6 weeks gestational age and the second when they
      present in labor. RESULTS: 326 parturient women were examined during the study
      period. The overall intrapartum prevalence maternal GBS colonization rate was
      31.6% at the mean gestational age 39.2 +/- 2.5. CONCLUSION: The prevalence of
      intrapartum GBS colonization increase as women approach term.

PMID- 21079982
TI  - Transvaginal ultrasound of cervical length and its correlation to digital
      cervical examination, time to spontaneous labor and mode of delivery.
AB  - PURPOSE: The objective of this study was to determine if transvaginal ultrasound
      (TVUS) examination of cervical length correlates to digital pelvic examination
      and if it can predict time to and mode of delivery in term pregnancies. METHODS:
      We conducted a prospective cohort study of 726 consecutive non-laboring, term
      pregnant women presenting to University-based antenatal testing unit between 1
      July 2001 and 31 March 2002. Subjects underwent a TVUS for cervical length
      followed by a digital cervical examination by a physician blinded to the results
      of the ultrasound. Linear regression analysis was used to correlate the findings
      of cervical length by ultrasound with cervical dilatation and effacement by
      digital examination. RESULTS: In 726 women, the relationship between TVUS
      cervical length and cervical dilatation and effacement measured digitally were
      found to be significantly related (p < 0.001), but weak, with a 15 and 23%
      goodness of fit, respectively, based on the linear model. Using multivariate
      logistic and linear regression, respectively, TVUS cervical length predicted mode
      of delivery but did not predict time to spontaneous labor. Digital measurement of
      cervical dilatation was predictive of time to spontaneous labor. CONCLUSIONS:
      There is a statistically significant correlation between TVUS measurement of
      cervical length and digital cervical exam though the correlation is weak. TVUS
      measurement of cervical length was predictive of mode of delivery while
      controlling for digital cervical examination, parity and time to spontaneous
      labor. Digital cervical dilatation was predictive of time to spontaneous
      delivery.

PMID- 21079983
TI  - Expression of tyrosine kinase receptor B in eutopic endometrium of women with
      adenomyosis.
AB  - OBJECTIVE: Our study is to investigate whether tyrosine kinase receptor B (TrkB)
      is expressed in eutopic endometrium of women with adenomyosis and its association
      with clinical characteristics. METHODS: We collected endometrial tissues from 31
      women with adenomyosis and 30 adenomyosis-free women undergoing surgery for
      benign indications. TrkB expression was assessed by immunohistochemistry and
      reverse-transcription polymerase chain reaction. RESULTS: Immunoreactive staining
      for TrkB was present as brown flocculent precipitate in the endometrial cells.
      The average level of TrkB protein (quantitation of immunostaining intensity) in
      secretory endometrial samples of women with adenomyosis was significantly higher
      than that in controls (p < 0.01). The average level of TrkB messenger RNA (mRNA)
      expression of women with adenomyosis was significantly higher than that of
      controls at secretory phase (p < 0.01). In addition, the immunostaining
      quantitation of TrkB protein was positively correlated with the serum CA125 (r =
      0.308, p = 0.016) and dysmenorrhea (r = 0.393, p = 0.002). CONCLUSIONS: Our study
      revealed elevation of TrkB protein and mRNA expression in the secretory
      endometrium of women with adenomyosis. Moreover, TrkB protein expression in human
      endometrium was positively correlated with the serum CA125 and dysmenorrhea. TrkB
      might contribute to the pathogenesis and progression of adenomyosis.

PMID- 21079984
TI  - Ectopic olfactory neuroblastoma: report of four cases and a review of the
      literature.
AB  - Our objective is to present a short series of four rare cases of ectopic
      olfactory neuroblastoma. Our methods present four case reports of ectopic
      olfactory neuroblastoma and a review of the literature for management and
      treatment of this disease. The results indicate short case series reports of
      ectopic olfactory neuroblastoma arising from the anterior ethmoidal sinuses, the
      nasopharynx, the lateral nasal wall and the floor of the nose. The discussion
      focuses on likely origins of ectopic olfactory neuroblastoma, its clinical
      features and management. We conclude that ectopic olfactory neuroblastoma is a
      rare disease. Treatment principles are the same for non-ectopic disease and
      guided by extension into adjacent structures such as the orbit or anterior
      cranial fossa and usually involves surgery with or without adjuvant radiotherapy.

PMID- 21079986
TI  - Lateral trunk flexion in Parkinson's disease: EMG features disclose two different
      underlying pathophysiological mechanisms.
AB  - Pisa Syndrome is clinically defined as the sustained lateral bending of the trunk
      worsened by a prolonged sitting position or by walking. Pisa syndrome, also
      termed lateral trunk flexion (LTF), has been rarely reported in patients affected
      by Parkinson's disease (PD) and, therefore, the pathophysiology has been poorly
      investigated. In some cases, the hyperactivity of paravertebral muscles
      contralateral to the leaning side has been interpreted as a sign of dystonia;
      however, it is well known that paravertebral muscles flex the trunk
      ipsilaterally. We systematically explored the pattern of muscular activation
      underlying the lateral flexion of trunk in 10 PD patients (mean disease duration:
      9.2 +/- 3.0 years) presenting LTF for 3.6 +/- 2.1 years. EMG performed during
      stance and during left and right lateral trunk flexion showed a continuous
      ipsilateral muscular hyperactivity in three patients, while in the remaining ones
      there was no ipsilateral activity during standing and a tonic contraction of
      paravertebral muscles contralateral to the leaning side. In conclusion, this EMG
      study investigating the synergies of paravertebral muscles during dynamic
      conditions detected two different patterns with a typical dystonic activation in
      only a minority of cases. Possible pathophysiologic mechanisms and treatment
      approaches are discussed.

PMID- 21079985
TI  - Nucleocytoplasmic mRNP export is an integral part of mRNP biogenesis.
AB  - Nucleocytoplasmic export and biogenesis of mRNPs are closely coupled. At the
      gene, concomitant with synthesis of the pre-mRNA, the transcription machinery,
      hnRNP proteins, processing, quality control and export machineries cooperate to
      release processed and export competent mRNPs. After diffusion through the
      interchromatin space, the mRNPs are translocated through the nuclear pore complex
      and released into the cytoplasm. At the nuclear pore complex, defined
      compositional and conformational changes are triggered, but specific
      cotranscriptionally added components are retained in the mRNP and subsequently
      influence the cytoplasmic fate of the mRNP. Processes taking place at the gene
      locus and at the nuclear pore complex are crucial for integrating export as an
      essential part of gene expression. Spatial, temporal and structural aspects of
      these events have been highlighted in analyses of the Balbiani ring genes.

PMID- 21079987
TI  - Estrogens regulate the expression of NHERF1 in normal colon during the
      reproductive cycle of Wistar rats.
AB  - In breast cancer cell lines, the Na(+)/H(+) exchanger regulator factor 1 (NHERF1)
      gene is regulated at the transcriptional level by estrogens, the protein
      expression levels correlate with the presence of estrogen receptors and the
      effect is blocked by anti-estrogens. However, there is limited information
      regarding the regulation of NHERF1 by estrogens in normal colon tissue. The
      NHERF1 protein has an important role in the maintenance of the intestine
      ultrastructure. NHERF1-deficient mice showed defects in the intestinal microvilli
      as well as molecular alterations in brush border membrane proteins. Here, we have
      studied the expression of NHERF1 in normal rat colon and uterus during the
      reproductive cycle of Wistar rats. We found that NHERF1 expression in rat colon
      during the estral cycle is modified by estrogen levels: higher expression of
      NHERF1 was observed during the proestrous and estrous stages and lower expression
      in diestrous 1 when estrogen levels decreased. In uterus, NHERF1 was expressed in
      the apical region of the luminal epithelium and glands in all stages of the
      estral cycle, and in both colon and uterus, the expression was independent of the
      proliferation status. Our results show that NHERF1 expression is regulated by
      estrogens in colon during the rat estral cycle.

PMID- 21079988
TI  - Engagement and Vicarious Traumatization in rescue workers.
AB  - PURPOSE: The aims of this study are (1) to investigate the incidence of the
      symptoms of Vicarious Traumatization in a group of rescue workers; (2) to explore
      some of the main predictors of Engagement and Vicarious Traumatization; and (3)
      to identify the individual and organizational factors able to improve the state
      of well-being of those working in the helping professions. METHODS: A total of
      782 rescue workers, involved in critical operations of various kinds in constant
      contact with traumatized subjects, were investigated applying the Maslach Burnout
      Inventory-General Scale (MBI-GS) and the Secondary Traumatic Stress Scale (STSS).
      RESULTS: The post-traumatic symptoms most frequently reported were those of an
      intrusive nature. A partial overlap emerged between the predictors of Vicarious
      Traumatization and Engagement: if compared with social and demographic
      characteristics and with the degree of commitment required by the work,
      organizational variables would appear to have the greatest influence over the two
      constructs. A supportive working environment in particular favors Engagement,
      reducing the probability of developing Burnout. CONCLUSIONS: The results confirm
      the hypotheses that Engagement and Vicarious Traumatization are primarily
      determined by organizational variables, and, particularly, by the level of job
      support.

PMID- 21079989
TI  - Analysis of a sprint ski race and associated laboratory determinants of world
      class performance.
AB  - This investigation was designed to analyze the time-trial (STT) in an
      international cross-country skiing sprint skating competition for (1) overall STT
      performance and relative contributions of time spent in different sections of
      terrain, (2) work rate and kinematics on uphill terrain, and (3) relationships to
      physiological and kinematic parameters while treadmill roller ski skating. Total
      time and times in nine different sections of terrain by 12 world-class male
      sprint skiers were determined, along with work rate and kinematics for one
      specific uphill section. In addition, peak oxygen uptake (VO(2peak)), gross
      efficiency (GE), peak speed (V(peak)), and kinematics in skating were measured.
      Times on the last two uphill and two final flat sections were correlated to
      overall STT performance (r = ~-0.80, P < 0.001). For the selected uphill section,
      speed was correlated to cycle length (r = -0.75, P < 0.01) and the estimated work
      rate was approximately 160% of peak aerobic power. VO(2peak), GE, V(peak), and
      peak cycle length were all correlated to STT performance (r = ~-0.85, P < 0.001).
      More specifically, VO(2peak) and GE were correlated to the last two uphill and
      two final flat section times, whereas V(peak) and peak cycle length were
      correlated to times in all uphill, flat, and curved sections except for the
      initial section (r = ~-0.80, P < 0.01). Performances on uphill and flat terrain
      in the latter part were the most significant determinants of overall STT
      performance. Peak oxygen uptake, efficiency, peak speed, and peak cycle length
      were strongly correlated to overall STT performance, as well as to performance in
      different sections of the race.

PMID- 21079990
TI  - The impact of different cooling modalities on the physiological responses in
      firefighters during strenuous work performed in high environmental temperatures.
AB  - This study investigated the impact of ice vests and hand/forearm immersion on
      accelerating the physiological recovery between two bouts of strenuous exercise
      in the heat [mean (SD), 49.1(1.3) degrees C, RH 12 (1)]. On four occasions, eight
      firefighters completed two 20-min bouts of treadmill walking (5 km h, 7.5%
      gradient) while wearing standard firefighter protective clothing. Each bout was
      separated by a 15-min recovery period, during which one of four conditions were
      administered: ice vest (VEST), hand/forearm immersion (W), ice vest combined with
      hand/forearm immersion (VEST + W) and control (CON). Core temperature was
      significantly lower at the end of the recovery period in the VEST + W (37.97 +/-
      0.23 degrees C) and W (37.96 +/- 0.19 degrees C) compared with the VEST (38.21 +/
      0.12 degrees C) and CON (38.29 +/- 0.25 degrees C) conditions and remained
      consistently lower throughout the second bout of exercise. Heart rate responses
      during the recovery period and bout 2 were similar between the VEST + W and W
      conditions which were significantly lower compared with the VEST and CON which
      did not differ from each other. Mean skin temperature was significantly lower at
      the start of bout 2 in the cooling conditions compared with CON; these
      differences reduced as exercise progressed. These findings demonstrate that
      hand/forearm immersion (~19 degrees C) is more effective than ice vests in
      reducing the physiological strain when firefighters re-enter structural fires
      after short rest periods. Combining ice vests with hand/forearm immersion
      provides no additional benefit.

PMID- 21079991
TI  - Influence of exercise on nutritional requirements.
AB  - There is no consensus on the best diet for exercise, as many variables influence
      it. We propose an approach that is based on the total energy expenditure of
      exercise and the specific macro- and micronutrients used. di Prampero quantified
      the impact of intensity and duration on the energy cost of exercise. This can be
      used to determine the total energy needs and the balance of fats and
      carbohydrates (CHO). There are metabolic differences between sedentary and
      trained persons, thus the total energy intake to prevent overfeeding of sedentary
      persons and underfeeding athletes is important. During submaximal sustained
      exercise, fat oxidation (FO) plays an important role. This role is diminished and
      CHO's role increases as exercise intensity increases. At super-maximal exercise
      intensities, anaerobic glycolysis dominates. In the case of protein and
      micronutrients, specific recommendations are required. We propose that for
      submaximal exercise, the balance of CHO and fat favors fat for longer exercise
      and CHO for shorter exercise, while always maintaining the minimal requirements
      of each (CHO: 40% and fat: 30%). A case for higher protein (above 15%) as well as
      creatine supplementation for resistance exercise has been proposed. One may also
      consider increasing bicarbonate intake for exercise that relies on anaerobic
      glycolysis, whereas there appears to be little support for antioxidant
      supplementation. Insuring minimal levels of substrate will prevent exercise
      intolerance, while increasing some components may increase exercise tolerance.

PMID- 21079992
TI  - Neuronal morphology in the African elephant (Loxodonta africana) neocortex.
AB  - Virtually nothing is known about the morphology of cortical neurons in the
      elephant. To this end, the current study provides the first documentation of
      neuronal morphology in frontal and occipital regions of the African elephant
      (Loxodonta africana). Cortical tissue from the perfusion-fixed brains of two free
      ranging African elephants was stained with a modified Golgi technique. Neurons of
      different types (N=75), with a focus on superficial (i.e., layers II-III)
      pyramidal neurons, were quantified on a computer-assisted microscopy system using
      Neurolucida software. Qualitatively, elephant neocortex exhibited large, complex
      spiny neurons, many of which differed in morphology/orientation from typical
      primate and rodent pyramidal neurons. Elephant cortex exhibited a V-shaped
      arrangement of bifurcating apical dendritic bundles. Quantitatively, the
      dendrites of superficial pyramidal neurons in elephant frontal cortex were more
      complex than in occipital cortex. In comparison to human supragranular pyramidal
      neurons, elephant superficial pyramidal neurons exhibited similar overall basilar
      dendritic length, but the dendritic segments tended to be longer in the elephant
      with less intricate branching. Finally, elephant aspiny interneurons appeared to
      be morphologically consistent with other eutherian mammals. The current results
      thus elaborate on the evolutionary roots of Afrotherian brain organization and
      highlight unique aspects of neural architecture in elephants.

PMID- 21079993
TI  - Antibody and cytokine responses to hydatid in experimentally infected Kazakh
      sheep with hydatidosis resistance haplotype.
AB  - Different MHC haplotype of Kazakh sheep has different resistance and
      susceptibility of hydatidosis. Notably, the MvaIbc-SacIIab-Hin1Iab haplotype of
      MHC-DRB1 exon two was associated with resistance hydatidosis. In order to analyze
      the antibody and cytokine responses to hydatidosis in Kazakh sheep with
      hydatidosis resistance haplotype, eight Kazakh sheep with the haplotype of MvaIbc
      SacIIab-Hin1Iab were chosen as the test group, and other eight, which were not
      associated with hydatidosis resistance or susceptibility, were taken as control.
      After experimentally infected with hydatid orally, the blood was collected on 0,
      7, 14, 30, 45, 60, 75, 90, 105, and 120 days. Serum and mRNA level of the
      cytokines IL-2, IFN-gamma, TNF-alpha, IL-4, and IL-10 were evaluated by ELISA and
      fluorescence quantitative real-time polymerase chain reaction, respectively. The
      total white blood cells and leukomonocytes were determined by automation
      cytoanalyze. The level of IgE, IgG, and IgM were evaluated by ELISA. The results
      showed that the total white blood cells and leukomonocytes in test group were
      significantly higher than in control on 7, 45, 90, and 105 days post-infection
      (p.i.). The serum level of IL-2 in test group was significantly higher than in
      control on 45 days p.i., while the difference of IL-2 mRNA expression between
      test and control group was not significant. The serum level of TNF-alpha in test
      group was significantly higher than in control at 90 and 105 days p.i., and the
      TNF-alpha mRNA in test group was also significantly higher than in control on 90
      days p.i. The level of IgE, IgG, and IgM in test group was higher than in
      control, but none was significant. The results suggested that the test group,
      which was predominant of Th1, could induce the protective immunity, while the
      control, which was predominant of Th2, could induce the susceptibility to
      infection of hydatidosis.

PMID- 21079994
TI  - Antiplasmodial activity of botanical extracts against Plasmodium falciparum.
AB  - The absence of a vaccine and the rampant resistance to almost all antimalarial
      drugs have accentuated the urgent need for new antimalarial drugs and drug
      targets for both prophylaxis and chemotherapy. The aim of the study was to
      discover effective plant extracts against Plasmodium falciparum. In the present
      study, the hexane, chloroform, ethyl acetate, acetone, and methanol extracts of
      Citrus sinensis (peel), Leucas aspera, Ocimum sanctum, Phyllanthus acidus (leaf),
      Terminalia chebula (seed) were tested for their antimalarial activity against
      chloroquine (CQ)-sensitive (3D7) strain of P. falciparum which was cultured
      following the candle-jar method. Antimalarial evaluations of daily replacement of
      culture medium containing CQ and different plant crude extracts were performed on
      96-well plates at 37 degrees C for 24 and 48 h. Parasitemia was determined
      microscopically on thin-film Giemsa-stained preparations. Plant extracts were
      tested for their cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay on human laryngeal cancer cell line (HEp-2) and
      normal cell line (Vero). Out of the 25 extracts tested, six showed good (IC(50)
      4.76-22.76 MUg/mL), 15 exhibited moderate (IC(50) 31.42-88.03 MUg/mL), while four
      displayed mild (IC(50) > 100 MUg/mL) antiplasmodial activity. The leaf ethyl
      acetate and methanol extracts of L. aspera; ethyl acetate, acetone, and methanol
      extracts of P. acidus; and seed acetone extract of T. chebula had good
      antiplasmodial activity (IC(50) = 7.81, 22.76, 9.37, 14.65, 12.68, and 4.76
      MUg/mL) with selectivity indices 5.43, 2.04, 4.88, 3.35, 3.42, and 9.97 for HEp-2
      and >5.79, >2.20, >11.75, >3.41, >3.94, and >7.38 for Vero cells, respectively.
      These analyses have revealed for the first time that the components present in
      the solvent extracts of L. aspera, P. acidus, and T. chebula have antiplasmodial
      activity. The high antiplasmodial activity observed make these plants good
      candidates for isolation of anti-protozoal compounds which could serve as new
      lead structures for drug development.

PMID- 21079995
TI  - Prevalence of antibodies against Neospora caninum in dogs from urban areas in
      Central Poland.
AB  - Neospora caninum is a protozoan parasite which causes abortion in cattle as well
      as reproduction problems and neurological disorders in dogs. To assess the
      prevalence of the parasite in urban dogs in the Mazovian Voivodeship, Central
      Poland, serum samples from 257 dogs were analyzed for the presence of specific
      IgG antibodies. The examined dogs visited three private veterinary clinics
      located in Warsaw due to control tests, vaccinations, or other reasons not
      directly connected with neosporosis. Using ELISA and Western blot, antibodies
      against the parasite were detected in 56 out of 257 dogs, giving a prevalence of
      21.7%. A greater prevalence was observed in female dogs than in males, 28% and
      17.3%, respectively, and the differences were statistically significant (p<0.05).
      There were no significant differences in seroprevalence of Neospora infection
      within the age groups (p>0.05). This study indicates the presence of N. caninum
      in the Mazovian Voivodeship, in dogs which live in urban areas and exposure of
      these dogs to the parasite. The fact that seropositive dogs had no contact with
      cattle confirms the important role of dogs in the parasite's epidemiology.

PMID- 21079996
TI  - Identification and experimental validation of G protein alpha inhibiting activity
      polypeptide 2 (GNAI2) as a microRNA-138 target in tongue squamous cell carcinoma.
AB  - MicroRNA deregulation is a critical event in tumor initiation and progression.
      The down-regulation of microRNA-138 has been frequently observed in various
      cancers, including tongue squamous cell carcinoma (TSCC). Our previous studies
      suggest that deregulation of miR-138 is associated with the enhanced
      proliferation and invasion in TSCC cells. Here, we seek to identify the targets
      of miR-138 in TSCC, and explore their functional relevance in tumorigenesis. Our
      genome-wide expression profiling experiments identified a panel of 194 unique
      transcripts that were significantly down-regulated in TSCC cells transfected with
      miR-138. A comprehensive screening using six different sequence-based microRNA
      target prediction algorithms revealed that 51 out of these 194 down-regulated
      transcripts are potential direct targets for miR-138. These targets include:
      chloride channel, nucleotide-sensitive, 1A (CLNS1A), G protein alpha inhibiting
      activity polypeptide 2 (GNAI2), solute carrier family 20, member 1 (SLC20A1),
      eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), and Rho
      related GTP-binding protein C (RhoC). GNAI2 is a known proto-oncogene that is
      involved in the initiation and progression of several different types of tumors.
      Direct targeting of miR-138 to two candidate binding sequences located in the 3'
      untranslated region of GNAI2 mRNA was confirmed using luciferase reporter gene
      assays. Knockdown of miR-138 in TSCC cells enhanced the expression of GNAI2 at
      both mRNA and protein levels. In contrast, ectopic transfection of miR-138
      reduced the expression of GNAI2, which, in consequence, led to reduced
      proliferation, cell cycle arrest and apoptosis. In summary, we identified a
      number of high-confident miR-138 target genes, including proto-oncogene GNAI2,
      which may play an important role in TSCC initiation and progression.

PMID- 21079997
TI  - Uncovering hidden variance: pair-wise SNP analysis accounts for additional
      variance in nicotine dependence.
AB  - Results from genome-wide association studies of complex traits account for only a
      modest proportion of the trait variance predicted to be due to genetics. We
      hypothesize that joint analysis of polymorphisms may account for more variance.
      We evaluated this hypothesis on a case-control smoking phenotype by examining
      pairs of nicotinic receptor single-nucleotide polymorphisms (SNPs) using the
      Restricted Partition Method (RPM) on data from the Collaborative Genetic Study of
      Nicotine Dependence (COGEND). We found evidence of joint effects that increase
      explained variance. Four signals identified in COGEND were testable in
      independent American Cancer Society (ACS) data, and three of the four signals
      replicated. Our results highlight two important lessons: joint effects that
      increase the explained variance are not limited to loci displaying substantial
      main effects, and joint effects need not display a significant interaction term
      in a logistic regression model. These results suggest that the joint analyses of
      variants may indeed account for part of the genetic variance left unexplained by
      single SNP analyses. Methodologies that limit analyses of joint effects to
      variants that demonstrate association in single SNP analyses, or require a
      significant interaction term, will likely miss important joint effects.

PMID- 21079998
TI  - Localization of three types of arginine vasotocin receptors in the brain and
      pituitary of the newt Cynops pyrrhogaster.
AB  - The distribution of three types of arginine vasotocin (AVT) receptors in the
      brain and pituitary of the newt Cynops pyrrhogaster, namely, the V1a-, V2-, and
      V3/V1b-type receptors, was studied by means of in situ hybridization and
      immunohistochemistry. mRNA signals and immunoreactive cells for the V1a-type
      receptor were observed in the telencephalon (mitral layer of the olfactory bulb,
      dorsal and medial pallium, lateral and medial amygdala, bed nucleus of the
      decussation of the fasciculus telencephali, bed nucleus of the stria terminalis),
      diencephalon (anterior preoptic area, magnocellular preoptic nucleus,
      suprachiasmatic nucleus, ventral thalamus, dorsal and ventral hypothalamic
      nucleus), mesencephalon (tegmentum, interpeduncular nucleus), and medulla
      oblongata (median reticular formation, nucleus motorius tegmenti). Cells
      expressing the V2-type receptor were found in the telencephalon (medial pallium,
      lateral and medial amygdala, bed nucleus of the decussation of the fasciculus
      telencephali), and mesencephalon (tegmentum trigemini and facialis). In the
      paraphysis (possibly the main site of cerebrospinal fluid production), only V2
      type receptor mRNA signal and immunoreactivity were detected. V3/V1b-type
      receptor mRNA was expressed in the diencephalon (dorsal hypothalamic nucleus,
      nucleus tuberculi posterioris), mesencephalon (tegmentum, interpeduncular
      nucleus), and medulla oblongata (raphe nucleus), whereas V3/V1b-type-receptor
      like immunoreactivity was scarcely detectable in the entire brain. The V3/V1b
      type receptor was predominantly expressed in the anterior pituitary. V3/V1b-type
      receptor and proopiomelanocortin mRNAs were co-localized in the distal lobe of
      the pituitary. This is the first report of the distribution of three types of AVT
      receptor in the brain and pituitary of non-mammalian vertebrates.

PMID- 21079999
TI  - Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an
      ichthyosis-vulgaris-like disease.
AB  - The skin is the outer layer of protection against the environment. The
      development and formation of the skin is regulated by several genetic cascades
      including the bone morphogenetic protein (BMP) signaling pathway, which has been
      suggested to play an important role during embryonic organ development. Several
      skin defects and diseases are caused by genetic mutations or disorders.
      Ichthyosis is a common genetic skin disorder characterized by dry scaly skin.
      Loss-of-function mutations in the filaggrin (FLG) gene have been identified as
      the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct
      regulation of filaggrin expression in vivo is unknown. We present evidence that
      BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a
      constitutively active form of BMP-receptor-IB in the developing epidermis exhibit
      a phenotype resembling IV in humans, including dry flaky skin, compact
      hyperkeratosis, and an attenuated granular layer associated with a significantly
      downregulated expression of filaggrin. Regulation of filaggrin expression by BMP
      signaling has been further confirmed by the application of exogenous BMP2 in skin
      explants and by a transgenic model overexpressing Noggin in the epidermis. Our
      results demonstrate that aberrant BMP signaling in the epidermis causes
      overproliferation and hyperkeratinization, leading to an IV-like skin disease.

PMID- 21080001
TI  - Dendritic spine abnormalities in mental retardation.
AB  - Abnormalities in dendritic spine morphologies are often associated with mental
      retardation. Since dendritic spines are thought to represent a morphological
      correlate of neuronal plasticity, altered spine morphologies may underlie or
      contribute to cognitive deficits seen in mental retardation. Signaling cascades
      that are important for cytoskeletal regulation may have an impact upon spine
      morphologies. The Rho GTPase signaling pathway has been shown to be involved in
      the regulation of the cytoskeleton and to play fundamental roles in the
      structural plasticity of dendritic spines. Moreover, alterations in the Rho
      GTPase signaling pathway have been shown to contribute to mental retardation.
      Recently, different mental retardation-associated genes have been identified that
      encode modulators of the Rho GTPases. Disturbances in these genes can lead to
      mental retardation and-on the morphological level-to alterations in dendritic
      spines. Thus, getting more insight into the Rho GTPase signaling pathways, and
      the molecules involved, would not only help in understanding the basic mechanisms
      by which the morphologies of dendritic spines are modulated but may also allow
      the development of therapeutic strategies to counteract some aspects of mental
      retardation.

PMID- 21080000
TI  - The Ca(2+)-binding protein calretinin is selectively enriched in a subpopulation
      of the epithelial rests of Malassez.
AB  - During tooth development, the inner and outer enamel epithelia fuse by mitotic
      activity to produce a bilayered epithelial sheath termed Hertwig's epithelial
      root sheath (HERS). The epithelial rests of Malassez (ERM) are the developmental
      residues of HERS and remain in the adult periodontal ligament (PDL). Although the
      cellular regulation of the Ca(2+)-binding proteins parvalbumin, calbindin-D28k,
      and calretinin has been reported in the inner and outer enamel epithelia during
      tooth development, an involvement of Ca(2+)-binding proteins in the ERM has not
      so far been characterized. Among the three Ca(2+)-binding proteins tested
      (calbindin D28k, parvalbumin, calretinin), we have only been able to detect
      calretinin in a subpopulation of adult rat molar ERM, by using quantitative
      immunohistochemical and confocal immunofluorescence techniques. TrkA (a marker
      for ERM) is present in numerous epithelial cell clusters, whereas calretinin has
      been localized in the cytosol and perinuclear region of a subpopulation of TrkA
      positive cells. We conclude that, in inner and outer enamel epithelial cells,
      Ca(2+) is regulated by calbindin, parvalbumin, and calretinin during tooth
      development, whereas in the ERM of adult PDL, Ca(2+) is regulated only by
      calretinin. The expression of Ca(2+)-binding proteins is restricted in a
      developmental manner in the ERM.

PMID- 21080002
TI  - Effect of within-species plant genotype mixing on habitat preference of a
      polyphagous insect predator.
AB  - The effects of within-species plant genotype mixing on the habitat preference of
      a polyphagous ladybird were studied. Plant species diversity is often claimed to
      positively affect habitat preferences of insect predators, but the effects of
      within-species genotype diversity have not been extensively studied. In a field
      experiment with different barley (Hordeum vulgare) genotypes in mixed and pure
      stands, adult seven-spot ladybird Coccinella septempunctata, a polyphagous
      predator, preferred a specific combination of genotypes over the single genotypes
      alone before aphids had arrived in the crop, and again when aphids were
      emigrating. In laboratory experiments on adult ladybird orientation to odour from
      barley, ladybirds were attracted/arrested by the mixed odour of the same barley
      genotype mixture that was preferred in the field. Exposure of one barley genotype
      to volatiles from the other also caused the odour of the exposed plants to become
      more attractive to ladybirds. The results support the hypothesis that plant
      volatiles may attract or arrest foraging adult ladybirds, contributing to the
      selection of favourable habitats, and they show that within-species plant
      genotype mixing can shape interactions within multitrophic communities.

PMID- 21080004
TI  - Human body area factors for radiation exchange analysis: standing and walking
      postures.
AB  - Effective radiation area factors (f (eff)) and projected area factors (f (p)) of
      unclothed Caucasians' standing and walking postures used in estimating human
      radiation exchange with the surrounding environment were determined from a sample
      of adults in Canada. Several three-dimensional (3D) computer body models were
      created for standing and walking postures. Only small differences in f (eff) and
      f (p) values for standing posture were found between gender (male or female) and
      body type (normal- or over-weight). Differences between this study and previous
      studies were much larger: <=0.173 in f (p) and <=0.101 in f (eff). Directionless
      f (p) values for walking posture also had only minor differences between genders
      and positions in a stride. However, the differences of mean directional f (p)
      values of the positions dependent on azimuth angles were large enough, <=0.072,
      to create important differences in modeled radiation receipt. Differences in f
      (eff) values were small: 0.02 between the normal-weight male and female models
      and up to 0.033 between positions in a stride. Variations of directional f (p)
      values depending on solar altitudes for walking posture were narrower than those
      for standing posture. When both standing and walking postures are considered, the
      mean f (eff) value, 0.836, of standing (0.826) and walking (0.846) could be used.
      However, f (p) values should be selected carefully because differences between
      directional and directionless f (p) values were large enough that they could
      influence the estimated level of human thermal sensation.

PMID- 21080003
TI  - Uraemic vasculopathy in children with chronic kidney disease: prevention or
      damage limitation?
AB  - Since the inception of pediatric dialysis programmes nearly 50 years ago, there
      have been vast improvements in both the technology and expertise in the care of
      children with chronic kidney disease (CKD). Nevertheless, children on dialysis
      continue to have a significantly higher mortality than their healthy peers and
      cardiovascular disease (CVD) is the most common cause of death in this group.
      Chronic kidney disease is described as the "perfect storm" of risk factors for
      CVD development, and vascular calcification is a highly regulated cell-mediated
      process with several promoters and inhibitors of calcification. CVD begins early
      in the course of CKD and there is an independent and graded association between
      cardiovascular morbidity and renal decline. Also, it is shown that once vascular
      damage and calcification begin, they progress inexorably in the uraemic milieu
      and may only be partially reversed after successful transplantation. Thus,
      preventing the development of CVD is key, and early identification and management
      of specific CVD-related risk factors should begin from the early stages of CKD.
      While the vasculopathy of childhood CKD is clearly multifactorial, clinical,
      epidemiological and cell biology studies provide converging evidence pointing to
      the role of dysregulated mineral metabolism as an important modifiable risk
      factor in the development of vascular calcification. In this review we focus on
      the role of calcium, phosphate, parathyroid hormone and vitamin D in ectopic
      vascular calcification, and discuss the role of screening, early intervention and
      management of established vascular calcification.

PMID- 21080005
TI  - G6PD deficiency-induced hemolysis in a Chinese diabetic patient: a case report
      with clinical and molecular analysis.
AB  - A 59-year-old Chinese male patient was admitted at diagnosis of type 1 diabetes
      with ketoacidosis. During the normalization of blood glucose with insulin, the
      patient developed acute hemolysis. The factors predisposing to hemolysis were not
      found, except the significantly diminished activity of glucose-6-phosphate
      dehydrogenase (G6PD). DNA analysis did not show any coding or intronic mutation
      in the G6PD gene. This is the first reported case of a Chinese patient in
      diabetic ketoacidosis with hemolysis induced by G6PD deficiency in the absence of
      mutations in the G6PD gene.

PMID- 21080006
TI  - Health-related quality of life following spinal cordectomy for syringomyelia.
AB  - BACKGROUND: Spinal cordectomy has been described as an effective treatment option
      in paraplegic patients for the treatment of syringomyelia to manage spasticity,
      pain and ascending neurological dysfunction. The objective of this study was to
      investigate the long-term health-related quality of life (HRQoL) after cordectomy
      in patients with intractable symptoms caused by syringomyelia. METHODS: Seventeen
      patients underwent spinal cordectomy for syringomyelia between February 2000 and
      July 2009. The etiology of syringomyelia was traumatic in 16 patients and spinal
      ependymoma in one patient. The mean follow-up was 3.8 years (range, 0.9-10.3).
      The HRQoL was assessed pre- and postoperatively using the EuroQol (EQ; degree of
      discomfort: 1 = none, 2 = moderate and 3 = extreme) and the short-form SF-36
      quality of life score (SF-36). All patients underwent a telephone interview.
      RESULTS: The mean pre- and postoperative EuroQol-levels for mobility were 1.8 and
      1.5; for self-care, 1.9 and 1.5; for usual activities, 2.1 and 1.5; for
      pain/discomfort, 2.3 and 2.0; and for anxiety/depression, 1.7 and 1.5,
      respectively. The mean overall EQ visual analogue scale improved postoperatively
      from 42 points (range, 15-80) to 67 points (range, 10-95) (p = 0.006). The
      component summary measure for mental health (SF-36) significantly improved
      postoperatively (p = 0.01). A telephone interview revealed a high subjective
      patient satisfactory (94.1%) in terms of postoperative sequelae. Following the
      intervention, 58.8% of all patients were employed full or part-time. CONCLUSIONS:
      Spinal cordectomy may increase the quality of life and can be considered as an
      ultimo ratio therapy in a selective group of patients with intractable symptoms
      caused by syringomyelia.

PMID- 21080008
TI  - Computerized angiographic evaluation of coil density and occlusion rate in
      embolized cerebral aneurysms.

PMID- 21080009
TI  - Rotigotine transdermal system for control of early morning motor impairment and
      sleep disturbances in patients with Parkinson's disease.
AB  - This open-label study (NCT00243945) investigated the efficacy of rotigotine
      transdermal system in 54 Parkinson's disease (PD) patients with unsatisfactory
      control of early morning motor impairment and sleep disturbances. Rotigotine dose
      was up titrated for 8 weeks and maintained for 4 weeks. Mean rotigotine dose at
      end of maintenance was 11.83 mg/24 h (SD 3.86). Patients had two overnight
      hospital stays at baseline and end of treatment during which early morning motor
      performance was assessed, prior to first morning dose of regular oral
      antiparkinsonian medication. Rotigotine improved mean Unified Parkinson's Disease
      Rating Scale (UPDRS) part III score by -9.3 points, mean Timed Up and Go test
      duration by -1.4 s and mean morning finger tapping by 26.5 taps/min; 46% of
      patients were considered responders (>=30% improvement of UPDRS III). Mean
      Nocturnal Akinesia, Dystonia and Cramps Sum Score was reduced by 61%; mean number
      of nocturias decreased by 32%. Rotigotine also improved sleep quality. These
      results suggest a role for rotigotine in treatment of nocturnal and early morning
      motor disabilities in PD patients.

PMID- 21080011
TI  - Amborella trichopoda, plasmodesmata, and the evolution of phloem loading.
AB  - Phloem loading is the process by which photoassimilates synthesized in the
      mesophyll cells of leaves enter the sieve elements and companion cells of minor
      veins in preparation for long distance transport to sink organs. Three loading
      strategies have been described: active loading from the apoplast, passive loading
      via the symplast, and passive symplastic transfer followed by polymer trapping of
      raffinose and stachyose. We studied phloem loading in Amborella trichopoda, a
      premontane shrub that may be sister to all other flowering plants. The minor
      veins of A. trichopoda contain intermediary cells, indicative of the polymer trap
      mechanism, forming an arc on the abaxial side and subtending a cluster of
      ordinary companion cells in the interior of the veins. Intermediary cells are
      linked to bundle sheath cells by highly abundant plasmodesmata whereas ordinary
      companion cells have few plasmodesmata, characteristic of phloem that loads from
      the apoplast. Intermediary cells, ordinary companion cells, and sieve elements
      form symplastically connected complexes. Leaves provided with (14)CO(2)
      translocate radiolabeled sucrose, raffinose, and stachyose. Therefore, structural
      and physiological evidence suggests that both apoplastic and polymer trapping
      mechanisms of phloem loading operate in A. trichopoda. The evolution of phloem
      loading strategies is complex and may be difficult to resolve.

PMID- 21080012
TI  - CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic
      prodrug.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder associated primarily
      with loss of dopamine (DA) neurons in the nigrostriatal system. With the aim of
      increasing the bioavailability of L: -dopa (LD) after oral administration and of
      overcoming the pro-oxidant effect associated with LD therapy, we designed a
      peptidomimetic LD prodrug (1) able to release the active agent by enzyme
      catalyzed hydrolysis. The physicochemical properties, as well as the chemical and
      enzymatic stabilities of the new compound, were evaluated in order to check both
      its stability in aqueous medium and its sensitivity towards enzymatic cleavage,
      providing the parent LD drug, in rat and human plasma. The radical scavenging
      activities of prodrug 1 was tested by using both the DPPH-HPLC and the DMSO
      competition methods. The results indicate that the replacement of cysteine GSH
      portion by methionine confers resistance to oxidative degradation in gastric
      fluid. Prodrug 1 demonstrated to induce sustained delivery of DA in rat striatal
      tissue with respect to equimolar LD dosages. These results are of significance
      for prospective therapeutic application of prodrug 1 in pathological events
      associated with free radical damage and decreasing DA concentration in the brain.

PMID- 21080013
TI  - Comparative study of the interaction of synthetic methionine-enkephalin and its
      amidated derivate with monolayers of zwitterionic and negatively charged
      phospholipids.
AB  - Using Langmuir's monolayer technique, the surface behavior and the interaction of
      the synthetic neuropeptide methionine-enkephalin (Met-enk) and its amidated
      derivate (Met-enk-NH(2)) with monolayers of the zwitterionic
      dimyristoylphosphatidylcholine (DMPC) and the negatively charged
      dimyristoylphosphatidylglycerol (DMPG) were studied. The surface tension (gamma,
      mN/m) of DMPG and DMPC monolayers as a function of time (after injection of the
      peptide under the interface) was detected. The decrease in gamma values showed
      that there was a strong penetration effect of both types of Met-enk molecules
      into the monolayers, being significantly stronger for the amidated derivate, Met
      enk-NH(2). We suggest that the interaction between the neuropeptides and DMPC was
      predominantly determined by peptides amphiphilicity, while the electrostatic
      forces play significant role for the insertion of the cationic Met-enk-NH(2) in
      DMPG monolayers, especially at high packing densities. Our results demonstrate
      the potential of lipid monolayers formed in Langmuir's trough to be successfully
      used as an elegant and simple membrane models to study lipid-peptide interactions
      at the air/water interface.

PMID- 21080014
TI  - Lignin-derived oak phenolics: a theoretical examination of additional potential
      health benefits of red wine.
AB  - Lignin-derived phenolic compounds can be extracted from oak barrels during the
      aging of red wine, and it is hypothesized that these compounds may contribute to
      the health benefits of red wine by their antioxidant, radical-scavenging, or
      chemopreventive activities. Density functional calculations (B3LYP/6-311++G)
      support the radical-scavenging abilities of the oak phenolics. Sinapaldehyde,
      syringaldehyde, syringol, and syringylacetone all have bond dissociation energies
      that are lower than resveratrol and comparable to the flavonoid catechin.
      Molecular docking studies of the oak phenolics with known resveratrol protein
      targets also show that these compounds dock favorably to the protein targets.
      Thus, lignin-derived oak phenolics, although found in small concentrations, may
      contribute to the beneficial antioxidant, chemopreventive, and cardioprotective
      effects of red wine.

PMID- 21080015
TI  - A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV
      drugs.
AB  - Molecular docking is a reliable method with which to identify the binding
      conformations of substrates, inducers and inhibitors of cytochrome P450 (CYP)
      enzymes. We used the docking method to explore possible binding modes of an entry
      inhibitor (maraviroc) and non-nucleoside reverse transcriptase inhibitors
      (delavirdine, efavirenz and etravirine) to cytochrome P450 3A4 (CYP3A4). In
      addition, docking results were compared with the binding conformations of HIV
      protease drugs to infer the binding site residues and potential drug-drug
      interaction profiles for combination therapy in the treatment of AIDS. We
      observed that efavirenz and etravirine induce metabolism of co-administered drugs
      by binding to a unique position in the active site of CYP3A4. Dosage adjustment
      is required for delavirdine and maraviroc when combined with HIV protease drugs.
      The present results are in good agreement with experimental data from drug
      interaction profiles. The information provided in this paper will be helpful in
      furthering our understanding the functions of CYP3A4, and could aid in the design
      of new drugs that would be metabolized easily without having any drug-drug
      interaction profile.

PMID- 21080016
TI  - Biological and docking studies of topoisomerase IV inhibition by
      thiosemicarbazides.
AB  - 4-Benzoyl-1-(4-methyl-imidazol-5-yl)-carbonylthiosemicarbazide (1) was
      synthesized, and its antibacterial and type IIA topoisomerase (DNA gyrase and
      topoisomerase IV) activity evaluated. (1) was found to have high therapeutic
      potential against opportunistic Gram-positive bacteria, and inhibitory activity
      against topoisomerase IV (IC(50)=90 MUM) but not against DNA gyrase. An increase
      in activity against topoisomerase IV (IC(50)=14 MUM) was observed when the
      imidazole moiety of (1) was replaced with the indole group in 4-benzoyl-1-(indol
      2-yl)-carbonylthiosemicarbazide (2). However, (2) showed only weak antibacterial
      activity. Although the results of the bacterial type IIA topoisomerases
      inhibition study did not parallel antibacterial activities, our observations
      strongly imply that a 4-benzoylthiosemicarbazide scaffold can be developed into
      an efficient Gram-positive antibacterial targeting topoisomerase IV. The
      difference in activity against type IIA topoisomerases between (1) and (2) was
      further investigated by docking studies, which suggested that these compounds
      target the ATP binding pocket.

PMID- 21080017
TI  - Effect of alkyl substitution on H-bond strength of substituted amide-alcohol
      complexes.
AB  - The effect of alkyl substitution (CH3, C2H5, n-C3H7, i-C3H7, and t-C4H9) on the
      hydrogen bond strengths (H-bond) of substituted amide-alcohol complexes has been
      systematically explored. B3LYP/aug-cc-pVDZ method was applied to a total of 215
      alkyl substituted amide-alcohol complexes to delineate the effect of substitution
      on the H-bond strength; formamide-water complex is taken as reference point.
      Complexes are classified into five types depending on the hydrogen donor,
      acceptor and the site of alkyl substitution (Type-IA, Type-IIA, Type-IB, Type-IIB
      and Type-III). The strength of H-bond was correlated with geometrical parameters
      such as proton-acceptor (H????Y) distance, the length of proton donating bond (X
      H). In all the complexes N-H and O-H stretching frequencies are red-shifted. The
      effect of alkyl substitution on N-H and O-H stretching frequencies were analyzed.
      Topological parameters like electron density at H????Y and X-H bond critical
      points as derived from atom in molecules (AIM) theory was also evaluated. When C
      = O group is participating in H-bond, the strength of H-bond decreases with
      increasing size of alcohols except for methanol (Type-IA, Type-III and Type-IB
      complexes). But it increases with increasing size of alkyl groups on amide and
      decreases with bulky groups. In the case of N-H group as H-bond donor, the
      strength of H-bond increases with increasing size of alcohols (Type-IIA and Type
      IIB complexes) whereas decreases with increasing size of alkyl groups on amide.
      Type-IA, IIA, IB and IIB complexes exhibit good correlations among IE, H-bond
      distance and electron density at bcp. In Type-III complexes, average H-bond
      distance and sum of electron densities shows better correlation with IEs than the
      corresponding individuals. The correlation of IE less with electron density at
      RCP compared to sum of electron densities.

PMID- 21080018
TI  - Homology modeling and molecular dynamics simulations of MUC1-9/H-2K(b) complex
      suggest novel binding interactions.
AB  - Human MUC1 is over-expressed in human adenocarcinomas and has been used as a
      target for immunotherapy studies. The 9-mer MUC1-9 peptide has been identified as
      one of the peptides which binds to murine MHC class I H-2K(b). The structure of
      MUC1-9 in complex with H-2K(b) has been modeled and simulated with classical
      molecular dynamics, based on the x-ray structure of the SEV9 peptide/H-2K(b)
      complex. Two independent trajectories with the solvated complex (10 ns in length)
      were produced. Approximately 12 hydrogen bonds were identified during both
      trajectories to contribute to peptide/MHC complex, as well as 1-2 water mediated
      hydrogen bonds. Stability of the complex was also confirmed by buried surface
      area analysis, although the corresponding values were about 20% lower than those
      of the original x-ray structure. Interestingly, a bulged conformation of the
      peptide's central region, partially characterized as a beta-turn, was found
      exposed form the binding groove. In addition, P1 and P9 residues remained bound
      in the A and F binding pockets, even though there was a suggestion that P9 was
      more flexible. The complex lacked numerous water mediated hydrogen bonds that
      were present in the reference peptide x-ray structure. Moreover, local
      displacements of residues Asp4, Thr5 and Pro9 resulted in loss of some key
      interactions with the MHC molecule. This might explain the reduced affinity of
      the MUC1-9 peptide, relatively to SEV9, for the MHC class I H-2K(b).

PMID- 21080019
TI  - Atomistic simulations of materials for optical chemical sensors: DFT-D
      calculations of molecular interactions between gas-phase analyte molecules and
      simple substrate models.
AB  - The structures of complexes of some small molecules (formaldehyde, acetaldehyde,
      ammonia, methylamine, methanol, ethanol, acetone, benzene, acetonitrile, ethyl
      acetate, chloroform, and tetrahydrofuran, considered as possible analytes) with
      ethylbenzene and silanol (C(6)H(5)C(2)H(5) and SiH(3)OH, considered as models of
      polystyrene and silica gel substrates) and with acridine (C(13)H(9)N, considered
      as a model of an indicator dye molecule of the acridine series) and the
      corresponding interaction energies have been calculated using the DFT-D
      approximation. The PBE exchange-correlation potential was used in the
      calculations. The structures of complexes between the analyte and the substrate
      were determined by optimizing their ground-state geometry using the SVP split
      valence double-zeta plus polarization basis set. The complex formation energies
      were refined by single-point calculations at the calculated equilibrium
      geometries using the sufficiently large triple-zeta TZVPP basis set. The
      calculated interaction energies are used to assess the possibility of using dyes
      of the acridine series adsorbed on a polystyrene or silica substrate for
      detecting the small molecules listed above.

PMID- 21080020
TI  - Supramolecular synthon pattern in solid clioquinol and cloxiquine (APIs of
      antibacterial, antifungal, antiaging and antituberculosis drugs) studied by 35Cl
      NQR, 1H-17O and 1H-14N NQDR and DFT/QTAIM.
AB  - The quinolinol derivatives clioquinol (5-chloro-7-iodo-8-quinolinol, Quinoform)
      and cloxiquine (5-chloro-8-quinolinol) were studied experimentally in the solid
      state via 35Cl NQR, 1H-17O and 1H-14N NQDR spectroscopies, and theoretically by
      density functional theory (DFT). The supramolecular synthon pattern of O-H...N
      hydrogen bonds linking dimers and pi-pi stacking interactions were described
      within the QTAIM (quantum theory of atoms in molecules) /DFT (density functional
      theory) formalism. Both proton donor and acceptor sites in O-H...N bonds were
      characterized using 1H-17O and 1H-14N NQDR spectroscopies and QTAIM. The
      possibility of the existence of O-H...H-O dihydrogen bonds was excluded. The weak
      intermolecular interactions in the crystals of clioquinol and cloxiquine were
      detected and examined. The results obtained in this work suggest that
      considerable differences in the NQR parameters for the planar and twisted
      supramolecular synthons permit differentiation between specific polymorphic
      forms, and indicate that the more planar supramolecular synthons are accompanied
      by a greater number of weaker hydrogen bonds linking them and stronger pi...pi
      stacking interactions.

PMID- 21080021
TI  - Can simple ultrasonography predict the clinical effect of intra-articular
      injection therapy of the knee joint?
AB  - To investigate whether ultrasonographic joint assessment can predict the clinical
      response to intra-articular injection therapy of the knee. Patients with
      persistent gonarthritis intra-articularly received in a randomized double-blinded
      crossover fashion radiation synovectomy or a glucocorticoid injection, both
      followed by clinical bed rest. Prior to treatment and 3 months afterwards, grey
      scale ultrasonography (US) of the knee was performed, measuring synovial
      thickness and extent of effusion. The final clinical effect of these two
      treatments was assessed at 3 months and finally at 6 months using a composite
      index. Ninety-seven patients, mainly suffering from undifferentiated arthritis
      (40%) or rheumatoid arthritis (31%), received 165 injections (including
      crossovers). Clinical effect at 6 months was not related to the baseline
      ultrasonographic extent of effusion or synovial thickness, nor with
      ultrasonographic decrease of effusion after the first 3 months. Nevertheless, it
      was associated with ultrasonographic decrease of synovial thickness within the
      first 3 months. Simple baseline US measurements fail to predict the final
      clinical effect of intra-articular treatment of the knee at 6 months, in contrast
      to early US changes of synovial thickness 3 months after therapy.

PMID- 21080022
TI  - How frequent is varicella-associated pneumonia in children?
AB  - Varicella is a frequent though mild infection in children, but it can cause
      important morbidity in adults. The most frequent complication in adults is
      varicella pneumonia. However, lower airway complications associated to varicella
      have been scarcely studied in children. We retrospectively reviewed the clinical
      records of the children hospitalized for varicella-associated pneumonia in the
      three public hospitals on the Island of Mallorca. We discovered that 17/213 (8%)
      children hospitalized for varicella were diagnosed of pneumonia. The rate of
      hospitalization for varicella complication due to pneumonia was 4.3 cases per
      10,000 varicella infections. Only one patient was diagnosed of varicella
      pneumonia, which accounts for 0.3 cases per 10,000 varicella infections. Nine of
      17 (53%) cases were classified as bacterial pneumonia. Statistical differences (p
      < 0.05) in the median time from rash (5.9 vs. 2.4 days) and fever (4.1 vs. 2.2
      days) to admission were observed between bacterial and viral pneumonia. However,
      outcome differences measured by the median length of stay, need for oxygen, and
      admission to the intensive care unit were not observed. Varicella pneumonia is a
      very rare complication of varicella in children. Most of the lower airway
      infections in the course of varicella are associated to other co-infections.

PMID- 21080023
TI  - Lifting the burden: the first 7 years.

PMID- 21080024
TI  - The cost of multiple sclerosis in Norway.
AB  - Health economic aspects have been increasingly important during introduction of
      new treatments for multiple sclerosis. As a partial response for Norway, a cost
      of-illness study was carried out to estimate the yearly cost of the illness to
      society and relate costs and patients' quality of life to illness severity.
      Estimated cost to society was Euro 439 million in 2002 exclusive of the cost of
      reduced quality of life. The cost per patient was close to Euro 65,000. Account
      taken of methodological differences, the results compare to results for Sweden,
      Norway's closest neighboring country. The illness reduced patients' quality of
      life with 0.26. More patients were early retired because of their MS in Norway
      than in any of nine other European countries comprised by a recent European
      study, illustrating a liberal practice in Norway. The Norwegian cost of unpaid
      assistance was almost identical to the Swedish cost that was the lowest found
      across the countries in the European study. When related to illness severity, the
      cost per patient increased, and the patients' experienced quality of life
      decreased with increasing EDSS levels in line with what has been found for other
      countries. Cost-of-MS studies have been carried out for a number of countries.
      Together they contribute to our understanding of the economic consequences of
      multiple sclerosis and, if their results are related to illness severity, also
      provide valuable information for further economic analyses of treatment and
      medication. Our study adds to this.

PMID- 21080025
TI  - Changes in autonomic balance in patients with decompensated chronic heart
      failure.
AB  - OBJECTIVE: In chronic heart failure (CHF) episodes of decompensation may be
      linked to derangements within cardiovascular reflex control. We investigated
      changes in autonomic tone in patients with decompensated CHF. METHODS: We
      examined 17 patients with decompensated CHF (14 men, age 62 +/- 2 years, LVEF 32
      +/- 3%) on admission and after clinical stabilization. Control group consisted of
      9 patients (8 men, age 64 +/- 7 years, LVEF 30 +/- 7%) with stable CHF.
      Assessment of autonomic tone was based on 5-min ECG and blood pressure recordings
      using time and frequency domains of heart rate variability (HRV) and a sequence
      method to derive baroreflex sensitivity (BRS). RESULTS: On admission,
      decompensated CHF patients had reduced HRV indices (p < 0.05) and depressed BRS
      (p < 0.01) as compared to those with stable CHF. After clinical stabilization (4
      +/- 2 days of treatment) time domain HRV indices and BRS increased (SDNN, 34.4 +/
      5.4 vs. 55.8 +/- 9.8 ms; RMSSD, 38.4 +/- 12.0 vs. 51.1 +/- 10.4 ms; BRS, 4.3 +/-
      0.7 vs. 7.6 +/- 1.3 ms/mmHg; all p < 0.01) and became similar to those seen in
      stable CHF patients. Breathing with oxygen affected autonomic indices neither in
      decompensated nor in stable CHF patients. Eight patients developed an episode of
      additional CHF worsening during hospitalization, in whom the third assessment was
      performed on discharge. Worsening in clinical status was followed by a decrease
      in HRV and BRS that became similar to those noted on admission. INTERPRETATION:
      HRV measures and BRS are severely deranged in the acute phase of CHF
      decompensation. Clinical stabilization results in an improvement of autonomic
      indices. However, subsequent clinical worsening adversely affects HRV and BRS.

PMID- 21080026
TI  - Chromosomal organization at the level of gene complexes.
AB  - Metazoan genomes primarily consist of non-coding DNA in comparison to coding
      regions. Non-coding fraction of the genome contains cis-regulatory elements,
      which ensure that the genetic code is read properly at the right time and space
      during development. Regulatory elements and their target genes define functional
      landscapes within the genome, and some developmentally important genes evolve by
      keeping the genes involved in specification of common organs/tissues in clusters
      and are termed gene complex. The clustering of genes involved in a common
      function may help in robust spatio-temporal gene expression. Gene complexes are
      often found to be evolutionarily conserved, and the classic example is the hox
      complex. The evolutionary constraints seen among gene complexes provide an ideal
      model system to understand cis and trans-regulation of gene function. This review
      will discuss the various characteristics of gene regulatory modules found within
      gene complexes and how they can be characterized.

PMID- 21080027
TI  - Emerging topics and new perspectives on HLA-G.
AB  - Following the Fifth International Conference on non-classical HLA-G antigens (HLA
      G), held in Paris in July 2009, we selected some topics which focus on emerging
      aspects in the setting of HLA-G functions. In particular, HLA-G molecules could
      play a role in: (1) various inflammatory disorders, such as multiple sclerosis,
      intracerebral hemorrhage, gastrointestinal, skin and rheumatic diseases, and
      asthma, where they may act as immunoregulatory factors; (2) the mechanisms to
      escape immune surveillance utilized by several viruses, such as human
      cytomegalovirus, herpes simplex virus type 1, rabies virus, hepatitis C virus,
      influenza virus type A and human immunodeficiency virus 1 (HIV-1); and (3)
      cytokine/chemokine network and stem cell transplantation, since they seem to
      modulate cell migration by the downregulation of chemokine receptor expression
      and mesenchymal stem cell activity blocking of effector cell functions and the
      generation of regulatory T cells. However, the immunomodulatory circuits mediated
      by HLA-G proteins still remain to be clarified.

PMID- 21080029
TI  - Biology of FGFRL1, the fifth fibroblast growth factor receptor.
AB  - FGFRL1 (fibroblast growth factor receptor like 1) is the most recently discovered
      member of the FGFR family. It contains three extracellular Ig-like domains
      similar to the classical FGFRs, but it lacks the protein tyrosine kinase domain
      and instead contains a short intracellular tail with a peculiar histidine-rich
      motif. The gene for FGFRL1 is found in all metazoans from sea anemone to mammals.
      FGFRL1 binds to FGF ligands and heparin with high affinity. It exerts a negative
      effect on cell proliferation, but a positive effect on cell differentiation. Mice
      with a targeted deletion of the Fgfrl1 gene die perinatally due to alterations in
      their diaphragm. These mice also show bilateral kidney agenesis, suggesting an
      essential role for Fgfrl1 in kidney development. A human patient with a
      frameshift mutation exhibits craniosynostosis, arguing for an additional role of
      FGFRL1 during bone formation. FGFRL1 contributes to the complexity of the FGF
      signaling system.

PMID- 21080030
TI  - Category learning in the context of co-presented items.
AB  - A series of four studies explore how the presentation of multiple items on each
      trial of a categorization task affects the course of category learning. In a
      three-category supervised classification task involving multi-dimensionally
      varying artificial organism-like stimuli, learners are shown a target plus two
      context items on every trial, with the context items' category membership
      explicitly identified. These triads vary in whether one, two, or all three
      categories are represented. This presentation context can support within-category
      comparison and/or between-category contrast. The most successful learning occurs
      when all categories are represented in each trial. This pattern occurs across two
      different underlying category structures and across variations in learners' prior
      knowledge of the relationship between the target and context items. These results
      appear to contrast with some other recent findings and make clear the potential
      importance of context-based inter-item evaluation in human category learning,
      which has implications for psychological theory and for real-world learning
      environments.

PMID- 21080028
TI  - The importance of HLA-G expression in embryos, trophoblast cells, and embryonic
      stem cells.
AB  - The nonclassical HLA-G molecule is a trophoblast-specific molecule present in
      almost every pregnancy. It differs from classical HLA class I molecules by the
      low degree of allelic variants and the high diversity of protein structures. HLA
      G is reported to be a tolerogenic molecule that acts on cells of both innate and
      adaptive immunity. At the maternal-fetal interface HLA-G seems to be responsible
      largely for the reprogramming of local maternal immune response. This review will
      focus on the HLA-G gene expression profile in pregnancy, in preimplantation
      embryos, and in human embryonic stem cells with emphasis on the structural
      diversity of the HLA-G protein and its potential functional and diagnostic
      implications.

PMID- 21080031
TI  - High fibrinogen level is an independent predictor of presence and extent of
      coronary artery disease among Italian population.
AB  - Few reports have so far investigated the relationship between fibrinogen levels
      and the extent of coronary artery disease (CAD) as evaluated by coronary
      angiography, that is therefore the aim of the current study. We measured
      fibrinogen in 2,121 consecutive patients undergoing coronary angiography.
      Patients were divided in 5 groups based on quintiles of fibrinogen levels.
      Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We
      additionally measured carotid intima-media thickness (CIMT) in a subgroup of 359
      patients. Patients with elevated fibrinogen were older (P = 0.038), with larger
      prevalence of diabetes (P = 0.027), female gender (P < 0.0001), hypertension (P <
      0.001), chronic renal failure (P < 0.0001), previous CVA (P = 0.036), less often
      with family history of CAD (P = 0.019) and previous PCI (P < 0.0001), more often
      presenting with ACS (P < 0.0001), more often on nitrates (P < 0.0001),
      clopidogrel (P = 0.009) and diuretics (P < 0.0001). Fibrinogen levels were
      linearly associated with baseline glycaemia (P < 0.017), WBC count (P < 0.0001),
      creatinine (P < 0.0001), and Platelet count (P < 0.0001) but inversely associated
      with RBC count (P < 0.0001). Fibrinogen levels were associated with CAD (P =
      0.001), especially for extremely high levels (5th percentile, P < 0.0001). At
      multivariate analysis, after correction for baseline confounding factors, high
      fibrinogen level (5th percentile) was still associated with the prevalence of CAD
      (P = 0.034). Furthermore, fibrinogen levels were related with maximal CIMT (r =
      0.12; P = 0.01), with larger prevalence of carotid plaques in patients with
      higher fibrinogen levels (5th quintile) as compared to remaining patients (P =
      0.046). This study showed that high fibrinogen level is significantly associated
      with CAD and carotid atherosclerosis.

PMID- 21080032
TI  - TonB-dependent outer-membrane proteins and siderophore utilization in Pseudomonas
      fluorescens Pf-5.
AB  - The soil bacterium Pseudomonas fluorescens Pf-5 produces two siderophores, a
      pyoverdine and enantio-pyochelin, and its proteome includes 45 TonB-dependent
      outer-membrane proteins, which commonly function in uptake of siderophores and
      other substrates from the environment. The 45 proteins share the conserved beta
      barrel and plug domains of TonB-dependent proteins but only 18 of them have an N
      terminal signaling domain characteristic of TonB-dependent transducers (TBDTs),
      which participate in cell-surface signaling systems. Phylogenetic analyses of the
      18 TBDTs and 27 TonB-dependent receptors (TBDRs), which lack the N-terminal
      signaling domain, suggest a complex evolutionary history including horizontal
      transfer among different microbial lineages. Putative functions were assigned to
      certain TBDRs and TBDTs in clades including well-characterized orthologs from
      other Pseudomonas spp. A mutant of Pf-5 with deletions in pyoverdine and enantio
      pyochelin biosynthesis genes was constructed and characterized for iron-limited
      growth and utilization of a spectrum of siderophores. The mutant could utilize as
      iron sources a large number of pyoverdines with diverse structures as well as
      ferric citrate, heme, and the siderophores ferrichrome, ferrioxamine B,
      enterobactin, and aerobactin. The diversity and complexity of the TBDTs and TBDRs
      with roles in iron uptake clearly indicate the importance of iron in the fitness
      and survival of Pf-5 in the environment.

PMID- 21080033
TI  - Genotypic and phenotypic characterization of genetic differentiation and
      diversity in the USDA rice mini-core collection.
AB  - A rice mini-core collection consisting of 217 accessions has been developed to
      represent the USDA core and whole collections that include 1,794 and 18,709
      accessions, respectively. To improve the efficiency of mining valuable genes and
      broadening the genetic diversity in breeding, genetic structure and diversity
      were analyzed using both genotypic (128 molecular markers) and phenotypic (14
      numerical traits) data. This mini-core had 13.5 alleles per locus, which is the
      most among the reported germplasm collections of rice. Similarly, polymorphic
      information content (PIC) value was 0.71 in the mini-core which is the highest
      with one exception. The high genetic diversity in the mini-core suggests there is
      a good possibility of mining genes of interest and selecting parents which will
      improve food production and quality. A model-based clustering analysis resulted
      in lowland rice including three groups, aus (39 accessions), indica (71) and
      their admixtures (5), upland rice including temperate japonica (32), tropical
      japonica (40), aromatic (6) and their admixtures (12) and wild rice (12)
      including glaberrima and four other species of Oryza. Group differentiation was
      analyzed using both genotypic distance Fst from 128 molecular markers and
      phenotypic (Mahalanobis) distance D(2) from 14 traits. Both dendrograms built by
      Fst and D(2) reached similar-differentiative relationship among these genetic
      groups, and the correlation coefficient showed high value 0.85 between Fst matrix
      and D(2) matrix. The information of genetic and phenotypic differentiation could
      be helpful for the association mapping of genes of interest. Analysis of
      genotypic and phenotypic diversity based on genetic structure would facilitate
      parent selection for broadening genetic base of modern rice cultivars via
      breeding effort.

PMID- 21080034
TI  - Proteomic analysis of cisplatin resistance in human ovarian cancer using 2-DE
      method.
AB  - Platinum-based chemotherapy, such as cisplatin, is the primary treatment for
      human ovarian cancer. However, overcoming drug resistance has become an important
      issue in cancer chemotherapy. In this study, we performed 2-DE and ESI-Q-TOF
      MS/MS analysis to identify differential proteins expression between cisplatin
      sensitive (A2780S) and cisplatin-resistant (A2780-CP) ovarian cancer cell lines.
      Of the 14 spots identified as differentially expressed (+/-over twofold, P <
      0.05) between the two cell lines, ten spots (corresponding to ten unique
      proteins) were positively identified by ESI-Q-TOF MS/MS analysis. These proteins
      include capsid glycoprotein, fructose-bisphosphate aldolase C, heterogeneous
      nuclear ribonucleoproteins A2/B1, putative RNA-binding protein 3, Ran-specific
      GTPase-activating protein, ubiquitin carboxyl-terminal hydrolase isozyme L1,
      stathmin, ATPSH protein, chromobox protein homolog3 and phosphoglycerate kinase
      1. The proteins identified in this study would be useful in revealing the
      mechanisms underlying cisplatin resistance and also provide some clues for
      further research.

PMID- 21080035
TI  - Interaction of prothrombin with a phospholipid surface: evidence for a membrane
      induced conformational change.
AB  - Prothrombin interacts with phosphatidylserine containing platelet membranes via
      its N-terminal, gamma-carboxyglutamate (gla) residue-rich domain. Once bound it
      is cleaved to form the active protease, thrombin (factor IIa). Human prothrombin
      was cleaved with cathepsin G in the absence of calcium and magnesium ions. Under
      these conditions, the gla domain was removed. Phospholipid protected the protein
      from this proteolytic event, and this suggests that a conformational change may
      be induced by interaction with phospholipids. Binding of prothrombin to a surface
      containing 20% phosphatidylserine/80% phosphatidylcholine was detected by surface
      plasmon resonance, whereas no interaction with gla-domainless prothrombin was
      observed. Binding of intact prothrombin in the presence of calcium ions showed
      complex association kinetics, suggesting multiple modes of initial interaction
      with the surface. The kinetics of the dissociation phase could be fitted to a two
      phase, exponential decay. This implies that there are at least two forms of the
      protein on the surface one of which dissociates tenfold more slowly than the
      other. Taken together, these data suggest that, on binding to a membrane surface,
      prothrombin undergoes a conformational change to a form which binds more tightly
      to the membrane.

PMID- 21080036
TI  - The effect of acute dose charge particle radiation on expression of DNA repair
      genes in mice.
AB  - The space radiation environment consists of trapped particle radiation, solar
      particle radiation, and galactic cosmic radiation (GCR), in which protons are the
      most abundant particle type. During missions to the moon or to Mars, the constant
      exposure to GCR and occasional exposure to particles emitted from solar particle
      events (SPE) are major health concerns for astronauts. Therefore, in order to
      determine health risks during space missions, an understanding of cellular
      responses to proton exposure is of primary importance. The expression of DNA
      repair genes in response to ionizing radiation (X-rays and gamma rays) has been
      studied, but data on DNA repair in response to protons is lacking. Using qPCR
      analysis, we investigated changes in gene expression induced by positively
      charged particles (protons) in four categories (0, 0.1, 1.0, and 2.0 Gy) in nine
      different DNA repair genes isolated from the testes of irradiated mice. DNA
      repair genes were selected on the basis of their known functions. These genes
      include ERCC1 (5' incision subunit, DNA strand break repair), ERCC2/NER (opening
      DNA around the damage, Nucleotide Excision Repair), XRCC1 (5' incision subunit,
      DNA strand break repair), XRCC3 (DNA break and cross-link repair), XPA (binds
      damaged DNA in preincision complex), XPC (damage recognition), ATA or ATM
      (activates checkpoint signaling upon double strand breaks), MLH1 (post
      replicative DNA mismatch repair), and PARP1 (base excision repair). Our results
      demonstrate that ERCC1, PARP1, and XPA genes showed no change at 0.1 Gy
      radiation, up-regulation at 1.0 Gy radiation (1.09 fold, 7.32 fold, 0.75 fold,
      respectively), and a remarkable increase in gene expression at 2.0 Gy radiation
      (4.83 fold, 57.58 fold and 87.58 fold, respectively). Expression of other genes,
      including ATM and XRCC3, was unchanged at 0.1 and 1.0 Gy radiation but showed up
      regulation at 2.0 Gy radiation (2.64 fold and 2.86 fold, respectively). We were
      unable to detect gene expression for the remaining four genes (XPC, ERCC2, XRCC1,
      and MLH1) in either the experimental or control animals.

PMID- 21080037
TI  - FoxO1 regulates muscle fiber-type specification and inhibits calcineurin
      signaling during C2C12 myoblast differentiation.
AB  - Adult skeletal muscle fibers can be categorized into slow-oxidative and fast
      glycolytic subtypes based on specialized metabolic and contractile properties.
      The Forkhead box O1 (FoxO1) transcription factor governs muscle growth,
      metabolism, and cell differentiation, and has been shown to be involved in
      regulating muscle fiber type specification. However, to date, the mechanism
      behind FoxO1-mediated fiber type diversity is still unclear. In this article,
      FoxO1 being expressed preferentially in fast twitch fiber enriched muscles is
      reported. Moreover, the autors also detected that FoxO1 expression decreased in
      both fast and slow muscles from mice undergoing endurance exercise which induced
      a fast-to-slow fiber type transition. Using C2C12 myoblast, constitutively active
      FoxO1 mutant altered the proportion of muscle fiber type composition toward a
      fast-glycolytic phenotype and attenuated calcineurin phosphatase activity. In
      addition, a transcriptionally inactive FoxO1 by resveratrol triggered the
      expression of genes related to slow-oxidative muscle but not sufficient to induce
      a complete slow fiber transformation. Taken together, these results suggest that
      FoxO1 up-regulates fast fiber-type formation and down-regulates muscle oxidative
      capacity at least in part through inhibition of the calcineurin pathway.

PMID- 21080038
TI  - The precursor to the germ cell-specific PCSK4 proteinase is inefficiently
      activated in transfected somatic cells: evidence of interaction with the BiP
      chaperone.
AB  - Proprotein convertase subtilisin/kexin type 4 (PCSK4), also known as proprotein
      convertase 4 (PC4), is a serine endoproteinase primarily expressed in testicular
      germ cells and in sperm. Inactivation of its gene in mouse causes male
      infertility. From studies of the biosynthesis of PCSK3/furin, its closest
      relative, it has been inferred that PCSK4 is synthesised in the endoplasmic
      reticulum as a zymogen; that it is rapidly matured by autocatalytic cleavage
      between the prodomain and the catalytic domain; that the cleaved prodomain
      remains attached to the mature enzyme; and that the enzyme is finally activated
      by the removal of the prodomain peptides following a secondary cleavage within
      the prodomain. In this study, we used human embryonic kidney 293 (HEK293) cells
      to study the biosynthesis of rat or human PCSK4. Our results show that the bulk
      of PCSK4 remains as an intracellular zymogen, presumably trapped in the
      endoplasmic reticulum, where it interacts with the general molecular chaperone
      glucose-regulated protein 78/Immunoglobulin heavy-chain binding protein
      (GRP78/BiP). These data suggest that, unlike other members of the convertase
      family, proPCSK4 cannot efficiently self-activate in somatic cells. These cells
      may lack the intracellular environment and the interacting molecules specific to
      testicular germ cells where this enzyme is normally expressed.

PMID- 21080039
TI  - The instinctual nation-state: non-Darwinian theories, state science and ultra
      nationalism in Oka Asajiro's Evolution and Human Life.
AB  - In his anthology of socio-political essays, Evolution and Human Life, Oka Asajiro
      (1868-1944), early twentieth century Japan's foremost advocate of evolutionism,
      developed a biological vision of the nation-state as super-organism that
      reflected the concerns and aims of German-inspired Meiji statism and anticipated
      aspects of radical ultra-nationalism. Drawing on non-Darwinian doctrines, Oka
      attempted to realize such a fused or organic state by enhancing social instincts
      that would bind the minzoku (ethnic nation) and state into a single living
      entity. Though mobilization during the Russo-Japanese War seemed to evince this
      super-organism, the increasingly contentious and complex society that emerged in
      the war's aftermath caused Oka to turn first to Lamarckism and eventually to
      orthogenesis in the hopes of preserving the instincts needed for a viable nation
      state. It is especially in the state interventionist measures that Oka finally
      came to endorse in order to forestall orthogenetically-driven degeneration that
      the technocratic proclivities of his statist orientation become most apparent.
      The article concludes by suggesting that Oka's emphasis on degeneration, autarkic
      expansion, and, most especially, totalitarian submersion of individuals into the
      statist collectivity indicates a complex relationship between his evolutionism
      and fascist ideology, what recent scholarship has dubbed radical Shinto ultra
      nationalism.

PMID- 21080040
TI  - The 'division of physiological labour': the birth, life and death of a concept.
AB  - The notion of the 'division of physiological labour' is today an outdated relic
      in the history of science. This contrasts with the fate of another notion, which
      was so frequently paired with the division of physiological labour, which is the
      concept of 'morphological differentiation.' This is one of the elementary modal
      concepts of ontogenesis. In this paper, we intend to target the problems and
      causes that gradually led biologists to combine these two notions during the 19th
      century, and to progressively dissociate them, retaining only the concept of
      differentiation by the early 20th century. We shall adhere to the following: 1.
      The primitive economic concept of the division of labour is not a descriptive
      notion denoting a type of organisation of labour, but an etiological one: the
      idea of a causal relationship between this type of organization and the
      improvement of the whole. 2. This concept rapidly interested naturalists such as
      Henri Milne-Edwards, who were keen to find a rational ground for hierarchizing
      living forms based on anatomical complexity. 3. The validation of this notion in
      the realms of biology was subject to at least two conditions which were far from
      being fully satisfied. This did not prevent, however, the initial success of the
      concept of the division of physiological labour during the second half of the
      19th century. 4. Finally, the gradual disqualification, within the Darwinian
      theoretical context, of the conception of an intrinsic hierarchical rank of
      organisms, led to a lack of interest in the concept of the physiological division
      of labour, at least in its non-Darwinian and non-ecological variant (the link
      between the division of labour within an organism and organic perfection).

PMID- 21080041
TI  - Youth perspectives on street outreach workers: results from a community-based
      survey.
AB  - The United Teen Equality Center in Lowell, Massachusetts uses Street Outreach
      Workers (SWs) to intervene with individuals 13-23 years old who are involved in
      high risk behaviors or in need of assistance. Few studies have explored the
      perceptions of SWs by their target population (both individuals they have worked
      with and those who they have not yet worked with). To better understand how youth
      perceive the SWs and to contribute to the scant literature regarding their roles
      and impacts, we conducted a community-based survey to capture youth perspectives
      of, and experiences with SWs. Regardless of whether they had worked with a SW,
      youth respondents reported that their peers believed the SWs made Lowell a better
      place. Youth who had prior contact with a SW were more likely to respond that
      their peers view the SWs as helpful to youth and respected. Youth who had no
      prior contact with SWs were more likely to report that SWs were not present where
      they lived. Among youth who had worked with a SW 38% received help finding a job
      and 67% indicated that working with a SW made a difference in their lives.
      Approximately 82% of individuals who participated in mediation activities led by
      the SWs reported that it resolved their conflict. These results support the value
      of SWs in helping youth meet their needs and in mediating disputes. SWs should
      continue to connect with local agencies to address the needs of youth, especially
      employment, which was a priority.

PMID- 21080042
TI  - Impact of socioeconomic status and sociodemographic factors on melanoma
      presentation among ethnic minorities.
AB  - Minority melanoma patients have worse survival. In this study, we evaluated the
      impact of socioeconomic and demographic factors on minority melanoma patients
      presenting to two different New York City hospitals (one public and one private)
      managed by the same multidisciplinary team. Sociodemographic and
      clinicopathologic characteristics were retrieved for melanoma patients presenting
      to Bellevue Hospital Center (BHC), a public hospital, and the New York University
      Cancer Institute (NYUCI), a private cancer center. Socioeconomic data was
      obtained from the United States Census Bureau database. The Kruskal-Wallis and
      chi-square tests were used to evaluate the associations between race/ethnicity
      and continuous and categorical variables (e.g. income, stage at presentation),
      respectively. Minorities comprised 2% (27/1296) of melanoma patients at the NYUCI
      compared to 42% (50/119) at BHC. Those presenting to the NYUCI were more likely
      to have a higher median household income (P = 0.05), a higher educational level
      (P = 0.04), and an earlier stage at presentation (P = 0.02) than those at BHC.
      NYUCI patients were predominantly covered by commercial insurance (70%), whereas
      Medicaid (62%) was common among BHC patients. Only 19% of Hispanic patients at
      BHC chose English as their preferred language. Our data demonstrate that language
      and health care system factors affect melanoma presentation in minorities.

PMID- 21080043
TI  - Diet, physical activity, and cardiovascular disease risk factors among older
      Chinese Americans living in New York City.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the US and affects
      Chinese Americans disproportionately compared to other ethnic groups in the
      American population. However, few studies have examined CVD risk factors,
      including diet and physical activity, in Chinese Americans. This investigation
      used a cross-sectional design to evaluate the dietary intake, dietary supplement
      use, and physical activity of 125 older Chinese Americans aged 50-98 years, and
      to determine how these behaviors may be related to obesity and other CVD risk
      factors. Sociodemographic information, CVD risk factors, dietary intake, and
      physical activity were obtained from all participants recruited from health fairs
      conducted in New York City (NYC). The findings revealed that older Chinese
      American adults living in NYC had a high prevalence of overweight and obesity,
      borderline hypertension, pre-diabetes, and diabetes. Many participants did not
      meet their daily requirements calcium, potassium, folate, vitamin B6, and vitamin
      B12, several minerals and vitamins important for cardiovascular health. Although
      most participants consumed an adequate numbers of servings of foods from the main
      food groups, most did not meet the recommended number of servings of dairy foods
      and only one in four adults took a multivitamin supplement daily. After adjusting
      for potential confounders, daily consumption of oil/sweets and dairy foods was
      positively associated with waist circumference. Also, daily consumption of
      oils/sweets, meats, and grains was positively associated with systolic blood
      pressure. The majority of the participants reported at least 30 min of moderate
      intensity physical activity per day. Dietary intake or supplement use did not
      show protective effects but performing vigorous physical activity may reduce risk
      of CVD in this population.

PMID- 21080044
TI  - Cloning, expression, purification, and characterization of cold-adapted alpha
      amylase from Pseudoalteromonas arctica GS230.
AB  - A cold-adapted alpha-amylase (ParAmy) gene from Pseudoalteromonas arctica GS230
      was cloned, sequenced, and expressed as an N-terminus His-tag fusion protein in
      E. coli. A recombinant protein was produced and purified with DEAE-sepherose ion
      exchange chromatography and Ni affinity chromatography. The molecular weight of
      ParAmy was estimated to be 55 KDa with sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). With an optimum temperature for activity 30  degrees
      C, ParAmy showed 34.5% of maximum activity at 0  degrees C and its activity
      decreased sharply at above 40  degrees C. ParAmy was stable in the range of pH 7
      8.5 at 30  degrees C for 1 h. ParAmy was activated by Mn(2+), K(+) and Na(+), and
      inhibited by Hg(2+), Cu(2+), and Fe(3+). N-Bromosuccinimid showed a significant
      repressive effect on enzyme activity. The K (m) and V (max) values of the alpha
      amylase for soluble starch were 7.28 mg/mL and 13.07 mg/mL min, respectively.
      This research suggests that Paramy has a good potential to be a cold-stable and
      alkalitolerant amylase in detergent industry.

PMID- 21080045
TI  - Risky lifestyle as a mediator of the relationship between deviant peer
      affiliation and dating violence victimization among adolescent girls.
AB  - Few studies have explored the possible contribution of the peer group to dating
      violence victimization. The current study tested the hypothesis that a risky
      lifestyle would mediate the relationship between deviant peer affiliation and
      dating violence victimization among adolescent girls. The proposed mediation
      model was derived from lifestyles and routine activities theories. A sample of
      550 girls (mean age = 15) drawn from a larger representative community sample in
      Quebec, Canada, completed a questionnaire on three forms of dating violence
      victimization (psychological, physical, and sexual). Results revealed that girls
      with a higher level of affiliation with deviant peers were more likely to endorse
      a risky lifestyle and reported higher rates of all forms of dating violence
      victimization. Further analyses showed that, while deviant peer affiliation is
      associated with dating violence victimization, this relationship may be
      explained, at least partially for psychological violence, and completely for
      physical/sexual violence, by the girls' own risky lifestyle. Future preventive
      interventions for adolescent dating violence victimization should target deviant
      peer groups, as well as adolescent girls who display a risky lifestyle.

PMID- 21080046
TI  - The concurrent and longitudinal effects of child disability types and health on
      family experiences.
AB  - This study examines the concurrent and longitudinal effects of children's
      disability types and health on family experiences, namely, parent divorce,
      mother's unemployment, and receipt of social welfare. The parent and school staff
      survey data for 1999 and 2004 from the Special Education Elementary Longitudinal
      Study were analyzed, when the ages of children with disabilities ranged from 6 to
      17. Weighted logistic regressions using Taylor Series Linearization were used to
      model the concurrent associations and longitudinal association between children's
      disability types and health and family experiences. Models were adjusted to
      account for other children in the family with disabilities, sociodemographic
      characteristics, and other family experiences variables. Family experiences
      varied significantly by disability type in 1999. Compared with families of
      children with learning disabilities, parents of children with emotional
      disturbances were 81% more likely to get divorced, and 2.5 times more likely to
      receive welfare from 1999 to 2004. Mothers of children with a secondary
      disability were 81% more likely to be unemployed than those of children without a
      secondary disability. These findings indicate that specific disability types in
      children have an influence on family experience, and that some of those
      influences may persist over time. Families of children with emotional
      disturbances appear to be particularly at risk for negative family experiences.
      Clinicians, educators, and policymakers should be aware of the complex needs of
      families of children with disabilities when considering the types of services and
      supports provided to both children with disabilities and their families.

PMID- 21080047
TI  - Anti-inflammation effects of Cordyceps sinensis mycelium in focal cerebral
      ischemic injury rats.
AB  - Brain ischemia-reperfusion (IR) triggers a complex series of biochemical events
      including inflammation. To test the neuroprotective efficacy of Cordyceps
      sinensis mycelium (CSM) in a rat model of focal cerebral IR, ischemic animals
      were treated with CSM. They were evaluated at 24 h after reperfusion for
      neurological deficit score. Furthermore, the mechanism of the anti-inflammatory
      potential of CSM in the regulation of nuclear factor kappaB, polymorphonuclear
      cells (PMN), interleukin-1beta (IL-1beta), inducible nitric oxide synthase
      (iNOS), tumor necrosis factor-alpha (TNF-alpha), adhesion molecule (ICAM-1), and
      cyclooxygenase-2 (COX-2) was determined by ELISA and immunohistochemistry. CSM
      significantly inhibited IR-induced up-regulation of NF-kappaB activation and the
      brain production of IL-1beta, TNF-alpha, iNOS, ICAM-1, and COX-2. Moreover, CSM
      suppressed infiltration of PMN. The study demonstrates the neuroprotective
      potential of CSM inhibition through anti-inflammation in a rat model of ischemia
      reperfusion.

PMID- 21080048
TI  - Sex and sexual orientation differences in personality in China.
AB  - Using data from an Internet survey, we assessed masculinity-femininity (self
      ascribed masculinity-femininity [Self-MF], gender-related interests,
      instrumentality, expressiveness) and Big Five personality traits in a Chinese
      sample of 201 heterosexual men, 220 homosexual men, 353 heterosexual women, and
      215 homosexual women. Sex differences and sexual orientation differences were
      largest for gender-related interests and Self-MF. Homosexual-heterosexual
      differences in emotional stability were opposite for men and women, supporting
      the "gender shift" over the "social stress" hypothesis. Sex and sexual
      orientation differences in gender-related interests, Self-MF, and emotional
      stability observed in China were consistent with those found in other countries,
      suggesting possible biological influences. In contrast, group differences in
      other traits were more variable, suggesting possible cultural influences.

PMID- 21080049
TI  - Judging pain and disability: effects of pain severity and physician specialty.
AB  - While considerable evidence indicates that the assessment of pain is an exercise
      in social cognition, provider contributions to pain assessment have received
      little attention. This study compared internist versus neurosurgeon ratings of
      pain and pain-related disability for hypothetical patients reporting either low
      or high levels of low back pain. Using practice characteristics as covariates, a
      multivariate analysis of covariance showed that both physician groups rated pain
      severity, but not measures of disability, as significantly lower for the low pain
      severity condition. Relative to internists, neurosurgeons rated both pain
      severity and pain-related disability as significantly lower, regardless of
      patient-reported pain severity. There were no interactions between physician
      specialty and patient-reported pain severity. Practice characteristics accounted
      for relatively little variance in ratings. Results are discussed in terms of
      differences in comparison levels for the physician groups, as well as
      implications for clinical practice and disability determination systems.

PMID- 21080050
TI  - The contribution of postmenopausal hormone use cessation to the declining
      incidence of breast cancer.
AB  - The striking decline in United States breast cancer incidence since 2002 has been
      widely attributed to a reduction in postmenopausal hormone use, yet very little
      analysis has been conducted to quantify the contribution of changes in hormone
      use to the declining trend. We used literature-based estimates of the relative
      risk and the changing prevalence of hormone use to estimate the impact of hormone
      use on the decline in breast cancer incidence between 2002 and 2003 among women
      aged 40-79. For the base case of a 44% decline in hormone use and a relative risk
      for current use of 1.5, we estimated that 43% of the decline in incidence was
      attributable to hormone use. By exploring a range of parameter values, we found
      that high, unlikely values of the relative risk (i.e., >= 2.25) and/or the
      percent decline in hormone use (i.e., >= 75%) would be required to account for
      100% of the observed decline in breast cancer incidence. We conclude that hormone
      use is unlikely to account for more than half of the observed decline in breast
      cancer incidence between 2002 and 2003. Further efforts are needed to quantify
      the potential contributions of other factors, such as the plateau in screening
      mammography utilization.

PMID- 21080051
TI  - Dietary patterns and breast cancer risk among Chinese women.
AB  - OBJECTIVE: The present study aimed to examine the relationship between dietary
      patterns and breast cancer risk among Chinese women. METHODS: Four hundred and
      thirty-eight cases with histologically confirmed primary breast cancer and 438
      controls were consecutively recruited. Cases were frequency matched to controls
      on 5-year age group and rural-urban residence. A validated food frequency
      questionnaire was used to assess dietary intake by face-to-face interviews.
      Dietary patterns were identified by factor analysis. Multivariate odds ratios
      (OR) and 95% confidence interval (CI) were estimated using unconditional logistic
      regression adjusted for various potential confounders. RESULTS: Two diet patterns
      were identified: vegetable-fruit-soy-milk-poultry-fish pattern and refined grain
      meat-pickle pattern. After adjustment for confounders, a 74% decreased risk was
      observed among women in the highest quartile of the vegetable-fruit-soy-milk
      poultry-fish dietary pattern relative to the lowest quartile (OR = 0.26, 95% CI =
      0.17-0.42). The refined grain-meat-pickle pattern was positively associated with
      breast cancer risk (OR = 2.58, 95% CI = 1.53, 4.34). Women with a high intake of
      the vegetable-fruit-soy-milk-poultry-fish pattern and a low intake of the refined
      grain-meat-pickle pattern showed a decreased risk of breast cancer (adjusted OR =
      0.26, 95% CI = 0.17-0.41). CONCLUSIONS: These results indicated that a diet
      characterized by a high consumption of vegetable/fruit/soy/milk/poultry/fish and
      a low consumption of refined grain/red meat/pickle is associated with a lower
      risk of breast cancer in Chinese women.

PMID- 21080052
TI  - Groundwater uranium and cancer incidence in South Carolina.
AB  - OBJECTIVE: This ecologic study tested the hypothesis that census tracts with
      elevated groundwater uranium and more frequent groundwater use have increased
      cancer incidence. METHODS: Data sources included: incident total, leukemia,
      prostate, breast, colorectal, lung, kidney, and bladder cancers (1996-2005, SC
      Central Cancer Registry); demographic and groundwater use (1990 US Census); and
      groundwater uranium concentrations (n = 4,600, from existing federal and state
      databases). Kriging was used to predict average uranium concentrations within
      tracts. The relationship between uranium and standardized cancer incidence ratios
      was modeled among tracts with substantial groundwater use via linear or
      semiparametric regression, with and without stratification by the proportion of
      African Americans in each area. RESULTS: A total of 134,685 cancer cases were
      evaluated. Tracts with >=50% groundwater use and uranium concentrations in the
      upper quartile had increased risks for colorectal, breast, kidney, prostate, and
      total cancer compared to referent tracts. Some of these relationships were more
      likely to be observed among tracts populated primarily by African Americans.
      CONCLUSION: SC regions with elevated groundwater uranium and more groundwater use
      may have an increased incidence of certain cancers, although additional research
      is needed since the design precluded adjustment for race or other predictive
      factors at the individual level.

PMID- 21080053
TI  - Maternal depressive symptoms and child social preference during the early school
      years: mediation by maternal warmth and child emotion regulation.
AB  - This longitudinal study examined processes that mediate the association between
      maternal depressive symptoms and peer social preference during the early school
      years. Three hundred and fifty six kindergarten children (182 boys) and their
      mothers participated in the study. During kindergarten, mothers reported their
      level of depressive symptomatology. In first grade, teachers rated children's
      emotion regulation at school and observers rated the affective quality of mother
      child interactions. During second grade, children's social preference was
      assessed by peer nomination. Results indicated that mothers' level of depressive
      symptomatology negatively predicted their child's social preference 2 years
      later, controlling for the family SES and teacher-rated social preference during
      kindergarten. Among European American families, the association between maternal
      depressive symptoms and social preference was partially mediated by maternal
      warmth and the child's emotion regulation. Although the relation between maternal
      depressive symptoms and children peer preference was stronger among African
      American families than Europrean American families, its mediation by the maternal
      warmth and child's emotion regulation was not found in African American families.

PMID- 21080054
TI  - Stable S/MAR-based episomal vectors are regulated at the chromatin level.
AB  - Episomal vectors assembled from defined genetic components are a promising
      alternative to traditional gene therapy vectors that integrate in the host genome
      and may cause insertional mutations. The vector pEPI-eGFP is stably retained in
      the episomal state in cultured mammalian cells at low copy number for many
      generations without integration into the host genome. Although pEPI-eGFP is a
      fully engineered vector, little is known about how it interacts with the host
      genome and about the molecular mechanisms that are responsible for its
      transcriptional activity. We have analyzed the expression of the episomal
      reporter gene eGFP under conditions that affect the chromatin state of the
      genome. We have also constructed pEPI derivatives carrying a tandem array of lac
      operator sequences, which allows in vivo visualization and manipulation of the
      chromatin state of the episome. We show that changes in chromatin state of both
      the host and pEPI-eGFP induces changes in episomal gene activity and influences
      the episome's nuclear distributions. We conclude that episomal genes are subject
      to control systems of the host, similarly to their counterparts in the host
      genome.

PMID- 21080055
TI  - Roles of myosin Va and Rab3D in membrane remodeling of immature secretory
      granules.
AB  - Neuroendocrine secretory granules (SGs) are formed at the trans-Golgi network
      (TGN) as immature intermediates. In PC12 cells, these immature SGs (ISGs) are
      transported within seconds to the cell cortex, where they move along actin
      filaments and complete maturation. This maturation process comprises
      acidification-dependent processing of cargo proteins, condensation of the SG
      matrix, and removal of membrane and proteins not destined to mature SGs (MSGs)
      into ISG-derived vesicles (IDVs). We investigated the roles of myosin Va and Rab3
      isoforms in the maturation of ISGs in neuroendocrine PC12 cells. The expression
      of dominant-negative mutants of myosin Va or Rab3D blocked the removal of the
      endoprotease furin from ISGs. Furthermore, expression of mutant Rab3D, but not of
      mutant myosin Va, impaired cargo processing of SGs. In conclusion, our data
      suggest an implication of myosin Va and Rab3D in the maturation of SGs where they
      participate in overlapping but not identical tasks.

PMID- 21080056
TI  - Chromogranin A and the tumor microenvironment.
AB  - Chromogranin A (CgA) is an acidic glycoprotein belonging to a family of regulated
      secretory proteins stored in the dense core granules of the adrenal medulla and
      of many other neuroendocrine cells and neurons. This protein is frequently used
      as a diagnostic and prognostic serum marker for a range of neuroendocrine tumors.
      Circulating CgA is also increased in patients with other diseases, including
      subpopulations of patients with non-neuroendocrine tumors, with important
      prognostic implications. A growing body of evidence suggests that CgA is more
      than a diagnostic/prognostic marker for cancer patients. Indeed, results of in
      vitro experiments and in vivo studies in animal models suggest that this protein
      and its fragments can affect several elements of the tumor microenvironment,
      including fibroblasts and endothelial cells. In this article, recent findings
      implicating CgA as a modulator of the tumor microenvironment and suggesting that
      abnormal secretion of CgA could play important roles in tumor progression and
      response to therapy in cancer patients are reviewed and discussed.

PMID- 21080058
TI  - Down-modulation of Ca2+ channels by endogenously released ATP and opioids: from
      the isolated chromaffin cell to the slice of adrenal medullae.
AB  - Modifications in Ca(2+) influx may lead to profound changes in the cell activity
      associated with Ca(2+)-dependent processes, from muscle contraction and
      neurotransmitter release to calcium-mediated cell death. Therefore, calcium entry
      into the cell requires fine regulation. In this context, understanding of the
      modulation of voltage-dependent Ca(2+) channels seems to be critical. The
      modulatory process results in the enhancement or decrement of calcium influx that
      may regulate the local and global cytosolic Ca(2+) concentrations. Here, we
      summarize the well-established data on this matter described in isolated
      chromaffin cells by our laboratory and others, and the new results we have
      obtained in a more physiological preparation: freshly isolated slices of mouse
      adrenal medullae.

PMID- 21080057
TI  - Lipid dynamics in exocytosis.
AB  - Regulated exocytosis of neurotransmitter- and hormone-containing vesicles
      underpins neuronal and hormonal communication and relies on a well-orchestrated
      series of molecular interactions. This in part involves the upstream formation of
      a complex of SNAREs and associated proteins leading to the eventual fusion of the
      vesicle membrane with the plasma membrane, a process that enables content
      release. Although the role of lipids in exocytosis is intuitive, it has long been
      overlooked at least compared to the extensive work on SNAREs. Here, we will
      present the latest advances in this rapidly developing field revealing that
      lipids actually play an active role in exocytosis by focusing on cholesterol, 3'
      phosphorylated phosphoinositides and phosphatidic acid.

PMID- 21080059
TI  - Modulation of calcium channels by taurine acting via a metabotropic-like glycine
      receptor.
AB  - Taurine is one of the most abundant free amino acids in the central nervous
      system, where it displays several functions. However, its molecular targets
      remain unknown. It is well known that taurine can activate GABA-A and strychnine
      sensitive glycine receptors, which increases a chloride conductance. In this
      study, we describe that acute application of taurine induces a dose-dependent
      inhibition of voltage-dependent calcium channels in chromaffin cells from bovine
      adrenal medullae. This taurine effect was not explained by the activation of
      either GABA-A, GABA-B or strychnine-sensitive glycine receptors. Interestingly,
      glycine mimicked the modulatory action exerted by taurine on calcium channels,
      although the acute application of glycine did not elicit any ionic current in
      these cells. Additionally, the modulation of calcium channels exerted by both
      taurine and glycine was prevented by the intracellular dialysis of GDP-beta-S.
      Thus, the modulation of voltage-dependent calcium channels by taurine seems to be
      mediated by a metabotropic-like glycinergic receptor coupled to G-protein
      activation in a membrane delimited pathway.

PMID- 21080060
TI  - Nanosecond electric pulses: a novel stimulus for triggering Ca2+ influx into
      chromaffin cells via voltage-gated Ca2+ channels.
AB  - Exposing bovine chromaffin cells to a single 5 ns, high-voltage (5 MV/m) electric
      pulse stimulates Ca(2+) entry into the cells via L-type voltage-gated Ca(2+)
      channels (VGCC), resulting in the release of catecholamine. In this study,
      fluorescence imaging was used to monitor nanosecond pulse-induced effects on
      intracellular Ca(2+) level ([Ca(2+)](i)) to investigate the contribution of other
      types of VGCCs expressed in these cells in mediating Ca(2+) entry. omega
      Conotoxin GVIA and omega-agatoxin IVA, antagonists of N-type and P/Q-type VGCCs,
      respectively, reduced the magnitude of the rise in [Ca(2+)](i) elicited by a 5 ns
      pulse. omega-conotoxin MVIIC, which blocks N- and P/Q-type VGCCs, had a similar
      effect. Blocking L-, N-, and P?Q-type channels simultaneously with a cocktail of
      VGCC inhibitors abolished the pulse-induced [Ca(2+)](i) response of the cells,
      suggesting Ca(2+) influx occurs only via VGCCs. Lowering extracellular K(+)
      concentration from 5 to 2 mM or pulsing cells in Na(+)-free medium suppressed the
      pulse-induced rise in [Ca(2+)](i) in the majority of cells. Thus, both membrane
      potential and Na(+) entry appear to play a role in the mechanism by which
      nanoelectropulses evoke Ca(2+) influx. However, activation of voltage-gated Na(+)
      channels (VGSC) is not involved since tetrodotoxin (TTX) failed to block the
      pulse-induced rise in [Ca(2+)](i). These findings demonstrate that a single
      electric pulse of only 5 ns duration serves as a novel stimulus to open multiple
      types of VGCCs in chromaffin cells in a manner involving Na(+) transport across
      the plasma membrane. Whether Na(+) transport occurs via non-selective cation
      channels and/or through lipid nanopores remains to be determined.

PMID- 21080061
TI  - Chromaffin progenitor cells from the adrenal medulla.
AB  - Chromaffin cells of the adrenal medulla are neural crest-derived cells of the
      sympathoadrenal lineage. Different lines of evidence suggest the existence of a
      subpopulation of proliferation-competent progenitor cells even in the adult
      state. The identification of sympathoadrenal progenitors in the adrenal would
      greatly enhance the understanding of adrenal physiology and their potential role
      in adrenal pathogenesis. Isolation and differentiation of these progenitor cells
      in culture would provide a tool to understand their development in vitro.
      Furthermore, due to the close relation to sympathetic neurons, these cells might
      provide an expandable source of cells for cell therapy in the treatment of
      neurodegenerative diseases. We therefore aim to establish protocols for the
      efficient isolation, enrichment and differentiation of chromaffin progenitor
      cells to dopaminergic neurons in culture.

PMID- 21080063
TI  - Multicentric breast cancer: clonality and prognostic studies.
AB  - Clonality of multicentric breast cancer has traditionally been difficult to
      assess. We aimed to assess this using analysis of TP53 status (expression and
      mutation status). These results were then incorporated into an analysis of
      prognostic factors in multicentric tumours in a 10-year follow up study. Clonal
      status of multicentric breast cancer foci (n = 88 foci) was determined by
      immunohistochemical and molecular studies of TP53 in a total of 40 patients.
      Prognostic factors from these patients were also compared with 80 age- and stage
      matched controls with unicentric breast cancer from the Royal Marsden NHS
      Foundation Trust Breast Cancer Database. Our results indicate that multicentric
      breast cancer foci were polyclonal within an individual patient in at least 10
      patients (25%) with respect to immunohistochemical staining and in four patients
      (10%) with respect to abnormal band shifts on single strand conformational
      polymorphism (SSCP) molecular analysis. No individual variable was predictive of
      multicentric or unicentric disease. However, there was a worse overall survival
      in the multicentric breast cancer patients in whom at least two cancer foci
      stained positively on TP53 immunohistochemistry compared with the matched control
      group (P = 0.04). In conclusion, these results suggest that a proportion of
      multicentric breast cancer foci are polyclonal with respect to TP53 status and
      that TP53 over-expression predicts for a poorer prognosis in multicentric breast
      cancer.

PMID- 21080062
TI  - Paracrine role of GABA in adrenal chromaffin cells.
AB  - The function of GABA in the adrenal medulla is still controversial. We will
      review experimental results in vivo and in vitro in adrenal chromaffin cells of
      various mammals to clarify what has been elucidated and what still remains to be
      settled.

PMID- 21080064
TI  - Defective GM3 synthesis in Cog2 null mutant CHO cells associates to
      mislocalization of lactosylceramide sialyltransferase in the Golgi complex.
AB  - The conserved oligomeric Golgi (COG) complex is a eight subunit (COG1 to 8)
      tethering complex involved in the retrograde trafficking of multiple Golgi
      processing proteins. Here we studied the glycolipid synthesis status in ldlC
      cells, a Cog2 null mutant CHO cell line. Biochemical studies revealed a block in
      the coupling between LacCer and GM3 synthesis, resulting in decreased levels of
      GM3 in these cells. Uncoupling was not attributable to decreased activity of the
      glycosyltransferase that uses LacCer as acceptor substrate (SialT1). Rather,
      immunocytochemical experiments evidenced a mislocalization of SialT1 as
      consequence of the lack of Cog2 in these cells. Co-immunoprecipitation
      experiments disclose a Cog2 mediated interaction of SialT1 with the COG complex
      member Cog1. Results indicate that cycling of some Golgi glycolipid
      glycosyltransferases depends on the participation of the COG complex and that
      deficiencies in COG complex subunits, by altering their traffic and localization,
      affect glycolipid composition.

PMID- 21080065
TI  - Changes in Na+, K+-ATPase activity and alpha 3 subunit expression in CNS after
      administration of Na+, K+-ATPase inhibitors.
AB  - The expression of Na(+), K(+)-ATPase alpha3 subunit and synaptosomal membrane
      Na(+), K(+)-ATPase activity were analyzed after administration of ouabain and
      endobain E, respectively commercial and endogenous Na(+), K(+)-ATPase inhibitors.
      Wistar rats received intracerebroventricularly ouabain or endobain E dissolved in
      saline solution or Tris-HCl, respectively or the vehicles (controls). Two days
      later, animals were decapitated, cerebral cortex and hippocampus removed and
      crude and synaptosomal membrane fractions were isolated. Western blot analysis
      showed that Na(+), K(+)-ATPase alpha3 subunit expression increased roughly 40%
      after administration of 10 or 100 nmoles ouabain in cerebral cortex but remained
      unaltered in hippocampus. After administration of 10 MUl endobain E (1 MUl = 28
      mg tissue) Na(+), K(+)-ATPase alpha3 subunit enhanced 130% in cerebral cortex and
      103% in hippocampus. The activity of Na(+), K(+)-ATPase in cortical synaptosomal
      membranes diminished or increased after administration of ouabain or endobain E,
      respectively. It is concluded that Na(+), K(+)-ATPase inhibitors modify
      differentially the expression of Na(+), K(+)-ATPase alpha3 subunit and enzyme
      activity, most likely involving compensatory mechanisms.

PMID- 21080066
TI  - Acute 17beta-estradiol pretreatment protects against abdominal aortic occlusion
      induced spinal cord ischemic-reperfusion injury.
AB  - Postoperative neurologic deficit due to spinal cord ischemia-reperfusion (I/R)
      injury is the most devastating complication following thoracoabdominal aortic
      aneurysm repairs. The protective potential for 17beta-Estradiol has not been yet
      studied in such injury. In this study, ischemia induction for 18 min in male New
      Zealand White rabbits resulted in the highest percentage (80%) of biphasic
      paraplegic outcome assessed by Tarlov's score. Acute Estradiol pretreatment (1
      mg/kg, i.p., 30 min before I/R induction) altered this outcome and significantly
      prevented the worsening pattern of neurologic deficits over 48 h of observation.
      Histopathologic and oxidative stress evaluations of lumbar spinal cords taken in
      delayed permanent paraplegic phase (48 h after ischemia induction), further
      confirmed protective efficacy of Estradiol in such context. In western blot
      analysis, the expression of cleaved caspase-3 and heat shock protein 70 declined
      in Estradiol pretreated group compared to ischemic control group. TUNEL assay
      also showed the efficacy of Estradiol to abate motor neuron apoptosis.
      Interestingly, Estradiol respectively increased and decreased the expression of
      Cyclooxygenase (COX)-1 and COX-2, to a significant extent. Estradiol, exerting
      its protection through affecting one or a combination of involved biochemical
      factors can constitute a potential candidate to protect against thoracoabdominal
      aortic aneurysm repairs induced spinal cord I/R injury.

PMID- 21080067
TI  - Phenylarsine oxide binding reveals redox-active and potential regulatory vicinal
      thiols on the catalytic subunit of protein phosphatase 2A.
AB  - Our earlier finding that the activity of protein phosphatase 2A from rat brain is
      inhibited by micromolar concentrations of the dithiol cross-linking reagent
      phenylarsine oxide (PAO) has encouraged the hypothesis that the catalytic subunit
      (PP2Ac) of PP2A contains one or more pairs of closely-spaced (vicinal) thiol
      pairs that may contribute to regulation of the enzyme. The results of the present
      study demonstrate using immobilized PAO-affinity chromatography that PP2Ac from
      rat brain formed stable DTT-sensitive adducts with PAO with or without associated
      regulatory subunits. In addition, a subset of the PAO-binding vicinal thiols of
      PP2Ac was readily oxidized to disulfide bonds in vitro. Importantly, a small
      fraction of PP2Ac was still found to contain disulfide bonds after applying
      stringent conditions designed to prevent protein disulfide bond formation during
      homogenization and fractionation of the brains. These findings establish the
      presence of potentially regulatory and redox-active PAO-binding vicinal thiols on
      the catalytic subunit of PP2A and suggest that a population of PP2Ac may contain
      disulfide bonds in vivo.

PMID- 21080069
TI  - Synthesis and properties of small interfering RNA duplexes carrying 5
      ethyluridine residues.
AB  - Oligoribonucleotides carrying 5-ethyluridine units were prepared using solid
      phase phosphoramidite chemistry. The introduction of the tert-butyldimethylsilyl
      group at the 2'-OH position proceeded in good yield and very high 2'
      regioselectivity. RNA duplexes carrying 5-ethyluridine either at the sense or the
      guide strands display RNAi activity comparable to or slightly better than that of
      unmodified RNA duplexes. Gene suppression experiments using luciferase targets in
      SH-SY5Y cells show that the ethyl group is generally well accepted at all
      positions although a small decrease in RNA interference activity is observed when
      one 5-ethylU residue is incorporated in the 3' overhangs.

PMID- 21080070
TI  - Design, synthesis and 3D-QSAR study of cytotoxic flavonoid derivatives.
AB  - Three series of flavonoid derivatives were designed and synthesized. All
      synthesized compounds were evaluated for cytotoxic activities against five human
      cancer cell lines, including K562, PC-3, MCF-7, A549, and HO8910. Among the
      compounds tested, compound 9 d exhibited the most potent cytotoxic activity with
      IC(50) values of 2.76-6.98 MUM. Further comparative molecular field analysis was
      performed to conduct a 3D quantitative structure-activity relationship study. The
      generated 3D-QSAR model could be used for further rational design of novel
      flavonoid analogs as highly potent cytotoxic agents.

PMID- 21080068
TI  - Cellular stress responses, mitostress and carnitine insufficiencies as critical
      determinants in aging and neurodegenerative disorders: role of hormesis and
      vitagenes.
AB  - The widely accepted oxidative stress theory of aging postulates that aging
      results from accumulation of oxidative damage. A prediction of this theory is
      that, among species, differential rates of aging may be apparent on the basis of
      intrinsic differences in oxidative damage accrual. Although widely accepted,
      there is a growing number of exceptions to this theory, most contingently related
      to genetic model organism investigations. Proteins are one of the prime targets
      for oxidative damage and cysteine residues are particularly sensitive to
      reversible and irreversible oxidation. The adaptation and survival of cells and
      organisms requires the ability to sense proteotoxic insults and to coordinate
      protective cellular stress response pathways and chaperone networks related to
      protein quality control and stability. The toxic effects that stem from the
      misassembly or aggregation of proteins or peptides, in any cell type, are
      collectively termed proteotoxicity. Despite the abundance and apparent capacity
      of chaperones and other components of homeostasis to restore folding equilibrium,
      the cell appears poorly adapted for chronic proteotoxic stress which increases in
      cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of
      cellular stress response pathways has emerging implications for the treatment of
      human diseases, including neurodegenerative disorders, cardiovascular disease,
      and cancer. A critical key to successful medical intervention is getting the dose
      right. Achieving this goal can be extremely challenging due to human inter
      individual variation as affected by age, gender, diet, exercise, genetic factors
      and health status. The nature of the dose response in and adjacent to the
      therapeutic zones, over the past decade has received considerable advances. The
      hormetic dose-response, challenging long-standing beliefs about the nature of the
      dose-response in a lowdose zone, has the potential to affect significantly the
      design of pre-clinical studies and clinical trials as well as strategies for
      optimal patient dosing in the treatment of numerous diseases. Given the broad
      cytoprotective properties of the heat shock response there is now strong interest
      in discovering and developing pharmacological agents capable of inducing stress
      responses, including carnitines. This paper describes in mechanistic detail how
      hormetic dose responses are mediated for endogenous cellular defense pathways,
      including the possible signaling mechanisms by which the carnitine system, by
      interplaying metabolism, mitochondrial energetics and activation of critical
      vitagenes, modulates signal transduction cascades that confer cytoprotection
      against chronic degenerative damage associated to aging and neurodegenerative
      disorders.

PMID- 21080072
TI  - Arrest of the true culprit and acquittal of the innocent? Genetic revelations
      charge APOL1 variants with kidney disease susceptibility.

PMID- 21080074
TI  - Assessment of the serial changes of vessel wall contents in atherosclerotic
      coronary lesion with bioresorbable everolimus-eluting vascular scaffolds using
      Shin's method: an IVUS study.
AB  - Although serial changes in necrotic core and calcium are regarded as surrogates
      for the bioresorption process in patients treated with the bioresorbable
      everolimus-eluting vascular scaffolds (BVS), these temporal changes have not yet
      been fully investigated. Shin's method may be offer a more suitable technique for
      this analysis because it includes all the contents of both the lumen and vessel
      wall. The purpose of this study was to assess the serial changes of necrotic core
      and dense calcium content in coronary lesions that were treated with a BVS
      implant using Virtual Histology intravascular ultrasound (VH-IVUS) analyzed using
      Shin's method. A total of 29 patients (92 coronary segments) were imaged to
      evaluate the serial changes in necrotic core and dense calcium using Shin's
      method. Lesions treated with a BVS implant were analyzed with serial VH-IVUS
      assessments, i.e., pre- and post-stenting, and at 6 months and 2 years follow-up.
      In Shin's method contours are drawn around the IVUS catheter (instead of
      delineating the lumen) and the vessel. The mean necrotic core area decreased by
      6.9% from post-stenting to 6 months (1.71 +/- 1.03 mm2 vs. 1.36 +/- 0.91 mm2, P =
      0.027), and by 20.5% (1.71 +/- 1.03 mm2 vs. 1.20 +/- 0.70 mm2, P = 0.003) from
      post-steting to 2 years; while the mean dense calcium areas decreased by 27.2%
      (1.07 +/- 0.55 mm2 vs. 0.78 +/- 0.64 mm2, P = 0.039) from post-stenting and 2
      years. At 2 years, absolute necrotic core and dense calcium content were
      significantly decreased as compared to post-stenting values. The present study
      demonstrates that the bioresorption process in patients who undergoing BVS device
      implantation can be assessed using VH-IVUS analysed using Shin's method.

PMID- 21080075
TI  - IgE-mediated cross-reactivity among leguminous seed proteins in peanut allergic
      children.
AB  - The immunological cross-reactivity among major protein- and oil-crops, including
      lupin, lentil, pea, peanut, kidney bean and soybean, has been studied by a
      combination of in vitro and in vivo experimental approaches: SDS-PAGE separations
      of legume protein extracts and immuno-blot revelations with 12 peanut-sensitive
      subjects' sera, Immuno-CAP and Skin Prick tests on the same subjects. The immuno
      blotting data showed a wide range of IgE-binding responses both displayed by one
      subject towards different plant extracts and among subjects. Differences were
      both quantitative and qualitative. The prevalent responses of most subjects' sera
      were seen with peanut polypeptides, as expected, as well as with various
      polypeptides of the other legumes, the most recurrent of which were the basic
      subunits of the 11S globulins. The distribution of in vivo responses generally
      paralleled those obtained by in vitro approaches with strong responses elicited
      by peanut, lentil and pea protein extracts, especially by most sensitive
      subjects, thus providing a consistent overall set of results. In this work, the
      comparison of various approaches has allowed us to get an overall broad picture
      of the immunological cross-reactivities among proteins of widely used different
      seed species and to hypothesize the role of most conserved specific polypeptides.

PMID- 21080076
TI  - Variations in bran carotenoid levels within and between rice subgroups.
AB  - Rice (Oryza sativa L.) is a major grain in the human diet and carotenoids are
      valuable antioxidants. However, little is known about varietal differences in the
      carotenoid contents of the rice bran. The objective of this study is to determine
      the relative differences in bran carotenoid levels among all the five subgroups
      of rice. Measurements were made by a recently described, rapid non-destructive
      fluorescence quenching method. Confirmation by high performance liquid
      chromatography (HPLC) after solvent extraction of the bran indicated that the
      major carotenoid was lutein. Our data showed that carotenoid levels were stable
      over 10 years of storage. Tropical japonica rice, the most consumed subgroup in
      the United States, tended to have the lowest levels of carotenoids in the bran
      while temperate japonicas had the highest. These differences in carotenoid
      content may open up new opportunities for identifying or breeding rice varieties
      with higher nutritional value.

PMID- 21080073
TI  - Toward understanding protocell mechanosensation.
AB  - Mechanosensitive (MS) channels can prevent bacterial bursting during hypo-osmotic
      shocks by responding to increases in lateral tension at the membrane level
      through an integrated and coordinated opening mechanism. Mechanical regulation in
      protocells could have been one of the first mechanisms to evolve in order to
      preserve their integrity against changing environmental conditions. How has the
      rich functional diversity found in present cells been created throughout
      evolution, and what did the primordial MS channels look like? This review has
      been written with the aim of identifying which factors may have been important
      for the appearance of the first osmotic valve in a prebiotic context, and what
      this valve may have been like. It highlights the mechanical properties of lipid
      bilayers, the association of peptides as aggregates in membranes, and the
      conservation of sequence motifs as central aspects to understand the evolution of
      proteins that gate below the tension required for spontaneous pore formation and
      membrane rupture. The arguments developed here apply to both MscL and MscS
      homologs, but could be valid to mechano-susceptible proteins in general.

PMID- 21080077
TI  - A novel human derived cell-penetrating peptide in drug delivery.
AB  - Cell-penetrating peptides can carry a variety of biologically active molecules
      into cells. Here we have identified a novel CPP derived from the C-terminus of
      human extracellular superoxide dismutase (hC-SOD3) which was shown to be located
      throughout in the cytoplasm and nucleus by fluorescence microscopy investigation.
      Furthermore, when apoptin fused to hC-SOD3, it was translocated efficiently into
      HeLa cells resulting in antitumor activities. This study shows that hC-SOD3 has
      the potential to penetrate and translocate cargo molecules into cells and has no
      cytotoxicity at effective concentration.

PMID- 21080078
TI  - Characterization of SSU5C promoter of a rbcS gene from duckweed (Lemna gibba).
AB  - Photosynthesis-associated nuclear genes are able to respond to multiple
      environmental and developmental signals. Studies have shown that light signals
      coordinate with hormone signaling pathways to control photomorphogenesis. A small
      subunit of ribulose-1,5 bisphosphate carboxylase/oxygenase (rbcS) gene promoter
      was cloned from duckweed (Lemna gibba). Sequence analysis revealed this promoter
      is different from the previously reported rbcs promoters and is named SSU5C.
      Analysis of T1 transgenic tobacco plants with a reporter gene under the control
      of the SSU5C promoter revealed that this promoter is tissue-specific and is
      positively regulated by red light. Promoter deletion analysis confirmed a region
      from position -152 to -49 relative to the start of transcription containing boxes
      X, Y and Z, and is identified to be critical for phytochrome responses. Further
      functional analysis of constructs of box-X, Y, Z, which was respectively fused to
      the basal SSU5C promoter, defined boxes X, Y and Z alone are able to direct
      phytochrome-regulated expression, indicating that boxes Y and Z are different
      from those of the SSU5B promoters in L. gibba. This promoter may be used for
      plant gene expression in a tissue-specific manner.

PMID- 21080079
TI  - Gene polymorphism of vascular endothelial growth factor -1154 G>A is associated
      with hypertensive nephropathy in a Hispanic population.
AB  - The aim of this study was to determine the association between hypertensive
      nephropathy and gene polymorphisms of vascular endothelial growth factor (VEGF)
      in a self-reported Hispanic patient group. A total of 155 Hispanic living kidney
      donors as controls and a total of 86 Hispanic kidney transplant patients, whose
      renal failure was attributed to hypertensive nephropathy after ruling out
      diabetes mellitus or other causes, were genotyped for four different single
      nucleotide polymorphisms of VEGF: -2578 C>A (rs699947), -1154 G>A (rs1570360), 
      460 C>T (rs833061), and +936 C>T (rs3025039). The homozygous mutant type (AA) of
      VEGF -1154 G>A (rs1570360) was found with significantly higher frequency in the
      hypertensive nephropathy patients than in controls. On the other hand, homozygous
      wild type (GG) was found less frequently in the hypertensive nephropathy patient
      group than in the control group. Linkage disequilibrium (LD) analyses revealed a
      high degree of LD among VEGF -2578 C>A (rs699947), VEGF -1154 G>A (rs1570360),
      and VEGF -460 C>T (rs833061). The haplotype analysis revealed that two
      haplotypes, CGTC and CATC (in the order of VEGF -2578 C>A (rs699947), -1154 G>A
      (1570360), -460 C>T (rs833061), and +936 C>T (3025039)), were significantly
      associated with hypertensive nephropathy in Hispanic patients. Hence, the -1154
      G>A polymorphism (rs1570360) and two haplotypes (CGTC and CATC) of VEGF appear to
      be associated with hypertensive nephropathy in Hispanic patients who developed
      end-stage renal disease requiring kidney transplant.

PMID- 21080080
TI  - Effect of ketamine administration on memory consolidation, p-CREB and c-fos
      expression in the hippocampal slices of minor rats.
AB  - To investigate the effect of ketamine administration on memory consolidation, p
      CREB and c-fos expression in hippocampus of infant rats and the possible
      mechanism. Ninety-six SD rats of 21 days old were divided into seven groups, Y
      maze was used to test the ability of learning and memory for minor rats. p-CREB
      and c-fos protein expression was tested by immunhistochemistry. The results
      showed that the memory consolidation rate in normal saline group mice was higher
      than that in k1a and k7a group (P<0.05). However, normal saline group between k1b
      and k7b group was not significant difference. The p-CREB and c-fos protein
      expressing cells of normal saline group were higher than those in passive control
      group, pseudotraining group, k1a and k7a group (P<0.05). However, there was not
      significant difference between normal saline group and k1b or k7b group. The c
      fos protein expressing cells of pseudotraining group was higher than those in
      passive control group, however, the p-CREB protein expressing cells was not
      significant difference. Therefore, administration of ketamine may temporally
      affect the ability of memory consolidation rate of minor rats through suppressing
      the expression of p-CREB and c-fos protein in hippocampus.

PMID- 21080081
TI  - Association of deep venous thrombosis with prothrombotic gene polymorphism
      identified in lung cancer cases.
AB  - Venous thrombosis is a significant cause of morbidity and mortality in patients
      with malignancies. We aimed to investigate the association between prothrombotic
      gene polymorphisms detected in lung cancer cases and deep venous thrombosis
      (DVT). Totally 66 patients with an established diagnosis of lung cancer, of which
      33 developed DVT, were enrolled. Multiplex PCR technique and reverse
      hybridization strip assay were performed on DNA extracted from peripheral blood,
      in order to analyze prothrombin G20210A, factor V G1691A,
      methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin
      converting enzyme (ACE), plasminogen activator inhibitor-1 (PAI-1), and
      glycoprotein IIIa (Gp IIIa) gene mutations. Among prothrombotic gene
      polymorphisms investigated in this study, the commonest ones were PAI-1 4G/5G
      (56% heterozygous, 39% homozygous) and ACE gene mutations (58% heterozygous, 17%
      homozygous). The presence of homozygous MTHFR A1298C mutation was significantly
      associated with DVT (P=0.020). Comparing the lung cancer patients with and
      without DVT, only MTHFR A1298C gene polymorphism differed significantly
      (P=0.040). We determined a higher rate of prothrombotic gene mutations in lung
      cancer patients who developed DVT. However, statistical significance was achieved
      only for MTHFR A1298C gene mutation. Therefore, nongenetic factors for
      disturbance of hemostatic metabolism should also be considered in lung cancer
      patients.

PMID- 21080082
TI  - Varied association of prothrombin G20210A polymorphism with coronary artery
      disease susceptibility in different ethnic groups: evidence from 15,041 cases and
      21,507 controls.
AB  - Published data on the association between prothrombin G20210A polymorphism and
      coronary artery disease (CAD) risk are inconclusive. To derive a more precise
      estimation of the relationship, a meta-analysis was performed. A total of 42 case
      control studies including 15,041 cases and 21,507 controls were included in this
      meta-analysis. Overall, significantly elevated CAD risk was associated with
      prothrombin G20210A polymorphism (OR, 1.22; 95% CI 1.07-1.40; P=0.003) when 39
      eligible studies were pooled into the meta-analysis. In the subgroup analysis,
      borderline statistically increased risk was found for myocardial infarction in 22
      case-control studies (OR, 1.27; 95% CI 1.00-1.61; P=0.05). When stratified by
      ethnicity, significantly elevated risk was found in Europeans (OR, 1.19; 95% CI,
      1.02-1.38; P=0.02). However, no statistical differences were found among
      Americans and Asians. In summary, this meta-analysis indicated that prothrombin
      G20210A allele is a low-penetrant risk factor for developing CAD in Europeans.

PMID- 21080083
TI  - Protection of CHO cells by transfer of survivin driven by ovarian-specific
      promoter OSP-2.
AB  - Chemotherapy is the major therapy for cancer in clinic. However, chemotherapeutic
      agents can harm the other tissues/organs besides cancer. Thus, there are great
      interests in protecting the innocents by the transfer of protective genes. There
      are two problems to be solved, one is the selection of protective genes and the
      other is the orientation of the exotic genes. Recent researches demonstrated that
      the principal mechanism of chemotherapeutics was through apoptosis. Hereby,
      introduction of anti-apoptosis genes might interrupt the processes of apoptosis
      to avoid side effect from chemotherapeutics. On the other hand, tissue-specific
      promoters, which control gene expression in a tissue-specific manner, might be an
      alternative tool to guarantee the location of target genes. In this research, we
      applied gene therapy to chemoprotection using anti-apoptosis gene survivin and
      ovarian-specific promoter OSP-2. The results showed that OSP-2 could specifically
      drive the expression of survivin in ovarian cells and survivin could protect
      cells via inhibiting apoptosis. This might put a light on the future of
      chemoprotective gene therapy.

PMID- 21080084
TI  - Prevalence of complementary/alternative medicines (CAMs) in a cancer population
      in northern Italy receiving antineoplastic treatments and relationship with
      quality of life and psychometric features.
AB  - PURPOSE: To explore the use of CAM (Complementary/Alternative Medicine) in a
      population of cancer patients undergoing antineoplastic therapy, and to compare
      differences in sociodemographics, quality of life, and psychological features
      between CAM users and non-users. METHODS: The study population was consecutive
      cancer patients undergoing antineoplastic treatment in three Piedmont cancer
      centers. Data were collected from anonymous questionnaires investigating CAM use
      or not, and what type if used, and sociodemographics, and through validated
      psychometric instruments to assess psychological features: Functional Assessment
      of Cancer Therapy-General, the Hospital Anxiety and Depression Scale, and the
      Mini Mental Adjustment to Cancer Scale. RESULTS: Of the 288 evaluable patients,
      52 (18.1%) reported using one or more types of CAM; the most often cited were
      herbs, special diets and body-based practices, such as plantar reflexology,
      chiropractic application, and massage. On quality of life assessment, CAM users
      scored lower than CAM non-users for physical wellbeing (P = 0.006); no
      significant differences emerged for anxiety and depression and coping styles.
      CONCLUSIONS: CAM use is less prevalent in northern Italy than in most other
      European countries. CAM users were found to have a lower quality of life than CAM
      non-users.

PMID- 21080085
TI  - MDM2 is overexpressed and regulated by the eukaryotic translation initiation
      factor 4E (eIF4E) in human squamous cell carcinoma of esophagus.
AB  - BACKGROUND: We investigated the association between the increased eukaryotic
      translation initiation factor 4E (eIF4E) level and MDM2 overexpression in the
      esophageal cancer tissue and cells. METHODS: This was a retrospective study of
      specimens from esophageal cancer patients treated over a 5-year period in a
      Taiwan university hospital. The predictor variable was eIF4E level in esophageal
      tumors and CE48T/VGH and TE6 esophageal carcinoma cell lines. The main outcome
      variable was MDM2 overexpression. Appropriate descriptive and univariate
      statistics were computed, and a P value of <0.05 was considered statistically
      significant. RESULTS: There were two study sample groups. Immunohistochemistry
      analyses of the first sample group (51 esophageal tumors) revealed that 19
      specimens demonstrated MDM2 elevation and 20 specimens had eIF4E overexpression.
      eIF4E elevation was evidenced by accumulation of the protein in the cytoplasm.
      There was a significant association between the eIF4E and MDM2 expression (P <
      0.001). Western blot analysis and semiquantitative reverse transcriptase
      polymerase chain reaction of the second specimen group (20 pairs of tumors and
      normal tissues) revealed the co-elevation of MDM2 and eIF4E (P = 0.008). There
      was no increased mdm2 transcript in most of the specimens. Without significant
      alterations in the mdm2 mRNA level and subcellular distribution, MDM2 protein was
      upregulated in CE48T/VGH cultured cells expressing ectopic eIF4E. Conversely,
      reduction of eIF4E by specific siRNA enabled TE6 cells synthesizing reduced
      amounts of MDM2. CONCLUSIONS: Our findings indicate that MDM2 protein levels are
      strongly associated with and regulated by eIF4E in a posttranscriptional
      mechanism in esophageal cancer.

PMID- 21080086
TI  - Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer
      using invisible near-infrared fluorescence light.
AB  - BACKGROUND: Sentinel lymph node (SLN) mapping in colorectal cancer may have
      prognostic and therapeutic significance; however, currently available techniques
      are not optimal. We hypothesized that the combination of invisible near-infrared
      (NIR) fluorescent light and ex vivo injection could solve remaining problems of
      SLN mapping in colorectal cancer. METHODS: The FLARE imaging system was used for
      real-time identification of SLNs after injection of the NIR lymphatic tracer
      HSA800 in the colon and rectum of (n = 4) pigs. A total of 32 SLN mappings were
      performed in vivo and ex vivo after oncologic resection using an identical
      injection technique. Guided by these results, SLN mappings were performed in ex
      vivo tissue specimens of 24 consecutive colorectal cancer patients undergoing
      resection. RESULTS: Lymph flow could be followed in real-time from the injection
      site to the SLN using NIR fluorescence. In pigs, the SLN was identified in 32 of
      32 (100%) of SLN mappings under both in vivo and ex vivo conditions. Clinically,
      SLNs were identified in all patients (n = 24) using the ex vivo strategy within 5
      min after injection of fluorescent tracer. Also, 9 patients showed lymph node
      involvement (N1 disease). In 1 patient, a 3-mm mesenteric metastasis was found
      adjacent to a tumor-negative SLN. CONCLUSIONS: The current pilot study shows
      proof of principle that ex vivo NIR fluorescence-guided SLN mapping can provide
      high-sensitivity, rapid, and accurate identification of SLNs in colon and rectum.
      This creates an experimental platform to test optimized, non-FDA-approved NIR
      fluorescent lymphatic tracers in a clinical setting.

PMID- 21080087
TI  - Inadequate margins of excision when undergoing mastectomy for breast cancer:
      which patients are at risk?
AB  - BACKGROUND: We analyzed the margin status and risk factors for inadequate margins
      among patients who underwent skin-sparing mastectomies (SSM) and traditional
      total mastectomies (TM). MATERIALS AND METHODS: Patients undergoing mastectomies
      from 2003 to 2009 were included. Margins of excision were considered positive if
      carcinoma was at an inked margin and were considered close if such disease was
      within 2 mm of an inked margin. RESULTS: A total of 426 patients were identified.
      The mean age was 60 years and 90% were white. Mean tumor size was 2.6 cm and 44%
      had multiple ipsilateral carcinomas. Of 426 patients, 177 (42%) underwent SSM
      with reconstruction and 249 (58%) TM. The rate of positive or close margins on
      the initial specimen was 29% for SSM vs. 12% for TM (P < 0.01), and the rate of
      reoperation for margins was 7% for SSM vs. 2% for TM (P < 0.01). Logistic
      regression analysis revealed that independent risk factors for initial close or
      positive margins included SSM (odds ratio 2.36, 95% confidence interval [95% CI]
      1.05-5.30), multiple ipsilateral tumors (OR 2.12, 95% CI 1.05-4.24), and upper
      inner quadrant location (OR 2.58, 95% CI 1.07-6.19). Mean follow-up time was 28
      months, and the local recurrence rate was 0.9%. Local recurrence rates were not
      different for those undergoing SSM (1.1%) vs. TM (0.8%, P = NS). CONCLUSIONS:
      Mastectomy patients undergoing SSM, with multiple ipsilateral tumors, and/or
      upper-inner quadrant disease are at significantly higher risk for inadequate
      margins of excision. These patients warrant more vigilant intraoperative
      attention to margin status to ensure adequate margins at the end of the first
      operation.

PMID- 21080088
TI  - Single-access transumbilical diagnostic laparoscopy for pancreatic tumor using
      curved and reusable instruments.
AB  - INTRODUCTION: Diagnostic laparoscopy in pancreatic tumors remains controversial.
      The main argument in favor of this procedure is that it helps prevent a delay of
      chemotherapy in cases of unresectable tumors or peritoneal/lymph node metastasis.
      We report a technique of performing this exploration through single-incision
      laparoscopy. VIDEO: The umbilicus is incised, and a purse-string suture is
      applied. An 11-mm nondisposable trocar is inserted for a 10-mm, 30 degrees 
      angled scope. Curved and reusable instruments (Karl Storz-Endoskope, Tuttlingen,
      Germany) are inserted transumbilically. Laparoscopic exploration of the cavity
      allows the visualization of suspected peritoneal or lymph node metastasis.
      Peritoneal lavage for cytology is performed. Biopsy is accomplished through the
      curved shape of the instruments, which establishes the working triangulation
      inside the abdomen as well as externally. Laparoscopic ultrasonography of the
      liver and of the pancreas (after opening the lesser sac) is performed after
      replacement of the 11-mm trocar with a 13-mm trocar and the use of a 5-mm scope.
      The procedure can be continued either by laparoscopy or by open surgery. At
      completion, the umbilicus is meticulously closed to avoid complications. RESULTS:
      Operative time is 45-60 minutes, blood loss is minimal, and the size of the
      umbilical incision is less than 15 mm. CONCLUSIONS: In case of unresectable
      tumors or peritoneal metastasis, single-access diagnostic laparoscopy for
      pancreatic tumors permits the start of chemotherapy after less than 7 days.
      Curved and reusable instruments allow the achievement of ergonomic conditions as
      classic laparoscopy, without increasing of conventional laparoscopic cost.

PMID- 21080089
TI  - Retropalatal Muller grade is associated with the severity of obstructive sleep
      apnea in non-obese Asian patients. Retropalatal Muller grade and OSA in non
      obese.
AB  - PURPOSE: The aim of this study was to investigate whether physical evaluations
      could be used for predicting the presence and severity of obstructive sleep apnea
      (OSA) in non-obese snoring patients. METHODS: This is a retrospective study, and
      a total of 244 non-obese (body mass index, BMI, <27 kg/m(2)) snoring patients
      (178 men and 66 women; mean age = 43.1 +/- 12.1 years) were included. Each
      patient underwent polysomnography and a thorough physical examination, including
      flexible nasopharyngoscopy and Muller maneuver. Patients were divided into four
      groups based on apnea-hypopnea index (AHI) scores: normal (simple snoring), AHI <
      5; mild OSA, 5 ? AHI < 15; moderate OSA, 15 ? AHI < 30; severe OSA, AHI ? 30.
      Logistic regression was used to identify risk factors for OSA severity. RESULTS:
      Fifty-nine patients (24%) were simple snorers. The prevalence of sleep apnea
      (mild, moderate, or severe OSA) for our non-obese snoring patients was 76%.
      Univariate logistic analyses showed that higher BMI, male gender and retropalatal
      Muller grades were significantly associated with OSA severity. Multivariate
      logistic regression analysis identified male gender and retropalatal Muller grade
      as risk factors for OSA in non-obese snoring patients. CONCLUSIONS: Physical
      examination may be useful for studying the upper airway in non-obese snoring
      patients. Flexible nasopharyngoscopy with Muller maneuver appears to be useful
      for evaluating the severity of OSA in non-obese patients. Retropalatal Muller
      grade is highly related to both the presence and severity of OSA, particularly in
      males.

PMID- 21080090
TI  - XAS study of lead speciation in a central Italy calcareous soil.
AB  - PURPOSE: The Pb absorption processes on a heavy textured calcareous soil, typical
      of central Italy, were studied using synchrotron X-ray absorption spectroscopy
      (XAS) in order to probe, at molecular scale, the structure and chemical nature of
      Pb in contaminated soils and achieve precise description of Pb ions localization
      into these contaminated soils. MATERIALS AND METHODS: In order to distinguish the
      role of the different components of soils in Pb retention, samples were prepared
      from the original soils removing the carbonate fractions, the organic matter, the
      metal oxides, or selecting the clay fractions. Then these samples were fortified
      with Pb simulating the natural interactions processes of heavy metal solutions
      with soils. The quantitative analysis of near edge (XANES) as well extended
      (EXAFS) regions of Pb L(III) edge absorption spectra, in comparison with Pb XAS
      data of selected reference compounds, allowed the precise determination of local
      structure and chemical environment of Pb ions in these soil samples. RESULTS:
      Four components were individuated as the major responsible of Pb retention in
      calcareous soils: the carbonates, the metal oxide surfaces, the organic matter,
      and the colloidal inorganic surfaces containing clay components. The structural
      analysis suggests that, within these experimental conditions, the Pb adsorbed on
      the soil is generally present as Pb hydroxide with poor crystallization degree.
      However, the presence of carbonates (CaCO3) induces the co-precipitation of PbCO3
      like phases with some degree of crystallinity.

PMID- 21080091
TI  - Trace element concentrations from lichen transplants in Pretoria, South Africa.
AB  - PURPOSE: The purpose of this study was to assess the level and possible sources
      of trace elements in Tshwane metropolis using transplanted lichen thallus of
      Parmelia sulcata with a view to evaluating the ability of this lichen species to
      monitor air pollutants from a perceived polluted environment. METHODS: Samples of
      the lichen thalli were transplanted into ten different sites and covered with a
      net. Samples were exposed for 3 months. Concentrations of ten trace elements were
      determined with the use of inductively coupled plasma mass spectrometry. RESULTS:
      A significant difference was observed in the values of elemental concentration in
      lichen from unpolluted area and those transplanted to all the sites (p < 0.01).
      Variations in values of trace elements recorded in lichen transplant from
      different sites were also statistically significant (p < 0.01). The high traffic
      sites showed significantly higher elemental concentrations, particularly for Pb,
      Zn, and Cu than the industrial and residential areas (p < 0.05). CONCLUSION:
      Trends in the trace element values from different sites suggested that the
      elements might have come from anthropogenic sources.

PMID- 21080092
TI  - The Nightingale Prize 2010 for best MBEC paper in 2009 awarded.

PMID- 21080093
TI  - Measurements of steady flow through a bileaflet mechanical heart valve using
      stereoscopic PIV.
AB  - Computational modeling of bileaflet mechanical heart valve (BiMHV) flow requires
      experimentally validated datasets and improved knowledge of BiMHV fluid
      mechanics. In this study, flow was studied downstream of a model BiMHV in an
      axisymmetric aortic sinus using stereoscopic particle image velocimetry. The
      inlet flow was steady and the Reynolds number based on the aortic diameter was
      7600. Results showed the out-of-plane velocity was of similar magnitude as the
      transverse velocity. Although additional studies are needed for confirmation,
      analysis of the out-of-plane velocity showed the possible presence of a four-cell
      streamwise vortex structure in the mean velocity field. Spatial data for all six
      Reynolds stress components were obtained. Reynolds normal stress profiles
      revealed similarities between the central jet and free jets. These findings are
      important to BiMHV flow modeling, though clinical relevance is limited due to the
      idealized conditions chosen. To this end, the dataset is publicly available for
      CFD validation purposes.

PMID- 21080095
TI  - What we've got here is a failure to communicate.

PMID- 21080096
TI  - Gallstone ileus causing perforation of the sigmoid colon.
AB  - A rare case of a cholecystocolonic fistula causing gallstone ileus with
      perforation of the sigmoid colon is described.

PMID- 21080097
TI  - Metabolic syndrome after bariatric surgery. Results depending on the technique
      performed.
AB  - BACKGROUND: There is a lack of long-term studies for metabolic syndrome after
      bariatric surgery. Our aim is to show the evolution of the parameters that define
      the metabolic syndrome after bariatric surgery, up to 10 years of follow-up, in
      order to clarify what technique gets better results with fewer complications.
      METHODS: The IDF definition of the metabolic syndrome was used for this study.
      One hundred twenty-five morbid obese and superobese patients underwent vertical
      banded gastroplasty. Two hundred sixty-five morbid obese and superobese patients
      had biliopancreatic diversion (Scopinaro and modified biliopancreatic
      diversions), and 152 morbid obese patients underwent laparoscopic gastric bypass.
      A mean follow-up of up to 7 years was done in all groups. RESULTS: Prior to
      surgery, metabolic syndrome was diagnosed in 114 patients of Scopinaro group
      (76%), in 85 patients of modified biliopancreatic diversion group (73.9%), in 81
      patients of laparoscopic gastric bypass (53.4%), and in 98 patients of vertical
      banded gastroplasty (78.4%). When metabolic syndrome parameters were evaluated at
      7 years of follow-up, owing to weight gain, these results changed nearby to
      preoperative values in both laparoscopic gastric bypass and vertical banded
      gastroplasty groups. CONCLUSION: According to our results, the best technique to
      resolve metabolic syndrome is the modified biliopancreatic diversion. Due to its
      high morbidity, it only must be considered in superobese patients. In obese
      patients, the laparoscopic gastric bypass may be a less agressive choice, but it
      should be coupled with lifestyle changes to keep away from the weight gain in the
      long run. Restrictive procedures may be indicated only in a few well-selected
      cases.

PMID- 21080098
TI  - Coenzyme Q10, copper, zinc, and lipid peroxidation levels in serum of patients
      with chronic obstructive pulmonary disease.
AB  - Severity of chronic obstructive pulmonary disease (COPD) exacerbation is
      associated with increased level of copper (Cu), zinc (Zn), and lipid peroxidation
      (malodialdehyde, MDA). The aim of this study was to investigate the levels of
      lipid peroxidation, Coenzyme Q10 (CoQ10), Zn, and Cu in the COPD exacerbations.
      Forty-five patients with COPD acute exacerbation and 45 healthy smokers as
      control group were used in the study. Forced expiratory volume in 1 s (FEV1) and
      forced vital capacity (FVC) were lower in exacerbation group than in control. C-
      reactive protein levels, white blood cell count, and sedimentation rate were
      significantly (p<0.001) higher in patients than in control. CoQ10 level and Cu/Zn
      ratio was significantly (p<0.05) lower in patients than in control, although MDA,
      Cu, and Zn levels were significantly (p<0.05) higher in patients than in control.
      Negative correlations were found among MDA, Cu, Zn, FEV1, and FVC values in
      exacerbation and control subjects (p<0.05). In conclusion, we observed that
      oxidative stress in the exacerbation period of COPD patients was increased. The
      decrease in CoQ10 level and Cu/Zn ratio and elevation in Cu and Zn levels
      observed in the patients probably result from the defense response of organism
      and are mediated by inflammatory-like substances.

PMID- 21080099
TI  - Cross-talk between body iron stores and diabetes: iron stores are associated with
      activity and microsatellite polymorphism of the heme oxygenase and type 2
      diabetes.
AB  - To assess the relationship between the length of (GT)n repeats in HO-1 gene
      promoter and heme oxygenase (HO) enzymatic activity in mononuclear cells with
      iron (Fe) stores in type 2 diabetic mellitus (DM2) patients and metabolic
      syndrome (MS) subjects, we studied 163 patients with DM2, 185 with MS, and 120
      controls subjects. We evaluated iron status (hemoglobin and serum Fe, ferritin,
      and transferrin receptor), and we determined the length of (GT)n repeats in HO-1
      gene promoter by capillary electrophoresis and HO enzymatic activity in
      mononuclear cells and assessed the relationship between these results and Fe
      stores. Only 1/163, 6/185, and 7/120 had iron deficiency anemia in DM2 patients,
      MS subjects, and controls, respectively. No iron overload (ferritin>200 MUg/L)
      was detected in all the subjects studied. DM2 patients had higher iron deposits,
      total body iron, and heme oxygenase activity (a suggestion of high oxidative
      stress condition) than MS subjects and controls. In DM2, we found a positive
      association between serum iron and HO activity. There were no difference in
      allelic frequency between the three groups; however, among DM2 and MS patients,
      the frequency of short/medium (SM) genotype of (GT)n repetition was increased and
      medium/medium (MM) genotype of (GT)n repetition was lower than controls. These
      results imply that DM2 patients and individuals with MS carrying SM repeats might
      have higher susceptibility to develop diabetes consequences. This increased
      susceptibility could be Fe-mediated oxidative stress.

PMID- 21080100
TI  - Use of stringent selection parameters for the identification of possible selenium
      responsive marker genes in mouse liver and gastrocnemius.
AB  - Selenium is a trace element that, although toxic in higher concentrations, is
      essential for human and animal health. In this study, we looked at microarray
      based gene expression patterns from liver and gastrocnemius tissues in mice fed
      either a selenium-deficient diet or diets containing sodium selenite,
      selenomethionine, or a yeast-derived selenium supplement. A p value cutoff of
      0.01 was used to identify a select set of selenium-responsive genes that were
      consistently differentially expressed across three age groups of mice with both
      ANOVA and t test analyses. A total of 19 gene transcripts were found to be
      differentially expressed across the three age groups with at least one selenium
      deficient/selenium-supplemented diet comparison. Of those 19 genes, 12 had been
      previously identified as selenoprotein-encoding genes, and four of the genes,
      Gpx1, Selh, Sep15, and Sepw1, were differentially expressed in both tissues, all
      three mouse age groups, and all three diet comparisons. Activities associated
      with non-selenoproteins encoded by selenium-responsive genes included transport
      and stress response. The selenophosphate synthetase 2 gene Sephs2 in
      gastrocnemius tissue and the solute carrier gene Slc48a1 in liver tissue, both up
      regulated with selenium-deficient diets compared to all three selenium
      supplemented diets, are previously overlooked candidates for dietary selenium
      marker genes.

PMID- 21080101
TI  - Serum copper, zinc, and magnesium levels in patients with chronic fluorosis.
AB  - Although there are many studies on effect of fluoride on trace elements in
      experimental animals, few studies exist on serum trace elements levels in
      patients with endemic fluorosis. We aimed to determine the serum levels of trace
      elements including serum copper (Cu), zinc (Zn), and serum levels of minerals
      including calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium
      (K) in patients with endemic fluorosis. The study group consisted of 30 patients
      with endemic fluorosis (17 females, 13 males, mean age 33.53+/-9.85 years). An
      age, gender, and body mass index matched 30 healthy volunteers comprised control
      group (21 females, ten males with a mean age 33.93+/-7.39 years). Urine fluoride
      levels of chronic fluorosis patients were significantly higher than that of
      control subjects as expected (1.92+/-0.10 mg/l vs. 0.41+/-0.09 mg/l,
      respectively; P<0.001). Serum Cu levels (89.14+/-16.77 MUg/dL vs. 102.69+/-25.04
      MUg/dL, respectively, P=0.017), serum Zn levels (77.98+/-20.58 MUg/dL vs. 94.57+/
      35.87MUg/dL, respectively, P=0.032), and serum Mg levels (1.92+/-0.18 mg/dL vs.
      2.07+/-0.31 mg/dL, respectively, p=0.022) was significantly lower in chronic
      fluorosis patients than in controls. There were no statistically significant
      differences between the fluorosis group and control group with respect to serum
      levels of Na, K, Ca, and P. We concluded that chronic fluorosis is associated
      with reduced serum levels of Cu, Zn, and Mg.

PMID- 21080102
TI  - Solid-state fermentation of palm kernel cake with Aspergillus flavus in laterally
      aerated moving bed bioreactor.
AB  - Solid-state fermentation (SSF) was employed to enhance the nutritive values of
      palm kernel cake (PKC) for poultry feeding. Aspergillus flavus was isolated from
      local PKC and utilized to increase the mannose content of PKC via the degradation
      of beta-mannan in PKC; evaluation was done for batch SSF in Erlenmeyer flasks and
      in a novel laterally aerated moving bed (LAMB) bioreactor. The optimum condition
      for batch SSF in flasks was 110% initial moisture content, initial pH 6.0, 30 
      degrees C, 855 MUm particle size, and 120 h of fermentation, yielding 90.91 mg
      mannose g-1 dry PKC (5.9-fold increase). Batch SSF in the LAMB at the optimum
      condition yielded 79.61 mg mannose g-1 dry PKC (5.5-fold increase) within just 96
      h due to better heat and mass transfer when humidified air flowed radially across
      the PKC bed. In spite of a compromise of 12% reduction in mannose content when
      compared with the flasks, the LAMB facilitated good heat and mass transfer, and
      improved the mannose content of PKC in a shorter fermentation period. These
      attributes are useful for batch production of fermented PKC feed in an industrial
      scale.

PMID- 21080103
TI  - Catechol-O-methyltransferase (COMT) val158met polymorphism as a risk factor for
      PTSD after urban violence.
AB  - PTSD is a psychiatric disorder that requires a traumatic event as diagnostic
      criteria. Brazil has high rates of violence, and it is expected that urban
      victims of violence would be at risk to the development of PTSD. Studies have
      associated the COMT val158met polymorphism with diminished stress resilience,
      reduced ability to extinguish conditioned fear, and the development of PTSD after
      multiple traumatic experiences. The aim of this study was to identify, in a case
      control study, whether the val158met polymorphism (rs4860) is associated with the
      development of PTSD in a group of victims of urban violence. To our knowledge,
      this is the first study that examines the association between PTSD and urban
      violence. The polymorphism of COMT in PTSD patients (n=65) as well as in victims
      of violence without PTSD (n=34) and in a community control group (n=335) were
      genotyped. We found a significant relationship between the met allele (p<0.02)
      and PTSD among cases (PTSD+)and victims of violence without PTSD (PTSD-; OR 2.57)
      and between cases and community control group (p<0.003) Further analysis with
      larger samples and another ethnic group should be necessary to confirm our
      findings.

PMID- 21080104
TI  - CRM197-induced blood-brain barrier permeability increase is mediated by
      upregulation of caveolin-1 protein.
AB  - Cross-reacting material 197 (CRM197), a non-toxin mutant of diphtheria toxin,
      could act as a diphtheria toxin receptor-specific carrier protein for the
      targeted delivery of macromolecular substances across the blood-brain barrier
      (BBB) in vitro. This study was performed to investigate the effects and
      mechanisms of CRM197 on the permeability of BBB in guinea pigs. Data from the
      Evans blue extravasation showed that the BBB permeability significantly increased
      after CRM197 injection in a dose-dependent manner. Transmission electron
      microscopy indicated CRM197 could induce increased pinocytotic vesicles and
      vacuoles in brain microvascular endothelial cells. Immunohistochemistry and
      western blot assay revealed that CRM197 enhanced caveolin-1 protein expression in
      brain microvessels. The caveolin-1 protein in the membrane fraction of
      microvessels began to upregulate at 5 min and reached the peak at 10 min after
      CRM197 treatment, associated by diminished expression of several tight junction
      associated proteins ZO-1, occludin, and claudin-5. Thus, our results indicate
      that the in vivo targeting CRM197 leads to increased BBB permeability via
      upregulation of caveolin-1 protein, increased pinocytotic vesicles, and
      redistribution of tight junction-associated proteins in brain microvessels.
      CRM197 may have a potential application for targeted drug delivery across the
      BBB.

PMID- 21080106
TI  - In vitro functionality of isolated embryonic hypothalamic vasopressinergic and
      oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor
      and angiotensin II.
AB  - There are only a few studies on the ontogeny and differentiation process of the
      hypothalamic supraoptic-paraventriculo-neurohypophysial neurosecretory system. In
      vitro neuron survival improves if cells are of embryonic origin; however,
      surviving hypothalamic neurons in culture were found to express small and minimal
      amounts of arginine-vasopressin (AVP) and oxytocin (OT), respectively. The aim of
      this study was to develop a primary neuronal culture design applicable to the
      study of magnocellular hypothalamic system functionality. For this purpose, a
      primary neuronal culture was set up after mechanical dissociation of sterile
      hypothalamic blocks from 17-day-old Sprague-Dawley rat embryos (E17) of both
      sexes. Isolated hypothalamic cells were cultured with supplemented (B27)
      NeuroBasal medium containing an agent inhibiting non-neuron cell proliferation.
      The neurosecretory process was characterized by detecting AVP and OT secreted
      into the medium on different days of culture. Data indicate that spontaneous AVP
      and OT release occurred in a culture day-dependent fashion, being maximal on day
      13 for AVP, and on day 10 for OT. Interestingly, brain-derived neurotrophic
      factor (BDNF) and Angiotensin II (A II) were able to positively modulate
      neuropeptide output. Furthermore, on day 17 of culture, non-specific (high-KCl)
      and specific (Angiotensin II) stimuli were able to significantly (P < 0.05)
      enhance the secretion of both neuropeptides over respective baselines. This study
      suggests that our experimental design is useful for the study of AVP- and OT
      ergic neuron functionality and that BDNF and A II are positive modulators of
      embryonic hypothalamic cell development.

PMID- 21080108
TI  - Discrimination analysis of mass spectrometry proteomics for cervical cancer
      detection.
AB  - To study the serum protein fingerprint of patients with cervical cancer and to
      screen for protein molecules closely related to cervical cancer during the onset
      and progression of the disease using matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS). Serum samples from 85 patients
      with cervical cancer and 80 healthy volunteers. Weak cation exchange (WCX)
      magnetic beads and PBSII-C protein chips reader (Ciphergen Biosystems Ins.) were
      used.The protein fingerprint expression of all the serum samples and the
      resulting profiles between cancer and normal were analyzed with Biomarker Wizard
      system. A group of proteomic peaks were detected. Three differently expressed
      potential biomarkers were identified with the relative molecular weights of 3974
      Da, 4175 Da, 5906 Da. This diagnostic model can distinguish cervical cancer from
      healthy controls with a sensitivity of 93.3% and a specificity of 95%. Blind test
      data indicated a sensitivity of 87.5% and a specificity of 90%. MALDI technology
      can be used to screen significant proteins of differential expression in the
      serum of cervical cancer patients. These different proteins could be specific
      biomarkers of the patients with cervical cancer in the serum and have the
      potential value of further investigation.

PMID- 21080105
TI  - Intracerebral hemorrhage specific intensity of care quality metrics.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) care can vary among centers and
      previous studies have demonstrated differences in ICH outcome based on variations
      in patient care in various settings. The purpose of this paper is to present the
      design of an evidence-based dataset of elements of a new ICH specific intensity
      of care quality metrics. METHODS: The articles were identified based on personal
      knowledge of the subject supplemented by data derived from multi-center
      randomized trials, and selected non-randomized or observational clinical studies.
      The information was identified with multiple searches on MEDLINE from 1986
      through 2009. The current guidelines from American Heart Association
      (AHA)/American Stroke Association (ASA) Stroke Council and The European Stroke
      Initiative (EUSI) Writing Committee for management of ICH were reviewed
      extensively for identifying quality indicators and available scientific evidence.
      For certain elements where stroke-specific data was not available, data derived
      from other disease process with direct relevance was used. RESULTS: A total of 26
      quality indicators related to 18 facets of care with thresholds for quality
      response were identified. A pilot study was performed to asses and score 1300 (26
      indicator per patientX25 patientsX2 raters) quality indicators. The minimum
      proportion of patients meeting quality parameter ranged from 44% to 100%
      depending upon the variable. The lowest performance scores were observed in the
      early intubation and mechanical ventilation, treatment of significant
      intracranial mass effect or transtentorial herniation, and timely acquisition of
      neuroimaging. The highest performance scores were seen in treatment of any
      seizure within 2 weeks of admission, status epilepticus, and prevention of
      gastric ulcer. CONCLUSIONS: The next step in development of a new ICH specific
      intensity of care quality metrics is validation and refinement of the quality
      indicators and thresholds presented in the current report. Future activities may
      include selection and validation based on consensus of experts and application of
      the system to a large series of patients with ICH and assessment of relationship
      of components in isolation and as a group to outcome after severity adjustment.

PMID- 21080107
TI  - CK5/6, EGFR, Ki-67, cyclin D1, and nm23-H1 protein expressions as predictors of
      pathological complete response to neoadjuvant chemotherapy in triple-negative
      breast cancer patients.
AB  - The purpose of this study was to evaluate the importance of biological markers to
      predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in
      patients with locally advanced triple-negative breast cancers (TNBCs). Forty-one
      patients (18.6%) among 220 breast cancer patients were identified as TNBCs from
      March 2006 to 2009 were included in this prospective study. The pre-NCT treatment
      expression levels of Ki-67 proliferation index, estrogen receptor (ER),
      progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), CK5/6,
      epidermal growth factor receptor (EGFR), cyclin D1, and nm23-H1 were detected by
      immunohistochemistry (IHC). A total of 180 cycles were administered with the
      median number of four cycles per patient (range, 4-6). The pCR rate was 34.1%
      (95% CI, 19.6-48.6%). In univariate analysis, early T stage, clinical response
      after 2 cycles, negative basal-like, negative EGFR, high Ki-67 proliferation
      index, and positive nm23-H1 were found to be significantly predictive of a pCR (P
      = 0.010, 0.040, 0.007, 0.001, 0.019, and 0.010, respectively). Basal-like status
      and nm23-H1 status were significant for pCR on multivariate analysis (P = 0.004
      and 0.031, respectively). Basal-like status and nm23-H1 are independent
      predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination
      chemotherapy in patients with TNBCs.

PMID- 21080109
TI  - Overexpression of SGLT1 and EGFR in colorectal cancer showing a correlation with
      the prognosis.
AB  - Na+-dependent glucose cotransporter (SGLT1), reported overexpression in tumor
      tissues while its clinical significance was not established, and epidermal growth
      factor receptor (EGFR) with potential relation to SGLT1 were studied in order to
      investigate their clinical significance in colorectal cancer (CRC). Eighty-five
      patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center from March
      1st 2005 to December 31st 2008 were enrolled. SGLT1 and EGFR expression in these
      cancer tissues and 28 normal tissues were tested by immunohistochemistry. (1)
      Expression of SGLT1 (P = 0.00) and EGFR (P = 0.01) in cancer tissues was higher
      than that in normal tissues. (2) Their expression related with clinical stage (P
      = 0.03 and P = 0.02), but not with other clinical characteristics. (3) For first
      line chemotherapy, expression of SGLT1 (P = 0.06 and P = 0.21) and EGFR (P = 0.37
      and P = 0.31) had no influence on objective response rate (ORR) and disease
      control rate (DCR). EGFR overexpression was associated with lower disease-free
      survival (P = 0.00) and overall survival (P = 0.01), while SGLT1 did not (P =
      0.79 and P = 0.34). Conclusions Both SGLT1 and EGFR overexpression in CRC was
      related to higher clinical stages. SGLT1 had a potential impact on the ORR of
      first-line chemotherapy in CRC. EGFR was associated with prognosis, while SGLT1
      did not.

PMID- 21080110
TI  - Investigation on the utility of permanent maxillary molar cusp areas for sex
      estimation.
AB  - Digital photogrammetric methods were employed to assess the level of sexual
      dimorphism present in permanent maxillary molar cusp areas of black South
      Africans (130 males, 105 females). Odontometric standards were then developed for
      diagnosing sex, based on the cusp area data derived for these teeth. Results
      demonstrated that all cusp area measurements of both the first and second
      maxillary molars were significantly dimorphic (P < 0.0001) in this group.
      Univariate and multivariate discriminant function analyses yielded overall sex
      prediction accuracy rates between 59.6 and 74.5%. Comparable allocation results
      were also obtained for binary logistic regression analyses, but with larger
      classification sex biases. The highest classification accuracies were observed
      for different combinations of just two cusp areas for the first molar. Allocation
      rates of formulae derived for second molar dimensions were on average 4.3% lower
      than those obtained for the first molar. Analyses incorporating cusp areas of
      both maxillary molars did not improve classification accuracies achieved when
      only using first molar measurements. The classification rates are below the
      suggested minimum accuracy of 75-80% for reliable forensic application of a
      method; however, the derived formulae may provide a useful statistical indication
      as to the sex of fragmentary remains in which complete or even partial tooth
      crowns are the only materials available for examination. Furthermore, the
      formulae can be applied not only to adults but also to subadults (above the age
      of 3 years) in which the more accurate sex discriminating features of the pelvis
      and skull are yet to develop.

PMID- 21080111
TI  - CT perfusion: ready for prime time.
AB  - Advancements in computed tomography (CT) technology have revolutionized clinical
      practice, particularly regarding the noninvasive assessment of coronary artery
      disease (CAD). The versatility of cardiac CT has rendered multiple applications
      including assessment of cardiac structure and function, myocardial viability, and
      coronary anatomy. The merits of cardiac computed tomography angiography (CTA)
      have been proven for the detection, and particularly the exclusion, of CAD.
      However, CTA becomes limited in the presence of significant CAD. Its inability to
      consistently identify lesion-associated ischemia may necessitate additional
      radionuclide myocardial perfusion imaging. Myocardial computed tomography
      perfusion imaging (CTP) has emerged as a useful and convenient method to
      immediately assess myocardial ischemia. In this review, we discuss the current
      state of CTP including available technology, its performance to date from current
      literature, and future challenges to this field.

PMID- 21080112
TI  - Treatment of chronic migraine.
AB  - Chronic migraine is defined in different ways. The most commonly used definition
      is headache on more than 15 days per month in patients with migraine. Chronic
      migraine is difficult to treat and requires a multidisciplinary approach. Only
      two pharmacological treatments have been shown to be effective in placebo
      controlled randomized trials: topiramate and local injection of botulinum toxin.
      Both therapies are effective in patients with chronic migraine with and without
      medication overuse. Many other substances have been investigated in chronic daily
      headache. All trials were underpowered and, therefore, recommendations concerning
      possible efficacy are not possible.

PMID- 21080113
TI  - Update on hemicrania continua.
AB  - Hemicrania continua (HC) is a rare primary headache syndrome, characterized by
      unilateral pain and an absolute response to indometacin. Since the term was first
      coined in 1984, more than 100 cases have been described worldwide. Most recently,
      detailed case series that provide more detailed information concerning the
      sometimes complex clinical presentation of HC have been reported. Functional
      imaging studies suggest a unique pattern of subcortical involvement in HC:
      contralateral to the pain posterior hypothalamic region, ipsilateral dorsal pons
      and ipsilateral ventral midbrain, which, along with the particular effect of
      indometacin, probably justifies its classification as a unique entity. Increasing
      the awareness of this primary headache form among clinicians will aid in its
      diagnosis while further work is being undertaken to characterize the syndrome.

PMID- 21080114
TI  - Statins in combinations: from ARBITER-6 HALTS to ACCORD--what works?

PMID- 21080115
TI  - Tinnitus-related distress: A review of recent findings.
AB  - This article reviews recent articles relevant to tinnitus-related distress (TRD).
      Recent studies provide evidence that 1) chronic tinnitus, which occurs in a
      significant percentage of adults, has stress-inducing effects similar to those of
      other chronic health problems; 2) the effects of tinnitus on distress are worse
      in individuals who have certain personality characteristics, such as type D
      personality and anxiety sensitivity; 3) neural activity in TRD is similar to that
      for pain and depression; 4) tinnitus leads to less distress in individuals who
      accept their condition; and 5) cognitive-behavioral treatments, including
      relaxation training, attention-control training, and acceptance activities, tend
      to reduce TRD. The recent findings suggest that it would be good practice for
      mental health professionals to ask patients, especially older patients, about
      tinnitus and to offer psychological treatment for TRD in appropriate cases.
      Future research on TRD might explore the extent to which the problem is genetic
      and the possibility of preventing TRD in individuals who have recently developed
      persistent tinnitus.

PMID- 21080116
TI  - Patient profiling for treatment toxicity: potential use of clinical and genomic
      factors.
AB  - Significant advances have been made in the identification of genes associated
      with the occurrence and prognosis of a variety of cancers. Recent efforts have
      also identified specific genomic single nucleotide polymorphisms (SNPs) that are
      associated with treatment toxicity in oncology, including toxicity associated
      with irinotecan, 5-FU, and 6-mercaptopurine. Despite the identification of these
      potential genomic predictors, their clinical use has been limited. Recent work
      has identified combined clinical characteristics and SNPs associated with
      toxicity with temozolomide. This combined approach may allow for identification
      of those at risk, and by using clinical parameters for screening, further refine
      those who require the more expensive genomic testing. This approach, as well as
      evaluation of clinical utility, economic impact, and ease of use are important
      components necessary for evaluation and use of genomic predictors of toxicity in
      the future.

PMID- 21080117
TI  - Obesity and cancer risk: recent review and evidence.
AB  - The prevalence of overweight and obesity is increasing worldwide, and the
      evidence base for a link between obesity and cancer is growing. In the United
      States, approximately 85,000 new cancer cases per year are related to obesity.
      Recent research has found that as the body mass index increases by 5 kg/m2,
      cancer mortality increases by 10%. Additionally, studies of patients who have had
      bariatric surgery for weight loss report reductions in cancer incidence and
      mortality, particularly for women. The goal of this review is to provide an
      update of recent research, with a focus on epidemiologic studies on the link
      between obesity and cancer. In addition, we will briefly review hypothesized
      mechanisms underlying the relationship between obesity and cancer. High
      priorities for future research involve additional work on the underlying
      mechanisms, and trials to examine the effect of lifestyle behavior change and
      weight loss interventions on cancer and intermediate biomarkers.

PMID- 21080118
TI  - Alternation learning in pathological gamblers: an fMRI Study.
AB  - OBJECTIVES: We have previously reported that pathological gamblers have impaired
      performance on the Stroop color word naming task, go-no-go task and speed
      accuracy tradeoff performance, tasks used to assess executive function and
      interference control. The aim of the present neuroimaging study was to explore
      the relationship between frontal cortex function and gambling severity in
      pathological gamblers. MATERIALS AND METHODS: Functional MRI (fMRI) was used to
      estimate brain activity of ten male medication-free pathological gamblers during
      performance of an alternation learning task. Performance of this task has been
      shown to depend on the function of regions in the frontal cortex. RESULTS: The
      executive functions needed to perform the alternation learning task were
      expressed as brain activation in lateral and medial frontal as well as parietal
      and occipital regions. By correlating the level of local brain activation to task
      performance, parietal regions and lateral frontal and orbitofrontal regions were
      demonstrated. A higher score in SOGS was associated with intrusion on the task
      specific activation in the left hemisphere, to some extant in parietal regions
      and even more pronouncedly in left frontal and orbitofrontal regions.
      CONCLUSIONS: Our preliminary data suggests that pathological gambling may be
      characterized by specific neuro-cognitive changes related to the frontal cortex.

PMID- 21080119
TI  - Deep-inspiration breath-hold PET/CT versus free breathing PET/CT and respiratory
      gating PET for reference: evaluation in 95 patients with lung cancer.
AB  - OBJECTIVE: The objective of this study was to define the factors that correlate
      with differences in maximum standardized uptake value (SUV(max)) in deep
      inspiration breath-hold (DIBH) and free breathing (FB) PET/CT admixed with
      respiratory gating (RG) PET for reference. METHODS: Patients (n = 95) with
      pulmonary lesions were evaluated at one facility over 33 months. After undergoing
      whole-body PET/CT, a RG PET and FB PET/CT scans were obtained, followed by a DIBH
      PET/CT scan. All scans were recorded using a list-mode dynamic collection method
      with respiratory gating. The RG PET was reconstructed using phase gating without
      attenuation correction; the FB PET was reconstructed from the RG PET sinogram
      datasets with attenuation correction. Respiratory motion distance, breathing
      cycle speed, and waveform of RG PET were recorded. The SUV(max) of FB PET/CT and
      DIBH PET/CT were recorded: the percent difference in SUV(max) between the FB and
      DIBH scans was defined as the %BH-index. RESULTS: The %BH-index was significantly
      higher for lesions in the lower lung area than in the upper lung area.
      Respiratory motion distance was significantly higher in the lower lung area than
      in the upper lung area. A significant relationship was observed between the %BH
      index and respiratory motion distance. Waveforms without steady end-expiration
      tended to show a high %BH-index. Significant inverse relationships were observed
      between %BH-index and cycle speed, and between respiratory motion distance and
      cycle speed. CONCLUSION: Decrease in SUV(max) of FB PET/CT was due to (1) tumor
      size, (2) distribution of lower lung, (3) long respiratory movement at slow
      breathing cycle speeds, and (4) respiratory waveforms without steady end
      expiration.

PMID- 21080120
TI  - Omission of [(15)O]CO scan for PET CMRO(2) examination using (15)O-labelled
      compounds.
AB  - OBJECTIVE: CBF, OEF and CMRO(2) provide us important clinical indices and are
      used for assessing ischemic degree in cerebrovascular disorders. These
      quantitative images can be measured by PET using (15)O-labelled tracers such as
      C(15)O, C(15)O(2) and (15)O(2). To reduce the time of scan, one possibility is to
      omit the use of CBV data. The present study investigated the influence of fixing
      the CBV to OEF and CMRO(2) values on subjects with and without cerebrovascular
      disorders. METHODS: The study consisted of three groups, namely, GROUP-0 (n =
      10), GROUP-1 (n = 9), and GROUP-2 (n = 10), corresponding to--without significant
      disorder, with elevated CBV, and with reduced CBF and elevated OEF, respectively.
      All subjects received PET examination and using the PET data OEF and CMRO(2)
      images were computed by fixing CBV and with CBV data. The computed OEF and
      CMRO(2) values were compared between the methods. RESULTS: The OEF and CMRO(2)
      values obtained by fixing the CBV were around 10% underestimation against that
      with CBV data. The regression analysis showed that these values were comparable
      (r = 0.93-0.98, P < 0.001). The simulation showed that fixing of the CBV would
      not derive significant error in either OEF or CMRO(2) values, when changed from 0
      to 0.08 ml/g. CONCLUSION: This study shows the feasibility of fixing the CBV
      value for computing OEF and CMRO(2) values in the PET examination, suggesting the
      CO scan could be eliminated.

PMID- 21080122
TI  - Diagnostic role of initial renal cortical scintigraphy in children with the first
      episode of acute pyelonephritis.
AB  - OBJECTIVE: Assessment of the first febrile urinary tract infection (UTI) in
      children has been the subject of debate for many years. Diagnosis of acute
      pyelonephritis (APN) is usually based on clinical and biological data. The
      clinical usefulness of early Tc-99m DMSA scintigraphy remains controversial,
      although it may influence the type and duration of treatment. The aim of this
      study was to assess the role of initial cortical scintigraphy in the detection of
      early renal parenchymal damage in children highly suspected of having APN and to
      compare the scintigraphic findings with selected clinical/laboratory parameters
      and ultrasonography. METHODS: A prospective study was conducted in 34 infants and
      young children (18 boys, 16 girls), aged 1.5-36 months (mean 9.8 +/- 8.7 months),
      hospitalized with a first episode of clinically suspected APN. Within the first 5
      days after admission, Tc-99m DMSA renal scintigraphy, ultrasonography (US),
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell
      count (WBC) and urine analyses were performed. RESULTS: DMSA scintigraphy showed
      changes consistent with APN in 27/34 (79%) patients, with a mean age of 10.9
      months, including 12 males (44%) and 15 (56%) females. Out of 9 febrile children
      with negative urine culture and supportive evidence of UTI, scintigraphy showed
      parenchymal involvement in 8 children (24% in the whole group, 30% in
      scintigraphically documented APN). There were no statistically significant
      correlations between the frequency or size of the initial scintigraphic
      abnormalities and age, sex, body temperature, CRP levels or ESR. A CRP level of
      >54 mg/L and a WBC of >13,300/mm3 had sensitivities of 56 and 59% and
      specificities of 86 and 71%, respectively. US showed changes consistent with APN
      in 7/34 (21%) in the whole group and in 7/27 (26%) patients with positive
      cortical scan (p < 0.05). CONCLUSION: Initial DMSA renal scintigraphy is a
      sensitive method for the early diagnosis of APN in young children and is useful
      in the assessment of the severity of kidney injury even in patients with negative
      urine culture. Clinical, biological and ultrasound parameters do not identify
      children with renal damage. Normal DMSA study, excluding parenchymal involvement
      and late sequelae, could minimize the use of scintigraphy in the follow-up and
      reduce the redundancy of cystography.

PMID- 21080123
TI  - Update on antiphospholipid syndrome in children.
AB  - Thrombotic events that occur in children are relatively rare and are mostly
      associated with indwelling catheters, infectious processes, surgical procedures,
      or genetic defects or deficiencies. However, case reports, case series, and
      registries continue to report children who exhibit the clinical features often
      associated with the antiphospholipid syndrome. Many of these cases are well
      documented and also meet the published research criteria for the antiphospholipid
      syndrome. Children with antiphospholipid antibodies generally do not experience a
      high rate of thrombotic events. This is in part related to developmental
      differences in levels of coagulation proteins and to the relative health of the
      vascular endothelium compared with that of adults. Therapeutic issues in children
      may be oriented more toward identifying risk factors and providing preventive
      health, as well as more short-term treatment of transient events.

PMID- 21080124
TI  - Nonpharmacologic treatments for migraine and tension-type headache: how to choose
      and when to use.
AB  - OPINION STATEMENT: There are a variety of nonpharmacologic treatments for
      headache. Educating patients about headache and its management, identifying and
      managing triggers (via diaries), modifying lifestyles, and understanding the
      importance of adopting and adhering to interventions (either pharmacologic or
      nonpharmacologic) are relevant to all persons with headache. In addition,
      specific nonpharmacologic treatments can be used either alone or in conjunction
      with ongoing pharmacologic intervention. Strong candidates for nonpharmacologic
      treatment include individuals with significant headache-related disability,
      comorbid mood or anxiety disorders, difficulty managing stress or other triggers,
      medication overuse, and patients who prefer a specific treatment. Behavioral
      treatments (relaxation, biofeedback, and cognitive-behavioral therapy) possess
      the most evidence for successful headache management. They have a long history of
      randomized trials showing efficacy and are considered first-line preventive
      options. Among complementary and alternative treatments, recent positive findings
      from randomized trials using acupuncture provide evidence of its potential as a
      first-line intervention. Other complementary and alternative techniques do not
      have a consistent base of research to recommend them for headache prevention, but
      they may be used if the patient prefers this approach or when other first-line
      interventions (nonpharmacologic or pharmacologic) have not provided adequate
      results. Among "natural" treatments, both butterbur extract and vitamin B2 have
      shown efficacy in more than one randomized trial and are thus potentially useful
      first-line preventive interventions.

PMID- 21080125
TI  - Interferon-alpha and zidovudine for relapsed/refractory adult T cell
      leukemia/lymphoma: case reports of Japanese patients.
AB  - Combination therapy with interferon-alpha and zidovudine (IFN/AZT) has been
      regarded as standard care for acute and indolent (i.e., chronic and smouldering)
      ATL based on reports involving a limited number of patients. This treatment
      approach has not been evaluated in Japan, a major endemic area of this disease in
      the world. This is the first Japanese report of IFN/AZT for ATL. It is impossible
      to draw any definitive conclusion from this small study; however, IFN/AZT showed
      clear anti-ATL effects for refractory/relapsed ATL patients. This report would
      contribute for developing future ATL treatment in Japan.

PMID- 21080126
TI  - Precursor B cell lymphoblastic lymphoma presenting as a solitary bone tumor: a
      case report and review of the literature.
AB  - Precursor B cell lymphoblastic lymphoma (B-LBL) is quite uncommon and it usually
      manifests as an extranodal disease. Although B-LBL may present with bone
      involvement, it is a very rare manifestation of B-LBL as a primary solitary bone
      tumor. Here, we report a case of precursor B-LBL presenting with solitary bone
      tumor and a review of a total of seven adult patients reported previously in the
      literature. We described demographic and clinical characteristics of these
      patients with unique presentation and discussed treatment options. Unlike
      previous reports except one case, our patient underwent allogeneic stem cell
      transplantation (allo-SCT) due to refractory disease. She is alive without
      evidence of disease by the post-transplant 12th month. B-LBL has an aggressive
      clinical course in adult patients and allo-SCT may be the best treatment option.

PMID- 21080127
TI  - Can implant retention be recommended for treatment of infected TKA?
AB  - BACKGROUND: Retention treatment is reportedly associated with lower infection
      control rates than two-stage revision. However, the studies on which this
      presumption are based depend on comparisons of historical rather than concurrent
      controls. QUESTIONS/PURPOSES: We (1) asked whether the infection control rates,
      number of additional procedures, length of hospital stay, and treatment duration
      differed between implant retention and two-stage revision treatment; and (2)
      identified risk factors that can contribute to failure of infection control.
      METHODS: We reviewed the records of 60 patients treated for 64 infected TKA from
      2002 to 2007. Twenty-eight patients (32 knees) underwent debridement with
      retention of component, and 32 patients (32 knees) were treated with component
      removal and two-stage revision surgery. We determined patients' demographics,
      type of infection, causative organisms, and outcome of treatment. Mean followup
      was 36 months (range, 12-84 months). RESULTS: Infection control rate was 31% in
      retention and 59% in the removal group after initial surgical treatment, and 81%
      and 91% at latest followup, respectively. Treatment duration was shorter in the
      retention group and there was no difference in number of additional surgeries and
      length of hospital stay. Type of treatment (retention versus removal) was the
      only factor associated with infection control; subgroup analysis in the retention
      group showed Staphylococcus aureus infection and polyethylene nonexchange as
      contributing factors for failure of infection control. CONCLUSIONS: Although
      initial infection control rate was substantially lower in the retention group
      than the removal group, final results were comparable at latest followup. We
      believe retention treatment can be selectively considered for non-S. aureus
      infection, and when applied in selected patients, polyethylene exchange should be
      performed. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 21080128
TI  - Does trochanteric transfer eliminate the Trendelenburg sign in adults?
AB  - BACKGROUND: Premature closure of the proximal femoral growth plate results in
      coxa brevis, which usually is associated with insufficiency of the hip abductors.
      Distal and lateral transfer of the greater trochanter sometimes is recommended to
      correct this problem. Most of what is known arises from studies of children and
      adolescents. QUESTIONS/PURPOSES: We asked whether this procedure in adults with
      coxa brevis would eliminate hip abductor insufficiency and would improve their
      hip function based on the Harris hip score (HHS). PATIENTS AND METHODS: We
      prospectively followed 11 patients, aged 19 to 55 years (mean, 40 years) who had
      distal and lateral trochanteric transfer. All patients had pain and a positive
      Trendelenburg test before surgery. This test was performed at the latest followup
      by three observers and the interobserver reliability was determined by the kappa
      coefficient. The HHS was obtained before surgery and at the latest followup. The
      minimum followup was 25 months (mean, 52 months; range, 25-77 months). RESULTS:
      Insufficiency of the hip abductors was eliminated in seven (according to two
      observers) and eight (according to one observer) of the 11 patients after
      surgery; the kappa coefficient ranged from 0.79 to 1.0. The mean HHS improved
      from 64 points preoperatively to 76 points at the final followup. The two
      patients with preexisting severe osteoarthritis of the hip had the worst final
      scores and persisted with a positive Trendelenburg test at the final followup.
      CONCLUSIONS: Distal and lateral transfer of the greater trochanter can eliminate
      insufficiency of the hip abductors and improve joint function in adult patients
      with coxa brevis and we believe should be considered for patients without severe
      osteoarthritis of the hip. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      the Guidelines for Authors for a complete description of levels of evidence.

PMID- 21080129
TI  - Spinal cord injury: a systematic review of current treatment options.
AB  - BACKGROUND: Spinal cord injury (SCI) is a devastating event often resulting in
      permanent neurologic deficit. Research has revealed an understanding of
      mechanisms that occur after the primary injury and contribute to functional loss.
      By targeting these secondary mechanisms of injury, clinicians may be able to
      offer improved recovery after SCI. QUESTIONS/PURPOSES: In this review, we
      highlight advances in the field of SCI by framing three questions: (1) What is
      the preclinical evidence for the neuroprotective agent riluzole that has allowed
      this agent to move into clinical trials? (2) What is the preclinical evidence for
      Rho antagonists that have allowed this group of compounds to move into clinical
      trials? (3) What is the evidence for early surgical decompression after SCI?
      METHODS: We conducted a systematic review of MEDLINE and EMBASE-cited articles
      related to SCI to address these questions. RESULTS: As a result of an improved
      understanding of the secondary mechanisms of SCI, specific clinical strategies
      have been established. We highlight three strategies that have made their way
      from bench to bedside: the sodium-glutamate antagonist riluzole, the Rho
      inhibitor Cethrin, and early surgical decompression. Each of these modalities is
      under clinical investigation. We highlight the fundamental science that led to
      this development. CONCLUSIONS: As our understanding of the fundamental mechanisms
      of SCI improves, we must keep abreast of these discoveries to translate them into
      therapies that will hopefully benefit patients. We summarize this process of
      bench to bedside with regard to SCI.

PMID- 21080131
TI  - 50 years ago in CORR: X-ray projections of anatomic structures in the cervical
      and lumbar vertebrae Raymond G. Tronzo MD CORR 1960;16:249-263.

PMID- 21080130
TI  - Structural allograft as an option for treating infected hip arthroplasty with
      massive bone loss.
AB  - BACKGROUND: Revision of the infected hip arthroplasty with major bone loss is
      difficult. Attempts to restore bone stock with structural allograft are
      controversial. QUESTIONS/PURPOSES: We assessed the (1) reinfection rate; (2)
      rerevision rate; (3) radiographic graft union, resorption, and implant migration;
      (4) Harris hip scores at 1 year and at last followup compared with before
      surgery; and (5) other major complications associated with the use of bulk
      structural allograft to treat massive bone loss in infected hip arthroplasty.
      METHODS: We retrospectively reviewed 27 patients who underwent two-stage revision
      arthroplasty using structural allograft to treat massive bone defects in infected
      hip arthroplasty. There were 17 proximal femoral grafts, three acetabular major
      column grafts, two acetabular minor column grafts, and 10 cortical strut grafts
      used. Five patients had combinations of two allografts. The minimum followup was
      1.1 years (mean, 8.2 years; range, 1.1-16.8 years). RESULTS: One of 27 patients
      had reinfection. The Kaplan-Meier survivorship was 93% at 10 years with
      rerevision for aseptic loosening as the end point. Radiographically, three
      patients had nonunion at the graft-host junction. All patients except two had
      graft resorption, of which all were mild except two, which were severe. Three
      patients had implant migration. The mean modified Harris hip scores were 39.2
      points (range, 25-60) preoperatively, 67.3 points (range, 40-91) at 1-year
      followup, and 70.3 points (range, 46-81) at last followup. Other major
      complications included one patient with dislocation and one patient with
      transient sciatic nerve injury. CONCLUSIONS: Based on our data, we believe the
      use of structural allografts is a reasonable option for treating massive bone
      loss in infected hip arthroplasties. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 21080132
TI  - The classic: Multiple fractures in the long bones of infants suffering from
      chronic subdural hematoma. 1946.

PMID- 21080133
TI  - Papers presented at the Annual Meetings of the Knee Society: editorial comment.

PMID- 21080134
TI  - Orphanage at the FDA.

PMID- 21080135
TI  - Translating nucleic acid aptamers to antithrombotic drugs in cardiovascular
      medicine.
AB  - Nucleic acid aptamers offer several distinct advantages for the selective
      inhibition of protein targets within the coagulation cascade. A highly attractive
      feature of aptamers as antithrombotics is their ability to encode for
      complementary "controlling agents" which selectively bind to and neutralize their
      active counterparts via Watson-Crick base pairing or, in a less selective and
      clinically characterized manner, cationic polymers that can counteract the
      activity of an aptamer or free/protein-complexed nucleic acid. The former
      property allows aptamer-based antithrombotic therapies to be administered with a
      goal of selective, high intensity target inhibition, knowing that rapid drug
      reversal is readily available. In addition, by purposefully varying the ratio of
      active agent to a specific controlling agent administered, the intensity of
      antithrombotic therapy can be regulated with precision according to patient needs
      and the accompanying clinical conditions. REG1, currently undergoing phase 2B
      clinical investigation, consists of an RNA aptamer (RB006; pegnivacogin) which
      targets factor IXa and its complementary controlling agent (RB007; anivamersen).
      Aptamers directed against other serine coagulation proteases, some with and some
      without parallel controlling agents, have been designed. Aptamers directed
      against platelet surface membrane receptor targets are in preclinical
      development. The following review offers a contemporary summary of nucleic acid
      aptamers as a translatable platform for regulatable antithrombotic drugs
      expanding the paradigm of patient- and disease-specific treatment in clinical
      practice.

PMID- 21080136
TI  - Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via
      increase of HSP70 and inhibition of NF-kappaB.
AB  - It has been reported that pretreatment of rats with lipopolysaccharide (LPS)
      increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts.
      However, the mechanisms by which LPS induces cardioprotection against I/R injury
      have not been fully elucidated. In this study, we pretreated rats with LPS (1.0
      mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles
      of heat shock protein-70 (HSP70) and nucleus factor-kappaB (NF-kappaB) in LPS
      induced cardioprotection. We observed that pretreatment with low-dose LPS
      resulted in significantly increased levels of HSP70 in the myocardium, which
      could dramatically inhibit NF-kappaB translocation and reduce degradation of
      inhibitory kappaB. Inhibition of NF-kappaB, in turn, attenuated release of
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1beta, and
      IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury.
      Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To
      further investigate whether increase of HSP70 might be responsible for protection
      of the myocardium against I/R injury, we co-administered the HSP70 inhibitor,
      quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection
      was attenuated by co-administration with quercetin. Herein, we concluded that
      increased levels of HSP70 through LPS pretreatment led to inhibition of NF-kappaB
      activity in the myocardium after I/R injury. Our results indicated that LPS
      induced cardioprotection was mediated partly through inhibition of NF-kappaB via
      increase of HSP70, and LPS pretreatment could provide a means of reducing
      myocardial I/R injury.

PMID- 21080137
TI  - Response of mice to continuous 5-day passive hyperthermia resembles human heat
      acclimation.
AB  - Chronic repeated exposure to hyperthermia in humans results in heat acclimation
      (HA), an adaptive process that is attained in humans by repeated exposure to
      hyperthermia and is characterized by improved heat elimination and increased
      exercise capacity, and acquired thermal tolerance (ATT), a cellular response
      characterized by increased baseline heat shock protein (HSP) expression and
      blunting of the acute increase in HSP expression stimulated by re-exposure to
      thermal stress. Epidemiologic studies in military personnel operating in hot
      environments and elite athletes suggest that repeated exposure to hyperthermia
      may also exert long-term health effects. Animal models demonstrate that
      coincident exposure to mild hyperthermia or prior exposure to severe hyperthermia
      can profoundly affect the course of experimental infection and injury, but these
      models do not represent HA. In this study, we demonstrate that CD-1 mice
      continuously exposed to mild hyperthermia (ambient temperature ~37 degrees C
      causing ~2 degrees C increase in core temperature) for 5 days and then exposed to
      a thermal stress (42 degrees C ambient temperature for 40 min) exhibited some of
      the salient features of human HA, including (1) slower warming during thermal
      stress and more rapid cooling during recovery and (2) increased activity during
      thermal stress, as well as some of the features of ATT, including (1) increased
      baseline expression of HSP72 and HSP90 in lung, heart, spleen, liver, and brain;
      and (2) blunted incremental increase in HSP72 expression following acute thermal
      stress. This study suggests that continuous 5-day exposure of CD-1 mice to mild
      hyperthermia induces a state that resembles the physiologic and cellular
      responses of human HA. This model may be useful for analyzing the molecular
      mechanisms of HA and its consequences on host responsiveness to subsequent
      stresses.

PMID- 21080138
TI  - Changes in human skeletal muscle length during stimulated eccentric muscle
      actions.
AB  - Following eccentric exercise, increases in muscle length alter the length-tension
      relation of skeletal muscle. However, its unclear if this change occurs during
      eccentric exercise. Therefore, 70 eccentric actions of the knee extensors of one
      leg (with superimposed electrical stimulation) were performed at 100 degrees /s,
      from full extension to full flexion. Angle-specific eccentric force was recorded
      throughout. Force decreased at all angles although this was non-uniform. At 70
      degrees , force decreased by 25%, whereas at 130 degrees , force decreased by
      41%. Initial peak force was recorded at 100 degrees  (590 +/- 232 N); the
      exercise bout induced a 21% decrease in peak force and a 10 degrees  shift in the
      position of peak force production to 90 degrees . The rightward shift in the
      muscle length-tension relation thus occurred during eccentric exercise, where
      greater force loss at short muscle lengths suggested an eccentric-induced over
      stretching of sarcomeres.

PMID- 21080140
TI  - Comparison of natural and synthetic diamond X-ray detectors.
AB  - Diamond detectors are particularly well suited for dosimetry applications in
      radiotherapy for reasons including near-tissue equivalence and high-spatial
      resolution resulting from small sensitive volumes. However, these detectors have
      not become commonplace due to high cost and poor availability arising from the
      need for high-quality diamond. We have fabricated relatively cheap detectors from
      commercially-available synthetic diamond fabricated using chemical vapour
      deposition. Here, we present a comparison of one of these detectors with the only
      commercially-available diamond-based detector (which uses a natural diamond
      crystal). Parameters such as the energy dependence and linearity of charge with
      dose were investigated at orthovoltage energies (50-250 kV), and dose-rate
      dependence of charge at linear accelerator energy (6 MV). The energy dependence
      of a synthetic diamond detector was similar to that of the natural diamond
      detector, albeit with slightly less variation across the energy range. Both
      detectors displayed a linear response with dose (at 100 kV) over the limited dose
      range used. The sensitivity of the synthetic diamond detector was 302 nC/Gy,
      compared to 294 nC/Gy measured for the natural diamond detector; however, this
      was obtained with a bias of 246.50 V compared to a bias of 61.75 V used for the
      natural diamond detector. The natural diamond detector exhibited a greater
      dependency on dose-rate than the synthetic diamond detector. Overall, the
      synthetic diamond detector performed well in comparison to the natural diamond
      detector.

PMID- 21080139
TI  - Inhibitory effects of estrogens on digestive enzymes, insulin deficiency, and
      pancreas toxicity in diabetic rats.
AB  - Diabetes mellitus, with its attendant disorders and dysfunctional behaviors,
      constitutes a growing concern to the population of the world. With this concern
      in mind, the present study investigated the anti-diabetic and hypolipedimic
      potential of 17beta-estradiol (called E2), particularly in terms of its
      inhibitory effects on maltase, sucrase, lactase, and lipase activities in the
      intestine of surviving diabetic rats. The findings revealed that this supplement
      helped protect the beta cells of the rats from death and damage. Interestingly,
      E2 induced considerable decreases of 29%, 46%, 42%, and 84% in the activities of
      intestinal maltase, lactase, sucrase, and lipase, respectively. The E2 extract
      also decreased the glucose, triglyceride, and total cholesterol rates in the
      plasma of diabetic rats by 39%, 27%, and 53%, respectively, and increased the HDL
      cholesterol level by 74%, which helped maintain the homeostasis of blood lipid.
      When compared to those of the untreated diabetic rats, the superoxide dismutase,
      catalase, and glutathione peroxidase levels in the pancreas of the rats treated
      with this supplement were also enhanced by 330%, 170%, and 301%, respectively. A
      significant decrease was also observed in the lipid peroxidation level and
      lactate dehydrogenase activity in the pancreas of diabetic rats after E2
      administration. Overall, the findings presented in this study demonstrate that E2
      has both a promising potential with regard to the inhibition of intestinal
      maltase, sucrase, lactase, and lipase activities, and a valuable hypoglycemic and
      hypolipidemic function, which make it a potential strong candidate for industrial
      application as apharmacological agent for the treatment and prevention of
      hyperlipidemia, obesity, and cardiovascular diseases.

PMID- 21080141
TI  - Child safety: a neglected priority.

PMID- 21080142
TI  - Treatment of respiratory syncytial virus with palivizumab: a systematic review.
AB  - BACKGROUND: Palivizumab has proven efficacy for prophylaxis of respiratory
      syncytial virus (RSV) in infants with prematurity or congenital heart disease.
      Despite a paucity of data, palivizumab is sometimes used to prevent progression
      when high-risk patients present with upper respiratory tract infection (URTI) due
      to RSV, or as therapy when any patients present with severe lower respiratory
      tract infection (LRTI) caused by RSV. METHODS: A systematic review of the
      literatures on the use of palivizumab as therapy for RSV was conducted. The
      primary outcomes were progression from URTI to LRTI and survival rates. Secondary
      outcomes were adverse events due to palivizumab, serum palivizumab level, and RSV
      concentration in respiratory secretions. RESULTS: The search yielded 1 case
      report, 4 case series, and 2 randomized controlled trials (RCTs) with a total of
      136 adults and children. The RCTs were not powered to look at clinical outcomes.
      By combining all reported clinical outcomes, 3 (12%) of 25 patients with URTI who
      were given palivizumab died of RSV and 5 of 88 patients with LRTI at the time of
      treatment died of RSV (6%). Palivizumab levels appeared to be adequate for at
      least 3 weeks of intravenous injection at 15 mg/kg. The therapy resulted in
      decreased RSV concentrations in tracheal secretions. CONCLUSION: Larger RCTs will
      be required before palivizumab can be recommended as therapy for RSV in any
      clinical setting.

PMID- 21080144
TI  - A randomized, triple masked, placebo-controlled clinical trial for controlling
      childhood obesity.
AB  - BACKGROUND: The efficacy of pharmacological treatment in controlling childhood
      obesity is controversial. We aimed to compare the effects of three types of drug
      regimens and placebo on generalized and abdominal obesity among obese children
      and adolescents who did not succeed to lose weight 3 months after lifestyle
      modification (diet and exercise). METHODS: This triple-masked randomized clinical
      trial was conducted among 180 participants aged 10-16 years. They were assigned
      randomly to 4 groups of equal number to receive metformin, fluoxetine, a
      combination of the two drugs, or placebo. The trial lasted for 12 weeks and
      participants were followed up for an additional 12-week period. RESULTS: Overall,
      91.1% (n=164) of the enrolled participants completed the trial. After the 12-week
      trial, the body mass index decreased significantly in all groups receiving
      medications [approximately -1.2 (0.2) kg/m2, P<0.05]. This decrease was not
      significant in the placebo group. Waist circumference decreased significantly in
      the groups receiving metformin [-2.1 (0.4) cm, P=0.03)] as well as in the group
      receiving a combination therapy of metformin and fluoxetine [-2.5 (0.4) cm,
      P=0.01)]. In the 24-week follow-up study, these anthropometric indexes were lower
      than the baseline in the group that had received a combination therapy of
      metformin and fluoxetine. No serious drug side-effects were reported.
      CONCLUSIONS: A limited period of such treatment may help weight control, and
      might be used to encourage those children who have been refractory to weight loss
      for continuing the non-pharmacological programs. Our findings should be confirmed
      in future studies with a longer follow-up period.

PMID- 21080143
TI  - Foreign body ingestion: children like to put objects in their mouth.
AB  - BACKGROUND: Foreign body ingestion is a common problem in the pediatric age
      group. Infants and young children explore objects by putting them in the mouth.
      DATA SOURCES: We reviewed the most recent literatures regarding the incidence,
      clinical presentation, as well as the most recent advances in the diagnostic and
      therapeutic modalities of foreign body ingestion in children. RESULTS: In 2007
      more than 125 000 foreign body ingestions in patients of 19 years old and younger
      were reported to American Poison Control Centers in the USA. The majority of
      ingested foreign bodies pass spontaneously. CONCLUSIONS: Some foreign bodies can
      be harmful and require evaluation and intervention. The challenge in management
      is to distinguish the patients who require intervention from those who can be
      safely observed. In this review we suggest an algorithm for evaluation and
      management of children suspected to ingest a radiopaque foreign body.

PMID- 21080145
TI  - Cheatham-Platinum stent implantation for pulmonary artery stenosis in children
      and adolescents: immediate and mid-term outcome.
AB  - BACKGROUND: NuMED Cheatham-Platinum (CP) stent implantation for pulmonary artery
      stenosis in children and adolescents has been rarely reported. This study aimed
      to evaluate the immediate and mid-term results of CP stent implantation for the
      treatment of pulmonary artery stenosis associated with congenital heart disease
      (CHD) in children and adolescents. METHODS: From August 2005 to May 2007, four
      consecutive pediatric patients with pulmonary artery stenosis associated with CHD
      underwent CP stent implantation. They were followed up, and transthoracic
      echocardiography was done for outcome evaluation. RESULTS: In the four patients,
      5 stent placement procedures were performed and 7 CP stents were implanted (8
      zig, 22-39 mm in length). All stents except one were successfully placed in the
      target lesions without displacement during the procedures. After the procedure,
      the systolic pressure gradient across the stenosis decreased from 36.67 +/- 20.08
      to 3.67 +/- 3.20 mmHg (P=0.005), and the narrowest diameter of the stenotic
      segment increased from 6.97 +/- 2.22 to 13.40 +/- 4.40 mm (P=0.013). Two stents
      implanted in the left and right pulmonary arteries in patient 4 developed
      intrastent restenosis 6 months after the procedure, and the distal end of the
      main pulmonary artery also developed restenosis 26 months later. The results of
      the remaining stents have been stable without complications during a median
      follow-up of 34 months (range, 26-48 months). CONCLUSIONS: Our experience
      indicates that CP stent implantation is suitable for the treatment of pulmonary
      artery stenosis in children and adolescents with CHD. The immediate and mid-term
      results are encouraging, but long-term results demand further follow-up in more
      cases.

PMID- 21080146
TI  - Clinical characteristics, interdisciplinary treatment and follow-up of 14
      children with Takayasu arteritis.
AB  - BACKGROUND: Pediatric patients with Takayasu arteritis were studied by analyzing
      clinical presentation, diagnostic images, response to multimodal therapy, and
      long-term outcome. METHODS: Fourteen consecutive children and adolescents (mean
      age: 10 years) were diagnosed with Takayasu arteritis at our institution between
      1995 and 2007. They were subjected to clinical and diagnostic studies including
      color ultrasonography, MRI and angiography, and received interdisciplinary
      treatment. RESULTS: The median time lag between the first onset of symptoms and
      diagnosis was 7.7 weeks. The majority of patients presented with acute severe
      clinical symptoms and extensive vascular lesions. Hypertension was the most
      common finding on first presentation (93%), followed by headache (64%), nausea
      (64%) and palpitation (50%). Ten patients (71%) had reduced or absent carotid,
      brachial or femoral pulses in one or more locations. C-reactive protein was
      elevated in 79% of the patients and erythrocyte sedimentation rate in 64%.
      Cardiovascular imaging showed extensive vasculitis of both sides of the diaphragm
      in 86%. Complications included renal artery stenosis (n=7), aortic dissection,
      thoracic aortic aneurysm and infrarenal aneurysm (all n=1). Conservative drug
      treatment was effective in 50%. Interventional dilatation of stenosis and
      surgical therapy, including aortic bypass, resection of aneurysms and
      nephrectomy, were necessary in the remaining patients. Follow-up for 25 months to
      12 years showed that all children are well without disease-related mortality.
      CONCLUSIONS: Takayasu arteritis is a rare and potentially life-threatening
      disease in children, likely with a prolonged subclinical course. Rapid diagnosis
      and interdisciplinary management help to prevent life-threatening complications.

PMID- 21080148
TI  - Thiocyanate status does not play a role in the etiology of residual goiter in
      school children of Isfahan, Iran.
AB  - BACKGROUND: Despite long standing iodine supplementation in Iran the prevalence
      of goiter remains high in some areas. In the present study we investigated the
      possible role of thiocyanate as a goitrogen in the etiology of goiter in Isfahan,
      Iran. METHODS: A total of 2331 (6-13 year old) school children were selected by
      multistage random sampling. Thyroid size was estimated in each child by
      inspection and palpation. Urinary iodine concentration (UIC) and urinary
      thiocyanate (USCN) were measured. RESULTS: Overall, 32.9% of the 2331 students
      had goiter. The median UIC was 195.5 MUg/L. The mean +/- SD of USCN in goitrous
      and nongoitrous subjects was 0.42 +/- 0.28 mg/dL and 0.41 +/- 0.32 mg/dL,
      respectively (P=0.86). USCN level in goitrous and nongoitrous boys was 0.41 +/-
      0.32 mg/dL and 0.43 +/- 0.37 mg/dL, respectively (P=0.67). USCN level in goitrous
      and nongoitrous girls was 0.43 +/- 0.26 mg/dL and 0.40 +/- 0.28 mg/dL,
      respectively (P=0.43). CONCLUSIONS: Thiocyanate overload does not play a role in
      high prevalence of goiter in the studied population. We suggest the role of other
      goitrogenic factors should be investigated in this region.

PMID- 21080147
TI  - Novel CRELD1 gene mutations in patients with atrioventricular septal defect.
AB  - BACKGROUND: Atrioventricular septal defects (AVSDs) occur as clinical defects of
      several different syndromes, as autosomal dominant defects, and as sporadically
      occurring malformations. Consequently, there is genetic heterogeneity, but until
      recently, little is known about the genes involving in the pathogenesis of AVSD.
      CRELD1 gene, a novel cell adhesion molecule, is a candidate gene for AVSD.
      METHODS: This study included 133 patients with AVSD and 200 healthy controls.
      Peripheral blood samples were collected and genomic DNA was extracted from the
      leukocytes. CRELD1 was amplified by polymerase chain reaction (PCR) with specific
      primers. The sequences of PCR products were compared between the patients and
      controls. RESULTS: In a patient, a C-to-G transition was identified at nucleotide
      857 in exon 8 that resulted in a substitution of alanine for proline at amino
      acid 286 in the first calcium-binding EGF domain. This patient had an isolated
      partial AVSD and the mutation was inherited from her mother. Another mutation was
      detected in a patient with a partial AVSD and evidence of Down syndrome. The
      heterozygous c.973G>A transition in exon 9 resulted in a substitution of lysine
      for glutamic acid at amino acid 325 (E325K) in the second calcium-binding EGF
      domain. CONCLUSIONS: Two novel CRELD1 mutations were identified in the calcium
      binding EGF domain in patients with AVSD. CRELD1 is likely to be an AVSD
      susceptibility gene and CRELD1 mutations may increase the risk of developing a
      heart defect rather than being a direct causative mutation.

PMID- 21080149
TI  - A rare cause of intestinal perforation: ingestion of magnet.
AB  - BACKGROUND: Ingestion of foreign objects is a common problem in children.
      Ingestion of one more magnets may require surgical intervention because of risk
      of perforation. METHODS: A 4-year-old girl was admitted to our department with
      complaints of abdominal pain and bilious vomiting. She had been treated at
      another clinic with repeated abdominal X-rays because of ingestion of a magnet 5
      days ago. Physical examination revealed diffuse abdominal tenderness and bilious
      drainage from the nasogastric tube. The magnet was observed by radiopaque imaging
      in the right epigastric region of the upright abdomen but there was no free air.
      The magnet was presumed to be in the duodenum and exploratory laparotomy was
      performed. RESULTS: During the operation, a perforation was found between the
      pylorus and duodenum due to the magnet. The foreign body was found to be two
      magnets adherent to each; the interposed and compressed tissue was necrotized and
      perforated between the two magnets. The necrotized segment was excised and
      primary anastomosis was made. The postoperative period of the patient was
      uneventful and she was discharged on the seventh postoperative day. CONCLUSIONS:
      Ingestion of foreign objects such as one more magnets may cause intestinal
      perforation in early stages. If the object stays in the same location shown by
      repeated X-rays, surgical intervention should not be delayed.

PMID- 21080150
TI  - Is presentation of ADHD subtypes different between community and clinical
      samples?

PMID- 21080151
TI  - Macrophages and NF-kappaB in cancer.
AB  - Macrophages are tissue resident phagocytes with important roles in development,
      wound healing, and inflammation. There is enormous heterogeneity in macrophage
      phenotype, from 'classically' activated macrophages that have important roles in
      inflammation and innate immunity, to 'alternative' macrophage activation that is
      associated with wound healing, angiogenesis, and immune-suppression. Most, if not
      all, solid tumors have a significant macrophage population, clinical and
      experimental evidence suggests tumor-associated macrophages (TAM) are linked with
      tumor progression. The trophic functions of TAM are associated with increased
      angiogenesis, malignant cell invasion, and metastasis. NF-kappaB is s central
      regulator of inflammation and NF-kappaB activation particularly in TAM is linked
      with promotion of carcinogenesis in various experimental models of inflammation
      associated cancer. NF-kappaB activation in TAM has, therefore, been suggested to
      represent a molecular link between inflammation and cancer. However, TAM
      frequently display an anti-inflammatory phenotype linked with immune-suppression
      that is not easily reconciled with a pro-inflammatory function for NF-kappaB in
      TAM. Here, I review the form and function of TAM and discuss the role of NF
      kappaB activation in TAM in carcinogenesis.

PMID- 21080152
TI  - From Toll-like receptors to the toll house of type 1 diabetes mellitus.

PMID- 21080153
TI  - Detectability of the Eurasian otter by standard surveys: an approach using
      marking intensity to estimate false negative rates.
AB  - False negative detections may bias the surveys for rare species and reduce the
      reliability of models based on the proportion of occupied patches. We assessed
      the detectability of the Eurasian otter Lutra lutra through the standard survey
      method by analysing the detection history of 28 sampling stretches surveyed
      monthly between March 2001 and January 2003. Each survey negative for otter
      spraints was considered as a false negative if the otter had been recorded in the
      previous and/or following month (respectively, cFN and FN). Otter marking
      intensity (MI) (MI=N degrees  of spraints per kilometre) was calculated and
      assumed to represent an index of its relative abundance. Spraints were found in
      81.7% of all surveys. Yearly MI ranged from 1.02 to 101.4 spraints per kilometre.
      In 2002, mean MI was significantly lower than in the previous year, while no
      clear seasonal trend could be outlined. The minimum number of surveys required to
      establish the occurrence of the otter, as estimated by a probability model, was
      2.6 and was inversely related to MI. For a sub-sample of 18 sampling stretches,
      the relation between the frequency of both cFN and FN and five variables of
      potential interest for otters was tested by means of stepwise linear multiple
      regressions, yielding two highly significant models, which both included only MI
      as the explanatory variable. The frequency of both FN and cFN was correlated to
      MI and the resulting equations used to assess the percentage of surveys positive
      for otters in both years. After the correction for non-detections, otter site
      occupancy did not vary between the 2 years, except for one river when applying
      the more conservative estimate of false negatives (cFN). Multiple visits and the
      assessing of MI should become standard components of otter surveys. This approach
      has broad applicability and may be applied to assess the large-scale distribution
      of other rare or elusive mammalian carnivores.

PMID- 21080154
TI  - Sticky snack for sengis: the Cape rock elephant-shrew, Elephantulus edwardii
      (Macroscelidea), as a pollinator of the Pagoda lily, Whiteheadia bifolia
      (Hyacinthaceae).
AB  - Following the recent discovery of rodent pollination in the Pagoda lily,
      Whiteheadia bifolia (Hyacinthaceae) in South Africa, now the Cape rock elephant
      shrew, Elephantulus edwardii (Macroscelidea, Afrotheria) is reported as an
      additional pollinator. Elephant-shrews, live-trapped near W. bifolia plants, were
      released in two terraria, containing the plants. The animals licked nectar with
      their long and slender tongues while being dusted with pollen and touching the
      stigmas of the flowers with their long and flexible noses. The captured elephant
      shrews had W. bifolia pollen in their faeces, likely as a result of grooming
      their fur as they visited the flowers without eating or destroying them. The
      animals mostly preferred nectar over other food. This is the first record of
      pollination and nectar consumption in the primarily insectivorous E. edwardii,
      contributing to the very sparse knowledge about the behaviour of this unique
      clade of African mammals, as well as pollination by small mammals.

PMID- 21080155
TI  - Towards a sensible comprehension of severe community-acquired pneumonia.
AB  - Four different rules have been suggested and validated for intensive care unit
      (ICU) admission for community-acquired pneumonia: modified American Thoracic
      Society (ATS) rule, Infectious Diseases Society of America (IDSA)/ATS rule,
      Espana rule, and SMART-COP. Their performance varies, with sensitivity of around
      70% and specificity of around 80-90%. Only negative predictive values are
      consistently high. Critical methodological issues include the appropriate
      reference for derivation, the populations studied, the variables included, and
      the time course of pneumonia. Severe community-acquired pneumonia (SCAP) may
      evolve because of acute respiratory failure or/and severe sepsis/septic shock.
      Pneumonia-related complications and decompensated comorbidities may be additional
      or independent reasons for a severe course. All variables included in predictive
      rules relate to the two principal reasons for SCAP. However, taken as major
      criteria, they are of little value for clinical assessment. Instead, a limited
      set of minor criteria reflecting severity seems appropriate. However, predictive
      rules may not meet principal needs of severity assessment because of failure in
      sensitivity, ignorance of the potential contribution of complications or
      decompensated comorbidity to pneumonia severity, and poor sensitivity for the
      lower extreme in the spectrum of severe pneumonia, i.e., patients at risk of
      SCAP. We therefore advocate an approach that refers to the evaluation of the need
      for intensified treatment rather than ICU, based on a set of minor criteria and
      sensitive to the dynamic nature of pneumonia. Intensified treatment such as
      monitoring and treatment of acute respiratory failure or/and severe sepsis/septic
      shock is thought to improve management and possibly outcomes by setting the focus
      on both patients with severity criteria at admission and those at risk for SCAP.

PMID- 21080156
TI  - Size distribution and buoyant density of Burkholderia pseudomallei.
AB  - The size and density of microbial cells determine the time that pathogens can
      remain airborne and thus, their potential to infect by the respiratory route. We
      determined the density and size distribution of Burkholderia pseudomallei cells
      in comparison with other Burkholderia species, including B. mallei and B.
      thailandensis, all prepared and analyzed under similar conditions. The observed
      size distribution and densities of several bacterial strains indicates that
      aerosolized particles consisting of one or of a few B. pseudomallei cells should
      be efficiently retained in the lungs, highlighting the risk of transmission of
      melioidosis by the respiratory route when the pathogen is present in fluids from
      infected patients or aerosolized from the environment.

PMID- 21080157
TI  - Relative finger position influences whether you can localize tactile stimuli.
AB  - To investigate whether the relative positions of the fingers influence tactile
      localization, participants were asked to localize tactile stimuli applied to
      their fingertips. We measured the location and rate of errors for three finger
      configurations: fingers stretched out and together so that they are touching each
      other, fingers stretched out and spread apart maximally and fingers stretched out
      with the two hands on top of each other so that the fingers are interwoven. When
      the fingers contact each other, it is likely that the error rate to the adjacent
      fingers will be higher than when the fingers are spread apart. In particular, we
      reasoned that localization would probably improve when the fingers are spread. We
      aimed at assessing whether such adjacency was measured in external coordinates
      (taking proprioception into account) or on the body (in skin coordinates). The
      results confirmed that the error rate was lower when the fingers were spread.
      However, there was no decrease in error rate to neighbouring fingertips in the
      fingers spread condition in comparison with the fingers together condition. In an
      additional experiment, we showed that the lower error rate when the fingers were
      spread was not related to the continuous tactile input from the neighbouring
      fingers when the fingers were together. The current results suggest that
      information from proprioception is taken into account in perceiving the location
      of a stimulus on one of the fingertips.

PMID- 21080158
TI  - Diffusion-weighted magnetic resonance imaging of symptomatic nerve root of
      patients with lumbar disk herniation.
AB  - INTRODUCTION: Diffusion-weighted imaging (DWI) can provide valuable structural
      information that may be useful for evaluating pathological changes of the lumbar
      nerve root. Diffusion-weighted magnetic resonance (MR) neurography has recently
      been introduced as an alternative way to visualize nerves, but to date,
      quantitative DWI and MR neurography have not been applied to evaluate the
      pathology of lumbar nerve roots. METHODS: Our purpose was to visualize lumbar
      nerve roots and to analyze their morphology by MR neurography, and to measure the
      apparent diffusion coefficient (ADC) of lumbar nerve roots compressed by
      herniated disks using 1.5-T MR imaging. Ten consecutive patients (median age,
      48.0 and range, 20-72 years) with monoradicular symptoms caused by a lumbar
      herniated disk and 14 healthy volunteers were studied. Regions of interests were
      placed on the lumbar roots at dorsal root ganglia (DRG) and distal spinal nerves
      on DWI to quantify mean ADC values. The spinal nerve roots were also visualized
      by MR neurography. RESULTS: In the patients, mean ADC values were significantly
      greater in the compressed DRG and distal spinal nerves than in intact nerves. MR
      neurography also showed abnormalities such as nerve swelling at and below the
      compression in the symptomatic nerve root. Increased ADC values were considered
      to be because of edema and Wallerian degeneration of compressed nerve roots.
      CONCLUSION: DWI is a potential tool for analysis of the pathophysiology of lumbar
      nerve roots compressed by herniated disks.

PMID- 21080159
TI  - Pineal parenchymal tumor of intermediate differentiation: imaging spectrum of an
      unusual tumor in 11 cases.
AB  - INTRODUCTION: Pineal parenchymal tumor of intermediate differentiation (PPTID)
      was recognized in the 2007 World Health Organization (WHO) classification as a
      new pineal parenchymal neoplasm, intermediate in malignancy (WHO grade II or III)
      between pineocytoma (grade I) and pineoblastoma (grade IV). The imaging spectrum
      of this new tumor has not been previously delineated. We describe the imaging
      spectrum in 11 pathologically proven PPTIDs and identify findings that may
      suggest the preoperative diagnosis of this newly recognized entity. METHODS:
      Electronic medical records over the last 9 years and teaching files between the
      years 1985 and 1995 were searched for atypical pineal lesions. Additional cases
      were added from the teaching files of contributing authors. RESULTS: Imaging
      studies in nine patients (9/11) showed bulky, aggressive pineal region masses
      with local brain invasion; two patients (2/11) demonstrated circumscribed pineal
      masses. Two patients had spinal metastases at presentation. On computed
      tomography (CT), five patients had classic "exploded" calcifications
      characteristic of pineal parenchymal tumors. All tumors were heterogeneously
      hypointense on T1WIs and heterogeneously hyperintense on T2WIs. Post-contrast
      scans showed marked heterogeneous (10/11) or uniform (1/11) enhancement. Cystic
      foci were identified in eight cases. Intratumoral hemorrhage was present in one
      case. CONCLUSION: While no singular neuroimaging feature is pathognomonic of
      PPTID, these tumors are usually larger, demonstrate local invasion, and appear
      much more heterogeneous than pineocytoma. Because PPTIDs have a higher grade and
      increased potential for recurrence as compared to pineocytomas, it is important
      to consider this diagnosis as shorter follow-up, and adjuvant therapy may be
      indicated in selected cases.

PMID- 21080161
TI  - Development of the bacterial compartment along the Danube River: a continuum
      despite local influences.
AB  - Microbial food webs dominate heterotrophic food webs in large rivers with
      bacterial metabolism being a key component of carbon processing. Thus, analysis
      of bacterial population dynamics is critical to understanding patterns and
      mechanisms of material cycling and energy fluxes in large rivers. Within the
      frame of the Joint Danube Survey (JDS) 2007, the longitudinal development of the
      natural bacterial community in the Danube in terms of bacterial numbers,
      morphotype composition, and heterotrophic production of the suspended and
      particle-attached fractions was followed at a fine spatial resolution of
      approximately 30 km for the first time in such a large river along a 2,600-km
      stretch. Twenty-one major tributaries and branches were also included. This
      allowed us to investigate whether bacterial standing stock and production undergo
      continuous, linear changes or whether discontinuities and local processes like
      the merging of tributaries or the potential impact of sewage input drive the
      bacterial population in the Danube. The presented investigation revealed
      surprising continuous patterns of changes of bacterial parameters along the
      Danube River. Despite the presence of impoundments or hydropower plants, large
      municipalities, and the discharge of large tributaries, most bacterial parameters
      (standing stock, morphotype succession, and attached bacterial production)
      developed gradually, indicating that mainly broad-scale drivers and not local
      conditions shape and control the bacterial community in the midstream of this
      large river. As most important broad-scale drivers, nutrients (inorganic and
      organic) and changes in particle concentrations were identified. These data are
      also in remarkable accordance with the patterns of changes of the genetic
      bacterial community composition, observed during the first JDS (2001) 6 years
      before. In contrast, bacterial activity did not follow a continuous trend and was
      mainly controlled by the input of sewage from large cities in the middle section,
      leading to a bloom of phytoplankton. The observed patterns and the comparison
      between the Danube, its tributaries and other large rivers worldwide indicate
      that the bacterial community in rivers has a powerful indicator function for
      estimating the ecological status of large river ecosystems once enough
      information has been collected at various temporal and spatial scales.

PMID- 21080160
TI  - Delayed thrombosis of a complex fusiform ICA aneurysm treated with flow reversal
      and partial occlusion: case report and brief review of possible mechanisms.
AB  - Immediate complete occlusion of complex cerebral aneurysms associated with
      perforating or major branch arteries may cause serious ischemic complications due
      to poor collateral supply. Flow reversal with concomitant proximal occlusion is
      an important therapeutic strategy in clinical practice and induces gradual
      thrombosis in the aneurysm within weeks or months, providing a time window for
      collateral progression. Herein, we report a case of delayed thrombosis of a
      complex fusiform aneurysm of the ICA following flow reversal with EC-IC bypass
      and concomitant partial coiling with parent artery occlusion. The effects of
      hemodynamic alterations on collateral circulation and intra-aneurysmal thrombosis
      are briefly discussed in the light of the literature.

PMID- 21080162
TI  - Production of serotonin by dual expression of tryptophan decarboxylase and
      tryptamine 5-hydroxylase in Escherichia coli.
AB  - A plant-specific biogenic amine, serotonin, was produced by heterologous
      expression of two key biosynthetic genes, tryptophan decarboxylase (TDC) and
      tryptamine 5-hydroxylase (T5H), in Escherichia coli. The native T5H, a cytochrome
      P450 enzyme, was unable to be functionally expressed in E. coli. Through a series
      of N-terminal deletions or additions of tagging proteins, we generated a
      functional T5H enzyme construct (GST?37T5H) in which glutathione S transferase
      (GST) was translationally fused with the N-terminal 37 amino acid deleted T5H.
      Dual expression of GST?37T5H and TDC using a pCOLADuet-1 E. coli vector produced
      serotonin at concentrations of approximately 24 mg l-1 in the culture medium and
      4 mg l-1 in the cells. An optimum temperature of approximately 20  degrees C was
      required to achieve peak serotonin production in E. coli because the low
      induction temperature gave rise to the highest soluble expression of GST?37T5H.

PMID- 21080163
TI  - Production of rhamnolipids in solid-state cultivation using a mixture of
      sugarcane bagasse and corn bran supplemented with glycerol and soybean oil.
AB  - Rhamnolipid biosurfactants are attracting attention due to their low toxicity,
      high biodegradability, and good ecological acceptability. However, production in
      submerged culture is made difficult by severe foaming problems. Solid-state
      cultivation (SSC) is a promising alternative production method. In the current
      work, we report the optimization of rhamnolipid production by Pseudomonas
      aeruginosa UFPEDA 614 on a solid substrate containing sugarcane bagasse and corn
      bran. The best rhamnolipid production, 45 g/l of impregnating solution used, was
      obtained with a 50:50 (m/m) mixture of sugarcane bagasse and corn bran
      supplemented with an impregnating solution containing 6% (v/v) of each of
      glycerol and soybean oil. This level is comparable with those of previous studies
      undertaken in solid-state cultivation; the composition of the biosurfactant is
      similar, but our medium is cheaper. Our work therefore provides a suitable basis
      for future studies of the development of an SSC-based process for rhamnolipid
      production.

PMID- 21080165
TI  - CDR2 antigen and Yo antibodies.
AB  - Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo
      antibodies that are directed against human cerebellar degeneration-related
      protein 2 (CDR2). Such antibodies may also be found in ovarian cancer patients
      without PCD. We studied if there was an association between Yo antibody
      production and differences in CDR2 cDNA sequence, mRNA or CDR2 expression in
      ovarian cancers. We found similar CDR2 cDNA sequence, mRNA and protein levels in
      primary ovarian cancers, with or without associated Yo antibodies. CDR2 was also
      present in other cancers, as well as in normal ovary tissue. The results suggest
      that Yo antibodies are not only related to the expression of CDR2 alone, but also
      to immune dysregulation.

PMID- 21080166
TI  - Minimal information about T cell assays: the process of reaching the community of
      T cell immunologists in cancer and beyond.
AB  - Many assays to evaluate the nature, breadth, and quality of antigen-specific T
      cell responses are currently applied in human medicine. In most cases, assay
      related protocols are developed on an individual laboratory basis, resulting in a
      large number of different protocols being applied worldwide. Together with the
      inherent complexity of cellular assays, this leads to unnecessary limitations in
      the ability to compare results generated across institutions. Over the past few
      years a number of critical assay parameters have been identified which influence
      test performance irrespective of protocol, material, and reagents used.
      Describing these critical factors as an integral part of any published report
      will both facilitate the comparison of data generated across institutions and
      lead to improvements in the assays themselves. To this end, the Minimal
      Information About T Cell Assays (MIATA) project was initiated. The objective of
      MIATA is to achieve a broad consensus on which T cell assay parameters should be
      reported in scientific publications and to propose a mechanism for reporting
      these in a systematic manner. To add maximum value for the scientific community,
      a step-wise, open, and field-spanning approach has been taken to achieve
      technical precision, user-friendliness, adequate incorporation of concerns, and
      high acceptance among peers. Here, we describe the past, present, and future
      perspectives of the MIATA project. We suggest that the approach taken can be
      generically applied to projects in which a broad consensus has to be reached
      among scientists working in fragmented fields, such as immunology. An additional
      objective of this undertaking is to engage the broader scientific community to
      comment on MIATA and to become an active participant in the project.

PMID- 21080167
TI  - A long peptide from MELOE-1 contains multiple HLA class II T cell epitopes in
      addition to the HLA-A*0201 epitope: an attractive candidate for melanoma
      vaccination.
AB  - CD4(+) T cells contribute importantly to the antitumor T cell response, and thus,
      long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines.
      We have previously identified an overexpressed antigen in melanoma, MELOE-1,
      presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context. A
      T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects
      and melanoma patients and the adjuvant injection of TIL containing MELOE-1
      specific CD8(+) T cells to melanoma patients was shown to be beneficial. In this
      study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201
      epitope. Stimulation of PBMC from healthy subjects with MELOE-1(26-46) revealed
      CD4 responses in multiple HLA contexts and by cloning responsive CD4(+) T cells,
      we identified one HLA-DRbeta1*1101-restricted and one HLA-DQbeta1*0603-restricted
      epitope. We showed that the two epitopes could be efficiently presented to CD4(+)
      T cells by MELOE-1-loaded dendritic cells but not by MELOE-1+ melanoma cell
      lines. Finally, we showed that the long peptide MELOE-1(22-46), containing the
      two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently
      processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making
      it a potential candidate for melanoma vaccination.

PMID- 21080168
TI  - A prospective study to assess the predictive value for hereditary spherocytosis
      using five laboratory tests (cryohemolysis test, eosin-5'-maleimide flow
      cytometry, osmotic fragility test, autohemolysis test, and SDS-PAGE) on 50
      hereditary spherocytosis families in Argentina.
AB  - This prospective study was carried out to assess the usefulness of five
      laboratory tests in the diagnosis of hereditary spherocytosis (HS), based on the
      correlation of erythrocyte membrane protein defects with clinical and laboratory
      features, and also to determine the membrane protein deficiencies detected in
      Argentina. Of 116 patients and their family members tested, 62 of them were
      diagnosed to have HS. The specificity of cryohemolysis (CH) test was 95.2%, and
      its cut-off value to distinguish HS from normal was 2.8%. For flow cytometry, cut
      off points of 17% for mean channel fluorescence (MCF) decrease and 14%
      coefficient of variation (CV) increase showed 95.9% and 92.2% specificity,
      respectively. Both tests showed the highest percentages of positive results for
      diagnosis. Either CH or flow cytometry was positive in 93.5% of patients. In
      eight patients, flow cytometry was positive only through CV increase. Protein
      defects were detected in 72.3% of patients; ankyrin and spectrin were the most
      frequently found deficiencies. The CV of the fluorescence showed significantly
      higher increases in moderate and severe anemia than in mild anemia (p = 0.003).
      Severity of anemia showed no other correlation with tests results, type of
      deficient protein, inheritance pattern, or neonatal jaundice. CH and flow
      cytometry are easy methods with the highest diagnostic accuracy. Simultaneous
      reading of mean channel fluorescence (MCF) decrease and CV increase improve
      diagnostic usefulness of flow cytometry. This test seems to be a reliable
      predictor of severity. The type of detected protein deficiency has no predictive
      value for outcome. Predominant ankyrin and spectrin deficiencies agree with
      reports from other Latin American countries.

PMID- 21080169
TI  - Rigorous conditions for food-web intervality in high-dimensional trophic niche
      spaces.
AB  - Food webs represent trophic (feeding) interactions in ecosystems. Since the late
      1970s, it has been recognized that food-webs have a surprisingly close
      relationship to interval graphs. One interpretation of food-web intervality is
      that trophic niche space is low-dimensional, meaning that the trophic character
      of a species can be expressed by a single or at most a few quantitative traits.
      In a companion paper we demonstrated, by simulating a minimal food-web model,
      that food webs are also expected to be interval when niche-space is high
      dimensional. Here we characterize the fundamental mechanisms underlying this
      phenomenon by proving a set of rigorous conditions for food-web intervality in
      high-dimensional niche spaces. Our results apply to a large class of food-web
      models, including the special case previously studied numerically.

PMID- 21080170
TI  - Periodicity and synchronization in blood-stage malaria infection.
AB  - Malaria fever is highly periodic and is associated with the parasite replication
      cycles in red blood cells. The existence of periodicity in malaria infection
      demonstrates that parasite replication in different red blood cells is
      synchronized. In this article, rigorous mathematical analysis of an age
      structured human malaria model of infected red blood cells (Rouzine and McKenzie,
      Proc Natl Acad Sci USA 100:3473-3478, 2003) is provided and the synchronization
      of Plasmodium falciparum erythrocytic stages is investigated. By using the
      replication rate as the bifurcation parameter, the existence of Hopf bifurcation
      in the age-structured malaria infection model is obtained. Numerical simulations
      indicate that synchronization with regular periodic oscillations (of period 48 h)
      occurs when the replication rate increases. Therefore, Kwiatkowski and Nowak's
      observation (Proc Natl Acad Sci USA 88:5111-5113, 1991) that synchronization
      could be generated at modest replication rates is confirmed.

PMID- 21080171
TI  - Chest computed tomography using iterative reconstruction vs filtered back
      projection (Part 2): image quality of low-dose CT examinations in 80 patients.
AB  - PURPOSE: To evaluate the image quality of an iterative reconstruction algorithm
      (IRIS) in low-dose chest CT in comparison with standard-dose filtered back
      projection (FBP) CT. MATERIALS AND METHODS: Eighty consecutive patients referred
      for a follow-up chest CT examination of the chest, underwent a low-dose CT
      examination (Group 2) in similar technical conditions to those of the initial
      examination, (Group 1) except for the milliamperage selection and the replacement
      of regular FBP reconstruction by iterative reconstructions using three (Group 2a)
      and five iterations (Group 2b). RESULTS: Despite a mean decrease of 35.5% in the
      dose-length-product, there was no statistically significant difference between
      Group 2a and Group 1 in the objective noise, signal-to-noise (SNR) and contrast
      to-noise (CNR) ratios and distribution of the overall image quality scores.
      Compared to Group 1, objective image noise in Group 2b was significantly reduced
      with increased SNR and CNR and a trend towards improved image quality.
      CONCLUSION: Iterative reconstructions using three iterations provide similar
      image quality compared with the conventionally used FBP reconstruction at 35%
      less dose, thus enabling dose reduction without loss of diagnostic information.
      According to our preliminary results, even higher dose reductions than 35% may be
      feasible by using more than three iterations.

PMID- 21080172
TI  - Surgical treatment of huge congenital extracranial immature teratoma: a case
      report.
AB  - Congenital cranial teratomas are usually characterized by complete loss of the
      normal intracranial architecture. In the majority of reports, the tumors are
      associated with stillbirth, perinatal death, or significant morbidity after
      surgical resection. The few reported attempts at total or subtotal tumor
      resection have had poor outcomes, although there are rare reports of prolonged
      survival up to 3.5 years following resection of smaller tumors. Neonatal
      teratomas are rarely located in the scalp. In the literature, there were only a
      few patients who underwent surgery during the neonatal period with a good
      outcome; however, all such patients survived. In this paper, we present a
      neonatal case of huge congenital extracranial immature teratoma on the scalp
      extending to the orbita, ears, and brain. Examination of the patient revealed a
      large craniofacial mass and head circumference that was bigger than normal; there
      were no other neurological deficits. Computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed a multiloculated, heterogeneous cystic mass that
      was larger than the patient's head, displacing and distorting anatomical
      structures. MRI showed mass with calcifications, soft tissue, fat, and fluid
      components. There was deformity and remodeling of the adjacent calvaria. A total
      surgical excision was performed and histopathological examination showed immature
      teratoma. The patient's early postoperative course was uneventful. Postoperative
      CT and MRI were normal. To date, the patient has survived for 6 months without
      neurological deficit. We conclude that acceptable functional outcomes in the
      context of massive congenital craniofacial teratomas can be achieved by early
      radical resection.

PMID- 21080173
TI  - Amniotic band syndrome with tethering of the spinal cord: a case-based update.
AB  - BACKGROUND: Amniotic band syndrome consists of a wide spectrum of clinical
      manifestations attributed to entanglement and disruption of different developing
      parts of the embryo. Multiple asymmetric encephalocele and anencephaly have
      previously been reported with amniotic band syndrome. Tethering of the spinal
      cord secondary to amniotic band constriction is exceedingly rare, and this is the
      second reported case in the literature. CASE REPORT: We present a case of
      amniotic band resulting in tethering of spinal cord. It is a rare entity, and it
      is the second reported case of amniotic band causing tethering of the spinal
      cord. Standard operative approach was used to untether the cord. The child made
      good post-op recovery without any neurological deterioration. A review of the
      literature and causative theories is discussed. CONCLUSIONS: Neural tube defects
      involving head and spine are thought to result from adhesions between
      craniofacial structures and chorionic wall or compression forces by amniotic
      bands. Tethering of the thoracic spinal cord with amniotic band is an exceedingly
      rare occurrence. It is a rare entity, but it can be treated with a conventional
      approach with a favourable outcome.

PMID- 21080174
TI  - Cognitive functions correlate with diffusion tensor imaging metrics in patients
      with spina bifida cystica.
AB  - PURPOSE: Spina bifida cystica (SBC) is a group of neurodevelopmental defects
      caused by improper neural tube closure, which may be responsible for deficits in
      cognitive functions. The purpose of this study was to examine changes in normal
      appearing deep gray and white matter brain regions in SBC patients compared with
      controls through diffusion tensor imaging (DTI) and correlate these changes with
      neuropsychometric tests. METHODS: Conventional magnetic resonance imaging and
      neuropsychometric tests were performed on 13 patients and ten controls. DTI
      derived fractional anisotropy (FA) and mean diffusivity (MD) were quantified in
      different brain regions in controls and patients. RESULTS: Significantly
      decreased FA was observed in caudate nuclei, putamen, genu, splenium, and
      increased FA was found in middle cerebellar peduncle (MCP) in patients compared
      with controls. We observed significantly increased MD in genu and splenium.
      However, increased MD was found in fornix of patients compared with controls.
      Majority of neuropsychological tests were found to be significantly impaired and
      some of these showed significant correlation with DTI metrics in genu, splenium,
      and MCP in these patients. CONCLUSIONS: We conclude that DTI metrics are
      significantly abnormal in deep gray matter nuclei, genu, splenium, and MCP in SBC
      patients and may provide microstructural basis for neuropsychological
      abnormalities in these patients.

PMID- 21080175
TI  - Reaction to silk suture in children undergoing neurosurgery: case reports and
      review of the literature.

PMID- 21080176
TI  - Learning disorders in children with epilepsy.
AB  - INTRODUCTION: Learning Disorders (LD) are defined as disorders that interfere
      with academic performance or with daily activities that require reading, writing
      or mathematical skills in subjects with a normal intelligence quotient (IQ). The
      prevalence of LD in the general population has been found to be 2-10%, and
      reading disorders are the most frequent subtype. Epilepsy is one of the most
      common serious neurological disorders in childhood. LD are more common in
      children with epilepsy than in the general population. As a consequence, the risk
      of cognitive impairment in children with epilepsy is high, and a review of the
      literature needs to be fully presented. METHODS: Narrative review including
      articles regarding LD in children with various epileptic syndromes published in
      the international medical literature. RESULTS: LD are more frequent among
      children with epilepsy. The etiology is multifactorial, being affected by the
      type of epileptic syndrome, the age of onset and the antiepileptic treatment
      being selected. LD can be either permanent or state-dependent. Each category has
      different treatment protocols and prognosis. CONCLUSIONS: Despite the fact that
      the findings of the studies discussed in our article support the evidence that
      epilepsy in childhood impairs the cognitive function, we should not underestimate
      the role of demographic and psychosocial factors on academic performance of
      children with epilepsy. Despite the high prevalence of LD, a healthy family and
      school environment can help reduce its impact on the patient's quality of life.

PMID- 21080178
TI  - Absence of IDH mutation identifies a novel radiologic and molecular subtype of
      WHO grade II gliomas with dismal prognosis.
AB  - The phenotypic heterogeneity of low-grade gliomas (LGGs) is still inconsistently
      explained by known molecular abnormalities in patients treated according to the
      present standards of care. IDH1 codon 132 and IDH2 codon 172 sequencing was
      performed in a series of 47 LGGs and correlated with clinical presentation, MR
      imaging characteristics, genomic profile and outcome. A total of 38 IDH1
      mutations at codon 132 and 2 IDH2 mutations at codon 172 were found, including 35
      R132H (87.5%), 2 R132C (5.0%), 1 R132S (2.5%) and 2 R172 M (5%). The IDH
      mutations were significantly associated with 1p19q deleted genotype (P = 0.031)
      and p53 expression (P = 0.014). The presence (vs. absence) of IDH mutations was
      associated with a better outcome (5-year survival rate, 93% vs. 51%,
      respectively, P = 0.000001). After adjustment for age, tumor location and size,
      radiologic infiltration pattern and extent of surgery, multivariate analysis
      confirmed that IDH mutations was an independent favorable prognostic factor
      (hazard ratio = 40.9; 95% CI, 2.89-578.49, P = 0.006). Furthermore, we showed
      that patients with IDH-nonmutated tumors were significantly older (P = 0.020) and
      that these tumors involved significantly more frequently the insula (P = 0.004),
      were larger in size (>6 cm, P = 0.047), displayed an infiltrative pattern on MRI
      (P = 0.007) and were all p53 negative with no 1p19q deletion (P < 10-6). The
      absence of IDH mutations in LGGs identifies a novel entity of LGGs with
      distinctive location, infiltrative behavior, specific molecular alterations, and
      dismal outcome. These findings could significantly modify the LGG classification
      and may represent a new tool to guide patient-tailored therapy.

PMID- 21080177
TI  - Protective mechanism of glutamine on the expression of proliferating cell nuclear
      antigen after cisplatin-induced intestinal mucosal injury.
AB  - BACKGROUND: Glutamine prevents the intestinal mucosal injury induced by
      chemotherapy. However, the mechanism has not yet been elucidated. Proliferating
      cell nuclear antigen (PCNA) is expressed in the nuclei of cells during the DNA
      synthesis phase of the cell cycle, and PCNA is also involved in the DNA damage
      tolerance pathway known as post-replication repair. We hypothesized that
      glutamine supplementation might stimulate the intestinal epithelial cell cycle
      interruption induced by chemotherapy. The effect of supplemental glutamine after
      cisplatin-induced intestinal mucosal injury on the expression of PCNA was
      investigated. MATERIALS AND METHODS: The male Wister rats were divided into three
      groups; a control group (control n = 5), which received standard rat diet; the
      Cis group (cisplatin 6 mg/kg i.p., n = 5), and the Cis + Gln group [cisplatin +
      Ala-Glutamine (0.5 g/day * 3 days p.o., n = 5)]. After 1, 3, and 7 days of
      chemotherapy, PCNA, and glutamine transporter (ASCT2) expression in the small
      intestine (jejunum and ileum) was investigated. RESULTS: The expression of PCNA
      in the crypt of the small intestine (jejunum and ileum) decreased after
      chemotherapy, while the expression strongly increased by glutamine
      administration, even if it was after chemotherapy. On day 1, both the mRNA
      expression of the glutamine transporter (ASCT2) and PCNA expression in crypt
      cells were significantly increased by administration of glutamine (Cis + Gln
      group). The increased expression of ACST2 appeared earlier than in the Cis group.
      In the Cis + Gln group, the PCNA expression was normalized on day 3, and the
      expression was same as that in the control group on day 3. CONCLUSION: Glutamine
      supplementation rapidly improved the expression of PCNA after cisplatin-induced
      intestinal mucosal injury. The effects of glutamine may be due to an anti-oxidant
      effect, but the amino acid might also attenuate the initial mucosal injury and
      improve intestinal cell turnover.

PMID- 21080179
TI  - Parallel fiber counts and parallel fiber integrated density are similar in
      essential tremor cases and controls.

PMID- 21080180
TI  - Diversity of prion diseases: (no) strains attached?

PMID- 21080181
TI  - Genome-wide comparison of paired fresh frozen and formalin-fixed paraffin
      embedded gliomas by custom BAC and oligonucleotide array comparative genomic
      hybridization: facilitating analysis of archival gliomas.
AB  - Array comparative genomic hybridization (aCGH) is a powerful tool for detecting
      DNA copy number alterations (CNA). Because diffuse malignant gliomas are often
      sampled by small biopsies, formalin-fixed paraffin-embedded (FFPE) blocks are
      often the only tissue available for genetic analysis; FFPE tissues are also
      needed to study the intratumoral heterogeneity that characterizes these
      neoplasms. In this paper, we present a combination of evaluations and technical
      advances that provide strong support for the ready use of oligonucleotide aCGH on
      FFPE diffuse gliomas. We first compared aCGH using bacterial artificial
      chromosome (BAC) arrays in 45 paired frozen and FFPE gliomas, and demonstrate a
      high concordance rate between FFPE and frozen DNA in an individual clone-level
      analysis of sensitivity and specificity, assuring that under certain array
      conditions, frozen and FFPE DNA can perform nearly identically. However, because
      oligonucleotide arrays offer advantages to BAC arrays in genomic coverage and
      practical availability, we next developed a method of labeling DNA from FFPE
      tissue that allows efficient hybridization to oligonucleotide arrays. To
      demonstrate utility in FFPE tissues, we applied this approach to biphasic
      anaplastic oligoastrocytomas and demonstrate CNA differences between DNA obtained
      from the two components. Therefore, BAC and oligonucleotide aCGH can be sensitive
      and specific tools for detecting CNAs in FFPE DNA, and novel labeling techniques
      enable the routine use of oligonucleotide arrays for FFPE DNA. In combination,
      these advances should facilitate genome-wide analysis of rare, small and/or
      histologically heterogeneous gliomas from FFPE tissues.

PMID- 21080182
TI  - Implementing a collaborative protocol in a sepsis intervention program: lessons
      learned.
AB  - The objective of this prospective cohort study was to see the effect of the
      implementation of a Sepsis Intervention Program on the standard processes of
      patient care using a collaborative approach between the Emergency Department (ED)
      and Medical Intensive Care Unit (MICU). This was performed in a large urban
      tertiary-care hospital, with no previous experience utilizing a specific
      intervention program as routine care for septic shock and which has services and
      resources commonly available in most hospitals. The study included 106 patients
      who presented to the ED with severe sepsis or septic shock. Eighty-seven of those
      patients met the inclusion criteria for complete data analysis. The ED and MICU
      staff underwent a 3-month training period followed by implementation of a
      protocol for sepsis intervention program over 6 months. In the first 6 months of
      the program's implementation, 106 patients were admitted to the ED with severe
      sepsis and septic shock. During this time, the ED attempted to initiate the
      sepsis intervention protocol in 76% of the 87 septic patients who met the
      inclusion criteria. This was assessed by documentation of a central venous
      catheter insertion for continuous SvO(2) monitoring in a patient with sepsis or
      septic shock. However, only 48% of the eligible patients completed the early goal
      directed therapy (EGDT) protocol. Our data showed that the in-hospital mortality
      rate was 30.5% for the 87 septic shock patients with a mean APACHE II score of
      29. This was very similar to a landmark study of EGDT (30.5% mortality with mean
      APACHE II of 21.5). Data collected on processes of care showed improvements in
      time to fluid administration, central venous access insertion, antibiotic
      administration, vasopressor administration, and time to MICU transfer from ED
      arrival in our patients enrolled in the protocol versus those who were not.
      Further review of our performance data showed that processes of care improved
      steadily the longer the protocol was in effect, although this was not
      statistically significant. There was no improvement in secondary outcomes,
      including total length of hospital stay, MICU days, and mortality. Implementation
      of a sepsis intervention program as a standard of care in a typical hospital
      protocol leads to improvements in processes of care. However, despite a
      collaborative approach, the sepsis intervention program was underutilized with
      only 48% of the patients completing the sepsis intervention protocol.

PMID- 21080184
TI  - Levodopa: back to the future.

PMID- 21080183
TI  - Oxygen uptake, ventilation, and symptoms during low-frequency versus high
      frequency NMES in COPD: a pilot study.
AB  - Transcutaneous neuromuscular electrical stimulation (NMES) involves the
      application of an electrical current through electrodes placed on the skin over
      the targeted muscles. During high-frequency NMES (HF-NMES), oxygen uptake, minute
      ventilation, and the degree of symptom perception (dyspnea and fatigue) have been
      shown to be acceptable in chronic obstructive pulmonary disease (COPD).
      Currently, oxygen uptake and ventilation load have never been assessed during low
      frequency NMES (LF-NMES) of the lower-limb muscles. The purpose of this study was
      to compare prospectively oxygen uptake, ventilation, and symptom perception
      during a single session of LF-NMES versus a single session of HF-NMES of
      quadriceps muscles in patients with COPD. In 17 COPD patients (mean FEV(1) = 45%
      predicted, mean body mass index = 26.2 kg/m(2)), peak exercise capacity,
      functional exercise capacity, and the Medical Research Council dyspnea grade were
      evaluated. In addition, oxygen uptake, minute ventilation, heart rate, and Borg
      symptom scores were assessed during one session of LF-NMES (15 Hz) and one
      session of HF-NMES (75 Hz) and compared with peak values. Mean oxygen uptake (LF
      NMES: 327 ml/min vs. HF-NMES: 315 ml/min), minute ventilation (LF-NMES: 14 L vs.
      HF-NMES: 15 L), and heart rate (LF-NMES: 86 BPM vs. HF-NMES: 83 BPM) were similar
      during both NMES frequencies. Patients used a relatively low proportion of their
      peak aerobic capacity during both NMES sessions (LF-NMES: 34% vs. HF-NMES: 33%; P
      = 0.397). In addition, symptom Borg scores for dyspnea and leg fatigue were also
      comparable. Oxygen uptake, ventilation, and symptoms of dyspnea and fatigue were
      comparable and tolerable during LF-NMES and HF-NMES in patients with COPD.
      Therefore, LF-NMES and HF-NMES may both be suitable rehabilitative modalities to
      be used in severely dyspneic patients with lower-limb muscle dysfunction.

PMID- 21080185
TI  - A brief history of levodopa.
AB  - This article highlights some landmarks in the history of levodopa, beginning with
      its isolation in 1910-13 from seedlings of Vicia faba to the demonstration, in
      1961, of its "miraculous" effect in patients with Parkinson's disease (PD).
      Midway between these two time points, in 1938, L: -dopa decarboxylase was
      discovered, the enzyme that produces dopamine (DA) from levodopa. In 1957, DA was
      shown to occur in the brain, and in 1959 it was found to be enriched in the basal
      ganglia. At that time the striatal localization of DA, together with studies done
      in 1957-58 in naive and reserpine-treated animals regarding DA in the brain and
      the central effects of levodopa, suggested its possible involvement in
      "extrapyramidal control" and "reserpine parkinsonism". Following these
      discoveries, a study of (postmortem) brains of patients with basal ganglia
      disorders, including PD, was started, demonstrating, in 1960, a severe striatal
      DA deficit specifically in PD, thus furnishing a rational basis for the concept
      of "DA replacement therapy" with levodopa. Accordingly, in 1961, the first highly
      successful clinical trial with i.v. levodopa was carried out. In 1963, the DA
      deficit in the PD substantia nigra was found, indicative of a nigrostriatal DA
      pathway in the human brain, subsequently established in animal studies in 1964
      65. In 1967, the chronic, high dose oral levodopa regimen was introduced in
      treatment of PD. Besides the above highlights in the history of levodopa, the
      article also cites critical opinions of world authorities in brain research of
      the time, harmful to the cause of DA, levodopa and PD. Today, the concept of DA
      replacement with levodopa is uncontested, with levodopa being the "gold standard"
      of modern drug treatment of PD.

PMID- 21080186
TI  - Pharmacokinetics of levodopa.
AB  - This paper reviews the clinically relevant determinants of levodopa peripheral
      pharmacokinetics and main observed changes in the levodopa concentration-effect
      relationship with Parkinson's disease (PD) progression. Available clinically
      practical strategies to optimise levodopa pharmacokinetics and pharmacodynamics
      are briefly discussed. Levodopa shows particular pharmacokinetics including an
      extensive presystemic metabolism, overcome by the combined use of extracerebral
      inhibitors of the enzyme L: -amino acid decarboxylase and rapid absorption in the
      proximal small bowel by a saturable facilitated transport system shared with
      other large neutral amino acids. Drug transport from plasma to the brain is
      mediated by the same carriers operating in the intestinal mucosa. The main
      strategies to assure reproducibility of both intestinal absorption and delivery
      to the brain, and the clinical effect include standardization of levodopa dosing
      with respect to meal times and a controlled dietary protein intake. Levodopa
      plasma half-life is very short, resulting in marked plasma drug concentration
      fluctuations which are matched, as the disease progresses, to swings in the
      therapeutic response ("wearing-off" phenomena). "Wearing-off" phenomena can also
      be associated, at the more advanced disease stages, with a "negative", both
      parkinsonism-exacerbating and dyskinetic effect of levodopa at low,
      subtherapeutic plasma concentrations. Dyskinesias may also be related to high
      levodopa, excessive plasma concentrations. Recognition of the different levodopa
      toxic response patterns can be difficult on a clinical basis alone and
      simultaneous monitoring of the levodopa concentration-effect relationship may
      prove useful to disclose the underlying mechanism and in planning the correct
      management. Clinically practical strategies to optimise levodopa
      pharmacokinetics, and possibly its therapeutic response, include liquid drug
      solutions, controlled release formulations and the use of inhibitors of levodopa
      metabolism. Unfortunately, these attempts have proved so far only partly
      successful, due to the complex alterations in cerebral levodopa kinetics which
      accompany the progressive degeneration of the nigrostriatal dopaminergic system
      in PD patients.

PMID- 21080187
TI  - Has drug therapy changed the natural history of Parkinson's disease?
AB  - This narrative review examines the effects of drug therapy on the natural history
      of Parkinson's disease. In terms of modifying the underlying disease process, it
      is possible that immediate therapy, rather than deferred treatment, can have a
      positive effect on the underlying disease process. However, it is unlikely that
      drug therapy has changed mortality from the condition and there is no evidence
      that it can delay the onset of non-motor features such as dementia and falls. The
      beneficial effects of drug therapy on the motor symptoms of Parkinson's disease
      are unquestionable, but these are at the expense of short-term dopaminergic side
      effects, long-term motor complications, and impulse control disorders. Major
      questions remain regarding which initial therapeutic approach should be taken
      which may possibly be answered by the ongoing PD MED trial. The beneficial
      effects of drug therapy on the motor features of Parkinson's disease have had a
      fundamental impact on the suffering of patients. The mainstay of these therapies
      continues to be levodopa, although it is now used at lower doses than in the past
      and in combination with other drug classes.

PMID- 21080188
TI  - The clinical spectrum of levodopa-induced motor complications.
AB  - After more than 40 years of clinical use, levodopa (LD) still remains the gold
      standard for symptomatic efficacy in Parkinson's disease (PD). However, long-term
      treatment with LD is often complicated by the development of various types of
      motor response oscillations as well as drug-induced dyskinesias. These treatment
      related motor complications evolve in approximately one-third of patients after
      only 2 years of LD exposure and, once established, they are difficult to treat
      and significantly contribute to overall disability and disease burden. Although
      first described soon after the introduction of LD, the pathophysiology of motor
      complications is still not completely understood. In fact, it is most likely that
      non-physiological pulsatile stimulation of dopamine receptors, which is followed
      by various downstream alterations, plays a key role in the development of LD
      induced motor response oscillations and dyskinesias. This review outlines the
      various types of motor complications and will also address underlying mechanisms,
      treatment options, as well as impact on clinical disability and quality of life
      (QoL).

PMID- 21080189
TI  - Spectrum of addictions in Parkinson's disease: from dopamine dysregulation
      syndrome to impulse control disorders.
AB  - There is an increasing awareness that addictive disorders may occur in
      Parkinson's disease (PD), either typical substance-related addictions that are
      commonly known as dopamine dysregulation syndrome (DDS) or behavioral addictive
      syndromes, usually presenting as impulse control disorders (ICDs) that include
      pathological gambling, hypersexuality, compulsive eating and buying. DDS is
      characterized by the use of dopaminergic drugs in doses larger than those
      required to treat motor symptoms, despite the development of disabling
      dyskinesias. Case reporting and prospective studies have reported an association
      between ICDs and the use of dopamine-agonists (DAs) at greater doses, while DDS
      has been associated with levodopa at greater doses or short-acting DAs. Risk
      factors for addictions in PD include male sex, younger age or younger age at PD
      onset, history of substance use or bipolar disorder, and a personality profile
      characterized by impulsiveness. Functional neuroimaging studies such as
      functional MRI and PET have investigated in vivo the neurobiological basis of
      these pathologic behaviors. The management for clinically significant ICD
      symptoms should consist of modifications to dopamine replacement therapy (DRT),
      particularly DAs, which is usually associated with an improvement of ICDs,
      whereas there is no empiric evidence supporting the use of psychiatric drugs in
      ICDs in PD. Management of DDS is not easy, mainly because balancing the drugs in
      the long term could represent a difficult problem. Hypomanic and psychotic
      episodes are best managed with a reduction of DRT performed in hospital also by
      using atypical antipsychotics low dose.

PMID- 21080191
TI  - Clinical problems in late-stage Parkinson's disease.
AB  - Advanced Parkinson's disease patients require for their care the participation of
      a multidisciplinary team. Particularly in the late stages of the disease, motor
      complications due both to medication and to progression of the disease, together
      with non-motor complications, add to the complexity of their management.
      Increasing age of the population will increase the incidence and the prevalence
      of the disease, with more patients reaching an advanced age and a more advanced
      stage of the disease, thus creating a public health problem for which we have to
      be prepared.

PMID- 21080190
TI  - The role of the long-duration response to levodopa in Parkinson's disease.
AB  - The long-duration response (LDR) to levodopa is an important component of the
      therapeutic response to the drug in Parkinson's disease (PD). Some
      characteristics are peculiar: it is independent from peripheral pharmacokinetics
      of levodopa, but it is dependent on the intervals between doses and on the size
      of each dose. Once the LDR fully develops, it is stable and maximal. After
      stopping treatment, the decay rate is inversely related to the severity of PD;
      when the LDR decreases over time, the patients present a fluctuating motor
      response. Therapeutic strategies based on the development and maintenance of the
      LDR should be sought to maximize the clinical benefit induced by levodopa and to
      avoid the appearance of motor complications.

PMID- 21080192
TI  - Soluble and controlled-release preparations of levodopa: do we really need them?
AB  - The controlled-release preparations of levodopa or newer soluble preparations of
      levodopa may improve levodopa bioavailability and tolerability and help managing
      (or even preventing) motor complications. Whether the controlled-release
      preparations or soluble preparations can really take the place of standard
      levodopa remains highly controversial, especially in patients receiving chronic
      levodopa therapy. Controlled-release formulations have a longer half-life and
      provide more stable plasma levels than standard levodopa. In de novo parkinsonian
      patients, controlled-release levodopa and standard levodopa are equally
      efficacious, and carry similar motor complication rates. In patients with
      advanced disease, whether motor fluctuations respond better to controlled release
      than to standard oral levodopa remains unclear. In selected parkinsonian
      patients, single bedtime doses of controlled-release levodopa may improve sleep
      and nocturnal disability. The poor solubility of levodopa may be overcome by
      soluble formulations that achieve maximal absorption. A levodopa formulation that
      guarantees faster and more reliable absorption would be especially useful in the
      clinical treatment of Parkinson's disease patients experiencing "no-on" or
      "delayed-on" phenomena. However, further studies with these new formulations are
      needed to understand if they offer better benefit to parkinsonian patients. New
      dual formulations incorporating both a faster absorption and an increased half
      life than standard levodopa are currently under study.

PMID- 21080194
TI  - Continuous dopaminergic delivery in Parkinson's disease.
AB  - Motor fluctuations and dyskinesias occur in the majority of patients with
      Parkinson's disease (PD) and are likely to result from changes in dopamine
      production, storage and release, occurring as consequences of the nigrostriatal
      degenerative process. All studies comparing levodopa versus dopamine agonist
      early therapy indicate that initiation with agonists is associated with a reduced
      risk of motor complications -in particular, dyskinesias- possibly because
      agonists' longer half-lives provide continuous dopaminergic delivery. In advanced
      PD patients, switching from a pulsatile to continuous dopaminergic delivery may
      widen patients' therapeutic window. Currently, this can be accomplished only with
      subcutaneous apomorphine or duodenal levodopa infusions. Apomorphine is a highly
      soluble agonist whose effect is similar to dopamine. Conversely, replacing whole
      oral therapy with levodopa infusion bypasses gastric emptying and avoids peaks
      and troughs in plasma by releasing levodopa in the duodenum/jejunum.

PMID- 21080193
TI  - Dopaminergic therapy and subthalamic stimulation in Parkinson's disease: a review
      of 5-year reports.
AB  - The long-term efficacy and safety of deep brain stimulation (DBS) implant for
      Parkinson's disease (PD) is described in several recent papers. This procedure
      has been reported to permit a stable reduction of dopaminergic therapy
      requirements for up to 5 years, although some expectation of deterioration in non
      dopaminergic signs has been recently stated. Our aim is to perform a literature
      based review of papers available describing long-term post-operative follow-up
      after a bilateral implant for subthalamic DBS (STN-DBS). Only peer-reviewed
      published papers with a post-operative follow-up of at least 5 years were
      considered. Clinical outcome, disease progression and side effects were assessed
      at baseline and 2 (or 3 years) and 5 years after surgery. Seven papers were
      included in the review. A total of 238 patients were analyzed. STN-DBS was
      confirmed to be an effective treatment for selected patients with PD. In all
      studies, off-related motor symptoms improved dramatically, compared with pre
      implant, at 2 (or 3, according to the study) years and this result persisted at 5
      year evaluations. Antiparkinsonian drug reductions, improvements in motor
      fluctuations and dyskinesias, functional measures and the progression of
      underlying PD were also reported in all series. Some axial scores, in particular
      postural stability and speech, improved transiently. Persisting adverse effects
      included eyelid opening apraxia, weight gain, psychiatric disorders, depression,
      dysarthria, dyskinesias, and apathy. The present review of the 5-year
      observations confirms that STN-DBS is a powerful method in the management of PD,
      but its long-term effects must be thoroughly assessed.

PMID- 21080195
TI  - Evidence-based initiation of dopaminergic therapy in Parkinson's disease.
AB  - The mainstay of Parkinson's disease (PD) therapy is levodopa. The crucial
      question is when should levodopa be initiated? Levodopa provides the most potent
      motor benefit for PD, but longer term use is marked by the development of motor
      complications such as fluctuations in response and involuntary motor movements.
      Dopamine agonists reduce the risk of development of motor complications in the 5
      year term. However, side effects may change the risk-benefit of dopamine agonist
      first strategies. In the following, the evidence for levodopa and dopamine
      agonists as initial monotherapy for PD is examined.

PMID- 21080196
TI  - Resolution of total retinal detachment in Coats' disease with intravitreal
      injection of bevacizumab.

PMID- 21080197
TI  - 1000 cSt silicone oil vs heavy silicone oil as intraocular tamponade in retinal
      detachment associated to myopic macular hole.
AB  - BACKGROUND: Several surgical techniques have been described for the treatment of
      retinal detachment (RD) associated to myopic macular hole (MMH). In this
      retrospective study, the anatomical and functional outcomes of pars plana
      vitrectomy (PPV) with long-term tamponade, using either 1000 cSt silicone oil
      (SO) or heavy silicone oil (HSO), are compared. METHODS: Forty-two eyes affected
      by RD associated with MMH were included. The surgical technique involved standard
      3-port 20-gauge PPV with long-term tamponade. The patients were divided into two
      groups, according to the intraocular tamponade: SO in group 1 (n = 17), and HSO
      in group 2 (n = 25). Internal limiting membrane (ILM) removal was performed in 15
      cases of group 1 and 20 cases of group 2. Tamponade removal was performed 2 to 5
      months after primary surgery. The patients were assessed 1 week and 1 month after
      primary surgery, and then 1 week and 1 month after tamponade removal or after
      further surgery if macular redetachment had occurred. The patients were also
      visited every 2 months for at least 1 year after final tamponade removal. Follow
      up was considered closed at 1 year after final tamponade removal. RESULTS:
      Preoperative best-corrected visual acuity (BCVA), expressed as LogMar, was 2.8 +/
      0.77 for group 1 and 2.1 +/- 0.94 for group 2. At the last visit, the BCVA was
      1.41 +/- 0.96 and 1.48 +/- 0.77 for groups 1 and 2 respectively. Retinal
      reattachment was achieved with one operation in 13 eyes of group 1 (76.5%) and 18
      of group 2 (81.8%) (P = 0.69). The average number of surgery needed to achieve
      retinal attachment by patients of group 1 and 2 was respectively 1.36 +/- 0.63
      and 1.46 +/- 0.59 (P = 0.77). Five patients of group 1 and four of group 2
      developed a chronic glaucoma (P = 0.238). CONCLUSIONS: PPV with ILM peeling and
      long-term tamponade was demonstrated to be a good surgical option to treat RD due
      to MMH; SO and HSO seemed to be equally effective, although the success rates
      remained far from an ideal 100%.

PMID- 21080198
TI  - Strigolactones affect lateral root formation and root-hair elongation in
      Arabidopsis.
AB  - Strigolactones (SLs) have been proposed as a new group of plant hormones,
      inhibiting shoot branching, and as signaling molecules for plant interactions.
      Here, we present evidence for effects of SLs on root development. The analysis of
      mutants flawed in SLs synthesis or signaling suggested that the absence of SLs
      enhances lateral root formation. In accordance, roots grown in the presence of
      GR24, a synthetic bioactive SL, showed reduced number of lateral roots in WT and
      in max3-11 and max4-1 mutants, deficient in SL synthesis. The GR24-induced
      reduction in lateral roots was not apparent in the SL signaling mutant max2-1.
      Moreover, GR24 led to increased root-hair length in WT and in max3-11 and max4-1
      mutants, but not in max2-1. SLs effect on lateral root formation and root-hair
      elongation may suggest a role for SLs in the regulation of root development;
      perhaps, as a response to growth conditions.

PMID- 21080199
TI  - Relative evolutionary rates of NBS-encoding genes revealed by soybean segmental
      duplication.
AB  - It is well known that nucleotide binding site (NBS)-encoding genes are duplicate
      rich and fast-evolving genes. However, there is little information on the
      relative importance of tandem and segmental NBS duplicates and their exact
      evolutionary rates. The two rounds of large-scale duplication that have occurred
      in soybean provide a unique opportunity to investigate these issues. Comparison
      of NBS and non-NBS genes on segments of syntenic homoeologs shows that NBS
      encoding genes evolve at least 1.5-fold faster (~1.5-fold higher synonymous and
      approximately 2.3-fold higher nonsynonymous substitution rates) and lose their
      genes approximately twofold faster than the flanking non-NBS genes. Compared with
      segmental duplicates, tandem NBS duplicates are more abundant in soybean,
      suggesting that tandem duplication is the major driving force in the expansion of
      NBS genes. Notably, significant sequence exchanges along with significantly
      positive selection were detected in most tandem-duplicated NBS gene families. The
      results suggest that the rapid evolution of NBS genes may be due to the combined
      effects of diversifying selection and frequent sequence exchanges. Interestingly,
      TIR-NBS-LRR genes (TNLs) have a higher nucleotide substitution rate than non
      TNLs, indicating that these types of NBS genes may have a rather different
      evolutionary pattern. It is important to determine the exact relative
      evolutionary rates of TNL, non-TNL, and non-NBS genes in order to understand how
      fast the host plant can adjust its response to rapidly evolving pathogens in a
      coevolutionary context.

PMID- 21080200
TI  - A novel serine alkaline protease from Bacillus altitudinis GVC11 and its
      application as a dehairing agent.
AB  - A serine alkaline protease from a newly isolated alkaliphilic Bacillus
      altitudinis GVC11 was purified and characterized. The enzyme was purified to
      homogeneity by acetone precipitation, DEAE-cellulose anion exchange
      chromatography with 7.03-fold increase in specific activity and 15.25% recovery.
      The molecular weight of alkaline protease was estimated to be 28 kDa by SDS PAGE
      and activity was further assessed by zymogram analysis. The enzyme was highly
      active over a wide range of pH 8.5 to 12.5 with an optimum pH of 9.5. The optimum
      temperature of purified enzyme was 45  degrees C and Ca(2+) further increased the
      thermal stability of the enzyme. The enzyme activity was enhanced by Ca(2+) and
      Mg(2+) and inhibited by Hg(2+). The present study is the first report to examine
      and describe production of highly alkaline protease from Bacillus altitudinis and
      also its remarkable dehairing ability of goat hide in 18 h without disturbing the
      collagen and hair integrity.

PMID- 21080201
TI  - Burden of chemotherapy-induced neuropathy--a cross-sectional study.
AB  - BACKGROUND: Neuropathy is a common adverse effect of chemotherapy. However, the
      both the prevalence and the burden of this adverse effect have been poorly
      documented. The aim of the study was to assess the prevalence and discomfort
      caused by neuropathic symptoms in relation to other adverse effects of
      chemotherapy. PATIENTS AND METHODS: Between January 2002 and June 2004, we
      screened 448 patients who were treated with vinca alkaloids, taxanes or platina
      derivatives, using a simple questionnaire of neuropathic symptoms. The response
      rate was 75%. Neuropathic symptoms were reported by 258 respondents (76%), of
      whom 152 patients were eligible for the final analyses. The severity of
      neuropathy was scored using the National Cancer Institute Common Toxicity
      Criteria. RESULTS: At the screening visit, 90 patients (59%) still reported
      neuropathic symptoms. Tingling (71%), numbness (58%), impaired sensory function
      (46%) and pain in hands and feet (40%) were the most common symptoms. The median
      intensity of neuropathic symptoms was 28/100 on the visual analogue scale. Grade
      1 sensory neuropathy was found in 19 out of 90 patients (21%), grade 2 in 38
      (42%) and grade 3 in 33 (37%) patients. Grade 1 motor neuropathy was found in 28
      (31%), grade 2 in 14 (16%) and grade 3 in one patient (1%). Grade 4 sensory or
      motor neuropathy was not seen. In the whole cohort of 152 patients, fatigue
      (66%), mucositis (61%) and neuropathic symptoms (59%) were the most commonly
      reported symptoms. Every third patient (37%) with neuropathic symptoms ranked
      them as the most troublesome symptom. DISCUSSION: Neuropathy is a common and
      troublesome adverse effect of chemotherapy, even though the intensity of the
      symptoms is mild. Thus, the intensity and inconvenience does not correlate to
      each other.

PMID- 21080202
TI  - Follow-up care after breast cancer treatment: experiences and perceptions of
      service provision and provider interactions in rural Australian women.
AB  - PURPOSE: This study aims to explore and examine experiences and perceptions of
      follow-up care (medical and psychosocial) after active treatment for breast
      cancer among women living outside major Australian cities. METHOD: Twenty-five
      semi-structured telephone interviews were conducted. Participants also completed
      a brief questionnaire to collect demographic, diagnosis, and treatment
      information. Interviews were audio-recorded, transcribed, independently coded,
      and then thematically analysed. RESULTS: Themes that emerged from the interviews
      centred on patient experiences and perceptions of follow-up service provision and
      provider interactions related to medical, psychosocial, and lifestyle (e.g.,
      diet, physical activity) care. Many women perceived a marked decline in the
      quality and duration of follow-up consultations with clinicians in comparison to
      their initial treatment experiences. Several women experienced considerable
      overlap in follow-up care when multiple providers were involved resulting in
      'unnecessary' time and travel costs. Generally, women experienced limited
      availability of medical providers in rural areas, resulting in a lack of
      continuity in care, exacerbated by limited communication and coordination between
      treating health professionals. Lastly, women perceived a lack of available
      psychosocial support and resources for rural breast cancer survivors in their
      areas. CONCLUSIONS: Breast cancer survivors living outside major Australian
      cities have limited access to medical follow-up care, and psychosocial and
      lifestyle support programmes. There is a need for greater co-ordination of care
      between health professionals to improve communication and reduce patient and
      medical system burden. Finding solutions (such as eHealth options) could help to
      alleviate these barriers and improve follow-up care for rural breast cancer
      survivors.

PMID- 21080203
TI  - Assessing the variability of Brazilian Vaccinia virus isolates from a horse
      exanthematic lesion: coinfection with distinct viruses.
AB  - During the last bovine vaccinia (BV) outbreaks, several Vaccinia virus (VACV)
      strains were isolated and characterised, revealing significant polymorphisms
      between strains, even within conserved genes. Although the epidemiology of VACV
      has been studied in BV outbreaks, there is little data about the circulation of
      the Brazilian VACV isolates. This study describes the genetic and biological
      characterisation of two VACV isolates, Pelotas 1 virus (P1V) and Pelotas 2 virus
      (P2V), which were obtained concomitantly from a horse affected by severe
      cutaneous disease. Despite being isolated from the same exanthematic clinical
      sample, P1V and P2V showed differences in their plaque phenotype and in one-step
      growth curves. Moreover, P1V and P2V presented distinct virulence profiles in a
      BALB/c mouse model, as observed with other Brazilian VACV isolates. Sequencing
      and phylogenetic analysis of four different genes demonstrated that the isolates
      are segregated in different VACV clusters. Our results raise interesting
      questions about the diversity of VACV isolates in Brazil.

PMID- 21080204
TI  - Molecular and biological characterization of pepper yellow vein Mali virus
      (PepYVMV) isolates associated with pepper yellow vein disease in Burkina Faso.
AB  - Yellow vein disease (YVD) is a major problem in pepper in West Africa. Despite
      the recent implication of a begomovirus in YVD in Mali and in Burkina Faso, the
      aetiology of the disease remains unclear. Using symptomatic samples from the main
      vegetable cultivation regions in Burkina Faso, 10 full-length DNA-A-like
      begomovirus sequences were obtained, each showing 98% nucleotide identity to
      pepper yellow vein Mali virus (PepYVMV). The host range was determined after
      construction of a viral clone for agroinfection. Severe symptoms developed in
      tomato and Nicotiana benthamiana. By contrast, no symptoms developed in either
      commercial or local pepper cultivars, demonstrating that the aetiology of YVD is
      not only associated with the presence of PepYVMV.

PMID- 21080205
TI  - Molecular and statistical modeling of reduction peak potential and lipophilicity
      of platinum(IV) complexes.
AB  - We report the results of the quantitative structure-property relationship
      analysis of 31 Pt(IV) complexes, for three of which the synthesis is reported for
      the first time. The X-ray structural analysis of one complex of the series was
      performed to demonstrate that the PM6 semiempirical method satisfactorily
      reproduces key features of the geometry of the complexes investigated. Molecular
      properties extracted from such calculations were then used to construct models of
      experimental data such as electrochemical peak potentials (evaluated by cyclic
      voltammetry) and the octanol-water partition coefficient (evaluated by a reversed
      phase high performance liquid chromatography method), which are key aspects in
      the design of such Pt(IV) complexes as potential anticancer prodrugs.
      Statistically accurate models for both properties were found using combinations
      of surface areas, orbital energies, dipole moments, and atomic partial charges.
      These models could form the basis of virtual screening of potential drug
      molecules, allowing the prediction of properties, closely related to the
      antiproliferative activity of Pt(IV) complexes, directly from calculated data.

PMID- 21080206
TI  - Neural masking by sub-threshold electric stimuli: animal and computer model
      results.
AB  - Electric stimuli can prosthetically excite auditory nerve fibers to partially
      restore sensory function to individuals impaired by profound or severe hearing
      loss. While basic response properties of electrically stimulated auditory nerve
      fibers (ANF) are known, responses to complex, time-changing stimuli used
      clinically are inadequately understood. We report that forward-masker pulse
      trains can enhance and reduce ANF responsiveness to subsequent stimuli and the
      novel observation that sub-threshold (nonspike-evoking) electric trains can
      reduce responsiveness to subsequent pulse-train stimuli. The effect is observed
      in the responses of cat ANFs and shown by a computational biophysical ANF model
      that simulates rate adaptation through integration of external potassium cation
      (K) channels. Both low-threshold (i.e., Klt) and high-threshold (Kht) channels
      were simulated at each node of Ranvier. Model versions without Klt channels did
      not produce the sub-threshold effect. These results suggest that some such
      accumulation mechanism, along with Klt channels, may underlie sub-threshold
      masking observed in cat ANF responses. As multichannel auditory prostheses
      typically present sub-threshold stimuli to various ANF subsets, there is clear
      relevance of these findings to clinical situations.

PMID- 21080207
TI  - Molecular phylogenetic analyses of Tofieldiaceae (Alismatales): family
      circumscription and intergeneric relationships.
AB  - Tofieldiaceae are a small monocot family comprising about 20 species, mostly
      distributed in the Northern Hemisphere, with some in northern South America. To
      clarify the family circumscription, the number of distinguishable genera in the
      family, and relationships among the genera, we conducted molecular analyses of
      cpDNA (matK and non-coding trnL-trnL-trnF region) sequences of 17 associated
      species of Tofieldiaceae, along with 14 species of Acorales, Alismatales,
      Dioscoreales, Pandanales, and Liliales. Results showed that Tofieldiaceae are
      monophyletic, comprising all the species assignable to Harperocallis,
      Isidrogalvia, Pleea, Tofieldia, and Triantha, thus supporting the original family
      circumscription. Within the family, Pleea is sister to the rest of the family, in
      which Isidrogalvia is sister to Harperocallis, and Tofieldia to Triantha.
      Morphological characters supporting the relationships among the genera were
      briefly discussed.

PMID- 21080208
TI  - Evaluation of a multi-kinase inhibitor KRC-108 as an anti-tumor agent in vitro
      and in vivo.
AB  - Kinases have been studied as potential cancer targets because they play important
      roles in the cellular signaling of tumors. A number of small molecules targeting
      kinases are prescribed in clinics and many kinase inhibitors are being evaluated
      in the clinical phase. Previously, we discovered a series of aminopyridines
      substituted with benzoxazole as orally active c-Met kinase inhibitors. One of the
      compounds, KRC-108, has been evaluated as an anti-cancer agent in vitro and in
      vivo. A kinase panel assay exhibited that KRC-108 is a potent inhibitor of Ron,
      Flt3 and TrkA as well as c-Met. Moreover, KRC-108 inhibited oncogenic c-Met
      M1250T and Y1230D more strongly than wild type c-Met. The anti-proliferative
      activity of KRC-108 was measured by performing a cytotoxicity assay on a panel of
      cancer cell lines. The GI(50) values (i.e., 50% inhibition of cell growth) for
      KRC-108 ranged from 0.01 to 4.22 MUM for these cancer cell lines. KRC-108 was
      also effective for the inhibition of tumor growth in human HT29 colorectal cancer
      and NCI-H441 lung cancer xenograft models in athymic BALB/c nu/nu mice. This
      molecule should serve as a useful lead for inhibitors targeting kinases and may
      lead to new therapeutics for the treatment of cancer.

PMID- 21080209
TI  - Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin
      inhibits hepatic metastasis of colon cancer.
AB  - Liver metastasis is the major obstacle for prolonging the survival of colon
      cancer patients. Low-molecular-weight heparin (LMWH), a common drug for venous
      thromboembolism, has displayed beneficial effects in improving the survival of
      cancer patients, though the mechanism remains unclear. This study aimed to
      investigate the effects of LMWH on hepatic metastasis of colon cancer and its
      underlying molecular mechanism by targeting the interaction of the chemokine
      receptor CXCR4 and its ligand CXCL12 (formerly known as stromal cell-derived
      factor 1alpha, SDF-1alpha), as the CXCR4-CXCL12 axis has been shown to regulate
      the interaction of cancer cells and stroma. Experimental results revealed that
      LMWH (Enoxaparin, 3500-5500 Da) inhibited the CXCL12-stimulated proliferation,
      adhesion and colony formation of human colon cancer HCT-116 cells that highly
      expressed CXCR4. Interestingly, LMWH or an anti-CXCR4 blocking antibody
      diminished the migrating and invading abilities of HCT116 cells stimulated by the
      recombinant CXCL12 protein or liver homogenates which contained endogenous CXCL12
      protein. Although LMWH did not significantly inhibit the growth of subcutaneous
      colon tumors, it significantly suppressed the formation of hepatic metastasis
      established by intrasplenic injection of colon cancer cells in nude Balb/c mice
      and also downregulated the expression of CXCL12 in hepatic sinusoidal endothelial
      cells. The results suggest that LMWH inhibits the formation of hepatic metastasis
      of colon cancer by disrupting the interaction of CXCR4 and CXCL12, supporting
      that perioperative administration of LMWH may help to prevent the seeding and
      subsequent growth of hepatic metastases of colon cancer cells.

PMID- 21080210
TI  - A new diaryl urea compound, D181, induces cell cycle arrest in the G1 and M
      phases by targeting receptor tyrosine kinases and the microtubule skeleton.
AB  - Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including
      cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs
      have been validated as targets for cancer therapies. Microtubules are another
      class of proven targets for many clinical anticancer drugs. Here, we report that
      1-(4-chloro-3-(trifluoromethyl) phenyl)-3-(2-cyano-4-hydroxyphenyl)urea (D181)
      functions as both a receptor tyrosine kinase inhibitor and a tubulin
      polymerization enhancer. D181 displayed potent inhibitory activities against a
      panel of RTKs, including Flt3, VEGFR, cKit, FGFR1 and PDGFRbeta. D181 also
      enhanced tubulin polymerization and modified the secondary structure of tubulin
      proteins to disrupt their dynamic instability. Because of synergistic
      cooperation, D181 strongly inhibited the proliferation of various cancer cell
      lines, induced LoVo cell cycle arrest in the G1 and M phases and suppressed tumor
      growth in nude mice bearing human LoVo and HT29 xenografts. Our studies have
      provided a new, promising lead compound and novel clues for multi-target
      anticancer drug design and development.

PMID- 21080211
TI  - In vitro cytotoxicity of the novel antimyeloma agents perifosine, bortezomib and
      lenalidomide against different cell lines.
AB  - The novel AKT inhibitor perifosine, a synthetic alkylphospholipid, is currently
      being investigated in clinical trials for the treatment of different
      hematological and oncological malignancies. The in vitro cytotoxicity of
      perifosine, bortezomib and lenalidomide against 6 cell lines derived from
      hematological malignancies was investigated using trypan blue staining, flow
      cytometry-based detection of activated caspases, Annexin V assays,
      immunohistochemistry studies (KI-67 and caspase-3 staining) and the immature
      myeloid-information (IMI) technique. Perifosine and bortezomib induced
      concentration- and time-dependent cytotoxicity in all cell lines tested.
      Perifosine together with bortezomib largely exerted additive or synergistic
      effects with combination indices ranging from 1.13 to 0.22 for combined
      efficacies of 25% to 75% after 24-hour incubation. Lenalidomide-triggered
      cytotoxicity was low in all cell lines tested with any assay (less than 10%
      compared to the negative control). Finally, perifosine, but not bortezomib or
      lenalidomide, significantly increased the number of cells detected in the IMI
      channel. Perifosine and bortezomib- but not lenalidomide- trigger substantial
      cytotoxicity by caspase activation and mainly act additively or synergistically.
      The IMI technique might be a useful tool for studying cytotoxicity of agents like
      perifosine that interact mainly with the cellular membrane.

PMID- 21080212
TI  - Production of hyperthermostable GH10 xylanase Xyl10B from Thermotoga maritima in
      transplastomic plants enables complete hydrolysis of methylglucuronoxylan to
      fermentable sugars for biofuel production.
AB  - Overcoming the recalcitrance in lignocellulosic biomass for efficient hydrolysis
      of the polysaccharides cellulose and hemicellulose to fermentable sugars is a
      research priority for the transition from a fossilfuel-based economy to a
      renewable carbohydrate economy. Methylglucuronoxylans (MeGXn) are the major
      components of hemicellulose in woody biofuel crops. Here, we describe efficient
      production of the GH10 xylanase Xyl10B from Thermotoga maritima in transplastomic
      plants and demonstrate exceptional stability and catalytic activities of the in
      planta produced enzyme. Fully expanded leaves from homotransplastomic plants
      contained enzymatically active Xyl10B at a level of 11-15% of their total soluble
      protein. Transplastomic plants and their seed progeny were morphologically
      indistinguishable from non-transgenic plants. Catalytic activity of in planta
      produced Xyl10B was detected with poplar, sweetgum and birchwood xylan substrates
      following incubation between 40 and 90  degrees C and was also stable in dry and
      stored leaves. Optimal yields of Xyl10B were obtained from dry leaves if crude
      protein extraction was performed at 85  degrees C. The transplastomic plant
      derived Xyl10B showed exceptional catalytic activity and enabled the complete
      hydrolysis of MeGXn to fermentable sugars with the help of a single accessory
      enzyme (alpha-glucuronidase) as revealed by the sugar release assay. Even without
      this accessory enzyme, the majority of MeGXn was hydrolyzed by the transplastomic
      plant-derived Xyl10B to fermentable xylose and xylobiose.

PMID- 21080213
TI  - Return-to-work activities in a Chinese cultural context.
AB  - INTRODUCTION: Several studies have been conducted in the West showing that return
      to work (RTW) coordination is a key element to facilitate RTW of injured workers
      and to prevent work disabilities. However, no study has been carried out to
      investigate the scope of RTW activities in China. The purpose of this study was
      to explore the views of key RTW stakeholders on necessary activities for RTW
      coordination. METHODS: A cross-sectional survey was conducted in Guangdong
      province of China. A three-tiered approach including focus group discussions and
      panel reviews was used to collect RTW activities, analyze the content validity,
      and classify domains. Descriptive statistics and intra-class correlation (ICC)
      were used to describe the importance of RTW activities and the degree of
      agreement on the classification of different domains. A Kruskal-Wallis test with
      subsequent post-hoc analysis using multiple Mann-Whitney U tests was carried out
      to check for any differences in the domains of different RTW activities among RTW
      stakeholders. RESULTS: The domains of RTW activities in China were similar to
      those in the West and included workplace assessment and mediation, social problem
      solving, role and liability clarification, and medical advice. Good agreement
      (ICC: 0.729-0.844) on the classification of RTW activities into different domains
      was found. The domains of the RTW activities of healthcare providers differed
      from those of employers (P = 0.002) and injured workers (P = 0.001). However,
      there was no significant difference between employers and injured workers.
      CONCLUSIONS: This study indicated that differences among stakeholders were
      observed in terms of areas of relative priority. There is a clear need for
      research and training in China to establish a nation-wide terminology for RTW
      coordination, facilitate cross-provincial studies and work toward a more
      integrated system addressing the diverse perspectives of stakeholders involved in
      the RTW process.

PMID- 21080215
TI  - Effects of NYGGF4 knockdown on insulin sensitivity and mitochondrial function in
      3T3-L1 adipocytes.
AB  - NYGGF4 is a recently discovered gene that is involved in obesity-associated
      insulin resistance. It has been suggested that mitochondrial dysfunction might be
      responsible for the development of insulin resistance induced by NYGGF4
      overexpression. In the present study, we aimed to define the impact of down
      regulating NYGGF4 expression by RNA interference (RNAi) on the insulin
      sensitivity and mitochondrial function of 3T3-L1 adipocytes. The results revealed
      that NYGGF4 knockdown enhanced the glucose uptake of adipocytes, which
      reconfirmed the regulatory function of NYGGF4 in adipocyte insulin sensitivity.
      However, an unexpected observation was that knockdown of NYGGF4 reduced
      intracellular ATP concentration and promoted an increase in mitochondrial
      transmembrane potential (DeltaPsim) and reactive oxygen species (ROS) level
      without affecting mitochondrial morphology or mtDNA. Therefore, the role of
      NYGGF4 in mitochondrial function remains unclear, and further animal studies are
      needed to explore the biological function of this gene.

PMID- 21080214
TI  - Work and health, a blind spot in curative healthcare? A pilot study.
AB  - INTRODUCTION: Most workers with musculoskeletal disorders on sick leave often
      consult with regular health care before entering a specific work rehabilitation
      program. However, it remains unclear to what extent regular healthcare
      contributes to the timely return to work (RTW). Moreover, several studies have
      indicated that it might postpone RTW. There is a need to establish the influence
      of regular healthcare on RTW as outcome; "Does visiting a regular healthcare
      provider influence the duration of sickness absence and recurrent sick leave due
      to musculoskeletal disorders?". METHODS: A cohort of workers on sick leave for 2
      6 weeks due to a-specific musculoskeletal disorders was followed for 12 months.
      The main outcomes for the present analysis were: duration of sickness absence
      till 100% return to work and recurrent sick leave after initial RTW. Cox
      regression analyses were conducted with visiting a general health practitioner,
      physical therapist, or medical specialist during the sick leave period as
      independent variables. Each regression model was adjusted for variables known to
      influence health care utilization like age, sex, diagnostic group, pain
      intensity, functional disability, general health perception, severity of
      complaints, job control, and physical load at work. RESULTS: Patients visiting a
      medical specialist reported higher pain intensity and more functional limitations
      and also had a worse health perception at start of the sick leave period compared
      with those not visiting a specialist. Visiting a medical specialist delayed
      return to work significantly (HR = 2.10; 95%CI 1.43-3.07). After approximately 8
      weeks on sick leave workers visiting a physical therapist returned to work faster
      than other workers. A recurrent episode of sick leave during the follow up quick
      was initiated by higher pain intensity and more functional limitations at the
      moment of fully return to work. Visiting a primary healthcare provider during the
      sickness absence period did not influence the occurrence of a new sick leave
      period. CONCLUSION: Despite the adjustment for severity of the musculoskeletal
      disorder, visiting a medical specialist was associated with a delayed full return
      to work. More attention to the factor 'labor' in the regular healthcare is
      warranted, especially for those patients experiencing substantial functional
      limitations due to musculoskeletal disorders.

PMID- 21080216
TI  - Brief report: broader autism phenotype predicts spontaneous reciprocity of direct
      gaze.
AB  - We report evidence for a relationship in the general population between self
      reported autism-associated traits and the spontaneous reciprocation of direct
      gaze, a behavior that we propose may reflect a tendency to synchronize with
      social partners. Adults viewed videos of actors whose gaze was either directed
      towards or averted from them. Individuals with lower scores on four subscales of
      the Autism-Spectrum Quotient (AQ) scale showed a greater tendency to look at
      directed relative to averted eyes; individuals with higher scores on the AQ did
      not. This relationship was specific to autism-associated traits and to gaze
      towards the eyes; it did not generalize to a social anxiety measure or to gaze
      towards the mouth. We discuss implications for our understanding of the broader
      autism phenotype.

PMID- 21080218
TI  - Effects of workshop training for providers under mandated use of an evidence
      based practice.
AB  - Workshops are a common strategy for fostering the adoption of evidence-based
      practices (EBP), but workshops alone may not change provider behavior. This study
      investigates the impact of a two-day training combined with an existing mandate
      for EBP use. Providers attending regional workshops showed improved attitudes
      toward the behavioral parent training model, but not EBPs in general.
      Participants were more accepting of behavioral techniques shortly after training,
      but the effect was not maintained. Examination of youth served prior to and after
      the training showed that providers increased their use of the EBP but overall
      outcomes were not improved.

PMID- 21080217
TI  - Delineation of behavioral phenotypes in genetic syndromes: characteristics of
      autism spectrum disorder, affect and hyperactivity.
AB  - We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and
      affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS;
      58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS;
      189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD
      symptomatology was heightened in CdLS and FXS. High levels of impulsivity were
      seen in SMS, AS, CdCS, FXS and adults with CdLS. Negative affect was prominent in
      adults with CdLS, while positive affect was prominent in adults with AS and FXS.
      Heightened levels of overactivity and impulsivity were identified in FXS, AS and
      SMS while low levels were identified in PWS. These findings confirm and extend
      previously reported behavioral phenotypes.

PMID- 21080219
TI  - A geographic analysis of chronically homeless adults before and after enrollment
      in a multi-site supported housing initiative: community characteristics and
      migration.
AB  - The current study examined the community characteristics and migration of
      chronically homeless adults before and after entry into a multi-site supported
      housing initiative. A total of 394 participants were geocoded at baseline and 12
      month follow up. Data from geographic information systems indicate that the
      median distance participants traveled from their last residence to their
      residence 1 year after program entry was 4.6 miles and 12% of participants
      traveled more than 100 miles. Participants moved into communities with higher
      population densities, larger proportions of Whites, and smaller proportions of
      Blacks following their entry into supported housing, but continued to live in
      communities with higher crime rates, lower education levels, and lower income
      levels then the state average. At 12 months, Black participants residing in
      communities with higher population densities and larger Black populations
      reported higher social support and lower subjective distress. This underscores
      the importance of considering client preferences in housing. Together, these
      findings suggest that supported housing programs may be successful in finding
      housing for homeless clients, but are not placing them in improved communities.
      Special attention may also be needed for some clients who travel long distances
      between residences.

PMID- 21080220
TI  - Differential toxicological effects induced by mercury in gills from three
      pedigrees of Manila clam Ruditapes philippinarum by NMR-based metabolomics.
AB  - Mercury is a hazardous pollutant in the Bohai marine environments due to its high
      toxicity to the marine organisms and subsequent ecological risk. Manila clam
      Ruditapes philippinarum is one of important sentinel organisms in 'Mussel Watch
      Program' launched in China and therefore used as a bioindicator in marine and
      coastal ecotoxicology. There are dominantly distributed three pedigrees of clam
      (White, Liangdao Red and Zebra) in Yantai population endowed with different
      tolerances to environmental stressors. In this study, gill tissues were collected
      from both untreated and mercury exposed White, Liangdao Red and Zebra clams, and
      the extracts were analyzed by NMR-based metabolomics to compare the original
      metabolomes and the toxicological effects induced by mercury exposure in three
      pedigrees. The major abundant metabolites in White clam sample were branched
      chain amino acids, lactate, alanine, arginine, acetoacetate, glutamate,
      succinate, citrate, malonate and taurine, while the metabolite profile of
      Liangdao Red clam sample comprises relative high levels of alanine, arginine,
      glutamate, succinate and glycogen. For Zebra clam sample, the metabolite profile
      exhibited relatively high amount of aspartate, acetylcholine and homarine. After
      48 h exposure of 20 MUg l(-1) Hg(2+), the metabolic profiles from all the three
      pedigrees of clams commonly showed significant increases in alanine, arginine,
      glutamate, aspartate, alpha-ketoglutarate, glycine and ATP/ADP, and decreases in
      citrate, taurine and homarine. The unique metabolic differences between the
      metabolomes of gill tissues from Hg(2+)-exposed White, Liangdao Red and Zebra
      clams were found, including elevated acetylcholine and branched-chain amino acids
      in White clams, and the declined succinate in both White and Liangdao Red samples
      as well as the declined betaine in Zebra and White clams. Overall, our findings
      showed the differential toxicological responses to mercury exposure and that
      White clams could be a preferable bioindicator for the metal pollution monitoring
      based on the metabolic changes from gill compared with other two (Liangdao Red
      and Zebra) pedigrees of clams.

PMID- 21080221
TI  - Phytoremediation of metals from fly ash through bacterial augmentation.
AB  - Different combinations of four bacterial strains isolated from fly ash were used
      by us to study their impact on phytoextraction of metals from fly ash by Brassica
      juncea grown in fly ash amended with farm yard manure (50:50 w/w). Out of 11
      bacterial consortia, a combination of two strains i.e. Paenibacillus macerans
      NBRFT5 + Bacillus pumilus NBRFT9 (C7) inoculated in the rhizosphere was found to
      enhance Pb accumulation maximally by 278%, Mn by 75%, Zn by 163%, Cr by 226% and
      Ni by 414% compared to control. It is possible that these bacteria, known for
      N(2) fixation, solubilization of phosphorus and uptake of micronutrient, could
      promote the plant growth resulting in higher accumulation of metals. However, a
      combination of four bacteria, namely Micrococcus roseus NBRFT2 + Bacillus
      endophyticus NBRFT4 + Paenibacillus macerans NBRFT5 + Bacillus pumilus NBRFT9
      (C4) was able to increase Cd uptake maximally by 237%. Further, the translocation
      of metal was invariably more from root to stem than from stem to leaf which was
      regulated by plant transport mechanism and metal mobility. Bacteria are known to
      excrete protons, organic acids, enzymes and siderophores to enhance the
      mobilization of metals which boosted the phytoextraction of metals from fly ash.

PMID- 21080222
TI  - A meta-analysis of experiments testing the effects of a neonicotinoid insecticide
      (imidacloprid) on honey bees.
AB  - Honey bees provide important pollination services to crops and wild plants. The
      agricultural use of systemic insecticides, such as neonicotinoids, may harm bees
      through their presence in pollen and nectar, which bees consume. Many studies
      have tested the effects on honey bees of imidacloprid, a neonicotinoid, but a
      clear picture of the risk it poses to bees has not previously emerged, because
      investigations are methodologically varied and inconsistent in outcome. In a meta
      analysis of fourteen published studies of the effects of imidacloprid on honey
      bees under laboratory and semi-field conditions that comprised measurements on
      7073 adult individuals and 36 colonies, fitted dose-response relationships
      estimate that trace dietary imidacloprid at field-realistic levels in nectar will
      have no lethal effects, but will reduce expected performance in honey bees by
      between 6 and 20%. Statistical power analysis showed that published field trials
      that have reported no effects on honey bees from neonicotinoids were incapable of
      detecting these predicted sublethal effects with conventionally accepted levels
      of certainty. These findings raise renewed concern about the impact on honey bees
      of dietary imidacloprid, but because questions remain over the environmental
      relevance of predominantly laboratory-based results, I identify targets for
      research and provide procedural recommendations for future studies.

PMID- 21080223
TI  - Performance of standard media in toxicological assessments with Daphnia magna:
      chelators and ionic composition versus metal toxicity.
AB  - Fully artificial test media can increase reproducibility and standardization in
      ecotoxicological assessments, but there is still a lack of convergence among
      ecotoxicology laboratories in aquatic test media with respect to ionic
      composition, chelators, and organic supplements. We compared the performance of
      Daphnia magna in three widely-used reconstituted media. The tested media differed
      in composition: (a) ADaM, an artificial medium based in a synthetic sea salt,
      with no a priori known chelating properties; (b) ASTM hard water supplemented
      with algal extract, a semi-artificial medium with unknown chelating properties;
      and (c) M7, a complex artificial medium containing EDTA as a chelator. All three
      media were suitable for rearing D. magna (although performance in M7 was
      suboptimal) and acute EC(50) values for reference substances (3,4-DCA,
      K(2)Cr(2)O(7)) were similar between media. In acute exposures to Cu and Cd,
      daphniids were least sensitive when reared in M7, as expected due to metal
      chelation by EDTA. Daphnia sensitivity to Cd was low in ADaM. Thus, these two
      media were suboptimal for assessing the toxicity of some metals to D. magna in
      acute tests. We suggest that both the ionic composition of the medium and the
      presence of chelators should be taken into account when metal toxicity is
      concerned. Chronic toxicity profiles for Cu suggested a mild chelating effect of
      the algal extract in ASTM medium. Still, ASTM hard water persists as one of the
      most suitable media for acute toxicity assessments of metals and metal
      contaminated samples.

PMID- 21080224
TI  - Catalase in fluvial biofilms: a comparison between different extraction methods
      and example of application in a metal-polluted river.
AB  - Antioxidant enzymes are involved in important processes of cell detoxification
      during oxidative stress and have, therefore, been used as biomarkers in algae.
      Nevertheless, their limited use in fluvial biofilms may be due to the complexity
      of such communities. Here, a comparison between different extraction methods was
      performed to obtain a reliable method for catalase extraction from fluvial
      biofilms. Homogenization followed by glass bead disruption appeared to be the
      best compromise for catalase extraction. This method was then applied to a field
      study in a metal-polluted stream (Riou Mort, France). The most polluted sites
      were characterized by a catalase activity 4-6 times lower than in the low
      polluted site. Results of the comparison process and its application are
      promising for the use of catalase activity as an early warning biomarker of
      toxicity using biofilms in the laboratory and in the field.

PMID- 21080226
TI  - Breeding strategy and organochlorine contamination of eggs in lesser scaup
      (Aythya affinis).
AB  - We explored relationships between breeding strategy and contaminant importation
      and depuration into lesser scaup (Aythya affinis) eggs. Our primary hypothesis
      was that females accumulate organochlorine (OC) contaminants in lipid reserves
      obtained on wintering and spring staging areas and depurate those contaminants
      into eggs on the breeding area proportional to the amount of endogenous reserves
      used for egg formation. Egg collection occurred at Red Rock Lakes National
      Wildlife Refuge, Montana, in 2006 for contaminant and stable isotope analysis.
      Eggs were assayed for 22 lipophilic OCs and endogenous lipid reserves for each
      egg were estimated using carbon (delta(13)C) stable isotope values. Of the 22 OC
      analytes tested for, only p,p'-DDE was detected in all samples, oxychlordane was
      detected in 56%, and no other OC analytes tested for were detected in >50% of
      samples. The mean percent contribution of endogenous reserves to egg lipids in
      scaup was 37.9 +/- 0.05%, ranging from 0-88.2%. We found little support for the
      hypothesized relationship between breeding strategy and egg contaminant levels.
      No significant trend was observed for endogenous reserves and egg contaminant
      levels of p,p'-DDE or oxychlordane (R (2) < 0.01, P = 0.792; R (2) < 0.01, P =
      0.674, respectively). Thus, our results did not indicate that breeding females
      are importing contaminants from wintering or spring staging areas and depurating
      those contaminants into their clutches.

PMID- 21080225
TI  - Biochemical characterization of cholinesterases in Enchytraeus albidus and
      assessment of in vivo and in vitro effects of different soil properties, copper
      and phenmedipham.
AB  - Enchytraeus albidus are important organisms of the soil biocenosis, used as
      standard test species in environmental risk assessment. The inhibition of
      cholinesterases (ChE) activity of several species has been widely used to assess
      the exposure and effects of anti-cholinesterase environmental contaminants.
      Several studies have shown the association between ChE activity inhibition and
      adverse effects on behaviour and survival. Extensive studies addressing survival
      and behavioural endpoints, as well as other biomarkers, have been done in E.
      albidus with different types of soil contaminants. The main objectives of this
      study were: (1) to characterize biochemically the ChE present in the soluble post
      mitochondrial fraction of E. albidus whole body homogenates, using different
      substrates and selective inhibitors; (2) to assess the in vivo effects of copper,
      phenmedipham and different soil properties (pH, organic matter, clay) on the ChE
      activity; (3) to assess the in vitro effects of copper and phenmedipham on the
      ChE activity. The results suggest the presence of one ChE in the soluble post
      mitochondrial fraction of E. albidus whole body homogenates, which displays
      properties of both acetylcholinesterase and pseudocholinesterase considering the
      typical mammalian enzymes. It is also shown that ChE activity is not inhibited by
      exposure to different soil properties and that copper and phenmedipham inhibited
      ChE activity both in in vivo and in in vitro conditions and therefore ChE
      inhibition seems to be a robust biomarker for this herbicide and this heavy
      metal. This study showed that ChE activity in E. albidus might be correlated to
      previously determined higher level effects like survival and reproduction, as
      well as avoidance behaviour.

PMID- 21080227
TI  - Prevalence and economic implications of calf foetal wastage in an abattoir in
      Northcentral Nigeria.
AB  - The study was conducted to evaluate the volume of pregnant cows slaughtered at
      Minna abattoir, Niger State, Nigeria between 2001 and 2009 based on abattoir meat
      inspection records. Of the 98,407 cows slaughtered, 4,368 were pregnant,
      translating to a ratio of one calf foetal wastage in every 23 cows slaughtered.
      The wastage was significantly (P<0.05) high during the early rainy season (April
      to June). There was no significant difference observed across the years. The
      economic impact of the wastage is estimated at N8, 353,800.00 ($56,828.57) which
      is a great loss to the livestock industry. With these findings, there is the need
      to advocate for adequate enforcement of legislations on routine veterinary
      examinations at the slaughter houses in Nigeria. Also, livestock owners should be
      educated on the seasonal breeding patterns of cattle in order to avoid selling
      cows during the calving season to salvage high level of calf foetal wastage.

PMID- 21080228
TI  - Comparative multivariate analysis of biometric traits of West African Dwarf and
      Red Sokoto goats.
AB  - The population structure of 302 randomly selected West African Dwarf (WAD) and
      Red Sokoto (RS) goats was examined using multivariate morphometric analyses. This
      was to make the case for conservation, rational management and genetic
      improvement of these two most important Nigerian goat breeds. Fifteen
      morphometric measurements were made on each individual animal. RS goats were
      superior (P<0.05) to the WAD for the body size and skeletal proportions
      investigated. The phenotypic variability between the two breeds was revealed by
      their mutual responses in the principal components. While four principal
      components were extracted for WAD goats, three components were obtained for their
      RS counterparts with variation in the loading traits of each component for each
      breed. The Mahalanobis distance of 72.28 indicated a high degree of spatial
      racial separation in morphology between the genotypes. The Ward's option of the
      cluster analysis consolidated the morphometric distinctness of the two breeds.
      Application of selective breeding to genetic improvement would benefit from the
      detected phenotypic differentiation. Other implications for management and
      conservation of the goats are highlighted.

PMID- 21080229
TI  - Haematopoietic stem cell transplantation does not retard disease progression in
      the psycho-cognitive variant of late-onset metachromatic leukodystrophy.
AB  - Haematopoietic stem cell transplantation has an unproven role in the management
      of late-onset metachromatic leukodystrophy: theoretically justified through the
      engraftment of enzyme-replete haematopoietic progenitors and restoration of
      capacity for sulphatide catabolism in neural tissue through enzyme recapture, the
      long-term outcome is unknown. The rarity of the psycho-cognitive variant and slow
      progression of late-onset disease impairs evaluation of treatment. We report
      detailed clinical and neuropsychological assessments after haematopoietic stem
      cell transplantation in a patient with a late-onset psycho-cognitive form of
      metachromatic leukodystrophy. Cognitive decline, indistinguishable from the
      natural course of the disease, was serially documented over 11 years despite
      complete donor chimaerism and correction of leukocyte arylsulphatase A to wild
      type values; subtle motor deterioration was similarly noted and progressive
      cerebral volume loss was evident upon magnetic resonance imaging. Sensory nerve
      conduction deteriorated 17 months post-transplantation with apparent
      stabilisation at 11-year review. Haematopoietic stem-cell transplantation was
      ineffective for this rare attenuated variant of metachromatic leukodystrophy. In
      the few patients identified pre-symptomatically or with early-phase disease,
      clear recommendations are lacking; when transplantation is considered, umbilical
      cord blood grafts from enzyme-replete donors with adjunctive mesenchymal stem
      cell infusions from the same source may be preferable. Improved outcomes will
      depend on enhanced awareness and early diagnosis of the disease, so that
      promising interventions such as genetically modified, autologous stem cell
      transplantation have the best opportunity of success.

PMID- 21080230
TI  - Respect for cultural diversity in bioethics. Empirical, conceptual and normative
      constraints.
AB  - In contemporary debates about the nature of bioethics there is a widespread view
      that bioethical decision making should involve certain knowledge of and respect
      for cultural diversity of persons to be affected. The aim of this article is to
      show that this view is untenable and misleading. It is argued that introducing
      the idea of respect for cultural diversity into bioethics encounters a series of
      conceptual and empirical constraints. While acknowledging that cultural diversity
      is something that decision makers in bioethical contexts should try to understand
      and, when possible, respect, it is argued that this cultural turn ignores the
      typically normative role of bioethics and thus threatens to undermine its very
      foundations.

PMID- 21080231
TI  - Impact of indium-111 oxine labelling on viability of human mesenchymal stem cells
      in vitro, and 3D cell-tracking using SPECT/CT in vivo.
AB  - PURPOSE: This study investigates the effects of (111)In-oxine incorporation on
      human mesenchymal stem cells' (hMSC) biology and viability, and the applicability
      of (111)In-oxine for single-photon emission computed tomography/X-ray computed
      tomography (SPECT/CT) monitoring of hMSC in vivo. PROCEDURES: HMSC were labelled
      with 10 Bq/cell. Cellular retention of radioactivity, cell survival, and
      migration were evaluated over 48 h. Metabolic activity was assessed over 14 days
      and the hMSC's stem cell character was evaluated. Serial SPECT/CT was performed
      after intra-osseous injection to athymic rats over 48 h. RESULTS: Labelling
      efficiency was 25%, with 61% of incorporated (111)In remaining in the hMSC at 48
      h. The radiolabelling was without effect on cell viability, stem cell character,
      and plasticity, whereas metabolic activity and migration were significantly
      reduced. Grafted cells could be imaged in situ with SPECT/CT. CONCLUSIONS:
      (111)In-oxine labelling moderately impaired hMSC's functional integrity while
      preserving their stem cell character. Combined SPECT/CT imaging of (111)In-oxine
      labelled hMSC opens the possibility for non-invasive sequential monitoring of
      therapeutic stem cells.

PMID- 21080232
TI  - Impact of dedicated brain PET on intended patient management in participants of
      the national oncologic PET Registry.
AB  - PURPOSE: This study seeks to assess the impact of dedicated brain positron
      emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose on intended
      management of patients with primary and metastatic brain tumors. PROCEDURES: We
      analyzed demographic characteristics and evaluated change in intended management
      after PET, using previously described metrics, for patients in the National
      Oncologic PET Registry (NOPR) undergoing dedicated brain PET. For cases of
      primary brain tumors, comparisons to the overall NOPR cohort were made. PATIENT
      PROFILE: Between December 2006 and April 2009, 509 dedicated brain PET scans were
      done on 479 patients--367 (72.1%) for suspected or proven primary brain tumors
      and 142 (27.9%) for brain metastases. Compared with the overall NOPR cohort,
      subjects in the dedicated brain cohort were younger (41.3% less than 65 years vs.
      10.5% overall, p < 0.0001) and more frequently had functional limitations from
      their cancers (78.6% vs. 62.3% overall; odds ratio (OR) 2.2, 95% CI 1.8-2.8).
      RESULTS: The pre-PET patient management plans in the primary brain tumor and
      metastasis subgroups were similar. A pre-PET plan of tissue biopsy was slightly
      more frequent than one of the treatments (31.3% vs. 28.6%) in the primary brain
      tumor subgroup and was more common than in the overall NOPR cohort (14.2%; OR
      2.8, 95% CI 2.2-3.5). Changes from treatment to non-treatment also were more
      frequent than in the overall NOPR cohort (13.4% vs. 7.7%; OR 1.9, 95% CI 1.3
      2.5). CONCLUSIONS: Among NOPR patients, dedicated brain PET was associated with
      similar net changes in intended management as in the overall NOPR cohort.
      However, brain PET patients were younger, more likely to be symptomatic, and less
      likely to have a change in management from non-treatment to treatment as a post
      PET plan.

PMID- 21080233
TI  - Trafficking of a dual-modality magnetic resonance and fluorescence imaging
      superparamagnetic iron oxide-based nanoprobe to lymph nodes.
AB  - PURPOSE: This study aims to develop and characterize the trafficking of a dual
      modal agent that identifies primary draining or sentinel lymph node (LN).
      PROCEDURE: Herein, a dual-reporting silica-coated iron oxide nanoparticle (SCION)
      is developed. Nude mice were imaged by magnetic resonance (MR) and optical
      imaging and axillary LNs were harvested for histological analysis. Trafficking
      through lymphatics was observed with intravital and ex vivo confocal microscopy
      of popliteal LNs in B6-albino, CD11c-EYFP, and lys-EGFP transgenic mice. RESULTS:
      In vivo, SCION allows visualization of LNs. The particle's size and surface
      functionality play a role in its passive migration from the intradermal injection
      site and its minimal uptake by CD11c+ dendritic cells and CD169+ and lys+
      macrophages. CONCLUSIONS: After injection, SCION passively migrates to LNs
      without macrophage uptake and then can be used to image LN(s) by MRI and
      fluorescence. Thus, SCION can potentially be developed for use in sentinel node
      resections or for intralymphatic drug delivery.

PMID- 21080234
TI  - Presence of apolipoprotein C-III attenuates apolipoprotein E-mediated cellular
      uptake of cholesterol-containing lipid particles by HepG2 cells.
AB  - Apolipoprotein C-III (apoC-III) decreases the apolipoprotein E (apoE)-mediated
      uptake of lipoprotein remnants by the liver, and a high plasma concentration of
      apoC-III in VLDL is associated with hypertriglyceridemia and the risk of coronary
      heart disease. In this study, we prepared lipid emulsions containing triolein,
      phosphatidylcholine and cholesterol as model particles of lipoproteins, and
      examined the roles of apoC-III in apoE-mediated uptake of emulsions by HepG2
      cells. Cholesterol in emulsion particles enhanced the apoE-mediated uptake via
      heparan sulfate proteoglycan and LDL receptor-related protein pathways. The
      amount of apoE bound to emulsion particles was increased by the presence of
      cholesterol at the particle surface, whereas cholesterol had no effect on the
      binding amount of apoC-III. Surface cholesterol alleviated the inhibitory effect
      of apoC-III on apoE incorporation into the emulsion surface. However, ApoC-III
      almost completely inhibited the apoE-mediated uptake of cholesterol-containing
      emulsions despite sufficient binding of apoE to emulsions. These findings suggest
      that apoC-III attenuates the binding of apoE to the lipoprotein surface and apoE
      mediated cellular uptake of lipoprotein remnants. Furthermore, cholesterol may
      affect these functions of apoC-III and apoE involved in the clearance of
      lipoprotein remnants.

PMID- 21080235
TI  - Two new eicosanoids with a unique isovalerianic acid ester moiety from the South
      China Sea gorgonian Dichotella gemmacea.
AB  - Two new eicosanoids with a unique isovalerianic acid ester group at C-12, named
      dichotellates A (1) and B (2), were isolated from the gorgonian Dichotella
      gemmacea collected from the South China Sea using bioassay-guided fractionation.
      Their structures were established on the basis of extensive spectroscopic
      analysis including one-dimensional (1D) and two-dimensional (2D) NMR as well as
      high-resolution ESI-MS experiments. These two compounds were evaluated for their
      lethal activity toward brine shrimp Artemia salina and both showed weak activity.

PMID- 21080236
TI  - Abstracts of the Irish Society for Rheumatology & Irish Rheumatology Health
      Professionals Society - Autumn Scientific Meeting. Belfast, Northern Ireland.
      September 24-25, 2009.

PMID- 21080239
TI  - Ethnicity and second-line antihypertensive medication response in the ASCOT
      Trial.

PMID- 21080238
TI  - The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA
      receptors.
AB  - The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand
      gated ion channels that play crucial roles in synaptic transmission and
      plasticity. Our knowledge about the ultrastructure and subunit assembly
      mechanisms of intact AMPA-Rs was very limited. However, the new studies using
      single particle EM and X-ray crystallography are revealing important insights.
      For example, the tetrameric crystal structure of the GluA2cryst construct
      provided the atomic view of the intact receptor. In addition, the single particle
      EM structures of the subunit assembly intermediates revealed the conformational
      requirement for the dimer-to-tetramer transition during the maturation of AMPA
      Rs. These new data in the field provide new models and interpretations. In the
      brain, the native AMPA-R complexes contain auxiliary subunits that influence
      subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the
      mechanisms of the auxiliary subunits will become increasingly important to
      precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics
      studies continuously reveal a previously unexpected degree of molecular
      heterogeneity of the complex. Because the AMPA-Rs are important drug targets for
      treating various neurological and psychiatric diseases, it is likely that these
      new native complexes will require detailed mechanistic analysis in the future.
      The current ultrastructural data on the receptors and the receptor-expressing
      stable cell lines that were developed during the course of these studies are
      useful resources for high throughput drug screening and further drug designing.
      Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R
      mediated synaptic plasticity.

PMID- 21080242
TI  - Future therapies for the myeloproliferative neoplasms.
AB  - Ever since their description as "myeloproliferative syndromes" by William
      Dameshek in 1951, the myeloproliferative neoplasms (MPNs) have been managed by
      the selective use of rather mundane, nonspecific therapies that rely on either
      antiplatelet effects or myelosuppression. The year 2005 ushered in a new era of
      drug development and discovery for the MPNs after the description of the JAK2
      V617F mutation and the role this constitutively active tyrosine kinase has in MPN
      pathogenesis. Subsequently, multiple pharmacologic agents have begun (or are
      about to begin) testing for the inhibition of JAK2 in an attempt to improve the
      treatment of MPNs. Both primary myelofibrosis and myelofibrosis following
      essential thrombocythemia or polycythemia vera have been the targets of the most
      extensive testing of these agents to date. Responses to these oral JAK2
      inhibitors have been primarily intended to reduce splenomegaly and meaningfully
      improve symptoms; effects on the JAK2 V617F allele burden or marrow histology are
      limited. Toxicities have ranged from myelosuppression to significant diarrhea.
      Additional agents with other mechanisms of action are also targeting JAK2,
      including histone deacetylase inhibitors and mTOR inhibitors. The results of
      preliminary trials of JAK2 inhibitors in polycythemia vera and essential
      thrombocythemia have been mixed but are premature. Many questions remain as to
      the optimal JAK2 inhibitory strategy and the full extent of the benefit of single
      agent JAK2 inhibition.

PMID- 21080240
TI  - Research advances in amyotrophic lateral sclerosis, 2009 to 2010.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of upper and
      lower motor neurons that causes progressive weakness and death. The breadth of
      research in ALS continues to grow with exciting new discoveries in disease
      pathogenesis and potential future therapeutics. There is a growing list of
      identified mutations in familial ALS, including those in genes encoding TDP-43
      and FUS/TLS, which are expanding our understanding of the role of RNA modulation
      in ALS pathogenesis. There is a greater appreciation for the role of glial cells
      in motor neuron disease. Mitochondrial dysfunction is also being shown to be
      critical for motor neuron degeneration. In addition to pharmacotherapy, there are
      promising early developments with therapeutic implications in the areas of RNA
      interference, stem cell therapies, viral vector-mediated gene therapy, and
      immunotherapy. With greater understanding of ALS pathogenesis and exciting new
      therapeutic technologies, there is hope for future progress in treating this
      disease.

PMID- 21080241
TI  - Update on Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth disease (CMT) disease encompasses a genetically heterogeneous
      group of inherited neuropathies, also known as hereditary motor and sensory
      neuropathies. CMT results from mutations in more than 40 genes expressed in
      Schwann cells and neurons causing overlapping phenotypes. The classic CMT
      phenotype reflects length-dependent axonal degeneration characterized by distal
      sensory loss and weakness, deep tendon reflex abnormalities, and skeletal
      deformities. Recent articles have provided insight into the molecular
      pathogenesis of CMT, which, for the first time, suggest potential therapeutic
      targets. Although there are currently no effective medications for CMT, multiple
      clinical trials are ongoing or being planned. This review will focus on the
      underlying pathomechanisms and diagnostic approaches of CMT and discuss the
      emerging therapeutic strategies.

PMID- 21080243
TI  - The emerging role of histone deacetylase inhibitors in treating T-cell lymphomas.
AB  - T-cell lymphomas are an uncommon and heterogeneous group of non-Hodgkin
      lymphomas. Historically, therapies for these diseases have been borrowed from
      treatments for other lymphomas. More recently, efforts have be made to identify
      novel agents for their activity specifically in T-cell lymphomas. A primary
      example of new agents with specific activity in T-cell lymphomas is the novel
      class of drug, histone deacetylase inhibitors. The potential activity of histone
      deacetylase inhibitors was discovered somewhat serendipitously, but these early
      discoveries were followed by some larger and more rigorous studies in T-cell
      lymphomas. Two compounds, vorinostat and romidepsin, are currently approved and
      are in clinical use for the treatment of cutaneous T-cell lymphomas. Other drugs
      are in development, and a large study of romidepsin in peripheral T-cell lymphoma
      has recently been completed. This review covers data on the use of histone
      deacetylase inhibitors in T-cell lymphomas, as well as early attempts, just
      beginning, to combine these agents with other novel therapies.

PMID- 21080244
TI  - The IL-28 genotype: how it will affect the care of patients with hepatitis C
      virus infection.
AB  - The hypothesis that host genetics play an essential role in the ability not only
      to clear acute hepatitis C infection but also to achieve sustained virologic
      response (SVR) to interferon (IFN)-based therapy has been proved with the recent
      discovery of two single-nucleotide polymorphisms on chromosome 19. Variants in
      the minor allele rs8099917 and the proximate polymorphism rs12979860, 3 kb
      upstream of the interleukin (IL)-28B gene, which encodes the endogenous antiviral
      cytokine IFN-lambda, are associated with SVR and with natural viral clearance.
      The disparate frequencies of these alleles in ethnic groups worldwide may well
      explain differing rates of SVR among them. The test for one of these
      polymorphisms is now commercially available and can serve as a powerful predictor
      of a patient's chance of achieving SVR. Perhaps more importantly, the test can
      help the clinician personally tailor the duration and even the type of therapy
      that is most appropriate for an individual patient, newly or chronically infected
      with the hepatitis C virus.

PMID- 21080245
TI  - A clinical perspective on gastric neuroendocrine neoplasia.
AB  - The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially
      based on widespread use of endoscopy and a greater pathological awareness of the
      condition. A key concern is the potential association with hypergastrinemia
      induced by proton pump inhibitor administration. Previous confusion regarding
      diagnosis and therapy has been diminished by a series of international consensus
      statements defining the biology and management strategies for the disease.
      Overall, gastric NETs are categorized as well-differentiated or poorly
      differentiated neoplasms. Well-differentiated gastric NETs are enterochromaffin
      like (ECL) cell tumors subclassified into three types based on their relationship
      to gastrin, a key regulator of ECL cell neoplastic transformation. The treatment
      of type 1 and type 2 tumors depends on the size and invasiveness of the tumor,
      whereas type 3 tumors and poorly differentiated neuroendocrine carcinomas warrant
      aggressive surgical resection. The disease-specific 5-year survival ranges from
      about 95% in type 1 gastric carcinoids to about 25% in poorly differentiated
      gastric NECs. Elucidation of the precise biology of a gastric NET is critical to
      diagnosis and delineation of a type-specific management strategy.

PMID- 21080246
TI  - Management of refractory ascites and hepatorenal syndrome.
AB  - One of the most common manifestations of the development of portal hypertension
      in the patient with cirrhosis is the appearance of ascites. Once ascites
      develops, the prognosis worsens and the patient becomes susceptible to
      complications such as bacterial peritonitis, hepatic hydrothorax, hyponatremia,
      and complications of diuretic therapy. As the liver disease progresses, the
      ascites becomes more difficult to treat and many patients develop renal failure.
      Most patients can be managed by diuretics which, when used correctly, will
      control the ascites. Spontaneous bacterial peritonitis can be treated
      effectively, but portends a worse prognosis. Once the ascites becomes refractory
      to diuretics, liver transplantation is the best option, although use of
      transjugular intrahepatic portosystemic shunts will control the ascites in many
      patients. Lastly, the development of hepatorenal syndrome indicates the patient's
      liver disease is advanced, and transplantation again is the best option. However,
      use of vasoconstrictors may improve renal function in some patients, helping in
      their management while they await a liver transplant.

PMID- 21080248
TI  - Metastatic adenocarcinoma of the colon: early manifestation in gingival tissue.
AB  - A case of gingival metastasis of adenocarcinoma of the colon is reported, the
      lesion being an early clinical indication of a primary malignant tumor. The
      diagnosis of metastatic lesion in the oral region is always challenging, both to
      clinician and to the pathologist, due to its rarity and complexity. In the
      present case, the clinical hypothesis was peripheral ossifying fibroma or
      pyogenic granuloma. Histologically, the biopsy tissue revealed a malignant
      neoplasm not connected to the mucosal surface. Immunohistochemically, the lesion
      was positive for 35betaH11 and cytokeratin 20 and focally positive for
      cytokeratin 7. Treatment involved excision of primary tumor and follow-up
      chemotherapy. The clinical, histological and immunohistochemical characteristics
      are discussed.

PMID- 21080247
TI  - Quality of care in inflammatory bowel disease.
AB  - Advances in the treatment of inflammatory bowel disease (IBD) are published
      routinely in medical journals. Some treatments are sufficiently helpful that
      their conclusions are incorporated into clinical guidelines. However, such
      publications and proclamations may go unheeded among practitioners. Underuse,
      overuse, and misuse of clinical therapeutics, diagnostics, and routine medical
      processes are sufficiently prevalent among IBD practitioners that movements are
      afoot to determine the best methods for achieving a minimal uniformity of
      effective care. Such explorations are part of an effort to improve the quality of
      care. In this article, we review the background that has led to a push toward
      quality improvements in medicine in general, in gastroenterology in general, and
      within IBD specifically.

PMID- 21080249
TI  - Lasofoxifene in osteoporosis and its place in therapy.
AB  - Selective estrogen-receptor modulators (SERMs), which have estrogen-like effects
      on bone and "antiestrogen effects" on other tissues, have been in development for
      osteoporosis prevention and treatment in postmenopausal women as a safer
      alternative to long-term estrogen. We conducted a literature review of the
      skeletal and extraskeletal effects of lasofoxifene, a new generation SERM
      approved by the European Commission for osteoporosis treatment. Published data on
      the effects of lasofoxifene are based on 23 clinical pharmacology studies with
      over 10,000 participants from 17 phase 2 and 3 randomized controlled trials
      (RCTs). In RCTs, lasofoxifene decreases bone turnover markers (BTMs), increases
      bone mineral density (BMD) at the spine and hip, and decreases the incidence of
      vertebral and nonvertebral nonhip fractures compared with placebo. Compared with
      raloxifene, lasofoxifene gave greater decreases in BTMs, and greater increases in
      lumbar spine BMD. Lasofoxifene also decreased the risk of breast cancer, major
      coronary heart disease events, and stroke, but-similar to raloxifene-there was an
      increased risk of venous thromboembolism. In one trial, endometrial hypertrophy
      and uterine polyps were more common with lasofoxifene than with placebo, but
      endometrial cancer and hyperplasia were not. Lasofoxifene is probably most
      appropriate for use among women in their early or middle menopausal years (age 55
      65) who have, or are at risk of developing, osteoporosis and in particular
      vertebral fractures. At the time of publication, lasofoxifene is not approved for
      use by the US Food and Drug Administration, and as such is not used in North
      America.

PMID- 21080250
TI  - Concerns about exercise are related to walk test results in pulmonary
      rehabilitation for patients with COPD.
AB  - BACKGROUND: Although international guidelines on pulmonary rehabilitation
      acknowledge that psychological factors contribute to exercise intolerance in
      patients with chronic obstructive pulmonary disease (COPD), the few empirical
      studies investigating this association have found inconsistent results. PURPOSE:
      The purpose of this study is to investigate whether negative affect and beliefs
      about exercise of patients with COPD would be related to baseline 6-min walk (6
      MW) test results in a pulmonary rehabilitation setting, after correction for
      physical variables (sex, age, height, weight, and lung function). A second aim
      was to examine whether patients' beliefs are associated with treatment outcomes,
      as measured by an improvement in 6-MW distance. METHOD: A 12-week pulmonary
      rehabilitation program was completed by 166 patients. Beliefs (perceived
      necessity and concerns) about exercise and negative affect were assessed by a
      questionnaire. Clinical data were obtained from medical records. RESULTS:
      Baseline 6-MW distance was positively related to younger age, male gender, better
      pulmonary function, and having fewer concerns about exercise. After
      rehabilitation, patients had increased their walk distance by 12% (32 m), on
      average. Baseline physiological and psychological variables were unrelated to
      patients' response to treatment (increase in walk distance). However, subgroup
      analysis showed that for patients with mild to moderate airflow obstruction,
      concerns about exercise were negatively related to response to treatment.
      CONCLUSION: We conclude that patients' beliefs about the negative consequences of
      exercise are associated with baseline 6-MW test performance and response to
      treatment for patients with mild to moderate COPD. We recommend that patients'
      concerns about exercise are discussed and, if necessary, corrected during the
      intake phase.

PMID- 21080251
TI  - Genetic mutations of p53 and k-ras in gastric carcinoma patients from Hunan,
      China.
AB  - This case-control study investigated the mutations in p53 and k-ras genes of 123
      gastric carcinoma patients and 129 normal individuals from Hunan, China. By
      isolating genomic DNA from peripheral blood and employing polymerase chain
      reaction-single strand conformation polymorphism and DNA sequencing, the
      mutations of p53 exons-5, 6, 7, and 8 and k-ras were detected. The overall
      mutation frequency of p53 was 29.3%, and mutation was found in all four exons
      studied. The point mutations were predominant and among them, G:C->A:T was the
      highest (41.7%), followed by A:T->G:C (25%), G:C->C:G (11.1%), G:C->T:A (8.3%),
      and A:T->T:A (2.8%). The frameshift mutation was 11.1%. Mutations were detected
      in codons-131, 132, 133, 135, 149, 151, 162, 167, 173, 174, and 175 of exon 5,
      codons-193, 197, 213, and 215 of exon 6, codons-245, 246, 248, 249, and 270 of
      exon 7, and codons-271, 272, 273, and 282 of exon 8 of p53. The overall frequency
      of mutation in k-ras was 9.8%, mostly in codon-12 (91.7%) and in codon-13 (8.3%).
      There was no significant relationship between p53 and k-ras gene mutation in
      gastric carcinoma patients. Also, the relationships between p53 mutation and age,
      sex, smoking or drinking, and tumor metastasis were not significant. However, the
      patients with high/high-middle differentiated gastric carcinoma had a higher
      association with of p53 mutations. This study identified some novel p53 mutations
      in gastric cancer and showed mutation pattern and frequency of p53 and k-ras in
      the population of the central southern region of China.

PMID- 21080252
TI  - Modification of the L1-CAM carboxy-terminus in pancreatic adenocarcinoma cells.
AB  - The neural cell adhesion molecule L1 has recently been shown to be expressed in
      pancreatic adenocarcinoma (PDAC) cells. In this report, we demonstrate that L1 is
      expressed by moderately- to poorly-differentiated PDAC cells in situ, and that L1
      expression is a predictor of poor patient survival. In vitro, reduced reactivity
      of an anti-L1 carboxy-terminus-specific antibody was observed in the more poorly
      differentiated fast-growing (FG) variant of the COLO357 population, versus its
      well-differentiated slow-growing (SG) counterpart, even though they express
      equivalent total L1. The carboxy-terminus of L1 mediates binding to the MAP
      kinase-regulating protein RanBPM and mutation of T1247/S1248 within this region
      attenuates the expression of malignancy associated proteins and L1-induced
      tumorigenicity in mice. Therefore, we reasoned that the differential epitope
      exposure observed might be indicative of modifications responsible for regulating
      these events. However, epitope mapping demonstrated that the major determinant of
      binding was actually N1251; mutation of T1247 and S1248, alone or together, had
      little effect on C20 binding. Moreover, cluster assays using CD25 ectodomain/L1
      cytoplasmic domain chimeras demonstrated the N1251-dependent, RanBPM-independent
      stimulation of erk phosphorylation in these cells. Reactivity of this antibody
      also reflects the differential exposure of extracellular epitopes in these
      COLO357 sublines, consistent with the previous demonstration of L1 ectodomain
      conformation modulation by intracellular modifications. These data further
      support a central role for L1 in PDAC, and define a specific role for carboxy
      terminal residues including N1251 in the regulation of L1 activity in PDAC cells.

PMID- 21080254
TI  - Gradient and sensitivity enhanced multiple-quantum coherence in heteronuclear
      multidimensional NMR experiments.
AB  - Recent studies have indicated that the relaxation rate of the (1)H-(13)C multiple
      quantum coherence is much slower than that of the (1)H-(13)C single-quantum
      coherence for non-aromatic methine sites in (13) C labeled proteins and in
      nucleic acids at the slow tumbling limit. Several heteronuclear experiments have
      been designed to use a multiple-quantum coherence transfer scheme instead of the
      single-quantum transfer method, thereby increasing the sensitivity and resolution
      of the spectra. Here, we report a constant time, gradient and sensitivity
      enhanced HMQC experiment (CT-g/s-HMQC) and demonstrate that it has a significant
      sensitivity enhancement over constant time HMQC and constant time gradient and
      sensitivity enhanced HSQC experiments (CT-g/s-HSQC) when applied to a (13)C and
      (15) N labeled calmodulin sample in D(2)O. We also apply this approach to 3D
      NOESY-HMQC and doubly sensitivity enhanced TOCSY-HMQC experiments, and
      demonstrate that they are more sensitive than their HSQC counterparts.

PMID- 21080253
TI  - Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate.
AB  - Elevated levels of D: -2-hydroxyglutarate (D: -2-HG) occur in gliomas and myeloid
      leukemias associated with mutations of IDH1 and IDH2. L: -2-Hydroxyglutaric
      aciduria, an inherited metabolic disorder, predisposes to brain tumors.
      Therefore, we asked whether sporadic cancers, without IDH1 or IDH2 hot-spot
      mutations, show elevated 2-hydroxyglutarate levels. We retrieved 15 pairs of
      frozen papillary thyroid carcinoma (PTC) and adjacent non-neoplastic thyroid, and
      14 pairs of hyperplastic nodule (HN) and adjacent non-hyperplastic thyroid. In
      all lesions, exon 4 sequencing confirmed the absence of known mutations of IDH1
      and IDH2. We measured 2-hydroxyglutarate by liquid chromatography-tandem mass
      spectrometry. Compared to normal thyroid, PTCs had significantly higher D: -2-HG
      and L: -2-hydroxyglutarate (L: -2-HG) levels, and compared to HNs, PTCs had
      significantly higher D: -2-HG levels. D: -2-HG/L: -2-HG levels were not
      significantly different between HNs and normal thyroid. Further studies should
      clarify if elevated 2-hydroxyglutarate in PTC may be useful as cancer biomarker
      and evaluate the role of 2-hydroxyglutarate in cancer biology.

PMID- 21080255
TI  - A high-resolution HCANH experiment with enhanced sensitivity via multiple quantum
      line narrowing.
AB  - We report a 3D constant-time HCANH experiment (CTSL-HCANH) that uses the slower
      relaxation of multiple-quantum coherence to increase sensitivity and provides
      high C(alpha) resolution. In this experiment the H(alpha) of the (H(alpha),
      C(alpha)) multiple quanta are selectively spin locked, so that H(alpha) chemical
      shift evolution and (1) H-(1)H J-dephasing become ineffective during the
      relatively long delay needed for C(alpha) to N coherence transfer. As compared to
      an HCANH experiment that uses C(alpha) single-quantum coherence, an average
      enhancement of 20% was observed on calmodulin in complex with the binding domain
      of the transcription factor SEF2-1. Compared to CBCANH the signal intensity is
      approximately twice as good. The favorable relaxation properties of multiple
      quanta, together with the outstanding C(alpha) resolution, make the experiment a
      very good complement to CBCANH and CBCA(CO)NH for sequential assignment of larger
      proteins for which deuteration is not yet necessary.

PMID- 21080256
TI  - Induced alignment and measurement of dipolar couplings of an SH2 domain through
      direct binding with filamentous phage.
AB  - Large residual (15)N-(1)H dipolar couplings have been measured in a Src homology
      II domain aligned at Pf1 bacteriophage concentrations an order of magnitude lower
      than used for induction of a similar degree of alignment of nucleic acids and
      highly acidic proteins. An increase in (1) H and (15)N protein linewidths and a
      decrease in T(2) and T(1)rho relaxation time constants implicates a binding
      interaction between the protein and phage as the mechanism of alignment. However,
      the associated increased linewidth does not preclude the accurate measurement of
      large dipolar couplings in the aligned protein. A good correlation is observed
      between measured dipolar couplings and predicted values based on the high
      resolution NMR structure of the SH2 domain. The observation of binding-induced
      protein alignment promises to broaden the scope of alignment techniques by
      extending their applicability to proteins that are able to interact weakly with
      the alignment medium.

PMID- 21080258
TI  - Editorial.

PMID- 21080257
TI  - Letter to the Editor: Backbone NMR assignments of a cyanobacterial
      transcriptional factor, SmtB, that binds zinc ions.

PMID- 21080259
TI  - Improved 1HN-detected triple resonance TROSY-based experiments.
AB  - A pulse scheme resulting in improved sensitivity in TROSY-based 1HN-detected
      triple resonance experiments is presented. The approach minimizes relaxation
      losses which occur during the transfer of transverse magnetization from 15N to
      1HN immediately prior to detection. The utility of the method is demonstrated on
      a complex of methyl protonated, highly deuterated maltose binding protein (MBP,
      370 residues) and beta- cyclodextrin. Sensitivity gains relative to previous
      TROSY schemes of approximately 10 and 20% are noted in HNCO spectra of MBP
      recorded at 25 and 5  degrees C, respectively, corresponding to molecular
      correlation times of 23 and 46 ns.

PMID- 21080260
TI  - Determination of the relative NH proton lifetimes of the peptide analogue
      viomycin in aqueous solution by NMR-based diffusion measurement.
AB  - In aqueous solution, exchanging peptide NH protons experience two environments,
      that of the peptide itself with a relatively slow diffusion coefficient and that
      of the water solvent with a faster diffusion coefficient. Although in slow
      exchange on the NMR chemical shift timescale, the magnetic field gradient
      dependence of the NH peak intensities in an experiment used to measure diffusion
      coefficients reflects the relative time periods spent in the two environments and
      this allows the determination of the relative solvent accessibility of
      exchangeable protons in peptides or proteins. To test this approach, the magnetic
      field gradient dependent intensities of the chemically shifted amide and amine NH
      protons of the peptide antibiotic viomycin have been measured using the high
      resolution longitudinal-eddy-current-delay (LED) NMR method incorporating solvent
      water peak elimination by non-excitation. The NH resonances of viomycin have been
      assigned previously and their relative exchange rates determined. Here, the
      gradient dependence of each NH proton intensity is reported, and these, after a
      bi- exponential least squares fitting, yield the fractional lifetimes of the
      protons spent in the peptide and water environments during the diffusion period
      of the experiment.

PMID- 21080261
TI  - Mapping of the detergent-exposed surface of membrane proteins and peptides by 1H
      solution NMR in detergent: Application to the gramicidin A ion channel.
AB  - The present work evaluates the use of intermolecular polypeptide-detergent 1H
      through-space connectivities to determine the bilayer exposed-surface and the
      bilayer topography of membrane polypeptides solubilized in non- deuterated
      detergents. For this purpose, the membrane peptide gramicidin A, solubilized in
      non-deuterated sodium dodecylsulfate as its dimeric beta6,3 helix channel
      conformation was used. For this peptide, a high-resolution 3D structure, as well
      as reasonable assumptions concerning its membrane arrangement, exist. Band
      selective 2D NOESY, ROESY and 3D NOESY-NOESY experiments were used to detect
      detergent-polypeptide through-space correlations in the presence of an excess of
      the non-deuterated detergent. The observed intermolecular NOEs appear to be
      strongly temperature- dependent. Based on the known 3D structure of the
      gramicidin channel, the detergent-polypeptide through-space correlations appear
      to be selective for 1H located on the hydrophobic surface of gramicidin A with
      very few contributions from interior 1H or water-exposed 1H. It is suggested that
      this method can be of general use to evaluate the bilayer-exposed surface and
      topography of membrane peptides and small proteins.

PMID- 21080262
TI  - Half-filter experiments for assignment, structure determination and hydration
      analysis of unlabelled ligands bound to 13C/15N labelled proteins.
AB  - A novel variant of the 13C/15N omega2 half-filter experiment is reported for
      studying the hydration of an unlabelled ligand bound to a 15N and 13C uniformly
      labelled biological macromolecule. This doubly tuned filter experiment represents
      a powerful tool for obtaining resonance assignments, structure determination and
      hydration properties of a ligand. Its application to the binary complex formed by
      the inserted-domain (I-domain) of the leukocyte function-associated antigen-1
      (LFA-1) with a ligand reveals the presence of H2O molecules at the binding
      interface.

PMID- 21080263
TI  - Normalized one-dimensional NOE measurements in isotopically labeled
      macromolecules using two-way cross-polarization.
AB  - A novel one-dimensional NOE experiment is presented where a selected proton is
      excited by two-way heteronuclear cross- polarization between protons and nitrogen
      15 or carbon-13. The utility of the method is demonstrated for a sample of 15N
      labeled human ubiquitin. Inter- and intra-residue NOEs are clearly observed in a
      very time-effective manner. The signal intensities can be easily normalized.

PMID- 21080264
TI  - Band-selective editing of exchange-relay in protein-water NOE experiments.
AB  - A pulse sequence is proposed which uses a train of band-selective pulses for the
      editing of slow chemical exchange-relay effects in experiments designed to study
      water-macromolecule interactions. Compared to previous methods, this experiment
      does not require knowledge of the exact chemical shift of the relaying labile
      protons and needs only the recording of a single experiment to edit the relay
      through different exchanging groups resonating at different frequencies. The
      pulse sequence has been implemented using Gaussian cascades and was applied to
      the study of the hydration of HEW lysozyme.

PMID- 21080265
TI  - Water-protein NOEs: Optimized scheme for selective water excitation.
AB  - An alternative scheme for selective water excitation is proposed. The pulse
      sequence saturates the resonances from the solute, allowing the observation of
      water-solute NOEs with low artifact levels. The water resonance is subsequently
      excited by a relatively non-selective 90 degrees  pulse. The scheme is compared
      to other selective water excitation schemes. 2D NOE-NOESY and ROE-NOESY pulse
      sequences are proposed which afford high sensitivity by efficient water
      excitation and flip-back by radiation damping, yet allow the use of short mixing
      times for the buildup of water-solute NOEs.

PMID- 21080266
TI  - Gradient and sensitivity enhancement of 2D TROSY with water flip-back, 3D NOESY
      TROSY and TOCSY-TROSY experiments.
AB  - Previously we demonstrated a sensitivity enhancement of the original TROSY
      experiment by a factor of [Formula: see text] by the use of the sensitivity
      enhanced TROSY (en-TROSY) scheme. Here, we develop a gradient and sensitivity
      enhanced TROSY experiment (gs-TROSY), which is designed to select magnetization
      transfer pathways that suppress spectral artifacts and reduce the number of
      required phase cycles while having minimal loss of sensitivity. Both of these
      experimental methods (en-TROSY and gs- TROSY) have been combined with a water
      flip-back scheme which provides a further increase in sensitivity for labile NH
      groups by avoiding water saturation. We also apply these TROSY schemes to 3D
      NOESY-TROSY and 3D TOCSY-TROSY experiments.

PMID- 21080267
TI  - Reduced spectral density mapping for proteins: Validity for studies of 13C
      relaxation.
AB  - Spectral density mapping provides direct access to protein dynamics with no
      assumptions as to the nature of the molecule or its dynamic behaviour. Reduced
      spectral density mapping characterises a protein's motions at a lower
      experimental burden, assuming that the spectral density function J(omega) is flat
      around omegaH. This introduces little error for 15N relaxation data but is less
      valid for 13C studies, perturbing J(omegaC) considerably to an extent that
      depends on the nature of the molecule's motions. We propose the fitting of
      spectral density at high frequencies to a single Lorentzian and show that the
      true values of the spectral density lie between those determined by the two
      approximations.

PMID- 21080268
TI  - Letter to the Editor: 1H, 13C and 15N backbone resonance assignment of
      Escherichia coli adenylate kinase, a 23.6 kDa protein.

PMID- 21080270
TI  - [Venalpina VI: Phlebology training week, 23-30 January 2010, Pontresina, Engadin,
      Switzerland. Abstracts].

PMID- 21080269
TI  - [Principles and method of action of targeted therapies].
AB  - Conventional cytotoxic therapy is usually characterized by low specificity and
      considerable side effects. Targeted therapy, by contrast, allows for a specific
      inhibition with an acceptable side effect profile. A prerequisite for the
      development of such a therapy, however, is the identification and
      characterization of the molecular mechanisms that lead to tumor growth. Antibody
      based targeted therapies usually attack cell membrane-bound or extracellular
      proteins, while tyrosin kinase inhibitors usually act at intracellular domains of
      transmembranous proteins. Both strategies ultimately lead to an inhibition of the
      signal transduction cascade and thereby block increased cell proliferation,
      metastasis, or the production of new blood or lymph vessels.

PMID- 21080271
TI  - Introduction: Strategies for developing genetically modified mice.
AB  - Advancements in transgenic technologies have made the mouse one of the most
      useful animal models for biomedical research. Several technological breakthroughs
      have allowed the generation transgenic and knockout mouse models some 25 years
      ago. Subsequently, the technology has undergone many improvements, advancing our
      ability to control the expression of the genes and determine the cell types where
      the genetic modification should take place. Hence, the mouse is unique in
      offering the possibility to understand genotype-phenotype relationships that are
      relevant for unraveling the biological role of these genes in the human. This
      chapter provides an introductory overview.

PMID- 21080272
TI  - Genetic modification of the mouse: general technology - pronuclear and blastocyst
      injection.
AB  - Introduction of germ line mutations in mice via genetic engineering involves
      alterations of the structure and characteristics of genes. These alterations are
      mostly introduced via molecular genetic technology either in embryonal stem cells
      or in one-cell stage embryos. This chapter describes classic biotechnological
      methods used to generate mice from modified pre-implantation embryos.

PMID- 21080273
TI  - Generation of chimeras by aggregation of embryonic stem cells with diploid or
      tetraploid mouse embryos.
AB  - From the hybrid creatures of the Greek and Egyptian mythologies, the concept of
      the chimera has evolved and, in modern day biology, refers to an organism
      comprises of at least two populations of genetically distinct cells. Mouse
      chimeras have proven an invaluable tool for the generation of genetically
      modified strains. In addition, chimeras have been extensively used in
      developmental biology as a powerful tool to analyze the phenotype of specific
      mutations, to attribute function to gene products and to address the question of
      cell autonomy versus noncell autonomy of gene function. This chapter describes a
      simple and economical technique used to generate mouse chimeras by embryo
      aggregation. Multiple aggregation combinations are described each of which can be
      tailored to answer particular biological questions.

PMID- 21080274
TI  - Cryopreservation of mouse spermatozoa and in vitro fertilization.
AB  - Cryopreservation of mouse spermatozoa has become the foremost technique for
      preserving large numbers of different strains of mice with induced mutations.
      Recently, we have established procedures for cryopreservation of mouse
      spermatozoa and in vitro fertilization using cryopreserved spermatozoa to obtain
      a relatively high fertilization rate. This chapter attempts to show these
      procedures in simple terms.

PMID- 21080275
TI  - Autopsy and histological analysis of the transgenic mouse.
AB  - Over the past decades, transgenic and knock-out mouse models have become common
      use in research laboratories. Detailed phenotypic characterization of such models
      is essential for understanding basic mechanisms of normal physiology and disease.
      Hereto, pathological examination is a very helpful tool. This chapter describes
      detailed procedures to perform autopsy and immuno-histological analysis of mice.

PMID- 21080276
TI  - Transgene design.
AB  - Transgenics are powerful mouse models to understand the biological functions of
      genes. This chapter gives a short overview of the requirements and considerations
      in designing a transgene. In addition, potential important choices that have to
      be made in advance for the successful designing and generating a transgenic mouse
      model are discussed. Methods for DNA purification for microinjection are also
      provided in this chapter.

PMID- 21080277
TI  - Inducible transgenic mouse models.
AB  - Inducible transgenic mouse models allow for the activation of genes in specific
      cells and tissues at specific times. Expression levels are dependent on the dose
      of the agent administered. Effective experimental models are characterized by low
      background levels of the regulated gene and induction to high levels with sub
      physiological levels of inducing agents. The most commonly used methods to
      control gene expression in mouse models are based on the tet-operon/repressor bi
      transgenic system and the estrogen receptor (ER) ligand-binding domain. Less
      commonly used systems to control gene expression in transgenic mice take
      advantage of the ligand-binding domain of the progesterone receptor, and the lac
      and GAL4 inducible systems. The tetracycline-regulated transgenic models are
      typically designed to activate the expression of the gene of interest in a
      specific cell type at a specific point in time. The ER is most commonly fused
      with Cre recombinase, although it can be used with transcription factors,
      kinases, etc., that are active in the nucleus. Cre-ER transgenes allow for the
      induction of recombinase activity in specific cells at defined time points. Cre
      recombinase is most often found in combination with conditional alleles to
      inactivate gene expression. When used for gene activation, Cre removes stop
      cassettes from transgenes and thus allows the expression of reporter or other
      molecules. Thus, the tetracycline-regulated and Cre-ER systems are complementary
      in mouse models, with utility in the cell-specific activation and inactivation of
      gene expression.

PMID- 21080278
TI  - Lentiviral transgenesis.
AB  - Conventional DNA injection-based methods are successful in generating transgenic
      animals and have remained nearly unchanged over the last few decades. Lentiviral
      vectors are alternative powerful tool for generating transgenic animals, in part
      because of their ability to incorporate into genomic DNA with high efficiency.
      This chapter describes lentiviral vectors used to generate transgenic mice and
      rats. We discuss the protocols and methods in high enough detail such that
      researchers who are accustomed to creating transgenic animals by pronuclear
      injection can smoothly transition to using lentiviral transgenesis. We will
      briefly outline the general principle of the lentiviral expression system and
      focus specifically on the methods used to generate lentiviral vectors, produce
      lentiviral particles, inject lentivirus into the fertilized oocytes, and
      transplant them into the pseudopregnant females. In addition to the surgical
      aspects of the experiment, we will describe methods to produce high titer
      lentivirus. Finally, we will discuss the limitations of lentiviral transgenesis
      and summarize information that will be useful for troubleshooting.

PMID- 21080279
TI  - Transgenesis in mouse embryonic stem cells.
AB  - Traditionally, transgenic mice are generated by pronuclear injection of exogenous
      DNA. This technique has several limitations, including limited control over
      transgene expression, transgene cytotoxicity, -promiscuity and silencing, and
      founder mouse sterility. Here we describe two protocols to generate transgenic
      mice from ES cell clones carrying stably integrated exogenous DNA with inducible
      transgene expression.

PMID- 21080280
TI  - Engineering BAC reporter gene constructs for mouse transgenesis.
AB  - A culmination of large-scale ideas and efforts has truly allowed for the use of
      large genomic DNA clones housed in Bacterial Artificial Chromosome (BAC) vectors
      for biological research. Fundamental advances that have allowed this to happen
      include (1) the completion of genome sequencing projects and the establishment of
      highly annotated web-accessible databases allowing for the rapid identity and
      purchase of BAC clones containing genes of interest. (2) The generation of
      methodologies to modify BACs genetically, allowing for the rapid creation of gene
      targeting constructs or transgenic reporter gene constructs using homologous
      recombination in bacteria.Recent efforts on our part have capitalized on these
      advances by using BACs and bacterial recombination methods to generate
      fluorescent protein reporter transgenic mice to study skeletal biology. The
      rationale for using BAC genomic DNA clones to engineer reporter gene constructs
      is based on their much larger size, thus increasing the likelihood that most, if
      not all, of a gene's respective cis regulator elements are present, giving a
      truer representation of the endogenous gene's expression. In a relatively short
      amount of time, we have become extremely proficient at generating BAC reporters.
      Contrary to the widely perceived notion that working with BACs is complex and
      difficult, we decided to write this chapter to encourage laboratories that are
      currently using traditional molecular cloning methods to engineer transgenic DNA
      constructs to strongly consider learning BAC methodologies. As an example, we
      walk through the steps we took to generate the transgenic reporter mouse line,
      Tenascin C (TNC)-mCherry.

PMID- 21080281
TI  - Targeting vector construction through recombineering.
AB  - Gene targeting in mouse embryonic stem cells is an essential, yet still very
      expensive and highly time-consuming, tool and method to study gene function at
      the organismal level or to create mouse models of human diseases. Conventional
      cloning-based methods have been largely used for generating targeting vectors,
      but are hampered by a number of limiting factors, including the variety and
      location of restriction enzymes in the gene locus of interest, the specific PCR
      amplification of repetitive DNA sequences, and cloning of large DNA fragments.
      Recombineering is a technique that exploits the highly efficient homologous
      recombination function encoded by lambda phage in Escherichia coli. Bacteriophage
      based recombination can recombine homologous sequences as short as 30-50 bases,
      allowing manipulations such as insertion, deletion, or mutation of virtually any
      genomic region. The large availability of mouse genomic bacterial artificial
      chromosome (BAC) libraries covering most of the genome facilitates the retrieval
      of genomic DNA sequences from the bacterial chromosomes through recombineering.
      This chapter describes a successfully applied protocol and aims to be a detailed
      guide through the steps of generation of targeting vectors through
      recombineering.

PMID- 21080282
TI  - Generating conditional knockout mice.
AB  - Gene targeting in ES cells is extensively used to generate designed mouse mutants
      and to study gene function in vivo. Knockout mice that harbor a null allele in
      their germline provide appropriate genetic models of inherited diseases and often
      exhibit embryonic or early postnatal lethality. To study gene function in adult
      mice and in selected cell types, a refined strategy for conditional gene
      inactivation has been developed that relies on the DNA recombinase Cre and its
      recognition (loxP) sites. For conditional mutagenesis, a target gene is modified
      by the insertion of two loxP sites that enable to excise the flanked (floxed)
      gene segment through Cre-mediated recombination. Conditional mutant mice are
      obtained by crossing the floxed strain with a Cre transgenic line such that the
      target gene becomes inactivated in vivo within the expression domain of Cre. A
      large collection of Cre transgenic lines has been generated over time and can be
      used in a combinatorial manner to achieve gene inactivation in many different
      cell types. A growing number of CreER(T2) transgenic mice further allows for
      inducible inactivation of floxed alleles in adult mice upon administration of
      tamoxifen. This chapter covers the design and construction of loxP flanked
      alleles and refers to the vectors, ES cells, and mice generated by the European
      conditional mouse mutagenesis (EUCOMM) project. We further describe the design
      and use of Cre and CreER(T2) transgenic mice and a convenient breeding strategy
      to raise conditional mutants and controls for phenotype analysis.

PMID- 21080283
TI  - Hypomorphic mice.
AB  - The use of genetically engineered mice has become a standard approach in order to
      study the physiological contribution of genes in a variety of life-science
      disciplines. Classical and conditional gene-targeting methods aimed at generating
      knock-out mice that lack gene products have been useful, but may be limited in
      their scope. If the gene of interest is essential for cell viability, little
      insight can be gained into the in vivo function of these genes. A hypomorphic
      approach, utilizing many of the same methods employed for traditional gene
      targeting, allows one to disrupt the function of genes to a lesser degree and
      bypass the lethality caused by many gene mutations. The purpose of this chapter
      is to introduce the concepts behind how hypomorphic alleles impede normal genetic
      function and provide information necessary to construct a targeting vector
      successfully for use in ES cells to generate ultimately mice with lower than
      normal amounts of an endogenous protein of interest.

PMID- 21080284
TI  - MICER targeting vectors for manipulating the mouse genome.
AB  - The mouse has become an important model for understanding human development,
      physiology and disease because of its genetic and biological similarity to
      humans. Desired mouse mutants with precise genetic alterations can now be
      generated through gene targeting in mouse embryonic stem cells. The rate-limiting
      factor in a gene-targeting experiment is the time needed for cloning to construct
      targeting vectors. The establishment of the Mutagenic Insertion and Chromosome
      Engineering Resource has made available targeting vectors for the insertional
      mutagenesis of a large number of mouse genes as well as for chromosome
      engineering throughout the mouse genome. This unique resource has enriched the
      repertoire of the genetic reagents for targeted manipulation of the mouse genome.

PMID- 21080285
TI  - Knock-in approaches.
AB  - Molecular genetic strategies to study gene function in mice or to generate a
      mouse model for a human disease are continuously under development. The
      application and importance of knock-in approaches are increasing. This chapter
      elaborates on novel developments for the generation of knock-in mice. Special
      emphasis is given to recombinase-mediated cassette exchange, a new emerging knock
      in strategy that enables easy generation of a series of different knock-in
      mutations within one gene.

PMID- 21080286
TI  - Generation of a series of knock-in alleles using RMCE in ES cells.
AB  - Recombinase-mediated cassette exchange (RMCE) is a powerful tool to generate a
      series of knock-in mutations into a particular gene of the mouse. It uses
      standard ES cell technologies to introduce an exchangeable cassette into the gene
      of interest by homologous recombination. Because the introduced exchangeable
      cassette is flanked by heterotypic specific recombination target sequences, site
      specific recombinases can be used in a subsequent RMCE step to exchange the
      cassette by other sequences. Here, an experimental procedure for the application
      of RMCE in E14 ES cells using heterotypic FRT recombination target sequences and
      the site-specific recombinase Flp is elaborated.

PMID- 21080287
TI  - Selection of targeted mutants from a library of randomly mutagenized ES cells.
AB  - A method for random relatively unbiased mutagenesis of ES cells with a mutagenic
      retroviral vector is described. An orderly assembly of mutant ES cells in multi
      well plates is generated. 3D pooling of the wells of the assembly allows quick
      PCR search for insertions in genes of interest. Mutant ES cell clones are then
      isolated from the positive wells and used to produce mutant animals using
      conventional techniques.

PMID- 21080288
TI  - Generation of genetically modified rodents using random ENU mutagenesis.
AB  - The generation of genetically modified animals using N-ethyl-N-nitrosourea (ENU)
      mutagenesis is a fast and highly effective method. The technique is based on
      treating male animals with the supermutagen ENU, which randomly introduces
      mutations in the spermatogonial stem cells. By breeding these animals with
      untreated females, an F1 population is generated in which each individual carries
      unique random ENU-induced mutations, which can be retrieved using either genotype
      driven or phenotype-driven approaches. No complicated cell culturing techniques
      are required and since no foreign DNA is introduced, the mutant animals that are
      generated are not transgenic. Here, we describe the detailed protocols for ENU
      mutagenesis and for mutant retrieval.

PMID- 21080289
TI  - Bone marrow transplantations to study gene function in hematopoietic cells.
AB  - Immune cells are derived from hematopoietic stem cells in the bone marrow.
      Experimental replacement of bone marrow offers the unique possibility to replace
      immune cells, to study gene function in mouse models of disease. Over the past
      decades, this technique has been used extensively to study, for instance,
      macrophage function in atherosclerosis. In this chapter, we describe the methods
      for both full bone marrow transplantations and T cell-specific transfers.

PMID- 21080290
TI  - Adenovirus-mediated gene transfer.
AB  - Recombinant adenoviruses are attractive vectors for short-term expression in
      mouse liver and primary cell lines. Various versatile vector systems have been
      developed which can be used for the reliable production of recombinant
      adenoviruses. This protocol describes the entire process for the production of
      recombinant adenoviruses using the AdEasy system. This protocol will give a
      practical step-by-step description from the cloning of the gene of interest until
      the in vivo administration in mice. The entire process will take about 8 weeks to
      complete.

PMID- 21080292
TI  - Becoming an effective clinician for people who stutter: what do you need to know?

PMID- 21080293
TI  - Evidence of clinically significant change: the therapeutic alliance and the
      possibilities of outcomes-informed care.
AB  - This article addresses the issue of clinically significant (or meaningful) change
      resulting from treatment for stuttering. Research in both medical and behavioral
      fields indicates that clients often have their own unique perspective of
      meaningful clinical change and that this perspective is often different from that
      of the professional administering the treatment. Among the variables that the
      client brings to the treatment session are their progression through stages of
      therapeutic change and the ways in which they believe they are capable of coping
      with their problem. Research has shown that how an individual interprets the
      meaning his or her therapeutic experience is central to clinically significant
      change. Procedures for obtaining feedback from clients concerning clinically
      significant change and the quality of the therapeutic alliance are described.

PMID- 21080294
TI  - Empathy: perhaps the most important E in EBP.
AB  - Treatment of stuttering has recently been influenced by calls for evidence-based
      practice. Unfortunately, most of the existing treatment "evidence" in stuttering
      focuses on the surface behaviors of the disorder. Although these behaviors are an
      important part of the problem of stuttering, they may not be the most critical
      factor to the person who stutters. This article discusses loss of control as the
      critical factor in stuttering and examines historical and practical reasons why
      this part of the disorder has been largely ignored in research about stuttering
      and stuttering treatment. Suggestions for viewing stuttering from the perspective
      of the client and the importance of taking this perspective are provided.

PMID- 21080295
TI  - What the literature tells us about listeners' reactions to stuttering:
      implications for the clinical management of stuttering.
AB  - It is known that listeners harbor negative stereotypes toward people who stutter
      but there are a host of other findings in the literature that provide a broader
      perspective about how listeners react to stuttering. The focus of this article is
      a discussion of four areas of research related to listener reactions to
      stuttering: (1) how stuttering impacts listeners' reactions to mild, moderate,
      and severe stuttering; (2) how stuttering interferes with listener recall and
      comprehension of story information; (3) how children react to stuttering; and (4)
      how listeners react to strategies plus use in stuttering therapy programs.
      Studies associated with these four areas of research are summarized and
      discussed. Clinical implications that emerge from these studies are described to
      assist clinicians in the treatment of children and adults who stutter.

PMID- 21080296
TI  - Translating recent research into meaningful clinical practice.
AB  - The goal of this article is to provide a synopsis of research, both basic and
      applied, that can improve the evaluation and treatment of stuttering in children
      and adults, as well as counseling of clients, families, and other professionals
      who interact with the person who stutters. Relevant basic research has informed
      genetic contributions to stuttering and possible neurological substrates of the
      disorder. Several treatment approaches to stuttering have recently been
      published, with varying degrees of apparent efficacy. There has also been
      increased attention to therapeutic outcomes that go beyond the components of the
      specific therapies themselves, which have the potential to improve therapy
      outcomes.

PMID- 21080297
TI  - Working with young children who stutter: raising our game.
AB  - Several therapy programs have been demonstrated to be effective in supporting the
      development of fluency in preschool children who stutter. However, there is
      increasing evidence in allied fields suggesting that a positive therapy outcome
      cannot be entirely attributed to the therapy program itself, but also depends on
      what the therapist brings to the therapeutic context. This article seeks to
      discuss the therapist's skills and attributes that play a part in the development
      of the therapeutic alliance, which underpins therapy involving parents of young
      children who stutter. Using a model of clinical expertise development, the
      article discusses the attributes and skills that are necessary for the
      development of expertise, along with the behavioral and cognitive changes that
      evolve as a therapist becomes increasingly expert at using one particular
      program, Palin Parent-Child Interaction Therapy.

PMID- 21080298
TI  - Evaluating and treating school-aged children who stutter.
AB  - School-based speech-language pathologists are often called upon to treat children
      who stutter, though many clinicians have reported that they feel uncomfortable
      working with this population. Fortunately, there is much that speech-language
      pathologists can do to help children who stutter speak more easily and minimize
      the adverse impact of stuttering in both academic and social settings. The
      purpose of this article is to provide clinicians with a guide to some of the key
      issues they should consider when working with school-aged children who stutter.
      The goal is to encourage clinicians to develop a better understanding of how
      stuttering can affect school-aged children, how the adverse effects of the
      disorder can be documented so children can be qualified for treatment, and,
      ultimately, how the negative consequences of stuttering can be minimized through
      a comprehensive approach to treatment.

PMID- 21080299
TI  - Stuttering treatment for adults: an update on contemporary approaches.
AB  - This article provides a brief overview of historical and current approaches to
      stuttering treatment for adults. Treatment is discussed in terms of stuttering
      management approaches, fluency-shaping approaches, and combined approaches. The
      evidence base for these various approaches is outlined. Fluency-shaping
      approaches have the most robust outcome evidence. Stuttering management
      approaches are based more on theoretical models of stuttering, and the evidence
      base tends to be inferred from work using the approaches of cognitive behavior
      therapy and desensitization with other disorders such as anxiety. Finally,
      comprehensive approaches to treating stuttering are discussed, and several
      clinical methods are outlined. Comprehensive approaches target both improved
      speech fluency and stuttering management. Although it is presented that a
      comprehensive approach to stuttering treatment will provide the best results, no
      single approach to stuttering treatment can claim universal success with all
      adults who stutter.

PMID- 21080300
TI  - Becoming an effective clinician for people who stutter: you can do it!

PMID- 21080301
TI  - A new classification for "pistol grip deformity" - correlation between the
      severity of the deformity and the grade of osteoarthritis of the hip.
AB  - PURPOSE: Two types of femoroacetabular impingement (FAI) are described as reasons
      for the early development of osteoarthritis of the hip. Cam impingement develops
      from contact between an abnormal head-neck junction and the acetabular rim.
      Pincer impingement is characterized by local or general overcoverage of the
      femoral head by the acetabular rim. Both forms might cause early osteoarthritis
      of the hip. A decreased head/neck offset has been recognized on AP pelvic views
      and labeled as "pistol grip deformity". The aim of the study was to develop a
      classification for this deformity with regard to the stage of osteoarthritis of
      the hip. MATERIALS AND METHODS: 76 pelvic and axial views were analyzed for alpha
      angle and head ratio. 22 of them had a normal shape in the head-neck region and
      no osteoarthritis signs, 27 had a "pistol grip deformity" and osteoarthritis I
      and 27 had a "pistol grip deformity" and osteoarthritis II degrees -IV degrees .
      The CART method was used to develop a classification. RESULTS: There was a
      statistically significant correlation between alpha angle and head ratio. A
      statistically significant difference in alpha angle and head ratio was seen
      between the three groups. Using the CART method, we developed a three-step
      classification system for the "pistol grip deformity" with very high accuracy.
      This deformity was aggravated by increasing age. CONCLUSION: Using this model it
      is possible to differentiate between normal shapes of the head-neck junction and
      different severities of the pistol grip deformity.

PMID- 21080302
TI  - [Micronodular sonographic pattern of the spleen: a frequent finding in children
      and adolescents].
AB  - In textbooks about abdominal sonography, the parenchyma of the spleen is
      described as homogeneous. However, using high-frequency probes, sonography of the
      spleen in children often reveals a micronodular pattern. AIM: To investigate the
      prevalence of a micronodular pattern in the pediatric spleen and to evaluate
      possible correlations to clinical parameters. METHODS: In 106 non-selected
      children (54 males, 52 females, mean age 7 years 10 months), the spleen was
      examined with a 17 MHz probe. Simultaneously the size of the spleen was measured,
      and other parameters such as leukocyte and thrombocyte counts were recorded. The
      pattern of the spleen was estimated using a four-step scale. 0: homogeneous
      tissue without micronodular components, 1: faint micronodular pattern/barely
      perceptible, 2 and 3: micronodular pattern clearly visible of moderate (2) or
      strong intensity (3). RESULTS: In 33 children a homogenous pattern was found
      (31.1 %) and in 48 children (45.3 %) a micronodular pattern of the spleen was
      clearly visible. A statistical correlation to spleen size or leukocyte or
      thrombocyte count or CRP could not be proven. 52 % of children with an enlarged
      spleen had a micronodular pattern, as well as 66.7 % of children with
      leukocytosis, 44.7 % of children with increased CRP, and 54.5 % of children with
      thrombocytosis. However, there was a strong statistical correlation to the age of
      the children with a maximum at the age of 1 to 5 years. CONCLUSION: A
      micronodular pattern of the spleen is frequent in children, even without clinical
      signs of infection. It is important to be aware of this finding and not to
      confuse it with pathological changes.

PMID- 21080303
TI  - Coronary artery calcium score: influence of the reconstruction interval on
      cardiac risk stratification in asymptomatic patients using dual-source computed
      tomography.
AB  - PURPOSE: To evaluate the impact of the reconstruction interval on coronary
      calcium score and cardiac risk stratification using dual-source computed
      tomography (DSCT). MATERIALS AND METHODS: DSCT coronary calcium scoring was
      performed in 61 consecutive patients, and five data sets per patient were
      reconstructed within diastole (50 - 70 % of the R-R interval). The Agatston
      score, volumetric score and the relative variability were assessed for all
      reconstructions. To assess the individual cardiovascular risk, patients were
      assigned to risk groups based on age and gender-matched percentile ranks.
      RESULTS: The mean Agatston score was 184.8 +/- 377.9 (relative variability 47 %
      +/- 52 %). The mean volumetric score was 164.4 +/- 310.1 (relative variability 49
      % +/- 58 %). There was a negative correlation between the total Agatston score
      and the relative variability (r = -0.37; p < 0.01). Depending on the
      reconstruction interval used, 18 predominantly young patients were assigned to
      more than one risk group. CONCLUSION: Despite the increased temporal resolution
      of DSCT examinations, the Agatston and volumetric scores depend on the
      reconstruction time within the cardiac cycle. The fact that the greatest relative
      variability for both the Agatston score and the volumetric score was found in
      young patients with small amounts of coronary calcium may result in different
      treatment strategies for young patients depending on the reconstruction used.
      Therefore, more accurate risk stratification may require the analysis of multiple
      reconstruction intervals.

PMID- 21080304
TI  - [Successful conservative therapy of an infected, percutaneously implanted,
      infrarenal aortic stent].

PMID- 21080305
TI  - Enhancement of TNF-alpha expression and inhibition of glucose uptake by nicotine
      in the presence of a free fatty acid in C2C12 skeletal myocytes.
AB  - Smoking is a risk factor for insulin resistance and metabolic syndrome. However,
      mechanisms responsible for smoking-induced insulin resistance are unclear. We
      examined the combined effect of nicotine, a toxic substance in tobacco smoke, and
      palmitate in the serum physiological concentration range on tumor necrosis factor
      alpha (TNF-alpha) expression and impairment of glucose uptake in C2C12 myotubes,
      since smokers do not have increased serum free fatty acid (FFA) concentrations
      with insulin resistance compared to nonsmokers. C2C12 myotubes were incubated for
      24 h with nicotine (1 MUmol/l) in the presence or absence of palmitate (200
      MUmol/l). RT-PCR and Western blotting showed increased TNF-alpha expression in
      C2C12 myotubes treated with nicotine in the presence of palmitate. Furthermore,
      stimulation with nicotine in the presence of palmitate enhanced the production of
      reactive oxygen species (ROS) and activated the protein kinase C-nuclear factor
      kappaB (PKC-NF-kappaB) pathway, as detected by dihydroethidium staining and
      Western blotting, respectively. Consequently, the translocation of GLUT4 to the
      plasma membrane as well as insulin-stimulated Akt phosphorylation was impaired,
      and glucose uptake to the myocytes was blocked. In addition, the production of
      ROS was suppressed by 4-hydroxy-TEMPO, and inhibition of GLUT4 translocation to
      the plasma membrane was canceled. These results suggest that in C2C12 myotubes,
      nicotine in the presence of palmitate enhanced the production of ROS and the
      expression of TNF-alpha through the PKC-NF-kappaB pathway; suppressed GLUT4
      translocation to the plasma membrane; and impaired glucose uptake to cells. This
      pathway represents a possible mechanism by which smoking induces insulin
      resistance in the body.

PMID- 21080306
TI  - Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the
      discrimination of solid pancreatic masses.
AB  - PURPOSE: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for the
      assessment of microcirculation and the delineation of pancreatic tumors in order
      to characterize and stage them has only recently become available for commercial
      use, and few reports have been published. The purpose of the study was the
      qualitative and quantitative digital image analysis of pancreatic adenocarcinomas
      using conventional endoscopic ultrasonography (EUS) and CEH-EUS and the
      evaluation of whether contrast medium injection modified adenocarcinoma staging
      and patient management. MATERIALS AND METHODS: In each of 30 prospectively
      examined patients with suspected pancreatic solid lesions, CEH-EUS was performed
      using the same quantity of the contrast agent SonoVue and a low mechanical index
      (0.3 - 0.4), followed by EUS-FNA. The histology, based on EUS-FNA or surgery and
      9 months of follow-up, was: pancreatic adenocarcinoma (n = 15), pseudotumoral
      chronic pancreatitis (n = 12), neuroendocrine tumor (n = 1), common bile duct
      tumor (n = 1), lymph node metastases of gastric cancer (n = 1). The quantitative
      analysis was based on histograms obtained from each CEH-EUS video recording.
      RESULTS: CEH-EUS showed a hypoenhanced pattern in 14 cases of adenocarcinoma and
      in 10 cases of chronic pancreatitis. The index of the contrast uptake ratio was
      significantly lower in adenocarcinoma than in mass-forming chronic pancreatitis.
      A cut-off uptake ratio index value of 0.17 for diagnosing adenocarcinoma
      corresponded to an AUC (CI 95%) of 0.86 (0.67 - 1.00) with a sensitivity of 80%,
      a specificity of 91.7%, a positive predictive value of 92.8%, and a negative
      predictive value of 78%. The size of the pancreatic mass was assessed
      significantly more effectively by CEH-EUS but adenocarcinoma staging was not
      modified. CONCLUSION: The majority of cases of both pancreatic adenocarcinoma and
      chronic pancreatitis were hypoenhanced and visual discrimination was not
      possible. This is the first study about CEH-EUS for the quantitative assessment
      of uptake after contrast injection which has shown that it can aid
      differentiation between benign and malignant masses but cannot replace EUS-FNA.
      Neither tumor stage nor therapeutic management have changed after contrast medium
      injection during CEH-EUS.

PMID- 21080307
TI  - Ultrasound guidance for neuraxial analgesia and anesthesia in obstetrics: a
      quantitative systematic review.
AB  - PURPOSE: The aim of this quantitative systematic review was to assess the
      efficacy and safety of ultrasound-guided neuraxial blocks in obstetric analgesia
      and anesthesia. MATERIALS AND METHODS: A systematic search for clinical trials
      investigating the efficacy and safety of ultrasound-assisted neuraxial blocks in
      comparison to any other technique was performed in MEDLINE, EMBASE, CINAHL and
      CENTRAL. Relative risks (RR) were calculated for dichotomous data (e. g. number
      of patients with vascular punctures), and mean differences (MD) were calculated
      for continuous outcomes (e. g. number puncture attempts), along with the
      respective 95 % confidence intervals (95 % CI). RESULTS: Six clinical trials
      (published between 2001 and 2009) including the data of 659 patients satisfied
      the inclusion criteria. Ultrasound-facilitated neuraxial blocks required a lower
      number of puncture attempts (MD: -0.92; 95 % CI: -1.11 to -0.74; p < 0.00001) and
      fewer puncture levels (MD: -0.2; 95 % CI: -0.31 to -0.1; p = 0.0002) in
      comparison with the more conventional loss of resistance. The success rate with
      the first attempt under ultrasound guidance in supposedly difficult patients was
      71 % in comparison to 20 % using a conventional technique. Patients receiving
      ultrasound-assisted neuraxial blocks had a lower rate of procedure-related
      complications (post-dural puncture headache, spinal or vascular puncture).
      CONCLUSION: There is some evidence that ultrasound guidance may improve the
      efficacy and safety of neuraxial blocks in obstetrics. If technical difficulties
      are anticipated, ultrasound may lower the rate of procedure-related adverse
      events.

PMID- 21080308
TI  - Multivariate analysis of flow data in breast lesions and validation in a normal
      clinical setting.
AB  - PURPOSE: To improve differentiation between benign and malignant breast lesions
      by Doppler measurements and to validate results in a normal clinical setting in
      comparison to study conditions. MATERIALS AND METHODS: Doppler measurements of
      458 patients were compared in benign and malignant tumors in a prospective study.
      In a multivariate analysis a diagnostic score was developed using a logistic
      regression model and stepwise selection. These results were compared with 272
      patients who were examined under routine clinical conditions. RESULTS: Most
      measurements showed highly significant (p < 0.001) differences between benign and
      malignant tumors. For each measurement we considered two cut-points to define a
      diagnostic rule. Despite significant differences, none of the corresponding
      classification rules exceeded 90 % sensitivity and specificity. Multivariate
      analysis selected a model including age and the number of arteries and
      contralateral arteries. Although significant, the last factor barely improved
      diagnostic accuracy. Therefore, we deleted it from the multivariate model. Based
      on a simple model including age and the number of tumor arteries, we defined
      classification rules with high sensitivity and specificity. The RI measurement
      did not improve the discriminatory power of our score. In the validation study
      the sensitivity decreased from 89 - 98 % to 58 - 78 % with a specificity of 82 -
      92 % vs. 83 - 86 %. CONCLUSION: Color Doppler can be used for breast cancer
      differentiation. However, in the clinical routine the sensitivity decreases
      considerably compared with optimized study conditions.

PMID- 21080309
TI  - New sonographic method for fetuses with a large abdominal circumference improves
      fetal weight estimation.
AB  - PURPOSE: Birth weight (BW) is an important prognostic parameter for neonatal
      morbidity and mortality. Commonly used weight formulas lack accuracy, especially
      at the lower and upper end of the fetal weight range. Fetal abdominal
      circumference (AC) as part of most of the commonly used equations has the
      greatest impact on weight estimation. It has been shown that formulas
      specifically designed for a small fetal AC can improve weight estimation. The aim
      was to find out whether a new formula specifically designed for fetuses with a
      large AC may also improve weight determination. MATERIALS AND METHODS: The study
      included 830 singleton pregnancies. The inclusion criteria were ultrasound
      examination with complete biometric parameters and an AC >= 36.0 cm within 7 days
      of delivery, and an absence of structural or chromosomal malformations. Two "best
      fit" formulas were derived by forward regression analysis. The accuracy of the
      new formulas was compared with commonly used weight equations using percentage
      error (PE), absolute percentage error (APE), limits of agreement (LOA) and
      cumulative distribution. RESULTS: New formula I had no systematic error while new
      formula II and the routine methods significantly overestimated fetal weight. The
      medians of the APE were the lowest among the new equations (5.77 and 7.25). The
      new formulas also demonstrated the narrowest LOA. Importantly, at all discrepancy
      levels (5 %, 10 %, 15 %, and 20 %), new formula I included significantly more
      cases than the commonly used methods. CONCLUSION: These specifically designed
      equations help to improve fetal weight estimation for fetuses with an AC >= 36.0
      cm. For optimal weight estimation, we recommend using new formula I.

PMID- 21080310
TI  - 3D volume contrast imaging (VCI) for the visualization of placenta previa increta
      and uterine wall thickness in a dichorionic twin pregnancy.
AB  - PURPOSE: Placenta increta is a rare event in pregnancy, but is associated with
      serious maternal morbidity and mortality due to life threatening hemorrhage. The
      incidence has increased due to high Cesarean rates. We describe a case of
      placenta previa increta in a dichorionic twin pregnancy, which was successfully
      treated conservatively, to discuss the role of ultrasound, especially 3D VCI and
      TUI, for diagnosis and conservative management in similar cases. MATERIALS AND
      METHODS: A GE Voluson Expert 730 ultrasound system which provides both
      conventional 2D imaging and 3D volume acquisitions using VCI and TUI was used for
      diagnosis and management in a case of placenta increta in a dichorionic twin
      pregnancy in which the placenta previa increta of the first fetus was left in
      situ and the other placenta was removed. RESULTS: The 3D VCI provided superior
      resolution of the anterior wall of the uterus, delineating the myometrial
      thickness in the area of the placental implantation site. With superior image
      quality, the 3D VCI technique facilitates the evaluation of the myometrial
      thickness and the depth of placental invasion due to significantly improved
      enhancement of the contrast and differentiation between various tissues compared
      to the 2D scan. CONCLUSION: We describe for the first time the application of 3D
      VCI and TUI for the visualization of the depth of placental invasion in such a
      case. Preoperative ultrasound diagnosis allows appropriate preoperative
      preparations and the decision to leave the placenta untouched to avoid a probable
      fatal outcome for the patient.

PMID- 21080311
TI  - Ultrasound assessment of tension-free vaginal tape (TVT).
AB  - PURPOSE: To date, no standardization for the visualization of tension-free
      vaginal tape (TVT) has been established in clinical practice. The aim of this
      prospective observational study was to evaluate the shape and position of the
      tape using ultrasound and to compare this data with clinical postoperative
      results. MATERIALS AND METHODS: In a three-year period, 296 patients with
      clinically and urodynamically proven stress urinary incontinence (SUI) were
      treated with TVT and received follow-up in our department. An additional 12
      patients, who were initially treated in other hospitals and had postoperative
      problems, were included in this study. Depending on the outcome after 3 months,
      the patients were divided into groups with and without specific disorders. The
      TVT was evaluated by introital ultrasound. The position of the tape was
      established by its location in relation to the urethral length and the distance
      to the hypoechoic center of the urethra (HCU). RESULTS: A suitable TVT position
      was determined in patients without any postoperative disorders. The mean value
      for the TVT position at rest in relation to the urethral length was 61 %. The
      distance to the HCU was 4.6 +/- 1.5 mm. In patients with persistent SUI, the tape
      was more often located under the inner (3 % vs. 0 %) or outer quarter (29 % vs.
      13 %, p = 0.004). In patients with residual volume, the distance to the urethra
      was significantly lower (2.7 vs. 4.6, p < 0.001). CONCLUSION: TVT may be
      regularly investigated using ultrasound. In combination with the clinical
      outcome, it represents an important method of evaluating the tape and assists in
      the planning of a future therapeutic course of action in cases of postoperative
      problems.

PMID- 21080312
TI  - [The sternoclavicular luxation].
AB  - INTRODUCTION: Injuries of the sternoclavicular joint are rare. Probably these
      injuries are frequently missed. Distorsion type lesions mostly heal uneventfully.
      Their diagnosis and treatment may be demanding. Untreated, a dislocation of the
      sternoclavicular joint and dislocation fractures may lead to considerable
      discomfort or even a risk for neurovascular damage. This work focuses on the
      anatomy and lesions of the sternoclavicular joint, the pathomechanism of the
      injury and the treatment options according to our acute trauma-patient
      collective. METHOD: Five patients with sternoclavicular impairment have been
      assessed. Radiological evaluation consisted in standard chest X-rays. In the
      situation of a fracture and/or complete luxation, CT scans of the
      sternoclavicular joints were additionally performed. Two of our patients
      underwent surgery (one osteosynthesis with a plate and one reduction and ligament
      reconstruction were performed), in one case dislocation was reduced in a closed
      way in a short-lasting general anaesthesia and in two cases conservative
      treatment was performed. RESULTS: In all cases the chosen treatment protocol led
      to symmetrical arm function and all patients were pain-free 2 to 6 months after
      the injury. In one patient the plate was removed 4 months after osteosynthesis.
      CONCLUSION: Distorsions of the sternoclavicular joints are probably
      underdiagnosed and often mildly symptomatic. Conservative treatment usually leads
      to satisfying functional results with significant pain reduction. Non-reducible
      dislocations and dislocation fractures have to be treated operatively. Many
      different open procedures have been described, such as ligament reconstructions
      and osteosynthesis. The postoperative results are generally good, but operative
      treatment may be difficult and at risk for complications. Indications for
      operative treatment of joint subluxation should be strictly limited because of
      the high risk of accompanying neurovascular impairment during manipulation and
      fixation.

PMID- 21080313
TI  - [Balloon kyphoplasty in the treatment of osteoporotic vertebral fractures:
      indications - treatment strategy - complications].
AB  - BACKGROUND: Considering the demographic changes in the populations of Germany and
      Europe as a whole, the field of geriatric traumatology is gaining more and more
      importance within the specialty of orthopedic and trauma surgery. The high
      prevalence of osteoporosis in this specific group of patients poses a special
      challenge, with vertebral compression fractures being the by far most common
      osteoporosis-related fractures. These fractures present with acute as well as
      chronic back pain leading to severe consequences for the affected patients.
      Mobility and quality of life are often heavily impaired. Furthermore, higher
      morbidity and mortality as well as higher risk for further fractures have been
      proven in these patients. METHOD: Balloon kyphoplasty has become a more
      frequently used therapy and is now offered broadly. This treatment addresses
      stable fractures not involving the posterior margin of the vertebrae. With
      increasing application of this surgical procedure the number of complication
      reports is also rising. The following article gives an overview of the technique,
      indications and the possible complications by giving several examples from the
      daily practice and reviewing the relevant literature. RESULTS: Cement leakage of
      the treated vertebrae is the most common complication associated with balloon
      kyphoplasty. In almost all cases this occurs due to too early application of the
      cement, not having reached its optimum in viscosity. Literature research shows a
      percentage rate of about 9% for cement leakage. Thus, balloon kyphoplasty
      provides more safety for the patient than vertebroplasty, for which cement
      leakage rates of up to 41% are reported. Other studies report cement leakage
      ratios of 4-10% for kyphoplasty versus 20-70% for vertebroplasty. Overall the
      percentage of cement leakage is clearly increased in osteoporotic fractures
      compared to non-osteoporotic fractures, with the cement leaking mainly into the
      spinal disc space. So far, valid data in order to further explore the
      consequences of intradiscal cements are lacking. Most relevant for everyday
      practice are cement leakages that have become symptomatic. Depending on the
      localisation they present with dysaesthesia culminating in radicular pain or even
      paraplegia. Cement leakage into vessels can, depending on the amount of cement,
      lead to embolism of pulmonary arteries. Complications due to the surgical
      technique, postoperative infections, bleeding or cardiovascular complications are
      rare with less than 1%. The probability for symptomatic cement leakage averages
      about 1.3% for balloon kyphoplasty. Another discussion, for which at present
      there is no evidence-based verification, is concerned with the higher risk for
      adjacent vertebral fractures after cement augmentation of an osteoporotic
      vertebral compression fracture. At present the degree of osteoporosis and more
      important the number of osteoporosis-related fractures must be the relevant
      predictor for adjacent fractures of neighbouring vertebrae. CONCLUSION: Balloon
      kyphoplasty is a highly standardised and widely used minimally invasive procedure
      for stabilising and augmenting painful osteoporotic fractures of the vertebral
      body. When surgery is indicated carefully and is carried out subtly, the risk of
      complications is reasonable and the outcome is promising. Viscosity of the used
      cement has to be adequate and it must not be inserted with too high a pressure. A
      causal connection between cement viscosity and risk of cement leakage has been
      proven in experimental studies. During application of PMMA cement a thorough
      fluoroscopic monitoring must take place in order to detect cement leakage at an
      early stage and if necessary stop application. These procedures should be
      reserved for clinical centres and surgeons who are able to surgically handle
      possible complications such as compression of the spinal cord. On the basis of
      our own experience we also recommend treatment in a hospital with an integrated
      osteoporosis centre and consecutive treatment in specialised outpatient care.
      Standards in primary care as well as after treatment can be introduced thereby.
      Also communication with practitioner concerned with outpatient care is
      simplified, which leads to enduring therapeutic outcome.

PMID- 21080314
TI  - [Complex ligament instabilities after "open book"-fractures of the pelvic ring -
      finite element computer simulation and crack simulation].
AB  - BACKGROUND: Instability of pelvic ring fractures is also caused by ligament
      disruption. Classifications are based on the major forces leading to fracture.
      Data from injury mechanisms as well as clinical and radiological criteria are
      used to determine the degree of instability. The major aim of all kinds of
      stabilisation is the anatomic reconstruction of the bony pelvic ring. The injured
      ligamentous apparatus is still ignored. Some clinical trials assume that soft
      tissue injuries may be the reason for the poor patient outcome in "open book"
      pelvic ring fractures. The aim of the study was to develop a realistic finite
      element (FE) computer model to simulate "open book" fractures and predict injury
      associated instabilities for osteosynthesis planning. PATIENTS/MATERIAL: We
      developed a realistic FE computer model of the pelvic ring based on CT data. With
      anatomic studies a computer model of the ligamentous apparatus was created and
      inserted into the pelvic ring to complete the bone-ligament complex. Numerical
      simulations were performed to identify the influence of single pelvic ligaments
      on the shifting at the intact anterior and posterior pelvic ring. Additionally, a
      biomechanical validated virtual crack simulation with anterior-posterior
      compression forces was undertaken to predict complex instabilities in "open book"
      pelvic ring fractures. RESULTS: The pelvic ligaments have local and general
      stabilising functions. The sacrospinous and sacrotuberous ligaments are providing
      the vertical load transfer, whereas the ligaments of the iliosacral joint and the
      iliolumbal ligament are necessary for the horizontal load transfer. In "open
      book" fractures ligaments are ruptured stepwise from anterior to posterior. If
      the intraosseous and posterior ligaments of the iliosacral joint are intact, only
      single rotational instability along the ipsilateral iliosacral joint occurs. If
      the ligaments at the posterior pelvic ring are ruptured too, a second axis across
      both iliosacral joints was measured. In this particular case additional
      stabilisation of the posterior pelvic ring should be performed. CONCLUSION: With
      numerical simulations, prediction of injury-associated instabilities is possible.
      Because of incomplete radiological data the implementation of patient-specific FE
      pelvic computer models into the clinical routine is still not realistic.

PMID- 21080316
TI  - The effects of the Health Insurance Portability and Accountability Act privacy
      rule on influenza research using geographical information systems.
AB  - The Health Insurance Portability and Accountability Act (HIPAA) privacy rule was
      enacted to protect patients' personal health information from undue disclosure.
      Despite its intention to protect patients, recent reports suggest that HIPAA
      restrictions may be negatively impacting health research. Quantitative, visual
      geographical and statistical analysis of zip code geographical information
      systems (GIS) mapping, comparing 3-digit HIPAA-compliant and 5-digit HIPAA-non
      compliant simulated data, was chosen to identify and describe the type of
      distortion that may result. It was found that unmitigated HIPAA compliance with
      HIPAA mapping rules distorted the GIS zip code data by 28% leading to erroneous
      results. Thus, compliance with HIPAA privacy rule when mapping may lead
      investigators to publish erroneous GIS maps.

PMID- 21080317
TI  - Mapping and predicting malaria transmission in the People's Republic of China,
      using integrated biology-driven and statistical models.
AB  - The purpose of this study was to deepen our understanding of Plasmodium vivax
      malaria transmission patterns in the People's Republic of China (P.R. China). An
      integrated modeling approach was employed, combining biological and statistical
      models. A Delphi approach was used to determine environmental factors that govern
      malaria transmission. Key factors identified (i.e. temperature, rainfall and
      relative humidity) were utilized for subsequent mapping and modeling purposes.
      Yearly growing degree days, annual rainfall and effective yearly relative
      humidity were extracted from a 15-year time series (1981-1995) of daily
      environmental data readily available for 676 locations in P.R. China. A suite of
      eight multinomial regression models, ranging from the null model to a fully
      saturated one were constructed. Two different information criteria were used for
      model ranking, namely the corrected Akaike's information criterion and the
      Bayesian information criterion. Mapping was based on model output data,
      facilitated by using ArcGIS software. Temperature was found to be the most
      important environmental factor, followed by rainfall and relative humidity in the
      Delphi evaluation. However, relative humidity was found to be more important than
      rainfall and temperature in the ranking list according to the three single
      environmental factor regression models. We conclude that the distribution of the
      mosquito vector is mainly related to relative humidity, which thus determines the
      extent of malaria transmission. However, in regions with relative humidity >60%,
      temperature is the major driver of malaria transmission intensity. By integrating
      biology-driven models with statistical regression models, reliable risk maps
      indicating the distribution of transmission and the intensity can be produced. In
      a next step, we propose to integrate social and health systems factors into our
      modeling approach, which should provide a platform for rigorous surveillance and
      monitoring progress towards P. vivax malaria elimination in P.R. China.

PMID- 21080318
TI  - TerraSAR-X high-resolution radar remote sensing: an operational warning system
      for Rift Valley fever risk.
AB  - In the vicinity of the Barkedji village (in the Ferlo region of Senegal), the
      abundance and aggressiveness of the vector mosquitoes for Rift Valley fever (RVF)
      are strongly linked to rainfall events and associated ponds dynamics. Initially,
      these results were obtained from spectral analysis of high-resolution (~10 m)
      Spot-5 images, but, as a part of the French AdaptFVR project, identification of
      the free water dynamics within ponds was made with the new high-resolution (down
      to 3-meter pixels), Synthetic Aperture Radar satellite (TerraSAR-X) produced by
      Infoterra GmbH, Friedrichshafen/Potsdam, Germany. During summer 2008, within a 30
      x 50 km radar image, it was found that identified free water fell well within the
      footprints of ponds localized by optical data (i.e. Spot-5 images), which
      increased the confidence in this new and complementary remote sensing technique.
      Moreover, by using near real-time rainfall data from the Tropical Rainfall
      Measuring Mission (TRMM), NASA/JAXA joint mission, the filling-up and flushing
      out rates of the ponds can be accurately determined. The latter allows for a
      precise, spatio-temporal mapping of the zones potentially occupied by mosquitoes
      capable of revealing the variability of pond surfaces. The risk for RVF infection
      of gathered bovines and small ruminants (~1 park/km(2)) can thus be assessed.
      This new operational approach (which is independent of weather conditions) is an
      important development in the mapping of risk components (i.e. hazards plus
      vulnerability) related to RVF transmission during the summer monsoon, thus
      contributing to a RVF early warning system.

PMID- 21080320
TI  - Modeling the distribution of Culex tritaeniorhynchus to predict Japanese
      encephalitis distribution in the Republic of Korea.
AB  - Over 35,000 cases of Japanese encephalitis (JE) are reported worldwide each year.
      Culex tritaeniorhynchus is the primary vector of the JE virus, while wading birds
      are natural reservoirs and swine amplifying hosts. As part of a JE risk analysis,
      the ecological niche modeling programme, Maxent, was used to develop a predictive
      model for the distribution of Cx. tritaeniorhynchus in the Republic of Korea,
      using mosquito collection data, temperature, precipitation, elevation, land cover
      and the normalized difference vegetation index (NDVI). The resulting probability
      maps from the model were consistent with the known environmental limitations of
      the mosquito with low probabilities predicted for forest covered mountains. July
      minimum temperature and land cover were the most important variables in the
      model. Elevation, summer NDVI (July-September), precipitation in July, summer
      minimum temperature (May-August) and maximum temperature for fall and winter
      months also contributed to the model. Comparison of the Cx. tritaeniorhynchus
      model to the distribution of JE cases in the Republic of Korea from 2001 to 2009
      showed that cases among a highly vaccinated Korean population were located in
      high-probability areas for Cx. tritaeniorhynchus. No recent JE cases were
      reported from the eastern coastline, where higher probabilities of mosquitoes
      were predicted, but where only small numbers of pigs are raised. The geographical
      distribution of reported JE cases corresponded closely with the predicted high
      probability areas for Cx. tritaeniorhynchus, making the map a useful tool for
      health risk analysis that could be used for planning preventive public health
      measures.

PMID- 21080319
TI  - Planning for Rift Valley fever virus: use of geographical information systems to
      estimate the human health threat of white-tailed deer (Odocoileus virginianus)
      related transmission.
AB  - Rift Valley fever (RVF) virus is a mosquito-borne phlebovirus of the Bunyaviridae
      family that causes frequent outbreaks of severe animal and human disease in sub
      Saharan Africa, Egypt and the Arabian Peninsula. Based on its many known
      competent vectors, its potential for transmission via aerosolization, and its
      progressive spread from East Africa to neighbouring regions, RVF is considered a
      high-priority, emerging health threat for humans, livestock and wildlife in all
      parts of the world. Introduction of West Nile virus to North America has shown
      the potential for "exotic" viral pathogens to become embedded in local ecological
      systems. While RVF is known to infect and amplify within domestic livestock, such
      as taurine cattle, sheep and goats, if RVF virus is accidentally or intentionally
      introduced into North America, an important unknown factor will be the role of
      local wildlife in the maintenance or propagation of virus transmission. We
      examined the potential impact of RVF transmission via white-tailed deer
      (Odocoileus virginianus) in a typical north-eastern United States urban-suburban
      landscape, where livestock are rare but where these potentially susceptible,
      ungulate wildlife are highly abundant. Model results, based on overlap of
      mosquito, human and projected deer densities, indicate that a significant
      proportion (497/1186 km(2), i.e. 42%) of the urban and peri-urban landscape could
      be affected by RVF transmission during the late summer months. Deer population
      losses, either by intervention for herd reduction or by RVF-related mortality,
      would substantially reduce these likely transmission zones to 53.1 km(2), i.e. by
      89%.

PMID- 21080321
TI  - Temperature-derived potential for the establishment of phlebotomine sandflies and
      visceral leishmaniasis in Germany.
AB  - Climate change is expected to manifest in the shift of organisms to regions where
      they were not present in the past, potentially entailing previously unseen
      biological risks. However, studies evaluating these future trends are scarce.
      Here, an important group of vectors (sandflies) and the pathogen transmitted
      (Leishmania infantum complex) causing the infectious disease visceral
      leishmaniasis is investigated, focussing on potential establishment in Germany
      during the 21st century. As the most important habitat factor, temperature
      requirements of pathogen and vector were derived from the literature and compared
      with recent climate records - provided by worldclim - and climate change
      scenarios. Climate data from the Regional Climate Model REMO were obtained and
      averaged over the time periods 2011- 2040, 2041-2070 and 2071-2100. Projected
      temperature changes (based on the A1B and A2 scenarios) were correlated with the
      constraints of vector and pathogen. Simulated potentially suitable habitat areas
      for vector and pathogen were merged to generate a temperature-derived risk map of
      visceral leishmaniasis. Temperature conditions seem to become suitable for the
      vector across large swaths of Germany. Nevertheless, temperature constraints for
      the pathogen may defer the establishment of the parasitic disease, particularly
      during the first half of the 21st century. Long-lasting epidemics of visceral
      leishmaniasis are therefore not expected in Germany during the next few decades,
      although during extremely warm years an increase in autochthonous cases of
      leishmaniasis may occur. The southwest (Upper Rhine Valley) and west (Cologne
      Bight) of Germany are identified as risk areas. The time of potential
      establishment and corresponding rise in biological risk varies between scenarios,
      due to differences in the predicted rate of temperature increase.

PMID- 21080322
TI  - Ecological study and risk mapping of visceral leishmaniasis in an endemic area of
      Iran based on a geographical information systems approach.
AB  - Between 1998 and 2001, a total of 1,062 human cases of visceral leishmaniasis
      were reported from the rural district of Meshkin-Shahr in the mountainous, north
      western Iranian province of Ardabil. In the summer of 2008, a cross-sectional
      study of dogs was conducted in this endemic area by randomly selecting 384
      animals from 21 villages and testing them serologically for leishmaniasis.
      Villages, in which more than 10% of investigated dogs showed anti- Leishmania
      titres >= 1/320, were considered to be high-risk environments. Regression
      analysis showed no statistically significant correlation between topographic
      conditions and the prevalence of positive cases. However, when the results were
      compared with past meteorological records, a statistically significant positive
      correlation (P = 0.007) was found between the number of infected dogs with anti
      Leishmania titres >= 1/640 and the number of days in a year with temperatures
      below 0  degrees C. While humidity showed an inverse correlation (P = 0.009) with
      the anti-Leishmania titres, a positive correlation (P <0.001) was found in
      relation to the amount of rainfall. Mapping of the areas at risk for kala-azar in
      the Meshkin-Shahr district supports the impression that the low temperatures
      prevalent in the Ardebil province constitute an important factor influencing the
      distribution of leishmaniasis there.

PMID- 21080323
TI  - Environmental inducers of schistosomiasis mansoni in Campinas, Brazil.
AB  - Human occupation/activity in the suburbs of the large cities in Brazil, together
      with high social vulnerability associated with poor living conditions, influence
      the dynamics of schistosomiasis mansoni as well as several other emerging and re
      emerging diseases. Previous notification data surveys for Campinas, Sao Paulo
      state, Brazil, carried out by the Information System for Notification Disease,
      show that there are distinct prevalence differences across healthcare districts
      of the city. This paper supports the hypothesis that the distribution of
      schistosomiasis is not random and that the centralized location of cases are
      linked to human behaviour, in particular to human activities that interfere with
      basic landscape structure. This paper analyzes the spatial patterns of the
      parasitic worm Schistosoma mansoni and its intermediate host Biomphalaria
      comparing disease prevalence with natural conditions and the current pattern of
      territory occupation by the population. The spatial and hierarchical distribution
      of factors related to the environmental conditions and land use that indicate the
      risk for schistosomiasis has been surveyed. It was found that landscape
      characteristics define the areas at risk for this endemic disease and, as a
      result, a risk map comprising different risk classes was established. This risk
      map highlights the regions prone to become new foci for infection or that serves
      to maintain an existing focus. The research approach used attempts to introduce
      "geotechnology", i.e. a social application in which better knowledge about these
      foci, designated endemic "hot spots" can assist preventive public intervention
      measures in a way that is inexpensive and easy to handle.

PMID- 21080324
TI  - The relative risk of spatial cluster occurrence and spatiotemporal evolution of
      meningococcal disease in Niger, 2002-2008.
AB  - Meningococcal disease is a major public health concern in Sahelian Africa, where
      over half of the cases reported worldwide occur. In an effort to find annual
      spatial clusters of meningococcal disease and in order to study their evolution
      in Niger from January 2002 to June 2008, a prospective study of routine national
      surveillance data was conducted pertaining to patients with suspected bacterial
      meningitis. The diagnoses were obtained by analysing patients' cerebrospinal
      fluid, using polymerase chain reaction or bacteriology. SatScan using Poisson's
      model was used to calculate the relative risk (RR) of occurrence of spatial
      clusters. In the 2002-2003 period, 15 spatial clusters of meningococcal
      meningitis were detected in a total of 3,979 cases with a maximum number of 558
      cases per cluster in the south-eastern part of the country (70.5% of all cases
      that year; RR = 7.85; P <0.001). Other clusters were found in the following years
      in approximately the same area as those detected in 2002-2003. These clusters
      were identified in the southeast, which allowed us to identify high-risk groups
      in this part of the country. Statistically significant spatio- temporal patterns
      were found, which should be useful in establishing hypotheses for prospective
      studies on epidemic tendencies and empirical risk factors in the African
      meningitis belt.

PMID- 21080325
TI  - Mapping brucellosis risk in communities in the Republic of Armenia.
AB  - We describe the geographical patterns and identified factors associated with
      serological evidence of brucellosis in ruminants in Armenian communities during
      2006 and 2007. The data comprised the two first complete years of the current
      national test-and-slaughter control programme for cattle, sheep and goats.
      Overall, 29% and 21% of the 858 communities involved in this study reported
      brucellosis in their respective cattle and small ruminant populations. The
      national brucellosis control data showed a widespread and uneven distribution of
      brucellosis throughout the Republic of Armenia for both cattle and small
      ruminants. The geographical areas of greater risk of communities having
      seropositive animals were different for cattle and small ruminant populations but
      most of the associated factors were similar. Several areas where the likelihood
      of disease occurrence was predicted poorly by the statistical models were also
      identified. These latter findings are indicative of either less than perfect
      testing and reporting procedures or unexplained epidemiological factors operating
      in those particular areas. The analyses provided valuable insights into
      understanding the brucellosis epidemiology at the community level which operates
      in small ruminant and cattle populations, and identified priority areas for
      implementing targeted risk-based surveillance and disease control interventions.

PMID- 21080326
TI  - Spatio-temporal evaluation of cattle trade in Sweden: description of a grid
      network visualization technique.
AB  - Understanding the intensity and spatial patterns of animal transfers is of prime
      importance as geographical moves play an important part in the spread and
      potential control of contagious animal diseases of veterinary importance. For the
      purpose of visualizing all registered between-herd animal movements in Sweden
      between 1 July 2005 and 31 December 2008 by map animation, a grid network
      technique based on the Bresenham line algorithm was developed. Potential spatio
      temporal clustering of animals registered as sold or purchased based on location
      and month of trade was also detected and tested using a spatial scan statistic.
      Calculations were based on data from 31,375 holdings and 3,487,426 head of
      cattle. In total, 988,167 between-herd movements of individual bovines were
      displayed in a sequence of maps covering three and a half years by 2-week
      intervals. The maps showed that several cattle movements, both short- and long
      distance, take place in Sweden each week of the year. However, most animals (75%)
      were only registered at one single holding during the study period and 23% were
      sold to a different holding once. Spatial scan statistics based on data from the
      year 2008 indicated uneven distributions of purchased or sold animals in space
      and time. During each autumn, there was an increase in cattle movements and
      October and November showed significantly more cases of sold or purchased animals
      (relative risk ~1.7, p = 0.001). Based on the results, we conclude that cattle
      trade is constantly active at a considerable level. This, in combination with
      possibly insufficient biosecurity routines applied on many farms, constitutes a
      risk that contagious diseases are spread in the population. The grid network maps
      were generated through the use of open-source tools and software in order to
      decrease software costs and facilitate sharing of programme code. In addition,
      the technique was based on scripts that allow for the inclusion of iterative
      processes and that comprise all main parts of map creation. Thereby, a large
      number of maps can be generated and the demands for high reproducibility are met.

PMID- 21080327
TI  - The environmental impact of buffalo manure in areas specialized in mozzarella
      production, southern Italy.
AB  - Buffalo livestock plays a central role in the regional economy in some areas of
      southern Italy, through the production of mozzarella cheese. With about 250,000
      heads per utilizable agricultural area (equal to 107,400 ha), livestock husbandry
      is intensive. An important issue with regard to high animal density is manure
      management, an activity determined by cost optimization and the laws governing
      environmental sustainability. According to community, national and international
      rules (European Directive 91/676, Italian rules 152/99 and 258/00), nitrate
      leakage is considered a pollution indicator related to breeding activities and
      must be kept within limits. Simulation studies were carried out in the Italian
      province of Caserta to evaluate the impact of leakage on groundwater. Manure was
      also collected from 35 livestock farms and the nitrogen content measured in the
      laboratory. The results showed an average content of 2 kg/m3 of nitrogen,
      corresponding to 50 kg per animal and year, while the nitrate concentrations in
      the groundwater were found to be lower than those predicted by simulation. The
      nitrogen content found in buffalo manure <60% of the standard content produced by
      the bovine species (on average 83 kg nitrogen per adult animal per year). The
      fact that the bovine species is used as the standard reference for legislation on
      nitrogen production explains the inconsistency observed between the impact of
      buffalo livestock on the environment predicted by simulation and the nitrate
      concentration measured in the groundwater. Although it would be out of line with
      current regulations, it would theoretically be possible to increase the buffalo
      load on the territory without environmentally negative effects. Therefore, in
      this context, the common referral points, i.e. the American Midwest Point Service
      and others usually consulted for the assessment of livestock impact in terms of
      nutritional excretion and the risk of pollution for the environment, should be
      revisited.

PMID- 21080328
TI  - The ecology of domestic violence: the role of alcohol outlet density.
AB  - Studies have consistently found positive associations between the density of
      alcohol outlets and levels of violence in areas. Few studies have examined
      whether this relationship holds for domestic violence. This study assesses
      whether alcohol outlet density is related to domestic violence and whether this
      relationship is due to alcohol availability or to co-occurring economic
      disadvantage and social disorganisation. Cross-sectional data on family
      incidents, liquor outlets and socio-demographic characteristics were obtained for
      217 postcodes in Melbourne, Australia. These data were used to construct models
      assessing the association between alcohol outlet density and domestic violence,
      both with and without controlling for socio-demographic factors. Models were
      tested for spatial autocorrelation, and spatial- error models were developed to
      control for its influence. Outlet density was significantly associated with rates
      of domestic violence, even controlling for socio-demographic factors. The density
      of hotels (pubs) was positively associated with domestic violence rates and the
      density of restaurants and bars was negatively associated with domestic violence.
      Socio-economic disadvantage was also associated with domestic violence rates. The
      density of packaged liquor outlets was not associated with rates of domestic
      violence. The results present a mixed picture, and further study is required to
      develop a clearer understanding of the links between alcohol availability and
      domestic violence.

PMID- 21080333
TI  - Reconstitution of human MCF-7 breast cancer cells with caspase-3 does not
      sensitize them to action of CDK inhibitors.
AB  - Human MCF-7 breast cancer cells are resistant to pro-apoptotic stimuli due to
      caspase-3 inactivation. On the other hand, they should be sensitive to agents
      like selective pharmacological inhibitors of cyclin-dependent kinases (CDKs) that
      (re)activate p53 tumor suppressor protein because they harbor intact p53
      pathways. In this study we examined whether reconstitution of caspase-3 in MCF-7
      cells sensitizes them to inhibitors of CDKs, by analyzing the effects of
      roscovitine (ROSC) and olomoucine (OLO), two closely related selective
      pharmacological CDK inhibitors, on both mother MCF-7 cells and a secondary mutant
      line, MCF-7.3.28 that stably expresses human caspase-3. The results show that
      ROSC is, as expected, much more potent than OLO. Surprisingly; however, ROSC and
      OLO reduced proliferation of parental MCF-7 cells more strongly than caspase-3
      proficient counterparts. Both inhibitors arrest human breast cancer cells at the
      G(2)-phase of the cell cycle. Analysis of cell-cycle regulators by immunoblotting
      revealed that ROSC strongly induces p53 protein activity by inducing its
      phosphorylation at Ser46 in the MCF-7 cells lacking caspase-3, but not in caspase
      3-proficient cells. Furthermore, reconstitution of caspase-3 in MCF-7 cells
      neither elevates the mitochondrial apoptosis rate nor significantly increases
      caspases activity upon ROSC treatment. However, the stabilization of p53 in
      response to DNA damaging agents is the same in both caspase negative and positive
      MCF-7 cells. Cytotoxic agents induce caspase-3-dependent apoptosis in caspase-3
      proficient cells. These results indicate that reconstitution of MCF-7 cancer
      cells with caspase-3 sensitize them to the action of DNA damaging agents but not
      to ATP-like pharmacological inhibitors of CDKs.

PMID- 21080337
TI  - Regulation of Dab2 expression in intestinal and renal epithelia by development.
AB  - Disabled-2 (Dab2) is an intracellular adaptor protein proposed to function in
      endocytosis. Here, we investigate the intestinal and renal Dab2 expression versus
      maturation. Dab2 mRNA levels measured by RT-PCR are greater in the small than in
      the large intestine. Immunological studies localize Dab2 to the terminal web
      domain of the enterocytes and reveal the presence of a 96-kDa Dab2 isoform in the
      apical membrane of the jejunum, ileum, and renal cortex of the suckling and adult
      rat. A 69-kDa Dab2 isoform is only observed in the apical membranes of the
      suckling ileum. During the suckling period, the Dab2 mRNA levels measured in the
      enterocytes and crypts and those of the 96-kDa Dab2 isoform are greater in the
      ileum than in the jejunum. No segmental differences are observed in the adult
      intestine. In the intestine, the levels of Dab2 mRNA and those of the 96-kDa Dab2
      isoform decrease to adult values at weaning, whereas in the kidney they increase
      with development. Weaning the pups on a commercial milk diet slows the
      periweaning decline in the levels of Dab2 mRNA in the crypts and of those of the
      96-kDa isoform. This is the first report showing that the 96-kDa Dab2 isoform is
      expressed at the apical domain of rat small intestine, that ontogeny regulates
      Dab2 gene expression in intestine and kidney and that retarding weaning affects
      intestinal Dab2 gene expression.

PMID- 21080338
TI  - Ginsenoside Rh2 induces Bcl-2 family proteins-mediated apoptosis in vitro and in
      xenografts in vivo models.
AB  - The cancer chemoprevention effects of ginseng saponins have been demonstrated
      against a variety of experimental tumors; however, their molecular mechanisms in
      vitro and in in vivo models are not well studied. This study was undertaken to
      gain insights into the molecular mechanisms of ginsenoside Rh2 (Rh2)-induced cell
      death in human breast cancer cell lines as well as in in vivo xenografts. Rh2
      treatment significantly inhibited viability of both MCF-7 and MDA-MB-231 human
      breast cells in a concentration-dependent manner, which correlated with
      mitochondria-mediated apoptosis. Rh2-induced apoptosis was accompanied by the
      down-regulation of antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1. It also
      caused induction of the proapoptotic members Bak, Bax, and Bim leading to
      mitochondrial translocation of Bax and activation of caspases. Moreover, Rh2
      induced apoptosis was partially, yet significantly protected by transient
      transfection of MCF-7 cells with Bax- and Bak-targeted siRNAs. Oral gavage of 5
      mg Rh2/kg of mouse (three times a week) significantly caused apoptosis of MDA-MB
      231 xenografts. An increase in Bax and Bak and a decrease in Bcl-2 and Bcl-xL
      transcript levels, in accordance with their protein expression, were observed in
      tumor tissue. Tumors from Rh2-treated mice exhibited a markedly higher count of
      apoptotic bodies and reduced proliferation index compared with control tumors.
      Our data suggest that Rh2 used in traditional oriental medicine for the treatment
      of various ailments, may be an attractive agent for the treatment and/or
      prevention of human breast cancers.

PMID- 21080339
TI  - Hepcidin in anemia of chronic heart failure.
AB  - Anemia is a common finding among patients with chronic heart failure (HF).
      Although comorbidities, such as kidney failure, might contribute to the
      pathogenesis of anemia, many patients with HF do not have any other obvious
      etiology for their anemia. We investigated whether anemia in HF is associated
      with an elevation in hepcidin concentration. We used time-of-flight mass
      spectrometry to measure hepcidin concentration in urine and serum samples of
      patients with HF and in control subjects. We found that the concentration of
      hepcidin was lower in urine samples of patients with HF compared with those of
      control subjects. Serum hepcidin was also reduced in HF but was not significantly
      lower than that in controls. There were no significant differences between
      hepcidin levels in patients with HF and anemia compared with patients with HF and
      normal hemoglobin level. We concluded that hepcidin probably does not play a
      major role in pathogenesis of anemia in patients with chronic HF.

PMID- 21080340
TI  - Demonstration of additional benefit in adding lenalidomide to azacitidine in
      patients with higher-risk myelodysplastic syndromes.
AB  - Lenalidomide and azacitidine are active in MDS patients, and may complement each
      other by targeting the bone marrow microenvironment and the malignant clone. A
      recent Phase I trial testing the lenalidomide and azacitidine combination yielded
      encouraging results; however, lenalidomide's contribution was unclear. In this
      study, 18 higher-risk MDS patients were treated with the combination for seven
      cycles, after which lenalidomide was discontinued in eight patients who achieved
      a complete response, with azacitidine monotherapy continuing until disease
      progression. We report on three patients who relapsed on monotherapy with excess
      blasts at 12, 19, and 24 months, in whom lenalidomide was then resumed in
      combination with azacitidine. Each patient, one with normal cytogenetics at
      relapse; one with a 18 abnormality; and one with del(4q25), recaptured a complete
      response that was sustained for 5, 7, and 7+ months. We conclude that the
      addition of lenalidomide to azacitidine provides additional clinical benefit over
      azacitidine monotherapy.

PMID- 21080342
TI  - C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma
      kinase positive anaplastic large cell lymphoma: Identification of a novel fusion
      gene ALO17/C-MYC.
AB  - Anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma (ALCL)
      is usually associated with a favorable prognosis. We describe an 11-year-old girl
      patient with ALK positive ALCL bearing t(2;5)(p23;q35) and t(8;17)(q24;q25)
      translocations who had an aggressive clinical course despite various combinations
      of intensive chemotherapy. Southern blot analysis identified C-MYC rearrangement.
      Immunohistochemistry and Northern and Western blot analyses revealed cmyc
      overexpression. A new fusion between ALO17 (ALK lymphoma oligomerization partner
      on chromosome 17) and C-MYC was identified by the 50-rapid amplification of cDNA
      ends. This new fusion may have possibly provoked the poor prognosis in this
      patient with ALK positive ALCL, and C-MYC rearrangement may indicate poor
      prognosis in ALCL.

PMID- 21080341
TI  - A reappraisal of Gaucher disease-diagnosis and disease management algorithms.
AB  - Type 1 (non-neuronopathic) Gaucher disease was the first lysosomal storage
      disorder for which an effective enzyme replacement therapy was developed and it
      has become a prototype for treatments for related orphan diseases. There are
      currently four treatment options available to patients with Gaucher disease,
      nevertheless, almost 25% of Type 1 Gaucher patients do not gain timely access to
      therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of
      Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease
      and nonspecific and heterogeneous nature of Gaucher disease symptoms may impede
      consideration of this disease in the differential diagnosis. To help promote
      timely diagnosis and optimal management of the protean presentations of Gaucher
      disease, a consensus meeting was convened to develop algorithms for diagnosis and
      disease management for Gaucher disease.

PMID- 21080343
TI  - Urotensin II receptor predicts the clinical outcome of prostate cancer patients
      and is involved in the regulation of motility of prostate adenocarcinoma cells.
AB  - Urotensin II (UT-II) is a potent vasoconstrictor peptide and its receptor (UTR)
      was correlated with human cortico-adrenal carcinoma proliferation. In this study,
      we have evaluated the correlation between UTR expression and prognosis of human
      prostate adenocarcinoma and the involvement of this receptor in the regulation of
      biological properties on both in vivo and in vitro models. UTR mRNA and protein,
      evaluated by real-time PCR and Western blotting, respectively, were expressed at
      high levels only in androgen-dependent LNCaP cells. In order to investigate UTR
      changes occurring in human prostate tumorigenesis, we have also evaluated the
      expression of UTR in vivo in 195 human prostate tissue samples. UTR was always
      expressed at low intensity in hyperplastic tissues and at high intensity in well
      differentiated carcinomas (Gleason 2-3). Moreover, we have evaluated the effects
      of an antagonist of UTR, urantide on migration and invasion of LNCaP cells.
      Urantide induced a dose-dependent decrease of motility and invasion of LNCaP
      cells whose characteristic ameboid movement seems to be advantageous for their
      malignancy. These effects were paralleled by down-regulating the
      autophosphorylation of focal adhesion kinase and the integrin surface expression
      on LNCaP cells. The effects on cell motility and invasion were likely due to the
      inhibition of RhoA activity induced by both urantide and shRNA UTR. These data
      suggest that UTR can be considered a prognostic marker in human prostate
      adenocarcinoma patients.

PMID- 21080347
TI  - Economic evaluation of multidisciplinary rehabilitation after primary total knee
      arthroplasty based on a randomized controlled trial.
AB  - OBJECTIVE: To conduct an economic evaluation of a multidisciplinary,
      biopsychosocial outpatient rehabilitation program implemented 2-4 months after
      total knee arthroplasty (TKA), compared with conventional orthopedic care.
      METHODS: After surgery, 86 patients were randomized to a multidisciplinary
      rehabilitation group (n = 44) or a conventional orthopedic care group (n = 42).
      Alongside the randomized controlled trial, we estimated the costs of
      rehabilitation, health care resource use, and community support. Information
      about resource use was collected by means of a questionnaire together with data
      from hospital records. The primary outcome (effectiveness) measure was change in
      self-reported functional capacity and the secondary measure was quality-adjusted
      life years (QALYs) gained during the 12-month followup. Cost-effectiveness was
      assessed from between-group differences in costs, change in functional capacity,
      and QALYs gained. RESULTS: Both protocols of providing rehabilitation services
      turned out to be equally effective, but the conventional orthopedic care protocol
      was unequivocally cost saving: the saving was ?1,830 per patient (95% confidence
      interval -548, 3,623) using the available direct cost data. CONCLUSION:
      Multidisciplinary rehabilitation for unselected osteoarthritis patients in the
      subacute period of recovery after TKA is not a cost-effective use of health care
      resources. Similar rehabilitation protocols cannot be recommended for clinical
      pathways of TKA in the future.

PMID- 21080348
TI  - Identification of biomarkers that predict response to treatment of lupus
      nephritis with mycophenolate mofetil or pulse cyclophosphamide.
AB  - OBJECTIVE: There is a need to identify clinical characteristics and/or biomarkers
      that can predict treatment outcome in lupus nephritis. To this end, we utilized
      data from the Aspreva Lupus Management Study to identify possible baseline and
      early predictors of renal response to mycophenolate mofetil (MMF) or intravenous
      (IV) cyclophosphamide (CYC). METHODS: Patients with class III-V lupus nephritis
      were randomized to MMF or IV CYC. We assessed predictors of renal response,
      including baseline demographic, clinical, laboratory, and histologic
      characteristics, as well as early clinical and laboratory data, obtained within
      the first 2 months of therapy. Odds ratios (ORs) and 95% confidence intervals for
      renal response were calculated for each putative predictor. RESULTS:
      Normalization of C3, C4, or both by week 8 was strongly predictive of renal
      response at week 24 (ORs 2.5, 2.6, and 2.9, respectively; P < 0.05). Reduction in
      proteinuria by >=25% by week 8 was predictive of renal response at week 24 (OR
      3.2, P < 0.05). Reduction in anti-double-stranded DNA (anti-dsDNA) by week 8 was
      not predictive of renal response. Only 3 baseline characteristics (C4 level, time
      since diagnosis of lupus nephritis, and estimated glomerular filtration rate
      [GFR]) were predictive of renal response; the remaining characteristics (age, age
      at lupus nephritis onset, time since diagnosis of systemic lupus erythematosus,
      sex, histopathologic class, anti-dsDNA antibody level, C3 level, level of
      proteinuria, and use of angiotensin-converting enzyme inhibitors, statins, or
      hydroxychloroquine) were not. CONCLUSION: This study demonstrates that baseline
      C4 level, time since diagnosis of lupus nephritis, baseline estimated GFR, early
      normalization of complement, and reduction in proteinuria independently predict
      renal response to therapy at 6 months.

PMID- 21080349
TI  - Impact of hallux valgus severity on general and foot-specific health-related
      quality of life.
AB  - OBJECTIVE: To explore the prevalence of and factors associated with hallux valgus
      and to assess the impact of hallux valgus severity on general and foot-specific
      health-related quality of life (HRQOL) in older people. METHODS: People age >=56
      years who participated in the 6-year followup of the North Staffordshire
      Osteoarthritis Project (n = 2,831) completed a survey that included the Medical
      Outcomes Study Short Form 36 (SF-36) health survey and the Manchester Foot Pain
      and Disability Index (FPDI). Self-reported hallux valgus severity was assessed
      using a validated instrument. Comparisons of SF-36 and FPDI scores were made
      across 5 severity grades of hallux valgus. RESULTS: Hallux valgus was present in
      36.3% of the study population and was associated with female sex, older age, and
      pain in other bodily regions. There was a progressive reduction in all SF-36
      component scores as the severity of hallux valgus increased; this association
      remained after adjusting for age, sex, education, and body mass index. The
      strength of these associations diminished after also adjusting for pain in the
      back, hip, knee, and foot, but hallux valgus severity remained significantly
      associated with reduced physical function, bodily pain, general health, social
      function, and mental health subscale scores. Among participants with foot pain,
      increasing hallux valgus severity was also significantly associated with greater
      impairment on the pain and function subscales of the FPDI after adjusting for
      age, sex, and body mass index. CONCLUSION: There is a progressive reduction in
      both general and foot-specific HRQOL with increasing severity of hallux valgus
      deformity.

PMID- 21080350
TI  - Abnormal bone geometry at the metacarpal bone shaft of rheumatoid arthritis
      patients with maintained muscle-bone relationship.
AB  - OBJECTIVE: Metacarpal juxtaarticular bone is altered in rheumatoid arthritis
      (RA). However, a detailed analysis of disease-related geometric adaptations of
      the metacarpal shaft is missing. The aim of the present study was to assess the
      role of RA disease, forearm muscle cross-sectional area (CSA), age, and sex on
      bone geometry at the metacarpal shaft. METHODS: In 64 RA patients and 128 control
      subjects, geometric properties of the third metacarpal bone midshaft and forearm
      muscle CSA were measured by peripheral quantitative computed tomography (QCT).
      Linear models were performed for cortical CSA, total bone CSA, polar stress
      strain index (SSI; a surrogate for a bone's resistance to bending and torsion),
      cortical thickness, and the metacarpal index (MI; cortical CSA/total CSA), with
      the explanatory variables muscle CSA, age, RA status, and sex. RESULTS: Forearm
      muscle CSA was associated with cortical and total metacarpal CSA and polar SSI.
      RA group status was associated with all bone parameters except cortical CSA.
      There was a significant interaction between RA status and age, indicating that
      the RA group had a greater age-related decrease in cortical CSA, cortical
      thickness, and the MI. CONCLUSION: Bone geometry of the metacarpal shaft is
      altered in RA patients compared to healthy controls. Whereas bone mass of the
      metacarpal shaft is adapted to forearm muscle mass, cortical thickness and the MI
      are reduced, but outer bone shaft circumference and the polar SSI increased in RA
      patients. These adaptations correspond to an enhanced aging pattern in RA
      patients.

PMID- 21080353
TI  - Comparative study of the detection of joint injury in early-stage rheumatoid
      arthritis by magnetic resonance imaging of the wrist and finger joints and
      physical examination.
AB  - OBJECTIVE: To verify whether magnetic resonance imaging (MRI)-proven joint injury
      is sensitive as compared with joint injury determined by physical examination.
      METHODS: MRI of the wrist and finger joints of both hands was examined in 51
      early-stage rheumatoid arthritis (RA) patients by both plain and gadolinium
      diethylenetriaminepentaacetic acid-enhanced MRI. Synovitis, bone edema, and bone
      erosion (the latter two included as bone lesions at the wrist joints);
      metacarpophalangeal joints; and proximal interphalangeal joints were considered
      as MRI-proven joint injury. Japan College of Rheumatology-certified
      rheumatologists had given a physical examination just before the MRI study. The
      presence of tender and/or swollen joints in the same fields as MRI was considered
      as joint injury on physical examination. The association of MRI-proven joint
      injury with physical examination-proven joint injury was examined. RESULTS: A
      total of 1,110 sites were available to be examined. MRI-proven joint injury was
      found in 521 sites, whereas the other 589 sites were normal. Physical examination
      proven joint injury was found in 305 sites, which was significantly low as
      compared with MRI-proven joint injury (P = 1.1 * 10(-12) versus MRI). Joint
      injury on physical examination was not found in 81.5% of the sites where MRI
      findings were normal. Furthermore, an association of the severity of MRI-proven
      joint injury with that of joint injury on physical examination was clearly
      demonstrated (P = 1.6 * 10(-15), r(s) = 0.469). CONCLUSION: Our present data
      suggest that MRI is not only sensitive but accurately reflects the joint injury
      in patients with early-stage RA.

PMID- 21080370
TI  - Promoted negative staining of proteins in SDS-PAGE using Eosin B compounded with
      magnesium chloride.
AB  - In this study, we describe an effective visualizing technique for proteins in SDS
      PAGE based on the organic dye, Eosin B, the sensitivity of which can be further
      strengthened by the addition of magnesium to the staining solution after
      electrophoresis. The newly developed protocol is low in cost and easily performed
      compared with the common methods for protein analysis in 1-D and 2-D gels. It
      provides a much better sensitivity (0.2 ng of single protein band) than that of
      imidazole-zinc negative stain for fixing and staining within 1 h, and an
      excellent performance in terms of compatibility with MALDI-TOF MS. The results
      show that similar identification scores and numbers of matched peptides were
      obtained by both methods. Furthermore, the effects of different metal salts on
      the quality of protein visualization by Eosin B were also investigated. Because
      of its sensitivity, stability, and safety, this stain may be a more practical
      method for protein determination in the routine laboratory.

PMID- 21080371
TI  - Application of carbon nanotubes for in-capillary incubations with cytochrome P450
      enzymes.
AB  - The utility of multi-walled carbon nanotubes (MWNTs) to decrease the interaction
      between cytochrome P450 enzymes and the capillary wall during in-capillary
      enzymatic incubation was investigated. First, 18 surfactants were screened to
      determine their MWNT-dispersing capacity. A probe sonication procedure was
      developed in order to attain homogeneous MWNT dispersions within a reasonable
      time. Next, the influence of surfactants and MWNTs on P450 activity was studied,
      employing verapamil and CYP3A4 as model substrate and P450 isoform, respectively.
      MWNTs dispersed in Brij 35 did not affect CYP3A4 activity significantly and were
      selected for subsequent in-capillary tests. An in-line CE assay, involving
      electrophoretic mixing of reagents and zero potential amplification in the
      thermostatted part of the capillary, was developed. In-capillary incubations
      without MWNTs caused adsorption of enzyme to the capillary wall and a concomitant
      decline of capillary lifetime, even when extensive between-run rinsing was
      applied. Addition of MWNTs to the enzyme solution entailed substantial
      improvement of migration time and peak shape repeatability. The performance of
      three types of MWNTs was compared.

PMID- 21080372
TI  - Establishment of an ectopically expressed and functional PRMT1 for proteomic
      analysis of arginine-methylated proteins.
AB  - Protein arginine methylation, catalyzed by protein arginine methyltransferases
      (PRMTs), plays crucial roles in a variety of cellular processes. Mammalian PRMT1
      exists in a large protein complex in cells, which has been implied in modulating
      the regulatory and catalytic properties of this enzyme. Establishment of a
      mammalian comparative approach will help to identify putative substrates of PRMT1
      in an authentic condition. Here, we showed that ectopically expressed PRMT1 in
      mammalian HEK293 cells not only exhibited catalytic properties comparable to the
      endogenous enzyme but also existed in a functional complex together with
      endogenous PRMT1 and thus functioned as an endogenous counterpart. In addition,
      the measured methylation level of cellular proteins using a tritium-labeled
      methyl donor was accordingly enhanced upon ectopic expression of PRMT1.
      Subsequent proteomic analysis with such PRMT1-expressing cells allowed us to
      identify several known and putative methylated proteins. In vitro methylation of
      selected proteins, eukaryotic translation initiation factor 4A-I and vimentin, by
      cellular PRMT1 was shown. Together, we have demonstrated the functional
      equivalence of ectopically expressed PRMT1 in HEK293 cells and its application to
      systematically identify the substrate proteins in a mammalian cell context.

PMID- 21080373
TI  - Evaluation of the polymorphic D-loop of Columba livia in forensic applications.
AB  - We report on the polymorphisms exhibited by three hypervariable regions within
      the D-loop of Columba livia (pigeon) mitochondrial DNA. A total of 131 samples
      were taken from 131 randomly selected birds and used in the analyses of SNPs, a
      variable number of tandem repeats (VNTR) and an STR locus using CE. The number of
      repeats for the VNTR ranged from 2 to 8 producing 21 haplotypes, with 54
      individuals exhibiting heteroplasmy. The STR locus exhibited multiple and
      continuous repeats within each individual and these patterns were not
      reproducible with individuals of the same maternal lineage, where different
      haplotypes were noted. Combining the SNP and VNTR loci produced 38 haplotypes,
      with the power of discrimination being 0.93. The polymorphic regions of D-loop
      observed in this study are potential markers for maternal relationship
      identification.

PMID- 21080375
TI  - T cells acquire cell surface determinants of APC via in vivo trogocytosis during
      viral infections.
AB  - Trogocytosis describes the transfer of surface determinants between immune cells
      and has been implicated in immune regulation. Most findings are based on in vitro
      studies since in vivo trogocytosis of immune cells is difficult to detect under
      physiological conditions. We used low frequencies of memory P14 T cells to
      demonstrate that T cells perform trogocytosis in vivo if in contact with APC
      pulsed with GP33-peptide or expressing the antigen endogenously. Furthermore, in
      vivo trogocytosis of T cells is demonstrated during infections with lymphocytic
      choriomeningitis virus and vaccinia virus. Trogocytosis-positive T cells revealed
      higher expression of activation marker and cytokines, showing a more activated
      phenotype compared to trogocytosis-negative T cells.

PMID- 21080376
TI  - The IgH 3' regulatory region and its implication in lymphomagenesis.
AB  - The 3' regulatory region (3'RR) located downstream of the IgH gene is the master
      element that controls class switch recombination and sustains high-level
      transcription at the plasma-cell stage. This latter role suggests that the 3'RR
      may be involved in oncogene deregulation during the frequent IgH translocation
      events associated with B-cell malignancies. A convincing demonstration of the
      essential contribution of 3'RR in lymphomagenesis has been provided by transgenic
      animal models. The mouse 3'RR shares a strong structural homology with the
      regulatory regions located downstream of each human Calpha gene. Mouse models
      exploring the role of the 3'RR in B-cell physiology and in malignancies should
      provide useful indications about the pathophysiology of human cell lymphocyte
      proliferation.

PMID- 21080378
TI  - Air/Liquid-pressure and heartbeat-driven flexible fiber nanogenerators as a
      micro/nano-power source or diagnostic sensor.
AB  - We present a new approach for fabricating flexible fiber nanogenerators (FNGs)
      that can be used for smart shirts, flexible electronics, and medical
      applications. These FNGs are based on carbon fibers that are covered
      cylindrically by textured zinc oxide (ZnO) thin films. Once subjected to uni
      compression by applying a pressure, the cylindrical ZnO thin film is under a
      compressive strain, resulting in a macroscopic piezopotential across its inner
      and exterior surfaces owing to the textured structure of the film, which is the
      driving force for generating an electric current in the external load. Using such
      a structure, an output peak voltage of 3.2 V and average current density of 0.15
      MUA cm(-2) are demonstrated. The FNGs rely on air pressure, so that it can work
      in a non-contact mode in cases of rotating tires, flowing air/liquid, and even in
      blood vessels. Pressure-driven FNGs added to a syringe show potential to harvest
      energy in blood vessels, gas pipes, and oil pipes, as long as there is a
      fluctuation in pressure (or turbulence). Heart-pulse driven FNGs can serve as
      ultrasensitive sensors for monitoring the behavior of the human heart, which may
      possibly be applied to medical diagnostics as sensors and measurement tools.

PMID- 21080380
TI  - The selfish brain: Competition for energy resources.
AB  - Obesity and type 2 diabetes have become the major health problems in many
      industrialized countries. Here, I present the unconventional concept that a
      healthy organism maintains its systemic homeostasis by a "competent brain-pull",
      i.e., the brain's ability to properly demand glucose from the body, and that the
      underlying cause of obesity is "incompetent brain-pull." I describe the energy
      fluxes from the environment, through the body, toward the brain as the final
      consumer in a "supply chain" model. There is data-based support for the
      hypothesis, which states that under conditions of food abundance incompetent
      brain-pull will lead to build ups in the supply chain culminating in obesity and
      type 2 diabetes. There is also support for the related hypothesis, which states
      that under conditions of food deprivation, a competent brain-pull mechanism is
      indispensable for the continuation of the brain's high energy level. To
      experimentally determine how the competent brain-pull functions to demand for
      cerebral energy, healthy young men undergoing psychosocial stress were studied.
      It was found that the brain under stressful conditions demands for energy from
      the body by using a brain-pull mechanism, which is referred to as "cerebral
      insulin suppression" and in so doing it can satisfy its excessive needs during
      stress. This article gives an overview about the recent work on the "Selfish
      Brain" theory dealing with the maintenance of the cerebral and peripheral energy
      homeostasis.

PMID- 21080381
TI  - An updated analysis of pubertal linear growth characteristics and age at menarche
      in ethnic Chinese.
AB  - OBJECTIVES: Concerns regarding change in the onset and tempo of pubertal growth
      in ethnic Chinese have posed a need for current information on growth
      characteristics. This study is to update the normative data of pubertal linear
      growth characteristics and distribution of age at menarche in healthy Chinese
      adolescents. METHODS: A multistage stratified cluster sampling investigation
      based on age and sex was designed for anthropometric data collection in 2008,
      including 15,204 healthy boys and 13,047 healthy girls. The PB1 mathematical
      growth model was utilized to derive biological parameters of the adolescent
      growth curves. Ages at menarche were estimated in 6,476 girls through probit
      analysis at the ages at which 10%, 25%, 50%, 75%, and 90% of the girls attained
      menarche. RESULTS: The peak growth age (PGA) was 12.6 years for boys and 10.6
      years for girls. The PHV was 6.91 cm/yr in boys and 6.69 cm/yr in girls. The
      overall increments of adult height since 1985 were 3.3 cm for males and 2.3 cm
      for females, yielded rates of 1.4 and 1.0 cm/decade, respectively. Less than 10%
      of Chinese girls experience onset of menses before 11.38 years, and approximately
      90% of all Chinese girls are menstruating by 13.88 years, with a median age of
      12.63 years. CONCLUSIONS: The current study showed an advancing trend in PGA in
      both Chinese boys and girls. Decreasing menarche age was also observed for
      Chinese girls. These updated data would serve as useful reference for
      interpretation of endocrine and growth status and growth disorders in Chinese
      during peripubertal period.

PMID- 21080382
TI  - Dipeptide and tripeptide conjugates as low-molecular-weight hydrogelators.
AB  - Dipeptide and tripeptide conjugates are receiving significant current interest as
      LMWG, driven by the accessibility of these materials, their relatively low cost
      and also the large number of examples that successfully form hydrogels. Their
      behaviour can easily modified by changes in the amino acids or the aromatic end
      groups chosen. The assembly process has been relatively well described for a
      small subset of these gelators, giving a good idea of the behaviour of these
      molecules and allowing an understanding of the conditions under which assembly
      will occur. Here, we critically review the literature in this area and consider
      the importance of gelator choice and method of assembly on the outcome of the
      gelation. We also discuss the applications of these hydrogels.

PMID- 21080383
TI  - Coating of titanium implant materials with thin polymeric films for binding the
      signaling protein BMP2.
AB  - A fast and simple approach for immobilization using copolymers as interlayers is
      reported. The synthesized copolymers form stable self-assembled layers on implant
      materials like, e.g., titanium in a simple coating/drying/washing sequence and
      have functional groups which can bind proteins from an aqueous solution. The
      copolymer films have been characterized via ellipsometry and contact angle
      measurements and were tested for biocompatibility. An immunoassay was used to
      determine the amount of BMP2 and demonstrated an approximately 10-fold increase
      as compared to previously used self-assembled monolayers. A BMP2-responsive cell
      line with luciferase detection was used to determine the biological activity of
      the bound signaling protein.

PMID- 21080384
TI  - Di- and triblock siRNA-PEG copolymers: PEG density effect of polyelectrolyte
      complexes on cellular uptake and gene silencing efficiency.
AB  - Di- and triblock siRNA/PEG copolymers were synthesized and complexed with
      cationic SLN for assessing their gene silencing efficiency as a function of PEG
      density. A sssiRNA and a sassiRNA were separately conjugated with PEG via a
      disulfide linkage. AB-type diblock and ABA-type triblock copolymers were
      successfully prepared by stoichiometric hybridization of sssiRNA-PEG conjugate
      with sassiRNA and sassiRNA-PEG conjugate, respectively. The resultant di- and
      triblock copolymers were characterized by means of GPC and gel electrophoresis.
      The serum stability of siRNA in the copolymers was enhanced as compared to that
      of naked siRNA. Using cationic SLN as a model carrier, the PEGylation density
      effect of the siRNA-PEG/SLN complexes on gene silencing and cellular uptake was
      analyzed.

PMID- 21080386
TI  - Visualizing resonance energy transfer in supramolecular surface patterns of beta
      CD-functionalized quantum dot hosts and organic dye guests by fluorescence
      lifetime imaging.
AB  - Detection of an analyte via supramolecular host-guest binding and quantum dot
      (QD)-based fluorescence resonance energy transfer (FRET) signal transduction
      mechanism is demonstrated. Surface patterns consisting of CdSe/ZnS QDs
      functionalized at their periphery with beta-cyclodextrin (beta-CD) were obtained
      by immobilization of the QDs from solution onto glass substrates patterned with
      adamantyl-terminated poly(propylene imine) dendrimeric "glue." Subsequent
      formation of host-guest complexes between vacant beta-CD on the QD surface and an
      adamantyl-functionalized lissamine rhodamine resulting in FRET was confirmed by
      fluorescence microscopy, spectroscopy, and fluorescence lifetime imaging
      microscopy (FLIM).

PMID- 21080387
TI  - Molecular modulation of conductivity on H-terminated silicon-on-insulator
      substrates.
AB  - The adsorption of a range of molecular species (water, pyridine, and ammonia) is
      found to reversibly modulate the conductivity of hydrogen-terminated silicon-on
      insulator (H-SOI) substrates. Simultaneous sheet-resistance and Hall-effect
      measurements on moderately doped (10(15) cm(-3)) n- and p-type H-SOI samples
      mounted in a vacuum system are used to monitor the effect of gas exposure in the
      Torr range on the electrical-transport properties of these substrates. Reversible
      physisorption of "hole-trapping" species, such as pyridine (C(5)H(5)N) and
      ammonia (NH(3)) produces highly conductive minority-carrier channels (inversion)
      on p-type substrates, mimicking the action of a metallic gate in a field-effect
      transistor. The adsorption of these same molecules on n-type SOI induces strong
      electron-accumulation layers. Minority/majority channels are also formed upon
      controlled exposure to water vapor. These observations can be explained by a
      classical band-bending model, which considers the adsorbates as the source of a
      uniform surface charge ranging from +10(11) to +10(12)q cm(-2). These results
      demonstrate the utility of DC transport measurements of SOI platforms for studies
      of molecular adsorption and charge-transfer effects at semiconductor surfaces.

PMID- 21080388
TI  - A biomembrane stencil for crystal growth and soft lithography of a thermochromic
      molecular sensor.

PMID- 21080392
TI  - Liquid-crystal templating in ammonia: a facile route to micro- and mesoporous
      metal nitride/carbon composites.

PMID- 21080393
TI  - Catalytic enantioselective claisen rearrangements of O-allyl beta-ketoesters.

PMID- 21080394
TI  - P=P, a laboratory reagent?

PMID- 21080395
TI  - Characterization of irreversible kinase inhibitors by directly detecting covalent
      bond formation: a tool for dissecting kinase drug resistance.
AB  - Targeting protein kinases in cancer therapy with irreversible small-molecule
      inhibitors is moving to the forefront of kinase-inhibitor research and is thought
      to be an effective means of overcoming mutation-associated drug resistance in
      epidermal growth factor receptor kinase (EGFR). We generated a detection
      technique that allows direct measurements of covalent bond formation without
      relying on kinase activity, thereby allowing the straightforward investigation of
      the influence of steric clashes on covalent inhibitors in different resistant
      kinase mutants. The obtained results are discussed together with structural
      biology and biochemical studies of catalytic activity in both wild-type and
      gatekeeper mutated kinase variants to draw conclusions about the impact of steric
      hindrance and increased catalytic activity in drug-resistant kinase variants.

PMID- 21080396
TI  - Towards practical Baeyer-Villiger-monooxygenases: design of cyclohexanone
      monooxygenase mutants with enhanced oxidative stability.
AB  - Baeyer-Villiger monooxygenases (BVMOs) catalyze the conversion of ketones and
      cyclic ketones into esters and lactones, respectively. Cyclohexanone
      monooxygenase (CHMO) from Acinetobacter sp. NCIMB 9871 is known to show an
      impressive substrate scope as well as exquisite chemo-, regio-, and
      enantioselectivity in many cases. Large-scale synthetic applications of CHMO are
      hampered, however, by the instability of the enzyme. Oxidation of cysteine and
      methionine residues contributes to this instability. Designed mutations of all
      the methionine and cysteine residues in the CHMO wild type (WT) showed that the
      amino acids labile towards oxidation are mostly either surface-exposed or located
      within the active site, whereas the two methionine residues identified for
      thermostabilization are buried within the folded protein. Combinatorial mutations
      gave rise to two stabilized mutants with either oxidative or thermal stability,
      without compromising the activity or stereoselectivity of the enzyme. The most
      oxidatively stabilized mutant retained nearly 40 % of its activity after
      incubation with H(2)O(2) (0.2 M), whereas the wild-type enzyme's activity was
      completely abolished at concentrations as low as 5 mM H(2)O(2). We propose that
      oxidation-stable mutants might well be a "prerequisite" for thermostabilization,
      because laboratory-evolved thermostability in CHMO might be masked by a high
      degree of oxidation instability.

PMID- 21080397
TI  - Genome mining reveals trans-AT polyketide synthase directed antibiotic
      biosynthesis in the bacterial phylum bacteroidetes.

PMID- 21080398
TI  - Photochemical water decomposition in the troposphere: DFT study with a
      symmetrized Kohn-Sham formalism.
AB  - Photochemical reaction of the electronically excited NO(2)* species with the
      water molecule is studied in terms of a new version of density functional theory
      by selecting the specific (2)A'' symmetry of the whole system, which is different
      from the ground-state pattern. The excited C(2)A(2) state of the NO(2) molecule
      is found to be distorted to the equilibrium structure O=N-O(.), which poses the
      (2)A'' symmetry in the C(s) point group. With the B3LYP functional it is shown
      that such an electronically excited NO(2)* molecule, generated by visible light
      (lambda=420 nm), can react with water vapor to produce OH+HONO species, an
      important source of tropospheric hydroxyl radicals. This photochemical process
      can be considered as a possible mechanism of atmosphere self-cleaning.

PMID- 21080399
TI  - On the relative merits of equilibrium and non-equilibrium simulations for the
      estimation of free-energy differences.
AB  - The possibility of estimating equilibrium free-energy profiles from multiple non
      equilibrium simulations using the fluctuation-dissipation theory or the relation
      proposed by Jarzynski has attracted much attention. Although the Jarzynski
      estimator has poor convergence properties for simulations far from equilibrium,
      corrections have been derived for cases in which the work is Gaussian
      distributed. Here, we examine the utility of corrections proposed by Gore and
      collaborators using a simple dissipative system as a test case. The system
      consists of a single methane-like particle in explicit water. The Jarzynski
      equality is used to estimate the change in free energy associated with pulling
      the methane particle a distance of 3.9 nm at rates ranging from ~0.1 to 100 m s(
      1). It is shown that although the corrections proposed by Gore and collaborators
      have excellent numerical performance, the profiles still converge slowly. Even
      when the corrections are applied in an ideal case where the work distribution is
      necessarily Gaussian, performing simulations under quasi-equilibrium conditions
      is still most efficient. Furthermore, it is shown that even for a single methane
      molecule in water, pulling rates as low as 1 m s(-1) can be problematic. The
      implications of this finding for studies in which small molecules or even large
      biomolecules are pulled through inhomogeneous environments at similar pulling
      rates are discussed.

PMID- 21080400
TI  - Melt electrospinning.
AB  - Melt electrospinning is relatively under-investigated compared to solution
      electrospinning but provides opportunities in numerous areas, in which solvent
      accumulation or toxicity are a concern. These applications are diverse, and
      provide a broad set of challenges to researchers involved in electrospinning. In
      this context, melt electrospinning provides an alternative approach that bypasses
      some challenges to solution electrospinning, while bringing new issues to the
      forefront, such as the thermal stability of polymers. This Focus Review describes
      the literature on melt electrospinning, as well as highlighting areas where both
      melt and solution are combined, and potentially merge together in the future.

PMID- 21080401
TI  - Biradicaloid character of thiophene-based heterophenoquinones: the role of
      electron-phonon coupling.
AB  - The quinoidal versus biradicaloid character of the ground state of a series of
      thiophene-based heterophenoquinones is investigated with quantum-chemical
      calculations. The role of the ground-state electronic character on molecular
      structure and vibrational properties is emphasized. The vibrational activities
      are experimentally determined and their analysis is performed by taking advantage
      of the definition of a collective vibrational coordinate (the R coordinate)
      maximizing the electron-phonon coupling, and connecting the quinoid and the
      aromatic biradicaloid resonance structures. The combined experimental and
      computational investigation supports the biradicaloid nature of the longer
      oligomers. The modulation of Raman intensities and frequency dispersion,
      experimentally observed by increasing the length of the chromophore, is shown to
      be reproduced well by model calculations on a single chromophore as a function of
      geometry displacements along the R-mode. These results underline the role of
      electron-phonon coupling in governing the structure-property relationship of
      highly conjugated organic compounds, underscoring the similarity of thiophene
      heterophenoquinone systems with other, more classical, oligophenylene and
      oligothiophene derivatives.

PMID- 21080402
TI  - The origin and dynamics of soft X-ray-excited optical luminescence of ZnO.
AB  - The distinct optical emission from ZnO materials, nanoneedles and
      microcrystallites synthesized with different sizes and morphologies by a flow
      deposition technique, is investigated with X-ray excited optical luminescence
      (XEOL) and time-resolved X-ray excited optical luminescence (TR-XEOL) from a
      synchrotron light source at the O K and Zn L(3,2) edges. The innovative use of
      XEOL, allowing site-specific chemical information and luminescence information at
      the same time, is fundamental to provide direct evidence for the different
      behaviour and the crucial role of bulk and surface defects in the origin of ZnO
      optical emission, including dynamics. XEOL from highly crystalline ZnO
      nanoneedles is characterized by a sharp band-gap emission (~380 nm) and a broad
      red luminescence (~680 nm) related to surface defects. Luminescence from ZnO
      microcrystallites is mostly dominated by green emission (~510 nm) associated with
      defects in the core. TR-XEOL experiments show considerably faster decay dynamics
      in nanoneedles compared to microcrystallites for both band-gap emission and
      visible luminescence. Herein we make a fundamental step forward correlating for
      the first time the interplay of size, crystallinity, morphology and excitation
      energy with luminescence from ZnO materials.

PMID- 21080404
TI  - Solid-phase total synthesis of (-)-apratoxin A and its analogues and their
      biological evaluation.
AB  - Two approaches for the solid-phase total synthesis of apratoxin A and its
      derivatives were accomplished. In synthetic route A, the peptide was prepared by
      the sequential coupling of the corresponding amino acids on trityl chloride
      SynPhase Lanterns. After cleavage from the polymer-support, macrolactamization of
      10, followed by thiazoline formation, provided apratoxin A. This approach,
      however, resulted in low yield because the chemoselectivity was not sufficient
      for the formation of the thiazoline ring though its analogue 33 was obtained.
      However, in synthetic route B, a cyclization precursor was prepared by solid
      phase peptide synthesis by using amino acids 13-15 and 18. The final
      macrolactamization was performed in solution to provide apratoxin A in high
      overall yield. This method was then successfully applied to the synthesis of
      apratoxin analogues. The cytotoxic activity of the synthetic derivatives was then
      evaluated. The epimer 34 was as potent as apratoxin A, and O-methyl tyrosine can
      be replaced by 7-azidoheptyl tyrosine without loss of activity. The 1,3-dipolar
      cycloaddition of 38 with phenylacetylene was performed in the presence of a
      copper catalyst without affecting the thiazoline ring.

PMID- 21080405
TI  - Nanosizing and nanoconfinement: new strategies towards meeting hydrogen storage
      goals.
AB  - Hydrogen is expected to play an important role as an energy carrier in a future,
      more sustainable society. However, its compact, efficient, and safe storage is an
      unresolved issue. One of the main options is solid-state storage in hydrides.
      Unfortunately, no binary metal hydride satisfies all requirements regarding
      storage density and hydrogen release and uptake. Increasingly complex hydride
      systems are investigated, but high thermodynamic stabilities as well as slow
      kinetics and poor reversibility are important barriers for practical application.
      Nanostructuring by ball-milling is an established method to reduce crystallite
      sizes and increase reaction rates. Since five years attention has also turned to
      alternative preparation techniques that enable particle sizes below 10 nanometers
      and are often used in conjunction with porous supports or scaffolds. In this
      Review we discuss the large impact of nanosizing and -confinement on the hydrogen
      sorption properties of metal hydrides. We illustrate possible preparation
      strategies, provide insight into the reasons for changes in kinetics,
      reversibility and thermodynamics, and highlight important progress in this field.
      All in all we provide the reader with a clear view of how nanosizing and 
      confinement can beneficially affect the hydrogen sorption properties of the most
      prominent materials that are currently considered for solid-state hydrogen
      storage.

PMID- 21080406
TI  - Prenatal ethanol exposure enhances NMDAR-dependent long-term potentiation in the
      adolescent female dentate gyrus.
AB  - The dentate gyrus (DG) is a region of the hippocampus intimately involved with
      learning and memory. Prenatal exposure to either stress or ethanol can reduce
      long-term potentiation (LTP) in the male hippocampus but there is little
      information on how these prenatal events affect LTP in the adolescent female
      hippocampus. Previous studies suggest that deleterious effects of PNEE can, in
      part, be mediated by corticosterone, suggesting that prenatal stress might
      further enhance any alterations to LTP induced PNEE. When animals were exposed to
      a combination of prenatal stress and PNEE distinct sex differences emerged.
      Exposure to ethanol throughout gestation significantly reduced DG LTP in
      adolescent males but enhanced LTP in adolescent females. Combined exposure to
      stress and ethanol in utero reduced the ethanol-induced enhancement of LTP in
      females. On the other hand, exposure to stress and ethanol in utero did not alter
      the ethanol-induced reduction of LTP in males. These results indicate that
      prenatal ethanol and prenatal stress produce sex-specific alterations in synaptic
      plasticity in the adolescent hippocampus.

PMID- 21080407
TI  - Control of anterodorsal thalamic head direction cells by environmental
      boundaries: comparison with conflicting distal landmarks.
AB  - Experiments were conducted to determine whether environmental boundaries exert
      preferential control over the tuning of head direction (HD) cells. In each
      experiment, HD cells were recorded in the rat anterodorsal thalamus while they
      foraged for randomly scattered food in trapezoid- and rectangle-shaped
      environments. After an initial recording session, each environment was rotated 90
      degrees , and changes in the preferred firing directions of HD cells were
      monitored. Rats were disoriented before each test session to prevent the use of
      self-movement cues to maintain orientation from one session to the next. In
      Experiment 1, we demonstrate that HD cell tuning consistently shifted in register
      with the trapezoid shaped enclosure, but was more variable in the rectangle
      shaped environment. In Experiments 2 and 3, we show that the strong control by
      the trapezoid persists in the presence of one clearly visible distal landmark,
      but not when three or more distal landmarks, including view of the recording
      room, are present. Together, the results indicate that distinct environmental
      boundaries exert strong stimulus control over HD cell orientation. However, this
      geometric control can be overridden with a sufficient number of salient distal
      landmarks. These results stand in contrast to the view that information from
      geometric cues usually takes precedence over information from landmark cues.

PMID- 21080408
TI  - Hippocampal gene profiling: toward a systems biology of the hippocampus.
AB  - Transcriptomics and proteomics approaches give a unique perspective for
      understanding brain and hippocampal functions but also pose unique challenges
      because of the singular complexity of the nervous system. The proliferation of
      genome-wide expression studies during the last decade has provided important
      insight into the molecular underpinnings of brain anatomy, neural plasticity, and
      neurological diseases. Microarray technology has dominated transcriptomics
      research, but this situation is rapidly changing with the recent technological
      advances in high-throughput sequencing. The full potential of transcriptomics in
      the neurosciences will be achieved as a result of its integration with other "
      omics" disciplines as well as the development of novel analytical bioinformatics
      and systems biology tools for meta-analysis. Here, we review some of the most
      relevant advances in the gene profiling of the hippocampus, its relationship with
      proteomics approaches, and the promising perspectives for the future.

PMID- 21080409
TI  - Quantitatively and qualitatively different cellular processes are engaged in CA1
      during the consolidation and reconsolidation of contextual fear memory.
AB  - Whether the consolidation and reconsolidation long-term memory relies on
      qualitatively different molecular and cellular processes is controversial. Using
      a novel experimental strategy of combining intrahippocampal antisense
      oligodeoxynucleotides targeting BDNF or zif268 to the block consolidation or
      reconsolidation of contextual fear memory respectively, and Affymetrix microarray
      technology, we identified a comprehensive list of nonoverlapping candidate genes
      regulated in CA1 during the initial stages consolidation and reconsolidation.
      Using RT-qPCR in subsequent validation experiments, we estimated that over 80% of
      the candidates reflect gene transcripts truly regulated following the acquisition
      or retrieval of contextual fear memory. Statistical and over-representation
      bioinformatics analyses revealed that cellular processes and signaling mechanisms
      were differentially regulated during consolidation and reconsolidation,
      particularly those associated with pro-inflammatory cytokine signaling. This
      predicts that the two mnemonic processes are qualitatively as well as
      quantitatively distinct. This experimental strategy was further validated because
      the cytokine interleukin 1 (IL-1) was reciprocally regulated in CA1 after
      contextual fear conditioning and fear memory retrieval, and we showed for the
      first time that that IL-1 receptor mediated signaling in the hippocampus was
      necessary for reconsolidation.

PMID- 21080410
TI  - Increased adult hippocampal neurogenesis and abnormal migration of adult-born
      granule neurons is associated with hippocampal-specific cognitive deficits in
      phospholipase C-beta1 knockout mice.
AB  - Schizophrenia is a devastating psychiatric illness with a complex
      pathophysiology. We have recently documented schizophrenia-like endophenotypes in
      phospholipase C-beta1 knockout (PLC-beta1(-/-)) mice, including deficits in
      prepulse inhibition, hyperlocomotion, and cognitive impairments. PLC-beta1
      signals via multiple G-protein coupled receptor pathways implicated in neural
      cellular plasticity; however, adult neurogenesis has yet to be explored in this
      knockout model. In this study, we employed PLC-beta1(-/-) mice to elucidate
      possible correlates between aberrant adult hippocampal neurogenesis (AHN) and
      schizophrenia-like behaviors. Using stereology and bromodeoxyuridine (BrdU)
      immunohistochemistry we demonstrated a significant increase in the density of
      adult-generated cells in the granule cell layer (GCL) of adult PLC-beta1(-/-)
      mice compared with wild-type littermates. Cellular phenotype analysis using
      confocal microscopy revealed these cells to be mature granule neurons expressing
      NeuN and calbindin. Increased neuronal survival occurred concomitant with reduced
      caspase-3(+) cells in the GCL of PLC-beta1(-/-) mice. Stereological analysis of
      Ki67(+) cells in the subgranular zone suggested that neural precursor
      proliferation is unchanged in PLC-beta1(-/-) mice. We further showed aberrant
      migration of mature granule neurons within the GCL of adult PLC-beta1(-/-) mice
      with excessive adult-generated mature neurons residing in the middle and outer
      GCL. PLC-beta1(-/-) mice exhibited specific behavioral deficits in location
      recognition, a measure of hippocampal-dependent memory, but not novel object
      recognition. Overall, we have shown that PLC-beta1(-/-) mice have a threefold
      increase in net AHN, and have provided further evidence to suggest a specific
      deficit in hippocampal-dependent cognition. We propose that abnormal cellular
      plasticity in these mice may contribute to their schizophrenia-like behavioral
      endophenotypes.

PMID- 21080411
TI  - Spatial representations in dorsal hippocampal neurons during a tactile-visual
      conditional discrimination task.
AB  - Trajectory-dependent coding in dorsal CA1 of hippocampus has been evident in
      various spatial memory tasks aiming to model episodic memory. Hippocampal neurons
      are considered to be trajectory-dependent if the neuron has a place field located
      on an overlapping segment of two trajectories and exhibits a reliable difference
      in firing rate between the two trajectories. It is unclear whether trajectory
      dependent coding in hippocampus is a mechanism used by the rat to solve spatial
      memory tasks. A first step in answering this question is to compare results
      between studies using tasks that require spatial working memory and those that do
      not. We recorded single units from dorsal CA1 of hippocampus during performance
      of a discrete-trial, tactile-visual conditional discrimination (CD) task in a T
      maze. In this task, removable floor inserts that differ in texture and appearance
      cue the rat to visit either the left or right goal arm to receive a food reward.
      Our goal was to assess whether trajectory coding would be evident in the CD task.
      Our results show that trajectory coding was rare in the CD task, with only 12 of
      71 cells with place fields on the maze stem showing a significant firing rate
      difference between left and right trials. For comparison, we recorded from dorsal
      CA1 during the acquisition and performance of a continuous spatial alternation
      task identical to that used in previous studies and found a proportion of
      trajectory coding neurons similar to what has been previously reported. Our data
      suggest that trajectory coding is not a universal mechanism used by the
      hippocampus to disambiguate similar trajectories, and instead may be more likely
      to appear in tasks that require the animal to retrieve information about a past
      trajectory, particularly in tasks that are continuous rather than discrete in
      nature.

PMID- 21080412
TI  - Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled
      adenosine A(2A)  receptors.
AB  - Phosphorylation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptors by Protein Kinase A (PKA) is known to regulate AMPA
      receptor (AMPAR) trafficking and stabilization at the postsynaptic membrane,
      which in turn is one of the key mechanisms by which synaptic transmission and
      plasticity are tuned. However, not much is known as to how Gs-coupled receptors
      contribute to endogenous PKA-mediated regulation of AMPA receptor function. Here
      we report that activation of the excitatory A(2A) adenosine receptor by 2-[4-(2-p
      carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680, 1-30 nM)
      facilitates AMPA-evoked currents in CA1 pyramidal neurons, by a mechanism
      dependent on PKA activation, but not on protein synthesis. This modulation of
      AMPA currents was mimicked by forskolin (1 MUM) and did not occur in stratum
      radiatum interneurons. Superfusion of the A(2A) receptor agonist also caused an
      increase in the amplitude of miniature excitatory postsynaptic currents (mEPSCs),
      as well as in the membrane levels of GluR1 subunits phosphorylated at the PKA
      site (Ser845). The impact of this increase on GluR1-containing AMPA receptor
      expression was evidenced by the potentiation of LTP at the CA3-CA1 synapse that
      followed brief activation of A(2A) receptors. We thus propose that in conditions
      of increased adenosine availability, A(2A) receptor activation is responsible for
      setting part of the endogenous GluR1 Ser-845 phosphorylation tonus and hence, the
      availability of the GluR1-containing AMPA receptor extrasynaptic pool for
      synaptic insertion and reinforcement of synaptic strength.

PMID- 21080413
TI  - Cellular basis of a rapid effect of mineralocorticosteroid receptors activation
      on LTP in ventral hippocampal slices.
AB  - The ventral hippocampus (VH) was recently shown to express lower magnitude LTP
      compared to the dorsal hippocampus (DH). Exposure to acute stress reversed this
      difference, and VH slices from stressed rats expressed larger LTP than that
      produced in the DH, which was reduced by stress. In an attempt to uncover the
      mechanisms responsible for this differential action, we found that activation of
      mineralocorticosteroid receptors (MR) by aldosterone mimics the effects of stress
      in the VH, to facilitate LTP. We also found that aldosterone reduces GABAergic
      inhibition in both the DH and VH. We now examined if the reduction in inhibition
      caused by MRs can underlie the altered LTP in the VH. Rat hippocampal slices were
      recorded before and after exposure to the GABA antagonist bicuculline and to
      aldosterone. As expected, blockade of GABA with bicuculline enhanced LTP in both
      DH and VH. However, its effect did not occlude that of aldosterone in the VH,
      indicating that the latter drug does not operate by blockade of inhibition.
      Furthermore, the NMDA receptor antagonist APV blocked LTP induced in the presence
      of bicuculline, but did not block LTP facilitation by aldosterone, indicating
      that the effect of aldosterone is not mediated by the conventional NMDA-dependent
      LTP generating mechanism. Furthermore, rapid effects of aldosterone on LTP were
      blocked by the L-type calcium channel antagonist nifedipine, indicating that
      aldosterone facilitates calcium influx via nifedipine-sensitive channels, to
      enhance LTP in the VH. The locus of effect of aldosterone may be the presynaptic
      terminal, as it caused a marked facilitation of paired pulse potentiation in the
      VH but not in the DH. These experiments confirm and extend previous suggestions
      for the effects of MRs on neuronal plasticity in the hippocampus.

PMID- 21080416
TI  - Acamprosate in the treatment of binge eating disorder: a placebo-controlled
      trial.
AB  - OBJECTIVE: To assess preliminarily the effectiveness of acamprosate in binge
      eating disorder (BED). METHOD: In this 10-week, randomized, placebo-controlled,
      flexible dose trial, 40 outpatients with BED received acamprosate (N = 20) or
      placebo (N = 20). The primary outcome measure was binge eating episode frequency.
      RESULTS: While acamprosate was not associated with a significantly greater rate
      of reduction in binge eating episode frequency or any other measure in the
      primary longitudinal analysis, in the endpoint analysis it was associated with
      statistically significant improvements in binge day frequency and measures of
      obsessive-compulsiveness of binge eating, food craving, and quality of life.
      Among completers, weight and BMI decreased slightly in the acamprosate group but
      increased in the placebo group. DISCUSSION: Although acamprosate did not separate
      from placebo on any outcome variable in the longitudinal analysis, results of the
      endpoint and completer analyses suggest the drug may have some utility in BED.

PMID- 21080422
TI  - Structures of the first and second double-stranded RNA-binding domains of human
      TAR RNA-binding protein.
AB  - The TAR RNA-binding Protein (TRBP) is a double-stranded RNA (dsRNA)-binding
      protein, which binds to Dicer and is required for the RNA interference pathway.
      TRBP consists of three dsRNA-binding domains (dsRBDs). The first and second
      dsRBDs (dsRBD1 and dsRBD2, respectively) have affinities for dsRNA, whereas the
      third dsRBD (dsRBD3) binds to Dicer. In this study, we prepared the single domain
      fragments of human TRBP corresponding to dsRBD1 and dsRBD2 and solved the crystal
      structure of dsRBD1 and the solution structure of dsRBD2. The two structures
      contain an alpha-beta-beta-beta-alpha fold, which is common to the dsRBDs. The
      overall structures of dsRBD1 and dsRBD2 are similar to each other, except for a
      slight shift of the first alpha helix. The residues involved in dsRNA binding are
      conserved. We examined the small interfering RNA (siRNA)-binding properties of
      these dsRBDs by isothermal titration colorimetry measurements. The dsRBD1 and
      dsRBD2 fragments both bound to siRNA, with dissociation constants of 220 and 113
      nM, respectively. In contrast, the full-length TRBP and its fragment with dsRBD1
      and dsRBD2 exhibited much smaller dissociation constants (0.24 and 0.25 nM,
      respectively), indicating that the tandem dsRBDs bind simultaneously to one siRNA
      molecule. On the other hand, the loop between the first alpha helix and the first
      beta strand of dsRBD2, but not dsRBD1, has a Trp residue, which forms hydrophobic
      and cation-pi interactions with the surrounding residues. A circular dichroism
      analysis revealed that the thermal stability of dsRBD2 is higher than that of
      dsRBD1 and depends on the Trp residue.

PMID- 21080423
TI  - Structure of Sir2Tm bound to a propionylated peptide.
AB  - Lysine propionylation is a recently identified post-translational modification
      that has been observed in proteins such as p53 and histones and is thought to
      play a role similar to acetylation in modulating protein activity. Members of the
      sirtuin family of deacetylases have been shown to have depropionylation activity,
      although the way in which the sirtuin catalytic site accommodates the bulkier
      propionyl group is not clear. We have determined the 1.8 A structure of a
      Thermotoga maritima sirtuin, Sir2Tm, bound to a propionylated peptide derived
      from p53. A comparison with the structure of Sir2Tm bound to an acetylated
      peptide shows that hydrophobic residues in the active site shift to accommodate
      the bulkier propionyl group. Isothermal titration calorimetry data show that
      Sir2Tm binds propionylated substrates more tightly than acetylated substrates,
      but kinetic assays reveal that the catalytic rate of Sir2Tm deacylation of
      propionyl-lysine is slightly reduced to acetyl-lysine. These results serve to
      broaden our understanding of the newly identified propionyl-lysine modification
      and the ability of sirtuins to depropionylate, as well as deacetylate,
      substrates.

PMID- 21080424
TI  - Site-specific 19F NMR chemical shift and side chain relaxation analysis of a
      membrane protein labeled with an unnatural amino acid.
AB  - Site-specific 19F chemical shift and side chain relaxation analysis can be
      applied on large size proteins. Here, one-dimensional 19F spectra and T1, T2
      relaxation data were acquired on a SH3 domain in aqueous buffer containing 60%
      glycerol, and a nine-transmembrane helices membrane protein diacyl-glycerol
      kinase (DAGK) in dodecyl phosphochoine (DPC) micelles. The high quality of the
      data indicates that this method can be applied to site-specifically analyze side
      chain internal mobility of membrane proteins or large size proteins.

PMID- 21080425
TI  - Highly efficient purification of protein complexes from mammalian cells using a
      novel streptavidin-binding peptide and hexahistidine tandem tag system:
      application to Bruton's tyrosine kinase.
AB  - Tandem affinity purification (TAP) is a generic approach for the purification of
      protein complexes. The key advantage of TAP is the engineering of dual affinity
      tags that, when attached to the protein of interest, allow purification of the
      target protein along with its binding partners through two consecutive
      purification steps. The tandem tag used in the original method consists of two
      IgG-binding units of protein A from Staphylococcus aureus (ProtA) and the
      calmodulin-binding peptide (CBP), and it allows for recovery of 20-30% of the
      bait protein in yeast. When applied to higher eukaryotes, however, this classical
      TAP tag suffers from low yields. To improve protein recovery in systems other
      than yeast, we describe herein the development of a three-tag system comprised of
      CBP, streptavidin-binding peptide (SBP) and hexa-histidine. We illustrate the
      application of this approach for the purification of human Bruton's tyrosine
      kinase (Btk), which results in highly efficient binding and elution of bait
      protein in both purification steps (>50% recovery). Combined with mass
      spectrometry for protein identification, this TAP strategy facilitated the first
      nonbiased analysis of Btk interacting proteins. The high efficiency of the SBP
      His6 purification allows for efficient recovery of protein complexes formed with
      a target protein of interest from a small amount of starting material, enhancing
      the ability to detect low abundance and transient interactions in eukaryotic cell
      systems.

PMID- 21080428
TI  - Characterization of the disordered-to-alpha-helical transition of IA3 by SDSL-EPR
      spectroscopy.
AB  - Electron paramagnetic resonance (EPR) spectroscopy coupled with site-directed
      spin labeling (SDSL) is a valuable tool for characterizing the mobility and
      conformational changes of proteins but has seldom been applied to intrinsically
      disordered proteins (IDPs). Here, IA3 is used as a model system demonstrating
      SDSL-EPR characterization of conformational changes in small IDP systems. IA3 has
      68 amino acids, is unstructured in solution, and becomes alpha-helical upon
      addition of the secondary structural stabilizer 2,2,2-trifluoroethanol (TFE). Two
      single cysteine substitutions, one in the N-terminus (S14C) and one in the C
      terminus (N58C), were generated and labeled with three different nitroxide spin
      labels. The resultant EPR line shapes of each of the labels were compared and
      each reported changes in mobility upon addition of TFE. Specifically, the
      spectral line shape parameters h((+1))/h(0), the local tumbling volume (V(L)),
      and the percent change of the h(-1) intensity were utilized to quantitatively
      monitor TFE-induced conformational changes. The values of h((+1)/)h(0) as a
      function of TFE titration varied in a sigmoidal manner and were fit to a two
      state Boltzmann model that provided values for the midpoint of the transition,
      thus, reporting on the global conformational change of IA3. The other parameters
      provide site-specific information and show that S14C-SL undergoes a
      conformational change resulting in more restricted motion than N58C-SL, which is
      consistent with previously published results obtained by studies using NMR and
      circular dichroism spectroscopy indicating a higher degree of alpha-helical
      propensity of the N-terminal segment of IA3. Overall, the results provide a
      framework for data analyzes that can be used to study induced unstructured-to
      helical conformations in IDPs by SDSL.

PMID- 21080437
TI  - Author's reply to: Multiple human papillomavirus genotype infections in cervical
      cancer progression in the study to understand cervical cancer early endpoints and
      determinants.

PMID- 21080439
TI  - Autophagy-mediated chemosensitization by cysteamine in cancer cells.
AB  - Cysteamine (CS) has many biomedical and clinical applications because of its
      excellent water solubility, low cytotoxicity and good biocompatibility. A
      previous study by Brawer et al. reported the occurrence of many Gomori inclusion
      bodies in CS-treated astrocytes, which would suggest the induction of autophagy.
      Here we provided a comprehensive line of evidence demonstrating that CS caused
      autophagosome accumulation in cancer cells. CS exerted a biphasic effect on the
      autophagy process, increasing the formation of autophagosomes in the early phase
      and blocking the autophagic degradation in a later phase. Furthermore, we showed
      that CS sensitized doxorubicin-elicited chemotherapeutic killing in HeLa, B16
      melanoma and doxorubicin-resistant MCF-7 cells and also enhanced chemotherapeutic
      efficacy of doxorubicin in a mouse melanoma model. Finally, we demonstrated that
      the chemosensitizing effect of CS was at least partly dependent on its ability to
      modulate autophagy. Our results revealed a novel biological function for CS in
      enhancing the chemotherapeutic effect of doxorubicin through autophagy modulation
      and pointed to the potential use of CS in adjunct cancer chemotherapy.

PMID- 21080441
TI  - Electrospun nanofibrous polycaprolactone scaffolds for tissue engineering of
      annulus fibrosus.
AB  - The annulus fibrosus comprises concentric lamellae that can be damaged due to
      intervertebral disc degeneration; to provide permanent repair of these acquired
      structural defects, one solution is to fabricate scaffolds that are designed to
      support the growth of annulus fibrosus cells. In this study, electrospun
      nanofibrous scaffolds of polycaprolactone are fabricated in random, aligned, and
      round-end configurations. Primary porcine annulus fibrosus cells are grown on the
      scaffolds and evaluated for attachment, proliferation, and production of
      extracellular matrix. The scaffold consisting of round-end nanofibers
      substantially outperforms the random and aligned scaffolds on cell adhesion;
      additionally, the scaffold with aligned nanofibers strongly affects the
      orientation of cells.

PMID- 21080442
TI  - Association between sleep duration and body size differs among three Hispanic
      groups.
AB  - OBJECTIVES: Although numerous studies have reported negative associations between
      sleep duration and body size, no studies of this association have focused on
      Hispanic groups, which was the goal of this work. METHODS: Data are from adults
      in the 1982-1984 Hispanic Health and Nutrition Examination Survey (HHANES), which
      enrolled Cuban-Americans, Mexican-Americans, and Puerto Ricans. HHANES included
      self-reported sleep duration and several anthropometric measures. Principle
      component analysis extracted a single variable to represent body size. Linear
      regression models stratified by Hispanic group predicted body size from sleep
      duration adjusting for age, sex, education, income, marital status, household
      size, and acculturation. RESULTS: Average age was 36-44 years and 52-64% were
      women. Average sleep duration was 7.3-7.7 h. Shorter sleep duration was
      associated with larger body size in Mexican-Americans only. The regression
      coefficient indicated that on average a Mexican-American adult who reported
      sleeping for 4 h would have a body size that was larger by 0.12 times the
      standard deviation for body size than a Mexican-American adult reporting 8 h of
      sleep (all other covariates being equal). This effect was similar to the effect
      of 10 years of age, which would be associated with an increase in body size by
      0.10 times the standard deviation of body size. CONCLUSIONS: These results
      underscore the importance of examining factors associated with obesity in
      different ethnic groups. It may be inappropriate to combine different Hispanic
      ethnicities together.

PMID- 21080444
TI  - Parental investment and socioeconomic status influences on children's height in
      Honduras: An analysis of national data.
AB  - OBJECTIVES: This research analyzes variation in children's height-for-age z
      scores from a nationally representative sample of children from Honduras in 2006.
      This work draws on theoretical perspectives from parental investment theory to
      describe the mediating effects that parental investment may have on children's
      health and nutrition, even in low socioeconomic status households. METHODS: This
      research uses the 2006 Demographic and Health Survey for the country of Honduras.
      The dependent variable is the child's height-for-age z-score (HFAZ). Variation in
      the HFAZ is analyzed using multiple regression and multilevel regression models
      to incorporate individual, family and higher-level predictors. RESULTS: The
      findings suggest that children who are more invested in by their parents had
      better outcomes (HFAZ) than children whose parents did not invest as much. Of the
      three measures of parental investment used in this study, child wantedness and
      adequate prenatal care represented significant effects on children's HFAZ, and
      breastfeeding duration exhibited an interactive effect with household
      socioeconomic status. CONCLUSIONS: Results suggest that families that can invest
      more in their children through breastfeeding and sufficient prenatal care can
      mediate the negative effects of poor socioeconomic status on their children's
      health. This suggests that these measures of investment used here may be
      effective at mediating the negative effects of low socioeconomic status for this
      particular child health outcome.

PMID- 21080443
TI  - Exposure to professional pest control treatments and the risk of childhood acute
      lymphoblastic leukemia.
AB  - Previous studies suggest that exposure to pesticides increases the risk of
      childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to
      investigate whether professional pest treatments in or around the home before
      birth or during childhood increased the risk of childhood ALL. Data from 388
      cases and 870 frequency-matched controls were analyzed using unconditional
      logistic regression, adjusting for study matching variables and potential
      confounders, to calculate odds ratios (ORs). A meta-analysis of our findings with
      the published findings of previous studies was also conducted. The ORs for any
      professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year
      before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI
      0.93, 1.65) for those done after the child's birth. The ORs for exposure after
      birth were highest when it occurred between the ages of two and three years. ORs
      were elevated for termite treatments before birth. ORs were higher for pre-B than
      T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. The
      pooled OR from a meta-analysis of our study with three previous studies of
      professional pest control treatments during pregnancy was 1.37 (95% CI 1.00,
      1.88). Our results, and those of our meta-analysis, provide some evidence of a
      modestly increased risk of ALL for professional pest control treatments done
      during the index pregnancy and possibly in the child's early years. The analysis
      of pooled data from international collaborations may provide more certainty
      regarding these potentially important associations.

PMID- 21080445
TI  - Maternal fetal interaction in the ABO system: A comparative analysis of healthy
      mother and couples with spontaneous abortion in Bengalee population.
AB  - OBJECTIVES: The selective effects on genotypes could generally be perceived by
      its manifestation in prezygotic and postzygotic stages, which is further
      extendable to neonatal and postnatal periods in human. Selective elimination of
      genotypes could generally be perceived by the study of reproductive performance
      of the couple on the basis of their mating types. Actual studies on the products
      of conception, living, or dead (aborted material) of these couples essential for
      understanding of process of selective elimination of the alleles. METHODS: Of 124
      spontaneous abortions occurring during the first 16 weeks of gestation,
      simultaneous karyotyping and ABO blood grouping of 148 of the parents was carried
      out. In 80 of the 124 chromosome-analyzed aborted foeti, the ABO blood groups of
      the foeti were determined by the mixed cell agglutinating reaction in fetal
      tissue. RESULTS: The results of the ABO blood grouping were compared with that of
      100 newborns along with their parents (181) from the same area. Among aborted
      foeti with normal karyotype, a significantly higher (P < 0.05) frequency of ABO
      incompatibility was found in couple combination in comparison with the couple
      combination of the parents of the newborns. Furthermore, the distribution ABO
      blood group alleles of the fetuses deviated significantly from those of newborns
      (P < 0.05) in terms of significantly higher A alleles among the fetus.
      CONCLUSIONS: The ABO incompatibility between the couples is likely to be a risk
      factor for early spontaneous abortions and also the heterozygote selection of ABO
      blood group genotypes.

PMID- 21080446
TI  - Contraceptive counseling and use among women with systemic lupus erythematosus: a
      gap in health care quality?
AB  - OBJECTIVE: Disease activity and medication use can complicate pregnancies in
      patients with systemic lupus erythematosus (SLE). We therefore examined
      contraceptive counseling and use among women in the University of California, San
      Francisco Lupus Outcomes Study. METHODS: In 2008, we queried participants
      regarding their pregnancy intentions, contraceptive use, and receipt of
      contraceptive counseling. Premenopausal women age <45 years who were sexually
      active with men were considered at risk of pregnancy. We compared self-reported
      rates of contraceptive counseling and use stratified by treatment with
      teratogenic medications and by history of thrombosis or antiphospholipid
      antibodies (aPL), using chi-square tests. We used logistic regression models to
      examine predictors of contraceptive counseling and use. RESULTS: Among 206 women,
      86 were at risk for unplanned pregnancy. Most (59%) had not received
      contraceptive counseling in the last year, 22% reported inconsistent
      contraceptive use, and 53% depended solely on barrier methods. Intrauterine
      device contraceptives (IUDs) were used by 13%. Women using potentially
      teratogenic medications were no more likely to have received contraceptive
      counseling, to have used contraception consistently, or to have used more
      effective contraceptives. A history of thrombosis or aPL did not account for low
      rates of hormonal methods. Four women with a history of thrombosis or aPL were
      using estrogen-containing contraceptives. CONCLUSION: Most women at risk for
      unplanned pregnancy reported no contraceptive counseling in the past year,
      despite common use of potentially teratogenic medications. Many relied upon
      contraceptive methods with high failure rates; few used IUDs. Some were
      inappropriately using estrogen-containing contraceptives. These findings suggest
      the need to improve the provision of contraceptive services to women with SLE.

PMID- 21080449
TI  - Treatment and nontreatment predictors of health assessment questionnaire
      disability progression in rheumatoid arthritis: a longitudinal study of 18,485
      patients.
AB  - OBJECTIVE: To examine predictors of progression of disability in rheumatoid
      arthritis (RA), as measured by the Health Assessment Questionnaire disability
      index (HAQ), and to determine rates of progression during biologic treatment.
      METHODS: We followed 18,485 RA patients for up to 11 years (mean 3.7 years) in a
      longitudinal study of RA outcomes. Patients were characterized as having moderate
      or severe RA versus less severe RA at study entry. Annualized progression rates
      were determined in multivariable analyses using generalized estimating equations.
      RESULTS: Although all of the demographic and severity characteristics were
      associated with baseline differences in HAQ score, progression was only
      associated with age, comorbidity, initial severity, and treatment. HAQ score
      increased fastest in patients ages >65 years (0.031; 95% confidence interval [95%
      CI] 0.028, 0.034). HAQ progression was independently associated with the presence
      of baseline cardiovascular disease, hypertension, diabetes mellitus, and the
      number of comorbid conditions. Annualized progression rates were greater in
      patients with mild to inactive RA (0.021; 95% CI 0.019, 0.023) than in moderate
      to severe RA (0.003; 95% CI 0.001, 0.006). The overall progression rate during
      biologic treatment was 0.008 (95% CI 0.005, 0.011); for patients with moderate to
      severe RA, the rate was 0.001 (95% CI -0.005, 0.003). CONCLUSION: Age and
      comorbidity are important predictors of the rate of loss of functional status,
      and have a stronger effect on HAQ progression than does biologic treatment. There
      is little difference in progression rates among biologics. Patients with more
      severe RA progress less than those with less severe RA, a possible function of
      regression to the mean.

PMID- 21080474
TI  - Assessment of Canadian Cree infants' birth size using the WHO Child Growth
      Standards.
AB  - OBJECTIVES: The WHO Child Growth Standards (CGS) which were recently adopted by
      the Canadian Pediatric Society were used to assess the relative size of Cree
      newborns. METHODS: Birth weight, length, and head circumference, and growth
      indices of 2,127 Cree newborns were compared with the CGS. Maternal
      characteristics of pregnancy and infant birth outcomes were recorded and
      stratified by birth weight category. RESULTS: Among Cree newborns, 2.4% were low
      birth weight (LBW) (<2,500 g) and 36.5% were high birth weight (>=4,000 g). The
      median birth weight (g) for Cree male (4,030) and female (3,900) term newborns
      was higher than for male (3,346) and female (3,232) newborns of the CGS. Fewer
      than 1.5% of Cree infants had z-scores <-2SD from the WHO CGS median for BMI-for
      age, length-for-age, weight-for-age, or head circumference-for-age whereas 4.6,
      7.8, and 23.4% percent had z-scores >+2SD from the WHO CGS median for weight-for
      length-for-age, BMI-for-age and head circumference-for-age, respectively. The
      majority (53.4%) of pregnancies was complicated by obesity and 10.3% were
      complicated by gestational diabetes mellitus (GDM). Infants weighing 4,000-4,499
      g had a comparable prevalence of operative delivery (15.4%) as infants weighing
      2,500-3,999 g (13.7%). Infants weighing >=4,500 g had the highest prevalence of
      birth injuries (14.0%) and being born to women whose pregnancies were complicated
      by GDM (20%). CONCLUSIONS: Cree newborns were larger than newborns of the CGS.
      The appropriateness for Cree infants of defining low and high birth weight from
      the WHO CGS is uncertain and may lead to inaccurate prognosis of postnatal
      health.

PMID- 21080475
TI  - Genetic influences on serum bilirubin in American Indians: The Strong Heart
      Family Study.
AB  - OBJECTIVE: To identify genetic variation influencing serum bilirubin levels in
      American Indians, we performed genome-wide screening and association analyses in
      the Strong Heart Family Study. Bilirubin is an endogenous antioxidant that has
      demonstrated an inverse relationship with cardiovascular disease. Genetic
      variation within the promoter region of uridine diphosphate
      glucuronosyltransferase (UGT1A1) on chromosome 2q has been associated with
      elevated serum bilirubin levels in European populations. However, no study has
      investigated the UGT1A1 promoter in American Indians. METHODS: Statistical
      analyses were carried out with 3,484 participants aged 14 to 93 years recruited
      from three geographic areas in the United States; Arizona, Oklahoma, and North
      and South Dakota. RESULTS: Variance components linkage analysis detected a
      quantitative trait locus (QTL) for bilirubin on chromosome 2q in the combined
      centers (LOD = 6.61, P = 4.24 * 10-6) and in Oklahoma (LOD = 5.65, P = 4.57 24 *
      10-5). Genetic association of the UGT1A1 promoter polymorphism was significant
      for all geographic locations. After adjustment using conditional linkage for
      UGT1A1 promoter variance, the linkage signal dropped to 1.10 in the combined
      sample and to 3.32 (P = 0.02) in Oklahoma, indicating this polymorphism is not
      completely responsible for the linkage signal in American Indians. We also
      detected suggestive linkage signals in the Dakotas on chromosome 10p12 (LOD =
      2.18) and in the combined centers (LOD = 2.24) on chromosome 10q21. CONCLUSIONS:
      Replication of a serum bilirubin QTL on chromosome 2q in American Indians
      implicates UGT1A1 but further genotyping is warranted to identify additional
      causative polymorphisms. Evidence also supports a potential novel locus for
      bilirubin on chromosome 10.

PMID- 21080476
TI  - Inverse association between adiposity and telomere length: The Fels Longitudinal
      Study.
AB  - OBJECTIVES: To assess the relationship between telomere length and adiposity,
      using dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging
      (MRI), in addition to conventional anthropometric proxies including body mass
      index (BMI) and cardiovascular disease risk factors. METHODS: A cross-sectional
      sample of 309 non-Hispanic white participants in the Fels Longitudinal Study aged
      8 to 80 yr (52% female) was included. Average telomere length was measured by
      quantitative PCR. RESULTS: Telomere length was negatively correlated with age (r
      = -0.32, P < 0.0001) and had numerous significant correlations with established
      cardiovascular disease risk factors including waist circumference (r = -0.33),
      apolipoprotein B (r = -0.26), systolic blood pressure (r = -0.28), and fasting
      serum glucose (r = -0.15); all P < 0.0025. In backward selection linear
      regression models of telomere length, adiposity measures were consistently
      retained in the best models; BMI, waist circumference, hip circumference, total
      body fat, and visceral adipose tissue volume were all inversely associated with
      telomere length at the nominal P < 0.05 level or lower, independent of age, sex,
      systolic blood pressure, and fasting serum lipid, lipoprotein, and glucose
      concentrations. The negative association of BMI with telomere length was stronger
      among younger than older participants (P for interaction, 0.03). CONCLUSIONS:
      Individuals with higher total and abdominal adiposity have lower telomere length,
      a marker of cellular senescence, suggesting obesity may hasten the aging process.
      Longitudinal studies are required to establish the causal association of early
      life adiposity with biological aging.

PMID- 21080484
TI  - Detection of immunogenic parasite and host-specific proteins in the sera of
      active and chronic individuals infected with Toxoplasma gondii.
AB  - Toxoplasma gondii infection in pregnant women may result in abortion and foetal
      abnormalities, and may be life-threatening in immunocompromised hosts. To
      identify the potential infection markers of this disease, 2-DE and Western blot
      methods were employed to study the parasite circulating antigens and host
      specific proteins in the sera of T. gondii-infected individuals. The comparisons
      were made between serum protein profiles of infected (n=31) and normal (n=10)
      subjects. Antigenic proteins were identified by immunoblotting using pooled sera
      and monoclonal anti-human IgM-HRP. Selected protein spots were characterised
      using mass spectrometry. Prominent differences were observed when serum samples
      of T. gondii-infected individuals and normal controls were compared. A
      significant up-regulation of host-specific proteins, alpha(2)-HS glycoprotein and
      alpha(1)-B glycoprotein, was also observed in the silver-stained gels of both
      active and chronic infections. However, only alpha(2)-HS glycoprotein and
      alpha(1)-B glycoprotein in the active infection showed immunoreactivity in
      Western blots. In addition, three spots of T. gondii proteins were detected,
      namely (i) hypothetical protein chrXII: 3984434-3 TGME 49, (ii) dual specificity
      protein phosphatase, catalytic domain TGME 49 and (iii) NADPH-cytochrome p450
      reductase TGME 49. Thus, 2-DE approach followed by Western blotting has enabled
      the identification of five potential infection markers for the diagnosis of
      toxoplasmosis: three are parasite-specific proteins and two are host-specific
      proteins.

PMID- 21080487
TI  - Subcellular proteomics today.

PMID- 21080485
TI  - Proteomic identification and comparative analysis of asymmetrically arginine
      methylated proteins in immortalized, young and senescent cells.
AB  - Protein-arginine methylation is one of the modifications that yields mono and
      dimethyl (asymmetric or symmetric) arginine residues in proteins. Previously, we
      found that asymmetric arginine methylation is decreased proportionately with a
      decrease of cell proliferation potential of cells, and such arginine methylation
      is greatest in immortalized cells, followed by normal young cells, and lowest in
      replicatively senescent cells. Using an asymmetric dimethyl-arginine-specific
      antibody, we identified arginine-methylated proteins in these cell types by
      immunoprecipitation and 2-D immunoblotting followed by MS. As a result, arginine
      methylation of chaperone molecules and RNA-binding proteins was differentially
      regulated between immortalized or young cells and senescent cells. Immortalized
      cells had significantly higher levels of methyl-accepting proteins, such as
      cleavage stimulation factor 2 (CstF2) and heterogeneous nuclear ribonucleoprotein
      (hnRNP) R, than young cells. However, senescent cells contained hypomethylated
      CstF2, hnRNP K, and chaperone containing TCP1 subunit 7, as well as decreased
      hnRNP R level. Further, significant reduction of arginine modification in CstF2
      and chaperone containing TCP1 subunit 7 was observed in prematurely senescent
      fibroblasts, induced by treatment with adenosine dialdehyde, a transmethylation
      inhibitor, or subcytotoxic concentration of H(2)O(2). These results suggest that
      asymmetric modification of RNA-binding proteins and molecular chaperones plays an
      essential role in maintaining cell proliferation capability.

PMID- 21080488
TI  - Subcellular fractionation methods and strategies for proteomics.
AB  - Developments in subcellular fractionation strategies have provided the means to
      profile and analyze the protein composition of organelles and cellular structures
      by proteomics. Here, we review the application of classical (e.g. density
      gradient centrifugation) and emerging sophisticated techniques (fluorescent
      assisted organelle sorting) in the fractionation, and statistical/bioinformatics
      tools for the prediction of protein localization in subcellular proteomics. We
      also review the validation methods currently used (such as microscopy, RNA
      interference and multiple reaction monitoring) and discuss the importance of
      verification of the results obtained in subcellular proteomics. Finally, the
      numerous challenges facing subcellular proteomics including the dynamics of
      organelles are being examined. However, complementary approaches such as modern
      statistics, bioinformatics and large-scale integrative analysis are beginning to
      emerge as powerful tools to proteomics for analyzing subcellular organelles and
      structures.

PMID- 21080489
TI  - Organelle proteomics experimental designs and analysis.
AB  - In biology, localisation is function: knowledge of the localisation of proteins
      is of paramount importance to assess and study their function. This supports the
      need for reliable protein sub-cellular localisation assignment. Concomitant with
      recent technological advances in organelle proteomics, there is a requirement for
      more rigorous experimental and analysis design planning and description. In this
      review, we present an overview of current experimental designs in qualitative and
      quantitative organelle proteomics as well as associated data analysis. We also
      consider the major benefits associated with careful description and dissemination
      of the experiment and analysis designs, namely (i) comparison and optimisation of
      experimental designs and analysis pipelines, (ii) data validation, (iii)
      reproducible research, (iv) efficient repository submission and retrieval and (v)
      meta analysis. Formalization of experimental design and analysis work flows is of
      direct benefit for the organelle proteomics researchers and will result in
      providing organelle localisation data of highest quality for the wider research
      community.

PMID- 21080490
TI  - Prediction of subcellular locations of proteins: where to proceed?
AB  - Since the proposal of the signal hypothesis on protein subcellular sorting, a
      number of computational analyses have been performed in this field. A typical
      example is the development of prediction algorithms for the subcellular
      localization sites of input protein sequences. In this review, we mainly focus on
      the biological grounds of the prediction methods rather than the algorithmic
      issues because we believe the former will be more fruitful for future
      development. Recent advances on the study of protein sorting signals will
      hopefully be incorporated into future prediction methods. Unfortunately, many of
      the state-of-the-art methods are published without sufficient objective tests. In
      fact, a simple test employed in this article shows that the performance of
      specifically developed predictors is not significantly better than that of a
      homology search. We suspect that this is a general problem associated with the
      interpretation of genome sequences, which have evolved through gene duplication
      and speciation.

PMID- 21080491
TI  - Proteomics and the dynamic plasma membrane: Quo Vadis?
AB  - Quo Vadis: where are you going? Advances in MS-based proteomics have enabled
      research to move from obtaining the basic protein inventory of cells and
      organelles to the ability of monitoring their dynamics, including changes in
      abundance, location and various PTMs. In this respect, the cellular plasma
      membrane is of particular interest, by not only serving as a barrier between the
      "cell interior" and the external environment, but moreover by organizing and
      clustering essential components to enable dynamic responses to internal and
      external stimuli. Defining and characterizing the dynamic plasma membrane
      proteome is crucial for understanding fundamental biological processes, disease
      mechanisms and for finding drug targets. Protein identification, characterization
      of dynamic PTMs and protein-ligand interactions, and determination of transient
      changes in protein expression and composition are among the challenges in
      functional proteomic studies of the plasma membrane. We review the recent
      progress in MS-based plasma membrane proteomics by presenting key examples from
      eukaryotic systems, including mammals, yeast and plants. We highlight the
      importance of enrichment and quantification technologies required for detailed
      functional and comparative analysis of the dynamic plasma membrane proteome.

PMID- 21080492
TI  - Mosaic origin of the mitochondrial proteome.
AB  - Although the origin of mitochondria from the endosymbiosis of an alpha
      proteobacterium is well established, the nature of the host cell, the metabolic
      complexity of the endosymbiont and the subsequent evolution of the proto
      mitochondrion into all its current appearances are still the subject of discovery
      and sometimes debate. Here we review what has been inferred about the original
      composition and subsequent evolution of the mitochondrial proteome and essential
      mitochondrial systems. The evolutionary mosaic that currently constitutes
      mitochondrial proteomes contains (i) endosymbiotic proteins (15-45%), (ii)
      proteins without detectable orthologs outside the eukaryotic lineage (40%), and
      (iii) proteins that are derived from non-proteobacterial Bacteria, Bacteriophages
      and Archaea (15%, specifically multiple tRNA-modification proteins). Protein
      complexes are of endosymbiotic origin, but have greatly expanded with novel
      eukaryotic proteins; in contrast to mitochondrial enzymes that are both of
      proteobacterial and non-proteobacterial origin. This disparity is consistent with
      the complexity hypothesis, which argues that proteins that are a part of large,
      multi-subunit complexes are unlikely to undergo horizontal gene transfer. We
      observe that they neither change their subcellular compartments in the course of
      evolution, even when their genes do.

PMID- 21080493
TI  - Proteomic analysis of clathrin-coated vesicles.
AB  - For more than 50 years cell biologists have embraced the concept that biochemical
      and enzymatic analysis of isolated subcellular fractions provides insight into
      the function and machineries of cellular compartments including organelles. The
      utility of this approach has been significantly enhanced with the advent of mass
      spectrometry leading to the broad application of organelle proteomics. Clathrin
      coated vesicles (CCVs) form at the plasma membrane where they select protein and
      lipid cargo for endocytic entry into cells. CCVs also form at the trans-Golgi
      network, where they function in protein transport from the secretory pathway to
      the endosomal/lysosomal system. Herein we will describe how organelle proteomics
      of CCVs has greatly expanded our knowledge of the machineries, mechanisms and
      sites of clathrin-mediated membrane trafficking.

PMID- 21080495
TI  - p53-Dependent subcellular proteome localization following DNA damage.
AB  - The nucleolus is involved in regulating several aspects of stress responses and
      cell cycle arrest through the tumor suppressor p53. Under normal conditions, p53
      is a short-lived protein that is present in cells at a barely detectable level.
      Upon exposure of cells to various forms of exogenous stress, such as DNA damage,
      there is a stabilization of p53 which is then responsible for an ensuing cascade
      of events. To further investigate the effect of p53 activation, we used a MS
      based proteomics method to provide an unbiased, quantitative and high-throughput
      approach for measuring the subcellular distribution of the proteome that is
      dependent on p53. The spatial proteomics method analyses a whole cell extract
      created by recombining differentially labeled subcellular fractions derived from
      cells in which proteins have been mass labeled with heavy isotopes [Boisvert, F.
      M., Lam, Y. W., Lamont, D., Lamond, A. I., Mol. Cell. Proteomics 2010, 9, 457
      470]. This was used here to measure the relative distribution between cytoplasm,
      nucleus and nucleolus of around 2000 proteins in HCT116 cells that are either
      expressing wild-type p53 or null for p53. Spatial proteomics also facilitates a
      proteome-wide comparison of changes in protein localization in response to a wide
      range of physiological and experimental perturbations. We used this method to
      study differences in protein localization in HCT116 cells either with or without
      p53, and studied the differences in cellular response to DNA damage following
      treatment of HCT116 cells with etoposide in both p53 wild-type and null genetic
      backgrounds.

PMID- 21080494
TI  - Molecular characterization of the endoplasmic reticulum: insights from proteomic
      studies.
AB  - The endoplasmic reticulum (ER) is a multifunctional intracellular organelle
      responsible for the synthesis, processing and trafficking of a wide variety of
      proteins essential for cell growth and survival. Therefore, comprehensive
      characterization of the ER proteome is of great importance to the understanding
      of its functions and has been actively pursued in the past decade by scientists
      in the proteomics field. This review summarizes major proteomic studies published
      in the past decade that focused on the ER proteome. We evaluate the data sets
      obtained from two different organs, liver and pancreas each of which contains a
      primary cell type (hepatocyte and acinar cell) with specialized functions. We
      also discuss how the nature of the proteins uncovered is related to the methods
      of organelle purification, organelle purity and the techniques used for protein
      separation prior to MS. In addition, this review also puts emphasis on the
      biological insights gained from these studies regarding the molecular functions
      of the ER including protein synthesis and translocation, protein folding and
      quality control, ER-associated degradation and ER stress, ER export and membrane
      trafficking, calcium homeostasis and detoxification and drug metabolism.

PMID- 21080497
TI  - Proteomic analysis of endosomes from genetically modified p14/MP1 mouse embryonic
      fibroblasts.
AB  - The p14/MP1 scaffold complex binds MEK1 and ERK1/2 on late endosomes, thus
      regulating the strength, duration and intracellular location of MAPK signaling.
      By organelle proteomics we have compared the protein composition of endosomes
      purified from genetically modified p14-/-, p14+/- and p14(rev) mouse embryonic
      fibroblasts. The latter ones were reconstituted retrovirally from p14-/- mouse
      embryonic fibroblasts by reexpression of pEGFP-p14 at equimolar ratios with its
      physiological binding partner MP1, as shown here by absolute quantification of
      MP1 and p14 proteins on endosomes by quantitative MS using the Equimolarity
      through Equalizer Peptide strategy. A combination of subcellular fractionation, 2
      D DIGE and MALDI-TOF/TOF MS revealed 31 proteins differentially regulated in p14
      /- organelles, which were rescued by reexpression of pEGFP-p14 in p14-/-
      endosomes. Regulated proteins are known to be involved in actin remodeling,
      endosomal signal transduction and trafficking. Identified proteins and their in
      silico interaction networks suggested that endosomal signaling might regulate
      such major cellular functions such as proliferation, differentiation, migration
      and survival.

PMID- 21080496
TI  - Analysis of phagosomal proteomes: from latex-bead to bacterial phagosomes.
AB  - Phagosomal proteome characterization has contributed significantly to the
      understanding of host-pathogen interaction and the mechanism of infectious
      diseases caused by intracellular bacteria. The latex bead-containing phagosome
      has been widely used as a model system to study phagosomal proteomes at a global
      level. In contrast, the study of bacteria-containing phagosomes at a similar
      level has just begun. A number of intracellular microbial species are studied for
      their proteomes during the invasion of a host, providing insight into their
      metabolic adaptation in host cells and interaction with host-cell antimicrobial
      environments. In this review, we attempt to summarize the most recent
      advancements in the proteomic study of microbial phagosomes, especially those
      originating from mouse or human cells. We also briefly describe the proteomics of
      latex bead-containing phagosomes because they are often used as model phagosomes
      for study. We provide descriptions on major biological and technological
      components in phagosomal proteome studies. We also discuss the role of phagosomal
      proteome study in the broader horizon of systems biology and the technological
      challenges in phagosomal proteome characterization.

PMID- 21080500
TI  - Evaluation of the LTQ-Orbitrap mass spectrometer for the analysis of polymerase
      chain reaction products.
AB  - We have investigated the potential and robustness of the off-line coupling of
      polymerase chain reaction (PCR) with electrospray ionization mass spectrometry
      (ESI-MS), for further applications in the screening of single-nucleotide
      polymorphisms (SNPs). This was based on recently reported data demonstrating that
      anion-exchange solid-phase extraction was the most efficient technique for
      efficiently desalting PCR products, with a recovery of ~70%. Results showed that
      this purification approach efficiently removes almost all the chemicals commonly
      added to PCR buffers. ESI-MS analysis of a model 114-bp PCR product performed on
      the LTQ-Orbitrap instrument demonstrated that detection limits in the nM range
      along with an average mass measurement uncertainty of 9.15 +/- 7.11 ppm can be
      routinely obtained using an external calibration. The PCR/ESI-MS platform was
      able to detect just a few copies of a targeted oligonucleotide. However, it was
      shown that if two PCR products are present in a mixture in a ratio higher than 10
      to 1, the lower abundance one might not be reproducibly detected. Applications to
      SNPs demonstrated that an LTQ-Orbitrap with a resolution of 30 000 (at m/z 400)
      easily identified a single (A <-> G) switch, i.e. a 16 Da difference, in binary
      mixtures of ~ 35 kDa PCR products. Complementary experiments also showed that the
      combination of endonucleases and ESI-MS could be used to confirm base composition
      and sequence, and thus to screen for unknown polymorphisms in specific sequences.
      For example, a single (T <-> A) switch (9 Da mass difference) was successfully
      identified in a 114-bp PCR product.

PMID- 21080501
TI  - Effect of solvent and electrospray mass spectrometer parameters on the charge
      state distribution of peptides--a case study using liquid chromatography/mass
      spectrometry method development for beta-endorphin assay.
AB  - Beta-endorphin was used as a model peptide to study the effect of solvent and
      electrospray mass spectrometer parameters in the optimisation of an assay method
      for multiply charged compounds using liquid chromatography/mass spectrometry
      (LC/MS). Unlike with singly charged compounds, the charge state distribution has
      a significant impact in the method development of multiply charged compounds such
      as peptides. Using a 50% acetonitrile/water solvent mixture, we found that the
      ion spray voltage had no influence on the charge state distribution. However,
      increasing declustering potential led to deprotonation of the higher charge
      states of the peptide thus causing a shift to lower charge states. The mechanism
      leading to the deprotonation was examined. It was concluded that the
      deprotonation is due to endoergic proton transfer from the peptide to solvent
      molecules clustered to the peptide that occurs in the declustering region. The
      extent of deprotonation increases with increasing proton affinity of the
      molecules of the non-aqueous solvent component used. Thus, if desired,
      deprotonation can be avoided by selecting a low proton affinity solvent such as
      methanol. The focusing potential was also found to have a great influence on the
      charge state distribution observed. The results of this study enabled us to
      select the optimum ion to be used in single ion/reaction monitoring mode. They
      also provided the most favourable parameter values to be used in the method to
      obtain the best sensitivity for the ion of choice. The results demonstrate the
      importance of considering the charge state distribution in the optimisation of
      electrospray LC/MS methods for multiply charged compounds.

PMID- 21080502
TI  - Diet discrimination factors are inversely related to delta15 N and delta13C
      values of food for fish under controlled conditions.
AB  - A recent literature review reported negative relationships between diet
      discrimination factors (DDFs = X(fish) - X(food) ; X = delta(15) N or delta(13)
      C) and the values of delta(15) N and delta(13) C in the food of wild organisms
      but there has been no laboratory-based confirmation of these relationships to
      date. Laboratory reared guppies (Poecilia reticulata) fed a series of diets with
      a range of delta(13) C (-22.9 to -6.60/00) and delta(15) N (6.5 to 15860/00)
      values were used to magnify diet-tissue dynamics in order to calculate DDFs once
      the fish had achieved equilibrium with each of the diets. Values of DDFs range
      widely for delta(15) N (7.1 to -8490/00) and delta(13) C (1.1 to -7.00/00) and
      showed a strong negative correlation with the stable isotope value in the food
      for delta(15) N (slope = -0.59 +/- 0.02, r(2)  = 0.95) and delta(13) C (slope = 
      0.56 +/- 0.02, r(2)  = 0.94). Based on these relationships, the magnitude of DDF
      change over environmentally relevant values of delta(15) N or delta(13) C would
      be significant and could confound the interpretation of stable isotopes in the
      environment. Using highly enriched experimental diets, our study adds to a
      growing number of studies that undermine the consistent trophic enrichment
      paradigm with results that demonstrate the currently poor mechanistic
      understanding of how DDFs arise. The results of our study highlight that the
      magnitude of the stable isotope values in prey must be considered when choosing
      DDF values. Future laboratory studies should therefore be directed at uncovering
      the mechanistic basis of DDFs and, like others before, we recommend the
      determination of diet-dependent DDFs under laboratory conditions before modeling
      dietary proportions or calculating trophic positions.

PMID- 21080498
TI  - The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein
      machine.
AB  - Almost all primary transcripts in higher eukaryotes undergo several splicing
      events and alternative splicing is a major factor in generating proteomic
      diversity. Thus, the spliceosome, the ribonucleoprotein assembly that performs
      splicing, is a highly critical cellular machine and as expected, a very complex
      one. Indeed, the spliceosome is one of the largest, if not the largest, molecular
      machine in the cell with over 150 different components in human. A large fraction
      of the spliceosomal proteome is organized into small nuclear ribonucleoprotein
      particles by associating with one of the small nuclear RNAs, and the function of
      many spliceosomal proteins revolve around their association or interaction with
      the spliceosomal RNAs or the substrate pre-messenger RNAs. In addition to the
      complex web of protein-RNA interactions, an equally complex network of protein
      protein interactions exists in the spliceosome, which includes a number of large,
      conserved proteins with critical functions in the spliceosomal catalytic core.
      These include the largest conserved nuclear protein, Prp8, which plays a critical
      role in spliceosomal function in a hitherto unknown manner. Taken together, the
      large spliceosomal proteome and its dynamic nature has made it a highly
      challenging system to study, and at the same time, provides an exciting example
      of the evolution of a proteome around a backbone of primordial RNAs likely dating
      from the RNA World.

PMID- 21080503
TI  - Empirical equations for the temperature dependence of calcite-water oxygen
      isotope fractionation from 10 to 70 degrees C.
AB  - Although the temperature dependence of calcite-water oxygen isotope fractionation
      seems to have been well established by numerous empirical, experimental and
      theoretical studies, it is still being discussed, especially due to the demand
      for increased accuracy of paleotemperature calculations. Experimentally
      determined equations are available and have been verified by theoretical
      calculations (considered as representative of isotopic equilibrium); however,
      many natural formations do not seem to follow these relationships implying either
      that existing fractionation equations should be revised, or that carbonate
      deposits are seriously affected by kinetic and solution chemistry effects, or
      late-stage alterations. In order to test if existing fractionation-temperature
      relationships can be used for natural deposits, we have studied calcite
      formations precipitated in various environments by means of stable isotope mass
      spectrometry: travertines (freshwater limestones) precipitating from hot and warm
      waters in open-air or quasi-closed environments, as well as cave deposits formed
      in closed systems. Physical and chemical parameters as well as oxygen isotope
      composition of water were monitored for all the investigated sites. Measuring
      precipitation temperatures along with oxygen isotope compositions of waters and
      calcites yielded empirical environment-specific fractionation-temperature
      equations: [1] 1000 . lnalpha = 17599/T - 29.64 [for travertines with a
      temperature range of 30 to 70 degrees C] and [2] 1000 . lnalpha = 17500/T - 29.89
      [for cave deposits for the range 10 to 25 degrees C]. Finally, based on the
      comparison of literature data and our results, the use of distinct calcite-water
      oxygen isotopic fractionation relationships and application strategies to obtain
      the most reliable paleoclimate information are evaluated.

PMID- 21080504
TI  - Using a dual inlet atmospheric pressure ionization source as a dynamic reaction
      vessel.
AB  - Atmospheric pressure ionization (API) sources have the ability to serve as
      dynamic 'reaction vessels' and this capability has been rapidly evolving over the
      past few years. With API sources, many different reagents and source conditions
      can be rapidly explored with minimal carryover or contamination of the mass
      spectrometer. While most API applications involve the simple
      protonation/deprotonation of analyte molecules, a great deal of flexibility and
      utility is available in almost any API source, provided the reagents and
      ionization conditions are judiciously selected. Here, the generation of a unique
      and useful class of reagent ions at atmospheric pressure is demonstrated for the
      first time. Within the AP gas-phase environment of a dual inlet ion source, the
      gas-phase synthesis of substituted N-phenylpyridinium cations is demonstrated by
      establishing conditions favorable to the nucleophilic substitution reaction
      required for their formation. The flexibility of this API source as a reaction
      vessel is also demonstrated.

PMID- 21080505
TI  - Determination of polymer electrolyte membrane (PEM) degradation products in fuel
      cell water using electrospray ionization tandem mass spectrometry.
AB  - Within the scope of research of membrane degradation phenomena during fuel cell
      operation a reliable analytical procedure for the extraction, detection and
      quantification of possible membrane oxidation products has been developed. These
      oxidation products originate from the attack of hydroxyl or peroxyl radicals on
      the membrane polymer. Such radicals are formed in situ (during fuel cell
      operation) or ex situ (Fenton test as oxidative stress simulation). The analysis
      of membrane oxidation products was carried out by electrospray ionization tandem
      mass spectrometry. Five potential membrane oxidation products (4-hydroxybenzoic
      acid (4-HBA), 4-hydroxybenzaldehyde (4-HBAD), 4,4-biphenol (4,4-BP), 4
      hydroxybenzenesulfonate (4-HBS), and 4,4-sulfonylbiphenol (4,4-SBP)) were
      selected based on the molecular structure of the sulfonated polyarylether
      membrane used. In conjunction with the development of a multiple reaction
      monitoring (MRM) method, the ionization and fragmentation of the selected
      compounds were investigated. For 4,4-BP a molecular ion (M(+*) ) was observed in
      the positive ionization mode and used for MRM method development. Reproducible
      extraction of the model compounds was achieved using a mixed-mode sorbent
      material with both weak anion-exchange and reversed-phase retention properties.
      By using the developed analytical procedure, the identities of two membrane
      degradation products (4-HBA and 4-HBAD) were determined in situ and ex situ. In
      addition to the investigation of membrane degradation phenomena, the combination
      of extraction on a mixed-mode sorbent material and tandem mass spectrometric
      detection is attractive for the analysis of aromatic sulfonic acids, phenolic
      acids and phenols.

PMID- 21080506
TI  - Study of plasma metabolic profiling and biomarkers of chronic unpredictable mild
      stress rats based on gas chromatography/mass spectrometry.
AB  - A metabolomic investigation of chronic unpredictable mild stress (CUMS) rats was
      carried out. Plasma obtained from Sprague-Dawley (SD) rats treated by CUMS was
      analyzed using gas chromatography/mass spectrometry. Thirty-seven metabolites
      were identified among the detected compounds. Subsequent data analysis using the
      t test and principal component analysis (PCA) revealed significant metabolic
      changes in the rats' plasma after CUMS treatment. Clear separation between the
      model and control group was achieved, and the level of twelve metabolites,
      including amino acids, sugar, organic acids and fatty acids, were significantly
      different between plasma samples from the controls and CUMS group. These
      observations suggested that the depressed state may be associated with
      perturbation of amino acid metabolism, energy metabolism and glycometabolism. The
      study suggested that the metabolomics approach could be used as a potential
      powerful tool to investigate the biochemical change in certain physiopathological
      conditions, such as depression, as an early diagnostic means.

PMID- 21080508
TI  - Concentration effects on laser-based delta18 O and delta2 H measurements and
      implications for the calibration of vapour measurements with liquid standards.
AB  - Recently available isotope ratio infrared spectroscopy can directly measure the
      isotopic composition of atmospheric water vapour (delta(18) O, delta(2) H),
      overcoming one of the main limitations of isotope ratio mass spectrometry (IRMS)
      methods. Calibrating these gas-phase instruments requires the vapourisation of
      liquid standards since primary standards in principle are liquids. Here we test
      the viability of calibrating a wavelength-scanned cavity ring-down spectroscopy
      (CRDS) instrument with vapourised liquid standards. We also quantify the
      dependency of the measured isotope values on the water concentration for a range
      of isotopic compositions. In both liquid and vapour samples, we found an increase
      in delta(18) O and delta(2) H with water vapour concentration. For delta(18) O,
      the slope of this increase was similar for liquid and vapour, with a slight
      positive relationship with sample delta-value. For delta(2) H, we found diverging
      patterns for liquid and vapour samples, with no dependence on delta-value for
      vapour, but a decreasing slope for liquid samples. We also quantified tubing
      memory effects to step changes in isotopic composition, avoiding concurrent
      changes in the water vapour concentration. Dekabon tubing exhibited much
      stronger, concentration-dependent, memory effects for delta(2) H than stainless
      steel or perfluoroalkoxy (PFA) tubing. Direct vapour measurements with CRDS in a
      controlled experimental chamber agreed well with results obtained from vapour
      simultaneously collected in cold traps analysed by CRDS and IRMS. We conclude
      that vapour measurements can be calibrated reliably with liquid standards. We
      demonstrate how to take the concentration dependencies of the delta-values into
      account. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID- 21080507
TI  - Synthesis, characterization and application of modified Pd nanoparticles as
      preconcentration probes for selective enrichment/analysis of proteins via
      hydrophobic interactions from real-world samples using nanoparticle-liquid-liquid
      microextraction coupled to matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry.
AB  - We introduce a novel preconcentrating technique by using surface modification of
      palladium nanoparticles (Pd-NPs) with octadecane thiol (ODT) prepared in toluene
      for selective and sensitive extraction of proteins (insulin, ubiquitin, lysozyme)
      from a variety of real-world samples including pancreas, mushroom, soybean and
      milk using nanoparticle-liquid-liquid microextraction (NP-LLME) coupled to matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS).
      The limit of detection (LOD) values obtained for gramicidin D and insulin in
      water and urine are between 17-37 nM (17-37 fmol) (with RSDs ranging from 5.3
      7.2%) which are 10-20-fold enhancement in detection sensitivity compared with
      conventional MALDI-MS. The optimal sample pH for highest extraction efficiency of
      insulin, ubiquitin and lysozyme from biological samples was observed at sample pH
      ~ pI which could be due to the enhancement of hydrophobic interactions between
      proteins with the hydrophobic ligands of Pd-ODT NPs. In addition, we also found
      that with the addition of 1 M NaCl, signals could be significantly enhanced by
      using the current approach. It is an efficient, straightforward, sensitive and
      selective nanoprobe which can be widely applied for separation, enrichment and
      preconcentration of peptides or proteins from complex biological samples in
      proteome research.

PMID- 21080509
TI  - Characterization of [peptide+(Ag)n]+ complexes using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Silver ion complexes of peptides [M + (Ag)(n) ](+) , M = angiotensin I or
      substance P where n = 1-8 and 17-23 for angiotensin I and n = 1-5 for substance
      P, are identified and characterized using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The Ag(+)
      coordination number exceeds the number of available amino acid residues in
      angiotensin I whereas the number of observed complexes in substance P is less
      than the number of amino acid residues in it. The larger coordination number of
      angiotensin I with Ag(+) indicates the simultaneous binding of several Ag(+) ions
      to the amino acid residue present in it. The lower number of observed complexes
      in substance P suggests the binding of two or more residues to one Ag(+) ion. The
      presence of trifluoroacetic acid in the peptide samples reduces the Ag(+)
      coordination ability in both the peptides which indicates that the basic residues
      in it are already protonated and do not participate in the Ag(+) -binding
      process. The Ag(+) ion also forms a complex with the alpha-cyano-4
      hydroxycinnamic acid (CHCA) matrix and is observed in the MALDI mass spectra and
      the formation of [CHCA + Ag](+) , [CHCA + AgNO(3) ](+) and [(CHCA)(2)  + Ag](+)
      ions is due to the high binding affinity of Ag(+) to the CN group of CHCA.

PMID- 21080511
TI  - An integrated bioanalytical platform for supporting high-throughput serum protein
      binding screening.
AB  - Quantification of small molecules using liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) on a triple quadrupole mass spectrometer has become a
      common practice in bioanalytical support of in vitro adsorption, distribution,
      metabolism and excretion (ADME) screening. The bioanalysis process involves
      primarily three indispensable steps: MS/MS optimization for a large number of new
      chemical compounds undergoing various screening assays in early drug discovery,
      high-throughput sample analysis with LC/MS/MS for those chemically diverse
      compounds using the optimized MS/MS conditions, and post-acquisition data review
      and reporting. To improve overall efficiency of ADME bioanalysis, an integrated
      system was proposed featuring an automated and unattended MS/MS optimization, a
      staggered parallel LC/MS/MS for high-throughput sample analysis, and a
      sophisticated software tool for LC/MS/MS raw data review as well as biological
      data calculation and reporting. The integrated platform has been used in
      bioanalytical support of a serum protein binding screening assay with high speed,
      high capacity, and good robustness. In this new platform, a unique sample
      dilution scheme was also introduced. With this dilution design, the total number
      of analytical samples was reduced; therefore, the total operation time was
      reduced and the overall throughput was further improved. The performance of the
      protein binding screening assay was monitored with two controls representing high
      and low binding properties and an acceptable inter-assay consistency was
      achieved. This platform has been successfully used for the determination of serum
      protein binding in multiple species for more than 4000 compounds.

PMID- 21080510
TI  - Bioassay-directed fractionation for discovery of bioactive neutral lipids guided
      by relative mass defect filtering and multiplexed collision-induced dissociation.
AB  - We report a synergistic method using bioassay-directed liquid chromatography
      fractionation and time-of-flight mass spectrometry to guide and accelerate
      bioactive compound discovery. To steer purification and assays toward anticipated
      neutral lipid activators of a constitutive androstane receptor splice variant, a
      relative mass defect filter was calculated, based on the ratio of the mass defect
      to the measured ion mass, and used to reduce the number of candidate ion masses.
      Mass measurements often lack sufficient accuracy to provide unambiguous
      assignments of elemental compositions, and since the relative mass defect
      reflects fractional hydrogen content of ions, this value is largely determined by
      the hydrogen content of a compound's biosynthetic precursors. A relative mass
      defect window ranging from 600-1000 ppm, consistent with an assortment of lipids,
      was chosen to assess the number of candidate ions in fractions of fetal bovine
      serum. This filter reduced the number of candidate ion m/z values from 1345 to
      892, which was further reduced to 21 by intensity and isotope filtering. Accurate
      mass measurements from time-of-flight mass spectrometry and fragment ion masses
      generated using nonselective collision-induced dissociation suggested dioctyl
      phthalate as one of few neutral lipid constituents in the active fraction. The
      identity of this compound was determined to be di(2-ethylhexyl) phthalate using
      GC/MS, and it was ranked as a promising candidate for reporter assay screening.

PMID- 21080512
TI  - Structural study of acetogenins by tandem mass spectrometry under high and low
      collision energy.
AB  - Collision-induced dissociation experiments of seven annonaceous acetogenins were
      carried out under high and low collision energy conditions. Each compound was
      studied as protonated or deprotonated and lithium- or sodium- cationized
      molecules, using ElectroSpray Ionisation (ESI) with a hybrid linear trap/orbitrap
      mass spectrometer (LTQ-Orbitrap(r)). The same ion species were studied with a
      Matrix-Assisted Laser Desorption Ionisation (MALDI) tandem mass spectrometer in a
      high collision energy regime (1 or 2 keV). Although each of the techniques showed
      some limitations in the detection of functional groups, unambiguous structural
      identification of the acetogenins was obtained. MALDI ToF-ToF has the advantage
      over ESI-based methods to provide mass spectra rich in informative fragments
      which allows the confirmation of some functional groups position. By contrast,
      ESI-LTQ-Orbitrap(r) analysis has the advantage over MALDI that the mass spectra
      are relatively simple with only fragments close to the functional groups.
      However, this technique needs to carry out experiments both in negative and
      positive ionization modes. Copyri

PMID- 21080513
TI  - A suite of sensitive chemical methods to determine the delta15N of ammonium,
      nitrate and total dissolved N in soil extracts.
AB  - Natural (15) N abundances (delta(15) N values) of different soil nitrogen pools
      deliver crucial information on the soil N cycle for the analysis of
      biogeochemical processes. Here we report on a complete suite of methods for
      sensitive delta(15) N analysis in soil extracts. A combined chemical reaction of
      vanadium(III) chloride (VCl(3) ) and sodium azide under acidic conditions is used
      to convert nitrate into N(2) O, which is subsequently analyzed by purge-and-trap
      isotope ratio mass spectrometry (PTIRMS) with a cryo-focusing unit. Coupled with
      preparation steps (microdiffusion for collection of ammonium, alkaline persulfate
      oxidation to convert total dissolved N (TDN) or ammonium into nitrate) this
      allows the determination of the delta(15) N values of nitrate, ammonium and total
      dissolved N (dissolved organic N, microbial biomass N) in soil extracts with the
      same basic protocol. The limits of quantification for delta(15) N analysis with a
      precision of 0.50/00 were 12.4 uM for ammonium, 23.7 uM for TDN, 16.5 uM for
      nitrate and 22.7 uM for nitrite.

PMID- 21080516
TI  - Optical bioimaging and neuroimaging: from whole-body inspection to brain sensing.

PMID- 21080518
TI  - [Proceedings from the Endocrine Society Meeting 2009 and review of the
      Neuroendocrinology Group of the SEEN].

PMID- 21080519
TI  - Alemtuzumab treatment for hemophagocytic lymphohistiocytosis.

PMID- 21080520
TI  - [Dynamics of benthic communities in the central trench of the Barents Sea].
AB  - Based on the data collected in five marine expeditions of the Murmansk Marine
      Biological Institute from 2002 through 2007, the spatial and temporary
      variability of benthic communities in the Central Depression of the Barents Sea
      (licensed plot of the Shtokmanovskoe condensed gas deposit) has been analyzed.
      The range of quantitative characteristics and the variability of species
      composition of deep-water zoobenthos have been determined. The influence of an
      insignificant change in the collecting method on the obtained results has been
      examined.

PMID- 21080521
TI  - [Molluscum contagiosum].

PMID- 21080523
TI  - ESC recommendations for individual certification and institutional cardiovascular
      magnetic resonance accreditation, in Europe.

PMID- 21080522
TI  - [Colleague internet: experience interchange in medical communities].

PMID- 21080524
TI  - There are two different career tracks for academic medicine in the USA.

PMID- 21080525
TI  - Genzyme's research in cardiovascular disease, putting rare conditions on centre
      stage.

PMID- 21080526
TI  - Towards individualized preventive therapy.

PMID- 21080527
TI  - Impact of transmitted drug-resistance on treatment selection and outcome of first
      line Highly Active Antiretroviral Therapy (HAART).
AB  - OBJECTIVE: The study aim was to determine how resistance testing influences
      outcome of first-line highly active antiretroviral therapy (HAART) in routine
      practice in the United Kingdom. METHODS: The prevalence of transmitted drug
      resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens
      were determined using data from the UK Collaborative HIV Cohort(CHIC) Study.
      Factors associated with starting a regimen with a reduced GSS and subsequent
      virological responses were analyzed by logistic and Cox regression. RESULTS:
      Amongst patients tested in 1999-2006, 116 of 1175 (10%) had $1 resistance
      mutation; 64 patients (5.4%) had $1 mutation associated with resistance to drugs
      in the initial HAART regimen and 54 (4.6%) showed a GSS, 3. Factors independently
      associated with a GSS, 3 were starting HAART in 1999-2001 vs. 2004-2006 (odds
      ratio = 2.63; 95% confidence interval: 1.19 to 5.83) and use of ritonavir-boosted
      protease inhibitor (PI/r)-based vs. nonnucleoside reverse transcriptase inhibitor
      based regimens (1.97; 1.06 to 3.64). AGSS .3 was independently associated with
      virological suppression(hazard ratio for GSS, 3 = 0.60; 95% confidence interval
      0.41 to 0.87). CONCLUSIONS: Most patients starting HAART after undergoing
      resistance testing received regimens with a GSS $3. PI/r-based therapy was often
      selected in patients with resistance to the nucleoside reverse transcriptase
      inhibitor backbone. Low GSS predicted poor virological suppression and the
      association persisted after adjusting for PI/r use.

PMID- 21080528
TI  - Metabolism: An appetite for exercise.

PMID- 21080529
TI  - Receptor physiology: It's the NMDA receptor, but not as we know it.

PMID- 21080530
TI  - Neuroimmunology: Working memory takes its toll.

PMID- 21080531
TI  - Synaptic transmission: A closer look at presynaptic GABA(B) receptors.

PMID- 21080532
TI  - Proprioception: Sensational mechanics.

PMID- 21080533
TI  - Psychiatric disorders: Ketamine modifies mood through mTOR.

PMID- 21080535
TI  - Neurodegenerative disease: New leads for Parkinson's disease.

PMID- 21080534
TI  - Diabetes: Dapagliflozin: an insulin-independent, therapeutic option for type 2
      diabetes mellitus.

PMID- 21080536
TI  - Cancer: Bisphosphonate use and breast cancer.

PMID- 21080537
TI  - Neuron-glia interactions: Parting the waves.

PMID- 21080538
TI  - Addiction: Cracking the code of addiction.

PMID- 21080539
TI  - Nutrition: Vitamin D improves blood pressure in type 2 diabetes.

PMID- 21080540
TI  - An interview with the Kavli prize winners. Interview by Claudia Wiedemann.

PMID- 21080541
TI  - Celiac disease: Diet and BMD loss.

PMID- 21080543
TI  - A Nobel endeavour.

PMID- 21080542
TI  - Surgery: Laparoscopic sleeve gastrectomy as the first-line surgical option for
      morbid obesity.

PMID- 21080544
TI  - Screening: Sensitivity versus specificity: neonatal screening for congenital
      hypothyroidism.

PMID- 21080545
TI  - Bacterial lipid rafts discovered.

PMID- 21080546
TI  - Bone: Promising combination therapy for children with osteogenesis imperfecta.

PMID- 21080547
TI  - Eptifibatide is noninferior to abciximab:  implications for clinical practice.

PMID- 21080548
TI  - Cancer: Well-differentiated thyroid cancer: 124I PET superior to 131I planar
      imaging.

PMID- 21080549
TI  - Severing the bud.

PMID- 21080550
TI  - Polymorphism affects GH therapy.

PMID- 21080551
TI  - Raised blood-pressure measurements  are under-recognized in children.

PMID- 21080552
TI  - Diabetes: Environmental influence on diabetes prevalence.

PMID- 21080553
TI  - Air pollution  reduces EPC levels.

PMID- 21080554
TI  - Greasing the wheels of replication.

PMID- 21080555
TI  - Off-target effects  of torcetrapib.

PMID- 21080556
TI  - Automatic remote home monitoring  is a safe option for ICD follow-up.

PMID- 21080557
TI  - Wearable cardioverter-defibrillators  in the spotlight.

PMID- 21080558
TI  - Assessment of extended-duration  enoxaparin for VTE.

PMID- 21080559
TI  - New CMR approach to measure diffuse myocardial fibrosis.

PMID- 21080560
TI  - Gaining an edge in the gut.

PMID- 21080561
TI  - A helping hand.

PMID- 21080562
TI  - Tumour progression: Disease connections.

PMID- 21080564
TI  - Therapy: Good old herbs.

PMID- 21080563
TI  - Cancer viruses: a two-pronged attack.

PMID- 21080565
TI  - Tumorigenesis: Dangerous micromanagement.

PMID- 21080566
TI  - Hydrothermal growth mechanism of alpha-Fe2O3 nanorods derived by near in situ
      analysis.
AB  - The hydrothermal growth mechanism of alpha-Fe2O3 nanorods has been investigated
      using a novel valve assisted pressure autoclave. This approach has facilitated
      the rapid quenching of hydrothermal suspensions into liquid nitrogen, providing
      'snapshots' representative of the near in situ physical state of the synthesis
      reaction products as a function of known temperature. Examination of the acquired
      samples using complementary characterisation techniques of transmission electron
      microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared
      spectroscopy (FT-IR) has provided fundamental insight into the anisotropic
      crystal growth mechanism of the lenticular alpha-Fe2O3 nanorods.An intermediate
      beta-FeOOH phase was observed to precipitate alongside small primary alpha-Fe2O3
      nanoparticles. Dissolution of the beta-FeOOH phase with increasing temperature,
      in accordance with Ostwald's rule of stages, led to the release of Fe3+ anions
      back into solution to supply the growth of alpha-Fe2O3 nanoparticles, which in
      turn coalesced to form lenticular alpha-Fe2O3 nanorods. The critical role of the
      PO43- surfactant on mediating the lenticular shape of the alpha-Fe2O3 nanorods is
      emphasised. Strong phosphate anion absorption on alpha-Fe2O3 crystal surfaces
      stabilised the primary alpha-Fe2O3 nanoparticle size to < 10 nm. FT-IR
      investigation of the quenched reaction products provided evidence for PO43-
      absorption on the alpha-Fe2O3 nanoparticles in the form of mono or bi-dentate
      (bridging) surface complexes on surfaces normal and parallel to the
      crystallographic alpha-Fe2O3 c-axis, respectively. Monodentate PO43- absorption
      is considered weaker and hence easily displaced during growth, as compared to
      absorbed PO43- bi-dentate species, which implies the alpha-Fe2O3 c-planes are
      favoured for the oriented attachment of primary alpha-Fe2O3 nanoparticles,
      resulting in the development of filamentary features which act as the basis of
      growth, defining the shape of the lenticular alpha-Fe2O3 nanorods.

PMID- 21080567
TI  - Tumorigenesis: Merlin, the liver wizard.

PMID- 21080569
TI  - Immunotherapy: Enlisting the enemy.

PMID- 21080568
TI  - Metastasis: Twisting BMI1.

PMID- 21080570
TI  - Mesoscale crystallization of calcium phosphate nanostructures in protein (casein)
      micelles.
AB  - Aqueous micelles of the multi-protein calcium phosphate complex, casein, were
      treated at 60 degrees C and pH 7 over several months. Although partial
      dissociation of the micelles into 12 nm sized amorphous calcium phosphate
      (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization
      of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was
      not observed until after 12 weeks. The HAP nanofilaments were formed specifically
      within the partially disrupted protein micelles suggesting a micelle-mediated
      pathway of mesoscale crystallization. Similar experiments using ACP-containing
      synthetic micelles prepared from beta-casein protein alone indicated that co
      aligned bundles of HAP nanofilaments were produced within the protein micelle
      interior after 24 hours at temperatures as low as 35 degrees C. The presence of
      Mg2(+) ions in the casein micelles, as well as a possible synergistic effect
      associated with the multi-protein nature of the native aggregates, could account
      for the marked inhibition in mesoscale crystallization observed in the casein
      micelles compared with the single-component b-casein constructs.

PMID- 21080571
TI  - Epitaxial overgrowth of platinum on palladium nanocrystals.
AB  - This paper describes a systematic study on the epitaxial overgrowth of Pt on well
      defined Pd nanocrystals with different shapes (and exposed facets), including
      regular octahedrons, truncated octahedrons, and cubes. Two different reducing
      agents, i.e., citric acid and L-ascorbic acid, were evaluated and compared for
      the reduction of K2PtCl4 in an aqueous solution in the presence of Pd nanocrystal
      seeds. When citric acid was used as a reducing agent, conformal overgrowth of
      octahedral Pt shells on regular and truncated octahedrons of Pd led to the
      formation of Pd-Pt core-shell octahedrons, while non-conformal overgrowth of Pt
      on cubic Pd seeds resulted in the formation of an incomplete octahedral Pt shell.
      On the contrary, localized overgrowth of Pt branches was observed when L-ascorbic
      acid was used as a reducing agent regardless of the facets expressed on the
      surface of Pd nanocrystal seeds. This work shows that both the binding affinity
      of a reducing agent to the Pt surface and the reduction kinetics for a Pt
      precursor play important roles in determining the mode of Pt overgrowth on Pd
      nanocrystal surface.

PMID- 21080572
TI  - Can exercise advice be 'made to stick'? Combining psychology and technology to
      improve patient uptake of physical activity prescription.

PMID- 21080573
TI  - Should sinus rhythm be restored in patients with AF and HF?

PMID- 21080574
TI  - Interventional cardiology: TAVI is effective for the treatment of high-risk
      patients.

PMID- 21080575
TI  - Add-on treprostinil therapy and PAH.

PMID- 21080576
TI  - Neutrophils stem the flow.

PMID- 21080577
TI  - KLF2 keeps B cells in their place.

PMID- 21080578
TI  - Interferons promote artery lesions.

PMID- 21080579
TI  - Chromosomal instability: Coping with extra copies.

PMID- 21080580
TI  - Present and clear danger.

PMID- 21080581
TI  - Tumorigenesis: Joining the RANKs.

PMID- 21080582
TI  - Tumours support the T cell response.

PMID- 21080583
TI  - China: a life sciences giant.

PMID- 21080584
TI  - Signalling: the calcium connection.

PMID- 21080585
TI  - Tumour suppression: Ejector seat.

PMID- 21080586
TI  - Expanding horizons through  chromosome exchange.

PMID- 21080587
TI  - NKT cells favour the unconventional.

PMID- 21080588
TI  - Epigenetics: Demethylation links cell fate and cancer.

PMID- 21080589
TI  - Ticked off basophils end banquet.

PMID- 21080590
TI  - Modifying virulent behaviour.

PMID- 21080591
TI  - Metabolism: Less is sometimes more.

PMID- 21080592
TI  - Sedentary versus inactive: distinctions for disease prevention.

PMID- 21080593
TI  - Real-time view of AMP-mediated killing.

PMID- 21080594
TI  - Immunology: In need of a boost?

PMID- 21080595
TI  - Helping plants to fight back.

PMID- 21080596
TI  - Stem cells: Out for the count.

PMID- 21080597
TI  - Pharmacogenetics: Clinical response to antiplatelet therapy--how much does
      genotype count?

PMID- 21080598
TI  - Collaborative control of induced regulators.

PMID- 21080599
TI  - Second hideout for HIV-1.

PMID- 21080600
TI  - Genetics: Partners in crime.

PMID- 21080601
TI  - The two faces of MycP1.

PMID- 21080602
TI  - Arrhythmias: Changes to recommendations for stroke prevention in AF.

PMID- 21080603
TI  - Prevention: Low-dose omega-3 supplementation--no beneficial effect in patients
      with prior MI.

PMID- 21080604
TI  - Acute coronary syndromes: A single dose of erythropoietin might improve outcomes
      after STEMI.

PMID- 21080605
TI  - Surgery: COPPS trial heralds new indication for colchicine.

PMID- 21080606
TI  - Prevention: Neuropsychiatric adverse effects signal the end of the line for
      rimonabant.

PMID- 21080608
TI  - Survival centre.

PMID- 21080607
TI  - Two for the price of one.

PMID- 21080609
TI  - Exhaustion through BATF.

PMID- 21080610
TI  - IAPP stokes the  pancreatic fire.

PMID- 21080611
TI  - A new vein of TLR biology.

PMID- 21080612
TI  - The T(H)17 kiss of death for neurons.

PMID- 21080613
TI  - Macrophages yo-yo during weight loss.

PMID- 21080614
TI  - Controlling neutrophil plasticity.

PMID- 21080615
TI  - One-two blow alerts  immune system.

PMID- 21080616
TI  - Extended cyclic fatigue life of F2 ProTaper instruments used in reciprocating
      movement.
AB  - AIM: To evaluate the cyclic fatigue fracture resistance of engine-driven F2
      ProTaper instruments under reciprocating movement. METHODOLOGY: A sample of 30
      NiTi ProTaper F2 instruments was used. An artificial canal was made from a
      stainless steel tube, allowing the instruments to rotate freely. During
      mechanical testing, different movement kinematics and speeds were used, which
      resulted in three experimental groups (n = 10). The instruments from the first
      group (G1) were rotated at a nominal speed of 250 rpm until fracture, whilst the
      instruments from the second group (G2) were rotated at 400 rpm. In the third
      instrument group (G3), the files were driven under reciprocating movement. The
      time of fracture for each instrument was measured, and statistical analysis was
      performed using parametric methods. RESULTS: Reciprocating movement resulted in a
      significantly longer cyclic fatigue life (P < 0.05). Moreover, operating rpm was
      a significant factor affecting cyclic fatigue life (P < 0.05); instruments used
      at a rotational speed of 400 rpm (approximately 95 s) failed more rapidly than
      those used at 250 rpm (approximately 25 s). CONCLUSIONS: Movement kinematics is
      amongst the factors determining the resistance of rotary NiTi instruments to
      cyclic fracture. Moreover, the reciprocating movement promoted an extended cyclic
      fatigue life of the F2 ProTaper instrument in comparison with conventional
      rotation.

PMID- 21080617
TI  - Laboratory diagnostics in the third millennium: where, how and why. Proceedings
      of a conference devoted to the memory of Professor Angelo Burlina. Padua, Italy.
      October 22, 2009.

PMID- 21080618
TI  - Primary congenital glaucoma associated with Patau syndrome with long survival.
AB  - Ocular abnormalities are common in Patau syndrome (trisomy 13), but only a few
      cases with congenital glaucoma have been reported, some of which were associated
      with other ocular defects. This report describes a case of primary congenital
      glaucoma in an 11-year-old patient with full trisomy 13.

PMID- 21080619
TI  - Understanding reaction mechanisms in organic chemistry from catastrophe theory:
      ozone addition on benzene.
AB  - The potential energy profiles of the endo and exo additions of ozone on benzene
      have been theoretically investigated within the framework provided by the
      electron localization function (ELF). This has been done by carrying out hybrid
      Hartree-Fock DFT B3LYP calculation followed by a bonding evolution theory (BET)
      analysis. For both approaches, the reaction is exothermic by ~98 kJ mol(-1).
      However, the activation energy is calculated to 10 kJ mol(-1) lower in the endo
      channel than in the exo one; therefore the formation of the endo C(6)H(6)O(3)
      adduct is kinetically favored. Six structural stability domains are identified
      along both reaction pathways as well as the bifurcation catastrophes responsible
      for the changes in the topology of the system. This provides a chemical
      description of the reaction mechanism in terms of heterolytic synchronous bond
      formation.

PMID- 21080620
TI  - Theoretical investigation on the isomerization reaction of 4-phenyl-hexa-1,5
      enyne catalyzed by homogeneous Au catalysts.
AB  - By carrying out density functional theory calculations, we have performed a
      detailed mechanism study for the cycloisomerization reaction of 4-phenyl-hexa-1,5
      enyne catalyzed by homogeneous gold to better understand the observed different
      catalytic activity of several catalysts, including (PPh(3))AuBF(4), (PPh(3))AuCl,
      AuCl(3), and AuCl. In all situations, the reaction is found to involve two major
      steps: the initial nucleophilic addition of the alkynyl onto the alkene group and
      the subsequent 1,2-H migration. It is found that the potential energy surface
      profiles of systems are very different when different catalysts are used. For
      (PMe(3))AuBF(4)- and (PMe(3))AuCl-mediated systems, the nucleophilic addition is
      the rate-determining step, and the calculated free energy barriers are 15.2 and
      41.9 kcal/mol, respectively. In contrast, for AuCl(3)- and AuCl-mediated systems,
      the reactions are controlled by the dissociations of catalysts from the product
      like intermediates, and the calculated dissociation energies are 18.1 and 21.7
      kcal/mol, respectively, which are larger than both the corresponding free energy
      barriers of the nucleophilic addition and the H-migration processes (8.5 and 7.3
      kcal/mol for the AuCl(3)-mediated reaction, and 16.9 and 11.3 kcal/mol for the
      AuCl-mediated reaction). These results can rationalize the early experimental
      observations that the reactant conversion rates are 100, 0, and 50% when using
      (PPh(3))AuBF(4), (PPh(3))AuCl, and AuCl(3) as catalysts, respectively. The
      present study indicates that both the ligand and counterion of homogeneous Au
      catalysts importantly influence their catalytic activities, whereas the oxidation
      state of Au is not a crucial factor controlling the reactivity.

PMID- 21080621
TI  - Crown ether complexes of HPCl6.
AB  - The reactions of HCl, PCl5, and a crown ether (12-crown-4 or 18-crown-6) in CHCl3
      under anaerobic conditions give complexes of the superacid HPCl6: [H(12-crown
      4)][PCl6 ] and [H(18-crown-6)2][PCl6]. The crystal structures indicate that the
      proton lies roughly in the center of the 12-crown-4 molecule in [H(12-crown
      4)][PCl6 ] whereas it lies between two oxygen atoms of two different 18-crown-6
      molecules in [H(18-crown-6)2][PCl6].

PMID- 21080622
TI  - Multiplexed and reiterative fluorescence labeling via DNA circuitry.
AB  - A class of reactive DNA circuits was adapted as erasable molecular imaging probes
      that allow fluorescent reporting complexes to be assembled and disassembled on a
      biological specimen. Circuit reactions are sequence-dependent and therefore
      facilitate multiplexed (multicolor) detection. Yet, the ability to disassemble
      reporting complexes also allows fluorophores to be removed and new circuit
      complexes to be used to label additional markers. Thus, these probes present
      opportunities to increase the total number of molecular targets that can be
      visualized on a biological sample by allowing multiple rounds of fluorescence
      microscopy to be performed.

PMID- 21080623
TI  - Chitosan-vancomysin composite biomaterial as a laser activated surgical adhesive
      with regional antimicrobial activity.
AB  - We have used laser irradiation to enhance the natural adhesiveness of chitosan to
      form a thin film surgical adhesive. Prevention of infection at surgical sites
      often utilizes systemic provision of antibiotics with reduced local efficacy and
      potential side effects. In the work reported here, we investigate the
      bactericidal properties of laser-irradiated chitosan films and their impregnation
      with the antibiotic vancomycin. Despite strong efficacy in solution, chitosan
      films showed no antimicrobial activity against representatives of common
      pathogens Escherichia coli , Staphylococcus aureus , and S. epidermidis . In
      contrast, a composite of chitosan adhesive and the antibiotic vancomycin showed
      therapeutically significant release profiles greater that the Minimum
      Bactericidal Concentrations (MBCs) for the Staphylococci over a 28 day period.
      These composite films had greater crystallinity, up to 28 +/- 3 compared to 8.9
      +/- 2%, for its unblended counterpart. Despite a significant increase in material
      strength from 31.4 +/- 4 to 77.5 +/- 5 MPa, flexibility was still maintained with
      an elongation to break around 5 +/- 2% and fold endurance of approximately 30 +/-
      3-folds. Laser irradiation had no apparent effect on the release or activity of
      the antibiotic which survived transient temperatures at the film-tissue interface
      during infrared irradiation of around 54  degrees C. Furthermore, significant
      adhesive strength was still apparent, 15.6 +/- 2 KPa. Thus, we have developed a
      laser-activated bioadhesive with the potential to close wounds while facilitating
      the prevention of microbial infection through local release of antibiotic
      targeted to the site of potential infection.

PMID- 21080624
TI  - Quantifying health improvements from water quantity enhancement: an engineering
      perspective applied to rainwater harvesting in West Africa.
AB  - Knowledge of potential benefits resulting from technological interventions
      informs decision making and planning of water, sanitation, and hygiene programs.
      The public health field has built a body of literature showing health benefits
      from improvements in water quality. However, the connection between improvements
      in water quantity and health is not well documented. Understanding the connection
      between technological interventions and water use provides insight into this
      problem. We present a model predicting reductions in diarrhea disease burden when
      the water demands from hygiene and sanitation improvements are met by domestic
      rainwater harvesting (DRWH). The model is applied in a case study of 37 West
      African cities. For all cities, with a total population of over 10 million, we
      estimate that DRWH with 400 L storage capacity could result in a 9% reduction in
      disability-affected life years (DALYs). If DRWH is combined with point of use
      (POU) treatment, this potential impact is nearly doubled, to a 16% reduction in
      DALYs. Seasonal variability of diarrheal incidence may have a small to moderate
      effect on the effectiveness of DRWH, depending on the storage volume used.
      Similar predictions could be made for other interventions that improve water
      quantity in other locations where disease burden from diarrhea is known.

PMID- 21080625
TI  - Rational design of responsive self-assembling peptides from native protein
      sequences.
AB  - This study used identified functional native domains from spider flagelliform
      silk protein and the Ca(2+) binding domain of lipase Lip A from Serratia
      marcescens . After carefully comparing the primary structures of both sequences,
      we rationally designed a newly sequenced eD(2) by "hiding" the ion binding
      sequence in the silk structure sequence. This helped avoid redundancy, and the
      new sequence had properties of both model sequences. In water, eD(2) formed
      uniform spherical agglomerates with a beta-spiral structure. Triggered by Ca(2+),
      eD(2) formed nanofibers with higher compliance and thermal stability. We
      demonstrated the specialties of this novel peptide design by changing the pH,
      using other metal ions, and mutating the model sequence.

PMID- 21080626
TI  - Ruthenium-catalyzed domino redox bicycloisomerization. An atom-economical
      synthesis of [3.1.0]- and [4.1.0]carbo- and heterocycles.

PMID- 21080628
TI  - Bitter-tasting and kokumi-enhancing molecules in thermally processed avocado
      (Persea americana Mill.).
AB  - Sequential application of solvent extraction and RP-HPLC in combination with
      taste dilution analyses (TDA) and comparative TDA, followed by LC-MS and 1D/2D
      NMR experiments, led to the discovery of 10 C(17)-C(21) oxylipins with 1,2,4
      trihydroxy-, 1-acetoxy-2,4-dihydroxy-, and 1-acetoxy-2-hydroxy-4-oxo motifs,
      respectively, besides 1-O-stearoyl-glycerol and 1-O-linoleoyl-glycerol as bitter
      tasting compounds in thermally processed avocado (Persea americana Mill.). On the
      basis of quantitative data, dose-over-threshold (DoT) factors, and taste re
      engineering experiments, these phytochemicals, among which 1-acetoxy-2-hydroxy-4
      oxo-octadeca-12-ene was found with the highest taste impact, were confirmed to be
      the key contributors to the bitter off-taste developed upon thermal processing of
      avocado. For the first time, those C(17)-C(21) oxylipins exhibiting a 1-acetoxy
      2,4-dihydroxy- and a 1-acetoxy-2-hydroxy-4-oxo motif, respectively, were
      discovered to induce a mouthfulness (kokumi)-enhancing activity in sub-bitter
      threshold concentrations.

PMID- 21080629
TI  - Novel chimeric histone deacetylase inhibitors: a series of lapatinib hybrides as
      potent inhibitors of epidermal growth factor receptor (EGFR), human epidermal
      growth factor receptor 2 (HER2), and histone deacetylase activity.
AB  - Reversible lysine-specific acetylation has been described as an important
      posttranslational modification, regulating chromatin structure and
      transcriptional activity in the case of core histone proteins. Histone
      deacetylases (HDAC) are considered as a promising target for anticancer drug
      development, with 2a as pan-HDAC inhibitor approved for cutanous T-cell lymphoma
      therapy and several other HDAC inhibitors currently in preclinical and clinical
      development. Protein kinases are a well-established target for cancer therapy
      with the EGFR/HER2 inhibitor 5 approved for treatment of advanced, HER2 positive
      breast cancer as a prominent example. In the present report, we present a novel
      strategy for cancer drug development by combination of EGFR/HER2 kinase and HDAC
      inhibitory activity in one molecule. By combining the structural features of 5
      with an (E)-3-(aryl)-N-hydroxyacrylamide motif known from HDAC inhibitors like 1
      or 3, we obtained selective inhibitors for both targets with potent cellular
      activity (target inhibition and cytotoxicity) of selected compounds 6a and 6c. By
      combining two distinct pharmacologically properties in one molecule, we postulate
      a broader activity spectrum and less likelihood of drug resistance in cancer
      patients.

PMID- 21080630
TI  - SIRT1 modulation as a novel approach to the treatment of diseases of aging.

PMID- 21080631
TI  - New theoretical framework for designing nonionic surfactant mixtures that exhibit
      a desired adsorption kinetics behavior.
AB  - How does one design a surfactant mixture using a set of available surfactants
      such that it exhibits a desired adsorption kinetics behavior? The traditional
      approach used to address this design problem involves conducting trial-and-error
      experiments with specific surfactant mixtures. This approach is typically time
      consuming and resource-intensive and becomes increasingly challenging when the
      number of surfactants that can be mixed increases. In this article, we propose a
      new theoretical framework to identify a surfactant mixture that most closely
      meets a desired adsorption kinetics behavior. Specifically, the new theoretical
      framework involves (a) formulating the surfactant mixture design problem as an
      optimization problem using an adsorption kinetics model and (b) solving the
      optimization problem using a commercial optimization package. The proposed
      framework aims to identify the surfactant mixture that most closely satisfies the
      desired adsorption kinetics behavior subject to the predictive capabilities of
      the chosen adsorption kinetics model. Experiments can then be conducted at the
      identified surfactant mixture condition to validate the predictions. We
      demonstrate the reliability and effectiveness of the proposed theoretical
      framework through a realistic case study by identifying a nonionic surfactant
      mixture consisting of up to four alkyl poly(ethylene oxide) surfactants
      (C(10)E(4), C(12)E(5), C(12)E(6), and C(10)E(8)) such that it most closely
      exhibits a desired dynamic surface tension (DST) profile. Specifically, we use
      the Mulqueen-Stebe-Blankschtein (MSB) adsorption kinetics model (Mulqueen, M.;
      Stebe, K. J.; Blankschtein, D. Langmuir 2001, 17, 5196-5207) to formulate the
      optimization problem as well as the SNOPT commercial optimization solver to
      identify a surfactant mixture consisting of these four surfactants that most
      closely exhibits the desired DST profile. Finally, we compare the experimental
      DST profile measured at the surfactant mixture condition identified by the new
      theoretical framework with the desired DST profile and find good agreement
      between the two profiles.

PMID- 21080632
TI  - Effects of inherent/enhanced solid acidity and morphology of diatomite templates
      on the synthesis and porosity of hierarchically porous carbon.
AB  - The inherent or enhanced solid acidity of raw or activated diatomite is found to
      have significant effects on the synthesis of hierarchically porous diatomite
      templated carbon with high surface area and special porous structure. The solid
      acidity makes raw/activated diatomite a catalyst for the generation of porous
      carbon, and the porous parameters of the carbon products are strongly dependent
      on the solid acidity of diatomite templates. The morphology of diatomite also
      dramatically affects the textural structure of porous carbon. Two types of
      macroporous structures in the carbon product, the partially solid pillars and the
      ordered hollow tubes, derive from the replication of the central and the edge
      pores of diatom shell, respectively. The hierarchically porous carbon shows good
      capability for the adsorption of solvent naphtha and H(2), enabling potential
      applications in adsorption and gas storage.

PMID- 21080633
TI  - An empirically validated analytical model of droplet dynamics in electrowetting
      on dielectric devices.
AB  - Explicit analytical models that describe the capillary force on confined droplets
      actuated in electrowetting on dielectric devices and the reduction in that force
      by contact angle hysteresis as a function of the three-dimensional shape of the
      droplet interface are presented. These models are used to develop an analytical
      model for the transient position and velocity of the droplet. An order of
      magnitude analysis showed that droplet motion could be modeled using the driving
      capillary force opposed by contact angle hysteresis, wall shear, and contact line
      friction. Droplet dynamics were found to be a function of gap height, droplet
      radius, surface tension, fluid density, the initial and deformed contact angles,
      contact angle hysteresis, and friction coefficients pertaining to viscous wall
      friction and contact line friction. The first four parameters describe the device
      geometry and fluid properties; the remaining parameters were determined
      experimentally. Images of the droplet during motion were used to determine the
      evolution of the shape, position, and velocity of the droplet with time.
      Comparisons between the measured and predicted results show that the proposed
      model provides good accuracy over a range of practical voltages and droplet
      aspect ratios.

PMID- 21080634
TI  - Syntheses and properties of two-dimensional, dicationic nonlinear optical
      chromophores based on pyrazinyl cores.
AB  - Six new dicationic 2D nonlinear optical (NLO) chromophores with pyrazinyl
      pyridinium electron acceptors have been synthesized by nucleophilic substitutions
      of 2,6-dichloropyrazine with pyridyl derivatives. These compounds have been
      characterized as their PF(6)(-) salts by using various techniques including
      electronic absorption spectroscopy and cyclic voltammetry. Large red shifts in
      the intense, pi -> pi* intramolecular charge-transfer (ICT) transitions on
      replacing -OMe with -NMe(2) substituents arise from the stronger pi-electron
      donor ability of the latter. Each compound shows a number of redox processes
      which are largely irreversible. Single crystal X-ray structures have been
      determined for five salts, including two nitrates, all of which adopt
      centrosymmetric packing arrangements. Molecular first hyperpolarizabilities beta
      have been determined by using femtosecond hyper-Rayleigh scattering at 880 and
      800 nm, and depolarization studies show that the NLO responses of the symmetric
      species are strongly 2D, with dominant "off-diagonal" beta(zyy) components. Stark
      (electroabsorption) spectroscopic measurements on the ICT bands afford estimated
      static first hyperpolarizabilities beta(0). The directly and indirectly derived
      beta values are large, and the Stark-derived beta(0) response for one of the new
      salts is several times greater than that determined for (E)-4'-(dimethylamino)-N
      methyl-4-stilbazolium hexafluorophosphate. These Stark spectroscopic studies also
      permit quantitative comparisons with related 2D, binuclear Ru(II) ammine complex
      salts.

PMID- 21080635
TI  - Nitrile functionalized methimazole-based ionic liquids.
AB  - The alkylation reaction of 2-mercapto-1-methylimidazole 1b with 2
      chloroacetonitrile and 2-chloropropionitrile produced S-alkyl methimazole
      chlorides 2a and 2b which were subjected to anion metathesis with lithium
      bis(trifluoromethanesulfonyl)amide, LiNTf(2), to afford nitrile functionalized
      methimazole-based room temperature ionic liquids 3a and 3b in 94% and 89% yields,
      respectively. Ionic liquids 3a and 3b have reasonably wide electrochemical
      windows. The efficient extraction of Ag(+) from aqueous media into 3a and 3b is
      also reported.

PMID- 21080636
TI  - Pyrene-assisted efficient photolysis of disulfide bonds in DNA-based molecular
      engineering.
AB  - An efficient pyrene-assisted method has been developed for the photolysis of
      disulfide bonds, with 77% of disulfides cleaved after only 20 min of irradiation
      (0.3W) at 350 nm. By employing a DNA framework, it was possible to observe both a
      distance-dependent cleavage pathway and a radical-forming photoreaction
      mechanism. To demonstrate the biomedical applications of such pyrene disulfide
      molecular assemblies, a DNA micelle structure and DNAzyme analog were further
      studied. Rapid photodriven disassembly of DNA micelles was achieved, allowing the
      further design of controlled pharmaceutical release at the target region and at a
      specific time. The DNAzyme analog can carry out multiple turnover reactions that
      follow the Michaelis-Menten equation, with a kcat of 10.2 min(-1) and a KM of
      46.3 MUM (0.3W 350 nm light source), comparable to that of common DNAzymes, e.g.,
      8-17 DNAzyme.

PMID- 21080637
TI  - Flow-through vs flow-over: analysis of transport and binding in nanohole array
      plasmonic biosensors.
AB  - We quantify the efficacy of flow-through nanohole sensing, as compared to the
      established flow-over format, through scaling analysis and numerical simulation.
      Nanohole arrays represent a growing niche within surface plasmon resonance-based
      sensing methods, and employing the nanoholes as nanochannels can enhance
      transport and analytical response. The additional benefit offered by flow-through
      operation is, however, a complex function of operating parameters and application
      specific binding chemistry. Compared here are flow-over sensors and flow-through
      nanohole array sensors with equivalent sensing area, where the nanohole array
      sensing area is taken as the inner-walls of the nanoholes. The footprints of the
      sensors are similar (e.g., a square 20 MUm wide flow-over sensor has an
      equivalent sensing area as a square 30 MUm wide array of 300 nm diameter
      nanoholes with 450 nm periodicity in a 100 nm thick gold film). Considering
      transport alone, an analysis here shows that given equivalent sensing area and
      flow rate the flow-through nanohole format enables greatly increased flux of
      analytes to the sensing surface (e.g., 40-fold for the case of Q = 10 nL/min).
      Including both transport and binding kinetics, a computational model, validated
      by experimental data, provides guidelines for performance as a function of
      binding time constant, analyte diffusivity, and running parameters. For common
      binding kinetics and analytes, flow-through nanohole arrays offer ~10-fold
      improvement in response time, with a maximum of 20-fold improvement for small
      biomolecules with rapid kinetics.

PMID- 21080639
TI  - Structure-based color of natural petals discriminated by polymer replication.
AB  - The optical appearance of many flowers in nature relies on their inherent
      pigments ("chemical color") as well as on the surface structure of the epidermis
      ("structural color"). The structural color is created by a combination of regular
      and irregular micro- and nanosized features. With a red rose petal as a
      biological template, we have separated the structural coloration from the
      chemical coloration by reproducing the petal's intricate surface structure in a
      pigment-free polymer. UV-vis reflectance measurements of the templates showed
      that the pigment-induced chemical coloration of the red-rose petal results in
      intense absorption and reflection in the green (~550 nm) and red (~700 nm)
      spectral region, respectively. The micro- and nanosized structural hierarchy on
      the petal surface, on the other hand, induced a modulation of the optical
      reflectivity and a filtering effect in specific wavelength ranges. More notably,
      we observed that a variation in the size of the micro/nanostructures on the petal
      surface leads to an effective modulation of the reflectance. These results could
      provide useful tips for the design of bioinspired optical devices, emulating
      natural petal structures.

PMID- 21080638
TI  - Competition-mediated pyrene-switching aptasensor: probing lysozyme in human serum
      with a monomer-excimer fluorescence switch.
AB  - Lysozyme (Lys) plays crucial roles in the innate immune system, and the detection
      of Lys in urine and serum has considerable clinical importance. Traditionally,
      the presence of Lys has been detected by immunoassays; however, these assays are
      limited by the availability of commercial antibodies and tedious protein
      modification and prior sample purification. To address these limitations, we
      report here the design, synthesis, and application of a competition-mediated
      pyrene-switching aptasensor for selective detection of Lys in buffer and human
      serum. The detection strategy is based on the attachment of pyrene molecules to
      both ends of a hairpin DNA strand, which becomes the partially complementary
      competitor to an anti-Lys aptamer. In the presence of target Lys, the aptamer
      hybridizes with part of the competitor, which opens the hairpin such that both
      pyrene molecules are spatially separated. In the presence of target Lys, however,
      the competitor is displaced from the aptamer by the target, subsequently forming
      an initial hairpin structure. This brings the two pyrene moieties into close
      proximity to generate an excimer, which, in turn, results in a shift of
      fluorescence emission from ca. 400 nm (pyrene monomer) to 495 nm (pyrene
      excimer). The proposed method for Lys detection showed sensitivity as low as 200
      pM and high selectivity in buffer. When measured by a steady-state fluorescence
      spectrum, the detection of Lys in human serum showed a strong fluorescent
      background, which obscured detection of the excimer signal. However, time
      resolved emission measurement (TREM) supported the potential of the method in
      complex environments with background fluorescence by demonstrating the temporal
      separation of probe fluorescence emission decay from the intense background
      signal. We have also demonstrated that the same strategy can be applied to the
      detection of small biomolecules such as adenosine triphosphate (ATP), showing the
      generality of our approach. Therefore, the competition-mediated pyrene-switching
      aptasensor is promising to have potential for clinical and forensic applications.

PMID- 21080640
TI  - Hollow core-porous shell structure poly(acrylic acid) nanogels with a superhigh
      capacity of drug loading.
AB  - Poly(acrylic acid) (PAA) nanogels with a hollow core-porous shell structure were
      prepared by the direct polymerization of an acrylic acid monomer in the presence
      of hydroxypropylcellulose (HPC) and a cross-linking agent, N,N
      methylenebisacrylamide, followed by removal of HPC from the generated HPC-PAA
      nanoparticles in a basic environment. The properties of PAA nanogel were
      characterized by dynamic light scattering, FT-IR, transmission electron
      microscopy, and atomic force microscopy. It is found that the nanogels have a
      hollow core-porous shell structure. Protein, bovine serum albumin (BSA), and an
      antitumor agent, doxorubicin hydrochloride, were used as model drugs to
      investigate their loading abilities as versatile drug-delivery vehicles. The
      nanogel exhibits surprisingly high loading ability to both protein and small
      molecular drugs. For example, the maximum BSA loading capacity of PAA nanogel can
      reach as high as 800% (i.e., 1 mg of nanogel can load about 8.0 mg of BSA). This
      high loading capacity may be related with the hollow core-porous shell structure
      of PAA nanogels. PAA nanogels have also shown sustained drug release properties
      and can cross biological barriers to deliver loaded cargo inside cells.
      Considering the high stability of the materials, simple and mild preparation
      procedure, high loading capacity, sustained-release property, and ability to
      protect biological agents from denaturation, PAA nanogels should be promising
      drug-delivery carriers for drug-delivery systems.

PMID- 21080641
TI  - Pore space partition and charge separation in cage-within-cage indium-organic
      frameworks with high CO2 uptake.
AB  - The integration of negatively charged single-metal building blocks {In(CO2)4} and
      positively charged trimeric clusters {In3O} leads to three unique cage-within
      cage-based porous materials, which exhibit not only high hydrothermal, thermal,
      and photochemical stability but also attractive structural features contributing
      to a very high CO2 uptake capacity of up to 119.8 L/L at 273 K and 1 atm.

PMID- 21080642
TI  - Catechin derivatives from Parapiptadenia rigida with in vitro wound-healing
      properties.
AB  - Analysis of the ethanolic extract of the bark from Parapiptadenia rigida resulted
      in the isolation of the new catechin derivatives 4',3''-di-O-methylapocynin-D
      (10), 4',3''-di-O-methylapocynin-B (11), epigallocatechin-3-O-ferulate (8), and
      4'-O-methylepigallocatechin-3-O-ferulate (9) and the catechins 4'-O
      methylepigallocatechin-3-O-gallate (6) and 4'-O-methylepicatechin-3-O-gallate
      (7). These compounds, isolated for the first time from a natural source, are
      accompanied by the five known catechins 4'-O-methylgallocatechin (1), 4'-O
      methylepigallocatechin (2), 3'-O-methylepicatechin (3), epigallocatechin-3-O
      gallate (4), and epicatechin-3-O-gallate (5). Compounds 5 and 7 displayed
      promising wound-healing effects in a scratch assay. Some of the catechin
      derivatives showed inhibitory effects on NF-kappaB DNA binding and p38alpha MAPK
      activity.

PMID- 21080643
TI  - Spectroscopic characterization and antiproliferative activity on HepG2 human
      hepatoblastoma cells of flavonoid C-glycosides from Petrorhagia velutina.
AB  - Eight flavonoid C-glycosides, including three new analogues, have been isolated
      from leaf and root methanolic extracts of Petrorhagia velutina, a Mediterranean
      herbaceous plant. The antiproliferative activity against human hepatoblastoma
      cancer cell line HepG2 has been analyzed by the MTT (3-(4,5-dimethyl-2-thiazolyl)
      2,5-diphenyl-2H-tetrazolium bromide) test. Isoorientin (4) significantly reduces
      the proliferation of HepG2 cells as determined by the complete conversion of the
      tetrazolium probe into formazan after 48 h of exposure.

PMID- 21080644
TI  - Flood hydrology and methylmercury availability in coastal plain rivers.
AB  - Mercury (Hg) burdens in top-predator fish differ substantially between adjacent
      South Carolina Coastal Plain river basins with similar wetlands coverage. In the
      Congaree River, floodwaters frequently originate in the Blue Ridge and Piedmont
      regions, where wetlands coverage and surface water dissolved methylmercury (MeHg)
      concentrations are low. Piedmont-driven flood events can lead to downward
      hydraulic gradients in the Coastal Plain riparian wetland margins, inhibiting
      MeHg transport from wetland sediments, and decreasing MeHg availability in the
      Congaree River habitat. In the adjacent Edisto River basin, floodwaters originate
      only within Coastal Plain sediments, maintaining upward hydraulic gradients even
      during flood events, promoting MeHg transport to the water column, and enhancing
      MeHg availability in the Edisto River habitat. These results indicate that flood
      hydrodynamics contribute to the variability in Hg vulnerability between Coastal
      Plain rivers and that comprehensive regional assessment of the relationship
      between flood hydrodynamics and Hg risk in Coastal Plain streams is warranted.

PMID- 21080646
TI  - Protodeboronation of tertiary boronic esters: asymmetric synthesis of tertiary
      alkyl stereogenic centers.
AB  - While tertiary boranes undergo efficient protodeboronation with carboxylic acids,
      tertiary boronic esters do not. Instead, we have discovered that CsF with 1.1
      equiv of H2O (on tertiary diarylalkyl boronic esters) or TBAF.3H2O (on tertiary
      aryldialkyl boronic esters) effect highly efficient protodeboronation of tertiary
      boronic esters with essentially complete retention of configuration. Furthermore,
      substituting D2O for H2O provides ready access to deuterium-labeled
      enantioenriched tertiary alkanes. The methodology has been applied to a short
      synthesis of the sesquiterpene, (S)-turmerone.

PMID- 21080645
TI  - One-pot thioether formation from S-nitrosothiols.
AB  - Protein S-nitrosation is an important post-translational modification. However,
      the detection of S-nitrosation is still problematic because S-nitrosation
      products, that is, S-nitrosothiols, are unstable species. Here a new reaction
      which can selectively convert unstable S-nitrosothiols to stable thioethers in
      one-pot under very mild conditions is reported. This reaction has the potential
      to be applied in the detection of protein S-nitrosation.

PMID- 21080647
TI  - Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N
      hydroxypyrimidine-5-carboxamide (CHR-3996), a class I selective orally active
      histone deacetylase inhibitor.
AB  - A novel series of HDAC inhibitors demonstrating class I subtype selectivity and
      good oral bioavailability is described. The compounds are potent enzyme
      inhibitors (IC50 values less than 100 nM), and improved activity in cell
      proliferation assays was achieved by modulation of polar surface area (PSA)
      through the introduction of novel linking groups. Employing oral pharmacokinetic
      studies in mice, comparing drug levels in spleen to plasma, we selected compounds
      that were tested for efficacy in human tumor xenograft studies based on their
      potential to distribute into tumor. One compound, 21r (CHR-3996), showed good
      oral activity in these models, including dose-related activity in a LoVo
      xenograft. In addition 21r showed good activity in combination with other
      anticancer agents in in vitro studies. On the basis of these results, 21r was
      nominated for clinical development.

PMID- 21080648
TI  - Correlations between mechanical and electrical properties of polythiophenes.
AB  - The elastic moduli of polythiophenes, regioregular poly(3-hexylthiophene) (P3HT)
      and poly-(2,5-bis(3-alkylthiophene-2-yl)thieno[3,2-b]thiophene) (pBTTT), are
      compared to their field effect mobility showing a proportional trend. The elastic
      moduli of the films are measured using a buckling-based metrology, and the
      mobility is determined from the electrical characteristics of bottom contact thin
      film transistors. Moreover, the crack onset strain of pBTTT films is shown to be
      less than 2.5%, whereas that of P3HT is greater than 150%. These results show
      that increased long-range order in polythiophene semiconductors, which is
      generally thought to be essential for improved charge mobility, can also stiffen
      and enbrittle the film. This work highlights the critical role of quantitative
      mechanical property measurements in guiding the development of flexible organic
      semiconductors.

PMID- 21080649
TI  - Calculator tool for determining greenhouse gas emissions for biosolids processing
      and end use.
AB  - A greenhouse gas (GHG) calculator tool (Biosolids Emissions Assessment Model,
      BEAM) was developed for the Canadian Council of Ministers of the Environment to
      allow municipalities to estimate GHG emissions from biosolids management. The
      tool was developed using data from peer reviewed literature and municipalities.
      GHG emissions from biosolids processing through final end use/disposal were
      modeled. Emissions from nine existing programs in Canada were estimated using the
      model. The program that involved dewatering followed by combustion resulted in
      the highest GHG emissions (Mg CO(2)e 100 Mg(-1) biosolids (dry wt.). The programs
      that had digestion followed by land application resulted in the lowest emissions
      (-26 and -23 Mg CO(2)e 100 Mg(-1) biosolids (dry wt.). Transportation had
      relatively minor effects on overall emissions. The greatest areas of uncertainty
      in the model include N(2)O emissions from land application and biosolids
      processing. The model suggests that targeted use of biosolids and optimizing
      processes to avoid CH(4) and N(2)O emissions can result in significant GHG
      savings.

PMID- 21080650
TI  - Crystalline silicon nanotubes and their connections with gold nanowires in both
      linear and branched topologies.
AB  - Silicon, being in the same group in the periodic table as carbon, plays a key
      role in modern semiconductor industry. However, unlike carbon nanotube (NT),
      progress remains relatively slow in silicon NT (SiNT) and SiNT-based
      heteroarchitectures, which would be the fundamental building blocks of various
      nanoscale circuits, devices, and systems. Here, we report the synthesis of linear
      and branched crystalline SiNTs via porous anodic aluminum oxide (AAO) self
      catalyzed growth and postannealing, and the connection of crystalline SiNTs and
      gold nanowires (AuNWs) via a combinatorial process of electrodepositing AuNWs
      with predesired length and location in the channels of the AAO template and
      subsequent AAO self-catalyzed and postannealing growth of SiNTs in the remaining
      empty channels adjacent to the AuNWs. Using the approach, a large variety of two
      segment AuNW/SiNT and three-segment SiNT/AuNW/SiNT heteronanostructures with both
      linear and branched topologies have been achieved, paving the way for the
      rational design and fabrication of SiNT-based nanocircuits, nanodevices, and
      multifunctional nanosystems in the future.

PMID- 21080651
TI  - One pot synthesis of heterometallic 3d-3d azide coordination architectures:
      effect of the single-ion anisotropy.
AB  - Five new isomorphic three-dimensional (3D) heterometallic 3d-3d azide complexes,
      [CuNi(1-x)Co(x)(N(3))(2)(isonic)(2)](infinity) (x = 0 for 1, x = 0.3 for 2, x =
      0.5 for 3, x = 0.6 for 4, and x = 1 for 5), were obtained by assembling Cu(II),
      M(II) (Ni(II) and Co(II)), azide, and pyridyl carboxylate in hydrothermal
      condition. The 3D structure can be described as end on (EO) azide and syn,syn
      carboxylates mixed bridged alternate Cu-M chains linked by the pyridyl groups.
      Dominant ferromagnetic interactions were observed between the Cu(II) and M(II)
      ions in the chains. At low temperature diverse magnetic phenomena were presented
      in those complexes. As the Ni(II) ions were replaced by Co(II) ions with large
      anisotropy, the magnetism of the complexes change gradually from metamagnet to
      single-chain magnet (SCM)-like behaviors.

PMID- 21080652
TI  - Graphene nanoribbon composites.
AB  - It is well established that pristine multiwalled carbon nanotubes offer poor
      structural reinforcement in epoxy-based composites. There are several reasons for
      this which include reduced interfacial contact area since the outermost nanotube
      shields the internal tubes from the matrix, poor wetting and interfacial adhesion
      with the heavily cross-linked epoxy chains, and intertube slip within the
      concentric nanotube cylinders leading to a sword-in-sheath type failure. Here we
      demonstrate that unzipping such multiwalled carbon nanotubes into graphene
      nanoribbons results in a significant improvement in load transfer effectiveness.
      For example, at ~0.3% weight fraction of nanofillers, the Young's modulus of the
      epoxy composite with graphene nanoribbons shows ~30% increase compared to its
      multiwalled carbon nanotube counterpart. Similarly the ultimate tensile strength
      for graphene nanoribbons at ~0.3% weight fraction showed ~22% improvement
      compared to multiwalled carbon nanotubes at the same weight fraction of
      nanofillers in the composite. These results demonstrate that unzipping
      multiwalled carbon nanotubes into graphene nanoribbons can enable their
      utilization as high-performance additives for mechanical properties enhancement
      in composites that rival the properties of singlewalled carbon nanotube
      composites yet at an order of magnitude lower cost.

PMID- 21080653
TI  - Compelling computational evidence for the concerted cyclization of the ABC rings
      of hopene from protonated squalene.
AB  - The long-standing question of what is the nature of the cyclization of squalene
      to form tetracyclic and pentacyclic triterpenes has been addressed
      computationally. Using the DFT method with an intrinsic reaction coordinate
      calculation, we find that the first three rings of protonated squalene were
      formed without the intermediacy of mono- or bicyclic carbocations. The
      cyclization, calculated in the gas phase, proceeds in a highly asynchronous,
      concerted reaction to yield the tricyclic, tertiary carbocation with a 5-membered
      C ring. The fourth double bond of squalene is not properly oriented for the ring
      expansion of the C ring in concert with the formation of the 5-membered ring.

PMID- 21080655
TI  - Tensile film stress of parylene deposited on liquid.
AB  - We found that liquid droplets encapsulated by Parylene deposited directly on a
      liquid surface deformed toward spherical shapes during Parylene deposition. This
      deformation suggested that the film stress was tensile. We calculated the film
      stress of such Parylene films by studying the surface mean curvature of the
      droplet shape and found the film stress measured about 0.7-0.9 MPa tensile. This
      film stress is of opposite type to that of as-deposited Parylene films deposited
      on solid substrates, which was compressive. This difference might indicate a
      profound change of the Parylene polymer due to the use of liquid surface as
      deposition substrate. The tensile film stress and its effect on the droplet shape
      also have implications in the fabrication and operation of Parylene microdevices
      that have encapsulated liquid structures such as microlens or micropumps.

PMID- 21080656
TI  - The role of electrostatic interactions in protease surface diffusion and the
      consequence for interfacial biocatalysis.
AB  - This study examines the influence of electrostatic interactions on enzyme surface
      diffusion and the contribution of diffusion to interfacial biocatalysis. Surface
      diffusion, adsorption, and reaction were investigated on an immobilized bovine
      serum albumin (BSA) multilayer substrate over a range of solution ionic strength
      values. Interfacial charge of the enzyme and substrate surface was maintained by
      performing the measurements at a fixed pH; therefore, electrostatic interactions
      were manipulated by changing the ionic strength. The interfacial processes were
      investigated using a combination of techniques: fluorescence recovery after
      photobleaching, surface plasmon resonance, and surface plasmon fluorescence
      spectroscopy. We used an enzyme charge ladder with a net charge ranging from -2
      to +4 with respect to the parent to systematically probe the contribution of
      electrostatics in interfacial enzyme biocatalysis on a charged substrate. The
      correlation between reaction rate and adsorption was determined for each charge
      variant within the ladder, each of which displayed a maximum rate at an
      intermediate surface concentration. Both the maximum reaction rate and adsorption
      value at which this maximum rate occurs increased in magnitude for the more
      positive variants. In addition, the specific enzyme activity increased as the
      level of adsorption decreased, and for the lowest adsorption values, the specific
      enzyme activity was enhanced compared to the trend at higher surface
      concentrations. At a fixed level of adsorption, the specific enzyme activity
      increased with positive enzyme charge; however, this effect offers diminishing
      returns as the enzyme becomes more highly charged. We examined the effect of
      electrostatic interactions on surface diffusion. As the binding affinity was
      reduced by increasing the solution ionic strength, thus weakening electrostatic
      interaction, the rate of surface diffusion increased considerably. The
      enhancement in specific activity achieved at the lowest adsorption values is
      explained by the substantial rise in surface diffusion at high ionic strength due
      to decreased interactions with the surface. Overall, knowledge of the
      electrostatic interactions can be used to control surface parameters such as
      surface concentration and surface diffusion, which intimately correlate with
      surface biocatalysis. We propose that the maximum reaction rate results from a
      balance between adsorption and surface diffusion. The above finding suggests
      enzyme engineering and process design strategies for improving interfacial
      biocatalysis in industrial, pharmaceutical, and food applications.

PMID- 21080657
TI  - Molecular dynamics study of the structures and dynamics of the iodine molecules
      confined in AlPO(4)-11 crystals.
AB  - Structural and dynamical properties of iodine molecules incorporated in one
      dimensional elliptic channels of AlPO(4)-11 (AEL) crystals were studied by means
      of molecular dynamics (MD) simulations. It was found that the iodine molecules in
      the AEL channels are restricted in the (101) planes with only two favorite
      orientations: lying along the channels and standing along the major axes of the
      ellipses, which are well consistent with the experimental observations. In
      addition, the iodine structures are largely dependent on the loading level: with
      the increase of loading, the iodine specimens change their structures accordingly
      from isolated molecules as in the gas phase to single molecular chains and
      molecular ribbon sheets. The molecular ribbon sheets are composed of equally
      distributed and parallel molecules as in the iodine crystals. The simulation
      results show that the standing iodine molecules in the AEL channels are well
      restricted due to both the appropriate size of ellipses and their alternation
      throughout the channels. They can diffuse along the channels only after
      overcoming the rotational barriers to become lying molecules, which indicate that
      the iodine molecules in the ribbon sheets can keep the configurations without
      rotational and translational motion. The confined iodine molecules with such
      structures and properties may be used to improve the accuracy of the frequency
      standards.

PMID- 21080654
TI  - Peroxynitrite mediates active site tyrosine nitration in manganese superoxide
      dismutase. Evidence of a role for the carbonate radical anion.
AB  - Protein tyrosine nitration has been observed in a variety of human diseases
      associated with oxidative stress, such as inflammatory, neurodegenerative, and
      cardiovascular conditions. However, the pathways leading to nitration of tyrosine
      residues are still unclear. Recent studies have shown that peroxynitrite (PN),
      produced by the reaction of superoxide and nitric oxide, can lead to protein
      nitration and inactivation. Tyrosine nitration may also be mediated by nitrogen
      dioxide produced by the oxidation of nitrite by peroxidases. Manganese superoxide
      dismutase (MnSOD), which plays a critical role in cellular defense against
      oxidative stress by decomposing superoxide within mitochondria, is nitrated and
      inactivated under pathological conditions. In this study, MnSOD is shown to
      catalyze PN-mediated self-nitration. Direct, spectroscopic observation of the
      kinetics of PN decay and nitrotyrosine formation (k(cat) = 9.3 * 10(2) M(-1) s(
      1)) indicates that the mechanism involves redox cycling between Mn(2+) and
      Mn(3+), similar to that observed with superoxide. Distinctive patterns of
      tyrosine nitration within MnSOD by various reagents were revealed and quantified
      by MS/MS analysis of MnSOD trypsin digest peptides. These analyses showed that
      three of the seven tyrosine residues of MnSOD (Tyr34, Tyr9, and Tyr11) were the
      most susceptible to nitration and that the relative amounts of nitration of these
      residues varied widely depending upon the nature of the nitrating agent. Notably,
      nitration mediated by PN, in both the presence and absence of CO2, resulted in
      nitration of the active site tyrosine, Tyr34, while nitration by freely diffusing
      nitrogen dioxide led to surface nitration at Tyr9 and Tyr11. Flux analysis of the
      nitration of Tyr34 by PN-CO2 showed that the nitration rate coincided with the
      kinetics of the reaction of PN with CO2. These kinetics and the 20-fold increase
      in the efficiency of tyrosine nitration in the presence of CO2 suggest a specific
      role for the carbonate radical anion (*CO3(-)) in MnSOD nitration by PN. We also
      observed that the nitration of Tyr34 caused inactivation of the enzyme, while
      nitration of Tyr9 and Tyr11 did not interfere with the superoxide dismutase
      activity. The loss of MnSOD activity upon Tyr34 nitration implies that the
      responsible reagent in vivo is peroxynitrite, acting either directly or through
      the action of *CO3(-).

PMID- 21080658
TI  - Bulk synthesis of polymer-inorganic colloidal clusters.
AB  - We describe a procedure to synthesize colloidal clusters with polyhedral
      morphologies in high yield (liter quantities at up to 70% purity) using a
      combination of emulsion polymerization and inorganic surface chemistry. We show
      that the synthesis initially used for silica-polystyrene hybrid clusters can be
      generalized to create clusters from other inorganic and polymer particles. We
      also show that high yields of particular morphologies can be obtained by precise
      control of the inorganic seed particle size, a finding that can be explained
      using a hard-sphere packing model. These clusters can be further chemically
      modified for a variety of applications. Introducing a cross-linker leads to
      colloidal clusters that can be index matched in an appropriate solvent, allowing
      them to be used for particle tracking or optical studies of colloidal self
      assembly. Also, depositing a thin silica layer on these colloids allows the
      surface properties to be controlled using silane chemistry.

PMID- 21080659
TI  - Intercalative poly(carbazole) precursor electropolymerization within hybrid
      nanostructured titanium oxide ultrathin films.
AB  - A protocol for nanostructuring and electropolymerization of a hybrid
      semiconductor polycarbazole-titanium oxide ultrathin film is described. Ultrathin
      (<100 nm) films based on polycarbazole precursor polyelectrolytes and titanium
      oxide (TiOx) have been fabricated by combining the layer-by-layer (LbL) and
      surface sol-gel layering techniques. Film growth was followed and confirmed
      through UV-vis spectroscopy, ellipsometry and quartz crystal microbalance with
      dissipation (QCM-D). Subsequent anodic electrochemical oxidation of the carbazole
      pendant units afforded a conjugated polymer network (CPN) film within
      intercalating TiOx layers of cross-linked and pi-conjugated carbazole units.
      Cyclic voltammetry (CV), UV-vis, and fluorescence spectroscopy measurements
      confirmed this process. The LbL-driven polyelectrolyte deposition process
      resulted in a quantified electrochemical response, proportional to the number of
      layers, while the TiOx acted as a dielectric spacer limiting electron transfer
      kinetics and attenuating energy transfer in fluorescence. Electro-optical
      properties were compared with other polycarbazole thin film materials with
      respect to bandgap energy (Eg). The straightforward protocol in film
      nanostructuring and barrier/dielectric properties of the inorganic oxide slab
      (denoted here as, TiOx) should enable applications in organic light-emitting
      diodes (OLEDs), dielectric mirrors, planar waveguides, and photovoltaic devices
      for these hybrid ultrathin films.

PMID- 21080660
TI  - Electropolymerized molecularly imprinted polymer films of a bis-terthiophene
      dendron: folic acid quartz crystal microbalance sensing.
AB  - A folic acid sensor was prepared via an electropolymerized molecularly imprinted
      polymer (E-MIP) film of a bis-terthiophene dendron on a quartz crystal
      microbalance (QCM). The cyclic voltammetry (CV) electrodeposition of the
      imprinted polymer film was monitored by electrochemical QCM or E-QCM, enabling in
      situ monitoring and characterization of E-MIP film formation and the viscoelastic
      behavior of the film. A key component of the E-MIP process is the use of a
      bifunctional monomer design to precomplex with the template and function as a
      cross-linker. The complex was electropolymerized and cross-linked by CV to form a
      polythiophene matrix. Stable cavities were formed that specifically fit the size
      and shape of the folic acid template. The same substrate surface was used for
      folic acid sensing. The predicted geometry of the 1:2 folic acid/terthiophene
      complex was obtained through semiempirical AM1 quantum calculations. The
      analytical performance, expressed through the figures of merit, of the sensor in
      aqueous solutions of the analyte was investigated. A relatively good linearity,
      R(2) = 0.985, was obtained within the concentration range 0-100 MUM folic acid.
      The detection limit was found to be equal to 15.4 MUM (6.8 MUg). The relative
      cross selectivity of the folic acid imprinted polymer against the three molecules
      follows this trend: pteroic acid (= 50%) > caffeine (= 41%) > theophylline (=
      6%). The potential and limitations of the E-MIP method were also discussed.

PMID- 21080661
TI  - Condensation/evaporation transition of water in spherical pores in equilibrium
      with saturated bulk water.
AB  - Liquid-vapor phase transition of water in spherical pores with various strengths
      of water-surface interaction is studied under conditions of equilibrium with the
      saturated bulk water. The excess chemical potential of bulk liquid water along
      the liquid-vapor coexistence curve was determined by the overlapping distribution
      method. The adsorption and desorption of water in pores were studied by Monte
      Carlo simulations in the grand canonical ensemble in the temperature range T =
      270-580 K with a step 10 K. The well depth U(0) of the water-surface potential
      was varied from ~-0.6 kcal/mol (hydrophobic pore surface) to ~-7.1 kcal/mol
      (hydrophilic pore surface). The diagram showing the areas of the stable,
      metastable, and unstable liquid and vapor phases of confined water in the T -
      U(0) plane has been constructed. Water vapor only exists in pores with U(0) > 
      1.2 kcal/mol, whereas liquid water only exists in pores with U(0) < -2.8
      kcal/mol. The interval DeltaU(0), where both stable and metastable states of
      confined water are possible, shrinks upon heating almost linearly and disappears
      at the hysteresis pore critical temperature T(p)(h). Above T(p)(h), there is a
      particular value U(0)(c) ~ -1.35 kcal/mol that divides the regimes of capillary
      condensation and capillary evaporation up to the pore critical temperature
      T(p)(c). The obtained results can be used for the optimization of porous
      materials for applications that require controlled adsorption and desorption of
      water.

PMID- 21080662
TI  - Synthesis and structure of m-terphenyl thio-, seleno-, and telluroethers.
AB  - Several routes for the synthesis of m-terphenyl thio-, seleno-, and telluroethers
      were investigated. m-Terphenyl iodides react with diphenyl diselenides or
      ditellurides (CsOH.H(2)O, DMSO, 110  degrees C) to give the desired compounds in
      19-84% yield which significantly extends the previously reported such reactions
      because o-benzyne cannot be an intermediate as previously suggested. However, the
      most general synthetic route was that involving reaction of 2,6-diaryl Grignard
      reagents with sulfur, selenium, or tellurium electrophiles. The m-terphenyl thio
      , seleno-, and telluroethers were characterized spectroscopically and, in one
      case, by single-crystal X-ray analysis. Certain of these compounds showed
      atropisomerism and barriers for interconversion of isomers were determined by
      variable-temperature NMR spectroscopy. The barriers for interconverting the syn
      and anti atropisomers increase on going from the analogous S to Se to Te
      compounds. Calculations on this isomerization revealed that the barriers are due
      to rotation about the aryl-aryl bond and that the barriers for rotation about the
      aryl-chalcogen bond are much lower.

PMID- 21080663
TI  - Nonlinear dark-field microscopy.
AB  - Dark-field microscopy is a background-free imaging method that provides high
      sensitivity and a large signal-to-noise ratio. It finds application in nanoscale
      detection, biophysics and biosensing, particle tracking, single molecule
      spectroscopy, X-ray imaging, and failure analysis of materials. In dark-field
      microscopy, the unscattered light path is typically excluded from the angular
      range of signal detection. This restriction reduces the numerical aperture and
      affects the resolution. Here we introduce a nonlinear dark-field scheme that
      overcomes this restriction. Two laser beams of frequencies omega1 and omega2 are
      used to illuminate a sample surface and to generate a purely evanescent field at
      the four-wave mixing (4WM) frequency omega4wm = 2omega1 - omega2. The evanescent
      4WM field scatters at sample features and generates radiation that is detected by
      standard far-field optics. This nonlinear dark-field scheme works with samples of
      any material and is compatible with applications ranging from biological imaging
      to failure analysis.

PMID- 21080664
TI  - Soft nanostructuring of YBCO Josephson junctions by phase separation.
AB  - We have developed a new method to fabricate biepitaxial YBa2 Cu3 O7-delta (YBCO)
      Josephson junctions at the nanoscale, allowing junctions widths down to 100 nm
      and simultaneously avoiding the typical damage in grain boundary interfaces due
      to conventional patterning procedures. By using the competition between the
      superconducting YBCO and the insulating Y2 BaCuO5 phases during film growth, we
      formed nanometer sized grain boundary junctions in the insulating Y2 BaCuO5
      matrix as confirmed by high-resolution transmission electron microscopy.
      Electrical transport measurements give clear indications that we are close to
      probing the intrinsic properties of the grain boundaries.

PMID- 21080665
TI  - Supramolecular self-assembly driven by electrostatic repulsion: The 1D
      aggregation of rubrene pentagons on Au111.
AB  - At present, organic molecules are among the best candidate "building blocks" for
      the construction of self-assembling nanoscale devices based on metal substrates.
      Control of the formation of specific patterns in the submonolayer regime is
      usually achieved by appropriate choice and/or functionalization of the
      adsorbates. The effect of this intervention, though, is limited by the typically
      short-range character of the bonding. We present here a theoretical study on the
      system rubrene/gold to show that substrate-induced molecular charging can instead
      determine the assembly on larger scales. DFT calculations and electrostatic
      considerations are used to discuss the charge transfer at the metal/organic
      interface. This allows rationalization of previous puzzling experimental results
      and, in particular, of the unusual molecular gap broadening upon adsorption
      observed in STS spectra. The self-assembly process is further studied by means of
      classical molecular dynamics simulations. The charged adsorbates are modeled as
      mutually repulsive standing dipoles, with van der Waals interactions intervening
      at short distances. The striking resemblance between the experimental STM images
      and the results of our MD simulations shows that this simple model is able to
      capture the key effects driving the assembly in this system. The competition
      between long-range repulsive interactions and short-range attractive forces leads
      to characteristic and easily recognizable 1D patterns. We suggest that
      experimental evidence of the presence of similar patterns in other metal/organic
      systems can provide crucial information on the electronic level alignment at the
      interface, that is, on the occurrence of charge-transfer processes between metal
      and organic adsorbates.

PMID- 21080666
TI  - Plugging into proteins: poisoning protein function by a hydrophobic nanoparticle.
AB  - Nanoscale particles have become promising materials in many fields, such as
      cancer therapeutics, diagnosis, imaging, drug delivery, catalysis, as well as
      biosensors. In order to stimulate and facilitate these applications, there is an
      urgent need for the understanding of the nanoparticle toxicity and other risks
      involved with these nanoparticles to human health. In this study, we use large
      scale molecular dynamics simulations to study the interaction between several
      proteins (WW domains) and carbon nanotubes (one form of hydrophobic
      nanoparticles). We have found that the carbon nanotube can plug into the
      hydrophobic core of proteins to form stable complexes. This plugging of nanotubes
      disrupts and blocks the active sites of WW domains from binding to the
      corresponding ligands, thus leading to the loss of the original function of the
      proteins. The key to this observation is the hydrophobic interaction between the
      nanoparticle and the hydrophobic residues, particularly tryptophans, in the core
      of the domain. We believe that these findings might provide a novel route to the
      nanoparticle toxicity on the molecular level for the hydrophobic nanoparticles.

PMID- 21080667
TI  - Binding of carboxylic acids by fluorescent pyridyl ureas.
AB  - Fluorescent pyrid-2-yl ureas were prepared by treating halogenated 2
      aminopyridines with hexyl isocyanate, followed by Sonogashira coupling with
      arylacetylenes. The sensors emit light of ~360 nm with quantum yields of 0.05-0.1
      in acetonitrile solution. Addition of strong organic acids (pK(a) < 13 in
      CH(3)CN) shifts the fluorescence band to lower energy, and clean isoemissive
      behavior is observed. Fluorescence response curves (i.e., F/F(0) vs
      [acid](total)) are hyperbolic in shape for CCl(3)COOH and CF(3)COOH, with
      association constants on the order of 10(3) M(-1) for both acids. (1)H NMR
      titrations and DFT analyses indicate that trihaloacetic acids bind in ionized
      form to the receptors. Pyridine protonation disrupts an intramolecular H-bond,
      thereby unfolding an array of ureido NH donors for recognition of the
      corresponding carboxylates. Methanesulfonic acid protonates the sensors, but no
      evidence for conjugate base binding at the urea moiety is found by NMR. An
      isosteric control compound that lacks an integrated pyridine does not undergo
      significant fluorescence changes upon acidification.

PMID- 21080668
TI  - Environmentally responsive particles: from superhydrophobic particle films to
      water-dispersible microspheres.
AB  - We describe the preparation, by precipitation copolymerization, of
      multifunctional divinylbenzene-co-pentafluorostyrene microspheres able to produce
      superhydrophobic surfaces or disperse in aqueous media upon annealing either in
      air or water, respectively. For that purpose, an amphiphilic block copolymer,
      polystyrene-b-poly(acrylic acid), was introduced in the initial feed composed of
      divinylbenzene and 2,3,4,5,6-pentafluorostyrene. As a result, fluorinated
      particles were obtained in which the diblock copolymer was encapsulated during
      the polymerization step. Upon annealing in dry air, the particles are completely
      hydrophobic and form superhydrophobic surfaces. On the contrary, annealing in
      water induces the reorientation of the PAA groups toward the particle interface,
      thus the particles can be dispersed in aqueous media. In addition, the presence
      of carboxylic acid groups at the particle interface permits us to switch the
      surface charge between negative and neutral depending on the environmental pH.

PMID- 21080669
TI  - Controlling the structure of proteins at surfaces.
AB  - With the help of single molecule force spectroscopy and molecular dynamics
      simulations, we determine the surface-induced structure of a single engineered
      spider silk protein. An amyloid like structure is induced in the vicinity of a
      surface with high surface energy and can be prohibited in the presence of a
      hydrophobic surface. The derived molecular energy landscapes highlight the role
      of single silk protein structure for the macroscopic toughness of spider silk.

PMID- 21080670
TI  - Highly enantioselective Rh2(S-DOSP)4-catalyzed cyclopropenation of alkynes with
      styryldiazoacetates.
AB  - Dirhodium tetrakis((S)-N-(dodecylbenzenesulfonyl)prolinate) (Rh2(S-DOSP)4) is an
      effective catalyst for highly enantioselective cyclopropenation reactions between
      terminal alkynes and arylvinyldiazoacetates. The resulting vinylcyclopropenes can
      undergo rhodium-catalyzed regioselective rearrangement to cyclopentadienes.
      Computational studies indicate that the high enantioselectivity of the process is
      governed by the specific orientation of the alkyne during its approach to the
      carbenoid through a relatively late transition state. The specific orientation
      occurs due to the presence of a hydrogen bonding interaction between the alkyne
      hydrogen and a carboxylate ligand on the dirhodium catalyst.

PMID- 21080671
TI  - U.S. EPA regulation of plant-incorporated protectants: assessment of impacts of
      gene flow from pest-resistant plants.
AB  - The U.S. Environmental Protection Agency licenses pesticide-expressing plants
      under the authority of the Federal Insecticide, Fungicide and Rodenticide Act
      (FIFRA). Transgenes and their pesticidal products represent pesticides under
      FIFRA and are referred to as plant-incorporated protectants (PIPs). When sexually
      compatible wild relatives (SCWR) are sympatric with PIP crops, there is a need to
      assess the potential for adverse effects to man and the environment resulting
      from transgene introgression in accord with FIFRA requirements. Genetic
      compatibility, introgression, weediness of SCWR * PIP hybrids, seed dispersal,
      and dormancy, among other parameters, as well as effects on other species
      (herbivores and beneficial insects), all need to be considered as part of the
      risk assessment for experimental use under Section 5 or registration under
      Section 3 of FIFRA. EPA is currently developing data requirements and guidance
      toward addressing potential gene flow impacts from PIPs.

PMID- 21080672
TI  - Epitaxial growth of shape-controlled Bi2Te3-Te heterogeneous nanostructures.
AB  - A one-pot solution process has been devised to synthesize colloidal Bi2Te3-Te
      heterogeneous nanostructures (HNs) that comprise Bi2Te3 nanoplates and Te
      nanorods. By controlling the reaction kinetics, the reaction of TeO3(2-) and
      Bi(3+) in the presence of hydrazine first produces uniform Te nanorods and then
      grows Bi2Te3 nanoplates on the tips and surfaces of these Te nanorods, forming
      various shapes including "nails", "barbells", "syringes", and "accordions". The
      specific topological arrangement realized arises from the peculiar anisotropic
      reactivity of the first formed Te nanorods, whose tips are subsequently exploited
      to seed the heterogeneous nucleation of Bi2Te3 as enabled by the similar crystal
      structure and the small lattice mismatch between Te and Bi2Te3. Three important
      processes, heterogeneous nucleation of Bi2Te3 on the tips and/or surface of Te
      nanorods, homogeneous nucleation of Bi2Te3, and the direct reaction of a Bi
      precursor and Te nanorods to form hollow structures via the Kirkendall Effect,
      occur under various conditions. The manipulation of these processes provides a
      robust means for the fine shape control of Bi2Te3-Te HNs. It is envisioned that
      the tailored synthesis of Bi2Te3-Te HNs may promise unique opportunities for
      producing thermoelectric materials with greatly enhanced performance.

PMID- 21080673
TI  - Mass spectrometry of ligand exchange chelation of the nanoparticle
      [Au25(SCH2CH2C6H5)18]1- by CH3C6H3(SH)2.
AB  - Mass spectrally detected products of ligand exchange reactions of the
      nanoparticle [Au25(SC2H4C6H5)18](1-), (abbrev. Au25(SC2Ph)18), where the dithiol
      is toluene-3,4-dithiol, CH3C6H3(SH)2, include nanoparticles containing both
      doubly (bidentate, or chelating) and singly bonded dithiol. The bidentate binding
      displaces two of the original -SC2Ph ligands, and singly bonded dithiol displaces
      one -SC2Ph ligand, while maintaining, for mass spectrally detected species,
      occupancy of 18 ligation sites. Extended exchange reaction times result in an
      apparent maximum of six chelated dithiolates. In the Au25(SC2Ph)18 nanoparticle,
      six semi-rings of -S(R)-Au-S(R)-Au-S(R)- act as the protecting ligand shell
      surrounding a Au13 core; the chelation is suggested to involve binding of
      dithiolates to adjacent semi-rings, rather than to a single semi-ring. Both high
      resolution ESI and lower resolution MALDI spectra support the product
      assignments. A minor extent of bidentate ligand incorporation is sufficient to
      severely compromise the well-known Au25(SC2Ph)18 UV-vis fine structure and to
      alter its voltammetric pattern, reflecting either associated semi-ring distortion
      and/or decay of the exchange product.

PMID- 21080674
TI  - Polarization-angle-scanning two-dimensional spectroscopy: application to
      dipeptide structure determination.
AB  - Coherent two-dimensional optical spectroscopy based on a heterodyne-detected
      stimulated photon echo measurement technique requires four ultrashort pulses
      whose pulse-to-pulse delay times, wavevectors, and frequencies are experimentally
      controllable variables. In addition, the polarization directions of the four
      radiations can also be arbitrarily adjusted. We show that the polarization-angle
      scanning two-dimensional spectroscopy can be of effective use to selectively
      suppress either all the diagonal peaks or a cross-peak in a given two-dimensional
      spectrum. Theoretical relationships between the transition dipole vectors of a
      given pair of coupled modes or quantum transitions and the polarization angle
      configuration making the corresponding cross-peak vanish are established. Here,
      to shed light into the underlying principles of the polarization-angle-scanning
      two-dimensional spectroscopy, we considered the amide I vibrations of various
      isotope-labeled dipeptide conformers and show that one can selectively suppress a
      cross-peak by properly controlling the polarization angle of a chosen beam among
      them. Once the relative directions of the amide I transition dipole vectors are
      determined using the polarization-angle-scanning technique theoretically proposed
      here, they can serve as a set of constraints for determining structures of model
      peptides. The present work demonstrates that the polarization-controlled two
      dimensional vibrational or electronic spectroscopy can provide invaluable
      information on intricate details of molecular structures.

PMID- 21080675
TI  - Synthesis of a single-molecule L-rhamnose-containing three-component vaccine and
      evaluation of antigenicity in the presence of anti-L-rhamnose antibodies.
AB  - Carbohydrates are generally considered to be poorly immunogenic. Therefore, new
      approaches for enhancing their immunogenicity are important for the development
      of carbohydrates as vaccine components. We hypothesized that conjugation of an l
      rhamnose (Rha) moiety to a carbohydrate antigen would enhance the antigenicity of
      the antigen in mice possessing anti-Rha antibodies via an antibody-dependent
      antigen uptake mechanism. To explore this hypothesis, we synthesized a single
      molecule three-component vaccine containing the GalNAc-O-Thr (Tn) tumor-specific
      antigen, a 20 amino acid helper T-cell epitope (YAF) derived from an outer
      membrane protein of Neisseria meningitides, and a Rha moiety. The vaccine was
      synthesized by automated Fmoc-based solid-phase peptide synthesis and
      deacetylated by brief treatment with NaOMe. Groups of female BALB/c mice were
      immunized and boosted with Rha-ovalbumin (Rha-OVA) formulated with either
      TiterMax Gold or Sigma Adjuvant System for a period of 35 days in order to
      determine optimal conditions for generating anti-Rha titers in mice. Anti-Rha
      antibody titers were >100 fold higher in groups of mice immunized with Rha-OVA
      than in the control groups. Mice producing anti-Rha were challenged with Rha-YAF
      Tn or YAF-Tn. Sera collected from the groups initially immunized with Rha-OVA and
      later challenged with Rha-YAF-Tn showed a 2-fold increase in anti-Tn titer at
      1/100 serum dilution relative to mice not immunized with Rha-OVA. An in vitro T
      cell proliferation study using cells primed with either Rha-YAF-Tn or YAF-Tn was
      done to examine possible differences in antigen uptake and presentation due to
      anti-Rha antibody and chemical modification. Proliferation of T cells was
      stimulated by a 10-fold lower antigen concentration in the presence of Rha
      antibodies. The results strongly suggest that T cells present in the spleen were
      presented with higher concentrations of Rha-YAF-Tn as a result of the presence of
      the anti-Rha antibodies.

PMID- 21080676
TI  - Simultaneous analysis of amino acids and carboxylic acids by capillary
      electrophoresis-mass spectrometry using an acidic electrolyte and uncoated fused
      silica capillary.
AB  - A simple, low-cost capillary electrophoresis-mass spectrometry (CE-MS) method is
      demonstrated for the simultaneous analysis of amino acids and small carboxylic
      acids (glycerate, lactate, fumarate, succinate, malate, tartrate, citrate, iso
      citrate, cis-aconitate, and shikimate). All CE-MS experiments were performed
      using a single uncoated fused-silica capillary and with a single separation
      electrolyte, formic acid. For CE polarity, the CE inlet was set as the anode, and
      the MS side was set as the cathode. By using high-speed sheath gas flow, the
      apparent mobilities of all compounds were sped up; thus, the migration times of
      the carboxylic acids were reduced. In positive ion mode ESI-MS detection, small
      carboxylic acids were detected faintly as m/z = [M + 18](+) or [M + 23](+), after
      protonated molecule detection (m/z = [M + 1](+)) of the amino acids. In negative
      ion mode, all of these small carboxylic acids were detected clearly as
      deprotonated molecules (m/z = [M - 1](-)), after detection of the amino acids. By
      changing the polarity of the MS during CE separation, both amino acids and small
      carboxylic acids were detectable in a single electrophoresis analysis run. With
      this method, the diurnal metabolic changes of pineapple leaves were observed as
      reflecting Crassulacean acid metabolism.

PMID- 21080677
TI  - Influence of sequence on the self-assembly of peptide nanoribbons on silicon
      substrates.
AB  - This work reports the formation of stable nanoassemblies of short pentapeptides
      LKLKL (pepI) and their mutated sequence LKKLL (pepII) obtained from their
      Langmuir-Blodgett films transferred onto hydrophilic and hydrophobic silicon
      substrates. The adsorption and assembly of the LB films of these peptides on
      solid surfaces have been studied by quartz crystal microbalance, surface plasmon
      resonance, and scanning electron microscopy. Both pepI and pepII assemble into
      nanosized ribbons, with diameters around 20-25 nm and lengths greater than 5 MUm
      on hydrophobic surface, and tend to aggregate on hydrophilic surfaces with pepII
      showing twisted structures. Circular dichroic spectra of the films on a
      hydrophobic surface showed formation of a beta-sheet-like structure, while the
      corresponding solution spectra did not show any specific secondary structure. Our
      results demonstrate the formation of a two-dimensional dense array of
      nanoassemblies with either vertical or horizontal patterns from such short
      peptides that may find application in nanotechnology.

PMID- 21080678
TI  - Mechanistic studies on a P450-mediated rearrangement of BMS-690514: conversion of
      a pyrrolotriazine to a hydroxypyridotriazine.
AB  - BMS-690514 ((3R,4R)-4-amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f][1,2,4]
      triazin-5-yl)methyl)-3-piperidinol) is an oral oncologic agent being developed
      for the treatment of patients with advanced nonsmall cell lung cancer and breast
      cancer. The compound is metabolized via multiple metabolic pathways, including
      P450-mediated oxidation at one of the carbons of its pyrrolotriazine group.
      Oxidation at this site results in the formation of two metabolites, M1 and M37.
      Mass spectrometric and NMR analysis revealed that M1 underwent an unusual
      structural change, where the pyrrolotriazine moiety rearranged to yield a
      hydroxypyridotriazine group. In contrast, the structure of the pyrrolotriazine
      moiety remained intact in M37. In vitro experiments with liver microsomes and
      deuterated or tritiated BMS-690514 containing the isotopic label on the carbon
      that underwent oxidation indicated that during the formation of M1, the isotope
      label was retained at the site of hydroxylation, while the label was lost during
      the formation of M37. On the basis of these results, a mechanism for the
      formation of M1 was proposed as follows: BMS-690514 was first oxidized by P450
      enzymes either via epoxidation or an iron-oxo addition pathway to form a
      zwitterionic intermediate. This was followed by opening of the pyrrolotriazine
      ring to form an aldehyde intermediate, which could be partially trapped with
      methoxyamine. The aldehyde intermediate then reacted with the secondary amine of
      the methoxyaniline group in the molecule to form the pyridotriazine moiety of M1.
      This mechanism is consistent with the observed retention of the isotope label in
      M1. Metabolite M37 may be formed either via a common zwitterionic intermediate,
      shared with M1, or through a direct insertion pathway. In in vitro human liver
      microsome incubations, the abundance of M1 was higher than M37, suggesting that
      breaking of the carbon-nitrogen bond to generate the aldehyde intermediate, a
      process similar to N-dealkylation, was a preferred pathway.

PMID- 21080679
TI  - Toward an understanding of the salting-out effects in aqueous ionic liquid
      solutions: vapor-liquid equilibria, liquid-liquid equilibria, volumetric,
      compressibility, and conductivity behavior.
AB  - The action of particular electrolytes in altering the solution properties of
      ionic liquids is well documented, although the origin of this effect is not
      clearly defined. In order to clarify this point, the aim of this work is to
      obtain further evidence about the salting-out effect produced by the addition of
      different salts to aqueous solutions of water miscible ionic liquids by
      evaluating the effect of a large series of salts on the vapor-liquid equilibria,
      liquid-liquid phase diagram, volumetric, compressibility, and conductometric
      properties of ionic liquids 1-alkyl-3-methylimidazolium halide ([C(n)mim][X]). In
      the first part of this work, the experimental measurements of water activity at
      298.15 and 308.15 K for aqueous binary and ternary solutions containing 1-alkyl-3
      methylimidazolium bromide ([Rmim][Br], R = butyl (C(4)), heptyl (C(7)), and octyl
      (C(8))), sodium dihydrogen citrate (NaH(2)Cit), disodium hydrogen citrate
      (Na(2)HCit), and trisodium citrate (Na(3)Cit) are taken using both vapor pressure
      osmometry (VPO) and improved isopiestic methods. The effect of temperature,
      charge on the anion of sodium citrate salts, and alkyl chain length of ionic
      liquids on the vapor-liquid equilibria properties of the investigated systems are
      studied. The constant water activity lines of all the ternary systems show large
      negative deviation from the linear isopiestic relation (Zdanovskii-Stokes
      Robinson rule) derived using the semi-ideal hydration model, and the vapor
      pressure depression for a ternary solution is much larger than the sum of those
      for the corresponding binary solutions with the same molality of the ternary
      solution. The results have been interpreted in terms of the solute-water and
      solute-solute interactions. In the second part of this work, the effects of the
      addition of (NH(4))(3)Cit, K(3)Cit, Na(3)Cit, (NH(4))(2)HPO(4), and
      (NH(4))(3)PO(4) on the liquid-liquid phase diagram, apparent molar volume,
      isentropic compressibility, and conductivity of aqueous solutions containing the
      model ionic liquid 1-butyl-3-methylimidazolium iodide, [C(4)mim][I], are
      investigated at different temperatures. It was found that there is a relation
      between the relative concentration of various salts to form two-phase systems
      with [C(4)mim][I] and apparent molar volume or isentropic compressibility of
      transfer of [C(4)mim][I] from water to aqueous solutions of the investigated
      salts.

PMID- 21080680
TI  - Origin of the low-viscosity of [emim][(FSO2)2N] ionic liquid and its lithium salt
      mixture: experimental and theoretical study of self-diffusion coefficients,
      conductivities, and intermolecular interactions.
AB  - The temperature-dependent viscosity, ionic conductivity, and self-diffusion
      coefficients of an ionic liquid, 1-ethyl-3-methylimidazolium
      bis(fluorosulfonyl)amide ([emim][FSA]), and its Li salt mixture were studied with
      reference to emim bis(trifluoromethyl-sulfonyl)amide ([emim][TFSA]) systems. The
      stabilization energies for the formation of the FSA(-) complexes with emim(+) and
      Li(+) were calculated by the MP2/6-311G** level ab initio method. The
      stabilization energies calculated for the FSA(-) complexes with emim(+) and Li(+)
      (-77.0 and -134.3 kcal/mol) were smaller than those for the corresponding TFSA(-)
      complexes (-78.8 and -137.2 kcal/mol). The weaker electrostatic and induction
      interactions are the causes of the smaller interaction energies for the FSA(-)
      complexes. The weaker interaction between the FSA(-) and emim(+) can be one of
      the causes of the lower viscosity of the [emim][FSA] ionic liquid compared with
      that of the [emim][TFSA] ionic liquid. The weaker interaction between the FSA(-)
      and Li(+) compared with that between the TFSA(-) and Li(+) explains the fact that
      the addition of Li salt to the [emim][FSA] ionic liquid induces a little increase
      of the viscosity and a little decrease of the ionic conductivity and self
      diffusion coefficients of ions. The FSA(-) in the Li[FSA] complex prefers the cis
      form due to the stronger attraction and smaller deformation energy of the cis
      FSA(-) compared with the trans-FSA(-).

PMID- 21080681
TI  - Large-scale arrays of single-layer graphene resonators.
AB  - We fabricated large arrays of suspended, single-layer graphene membrane
      resonators using chemical vapor deposition (CVD) growth followed by patterning
      and transfer. We measure the resonators using both optical and electrical
      actuation and detection techniques. We find that the resonators can be modeled as
      flat membranes under tension, and that clamping the membranes on all sides
      improves agreement with our model and reduces the variation in frequency between
      identical resonators. The resonance frequency is tunable with both electrostatic
      gate voltage and temperature, and quality factors improve dramatically with
      cooling, reaching values up to 9000 at 10 K. These measurements show that it is
      possible to produce large arrays of CVD-grown graphene resonators with
      reproducible properties and the same excellent electrical and mechanical
      properties previously reported for exfoliated graphene. 

PMID- 21080682
TI  - Three-dimensional self-assembly of graphene oxide and DNA into multifunctional
      hydrogels.
AB  - Graphene and its functionalized derivatives are unique and versatile building
      blocks for self-assembly to fabricate graphene-based functional materials with
      hierarchical microstructures. Here we report a strategy for three-dimensional
      self-assembly of graphene oxide sheets and DNA to form multifunctional hydrogels.
      The hydrogels possess high mechanical strength, environmental stability, and dye
      loading capacity, and a exhibit self-healing property. This study provides a new
      insight for the assembly of functionalized graphene with other building blocks,
      especially biomolecules, which will help rational design and preparation of
      hierarchical graphene-based materials.

PMID- 21080683
TI  - Characterization of the estradiol-binding site structure of human pancreas
      specific protein disulfide isomerase: indispensable role of the hydrogen bond
      between His278 and the estradiol 3-hydroxyl group.
AB  - Estradiol (E(2)), a female sex hormone, has important biological functions. Human
      pancreas-specific protein disulfide isomerase (PDIp), a protein folding catalyst,
      was recently found to be able to bind E(2). Here we report the characterization
      of its E(2)-binding site by using biochemical methods coupled with molecular
      modeling tools. Analysis of various truncated PDIp proteins showed that the b-b'
      fragment contains an intact E(2)-binding site that has the same binding affinity
      as the full-length PDIp protein, with apparent K(d) values of approximately 170
      nM. Computational modeling and docking analyses revealed that the E(2)-binding
      site in the b-b' fragment is located in a hydrophobic pocket composed mainly of
      the b' domain and partially of the b domain. The hydrogen bond, formed between
      the 3-hydroxyl group of E(2) (donor) and PDIp's His278 (acceptor), is
      indispensable for its binding. By contrast, the 17beta-hydroxyl group of E(2) is
      of negligible importance for E(2) binding. This binding model was jointly
      confirmed by a series of experiments, such as selective mutation of the binding
      site amino acid residues and selective modification of the ligand structures.

PMID- 21080684
TI  - Quantum vibrational analysis of hydrated ions using an ab initio potential.
AB  - We present full-dimensional potential energy surfaces (PESs) for hydrated
      chloride based on the sum of ab initio (H(2)O)Cl(-), (H(2)O)(2), and (H(2)O)(3)
      potentials. The PESs are shown to predict minima and corresponding harmonic
      frequencies accurately on the basis of comparisons with previous and new ab
      initio calculations for (H(2)O)(2)Cl(-), (H(2)O)(3)Cl(-), and (H(2)O)(4)Cl(-). An
      estimate of the effect of the 3-body water interaction is made using a simple 3
      body water potential that was recently fit to tens of thousands of ab initio 3
      body energies. Anharmonic, coupled vibrational calculations are presented for
      these clusters, using the "local monomer model" for the high frequency
      intramolecular modes. This model is tested against previous "exact" calculations
      for (H(2)O)Cl(-). Radial distribution functions at 0 K obtained from quantum zero
      point wave functions are also presented for the (H(2)O)(2)Cl(-) and (H(2)O)(3)Cl(
      ) clusters.

PMID- 21080685
TI  - Optical properties of individual silicon nanowires for photonic devices.
AB  - Silicon is a high refractive index material. Consequently, silicon nanowires
      (SiNWs) with diameters on the order of the wavelengths of visible light show
      strong resonant field enhancement of the incident light, so this type of
      nanomaterial is a good candidate for all kinds of photonic devices. Surprisingly
      enough, a thorough experimental and theoretical analysis of both the polarization
      dependence of the absorption and the scattering behavior of individual SiNWs
      under defined illumination has not been presented yet. Here, the present paper
      will contribute by showing optical properties such as scattering and absorption
      of individual SiNWs experimentally in an optical microscope using bright- and
      dark-field illumination modes as well as in analytical Mie calculations.
      Experimental and calculation results are in good agreement, and both reveal a
      strong correlation of the optical properties of individual SiNWs to their
      diameters. This finding supports the notion that SiNWs can be used in photonic
      applications such as for photovoltaics or optical sensors.

PMID- 21080686
TI  - Practical synthesis of functionalized 1,5-disubstituted 1,2,4-triazole
      derivatives.
AB  - A general approach for the synthesis of 1,5-disubstituted-1,2,4-triazole
      compounds is described. A series of new oxamide-derived amidine reagents can be
      accessed in excellent yield with minimal purification necessary. Typically, these
      amidine reagents are stable crystalline solids and in certain cases were found to
      exist in a cyclic form as determined by NMR spectroscopy. Under optimized
      conditions, the direct reaction of these prepared reagents with various hydrazine
      hydrochloride salts efficiently generates the target triazoles. Both aromatic and
      aliphatic hydrazines react readily with the amidine reagents under very mild
      reaction conditions, delivering desired 1,5-disubstituted-1,2,4-triazole
      derivatives in good yields.

PMID- 21080687
TI  - Oxidative cleavage of alkenes using an in situ generated iodonium ion with oxone
      as a terminal oxidant.
AB  - A facile and operationally convenient catalytic procedure for oxidative cleavage
      of alkenes is described. In situ formed [hydroxy(4-carboxyphenyl)iodonium]ion, 2,
      from the oxidation of 4-iodobenzoic acid, 1, has been shown to facilitate the
      cleavage of a variety of alkenes in presence of Oxone as a co-oxidant.
      Optimization of the reaction conditions using 1-phenyl-1-cyclohexene, 3, and the
      competitive oxidative cleavage of different substrates using the optimized
      conditions has uncovered important mechanistic details of the reaction.

PMID- 21080688
TI  - Complexation of 2,6-bis(acylamino)pyridines with dipyridin-2-ylamine and 4,4
      dimethylpiperidine-2,6-dione.
AB  - Intermolecular hydrogen bonds between 2,6-bis(acylamino)pyridines and dipyridin-2
      ylamine as well as 4,4-dimethylpiperidine-2,6-dione are responsible for
      relatively strong interactions between these species. Association has been found
      to be significantly affected by the size of acyl substituent (chemical shift of
      the NH proton was used as the main probe in determination of the association
      constants). Calculations at the DFT level of theory are in line with the
      experimentally observed results. Calculated energies of the interactions between
      the complex congeners also show the size of the substituent to affect the
      association. Conformational changes in the dipyridin-2-ylamine molecule are shown
      to adapt a geometry suitable for formation of efficient hydrogen bonding.

PMID- 21080689
TI  - Prediction of active site cleft using support vector machines.
AB  - Computational tools are available today for the detection and delineation of the
      clefts and cavities in protein 3D structure and ranking them on the basis of
      probable binding site clefts. There is a need to improve the ranking of clefts
      and accuracy of predicting catalytic site clefts. Our results show that the
      distance of the clefts from protein centroid and sequence entropy of the lining
      residues, when used in conjunction with the volume, are valuable descriptors for
      predicting the catalytic site. We have applied the SVM approach for recognizing
      and ranking the active site clefts and tested its performance using different
      combinations of attributes. In both the ligand-bound and the unbound forms of
      structures, our method correctly predicts the active site clefts in 73% of cases
      at rank one. If we consider the results at rank 3 (i.e., the correct solution is
      among one of the top three solutions), the correctly predicted cases are 94% and
      90% for the bound and the unbound forms of structures, respectively. Our approach
      improves the ranking of binding site clefts in comparison with CASTp and is
      comparable to other existing methods like Fpocket. Although the data set for
      training the SVM approach is rather small in size, the results are encouraging
      for the method to be used as complementary to other existing tools.

PMID- 21080690
TI  - Effect of transition state aromaticity and antiaromaticity on intrinsic barriers
      of proton transfers in aromatic and antiaromatic heterocyclic systems; an ab
      initio study.
AB  - An ab initio study of two series of carbon-to-carbon proton transfer reactions is
      reported. The first series refers to the heterocyclic C(4)H(5)X(+)/C(4)H(4)X (X =
      CH(-), NH, S, O, PH, CH(2), AlH, BH) systems, and the second to the linear
      [Formula: see text] (X = CH(-), NH, S, PH, O, CH(2), AlH, BH) reference systems .
      The major objective of this study was to examine to what degree the aromaticity
      of C(4)H(4)X (X = CH(-), NH, S, O, PH) and the antiaromaticity of C(4)H(4)X (X =
      AlH, BH) is expressed at the transition state of the proton transfer and how this
      affects the respective intrinsic barriers. From the differences in the barriers
      between a given cyclic system and the corresponding linear reference system ,
      DeltaDeltaH(++) = DeltaH(++)(cyclic) - DeltaH(++)(linear), it was inferred that
      in the cyclic systems both aromaticity and antiaromaticity lower
      DeltaH(++)(cyclic). This conclusion was based on the assumption that the factors
      not associated with aromaticity or antiaromaticity such as resonance, inductive
      and polarizability effects in the protonated species, and charge delocalization
      occurring along the reaction coordinate affect DeltaH(++) for the cyclic and
      linear systems in a similar way and hence offset each other in DeltaDeltaH(++).
      The extent by which DeltaH(++)(cyclic) is lowered in the aromatic systems
      correlates quite well with the degree of aromaticity of C(4)H(4)X as measured by
      aromatic stabilization energies as well as the NICS(1) values of the respective
      C(4)H(4)X. According to the rules of the principle of nonperfect synchronization
      (PNS), these results imply a disproportionately large degree of aromaticity at
      the transition state for the aromatic systems and a disproportionately small
      degree of transition state antiaromaticity for the antiaromatic systems. These
      conclusions are consistent with the changes in the NICS(1) values along the
      reaction coordinate. Other points discussed in the paper include the complex
      interplay of resonance, inductive, and polarizability effects, along with
      aromaticity and antiaromaticity on the proton affinities of C(4)H(4)X.

PMID- 21080691
TI  - Studies directed toward the synthesis of hamigeran B: a catalytic oxidative
      cyclization.
AB  - An approach to the synthesis of hamigeran B is described. Key steps include a
      Tius-Nazarov cyclization and a palladium-catalyzed oxidative cyclization of an
      alpha-hydroxyenone.

PMID- 21080692
TI  - Ligand-steered modeling and docking: A benchmarking study in class A G-protein
      coupled receptors.
AB  - Class A G-protein-coupled receptors (GPCRs) are among the most important targets
      for drug discovery. However, a large set of experimental structures, essential
      for a structure-based approach, will likely remain unavailable in the near
      future. Thus, there is an actual need for modeling tools to characterize
      satisfactorily at least the binding site of these receptors. Using experimentally
      solved GPCRs, we have enhanced and validated the ligand-steered homology method
      through cross-modeling and investigated the performance of the thus generated
      models in docking-based screening. The ligand-steered modeling method uses
      information about existing ligands to optimize the binding site by accounting for
      protein flexibility. We found that our method is able to generate quality models
      of GPCRs by using one structural template. These models perform better than
      templates, crude homology models, and random selection in small-scale high
      throughput docking. Better quality models typically exhibit higher enrichment in
      docking exercises. Moreover, they were found to be reliable for selectivity
      prediction. Our results support the fact that the ligand-steered homology
      modeling method can successfully characterize pharmacologically relevant sites
      through a full flexible ligand-flexible receptor procedure.

PMID- 21080694
TI  - Influence of hydrogen bonding on hydrogen-atom abstraction reactions of
      dehydropyridinium cations in the gas phase.
AB  - The reactions of several substituted, positively charged dehydropyridinium
      cations with cyclohexane, methanol, and tetrahydrofuran have been examined in a
      Fourier-transform ion cyclotron resonance mass spectrometer. All of the charged
      monoradicals react with the neutral reagents exclusively via hydrogen atom
      abstraction. For cyclohexane, there is a good correlation between the reaction
      efficiencies and the calculated electron affinities at the radical sites; that
      is, the greater the electron affinity of the charged monoradical at the radical
      site, the faster the reaction. The reaction efficiencies with methanol and
      tetrahydrofuran, however, do not correlate with the calculated electron
      affinities. Density functional theory (DFT) calculations indicate that for these
      reagents a stabilizing hydrogen bonding interaction exists in the hydrogen atom
      abstraction transition states for some of the charged monoradicals but not for
      others. At both the MPW1K and G3MP2B3 levels of theory, there is a good
      correlation between the calculated activation enthalpies and the observed
      reaction efficiencies, although the G3MP2B3 method provides a slightly better
      correlation than the MPW1K method. The extent of enhancement in the reaction
      efficiencies caused by the hydrogen bonding interactions parallels the calculated
      hydrogen bond lengths in the transition states.

PMID- 21080695
TI  - A "push-pull" mechanism for heterolytic o-o bond cleavage in hydroperoxo
      manganese porphyrins.
AB  - A water-soluble manganese porphyrin, 5,10,15,20-tetrakis-(1,3-dimethylimidazolium
      2-yl)porphyrinatomanganese(III) (Mn(III)TDMImP) is shown to react with H(2)O(2)
      to generate a relatively stable dioxomanganese(V) porphyrin complex (a compound I
      analog). Stopped-flow kinetic studies revealed Michaelis Menton-type saturation
      kinetics for H(2)O(2). The visible spectrum of a compound 0 type intermediate,
      assigned as Mn(III)(OH)(OOH)TDMImP, can be directly observed under saturating
      H(2)O(2) conditions (Soret band at 428 nm and Q bands at 545 and 578 nm). The
      rate-determining O-O heterolysis step was found to have a very small activation
      enthalpy (DeltaH(?) = 4.2 +/- 0.2 kcal mol(-1)) and a large, negative activation
      entropy (DeltaS(?) = -36 +/- 1 cal mol(-1) K(-1)). The O-O bond cleavage reaction
      was pH independent at 8.8 < pH < 10.4 with a first-order rate constant of 66 +/-
      12 s(-1). These observations indicate that the O-O bond in Mn(III)(OH)(OOH)TDMImP
      is cleaved via a concerted "push-pull" mechanism. In the transition state, the
      axial (proximal) (-)OH is partially deprotonated ("push"), while the terminal
      oxygen in (-)OOH is partially protonated ("pull") as a water molecule is released
      to the medium. This mechanism is reminiscent of O-O bond cleavage in heme
      enzymes, such as peroxidases and cytochrome P450, and similar to the fast,
      reversible O-Br bond breaking and forming reaction mediated by similar manganese
      porphyrins. The small enthalpy of activation suggests that this O-O bond cleavage
      could also be made reversible.

PMID- 21080693
TI  - Mass spectrometry mapping of epidermal growth factor receptor phosphorylation
      related to oncogenic mutations and tyrosine kinase inhibitor sensitivity.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in cancer by
      activating downstream signals important in growth and survival. Inhibitors of
      EGFR are frequently selected as treatment for cancer including lung cancer. We
      performed an unbiased and comprehensive search for EGFR phosphorylation events
      related to somatic activating mutations and EGFR inhibitor (erlotinib)
      sensitivity. EGFR immunoprecipitation combined with high resolution liquid
      chromatography-mass spectrometry and label free quantitation characterized EGFR
      phosphorylation. Thirty (30) phosphorylation sites were identified including 12
      tyrosine (pY), 12 serine (pS), and 6 threonine (pT). Site-specific
      phosphorylation was monitored by comparing ion signals from the corresponding
      unmodified peptide. Phosphorylation sites related to activating mutations in EGFR
      as well as sensitivity to erlotinib were identified using 31 lung cancer cell
      lines. We identified three sites (pY1092, pY1110, pY1172) correlated with
      activating mutations and three sites (pY1110, pY1172, pY1197) correlated with
      erlotinib sensitivity. Five sites (pT693, pY1092, pY1110, pY1172, and pY1197)
      were inhibited by erlotinib in concentration-dependent manner. Erlotinib
      sensitivity was confirmed using liquid chromatography coupled to multiple
      reaction monitoring (LC-MRM) and quantitative Western blotting. This LC-MS/MS
      strategy can quantitatively assess site-specific EGFR phosphorylation and can
      identify relationships between somatic mutations or drug sensitivity and protein
      phosphorylation.

PMID- 21080696
TI  - Enantioselective conjugate addition of oximes to trisubstituted beta
      nitroacrylates: an organocatalytic approach to beta(2,2)-amino acid derivatives.
AB  - A highly enantioselective organocatalytic intermolecular conjugate addition of
      oximes to beta-nitroacrylates has been developed. The highly functionalized
      adducts obtained are valuable precursors for asymmetric synthesis, as
      demonstrated by the synthesis of beta(2,2)-amino acids and oxazolidin-2-ones.

PMID- 21080697
TI  - Chaos induction using a reference model assisted control.
AB  - A stable period two orbit in the parametric vicinity of a chaotic attractor is
      prevented from being reached, via the exclusion of trajectories from its near
      vicinity using a reference model based control strategy. This results in the
      inception of sustained chaotic dynamics. The reference model control strategy
      includes a predictive term enabling delimitation of precluded zones for the
      system dynamics. This technique for promotion of chaotic behavior is illustrated
      by using an experimental electrochemical cell involving the potentiostatic
      electro-dissolution of copper in phosphoric acid.

PMID- 21080698
TI  - Tween 80-sodium deoxycholate mixed micelles: structural characterization and
      application in doxorubicin delivery.
AB  - The objective of the present investigation is to develop and characterize anionic
      mixed micelles of two biocompatible surfactants, Tween 80 (T-80) and sodium
      deoxycholate (NaDC), and evaluate their potential in the delivery of doxorubicin
      hydrochloride (DOX), a cationic anticancer drug. The mixed micelles were
      characterized for their microstructure, intermicellar interactions, and
      doxorubicin binding ability by dynamic light scattering, small angle neutron
      scattering (SANS), viscosity, and optical absorption measurements. Salt-induced
      growth of the mixed micelles at different compositions suggests that both
      electrostatic interaction of the anionic bile salts and steric repulsion of the
      ethylene oxide groups in nonionic components are affected by the presence of
      electrolytes. Addition of bile salt molecules to T-80 micelles suppresses the
      salt-induced growth of nonionic T-80 micelles. SANS studies indicate that bile
      salt micelles are prolate ellipsoidal in shape, and the addition of T-80
      transforms them toward a spherical shape. The anionic bile salt can successfully
      bind to the cationic drug doxorubicin. The in vitro cytotoxicity studies in
      various cancer cell lines revealed that DOX-loaded micelles have greater in vitro
      anticancer activity as compared to DOX solution, indicating their potential in
      pharmaceutical applications.

PMID- 21080699
TI  - Tuning the polylactide hydrolysis rate by plasticizer architecture and
      hydrophilicity without introducing new migrants.
AB  - The possibility to tune the hydrolytic degradation rate of polylactide by
      plasticizer architecture and hydrophilicity without introduction of new
      degradation products was investigated by subjecting polylactide with cyclic
      oligolactide and linear oligolactic acid additives to hydrolytic degradation at
      37 and 60  degrees C for up to 39 weeks. The more hydrophilic oligolactic acid
      plasticizer led to larger water uptake and rapid migration of plasticizer from
      the films into the aging water. This resulted in a porous material more
      susceptible to further hydrolysis. During hydrolysis at 37  degrees C the mass
      loss was generally 10-20% higher for the material containing linear oligolactic
      acid plasticizers. The hydrolysis accelerating effect of the linear oligolactic
      acid is probably counteracted by the higher degree of crystallinity in the films
      containing oligolactic acid additives. The degradation process was monitored by
      measurements of mass loss, water uptake, molar mass changes, material composition
      changes, surface changes, and thermal properties. The water-soluble degradation
      products were analyzed by following pH changes and identified by electrospray
      ionization-mass spectrometry (ESI-MS). The time frame for formation of water
      soluble products was influenced by the architecture and hydrophilicity of the
      plasticizer. Furthermore, the advantage with oligolactide and oligolactic acid
      plasticizers was clearly demonstrated as they do not introduce any new migrants
      into the degradation product patterns.

PMID- 21080700
TI  - Sorption efficiency of chitosan nanofibers toward metal ions at low
      concentrations.
AB  - Chitosan fibers showing narrow diameter distribution with a mean of 42 nm were
      produced by electrospinning and utilized for the sorption of Fe(III), Cu(II),
      Ag(I), and Cd(II) ions from aqueous solutions. The ion concentrations in the
      supernatant solutions were determined using inductively coupled plasma-mass
      spectrometry (ICP-MS). The filtration efficiency of the fibers toward these ions
      was studied by both batch and microcolumn methods. High efficiency in sorption of
      the metal ions was obtained in the both methods. The effects of sorbent amount
      (0.10-0.50 mg), shaking time (15-120 min), initial metal ion concentration (10.0
      1000.0 MUg.L(-1)), and temperature (25 and 50  degrees C) on the extent of
      sorption were examined. The sorbent amount did not significantly alter the
      efficiency of sorption; however, shaking time, temperature, and metal ion
      concentration were found to have a strong influence on sorption. By virtue of its
      mechanical integrity, the applicability of the chitosan mat in solid phase
      extraction under continuous flow looks promising.

PMID- 21080702
TI  - Interactions between antimalarial indolone-N-oxide derivatives and human serum
      albumin.
AB  - The binding affinity of human serum albumin (HSA) to three antimalarial indolone
      N-oxide derivatives, INODs, was investigated under simulated physiological
      conditions using fluorescence spectroscopy in combination with UV-vis absorption
      and circular dichroism (CD) spectroscopy. Analysis of fluorescence quenching data
      of HSA by these compounds at different temperatures using Stern-Volmer and
      Lineweaver-Burk methods revealed the formation of a ground state indolone-HSA
      complex with binding affinities of the order 10(4) M(-1). The thermodynamic
      parameters DeltaG, DeltaH, and DeltaS, calculated at different temperatures,
      indicated that the binding reaction was endothermic and hydrophobic interactions
      play a major role in this association. The conformational changes of HSA were
      investigated qualitatively using synchronous fluorescence and quantitatively
      using CD. Site marker competitive experiments showed that the binding process
      took place primarily at site I (subdomain IIA) of HSA. The number of binding
      sites and the apparent binding constants were also studied in the presence of
      different ions.

PMID- 21080701
TI  - Bacterial chemotaxis along vapor-phase gradients of naphthalene.
AB  - The role of bacterial growth and translocation for the bioremediation of organic
      contaminants in the vadose zone is poorly understood. Whereas air-filled pores
      restrict the mobility of bacteria, diffusion of volatile organic compounds in air
      is more efficient than in water. Past research, however, has focused on
      chemotactic swimming of bacteria along gradients of water-dissolved chemicals. In
      this study we tested if and to what extent Pseudomonas putida PpG7 (NAH7)
      chemotactically reacts to vapor-phase gradients forming above their swimming
      medium by the volatilization from a spot source of solid naphthalene. The
      development of an aqueous naphthalene gradient by air-water partitioning was
      largely suppressed by means of activated carbon in the agar. Surprisingly, strain
      PpG7 was repelled by vapor-phase naphthalene although the steady state gaseous
      concentrations were 50-100 times lower than the aqueous concentrations that
      result in positive chemotaxis of the same strain. It is thus assumed that the
      efficient gas-phase diffusion resulting in a steady, and possibly toxic,
      naphthalene flux to the cells controlled the chemotactic reaction rather than the
      concentration to which the cells were exposed. To our knowledge this is the first
      demonstration of apparent chemotactic behavior of bacteria in response to vapor
      phase effector gradients.

PMID- 21080704
TI  - Hysteretic spin and charge delocalization in a phenalenyl-based molecular
      conductor.
AB  - We have investigated the solid-state electronic structure and properties of a
      phenalenyl-based butyl-substituted neutral radical, 3, that shows a hysteretic
      phase transition just above room temperature. We quantitatively analyzed the
      electron density distribution of this radical throughout both branches of the
      hysteretic phase transition using solid-state X-ray structures and found two
      distinct electronic states in the hysteresis loop that accompanies the phase
      transition. The bistability of the two electronic states was observed through a
      number of measurements, including IR transmittance spectra of single crystals in
      the vicinity of the phase transition. By comparing the changes in the crystal
      structures of 3 and the related ethyl-substituted radical 1 (which exhibits no
      hysteresis) at various temperatures, we show that the change in the interplanar
      pi-pi distance within dimers is the most important structural parameter in
      determining the physical properties of the radicals. The large change in the C
      H...pi interaction in 3 occurs in concert with the spin redistribution during the
      phase transition, but these factors are not responsible for the hysteresis
      effect. We suggest that the presence of a high-temperature state inside the
      hysteretic loop during the cooling cycle is due to thermodynamic stability, while
      the existence of the low-temperature state during the heating cycle is due to the
      presence of a large energy barrier between the two states (estimated to be
      greater than 100 kJ/mol) that results from the large-amplitude motion of the
      phenalenyl rings and the associated lattice reorganization energy that is
      required at the phase transition.

PMID- 21080703
TI  - A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent
      protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor
      xenografts following oral administration.
AB  - Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation
      of cell proliferation, apoptosis, and gene expression. Abnormalities in CDK
      activity and regulation are common features of cancer, making CDK family members
      attractive targets for the development of anticancer drugs. Here, we report the
      identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a
      selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and
      CDK9 (IC50= 3, 30, 30, 250, and 90 nmol/L, respectively). Cell-based studies
      showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA
      polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and
      cell cycle block in the S and G2/M phases. Consistent with these findings, 4k
      demonstrated potent antiproliferative activity in 60 cancer cell lines tested
      (mean GI50= 280 nmol/L). Pharmacokinetic studies showed that 4k is orally
      bioavailable, with an elimination half-life of 178 min following oral dosing in
      mice. When administered at a concentration of 25 mg/kg orally, 4k inhibited human
      tumor xenografts and suppressed CDK substrate phosphorylation. These findings
      identify 4k as a novel, potent CDK selective inhibitor with potential for oral
      delivery in cancer patients.

PMID- 21080705
TI  - How does the synthesis temperature impact hybrid organic-inorganic molybdate
      material design?
AB  - We investigate the reactivity of MoO(4)(2-) toward six organoammonium cations
      (+)(Me(3-x)H(x)N)(CH(2))(2)(NH(y)Me(3-y))(+) (x, y = 1-3) at different synthesis
      temperatures ranging from 70 to 180  degrees C. A total of 16 hybrid organic
      inorganic materials have been synthesized at an initial pH of 2, via ambient
      pressure and hydrothermal routes, namely, (H(2)en)[Mo(3)O(10)].H(2)O (1),
      (H(2)en)[Mo(3)O(10)] (2), (H(2)en)[Mo(5)O(16)] (3),
      (H(2)MED)(2)[Mo(8)O(26)].2H(2)O (4), (H(2)MED)[Mo(5)O(16)] (5), (N,N
      H(2)DMED)(2)[Mo(8)O(26)].2H(2)O (6), (N,N-H(2)DMED)(2)[Mo(8)O(26)].2H(2)O (7),
      (N,N'-H(2)DMED)(2)[Mo(8)O(26)] (8), (N,N'-H(2)DMED)[Mo(5)O(16)] (9),
      (H(2)TriMED)(2)[Mo(8)O(26)].4H(2)O (10), (H(2)TriMED)(2)[Mo(8)O(26)].2H(2)O (11),
      (H(2)TriMED)[Mo(7)O(22)] (12), (H(2)TMED)(2)[Mo(8)O(26)].2H(2)O (13),
      (H(2)TMED)(2)[Mo(8)O(26)] (14), (H(2)TMED)(2)[Mo(8)O(26)] (15), and
      (H(2)TMED)[Mo(7)O(22)] (16). All of these compounds contain different
      polyoxomolybdate (Mo-POM) blocks, i.e., discrete beta-[Mo(8)O(26)](4-) blocks in
      6, 10, 13, 14, (1)/(infinity)[Mo(3)O(10)](2-), and (1)/(infinity)[Mo(8)O(26)](4-)
      polymeric chains in 1, 2, 4, 7, 8, and 15, respectively, and
      (2)/(infinity)[Mo(5)O(16)](2-) and (2)/(infinity)[Mo(7)O(22)](2-) layers in 3, 5,
      9, 12, and 16, respectively. The structures of 5, 9, and 14 have been resolved by
      single-crystal X-ray analyses. The characterization of the different Mo-POM
      blocks in 1-16 by Fourier transform Raman spectroscopy is reported. The impact of
      the synthesis temperature on both the composition and topology of the Mo-POM
      blocks is highlighted.

PMID- 21080706
TI  - Self-assembly of heptameric nanoparticles derived from tag-functionalized phi29
      connectors.
AB  - The structure of an induced macromolecular assembly was characterized and found
      to consist of an ordered heptameric arrangement of recombinant phi29 gp10
      connector molecules. Insertion of an N-terminal Strep-II/His(6) tag to the
      connectors led to the spontaneous formation of large nanoparticles that were
      distinct from free, wild-type phi29 connectors in both size and symmetry
      elements. The determination of single-molecule tomograms and image-averaged
      reconstructions allowed for the stoichiometric and topological characterization
      of the ordered assemblage, revealing that the nanoparticle is composed of five
      equatorial connectors arranged with pseudo-5-fold rotational symmetry, capped on
      its ends by two polar connectors. Additionally, all seven connectors are oriented
      with their narrower N-terminal necks into the nanoparticle core and wider C
      terminal ends out toward the nanoparticle surface, a geometric arrangement
      accommodated by the shape complementarity of the conical connector profiles. A
      significant amount of conformational heterogeneity was detected, ranging from
      changes in overall nanoparticle diameter, to tilting of individual connectors, to
      variations in connector stoichiometry. Nevertheless, a stable, heptameric
      nanoparticle was resolved, revealing the significant potential of guided, peptide
      mediated supramolecular self-assembly. With this construct, we anticipate the
      further design of variable N-terminal tags to allow for the generation of
      nanoparticles with tailored connector stoichiometry and topological arrangements.
      By modifying the surface-exposed C-terminal ends with application-appropriate
      moieties, the consistent structure and compact nature of these nanoparticles may
      prove beneficial in nanotechnological and nanomedical approaches.

PMID- 21080707
TI  - Highly enantioselective alkynylation of trifluoropyruvate with alkynylsilanes
      catalyzed by the BINAP-Pd complex: access to alpha-trifluoromethyl-substituted
      tertiary alcohols.
AB  - A highly enantioselective alkynylation catalyzed by the dicationic (S)-BINAP-Pd
      complex with a variety of alkynylsilanes and trifluoropyruvate is described. The
      catalytic reaction is applicable to highly enantioselective addition of polyyne
      to trifluoropyruvate to construct alpha-trifluoromethyl-substituted tertiary
      alcohols as enantiomerically enriched forms. The alkynyl products can be
      converted into a chiral allene bearing a trifluoromethyl group.

PMID- 21080708
TI  - Exfoliation and chemical modification using microwave irradiation affording
      highly functionalized graphene.
AB  - Efficient exfoliation of graphite flakes by sonicating them in benzylamine was
      accomplished, affording stable suspensions of few-layers graphene. The latter
      were chemically modified following the Bingel reaction conditions, with the aid
      of microwave irradiation, producing highly functionalized graphene-based hybrid
      materials. The resulting hybrid materials, possessing cyclopropanated malonate
      units covalently grafted onto the graphene skeleton, formed stable suspensions
      for several days in a variety of organic solvents and were characterized by
      diverse and complementary spectroscopic, thermal, gravimetric, and high
      resolution electron microscopy techniques. When a malonate derivative, bearing
      the electro-active extended tetrathiafulvalene (exTTF) moiety, was synthesized
      and used for the functionalization of graphene, energy dispersive X-ray (EDX)
      analysis verified the presence of sulfur in the corresponding graphene-based
      hybrid material. Moreover, the redox potentials of the exTTF-graphene hybrid
      material were determined by electrochemistry, while the formation of a radical
      ion pair that includes one-electron oxidation of exTTF and one-electron reduction
      of graphene was suggested with the energy gap of (graphene)(*-)-(exTTF)(*+) being
      calculated as 1.23 eV.

PMID- 21080709
TI  - NHC-catalyzed intramolecular redox amidation for the synthesis of functionalized
      lactams.
AB  - A very efficient NHC-catalyzed lactamization reaction is reported. For most
      cases, the ring expansion reaction proceeds to cleanly furnish five- and six
      membered N-Ts and N-Bn lactams, without the need for further purification.
      Evidence is presented suggesting a dual role for the stoichiometric base: (1)
      deprotonation of the triazolium precatalyst and (2) activation of the nitrogen
      leaving group through hydrogen bonding.

PMID- 21080710
TI  - Electronic structure and spectro-structural correlations of Fe(III)Zn(II)
      biomimetics for purple acid phosphatases: relevance to DNA cleavage and cytotoxic
      activity.
AB  - Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a
      dinuclear Fe(III)M(II) center (M(II) = Fe, Mn, Zn) in the active site and are
      able to catalyze the hydrolysis of a variety of phosphoric acid esters. The
      dinuclear complex [(H(2)O)Fe(III)(MU-OH)Zn(II)(L-H)](ClO(4))(2) (2) with the
      ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N'-(2-pyridylmethyl)(2
      hydroxybenzyl) aminomethyl]phenol (H(2)L-H) has recently been prepared and is
      found to closely mimic the coordination environment of the Fe(III)Zn(II) active
      site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129,
      7486). The biomimetic shows significant catalytic activity in hydrolytic
      reactions. By using a variety of structural, spectroscopic, and computational
      techniques the electronic structure of the Fe(III) center of this biomimetic
      complex was determined. In the solid state the electronic ground state reflects
      the rhombically distorted Fe(III)N(2)O(4) octahedron with a dominant tetragonal
      compression aligned along the MU-OH-Fe-O(phenolate) direction. To probe the role
      of the Fe-O(phenolate) bond, the phenolate moiety was modified to contain
      electron-donating or -withdrawing groups (-CH(3), -H, -Br, -NO(2)) in the 5
      position. The effects of the substituents on the electronic properties of the
      biomimetic complexes were studied with a range of experimental and computational
      techniques. This study establishes benchmarks against accurate crystallographic
      structural information using spectroscopic techniques that are not restricted to
      single crystals. Kinetic studies on the hydrolysis reaction revealed that the
      phosphodiesterase activity increases in the order -NO(2) <-Br <-H <-CH(3) when
      2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear
      free energy relationship is found when log(k(cat)/k(0)) is plotted against the
      Hammett parameter sigma. However, nuclease activity measurements in the cleavage
      of double stranded DNA showed that the complexes containing the electron
      withdrawing -NO(2) and electron-donating -CH(3) groups are the most active while
      the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is
      highest for complexes with electron-donating groups.

PMID- 21080711
TI  - Volatile compounds and sensory attributes of wine from Cv. Merlot (Vitis vinifera
      L.) grown under differential levels of water deficit with or without a kaolin
      based, foliar reflectant particle film.
AB  - The volatile composition and sensory attributes of Merlot wines produced from
      vines under differing levels of water stress, with or without a foliar, kaolin
      based particle film, were analyzed by stir bar sorptive extraction-gas
      chromatography-mass spectrometry (SBSE-GC-MS) and sensory evaluation. Vines were
      irrigated over consecutive vintages with 100, 70, or 35% of their estimated water
      requirements (ET(c)), or 35% until color change then 70% until harvest (35-70%
      ET(c)). Neither of the treatments consistently influenced ester concentrations or
      their relative amounts, though their concentrations varied from year to year.
      However, deficit irrigation had an effect on the concentration of terpene
      alcohols and norisoprenoids. Wines produced from vines under water deficit
      contained higher amounts of citronellol, nerol, geraniol, and beta-damascenone,
      but linalool and beta-ionone were not affected by deficit irrigation. Particle
      film did not affect volatile composition in the wine. Untrained panelists in 2007
      and 2008 distinguished between wines from vines that received 100 or 35% ET(c)
      and between wines from vines that received 35 or 35-70% ET(c). Trained sensory
      panelists detected differences among wines for aroma, flavor, taste, and
      mouthfeel; however, significant interactive effects between particle film
      application and vine water status hindered interpretation of independent main
      effects.

PMID- 21080712
TI  - Lycopene degradation and isomerization kinetics during thermal processing of an
      olive oil/tomato emulsion.
AB  - The stability of lycopene in an olive oil/tomato emulsion during thermal
      processing (80-140  degrees C) was studied. Initially, the degradation of total
      lycopene (all-E plus Z-forms) occurred quickly at temperatures above 100  degrees
      C. However, a nonzero plateau value, depending on the processing temperature, was
      attained after longer treatment times. Besides degradation, the isomerization of
      total-Z-lycopene as well as the individual isomerization of all-E-, 5-Z-, 9-Z-,
      and 13-Z-lycopene was studied in detail. After prolonged heating, the isomer
      conversion reached a temperature-dependent equilibrium state. The degradation of
      total lycopene and the isomerization could be described by a fractional
      conversion model. The temperature dependency of the corresponding reaction rate
      constants was quantified by the Arrhenius equation. The activation energy of
      degradation was estimated to be 28 kJ/mol, and the activation energy of overall
      (all-E and total-Z) isomerization was estimated to be 52 kJ/mol.

PMID- 21080713
TI  - Mass spectral analyses of corn stover prehydrolysates to assess conditioning
      processes.
AB  - Flow injection electrospray (FIE) and LC-tandem mass spectrometry techniques were
      used to characterize corn stover acid hydrolysates before and after overliming
      and ammonia conditioning steps. Analyses were performed on samples without
      fractionation (dilution only) in an effort provide an inventory of ionizable
      substances. Statistical evaluation of the results indicates that the ammonia
      treated and crude hydrolysates were more similar to one another than any other
      pairing, with conditioning leading to a decrease in malate levels. LC-tandem mass
      spectrometry studies were also developed to characterize the oligosaccharides
      present in each hydrolysate utilizing a hydrophilic interaction chromatographic
      separation method. Neutral and acidic pentose-based oligosaccharides
      (xylodextrins) with degrees of polymerization between 2 and 5 were quantified
      with 4-O-methyl glucuronic acid-containing dimer and trimers predominating.
      Conditioning had little effect on the quantified oligosaccharide pool.

PMID- 21080714
TI  - The effect of Monascus secondary polyketide metabolites, monascin and ankaflavin,
      on adipogenesis and lipolysis activity in 3T3-L1.
AB  - The aim of the present work is to investigate the effects of Monascus secondary
      metabolites, monascin (MS) and ankaflavin (AK), on cell proliferation,
      adipogenesis, lipolysis and heparin-releasable lipoprotein lipase (HR-LPL) in 3T3
      L1 preadipocyte. MS and AK inhibit the proliferation of 3T3-L1 cells in a dose
      dependent fashion. At 8 MUg/mL concentration MS inhibits proliferation for 80.5%
      after 48 h, whereas the value for AK is 69.2%. Adipogenesis is inhibited by MS
      and AK without dose-dependency. Triglyceride is decreased 37.1% and 41.1%
      respectively by treating 0.125 MUg/mL MS and AK. Adipocyte-specific transcription
      factors peroxisome proliferator-activated receptor gamma (PPARgamma),
      CCAAT/enhancer binding protein beta (C/EBPbeta), C/EBPdelta and C/EBPalpha mRNA
      levels are measured by real-time polymerase chain reaction. The expression of the
      four transcriptional factors analyzed (PPARgamma, C/EBPbeta, C/EBPdelta and
      C/EBPalpha) is reduced at the initial and the middle period. At the later period,
      there is no effect on the expression of PPARgamma and C/EBPalpha by treating MS
      and AK. Furthermore, both MS and AK increase basal lipolysis of mature adipocytes
      by 113.2% and 278.3% upregulation, respectively. And both MS and AK reduce the
      activity of HR-LPL, by 45.3% and 58.1% reduction, respectively. This study
      reveals for the first time that Monascus secondary metabolites, MS and AK, can
      prevent the differentiation of preadipocyte and stimulate basal lipolysis of
      mature adipocytes, avoiding the accumulation of lipid.

PMID- 21080715
TI  - Anion exchange kinetics of nanodimensional layered metal hydroxides: use of
      isoconversional analysis.
AB  - Anion exchange reactions of nanodimensional layered metal hydroxide compounds are
      utilized to create materials with targeted physical and chemical properties and
      also as a means for controlled release of intercalated anions. The kinetics of
      this important class of reaction are generally characterized by model-based
      approaches. In this work, a different approach based on isothermal,
      isoconversional analysis was utilized to determine effective activation energies
      with respect to extent of reaction. Two different layered metal hydroxide
      materials were chosen for reaction with chloride anions, using a temperature
      range of 30-60  degrees C. The concentrations of anions released into solution
      and the changes in polycrystalline solid phases were evaluated using model-based
      (Avrami-Erofe'ev nucleation-growth model) and model-free (integral
      isoconversional) methods. The results demonstrate the utility of the
      isoconversional approach for identifying when fitting to a single model is not
      appropriate, particularly for characterizing the temperature dependence of the
      reaction kinetics.

PMID- 21080716
TI  - Do traditional, chlorine-shared, and ion-pair halogen bonds exist? An ab initio
      investigation of FCl:CNX complexes.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to determine the
      structures, binding energies, and bonding of complexes FCl:CNX, with X = CN, NC,
      NO(2), F, CF(3), Cl, Br, H, CCF, CCH, CH(3), SiH(3), Li, and Na. Equation-of
      motion coupled cluster calculations have also been carried out to determine the
      coupling constants (1)J(F-Cl), (1X)J(Cl-C), and (2X)J(F-C) across these halogen
      bonds. As the strength of the base is systematically increased, the nature of the
      halogen bond changes from traditional, to chlorine-shared, to ion-pair. The type
      of halogen bond present in a complex can be readily determined from its
      structure, binding energy, AIM bonding analyses, and spin-spin coupling
      constants. Coupling constants across halogen bonds are compared with
      corresponding coupling constants across traditional, proton-shared, and ion-pair
      hydrogen bonds.

PMID- 21080717
TI  - High-accuracy theoretical study on the thermochemistry of several formaldehyde
      derivatives.
AB  - In the case of several formaldehyde derivatives, with importance in atmospheric
      and combustion chemistry, the currently available thermochemical values suffer
      from considerably large uncertainties. In this study a high-accuracy theoretical
      model chemistry has been used to provide accurate thermochemical data including
      heats of formation at 0 and 298 K and standard molar entropies at 298 K for
      CF(2)O, FCO, HFCO, HClCO, FClCO, HOCO, and NH(2)CO. For most of the
      thermochemical quantities studied here, this investigation delivers the best
      available estimate.

PMID- 21080718
TI  - Environmental broadening of the CTTS bands: the hexaammineruthenium(II) complex
      in aqueous solution.
AB  - Cluster ab initio quantum chemistry approach is developed to simulate the charge
      transfer-to-solvent (CTTS) absorption band and satellite ligand field bands of
      hexaammineruthenium(II) ion in aqueous solution. Several cluster models,
      including 16, 21, and 38 water molecules, are explored for this purpose. TDDFT
      method with long-range corrected BLYP (LC-BLYP) functional is used to obtain the
      vertical transition characteristics, and DFT B3LYP is used for calculation of the
      ground state geometry and vibrational frequencies of the solvated complex. A
      simple harmonic bath model is employed to estimate the absorption bandwidths and
      coherence decay times with the parameters taken from the quantum chemistry
      calculations. The present approach provides rather reasonable estimates for the
      CTTS band position and shape, also giving an additional insight for the mechanism
      of the CTTS band broadening.

PMID- 21080719
TI  - Theoretical study of the mechanism of valence tautomerism in cobalt complexes.
AB  - Valence tautomerism is studied in the [Co(II-HS)(sq)(2)(bpy)]/[Co(III
      LS)(sq)(cat)(bpy)] mononuclear cobalt complex by using DFT methods (HS, high
      spin; LS, low spin; cat, catecholate; sq, semiquinone; bpy, 2,2'-bipyridine).
      Calculations at the B3LYP* level of theory reproduce well the energy gap between
      the Co(II-HS) and Co(III-LS) forms giving an energy gap of 4.4 kcal/mol, which is
      comparable to the experimental value of 8.9 kcal/mol. Potential energy surfaces
      and crossing seams of the electronic states of the doublet, quartet, and sextet
      spin states are calculated along minimum energy paths connecting the energy
      minima corresponding to the different spin states. The calculated minimum energy
      crossing points (MECPs) are located at 8.8 kcal/mol in the doublet/sextet
      surfaces, at 10.2 kcal/mol in the doublet/quartet surfaces, and at 8.4 kcal/mol
      in the quartet/sextet surfaces relative to the doublet ground state. Considering
      the energy of the three spin states and the crossing points, the one-step
      relaxation mechanism between the Co(II-HS) and Co(III-LS) forms is the most
      probable. This research shows that mapping MECPs can be a useful strategy to
      analyze the potential energy surfaces of systems with complex deformation modes.

PMID- 21080720
TI  - Quartz crystal microbalances for microscale thermogravimetric analysis.
AB  - A new method for analyzing the chemical purity and consistency of microscale
      samples with a quartz crystal microbalance (QCM) sensor platform is described.
      The QCM is used to monitor submicrogram changes in the mass of a deposited thin
      film as a function of temperature, in a manner similar to that of a conventional
      thermogravimetric analyzer (TGA). Results correlated well with TGA measurements
      for a wide range of representative materials, including organic compounds, ionic
      detergents, oxidizing and inert powders, carbon nanotubes, and various mixtures
      of these samples. In each case, the sample mass was on the order of a few
      micrograms, compared to the need for several milligrams for conventional TGA
      analysis. This work illustrates the effectiveness of this approach for analysis
      of nanoparticles, thin films, and highly purified specimens on the microgram
      scale.

PMID- 21080721
TI  - Nucleophilicity and accessibility calculations of alkanolamines: applications to
      carbon dioxide absorption reactions.
AB  - Both nucleophilicities and accessibilities of three alkanolamines
      [monoethanolamine (MEA), (2-(methylamino)ethanol (MAE), and 2-amino-2-methyl-1
      propanol (AMP)] were calculated to predict their reactivities with CO(2). After
      DFT geometry-optimization calculations, the global, group, and atomic
      nucleophilicities of each amine were obtained using MP2 quantum mechanical
      calculations. Only global nucleophilicity matched an experimental pK(a) order
      (MAE > AMP > MEA). However, it failed to predict the slow rate of the sterically
      hindered AMP and the order of rate constants, MAE > MEA > AMP. The
      accessibilities of amines to CO(2) have been calculated by MD simulations by
      monitoring collisions at the reaction centers: N atoms in amines and C in CO(2).
      The accessibility results indicate that global nucleophilicity needs quantitative
      correction for steric effects to predict better reactivities of amines with
      CO(2).

PMID- 21080723
TI  - Synthesis of amino-1,2,4-triazoles by reductive ANRORC rearrangements of 1,2,4
      oxadiazoles.
AB  - The reaction of various 1,2,4-oxadiazoles with an excess of hydrazine in DMF has
      been investigated. 3-Amino-1,2,4-triazoles are produced through a reductive
      ANRORC pathway consisting of the addition of hydrazine to the 1,2,4-oxadiazole
      followed by ring-opening, ring-closure, and final reduction of the 3
      hydroxylamino-1,2,4-triazole intermediate. The general applicability of 1,2,4
      oxadiazoles ANRORC reactivity is demonstrated also in the absence of C(5)-linked
      electron-withdrawing groups.

PMID- 21080722
TI  - DNA-dependent protein kinase (DNA-PK) inhibitors. Synthesis and biological
      activity of quinolin-4-one and pyridopyrimidin-4-one surrogates for the chromen-4
      one chemotype.
AB  - Following the discovery of dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4
      one (NU7441) ( Leahy , J. J. J. ; Golding , B. T. ; Griffin , R. J. ; Hardcastle
      , I. R. ; Richardson , C. ; Rigoreau , L. ; Smith , G. C. M. Bioorg. Med. Chem.
      Lett. 2004 , 14 , 6083 - 6087) as a potent inhibitor (IC50 = 30 nM) of DNA
      dependent protein kinase (DNA-PK), we have investigated analogues in which the
      chromen-4-one core template has been replaced by aza-heterocyclic systems: 9
      substituted 2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-ones and 8-substituted 2
      morpholin-4-yl-1H-quinolin-4-ones. The 8- and 9-substituents were either
      dibenzothiophen-4-yl or dibenzofuran-4-yl, which were each further substituted at
      the 1-position with water-solubilizing groups [NHCO(CH2)(n)NR1R2, where n = 1 or
      2 and the moiety R1R2N was derived from a library of primary and secondary amines
      (e.g., morpholine)]. The inhibitors were synthesized by employing a multiple
      parallel approach in which the two heterocyclic components were assembled by
      Suzuki-Miyaura cross-coupling. Potent DNA-PK inhibitory activity was generally
      observed across the compound series, with structure-activity studies indicating
      that optimal potency resided in pyridopyrimidin-4-ones bearing a substituted
      dibenzothiophen-4-yl group. Several of the newly synthesized compounds (e.g., 2
      morpholin-4-yl-N-[4-(2-morpholin-4-yl-4-oxo-4H-pyrido[1,2-a]pyrimidin-9
      yl)dibenzothiophen-1-yl]acetamide) combined high potency against the target
      enzyme (DNA-PK IC50 = 8 nM) with promising activity as potentiators of ionizing
      radiation-induced cytotoxicity in vitro.

PMID- 21080724
TI  - Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methylprop-2
      ynylamino]-N-(3-pyridylmethyl)benzamide (CB-30865) as potent inhibitors of
      nicotinamide phosphoribosyltransferase (Nampt).
AB  - We have shown previously that the target of the potent cytotoxic agent 4-[(7
      bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3
      pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase
      (Nampt). With its cellular target known we sought to optimize the biochemical and
      cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3
      pyridylmethylamide substituent in the A region was critical to cellular Nampt
      activity and cytotoxicity, although other aromatic substitution did yield
      compounds with submicromolar enzymatic inhibition. Small unsaturated groups
      worked best in the D-region of the molecule, with 3,3-dimethylallyl providing
      optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4
      one group for activity, and many substituents were tolerated at C2 of the
      quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and
      low nanomolar cytotoxicity in cellular assays.

PMID- 21080725
TI  - Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as
      tubulin targeting agents.
AB  - The synthesis and antiproliferative activity of a new series of rigid analogues
      of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone
      (beta-lactam) ring system in place of the usual ethylene bridge present in the
      natural combretastatin stilbene products. These novel compounds are also
      substituted at position 3 of the beta-lactam ring with an aryl ring. A number of
      analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast
      cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and
      did not cause significant cytotoxicity in normal murine breast epithelial cells.
      4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)
      substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46
      and 47 displayed the most potent antiproliferative activity of the series. beta
      Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells
      (IC50= 0.8 nM) together with significant in vitro inhibition of tubulin
      polymerization and has been selected for further biochemical assessment. These
      novel beta-lactam compounds are identified as potentially useful scaffolds for
      the further development of antitumor agents that target tubulin.

PMID- 21080727
TI  - Quantitative proteomic analysis of tumor reversion in multiple myeloma cells.
AB  - Tumor reversion is defined as the process by which cancer cells lose their
      malignant phenotype. However, relatively little is known about the cellular
      proteome changes that occur during the reversion process. A biological model of
      multiple myeloma (MM) reversion was established by using the H-1 parvovirus as a
      tool to select for revertant cells from MM cells. Isolated revertant cells
      displayed a strongly suppressed malignant phenotype both in vitro and in vivo. To
      explore possible mechanisms of MM reversion, the protein profiles of the
      revertant and parental MM cells were compared using a quantitative proteomic
      strategy termed SILAC-MS. Our results revealed that 379 proteins were either
      activated or inhibited during the reversion process, with a much greater
      proportion of the proteins, including STAT3, TCTP, CDC2, BAG2, and PCNA, being
      inhibited. Of these, STAT3, which is significantly down regulated, was selected
      for further functional studies. Inhibition of STAT3 expression by RNA
      interference resulted in suppression of the malignant phenotype and concomitant
      down regulation of TCTP expression, suggesting that myeloma reversion operates,
      at least in part, through inhibition of STAT3. Our results provide novel insights
      into the mechanisms of tumor reversion and suggest new alternative approaches for
      MM treatment.

PMID- 21080726
TI  - Influence of histatin 5 on Candida albicans mitochondrial protein expression
      assessed by quantitative mass spectrometry.
AB  - Individual aspects of the mode of action of histatin 5, a human salivary
      antifungal protein, have been partially elucidated, but the mechanism likely
      involves a complex set of events that have not been characterized. Previous
      evidence points toward histatin-induced alterations in mitochondrial function.
      The purpose of the present study was to verify and quantify changes in the
      mitochondrial proteome of Candida albicans treated with histatin 5. Cell killing
      was determined by plating and differential protein expression levels in the
      mitochondrial samples were determined by quantitative proteomics approaches
      employing mTRAQ and ICAT labeling and Western blotting. Relative quantitation
      ratios were established for 144 different proteins. Up-regulated mitochondrial
      proteins were predominantly involved in genome maintenance and gene expression,
      whereas proteins that constitute the respiratory enzyme complexes were mostly
      down-regulated. The differential expression of ATP synthase gamma chain and
      elongation factor 1-alpha were confirmed by Western blotting by comparison to
      levels of cytochrome c which were unchanged upon histatin treatment. The mTRAQ
      and ICAT proteomics results suggest that key steps in the histatin 5 antifungal
      mechanism involve a bioenergetic collapse of C. albicans, caused essentially by a
      decrease in mitochondrial ATP synthesis.

PMID- 21080728
TI  - Study of the polyphenolic composition and antioxidant activity of new sherry
      vinegar-derived products by maceration with fruits.
AB  - Several experiments of maceration of a sherry wine vinegar with different fruits
      (orange, lemon, strawberry, grapefruit, and lime) have been carried out. After
      optimization (only peel, no heating and seven days as maximum time of
      maceration), parameters such as polyphenolic content, superoxide anion scavenging
      ability (related to antioxidant activity) and ascorbic acid content were
      determined in sherry wine vinegars macerated with two amounts of peel and for two
      maceration times (3 and 7 days). The analysis of variance pointed to a clear
      relationship (p<0.01) between type of fruit and amount of peel and polyphenolic
      content. The factor "time" was practically not significant for any polyphenol.
      Sherry wine vinegars macerated with different fruits exhibited higher superoxide
      anion scavenger ability, with the maximum values found for the vinegar macerated
      with lemon peel. The correlation analysis showed that the superoxide anion
      scavenger ability of the vinegars macerated, and thus their antioxidant activity,
      was highly correlated (p<0.01) with several polyphenols, especially with
      naringin, hesperidin, neohesperidin and gentisic acid and not with the ascorbic
      acid content.

PMID- 21080729
TI  - Systems responses of rats to aflatoxin B1 exposure revealed with metabonomic
      changes in multiple biological matrices.
AB  - Exposure to aflatoxins causes liver fibrosis and hepatocellular carcinoma posing
      a significant health risk for human populations and livestock. To understand the
      mammalian systems responses to aflatoxin-B1 (AFB1) exposure, we analyzed the AFB1
      induced metabonomic changes in multiple biological matrices (plasma, urine, and
      liver) of rats using (1)H NMR spectroscopy together with clinical biochemistry
      and histopathologic assessments. We found that AFB1 exposure caused significant
      elevation of glucose, amino acids, and choline metabolites (choline,
      phosphocholine, and glycerophosphocholine) in plasma but reduction of plasma
      lipids. AFB1 also induced elevation of liver lipids, amino acids (tyrosine,
      histidine, phenylalanine, leucine, isoleucine, and valine), choline, and nucleic
      acid metabolites (inosine, adenosine, and uridine) together with reduction of
      hepatic glycogen and glucose. AFB1 further caused decreases in urinary TCA cycle
      intermediates (2-oxoglutarate and citrate) and elevation of gut microbiota
      cometabolites (phenylacetylglycine and hippurate). These indicated that AFB1
      exposure caused hepatic steatosis accompanied with widespread metabolic changes
      including lipid and cell membrane metabolisms, protein biosynthesis, glycolysis,
      TCA cycle, and gut microbiota functions. This implied that AFB1 exposure probably
      caused oxidative-stress-mediated impairments of mitochondria functions. These
      findings provide an overview of biochemical consequences of AFB1 exposure and
      comprehensive insights into the metabolic aspects of AFB1-induced hepatotoxicity
      in rats.

PMID- 21080730
TI  - Nationwide Health Data Management System: a novel approach for integrating
      biomarker measurements with comprehensive health records in large populations
      studies.
AB  - The nation-wide electronic health record database acts as an interoperable
      repository of health data obtained throughout citizen contacts with health care
      providers. This system improves accessibility for citizens and researchers to
      health data with the ability to assign context to disease development. In that
      system, individual patients who are members of the large population-based health
      database can be assessed as individuals or as a population in prospective studies
      of prospective diseases.

PMID- 21080732
TI  - Is there a role for pharmacoeconomics in developing countries?

PMID- 21080733
TI  - The economics of a 'liberated' NHS.

PMID- 21080734
TI  - The analysis of multinational cost-effectiveness data for reimbursement
      decisions: a critical appraisal of recent methodological developments.
AB  - Evidence produced by multinational trial-based cost-effectiveness studies is
      often used to inform decisions concerning the adoption of new healthcare
      technologies. A key issue relating to the use of this type of evidence is the
      extent to which trial-wide economic results are applicable to every single
      country participating in the study. We consider what role cost-effectiveness
      analysis alongside multinational trials should have in assisting reimbursement
      decisions at jurisdiction and national levels. Using the proposed framework as a
      benchmark to evaluate their relative pros and cons, we then describe and review
      the statistical approaches used in the multinational trial-based cost
      effectiveness literature. The results of the review are used to define the
      desirable characteristics a statistical method for the analysis of data collected
      from different jurisdictions should have in order to be consistent with the
      proposed framework. It is argued that Bayesian hierarchical models that use both
      patient- and country-level information are the most appropriate tool to analyse
      multinational trial-based cost-effectiveness data and facilitate the between
      country generalizability assessment of the study findings. The merits of each
      approach are discussed, highlighting problems and limitations, in order to
      identify areas of future research.

PMID- 21080735
TI  - Concordance of adherence measurement using self-reported adherence questionnaires
      and medication monitoring devices.
AB  - The primary objective of this review was to identify and examine the literature
      on the association between medication adherence self-reported questionnaires
      (SRQs) and medication monitoring devices. The primary literature search was
      performed for 1980-2009 using PubMed, PubMed In Process and Non-Indexed, Ovid
      MEDLINE, Ovid MEDLINE In-Process, PsycINFO (EBSCO), CINAHL (EBSCO), Ovid
      HealthStar, EMBASE (Elsevier) and Cochrane Databases and using the following
      search terms: 'patient compliance', 'medication adherence', 'treatment
      compliance', 'drug monitoring', 'drug therapy', 'electronic', 'digital',
      'computer', 'monitor', 'monitoring', 'drug', 'drugs', 'pharmaceutical
      preparations', 'compliance' and 'medications'. We identified studies that
      included SRQs and electronic monitoring devices to measure adherence and focused
      on the SRQs that were found to be moderately to highly correlated with the
      monitoring devices. Of the 1679 citations found via the primary search, 41 full
      text articles were reviewed for correlation between monitoring devices and SRQs.
      A majority (68%) of articles reported high (27%), moderate (29%) or significant
      (12%) correlation between monitoring devices (37 using Medication Event
      Monitoring System [MEMS(r)] and four using other devices) and SRQs (11 identified
      and numerous other unnamed SRQs). The most commonly used SRQs were the
      Adult/Pediatric AIDS Clinical Trial Group (AACTG/PACTG; 24.4%, 10/41) followed by
      the 4-item Morisky (9.8%, 4/41), Brief Medication Questionnaire (9.8%, 4/41) and
      visual analogue scale (VAS; 7.3%, 3/41). Although study designs differed across
      the articles, SRQs appeared to report a higher rate of medication adherence
      (+14.9%) than monitoring devices. In conclusion, several medication adherence
      SRQs were validated using electronic monitoring devices. A majority of them
      showed high or moderate correlation with medication adherence measured using
      monitoring devices, and could be considered for measuring patient-reported
      adherence prospectively.

PMID- 21080736
TI  - A review and critique of studies reporting utility values for schizophrenia
      related health states.
AB  - Economic evaluation of health technologies in the form of cost-utility analysis
      is increasingly advocated. The most common outcome measure in this type of
      analysis is the QALY. In order to estimate QALYs, appropriate utility values are
      required. The objective of this review was to identify and critique utility
      values for schizophrenia-related health states. A critical appraisal was
      performed on utility values for schizophrenia identified in the systematic
      literature review that informed the economic analysis of the updated edition of
      the National Institute for Health and Clinical Excellence (NICE) clinical
      guideline on schizophrenia for England and Wales. Seven studies reporting utility
      values for schizophrenia were identified. The studies employed a variety of
      methods for generating utility values. None of the reported sets of utility
      values for schizophrenia were generated using the EQ-5D, which is a measure
      widely used in cost-utility analysis and preferred by NICE. Nevertheless, the EQ
      5D may be less sensitive in capturing aspects of health-related quality of life
      in patients with schizophrenia. A condition-specific preference-based instrument
      may be more appropriate than a generic measure to inform cost-utility analyses of
      interventions for schizophrenia.

PMID- 21080737
TI  - The cost utility of autologous chondrocytes implantation using ChondroCelect(r)
      in symptomatic knee cartilage lesions in Belgium.
AB  - BACKGROUND: Knee cartilage lesions increase the risk of developing osteoarthritis
      (OA), and may eventually result in a total knee replacement (TKR). There is
      currently no consensus on the optimal treatment of cartilage lesions.
      ChondroCelect(r) (CC) is a cell-based therapy approved for use in autologous
      chondrocytes implantation (ACI) to treat symptomatic cartilage defects of the
      femoral condyle. Its capacity to safely restore good-quality cartilage was
      demonstrated in a randomized controlled trial (RCT) versus the surgical procedure
      microfracture (MFX). OBJECTIVE: This study investigated the cost utility of CC
      used in ACI compared with MFX to treat symptomatic knee cartilage lesions in
      Belgium. METHODS: A decision tree model comparing CC with MFX over a 40-year
      horizon was developed in TreeAge ProTM. The key timepoints of the model were (i)
      clinical assessment 5 years after initial intervention (success or no success,
      with or without re-operation); (ii) development of OA at 15 years (yes/no); (iii)
      need for TKR at 20 years (yes/no); and (iv) need for prosthesis revision at 35
      years (yes/no). Clinical data provided by the RCT of CC versus MFX were the
      clinical success (response) rate based on the Knee injury and Osteoarthritis
      Outcome Score (KOOS) at 36 months (82.9% vs 62.0%; p = 0.048) and the proportion
      of good structural repair/presence of hyaline cartilage based on International
      Cartilage Repair Society (ICRS II) visual item at 12 months (44.9% vs 23.2%; p =
      0.023). Utility scores by surgery outcome were derived from the SF-36
      questionnaire responses collected in the RCT. Conservative assumptions related to
      the incidences of OA, TKR and prosthesis revision relied on a literature search.
      A patient chart review (n = 82) provided follow-up costs by surgery outcome.
      National tariffs were applied to direct medical resources used (healthcare payer
      perspective, year 2008 costs). Annual discounting was applied to costs (3%) and
      effects (1.5%) as recommended by the Belgian pharmacoeconomic guidelines.
      RESULTS: The incremental cost per QALY gained for CC compared with MFX was
      ?16,229, with a difference in costs of ?20,802 and 1.282 QALYs gained.
      Sensitivity analyses indicated that the key model drivers were the proportion of
      patients with hyaline cartilage and the correlation between hyaline cartilage
      formation and later avoidance of OA. Probabilistic sensitivity analyses showed
      robustness of the results, with 80% of the simulations below the usual UK
      National Institute for Health and Clinical Excellence (NICE) threshold of ?22,000
      per QALY. CONCLUSIONS: Assuming a good correlation between high-quality cartilage
      repair and avoidance of OA at a later stage, the benefits of the cell therapy CC
      over MFX in terms of QALYs gained and OA-related costs avoided appear real.
      Further research is required to explore long-term effects of cartilage repair and
      reduce uncertainty on quality of life of patients with OA before and after joint
      replacement.

PMID- 21080738
TI  - Drugs in development for tuberculosis.
AB  - Tuberculosis (TB) drug research and development efforts have resurged in the past
      10 years to meet urgent medical needs, but enormous challenges remain. These
      urgent needs are largely driven by the current long and arduous multidrug
      regimens, which have significant safety, tolerability and compliance issues;
      rising and disturbing rates of multidrug- and extensively drug-resistant TB; the
      existence of approximately 2 billion individuals already latently infected with
      Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co
      epidemic. Stakeholders in TB drug development are moving to enable and streamline
      development and registration of novel, multidrug treatment regimens, comprised of
      multiple new chemical entities with novel mechanisms of action that do not
      demonstrate cross-resistance to current first- and second-line TB drugs. Ideally,
      these new regimens will ultimately provide a short, simple treatment suitable for
      essentially all TB patients, whether sensitive or resistant to the current anti
      TB agents, whether HIV-positive or -negative, and irrespective of patient age.
      This article reviews the challenges faced by those trying to develop these novel
      regimens and the key agents currently in clinical testing for TB; the latter are
      organized for discussion into three categories: (i) novel drugs (TMC207, SQ109,
      sudoterb [LL3858]); (ii) present first-line TB drugs being re-evaluated to
      optimize their efficacy (rifampicin, rifapentine); and (iii) currently licensed
      drugs for other indications and 'next-generation' compounds of the same chemical
      class being repurposed for TB (gatifloxacin and moxifloxacin; linezolid,
      PNU100480 and AZD5847; metronidazole, OPC-67683 and PA-824).

PMID- 21080740
TI  - Influence of intensive versus conventional glucose control on microvascular and
      macrovascular complications in type 1 and 2 diabetes mellitus.
AB  - In type 1 and 2 diabetes mellitus patients, hyperglycaemia is independently
      related to the development of microvascular and macrovascular complications.
      Glycaemic targets and the benefits of intensive versus conventional glucose
      control are under debate. The purpose of this review is to provide an overview of
      the randomized controlled trials and meta-analyses comparing the effects of
      intensive versus conventional glucose control on microvascular and macrovascular
      complications in type 1 and 2 diabetes. MEDLINE and Cochrane database searches
      were performed with a limit on randomized controlled trials or meta-analysis and
      keywords related to glucose control and diabetes. In addition, related articles
      and reference lists of relevant articles and guidelines were reviewed. Nine
      randomized controlled trials, three in type 1 and six in type 2 diabetes, and
      four meta-analyses in type 2 diabetes were reviewed. These studies included more
      than 30,000 patients. On the basis of these trials and meta-analyses, it can be
      concluded that intensive glucose control has a beneficial effect on microvascular
      complications (retinopathy, nephropathy, neuropathy) in both type 1 and type 2
      diabetes patients. The risk reduction of developing a microvascular complication
      varied between 25% and 76%. Particularly in patients with type 2 diabetes, there
      was a 10-15% decrease in nonfatal myocardial infarction with intensive glucose
      control, but no effect on stroke, cardiovascular death or all-cause mortality was
      observed. There was a beneficial effect of intensive glucose control on
      cardiovascular disease in patients with type 1 diabetes in only one trial. In all
      studies, intensive glucose control was associated with at least twice the risk
      for serious hypoglycaemia than the conventional-control group. In conclusion,
      compared with conventional glucose control, intensive glucose control is
      associated with fewer microvascular complications in both type 1 and type 2
      diabetes, a decrease in coronary events, especially in type 2 diabetes, and more
      serious hypoglycaemia.

PMID- 21080739
TI  - Pharmacological management of essential tremor.
AB  - Essential tremor (ET) is a common movement disorder with clinical features that
      manifest with both motor (tremor and balance disorders) and non-motor (such as
      mild cognitive deficits and hearing loss) symptoms. The diagnosis of ET is based
      on the presence of an action tremor of greater severity than enhanced
      physiological tremor, without other identifiable causes. Patients with ET
      experience a decrease in the performance of their motor skills and social
      activities, and a decline in their quality of life. The pathophysiology of ET is
      still not clear. Pharmacotherapy for ET is indicated if the disease interferes
      with the patient's quality of life. Propranolol, a nonselective beta-adrenergic
      receptor antagonist, and primidone, an antiepileptic, remain the standard
      treatments for ET. However, studies show that several other agents, including
      topiramate, gabapentin and zonisamide, might also be beneficial. Local injections
      of botulinum toxins and surgical interventions such as thalamic deep brain
      stimulation play a role as alternative options when pharmacological treatment is
      not satisfactory. Several new agents including 1-octanol, pregabalin and sodium
      oxybate are currently under investigation.

PMID- 21080741
TI  - Triple-negative breast cancer: epidemiology and management options.
AB  - The triple receptor-negative breast cancer (TNBC) subtype is characterized by the
      lack of expression of both hormone receptors as well as lack of over-expression
      and/or lack of gene amplification of human epidermal growth factor receptor 2
      (HER2). Approximately 10-15% of breast carcinomas are known to be of the TNBC
      subtype, which constitutes approximately 80% of all 'basal-like tumours'. Risk
      factors for TNBC include young age at breast cancer diagnosis, young age at
      menarche, high parity, lack of breast feeding, high body mass index and African
      American ethnicity. The majority of BRCA1 tumours are TNBC. TNBC has a worse
      prognosis and tends to relapse early compared with other subtypes of breast
      cancer. Conversely, it displays increased chemosensitivity compared with other
      breast tumour subtypes. Several agents are currently being investigated as
      potential therapeutic agents for the treatment of women with TNBC including
      agents targeted against EGFR, anti-angiogenic agents, multityrosine kinase
      inhibitors and poly (ADP-ribose) polymerase (PARP) inhibitors. This review
      focuses on the epidemiology of TNBC, its pathological features, natural history
      and recurrence patterns as well as current and future management options.

PMID- 21080742
TI  - Trastuzumab: in HER2-positive metastatic gastric cancer.
AB  - Trastuzumab is a recombinant humanized IgG1 monoclonal antibody directed against
      the extracellular domain of the human epidermal growth factor receptor type 2
      (HER2) that inhibits HER2-dependent tumour cell proliferation and survival.
      Proliferation of gastric cancer cells overexpressing HER2 is inhibited by
      trastuzumab in vitro and in vivo. HER2-positive expression (defined as
      immunohistochemistry 3+ or fluorescence in situ hybridization-positive) was
      observed in 22.1% of almost 4000 metastatic gastric cancers in patients who were
      screened for randomization in the open-label, multicentre, phase III ToGA trial.
      In patients with HER2-positive metastatic gastric cancer (n = 584), median
      overall survival (primary endpoint) was significantly longer for recipients of
      intravenous trastuzumab plus chemotherapy (comprising cisplatin and either
      fluorouracil or capecitabine) than in those receiving chemotherapy alone in the
      ToGA trial. Furthermore, the overall response rate was significantly higher and
      the median time to disease progression and median time of progression-free
      survival were also significantly longer with trastuzumab plus chemotherapy than
      with chemotherapy alone. In general, combination therapy with trastuzumab and
      chemotherapy was relatively well tolerated in patients with metastatic gastric
      cancer with no reports of new or unexpected adverse events.

PMID- 21080743
TI  - Indacaterol: in chronic obstructive pulmonary disease.
AB  - Indacaterol is a long-acting beta2-adrenoceptor agonist that is available in the
      EU for the maintenance treatment of airflow obstruction in adult patients with
      chronic obstructive pulmonary disease (COPD). Indacaterol has a 24-hour
      bronchodilatory effect, which allows for once-daily administration. The onset of
      bronchodilation after inhalation of indacaterol is fast, with significant
      improvements versus placebo seen 5 minutes after inhalation. In four large (n >
      400), randomized, double-blind, placebo-controlled, multicentre phase III trials,
      patients with COPD who received indacaterol 150 or 300 MUg once daily had a
      significantly higher mean trough forced expiratory volume in 1 second (FEV1) than
      placebo recipients after 12 weeks. Trough FEV1 differences between indacaterol
      and placebo recipients were 130-180 mL and exceeded the clinically relevant
      threshold of 120 mL in all trials. Furthermore, indacaterol recipients had
      significantly higher mean trough FEV1 values after 12 weeks than patients who
      received formoterol, salmeterol or open-label tiotropium. COPD exacerbations and
      symptoms, and health-related quality of life were also significantly improved for
      indacaterol versus placebo recipients in some studies. Indacaterol was generally
      well tolerated by adults with moderate to severe COPD.

PMID- 21080744
TI  - Fentanyl sublingual: in breakthrough pain in opioid-tolerant adults with cancer.
AB  - Fentanyl is a potent opioid with a short duration of action. Fentanyl sublingual
      has been formulated as a rapidly disintegrating tablet that is quickly absorbed,
      producing a fast onset of analgesia. In two randomized, double-blind clinical
      trials, fentanyl sublingual as single fixed or titrated doses reduced pain
      intensity during breakthrough pain episodes to a significantly greater extent
      than placebo in opioid-tolerant cancer patients. In a fixed-dose phase II trial
      and a titrated-dose phase III trial, fentanyl sublingual (as a single 400 MUg
      dose and as titrated doses) reduced mean pain intensity difference (PID) to a
      significantly greater extent than placebo over the entire treatment period (up to
      60 minutes), reaching statistical significance 15 minutes post-dose. In the
      titrated-dose study, the mean sum of PID (area under the PID vs time curve) at 30
      minutes post-dose was significantly greater with fentanyl sublingual than
      placebo, with significant improvements in PID seen at 10 minutes maintained at 60
      minutes post-dose. In the phase III study, patients receiving fentanyl sublingual
      were more satisfied with their treatment than patients receiving placebo
      (measured using the Patient Global Evaluation of Medication score), and almost
      half of all fentanyl sublingual recipients were satisfied or very satisfied with
      their treatment. Fentanyl sublingual was generally well tolerated in the two
      trials and most adverse events were mild to moderate in intensity.

PMID- 21080745
TI  - Olanzapine long-acting injection: a review of its use in the treatment of
      schizophrenia.
AB  - Olanzapine pamoate (olanzapine long-acting injection [OLAI]; Zypadhera(r);
      Zyprexa(r) RelprevvTM) is the intramuscular depot formulation of the atypical
      antipsychotic olanzapine. In two pivotal, double-blind clinical trials of 8 or 24
      weeks' duration, the efficacy of recommended dosages of OLAI injected every 2 or
      4 weeks (without oral supplementation) was greater than that of placebo in
      improving symptoms in acutely ill patients with schizophrenia, and generally
      similar to that of continuing oral olanzapine in preventing psychotic
      exacerbations in patients with schizophrenia whose symptoms had previously been
      stabilized on oral olanzapine. The effectiveness of OLAI in the maintenance
      treatment of schizophrenia was also demonstrated in an (ongoing) open-label
      extension study in which the all-cause discontinuation rate was 34.3% after 18
      months. OLAI is generally well tolerated. It has an adverse event profile similar
      to that of oral olanzapine, with the exception of adverse events related to the
      intramuscular route of administration; these include a manageable post-injection
      syndrome, which occurred in <0.1% of injections in clinical trials. The
      possibility of a post-injection syndrome event requires a risk management plan
      (RMP) to be adopted that includes observation by appropriately qualified
      personnel in a healthcare facility for at least 3 hours post-injection. With its
      potential to improve adherence to medication, and thereby treatment outcomes,
      OLAI is a useful addition to the pharmacological options available for the
      maintenance therapy of schizophrenia. Given its benefit/risk profile, OLAI
      appears most suited for patients who, despite responding well to oral olanzapine,
      have difficulties remaining adherent to this form of medication, provided they
      can comply with the conditions of the RMP.

PMID- 21080746
TI  - Efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen
      (Atripla(r)): a review of its use in the management of HIV infection.
AB  - The non-nucleoside reverse transcriptase inhibitor, efavirenz, and the two
      nucleoside reverse transcriptase inhibitors, emtricitabine and tenofovir
      disoproxil fumarate (tenofovir DF) are now available as a single-tablet regimen
      (efavirenz/emtricitabine/tenofovir DF 600 mg/200 mg/300 mg; Atripla(r)). The
      efavirenz/emtricitabine/tenofovir DF single-tablet regimen is the first once
      daily, single-tablet, triple antiretroviral therapy (ART) formulation available
      for the treatment of HIV infection and, in the EU, is indicated for use in adults
      infected with HIV-1 who have been virologically suppressed for >3 months on their
      current ART regimen. In treatment-experienced adults with HIV-1 infection already
      virologically suppressed with ART, switching to once-daily triple combination
      therapy with efavirenz, emtricitabine and tenofovir DF (including the single
      tablet regimen) is effective in maintaining virological suppression and is
      generally well tolerated, according to several randomized, open-label or
      noncomparative multicentre trials and an open-label extension study of up to 96
      weeks' duration. Moreover, additional data from some of these studies indicate
      that adherence to treatment was maintained or improved after switching to the
      once-daily triple combination, with patients generally preferring the
      efavirenz/emtricitabine/tenofovir DF single-tablet regimen over their previous
      more complex regimen and (in one of two trials) finding it easier to follow.
      Thus, the efavirenz/emtricitabine/tenofovir DF single-tablet regimen provides a
      convenient once-daily regimen for use in treatment-experienced adults that may
      confer an advantage over more complex or frequently administered regimens for
      which adherence to treatment is an issue.

PMID- 21080747
TI  - Optimizing the efficacy of first-line chemotherapy plus bevacizumab in metastatic
      colorectal cancer: analysis of multiple methods.
AB  - OBJECTIVE: To assess the efficacy and safety of first-line standard chemotherapy
      plus bevacizumab in metastatic colorectal cancer and to explore how to optimize
      therapeutic efficacy. DESIGN: First, meta-analysis and pooled analysis of three
      randomized, controlled trials were used to compare response rate (RR),
      progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse
      events (G3/4AEs) of chemotherapy plus bevacizumab (n = 1169) with those of
      chemotherapy alone (n = 1148). Second, using six different regimens plus
      bevacizumab, the Spearman method was used to analyze the correlation between
      these regimens and OS. Finally, one-way ANOVA was used to compare OS in these
      regimens. RESULTS: Overall, chemotherapy plus bevacizumab increased RR by 3.8%,
      prolonged PFS by 3.0 months and OS by 3.3 months, and increased G3/4AEs by 7.6%.
      Significant differences were found in PFS (hazard ratio [HR] = 0.65; p = 0.000),
      OS (HR = 0.79; p = 0.000), and G3/4AEs (risk ratio = 1.12; p = 0.006). However,
      no statistical difference was found in RR (odds ratio = 1.32; p = 0.17). The
      optimal regimens with regard to mean OS were capecitabine and irinotecan (CAPIRI)
      plus bevacizumab (24.00 months) and fluorouracil, leucovorin, and oxaliplatin
      (FOLFOX) plus bevacizumab (23.97 months). CONCLUSION: First-line standard
      chemotherapy plus bevacizumab conferred a significant improvement in OS. In
      combination with bevacizumab, both CAPIRI and FOLFOX are favorable regimens,
      though further studies are needed to confirm these results.

PMID- 21080748
TI  - Erlotinib resistance is altered after gemcitabine chemotherapy for recurrent non
      small-cell lung cancer.
AB  - We report the case of a male Mongolian lifelong non-smoker with recurrent non
      small-cell lung cancer (NSCLC) who developed resistance to the epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor erlotinib after initially
      responding to this agent but then subsequently had another response to a second
      course of erlotinib treatment after intervening gemcitabine chemotherapy. Sixteen
      months after the patient received chemoradiotherapy with gemcitabine/cisplatin
      plus radiotherapy, his recurrent mediastinal metastases were found to have
      progressed. Treatment with erlotinib was followed by an initial, partial response
      but evidence of progression was again observed 6 months later. The patient was
      then treated with gemcitabine chemotherapy, which resulted in a reduction in
      tumour volume. One month later, progression of mediastinal metastases was again
      observed and the patient received a second course of erlotinib. Another partial
      response occurred and the patient's disease remained stable at the 9-month follow
      up visit (and with no reported symptom progression at an 11-month telephone
      follow-up). Genetic examination of tumour tissue collected at the time of the
      original diagnosis and during the second course of erlotinib therapy revealed
      activating exon 19 mutation in the EGFR gene. This case suggests that resistance
      to erlotinib may change following chemotherapy and that repeat erlotinib therapy
      may be worth considering after chemotherapy in NSCLC patients who initially
      respond positively to erlotinib treatment but subsequently experience recurrence
      of disease.

PMID- 21080749
TI  - Elution of residual monomers from dental composite materials.
AB  - AIM: This study was designed to determine the type and amount of the monomers
      leached from the different particle sizes of the composite materials. MATERIALS
      AND METHODS: Three different disk sizes (2, 4, 6 mm) prepared for each material
      group (Filtek Flow, Filtek A110, Filtek P60 and Filtek Supreme) were polymerised
      by LED and halogen light; the specimens were then placed in artificial saliva.
      The monomer release in 30 min and 24 hrs from the specimens was analyzed in HPLC
      calibrated for the monomer extracts before. RESULTS: TEGDMA release was detected
      in all material groups after 30 min and after 24 hrs. BisGMA and BisEMA were not
      determined in any groups and UDMA was detected only in Filtek Supreme.
      Significant differences in release of TEGDMA and UDMA were obtained between the
      different sizes of discs. Significantly high amount of TEGDMA and UDMA monomer
      release was obtained in LED than Halogen groups. Lower amount of monomer release
      was obtained in species of 30 min than 24 hrs. CONCLUSION: Data has revealed that
      the monomer release could be detected significantly high from the composite
      materials polymerized by a lower output curing light device; and higher elution
      of monomers was determined as the composite thickness has increased. Therefore,
      the clinical applications of composite materials and the type of curing units
      have very important effects on the success of restorations and in the decrease of
      potential side effects.

PMID- 21080750
TI  - Relationship between mesiodistal crown diameters of permanent first molars and
      deciduous second molars.
AB  - AIM: To determine whether there is a relationship between the mesiodistal crown
      diameters of permanent first molars and deciduous second molars, and to update
      their odontometric values for the Spanish population. MATERIALS AND METHODS: A
      cross-sectional descriptive study was performed of a sample of molars in 101
      children (46 boys and 55 girls) of Spanish parents.The measurements were
      performed on cast dental models using a fine-tipped caliper with accuracy of +/-
      0.05 mm. RESULTS: Statistically significant differences were detected between
      sexes both for the permanent first molars and for the deciduous second molars.
      However, no differences were detected between antimeric teeth. The size of the
      deciduous second molars was related to the size of the permanent first molar, and
      this relationship was statistically significant. CONCLUSION: As a correlation was
      found between the mesiodistal crown diameters of permanent first molars and
      deciduous second molars, the findings of this study may be used as a predictive
      factor for tooth-jaw size disharmony, and therefore for possible crowding of the
      permanent dentition.

PMID- 21080751
TI  - Oral hygiene and periodontal treatment needs in children and adolescents with
      coeliac disease in Greece.
AB  - AIM: To evaluate the factors that influence the oral hygiene and the periodontal
      treatment needs of children and adolescents with coeliac disease (CD) in Greece.
      METHODS: The sample consisted of 35 children and adolescents, aged 4-18 years.
      The evaluation included consideration of the detailed medical history, the
      duration of CD and of gluten-free diet, the history of oral mucosal findings and
      a dental questionnaire that included information about oral hygiene habits,
      symptoms of periodontal disease and dental attendance. The clinical dental
      examination consisted of the simplified gingival index, the oral hygiene index
      and the periodontal screening and recording index. STATISTICS: The chi square and
      logistic regression analysis were performed in order to determine the factors or
      parameters that had a statistically significant (p <= 0.05) impact on oral
      hygiene and periodontal treatment needs of children and adolescents with CD.
      RESULTS: The periodontal treatment need of children and adolescents with CD were
      high and most of them needed treatment of gingivitis (60.01%) and only a few
      subjects had a healthy periodontium (34.29%). The periodontal treatment need
      index, the simplified gingival index and the hygiene index correlated
      statistically significantly with the presence of a coexisting disease, frequency
      of tooth brushing, bleeding upon brushing and oral malodor. CONCLUSION: The
      periodontal treatment need of children and adolescents with CD correlated with
      factors that related to the presence of a second medical condition and to the
      personal oral hygiene habits. Additionally, the oral hygiene level and
      periodontal status of children with CD do not have any specific characteristics
      but they have similarities to the oral hygiene level and periodontal status of
      the children of the general population.

PMID- 21080752
TI  - Comparative evaluation of microleakage of two self-etching dentin bonding agents
      on primary and permanent teeth. An in vitro study.
AB  - AIM: Conservative procedures using dentin bonding agents are one of the important
      aspects of paediatric dental practice. The objective of this in vitro study was
      to comparatively evaluate the microleakage of two self etching adhesives in
      primary and permanent teeth. MATERIALS AND METHODS: Sixty-four human anterior
      teeth (thirty-two primary and thirty-two permanent) were divided into four
      groups: primary teeth bonded using a 6th generation (Contax) bonding agent;
      permanent teeth bonded using a 6(th) generation (Contax) bonding agent; primary
      teeth bonded using a 7(th) generation (Clearfil S3) bonding agent; permanent
      teeth bonded using a 7(th) generation (Clearfil S3) bonding agent. A Class V
      cavity was prepared on all samples and were restored with composite resin as per
      manufacturers' instruction. After thermocycling, the teeth were stained with
      methylene blue, sectioned, and measured for microleakage. RESULTS: It was found a
      statistically significant difference in microleakage between incisal and gingival
      margins in each of the study group. CONCLUSION: Clearfil S3 (7(th) generation)
      bonding agent could be of greater advantage in paediatric dentistry than Contax
      (6(th) generation) because of its fewer steps and lesser microleakage in both
      primary and permanent teeth.

PMID- 21080753
TI  - Otitis media with effusion and dental occlusion: is there any relationship?
AB  - AIM: Auditory tube dysfunction is one of the aetiological causes of otitis media.
      Studies suggest a correlation between otitis media with effusion and dental
      malocclusion. Our goal was to determine any correlation between dental
      malocclusion and otitis media with effusion in children with chronic upper airway
      obstruction due to tonsil and adenoid enlargement. MATERIALS AND METHODS: This
      prospective study evaluated 52 children with otitis media with effusion and 48
      without, aged 4.2 to 10.8 years. A questionnaire was answered by the parents
      about breast or bottle-feeding and bad oral habits. Malocclusion was diagnosed
      according to Angle's classification for molar relationships in Classes I, II and
      III, posterior and anterior cross bite, open and deep bite, and overjet. RESULTS
      AND CONCLUSION: The results suggested no correlation between dental malocclusion
      and otitis media with effusion. Other potential confounders, such as breast or
      bottle- feeding and oral habits were also not correlated.

PMID- 21080754
TI  - An interdisciplinary approach to a survey on dental caries in a group of 3-year
      olds in Ascoli Piceno (Italy).
AB  - AIM: The purpose of this study was to investigate the dental caries experience in
      a group of 3-year-old children, through an interdisciplinary protocol, both
      paediatric and paedodontic, in the district of Ascoli Piceno (Marche, Italy).
      MATERIALS AND METHODS: A sample of 82 children, 38 males and 44 females, was
      recruited by four paediatricians during a preliminary study phase, which
      consisted of the epidemiological survey explanation to the involved children's
      parents and informed consents collection; the survey was first planned and then
      performed by one calibrated examiner, (Cohen k test was 0.85) in two days on May
      2008. The examinations were performed in the nurseries of the schools attended by
      the children. The collected data were analysed by descriptive and association
      statistics: the chi2 test was used to investigate the association between caries
      and gender, assuming as statistical significance level the p < 0.05 value.
      RESULTS: The study revealed that caries prevalence in the observed population was
      38%, while caries free group accounted for 61%; the mean dmft was 1.06, with a
      standard deviation of 1.64. No statistical significance was observed in the
      association between caries and gender (chi2=0.65, p > 0.05). discussion: Dental
      caries prevalence of the surveyed population, according to the WHO 2010
      objectives, was judged quite high, focusing the low caries free group (61%
      instead of 90% or over) and the children's preschool age; nonetheless the sample
      situation was not considered as critical, because the WHO 2000 goals were
      achieved (caries free > 50%). CONCLUSION: The interdisciplinary paedodontic
      paediatric protocol, used in the present study, was a useful and powerful
      instrument for preparing the epidemiological survey and could be the basis of
      future preventive programs.

PMID- 21080755
TI  - Effect of the Enveloppe Linguale Nocturne on atypical swallowing: surface
      electromyography and computerised postural test evaluation.
AB  - AIM: Swallowing is a neuromuscular mechanism regulated by many nervous reflex
      arcs. Persistence of child swallowing at the end of dental eruption is called
      atypical swallowing (AS). This condition is related to a dysfunction of vertical
      maxillary growth called open bite. The authors treated this malocclusion with the
      Enveloppe Linguale Nocturne (ELN), or tongue positioner, created by Dr. Bonnet.
      The aim of this work is to evaluate the effect of ELN on swallowing and the
      postural variation obtained by its use. MATERIALS AND METHODS: Seven patients
      affected by AS were evaluated. Surface Electromyography (sEMG) testing was
      performed on each patient with different tongue positions, and swallowing was
      evaluated with and without the ELN. A surface Electromyograph (Biopack) with 8
      channels was used (4 channels for the right muscles and 4 for the left) on 4
      groups of muscles: temporals, masseters (MM), submental (SUB) and
      sternocleidmastoids. On each patient a postural test using a computerised
      Postural test (Lizard) was also performed. Statistical analysis was done using
      the Graph pad Instat 3 both for sEMG activity and for computerised postural
      analysis. RESULTS: All seven subjects had different results in the sEMG and
      footrest tests. The sEMG test results indicated that muscle activation and
      swallowing duration varied greatly with the use of ELN, with a reduction of time
      of swallow act (p = 0.002) and variation in contraction of muscles. Mean MM
      activation was higher without ELN than in tests performed with the appliance (p =
      0.002). Mean SUB activation was higher with than without ELN (p = 0.0033). ELN
      has a therapeutic effect on posture too. Computerised postural test without
      device showed in all patients an alteration of barycentre as well as an elevated
      oscillatory record (A mmq; V mms). With ELN footrest kilogram difference (p =
      0.0110), Oscillatory Area (P = 0.0102) and velocity of oscillation (P = 0.0102)
      presented a great reduction in respect to patients record without ELN.
      CONCLUSION: With ELN the tongue reaches the physiologic position during the
      swallowing and it is possible to have a low dental contact without tongue
      interference. ELN has no dental retention or contact. For this reason sEMG
      swallowing test shows that ELN induces a Mm activation reduction compared to
      swallowing test without ELN (P = 0.002) and an increase of SUB activation (P =
      0.0033). In the same way with ELN there is a significant reduction of time of
      swallowing (c.f. oral phase) (P = 0.002). Patients with ELN changed their posture
      with a complete modification of barycentre (Footrest unbalancing kg P = 0.0110),
      oscillatory movement area (Footrest Area difference P = 0.0102), and oscillatory
      Velocity (Footrest Velocity oscillation difference P = 0.0102). These data
      suggest that this appliance has a function in the rehabilitation of atypical
      swallowing. ELN produces a physiologic neuromuscular mechanism that induces the
      correction of tongue position.

PMID- 21080756
TI  - Aicardi syndrome: a case report.
AB  - BACKGROUND: Aicardi Syndrome is an X-linked autosomal recessive neurodegenerative
      encephalopathy. The diagnostic triad is composed by infantile spasms, agenesis of
      corpus callosum and chorioretinal lacunae. Additional common findings are:
      microencephaly, spasticity and severe mental delay. It affects only females
      because of early embryonic lethality in males. A significant number of females
      with Aicardi syndrome are of normal birth and develop normally until three months
      of age when infantile seizures begin. Psychomotor retardation is usually severe,
      neuromotor retardation is commonly present with lack of motor and language
      skills. Literature reports only few information about the dentofacial features of
      the syndrome. CASE REPORT: We present the case of a patient, by describing the
      dental and facial characteristics with focus on dental prevention in order to
      avoid dental pain and the risks connected to general anaesthesia, and ultimately
      for improving the quality of life.

PMID- 21080757
TI  - Oral rehabilitation with endosseous implants in a child with ectodermal
      dysplasia: a case report.
AB  - AIM: The purpose of this article is to report the clinical course of a 12-year
      old child with ectodermal dysplasia who was treated with an implant-supported
      overdenture for the mandible and an overdenture for the maxilla. CASE REPORT: Two
      dental implants were placed in the canine regions of the mandible. The maxillary
      teeth were prepared for the milled copings. Because the preparation of parallel
      walls was difficult, near-parallelism with an angle of convergence or taper of
      approximately 5 degrees was achieved. The cervical third of the teeth was
      prepared to be as parallel as possible to one another. In addition, the occlusal
      surfaces were reduced 1.5 mm, and the axial surfaces were reduced 1 mm. Occlusal
      reduction was performed to provide adequate thickness for the overlying denture
      base material. A chamfer finish line was prepared. The copings were cast with a
      Cr-Ni-based metal alloy and luted, bilateral balanced occlusion was developed
      using anatomic acrylic teeth. An impression was taken with an individual tray for
      impressions of overdentures. In response to the patient's dry mucosa, the
      impressions were taken using rapid-setting silicone impression material with high
      elasticity. Bilateral balanced occlusion was achieved using anatomic acrylic
      teeth for overdentures. The maxillary overdenture and implant-supported
      mandibular overdenture were prepared by conventional methods using thermal-curing
      acrylic resin. The patient was seen 48 hours later for adjustment, then after 1
      and 2 weeks, 1, 3, and 6 months, and 1 year and he is still satisfied with his
      prosthesis both aesthetically and functionally. CONCLUSION: The use of endosseous
      implants in the prosthetic rehabilitation of children with ectodermal dysplasia
      may provide a considerable improvement in comparison with traditional prosthetic
      methods.

PMID- 21080758
TI  - Genomic evaluation during permeability of indomethacin and its solid dispersion.
AB  - Drug resistance was first identified in cancer cells that express proteins known
      as multidrug resistance proteins that extrude the therapeutic agents out of the
      cells resulting in alteration of pharmacokinetics, tissue distribution, and
      pharmacodynamics of drugs. To this end studies were carried out to investigate
      the role of pharmacological inhibitors and pharmaceutical excipients with a
      primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate
      holistic changes in transporter gene expression during permeability upon
      formulation of indomethacin as solid dispersion. Initial characterization studies
      of solid dispersion of indomethacin showed that the drug was dispersed within the
      carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers
      revealed that drug absorption increased by 4-fold when reformulated as solid
      dispersion. The last phase of the work involved investigation of gene expression
      changes of transporter genes during permeability. The results showed that there
      were significant differences in the expression of both ATP-binding cassette (ABC)
      transporter genes as well as solute carrier transporter (SLC) genes suggesting
      that the inclusion of polyethylene glycol as well as changes in molecular form of
      drug from crystalline to amorphous have a significant bearing on the expression
      of transporter network genes resulting in differences in drug permeability.

PMID- 21080761
TI  - Cardiovascular risks in HIV patients.

PMID- 21080762
TI  - Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion
      in the urine in patients with cirrhosis and water retention.
AB  - BACKGROUND: Terlipressin is a vasopressin analogue used for its potent V1a
      effects in cirrhotic patients. Recent data suggest that terlipressin has affinity
      to renal V2 receptors and modulates Aquaporin 2 (AQP2) expression and free water
      clearance. Stimulation of renal V2 receptors may also affect sodium transport via
      the Epithelial Sodium Channel (ENaC). Furthermore, endothelial V2 receptors may
      indirectly affect proximal sodium handling by increasing plasma cAMP. METHODS: We
      investigated 18 patients with cirrhosis and ascites before and after infusion of
      2 mg of terlipressin. Plasma cAMP and urine AQP2 were measured and a newly
      developed radioimmunoassay was used to quantify ENaC in the urine. RESULTS: Mean
      arterial blood pressure increased from 87 +/- 15 to 105 +/- 19 mmHg, p < 0.001
      after terlipressin infusion and GFR increased from 52 +/- 6 to 69 +/- 9 mL/min, p
      < 0.01. Urine-ENaC in ng/mmol creatinine increased from 42 +/- 6 to 50 +/- 7
      ng/mmol creatinine, p = 0.05. Urine sodium increased from 43 +/- 8 to 62 +/- 9
      mmol/L, p < 0.01. Plasma cAMP was not affected by terlipressin, 106 (63-673) vs.
      103.5 (69-774) pmol/mL, NS. The rise in ENaC excretion correlated with the rise
      in AQP2 excretion, r = 0.63, p < 0.01. There was a weak correlation between the
      change in MAP and the rise in AQP2 excretion (p < 0.05). CONCLUSIONS: Increased
      ENaC excretion suggests increased abundance of ENaC and resultant increased
      distal sodium reabsorption. The V2 effects of terlipressin are insufficient to
      stimulate the endothelial V2 receptors since plasma cAMP is unaltered. Despite
      pronounced V1a and some V2 effects of terlipressin, additional effects on
      proximal sodium handling are therefore not likely.

PMID- 21080763
TI  - Is my child sick? Parents' management of signs of illness and experiences of the
      medical encounter: parents of recurrently sick children urge for more
      cooperation.
AB  - OBJECTIVES: Parents of sick children frequently visit their general practitioners
      (GPs). The aim was to explore parents' interpretation of their child's incipient
      signs and symptoms when falling ill and their subsequent unsatisfactory
      experience with the GP in order to make suggestions for improvements in the
      medical encounter. DESIGN: Semi-structured interviews. SETTING AND SUBJECTS:
      Twenty strategically selected families with a child from a birth cohort in
      Frederiksborg County, Denmark were interviewed. RESULTS: Parents wanted to
      consult their GP at the right time, i.e. neither too early nor too late. Well
      educated parents experienced a discrepancy between their knowledge about their
      child, the information they had sought about the illness and the consultation
      with the GP, when they were dismissed with phrases such as "it will disappear" or
      "it is just a virus". The parents went along with the GP's advice if the child
      only occasionally became sick. However, parents of children with recurrent
      illnesses seemed very frustrated. During the course of several consultations with
      their GP, they started to question the GP's competence as the child did not
      regain health. CONCLUSIONS: Parents want to be acknowledged as competent
      collaborators. The GP's failure to acknowledge the parents' knowledge of their
      child's current illness, and the parents' attempt to identify what is wrong with
      the child and make the child feel better before the encounter may have
      consequences for the GP's credibility. It is therefore recommended that parents
      of children with recurrent illnesses receive extra attention and information.

PMID- 21080764
TI  - Dyes, trypanosomiasis and DNA: a historical and critical review.
AB  - Trypanosomiasis, a group of diseases including sleeping sickness in humans and
      Nagana in cattle in Africa, and Chagas' disease in South America, remains a
      considerable problem in the 21(st) century. The therapies that are available,
      however, usually have their roots in the "dye therapy" of a century ago,
      knowledge gained at the microscope from parasite staining procedures and
      converted to chemotherapy based on compounds closely related to the laboratory
      reagents. Dyes such as trypan red and trypan blue led to the development of
      suramin, while cationic nitrogen heterocyclic dyes furnished examples of the
      phenanthridinium class, such as ethidium (homidium) and isometamidium. Both
      suramin and isometamidium remain in use. Owing to mutagenicity issues, the
      presence of ethidium among the phenanthridinium dyes has led to concerns over the
      clinical use of related derivatives. There are several mechanisms for dye-DNA
      interaction, however, including possible hydrogen bonding of dye to the polymer,
      and these are discussed together with structure-activity relations and cellular
      localization of the phenanthridine and isomeric acridines involved. Better
      understanding of nucleic acid binding properties has allowed the preparation of
      more effective phenanthridinium analogues intended for use as
      anticancer/antiviral therapy.

PMID- 21080767
TI  - Risk factors for infections caused by multidrug-resistant bacteria in patients
      with solid tumours.
AB  - OBJECTIVES: We aimed to determine the risk factors for healthcare-associated
      infections (HCAI) caused by multidrug-resistant (MDR) bacteria in patients with
      solid tumours. METHODS: This retrospective study was performed in the Department
      of Clinical Microbiology and Infectious Diseases, Mersin Teaching and Research
      Medical Centre, between January 2004 and December 2008. SPSS version 11.5 program
      package was used for the statistical analyses. RESULTS: A total of 145 patients
      who had an HCAI were analyzed; 62% of the patients were male and their median age
      was 57.7 +/- 16 y and median Charlson co-morbidity score was 4.94 +/- 1.2. During
      the study period, 83 MDR bacteria were isolated from HCAIs that developed in 70
      (48.3%) patients. In multiple binary logistic regression analysis, duration of
      hospital stay (odds ratio (OR) 1.041, 95% confidence interval (CI) 1.007-1.077; p
      = 0.019), surgery (OR 3.115, 95% CI 1.288-7.535; p = 0.012), use of glycopeptides
      (OR 5.394, 95% CI 1.960-14.850; p = 0.001), and use of third-generation
      cephalosporins (OR 5.521, 95% CI 2.017-15.110; p = 0.001) were found to be
      independent risk factors for the development of an MDR infection. CONCLUSIONS:
      Among hospitalized patients with a solid tumour, HCAIs caused by MDR bacteria
      occurred more frequently in patients undergoing surgery, receiving third
      generation cephalosporins and glycopeptide antibiotics, and having a prolonged
      hospital stay.

PMID- 21080769
TI  - Forensic psychiatry: opportunities and future challenges. Introduction.

PMID- 21080770
TI  - Juveniles in court.
AB  - Nineteenth-century American reformers were concerned about the influence of
      immaturity and development in juvenile offenses. They responded to their
      delinquent youths through the creation of juvenile courts. This early American
      juvenile justice system sought to treat children as different from adults and to
      rehabilitate wayward youths through the state's assumption of a parental role.
      Although these rehabilitative goals were never fully realized, the field of
      American child psychiatry was spawned from these efforts on behalf of delinquent
      youths. Early child psychiatrists began by caring for juvenile offenders. The
      function of a child psychiatrist with juvenile delinquents expanded beyond
      strictly rehabilitation, however, as juvenile courts evolved to resemble criminal
      adult courts-due to landmark Supreme Court decisions and also juvenile
      legislation between 1966 and 1975. In response to dramatically increased juvenile
      violence and delinquency rates in the 1980s, juvenile justice became more
      retributional, and society was forced to confront issues such as capital
      punishment for juveniles, their transfer to adult courts, and their competency to
      stand trial. In the modern juvenile court, child psychiatrists are often asked to
      participate in the consideration of such issues because of their expertise in
      development. In that context we review the role of psychiatrists in assisting
      juvenile courts.

PMID- 21080771
TI  - Firearm laws: a primer for psychiatrists.
AB  - Persons with mental illness or substance abuse have been perceived by the public
      to pose an increased risk of violence to themselves and others. As a result,
      federal and state laws have restricted the right of certain categories of persons
      with mental illness or substance abuse to possess, register, license, retain, or
      carry a firearm. Clinicians should be familiar with the specific firearm statutes
      of their own states, which describe the disqualifying mental health/substance
      abuse history and the role and responsibility of the psychiatrist in the process.
      State statutes vary widely in terms of the definitions of, and reporting
      requirements relating to, prohibited persons with mental illness or substance
      abuse. States also vary in the duration of the prohibition and in the timing of
      the appeals process. Some of the statutes have specific provisions for the
      removal of a firearm when a prohibited person is identified. States may maintain
      a mental health database that is used to determine firearm eligibility and may
      forward information to the National Instant Criminal Background Check System. The
      National Instant Criminal Background Check System Improvement Amendments Act of
      2007 will likely increase the number of persons identified as belonging to the
      prohibited class.

PMID- 21080772
TI  - Disability and occupational assessment: objective diagnosis and quantitative
      impairment rating.
AB  - Industrial insurance originated in Europe in the nineteenth century and replaced
      the old system of negligence liability in the United States between 1910 and
      1940. Today psychiatric disability assessments are performed by psychiatrists in
      the context of Social Security Disability Insurance applications, workers'
      compensation claims, private disability insurance claims, and fitness for duty
      evaluations. Expertise in the performance of psychiatric disability evaluations
      is required, but general psychiatric residency programs provide experience only
      with treatment evaluations, which differ fundamentally from independent medical
      evaluations as to role boundaries and the focus of assessment. Psychiatrists
      offer opinions regarding psychiatric impairments, but administrative or judicial
      tribunals make the actual determinations of disability. Social Security
      Disability Insurance evaluations and workers' compensation evaluations are
      discussed, as is the distinction between diagnoses, which are categorical, and
      impairment ratings, which are dimensional. Inconsistency in impairment ratings
      has been problematic in the United States and elsewhere in the workers'
      compensation arena. A protocol for achieving more consistent impairment ratings
      is proposed, one that correlates three commonly used global rating scales in a 3
      * 5 grid, supplemented by objective psychological test data.

PMID- 21080773
TI  - Beyond emergencies: the use of physical restraints in medical and psychiatric
      settings.
AB  - Physical restraints, such as locked-door seclusion and two- or four-point leather
      restraints, are frequently used in both the medical and psychiatric settings.
      Efforts are currently under way to reduce the use of physical restraints in
      psychiatric settings; various institutional, state, and federal policies are
      place. However, using these same restraints in the context of providing medical
      care for psychiatric patients is more complicated, as it is uncertain which
      principles and regulations apply in a particular setting. For example, is the
      restraint governed by the policies that regulate the psychiatric application of
      restraints, by those that regulate the medical application of restraints, or by
      both? This article reviews the principles and regulations governing the use of
      restraints on psychiatric patients, with specific attention to the use of
      restraints in providing medical treatment to that patient population. Also
      addressed are general principles of risk management to help avoid negative
      outcomes and to reduce the risk of litigation for unauthorized or unlawful
      restraint. A case example is used to illustrate these concepts.

PMID- 21080775
TI  - Terrorism and the behavioral sciences.
AB  - Terrorism has existed for millennia and is a phenomenon well-known to many parts
      of the world. Americans were forced to recognize this phenomenon, and our
      vulnerability to it, by two sets of events in 2001: the attacks on New York City
      and Washington, DC, and the anthrax mailings that followed shortly thereafter.
      Psychiatry, psychology, and other behavioral and social sciences have been looked
      to for assistance in collecting and analyzing intelligence data, understanding
      terrorism, and developing strategies to combat terrorism. In addition to
      reviewing areas in which the behavioral sciences have made contributions in
      addressing this problem, this article discusses the developing roles for
      behavioral scientists in this field.

PMID- 21080774
TI  - The management of sex offenders: perspectives for psychiatry.
AB  - In the effort to identify and manage sex offenders, the differences between legal
      and medical/psychiatric terminology and approaches are readily apparent. This
      article discusses the different definitions and approaches of the two fields and
      considers both the behaviors that create risk to others and the strategies for
      reducing that risk. Particular attention is paid to the subcategory of paraphilic
      sex offenders. Treatment goals, modalities, and efficacies are discussed, as are
      evolving legal strategies for risk control and the need for interaction between
      law and medicine/psychiatry in order to accomplish common goals of risk
      management.

PMID- 21080778
TI  - Executive functions and aphasia treatment outcomes: data from an ortho
      phonological cueing therapy for anomia in Chinese.
AB  - This study examined the existence of a possible relationship between anomic
      treatment outcomes and executive functions. An ortho-phonological cueing method
      was used to facilitate object naming in 12 Cantonese-speaking anomic individuals.
      Treatment effectiveness for each participant was quantified and correlated with
      the performance of executive functions and language tasks. It was found that 10
      participants showed significant improvement in naming treated items. Eight of the
      participants were able to maintain treatment gains for at least 1 month.
      Phonological generalization effects were observed in two participants.
      Performance on the Test of Nonverbal Intelligence (TONI-3) was significantly
      correlated with effect sizes of treatment, treatment generalization and
      maintenance and the Attention Network Test (ANT) was significantly correlated
      with phonological generalization. The result of a simultaneous multiple
      regression suggested that the performance of the ANT played an important role in
      phonological generalization. The findings reinforce the current view about the
      role of executive functions in language rehabilitation. They also shed light on
      the effect of inhibitory control on treatment generalization.

PMID- 21080779
TI  - Anti-allergic effects of sinomenine by inhibition of prostaglandin D2 and
      leukotriene C4 in mouse bone marrow-derived mast cells.
AB  - Sinomenine is an alkaloid compound and a prominent anti-allergic agent found in
      the root of the climbing plant Sinomenium acutum. However, its effects on the
      bone marrow-derived mast cell (BMMC) mediated allergy and inflammation mechanism
      remain unknown. In this study, the biological effects of sinomenine were
      evaluated while focusing on its effects on the allergic mediator in PMA plus
      A23187-stimulated BMMCs. An investigation was also conducted to determine its
      effects on the production of several allergic mediators including interleukin-6
      (IL-6), prostaglandin D(2) (PGD(2)), leukotriene C(4) (LTC(4)), beta
      Hexosaminidase (beta-Hex), and cyclooxygenase-2 (COX-2) protein. The results
      revealed that sinomenine inhibited the PMA plus A23187-induced production of IL
      6, PGD(2), LTC(4), beta-Hex, and COX-2 protein. Taken together, these findings
      indicate that sinomenine has the potential for use in the treatment of allergy.

PMID- 21080782
TI  - Dose-dependent in-vivo toxicity assessment of silver nanoparticle in Wistar rats.
AB  - This study aims to suggest the limits of silver nanoparticle (AgNP) uses for
      medicinal purpose and was performed to explore the effect of various doses of
      silver nanoparticle in rats. Four different doses of AgNP (4, 10, 20, and 40
      mg/kg) were injected intravenously. For safety evaluation of injected AgNP, body
      weight, organ coefficient, whole blood count, and biochemistry panel assay for
      liver function enzyme (AST, ALT, ALP, and GGTP), comet assay, ROS, and
      histological parameter were performed; 10-12 week old animals were randomly
      divided into groups of six individuals each for control, and doses of 40, 20, 10,
      and 4 mg/kg AgNP injected. Significant changes were observed (p < 0.01) in
      hematological parameters (WBC count, platelets counts, haemoglobin, and RBC
      count) in the 40 and 20 mg/kg groups. The changes were non-significant in the
      other groups (4 and 10 mg/kg group). In the 40 mg/kg group, a significant
      increase was also found in liver function enzymes like ALT and AST (p < 0.01),
      ALP (p < 0.01), GGTP (p < 0.01), and bilirubin (p < 0.01). ROS in blood serum
      increased in the high dose group. Tail migration in single cell gel
      electrophoresis in the 40, 20, 10, 4 mg/kg, and control groups was 34.9, 29.5,
      17.8, 5.8, and 0.0 um, respectively, which indicated damage in the DNA strand in
      the high dose group. EDXRF showed a ~ 10-times increase in silver concentration
      in the 40 mg/kg group and TEM image also showed particle deposition in the 40
      mg/kg group. This study indicates that the AgNP in doses (< 10 mg/kg) is safe for
      biomedical application and has no side-effects, but its high dose (> 20 mg/kg) is
      toxic.

PMID- 21080783
TI  - A bovine herpesvirus type 1 mutant virus with truncated glycoprotein E
      cytoplasmic tail has defective anterograde neuronal transport in rabbit dorsal
      root ganglia primary neuronal cultures in a microfluidic chamber system.
AB  - Bovine herpesvirus type 1 (BHV-1) is an important component of the bovine
      respiratory disease complex (BRDC) in cattle. Following primary intranasal and
      ocular infection of cattle, BHV-1 establishes lifelong latent infection in
      trigeminal ganglia (TG). Upon reactivation from latency, the virus is transported
      from neuronal cell bodies in the TG to projected nerve endings in nose and cornea
      of latently infected cattle where the virus shedding occurs. This property of BHV
      1 plays a significant role in the pathogenesis of BRDC and maintenance of BHV-1
      in the cattle population. Recently, we have reported that a glycoprotein E (gE)
      cytoplasmic tail-truncated BHV-1 (BHV-1 gEAm453) did not reactivate from latency
      and was not shed in the nasal and ocular secretions of calves and rabbits. Here
      we describe the methods to establish rabbit primary dorsal root ganglia (DRG)
      neuron cultures in a microfluidic chamber system and to characterize in vitro
      anterograde and retrograde axonal transport properties of BHV-1 gE-deleted and
      BHV-1 cytoplasmic tail-truncated gEAm453 mutant viruses relative to BHV-1 gEAm453
      rescued/wild-type viruses. The results clearly demonstrated that whereas the BHV
      1 gE-deleted, BHV-1 gEAm453, and BHV-1 gEAm453-rescued/wild-type viruses were
      transported equally efficiently in the retrograde direction, only the BHV-1
      gEAm453-rescued/wild-type virus was transported anterogradely. Therefore, we have
      concluded that sequences within the BHV-1 gE cytoplasmic tail are essential for
      anterograde axonal transport and that primary rabbit DRG neuronal cultures in the
      microfluidic chambers are suitable for BHV-1 neuronal transport studies.

PMID- 21080784
TI  - The impact of early powered mobility on parental stress, negative emotions, and
      family social interactions.
AB  - Powered mobility has been found to have positive effects on young children with
      severe physical disabilities, but the impact on the family has been less well
      documented. We evaluated the impact of early powered mobility on parental stress,
      negative emotions, perceived social interactions, and parental satisfaction with
      wheelchair characteristics such as size and durability. The participants were
      parents of 23 children with disabilities-10 with orthopedic disabilities (average
      age 30.1 months) and 13 with cerebral palsy (average age 47.0 months). Pretest
      assessments were completed two times: at initial wheelchair evaluation and at
      wheelchair delivery. A posttest assessment was completed after each child had
      used the wheelchair for 4-6 months. Parents reported a lower perceived level of
      stress at the time of wheelchair delivery, although the magnitude of this effect
      was fairly small, standardized mean difference (delta) = .27. They also reported
      an increased satisfaction with their child's social and play skills (delta =
      .38), ability to go where desired (delta = .86), sleep/wake pattern (delta =
      .61), and belief that the general public accepts their child (delta = .39) after
      several months using the wheelchair. Parents reported an increase in interactions
      within the family at the time of wheelchair delivery (delta = .66). There was no
      decrease in negative emotions. Parents were satisfied with most factors relating
      to the wheelchair itself, with areas of concern being wheelchair size and
      difficulty adjusting the wheelchair. The findings suggest that self-initiated
      powered mobility for a young child had a positive impact on the family.

PMID- 21080780
TI  - Drug-eluting versus bare-metal stents in large coronary arteries.
AB  - BACKGROUND: Recent data have suggested that patients with coronary disease in
      large arteries are at increased risk for late cardiac events after percutaneous
      intervention with first-generation drug-eluting stents, as compared with bare
      metal stents. We sought to confirm this observation and to assess whether this
      increase in risk was also seen with second-generation drug-eluting stents.
      METHODS: We randomly assigned 2314 patients needing stents that were 3.0 mm or
      more in diameter to receive sirolimus-eluting, everolimus-eluting, or bare-metal
      stents. The primary end point was the composite of death from cardiac causes or
      nonfatal myocardial infarction at 2 years. Late events (occurring during months 7
      to 24) and target-vessel revascularization were the main secondary end points.
      RESULTS: The rates of the primary end point were 2.6% among patients receiving
      sirolimus-eluting stents, 3.2% among those receiving everolimus-eluting stents,
      and 4.8% among those receiving bare-metal stents, with no significant differences
      between patients receiving either drug-eluting stent and those receiving bare
      metal stents. There were also no significant between-group differences in the
      rate of late events or in the rate of death, myocardial infarction, or stent
      thrombosis. Rates of target-vessel revascularization for reasons unrelated to
      myocardial infarction were 3.7% among patients receiving sirolimus-eluting
      stents, 3.1% among those receiving everolimus-eluting stents, and 8.9% among
      those receiving bare-metal stents. The rate of target-vessel revascularization
      was significantly reduced among patients receiving either drug-eluting stent, as
      compared with a bare-metal stent, with no significant difference between the two
      types of drug-eluting stents. CONCLUSIONS: In patients requiring stenting of
      large coronary arteries, no significant differences were found among sirolimus
      eluting, everolimus-eluting, and bare-metal stents with respect to the rate of
      death or myocardial infarction. With the two drug-eluting stents, similar
      reductions in rates of target-vessel revascularization were seen. (Funded by the
      Basel Cardiovascular Research Foundation and the Swiss National Foundation for
      Research; Current Controlled Trials number, ISRCTN72444640.).

PMID- 21080785
TI  - Three-dimensional measurement of bone loss at implants in patients with
      periodontal disease.
AB  - BACKGROUND: The aim of this prospective study is to evaluate the three
      dimensional marginal bone level around implants 5 to 15 years after loading in
      partially edentulous patients treated for generalized chronic periodontitis (GCP)
      and generalized aggressive periodontitis (GAgP). METHODS: Seventeen patients with
      GCP and 17 patients with GAgP were treated with a total of 119 implants. Patients
      were examined clinically on a 3-month recall schedule after insertion of the
      superstructure, and radiographs were taken at fixed intervals. At the end of the
      observation period, cone-beam computed tomography was used for the analysis of
      the circumferential three-dimensional bone level (mesial, distal, buccal, and
      lingual/palatal) and determination of keratinized mucosa thickness (KMT).
      RESULTS: In both groups, a significant bone loss at implants was observed
      buccally (GAgP group: 4.49 +/- 2.93 mm; GCP group: 3.57 +/- 2.94 mm) with
      significantly more average bone loss in patients with GAgP (3.00 +/- 1.67 mm)
      compared to in patients with GCP (2.45 +/- 1.08 mm). The lowest values for KMT in
      both groups were found in the anterior mandible (GAgP group: 0.99 +/- 1.13 mm;
      GCP group: 0.82 +/- 0.91 mm). There were significant correlations between
      clinical parameters and bone loss in mandibles of patients with GAgP.
      CONCLUSIONS: The lowest value for KMT in both groups was found in the mandible.
      Bone loss was observed buccally and was more pronounced in patients with GAgP,
      with a significant correlation with keratinized mucosa and increased
      inflammation.

PMID- 21080786
TI  - Biologic interaction of three-dimensional periodontal fibroblast spheroids with
      collagen-based and synthetic membranes.
AB  - BACKGROUND: Cell-based therapy using autologous cells has been suggested as a
      potential approach for periodontal tissue regeneration. Spheroid systems are a
      form of three-dimensional cell culture that promotes cell matrix interaction,
      which could recapitulate the aspect of cell homeostasis in vivo. The aim of this
      study is to assess the interaction of periodontal fibroblast spheroids with
      synthetic and collagen-based membranes that have been used in guided tissue
      regeneration. METHODS: Commercially available normal human periodontal ligament
      fibroblasts were grown in spheroid forms using a liquid overlay technique and
      then transplanted onto a collagen-based and a polyglycolic acid-based membrane.
      The biologic interaction of the spheroids with the membranes was assessed using
      basic histology, Alamar blue tissue viability assay, scanning electron
      microscopy, and immunohistochemical analysis. RESULTS: Periodontal fibroblast
      spheroids adhered to both membranes, and the cells were able to proliferate and
      migrate from the spheroids both horizontally and vertically into the membrane
      scaffolds. Immunohistochemical analysis showed expression of collagen type I,
      periostin, and Runx2 by the periodontal fibroblasts. CONCLUSION: Periodontal
      fibroblast spheroids were able to grow three-dimensionally on the biologic
      membranes and may have the potential to be used together with guided tissue
      regeneration approaches as an adjunct for periodontal regeneration.

PMID- 21080787
TI  - Use of anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (P-15)
      in the treatment isolated Class I gingival recession of defects: a pilot study.
AB  - BACKGROUND: This study clinically evaluates the treatment outcome of coronally
      positioned flap (CPF) associated with anorganic bone mineral/peptide-15 (ABM/P
      15) in terms of root coverage and gain in clinical attachment level (CAL) and
      bone height (BH) in isolated Class I gingival recession (GR) defects. METHODS:
      Fifteen healthy subjects with bilateral and comparable Miller Class I GR defects
      were selected. The defects were randomly assigned either to the test group (CPF
      with ABM/P-15) or to the control group (CPF only). RESULTS: Six months after
      surgery, a reduction in GR was observed in the test and control groups (2.20 +/-
      0.54 and 2.40 +/- 0.80 mm, respectively; P <0.001) with no intergroup difference
      (P = 0.33). Complete root coverage was obtained in 10 and 11 defects in the test
      and control groups, respectively. In the test group 85.56% +/- 21.69% and in the
      control group 90.00% +/- 18.42% of the exposed root was covered. Although not
      clinically significant, a statistically greater increase in the gingival
      thickness was observed in the test group (0.03 mm; P = 0.01). CAL gain was
      significant in both groups (test group, 1.93 +/- 0.44 mm; control group, 2.13 +/-
      1.15 mm; P <0.001) with no intergroup difference (P = 0.42). Intergroup and
      intragroup differences in width of keratinized tissue and BH were not significant
      (P >=0.16). In the test group, a positive correlation was observed between BH at
      baseline and the reduction in GR (r = 0.56; P = 0.03). CONCLUSIONS: In isolated
      Class I GR defects, CPF associated with ABM/P-15 provided no significant
      difference in root coverage and CAL gain compared to CPF alone. In the ABM/P-15
      group, a greater reduction in GR was associated with higher bone level at
      baseline.

PMID- 21080788
TI  - 120 infrabony defects treated with regenerative therapy: long-term results.
AB  - BACKGROUND: The aim of this study is to evaluate the long-term benefits of
      regenerative therapy and which factors (i.e., smoking, oral hygiene, radiographic
      angle, tooth, clinical center, and biomaterial) influence results. METHODS: A
      total of 120 infrabony defects were treated with guided tissue regeneration using
      bioabsorbable and non-resorbable membranes with grafts or enamel matrix
      derivative (EMD) proteins. At baseline, smoking, x-ray angle, probing depth (PD),
      recession, and clinical attachment level (CAL) were recorded. CAL was measured 1
      year post-surgery and every 2 years for <=16 years. The participation of patients
      in oral hygiene protocols was recorded. RESULTS: The mean +/- SD baseline CAL was
      8.5 +/- 2.3 mm, baseline PD was 7.8 +/- 2.1 mm, and baseline x-ray angle was 31.8
      degrees  +/- 8.9 degrees . One year post-surgery, CAL gain was 4.1 +/- 2.1 mm.
      EMD was used in 47 defects, bioabsorbable membranes with deproteinized bovine
      bone were used in 41 cases, non-resorbable membranes were used in seven defects,
      bioabsorbable membranes and autogenous bone were used in five defects, and a
      combination was used in 20 defects. A total of 10% of subjects were smokers, and
      20% of subjects did not participate in an oral hygiene program. The average
      follow-up was 9 years. A total of 90% teeth survival was achieved at 13 years,
      and CAL gain was maintained at 82% for 11 years. Statistical analyses
      demonstrated that smoking and oral hygiene maintenance influenced long-term
      outcomes. The x-ray angle, tooth, clinical center, and biomaterials did not
      influence results. CONCLUSIONS: Regenerative therapy provided a high percentage
      of long-term success. Smoking and non-participation in oral hygiene maintenance
      negatively influenced the prognosis, whereas other factors did not affect long
      term results.

PMID- 21080789
TI  - Refractory periodontitis population characterized by a hyperactive oral
      neutrophil phenotype.
AB  - BACKGROUND: Neutrophils, in addition to being the primary protective component of
      the innate immune system, also contribute to periodontal destruction through
      production of reactive oxygen species (ROS), which cause damage to connective
      tissues and extracellular matrix after neutrophil activation. We have previously
      shown that hyperactive neutrophils are present in peripheral blood samples of
      patients diagnosed with refractory periodontitis. To test the hypothesis that
      oral neutrophil hyperactivity is related to periodontal disease severity, we used
      a flow cytometric approach to isolate and analyze oral neutrophil ROS (oROS)
      production in a refractory periodontal disease patient population. METHODS: Oral
      rinse samples and venous blood were obtained from 13 patients diagnosed with
      refractory periodontitis. After isolation of neutrophils from both samples,
      dihydrorhodamine 123 was used as a fluorescent probe for phorbol 12-myristate 13
      acetate-mediated ROS production as assessed through flow cytometry. For each
      patient, oROS production levels were expressed as a percentage of their baseline
      to maximal peripheral blood neutrophil ROS production range. RESULTS: Two
      distinct groups of refractory patients were identified based on levels of phorbol
      12-myristate 13-acetate-stimulated oROS production. The patient group with high
      oROS production had significantly more clinical attachment loss (AL) compared to
      the patient group with low oROS production. CONCLUSIONS: Our findings demonstrate
      that a group of refractory patients with increased clinical AL present a
      hyperactive oral neutrophil phenotype characterized by increased potential for
      ROS production. Identification of this exaggerated oral neutrophil phenotype
      could allow clinicians to identify which patients are more susceptible to rapid
      disease progression.

PMID- 21080791
TI  - Estrogen-free oral hormonal contraception: benefits of the progestin-only pill.
AB  - Although combined oral contraceptives (COCs) are commonly used and highly
      effective in preventing pregnancy, they may not be suitable for some women. COC
      use is associated with increased rates of cardiovascular events and is not
      recommended in nonbreastfeeding women in the immediate postpartum period or in
      breastfeeding women during the initial 6 months of breastfeeding. Moreover,
      estrogen-related adverse effects, such as headache, are common. Estrogen-free
      progestin-only pills (POPs) are a valuable option in women who prefer to take an
      oral hormonal contraceptive, but are ineligible for, or choose not to use, COCs.
      Although some POPs have been associated with lower contraceptive effectiveness
      than COCs, the POP containing desogestrel has shown similar contraceptive
      effectiveness to COCs. The most commonly reported complaints in women using all
      POPs are bleeding problems. Counseling women interested in using POPs about the
      variable bleeding patterns associated with this method may improve compliance and
      acceptance.

PMID- 21080790
TI  - Levels of pentraxin-3 in gingival crevicular fluid and plasma in periodontal
      health and disease.
AB  - BACKGROUND: Pentraxins are classic mediators of inflammation and markers of acute
      phase reactions. Pentraxin-3 (PTX3) is the first-identified long pentraxin and is
      believed to be a true independent indicator of disease activity. Although a
      classic pentraxin, C-reactive protein, and its association with various systemic
      diseases is well documented in the periodontal literature, there is no data on
      PTX3 to our knowledge. METHODS: Forty participants (20 males and 20 females; age
      range: 23 to 50 years) were involved in the study. Participants were divided into
      three groups based on gingival index, probing depth, and clinical attachment
      level: the healthy group (group 1; n = 10), gingivitis group (group 2; n = 15),
      and periodontitis group (group 3; n = 15). Gingival crevicular fluid (GCF) and
      plasma samples collected from each subject were quantified for PTX3 levels using
      an enzyme-linked immunosorbent assay. RESULTS: In tandem with the disease
      progression from healthy to gingivitis to periodontitis, the mean PTX3
      concentrations increased in GCF and plasma. However, GCF values were higher than
      plasma values. It was found that PTX3 concentration was highest in group 3 and
      lowest in group 1. PTX3 concentrations also correlated positively with
      periodontal parameters. CONCLUSIONS: GCF and plasma PTX3 concentrations
      correlated positively in all groups. However, within the limits of the present
      study, the differences in plasma PTX3 levels were not found to be statistically
      significant. Hence, GCF PTX3 values were considered a marker of inflammatory
      activity in periodontal disease. However, PTX3 deserves further consideration as
      a therapeutic target. Additional large-scale studies should be carried out to
      confirm positive correlations.

PMID- 21080792
TI  - Neuro-oncology, a decade of temozolomide and beyond.

PMID- 21080793
TI  - The USA's healthcare reform: the cost of prescription medicines.

PMID- 21080794
TI  - When adult cancers occur in children.

PMID- 21080796
TI  - Advances and trends in dermato-oncology.
AB  - The 6th Congress of the European Association of Dermato-Oncology, held in Athens,
      Greece (16-19 June 2010), focused on the most recent advances in the field of
      melanoma, epithelial skin cancers and other malignant skin tumors. Under the
      theme 'transforming care through personalized medicine', the scientific program
      reviewed and discussed the significant changes that are currently taking place in
      many aspects of skin cancer care, from risk prediction and prevention to the use
      of targeted treatments. This article highlights the key messages from selected
      presentations that feature the remarkable progress in our understanding of the
      pathogenesis of skin malignancies and the rapid 'translation' of this knowledge
      into new effective treatments in clinical practice.

PMID- 21080797
TI  - Ipilimumab: attenuation of an inhibitory immune checkpoint improves survival in
      metastatic melanoma.
AB  - Evaluation of: Hodi FS, O'Day SJ, McDermott DF et al. Improved survival with
      ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363(8), 711-723
      (2010). Interference with the inhibitory immune regulatory checkpoints that act
      to constrain overly exuberant immune responses and help to maintain peripheral
      tolerance represents an exciting new paradigm in tumor immunotherapy. We review
      the study of Hodi and colleagues evaluating the role of blockade of one of these
      pathways (cytotoxic T-lymphocyte antigen-4) with a monoclonal antibody
      (ipilimumab, developed by Medarex, NJ, USA and Bristol-Myers Squibb, NY, USA) in
      patients with advanced melanoma who had failed prior treatments. The randomized
      Phase III study demonstrates superior overall survival in patients receiving
      ipilimumab, either alone or in combination with a gp100 peptide vaccine, compared
      with those receiving the vaccine alone. The results represent the first positive
      randomized clinical trial ever reported in patients with metastatic melanoma in
      terms of overall survival, the first showing a beneficial effect of a melanoma
      treatment in the second-line setting, and the first demonstration that blockade
      of an immune-inhibitory pathway can be an effective cancer therapeutic.

PMID- 21080798
TI  - Metastatic retropharyngeal lymph nodes in nasopharyngeal carcinoma: imaging
      criteria.
AB  - Evaluation of: Zhang GY, Liu LZ, Wei WH, Deng YM, Li YZ, Liu XW. Radiologic
      criteria of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma
      treated with radiation therapy. Radiology 255(2), 605-612 (2010). Nasopharyngeal
      carcinoma (NPC) is the most common nasopharyngeal neoplasm and has a high
      propensity for developing regional neck adenopathy. NPC arises most often in the
      fossa of Rosenmuller, and differs significantly from other head and neck cancers
      with respect to its incidence, etiology, clinical behavior and treatment. NPC is
      commonly associated with retropharyngeal nodes. As retropharyngeal nodes are
      anatomically difficult to approach for biopsy/fine-needle aspiration cytology,
      imaging plays a critical role in their detection and staging. The paper by Zhang
      et al. reports data on 303 NPC patients from a large center in China and
      highlights specific radiologic criteria for assessing retropharyngeal nodal
      metastases in nasopharyngeal carcinoma.

PMID- 21080799
TI  - Predicting and preventing melanoma invasiveness: advances in clarifying E2F1
      function.
AB  - Malignant melanoma of the skin is one of the most aggressive human cancers with
      increasing incidence, despite efforts to improve primary prevention. In
      particular, the prognosis of patients at late stages of the disease has not
      significantly improved in the last three decades, because systemic therapies have
      proven disappointing. Thus, metastatic melanoma continues to be a daunting
      clinical problem. The increasingly high rates of lethal outcome associated with
      advanced melanoma rely on the acquisition of invasiveness, early metastatic
      dissemination of tumor cells from their primary sites, and generation of
      chemoresistance as a consequence of alteration of key molecules involved in the
      regulation of cell survival. Thus far, extensive studies have been conducted to
      understand the molecular mechanisms that drive tumor progression, but the
      specific requirements underlying the aggressive behavior are still widely
      unknown. Understanding the determinants of this process is key to unveiling its
      dynamics, especially those that promote invasiveness, and may open new routes for
      the development of therapeutic strategies that control metastatic spread, and
      eventually the prevention of life-threatening metastases. Here, we review recent
      advances on molecular aspects, particularly of E2F1 transcription factor
      function, in the context of patient data, and discuss the implications for
      targeting melanoma cells when they begin to invade and metastasize.

PMID- 21080800
TI  - Burden of metastatic bone disease from genitourinary malignancies.
AB  - Bone metastases are common among patients with stage IV genitourinary cancers.
      Most patients with bone metastases develop at least one debilitating and
      potentially life-limiting skeletal-related event. These events are associated
      with increased medical expenses and decreased quality of life. Current guidelines
      recommend screening for bone metastases in men with high-risk prostate cancer,
      but guidance for screening and treatment of bone metastases from genitourinary
      cancers varies by country and setting. Several bisphosphonates have been
      evaluated in the advanced genitourinary cancer setting. Zoledronic acid has
      demonstrated efficacy in significantly reducing the risk of skeletal-related
      events in patients with bone metastases from a broad range of solid tumors
      including prostate, renal and bladder cancers, and is recommended for preserving
      bone health.

PMID- 21080801
TI  - Current and emerging molecular targets in glioma.
AB  - Gliomas are the most common and lethal neurological cancers. Despite research
      efforts, the prognosis for patients with malignant gliomas remains poor. Advances
      in the understanding of cellular and molecular alterations in gliomas have led to
      the emergence of experimental molecularly targeted therapies. This article
      summarizes recent progress in the development of targeted therapies for glioma,
      focusing on emerging molecular targets, including neuropeptide and neurotrophin
      pathways, glutamate receptors, epigenetic mechanisms and glioma stem cell
      targets. Recent clinical trials of small molecules and antibodies targeted at
      growth factor pathways and intracellular signaling cascades are also discussed.

PMID- 21080802
TI  - Potential role of miRNAs and their inhibitors in glioma treatment.
AB  - Recent years have seen an intense period of research on the functions of miRNAs,
      recently discovered key regulators of gene expression that act through
      suppression of translation of target mRNAs. Several hundred miRNAs have been
      identified in humans, and these show characteristic expression patterns,
      depending on tissue type, cell type or environmental stimuli. Like other types of
      cancer, the brain tumor glioblastoma shows a distinct miRNA expression signature,
      and a number of recent studies have linked these miRNA alterations to key
      hallmarks of glioblastoma including proliferation, survival, invasion,
      angiogenesis and stem cell-like behavior. These studies have opened the door to
      the possibility of utilizing miRNAs or miRNA antagonists as therapeutic agents
      for the treatment of brain tumors.

PMID- 21080803
TI  - Therapy and prophylaxis of brain metastases.
AB  - Metastases of various tumors to the brain account for the majority of brain
      cancers, and are associated with a poor prognosis. The most common primary sites
      are lung, breast, skin, kidney and colon; 10-40% of cancer patients develop brain
      metastases during the course of the disease. The incidence of brain metastasis
      appears to be rising; reasons may include better therapies for the systemic
      disease with longer survival of cancer patients but lower efficiency against
      brain metastases. In this article, we will discuss the conventional treatment
      with surgery, radiosurgery, radiotherapy and chemotherapy, but also new
      directions in the management of solid brain metastases. While general therapeutic
      nihilism should be avoided, it is important to recognize that the number of brain
      metastases, the extent of the systemic disease and also the tumor type have to be
      taken into account when choosing individual treatment regimens. Finally, special
      emphasis will be put on established and future approaches to prevent the disease.
      We thus aim to provide a framework for treating patients with different
      presentations of brain metastases, and to highlight important avenues for
      research.

PMID- 21080804
TI  - Interventions for cognitive deficits in patients with a brain tumor: an update.
AB  - Patients with brain tumors may suffer from cognitive deficits caused by the
      disease and/or its treatment. Here, we review recent efforts in the research on
      prevention or treatment of cognitive deficits in these patients. We conclude that
      interest in this area is growing, but that methodological difficulties persist.
      In addition, we describe the recently completed first randomized controlled trial
      on the effectiveness of cognitive rehabilitation that we conducted in patients
      with brain cancer. By reflecting on the methodological challenges experienced in
      our trial, we hope to assist others in planning and conducting future studies on
      both pharmacological treatments and cognitive rehabilitation programs for
      cognitive deficits in this patient population. We conclude with suggestions for
      future research directions.

PMID- 21080807
TI  - Peculiar features and tailored management of adult cancers occurring in pediatric
      age.
AB  - Most of the tumors typical of adult age, that is, gastrointestinal cancers,
      melanoma, lung and breast cancers, and carcinomas of the head and neck, may also
      occur - albeit very rarely - in children, and pediatric oncologists have defined
      them as 'rare (or very rare) pediatric tumors'. Given the scarce data available
      in the literature, the clinical management of children with these tumor types is
      a real challenge for pediatric oncologists and surgeons. Adult tumors often
      differ in many aspects from the malignancies typical of pediatric age, and the
      diagnostic and treatment guidelines adopted for children when they develop
      'adult' cancers are generally extrapolated from those applied to adults. However,
      the biology and clinical course of some adult tumors seem to change when they
      occur in children, thus suggesting the need for tailored approaches. This article
      describes a few such tumors and points to the need for forms of international
      cooperation with a view to gaining a better understanding of these particular
      conditions and improving patient management.

PMID- 21080805
TI  - Recent advances in the prevention and treatment of skin cancer using photodynamic
      therapy.
AB  - Photodynamic therapy (PDT) is a noninvasive procedure that involves a
      photosensitizing drug and its subsequent activation by light to produce reactive
      oxygen species that specifically destroy target cells. Recently, PDT has been
      widely used in treating non-melanoma skin malignancies, the most common cancer in
      the USA, with superior cosmetic outcomes compared with conventional therapies.
      The topical 'photosensitizers' commonly used are 5-aminolevulinic acid (ALA) and
      its esterified derivative methyl 5-aminolevulinate, which are precursors of the
      endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl
      5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion
      area of various skin diseases, which allows not only PDT treatment but also
      fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include
      various forms of non-melanoma skin cancer such as actinic keratosis, basal cell
      carcinoma and squamous cell carcinoma. The most recent and promising developments
      in PDT include the discovery of new photosensitizers, the exploitation of new
      drug delivery systems and the combination of other modalities, which will all
      contribute to increasing PDT therapeutic efficacy and improving outcome. This
      article summarizes the main principles of PDT and its current clinical use in the
      management of non-melanoma skin cancers, as well as recent developments and
      possible future research directions.

PMID- 21080810
TI  - Validation of a quality of life questionnaire in the Pacific Island.
AB  - PURPOSE: To adapt an existing validated quality of life instrument, the Impact of
      Vision Impairment (IVI) questionnaire for Pacific Island countries. METHODS:
      Following in-depth interviews (n = 24) and a pilot study (n = 67), the original
      32-item IVI questionnaire was translated and adapted in Vanuatu. The Melanesian
      IVI (IVI_M) was administered to participants not previously involved in the pilot
      study (n = 189). RESULTS: Participants included 117 (62%) with mild, moderate or
      severe vision impairment, 39 with unilateral loss and 33 with normal vision.
      Eighty-six percent of the original 32-items were deemed relevant by 90% of
      participants. Items displaying floor effects were removed (4), 2 were combined
      and 3 items rephrased to reflect Melanesian-specific activities, resulting in a
      23-item IVI_M. Nineteen items were relevant to both the Melanesian and Australian
      contexts including all 8 items related to the emotional reaction to vision loss.
      IVI_M demonstrated content and construct validity, reliability and discriminated
      visually healthy populations from those with vision impairment. Vision impairment
      of < 6/18 negatively effected quality of life. CONCLUSION: While the adaptation
      process demonstrated the need for culturally relevant instruments, it also
      highlighted the value of adapting existing validated instrument for use in cross
      cultural research rather than developing a new instrument from first principles.

PMID- 21080811
TI  - Direct-to-consumer genetic testing: driving choice?

PMID- 21080806
TI  - A new understanding in the epidemiology of melanoma.
AB  - The incidence of melanoma is continuing to increase worldwide. UV exposure is a
      known risk factor for melanoma. Geographic location is known to influence UV
      exposure and the distribution of the incidence of melanoma. Furthermore,
      epidemiologic data suggest that gender and genetics may influence the
      distribution of melanoma on the body surface and histopathologic characteristics
      of the lesion. This article describes what is known about the impact of gender,
      ethnicity and geography on the progression of melanoma. Advanced-stage cutaneous
      melanoma has a median survival time of less than 1 year. Surgical removal,
      radiotherapy, chemotherapy, targeted therapies and a variety of immunotherapies
      have been utilized in the treatment of melanoma. Current treatment strategies and
      the results of recent clinical trials are also discussed in this article.

PMID- 21080812
TI  - Telomere length as a risk marker for cardiovascular disease: the next big thing?

PMID- 21080813
TI  - Update on preimplantation genetic diagnosis for chromosomal abnormalities.

PMID- 21080815
TI  - Does additional hybridization also improve preimplantation genetic screening
      results?
AB  - EVALUATION OF: Mir P, Rodrigo L, Mateu E et al. Improving FISH diagnosis for
      preimplantation genetic aneuploidy screening. Hum. Reprod. 25(7), 1812-1817
      (2010). Mir et al. have evaluated the impact of additional hybridization rounds
      on FISH accuracy in preimplantation genetic screening (PGS) of aneuploidy. In a
      retrospective analysis of 1000 PGS cycles, embryo biopsy was performed on day 3.
      A greater number of embryos were diagnosed as chromosomally normal and were
      available for transfer after discarding 'false monosomies' and decreasing the
      number of noninformative embryos. The error rate for the FISH technique was 17.3%
      without and 5% with additional probes. A randomized controlled trial is needed to
      demonstrate improved clinical outcome. However, major obstacles in cleavage-stage
      PGS are chromosomal mosaicism and incomplete analysis. Therefore, polar body
      and/or trophectoderm analysis using 24 chromosome microarrays might be better
      alternatives.

PMID- 21080816
TI  - Approaches to understanding adaptations of skin color variation by detecting gene
      environment interactions.
AB  - Genetic and environmental factors are both part of an elaborate feedback
      mechanism whereby the human adaptive form reacts to environmental stimuli via
      internal adjustments. Human survival may ultimately depend on understanding two
      important components of future environmental adaptation. First, we must elucidate
      the dynamics of the human genome underpinning the complex human phenotype.
      Second, we must understand how the environment pressures and affects the genome,
      helping to determine human traits. This article reviews current approaches to
      detecting the natural selection of skin color variation in human populations. We
      include statistical methods for clarifying gene-environment interactions
      applicable to the interactions with UV radiation levels. We recommend spatial
      data mining as an efficient approach that applies environmental association
      rules, extending our knowledge of adaptation to the environment.

PMID- 21080817
TI  - Molecular diagnosis of acute myeloid leukemia.
AB  - The diagnosis and classification of acute myeloid leukemia is multifaceted,
      requiring the integration of a variety of laboratory findings, with genetic
      approaches now firmly established as a central component. Molecular genetic
      technologies continue to evolve and provide additional tiers of both clarity and
      complexity. Many have rapidly moved into clinical laboratories; others remain as
      relevant discovery tools, while some are poised to take their place in diagnostic
      testing menus. Here, we attempt to synthesize the role of various testing
      modalities and exciting nascent fundamental discoveries, with a view as to how
      these might be integrated into the contemporary and future evaluation of this
      group of aggressive hematologic malignancies.

PMID- 21080818
TI  - High-content affinity-based proteomics: unlocking protein biomarker discovery.
AB  - Single protein biomarkers measured with antibody-based affinity assays are the
      basis of molecular diagnostics in clinical practice today. There is great hope in
      discovering new protein biomarkers and combinations of protein biomarkers for
      advancing medicine through monitoring health, diagnosing disease, guiding
      treatment, and developing new therapeutics. The goal of high-content proteomics
      is to unlock protein biomarker discovery by measuring many (thousands) or all
      (~23,000) proteins in the human proteome in an unbiased, data-driven approach.
      High-content proteomics has proven technically difficult due to the diversity of
      proteins, the complexity of relevant biological samples, such as blood and
      tissue, and large concentration ranges (in the order of 10(12) in blood). Mass
      spectrometry and affinity methods based on antibodies have dominated approaches
      to high-content proteomics. For technical reasons, neither has achieved adequate
      simultaneous performance and high-content. Here we review antibody-based protein
      measurement, multiplexed antibody-based protein measurement, and limitations of
      antibodies for high-content proteomics due to their inherent cross-reactivity.
      Finally, we review a new affinity-based proteomic technology developed from the
      ground up to solve the problem of high content with high sensitivity and
      specificity. Based on a new generation of slow off-rate modified aptamers
      (SOMAmers), this technology is unlocking biomarker discovery.

PMID- 21080819
TI  - Molecular diagnosis of gestational trophoblastic disease.
AB  - Gestational trophoblastic disease consists of well-defined diagnostic entities of
      proliferative disorder of the placenta, of which hydatidiform moles are common
      lesions. Even with available ancillary studies, including ploidy and
      immunohistochemistry analyses, histological diagnosis of molar pregnancies can be
      challenging in a significant percentage of the cases. Reliable diagnostic
      approaches with improved sensitivity and specificity are highly desirable.
      Recently, PCR-based short tandem repeat DNA genotyping has emerged as a powerful
      diagnostic measure in the workup of gestational trophoblastic disorders,
      particularly hydatidiform moles.

PMID- 21080820
TI  - Exploiting the potential of molecular profiling in Parkinson's disease: current
      practice and future probabilities.
AB  - Parkinson's disease (PD) is a common, heterogeneous syndrome diagnosed clinically
      by the presence of classical neurological symptoms and the absence of 'red flags'
      that suggest alternative secondary parkinsonian disorders. Neuropathologically,
      nigrostriatal loss and the presence of proteinaceous inclusions (Lewy bodies)
      confirm the diagnosis. For PD, molecular profiling promises much but is yet to
      deliver in terms of breakthroughs for identifying at-risk individuals, detecting
      disease at early stages, improving diagnostic certainty, prognosticating future
      outcomes or providing surrogate markers of therapeutic efficacy. Recent, large
      scale omics studies, driven by technological advances, have generated terabytes
      of data but not yet met the goal of developing biomarkers suitable for clinical
      use in PD. In this article we critically evaluate the recent literature to
      identify the key roadblocks and realistic opportunities facing researchers
      interested in utilizing molecular profiling in the clinic to improve the
      diagnosis and treatment of PD.

PMID- 21080821
TI  - Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA
      and its inhibitor PAI-1.
AB  - The prognostic and/or predictive value of the cancer biomarkers, urokinase-type
      plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor
      [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for
      several cancer types in numerous clinically relevant retrospective or prospective
      studies, including a multicenter breast cancer therapy trial (Chemo-N0).
      Consequently, for the first time ever for any cancer biomarker for breast cancer,
      uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At
      present, two other breast cancer therapy trials, NNBC-3 and Plan B, also
      incorporating uPA and PAI-1 as treatment-assignment tools are in effect.
      Furthermore, small synthetic molecules targeting uPA are currently in Phase II
      clinical trials in patients afflicted with advanced cancer of the ovary, breast
      or pancreas.

PMID- 21080822
TI  - Ovarian cancer biomarkers for molecular biosensors and translational medicine.
AB  - Multiple omics researches in the past two decades have identified over 200
      potential biomarkers for ovarian cancer. Discoveries during the 1990s were more
      focused on clinicopathology-based biomarkers that were targeted to support
      diagnosis, but the emphasis has shifted to the identification of prognostic
      biomarkers in the past 10 years. The post-genomic era has opened the door for
      personalized cancer treatments and the trend of discovery is moving forward to
      identify more stratified biomarkers to accurately predict the progression of
      disease, as well as efficacy biomarkers to precisely determine drug response. To
      better meet future challenges, biomedical research needs the reformed and
      standardized infrastructure of tissue banks/biorepositories, with national and
      international initiatives. Of the hundreds of biomarker candidates for ovarian
      cancer, only a small number are actively being validated with clinical samples,
      owing to the lack of biomaterials that are linked with accurate clinical data.
      The purpose of this article is to present selected biomarkers from the past 20
      years of ovarian cancer research, placing special emphasis on biomarkers that are
      strongly associated with positive or negative clinical outcomes. The article also
      presents a global view of all known potential biomarkers and mutations for
      ovarian cancer from NCI's Cancer Gene Index developed by Sophic, and Sanger's
      Catalogue of Somatic Mutations in Cancer database.

PMID- 21080824
TI  - On the interaction of velar fronting and labial harmony.
AB  - This article documents the typological occurrence and interactions of two
      seemingly independent error patterns, namely Velar Fronting and Labial Harmony,
      in a cross-sectional investigation of the sound systems of 235 children with
      phonological delays (ages 3;0 to 7;9). The results revealed that the occurrence
      of Labial Harmony depends on the occurrence of Velar Fronting, and that, when
      these processes co-occurred, all three predicted types of interactions were
      attested. A constrained version of Optimality Theory is put forward that offers a
      unified explanation for the implicational relationship between these error
      patterns and their observed interactions. The findings are compared with the
      results from other studies and are considered for their theoretical and clinical
      implications.

PMID- 21080825
TI  - Characterising developmental language impairment in Serbian-speaking children: a
      preliminary investigation.
AB  - The aim of the article is to provide preliminary data on the use of auxiliaries
      and clitics in Serbian-speaking children with developmental language impairment.
      Two groups of children (a group of 30 children with developmental language
      impairment and a group of 30 typically developing children) aged between 48 and
      83 months and matched on IQ took part in the study. They were asked to tell a
      story from a series of four pictures. The results showed that the children with
      language impairment omitted significantly more auxiliary verbs and clitics than
      the controls. In addition, the rate of omission of auxiliaries and clitics did
      not decrease with increasing chronological age. We conclude that, as in other
      languages, auxiliary verbs and clitics are particularly difficult for Serbian
      speaking children with language impairment.

PMID- 21080826
TI  - Syntactic and lexical context of pauses and hesitations in the discourse of
      Alzheimer patients and healthy elderly subjects.
AB  - Psycholinguistic studies dealing with Alzheimer's disease (AD) commonly consider
      verbal aspects of language. In this article, we investigated both verbal and non
      verbal aspects of speech production in AD. We used pauses and hesitations as
      markers of planning difficulties and hypothesized that AD patients show different
      patterns in the process of discourse production. We compared the distribution,
      the duration and the frequency of speech dysfluencies in the spontaneous
      discourse of 20 AD patients with 20 age, gender and socio-economically matched
      healthy peers. We found that patients and controls differ along several lines:
      patients' discourse displays more frequent silent pauses, which occur more often
      outside syntactic boundaries and are followed by more frequent words. Overall
      patients show more lexical retrieval and planning difficulties, but where
      controls signal their planning difficulties using filled pauses, AD patients do
      not.

PMID- 21080827
TI  - Children with specific language impairment: The effect of argument-structure
      complexity on auditory sentence comprehension.
AB  - Children with specific language impairment (SLI) demonstrate consistent
      comprehension problems. The present study investigated whether these problems are
      driven primarily by structural complexity or length. A picture-sentence matching
      task was presented to 30 children: (1) 10 children with SLI, (2) 10 comprehension
      matched children with typical language development (TLD) and (3) 10 children with
      TLD matched for chronological age. Argument-structure complexity was manipulated
      independently of length, which was also independently varied. Results showed that
      argument-structure complexity had a greater influence on comprehension in
      children with SLI than in the comparison groups, with transitive sentences
      eliciting more errors than intransitive ones. This effect was not dependent on
      sentence length, which did not appear to affect the comprehension level. The
      results support the view that comprehension problems in children with SLI are
      principally related to the structural complexity of the sentence rather than the
      amount of material to be processed.

PMID- 21080828
TI  - The integrity of anticipatory coarticulation in fluent and non-fluent tokens of
      adults who stutter.
AB  - This article analysed the acoustic structure of voiced stop + vowel sequences in
      a group of persons who stutter (PWS). This phonetic unit was chosen because
      successful production is highly dependent on the differential tweaking of right
      to-left anticipatory coarticulation as a function of stop place. Thus, essential
      elements of both speech motor planning and execution can be parsimoniously
      assessed. Five adult PWS read three passages 3 times in a randomised order. These
      passages contained an overabundance of words beginning with initial [bV], [dV]
      and [gV] sequences. Digital audio and visual recordings were analysed to first
      identify fluent and stuttered target words, which were then spectrally analysed
      to yield locus equation (LE) regression plots. The slope of the LE regression
      function directly indexes the coarticulatory extent of the vowel's influence on
      the preceding stop consonant. The PWS revealed LE parameters falling within the
      normal ranges based on previously documented data obtained from fluent speakers.
      Theoretical considerations of possible underlying factors responsible for
      stuttering disfluencies are discussed relevant to these findings.

PMID- 21080829
TI  - Characteristics of phonological development as a risk factor for language
      development in Italian-speaking pre-term children: A longitudinal study.
AB  - This study analysed the early linguistic development of Italian pre-term
      children. Samples of spontaneous pre-linguistic and verbal production were
      recorded at 12 and 18 months of age from two groups of children: 24 pre-term
      children and 15 full-term children. The Italian version of the MacArthur-Bates
      Questionnaire was administered at 24 months of age. Comparisons between these two
      groups reveal differences in many aspects of phonetic and phonological
      development, such as consonantal inventory at 12 and 18 months of age and
      syllabic babbling complexity at 18 months of age. Results evidenced that birth
      weight was related with phonological skills exhibited at 18 months of age, and
      these skills in turn are related with vocabulary size at 24 months of age. Data
      are discussed within a theoretical framework that hypothesizes that early
      phonetic abilities have long-lasting effects on the process of language
      acquisition.

PMID- 21080832
TI  - AGE-RAGE in multiple sclerosis brain.
AB  - This pilot study used immunohistochemical techniques to investigate the advanced
      glycation end-product (AGE) Nepsilon-(carboxymethyl)lysine (CML) and its receptor
      (RAGE) in the brains of multiple sclerosis (MS) patients, comparing them with the
      brains of patients with Alzheimer's disease (AD) (positive controls) and with age
      matched control subjects (negative controls). Postmortem slides derived from the
      hippocampi of MS patients, AD patients, and controls were stained with monoclonal
      antibodies for CML and human RAGE. Results showed increased AGE and RAGE
      immunostaining in the hippocampi of MS patients, similar to AD patients.

PMID- 21080833
TI  - Amniotic membrane is an immunosuppressor of peripheral blood mononuclear cells.
AB  - Amniotic membrane (AM) is the inner layer of the placenta, which is in contact
      with the fetus; it has been used for transplantation in ocular surface diseases.
      It has been reported that amniotic membrane promotes epithelialization, inhibits
      angiogenesis and diminishes ocular inflammation. A persistent epithelial defect
      is the delay in epithelial wound healing caused by infiltrating inflammatory
      cells into the cornea and amniotic membrane transplantation has been successfully
      used in its treatment, however the mechanism of action in inhibiting inflammation
      it is not well understood. This study was aimed at determining whether denuded
      amniotic membrane (dAM) induces anti-inflammatory effects on peripheral blood
      mononuclear cells. METHODS: Human peripheral blood mononuclear cells (PBMC) were
      cultured on dAM. Proliferation and apoptosis assays were performed on PBMC; and
      synthesis and secretion of pro-inflammatory cytokines by these cells was
      analyzed. RESULTS: dAM induced apoptosis and inhibited cell proliferation of
      PBMC; and abolished the synthesis and the secretion of pro-inflammatory cytokines
      even when they were LPS stimulated. In contrast, when PBMC were cultured on
      hydrophilic membrane cell culture inserts, apoptosis was not significantly
      induced, cell proliferation was conserved, and synthesis and secretion of pro
      inflammatory cytokines were not affected. CONCLUSIONS: Taken together, these
      results could explain the anti-inflammatory in vivo effects observed when the
      amniotic membrane is used as a transplant.

PMID- 21080836
TI  - Connecting the circle from home to heart-failure disease management.

PMID- 21080835
TI  - Telemonitoring in patients with heart failure.
AB  - BACKGROUND: Small studies suggest that telemonitoring may improve heart-failure
      outcomes, but its effect in a large trial has not been established. METHODS: We
      randomly assigned 1653 patients who had recently been hospitalized for heart
      failure to undergo either telemonitoring (826 patients) or usual care (827
      patients). Telemonitoring was accomplished by means of a telephone-based
      interactive voice-response system that collected daily information about symptoms
      and weight that was reviewed by the patients' clinicians. The primary end point
      was readmission for any reason or death from any cause within 180 days after
      enrollment. Secondary end points included hospitalization for heart failure,
      number of days in the hospital, and number of hospitalizations. RESULTS: The
      median age of the patients was 61 years; 42.0% were female, and 39.0% were black.
      The telemonitoring group and the usual-care group did not differ significantly
      with respect to the primary end point, which occurred in 52.3% and 51.5% of
      patients, respectively (difference, 0.8 percentage points; 95% confidence
      interval [CI], -4.0 to 5.6; P=0.75 by the chi-square test). Readmission for any
      reason occurred in 49.3% of patients in the telemonitoring group and 47.4% of
      patients in the usual-care group (difference, 1.9 percentage points; 95% CI, -3.0
      to 6.7; P=0.45 by the chi-square test). Death occurred in 11.1% of the
      telemonitoring group and 11.4% of the usual care group (difference, -0.2
      percentage points; 95% CI, -3.3 to 2.8; P=0.88 by the chi-square test). There
      were no significant differences between the two groups with respect to the
      secondary end points or the time to the primary end point or its components. No
      adverse events were reported. CONCLUSIONS: Among patients recently hospitalized
      for heart failure, telemonitoring did not improve outcomes. The results indicate
      the importance of a thorough, independent evaluation of disease-management
      strategies before their adoption. (Funded by the National Heart, Lung, and Blood
      Institute; ClinicalTrials.gov number, NCT00303212.).

PMID- 21080839
TI  - Limits of medical research - some considerations.

PMID- 21080838
TI  - "Caring for people where they are": Addressing the double challenge of general
      practice at the 17th Nordic Congress of General Practice in Tromso 2011.

PMID- 21080841
TI  - Tamsulosin as adjunctive treatment after shockwave lithotripsy in patients with
      upper urinary tract stones: a systematic review and meta-analysis.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy of tamsulosin as an alpha(1)
      blocker in the treatment of the renal and ureteral stones after shockwave
      lithotripsy (SWL). MATERIAL AND METHODS: Relevant randomized controlled trials
      were identified by electronic and document searches of MEDLINE, EMBASE, the
      Chinese Biomedical Disk and the Cochrane Central Register of Controlled Trials
      until April 2010. No language restriction was applied. Trials were included if
      patients were randomized to receive either tamsulosin or standard therapy with or
      without placebo after SWL. The main outcome was the stone clearance rate. Two
      reviewers independently assessed trial quality and extracted data. Meta-analysis
      was conducted with Review Manager (RevMan) version 5.0. RESULTS: Fifteen studies
      involving 1326 subjects met the inclusion criteria. Study duration ranged from 2
      weeks to 3 months. The pooled analysis showed a 24% [risk ratio (RR) = 1.24, 95%
      confidence interval (CI) 1.12 to 1.37] improvement in stone clearance tamsulosin.
      According to stone locations (renal, upper ureteral and lower ureteral), the
      pooling effects of tamsulosin were analysed, with a higher expulsion rate
      obtained than control (RR = 1.38, 1.83, 1.43, and 95% CI 1.17 to 1.61, 1.20 to
      2.78, 1.13 to 1.81, respectively). Tamsulosin 0.4 mg had a high possibility of
      achieving successful outcome (RR = 1.29, 95% CI 1.14 to 1.47). In addition, a
      shorter expulsion time, lower analgesic requirements, fewer colic episodes and
      adverse effects were observed. CONCLUSIONS: Tamsulosin is a safe and effective
      therapy for renal and ureteral stones after SWL. Further, high-quality randomized
      trials are necessary to confirm its efficacy.

PMID- 21080843
TI  - Heritability and environmental effects for self-reported periods with stuttering:
      a twin study from Denmark.
AB  - Genetic influence for stuttering was studied based on adult self-reporting. Using
      nation-wide questionnaire answers from 33,317 Danish twins, a univariate
      biometric analysis based on the liability threshold model was performed in order
      to estimate the heritability of stuttering. The self-reported incidences for
      stuttering were from less than 4% for females to near 9% for males. Both
      probandwise concordance rate and tetrachoric correlation were substantially
      higher for monozygotic compared to dizygotic pairs, indicating substantial
      genetic influence on individual liability. Univariate biometric analyses showed
      that additive genetic and unique environmental factors best explained the
      observed concordance patterns. Heritability estimates for males/females were
      0.84/0.81. Moderate unique environmental effects were also found.

PMID- 21080844
TI  - Cell treatment after acute myocardial infarction prevents early decline in
      circulating IGF-1.
AB  - OBJECTIVES: To examine the influence of intracoronary autologous bone marrow cell
      transplantation after acute myocardial infarction on circulating growth factors
      and their relationship to left ventricular function. METHODS: Circulating insulin
      like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), stromal derived
      factor-1-alpha (SDF-1alpha), and transforming growth factor beta (TGF-beta) were
      measured in patients randomized to cell treatment or control, in the ASTAMI
      study. Autologous cells were injected intracoronary on day 6; blood was sampled
      on days 5, 9, and at three months. Left ventricular ejection fraction was
      recorded by electrocardiogram-gated single photon emission computed tomography at
      six months. RESULTS: Only change in IGF-1 from baseline to three months differed
      between groups (p = 0.024). A weak but significant correlation was found between
      left ventricular ejection fraction and the averaged IGF-1 concentrations of all
      patients (r = 0.24, p = 0.02). Patients with IGF-1 above or below median (102
      ng/ml) had a left ventricular ejection fraction of 52.3% (+/-11.4) versus 46.4%
      (+/-12.2) respectively (p = 0.017). CONCLUSIONS: Intracoronary bone marrow cell
      treatment after myocardial infarction attenuates a reduction in circulating IGF
      1. IGF-1 levels over time were weakly, but significantly correlated to left
      ventricular ejection fraction.

PMID- 21080845
TI  - Metoprolol, but not atenolol, reduces stress induced neuropeptide Y release in
      pigs.
AB  - OBJECTIVES: To explore if beta-adrenergic receptors in the brain are involved in
      acute and delayed cardiovascular responses to a brief emotional stress, by
      comparing the effects of the beta1-blockers metoprolol (lipophilic) and atenolol
      (hydrophilic). DESIGN: Male dominant pigs, singleliving, freely moving, with
      telemetric recordings of intra-arterial pressure and ECG and assay of plasma
      levels of the adrenergic cotransmitter neuropeptide Y (NPY), were confronted with
      four alien pigs for three minutes at weekly intervals. Weeks 1 and 4 were
      controls, in weeks 2 and 3 randomized crossover treatment with metoprolol or
      atenolol were given. RESULTS: The confrontation caused instant and transient
      tachycardia and more prolonged effects in terms of increased plasma NPY levels,
      increased arterial pressure and reduced cardiac vagal activation. The two beta
      blockers inhibited the tachycardia equally, but only metoprolol reduced the
      prolonged effects. CONCLUSIONS: Emotionally induced sympathetic activation
      involves peripheral release of NPY causing a prolonged increase of arterial
      pressure and a reduction of cardiac vagal activity. These effects are prevented
      by central nervous beta-adrenoceptor blockade.

PMID- 21080846
TI  - Depression predicts perioperative outcomes following coronary artery bypass graft
      surgery.
AB  - OBJECTIVES: To assess preoperative depression in middle-aged men undergoing
      coronary artery bypass graft surgery (CABG) and to determine if depression is
      related to perioperative outcomes. DESIGN: One hundred and nine middle-aged male
      patients were randomly selected and assessed for depression one day before CABG
      using the Symptom Checklist-90 Revised (SCL-90R). Perioperative outcomes were:
      (1) postoperative length of hospital stay, (2) the presence of any early
      complications (at intensive care unit), and (3) the presence of any late
      complications (at cardiac surgery unit). RESULTS: Twenty-five (23%) patients had
      a high level of depression. Preoperative depression scores significantly
      predicted postoperative length of hospital stay (p < 0.001) and the incidence of
      late perioperative complications (p < 0.05) independently from biomedical and
      sociodemographic factors. Each increase in depression T score increased the odds
      of occurrence of late complications by 10% (p = 0.018, CI 95% 1.02-1.19).
      CONCLUSIONS: Depression is common in middle-aged men undergoing CABG and is an
      independent predictor of postoperative length of hospital stay and late
      perioperative complications.

PMID- 21080847
TI  - Patterns of smoking behaviour in patients following cardiac surgery. A
      prospective study.
AB  - OBJECTIVES: To describe patterns of smoking behaviour in patients undergoing
      cardiac surgery. DESIGN: A prospective population-based study of patients
      undergoing cardiac surgery between September 2004 and September 2005. Smoking
      behaviour and socio-demographic variables were obtained by questionnaires at
      baseline, six and 12 months after surgery. RESULTS: At baseline 534 patients
      (median age 69 years, 23% females) were included, 89% responded after six and 12
      months. At baseline 14% (n = 74) were current smokers, 59% (n = 316) were former
      smokers and 27% (n = 143) had never smoked. At six months 8% were current smokers
      (n = 36) while 9% (n = 40) were current smokers at 12 months. A total of nine
      smokers had relapsed at 12 months. CONCLUSION: About half of the current smokers
      gave up smoking after cardiac surgery. Changes in smoking behaviour were most
      likely to occur during the first six months. This supports that smoking cessation
      interventions should continue after discharge. Cardiac surgery can serve as a
      teachable moment; an opportunity to encourage patients to give up smoking and
      prevent relapses among those who stopped smoking before surgery.

PMID- 21080848
TI  - Initial experience with the Freedom Solo(r) stentless aortic valve in a low
      volume centre.
AB  - OBJECTIVES: Freedom Solo is a stentless biological aortic valve which is
      implanted supra-annularly with a single suture line. An increased risk of
      postoperative thrombocytopenia in the early postoperative period has been
      reported in recent studies. In our study we evaluated postoperative haemodynamic
      performance and thrombocyte-levels. DESIGN: Thirty seven patients who underwent
      valve implantation of the Sorin Freedom Solo stentless valve were included. The
      haemodynamic performance of the valve was evaluated by transthoracic
      echocardiography postoperatively at the fourth day (mean) and after a median of
      4.2 months. RESULTS: The mean gradient (mmHg) of Freedom Solo was 7.5 at four
      days and 8.6 at 4.2 months. Postoperatively no patient had more than grade 1
      leakage. Seven percent of the patients had a reduction of thrombocytes to less
      than 20% of the preoperative level. Seventy six percent had a minimum
      postoperative thrombocyte level less than 100*10(9)/L. The 30 days mortality in
      our patient material was zero. CONCLUSIONS: Implantation of the Freedom Solo
      valve was uncomplicated in our experience. Favourable transvalvular gradients and
      no significant leaks were found. In accordance with the literature, we found a
      high percentage of patients having a postoperative level of thrombocytes less
      than 100*10(9)/L after implantation of Freedom Solo.

PMID- 21080849
TI  - Hazards with electrocautery-induced decomposition of fatty acids--in view of
      lipid embolization.
AB  - OBJECTIVES: Electrocautery is an appreciated surgical tool, which however,
      generates immense heat and fat-tissue melting. In cardiac surgery, liquefied fat
      collects on the surface of blood in the pericardial cavity and becomes aspirated
      by the heart-lung machine for aortic recycling. Deposits seen in the brain
      microcirculation after surgery are caused by lipid embolism. This study
      investigates lipid chemistry, whether heat from electrocautery generates fatty
      acid fragmentation and decomposition. DESIGN: Pericardial fat tissue was sampled
      from cardiac-surgery patients and from piglets. The human tissue was exposed to
      electrocautery, or to fixed temperatures in an in vitro model. Fatty-acid
      decomposition was explored by solid-phase microextraction gas chromatography and
      the distribution of fatty acids was measured. RESULTS: Fatty-acid decomposition
      demonstrated a temperature-effect relationship (p = 0.007). At 350 degrees C the
      proportion of polyunsaturated fatty acids became heavily reduced or were
      abolished (p = 0.016). Electrocautery resulted in similar changes. CONCLUSIONS:
      Electrocautery induces a profound fatty-acid fragmentation to form short-chained
      compounds. The chemical and toxic nature of these compounds remains to be
      determined, including their clinical implications at blood recycling in cardiac
      surgery.

PMID- 21080852
TI  - Successful clozapine rechallenge after acute myocarditis.

PMID- 21080850
TI  - Reference spectra from squamous epithelium and connective tissue allow whole
      section proteomics analysis.
AB  - We reasoned that micro-dissection of tumour cells for protein expression studies
      should be omitted since tumour-stroma interactions are an important part of the
      biology of solid tumours. To study such interactions in head and neck squamous
      cell carcinoma (HNSCC) development, we generated reference protein spectra for
      normal squamous epithelium and connective tissue by SELDI-TOF-MS. Calgranulins A
      and B, Annexin1 and Histone H4 were found to be strongly enriched in the
      epithelium. The alpha-defensins 1-3 and the haemoglobin subunits were identified
      in the connective tissue. Tumour-distant epithelia, representing early pre
      malignant lesions, showed up-regulated expression of the stromal alpha-defensins,
      whereas the epithelial Annexin 1 was down-regulated. Thus, tumour
      microenvironment interactions occur very early in the carcinogenic process. These
      data demonstrate that omitting micro-dissection is actually beneficial for
      studying changes in protein expression during development and progression of
      solid tumours.

PMID- 21080851
TI  - Psychological distress is associated with tobacco smoking and quitting behaviour
      in the Australian population: evidence from national cross-sectional surveys.
AB  - OBJECTIVE: To investigate the association between levels of psychological
      distress and smoking and quitting behaviours. METHOD: Data were from two large
      Australian national household surveys of individuals over 20 years of age. Level
      of psychological distress was measured by the Kessler 10 scale. Tobacco smoking
      measures included current smoking status (never, former, current); ex-smokers'
      time since quitting; current smokers' abstinent period in the last 12 months,
      cigarettes smoked per day, reasons for smoking, and self-report of factors that
      would motivate quitting; and self-report of factors that motivated smokers to
      quit in the last 12 months. Multinomial logistic regression was used to assess
      the relationships between smoking behaviours and psychological distress, while
      controlling for socio-demographic factors. RESULTS: Current smokers, especially
      those who smoke more cigarettes per day and those who report less success at
      quitting or reducing smoking, had higher levels of psychological distress. Ex
      smokers were also more likely to experience psychological distress than those who
      never smoked, but the association weakened with more years since quitting.
      Current smokers with psychological distress were just as, or more likely, to
      report planning to quit as those without psychological distress. Smokers who did
      not plan to quit due to addiction, past failure at quitting, and using smoking
      for relaxation or to deal with stress were more likely to report psychological
      distress than those who did not report these reasons. CONCLUSIONS: Current
      smoking and unsuccessful quit attempts in the Australian community were strongly
      associated with symptoms of psychological distress. Quitting aspirations and
      influence from general public health interventions were not associated with the
      smokers' level of psychological distress.

PMID- 21080853
TI  - Probiotic strategies for the treatment and prevention of bacterial vaginosis.
AB  - IMPORTANCE OF THE FIELD: Urogenital infections are on average the number-one
      reason for women to visit the doctor. Yet, treatment and preventive strategies
      have gone unchanged for close to 50 years. With prevalence rates for bacterial
      vaginosis at more than 29%, depending on the population, and similarly high
      incidences of vulvo-vaginal candidiasis and urinary tract infections, plus HIV,
      new therapies are urgently needed to improve the health of women around the
      world. AREAS COVERED IN THE REVIEW: This review discusses the vaginal microbiota,
      our improved understanding of its composition, and its role in health and
      disease. It also discusses the progress made in the past 10 years or so, with the
      development and testing of probiotic lactobacilli to improve vaginal health and
      better manage urogenital infection recurrences. WHAT THE READER WILL GAIN: The
      reader will have an understanding of the clinical data obtained so far, and the
      potential mechanisms of action of probiotics. Despite the need for more clinical
      studies, the review illustrates a case for inclusion of probiotics as part of the
      approach to disease prevention, and as an adjunct to antimicrobial treatment.
      Challenges remain in optimizing clinical benefits, selecting new strains,
      preparing new products and having them tested in humans then approved with
      informative claims, and making products readily accessible to women in the
      developed and developing world. TAKE HOME MESSAGE: The vaginal microbiota is a
      complex structure that can change quickly and dramatically, and significantly
      impact a woman's health. New health-maintenance and disease-treatment approaches
      are badly needed, and probiotics should be considered.

PMID- 21080854
TI  - Sertindole for the treatment of schizophrenia.
AB  - IMPORTANCE OF THE FIELD: Despite considerable progress in the pharmacological
      treatment of schizophrenia, unmet needs remain concerning refractory patients, as
      well as improvement of negative symptoms, cognition, quality of life, adherence
      and tolerability. Sertindole, a second-generation antipsychotic with high
      affinity for dopamine D2, serotonin 5-HT2(A), 5-HT2(C), and alpha1-adrenergic
      receptors, is the first phenylindole-derived antipsychotic agent. AREAS COVERED
      IN THIS REVIEW: Pharmacodynamics, pharmacokinetics, clinical efficacy, safety and
      cost-effectiveness of sertindole are covered based on a literature review
      (PubMed) from 1990 to 2010. Pivotal as well as supportive randomized controlled
      trials are reviewed along with observational and/or naturalistic safety studies.
      WHAT THE READER WILL GAIN: This review of sertindole will allow the reader to
      determine the place for sertindole in the schizophrenia treatment landscape. TAKE
      HOME MESSAGE: Studies conducted so far suggest a beneficial effect of sertindole
      on positive and negative symptoms as well as on cognition, relapse prevention and
      quality of life. There is also some evidence for the treatment of refractory
      patients. Sertindole induces moderate weight gain, with few extrapyramidal
      symptoms and metabolic changes. More head-to-head comparisons with other second
      generation antipsychotics are, however, still needed as well as further
      clarification on cardiac safety.

PMID- 21080855
TI  - Emerging role of the histone deacetylase inhibitor romidepsin in hematologic
      malignancies.
AB  - IMPORTANCE OF THE FIELD: Histone acetylation plays a crucial role in chromatin
      modification and the regulation of gene expression. Histone deacetylase
      inhibitors (HDACi) are a novel class of antitumor agents with pleiotropic
      effects; they are under active clinical investigation. The HDACi romidepsin is
      being evaluated in a variety of tumors and was recently approved for the
      treatment of cutaneous T-cell lymphomas (CTCL). AREAS COVERED IN THIS REVIEW:
      This review focuses on the findings from early Phase trials involving romidepsin,
      and the Phase II trial results that led to the approval of romidepsin in CTCL.
      WHAT THE READER WILL GAIN: Mechanisms of action of HDACi, including romidepsin,
      are described in this review and the pharmacodynamic and pharmacokinetic
      properties of romidepsin are summarized. The efficacy and safety profile of
      romidepsin in clinical trials in T-cell lymphoma is reviewed, and emerging data
      on single-agent and combination strategies in myeloid and B-lymphoid malignancies
      is outlined. TAKE HOME MESSAGE: Romidepsin has significant activity and an
      acceptable safety profile in CTCL and peripheral T-cell lymphomas. Its use in
      rationally designed combination approaches is under active investigation in B
      lymphoid malignancies.

PMID- 21080856
TI  - Where is dihydroergotamine mesylate in the changing landscape of migraine
      therapy?
AB  - IMPORTANCE OF THE FIELD: Migraine affects approximately 18% of women and 6% of
      men, and has an immense impact on quality of life and productivity. Advancement
      in therapeutic options has been slow. For many patients with difficult-to-treat
      migraine, the appropriate use of dihydroergotamine mesylate (DHE) can result in
      treatment success and unprecedented patient satisfaction. AREAS COVERED IN THIS
      REVIEW: Migraine treatment guidelines regarding the role of DHE are highlighted.
      An overview of the market for antimigraine drugs is provided in the context of
      DHE, since its introduction in 1943, and the novel agents that are likely to be
      available in the near future. An extensive literature search was undertaken using
      Medline and the Cochrane Systematic Review and Clinical Trial databases. WHAT THE
      READER WILL GAIN: An understanding of which migraine patients are likely to
      benefit maximally from treatment with DHE in its various forms. TAKE HOME
      MESSAGE: In the most difficult patient groups - including those with status
      migrainosus, migraine recurrence, medication-overuse headache, and chronic daily
      headache - DHE has therapeutic efficacy superior to other agents. The side-effect
      profile of DHE is more benign than is often perceived and should not be a
      deterrent for use in well-chosen cases.

PMID- 21080857
TI  - The therapeutic potential of engineered human neovessels for cell-based gene
      therapy.
AB  - IMPORTANCE OF THE FIELD: Several works have shown the feasibility of engineering
      functional blood vessels in vivo using human endothelial cells and mural cells.
      In this context, the genetic modification of endothelial cells would ensure the
      secretion of a therapeutic protein into the systemic circulation for a prolonged
      period of time. AREAS COVERED IN THIS REVIEW: We discuss the different strategies
      aimed at the formation of long-lasting neovessels in vivo, using human
      endothelial and mural cells. The main focus is the potential of these constructs
      in gene therapy strategies for the in vivo production of therapeutic proteins.
      WHAT THE READER WILL GAIN: The reader will have an outline of the different types
      of cells that have been used for microvessel engineering in vivo, as well as
      scaffolds employed to seed these cells. We provide a critical review of their
      advantages and drawbacks, along with examples of their potential in cell-based
      gene therapy strategies. TAKE HOME MESSAGE: There is a real potential for
      neovessels derived from human endothelial and mural cells to be incorporated in
      clinical interventions, either as a cell-based gene therapy to produce a
      therapeutic protein or as a component of engineered tissue constructs in
      regenerative medicine.

PMID- 21080858
TI  - Immunotherapy for metastatic prostate cancer: where are we at with sipuleucel-T?
AB  - IMPORTANCE OF THE FIELD: Prostate cancer is the leading malignancy in North
      American men and despite improvements in treatments 20 - 30% of patients will
      relapse. Immunotherapy using activated mononuclear cells is a way to harness the
      body's adaptive immune response to fight metastatic prostate cancer. AREAS
      COVERED IN THIS REVIEW: In 2005, at least 10 therapeutic cancer vaccines,
      designed to confer active, specific immunotherapy against tumor-associated
      antigens, were in clinical trials. These covered potential fields of
      immunological strategy to overcome castration-resistant prostate cancer. WHAT THE
      READER WILL GAIN: A literature review was performed using the search terms
      sipuleucel-T, Provenge and APC8015 or APC-8015, and restricted to English
      language articles from 2000 to 2010. The immunological design and development of
      sipuleucel-T are summarized. The efficacy and safety of sipuleucel-T are
      discussed based on current data from clinical trials. Ongoing clinical trials
      involving sipuleucel-T are summarized. TAKE HOME MESSAGE: Efficacy and safety
      with sipuleucel-T has been demonstrated in Phase I/II trials. The latest data
      from a Phase III trial shows that sipuleucel-T has met the primary endpoint of
      survival benefit. Further work is needed to understand the mechanisms behind
      cancer vaccine failure and elucidate the population for whom this vaccine will be
      suitable.

PMID- 21080859
TI  - Single-use disposable dry powder inhalers for pulmonary drug delivery.
AB  - IMPORTANCE OF THE FIELD: The understanding of pulmonary drug delivery and thus
      its utilization for medical purposes has remarkably advanced over the last
      decades. It has been recognized that this route of administration offers many
      advantages and several drug delivery systems have been developed accordingly.
      Thereby, single-use disposable dry powder inhalers may be considered an
      economically and therapeutically valuable option for both local and systemic
      administration of drugs to treat a variety of different disease states. AREAS
      COVERED IN THIS REVIEW/WHAT THE READER WILL GAIN: This review highlights the
      required characteristics and potential applications of single-use disposable dry
      powder inhalers considering advantages as well as limitations of these drug
      delivery devices. Until now, such drug delivery systems have not become widely
      accepted. Several devices are available or under development and a few products
      have reached or completed the clinical phase, but none of them have received
      market authorization as yet. TAKE HOME MESSAGE: Recent advances in formulation
      and device design, however, can be considered encouraging and should eventually
      lead to a wider establishment of single-use disposable dry powder inhalers in
      pulmonary drug delivery.

PMID- 21080860
TI  - Drug delivery using multifunctional dendrimers and hyperbranched polymers.
AB  - IMPORTANCE OF THE FIELD: The review presents the design strategy and synthesis of
      multifunctional dendrimers and hyperbranched polymers with the objective to
      develop effective drug delivery systems. AREAS COVERED IN THIS REVIEW: Well
      characterized, commercially available dendritic polymers were subjected to
      functionalization for preparing drug delivery systems of low toxicity, high
      loading capacity, ability to target specific cells and transport through their
      membranes. This has been achieved by surface targeting ligands, which render the
      carriers specific to certain cells and polyethylene glycol groups, securing water
      solubility, stability and prolonged circulation. Moreover, transport agents
      facilitate transport through cell membranes while fluorescent probes detect their
      intracellular localization. A common feature of surface groups is multivalency,
      which considerably enhances their binding strength with complementary cell
      receptors. To these properties, one should also add the property of attaining
      high loading of active ingredients coupled with controlled and/or triggered
      release. WHAT THE READER WILL GAIN: Readers will be exposed to the strategy of
      synthesizing multifunctional polymers, aimed at the development of effective drug
      delivery systems. TAKE HOME MESSAGE: Multifunctional systems upgrade the
      therapeutic potential of drugs and, in certain cases, may even lead to the
      application of new bioactive compounds that would otherwise not be feasible.

PMID- 21080861
TI  - ATLAS trials: efficacy and safety of telavancin compared with vancomycin for the
      treatment of skin infections.
AB  - Telavancin is an injectable lipoglycopeptide that is bactericidal in vitro
      against staphylococci, streptococci and vancomycin-susceptible enterococci.
      Telavancin inhibits bacterial cell wall synthesis by interfering with the
      synthesis of peptidoglycan, and binds to the bacterial membrane and disrupts
      membrane barrier function. The Assessment of Telavancin in cSSSI (ATLAS) program,
      comprising of two Phase III clinical trials, demonstrated noninferiority of
      telavancin to vancomycin for the treatment of complicated skin and skin-structure
      infections including infections due to methicillin-resistant Staphylococcus
      aureus (MRSA). Among clinically evaluable patients with MRSA isolated at baseline
      in the pooled study population, the clinical cure rate was 87.0% (208 out of 239)
      for patients treated with telavancin and 85.9% (225 out of 262) for patients
      treated with vancomycin. The most common telavancin treatment-emergent adverse
      events were taste disturbance, nausea, vomiting and foamy urine. Renal adverse
      events occurred in 3% of telavancin-treated patients and 1% of vancomycin-treated
      patients. Telavancin is now approved in the USA and Canada for the treatment of
      Gram-positive complicated skin and skin-structure infections.

PMID- 21080862
TI  - Medical publication under fire.

PMID- 21080863
TI  - Change in blood pressure during hospitalisation for acute heart failure predicts
      mortality.
AB  - OBJECTIVE: In patients with acute heart failure (HF) there is an inverse relation
      between blood pressure (BP) and mortality but the prognostic impact of the change
      in BP between admission and discharge is not known. The primary objective was to
      study the impact of the change in BP during a hospitalisation for acute HF on
      prognosis. DESIGN: We studied 208 consecutive patients admitted with acute heart
      failure and discharged alive, age 77 +/- 10 years, 49.5% women. RESULTS: BP at
      admission was 145 +/- 35/85 +/- 9 mmHg compared to 132 +/- 24/76 +/- 13 mmHg at
      discharge. The average number of BP lowering medications at admission and
      discharge was 2.1 +/- 1.2 and 2.8 +/- 1.0 respectively. The average number of BP
      lowering medications with dose increased at discharge compared to admission was
      0.3 +/- 0.5. Univariate predictors of all-cause mortality at 12 and/or 40 months
      were admission SBP and DBP, discharge DBP, decrease in SBP and DBP during
      hospitalisation, age, eGFR, number of added BP-lowering medications during the
      hospitalisation and left ventricular ejection fraction (LVEF). Multivariate
      predictors at 12 and/or 40 month were admission DBP, decrease in DBP, age, eGFR,
      LVEF and number of new BP-lowering medications added during the hospitalisation.
      CONCLUSIONS: A decrease in BP during hospitalisation for acute heart failure was
      a predictor of all cause mortality. A higher admission BP and the tolerability of
      added medications probably played a role, and our findings need confirmation in
      larger studies.

PMID- 21080864
TI  - Assessment of response criteria to cardiac resynchronization therapy (CRT) and
      prediction of response.
AB  - AIMS: Approximately 30% of patients treated with cardiac resynchronization
      therapy (CRT) do not respond. We evaluated response to CRT at six and 12 months,
      tested a novel response criterion and evaluated different clinical and
      echocardiographic predictors of response. METHODS AND RESULTS: Eighty one
      patients were enrolled. A definition of response to CRT was predefined as a
      combination of 1) a reduction of LV end-systolic volume of >=10% and 2) either an
      improvement in NYHA class by >=1 or an increase in peak oxygen consumption of >=1
      ml/kg/min. Pre-and postoperatively at six and 12 months we also evaluated the
      most commonly employed definitions of response in our material: NYHA class,
      quality of life, left ventricular (LV) performance and functional capacity. After
      six and 12 months of CRT, 42 (52%) and 48 patients (59%) were responders,
      respectively. Employing different criteria, response ranged from 33-96% and 31
      94% at six and 12 months, respectively. In our material a large pre-operative
      interventricular motion delay (IVMD) was a predictor of response to CRT (p<0.05).
      CONCLUSIONS: Fifty two percent and 59% were responders to CRT at six months and
      one year given a predefined novel endpoint. Different response criteria to CRT
      gave response rates ranging from 33-96% and 31-94% at six and 12 months,
      respectively. A large IVMD predicts response to CRT at six and 12 months.

PMID- 21080865
TI  - Simvastatin prevents ERK activation in myocardial hypertrophy of spontaneously
      hypertensive rats.
AB  - BACKGROUND: Statins exert regression of left ventricular hypertrophy independent
      of their plasma cholesterol-lowering actions. However, the underlying mechanism
      is not clear. METHODS: We tested the hypothesis that the extracellular signal
      regulated kinases (ERKs) signaling pathway could be a target of simvastatin (SIM)
      and involved in SIM-induced LVH regression in spontaneously hypertensive rats
      (SHR). Fourteen 14-week old-SHR males were randomly divided into a SHR SIM group
      (n = 7) or a SHR control group (n = 7). The SHR SIM group was given SIM 40 mg/kg
      . d via injection ig, while the SHR control group was routinely given only
      vehicle (0.5% carboxymethyl cellulose ig). Seven Wistar Kyoto rats served as
      normal controls. RESULTS: Ten weeks of treatment with SIM in SHR had no influence
      on blood pressure. The ratio of left ventricle weight to body weight in the SHR
      SIM group was decreased significantly compared to that in the SHR control group
      (p < 0.05). Among the three groups there was no significant difference in total
      ERK expression (p > 0.05). SIM treatment caused a significant reduction in the
      expression of phosphorylated-ERK, the kinase activity of ERK, the levels of
      mitogen-activated protein kinase phosphatase-1 protein and its mRNA (p <0.01 for
      all). CONCLUSIONS: The Hydroxymethylglutaryl coenzyme A reductase inhibitor SIM
      prevents the activation of ERK in SHR to mediate regression of myocardial
      hypertrophy in SHR.

PMID- 21080866
TI  - Heart transplantation with ABO-identical versus ABO-compatible cardiac grafts:
      influence on long-term survival.
AB  - OBJECTIVES: To compare identical versus compatible, ABO blood group matching
      effects on rejection and long-term survival after heart transplantation (HT).
      DESIGN: Data were collected from 196 patients who underwent HT at Lund University
      Hospital between 1988 and 2008. Cox proportion hazard regression analysis was
      used to identify factors associated with reduced long-term survival. RESULTS: One
      hundred and sixty six patients (85%) had an identical ABO blood group match and
      30 patients (15%) had a compatible, ABO blood group match. Four non
      pharmacological variables reducing overall survival were identified: recipient
      blood group AB, age >55 years, ischemic time, and year of transplantation. Two
      pharmacological variables improved overall survival: glucocorticoids and
      cyclosporine. There was no significant difference in long-term survival between
      patients with identical blood groups compared to compatible ABO blood group
      matching. However, there was a trend towards graft failure as cause of death
      being more common in the compatible ABO group match compared identical blood
      group match (13% versus 5%, p=0.118). CONCLUSIONS: Six factors associated with
      overall survival were identified. One of these was related to blood group AB. No
      significant difference in survival following identical, versus compatible, ABO
      matching was demonstrated.

PMID- 21080867
TI  - Blood concentrations are better predictors of chioroquine poisoning severity than
      plasma concentrations: a prospective study with modeling of the
      concentration/effect relationships.
AB  - INTRODUCTION: Chloroquine causes rare but life-threatening toxicity. The
      prognostic value of plasma chloroquine concentrations in acute poisonings remains
      poorly investigated. We investigated the hypothesis that blood chloroquine
      concentrations better predicted chloroquine poisoning severity than plasma
      concentrations. METHODS: A prospective study of consecutive chloroquine
      poisonings admitted to an intensive care unit from 2003 to 2007 was performed
      with simultaneous measurements of blood and plasma chloroquine (chloroquine and
      desethylchloroquine) concentrations. A population pharmacokinetic-pharmacodynamic
      model described epinephrine infusion rate, our surrogate marker of cardiovascular
      toxicity, as function of blood or plasma chloroquine concentrations. RESULTS:
      Forty-four patients [29F/15M, 33 years (25-41), median (25-75th percentile), 34%
      with cardiac arrest] were included. Management included mechanical ventilation
      (80%), 8.4% sodium bicarbonate (66%), epinephrine [73%, maximal rate: 2.8 mg/h
      (0.8-5.0)], and extracorporeal life support (16%). Seven patients died. Blood
      [6.7 mg/L (4.0-13.0)] and plasma [1.5 mg/L (1.2-2.9)] chloroquine concentrations
      were weakly, although significantly correlated (r = 0.66, p < 0.0001, Spearman
      test). Admission chloroquine concentrations correlated with the reported ingested
      dose (r = 0.70 for blood vs. 0.48 for plasma), QRS duration (r = 0.82 vs. 0.64),
      lactate concentrations (r = 0.63 vs. 0.47), and epinephrine infusion rates (r =
      0.70 vs. 0.62). Chloroquine concentrations differed significantly between
      patients with and without cardiac arrest (p = 0.0002 for blood vs. 0.02 for
      plasma). A one-compartment pharmacokinetic (PK) model adequately described blood
      chloroquine concentrations. An effect compartment linked to the blood compartment
      adequately described plasma chloroquine concentrations. Using a sigmoidal E(max)
      pharmacodynamic (PD) model, epinephrine infusion rate was better predicted with
      blood than plasma concentrations (p < 0.01), suggesting that time-course of blood
      concentrations is a better prognostic value than plasma concentrations.
      CONCLUSION: Immediate and serial measurements of blood chloroquine concentrations
      are better than plasma for predicting cardiovascular severity of chloroquine
      poisonings.

PMID- 21080868
TI  - Current concepts in the pathology and epigenetics of endometrial carcinoma.
AB  - In the Western world, endometrial carcinoma is the most common malignant tumour
      of the female genital tract and is the fourth most common cancer in women. Two
      different clinicopathological subtypes are recognised: the oestrogen-related
      (type I, endometrioid) and the non-oestrogen related (type II, non-endometrioid).
      This article reviews the epidemiology, risk factors, genetic alterations during
      endometrial carcinogenesis, features of tumours and precursors and early
      detection of the disease. Insights into the epigenetic alterations, with emphasis
      on DNA methylation during endometrial carcinogenesis, and their diagnostic value
      are also provided.

PMID- 21080869
TI  - Evidence-based pathology: umbilical cord coiling.
AB  - The generation of a pathology test result must be based on criteria that are
      proven to be acceptably reproducible and clinically relevant to be evidence
      based. This review de-constructs the umbilical cord coiling index to illustrate
      how it can stray from being evidence-based. Publications related to umbilical
      cord coiling were retrieved and analysed with regard to how the umbilical coiling
      index was calculated, abnormal coiling was defined and reference ranges were
      constructed. Errors and other influences that can occur with the measurement of
      the length of the umbilical cord or of the number of coils can compromise the
      generation of the coiling index. Definitions of abnormal coiling are not
      consistent in the literature. Reference ranges defining hypocoiling or
      hypercoiling have not taken those potential errors or the possible effect of
      gestational age into account. Even the way numerical test results in anatomical
      pathology are generated, as illustrated by the umbilical coiling index, warrants
      a critical analysis into its evidence base to ensure that they are reproducible
      or free from errors.

PMID- 21080870
TI  - Performance measures for Australian laboratories reporting cervical cytology: a
      decade of data 1998-2008.
AB  - AIM: Performance measures for Australian laboratories reporting cervical cytology
      are a set of quantifiable measures relating to the profile and accuracy of
      reporting. This study reviews aggregate data collected over the ten years in
      which participation in the performance measures has been mandatory. METHODS:
      Laboratories submit annual data on performance measures relating to the profile
      of reporting, including reporting rates for technically unsatisfactory specimens,
      high grade or possible high grade abnormalities and abnormal reports. Cytology
      histology correlation data and review findings of negative smears reported from
      women with histological high grade disease are also collected. Suggested
      acceptable standards are set for each measure. This study reviews the aggregate
      data submitted by all laboratories for the years 1998-2008 and examines trends in
      reporting and the performance of laboratories against the suggested standards.
      RESULTS: The performance of Australian laboratories has shown continued
      improvement over the study period. There has been a fall in the proportion of
      laboratories with data outside the acceptable standard range in all performance
      measures. Laboratories are reporting a greater proportion of specimens as
      definite or possible high grade abnormality. This is partly attributable to an
      increase in the proportion of abnormal results classified as high grade or
      possible high grade abnormality. Despite this, the positive predictive value for
      high grade and possible high grade abnormalities has continued to rise.
      CONCLUSION: Performance measures for cervical cytology have provided a valuable
      addition to external quality assurance procedures in Australia. They have
      documented continued improvements in the aggregate performance, as well as
      providing benchmarking data and goals for acceptable performance for individual
      laboratories.

PMID- 21080871
TI  - Tumour expression of lymphangiogenic growth factors but not lymphatic vessel
      density is implicated in human cervical cancer progression.
AB  - AIMS: The aim of the study was to investigate the role of lymphangiogenesis in
      human cervical cancer progression. METHODS: The expression of VEGF-C, VEGF-D,
      VEGFR-3, podoplanin (D2-40), LYVE-1 and Prox-1 was studied by
      immunohistochemistry in 72 cases of invasive squamous cell carcinoma of the
      uterine cervix. For lymphatic endothelial markers lymphatic vessel density (LVD)
      was assessed. Correlations with lymphatic vessel invasion, nodal metastases,
      tumour grade, FIGO stage, and inflammation were also evaluated. RESULTS: VEGF-D
      expression significantly correlated with lymph node metastasis, lymphatic emboli
      and FIGO stage as well as with peritumoural LVD. A marginally significant
      correlation was also found between the expression of VEGF-C and prognostic
      parameters. Lymphatic tumour emboli were successfully identified using D2-40
      immunohistochemistry and peritumoural D2-40 LVD significantly correlated with
      lymphatic vessel invasion. However, LVD as assessed by multiple lymphatic markers
      was not associated with lymphatic metastasis. There was a significant correlation
      of Prox-1 and LYVE-1 LVD with the inflammatory stromal reaction. CONCLUSIONS:
      Although LVD as assessed by multiple lymphatic markers was not correlated with
      prognostic parameters, tumour expression of lymphangiogenic growth factors seems
      to be critically implicated in lymphatic metastasis and cervical carcinoma
      progression.

PMID- 21080872
TI  - Improved breast cancer biomarker detection through a simple, high frequency, low
      cost external proficiency testing program.
AB  - AIMS: We describe a simple, low cost, high frequency immunohistochemistry
      external proficiency testing program, and show how its use can lead to improved
      breast cancer biomarker detection. METHODS: Over a 30 month period in British
      Columbia, Canada, we used tissue microarray slides to follow the performance of
      twelve clinical laboratories in nine separate external proficiency testing runs.
      Sensitivity for detection of oestrogen receptor (ER), progesterone receptor (PR),
      and HER2 were calculated for each laboratory, biomarker, and run. RESULTS: Mean
      sensitivities for detection of ER, PR, and HER2 were 97.1%, 84.8%, and 90.7%,
      respectively. HER2 sensitivity improved over time, from 87.0% to 92.9% (p=0.04),
      with a trend towards improvement seen for PR (81.9-88.1%, p=0.13). ER
      sensitivities were high throughout the test period. Improvements occurred without
      mandating any specific laboratory changes. CONCLUSIONS: This simple, low cost,
      high frequency external proficiency testing program is highly sustainable and can
      be implemented in any multi-institutional group or region.

PMID- 21080873
TI  - Cytogenetic findings in Wilms' tumour: a single institute study.
AB  - AIMS: Cytogenetic abnormalities of Wilms' tumour (WT) treated in a single
      institution in Western Australia were reviewed. Correlation with histologic
      subtypes, stage, presence of nephrogenic rests and age of the patient at
      diagnosis were also evaluated. METHODS: 53 WT specimens were encountered between
      1995 and 2009. Tissue culture was obtained in 49 (92%) specimens. Reports
      documenting histopathological features of the tumour, stage and outcome were also
      retrieved. RESULTS: A total of 53 tumour specimens from 42 patients/cases were
      examined and staged in accordance with the National Wilms' Tumor Study (NWTS).
      Thirty-eight cases were unilateral (34 unifocal, 4 multifocal) and four were
      bilateral (2 multifocal). Fifty tumours showed favourable histology WT. One
      tumour was a cystic partially differentiated nephroblastoma (CPDN). Two tumours
      showed diffuse anaplasia. Eighteen specimens had nephrogenic rests, seven with
      perilobar rests, 10 with intralobar rests and one with both types of nephrogenic
      rests. Twelve WTs were assigned as stage 1, 22 as stage 2, 16 as stage 3, and two
      each for stages 4 and 5. For chromosomal analysis, 92% of the specimens yielded
      results, of which 70% showed abnormal karyotype and 22% displayed normal
      karyotypic findings. Hyperdiploidy was more common than hypodiploidy. The most
      common chromosomal gain involved chromosome 12. Low stage tumours tended to have
      abnormal karyotypes with hyperdiploidy and hypodiploidy being more common. There
      was no statistical correlation between abnormal karyotype and stage or abnormal
      karyotype and age group or abnormal karyotype and non-blastemal WT. Eleven (58%)
      tumours harbouring nephrogenic rests displayed an abnormal karyotype. 16q loss or
      der(16)t(1;16) were more common in younger patients but no association was made
      between this chromosomal abnormality and stage. Monosomy 22 and gain of 1q were
      more common in older patients. Furthermore, monosomy 22 tended to occur in
      tumours of earlier stage. No correlation between 11p deletions and age or stage
      was seen. CONCLUSIONS: WTs are karyotypically heterogeneous tumours. Conventional
      cytogenetic analysis of WTs still remains a useful technique to assist in the
      understanding of these tumours.

PMID- 21080874
TI  - Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological
      analysis of 72 cases.
AB  - AIM: Micropapillary carcinoma (MPC) of the bladder is an aggressive variant of
      urothelial carcinoma (UC). It is unknown if any amount of a micropapillary
      component justifies the diagnosis of MPC. It is also unknown if surface MPC also
      has aggressive potential. METHODS: We studied 72 patients with UC with a
      micropapillary component in transurethral resections of bladder (TURB) diagnosed
      between 1998 and 2008. Fifty-seven patients were treated with radical cystectomy.
      Tumours were classified according to pathological (pT) stage and percentage of
      MPC (<= 10%, 10-49%, 50-100%). This was correlated with clinical data and follow
      up. Significant factors in univariate analysis were entered into a multivariate
      analysis. RESULTS: In the TURB specimens, 12 had pTa, 33 pT1 and 27 pT2 tumours
      with 23% also displaying urothelial carcinoma in situ (CIS). On cystectomy, the
      MPC component was upstaged in 79% of cases. Twenty-five (35%) patients had
      metastases at presentation or nodal metastases at cystectomy and 27 patients
      (38%) died of disease. Mean survival was 17.8 months. Of 12 pTa MPC cases, eight
      were treated with cystectomy, all displaying invasive carcinoma including five
      (62%) with pT2-pT4 disease. Three (25%) of these patients died of disease. Seven
      patients had a MPC component of <10% all of whom had cystectomy. Six of these had
      invasive carcinoma including two (33%) with pT2-pT4 disease. One (15%) of these
      patients died of disease. On univariate analysis, the proportion of the MPC
      component on TURB and pathological stage predicted disease specific survival
      (p=0.01 and 0.004, respectively), while presence of CIS predicted recurrence
      (p=0.03). On multivariate analysis, CIS predicted recurrence (p=0.003); however,
      the proportion of MPC in TURB did not remain significant in predicting disease
      specific survival. The pathological stage of MPC remained significant in
      predicting disease specific survival (p=0.04). CONCLUSIONS: Any amount of MPC,
      even <10% is significant in urothelial carcinoma and should be reported. Surface
      MPC is associated with invasive carcinoma in most cases which can be high stage.
      Adequate sampling to include detrusor muscle is crucial in these cases.
      Associated CIS is important to be recognised and reported as this also impacts on
      clinical outcome.

PMID- 21080875
TI  - Loss of Raf-1 kinase inhibitory protein in pancreatic ductal adenocarcinoma.
AB  - AIMS: Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant
      metastatic suppressor in a variety of human cancers. The aim of this study was to
      evaluate RKIP expression and to determine its association with metastasis and
      prognostic significance in pancreatic cancer patients. METHODS:
      Immunohistochemical staining for RKIP was performed on 63 cases of pancreatic
      ductal adenocarcinoma (PDAC). We investigated whether RKIP expression correlated
      with clinicopathological parameters and patient outcomes. RESULTS: The islet
      cells, acinar cells and ductal epithelial cells of normal pancreas consistently
      showed strong RKIP immunoreactivity. In contrast, in PDAC, RKIP was lost in 57.1%
      (37/63) of cases. Loss of RKIP expression was significantly associated with the
      presence of nodal (p=0.001) and distant (p=0.010) metastases and a higher stage
      group (p=0.012). Univariate analysis for distant metastasis-free survival (DMFS)
      showed that the median DMFS of RKIP negative PDAC patients (10 months) was
      significantly shorter than that of RKIP positive PDAC patients (17 months;
      p=0.009). Multivariate analysis also revealed that loss of RKIP expression was an
      independent predictor of worse DMFS in PDAC patients (p=0.015). CONCLUSIONS: Our
      results strongly suggest that RKIP is a metastasis suppressor in PDAC.

PMID- 21080876
TI  - Abortive keratoacanthoma: a hitherto unrecognised variant.
AB  - AIMS: To study the histological features of abortive keratoacanthoma, a variant
      that has only recently been recognised. METHODS: A key word search of the
      database of our pathology practice was carried out for all keratoacanthomas (KAs)
      reported by one author (DW) over a 14-month period. These cases were then sorted
      into histological subtypes by age in decades. RESULTS: A total of 3465 cases of
      KA were reported over this period, of which 582 (16.8%) were of the so-called
      abortive type. Abortive KAs are characterised by rapid growth and subsequent
      lichenoid regression at an early stage in their evolution. Lichenoid changes
      extend for a variable distance beyond the lesion. CONCLUSIONS: Abortive KA is a
      hitherto unrecognised variant of KA which may be misdiagnosed as squamous cell
      carcinoma despite its distinctive features. Lichenoid regression, rather than
      terminal differentiation, is the main mechanism of its involution.

PMID- 21080877
TI  - Expression of platelet-derived growth factor-alpha receptor in human osteosarcoma
      is not a predictor of outcome.
AB  - AIMS: The aims of this study were to examine the prognostic relevance of platelet
      derived growth factor-alpha receptor (PDGFRA) expression in human osteosarcomas
      and to evaluate the mutation status of exon 12 and exon 18 of the PDGFRA gene.
      METHODS: PDGFRA expression was examined in 100 human osteosarcomas by
      immunohistochemistry using paraffin embedded tumour tissues, and capillary
      sequencing of genomic DNA was performed to search for mutations in exons 12 and
      18 of the PDGFRA gene. RESULTS: Ninety-six osteosarcomas showed PDGFRA expression
      ranging from 4% to 90% (mean 40%, median 37.5%, SD 27.11%). Furthermore, DNA
      sequence of exon 12 and exon 18 of the PDGFRA gene were not altered in 40 tumours
      with high PDGFRA expression. Overall and disease-free survival analysis did not
      reveal any differences between osteosarcoma patients with high PDGFRA expression
      and patients with low PDGFRA expression. CONCLUSIONS: The protein expression is
      not linked to mutations in exon 12 or exon 18 of PDGFRA gene. Therefore,
      treatment modalities based on the suppression of PDGFRA tyrosine kinase activity
      may need further investigation. PDGFRA expression is not a prognostic marker for
      osteosarcoma patients.

PMID- 21080878
TI  - A variant in microRNA-196a2 is associated with susceptibility to hepatocellular
      carcinoma in Chinese patients with cirrhosis.
AB  - AIMS: Cirrhosis is an important risk factor for hepatocellular carcinoma (HCC) in
      China, while little is known of the genetic susceptibility to
      hepatocarcinogenesis. Traditional approaches to identification of novel genetic
      predisposition genes have focused on protein encoding genes. There is evidence to
      suggest that microRNAs (miRNA) may play an important role in tumorigenesis.
      Recent studies have implicated that the rs11614913 SNP in miR-196a2 may be
      associated with susceptibility to lung cancer, congenital heart disease, breast
      cancer, as well as reduced survival in non-small cell lung cancer. This study
      aims to assess whether this functional polymorphism can influence susceptibility
      to and the progression of cirrhosis-related HCC. METHODS: 532 patients with
      hepatic cirrhosis (310 patients with HCC and 222 patients without HCC) were
      enrolled. DNA was extracted from blood specimens, and miR-196a2 polymorphism was
      genotyped by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). In addition, tumour tissues of liver (n=59) were obtained from the
      studied HCC patients for measurement of miR-196a expression levels. RESULTS: The
      frequency of the CC genotype among HCC patients was higher than that in the
      control group, implying that the cirrhotic patients with the CC genotype or C
      allele containing genotypes (CT and CC) may have a higher risk of HCC. However,
      in a subsequent analysis of the association between this polymorphism and
      clinicopathological characteristics, there was an association between rs11614913
      genotype and tumour size (p=0.046), but not with tumour number, grade, stage,
      invasiveness or Child-Pugh grade. In a genotype-phenotype correlation analysis
      using 59 tumour tissues of liver, rs11614913 CC or carrying at least one C allele
      was associated with significantly increased mature miR-196a expression (p=0.006
      or =0.002). CONCLUSIONS: Our results suggest, for the first time, that miR-196a2
      polymorphism may contribute to cirrhosis-related HCC susceptibility in Chinese
      patients through influencing mature miR-196a expression.

PMID- 21080880
TI  - Pistachio green brain discolouration associated with methylene blue use: an
      autopsy series.

PMID- 21080881
TI  - Dieulafoy's disease of the bronchus.

PMID- 21080879
TI  - A study of TNF-alpha-238 and -308 polymorphisms with different outcomes of
      persistent hepatitis B virus infection in China.
AB  - BACKGROUND: Two common functional polymorphisms in the promoter region of TNF
      alpha located at nucleotides -238 (rs361525) and -308 (rs1800629) have been
      reported to regulate the expression of tumour necrosis factor alpha (TNF-alpha)
      and to be associated with hepatitis B virus (HBV) infection related diseases.
      However, their frequencies and associations with outcomes of HBV infection are
      not clear. METHODS: We performed a genetic analysis of 956 Chinese Han subjects,
      who were divided into a HBV clearance group, an asymptomatic persistent infection
      group, a chronic hepatitis B group, two stages of liver cirrhosis (LC) groups,
      and three stages of hepatocellular carcinoma (HCC) groups to examine the
      relationship among HBV infection related diseases and these two single nucleotide
      polymorphisms (SNPs). RESULTS: The phenotype of polymorphism -238 in all study
      samples displayed no significant differences among the eight subgroups. The
      distribution of -308 phenotypes among the eight groups differed significantly.
      For females, compared with persistent infection, LC patients had a significantly
      higher A allele frequency, and the association with cirrhosis progression was
      significant. For males, there were statistically significant differences in
      allele distributions between the persistent infection group and the HCC group.
      The AG haplotype (-A308, -G238) was associated significantly with HCC
      development. CONCLUSIONS: The results of the present study indicate an
      association between rs1800629 and HBV related disease progression in the Chinese
      Han population. The association was different between genders, with the rs1800629
      A allele being a risk factor for female carriers to develop LC, and the allele
      being a risk factor for male carriers to develop HCC, especially in subjects with
      an alcohol abuse or cigarette smoking history.

PMID- 21080882
TI  - Coexistence of EBV associated nasopharyngeal undifferentiated carcinoma and
      gastric lymphoepithelioma-like carcinoma.

PMID- 21080884
TI  - Mucinous adenocarcinoma of the breast metastatic to the placenta.

PMID- 21080883
TI  - Transported papillary lesions of the breast in axillary lymph nodes: a report of
      two cases.

PMID- 21080885
TI  - Pagetoid involvement of vasitis nodosa by intratubular germ cell neoplasia
      unclassified.

PMID- 21080886
TI  - Intravascular leiomyosarcoma of the brachial artery: a case report.

PMID- 21080887
TI  - Myelinoid bodies in a patient with membranoproliferative glomerulonephritis.

PMID- 21080889
TI  - A case of plasmablastic lymphoma harbouring an IgH/MYC translocation in a HIV
      negative individual.

PMID- 21080888
TI  - Mutational analysis of pro-apoptotic ENDOG gene in common solid cancers and acute
      leukaemias.

PMID- 21080890
TI  - Lymphocyte vacuolation: clue to inherited metabolic disease.

PMID- 21080891
TI  - Centralised faecal blood testing for both screening and pathology requests.

PMID- 21080894
TI  - MotionTherapy@Home - First results of a clinical study with a novel robotic
      device for automated locomotion therapy at home.
AB  - In incomplete spinal cord injured subjects, task-oriented training regimes are
      applied for enhancement of neuroplasticity to improve gait capacity. However, a
      sufficient training intensity can only be achieved during the inpatient phase,
      which is getting shorter and shorter due to economic restrictions. In the
      clinical environment, complex and expensive robotic devices have been introduced
      to maintain the duration and the intensity of the training, but up to now only a
      few exist for continuation of automated locomotion training at home. For
      continuation of the automated locomotion training at home prototypes of the
      compact, pneumatically driven orthosis MoreGait have been realized, which
      generate the key afferent stimuli for activation of the spinal gait pattern
      generator. Artificial pneumatic muscles with excellent weight-to-force ratio and
      safety characteristics have been integrated as joint actuators. Additionally, a
      Stimulative Shoe for generation of the appropriate foot loading pattern has been
      developed without the need for verticalization of the user. The first results of
      the pilot study in eight chronic incomplete spinal cord injured subjects indicate
      that the home-based therapy is safe and feasible. The therapy related
      improvements of the walking capacity are in the range of locomotion robots used
      in clinical settings.

PMID- 21080895
TI  - Modeling of load transmission and distribution of deformation energy before and
      after healing of basal dental implants in the human mandible.
AB  - The purpose of this study was to present the amount and distribution of pressure,
      stress, and deformation energy when basal implants in the mandible are restored
      with a bridge which is loaded at two different stages of bone healing. The model
      geometry and material properties of the mandible were gained from CT scans of a
      human mandible. The material model used in this study defined bone as an
      inhomogeneous, linear elastic isotropic material. The masseter and temporal
      muscles were considered as rigid connections between the bones in typical
      positions and directions. The rotation axis was simulated in the
      temporomandibular joint. The loading force of 450 N was assumed to be in the
      middle between the left molar and left canine implant. In freshly operated bone,
      the total deformation energy is 30% higher than in healed bone, due to the
      defined energy absorbing soft bone areas. Approximately 90% of the deformation
      energy is absorbed by the bone, regardless of the healing state of the bone. The
      immediate rigid implant splinting distributes peak forces. To cope with these
      energies, the necessity of a reduction of total masticatory forces or the use of
      additional implants for force distribution should be considered individually.

PMID- 21080896
TI  - Winter health.

PMID- 21080897
TI  - Nobel prize to Robert Edwards.

PMID- 21080898
TI  - Medical and physical predictors of localized provoked vulvodynia.
AB  - Vulvodynia in young women is a significant clinical challenge. This overview
      focuses on localized provoked vulvodynia (LPV) with regard to medical and
      physical predictors of the condition. Several causative factors have been
      proposed and one major conceptual issue is the role of inflammation. Trauma to
      the vestibular mucosa causes an initial inflammatory response which may result in
      peripheral and central pain sensitization. In women with LPV, evidence of mucosal
      nerve fiber proliferation and enhanced systemic pain perception has been found. A
      dysfunction of the pelvic floor muscles is common and many patients also suffer
      from other bodily pain. In general, the level of scientific quality in published
      studies on vulvodynia is low. Further research on epidemiology, etiology and
      conduction of clinical trials with high evidence grade is desired.

PMID- 21080899
TI  - Clinical efficacy of mifepristone and misoprostol in second trimester pregnancy
      termination.
AB  - OBJECTIVE: the aim of this study was to evaluate factors affecting clinical
      effectiveness of 2nd trimester medical terminations using mifepristone and
      misoprostol combination. DESIGN: a retrospective observational study. POPULATION:
      ninety consecutive women who had undergone medical termination of pregnancy after
      12-24 weeks of gestation. METHODS: clinical data were collected from Oulu
      University Hospital patient records for the period between February 2003 and
      August 2005. The associations between patient characteristics and different
      outcomes were evaluated using standard statistical tests for correlation. MAIN
      OUTCOME MEASURES: the time elapsed from induction to successful abortion.
      RESULTS: the majority (94%) of women aborted successfully within 24 hours. Those
      who were considered day cases (no overnight hospitalization) were more likely to
      have a successful termination (p = 0.004), while those who were hospitalized for
      three or more days were more likely to have a complication (p = 0.046). Women
      with no previous live births or women with gestation >= 17 weeks required opiate
      analgesia more often (p = 0.019, p = 0.02, respectively). Induction to abortion
      time was shorter (p < 0.001) when pregnancy had lasted <17 weeks. Nulliparous
      women were more likely to have a longer induction-to-abortion interval (p <
      0.001) than uni- and multiparous women. Women with previous live births aborted
      more often within 8 hours than women with no previous births (p = 0.032).
      CONCLUSIONS: multiparous women and women with early gestation complete medical
      termination faster. Multiparity and shorter gestation time are also associated
      with lesser need for opiate analgesia, compared to nulliparous women or longer
      gestation time (>= 17 weeks).

PMID- 21080901
TI  - How to improve healthcare quality in uncomplicated pregnancy.

PMID- 21080900
TI  - The clinical impact of fetal magnetic resonance imaging on management of CNS
      anomalies in the second trimester of pregnancy.
AB  - OBJECTIVES: to evaluate the additional information of second trimester magnetic
      resonance imaging (MRI) compared to ultrasound in fetuses with identified or
      suspected central nervous system (CNS) anomalies and to study the clinical impact
      of the information on pregnancy management. DESIGN: prospective study during 2004
      2007. The fetal MRI examination was planned to be performed within 3 days after
      the ultrasound. Setting. Uppsala University hospital. MATERIAL: twenty-nine
      pregnant women in whom second trimester ultrasound identified or suspected fetal
      CNS anomalies. MAIN OUTCOME MEASURES: evaluation of the additional information
      gained from MRI and the consequence it had on pregnancy management. RESULTS: the
      mean interval between ultrasound and MRI was 1.6 days (range 0-7). In 16 fetuses
      (55%), MRI verified the ultrasound diagnosis but provided no additional
      information, while in 10 (35%) MRI gave additional information without changing
      the management. In 3 (10%), MRI provided additional information that changed the
      management of the pregnancy. Two of these women were obese. CONCLUSIONS: fetal
      MRI in the second trimester might be a clinically valuable adjunct to ultrasound
      for the evaluation of CNS anomalies, especially when ultrasound is inconclusive
      due to maternal obesity.

PMID- 21080902
TI  - Refractory fever with pancytopenia in postpartum and SLE-induced pancreatitis.

PMID- 21080907
TI  - Precipitation of kidney myosin IIA and IIB by freezing.
AB  - Actomyosin precipitation is a critical step in the purification of myosins. In
      this work, the objective was to precipitate rat kidney actomyosin and isolate
      myosin by freezing and thawing the soluble fraction. Kidney was homogenized in
      imidazole buffer, centrifuged at 45000 g for 30 min, and the supernatant was
      frozen at -20 degrees C for 48 h. The supernatant was thawed at 4 degrees C,
      centrifuged at 45000 g for 30 min and the precipitate washed twice with imidazole
      buffer pH 7.0 (with and without Triton X-100, respectively). The resulting
      precipitate presented a polypeptide profile in SDS/PAGE characteristic of
      actomyosin and expressed Mg- and K/EDTA-ATPase activity. The actomyosin complex
      was solubilized with ATP and Mg, and the main polypeptide, p200, was purified in
      a DEAE-Sepharose column. p200 was marked with anti-myosin II, co-sedimented with
      F-actin in the absence, but not in the presence, of ATP and was identified by
      MS/MS with a high Mascot score for myosin IIA. The analysis identified peptides
      exclusive of myosin IIB, but detected no peptides exclusive of myosin IIC.

PMID- 21080908
TI  - Mechanical stimuli on C2C12 myoblasts affect myoblast differentiation, focal
      adhesion kinase phosphorylation and galectin-1 expression: a proteomic approach.
AB  - Mechanical forces are crucial in the regulation of cell morphology and function.
      At the cellular level, these forces influence myoblast differentiation and
      fusion. In this study, we applied mechanical stimuli to embryonic muscle cells
      using magnetic microbeads, a method shown to apply stress to specific receptors
      on the cell surface. We showed that mechanical stimuli promote an increase in FAK
      (focal adhesion kinase) phosphorylation. In order to further shed light in the
      process of myoblast-induced differentiation by mechanical stimuli, we performed a
      proteomic analysis. Thirteen proteins were found to be affected by mechanical
      stimulation including galectin-1, annexin III and RhoGDI (Rho guanine-nucleotide
      dissociation inhibitor). In this study, we demonstrate how the combination of
      this method of mechanical stimuli and proteomic analysis can be a powerful tool
      to detect proteins that are potentially interacting in biochemical pathways or
      complex cellular mechanisms during the process of myoblast differentiation. We
      determined an increase in expression and changes in cellular localization of
      galectin-1 in mechanically stimulated myoblasts. A potential involvement of
      galectin-1 in myoblast differentiation is presented.

PMID- 21080909
TI  - Multiple factors influencing the release of hTERT mRNA from pancreatic cancer
      cell lines in in vitro culture.
AB  - Since telomerase expression is highly prevalent in human cancers, the
      quantitation of serum/plasma hTERT (human telomerase reverse transcriptase) mRNA
      levels may be useful for early detection of PCa (pancreatic cancer). To analyse
      the correspondence between exhTERT (extracellular hTERT) mRNA levels and hTERT
      expression, we designed a cell culture system to investigate factors modulating
      the extracellular levels of hTERT mRNA in media conditioned by eight PCa cell
      lines. We found that the level of exhTERT mRNA was dependent on cell growth rate.
      MIAPaCa-2, PANC-1, KLM-1 and PK-9 cells expressed high levels of exhTERT mRNA,
      independent of cell density, whereas proliferating PK-59, BxPC-3 and PK-45H cells
      released low levels of exhTERT mRNA. The augmented release of mRNA by spontaneous
      dead MIAPaCa-2 cells was further increased at postconfluence. In Capan-1 cells,
      low correspondence of marker was also due to RNase secretion. Upon reaching
      confluence, some PCa cell lines showed down-regulation of hTERT expression.
      Following cell-cell adhesion, as shown by E-cadherin engagement, PK-59 cells
      showed levels of extracellular message below the limits of detection, a loss not
      due to an increase in message degradation. These results suggest that the levels
      of exhTERT mRNA in the medium of PCa cell lines are altered not only in response
      to cell growth rate and cell destruction, but are responsive to extracellular
      cues such as RNases and cell density. A cell-free assay for exhTERT mRNA may
      therefore not be useful for early detection of PCa.

PMID- 21080910
TI  - Insulin-producing cells from human pancreatic islet-derived progenitor cells
      following transplantation in mice.
AB  - Stem/progenitor cells hold promise for alleviating/curing type 1 diabetes due to
      the capacity to differentiate into functional insulin-producing cells. The
      current study aims to assess the differentiation potential of human pancreatic
      IPCs (islet-derived progenitor cells). IPCs were derived from four human donors
      and subjected to more than 2000-fold expansion before turning into ICCs (islet
      like cell clusters). The ICCs expressed ISL-1 Glut2, PDX-1, ngn3, insulin,
      glucagon and somatostatin at the mRNA level and stained positive for insulin and
      glucagon by immunofluorescence. Following glucose challenge in vitro, C-peptide
      was detected in the sonicated ICCs, instead of in the conditioned medium. To
      examine the function of the cells in vivo, IPCs or ICCs were transplanted under
      the renal capsule of immunodeficient mice. One month later, 19 of 28 mice
      transplanted with ICCs and 4 of 14 mice with IPCs produced human C-peptide
      detectable in blood, indicating that the in vivo environment further facilitated
      the maturation of ICCs. However, among the hormone-positive mice, only 9 of 19
      mice with ICCs and two of four mice with IPCs were able to secrete C-peptide in
      response to glucose.

PMID- 21080911
TI  - Role of ZNRD1 (zinc ribbon domain-containing 1) in angiogenesis of leukaemia
      cells.
AB  - Here, we have first investigated the roles of ZNRD1 in angiogenesis of leukaemia.
      The leukaemia cell line K562 was transfected with the vector that included the
      full-length cDNA of ZNRD1, then the growth and angiogenesis of cells were
      detected. Up-regulation of ZNRD1 could significantly inhibit the growth of cells,
      reduce tumour microvessel densities and inhibit the VEGF (vascular endothelial
      growth factor) production. The results of human miRNA array and real-time PCR
      showed that ZNRD1 could significantly up-regulate the expression of miR-214 and
      down-regulate the expression of miR-296. Taken together, ZNRD1 might inhibit
      tumour angiogenesis and could be considered as a target for leukaemia therapy.

PMID- 21080913
TI  - The CRP genotype, serum levels and lung function in men: the Caerphilly
      Prospective Study.
AB  - Systemic CRP (C-reactive protein) has been associated with impaired lung
      function. A causal relationship would increase the value of CRP as both a
      diagnostic and therapeutic tool. We assessed the association between lung
      function parameters, circulating CRP and CRP polymorphisms using Mendelian
      randomization in efforts to attribute causality to known associations.
      Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced
      vital capacity) were determined in 2173 men participating in the Caerphilly
      Prospective Study. Lung function measures on 1021 participants were available at
      follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline,
      and three CRP polymorphisms were analysed. Haplotype analysis was performed.
      Serum CRP levels at baseline were inversely associated with contemporaneous FEV1
      and FVC as well as at follow-up (P<0.001) even after adjustment for conventional
      confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP
      polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however,
      there were no clear associations of the polymorphisms or haplotypes with lung
      function or with lung function decline. In conclusion, serum CRP was associated
      with lung function cross-sectionally; however, CRP polymorphisms were not
      associated with lung function or decline, suggesting that the CRP-lung function
      relationship is due to reverse causality, an unmeasured confounding factor or
      only has a modest causal effect.

PMID- 21080914
TI  - Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of
      alpha-1 antitrypsin.
AB  - The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic
      exotoxin B) is important for the invasive potential of the bacteria, but its
      production is down-regulated following systemic infection. This prompted us to
      investigate if SpeB potentiated the host immune response after systemic
      spreading. Addition of SpeB to human plasma increased plasma-mediated bacterial
      killing and prolonged coagulation time through the intrinsic pathway of
      coagulation. This effect was independent of the enzymatic activity of SpeB and
      was mediated by a non-covalent medium-affinity binding and modification of the
      serpin A1AT (alpha-1 antitrypsin). Consequently, addition of A1AT to plasma
      increased bacterial survival. Sequestration of A1AT by SpeB led to enhanced
      contact system activation, supported by increased bacterial growth in
      prekallikrein deficient plasma. In a mouse model of systemic infection,
      administration of SpeB reduced significantly bacterial dissemination. The
      findings reveal an additional layer of complexity to host-microbe interactions
      that may be of benefit in the treatment of severe bacterial infections.

PMID- 21080915
TI  - The characterization of human adenylate kinases 7 and 8 demonstrates differences
      in kinetic parameters and structural organization among the family of adenylate
      kinase isoenzymes.
AB  - Differences in expression profiles, substrate specificities, kinetic properties
      and subcellular localization among the AK (adenylate kinase) isoenzymes have been
      shown to be important for maintaining a proper adenine nucleotide composition for
      many different cell functions. In the present study, human AK7 was characterized
      and its substrate specificity, kinetic properties and subcellular localization
      determined. In addition, a novel member of the human AK family, with two
      functional domains, was identified and characterized and assigned the name AK8.
      AK8 is the second known human AK with two complete and active AK domains within
      its polypeptide chain, a feature that has previously been shown for AK5. The full
      length AK8, as well as its two domains AK8p1 and AK8p2, all showed similar AK
      enzyme activity. AK7, full-length AK8, AK8p1 and AK8p2 phosphorylated AMP, CMP,
      dAMP and dCMP with ATP as the phosphate donor, and also AMP, CMP and dCMP with
      GTP as the phosphate donor. Both AK7 and full-length AK8 showed highest affinity
      for AMP with ATP as the phosphate donor, and proved to be more efficient in AMP
      phosphorylation as compared with the major cytosolic isoform AK1. Expression of
      the proteins fused with green fluorescent protein demonstrated a cytosolic
      localization for both AK7 and AK8.

PMID- 21080916
TI  - Effective radiation attenuation calibration for breast density: compression
      thickness influences and correction.
AB  - BACKGROUND: Calibrating mammograms to produce a standardized breast density
      measurement for breast cancer risk analysis requires an accurate spatial measure
      of the compressed breast thickness. Thickness inaccuracies due to the nominal
      system readout value and compression paddle orientation induce unacceptable
      errors in the calibration. METHOD: A thickness correction was developed and
      evaluated using a fully specified two-component surrogate breast model. A
      previously developed calibration approach based on effective radiation
      attenuation coefficient measurements was used in the analysis. Water and oil were
      used to construct phantoms to replicate the deformable properties of the breast.
      Phantoms consisting of measured proportions of water and oil were used to
      estimate calibration errors without correction, evaluate the thickness
      correction, and investigate the reproducibility of the various calibration
      representations under compression thickness variations. RESULTS: The average
      thickness uncertainty due to compression paddle warp was characterized to within
      0.5 mm. The relative calibration error was reduced to 7% from 48-68% with the
      correction. The normalized effective radiation attenuation coefficient (planar)
      representation was reproducible under intra-sample compression thickness
      variations compared with calibrated volume measures. CONCLUSION: Incorporating
      this thickness correction into the rigid breast tissue equivalent calibration
      method should improve the calibration accuracy of mammograms for risk assessments
      using the reproducible planar calibration measure.

PMID- 21080917
TI  - Epithelial N-cadherin and nuclear beta-catenin are up-regulated during early
      development of human lung.
AB  - BACKGROUND: The aim of this study was to analyze the cell-specific expression of
      E- and N-cadherin and beta-catenin in developing human lung tissues from 12 to 40
      weeks of gestation. METHODS: Forty-seven cases of developing human lung including
      pseudoglandular, canalicular, saccular and alveolar periods were analyzed by
      immunohistochemistry for E- and N-cadherin and beta-catenin and twenty-one cases
      were also investigated by RT-PCR for E- and N-cadherin and beta-catenin. For
      identifying the lung cells, the sections were also stained with antibodies
      against thyroid transcription factor-1 (TTF-1) and caveolin-1. Normal adult lung
      tissue was used as a control. E-cadherin was strongly expressed in epithelium of
      bronchi and large bronchioles from week 12 onwards and it was also positive in
      alveoli in pretype II cells and type II cells. N-cadherin was present in most of
      the epithelial cells of bronchi and the largest bronchioles during the pseudo
      glandular and canalicular periods. N-cadherin was not detected in epithelium of
      developing alveoli. beta-catenin was strongly membrane-bound and positively
      expressed in bronchial epithelium from week 12 to week 40; it showed nuclear
      positivity in both developing airway epithelium and in the cells underneath the
      epithelium during pseudo-glandular period and to a lesser degree also in the
      canalicular period. beta-catenin was positive in pretype II cells as well as in
      type I and type II pneumocytes within alveoli. RT-PCR analyses revealed
      detectable amounts of RNAs of E- and N-cadherin and beta-catenin in all cases
      studied. The amounts of RNAs were higher in early stages of gestation.
      CONCLUSIONS: E-cadherin is widely expressed in bronchial and alveolar epithelial
      cells. N-cadherin exhibit extensive epithelial positivity in bronchial epithelial
      cells during early lung development. The presence of beta-catenin was observed in
      several cell types with a distinct location in tissue and cells in various
      gestational stages, indicating that it possesses several roles during lung
      development. The expressions of protein and mRNAs of E- and N-cadherin and beta
      catenin were higher in early gestation compared to of the end. Moreover, the
      expressions of these factors were higher during the lung development than in the
      adult human lung.

PMID- 21080918
TI  - The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells
      and increases the short term effects of ionizing radiation.
AB  - BACKGROUND AND PURPOSE: The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is
      frequently deregulated in prostate cancer and associated with neoplastic
      transformation, malignant progression, and enhanced resistance to classical
      chemotherapy and radiotherapy. Thus, it is a promising target for therapeutic
      intervention. In the present study, the cytotoxic action of the Akt inhibitor
      Erufosine (ErPC3) was analyzed in prostate cancer cells and compared to the
      cytotoxicity of the PI3K inhibitor LY294002. Moreover, the efficacy of combined
      treatment with Akt inhibitors and ionizing radiation in prostate cancer cells was
      examined. MATERIALS AND METHODS: Prostate cancer cell lines PC3, DU145, and LNCaP
      were treated with ErPC3 (1-100 uM), LY294002 (25-100 uM), irradiated (0-10 Gy),
      or subjected to combined treatments. Cell viability was determined by the WST-1
      assay. Apoptosis induction was analyzed by flow cytometry after staining with
      propidium iodide in a hypotonic citrate buffer, and by Western blotting using
      antibodies against caspase-3 and its substrate PARP. Akt activity and regulation
      of the expression of Bcl-2 family members and key downstream effectors involved
      in apoptosis regulation were examined by Western blot analysis. RESULTS: The Akt
      inhibitor ErPC3 exerted anti-neoplastic effects in prostate cancer cells, however
      with different potency. The anti-neoplastic action of ErPC3 was associated with
      reduced phosphoserine 473-Akt levels and induction of apoptosis. PC3 and LNCaP
      prostate cancer cells were also sensitive to treatment with the PI3K inhibitor
      LY294002. However, the ErPC3-sensitive PC3-cells were less susceptible to
      LY294002 than the ErPC3-refractory LNCaP cells. Although both cell lines were
      largely resistant to radiation-induced apoptosis, both cell lines showed higher
      levels of apoptotic cell death when ErPC3 was combined with radiotherapy.
      CONCLUSIONS: Our data suggest that constitutive Akt activation and survival are
      controlled by different different molecular mechanisms in the two prostate cancer
      cell lines - one which is sensitive to the Akt-inhibitor ErPC3 and one which is
      more sensitive to the PI3K-inhibitor LY294002. Our findings underline the
      importance for the definition of predictive biomarkers that allow the selection
      patients that may benefit from the treatment with a specific signal transduction
      modifier.

PMID- 21080919
TI  - Sexual behaviour does not reflect HIV-1 prevalence differences: a comparison
      study of Zimbabwe and Tanzania.
AB  - BACKGROUND: Substantial heterogeneity in HIV prevalence has been observed within
      sub-Saharan Africa. It is not clear which factors can explain these differences.
      Our aim was to identify risk factors that could explain the large differences in
      HIV-1 prevalence among pregnant women in Harare, Zimbabwe, and Moshi, Tanzania.
      METHODS: Cross-sectional data from a two-centre study that enrolled pregnant
      women in Harare (N = 691) and Moshi (N = 2654) was used. Consenting women were
      interviewed about their socio-demographic background and sexual behaviour, and
      tested for presence of sexually transmitted infections and reproductive tract
      infections. Prevalence distribution of risk factors for HIV acquisition and
      spread were compared between the two areas. RESULTS: The prevalence of HIV-1
      among pregnant women was 26% in Zimbabwe and 7% in Tanzania. The HIV prevalence
      in both countries rises constantly with age up to the 25-30 year age group. After
      that, it continues to rise among Zimbabwean women, while it drops for Tanzanian
      women. Risky sexual behaviour was more prominent among Tanzanians than
      Zimbabweans. Mobility and such infections as HSV-2, trichomoniasis and bacterial
      vaginosis were more prevalent among Zimbabweans than Tanzanians. Reported male
      partner circumcision rates between the two countries were widely different, but
      the effect of male circumcision on HIV prevalence was not apparent within the
      populations. CONCLUSIONS: The higher HIV-1 prevalence among pregnant women in
      Zimbabwe compared with Tanzania cannot be explained by differences in risky
      sexual behaviour: all risk factors tested for in our study were higher for
      Tanzania than Zimbabwe. Non-sexual transmission of HIV might have played an
      important role in variation of HIV prevalence. Male circumcision rates and
      mobility could contribute to the rate and extent of spread of HIV in the two
      countries.

PMID- 21080920
TI  - Comparison of intra-articular injections of hyaluronic acid and corticosteroid in
      the treatment of osteoarthritis of the hip in comparison with intra-articular
      injections of bupivacaine. Design of a prospective, randomized, controlled study
      with blinding of the patients and outcome assessors.
AB  - BACKGROUND: Although intra-articular hyaluronic acid is well established as a
      treatment for osteoarthritis of the knee, its use in hip osteoarthritis is not
      based on large randomized controlled trials. There is a need for more rigorously
      designed studies on hip osteoarthritis treatment as this subject is still very
      much under debate. METHODS/DESIGN: Randomized, controlled trial with a three
      armed, parallel-group design. Approximately 315 patients complying with the
      inclusion and exclusion criteria will be randomized into one of the following
      treatment groups: infiltration of the hip joint with hyaluronic acid, with a
      corticosteroid or with 0.125% bupivacaine.The following outcome measure
      instruments will be assessed at baseline, i.e. before the intra-articular
      injection of one of the study products, and then again at six weeks, 3 and 6
      months after the initial injection: Pain (100 mm VAS), Harris Hip Score and HOOS,
      patient assessment of their clinical status (worse, stable or better then at the
      time of enrollment) and intake of pain rescue medication (number per week). In
      addition patients will be asked if they have complications/adverse events. The
      six-month follow-up period for all patients will begin on the date the first
      injection is administered. DISCUSSION: This randomized, controlled, three-arm
      study will hopefully provide robust information on two of the intra-articular
      treatments used in hip osteoarthritis, in comparison to bupivacaine. TRIAL
      REGISTRATION: NCT01079455.

PMID- 21080921
TI  - Congenital abnormalities and multiple sclerosis.
AB  - BACKGROUND: There is a strong maternal parent-of-origin effect in determining
      susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal
      intrauterine milieu leading to impaired fetal development could plausibly also
      result in increased susceptibility to MS. A possible marker for this intrauterine
      insult is the presence of a non-fatal congenital anomaly. METHODS: We
      investigated whether or not congenital anomalies are associated with MS in a
      population-based cohort. We identified 7063 MS index cases and 2655 spousal
      controls with congenital anomaly information from the Canadian Collaborative
      Project on Genetic Susceptibility to MS (CCPGSMS). RESULTS: The frequency of
      congenital anomalies were compared between index cases and controls. No
      significant differences were found. CONCLUSIONS: Congenital anomalies thus do not
      appear to be associated with MS. However, we did not have complete data on types
      and severity of congenital anomalies or on maternal birth history and thus this
      study should be regarded as preliminary.

PMID- 21080922
TI  - "pp65 antigenemia and real time polymerase chain reaction (PCR) based-study to
      determine the prevalence of human cytomegalovirus (HCMV) in kidney donors and
      recipients with follow-up studies".
AB  - BACKGROUND: The present study was undertaken to determine the rate of occurrence
      of Human cytomegalovirus (HCMV) among kidney transplant recipients and donors by
      application of direct detection methods and to understand HCMV infection/disease
      development among transplanted patients as a prospective study. RESULTS:
      Peripheral blood samples collected from 76 kidney donors and 76 recipients from
      September 2007 to August 2009 were subjected to pp65 antigenemia and Quantitative
      real-time PCR (qRT-PCR) assays. Data were analyzed under Group A, B and C. Group
      A was further divided into sub-groups I, II, III, IV, and V for better
      understanding. Three, one and two donors in sub-group I, III, IV of Group A
      tested positive for real time PCR respectively. One recipient from group III
      tested positive for HCMV by qRT- PCR prior transplantation and remained positive
      one month post-transplantation. Three other recipients, tested negative prior to
      transplantation became positive a month after transplantation. Group B consisted
      of 18 donor-recipient pairs and one of the donor tested positive for HCMV by qRT
      PCR. Eight recipients tested positive for HCMV one month after transplantation.
      The pp65 positivity and HCMV DNA load was high among group C recipients who
      mostly had symptoms of active disease. Significantly high values of pp65
      antigenemia were observed among recipients of sub-group II (non-parametric chi
      square test p = 0.007). Positive correlation between pp65 antigenemia and qRT-PCR
      value was observed. Thirty three of the recipients with disease treated with
      Valgancyclovir showed improved clinical outcome. CONCLUSION: Our study showed
      that a significant proportion of kidney recipients develop HCMV infection
      following renal transplantation in spite of the absence of HCMV among donors.
      pp65 antigenemia assay and qRT- PCR methods can be applied to detect HCMV among
      kidney donors and recipients to monitor development of disease and these assays
      were predicative of HCMV infection among them. Clinical resistant to
      valganciclovir was not observed.

PMID- 21080923
TI  - Self-reported tobacco smoking practices among medical students and their
      perceptions towards training about tobacco smoking in medical curricula: A cross
      sectional, questionnaire survey in Malaysia, India, Pakistan, Nepal, and
      Bangladesh.
AB  - BACKGROUND: Tobacco smoking issues in developing countries are usually taught non
      systematically as and when the topic arose. The World Health Organisation and
      Global Health Professional Student Survey (GHPSS) have suggested introducing a
      separate integrated tobacco module into medical school curricula. Our aim was to
      assess medical students' tobacco smoking habits, their practices towards
      patients' smoking habits and attitude towards teaching about smoking in medical
      schools. METHODS: A cross-sectional questionnaire survey was carried out among
      final year undergraduate medical students in Malaysia, India, Nepal, Pakistan,
      and Bangladesh. An anonymous, self-administered questionnaire included items on
      demographic information, students' current practices about patients' tobacco
      smoking habits, their perception towards tobacco education in medical schools on
      a five point Likert scale. Questions about tobacco smoking habits were adapted
      from GHPSS questionnaire. An 'ever smoker' was defined as one who had smoked
      during lifetime, even if had tried a few puffs once or twice. 'Current smoker'
      was defined as those who had smoked tobacco product on one or more days in the
      preceding month of the survey. Descriptive statistics were calculated. RESULTS:
      Overall response rate was 81.6% (922/1130). Median age was 22 years while 50.7%
      were males and 48.2% were females. The overall prevalence of 'ever smokers' and
      'current smokers' was 31.7% and 13.1% respectively. A majority (> 80%) of
      students asked the patients about their smoking habits during clinical
      postings/clerkships. Only a third of them did counselling, and assessed the
      patients' willingness to quit. Majority of the students agreed about doctors'
      role in tobacco control as being role models, competence in smoking cessation
      methods, counseling, and the need for training about tobacco cessation in medical
      schools. About 50% agreed that current curriculum teaches about tobacco smoking
      but not systematically and should be included as a separate module. Majority of
      the students indicated that topics about health effects, nicotine addiction and
      its treatment, counselling, prevention of relapse were important or very
      important in training about tobacco smoking. CONCLUSION: Medical educators should
      consider revising medical curricula to improve training about tobacco smoking
      cessation in medical schools. Our results should be supported by surveys from
      other medical schools in developing countries of Asia.

PMID- 21080924
TI  - Feasibility and safety of high-dose adenosine perfusion cardiovascular magnetic
      resonance.
AB  - INTRODUCTION: Adenosine is the most widely used vasodilator stress agent for
      cardiovascular magnetic resonance (CMR) perfusion studies. With the standard dose
      of 140 mcg/kg/min some patients fail to demonstrate characteristic haemodynamic
      changes: a significant increase in heart rate (HR) and mild decrease in systolic
      blood pressure (SBP). Whether an increase in the rate of adenosine infusion would
      improve peripheral and, likely, coronary vasodilatation in those patients is
      unknown. The aim of the present study was to assess the tolerance and safety of a
      high-dose adenosine protocol in patients with inadequate haemodynamic response to
      the standard adenosine protocol when undergoing CMR perfusion imaging. METHODS:
      98 consecutive patients with known or suspected coronary artery disease (CAD)
      underwent CMR perfusion imaging at 1.5 Tesla. Subjects were screened for
      contraindications to adenosine, and an electrocardiogram was performed prior to
      the scan. All patients initially received the standard adenosine protocol (140
      mcg/kg/min for at least 3 minutes). If the haemodynamic response was inadequate
      (HR increase < 10 bpm or SBP decrease < 10 mmHg) then the infusion rate was
      increased up to a maximum of 210 mcg/kg/min (maximal infusion duration 7
      minutes). RESULTS: All patients successfully completed the CMR scan. Of a total
      of 98 patients, 18 (18%) did not demonstrate evidence of a significant increase
      in HR or decrease in SBP under the standard adenosine infusion rate. Following
      the increase in the rate of infusion, 16 out of those 18 patients showed an
      adequate haemodynamic response. One patient of the standard infusion group and
      two patients of the high-dose group developed transient advanced AV block.
      Significantly more patients complained of chest pain in the high-dose group (61%
      vs. 29%, p = 0.009). On multivariate analysis, age > 65 years and ejection
      fraction < 57% were the only independent predictors of blunted haemodynamic
      responsiveness to adenosine. CONCLUSIONS: A substantial number of patients do not
      show adequate peripheral haemodynamic response to standard-dose adenosine stress
      during perfusion CMR imaging. Age and reduced ejection fraction are predictors of
      inadequate response to standard dose adenosine. A high-dose adenosine protocol
      (up to 210 mcg/kg/min) is well tolerated and results in adequate haemodynamic
      response in nearly all patients.

PMID- 21080926
TI  - To what extent could performance-based schemes help increase the effectiveness of
      prevention of mother-to-child transmission of HIV (PMTCT) programs in resource
      limited settings? A summary of the published evidence.
AB  - BACKGROUND: In resource-limited settings, HIV/AIDS remains a serious threat to
      the social and physical well-being of women of childbearing age, pregnant women,
      mothers and infants. DISCUSSION: In sub-Saharan African countries with high
      prevalence rates, pediatric HIV/AIDS acquired through mother-to-child
      transmission (MTCT) can in largely be prevented by using well-established
      biomedical interventions. Logistical and socio-cultural barriers continue,
      however, to undermine the successful prevention of MTCT (PMTCT). In this paper,
      we review reports on maternal, neonatal and child health, as well as HIV care and
      treatment services that look at program incentives. SUMMARY: These studies
      suggest that comprehensive PMTCT strategies aiming to maximize health-worker
      motivation in developing countries must involve a mix of both financial and non
      financial incentives. The establishment of robust ethical and regulatory
      standards in public-sector HIV care centers could reduce barriers to PMTCT
      service provision in sub-Saharan Africa and help them in achieving universal
      PMTCT targets.

PMID- 21080925
TI  - Therapeutic potential of human umbilical cord mesenchymal stem cells in the
      treatment of rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune
      disease, characterized by synovium inflammation and articular destruction. Bone
      marrow mesenchymal stem cells (MSCs) could be effective in the treatment of
      several autoimmune diseases. However, there has been thus far no report on
      umbilical cord (UC)-MSCs in the treatment of RA. Here, potential
      immunosuppressive effects of human UC-MSCs in RA were evaluated. METHODS: The
      effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T
      cells in RA patients were explored. The possible molecular mechanism mediating
      this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors
      to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2),
      transforming growth factor beta1 (TGF-beta1) and interleukin 10 (IL-10). The
      therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced
      arthritis (CIA) in a mouse model were explored. RESULTS: In vitro, UC-MSCs were
      capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and
      TGF-beta1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were
      also significantly suppressed. On the other hand, UC-MSCs induced
      hyporesponsiveness of T cells mediated by PGE2, TGF-beta1 and NO and UC-MSCs
      could promote the expansion of CD4(+) Foxp3(+) regulatory T cells from RA
      patients. More importantly, systemic infusion of human UC-MSCs reduced the
      severity of CIA in a mouse model. Consistently, there were reduced levels of
      proinflammatory cytokines and chemokines (TNF-alpha, IL-6 and monocyte
      chemoattractant protein-1) and increased levels of the anti
      inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice.
      Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA.
      CONCLUSIONS: In conclusion, human UC-MSCs suppressed the various inflammatory
      effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA
      in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA.
      In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the
      participation of Tregs.

PMID- 21080927
TI  - Pellicle formation in Shewanella oneidensis.
AB  - BACKGROUND: Although solid surface-associated biofilm development of S.
      oneidensis has been extensively studied in recent years, pellicles formed at the
      air-liquid interface are largely overlooked. The goal of this work was to
      understand basic requirements and mechanism of pellicle formation in S.
      oneidensis. RESULTS: We demonstrated that pellicle formation can be completed
      when oxygen and certain cations were present. Ca(II), Mn(II), Cu(II), and Zn(II)
      were essential for the process evidenced by fully rescuing pellicle formation of
      S. oneidensis from the EDTA treatment while Mg (II), Fe(II), and Fe(III) were
      much less effective. Proteins rather than DNA were crucial in pellicle formation
      and the major exopolysaccharides may be rich in mannose. Mutational analysis
      revealed that flagella were not required for pellicle formation but flagellum
      less mutants delayed pellicle development substantially, likely due to reduced
      growth in static media. The analysis also demonstrated that AggA type I secretion
      system was essential in formation of pellicles but not of solid surface
      associated biofilms in S. oneidensis. CONCLUSION: This systematic
      characterization of pellicle formation shed lights on our understanding of
      biofilm formation in S. oneidensis and indicated that the pellicle may serve as a
      good research model for studying bacterial communities.

PMID- 21080928
TI  - Commuting and health in Cambridge: a study of a 'natural experiment' in the
      provision of new transport infrastructure.
AB  - BACKGROUND: Modifying transport infrastructure to support active travel (walking
      and cycling) could help to increase population levels of physical activity.
      However, there is limited evidence for the effects of interventions in this
      field, and to the best of our knowledge no study has convincingly demonstrated an
      increase in physical activity directly attributable to this type of intervention.
      We have therefore taken the opportunity presented by a 'natural experiment' in
      Cambridgeshire, UK to establish a quasi-experimental study of the effects of a
      major transport infrastructural intervention on travel behaviour, physical
      activity and related wider health impacts. DESIGN AND METHODS: The Commuting and
      Health in Cambridge study comprises three main elements: a cohort study of adults
      who travel to work in Cambridge, using repeated postal questionnaires and basic
      objective measurement of physical activity using accelerometers; in-depth
      quantitative studies of physical activity energy expenditure, travel and movement
      patterns and estimated carbon emissions using household travel diaries, combined
      heart rate and movement sensors and global positioning system (GPS) receivers;
      and a longitudinal qualitative interview study to elucidate participants'
      attitudes, experiences and practices and to understand how environmental and
      social factors interact to influence travel behaviour, for whom and in what
      circumstances. The impacts of a specific intervention - the opening of the
      Cambridgeshire Guided Busway - and of other changes in the physical environment
      will be examined using a controlled quasi-experimental design within the overall
      cohort dataset. DISCUSSION: Addressing the unresolved research and policy
      questions in this area is not straightforward. The challenges include those of
      effectively combining different disciplinary perspectives on the research
      problems, developing common methodological ground in measurement and evaluation,
      implementing robust quantitative measurement of travel and physical activity
      behaviour in an unpredictable 'natural experiment' setting, defining exposure to
      the intervention, defining controls, and conceptualising an appropriate
      longitudinal analytical strategy.

PMID- 21080931
TI  - Functional relations between locomotor performance traits in spiders and
      implications for evolutionary hypotheses.
AB  - BACKGROUND: Locomotor performance in ecologically relevant activities is often
      linked to individual fitness. Recent controversy over evolution of extreme sexual
      size dimorphism (SSD) in spiders centres on the relationship between size and
      locomotor capacity in males. Advantages for large males running over horizontal
      surfaces and small males climbing vertically have been proposed. Models have
      implicitly treated running and climbing as functionally distinct activities and
      failed to consider the possibility that they reflect common underlying
      capacities. FINDINGS: We examine the relationship between maximum climbing and
      running performance in males of three spider species. Maximum running and
      climbing speeds were positively related in two orb-web spiders with high SSD
      (Argiope keyserlingi and Nephila plumipes), indicating that for these species
      assays of running and climbing largely reveal the same underlying capacities.
      Running and climbing speeds were not related in a jumping spider with low SSD
      (Jacksonoides queenslandica). We found no evidence of a performance trade-off
      between these activities. CONCLUSIONS: In the web-spiders A. keyserlingi and N.
      plumipes good runners were also good climbers. This indicates that climbing and
      running largely represent a single locomotor performance characteristic in these
      spiders, but this was not the case for the jumping spider J. queenslandica. There
      was no evidence of a trade-off between maximum running and climbing speeds in
      these spiders. We highlight the need to establish the relationship between
      apparently disparate locomotor activities when testing alternative hypotheses
      that yield predictions about different locomotor activities. Analysis of slopes
      suggests greater potential for an evolutionary response on performance in the
      horizontal compared to vertical context in these spiders.

PMID- 21080929
TI  - Optimizing pentose utilization in yeast: the need for novel tools and approaches.
AB  - Hexose and pentose cofermentation is regarded as one of the chief obstacles
      impeding economical conversion of lignocellulosic biomass to biofuels. Over time,
      successful application of traditional metabolic engineering strategy has produced
      yeast strains capable of utilizing the pentose sugars (especially xylose and
      arabinose) as sole carbon sources, yet major difficulties still remain for
      engineering simultaneous, exogenous sugar metabolism. Beyond catabolic pathways,
      the focus must shift towards non-traditional aspects of cellular engineering such
      as host molecular transport capability, catabolite sensing and stress response
      mechanisms. This review highlights the need for an approach termed 'panmetabolic
      engineering', a new paradigm for integrating new carbon sources into host
      metabolic pathways. This approach will concurrently optimize the interdependent
      processes of transport and metabolism using novel combinatorial techniques and
      global cellular engineering. As a result, panmetabolic engineering is a whole
      pathway approach emphasizing better pathways, reduced glucose-induced repression
      and increased product tolerance. In this paper, recent publications are reviewed
      in light of this approach and their potential to expand metabolic engineering
      tools. Collectively, traditional approaches and panmetabolic engineering enable
      the reprogramming of extant biological complexity and incorporation of exogenous
      carbon catabolism.

PMID- 21080930
TI  - Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor
      positive and negative BRCA1-associated breast cancers.
AB  - INTRODUCTION: The majority of breast cancers that occur in BRCA1 mutation
      carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has
      been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the
      cell of origin of these tumors. However, approximately 20% of breast cancers that
      develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to
      develop as BRCA1 carriers age, suggesting that they may be incidental and
      unrelated to BRCA1 deficiency. The purpose of this study was to compare the
      prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+
      and ER- breast cancers that have occurred in BRCA1 carriers and to determine
      whether age at diagnosis or any pathologic features or biomarkers predict for
      loss of wt BRCA1 in these breast cancers. METHODS: Relative amounts of mutated
      and wt BRCA1 DNA were measured by quantitative polymerase chain reaction
      performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER-
      invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation
      was determined on all cancers in which sufficient DNA was available. Immunostains
      for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53
      were performed on paraffin sections from tissue microarrays containing these
      cancers. RESULTS: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1
      associated cancers (81.0% vs 88.6%, respectively; P = 0.53). One of nine cancers
      tested that retained wt BRCA1 demonstrated BRCA1 gene methylation. Age at
      diagnosis was not significantly different between first invasive ER+ BRCA1 breast
      cancers with and without loss of wt BRCA1 (mean age 45.2 years vs 50.1 years,
      respectively; P = 0.51). ER+ BRCA1 cancers that retained wt BRCA1 were
      significantly more likely than those that lost wt BRCA1 to have a low mitotic
      rate (odds ratio (OR), 5.16; 95% CI, 1.91 to infinity). BRCA1 cancers with loss
      of wt BRCA1 were more likely to express basal cytokeratins CK 5/6 or 14 (OR 4.7;
      95% CI, 1.85 to infinity). CONCLUSIONS: We found no difference in the prevalence
      of loss of wt BRCA1 between ER+ and ER- invasive BRCA1-associated breast cancers.
      Our findings suggest that many of the newer therapies for BRCA1 breast cancers
      designed to exploit the BRCA1 deficiency in these cancers may also be effective
      in ER+ cancers that develop in this population.

PMID- 21080932
TI  - Augmented plasma microparticles during acute Plasmodium vivax infection.
AB  - BACKGROUND: In the last few years, the study of microparticles (MPs)--submicron
      vesicles released from cells upon activation or apoptosis--has gained growing
      interest in the field of inflammation and in infectious diseases. Their role in
      the human malaria parasite Plasmodium vivax remains unexplored. Because acute
      vivax malaria has been related to pro-inflammatory responses, the main hypothesis
      investigated in this study was that Plasmodium vivax infection is associated with
      elevated levels of circulating MPs, which may play a role during acute disease in
      non-immune patients. METHODS: Plasma MPs were analysed among thirty-seven
      uncomplicated P. vivax infections from an area of unstable malaria transmission
      in the Brazilian Amazon. The MP phenotype was analysed by flow cytometry using
      the classical MP marker, annexin, and fluorochrome-labeled monoclonal antibodies
      against specific cell surface markers. The frequencies of plasma MPs in P. vivax
      patients (n=37) were further compared to malaria-unexposed controls (n=15) and
      ovarian carcinoma patients (n=12), a known MPs-inducing disease non-related to
      malaria. RESULTS: The frequencies of plasma circulating MPs were markedly
      increased in P. vivax patients, as compared to healthy age-matched malaria
      unexposed controls. Although platelets, erythrocytes and leukocytes were the main
      cellular sources of MPs during vivax malaria, platelet derived-MPs (PMPs)
      increased in a linear fashion with the presence of fever at the time of blood
      collection (beta=0.06, p<0.0001) and length of acute symptoms (beta=0.36,
      p<0.0001). Finally, the results suggest that plasma levels of PMPs diminish as
      patient experience more episodes of clinical malaria (beta=0.07, p<0.003).
      CONCLUSIONS: Abundant circulating MPs are present during acute P. vivax
      infection, and platelet derived-MPs may play a role on the acute inflammatory
      symptoms of malaria vivax.

PMID- 21080933
TI  - Acoustic cardiac triggering: a practical solution for synchronization and gating
      of cardiovascular magnetic resonance at 7 Tesla.
AB  - BACKGROUND: To demonstrate the applicability of acoustic cardiac triggering (ACT)
      for imaging of the heart at ultrahigh magnetic fields (7.0 T) by comparing
      phonocardiogram, conventional vector electrocardiogram (ECG) and traditional
      pulse oximetry (POX) triggered 2D CINE acquisitions together with (i) a
      qualitative image quality analysis, (ii) an assessment of the left ventricular
      function parameter and (iii) an examination of trigger reliability and trigger
      detection variance derived from the signal waveforms. RESULTS: ECG was
      susceptible to severe distortions at 7.0 T. POX and ACT provided waveforms free
      of interferences from electromagnetic fields or from magneto-hydrodynamic
      effects. Frequent R-wave mis-registration occurred in ECG-triggered acquisitions
      with a failure rate of up to 30% resulting in cardiac motion induced artifacts.
      ACT and POX triggering produced images free of cardiac motion artefacts. ECG
      showed a severe jitter in the R-wave detection. POX also showed a trigger jitter
      of approximately Deltat = 72 ms which is equivalent to two cardiac phases. ACT
      showed a jitter of approximately Deltat = 5 ms only. ECG waveforms revealed a
      standard deviation for the cardiac trigger offset larger than that observed for
      ACT or POX waveforms.Image quality assessment showed that ACT substantially
      improved image quality as compared to ECG (image quality score at end-diastole:
      ECG = 1.7 +/- 0.5, ACT = 2.4 +/- 0.5, p = 0.04) while the comparison between ECG
      vs. POX gated acquisitions showed no significant differences in image quality
      (image quality score: ECG = 1.7 +/- 0.5, POX = 2.0 +/- 0.5, p = 0.34).
      CONCLUSIONS: The applicability of acoustic triggering for cardiac CINE imaging at
      7.0 T was demonstrated. ACT's trigger reliability and fidelity are superior to
      that of ECG and POX. ACT promises to be beneficial for cardiovascular magnetic
      resonance at ultra-high field strengths including 7.0 T.

PMID- 21080935
TI  - Merging transcriptomics and metabolomics--advances in breast cancer profiling.
AB  - BACKGROUND: Combining gene expression microarrays and high resolution magic angle
      spinning magnetic resonance spectroscopy (HR MAS MRS) of the same tissue samples
      enables comparison of the transcriptional and metabolic profiles of breast
      cancer. The aim of this study was to explore the potential of combining these two
      different types of information. METHODS: Breast cancer tissue from 46 patients
      was analyzed by HR MAS MRS followed by gene expression microarrays. Two
      strategies were used to combine the gene expression and metabolic data; first
      using multivariate analyses to identify different groups based on gene expression
      and metabolic data; second correlating levels of specific metabolites to
      transcripts to suggest new hypotheses of connections between metabolite levels
      and the underlying biological processes. A parallel study was designed to address
      experimental issues of combining microarrays and HR MAS MRS. RESULTS: In the
      first strategy, using the microarray data and previously reported molecular
      classification methods, the majority of samples were classified as luminal A.
      Three subgroups of luminal A tumors were identified based on hierarchical
      clustering of the HR MAS MR spectra. The samples in one of the subgroups,
      designated A2, showed significantly lower glucose and higher alanine levels than
      the other luminal A samples, suggesting a higher glycolytic activity in these
      tumors. This group was also enriched for genes annotated with Gene Ontology (GO)
      terms related to cell cycle and DNA repair. In the second strategy, the
      correlations between concentrations of myo-inositol, glycine, taurine,
      glycerophosphocholine, phosphocholine, choline and creatine and all transcripts
      in the filtered microarray data were investigated. GO-terms related to the
      extracellular matrix were enriched among the genes that correlated the most to
      myo-inositol and taurine, while cell cycle related GO-terms were enriched for the
      genes that correlated the most to choline. Additionally, a subset of transcripts
      was identified to have slightly altered expression after HR MAS MRS and was
      therefore removed from all other analyses. CONCLUSIONS: Combining transcriptional
      and metabolic data from the same breast carcinoma sample is feasible and may
      contribute to a more refined subclassification of breast cancers as well as
      reveal relations between metabolic and transcriptional levels. See Commentary:
      http://www.biomedcentral.com/1741-7015/8/73.

PMID- 21080934
TI  - Germline transformation of the stalk-eyed fly, Teleopsis dalmanni.
AB  - BACKGROUND: Stalk-eyed flies of the family Diopsidae have proven to be an
      excellent model organism for studying the evolution of ornamental sexual traits.
      In diopsid flies the eyes and antennae are borne at the end of lateral head
      projections called 'eye-stalks'. Eyespan, the distance between the eyes, and the
      degree of sexual dimorphism in eyespan vary considerably between species and
      several sexually dimorphic species show sexual selection through female mate
      preference for males with exaggerated eyespan. Relatively little is known about
      the molecular genetic basis of intra- or inter-species variation in eyespan, eye
      stalk development or growth regulation in diopsids. Molecular approaches
      including comparative developmental analyses, EST screening and QTL mapping have
      identified potential candidate loci for eyespan regulation in the model species
      Teleopsis dalmanni. Functional analyses of these genes to confirm and fully
      characterise their roles in eye-stalk growth require the development of
      techniques such as germline transformation to manipulate gene activity in vivo.
      RESULTS: We used in vivo excision assays to identify transposon vector systems
      with the activity required to mediate transgenesis in T. dalmanni. Mariner based
      vectors showed no detectable excision while both Minos and piggyBac were active
      in stalk-eyed fly embryos. Germline transformation with an overall efficiency of
      4% was achieved using a Minos based vector and the 3xP3-EGFP marker construct.
      Chromosomal insertion of constructs was confirmed by Southern blot analysis. Both
      autosomal and X-linked inserts were recovered. A homozygous stock, established
      from one of the X-linked inserts, has maintained stable expression for eight
      generations. CONCLUSIONS: We have performed stable germline transformation of a
      stalk-eyed fly, T. dalmanni. This is the first transgenic protocol to be
      developed in an insect species that exhibits an exaggerated male sexual trait.
      Transgenesis will enable the development of a range of techniques for analysing
      gene function in this species and so provide insight into the mechanisms
      underlying the development of a morphological trait subject to sexual selection.
      Our X-linked insertion line will permit the sex of live larvae to be determined.
      This will greatly facilitate the identification of genes which are differentially
      expressed during eye-stalk development in males and females.

PMID- 21080936
TI  - Can metabolomics in addition to genomics add to prognostic and predictive
      information in breast cancer?
AB  - Genomic data from breast cancers provide additional prognostic and predictive
      information that is beginning to be used for patient management. The question
      arises whether additional information derived from other 'omic' approaches such
      as metabolomics can provide additional information. In an article published this
      month in BMC Cancer, Borgan et al. add metabolomic information to genomic
      measures in breast tumours and demonstrate, for the first time, that it may be
      possible to further define subgroups of patients which could be of value
      clinically. See research article: http://www.biomedcentral.com/1471-2407/10/628.

PMID- 21080937
TI  - Investigating the evolution of apoptosis in malaria parasites: the importance of
      ecology.
AB  - Apoptosis is a precisely regulated process of cell death which occurs widely in
      multicellular organisms and is essential for normal development and immune
      defences. In recent years, interest has grown in the occurrence of apoptosis in
      unicellular organisms. In particular, as apoptosis has been reported in a wide
      range of species, including protozoan malaria parasites and trypanosomes, it may
      provide a novel target for intervention. However, it is important to understand
      when and why parasites employ an apoptosis strategy before the likely long- and
      short-term success of such an intervention can be evaluated. The occurrence of
      apoptosis in unicellular parasites provides a challenge for evolutionary theory
      to explain as organisms are expected to have evolved to maximise their own
      proliferation, not death. One possible explanation is that protozoan parasites
      undergo apoptosis in order to gain a group benefit from controlling their density
      as this prevents premature vector mortality. However, experimental manipulations
      to examine the ultimate causes behind apoptosis in parasites are lacking. In this
      review, we focus on malaria parasites to outline how an evolutionary framework
      can help make predictions about the ecological circumstances under which
      apoptosis could evolve. We then highlight the ecological considerations that
      should be taken into account when designing evolutionary experiments involving
      markers of cell death, and we call for collaboration between researchers in
      different fields to identify and develop appropriate markers in reference to
      parasite ecology and to resolve debates on terminology.

PMID- 21080940
TI  - Measuring the health of the Indian elderly: evidence from National Sample Survey
      data.
AB  - BACKGROUND: Comparable health measures across different sets of populations are
      essential for describing the distribution of health outcomes and assessing the
      impact of interventions on these outcomes. Self-reported health (SRH) is a
      commonly used indicator of health in household surveys and has been shown to be
      predictive of future mortality. However, the susceptibility of SRH to influence
      by individuals' expectations complicates its interpretation and undermines its
      usefulness. METHODS: This paper applies the empirical methodology of Lindeboom
      and van Doorslaer (2004) to investigate elderly health in India using data from
      the 52nd round of the National Sample Survey conducted in 1995-96 that includes
      both an SRH variable as well as a range of objective indicators of disability and
      ill health. The empirical testing was conducted on stratified homogeneous groups,
      based on four factors: gender, education, rural-urban residence, and region.
      RESULTS: We find that region generally has a significant impact on how women
      perceive their health. Reporting heterogeneity can arise not only from cut-point
      shifts, but also from differences in health effects by objective health measures.
      In contrast, we find little evidence of reporting heterogeneity due to
      differences in gender or educational status within regions. Rural-urban residence
      does matter in some cases. The findings are robust with different specifications
      of objective health indicators. CONCLUSIONS: Our exercise supports the thesis
      that the region of residence is associated with different cut-points and
      reporting behavior on health surveys. We believe this is the first paper that
      applies the Lindeboom-van Doorslaer methodology to data on the elderly in a
      developing country, showing the feasibility of applying this methodology to data
      from many existing cross-sectional health surveys.

PMID- 21080939
TI  - Sequencing, de novo annotation and analysis of the first Anguilla anguilla
      transcriptome: EeelBase opens new perspectives for the study of the critically
      endangered European eel.
AB  - BACKGROUND: Once highly abundant, the European eel (Anguilla anguilla L.;
      Anguillidae; Teleostei) is considered to be critically endangered and on the
      verge of extinction, as the stock has declined by 90-99% since the 1980s. Yet,
      the species is poorly characterized at molecular level with little sequence
      information available in public databases. RESULTS: The first European eel
      transcriptome was obtained by 454 FLX Titanium sequencing of a normalized cDNA
      library, produced from a pool of 18 glass eels (juveniles) from the French
      Atlantic coast and two sites in the Mediterranean coast. Over 310,000 reads were
      assembled in a total of 19,631 transcribed contigs, with an average length of 531
      nucleotides. Overall 36% of the contigs were annotated to known
      protein/nucleotide sequences and 35 putative miRNA identified. CONCLUSIONS: This
      study represents the first transcriptome analysis for a critically endangered
      species. EeelBase, a dedicated database of annotated transcriptome sequences of
      the European eel is freely available at http://compgen.bio.unipd.it/eeelbase.
      Considering the multiple factors potentially involved in the decline of the
      European eel, including anthropogenic factors such as pollution and human
      introduced diseases, our results will provide a rich source of data to discover
      and identify new genes, characterize gene expression, as well as for
      identification of genetic markers scattered across the genome to be used in
      various applications.

PMID- 21080941
TI  - Fatty acid synthase phosphorylation: a novel therapeutic target in HER2
      overexpressing breast cancer cells.
AB  - INTRODUCTION: The human epidermal growth factor receptor 2 (HER2) is a validated
      therapeutic target in breast cancer. Heterodimerization of HER2 with other HER
      family members results in enhanced tyrosine phosphorylation and activation of
      signal transduction pathways. HER2 overexpression increases the translation of
      fatty acid synthase (FASN), and FASN overexpression markedly increases HER2
      signaling, which results in enhanced cell growth. However, the molecular
      mechanism and regulation of HER2 and FASN interaction are not well defined.
      Lapatinib is a small-molecule tyrosine kinase inhibitor that blocks
      phosphorylation of the epidermal growth factor receptor and HER2 in breast cancer
      cells, resulting in apoptosis. We hypothesized that FASN is directly
      phosphorylated by HER2, resulting in enhanced signaling and tumor progression in
      breast cancer cells. METHODS: Using mass spectrometry, we identified FASN as one
      of the proteins that is dephosphorylated by lapatinib in SKBR3 breast cancer
      cells. Immunofluorescence, immunoprecipitation, Western blotting, a kinase assay,
      a FASN enzymatic activity assay, an invasion assay, a cell viability assay and
      zymography were used to determine the role of FASN phosphorylation in invasion of
      SKBR3 and BT474 cells. The FASN inhibitor C75 and small interfering RNA were used
      to downregulate FASN expression and/or activity. RESULTS: Our data demonstrated
      that FASN is phosphorylated when it is in complex with HER2. FASN phosphorylation
      was induced by heregulin in HER2-overexpressing SKBR3 and BT474 breast cancer
      cells. Heregulin-induced FASN phosphorylation resulted in increased FASN
      enzymatic activity, which was inhibited by lapatinib. The FASN inhibitor C75
      suppressed FASN activity by directly inhibiting HER2 and FASN phosphorylation.
      Blocking FASN phosphorylation and activity by lapatinib or C75 suppressed the
      activity of matrix metallopeptidase 9 and inhibited invasion of SKBR3 and BT474
      cells. CONCLUSIONS: FASN phosphorylation by HER2 plays an important role in
      breast cancer progression and may be a novel therapeutic target in HER2
      overexpressing breast cancer cells.

PMID- 21080942
TI  - Mice lacking the Cbeta subunit of PKA are resistant to angiotensin II-induced
      cardiac hypertrophy and dysfunction.
AB  - BACKGROUND: PKA is a ubiquitous, multi-subunit cellular kinase that regulates a
      number of different physiological responses in response to cAMP, including
      metabolism, cell division, and cardiac function. Numerous studies have implicated
      altered PKA signaling in cardiac dysfunction. Recently, it has been shown that
      mice lacking the catalytic beta subunit of PKA (PKA Cbeta) are protected from age
      related problems such as weight gain and enlarged livers, and we hypothesized
      that these mice might also be resistant to cardiomyopathy. FINDINGS: Angiotensin
      II (ang II) induced hypertension in both PKA Cbeta null mice and their WT
      littermates. However, PKA Cbeta null mice were resistant to a number of ang II
      induced, cardiopathological effects observed in the WT mice, including
      hypertrophy, decreased diastolic performance, and enlarged left atria.
      CONCLUSION: The Cbeta subunit of PKA plays an important role in angiotensin
      induced cardiac dysfunction. The Cbeta null mouse highlights the potential of the
      PKA Cbeta subunit as a pharmaceutical target for hypertrophic cardiac disease.

PMID- 21080943
TI  - Local topographic wetness indices predict household malaria risk better than land
      use and land-cover in the western Kenya highlands.
AB  - BACKGROUND: Identification of high-risk malaria foci can help enhance
      surveillance or control activities in regions where they are most needed.
      Associations between malaria risk and land-use/land-cover are well-recognized,
      but these environmental characteristics are closely interrelated with the land's
      topography (e.g., hills, valleys, elevation), which also influences malaria risk
      strongly. Parsing the individual contributions of land-cover/land-use variables
      to malaria risk requires examining these associations in the context of their
      topographic landscape. This study examined whether environmental factors like
      land-cover, land-use, and urban density improved malaria risk prediction based
      solely on the topographically-determined context, as measured by the topographic
      wetness index. METHODS: The topographic wetness index, an estimate of predicted
      water accumulation in a defined area, was generated from a digital terrain model
      of the landscape surrounding households in two neighbouring western Kenyan
      highland communities. Variables determined to best encompass the variance in this
      topographic wetness surface were calculated at a household level. Land-cover/land
      use information was extracted from a high-resolution satellite image using an
      object-based classification method. Topographic and land-cover variables were
      used individually and in combination to predict household-level malaria in the
      communities through an iterative split-sample model fitting and testing
      procedure. Models with only topographic variables were compared to those with
      additional predictive factors related to land-cover/land-use to investigate
      whether these environmental factors improved prediction of malaria based on the
      shape of the land alone. RESULTS: Variables related to topographic wetness proved
      most useful in predicting the households of individuals contracting malaria in
      this region of rugged terrain. Other variables related to human modification of
      the environment also demonstrated clear associations with household malaria.
      However, these land-cover/land-use variables failed to produce unambiguous
      improvements in statistical predictive models controlling for important
      topographic factors, with none improving prediction of household-level malaria
      more than 75% of the time. CONCLUSIONS: Topographic wetness values in this region
      of highly varied terrain more accurately predicted houses at greater risk of
      malaria than did consideration of land-cover/land-use characteristics. As such,
      those planning control or local elimination strategies in similar highland
      regions may use topographic and geographic characteristics to effectively
      identify high-receptivity regions that may require enhanced vigilance.

PMID- 21080944
TI  - Analysis of the expression pattern of the BCL11B gene and its relatives in
      patients with T-cell acute lymphoblastic leukemia.
AB  - BACKGROUND: In a human T-cell acute lymphoblastic leukemia (T-ALL) cell line
      (Molt-4), siRNA-mediated suppression of BCL11B expression was shown to inhibit
      proliferation and induce apoptosis, functions which may be related to genes
      involved in apoptosis (such as TNFSF10 and BCL2L1) and TGF-beta pathways (such as
      SPP1and CREBBP). METHODS: The expression levels of the above mentioned genes and
      their correlation with the BCL11B gene were analyzed in patients with T-ALL using
      the TaqMan and SYBR Green I real-time polymerase chain reaction technique.
      RESULTS: Expression levels of BCL11B, BCL2L1, and CREBBP mRNA in T-ALL patients
      were significantly higher than those from healthy controls (P<0.05). In T-ALL
      patients, the BCL11B expression level was negatively correlated with the BCL2L1
      expression level (rs=-0.700; P<0.05), and positively correlated with the SPP1
      expression level (rs=0.683; P<0.05). In healthy controls, the BCL11B expression
      level did not correlate with the TNFSF10, BCL2L1, SPP1, or CREBBP expression
      levels. CONCLUSIONS: Over-expression of BCL11B might play a role in anti
      apoptosis in T-ALL cells through up-regulation of its downstream genes BCL2L1 and
      CREBBP.

PMID- 21080938
TI  - Insights into metazoan evolution from Alvinella pompejana cDNAs.
AB  - BACKGROUND: Alvinella pompejana is a representative of Annelids, a key phylum for
      evo-devo studies that is still poorly studied at the sequence level. A. pompejana
      inhabits deep-sea hydrothermal vents and is currently known as one of the most
      thermotolerant Eukaryotes in marine environments, withstanding the largest known
      chemical and thermal ranges (from 5 to 105 degrees C). This tube-dwelling worm
      forms dense colonies on the surface of hydrothermal chimneys and can withstand
      long periods of hypo/anoxia and long phases of exposure to hydrogen sulphides. A.
      pompejana specifically inhabits chimney walls of hydrothermal vents on the East
      Pacific Rise. To survive, Alvinella has developed numerous adaptations at the
      physiological and molecular levels, such as an increase in the thermostability of
      proteins and protein complexes. It represents an outstanding model organism for
      studying adaptation to harsh physicochemical conditions and for isolating stable
      macromolecules resistant to high temperatures. RESULTS: We have constructed four
      full length enriched cDNA libraries to investigate the biology and evolution of
      this intriguing animal. Analysis of more than 75,000 high quality reads led to
      the identification of 15,858 transcripts and 9,221 putative protein sequences.
      Our annotation reveals a good coverage of most animal pathways and networks with
      a prevalence of transcripts involved in oxidative stress resistance,
      detoxification, anti-bacterial defence, and heat shock protection. Alvinella
      proteins seem to show a slow evolutionary rate and a higher similarity with
      proteins from Vertebrates compared to proteins from Arthropods or Nematodes.
      Their composition shows enrichment in positively charged amino acids that might
      contribute to their thermostability. The gene content of Alvinella reveals that
      an important pool of genes previously considered to be specific to Deuterostomes
      were in fact already present in the last common ancestor of the Bilaterian
      animals, but have been secondarily lost in model invertebrates. This pool is
      enriched in glycoproteins that play a key role in intercellular communication,
      hormonal regulation and immunity. CONCLUSIONS: Our study starts to unravel the
      gene content and sequence evolution of a deep-sea annelid, revealing key features
      in eukaryote adaptation to extreme environmental conditions and highlighting the
      proximity of Annelids and Vertebrates.

PMID- 21080945
TI  - Validity and inter-rater reliability of medio-lateral knee motion observed during
      a single-limb mini squat.
AB  - BACKGROUND: Muscle function may influence the risk of knee injury and outcomes
      following injury. Clinical tests, such as a single-limb mini squat, resemble
      conditions of daily life and are easy to administer. Fewer squats per 30 seconds
      indicate poorer function. However, the quality of movement, such as the medio
      lateral knee motion may also be important. The aim was to validate an
      observational clinical test of assessing the medio-lateral knee motion, using a
      three-dimensional (3-D) motion analysis system. In addition, the inter-rater
      reliability was evaluated. METHODS: Twenty-five (17 women) non-injured
      participants (mean age 25.6 years, range 18-37) were included. Visual analysis of
      the medio-lateral knee motion, scored as knee-over-foot or knee-medial-to-foot by
      two raters, and 3-D kinematic data were collected simultaneously during a single
      limb mini squat. Frontal plane 2-D peak tibial, thigh, and knee varus-valgus
      angles, and 3-D peak hip internal-external rotation, and knee varus-valgus angles
      were calculated. RESULTS: Ten subjects were scored as having a knee-medial-to
      foot position and 15 subjects a knee-over-foot position assessed by visual
      inspection. In 2-D, the peak tibial angle (mean 89.0 (SE 0.7) vs mean 86.3 (SE
      0.4) degrees, p = 0.001) and peak thigh angle (mean 77.4 (SE 1.0) vs mean 81.2
      (SE 0.5) degrees, p = 0.001) with respect to the horizontal, indicated that the
      knee was more medially placed than the ankle and thigh, respectively. Thus, the
      knee was in more valgus (mean 11.6 (SE 1.5) vs 5.0 (SE 0.8) degrees, p < 0.001)
      in subjects with the knee-medial-to-foot than in those with a knee-over-foot
      position. In 3-D, the hip was more internally rotated in those with a knee-medial
      to-foot than in those with a knee-over-foot position (mean 10.6 (SE 2.1) vs 4.8
      (SE 1.8) degrees, p = 0.049), but there was no difference in knee valgus (mean
      6.1 (SE 1.8) vs mean 5.0 (SE 1.2) degrees, p = 0.589). The kappa value and
      percent agreement, respectively, was >0.90 and 96 between raters. CONCLUSIONS:
      Medio-lateral motion of the knee can reliably be assessed during a single-leg
      mini-squat. The test is valid in 2-D, while the actual movement, in 3-D, is
      mainly exhibited as increased internal hip rotation. The single-limb mini squat
      is feasible and easy to administer in the clinical setting and in research to
      address lower extremity movement quality.

PMID- 21080947
TI  - PSAPP mice exhibit regionally selective reductions in gliosis and plaque
      deposition in response to S100B ablation.
AB  - BACKGROUND: Numerous studies have reported that increased expression of S100B, an
      intracellular Ca2+ receptor protein and secreted neuropeptide, exacerbates
      Alzheimer's disease (AD) pathology. However, the ability of S100B inhibitors to
      prevent/reverse AD histopathology remains controversial. This study examines the
      effect of S100B ablation on in vivo plaque load, gliosis and dystrophic neurons.
      METHODS: Because S100B-specific inhibitors are not available, genetic ablation
      was used to inhibit S100B function in the PSAPP AD mouse model. The PSAPP/S100B-/
      line was generated by crossing PSAPP double transgenic males with S100B-/-
      females and maintained as PSAPP/S100B+/- crosses. Congo red staining was used to
      quantify plaque load, plaque number and plaque size in 6 month old PSAPP and
      PSAPP/S100B-/- littermates. The microglial marker Iba1 and astrocytic marker
      glial fibrillary acidic protein (GFAP) were used to quantify gliosis. Dystrophic
      neurons were detected with the phospho-tau antibody AT8. S100B
      immunohistochemistry was used to assess the spatial distribution of S100B in the
      PSAPP line. RESULTS: PSAPP/S100B-/- mice exhibited a regionally selective
      decrease in cortical but not hippocampal plaque load when compared to PSAPP
      littermates. This regionally selective reduction in plaque load was accompanied
      by decreases in plaque number, GFAP-positive astrocytes, Iba1-positive microglia
      and phospho-tau positive dystrophic neurons. These effects were not attributable
      to regional variability in the distribution of S100B. Hippocampal and cortical
      S100B immunoreactivity in PSAPP mice was associated with plaques and co-localized
      with astrocytes and microglia. CONCLUSIONS: Collectively, these data support
      S100B inhibition as a novel strategy for reducing cortical plaque load, gliosis
      and neuronal dysfunction in AD and suggest that both extracellular as well as
      intracellular S100B contribute to AD histopathology.

PMID- 21080949
TI  - Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and
      osteoarthritis: results of a meta-analysis.
AB  - BACKGROUND: The objective of this study was to examine the relationship between
      common genetic variation of the ESR2 gene and osteoarthritis. METHODS: In the
      discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs)
      were genotyped and tested for association with hip (284 cases, 2772 controls),
      knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an
      additive model. In the replication stage one SNP (rs1256031) was tested in an
      additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699
      controls respectively. Fixed- and random-effects meta-analyses were performed
      over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases
      and approximately 6000 controls. RESULTS: The C allele of rs1256031 was
      associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I
      (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee-
      and hand OA did not give additional information. With the replication studies,
      the meta-analysis did not show a significant effect of this SNP on hip OA in the
      total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according
      to gender did not change the results. In this study, we had 80% power to detect
      an odds ratio of at least 1.14 for hip OA (alpha = 0.05). CONCLUSION: This study
      showed that common genetic variation in the ESR2 gene is not likely to influence
      the risk of osteoarthritis with effects smaller than a 13% increase.

PMID- 21080948
TI  - Mining the bitter melon (momordica charantia l.) seed transcriptome by 454
      analysis of non-normalized and normalized cDNA populations for conjugated fatty
      acid metabolism-related genes.
AB  - BACKGROUND: Seeds of Momordica charantia (bitter melon) produce high levels of
      eleostearic acid, an unusual conjugated fatty acid with industrial value. Deep
      sequencing of non-normalized and normalized cDNAs from developing bitter melon
      seeds was conducted to uncover key genes required for biotechnological transfer
      of conjugated fatty acid production to existing oilseed crops. It is expected
      that these studies will also provide basic information regarding the metabolism
      of other high-value novel fatty acids. RESULTS: Deep sequencing using 454
      technology with non-normalized and normalized cDNA libraries prepared from bitter
      melon seeds at 18 DAP resulted in the identification of transcripts for the vast
      majority of known genes involved in fatty acid and triacylglycerol biosynthesis.
      The non-normalized library provided a transcriptome profile of the early stage in
      seed development that highlighted the abundance of transcripts for genes encoding
      seed storage proteins as well as for a number of genes for lipid metabolism
      associated polypeptides, including Delta12 oleic acid desaturases and fatty acid
      conjugases, class 3 lipases, acyl-carrier protein, and acyl-CoA binding protein.
      Normalization of cDNA by use of a duplex-specific nuclease method not only
      increased the overall discovery of genes from developing bitter melon seeds, but
      also resulted in the identification of 345 contigs with homology to 189 known
      lipid genes in Arabidopsis. These included candidate genes for eleostearic acid
      metabolism such as diacylglycerol acyltransferase 1 and 2, and a
      phospholipid:diacylglycerol acyltransferase 1-related enzyme. Transcripts were
      also identified for a novel FAD2 gene encoding a functional Delta12 oleic acid
      desaturase with potential implications for eleostearic acid biosynthesis.
      CONCLUSIONS: 454 deep sequencing, particularly with normalized cDNA populations,
      was an effective method for mining of genes associated with eleostearic acid
      metabolism in developing bitter melon seeds. The transcriptomic data presented
      provide a resource for the study of novel fatty acid metabolism and for the
      biotechnological production of conjugated fatty acids and possibly other novel
      fatty acids in established oilseed crops.

PMID- 21080951
TI  - Carcinogen metabolism, cigarette smoking, and breast cancer risk: a Bayes model
      averaging approach.
AB  - BACKGROUND: Standard logistic regression with or without stepwise selection has
      the disadvantage of not incorporating model uncertainty and the dependency of
      estimates on the underlying model into the final inference. We explore the use of
      a Bayes Model Averaging approach as an alternative to analyze the influence of
      genetic variants, environmental effects and their interactions on disease.
      METHODS: Logistic regression with and without stepwise selection and Bayes Model
      Averaging were applied to a population-based case-control study exploring the
      association of genetic variants in tobacco smoke-related carcinogen pathways with
      breast cancer. RESULTS: Both regression and Bayes Model Averaging highlighted a
      significant effect of NAT1*10 on breast cancer, while regression analysis also
      suggested a significant effect for packyears and for the interaction of packyears
      and NAT2. CONCLUSIONS: Bayes Model Averaging allows incorporation of model
      uncertainty, helps reduce dimensionality and avoids the problem of multiple
      comparisons. It can be used to incorporate biological information, such as
      pathway data, into the analysis. As with all Bayesian analysis methods, careful
      consideration must be given to prior specification.

PMID- 21080950
TI  - Bone morphogenetic protein (BMP)-7 expression is decreased in human hypertensive
      nephrosclerosis.
AB  - BACKGROUND: Bone Morphogenetic Protein (BMP)-7 is protective in different animal
      models of acute and chronic kidney disease. Its role in human kidneys, and in
      particular hypertensive nephrosclerosis, has thus far not been described.
      METHODS: BMP-7 mRNA was quantified using real-time PCR and localised by
      immunostaining in tissue samples from normal and nephrosclerotic human kidneys.
      The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan
      on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was
      quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7
      were evaluated by testing its influence on TGF-beta induced epithelial-to
      mesenchymal transition (EMT), expression of TGF-beta receptor type I (TGF-betaRI)
      and phosphorylated Smad 2 (pSmad 2) as well as on TNF-alpha induced apoptosis of
      proximal tubular cells. RESULTS: BMP-7 was predominantly found in the epithelia
      of the distal tubule and the collecting duct and was less abundant in proximal
      tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as
      demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells
      led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially
      ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP
      7 (100 ng/ml) were able to reverse TNF-alpha-induced apoptosis and TGF-beta
      induced EMT in human proximal tubule cells possibly due to a decreased expression
      of TGF-betaRI. In addition, BMP-7 was able to reverse TGF-beta-induced
      phosphorylation of Smad 2. CONCLUSIONS: The findings suggest a protective role
      for BMP-7 by counteracting the TGF-beta and TNF-alpha-induced negative effects.
      The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may
      imply loss of protection and regenerative potential necessary to counter the
      disease.

PMID- 21080952
TI  - Patterns of neural differentiation in melanomas.
AB  - BACKGROUND: Melanomas, highly malignant tumors arise from the melanocytes which
      originate as multipotent neural crest cells during neural tube genesis. The
      purpose of this study is to assess the pattern of neural differentiation in
      relation to angiogenesis in VGP melanomas using the tumor as a three dimensional
      system. METHODS: Tumor-vascular complexes [TVC] are formed at the tumor-stroma
      interphase, by tumor cells ensheathing angiogenic vessels to proliferate into a
      mantle of 5 to 6 layers [L1 to L5] forming a perivascular mantle zone [PMZ]. The
      pattern of neural differentiation is assessed by immunopositivity for HMB45,
      GFAP, NFP and synaptophysin has been compared in: [a] the general tumor [b] tumor
      vascular complexes and [c] perimantle zone [PC] on serial frozen and paraffin
      sections. STATISTICAL ANALYSIS: ANOVA: Kruskal-Wallis One Way Analysis of
      Variance; All Pairwise Multiple Comparison Procedures [Tukey Test]. RESULTS: The
      cells abutting on the basement membrane acquire GFAP positivity and extend
      processes. New layers of tumor cells show a transition between L2 to L3 followed
      by NFP and Syn positivity in L4&L5. The level of GFAP+vity in L1&L2 directly
      proportionate to the percentage of NFP/Syn+vity in L4&L5, on comparing pigmented
      PMZ with poorly pigmented PMZ. Tumor cells in the perimantle zone show high NFP
      [65%] and Syn [35.4%] positivity with very low GFAP [6.9%] correlating with the
      positivity in the outer layers. DISCUSSION: From this study it is seen that
      melanoma cells revert to the embryonic pattern of differentiation, with radial
      glial like cells [GFAP+ve] which further differentiate into neuronal positive
      cells [NFP&Syn+ve] during angiogenic tumor-vascular interaction, as seen during
      neurogenesis, to populate the tumor substance.

PMID- 21080954
TI  - Motivation and job satisfaction among medical and nursing staff in a Cyprus
      public general hospital.
AB  - BACKGROUND: The objective of this study was to investigate how medical and
      nursing staff of the Nicosia General Hospital is affected by specific motivation
      factors, and the association between job satisfaction and motivation.
      Furthermore, to determine the motivational drive of socio-demographic and job
      related factors in terms of improving work performance. METHODS: A previously
      developed and validated instrument addressing four work-related motivators (job
      attributes, remuneration, co-workers and achievements) was used. Two categories
      of health care professionals, medical doctors and dentists (N = 67) and nurses (N
      = 219) participated and motivation and job satisfaction was compared across socio
      demographic and occupational variables. RESULTS: The survey revealed that
      achievements was ranked first among the four main motivators, followed by
      remuneration, co-workers and job attributes. The factor remuneration revealed
      statistically significant differences according to gender, and hospital sector,
      with female doctors and nurses and accident and emergency (A+E) outpatient
      doctors reporting greater mean scores (p < 0.005). The medical staff showed
      statistically significantly lower job satisfaction compared to the nursing staff.
      Surgical sector nurses and those >55 years of age reported higher job
      satisfaction when compared to the other groups. CONCLUSIONS: The results are in
      agreement with the literature which focuses attention to management approaches
      employing both monetary and non-monetary incentives to motivate health care
      professionals. Health care professionals tend to be motivated more by intrinsic
      factors, implying that this should be a target for effective employee motivation.
      Strategies based on the survey's results to enhance employee motivation are
      suggested.

PMID- 21080946
TI  - Comparative physical maps derived from BAC end sequences of tilapia (Oreochromis
      niloticus).
AB  - BACKGROUND: The Nile tilapia is the second most important fish in aquaculture. It
      is an excellent laboratory model, and is closely related to the African lake
      cichlids famous for their rapid rates of speciation. A suite of genomic resources
      has been developed for this species, including genetic maps and ESTs. Here we
      analyze BAC end-sequences to develop comparative physical maps, and estimate the
      number of genome rearrangements, between tilapia and other model fish species.
      RESULTS: We obtained sequence from one or both ends of 106,259 tilapia BACs.
      BLAST analysis against the genome assemblies of stickleback, medaka and
      pufferfish allowed identification of homologies for approximately 25,000 BACs for
      each species. We calculate that rearrangement breakpoints between tilapia and
      these species occur about every 3 Mb across the genome. Analysis of 35,000 clones
      previously assembled into contigs by restriction fingerprints allowed
      identification of longer-range syntenies. CONCLUSIONS: Our data suggest that
      chromosomal evolution in recent teleosts is dominated by alternate loss of gene
      duplicates, and by intra-chromosomal rearrangements (~one per million years).
      These physical maps are a useful resource for comparative positional cloning of
      traits in cichlid fishes. The paired BAC end sequences from these clones will be
      an important resource for scaffolding forthcoming shotgun sequence assemblies of
      the tilapia genome.

PMID- 21080953
TI  - A single mutation results in diploid gamete formation and parthenogenesis in a
      Drosophila yemanuclein-alpha meiosis I defective mutant.
AB  - BACKGROUND: Sexual reproduction relies on two key events: formation of cells with
      a haploid genome (the gametes) and restoration of diploidy after fertilization.
      Therefore the underlying mechanisms must have been evolutionary linked and there
      is a need for evidence that could support such a model. RESULTS: We describe the
      identification and the characterization of yem1, the first yem-alpha mutant
      allele (V478E), which to some extent affects diploidy reduction and its
      restoration. Yem-alpha is a member of the Ubinuclein/HPC2 family of proteins that
      have recently been implicated in playing roles in chromatin remodeling in concert
      with HIRA histone chaperone. The yem1 mutant females exhibited disrupted
      chromosome behavior in the first meiotic division and produced very low numbers
      of viable progeny. Unexpectedly these progeny did not display paternal chromosome
      markers, suggesting that they developed from diploid gametes that underwent
      gynogenesis, a form of parthenogenesis that requires fertilization. CONCLUSIONS:
      We focus here on the analysis of the meiotic defects exhibited by yem1 oocytes
      that could account for the formation of diploid gametes. Our results suggest that
      yem1 affects chromosome segregation presumably by affecting kinetochores function
      in the first meiotic division. This work paves the way to further investigations
      on the evolution of the mechanisms that support sexual reproduction.

PMID- 21080956
TI  - A secreted serine protease of Paracoccidioides brasiliensis and its interactions
      with fungal proteins.
AB  - BACKGROUND: Paracoccidioides brasiliensis is a thermodimorphic fungus, the
      causative agent of paracoccidioidomycosis (PCM). Serine proteases are widely
      distributed and this class of peptidase has been related to pathogenesis and
      nitrogen starvation in pathogenic fungi. RESULTS: A cDNA (Pbsp) encoding a
      secreted serine protease (PbSP), was isolated from a cDNA library constructed
      with RNAs of fungal yeast cells recovered from liver of infected mice.
      Recombinant PbSP was produced in Escherichia coli, and used to develop polyclonal
      antibodies that were able to detect a 66 kDa protein in the P. brasiliensis
      proteome. In vitro deglycosylation assays with endoglycosidase H demonstrated
      that PbSP is a N-glycosylated molecule. The Pbsp transcript and the protein were
      induced during nitrogen starvation. The Pbsp transcript was also induced in yeast
      cells infecting murine macrophages. Interactions of PbSP with P. brasiliensis
      proteins were evaluated by two-hybrid assay in the yeast Saccharomyces
      cerevisiae. PbSP interacts with a peptidyl prolyl cis-trans isomerase, calnexin,
      HSP70 and a cell wall protein PWP2. CONCLUSIONS: A secreted subtilisin induced
      during nitrogen starvation was characterized indicating the possible role of this
      protein in the nitrogen acquisition. PbSP interactions with other P. brasiliensis
      proteins were reported. Proteins interacting with PbSP are related to folding
      process, protein trafficking and cytoskeleton reorganization.

PMID- 21080955
TI  - Loss of heterozygosity and SOSTDC1 in adult and pediatric renal tumors.
AB  - BACKGROUND: Deletions within the short arm of chromosome 7 are observed in
      approximately 25% of adult and 10% of Wilms pediatric renal tumors. Within Wilms
      tumors, the region of interest has been delineated to a 2-Mb minimal region that
      includes ten known genes. Two of these ten candidate genes, SOSTDC1 and MEOX2,
      are particularly relevant to tumor development and maintenance. This finding,
      coupled with evidence that SOSTDC1 is frequently downregulated in adult renal
      cancer and regulates both Wingless-Int (Wnt)- and bone morphogenetic protein
      (BMP)-induced signaling, points to a role for SOSTDC1 as a potential tumor
      suppressor. METHODS: To investigate this hypothesis, we interrogated the Oncomine
      database to examine the SOSTDC1 levels in adult renal clear cell tumors and
      pediatric Wilms tumors. We then performed single nucleotide polymorphism (SNP)
      and sequencing analyses of SOSTDC1 in 25 pediatric and 36 adult renal tumors.
      Immunohistochemical staining of patient samples was utilized to examine the
      impact of SOSTDC1 genetic aberrations on SOSTDC1 protein levels and signaling.
      RESULTS: Within the Oncomine database, we found that SOSTDC1 levels were reduced
      in adult renal clear cell tumors and pediatric Wilms tumors. Through SNP and
      sequencing analyses of 25 Wilms tumors, we identified four with loss of
      heterozygosity (LOH) at 7p and three that affected SOSTDC1. Of 36 adult renal
      cancers, we found five with LOH at 7p, two of which affected SOSTDC1.
      Immunohistochemical analysis of SOSTDC1 protein levels within these tumors did
      not reveal a relationship between these instances of SOSTDC1 LOH and SOSTDC1
      protein levels. Moreover, we could not discern any impact of these genetic
      alterations on Wnt signaling as measured by altered beta-catenin levels or
      localization. CONCLUSIONS: This study shows that genetic aberrations near SOSTDC1
      are not uncommon in renal cancer, and occur in adult as well as pediatric renal
      tumors. These observations of SOSTDC1 LOH, however, did not correspond with
      changes in SOSTDC1 protein levels or signaling regulation. Although our
      conclusions are limited by sample size, we suggest that an alternative mechanism
      such as epigenetic silencing of SOSTDC1 may be a key contributor to the reduced
      SOSTDC1 mRNA and protein levels observed in renal cancer.

PMID- 21080957
TI  - Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac
      function, cardiac remodeling, and survival in rats with chronic heart failure.
AB  - BACKGROUND: Accumulating evidence suggests glucagon-like peptide-1 (GLP-1) exerts
      cardioprotective effects in animal models of myocardial infarction (MI). We
      hypothesized that chronic treatment with GLP-1 or the exenatide analog AC3174
      would improve cardiac function, cardiac remodeling, insulin sensitivity, and
      exercise capacity (EC) in rats with MI-induced chronic heart failure (CHF) caused
      by coronary artery ligation. METHODS: Two weeks post-MI, male Sprague-Dawley rats
      were treated with GLP-1 (2.5 or 25 pmol/kg/min), AC3174 (1.7 or 5 pmol/kg/min) or
      vehicle via subcutaneous infusion for 11 weeks. Cardiac function and morphology
      were assessed by echocardiography during treatment. Metabolic, hemodynamic,
      exercise-capacity, and body composition measurements were made at study end.
      RESULTS: Compared with vehicle-treated rats with CHF, GLP-1 or AC3174
      significantly improved cardiac function, including left ventricular (LV) ejection
      fraction, and end diastolic pressure. Cardiac dimensions also improved as
      evidenced by reduced LV end diastolic and systolic volumes and reduced left
      atrial volume. Vehicle-treated CHF rats exhibited fasting hyperglycemia and
      hyperinsulinemia. In contrast, GLP-1 or AC3174 normalized fasting plasma insulin
      and glucose levels. GLP-1 or AC3174 also significantly reduced body fat and fluid
      mass and improved exercise capacity and respiratory efficiency. Four of 16
      vehicle control CHF rats died during the study compared with 1 of 44 rats treated
      with GLP-1 or AC3174. The cellular mechanism by which GLP-1 or AC3174 exert
      cardioprotective effects appears unrelated to changes in GLUT1 or GLUT4
      translocation or expression. CONCLUSIONS: Chronic treatment with either GLP-1 or
      AC3174 showed promising cardioprotective effects in a rat model of CHF. Hence,
      GLP-1 receptor agonists may represent a novel approach for the treatment of
      patients with CHF or cardiovascular disease associated with type 2 diabetes.

PMID- 21080959
TI  - Antiviral activity of Engystol(r) and Gripp-Heel(r): an in-vitro assessment.
AB  - BACKGROUND: Infections with respiratory viruses can activate the innate immune
      response - an important host defence mechanism in the early stage of viral
      infection. Interferon (IFN) release, triggered by virus infection, is an
      important factor in establishing an antiviral state, where IFN activation occurs
      prior to the onset of the adaptive immune response.The two ultra-low-dose
      combination medications, Engystol(r) and Gripp-Heel(r), have documented efficacy
      for the treatment of the respiratory infections. However, the underlying
      antiviral mechanisms remain elusive. METHODS: It was the goal to investigate
      whether Engystol(r) and Gripp-Heel(r) display antiviral activity in a
      prophylactic treatment protocol (2, 24 and 48 h pre-incubation) using a plaque
      reduction assay and whether the medications affect the release of type 1 IFN in
      virus-susceptible cell lines and human peripheral blood mononuclear cells
      (PBMCs). RESULTS: Both medications demonstrate prophylactic effect against viral
      respiratory virus replication. However, when the incubation was continued for up
      to 5 days, both medications exhibited a pronounced antiviral effect which was
      dependent on the pre-incubation time. Moreover, in co-stimulated HeLa cells as
      well as in activated PBMCs Gripp-Heel(r) and Engystol(r) demonstrated an
      increased type 1 IFN production. CONCLUSIONS: Engystol(r) and Gripp-Heel(r)
      inhibited the replication of a variety of respiratory viruses. Additionally, we
      showed that pre-incubation affects the magnitude of the inhibitory effect
      differently for the various tested viruses. Both medications stimulate type 1 IFN
      release in different cell systems which suggests that their antiviral activity
      may be mediated possibly via modulation of the antiviral type 1 IFN host
      response.

PMID- 21080958
TI  - Identification of Lactobacillus plantarum genes modulating the cytokine response
      of human peripheral blood mononuclear cells.
AB  - BACKGROUND: Modulation of the immune system is one of the most plausible
      mechanisms underlying the beneficial effects of probiotic bacteria on human
      health. Presently, the specific probiotic cell products responsible for
      immunomodulation are largely unknown. In this study, the genetic and phenotypic
      diversity of strains of the Lactobacillus plantarum species were investigated to
      identify genes of L. plantarum with the potential to influence the amounts of
      cytokines interleukin 10 (IL-10) and IL-12 and the ratio of IL-10/IL-12 produced
      by peripheral blood mononuclear cells (PBMCs). RESULTS: A total of 42
      Lactobacillus plantarum strains isolated from diverse environmental and human
      sources were evaluated for their capacity to stimulate cytokine production in
      PBMCs. The L. plantarum strains induced the secretion of the anti-inflammatory
      cytokine IL-10 over an average 14-fold range and secretion of the pro
      inflammatory cytokine IL-12 over an average 16-fold range. Comparisons of the
      strain-specific cytokine responses of PBMCs to comparative genome hybridization
      profiles obtained with L. plantarum WCFS1 DNA microarrays (also termed gene-trait
      matching) resulted in the identification of 6 candidate genetic loci with
      immunomodulatory capacities. These loci included genes encoding an N-acetyl
      glucosamine/galactosamine phosphotransferase system, the LamBDCA quorum sensing
      system, and components of the plantaricin (bacteriocin) biosynthesis and
      transport pathway. Deletion of these genes in L. plantarum WCFS1 resulted in
      growth phase-dependent changes in the PBMC IL-10 and IL-12 cytokine profiles
      compared with wild-type cells. CONCLUSIONS: The altered PBMC cytokine profiles
      obtained with the L. plantarum WCFS1 mutants were in good agreement with the
      predictions made by gene-trait matching for the 42 L. plantarum strains. This
      study therefore resulted in the identification of genes present in certain
      strains of L. plantarum which might be responsible for the stimulation of anti-
      or pro-inflammatory immune responses in the gut.

PMID- 21080960
TI  - Health status in routine clinical practice: validity of the clinical COPD
      questionnaire at the individual patient level.
AB  - BACKGROUND: There is a growing interest to use health status or disease control
      questionnaires in routine clinical practice. However, the validity of most
      questionnaires is established using techniques developed for group level
      validation. This study examines a new method, using patient interviews, to
      validate a short health status questionnaire, the Clinical COPD Questionnaire
      (CCQ), at the individual patient level. METHODS: Patients with COPD who visited
      an outpatient clinic completed the CCQ before the consultation, and the
      specialist physician completed it after the consultation. After the consultation
      all patients had a semi-structured in-depth interview. The patients' CCQ scores
      were compared with those of the treating clinician, and with mean scores from 5
      clinicians from a pool of 20 who scored the CCQ after reading the transcript of
      the in-depth interviews only. Agreement was assessed using Lin's concordance
      correlation coefficient (CCC), and Blant and Altman plots. Interviews with
      patients with low agreement were reviewed for possible explanations. RESULTS: A
      total of 44 COPD patients (32 male, mean age 66 years, FEV1 45% of predicted)
      participated. Agreement between the patients' CCQ scores and those of the
      treating clinicians (CCC = 0.87) and the mean score of the reviewing clinicians
      (CCC = 0.86) was very high. No systematic error was detected. No explanation for
      individuals with low agreement was found. CONCLUSION: The validity of the CCQ on
      the individual patient level, as assessed by these methods, is good. Individual
      health status assessment with the CCQ is therefore sufficiently accurate to be
      used in routine clinical practice.

PMID- 21080961
TI  - Methods for genetic manipulation of Burkholderia gladioli pathovar cocovenenans.
AB  - BACKGROUND: Burkholderia gladioli pathovar cocovenenans (BGC) is responsible for
      sporadic food-poisoning outbreaks with high morbidity and mortality in Asian
      countries. Little is known about the regulation of virulence factor and toxin
      production in BGC, and studies in this bacterium have been hampered by lack of
      genetic tools. FINDINGS: Establishment of a comprehensive antibiotic
      susceptibility profile showed that BGC strain ATCC33664 is susceptible to a
      number of antibiotics including aminoglycosides, carbapenems, fluoroquinolones,
      tetracyclines and trimethoprim. In this study, we established that gentamicin,
      kanamycin and trimethoprim are good selection markers for use in BGC. Using a 10
      min method for preparation of electrocompetent cells, the bacterium could be
      transformed by electroporation at high frequencies with replicative plasmids
      containing the pRO1600-derived origin of replication. These plasmids exhibited a
      copy number of > 100 in BGC. When co-conjugated with a transposase expressing
      helper plasmid, mini-Tn7 vectors inserted site- and orientation-specifically at a
      single glmS-associated insertion site in the BGC genome. Lastly, a Himar1
      transposon was used for random transposon mutagenesis of BGC. CONCLUSIONS: A
      series of genetic tools previously developed for other Gram-negative bacteria was
      adapted for use in BGC. These tools now facilitate genetic studies of this
      pathogen and allow establishment of toxin biosynthetic pathways and their genetic
      regulation.

PMID- 21080962
TI  - Antitumor activity of colloidal silver on MCF-7 human breast cancer cells.
AB  - BACKGROUND: Colloidal silver has been used as an antimicrobial and disinfectant
      agent. However, there is scarce information on its antitumor potential. The aim
      of this study was to determine if colloidal silver had cytotoxic effects on MCF-7
      breast cancer cells and its mechanism of cell death. METHODS: MCF-7 breast cancer
      cells were treated with colloidal silver (ranged from 1.75 to 17.5 ng/mL) for 5 h
      at 37 degrees C and 5% CO2 atmosphere. Cell Viability was evaluated by trypan
      blue exclusion method and the mechanism of cell death through detection of mono
      oligonucleosomes using an ELISA kit and TUNEL assay. The production of NO, LDH,
      and Gpx, SOD, CAT, and Total antioxidant activities were evaluated by
      colorimetric assays. RESULTS: Colloidal silver had dose-dependent cytotoxic
      effect in MCF-7 breast cancer cells through induction of apoptosis, shown an LD50
      (3.5 ng/mL) and LD100 (14 ng/mL) (*P < 0.05), significantly decreased LDH (*P <
      0.05) and significantly increased SOD (*P < 0.05) activities. However, the NO
      production, and Gpx, CAT, and Total antioxidant activities were not affected in
      MCF-7 breast cancer cells. PBMC were not altered by colloidal silver.
      CONCLUSIONS: The present results showed that colloidal silver might be a
      potential alternative agent for human breast cancer therapy.

PMID- 21080963
TI  - A sequence-dependent exonuclease activity from Tetrahymena thermophila.
AB  - BACKGROUND: Telomere function requires a highly conserved G rich 3'- overhang.
      This structure is formed by 5'-resection of the C-rich telomere strand. However,
      while many nucleases have been suggested to play a role in processing, it is not
      yet clear which nucleases carry out this 5'-resection. RESULTS: We used
      biochemical purification to identify a sequence-dependent exonuclease activity in
      Tetrahymena thermophila cell extracts. The nuclease activity showed specificity
      for 5'-ends containing AA or AC sequences, unlike Exo1, which showed sequence
      independent cleavage. The Tetrahymena nuclease was active on both phosphorylated
      and unphosphorylated substrates whereas Exo1 requires a 5'-phosphate for
      cleavage. CONCLUSIONS: The specificities of the enzyme indicate that this novel
      Tetrahymena exonuclease is distinct from Exo1 and has properties required for 3'
      overhang formations at telomeres.

PMID- 21080965
TI  - Empirical bayes analysis of sequencing-based transcriptional profiling without
      replicates.
AB  - BACKGROUND: Recent technological advancements have made high throughput
      sequencing an increasingly popular approach for transcriptome analysis.
      Advantages of sequencing-based transcriptional profiling over microarrays have
      been reported, including lower technical variability. However, advances in
      technology do not remove biological variation between replicates and this
      variation is often neglected in many analyses. RESULTS: We propose an empirical
      Bayes method, titled Analysis of Sequence Counts (ASC), to detect differential
      expression based on sequencing technology. ASC borrows information across
      sequences to establish prior distribution of sample variation, so that biological
      variation can be accounted for even when replicates are not available. Compared
      to current approaches that simply tests for equality of proportions in two
      samples, ASC is less biased towards highly expressed sequences and can identify
      more genes with a greater log fold change at lower overall abundance.
      CONCLUSIONS: ASC unifies the biological and statistical significance of
      differential expression by estimating the posterior mean of log fold change and
      estimating false discovery rates based on the posterior mean. The implementation
      in R is available at http://www.stat.brown.edu/Zwu/research.aspx.

PMID- 21080964
TI  - Analyses of genome architecture and gene expression reveal novel candidate
      virulence factors in the secretome of Phytophthora infestans.
AB  - BACKGROUND: Phytophthora infestans is the most devastating pathogen of potato and
      a model organism for the oomycetes. It exhibits high evolutionary potential and
      rapidly adapts to host plants. The P. infestans genome experienced a repeat
      driven expansion relative to the genomes of Phytophthora sojae and Phytophthora
      ramorum and shows a discontinuous distribution of gene density. Effector genes,
      such as members of the RXLR and Crinkler (CRN) families, localize to expanded,
      repeat-rich and gene-sparse regions of the genome. This distinct genomic
      environment is thought to contribute to genome plasticity and host adaptation.
      RESULTS: We used in silico approaches to predict and describe the repertoire of
      P. infestans secreted proteins (the secretome). We defined the "plastic
      secretome" as a subset of the genome that (i) encodes predicted secreted
      proteins, (ii) is excluded from genome segments orthologous to the P. sojae and
      P. ramorum genomes and (iii) is encoded by genes residing in gene sparse regions
      of P. infestans genome. Although including only ~3% of P. infestans genes, the
      plastic secretome contains ~62% of known effector genes and shows >2 fold
      enrichment in genes induced in planta. We highlight 19 plastic secretome genes
      induced in planta but distinct from previously described effectors. This list
      includes a trypsin-like serine protease, secreted oxidoreductases, small cysteine
      rich proteins and repeat containing proteins that we propose to be novel
      candidate virulence factors. CONCLUSIONS: This work revealed a remarkably diverse
      plastic secretome. It illustrates the value of combining genome architecture with
      comparative genomics to identify novel candidate virulence factors from pathogen
      genomes.

PMID- 21080966
TI  - Human papillomavirus-16 presence and physical status in lung carcinomas from
      Asia.
AB  - BACKGROUND: Although human papillomavirus (HPV) genome has been detected in lung
      cancer, its prevalence is highly variable around the world. Higher frequencies
      have been reported in far-east Asian countries, when compared with European
      countries. The present study analysed the HPV-16 presence in 60 lung carcinomas
      from the Asian countries China, Pakistan and Papua New Guinea. RESULTS: HPV-16
      was present in 8/59 (13%) samples. According to histological type, HPV-16 was
      detected in 8/18 (44%) squamous cell carcinomas (SQCs), which were mainly from
      Pakistan; 0/38 (0%) adenocarcinomas (ACs), which were mainly from China; and in
      0/4 (0%) small cell carcinomas (SCLCs). The observed histological difference was
      statistically significant (p < 0.001). HPV-16 viral load was also determined
      using real-time polymerase chain reaction (qRT-PCR); it ranged between 411 to
      2345 copies/100 ng of genomic DNA. HPV-16 genome was found integrated into the
      host genome in every HPV-16 positive carcinoma. CONCLUSION: These results support
      the notion that HPV-16 infection is highly associated with SQCs in Pakistan. Our
      results show a frequent HPV-16 integration in SQCs, although the low viral load
      casts doubt respect a direct etiological role of HPV in lung carcinomas from
      Asia. Additional HPV-16 characterization is necessary to establish a direct or
      indirect etiological role of HPV in this malignancy.

PMID- 21080968
TI  - Modelling knowlesi malaria transmission in humans: vector preference and host
      competence.
AB  - BACKGROUND: Plasmodium knowlesi, a malaria species that normally infects long
      tailed macaques, was recently found to be prevalent in humans in Southeast Asia.
      While human host competency has been demonstrated experimentally, the extent to
      which the parasite can be transmitted from human back to mosquito vector in
      nature is unclear. METHODS: Using a mathematical model, the influence of human
      host competency on disease transmission is assessed. Adapting a standard model
      for vector-borne disease transmission and using an evolutionary invasion
      analysis, the paper explores how differential host competency between humans and
      macaques can facilitate the epidemiological processes of P. knowlesi infection
      between different hosts. RESULTS: Following current understanding of the
      evolutionary route of other human malaria vectors and parasites, an increasing
      human population in knowlesi malaria endemic regions will select for a more
      anthropophilic vector as well as a parasite that preferentially transmits between
      humans. Applying these adaptations, evolutionary invasion analysis yields
      threshold conditions under which this macaque disease may become a significant
      public health issue. CONCLUSIONS: These threshold conditions are discussed in the
      context of malaria vector-parasite co-evolution as a function of anthropogenic
      effects.

PMID- 21080967
TI  - Imaging the functional connectivity of the Periaqueductal Gray during genuine and
      sham electroacupuncture treatment.
AB  - BACKGROUND: Electroacupuncture (EA) is currently one of the most popular
      acupuncture modalities. However, the continuous stimulation characteristic of EA
      treatment presents challenges to the use of conventional functional Magnetic
      Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms
      mediating treatment response because of the requirement for brief and
      intermittent stimuli in event related or block designed task paradigms. A
      relatively new analysis method, functional connectivity fMRI (fcMRI), has great
      potential for studying continuous treatment modalities such as EA. In a previous
      study, we found that, compared with sham acupuncture, EA can significantly reduce
      Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain.
      Given the PAG's important role in mediating acupuncture analgesia, in this study
      we investigated functional connectivity with the area of the PAG we previously
      identified and how that connectivity was affected by genuine and sham EA.
      RESULTS: Forty-eight subjects, who were randomly assigned to receive either
      genuine or sham EA paired with either a high or low expectancy manipulation,
      completed the study. Direct comparison of each treatment mode's functional
      connectivity revealed: significantly greater connectivity between the PAG, left
      posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus
      sham; significantly greater connectivity between the PAG and right anterior
      insula for the contrast of sham minus genuine; no significant differences in
      connectivity between different contrasts of the two expectancy levels.
      CONCLUSIONS: Our findings indicate the intrinsic functional connectivity changes
      among key brain regions in the pain matrix and default mode network during
      genuine EA compared with sham EA. We speculate that continuous genuine EA
      stimulation can modify the coupling of spontaneous activity in brain regions that
      play a role in modulating pain perception.

PMID- 21080970
TI  - Avoidable readmission in Hong Kong--system, clinician, patient or social factor?
AB  - BACKGROUND: Studies that identify reasons for readmissions are gaining importance
      in the light of the changing demographics worldwide which has led to greater
      demand for hospital beds. It is essential to profile the prevalence of avoidable
      readmissions and understand its drivers so as to develop possible interventions
      for reducing readmissions that are preventable. The aim of this study is to
      identify the magnitude of avoidable readmissions, its contributing factors and
      costs in Hong Kong. METHODS: This was a retrospective analysis of 332,453
      inpatient admissions in the Medical specialty in public hospital system in Hong
      Kong in year 2007. A stratified random sample of patients with unplanned
      readmission within 30 days after discharge was selected for medical record
      reviews. Eight physicians reviewed patients' medical records and classified
      whether a readmission was avoidable according to an assessment checklist. The
      results were correlated with hospital inpatient data. RESULTS: It was found that
      40.8% of the 603 unplanned readmissions were judged avoidable by the reviewers.
      Avoidable readmissions were due to: clinician factor (42.3%) including low
      threshold for admission and premature discharge etc.; patient factor (including
      medical and health factor) (41.9%) such as relapse or progress of previous
      complaint, and compliance problems etc., followed by system factor (14.6%)
      including inadequate discharge planning, inadequate palliative care/terminal
      care, etc., and social factor (1.2%) such as carer system, lack of support and
      community services. After adjusting for patients' age, gender, principal
      diagnosis at previous discharge and readmission hospitals, the risk factors for
      avoidable readmissions in the total population i.e. all acute care admissions
      irrespective of whether there was a readmission or not, included patients with a
      longer length of stay, and with higher number of hospitalizations and attendance
      in public outpatient clinics and Accident and Emergency departments in the past
      12 months. In the analysis of only unplanned readmissions, it was found that the
      concordance of the principal diagnosis for admission and readmission, and shorter
      time period between discharge and readmission were associated with avoidable
      readmissions. CONCLUSIONS: Our study found that almost half of the readmissions
      could have been prevented. They had been mainly due to clinician and patient
      factors, in particular, both of which were intimately related to clinical
      management and patient care. These readmissions could be prevented by a system of
      ongoing clinical review to examine the clinical practice/decision for discharge,
      and improving clinical care and enhancing patient knowledge of the early warning
      signs for relapse. The importance of adequate and appropriate ambulatory care to
      support the patients in the community was also a key finding to reduce avoidable
      readmissions. Education on patient self-management should also be enhanced to
      minimize the patient factors with regard to avoidable readmission. Our findings
      thus provide important insights into the development of an effective discharge
      planning system which should place patients and carers as the primacy focus of
      care by engaging them along with the healthcare professionals in the whole
      discharge planning process.

PMID- 21080969
TI  - Steroid receptor coactivator 1 deficiency increases MMTV-neu mediated tumor
      latency and differentiation specific gene expression, decreases metastasis, and
      inhibits response to PPAR ligands.
AB  - BACKGROUND: The peroxisome proliferator activated receptor (PPAR) subgroup of the
      nuclear hormone receptor superfamily is activated by a variety of natural and
      synthetic ligands. PPARs can heterodimerize with retinoid X receptors, which have
      homology to other members of the nuclear receptor superfamily. Ligand binding to
      PPAR/RXRs results in recruitment of transcriptional coactivator proteins such as
      steroid receptor coactivator 1 (SRC-1) and CREB binding protein (CBP). Both SRC-1
      and CBP are histone acetyltransferases, which by modifying nucleosomal histones,
      produce more open chromatin structure and increase transcriptional activity.
      Nuclear hormone receptors can recruit limiting amounts of coactivators from other
      transcription factor binding sites such as AP-1, thereby inhibiting the activity
      of AP-1 target genes. PPAR and RXR ligands have been used in experimental breast
      cancer therapy. The role of coactivator expression in mammary tumorigenesis and
      response to drug therapy has been the subject of recent studies. METHODS: We
      examined the effects of loss of SRC-1 on MMTV-neu mediated mammary tumorigenesis.
      RESULTS: SRC-1 null mutation in mammary tumor prone mice increased the tumor
      latency period, reduced tumor proliferation index and metastasis, inhibited
      response to PPAR and RXR ligands, and induced genes involved in mammary gland
      differentiation. We also examined human breast cancer cell lines overexpressing
      SRC-1 or CBP. Coactivator overexpression increased cellular proliferation with
      resistance to PPAR and RXR ligands and remodeled chromatin of the proximal
      epidermal growth factor receptor promoter. CONCLUSIONS: These results indicate
      that histone acetyltransferases play key roles in mammary tumorigenesis and
      response to anti-proliferative therapies.

PMID- 21080972
TI  - The QUIT-PRIMO provider-patient Internet-delivered smoking cessation referral
      intervention: a cluster-randomized comparative effectiveness trial: study
      protocol.
AB  - BACKGROUND: Although screening for tobacco use is increasing with electronic
      health records and standard protocols, other tobacco-control activities, such as
      referral of patients to cessation resources, is quite low. In the QUIT-PRIMO
      study, an online referral portal will allow providers to enter smokers' email
      addresses into the system. Upon returning home, the smokers will receive
      automated emails providing education about tobacco cessation and encouragement to
      use the patient smoking cessation website (with interactive tools, educational
      resources, motivational email messages, secure messaging with a tobacco treatment
      specialist, and online support group). METHODS: The informatics system will be
      evaluated in a comparative effectiveness trial of 160 community-based primary
      care practices, cluster-randomized at the practice level. In the QUIT-PRIMO
      intervention, patients will be provided a paper information-prescription referral
      and then "e-referred" to the system. In the comparison group, patients will
      receive only the paper-based information-prescription referral with the website
      address. Once patients go to the website, they are subsequently randomized within
      practices to either a standard patient smoking cessation website or an augmented
      version with access to a tobacco treatment specialist online, motivational
      emails, and an online support group. We will compare intervention and control
      practice participation (referral rates) and patient participation (proportion
      referred who go to the website). We will then compare the effectiveness of the
      standard and augmented patient websites. DISCUSSION: Our goal is to evaluate an
      integrated informatics solution to increase access to web-delivered smoking
      cessation support. We will analyze the impact of this integrated system in terms
      of process (provider e-referral and patient login) and patient outcomes (six
      month smoking cessation). TRIAL REGISTRATION: Web-delivered Provider Intervention
      for Tobacco Control (QUIT-PRIMO) - a randomized controlled trial: NCT00797628.

PMID- 21080971
TI  - Integrated genomics of susceptibility to alkylator-induced leukemia in mice.
AB  - BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is a secondary,
      generally incurable, malignancy attributable to chemotherapy exposure. Although
      there is a genetic component to t-AML susceptibility in mice, the relevant loci
      and the mechanism(s) by which they contribute to t-AML are largely unknown. An
      improved understanding of susceptibility factors and the biological processes in
      which they act may lead to the development of t-AML prevention strategies.
      RESULTS: In this work we applied an integrated genomics strategy in inbred
      strains of mice to find novel factors that might contribute to susceptibility. We
      found that the pre-exposure transcriptional state of hematopoietic
      stem/progenitor cells predicts susceptibility status. More than 900 genes were
      differentially expressed between susceptible and resistant strains and were
      highly enriched in the apoptotic program, but it remained unclear which genes, if
      any, contribute directly to t-AML susceptibility. To address this issue, we
      integrated gene expression data with genetic information, including single
      nucleotide polymorphisms (SNPs) and DNA copy number variants (CNVs), to identify
      genetic networks underlying t-AML susceptibility. The 30 t-AML susceptibility
      networks we found are robust: they were validated in independent, previously
      published expression data, and different analytical methods converge on them.
      Further, the networks are enriched in genes involved in cell cycle and DNA repair
      (pathways not discovered in traditional differential expression analysis),
      suggesting that these processes contribute to t-AML susceptibility. Within these
      networks, the putative regulators (e.g., Parp2, Casp9, Polr1b) are the most
      likely to have a non-redundant role in the pathogenesis of t-AML. While
      identifying these networks, we found that current CNVR and SNP-based haplotype
      maps in mice represented distinct sources of genetic variation contributing to
      expression variation, implying that mapping studies utilizing either source alone
      will have reduced sensitivity. CONCLUSION: The identification and prioritization
      of genes and networks not previously implicated in t-AML generates novel
      hypotheses on the biology and treatment of this disease that will be the focus of
      future research.

PMID- 21080973
TI  - Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in
      MC3T3-E1 osteoblastic cells.
AB  - BACKGROUND: Mechanical strain plays a significant role in the regulation of bone
      matrix turnover, which is mediated in part by matrix metalloproteinase (MMP)-13
      and tissue inhibitors of matrix metalloproteinase (TIMP)-1. However, little is
      known about the correlation between mechanical strain and osteoblastic cell
      activities, including extracellular matrix (ECM) metabolism. Herein, we
      determined the effect of different magnitudes of cyclic tensile strain (0%, 6%,
      12%, and 18%) on MMP-13 and TIMP-1 mRNA and protein expression in MC3T3-E1
      osteoblasts. Furthermore, we employed specific inhibitors to examine the role of
      distinct signal transduction pathways known to mediate cellular responses to
      mechanical strain. RESULTS: We identified a magnitude-dependent increase in MMP
      13 and TIMP-1 mRNA and protein levels in response to mechanical strains
      corresponding to 6%, 12%, and 18% elongation. The strain-induced increases in MMP
      13 and TIMP-1 mRNA expression were inhibited by PD098059 and cycloheximide,
      respectively. CONCLUSIONS: Our results suggest a mechanism for the regulation of
      bone matrix metabolism mediated by the differential expression of MMP-13 and TIMP
      1 in response to increasing magnitudes of mechanical strain.

PMID- 21080975
TI  - A survey of core and support activities of communicable disease surveillance
      systems at operating-level CDCs in China.
AB  - BACKGROUND: In recent years, problems like insufficient coordination, low
      efficiency, and heavy working load in national communicable disease surveillance
      systems in China have been pointed out by many researchers. To strengthen the
      national communicable disease surveillance systems becomes an immediate concern.
      Since the World Health Organization has recommended that a structured approach to
      strengthen national communicable disease surveillance must include an evaluation
      to existing systems which usually begins with a systematic description, we
      conducted the first survey for communicable disease surveillance systems in
      China, in order to understand the situation of core and support surveillance
      activities at province-level and county-level centers for disease control and
      prevention (CDCs). METHODS: A nationwide survey was conducted by mail between May
      and October 2006 to investigate the implementation of core and support activities
      of the Notifiable Disease Reporting System (NDRS) and disease-specific
      surveillance systems in all of the 31 province-level and selected 14 county-level
      CDCs in Mainland China The comments on the performance of communicable disease
      surveillance systems were also collected from the directors of CDCs in this
      survey. RESULTS: The core activities of NDRS such as confirmation, reporting and
      analysis and some support activities such as supervision and staff training were
      found sufficient in both province-level and county-level surveyed CDCs, but other
      support activities including information feedback, equipment and financial
      support need to be strengthened in most of the investigated CDCs. A total of 47
      communicable diseases or syndromes were under surveillance at province level, and
      20 diseases or syndromes at county level. The activities among different disease
      specific surveillance systems varied widely. Acute flaccid paralysis (AFP),
      measles and tuberculosis (TB) surveillance systems got relatively high
      recognition both at province level and county level. CONCLUSIONS: China has
      already established a national communicable disease surveillance framework that
      combines NDRS and disease-specific surveillance systems. The core and support
      activities of NDRS were found sufficient, while the implementation of those
      activities varied among different disease-specific surveillance systems.

PMID- 21080974
TI  - Effects of valproic acid on the cell cycle and apoptosis through acetylation of
      histone and tubulin in a scirrhous gastric cancer cell line.
AB  - BACKGROUND: Management of peritoneal dissemination is the most critical problem
      in gastric cancer. This study was performed to investigate the inhibitory effects
      of valproic acid (VPA) on a highly peritoneal-seeding cell line of human
      scirrhous gastric cancer, OCUM-2MD3, and to explore the mechanism and the
      potential of VPA. METHODS: The effects of VPA on the growth of OCUM-2MD3 cells
      were assessed by MTT assay. In addition, paclitaxel (PTX) was combined with VPA
      to evaluate their synergistic effects. HDAC1 and HDAC2 expression were evaluated
      by western blotting in OCUM-2MD3 cells and other gastric cancer cell lines (TMK
      1, MKN-28). The acetylation status of histone H3 and alpha-tubulin after exposure
      to VPA were analyzed by western blotting. The activities of cell cycle regulatory
      proteins and apoptosis-modulating proteins were also examined by western
      blotting. The effects of VPA in vivo were evaluated in a xenograft model, and
      apoptotic activity was assessed by TUNEL assay. RESULTS: OCUM-2MD3 cells showed
      high levels of HDAC1 and HDAC2 expression compared with TMK-1 and MKN-28. The
      concentration of VPA required for significant inhibition of cell viability (P <
      0.05) was 5 mM at 24 h and 0.5 mM at 48 h and 72 h. The inhibition of VPA with
      PTX showed dose-dependent and combinatorial effects. VPA increased acetyl-histone
      H3, acetyl-alpha-tubulin, and p21WAF1 levels accompanied by upregulation of p27,
      caspase 3, and caspase 9, and downregulation of bcl-2, cyclin D1, and survivin.
      In the xenograft model experiment, the mean tumor volume of the VPA-treated group
      was significantly reduced by 36.4%, compared with that of the control group at 4
      weeks after treatment (P < 0.01). The apoptotic index was significantly higher in
      the VPA-treated group (42.3% +/- 3.5%) than in the control group (7.7% +/- 2.5%)
      (P < 0.001). CONCLUSIONS: VPA induced dynamic modulation of histone H3 and alpha
      tubulin acetylation in relation with the anticancer effect and the enhancement of
      PTX in the OCUM-2MD3 cell line. Therefore, VPA in combination with PTX is
      expected to be a promising therapy for peritoneal dissemination of scirrhous
      gastric cancer.

PMID- 21080976
TI  - A cross-sectional study of the number and frequency of terms used to refer to
      knowledge translation in a body of health literature in 2006: a Tower of Babel?
AB  - BACKGROUND: The study of implementing research findings into practice is rapidly
      growing and has acquired many competing names (e.g., dissemination, uptake,
      utilization, translation) and contributing disciplines. The use of multiple terms
      across disciplines pose barriers to communication and progress for applying
      research findings. We sought to establish an inventory of terms describing this
      field and how often authors use them in a collection of health literature
      published in 2006. METHODS: We refer to this field as knowledge translation (KT).
      Terms describing aspects of KT and their definitions were collected from
      literature, the internet, reports, textbooks, and contact with experts. We
      compiled a database of KT and other articles by reading 12 healthcare journals
      representing multiple disciplines. All articles published in these journals in
      2006 were categorized as being KT or not. The KT articles (all KT) were further
      categorized, if possible, for whether they described KT projects or
      implementations (KT application articles), or presented the theoretical basis,
      models, tools, methods, or techniques of KT (KT theory articles). Accuracy was
      checked using duplicate reading. Custom designed software determined how often KT
      terms were used in the titles and abstracts of articles categorized as being KT.
      RESULTS: A total of 2,603 articles were assessed, and 581 were identified as KT
      articles. Of these, 201 described KT applications, and 153 included KT theory. Of
      the 100 KT terms collected, 46 were used by the authors in the titles or
      abstracts of articles categorized as being KT. For all 581 KT articles, eight
      terms or term variations used by authors were highly discriminating for
      separating KT and non-KT articles (p < 0.001): implementation, adoption, quality
      improvement, dissemination, complex intervention (with multiple endings),
      implementation (within three words of) research, and complex intervention. More
      KT terms were associated with KT application articles (n = 13) and KT theory
      articles (n = 18). CONCLUSIONS: We collected 100 terms describing KT research.
      Authors used 46 of them in titles and abstracts of KT articles. Of these,
      approximately half discriminated between KT and non-KT articles. Thus, the need
      for consolidation and consistent use of fewer terms related to KT research is
      evident.

PMID- 21080977
TI  - Bipolar cells in the zebrafish retina.
AB  - Zebrafish are an existing model for genetic and developmental studies due to
      their rapid external development and transparent embryos, which allow easy
      manipulation and observation of early developmental stages. The application of
      the zebrafish model to vision research has allowed for examination of retinal
      development and the characteristics of different retinal cell types, including
      bipolar cells. In particular, bipolar cell development, including
      differentiation, maturation, and gene expression, has been documented, as has
      physiological properties, such as voltage- and ligand-gated currents, and
      neurotransmitter receptor and ion channel expression. Mutant strains and
      transgenic lines have been used to document how bipolar cell connections and/or
      development may be altered, and toxicological studies examining how environmental
      factors may impact bipolar cell activity have been performed. The purpose of this
      paper was to review the existing literature on zebrafish bipolar cells, to
      provide a comprehensive overview of current information pertaining to this
      retinal cell type.

PMID- 21080978
TI  - Prenatal diagnosis of left ventricular aneurysm in association with interruption
      of the aortic arch.
AB  - Left ventricular aneurysms in the foetus are a rare abnormality that can occur in
      isolation or associated with pentalogy of Cantrell. Here, we report a case of a
      foetus with a left ventricular aneurysm in association with interruption of the
      aortic arch, and no features of pentalogy of Cantrell. To our knowledge, this is
      the first report of such an association.

PMID- 21080979
TI  - Usefulness of ambulatory blood pressure monitoring and head-up tilt test in the
      evaluation of paediatric syncope.
AB  - OBJECTIVES: The aim of this study was to investigate the usefulness of ambulatory
      blood pressure monitoring versus head-up tilt test in the evaluation of children
      with a history of syncope. STUDY DESIGN: We considered 146 consecutive children
      with more than one episode of syncope. All patients had a normal
      electrocardiogram at rest and were otherwise considered to be healthy. Forty-six
      patients,19 male, with a mean age of 13.6 plus or minus 5.6 years, were studied
      with a head-up tilt test and 100 patients, 41 male with a mean age of 9.4 plus or
      minus 5.6 years, were studied with ambulatory blood pressure monitoring. Twelve
      patients underwent both procedures. Hypotension during ambulatory blood pressure
      monitoring was defined when mean blood pressure values were lower than the 50th
      centile and the head-up tilt test was positive when syncope occurred. All
      patients were followed for 10 plus or minus 2 months. RESULTS: Ambulatory blood
      pressure monitoring showed postural hypotension in 91% children, while head-up
      tilt test was positive for 54%. In the group of children having both tests, two
      of them were negative for both, 10 of 12 children had a positive ambulatory blood
      pressure monitoring while only five of 10 children had a positive response to
      head-up tilt test. CONCLUSIONS: When a child with a normal resting
      electrocardiogram is referred with a typical history of syncope, the use of
      ambulatory blood pressure monitoring as a non-invasive first step for diagnosis
      of postural hypotension may be more sensitive than the head-up tilt test.
      Behavioural adjustments resolved the continued syncope in most cases. If episodes
      persist then the head-up tilt test is indicated.

PMID- 21080980
TI  - A family with a new elastin gene mutation: broad clinical spectrum, including
      sudden cardiac death.
AB  - Supravalvular aortic stenosis is associated with the Williams-Beuren syndrome,
      but it also occurs in a non-syndromatic congenital form. An elastin gene mutation
      of chromosome 7q11.23 is responsible in both cases. The vascular features are
      identical. These patients have a higher risk of sudden death, particularly when
      undergoing diagnostic or surgical procedures. We report the account of a family
      with a new mutation in the elastin gene. Screening over three generations
      revealed eight affected individuals. The cardiac and vascular malformations
      ranged from mild asymptomatic supravalvular aortic stenosis and isolated
      dysplastic atrioventricular valves to diffuse arterial hypoplasia. Two infants
      presented arteries affected at multiple locations, including the left coronary
      artery. Both died of sudden cardiac death and myocardial ischaemia, one while
      under general anaesthesia for cardiac catheterisation, and the other
      perioperatively. We discuss the pathophysiological aspects in these patients that
      deserve consideration before any general anaesthesia is administered.

PMID- 21080981
TI  - The fantastic year of 2010--and the really hot topic: breast-feeding.

PMID- 21080982
TI  - Lymphatic absorption of alpha-linolenic acid in rats fed flaxseed oil-based
      emulsion.
AB  - The bioavailability of alpha-linolenic acid (ALA) from flaxseed oil in an
      emulsified form v. a non-emulsified form was investigated by using two
      complementary approaches: the first one dealt with the characterisation of the
      flaxseed oil emulsion in in vitro gastrointestinal-like conditions; the second
      one compared the intestinal absorption of ALA in rats fed the two forms of the
      oil. The in vitro study on emulsified flaxseed oil showed that decreasing the pH
      from 7.3 to 1.5 at the physiological temperature (37 degrees C) induced
      instantaneous oil globule coalescence. Some phase separation was observed under
      acidic conditions that vanished after further neutralisation. The lecithin used
      to stabilise the emulsions inhibited TAG hydrolysis by pancreatic lipase. In
      contrast, lipid solubilisation by bile salts (after lipase and phospholipase
      hydrolysis) was favoured by preliminary oil emulsification. The in vivo
      absorption of ALA in thoracic lymph duct-cannulated rats fed flaxseed oil,
      emulsified or non-emulsified, was quantified. Oil emulsification significantly
      favoured the rate and extent of ALA recovery as measured by the maximum ALA
      concentration in the lymph (Cmax = 14 mg/ml at 3 h in the emulsion group v. 9
      mg/ml at 5 h in the oil group; P < 0.05). Likewise, the area under the curve of
      the kinetics was significantly higher in the emulsion group (48 mg * h/ml for
      rats fed emulsion v. 26 mg * h/ml for rats fed oil; P < 0.05). On the whole, ALA
      bioavailability was improved with flaxseed oil ingested in an emulsified state.
      Data obtained from the in vitro studies helped to partly interpret the
      physiological results.

PMID- 21080984
TI  - ENT morbidity at high altitude.
AB  - BACKGROUND: People suffer unique health problems in high altitude areas, due to
      such factors as elevation, aircraft ascent and descent, extreme cold, hypoxia,
      hypobaria, and low relative humidity. This study was conducted to evaluate ENT
      morbidity at high altitude. METHODS: Serving soldiers introduced to a high
      altitude environment who presented with various ENT symptoms were examined to
      identify ENT disease. In addition, patients undergoing hyperbaric chamber
      therapy, tracheostomy and treatment of cold injuries were also examined for ENT
      problems. RESULTS: The following were detected: 13 cases of otic barotrauma, 11
      cases of sinus barotrauma, three cases of vertigo, six cases of pinna frostbite,
      three cases of barotrauma caused by hyperbaric chamber therapy, an unusually high
      incidence of epistaxis, and innumerable patients with high altitude pharyngitis.
      CONCLUSION: Diseases of the ear, nose and throat contribute significantly to high
      altitude morbidity. In a military context, health education of troops is
      necessary to avoid such problems.

PMID- 21080983
TI  - Comparison between an interactive web-based self-administered 24 h dietary record
      and an interview by a dietitian for large-scale epidemiological studies.
AB  - Online self-administered data collection, by reducing the logistic burden and
      cost, could advantageously replace classical methods based on dietitian's
      interviews when assessing dietary intake in large epidemiological studies.
      Studies comparing such new instruments with traditional methods are necessary.
      Our objective was to compare one NutriNet-Sante web-based self-administered 24 h
      dietary record with one 24 h recall carried out by a dietitian. Subjects
      completed the web-based record, which was followed the next day by a dietitian
      conducted 24 h recall by telephone (corresponding to the same day and using the
      same computerised interface for data entry). The subjects were 147 volunteers
      aged 48-75 years (women 59.2 %). The study was conducted in February 2009 in
      France. Agreement was assessed by intraclass correlation coefficients (ICC) for
      foods and energy-adjusted Pearson's correlations for nutrients. Agreement between
      the two methods was high, although it may have been overestimated because the two
      assessments were consecutive to one another. Among consumers only, the median of
      ICC for foods was 0.8 in men and 0.7 in women (range 0.5-0.9). The median of
      energy-adjusted Pearson's correlations for nutrients was 0.8 in both sexes (range
      0.6-0.9). The mean Pearson correlation was higher in subjects <= 60 years (P =
      0.02) and in those who declared being 'experienced/expert' with computers (P =
      0.0003), but no difference was observed according to educational level (P =
      0.12). The mean completion time was similar between the two methods (median for
      both methods: 25 min). The web-based method was preferred by 66.1 % of users. Our
      web-based dietary assessment, permitting considerable logistic simplification and
      cost savings, may be highly advantageous for large population-based surveys.

PMID- 21080985
TI  - Electrocardiogram screening of deaf children for long QT syndrome: are we
      following UK national guidelines?
AB  - INTRODUCTION: Jervell-Lange-Nielsen syndrome is characterised by congenital
      deafness and a long QT interval on electrocardiography. AIM: (1) To survey UK
      national practice regarding electrocardiography screening of deaf children
      referred to cochlear implant centres, performed to evaluate for prolonged QT
      interval as recommended by national guidelines, and (2) to review local practice.
      METHODS: Data were collected via a questionnaire sent to all UK cochlear implant
      centres, and via review of the medical records of a local cochlear implant centre
      database. RESULTS: Eight (42 per cent) of the 19 cochlear implant centres
      surveyed performed electrocardiographic screening. Thirteen cases of long QT
      syndrome were reported in seven centres, with two related deaths. In our local
      cochlear implant centre, 14 (7.1 per cent) of 193 children had abnormal
      electrocardiograms; one definite long QT syndrome case and 13 borderline cases
      were identified. CONCLUSION: Despite clear national guidelines for
      electrocardiographic screening of deaf children, there is wide variation in
      practice. Our local practice of performing investigations, including
      electrocardiography, during magnetic resonance imaging sedation has been very
      successful. Electrocardiograms should be reviewed by trained clinicians, and
      corrected QT intervals should be calculated manually.

PMID- 21080987
TI  - Suffer little children.

PMID- 21080989
TI  - Addressing the demand for termination of pregnancy services in district health
      facilities in Johannesburg.

PMID- 21080990
TI  - Solubility tests and the peripheral blood method for screening for sickle-cell
      disease.

PMID- 21080991
TI  - Approval of chronic medication.

PMID- 21080992
TI  - Gvt crafts its own hospital quality standards, sans world class local body.

PMID- 21080995
TI  - World Cup 2010 and acute pain in the neck.

PMID- 21080996
TI  - Mental health services funding and development in KwaZulu-Natal: a tale of
      inequity and neglect.
AB  - BACKGROUND: Globally, a significant 'mental health gap' exists between the major
      burden of mental and substance use disorders and the provision of psychiatric and
      mental health services. As a signatory to the UN Convention on the Rights of
      Persons with Disabilities, South Africa has committed itself to transformation
      aimed at ending the inequities that characterise mental health service provision
      and 'closing the gap'. METHODOLOGY: Budget allocations over a 5-year period to 6
      psychiatric and 7 general hospitals in KwaZulu-Natal (KZN) are compared and
      current numbers of psychiatric beds and psychiatric personnel in that province
      are contrasted with the numbers required to comply with national norms. RESULTS:
      The mean increase in budget allocations to public psychiatric hospitals was 3.8%
      per annum, while that to general hospitals over the same period was 10.2% per
      annum. The median cumulative budget increase for psychiatric hospitals was
      significantly lower than that of general hospitals (Mann-Whitney U-test,
      p=0.001). No psychiatric hospitals received specific funding for tertiary
      services development. KZN has 25% of the acute psychiatric beds and 25% of the
      psychiatrists required to comply with national norms, with the most serious
      shortages experienced in northern KZN. There are 0.38 psychiatrists per 100 000
      population in KZN. CONCLUSION: Inequitable funding, inadequate facilities and
      significant shortages of mental health professionals pervade the mental health
      and psychiatric services in KZN. There is little evidence of government abiding
      by its public commitments to redress the inequities that characterise mental
      health services.

PMID- 21080997
TI  - Impact of the South African Mental Health Care Act No. 17 of 2002 on regional and
      district hospitals designated for mental health care in KwaZulu-Natal.
AB  - BACKGROUND: The South African Mental Health Care Act (the Act) No. 17 of 2002
      stipulated that regional and district hospitals be designated to admit, observe
      and treat mental health care users (MHCUs) for 72 hours before they are
      transferred to a psychiatric hospital. METHODS: Medical managers in 49
      'designated' hospitals in KwaZulu-Natal (KZN) were surveyed on infrastructure,
      staffing, administrative requirements and mental health care user case load
      pertaining to the Act for the month of July 2009. RESULTS: Thirty-six (73.4%)
      hospitals responded to the survey; 30 (83.3%) stated that the Act improved mental
      health care for MHCUs through the protection of their rights, provision of least
      restrictive care, and reduction of discrimination; 10 (27.8%) had a psychiatric
      unit and, of the remaining 26 hospitals, 11 (30.6%) had general ward beds
      dedicated for psychiatric admissions; 16 (44.4%) had some form of seclusion
      facility; and 24 (66.7%) provided an outpatient psychiatric service. Seventy-six
      per cent of admissions were involuntary or assisted. Thirteen of the 32 (40.6%)
      state psychiatrists in KZN were employed at 8 of these hospitals. Designated
      hospitals expressed dissatisfaction with the substantial administrative load
      required by the Act. The Review Board had not visited 29 (80.6 %) hospitals in
      the preceding 6 months. CONCLUSION: Although 'designated' hospitals admit and
      treat assisted and involuntary MHCUs, they do so against a backdrop of inadequate
      infrastructure and staff, a high administrative load, and a low level of contact
      with Review Boards.

PMID- 21080998
TI  - Earlier HIV diagnosis--are mobile services the answer?
AB  - OBJECTIVES: To assess the age and gender differences of clients accessing mobile
      HIV counselling and testing (HCT) compared with clients accessing facility-based
      testing, and to determine the difference in HIV prevalence and baseline CD4
      counts. METHODS: This was a prospective observational cross-sectional study of 3
      different HIV testing services in Cape Town. We compared data on age, sex, HIV
      status and CD4 counts collected between August and December 2008 from a mobile
      testing service (known as the Tutu Tester), a primary health care clinic, and a
      district hospital. RESULTS: A total of 3 820 individuals were tested: 2 499 at
      the mobile, 657 at the clinic, and 664 at the hospital. Age and sex distribution
      differed across services, with the mobile testing more men and older individuals.
      HIV prevalence was lowest at the mobile (5.9%) compared with the clinic (18.0%)
      and hospital (23.3%). Of the HIV-infected individuals from the mobile service,
      75% had a CD4 count higher than 350 cells/ul compared with 48% and 32%
      respectively at the clinic and hospital. Age- and sex-adjusted risk for HIV
      positivity was 3.5 and 4.9 times higher in the clinic-based and hospital-based
      services compared with the mobile service. CONCLUSION: Mobile services are
      accessed by a different population compared with facility-based services. Mobile
      service clients were more likely to be male and less likely to be HIV-positive,
      and those infected presented with earlier disease.

PMID- 21080999
TI  - Differences in access and patient outcomes across antiretroviral treatment
      clinics in the Free State province: a prospective cohort study.
AB  - OBJECTIVE: To assess differences in access to antiretroviral treatment (ART) and
      patient outcomes across public sector treatment facilities in the Free State
      province, South Africa. DESIGN: Prospective cohort study with retrospective
      database linkage. We analysed data on patients enrolled in the treatment
      programme across 36 facilities between May 2004 and December 2007, and assessed
      percentage initiating ART and percentage dead at 1 year after enrolment.
      Multivariable logistic regression was used to estimate associations of facility
      level and patient-level characteristics with both mortality and treatment status.
      RESULTS: Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8
      778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied
      greatly across facilities and more variability was explained by facility-level
      factors than by patient-level factors. The odds of starting treatment within 1
      year improved over calendar time. Patients enrolled in facilities with treatment
      initiation available on site had higher odds of starting treatment and lower odds
      of death at 1 year compared with those enrolled in facilities that did not offer
      treatment initiation. Patients were less likely to start treatment if they were
      male, severely immunosuppressed (CD4 count <=50 cells/ul), or underweight (<50
      kg). Men were also more likely to die in the first year after enrolment.
      CONCLUSIONS: Although increasing numbers of patients started ART between 2004 and
      2007, many patients died before accessing ART. Patient outcomes could be improved
      by decentralisation of treatment services, fast-tracking the most immunodeficient
      patients and improving access, especially for men.

PMID- 21081000
TI  - Shallow-water spinal injuries--devastating but preventable.
AB  - BACKGROUND: Shallow-water diving injuries have devastating consequences for
      patients and their families, requiring intensive use of resources in both the
      acute and rehabilitative phases of injury. With the final clinical outcome often
      poor, the question is raised as to whether a target group can be identified for
      whom to implement a preventive programme. OBJECTIVE: To evaluate the
      demographics, clinical features and outcomes of shallow-water diving injuries in
      an acute spinal cord injury (ASCI) unit. MATERIALS AND METHODS: All patients
      admitted to the ASCI unit with diving-related injuries were entered into the
      study. Data regarding demographics, injury profile and subsequent management were
      collated. All case notes and X-rays were reviewed. Ethical approval was obtained.
      RESULTS: Forty-six patients were reviewed from 19 April 2003 to 8 February 2009.
      A steady annual increase in diving injuries was noted. A very specific patient
      profile was identified: 91% male incidence, average age 23 years, 37% admitted
      alcohol use, with a summer-time prevalence. Compression-flexion type injuries
      were most prevalent, with an orthopaedic level of C5 and neurological level of C4
      being the most common injury sites. A third of diving injuries occurred in the
      sea, 20% in swimming pools, 20% in rivers, 11% in tidal pools and 4% in dams.
      CONCLUSION: A very specific patient profile was identified, and the severity of
      shallow-water diving injuries was confirmed. No current preventive programme
      exists except for a single television advertisement. These data will be used to
      motivate further educational and preventive programmes for reducing the incidence
      of diving-related injuries.

PMID- 21081001
TI  - Standards for the reporting of sex/sexual activity of minors in a research
      context.

PMID- 21081002
TI  - Home self-testing for HIV: AIDS exceptionalism gone wrong.

PMID- 21081003
TI  - Provisions for consent by children to medical treatment and surgical operations,
      and duties to report child and aged persons abuse: 1 April 2010.

PMID- 21081004
TI  - Recruiting heterosexual couples from the general population for studies in rural
      South Africa--challenges and lessons (Project Accept, HPTN 043).

PMID- 21081005
TI  - Mental health advocacy--lessons from HIV activism.

PMID- 21081007
TI  - eTV's faith healing advertorial 'fatal'--TAC.

PMID- 21081008
TI  - A better deal for lung-diseased miners?

PMID- 21081009
TI  - Medical indemnity regulations: MPS maintains commitment to South Africa.

PMID- 21081012
TI  - CPD Questionnaire.

PMID- 21081013
TI  - Millennium Development Goals: How are we doing?

PMID- 21081015
TI  - HPCSA disciplinary action - 'Custodian of professional morals?'.

PMID- 21081016
TI  - Ethical challenges in an age of overpopulation.

PMID- 21081017
TI  - Clumsy patient-friendly regulations could strip 25 000 of MPS cover.
AB  - The Medical Protection Society (MPS), a financial and legal haven for 25 000
      South African health care practitioners and reliable source of recompense for
      countless casualties of care, may be legislated out of the country. Unless
      negotiations scheduled over the next 14 months result in amendments to the
      regulations, due to kick in this December, the MPS will from December 2011 be
      unable to protect its members from the legal consequences of any post-2011
      adverse event. The new requirement is that private health care practitioners must
      sign up for cover using only insurers or indemnifiers registered under Section 7
      of the Short-term Insurance Act, something the MPS, which is not a short-term
      insurer, cannot do.

PMID- 21081018
TI  - Possible MPS eviction 'an unmitigated disaster' - patient litigator.
AB  - One of the country's top patient litigators and a seasoned opponent of the
      Medical Protection Society (MPS), Mervyn Joseph, says forcing the MPS out would
      prove an 'unmitigated disaster' for patients and doctors alike. Joseph, who has
      over the years received 'substantial' compensation from the MPS on behalf of
      patients, says he would rather litigate against an informed, professional
      opponent with solid financial reserves than 'fight tooth and nail against someone
      bent only on avoiding both the merits of an action and paying justifiable
      quantum'. Warning that the highly specialised health care indemnity/insurance
      market could be flooded with unschooled and/or under-funded newcomers, Joseph
      cited a current defendant whose insurers he is suing to prevent their reneging on
      their contractual obligation to cover the doctor in terms of his policy.

PMID- 21081019
TI  - Protection of human participants in health research - a comparison of some US
      Federal Regulations and South African Research Ethics guidelines.
AB  - In response to criticism of ethical review of a South African clinical trial, we
      contrast aspects of the United States Common Rule with South African research
      ethics requirements. In the USA the Common Rule does not apply to all health
      research and allows many exemptions from ethics review and waivers of informed
      consent. At a structural level research ethics review in South Africa is in many
      cases equivalent to the US institutional review board (IRB) and Office for Human
      Research Protections (OHRP) oversight system, is wider reaching, and has no
      exclusions.

PMID- 21081020
TI  - Maternal deaths associated with eclampsia in South Africa: Lessons to learn from
      the confidential enquiries into maternal deaths, 2005 - 2007.
AB  - Eclampsia is the commonest direct cause of maternal death in South Africa. The
      latest Saving Mothers Report (2005-2007) indicates that there were 622 maternal
      deaths due to hypertensive disorders of pregnancy. Of these, 334 (55.3%) were due
      to eclampsia; of the eclamptic deaths, 50 were over the age of 35 years and 83
      were under 20 years old. Avoidable factors involved patient related factors
      (mainly delay in seeking help), administrative factors (mainly delay in
      transport) and health personnel issues (mainly due to delay in referring
      patients). The major causes of death were cerebrovascular accidents and cardiac
      failure. The majority of deaths due to cardiac failure were due to pulmonary
      oedema. To reduce deaths from eclampsia, more attention must be given to the
      detection of pre-eclampsia; the provision of information on the advantages of
      antenatal care to the population at large and training of health professions in
      the management of obstetric emergencies.

PMID- 21081021
TI  - Cytomegalovirus duodenitis, pseudotumour and cholangiopathy in advanced HIV.

PMID- 21081022
TI  - Bryan williams.

PMID- 21081023
TI  - Davey's Companion to Surgery in Africa. 3rd ed.

PMID- 21081024
TI  - Rotational conjunctival flap surgery reduces recurrence of pterygium.
AB  - We aimed to compare the recurrence rate following primary pterygium surgery using
      two different techniques, i.e. simple conjunctival closure (SCC) and rotational
      conjunctival flap (RCF). Postoperative discomfort and complications were also
      investigated in these patients.

PMID- 21081025
TI  - Heliotherapy: A South African perspective.
AB  - The research objective was to gather and collate data that will enable
      dermatologists to quantify exposure to solar radiation so that they can give
      accurate advice to patients using heliotherapy, thereby minimising harm from sun
      exposure. Other patients can also be advised regarding ultraviolet index (UVI)
      and sun safety. The concept of minimal erythema dose per hour (MED/h) may be
      useful in future research into solar radiation and its effects on skin cancer.

PMID- 21081026
TI  - Helicobacter pylori prevalence in dyspeptic patients in the Eastern Cape province
      - race and disease status.
AB  - Objectives. We examined Helicobacter pylori infection in patients with gastric
      related morbidities at Livingstone Hospital, Port Elizabeth, to determine the
      prevalence and risk factors for infection according to race, endoscopic
      diagnosis, age and sex. Methods. Gastric biopsies were collected from 254
      consecutive patients and H. pylori isolated on Columbia agar base supplemented
      with 7% sheep's blood and Skirrow's supplement containing trimethoprim (2.5 mg),
      vancomycin (5 mg) and cefsulodin (2.5 mg). Amphotericin (2.5 mg) was added to the
      medium. Recovered isolates were identified following standard microbiology and
      biochemical techniques. Presumptive isolates were further confirmed by polymerase
      chain reaction (PCR) targeting the glmM gene. Fisher's exact test was used to
      assess the univariate association between H. pylori infection and the possible
      risk factors. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      were calculated to measure the strength of association, using EPI INFO 3.41
      software. P-values <0.05 were required for significance. Results. The overall
      prevalence of H. pylori was 66.1% (168/254). Of the 168 positive subjects, H.
      pylori prevalence was highest in patients with non-ulcer dyspepsia (NUD) (32.7%;
      55/168), and lowest (0%; 0/168) in those with atypical oesophageal reflux disease
      and gastroduodenitis, respectively. The prevalence of infection was highest among
      coloureds (68.4%; 89/130) and lowest in whites (59.5%; 25/ 42). Prevalence
      increased with age. Conclusion. The prevalence of H. pylori is high in dyspeptic
      patients in Eastern Cape Province. Gender, antibiotic treatment and alcohol
      consumption may be risk factors for infection. These findings are of clinical and
      epidemiological significance.

PMID- 21081027
TI  - Pharmacologic testing in Horner's syndrome - a new paradigm.
AB  - For more than three decades, topical cocaine has been used to confirm the
      diagnosis and hydroxyamphetamine to localise the causative lesion in
      oculosympathetic palsy or Horner's syndrome. More recently, other drugs have
      demonstrated the ability to point to the diagnosis or anatomical site.
      Apraclonidine and phenylephrine, given their similar diagnostic efficacy and
      increased availability, may have superseded cocaine and hydroxyamphetamine as
      first-line pharmacological testing agents in Horner's syndrome.

PMID- 21081028
TI  - Genetic variations in androgen metabolism genes and associations with prostate
      cancer in South African men.
AB  - Background. In South Africa white men have the highest incidence of prostate
      cancer (PCa), coloured (mixed ancestry) men have an intermediate incidence, and
      low incidences are reported for black and Asian men. It has been suggested that
      ethnic differences in incidence and mortality of PCa are related to genetic
      variations in genes that regulate androgen metabolism. We investigated the role
      of genetic variants in the androgen metabolism genes and the probability of
      developing PCa in South African coloured and white men. Methods. Genotype and
      allele counts and frequencies of single nucleotide polymorphisms (SNPs) in
      CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured men (160 case individuals,
      146 control individuals) and white men (121 case individuals, 141 control
      individuals). Results. A genetic association indicating an increased probability
      of developing PCa was observed with the G allele of the SNP rs2740574 in CYP3A4
      in coloured men, the A allele of rs776746 (CYP3A5) and the G allele of rs2740574
      (CYP3A4) in white men, and the G allele of rs2740574 and the C allele of rs501275
      (CYP3A43) in the combined ethnic groups analysis. In addition, we identified
      allele combinations (termed haplotypes) with significantly higher frequencies in
      the PCa case individuals than in the control individuals. Conclusions. The
      findings support the role of variants in genes that regulate androgen metabolism
      and the probability of developing PCa. The study paves the way to identify other
      genetic associations in South African men, and to establish genetic profiles that
      could be used to determine disease progression and prognosis.

PMID- 21081029
TI  - South African guideline for management of ischaemic stroke and transient
      ischaemic attack 2010: a guideline from the South African Stroke Society (SASS)
      and the SASS Writing Committee.
AB  - BACKGROUND: Stroke is a leading cause of death and disability in South Africa. An
      increase in the burden of stroke is predicted as the population is undergoing a
      rapid epidemiological transition with increased exposure to, and development of,
      stroke risk factors, together with aging of the population. Objective. The
      objective was to update the guideline published in 2000, to place the
      recommendations within the current South African context, and to grade evidence
      according to the level of scientific rigour. RECOMMENDATIONS: Ideally, all
      patients with acute stroke should be managed in a dedicated stroke unit. There is
      ample evidence that protocol-driven multidisciplinary stroke unit care within a
      hospital improves recovery from stroke. Treatment in a stroke unit has been shown
      to reduce mortality as well as reduce the likelihood of dependency after stroke.
      An effective stroke service requires the establishment of a seamless network
      consisting of acute stroke units, post-acute care and rehabilitation, and further
      care in the community. Primary preventive measures reduce stroke incidence and
      should be universally available and actively promoted at all levels of health
      care in South Africa. Successful care of a stroke patient begins with recognition
      by the public and health professionals that stroke should be considered an
      emergency. Avoiding delay should be the major aim of the prehospital phase of
      acute stroke care. Acute stroke or transient ischaemic attack (TIA) should be
      treated as a medical emergency and evaluated with minimum delay. General
      supportive treatment is emphasised and is directed at maintaining homeostasis and
      the treatment of complications. Intravenous thrombolytic therapy with recombinant
      tissue plasminogen activator (tPA) is an accepted therapy for acute ischaemic
      stroke within 4.5 hours of onset of symptoms, but can only be administered at
      centres with specific resources. Awareness and treatment of the neurological and
      systemic complications of acute stroke are an integral part of management.
      Patients with suspected TIA and minor stroke with early spontaneous recovery
      should be evaluated as soon as possible after an event. Brain imaging is
      recommended, and non-invasive imaging of the cervicocephalic vessels should be
      performed urgently and routinely as part of the evaluation. Carotid
      endarterectomy (CEA) is recommended for patients with severe (70 - 99%)
      ipsilateral stenosis, and the procedure should be performed as soon as possible
      after the last ischaemic event - ideally within 2 weeks - in centres with a peri
      operative complication rate (all strokes and death) of less than 6%. Survivors of
      a TIA or stroke have an increased risk of another stroke, which is a major source
      of increased mortality and morbidity. Secondary prevention strategies are aimed
      at reducing this risk. Stroke rehabilitation is a goal-orientated process that
      attempts to obtain maximum function in patients who have had strokes and who
      suffer from a combination of physical, cognitive and language disabilities.

PMID- 21081031
TI  - Accreditation of training courses in good clinical practice.

PMID- 21081030
TI  - The human genome and molecular medicine - promises and pitfalls.

PMID- 21081032
TI  - The most accurate spear at Hlabisa - a Goko doctor.
AB  - Every public hospital, especially a rural one, needs a skonkwane or anchor person
      who shoulders responsibility, leads by example, initiates or maintains efficient
      systems and motivates staff. Yet few have one, let alone one who is black, female
      and a role model. So when Dr Mmabatho Kekana, 52 years old, the medical manager
      at Hlabisa Hospital in the remote Umkhanyakude District in the far northern
      KwaZulu-Natal coastal region, was nominated by her peers for Rural Doctor of the
      Year, she was the sure-fire favourite. Confirming her victory, the Rural Doctors
      Association of Southern Africa (RuDASA) selection committee member, Dr Alma de
      Vries, said, 'she showed us what can be done to turn a hospital around. She's an
      example of what our health minister, Dr Aaron Motsaoledi, so often speaks of --
      good hospital management. Doctors get disgruntled very quickly when management is
      poor,' she added.

PMID- 21081033
TI  - FASD -- De Aar mums get beyond the 'tippling point'.
AB  - When most of the low-income folk in the 'ghost train' town of De Aar began
      remonstrating with any pregnant mother who was boozing, excited campaigners
      thought they'd broken through the 'tippling point'. However, their research
      colleagues proved they'd gone even further -- the dedicated local platoon of
      social workers, nurses, therapists and volunteers had in three short years
      reduced the prevalence of fetal alcohol spectrum disorder (FASD) by 30%. This is
      in a town with the worst recorded FASD prevalence in any single community in the
      world, where 120 out of every 1 000 residents suffer from FASD (12%).

PMID- 21081037
TI  - [The current concepts of closed chest drainage in lobectomy of lung cancer].
AB  - It is widely accepted by most thoracic surgeons that a complete control on fluid
      and air in the pleural space could only be maintained by conventional closed
      chest drainage (two chest tubes). With the development of medical models and
      devices in pneumonectomy, the validity of this concept is being questioned. In
      this review, we summarized that: the current situation and problems of closed
      chest drainage; the advantage and disadvantage of water seal with or without
      suction on chest drainage; and the advances and contradiction of single chest
      tube drainage after pneumonectomy.

PMID- 21081036
TI  - [The molecular pathogenesis of small cell lung cancer].

PMID- 21081038
TI  - [Prokaryotic expression and purification of human TLE1 N-terminal Q domain
      fragment and production of its polyclonal antibody].
AB  - BACKGROUND: TLE1 is an important protein in regulating Wnt, Notch and EGFR
      signaling pathways. The TLE1 N-terminal Q domain regulates the pathways by
      mediating its oligomerization and interaction with LEF1. The aim of this study is
      to construct the human TLE1 N-terminal Q domain fragment in prokaryotic
      expression system, express and purify protein TLE1 N-terminal Q domain and
      prepare its polyclonal antibody. METHODS: The sequence of TLE1 N-terminal Q
      domain obtained by PCR from human lung adenocarcinoma cDNA, was cloned into the
      prokaryotic expression vector pGEX-4T-1 containing Glutathione S-transferase
      (GST). Vector pGEX-4T1-TLE1-Q was transformed into E.coli BL21 condon plus. The
      GST-TLE1-Q(1-136) fusion protein was induced by IPTG, digested by Thrombin,
      purified with glutathione-sepharose beads and FPLC, identified by SDS-PAGE. Then
      rabbits were immunized with the purified protein TLE1-Q(1-136) for obtaining the
      antiserum. The titers and specificity of antibodies were measured by ELISA and
      Western blot. RESULTS: The PCR identification and the sequencing of recombinant
      plasmid demonstrated that vector pGEX-4T1-TLE1-Q was successfully constructed.
      The SDS-PAGE shows target protein (14,000 Da) is the interest protein TLE1-Q(1
      136). The TLE1 N-terminal Q domain fragment TLE1-Q(1-136) and its polyclonal
      antibody have been acquired, with an antibody titer of 1:20,000. CONCLUSIONS:
      Expression vector pGEX-4T1-TLE1-Q is correctly constructed. The TLE1 N-terminal Q
      domain fragment TLE1-Q(1-136) and its polyclonal antibody have been acquired.
      These work established the foundation for further biological study between TLE1
      and lung cancers.

PMID- 21081039
TI  - Prospective analysis on survival outcomes of nonsmall cell lung cancer stages
      over IIIb treated with HangAm-Dan.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) stages over IIIb still remain as
      an intractable disease. Survival rate of NSCLC stages over IIIb could be
      increased through chemotherapy and radiation, but results are not satisfactory.
      Oriental medicine herbal formula, HangAm-Dan (HAD) has been developed for anti
      tumor purpose and several previous studies have already reported its effects. The
      aim of this study is to assess HAD's efficacy on prolonging the survival rate of
      NSCLC stages over IIIb. METHODS: We have administered 3 000 mg of HAD daily to
      patients. The study included 74 first visit patients of East-West Cancer Center
      (EWCC) from November 2007 to April 2008, diagnosed with inoperable NSCLC stages
      over IIIb. Among them, 30 patients were in HAD group and 44 patients were in
      combined group with conventional therapy and HAD. We have observed and analyzed
      their overall survival. RESULTS: Of total 74 patients, overall 1 year, 2 year
      survival rates and the median survival time were 62.1%, 34.9% and 17.0 months
      (95%CI: 12.9-21.1). NSCLC stage IIIb patients showed higher survival rates than
      NSCLC stage IV patients (P=0.408). The 1 year, 2 year survival rates and the
      median survival time of the combined group were 70.5%, 37.9% and 20.0 months
      (95%CI: 16.4-24.6). In HAD group, the 1 year, 2 year survival rates and the
      median survival time were 50.0%, 25.7% and 12.0 months (95%CI: 6.6-17.4). The
      combined therapy group showed higher survival rates than the HAD group (P=0.034).
      Each groups treated with HAD for more than 4 weeks showed higher survival rates
      than those treated for less than 4 weeks, but there was no significant difference
      (P=0.278). In hazard ratio, the combined therapy group showed lower mortality
      rate than the HAD group with statistical significance (P=0.040). CONCLUSIONS: HAD
      could prolong the survival rate of inoperable NSCLC stages over IIIb. HAD is more
      effective when combined with conventional therapy. In the future, more controlled
      clinical trials with larger sample in multi-centers are needed to reevaluate the
      efficacy and safety of HAD.

PMID- 21081040
TI  - [Chemokine receptor 7 induces metastasis of NSCLC via upregulating MMP-9
      expression].
AB  - BACKGROUND: It has been proven that CC chemokine receptor 7 (CCR7) is closely
      related with the lymph node metastasis of non-small cell lung cancer (NSCLC), but
      the mechanism of NSCLC metastasis is not very clear. The aim of this study is to
      investigate the expressions of CCR7 and MMP-9 in NSCLC and the relationship of
      their expressions, and to explore the mechanism of CCR7 promoting NSCLC
      metastasis. METHODS: The expressions of CCR7 and MMP-9 protein were detected in
      90 specimens of human primary NSCLC by immunohistochemical SP method. Human large
      lung cell line BE1 cells were pre-incubated with CCL19 for 24 h; the changes of
      MMP-9 were detected by RT-PCR and Western blot. RESULTS: Immunohistochemistry
      showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells and
      MMP-9 was distributed in cytoplasm of cancer cells. The expressions of CCR7 and
      MMP-9 protein were found to be 70% (63/90) and 65.5% (59/90) in NSCLC,
      respectively. The expressions of CCR7 and MMP-9 protein were closely related to
      the clinical stages (P=0.003, P=0.001) and lymph node metastasis (P=0.004,
      P=0.003) of NSCLC, but there was no correlation with age, gender, histology (P >
      0.05). Furthermore, a significant correlation was found between CCR7 and MMP-9
      (r=0.342, P=0.001). In addition, the expressions of MMP-9 mRNA and protein levels
      were increased in CCL19 pre-incubated group (P < 0.05). CONCLUSIONS: The
      expressions of CCR7 and MMP-9 are significantly associated with NSCLC invasion
      and metastasis. The upregulation of MMP-9 is regulated by CCR7 in NSCLC.

PMID- 21081041
TI  - [A cross-sectional investigation on risk factors of lung cancer for residents
      over 40 years old in Chengdu, Sichuan Province, China].
AB  - BACKGROUND: In the previous studies, we have designed the Self-evaluation Scoring
      Questionnaire for High-risk Individuals of Lung Cancer. In order to make a better
      understanding of the status of risk factors of lung cancer for residents in
      Chengdu, we carried out the investigation from June 2009 to December 2009.
      METHODS: With the stratified random sampling method, eligible residents were
      included and their risk factors of lung cancer were collected with the Self
      evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer.
      RESULTS: According to the criteria of the questionnaire, 21.34% of the population
      were at high risk of lung cancer. The smoking rate for male was 48.58%, higher
      than that of 2.65% for female. About 5.39% of male smokers began smoking before
      15 years old. The average daily tobacco consumption in the most population was
      less than 20 pieces, with a duration between 20 to 40 years. However, there were
      11.34% of all women suffered from passive smoking, and another 15.30% and 5.86%
      of residents were exposed to cooking fumes, minerals or asbestos. As for the
      previous illness history, 0.77%-18.08% of individuals have connective tissue
      diseases, pulmonary tuberculosis, emphysema and others. Finally, 4.91% of
      residents endured the long-term mental depression, and 7.24% had a positive
      family history of tumors. CONCLUSIONS: The status of risk factors for lung cancer
      among residents in Chengdu was not optimistic. It should be paid more attention
      to tobacco control and environmental improvement to improve people's health.

PMID- 21081042
TI  - [A meta analysis of aidi injection plus taxotere and cisplatin in the treatment
      of non-small cell lung cancer].
AB  - BACKGROUND: Compared with chemotherapy, whether aidi injection can improve the
      patient's quality of life is not definite. The aim of this study is to evaluate
      the efficacy and safety of axotere plus eisplatin chemotherapy combining aidi
      injection for patients with non-small cell lung cancer (NSCLC). METHODS: We
      searched relevant randomized controlled trials (RCTs) from Cochrane library,
      Pubmed, EMBASE, CancerLit, VIP, CBM and CNKI etc. The search was finished in
      March 20, 2010. We traced the related references and experts in this field,
      besides we also communicated with other authors to obtain some certain
      information that has not been found. RCTs of aidi injection plus TP versus TP for
      advanced NSCLC were included. We evaluated the quality of these included studies
      and analyzed data by Cochrane Collaboration's RevMan 5.0 software. RESULTS:
      Eleven RCTs involving 800 patients were included. meta analysis results suggested
      that compared with TP chemotherapy alone, the combination had a statistically
      significant benefit in healing efficacy (RR=1.2, 95%CI: 1.10-1.47, P=0.001) and
      improving quality of life (QOL) (RR=1.85, 95%Cl: 1.54-2.21, P < 0.001). Besides,
      the combination also had a statistically significant benefit in myelosuppression,
      white blood cell (WBC)(RR=0.71, 95%CI: 0.57-0.87, P=0.001) and hematoblast
      (RR=0.59, 95%CI: 0.40-0.87, P=0.008) and in reducing the gastroenteric reaction
      (RR=0.75, 95%CI: 0.58-0.98, P=0.03). But the combination had no statistically
      significant benefit in prevention of reducing hemoglobin (Hb) (RR=0.97, 95%CI:
      0.70-1.34, P=0.85), liver function (RR=0.63, 95%CI: 0.09-1.57, P=0.18), kidney
      function (RR=0.42, 95%CI: 0.14-1.24, P=0.12), peripheral neuritis (RR=0.86,
      95%CI: 0.56-1.32, P=0.50), and baldness (RR=0.92, 95%CI: 0.63-1.34, P=0.66).
      CONCLUSIONS: Compared with TP chemotherapy alone, the combination can
      significantly improve the efficiency, QOL and myelosuppression, and reduce
      adverse events.

PMID- 21081043
TI  - [Expression and significance of COX-2 and its transcription factors NFAT3 and c
      Jun in non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Cyclooxygenases (COX), the key enzymes in the
      conversion of arachidonic acid (AA) to prostaglandins (PGs), are involved in
      initiation and progression of cancer. The aim of this study is to explore the
      relationship between the expressions of COX-2 and several transcription factors
      in non-small cell lung cancer. METHODS: Immunohistochemistry was performed to
      assay the expression levels of COX-2, c-Fos, c-Jun and nuclear factor of
      activated T cells 3 (NFAT3) in tissue microarray containing 159 tumor tissues of
      non-small cell lung cancer. RESULTS: The positive rate of COX-2 expression was
      42.8%, and the expression of COX-2 was significantly higher in squamous cell
      carcinoma than that in adenocarcinoma (52.9% vs 31.3%, chi2=7.723, P=0.005). The
      expression of COX-2 was significantly associated with differentiation grade, with
      the lower level in the poorer differentiation grade group (chi2=7.600, P=0.022).
      In this panel of samples, the expression of COX-2 was significantly correlated
      with c-Fos expression (r=0.456, P<0.001) and NFAT3 level (r=0.294, P<0.001). The
      correlation between the expressions of NFAT3 and c-Fos were also observed
      (r=0.231, P=0.003). CONCLUSION: The expression of COX-2 was significantly
      associated with the expressions of transcription factors NFAT3 and c-Fos in
      nonsmall cell lung cancer.

PMID- 21081045
TI  - Retraction of "Effect of bufalin on proliferation and apoptosis of human non
      small cell lung cancer A549 Cell. Zhongguo Fei Ai Za Zhi, 2010, 13(9): 841-845".

PMID- 21081044
TI  - [Expressions and clinical significances of TSLC1 and 4.1B in non-small cell lung
      cancer].
AB  - BACKGROUND: Tumor suppressor in lung cancer-1 (TSLC1) belongs to immunoglobulin
      superfamily of cell adhesion molecule and differentially expressed in
      adenocarcinoma of the lung (4.1B)belongs to NF2/ERM/4.1 protein superfamily. They
      may suppress carcinogenesis via construction of the adjacent cell adhesion
      stability. The aim of this study is to detect the expressions of TSLC1 and 4.1B
      in non-small cell lung cancer and the clinical pathological significances.
      METHODS: The expressions of TSLC1 and 4.1B were detected by RT-PCR in 52 cases of
      non-small cell lung cancer and corresponding adjacent cancer lung tissues
      RESULTS: The expressions of TSLC1 and 4.1B in cancer tissues were significantly
      lower than that in adjacent cancer lung tissues (0.349 +/- 0.008 vs 0.555 +/-
      0.010; 0.209 +/- 0.040 vs 0.721 +/- 0.071) (P < 0.01). The expressions of TSLC1
      and 4.1B showed a significant correlation with cancer differentiation and TNM
      staging (P < 0.05), but not with gender, age and pathological type (P > 0.05).
      The expressions of TSLC1 and 4.1B were positively correlated (r=0.471, P <
      0.001). CONCLUSIONS: Down-regulated expressions of TSLC1 and 4.1B in non-small
      cell lung cancer, both may participate in a cascade of non-small cell lung cancer
      occurrence and development. TSLC1 and 4.1B are promising targets for non-small
      cell lung cancer diagnosis and treatment.

PMID- 21081046
TI  - [Treatment of superior lobe central lung cancer with lung replantation].
AB  - BACKGROUND: Patients suffering from lung cancer often have poor quality of life
      after pneumonectomy. It has clinical significances to preserve maximum lobes of
      the "healthy" lung. The aim of this study is to report the applications of lung
      replantation in treatment of superior lobe central lung cancer. METHODS: Three
      lung cancer cases were included and analysed. The bronchus and margin of lower
      lung lobe were encroached by cancer. Pulmonary artery was invaded and surrounded
      by metastatic lymph node. Complete pneumonectomy, antegrade perfusion and
      retroperfusion with low-potassium dextran (LPD) solution in vitro were performed.
      The retainable lower pulmonary lobe was selected from the isolated lung and
      superior pulmonary vein was replaced with inferior pulmonary veins. The bronchus
      and pulmonary artery were inosculated by turns. RESULTS: The operative cumulative
      time ranged from 220 min to 250 min. The isolated time of lobus inferior
      pulmonary ranged from 120 min to 150 min. The chest tube was pulled out after
      chest X-ray confirmed the reimplant lung full re-expansion. The patients were
      followed up for 4 months to 8 months and accomplished adjuvant chemotherapy for 3
      or 4 periodicities. The patients had a sound quality of life. CONCLUSIONS: Lung
      replantation removing the extensive tumor tissue and retaining the maximum
      pulmonary normal tissue is an useful method for treatment of lung cancer.

PMID- 21081047
TI  - [Analysis of prognostic factors of 80 advanced NSCLC patients treated with
      gefitinib for more than 6 months].
AB  - BACKGROUND: Some clinical predictors can be used to evaluate the efficacy of
      epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy for
      non-small cell lung cancer (NSCLC), including female, East-Asian, non-smoker,
      adenocarcinoma, skin rash, etc. The aim of this study is to explore the prognosis
      of advanced NSCLC patients treated with gefitinib for more than 6 months.
      METHODS: Eighty advanced NSCLC patients treated with gefitinib for more than 6
      months were collected from January, 2005 to March, 2010. The association of their
      clinical characteristics with median progression-free survival time (PFS) was
      analysed. RESULTS: Significantly longer median PFS were found in patients with >
      70 years old, earlier clinical stage (IIIb), non-bone metastasis (27 months vs 12
      months; 32 months vs 12 months; 16 months vs 10 months, P < 0.05). There was no
      significant difference in median PFS between ECOG performance status 0-1 group
      and 2-4 group, between more than 4 cycles of chemotherapy and 1-4 cycles, between
      PFS of chemotherapy > 6 months group and <=6 months group, however, ECOG 0-1
      group and more than 4 cycles of chemotherapy or PFS of chemotherapy > 6 months
      group seemed to have longer median PFS (15 months vs 10 months; 16 months vs 12
      months; 14 months vs 12 months). Compared with no skin rash and grade 0-I rash
      group, the patients with rash or grade >=II rash had longer median PFS (16 months
      vs 13 months, P=0.171; 19 months vs 11 months, P=0.085). The median PFS was not
      related with sex, smoking index, pathological types, metastatic sites except
      bone, treatment strategy, etc (P > 0.05). CONCLUSIONS: For gefitinib treatment,
      longer median PFS is likely to be obtained in patients with > 70 years old,
      earlier clinical stage (IIIb), non-bone metastasis.

PMID- 21081048
TI  - [Bronchial sleeve lobectomy and carinal resection in the treatment of central
      lung cancer: a report of 92 cases].
AB  - BACKGROUND: Surgery is the best treatment for early and middle stage non-small
      cell lung cancer. The aim of this study is to summarize the experience of
      bronchial sleeve mortality lobectomy and carinal resection in the treatment of 92
      patients with central lung cancer from January, 1996 to May, 2010. METHODS: A
      total of 92 patients with central lung cancer underwent pulmonary resection.
      Carinal resection and reconstruction were performed in 14 patients, bronchial
      sleeve resection in 70 patients, and bronchial sleeve combined with pulmonary
      artery sleeve lobectomy in 8 patients. RESULTS: There was no operative mortality.
      The average operation time was 2 hours and 43 minutes. Postoperative
      complications such as pulmonary atelectasis occurred in 6.94% (7/92) of total
      group, and hoarseness in 4.35% (4/92). The 1, 3 and 5 year survival rates were
      80.7%, 59.6% and 31.5%. CONCLUSIONS: Bronchial sleeve lobectomy and double sleeve
      lobectomy are capable of excising pulmonary tumor as much as possible while
      remaining healthy lung tissues. Carinal resection and reconstruction is helpful
      to extend the surgical indication, and increase the chance of successful
      resection.

PMID- 21081050
TI  - [Clinical application and advances in radiofrequency ablation of lung neoplasms].
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide. In recent
      years, radiofrequency ablation (RFA), as a minimally invasive therapy, has been
      increasing utilized as a non-surgical treatment option for patients with primary
      and metastatic lung tumors, and great advances have been achieved. The assessment
      of response after RFA is challenging, and we recommend the use of CT scans, MRI
      scans and PET scans to assess response rate. The purpose of the article is to
      review the principles, experimental background, clinical application and response
      in the treatment of lung neoplasms.

PMID- 21081049
TI  - [Current status of Akt in non-small cell lung cancer].
AB  - Lung cancer is one of the most common malignant tumors in the world, but its
      pathogenesis has still been remaining confusing. As an important protein in
      several signaling pathways, Akt has been identified to play a major role in the
      growth, proliferation, apoptosis and invasion of tumor cells. This paper is to
      review the effects of Akt, together with PDK1, Raf-1 and p70S6K, which are
      upstream and downstream regulatory molecules of Akt, and provide a new basis for
      the pathogenesis of non-small cell lung cancer.

PMID- 21081051
TI  - [Advances of molecular targeted drugs used in maintenance therapy of non-small
      cell lung cancer].
AB  - Radiology is the primary lung cancer screening technique. Whether the mortality
      rate of lung cancer could be markedly reduce by radiological screening was still
      unknown to us. It was suggested that high-risk individuals should take regular
      radiological examinations to detect early lung cancers, followed by suitable
      treatment. In this review, we compared the values of different radiological
      methods in lung cancer screening.

PMID- 21081053
TI  - [A case report of the presence of cavitation in apical segment of right lower
      lobe].

PMID- 21081052
TI  - [Advances of DNA methylation in lung cancer].

PMID- 21081054
TI  - [One case report of male left lung cancer patients with contralateral breast
      metastasis].

PMID- 21081055
TI  - Counting bungarotoxin binding sites of nicotinic acetylcholine receptors in
      mammalian cells with high signal/noise ratios.
AB  - Nicotinic acetylcholine receptors are some of the most studied synaptic proteins;
      however, many questions remain that can only be answered using single molecule
      approaches. Here we report our results from single alpha7 and neuromuscular
      junction type nicotinic acetylcholine receptors in mammalian cell membranes. By
      labeling the receptors with fluorophore-labeled bungarotoxin, we can image
      individual receptors and count the number of bungarotoxin-binding sites in
      receptors expressed in HEK 293 cells. Our results indicate that there are two
      bungarotoxin-binding sites in neuromuscular junction receptors, as expected, and
      five in alpha7 receptors, clarifying previous uncertainty. This demonstrates a
      valuable technique for counting subunits in membrane-bound proteins at the single
      molecule level, with nonspecialized optics and with higher signal/noise ratios
      than previous fluorescent protein-based techniques.

PMID- 21081056
TI  - Minimal Zn(2+) binding site of amyloid-beta.
AB  - Zinc-induced aggregation of amyloid-beta peptide (Abeta) is a hallmark molecular
      feature of Alzheimer's disease. Here we provide direct thermodynamic evidence
      that elucidates the role of the Abeta region 6-14 as the minimal Zn(2+) binding
      site wherein the ion is coordinated by His(6), Glu(11), His(13), and His(14).
      With the help of isothermal titration calorimetry and quantum mechanics/molecular
      mechanics simulations, the region 11-14 was determined as the primary zinc
      recognition site and considered an important drug-target candidate to prevent
      Zn(2+)-induced aggregation of Abeta.

PMID- 21081057
TI  - Measurements of transmembrane potential and magnetic field at the apex of the
      heart.
AB  - We studied the transmembrane potential and magnetic fields from electrical
      activity at the apex of the isolated rabbit heart experimentally using optical
      mapping and superconducting quantum interference device microscopy, and
      theoretically using monodomain and bidomain models. The cardiac apex has a
      complex spiral fiber architecture that plays an important role in the development
      and propagation of action currents during stimulation at the apex. This spiral
      fiber orientation contains both radial electric currents that contribute to the
      electrocardiogram and electrically silent circular currents that cannot be
      detected by the electrocardiogram but are detectable by their magnetic field,
      B(z). In our experiments, the transmembrane potential, V(m), was first measured
      optically and then B(z) was measured with a superconducting quantum interference
      device microscope. Based on a simple model of the spiral structure of the apex,
      V(m) was expected to exhibit circular wave front patterns and B(z) to reflect the
      circular component of the action currents. Although the circular V(m) wave fronts
      were detected, the B(z) maps were not as simple as expected. However, we observed
      a pattern consistent with a tilted axis for the apex spiral fiber geometry. We
      were able to simulate similar patterns in both a monodomain model of a tilted
      stack of rings of dipole current and a bidomain model of a tilted stack of
      spiraled cardiac tissue that was stimulated at the apex. The fact that the
      spatial pattern of the magnetic data was more complex than the simple circles
      observed for V(m) suggests that the magnetic data contain information that cannot
      be found electrically.

PMID- 21081059
TI  - Cell flexibility affects the alignment of model myxobacteria.
AB  - Myxobacteria are social bacteria that exhibit a complex life cycle culminating in
      the development of multicellular fruiting bodies. The alignment of rod-shaped
      myxobacteria cells within populations is crucial for development to proceed. It
      has been suggested that myxobacteria align due to mechanical interactions between
      gliding cells and that cell flexibility facilitates reorientation of cells upon
      mechanical contact. However, these suggestions have not been based on
      experimental or theoretical evidence. Here we created a computational mass-spring
      model of a flexible rod-shaped cell that glides on a substratum periodically
      reversing direction. The model was formulated in terms of experimentally
      measurable mechanical parameters, such as engine force, bending stiffness, and
      drag coefficient. We investigated how cell flexibility and motility engine type
      affected the pattern of cell gliding and the alignment of a population of 500
      mechanically interacting cells. It was found that a flexible cell powered by
      engine force at the rear of the cell, as suggested by the slime extrusion
      hypothesis for myxobacteria motility engine, would not be able to glide in the
      direction of its long axis. A population of rigid reversing cells could indeed
      align due to mechanical interactions between cells, but cell flexibility impaired
      the alignment.

PMID- 21081058
TI  - Diffusion anisotropy in collagen gels and tumors: the effect of fiber network
      orientation.
AB  - The interstitial matrix is comprised of cross-linked collagen fibers, generally
      arranged in nonisotropic orientations. Spatial alignment of matrix components
      within the tissue can affect diffusion patterns of drugs. In this study, we
      developed a methodology for the calculation of diffusion coefficients of
      macromolecules and nanoparticles in collagenous tissues. The tissues are modeled
      as three-dimensional, stochastic, fiber networks with varying degrees of
      alignment. We employed a random walk approach to simulate diffusion and a
      Stokesian dynamics method to account for hydrodynamic hindrance. We performed our
      analysis for four different structures ranging from nearly isotropic to perfectly
      aligned. We showed that the overall diffusion coefficient is not affected by the
      orientation of the network. However, structural anisotropy results in diffusion
      anisotropy, which becomes more significant with increase in the degree of
      alignment, the size of the diffusing particle, and the fiber volume fraction. To
      test our model predictions we performed diffusion measurements in reconstituted
      collagen gels and tumor xenografts. We measured fiber alignment and diffusion
      with second harmonic generation and multiphoton fluorescent recovery after
      photobleaching techniques, respectively. The results showed for the first time in
      tumors that the structure and orientation of collagen fibers in the extracellular
      space leads to diffusion anisotropy.

PMID- 21081060
TI  - Thermodynamic calculations for biochemical transport and reaction processes in
      metabolic networks.
AB  - Thermodynamic analysis of metabolic networks has recently generated increasing
      interest for its ability to add constraints on metabolic network operation, and
      to combine metabolic fluxes and metabolite measurements in a mechanistic manner.
      Concepts for the calculation of the change in Gibbs energy of biochemical
      reactions have long been established. However, a concept for incorporation of
      cross-membrane transport in these calculations is still missing, although the
      theory for calculating thermodynamic properties of transport processes is long
      known. Here, we have developed two equivalent equations to calculate the change
      in Gibbs energy of combined transport and reaction processes based on two
      different ways of treating biochemical thermodynamics. We illustrate the need for
      these equations by showing that in some cases there is a significant difference
      between the proposed correct calculation and using an approximative method. With
      the developed equations, thermodynamic analysis of metabolic networks spanning
      over multiple physical compartments can now be correctly described.

PMID- 21081061
TI  - Spatial dynamics of multistage cell lineages in tissue stratification.
AB  - In developing and self-renewing tissues, terminally differentiated (TD) cell
      types are typically specified through the actions of multistage cell lineages.
      Such lineages commonly include a stem cell and multiple progenitor (transit
      amplifying) cell stages, which ultimately give rise to TD cells. As the tissue
      reaches a tightly controlled steady-state size, cells at different lineage stages
      assume distinct spatial locations within the tissue. Although tissue
      stratification appears to be genetically specified, the underlying mechanisms
      that direct tissue lamination are not yet completely understood. Herein, we use
      modeling and simulations to explore several potential mechanisms that can be
      utilized to create stratification during developmental or regenerative growth in
      general systems and in the model system, the olfactory epithelium of mouse. Our
      results show that tissue stratification can be generated and maintained through
      controlling spatial distribution of diffusive signaling molecules that regulate
      the proliferation of each cell type within the lineage. The ability of feedback
      molecules to stratify a tissue is dependent on a low TD death rate: high death
      rates decrease tissue lamination. Regulation of the cell cycle lengths of stem
      cells by feedback signals can lead to transient accumulation of stem cells near
      the base and apex of tissue.

PMID- 21081062
TI  - Elucidating cytochrome C release from mitochondria: insights from an in silico
      three-dimensional model.
AB  - Mitochondrial regulation of apoptosis depends on the programmed release of
      proapoptotic proteins such as cytochrome c (Cyt c) through the outer
      mitochondrial membrane (OMM). Although a few key processes involved in this
      release have been identified, including the liberation of inner membrane-bound
      Cyt c and formation of diffusible pores on the OMM, other details like the
      transport of Cyt c within complex mitochondrial compartments, e.g., the cristae
      and crista junctions, are not yet fully understood (to our knowledge). In
      particular, a remodeling of the inner mitochondrial membrane accompanying
      apoptosis seen in a few studies, in which crista junctions widen, has been
      hypothesized to be a necessary step in the Cyt c release. Using a three
      dimensional spatial modeling of mitochondrial crista and the crista junction,
      model simulations and analysis illustrated how the interplay among solubilization
      of Cyt c, fast diffusion of Cyt c, and OMM permeabilization gives rise to the
      observed experimental release profile. Importantly, the widening of the crista
      junction was found to have a negligible effect on the transport of free Cyt c
      from cristae. Finally, model simulations showed that increasing the fraction of
      free/loosely-bound Cyt c can sensitize the cell to apoptotic stimuli in a
      threshold manner, which may explain increased sensitivity to cell death
      associated with aging.

PMID- 21081063
TI  - A continuous-binding cross-linker model for passive airway smooth muscle.
AB  - Although the active properties of airway smooth muscle (ASM) have garnered much
      modeling attention, the passive mechanical properties are not as well studied. In
      particular, there are important dynamic effects observed in passive ASM,
      particularly strain-induced fluidization, which have been observed both
      experimentally and in models; however, to date these models have left an
      incomplete picture of the biophysical, mechanistic basis for these behaviors. The
      well-known Huxley cross-bridge model has for many years successfully described
      many of the active behaviors of smooth muscle using sliding filament theory;
      here, we propose to extend this theory to passive biological soft tissue,
      particularly ASM, using as a basis the attachment and detachment of cross-linker
      proteins at a continuum of cross-linker binding sites. The resulting mathematical
      model exhibits strain-induced fluidization, as well as several types of force
      recovery, at the same time suggesting a new mechanistic basis for the behavior.
      The model is validated by comparison to new data from experimental preparations
      of rat tracheal airway smooth muscle. Furthermore, experiments in noncontractile
      tissue show qualitatively similar behavior, suggesting support for the protein
      filament theory as a biomechanical basis for the behavior.

PMID- 21081064
TI  - Correlation resonance generated by coupled enzymatic processing.
AB  - A major challenge for systems biology is to deduce the molecular interactions
      that underlie correlations observed between concentrations of different
      intracellular molecules. Although direct explanations such as coupled
      transcription or direct protein-protein interactions are often considered,
      potential indirect sources of coupling have received much less attention. Here we
      show how correlations can arise generically from a posttranslational coupling
      mechanism involving the processing of multiple protein species by a common
      enzyme. By observing a connection between a stochastic model and a multiclass
      queue, we obtain a closed form expression for the steady-state distribution of
      the numbers of molecules of each protein species. Upon deriving explicit analytic
      expressions for moments and correlations associated with this distribution, we
      discover a striking phenomenon that we call correlation resonance: for small
      dilution rate, correlations peak near the balance-point where the total rate of
      influx of proteins into the system is equal to the maximum processing capacity of
      the enzyme. Given the limited number of many important catalytic molecules, our
      results may lead to new insights into the origin of correlated behavior on a
      global scale.

PMID- 21081065
TI  - Mitotic membrane helps to focus and stabilize the mitotic spindle.
AB  - During mitosis, microtubules (MTs), aided by motors and associated proteins,
      assemble into a mitotic spindle. Recent evidence supports the notion that a
      membranous spindle matrix aids spindle formation; however, the mechanisms by
      which the matrix may contribute to spindle assembly are unknown. To search for a
      mechanism by which the presence of a mitotic membrane might help spindle
      morphology, we built a computational model that explores the interactions between
      these components. We show that an elastic membrane around the mitotic apparatus
      helps to focus MT minus ends and provides a resistive force that acts
      antagonistically to plus-end-directed MT motors such as Eg5.

PMID- 21081066
TI  - Modeling diauxic glycolytic oscillations in yeast.
AB  - Glycolytic oscillations in a stirred suspension of starved yeast cells is an
      excellent model system for studying the dynamics of metabolic switching in living
      systems. In an open-flow system the oscillations can be maintained indefinitely
      at a constant operating point where they can be characterized quantitatively by
      experimental quenching and bifurcation analysis. In this article, we use these
      methods to show that the dynamics of oscillations in a closed system is a simple
      transient version of the open-system dynamics. Thus, easy-setup closed-system
      experiments are also useful for investigations of central metabolism dynamics of
      yeast cells. We have previously proposed a model for the open system comprised of
      the primary fermentative reactions in yeast that quantitatively describes the
      oscillatory dynamics. However, this model fails to describe the transient
      behavior of metabolic switching in a closed-system experiment by feeding the
      yeast suspension with a glucose pulse-notably the initial NADH spike and final
      NADH rise. Another object of this study is to gain insight into the secondary low
      flux metabolic pathways by feeding starved yeast cells with various metabolites.
      Experimental and computational results strongly suggest that regulation of
      acetaldehyde explains the observed behavior. We have extended the original model
      with regulation of pyruvate decarboxylase, a reversible alcohol dehydrogenase,
      and drainage of pyruvate. Using the method of time rescaling in the extended
      model, the description of the transient closed-system experiments is
      significantly improved.

PMID- 21081067
TI  - A biophysical model of electrical activity in human beta-cells.
AB  - Electrical activity in pancreatic beta-cells plays a pivotal role in glucose
      stimulated insulin secretion by coupling metabolism to calcium-triggered
      exocytosis. Mathematical models based on rodent data have helped in understanding
      the mechanisms underlying the electrophysiological patterns observed in
      laboratory animals. However, human beta-cells differ in several aspects, and in
      particular in their electrophysiological characteristics, from rodent beta-cells.
      Hence, from a clinical perspective and to obtain insight into the defects in
      insulin secretion relevant for diabetes mellitus, it is important to study human
      beta-cells. This work presents the first mathematical model of electrical
      activity based entirely on published ion channel characteristics of human beta
      cells. The model reproduces satisfactorily a series of experimentally observed
      patterns in human beta-cells, such as spiking and rapid bursting electrical
      activity, and their response to a range of ion channel antagonists. The
      possibility of Human Ether-a-Go-Go-related- and leak channels as drug targets for
      diabetes treatment is discussed based on model results.

PMID- 21081068
TI  - Drosophila neurons actively regulate axonal tension in vivo.
AB  - Several experiments have shown that mechanical forces significantly influence the
      initiation, growth, and retraction of neurites of cultured neurons. A similar
      role has long been suggested for mechanical forces in vivo, but this hypothesis
      has remained unverified due to the paucity of in vivo studies of neuronal
      mechanical behavior. In this study, we used high-resolution micromechanical force
      sensors to study the mechanical response of motor neurons in live Drosophila
      embryos. Our experiments showed that Drosophila neurons maintained a rest tension
      (1-13 nN) and behaved like viscoelastic solids (i.e., with a linear force
      deformation response followed by force relaxation to steady state) in response to
      sustained stretching. More importantly, when the tension was suddenly diminished
      by a release of the externally applied force, the neurons contracted and actively
      generated force to restore tension, sometimes to a value close to their rest
      tension. In addition, axons that were slackened by displacing the neuromuscular
      junction contracted and became taut in 10-30 min. These observations are
      remarkably similar to results from in vitro studies and suggest that mechanical
      tension may also strongly influence neuronal behavior in vivo.

PMID- 21081069
TI  - Statistics of active transport in Xenopus melanophores cells.
AB  - The transport of cell cargo, such as organelles and protein complexes in the
      cytoplasm, is determined by cooperative action of molecular motors stepping along
      polar cytoskeletal elements. Analysis of transport of individual organelles
      generated useful information about the properties of the motor proteins and
      underlying cytoskeletal elements. In this work, for the first time (to our
      knowledge), we study collective movement of multiple organelles using Xenopus
      melanophores, pigment cells that translocate several thousand of pigment granules
      (melanosomes), spherical organelles of a diameter of ~1 MUm. These cells disperse
      melanosomes in the cytoplasm in response to high cytoplasmic cAMP, while at low
      cAMP melanosomes cluster at the cell center. Obtained results suggest spatial and
      temporal organization, characterized by strong correlations between movement of
      neighboring organelles, with correlation length of ~4 MUm and pair lifetime ~5 s.
      Furthermore, velocity statistics revealed strongly non-Gaussian velocity
      distribution with high velocity tails demonstrating exponential behavior
      suggestive of strong velocity correlations. Depolymerization of vimentin
      intermediate filaments using a dominant-negative vimentin mutant or actin with
      cytochalasin B reduced correlation of behavior of individual particles. Based on
      our analysis, we concluded that steric repulsion is dominant, but both
      intermediate filaments and actin microfilaments are involved in dynamic cross
      linking organelles in the cytoplasm.

PMID- 21081070
TI  - D-enantiomers take a close look at the functioning of a cardiac cationic L-amino
      acid transporter.
AB  - Cationic amino acid transporters are highly selective for L-enantiomers such as L
      arginine (L-Arg). Because of this stereoselectivity, little is known about the
      interaction of these transporters with D-isomers. To study whether these
      compounds can provide information on the molecular mechanism of transport, inward
      currents activated by L-Arg with low apparent affinity were measured in whole
      cell voltage-clamped cardiomyocytes as a function of extracellular L-Arg and D
      Arg concentrations. D-Arg inhibited L-Arg currents in a membrane-potential (V(M))
      dependent competitive manner, indicating the presence of D-Arg binding sites in
      the carrier. Analysis of these steady-state currents showed that L- and D-Arg
      binding reactions dissipate a similar small fraction of the membrane electric
      field. Since D-Arg is not transported, these results suggest that enantiomer
      recognition occurs at conformational transitions that initiate amino acid
      translocation. The V(M) dependence of maximal current levels suggests that inward
      currents arise from the slow outward movement of negative charges in the
      unliganded transporter. Translocation of the L-Arg-bound complex, on the other
      hand, appears to be electroneutral. D-Arg-dependent transient charge movements,
      also detected in these cells, displayed a V(M)-dependent charge distribution and
      kinetics that are consistent with amino acid binding in an ion well in a shallow,
      water-filled extracellular binding pocket.

PMID- 21081071
TI  - Palmitoylation of pulmonary surfactant protein SP-C is critical for its
      functional cooperation with SP-B to sustain compression/expansion dynamics in
      cholesterol-containing surfactant films.
AB  - Recent data suggest that a functional cooperation between surfactant proteins SP
      B and SP-C may be required to sustain a proper compression-expansion dynamics in
      the presence of physiological proportions of cholesterol. SP-C is a dually
      palmitoylated polypeptide of 4.2 kDa, but the role of acylation in SP-C activity
      is not completely understood. In this work we have compared the behavior of
      native palmitoylated SP-C and recombinant nonpalmitoylated versions of SP-C
      produced in bacteria to get a detailed insight into the importance of the
      palmitic chains to optimize interfacial performance of cholesterol-containing
      surfactant films. We found that palmitoylation of SP-C is not essential for the
      protein to promote rapid interfacial adsorption of phospholipids to equilibrium
      surface tensions (~22 mN/m), in the presence or absence of cholesterol. However,
      palmitoylation of SP-C is critical for cholesterol-containing films to reach
      surface tensions <=1 mN/m at the highest compression rates assessed in a captive
      bubble surfactometer, in the presence of SP-B. Interestingly, the ability of SP-C
      to facilitate reinsertion of phospholipids during expansion was not impaired to
      the same extent in the absence of palmitoylation, suggesting the existence of
      palmitoylation-dependent and -independent functions of the protein. We conclude
      that palmitoylation is key for the functional cooperation of SP-C with SP-B that
      enables cholesterol-containing surfactant films to reach very low tensions under
      compression, which could be particularly important in the design of clinical
      surfactants destined to replacement therapies in pathologies such as acute
      respiratory distress syndrome.

PMID- 21081072
TI  - Tensile forces and shape entropy explain observed crista structure in
      mitochondria.
AB  - We present a model from which the observed morphology of the inner mitochondrial
      membrane can be inferred as minimizing the system's free energy. In addition to
      the usual energetic terms for bending, surface area, and pressure difference, our
      free energy includes terms for tension that we hypothesize to be exerted by
      proteins and for an entropic contribution due to many dimensions worth of shapes
      available at a given energy. We also present measurements of the structural
      features of mitochondria in HeLa cells and mouse embryonic fibroblasts using
      three-dimensional electron tomography. Such tomograms reveal that the inner
      membrane self-assembles into a complex structure that contains both tubular and
      flat lamellar crista components. This structure, which contains one matrix
      compartment, is believed to be essential to the proper functioning of
      mitochondria as the powerhouse of the cell. Interpreting the measurements in
      terms of the model, we find that tensile forces of ~20 pN would stabilize a
      stress-induced coexistence of tubular and flat lamellar cristae phases. The model
      also predicts a pressure difference of -0.036 +/- 0.004 atm (pressure higher in
      the matrix) and a surface tension equal to 0.09 +/- 0.04 pN/nm.

PMID- 21081073
TI  - Perfringolysin O association with ordered lipid domains: implications for
      transmembrane protein raft affinity.
AB  - Upon interaction with cholesterol, perfringolysin O (PFO) inserts into membranes
      and forms a rigid transmembrane (TM) beta-barrel. PFO is believed to interact
      with liquid ordered lipid domains (lipid rafts). Because the origin of TM protein
      affinity for rafts is poorly understood, we investigated PFO raft affinity in
      vesicles having coexisting ordered and disordered lipid domains. Fluorescence
      resonance energy transfer (FRET) from PFO Trp to domain-localized acceptors
      indicated that PFO generally has a raft affinity between that of LW peptide (low
      raft affinity) and cholera toxin B (high raft affinity) in vesicles containing
      ordered domains rich in brain sphingomyelin or distearoylphosphatidylcholine.
      FRET also showed that ceramide, which increases exposure of cholesterol to water
      and thus displaces it from rafts, does not displace PFO from ordered domains.
      This can be explained by shielding of PFO-bound cholesterol from water. Finally,
      FRET showed that PFO affinity for ordered domains was higher in its non-TM
      (prepore) form than in its TM form, demonstrating that the TM portion of PFO
      interacts unfavorably with rafts. Microscopy studies in giant unilamellar
      vesicles confirmed that PFO exhibits intermediate raft affinity, and showed that
      TM PFO (but not non-TM PFO) concentrated at the edges of liquid ordered domains.
      These studies suggest that a combination of binding to raft-associating molecules
      and having a rigid TM structure that is unable to pack well in a highly ordered
      lipid environment can control TM protein domain localization. To accommodate
      these constraints, raft-associated TM proteins in cells may tend to locate within
      liquid disordered shells encapsulated within ordered domains.

PMID- 21081074
TI  - A new method for measuring edge tensions and stability of lipid bilayers: effect
      of membrane composition.
AB  - We report a novel and facile method for measuring edge tensions of lipid
      membranes. The approach is based on electroporation of giant unilamellar vesicles
      and analysis of the pore closure dynamics. We applied this method to evaluate the
      edge tension in membranes with four different compositions: egg
      phosphatidylcholine (eggPC), dioleoylphosphatidylcholine (DOPC), and mixtures of
      DOPC with cholesterol and dioleoylphosphatidylethanolamine. Our data confirm
      previous results for eggPC and DOPC. The addition of 17 mol % cholesterol to the
      DOPC membrane causes an increase in the membrane edge tension. On the contrary,
      when the same fraction of dioleoylphosphatidylethanolamine is added to the
      membrane, a decrease in the edge tension is observed, which is an unexpected
      result considering the inverted-cone shape geometry of the molecule. It is
      presumed that interlipid hydrogen bonding is the origin of this behavior.
      Furthermore, cholesterol was found to lower the lysis tension of DOPC bilayers.
      This behavior differs from that observed on bilayers made of
      stearoyloleoylphosphatidylcholine, suggesting that cholesterol influences the
      membrane mechanical stability in a lipid-specific manner.

PMID- 21081075
TI  - Tectorial membrane material properties in Tecta(Y)(1870C/+) heterozygous mice.
AB  - The solid component of the tectorial membrane (TM) is a porous matrix made up of
      the radial collagen fibers and the striated sheet matrix. The striated sheet
      matrix is believed to contribute to shear impedance in both the radial and
      longitudinal directions, but the molecular mechanisms involved have not been
      determined. A missense mutation in Tecta, a gene that encodes for the alpha
      tectorin protein in the striated sheet matrix, causes a 60-dB threshold shift in
      mice with relatively little reduction in outer hair cell amplification. Here, we
      show that this threshold shift is coupled to changes in shear impedance, response
      to osmotic pressure, and concentration of fixed charge of the TM. In
      Tecta(Y)(1870C/+) mice, the tectorin content of the TM was reduced, as was the
      content of glycoconjugates reacting with the lectin wheat germ agglutinin. Charge
      measurements showed a decrease in fixed charge concentration from -6.4+/-1.4
      mmol/L in wild-types to -2.1+/-0.7 mmol/L in Tecta(Y)(1870C/+) TMs. TMs from
      Tecta(Y)(1870C/+) mice showed little volume change in response to osmotic
      pressure compared to those of wild-type mice. The magnitude of both radial and
      longitudinal TM shear impedance was reduced by 10+/-1.6 dB in Tecta(Y)(1870C/+)
      mice. However, the phase of shear impedance was unchanged. These changes are
      consistent with an increase in the porosity of the TM and a corresponding
      decrease of the solid fraction. Mechanisms by which these changes can affect the
      coupling between outer and inner hair cells are discussed.

PMID- 21081076
TI  - Dynamic structure of bombolitin II bound to lipid bilayers as revealed by solid
      state NMR and molecular-dynamics simulation.
AB  - Bombolitin II (BLT2) is one of the hemolytic heptadecapeptides originally
      isolated from the venom of a bumblebee. Structure and orientation of BLT2 bound
      to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes were determined
      by solid-state (31)P and (13)C NMR spectroscopy. (31)P NMR spectra showed that
      BLT2-DPPC membranes were disrupted into small particles below the gel-to-liquid
      crystalline phase transition temperature (T(c)) and fused to form a magnetically
      oriented vesicle system where the membrane surface is parallel to the magnetic
      fields above the T(c). (13)C NMR spectra of site-specifically (13)C-labeled BLT2
      at the carbonyl carbons were observed and the chemical shift anisotropies were
      analyzed to determine the dynamic structure of BLT2 bound to the magnetically
      oriented vesicle system. It was revealed that the membrane-bound BLT2 adopted an
      alpha-helical structure, rotating around the membrane normal with the tilt angle
      of the helical axis at 33 degrees . Interatomic distances obtained from
      rotational-echo double-resonance experiments further showed that BLT2 adopted a
      straight alpha-helical structure. Molecular dynamics simulation performed in the
      BLT2-DPPC membrane system showed that the BLT2 formed a straight alpha-helix and
      that the C-terminus was inserted into the membrane. The alpha-helical axis is
      tilted 30 degrees  to the membrane normal, which is almost the same as the value
      obtained from solid-state NMR. These results suggest that the membrane disruption
      induced by BLT2 is attributed to insertion of BLT2 into the lipid bilayers.

PMID- 21081077
TI  - Combined and independent action of proteins SP-B and SP-C in the surface behavior
      and mechanical stability of pulmonary surfactant films.
AB  - The hydrophobic proteins SP-B and SP-C are essential for pulmonary surfactant
      function, even though they are a relatively minor component (<2% of surfactant
      dry mass). Despite countless studies, their specific differential action and
      their possible concerted role to optimize the surface properties of surfactant
      films have not been completely elucidated. Under conditions kept as
      physiologically relevant as possible, we tested the surface activity and
      mechanical stability of several surfactant films of varying protein composition
      in vitro using a captive bubble surfactometer and a novel (to our knowledge)
      stability test. We found that in the naturally derived surfactant lipid mixtures,
      surfactant protein SP-B promoted film formation and reextension to lower surface
      tensions than SP-C, and in particular played a vital role in sustaining film
      stability at the most compressed states, whereas SP-C produced no stabilization.
      Preparations containing both proteins together revealed a slight combined effect
      in enhancing film formation. These results provide a qualitative and quantitative
      framework for the development of future synthetic therapeutic surfactants, and
      illustrate the crucial need to include SP-B or an efficient SP-B analog for
      optimal function.

PMID- 21081078
TI  - Effect of sphingomyelin headgroup size on molecular properties and interactions
      with cholesterol.
AB  - Sphingomyelins (SMs) and sterols are important constituents of the plasma
      membrane and have also been identified as major lipid components in membrane
      rafts. Using SM analogs with decreasing headgroup methylation, we systemically
      analyzed the effect of headgroup size on membrane properties and interactions
      with cholesterol. An increase in headgroup size resulted in a decrease in the
      main phase transition. Atom-scale molecular-dynamics simulations were in
      agreement with the fluorescence anisotropy experiments, showing that molecular
      areas increased and acyl chain order decreased with increasing headgroup size.
      Furthermore, the transition temperatures were constantly higher for SM headgroup
      analogs compared to corresponding phosphatidylcholine headgroup analogs. The
      sterol affinity for phospholipid bilayers was assessed using a sterol
      partitioning assay and an increased headgroup size increased sterol affinity for
      the bilayer, with a higher sterol affinity for SM analogs as compared to
      phosphatidylcholine analogs. Moreover, the size of the headgroup affected the
      formation and composition of cholesterol-containing ordered domains. Palmitoyl-SM
      (the largest headgroup) seemed to attract more cholesterol into ordered domains
      than the other SM analogs with smaller headgroups. The ordering and condensing
      effect of cholesterol on membrane lipids was also largest for palmitoyl-SM as
      compared to the smaller SM analogs. The results show that the size of the SM
      headgroup is crucially important for SM-SM and SM-sterol interactions. Our
      results further emphasize that interfacial electrostatic interactions are
      important for stabilizing cholesterol interactions with SMs.

PMID- 21081079
TI  - Comparison of three ternary lipid bilayer mixtures: FRET and ESR reveal
      nanodomains.
AB  - Phase diagrams of ternary lipid mixtures containing cholesterol have provided
      valuable insight into cell membrane behaviors, especially by describing regions
      of coexisting liquid-disordered (Ld) and liquid-ordered (Lo) phases. Fluorescence
      microscopy imaging of giant unilamellar vesicles has greatly assisted the
      determination of phase behavior in these systems. However, the requirement for
      optically resolved Ld + Lo domains can lead to the incorrect inference that in
      lipid-only mixtures, Ld + Lo domain coexistence generally shows macroscopic
      domains. Here we show this inference is incorrect for the low melting temperature
      phosphatidylcholines abundant in mammalian plasma membranes. By use of high
      compositional resolution Forster resonance energy transfer measurements, together
      with electron spin resonance data and spectral simulation, we find that ternary
      mixtures of DSPC and cholesterol together with either POPC or SOPC, do indeed
      have regions of Ld + Lo coexistence. However, phase domains are much smaller than
      the optical resolution limit, likely on the order of the Forster distance for
      energy transfer (R(0), ~2-8 nm).

PMID- 21081080
TI  - Compressibilities and volume fluctuations of archaeal tetraether liposomes.
AB  - Bipolar tetraether lipids (BTLs) are abundant in crenarchaeota, which thrive in
      both thermophilic and nonthermophilic environments, with wide-ranging growth
      temperatures (4-108 degrees C). BTL liposomes can serve as membrane models to
      explore the role of BTLs in the thermal stability of the plasma membrane of
      crenarchaeota. In this study, we focus on the liposomes made of the polar lipid
      fraction E (PLFE). PLFE is one of the main BTLs isolated from the
      thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. Using molecular
      acoustics (ultrasound velocimetry and densimetry), pressure perturbation
      calorimetry, and differential scanning calorimetry, we have determined partial
      specific adiabatic and isothermal compressibility, their respective
      compressibility coefficients, partial specific volume, and relative volume
      fluctuations of PLFE large unilamellar vesicles (LUVs) over a wide range of
      temperatures (20-85 degrees C). The results are compared with those obtained from
      liposomes made of dipalmitoyl-L-alpha-phosphatidylcholine (DPPC), a conventional
      monopolar diester lipid. We found that, in the entire temperature range examined,
      compressibilities of PLFE LUVs are low, comparable to those found in gel state of
      DPPC. Relative volume fluctuations of PLFE LUVs at any given temperature examined
      are 1.6-2.2 times more damped than those found in DPPC LUVs. Both
      compressibilities and relative volume fluctuations in PLFE LUVs are much less
      temperature-sensitive than those in DPPC liposomes. The isothermal
      compressibility coefficient (beta(T)(lipid)) of PLFE LUVs changes from 3.59 * 10(
      10) Pa(-1) at 25 degrees C to 4.08 * 10(-10) Pa(-1) at 78 degrees C. Volume
      fluctuations of PLFE LUVs change only 0.25% from 30 degrees C to 80 degrees C.
      The highly damped volume fluctuations and their low temperature sensitivity, echo
      that PLFE liposomes are rigid and tightly packed. To our knowledge, the data
      provide a deeper understanding of lipid packing in PLFE liposomes than has been
      previously reported, as well as a molecular explanation for the low solute
      permeation and limited membrane lateral motion. The obtained results may help to
      establish new strategies for rational design of stable BTL-based liposomes for
      drug/vaccine delivery.

PMID- 21081083
TI  - A stochastic model for chemotaxis based on the ordered extension of pseudopods.
AB  - Many amoeboid cells move by extending pseudopods. Here I present a new stochastic
      model for chemotaxis that is based on pseudopod extensions by Dictyostelium
      cells. In the absence of external cues, pseudopod extension is highly ordered
      with two types of pseudopods: de novo formation of a pseudopod at the cell body
      in random directions, and alternating right/left splitting of an existing
      pseudopod that leads to a persistent zig-zag trajectory. We measured the
      directional probabilities of the extension of splitting and de novo pseudopods in
      chemoattractant gradients with different steepness. Very shallow cAMP gradients
      can bias the direction of splitting pseudopods, but the bias is not perfect.
      Orientation of de novo pseudopods require much steeper cAMP gradients and can be
      more precise. These measured probabilities of pseudopod directions were used to
      obtain an analytical model for chemotaxis of cell populations. Measured
      chemotaxis of wild-type cells and mutants with specific defects in these
      stochastic pseudopod properties are similar to predictions of the model. These
      results show that combining splitting and de novo pseudopods is a very effective
      way for cells to obtain very high sensitivity to stable gradient and still be
      responsive to changes in the direction of the gradient.

PMID- 21081082
TI  - Nucleotide-dependent shape changes in the reverse direction motor, myosin VI.
AB  - We have studied the shape of myosin VI, the actin minus-end directed motor, by
      negative stain and metal shadow electron microscopy. Single particle processing
      was used to make two-dimensional averages of the stain images, which greatly
      increases the clarity and allows detailed comparisons with crystal structures. A
      total of 169,964 particle images were obtained from two different constructs in
      six different states (four nucleotide states and with and without Ca(2+)). The
      shape of truncated apo myosin VI was very similar to the apo crystal structure,
      with the lever arm bent strongly backward and around the motor domain. In the
      full-length molecule, the C-terminal part of the tail has an additional bend
      taking it back across the motor domain, which may reflect a regulated state.
      Addition of ATP, ADP, or ATP-gammaS resulted in a large change, straightening the
      molecule from the bent shape and swinging the lever by ~140 degrees . Although
      these nucleotides would not be expected to produce the pre-powerstroke state,
      myosin VI in their presence was most similar to the truncated crystal structure
      with bound ADP-VO(4), which is thought to show the pre-powerstroke shape. The
      nucleotide data were therefore substantially different from expectation based on
      crystal structures. The full-length molecule was almost completely monomeric;
      only ~1% were dimers, joined through the ends of the tail. Addition of calcium
      ions appeared to result in release of the second calmodulin light chain. In
      negatively stained molecules there was little indication of extended alpha
      helical structure in the tail, but molecules viewed by metal shadowing had a tail
      ~3* longer, 29 vs. 9 nm, part of which is likely to be a single alpha-helix.

PMID- 21081081
TI  - Multiple cellular proteins modulate the dynamics of K-ras association with the
      plasma membrane.
AB  - Although specific proteins have been identified that regulate the membrane
      association and facilitate intracellular transport of prenylated Rho- and Rab
      family proteins, it is not known whether cellular proteins fulfill similar roles
      for other prenylated species, such as Ras-family proteins. We used a previously
      described method to evaluate how several cellular proteins, previously identified
      as potential binding partners (but not effectors) of K-ras4B, influence the
      dynamics of K-ras association with the plasma membrane. Overexpression of either
      PDEdelta or PRA1 enhances, whereas knockdown of either protein reduces, the rate
      of dissociation of K-ras from the plasma membrane. Inhibition of calmodulin
      likewise reduces the rate of K-ras dissociation from the plasma membrane, in this
      case in a manner specific for the activated form of K-ras. By contrast, galectin
      3 specifically reduces the rate of plasma membrane dissociation of activated K
      ras, an effect that is blocked by the K-ras antagonist farnesylthiosalicylic acid
      (salirasib). Multiple cellular proteins thus control the dynamics of membrane
      association and intercompartmental movement of K-ras to an important degree even
      under basal cellular conditions.

PMID- 21081084
TI  - Twist propagation in dinucleosome arrays.
AB  - We present a Monte Carlo simulation study of the distribution and propagation of
      twist from one DNA linker to another for a two-nucleosome array subjected to
      externally applied twist. A mesoscopic model of the array that incorporates
      nucleosome geometry along with the bending and twisting mechanics of the linkers
      is employed and external twist is applied in stepwise increments to mimic
      quasistatic twisting of chromatin fibers. Simulation results reveal that the
      magnitude and sign of the imposed and induced twist on contiguous linkers depend
      strongly on their relative orientation. Remarkably, the relative direction of the
      induced and applied twist can become inverted for a subset of linker orientations
      a phenomenon we refer to as "twist inversion". We characterize the twist
      inversion, as a function of relative linker orientation, in a phase diagram and
      explain its key features using a simple model based on the geometry of the
      nucleosome/linker complex. In addition to twist inversion, our simulations reveal
      "nucleosome flipping", whereby nucleosomes may undergo sudden flipping in
      response to applied twist, causing a rapid bending of the linker and a
      significant change in the overall twist and writhe of the array. Our findings
      shed light on the underlying mechanisms by which torsional stresses impact
      chromatin organization.

PMID- 21081087
TI  - Ion accumulation in a protein nanocage: finding noisy temporal sequences using a
      genetic algorithm.
AB  - Many pathogenic bacteria are able to survive attack by the host's immune system
      because of antioxidant systems that mitigate the effects of reactive oxygen
      species. Dps is a hollow 12-subunit protein nanocage that prevents oxidative
      damage by oxidizing and sequestering intracellular Fe(2+); the resulting Fe(3+)
      forms an iron oxyhydroxide nanoparticle in the cage interior. Charged sites on
      the protein nanocage create an electrostatic gradient that guides ions through
      well-defined pores that connect the cage interior with the surrounding solution
      and toward nucleation sites on the cage interior. In this study, we use all-atom
      molecular dynamics to simulate the motion of simple cations into the dodecameric
      cage formed by the Dps protein from Listeria monocytogenes. Ion trajectories are
      analyzed by using a novel, to our knowledge, genetic algorithm to determine the
      temporal sequence of ion-protein interactions. Ions enter Dps through well
      defined pores at the ferritinlike C(3) axes, with negatively-charged residues on
      the outside of the cage forming a fairly well-defined entrance pathway. This
      method of trajectory analysis may be broadly applicable in situations where the
      spatial localization of ions or other small molecules is electrostatically driven
      by a biomolecule.

PMID- 21081085
TI  - pK(a) values for the unfolded state under native conditions explain the pH
      dependent stability of PGB1.
AB  - Understanding the role of electrostatics in protein stability requires knowledge
      of these interactions in both the folded and unfolded states. Electrostatic
      interactions can be probed experimentally by characterizing ionization equilibria
      of titrating groups, parameterized as pK(a) values. However, pK(a) values of the
      unfolded state are rarely accessible under native conditions, where the unfolded
      state has a very low population. Here, we report pK(a) values under nondenaturing
      conditions for two unfolded fragments of the protein G B1 domain that mimic the
      unfolded state of the intact protein. pK(a) values were determined for carboxyl
      groups by monitoring their pH-dependent (13)C chemical shifts. Monte Carlo
      simulations using a Gaussian chain model provide corrections for changes in
      electrostatic interactions that arise from fragmentation of the protein. Most
      pK(a) values for the unfolded state agree well with model values, but some
      residues show significant perturbations that can be rationalized by local
      electrostatic interactions. The pH-dependent stability was calculated from the
      experimental pK(a) values of the folded and unfolded states and compared to
      experimental stability data. The use of experimental pK(a) values for the
      unfolded state results in significantly improved agreement with experimental
      data, as compared to calculations based on model data alone.

PMID- 21081086
TI  - Folding network of villin headpiece subdomain.
AB  - Protein folding is a complex multidimensional process that is difficult to
      illustrate by the traditional analyses based on one- or two-dimensional profiles.
      Analyses based on transition networks have become an alternative approach that
      has the potential to reveal detailed features of protein folding dynamics.
      However, due to the lack of successful reversible folding of proteins from
      conventional molecular-dynamics simulations, this approach has rarely been
      utilized. Here, we analyzed the folding network from several 10 MUs conventional
      molecular-dynamics reversible folding trajectories of villin headpiece subdomain
      (HP35). The folding network revealed more complexity than the traditional two
      dimensional map and demonstrated a variety of conformations in the unfolded
      state, intermediate states, and the native state. Of note, deep enthalpic traps
      at the unfolded state were observed on the folding landscape. Furthermore, in
      contrast to the clear separation of the native state and the primary intermediate
      state shown on the two-dimensional map, the two states were mingled on the
      folding network, and prevalent interstate transitions were observed between these
      two states. A more complete picture of the folding mechanism of HP35 emerged when
      the traditional and network analyses were considered together.

PMID- 21081088
TI  - Multibody effects in ion binding and selectivity.
AB  - Selective binding of ions to biomolecules plays a vital role in numerous
      biological processes. To understand the specific role of induced effects in
      selective ion binding, we use quantum chemical and pairwise-additive force-field
      simulations to study Na(+) and K(+) binding to various small molecules
      representative of ion binding functional groups in biomolecules. These studies
      indicate that electronic polarization significantly contributes to both absolute
      and relative ion-binding affinities. Furthermore, this contribution depends on
      both the number and the specific chemistries of the coordinating molecules, thus
      highlighting the complexity of ion-ligand interactions. Specifically, multibody
      interactions reduce as well as enhance the dipole moments of the ion-coordinating
      molecules, thereby affecting observables like coordination number distributions
      of ions. The differential polarization induced in molecules coordinating these
      two equivalently charged, but different-sized, ions also depends upon the number
      of coordinating molecules, showing the importance of multibody effects in
      distinguishing these ions thermodynamically. Because even small differences in
      ionic radii (0.4 A for Na(+) and K(+)) produce differential polarization trends
      critical to distinguishing ions thermodynamically, it is likely that polarization
      plays an important role in thermodynamically distinguishing other ions and
      charged chemical and biological functional groups.

PMID- 21081089
TI  - Two latent and two hyperstable polymeric forms of human neuroserpin.
AB  - Human neuroserpin (hNS) is a serine protease inhibitor that belongs to the serpin
      superfamily and is expressed in nervous tissues. The serpin fold is generally
      characterized by a long exposed loop, termed the reactive center loop, that acts
      as bait for the target protease. Intramolecular insertion of the reactive center
      loop into the main serpin beta-sheet leads to the serpin latent form. As with
      other known serpins, hNS pathological mutants have been shown to accumulate as
      polymers composed of quasi-native protein molecules. Although hNS polymerization
      has been intensely studied, a general agreement about serpin polymer organization
      is still lacking. Here we report a biophysical characterization of native hNS
      that is shown to undergo two distinct conformational transitions, at 55 degrees C
      and 85 degrees C, both leading to distinct latent and polymeric species. The
      latent and polymer hNS forms obtained at 45 degrees C and 85 degrees C differ in
      their chemical and thermal stabilities; furthermore, the hNS polymers also differ
      in size and morphology. Finally, the 85 degrees C polymer shows a higher content
      of intermolecular beta-sheet interactions than the 45 degrees C polymer.
      Together, these results suggest a more complex conformational scenario than was
      previously envisioned, and, in a general context, may help reconcile the current
      contrasting views on serpin polymerization.

PMID- 21081090
TI  - Functional modes and residue flexibility control the anisotropic response of
      guanylate kinase to mechanical stress.
AB  - The coupling between the mechanical properties of enzymes and their biological
      activity is a well-established feature that has been the object of numerous
      experimental and theoretical works. In particular, recent experiments show that
      enzymatic function can be modulated anisotropically by mechanical stress. We
      study such phenomena using a method for investigating local flexibility on the
      residue scale that combines a reduced protein representation with Brownian
      dynamics simulations. We performed calculations on the enzyme guanylate kinase to
      study its mechanical response when submitted to anisotropic deformations. The
      resulting modifications of the protein's rigidity profile can be related to the
      changes in substrate binding affinity observed experimentally. Further analysis
      of the principal components of motion of the trajectories shows how the
      application of a mechanical constraint on the protein can disrupt its dynamics,
      thus leading to a decrease of the enzyme's catalytic rate. Eventually, a
      systematic probe of the protein surface led to the prediction of potential
      hotspots where the application of an external constraint would produce a large
      functional response both from the mechanical and dynamical points of view. Such
      enzyme-engineering approaches open the possibility to tune catalytic function by
      varying selected external forces.

PMID- 21081091
TI  - On the roles of substrate binding and hinge unfolding in conformational changes
      of adenylate kinase.
AB  - We characterized the conformational change of adenylate kinase (AK) between open
      and closed forms by conducting five all-atom molecular-dynamics simulations, each
      of 100 ns duration. Different initial structures and substrate binding
      configurations were used to probe the pathways of AK conformational change in
      explicit solvent, and no bias potential was applied. A complete closed-to-open
      and a partial open-to-closed transition were observed, demonstrating the direct
      impact of substrate-mediated interactions on shifting protein conformation. The
      sampled configurations suggest two possible pathways for connecting the open and
      closed structures of AK, affirming the prediction made based on available x-ray
      structures and earlier works of coarse-grained modeling. The trajectories of the
      all-atom molecular-dynamics simulations revealed the complexity of protein
      dynamics and the coupling between different domains during conformational change.
      Calculations of solvent density and density fluctuations surrounding AK did not
      show prominent variation during the transition between closed and open forms.
      Finally, we characterized the effects of local unfolding of an important hinge
      near Pro(177) on the closed-to-open transition of AK and identified a novel
      mechanism by which hinge unfolding modulates protein conformational change. The
      local unfolding of Pro(177) hinge induces alternative tertiary contacts that
      stabilize the closed structure and prevent the opening transition.

PMID- 21081092
TI  - High-pressure SAXS study of folded and unfolded ensembles of proteins.
AB  - A structural interpretation of the thermodynamic stability of proteins requires
      an understanding of the structural properties of the unfolded state. High
      pressure small-angle x-ray scattering was used to measure the effects of
      temperature, pressure, denaturants, and stabilizing osmolytes on the radii of
      gyration of folded and unfolded state ensembles of staphylococcal nuclease. A set
      of variants with the internal Val-66 replaced with Ala, Tyr, or Arg was used to
      examine how changes in the volume and polarity of an internal microcavity affect
      the dimensions of the native state and the pressure sensitivity of the ensemble.
      The unfolded state ensembles achieved for these proteins with high pressure were
      more compact than those achieved at high temperature, and were all very sensitive
      to the presence of urea and glycerol. Substitutions at the hydrophobic core
      detectably altered the conformation of the protein, even in the folded state. The
      introduction of a charged residue, such as Arg, inside the hydrophobic interior
      of a protein could dramatically alter the structural properties, even those of
      the unfolded state. The data suggest that a charge at an internal position can
      interfere with the formation of transient hydrophobic clusters in the unfolded
      state, and ensure that the pressure-unfolded form of a protein occupies the
      maximum volume possible. Only at high temperatures does the radius of gyration of
      the unfolded state ensemble approach the value for a statistical random coil.

PMID- 21081093
TI  - All-atom models of the membrane-spanning domain of HIV-1 gp41 from metadynamics.
AB  - The 27-residue membrane-spanning domain (MSD) of the HIV-1 glycoprotein gp41
      bears conserved sequence elements crucial to the biological function of the
      virus, in particular a conserved GXXXG motif and a midspan arginine. However,
      structure-based explanations for the roles of these and other MSD features remain
      unclear. Using molecular dynamics and metadynamics calculations of an all-atom,
      explicit solvent, and membrane-anchored model, we study the conformational
      variability of the HIV-1 gp41 MSD. We find that the MSD peptide assumes a stable
      tilted alpha-helical conformation in the membrane. However, when the side chain
      of the midspan Arg (694) "snorkels" to the outer leaflet of the viral membrane,
      the MSD assumes a metastable conformation where the highly-conserved N-terminal
      core (between Lys(681) and Arg(694) and containing the GXXXG motif) unfolds. In
      contrast, when the Arg(694) side chain snorkels to the inner leaflet, the MSD
      peptide assumes a metastable conformation consistent with experimental
      observations where the peptide kinks at Phe(697) to facilitate Arg(694)
      snorkeling. Both of these models suggest specific ways that gp41 may destabilize
      viral membrane, priming the virus for fusion with a target cell.

PMID- 21081094
TI  - Discovery of entry inhibitors for HIV-1 via a new de novo protein design
      framework.
AB  - A new (to our knowledge) de novo design framework with a ranking metric based on
      approximate binding affinity calculations is introduced and applied to the
      discovery of what we believe are novel HIV-1 entry inhibitors. The framework
      consists of two stages: a sequence selection stage and a validation stage. The
      sequence selection stage produces a rank-ordered list of amino-acid sequences by
      solving an integer programming sequence selection model. The validation stage
      consists of fold specificity and approximate binding affinity calculations. The
      designed peptidic inhibitors are 12-amino-acids-long and target the hydrophobic
      core of gp41. A number of the best-predicted sequences were synthesized and their
      inhibition of HIV-1 was tested in cell culture. All peptides examined showed
      inhibitory activity when compared with no drug present, and the novel peptide
      sequences outperformed the native template sequence used for the design. The best
      sequence showed micromolar inhibition, which is a 3-15-fold improvement over the
      native sequence, depending on the donor. In addition, the best sequence equally
      inhibited wild-type and Enfuvirtide-resistant virus strains.

PMID- 21081095
TI  - Comparative analysis of RNA/protein dynamics for the arginine-rich-binding motif
      and zinc-finger-binding motif proteins encoded by HIV-1.
AB  - We report a comparative study in which a single-molecule fluorescence resonance
      energy transfer approach was used to examine how the binding of two families of
      HIV-1 viral proteins to viral RNA hairpins locally changes the RNA secondary
      structures. The single-molecule fluorescence resonance energy transfer results
      indicate that the zinc finger protein (nucleocapsid) locally melts the TAR RNA
      and RRE-IIB RNA hairpins, whereas arginine-rich motif proteins (Tat and Rev) may
      strengthen the hairpin structures through specific binding interactions.
      Competition experiments show that Tat and Rev can effectively inhibit the
      nucleocapsid-chaperoned annealing of complementary DNA oligonucleotides to the
      TAR and RRE-IIB RNA hairpins, respectively. The competition binding data
      presented here suggest that the specific nucleic acid binding interactions of Tat
      and Rev can effectively compete with the general nucleic acid binding/chaperone
      functions of the nucleocapsid protein, and thus may in principle help regulate
      critical events during the HIV life cycle.

PMID- 21081096
TI  - Modeling DNA polymerase MU motions: subtle transitions before chemistry.
AB  - To investigate whether an open-to-closed transition before the chemical step and
      induced-fit mechanism exist in DNA polymerase MU (pol MU), we analyze a series of
      molecular-dynamics simulations with and without the incoming nucleotide in
      various forms, including mutant systems, based on pol MU's crystal ternary
      structure. Our simulations capture no significant large-scale motion in either
      the DNA or the protein domains of pol MU. However, subtle residue motions can be
      distinguished, specifically of His(329) and Asp(330) to assemble in pol MU's
      active site, and of Gln(440) and Glu(443) to help accommodate the incoming
      nucleotide. Mutant simulations capture a DNA frameshift pairing and indicate the
      importance of Arg(444) and Arg(447) in stacking with the DNA template, and of
      Arg(448) and Gln(440) in helping to stabilize the position of both the DNA
      template and the incoming nucleotide. Although limited sampling in the molecular
      dynamics simulations cannot be ruled out, our studies suggest an absence of a
      large-scale motion in pol MU. Together with the known crystallization
      difficulties of capturing the open form of pol MU, our studies also raise the
      possibility that a well-defined open form may not exist. Moreover, we suggest
      that residues Arg(448) and Gln(440) may be crucial for preventing insertion
      frameshift errors in pol MU.

PMID- 21081097
TI  - Activation of nanoscale allosteric protein domain motion revealed by neutron spin
      echo spectroscopy.
AB  - NHERF1 is a multidomain scaffolding protein that assembles signaling complexes,
      and regulates the cell surface expression and endocytic recycling of a variety of
      membrane proteins. The ability of the two PDZ domains in NHERF1 to assemble
      protein complexes is allosterically modulated by the membrane-cytoskeleton linker
      protein ezrin, whose binding site is located as far as 110 Angstroms away from
      the PDZ domains. Here, using neutron spin echo (NSE) spectroscopy, selective
      deuterium labeling, and theoretical analyses, we reveal the activation of
      interdomain motion in NHERF1 on nanometer length-scales and on submicrosecond
      timescales upon forming a complex with ezrin. We show that a much-simplified
      coarse-grained model suffices to describe interdomain motion of a multidomain
      protein or protein complex. We expect that future NSE experiments will benefit by
      exploiting our approach of selective deuteration to resolve the specific domain
      motions of interest from a plethora of global translational and rotational
      motions. Our results demonstrate that the dynamic propagation of allosteric
      signals to distal sites involves changes in long-range coupled domain motions on
      submicrosecond timescales, and that these coupled motions can be distinguished
      and characterized by NSE.

PMID- 21081098
TI  - Nonlinear optical imaging and Raman microspectrometry of the cell nucleus
      throughout the cell cycle.
AB  - Fundamental understanding of cellular processes at molecular level is of
      considerable importance in cell biology as well as in biomedical disciplines for
      early diagnosis of infection and cancer diseases, and for developing new
      molecular medicine-based therapies. Modern biophotonics offers exclusive
      capabilities to obtain information on molecular composition, organization, and
      dynamics in a cell by utilizing a combination of optical spectroscopy and optical
      imaging. We introduce here a combination of Raman microspectrometry, together
      with coherent anti-Stokes Raman scattering (CARS) and two-photon excited
      fluorescence (TPEF) nonlinear optical microscopy, to study macromolecular
      organization of the nucleus throughout the cell cycle. Site-specific
      concentrations of proteins, DNA, RNA, and lipids were determined in nucleoli,
      nucleoplasmic transcription sites, nuclear speckles, constitutive heterochromatin
      domains, mitotic chromosomes, and extrachromosomal regions of mitotic cells by
      quantitative confocal Raman microspectrometry. A surprising finding, obtained in
      our study, is that the local concentration of proteins does not increase during
      DNA compaction. We also demonstrate that postmitotic DNA decondensation is a
      gradual process, continuing for several hours. The quantitative Raman
      spectroscopic analysis was corroborated with CARS/TPEF multimodal imaging to
      visualize the distribution of protein, DNA, RNA, and lipid macromolecules
      throughout the cell cycle.

PMID- 21081099
TI  - Interactions between amyloidophilic dyes and their relevance to studies of
      amyloid inhibitors.
AB  - Amyloid fibrils are filamentous aggregates of peptides and proteins implicated in
      a range of neurodegenerative disorders such as Alzheimer's and Parkinson's
      diseases. It has been known almost since their discovery that these beta-sheet
      rich proteinacious assemblies bind a range of specific dyes that, combined with
      other biophysical techniques, are convenient probes of the process of amyloid
      fibril formation. Two prominent examples of such dyes are Congo red (CR) and
      Thioflavin T (ThT). It has been reported that in addition to having a diagnostic
      role, CR is an inhibitor of the formation of amyloid structures, and these two
      properties have both been explained in terms of the same specific noncovalent
      interactions between the fibrils and the dye molecules. In this article, we show
      by means of quartz-crystal microbalance measurements that the binding of both ThT
      and CR to amyloid fibrils formed by the peptide whose aggregation is associated
      with Alzheimer's disease, Abeta(1-42), can be directly observed, and that the
      presence of CR interferes with the binding of ThT. Light scattering and
      fluorescence measurements confirm that an interaction exists between these dyes
      that can interfere with their ability to reflect accurately the quantity of
      amyloid material present in a given sample. Furthermore, we show that CR does not
      inhibit the process of amyloid fibril elongation, and therefore demonstrate the
      ability of the quartz-crystal microbalance method not only to detect and study
      the binding of small molecules to amyloid fibrils, but also to elucidate the mode
      of action of potential inhibitors.

PMID- 21081101
TI  - Kinetic mechanisms of Ca++/calmodulin dependent protein kinases.
AB  - Many of the cellular responses to Ca++ signaling are modulated by a family of
      multifunctional Ca++/calmodulin dependent protein kinases (CaMKs): CaMK I, CaMK
      II and CaMK IV. In order to further understand the role of CaMKs, we investigated
      the kinetic mechanism of CaMK II isozymes in comparison with those of CaMK I and
      CaMK IV by analyzing their steady state kinetics using phospholamban as a
      phosphoacceptor. The results indicated that (a) the CaMK family's reaction
      mechanisms were of the sequential type in which all substrates must bind to
      enzyme before any product is released; (b) CaMK I and CaMK IV exhibited random
      sequential mechanism where either phospholamban or ATP can bind to the free
      enzyme; (c) the data of product inhibition for CaMK IIs best fit with an Ordered
      Bi Bi mechanism in which phospholamban is the first substrate to bind and ADP is
      the last product to be released; and (d) the constant alpha (ratio of apparent
      dissociation constants for binding peptide in the presence and absence of the
      second ligand) of all isozymes for ATP and peptide was higher than 1 indicating
      that the binding of phospholamban to CaMK decreased the enzyme's affinity toward
      ATP.

PMID- 21081100
TI  - Single-molecule force spectroscopy of cartilage aggrecan self-adhesion.
AB  - We investigated self-adhesion between highly negatively charged aggrecan
      macromolecules extracted from bovine cartilage extracellular matrix by performing
      atomic force microscopy (AFM) imaging and single-molecule force spectroscopy
      (SMFS) in saline solutions. By controlling the density of aggrecan molecules on
      both the gold substrate and the gold-coated tip surface at submonolayer
      densities, we were able to detect and quantify the Ca(2+)-dependent homodimeric
      interaction between individual aggrecan molecules at the single-molecule level.
      We found a typical nonlinear sawtooth profile in the AFM force-versus-distance
      curves with a molecular persistence length of l(p) = 0.31 +/- 0.04 nm. This is
      attributed to the stepwise dissociation of individual glycosaminoglycan (GAG)
      side chains in aggrecans, which is very similar to the known force fingerprints
      of other cell adhesion proteoglycan systems. After studying the GAG-GAG
      dissociation in a dynamic, loading-rate-dependent manner (dynamic SMFS) and
      analyzing the data according to the stochastic Bell-Evans model for a thermally
      activated decay of a metastable state under an external force, we estimated for
      the single glycan interaction a mean lifetime of tau = 7.9 +/- 4.9 s and a
      reaction bond length of x(beta) = 0.31 +/- 0.08 nm. Whereas the x(beta)-value
      compares well with values from other cell adhesion carbohydrate recognition
      motifs in evolutionary distant marine sponge proteoglycans, the rather short GAG
      interaction lifetime reflects high intermolecular dynamics within aggrecan
      complexes, which may be relevant for the viscoelastic properties of cartilage
      tissue.

PMID- 21081102
TI  - Arsenic stress activates MAP kinase in rice roots and leaves.
AB  - The toxic metalloid arsenite has become a potential threat to rice growing
      regions leading to serious contamination in food chain. In the present study
      effect of different physiological concentration of arsenite that is toxic and
      triggers the molecular events were evaluated in rice seedlings. Along with severe
      effect on the growth of rice seedling, production of reactive oxygen species
      (ROS) and nitric oxide (NO) in arsenite treated rice roots was also observed.
      Activation of a 42kDa mitogen activated protein kinase (MAPK/MPK) by arsenite was
      observed in rice leaves and 42 and 44kDa in roots in dose dependent manner. The
      activated MAPK could be immunoprecipitated with anti-phospho-tyrosine antibody,
      4G10. The kinetic of MAPK activation by arsenite was found to be dose dependent.
      Transcript analysis of MAPK family and immunokinase assay in arsenite treated
      rice seedling revealed significant level of induction in OsMPK3 transcripts in
      leaves and OsMPK3, OsMPK4 transcripts in roots. Among MAPK kinase (MKKs) gene
      family, OsMKK4 transcripts were found to be induced in arsenite treated rice
      leaves and roots. In-silico homology modeling and docking analysis supported
      OsMPK3-OsMKK4 interaction. The data indicates that arsenite stress is transduced
      through MAPK signaling cascade in rice.

PMID- 21081103
TI  - Phosphomimicking mutations of human 14-3-3zeta affect its interaction with tau
      protein and small heat shock protein HspB6.
AB  - Effect of phosphomimicking mutations of 14-3-3zeta on its interaction with
      phosphorylated shortest isoform of human tau protein and phosphorylated human
      small heat shock protein HspB6 (Hsp20) was analyzed. Chemical crosslinking and
      native gel electrophoresis indicate that mutations S184E and T232E weakly affect
      interaction of 14-3-3 with phosphorylated tau protein, whereas mutations S58E and
      S58E/S184E/T232E significantly impair interaction of 14-3-3 and tau. Size
      exclusion chromatography, chemical crosslinking and immunoprecipitation revealed
      that phosphomimicking mutations S58E and S58E/S184E/T232E strongly decrease,
      mutation T232E weakly affects and mutation S184E improves interaction of 14-3-3
      with phosphorylated HspB6. Thus, mutation mimicking phosphorylation of Ser58
      dramatically decreases interaction of 14-3-3 with two target proteins and this
      effect might be due to destabilization of the dimeric structure of 14-3-3 and/or
      conformational changes of the target-binding site. The mutation mimicking
      phosphorylation of Thr232 weakly affects interaction of 14-3-3 with both
      proteins. The mutation mimicking phosphorylation of Ser184 does not markedly
      affect interaction with tau protein and improves the interaction of 14-3-3 with
      HspB6. Thus, effect of 14-3-3 phosphorylation depends on the nature of the target
      protein and therefore, phosphorylation of 14-3-3 might affect its target
      specificity.

PMID- 21081104
TI  - Microbial and host cells acquire enhanced oxidant-scavenging abilities by binding
      polyphenols.
AB  - The dilemma whether supplementations of dietary antioxidants might prevent the
      adverse consequences of oxidative stress, the inadequacy of the analytical
      methods employed to quantify oxidant scavenging ability (OSA) levels in whole
      blood and the distribution and fate of polyphenols and their metabolites in
      various body compartments following oral consumption are discussed. While none
      metabolized polyphenols might exert their antioxidant effects mainly in the oral
      cavity, metabolized polyphenols might be beneficial in the gastrointestinal tract
      to counteract the toxicity of oxidants and also of the sequelae of inflammatory
      processes. Although only micromolar amounts of polyphenols and their metabolites
      eventually reach the blood circulation, these may nevertheless still be highly
      effective as scavengers of reactive oxygen and nitrogen species because of their
      ability to synergize with plasma low molecular-weight antioxidants and with
      albumin. Polyphenols can avidly bind to surfaces of microorganisms and of blood
      cells to markedly enhance their OSA, therefore the routine quantifications of
      antioxidant levels conducted in clinical settings should always use catalase-rich
      whole blood but not as customary, plasma alone. In addition to their antioxidant
      and metal chelating properties, polyphenols may also act as signaling agents
      capable of affecting metabolic, inflammatory, autoimmune, carcinogenic and aging
      processes.

PMID- 21081105
TI  - Identification of a thioselenurane intermediate in the reaction between
      phenylaminoalkyl selenoxides and glutathione.
AB  - Selenium has a long history of association with human health and disease, and a
      low concentration of selenium in plasma has been identified in epidemiological
      studies as a risk factor for several disorders associated with oxidative stress.
      This association suggests that organoselenium compounds capable of propagating a
      selenium redox cycle might supplement natural cellular defenses against oxidants,
      such as peroxynitrite and hydrogen peroxide. While several such organoselenium
      compounds are under active investigation as potential therapeutic agents,
      chemical characterization of reaction intermediates involved in their redox
      cycling has been problematical. We now report evidence that the reaction between
      phenylaminoalkyl selenoxides and glutathione (GSH) proceeds through the
      intermediacy of a thioselenurane species. The results of stopped-flow kinetic
      experiments were consistent with a rapid and stoichiometric initial reaction of
      GSH with selenoxide to generate a kinetically-detectable intermediate, followed
      by a slower reaction of this intermediate with a second molecule of GSH to
      produce the final selenide and GSSG products. Flow injection ESI-MS and ESI-MS/MS
      experiments confirmed that the reaction intermediate is indeed a thioselenurane.
      Final structural characterization of the thioselenurane intermediate was obtained
      from analysis of the daughter ions produced in flow injection ESI-MS/MS
      experiments. These results help to elucidate the chemical nature of the redox
      cycling of phenylaminoalkyl selenides, and represent, to our knowledge, the first
      evidence for the intermediacy of a thioselenurane species in the reaction of
      thiols with selenoxides.

PMID- 21081107
TI  - Properties of tryptophan indole-lyase from a piezophilic bacterium,
      Photobacterium profundum SS9.
AB  - Tryptophan indole-lyase (Trpase), PBPRA2532, from Photobacterium profundum SS9, a
      piezophilic marine bacterium, has been cloned, expressed in Escherichia coli, and
      purified. The P. profundum Trpase (PpTrpase) exhibits similar substrate
      specificity as the enzyme from E. coli (EcTrpase). PpTrpase has an optimum
      temperature for activity at about 30 degrees C, compared with 53 degrees C for
      EcTrpase, and loses activity rapidly (t(1/2)~30min) when incubated at 50 degrees
      C, while EcTrpase is stable up to 65 degrees C. PpTrpase retains complete
      activity when incubated more than 3h at 0 degrees C, while EcTrpase has only
      about 20% remaining activity. Under hydrostatic pressure, PpTrpase remains fully
      active up to 100MPa (986atm), while EcTrpase exhibits only about 10% activity at
      100MPa. PpTrpase forms external aldimine and quinonoid intermediates in stopped
      flow experiments with l-Trp, S-Et-l-Cys, S-benzyl-l-Cys, oxindolyl-l-Ala, l-Ala
      and l-Met, similar to EcTrpase. However, with l-Trp a gem-diamine is observed
      that decays to a quinonoid complex. An aminoacrylate is observed with l-Trp in
      the presence of benzimidazole, as was seen previously with EcTrpase [28] but not
      with S-Et-l-Cys. The results show that PpTrpase is adapted for optimal activity
      in the low temperature, high pressure marine environment.

PMID- 21081108
TI  - Sphingosylphosphorylcholine and lysosulfatide have inverse regulatory functions
      in monocytic cell differentiation into macrophages.
AB  - Sphingolipids act as signaling mediators that regulate a diverse range of
      cellular events. Although numerous sphingolipid functions have been studied,
      little is known about the effect of sphingolipids on monocyte differentiation
      into macrophages. Here, we report that two lysosphingolipids,
      sphingosylphosphorylcholine (SPC) and lysosulfatide (LSF), inversely affect
      macrophagic differentiation of monocytic cell lines, U937 and THP-1. Molecular
      analyses revealed that SPC enhances, whereas LSF suppresses, phorbol ester
      induced classical (M1-polarized) differentiation to macrophages. The expression
      of CD11b, a macrophage marker, was induced in accordance with the activation
      status of the Raf/MEK/ERK signaling pathway in which SPC and LSF had opposite
      effects. Pharmacological inhibition of this pathway aborted the differentiation,
      indicating that this signaling pathway is required. Consistently, SPC promoted,
      while LSF inhibited, monocyte adhesion to fibronectin, through the
      phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The effects of SPC on
      Raf/MEK/ERK and PI3K/Akt signaling were dependent on G(i/o), whereas the SPC
      induced calcium influx was dependent on G(q). Thus SPC utilizes G-protein coupled
      receptor. In contrast, the effects of LSF were independent of G(i/o) and G(q).
      These results suggest that SPC enhances, whereas LSF suppresses, monocyte
      differentiation into macrophages through regulating the Raf/MEK/ERK and PI3K/Akt
      signaling pathways via distinct mechanisms.

PMID- 21081106
TI  - Enzymatic formation of apo-carotenoids from the xanthophyll carotenoids lutein,
      zeaxanthin and beta-cryptoxanthin by ferret carotene-9',10'-monooxygenase.
AB  - Xanthophyll carotenoids, such as lutein, zeaxanthin and beta-cryptoxanthin, may
      provide potential health benefits against chronic and degenerative diseases.
      Investigating pathways of xanthophyll metabolism are important to understanding
      their biological functions. Carotene-15,15'-monooxygenase (CMO1) has been shown
      to be involved in vitamin A formation, while recent studies suggest that carotene
      9',10'-monooxygenase (CMO2) may have a broader substrate specificity than
      previously recognized. In this in vitro study, we investigated baculovirus
      generated recombinant ferret CMO2 cleavage activity towards the carotenoid
      substrates zeaxanthin, lutein and beta-cryptoxanthin. Utilizing HPLC, LC-MS and
      GC-MS, we identified both volatile and non-volatile apo-carotenoid products
      including 3-OH-beta-ionone, 3-OH-alpha-ionone, beta-ionone, 3-OH-alpha-apo-10'
      carotenal, 3-OH-beta-apo-10'-carotenal, and beta-apo-10'-carotenal, indicating
      cleavage at both the 9,10 and 9',10' carbon-carbon double bond. Enzyme kinetic
      analysis indicated the xanthophylls zeaxanthin and lutein are preferentially
      cleaved over beta-cryptoxanthin, indicating a key role of CMO2 in non-provitamin
      A carotenoid metabolism. Furthermore, incubation of 3-OH-beta-apo-10'-carotenal
      with CMO2 lysate resulted in the formation of 3-OH-beta-ionone. In the presence
      of NAD(+), in vitro incubation of 3-OH-beta-apo-10'-carotenal with ferret hepatic
      homogenates formed 3-OH-beta-apo-10'-carotenoic acid. Since apo-carotenoids serve
      as important signaling molecules in a variety of biological processes, enzymatic
      cleavage of xanthophylls by mammalian CMO2 represents a new avenue of research
      regarding vertebrate carotenoid metabolism and biological function.

PMID- 21081109
TI  - Structural and functional analyses of PpENA1 provide insights into cation binding
      by type IID P-type ATPases in lower plants and fungi.
AB  - PpENA1 is a membrane-spanning transporter from the moss Physcomitrella patens,
      and is the first type IID P-type ATPase to be reported in the plant kingdom. In
      Physcomitrella, PpENA1 is essential for normal growth under moderate salt stress,
      while in yeast, type IID ATPases provide a vital efflux mechanism for cells under
      high salt conditions by selectively transporting Na+ or K+ across the plasma
      membrane. To investigate the structural basis for cation-binding within the type
      IID ATPase subfamily, we used homology modeling to identify a highly conserved
      cation-binding pocket between membrane helix (MH) 4 and MH 6 of the membrane
      spanning pore of PpENA1. Mutation of specific charged and polar residues on MHs 4
      6 resulted in a decrease or loss of protein activity as measured by
      complementation assays in yeast. The E298S mutation on MH 4 of PpENA1 had the
      most significant effect on activity despite the presence of a serine at this
      position in fungal type IID ATPases. Activity was partially restored in an
      inactivated PpENA1 mutant by the insertion of two additional serine residues on
      MH 4 and one on MH 6 based on the presence of these residues in fungal type IID
      ATPases. Our results suggest that the residues responsible for cation-binding in
      PpENA1 are distinct from those in fungal type IID ATPases, and that a fungal-type
      cation binding site can be successfully engineered into the moss protein.

PMID- 21081110
TI  - A glycosyltransferase-enriched reconstituted membrane system for the synthesis of
      branched O-linked glycans in vitro.
AB  - Mimicking the biochemical reactions that take place in cell organelles is
      becoming one of the most important challenges in biological chemistry. In
      particular, reproducing the Golgi glycosylation system in vitro would allow the
      synthesis of bioactive glycan polymers and glycoconjugates for many future
      applications including treatments of numerous pathologies. In the present study,
      we reconstituted a membrane system enriched in glycosyltransferases obtained by
      combining the properties of the wheat germ lectin with the dialysable detergent n
      octylglucoside. When applied to cells engineered to express the O-glycan
      branching enzyme core2 beta (1,6)-N-acetylglucosaminyltransferase (C2GnT-I), this
      combination led to the reconstitution of lipid vesicles exhibiting an enzyme
      activity 11 times higher than that found in microsomal membranes. The enzyme also
      showed a slightly higher affinity than its soluble counterpart toward the
      acceptor substrate. Moreover, the use of either the detergent re-solubilization,
      glycoprotein substrates or N-glycanase digestion suggests that most of the
      reconstituted glycosyltransferases have their catalytic domains in an
      extravesicular orientation. Using the disaccharide substrate Galbeta1-3GalNAc-O-p
      nitrophenyl as a primer, we performed sequential glycosylation reactions and
      compared the recovered oligosaccharides to those synthesized by cultured parental
      cells. After three successive glycosylation reactions using a single batch of the
      reconstituted vesicles and without changing the buffer, the acceptor was
      transformed into an O-glycan with chromatographic properties similar to glycans
      produced by C2GnT-I-expressing cells. Therefore, this new and efficient approach
      would greatly improve the synthesis of bioactive carbohydrates and
      glycoconjugates in vitro and could be easily adapted for the study of other
      reactions naturally occurring in the Golgi apparatus such as N-glycosylation or
      sulfation.

PMID- 21081111
TI  - Nature of sterols affects plasma membrane behavior and yeast survival during
      dehydration.
AB  - The plasma membrane (PM) is a main site of injury during osmotic perturbation.
      Sterols, major lipids of the PM structure in eukaryotes, are thought to play a
      role in ensuring the stability of the lipid bilayer during physicochemical
      perturbations. Here, we investigated the relationship between the nature of PM
      sterols and resistance of the yeast Saccharomyces cerevisiae to hyperosmotic
      treatment. We compared the responses to osmotic dehydration (viability, sterol
      quantification, ultrastructure, cell volume, and membrane permeability) in the
      wild-type (WT) strain and the ergosterol mutant erg6Delta strain. Our main
      results suggest that the nature of membrane sterols governs the mechanical
      behavior of the PM during hyperosmotic perturbation. The mutant strain, which
      accumulates ergosterol precursors, was more sensitive to osmotic fluctuations
      than the WT, which accumulates ergosterol. The hypersensitivity of erg6Delta was
      linked to modifications of the membrane properties, such as stretching resistance
      and deformation, which led to PM permeabilization during the volume variation
      during the dehydration-rehydration cycles. Anaerobic growth of erg6Delta strain
      with ergosterol supplementation restored resistance to osmotic treatment. These
      results suggest a relationship between hydric stress resistance and the nature of
      PM sterols. We discuss this relationship in the context of the evolution of the
      ergosterol biosynthetic pathway.

PMID- 21081113
TI  - Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic
      cancer cells.
AB  - The interaction between pancreatic cancer cells and pancreatic stellate cells
      (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing
      attention. There is accumulating evidence that PSCs promote the progression of
      pancreatic cancer by increasing cancer cell proliferation and invasion as well as
      by protecting them from radiation- and gemcitabine-induced apoptosis. Because
      epithelial-mesenchymal transition (EMT) plays a critical role in the progression
      of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer
      cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with
      human PSCs isolated from patients undergoing operation for pancreatic cancer. The
      expression of epithelial and mesenchymal markers was examined by real-time PCR
      and immunofluorescent staining. The migration of pancreatic cancer cells was
      examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured
      with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance.
      The expression of E-cadherin, cytokeratin 19, and membrane-associated beta
      catenin was decreased, whereas vimentin and Snail (Snai-1) expression was
      increased more in cancer cells co-cultured with PSCs than in mono-cultured cells.
      The migration of pancreatic cancer cells was increased by co-culture with PSCs.
      The PSC-induced decrease of E-cadherin expression was not altered by treatment
      with anti-TGF-beta-neutralizing antibody, excluding a central role of TGF-beta in
      this process. In conclusion, PSCs promoted EMT in pancreatic cancer cells
      suggesting a novel mechanism by which PSCs contribute to the aggressive behavior
      of pancreatic cancer cells.

PMID- 21081112
TI  - Evaluating reference genes to normalize gene expression in human epileptogenic
      brain tissues.
AB  - Several reference genes have been used to quantify gene expression in human
      epilepsy surgery tissue. However, their reliability has not been validated in
      detail, although this is crucial in interpreting epilepsy-related changes of gene
      expression. We evaluated 12 potential reference genes in neocortical tissues
      resected from patients with temporal lobe epilepsy (TLE) with either few or many
      seizures (n=6 each) and post mortem controls (n=6) using geNorm and NormFinder
      algorithms. For all candidate reference genes threshold cycle (C(T)) values were
      measured. geNorm analysis revealed that the expression of e.g. glyceraldehyde-3
      phosphate-dehydrogenase (GAPDH) and hypoxanthine phosphoribosyl-transferase
      (HPRT) is unstable, whereas synaptophysin (SYP) and neuron-specific enolase
      (NSE)/mitochondrial 39S ribosomal protein L28 (MRPL) are most stably expressed.
      The geometric mean of SYP, NSE and MRPL levels is recommended as normalization
      factor (NF). NormFinder analysis, in contrast, indicated HPRT as the most stable
      single gene and recommended the geometric mean of TATA-box binding protein (TBP)
      and NSE levels as NF. Different values of upregulation of glial fibrillary
      protein (GFAP) expression were found in TLE tissue compared to control tissue
      depending on the NF used: 4.5-fold (geNorm-NF), 4.7-fold (NormFinder-NF), 4.2
      fold (vs. GAPDH) and 7.8-fold (vs. HPRT). The expression of GABA(A) receptor
      subunit alpha5 (GARalpha5) was unaltered in the TLE groups compared to controls
      (geNorm-NF, NormFinder-NF, vs. GAPDH). However, normalization to HPRT suggests an
      apparent increase of GARalpha5 expression. In conclusion, the geNorm-NF
      (SYP/NSE/MRPL) and the NormFinder-NF (TBP/NSE) are equally suitable for
      normalization of gene expression in the human epileptogenic neocortex. In
      contrast, normalization to single and probably less stably expressed genes may
      not deliver accurate results.

PMID- 21081114
TI  - A technique for simultaneous measurement of force and overlap between single
      muscle filaments of myosin and actin.
AB  - In this study, we show a method for direct measurements of force and simultaneous
      visualization of isolated muscle filaments. Single actin filaments isolated from
      chicken skeletal muscle and single thick filaments isolated from Mussels were
      imaged using fluorescence and dark field microscopy, respectively. Force
      generated by the filaments was measured using micro-fabricated cantilevers. Force
      values were in the range observed previously with myosin filaments and molecules.
      The results suggest that the technique can be used to investigate many issues of
      interest and debate in the field of muscle biophysics.

PMID- 21081115
TI  - Topographical organization of human corpus callosum: an fMRI mapping study.
AB  - The concept of a topographical map of the corpus callosum (CC) has emerged from
      human lesion studies and from anatomical tracing investigations in other mammals.
      Over the last few years, a rising number of researchers have been reporting
      functional magnetic resonance imaging (fMRI) activation in white matter,
      particularly the CC. In this study, the scope for describing CC topography with
      fMRI was explored by evoking activation through simple sensory stimulation and
      motor tasks. We reviewed our published and unpublished fMRI data on the cortical
      representation of tactile, gustatory, and visual sensitivity and of motor
      activation, obtained in 36 volunteers. Activation foci were consistently detected
      in discrete CC regions: anterior (taste stimuli), central (motor tasks), central
      and posterior (tactile stimuli), and splenium (visual stimuli). These findings
      demonstrate that the functional topography of the CC can be explored with fMRI.

PMID- 21081117
TI  - Effects of minocycline on Na+ currents in rat dorsal root ganglion neurons.
AB  - Minocycline is an inhibitor of microglial activation and proliferation.
      Minocycline suppresses pain-related behaviors in many different pain states,
      which correlates closely with its inhibition of microglial activation and
      subsequent release of pro-inflammatory mediators in the spinal cord. Na(+)
      channels in dorsal root ganglion (DRG) neurons are implicated in the generation
      of inflammatory and neuropathic pain. To elucidate a possible peripheral
      mechanism of minocycline analgesia, effects of minocycline on tetrodotoxin
      sensitive and tetrodotoxin-resistant Na(+) currents in rat DRG neurons were
      investigated. Minocycline potently inhibited both types of Na(+) currents with
      IC(50) values of 350 nM and 410 nM, respectively. The inhibition was accompanied
      by a depolarizing shift of the activation voltage. However, minocycline slowed
      the inactivation and speeded up the recovery from inactivation. These results
      suggest minocycline may exert analgesia peripherally thorough Na(+) channel
      inhibition in the primary afferent neurons as well as centrally through
      microglial inhibition in the spinal cord.

PMID- 21081116
TI  - Brain metabolite concentrations across cortical regions in healthy adults.
AB  - Magnetic resonance spectroscopy (MRS) can provide in vivo information about
      metabolite levels across multiple brain regions. This study used MRS to examine
      concentrations of N-acetylaspartate (NAA), a marker of neuronal integrity and
      function, and choline (Cho), which is related to the amount of cell membrane per
      unit volume, in anterior cingulate cortex (ACC) and parieto-occipital cortex
      (POC) in healthy individuals. Data were drawn from two experiments which examined
      glutamatergic and GABAergic signaling in schizophrenia and bipolar disorder.
      After controlling for gray matter percentages, NAA/creatine (Cr) was 18% higher
      in POC than in ACC (p<0.001); Cho/Cr was 46% lower in POC than in ACC (p<0.001).
      There was an effect of study (p<0.001 for both metabolites), but no region by
      study interaction (NAA p=0.101, Cho p=0.850). Since NAA is localized to the
      intracellular space, these data suggest that ACC neuronal compartment is reduced
      as compared with POC, or that there is a lower concentration of NAA per cell in
      the ACC than POC, or both. Since elevated Cho suggests more cell membrane per
      unit volume, reduced NAA in ACC appears to be coupled with increases in overall
      cell membrane compartment. These findings are consistent with a number of
      previous studies using proton MRS which found increasing NAA and decreasing Cho
      moving caudally, and with postmortem anatomical studies which found neurons in
      more widely spaced bundles in ACC when compared to parietal and occipital
      cortices. MRS may be a useful tool for studying physical properties of the living
      human brain.

PMID- 21081118
TI  - EGF induces CREB and ERK activation at the wall of the mouse lateral ventricles.
AB  - The subependymal zone at the lateral ventricular wall represents a major
      neurogenic niche of the adult mammalian brain and continuously provides new
      neurons for the olfactory bulb. A mosaic of stem and progenitor cells in this
      niche has the potential to respond to multiple signals including growth factors
      such as EGF. Recent studies using long-term ventricular infusion of EGF
      demonstrate intense cell proliferation around the ventricular wall, implicating
      the presence of EGF-reactive cells also outside the classical neurogenic lateral
      niche. Here we show that intraventricular injection of EGF induces within minutes
      CREB and ERK phosphorylation in astrocyte-like progenitor cells (type B cells)
      and EGF receptor-expressing transit-amplifying progenitor cells-both in the
      striatal and septal ventricular walls. EGF infusion for 6 days induced continued
      CREB and ERK activation in nestin+ cells paralleled by intense periventricular
      cell proliferation. In addition, the ependyma became EGF receptor-immunoreactive,
      revealed intense CREB phosphorylation and underwent partial de-differentiation.
      Our results demonstrate that intraventricular application of EGF induces CREB and
      ERK phosphorylation along the entire ventricular walls and thus permits a direct
      identification of EGF-responsive cell types. They further support the notion that
      not only the striatal ventricular wall where the SEZ is located but also the
      septal ventricular wall carries latent potential for the formation of neurons and
      glial cells.

PMID- 21081120
TI  - More innovation and evidence of their usefulness are needed in the pre-analytical
      area.

PMID- 21081119
TI  - Multiple neurofilament subunits are present in lamprey CNS.
AB  - In mammals, there are three neurofilament (NF) subunits (NF-L, NF-M, and NF-H),
      but it was thought that only a single NF, NF180, exists in lamprey. However,
      NF180 lacked the ability to self-assemble, suggesting that like mammalian NFs,
      lamprey NFs are heteropolymers, and that additional NF subunits may exist. The
      present study provides evidence for the existence of a lamprey NF-L homolog (L
      NFL). Genes encoding two new NF-M isoforms (NF132 and NF95) also have been
      isolated and characterized. With NF180, this makes three NF-M-like isoforms. In
      situ hybridization showed that all three newly cloned NFs are expressed in spinal
      cord neurons and in spinal-projecting neurons of the brainstem. Like NF180, there
      were no KSP multiphosphorylation repeat motifs in the tail regions of NF132 or
      NF95. NF95 was highly identical to homologous parts of NF180, sharing 2 common
      pieces of DNA with it. Northern blots suggested that NF95 may be expressed at
      very low levels in older larvae. The presence of L-NFL in lamprey CNS may support
      the hypothesis that as in mammals, NFs in lamprey are obligate heteropolymers, in
      which NF-L is a required subunit.

PMID- 21081122
TI  - The unique and cooperative roles of the Grainy head-like transcription factors in
      epidermal development reflect unexpected target gene specificity.
AB  - The Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays
      essential roles in epidermal morphogenesis during embryonic development, with
      deficient mice exhibiting failed skin barrier formation, defective wound repair,
      and loss of eyelid fusion. Despite sharing significant sequence homology,
      overlapping expression patterns, and an identical core consensus DNA binding
      site, the other members of the Grhl family (Grhl1 and -2) fail to compensate for
      the loss of Grhl3 in these processes. Here, we have employed diverse genetic
      models, coupled with biochemical studies, to define the inter-relationships of
      the Grhl factors in epidermal development. We show that Grhl1 and Grhl3 have
      evolved complete functional independence, as evidenced by a lack of genetic
      interactions in embryos carrying combinations of targeted alleles of these genes.
      In contrast, compound heterozygous Grhl2/Grhl3 embryos displayed failed wound
      repair, and loss of a single Grhl2 allele in Grhl3-null embryos results in fully
      penetrant eyes open at birth. Expression of Grhl2 from the Grhl3 locus in
      homozygous knock-in mice corrects the wound repair defect, but these embryos
      still display a complete failure of skin barrier formation. This functional
      dissociation is due to unexpected differences in target gene specificity, as both
      GRHL2 and GRHL3 bind to and regulate expression of the wound repair gene Rho GEF
      19, but regulation of the barrier forming gene, Transglutaminase 1 (TGase1), is
      unique to GRHL3. Our findings define the mechanisms underpinning the unique and
      cooperative roles of the Grhl genes in epidermal development.

PMID- 21081121
TI  - Endothelial cell talin1 is essential for embryonic angiogenesis.
AB  - Using Tln1(fl/fl);CreER mice, we show that tamoxifen-induced inactivation of the
      talin1 gene throughout the embryo produces an angiogenesis phenotype that is
      restricted to newly forming blood vessels. The phenotype has a rapid onset in
      early embryos, resulting in vessel defects by 48 h and death of the embryo within
      72 h. Very similar vascular defects were obtained using a Tie2-Cre endothelial
      cell-specific Tln1 knockout, a phenotype that was rescued by expression of a Tln1
      mini-gene in endothelial cells. We show that endothelial cells, unlike most other
      cell types, do not express talin2, which can compensate for loss of talin1, and
      demonstrate for the first time that endothelial cells in vivo lacking talin1 are
      unable to undergo the cell spreading and flattening required to form vessels.

PMID- 21081123
TI  - Influence and timing of arrival of murine neural crest on pancreatic beta cell
      development and maturation.
AB  - Interactions between cells from the ectoderm and mesoderm influence development
      of the endodermally-derived pancreas. While much is known about how mesoderm
      regulates pancreatic development, relatively little is understood about how and
      when the ectodermally-derived neural crest regulates pancreatic development and
      specifically, beta cell maturation. A previous study demonstrated that signals
      from the neural crest regulate beta cell proliferation and ultimately, beta cell
      mass. Here, we expand on that work to describe timing of neural crest arrival at
      the developing pancreatic bud and extend our knowledge of the non-cell autonomous
      role for neural crest derivatives in the process of beta cell maturation. We
      demonstrated that murine neural crest entered the pancreatic mesenchyme between
      the 26 and 27 somite stages (approximately 10.0 dpc) and became intermingled with
      pancreatic progenitors as the epithelium branched into the surrounding
      mesenchyme. Using a neural crest-specific deletion of the Forkhead transcription
      factor Foxd3, we ablated neural crest cells that migrate to the pancreatic
      primordium. Consistent with previous data, in the absence of Foxd3, and therefore
      the absence of neural crest cells, proliferation of insulin-expressing cells and
      insulin-positive area are increased. Analysis of endocrine cell gene expression
      in the absence of neural crest demonstrated that, although the number of insulin
      expressing cells was increased, beta cell maturation was significantly impaired.
      Decreased MafA and Pdx1 expression illustrated the defect in beta cell
      maturation; we discovered that without neural crest, there was a reduction in the
      percentage of insulin-positive cells that co-expressed Glut2 and Pdx1 compared to
      controls. In addition, transmission electron microscopy analyses revealed
      decreased numbers of characteristic insulin granules and the presence of abnormal
      granules in insulin-expressing cells from mutant embryos. Together, these data
      demonstrate that the neural crest is a critical regulator of beta cell
      development on two levels: by negatively regulating beta cell proliferation and
      by promoting beta cell maturation.

PMID- 21081124
TI  - Crucial role of the influenza virus NS2 (NEP) C-terminal domain in M1 binding and
      nuclear export of vRNP.
AB  - The influenza virus genome replicates in the host cell nucleus, and the progeny
      viral ribonucleoproteins (vRNPs) are exported to the cytoplasm prior to
      maturation. The influenza virus NS2 protein has a nuclear export signal (NES) and
      binds to M1. It is therefore postulated that vRNP is exported from the nucleus by
      binding to NS2 through M1. However, the significance of the association between
      NS2 and M1 for the nuclear export of vRNP is still poorly understood. We herein
      demonstrate that the C-terminal domain of NS2 (residues 81-100) is essential for
      M1 binding and the nuclear export of progeny vRNPs.

PMID- 21081126
TI  - Anti-apoptotic protein TCTP controls the stability of the tumor suppressor p53.
AB  - In this study, we identified p53 as a novel TCTP-interacting protein using TCTP
      as bait. Also, we determined the critical binding sites between TCTP and p53. To
      elucidate the functional consequence of the interaction, we developed the
      overexpression and inhibition system of TCTP and p53 expression. Overexpression
      of TCTP in lung carcinoma cells reversed p53 mediated apoptosis and inhibition of
      TCTP expression by small interfering RNA increased apoptosis of lung carcinoma
      cells. Moreover, it was observed that TCTP overexpression promotes degradation of
      p53. These results clearly indicate that the interaction between TCTP and p53
      prevents apoptosis by destabilizing p53. Thus, TCTP acts as a negative regulator
      of apoptosis in lung cancer.

PMID- 21081125
TI  - Chromatin structure as a mediator of aging.
AB  - The aging process is characterized by gradual changes to an organism's
      macromolecules, which negatively impacts biological processes. The complex
      macromolecular structure of chromatin regulates all nuclear processes requiring
      access to the DNA sequence. As such, maintenance of chromatin structure is an
      integral component to deter premature aging. In this review, we describe current
      research that links aging to chromatin structure. Histone modifications influence
      chromatin compaction and gene expression and undergo many changes during aging.
      Histone protein levels also decline during aging, dramatically affecting
      chromatin structure. Excitingly, lifespan can be extended by manipulations that
      reverse the age-dependent changes to chromatin structure, indicating the pivotal
      role chromatin structure plays during aging.

PMID- 21081127
TI  - Role of protein kinase C and mitochondrial permeability transition pore in the
      neuroprotective effect of ceramide in ischemia-induced cell death.
AB  - In this study, we investigated the role of protein kinase C (PKC) and
      mitochondrial permeability transition pore (mPTP) on the effect of ceramide in an
      in vitro model of ischemia in SH-SY5Y neuroblastoma cells. In ischemic cell
      viability studies, a dual effect of ceramide was observed, depending on ceramide
      concentration. PKC isoforms are involved in the protective effect of low
      concentrations of ceramide. During ischemia, ceramide treatment leads to an
      increase in the formation of reactive oxygen species (ROS), which induces a
      controlled opening of mPTP. This fact prevents mitochondrial Ca(2+) overload,
      which is clearly protective.

PMID- 21081129
TI  - Effects of metolachlor on transcription of thyroid system-related genes in
      juvenile and adult Japanese medaka (Oryzias latipes).
AB  - Metolachlor (MT) is one of the most important pesticides applied to corn and
      other crops for controlling broadleaf and grass weeds. However, the effects of MT
      on the thyroid system in fish remain to be elucidated. In the present experiment,
      transcription of genes related to the thyroid system, including thyrotropin
      releasing hormone (Trh), deiodinase 2 (Dio2), thyroid hormone receptor alpha
      (Thralpha), and thyroid hormone receptor beta (Thrbeta), were induced by MT in a
      sex-, developmental stage-, and tissue- specific manner when medaka were exposed
      to various concentrations of MT for 14 days. The transcriptional levels of the
      genes were only significantly altered in both juvenile and adult female medaka in
      response to MT exposure. And the lowest concentrations able to significantly
      induce transcription of the selected genes were 10 and 100 MUg/L in juvenile and
      adult female medaka, respectively. In adult female medaka, a significant up
      regulation of these genes was detected only in the brain, with little or no
      effect in the liver. Furthermore, MT-induced (100 MUg/L) transcription of thyroid
      system-related genes was enhanced significantly in male juvenile medaka in the
      presence of estrogen (E2) (50 and 100 ng/L). Moreover, the mRNA levels of
      Thralpha and Thrbeta in males increase with the combined treatments of 100 MUg/L
      MT and 100 ng/L E2. Dio2 increased when exposed to 100 MUg/L MT and 50 or 100
      ng/L E2. The information obtained in the present study suggests that MT has the
      potential to influence several steps of the hypothalamus-pituitary-thyroid (HPT)
      axis homeostasis and to disrupt the thyroid system in medaka.

PMID- 21081128
TI  - Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development.
AB  - BACKGROUND & AIMS: Caudal-related homeobox protein 2 (Cdx2) is an intestine
      specific transcription factor that is important for intestinal development and
      intestine-specific gene expression. Cdx2 regulates intestinal cell-cell adhesion,
      proliferation, and the transcriptional activities of Wnt and beta-catenin in cell
      culture systems. We generated transgenic mice that overexpress Cdx2 in the small
      intestinal and colonic epithelium to investigate the role of Cdx2 in
      differentiation and function of the intestinal epithelium. METHODS: We
      established 4 different lines of villin-Cdx2 transgenic mice. Intestines were
      collected from infant, 3-month old, and wild-type mice. Genes of interest and
      cell lineage markers were examined by polymerase chain reaction and
      immunohistochemistry. RESULTS: Villin-Cdx2 transgenic mice had complex phenotypes
      that were associated with transgene expression levels. The 2 lines that had the
      greatest levels of transgene expression had significant, preweaning failure to
      grow and death; these were the result of early epithelial maturation and
      alterations in nutrient digestion and absorption. Fat malabsorption was a
      prominent feature. Other effects associated with the transgene expression
      included loss of Paneth cell markers, increases in goblet cells, and migration of
      proliferating, EphB2-expressing cells to the crypt base. Loss of Paneth cell
      markers was associated with reduced nuclear localization of beta-catenin but not
      homeotic posteriorization of the epithelium by Cdx2. CONCLUSIONS: Overexpression
      of Cdx2 in the small intestine is associated with reduced post-natal growth,
      early epithelial maturation, alterations in crypt base organization, and changes
      in Paneth and goblet cell lineages. Cdx2 is a critical regulator not only of
      intestine-specific genes, but also processes that determine epithelial maturity
      and function.

PMID- 21081130
TI  - Male sexual behavior does not require elevated testosterone in a lizard (Coleonyx
      elegans, Eublepharidae).
AB  - Male sexual behavior depends on gonadal androgens in species of all major
      vertebrate lineages, including reptiles. However, male sexual behavior includes
      distinct appetitive and consummatory phases, typically denoted as courtship and
      mounting, with potentially different hormonal control. Different proximate
      controls of courtship versus mounting could enable disconnected evolutionary
      losses and gains of various aspects of male sexual behavior. Male courtship
      display, which is activated by testosterone (T) in many species, is an ancestral
      trait in the lizard family Eublepharidae. However, Coleonyx elegans (Yucatan
      Banded Gecko) lost the courtship display, while retaining a highly simplified
      male sexual behavior that involves only mounting for copulation. We performed
      surgical manipulations (castration with and without T replacement in adult males;
      implantation of adult females with exogenous T) to investigate hormonal
      mechanisms involved in this evolutionary novelty. Our results indicate that the
      expression of simplified sexual behavior in C. elegans does not require elevated
      circulating levels of T, a finding that is previously unreported in lizards. In
      females, however, exogenous T induced male-like mounting. Thus, the mounting
      phase of sexual behavior is not activated by T in the traditional sense of this
      term but probably requires post-natal, maturational organization (if not periodic
      reorganization) by androgens. We conclude that the simplification of male sexual
      behavior and its independence from elevated levels of circulating androgens in C.
      elegans evolved via 1) evolutionary loss of the androgen-activated courtship
      display and 2) retention of the mounting phase, which has a longer "functional
      memory" for the effects of androgenic steroids.

PMID- 21081131
TI  - Impact of sex on hyperalgesia induced by sleep loss.
AB  - This study evaluated the impact of sex on the short term consequences of
      different periods of sleep deprivation and the effect of the respective sleep
      recovery periods on nociceptive responses. Male and female C57BL/6J mice were
      assigned to the following groups: paradoxical sleep deprived (PSD) for 72 h,
      sleep restricted (SR) for 15 days, exposed to respective recovery periods for 24
      h, or untreated home-cage controls (CTRL). Mice were submitted to a noxious
      thermal stimulus to evaluate their nociceptive response after PSD, SR, or
      recovery periods. Blood was collected for hormonal analysis. The nociceptive
      response was significantly lower in PSD and SR mice compared to CTRL animals,
      regardless of the sex. However, SR females had a lower paw withdrawal threshold
      than males. Sleep recovery was able to restore normal nociceptive sensitivity
      after PSD in both sexes. The hyperalgesia induced by SR was not reversed by sleep
      rebound. In females, low concentrations of estradiol were found after SR, and
      these concentrations continued to decrease after 24 hours of sleep recovery. The
      PSD male mice exhibited higher concentrations of corticosterone than the CTRL and
      SR male mice. Corticosterone levels were not affected by SR. Our study revealed
      that PSD and SR induce hyperalgesia in mice. The SR groups showed marked changes
      in the nociceptive response, and the females were more sensitive to these
      alterations. This finding indicates that, although different periods of sleep
      deprivation change the nociceptive sensitivity in male and female mice, sex could
      influence hyperalgesia induced by chronic sleep loss.

PMID- 21081132
TI  - Social modulation of testosterone levels in male black howlers (Alouatta pigra).
AB  - The influence of social factors on the modulation of male testosterone levels has
      been demonstrated among several vertebrate species. In addition to sexual
      activity, parental care and reproductive competition affect testosterone
      secretion. We examined variations in testosterone levels among male black howlers
      (Alouatta pigra) in various social contexts. Fecal samples were collected from
      nine males living in five different groups in the Mexican state of Campeche. The
      potential for intragroup and extragroup competition varied among the groups. The
      number of resident males living in the groups was the only variable that
      significantly explained variations in testosterone levels. Males living in
      unimale groups had higher testosterone levels; the highest testosterone levels
      were recorded for males that had experienced a shift from multimale to unimale
      group compositions. In this species, the probability of being challenged by
      extragroup males and evicted from the group during immigration events increases
      when males live in unimale groups. Therefore, our results suggest that male black
      howlers respond to competition for group membership by increasing their
      testosterone levels. In this context, testosterone secretion represents an
      anticipatory response to reproductive conflicts. Therefore, although males living
      in unimale groups have exclusive access to females, they face higher
      physiological costs associated with sustaining high testosterone levels for
      extended time periods.

PMID- 21081133
TI  - Fish trophic level and the similarity of non-specific larval parasite
      assemblages.
AB  - Whereas the effect of parasites on food webs is increasingly recognised and has
      been extensively measured and modelled, the effect of food webs on the structure
      of parasite assemblages has not been quantified in a similar way. Here, we apply
      the concept of decay in community similarity with increasing distance, previously
      used for parasites in geographical, phylogenetic and ontogenetic contexts, to
      differences in the trophic level (TL) based on diet composition of fishes. It is
      proposed as an accurate quantitative method to measure rates of assemblage change
      as a function of host feeding habits and is applied, to our knowledge for the
      first time, across host species in marine waters. We focused on a suite of 15
      species of trophically-transmitted and non-specific larval helminths across 16
      fish species (1783 specimens, six orders, 14 families) with different sizes and
      TLs, gathered from the same ecosystem. Not all host species harboured the same
      number and types of parasites, reflecting the differences in their ecological
      characteristics. Using differences in TL and body length as measurements of size
      and trophic distances, we found that similarity at both infracommunity and
      component community levels showed a very clear decay pattern, based on parasite
      abundance and relative abundance, with increasing distance in TL, but was not
      related to changes in fish size, with TL thus emerging as the main explanatory
      factor for similarity of parasite assemblages. Furthermore, the relationships
      between host TL and assemblage similarity allowed identification of fishes for
      which the TL was under- or over-estimated and prediction of the TL of host
      species based on parasite data alone.

PMID- 21081134
TI  - Inhibition of intimal hyperplasia after stenting by over-expression of p15: a
      member of the INK4 family of cyclin-dependent kinase inhibitors.
AB  - We evaluated the role of p15(Ink4), a member of the INK4 family of CDK inhibitors
      on vascular smooth muscle cells (VSMCs) proliferation, cell cycle progression and
      intimal hyperplasia after stenting. Aortic VSMCs transduced with either
      adenovirus encoding for p15(Ink4) or beta-galactosidase were assessed for DNA
      synthesis, cell cycle progression, and pRb phosphorylation. Rabbit carotid
      arteries were stented and treated with peri-adventitial delivery of saline or
      adenovirus encoding for p15(Ink4) or beta-galactosidase. p15(Ink4) transgene and
      protein expression were evaluated at 24 h and 72 h, respectively. In-stent cell
      proliferation was evaluated by BrdU at day 7. Histomorphometric analysis of in
      stent intimal hyperplasia was performed at 10 weeks. Human p15(Ink4) DNA was
      detected in transduced VSMCs at 24h. p15(Ink4) over-expression reduced VSMCs DNA
      synthesis by 60%. Cell cycle progression was inhibited, with a 30% increase in G1
      population accompanied by inhibition of pRb phosphorylation. Human p15(Ink4)
      transgene was identified in transduced stented arteries but not in control
      arteries. p15(Ink4) immunostaining was increased and cell proliferation
      significantly reduced by 50% in p15(Ink4) transduced arteries. Intimal cross
      sectional area (CSA) of p15(Ink4)-treated group was significantly lower than the
      beta-gal treated and non-transduced groups (p=0.008). There were no differences
      in the intimal or medial inflammatory response between groups. p15(Ink4) over
      expression blocks cell cycle progression leading to inhibition of VSMCs
      proliferation. Peri-adventitial delivery of p15(Ink4) significantly inhibits in
      stent intimal hyperplasia.

PMID- 21081135
TI  - Natural and synthetic corticosteroids inhibit uptake 2-mediated transport in CNS
      neurons.
AB  - In addition to exerting actions via mineralocorticoid and glucocorticoid
      receptors, corticosteroids also act by inhibiting uptake(2), a high-capacity
      monoamine transport system originally described in peripheral tissues. Recent
      studies have demonstrated that uptake(2) transporters are expressed in the brain
      and play roles in monoamine clearance, suggesting that they mediate some
      corticosteroid effects on physiological and behavioral processes. However, the
      sensitivity of brain uptake(2) to many natural and synthetic corticosteroids has
      not been characterized. Cultured rat cerebellar granule neurons (CGNs) were
      previously shown to exhibit corticosterone-sensitive accumulation of the
      uptake(2) substrate 1-methyl-4-phenylpyridinium (MPP(+)). We examined the
      expression of uptake(1) and uptake(2) transporters in CGNs, and tested the
      effects of a variety of natural and synthetic corticosteroids on accumulation of
      [(3)H]-MPP(+) by these cells. Cultured rat CGNs expressed mRNA for three
      uptake(2)-like transporters: organic cation transporters 1 and 3, and the plasma
      membrane monoamine transporter. They did not express mRNA for the dopamine or
      norepinephrine transporters, and expressed very little mRNA for the serotonin
      reuptake transporter. Accumulation of [(3)H]-MPP(+) by CGNs was dose-dependently
      inhibited by corticosterone and decynium-22, known inhibitors of uptake(2).
      Accumulation of MPP(+) was also dose-dependently inhibited, with varying
      efficacies, by aldosterone, 11-deoxycorticosterone, cortisol, and cortisone, and
      by the synthetic glucocorticoids betamethasone, dexamethasone and prednisolone,
      and the glucocorticoid receptor antagonist RU38486. These studies demonstrate
      that uptake(2) in the CNS is inhibited by a variety of natural and synthetic
      corticosteroids, and suggest that inhibition of uptake(2)-mediated monoamine
      clearance may underlie some behavioral and physiological effects of these
      hormones.

PMID- 21081136
TI  - Backward conditioning of tumor necrosis factor-alpha in a single trial: changing
      intervals between exposures to lipopolysaccharide and saccharin taste.
AB  - The current study examined the effect of backward conditioning with three
      different time intervals between exposures to lipopolysaccharide (LPS) as the
      unconditioned stimulus (US) and saccharin taste in water as the potential
      conditioned stimulus (CS). Forty-eight naive female BALB/c mice at three months
      of age served as subjects, divided into six groups. Four groups were assigned to
      Experiment 1 for the tumor necrosis factor alpha (TNF-alpha) measure, and the
      remaining two groups were used in Experiment 2 to measure taste aversion
      behavior. Both experiments employed a single trial. The timing of introduction to
      the saccharin taste varied between 3 min, 7 h, and 24 h following an LPS
      injection in Experiment 1. Experiment 2 employed the three-minute interval only.
      These intervals correspond to distinct immunological, physiological, and
      behavioral events induced by LPS. On the day after re-exposure to the saccharin
      taste, the TNF-alpha groups were challenged with LPS to test the LPS tolerance
      response. While backward conditioning of taste aversion behavior was not
      observed, some evidence of conditioned TNF-alpha response and subsequent
      development of LPS tolerance was observed with backward conditioning in a single
      trial. This exploratory study demonstrated that the effect of backward
      conditioning on conditioned TNF-alpha response and LPS tolerance response in a
      single trial depended on the timing of when a CS is presented after LPS exposure.

PMID- 21081138
TI  - Advances in Enzyme Regulation. Foreword.

PMID- 21081137
TI  - Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal
      mechanistic insights and new candidate biomarkers.
AB  - The European InnoMed-PredTox project was a collaborative effort between 15
      pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities
      with the goal of delivering deeper insights into the molecular mechanisms of
      kidney and liver toxicity and to identify mechanism-linked diagnostic or
      prognostic safety biomarker candidates by combining conventional toxicological
      parameters with "omics" data. Mechanistic toxicity studies with 16 different
      compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han)
      rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin
      (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In
      addition to histopathology and clinical chemistry, transcriptomics microarray and
      proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were
      combined for a cross-study and cross-omics meta-analysis of the target organ. The
      mechanistic interpretation of kidney PTD-associated deregulated transcripts
      revealed, in addition to previously described kidney damage transcript biomarkers
      such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways
      congruent with histopathology observations on a single animal basis, including a
      specific effect on the complement system. The identification of new, more
      specific biomarker candidates for PTD was most successful when transcriptomics
      data were used. Combining transcriptomics data with proteomics data added extra
      value.

PMID- 21081139
TI  - Up-regulation of lymphocytic growth hormone secretion during the luteal phase of
      cycle and early pregnancy.
AB  - Growth hormone (GH) has been shown to be produced and secreted by peripheral
      immune cells. Therefore, we studied the release of GH by lymphocytes, during
      various stages of pregnancy and estrous cycle in the cow. The effect of leptin on
      the lymphocytic GH release was also investigated. Estradiol-17beta and
      progesterone concentrations in plasma were measured in all animals to confirm
      their reproductive status. Growth hormone levels measured in cell cultures during
      early pregnancy (days 60-80) and during the luteal phase were greater (p <= 0.01)
      than levels during follicular phase or mid (days 100-160) and late (days 240-245)
      pregnancy. Leptin treatment stimulated (p <= 0.05) lymphocytic GH release during
      mid-pregnancy when the basal GH levels were low. Changes in lymphocytic GH
      release and elevation of lymphocytic GH secretion by leptin during pregnancy and
      the absence of such effects in estrous cycle may indicate that leptin modulation
      of lymphocytic GH plays a role in the regulation of immune response during
      pregnancy.

PMID- 21081140
TI  - Optimization of processing conditions for the quantification of enterococci
      biofilms using microtitre-plates.
AB  - We performed a comparison of four selected protocols from the literature using
      microtitre-plate and colorimetric biomass assay for evaluation of enterococci
      biofilm formation ability and optimized a protocol after the identification and
      stringent performance of biofilm formation steps. The optimized protocol uses a
      dynamic model that provided a greater discrimination of enterococci biofilm
      formation ability, and could better simulate in vivo real conditions. Moreover
      different biofilm quantification approaches, such as the colorimetric biomass
      (crystal violet), the resazurin and CFU's assays could be used with the optimized
      protocol, with adequate reproducibility. This study also recognizes that
      parameters such as the biofilm formation index (BFi), the cut-off values and the
      Z' factor provide greater accuracy, possibility of inter and intra laboratory
      comparison and quality evaluation of the biofilm screening assays, respectively.

PMID- 21081141
TI  - A human single-chain variable fragment targeting to Vibrio vulnificus RtxA toxin.
AB  - Vibrio vulnificus secretes a multifunctional cytotoxin RtxA (VvRtxA), which plays
      a major role in the bacterial pathogenesis. The lack of an efficient VvRtxA
      detection tool has hampered the progress of V. vulnificus pathogenesis research.
      This study aims to isolate VvRtxA specific single-chain variable fragments (scFv)
      to serve as a detection agent. The VvRtxA C-terminal Gly-Asp (GD) repeat
      containing region, which has been implicated for calcium binding and target cell
      recognition, was chosen as an antigen to screen a scFv phage display library. A
      scFv clone that reacted positively to VvRtxA was successfully obtained. Using the
      isolated scFv, a cell-based enzyme-linked immunosorbent assay was established for
      detecting cell-associated VvRtxA toxin in V. vulnificus infected HEp-2 cells. The
      result is consistent with previous observations that secretion of VvRtxA toxin is
      time-dependent on bacteria contacting with host cells. Utilization of scFv for
      VvRtxA toxin detection provides an applicable strategy devoid of conventional
      immunization.

PMID- 21081142
TI  - How much cytoplasm can a bacterial genome control?
AB  - In this perspective we discuss that bacterial genomes have optimized during
      evolution to control a range of cytoplasm, from immediately after cell division
      to a maximum amount/volume present just prior to DNA replication and subsequent
      cell division. The genetic expansion of bacteria via evolution may be limited to
      a genome size:cytoplasm amount/volume ratios and energetics that have been
      selected for during 3.6-4 billion years of evolution on the Earth. The optimal
      genome size is one that is relatively constant, but also has some plasticity for
      evolutionary change (via gene transfer) and mutational events, and can control a
      range of cytoplasm during the cell cycle.

PMID- 21081144
TI  - Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease
      occurrence in Tunisian patients receiving a human leukocyte antigen-identical
      sibling hematopoietic stem cell transplant.
AB  - The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may
      be critical and can affect the functional activity of cells that initiate the
      graft-versus-host disease (GVHD) effects. The aim of this study is to examine the
      effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G
      polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total
      of 112 patients and their 112 respective sibling donors of HSCs were enrolled in
      this study. All patients had either grades 0-I or grades II-IV acute GVHD, or
      chronic GVHD. The SNPs genotyping assay was performed using sets of sequence
      specific primers (SSP-PCR). The single marker association analysis showed that
      the 49G allele, in a genetic recessive model, may be a potential risk factor only
      for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval
      = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide
      combination is significantly associated with the incidence of chronic GVHD (p =
      0.043, chi2 = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk
      factor for developing chronic GVHD after allo-stem cell transplantation. We
      suppose that donor T cells expressing this haplotype in a homozygous state have
      higher proliferation than those expressing other haplotypes, especially after
      recognition of the recipient's minor histocompatibility antigens.

PMID- 21081143
TI  - Cortical gamma responses: searching high and low.
AB  - In this paper, a brief, preliminary attempt is made to frame a scientific debate
      about how functional responses at gamma frequencies in electrophysiological
      recordings (EEG, MEG, ECoG, and LFP) should be classified and interpreted. In
      general, are all gamma responses the same, or should they be divided into
      different classes according to criteria such as their spectral characteristics
      (frequency range and/or shape), their spatial-temporal patterns of occurrence,
      and/or their responsiveness under different task conditions? In particular, are
      the responses observed in intracranial EEG at a broad range of "high gamma"
      frequencies (~60-200Hz) different from gamma responses observed at lower
      frequencies (~30-80Hz), typically in narrower bands? And if they are different,
      how should they be interpreted? Does the broad spectral shape of high gamma
      responses arise from the summation of many different narrow-band oscillations, or
      does it reflect something completely different? If we are not sure, should we
      refer to high gamma activity as oscillations? A variety of theories have posited
      a mechanistic role for gamma activity in cortical function, often assuming narrow
      band oscillations. These theories continue to influence the design of experiments
      and the interpretation of their results. Do these theories apply to all
      electrophysiological responses at gamma frequencies? Although no definitive
      answers to these questions are immediately anticipated, this paper will attempt
      to review the rationale for why they are worth asking and to point to some of the
      possible answers that have been proposed.

PMID- 21081145
TI  - Relationship between polymorphism of DC-SIGN (CD209) gene and the susceptibility
      to pulmonary tuberculosis in an eastern Chinese population.
AB  - Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin
      (DC-SIGN) is an important receptor for Mycobacterium tuberculosis on human
      dendritic cells. Previous studies have shown that the variation, especially the 
      871A/G and -336A/G in DC-SIGN promoter influenced the susceptibility to
      tuberculosis. We therefore investigated whether polymorphisms in the DC-SIGN gene
      were associated with susceptibility to tuberculosis in an eastern Chinese
      population. A total of 237 culture-positive pulmonary tuberculosis case patients
      and 244 controls were genotyped for -871A/G and -336A/G by pyrosequencing. Our
      results suggested that the 2 promoter variants of DC-SIGN gene were not
      associated with susceptibility to tuberculosis in Chinese. Further analysis
      showed that the allele -336G was associated with a protective effect against
      fever in pulmonary tuberculosis patients, but not against cavity formation. In
      addition, we compared the allelic frequencies of -871A/G and -336A/G in African,
      Caucasian, and Asian groups. The results showed that the tw forms of allelic
      frequencies detected Chinese individuals in our study were similar to the
      reported frequencies in other Asian populations but differed significantly from
      those in the African and Caucasian groups studied.

PMID- 21081146
TI  - Impact of Toll-like receptor 4 polymorphisms on risk of cancer.
AB  - Toll-like receptor 4 (TLR4) is one of the key immune system effectors playing the
      main role in recognition of viruses and bacteria. Dysregulation of the TLR4
      signaling owing to single nucleotide polymorphisms (SNPs) may alter the ligand
      binding and balance between pro- and anti-inflammatory cytokines, thereby
      modulating the risk of chronic inflammation and cancer. TLR4 polymorphisms may be
      associated with at least nine types of cancer. The most intensively investigating
      TLR4 polymorphisms are Asp299Gly (rs4986790) and Thr399Ile (rs4986791). It seems
      to be that Asp299Gly and Thr399Ile are related to increased risk of precancerous
      gastric lesions, and, possibly, gastric cancer. Thr399Ile also may be connected
      with gallbladder cancer, and both of these polymorphisms apparently have no
      impact on risk of prostate cancer. However, the data about many SNPs and their
      associations with different types of cancer are conflicting, and further large,
      well-designed, comprehensive studies in various populations are necessary for
      solution of this problem. The short list of TLR4 SNPs for further investigation
      may include TLR4_896A/G (Asp299Gly, rs4986790), TLR4_1196C/T (Thr399Ile,
      rs4986791), Thr135Ala, TLR4_1859 G/A (rs11536858), TLR4_2032T/C (rs10116253),
      TLR4_2437A/G (rs1927914), TLR4_2856T/C (rs10759932), TLR4_3725 G/C (rs11536889),
      TLR4_7764 G/A (rs1927911), TLR4_11350G/C, TLR4_11912 G/T (rs2149356),
      TLR4_16649G/C (rs7873784), and TLR4_17050T/C (rs11536891).

PMID- 21081147
TI  - Evidence for the involvement of mTOR inhibition and basal autophagy in familial
      Mediterranean fever phenotype.
AB  - Familial Mediterranean fever (FMF) inflammatory attacks are often triggered by
      metabolic or physical stress. mTOR signaling and autophagy modulate cellular
      responses to metabolic danger signals. In this study, we investigated the
      implication of mTOR inhibition and autophagy in FMF pathophysiology. mTOR
      inhibition induced MEFV gene expression in polymorphonuclear cells (PMNs) from
      healthy individuals, whereas it had no effect on PMNs from attack-free FMF
      patients. A significant reduction in pyrin levels in PMNs from FMF patients after
      mTOR inhibition was also observed. Pyrin levels in control PMNs remained
      unaffected. Moreover, the basal autophagic status in PMNs from FMF patients was
      reduced, as indicated by the lower LC3B-II/I ratio and ATG mRNA expression
      levels. However, mTOR inhibition had similar effects on the induction of
      autophagy in the two groups. The differential pyrin expression after metabolic
      stress induction and the impaired basal autophagy suggest a potential role in the
      triggering of FMF attacks.

PMID- 21081148
TI  - Antioxidant and anti-neoplastic activities of Picrorhiza kurroa extracts.
AB  - Picrorhizakurroa Royle ex Benth., a well-known traditional herb from the
      Scrophulariaceae family has a remarkable reputation among the indigenous medical
      practitioners. The antioxidant and anti-neoplastic activities of methanolic and
      aqueous extracts of P. kurroa rhizome were investigated in the present study. The
      total phenolic content was determined by a spectrophotometric method. The
      antioxidant efficacies of the extracts were studied employing radical scavenging
      assays (DPPH. and .OH), ferric reducing antioxidant property (FRAP) and
      thiobarbituric acid (TBA) assay for testing inhibition of lipid peroxidation.
      Furthermore, the cytotoxicity of the extracts was tested by XTT assay in MDA-MB
      435S (human breast carcinoma), Hep3B (human hepatocellular carcinoma) and PC-3
      (human prostate cancer) cell lines. The ability of the extracts to induce
      apoptosis was also investigated. Both extracts exhibited promising antioxidant
      potentials. The extracts were also observed to be cytotoxic at the tested dosage
      and were able to target cells towards apoptosis. The study concludes that P.
      kurroa possess diverse therapeutic potentials which might be useful in
      development of drugs or their precursors.

PMID- 21081149
TI  - Luteolin inhibits inflammatory response and improves insulin sensitivity in the
      endothelium.
AB  - Endothelial insulin resistance is tightly associated with diabetic cardiovascular
      complication, and it is well known that inflammation plays an important role in
      the development of insulin resistance. Luteolin, a flavonoid abundant in some
      medical and eatable plants, is a potent inhibitor of inflammation. It is also
      reported that luteolin exhibited some chemoprotection capability to the
      endothelial integrity. This study aims to clarify whether the anti-inflammatory
      potency of luteolin contributes to amelioration of insulin resistance in the
      endothelium. Palmitate (PA) stimulation markedly reduced insulin-mediated
      endothelium-dependent relaxation in rat aorta, while luteolin pretreatment
      effectively reversed the effects of palmitate in a concentration-dependent
      manner. PA stimulation also evoked inflammatory response in endothelial cells.
      When the cells were pretreated with luteolin, IKKbeta phosphorylation were
      reduced, which, in turn, blocked the NF-kappaB activation through attenuating P65
      phosphorylation. At the same time, it was also found that the gene over
      expressions for TNF-alpha and IL-6 were also reduced by luteolin pretreatment.
      When endothelial cells were stimulated with PA, the insulin signaling cascades
      were impaired with reduced insulin-dependent production of NO. Again,
      pretreatment of luteolin could effectively reverse the effects of PA. Luteolin
      modulated the Ser/Thr phosphorylation of insulin receptor substrates-1 and
      restored downstream Akt/eNOS activation, resulting in increased NO production in
      the presence of insulin. In conclusion, these results suggested that luteolin
      ameliorated inflammation related endothelial insulin resistance in an IKKbeta/IRS
      1/Akt/eNOS-dependent pathway.

PMID- 21081150
TI  - Pore-forming activity of BAD is regulated by specific phosphorylation and
      structural transitions of the C-terminal part.
AB  - BACKGROUND: BAD protein (Bcl-2 antagonist of cell death) belongs to the BH3-only
      subfamily of proapoptotic proteins and is proposed to function as the sentinel of
      the cellular health status. Physiological activity of BAD is regulated by
      phosphorylation, association with 14-3-3 proteins, binding to membrane lipids and
      pore formation. Since the functional role of the BAD C-terminal part has not been
      considered so far, we have investigated here the interplay of the structure and
      function of this region. METHODS: The structure of the regulatory C-terminal part
      of human BAD was analyzed by CD spectroscopy. The channel-forming activity of
      full-length BAD and BAD peptides was carried out by lipid bilayer measurements.
      Interactions between proteins and peptides were monitored by the surface plasmon
      resonance technique. In aqueous solution, C-terminal part of BAD exhibits a well
      ordered structure and stable conformation. In a lipid environment, the helical
      propensity considerably increases. The interaction of the C-terminal segment of
      BAD with the isolated BH3 domain results in the formation of permanently open
      pores whereby the phosphorylation of serine 118 within the BH3 domain is
      necessary for effective pore formation. In contrast, phosphorylation of serine 99
      in combination with 14-3-3 association suppresses formation of channels. C
      terminal part of BAD controls BAD function by structural transitions, lipid
      binding and phosphorylation. Conformational changes of this region upon membrane
      interaction in conjunction with phosphorylation of the BH3 domain suggest a novel
      mechanism for regulation of BAD. GENERAL SIGNIFICANCE: Multiple signaling
      pathways mediate inhibition and activation of cell death via BAD.

PMID- 21081151
TI  - Dual function of Zn2+ on the intrinsic excitability of dopaminergic neurons in
      rat substantia nigra.
AB  - Despite the presence of Zn(2+) in high levels in Parkinson brain, it is not yet
      clearly answered whether and how Zn(2+) alters the electrical activity of neurons
      in substantia nigra (SN). Here we show that Zn(2+) alters the intrinsic activity
      of nigral dopamine neurons in dual ways, that is, excitation or inhibition, by
      modulating the gating properties of a transient A-type K(+) (K(A)) channel.
      Depending on the holding potential, Zn(2+) could reduce or enhance a transient
      outward K(+) current (I(A)) in nigral dopamine neurons. Zn(2+) slowed the
      kinetics of both I(A) activation and inactivation with the rate of activation
      much more reduced than that of inactivation. Zn(2+) also increased the rate of
      release from I(A) inactivation. Both activation and inactivation I(A) curves were
      shifted by Zn(2+) towards positive potentials, but the positive shift of the
      inactivation curve was much greater than that of the activation curve. We propose
      that all these effects of Zn(2+) on K(A) channel gating properties underlie the
      dual mode of Zn(2+) action on I(A), that is, attenuation or potentiation
      depending on membrane potential. As a result, Zn(2+) increased a bursting
      activity of a nigral dopamine neuron elicited by anodal break excitation
      presumably through I(A) reduction at a hyperpolarizing state, whereas Zn(2+)
      decreased its tonic activity at either resting or depolarizing states where I(A)
      was increased. This was further supported by the observations that 4
      aminopyridine (4-AP), a well-known K(A) channel blocker, strengthened or
      counteracted the effect of Zn(2+) on the intrinsic excitability of nigral
      dopamine neurons.

PMID- 21081152
TI  - Expression of vesicular glutamate transporters in peripheral vestibular
      structures and vestibular nuclear complex of rat.
AB  - Glutamate transmission from vestibular end organs to central vestibular nuclear
      complex (VNC) plays important role in transferring sensory information about head
      position and movements. Three isoforms of vesicular glutamate transporters
      (VGLUTs) have been considered so far the most specific markers for glutamatergic
      neurons/cells. In this study, VGLUT1 and VGLUT2 were immunohistochemically
      localized to axon terminals in VNC and somata of vestibular primary afferents in
      association with their central and peripheral axon endings, and VGLUT1 and VGLUT3
      were co-localized to hair cells of otolith maculae and cristae ampullaris. VGLUT1
      and VGLUT2 defined three subsets of Scarpa's neurons (vestibular ganglionic
      neurons): those co-expressing VGLUT1 and VGLUT2 or expressing only VGLUT2, and
      those expressing neither. In addition, many neurons located in all vestibular
      subnuclei were observed to contain hybridized signals for VGLUT2 mRNA and a few
      VNC neurons, mostly scattered in medial vestibular nucleus (MVe), displayed
      VGLUT1 mRNA labelling. Following unilateral ganglionectomy, asymmetries of VGLUT1
      immunoreactivity (ir) and VGLUT2-ir occurred between two VNCs, indicating that
      the VNC terminals containing VGLUT1 and/or VGLUT2 are partly of peripheral
      origin. The present data indicate that the constituent cells/neurons along the
      vestibular pathway selectively apply VGLUT isoforms to transport glutamate into
      synaptic vesicles for glutamate transmission.

PMID- 21081153
TI  - Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage
      in experimental autoimmune encephalomyelitis mouse.
AB  - Oxidative stress is considered a major contributor in the pathology of multiple
      sclerosis (MS). Acrolein, a highly reactive aldehyde byproduct of lipid
      peroxidation, is thought to perpetuate oxidative stress. In this study, we aimed
      to determine the role of acrolein in an animal model of MS, experimental
      autoimmune encephalomyelitis (EAE) mice. We have demonstrated a significant
      elevation of acrolein protein adduct levels in EAE mouse spinal cord.
      Hydralazine, a known acrolein scavenger, significantly improved behavioral
      outcomes and lessened myelin damage in spinal cord. We postulate that acrolein is
      an important pathological factor and likely a novel therapeutic target in MS.

PMID- 21081154
TI  - Importance of genetic background for risk of relapse shown in altered prefrontal
      cortex gene expression during abstinence following chronic alcohol intoxication.
AB  - Alcoholism is a relapsing disorder associated with excessive consumption after
      periods of abstinence. Neuroadaptations in brain structure, plasticity and gene
      expression occur with chronic intoxication but are poorly characterized. Here we
      report identification of pathways altered during abstinence in prefrontal cortex,
      a brain region associated with cognitive dysfunction and damage in alcoholics. To
      determine the influence of genetic differences, an animal model was employed with
      widely divergent responses to alcohol withdrawal, the Withdrawal Seizure
      Resistant (WSR) and Withdrawal Seizure-Prone (WSP) lines. Mice were chronically
      exposed to highly intoxicating concentrations of ethanol and withdrawn, then left
      abstinent for 21 days. Transcriptional profiling by microarray analyses
      identified a total of 562 genes as significantly altered during abstinence.
      Hierarchical cluster analysis revealed that the transcriptional response
      correlated with genotype/withdrawal phenotype rather than sex. Gene Ontology
      category overrepresentation analysis identified thyroid hormone metabolism,
      glutathione metabolism, axon guidance and DNA damage response as targeted classes
      of genes in low response WSR mice, with acetylation and histone deacetylase
      complex as highly dimorphic between WSR and WSP mice. Confirmation studies in WSR
      mice revealed both increased neurotoxicity by histopathologic examination and
      elevated triidothyronine (T3) levels. Most importantly, relapse drinking was
      reduced by inhibition of thyroid hormone synthesis in dependent WSR mice compared
      to controls. These findings provide in vivo physiological and behavioral
      validation of the pathways identified. Combined, these results indicate a
      fundamentally distinct neuroadaptive response during abstinence in mice
      genetically selected for divergent withdrawal severity. Identification of
      pathways altered in abstinence may aid development of novel therapeutics for
      targeted treatment of relapse in abstinent alcoholics.

PMID- 21081155
TI  - Glial cell line-derived neurotrophic factor protein content in rat skeletal
      muscle is altered by increased physical activity in vivo and in vitro.
AB  - Current evidence suggests that exercise and glial cell line-derived neurotrophic
      factor (GDNF) independently cause significant morphological changes in the
      neuromuscular system. The aim of the current study was to determine if increased
      physical activity regulates GDNF protein content in rat skeletal muscle. Extensor
      Digitorum Longus (EDL) and Soleus (SOL) hind limb skeletal muscles were analyzed
      following 2 weeks of involuntary exercise and 4 h of field stimulation or stretch
      in muscle bath preparations. GDNF protein content was measured via enzyme-linked
      immunosorbent assay (ELISA). Two weeks of exercise increased GDNF protein content
      in SOL as compared to sedentary controls (4.4+/-0.3 pg GDNF/mg tissue and 3.1+/
      0.6 pg GDNF/mg tissue, respectively) and decreased GDNF protein content in EDL as
      compared to controls (1.0+/-0.1 pg GDNF/mg tissue and 2.3+/-0.7 pg GDNF/mg
      tissue, respectively). GDNF protein content in the EDL decreased following both
      field stimulation (56%+/-18% decrease from controls) and stretch (66%+/-10%
      decrease from controls). SOL responded to field stimulation with a 38%+/-7%
      increase from controls in GDNF protein content, but showed no change following
      stretch. Pre-treatment with alpha-bungarotoxin abolished the effects of field
      stimulation in both muscles and blocked the effect of stretch in EDL. alpha
      bungarotoxin pre-treatment and stretch increased GDNF protein content to 240%+/
      10% of controls in the SOL. Exposure to carbamylcholine decreased GDNF protein
      content to 51%+/-28% of controls in the EDL but not SOL. These results suggest
      that GDNF protein content in skeletal muscle may be controlled by stretch, where
      it may increase GDNF protein content, and membrane depolarization/acetylcholine
      (ACh) which acts to decrease GDNF protein content.

PMID- 21081156
TI  - Lipopolysaccharide-stimulated interleukin-10 release from neonatal spinal cord
      microglia is potentiated by glutamate.
AB  - Interleukin-10 (IL-10) is a cytokine with important endogenous and therapeutic
      anti-inflammatory effects. Given this, it is of interest to investigate factors
      that modulate IL-10 levels in the central nervous system. IL-10 is released after
      lipopolysaccharide (LPS) stimulation of microglia. Microglia also express
      functional glutamate receptors and in inflammatory conditions are exposed to
      increased levels of glutamate. The aim of this research, then, is to investigate
      whether glutamate can modulate lipopolysaccharide stimulation of IL-10 release
      from neonatal rat spinal cord microglia. Enzyme-linked immunosorbent assays
      (ELISAs) were used to quantify IL-10 release from cultured neonatal spinal cord
      microglia and reverse transcriptase-polymerase chain reaction (RT-PCR) was used
      to measure IL-10 mRNA expression. Glutamate (1 mM) significantly increased LPS (1
      MUg/ml)-stimulated IL-10 release from microglia by 172% (EC(50) of 103 MUM) and
      significantly upregulated IL-10 mRNA levels. Glutamate potentiated LPS-stimulated
      IL-10 release by binding all subtypes of glutamate receptor. These results show
      that glutamate substantially increases the release of an anti-inflammatory
      cytokine from neonatal spinal cord microglia activated by a high concentration of
      LPS.

PMID- 21081157
TI  - Localization, pharmacology, and organization of brain locomotor areas in larval
      lamprey.
AB  - In larval lamprey, spinal locomotor activity can be initiated by pharmacological
      microstimulation from the following higher order brain locomotor areas [Paggett
      et al. (2004) Neuroscience 125:25-33; Jackson et al. (2007) J Neurophysiol
      97:3229-3241]: rostrolateral rhombencephalon (RLR); ventromedial diencephalon
      (VMD); or dorsolateral mesencephalon (DLM). In the present study, pharmacological
      microstimulation with excitatory amino acids (EAAs) or their agonists in the
      brains of in vitro brain/spinal cord preparations was used to determine the
      sizes, pharmacology, and organization of these locomotor areas. First, the RLR,
      DLM and VMD locomotor areas were confined to relatively small areas of the brain,
      and stimulation as little as 50 MUm outside these areas was ineffective or
      elicited tonic or uncoordinated motor activity. Second, pharmacological
      stimulation with NMDA, kainate, or AMPA in the VMD or DLM reliably initiated well
      coordinated spinal locomotor activity. In the RLR, stimulation with all three
      ionotropic EAA receptor agonists could initiate spinal locomotor activity, but
      NMDA or AMPA was more reliable than kainate. Third, with synaptic transmission
      blocked only in the brain, stimulation in the RLR, VMD, or DLM no longer
      initiated spinal locomotor activity, suggesting that these locomotor areas do not
      directly activate spinal locomotor networks. Fourth, following a complete
      transection at the mesencephalon-rhombencephalon border, stimulation in the RLR
      no longer initiated spinal motor activity. Thus, the RLR locomotor area does not
      appear able to initiate spinal locomotor activity by neural circuits confined
      entirely within the rhombencephalon but requires more rostral neural centers,
      such as those in the VMD and DLM, as previously proposed [Paggett et al. (2004)
      Neuroscience 125:25-33].

PMID- 21081158
TI  - Effect of chronic pain on morphine-induced respiratory depression in mice.
AB  - Respiratory depression is the most well-known and dangerous side-effect of opioid
      analgesics. Clinical investigations have revealed that this opioid-induced
      respiratory depression is less severe in patients with chronic pain, but the
      mechanisms that underlie this phenomenon are unknown. Therefore, the present
      study was designed to examine the influence of chronic pain on morphine-induced
      respiratory depression. Respiration was detected by double-chamber, flow-through
      whole-body plethysmography. Respiratory frequency was dose-dependently and
      significantly decreased after morphine administration. This effect peaked at 30
      min after administration and lasted 3 h. In contrast, tidal volume was increased.
      Minute volume was significantly decreased by morphine at a higher dose, but not a
      lower dose. In nerve-ligated mice, a morphine-induced decrease in respiratory
      frequency was observed, whereas the increase of tidal volume was more prominent.
      A decrease in minute volume was not observed in nerve-ligated mice. This
      attenuation of the morphine-induced decrease in minute volume in nerve-ligated
      mice was reversed by treatment with the serotonin (5-HT)4a receptor antagonist
      GR125487. Moreover, treatment with the 5-HT4 receptor agonist mosapride
      antagonized the morphine-induced decrease in minute volume, due to the
      enhancement of tidal volume. Finally, the expression of 5-HT4a receptor in the
      brainstem was enhanced in nerve-ligated mice compared to that in sham-operated
      mice. These results suggest that the decrease in morphine-induced respiratory
      depression under chronic pain is mediated by the enhancement of 5-HT4a receptor
      systems in the brainstem.

PMID- 21081159
TI  - Fenofibrate exhibits a high potential to suppress the formation of squamous cell
      carcinoma in an oral-specific 4-nitroquinoline 1-oxide/arecoline mouse model.
AB  - The excessive use of areca nut and/or tobacco may induce the production of free
      radicals and reactive oxygen species, which affect the lipid contents of the cell
      membrane and are possibly involved in tumorigenic processes in the oral cavity.
      The aim of this study was to investigate the therapeutic efficacy of fenofibrate
      (0.1% or 0.3%, w/w), a ligand of the peroxisome proliferator-activated receptor
      alpha (PPARalpha), in a 4-nitroquinoline 1-oxide (4-NQO)/arecoline-induced oral
      cancer mouse model. The carcinogen, 4-NQO/arecoline, was administrated to
      C57BL/6JNarl mice for 8weeks followed by fenofibrate treatment for 12 or 20weeks.
      After 28weeks, changes in serum lipids, the multiplicity of tumor lesions, and
      tumor sizes were determined together with changes in the immunohistochemical
      expressions of PPARalpha, acetyl-coenzyme A carboxylase (ACC), the epidermal
      growth factor receptor (EGFR), and cyclooxygenase-2 (COX2). The results showed
      that when compared to the 4-NQO/arecoline only group, 0.3% fenofibrate treatment
      increased serum total cholesterol, low-density lipoprotein cholesterol (LDL-C),
      and high-density lipoprotein cholesterol (HDL-C) levels. 0.3% fenofibrate
      treatment suppressed the incidence rate of tongue lesions, reduced the
      multiplicity of squamous cell carcinoma (SCC), decreased the tumor size, and
      increased the immunoreactivity of EGFR and COX2 in oral dysplasia but decreased
      EGFR and COX2 expressions in SCC. These findings indicated that fenofibrate
      reduced the tumor incidence rate and suppressed the tumor progression into SCC
      and that these molecular events might be linked to the EGFR and COX2 regulatory
      pathways. We suggest that fenofibrate provides a new strategy for preventing oral
      tumor progression.

PMID- 21081160
TI  - The consequence of the chemical composition of HPMC in matrix tablets on the
      release behaviour of model drug substances having different solubility.
AB  - This study investigates the effect of the chemical heterogeneity of hydroxypropyl
      methylcellulose (HPMC) on the release of model drug substances from hydrophilic
      matrix tablets. The hypothesis was that the release of drug substances could be
      influenced by possible interactions with HPMC batches having different chemical
      heterogeneity. The cloud point of the most heterogeneous batch was more affected
      by the model drug substances, methylparaben and butylparaben, and most by
      butylparaben with the lowest solubility. The different clouding behaviour was
      explained by the heterogeneously substituted batches being more associative and
      the more lipophilic butylparaben being able to interact more efficiently with the
      hydrophobic HPMC transient crosslinks that formed. Interestingly, tablet
      compositions of the heterogeneously substituted HPMC batches released the more
      soluble methylparaben at lower rates than butylparaben. The explanation is that
      the hydrophobic HPMC interactions with butylparaben made the gel of the tablet
      less hydrated and more fragile and therefore more affected by erosional stresses.
      In contrast, drug release from compositions consisting of the more homogeneously
      substituted batches was affected to a minor extent by the drugs and was very
      robust within the experimental variations. The present study thus reveals that
      there can be variability in drug release depending on the lipophilicity of the
      drug and the substituent heterogeneity of the HPMC used.

PMID- 21081161
TI  - Stable dry powder inhaler formulation of tranilast attenuated antigen-evoked
      airway inflammation in rats.
AB  - Tranilast (TL) has been clinically used for the treatment of airway inflammatory
      diseases, although the clinical use of TL is limited because of its poor
      solubility and systemic side effects. To overcome these drawbacks, a novel
      respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using
      nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was
      carried out with a focus on inhalation performance. Even after 6 months of
      storage at room temperature, there were no significant morphological changes in
      micronized particles on the surface of carrier particles as compared with that
      before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high
      inhalation performance with emitted dose and fine particle fraction (FPF) of ca.
      98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a
      slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen
      induced inflammatory events in rats, as evidenced by marked reduction of
      granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as
      eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings
      were consistent with decreased expression levels of mRNAs for nuclear factor
      kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these
      findings, inhalable TL formulation might be an interesting alternative to oral
      therapy for the treatment of asthma and other airway inflammatory diseases with
      sufficient dispersing stability.

PMID- 21081163
TI  - Broadening our horizons: gene expression profiling to help better understand the
      neurobiology of suicide and depression.
AB  - The complexity of the neurobiological alterations underlying major depression and
      suicide is significant. Gene expression studies using high-throughput genomic
      technologies have provided important insight into novel genes and pathways
      displaying alterations associated with major depression and suicide, thereby
      providing a global view of the pathological changes taking place, as well as
      indicating potential new targets for therapeutic interventions. This review
      discusses the methodologies which have been used to profile gene expression
      patterns in depression and suicide, as well as examines several of the metabolic
      pathways which have been frequently implicated by studies using this approach.
      Future directions to be taken towards increasing our understanding of the origin
      and downstream effects of altered gene expression are also discussed.

PMID- 21081162
TI  - Animal models of dystonia: Lessons from a mutant rat.
AB  - Dystonia is a motor sign characterized by involuntary muscle contractions which
      produce abnormal postures. Genetic factors contribute significantly to primary
      dystonia. In comparison, secondary dystonia can be caused by a wide variety of
      metabolic, structural, infectious, toxic and inflammatory insults to the nervous
      system. Although classically ascribed to dysfunction of the basal ganglia,
      studies of diverse animal models have pointed out that dystonia is a network
      disorder with important contributions from abnormal olivocerebellar signaling. In
      particular, work with the dystonic (dt) rat has engendered dramatic paradigm
      shifts in dystonia research. The dt rat manifests generalized dystonia caused by
      deficiency of the neuronally restricted protein caytaxin. Electrophysiological
      and biochemical studies have shown that defects at the climbing fiber-Purkinje
      cell synapse in the dt rat lead to abnormal bursting firing patterns in the
      cerebellar nuclei, which increases linearly with postnatal age. In a general
      sense, the dt rat has shown the scientific and clinical communities that dystonia
      can arise from dysfunctional cerebellar cortex. Furthermore, work with the dt rat
      has provided evidence that dystonia (1) is a neurodevelopmental network disorder
      and (2) can be driven by abnormal cerebellar output. In large part, work with
      other animal models has expanded upon studies in the dt rat and shown that
      primary dystonia is a multi-nodal network disorder associated with defective
      sensorimotor integration. In addition, experiments in genetically engineered
      models have been used to examine the underlying cellular pathologies that drive
      primary dystonia. This article is part of a Special Issue entitled "Advances in
      dystonia".

PMID- 21081164
TI  - Depletion of Beclin-1 due to proteolytic cleavage by caspases in the Alzheimer's
      disease brain.
AB  - The Beclin-1 protein is essential for the initiation of autophagy, and recent
      studies suggest this function may be compromised in Alzheimer's disease (AD). In
      addition, in vitro studies have supported a loss of function of Beclin-1 due to
      proteolytic modification by caspases. In the present study, we examined whether
      caspase-cleavage of Beclin-1 occurs in the AD brain by designing a site-directed
      caspase-cleavage antibody based upon a known cleavage site within the protein at
      position D149. We confirmed that Beclin-1 is an excellent substrate for caspase-3
      and demonstrates cleavage led to the formation of a 35-kDa C-terminal fragment
      labeled by our novel antibody following Western blot analysis. Application of
      this antibody termed Beclin-1 caspase-cleavage product antibody or BeclinCCP in
      frontal cortex tissue sections revealed strong immunolabeling within astrocytes
      that localized with plaque regions and along blood vessels in all AD cases
      examined. In addition, weaker, more variable BeclinCCP labeling was also observed
      within neurofibrillary tangles that colocalized with the early tau conformational
      marker, MC-1 as well as the late tangle marker, PHF-1. Collectively, these data
      support a depletion of Beclin-1 in AD following caspase-cleavage. This article is
      part of a Special Issue entitled "Autophagy and protein degradation in
      neurological diseases."

PMID- 21081166
TI  - Possible role of DMP1 in dentin mineralization.
AB  - Dentin Matrix Protein 1 (DMP1), the essential noncollagenous proteins in dentin
      and bone, is believed to play an important role in the mineralization of these
      tissues, although the mechanisms of its action are not fully understood. To gain
      insight into DMP1 functions in dentin mineralization we have performed
      immunomapping of DMP1 in fully mineralized rat incisors and in vitro calcium
      phosphate mineralization experiments in the presence of DMP1. DMP1
      immunofluorescene was localized in peritubular dentin (PTD) and along the dentin
      enamel boundary. In vitro phosphorylated DMP1 induced the formation of parallel
      arrays of crystallites with their c-axes co-aligned. Such crystalline arrangement
      is a hallmark of mineralized collagen fibrils of bone and dentin. Interestingly,
      in DMP1-rich PTD, which lacks collagen fibrils, the crystals are organized in a
      similar manner. Based on our findings we hypothesize, that in vivo DMP1 controls
      the mineral organization outside of the collagen fibrils and plays a major role
      in the mineralization of PTD.

PMID- 21081167
TI  - The organization of the osteocyte network mirrors the extracellular matrix
      orientation in bone.
AB  - Bone is a dynamic tissue that is continually undergoing a process of remodeling -
      an effect due to the interplay between bone resorption by osteoclasts and bone
      formation by osteoblasts. When new bone is deposited, some of the osteoblasts are
      embedded in the mineralizing collagen matrix and differentiate to osteocytes,
      forming a dense network throughout the whole bone tissue. Here, we investigate
      the extent to which the organization of the osteocyte network controls the
      collagen matrix arrangement found in various bone tissues. Several tissue types
      from equine, ovine and murine bone have been examined using confocal laser
      scanning microscopy as well as polarized light microscopy and back-scattered
      electron imaging. From comparing the spatial arrangements of unorganized and
      organized bone, we propose that the formation of a highly oriented collagen
      matrix requires an alignment of osteoblasts whereby a substrate layer provides a
      surface such that osteoblasts can align and, collectively, build new matrix.
      Without such a substrate, osteoblasts act isolated and only form matrices without
      long range order. Hence, we conclude that osteoblasts synthesize and utilize
      scaffold-like primary tissue as a guide for the deposition of highly ordered and
      mechanically competent bone tissue by a collective action of many cells.

PMID- 21081165
TI  - Monocarboxylate transporter 1 is deficient on microvessels in the human
      epileptogenic hippocampus.
AB  - Monocarboxylate transporter 1 (MCT1) facilitates the transport of important
      metabolic fuels (lactate, pyruvate and ketone bodies) and possibly also acidic
      drugs such as valproic acid across the blood-brain barrier. Because an impaired
      brain energy metabolism and resistance to antiepileptic drugs are common features
      of temporal lobe epilepsy (TLE), we sought to study the expression of MCT1 in the
      brain of patients with this disease. Immunohistochemistry and immunogold electron
      microscopy were used to assess the distribution of MCT1 in brain specimens from
      patients with TLE and concomitant hippocampal sclerosis (referred to as mesial
      TLE or MTLE (n=15)), patients with TLE and no hippocampal sclerosis (non-MTLE,
      n=13) and neurologically normal autopsy subjects (n=8). MCT1 was present on an
      extensive network of microvessels throughout the hippocampal formation in autopsy
      controls and to a lesser degree in non-MTLE. Patients with MTLE were markedly
      deficient in MCT1 on microvessels in several areas of the hippocampal formation,
      especially CA1, which exhibited a 37% to 48% loss of MCT1 on the plasma membrane
      of endothelial cells when compared with non-MTLE. These findings suggest that the
      uptake of blood-derived monocarboxylate fuels and possibly also acidic drugs,
      such as valproic acid, is perturbed in the epileptogenic hippocampus,
      particularly in MTLE. We hypothesize that the loss of MCT1 on brain microvessels
      is mechanistically involved in the pathophysiology of drug-resistant TLE, and
      propose that re-expression of MCT1 may represent a novel therapeutic approach for
      this disease.

PMID- 21081168
TI  - Crystal structure of FabG4 from Mycobacterium tuberculosis reveals the importance
      of C-terminal residues in ketoreductase activity.
AB  - Rv0242c, also known as FabG4, is a beta-ketoacyl CoA reductase in Mycobacterium
      tuberculosis. The crystal structure of C-terminal truncated FabG4 is solved at
      2.5A resolution which shows the presence of two distinct domains, domain I and
      II. Domain I partially resembles "flavodoxin type domain" and the domain II is a
      typical "ketoacyl CoA reductase (KAR) domain". The enzyme exhibits ketoacyl CoA
      reductase activity by reducing acetoacyl CoA to 3-hydroxyacyl CoA in presence of
      NADH. Conserved catalytic triad Ser347, Tyr360, and Lys364 constitute the active
      site residues of the KAR domain. Presence of the Tyr and the Lys residues in the
      triad in a particular orientation is imperative for effective catalytic
      mechanism. The importance of loop I and II and the role of the C-terminal
      residues of KAR domain are highlighted. Comparative structural analyses clearly
      demonstrate that loop II is stabilized by hydrophobic interaction with C-terminal
      residues to sustain the orientation of Tyr360. Loop I interacts with loop II via
      H-bonding network to restrict the active site residue Lys364 in a catalytically
      favorable orientation.

PMID- 21081169
TI  - Dynamic, semi-quantitative imaging of intracellular ROS levels and redox status
      in rat hippocampal neurons.
AB  - The cellular redox status is determined by various extra- and intracellular
      factors, and contributes to cytosolic signaling and oxidative stress. Especially
      mitochondria modulate the cytosolic redox status by oxidizing NADH and FADH(2)
      and generating reactive oxygen species (ROS). Whereas cellular NADH and FAD
      levels are reliably detectable as autofluorescence, quantifying cellular ROS
      production is more demanding, because the various redox-sensitive dyes share
      major disadvantages including irreversible oxidation, autooxidation and
      photosensitivity. As an alternative, we took advantage of a genetically
      engineered redox-sensitive green fluorescent protein (roGFP1), carefully
      evaluated its response properties, and succeeded to monitor ROS dynamics in
      cultured rat hippocampal neurons and organotypic slices. The ratiometric
      properties and reversible oxidation/reduction of roGFP1 enable reliable, semi
      quantitative analyses of cytosolic ROS levels and redox status. Cytosolically
      expressed roGFP1 readily responded to hydrogen peroxide, superoxide and hydroxyl
      radicals, and was only negligibly affected by intracellular pH or Cl(-) content.
      Furthermore, roGFP1 was well suited for two-photon excitation, reliably detected
      changes in endogenous ROS production during impaired mitochondrial respiration or
      neuronal stimulation, and was even capable of visualizing perimitochondrial ROS
      microdomains. Modulation of cellular scavenging systems confirmed the functional
      integration of roGFP1 into the cellular ROS and redox balance. We conclude that
      roGFP1 is well suited for dynamic, compartment specific, subcellular analyses
      even in complex neuronal networks. The ability to correlate dynamic changes in
      cellular ROS levels with mitochondrial metabolism and neuronal network activity
      is a promising step towards a detailed mechanistic understanding of redox- and
      ROS-mediated signaling in normal and diseased brain function.

PMID- 21081170
TI  - Evidence for a general face salience signal in human amygdala.
AB  - In the social neuroscience of face processing, multiple roles are attributed to
      amygdala: signalling of fear/threat-stimuli, of emotional expression, and general
      salience. The current study aimed at a direct comparison of amygdala activation
      attributable to these conditions by contrasting amygdala responses to matched
      emotional (threatening and non-threatening) and of non-emotional salient faces in
      a visual search paradigm using cartoon faces. Participants (21 healthy
      volunteers) had to detect a target face (angry, happy, blue, red, differing in
      the exact same features) in an array of closely matched non-target faces.
      Behavioural results revealed a pop-out effect for all targets compared to non
      targets, indicating that they were all salient, independently of being emotional
      or non-emotional. While significant amygdala activation was obtained for all
      trials with salient faces (compared to those containing only non-target faces),
      no significant differences in activation emerged between emotional threatening,
      emotional non-threatening, and non-emotional targets. Moreover, right and left
      amygdala activation for target trials was found correlated to the behavioural
      measure of target detection. These findings provide evidence for a general role
      of the amygdala in signalling salience in a visual search independent of
      modality. Given the critical involvement of the amygdala in several
      neuropsychiatric disorders, the current findings may contribute to further our
      understanding on dysfunctional neural circuits in these disorders.

PMID- 21081171
TI  - Evidence for a motor and a non-motor domain in the human dentate nucleus--an fMRI
      study.
AB  - Dum and Strick (J. Neurophysiol. 2003; 89, 634-639) proposed a division of the
      cerebellar dentate nucleus into a "motor" and "non-motor" area based on
      anatomical data in the monkey. We asked the question whether motor and non-motor
      domains of the dentate can be found in humans using functional magnetic resonance
      imaging (fMRI). Therefore dentate activation was compared in motor and cognitive
      tasks. Young, healthy participants were tested in a 1.5 T MRI scanner. Data from
      13 participants were included in the final analysis. A block design was used for
      the experimental conditions. Finger tapping of different complexities served as
      motor tasks, while cognitive testing included a verbal working memory and a
      visuospatial task. To further confirm motor-related dentate activation, a simple
      finger movement task was tested in a supplementary experiment using ultra
      highfield (7 T) fMRI in 23 participants. For image processing, a recently
      developed region of interest (ROI) driven normalization method of the deep
      cerebellar nuclei was used. Dorso-rostral dentate nucleus activation was
      associated with motor function, whereas cognitive tasks led to prominent
      activation of the caudal nucleus. The visuospatial task evoked activity
      bilaterally in the caudal dentate nucleus, whereas verbal working memory led to
      activation predominantly in the right caudal dentate. These findings are
      consistent with Dum and Strick's anatomical findings in the monkey.

PMID- 21081172
TI  - Multiple unrelated founding events for the long-distance Pleistocene dispersal of
      the Salangid, Neosalanx taihuensis: a general demographic model for inshore
      orientated freshwater fish.
AB  - The Salangid icefish Neosalanx taihuensis (Salangidae) originated from inshore of
      the East China seas and underwent adaptive freshwater radiation from the mid
      Miocene to the early Pleistocene. The distribution of its genetic diversity
      presents a random pattern inconsistent with contemporary hydrological structure.
      In the present study, coalescent simulations were used to analyze its Pleistocene
      dispersal history. Population history simulation supported the hypothesis of long
      distance dispersal during the Pleistocene based on multiple unrelated founding
      events. This analogous genetic pattern has been described for other inshore
      orientated freshwater fish, and may represent a general history dispersal model
      for the phylogeography of these species. From network analysis, three subclades
      (Clades 1-3) grouped consistently with three probable ancestral haplotypes (H36,
      H27, and H33). Demographic analysis also revealed that the ancestral haplotype
      group (Clade 1) dispersed into freshwater during an interglacial age about
      0.35Ma, while Clades 2 and 3 dispersed about 0.12 and 0.145Ma, respectively. The
      N. taihuensis population remained relatively small for a considerable amount of
      time during the Pleistocene ages, with population expansion events mainly
      occurring after the last glacial maximum (LGM).

PMID- 21081174
TI  - Development of an immunochromatographic strip for the rapid detection of
      Toxoplasma gondii circulating antigens.
AB  - We developed a rapid immunochromatographic strip (ICS) procedure that can detect
      circulating antigens in the blood of animals during the acute stage of
      toxoplasmosis. The aim of this study was to evaluate this test using sera from
      field samples and from experimentally infected animals. The sensitivity and
      specificity of the ICS were compared with those of an enzyme-linked immunosorbent
      assay (ELISA). Both assays detected circulating antigens in the sera of animals
      experimentally infected with the Gansu Jingtai strain of Toxoplasma gondii, and
      the agreement between the two assays was 100%. In the infected animals,
      circulating antigens could be detected as early as the second day post-infection
      (PI) and in all animals by the fourth day. In the 381 field serum samples, the
      positive rates of the ICS and ELISA were 5.2% and 5.8%, respectively. In
      addition, there was no cross-reactivity of the antigens with Neospora caninum.
      The results presented here suggest that the ICS is a feasible, convenient, rapid
      and effective method to detect infection by T. gondii. This test could be a
      powerful supplement to the current diagnostic methods. Taken together, the
      results of this study encourage further research toward the production of
      commercial diagnostic tests for detecting T. gondii in animals.

PMID- 21081173
TI  - Ovarian hormones, aging and stress on hippocampal synaptic plasticity.
AB  - The ovarian steroid hormones estradiol and progesterone regulate a wide variety
      of non-reproductive functions in the central nervous system by interacting with
      molecular and cellular processes. A growing literature from studies using rodent
      models suggests that 17beta-estradiol, the most potent of the biologically
      relevant estrogens, enhances synaptic transmission and the magnitude of long-term
      potentiation recorded from in vitro hippocampal slices. In contrast, progesterone
      has been shown to decrease synaptic transmission and reduce hippocampal long-term
      potentiation in this model system. Hippocampal long-term depression, another form
      of synaptic plasticity, occurs more prominently in slices from aged rats. A
      decrease in long-term potentiation magnitude has been recorded in hippocampal
      slices from both adult and aged rats behaviorally stressed just prior to
      hippocampal slice tissue preparation and electrophysiological recording. 17beta
      estradiol modifies synaptic plasticity in both adult and aged rats, whether
      behaviorally stressed or not by enhancing long-term potentiation and attenuating
      long-term depression. The studies discussed in this review provide an
      understanding of new approaches used to investigate the protective effects of
      ovarian hormones against aging and stress, and how these hormones impact age and
      stress-related learning and memory dysfunction.

PMID- 21081175
TI  - First report of human infection with Gynaecotyla squatarolae and first Korean
      record of Haplorchis pumilio in a patient.
AB  - Gynaecotyla squatarolae (Digenea: Microphallidae) is a minute intestinal
      trematode whose natural hosts are aves. We conducted a feces screening survey in
      a coastal village of Muan-gun, where the residents routinely consume brackish
      water crabs as a food. Through this survey, a 50-year-old female was found to
      shed gymnophallid and heterophyid eggs in her stool, and 845 adult flukes were
      collected from her purged stool. The adult worms were morphologically grouped
      into three species. A total of 841 worms were Gymnophalloides seoi. Three worms
      were identified as G. squatarolae, and the last one proven to be Haplorchis
      pumilio. This is the first worldwide report of G. squatarolae infection in
      humans, and the first H. pumilio infection in Korean people.

PMID- 21081176
TI  - Sphingolipid profiling of human plasma and FPLC-separated lipoprotein fractions
      by hydrophilic interaction chromatography tandem mass spectrometry.
AB  - Sphingolipids comprise bioactive molecules which are known to play important
      roles both as intracellular and extracellular signalling molecules. Here we used
      a previously developed hydrophilic interaction chromatography tandem mass
      spectrometry (HILIC-MS/MS) method to profile plasma sphingolipids. Method
      validation showed sufficient precision and sensitivity for application in large
      clinical studies. Sample stability testing demonstrated that immediate plasma
      separation is important to achieve reliable results. Analysis of plasma from 25
      healthy blood donors revealed a comprehensive overview of free sphingoid base,
      sphingosylphosphorylcholine (SPC), hexosylceramide (HexCer), lactosylceramide
      (LacCer), and ceramide-1-phosphate (Cer1P) species level. Besides the major
      sphingoid base sphingosine (d18:1), we found d16:1 and d18:2 species in most of
      these lipid classes. Interestingly, pronounced differences were detected in the
      species profiles of HexCer and LacCer. Additionally, sphingolipids were
      quantified in lipoprotein fractions prepared by fast performance liquid
      chromatography (FPLC). HexCer and LacCer showed similar distributions with about
      50% in LDL, 40% in HDL and less than 10% in the VLDL fraction. More than 90% of
      sphingoid base phosphates were found in HDL and albumin containing fractions. In
      summary, HILIC-MS/MS provides a valuable tool to profile minor sphingolipid
      species in plasma and in lipoprotein fractions. Comparing profiles from tissues
      or blood cells, these species profiles may help to address the origin of plasma
      sphingolipids.

PMID- 21081177
TI  - Differential regulation of human apolipoprotein AI and high-density lipoprotein
      by fenofibrate in hapoAI and hapoAI-CIII-AIV transgenic mice.
AB  - Fenofibrate, a PPAR-alpha agonist, lowers triglycerides (TG) and raises high
      density lipoproteins (HDL-C) in humans. While fenofibrate is very effective in
      lowering TG, it does not raise HDL-C in humans to the same extent as seen in
      human apoAI transgenic (hAI-Tg) mice. We studied the mechanism of this
      discordance using the following compounds as tools: cholic acid that down
      regulates human apoAI, and fenofibrate, that elevates hapoAI and HDL-C in hAI-Tg
      mice. We hypothesized that additional sequences, including apoCIII and AIV genes
      on chromosome 11, not present in the hapoAI transgene may be responsible for the
      dampened effect of fibrates on HDL-C seen in humans. For this, hAI-Tg mice with
      11kb DNA segment and hapoAI-CIII-AIV-Tg mice with 33kb DNA segment harboring
      apoCIII and AIV genes were employed. These mice were treated with fenofibrate and
      cholic acid. Fenofibrate increased apoAI and HDL-C levels, and HDL size in the
      apoAI-Tg mice via up-regulation of the hapoAI mRNA and increased activity and
      mRNA of PLTP, respectively. Consistent with earlier findings, cholic acid showed
      similar effects of lowering HDL-C, and elevating LDL-C in hAI-Tg mice as well as
      in the hAI-CIII-AIV-Tg mice. Fenofibrate decreased TG and increased HDL size in
      hAI-CIII-AIV-Tg mice as well, but surprisingly, did not elevate serum levels of
      hapoAI or hepatic AI mRNA, suggesting that additional sequences not present in
      the hapoAI transgene (11kb) may be partly responsible for the dampened effect on
      HDL-C seen in hAI-CIII-AIV-Tg mice. Since hAI-CIII-AIV-Tg mouse mimics
      fenofibrate effects seen in humans, this transgenic mouse could serve as a better
      predictive model for screening HDL-C raising compounds.

PMID- 21081178
TI  - Civil society: a critical new advocate for vaccination in Europe.
AB  - The vaccinology landscape has changed, with national authorities now being
      increasingly accountable to new stakeholders such as health insurers, regional
      regulatory bodies, the media, and civil society. Here, we discuss how civil
      society organisations (CSOs), such as patient and women's groups, have become
      important drivers in the introduction and sustainability of new vaccination
      programs. This shift in public implication in vaccine policy has been well
      illustrated in the recent introduction of human papillomavirus (HPV) vaccination
      in Europe. Patient and women's groups which were traditionally focused on
      advocacy of treatments have also become advocates for prevention with the advent
      of HPV vaccination. Civil society advocacy at the European level supported key
      resolutions and white papers which in turn informed national recommendations on
      cervical cancer vaccination. CSOs were also active at the national level,
      supporting national policy makers. These organisations may bring innovative and
      effective new approaches to communication on vaccination benefits, using public
      events, celebrities and various social media. Working with experts, CSOs can also
      be an important bridge from the science to the lay public. This may provide a
      vital counterbalance to media hype and antivaccination groups, although CSOs may
      also be active and vocal opponents of immunization. The successful implementation
      and sustainability of future vaccination programs against infections such as HIV
      will be dependent upon the active participation of civil society to inform, to
      reassure and to maintain public trust.

PMID- 21081179
TI  - A letter from the Editors.

PMID- 21081180
TI  - Identification of region-specific genes in the early chicken endoderm.
AB  - In vertebrates, the endoderm gives rise to the epithelial lining of the digestive
      tract, respiratory system and endocrine organs. After gastrulation, the newly
      formed endoderm gradually becomes regionalized and differentiates into specific
      organs. To understand the molecular basis of early endoderm regionalization,
      which is largely unknown, it is necessary to identify novel region-specific genes
      as candidates potentially involved in this process. Applying an Affymetrix Array
      based approach we aimed for the identification of genes specifically upregulated
      in the foregut or mid-/hindgut endoderm at the onset of regionalization. Several
      genes exhibiting spatial and temporal restricted expression patterns in the
      developing early endoderm were identified and their expression was validated via
      RT-PCR and whole mount in situ hybridization. We report here the detailed gene
      expression patterns of two novel genes specifically associated with foregut
      endoderm and of eight novel genes specifically expressed in the mid-/hindgut
      endoderm at HH stages 10-11. Future functional analysis of these genes may help
      to elucidate the mechanisms involved in endoderm development and regionalization.

PMID- 21081181
TI  - New isoforms of human mitochondrial transcription factor A detected in normal and
      tumoral cells.
AB  - Novel alternatively spliced variants of the human mitochondrial transcription
      factor A predicted by the computational tool ASPic were experimentally validated
      in different normal and tumoral human tissues by RT-PCR and DNA sequencing. The
      comparison between the 5'UTR length and the distribution of the different
      transcripts showed that the transcripts with the shortest 5'UTR are present in
      all the investigated tissues, while the longest 5'UTR seems to be related to
      tissue-specificity. Studies about the localization and function of the most
      widely diffuse alternative isoform Tr6 were carried out.

PMID- 21081182
TI  - Proteomic changes in the gills of wild-type and transgenic radiosensitive medaka
      following exposure to direct irradiation and to X-ray induced bystander signals.
AB  - The directly irradiated and bystander gill proteome was examined in wild-type and
      radiosensitive transgenic medaka. Direct irradiation increased the expression of
      annexin max 3, creatine kinase (CK), and lactate dehydrogenase (LDH) in both
      strains and reduced annexin A4 in wild-type medaka only. In bystander fish, same
      strain pairings increased CK and LDH in both strains and increased annexin max 3
      and annexin A4 in radiosensitive medaka. Mixed strain pairings revealed that, in
      bystander fish, annexin max 3 was only increased by a bystander signal
      originating from a radiosensitive source, annexin A4 was increased in
      radiosensitive bystanders irrespective of the signal source, and CK and LDH were
      increased if either the bystander signal origin or the recipient bystander fish
      was radiosensitive. Warm-temperature acclimation related 65-kDa protein (Wap65)
      was increased in all bystander medaka, whether they were paired with the same or
      opposite strain and chromosome 5 SR-like CTD-associated factor (SR=serine
      argenine-rich, CTD=C-terminal domain) (SCAF) protein was increased in
      radiosensitive bystander medaka only. Annexin A4, CK and LDH are associated with
      apoptosis and mirror the increase in apoptotic bodies previously reported in
      irradiated and bystander medaka, whereas increased Wap65 and LDH suggest a
      protective response. Thus the proteomic changes reported here could indicate both
      immediate protection and longer term adaptation to subsequent radiation exposure.
      In addition this investigation provides further evidence to show that the
      bystander signal can override the intrinsic genetically determined response and
      also that signal production and response can be modulated independently.

PMID- 21081183
TI  - Effects of gentamicin and gentamicin-RGD coatings on bone ingrowth and
      biocompatibility of cementless joint prostheses: an experimental study in
      rabbits.
AB  - Antimicrobial coatings are of interest as a means to improve infection
      prophylaxis in cementless joint arthroplasty. However, those coatings must not
      interfere with the essential bony integration of the implants. Gentamicin
      hydroxyapatite (gentamicin-HA) and gentamicin-RGD (arginine-glycine-aspartate)-HA
      coatings have recently been shown to significantly reduce infection rates in a
      rabbit infection prophylaxis model. The purpose of the current study was to
      investigate the in vitro elution kinetics and in vivo effects of gentamicin-HA
      and gentamicin-RGD-HA coatings on new bone formation, implant integration and
      biocompatibility in a rabbit model. In vitro elution testing showed that 95% and
      99% of the gentamicin was released after 12 and 24 h, respectively. The in vivo
      study comprised 45 rabbits in total, with six animals for each of the gentamicin
      HA, gentamicin-RGD-HA group and control pure HA coating groups for the 4 week
      time period, and nine animals for each of the three groups for the 12 week
      observation period. A 2.0 mm steel K-wire with one of the coatings under test was
      placed in the intramedullary canal of the tibia. After 4 and 12 weeks the tibiae
      were harvested and three different areas (proximal metaphysis, shaft area, distal
      metaphysis) were assessed by quantitative and qualitative histology for new bone
      formation, direct implant-bone contact and the formation of multinucleated giant
      cells. The results exhibited high standard deviations in all subgroups. There was
      a trend towards better bone formation and better direct implant contact in the
      pure HA coating group compared with both gentamicin coatings after 4 and 12
      weeks, which was, however, not statistically significant. The number of
      multinucleated giant cells did not differ significantly between the three groups
      at both time points. In summary, both gentamicin coatings with 99% release of
      gentamicin within 24 h revealed good biocompatibility and bony integration, which
      was not statistically significant different compared with pure HA coating.
      Limitations of the study are the high standard deviation of the results and the
      limited number of animals per time point.

PMID- 21081184
TI  - Evaluation of viscoelastic poly(ethylene glycol) sols as vitreous substitutes in
      an experimental vitrectomy model in rabbits.
AB  - The aim of this study was to employ an experimental protocol for in vivo
      evaluation of sols of 5 wt.% poly(ethylene glycol) (PEG) in phosphate-buffered
      saline as artificial vitreous substitutes. A 20 gauge pars plana vitrectomy and
      posterior vitreous detachment were performed in the right eye of eight pigmented
      rabbits. Approximately 1 ml of the viscoelastic PEG sols was then injected into
      the vitreous space of six eyes. PEG with an average molecular weight of 300,000
      and 400,000 g mol(-1) was used in two and four eyes, respectively. Two eyes
      received balanced salt solution and served as controls. Full-field
      electroretinography was carried out and intra-ocular pressure (IOP, palpation)
      measured pre- and post-operatively at regular intervals up to 41 days. The
      rabbits were killed and the eyes examined by retinal photography, gross
      macroscopic examination and histology. The viscoelastic sols were successfully
      injected and remained translucent throughout the post-operative period, with some
      inferior formation of precipitates. None of the eyes displayed IOP elevation post
      operatively, but in three of the PEG sol injected eyes transient hypotony was
      noted. One eye sustained retinal detachment during surgery and another two in the
      post-operative period. ERG recordings confirmed preservation of retinal function
      in three out of four eyes injected with 400,000 g mol(-1) PEG. Histological
      examination revealed up-regulation of glial acidic fibrillary protein in Muller
      cells in PEG sol injected eyes, but normal overall morphology in eyes with
      attached retinas. The viscosity of the sol was not retained throughout the post
      operative period, indicating the demand for polymer cross-linking to increase
      residence time. The results provide promising preliminary results on the use of
      PEG hydrogels as a vitreous substitute.

PMID- 21081185
TI  - Size and nature of emboli produced during carotid artery angioplasty and
      stenting: in vivo study.
AB  - AIM: Microembolization continues to be a major risk for patients undergoing
      carotid artery stenting (CAS) of high-grade atherosclerotic carotid stenoses.
      Further insight into the characteristics and significance of these embolized
      particles was deemed necessary. We aimed to assess the size and composition of
      debris captured by filters during CAS and to determine if this could be predicted
      using standard imaging techniques. METHODS: 20 patients (10 symptomatic, 15 men,
      mean age 64.6 years) undergoing CAS for high-grade ICA stenosis were recruited.
      All underwent pre-operative CT angiography and calcium scoring. All underwent CAS
      using the same protocol. A filter-type embolic protection device (EPD) was used
      and retrieved post-operatively and captured particles underwent analysis using a
      Scanning Electron Microscope (SEM) for counting, sizing, and composition.
      RESULTS: Clinical. Debris was found on 100% of filters when analysed with SEM.
      There were non-significant trends for CAS in asymptomatic patients to produce a
      greater number of smaller, calcified particles while in symptomatic patients we
      observed larger, lipid-rich particles. When stratified according to pre-operative
      calcium scores, 'calcium-rich' plaques produced significantly greater numbers of
      emboli captured on the EPD (p = 0.02). CONCLUSIONS: Filter-type EPDs collect
      debris of significant quantity and size during the CAS procedure as performed in
      our institution. The collected material was likely dislocated from the
      atherosclerotic plaque. CT calcium scoring allows us to predict the nature of
      material captured by the EPD. These data may allow the clinician to individualise
      care during CAS and thus reduce peri-operative risk.

PMID- 21081186
TI  - The interactome of a PTB domain-containing adapter protein, Odin, revealed by
      SILAC.
AB  - Signal transduction pathways are tightly controlled by positive and negative
      regulators. We have previously identified Odin (also known as ankyrin repeat and
      sterile alpha motif domain-containing 1A; gene symbol ANKS1A) as a negative
      regulator of growth factor signaling; however, the mechanisms through which Odin
      regulates these pathways remain to be elucidated. To determine how Odin
      negatively regulates growth factor signaling, we undertook a proteomic approach
      to systematically identify proteins that interact with Odin using the SILAC
      strategy. In this study, we identified 18 molecules that were specifically
      associated in a protein complex with Odin. Our study established that the
      complete family of 14-3-3 proteins occur in a protein complex with Odin, which is
      also supported by earlier reports that identified a few members of the 14-3-3
      family as Odin interactors. Among the novel protein interactors of Odin were CD2
      associated protein, SH3 domain kinase binding protein 1 and DAB2 interacting
      protein. We confirmed 8 of the eighteen interactions identified in the Odin
      protein complex by co-immunoprecipitation experiments. Finally, a literature
      based network analysis revealed that Odin interacting partners are involved in
      various cellular processes, some of which are key molecules in regulating
      receptor endocytosis.

PMID- 21081188
TI  - Damage initiation sites in osteoporotic and normal human cancellous bone.
AB  - Using a finite element (FE) method called biomechanical stereology, Wang et al.
      previously reported increased microcrack formation and propagation in bone
      samples from patients with a history of osteoporotic fracture as compared to
      normal subjects. In this study, we re-analyzed the data from Wang's report to
      determine the microscopic differences between bone tissue from osteoporotic
      patients and normal subjects that caused these different patterns of bone tissue
      damage between the groups. The morphological features examined were the number of
      "voids" (or osteocyte lacunae) visible and the distance of the lacunae from the
      initiation of the microcracks. We found that bone samples from patients with a
      history of osteoporotic fracture contained significantly more lacunae than normal
      control specimens. We also found a significant correlation (r2 = 0.483, p =
      0.001) between the number of lacunae visible in the image and the number of
      microcracks formed. These results help to explain the differences in total
      microcrack number between the osteoporotic and normal subjects reported in our
      previous work.

PMID- 21081189
TI  - FOXP3 and RORgammat: transcriptional regulation of Treg and Th17.
AB  - FOXP3(+)CD4(+)CD25(+) Regulatory T (Treg) cells and IL-17 producing helper T
      cells (Th17) are critical subsets of T cells which play essential roles in immune
      homeostasis. The Forkhead family transcription factor FOXP3 is predominantly
      expressed in Treg cells, where the FOXP3 ensemble is essential for Treg cell
      development and function. As FOXP3 is to Treg cells, the orphan retinoic acid
      nuclear receptor (ROR) family transcription factor RORgammat is essential for
      Th17 development and function. In this review, we summarize recent progress of
      our understanding towards the molecular mechanisms underlying the differentiation
      and function of FOXP3(+) Treg cells and RORgammat expressing Th17 cells. These
      may provide new insights into therapeutic intervention and targeting of human
      immune-deficient diseases.

PMID- 21081190
TI  - Osteoclasts in arthritis and Th17 cell development.
AB  - Bone destruction associated with rheumatoid arthritis (RA) is mainly attributed
      to the abnormal activation of osteoclasts, which are terminally differentiated
      cells of monocyte/macrophage lineage that resorb bone matrix. Studies on the
      immune regulation of osteoclasts in RA have promoted the new research field of
      "osteoimmunology", which investigates the interplay of the skeletal and immune
      systems at the molecular level. This interdisciplinary field is proving to be
      crucial to advances in the treatment of diseases associated with the bone and/or
      immune systems. As for the mechanisms of the bone destruction found in RA,
      accumulating evidence lends support to the theory that interleukin (IL)-17
      producing helper T (Th17) cells induce the expression of receptor activator of
      nuclear factor-kappaB ligand (RANKL) in synovial cells, which in turn stimulates
      the differentiation and activation of osteoclasts together with inflammatory
      cytokines. Thus, inhibition of Th17 is potentially beneficial for the
      amelioration of the bone damage which occurs in RA. A recent study revealed that
      IkappaBzeta is essential to the development of Th17 cells. These findings
      comprise an important advance in our understanding of the pathogenesis of RA and
      potentially effective therapeutic strategies.

PMID- 21081191
TI  - Pharmacology of receptor operated calcium entry in human neutrophils.
AB  - In neutrophils, increases in intracellular calcium [Ca(2+)](i) provide a crucial
      link between inflammatory mediators and inflammatory responses. The modulation of
      [Ca(2+)](i) fluxes in non-excitable cells such as neutrophils has been studied
      for more than 25 years yet remains to be resolved. In these cells, the Ca(2+)
      influx can occur through at least two mechanisms, as follows: one dependent on
      the state of filling of the endoplasmic reticulum Ca(2+) stores, termed store
      operated calcium entry (SOCE), and the other less studied mechanism in
      neutrophils which is not dependent on the state of the Ca(2+) stores but is
      regulated by receptor occupation, termed receptor operated calcium entry (ROCE).
      Over the past ten years, the molecular components of SOCE have been extensively
      characterized, but in neutrophils, the molecular components of ROCE have only
      recently been explored. In this review, we discuss recent research findings that
      have demonstrated an important role for ROCE in human neutrophils. In addition,
      an overview of pharmacological approaches used to discriminate between ROCE and
      SOCE will be discussed. The elucidation of the molecular components of ROCE may
      well provide important pharmacological targets for the development of novel anti
      inflammatory drugs.

PMID- 21081187
TI  - Pol II waiting in the starting gates: Regulating the transition from
      transcription initiation into productive elongation.
AB  - Proper regulation of gene expression is essential for the differentiation,
      development and survival of all cells and organisms. Recent work demonstrates
      that transcription of many genes, including key developmental and stimulus
      responsive genes, is regulated after the initiation step, by pausing of RNA
      polymerase II during elongation through the promoter-proximal region. Thus, there
      is great interest in better understanding the events that follow transcription
      initiation and the ways in which the efficiency of early elongation can be
      modulated to impact expression of these highly regulated genes. Here we describe
      our current understanding of the steps involved in the transition from an
      unstable initially transcribing complex into a highly stable and processive
      elongation complex. We also discuss the interplay between factors that affect
      early transcript elongation and the potential physiological consequences for
      genes that are regulated through transcriptional pausing.

PMID- 21081192
TI  - Retrievable vena cava filters are indicated in high-risk trauma patients.

PMID- 21081193
TI  - Anticoagulation is the most appropriate method of prophylaxis against venous
      thromboembolic disease in high-risk trauma patients.

PMID- 21081194
TI  - Catheter-directed thrombolysis is the appropriate treatment for iliofemoral deep
      venous thrombosis.

PMID- 21081195
TI  - Conventional anticoagulant therapy remains the current standard of care for the
      treatment of iliofemoral deep venous thrombosis.

PMID- 21081196
TI  - Correcting venous insufficiency improves healing of venous ulcers.

PMID- 21081197
TI  - The rationale for the treatment of perforating veins in advanced chronic venous
      insufficiency.

PMID- 21081198
TI  - The rationale for ablation of incompetent perforating veins is not substantiated
      by current clinical evidence.

PMID- 21081199
TI  - Pharmacology of 5-HT6 receptors--Part 1. Preface.

PMID- 21081200
TI  - 5-HT6 medicinal chemistry.

PMID- 21081201
TI  - Patents.

PMID- 21081202
TI  - 5-HT6 receptor characterization.

PMID- 21081203
TI  - 5-HT6 receptor signal transduction second messenger systems.

PMID- 21081204
TI  - Electrophysiology of 5-HT6 receptors.

PMID- 21081205
TI  - Genetic variations and association.

PMID- 21081206
TI  - Pharmacokinetics of 5-HT6 receptor ligands.

PMID- 21081207
TI  - Introduction: HESI workshop on evaluating biological variation in non-transgenic
      crops.

PMID- 21081208
TI  - Emergency ultrasound of the scrotum: a review of the commonest pathologic
      conditions.
AB  - Ultrasound is the first imaging modality to be performed in emergency conditions
      of the scrotum. The commonest pathologic entities are divided into the 4
      following groups: torsion, trauma, infection, and tumors. Sonographic examination
      should be performed as soon as possible to ensure fast diagnosis and treatment.
      Less acute conditions can also be noted while scanning on an emergency basis,
      such as anatomic variants, hydrocele, oscheocele, clinically evident varicocele,
      calcifications, etc. Although not threatening for scrotal integrity, they should
      be assessed during an emergency examination or later on. In this article, complex
      scrotal anatomy is reviewed and the basic examination technique is described. The
      commonest emergency conditions are analyzed, along with their pathophysiological
      basis. Nonemergent entities are also briefly mentioned. Ultrasound images of the
      commonest emergency conditions are demonstrated.

PMID- 21081209
TI  - Complications of esophageal surgery: role of imaging in diagnosis and treatments.
AB  - Esophageal surgery is a common and integral component in the management of hiatal
      hernias, esophageal carcinoma, and esophageal perforation. Understanding the
      expected postsurgical imaging features of these common esophageal surgeries and
      postoperative complications is essential. Image-guided intervention can be used
      to aid the surgeon in the management of many post esophageal surgical
      complications. We discuss the imaging features of the postoperative esophagus and
      the use of imaging, including fluoroscopy and computed tomography, in the
      diagnosis of post esophageal surgical complications and treatment.

PMID- 21081210
TI  - Stress fractures in the young athlete: a pictorial review.
AB  - Stress fractures are an uncommon but important source of pain and disability in
      young athletes. The presentation and differential diagnosis of stress fractures
      in young athletes differs from that of older athletes. This pictorial review
      outlines the pathogenesis and imaging features of stress fractures. Other
      pathologies that can mimic stress fractures and the advantages of the use of
      magnetic resonance imaging will be discussed. An imaging algorithm for a
      suspected stress fracture is suggested.

PMID- 21081211
TI  - Introduction to the Methods issue on in situ hybridization.

PMID- 21081212
TI  - Cardiovascular pharmacology - endothelial control.

PMID- 21081215
TI  - Prostaglandins in action indispensable roles of cyclooxygenase-1 and -2 in
      endothelium-dependent contractions.
AB  - Endothelium regulates local vascular tone by means of releasing relaxing and
      contracting factors, of which the latter have been found to be elevated in
      vascular pathogenesis of hypertension, diabetes, hypercholesterolemia, and aging.
      Endothelium-derived contracting factors (EDCFs) are mainly metabolites of
      arachidonic acid generated by cyclooxygenase (COX), as vasodilatations in
      patients with hypertension, metabolic diseases, or advancing age are improved by
      acute treatment with COX inhibitor indomethacin. COX is presented in two
      isoforms, COX-1 and COX-2, with the former regarded as constitutive and the
      latter mainly expressed upon induction. Experiments with animal models of
      vascular dysfunctions, however, reveal that both isoforms have similar capacity
      to participate in endothelium-dependent contractions, with augmented expression
      and activity. COX-derived prostaglandin (PG) H(2), PGF(2alpha), PGE(2),
      prostacyclin (PGI(2)), and thromboxane A(2) (TxA(2)) are the proposed EDCFs that
      mediate endothelium-dependent contractions via the activation of thromboxane
      prostanoid (TP) receptor in various vascular beds from different species.
      Although COX inhibition seems to be a possible strategy in combating COX
      associated vascular complications, the incidence of adverse cardiovascular
      effects of Vioxx has greatly antagonized this concept. Further review of COX
      inhibitors is required, especially toward the selectivity of coxibs and whether
      it directly inhibits prostacyclin synthase activity. Meanwhile, TP receptor
      antagonism may emerge as a therapeutic alternative to reverse prostanoid-mediated
      vascular dysregulations.

PMID- 21081213
TI  - The cardiovascular physiology and pharmacology of endothelin-1.
AB  - One year after the discovery in 1980 that the endothelium was obligatory for
      acetylcholine to relax isolated arteries, it was clearly shown that the
      endothelium could also promote contraction. In 1988, Dr Yanagisawa's group
      identified endothelin-1 (ET-1) as the first endothelium-derived contracting
      factor. The circulating levels of this short (21 amino acids) peptide were
      quickly determined in humans and it was reported that in most cardiovascular
      diseases, circulating levels of ET-1 were increased and ET-1 was then recognized
      as a likely mediator of pathological vasoconstriction in human. The discovery of
      two receptor subtypes in 1990, ET(A) and ET(B), permitted optimization of
      bosentan, which entered clinical development in 1993, and was offered to patients
      with pulmonary arterial hypertension in 2001. In this report, we discuss the
      physiological and pathophysiological role of endothelium-derived ET-1, the
      pharmacology of its two receptors, focusing on the regulation of the vascular
      tone and as much as possible in humans. The coronary bed will be used as a
      running example, but references to the pulmonary, cerebral, and renal circulation
      will also be made. Many of the cardiovascular complications associated with aging
      and cardiovascular risk factors are initially attributable, at least in part, to
      endothelial dysfunction, particularly dysregulation of the vascular function
      associated with an imbalance in the close interdependence of NO and ET-1, in
      which the implication of the ET(B) receptor may be central.

PMID- 21081214
TI  - Vascular pharmacology of epoxyeicosatrienoic acids.
AB  - Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic
      acid that are produced by the vascular endothelium in responses to various
      stimuli such as the agonists acetylcholine (ACH) or bradykinin or by shear stress
      which activates phospholipase A(2) to release arachidonic acid. EETs are
      important regulators of vascular tone and homeostasis. In the modulation of
      vascular tone, EETs function as endothelium-derived hyperpolarizing factors
      (EDHFs). In models of vascular inflammation, EETs attenuate inflammatory
      signaling pathways in both the endothelium and vascular smooth muscle. Likewise,
      EETs regulate blood vessel formation or angiogenesis by mechanisms that are still
      not completely understood. Soluble epoxide hydrolase (sEH) converts EETs to
      dihydroxyeicosatrienoic acids (DHETs) and this metabolism limits many of the
      biological actions of EETs. The recent development of inhibitors of sEH provides
      an emerging target for pharmacological manipulation of EETs. Additionally, EETs
      may initiate their biological effects by interacting with a cell surface protein
      that is a G protein-coupled receptor (GPCR). Since GPCRs represent a common
      target of most drugs, further characterization of the EET receptor and synthesis
      of specific EET agonists and antagonist can be used to exploit many of the
      beneficial effects of EETs in vascular diseases, such as hypertension and
      atherosclerosis. This review will focus on the current understanding of the
      contribution of EETs to the regulation of vascular tone, inflammation, and
      angiogenesis. Furthermore, the therapeutic potential of targeting the EET pathway
      in vascular disease will be highlighted.

PMID- 21081216
TI  - TP receptors and oxidative stress hand in hand from endothelial dysfunction to
      atherosclerosis.
AB  - Thromboxane A(2) and the activation of TP receptors that it causes play an
      important role in platelet aggregation and therefore in thrombosis. However, TP
      receptors are also involved in the pathologies of the vascular wall including
      impaired endothelium-dependent vasodilation, increased oxidant generation, and
      increased expression of adhesion molecules. The beneficial effects of TP
      antagonists on the vascular wall attenuate these features of vascular disease.
      They are not shared by aspirin. In fact, TP antagonists are active in patients
      treated with aspirin, indicating that their potential beneficial effects are
      mediated by mechanisms different from the antithrombotic actions of aspirin. Our
      studies have demonstrated the vascular benefits of TP antagonists in experimental
      animals, particularly in models of diabetes mellitus, in which elevated levels of
      eicosanoids play a role not only in vascular pathologies but also in those of the
      kidney and other tissues. They suggest that TP blockade protects against
      fundamental and widespread tissular dysfunction associated with metabolic disease
      including hyperlipidemia and hyperglycemia. TP receptor antagonists represent a
      promising avenue for the prevention of vascular disease in part because of these
      pleiotropic actions that extend beyond their antithrombotic properties.

PMID- 21081217
TI  - Regulation of endothelial cell tetrahydrobiopterin pathophysiological and
      therapeutic implications.
AB  - Tetrahydrobiopterin (BH(4)) is a critical cofactor for the nitric oxide
      synthases. In the absence of BH(4), these enzymes become uncoupled, fail to
      produce nitric oxide, and begin to produce superoxide and other reactive oxygen
      species (ROS). BH(4) levels are modulated by a complex biosynthetic pathway,
      salvage enzymes, and by oxidative degradation. The enzyme GTP cyclohydrolase-1
      catalyzes the first step in the de novo synthesis of BH(4) and new evidence shows
      that this enzyme is regulated by phosphorylation, which reduces its interaction
      with its feedback regulatory protein (GFRP). In the setting of a variety of
      common diseases, such as atherosclerosis, hypertension, and diabetes, reactive
      oxygen species promote oxidation of BH(4) and inhibit expression of the salvage
      enzyme dihydrofolate reductase (DHFR), promoting accumulation of BH(2) and NOS
      uncoupling. There is substantial interest in therapeutic approaches to increasing
      tissue levels of BH(4), largely by oral administration of this agent. BH(4)
      treatment has proved effective in decreasing atherosclerosis, reducing blood
      pressure, and preventing complications of diabetes in experimental animals. While
      these basic studies have been very promising, there are only a few studies
      showing any effect of BH(4) therapy in humans in treatment of these common
      problems. Whether BH(4) or related agents will be useful in treatment of human
      diseases needs additional study.

PMID- 21081218
TI  - Polyphenol-induced endothelium-dependent relaxations role of NO and EDHF.
AB  - The Mediterranean diet has been associated with greater longevity and quality of
      life in epidemiological studies. Indeed, because of the abundance of fruits and
      vegetables and a moderate consumption of wine, the Mediterranean diet provides
      high amounts of polyphenols thought to be essential bioactive compounds that
      might provide health benefits in terms of cardiovascular diseases and mortality.
      Several polyphenol-rich sources, such as grape-derived products, cocoa, and tea,
      have been shown to decrease mean blood pressure in patients with hypertension.
      The improvement of the endothelial function is likely to be one of the mechanisms
      by which polyphenols may confer cardiovascular protection. Indeed, polyphenols
      are able to induce nitric oxide (NO)-mediated endothelium-dependent relaxations
      in a large number of arteries including the coronary artery; they can also induce
      endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations in some of
      these arteries. Altogether, these mechanisms might contribute to explain the
      antihypertensive and cardio-protective effects of polyphenols in vivo. The aim of
      this review was to provide a nonexhaustive analysis of the effect of several
      polyphenol-rich sources and isolated compounds on the endothelium in in vitro, ex
      vivo, and in vivo models as well as in humans.

PMID- 21081219
TI  - Organic nitrates and nitrate tolerance--state of the art and future developments.
AB  - The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon
      chronic administration due to the rapid development of nitrate tolerance. The
      mechanism of this phenomenon has puzzled several generations of scientists, but
      recent findings have led to novel hypotheses. The formation of reactive oxygen
      and nitrogen species in the mitochondria and the subsequent inhibition of the
      nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear
      to play a central role, at least for GTN, that is, bioactivated by ALDH-2.
      Importantly, these findings provide the opportunity to reconcile the two
      "traditional" hypotheses of nitrate tolerance, that is, the one postulating a
      decreased bioactivation and the concurrent one suggesting a role of oxidative
      stress. Furthermore, recent animal and human experimental studies suggest that
      the organic nitrates are not a homogeneous group but demonstrate a broad
      diversity with regard to induction of vascular dysfunction, oxidative stress, and
      other side effects. In the past, attempts to avoid nitrate-induced side effects
      have focused on administration schedules that would allow a "nitrate-free
      interval"; in the future, the role of co-therapies with antioxidant compounds and
      of activation of endogeneous protective pathways such as the heme oxygenase 1 (HO
      1) will need to be explored. However, the development of new nitrates, for
      example, tolerance-free aminoalkyl nitrates or combination of nitrate groups with
      established cardiovascular drugs like ACE inhibitors or AT(1)-receptor blockers
      (hybrid molecules) may be of great clinical interest.

PMID- 21081220
TI  - Vascular actions of adipokines molecular mechanisms and therapeutic implications.
AB  - Adipose tissue is a critical regulator of vascular function, which until recently
      had been virtually ignored. Almost all blood vessels are surrounded by
      perivascular adipose tissue, which is actively involved in the maintenance of
      vascular homeostasis by producing "vasocrine" signals such as adipokines.
      Adiponectin and adipocyte fatty acid binding protein (A-FABP), both of which are
      major adipokines predominantly produced in adipose tissue, have recently been
      shown to be pivotal modulators of vascular function. Adiponectin has multiple
      beneficial effects on cardiovascular health. It prevents obesity-induced
      endothelial dysfunction by inducing nitric oxide production, suppressing
      endothelial cell activation, inhibiting reactive oxygen species and apoptosis,
      and promoting endothelial cell repair. By contrast, A-FABP plays a detrimental
      role in vascular dysfunction and atherosclerosis, mainly by acting as a lipid
      sensor to transmit toxic lipids-induced vascular inflammation through induction
      of endoplasmic reticulum stress. Decreased production of adiponectin and/or
      elevated expression of A-FABP are important contributors to the pathogenesis of
      obesity-induced endothelial dysfunction and cardiovascular disease. This chapter
      highlights recent advances in both clinical investigations and animal studies
      promoting the understanding of the roles of adiponectin and A-FABP in the
      modulation of vascular function, and discusses the possibilities of using these
      two adipokines as therapeutic targets to design new drugs for preventing vascular
      disease associated with obesity and diabetes.

PMID- 21081222
TI  - Coacervation of tropoelastin.
AB  - The coacervation of tropoelastin represents the first major stage of elastic
      fiber assembly. The process has been modeled in vitro by numerous studies,
      initially with mixtures of solubilized elastin, and subsequently with synthetic
      elastin peptides that represent hydrophobic repeat units, isolated hydrophobic
      domains, segments of alternating hydrophobic and cross-linking domains, or the
      full-length monomer. Tropoelastin coacervation in vitro is characterized by two
      stages: an initial phase separation, which involves a reversible inverse
      temperature transition of monomer to n-mer; and maturation, which is defined by
      the irreversible coalescence of coacervates into large species with fibrillar
      structures. Coacervation is an intrinsic ability of tropoelastin. It is primarily
      influenced by the number, sequence, and contextual arrangement of hydrophobic
      domains, although hydrophilic sequences can also affect the behavior of the
      hydrophobic domains and thus affect coacervation. External conditions including
      ionic strength, pH, and temperature also directly influence the propensity of
      tropoelastin to self-associate. Coacervation is an endothermic, entropically
      driven process driven by the cooperative interactions of hydrophobic domains
      following destabilization of the clathrate-like water shielding these regions.
      The formation of such assemblies is believed to follow a helical nucleation model
      of polymerization. Coacervation is closely associated with conformational
      transitions of the monomer, such as increased beta-structures in hydrophobic
      domains and alpha-helices in cross-linking domains. Tropoelastin coacervation in
      vivo is thought to mainly involve the central hydrophobic domains. In addition,
      cell-surface glycosaminoglycans and microfibrillar proteins may regulate the
      process. Coacervation is essential for progression to downstream elastogenic
      stages, and impairment of the process can result in elastin haploinsufficiency
      disorders such as supravalvular aortic stenosis.

PMID- 21081223
TI  - Complex coacervates as a foundation for synthetic underwater adhesives.
AB  - Complex coacervation was proposed to play a role in the formation of the
      underwater bioadhesive of the Sandcastle worm (Phragmatopoma californica) based
      on the polyacidic and polybasic nature of the glue proteins and the balance of
      opposite charges at physiological pH. Morphological studies of the secretory
      system suggested that the natural process does not involve complex coacervation
      as commonly defined. The distinction may not be important because electrostatic
      interactions likely play an important role in the formation of the sandcastle
      glue. Complex coacervation has also been invoked in the formation of adhesive
      underwater silk fibers of caddisfly larvae and the adhesive plaques of mussels. A
      process similar to complex coacervation, that is, condensation and dehydration of
      biopolyelectrolytes through electrostatic associations, seems plausible for the
      caddisfly silk. This much is clear, the sandcastle glue complex coacervation
      model provided a valuable blueprint for the synthesis of a biomimetic, water
      borne, underwater adhesive with demonstrated potential for repair of wet tissue.

PMID- 21081221
TI  - Cardiovascular effects of erythropoietin an update.
AB  - Erythropoietin (EPO) is a therapeutic product of recombinant DNA technology and
      it has been in clinical use as stimulator of erythropoiesis over the last two
      decades. Identification of EPO and its receptor (EPOR) in the cardiovascular
      system expanded understanding of physiological and pathophysiological role of
      EPO. In experimental models of cardiovascular and cerebrovascular disorders, EPO
      exerts protection either by preventing apoptosis of cardiac myocytes, smooth
      muscle cells, and endothelial cells, or by increasing endothelial production of
      nitric oxide. In addition, EPO stimulates mobilization of progenitor cells from
      bone marrow thereby accelerating repair of injured endothelium and
      neovascularization. A novel signal transduction pathway involving EPOR--beta
      common heteroreceptor is postulated to enhance EPO-mediated tissue protection. A
      better understanding of the role of beta-common receptor signaling as well as
      development of novel analogs of EPO with enhanced nonhematopoietic protective
      effects may expand clinical application of EPO in prevention and treatment of
      cardiovascular and cerebrovascular disorders.

PMID- 21081224
TI  - Altered self-assembly and apatite binding of amelogenin induced by N-terminal
      proline mutation.
AB  - OBJECTIVE: A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to
      result in hypomineralised amelogenesis imperfecta (AI). This study aims to test
      the hypothesis that the given mutation affects the self-assembly of amelogenin
      molecules and impairs their ability to conduct the growth of apatite crystals.
      DESIGN: Recombinant human full-length wild-type (rh174) and p.P70T mutated
      amelogenins were analysed using dynamic light scattering (DLS), protein
      quantification assay and atomic force microscopy (AFM) before and after the
      binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated
      by both amelogenins in a dynamic titration system was observed using AFM.
      RESULTS: As compared to rh174 amelogenin, p.P70T mutant displayed significantly
      increased sizes of the assemblies, higher binding affinity to apatite, and
      decreased crystal height. CONCLUSION: Pro-70 plays an important structural role
      in the biologically relevant amelogenin self-assembly. The disturbed regularity
      of amelogenin nanospheres by this single mutation resulted in an increased
      binding to apatite and inhibited crystal growth.

PMID- 21081225
TI  - A click procedure with heterogeneous copper to tether technetium-99m chelating
      agents and rhenium complexes. Evaluation of the chelating properties and
      biodistribution of the new radiolabelled glucose conjugates.
AB  - An efficient protocol was developed to tether chelating agents and rhenium
      complexes onto a glucoside scaffold with a heterogeneous copper catalyst via
      click chemistry. The supported catalyst avoids the formation of unwanted copper
      complexes during the cyclisation step. The possibility to graft a pre-chelated
      M(CO)(3) core by click chemistry onto a biomolecule was highlighted for the first
      time. (99m)Tc(CO)(3)-glucoconjugates displayed excellent in vitro stability, a
      fast in vivo blood clearance and a low specific organ uptake or long-term
      retention in spleen and stomach.

PMID- 21081226
TI  - Trauma exposure characteristics, past traumatic life events, coping strategies,
      posttraumatic stress disorder, and psychiatric comorbidity among people with
      anaphylactic shock experience.
AB  - OBJECTIVES: This study investigated the interrelationship between trauma exposure
      characteristics, past traumatic life events, coping strategies, posttraumatic
      stress disorder (PTSD) symptoms, and psychiatric comorbidity among people after
      anaphylactic shock experience. METHOD: The design was cross-sectional in that 94
      people with anaphylactic shock experience responded to a postal survey. They
      completed the Posttraumatic Stress Disorder Checklist, the General Health
      Questionnaire 28, and the COPE Scale. They also answered questions on trauma
      exposure characteristics. The control group comprised 83 people without
      anaphylaxis. RESULTS: Twelve percent of people with anaphylactic shock experience
      fulfilled the diagnostic criteria for full PTSD. As a group, people with
      anaphylaxis reported significantly more past traumatic life events and
      psychiatric comorbidity than did the control. Partial least squares analysis
      showed that trauma exposure characteristics influenced postanaphylactic shock
      PTSD symptoms and psychiatric comorbidity, which, in turn, influenced coping
      strategies. CONCLUSIONS: People could develop PTSD and psychiatric comorbidity
      symptoms after their experience of anaphylactic shock. The way they coped with
      anaphylactic shock was affected by the severity of these symptoms. Past traumatic
      life events had a limited role to play in influencing outcomes.

PMID- 21081227
TI  - Stability of alexithymia in the general population: an 11-year follow-up.
AB  - OBJECTIVES: There is an ongoing debate concerning the temporal stability of
      alexithymia. Most previous studies have been conducted on clinical populations of
      psychiatric and somatic patients. However, psychiatric and somatic morbidity have
      been found to confound the findings so that in their presence, alexithymia
      appears to be less stable. Nevertheless, few general population studies have been
      published, and there have been no follow-ups longer than 5 years. METHOD: In a
      population-based sample of middle-aged Finnish men, 755 participants completed
      the Toronto Alexithymia Scale (TAS)-26 at baseline and on 11-year follow-up.
      Absolute or mean stability refers to the extent to which scores change over time,
      and it was measured with group comparisons of paired samples. Relative stability
      refers to the consistency of relative differences in alexithymia levels among the
      study subjects, and it was measured with test-retest correlations. RESULTS:
      Changes in the total scores and the subscales of the TAS-26 were all
      statistically significant but had low effect sizes (0.09-0.20) for the change
      suggested absolute stability. The correlations between baseline and follow-up
      scores were high (rho = 0.51-0.63), indicating relative stability. The exclusion
      of depressive symptoms, a history of mental illnesses, and cancer or
      cardiovascular diseases at baseline and at the 4- and 11-year follow-ups did not
      essentially alter these findings. Of the background variables, a higher age
      independently associated with the increase in the TAS-26 scores. Those with
      alexithymia at baseline were more likely to have elevated depressive symptoms at
      the 4- and 11-year follow-ups. CONCLUSIONS: Both the absolute and relative
      stabilities of alexithymia in the general population are high, even for a long
      follow-up period. These results may support the assumption that alexithymia
      represents a stable personality trait in general. Alexithymia may increase
      vulnerability to depressive symptoms.

PMID- 21081228
TI  - Current state and future perspectives of trauma care system in mainland China.
AB  - OBJECTIVE: To investigate the current state of trauma care in mainland China, and
      to propose possible future suggestions for the development of the trauma care
      system in mainland China. METHOD: An extensive Medline/PubMed search on the topic
      of trauma care or trauma care system was conducted. Publications in Chinese that
      could best describe the state of trauma care in China were also included. In
      addition, two meetings were held by Group for Trauma Emergency Care and Multiple
      Injuries, Trauma Society of Chinese Medical Association to discuss the
      development and perspectives of trauma care system in mainland China. Important
      conclusions from the two meetings were included in this publication. RESULTS:
      Trauma has become an increasing public health problem in mainland China in
      association with the rapid growth of the economy over the past 30 years. Although
      great progress has been made in regards to the care of the injured, there is
      still no government agency dedicated to deal with trauma-related issues, or a
      national trauma care system operating on the Chinese mainland. Various trauma
      prevention measures have been taken, but with little effect. Funds contributed to
      trauma-related research has increased in recent years and promoted rapid
      development in this field, but further improvement in research is needed.
      However, many groups such as the Trauma Society of the Chinese Medical
      Association have continued to explore mechanisms for the treatment of trauma
      patients and have developed various types of regional trauma care systems,
      resulting in improved trauma care and a better outcome for the injured.
      CONCLUSIONS: Although great progress has been made in trauma care in mainland
      China, there are many failings. To improve trauma care in China, the
      establishment of a sophisticated trauma system and various enhancements on trauma
      prevention are urgently required.

PMID- 21081229
TI  - Acute exercise improves postprandial cardiovascular risk factors in overweight
      and obese individuals.
AB  - OBJECTIVES: The effects of 30 min of exercise on postprandial lipaemia in the
      overweight and obese are unknown as previous studies have only investigated bouts
      of at least 60 min in lean, healthy individuals. The aim of this study was to
      investigate whether a single 30-min bout of resistance, aerobic or combined
      exercise at moderate-intensity would decrease postprandial lipaemia, glucose and
      insulin levels as well as increase resting energy expenditure and increase fat
      oxidation following a high fat meal consumed 14 h after the exercise bout, in
      overweight and obese individuals compared to no exercise. We also compared the
      effects of the different exercise modalities. METHODS: This study was a
      randomized cross-over design which examined the postprandial effects of 30 min of
      different types of exercise in the evening prior to a breakfast meal in
      overweight and obese men and women. Participants were randomized on four
      occasions, each one-week apart, to each condition; either no exercise, aerobic
      exercise, resistance exercise or a combination of aerobic exercise and resistance
      exercise. RESULTS: An acute bout of combination training did not have any
      significant effect on postprandial measurements compared to no exercise. However,
      aerobic exercise significantly reduced postprandial triglyceride levels by 8%
      compared to no exercise (p=0.02) and resistance exercise decreased postprandial
      insulin levels by 30% compared to aerobic exercise (p=0.01). CONCLUSION: These
      results indicate that a single moderate-intensity 30 min bout of aerobic or
      resistance exercise improves risk factors associated with cardiovascular disease
      in overweight and obese individuals.

PMID- 21081230
TI  - A component tracking algorithm for accelerated and improved liquid chromatography
      mass spectrometry method development.
AB  - A method for tracking of sample components during liquid chromatography-mass
      spectrometry (LC-MS) method development has been proposed. The method manages to,
      fully automatically and without user intervention, find the chromatographic peaks
      in the data sets, discriminate them to sample components and track them when the
      separation conditions have been changed. The algorithm utilises the resolution
      obtained from all considered data sets and has the ability to discriminate the
      non informative parts. The technique has a great sensitivity even in cases where
      a majority of the tracked components cannot easily be spotted by means of
      traditional total ion chromatogram (TIC) or base peak chromatogram (BPC)
      representations. The method was tested on an experimental sample using six
      different columns and an average of 79% of the suggested sample components could
      be successfully tracked at a minimum area of 0.05% of the main component in the
      sample. 66 components with 79-92% of the total suggested component area were able
      to be tracked between all data sets. The method could be used to rapidly
      investigate selectivity during different types of separation conditions.

PMID- 21081231
TI  - Feasibility of gas chromatography-microchip atmospheric pressure photoionization
      mass spectrometry in analysis of anabolic steroids.
AB  - Mass spectrometers equipped with atmospheric pressure ion sources (API-MS) have
      been designed to be interfaced with liquid chromatographs (LC) and have rarely
      been connected to gas chromatographs (GC). Recently, we introduced a heated
      nebulizer microchip and showed its potential to interface liquid microseparation
      techniques and GC with API-MS. This study demonstrates the feasibility of GC
      microchip atmospheric pressure photoionization-tandem mass spectrometry (GC
      MUAPPI-MS/MS) in the analysis of underivatized anabolic steroids in urine. The
      APPI microchip provides high ionization efficiency and produces abundant
      protonated molecules or molecular ions with minimal fragmentation. The
      feasibility of GC-MUAPPI-MS/MS in the analysis of six selected anabolic steroids
      in urine samples was studied with respect to intra-batch repeatability,
      linearity, linear range, and limit of detection (LOD). The method showed good
      sensitivity (LODs 0.2-1 ng/mL), repeatability (relative standard deviation<10%),
      and linearity (regression coefficient>=0.9995) and, therefore, high potential for
      the analysis of anabolic steroids. Quantitative performance of the method was
      tested with two authentic urine samples, and the results were in good agreement
      with those obtained with conventional GC-electron ionization-MS after
      derivatization.

PMID- 21081232
TI  - Effects of the gradient profile, sample volume and solvent on the separation in
      very fast gradients, with special attention to the second-dimension gradient in
      comprehensive two-dimensional liquid chromatography.
AB  - Gradient elution provides significant improvement in peak capacity with respect
      to isocratic conditions and therefore should be used in comprehensive two
      dimensional LC*LC, both in the first and in the second dimension, where, however,
      gradients are limited to a short time period available for separation, usually 1
      min or less. Gradient conditions spanning over a broad mobile phase composition
      range in each second-dimension fraction analysis are used with generic "full in
      fraction" (FIF) gradients. "Segment in fraction" (SIF) gradients cover a limited
      gradient range adjusted independently to suit changing lipophilicity range of
      compounds transferred to the second dimension during the first-dimension gradient
      run and to provide regular coverage of the two-dimensional retention space.
      Optimization of the gradient profiles is important tool for achieving high two
      dimensional peak capacity and savings of the separation time in comprehensive
      LC*LC. Calculations based on the well-established gradient-elution theory can be
      used to predict the elution times and bandwidths in fast gradients, taking into
      account increased probability of pre-gradient or post-gradient elution. The
      fraction volumes transferred into the second dimension may significantly affect
      the second-dimension bandwidths, especially at high elution strength of the
      fraction solvent, which may cause even band distortion or splitting in combined
      normal-phase (HILIC)-RP systems, but also in some two-dimensional RP-RP systems.
      In the present work, the effects of the fast gradient profile, of the sample
      volume and solvent on the elution time and bandwidths were investigated on a
      short column packed with fused-core porous-shell particles, providing narrow
      bandwidths and fast separations at moderate operating pressure.

PMID- 21081233
TI  - Mass transfer mechanism in liquid chromatography columns packed with shell
      particles: would there be an optimum shell structure?
AB  - The mass transfer mechanisms in columns packed with old (55 MUm Zipax and 5 MUm
      Poroshell) and recently commercialized shell particles (2.7 MUm Halo-C(18) and
      Kinetex-C(18)) were investigated from a physico-chemical point of view. Combining
      a model of diffusion in heterogeneous packed beds (effective medium theory) with
      values of the heights equivalent to a theoretical plate (HETPs derived from the
      first and second central moments of the elution profiles) and of the peak
      variances provided by the peak parking method, we demonstrate that columns packed
      with current shell particles perform better than those packed with fully porous
      particles in resolving low molecular weight compounds because the eddy diffusion
      term of the van Deemter equation of the former is markedly smaller. The
      calculation of eddy diffusion in column beds suggests that the smaller A terms
      are due to smaller trans-column velocity bias in columns packed with shell
      particles. We also show that the mass transfer of large molecules (e.g.,
      proteins) is faster when the internal volume accessible to the analyte increases.
      Therefore, it is suggested that shell particles made of concentric layers with
      average pore sizes increasing with increasing diameter would provide columns with
      higher efficiency.

PMID- 21081234
TI  - Au nanoparticles as a novel coating for solid-phase microextraction.
AB  - A novel solid-phase microextraction fiber based on a stainless steel wire coated
      with Au nanoparticles was prepared and has been applied, coupled with gas
      chromatography, to the extraction of aromatic hydrophobic organic chemical
      pollutants in rainwater and soil extract. The solid-phase microextraction fiber
      exhibited excellent extraction efficiency and selectivity. Effects of extraction
      time, extraction temperature, ionic strength, stirring rate and desorption
      conditions were investigated and optimized. Single fiber repeatability and fiber
      to-fiber reproducibility were less than 7.90% and 26.40%, respectively. The
      calibration curves were linear in a wide range for all analytes. Correlation
      coefficients ranged from 0.9941 to 0.9993. The as-established SPME-GC method was
      used successfully to two real natural samples. Recovery of analytes spiked at 10
      MUg L(-1) and 100 MUg L(-1) ranged from 78.4% to 119.9% and the relative standard
      deviations were less than 11.3%.

PMID- 21081235
TI  - Selecting a reduced suite of diagnostic ratios calculated between petroleum
      biomarkers and polycyclic aromatic hydrocarbons to characterize a set of crude
      oils.
AB  - A set of 34 crude oils was analysed by GC-MS (SIM mode) and a suite of 28
      diagnostic ratios (DR) calculated. They involved 18 ratios between biomarker
      molecules (hopanes, steranes, diasteranes and triaromatic steroids) and 10
      quotients between polycyclic aromatic hydrocarbons. Three unsupervised pattern
      recognition techniques (i.e., principal components analysis, heatmap hierarchical
      cluster analysis and Kohonen neural networks) were employed to evaluate the final
      dataset and, thus, ascertain whether the crude oils grouped as a function of
      their geographical origin. In addition, an objective variable selection procedure
      based on Procrustes Rotation was undertaken to select a reduced set of DR that
      comprised for most of the information in the original data without loosing
      relevant information. A reduced set of four DR (namely; TA21, D2/P2, D3/P3 and
      B(a)F/4-Mpy) demonstrated to be sufficient to characterize the crude oils and the
      groups they formed.

PMID- 21081236
TI  - Metal ion mediated molecularly imprinted polymer for selective capturing
      antibiotics containing beta-diketone structure.
AB  - A new molecularly imprinted polymer (MIP) targeting to quinolones (Qs) and
      tetracyclines (TCs) was synthesized using itaconic acid (ITA) and ciprofloxacin
      (CIP) as a functional monomer and template molecule, respectively. Factors
      affecting the overall performance of MIP were investigated, and the results
      showed that Fe(3+) ion play a vital role in the formation of MIP with high
      molecular imprinting effect. Meanwhile, the chelating ability of monomer, species
      of template molecule, as well as the molar ratio of monomer and template also
      contribute to the performance of the obtained MIP. Cyclic voltammetry verified
      that, with the participation of Fe(3+) ions, a ternary complex of ITA-Fe(3+)-CIP
      could be formed before polymerization. Compared with conventional MIP prepared
      from commonly used monomer, methacrylic acid (MAA), the new MIP show
      significantly enhanced molecular imprinting effect and higher capacity for
      specific adsorption of target compounds as revealed by static and dynamic binding
      experiments. The MIP was successfully used as solid-phase extraction (SPE)
      adsorbent for enriching a broad spectrum of antibiotics containing beta-diketone
      structure from surface water sample. HPLC detection showed that high recovery
      rate (78.6-113.6%) was found in these spiked antibiotics, whereas recovery rate
      for the non structurally related drugs, epinephrine (EP) and dopamine (DOPA), was
      very low (4.7-7.6%) on the MIP cartridges. The results demonstrate that the MIP
      prepared by the strategy proposed in this work, could specifically target to a
      series of structurally related antibiotics containing beta-diketone structure.

PMID- 21081237
TI  - Comparative evaluation of software for retention time alignment of gas
      chromatography/time-of-flight mass spectrometry-based metabonomic data.
AB  - In chromatography-based metabonomic research, retention time (RT) alignment of
      chromatographic peaks poses a challenge for the accurate profiling of biomarkers.
      Although a number of RT alignment software has been reported, the performance of
      these software packages have not been comprehensively evaluated. This study aimed
      to evaluate the RT alignment accuracy of publicly available and commercial RT
      alignment software. Two gas chromatography/mass spectrometry (GC/MS) datasets
      acquired from a mixture of standard metabolites and human bladder cancer urine
      samples, were used to assess three publicly available software packages,
      MetAlign, MZmine and TagFinder, and two commercial applications comprising the
      Calibration feature and Statistical Compare of ChromaTOF software. The overall RT
      alignment accuracies in aligning standard compounds mixture were 93, 92, 74, 73
      and 42% for Calibration feature, MZmine, MetAlign, Statistical Compare and
      TagFinder, respectively. Additionally, unique trends were observed for the
      individual software with regards to the different experimental conditions related
      to extent and direction of RT shifts. Conflicting performance was observed for
      human urine samples suggesting that RT misalignments still occurred despite the
      use of RT alignment software. While RT alignment remains an inevitable step in
      data preprocessing, metabonomic researchers are recommended to perform manual
      check on the RT alignment of important biomarkers as part of their validation
      process.

PMID- 21081238
TI  - Selectable one-dimensional or two-dimensional gas chromatography
      olfactometry/mass spectrometry with preparative fraction collection for analysis
      of ultra-trace amounts of odor compounds.
AB  - A novel selectable one-dimensional ((1)D) or two-dimensional ((2)D) gas
      chromatography-olfactometry/mass spectrometry with preparative fraction
      collection (selectable (1)D/(2)D GC-O/MS with PFC) system was developed. The main
      advantages of this system are the simple and fast selection of (1)D GC-O/MS or
      (2)D GC-O/MS or (1)D GC-PFC or (2)D GC-PFC operation with a mouse click (without
      any instrumental set-up change), and total transfer of enriched compounds with
      thermal desorption (TD) on the same system for identification with (2)D GC-O/MS
      analysis. Recovery of PFC enrichment with 20 injection cycles of 15 model
      compounds at 500pg each (e.g. alcohol, aldehyde, ester, lactone, and phenol) was
      very good with recoveries in the range of 98-116%. The feasibility and benefit of
      the proposed system was demonstrated with an identification of off-flavor
      compounds (e.g. 2,4,6-trichloroanisole (TCA), 2-isobutyl-3-methoxypyrazine
      (IBMP), and geosmin) in spiked wine at odor perception threshold level (5-50ngL(
      1)). After parallel stir bar sorptive extraction (SBSE) for 20 aliquots of a
      sample and subsequent PFC enrichment for the odor-active fractions from the 20
      stir bars, three off-flavor compounds were clearly resolved and detected with TD
      (2)D GC-O/MS in scan mode. The good efficiency of SBSE-PFC enrichment in the
      range of 71-78% shows that all analytical steps, e.g. SBSE, TD, (1)D/(2)D GC
      O/MS, and PFC, are quantitative and identification of off-flavor compounds at
      ngL(-1) level in wine is possible.

PMID- 21081239
TI  - Hollow fiber liquid-phase microextraction coupled with gas chromatography-flame
      ionization detection for the profiling of fatty acids in vegetable oils.
AB  - The development of a two phase hollow fiber liquid-phase microextraction
      technique, followed by gas-chromatography-flame ionization detection (GC-FID) for
      the profiling of the fatty acids (FAs) (lauric, myristic, palmitic, stearic,
      palmitoleic, oleic, linoleic, linolenic and arachidic) in vegetable oils is
      described. Heptadecanoic acid methyl ester was used as the internal standard. The
      FAs were transesterified to their corresponding methyl esters prior to the
      extraction. Extraction parameters such as type of extracting solvent,
      temperature, extraction time, stirring speed and salt addition were studied and
      optimized. Recommended conditions were extraction solvent, n-tridecane;
      extraction time, 35 min; extraction temperature, ambient; without addition of
      salt. Enrichment factors varying from 37 to 115 were achieved. Calibration curves
      for the nine FAs were well correlated (r(2)>0.994) within the range of 10-5000
      MUg L(-1). The limit of detection (signal:noise, 3) was 4.73-13.21 ng L(-1). The
      method was successfully applied to the profiling of the FAs in palm oils (crude,
      olein, kernel, and carotino cooking oil) and other vegetable oils (soybean,
      olive, coconut, rice bran and pumpkin). The encouraging enrichments achieved
      offer an interesting option for the profiling of the minor and major FAs in palm
      and other vegetable oils.

PMID- 21081240
TI  - Quantitative determination of 8-isoprostaglandin F(2alpha) in human urine using
      microfluidic chip-based nano-liquid chromatography with on-chip sample enrichment
      and tandem mass spectrometry.
AB  - Urinary 8-isoprostaglandin F(2alpha) (8-isoPGF(2alpha)) has been reported as an
      important biomarker to indicate the oxidative stress status in vivo. In order to
      quantitatively determine the low contents of 8-isoPGF(2alpha) (in sub- to low ng
      mL(-1) range) in physiological fluids, a sensitive detection method has become an
      important issue. In this study, we employed a microfluidic chip-based nano liquid
      chromatography (chip-nanoLC) with on-chip sample enrichment coupled to triple
      quadrupole mass spectrometer (QqQ-MS) for the quantitative determination of 8
      isoPGF(2alpha) in human urine. This chip-nanoLC unit integrates a microfluidic
      switch, a chip column design having a pre-column (enrichment column) for sample
      enrichment prior to an analytical column for separation, as well as a nanospray
      emitter on a single polyimide chip. The introduction of enrichment column offers
      the advantages of online sample pre-concentration and reducing matrix influence
      on MS detection to improve sensitivity. In this study, the chip-nanoLC consisting
      of Zorbax 300A SB-C18 columns and Agilent QqQ Mass spectrometer were used for
      determining 8-isoPGF(2alpha) in human urine. Gradient elution was employed for
      effective LC separation and multiple reaction monitoring (MRM) was utilized for
      the quantitative determination of 8-isoPGF(2alpha) (m/z 353->193). We employed
      liquid-liquid extraction (LLE)/solid-phase extraction (SPE) for extracting
      analyte and reducing matrix effect from urine sample prior to chip-nanoLC/QqQ-MS
      analysis for determining urinary 8-isoPGF(2alpha). Good recoveries were found to
      be in the range of 83.0-85.3%. The linear range was 0.01-2 ng mL(-1) for urinary
      8-isoPGF(2alpha). In addition, the proposed method showed good precision and
      accuracy for 8-isoPGF(2alpha) spiked synthetic urine samples. Intra-day and inter
      day precisions were 1.8-5.0% and 4.3-5.8%, respectively. The method accuracy for
      intra-day and inter-day assays ranged from 99.3 to 99.9% and 99.4 to 99.7%,
      respectively. Due to its rapidity, enhanced sensitivity, and high recovery, this
      chip-nanoLC/QqQ-MS system was successfully utilized to determine the
      physiological biomarkers such as 8-isoPGF(2alpha) in human urine for clinical
      diagnosis.

PMID- 21081241
TI  - Acute dengue virus myositis: a report of seven patients of varying clinical
      severity including two cases with severe fulminant myositis.
AB  - BACKGROUND: Acute dengue myositis is characterized by fever and myalgia (with or
      without muscle weakness). METHOD: The 7 cases of acute dengue myositis were
      retrospectively evaluated in the present study. Dengue myositis was diagnosed on
      the basis of a clinical picture consistent with the infection, elevated creatine
      phosphokinase, normal CSF, positive serum IgM for dengue virus, and the exclusion
      of other causes. RESULTS: The mean age of patients was 19.4 (range 3-40) years.
      Majority (5) of the patients were male. In our series 3 of the cases suffered
      from fulminant myositis. They were characterized by generalized weaknesses which
      included the respiratory muscles. All the 3 patients had markedly elevated
      creatine phosphokinase levels (ranging from 16,590 to 117,200 IU/L). Two patients
      suffering from fulminant myositis required mechanical ventilation. However, they
      succumbed to their illnesses. The third patient showed signs of improvement. One
      case had paraparesis and an elevated creatine phosphokinase level. However, a
      spontaneous complete recovery was observed. The remaining 3 cases had
      quadriparesis with trunk and neck weaknesses, sparing of respiratory muscles,
      creatine phosphokinase levels up to 3000 U/L. However, a complete recovery was
      observed in these patients within 4 weeks. CONCLUSION: To conclude, early
      respiratory involvement, high creatine phosphokinase values, and severe myalgia
      suggest a severe form of dengue myositis.

PMID- 21081242
TI  - Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are
      associated with risk for and mortality from cancer in a German primary care
      cohort.
AB  - There is growing evidence that patients with type 2 diabetes mellitus have
      increased cancer risk. We examined the association between diabetes, cancer, and
      cancer-related mortality and hypothesized that insulin sensitizers lower cancer
      related mortality. Participants in the Diabetes Cardiovascular Risk and
      Evaluation: Targets and Essential Data for Commitment of Treatment study, a
      nationwide cross-sectional and prospective epidemiological study, were recruited
      from German primary care practices. In the cross-sectional study, subjects with
      type 2 diabetes mellitus had a higher prevalence of malignancies (66/1308, 5.1%)
      compared to nondiabetic subjects (185/6211, 3.0%) (odds ratio, 1.64; 95%
      confidence interval, 1.12-2.41) before and after adjustment for age, sex,
      hemoglobin A(1c), smoking status, and body mass index. Patients on metformin had
      a lower prevalence of malignancies, comparable with that among nondiabetic
      patients, whereas those on any other oral combination treatment had a 2-fold
      higher risk for malignancies even after adjusting for possible confounders;
      inclusion of metformin in these regimens decreased the prevalence of
      malignancies. In the prospective analyses, diabetic patients in general and
      diabetic patients treated with insulin (either as monotherapy or in combination
      with other treatments) had a 2- and 4-fold, respectively, higher mortality rate
      than nondiabetic patients, even after adjustment for potential confounders
      (incidence of cancer deaths in patients with type 2 diabetes mellitus [2.6%] vs
      the incidence of cancer deaths in patients without type 2 diabetes mellitus
      [1.2%]). Our results suggest that diabetes and medications for diabetes, with the
      exception of the insulin sensitizer metformin, increase cancer risk and
      mortality.

PMID- 21081243
TI  - Leptin replacement improves postprandial glycemia and insulin sensitivity in
      human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone:
      a pilot study.
AB  - Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized
      by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and
      recombinant methionyl human leptin (metreleptin) administration has beneficial
      effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients.
      This proof-of-concept study aimed at evaluating whether the combination of
      metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone
      alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected
      patients on HAART. Nine HIV-positive men with at least 6 months of HAART
      exposure, clinical evidence of lipoatrophy, and low leptin concentrations (<=4
      ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized
      to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or
      placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo,
      metreleptin reduced fasting serum insulin concentration, increased adiponectin
      concentration, reduced the homeostasis model assessment index of insulin
      resistance, and attenuated postprandial glycemia in response to a mixed meal (all
      P <= .02), but did not affect trunk and peripheral fat mass. HIV control was not
      affected, and no major adverse effects were observed. Metreleptin administration
      in HIV-positive, leptin-deficient patients with lipoatrophy treated with
      pioglitazone improves postprandial glycemia and insulin sensitivity. Results from
      this pilot study should be confirmed in larger clinical trials.

PMID- 21081244
TI  - Comparative study of the uses of poly(4-vinylpyridine) and
      poly(diallyldimethylammonium) chloride for the removal of perchlorate from
      aqueous solution by polyelectrolyte-enhanced ultrafiltration.
AB  - An application of polyelectrolyte-enhanced ultrafiltration utilizes cationic
      polyelectrolytes to electrostatically bind anionic species. The colloid and
      target anion are then concentrated using an ultrafilter, producing a filtrate
      with a lower concentration of the target. This study compared the performances of
      poly(4-vinylpyridine) (P4VP) and poly(diallyldimethylammonium) chloride (PDADMAC)
      for the removal of perchlorate. Potentiometric titration data revealed that the
      ionization properties of P4VP in aqueous solution vary as functions of titrant
      utilized, degree of protonation, and counterion concentration. The greater
      affinity of perchlorate over chloride for the protonated pyridine residues of
      P4VP provided up to 95.8% retention of perchlorate under the solution conditions
      investigated. Through ultrafiltration experiments, the effects solution pH,
      counterion concentration, and polymer concentration were examined for both P4VP
      and PDADMAC. In addition, the effectiveness of P4VP recovery and reuse was also
      assessed.

PMID- 21081245
TI  - Investigation on the gaseous and particulate emissions of a compression ignition
      engine fueled with diesel-dimethyl carbonate blends.
AB  - The effect of dimethyl carbonate (DMC) on the gaseous and particulate emissions
      of a diesel engine was investigated using Euro V diesel fuel blended with
      different proportions of DMC. Combustion analysis shows that, with the blended
      fuel, the ignition delay and the heat release rate in the premixed combustion
      phase increase, while the total combustion duration and the fuel consumed in the
      diffusion combustion phase decrease. Compared with diesel fuel, with an increase
      of DMC in the blended fuel, the brake thermal efficiency is slightly improved but
      the brake specific fuel consumption increases. On the emission side, CO increases
      significantly at low engine load but decreases at high engine load while HC
      decreases slightly. NO(x) reduces slightly but the reduction is not statistically
      significant, while NO(2) increases slightly. Particulate mass and number
      concentrations decrease upon using the blended fuel while the geometric mean
      diameter of the particles shifts towards smaller size. Overall speaking, diesel
      DMC blends lead to significant improvement in particulate emissions while the
      impact on CO, HC and NO(x) emissions is small.

PMID- 21081246
TI  - Effect of N-acetyl cysteine on orthodontic primers cytotoxicity.
AB  - OBJECTIVES: The aims of this study were to evaluate the cytotoxicity of four
      orthodontic primers, including two hydrophilic and two hydrophobic materials, and
      to investigate the role of the reactive oxygen species (ROS) in induced cell
      damage. Moreover, the effects of the anti-oxidant N-acetyl cysteine (NAC) on
      primers toxicity was analyzed. METHODS: Human gingival fibroblasts (HGF) were
      exposed to different concentrations of primers (0-0.25 mg/ml) in the presence or
      absence of NAC, and the cytotoxicity was assessed by the MTT assay, while cell
      death was quantified by flow cytometry after propidium iodide staining. The
      increase in the induced ROS levels was detected by flow cytometry measuring the
      fluorescence of the oxidation-sensitive dye 2',7'-dichlorofluorescein diacetate
      (DCFH-DA). RESULTS: All materials decreased cell viability in a dose-related
      manner after a 24 h exposure period. Cytotoxicity of orthodontic primers based on
      concentrations which caused a 50% decrease in cell viability (TC50) in HGF was
      ranked as follows (median values): Eagle Fluorsure (0.078 mg/ml)>Transbond XT
      (0.081 mg/ml)>Transbond MIP (0.128 mg/ml)>Ortho solo (0.130 mg/ml). Moreover, in
      HGF cells, all materials induced a dose-dependent increase in ROS levels compared
      to untreated cells. Incubation of HGF with NAC significantly reduced ROS
      production and decreased the cell damage and cytotoxicity caused by all materials
      tested (p<0.001). SIGNIFICANCE: Our results suggested that hydrophilic primers
      were less cytotoxic than hydrophobic materials. Moreover, we demonstrated a major
      role of ROS in the induction of cell death since the antioxidant N-acetyl
      cysteine was able to prevent cell damage induced by all materials tested.

PMID- 21081247
TI  - Effect of temporal pulse shaping on the reduction of laser weld defects in a Pd
      Ag-Sn dental alloy.
AB  - OBJECTIVES: To describe the influence of pulse shaping on the behavior of a
      palladium-based dental alloy during laser welding and to show how its choice is
      effective to promote good weld quality. METHODS: Single spots, weld beads and
      welds with 80% overlapping were performed on Pd-Ag-Sn cast plates. A pulsed
      Nd:Yag laser was used with a specific welding procedure using all the
      possibilities for pulse-shaping: (1) the square pulse shape as the default
      setting, (2) a rising edge slope for gradual heating, (3) a falling edge slope to
      slow the cooling and (4) a combination of a rising and falling edges called
      bridge shape. The optimization of the pulse shape is supposed to enhance
      weldability and produce defect-free welds (cracks, pores...) Vickers
      microhardness measurements were made on cross sections of the welds. RESULTS: A
      correlation between laser welding parameters and microstructure evolution was
      found. Hot cracking and internal porosities were systematically detected when
      using rapid cooling. The presence of these types of defects was significantly
      reduced with the slow cooling of the molten pool. The best weld quality was
      obtained with the use of the bridge shape. SIGNIFICANCE: The use of a slow
      cooling ramp is the only way to significantly reduce the presence of typical
      defects within the welds for this Pd-based alloy studied.

PMID- 21081248
TI  - Ingested (oral) ACTH inhibits EAE.
AB  - Ingested type I IFN and SIRS peptide inhibit EAE. We examined whether another
      immunoactive protein, ACTH, would have similar anti-inflammatory effects in EAE
      after oral administration. B6 mice were immunized and gavaged with control saline
      or ACTH starting on the onset of disease. ACTH decreased clinical score and
      decreased inflammatory foci. CNS lymphocytes showed decreases in IL-17 (T(eff))
      and Th1-like encephalitogenic cytokines IL-2 and IFN-gamma in the ACTH fed group
      compared to the mock fed group. Adoptive transfer of ACTH fed splenocytes into
      MOG immunized recipient mice with early clinical disease suppressed disease
      severity compared to splenocytes from mock fed donors. The protected recipients
      showed decreased splenic IL-17 (T(eff)) and Th1-like cytokine IFN-gamma and
      increased CNS secretion of immunoregulatory IL-4 and chemokine M-CSF. Splenic
      CD4+CD25+ FoxP3+ frequency doubled in ACTH fed compared to control fed mice.
      Increased immuno-regulatory IL-4 and M-CSF secreting cell populations is the
      mechanism of protection in adoptively protected recipients and reflects the
      direct action of ACTH on the immune system.

PMID- 21081249
TI  - A novel endoscopically placed stent to relieve glottic obstruction from bilateral
      vocal fold paralysis.
AB  - OBJECTIVE: Congenital bilateral vocal fold paralysis (BVP) is a rare but serious
      condition often requiring a tracheostomy to temporize the airway. In cases of
      idiopathic BVP, studies suggest waiting twelve months prior to laryngeal surgery
      because of a high rate of spontaneous recovery. Therefore a less invasive and
      reversible intervention would be optimal. A prospective study in a piglet model
      was undertaken to evaluate the efficacy of a novel spring-loaded stenting device
      designed to maintain laryngeal patency in an in vivo animal model of BVP.
      METHODS: Eight Yorkshire piglets had BVP induced by surgical division of the
      recurrent laryngeal nerves. Stents were endoscopically deployed between the
      arytenoid vocal processes. Animals were recovered and monitored for stridor,
      dietary intake, and weight gain. Animals were sacrificed after five days. Airway
      resistance using a calibrated manometer was measured at four time-points:
      baseline, BVP induction, stent insertion, and pre-sacrifice. RESULTS: Six of
      eight animals survived greater than five days with an average weight gain of
      1.9kg (p=0.003). Relative inspiratory resistance increased from baseline after
      inducing BVP (1.00 vs. 1.468, p=0.0315) and decreased to baseline levels with
      stent insertion (1.468 vs. 1.092, p=0.0238). Expiratory resistance was not
      significantly influenced by stage of measurement (p=0.236). Of the two animals
      not surviving the protocol, one had an unrelated anesthesia complication and the
      other a malpositioned stent. CONCLUSION: The novel stent was successful in
      relieving the inspiratory resistance associated with BVP, without compromising
      swallowing and daily function. This may hold promise in temporarily securing the
      pediatric airway in the setting of BVP.

PMID- 21081250
TI  - Acoustic rhinometry, spirometry and nitric oxide in relation to airway allergy
      and smoking habits in an adolescent cohort.
AB  - OBJECTIVE: This study aimed to analyze upper and lower airway function and the
      impact of smoking habits in a cohort of allergic and healthy adolescents. The
      influence of smoking habits on the outcomes of rhinitis and asthma is well
      documented, but only few reports are available showing smoke related upper airway
      impairment by rhinometric measurements, and none with focus on early changes in
      adolescents. METHODS: A cohort followed from infancy was re-examined at the age
      of 18 years concerning allergy development. Acoustic rhinometry (VOL2),
      spirometry (FEV(1)) and measurements of nitric oxide levels from the upper (nNO)
      and lower airways (eNO) were performed before and after physical exercise, and
      smoking habits were registered. RESULTS: Active smoking habits were reported by
      4/21 subjects suffering from allergic rhinitis, by 1/4 from probable allergic
      rhinitis, by 0/3 subjects with atopic dermatitis and by 2/10 healthy controls.
      Smoking habits were reported as daily by 2 and occasional by 5 of the 7 active
      smokers. VOL2 did not increase in smokers after exercise as in non-smokers,
      resulting in a post-exercise group difference (7.3+/-1.1cm(3) vs. 8.8+/-1.5cm(3);
      p=0.02), and FEV(1) values were lower in smokers compared to non-smokers (89+/-7%
      vs. 98+/-8%; p=0.02). The nNO and eNO levels were, however, only slightly reduced
      in smokers. Airway allergy was discerned only in subjects with current allergen
      exposure by increased eNO levels compared to healthy controls (41+/-44ppb vs.
      13+/-5ppb). The levels of VOL2, nNO and FEV(1) did not differentiate allergic
      subjects from healthy controls. CONCLUSIONS: Low levels of tobacco smoke exposure
      resulted in reduced airway functions in this adolescent cohort. Acoustic
      rhinometry and spirometry were found to be more sensitive methods compared to
      nitric oxide measurements in early detection of airway impairment related to
      smoke exposure. A possible difference in airway vulnerability between allergic
      and healthy subjects due to smoke exposure remains to be evaluated in larger
      study groups.

PMID- 21081251
TI  - Bosentan-sildenafil association in patients with congenital heart disease-related
      pulmonary arterial hypertension and Eisenmenger physiology.
AB  - OBJECTIVES: The aim of the present study was to evaluate the safety,
      tolerability, clinical and haemodynamic impact of add-on sildenafil in patients
      with congenital heart disease (CHD)-related pulmonary arterial hypertension (PAH)
      and Eisenmenger physiology after failure of oral bosentan therapy. METHODS:
      Thirty-two patients with CHD-related PAH (14 male, mean age 37.1 +/- 13.7 years)
      treated with oral bosentan underwent right heart catheterization (RHC) for
      clinical worsening. After RHC, all patients received oral sildenafil 20mg thrice
      daily in addition to bosentan. Clinical status, resting transcutaneous oxygen
      saturation (SpO(2)), 6-minute walk test (6MWT), serology and RHC were assessed at
      baseline (before add-on sildenafil) and after 6 months of combination therapy.
      RESULTS: Twelve patients had ventricular septal defect, 8 atrio-ventricular
      canal, 6 single ventricle, and 6 atrial septal defect. Twenty-eight/32 had
      Eisenmenger physiology and 4 (all with atrial septal defect) did not. All
      patients well tolerated combination therapy. After 6 months of therapy, an
      improvement in clinical status (WHO functional class 2.1 +/- 0.4 vs 2.9 +/- 0.3;
      P=0.042), 6-minute walk distance (360 +/- 51 vs 293 +/- 68 m; P=0.005), SpO(2) at
      the end of the 6MWT (72 +/- 10 vs 63 +/- 15%; P=0.047), Borg score (2.9 +/- 1.5
      vs 4.4 +/- 2.3; P=0.036), serology (pro-brain natriuretic peptide 303 +/- 366 vs
      760 +/- 943 pg/ml; P=0.008) and haemodynamics (pulmonary blood flow 3.4 +/- 1.0
      vs 3.1 +/- 1.2l/min/m(2), P=0.002; pulmonary vascular resistances index 19 +/- 9
      vs 24 +/- 16 WU/m(2), P=0.003) was observed. CONCLUSIONS: Addition of sildenafil
      in adult patients with CHD-related PAH and Eisenmenger syndrome after oral
      bosentan therapy failure is safe and well tolerated at 6-month follow-up,
      resulting in a significant improvement in clinical status, effort SpO(2),
      exercise tolerance and haemodynamics.

PMID- 21081252
TI  - Using mortality data for early detection of Classical Swine Fever in The
      Netherlands.
AB  - Early detection of the introduction of an infectious livestock disease is of
      great importance to limit the potential extent of an outbreak. Classical Swine
      Fever (CSF) often causes non-specific clinical signs, which can take considerable
      time to be detected. Currently, the disease can be detected by three main routes,
      that are all triggered by clinical signs. To improve the early detection of CSF
      an additional program, based on mortality data, aims to routinely perform PCR
      tests on ear notch samples from herds with a high(er) mortality. To assess the
      effectiveness of this new early detection system, we have developed a stochastic
      model that describes the virus transmission within a pig herd, the development of
      disease in infected animals and the different early detection programs. As virus
      transmission and mortality (by CSF and by other causes) are different for
      finishing pigs, piglets and sows, a distinction is made between these pig
      categories. The model is applied to an extensive database that contains all
      unique pig herds in The Netherlands, their herd sizes and their mortality reports
      over the CSF-free period 2001-2005. Results from the simulations suggest that the
      new early detection system is not effective in piglet sections, due to the high
      mortality from non-CSF causes, nor in sow sections, due to the low CSF-mortality.
      In finishing herds, the model predicts that the new early detection system can
      improve the detection time by two days, from 38 (27-53) days to 36 (24-51) days
      after virus introduction, when assuming a moderately virulent virus strain
      causing a 50% CSF mortality. For this result up to 5 ear notch samples per herd
      from 8 (0-13) finishing herds must be tested every workday. Detecting a source
      herd two days earlier could considerably reduce the number of initially infected
      herds. However, considering the variation in outcome and the uncertainty in some
      model assumptions, this two-day gain in detection time is too small to
      demonstrate a substantial effect of the new early detection system based on
      mortality data. But when the alertness of herd-owners and veterinarians
      diminishes during long CSF-free periods, the new early detection system might
      gain in effectiveness.

PMID- 21081253
TI  - In vivo virulence of commercial Saccharomyces cerevisiae strains with
      pathogenicity-associated phenotypical traits.
AB  - Two commercial Saccharomyces cerevisiae strains, a baker's strain and the bio
      therapeutic agent Ultralevure, have been proposed as a possible exogenous source
      of human colonization (de Llanos et al., 2004, 2006a). Moreover, these strains
      express phenotypical traits associated to pathogenicity (de Llanos et al.,
      2006b). Taking into account that both commercial preparations represent an
      important source of living S. cerevisiae cells we have performed an in vivo study
      to evaluate whether there is a potential safety risk to humans. Their virulence
      was compared with that of other commercial strains with less virulent traits, and
      with clinical isolates, using two murine models (BALB/c and DBA/2N mice). Burden
      determination in the brain and kidneys showed that the ability to disseminate,
      colonize and persist was manifested not only by clinical isolates but also by
      commercial strains. Among these, the baker's strain and Ultralevure were able to
      cause the death of BALB/c mice at rates similar to those shown by two of the
      clinical isolates. These results highlight the pathogenic potential of these
      strains and show that four-week-old BALB/c mice are an appropriate murine model
      to study the virulence of yeasts with low or moderate pathogenicity. Furthermore,
      we have shown the positive effect of an immunosuppressive therapy with
      cyclophosphamide in the virulence of the baker's strains and Ultralevure but not
      in the rest of the commercial strains under study. The data suggest that although
      S. cerevisiae has always been considered a GRAS microorganism, commercial
      preparations should include only those strains shown to be safe in order to
      minimize complications in risk groups.

PMID- 21081254
TI  - Consumption of raw vegetables and fruits: a risk factor for Campylobacter
      infections.
AB  - The purpose of this study was to determine the prevalence of Campylobacter in
      fresh vegetables and fruits at retail level in the Netherlands, and to estimate
      its implications on the importance of vegetables and fruits as risk factor for
      campylobacteriosis. Thirteen of the 5640 vegetable and fruit samples were
      Campylobacter positive, resulting in a prevalence of 0.23% (95% confidence
      interval (Cl): 0.12-0.39%). The prevalence of packaged products (0.36%, 95% Cl:
      0.17-0.66) was significantly higher than of unpackaged products (0.07; 95% Cl:
      0.01-0.27). No statistical differences were found between seasons. Combining the
      mean prevalence found in this study with data on the consumption of vegetables
      and fruits, an exposure of 0.0048 campylobacters ingested per person per day in
      the Netherlands by transmission via vegetables and fruits, was calculated. This
      exposure, as input in a Beta-Poisson dose-response model, resulted in an
      estimated number of 5.3*105 cases of infection with Campylobacter per year for
      the whole Dutch population. This constitutes the consumption of raw vegetables
      and fruits, especially when packaged, to be a risk factor for Campylobacter
      infections.

PMID- 21081255
TI  - Reduction of nitrobenzene in groundwater by iron nanoparticles immobilized in
      PEG/nylon membrane.
AB  - The highly reactive iron nanoparticles (NPs) immobilized in nylon membrane were
      synthesized and characterized, and the reduction of nitrobenzene (NB) in
      groundwater by the NPs was investigated. Environmental scanning electron
      microscopy (ESEM) images showed that the NPs distributed homogeneously on the
      membrane surface without agglomeration. X-ray diffraction (XRD) and X-ray
      photoelectron spectroscopy (XPS) analyses revealed that the NPs immobilized in
      membrane were mainly composed of Fe-oxides rather than zero-valent iron.
      Thermogravimetric (TG) analysis suggested that the weight percentage of the
      immobilized NPs and the oxygen introduced to the reacted sample after 80min
      reaction were about 18.5% and 13%, respectively. Moreover, Fourier transform
      infrared (FTIR) analysis further demonstrated the changes on the membrane surface
      after thermal grafting, NPs immobilizing and reacting for 80min. Using the
      reactive NPs immobilized in nylon membrane, NB in groundwater was rapidly and
      quantitatively decreased by 68.9% just in the first 20min, the Fe(2+) associated
      with the iron NPs immobilized in PEG/nylon66 membrane was mainly responsible for
      this reduction. The reaction appeared to follow pseudo-first-order kinetics and
      the rate constants increased upon decreasing the pH value. The samples we
      prepared exhibited good corrosion resistance for humic acid (HA) but had a short
      term performance for NB degradation. More so, the groundwater chemistry had a
      negative influence on the reactivity of membrane immobilized NPs.

PMID- 21081256
TI  - Nursing students and the issue of voice: a qualitative study.
AB  - AIMS AND OBJECTIVES: This paper reports the findings of part of a larger study
      that explored the empowerment of nursing students in clinical practice. The focus
      here is on the phenomenon of 'voice' and the extent to which nursing students are
      able to exercise voice during their clinical practice experiences. BACKGROUND:
      There is evidence to suggest that nursing students are 'silenced' in clinical
      practice and that they are unable to make their voices heard, even when they
      witness poor nursing practice. METHODS: This study explored the experiences of
      thirteen nursing students in the UK as they progressed through their
      undergraduate nursing programme. The study was underpinned by hermeneutic
      phenomenology. Data were generated through annual, semi-structured interviews and
      focus group discussions. FINDINGS: In situations that called for nursing students
      to 'speak up' they did one of two things: exit or voice. However, there was
      bridging of these actions in the form of 'negotiating voice'. DISCUSSION:
      Theoretically, findings of this study can be understood in relation to
      Hirschman's notions of 'exit and voice'. However, rather than being dichotomised
      extremes, an exit-voice continuum is proposed. CONCLUSIONS: Students are often
      silenced in clinical practice, but to overcome this they negotiate situations in
      an attempt to be heard. This paper provides new insight into the means by which
      nursing students can be supported to avoid the exit option, in favour of
      exercising voice.

PMID- 21081257
TI  - Associations of muscle depletion with health status. Another gender difference in
      COPD?
AB  - BACKGROUND & AIMS: Muscle mass depletion occurring in chronic obstructive
      pulmonary disease still leaves questions regarding its relation with health
      status. How health status should be conceived and assessed is a significant
      obstacle in answering these questions. This study tries to appoint which domains
      of health status are challenged by muscle depletion and evaluates evidence of
      gender difference. METHODS: 135 Patients enrolled in a cohort study with initial
      assessment of health status by the Nijmegen Integral Assessment Framework. In
      here 4 main domains and 16 sub-domains are recognized. These sub-domains were
      correlated with fat free mass index using baseline data. Associations of fat free
      mass and diffusion parameters with sex were elaborated. RESULTS: Muscle depletion
      occurred predominantly in those with low body mass index, and did not correlate
      with sub-domains of 3 main domains: Complaints, Functional Impairment and Quality
      of Life. In Physiological Functioning Hyperinflation correlated weakly. Diffusion
      capacity significantly correlated with fat free mass index in separate analyses
      of pulmonary function data. Interestingly, diffusion capacity was significantly
      lower in women than in men. CONCLUSIONS: Muscle depletion hardly affects health
      status in COPD. Physiological correlations, however, do exist, pointing to severe
      disease, especially emphysema, and female sex as important concomitant factors.

PMID- 21081258
TI  - Use of N-butyl-2-cyanoacrylate tissue glue in thoracic duct injury during neck
      dissection surgery.
AB  - Although thoracic duct injury is an uncommon complication of neck dissection, it
      can have a significant physiological and immunological impact on the patient's
      recovery as well as having more serious effects. We report a novel technique of
      using cyanoacrylate tissue glue for managing thoracic duct damage when this is
      noted at the time of neck dissection surgery. We have used this technique in four
      patients with no post-operative chyle leak or added complications.

PMID- 21081259
TI  - Carboxymethyl-beta-cyclodextrin conjugated magnetic nanoparticles as nano
      adsorbents for removal of copper ions: synthesis and adsorption studies.
AB  - A novel nano-adsorbent, carboxymethyl-beta-cyclodextrin modified Fe(3)O(4)
      nanoparticles (CMCD-MNPs) is fabricated for removal of copper ions from aqueous
      solution by grafting CM-beta-CD onto the magnetite surface via carbodiimide
      method. The characteristics results of FTIR, TEM, TGA and XPS show that CM-beta
      CD is grafted onto Fe(3)O(4) nanoparticles. The grafted CM-beta-CD on the
      Fe(3)O(4) nanoparticles contributes to an enhancement of the adsorption capacity
      because of the strong abilities of the multiple hydroxyl and carboxyl groups in
      CM-beta-CD to adsorb metal ions. The adsorption of Cu(2+) onto CMCD-MNPs is found
      to be dependent on pH and temperature. Adsorption equilibrium is achieved in 30
      min and the adsorption kinetics of Cu(2+) is found to follow a pseudo-second
      order kinetic model. Equilibrium data for Cu(2+) adsorption are fitted well by
      Langmuir isotherm model. The maximum adsorption capacity for Cu(2+) ions is
      estimated to be 47.2mg/g at 25  degrees C. Furthermore, thermodynamic parameters
      reveal the feasibility, spontaneity and exothermic nature of the adsorption
      process. FTIR and XPS reveal that Cu(2+) adsorption onto CMCD-MNPs mainly
      involves the oxygen atoms in CM-beta-CD to form surface-complexes. In addition,
      the copper ions can be desorbed from CMCD-MNPs by citric acid solution with 96.2%
      desorption efficiency and the CMCD-MNPs exhibit good recyclability.

PMID- 21081260
TI  - Mental disorders after burn injury: a prospective study.
AB  - OBJECTIVE: To prospectively investigate variations in prevalences of mental
      disorders after burn, and correlation between burn severity and mental disorders
      among hospitalized burn patients. METHOD: A cohort of 107 consecutive acute adult
      burn patients was examined with structured diagnostic interview (SCID-I) at
      baseline, and 92 patients (86%) at 6 months after injury. Prevalences of mental
      disorders for the whole 6-month follow-up period, plus 1-month point prevalences
      in acute care and in a second 6-month interview were assessed, and the two point
      prevalences were compared. Burn severity was estimate by %TBSA. RESULTS: During
      the 6-month follow-up 55% (51/92) of burn patients had at least one mental
      disorder, including 12% (11/92) with post-traumatic stress disorder (PTSD). In a
      multinomial regression, %TBSA exposure independently and strongly predicted risk
      for mental disorders, especially for anxiety disorders and delirium. The overall
      point prevalence of mental disorders decreased significantly (p=0.036) from acute
      care (45%) to 6 months (33%). CONCLUSIONS: After burn, more than half of the
      patients suffer from some type of mental disorder, but the prevalence declines
      over time after the acute phase. The disorders are not limited to depression and
      PTSD. A strong relationship likely exists between burn severity and some post
      burn mental disorders.

PMID- 21081261
TI  - Mediating processes of two communication interventions for breast cancer
      patients.
AB  - OBJECTIVE: Test whether three mediating processes of Self-Determination Theory
      are involved in intervention effects on quality of life for breast cancer
      patients. METHODS: A randomized clinical trial recruited newly diagnosed breast
      cancer patients for 6 months of (1) Internet training and access, (2) access to
      an integrated eHealth system for breast cancer (CHESS), (3) a series of phone
      conversations with a Human Cancer Information Mentor, or (4) both (2) and (3).
      RESULTS: This paper reports results after the initial 6 weeks of intervention, at
      which point patients in the combined condition had higher quality of life scores
      than those in the other three conditions. All three Self-Determination Theory
      constructs (autonomy, competence, and relatedness) mediated that effect as
      hypothesized. In addition, the single-intervention groups were superior to the
      Internet-only group on relatedness, though perhaps this was too soon for that to
      carry through to quality of life as well. CONCLUSIONS: The SDT constructs do
      mediate these interventions' effects. PRACTICE IMPLICATIONS: Intervention design
      can profitably focus on enhancing autonomy, competence and relatedness.

PMID- 21081262
TI  - Visco-fracture technique for soft lens cataract removal.
AB  - We describe a visco-fracture technique for soft nucleus phacoemulsification.
      Following continuous curvilinear capsulorhexis, cortical cleavage
      hydrodissection, and hydrodelineation, an ophthalmic viscosurgical device (OVD)
      is delivered into the eye through a hydrodissection cannula. A small amount of
      pressure is used to introduce the cannula into the nucleus. The OVD is then
      gently injected, creating a small central crack. The surgeon can explore this
      initial crack, enlarging it in both directions to create a complete fracture of
      the nucleus. The maneuver can be repeated by rotating the nucleus 90 degrees,
      creating additional fractures in the same way. Each quadrant can then be
      emulsified using an auxiliary second instrument. FINANCIAL DISCLOSURE: Neither
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 21081263
TI  - Triple-post lid speculum: Maximizing exposure for cataract surgery.

PMID- 21081264
TI  - Are young adults with special needs ready for the physical work demands?
AB  - Youth and Adolescents with Special Needs (YASN) face many challenges during
      transition into employment. Although most of their physical challenges are
      secondary, yet they call for attention since most of them are hired for blue
      collar jobs. Functional Capacity Evaluation (FCE) should be adapted to prepare
      them addressing the physical job-demands, and maintain their jobs effectively and
      safely. The current pilot study aims to demonstrate the use of standard (FCE) in
      order to assess performance of basic generic physical activities conducted by
      YASN, as part of transition to work program. Specifically, it compared subtests
      of the Physical Work Performance Evaluation of YASN (N = 13) with matched control
      group (YA) (N = 13). Results revealed slower and reduced performance among YASNs
      than YA, in basic job demands, like dynamic strength, hand strength, and fine
      motor skills. Implications and recommendations for research and transition to
      work practice in the educational setting are discussed.

PMID- 21081265
TI  - Cyclooxygenase-2 activity is important in craniofacial fracture repair.
AB  - The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone
      repair after craniofacial fracture in mice. A 4-mm fracture was created in the
      parietal bone of 8-week-old male COX-2 wild-type (COX-2(+/+)) and knockout (COX
      2(-/-)) mice. Ribonucleic acid was extracted from the fractured bone and
      analysed. For morphological and histological analysis, the mice were killed 8 and
      12 weeks after treatment, and sections were prepared. Three-dimensional computed
      tomography was performed, and the sections were stained with hematoxylin-eosin
      for histological examination. Expression of COX-2 messenger ribonucleic acid was
      induced in COX-2(+/+) mice, but not in COX-2(-/-) mice. Ossification at the
      fracture site was almost complete 12 weeks after fracture in COX-2(+/+) mice. In
      COX-2(-/-) mice, incomplete union had occurred at the fracture site. In both
      types of mice, the fracture site contained no cartilaginous tissue, and the
      callus formed from the periosteal side. These results suggest that COX-2 plays an
      important role in craniofacial fracture repair and that COX-2-selective non
      steroidal anti-inflammatory drugs might interfere with fracture repair of the
      membranous viscerocranium in the clinical setting.

PMID- 21081266
TI  - Prediction of a single psychotic episode: a 7.5-year, prospective study in first
      episode psychosis.
AB  - BACKGROUND: Around 20% of patients who suffer from psychosis will experience a
      single psychotic episode (SPE), but relatively little is known about the
      characteristics and predictors for this group of patients. This study sought to:
      1) characterise the subgroup of first-episode psychosis (FEP) patients who
      experienced a SPE over a 7.5-year follow-up; and 2) to identify significant
      predictors for this subgroup independent of potential confounders. METHODS: A
      representative sample of 413 FEP patients treated at a specialist early psychosis
      service were assessed at baseline and followed-up for 7.5 years. Binary logistic
      regression models were employed to investigate univariate and adjusted
      associations between baseline predictors and experiencing a SPE. Results were
      adjusted for the influence of known prognostic factors for psychosis. RESULTS:
      Follow-up data was available for 274 participants. Forty-six (16.5%) achieved
      clinical remission and experienced no recurrence over the follow-up period.
      Duration of untreated psychosis (DUP) shorter than 60 days (OR=3.89, p=0.007),
      more rapid response to antipsychotic treatment (OR=0.33, p=0.019) and no parental
      loss (OR=5.25, p=0.045) significantly predicted a SPE. The association remained
      significant after controlling for potential confounders. CONCLUSIONS: Early
      treatment (within two months of onset of psychotic symptoms) and social support
      significantly reduce vulnerability to subsequent psychotic episodes. Future
      studies need to investigate the interplay between biological factors (i.e.
      sensitized dopaminergic system), environmental variables (i.e. exposure to
      trauma, stigma and discrimination), and psychological attributes (i.e. cognitive
      schemata) in order to elucidate the processes underlying the vulnerability to
      recurrent psychotic episodes.

PMID- 21081267
TI  - The hsp27kD heat shock protein and p38-MAPK signaling are required for regular
      epidermal differentiation.
AB  - BACKGROUND: In human epidermal keratinocytes the expression of hsp27 is closely
      related to differentiation in vitro and in situ. OBJECTIVE: We aimed to gain
      further insight into the role of hsp27 in epidermal differentiation by specific
      inhibition through siRNA and inhibition of p38-MAPK, the key enzyme of hsp27
      phosphorylation. METHODS: Normal human keratinocytes (KC) and organotypic skin
      cultures (SE-skin equivalents) were used. Expression and phosphorylation of hsp27
      was inhibited in these models by siRNA and SB203580, a specific inhibitor of p38
      MAPK, respectively. Modification of morphology and expression of hsp27 and other
      differentiation associated proteins was investigated by immunofluorescence,
      western blot, and RT-PCR. RESULTS: Inhibition of p38-MAPK resulted in a
      downregulation of hsp27 in KC and SE. Additionally, in the presence of SB203580
      Ca(2+) induced expression of pro-filaggrin and loricrin was inhibited at the
      protein level and expression of filaggrin, keratin 10, and transglutaminase 1 at
      the mRNA level. Addition of SB203580 to SE, as well as hsp27 knockdown in this
      model resulted in identical patterns of irregular differentiation, disturbance of
      epidermal layers, and delayed expression of K10. CONCLUSION: These results
      provide evidence that the expression of hsp27 and its phosphorylation by p38-MAPK
      are required for keratinocyte differentiation and for the formation of a
      regularly stratified epidermis.

PMID- 21081268
TI  - Gray matter decrease distribution in the early stages of Anorexia Nervosa
      restrictive type in adolescents.
AB  - Few studies have used Voxel-Based Morphometry (VBM) to examine brain structure in
      Anorexia Nervosa patients. The purpose of the present study was to investigate a
      sample of Anorexia Nervosa restrictive type (AN-r) adolescent patients in the
      early stages of the illness, using VBM in order to characterize morphometric gray
      matter (GM) changes. Participants were 16 AN-r female patients (with no other
      psychiatric disorders) whose AN-r had been in progress for less than 12 months
      and 16 age-matched healthy female subjects. High-resolution T1-weighted magnetic
      resonance images were preprocessed according to the optimized VBM method, and
      statistically analyzed. The analyses revealed a significant global GM decrease in
      the AN-r patients; furthermore, a significant region-specific decrease in GM
      volume was found bilaterally in the middle cingulate cortex, the precuneus, and
      the inferior and superior parietal lobules. The significant early GM decrease in
      the aforementioned regions in AN-r adolescent patients suggests that there might
      be a region-specific GM vulnerability that could play a role in the
      pathophysiology of the disease. Given that these regions are also involved in the
      manipulation of mental images and the mental representation of the self, this
      might explain the presence of a distorted body image in these patients.

PMID- 21081269
TI  - Electropolymerization molecularly imprinted polymer (E-MIP) SPR sensing of drug
      molecules: pre-polymerization complexed terthiophene and carbazole electroactive
      monomers.
AB  - A novel chemosensitive ultrathin film with high selectivity was developed for the
      detection of naproxen, paracetamol, and theophylline using non-covalent
      electropolymerized molecular imprinted polymers (E-MIP). A series of
      monofunctional and bifunctional H-bonding terthiophene and carbazole monomers
      were compared for imprinting these drugs without the use of a separate cross
      linker. A key step is the fast and efficient potentiostatic method of washing the
      template, which facilitated enhanced real-time sensing by surface plasmon
      resonance (SPR) spectroscopy. Various surface characterizations (contact angle,
      ellipsometry, XPS, AFM) of the E-MIP film verified the templating and release of
      the drug from the cross-linked conducting polymer film.

PMID- 21081271
TI  - A folding-based electrochemical aptasensor for detection of vascular endothelial
      growth factor in human whole blood.
AB  - We herein report a folding-based electrochemical DNA aptasensor for the detection
      of vascular endothelial growth factor (VEGF) directly in complex biological
      samples, including blood serum and whole blood. The electrochemical signal
      generation is coupled to a large, target-induced conformational change in a
      methylene blue-modified and surface immobilized anti-VEGF aptamer. The sensor is
      sensitive, selective and essentially reagentless: we can readily detect VEGF down
      to 5 pM (190 pg/mL) directly in 50% blood serum. Similar to other aptasensors of
      this class, the VEGF sensor is also regenerable and reusable. In addition, the
      sensor performs comparably well even when fabricated on a gold-plated screen
      printed carbon electrode and can potentially be implemented as a cost-effective,
      single-use biosensor for diseases diagnosis and therapy monitoring. The
      exceptional sensitivity, selectivity, and reusability of this electrochemical
      aptasensor platform suggest it may be a promising strategy for a wide variety of
      sensing applications.

PMID- 21081270
TI  - A screen-printed microband glucose biosensor system for real-time monitoring of
      toxicity in cell culture.
AB  - Microband biosensors, screen-printed from a water-based carbon ink containing
      cobalt phthalocyanine redox mediator and glucose oxidase (GOD) enzyme, were used
      to monitor glucose levels continuously in buffer and culture medium. Five
      biosensors were operated amperometrically (E(app) of +0.4V), in a 12-well tissue
      culture plate system at 37 degrees C, using a multipotentiostat. After 24 h, a
      linear calibration plot was obtained from steady-state current responses for
      glucose concentrations up to 10 mM (dynamic range 30 mM). Within the linear
      region, a correlation coefficient (R(2)) of 0.981 was obtained between biosensor
      and spectrophotometric assays. Over 24 h, an estimated 0.15% (89 nmol) of the
      starting glucose concentration (24 mM) was consumed by the microbiosensor. The
      sensitivity of the biosensor response in full culture medium was stable between
      pHs 7.3 and 8.4. Amperometric responses for HepG2 monolayer cultures decreased
      with time in inverse proportionality to cell number (for 0 to 10(6) cell/ml), as
      glucose was being metabolised. HepG2 3D cultures (spheroids) were also shown to
      metabolise glucose, at a rate which was independent of spheroid age (between 6
      and 15 days). Spheroids were used to assay the effect of a typical hepatotoxin,
      paracetamol. At 1 mM paracetamol, glucose uptake was inhibited by 95% after 6 h
      in culture; at 500 MUM, around 15% inhibition was observed after 16 h. This
      microband biosensor culture system could form the basis for an in vitro toxicity
      testing system.

PMID- 21081272
TI  - Rapid DNA detection by interface PCR on nanoparticles.
AB  - A novel, rapid DNA detection method based on fluorescence quenching of quantum
      dots (QDs) by gold nanoparticles (GNPs) through polymerase chain reaction (PCR)
      was developed. In proof-of-concept experiments, the length of the amplicon DNA
      ranging from 152 to 1003 base pairs (bp) could be determined based on quenched
      fluorescence intensity with 136 bp as the lower limit of effective range. And the
      real sample detections were also achieved successfully by this developed method.
      Therefore, this DNA detection method has the potential to be the powerful gene
      diagnostic tool.

PMID- 21081273
TI  - Fiber optic monooxygenase biosensor for toluene concentration measurement in
      aqueous samples.
AB  - Measurements of pollutants such as toluene are critical for the characterization
      of contaminated sites and for the monitoring of remediation processes and
      wastewater treatment effluents. Fiber optic enzymatic biosensors have the
      potential to provide cost-effective, real time, continuous, in situ measurements.
      In this study, a fiber optic enzymatic biosensor was constructed and
      characterized for the measurement of toluene concentrations in aqueous solutions.
      The biological recognition element was toluene ortho-monooxygenase (TOM),
      expressed by Escherichia coli TG1 carrying pBS(Kan)TOM, while an optical fiber
      coated with an oxygen-sensitive ruthenium-based phosphorescent dye served as the
      transducer. Toluene was detected based on the enzymatic reaction catalyzed by
      TOM, which resulted in the consumption of oxygen and changes in the
      phosphorescence intensity. The biosensor was found to have a limit of detection
      of 3 MUM, a linear signal range up to 100 MUM, and a response time of 1 h. The
      performance was reproducible with different biosensors (RSD=7.4%, n=8). The
      biosensor activity declined with each measurement and with storage time,
      particularly at elevated temperatures. This activity loss could be partially
      reversed by exposure to formate, suggesting that NADH consumption was the primary
      factor limiting lifetime. This is the first report of an enzymatic toluene sensor
      and of an oxygenase-based biosensor. Since many oxygenases have been reported,
      the design concept of this oxygenase-based biosensor has the potential to broaden
      biosensor applications in environmental monitoring.

PMID- 21081275
TI  - Repeatability of the modified Oxford foot model during gait in healthy adults.
AB  - BACKGROUND: The Oxford foot model (OFM) is a multi-segment model for calculating
      hindfoot and forefoot motion. Limited information is available regarding the
      repeatability and error of this model in adults. Therefore the purpose of this
      study was to assess the intra-tester reliability of OFM hindfoot and forefoot
      gait kinematics in adults at initial contact (IC) and toe-off (TO). METHODS:
      Seventeen healthy adults (age=25.1+/-4.8 years, height=1.75+/-0.10m,
      weight=74.0+/-12.4kg) were tested on a single visit, during which 1 examiner
      recorded 2 sessions. For each session, 10 walking trials were recorded using a 12
      camera motion analysis system (Vicon, Oxford, UK). Markers were removed and re
      applied between sessions. Dynamic hindfoot and forefoot angles were calculated
      both with and without referencing to neutral stance (assuming neutral stance
      angles are zero in all planes). Using the 10 trial average, intraclass
      correlation coefficients (ICC(2,k)) and standard errors of the measurement were
      calculated for each reference condition, anatomical plane, and joint (hindfoot,
      forefoot). RESULTS: Referencing to neutral stance resulted in good reliability
      (ICC>=0.83) and small error (<=2.45 degrees ) for hindfoot and forefoot angle in
      all planes. Without referencing to neutral stance, sagittal and transverse plane
      reliability were also good (ICC>=0.90) and error small (<=3.14 degrees );
      however, frontal plane reliability was poor (ICC<=0.77), with large error (>=4.86
      degrees ). DISCUSSION: Our results show that overall the OFM is reliable during
      adult gait. Reliability for adults is higher than previously reported in
      children. Referencing joint angles to neutral stance decreased error by up to 2
      degrees  from previous reports.

PMID- 21081274
TI  - Taming the complexity of protein folding.
AB  - Protein folding is an important problem in structural biology with significant
      medical implications, particularly for misfolding disorders like Alzheimer's
      disease. Solving the folding problem will ultimately require a combination of
      theory and experiment, with theoretical models providing a comprehensive view of
      folding and experiments grounding these models in reality. Here we review
      progress towards this goal over the past decade, with an emphasis on recent
      theoretical advances that are empowering chemically detailed models of folding
      and the new results these technologies are providing. In particular, we discuss
      new insights made possible by Markov state models (MSMs), including the role of
      non-native contacts and the hub-like character of protein folded states.

PMID- 21081276
TI  - Post-myocardial infarction left ventricular myocyte remodeling: are there gender
      differences in rats?
AB  - BACKGROUND: Previous studies have shown gender differences in left ventricular
      remodeling after myocardial infarction. Results are varied, however, and
      reliable, comprehensive data for changes in cardiac myocyte shape are not
      available. METHODS: Young adult female and male Sprague-Dawley rats were used in
      this study and randomly assigned to the myocardial infarction and sham myocardial
      infarction groups. Myocardial infarction was produced by ligation of the left
      descending coronary artery. Four weeks after surgery, left ventricular
      echocardiography and hemodynamics were performed before isolating myocytes for
      size determination. RESULTS: In general, left ventricular functional changes
      after myocardial infarction were comparable. Females developed slightly, but
      significantly, more left ventricular hypertrophy than males, and this was
      reflected by the relative increases in left ventricular myocyte volume. In both
      males and females, however, myocyte hypertrophy was due exclusively to
      lengthening of myocytes with no change in myocyte cross-sectional area.
      CONCLUSIONS: This study demonstrates that post-myocardial infarction changes in
      LV function and myocyte remodeling are remarkably similar in young adult male and
      female rats.

PMID- 21081277
TI  - A rare cardiac neoplasm: case report of cardiac epithelioid angiosarcoma.
AB  - Primary cardiac angiosarcoma is a rare neoplasm and the epithelioid variant is
      exceedingly rare. We report a case of an epithelioid angiosarcoma that involved
      the right atrium and aorta of a 47-year-old male. The patient presented with
      atrial fibrillation and presyncopal spells. Following clinical evaluation,
      including computed tomography scan and trans-esophageal echocardiography, the
      neoplasm was surgically removed. It was a poorly differentiated malignant
      neoplasm composed of medium-sized epithelioid cells with a moderate amount of
      amphophilic cytoplasm. Immunohistochemical staining, including positive staining
      for CK22, AE1/AE3, melan-A, vimentin, and CD31, indicated the neoplasm was best
      categorized as an epithelioid angiosarcoma.

PMID- 21081278
TI  - Crop genome sequencing: lessons and rationales.
AB  - 2010 marks the 10th anniversary of the completion of the first plant genome
      sequence (Arabidopsis thaliana). Triggered by advancements in sequencing
      technologies, many crop genome sequences have been produced, with eight published
      since 2008. To date, however, only the rice (Oryza sativa) genome sequence has
      been finished to a quality level similar to that of the Arabidopsis sequence.
      This trend to produce draft genomes could affect the ability of researchers to
      address biological questions of speciation and recent evolution or to link
      sequence variation accurately to phenotypes. Here, we review the current crop
      genome sequencing activities, discuss how variability in sequence quality impacts
      utility for different studies and provide a perspective for a paradigm shift in
      selecting crops for sequencing in the future.

PMID- 21081279
TI  - Assessment of patient and practitioner satisfaction with BiotrueTM multi-purpose
      solution for contact lenses.
AB  - PURPOSE: Consumer product companies often use in-home studies to gain consumer
      insights on product performance. Satisfaction surveys completed in the office
      have been shown to overestimate satisfaction ratings. The purpose of this study
      was to evaluate the consumer acceptance of a novel multi-purpose solution (Bausch
      & Lomb Biotrue multi-purpose solution) through the use of a unique Internet
      survey and a measurement of practitioner satisfaction through in-office
      evaluations. METHODS: Contact lens users were converted to an unbranded,
      investigational-labeled Biotrue multi-purpose solution. Independent practitioners
      from 15 investigational sites enrolled patients. Following 7 days of use,
      subjects completed an Internet survey to capture their perspectives regarding the
      product. After 2 weeks of use, the investigators exited the subjects. RESULTS: Of
      the 300 subjects enrolled, 291 (97%) completed the Internet survey. Ninety
      percent rated Biotrue multi-purpose solution "excellent," "very good," or "good"
      for overall opinion. Significantly more subjects rated Biotrue multi-purpose
      solution better than their habitual product. Use of Biotrue multi-purpose
      solution did not affect the fitting characteristics (centration/movement) or
      surface wetting of the lens. Throughout the evaluation, there were no adverse
      events reported. Slit lamp examinations revealed that 99.2% of eyes had minimal
      findings (no findings or trace or mild findings). With 600 eyes enrolled in the
      study, practitioners agreed that 95.2% of the eyes appeared healthy throughout
      the study. CONCLUSIONS: Use of Internet surveys can be an effective method to
      gain patient perspectives regarding new products dispensed by eye care
      practitioners. There was a high level of satisfaction with Biotrue multi-purpose
      solution.

PMID- 21081280
TI  - Correlations between refractive error and biometric parameters in human eyes
      using the LenStar 900.
AB  - PURPOSE: To investigate the relationship between refractive error and ocular
      biometry in healthy subjects using a new optical low coherence reflectometry
      device. METHODS: Biometric measurements were obtained with a LenStar LS 900 (Haag
      Streit, Switzerland) on one eye of 70 phakic subjects (mean +/- SD age; 29 +/- 9
      years). Forty myopes and 30 non-myopes (best sphere range -9.63 D to +0.63 D)
      were included. Outcome measures were compared for the two groups using one way
      between groups ANOVA. These included; keratometry, central corneal thickness,
      iris width, anterior chamber depth, pupil diameter, lens thickness, axial length
      and retinal thickness. No mydriatic or cycloplegic agents were used. RESULTS:
      There were significant differences between groups for keratometry readings (p =
      0.021 and p = 0.038 for steep and flat k readings respectively), anterior chamber
      depth (p = 0.001), lens thickness (p = 0.026) and axial length (p<0.001). As
      expected significant correlations were found between spherical equivalent power
      and axial length (Pearson product-moment correlation r = -0.75, p<0.001) and
      between spherical equivalent power and anterior chamber depth (r = -0.29, p =
      0.018). Anterior chamber depth and pupil diameter decreased with age (r = -0.429,
      p<0.001 and r = -0.386, p = 0.001 respectively) whereas lens thickness increased
      with age (r = 0.618, p < 0.001). CONCLUSIONS: Our data showed significant
      differences between myopes and non-myopes for the key biometric parameters
      assessed and provides information about the relationships between these biometric
      parameters and age. The results, coupled with a unique ability to image and
      analyse the ocular structures non-invasively make the LenStar a promising new
      instrument for ocular evaluation in research and clinical practice.

PMID- 21081281
TI  - Alteration of blue pigment in artificial iris in ocular prosthesis: effect of
      paint, drying method and artificial aging.
AB  - The artificial iris is the structure responsible for the dissimulation and
      aesthetics of ocular prosthesis. The objective of the present study was to
      evaluate the color stability of artificial iris of microwaveable polymerized
      ocular prosthesis, as a function of paint type, drying method and accelerated
      aging. A total of 40 discs of microwaveable polymerized acrylic resin were
      fabricated, and divided according to the blue paint type (n = 5): hydrosoluble
      acrylic, nitrocellulose automotive, hydrosoluble gouache and oil paints. Paints
      where dried either at natural or at infrared light bulb method. Each specimen was
      constituted of one disc in colorless acrylic resin and another colored with a
      basic sclera pigment. Painting was performed in one surface of one of the discs.
      The specimens were submitted to an artificial aging chamber under ultraviolet
      light, during 1008 h. A reflective spectrophotometer was used to evaluate color
      changes. Data were evaluated by 3-way repeated-measures ANOVA and the Tukey HSD
      test (alpha = 0.05). All paints suffered color alteration. The oil paint
      presented the highest color resistance to artificial aging regardless of drying
      method.

PMID- 21081282
TI  - Terbium (III) chelate complexes as fluorescence energy transfer donor in the
      determination of formaldehyde in aqueous solutions.
AB  - The sensitized fluorescence intensity of the terbium (III) ion can be notably
      enhanced in the presence of sodium hexametaphosphate (SHMP). Based on this, water
      soluble Tb-SHMP chelate complexes were synthesized in aqueous solutions, and
      characterized by spectrofluorometry. 6-Mercapto-5-triazole[4,3-b]-S-tetrazine was
      generated by the quantitative reaction of HCHO with 4-amino-3-hydrazino-5
      mercapto-1,2,4-triazole under alkaline conditions at room temperature. The
      spectral overlap between the emission of Tb-SHMP chelate complexes and absorption
      of 6-mercapto-5-triazole[4,3-b]-S-tetrazine meets the prerequisite for
      fluorescence energy transfer. Based on this, a novel efficient fluorescence
      energy transfer system between Tb-SHMP chelate complexes as donor and 6-mercapto
      5-triazole[4,3-b]-S-tetrazine as acceptor was developed for the determination of
      HCHO in aqueous solutions. Under the optimal experimental conditions, this method
      is capable of detecting HCHO concentrations from 2.06*10(-5) to 6.18*10(-3) mg
      mL(-1) and the limit of detection was 7.11*10(-6) mg mL(-1). Compared with other
      general methods for the determination of HCHO, the proposed method improved the
      sensitivity and selectivity. Moreover, the proposed method was successfully
      applied to the determination of HCHO in water samples.

PMID- 21081283
TI  - Structural studies and anticancer activity of a novel (N6O4) macrocyclic ligand
      and its Cu(II) complexes.
AB  - A novel (N6O4) macrocyclic ligand (L) and its Cu(II) complexes have been prepared
      and characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic,
      and conductivity measurements. Quantum chemical calculations have also been
      carried out at B3LYP/6-31+G(d,p) to study the structure of the ligand and one of
      its complexes. The results show a novel macrocyclic ligand with potential amide
      oxygen atom, amide and amine nitrogen atoms available for coordination. Distorted
      square pyramidal ([Cu(L)Cl]Cl.2.5H2O (1), [Cu(L)NO3]NO(3).3.5H2O (2), and
      [Cu(L)Br]Br.3H2O (4) and octahedral ([Cu(L)(OAc)2].5H2O (3)) geometries were
      proposed. The EPR data of 1, 2, and 4 indicate d1x2(-y)2 ground state of Cu(II)
      ion with a considerable exchange interaction. The measured cytotoxicity for L and
      its complexes (1, 2) against three tumor cell lines showed that coordination
      improves the antitumor activity of the ligand; IC50 for breast cancer cells are
      ~8.5, 3, and 4 MUg/mL for L and complexes (1) and (2), respectively.

PMID- 21081284
TI  - Integrated lysis procedures reduce extraction biases of microbial DNA from
      mangrove sediment.
AB  - Sufficient lysis of soil or sediment microbes is a critical step for analyzing
      microbial community structures and for preparing metagenomic DNA libraries. The
      present study compared lysis methods for recovering archaeal, bacterial,
      actinomycete, and fungal DNAs from a mangrove sediment sample. PCR results showed
      that individual procedures using SDS, lysozyme, sonication, freeze-thaw,
      microwave, and vigorous shaking could extract archaeal or bacterial DNA but
      failed for actinomycetes or fungi cells. In comparison, an integrated lysis
      procedure using SDS, lysozyme, and vigorous shaking successfully obtained fungal
      DNA, and a combination of SDS, lysozyme, vigorous shaking, and microwave
      treatments recovered DNA from actinomycetes. Denaturing gradient gel
      electrophoresis (DGGE) results showed that although single lysis procedures can
      lyse bacterial DNA, all of them assessed the indigenous bacterial community
      structure with significant biases. The integrated lysis protocols described in
      the present study could be useful for extracting DNA from various types of
      sediments.

PMID- 21081285
TI  - Steam pretreatment and fermentation of the straw material "Paja Brava" using
      simultaneous saccharification and co-fermentation.
AB  - Pretreatment, enzymatic hydrolysis and simultaneous saccharification and
      fermentation (SSF) of the South American straw material Paja Brava were
      investigated. Suitable process conditions for an SO2-catalyzed steam pretreatment
      of the material were determined and assessed by enzymatic digestibility of
      obtained fiber slurries for 72 h at a water insoluble solids (WIS) content of 2%.
      The best pretreatment conditions obtained (200  degrees C, 5 min holding time and
      2.5% SO2) gave an overall glucose yield following enzymatic hydrolysis of more
      than 90%, and a xylose yield of about 70%. Simultaneous saccharification and co
      fermentation of glucose and xylose (SSCF) of the pretreated material using the
      xylose-fermenting strain Saccharomyces cerevisiae TMB3400 was examined at WIS
      contents between 5% and 10%. In agreement with previous studies on other
      materials, the overall ethanol yield and also the xylose conversion decreased
      somewhat with increasing WIS content in the SSCF. In batch SSCF, the xylose
      conversion obtained was almost 100% at 5% WIS content, but decreased to 69% at
      10% WIS. The highest ethanol concentration obtained for a WIS content of 10% was
      about 40 g/L, corresponding to a yield of 0.41 g/g in a fed-batch SSCF. The Paja
      Brava material has previously been found difficult to hydrolyze in a dilute-acid
      process. However, the SSCF results obtained here show that similar sugar yields
      and fermentation performance can be expected from Paja Brava as from materials
      such as wheat straw, corn stover or sugarcane bagasse.

PMID- 21081286
TI  - Pressurized liquid method for fucoxanthin extraction from Eisenia bicyclis
      (Kjellman) Setchell.
AB  - Optimization of extraction conditions for fucoxanthin from brown algae Eisenia
      bicyclis was investigated through a pressurized liquid extraction (PLE) method
      and statistical experimental design. The process was optimized by Plackett-Burman
      design at first step to screen the most important variables in the extraction of
      fucoxanthin, and subsequently central composite design was applied to attain the
      optimum conditions of the selected factors for fucoxanthin extraction. Two
      factors, temperature and ethanol concentration, significantly influenced the
      extraction efficiency of fucoxanthin at 95% level (P<0.05). The maximum predicted
      value of fucoxanthin extraction was 0.42 mg/g at 110  degrees C and 90% ethanol.
      The validation of the model was verified by triplicate experiments under the
      optimal conditions. The results demonstrated that the statistical strategy was
      successfully applied for optimization of PLE method for fucoxanthin extraction
      and that PLE can be a powerful method to extract fucoxanthin from E. bicyclis.

PMID- 21081288
TI  - Rapid and sensitive LC-MS/MS method for determination of felbamate in mouse
      plasma and tissues and human plasma.
AB  - Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a second generation
      antiepileptic drug used to treat seizures refractory to other antiepileptic
      drugs. With approximately 3500 new patients exposed annually, several important
      pharmacologic interaction questions remain unanswered necessitating the need for
      rapid and accurate methods of felbamate analysis in biological matrices. To this
      end, a rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was
      developed for the measurement of felbamate in mouse plasma and tissues and human
      plasma. Plasma (100 MUL) and tissues homogenates (100 MUL of 100 mg/mL) were
      spiked with internal standard (carisoprodol) prior to protein precipitation with
      acetonitrile. Samples were chromatographed on a XBridge Phenyl, 2.5 MUm, 4.6
      mm*50 mm column with quantitation by internal standard reference monitoring of
      the ion transitions m/z 239->117 for felbamate and m/z 261->176 for carisoprodol.
      Calibration curves were linear from 2.5 to 500 ng/mL in mouse or human plasma and
      25-5000 pg/mg in tissue homogenates. Recoveries were greater than 97% for plasma
      and homogenates with accuracies >92% in any of the mouse matrices and >88% in
      human plasma. Comparable accuracies and precision were found with and without the
      use of the internal standard in preparation of the calibration curves and suggest
      that the internal standard may not be required.

PMID- 21081289
TI  - Simultaneous determination of pregnenolone and 17alpha-hydroxypregnenolone by
      semi-micro high-performance liquid chromatography with an immobilized cholesterol
      oxidase as a pre-column reactor: application to bovine adrenal fasciculata cells.
AB  - A method for the simultaneous determination of pregnenolone and 17alpha
      hydroxypregnenolone by high-performance liquid chromatography with an immobilized
      cholesterol oxidation enzyme reactor was developed. Pregnenolone and 17alpha
      hydroxypregnenolone were converted to progesterone and 17alpha
      hydroxyprogesterone, respectively, by the immobilized enzyme packed into the
      reactor column, and could thus be monitored by UV absorption at 240 nm. The
      calibration curves for pregnenolone and 17alpha-hydroxypregnenolone were linear
      in the range of 0.4-10 and 0.3-10 MUg/ml with a correlation coefficient of 0.9993
      and 0.9998, respectively. The detection limit at a signal-to-noise ratio of 3 was
      0.12 and 0.08 MUg/ml for pregnenolone and 17alpha-hydroxypregnenolone,
      respectively. The conversion rate of pregnenolone to progesterone and 17alpha
      hydroxypregnenolone to 17alpha-hydroxyprogesterone was 90.6% and 99.3%,
      respectively. Intra-day and inter-day precision (in terms of percentage
      coefficient of variation) were less than 9.3%, with accuracy greater than 94.8%.
      This method was successfully applied to the simultaneous determination of
      pregnenolone and 17alpha-hydroxypregnenolone secreted into the culture medium of
      bovine adrenal fasciculata cells and of both analytes produced within the cells.

PMID- 21081290
TI  - Enantioselective determination of cetirizine in human plasma by normal-phase
      liquid chromatography-atmospheric pressure chemical ionization-tandem mass
      spectrometry.
AB  - A highly sensitive and enantioselective method has been developed and validated
      for the determination of levocetirizine [(R)-cetirizine] in human plasma by
      normal-phase liquid chromatography coupled to tandem mass spectrometry with an
      atmospheric pressure chemical ionization (APCI) interface in the positive ion
      mode. Enantioselective separation was achieved on a CHIRALPAK AD-H column using
      an isocratic mobile phase consisting of a mixture of n-hexane, ethyl alcohol,
      diethylamine, and acetic acid (60:40:0.1:0.1, v/v/v/v). Levocetirizine-D(8) was
      used as an internal standard (IS). Levocetirizine and the IS were detected by
      multiple-reaction monitoring (MRM). Mass transitions of analyte and IS were m/z
      389.2->201.1 and 397.2->201.1, respectively. Under optimized analytical
      conditions, a baseline separation of two enantiomers and IS was obtained in less
      than 11 min. Samples were prepared by a simple two-step extraction by protein
      precipitation using acetonitrile followed by liquid-liquid extraction with a n
      hexane-dichloromethane mixture (50:50, v/v). The standard curve for
      levocetirizine was linear (r(2)>0.995) in the concentration range 0.5-300 ng/mL.
      Recovery was between 97.0 and 102.2% at low, medium, and high concentration. The
      limit of quantification (LOQ) was 0.5 ng/mL. Other method validation parameters,
      such as precision, accuracy, and stability, were very satisfactory. Finally, the
      proposed method was successfully applied to the study of enantioselective oral
      pharmacokinetics of levocetirizine in healthy Korean volunteers.

PMID- 21081291
TI  - Determination of sodium nifurstyrenate and nitrovin residues in edible food by
      liquid chromatography-tandem mass spectrometry after ultrasound-assisted
      extraction.
AB  - A specific and sensitive method based on liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) has been developed for the determination of nitrovin and
      sodium nifurstyrenate residues in muscle and liver of swine and chicken and in
      muscle of fish. Sample preparation procedure includes ultrasound-assisted
      extraction with acetonitrile, defatting with n-hexane and final clean-up with
      solid phase extraction (SPE) on Oasis HLB cartridges. The analytes were detected
      in multiple reaction monitoring (MRM) under negative scan mode acquiring two
      diagnostic product ions for sodium nifurstyrenate and under positive mode for
      nitrovin. The averaged decision limits (CCalpha; alpha 1%) ranged 0.09-0.26
      MUg/kg while the detection capability (CCbeta; beta 5%) was 0.33-0.97 MUg/kg in
      the tissues. Reasonable recoveries (71-110%) spiked in muscle and liver showed
      excellent relative standard deviation (RSD). The validated method was simple,
      rapid, sensitive, and complied with the regulations for the determination of
      nitrovin and sodium nifurstyrenate residues in food matrices.

PMID- 21081292
TI  - Application of a liquid chromatography/tandem mass spectrometry method to
      pharmacokinetic study of mangiferin in rats.
AB  - A simple, rapid and accurate liquid chromatography-electrospray ionization-tandem
      mass spectrometry method was developed and validated for quantification of
      mangiferin in rat plasma. After the addition of the internal standard (IS)
      paracetamol, plasma samples were pretreated by protein precipitation.
      Chromatographic separation was carried out on a C(18) column by isocratic elution
      with methanol-acetonitrile-1% acetic acid (40:3:57, v/v/v). The detection was
      performed on a Sciex API 3000 LC/MS/MS with TurboIonSpray ionization (ESI) inlet
      in the positive ion MRM mode. Good linearity was achieved over the concentration
      range of 3.01-601 ng/mL. Intra- and inter-day precisions were less than 9.1%, and
      accuracy ranged from 100.5% to 104.0%. The pharmacokinetic profiles of free
      mangiferin at three dose levels and mangiferin in Zhimu decoction and Zhimu
      Huangbai decoction were studied for the first time in rats by this method. After
      single intragastric administration of free mangiferin 17.5, 35 and 70 mg/kg,
      C(max) and AUC increased but non-proportional to the doses. At the same dose
      level (35 mg/kg), C(max) and AUC of mangiferin in two decoctions were
      significantly higher than the corresponding values of free mangiferin.

PMID- 21081293
TI  - Simultaneous determination of three Panax notoginseng saponins at sub-nanograms
      by LC-MS/MS in dog plasma for pharmacokinetics of compound Danshen tablets.
AB  - Compound Danshen tablets are composed of Panax notoginseng, Salvia miltiorrhiza
      and Borneol. The tablets are prescribed for treatment of cardiovascular diseases
      in China. The present study aimed at developing a specific and sensitive LC-MS/MS
      method to simultaneously determine three bioactive P. notoginseng saponins, i.e.,
      notoginsenoside R1, ginsenoside Rg1 and Rb1, in dogs after a single oral
      administration of the compound tablets in order to obtain the clinically relevant
      saponin-related pharmacodynamics of the tablets in patients. The R1, Rg1 and Rb1
      were extracted from dog plasma with acetone-methanol (80:20, v/v), separated by
      reversed phase liquid chromatography and determined by tandem mass spectrometry
      (LC-MS/MS) with positive electrospray ionization (ESI). The developed method
      reached lower limit of quantitation (LLOQ) at 0.10 ng/ml for the three saponins.
      The method was validated in terms of selectivity, matrix effects, linearity,
      precision and accuracy, and then was applied to a pharmacokinetic study of the
      three bioactive saponins simultaneously in dogs after a single oral
      administration of compound Danshen tablets at a clinical equivalent dose. The
      C(max) and AUC((0-infinity)) for R1, Rg1 and Rb1 were 1.91, 3.34 and 28.6 ng/ml,
      and 7.5, 11.0, and 1712 (h ng/ml), respectively.

PMID- 21081299
TI  - Exposure assessment in cohort studies of childhood asthma.
AB  - BACKGROUND: The environment is suspected to play an important role in the
      development of childhood asthma. Cohort studies are a powerful observational
      design for studying exposure-response relationships, but their power depends in
      part upon the accuracy of the exposure assessment. OBJECTIVE: The purpose of this
      paper is to summarize and discuss issues that make accurate exposure assessment a
      challenge and to suggest strategies for improving exposure assessment in
      longitudinal cohort studies of childhood asthma and allergies. DATA SYNTHESIS:
      Exposures of interest need to be prioritized, because a single study cannot
      measure all potentially relevant exposures. Hypotheses need to be based on
      proposed mechanisms, critical time windows for effects, prior knowledge of
      physical, physiologic, and immunologic development, as well as genetic pathways
      potentially influenced by the exposures. Modifiable exposures are most important
      from the public health perspective. Given the interest in evaluating gene
      environment interactions, large cohort sizes are required, and planning for data
      pooling across independent studies is critical. Collection of additional samples,
      possibly through subject participation, will permit secondary analyses. Models
      combining air quality, environmental, and dose data provide exposure estimates
      across large cohorts but can still be improved. CONCLUSIONS: Exposure is best
      characterized through a combination of information sources. Improving exposure
      assessment is critical for reducing measurement error and increasing power, which
      increase confidence in characterization of children at risk, leading to improved
      health outcomes.

PMID- 21081300
TI  - Many putative endocrine disruptors inhibit prostaglandin synthesis.
AB  - BACKGROUND: Prostaglandins (PGs) play key roles in development and maintenance of
      homeostasis of the adult body. Despite these important roles, it remains unclear
      whether the PG pathway is a target for endocrine disruption. However, several
      known endocrine-disrupting compounds (EDCs) share a high degree of structural
      similarity with mild analgesics. OBJECTIVES AND METHODS: Using cell-based
      transfection and transduction experiments, mass spectrometry, and organotypic
      assays together with molecular modeling, we investigated whether inhibition of
      the PG pathway by known EDCs could be a novel point of endocrine disruption.
      RESULTS: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli
      cell line and in human primary mast cells. The EDCs also reduced PG synthesis in
      ex vivo rat testis, and this reduction was correlated with a reduced testosterone
      production. The inhibition of PG synthesis occurred without involvement of
      canonical PG receptors or the peroxisome proliferator-activated receptors
      (PPARs), which have previously been described as targets of EDCs. Instead, our
      results suggest that the compounds may bind directly into the active site of the
      cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic
      acid to PG precursors without interfering with the expression of the COX enzymes.
      A common feature of the PG inhibitory EDCs is the presence of aromatic groups
      that may stabilize binding in the hydrophobic active site of the COX enzymes.
      CONCLUSION: Our findings suggest a hitherto unknown mode of action by EDCs
      through inhibition of the PG pathway and suggest new avenues to investigate
      effects of EDCs on reproductive and immunological disorders that have become
      increasingly common in recent decades.

PMID- 21081301
TI  - Long-term exposure to traffic-related air pollution and the risk of coronary
      heart disease hospitalization and mortality.
AB  - BACKGROUND: Epidemiologic studies have demonstrated that exposure to road traffic
      is associated with adverse cardiovascular outcomes. OBJECTIVES: We aimed to
      identify specific traffic-related air pollutants that are associated with the
      risk of coronary heart disease (CHD) morbidity and mortality to support evidence
      based environmental policy making. METHODS: This population-based cohort study
      included a 5-year exposure period and a 4-year follow-up period. All residents 45
      85 years of age who resided in Metropolitan Vancouver during the exposure period
      and without known CHD at baseline were included in this study (n=452,735).
      Individual exposures to traffic-related air pollutants including black carbon,
      fine particles [aerodynamic diameter <= 2.5 um (PM(2.5))], nitrogen dioxide
      (NO(2)), and nitric oxide were estimated at residences of the subjects using land
      use regression models and integrating changes in residences during the exposure
      period. CHD hospitalizations and deaths during the follow-up period were
      identified from provincial hospitalization and death registration records.
      RESULTS: An interquartile range elevation in the average concentration of black
      carbon (0.94 * 10(-5)/m filter absorbance, equivalent to approximately 0.8
      ug/m(3) elemental carbon) was associated with a 3% increase in CHD
      hospitalization (95% confidence interval, 1-5%) and a 6% increase in CHD
      mortality (3-9%) after adjusting for age, sex, preexisting comorbidity,
      neighborhood socioeconomic status, and copollutants (PM(2.5) and NO(2)). There
      were clear linear exposure-response relationships between black carbon and
      coronary events. CONCLUSIONS: Long-term exposure to traffic-related fine
      particulate air pollution, indicated by black carbon, may partly explain the
      observed associations between exposure to road traffic and adverse cardiovascular
      outcomes.

PMID- 21081303
TI  - Serum cytokine levels as putative prognostic markers in the progression of
      chronic HCV hepatitis to cirrhosis.
AB  - Hepatitis C virus (HCV) infection can present as an acute manifestation, and can
      lead to severe complications such as chronic hepatitis, cirrhosis, and
      hepatocellular carcinoma (HCC). It represents a global health problem because
      there is no vaccine currently available. Cytokines play an important role in
      viral clearance, infection control, inflammation, regeneration and fibrosis, and
      also are implicated in the pathological processes occurring in the liver during
      viral infection. Immunological markers of chronic HCV hepatitis progression as
      compared to cirrhosis and HCC would be extremely useful, particularly for
      distinguishing between the molecules produced during HCV-induced chronic
      inflammation and those secreted during cirrhosis and HCC. In this work, we
      evaluated the serum levels of several cytokines, chemokines and growth factors in
      30 patients affected by chronic HCV (HC), 30 patients affected by HCV-related
      cirrhosis (LC) and 20 healthy, control subjects. We used a multiplex biometric
      ELISA-based immunoassay in order to identify molecules that might be useful for
      monitoring the progression of HCV to liver cirrhosis and, possibly, to cancer.
      Our results show that some pro-inflammatory molecules are significantly up
      regulated, and play a role as immunological markers in the intermediate steps
      towards liver cancer, and that hepatocyte growth factor (HGF) is a specific
      marker of liver cirrhosis. Finally, these data will be used to define a
      cytokinome profile, which might prove useful for studies involving the transition
      of chronic inflammation to neoplastic processes.

PMID- 21081304
TI  - Relationship between IL-6/ERK and NF-kappaB: a study in normal and pathological
      human prostate gland.
AB  - BACKGROUND: There is growing evidence that inflammation is a causal factor in
      cancer, where pro-inflammatory cytokines such as IL-6, IL-1 or TNF-alpha could
      induce cellular proliferation by activation of NF-kappaB. This study focuses on
      the IL-6/ERK transduction pathway, its relationship with NF-kappaB, and the
      consequences of dysregulation in the development of prostate pathologies such as
      benign prostate hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and
      prostate cancer (PC). METHODS: Immunohistochemical and Western blot analyses for
      IL-6, gp-130, Raf-1, MEK-1, ERK-1, p-MEK, ERK-2, p-ERK, NF-kappaB/p-50 and NF
      kappaB/p-65 were carried out in 20 samples of normal prostate glands, 35 samples
      of BPH, 27 samples with a diagnosis of PIN (low-grade PIN or high-grade PIN), and
      95 samples of PC (23 with low, 51 with medium and 21 with high Gleason scores).
      RESULTS: Immunoreaction to IL-6, gp-130, ERK-1, ERK-2, p-ERK and NF-kappaB/p50
      was found in the cytoplasm of epithelial cells in normal prostate samples; p-MEK
      was found in the nucleus of epithelial cells; but not expression to Raf-1, MEK-1
      and NF-kappaB/p65. In BPH, all of these proteins were immunoexpressed, while
      there was increased immunoexpression of IL-6, gp-130, p-MEK, ERK-1, ERK-2 and NF
      kappaB/p50 (cytoplasm). In PC, immunoexpression of IL-6 and gp-130 were similar
      to that found in BPH; while immunoexpression of Raf-1, MEK-1, p-MEK, ERK-1, ERK
      2, p-ERK, NF-kappaB/p50 (nucleus and cytoplasm), and NF-kappaB/p65 (nucleus and
      cytoplasm) was higher than in BPH. CONCLUSION: Translocation of NF-kappaB to the
      nucleus in PC and high-grade PIN could be stimulated by the IL-6/ERK transduction
      pathway, but might also be stimulated by other transduction pathways, such as TNF
      alpha/NIK, TNF/p38, IL-1/NIK or IL-1/p38. Activation of NF-kappaB in PC could
      regulate IL-6 expression. These transduction pathways are also related to
      activation of other transcription factors such as Elk-1, ATF-2 or c-myc (also
      involved in cell proliferation and survival). PC is a heterogeneous disease,
      where multiple transduction pathways might alter the apoptosis/proliferation
      balance. Significant attention should be give to the combination of novel agents
      directed towards inactivation of pro-inflammatory cytokines than can disrupt
      tumour cell growth.

PMID- 21081302
TI  - Developmental neurotoxicants in e-waste: an emerging health concern.
AB  - OBJECTIVE: Electronic waste (e-waste) has been an emerging environmental health
      issue in both developed and developing countries, but its current management
      practice may result in unintended developmental neurotoxicity in vulnerable
      populations. To provide updated information about the scope of the issue,
      presence of known and suspected neurotoxicants, toxicologic mechanisms, and
      current data gaps, we conducted this literature review. DATA SOURCES: We reviewed
      original articles and review papers in PubMed and Web of Science regarding e
      waste toxicants and their potential developmental neurotoxicity. We also searched
      published reports of intergovernmental and governmental agencies and
      nongovernmental organizations on e-waste production and management practice. DATA
      EXTRACTION: We focused on the potential exposure to e-waste toxicants in
      vulnerable populations-that is, pregnant women and developing children-and
      neurodevelopmental outcomes. In addition, we summarize experimental evidence of
      developmental neurotoxicity and mechanisms. DATA SYNTHESIS: In developing
      countries where most informal and primitive e-waste recycling occurs,
      environmental exposure to lead, cadmium, chromium, polybrominated diphenyl
      ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is
      prevalent at high concentrations in pregnant women and young children.
      Developmental neurotoxicity is a serious concern in these regions, but human
      studies of adverse effects and potential mechanisms are scarce. The unprecedented
      mixture of exposure to heavy metals and persistent organic pollutants warrants
      further studies and necessitates effective pollution control measures.
      CONCLUSIONS: Pregnant women and young children living close to informal e-waste
      recycling sites are at risk of possible perturbations of fetus and child
      neurodevelopment.

PMID- 21081305
TI  - Correlation between child and parental perceptions of health-related quality of
      life in epilepsy using the PedsQL.v4.0 measurement model.
AB  - Health-related quality-of-life measures in childhood epilepsy are typically
      limited to a particular functional domain, specific age group, parent proxy
      report, or child self-report. Generic health-related quality-of-life instruments
      in paediatric epilepsy comparing child self-reports with simultaneous parent
      proxy-reports have not been previously investigated. A previously validated
      generic questionnaire, the Pediatric Quality of Life version 4 (PedsQL.v4.0), was
      used to prospectively assess parental and child perceptions of health-related
      quality of life in 100 children with epilepsy. The correlation between child and
      parental health-related quality-of-life perceptions across all domains was
      excellent (p < 0.001) and both were significantly lower than those for healthy
      controls (p < 0.001). Parents' perceptions of their children's health-related
      quality of life were lower than those for other chronic illnesses (p < 0.001),
      especially for refractory epilepsy. The presence of neurological or psychiatric
      comorbidities also had an adverse impact on health-related quality of life. The
      PedsQL.v4.0 measures health-related quality of life from both the parent's and
      child's perspective. Ease of use makes this instrument attractive for routine
      clinical use.

PMID- 21081306
TI  - Retractions in the scientific literature: do authors deliberately commit research
      fraud?
AB  - BACKGROUND: Papers retracted for fraud (data fabrication or data falsification)
      may represent a deliberate effort to deceive, a motivation fundamentally
      different from papers retracted for error. It is hypothesised that fraudulent
      authors target journals with a high impact factor (IF), have other fraudulent
      publications, diffuse responsibility across many co-authors, delay retracting
      fraudulent papers and publish from countries with a weak research infrastructure.
      METHODS: All 788 English language research papers retracted from the PubMed
      database between 2000 and 2010 were evaluated. Data pertinent to each retracted
      paper were abstracted from the paper and the reasons for retraction were derived
      from the retraction notice and dichotomised as fraud or error. Data for each
      retracted article were entered in an Excel spreadsheet for analysis. RESULTS:
      Journal IF was higher for fraudulent papers (p<0.001). Roughly 53% of fraudulent
      papers were written by a first author who had written other retracted papers
      ('repeat offender'), whereas only 18% of erroneous papers were written by a
      repeat offender (chi=88.40; p<0.0001). Fraudulent papers had more authors
      (p<0.001) and were retracted more slowly than erroneous papers (p<0.005).
      Surprisingly, there was significantly more fraud than error among retracted
      papers from the USA (chi(2)=8.71; p<0.05) compared with the rest of the world.
      CONCLUSIONS: This study reports evidence consistent with the 'deliberate fraud'
      hypothesis. The results suggest that papers retracted because of data fabrication
      or falsification represent a calculated effort to deceive. It is inferred that
      such behaviour is neither naive, feckless nor inadvertent.

PMID- 21081307
TI  - Secondhand smoke exposure and the risk of hearing loss.
AB  - Hearing loss has been associated with tobacco smoking, but its relationship with
      secondhand smoke is not known. We sought to investigate the association between
      secondhand smoke exposure and hearing loss in a nationally representative sample
      of adults. The National Health and Nutrition Examination Survey (NHANES), a
      nationally representative cross-sectional dataset, was utilised to investigate
      the association between secondhand smoke exposure and hearing loss. Data
      collected from non-smoking participants aged 20-69 years were included in the
      analysis if they had completed audiometric testing, had a valid serum continue
      value, and provided complete smoking, medical co-morbidity and noise exposure
      histories (N=3307). Hearing loss was assessed from averaged pure-tone thresholds
      over low- or mid-frequencies (500, 1000 and 2000 Hz) and high-frequencies (3000,
      4000, 6000 and 8000 Hz), and was defined as mild or greater severity (pure-tone
      average in excess of 25 dB HL). Second-Hand Smoke (SHS) exposure was
      significantly associated with increased risk of hearing loss for low-/mid
      frequencies (adjusted OR=1.14; 95% CI 1.02-1.28 for never smokers and 1.30; 1.10
      1.54 for former smokers) and high-frequencies (1.40; 1.22-1.81 for former
      smokers), after controlling for potential confounders. Findings from the present
      analysis indicate that SHS exposure is associated with hearing loss in non
      smoking adults.

PMID- 21081309
TI  - Training in epidemiology and disease control for humanitarian emergencies.

PMID- 21081308
TI  - Maternal age, birth order, and race: differential effects on birthweight.
AB  - BACKGROUND: Studies examining the influence of maternal age and birth order on
      birthweight have not effectively disentangled the relative contributions of each
      factor to birthweight, especially as they may differ by race. METHODS: A
      population-based, cross-sectional study of North Carolina births from 1999 to
      2003 was performed. Analysis was restricted to 510 288 singleton births from 28
      to 42 weeks' gestation with no congenital anomalies. Multivariable linear
      regression was used to model maternal age and birth order on birthweight,
      adjusting for infant sex, education, marital status, tobacco use and race.
      RESULTS: Mean birthweight was lower for non-Hispanic black individuals (NHB, 3166
      g) compared with non-Hispanic white individuals (NHW, 3409 g) and Hispanic
      individuals (3348 g). Controlling for covariates, birthweight increased with
      maternal age until the early 30s. Race-specific modelling showed that the upper
      extremes of maternal age had a significant depressive effect on birthweight for
      NHW and NHB (35+ years, p<0.001), but only age less than 25 years was a
      significant contributor to lower birthweights for Hispanic individuals, p<0.0001.
      Among all racial subgroups, birth order had a greater influence on birthweight
      than maternal age, with the largest incremental increase from first to second
      births. Among NHB, birth order accounted for a smaller increment in birthweight
      than for NHW and Hispanic women. CONCLUSION: Birth order exerts a greater
      influence on birthweight than maternal age, with signficantly different effects
      across racial subgroups.

PMID- 21081310
TI  - The impact of 20 mph traffic speed zones on inequalities in road casualties in
      London.
AB  - BACKGROUND: Road traffic casualties show some of the widest socioeconomic
      differentials of any cause of morbidity or mortality, and as yet there is little
      evidence on what works to reduce them. This study quantified the current and
      potential future impact of the introduction of 20 mph zones on socioeconomic
      inequalities in road casualties in London. METHODS: An observational study based
      on analysis of geographically coded police road casualties data, 1987-2006.
      Changes in counts of casualties from road collisions, those killed and seriously
      injured and pedestrian injuries by quintile of deprivation were calculated.
      RESULTS: The effect of 20 mph zones was similar across quintiles of socioeconomic
      deprivation, being associated with a 41.8% (95% CI 21.0% to 62.6%) decline in
      casualties in areas in the least deprived quintile versus 38.3% (31.5% to 45.0%)
      in the most deprived quintile. Because of the greater number of road casualties
      in deprived areas and the targeting of zones to such areas, the number of
      casualties prevented by zones was substantially larger in areas of greater
      socioeconomic deprivation. However, the underlying decline in road casualties on
      all roads was appreciably greater in less deprived areas (p<0.001 for trend) so
      that despite the targeting of 20 mph zones, socioeconomic inequalities in road
      injuries in London have widened over time. Extending 20 mph schemes has only
      limited the potential to reduce differentials further. CONCLUSIONS: The
      implementation of 20 mph zones targeted at deprived areas has mitigated widening
      socioeconomic differentials in road injury in London and to some degree narrowed
      them, but there is limited potential for further gain.

PMID- 21081311
TI  - Maternal smoking during pregnancy and criminal offending among adult offspring.
AB  - BACKGROUND: Although a number of previous studies have reported an association
      between maternal smoking during pregnancy (MSP) and externalising behaviour
      problems among offspring, it has been suggested that this relationship is
      spurious due to the failure of these studies to properly account for important
      confounding factors. METHODS: The relationship between MSP and adult criminal
      offending was examined using data from 3766 members of the Providence, Rhode
      Island, cohort of the Collaborative Perinatal Project. Information on MSP and
      most potential confounders was collected prospectively throughout pregnancy. In
      1999-2000 all offspring had reached 33 years of age and an adult criminal record
      check was performed. Because previous research has been criticised for not
      properly accounting for confounding influences, our primary aim was to determine
      whether the MSP-criminal offending relationship held after efficiently adjusting
      for a wide range of sociodemographic and family background characteristics using
      propensity score methods. RESULTS: The association between MSP and adult criminal
      offending remained after controlling for propensity scores. Offspring of mothers
      who smoked heavily during pregnancy (>=20 cigarettes per day) had the greatest
      odds of an adult arrest record (OR 1.31, 95% CI 1.06 to 1.62). Findings also
      suggest that MSP may be an independent risk factor for adult criminal histories
      marked by multiple arrests. Lastly, our findings show that the impact of MSP
      operates similarly across both genders. CONCLUSION: Results from this study
      provide evidence of an association between heavy MSP and long-term criminal
      offending. Any causal association is likely to be weak to moderate in strength.

PMID- 21081312
TI  - A survey of combinatorial methods for phylogenetic networks.
AB  - The evolutionary history of a set of species is usually described by a rooted
      phylogenetic tree. Although it is generally undisputed that bifurcating
      speciation events and descent with modifications are major forces of evolution,
      there is a growing belief that reticulate events also have a role to play.
      Phylogenetic networks provide an alternative to phylogenetic trees and may be
      more suitable for data sets where evolution involves significant amounts of
      reticulate events, such as hybridization, horizontal gene transfer, or
      recombination. In this article, we give an introduction to the topic of
      phylogenetic networks, very briefly describing the fundamental concepts and
      summarizing some of the most important combinatorial methods that are available
      for their computation.

PMID- 21081313
TI  - Red algae lose key mitochondrial genes in response to becoming parasitic.
AB  - Red algal parasites are unusual because the vast majority of them parasitize
      species with which they share a recent common ancestor. This strategy has earned
      them the name "adelphoparasites," from the Greek, adelpho, meaning "kin."
      Intracellular adelphoparasites are very rare in nature, yet have independently
      evolved hundreds of times among the floridiophyte red algae. Much is known about
      the life history and infection cycle of these parasites but nearly nothing in
      known about their genomes. We sequenced the mitochondrial genomes of the free
      living Gracilariopsis andersonii and its closely related parasite Gracilariophila
      oryzoides to determine what effect a parasitic lifestyle has on the genomes of
      red algal parasites. Whereas the parasite genome is similar to the host in many
      ways, the genes encoding essential proteins ATP8 and SDHC are pseudogenes in the
      parasite. The mitochondrial genome of parasite from a different class of red
      algae, Plocamiocolax puvinata, has lost the atp8 gene entirely, indicating that
      this gene is no longer critical in red algal parasite mitochondria.

PMID- 21081314
TI  - ERAD components in organisms with complex red plastids suggest recruitment of a
      preexisting protein transport pathway for the periplastid membrane.
AB  - The plastids of cryptophytes, haptophytes, and heterokontophytes (stramenopiles)
      (together once known as chromists) are surrounded by four membranes, reflecting
      the origin of these plastids through secondary endosymbiosis. They share this
      trait with apicomplexans, which are alveolates, the plastids of which have been
      suggested to stem from the same secondary symbiotic event and therefore form a
      phylogenetic clade, the chromalveolates. The chromists are quantitatively the
      most important eukaryotic contributors to primary production in marine
      ecosystems. The mechanisms of protein import across their four plastid membranes
      are still poorly understood. Components of an endoplasmic reticulum-associated
      degradation (ERAD) machinery in cryptophytes, partially encoded by the reduced
      genome of the secondary symbiont (the nucleomorph), are implicated in protein
      transport across the second outermost plastid membrane. Here, we show that the
      haptophyte Emiliania huxleyi, like cryptophytes, stramenopiles, and
      apicomplexans, possesses a nuclear-encoded symbiont-specific ERAD machinery
      (SELMA, symbiont-specific ERAD-like machinery) in addition to the host ERAD
      system, with targeting signals that are able to direct green fluorescent protein
      or yellow fluorescent protein to the predicted cellular localization in
      transformed cells of the stramenopile Phaeodactylum tricornutum. Phylogenies of
      the duplicated ERAD factors reveal that all SELMA components trace back to a red
      algal origin. In contrast, the host copies of cryptophytes and haptophytes
      associate with the green lineage to the exclusion of stramenopiles and
      alveolates. Although all chromalveolates with four membrane-bound plastids
      possess the SELMA system, this has apparently not arisen in a single
      endosymbiotic event. Thus, our data do not support the chromalveolate hypothesis.

PMID- 21081469
TI  - NF-kappaB targets miR-16 and miR-21 in gastric cancer: involvement of
      prostaglandin E receptors.
AB  - Cigarette smoke is one of the risk factors for gastric cancer and nicotine has
      been reported to promote tumor growth. Deregulation of microRNA (miRNA) and
      cyclooxygenase-2 (COX-2) expressions are hallmarks of many cancers including
      gastric cancer. Here, we used an miRNA array platform covering a panel of 95
      human miRNAs to examine the expression profile in nicotine-treated gastric cancer
      cells. We found that miR-16 and miR-21 were upregulated upon nicotine
      stimulation, transfection with anti-miR-16 or anti-miR-21 significantly abrogated
      cell proliferation. In contrast, ectopic miR-16 or miR-21 expression exhibited a
      similar stimulatory effect on cell proliferation as nicotine. Nicotine-mediated
      IkappaBalpha degradation and nuclear factor-kappa B (NF-kappaB) translocation
      dose-dependently. Knockdown of NF-kappaB by short interfering RNA (siRNA) or
      specific inhibitor (Bay-11-7085) markedly suppressed nicotine-induced cell
      proliferation and upregulation of miR-16 and miR-21. Interestingly, NF-kappaB
      binding sites were located in both miR-16 and miR-21 gene transcriptional
      elements and we showed that nicotine enhanced the binding of NF-kappaB to the
      promoters of miR-16 and miR-21. Furthermore, activation of COX-2/prostaglandin E2
      (PGE2) signaling in response to nicotine was mediated by the action of
      prostaglandin E receptors (EP2 and EP4). EP2 or EP4 siRNA or antagonists impaired
      the nicotine-mediated NF-kappaB activity, upregulation of miR-16 and miR-21 and
      cell proliferation. Taken together, these results suggest that miR-16 and miR-21
      are directly regulated by the transcription factor NF-kappaB and yet nicotine
      promoted cell proliferation is mediated via EP2/4 receptors. Perhaps this study
      may shed light on the development of anticancer drugs to improve the
      chemosensitivity in smokers.

PMID- 21081470
TI  - Rapid induction of colon carcinogenesis in CYP1A-humanized mice by 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant
      heterocyclic amine produced during the cooking of meats and fish, is suspected to
      be a human carcinogen. Metabolic activation of PhIP is primarily mediated by the
      enzyme cytochrome P450 (CYP) 1A2. Metabolism of PhIP by CYP1A2 differs
      considerably between humans and rodents, with more N(2)-hydroxylation
      (activation) and less 4'-hydroxylation (detoxication) in humans. Transgenic CYP1A
      humanized mice (hCYP1A-mice), which have the human CYP1A1 and CYP1A2 genes but
      lack the murine orthologs Cyp1a1 and Cyp1a2, provide an excellent opportunity to
      develop a relevant model to study dietary-induced colon carcinogenesis. The
      treatment with 200 mg/kg PhIP by oral gavage, followed by 1.5% dextran sodium
      sulfate (DSS) in the drinking water for 7 days, was found to be an effective
      combination to induce colon carcinogenesis in hCYP1A-mice. Tumor multiplicity at
      week 6 was calculated to be 3.75 +/- 0.70 and for week 10 was 3.90 +/- 0.61 with
      80-95% of the tumors being adenocarcinomas. No tumors were found in the similarly
      treated wild-type mice. Western blots revealed overexpression of beta-catenin, c
      Myc, cyclin D1, inducible nitric oxide synthase and cyclooxygenase-2 in colon
      tumor samples. Strong nuclear localization of beta-catenin was observed in
      tumors. These results illustrate that PhIP and DSS combination produces rapid
      colon carcinogenesis in hCYP1A-mice and this is an effective model to mimic human
      colon carcinogenesis.

PMID- 21081471
TI  - Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk:
      findings from the Los Angeles-Shanghai bladder case-control study.
AB  - Genome-wide association studies have associated common variations at chromosomes
      5p15 and 15q25 with lung cancer risk. The 5p15 locus has also been associated
      with increased bladder cancer risk in a recent report. The 15q25 locus has been
      associated with nicotine dependence and self-reported number of cigarettes smoked
      per day in some studies and it was proposed that its association with lung cancer
      may be mediated through differences in smoking behavior. Here, we investigated
      the roles of variations at 5p15 (rs401681, rs402710, rs2736098 and rs2736100) and
      15q25 (rs1051730 and rs8034191) in bladder cancer etiology in two case-control
      studies conducted separately in Los Angeles County, CA, USA (498 cases and 588
      controls) and in Shanghai, China (506 cases and 530 controls). We replicated the
      association between the 5p15 locus and bladder cancer among non-Hispanic whites
      (NHW) in Los Angeles [for rs2736100, per C allele odds ratio (OR) = 1.23; 95%
      confidence interval (CI), 1.02-1.48; P = 0.029] and among Chinese in Shanghai (OR
      = 1.22; 95% CI, 1.02-1.47; P = 0.033). Both rs1051730 and rs8034191 at 15q25 were
      rare among Chinese. Among NHW, a significant association was found between
      rs8034191 and bladder cancer which persisted after adjustment for cigarette
      smoking status, number of cigarettes smoked per day and number of years of
      smoking (per C allele OR = 1.26; 95% CI, 1.04-1.54; P = 0.017). Our results
      support 5p15 and 15q25 as susceptibility regions for bladder cancer risk.

PMID- 21081472
TI  - MSP-induced RON activation upregulates uPAR expression and cell invasiveness via
      MAPK, AP-1 and NF-kappaB signals in gastric cancer cells.
AB  - Overexpression of recepteur d'Origine nantais (RON) and urokinase plasminogen
      activator receptor (uPAR) have been observed in human gastric cancers. However,
      the interaction between RON and uPAR in gastric cancer is unclear. The present
      study investigated the effect of macrophage-stimulating protein (MSP, the RON
      ligand) on uPAR expression and the underlying signal pathways in human gastric
      cancer AGS cells. uPAR messenger RNA expression was induced by MSP in a time- and
      concentration-dependent manner. MSP also induced uPAR promoter activity. The
      introduction of RON-specific small interfering RNA (siRNA) significantly affected
      the MSP-induced uPAR transcription. Deleted and site-directed mutagenesis studies
      demonstrated the involvement of the binding sites of transcription factor nuclear
      factor-kappaB (NF-kappaB) and activator protein (AP)-1 in the MSP-induced uPAR
      expression. Studies with expression vectors encoding mutated-type NF-kappaB
      signaling molecules and AP-1 decoy confirmed that NF-kappaB and AP-1 were
      essential for the MSP-induced uPAR expression. In addition, MSP induced the
      activation of extracellular signal-regulated kinase-1/2 (Erk-1/2), c-Jun amino
      terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Dominant
      negative mutants (K97M and TAM67) and specific inhibitors of Erk-1/2 and JNK were
      able to suppress the MSP-induced uPAR expression. AGS cells pretreated with MSP
      showed a remarkably enhanced invasiveness, which was partially abrogated by siRNA
      targeted RON and uPAR-neutralizing antibodies. The above results suggest that MSP
      induces uPAR expression via MAPK, AP-1 and NF-kappaB signaling pathways and, in
      turn, stimulates cell invasiveness in human gastric cancer AGS cells.

PMID- 21081473
TI  - Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and
      heterocyclic amines in relation to risk of colorectal neoplasia.
AB  - Animal work implicates chemical carcinogens, such as polycyclic aromatic
      hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) as contributing to
      the development of colorectal cancer (CRC). The epidemiologic evidence, however,
      remains inconsistent possibly due to intra-individual variation in bioactivation
      of these compounds. We conducted a case-control study of colorectal adenoma (914
      cases, 1185 controls) and CRC (496 cases, 607 controls) among Japanese Americans,
      European Americans and Native Hawaiians to investigate the association of genetic
      variation in the PAH and HAA bioactivation pathway (CYP1A1, CYP1A2, CYP1B1, AHR
      and ARNT) identified through sequencing with risk of colorectal neoplasia, as
      well as their interactions with smoking and intakes of red meat and HAAs. The A
      allele for ARNT rs12410394 was significantly inversely associated with CRC [odds
      ratios (ORs) and 95% confidence intervals (CIs) for GG, AG and AA genotypes:
      1.00, 0.66 (0.48-0.89), 0.54 (0.37-0.78), P(trend) = 0.0008] after multiple
      comparison adjustment. CYP1A2 rs11072508 was marginally significantly associated
      with CRC, where each copy of the T allele was associated with reduced risk (OR:
      0.72, 95% CI: 0.58-0.88, P(trend) = 0.0017). No heterogeneity of genetic effects
      across racial/ethnic groups was detected. In addition, no significant interaction
      was observed after adjusting for multiple testing between genetic variants and
      pack-years of smoking, intake of red meat or HAAs (PhIP, MeIQx, Di-MeIQx or total
      HAAs) or NAT2 genotype (Rapid versus Slow or Intermediate). This study suggests
      that the genomic region around ARNT rs12410394 may harbor variants associated
      with CRC.

PMID- 21081474
TI  - 2-Tellurium-bridged beta-cyclodextrin, a thioredoxin reductase inhibitor,
      sensitizes human breast cancer cells to TRAIL-induced apoptosis through DR5
      induction and NF-kappaB suppression.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent
      antitumor activity via membrane receptors on cancer cells without deleterious
      side effects for normal tissue. Unfortunately, breast cancer cells, as many other
      cancer types, develop resistance to TRAIL; therefore, TRAIL sensitizing agents
      are currently being explored. 2-Tellurium-bridged beta-cyclodextrin (2-TeCD) is a
      synthetic organotellurium compound, with both glutathione peroxidase-like
      catalytic ability and thioredoxin reductase inhibitor activity. In the present
      study, we reported that 2-TeCD sensitized TRAIL-resistant human breast cancer
      cells and xenograft tumors to undergo apoptosis. In vitro, 2-TeCD efficiently
      sensitized MDA-MB-468 and T47D cells, but not untransformed human mammary
      epithelial cells, to TRAIL-mediated apoptosis, as evidenced by enhanced caspase
      activity and poly (adenosine diphosphate-ribose) polymerase cleavage. From a
      mechanistic standpoint, we showed that 2-TeCD treatment of breast cancer cells
      significantly upregulated the messenger RNA and protein levels of TRAIL receptor,
      death receptor (DR) 5, in a transcription factor Sp1-dependent manner. 2-TeCD
      treatment also suppressed TRAIL-induced nuclear factor-kappaB (NF-kappaB)
      prosurvival pathways by preventing cytosolic IkappaBalpha degradation, as well as
      p65 nuclear translocation. Consequently, the combined administration suppressed
      anti-apoptotic molecules that are transcriptionally regulated by NF-kappaB. In
      vivo, 2-TeCD and TRAIL were well tolerated in mice and their combination
      significantly inhibited growth of MDA-MB-468 xenografts and promoted apoptosis.
      Upregulation of DR5 and downregulation of NF-kappaB by the dual treatment were
      also observed in tumor tissues. Overall, 2-TeCD sensitizes resistant breast
      cancer cells to TRAIL-based apoptosis in vitro and in vivo. These findings
      provide strong evidence for the therapeutic potential of this combination against
      breast cancers.

PMID- 21081475
TI  - MicroRNA in colorectal cancer: from benchtop to bedside.
AB  - Colon carcinogenesis represents a stepwise progression from benign polyps to
      invasive adenocarcinomas and distant metastasis. It is believed that these
      pathologic changes are contributed by aberrant activation or inactivation of
      protein-coding proto-oncogenes and tumor suppressor genes. However, recent
      discoveries in microRNA (miRNA) research have reshaped our understanding of the
      role of non-protein-coding genes in carcinogenesis. In this regard, a remarkable
      number of miRNAs exhibit differential expression in colon cancer tissues. These
      miRNAs alter cell proliferation, apoptosis and metastasis through their
      interactions with intracellular signaling networks. From a clinical perspective,
      polymorphisms within miRNA-binding sites are associated with the risk for colon
      cancer, whereas miRNAs isolated from feces or blood may serve as biomarkers for
      early diagnosis. Altered expression of miRNA or polymorphisms in miRNA-related
      genes have also been shown to correlate with patient survival or treatment
      outcome. With further insights into miRNA dysregulation in colon cancer and the
      advancement of RNA delivery technology, it is anticipated that novel miRNA-based
      therapeutics will emerge.

PMID- 21081476
TI  - Detailed analysis of DNA repair and senescence marker kinetics over the life span
      of a human fibroblast cell line.
AB  - We examined phosphorylation of H2AX, a marker for DNA double-strand breaks over
      the life of a human fibroblast cell line. This marker was compared with a number
      of other cellular senescence and DNA repair endpoints. An increase in gammaH2AX
      foci number was observed after 24 hours of repair time following DNA damage over
      the course of fibroblast passaging. Progressive and relatively constant changes
      in growth retardation, doubling time, and telomere length were also observed. The
      fraction of cells expressing beta-gal, a marker of cellular senescence, increased
      considerably around the 40th passage as did some other cell morphology endpoints.
      The detectable gammaH2AX foci at 24 hours after ionizing radiation were far fewer
      than the number detected at 1 hour across all passage numbers. We conclude that
      although residual DNA damage level increases with passage number, it is unlikely
      to be the result of less efficient DNA repair in the aged fibroblast since most
      DNA damage is repaired, even at late passages.

PMID- 21081477
TI  - Defective adaption of erythrocytes during acute hypoxia injury in an elderly
      population.
AB  - The present study investigated the changes in several erythrocyte oxidative
      stress biomarkers in hypoxic elderly individuals to analyze the deleterious
      effects of low oxyhemoglobin saturation in an elderly population. We collected
      blood samples from one normoxic middle-aged group and two groups composed of
      individuals older than 75 years of age: one normoxic group and one hypoxic group.
      Aging appeared to provoke a defective erythrocyte antioxidant defense associated
      with increased oxidative damage in the elderly population. Acute hypoxia
      activated an insufficient antioxidant defense response as suggested by the
      oxidative damage observed. The oxidative imbalance presented in older
      participants and increased in hypoxia participants had a direct effect on
      glyceraldehyde-3-phosphate dehydrogenase cell distribution. Oxidative stress
      levels altered Band 3 protein and mediated caspase-3 activation in erythrocyte
      from the aged group although it was not extended to hypoxic individuals.
      Therefore, aged participants appeared to activate an insufficient antioxidant
      response against hypoxia-related oxidative stress.

PMID- 21081478
TI  - Multiple pathways regulating the calorie restriction response in yeast.
AB  - In yeast, SIR2 overexpression or calorie restriction (CR) results in life-span
      extension. It was previously suggested that CR activates Sir2 by reducing the
      levels of Sir2 inhibitors, NADH, or nicotinamide. Whereas NADH reduction is
      associated with an increase in respiration, nicotinamide clearance is induced by
      the upregulation of PNC1. Here, we show that, consistent with the hormesis
      hypothesis, PNC1 is part of a transcriptional stress response module consisting
      of 39 genes that increases under various stresses. Under high CR (0.1% glucose),
      Pnc1 becomes activated and its levels increase. However, low CR (0.5% glucose)
      increases yeast life span without PNC1 induction or activation of any
      transcriptional stress response. Instead, microarray analysis of low CR shows
      that the messenger RNA levels of iron transport genes increase, suggesting that
      this mode of CR is regulated by a shift toward respiration and lowering NADH
      levels. Thus, at least two pathways regulate the CR response in yeast.

PMID- 21081479
TI  - Ancient vertebrate conserved noncoding elements have been evolving rapidly in
      teleost fishes.
AB  - Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that
      often function as tissue-specific enhancers. In this study, we have identified
      CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish,
      stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate,
      as the base genome and investigated the evolution of these ancient vertebrate
      CNEs (aCNEs) in bony vertebrate lineages. Our analysis shows that aCNEs have been
      evolving at different rates in different bony vertebrate lineages. Although 78
      83% of CNEs have diverged beyond recognition ("lost") in different teleost
      fishes, only 24% and 40% have been lost in the chicken and mammalian lineages,
      respectively. Relative rate tests of substitution rates in CNEs revealed that the
      teleost fish CNEs have been evolving at a significantly higher rate than those in
      other bony vertebrates. In the ray-finned fish lineage, 68% of aCNEs were lost
      before the divergence of the four teleosts. This implicates the "fish-specific"
      whole-genome duplication in the accelerated evolution and the loss of a large
      number of both copies of duplicated CNEs in teleost fishes. The aCNEs are rich in
      tissue-specific enhancers and thus many of them are likely to be evolutionarily
      constrained cis-regulatory elements. The rapid evolution of aCNEs might have
      affected the expression patterns driven by them. Transgenic zebrafish assay of
      some human CNE enhancers that have been lost in teleosts has indicated instances
      of conservation or changes in trans-acting factors between mammals and fishes.

PMID- 21081482
TI  - Two stationary nonhomogeneous Markov models of nucleotide sequence evolution.
AB  - The general Markov model (GMM) of nucleotide substitution does not assume the
      evolutionary process to be stationary, reversible, or homogeneous. The GMM can be
      simplified by assuming the evolutionary process to be stationary. A stationary
      GMM is appropriate for analyses of phylogenetic data sets that are
      compositionally homogeneous; a data set is considered to be compositionally
      homogeneous if a statistical test does not detect significant differences in the
      marginal distributions of the sequences. Though the general time-reversible (GTR)
      model assumes stationarity, it also assumes reversibility and homogeneity. We
      propose two new stationary and nonhomogeneous models--one constrains the GMM to
      be reversible, whereas the other does not. The two models, coupled with the GTR
      model, comprise a set of nested models that can be used to test the assumptions
      of reversibility and homogeneity for stationary processes. The two models are
      extended to incorporate invariable sites and used to analyze a seven-taxon
      hominoid data set that displays compositional homogeneity. We show that within
      the class of stationary models, a nonhomogeneous model fits the hominoid data
      better than the GTR model. We note that if one considers a wider set of models
      that are not constrained to be stationary, then an even better fit can be
      obtained for the hominoid data. However, the methods for reducing model
      complexity from an extremely large set of nonstationary models are yet to be
      developed.

PMID- 21081481
TI  - Quantifying the impact of dependent evolution among sites in phylogenetic
      inference.
AB  - Nearly all commonly used methods of phylogenetic inference assume that characters
      in an alignment evolve independently of one another. This assumption is
      attractive for simplicity and computational tractability but is not biologically
      reasonable for RNAs and proteins that have secondary and tertiary structures.
      Here, we simulate RNA and protein-coding DNA sequence data under a general model
      of dependence in order to assess the robustness of traditional methods of
      phylogenetic inference to violation of the assumption of independence among
      sites. We find that the accuracy of independence-assuming methods is reduced by
      the dependence among sites; for proteins this reduction is relatively mild, but
      for RNA this reduction may be substantial. We introduce the concept of effective
      sequence length and its utility for considering information content in
      phylogenetics.

PMID- 21081480
TI  - Ancestral and derived protein import pathways in the mitochondrion of
      Reclinomonas americana.
AB  - The evolution of mitochondria from ancestral bacteria required that new protein
      transport machinery be established. Recent controversy over the evolution of
      these new molecular machines hinges on the degree to which ancestral bacterial
      transporters contributed during the establishment of the new protein import
      pathway. Reclinomonas americana is a unicellular eukaryote with the most gene
      rich mitochondrial genome known, and the large collection of membrane proteins
      encoded on the mitochondrial genome of R. americana includes a bacterial-type
      SecY protein transporter. Analysis of expressed sequence tags shows R. americana
      also has components of a mitochondrial protein translocase or "translocase in the
      inner mitochondrial membrane complex." Along with several other membrane proteins
      encoded on the mitochondrial genome Cox11, an assembly factor for cytochrome c
      oxidase retains sequence features suggesting that it is assembled by the SecY
      complex in R. americana. Despite this, protein import studies show that the
      RaCox11 protein is suited for import into mitochondria and functional
      complementation if the gene is transferred into the nucleus of yeast.
      Reclinomonas americana provides direct evidence that bacterial protein transport
      pathways were retained, alongside the evolving mitochondrial protein import
      machinery, shedding new light on the process of mitochondrial evolution.

PMID- 21081483
TI  - Who are the peer educators? HIV prevention in South African schools.
AB  - Characteristics of learners who become peer educators are rarely explored despite
      the potential relevance to the success of peer education programmes. Fifteen high
      schools selected to implement peer education HIV prevention programmes in South
      Africa were recruited. A total of 2339 Grade 10 learners were surveyed and
      comparisons were made between socio-demographic characteristics, key skills,
      school experience and sexual behaviour of those students who had volunteered or
      been chosen by teachers to be peer educators (n = 295) and their fellow students
      (n = 2044), the potential recipients of the programme. On most of the socio
      demographic variables, school experiences, aspirations, sexual debut and use of
      condoms at last sex or whether they had been tested for HIV status, there were no
      significant differences between the two groups. Volunteers and teacher-chosen
      peer educators tended to be younger than their classmates (16.19 versus 16.52, P
      < 0.0001), score higher on a goal-orientation scale (3.27 versus 3.15, P =<
      0.0001) and had more access to basic resources [electricity (97.9% versus 94.0%,
      P = 0.006), a bicycle (41.9% versus 32.7%, P = 0.004) or car (50.2% versus 41.0%,
      P = 0.005)]. Further research is needed to explore specific peer educator
      characteristics and recruitment and selection approaches that are associated with
      effective HIV prevention interventions.

PMID- 21081484
TI  - Diagnosing lung cancer earlier in the UK.

PMID- 21081485
TI  - Gender differences in COPD: are women more susceptible to smoking effects than
      men?

PMID- 21081486
TI  - Pulmonary dirofilariasis in a Caucasian patient with metastasised osteosarcoma in
      a non-endemic European region.

PMID- 21081487
TI  - Distinct roles of Ape1 protein in the repair of DNA damage induced by ionizing
      radiation or bleomycin.
AB  - Ionizing radiation (IR) and bleomycin (BLM) are used to treat various types of
      cancers. Both agents generate cytotoxic double strand breaks (DSB) and abasic
      (apurinic/apyrimidinic (AP)) sites in DNA. The human AP endonuclease Ape1 acts on
      abasic or 3'-blocking DNA lesions such as those generated by IR or BLM. We
      examined the effect of siRNA-mediated Ape1 suppression on DNA repair and cellular
      resistance to IR or BLM in human B-lymphoblastoid TK6 cells and HCT116 colon
      tumor cells. Partial Ape1 deficiency (~30% of normal levels) sensitized cells
      more dramatically to BLM than to IR cytotoxicity. In both cases, expression of
      the unrelated yeast AP endonuclease, Apn1, largely restored resistance. Ape1
      deficiency increased DNA AP site accumulation due to IR treatment but reduced the
      number of DSB. In contrast, for BLM, there were more DSB under Ape1 deficiency,
      with little change in the accumulation of AP sites. Although the role of Ape1 in
      generating DSB was greater for IR, the enzyme facilitated removal of AP sites,
      which may mitigate the cytotoxic effects of IR. In contrast, BLM generates
      scattered AP sites, and the DSB have 3'-phosphoglycolate termini that require
      Ape1 processing. These DSB persist under Ape1 deficiency. Apoptosis induced by
      BLM (but not by IR) under Ape1 deficiency was partially p53-dependent, more
      dramatically in TK6 than HCT116 cells. Thus, Ape1 suppression or inhibition may
      be a more efficacious adjuvant for BLM than for IR cancer therapy, particularly
      for tumors with a functional p53 pathway.

PMID- 21081488
TI  - Biochemical characterization of bacteriophage T4 Mre11-Rad50 complex.
AB  - The Mre11-Rad50 complex (MR) from bacteriophage T4 (gp46/47) is involved in the
      processing of DNA double-strand breaks. Here, we describe the activities of the
      T4 MR complex and its modulation by proteins involved in homologous
      recombination. T4 Mre11 is a Rad50- and Mn(2+)-dependent dsDNA exonuclease and
      ssDNA endonuclease. ATP hydrolysis is required for the removal of multiple
      nucleotides via dsDNA exonuclease activity but not for the removal of the first
      nucleotide or for ssDNA endonuclease activity, indicating ATP hydrolysis is only
      required for repetitive nucleotide removal. By itself, Rad50 is a relatively
      inefficient ATPase, but the presence of Mre11 and dsDNA increases ATP hydrolysis
      by 20-fold. The ATP hydrolysis reaction exhibits positive cooperativity with Hill
      coefficients ranging from 1.4 for Rad50 alone to 2.4 for the Rad50-Mre11-DNA
      complex. Kinetic assays suggest that approximately four nucleotides are removed
      per ATP hydrolyzed. Directionality assays indicate that the prevailing activity
      is a 3' to 5' dsDNA exonuclease, which is incompatible with the proposed role of
      MR in the production of 3' ssDNA ends. Interestingly, we found that in the
      presence of a recombination mediator protein (UvsY) and ssDNA-binding protein
      (gp32), Mre11 is capable of using Mg(2+) as a cofactor for its nuclease activity.
      Additionally, the Mg(2+)-dependent nuclease activity, activated by UvsY and gp32,
      results in the formation of endonuclease reaction products. These results suggest
      that gp32 and UvsY may alter divalent cation preference and facilitate the
      formation of a 3' ssDNA overhang, which is a necessary intermediate for
      recombination-mediated double-strand break repair.

PMID- 21081489
TI  - miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic
      response of endothelial cells.
AB  - The miR-200 family plays a crucial role in epithelial to mesenchymal transition
      via controlling cell migration and polarity. We hypothesized that miR-200b, one
      miR-200 family member, could regulate angiogenic responses via modulating
      endothelial cell migration. Delivery of the miR-200b mimic in human microvascular
      endothelial cells (HMECs) suppressed the angiogenic response, whereas miR-200b
      depleted HMECs exhibited elevated angiogenesis in vitro, as evidenced by
      Matrigel(r) tube formation and cell migration. Using in silico studies, miR
      target reporter assay, and Western blot analysis revealed that v-ets
      erythroblastosis virus E26 oncogene homolog 1 (Ets-1), a crucial angiogenesis
      related transcription factor, serves as a novel direct target of miR-200b.
      Knocking down endogenous Ets-1 simulated an anti-angiogenic response of the miR
      200b mimic-transfected cells. Certain Ets-1-associated genes, namely matrix
      metalloproteinase 1 and vascular endothelial growth factor receptor 2, were
      negatively regulated by miR-200b. Overexpression of Ets-1 rescued miR-200b
      dependent impairment in angiogenic response and suppression of Ets-1-associated
      gene expression. Both hypoxia as well as HIF-1alpha stabilization inhibited miR
      200b expression and elevated Ets-1 expression. Experiments to identify how miR
      200b modulates angiogenesis under a low oxygen environment illustrated that
      hypoxia-induced miR-200b down-regulation de-repressed Ets-1 expression to promote
      angiogenesis. This study provides the first evidence that hypoxia-sensitive miR
      200b is involved in induction of angiogenesis via directly targeting Ets-1 in
      HMECs.

PMID- 21081490
TI  - Possible roles of exceptionally conserved residues around the selectivity filters
      of sodium and calcium channels.
AB  - In the absence of x-ray structures of sodium and calcium channels their homology
      models are used to rationalize experimental data and design new experiments. A
      challenge is to model the outer-pore region that folds differently from potassium
      channels. Here we report a new model of the outer-pore region of the NaV1.4
      channel, which suggests roles of highly conserved residues around the selectivity
      filter. The model takes from our previous study (Tikhonov, D. B., and Zhorov, B.
      S. (2005) Biophys. J. 88, 184-197) the general disposition of the P-helices,
      selectivity filter residues, and the outer carboxylates, but proposes new intra-
      and inter-domain contacts that support structural stability of the outer pore.
      Glycine residues downstream from the selectivity filter are proposed to
      participate in knob-into-hole contacts with the P-helices and S6s. These contacts
      explain the adapted tetrodotoxin resistance of snakes that feed on toxic prey
      through valine substitution of isoleucine in the P-helix of repeat IV. Polar
      residues five positions upstream from the selectivity filter residues form H
      bonds with the ascending-limb backbones. Exceptionally conserved tryptophans are
      engaged in inter-repeat H-bonds to form a ring whose pi-electrons would
      facilitate passage of ions from the outer carboxylates to the selectivity filter.
      The outer-pore model of CaV1.2 derived from the NaV1.4 model is also stabilized
      by the ring of exceptionally conservative tryptophans and H-bonds between the P
      helices and ascending limbs. In this model, the exceptionally conserved aspartate
      downstream from the selectivity-filter glutamate in repeat II facilitates passage
      of calcium ions to the selectivity-filter ring through the tryptophan ring.
      Available experimental data are discussed in view of the models.

PMID- 21081491
TI  - Tamm-Horsfall glycoprotein interacts with renal outer medullary potassium channel
      ROMK2 and regulates its function.
AB  - Tamm-Horsfall glycoprotein (THGP) or Uromodulin is a membrane protein exclusively
      expressed along the thick ascending limb (TAL) and early distal convoluted tubule
      (DCT) of the nephron. Mutations in the THGP encoding gene result in Familial
      Juvenile Hyperuricemic Nephropathy (FJHN), Medullary Cystic Kidney Disease type 2
      (MCKD-2), and Glomerulocystic Kidney Disease (GCKD). The physicochemical and
      biological properties of THGP have been studied extensively, but its
      physiological function in the TAL remains obscure. We performed yeast two-hybrid
      screening employing a human kidney cDNA library and identified THGP as a
      potential interaction partner of the renal outer medullary potassium channel
      (ROMK2), a key player in the process of salt reabsorption along the TAL.
      Functional analysis by electrophysiological techniques in Xenopus oocytes showed
      a strong increase in ROMK current amplitudes when co-expressed with THGP. The
      effect of THGP was specific for ROMK2 and did not influence current amplitudes
      upon co-expression with Kir2.x, inward rectifier potassium channels related to
      ROMK. Single channel conductance and open probability of ROMK2 were not altered
      by co-expression of THGP, which instead increased surface expression of ROMK2 as
      determined by patch clamp analysis and luminometric surface quantification,
      respectively. Despite preserved interaction with ROMK2, disease-causing THGP
      mutants failed to increase its current amplitude and surface expression. THGP(-/
      ) mice exhibited increased ROMK accumulation in intracellular vesicular
      compartments when compared with WT animals. Therefore, THGP modulation of ROMK
      function confers a new role of THGP on renal ion transport and may contribute to
      salt wasting observed in FJHN/MCKD-2/GCKD patients.

PMID- 21081493
TI  - PARP-14 functions as a transcriptional switch for Stat6-dependent gene
      activation.
AB  - A subset of poly ADP-ribose polymerases (PARP) that also contain macro domains
      regulate transcription. One such macro PARP, PARP-14 alters interleukin 4 (IL-4)
      and Stat6-dependent transcription. Stat6, activated by IL-4 plays an important
      role in T helper cell immunity and B cell responses. Here we define the mechanism
      by which PARP-14 regulates Stat6-activated transcription. Under non-stimulating
      conditions, PARP-14 recruits HDAC 2 and 3 to IL-4 responsive promoters. In the
      presence of IL-4, PARP-14 promotes efficient binding of Stat6 to its target
      genes. Moreover, HDAC 2 and 3 are released from the promoter with an IL-4 signal,
      this is aided by the ADP-ribosylation of the HDACs by PARP-14. The HDACs and PARP
      14 get replaced by coactivators containing HAT activity. Based on these
      observations we put forth a mechanism in which PARP-14 functions as a
      transcriptional switch for Stat6-dependent gene induction. Thus, in the absence
      of a signal PARP-14 acts as a transcriptional repressor by recruiting HDACs. In
      contrast, in the presence of IL-4 the catalytic activity of PARP-14 facilitates
      Stat6 binding to the promoter, and release of HDACs so as to activate
      transcription.

PMID- 21081492
TI  - Phosphorylation of phosphatidate phosphatase regulates its membrane association
      and physiological functions in Saccharomyces cerevisiae: identification of
      SER(602), THR(723), AND SER(744) as the sites phosphorylated by CDC28 (CDK1)
      encoded cyclin-dependent kinase.
AB  - The Saccharomyces cerevisiae PAH1-encoded phosphatidate phosphatase (PAP)
      catalyzes the penultimate step in the synthesis of triacylglycerol and plays a
      role in the transcriptional regulation of phospholipid synthesis genes. PAP is
      phosphorylated at multiple Ser and Thr residues and is dephosphorylated for in
      vivo function by the Nem1p-Spo7p protein phosphatase complex localized in the
      nuclear/endoplasmic reticulum membrane. In this work, we characterized seven
      previously identified phosphorylation sites of PAP that are within the Ser/Thr
      Pro motif. When expressed on a low copy plasmid, wild type PAP could not
      complement the pah1Delta mutant in the absence of the Nem1p-Spo7p complex.
      However, phosphorylation-deficient PAP (PAP-7A) containing alanine substitutions
      for the seven phosphorylation sites bypassed the requirement of the phosphatase
      complex and complemented the pah1Delta nem1Delta mutant phenotypes, such as
      temperature sensitivity, nuclear/endoplasmic reticulum membrane expansion,
      decreased triacylglycerol synthesis, and derepression of INO1 expression.
      Subcellular fractionation coupled with immunoblot analysis showed that PAP-7A was
      highly enriched in the membrane fraction. In fluorescence spectroscopy analysis,
      the PAP-7A showed tighter association with phospholipid vesicles than wild type
      PAP. Using site-directed mutagenesis of PAP, we identified Ser(602), Thr(723),
      and Ser(744), which belong to the seven phosphorylation sites, as the sites
      phosphorylated by the CDC28 (CDK1)-encoded cyclin-dependent kinase. Compared with
      the dephosphorylation mimic of the seven phosphorylation sites, alanine
      substitution for Ser(602), Thr(723), and/or Ser(744) had a partial effect on
      circumventing the requirement for the Nem1p-Spo7p complex.

PMID- 21081494
TI  - AKR1B7 is induced by the farnesoid X receptor and metabolizes bile acids.
AB  - Although bile acids are crucial for the absorption of lipophilic nutrients in the
      intestine, they are cytotoxic at high concentrations and can cause liver damage
      and promote colorectal carcinogenesis. The farnesoid X receptor (FXR), which is
      activated by bile acids and abundantly expressed in enterohepatic tissues, plays
      a crucial role in maintaining bile acids at safe concentrations. Here, we show
      that FXR induces expression of Akr1b7 (aldo-keto reductase 1b7) in murine small
      intestine, colon, and liver by binding directly to a response element in the
      Akr1b7 promoter. We further show that AKR1B7 metabolizes 3-keto bile acids to
      3beta-hydroxy bile acids that are less toxic to cultured cells than their 3alpha
      hydroxy precursors. These findings reveal a feed-forward, protective pathway
      operative in murine enterohepatic tissues wherein FXR induces AKR1B7 to detoxify
      bile acids.

PMID- 21081495
TI  - c-Abl phosphorylation of Mdm2 facilitates Mdm2-Mdmx complex formation.
AB  - Mdm2 and Mdmx are oncoproteins that have essential yet nonredundant roles in
      development and function as part of a multicomponent ubiquitinating complex that
      targets p53 for proteasomal degradation. However, in response to DNA damage, Mdm2
      and Mdmx are phosphorylated and protect p53 through various mechanisms. It has
      been predicted that Mdm2-Mdmx complex formation modulates Mdm2 ligase activity,
      yet the mechanism that promotes formation of Mdm2-Mdmx complexes is unknown.
      Here, we show that optimal Mdm2-Mdmx complex formation requires c-Abl
      phosphorylation of Mdm2 both in vitro and in vivo. In addition, Abl
      phosphorylation of Mdm2 is required for efficient ubiquitination of Mdmx in
      vitro, and eliminating c-Abl signaling, using c-Abl(-/-) knock-out murine
      embryonic fibroblasts, led to a decrease in Mdmx ubiquitination. Further, p53
      levels are not induced as efficiently in c-Abl(-/-) murine embryonic fibroblasts
      following DNA damage. Overall, these results define a direct link between
      genotoxic stress-activated c-Abl kinase signaling and Mdm2-Mdmx complex
      formation. Our results add an important regulatory mechanism for the activation
      of p53 in response to DNA damage.

PMID- 21081496
TI  - Multiple scaffolding functions of {beta}-arrestins in the degradation of G
      protein-coupled receptor kinase 2.
AB  - G protein-coupled receptor kinase 2 (GRK2) plays a fundamental role in the
      regulation of G protein-coupled receptors (GPCRs), and changes in GRK2 expression
      levels can have an important impact on cell functions. GRK2 is known to be
      degraded by the proteasome pathway. We have shown previously that beta-arrestins
      participate in enhanced kinase turnover upon GPCR stimulation by facilitating
      GRK2 phosphorylation by c-Src or by MAPK or by recruiting the Mdm2 E3 ubiquitin
      ligase to the receptor complex. In this report, we have investigated how such
      diverse beta-arrestin scaffold functions are integrated to modulate GRK2
      degradation. Interestingly, we found that in the absence of GPCR activation, beta
      arrestins do not perform an adaptor role for GRK2/Mdm2 association, but rather
      compete with GRK2 for direct Mdm2 binding to regulate basal kinase turnover. Upon
      agonist stimulation, beta-arrestins-mediated phosphorylation of GRK2 at serine
      670 by MAPK facilitates Mdm2-mediated GRK2 degradation, whereas c-Src-dependent
      phosphorylation would support the action of an undetermined beta-arrestin
      recruited ligase in the absence of GPCR activation. The ability of beta-arrestins
      to play different scaffold functions would allow coordination of both Mdm2
      dependent and -independent processes aimed at the specific modulation of GRK2
      turnover in different signaling contexts.

PMID- 21081497
TI  - Tests of integrin transmembrane domain homo-oligomerization during integrin
      ligand binding and signaling.
AB  - Integrin transmembrane (TM) and/or cytoplasmic domains play a critical role in
      integrin bidirectional signaling. Although it has been shown that TM and/or
      cytoplasmic alpha and beta domains associate in the resting state and separation
      of these domains is required for both inside-out and outside-in signaling, the
      role of TM homomeric association remains elusive. Formation of TM homo-oligomers
      was observed in micelles and bacterial membranes previously, and it has been
      proposed that homomeric association is important for integrin activation and
      clustering. This study addresses whether integrin TM domains form homo-oligomers
      in mammalian cell membranes using cysteine scanning mutagenesis. Our results show
      that TM homomeric interaction does not occur before or after soluble ligand
      binding or during inside-out activation. In addition, even though the cysteine
      mutants and the heterodimeric disulfide-bounded mutant could form clusters after
      adhering to immobilized ligand, the integrin TM domains do not form homo
      oligomers, suggesting that integrin TM homomeric association is not critical for
      integrin clustering or outside-in signaling. Therefore, integrin TM homo
      oligomerization is not required for integrin activation, ligand binding, or
      signaling.

PMID- 21081498
TI  - Molybdopterin dinucleotide biosynthesis in Escherichia coli: identification of
      amino acid residues of molybdopterin dinucleotide transferases that determine
      specificity for binding of guanine or cytosine nucleotides.
AB  - The molybdenum cofactor is modified by the addition of GMP or CMP to the C4'
      phosphate of molybdopterin forming the molybdopterin guanine dinucleotide or
      molybdopterin cytosine dinucleotide cofactor, respectively. The two reactions are
      catalyzed by specific enzymes as follows: the GTP:molybdopterin
      guanylyltransferase MobA and the CTP:molybdopterin cytidylyltransferase MocA.
      Both enzymes show 22% amino acid sequence identity and are specific for their
      respective nucleotides. Crystal structure analysis of MobA revealed two conserved
      motifs in the N-terminal domain of the protein involved in binding of the guanine
      base. Based on these motifs, we performed site-directed mutagenesis studies to
      exchange the amino acids to the sequence found in the paralogue MocA. Using a
      fully defined in vitro system, we showed that the exchange of five amino acids
      was enough to obtain activity with both GTP and CTP in either MocA or MobA.
      Exchange of the complete N-terminal domain of each protein resulted in the total
      inversion of nucleotide specificity activity, showing that the N-terminal domain
      determines nucleotide recognition and binding. Analysis of protein-protein
      interactions showed that the C-terminal domain of either MocA or MobA determines
      the specific binding to the respective acceptor protein.

PMID- 21081499
TI  - The yeast homolog of heme oxygenase-1 affords cellular antioxidant protection via
      the transcriptional regulation of known antioxidant genes.
AB  - Heme oxygenase-1 (HO-1) degrades heme and protects cells from oxidative
      challenge. This antioxidant activity is thought to result from the HO-1 enzymatic
      activity, manifested by a decrease in the concentration of the pro-oxidant
      substrate heme, and an increase in the antioxidant product bilirubin. Using a
      global transcriptional approach, and yeast as a model, we show that HO-1 affords
      cellular protection via up-regulation of transcripts encoding enzymes involved in
      cellular antioxidant defense, rather than via its oxygenase activity. Like
      mammalian cells, yeast responds to oxidative stress by expressing its HO-1
      homolog and, compared with the wild type, heme oxygenase-null mutant cells have
      increased sensitivity toward oxidants that is rescued by overexpression of human
      HO-1 or its yeast homolog. Increased oxidant sensitivity of heme oxygenase-null
      mutant cells is explained by a decrease in the expression of the genes encoding
      gamma-glutamylcysteine synthetase, glutathione peroxidase, catalase, and
      methionine sulfoxide reductase, because overexpression of any of these genes
      affords partial, and overexpression of all four genes provides complete,
      protection to the null mutant. Genes encoding antioxidant enzymes represent only
      a small portion of the 480 differentially expressed transcripts in heme oxygenase
      null mutants. Transcriptional regulation may be explained by the nuclear
      localization of heme oxygenase observed in oxidant-challenged cells. Our results
      challenge the notion that HO-1 functions simply as a catabolic and antioxidant
      enzyme. They indicate much broader functions for HO-1, the unraveling of which
      may help explain the multiple biological responses reported in animals as a
      result of altered HO-1 expression.

PMID- 21081500
TI  - Peroxisome proliferator-activated receptor {alpha} is responsible for the up
      regulation of hepatic glucose-6-phosphatase gene expression in fasting and db/db
      Mice.
AB  - Glucose-6-phosphatase (G6Pase) is a key enzyme that is responsible for the
      production of glucose in the liver during fasting or in type 2 diabetes mellitus
      (T2DM). During fasting or in T2DM, peroxisome proliferator-activated receptor
      alpha (PPARalpha) is activated, which may contribute to increased hepatic glucose
      output. However, the mechanism by which PPARalpha up-regulates hepatic G6Pase
      gene expression in these states is not well understood. We evaluated the
      mechanism by which PPARalpha up-regulates hepatic G6Pase gene expression in
      fasting and T2DM states. In PPARalpha-null mice, both hepatic G6Pase and
      phosphoenolpyruvate carboxykinase levels were not increased in the fasting state.
      Moreover, treatment of primary cultured hepatocytes with Wy14,643 or fenofibrate
      increased the G6Pase mRNA level. In addition, we have localized and characterized
      a PPAR-responsive element in the promoter region of the G6Pase gene. Chromatin
      immunoprecipitation (ChIP) assay revealed that PPARalpha binding to the putative
      PPAR-responsive element of the G6Pase promoter was increased in fasted wild-type
      mice and db/db mice. These results indicate that PPARalpha is responsible for
      glucose production through the up-regulation of hepatic G6Pase gene expression
      during fasting or T2DM animal models.

PMID- 21081501
TI  - The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the
      amyloid precursor protein.
AB  - The amyloid precursor protein (APP) is cleaved by beta- and gamma-secretases to
      generate the beta-amyloid (Abeta) peptides, which are present in large amounts in
      the amyloid plaques of Alzheimer disease (AD) patient brains. Non-amyloidogenic
      processing of APP by alpha-secretases leads to proteolytic cleavage within the
      Abeta peptide sequence and shedding of the soluble APP ectodomain (sAPPalpha),
      which has been reported to be endowed with neuroprotective properties. In this
      work, we have shown that activation of the purinergic receptor P2X7 (P2X7R)
      stimulates sAPPalpha release from mouse neuroblastoma cells expressing human APP,
      from human neuroblastoma cells and from mouse primary astrocytes or neural
      progenitor cells. sAPPalpha shedding is inhibited by P2X7R antagonists or
      knockdown of P2X7R with specific small interfering RNA (siRNA) and is not
      observed in neural cells from P2X7R-deficient mice. P2X7R-dependent APP-cleavage
      is independent of extracellular calcium and strongly inhibited by hydroxamate
      based metalloprotease inhibitors, TAPI-2 and GM6001. However, knockdown of a
      disintegrin and metalloproteinase-9 (ADAM9), ADAM10 and ADAM17 by specific siRNA,
      known to have alpha-secretase activity, does not block the P2X7R-dependent non
      amyloidogenic pathway. Using several specific pharmacological inhibitors, we
      demonstrate that the mitogen-activated protein kinase modules Erk1/2 and JNK are
      involved in P2X7R-dependent alpha-secretase activity. Our study suggests that
      P2X7R, which is expressed in hippocampal neurons and glial cells, is a potential
      therapeutic target in AD.

PMID- 21081502
TI  - Neuroprotection by minocycline caused by direct and specific scavenging of
      peroxynitrite.
AB  - Minocycline prevents oxidative protein modifications and damage in disease models
      associated with inflammatory glial activation and oxidative stress. Although the
      drug has been assumed to act by preventing the up-regulation of proinflammatory
      enzymes, we probed here its direct chemical interaction with reactive oxygen
      species. The antibiotic did not react with superoxide or (*)NO radicals, but
      peroxynitrite (PON) was scavenged in the range of ~1 MUm minocycline and below.
      The interaction of pharmacologically relevant minocycline concentrations with PON
      was corroborated in several assay systems and significantly exceeded the efficacy
      of other antibiotics. Minocycline was degraded during the reaction with PON, and
      the resultant products lacked antioxidant properties. The antioxidant activity of
      minocycline extended to cellular systems, because it prevented neuronal
      mitochondrial DNA damage and glutathione depletion. Maintenance of neuronal
      viability under PON stress was shown to be solely dependent on direct chemical
      scavenging by minocycline. We chose alpha-synuclein (ASYN), known from
      Parkinsonian pathology as a biologically relevant target in chemical and cellular
      nitration reactions. Submicromolar concentrations of minocycline prevented
      tyrosine nitration of ASYN by PON. Mass spectrometric analysis revealed that
      minocycline impeded nitrations more effectively than methionine oxidations and
      dimerizations of ASYN, which are secondary reactions under PON stress. Thus, PON
      scavenging at low concentrations is a novel feature of minocycline and may help
      to explain its pharmacological activity.

PMID- 21081503
TI  - RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes
      with pICln for binding and modulates PRMT5 complex composition and substrate
      specificity.
AB  - Protein arginine methylation plays a critical role in differential gene
      expression through modulating protein-protein and protein-DNA/RNA interactions.
      Although numerous proteins undergo arginine methylation, only limited information
      is available on how protein arginine methyltransferases (PRMTs) identify their
      substrates. The human PRMT5 complex consists of PRMT5, WD45/MEP50 (WD repeat
      domain 45/methylosome protein 50), and pICln and catalyzes the symmetrical
      arginine dimethylation of its substrate proteins. pICln recruits the spliceosomal
      Sm proteins to the PRMT5 complex for methylation, which allows their subsequent
      loading onto snRNA to form small nuclear ribonucleoproteins. To understand how
      the PRMT5 complex is regulated, we investigated its biochemical composition and
      identified RioK1 as a novel, stoichiometric component of the PRMT5 complex. We
      show that RioK1 and pICln bind to PRMT5 in a mutually exclusive fashion. This
      results in a PRMT5-WD45/MEP50 core structure that either associates with pICln or
      RioK1 in distinct complexes. Furthermore, we show that RioK1 functions in analogy
      to pICln as an adapter protein by recruiting the RNA-binding protein nucleolin to
      the PRMT5 complex for its symmetrical methylation. The exclusive interaction of
      PRMT5 with either pICln or RioK1 thus provides the first mechanistic insight into
      how a methyltransferase can distinguish between its substrate proteins.

PMID- 21081506
TI  - Associations of the Emergency Severity Index triage categories with patients'
      vital signs at triage: a prospective observational study.
AB  - STUDY OBJECTIVE: Previous studies on the construct validity of the Emergency
      Severity Index (ESI) were focused on outcome measures which could not be obtained
      directly at triage. A study was conducted to the construct validity of the ESI by
      measuring the association between the ESI triage categories and patients' vital
      signs at triage. METHODS: A prospective observational study was conducted at an
      emergency department (ED) in the Netherlands. All patients who entered the ED
      between 20 July 2009 and 21 August 2009 were eligible for inclusion in the study.
      Patients' vital signs, triage category, age, gender, referrer and main complaint
      were registered. Vital signs were scored according to the Worthing Physiological
      Scoring System (WPSS) and the numerical pain rating scale. The data were analysed
      using ordinal logistic regression analyses. RESULTS: An association was found
      between ESI triage categories and patients' vital signs at triage. Patients in
      WPSS categories 'urgent' and 'alert' were more likely triaged into the urgent
      triage categories (ESI triage categories 1 and 2) than patients with normal WPSS
      scores. However, no associations were found between pain scores and ESI triage
      categories. CONCLUSION: This study supports the validity of the ESI as it showed
      that patients' vital signs are associated with the ESI triage categories.
      However, a revision of the ESI guidelines concerning pain assessments is
      necessary.

PMID- 21081504
TI  - ChChd3, an inner mitochondrial membrane protein, is essential for maintaining
      crista integrity and mitochondrial function.
AB  - The mitochondrial inner membrane (IM) serves as the site for ATP production by
      hosting the oxidative phosphorylation complex machinery most notably on the
      crista membranes. Disruption of the crista structure has been implicated in a
      variety of cardiovascular and neurodegenerative diseases. Here, we characterize
      ChChd3, a previously identified PKA substrate of unknown function (Schauble, S.,
      King, C. C., Darshi, M., Koller, A., Shah, K., and Taylor, S. S. (2007) J. Biol.
      Chem. 282, 14952-14959), and show that it is essential for maintaining crista
      integrity and mitochondrial function. In the mitochondria, ChChd3 is a peripheral
      protein of the IM facing the intermembrane space. RNAi knockdown of ChChd3 in
      HeLa cells resulted in fragmented mitochondria, reduced OPA1 protein levels and
      impaired fusion, and clustering of the mitochondria around the nucleus along with
      reduced growth rate. Both the oxygen consumption and glycolytic rates were
      severely restricted. Ultrastructural analysis of these cells revealed aberrant
      mitochondrial IM structures with fragmented and tubular cristae or loss of
      cristae, and reduced crista membrane. Additionally, the crista junction opening
      diameter was reduced to 50% suggesting remodeling of cristae in the absence of
      ChChd3. Analysis of the ChChd3-binding proteins revealed that ChChd3 interacts
      with the IM proteins mitofilin and OPA1, which regulate crista morphology, and
      the outer membrane protein Sam50, which regulates import and assembly of beta
      barrel proteins on the outer membrane. Knockdown of ChChd3 led to almost complete
      loss of both mitofilin and Sam50 proteins and alterations in several
      mitochondrial proteins, suggesting that ChChd3 is a scaffolding protein that
      stabilizes protein complexes involved in maintaining crista architecture and
      protein import and is thus essential for maintaining mitochondrial structure and
      function.

PMID- 21081505
TI  - Mycobacterial ubiquitin-like protein ligase PafA follows a two-step reaction
      pathway with a phosphorylated pup intermediate.
AB  - In Mycobacterium tuberculosis, the enzyme PafA is responsible for the activation
      and conjugation of the proteasome-targeting molecule Pup to protein substrates.
      As the proteasomal pathway has been shown to be vital to the persistence of M.
      tuberculosis, understanding the reaction mechanism of PafA is critical to the
      design of antituberculous agents. In this study, we have developed novel
      techniques to study the activity of PafA and have characterized fundamental
      features of the reaction mechanism. We show that PafA catalyzes a two-step
      reaction mechanism proceeding through a gamma-glutamyl phosphate-mixed anhydride
      intermediate that is formed on the C-terminal glutamate of Pup before transfer of
      Pup to the substrate acceptor lysine. SDS-PAGE analysis of formation of the
      phosphorylated intermediate revealed that the rate of Pup activation matched the
      maximal steady-state rate of product formation in the overall reaction and
      suggested that Pup activation was rate-limiting when all substrates were present
      at saturating concentrations. Following activation, both ADP and the
      phosphorylated intermediate remained associated with the enzyme awaiting
      nucleophilic attack by a lysine residue of the target protein. The PafA reaction
      mechanism appeared to be noticeably biased toward the stable activation of Pup in
      the absence of additional substrate and required very low concentrations of ATP
      and Pup relative to other carboxylate-amine/ammonia ligase family members. The
      bona fide nucleophilic substrate PanB showed a 3 orders of magnitude stronger
      affinity than free lysine, promoting Pup conjugation to occur close to the rate
      limit of activation with physiologically relevant concentrations of substrate.

PMID- 21081507
TI  - Human bile salt-dependent lipase efficiency on medium-chain acyl-containing
      substrates: control by sodium taurocholate.
AB  - Bile salt-dependent lipase was purified to homogeneity from lyophilized human
      milk and used to screen the influence of the acyl chain length (2-16 carbon
      atoms) on the kinetic constants k(cat) and K(m) of the hydrolysis of para
      nitrophenyl (pnp) ester substrates in the presence or absence of sodium
      taurocholate (NaTC: 0.02-20 mM). The highest k(cat) value (~3,500 s(-1)) was
      obtained with pnpC(8) as substrate, whereas the lowest K(m) (<10 uM) was that
      recorded with pnpC(10). In the absence of NaTC, the maximal catalytic efficiency
      (k(cat)/K(m)) was obtained with pnpC(8), while in the presence of NaTC
      k(cat)/K(m) was maximal with pnpC(8), pnpC(10) or pnpC(12). The bile salt
      activated the enzyme in two successive saturation phases occurring at a
      micromolar and a millimolar concentration range, respectively. The present data
      emphasize the suitability of this enzyme for the hydrolysis of medium-chain acyl
      containing substrates and throw additional light on how BSDL is activated by
      NaTC.

PMID- 21081508
TI  - Universal phosphatase-coupled glycosyltransferase assay.
AB  - A nonradioactive glycosyltransferase assay is described here. This method takes
      advantage of specific phosphatases that can be added into glycosyltransferase
      reactions to quantitatively release inorganic phosphate from the leaving groups
      of glycosyltransferase reactions. The released phosphate group is then detected
      using colorimetric malachite-based reagents. Because the amount of phosphate
      released is directly proportional to the sugar molecule transferred in a
      glycosyltransferase reaction, this method can be used to obtain accurate kinetic
      parameters of the glycosyltransferase. The assay can be performed in multiwell
      plates and quantitated by a plate reader, thus making it amenable to high
      throughput screening. It has been successfully applied to all
      glycosyltransferases available to us, including glucosyltransferases, N
      acetylglucosaminyltransferases, N-acetylgalactosyltransferases,
      galactosyltransferases, fucosyltransferases and sialyltransferases. As examples,
      we first assayed Clostridium difficile toxin B, a protein O-glucosyltransferase
      that specifically monoglucosylates and inactivates Rho family small GTPases; we
      then showed that human KTELC1, a homolog of Rumi from Drosophila, was able to
      hydrolyze UDP-Glc; and finally, we measured the kinetic parameters of human
      sialyltransferase ST6GAL1.

PMID- 21081509
TI  - Control-free calling of copy number alterations in deep-sequencing data using GC
      content normalization.
AB  - SUMMARY: We present a tool for control-free copy number alteration (CNA)
      detection using deep-sequencing data, particularly useful for cancer studies. The
      tool deals with two frequent problems in the analysis of cancer deep-sequencing
      data: absence of control sample and possible polyploidy of cancer cells. FREEC
      (control-FREE Copy number caller) automatically normalizes and segments copy
      number profiles (CNPs) and calls CNAs. If ploidy is known, FREEC assigns absolute
      copy number to each predicted CNA. To normalize raw CNPs, the user can provide a
      control dataset if available; otherwise GC content is used. We demonstrate that
      for Illumina single-end, mate-pair or paired-end sequencing, GC-contentr
      normalization provides smooth profiles that can be further segmented and analyzed
      in order to predict CNAs. AVAILABILITY: Source code and sample data are available
      at http://bioinfo-out.curie.fr/projects/freec/.

PMID- 21081510
TI  - iMAT: an integrative metabolic analysis tool.
AB  - SUMMARY: iMAT is an Integrative Metabolic Analysis Tool, enabling the integration
      of transcriptomic and proteomic data with genome-scale metabolic network models
      to predict enzymes' metabolic flux, based on the method previously described by
      Shlomi et al. The prediction of metabolic fluxes based on high-throughput
      molecular data sources could help to advance our understanding of cellular
      metabolism, since current experimental approaches are limited to measuring fluxes
      through merely a few dozen enzymes. AVAILABILITY AND IMPLEMENTATION:
      http://imat.cs.tau.ac.il/.

PMID- 21081511
TI  - GimmeMotifs: a de novo motif prediction pipeline for ChIP-sequencing experiments.
AB  - SUMMARY: Accurate prediction of transcription factor binding motifs that are
      enriched in a collection of sequences remains a computational challenge. Here we
      report on GimmeMotifs, a pipeline that incorporates an ensemble of computational
      tools to predict motifs de novo from ChIP-sequencing (ChIP-seq) data. Similar
      redundant motifs are compared using the weighted information content (WIC)
      similarity score and clustered using an iterative procedure. A comprehensive
      output report is generated with several different evaluation metrics to compare
      and evaluate the results. Benchmarks show that the method performs well on human
      and mouse ChIP-seq datasets. GimmeMotifs consists of a suite of command-line
      scripts that can be easily implemented in a ChIP-seq analysis pipeline.
      AVAILABILITY: GimmeMotifs is implemented in Python and runs on Linux. The source
      code is freely available for download at
      http://www.ncmls.eu/bioinfo/gimmemotifs/. CONTACT: s.vanheeringen@ncmls.ru.nl
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21081512
TI  - Improving the use of self-generated identification codes.
AB  - In panel studies on sensitive topics, respondent-generated identification codes
      are often used to link records across surveys. However, usually a substantial
      number of cases are lost due to the codes. These losses may cause biased
      estimates. Using more components and linking the codes by the Levenshtein string
      distance function will reduce the losses. In a simulation study and two field
      experiments, the proposed procedure outperforms the methods previously applied.

PMID- 21081513
TI  - Exposure to temporary employment and job insecurity: a longitudinal study of the
      health effects.
AB  - OBJECTIVE: This study analysed interactions between job insecurity and temporary
      employment and health. We tested the violation hypothesis (whether permanent
      employment increases the health risk associated with job insecurity) and the
      intensification hypothesis (whether temporary employment increases the health
      risk associated with job insecurity) in a longitudinal setting. Previous research
      on this topic is scarce and based on cross-sectional data. METHODS: A population
      cohort (n=1071) was surveyed at age 30 and age 42. Exposure to temporary
      employment during this 12-year period was elicited with a job-time matrix and
      measured as the score of 6-month periods. Exposure to job insecurity was measured
      according to the perceived threat of unemployment. Health at follow-up was
      assessed as optimal versus suboptimal self-rated health, sleep quality and mental
      health. In addition to sociodemographics and baseline health, the analyses were
      adjusted for exposure to unemployment, non-employment and self-employment during
      the 12-year period. RESULTS: 26% of participants had been exposed to temporary
      employment. The effect of job insecurity on health was the same in the exposed
      and unexposed groups, that is the violation hypothesis was not supported. Non
      significant interactions between the exposures and all health outcomes also
      indicated null findings regarding the intensification hypothesis. CONCLUSIONS:
      These findings suggest that perceived job insecurity can lead to adverse health
      effects in both permanent and temporary employees. Policies should aim to improve
      work-related well-being by reducing job insecurity. Efforts towards 'flexicurity'
      are important, but it is equally important to remember that a significant
      proportion of employees with a permanent contract experience job insecurity.

PMID- 21081514
TI  - Expression of CTGF and Cyr61 in colorectal cancer.
AB  - BACKGROUND: The CCN genes encode secreted extracellular matrix proteins cysteine
      rich-61 (Cyr61), connective tissue growth factor (CTGF) and nephroblastoma
      overexpressed (Nov). They are involved in diverse cellular functions. Expression
      of these factors in tumours has produced conflicting results. More recently,
      research has focused on molecular biomarkers to indicate progression of a disease
      or the susceptibility of the disease to a given treatment. AIMS: The purpose of
      this study was to determine the expression of CTGF and Cyr61 genes and proteins
      in colorectal cancer. Expression was compared with various clinicopathological
      parameters including Dukes' stage and TNM stage. We determined the in vitro
      effects of hypoxia on Cyr61 and CTGF expression in colorectal cancer cell lines.
      RESULTS: Hypoxia significantly reduced CTGF mRNA expression (p<0.01) in HT29 and
      Caco-2 cell lines. Cyr61 was induced (p<0.01) in HT29 cell lines but
      significantly reduced (p<0.01) in Caco-2 cell lines under hypoxic conditions.
      High levels of CTGF and Cyr61 mRNA were found in colorectal cancer compared with
      normal colon (p<0.05). Expression was reduced in more advanced cancers (Dukes' C
      vs Dukes' A and B). There was a significant association between CTGF protein
      expression and advancing Dukes' stage (p<0.01), T stage (p<0.01) and lymph-node
      involvement (p<0.05), but there was no significant association between Cyr61
      expression and clinicopathological parameters. CONCLUSION: Upregulation of Cyr61
      and CTGF gene expression in colorectal cancer suggests they have a role in tumour
      initiation or development. However, the genes are not as highly expressed in
      advanced stages of colorectal cancer, suggesting their role may be important at
      an early stage of tumour development. These genes maybe used as early biomarkers
      to risk-stratify patients. Hypoxia alters the expression of these genes in
      colorectal cancer cell lines. Further studies are needed to determine whether
      targeting these genes would be useful in future therapy.

PMID- 21081515
TI  - High-density tissue microarrays from prostate needle biopsies.
AB  - BACKGROUND: Formalin-fixed prostate biopsies are frequently the only tissue
      collected at the time of prostate cancer diagnosis. There is therefore a
      requirement for techniques that allow the use of these prostate biopsy specimens
      in a high-throughput analysis of immunohistochemical and fluorescence-in-situ
      hybridisation-detected biomarkers. METHODS: The authors have previously described
      methods that allow tissue microarray (TMA) construction from prostate biopsies.
      Here, we describe significant technical innovations that provide an easier and
      more robust system of biopsy-TMA construction. RESULTS AND DISCUSSION: The TMAs
      produced are of a high density (up to 104 cores each, 8 * 13) and allow a
      multiplex analysis of biomarkers in the context of clinical trials.

PMID- 21081516
TI  - Assessment of the total effective dose of miners in the underground Rozna Uranium
      Mine in the Czech Republic during the period 2004-2009.
AB  - The paper discusses the situation in the Czech Republic regarding past and
      present uranium mining activities with emphasis on the evaluation of the exposure
      of underground miners in the Rozna Uranium Mine, which is currently the only
      active mine in the country and practically in the entire European Union. The
      total effective dose has been summarised taking into account all three major
      components, namely radon short-lived decay products, long-lived alpha emitters in
      ore dust and penetrating external gamma radiation. The average and maximum values
      of the effective dose as well as the collective effective dose of underground
      miners are also presented. The purpose of the paper is to document the miners'
      exposures during a period of 6 years in a uranium mine where conditions including
      the ore grade and methods of mining showed recently some changes that may affect
      the individual components of the total effective dose.

PMID- 21081517
TI  - Comparison of the radiation dose in a cardiac IVR X-ray system.
AB  - In this study, the entrance surface dose rates received by a phantom during
      cineangiography and fluoroscopy were compared. The X-ray conditions used in the
      measurements were those normally used in facilities performing percutaneous
      coronary intervention. Although, today, the entrance surface doses
      (cineangiography and fluoroscopy) of X-ray equipment used for cardiac
      interventional radiology (IVR) tends to be lower than they were previously, some
      equipment produces a high radiation dose. Therefore, the X-ray equipment used for
      cardiac IVR procedures must be maintained in good repair and must be carefully
      calibrated. In addition, periodic measurement of the radiation dose from the X
      ray equipment used for both cineangiography and fluoroscopy for cardiac IVR is
      necessary. If the radiation dose of the X-ray system in use is too high, the IVR
      staff should determine the reason and make an effort to reduce it. Hence, the IVR
      staff must be adequately trained in radiation protection.

PMID- 21081518
TI  - Natural and artificial radioactivity distribution in soil of Fars Province, Iran.
AB  - Fars province is a large populated large province located in the southwest of
      Iran. This work presents a study of natural and radioactivity levels in soil
      samples of this province. For this purpose, 126 samples were gathered from
      different regions of the province and analysed by gamma spectroscopy to quantify
      radioactivity concentrations of radionuclides using a high-purity germanium
      detector and spectroscopy system. The results of this investigation show the
      average concentrations of 271 +/- 28 Bq kg(-1), 6.37 +/- 0.5 Bq kg(-1), 14.9 +/-
      0.9 Bq kg(-1) and 26.3 +/- 1.9 Bq kg(-1) for (40)K, (137)Cs, (232)Th and (238)U
      in soil, respectively. Finally, baseline maps were established for the
      concentrations of each of the radionuclides in different regions. The absorbed
      dose rate and the annual effective dose (AED) were also calculated for the
      radionuclides according to the guidelines of UNSCEAR 2000. The average AED from
      the radioactivity content of soil in this province was found to be 39.9 +/- 1.8
      MUSv.

PMID- 21081519
TI  - Quality assurance programme implemented in the Whole Body Monitoring Laboratory
      of IFIN-HH Romania.
AB  - The Whole Body Monitoring Laboratory (WBML) of IFIN-HH, Bucharest, Romania, is
      since the year 2000, notified and was, for the first time, notified and nominated
      as a National Individual Dosimetry Body by the competent Romanian authority in
      the field, the National Commission for Nuclear Activities Control (CNCAN), in
      accordance with the WBML-specific quality assurance programme. It respects the
      national and international legislation in force, in the nuclear, radioprotection
      and quality assurance fields, implementing them for the internal dosimetry
      activity in the WBML.

PMID- 21081520
TI  - Evaluation of the performance of two LiF:Mg,Ti and LiF:Mg,Cu,P dosemeters for
      extremity monitoring.
AB  - In this paper, the results aimed at assessing the performance of two varieties of
      LiF detectors (LiF:Mg,Ti and LiF:Mg,Cu,P) in photon fields relatively to
      reproducibility, detection threshold and angular dependence as defined in the ISO
      12794 standard are presented. The fading properties and the limit of detection
      were also investigated for both materials. The results suggest that both LiF
      varieties are well suited for extremity monitoring. However, better fading
      properties of LiF:Mg,Cu,P when compared with LiF:Mg,Ti, combined with previous
      results relatively to energy dependence suggests that LiF:Mg,Cu,P dosemeters are
      better suited for extremity monitoring.

PMID- 21081521
TI  - Routine individual monitoring of aircraft crew exposure; Czech experience and
      results 1998-2008.
AB  - Individual monitoring of aircrew of airline operators registered in the Czech
      Republic has been performed since 1998. In this work, annual effective doses and
      annual collective effective doses of aircrew from occupational exposure in the
      period from 1998 to 2008 are presented, methods used for their evaluation and
      verification are described, and general trends observed in the data are
      discussed. Annual effective doses were calculated using the computer code CARI
      from flight schedules provided by airline operators and typical flight profiles.
      The method was verified via a comparison with (i) measurements using different
      types of detectors and (ii) calculations using the CARI and EPCARD codes with
      actual flight data. It was found that average annual effective doses in the
      period from 1998 to 2008 were in the range from 1.2 to 2.0 mSv and followed the
      trend of the solar cycle. Annual collective effective doses increased from 1.4
      manSv in 1998 to 4.1 manSv in 2008 as the number of aircrew increased from 857 to
      2158 during this period. Combined relative uncertainties (coverage factor ) of
      reported individual and collective effective doses were ~ 25 %, which is well
      within the range given by the factor of 1.5. More work is needed to achieve a
      higher accuracy of this estimate.

PMID- 21081522
TI  - Individual monitoring of internal exposure for nuclear medicine workers in
      Switzerland.
AB  - Monitoring of internal exposure for nuclear medicine workers requires frequent
      measurements due to the short physical half-lives of most radionuclides used in
      this field. The aim of this study was to develop screening measurements performed
      at the workplace by local staff using standard laboratory instrumentation, to
      detect whether potential intake has occurred. Such measurements do not enable to
      determine the committed effective dose, but are adequate to verify that a given
      threshold is not exceeded. For radioiodine, i.e. (123)I, (124)I, (125)I and
      (131)I, a calibrated surface contamination monitor is placed in front of the
      thyroid to detect whether the activity threshold has been exceeded. For
      radionuclides with very short physical half-lives (<= 6 h), such as (99m)Tc and
      those used in positron emission tomography imaging, i.e. (11)C, (15)O, (18)F and
      (68)Ga, screening procedures consist in performing daily measurements of the
      ambient dose rate in front of the abdomen. Other gamma emitters used for imaging,
      i.e. (67)Ga, (111)In and (201)Tl, are measured with a scintillation detector
      located in front of the thorax. For pure beta emitters, i.e. (90)Y and (169)Er,
      as well as beta emitters with low-intensity gamma rays, i.e. (153)Sm, (177)Lu,
      (186)Re and (188)Re, the procedure consists in measuring hand contamination
      immediately after use. In Switzerland, screening procedures have been adopted by
      most nuclear medicine services since such measurements enable an acceptable
      monitoring while taking into account practical and economic considerations.

PMID- 21081523
TI  - Preliminary criteria for the very early diagnosis of systemic sclerosis: results
      of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group.
AB  - OBJECTIVE: To identify a core set of preliminary items considered as important
      for the very early diagnosis of systemic sclerosis (SSc). METHODS: A list of
      items provided by European League Against Rheumatism (EULAR) Scleroderma Trial
      and Research(EUSTAR) centres were subjected to a Delphi exercise among 110
      experts in the field of SSc. In round 1, experts were asked to choose the items
      they considered as the most important for the very early diagnosis of SSc. In
      round 2, experts were asked to reconsider the items accepted after the first
      stage. In round 3, the clinical relevance of selected items and their importance
      as measures that would lead to an early referral process were rated using
      appropriateness scores. RESULTS: Physicians from 85 EUSTAR centres participated
      in the study and provided an initial list of 121 items. After three Delphi
      rounds, the steering committee, with input from external experts, collapsed the
      121 items into three domains containing seven items, developed as follows: skin
      domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular
      domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern)
      and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I
      antibodies). Finally, the whole assembly of EUSTAR centres ratified with a
      majority vote the results in a final face-to-face meeting. CONCLUSION: The three
      Delphi rounds allowed us to identify the items considered by experts as necessary
      for the very early diagnosis of SSc. The validation of these items to establish
      diagnostic criteria is currently ongoing in a prospective observational cohort.

PMID- 21081524
TI  - Increased vascular penetration and nerve growth in the meniscus: a potential
      source of pain in osteoarthritis.
AB  - OBJECTIVES: Meniscal damage is a recognised feature of knee osteoarthritis (OA),
      although its clinical relevance remains uncertain. This study describes vascular
      penetration and nerve growth in human menisci, providing a potential mechanism
      for the genesis of pain in knee OA. METHODS: Menisci obtained post mortem were
      screened on the basis of high or low macroscopic tibiofemoral chondropathy as a
      measure of the presence and degree of OA. Forty cases (20 per group) were
      selected for the study of meniscal vascularity, and 16 (eight per group) for the
      study of meniscal innervation. Antibodies directed against alpha-actin and
      calcitonin gene-related peptide (CGRP) were used to localise blood vessels and
      nerves by histochemistry. Image analysis was used to compare vascular and nerve
      densities between groups. Data are presented as median (IQR). RESULTS: Menisci
      from knees with high chondropathy displayed degeneration of collagen bundles in
      their outer regions, which were more vascular than the inner regions, with an
      abrupt decrease in vascularity at the fibrocartilage junction. Vascular densities
      were increased in menisci from the high compared with low chondropathy group both
      in the synovium (3.8% (IQR 2.6-5.2), 2.0% (IQR 1.4-2.9), p=0.002) and at the
      fibrocartilage junction (2.3% (IQR 1.7-3.1), 1.1% (IQR 0.8-1.9), p=0.003), with a
      greater density of perivascular sensory nerve profiles in the outer region (high
      chondropathy group, 144 nerve profiles/mm(2) (IQR 134-189); low chondropathy
      group, 119 nerve profiles/mm(2) (IQR 104-144), p=0.049). CONCLUSION: Tibiofemoral
      chondropathy is associated with altered matrix structure, increased vascular
      penetration, and increased sensory nerve densities in the medial meniscus. The
      authors suggest therefore that angiogenesis and associated sensory nerve growth
      in menisci may contribute to pain in knee OA.

PMID- 21081525
TI  - Generalisability of clinical registers used for drug safety and comparative
      effectiveness research: coverage of the Swedish Biologics Register.
AB  - OBJECTIVE: To determine coverage and generalisability of data in the Swedish
      Biologics Register ARTIS. METHODS: Patients with adult onset rheumatoid arthritis
      (RA) were identified in the National Patient Register and the Swedish
      Rheumatology Quality Register, including the ARTIS cohort of patients exposed to
      biological agents. Exposure to etanercept and adalimumab between 2006 and 2008
      was determined by register linkage to the Prescribed Drug Register which contains
      patient-level data on >99% of all etanercept and adalimumab use in Sweden.
      RESULTS: Of 62 897 patients with RA, 6510 had received treatment with etanercept
      or adalimumab according to the Prescribed Drug Register. Of these, 5673 were also
      registered in ARTIS, resulting in a national coverage of 87%. The regional
      variation was small with >85% coverage in 18 of 21 counties. In multivariable
      analysis, ARTIS-registered and non-registered patients did not differ by age
      (p=0.62), sex (p=0.84) or education level (p=0.24). CONCLUSION: Nationwide drug
      dispensing and demographic data may function as quality metrics for coverage and
      generalisability assessments. Using such data, the coverage of ARTIS was
      estimated at 87% with no indications of compromised external generalisability
      regarding demography.

PMID- 21081526
TI  - Involvement of functional autoantibodies against vascular receptors in systemic
      sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc) features autoimmunity, vasculopathy and
      tissue fibrosis. The renin-angiotensin and endothelin systems have been
      implicated in vasculopathy and fibrosis. A role for autoantibody-mediated
      receptor stimulation is hypothesised, linking three major pathophysiological
      features consistent with SSc. METHODS: Serum samples from 478 patients with SSc
      (298 in the study cohort and 180 from two further independent cohorts), 372
      healthy subjects and 311 control-disease subjects were tested for antibodies
      against angiotensin II type 1 receptor (AT(1)R) and endothelin-1 type A receptor
      (ET(A)R) by solid phase assay. Binding specificities were tested by
      immunoprecipitation. The biological effects of autoantibodies in microvascular
      endothelial cells in vitro were also determined, as well as the quantitative
      differences in autoantibody levels on specific organ involvements and their
      predictive value for SSc-related mortality. RESULTS: Anti-AT(1)R and anti-ET(A)R
      autoantibodies were detected in most patients with SSc. Autoantibodies
      specifically bound to respective receptors on endothelial cells. Higher levels of
      both autoantibodies were associated with more severe disease manifestations and
      predicted SSc-related mortality. Both autoantibodies exert biological effects as
      they induced extracellular signal-regulated kinase 1/2 phosphorylation and
      increased transforming growth factor beta gene expression in endothelial cells
      which could be blocked with specific receptor antagonists. CONCLUSIONS:
      Functional autoimmunity directed at AT(1)R and ET(A)R is common in patients with
      SSc. AT(1)R and ET(A)R autoantibodies could contribute to disease pathogenesis
      and may serve as biomarkers for risk assessment of disease progression.

PMID- 21081527
TI  - Increased cartilage turnover and circulating autoantibodies in different subsets
      before the clinical onset of rheumatoid arthritis.
AB  - BACKGROUND: Previous studies have indicated that autoantibodies may be detected
      years before the clinical onset of rheumatoid arthritis (RA). Cartilage
      biomarkers, such as cartilage oligomeric matrix protein (COMP), have not been
      studied previously in samples collected before the diagnosis of RA. METHODS:
      Between 1991 and 1996, 30 447 subjects were included in the Malmo Diet Cancer
      Study (MDCS). People who developed RA after inclusion were identified by linking
      the MDCS database to different Swedish registers. One matched control for each
      validated case was selected from the MDCS. IgG antibodies against cyclic
      citrullinated peptide (anti-CCP) and mutated citrullinated vimentin (anti-MCV)
      and IgM rheumatoid factor (IgM RF) were determined by ELISA. Serum COMP was
      measured with a sandwich ELISA. RESULTS: 172 incident cases of RA (median time
      from inclusion to diagnosis 5 years; range 1-13) were identified. Pre-RA cases
      were significantly more likely than controls to be positive for anti-CCP (21.9%
      vs 0.6%), anti-MCV (29.6% vs 3.0%) and IgM RF (18.9% vs 2.4%) (all p<0.001).
      Overall, mean serum COMP levels did not differ between cases and controls. Among
      pre-RA cases included 1-3 years before diagnosis, raised COMP (>12 U/l) was seen
      in a greater proportion of anti-CCP-negative than anti-CCP-positive subjects (50%
      vs 15%; p=0.04). CONCLUSIONS: Increased cartilage turnover, measured by COMP, and
      circulating RA-specific antibodies may be distinct processes in the preclinical
      phase of RA.

PMID- 21081528
TI  - A preliminary score for the assessment of disease activity in hereditary
      recurrent fevers: results from the AIDAI (Auto-Inflammatory Diseases Activity
      Index) Consensus Conference.
AB  - BACKGROUND: The systemic autoinflammatory disorders (SAID) share many clinical
      manifestations, albeit with variable patterns, intensity and frequency. A common
      definition of disease activity would be rational and useful in the management of
      these lifelong diseases. Moreover, standardised disease activity scores are
      required for the assessment of new therapies in constant development. The aim of
      this study was to develop preliminary activity scores for familial Mediterranean
      fever, mevalonate kinase deficiency, tumour necrosis factor receptor-1-associated
      periodic syndrome and cryopyrin-associated periodic syndromes (CAPS). METHODS:
      The study was conducted using two well-recognised consensus formation methods:
      the Delphi technique and the nominal group technique. The results from a two-step
      survey and data from parent/patient interviews were used as preliminary data to
      develop the agenda for a consensus conference to build a provisional scoring
      system. RESULTS: 24 of 65 experts in SAID from 20 countries answered the web
      questionnaire and 16 attended the consensus conference. There was consensus
      agreement to develop separate activity scores for each disease but with a common
      format based on patient diaries. Fever and disease-specific clinical variables
      were scored according to their severity. A final score was generated by summing
      the score of all the variables divided by the number of days over which the diary
      was completed. Scores varied from 0 to 16 (0-13 in CAPS). These scores were
      developed for the purpose of clinical studies but could be used in clinical
      practice. CONCLUSION: Using widely recognised consensus formation techniques,
      preliminary scores were obtained to measure disease activity in four main SAID.
      Further prospective validation study of this instrument will follow.

PMID- 21081529
TI  - Limitations in daily activities are the major determinant of reduced health
      related quality of life in patients with hand osteoarthritis.
AB  - OBJECTIVE: To determine the impact of limitations in daily activities and pain on
      quality of life (QoL) in patients with osteoarthritis (OA) visiting a
      rheumatologist. METHODS: Patients diagnosed by the rheumatologist with primary
      hand, knee or hip OA were consecutively included from August 2005 to April 2009.
      QoL was assessed by Short Form-36, with the physical component summary score
      (PCS), calculated using data from a norm-based population. Self-reported pain and
      function in patients with hand OA was assessed by the Australian/Canadian OA hand
      index (AUSCAN) pain (range 0-20) and AUSCAN function (range 0-36). Linear
      regression analyses were performed to investigate associations between PCS and
      demographic characteristics, and between PCS and pain and function in patients
      with OA. RESULTS: Hand OA was diagnosed in 95% of 460 included patients (89%
      women, mean age 61 years). PCS was lowered in patients with OA. Patients with
      hand OA reported a considerable amount of pain (mean 9.5 (SD 4.3)) and disability
      (mean 16.5 (SD 8.6)). AUSCAN function was associated with PCS (adjusted beta=
      0.3, 95% CI -0.4 to -0.2), but AUSCAN pain was not. CONCLUSIONS: Hand OA was the
      most common OA subtype in secondary care. Health-related QoL is decreased in
      patients with OA and is associated with limitations in daily activities.

PMID- 21081530
TI  - Reliability and construct validity of ultrasonography of soft tissue and
      destructive changes in erosive osteoarthritis of the interphalangeal finger
      joints: a comparison with MRI.
AB  - OBJECTIVES: To study the reliability and construct validity of ultrasound in
      interphalangeal finger joints affected by erosive osteoarthritis (EOA) and non
      EOA with MRI as the reference method. METHODS: 252 joints were examined by
      ultrasound, conventional radiography and clinical examination. Ultrasound was
      performed using a high-frequency linear transducer (12 * 18 MHz). On the same
      day, magnetic resonance images of 112 joints were obtained on a 3.0 T magnetic
      resonance unit. The ultrasound and MRI images were re-read independently by other
      readers unaware of the diagnosis, clinical and other imaging findings.
      Interobserver reliability was calculated by the percentage of exact agreement
      obtained and kappa statistics. With MRI as the reference method, the sensitivity
      and specificity of ultrasound in detecting structural (bone erosions and
      osteophytes) and soft tissue (effusion and grey-scale synovitis) changes in EOA
      were calculated. RESULTS: Ultrasound and MRI were found to be more sensitive in
      detecting erosions than conventional radiography in EOA. A high agreement between
      ultrasound and MRI in the assessment of bone erosions (77.7%), osteophytes
      (75.9%) and synovitis (86.5%) was present. A high percentage of inflammatory
      changes was found in EOA, and in smaller amount in non-EOA, both confirmed by
      MRI. Good interobserver reliability of ultrasound was obtained for all variables
      (all median kappa > 0.8). CONCLUSION: Grey-scale ultrasound proved to be a
      reliable and valid imaging technique to assess erosions and soft tissue changes,
      compared with MRI as a reference method in EOA.

PMID- 21081531
TI  - Altered dynamics of transforming growth factor beta(TGF-beta) receptors in
      scleroderma fibroblasts.
AB  - OBJECTIVES: To investigate the difference in the dynamics of transforming growth
      factor beta (TGF-beta) receptors between normal and scleroderma fibroblasts.
      METHODS: The cell surface expression levels of TGF-beta receptors were determined
      by biotinylation and immunoprecipitation assay. The dynamics of TGF-beta
      receptors on the cell surface was determined by the reversible biotinylation
      assay. The subcellular localisation of TGF-beta receptors was determined by
      immunoprecipitation using antibodies against clathrin and caveolin. RESULTS:
      Although the total expression levels of TGF-beta receptors were elevated in
      scleroderma fibroblasts compared with normal fibroblasts, there was no
      significant difference in the cell surface expression levels of TGF-beta
      receptors between these two groups. However, the internalisation rate of TGF-beta
      receptors was higher in scleroderma fibroblasts compared with normal fibroblasts.
      Furthermore, caveolin constitutively made a complex with TGF-beta receptors,
      while the interaction of clathrin with TGF-beta receptors was marginal in
      scleroderma fibroblasts. CONCLUSIONS: The dynamics of TGF-beta receptors on the
      cell surface is accelerated in scleroderma fibroblasts. Considering that the
      activation state of TGF-beta signalling is regulated by a balance between the
      clathrin-dependent internalisation and the lipid raft-caveolar internalisation,
      the accumulation of TGF-beta receptors in caveolin-positive vesicles may result
      in the deceleration of caveolin-dependent internalisation and subsequently lead
      to the relative acceleration of clathrin-dependent internalisation.

PMID- 21081532
TI  - Nuclear inclusions and pseudoinclusions: friends or foes of the surgical
      pathologist?
AB  - Abnormal substances in the nuclei that can be observed by light microscopy are
      often broadly referred to as nuclear inclusions. Although their recognition in
      the appropriate clinicopathological settings can aid in the diagnosis of some
      disease entities and tumor types, they can also be a source of error. There are 2
      morphologically distinct types of inclusions with different mechanisms of
      formation and diagnostic significance, including bona fide nuclear inclusions and
      nuclear pseudoinclusions. Bona fide nuclear inclusions result from accumulation
      in the nuclei of viral particles, cytoplasmic materials (such as surfactant,
      immunoglobulin, and glycogen), biotin, nuclear lamins, or polyglutamine. Some of
      them are diagnostically helpful, such as surfactant inclusion, which can support
      the pulmonary origin of an adenocarcinoma, whereas others may be misleading, such
      as biotin inclusion, which can be mistaken for herpes infection. Nuclear
      pseudoinclusions, which represent invaginations of cytoplasm into the nucleus,
      are delimited by the nuclear membrane. Although not totally specific, they are
      particularly common in papillary thyroid carcinoma, meningioma, and usual ductal
      hyperplasia of the breast and hence may aid in the diagnosis of these entities.
      Nuclear pseudo-pseudoinclusions, which are artefactual bubbles in the nuclei that
      mimic nuclear pseudoinclusions or clear nuclei, can lead to misdiagnosis of
      follicular adenoma or hyperplastic nodule as papillary thyroid carcinoma.

PMID- 21081533
TI  - The Fas-mediated apoptotic pathway in cardiac myxoma.
AB  - Cardiac myxoma is the most common primary tumor of the heart. The existence of
      apoptosis in cardiac myxoma has been demonstrated. The purpose of this
      investigation was to elucidate the pathway of apoptosis and the cell cycle in
      cardiac myxomas. This study had 2 parts: investigation of a cultured cardiac
      myxoma cell line and the analysis of data from 20 patients with cardiac myxoma
      that was surgically excised. Apoptosis signal transduction was determined by
      assessing DNA fragmentation, Fas ligand (FasL), Fas, tumor necrosis factor-alpha
      (TNF-alpha), caspase-3, and terminal deoxynucleotidyl transferase nick-end
      labeling (TUNEL) assay through immunohistochemical stain, quantitative reverse
      transcriptase- polymerase chain reaction (RT-PCR), and Western blot analysis. The
      patient population consisted of 12 (60%) women and 8 (40%) men with a mean age of
      46 years (range = 32-64 years). All cases of myxoma were sporadic myxomas rather
      than familial. Clinical presentations included asymptomatic (26%), dyspnea (44%),
      stroke (9%), chest pain (9%), and fever (11%). All myxomas were located in the
      left atrium. Pathological scores for inflammation, cellularity, calcification,
      and thrombosis were not related to myxoma location or clinical events. In cardiac
      myxoma, apoptosis documented by TUNEL (70.9% +/- 17.6%) and the caspase-3 (66.5%
      +/- 32.5%) final common pathway is characterized by the extrinsic Fas/ FasL
      dependent pathway (positive stained 70.9% +/- 19.2%; 26.0% +/- 17.2%,
      respectively), but not the intrinsic pathway. The RT-PCR and Western Blot
      analysis (Fas/FasL, TNF-alpha, caspase-3, and apoptosis) of the cardiac myxoma
      and cultured cardiac myxoma cells confirmed the immunochemical results. The
      extrinsic Fas/FasL-dependent apoptosis pathways in cardiac myxomas were proved by
      both RNA and protein levels.

PMID- 21081534
TI  - Primitive multipotential primary sarcoma of bone (Polyhistioma) or carcinosarcoma
      metastatic to bone?

PMID- 21081535
TI  - Pleural mesothelioma in situ and its adenocarcinoma simulator.

PMID- 21081536
TI  - 2010 World Cup connections: Paul the octopus in a lymph node aspirate.

PMID- 21081537
TI  - Depression and the delay between symptom onset and hospitalization in heart
      failure patients.
AB  - AIMS: Heart failure (HF) patients frequently suffer from episodes of
      deterioration and may need medical treatment. An adequate reaction from the
      patient is needed to decrease the delay between the onset of deterioration and
      consulting a medical professional (i.e. consulting behaviour). The aim of the
      present study was to evaluate whether depressive symptoms are associated with the
      duration of the delay between the onset of symptoms of worsening HF and
      hospitalization, and to examine how consulting behaviour correlates to depressive
      symptoms and delay in HF patients. METHODS AND RESULTS: Data on the time between
      the onset of symptoms of worsening HF and hospitalization, depressive symptoms,
      and self-care behaviour were collected in 958 HF patients (37% female; age 71 +/-
      11 years; New York Heart Association functional class II-IV), using validated
      questionnaires. The median delay time of the total sample was 72 h (ranging from
      0 to 243 days). Patients with depressive symptoms delayed longer compared with
      those without depressive symptoms (120 vs. 54 h, P= 0.001). Patients with
      depressive symptoms had a 1.5 times higher risk for a delay of >= 72 h,
      independent of demographic and clinical variables (P= 0.008). Consulting
      behaviour did not correlate with depressive symptoms but was weakly associated
      with delay (r= -0.07, P= 0.03). CONCLUSIONS: Heart failure patients with
      depressive symptoms have a significantly longer delay between HF deterioration
      and hospital admission. Interventions designed to improve the consulting
      behaviour in HF patients with depressive symptoms may have a limited effect on
      delay. Further research is needed to obtain more insight into the mechanisms
      underlying the relationship between delay and depression.

PMID- 21081538
TI  - Leveraging guidelines: understanding heart failure, organizing care. Commentary
      on the 2010 NICE chronic heart failure guideline update.

PMID- 21081539
TI  - Lessened decline in physical activity and impairment of older adults with
      diabetes with telemedicine and pedometer use: results from the IDEATel study.
AB  - OBJECTIVE: to examine the effects of the Informatics for Diabetes Education and
      Telemedicine (IDEATel) telemedicine intervention and pedometer use on physical
      activity (PA) and impairment in older adults with diabetes. DESIGN: randomised
      clinical trial. Subjects ethnically diverse medically underserved Medicare
      beneficiaries with diabetes (n= 1,650). METHODS: participants received home
      videovisits with a diabetes educator every 4-6 weeks or usual care. All received
      a pedometer. Annual measurements included hemoglobin A1c, Comprehensive
      Assessment and Referral Evaluation Activities of Daily Living, Diabetes Self-Care
      Activities, Charlson Comorbidity Index, Luben Social Support and pedometer use.
      Mixed model analyses were performed using random effects to adjust for clustering
      within primary care physicians. RESULTS: in the telemedicine group compared with
      the usual care group, the rate of decline in PA (P= 0.0128) and physical
      impairment (PI) (P= 0.0370) was significantly less over time. Significant mean
      endpoint differences were observed for PA (P= 0.003). Pedometer use was
      significantly associated with PA (P= 0.0006) and PI (P< 0.0001). Baseline
      characteristics associated with greater PA included having fewer comorbid
      conditions (P= 0.0054), less depression (P< 0.0001), more social networking (P<
      0.0001), lower BMI (P< 0.0001), male gender (P< 0.0001) and lower hemoglobin A1c
      level (P= 0.0045). Similar predictors were observed for PI, except duration of
      diabetes also predicted increased impairment (P< 0.0001). Significant indirect
      effects were observed through use of the pedometer on reduced decline in PA (P=
      0.0024, 0.0013) and PI (P= 0.0024, P< 0.0001). CONCLUSIONS: this telemedicine
      intervention reduced rates of decline in PA and impairment in older adults with
      diabetes. Pedometers may be a helpful inexpensive adjunct to diabetes initiatives
      delivered remotely with emerging technologies. ClinicalTrials.gov identifier NCT
      00271739.

PMID- 21081540
TI  - Transforming sexuality: the medical sources of Karl Heinrich Ulrichs (1825-95)
      and the origins of the theory of bisexuality.
AB  - This article explores the medical references in the writings of the German jurist
      and activist Karl Heinrich Ulrichs as a means of breaking new ground in diverse
      fields (including history of medicine, history of sexuality, and gender history).
      It demonstrates that the theory of bisexuality has a much deeper and more
      textured genealogy than has been hitherto appreciated and that dual-gendered
      bodies and minds must be better recognized as important through the nineteenth
      century. Specifically, it demonstrates that classifications and rhetoric of
      hermaphroditism, and other dual-gendered categories (e.g., sexual dualism and
      anatomical bisexuality), were deployed in diverse contexts through the period,
      often with little or no reference to the occurrence of genital ambiguities.
      Important discourses in embryology, utilized by Ulrichs, suggested that all
      individuals, in the earliest stages of fetal development, were hermaphroditic. In
      making an analogy among the ontogeny of sex anatomy, hermaphroditism, and the
      development of erotic preferences, Ulrichs sought to naturalize homoeroticism,
      rendering social and legal prohibitions untenable. His advocacy, however, was
      counterbalanced by the Prussian forensic expert Johann Ludwig Casper who had made
      some conceptual maneuvers similar to Ulrichs only couched in the rhetoric of
      pathology. Ulrichs was equivocal in his use of forensic works such as Casper's,
      condemning their authors but recognizing similarities with his own gender schema.

PMID- 21081541
TI  - Skill of frontline workers implementing integrated management of neonatal and
      childhood illness: experience from a district of West Bengal, India.
AB  - A cross-sectional study was conducted in Purulia district, West Bengal, India, to
      assess the skill of 155 frontline workers implementing Integrated Management of
      Neonatal and Childhood Illness (IMNCI) and the logistic support thereof. The
      skills of counting respiratory rate, assessing immunization status in both age
      groups, assessment of breastfeeding in young infants and plotting of weight in a
      growth chart in case of children aged 2-59 months were acquired by majority of
      workers. Around two-thirds workers synthesized correct classification and nearly
      60% gave appropriate management of at least one subgroup. In 30-40% cases, carers
      received feeding advices. Around 50% casesheets were complete and timely report
      submission rate was nearly 70%. Necessary equipments were available with majority
      of workers except the utensils for preparation of ORS. The supply of essential
      drugs varied from 33.5 to 71.6%. These findings suggest that IMNCI program
      offered a scope for capacity-building and infrastructure strengthening of the
      health system.

PMID- 21081542
TI  - Roles of Salmonella multidrug efflux pumps in tigecycline resistance.
AB  - OBJECTIVES: salmonella enterica strains exhibiting decreased susceptibility to
      tigecycline have been reported. In this study, we sought to elucidate the roles
      of Salmonella multidrug efflux pumps and AcrAB regulators in tigecycline
      resistance. METHODS: we examined the involvement of multidrug efflux pumps and
      AcrAB regulators in resistance to tigecycline and other glycylcyclines by
      determining the MICs of the drugs for Salmonella multidrug efflux pump and AcrAB
      regulator-overproducing or -deleted strains. Strains of S. enterica serovar
      Typhimurium derived from the wild-type strain ATCC 14028s were used in this
      study. RESULTS: a plasmid carrying the tet gene conferred resistance to 9-(N,N
      dimethylglycylamido)-6-demethyl-6-deoxytetracycline ('DMG-DMDOT') minocycline,
      doxycycline and tetracycline, but does not affect tigecycline resistance.
      Deletion of acrAB resulted in strains with significantly increased susceptibility
      to tigecycline and other glycylcyclines. Plasmids carrying the acrAB or acrEF
      gene restored increased susceptibility of the acrAB-deleted mutant to all tested
      compounds. Deletion of ramA, a positive regulator of acrAB, slightly increased
      susceptibility to tigecycline. Overexpression of ramA and deletion of ramR, a
      repressor of ramA, resulted in decreased susceptibility to all tested compounds.
      This phenotype, modulated by ramA or ramR, was not observed in the acrB-deleted
      background. CONCLUSIONS: AcrAB and AcrEF confer resistance to tigecycline and
      tetracycline derivatives in Salmonella. RamA and RamR are also involved in
      resistance to tigecycline in an AcrAB-dependent manner.

PMID- 21081543
TI  - Effect of two interventions on reducing antibiotic prescription in pharyngitis in
      primary care.
AB  - OBJECTIVES: to evaluate the effect of two interventions on reducing antibiotic
      prescription in pharyngitis. METHODS: a prospective, non-randomized, before-after
      controlled study was carried out in primary care centres throughout Spain.
      General practitioners (GPs) registered all cases of pharyngitis during a 3 week
      period before and after two types of intervention in 2008 and 2009, respectively.
      Full intervention consisted of discussion sessions of the results of the first
      registry, courses for GPs, guidelines, patient information leaflets, workshops on
      rapid tests and the use of rapid antigen detection tests (RADTs) in their
      consulting offices. The physicians in the partial intervention group underwent
      all the above intervention except for the workshop, and RADTs were not provided.
      A control group was also included in 2009. Multilevel logistic regression was
      performed considering the prescription of antibiotics as the dependent variable.
      RESULTS: a total of 280 GPs registered cases with pharyngitis (70 partial
      intervention and 210 full intervention). Fifty-nine new physicians were included
      as a control group. A total of 6849 episodes of pharyngitis were registered.
      Antibiotic prescription was significantly lower after intervention for the full
      intervention group, but not for the partial intervention group. According to the
      multivariate model, in comparison with the control group, the odds ratio of
      antibiotic prescription after the intervention was 0.52 [95% confidence interval
      (95% CI) 0.23-1.18] in the partial intervention group and 0.23 (95% CI 0.11-0.47)
      in the full intervention group. CONCLUSIONS: intervention was beneficial for
      reducing the prescription of antibiotics, but was only statistically significant
      when the GPs were provided with RADTs.

PMID- 21081545
TI  - Safety and efficacy of CURB65-guided antibiotic therapy in community-acquired
      pneumonia.
AB  - OBJECTIVES: To determine whether the introduction of a community-acquired
      pneumonia (CAP) severity assessment tool to guide antibiotic selection could
      reduce broad-spectrum antibiotic prescribing without compromising patient safety.
      METHODS: A prospective before and after evaluation study. Empirical antibiotic
      prescribing was studied for 18 months from June 2006 to January 2008 (pre
      intervention) and then for 18 months following the implementation of a CURB65
      guided antibiotic therapy guideline in June 2008. The primary outcome was the use
      of broad-spectrum antibiotics (cephalosporin, amoxicillin plus clavulanic acid
      and macrolides) in patients with CAP. Safety outcomes were 30 day mortality,
      requirement for mechanical ventilation and/or vasopressor support (MV/VS),
      development of complicated pneumonia, time to clinical stability (TCS) and length
      of hospital stay. RESULTS: The introduction of CURB65-guided therapy resulted in
      an overall reduction in the prescription of cephalosporins (from 27.1% of
      patients receiving this agent in the overall pre-intervention cohort to 8.0% in
      the post-intervention cohort, P < 0.0001) and macrolides (72.8% to 58.7%, P <
      0.0001), particularly among low-risk patients. There was a corresponding increase
      in the prescription of the narrower-spectrum agent amoxicillin (29.7% to 41.7%, P
      < 0.0001) and an increase in the use of amoxicillin monotherapy (10.4% to 29.9%,
      P < 0.0001). Co-amoxiclav use increased slightly as this agent replaced
      cephalosporins as first-line treatment for severe CAP. The guideline had no
      impact on 30 day mortality, MV/VS, complicated pneumonia, TCS or length of stay.
      Following the intervention, adherence to national guidelines increased from 25.4%
      of prescriptions to 61.9%, suggesting the potential for further improvements.
      CONCLUSIONS: CURB65-guided antibiotic therapy was associated with a significant
      decrease in broad-spectrum antibiotic use. The intervention was safe with no
      impact on mortality, treatment failure or clinical response.

PMID- 21081544
TI  - Different surface charge of colistin-susceptible and -resistant Acinetobacter
      baumannii cells measured with zeta potential as a function of growth phase and
      colistin treatment.
AB  - OBJECTIVES: electrostatic forces mediate the initial interaction between cationic
      colistin and Gram-negative bacterial cells. Lipopolysaccharide (LPS) loss
      mediates colistin resistance in some A. baumannii strains. Our aim was to
      determine the surface charge of colistin-susceptible and -resistant A. baumannii
      as a function of growth phase and in response to polymyxin treatment. METHODS:
      the zeta potential of A. baumannii ATCC 19606 and 10 clinical multidrug-resistant
      strains (MICs 0.5-2 mg/L) was assessed. Colistin-resistant derivatives (MIC >128
      mg/L) of wild-type strains were selected in the presence of 10 mg/L colistin,
      including the LPS-deficient lpxA mutant, ATCC 19606R. To determine the
      contribution of LPS to surface charge, two complemented ATCC 19606R derivatives
      were examined, namely ATCC 19606R + lpxA (containing an intact lpxA gene) and
      ATCC 19606R + V (containing empty vector). Investigations were conducted as a
      function of growth phase and polymyxin treatment (1, 4 and 8 mg/L). RESULTS: wild
      type cells exhibited a greater negative charge (-60.5  +/-  2.36 to -26.2  +/- 
      2.56 mV) thancolistin-resistant cells (-49.2  +/-  3.09 to -19.1  +/-  2.80 mV)
      at mid-log phase (ANOVA, P  <  0.05). Opposing growth-phase trends were observed
      for both phenotypes: wild-type cells displayed reduced negative charge and
      colistin-resistant cells displayed increased negative charge at stationary
      compared with mid-logarithmic phase. Polymyxin exposure resulted in a
      concentration-dependent increase in zeta potential. Examination of ATCC 19606R
      and complemented strains supported the importance of LPS in determining surface
      charge, suggesting a potential mechanism of colistin resistance. CONCLUSIONS:
      zeta potential differences between A. baumannii phenotypes probably reflect
      compositional outer-membrane variations that impact the electrostatic component
      of colistin activity.

PMID- 21081546
TI  - High extracellular levels of cefpirome in unaffected and infected lung tissue of
      patients.
AB  - OBJECTIVES: the objective of the present investigation was to measure the
      extracellular concentrations of cefpirome in unaffected and infected lung tissue
      of septic patients. METHODS: a single intravenous dose of 30 mg/kg total body
      weight of cefpirome was administered to eight patients every 12 h prior to
      insertion of microdialysis probes into lung tissue. RESULTS: the median (minimum,
      maximum) peak concentration (C(max)), time to C(max) (T(max)), area under the
      concentration-time curve from 0 to 4 h (AUC(0-4)) and AUC(0-infinity) of unbound
      cefpirome for unaffected lung were 48 (32, 107) mg/L, 0.83 (0.17, 3.17) h, 117
      (60, 177) mg . h/L and 182 (80, 382) mg . h/L, respectively. The corresponding
      values for infected lung tissue were 45 (6, 122) mg/L, 1.17 (0.83, 2.83) h, 92
      (17, 253) mg . h/L and 206 (49, 379) mg . h/L, respectively. The median apparent
      terminal elimination half-lives (t(&frac12;z)) of cefpirome were 2.61, 3.05 and
      3.39 h for plasma, unaffected lung and infected lung, respectively. The median
      ratios of the AUC(0)(-infinity) for lung to the AUC(0)(-infinity) for plasma were
      0.63 (0.19, 1.55) and 0.46 (0.32, 0.98) for unaffected and infected lung,
      respectively. CONCLUSIONS: we provide strong evidence that cefpirome penetrates
      effectively into the extracellular space fluid of lung tissue. Under steady-state
      conditions, the median concentrations of cefpirome in plasma, unaffected lung and
      infected lung exceeded the MICs of the majority of relevant bacteria over the
      entire dosing interval of up to 12 h after intravenous administration of a dose
      of 30 mg/kg total body weight.

PMID- 21081547
TI  - Contribution of CmeG to antibiotic and oxidative stress resistance in
      Campylobacter jejuni.
AB  - OBJECTIVES: campylobacter jejuni is a leading foodborne pathogen worldwide and
      its resistance to antimicrobials is a major concern for public health. The cmeG
      (Cj1375) gene in C. jejuni encodes a putative efflux transporter of the major
      facilitator family, but its function in antimicrobial resistance has not been
      determined. This study aimed to characterize the function of CmeG in conferring
      resistance to antibiotics and oxidative stress. METHODS: the cmeG gene (Cj1375)
      in C. jejuni was inactivated by insertional mutagenesis and overexpressed by
      cloning with a shuttle vector. These constructs were compared with the wild-type
      strain using antimicrobial susceptibility tests and drug accumulation assays.
      RESULTS: the cmeG mutation reduced bacterial growth and rendered C. jejuni more
      susceptible to ciprofloxacin, erythromycin, gentamicin, tetracycline, rifampicin,
      ethidium bromide and cholic acid as well as hydrogen peroxide, and in trans
      complementation restored the susceptibility to near wild-type level. RT-PCR
      showed that cmeG is co-transcribed with its downstream gene cmeH (Cj1376)
      encoding a putative periplasmic protein, but mutation of cmeH alone did not
      affect the susceptibility to antibiotics. Notably, overexpression of the cmeGH
      operon in C. jejuni NCTC 11168 significantly increased its resistance to
      fluoroquinolones. In addition, the cmeG mutant accumulated more EtBr and
      ciprofloxacin than the wild-type strain. CONCLUSIONS: these results indicate that
      CmeG functions as a multidrug efflux transporter contributing to antibiotic
      resistance and oxidative defence in Campylobacter.

PMID- 21081548
TI  - Escherichia coli O25b-ST131: a pandemic, multiresistant, community-associated
      strain.
AB  - Escherichia coli sequence type 131 (ST131) is a worldwide pandemic clone, causing
      predominantly community-onset antimicrobial-resistant infection. Its pandemic
      spread was identified in 2008 by utilizing multilocus sequence typing (MLST) of
      CTX-M-15 extended-spectrum beta-lactamase-producing E. coli from three
      continents. Subsequent research has confirmed the worldwide prevalence of ST131
      harbouring a broad range of virulence and resistance genes on a transferable
      plasmid. A high prevalence of the clone (~30%-60%) has been identified amongst
      fluoroquinolone-resistant E. coli. In addition, it potentially harbours a variety
      of beta-lactamase genes; most often, these include CTX-M family beta-lactamases,
      and, less frequently, TEM, SHV and CMY beta-lactamases. Our knowledge of ST131's
      geographical distribution is incomplete. A broad distribution has been
      demonstrated amongst antimicrobial-resistant E. coli from human infection in
      Europe (particularly the UK), North America, Canada, Japan and Korea. High rates
      are suggested from limited data in Asia, the Middle East and Africa. The clone
      has also been detected in companion animals, non-companion animals and foods. The
      clinical spectrum of disease described is similar to that for other E. coli, with
      urinary tract infection predominant. This can range from cystitis to life
      threatening sepsis. Infection occurs in humans of all ages. Therapy must be
      tailored to the antimicrobial resistance phenotype of the infecting isolate and
      the site of infection. Phenotypic detection of the ST131 clone is not possible
      and DNA-based techniques, including MLST and PCR, are described.

PMID- 21081549
TI  - Characterization of macrolide resistance genes in Haemophilus influenzae isolated
      from children with cystic fibrosis.
AB  - OBJECTIVES: to determine the mechanism(s) of macrolide resistance in Haemophilus
      influenzae isolated from cystic fibrosis (CF) patients participating in a
      randomized placebo-controlled trial of azithromycin. METHODS: macrolide
      susceptibility, mutations and carriage of the macrolide resistance genes erm(A),
      erm(B), erm(C), erm(F) and mef(A) were determined using PCR assays and sequencing
      or hybridization of the PCR products. H. influenzae isolates were used as donors
      in conjugation studies with H. influenzae and Enterococcus faecalis recipients.
      Transconjugant susceptibility and the macrolide resistance genes carried were
      determined. RESULTS: of the 106 H. influenzae isolates, 27 were resistant and 78
      intermediate resistant to azithromycin and/or erythromycin. All isolates carried
      one or more macrolide resistance gene(s), with the mef(A), erm(B) and erm(F)
      genes found in 74%, 31% and 29% of the isolates, respectively. None of the
      selected isolates had L4 or L22 mutations. Twenty-five donors, with various
      macrolide MICs, transferred macrolide resistance genes to H. influenzae Rd (3.5 *
      10(-7)-1 * 10(-10)) and/or E. faecalis (1 * 10(-7)-1 * 10(-8)) recipients. The H.
      influenzae transconjugants were phenotypically resistant or intermediate to both
      macrolides while E. faecalis transconjugants were erythromycin resistant.
      CONCLUSIONS: this is the first identification of erm(A), erm(C) and erm(F) genes
      in H. influenzae or bacteria from CF patients and the first characterization of
      macrolide gene transfer from H. influenzae donors. The high level of H.
      influenzae macrolide gene carriage suggests that the use of azithromycin in the
      CF population may ultimately reduce the effectiveness of continued or repeated
      macrolide therapy.

PMID- 21081550
TI  - Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic
      lipoprotein subclasses in statin-treated patients with coronary heart disease.
AB  - AIMS: To investigate the effects of secretory phospholipase A2 (sPLA(2))
      inhibition on plasma lipoproteins. Secretory phospholipase A2 isoenzymes promote
      atherosclerosis by mechanisms that include lipoprotein modification, retention,
      and oxidation. METHODS AND RESULTS: Phospholipase Levels And Serological Markers
      of Atherosclerosis II (PLASMA II) is a Phase II, randomized, double-blind,
      placebo-controlled parallel-arm study of two once-daily doses of the novel
      sPLA(2) inhibitor, 1-H-indole-3-glyoxamide or varespladib methyl (Anthera
      Pharmaceuticals, Hayward, CA, USA). One hundred and thirty-five stable coronary
      heart disease patients were treated with either varespladib methyl 250 mg once
      daily, varespladib methyl 500 mg once daily, or placebo for 8 weeks. Varespladib
      methyl treatment resulted in statistically significant dose-dependent reductions
      that were different from placebo in sPLA(2) concentration, low-density
      lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (HDL)
      cholesterol. When compared with placebo, varespladib methyl 500 mg once daily
      reduced LDL cholesterol by 15% (P < 0.001), non-HDL cholesterol by 15% (P <
      0.001), total very LDL (VLDL) particle concentration by 14% (P = 0.022), and
      small VLDL particle concentration by 24% (P = 0.030). Relative to baseline,
      varespladib methyl 500 mg once daily reduced total LDL particle concentration
      (7%, P = 0.002) and small LDL particle concentration (11%, P = 0.014).
      CONCLUSION: Reductions in atherogenic lipoproteins suggest that varespladib
      methyl 500 mg once daily may be an effective anti-atherosclerotic agent. Trial
      registered at ClinicalTrials.gov, identifier: NCT00525954.

PMID- 21081552
TI  - Appropriate set-up of the da Vinci Surgical System in relation to the location of
      anterior and middle mediastinal tumors.
AB  - The da Vinci(r) Surgical System (dV) and its later version [da Vinci S(r)
      Surgical System (dVS)] have been used only in very few cases in selected thoracic
      surgical areas in Japan. Recently, we used the dV and dVS for various types of
      anterior and middle mediastinal tumors in clinical practice. We report our
      experience, and review the settings which depended on tumor location. Six
      patients gave written informed consent to undergo robotic surgery using the dV or
      dVS. We evaluated the feasibility, safety and appropriate settings of this system
      for the surgical treatment of mediastinal tumors. Tumor dissection was performed
      by two specialists in thoracic surgery certified to use the dV and dVS, and
      another specialist who acted as an assistant. We were able to access difficult-to
      reach areas like the mediastinum. All the resected tumors were classified as
      benign tumors histologically. Crucial to the success of these operations was the
      set-up of the dV, which varied according to the location of mediastinal tumors.
      Robotic surgery enables various types of mediastinal tumor dissection more safely
      and easily than conventional video-assisted thoracoscopic surgery (VATS). The dV
      requires the appropriate set-up configuration, which varies according to the
      location of the mediastinal tumor.

PMID- 21081551
TI  - Impaired consciousness in temporal lobe seizures: role of cortical slow activity.
AB  - Impaired consciousness requires altered cortical function. This can occur either
      directly from disorders that impair widespread bilateral regions of the cortex or
      indirectly through effects on subcortical arousal systems. It has therefore long
      been puzzling why focal temporal lobe seizures so often impair consciousness.
      Early work suggested that altered consciousness may occur with bilateral or
      dominant temporal lobe seizure involvement. However, other bilateral temporal
      lobe disorders do not impair consciousness. More recent work supports a 'network
      inhibition hypothesis' in which temporal lobe seizures disrupt brainstem
      diencephalic arousal systems, leading indirectly to depressed cortical function
      and impaired consciousness. Indeed, prior studies show subcortical involvement in
      temporal lobe seizures and bilateral frontoparietal slow wave activity on
      intracranial electroencephalography. However, the relationships between
      frontoparietal slow waves and impaired consciousness and between cortical slowing
      and fast seizure activity have not been directly investigated. We analysed
      intracranial electroencephalography recordings during 63 partial seizures in 26
      patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural
      responsiveness was determined based on blinded review of video during seizures
      and classified as impaired (complex-partial seizures) or unimpaired (simple
      partial seizures). We observed significantly increased delta-range 1-2 Hz slow
      wave activity in the bilateral frontal and parietal neocortices during complex
      partial compared with simple-partial seizures. In addition, we confirmed prior
      work suggesting that propagation of unilateral mesial temporal fast seizure
      activity to the bilateral temporal lobes was significantly greater in complex
      partial than in simple-partial seizures. Interestingly, we found that the signal
      power of frontoparietal slow wave activity was significantly correlated with the
      temporal lobe fast seizure activity in each hemisphere. Finally, we observed that
      complex-partial seizures were somewhat more common with onset in the language
      dominant temporal lobe. These findings provide direct evidence for cortical
      dysfunction in the form of bilateral frontoparietal slow waves associated with
      impaired consciousness in temporal lobe seizures. We hypothesize that bilateral
      temporal lobe seizures may exert a powerful inhibitory effect on subcortical
      arousal systems. Further investigations will be needed to fully determine the
      role of cortical-subcortical networks in ictal neocortical dysfunction and may
      reveal treatments to prevent this important negative consequence of temporal lobe
      epilepsy.

PMID- 21081553
TI  - Prevention of postoperative pericardial adhesions in children with hypoplastic
      left heart syndrome.
AB  - Reoperations for congenital cardiac defects are associated with an increased
      surgical risk due to adhesions. We compared the capability of a
      polytetrafluoroethylene (PTFE) membrane, synthetic polyethyleneglycol hydrogel
      (PEG), and a combination of them to prevent postoperative pericardial adhesions
      in patients with hypoplastic left heart syndrome (HLHS). Eighteen consecutive
      patients with HLHS were included. At the end of the Norwood I operation the
      cranial and the caudal half of the heart of each patient was randomized to
      receive a PTFE membrane, a synthetic PEG, a combination of them, or no treatment
      (control). Tenacity and density of adhesions, epicardial visibility, and
      adhesions between the heart and the sternum were analyzed semiquantitatively at a
      subsequent bidirectional Glenn operation. The PTFE membrane significantly
      decreased adhesion formation between the heart and the sternum (P<0.001).
      However, the PTFE membrane, with or without synthetic PEG, impaired epicardial
      visibility (P<0.05) when compared to synthetic PEG or controls. Synthetic PEG
      alone did not significantly reduce the formation of pericardial adhesions.
      Tenacity and density of adhesions were not affected by any of the treatment
      modalities. The PTFE membrane significantly decreases postoperative adhesions
      between the heart and the sternum, but impairs epicardial visibility. Synthetic
      PEG does not prevent formation of pericardial adhesions.

PMID- 21081554
TI  - In patients with concomitant aortic and mitral valve disease is aortic valve
      replacement with mitral valve repair superior to double valve replacement?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: in patients with concomitant aortic and
      mitral valve disease is aortic valve replacement with mitral valve plasty (MVP)
      superior to double valve replacement (DVR) in terms of improved long-term
      survival? Altogether 156 papers were found using the reported search, of which
      seven represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. Out of seven papers,
      that simultaneously compare these two treatment modalities, three favor MVP
      combined with aortic valve replacement (AVR) over DVR, two papers advocate the
      opposite and two failed to find any significant difference in long-term survival,
      freedom from reoperation and thromboembolic and bleeding complications between
      these two surgical options. All data presented derive from level 2b evidence.
      Critical appraisal of these studies is constricted by the large heterogeneity of
      the patients, diversity in treatment protocols and inherent selection bias. We
      conclude that currently the available evidence is insufficient to prove that AVR
      with MVP is superior to DVR in patients with double valve disease.

PMID- 21081555
TI  - Can intracoronary stem cell injection permanently improve cardiac function after
      myocardial infarction?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'Can intracoronary stem cell injection
      permanently improve cardiac function after myocardial infarction?'. Altogether
      314 papers were found using the reported search, of which five represented the
      best evidence to answer the clinical question. The authors, journal, date and
      country of publication, patient group studied, study type, relevant outcomes and
      results of these papers are tabulated. We conclude that stem cells may have
      controversial effects on cardiac function in long-term follow-up of more than two
      years as they improved the left ventricular ejection fraction and end systolic
      volume index just in two studies in which none of them utilized cardiac magnetic
      resonance imaging (MRI), as the most reliable method, to quantify cardiac
      function. However, all remaining three trials which reported negative results
      used cardiac MRI for assessment of cardiac indexes which may be more precise and
      accurate than echocardiographic assessments. So the reliability of the positive
      trials is lower than negative resulted trials in terms of cardiac function
      assessment method. Stem cell therapy almost always offered short-term benefits
      over the best medical treatment, but the long-term benefits are still a matter of
      debate.

PMID- 21081556
TI  - Postoperative complications and respiratory function following segmentectomy of
      the lung - comparison of the methods of making an inter-segmental plane.
AB  - Segmentectomy could be one of the standard modes of surgery for the treatment of
      early lung cancer. However, segmentectomy could be more difficult than lobectomy
      as to the management of inter-segmental plane. The relationship between methods
      of dividing an inter-segmental plane and postoperative complication/pulmonary
      function was investigated in this study. A retrospective study was conducted on
      49 patients who underwent segmentectomy of the lung between February 2008 and
      April 2009 at our institute. Eighteen (36.7%) were male and 31 (63.3%) were
      female. The inter-segmental plane was divided with only a mechanical stapler in
      18 patients, and electrocautery was used in the other 31 patients. There were no
      significant relationships between clinicopathological features and both
      procedures, except gender, operative time, and pleurodesis (P<0.05). Preserved
      forced expiratory volume in one second (FEV(1)) was not affected by the
      procedures. Patients who underwent left upper division segmentectomy had
      significantly more complications. On multivariate analysis, resected segment and
      intraoperative blood loss were found to be significant predictors for
      postoperative complications. There were no significant relationships between the
      methods of making inter-segmental planes and postoperative complications and/or
      lung functions. Resected segment and intraoperative blood loss were predictors
      for postoperative complication in segmental resection of the lung.

PMID- 21081557
TI  - The pericardial window: is a video-assisted thoracoscopy approach better than a
      surgical approach?
AB  - OBJECTIVES: The approach to the pericardial window in patients with pericardial
      effusion (PE) remains undefined as to whether a surgical (transthoracic or
      subxiphoid) or a thoracoscopic pericardial window is the optimal operative
      approach to PE. We hypothesized that the window into the pleural space created by
      the thoracoscopy might improve the outcome. METHODS: We conducted a prospective
      study between September 2007 and October 2009. All patients with PE diagnosed by
      echocardiography who attended the Cardiothoracic Department in King Fahd Hospital
      are included in this study. They were 30 patients (18 males, 12 females aged 44+/
      1.22 years). Patients were subdivided into two groups. Group A, 15 patients
      underwent the surgical (transthoracic or subxiphoid) procedure and Group B, 15
      patients underwent the video-assisted thoracoscopy procedure. Preoperative,
      intraoperative and postoperative variables, morbidity, recurrence, and survival
      were compared in both groups. RESULTS: Preoperative variables were well-matched
      for age, sex, preoperative tamponade, echocardiographical characteristics and co
      morbidities between both groups. No recurrence of effusion was observed in the
      two groups. Operative time was statistically highly significant (P<0.001); it was
      longer in Group B. There was no intraoperative complication in both groups. There
      was no postoperative complication in both groups except one case of superficial
      wound infection in Group A. There was no significance difference between both
      groups as regard duration of chest tube drainage and length of hospital stay.
      There was no in-hospital mortality in both groups. CONCLUSIONS: Pericardial
      window by video-assisted thoracoscopy is an effective technique for pericardial
      drainage and biopsy. Apart from its diagnostic value, it allows the physician to
      fashion a pleuropericardial window for effective drainage while avoiding the
      complications of classic surgical procedures.

PMID- 21081558
TI  - PHOSIDA 2011: the posttranslational modification database.
AB  - The primary purpose of PHOSIDA (http://www.phosida.com) is to manage
      posttranslational modification sites of various species ranging from bacteria to
      human. Since its last report, PHOSIDA has grown significantly in size and evolved
      in scope. It comprises more than 80,000 phosphorylated, N-glycosylated or
      acetylated sites from nine different species. All sites are obtained from high
      resolution mass spectrometric data using the same stringent quality criteria. One
      of the main distinguishing features of PHOSIDA is the provision of a wide range
      of analysis tools. PHOSIDA is comprised of three main components: the database
      environment, the prediction platform and the toolkit section. The database
      environment integrates and combines high-resolution proteomic data with multiple
      annotations. High-accuracy species-specific phosphorylation and acetylation site
      predictors, trained on the modification sites contained in PHOSIDA, allow the in
      silico determination of modified sites on any protein on the basis of the primary
      sequence. The toolkit section contains methods that search for sequence motif
      matches or identify de novo consensus, sequences from large scale data sets.

PMID- 21081560
TI  - PhEVER: a database for the global exploration of virus-host evolutionary
      relationships.
AB  - Fast viral adaptation and the implication of this rapid evolution in the
      emergence of several new infectious diseases have turned this issue into a major
      challenge for various research domains. Indeed, viruses are involved in the
      development of a wide range of pathologies and understanding how viruses and host
      cells interact in the context of adaptation remains an open question. In order to
      provide insights into the complex interactions between viruses and their host
      organisms and namely in the acquisition of novel functions through exchanges of
      genetic material, we developed the PhEVER database. This database aims at
      providing accurate evolutionary and phylogenetic information to analyse the
      nature of virus-virus and virus-host lateral gene transfers. PhEVER
      (http://pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous
      families both (i) between sequences from different viruses and (ii) between viral
      sequences and sequences from cellular organisms. PhEVER integrates extensive data
      from up-to-date completely sequenced genomes (2426 non-redundant viral genomes,
      1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants
      to vertebrates) and offers a clustering of proteins into homologous families
      containing at least one viral sequences, as well as alignments and phylogenies
      for each of these families. Public access to PhEVER is available through its
      webpage and through all dedicated ACNUC retrieval systems.

PMID- 21081559
TI  - Extensive role of the general regulatory factors, Abf1 and Rap1, in determining
      genome-wide chromatin structure in budding yeast.
AB  - The packaging of eukaryotic DNA into chromatin has profound consequences for gene
      regulation, as well as for other DNA transactions such as recombination,
      replication and repair. Understanding how this packaging is determined is
      consequently a pressing problem in molecular genetics. DNA sequence, chromatin
      remodelers and transcription factors affect chromatin structure, but the scope of
      these influences on genome-wide nucleosome occupancy patterns remains uncertain.
      Here, we use high resolution tiling arrays to examine the contributions of two
      general regulatory factors, Abf1 and Rap1, to nucleosome occupancy in
      Saccharomyces cerevisiae. These factors have each been shown to bind to a few
      hundred promoters, but we find here that thousands of loci show localized regions
      of altered nucleosome occupancy within 1 h of loss of Abf1 or Rap1 binding, and
      that altered chromatin structure can occur via binding sites having a wide range
      of affinities. These results indicate that DNA-binding transcription factors
      affect chromatin structure, and probably dynamics, throughout the genome to a
      much greater extent than previously appreciated.

PMID- 21081562
TI  - COXPRESdb: a database to compare gene coexpression in seven model animals.
AB  - Publicly available databases of coexpressed gene sets are a valuable resource for
      a wide variety of experimental studies, including gene targeting for functional
      identification, and for investigations of regulatory mechanisms or protein
      protein interaction networks. Although coexpressed gene databases are becoming
      more and more popular in the field of plant biology, those with animal data are
      rather limited, possibly due to the lower reliability of the coexpression data.
      The original COXPRESdb (coexpressed gene database) (http://coxpresdb.jp)
      represented the coexpression relationship for human and mouse. Here, we report
      updates of this database that especially focus on the enhancement of the
      reliability of gene coexpression data in animals. For this purpose, we
      implemented a new comparable coexpression measure, Mutual Rank, included five
      other animal species, rat, chicken, zebrafish, fly and nematoda, to assess the
      conservation of coexpression, and added different layers of omics data into the
      integrated network of genes. Comparison of coexpression is a key concept to
      enhance the reliability of gene coexpression, and the integration of different
      information can reduce the noise inherent in the information. With the functions
      for gene network representation, COXPRESdb can help researchers to clarify the
      functional and regulatory networks of genes in a broad array of animal species.

PMID- 21081561
TI  - BISC: binary subcomplexes in proteins database.
AB  - Binary subcomplexes in proteins database (BISC) is a new protein-protein
      interaction (PPI) database linking up the two communities most active in their
      characterization: structural biology and functional genomics researchers. The
      BISC resource offers users (i) a structural perspective and related information
      about binary subcomplexes (i.e. physical direct interactions between proteins)
      that are either structurally characterized or modellable entries in the main
      functional genomics PPI databases BioGRID, IntAct and HPRD; (ii) selected web
      services to further investigate the validity of postulated PPI by inspection of
      their hypothetical modelled interfaces. Among other uses we envision that this
      resource can help identify possible false positive PPI in current database
      records. BISC is freely available at http://bisc.cse.ucsc.edu.

PMID- 21081563
TI  - Lipomatous metaplasia within an old anterior myocardial infarction.

PMID- 21081564
TI  - Coda. Our debt to innovation.

PMID- 21081565
TI  - Positron emission tomography in the diagnosis of eosinophilic fasciitis.

PMID- 21081566
TI  - A method for calculating the dose length product from CT DICOM images.
AB  - OBJECTIVE: The dosimetric calculations in CT examinations are currently based on
      two quantities: the volume weighted CT dose index (CTDI(vol)) and the dose-length
      product (DLP). The first quantity is dependent on the exposure factors, scan
      field of view, collimation and pitch factor selections, whereas the second is
      additionally dependent on the scan length. METHODS: In this study a method for
      the calculation of these quantities from digital imaging and communication in
      medicine (DICOM) CT images is presented that allows an objective audit of patient
      doses. This method was based on software that has been developed to enable the
      automatic extraction of the DICOM header information of each image (relating to
      the parameters that affect the aforementioned quantities) into a spreadsheet with
      embedded functions for calculating the contribution of each image to the
      CTDI(vol) and DLP values. The applicability and accuracy of this method was
      investigated using data from actual examinations carried out in three different
      multislice CT scanners. These examinations have been performed with the automatic
      exposure control systems activated, and therefore the tube current and tube
      loading values varied during the scans. RESULTS: The calculated DLP values were
      in good agreement (+/-5%) with the displayed values. The calculated average
      CDTI(vol) values were in similar agreement with the displayed CTDI(vol) values
      but only for two of the three scanners. In the other scanner the displayed
      CTDI(vol) values were found to be overestimated by about 25%. As an additional
      application of this method the differences among the tube modulation techniques
      used by the three CT scanners were investigated. CONCLUSION: This method is a
      useful tool for radiation dose surveys.

PMID- 21081567
TI  - Micro-CT enables microlocalisation and quantification of Her2-targeted gold
      nanoparticles within tumour regions.
AB  - OBJECTIVES: Gold nanoparticles are of interest as potential in vivo diagnostic
      and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and
      radiation enhancers. The aim of this study was to quantitatively determine their
      targeting and microlocalisation in mouse tumour models after intravenous
      injection by using micro-CT. METHODS: Gold nanoparticles (15 nm) were coated with
      polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin).
      In vitro, conjugates incubated with Her2+ (BT-474) and Her2- (MCF7) human breast
      cancer cells showed specific targeted binding with a Her2+ to Her2- gold ratio of
      39.4+/-2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2-
      human breast tumours in opposite thighs were prepared. Gold nanoparticles alone,
      conjugated to Herceptin or to a non-specific antibody were compared. After
      intravenous injection of the gold nanoparticles, gold concentrations were
      determined by atomic absorption spectroscopy. Microlocalisation of gold was
      carried out by calibrated micro-CT, giving both the radiodensities and gold
      concentrations in tumour and non-tumour tissue. RESULTS: All gold nanoparticle
      constructs showed accumulation, predominantly at tumour peripheries. However, the
      Herceptin-gold nanoparticles showed the best specific uptake in their periphery
      (15.8+/-1.7% injected dose per gram), 1.6-fold higher than Her2- tumours and 22
      fold higher than surrounding muscle. Imaging readily enabled detection of small,
      1.5 mm-thick tumours. CONCLUSION: In this pre-clinical study, antibody-targeted
      15 nm gold nanoparticles showed preferential uptake in cognate tumours, but even
      untargeted gold nanoparticles enhanced the visibility of tumour peripheries and
      enabled detection of millimetre-sized tumours. Micro-CT enabled quantification
      within various regions of a tumour.

PMID- 21081568
TI  - The use of joint-specific and whole-body MRI in osteonecrosis: a study in
      patients with juvenile systemic lupus erythematosus.
AB  - OBJECTIVE: This study aimed to estimate the prevalence of osteonecrosis (ON) in
      juvenile systemic lupus erythematosus (SLE) patients using joint-specific and
      whole-body MRI; to explore risk factors that are associated with the development
      of ON; and to evaluate prospectively patients 1 year after initial imaging.
      METHOD: Within a 2 year period, we studied 40 juvenile SLE patients (aged 8-18
      years) with a history of steroid use of more than 3 months duration. Risk factors
      including disease activity, corticosteroid use, vasculitis, Raynaud's phenomenon
      and lipid profile were evaluated. All patients underwent MRI of the hips, knees
      and ankles using joint-specific MRI. Whole-body STIR (short tau inversion
      recovery) MRI was performed in all patients with ON lesions. RESULTS:
      Osteonecrosis was identified in 7 patients (17.5 %) upon joint-specific MRI.
      Whole-body STIR MRI detected ON in 6 of these 7 patients. There was no
      significant difference between the ON and non-ON groups in the risk factors
      studied. One patient had pre-existing symptomatic ON. At 1 year follow-up, the ON
      lesions had resolved in one patient, remained stable in four and decreased in
      size in two. No asymptomatic patients with ON developed clinical manifestations.
      CONCLUSION: Whole-body STIR MRI may be useful in detecting ON lesions in juvenile
      SLE patients but larger studies are needed to define its role.

PMID- 21081569
TI  - Hepatocellular carcinoma in cirrhotic patients at multidetector CT: hepatic
      venous phase versus delayed phase for the detection of tumour washout.
AB  - OBJECTIVES: Our aim was to compare retrospectively hepatic venous and delayed
      phase images for the detection of tumour washout during multiphasic multidetector
      row CT (MDCT) of the liver in patients with hepatocellular carcinoma (HCC).
      METHODS: 30 cirrhotic patients underwent multiphasic MDCT in the 90 days before
      liver transplantation. MDCT was performed before contrast medium administration
      and during hepatic arterial hepatic venous and delayed phases, images were
      obtained at 12, 55 and 120 s after trigger threshold. Two radiologists
      qualitatively evaluated images for lesion attenuation. Tumour washout was
      evaluated subjectively and objectively. Tumour-to-liver contrast (TLC) was
      measured for all pathologically proven HCCs. RESULTS: 48 HCCs were detected at
      MDCT. 46 of the 48 tumours (96%) appeared as either hyper- or isoattenuating
      during the hepatic arterial phase subjective washout was present in 15 HCCs (33%)
      during the hepatic venous phase and in 35 (76%) during the delayed phase
      (p<0.001, McNemar's test). Objective washout was present in 30 of the 46 HCCs
      (65%) during the hepatic venous phase and in 42 of the HCCs (91%) during the
      delayed phase (p=0.001). The delayed phase yielded significantly higher mean TLC
      absolute values compared with the hepatic venous phase (-16.1+/-10.8 HU vs 
      10.5+/-10.2 HU; p<0.001). CONCLUSIONS: The delayed phase is superior to the
      hepatic venous phase for detection of tumour washout of pathologically proven HCC
      in cirrhotic patients.

PMID- 21081570
TI  - Use of small bowel imaging for the diagnosis and staging of Crohn's disease--a
      survey of current UK practice.
AB  - OBJECTIVES: This study used a postal survey to assess the current use of small
      bowel imaging investigations for Crohn's disease within National Health Service
      (NHS) radiological practice and to gauge gastroenterological referral patterns.
      METHODS: Similar questionnaires were posted to departments of radiology (n = 240)
      and gastroenterology (n = 254) identified, by the databases of the Royal College
      of Radiologists and British Society of Gastroenterologists. Questionnaires
      enquired about the use of small bowel imaging in the assessment of Crohn's
      disease. In particular, questionnaires described clinical scenarios including
      first diagnosis, disease staging and assessment of suspected extraluminal
      complications, obstruction and disease flare. The data were stratified according
      to patient age. RESULTS: 63 (27%) departments of radiology (20 in teaching
      hospitals and 43 in district general hospitals (DGHs)) and 73 (29%) departments
      of gastroenterology replied. These departments were in 119 institutions. Of the
      63 departments of radiology, 55 (90%) routinely performed barium follow-though
      (BaFT), 50 (80%) CT, 29 (46%) small bowel ultrasound (SbUS) and 24 (38%) small
      bowel MRI. BaFT was the most commonly used investigation across all age groups
      and indications. SbUS was used mostly for patients younger than 40 years of age
      with low index of clinical suspicion for Crohn's disease (in 44% of radiology
      departments (28/63)). MRI was most frequently used in patients under 20 years of
      age for staging new disease (in 27% of radiology departments (17/63)) or in whom
      obstruction was suspected (in 29% of radiology departments (18/63)). CT was
      preferred for suspected extraluminal complications or obstruction (in 73% (46/63)
      and 46% (29/63) of radiology departments, respectively). Gastroenterological
      referrals largely concurred with the imaging modalities chosen by radiologists,
      although gastroenterologists were less likely to request SbUS and MRI.
      CONCLUSION: BaFT remains the mainstay investigation for luminal small bowel
      Crohn's disease, with CT dominating for suspected extraluminal complications.
      There has been only moderate dissemination of the use of MRI and SbUS.

PMID- 21081571
TI  - Screening for atherosclerotic plaques in the abdominal aorta in high-risk
      patients with multicontrast-weighted MRI: a prospective study at 3.0 and 1.5
      tesla.
AB  - OBJECTIVE: This prospective study compares MRI of atherosclerotic plaque in the
      abdominal aorta at 3 T with that at 1.5 T in patients suffering from hereditary
      hyperlipidaemia, a major risk factor for atherosclerosis. METHODS: MRI of the
      abdominal aorta at 1.5 and 3 T was performed in 21 patients (mean age 58 years).
      The study protocol consisted of proton density (PD), T(1), T(2) and fat-saturated
      T(2) weighted black blood images of the abdominal aorta in corresponding
      orientation. Two independent radiologists performed image rating. First, image
      quality was rated on a five-point scale. Second, atherosclerotic plaques were
      scored according to the modified American Heart Association (AHA) classification
      and analysed for field strength-related differences. Weighted kappa statistics
      were calculated to assess interobserver agreement. RESULTS: Interobserver
      agreement was substantial for nearly all categories. MRI at 3 T offered superior
      image quality in all contrast weightings, most significantly in T(1) and T(2)
      weighted techniques. Plaque burden in the study collective was unexpectedly
      moderate. The majority of plaques were classified as AHA III lesions; no lesions
      were classified above AHA V. There was no significant influence of the field
      strength regarding the AHA classification. CONCLUSION: Abdominal aortal plaque
      screening is basically feasible at both field strengths, whereas the image
      quality is rated superior at 3 T. However, the role of the method in clinical
      practice remains uncertain, since substantial findings in the high-risk
      collective were scarce.

PMID- 21081572
TI  - Image quality of multiplanar reconstruction of pulmonary CT scans using adaptive
      statistical iterative reconstruction.
AB  - OBJECTIVE: We investigated the image quality of multiplanar reconstruction (MPR)
      using adaptive statistical iterative reconstruction (ASIR). METHODS: Inflated and
      fixed lungs were scanned with a garnet detector CT in high-resolution mode (HR
      mode) or non-high-resolution (HR) mode, and MPR images were then reconstructed.
      Observers compared 15 MPR images of ASIR (40%) and ASIR (80%) with those of ASIR
      (0%), and assessed image quality using a visual five-point scale (1, definitely
      inferior; 5, definitely superior), with particular emphasis on normal pulmonary
      structures, artefacts, noise and overall image quality. RESULTS: The mean overall
      image quality scores in HR mode were 3.67 with ASIR (40%) and 4.97 with ASIR
      (80%). Those in non-HR mode were 3.27 with ASIR (40%) and 3.90 with ASIR (80%).
      The mean artefact scores in HR mode were 3.13 with ASIR (40%) and 3.63 with ASIR
      (80%), but those in non-HR mode were 2.87 with ASIR (40%) and 2.53 with ASIR
      (80%). The mean scores of the other parameters were greater than 3, whereas those
      in HR mode were higher than those in non-HR mode. There were significant
      differences between ASIR (40%) and ASIR (80%) in overall image quality (p<0.01).
      Contrast medium in the injection syringe was scanned to analyse image quality;
      ASIR did not suppress the severe artefacts of contrast medium. CONCLUSION: In
      general, MPR image quality with ASIR (80%) was superior to that with ASIR (40%).
      However, there was an increased incidence of artefacts by ASIR when CT images
      were obtained in non-HR mode.

PMID- 21081573
TI  - Ipsilateral atrophy of paraspinal and psoas muscle in unilateral back pain
      patients with monosegmental degenerative disc disease.
AB  - OBJECTIVES: The aim of this study was to assess the cross-sectional area (CSA) of
      both paraspinal and psoas muscles in patients with unilateral back pain using MRI
      and to correlate it with outcome measures. METHODS: 40 patients, all with
      informed consent, with a minimum of 3 months of unilateral back pain with or
      without sciatica and one-level disc disease on MRI of the lumbosacral spine were
      included. Patients were evaluated with self-report measures regarding pain
      (visual analogue score) and disability (Oswestry disability index). The CSA of
      multifidus, erector spinae, quadratus lumborum and psoas was measured at the disc
      level of pathology and the two adjacent disc levels, bilaterally. Comparison of
      CSAs of muscles between the affected vs symptomless side was carried out with
      Student's t-test and correlations were conducted with Spearman's test. RESULTS:
      The maximum relative muscle atrophy (% decrease in CSA on symptomatic side)
      independent of the level was 13.1% for multifidus, 21.8% for erector spinae,
      24.8% for quadratus lumborum and 17.1% for psoas. There was significant
      difference (p<0.05) between sides (symptomatic and asymptomatic) in CSA of
      multifidus, erector spinae, quadratus lumborum and psoas. However, no
      statistically significant correlation was found between the duration of symptoms
      (average 15.5 months), patient's pain (average VAS 5.3) or disability (average
      ODI 25.2) and the relative muscle atrophy. CONCLUSION: In patients with long
      standing unilateral back pain due to monosegmental degenerative disc disease,
      selective multifidus, erector spinae, quadratus lumborum and psoas atrophy
      develops on the symptomatic side. Radiologists and clinicians should evaluate
      spinal muscle atrophy of patients with persistent unilateral back pain.

PMID- 21081574
TI  - The value of dual-time-point 18F-FDG PET/CT for identifying axillary lymph node
      metastasis in breast cancer patients.
AB  - OBJECTIVE: The sensitivity of 18-fluorodeoxyglucose ((18)F-FDG) positron emission
      tomography (PET) for detecting axillary lymph node (ALN) metastases in breast
      cancer is reported to be low. Several studies have shown, however, that dual-time
      point (18)F-FDG PET imaging provides improved accuracy in the diagnosis of
      certain primary tumours when compared with single-scan imaging. The purpose of
      this study was to assess whether the use of dual-time-point (18)F-FDG PET/CT
      scans could improve the diagnostic accuracy of ALN metastasis in breast cancer.
      METHOD: The study included 171 breast cancer patients who underwent pre-operative
      (18)F-FDG PET/CT scans at 2 time-points, the first at 1 h after radiotracer
      injection and the second 3 h after injection. Where (18)F-FDG uptake was in the
      ALN perceptibly increased, the maximum standardised uptake values for both time
      points (SUVmax1 and SUVmax2) and the retention index (RI) were calculated.
      Correlation between the PET/CT results and post-operative histological results
      was assessed. RESULTS: The performance of 1 h and 3 h PET/CT scans was equal,
      with sensitivity 60.3% and specificity 84.7%, in detecting ALN metastasis. Out of
      171 patients, 60 had ALNs with increased (18)F-FDG uptake on 1 h or 3 h images.
      There was no significant difference in RI between the metastatic ALN-positive
      group and the node-negative group. The area under the receiver operating
      characteristic (ROC) curve for SUVmax1 was 0.90 (p<0.001) and 0.87 for SUVmax2
      (p<0.001). CONCLUSION: Dual time-point imaging did not improve the overall
      performance of (18)F-FDG PET/CT in detecting ALN metastasis in breast cancer
      patients.

PMID- 21081575
TI  - Right thoracic paravertebral anaesthesia for percutaneous radiofrequency ablation
      of liver tumours.
AB  - OBJECTIVES: Percutaneous radiofrequency ablation (PRFA) of liver tumours
      performed under local anaesthesia and intravenous sedation can cause severe pain
      to patients. This prospective study evaluated the efficacy of a right thoracic
      paravertebral block (TPVB) for anaesthesia and analgesia during PRFA of liver
      tumours. METHODS: 20 patients, aged 44-74 years, with liver malignancies received
      a multiple injection TPVB at the T6-10 levels 30 min before the PRFA. An
      intravenous infusion of propofol (3-5 mg kg(-1) h(-1)) was administered to
      patients who requested to be sedated and intravenous fentanyl (25 ug bolus) was
      administered as rescue analgesia. Pain during the TPVB and PRFA was assessed
      using a numerical rating scale (NRS; 0, no pain; 10, worst imaginable pain).
      Patients were also assessed for residual pain and analgesic consumption during
      the 24 h after the intervention. RESULTS: The TPVB was well tolerated and
      produced ipsilateral sensory anaesthesia with satisfactory spread (median
      (range); 8 (6-11) dermatomes). The PRFA procedure caused mild pain (mean
      (standard deviation, SD); NRS 1.4 (1.9)) during the insertion of the ablation
      needle and the peak pain intensity during the therapeutic burn was moderate (mean
      (SD); NRS 5.0 (3.3)) in severity. During the 24 h after the PRFA, patients
      reported minimal pain and consumed very few analgesics. The mean (SD)
      satisfaction score (0, totally dissatisfied; 10, very satisfied) of the patients
      was 8.9 (1.1) and that of the radiologists was 8.8 (1.4). CONCLUSION: A right
      TPVB is safe and effective for anaesthesia and analgesia during PRFA of malignant
      liver tumours.

PMID- 21081576
TI  - Statistical analysis of mammographic breast composition measurements: towards a
      quantitative measure of relative breast cancer risk.
AB  - OBJECTIVE: A number of studies have identified the relationship between the
      visual appearance of high breast density at mammography and an increased risk of
      breast cancer. With the advent of digital mammography and the promise of routine
      measurements of parameters associated with breast composition, the possibility
      arises of using breast composition in a quantitative manner to predict relative
      breast cancer risk. Previous measurements have shown that the average proportion
      of glandular and adipose tissue within the breast varies with both age and breast
      size. In order to be able to identify individual women with an unusually high
      volume of glandular tissue, it will therefore be necessary to make comparisons
      with a disease-free population matched for age and breast size. METHODS: A large
      number of breast glandular thickness measurements were analysed to investigate
      the statistics of breast composition across a disease-free population as a test
      of a suitable methodology for relative risk estimation. The large data set is
      also used to revisit the trends in breast composition used in the current UK
      method of breast radiation dosimetry. RESULTS: It is demonstrated that a non
      linear transformation can be used to produce normal statistical distributions,
      suitable for producing a standardised "Z-score" for breast composition.
      CONCLUSION: A standard "Z-score" approach to identify women with unusually
      glandular breasts is recommended and so provide a basis for cancer risk
      estimations.

PMID- 21081577
TI  - Air encircling the intussusceptum on air enema for intussusception reduction: an
      indication for surgery?
AB  - OBJECTIVES: The prompt identification of children in whom enema reduction of
      intussusception might fail and surgery is necessary is crucial in order to avoid
      futile repeat attempts and untoward complications. The purpose of this
      retrospective review was to determine whether air encircling the intussusceptum
      in the small bowel during air enema for intussusception reduction could serve as
      an indication for operation rather than repeat attempts at radiological
      reduction. METHODS: Imaging studies of 83 children aged 4 to 40 months with
      idiopathic intussusception who had air enema for intussusception reduction were
      reviewed for the presence of air encircling the intussusceptum in the distal
      small bowel. Findings were correlated with clinical course and surgical findings.
      RESULTS: In 12 of 83 patients, air was seen encircling the intussusceptum in the
      small bowel, and in 11 of these (88%) air enema failed to reduce the
      intussusception. In 8 of the 11, delayed repeated attempts using air enema failed
      to reduce intussusception. Clinical signs and their duration did not differ
      between those children without and those with air encircling the intussusceptum.
      CONCLUSION: In the presence of air encircling the intussusceptum in the distal
      small bowel on air enema, delayed repeated attempts for intussusception reduction
      are unlikely to succeed, and surgery is indicated.

PMID- 21081578
TI  - Another fractured neck of femur: do we need a lateral X-ray?
AB  - OBJECTIVE: This study aimed to define the role of the lateral X-ray in the
      assessment and treatment planning of proximal femoral fractures. Occult fractures
      were not included. METHODS: Radiographs from 359 consecutive patients with
      proximal femoral fractures admitted to our emergency department over a 12 month
      period were divided into anteroposterior (AP) views and lateral views. Three
      blinded reviewers independently assessed the radiographs, first AP views alone
      then AP plus lateral views, noting the fracture classification for each
      radiograph. These assessments were then compared with the intra-operative
      diagnosis, which was used as the gold standard. A 2 * 2 contingency square table
      was created and Pearson's chi(2) test was used for statistical analysis. RESULTS:
      The rate of correct classification by the reviewers was improved by the
      assessment of the lateral X-ray in addition to the AP view for intracapsular
      fractures (p<0.013) but not for extracapsular fractures (p=0.27). However, the
      only advantage obtained by assessing the lateral view in intracapsular fractures
      was the detection of displacement where the fracture appeared undisplaced on the
      initial AP view. CONCLUSION: This study provides statistical evidence that one
      view is adequate and safe for the majority of hip fractures. The lateral
      radiograph should not be performed routinely in order to make considerable
      savings in money and time and to avoid unnecessary patient discomfort.

PMID- 21081579
TI  - Comparison of mammography, sonography, MRI and clinical examination in patients
      with locally advanced or inflammatory breast cancer who underwent neoadjuvant
      chemotherapy.
AB  - OBJECTIVES: The purpose of this study was to determine the relative accuracies of
      mammography, sonography, MRI and clinical examination in predicting residual
      tumour size and pathological response after neoadjuvant chemotherapy for locally
      advanced or inflammatory breast cancer. Each prediction method was compared with
      the gold standard of surgical pathology. METHODS: 43 patients (age range, 25-62
      years; mean age, 42.7 years) with locally advanced or inflammatory breast cancer
      who had been treated by neoadjuvant chemotherapy were enrolled prospectively. We
      compared the predicted residual tumour size and the predicted response on imaging
      and clinical examination with residual tumour size and response on pathology.
      Statistical analysis was performed using weighted kappa statistics and intraclass
      correlation coefficients (ICC). RESULTS: The ICC values between predicted tumour
      size and pathologically determined tumour size were 0.65 for clinical
      examination, 0.69 for mammography, 0.78 for sonography and 0.97 for MRI.
      Agreement between the response predictions at mid-treatment and the responses
      measured by pathology had kappa values of 0.28 for clinical examination, 0.32 for
      mammography, 0.46 for sonography and 0.68 for MRI. Agreement between the final
      response predictions and the responses measured by pathology had kappa values of
      0.43 for clinical examination, 0.44 for mammography, 0.50 for sonography and 0.82
      for MRI. CONCLUSION: Predictions of response and residual tumour size made on MRI
      were better correlated with the assessments of response and residual tumour size
      made upon pathology than were predictions made on the basis of clinical
      examination, mammography or sonography. Thus, the evaluation of predicted
      response using MRI could provide a relatively sensitive early assessment of
      chemotherapy efficacy.

PMID- 21081580
TI  - Reduction of motion artefacts in on-board cone beam CT by warping of projection
      images.
AB  - OBJECTIVE: We describe the development and testing of a motion correction method
      for flat panel imager-based cone beam CT (CBCT) based on warping of projection
      images. METHODS: Markers within or on the surface of the patient were tracked and
      their mean three-dimensional (3D) position calculated. The two-dimensional (2D)
      cone beam projection images were then warped before reconstruction to place each
      marker at the projection from its mean 3D position. The motion correction method
      was tested using simulated cone beam projection images of a deforming virtual
      phantom, real CBCT images of a moving breast phantom and clinical CBCT images of
      a patient with breast cancer and another with pancreatic cancer undergoing
      radiotherapy. RESULTS: In phantom studies, the method was shown to greatly reduce
      motion artefacts in the locality of the radiotherapy target and allowed the true
      surface shape to be accurately recovered. The breast phantom motion-compensated
      surface was within 1 mm of the true surface shape for 90% of surface points and
      greater than 2 mm from the true surface at only 2% of points. Clinical CBCT
      images showed improved image quality in the locality of the radiotherapy target
      after motion correction. CONCLUSION: The proposed method is effective in reducing
      motion artefacts in CBCT images.

PMID- 21081581
TI  - Diffusion-weighted imaging of solid or predominantly solid gynaecological
      adnexial masses: is it useful in the differential diagnosis?
AB  - OBJECTIVES: This study investigated whether diffusion-weighted imaging (DWI) and
      apparent diffusion coefficient (ADC) values provide specific information that
      allows the diagnosis of solid or predominantly solid gynaecological adnexial
      lesions, especially whether they can discriminate benign and malignant lesions.
      METHODS: DWI was performed in 37 patients with histologically proven solid or
      predominantly solid adnexial lesions (22 malignant and 15 benign neoplasms). The
      lesions in our data set were divided into two groups, all adnexial lesions or
      lesions of ovarian origin, for evaluation. The areas of the highest signal
      intensity on DWI (b = 800 s mm(-2)) and the lowest ADC values within the lesions
      were evaluated. RESULTS: On DWI, high signal intensity was observed more often in
      malignant than in benign lesions (p<0.0001). There was no significant difference
      between the ADC values of the malignant and benign lesions in either the adnexial
      (0.88+/-0.16 vs 0.84+/-0.42; p = 0.96) or the ovarian (0.85+/-0.14 vs 1.05+/-0.2;
      p = 0.133) lesions. When signal intensities on DWI were compared, however,
      malignant lesions had higher values than the benign lesions in both the adnexial
      (0.69+/-0.21 vs 0.29+/-0.13; p<0.0001) and the ovarian lesions (0.75+/-0.14 vs
      0.37+/-0.24; p = 0.003). CONCLUSION: On DWI, high signal intensity was observed
      more frequently with the malignant lesions.

PMID- 21081582
TI  - 64-Slice multidetector row CT angiography of the abdomen: comparison of low
      versus high concentration iodinated contrast media in a porcine model.
AB  - OBJECTIVE: In this study we aimed to assess the image quality and degree of
      vascular enhancement using low-concentration contrast media (LCCM) (300 mg I ml(
      1)) and high-concentration contrast media (HCCM) (370 mg I ml(-1)) on 64-slice
      multidetector row CT (MDCT) abdominal CT angiography (CTA). In addition, we aimed
      to study the feasibility of using HCCM with a reduced total iodine dose. METHODS:
      CTA of the abdomen on a 64-slice MDCT was performed on 15 anaesthetised pigs.
      Study pigs were divided into three groups of five each based on the iodine
      concentration and dose received: Group A (LCCM; 300 mg I ml(-1)), Group B (HCCM;
      370 mg I ml(-1)) and Group C HCCM with 20% less iodine dose. The total iodine
      injected was kept constant (600 mg kg(-1)) in Groups A and B. Qualitative and
      quantitative analyses were performed to study and compare each group for image
      quality, visibility of the branch order of the superior mesenteric artery (SMA),
      artefacts, degree of enhancement in the aorta and main stem arteries and
      uniformity of enhancement in the aorta. Groups were compared using the analysis
      of variance test. RESULTS: The image quality of 64-slice MDCT angiography was
      excellent with a mean score of 4.63 and confident visualisation of the third to
      fifth order branches of the SMA in all groups. Group B demonstrated superior
      vascular enhancement, as compared with Groups A and C (p<=0.05). Uniform aortic
      enhancement was achieved with the use of LCCM and HCCM with 20% less iodine dose.
      CONCLUSION: 64-slice MDCT angiography of the abdomen was of excellent quality.
      HCCM improves contrast enhancement and overall CTA image quality and allows the
      iodine dose to be reduced.

PMID- 21081583
TI  - CT colonography: computer-assisted detection of colorectal cancer.
AB  - OBJECTIVES: Computer-aided detection (CAD) for CT colonography (CTC) has been
      developed to detect benign polyps in asymptomatic patients. We aimed to determine
      whether such a CAD system can also detect cancer in symptomatic patients.
      METHODS: CTC data from 137 symptomatic patients subsequently proven to have
      colorectal cancer were analysed by a CAD system at 4 different sphericity
      settings: 0, 50, 75 and 100. CAD prompts were classified by an observer as either
      true-positive if overlapping a cancer or false-positive if elsewhere.
      Colonoscopic data were used to aid matching. RESULTS: Of 137 cancers, CAD
      identified 124 (90.5%), 122 (89.1%), 119 (86.9%) and 102 (74.5%) at a sphericity
      of 0, 50, 75 and 100, respectively. A substantial proportion of cancers were
      detected on either the prone or supine acquisition alone. Of 125 patients with
      prone and supine acquisitions, 39.3%, 38.3%, 43.2% and 50.5% of cancers were
      detected on a single acquisition at a sphericity of 0, 50, 75 and 100,
      respectively. CAD detected three cancers missed by radiologists at the original
      clinical interpretation. False-positive prompts decreased with increasing
      sphericity value (median 65, 57, 45, 24 per patient at values of 0, 50, 75, 100,
      respectively) but many patients were poorly prepared. CONCLUSION: CAD can detect
      symptomatic colorectal cancer but must be applied to both prone and supine
      acquisitions for best performance.

PMID- 21081584
TI  - CT differentiation of pyogenic liver abscesses caused by Klebsiella pneumoniae vs
      non-Klebsiella pneumoniae.
AB  - OBJECTIVE: Klebsiella pneumoniae is one of the organisms most commonly isolated
      from pyogenic liver abscesses in Asian populations. We compared CT findings in
      liver abscesses caused by K. pneumoniae with those caused by other bacterial
      pathogens. METHODS: Of 214 patients with liver abscesses examined over a 5 year
      period, 129 patients with positive blood or aspirate cultures were enrolled. The
      patients were divided into two groups: the K. pneumoniae monomicrobial liver
      abscess (KLA) group (n = 59) and the non-K. pneumoniae monomicrobial or
      polymicrobial liver abscess (non-KLA) group (n = 70). Two radiologists blinded to
      the culture results evaluated the CT images, recording the number, size, location
      and configuration of abscesses, the thickness of the abscess wall, the pattern of
      rim enhancement, septal enhancement, the double target sign, internal necrotic
      debris, internal gas bubbles and underlying biliary disease. The presence of
      diabetes and metastatic infection was also compared between groups. Statistical
      analyses were performed using univariate (Student's t-test and chi(2) test) and
      multivariate analyses. RESULTS: Multivariate analysis showed that a thin wall,
      necrotic debris, metastatic infection and the absence of underlying biliary
      disease were the most significant predictors of KLA. When three of the four
      criteria were used in combination, a specificity of 98.6% was achieved for the
      diagnosis of KLA. CONCLUSION: A thin-walled abscess, internal necrotic debris,
      the presence of metastatic infection and the absence of underlying biliary
      disease may be useful CT findings in the early diagnosis of K. pneumoniae liver
      abscesses.

PMID- 21081585
TI  - Seeds of alpine plants are short lived: implications for long-term conservation.
AB  - BACKGROUND AND AIMS: Alpine plants are considered one of the groups of species
      most sensitive to the direct and indirect threats to ecosystems caused by land
      use and climate change. Collecting and banking seeds of plant species is
      recognized as an effective tool for providing propagating material to re
      establish wild plant populations and for habitat repair. However, seeds from cold
      wet environments have been shown to be relatively short lived in storage, and
      therefore successful long-term seed conservation for alpine plants may be
      difficult. Here, the life spans of 69 seed lots representing 63 related species
      from alpine and lowland locations from northern Italy are compared. METHODS:
      Seeds were placed into experimental storage at 45  degrees C and 60 % relative
      humidity (RH) and regularly sampled for germination. The time taken in storage
      for viability to fall to 50 % (p(50)) was determined using probit analysis and
      used as a measure of relative seed longevity between seed lots. KEY RESULTS:
      Across species, p(50) at 45  degrees C and 60 % RH varied from 4.7 to 95.5 d.
      Seed lots from alpine populations/species had significantly lower p(50) values
      compared with those from lowland populations/species; the lowland seed lots
      showed a slower rate of loss of germinability, higher initial seed viability, or
      both. Seeds were progressively longer lived with increased temperature and
      decreased rainfall at the collecting site. CONCLUSIONS: Seeds of alpine plants
      are short lived in storage compared with those from lowland populations/related
      taxa. The lower resistance to ageing in seeds of alpine plants may arise from low
      selection pressure for seed resistance to ageing and/or damage incurred during
      seed development due to the cool wet conditions of the alpine climate. Long-term
      seed conservation of several alpine species using conventional seed banking
      methods will be problematic.

PMID- 21081586
TI  - Actual causes of death in Chaoyang District of Beijing, China, 2007.
AB  - OBJECTIVES: To identify and quantify major external (non-genetic) factors that
      contribute to death in Chaoyang District of Beijing, China in 2007. METHODS: The
      death registration data reported to the Center of Disease Control and Prevention
      of Chaoyang District of Beijing, China, during the year 2007, were obtained. The
      analysis was conducted in 2009 using the health risk factors identified by the
      World Health Report 2002 and the population attributable fractions of mortality
      from Global burden of disease and risk factors. The estimates of actual causes of
      death attributable to each risk factor were calculated by multiplying the
      population attributable fractions of mortality by the corresponding number of
      deaths of the subgroup or total population. RESULTS: The five leading actual
      causes of death in Chaoyang District of Beijing, China in 2007 were high blood
      pressure (2159 deaths, 18%), smoking (990, 8%), low fruit and vegetable
      consumption (968, 8%), high cholesterol (891, 7%), and physical inactivity (629,
      5%). The pattern and ordering of these leading causes vary with sex and age
      specific subgroups. CONCLUSIONS: More than half of the total number of deaths in
      Chaoyang District in 2007 could be attributed to a few major preventable risk
      factors. Although the study focused on only one district of Beijing in one single
      year, and is by no means comprehensive, its findings suggest that public health
      policies and programmes in China should address these public health concerns by
      focusing on these largely preventable risk factors for primary prevention.

PMID- 21081587
TI  - Endocrine problems in pregnancy.
AB  - This paper aims to describe the pathophysiology and management of the main
      endocrine complications of pregnancy. For each endocrine dysfunction, the issues
      with the fetus, the mother, obstetric complications, and the long term prognosis
      for the disease itself need to be considered. Key management issues are
      highlighted with each condition. Thyroid dysfunction and goitre are common while
      management is relatively straightforward. Adrenal, pituitary, and parathyroid
      diseases present less commonly in pregnancy. Early recognition of endocrine
      disease in pregnancy and appropriate management has the potential to improve
      outcome for the mother and fetus in the short and long term.

PMID- 21081588
TI  - The Gerontologist.

PMID- 21081590
TI  - MRSA screening on a paediatric intensive care unit.
AB  - The accuracies of chromogenic agar and the GeneXpert real-time PCR system
      (Cepheid, Sunnyvale, California, USA) for admission methicillin-resistant
      Staphylococcus aureus (MRSA) screening of 1336 consecutive paediatric intensive
      care unit patients (1282 evaluable swab results) were determined using enrichment
      culture as the reference standard. Twenty (1.6%) swabs were MRSA-positive by
      enrichment culture (reference test). PCR was more sensitive (0.9, 95% CI 0.68 to
      0.99 vs 0.65, 95% CI 0.41 to 0.85) but less specific (0.98, 95% CI 0.98 to 0.99
      vs 100%) than chromogenic agar. After introduction of screening no patient
      developed MRSA infection or acquired MRSA after admission. In the preceding 3
      years of screening, 16 patients had MRSA diagnosed after admission, nine
      presenting with infection. The accuracy of PCR was comparable to previous
      studies, but the positive predictive value in a low prevalence paediatric
      population was only 0.49. Screening provided some clinical benefits, to which the
      early availability of PCR results may have contributed.

PMID- 21081591
TI  - Maternal methadone therapy increases QTc interval in newborn infants.
AB  - INTRODUCTION: Prolongation of the QT interval is a risk factor for sudden death.
      Methadone treatment is a well-recognised cause of QT interval lengthening in
      adults. The effect of maternal methadone treatment on the QT interval of the
      newborn infant is not known. This is the first prospective study of corrected QT
      (QTc) interval in infants born to mothers receiving methadone. AIM: To compare
      QTc interval in infants born to mothers receiving methadone therapy with healthy
      controls. METHOD: Twenty-six term infants (median gestation 38 weeks, range 37
      40) born to mothers on methadone therapy had ECG recordings on days 1, 2, 4 and
      7. The QTc interval was calculated using the Bazzett formula. Results for days 1
      and 2 were compared with healthy matched control infants born to mothers who were
      not receiving methadone. Results for days 4 and 7 were compared with published
      normal values. RESULTS: In the methadone group, the QTc interval was
      significantly prolonged on days 1 and 2 of life. On days 4 and 7, this increase
      was no longer present. None of the infants in either group had any evidence of
      significant cardiac rhythm disturbance. CONCLUSION: Maternal methadone therapy
      can cause transient prolongation of the QTc interval in newborn infants in the
      first 2 days of life. Newborns exposed to methadone are at risk of cardiac rhythm
      disturbances. Bradycardia, tachycardia or an irregular heart rate in an infant
      born to a mother on methadone treatment should prompt investigation with a 12
      lead ECG.

PMID- 21081589
TI  - Does maternal feeding restriction lead to childhood obesity in a prospective
      cohort study?
AB  - BACKGROUND: Some studies show that greater parental control over children's
      eating habits predicts later obesity, but it is unclear whether parents are
      reacting to infants who are already overweight. OBJECTIVE: To examine the
      longitudinal association between maternal feeding restriction at age 1 and body
      mass index (BMI) at age 3 and the extent to which the association is explained by
      weight for length (WFL) at age 1. METHODS: We studied 837 mother-infant pairs
      from a prospective cohort study. The main exposure was maternal feeding
      restriction at age 1, defined as agreeing or strongly agreeing with the following
      question: "I have to be careful not to feed my child too much." We ran
      multivariable linear regression models before and after adjusting for WFL at age
      1. All models were adjusted for parental and child sociodemographic
      characteristics. RESULTS: 100 (12.0%) mothers reported feeding restriction at age
      1. Mean (SD) WFL z-score at age 1 was 0.32 (1.01), and BMI z-score at age 3 was
      0.43 (1.01). Maternal feeding restriction at age 1 was associated with higher BMI
      z-score at age 3 before (beta 0.26 (95% CI 0.05 to 0.48)) but not after (beta
      0.00 (95% CI -0.17 to 0.18)) adjusting for WFL z-score at age 1. Each unit of WFL
      z-score at age 1 was associated with an increment of 0.57 BMI z-score units at
      age 3 (95% CI 0.51 to 0.62). CONCLUSIONS: We found that maternal feeding
      restriction was associated with children having a higher BMI at age 3 before, but
      not after, adjusting for WFL at age 1. One potential reason may be that parents
      restrict the food intake of infants who are already overweight.

PMID- 21081592
TI  - Lactobezoar--not so bizarre!

PMID- 21081593
TI  - Airway obstruction and gas leak during mask ventilation of preterm infants in the
      delivery room.
AB  - INTRODUCTION: Preterm infants with inadequate breathing receive positive pressure
      ventilation (PPV) by mask with variable success. The authors examined recordings
      of PPV given to preterm infants in the delivery room for prevalence of mask leak
      and airway obstruction. METHODS AND PATIENTS: The authors reviewed recordings of
      infants at <32 weeks' gestation born between February 2006 and March 2009. PPV
      was delivered with a T-piece or self-inflating bag and a round silicone face
      mask. Airway pressures and gas flow were recorded with a respiratory function
      monitor (RFM). Videos recorded from a web camera were used to review the
      resuscitation. The first 2 min of PPV were analysed for each infant. Obstruction
      was arbitrarily defined as a 75% reduction in delivered expired tidal volume
      (V(Te)) and significant face-mask leak as >75%. RESULTS: The authors analysed
      recordings of 56 preterm infants. Obstruction occurred in 14 (26%) recordings and
      leaks in 27 (51%). Both obstruction and mask leaks were seen in eight (14%)
      recordings, and neither was seen in 15 (27%). Obstruction occurred at a median
      (IQR) of 48 (24-60) s after the start of PPV. A median (range) of 22 (3-83)
      consecutive obstructed inflations were delivered. Face-mask leaks occurred from
      the first inflation in 19/27 (70%) and in the remaining eight at a median (IQR)
      of 30 (24-46) s after the start of PPV. A median (range) of 10 (3-117)
      consecutive inflations with a leak >75% were delivered. CONCLUSION: Airway
      obstruction and face-mask leak are common during the first 2 min of PPV. An RFM
      enables detection of important airway obstruction and mask leak.

PMID- 21081594
TI  - Survey of nasal continuous positive airways pressure (NCPAP) and nasal
      intermittent positive pressure ventilation (NIPPV) use in Irish newborn
      nurseries.

PMID- 21081596
TI  - Doc, my knees give way!

PMID- 21081595
TI  - Adoption, non-adoption, and abandonment of a personal electronic health record:
      case study of HealthSpace.
AB  - OBJECTIVE: To evaluate the policy making process, implementation by NHS
      organisations, and patients' and carers' experiences of efforts to introduce an
      internet accessible personal electronic health record (HealthSpace) in a public
      sector healthcare system. DESIGN: Mixed method, multilevel case study. SETTING:
      English National Health Service; the basic HealthSpace technology (available
      throughout England) and the advanced version (available in a few localities where
      this option had been introduced) were considered. MAIN OUTCOME MEASURES: National
      statistics on invitations sent, HealthSpace accounts created, and interviews and
      ethnographic observation of patients and carers. Data analysis was informed by a
      socio-technical approach which considered macro and micro influences on both
      adoption and non-adoption of innovations, and by the principles of critical
      discourse analysis. PARTICIPANTS: 56 patients and carers (of whom 21 opened a
      basic HealthSpace account, 20 had diabetes but were not initially using
      HealthSpace, and 15 used advanced HealthSpace accounts to exchange messages with
      their general practitioner), 3000 pages of documents (policies, strategies,
      business plans, minutes of meetings, correspondence), observational field notes,
      and 160 interviews with policy makers, project managers, and clinical staff.
      RESULTS: Between 2007 and October 2010, 172 950 people opened a basic HealthSpace
      account. 2913 (0.13% of those invited) opened an advanced account, compared with
      5-10% of the population anticipated in the original business case. Overall,
      patients perceived HealthSpace as neither useful nor easy to use and its
      functionality aligned poorly with their expectations and self management
      practices. Those who used email-style messaging were positive about its benefits,
      but enthusiasm beyond three early adopter clinicians was low, and fewer than 100
      of 30 000 patients expressed interest. Policy makers' hopes that "deploying"
      HealthSpace would lead to empowered patients, personalised care, lower NHS costs,
      better data quality, and improved health literacy were not realised over the
      three year evaluation period. CONCLUSION: Unless personal electronic health
      records align closely with people's attitudes, self management practices,
      identified information needs, and the wider care package (including
      organisational routines and incentive structures for clinicians), the risk that
      they will be abandoned or not adopted at all is substantial. Conceptualising such
      records dynamically (as components of a socio-technical network) rather than
      statically (as containers for data) and employing user centred design techniques
      might improve their chances of adoption and use. The findings raise questions
      about how eHealth programmes in England are developed and approved at policy
      level.

PMID- 21081597
TI  - The problem of orphan drugs.

PMID- 21081598
TI  - Orphan drug pricing may warrant a competition law investigation.

PMID- 21081599
TI  - Open letter to prime minister David Cameron and health secretary Andrew Lansley.

PMID- 21081601
TI  - Planning a consultant delivered NHS.

PMID- 21081600
TI  - Effect on peer review of telling reviewers that their signed reviews might be
      posted on the web: randomised controlled trial.
AB  - OBJECTIVES: To see whether telling peer reviewers that their signed reviews of
      original research papers might be posted on the BMJ's website would affect the
      quality of their reviews. DESIGN: Randomised controlled trial. SETTING: A large
      international general medical journal based in the United Kingdom. PARTICIPANTS:
      541 authors, 471 peer reviewers, and 12 editors. INTERVENTION: Consecutive
      eligible papers were randomised either to have the reviewer's signed report made
      available on the BMJ's website alongside the published paper (intervention group)
      or to have the report made available only to the author-the BMJ's normal
      procedure (control group). The intervention was the act of revealing to reviewers
      after they had agreed to review but before they undertook their review-that their
      signed report might appear on the website. MAIN OUTCOME MEASURES: The main
      outcome measure was the quality of the reviews, as independently rated on a scale
      of 1 to 5 using a validated instrument by two editors and the corresponding
      author. Authors and editors were blind to the intervention group. Authors rated
      review quality before the fate of their paper had been decided. Additional
      outcomes were the time taken to complete the review and the reviewer's
      recommendation regarding publication. RESULTS: 558 manuscripts were randomised,
      and 471 manuscripts remained after exclusions. Of the 1039 reviewers approached
      to take part in the study, 568 (55%) declined. Two editors' evaluations of the
      quality of the peer review were obtained for all 471 manuscripts, with the
      corresponding author's evaluation obtained for 453. There was no significant
      difference in review quality between the intervention and control groups (mean
      difference for editors 0.04, 95% CI -0.09 to 0.17; for authors 0.06, 95% CI -0.09
      to 0.20). Any possible difference in favour of the control group was well below
      the level regarded as editorially significant. Reviewers in the intervention
      group took significantly longer to review (mean difference 25 minutes, 95% CI 3.0
      to 47.0 minutes). CONCLUSION: Telling peer reviewers that their signed reviews
      might be available in the public domain on the BMJ's website had no important
      effect on review quality. Although the possibility of posting reviews online was
      associated with a high refusal rate among potential peer reviewers and an
      increase in the amount of time taken to write a review, we believe that the
      ethical arguments in favour of open peer review more than outweigh these
      disadvantages.

PMID- 21081602
TI  - Is open peer review the fairest system? Yes.

PMID- 21081603
TI  - Is open peer review the fairest system? No.

PMID- 21081604
TI  - FDA breached integrity over investigation of contaminated heparin.

PMID- 21081607
TI  - What makes an orphan drug?

PMID- 21081608
TI  - Estimating HIV prevalence. A cautious note on household surveys in poor settings.

PMID- 21081609
TI  - Alzheimer's disease/syndrome?. There are two types of disease.

PMID- 21081610
TI  - Data openness. Reporting of absolute risk.

PMID- 21081611
TI  - Data openness. Absolute v relative risk reduction.

PMID- 21081612
TI  - Data openness. Independent public inquiries needed to ensure drug safety.

PMID- 21081613
TI  - Reboxetine in depression. NICE guidance differs, so where next?

PMID- 21081614
TI  - Reboxetine in depression. All the relevant data?

PMID- 21081615
TI  - Errors in prescribing. Spell and write out numbers.

PMID- 21081616
TI  - Errors in prescribing. Reducing insulin errors.

PMID- 21081617
TI  - Errors in prescribing. Hypervigilance is needed.

PMID- 21081618
TI  - Heeding lessons from Shipman. Attention has been distracted.

PMID- 21081619
TI  - Heeding lessons from Shipman. Premise is wrongheaded.

PMID- 21081620
TI  - Request for breast reduction. Don't forget chronic scar pain.

PMID- 21081621
TI  - Not every child with diabetes needs insulin.

PMID- 21081623
TI  - Stroke patients take part in "milestone" UK trial of stem cell therapy.

PMID- 21081625
TI  - Low-dose rosiglitazone plus metformin reduces risk of incident type 2 diabetes
      compared with placebo in people with impaired glucose tolerance.

PMID- 21081626
TI  - The additional value of self-monitoring of blood glucose in patients with type 2
      diabetes not using insulin is 'not proven'.

PMID- 21081627
TI  - Large placebo-controlled RCT in myocardial infarction survivors finds that daily
      folic acid and vitamin B12 have no effect on risk of major vascular event.

PMID- 21081628
TI  - Prognostic value of CRP in stable coronary artery disease unclear due to a
      variety of biases in existing studies, therefore no clinical practice
      recommendations can be made.

PMID- 21081629
TI  - Pregabalin is more effective than placebo for restless legs syndrome with mild
      adverse effects of daytime somnolence, headache and unsteadiness.

PMID- 21081630
TI  - Proton pump inhibitors given before endoscopy for upper gastrointestinal bleeding
      do not improve survival, rebleeding or need for surgery.

PMID- 21081638
TI  - Automated external defibrillator use at NCAA Division II and III universities.
AB  - OBJECTIVE: The placement of automated external defibrillators (AEDs) at
      collegiate sporting venues is a growing trend. The purpose of this study was to
      investigate the prevalence, location and past utilisation of AEDs at National
      Collegiate Athletic Association (NCAA) Division II and III universities. DESIGN:
      Cross-sectional survey. SETTING: NCAA Division II and III universities.
      PARTICIPANTS: Questionnaires were mailed to the head athletic trainer at NCAA
      Division II and III (N=711) colleges and universities in the fall of 2003.
      Findings were compared to previously published results at Division I
      institutions. MAIN OUTCOME MEASURE: Prevalence, location and past utilisation of
      AEDs. RESULTS: Completed surveys were returned by 254 NCAA Division II and III
      institutions for a 35.7% response rate (254/711). 205 (81%) institutions had at
      least one AED in the university athletic setting, with a median of 2 AEDs per
      institution (range 1-9). Athletic training rooms (75%) were the most likely
      location to place an AED. Twelve cases of AED use for sudden cardiac arrest were
      reported with 67% (8/12) occurring in older non-students, 16% (2/12) in
      intercollegiate athletes and 16% (2/12) in students (non-intercollegiate
      athletes). The AED deployed a shock in eight cases. 8 of 12 (66%) victims were
      immediately resuscitated, but only 4 survived to hospital discharge (overall
      survival 33%). None of the intercollegiate athletes or students survived.
      CONCLUSIONS: Most NCAA Division II and III institutions that responded to the
      survey have implemented AEDs in their athletic programs, although they have a
      lower prevalence of AEDs than previously reported at Division I universities.
      Although no benefit was demonstrated in a small number of intercollegiate
      athletes, AEDs were successfully used in older individuals on campus with cardiac
      arrest.

PMID- 21081639
TI  - Spreading the word on sports concussion: citation analysis of summary and
      agreement, position and consensus statements on sports concussion.
AB  - BACKGROUND: the growing concern over concussion in sports has led to the
      publication of five major summary and agreement, position and consensus
      statements since 2000. The dissemination of information from these statements is
      largely unknown and difficult to quantify, but their impact on the research
      community can be quantified by analysing the number of citations to these key
      publications. The purpose of this review is to report the number and pattern of
      citations to the key published statements on sports concussion. METHODS: Web of
      Science, Scopus and PubMed were searched from 2000 to mid-December 2009 using two
      different search strategies. The first strategy used the search terms
      'concussion' and 'first author' of the statement article, while the second used
      the 'title' of the target article as the key search term. RESULTS: the
      publications resulting from the three 'Concussion in Sport' (CIS) group
      conferences were cited by 532 journal articles, while the National Athletic
      Trainers' Association position statement was cited 123 times. The highest number
      of citations to each of the five identified statements was seen in 2009. British
      Journal of Sports Medicine was the most frequently cited journal. CONCLUSION: the
      citation analysis of the key statements on sports concussion has shown that the
      target papers have been widely cited in the research literature, with the highest
      number of citations being from the publications arising from the CIS group
      conferences. The authors have shown their preference to cite source articles
      published in the British Journal of Sports Medicine.

PMID- 21081640
TI  - New method to identify athletes at high risk of ACL injury using clinic-based
      measurements and freeware computer analysis.
AB  - BACKGROUND: High knee abduction moment (KAM) landing mechanics, measured in the
      biomechanics laboratory, can successfully identify female athletes at increased
      risk for anterior cruciate ligament (ACL) injury. METHODS: The authors validated
      a simpler, clinic-based ACL injury prediction algorithm to identify female
      athletes with high KAM measures. The validated ACL injury prediction algorithm
      employs the clinically obtainable measures of knee valgus motion, knee flexion
      range of motion, body mass, tibia length and quadriceps-to-hamstrings ratio. It
      predicts high KAMs in female athletes with high sensitivity (77%) and specificity
      (71%). CONCLUSION: This report outlines the techniques for this ACL injury
      prediction algorithm using clinic-based measurements and computer analyses that
      require only freely available public domain software.

PMID- 21081641
TI  - Cost-effectiveness of exercise on prescription with telephone support among women
      in general practice over 2 years.
AB  - AIM: To assess the cost-effectiveness of exercise on prescription with ongoing
      support in general practice. METHODS: Prospective cost-effectiveness study
      undertaken as part of the 2-year Women's lifestyle study randomised controlled
      trial involving 1089 'less-active' women aged 40-74. The 'enhanced Green
      Prescription' intervention included written exercise prescription and brief
      advice from a primary care nurse, face-to-face follow-up at 6 months, and 9
      months of telephone support. The primary outcome was incremental cost of moving
      one 'less-active' person into the 'active' category over 24 months. Direct costs
      of programme delivery were recorded. Other (indirect) costs covered in the
      analyses included participant costs of exercise, costs of primary and secondary
      healthcare utilisation, allied health therapies and time off work (lost
      productivity). Cost-effectiveness ratios were calculated with and without
      including indirect costs. RESULTS: Follow-up rates were 93% at 12 months and 89%
      at 24 months. Significant improvements in physical activity were found at 12 and
      24 months (p<0.01). The exercise programme cost was New Zealand dollars (NZ$)
      93.68 (?45.90) per participant. There was no significant difference in indirect
      costs over the course of the trial between the two groups (rate ratios: 0.99 (95%
      CI 0.81 to 1.2) at 12 months and 1.01 (95% CI 0.83 to 1.23) at 24 months, p=0.9).
      Cost-effectiveness ratios using programme costs were NZ$687 (?331) per person
      made 'active' and sustained at 12 months and NZ$1407 (?678) per person made
      'active' and sustained at 24 months. CONCLUSIONS: This nurse-delivered programme
      with ongoing support is very cost-effective and compares favourably with other
      primary care and community-based physical activity interventions internationally.

PMID- 21081642
TI  - Greater peak rearfoot eversion predicts foot orthoses efficacy in individuals
      with patellofemoral pain syndrome.
AB  - OBJECTIVE: There is growing evidence for the provision of foot orthoses when
      treating individuals with patellofemoral pain syndrome (PFPS), and prescription
      is frequently based on the assessment of foot posture/function. However,
      evaluation of the link between abnormal foot posture/function and foot orthoses
      outcomes has previously been limited to static alignment measures and has
      produced inconsistent findings. In this study, the ability of baseline foot
      kinematics associated with pronation to predict marked improvement 12 weeks
      following foot orthoses prescription in individuals with PFPS was evaluated.
      METHODS: 26 individuals with PFPS were issued with prefabricated foot orthoses,
      and patient-reported level of improvement was documented at 12 weeks. Potential
      predictors of marked improvement at 12 weeks were measured during walking at
      baseline and included forefoot dorsiflexion and abduction, and rearfoot eversion.
      RESULTS: Of the 25 participants who completed the study, seven (28%) reported
      marked improvement with the foot orthoses after 12 weeks. Discriminant function
      analysis revealed a greater peak rearfoot eversion to be the only significant
      independent predictor of marked improvement. CONCLUSION: These findings provide
      preliminary evidence that greater peak rearfoot eversion is predictive of marked
      improvement 12 weeks following prefabricated foot orthoses prescription in
      individuals with PFPS. Therefore, foot orthoses may be most effective in the
      subgroup of people with PFPS and increased dynamic foot pronation.

PMID- 21081643
TI  - Dr Runge: a German pioneer in sclerosing therapy in epicondylitis in 1873.

PMID- 21081644
TI  - Progesterone receptor membrane component 1 inhibits the activity of drug
      metabolizing cytochromes P450 and binds to cytochrome P450 reductase.
AB  - Progesterone receptor membrane component 1 (PGRMC1) has been shown to interact
      with several cytochromes P450 (P450s) and to activate enzymatic activity of P450s
      involved in sterol biosynthesis. We analyzed the interactions of PGRMC1 with the
      drug-metabolizing P450s, CYP2C2, CYP2C8, and CYP3A4, in transfected cells. Based
      on coimmunoprecipitation assays, PGRMC1 bound efficiently to all three P450s, and
      binding to the catalytic cytoplasmic domain of CYP2C2 was much more efficient
      than to a chimera containing only the N-terminal transmembrane domain. Down
      regulation of PGRMC1 expression levels in human embryonic kidney 293 and HepG2
      cell lines stably expressing PGRMC1-specific small interfering RNA had no effect
      on the endoplasmic reticulum localization and expression levels of P450s, whereas
      enzymatic activities of CYP2C2, CYP2C8, and CYP3A4 were slightly higher in PGRMC1
      deficient cells. Cotransfection of cells with P450s and PGRMC1 resulted in PGRMC1
      concentration-dependent inhibition of the P450 activities, and this inhibition
      was partially reversed by increased expression of the P450 reductase (CPR). In
      contrast, CYP51 activity was decreased by down-regulation of PGRMC1 and
      expression of PGRMC1 in the PGRMC1-deficient cells increased CYP51 activity. In
      cells cotransfected with CPR and PGRMC1, strong binding of CPR to PGRMC1 was
      observed; however, in the presence of CYP2C2, interaction of PGRMC1 with CPR was
      significantly reduced, suggesting that CYP2C2 competes with CPR for binding to
      PGRMC1. These data show that in contrast to sterol synthesizing P450, PGRMC1 is
      not required for the activities of several drug-metabolizing P450s, and its
      overexpression inhibits those P450 activities. Furthermore, PGRMC1 binds to CPR,
      which may influence P450 activity.

PMID- 21081645
TI  - A structural insight into the reorientation of transmembrane domains 3 and 5
      during family A G protein-coupled receptor activation.
AB  - Rearrangement of transmembrane domains (TMs) 3 and 5 after agonist binding is
      necessary for stabilization of the active state of class A G protein-coupled
      receptors (GPCRs). Using site-directed mutagenesis and functional assays, we
      provide the first evidence that the TAS(I/V) sequence motif at positions 3.37 to
      3.40, highly conserved in aminergic receptors, plays a key role in the activation
      of the histamine H1 receptor. By combining these data with structural information
      from X-ray crystallography and computational modeling, we suggest that Thr(3.37)
      interacts with TM5, stabilizing the inactive state of the receptor, whereas the
      hydrophobic side chain at position 3.40, highly conserved in the whole class A
      GPCR family, facilitates the reorientation of TM5. We propose that the structural
      change of TM5 during the process of GPCR activation involves a local Pro(5.50)
      induced unwinding of the helix, acting as a hinge, and the highly conserved
      hydrophobic Ile(3.40) side chain, acting as a pivot.

PMID- 21081646
TI  - Absolute humidity and pandemic versus epidemic influenza.
AB  - Experimental and epidemiologic evidence indicates that variations of absolute
      humidity account for the onset and seasonal cycle of epidemic influenza in
      temperate regions. A role for absolute humidity in the transmission of pandemic
      influenza, such as 2009 A/H1N1, has yet to be demonstrated and, indeed, outbreaks
      of pandemic influenza during more humid spring, summer, and autumn months might
      appear to constitute evidence against an effect of humidity. However, here the
      authors show that variations of the basic and effective reproductive numbers for
      influenza, caused by seasonal changes in absolute humidity, are consistent with
      the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in
      temperate regions, as well as wintertime transmission of epidemic influenza.
      Indeed, absolute humidity conditions correctly identify the region of the United
      States vulnerable to a third, wintertime wave of pandemic influenza. These
      findings suggest that the timing of pandemic influenza outbreaks is controlled by
      a combination of absolute humidity conditions, levels of susceptibility, and
      changes in population-mixing and contact rates.

PMID- 21081647
TI  - CEACAM1: a key regulator of vascular permeability.
AB  - Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) is an immunoglobulin
      like cell surface co-receptor expressed on epithelial, hematopoietic and
      endothelial cells. CEACAM1 functions as an adhesion molecule, mainly binding to
      itself or other members of the CEA family. We and others have previously shown
      that CEACAM1 is crucial for in vivo vascular integrity during ischemic neo
      vascularization. Here, we have deciphered the roles of CEACAM1 in normal and
      pathological vascularization. We have found that Ceacam1-/- mice exhibit a
      significant increase in basal vascular permeability related to increased basal
      Akt and endothelial nitric oxide synthase (eNOS) activation in primary murine
      lung endothelial cells (MLECs). Moreover, CEACAM1 deletion in MLECs inhibits VEGF
      mediated nitric oxide (NO) production, consistent with defective VEGF-dependent
      in vivo permeability in Ceacam1-/- mice. In addition, Ceacam1-null mice exhibit
      increased permeability of tumor vasculature. Finally, we demonstrate that CEACAM1
      is tyrosine-phosphorylated upon VEGF treatment in a SHP-1- and Src-dependent
      manner, and that the key residues of the long cytoplasmic domain of CEACAM1 are
      crucial for CEACAM1 phosphorylation and NO production. This data represents the
      first report, to our knowledge, of a functional link between CEACAM1 and the
      VEGFR2/Akt/eNOS-mediated vascular permeability pathway.

PMID- 21081648
TI  - IKK(alpha) controls canonical TGF(beta)-SMAD signaling to regulate genes
      expressing SNAIL and SLUG during EMT in panc1 cells.
AB  - The epithelial to mesenchymal transition (EMT) is a crucial step in tumor
      progression, and the TGFbeta-SMAD signaling pathway is an inductor of EMT in many
      tumor types. One hallmark of EMT is downregulation of the adherens junction
      protein E-cadherin, a process mediated by transcription factors such as the zinc
      fingers SNAIL and SLUG. Here, we report that the catalytic IkappaB kinase (IKK)
      subunit IKKalpha is necessary for the silencing of E-cadherin in a Panc1 cell
      model of TGFbeta-SMAD-mediated EMT, independently of NFkappaB. IKKalpha regulates
      canonical TGFbeta-SMAD signaling by interacting with SMAD3 and controlling SMAD
      complex formation on DNA. Furthermore, we demonstrate that the TGFbeta-IKKalpha
      SMAD signaling pathway induces transcription of the genes encoding SNAIL and
      SLUG. In addition, we demonstrate that IKKalpha also modulates canonical TGFbeta
      SMAD signaling in human MDA-MB231 breast cancer cells, arguing for a more general
      impact of IKKalpha on the control of TGFbeta-SMAD signaling. Taken together,
      these findings indicate that IKKalpha contributes to the tumor-promoting function
      of the TGFbeta-SMAD signaling pathway in particular cancers.

PMID- 21081649
TI  - SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65
      Lys310.
AB  - NF-kappaB regulates the expression of a large number of target genes involved in
      the immune and inflammatory response, apoptosis, cell proliferation,
      differentiation and survival. In this study, we identified SIRT2 as a deacetylase
      of the transcription factor p65. SIRT2 is a member of the family of sirtuins,
      which are NAD(+)-dependent deacetylases involved in several cellular processes.
      SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in
      vivo at Lys310. Moreover, p65 is hyperacetylated at Lys310 in Sirt2(-/-) cells
      after TNFalpha stimulation, which results in the increase in expression of a
      subset of p65 acetylation-dependent target genes. Our work provides evidence that
      p65 is deacetylated by SIRT2 in the cytoplasm to regulate the expression of
      specific NF-kappaB-dependent genes.

PMID- 21081650
TI  - PI3KC2alpha, a class II PI3K, is required for dynamin-independent internalization
      pathways.
AB  - Increasing evidence indicates that cellular uptake of several molecules can occur
      independently of functional dynamin, but the molecular players that regulate
      dynamin-independent endocytosis and the subsequent trafficking steps are still
      largely unknown. A survival-based short-hairpin (sh) RNA screen using a cell line
      expressing a diphtheria toxin receptor (DTR, officially known as HBEGF) anchored
      to GPI (DTR-GPI), which internalizes diphtheria toxin (DT, officially known as
      DTX) in a dynamin-independent manner, identified PI3KC2alpha, a class II
      phosphoinositide 3-kinase (PI3K), as a specific regulator of dynamin-independent
      DT internalization. We found that the internalization of several proteins that
      enter the cell through dynamin-independent pathways led to a relocalization of
      PI3KC2alpha to cargo-positive vesicles. Furthermore, downregulation of
      PI3KC2alpha impaired internalization of CD59 as well as fluid-phase endocytosis.
      Our data suggest a general role for PI3KC2alpha in regulating physiologically
      relevant dynamin-independent internalization pathways by recruiting early
      endosome antigen 1 (EEA1) to vesicular compartments, a step required for the
      intracellular trafficking of vesicles generated by dynamin-independent endocytic
      pathways.

PMID- 21081651
TI  - Uptake and partitioning of amino acids and peptides.
AB  - Plant growth, productivity, and seed yield depend on the efficient uptake,
      metabolism, and allocation of nutrients. Nitrogen is an essential macronutrient
      needed in high amounts. Plants have evolved efficient and selective transport
      systems for nitrogen uptake and transport within the plant to sustain
      development, growth, and finally reproduction. This review summarizes current
      knowledge on membrane proteins involved in transport of amino acids and peptides.
      A special emphasis was put on their function in planta. We focus on uptake of the
      organic nitrogen by the root, source-sink partitioning, and import into floral
      tissues and seeds.

PMID- 21081652
TI  - Spatial sap flow and xylem anatomical characteristics in olive trees under
      different irrigation regimes.
AB  - The compensation heat pulse (CHP) method is widely used to estimate sap flow and
      transpiration in conducting organs of woody plants. Previous studies have
      reported a natural azimuthal variability in sap flow, which could have practical
      implications in locating the CHP probes and integrating their output. Sap flow of
      several olive trees (Olea europaea L. cv. 'Arbequina') previously grown under
      different irrigation treatments were monitored by the CHP method, and their xylem
      anatomical characteristics were analyzed from wood samples taken at the same
      location in which the probes were installed. A significant azimuthal variability
      in the sap flow was found in a well-irrigated olive tree monitored by eight CHP
      probes. The azimuthal variability was well related to crown architecture, but
      poorly to azimuthal differences in the xylem anatomical characteristics. Well
      irrigated and deficit-irrigated olive trees showed similar xylem anatomical
      characteristics, but they differed in xylem growth and in the ratio of nocturnal
      to-diurnal sap flow (N/D index). The results of this work indicate that
      transpiration cannot be accurately estimated by the CHP method in olive trees if
      a small number of sensors are employed and that the N/D index could be used as a
      sensitive water status indicator.

PMID- 21081653
TI  - Streamside trees: responses of male, female and hybrid cottonwoods to flooding.
AB  - Cottonwoods, riparian poplars, are dioecious and prior studies have indicated
      that female poplars and willows can be more abundant than males in low-elevation
      zones, which are occasionally flooded. We investigated the response to flooding
      of clonal saplings of 12 male and 9 female narrowleaf cottonwoods (Populus
      angustifolia) grown for 15 weeks in a greenhouse, along with three females of a
      co-occurring native hybrid (Populus * jackii = Populus deltoides * Populus
      balsamifera). Three water-level treatments were provided, with substrate
      inundation as the flood treatment. In the non-flooded condition, the hybrids
      produced about four-fold more dry weight (DW) than the narrowleaf cottonwoods (P
      < 0.01). In both cottonwood taxa, flooding reduced stem height and DW, root and
      leaf area and weight, leaf chlorophyll and stomatal conductance (all P < 0.01).
      Inundation increased the foliar carbon-to-nitrogen ratio (+11%; P < 0.05) but did
      not significantly alter leaf water potential (mean -1.5 MPa), or foliar
      delta(13)C, which was lower in P. angustifolia (-32.80/00) than P. * jackii (
      31.50/00; P < 0.05). Water level influenced the root distribution as roots were
      sparse in the saturated substrate and abundant in the capillary fringe above. The
      male and female P. angustifolia genotypes grew similarly with the favorable water
      levels, but the males tended to be more inhibited by flooding. Sapling DW of
      males was reduced by 56% compared with a 44% reduction for females (P = 0.1), and
      there were similar lower reductions for leaf, stem and root DW in females. These
      results demonstrate the inundation response of floodplain trees and suggest
      relative flood tolerance as: P. angustifolia female > P. angustifolia male > P. *
      jackii female. This indicates that narrowleaf cottonwoods are relatively flood
      tolerant and suggests that females are more flood tolerant than males. We propose
      the concept of 'strategic positioning', whereby the seed-producing females could
      be better adapted to naturally flooded, low-elevation streamside zones where
      seedling recruitment generally occurs.

PMID- 21081654
TI  - Global patterns of genetic diversity and signals of natural selection for human
      ADME genes.
AB  - Genetic polymorphisms in many genes related to drug absorption, distribution,
      metabolism and excretion (ADME genes) contribute to the high heterogeneity of
      drug responses in humans. However, the extent to which genetic variation in ADME
      genes may contribute to differences among human populations in drug responses has
      not been studied. In this work, we investigate the global distribution of genetic
      diversity for 31 core and 252 extended ADME genes. We find that many important
      ADME genes are highly differentiated across continental regions. Additionally, we
      analyze the genetic differentiation associated with clinically relevant,
      functional polymorphism alleles, which is important for evaluating potential
      among-population heterogeneity in drug treatment effects. We find that ADME genes
      show significantly greater variation in levels of population differentiation, and
      we find numerous signals of recent positive selection on ADME genes. These
      results suggest that genetic differentiation at ADME genes could contribute to
      population heterogeneity in drug responses.

PMID- 21081655
TI  - The ability to form primary tumor xenografts is predictive of increased risk of
      disease recurrence in early-stage non-small cell lung cancer.
AB  - PURPOSE: Primary tumor xenografts (PTXG) established directly from patients'
      primary tumors in immunosuppressed animals might represent the spectrum of
      histologic complexity of lung cancers better than xenografts derived from
      established cell lines. These models are important in the study of aberrant
      biological pathways in cancers and as preclinical models for testing new
      therapeutic agents. However, not all primary tumors engraft when implanted into
      immunosuppressed mice. We have investigated factors that may influence the
      ability of primary non-small cell lung cancer (NSCLC) to form xenografts and
      their association with clinical outcome. EXPERIMENTAL DESIGN: Tumor fragments
      from patients undergoing curative surgery were implanted into NOD-SCID (nonobese
      diabetic-severely combined immunodeficient) mice within 24 hours of surgery.
      Patient characteristics for tumors that engrafted (XG) and did not engraft (no
      XG) were compared. Patient tumor DNA was profiled for the presence of 238 known
      mutations in 19 cancer-associated genes by using the MassARRAY platform. RESULTS:
      Xenografts were established and passaged successfully from 63 of 157 (40%)
      implanted NSCLCs. Tumor factors associated with engraftment included squamous
      histology, poor differentiation, and larger tumor size. Significantly fewer EGFR
      (epidermal growth factor receptor)-mutated tumors engrafted (P = 0.03);
      conversely, more K-RAS-mutated tumors engrafted (P = 0.05). In multivariate
      analysis including age, sex, stage, and mutation, patients with XG tumors had
      significantly shorter disease-free survival compared with no-XG patients (hazard
      ratio: 7.0, 95% CI: 3.1-15.81; P < 0.000003). CONCLUSION: PTXGs closely mirror
      the histology and molecular profiles of primary tumors and therefore may serve as
      important preclinical models. Tumors that engraft are biologically more
      aggressive and may be more representative of cancers with a higher propensity to
      relapse after surgery.

PMID- 21081656
TI  - Pazopanib reveals a role for tumor cell B-Raf in the prevention of HER2+ breast
      cancer brain metastasis.
AB  - PURPOSE: Brain metastases of breast cancer contribute significantly to patient
      morbidity and mortality. We have tested pazopanib, a recently approved
      antiangiogenic drug that targets VEGFR1, VEGFR2, VEGFR3, PDGFRbeta, PDGFRalpha,
      and c-kit, for prevention of experimental brain metastases and mechanism of
      action. EXPERIMENTAL DESIGN: In vitro assays included B-Raf enzymatic assays,
      Western blots, and angiogenesis assays. For in vivo assays, HER2 transfectants of
      the brain seeking sublines of MDA-MB-231 cells (231-BR-HER2) and MCF7 cells (MCF7
      HER2-BR3, derived herein) were injected into the left cardiac ventricle of mice
      and treated with vehicle or pazopanib beginning on day 3 postinjection. Brain
      metastases were counted histologically, imaged, and immunostained. RESULTS:
      Treatment with 100 mg/kg of pazopanib resulted in a 73% decline in large 231-BR
      HER2 metastases (P < 0.0001) and a 39% decline in micrometastases (P = 0.004). In
      vitro, pazopanib was directly antiproliferative to 231-BR-HER2 breast cancer
      cells and inhibited MEK and ERK activation in vitro despite B-Raf and Ras
      mutations. Enzymatic assays demonstrated that pazopanib directly inhibited the
      wild type and exon 11 oncogenic mutant, but not the V600E mutant forms of B-Raf.
      Activation of the B-Raf targets pERK1/2 and pMEK1/2 was decreased in pazopanib
      treated brain metastases whereas blood vessel density was unaltered. In the MCF7
      HER2-BR3 experimental brain metastasis model, pazopanib reduced overall brain
      metastasis volume upon magnetic resonance imaging (MRI) by 55% (P = 0.067),
      without affecting brain metastasis vascular density. CONCLUSIONS: The data
      identify a new activity for pazopanib directly on tumor cells as a pan-Raf
      inhibitor and suggest its potential for prevention of brain metastatic
      colonization of HER2(+) breast cancer.

PMID- 21081657
TI  - A pharmacodynamic study of docetaxel in combination with the P-glycoprotein
      antagonist tariquidar (XR9576) in patients with lung, ovarian, and cervical
      cancer.
AB  - PURPOSE: P-glycoprotein (Pgp) antagonists have been difficult to develop because
      of complex pharmacokinetic interactions and a failure to show meaningful results.
      Here we report the results of a pharmacokinetic and pharmacodynamic trial using a
      third-generation, potent, noncompetitive inhibitor of Pgp, tariquidar (XR9576),
      in combination with docetaxel. EXPERIMENTAL DESIGN: In the first treatment cycle,
      the pharmacokinetics of docetaxel (40 mg/m(2)) were evaluated after day 1 and day
      8 doses, which were administered with or without tariquidar (150 mg). (99m)Tc
      sestamibi scanning and CD56(+) mononuclear cell rhodamine efflux assays were
      conducted to assess Pgp inhibition. In subsequent cycles, 75 mg/m(2) docetaxel
      was administered with 150 mg tariquidar every 3 weeks. RESULTS: Forty-eight
      patients were enrolled onto the trial. Nonhematologic grade 3/4 toxicities in 235
      cycles were minimal. Tariquidar inhibited Pgp-mediated rhodamine efflux from
      CD56(+) cells and reduced (99m)Tc-sestamibi clearance from the liver. There was
      striking variability in basal sestamibi uptake; a 12% to 24% increase in visible
      lesions was noted in 8 of 10 patients with lung cancer. No significant difference
      in docetaxel disposition was observed in pairwise comparison with and without
      tariquidar. Four partial responses (PR) were seen (4/48); 3 in the non-small cell
      lung cancer (NSCLC) cohort, measuring 40%, 57%, and 67% by RECIST, and 1 PR in a
      patient with ovarian cancer. CONCLUSIONS: Tariquidar is well tolerated, with less
      observed systemic pharmacokinetic interaction than previous Pgp antagonists.
      Variable effects of tariquidar on retention of sestamibi in imageable lung
      cancers suggest that follow-up studies assessing tumor drug uptake in this
      patient population would be worthwhile.

PMID- 21081658
TI  - Atlas of gene expression in the mouse kidney: new features of glomerular parietal
      cells.
AB  - To gain molecular insight into kidney function, we performed a high-resolution
      quantitative analysis of gene expression in glomeruli and nine different nephron
      segments dissected from mouse kidney using Serial Analysis of Gene Expression
      (SAGE). We also developed dedicated bioinformatics tools and databases to
      annotate mRNA tags as transcripts. Over 800,000 mRNA SAGE tags were sequenced
      corresponding to >20,000 different mRNA tags present at least twice in at least
      one library. Hierarchical clustering analysis of tags demonstrated similarities
      between the three anatomical subsegments of the proximal tubule, between the
      cortical and medullary segments of the thick ascending limb of Henle's loop, and
      between the three segments constituting the aldosterone-sensitive distal nephron
      segments, whereas the glomerulus and distal convoluted tubule clusterized
      independently. We also identified highly specific mRNA markers of each subgroup
      of nephron segments and of most nephron segments. Tag annotation also identified
      numbers of putative antisense mRNAs. This database constitutes a reference
      resource in which the quantitative expression of a given gene can be compared
      with that of other genes in the same nephron segment, or between different
      segments of the nephron. To illustrate possible applications of this database, we
      performed a deeper analysis of the glomerulus transcriptome that unexpectedly
      revealed expression of several ion and water carriers; within the glomerulus,
      they were found to be preferentially expressed in the parietal sheet. It also
      revealed the major role of the zinc finger transcription factor Wt1 in the
      specificity of gene expression in the glomerulus. Finally, functional annotation
      of glomerulus-specific transcripts suggested a high proliferation activity of
      glomerular cells. Immunolabeling for PCNA confirmed a high percentage of
      proliferating cells in the glomerulus parietal sheet.

PMID- 21081659
TI  - Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control
      human mesenchymal stem cell phenotype via EPAS1.
AB  - Mesenchymal stem cells (MSCs) are present in a wide variety of tissues during
      development of the human embryo starting as early as the first trimester. Gene
      expression profiling of these cells has focused primarily on the molecular signs
      characterizing their potential heterogeneity and their differentiation potential.
      In contrast, molecular mechanisms participating in the emergence of MSC identity
      in embryo are still poorly understood. In this study, human embryonic stem cells
      (hESs) were differentiated toward MSCs (ES-MSCs) to compare the genetic patterns
      between pluripotent hESs and multipotent MSCs by a large genomewide expression
      profiling of mRNAs and microRNAs (miRNAs). After whole genome differential
      transcriptomic analysis, a stringent protocol was used to search for genes
      differentially expressed between hESs and ES-MSCs, followed by several validation
      steps to identify the genes most specifically linked to the MSC phenotype. A
      network was obtained that encompassed 74 genes in 13 interconnected
      transcriptional systems that are likely to contribute to MSC identity. Pairs of
      negatively correlated miRNAs and mRNAs, which suggest miRNA-target relationships,
      were then extracted and validation was sought with the use of Pre-miRs. We report
      here that underexpression of miR-148a and miR-20b in ES-MSCs, compared with ESs,
      allows an increase in expression of the EPAS1 (Endothelial PAS domain 1)
      transcription factor that results in the expression of markers of the MSC
      phenotype specification.

PMID- 21081660
TI  - A gene expression signature for insulin resistance.
AB  - Insulin resistance is a heterogeneous disorder caused by a range of genetic and
      environmental factors, and we hypothesize that its etiology varies considerably
      between individuals. This heterogeneity provides significant challenges to the
      development of effective therapeutic regimes for long-term management of type 2
      diabetes. We describe a novel strategy, using large-scale gene expression
      profiling, to develop a gene expression signature (GES) that reflects the overall
      state of insulin resistance in cells and patients. The GES was developed from 3T3
      L1 adipocytes that were made "insulin resistant" by treatment with tumor necrosis
      factor-alpha (TNF-alpha) and then reversed with aspirin and troglitazone
      ("resensitized"). The GES consisted of five genes whose expression levels best
      discriminated between the insulin-resistant and insulin-resensitized states. We
      then used this GES to screen a compound library for agents that affected the GES
      genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen
      when insulin resistance was successfully reversed with aspirin and troglitazone.
      This screen identified both known and new insulin-sensitizing compounds including
      nonsteroidal anti-inflammatory agents, beta-adrenergic antagonists, beta-lactams,
      and sodium channel blockers. We tested the biological relevance of this GES in
      participants in the San Antonio Family Heart Study (n = 1,240) and showed that
      patients with the lowest GES scores were more insulin resistant (according to
      HOMA_IR and fasting plasma insulin levels; P < 0.001). These findings show that
      GES technology can be used for both the discovery of insulin-sensitizing
      compounds and the characterization of patients into subtypes of insulin
      resistance according to GES scores, opening the possibility of developing a
      personalized medicine approach to type 2 diabetes.

PMID- 21081661
TI  - From alpaca to zebrafish: hammerhead ribozymes wherever you look.
AB  - The hammerhead ribozyme was originally discovered in subviral plant pathogens and
      was subsequently also found in a few other genomic locations. Using a secondary
      structure-based descriptor, we have searched publicly accessible sequence
      databases for new examples of type III hammerhead ribozymes. The more than 60,000
      entries fulfilling the descriptor were filtered with respect to folding and
      stability parameters that were experimentally validated. This resulted in a set
      of 284 unique motifs, of which 124 represent database entries of known hammerhead
      ribozymes from subviral plant pathogens and A. thaliana. The remainder are 160
      novel ribozyme candidates in 50 different eukaryotic genomes. With a few
      exceptions, the ribozymes were found either in repetitive DNA sequences or in
      introns of protein coding genes. Our data, which is complementary to a study by
      De la Pena and Garcia-Robles in 2010, indicate that the hammerhead is the most
      abundant small endonucleolytic ribozyme, which, in view of no sequence
      conservation beyond the essential nucleotides, likely has evolved independently
      in different organisms.

PMID- 21081662
TI  - The role of DNA helicases and their interaction partners in genome stability and
      meiotic recombination in plants.
AB  - DNA helicases are enzymes that are able to unwind DNA by the use of the energy
      equivalent ATP. They play essential roles in DNA replication, DNA repair, and DNA
      recombination in all organisms. As homologous recombination occurs in somatic and
      meiotic cells, the same proteins may participate in both processes, albeit not
      necessarily with identical functions. DNA helicases involved in genome stability
      and meiotic recombination are the focus of this review. The role of these enzymes
      and their characterized interaction partners in plants will be summarized.
      Although most factors are conserved in eukaryotes, plant-specific features are
      becoming apparent. In the RecQ helicase family, Arabidopsis thaliana RECQ4A has
      been shown before to be the functional homologue of the well-researched baker's
      yeast Sgs1 and human BLM proteins. It was surprising to find that its interaction
      partners AtRMI1 and AtTOP3alpha are absolutely essential for meiotic
      recombination in plants, where they are central factors of a formerly
      underappreciated dissolution step of recombination intermediates. In the
      expanding group of anti-recombinases, future analysis of plant helicases is
      especially promising. While no FBH1 homologue is present, the Arabidopsis genome
      contains homologues of both SRS2 and RTEL1. Yeast and mammals, on the other hand.
      only possess homologues of either one or the other of these helicases. Plants
      also contain several other classes of helicases that are known from other
      organisms to be involved in the preservation of genome stability: FANCM is
      conserved with parts of the human Fanconi anaemia proteins, as are homologues of
      the Swi2/Snf2 family and of PIF1.

PMID- 21081663
TI  - The lipoxygenase-dependent oxygenation of lipid body membranes is promoted by a
      patatin-type phospholipase in cucumber cotyledons.
AB  - Oilseed germination is characterized by the mobilization of storage lipids as a
      carbon and energy source for embryonic growth. In addition to storage lipid
      degradation in germinating oilseeds via the direct action of a triacylglycerol
      lipase (TGL) on the storage lipids, a second degradation pathway that is
      dependent on a specific lipid body trilinoleate 13-lipoxygenase (13-LOX) has been
      proposed in several plant species. The activity of this specific 13-LOX leads
      first to the formation of ester lipid hydroperoxides. These hydroperoxy fatty
      acids are then preferentially cleaved off by a TGL and serve as a substrate for
      glyoxysomal beta-oxidation. As a prerequisite for triacylglycerol (TAG)
      mobilization, a partial degradation of the phospholipid monolayer and/or membrane
      proteins of the oil body has been discussed. Evidence has now been found for both
      processes: partial degradation of the proteins caleosin and oleosin was observed
      and simultaneously a patatin-like protein together with transient phospholipase
      (PLase) activity could be detected at the oil body membranes during germination.
      Moreover, in vitro experiments with isolated oil bodies from mature seeds
      revealed that the formation of 13-LOX-derived lipid peroxides in lipid body
      membranes is increased after incubation with the purified recombinant patatin
      like protein. These experiments suggest that in vivo the degradation of storage
      lipids in cucumber cotyledons is promoted by the activity of a specific oil body
      PLase, which leads to an increased decomposition of the oil body membrane by the
      13-LOX and thereby TAGs may be better accessible to LOX and TGL.

PMID- 21081665
TI  - Functional diversity inside the Arabidopsis polyamine oxidase gene family.
AB  - Polyamine oxidases (PAOs) are FAD-dependent enzymes involved in polyamine
      catabolism. All so far characterized PAOs from monocotyledonous plants, such as
      the apoplastic maize PAO, oxidize spermine (Spm) and spermidine (Spd) to produce
      1,3-diaminopropane, H(2)O(2), and an aminoaldehyde, and are thus considered to be
      involved in a terminal catabolic pathway. Mammalian PAOs oxidize Spm or Spd
      (and/or their acetyl derivatives) differently from monocotyledonous PAOs,
      producing Spd or putrescine, respectively, in addition to H(2)O(2) and an
      aminoaldehyde, and are therefore involved in a polyamine back-conversion pathway.
      In Arabidopsis thaliana, five PAOs (AtPAO1-AtPAO5) are present with cytosolic or
      peroxisomal localization and three of them (the peroxisomal AtPAO2, AtPAO3, and
      AtPAO4) form a distinct PAO subfamily. Here, a comparative study of the catalytic
      properties of recombinant AtPAO1, AtPAO2, AtPAO3, and AtPAO4 is presented, which
      shows that all four enzymes strongly resemble their mammalian counterparts, being
      able to oxidize the common polyamines Spd and/or Spm through a polyamine back
      conversion pathway. The existence of this pathway in Arabidopsis plants is also
      evidenced in vivo. These enzymes are also able to oxidize the naturally occurring
      uncommon polyamines norspermine and thermospermine, the latter being involved in
      important plant developmental processes. Furthermore, data herein reveal some
      important differences in substrate specificity among the various AtPAOs, which
      suggest functional diversity inside the AtPAO gene family. These results
      represent a new starting point for further understanding of the physiological
      role(s) of the polyamine catabolic pathways in plants.

PMID- 21081664
TI  - Nuclear activity of sperm cells during Hyacinthus orientalis L. in vitro pollen
      tube growth.
AB  - In this study, the transcriptional state and distribution of RNA polymerase II,
      pre-mRNA splicing machinery elements, and rRNA transcripts were investigated in
      the sperm cells of Hyacinthus orientalis L. during in vitro pollen tube growth.
      During the second pollen mitosis, no nascent transcripts were observed in the
      area of the dividing generative cell, whereas the splicing factors were present
      and their pools were divided between newly formed sperm cells. Just after their
      origin, the sperm cells were shown to synthesize new RNA, although at a markedly
      lower level than the vegetative nucleus. The occurrence of RNA synthesis was
      accompanied by the presence of RNA polymerase II and a rich pool of splicing
      machinery elements. Differences in the spatial pattern of pre-mRNA splicing
      factors localization reflect different levels of RNA synthesis in the vegetative
      nucleus and sperm nuclei. In the vegetative nucleus, they were localized
      homogenously, whereas in the sperm nuclei a mainly speckled pattern of small
      nuclear RNA with a trimethylguanosine cap (TMG snRNA) and SC35 protein
      distribution was observed. As pollen tube growth proceeded, inhibition of RNA
      synthesis in the sperm nuclei was observed, which was accompanied by a gradual
      elimination of the splicing factors. In addition, analysis of rRNA localization
      indicated that the sperm nuclei are likely to synthesize some pool of rRNA at the
      later steps of pollen tube. It is proposed that the described changes in the
      nuclear activity of H. orientalis sperm cells reflect their maturation process
      during pollen tube growth, and that mature sperm cells do not carry into the
      zygote the nascent transcripts or the splicing machinery elements.

PMID- 21081666
TI  - Nuclear import of histone deacetylase 5 by requisite nuclear localization signal
      phosphorylation.
AB  - Histone deacetylase 5 (HDAC5), a class IIa deacetylase, is a prominent regulator
      of cellular and epigenetic processes that underlie the progression of human
      disease, ranging from cardiac hypertrophy to cancer. Although it is established
      that phosphorylation mediates 14-3-3 protein binding and provides the essential
      link between HDAC5 nucleo-cytoplasmic shuttling and transcriptional repression,
      thus far only four phospho-acceptor sites have been functionally characterized.
      Here, using a combinatorial proteomics approach and phosphomutant screening, we
      present the first evidence that HDAC5 has at least 17 in vivo phosphorylation
      sites within functional domains, including Ser278 and Ser279 within the nuclear
      localization signal (NLS), Ser1108 within the nuclear export signal, and Ser755
      in deacetylase domain. Global and targeted MS/MS analyses of NLS peptides
      demonstrated the presence of single (Ser278 and Ser279) and double
      (Ser278/Ser279) phosphorylations. The double S278/279A mutation showed reduced
      association with HDAC3, slightly decreased deacetylation activity, and
      significantly increased cytoplasmic localization compared with wild type HDAC5,
      whereas the S278A and S1108A phosphomutants were not altered. Live cell imaging
      revealed a deficiency in nuclear import of S278/279A HDAC5. Phosphomutant stable
      cell lines confirmed the cellular redistribution of NLS mutants and revealed a
      more pronounced cytoplasmic localization for the single S279A mutant. Proteomic
      analysis of immunoisolated S278/279A, S279A, and S259/498A mutants linked altered
      cellular localization to changes in protein interactions. S278/279A and S279A
      HDAC5 showed reduced association with the NCoR-HDAC3 nuclear corepressor complex
      as well as protein kinase D enzymes, which were potentiated in the S259/498A
      mutant. These results provide the first link between phosphorylation outside the
      known 14-3-3 sites and downstream changes in protein interactions. Together these
      studies identify Ser279 as a critical phosphorylation within the NLS involved in
      the nuclear import of HDAC5, providing a regulatory point in nucleo-cytoplasmic
      shuttling that may be conserved in other class IIa HDACs-HDAC4 and HDAC9.

PMID- 21081667
TI  - Peptides presented by HLA-DR molecules in synovia of patients with rheumatoid
      arthritis or antibiotic-refractory Lyme arthritis.
AB  - Disease-associated HLA-DR molecules, which may present autoantigens, constitute
      the greatest genetic risk factor for rheumatoid arthritis (RA) and antibiotic
      refractory Lyme arthritis (LA). The peptides presented by HLA-DR molecules in
      synovia have not previously been defined. Using tandem mass spectrometry,
      rigorous database searches, and manual spectral interpretation, we identified
      1,427 HLA-DR-presented peptides (220-464 per patient) from the synovia of four
      patients, two diagnosed with RA and two diagnosed with LA. The peptides were
      derived from 166 source proteins, including a wide range of intracellular and
      plasma proteins. A few epitopes were found only in RA or LA patients. However,
      two patients with different diseases who had the same HLA allele had the largest
      number of epitopes in common. In one RA patient, peptides were identified as
      originating from source proteins that have been reported to undergo
      citrullination under other circumstances, yet neither this post-translational
      modification nor anti-cyclic citrullinated peptide antibodies were detected.
      Instead, peptides with the post-translational modification of S-cysteinylation
      were identified. We conclude that a wide range of proteins enter the HLA-DR
      pathway of antigen-presenting cells in the patients' synovial tissue, and their
      HLA-DR genotype, not the disease type, appears to be the primary determinant of
      their HLA-DR-peptide repertoire. New insights into the naturally presented HLA-DR
      epitope repertoire in target tissues may allow the identification of pathogenic T
      cell epitopes, and this could lead to innovative therapeutic interventions.

PMID- 21081668
TI  - Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation:
      conformational selection highlights a new concept in allosteric inhibitor design.
AB  - The regulatory (R) subunit of protein kinase A serves to modulate the activity of
      protein kinase A in a cAMP-dependent manner and exists in two distinct and
      structurally dissimilar, end point cAMP-bound "B" and C-subunit-bound "H"
      conformations. Here we report mechanistic details of cAMP action as yet unknown
      through a unique approach combining x-ray crystallography with structural
      proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass
      spectrometry, applied to the study of a stereospecific cAMP phosphorothioate
      analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R
      subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit
      crystallized in the H conformation, which was previously assumed to be induced
      only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but
      amide exchange mass spectrometry showed large differences between apo, agonist
      and antagonist-bound states of the R-subunit. Further ion mobility reveals the
      apo R-subunit as an ensemble of multiple conformations with collisional cross
      sectional areas spanning both the agonist and antagonist-bound states. Thus
      contrary to earlier studies that explained the basis for cAMP action through
      "induced fit" alone, we report evidence for conformational selection, where the
      ligand-free apo form of the R-subunit exists as an ensemble of both B and H
      conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS
      interestingly binds the H conformation. This reveals the unique importance of the
      equatorial oxygen of the cyclic phosphate in mediating conformational transitions
      from H to B forms highlighting a novel approach for rational structure-based drug
      design. Ideal inhibitors such as Rp-cAMPS are those that preferentially "select"
      inactive conformations of target proteins by satisfying all "binding" constraints
      alone without inducing conformational changes necessary for activation.

PMID- 21081669
TI  - Pediatric and adult gliomas: how different are they?

PMID- 21081671
TI  - Risk of radiation-induced breast cancer from mammographic screening.
AB  - PURPOSE: To assess a schema for estimating the risk of radiation-induced breast
      cancer following exposure of the breast to ionizing radiation as would occur with
      mammography and to provide data that can be used to estimate the potential number
      of breast cancers, cancer deaths, and woman-years of life lost attributable to
      radiation exposure delivered according to a variety of screening scenarios.
      MATERIALS AND METHODS: An excess absolute risk model was used to predict the
      number of radiation-induced breast cancers attributable to the radiation dose
      received for a single typical digital mammography examination. The algorithm was
      then extended to consider the consequences of various scenarios for routine
      screening beginning and ending at different ages, with examinations taking place
      at 1- or 2-year intervals. A life-table correction was applied to consider
      reductions of the cohort size over time owing to nonradiation-related causes of
      death. Finally, the numbers of breast cancer deaths and woman-years of life lost
      that might be attributable to the radiation exposure were calculated. Cancer
      incidence and cancer deaths were estimated for individual attained ages following
      the onset of screening, and lifetime risks were also calculated. RESULTS: For a
      cohort of 100 000 women each receiving a dose of 3.7 mGy to both breasts and who
      were screened annually from age 40 to 55 years and biennially thereafter to age
      74 years, it is predicted that there will be 86 cancers induced and 11 deaths due
      to radiation-induced breast cancer. CONCLUSION: For the mammographic screening
      regimens considered that begin at age 40 years, this risk is small compared with
      the expected mortality reduction achievable through screening. The risk of
      radiation-induced breast cancer should not be a deterrent from mammographic
      screening of women over the age of 40 years.

PMID- 21081672
TI  - Global processing speed in children with low reading ability and in children and
      adults with typical reading ability: exploratory factor analytic models.
AB  - PURPOSE: To investigate processing speed as a latent dimension in children with
      dyslexia and children and adults with typical reading skills. METHOD: Exploratory
      factor analysis (FA) was based on a sample of multigenerational families, each
      ascertained through a child with dyslexia. Eleven measures--6 of them timed-
      represented verbal and nonverbal processes, alphabet writing, and motor
      sequencing in the hand and oral motor system. FA was conducted in 4 cohorts (all
      children, a subset of children with low reading scores, a subset of children with
      typical reading scores, and adults with typical reading scores; total N = 829).
      RESULTS: Processing speed formed the first factor in all cohorts. Both measures
      of motor sequencing speed loaded on the speed factor with the other timed
      variables. Children with poor reading scores showed lower speed factor scores
      than did typical peers. The speed factor was negatively correlated with age in
      the adults. CONCLUSIONS: The speed dimension was observed independently of
      participant cohort, gender, and reading ability. Results are consistent with a
      unified theory of processing speed as a quadratic function of age in typical
      development and with slowed processing in poor readers.

PMID- 21081673
TI  - Comparing two methods for reducing variability in voice quality measurements.
AB  - PURPOSE: Interrater disagreements in ratings of quality plague the study of
      voice. This study compared 2 methods for handling this variability. METHOD:
      Listeners provided multiple breathiness ratings for 2 sets of pathological
      voices, one including 20 male and 20 female voices unselected for quality and one
      including 20 breathy female voices. Ratings for each listener were averaged
      together, mean ratings were z transformed, and the likelihood that 2 listeners
      would agree exactly in their ratings was calculated as a function of averaging
      and standardizing condition. Data were also multidimensionally scaled to examine
      similarities among listeners in perceptual strategy. Results were compared with
      parallel analyses of existing breathiness ratings of the same voices gathered
      using a method-of-adjustment task. RESULTS: Three-way interactions between the
      mean rating for a voice, standardization condition, and the number of voices
      averaged together were observed, but no main effect of averaging condition
      emerged. Multidimensional scaling revealed significant residual differences in
      perceptual strategy across listeners after averaging and standardizing. Ratings
      from the method-of-adjustment task showed both high agreement levels and
      consistent perceptual strategies across listeners, as theoretically predicted.
      CONCLUSION: Averaging multiple ratings and standardizing the mean are inadequate
      in addressing variations in voice quality perception.

PMID- 21081674
TI  - Sensitivity and specificity of French language and processing measures for the
      identification of primary language impairment at age 5.
AB  - PURPOSE: Research on the diagnostic accuracy of different language measures has
      focused primarily on English. This study examined the sensitivity and specificity
      of a range of measures of language knowledge and language processing for the
      identification of primary language impairment (PLI) in French-speaking children.
      Because of the lack of well-documented language measures in French, it is
      difficult to accurately identify affected children, and thus research in this
      area is impeded. METHOD: The performance of 14 monolingual French-speaking
      children with confirmed, clinically identified PLI (M = 61.4 months of age, SD =
      7.2 months) on a range of language and language processing measures was compared
      with the performance of 78 children with confirmed typical language development
      (M age = 58.9 months, SD = 5.7). These included evaluations of receptive
      vocabulary, receptive grammar, spontaneous language, narrative production,
      nonword repetition, sentence imitation, following directions, rapid automatized
      naming, and digit span. Sensitivity, specificity, and likelihood ratios were
      determined at 3 cutoff points: (a) -1 SD, (b) -1.28 SD, and (b) -2 SD below mean
      values. Receiver operator characteristic curves were used to identify the most
      accurate cutoff for each measure. RESULTS: Significant differences between the
      PLI and typical language development groups were found for the majority of the
      language measures, with moderate to large effect sizes. The measures differed in
      their sensitivity and specificity, as well as in which cutoff point provided the
      most accurate decision. Ideal cutoff points were in most cases between the mean
      and -1 SD. Sentence imitation and following directions appeared to be the most
      accurate measures. CONCLUSIONS: This study provides evidence that standardized
      measures of language and language processing provide accurate identification of
      PLI in French. The results are strikingly similar to previous results for
      English, suggesting that in spite of structural differences between the
      languages, PLI in both languages involves a generalized language delay across
      linguistic domains, which can be identified in a similar way using existing
      standardized measures.

PMID- 21081675
TI  - Research ethics III: Publication practices and authorship, conflicts of interest,
      and research misconduct.
AB  - PURPOSE: In this series of articles--Research Ethics I, Research Ethics II, and
      Research Ethics III--the authors provide a comprehensive review of the 9 core
      domains for the responsible conduct of research (RCR) as articulated by the
      Office of Research Integrity. METHOD: In Research Ethics III, they review the RCR
      domains of publication practices and authorship, conflicts of interest, and
      research misconduct. Whereas the legal definition of research misconduct under
      federal law pertains mainly to intentional falsification, fabrication, and
      plagiarism, they discuss a host of research practices that raise ethical
      concerns. CONCLUSIONS: The integrity of the scientific record--its accuracy,
      completeness, and value--ultimately impacts the health and well-being of society.
      For this reason, scientists are both entrusted and obligated to use the highest
      standards possible when proposing, performing, reviewing, and reporting research
      or when educating and mentoring new investigators.

PMID- 21081676
TI  - Ethical principles associated with the publication of research in ASHA's
      scholarly journals: importance and adequacy of coverage.
AB  - PURPOSE: The purpose of this 2-part study was to determine the importance of
      specific topics relating to publication ethics and adequacy of the American
      Speech-Language-Hearing Association's (ASHA's) policies regarding these topics.
      METHOD: A 56-item Web-based survey was sent to (a) ASHA journal editors,
      associate editors, and members of the Publications Board (Group 1); (b) authors,
      reviewers, and members of ASHA's Board of Ethics (Group 2); and (c) a random
      sample of the ASHA membership, characterized as journal readers (Group 3). The
      survey contained 4 questions related to ethical principles associated with the
      publication of research: (a) In regard to scientific integrity in research
      publications in general, how important is the issue of [topic]? (b) Should ASHA
      publication policies address this issue? (c) Do ASHA policies address this issue?
      (d) If yes, how adequately do ASHA policies address this issue? A second study
      evaluated the contents of ASHA's publication policy documents in regard to their
      coverage of the survey topics. RESULTS: Results indicated many of the topics
      deemed most important by all groups were included in ASHA's publication policy
      documents; other topics, although included, were not adequately addressed.
      CONCLUSIONS: ASHA needs a single, unifying publication policy document, and
      increased education of all groups in the realm of ethics in the publication
      process is indicated.

PMID- 21081678
TI  - Research Integrity in Communication Sciences and Disorders.
AB  - PURPOSE: A joint program on "research on research integrity" sponsored by the
      National Institute of Neurological Disorders and Stroke (NINDS) and the Office of
      Research Integrity (ORI) encouraged the examination of practices and policies
      promoting the responsible conduct of research (RCR). Our grant, Research
      Integrity in ASHA: Education and Publication (#NS44534), enabled ASHA's Research
      Integrity Grant Group (a) to identify patterns of teaching and learning in
      communication sciences and disorders graduate programs about specific topics of
      research integrity on the conduct of science, (b) to examine perceptions about
      concepts of research integrity as they apply to scientific journals within the
      discipline, and (c) to evaluate policies and practices established by ASHA to
      protect the integrity of published scientific work. METHOD: Historical and
      contemporary literature were reviewed, surveys were conducted, and ASHA policies
      were analyzed. CONCLUSION: This JSLHR supplement has been written with the aim of
      informing and inspiring scientists, students, research institutions, and
      professional societies to practice responsible research in the 21st century and
      beyond.

PMID- 21081677
TI  - Research ethics I: Responsible conduct of research (RCR)--historical and
      contemporary issues pertaining to human and animal experimentation.
AB  - PURPOSE: In this series of articles--Research Ethics I, Research Ethics II, and
      Research Ethics III--the authors provide a comprehensive review of the 9 core
      domains for the responsible conduct of research (RCR) as articulated by the
      Office of Research Integrity. In Research Ethics I, they present a historical
      overview of the evolution of RCR in the United States then examine the evolution
      of human and animal experimentation from the birth of scientific medicine through
      World War II to the present day. METHOD: They relied on authoritative documents,
      both historical and contemporary, insightful commentary, and empirical research
      in order to identify current issues and controversies of potential interest to
      both faculty and students. CONCLUSIONS: The authors have written this article
      from a historical perspective because they think all readers interested in RCR
      should appreciate how the history of science and all the good--and harm--it has
      produced can inform how researchers practice responsible research in the 21st
      century and beyond.

PMID- 21081679
TI  - Research ethics II: Mentoring, collaboration, peer review, and data management
      and ownership.
AB  - PURPOSE: In this series of articles--Research Ethics I, Research Ethics II, and
      Research Ethics III--the authors provide a comprehensive review of the 9 core
      domains for the responsible conduct of research (RCR) as articulated by the
      Office of Research Integrity. In Research Ethics II, the authors review the RCR
      domains of mentoring, collaboration, peer review, and data management and
      ownership. METHOD: They relied on authoritative documents, both historical and
      contemporary, insightful commentary, and empirical research in order to identify
      current issues and controversies of potential interest to both faculty and
      students. CONCLUSIONS: The authors close by urging readers to stay abreast of the
      manifold ethics issues facing today's community of scientists, policymakers, and
      research institutions, and to adhere to best practices as they evolve.

PMID- 21081680
TI  - Responsible conduct of research in communication sciences and disorders: faculty
      and student perceptions.
AB  - PURPOSE: Two Web-based surveys (Surveys I and II) were used to assess perceptions
      of faculty and students in Communication Sciences and Disorders (CSD) regarding
      the responsible conduct of research (RCR). METHOD: Survey questions addressed 9
      RCR domains thought important to the responsible conduct of research: (a) human
      subjects protections; (b) research involving animals; (c) publication practices
      and responsible authorship; (d) mentor/trainee responsibilities; (e)
      collaborative science; (f) peer review; (g) data acquisition, management,
      sharing, and ownership; (h) conflicts of interest; and (i) research misconduct.
      Respondents rated each of 37 topics for importance and for sufficiency of
      instructional coverage. RESULTS: Respondents to Survey I were 137 faculty members
      from 68 (26%) of the 261 graduate programs in CSD. By comparison, 237 students
      from 39 (15%) programs responded to Survey II. Data about the importance and
      sufficiency of coverage of each of the 37 items were transformed into z scores to
      reveal relative ratings among the 37 topics. Data presentations were grouped for
      topics in each of the 9 RCR domains. Ratings indicated the relatively high
      importance assigned among the 37 topics by CSD faculty and students. Sufficiency
      of coverage of those same topics received lower ratings. CONCLUSIONS: The results
      of these surveys support the notion that students in CSD perceive that they are
      receiving information about RCR. The data pertaining to sufficiency of coverage
      provide a basis for improving instruction in this important aspect of research
      education.

PMID- 21081682
TI  - Climate effect of inhaled anaesthetics.

PMID- 21081683
TI  - Cormack-Lehane classification revisited.

PMID- 21081684
TI  - Simultaneous epidural blood patches at different intervertebral spaces for
      spontaneous intracranial hypotension.

PMID- 21081685
TI  - Intravenous magnesium sulphate prevents intravenous salbutamol tachycardia in
      asthma.

PMID- 21081686
TI  - Dying brain.

PMID- 21081687
TI  - Headache and nuchal rigidity and photophobia after an epidural blood patch:
      diagnosis by exclusion of persistent post-dural puncture headache mimicking
      meningitis.

PMID- 21081688
TI  - Influence of ambient light on cerebral oximeters.

PMID- 21081689
TI  - 'Win with the chin', 'sniffing the morning air', or 'last orders at the bar'?

PMID- 21081691
TI  - A meta-analysis of the clinical remission rate and long-term efficacy of
      tonsillectomy in patients with IgA nephropathy.
AB  - BACKGROUND: We wished to evaluate the clinical remission rate and long-term
      efficacy of tonsillectomy for patients with IgA nephropathy. METHODS: We searched
      a number of databases, including PubMed, CNKI, Wanfang and others, for clinical
      case-control studies of tonsillectomy in patients with IgA nephropathy. We then
      performed a meta-analysis of these studies. After evaluating total clinical
      remission rates, we compared the remission rates for specific treatments:
      tonsillectomy plus steroid pulse, tonsillectomy plus normal-dose steroid, and
      general treatment using neither tonsillectomy nor steroids. We also compared the
      rates of end-stage renal failure (ESRF) at last follow-up to estimate the long
      term renal survival rate associated with each treatment. RESULTS: Seven
      retrospective studies met the inclusion criteria and were included. These
      included a total of 858 patients, in which 534 underwent tonsillectomy and 324
      did not. The total clinical remission rate was higher in the operative group,
      while the ESRF rate was higher in the non-operative group. The clinical remission
      rate in patients who underwent tonsillectomy remained higher than in the non
      operative group at both 5- and 10-year follow-up. The clinical remission rate in
      patients who underwent tonsillectomy plus steroid pulse was higher than in those
      treated with steroid pulse alone, normal-dose steroids or general treatment alone
      (P < 0.05). However, the clinical remission rate of simple tonsillectomy was not
      higher than that of general treatment (P > 0.05). CONCLUSIONS: Whereas neither
      tonsillectomy nor steroid treatment alone increased remission rates in patients
      with IgA nephropathy, tonsillectomy combined with either normal steroid or
      steroid pulse treatment resulted in higher remission rates with favourable long
      term efficacy.

PMID- 21081692
TI  - Transcription of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase
      is regulated by SF-1 in human adrenocortical cells: involvement of protein kinase
      A signal transduction pathway.
AB  - The study was designed to elucidate the influence of the protein kinase A (PKA)
      signal transduction pathway on transcription of the LIPE gene encoding hormone
      sensitive lipase/cholesteryl esterase (HSL) in H295R cells. HSL is one of the key
      enzymes involved in steroid hormone synthesis, and ACTH, with mediation of the
      PKA pathway, increases its activity. However, the mode of regulation of LIPE gene
      expression by ACTH remains unknown. It was found that stimulation of the PKA
      pathway by the adenylyl cyclase activator, forskolin, caused a twofold increase
      in LIPE transcript accompanied by appreciable rise in the protein product of the
      gene and cortisol output. RNA polymerase II inhibitor abolished, and protein
      synthesis inhibitor attenuated this effect. Forskolin and PKA catalytic subunit
      increased transcriptional activity of LIPE promoter A in cells transfected with
      the luciferase reporter vector. Overexpression of steroidogenic factor-1 (SF-1)
      increased LIPE promoter activity, while transient silencing of SF-1 expression
      with specific siRNAs abolished forskolin-stimulated LIPE transcription. It is
      concluded that ACTH via the PKA pathway stimulates expression of SF-1, which
      activates transcription of LIPE presumably by interaction with putative binding
      sequences within promoter A. A novel mechanism contributing to the long-term
      effect of ACTH on adrenal steroidogenesis is proposed: ACTH stimulates
      transcription of SF-1, which interacts with the putative SF-1-binding sequences
      within the promoter and activates LIPE transcription. An increased level of HSL
      results in an enhanced supply of cholesterol required for steroid hormone
      synthesis.

PMID- 21081693
TI  - Functional assignments for the carboxyl-terminal domains of the ferrochelatase
      from Synechocystis PCC 6803: the CAB domain plays a regulatory role, and region
      II is essential for catalysis.
AB  - Ferrochelatase (FeCH) catalyzes the insertion of Fe(2+) into protoporphyrin,
      forming protoheme. In photosynthetic organisms, FeCH and magnesium chelatase lie
      at a biosynthetic branch point where partitioning down the heme and chlorophyll
      (Chl) pathways occurs. Unlike their mammalian, yeast, and other bacterial
      counterparts, cyanobacterial and algal FeCHs as well as FeCH2 isoform from plants
      possess a carboxyl-terminal Chl a/b-binding (CAB) domain with a conserved Chl
      binding motif. The CAB domain is connected to the FeCH catalytic core by a
      proline-rich linker sequence (region II). In order to dissect the regulatory,
      catalytic, and structural roles of the region II and CAB domains, we analyzed a
      FeCH DeltaH347 mutant that retains region II but lacks the CAB domain and
      compared it with the DeltaH324-FeCH mutant that lacks both these domains. We
      found that the CAB domain is not required for catalytic activity but is essential
      for dimerization of FeCH; its absence causes aberrant accumulation of Chl-protein
      complexes under high light accompanied by high levels of the Chl precursor
      chlorophyllide. Thus, the CAB domain appears to serve mainly a regulatory
      function, possibly in balancing Chl biosynthesis with the synthesis of cognate
      apoproteins. Region II is essential for the catalytic function of the plastid
      type FeCH enzyme, although the low residual activity of the DeltaH324-FeCH is
      more than sufficient to furnish the cellular demand for heme. We propose that the
      apparent surplus of FeCH activity in the wild type is critical for cell viability
      under high light due to a regulatory role of FeCH in the distribution of Chl into
      apoproteins.

PMID- 21081694
TI  - Unraveling the evolution of auxin signaling.
AB  - Auxin signaling is central to plant growth and development, yet hardly anything
      is known about its evolutionary origin. While the presence of key players in
      auxin signaling has been analyzed in various land plant species, similar analyses
      in the green algal lineages are lacking. Here, we survey the key players in auxin
      biology in the available genomes of Chlorophyta species. We found that the
      genetic potential for auxin biosynthesis and AUXIN1 (AUX1)/LIKE AUX1- and P
      GLYCOPROTEIN/ATP-BINDING CASSETTE subfamily B-dependent transport is already
      present in several single-celled and colony-forming Chlorophyta species. In
      addition, our analysis of expressed sequence tag libraries from Coleochaete
      orbicularis and Spirogyra pratensis, green algae of the Streptophyta clade that
      are evolutionarily closer to the land plants than those of the Chlorophyta clade,
      revealed the presence of partial AUXIN RESPONSE FACTORs and/or AUXIN/INDOLE-3
      ACETIC ACID proteins (the key factors in auxin signaling) and PIN-FORMED-like
      proteins (the best-characterized auxin-efflux carriers). While the identification
      of these possible AUXIN RESPONSE FACTOR- and AUXIN/INDOLE-3-ACETIC ACID
      precursors and putative PIN-FORMED orthologs calls for a deeper investigation of
      their evolution after sequencing more intermediate genomes, it emphasizes that
      the canonical auxin response machinery and auxin transport mechanisms were, at
      least in part, already present before plants "moved" to land habitats.

PMID- 21081695
TI  - Structural and metabolic transitions of C4 leaf development and differentiation
      defined by microscopy and quantitative proteomics in maize.
AB  - C(4) grasses, such as maize (Zea mays), have high photosynthetic efficiency
      through combined biochemical and structural adaptations. C(4) photosynthesis is
      established along the developmental axis of the leaf blade, leading from an
      undifferentiated leaf base just above the ligule into highly specialized
      mesophyll cells (MCs) and bundle sheath cells (BSCs) at the tip. To resolve the
      kinetics of maize leaf development and C(4) differentiation and to obtain a
      systems-level understanding of maize leaf formation, the accumulation profiles of
      proteomes of the leaf and the isolated BSCs with their vascular bundle along the
      developmental gradient were determined using large-scale mass spectrometry. This
      was complemented by extensive qualitative and quantitative microscopy analysis of
      structural features (e.g., Kranz anatomy, plasmodesmata, cell wall, and
      organelles). More than 4300 proteins were identified and functionally annotated.
      Developmental protein accumulation profiles and hierarchical cluster analysis
      then determined the kinetics of organelle biogenesis, formation of cellular
      structures, metabolism, and coexpression patterns. Two main expression clusters
      were observed, each divided in subclusters, suggesting that a limited number of
      developmental regulatory networks organize concerted protein accumulation along
      the leaf gradient. The coexpression with BSC and MC markers provided strong
      candidates for further analysis of C(4) specialization, in particular
      transporters and biogenesis factors. Based on the integrated information, we
      describe five developmental transitions that provide a conceptual and practical
      template for further analysis. An online protein expression viewer is provided
      through the Plant Proteome Database.

PMID- 21081697
TI  - Tracing entire operation cycles of molecular motor hepatitis C virus helicase in
      structurally resolved dynamical simulations.
AB  - Hepatitis C virus helicase is a molecular motor that splits duplex DNA while
      actively moving over it. An approximate coarse-grained dynamical description of
      this protein, including its interactions with DNA and ATP, is constructed. Using
      such a mechanical model, entire operation cycles of an important protein machine
      could be followed in structurally resolved dynamical simulations. Ratcheting
      inchworm translocation and spring-loaded DNA unwinding, suggested by experimental
      data, were reproduced. Thus, feasibility of coarse-grained simulations, bridging
      a gap between full molecular dynamics and reduced phenomenological theories of
      molecular motors, has been demonstrated.

PMID- 21081696
TI  - Arabidopsis beta-ketoacyl-[acyl carrier protein] synthase i is crucial for fatty
      acid synthesis and plays a role in chloroplast division and embryo development.
AB  - Lipid metabolism plays a pivotal role in cell structure and in multiple plant
      developmental processes. beta-Ketoacyl-[acyl carrier protein] synthase I (KASI)
      catalyzes the elongation of de novo fatty acid (FA) synthesis. Here, we report
      the functional characterization of KASI in the regulation of chloroplast division
      and embryo development. Phenotypic observation of an Arabidopsis thaliana T-DNA
      insertion mutant, kasI, revealed multiple morphological defects, including
      chlorotic (in netted patches) and curly leaves, reduced fertility, and
      semidwarfism. There are only one to five enlarged chloroplasts in the mesophyll
      cells of chlorotic sectors of young kasI rosette leaves, indicating suppressed
      chloroplast division under KASI deficiency. KASI deficiency results in a
      significant change in the polar lipid composition, which causes the suppressed
      expression of FtsZ and Min system genes, disordered Z-ring placement in the
      oversized chloroplast, and inhibited polymerization of FtsZ protein at mid-site
      of the chloroplast in kasI. In addition, KASI deficiency results in disrupted
      embryo development before the globular stage and dramatically reduces FA levels
      (~33.6% of the wild type) in seeds. These results demonstrate that de novo FA
      synthesis is crucial and has pleiotropic effects on plant growth. The polar lipid
      supply is important for chloroplast division and development, revealing a key
      function of FA synthesis in plastid development.

PMID- 21081698
TI  - Structural basis for substrate activation and regulation by cystathionine beta
      synthase (CBS) domains in cystathionine {beta}-synthase.
AB  - The catalytic potential for H(2)S biogenesis and homocysteine clearance converge
      at the active site of cystathionine beta-synthase (CBS), a pyridoxal phosphate
      dependent enzyme. CBS catalyzes beta-replacement reactions of either serine or
      cysteine by homocysteine to give cystathionine and water or H(2)S, respectively.
      In this study, high-resolution structures of the full-length enzyme from
      Drosophila in which a carbanion (1.70 A) and an aminoacrylate intermediate (1.55
      A) have been captured are reported. Electrostatic stabilization of the
      zwitterionic carbanion intermediate is afforded by the close positioning of an
      active site lysine residue that is initially used for Schiff base formation in
      the internal aldimine and later as a general base. Additional stabilizing
      interactions between active site residues and the catalytic intermediates are
      observed. Furthermore, the structure of the regulatory "energy-sensing" CBS
      domains, named after this protein, suggests a mechanism for allosteric activation
      by S-adenosylmethionine.

PMID- 21081699
TI  - Dynamics of podosome stiffness revealed by atomic force microscopy.
AB  - Podosomes are unique cellular entities specifically found in macrophages and
      involved in cell-matrix interactions, matrix degradation, and 3D migration. They
      correspond to a core of F-actin surrounded at its base by matrix receptors. To
      investigate the structure/function relationships of podosomes, soft lithography,
      atomic force microscopy (AFM), and correlative fluorescence microscopy were used
      to characterize podosome physical properties in macrophages differentiated from
      human blood monocytes. Podosome formation was restricted to delineated areas with
      micropatterned fibrinogen to facilitate AFM analyses. Podosome height and
      stiffness were measured with great accuracy in living macrophages (578 +/- 209 nm
      and 43.8 +/- 9.3 kPa) and these physical properties were independent of the
      nature of the underlying matrix. In addition, time-lapse AFM revealed that
      podosomes harbor two types of overlapping periodic stiffness variations
      throughout their lifespan, which depend on F-actin and myosin II activity. This
      report shows that podosome biophysical properties are amenable to AFM, allowing
      the study of podosomes in living macrophages at nanoscale resolution and the
      analysis of their intimate dynamics. Such an approach opens up perspectives to
      better understand the mechanical functionality of podosomes under physiological
      and pathological contexts.

PMID- 21081701
TI  - Toward a whole-landscape approach for sustainable land use in the tropics.
AB  - Increasing food production and mitigating climate change are two primary but
      seemingly contradictory objectives for tropical landscapes. This special feature
      examines synergies and trade-offs among these objectives. Four themes emerge from
      the papers: the important roles of both forest and agriculture sectors for
      climate mitigation in tropical countries; the minor contribution from
      deforestation-related agricultural expansion to overall food production at global
      and continental scales; the opportunities for synergies between improved food
      production and reductions in greenhouse gas emissions through diversion of
      agricultural expansion to already-cleared lands, improved soil, crop, and
      livestock management, and agroforestry; and the need for targeted policy and
      management interventions to make these synergistic opportunities a reality. We
      conclude that agricultural intensification is a key factor to meet dual
      objectives of food production and climate mitigation, but there is no single
      panacea for balancing these objectives in all tropical landscapes. Place-specific
      strategies for sustainable land use emerge from assessments of current land use,
      demographics, and other biophysical and socioeconomic characteristics, using a
      whole-landscape, multisector perspective.

PMID- 21081700
TI  - Granulocyte-colony stimulating factor promotes lung metastasis through
      mobilization of Ly6G+Ly6C+ granulocytes.
AB  - Priming of the organ-specific premetastatic sites is thought to be an important
      yet incompletely understood step during metastasis. In this study, we show that
      the metastatic tumors we examined overexpress granulocyte-colony stimulating
      factor (G-CSF), which expands and mobilizes Ly6G+Ly6C+ granulocytes and
      facilitates their subsequent homing at distant organs even before the arrival of
      tumor cells. Moreover, G-CSF-mobilized Ly6G+Ly6C+ cells produce the Bv8 protein,
      which has been implicated in angiogenesis and mobilization of myeloid cells. Anti
      G-CSF or anti-Bv8 antibodies significantly reduced lung metastasis.
      Transplantation of Bv8 null fetal liver cells into lethally irradiated hosts also
      reduced metastasis. We identified an unexpected role for Bv8: the ability to
      stimulate tumor cell migration through activation of one of the Bv8 receptors,
      prokineticin receptor (PKR)-1. Finally, we show that administration of
      recombinant G-CSF is sufficient to increase the numbers of Ly6G+Ly6C+ cells in
      organ-specific metastatic sites and results in enhanced metastatic ability of
      several tumors.

PMID- 21081702
TI  - Opportunities for reducing greenhouse gas emissions in tropical peatlands.
AB  - The upcoming global mechanism for reducing emissions from deforestation and
      forest degradation in developing countries should include and prioritize tropical
      peatlands. Forested tropical peatlands in Southeast Asia are rapidly being
      converted into production systems by introducing perennial crops for lucrative
      agribusiness, such as oil-palm and pulpwood plantations, causing large greenhouse
      gas (GHG) emissions. The Intergovernmental Panel on Climate Change Guidelines for
      GHG Inventory on Agriculture, Forestry, and Other Land Uses provide an adequate
      framework for emissions inventories in these ecosystems; however, specific
      emission factors are needed for more accurate and cost-effective monitoring. The
      emissions are governed by complex biophysical processes, such as peat
      decomposition and compaction, nutrient availability, soil water content, and
      water table level, all of which are affected by management practices. We estimate
      that total carbon loss from converting peat swamp forests into oil palm is 59.4
      +/- 10.2 Mg of CO(2) per hectare per year during the first 25 y after land-use
      cover change, of which 61.6% arise from the peat. Of the total amount (1,486 +/-
      183 Mg of CO(2) per hectare over 25 y), 25% are released immediately from land
      clearing fire. In order to maintain high palm-oil production, nitrogen inputs
      through fertilizer are needed and the magnitude of the resulting increased N(2)O
      emissions compared to CO(2) losses remains unclear.

PMID- 21081703
TI  - Paullinia cupana Mart. var. Sorbilis protects human dopaminergic neuroblastoma SH
      SY5Y cell line against rotenone-induced cytotoxicity.
AB  - Paullinia cupana Mart. var. Sorbilis, commonly known as Guarana, is a Brazilian
      plant frequently cited for its antioxidant properties and different
      pharmacological activities on the central nervous system. The potential
      beneficial uses of Guarana in neurodegenerative disorders, such as in Parkinson's
      disease (PD), the pathogenesis of which is associated with mitochondrial
      dysfunction and oxidative stress, has not yet been assessed. Therefore, the main
      aim of the present study was to evaluate if an extract of commercial powdered
      seeds of Guarana could protect human dopaminergic neuroblastoma SH-SY5Y cell line
      against rotenone-induced cytotoxicity. Two concentration of Guarana
      dimethylsulfoxide extract (0.312 and 0.625 mg/mL) were added to SH-SY5Y cells
      treated with 300 nM rotenone for 48 h, and the cytoprotective effects were
      assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay, measuring lactate dehydrogenase (LDH) levels, and analyzing nuclear
      integrity with Hoechst33258 stain. Results showed that the addition of Guarana
      extract significantly increased the cell viability of SH-SY5Y cells treated with
      rotenone, in a dose-dependent manner. On the other hand, LDH levels were
      significantly reduced by addition of 0.312 mg/mL of Guarana, but unexpectedly, no
      changes were observed with the higher concentration. Moreover, chromatin
      condensation and nuclear fragmentation were significantly reduced by addition of
      any of both concentrations of the extract. The results obtained in this work
      could provide relevant information about the mechanisms underlying the
      degeneration of dopaminergic neurons in PD and precede in vivo experiments.
      Further studies are needed to investigate which active constituent is responsible
      for the cytoprotective effect produced by Paullinia cupana.

PMID- 21081704
TI  - Association between muscle mass, leg strength, and fat mass with physical
      function in older adults: influence of age and sex.
AB  - OBJECTIVE: The purposes of this study were to determine the relationship between
      muscle mass, muscle strength, muscle quality, and fat mass with a composite
      measure of physical function in older adults, and to determine whether these
      relations differed by age and sex. METHOD: Participants consisted of 1280 adults
      aged >= 55 yr from the NHANES study. Reduced rank regression was used to identify
      patterns of muscle mass, muscle strength, muscle quality, and fat mass related to
      physical function. RESULTS: A single relevant pattern emerged that included leg
      strength and fat mass as predictors of the 7 physical function variables. The leg
      strength loading was significantly greater than the fat mass loading in men and
      women aged 55-64 and >= 75, and differed between sexes. CONCLUSION: Leg strength
      and fat mass best predict physical function in older adults and the relative
      importance varies according to age and sex.

PMID- 21081705
TI  - The importance of PGC-1alpha in contractile activity-induced mitochondrial
      adaptations.
AB  - The transcriptional coactivator PPARgamma coactivator-1alpha (PGC-1alpha) is a
      critical regulator of mitochondrial content and function in skeletal muscle. PGC
      1alpha may also mediate mitochondrial adaptations in response to chronic
      contractile activity (CCA). To characterize the essential role of PGC-1alpha in
      organelle biogenesis, C2C12 murine myotubes were transfected with PGC-1alpha
      specific siRNA and subjected to electrical stimulation-evoked CCA. CCA enhanced
      cytochrome c oxidase (COX) activity along with increases in several nuclear
      encoded mitochondrial proteins. Transfection of PGC-1alpha siRNA decreased
      protein and mRNA of the coactivator by 60%, resulting in decrements of Tfam and
      COX-IV proteins. The mRNA expression of the PGC-1 family members PGC-1beta and
      PRC, as well as transcription factors NRF-1/2 and ERRalpha, did not exhibit
      compensatory changes in response to PGC-1alpha depletion. However,
      phosphorylation of AMPK was enhanced in myotubes with reduced levels of PGC
      1alpha. This suggests the presence of metabolic compensatory stress signals in
      cells deficient in PGC-1alpha. Our findings reveal that the CCA-induced increases
      in COX-IV protein and overall mitochondrial content, using both COX activity and
      organelle fluorescence, are dependent on PGC-1alpha. However, this was not the
      case for all proteins, since decreased levels of the coactivator did not
      attenuate the increases in Tfam and cytochrome c in response to CCA. These data
      indicate that PGC-1alpha is necessary for most of the mitochondrial adaptations
      that occur with CCA but that there are additional pathways that function in
      parallel with PGC-1alpha to mediate the elevated expression of specific nuclear
      encoded proteins that are vital for mitochondrial function and cell viability.

PMID- 21081706
TI  - Dipeptidyl peptidase IV inhibitor sitagliptin reduces local inflammation in
      adipose tissue and in pancreatic islets of obese mice.
AB  - Adipose tissue inflammation and reduced pancreatic beta-cell function are key
      issues in the development of cardiovascular disease and progressive metabolic
      dysfunction in type 2 diabetes mellitus. The aim of this study was to determine
      the effect of the DPP IV inhibitor sitagliptin on adipose tissue and pancreatic
      islet inflammation in a diet-induced obesity model. C57Bl/6J mice were placed on
      a high-fat (60% kcal fat) diet for 12 wk, with or without sitagliptin (4 g/kg) as
      a food admix. Sitagliptin significantly reduced fasting blood glucose by 21% as
      well as insulin by ~25%. Sitagliptin treatment reduced body weight without
      changes in overall body mass index or in the epididymal and retroperitoneal fat
      mass. However, sitagliptin treatment led to triple the number of small adipocytes
      despite reducing the number of the very large adipocytes. Sitagliptin
      significantly reduced inflammation in the adipose tissue and pancreatic islet.
      Macrophage infiltration in adipose tissue evaluated by immunostaining for Mac2
      was reduced by sitagliptin (P < 0.01), as was the percentage of CD11b+/F4/80+
      cells in the stromal vascular fraction (P < 0.02). Sitagliptin also reduced
      adipocyte mRNA expression of inflammatory genes, including IL-6, TNFalpha, IL
      12(p35), and IL-12(p40), 2.5- to fivefold as well as 12-lipoxygenase protein
      expression. Pancreatic islets were isolated from animals after treatments.
      Sitagliptin significantly reduced mRNA expression of the following inflammatory
      cytokines: MCP-1 (3.3-fold), IL-6 (2-fold), IL-12(p40) (2.2-fold), IL-12(p35) (5
      fold, P < 0.01), and IP-10 (2-fold). Collectively, the results indicate that
      sitagliptin has anti-inflammatory effects in adipose tissue and in pancreatic
      islets that accompany the insulinotropic effect.

PMID- 21081707
TI  - Relaxin counteracts the altered gastric motility of dystrophic (mdx) mice:
      functional and immunohistochemical evidence for the involvement of nitric oxide.
AB  - Impaired gastric motility ascribable to a defective nitric oxide (NO) production
      has been reported in dystrophic (mdx) mice. Since relaxin upregulates NO
      biosynthesis, its effects on the motor responses and NO synthase (NOS) expression
      in the gastric fundus of mdx mice were investigated. Mechanical responses of
      gastric strips were recorded via force displacement transducers. Evaluation of
      the three NOS isoforms was performed by immunohistochemistry and Western blot.
      Wild-type (WT) and mdx mice were distributed into three groups: untreated,
      relaxin pretreated, and vehicle pretreated. In strips from both untreated and
      vehicle-pretreated animals, electrical field stimulation (EFS) elicited
      contractile responses that were greater in mdx than in WT mice. In carbachol
      precontracted strips, EFS induced fast relaxant responses that had a lower
      amplitude in mdx than in WT mice. Only in the mdx mice did relaxin depress the
      amplitude of the neurally induced excitatory responses and increase that of the
      inhibitory ones. In the presence of L-NNA, relaxin was ineffective. In relaxin
      pretreated mdx mice, the amplitude of the EFS-induced contractile responses was
      decreased and that of the fast relaxant ones was increased compared with
      untreated mdx animals. Responses to methacholine or papaverine did not differ
      among preparations and were not influenced by relaxin. Immunohistochemistry and
      Western blotting showed a significant decrease in neuronal NOS expression and
      content in mdx compared with WT mice, which was recovered in the relaxin
      pretreated mdx mice. The results suggest that relaxin is able to counteract the
      altered contractile and relaxant responses in the gastric fundus of mdx mice by
      upregulating nNOS expression.

PMID- 21081709
TI  - Beyond the beers criteria: A comparative overview of explicit criteria.
AB  - OBJECTIVE: To provide a comparative overview of explicit criteria that have been
      developed since 2003 for inappropriate prescribing in older adults and to
      contrast these newer criteria with the most recent Beers criteria, published in
      2003. DATA SOURCES: MEDLINE and Google Scholar searches were performed from 2003
      through July 2010. Within MEDLINE, MeSH terms included aged, drug prescriptions,
      medication errors, and polypharmacy. Free-text search terms included elderly,
      guideline adherence, inappropriate prescribing, and medications. Related
      articles, as identified by MEDLINE, were used as well. Free-text search was
      performed on Google Scholar, using "potentially inappropriate prescribing
      elderly." Additional articles were identified in reference lists of key articles.
      STUDY SELECTION AND DATA EXTRACTION: Studies were selected if they were published
      after the most recent revision of the Beers criteria in 2003 and addressed the
      development and application of explicit criteria for the elderly. We
      independently reviewed pertinent literature to extract key information. DATA
      SYNTHESIS: The first explicit criteria published were the Beers criteria, and
      most research regarding inappropriate medication use applied these criteria.
      Criteria developed subsequent to the Beers criteria include the French Consensus
      Panel list, STOPP (Screening Tool of Older Persons' Prescription) and START
      (Screening Tool to Alert doctors to Right Treatment), the Australian Prescribing
      Indicators tool, and the Norwegian General Practice Criteria. Newer criteria
      offer several improvements on the Beers criteria, namely drug-drug interactions,
      omission of potentially beneficial therapy, and more broadly applicable criteria
      across international borders. CONCLUSIONS: Although no criteria may ever be
      globally applicable, STOPP and START make significant advances. Regional drug
      availability, economic considerations, and clinical practice patterns impact
      criteria selection. Research to validate the several newer criteria in various
      practice settings and to explore the effect of adhering to the guidelines on
      patient outcomes is warranted. Data from such research will aid practitioners in
      identifying preferred criteria.

PMID- 21081708
TI  - Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2
      gene expression by Sirt1 and FoxO1.
AB  - Protein deacetylase Sirt1 has been implicated in the regulation of hepatic
      gluconeogenesis; however, the mechanisms are not fully understood. To further
      elucidate how Sirt1 regulates gluconeogenesis, we took a loss-of-function
      approach by deleting the coding DNA sequence for the catalytic domain of the
      Sirt1 gene in the liver of a wild-type mouse (LKO(Sirt)1) or a genetic diabetic
      mouse in which hepatic insulin receptor substrates 1 and 2 are deleted
      (DKO(Irs1/2)). Whereas LKO(Sirt)1 mice exhibited normal levels of fasting and fed
      blood glucose, inactivation of Sirt1 in DKO(Irs1/2) mice (TKO(Irs1/2:Sirt)1)
      reduced blood glucose levels and moderately improved systemic glucose tolerance.
      Pyruvate tolerance was also significantly improved in TKO(Irs1/2:Sirt)1 mice,
      suggesting that Sirt1 promotes hepatic gluconeogenesis in this diabetic mouse
      model. To understand why inactivation of hepatic Sirt1 does not alter blood
      glucose levels in the wild-type background, we searched for a potential cause and
      found that expression of small heterodimer partner (SHP, encoded by the Nr0b2
      gene), an orphan nuclear receptor, which has been shown to suppress the activity
      of forkhead transcription factor FoxO1, was decreased in the liver of LKO(Sirt)1
      mice. Furthermore, our luciferase reporter assays and chromatin
      immunoprecipitation analysis revealed that the Nr0b2 gene is a target of FoxO1,
      which is also regulated by Sirt1. After the gene is upregulated, Nr0b2 can feed
      back and repress FoxO1- and Sirt1-activated G6pc and Pdk4 gene expression. Thus,
      our results suggest that Sirt1 can both positively and negatively regulate
      hepatic gluconeogenesis through FoxO1 and Nr0b2 and keep this physiological
      process in control.

PMID- 21081710
TI  - Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus.
AB  - OBJECTIVE: To review the efficacy, safety, dosing, drug interactions, as well as
      economic and therapeutic considerations of belimumab, an investigational B
      lymphocyte stimulator (BLyS) inhibitor. DATA SOURCES: A systematic, English
      language MEDLINE search (1966-August 2010) was conducted using the search terms
      belimumab, Benlysta, B-lymphocyte stimulators, BLyS-specific inhibitors, and
      systemic lupus erythematosus (SLE). Press releases and bibliographies were
      reviewed for additional information and citations. STUDY SELECTION AND DATA
      EXTRACTION: Belimumab was first identified and studied as a human protein target
      in 1999. Therefore, all published clinical trials and abstracts evaluating the
      safety and efficacy of belimumab for treatment of SLE as well as review articles
      from 1999 to present were evaluated for inclusion. Additional data were extracted
      from the manufacturer's Web site and Food and Drug Administration (FDA)
      documents. DATA SYNTHESIS: Current therapies for SLE target nonspecific sites for
      inflammatory reduction and immune system suppression. Belimumab is a target
      specific, human IgG1lambda monoclonal B-lymphocyte stimulator inhibitor currently
      in late stage investigation for the treatment of SLE. Unpublished Phase 3 trials
      have reported statistically significant results for primary endpoints when
      belimumab 10 mg/kg plus standard of care was compared to placebo plus standard of
      care in seropositive patients with SLE. Overall, belimumab has been relatively
      well tolerated with discontinuation rates and adverse events similar to those of
      placebo. If belimumab is approved by the FDA, its US market launch would be
      expected in 2011. CONCLUSIONS: Belimumab has shown significant benefits for
      patients with SLE in the few Phase 3 trials that have been published. However,
      questions remain regarding optimal patient population, duration of treatment,
      place in therapy, and long-term adverse effects.

PMID- 21081711
TI  - Development and validation of a new, sensitive immunochemical assay for O6
      methylguanine in DNA and its application in a population study.
AB  - BACKGROUND: Investigations of the presence of the precarcinogenic DNA adduct O6
      methylguanine (O6-meG) in humans and its association with exposure or cancer risk
      have been hindered by the absence of analytic methods of adequate sensitivity and
      throughput. We report the development, validation, and application of an ELISA
      type assay for O6-meG appropriate for large-scale population studies. METHODS: In
      the new analytic method, restriction enzymes are used to digest DNA to fragments
      of size expected to contain no more than one O6-meG residue. Anti-adduct antisera
      are used to transfer O6-meG-containing fragments to a solid surface, where they
      are detected using anti-ssDNA antisera, the high ratio of normal nucleotides to
      adducts providing a strong signal enhancement. RESULTS: An assay with a limit of
      detection of 1.5 adducts/109 nucleotides using 10 MUg of DNA, a dynamic range of
      approximately two orders of magnitude and satisfactory precision and accuracy
      characteristics was established and validated. Analysis of samples from 120
      subjects from the Rhea mother-child cohort in Crete led to the detection of O6
      meG in 70% of maternal and 50% of cord blood buffy coat samples at mean levels of
      0.65 and 0.38 adducts/108 nucleotides, respectively. CONCLUSIONS: The frequent
      observation of O6-meG in human DNA is compatible with dietary compounds (e.g. N
      nitroso compounds or their precursors), or endogenous processes being responsible
      for the formation of this adduct. IMPACT: The new assay opens the way for large
      scale population studies of O6-meG as a biomarker of exposure or risk. The
      approach used in this assay can, in principle, be extended to any DNA adduct for
      which suitable antisera are available.

PMID- 21081712
TI  - Genome-wide characterization of centromeric satellites from multiple mammalian
      genomes.
AB  - Despite its importance in cell biology and evolution, the centromere has remained
      the final frontier in genome assembly and annotation due to its complex repeat
      structure. However, isolation and characterization of the centromeric repeats
      from newly sequenced species are necessary for a complete understanding of genome
      evolution and function. In recent years, various genomes have been sequenced, but
      the characterization of the corresponding centromeric DNA has lagged behind.
      Here, we present a computational method (RepeatNet) to systematically identify
      higher-order repeat structures from unassembled whole-genome shotgun sequence and
      test whether these sequence elements correspond to functional centromeric
      sequences. We analyzed genome datasets from six species of mammals representing
      the diversity of the mammalian lineage, namely, horse, dog, elephant, armadillo,
      opossum, and platypus. We define candidate monomer satellite repeats and
      demonstrate centromeric localization for five of the six genomes. Our analysis
      revealed the greatest diversity of centromeric sequences in horse and dog in
      contrast to elephant and armadillo, which showed high-centromeric sequence
      homogeneity. We could not isolate centromeric sequences within the platypus
      genome, suggesting that centromeres in platypus are not enriched in satellite
      DNA. Our method can be applied to the characterization of thousands of other
      vertebrate genomes anticipated for sequencing in the near future, providing an
      important tool for annotation of centromeres.

PMID- 21081713
TI  - Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic
      activity against human multiple myeloma.
AB  - Activation of the adaptive Ire1-XBP1 pathway has been identified in many solid
      tumors and hematologic malignancies, including multiple myeloma (MM). Here, we
      report the identification of STF-083010, a novel small-molecule inhibitor of
      Ire1. STF-083010 inhibited Ire1 endonuclease activity, without affecting its
      kinase activity, after endoplasmic reticulum stress both in vitro and in vivo.
      Treatment with STF-083010 showed significant antimyeloma activity in model human
      MM xenografts. Similarly, STF-083010 was preferentially toxic to freshly isolated
      human CD138(+) MM cells compared with other similarly isolated cell populations.
      The identification of this novel Ire1 inhibitor supports the hypothesis that the
      Ire1-XBP1 axis is a promising target for anticancer therapy, especially in the
      context of MM.

PMID- 21081715
TI  - The cover. Temples and bathing ghat at Benares.

PMID- 21081716
TI  - A piece of my mind. Secret shopper.

PMID- 21081717
TI  - Frances Kelsey honored for FDA legacy: award notes her work on thalidomide,
      clinical trials.

PMID- 21081714
TI  - Contemporary diagnostic imaging modalities for the staging and surveillance of
      melanoma patients: a meta-analysis.
AB  - BACKGROUND: Meta-analyses were performed to examine the utility of
      ultrasonography, computed tomography (CT), positron emission tomography (PET),
      and a combination of both (PET-CT) for the staging and surveillance of melanoma
      patients. METHOD: Patient-level data from 74 studies containing 10,528 patients
      (between January 1, 1990, and June, 30, 2009) were used to derive characteristics
      of the diagnostic tests used. Meta-analyses were conducted by use of Bayesian
      bivariate binomial models to estimate sensitivity and specificity. Diagnostic
      odds ratios [ie, true-positive results/false-negative results)/(false-positive
      results/true-negative results)] and their 95% credible intervals (CrIs) and
      positive predictive values were used as indicators of test performance. RESULTS:
      Among the four imaging methods examined for the staging of regional lymph nodes,
      ultrasonography had the highest sensitivity (60%, 95% CrI = 33% to 83%),
      specificity (97%, 95% CrI = 88% to 99%), and diagnostic odds ratio (42, 95% CrI =
      8.08 to 249.8). For staging of distant metastases, PET-CT had the highest
      sensitivity (80%, 95% CrI = 53% to 93%), specificity (87%, 95% CrI = 54% to 97%),
      and diagnostic odds ratio (25, 95% CrI = 3.58 to 198.7). Similar trends were
      observed for melanoma surveillance of lymph node involvement, with
      ultrasonography having the highest sensitivity (96%, 95% CrI = 85% to 99%),
      specificity (99%, 95% CrI = 95% to 100%), and diagnostic odds ratio (1675, 95%
      CrI = 226.6 to 15,920). For distant metastases, PET-CT had the highest
      sensitivity (86%, 95% CrI = 76% to 93%), specificity (91%, 95% CrI = 79% to 97%),
      and diagnostic odds ratio (67, 95% CrI = 20.42 to 229.7). Positive predictive
      values were likewise highest for ultrasonography in lymph node staging and for
      PET-CT in detecting distant metastases. CONCLUSION: Among the compared
      modalities, ultrasonography was superior for detecting lymph node metastases, and
      PET-CT was superior for the detection of distant metastases in both the staging
      and surveillance of melanoma patients.

PMID- 21081718
TI  - FDA warning targets OTC chelation products.

PMID- 21081719
TI  - Prolonged bisphosphonate use linked to rare fractures, esophageal cancer.

PMID- 21081720
TI  - Treating sternal wound infections after cardiac surgery with an implantable
      gentamicin-collagen sponge.

PMID- 21081721
TI  - Treating sternal wound infections after cardiac surgery with an implantable
      gentamicin-collagen sponge.

PMID- 21081722
TI  - Diagnosing delirium.

PMID- 21081723
TI  - Diagnosing delirium.

PMID- 21081724
TI  - Diagnosing delirium.

PMID- 21081725
TI  - Importance of blinding in randomized trials.

PMID- 21081726
TI  - Diagnosing influenza.

PMID- 21081727
TI  - Infection with transmissible strains of Pseudomonas aeruginosa and clinical
      outcomes in adults with cystic fibrosis.
AB  - CONTEXT: Studies from Australia and the United Kingdom have shown that some
      patients with cystic fibrosis are infected with common transmissible strains of
      Pseudomonas aeruginosa. OBJECTIVES: To determine the prevalence and incidence of
      infection with transmissible strains of P. aeruginosa and whether presence of the
      organism was associated with adverse clinical outcomes in Canada. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective observational cohort study of adult
      patients cared for at cystic fibrosis clinics in Ontario, Canada, with enrollment
      from September 2005 to September 2008. Sputum was collected at baseline, 3
      months, and yearly thereafter for 3 years; and retrieved P. aeruginosa isolates
      were genotyped. Vital status (death or lung transplant) was assessed for all
      enrolled patients until December 31, 2009. MAIN OUTCOME MEASURES: Incidence and
      prevalence of P. aeruginosa isolation, rates of decline in lung function, and
      time to death or lung transplantation. RESULTS: Of the 446 patients with cystic
      fibrosis studied, 102 were discovered to be infected with 1 of 2 common
      transmissible strains of P. aeruginosa at study entry. Sixty-seven patients were
      infected with strain A (15%), 32 were infected with strain B (7%), and 3 were
      simultaneously infected with both strains (0.6%). Strain A was found to be
      genetically identical to the Liverpool epidemic strain but strain B has not been
      previously described as an epidemic strain. The incidence rate of new infections
      with these 2 transmissible strains was relatively low (7.0 per 1000 person-years;
      95% confidence interval [CI], 1.8-12.2 per 1000 person-years). Compared with
      patients infected with unique strains of P. aeruginosa, patients infected with
      the Liverpool epidemic strain (strain A) and strain B had similar declines in
      lung function (difference in decline in percent predicted forced expiratory
      volume in the first second of expiration of 0.64% per year [95% CI, -1.52% to
      2.80% per year] and 1.66% per year [95% CI, -1.00% to 4.30%], respectively).
      However, the 3-year rate of death or lung transplantation was greater in those
      infected with the Liverpool epidemic strain (18.6%) compared with those infected
      with unique strains (8.7%) (adjusted hazard ratio, 3.26 [95% CI, 1.41 to 7.54]; P
      = .01). CONCLUSIONS: A common strain of P. aeruginosa (Liverpool epidemic
      strain/strain A) infects patients with cystic fibrosis in Canada and the United
      Kingdom. Infection with this strain in adult Canadian patients with cystic
      fibrosis was associated with a greater risk of death or lung transplantation.

PMID- 21081728
TI  - Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced
      hepatocellular carcinoma: a randomized trial.
AB  - CONTEXT: In a randomized phase 3 trial, 400 mg of sorafenib twice daily prolonged
      overall survival of patients with advanced hepatocellular carcinoma (HCC) and
      Child-Pugh A disease. In a phase 1 study, sorafenib combined with doxorubicin, 60
      mg/m(2), was well tolerated by patients with refractory solid tumors. The
      combination of sorafenib and doxorubicin in patients with advanced HCC has not
      been evaluated in a phase 2 or 3 trial. OBJECTIVE: To evaluate the efficacy and
      safety of doxorubicin plus sorafenib compared with doxorubicin alone in patients
      with advanced HCC and Child-Pugh A disease. DESIGN, SETTING, AND PATIENTS: In a
      double-blind phase 2 multinational study, conducted from April 2005 to October
      2006, 96 patients (76% male; median age, 65 years [range, 38-82 years]) with
      advanced HCC, Eastern Cooperative Oncology Group performance status 0 to 2, Child
      Pugh A status, and no prior systemic therapy were randomly assigned to receive 60
      mg/m(2) of doxorubicin intravenously every 21 days plus either 400 mg of
      sorafenib or placebo orally twice a day. The date of the last patient's follow-up
      was April 2008. MAIN OUTCOME MEASURE: Time to progression as determined by
      independent review. RESULTS: Following complete accrual, an unplanned early
      analysis for efficacy was performed by the independent data monitoring committee,
      so the trial was halted. The 2 patients remaining in the placebo group at that
      time were offered sorafenib. Based on 51 progressions, 63 deaths, and 70 events
      for progression-free survival, median time to progression was 6.4 months in the
      sorafenib-doxorubicin group (95% confidence interval [CI], 4.8-9.2), and 2.8
      months (95% CI, 1.6-5) in the doxorubicin-placebo monotherapy group (P = .02).
      Median overall survival was 13.7 months (95% CI, 8.9--not reached) and 6.5 months
      (95% CI, 4.5-9.9; P = .006), and progression-free survival was 6.0 months (95%
      CI, 4.6-8.6) and 2.7 months (95% CI, 1.4-2.8) in these groups, respectively (P =
      .006). Toxicity profiles were similar to those for the single agents.
      CONCLUSIONS: Among patients with advanced HCC, treatment with sorafenib plus
      doxorubicin compared with doxorubicin monotherapy resulted in greater median time
      to progression, overall survival, and progression-free survival. The degree to
      which this improvement may represent synergism between sorafenib and doxorubicin
      remains to be defined. The combination of sorafenib and doxorubicin is not yet
      indicated for routine clinical use. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00108953.

PMID- 21081729
TI  - Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media
      in children: a systematic review.
AB  - CONTEXT: Acute otitis media (AOM) is the most common condition for which
      antibiotics are prescribed for US children; however, wide variation exists in
      diagnosis and treatment. OBJECTIVES: To perform a systematic review on AOM
      diagnosis, treatment, and the association of heptavalent pneumococcal conjugate
      vaccine (PCV7) use with AOM microbiology. DATA SOURCES: PubMed, Cochrane
      Databases, and Web of Science, searched to identify articles published from
      January 1999 through July 2010. STUDY SELECTION: Diagnostic studies with a
      criterion standard, observational studies and randomized controlled trials
      comparing AOM microbiology with and without PCV7, and randomized controlled
      trials assessing antibiotic treatment. DATA EXTRACTION: Independent article
      review and study quality assessment by 2 investigators with consensus resolution
      of discrepancies. RESULTS: Of 8945 citations screened, 135 were included. Meta
      analysis was performed for comparisons with 3 or more trials. Few studies
      examined diagnosis; otoscopic findings of tympanic membrane bulging (positive
      likelihood ratio, 51 [95% confidence interval {CI}, 36-73]) and redness (positive
      likelihood ratio, 8.4 [95% CI, 7-11]) were associated with accurate diagnosis. In
      the few available studies, prevalence of Streptococcus pneumoniae decreased (eg,
      33%-48% vs 23%-31% of AOM isolates), while that of Haemophilus influenzae
      increased (41%-43% vs 56%-57%) pre- vs post-PCV7. Short-term clinical success was
      higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%;
      pooled rate difference, 12% [95% CI, 5%-18%]; number needed to treat, 9 [95% CI,
      6-20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4
      studies showed greater clinical success for immediate vs delayed antibiotics (95%
      vs 80%; rate difference, 15% [95% CI, 6%-24%] and 86% vs 70%; rate difference,
      16% [95% CI, 6%-26%]). Data are absent on long-term effects on antimicrobial
      resistance. Meta-analyses in general showed no significant differences in
      antibiotic comparative effectiveness. CONCLUSIONS: Otoscopic findings are
      critical to accurate AOM diagnosis. AOM microbiology has changed with use of
      PCV7. Antibiotics are modestly more effective than no treatment but cause adverse
      effects in 4% to 10% of children. Most antibiotics have comparable clinical
      success.

PMID- 21081730
TI  - Discussing radiation risks associated with CT scans with patients.

PMID- 21081731
TI  - Accelerated approval and possible withdrawal of midodrine.

PMID- 21081732
TI  - Risk of kava hepatotoxicity and the FDA consumer advisory.

PMID- 21081733
TI  - Health systems strengthening mechanism for the Global Health Initiative.

PMID- 21081734
TI  - JAMA patient page. Acute otitis media.

PMID- 21081735
TI  - Isolated primary cardiac sarcoidosis: MRI diagnosis and monitoring of treatment
      response with cardiac enzymes.

PMID- 21081736
TI  - Letter by Hobai regarding article, "Long-term anabolic-androgenic steroid use is
      associated with left ventricular dysfunction".

PMID- 21081737
TI  - Letter by Lowenthal et al regarding article, "BNP levels predict outcome in
      pediatric heart failure patients: post hoc analysis of the Pediatric Carvedilol
      Trial".

PMID- 21081738
TI  - Unforeseen consequences of therapy with continuous-flow pumps.

PMID- 21081739
TI  - Mind-body medicine in chronic heart failure: a translational science challenge.

PMID- 21081740
TI  - Renal function, health outcomes, and resource utilization in acute heart failure:
      a systematic review.

PMID- 21081741
TI  - In vivo 3D distribution of lipid-core plaque in human coronary artery as assessed
      by fusion of near infrared spectroscopy-intravascular ultrasound and multislice
      computed tomography scan.

PMID- 21081742
TI  - Paying at the pump: diet-induced accumulation of cardiac lipid and systolic
      dysfunction.

PMID- 21081744
TI  - Four-dimensional flow magnetic resonance imaging with wall shear stress analysis
      before and after repair of aortopulmonary fistula.

PMID- 21081743
TI  - Imaging phenotype vs genotype in nonhypertrophic heritable cardiomyopathies:
      dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy.

PMID- 21081745
TI  - Emphasizing the burden of proof: The American College of Cardiology 2008 Expert
      Panel Comments on the ENHANCE Trial.

PMID- 21081746
TI  - Myocardial infarction outcomes: "the times, they are a-changin...".

PMID- 21081747
TI  - Hospital specialization for coronary artery bypass grafting: anything special
      about it?

PMID- 21081749
TI  - Technical feasibility of an online decision support system for acute coronary
      syndromes.

PMID- 21081748
TI  - Variation in recovery: Role of gender on outcomes of young AMI patients (VIRGO)
      study design.
AB  - BACKGROUND: Among individuals with ischemic heart disease, young women with an
      acute myocardial infarction (AMI) represent an extreme phenotype associated with
      an excess mortality risk. Although women younger than 55 years of age account for
      less than 5% of hospitalized AMI events, almost 16 000 deaths are reported
      annually in this group, making heart disease a leading killer of young women.
      Despite a higher risk of mortality compared with similarly aged men, young women
      have been the subject of few studies. METHODS AND RESULTS: Variation in Recovery:
      Role of Gender on Outcomes of Young AMI Patients (VIRGO) is a large,
      observational study of the presentation, treatment, and outcomes of young women
      and men with AMI. VIRGO will enroll 2000 women, 18 to 55 years of age, with AMI
      and a comparison cohort of 1000 men with AMI from more than 100 participating
      hospitals. The aims of the study are to determine sex differences in the
      distribution and prognostic importance of biological, demographic, clinical, and
      psychosocial risk factors; to determine whether there are sex differences in the
      quality of care received by young AMI patients; and to determine how these
      factors contribute to sex differences in outcomes (including mortality,
      hospitalization, and health status). Blood serum and DNA for consenting
      participants will be stored for future studies. CONCLUSIONS: VIRGO will seek to
      identify novel and prognostic factors that contribute to outcomes in this young
      AMI population. Results from the study will be used to develop clinically useful
      risk-stratification models for young AMI patients, explain sex differences in
      outcomes, and identify targets for intervention.

PMID- 21081750
TI  - Lifetime risk of acute myocardial infarction in Japan.

PMID- 21081751
TI  - Three questions for evidence-based cardiac electrophysiology.

PMID- 21081752
TI  - Calcium signaling by STIM and Orai: intimate coupling details revealed.
AB  - STIM (stromal interaction molecule) and Orai, two recently identified protein
      families, mediate cellular Ca(2+) signals through a remarkably dynamic
      interaction. STIM proteins are sensors of Ca(2+) stored within the endoplasmic
      reticulum (ER). Orai proteins are highly selective plasma membrane (PM) channels
      that allow only Ca(2+) ions to flow into cells. Although present in separate
      membranes, the two proteins undergo profound reorganization culminating in an
      exquisite pas de deux within small junctional regions between the ER and PM.
      Before these proteins can embrace, STIM undergoes an activation process triggered
      by depletion of Ca(2+) stores. During its union with Orai, STIM induces the
      channel pore within Orai to open, allowing Ca(2+) ions to flow through the PM and
      provide crucial intracellular signals. Recent studies on the activation of STIM
      and its coupling to Orai provide valuable new insights into the nature of the
      liaison between these two proteins and the intricate mechanism through which
      activation of Ca(2+) signals occurs.

PMID- 21081753
TI  - Frizzled signaling: Galphao and Rab5 at the crossroads of the canonical and PCP
      pathways?
AB  - Endocytosis modulates the activities of members of a family of receptors known as
      Frizzled (Fz) proteins, which control canonical beta-catenin signaling and the
      planar cell polarity pathway; however, what determines which of the two pathways
      is activated is unclear. Evidence now suggests that the guanosine triphosphatase
      Rab5, a key regulator of endocytosis, binds directly to Fz proteins and that
      subsequent trafficking steps determine the outcome of Fz signaling.

PMID- 21081754
TI  - Activation of STIM1-Orai1 involves an intramolecular switching mechanism.
AB  - Stromal interaction molecule 1 (STIM1) stimulates calcium ion (Ca(2+)) entry
      through plasma membrane Orai1 channels in response to decreased Ca(2+)
      concentrations in the endoplasmic reticulum lumen. We identified an acidic motif
      within the STIM1 coiled-coil region that keeps its Ca(2+) activation domain
      [Ca(2+) release-activated Ca(2+) (CRAC) activation domain/STIM1-Orai activating
      region (CAD/SOAR)]-a cytoplasmic region required for its activation of Orai1
      inactive. The sequence of the STIM1 acidic motif shows substantial similarity to
      that of the carboxyl-terminal coiled-coil segment of Orai1, which is the
      postulated site of interaction with STIM1. Mutations within this acidic region
      rendered STIM1 constitutively active, whereas mutations within a short basic
      segment of CAD/SOAR prevented Orai1 activation. We propose that the CAD/SOAR
      domain is released from an intramolecular clamp during STIM1 activation, allowing
      the basic segment to activate Orai1 channels. This evolutionarily conserved
      mechanism of STIM1 activation resembles the regulation of protein kinases by
      intramolecular silencing through pseudosubstrate binding.

PMID- 21081755
TI  - Solution of the structure of the TNF-TNFR2 complex.
AB  - Tumor necrosis factor (TNF) is an inflammatory cytokine that has important roles
      in various immune responses, which are mediated through its two receptors, TNF
      receptor 1 (TNFR1) and TNFR2. Antibody-based therapy against TNF is used
      clinically to treat several chronic autoimmune diseases; however, such treatment
      sometimes results in serious side effects, which are thought to be caused by the
      blocking of signals from both TNFRs. Therefore, knowledge of the structural basis
      for the recognition of TNF by each receptor would be invaluable in designing TNFR
      selective drugs. Here, we solved the 3.0 angstrom resolution structure of the TNF
      TNFR2 complex, which provided insight into the molecular recognition of TNF by
      TNFR2. Comparison to the known TNFR1 structure highlighted several differences
      between the ligand-binding interfaces of the two receptors. Additionally, we also
      demonstrated that TNF-TNFR2 formed aggregates on the surface of cells, which may
      be required for signal initiation. These results may contribute to the design of
      therapeutics for autoimmune diseases.

PMID- 21081757
TI  - Hexavalent chromium in Texas drinking water.

PMID- 21081756
TI  - Mitochondrially targeted ceramides preferentially promote autophagy, retard cell
      growth, and induce apoptosis.
AB  - C(6)-pyridinium (D-erythro-2-N-[6'-(1''-pyridinium)-hexanoyl]sphingosine bromide
      [LCL29]) is a cationic mitochondrion-targeting ceramide analog that promotes
      mitochondrial permeabilization and cancer cell death. In this study, we compared
      the biological effects of that compound with those of D-erythro-C(6)-ceramide,
      its non-mitochondrion-targeting analog. In MCF7 cells it was found that C(6)
      pyridinium ceramide preferentially promoted autophagosome formation and retarded
      cell growth more extensively than its uncharged analog. This preferential
      inhibition of cell growth was also observed in breast epithelial cells and other
      breast cancer cells. In addition, this compound could promote Bax translocation
      to mitochondria. This redistribution of Bax in MCF7 cells could be blocked by the
      pan-caspase inhibitor zVAD-fmk but via a Bid-independent signaling pathway.
      Moreover, C(6)-pyridinium ceramide-induced translocation of Bax to mitochondria
      led to mitochondrial permeabilization and cell death. Overall, we show that
      mitochondrial targeting of C(6)-pyridinium ceramide significantly enhances
      cellular response to this compound.

PMID- 21081759
TI  - Degradation of fibrinogen and collagen by staphopains, cysteine proteases
      released from Staphylococcus aureus.
AB  - Staphylococcus aureus is the most frequently isolated pathogen in gram-positive
      sepsis often complicated by a blood clotting disorder, and is the leading cause
      of infective endocarditis induced by bacterial destruction of endocardial
      tissues. The bacterium secretes cysteine proteases referred to as staphopain A
      (ScpA) and staphopain B (SspB). To investigate virulence activities of
      staphopains pertinent to clotting disorders and tissue destruction, we examined
      their effects on collagen, one of the major tissue components, and on plasma
      clotting. Both staphopains prolonged the partial thromboplastin time of plasma in
      a dose- and activity-dependent manner, with SspB being threefold more potent than
      ScpA. Staphopains also prolonged the thrombin time of both plasma and fibrinogen,
      indicating that these enzymes can cause impaired plasma clotting through
      fibrinogen degradation. Whereas SspB cleaved the fibrinogen Aalpha-chain at the C
      terminal region very efficiently, ScpA degraded it rather slowly. This explains
      the superior ability of the former enzyme to impair fibrinogen clottability.
      Enzymically active staphopains, at concentrations as low as 10 nM, degraded
      collagen with comparable efficiency. These results show novel virulence
      activities of staphopains in degrading fibrinogen and collagen, and suggest an
      involvement of staphopains in the clotting impairment and tissue destruction
      caused by staphylococcal infection.

PMID- 21081758
TI  - Prevalence, conservation and functional analysis of Yersinia and Escherichia
      CRISPR regions in clinical Pseudomonas aeruginosa isolates.
AB  - Here, we report the characterization of 122 Pseudomonas aeruginosa clinical
      isolates from three distinct geographical locations: Dartmouth Hitchcock Medical
      Center in New Hampshire, USA, the Charles T. Campbell Eye Microbiology Lab at the
      University of Pittsburgh Medical Center, USA, and the Aravind Eye Hospital in
      Madurai, India. We identified and located clustered regularly interspaced short
      palindromic repeats (CRISPR) in 45/122 clinical isolates and sequenced these
      CRISPR, finding that Yersinia subtype CRISPR regions (33 %) were more prevalent
      than the Escherichia CRISPR region subtype (6 %) in these P. aeruginosa clinical
      isolates. Further, we observed 132 unique spacers from these 45 CRISPR that are
      100 % identical to prophages or sequenced temperate bacteriophage capable of
      becoming prophages. Most intriguingly, all of these 132 viral spacers matched to
      temperate bacteriophage/prophages capable of inserting into the host chromosome,
      but not to extrachromosomally replicating lytic P. aeruginosa bacteriophage. We
      next assessed the ability of the more prevalent Yersinia subtype CRISPR regions
      to mediate resistance to bacteriophage infection or lysogeny by deleting the
      entire CRISPR region from sequenced strain UCBPP-PA14 and six clinical isolates.
      We found no change in CRISPR-mediated resistance to bacteriophage infection or
      lysogeny rate even for CRISPR with spacers 100 % identical to a region of the
      infecting bacteriophage. Lastly, to show these CRISPR and cas genes were
      expressed and functional, we demonstrated production of small CRISPR RNAs. This
      work provides both the first examination to our knowledge of CRISPR regions
      within clinical P. aeruginosa isolates and a collection of defined CRISPR
      positive and -negative strains for further CRISPR and cas gene studies.

PMID- 21081760
TI  - Induction of cell death after localization to the host cell mitochondria by the
      Mycobacterium tuberculosis PE_PGRS33 protein.
AB  - PE_PGRS33 is the most studied member of the unique PE family of mycobacterial
      proteins. These proteins are composed of a PE domain (Pro-Glu motif), a linker
      region and a PGRS domain (polymorphic GC-rich-repetitive sequence). Previous
      studies have shown that PE_PGRS33 is surface-exposed, constitutively expressed
      during growth and infection, involved in creating antigenic diversity, and able
      to induce death in transfected or infected eukaryotic cells. In this study, we
      showed that PE_PGRS33 co-localizes to the mitochondria of transfected cells, a
      phenomenon dependent on the linker region and the PGRS domain, but not the PE
      domain. Using different genetic fusions and chimeras, we also demonstrated a
      direct correlation between localization to the host mitochondria and the
      induction of cell death. Finally, although all constructs localizing to the
      mitochondria did induce apoptosis, only the wild-type PE_PGRS33 with its own PE
      domain also induced primary necrosis, indicating a potentially important role for
      the PE domain. Considering the importance of primary necrosis in Mycobacterium
      tuberculosis dissemination during natural infection, the PE_PGRS33 protein may
      play a crucial role in the pathogenesis of tuberculosis.

PMID- 21081761
TI  - Identification of novel diphenyl urea inhibitors of Mt-GuaB2 active against
      Mycobacterium tuberculosis.
AB  - In contrast with most bacteria, which harbour a single inosine monophosphate
      dehydrogenase (IMPDH) gene, the genomic sequence of Mycobacterium tuberculosis
      H37Rv predicts three genes encoding IMPDH: guaB1, guaB2 and guaB3. These three
      genes were cloned and expressed in Escherichia coli to evaluate functional IMPDH
      activity. Purified recombinant Mt-GuaB2, which uses inosine monophosphate as a
      substrate, was identified as the only active GuaB orthologue in M. tuberculosis
      and showed optimal activity at pH 8.5 and 37  degrees C. Mt-GuaB2 was inhibited
      significantly in vitro by a panel of diphenyl urea-based derivatives, which were
      also potent anti-mycobacterial agents against M. tuberculosis and Mycobacterium
      smegmatis, with MICs in the range of 0.2-0.5 MUg ml(-1). When Mt-GuaB2 was
      overexpressed on a plasmid in trans in M. smegmatis, a diphenyl urea analogue
      showed a 16-fold increase in MIC. Interestingly, when Mt-GuaB orthologues (Mt
      GuaB1 and 3) were also overexpressed on a plasmid in trans in M. smegmatis, they
      also conferred resistance, suggesting that although these Mt-GuaB orthologues
      were inactive in vitro, they presumably titrate the effect of the inhibitory
      properties of the active compounds in vivo.

PMID- 21081763
TI  - Exploring the bZIP transcription factor regulatory network in Neurospora crassa.
AB  - Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic
      organisms, including filamentous fungi such as Neurospora crassa. The 178
      predicted DNA-binding TFs in N. crassa are distributed primarily among six gene
      families, which represent an ancient expansion in filamentous ascomycete genomes;
      98 TF genes show detectable expression levels during vegetative growth of N.
      crassa, including 35 that show a significant difference in expression level
      between hyphae at the periphery versus hyphae in the interior of a colony.
      Regulatory networks within a species genome include paralogous TFs and their
      respective target genes (TF regulon). To investigate TF network evolution in N.
      crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains
      nine members. We performed baseline transcriptional profiling during vegetative
      growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We
      further characterized the regulatory network of one member of the bZIP family,
      NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in
      resistance to multiple stress responses, including oxidative and heavy metal
      stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated
      with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like
      regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans
      and Aspergillus fumigatus showed both conservation and divergence. These data
      indicate how N. crassa responds to stress and provide information on pathway
      evolution.

PMID- 21081764
TI  - Gabapentin improves postcesarean delivery pain management: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: Gabapentin is effective for preventing and treating acute and chronic
      postoperative pain; however, it has not been described for use in cesarean
      delivery. We hypothesized that preoperative gabapentin would reduce postcesarean
      delivery pain. METHODS: Women undergoing scheduled cesarean delivery were
      randomized to receive preoperative gabapentin 600 mg, or placebo. Spinal
      anesthesia was achieved with 0.75% hyperbaric bupivacaine 12 mg, fentanyl 10 MUg,
      and morphine 100 MUg. Postoperative analgesia was initiated with intraoperative
      ketorolac and acetaminophen, and continued with postoperative diclofenac,
      acetaminophen, and morphine. Patients were assessed at 6, 12, 24, and 48 hours
      after spinal anesthesia for pain at rest and on movement using a visual analog
      scale (0 to 100 mm), satisfaction, opioid consumption, and side effects. Neonatal
      interventions, Apgar scores, umbilical artery blood gases, and breastfeeding
      difficulties were assessed. Chronic pain was assessed 3 months after delivery.
      Maternal and umbilical vein gabapentin plasma concentrations were measured in a
      subgroup of patients. Mixed-model analysis was used to compare the primary
      outcome of visual analog scale pain scores at 24 hours between groups. RESULTS:
      Forty-six patients were randomized, and 2 were excluded from analysis. The mean
      (95% confidence interval, CI) pain scores on movement at 24 hours were 21 mm (CI
      = 13-28) in the gabapentin and 41 mm (CI = 31-50) in the placebo group (P =
      0.001). Maternal satisfaction was higher in the gabapentin group. There was no
      difference in opioid consumption. Severe maternal sedation was more common in the
      gabapentin group (19% vs. 0%, P = 0.04). There was no difference in neonatal
      Apgar scores, interventions, or umbilical artery pH. The mean (SD) maternal
      vein:umbilical vein plasma gabapentin ratio was 0.86 (0.12). The incidence of
      pain at 3 months was similar in both groups. CONCLUSION: Preoperative gabapentin
      600 mg in the setting of multimodal analgesia reduces postcesarean delivery pain
      and increases maternal satisfaction in comparison with placebo.

PMID- 21081765
TI  - The possible influence of pulmonary arterio-venous shunt and hypoxic pulmonary
      vasoconstriction on arterial sevoflurane concentration during one-lung
      ventilation.
AB  - Sevoflurane is widely used for its rapid onset and offset due to a lower
      blood/gas coefficient. However, involuntary movements, tachycardia, and
      hypertension have been observed in some patients despite a continuing constantly
      delivered concentration of sevoflurane during 1-lung ventilation (OLV),
      indicating the possibility of insufficient depth of anesthesia. We observed a
      temporary but obvious decrease in arterial sevoflurane concentration and pulse
      oximeter readings in a patient during OLV. This may have resulted in the depth of
      inhaled anesthesia being insufficient during OLV because the arterial sevoflurane
      concentration was lower than expected in spite of constantly delivered and
      inspiratory/expiratory sevoflurane concentrations.

PMID- 21081766
TI  - Self-reported information needs of anesthesia residency applicants and analysis
      of applicant-related web sites resources at 131 United States training programs.
AB  - BACKGROUND: Despite the use of web-based information resources by both anesthesia
      departments and applicants, little research has been done to assess these
      resources and determine whether they are meeting applicant needs. Evidence is
      needed to guide anesthesia informatics research in developing high-quality
      anesthesia residency program Web sites (ARPWs). METHODS: We used an anonymous web
      based program (SurveyMonkey, Portland, OR) to distribute a survey investigating
      the information needs and perceived usefulness of ARPWs to all 572 Stanford
      anesthesia residency program applicants. A quantitative scoring system was then
      created to assess the quality of ARPWs in meeting the information needs of these
      applicants. Two researchers independently analyzed all 131 ARPWs in the United
      States to determine whether the ARPWs met the needs of applicants based on the
      scoring system. Finally, a qualitative assessment of the overall user experience
      of ARPWs was developed to account for the subjective elements of the Web site's
      presentation. RESULTS: Ninety-eight percent of respondents reported having used
      ARPWs during the application process. Fifty-six percent reported first visiting
      the Stanford ARPW when deciding whether to apply to Stanford's anesthesia
      residency program. Multimedia and Web 2.0 technologies were "very" or "most"
      useful in "learning intangible aspects of a program, like how happy people are"
      (42% multimedia and Web 2.0 versus 14% text and photos). ARPWs, on average,
      contained only 46% of the content items identified as important by applicants.
      The average (SD) quality scores among all ARPWs was 2.06 (0.59) of 4.0 maximum
      points. The mean overall qualitative score for all 131 ARPWs was 4.97 (1.92) of
      10 points. Only 2% of applicants indicated that the majority (75%-100%) of Web
      sites they visited provided a complete experience. CONCLUSION: Anesthesia
      residency applicants rely heavily on ARPWs to research programs, prepare for
      interviews, and formulate a rank list. Anesthesia departments can improve their
      ARPWs by including information such as total hours worked and work hours by
      rotation (missing in 96% and 97% of ARPWs) and providing a valid web address on
      the Fellowship and Residency Electronic Interactive Database Access System
      (FREIDA) (missing in 28% of ARPWs).

PMID- 21081767
TI  - Design, implementation, and evaluation of a computerized system to communicate
      with patients with limited native language proficiency in the perioperative
      period.
AB  - BACKGROUND: Effective communication with patients having limited proficiency in
      the native language of anesthesia care providers during the perioperative period
      is often challenging. We describe how we developed, implemented, and evaluated a
      computerized system to convey frequently used prerecorded phrases related to
      perioperative anesthesia care in the languages we most often encounter in such
      patients. METHODS: Phrases were chosen through a consensus process among
      anesthesia department members. These included routine sayings used to inform
      patients about what they should anticipate, what interventions we are performing,
      and how they can participate. Common questions requiring a "yes" or "no" answer
      were also identified. We recorded these phrases using native speakers who were
      both knowledgeable medically and familiar with the culture of the patients to
      provide accurate translations. We developed a software application that
      categorically grouped the phrases and allowed care providers to select a phrase
      and play the associated sound file to the patient and deployed the program on our
      touchscreen-enabled anesthesia information management system workstations. A
      convenience sample of obstetrical patients speaking a Chinese dialect with whom
      the language program was used were asked to complete an anonymous questionnaire,
      translated into Chinese, about their experience. Ninety-five percent lower
      confidence limits (LCLs) were calculated for response proportions. RESULTS: We
      approached 25 parturients with varying levels of English comprehension, and all
      agreed to use the language program. Each used it throughout her interaction with
      the anesthesia care providers during labor and delivery, and all patients
      completed the survey. Acceptance of the process was high, with all patients
      indicating that they would like to use it again were they to return for another
      procedure requiring anesthesia. Eighty-eight percent (LCL = 73%) indicated that
      having instructions in their native language made them feel more relaxed, whereas
      the experience was neutral in the remainder. Comprehension of the phrases
      presented was high, with 96% (LCL = 83%) indicating that they understood all
      instructions. Ninety-six percent (LCL = 83%) of patients indicated that they
      would be likely to refer friends and family to our institution based on the
      availability of this device. CONCLUSIONS: Although patient safety likely could be
      improved by use of a communication device such as the one we developed, our study
      was insufficiently powered to be able to measure this potential improvement. The
      process we describe should be useful wherever anesthesia care providers are not
      able to communicate in the same language as their patients.

PMID- 21081768
TI  - Preoperative endoscopic airway examination (PEAE) provides superior airway
      information and may reduce the use of unnecessary awake intubation.
AB  - BACKGROUND: Development of a perioperative plan for management of patients with
      airway pathology is a challenge for the anesthesiologist. Lack of comprehensive
      information regarding the architecture of airway lesions often leads the
      clinician to consider techniques of awake intubation (AI) to avoid catastrophic
      outcomes in this population. In one uncontrolled trial, endoscopic visualization
      of the airway lesion was included in the preoperative anesthetic assessment for
      planning of airway management. We sought to determine whether visual inspection
      of airway pathology would change the anesthesiologist's approach to the
      management of these patients. METHODS: Patients presenting for elective
      diagnostic or therapeutic airway procedures were included in the study. After a
      standard examination of the airway, a management plan was recorded. Before
      entering the operating room, and after brief preparation of the nares with a
      vasoconstrictor and local anesthetic, the patients underwent a preoperative
      endoscopic airway examination (PEAE) and a final airway management plan was
      recorded and implemented. Four or more months after the procedure, video
      recordings of the PEAE were reviewed without other patient identifiers and a
      remote PEAE plan was recorded, to test for operator bias. RESULTS: One hundred
      thirty-eight patients were studied. Although AI was initially planned in 44
      patients, only 16 of these patients underwent preinduction airway control after
      PEAE (P > 0.05). Additionally, of the 94 patients for whom the initial plan was
      airway control after the induction of anesthesia, 8 patients were found to have
      unexpectedly severe airway pathology on PEAE, and also underwent AI. There was no
      significant difference between the post-PEAE airway management plan and the
      remote plan recorded 4 or more months later. CONCLUSIONS: In 26% of the patients
      studied, PEAE affected the planned airway management. We believe that PEAE can be
      an essential component of the preoperative assessment of patients with airway
      pathology; airway visualization reduces the number of unnecessary AIs while
      providing superior information about the airway architecture. PEAE could be
      applied to other populations of patients at risk for airway control failure with
      the induction of anesthesia.

PMID- 21081769
TI  - Accurate classification of difficult intubation by computerized facial analysis.
AB  - BACKGROUND: Bedside airway evaluation is conduced before anesthesia, but all
      current methods perform modestly, with low sensitivity and positive predictive
      value. We hypothesized that subjective features of patients' anatomies improve
      anesthesiologists' ability to predict difficult intubation, and derived a
      computer model to do so, based on analysis of photographs of patients' faces.
      METHODS: Eighty male patients were divided into 2 equal cohorts for model
      derivation and validation. Each cohort consisted of 20 easy and 20 challenging
      intubations, defined as >1 attempt by an operator with at least 12 months of
      anesthesia experience, grade 3 or 4 laryngoscopic view, need for a second
      operator, or nonelective use of an alternative airway device. Photographs of each
      subject's face were analyzed by software that resolves each face into 61 facial
      proportions derived from an algorithm that models the face as a single point in a
      50-dimensional eigenspace. Each parameter was tested for discriminatory ability
      by logistic regression, and combinations of 11 variables with P <= 0.1, plus
      Mallampati class and thyromental distance, were tested exhaustively by all
      possible binomial quadratic logistic regression models. Candidate models were
      cross-validated by maximizing the product of the area under the receiver
      operating characteristic curves obtained in the derivation and validation
      cohorts. RESULTS: The best model included 3 facial parameters and thyromental
      distance. It correctly classified 70 of 80 subjects (P < 10(-8)). In contrast,
      the best combination of Mallampati class and thyromental distance correctly
      classified 47 of 80 (P = 0.073). Sensitivity, specificity, and area under the
      curve for the computer model were 90%, 85%, and 0.899, respectively. CONCLUSIONS:
      Computerized analysis of facial structure and thyromental distance can classify
      easy versus difficult intubation with accuracy significantly outperforming
      popular clinical predictive tests.

PMID- 21081770
TI  - Case report: bilateral angle closure glaucoma after general anesthesia.
AB  - Acute angle closure glaucoma is a rare complication of general anesthesia.
      However, in case of delayed diagnosis, it may lead to blindness. We present a
      case of bilateral acute angle closure glaucoma after cervical spine surgery under
      general anesthesia in a hypermetropic patient. In this case, the most likely
      trigger was the use of ephedrine, but nefopam administration and the prone
      surgical position are discussed as additional potential factors.

PMID- 21081762
TI  - Transcriptome response to different carbon sources in Acetobacter aceti.
AB  - The draft genome sequence of Acetobacter aceti NBRC 14818 was determined by whole
      genome shotgun sequencing and the transcriptome profile in cells exponentially
      grown on ethanol, acetate or glucose was analysed by using a DNA microarray. The
      genes for all enzymes that constitute the complete tricarboxylic acid (TCA) cycle
      and glyoxylate pathway were identified in the genome. The TCA cycle genes showed
      higher expression levels in A. aceti cells grown on acetate or glucose and the
      glyoxylate pathway genes were significantly induced by ethanol or acetate. Many
      SOS-response genes were upregulated in cells grown on ethanol, indicating that
      ethanol provoked damage of DNA and proteins. The superoxide dismutase and
      catalase genes showed high expression levels in culture on glucose, indicating
      that oxidation of glucose induced oxidative stress. A. aceti NBRC 14818 was found
      to have a highly branched respiratory chain. The genes for two type I and one
      type II NADH dehydrogenase were identified. The genes for one of the type I
      enzymes were highly expressed when cells were grown on acetate or glucose, but
      were significantly downregulated in culture on ethanol, probably because
      ubiquinones were directly reduced by pyrroloquinoline quinone-dependent alcohol
      dehydrogenase. Four sets of the genes for quinol oxidases, one bo(3)-type (BO3),
      one bd-type and two cyanide-insensitive-types (CIOs), were identified in the
      genome. The genes for BO3, which might have proton-pumping activity, were highly
      expressed under the conditions tested, but were downregulated in the glucose
      culture. In contrast, the genes for one of the CIOs were significantly
      upregulated in cells grown on glucose. The two CIOs, which are expected to have
      lower energy-coupling efficiency, seemed to have a higher contribution in glucose
      grown cells. These results indicate that energy conservation efficiency is fine
      tuned by changing the respiratory components according to the growth conditions
      in A. aceti cells.

PMID- 21081771
TI  - Survey study of anesthesiologists' and surgeons' ordering of unnecessary
      preoperative laboratory tests.
AB  - BACKGROUND: Nearly 20 years ago it was shown that patients are exposed to
      unnecessary preoperative testing that is both costly and has associated
      morbidity. To determine whether such unnecessary testing persists, we performed
      internal and external surveys to quantify the incidence of unnecessary
      preoperative testing and to identify strategies for reduction. METHODS: The
      medical records of 1000 consecutive patients scheduled for surgery at our
      institution were examined for testing outside of our approved guidelines.
      Subsequently, 4 scenarios were constructed to solicit physician views of
      appropriate testing: a 45-year-old woman for a laparoscopic ovarian cystectomy, a
      23-year-old woman for right inguinal herniorrhaphy, a 50-year-old man for a
      hemithyroidectomy, and a 50-year-old man for a total hip replacement. One or more
      of these scenarios were sent to directors of preoperative clinics (all), United
      States anesthesiologists (all), gynecologists (cystectomy), general surgeons
      (herniorrhaphy), otolaryngologists (thyroidectomy), and orthopedists (hip
      replacement). Potential predictors of ordering and demographic information were
      collected. RESULTS: More than half of our patients had at least 1 unnecessary
      test based on our testing guidelines (95% lower confidence limit = 52%). The 17
      responding preoperative directors were unanimous for 36 of the 72 combinations of
      test or consult (henceforth "test") and scenario as being unnecessary. Among the
      175 anesthesiologists responding to the survey, 46% ordered 1 or more of the
      tests unanimously considered unnecessary by the preoperative directors for the
      given scenario. Among 17 potential predictors of anesthesiologists' unnecessary
      ordering, only training completed before 1980 significantly increased the risk of
      ordering at least 1 unnecessary test (by 48%, 95% confidence limits >29%).
      Anesthesiologists were 53% less likely to order at least 1 unnecessary test
      relative to gynecologists for the cystectomy scenario, 64% less likely than
      general surgeons for the herniorrhaphy scenario, 66% less likely than
      otolaryngologists for the thyroidectomy scenario, and 67% less likely than
      orthopedists for the hip replacement scenario. The 95% lower confidence limits
      were all >40%. CONCLUSIONS: The percentage of patients with at least 1
      unnecessary test is a suitable end point for monitoring providers' ordering. The
      incidence can be high despite efforts at improvement, but may be reduced if
      anesthesiologists rather than surgeons order presurgical tests and consults.
      However, anesthesia groups should be cognizant of potential heterogeneity among
      them based on time since training.

PMID- 21081773
TI  - The anticonvulsant effects of propofol and a propofol analog, 2,6-diisopropyl-4
      (1-hydroxy-2,2,2-trifluoroethyl)phenol, in a 6 Hz partial seizure model.
AB  - BACKGROUND: Propofol is a general anesthetic having good anticonvulsant
      properties, but is limited in antiseizure use because of its potent
      anesthetic/sedative properties. It is proposed that substitution of the propofol
      molecule in the para position may yield compounds having less toxicity, yet
      possessing anticonvulsant properties because of retention of the 2,6
      diisopropylphenol configuration. Reported herein is the synthesis of a para
      substituted analog of propofol, 2,6-diisopropyl-4-(1-hydroxy-2,2,2
      trifluoroethyl)phenol (MB003), and a similar analog of 2,6-di-sec-butylphenol
      (MB050), and their comparative anticonvulsant effects in National Institute of
      Neurological Disorders and Stroke screening models. METHODS: MB003 and MB050 were
      synthesized by the reaction of propofol or 2,6-di-sec-butylphenol, respectively,
      with trifluoroacetaldehyde ethyl hemiacetal in the presence of catalytic amounts
      of K(2)CO(3). Compounds were purified to >98% purity. Propofol, MB003, 2,6-di-sec
      butylphenol, and MB050 were screened for protective effects by the National
      Institute of Neurological Disorders and Stroke Anticonvulsant Screening Program
      in the mouse maximal electroshock, subcutaneous metrazol, and 6 Hz (32 mA)
      partial seizure models. All compounds were administered by i.p. injection. The
      toxicity of each compound was assessed by the ability of the animals to stay on a
      Rotorod after dosing. RESULTS: Propofol, MB003, and MB050 were found to be most
      protective in the 6 Hz model with lesser protective effects in the mouse maximal
      electroshock and subcutaneous metrazol models. In the 6 Hz model, propofol
      yielded a 50% effective dose of 32.8 mg/kg; MB003, 38.4 mg/kg; and MB050, 74.0
      mg/kg. Propofol, and to a greater degree, 2,6-di-sec-butylphenol, exhibited high
      toxicity. The corresponding 2,6-dimethylphenol analog to MB003 and MB050, 2,6
      dimethyl-4-(1-hydroxy-2,2,2-trifluoroethyl)phenol, was not protective in the 6 Hz
      model and exhibited no toxicity at any dose tested. CONCLUSION: These results
      show that the anesthetics propofol and 2,6-di-sec-butylphenol may be substituted
      in the para position with a 1-hydroxy-2,2,2-trifluoroethyl moiety and the
      resulting molecules have anticonvulsant activity in the 6 Hz model while
      exhibiting less toxicity (ataxia) than the parent 2,6-dialkylphenols. The
      effectiveness of propofol, MB003, 2,6-di-sec-butylphenol, and MB050 and the
      ineffectiveness of 2,6-dimethyl-4-(1-hydroxy-2,2,2-trifluoroethyl)phenol, in the
      6 Hz model shows that the 2,6-diisopropyl or 2,6-di-sec-butyl phenolic
      configuration is more important to anticonvulsant activity than having the
      phenolic para position free of substituents. These results suggest that 1-hydroxy
      2,2,2-trifluoroethyl substituted 2,6-di-alkylphenols may have useful
      anticonvulsant activities.

PMID- 21081772
TI  - Acupuncture in critically ill patients improves delayed gastric emptying: a
      randomized controlled trial.
AB  - BACKGROUND: Malnutrition remains a severe problem in the recovery of critically
      ill patients and leads to increased in-hospital morbidity and in-hospital stay.
      Even though early enteral nutrition has been shown to improve overall patient
      outcomes in the intensive care unit (ICU), tubefeed administration is often
      complicated by delayed gastric emptying and gastroesophageal reflux. Acupuncture
      has been successfully used in the treatment and prevention of perioperative
      nausea and vomiting. In this study we evaluated whether acupuncture can improve
      gastric emptying in comparison with standard promotility drugs in critically ill
      patients receiving enteral feeding. METHODS: Thirty mechanically ventilated
      neurosurgical ICU patients with delayed gastric emptying, defined as a gastric
      residual volume (GRV) >500 mL for >= 2 days, were prospectively and randomly
      assigned to either the acupoint stimulation group (ASG; bilateral transcutaneous
      electrical acupoint stimulation at Neiguan, PC-6) or the conventional promotility
      drug treatment group (DTG) over a period of 6 days (metoclopramide, cisapride,
      erythromycin). Patients in the ASG group did not receive any conventional
      promotility drugs. Successful treatment (feeding tolerance) was defined as GRV
      <200 mL per 24 hours. RESULTS: Demographic and hemodynamic data were similar in
      both groups. After 5 days of treatment, 80% of patients in the ASG group
      successfully developed feeding tolerance versus 60% in the DTG group. On
      treatment day 1, GRV decreased from 970 +/- 87 mL to 346 +/- 71 mL with acupoint
      stimulation (P = 0.003), whereas patients in the DTG group showed a significant
      increase in GRV from 903 +/- 60 mL to 1040 +/- 211 mL (P = 0.015). In addition,
      GRV decreased and feeding balance (defined as enteral feeding volume minus GRV)
      increased in more patients in the ASG group (14 of 15) than in the DTG group (7
      of 15; P = 0.014). On treatment day 1, the mean feeding balance was significantly
      higher in the ASG group (121 +/- 128 mL) than in the DTG group (-727 +/- 259 mL)
      (P = 0.005). Overall, the feeding balance improved significantly on all days of
      treatment in comparison with the DTG group. Patients in the DTG group did not
      show an increase in feeding balance until day 6. CONCLUSIONS: We introduce a new
      protocol for acupuncture administration in the critical care setting. We
      demonstrated that this protocol was more effective than standard promotility
      medication in the treatment of delayed gastric emptying in critically ill
      patients. Acupoint stimulation at Neiguan (PC-6) may be a convenient and
      inexpensive option (with few side effects) for the prevention and treatment of
      malnutrition in critically ill patients.

PMID- 21081774
TI  - Case report: computed tomography scan-guided Gasserian ganglion injection of
      dexamethasone and lidocaine for the treatment of recalcitrant pain associated
      with herpes simplex type 1 infection of the ophthalmic division of the trigeminal
      nerve.
AB  - We describe the case of a 17-year-old boy with dermatologic herpes simplex virus
      1 outbreaks with incapacitating facial pain requiring multiple hospitalizations.
      He failed to respond to aggressive treatments including antiviral drugs, opioid
      analgesics, stellate ganglion, and supraorbital and supratrochlear nerve blocks.
      The patient elected to undergo dexamethasone and lidocaine Gasserian ganglion
      block under computed tomography-scan guidance. He had immediate and complete
      relief of his pain for the first time in almost 2 years. The patient remained
      pain free during 6-month follow-up visits. This is the first reported use of
      Gasserian ganglion block for treatment of herpes simplex virus-1 infection of the
      trigeminal nerve.

PMID- 21081775
TI  - Perioperative pulmonary outcomes in patients with sleep apnea after noncardiac
      surgery.
AB  - BACKGROUND: Although patients with sleep apnea (SA) are considered to be at
      increased risk for postoperative complications, evidence supporting increased
      risk of perioperative pulmonary morbidity is limited. The objective of this
      study, therefore, was to analyze perioperative demographics and pulmonary
      outcomes of patients with SA after orthopedic and general surgical procedures
      using a population-based sample. We hypothesized that SA is an independent risk
      factor for perioperative pulmonary complications, thus providing a basis for an
      increase in the utilization of resources, including intensive monitoring and
      development of strategies to prevent and treat these events. METHODS: National
      Inpatient Sample data for each year between 1998 and 2007 were accessed.
      Orthopedic and general surgical procedures were included and discharges with a
      diagnosis code for SA were identified. Patients with the diagnosis of SA were
      matched to those without the disease based on demographic variables using the
      propensity scoring method. Aspiration pneumonia, adult respiratory distress
      syndrome (ARDS), pulmonary embolism (PE), and the need for intubation and
      mechanical ventilation were the primary outcomes. Odds ratio (OR) and absolute
      risk reduction along with 95% confidence interval were reported. RESULTS: We
      identified 2,610,441 entries for orthopedic and 3,441,262 for general surgical
      procedures performed between 1998 and 2007. Of those, 2.52% and 1.40%,
      respectively, carried a diagnosis of SA. Patients with SA developed pulmonary
      complications more frequently than their matched controls after both orthopedic
      and general surgical procedures, respectively (i.e., aspiration pneumonia: 1.18%
      vs 0.84% and 2.79% vs 2.05%; ARDS: 1.06% vs 0.45% and 3.79% vs 2.44%;
      intubation/mechanical ventilation: 3.99% vs 0.79% and 10.8% vs 5.94%, all P
      values <0.0001). Comparatively, PE was more frequent in SA patients after
      orthopedic procedures (0.51% vs 0.42%, P = 0.0038) but not after general surgical
      procedures (0.45% vs 0.49%, P = 0.22). SA was associated with a significantly
      higher adjusted OR of developing pulmonary complications after both orthopedic
      and general surgical procedures, respectively, with the exception of PE (OR for
      aspiration pneumonia: 1.41 [1.35, 1.47] and 1.37 [1.33, 1.41]; for ARDS: 2.39
      [2.28, 2.51] and 1.58 [1.54, 1.62]; for PE: OR 1.22 [1.15, 1.29] and 0.90 [0.84,
      0.97]; for intubation/mechanical ventilation: 5.20 [5.05, 5.37] and 1.95 [1.91,
      1.98]). CONCLUSION: SA is an independent risk factor for perioperative pulmonary
      complications. Our results may be used for hypothesis generation for clinical
      studies targeted to improve perioperative outcomes in this patient population.

PMID- 21081776
TI  - A comparison of the combination of aprepitant and dexamethasone versus the
      combination of ondansetron and dexamethasone for the prevention of postoperative
      nausea and vomiting in patients undergoing craniotomy.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) occur commonly after
      craniotomy. In patients receiving prophylaxis with ondansetron and dexamethasone,
      vomiting occurred in 45% of patients at 48 hours. In addition to causing patient
      discomfort, the physical act of vomiting may increase intracranial pressure or
      cerebral intravascular pressure, jeopardizing hemostasis and cerebral perfusion.
      Aprepitant is a neurokin-1 receptor antagonist with a long duration of action and
      no sedative side effect. In a large multicenter study in patients undergoing
      abdominal surgery, aprepitant was significantly more effective than was
      ondansetron in preventing vomiting at 24 and 48 hours postoperatively. We
      hypothesized that the combination of aprepitant with dexamethasone will decrease
      the incidence of postoperative vomiting when compared with the combination of
      ondansetron and dexamethasone in patients undergoing craniotomy under general
      anesthesia. METHODS: Patients scheduled to undergo craniotomy under general
      anesthesia were enrolled in this prospective, double-blind, randomized study.
      Patients were randomized to receive oral aprepitant 40 mg (or matching placebo) 1
      to 3 hours before induction of anesthesia or ondansetron 4 mg IV (or placebo)
      within 30 minutes of the end of surgery. All patients received dexamethasone 10
      mg after induction of anesthesia. The anesthetic technique was standardized. Data
      were collected at regular intervals by blinded personnel for 48 hours after
      surgery. Statistical analysis was performed using Wilcoxon's ranked sum test and
      chi(2) test. P < 0.05 was considered statistically significant. RESULTS: One
      hundred four patients completed the study. The cumulative incidence of vomiting
      at 48 hours was 16% in the aprepitant group and 38% in the ondansetron group (P =
      0.0149). The incidence of vomiting was also decreased in the aprepitant group at
      2 hours (6% vs. 21%, P = 0.0419) and 24 hours (14% vs. 36%, P = 0.0124). From 0
      to 48 hours, there was no difference between the aprepitant and ondansetron
      groups in the incidence of nausea (69% vs. 60%), nausea scores, need for rescue
      antiemetics (65% vs. 60%), complete response (no PONV and no rescue, 22% vs.
      36%), or patient satisfaction with the management of PONV. CONCLUSION: The
      combination of aprepitant and dexamethasone was more effective than was the
      combination of ondansetron and dexamethasone for prophylaxis against
      postoperative vomiting in adult patients undergoing craniotomy under general
      anesthesia. However, there was no difference between the groups in the incidence
      or severity of nausea, need for rescue antiemetics, or in complete response
      between the groups.

PMID- 21081777
TI  - A clinical evaluation of the intubating laryngeal airway as a conduit for
      tracheal intubation in children.
AB  - BACKGROUND: The air-Q Intubating Laryngeal Airway (ILA) (Cookgas LLC, Mercury
      Medical, Clearwater, FL) is a supraglottic airway device available in pediatric
      sizes, with design features to facilitate passage of cuffed tracheal tubes when
      used to guide tracheal intubation. We designed this prospective observational
      study of the ILA to assess the ease of its placement in paralyzed pediatric
      patients, determine its position and alignment to the larynx using a fiberoptic
      bronchoscope, gauge its efficacy as a conduit for fiberoptic intubation with
      cuffed tracheal tubes, and evaluate the ability to remove the ILA without
      dislodgement of the tracheal tube after successful tracheal intubation. METHODS:
      One hundred healthy children, aged 6 months to 8 years, ASA physical status I to
      II, and scheduled for elective surgery requiring general endotracheal anesthesia
      were enrolled in this prospective study. Based on the manufacturer's guidelines,
      each patient received either a size 1.5 or 2.0 ILA according to their weight. The
      number of attempts for successful insertion, leak pressures, fiberoptic grade of
      view, number of attempts and time for tracheal intubation, time for ILA removal,
      and complications were recorded. RESULTS: ILA placement, fiberoptic tracheal
      intubation, and ILA removal were successful in all patients. The size 1.5 ILA
      cohort had significantly higher rates of epiglottic downfolding compared with the
      size 2.0 ILA cohort (P < 0.001), despite adequate ventilation variables. When
      comparing fiberoptic grade of view to weight, a moderate negative correlation was
      found (r = -0.41, P < 0.001), indicating that larger patients tended to have
      better fiberoptic grades of view. The size 1.5 ILA cohort had a significantly
      longer time to intubation (P = 0.04) compared with the size 2.0 ILA cohort.
      However, this difference may not be clinically significant because there was a
      large overlap of confidence bounds in the average times of the size 1.5 ILA (27.0
      +/- 13.0 seconds) and size 2.0 ILA cohorts (22.7 +/- 6.9 seconds). When comparing
      weight to time to tracheal intubation, a weak correlation that was not
      statistically significant was found (r = -0.17, P = 0.09), showing that time to
      intubation did not differ significantly according to weight, despite higher
      fiberoptic grades in smaller patients. CONCLUSIONS: The ILA was easy to place and
      provided an effective conduit for tracheal intubation with cuffed tracheal tubes
      in children with normal airways. Additionally, removal of the ILA after
      successful intubation could be achieved quickly and without dislodgement of the
      tracheal tube. Because of the higher incidence of epiglottic downfolding in
      smaller patients, the use of fiberoptic bronchoscopy is recommended to assist
      with tracheal intubation through this device.

PMID- 21081779
TI  - Etiology and assessment of hypercoagulability with lessons from heparin-induced
      thrombocytopenia.
AB  - Hypercoagulability, or thrombophilia, is a condition associated with an
      abnormally increased tendency toward blood clotting. Affected individuals are
      prone to developing venous or arterial thrombosis and often require
      thromboprophylaxis. Hypercoagulability can be generally classified as either an
      inherited or acquired condition. Patients with an inherited thrombophilia have
      genetic variances that alter the quality or quantity of proteins involved with
      hemostasis. Hypercoagulability may also be acquired and develop as an
      exaggeration of normal physiologic responses to major tissue injury, or an
      abnormal response to various prothrombotic clinical factors. Careful assessment
      for hypercoagulability is important because effective management strategies,
      often involving anticoagulation, may be available. Heparin-induced
      thrombocytopenia is an example of an acquired hypercoagulable state that has been
      well studied and, when recognized, responds to appropriate therapy. In this
      article, we review the etiology, risks, and assessment of thrombophilia, with
      emphasis on the clinical lessons learned from heparin-induced thrombocytopenia.

PMID- 21081778
TI  - Etanercept restores the antinociceptive effect of morphine and suppresses spinal
      neuroinflammation in morphine-tolerant rats.
AB  - BACKGROUND: In the present study we examined the effect of the tumor necrosis
      factor (TNF)-alpha antagonist etanercept on the antinociceptive effect of
      morphine in morphine-tolerant rats. METHODS: Male Wistar rats were implanted with
      2 intrathecal catheters, and 1 was connected to a mini-osmotic pump for either
      morphine (15 MUg/h) or saline (1 MUL/h) infusion for 5 days. On day 5, either
      etanercept (5 MUg, 25 MUg, and 50 MUg/10 MUL) or saline (10 MUL) was injected via
      the other catheter after morphine infusion was discontinued. Three hours later,
      morphine (15 MUg/10 MUL, intrathecally) was given and tail-flick latency was
      measured to evaluate the antinociceptive effect of morphine. Rats were then
      killed and their spinal cords were removed for quantitative real-time polymerase
      chain reaction and immunohistochemistry to measure proinflammatory cytokines
      expression. RESULTS: We found that acute etanercept (50 MUg) treatment preserved
      a significant antinociceptive effect of morphine in morphine-tolerant rats. In
      addition, the expression of TNFalpha mRNA was increased by 2.5-fold, interleukin
      (IL)-1beta mRNA increased by 13-fold and IL-6 mRNA by 111-fold in the dorsal
      spinal cord of morphine-tolerant rats. The increase in TNFalpha, IL-1beta, and IL
      6 mRNA expression was blocked by 50 MUg etanercept pretreatment. The
      immunohistochemistry analysis revealed that 50 MUg etanercept suppressed
      proinflammatory cytokines expression and neuroinflammation in the microglia.
      CONCLUSIONS: The present study demonstrates that etanercept restores the
      antinociceptive effect of morphine in morphine-tolerant rats by inhibition of
      proinflammatory cytokine TNF-alpha, IL-1beta, and IL-6 expression and spinal
      neuroinflammation. The results suggest that etanercept could also be an adjuvant
      therapy for morphine tolerance, which extends the effectiveness of opioids in
      clinical pain management.

PMID- 21081780
TI  - Intrathecal administration of botulinum neurotoxin type A attenuates formalin
      induced nociceptive responses in mice.
AB  - BACKGROUND: Botulinum neurotoxin type A (BoNT/A) has been used as an analgesic
      for myofascial pain syndromes, migraine, and other types of headaches. Although
      an antinociceptive effect of central or peripheral administration of BoNT/A is
      suggested, the effect at the spinal level is still unclear. In this study, we
      evaluated the antinociceptive effect of intrathecally administered BoNT/A on the
      ICR mice during the formalin test. METHODS: BoNT/A (0.01 U/mouse) was injected
      intrathecally in ICR mice, and we observed formalin-induced inflammatory pain
      behaviors at days 1, 4, 7, 10, 14, 21, and 28 after the injection. We also
      examined the level of calcitonin gene-related peptide (CGRP), phosphorylated
      extracellullar signal-regulated kinases (p-ERK), and phosphorylated
      Ca(2+)/calmodulin-dependent protein kinase type 2 (p-CaMK-II) using immunoblot or
      immunohistochemical analyses before and after BoNT/A intrathecal injection.
      RESULTS: Even a single intrathecal injection of BoNT/A significantly decreased
      the nociceptive responses in the first phase (10 and 14 days later) and in the
      second phase of the formalin test at 1, 4, 7, 10, and 14 days later (P < 0.05)
      without any locomotor changes. Interestingly, intrathecal BoNT/A attenuated the
      expression level of CGRP, p-ERK, and p-CaMK-II in the 4th and 5th lumbar spinal
      dorsal horn at 10 days after injection in comparison with control. CONCLUSIONS:
      We showed that intrathecally administered BoNT/A may have a central analgesic
      effect on inflammatory pain through the modulation of central sensitization.
      BoNT/A, with its long-lasting antinociceptive effect, may be a useful analgesic
      in inflammatory pain.

PMID- 21081782
TI  - Improving patients' understanding of cancer.

PMID- 21081783
TI  - Thyroid carcinoma.

PMID- 21081784
TI  - Complications of radioactive iodine treatment of thyroid carcinoma.
AB  - Radioactive iodine (RAI) in the form of (131)I has been used to treat thyroid
      cancer since 1946. RAI is used after thyroidectomy to ablate the residual normal
      thyroid remnant, as adjuvant therapy, and to treat thyroid cancer metastases.
      Although the benefits of using RAI in low-risk patients with thyroid cancer are
      debated, it is frequently used in most patients with thyroid cancer and is
      clearly associated with acute and long-term risks and side effects. Acute risks
      associated with RAI therapy include nausea and vomiting, ageusia (loss of taste),
      salivary gland swelling, and pain. Longer-term complications include recurrent
      sialoadenitis associated with xerostomia, mouth pain, dental caries, pulmonary
      fibrosis, nasolacrimal outflow obstruction, and second primary malignancies. This
      article summarizes the common complications of RAI and methods to prevent and
      manage these complications.

PMID- 21081785
TI  - Initial management and follow-up of differentiated thyroid cancer in children.
AB  - Children with differentiated thyroid cancer (DTC) often present with metastatic
      disease and have a high risk for recurrence, but rarely die of the disease. This
      article reviews DTC in children and discusses current approaches to their initial
      care and follow-up. These recommendations take into account the greater risk for
      recurrence and lower disease-specific mortality in these patients. Total
      thyroidectomy and central compartment lymph node dissection are appropriate for
      most children, but should be performed by a high-volume thyroid surgeon.
      Radioactive iodine (RAI) should generally be prescribed for those at very high
      risk for recurrence or known to have microscopic residual disease, and those with
      iodine-avid distant metastases. RAI should be considered in other patients only
      after carefully weighing the relative risks and benefits and the aggressiveness
      of the clinical presentation, because RAI may be associated with an increased
      risk for second malignancies and an increase in overall morbidity and mortality.
      All patients should be treated with thyroid hormone suppression, and follow-up
      should be lifelong. However, the degree of thyroid hormone suppression and
      frequency of disease surveillance usually decrease over time as patients are
      determined to be disease-free.

PMID- 21081786
TI  - Thymic malignancies.

PMID- 21081787
TI  - The biologic spectrum of thymic epithelial neoplasms: current status and future
      prospects.
AB  - Thymoma is the most common anterior mediastinal tumor in adults and is frequently
      associated with autoimmune disorders such as myasthenia gravis. Thymomas are a
      diverse group of epithelial neoplasms with a behavioral spectrum that spans the
      complete clinical gamut from entirely benign to highly aggressive, lethal thymic
      carcinomas. The biologic behavior seems to depend primarily on the clinical stage
      at presentation and histologic subtype. This article discusses thymic
      organogenesis, Masaoka staging, WHO histologic classification of thymoma and
      thymic carcinoma, and selected molecular characteristics that highlight this
      diversity. This discussion will further underscore both the similarities and
      differences between categories of thymic epithelial neoplasms and offer support
      for the notion that tumor heterogeneity and/or tumor progression may explain the
      observed clinical variation in behavior. Recommendations are offered for future
      investigational approaches to further the understanding of the complexity of
      these tumors.

PMID- 21081788
TI  - [Cut to the quick?].

PMID- 21081789
TI  - [Necessity of special legislation for doctors].

PMID- 21081790
TI  - [Survival and causes of death in children diagnosed with cancer in Iceland 1981
      2006].
AB  - OBJECTIVE: Of children diagnosed with cancer, approximately one fourth die of the
      disease or disease related complications. The aim of this study was to
      investigate survival and causes of death in children with cancer in Iceland.
      METHODS: This study is retrospective; population based and includes all children,
      less than 18 years of age, diagnosed with cancer in Iceland from 1981 to 2006.
      Information was extracted from the Icelandic Cancer Registry, patients hospital
      records and data from Statistics Iceland. RESULTS: Of 279 children diagnosed with
      cancer in the research period 215 were alive at the end of 2008. The overall 5
      year survival was 81.2% and 10-year survival was 76.7%. There was not a
      significant survival difference with respect to age at diagnosis, year of
      diagnosis, gender or geographical residence. The small cohort size could be the
      explanation. Eleven individuals developed secondary neoplasm, eight of whom died.
      Sixteen of the 64 nonsurvivors were treated with curative intent until death, 12
      of them died of therapy related complications. CONCLUSIONS: Survival rate in
      childhood cancer in Iceland is comparable to other Western countries. As
      previously reported, prognosis of patients with secondary neoplasm is
      unfavorable. Therapy related complications are the most common cause of death in
      patients treated with curative intent.

PMID- 21081791
TI  - [Burn injuries in children: admissions at Landspitali University Hospital in
      Iceland 2000-2008].
AB  - BACKGROUND: Causes of burn injuries in children are universally associated with
      social and environmental factors. Epidemiological studies are therefore important
      in identifying risk factors and for planning preventive interventions. METHODS:
      Children younger than 18 years with skin burns who were treated as inpatients at
      Landspitali University Hospital over a 9-year period, 2000 and 2008, were
      included in this retrospective descriptive study. Data was collected from medical
      records. RESULTS: Of 149 children included in the study 41.6% were four years old
      or younger. The average annual incidence of hospital admissions was 21/100,000.
      Cold water as first aid was applied in 78% of cases. Half of the accidents
      occurred in the home where a close family member was the caretaker. Risk factors
      were identified in 11.4% of the accidents and abuse or neglect was suspected in
      3.4% of cases. Scalds were the most common type of burn injury (50.3%) followed
      by burns caused by fire (20.4%) including gas or petrol (14.9%) and fireworks
      (17.6%). The most common source of scalds was exposure to hot water from hot
      water mains (12,9%) and heated water (12,9%). The mean time from emergency room
      admission to the paediatric ward was two hours and 22 minutes. The mean length of
      stay was 13 days; median 9 days (range 1-97). CONCLUSION: Incidence of hospital
      admissions for burn injury has decreased when compared with earlier Icelandic
      studies. Children four years and younger and boys between 13-16 years old are
      most at risk for burn injuries. Stronger preventive measures as well as better
      documentation of burn accidents are imperative.

PMID- 21081792
TI  - [The effect of maternal weight on pregnancy outcome].
AB  - OBJECTIVE: To examine the frequency of adverse outcome during pregnancy and
      delivery and neonatal complications among normal weight, overweight and obese
      women at the beginning of pregnancy. MATERIAL AND METHODS: The study is a
      retrospective cohort study of 600 women, divided in 3 groups on the basis of
      maternal body mass index (BMI) at the beginning of pregnancy; 300 normal weight
      women (BMI 19.0-24.9), 150 overweight women (BMI 25.0-29.9) and 150 obese women
      (BMI >= 30). Maternal and neonatal complications were compared between groups.
      RESULTS: Obese women have a significantly increased risk of; essential
      hypertension prior to pregnancy (p<0.001), developing gestational hypertension
      (p=0.03), pre-eclampsia (p=0.007), gestational diabetes (p<0.001),
      musculoskeletal symptoms (p=0.04), requiring induction of labour (pp=0.006) and
      being delivered by cesarean section (p<0.001), both emergent (pp=0.012) and
      elective (pp=0.008) compared to mothers of normal weight and overweight. Neonates
      of obese mothers have significantly higher birth weight (pp=0.004), larger head
      circumference (p<0.001) and are more likely to require admission to neonatal ward
      compared with neonates of normal weight and overweight mothers (pp=0.004).
      CONCLUSIONS: Obesity carries a significant risk to maternal and neonatal health.
      During pregnancy maternal complications are increased causing adverse effects for
      both mother and infant. Women of reproductive age need counselling regarding the
      adverse effects of obesity on pregnancy outcome.

PMID- 21081793
TI  - [Case of the month: headache, amnesia and dysphasia following aortic valve
      replacement. Diagnosis: herpes simplex encephalitis].

PMID- 21081794
TI  - Brain and cardiovascular diseases: common neurogenic background of
      cardiovascular, metabolic and inflammatory diseases.
AB  - In spite of significant progress in pharmacotherapy the incidence of newly
      diagnosed cases of cardiovascular diseases and cardiovascular morbidity is
      alarmingly high. Treatment of hypertension or heart failure still remains a
      serious challenge. Continuous attempts are made to identify the mechanisms that
      decide about susceptibility to pathogenic factors, and to determine effectiveness
      of a specific therapeutic approach. Coincidence of cardiovascular diseases with
      metabolic disorders and obesity has initiated intensive research for their common
      background. In the recent years increasing attention has been drawn to
      disproportionately greater number of depressive disorders and susceptibility to
      stress in patients with coronary artery disease. An opposite relationship, i.e. a
      greater number of sudden cardiovascular complications in patients with
      depression, has been also postulated. Progress in functional neuroanatomy and
      neurochemistry provided new information about the neural network responsible for
      regulation of cardiovascular functions, metabolism and emotionality in health and
      under pathological conditions. In this review we will focus on the role of
      neuromodulators and neurotransmitters engaged in regulation of the cardiovascular
      system, neuroendocrine and metabolic functions in health and in pathogenesis of
      cardiovascular diseases and obesity. Among them are classical neurotransmitters
      (epinephrine and norepinephrine, serotonin, GABA), classical (CRH, vasopressin,
      neuropeptide Y) and newly discovered (orexins, apelin, leptin IL-1beta, TNF
      alpha, ghrelin) neuropeptides, gasotransmitters, eicozanoids, endocannabinoids,
      and some other compounds involved in regulation of neuroendocrine, sympatho
      adrenal and parasympathetic nervous systems. Special attention is drawn to those
      factors which play a role in immunology and inflammatory processes. Interaction
      between various neurotransmitter/neuromodulatory systems which may be involved in
      integration of metabolic and cardiovascular functions is analyzed. The survey
      gives evidence for significant disturbances in release or action of the same
      mediators in hypertension heart failure, obesity, diabetes mellitus, metabolic
      syndrome, starvation, chronic stress, depression and other psychiatric disorders.
      With regard to the pathogenic background of the cardiovascular diseases
      especially valuable are the studies showing inappropriate function of angiotensin
      peptides, vasopressin, CRH, apelin, cytokines and orexins in chronic stress,
      cardiovascular and metabolic diseases. The studies surveyed in this review
      suggest that multiple brain mechanisms interact together sharing the same neural
      circuits responsible for adjustment of function of the cardiovascular system and
      metabolism to current needs.

PMID- 21081795
TI  - Brain-gut axis in the modulation of pancreatic enzyme secretion.
AB  - Pancreatic enzyme secretion is controlled by complex of neurohormonal mechanisms,
      activated by nutrients. Food components in the duodenum acts as the signals for
      activation of intestinal phase of pancreatic secretion. Direct stimulation of
      pancreatic exocrine function involves several hormones, which bind to the
      receptors on pancreatic acinar cell. Indirect mechanism depends on the activation
      of autonomic nervous reflexes. Brain is also implicated in the regulation of
      pancreatic exocrine function. Dorsal vagal complex of the brainstem (DVC) appears
      the center of long vago-vagal cholinergic entero-pancreatic reflex. Mucosal
      terminals, which initiates entro-pancreatic reflex could be stimulated by CCK,
      serotonin and perhaps others peptides, which are released into duodenum from the
      enteroendocrine (EE) cells of the gastrointestinal mucosa. Melatonin, leptin and
      ghrelin are released from the EE cells into the gastrointestinal lumen. These
      substances given intraduodenally to the rats produced dose-dependent stimulation
      of pancreatic enzyme secretion, but they failed to affect directly amylase
      release from isolated pancreatic acini. Intraluminal application of melatonin,
      its precursor: L-tryptophan, leptin or ghrelin dose-dependently increased plasma
      CCK level. Above stimulatory effects of investigated substances on CCK release
      were completely abolished by bilateral, subdiaphragmatic vagotomy, capsaicin
      deactivation of afferent nerves as well as blockade of CCK receptors. We conclude
      that melatonin, leptin or ghrelin, which are released into duodenal lumen by
      nutrients, stimulate pancreatic enzyme secretion by activation of CCK release and
      activation of duodeno-pancreatic reflex.

PMID- 21081796
TI  - The effect of physical activity on the brain derived neurotrophic factor: from
      animal to human studies.
AB  - It is well documented that physical activity can induce a number of various
      stimuli which are able to enhance the strength and endurance performance of
      muscles. Moreover, regular physical activity can preserve or delay the appearance
      of several metabolic disorders in the human body. Physical exercise is also known
      to enhance the mood and cognitive functions of active people, although the
      physiological backgrounds of these effects remain unclear. In recent years, since
      the pioneering study in the past showed that physical activity increases the
      expression of the brain derived neurothophic factor (BDNF) in the rat brain, a
      number of studies were undertaken in order to establish the link between that
      neurothrophin and post-exercise enhancement of mood and cognitive functions in
      humans. It was recently demonstrated that physical exercise can increase plasma
      and/or serum BDNF concentration in humans. It was also reported that physical
      exercise or electrical stimulation can increase the BDNF expression in the
      skeletal muscles. In the present review, we report the current state of research
      concerning the effect of a single bout of exercise and training on the BDNF
      expression in the brain, in both the working muscles as well as on its
      concentrations in the blood. We have concluded that there may be potential
      benefits of the exercise-induced enhancement of the BDNF expression and release
      in the brain as well as in the peripheral tissues, resulting in the improvement
      of the functioning of the body, although this effect, especially in humans,
      requires more research.

PMID- 21081797
TI  - Inhibition of the cardiac L-type calcium channel current by the TRPM8 agonist, (
      )-menthol.
AB  - (-)-Menthol and icilin are agonists of the thermoreceptor non-selective cation
      channel, TRPM8, and are commonly used to investigate TRPM8 function without a
      full appreciation of their non-specific effects. To investigate the hypothesis
      that (-)-menthol and icilin inhibit cardiovascular-type L-type Ca(2+) channel
      currents (I(Ca,L)), the actions of the TRPM8 agonists on rabbit ventricular
      myocyte I(Ca,L) were examined at near-physiological temperature (~35 degrees C)
      using whole-cell recording. Icilin (3-100 MUM) did not significantly inhibit
      I(Ca,L). (3) in contrast, (-)-menthol concentration-dependently inhibited peak
      I(Ca,L) (IC(50)=74.6 MUM; log(10)IC(50)(M)=-4.13+/-0.14). (-)-Menthol blocked the
      late I(Ca,L) remaining at the end of depolarising pulses with greater efficacy
      (96.1+/-2.4% block at 1 mM) than peak I(Ca,L) (68.9+/-5.7% block at 1 mM,
      P<0.01), although there was no difference in potency of block of peak and late
      currents. Block by (-)-menthol showed no voltage-dependence. The actions of (-)
      menthol were compared with those of nimodipine. Nimodipine was a more efficacious
      (97.3+/-1.5 % block at 30 MUM, P<0.01) and potent (IC(50)=0.74 MUM;
      log(10)IC(50)(M)=-6.13+/-0.08, P<0.0001) blocker of peak I(Ca,L) than (-)
      menthol. In contrast to (-)-menthol, nimodipine showed greater potency
      (IC(50)=0.056 MUM; log(10)IC(50)(M)=-7.25+/-0.17, P<0.0001), but not greater
      efficacy, in block of late compared with peak I(Ca,L). In summary, these data
      demonstrate that, at near-physiological temperature, (-) -menthol blocks cardiac
      I(Ca,L) at concentrations similar to those reportedly effective in TRPM8-agonism.
      The data suggest that the mechanism of L-type Ca(2+) channel block by (-)-menthol
      differs from that of nimodipine.

PMID- 21081798
TI  - Neurogenic and myogenic resting skin blood flowmotion in subjects with masked
      hypertension.
AB  - The aim of our study was to investigate, whether masked hypertension (MH) and
      sustained hypertension (HT) are associated with alteration of resting skin blood
      flow and flowmotion. Subjects recruited to the study were assigned to three
      groups according to the results of blood pressure (BP) measurements. Resting
      blood flow (RF) and an index of cutaneous vascular conductance (CVC), were
      measured by Laser Doppler Flowmetry (LDF). Total power of the studied interval
      and five subintervals related to: endothelium, sympathetic, myogenic, respiration
      and heart activity, were analyzed. Serum glucose, sodium level, lipid profile, as
      well as insulin, endothelin and norepinephrine levels were measured. The study
      population consisted of 82 persons: 29 NT, 17 MH and 36 HT. There were no
      differences between the study groups with respect to age and gender, but they
      significantly differed with respect to body mass index (p=0.04) and waist
      circumference (p=0.02), triglyceride levels (p=0.04; highest in HT group),
      norepinephrine levels (p=0.01; highest in MH group). RF as well as CVC RF were
      similar in NT, MH and HT groups. Power spectrum of sympathetic origin was
      significantly different in the study groups (p=0.03), with highest values in MH
      group. Moreover, the subjects with MH revealed increased power spectrum of
      myogenic activity, both absolute (p=0.05) and relative (p=0.08). Daytime systolic
      BP was the most consistent predictor of sympathetic and myogenic origin of
      elevated skin blood flowmotion in multiple regression models. Our findings
      suggest that subjects with MH revealed altered microcirculation with elevated
      resting flowmotion of sympathetic and myogenic origin.

PMID- 21081799
TI  - Ibuprofen administration during endurance training cancels running-distance
      dependent adaptations of skeletal muscle in mice.
AB  - Exercise training induces many adaptations in skeletal muscle, representative
      examples of which include an increase in the IIa myofibre and an increase in the
      capillary-to-fibre ratio (C:F ratio). Moreover, these phenomena are thought to be
      dependent on running distance. Ibuprofen is one non-steroidal anti-inflammatory
      drug that is often used as an analgesic, but its effect on skeletal muscle
      adaptation during endurance training is unclear. In the present study, therefore,
      we administered ibuprofen to mice during running wheel exercise for four weeks,
      and examined its effects on the increase in the IIa myofibre and the C:F ratio in
      skeletal muscle. We observed a significant increase of the IIa myofibre and C:F
      ratio even in the presence of ibuprofen. Moreover, in untreated mice, there was a
      significant positive and strong correlation between these parameters and running
      distance. These results indicate that the increase in the IIa myofibre and the
      C:F ratio in skeletal muscle usually depend on running distance. Interestingly,
      we observed no significant correlation between these parameters and running
      distance in ibuprofen-administered mice. Moreover, we found no significant
      increase of these parameters when the running distance was significantly
      increased, in comparison with untreated mice. These results indicate that
      ibuprofen administration during endurance training cancels running-distance
      dependent adaptations in skeletal muscle. This suggests that even if ibuprofen
      administration facilitates longer-distance running, no further effects of
      training on skeletal muscle can be expected.

PMID- 21081800
TI  - Missorting of cathepsin B into the secretory compartment of CI-MPR/IGFII
      deficient mice does not induce spontaneous trypsinogen activation but leads to
      enhanced trypsin activity during experimental pancreatitis--without affecting
      disease severity.
AB  - The lysosomal protease cathepsin B is thought to play a crucial role in the
      intracellular activation cascade of digestive proteases and in the initiation of
      acute pancreatitis. Although cathepsin B has been shown to be physiologically
      present in the secretory pathway of pancreatic acinar cells it has been suggested
      that premature activation of zymogens requires an additional redistribution of
      cathepsin B into the secretory compartment. Here, we studied the role of
      cathepsin B targeting during caerulein-induced pancreatitis in mouse mutants
      lacking the cation-independent mannose 6-phosphate/insulin-like growth factor II
      receptor (CI-MPR) which normally mediates the trafficking of cathepsin B to
      lysosomes. Absence of the CI-MPR led to redistribution of cathepsin B to the
      zymogen granule enriched subcellular fraction and to a substantial formation of
      large cytoplasmic vacuoles that contained both, trypsinogen and cathepsin B.
      However, this did not cause premature intracellular trypsin activation in saline
      treated control animals lacking the CI-MPR. During caerulein-induced
      pancreatitis, trypsinogen activation in the pancreas of CI-MPR-deficient animals
      was about 40% higher than in wild-type animals but serum amylase levels were
      reduced and lung damage was unchanged. These data suggest that subcellular
      redistribution of cathepsin B, in itself, induces neither spontaneous trypsinogen
      activation nor pancreatitis. Furthermore, we clearly show that a marked increase
      in intracellular trypsinogen activation is not necessarily associated with
      greater disease severity.

PMID- 21081801
TI  - The effects of L-tryptophan and melatonin on selected biochemical parameters in
      patients with steatohepatitis.
AB  - Nonalcoholic fatty liver disease is the most common chronic liver disease and
      nonalcocholic steatohepatitis (NASH) is its advanced form. Oxidative stress and
      hepatocyte apoptosis may be involved in pathogenesis of NASH and particularly in
      progress of NASH to liver fibrosis and cirrhosis, which are initiated by the
      inflammation and which promote the progress of the disease. The aim of this study
      was to evaluate the effects of melatonin and L-tryptophan on selected biochemical
      parameters of blood in patients with NASH. Forty five patients with NASH,
      confirmed by histopathological examination of liver biopsy samples, were admitted
      to the study. They were divided into three groups (I, II and III). The first
      group (group I, n=15) received preparation Essentiale forte 3 times a day and
      tryptophan 500 mg twice daily for 4 weeks. In the second group (group II, n=15),
      Essentiale forte three times a day was administered with melatonin 5 mg applied
      twice a day for 4 weeks. The third group (group III, n=15) received only
      Essentiale forte with placebo three times a day for 4 weeks. After four-week
      treatment we found statistically significant reduction in GGTP, triglycerides and
      proinflammatory cytokine levels in the melatonin-treated (group I) and the L
      tryptophan-treated patients (group II). Plasma level of melatonin was
      significantly elevated in groups treated with tryptophan (group I) and melatonin
      (group II), but remained unchanged in placebo-treated group (group III). Among
      patients from the third group (treated with placebo) no statistically significant
      differences in the measured biochemical parameters were observed. The present
      study suggests that melatonin and tryptophan have the significant impact on the
      reduction in plasma levels of proinflammatory cytokines and may be useful in the
      treatment of patients with NASH.

PMID- 21081802
TI  - Importance of luminal and mucosal zinc in the mechanism of experimental gastric
      ulcer healing.
AB  - Zinc has been reported to exert a gastroprotective action against various
      experimental gastric lesions suggesting that this trace element is involved in
      the integrity of the gastric mucosa. Compounds containing zinc, such as
      polaprezinc, were developed in Japan and used as an antiulcer drugs in the
      treatment of human peptic ulcer disease. However, the precise mechanism of Zn(2+)
      containing compounds and their effects on mucosal integrity, gastroprotection and
      ulcer healing remain unclear. We have determined the efficacy of zinc
      hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric
      secretion and ulcer healing in rats with chronic gastric ulcers induced by acetic
      acid (initial ulcer area = 28 mm(2)). Rats with gastric ulcers were randomized
      into two groups: A) with gastric fistulas (GF) and B) without gastric fistulas
      and received a daily treatment with zinc hydroaspartate (32-130 mg/kg-d i.g.) for
      3, 7 and 14 days. At the termination of each treatment, the area of gastric
      ulcers were examined by planimetry, the gastric blood flow (GBF) at ulcer margin
      was assessed by laser Doppler flowmetry and H(2)-gas clearance methods. The
      venous blood was withdrawn for a measurement of plasma gastrin levels by
      radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and
      mucosa at the ulcer margin were determined by differential pulse anodic stripping
      voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and
      the gastric biopsy samples were taken for histopathological assessment of the
      quality of ulcer healing. The ulcers healed gradually, with the ulcer area in the
      vehicle control rats being diminished by 15%, 48% and 78% upon ulcer induction at
      3, 7 and 14 days, respectively. Zinc hydroaspartate dose-dependently inhibited
      the area of gastric ulcer, the dose reducing this area by 50% (ID(50)) being
      about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged
      from the baseline immediately after ulcer induction (day 0) and at day 3 but then
      it rose significantly at day 7 after ulcer induction. Treatment with zinc
      hydroaspartate (65 mg/kg-d i.g.), which significantly raised the gastric luminal
      and mucosal levels of Zn(2+), significantly accelerated ulcer healing at day 7
      upon ulcer induction. The GBF, which reached a significantly higher value at the
      ulcer margin than the ulcer bed, was significantly increased in rats treated with
      zinc hydroaspartate compared with vehicle-controls. The gastric acid output was
      significantly inhibited in GF rats with gastric ulcer at day 3 then restored at
      day 14 followed by a significant rise in the plasma gastrin levels. Treatment
      with zinc hydroaspartate significantly inhibited gastric secretion and also
      significantly raised the plasma gastrin level when compared to vehicle-control
      rats. We concluded that 1) trace micronutrients such as Zn(2+) could be
      successfully measured in the gastric juice and gastric mucosa during ulcer
      healing; 2) compounds chelating of Zn(2+) can exert a beneficial influence on the
      ulcer healing via Zn(2+) mediated increase in gastric microcirculation,
      antisecretory activity and gastrin release, which may enhance the cell
      proliferation and differentiation during ulcer healing, ultimately exerting a
      trophic action on the ulcerated gastric mucosa.

PMID- 21081803
TI  - Effect of quercetin on kinetic properties of renal Na,K-ATPase in normotensive
      and hypertensive rats.
AB  - The effect of quercetin, a plant-derived bioflavonoid with documented positive
      effect on the cardiovascular system, was examined after 4-week supplementation in
      the dose of 20 mg kg(-1) x day(-1) to young male normotensive control (C) and to
      spontaneously hypertensive rats (SHR) over the period of their 5(th)-8(th) week
      of age. The study was focused on the influence of quercetin on properties of the
      renal Na,K-ATPase, a key system in maintaining the homeostasis of sodium in the
      organism. Spontaneous hypertension by itself enhanced the activity of Na,K-ATPase
      probably as a consequence of a higher number of active enzyme molecules, as
      suggested by the 15% increase of V(max), along with improved affinity to ATP, as
      indicated by the 30% decrease in the value of Michaelis-Menten constant K(m) in
      untreated SHR vs. untreated normotensive rats. Quercetin induced a decrease of
      Na,K-ATPase activity in the presence of all ATP and Na(+) concentrations
      investigated. Evaluation of kinetic parameters resulted in a constant V(max)
      value. The ATP-binding properties of the enzyme were not influenced by quercetin,
      as suggested by statistically insignificant changes in the value of K(m) both in
      controls and in SHR. On the other hand, the affinity to sodium decreased, as
      suggested by an increase in the K(Na) value by 22% and 31% in normotensive and
      hypertensive groups, respectively. This impairment in the affinity of the Na(+)
      binding site of Na,K-ATPase molecules was probably responsible for the
      deteriorated enzyme function in the kidneys of quercetin treated animals.

PMID- 21081804
TI  - Role of hormonal axis, growth hormone - IGF-1, in the therapeutic effect of
      ghrelin in the course of cerulein-induced acute pancreatitis.
AB  - Ghrelin is a ligand for growth hormone secretagogue receptor and stimulates
      release of growth hormone (GH). Recent studies have shown that treatment with
      ghrelin exhibits protective and therapeutic effect in the course of experimental
      pancreatitis. The aim of present study was to examine the role of GH and insulin
      like growth factor-1 (IGF-1) in these effects. Acute pancreatitis was induced by
      cerulein. Study was performed on pituitary-intact hypophysectomized rats. Ghrelin
      was administered twice a day at the dose of 8 nmol/kg/dose. IGF-1 was given twice
      a day at the dose of 20 nmol/kg/dose. The severity of acute pancreatitis was
      assessed 0 h or 1, 2, 3, 5 and 10 days after the last dose of cerulein.
      Administration of cerulein led to the development of acute edematous
      pancreatitis. In pituitary-intact rats, treatment with ghrelin reduced
      biochemical indexes of the severity of acute pancreatitis and morphological signs
      of pancreatic damage, leading to faster regeneration of the pancreas reduction in
      serum concentration of pro-inflammatory interleukin-1beta and decrease in serum
      activity of amylase and lipase. These effects were accompanied with an
      improvement of pancreatic blood flow and an increase in pancreatic DNA synthesis.
      Hypophysectomy delayed the healing of the pancreas and abolished the therapeutic
      effect of ghrelin. In hypophysectomized rats with pancreatitis, treatment with
      IGF-1 exhibits therapeutic effect similar to that observed in ghrelin-treated
      rats with the intact pituitary. We conclude that therapeutic effect of ghrelin in
      cerulein-induced pancreatitis is indirect and depends on the release of GH and
      IGF-1.

PMID- 21081806
TI  - Reactivity of chicken chorioallantoic arteries, avian homologue of human
      fetoplacental arteries.
AB  - The reactivity of human fetoplacental arteries is regulated by humoral and local
      factors of maternal and fetal origin. The chorioallantoic (CA) arteries of bird
      embryos are homologous to fetoplacental arteries and fulfill the same gas
      exchange purpose without maternal influences, but their reactivity has not been
      studied in detail. In the present study we hypothesized that CA arteries would
      respond to vasoactive factors similarly to fetoplacental arteries and the
      response would change during development between maximal vascular CA expansion
      (15 of the 21 days incubation period) and prior to hatching. Therefore, we
      analyzed the reactivity of third order arteries (~200 MUm) from the CA membrane
      of 15 and 19 day chicken embryos. CA arteries contracted in response to K(+), the
      thromboxane A(2) mimetic U46619, endothelin-1, acetylcholine and acute hypoxia,
      but showed no reaction to alpha-adrenergic stimulation (phenylephrine). The
      nitric oxide donor sodium nitroprusside, the adenylyl cyclase agonist forskolin,
      and the beta-adrenergic agonist isoproterenol relaxed CA arteries pre-contracted
      with K(+) or U46619. The contraction evoked by acetylcholine and the relaxations
      evoked by sodium nitroprusside and isoproterenol decreased with incubation age.
      In conclusion, CA arteries share many characteristics with human fetoplacental
      arteries, such as pronounced relaxation to beta-adrenergic stimuli and hypoxic
      vasoconstriction. Our study will be the foundation for future studies to explain
      disparate and common responses of the CA and fetoplacental vasculature.

PMID- 21081805
TI  - The adipose tissue gene expression in mice with different nitric oxide
      availability.
AB  - Mice with the knockout of endothelial nitric oxide synthase (eNOS ko) demonstrate
      symptoms resembling the human metabolic syndrome. NO has been recently
      demonstrated to be deeply involved in regulation of not only blood flow and
      angiogenesis, but also in modulation of mammalian basal energy substrate
      metabolism. Asymmetric dimethylarginine (ADMA) is an endogenous competitive
      inhibitor of NOS. The enzyme dimethylarginine dimethylaminohydrolase (DDAH)
      catabolizes ADMA, what leads to increase of endogenous NO bioavailability. This
      study was aimed to compare the brown (BAT) and white (WAT) adipose tissue gene
      expression of age matched mice with decreased (eNOS ko) and increased
      (overexpressing DDAH) endogenous NO generation. The 19 week old eNOS ko mice
      demonstrated significantly lower weight, higher circulating glucose, insulin,
      leptin and cholesterol concentrations. The adiponectin as well as fasting
      triglyceride concentrations were not significantly altered. Animals with DDAH
      knock in, presented significantly increased angiogenic activity than eNOS ko
      mice. The microarray analysis pointed to activation of adipogenesis-related genes
      in eNOS ko mice in WAT, what was in contrast with the inhibition observed in the
      DDAH overexpressing mice. The angiogenesis related gene expression was down
      regulated in both models in comparison to WT animals. This study support the
      multipotential role of endogenous NO in maintaining homeostasis of energy
      substrate catabolism.

PMID- 21081807
TI  - The effects of adjuvant arthritis on the myometrial adrenergic functions in the
      nonpregnant and the late-pregnant rat.
AB  - The beneficial effects of pregnancy on the symptoms of inflammatory diseases are
      well documented. The modulation in the uterine functions in the presence of
      generalized inflammation, however, is much less characterized. The aim of the
      present study was to explore the modulatory action of adjuvant arthritis on the
      adrenergic functions of the uterus in nonpregnant and late pregnant rats.
      Adjuvant arthritis was induced by the subplantar injection of M. butyricum.
      Presynaptic functions were characterized by a superfusion technique and by
      registration of the contractions of isolated uterine rings elicited by electric
      field stimulation. The functions of the adrenoceptors were characterized by
      constructing concentration-response curves with agonists for both alpha- and beta
      receptors. Where these curves differed significantly from the control, the
      expressions of these receptors at the mRNA level were additionally determined.
      Adjuvant arthritis substantially decreased the uptake and release of
      [(3)H]noradrenaline in myometrial samples from nonpregnant rats, but caused no
      change at term. The electrically induced contractions were decreased by
      inflammation in both gestational states. Arthritis resulted in decreased beta
      adrenoceptor-mediated relaxation (in both the nonpregnant and the late-pregnant
      animals) and an increase in alpha-mediated contraction at term. It can be
      concluded that adjuvant arthritis deteriorates the adrenergic innervation of the
      uterus. The effects of exogenous sympathomimetics are shifted, favoring a state
      of higher contractility. If similar mechanisms are operative in humans, the
      present results could imply that beta-adrenoceptor agonists are not ideal
      tocolytics when pregnancy is complicated by generalized inflammation.

PMID- 21081808
TI  - Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and
      procyanidins potentiates the cytotoxicity of vincristine.
AB  - The purpose of the study was a comparison of Oenothera paradoxa Hudziok defatted
      seeds extract (EPE) effect with the activity of individual constituents of the
      extract: pentagalloylglucose (PGG), gallic acid, (+)-catechin and the procyanidin
      fraction, as well as an assessment of the combined effect of EPE and vincristine
      (VCR) in the absence or presence of MRP1 (indomethacin) and P-glycoprotein
      (verapamil) inhibitors, on two human cancer cell lines, metastatic melanoma (HTB
      140) and hepatoma (HepG2). The presence of EPE, PGG and procyanidins caused a
      marked reduction in viability (MTT assay) and rise in mortality (LDH release
      assay) of HTB-140 cells. The combined use of EPE (25 MUg/mL) and VCR (1 MUM) in
      HTB-140 and HepG2 cells produced an increased cytotoxicity as compared to
      vincristine alone - by more than 4 and 1.5 times, respectively. In HTB-140 cells,
      the level of intracellular ATP (measured by bioluminescence) was lowered over 7
      fold as a result of exposure to the combination of EPE and VCR, while the
      addition of MRP-1 inhibitor did not cause an increased cytotoxicity or further
      lowering of the ATP level. Our results demonstrate that EPE, containing PGG and
      procyanidins, significantly increased the sensitivity of cancer cells,
      particularly the melanoma cells, to the action of vincristine.

PMID- 21081809
TI  - [Long-term outcome of endovascular surgery of intracranial aneurysms].

PMID- 21081810
TI  - [11C-methionine positron emission tomography in nontumorous brain lesions].
AB  - Positron emission tomography (PET) with L-[methyl-11C]methionine (MET) provides
      information on the metabolism of brain tumor. MET uptake reflects amino acid
      active transport and protein synthesis and is proportional to the amount of
      viable tumor cells. However, MET uptake can be increased as a result of increased
      density of inflammatory cells and disruption of the blood brain barrier (BBB) in
      nontumorous brain lesions. From October 2005 through November 2009, 438 MET-PET
      studies were performed for various brain lesions at our institution. Among them,
      27 (6%) were finally diagnosed to be nontumorous by surgical exploration or their
      clinical course. Nine of 10 intracerebral hemorrhages and all 4 cerebral
      infarctions demonstrated mild to moderate MET uptake in or surrounding the
      lesions in the subacute or chronic stage after the ictus. Moderately increased
      MET uptake was observed in all 3 patients with brain abscess. Active lesions in
      multiple sclerosis and Bechet disease showed mild MET uptake. Idiopathic orbital
      and optic inflammations showed mildly increased MET uptake in the lesions.
      Finally, a case of hypertrophic cranial pachymeningitis exhibited strong MET
      uptake in the lesions. We should keep in mind that high MET uptake is frequently
      observed in nontumorous brain lesions. Although differentiation from tumorous
      lesions is usually possible by laboratory and morphological examinations,
      nontumorous lesions should be included in the differential diagnosis when
      encountering patients with high MET uptake.

PMID- 21081811
TI  - [The safety of combination chemotherapy with ifosfamide, cisplatin, and etoposide
      (ICE): single-institution retrospective review of 108 cases].
AB  - PURPOSE: The adverse effects of combination chemotherapy of ifosfamide,
      cisplatin, and etoposide (ICE) were evaluated in the treatment of various
      intracranial brain tumors. METHODS: 108 cases were retrospectively reviewed. The
      histological diagnosis was newly diagnosed or recurrent germ cell tumor in 45
      cases, medulloblastoma in 19, primitive neuroectodermal tumor (PNET) in 7,
      anaplastic ependymoma in 6, recurrent glioblastoma in 13, and others in 18 cases.
      Patients received 1-8 cycles of ICE chemotherapy with or without radiation
      therapy. The adverse effects were analyzed based on the the clinical or
      laboratory examinations. RESULTS: Common Terminology Criteria for Adverse Events
      ver. 3.0 (CTCAE v3.0) grade 4 neutropenia, anemia, and thrombocytopenia occurred
      in 81.4%, 14.8%, and 35.2% of patients, respectively. Non-hematological adverse
      effects, including infection, elevated aspartate aminotransferase (AST)/alanine
      aminotransferase (ALT), high or low levels of serum sodium, and seizure, occurred
      in 26.8%, 29.6%, 28.7%, and 11.1% of patients, respectively. One patient died of
      opportunistic infection with neutropenia. The proportion of ICE cycles associated
      with CTCAE v3.0 grade 4 neutropenia, transfusion of platelets, and elevated
      AST/ALT significantly decreased after enforcement of dose reduction criteria.
      CONCLUSION: The high rate of adverse effects requires close follow up and dose
      reduction.

PMID- 21081812
TI  - [Criteria for applying imaging diagnosis and initial management for pediatric
      head trauma].
AB  - It may be difficult to perform CT for pediatric head trauma because of body
      movement and radiation exposure. Imaging application criteria were established,
      in which patients diagnosed as less likely to have an intracranial lesion meeting
      the criteria were not indicated for imaging and subjected to course observation
      at home, and this policy was explained to the parents. When consent was obtained,
      patients were followed up at home, and we checked on the condition by making a
      phone call 4-8 hours after injury. The patients were 103 infants aged 15 years or
      younger brought to the emergency medical care center of our hospital between May
      and August 2008. Imaging was basically indicated for cases of traffic accidents,
      falls from a high level, those brought in by ambulance, referred cases, and cases
      with disturbance of consciousness, neurologically abnormal findings, vomiting on
      examination, and trauma requiring X-ray examination in addition to that for the
      head. However, apart from these cases, imaging was not required. Imaging was not
      necessary for 94% of infant cases. The parents were convinced by the explanation
      and selected course observation at home in 94% of cases for which imaging was
      judged as unnecessary. None of the patients required re-examination based on the
      conditions reported in phone calls to homes. Imaging diagnosis for pediatric head
      trauma is not always necessary, and its application should be decided on after
      consultation. When no imaging is performed, this should be fully explained at the
      initial treatment before selecting course observation at home. Checking on the
      child's condition by making a phone call several hours after injury is useful for
      both patients and physicians.

PMID- 21081813
TI  - [7 fractionated cyberknife radiotherapy for giant skull metastasis: a case
      report].
AB  - This is a report on the experience of using stereotactic radiotherapy for a large
      symptomatic metastatic skull tumor. The stereotactic radiotherapy was delivered
      in 7 fractions using the Cyberknife and produced excellent therapeutic results.
      This case concerns a 75-year-old female. Nineteen months after uterine cancer
      surgery, the patient demonstrated metastasis to the mediastinum lymph node and a
      tumor at the parietal bone tumor but was still undergoing observation. An
      increase of the parietal bone tumor became evident and the appearance of right
      hemiplegia, aphasia, and cognitive dysfunction caused her to consult this
      hospital. We observed a large 236 cm3 tumor spread over the subcutaneous tissue
      of the superior sagittal sinus, pressing the brain out of the dura mater and
      causing bone destruction. As a result of our findings, we began stereotactic
      Cyberknife radiotherapy delivered in 7 fractions. At the follow up visit one
      month after the treatment, the image of the tumor had already decreased, and
      after three months it was confirmed that the image of the tumor had disappeared.
      The patient's symptoms ameliorated rapidly. As a result, the patient has returned
      to an independent home-lifestyle, with amelioration of her quality-of-life
      defects. Six months after irradiation, there is no evidence of tumor regrowth or
      complications such as dermatopathy, cerebral edema, or necrosis. Cyberknife
      radiotherapy could shorten the treatment period and result in a reduction of the
      amount of irradiation to unaffected parts of the brain. In this case, though the
      tumor had spread widely in the subcutaneous tissue, the exposure doses were
      delivered at 2Gy/time and could be limited to under 70Gy. It is thought that
      Cyberknife radiotherapy will become one of the key treatments to help improve
      quality of life when treating symptomatic metastatic tumors.

PMID- 21081814
TI  - [A case of chondroblastoma arising from the temporal bone].
AB  - A 33-year-old male sustained hearing disturbance in the left ear that exacerbated
      over a period of three years. The patient was referred to the department of
      otorhynolaryngology for severe stenosis of the left external auditory canal,
      where neuroimaging study revealed a huge tumor in the left temporal fossa. On
      first examination, he showed a significant facial nerve paresis and conductive
      hearing loss. CT scans identified a 4.5*4.5*4.5 cm mass with intralesional
      calcification and extensive bony destruction in the squamous and petrous parts of
      the temporal bone and middle cranial fossa floor. MR imaging demonstrated the
      tumor of heterogenous intensity on T1-and hypointensity on T2-weighted image. The
      patient underwent gross total resection of the lesion via frontotemporal
      craniotomy. The bony and ligamentous structures around the temporomandibular
      joint appeared mostly intact and did not need any reconstructive surgery after
      tumor resection. Postoperatively the patient's facial nerve paresis showed a
      transient exacerbation which resolved gradually, while hearing disturbance did
      not improve. Histological findings of the tumor were consistent with the
      qualities of chondroblastoma. We should assume chondroblastoma as differential
      diagnosis when we encounter a temporal bone tumor that is curable by surgical
      resection.

PMID- 21081816
TI  - [Operative neurosurgery: personal view and historical backgrounds (7) reappraisal
      of approaches].
AB  - Selection of an appropriate approach is one of the most important factors for the
      success in neurosurgery, so the following approaches were reappraised in this
      session by giving examples from recent cases. Their standard use has already been
      mentioned elsewhere in the series: 1. Selective extradural anterior clinoidectomy
      SEAC was once more discussed: 1. the origin of en bloc removal has originated, 2.
      meaning of an en bloc replacement, if any, and 3. further development of this
      procedure for low lying upper basilar aneurysms. 2. Trans-sulcus circularis
      insulae approach TSCIA, which is a part of the selective amygdalohippocampectomy
      approach SAHEA was applied for removal of a ganglioglioma originating from the
      head of the hippocampus (cause of intractable temporal lobe epilepsy) of the
      dominant hemisphere without performing SAHE due to a positive selective Wada test
      and the full SAHEA for P2 or P2-3 junction aneurysms (Fig. 1, 2, 3). 3. Trans
      rostrum corporis callosi-lamina terminalis approach TRCLA revealed to be less
      invasive and helpful for removal of a small recurrent craniopharyngioma located
      between the chiasma opticum and the AcomA complex with the use of a small
      craniotomy, avoiding previous craniotomy routes, both pterional and subfrontal,
      for fear of structural adhesion (Fig. 4, 5, 6). 4. Within the scope of the trans
      lobulus quadrangularis approach TLQA, the paramedian supracerebellar
      transtentorial approach SCTTA revealed to be useful for removal of a cavernous
      angioma located at the parahippocampal gyrus corresponding to the head of the
      hippocampus of the dominant hemisphere, so that the possible impairment of
      cognitive function could be avoided, because the incision to the temporal stem
      and to the hippocampus involved in the above mentioned SAHEA could be avoided.
      Furthermore the approach seems to be more rational in the treatment of P2, P2-P3
      junction aneurysms than other approaches especially in the dominant hemisphere
      (Fig. 7, 8, 9). 5. Trans-vertebralis dural ring approach TVDRA revealed to be
      useful in the treatment of microvascular decompression for glossopharyngeal
      neuralgia, because mobilization and displacement of the vertebral artery by
      circumferential incision from its dural ring plays an important role for the
      purpose (Fig. 10, 11). Although the sitting position is necessary for the
      performance of SCTTA and TVDRA, one should know their usefulness and be ready for
      their performance.

PMID- 21081815
TI  - [Sacroiliac joint dysfunction with groin pain after an operation for lumbar
      spinal disorder. A case report].
AB  - A 75-year-old male presented with groin pain after an operation to treat lumbar
      spondylolisthesis (L5). Groin tenderness was localized to the medial border of
      the anterior superior iliac spine (ASIS). Radiographical and physical examination
      raised the suspicion of sacroiliac joint (SIJ) dysfunction. Injection of a
      painkiller into the SIJ relieved symptoms, including groin tenderness. Symptoms
      improved gradually, and finally disappeared after five SIJ injections. Groin pain
      has been reported as a referred symptom of SIJ dysfunction in 9.3-23% of
      patients. Prior to the patient undergoing surgery to treat lumbar
      spondylolisthesis, SIJ dysfunction had not been noted on physical examination.
      Long periods spent in the abnormal posture due to lumbar spondylolisthesis
      induced SIJ stress. After the operation, an improvement in daily activity
      actually increased stress on the SIJ, resulting in SIJ dysfunction. Certain
      pathologies, including SIJ dysfunction, should be considered as residual symptoms
      after operations for lumbar spinal diseases.

PMID- 21081817
TI  - [Understanding clinical neuropsychology: a basic approach (6) brain tumor].

PMID- 21081818
TI  - An x-ray image guidance system for small animal stereotactic irradiation.
AB  - An x-ray image-guided small animal stereotactic irradiator was developed and
      characterized to enable tumor visualization and accurate target localization for
      small field, high dose irradiation. The system utilizes a custom collimation
      system, a motorized positioning system (x, y, theta), a digital imaging panel and
      operating software, and is integrated with a commercial x-ray unit. The essential
      characteristics of the irradiator include small radiation fields (1-10 mm), high
      dose rate (>10 Gy min(-1)) and submillimeter target localization. The software
      enables computer-controlled image acquisition, stage motion and target
      localization providing simple and precise automated target localization. The
      imaging panel was characterized in terms of signal-to-noise ratio (SNR), contrast
      to-noise ratio (CNR) and spatial resolution. Overall localization accuracy and
      precision were assessed. SNR, CNR and spatial resolution are 24 dB, 21 dB and 2.8
      lp mm(-1), respectively, and localization accuracy is approximately 65 um with 6
      um precision. With the aid of image guidance, system performance was subsequently
      used to evaluate radiation response in a rat orthotopic lung tumor effectively
      sparing normal tissues and in a mouse normal lung. The capabilities of 3D
      treatment and cone-beam computed tomography are presented for 3D localization and
      delivery as a work in progress.

PMID- 21081819
TI  - A non-voxel-based broad-beam (NVBB) framework for IMRT treatment planning.
AB  - We present a novel framework that enables very large scale intensity-modulated
      radiation therapy (IMRT) planning in limited computation resources with
      improvements in cost, plan quality and planning throughput. Current IMRT
      optimization uses a voxel-based beamlet superposition (VBS) framework that
      requires pre-calculation and storage of a large amount of beamlet data, resulting
      in large temporal and spatial complexity. We developed a non-voxel-based broad
      beam (NVBB) framework for IMRT capable of direct treatment parameter optimization
      (DTPO). In this framework, both objective function and derivative are evaluated
      based on the continuous viewpoint, abandoning 'voxel' and 'beamlet'
      representations. Thus pre-calculation and storage of beamlets are no longer
      needed. The NVBB framework has linear complexities (O(N(3))) in both space and
      time. The low memory, full computation and data parallelization nature of the
      framework render its efficient implementation on the graphic processing unit
      (GPU). We implemented the NVBB framework and incorporated it with the TomoTherapy
      treatment planning system (TPS). The new TPS runs on a single workstation with
      one GPU card (NVBB-GPU). Extensive verification/validation tests were performed
      in house and via third parties. Benchmarks on dose accuracy, plan quality and
      throughput were compared with the commercial TomoTherapy TPS that is based on the
      VBS framework and uses a computer cluster with 14 nodes (VBS-cluster). For all
      tests, the dose accuracy of these two TPSs is comparable (within 1%). Plan
      qualities were comparable with no clinically significant difference for most
      cases except that superior target uniformity was seen in the NVBB-GPU for some
      cases. However, the planning time using the NVBB-GPU was reduced many folds over
      the VBS-cluster. In conclusion, we developed a novel NVBB framework for IMRT
      optimization. The continuous viewpoint and DTPO nature of the algorithm eliminate
      the need for beamlets and lead to better plan quality. The computation
      parallelization on a GPU instead of a computer cluster significantly reduces
      hardware and service costs. Compared with using the current VBS framework on a
      computer cluster, the planning time is significantly reduced using the NVBB
      framework on a single workstation with a GPU card.

PMID- 21081820
TI  - Optimizing wavelength choice for quantitative optoacoustic imaging using the
      Cramer-Rao lower bound.
AB  - Several papers have recently addressed the issue of estimating chromophore
      concentration in optoacoustic imaging (OAI) using multiple wavelengths. The
      choice of wavelengths obviously affects the accuracy and precision of the
      estimates. One might assume that the wavelengths that maximize the extinction
      coefficients of the chromophores would be the most suitable. However, this may
      not always be the case since the distribution of light intensity in the medium is
      also wavelength dependent. In this paper, we explore a method for optimizing the
      choice of wavelengths based on the Cramer-Rao lower bound (CRLB) on the variance
      of the chromophore concentration. This lower bound on variance can be evaluated
      numerically for different wavelengths using the variation of the extinction
      coefficients and scattering coefficients with wavelength. The wavelengths that
      give the smallest variance will be considered optimal for multi-wavelength OAI to
      estimate the chromophore concentrations. The expression for the CRLB has been
      derived analytically for estimating the concentration of multiple chromophores
      for several simple phantom models for the case when the optoacoustic signal is
      proportional to the product of the optical absorption and the illumination
      function. This approach could be easily extended to other geometries.

PMID- 21081821
TI  - Female workers and in vivo lung monitoring: a simple model for morphological
      dependence of counting efficiency curves.
AB  - This paper addresses the question of the morphological dependence of counting
      efficiency curves for in vivo lung monitoring of workers, with a particular focus
      on the case of female workers for whom different chest girth and cup size are
      considered. A library of 24 female torsos, with chest girth varying from 85 to
      120 and cup size from A to F, was constructed using mesh and NURBS formats. The
      anatomical realism and usefulness of these models for simulating in vivo counting
      measurements are illustrated and simulations are reported for a typical 4
      germanium (Ge) counting system. A simple analytic formula describing the relation
      between efficiency curves obtained for each female phantom is given. This formula
      uses the mass attenuation coefficient for adipose tissue and two parameters which
      are dependant on lung volume and breast weight. The model is tested against Monte
      Carlo simulated data, experimental data obtained with the Livermore phantom and
      published data. The model correctly describes the efficiency curve and, since the
      parameters depend on the counting geometry, it is shown how to estimate them from
      experimental measurements.

PMID- 21081822
TI  - Development and validation of a magneto-hydrodynamic solver for blood flow
      analysis.
AB  - The objective of this study was to develop a numerical solver to calculate the
      magneto-hydrodynamic (MHD) signal produced by a moving conductive liquid, i.e.
      blood flow in the great vessels of the heart, in a static magnetic field. We
      believe that this MHD signal is able to non-invasively characterize cardiac blood
      flow in order to supplement the present non-invasive techniques for the
      assessment of heart failure conditions. The MHD signal can be recorded on the
      electrocardiogram (ECG) while the subject is exposed to a strong static magnetic
      field. The MHD signal can only be measured indirectly as a combination of the
      heart's electrical signal and the MHD signal. The MHD signal itself is caused by
      induced electrical currents in the blood due to the moving of the blood in the
      magnetic field. To characterize and eventually optimize MHD measurements, we
      developed a MHD solver based on a finite element code. This code was validated
      against literature, experimental and analytical data. The validation of the MHD
      solver shows good agreement with all three reference values. Future studies will
      include the calculation of the MHD signals for anatomical models. We will vary
      the orientation of the static magnetic field to determine an optimized location
      for the measurement of the MHD blood flow signal.

PMID- 21081823
TI  - Characterization of a PET detector head based on continuous LYSO crystals and
      monolithic, 64-pixel silicon photomultiplier matrices.
AB  - The characterization of a PET detector head based on continuous LYSO crystals and
      silicon photomultiplier (SiPM) arrays as photodetectors has been carried out for
      its use in the development of a small animal PET prototype. The detector heads
      are composed of a continuous crystal and a SiPM matrix with 64 pixels in a common
      substrate, fabricated specifically for this project. Three crystals of 12 mm * 12
      mm * 5 mm size with different types of painting have been tested: white, black
      and black on the sides but white on the back of the crystal. The best energy
      resolution, obtained with the white crystal, is 16% FWHM. The detector response
      is linear up to 1275 keV. Tests with different position determination algorithms
      have been carried out with the three crystals. The spatial resolution obtained
      with the center of gravity algorithm is around 0.9 mm FWHM for the three
      crystals. As expected, the use of this algorithm results in the displacement of
      the reconstructed position toward the center of the crystal, more pronounced in
      the case of the white crystal. A maximum likelihood algorithm has been tested
      that can reconstruct correctly the interaction position of the photons also in
      the case of the white crystal.

PMID- 21081824
TI  - Paediatric interventional cardiology: flat detector versus image intensifier
      using a test object.
AB  - Entrance surface air kerma (ESAK) values and image quality parameters were
      measured and compared for two biplane angiography x-ray systems dedicated to
      paediatric interventional cardiology, one equipped with image intensifiers (II)
      and the other one with dynamic flat detectors (FDs). Polymethyl methacrylate
      phantoms of different thicknesses, ranging from 8 to 16 cm, and a Leeds TOR 18-FG
      test object were used. The parameters of the image quality evaluated were noise,
      signal-difference-to-noise ratio (SdNR), high contrast spatial resolution (HCSR)
      and three figures of merit combining entrance doses and signal-to-noise ratios or
      HCSR. The comparisons showed a better behaviour of the II-based system in the low
      contrast region over the whole interval of thicknesses. The FD-based system
      showed a better performance in HCSR. The FD system evaluated would need around
      two times more dose than the II system evaluated to reach a given value of SdNR;
      moreover, a better spatial resolution was measured (and perceived in conventional
      monitors) for the system equipped with flat detectors. According to the results
      of this paper, the use of dynamic FD systems does not lead to an automatic
      reduction in ESAK or to an automatic improvement in image quality by comparison
      with II systems. Any improvement also depends on the setting of the x-ray systems
      and it should still be possible to refine these settings for some of the dynamic
      FDs used in paediatric cardiology.

PMID- 21081825
TI  - Task-oriented quantitative image reconstruction in emission tomography for single
      and multi-subject studies.
AB  - Task-based selection of image reconstruction methodology in emission tomography
      is a critically important step when designing a PET study. This paper concerns
      optimizing, given the measured data of the study only, reconstruction performance
      for a range of quantification tasks: finding the mean radioactivity concentration
      for different regions of interests (ROIs), different ROI sizes and different
      group sizes (i.e. the number of subjects in the PET study). At present, the
      variability of quantification performance of different reconstruction methods,
      according to both the ROI and group sizes, is largely ignored. In this paper, it
      is shown that both the ROI and group size have a tremendous impact on the error
      of the estimator for the task of ROI quantification. A study-specific, task
      oriented and space-variant selection rule is proposed that selects a close to
      optimal estimate drawn from a series of estimates obtained by filtered
      backprojection (FBP) and different OSEM (ordered subset expectation maximization)
      iterations. The optimality criterion is to minimize an estimated mean square
      error (MSE), where the MSE is estimated from the data in the study using the
      bootstrap resampling technique. The proposed approach is appropriate for both
      pixel-level estimates and ROI estimates in single- and multi-subject studies. An
      extensive multi-trial simulation study using a 2D numerical phantom and relevant
      count levels shows that the proposed selection rule can produce quantitative
      estimates that are close to the estimates that minimize the true MSE (where the
      true MSE can only be obtained from many independent Monte-Carlo realizations with
      knowledge of the ground truth). This indicates that with the proposed selection
      rule one can obtain a close to optimal estimate while avoiding the critical step
      of selecting user-defined reconstruction settings (such as an OSEM iteration
      number or the choice between FBP and OSEM). In this initial 2D study, only FBP
      and OSEM reconstruction methods are considered but the proposed selection rule
      should readily generalize to different estimators (i.e. different reconstruction
      algorithms) and 3D imaging.

PMID- 21081826
TI  - Fluence-convolution broad-beam (FCBB) dose calculation.
AB  - IMRT optimization requires a fast yet relatively accurate algorithm to calculate
      the iteration dose with small memory demand. In this paper, we present a dose
      calculation algorithm that approaches these goals. By decomposing the
      infinitesimal pencil beam (IPB) kernel into the central axis (CAX) component and
      lateral spread function (LSF) and taking the beam's eye view (BEV), we
      established a non-voxel and non-beamlet-based dose calculation formula. Both LSF
      and CAX are determined by a commissioning procedure using the collapsed-cone
      convolution/superposition (CCCS) method as the standard dose engine. The proposed
      dose calculation involves a 2D convolution of a fluence map with LSF followed by
      ray tracing based on the CAX lookup table with radiological distance and
      divergence correction, resulting in complexity of O(N(3)) both spatially and
      temporally. This simple algorithm is orders of magnitude faster than the CCCS
      method. Without pre-calculation of beamlets, its implementation is also orders of
      magnitude smaller than the conventional voxel-based beamlet-superposition (VBS)
      approach. We compared the presented algorithm with the CCCS method using
      simulated and clinical cases. The agreement was generally within 3% for a
      homogeneous phantom and 5% for heterogeneous and clinical cases. Combined with
      the 'adaptive full dose correction', the algorithm is well suitable for
      calculating the iteration dose during IMRT optimization.

PMID- 21081827
TI  - NMR relaxation times of trabecular bone-reproducibility, relationships to tissue
      structure and effects of sample freezing.
AB  - Nuclear magnetic resonance (NMR) spectroscopy provides a potential tool for non
      invasive evaluation of the trabecular bone structure. The objective of this study
      was to determine the reproducibility of the NMR relaxation parameters (T(2), Carr
      Purcel-T(2), T(1rho)) for fat and water and relate those to the structural
      parameters obtained by micro-computed tomography (MUCT). Especially, we aimed to
      evaluate the effect of freezing on the relaxation parameters. For storing bone
      samples, freezing is the standard procedure during which the biochemical and
      cellular organization of the bone marrow may be affected. Bovine trabecular bone
      samples were stored at -20  degrees C for 7 days and measured by NMR spectroscopy
      before and after freezing. The reproducibility of NMR relaxation parameters, as
      expressed by the coefficient of variation, ranged from 3.1% to 27.9%. In fresh
      samples, some correlations between NMR and structural parameters (Tb.N, Tb.Sp)
      were significant (e.g. the relaxation rate for T(2) of fat versus Tb.Sp: r = 
      0.716, p < 0.01). Freezing did not significantly change the NMR relaxation times
      but the correlations between relaxation parameters and the MUCT structural
      parameters were not statistically significant after freezing, suggesting some
      nonsystematic alterations of the marrow structure. Therefore, the use of frozen
      bone samples for NMR relaxation studies may provide inferior information about
      the trabecular bone structure.

PMID- 21081828
TI  - Evaluation of a low-cost liquid ultrasound test object for detection of
      transducer artefacts.
AB  - Routine quality control of ultrasound scanners and transducers is important for
      maintaining image quality. Our experience suggests that artefact and uniformity
      evaluation is the most effective single phantom test for detecting equipment
      problems. Current methods for assessing ultrasound images for artefacts have
      important limitations. To overcome these limitations, we have developed a novel,
      low-cost, liquid phantom with a flexible surface for assessing artefacts. A range
      of materials were evaluated and the optimal liquid phantom was found to be a
      water/cornstarch solution contained within a flexible latex balloon. When
      compared to a rigid tissue-mimicking phantom no deficiencies in overall image
      appearance or artefact detection for any transducer model was observed for the
      liquid phantom. With minimal training, reproducible clips were obtained by
      clinical sonographers with low inter- and intra-operator dependence, for a range
      of transducers models. The flexible scanning surface of the liquid phantom allows
      complete rapid coupling of all transducers. Due to its ease of use and low cost
      this liquid phantom appears superior to rigid phantoms for assessment of non
      uniformity artefacts, and should allow clinical practices to perform routine
      artefact assessments of all ultrasound scanners and transducers.

PMID- 21081829
TI  - A Monte Carlo study of a flattening filter-free linear accelerator verified with
      measurements.
AB  - A Monte Carlo model of an Elekta Precise linear accelerator has been built and
      verified by measured data for a 6 and 10 MV photon beam running with and without
      a flattening filter in the beam line. In this study the flattening filter was
      replaced with a 6 mm thick copper plate, provided by the linac vendor, in order
      to stabilize the beam. Several studies have shown that removal of the filter
      improves some properties of the photon beam, which could be beneficial for
      radiotherapy treatments. The investigated characteristics of this new beam
      included output, spectra, mean energy, half value layer and the origin of
      scattered photons. The results showed an increased dose output per initial
      electron at the central axis of 1.76 and 2.66 for the 6 and 10 MV beams,
      respectively. The number of scattered photons from the accelerator head was
      reduced by (31.7 +/- 0.03)% (1 SD) for the 6 MV beam and (47.6 +/- 0.02)% for the
      10 MV beam. The photon energy spectrum of the unflattened beam was softer
      compared to a conventional beam and did not vary significantly with the off-axis
      distance, even for the largest field size (0-20 cm off-axis).

PMID- 21081830
TI  - Application of an M-line-based backprojected filtration algorithm to triple-cone
      beam helical CT.
AB  - To increase the scanning speed of cone-beam CT, a scanning configuration with
      three pairs of x-ray sources and panel detectors was proposed. In this paper, we
      apply the M-line-based backprojected filtration algorithm to this scanning
      configuration and propose a fast implementation for this algorithm. Compared with
      existing implementations, the advantages of our implementation are as follows:
      (1) it can directly reconstruct horizontal slices (i.e. the slices perpendicular
      to the rotation axis), without 3D interpolation; (2) it does not need to
      calculate the backprojection intervals for any point; (3) it has a high degree of
      parallelism and is suitable for acceleration on graphic processing units or other
      parallel systems.

PMID- 21081831
TI  - Analog signal multiplexing for PSAPD-based PET detectors: simulation and
      experimental validation.
AB  - A 1 mm(3) resolution clinical positron emission tomography (PET) system employing
      4608 position-sensitive avalanche photodiodes (PSAPDs) is under development. This
      paper describes a detector multiplexing technique that simplifies the readout
      electronics and reduces the density of the circuit board design. The multiplexing
      scheme was validated using a simulation framework that models the PSAPDs and
      front-end multiplexing circuits to predict the signal-to-noise ratio and flood
      histogram performance. Two independent experimental setups measured the energy
      resolution, time resolution, crystal identification ability and count rate both
      with and without multiplexing. With multiplexing, there was no significant
      degradation in energy resolution, time resolution and count rate. There was a
      relative 6.9 +/- 1.0% and 9.4 +/- 1.0% degradation in the figure of merit that
      characterizes the crystal identification ability observed in the measured and
      simulated ceramic-mounted PSAPD module flood histograms, respectively.

PMID- 21081833
TI  - Relationship between two AMI risk factors: low serum lipoprotein lipase mass and
      hypoadiponectinemia.
AB  - AIM: Recent clinical studies have reported that low lipoprotein lipase mass in
      preheparin serum (s-LpL) and hypoadiponectinemia are important risk factors for
      acute myocardial infarction (AMI). The aim of this study was to elucidate the
      relationship between low s-LpL and hypoadiponectinemia, both of which are risk
      factors for AMI. METHODS: One hundred and thirty-seven male patients with AMI and
      fifty-three males with normal coronary arteries (NCA) were enrolled in the study.
      Coronary risk factors, including s-LpL and serum total adiponectin concentrations
      (t-adiponectin), were compared. RESULTS: Both s-LpL and t-adiponectin were
      significantly lower in patients with AMI than in subjects with NCA (s-LpL, NCA:
      48.1+/-11.0 ng/mL, AMI: 38.9+/-11.1 ng/mL, p< 0.01; t-adiponectin, NCA: 7.7+/-2.9
      ug/mL, AMI: 6.1+/-3.3 ug/mL, p< 0.01). In AMI patients, there was a significant
      positive correlation between s-LpL and t-adiponectin (r=0.46, p< 0.01).
      Furthermore, multivariate analysis indicated that both s-LpL and t-adiponectin
      were independent variables for AMI (s-LpL: p< 0.05, t-adiponectin: p< 0.05).
      CONCLUSION: These results indicate that although low s-LpL and
      hypoadiponectinemia are associated with each other, they are independent risk
      factors for AMI.

PMID- 21081832
TI  - Depot-specific expression of lipolytic genes in human adipose tissues-
      association among CES1 expression, triglyceride lipase activity and adiposity.
AB  - AIM: Adipocyte lipolysis is mediated by a family of triglyceride (TG) lipases
      consisting of hormone-sensitive lipase (LIPE), adipose triglyceride lipase
      (PNPLA2) and carboxylesterase 1 (CES1); however, little is known about the
      relationship between the expression of each gene in different depots and TG
      lipase activity or obesity. METHOD: We measured both mRNA expression levels of
      the lipolytic enzymes (LIPE, PNPLA2 and CES1) and TG lipase activities of biopsy
      samples obtained from subcutaneous, omental and mesenteric adipose tissues of 34
      patients who underwent abdominal surgery. The results were correlated with
      clinical parameters: adiposity measures, parameters for insulin resistance and
      plasma lipid levels. RESULTS: PNPLA2 mRNA levels were slightly higher in omental
      fat than subcutaneous fat. Cytosolic TG lipase activities were positively
      correlated with the mRNA levels of CES1 in subcutaneous fat and mesenteric fat,
      while they were correlated with those of PNPLA2 in omental fat. The mRNA levels
      of LIPE were negatively correlated with various measures of adiposity in
      subcutaneous fat. The mRNA levels of CES1 were positively correlated with various
      measures of adiposity, particularly those estimated by CT in the three depots;
      they were also positively correlated with plasma LDL-cholesterol levels in
      omental fat. In contrast, the mRNA levels of PNPLA2 were not significantly
      associated with adiposity. CONCLUSIONS: The positive correlations of the
      expression of CES1 with cytosolic TG lipase activities as well as with adiposity
      suggest that CES1 is involved in lipolysis, thereby contributing to the
      development of obesity-associated phenotypes. On the other hand, the expression
      of LIPE is negatively correlated with adiposity. These distinct regulatory
      patterns of lipolytic genes may underlie the complex phenotypes associated with
      human obesity.

PMID- 21081834
TI  - Statin treatment decreased serum asymmetric dimethylarginine (ADMA) levels in
      ischemic stroke patients.
AB  - AIM: It remains unclear whether the decrease in the ADMA level associated with
      statin treatment results from the LDL-C-lowering effect or the pleiotropic
      effects of statins. A prospective, controlled study was conducted to examine
      whether statin treatment affects serum ADMA concentrations in ischemic stroke
      patients. METHODS: Consecutive outpatients with non-cardiogenic ischemic stroke
      who had never been treated with statins and whose LDL-cholesterol level was
      higher than 140 mg/dL were enrolled and compared with control patients whose LDL
      cholesterol level was lower than 140 mg/dL. Overall, 114 patients were enrolled
      in the study (56 and 58 in statin-treated and non-statin-treated groups,
      respectively). Patients in the statin group were treated with pravastatin 10
      mg/day (n=15), fluvastatin 20 mg/day (n=14), pitavastatin 1 mg/day (n=14), or
      atorvastatin 10 mg/day (n=13). RESULTS: The serum ADMA concentration and LDL-C
      level were significantly decreased by statin treatment (p=0.003 and p< 0.001,
      respectively), and the ADMA concentration in subjects treated with statins was
      significantly lower than that of the control (p=0.028). Multiple linear
      regression analysis showed that age (beta=0.26, p< 0.05) and statin use (beta=
      0.20, p< 0.05) were independently associated with the ADMA level. CONCLUSIONS: A
      significant relation between statin treatment and decreased levels of ADMA was
      demonstrated in ischemic stroke patients with an adequately controlled lipid
      profile, suggesting the statin treatment might prevent atherosclerotic disease in
      ischemic stroke patients through suppression of ADMA concentration.

PMID- 21081835
TI  - Exploring neuroprotective drug therapies for intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating neurological disorder with high
      mortality and poor prognosis, for which virtually no effective drug therapies are
      available at present. Experimental animal models, based on intrastriatal
      injection of collagenase or autologous blood, have enabled great advances in
      elucidation of cellular/molecular events contributing to brain pathogenesis
      associated with ICH. Many lines of evidence indicate that blood constituents,
      including hemoglobin-derived products as well as proteases such as thrombin, play
      important roles in the pathogenic events. Inflammatory reactions involving
      neutrophils, activated microglia, and production of proinflammatory cytokines
      also constitute a critical aspect of pathology leading to neurodegeneration and
      tissue damage. Efforts are continuing to find drugs that potentially alleviate
      pathological and neurological outcomes of ICH. Various drugs that possess
      antioxidative, anti-inflammatory or neurotrophic/neuroprotective properties have
      been demonstrated to produce therapeutic effects on ICH animal models. Drugs
      already in clinical use such as minocycline, statins, and several nuclear
      receptor ligands are among the list of effective drugs, but whether they also
      show therapeutic efficacy in human ICH patients remains unproven. Here, current
      knowledge of ICH pathogenesis and problems arising with respect to exploration of
      new drug candidates are discussed.

PMID- 21081836
TI  - Insights into sepsis therapeutic design based on the apoptotic death pathway.
AB  - Sepsis remains the leading cause of death in critically ill patients. A major
      problem contributing to sepsis-related high mortality is the lack of effective
      medical treatment. Thus, the key goal in critical care medicine is to develop
      novel therapeutic strategies that will impact favorably on septic patient
      outcome. While it is generally accepted that sepsis is an inflammatory state
      resulting from the systemic response to infection, apoptosis is implicated to be
      an important mechanism of the death of lymphocytes, gastrointestinal and lung
      epithelial cells, and vascular endothelial cells associated with the development
      of multiple organ failure in sepsis. The pivotal role of cell apoptosis is now
      highlighted by multiple studies demonstrating that prevention of cell apoptosis
      can improve survival in clinically relevant animal models of sepsis. In this
      review article, we address the scientific rationale for remedying apoptotic cell
      death in sepsis and propose that therapeutic efforts aimed at blocking cell
      signaling pathways leading to apoptosis may represent an attractive target for
      sepsis therapy.

PMID- 21081837
TI  - Spinal astrocytes as therapeutic targets for pathological pain.
AB  - Development of next-generation analgesics requires a better understanding of the
      molecular and cellular mechanisms underlying pathological pain. Accumulating
      evidence suggests that the activation of glia contributes to the central
      sensitization of pain signaling in the spinal cord. The role of microglia in
      pathological pain has been well documented, while that of astrocytes still
      remains unclear. After peripheral nerve inflammation or injury, spinal microglia
      are initially activated and subsequently sustained activation of astrocytes is
      precipitated, which are implicated in the induction and maintenance of
      pathological pain. Astrocytic activation is caused by the production of
      diffusible factors from primary afferent neurons (neuron-to-astrocyte signals)
      and activated microglia (microglia-to-astrocyte signals). Although astrocyte-to
      neuron signals implicated in pathological pain is poorly understood, activated
      astrocytes, as well as microglia, produce proinflammatory cytokines and
      chemokines, which lead to adaptation of the dorsal horn neurons. Furthermore, it
      has been suggested that glial glutamate transporters in the spinal astrocytes are
      down-regulated in pathological pain and that up-regulation or functional
      enhancement of these transporters prevents pathological pain. This review will
      briefly discuss novel findings on the role of spinal astrocytes in pathological
      pain and their potential as a therapeutic target for novel analgesics.

PMID- 21081838
TI  - Polymorphism of rRNA gene loci in the dog.
AB  - We examined the number of ribosomal gene (rDNA) loci in the metaphase spreads of
      54 dogs by FISH method. We found that in 16 dogs (30%) one or two loci were
      missing. The total number of rDNA loci was varied from 5 to 7 in males and from 4
      to 6 in females. As the male dog consistently bears the rDNA on the Y chromosome,
      the polymorphism of the rDNA locus was ascribed to the absence of autosomal rDNA
      loci. Indeed, the frequency of polymorphism is almost equivalent in both sexes in
      the beagle. In one female beagle dog, remarkable intense fluorescence signals
      were observed at the four autosomal loci, indicating the in situ amplification of
      rDNA.

PMID- 21081839
TI  - Imaging the founder of adult hematopoiesis in the mouse embryo aorta.

PMID- 21081840
TI  - Downregulation of microRNA-29c is associated with hypermethylation of tumor
      related genes and disease outcome in cutaneous melanoma.
AB  - Hypermethylation of the promoter region of tumor-related genes (TRGs) has been
      shown to silence gene expression during melanoma progression, whereas microRNA
      29(miR-29) has been found to downregulate DNA methyltransferases DNMT3A and
      DNMT3B which were shown as essential to the methylation of TRGs. We hypothesized
      that the expression level of miR-29 is associated to TRG methylation status and
      may have prognostic utility in melanoma. AJCC stage I-IV cutaneous melanoma
      paraffin-embedded archival tissue (PEAT) specimens (n=149) were assessed.
      Expression of miR-29 isoforms a, b, and c were analyzed by reverse-transcription
      quantitative real-time polymerase chain reaction(RT-qPCR). Expression of DNMT3A
      and DNMT3B was assessed by immunohistochemistry(IHC) on defined clinically
      annotated tissue microarrays (TMA) of AJCC stage III melanoma lymph node
      metastases. Promoter region CpG island methylation status of RASSF1A, TFPI-2, RAR
      beta, SOCS, GATA4 and genomic repeat sequence MINT17 and MINT31 were previously
      evaluated in melanoma tissues. Only miR-29c isoform expression was correlated to
      advancing AJCC stages in melanoma. miR-29c expression was significantly
      downregulated in AJCC stage IV melanoma tumors compared to primary melanomas.
      Hypermethylation status of TRGs and non-coding MINT loci in different stages of
      melanoma showed an inverse association with miR-29c expression. Overall, an
      increase in miR-29c expression inversely correlated to both DNMT3A and DNMT3B
      protein expression in melanomas. Expression of DNMT3B and miR-29c were
      significantly (p=0.004 and p=0.002, respectively) associated with overall
      survival(OS) in AJCC stage III melanoma patients by multivariate analysis. The
      studies demonstrated that both miR-29c and DNMT3B have significant roles in
      melanoma progression, and may be useful epigenetic biomarkers for disease
      outcome.

PMID- 21081841
TI  - A single-chain triplebody with specificity for CD19 and CD33 mediates effective
      lysis of mixed lineage leukemia cells by dual targeting.
AB  - A single-chain triplebody (sctb) 33-ds16-ds19 comprising two distal single-chain
      Fv fragments (scFvs) specific for the lymphoid antigen CD19 and the myeloid
      antigen CD33 flanking a central scFv specific for CD16, which is the low affinity
      Fc-receptor (FcgammaRIII) present on natural killer cells and macrophages, was
      produced and its properties were investigated. CD33 and CD19 in combination are
      present on acute leukemiablasts with mixed lineage phenotype, but not on normal
      human hematopoietic cells. For comparison, two bispecific scFvs (bsscFvs), ds19
      ds16 and 33-ds16, with monovalent binding to CD19 and CD33, respectively, were
      also studied. The sctb 33-ds16-ds19 specifically interacted with all 3 antigens.
      On the antigen double-positive cell line BV-173, the sctb bound with 2-fold
      greater avidity than bsscFv ds19-ds16 (KD = 21 vs. 42 nM) and with 1.4-fold
      greater avidity than bsscFv 33-ds16 (KD = 29 nM). All 3 fusion proteins had
      similar affinity for CD16 and sufficient thermic stability in human serum. In
      antibody-dependent cellular cytotoxicity (ADCC) reactions with human mononuclear
      cells as effectors, the sctb promoted lysis of BV-173 cells at 23-fold lower
      concentrations than bsscFv ds19-ds16 and at 1.4-fold lower concentrations than
      bsscFv 33-ds16. The sctb also mediated potent ADCC of the antigen double-positive
      mixed lineage leukemia cell line SEM, and the half-maximal concentration EC50 for
      BV-173 cells was 7 pM. Therefore, CD19 and CD33 are present on the surface of
      these leukemic cell lines such that they can be connected by a single sctb
      molecule, permitting the recruitment of NK cells via CD16 and tumor cell lysis.

PMID- 21081843
TI  - Translation termination: new factors and insights.
AB  - In eukaryotes, translation termination requires two eukaryotic release factors,
      eRF1 and eRF3. eRF1 is required for recognition of the stop codon and eRF3
      supports the polypeptide chain release in a GTP dependent manner. Recently,
      several new players in translation termination have been identified. The DEAD-box
      RNA helicase Dbp5 has been shown to support eRF1 in stop codon recognition,
      possibly by proper placement of the release factor on the termination codon. Upon
      its dissociation from eRF1, Dbp5 allows the entry of the second termination
      factor eRF3 into the complex. Further, the Dbp5 interacting protein Gle1 and its
      co-factor inositol hexakisphosphate (IP 6) have been shown to participate in the
      termination process. Dbp5 and Gle1 are well known for their function in mRNA
      export from the nucleus to the cytoplasm. Most interestingly, also the ATP
      binding cassette (ABC) protein Rli1, which requires the mitochondrial and
      cytosolic Fe/S protein biogenesis machineries for its assembly, has recently been
      shown to function in translation termination and recycling of the ribosomes. Rli1
      physically and genetically interacts with both, eRF1 and eRF3. Together, all of
      these novel termination factors modulate in association with the release factors
      more accurate stop codon recognition and these findings broaden our knowledge
      about the final steps in translation.

PMID- 21081842
TI  - Trisomy-21 gene dosage over-expression of miRNAs results in the
      haploinsufficiency of specific target proteins.
AB  - Down syndrome (DS) or Trisomy 21 (Ts21) is caused by the presence of an extra
      copy of all or part of human chromosome 21 (Hsa21) and is the most frequent
      survivable congenital chromosomal abnormality. Bioinformatic annotation has
      established that Hsa21 harbors more than 400 genes, including five microRNA
      (miRNA) genes (miR-99a, let-7c, miR-125b-2, miR-155, and miR-802). MiRNAs are
      endogenous, single-stranded, small non-coding RNA molecules that regulate gene
      expression by interacting with specific recognition elements harbored within the
      3'-untranslated region (3'-UTR) of mRNAs and subsequently target these mRNAs for
      translational repression or destabilization. MiRNA expression profiling, miRNA RT
      PCR, and miRNA in situ hybridization experiments have demonstrated that Hsa21
      derived miRNAs were over-expressed in fetal brain and heart specimens isolated
      from individuals with DS. We now propose that Ts21 gene dosage over-expression of
      Hsa21-derived miRNAs in DS individuals result in the decreased expression of
      specific target proteins (i.e. haploinsufficiency) that contribute, in part, to
      the DS phenotype.

PMID- 21081854
TI  - Endurance training and sprint performance in elite junior cross-country skiers.
AB  - The purpose of the present study was to investigate the relationship between
      aerobic characteristics and sprint skiing performance, and the effects of high
      intensity endurance training on sprint skiing performance and aerobic
      characteristics. Ten male and 5 female elite junior cross-country skiers
      performed an 8-week intervention training period. The intervention group (IG, n =
      7) increased the volume of high-intensity endurance training performed in level
      terrain, whereas the control group (CG, n = 8) continued their baseline training.
      Before and after the intervention period, the skiers were tested for 1.5-km time
      trial performance on roller skis outdoors in the skating technique. Maximal
      oxygen uptake (VO2max) and oxygen uptake at the ventilatory threshold (VO2VT)
      were measured during treadmill running. VO2max and VO2VT were closely related to
      sprint performance (r = ~0.75, both p < 0.008). The IG improved sprint
      performance, VO2max, and VO2VT from pre to posttesting and improved sprint
      performance and VO2VT when compared to the CG (all p < 0.01). This study shows a
      close relationship between aerobic power and sprint performance in cross-country
      skiing and highlights the positive effects of high-intensity endurance training
      in level terrain.

PMID- 21081844
TI  - Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K
      inhibition.
AB  - Caffeine is one of the most frequently ingested neuroactive compounds. All known
      mechanisms of apoptosis induced by caffeine act through cell cycle modulation or
      p53 induction. It is currently unknown whether caffeine-induced apoptosis is
      associated with other cell death mechanisms, such as autophagy. Herein we show
      that caffeine increases both the levels of microtubule-associated protein 1 light
      chain 3-II and the number of autophagosomes, through the use of western blotting,
      electron microscopy and immunocytochemistry techniques. Phosphorylated p70
      ribosomal protein S6 kinase (Thr389), S6 ribosomal protein (Ser235/236), 4E-BP1
      (Thr37/46) and Akt (Ser473) were significantly decreased by caffeine. In
      contrast, ERK1/2 (Thr202/204) was increased by caffeine, suggesting an inhibition
      of the Akt/mTOR/p70S6K pathway and activation of the ERK1/2 pathway. Although
      insulin treatment phosphorylated Akt (Ser473) and led to autophagy suppression,
      the effect of insulin treatment was completely abolished by caffeine addition.
      Caffeine-induced autophagy was not completely blocked by inhibition of ERK1/2 by
      U0126. Caffeine induced reduction of mitochondrial membrane potentials and
      apoptosis in a dose-dependent manner, which was further attenuated by the
      inhibition of autophagy with 3-methyladenine or Atg7 siRNA knockdown.
      Furthermore, there was a reduced number of early apoptotic cells (annexin V
      positive, propidium iodide negative) among autophagy-deficient mouse embryonic
      fibroblasts treated with caffeine than their wild-type counterparts. These
      results support previous studies on the use of caffeine in the treatment of human
      tumors and indicate a potential new target in the regulation of apoptosis.

PMID- 21081855
TI  - Pancreatic lipase inhibition by C-glycosidic flavones Isolated from Eremochloa
      ophiuroides.
AB  - Activity-guided fractionation of a methanolic extract of the leaves of Eremochloa
      ophiuroides (centipede grass) using a pancreatic lipase inhibitory assay led to
      the isolation and identification of a new C-glycosidic flavone, luteolin 6-C-beta
      D-boivinopyranoside (1), as well as eight known compounds. The structures of
      these compounds were established on the basis of interpretation of their
      spectroscopic data. Among these isolates, the C-glycosidic flavones 1-5 showed
      potent inhibitory effects on pancreatic lipase, with IC50 values ranging from
      18.5 +/- 2.6 to 50.5 +/- 3.9 MUM.

PMID- 21081856
TI  - A novel 18-norclerodane diterpenoid from the roots of Tinospora sagittata var.
      yunnanensis.
AB  - A novel 18-nor-clerodane diterpenoid named sagitone (1) was isolated from the 95%
      ethanol extract of dry roots of Tinospora sagittata var. yunnanensis together
      with the five known diterpenoids columbin (2), palmatoside C (3), fibleucin (4),
      tinophylloloside (5) and epitinophylloloside (6). The structure of the new
      compound 1 was determined based on MS, IR, 1D and 2D NMR spectral data. The
      compounds 1-6 did not show significant cytotoxic activity against cancer cell
      lines K562 and HL-60.

PMID- 21081857
TI  - Median lethal dose, antimalarial activity, phytochemical screening and radical
      scavenging of methanolic Languas galanga rhizome extract.
AB  - The methanolic extract of Languas galanga rhizomes was investigated for
      antimalarial activity against Plasmodium berghei (NK65) infections in mice. The
      median lethal dose was determined to ascertain the safety of the extract in ICR
      mice of both sexes. The antimalarial activities during early and established
      infections, as well as the prophylactic activity were evaluated. Phytochemical
      screening and radical scavenging activity of the extract were also investigated
      to elucidate the possible mechanism of the antimalarial properties. The acute
      oral toxicity (LD50) of Languas galanga extract in mice was established to be
      4.998 mg/kg. The extract of Languas galanga rhizomes demonstrated significant
      antiplasmodial activity in all the three models of the antimalarial evaluations.
      Phytochemical screening revealed the presence of some vital antiplasmodial
      constituents such as terpenoids and flavonoids. The extract also exhibited a
      moderate capacity to scavenge the free radicals. The rhizome extract of Languas
      galanga thus possesses antimalarial activity, which explains the rational usage
      of this plant in traditional Malaysian medicine.

PMID- 21081858
TI  - Anti-neoplastic effects of gallic acid, a major component of Toona sinensis leaf
      extract, on oral squamous carcinoma cells.
AB  - Extract of Toona sinensis (TS) has been reported to have various effects on
      cultured cell lines, including anti-proliferative activity in cancer cells. We
      have studied the effects of TS on various human oral squamous carcinoma cell
      lines (HOSCC), including UM1, UM2, SCC-4, and SCC-9. These cell lines were
      treated with TS leaf extract and screened for viability, apoptosis, necrosis, and
      apoptotic gene expression. Normal human oral keratinocytes (NHOK) served as a
      control for cytotoxic assays. Viability of TS-treated HOSCC was reduced, whereas
      that of NHOK was not affected. FACScan analysis revealed that the leaf extract
      induced apoptosis or a combination of apoptosis and necrosis, depending on cell
      type. Microarray and semi-quantitative RT-PCR analysis for apoptotic-related gene
      expression revealed that 3,4,5-trihydroxybenzoic acid (gallic acid, one of the
      major bioactive compounds purified from TS extract) up-regulated pro-apoptotic
      genes such TNF-alpha, TP53BP2, and GADD45A, and down-regulated the anti-apoptotic
      genes Survivin and cIAP1, resulting in cell death. This study suggests that
      gallic acid, the major bioactive compound present, is responsible for the anti
      neoplastic effect of Toona sinensis leaf extract.

PMID- 21081859
TI  - Comparative analysis of headspace volatiles of Chinese Rosa rugosa.
AB  - The floral headspace compounds of Chinese Rosa rugosa germplasms that were
      isolated by an automated headspace sampler with built-in trap, and followed by
      gas chromatography-mass spectrometry for identification and quantification. Up to
      33 volatile compounds were identified from the 23 rose germplasms, including nine
      alcohols, five esters, three alkanes, 10 terpenes, three aldehydes, two ketones,
      and one ether. The main floral components identified were 2-phenylethanol, beta
      citronellol, ethanol, and n-hexane. 'xizi', 'miaofengshan', 'xiangciguo', and
      'tangbai' contained the highest amounts of 2-phenylethanol at 84.66 MUg.g-1, beta
      citronellol at 70.98 MUg.g-1, ethanol at 83.87 MUg.g-1, and n-hexane at 18.23
      MUg.g-1, respectively. 'Rongchengyesheng', 'tanghong', 'xizi', 'miaofengshan',
      and 'baizizhi' could be considered good materials for extracting rose oil and
      breeding new cultivars.

PMID- 21081861
TI  - Liver resection for cystic lesions: a 15-year experience.
AB  - AIM: The aim pf this paper was to review the management strategies in patients
      who had hepatic resection for cystic lesions. If symptomatic, a simple liver cyst
      (SC) is best treated by unroofing. A hydatid cyst (HC) is treated by simple
      cystectomy or pericystectomy. Many procedures have been described for the
      management of complex non-HCS including aspiration, sclerosing therapy, drainage,
      unroofing, and resection. METHODS: A retrospective review of patients who had
      liver resection for cystic lesions between January 1, 1992, and December 31,
      2006. The study was carried out at a University Hospital and a General Community
      Hospital affiliated with a University program. Management strategies were
      detailed, including clinical, biological, and imaging features. Operative
      morbidity and mortality as well as long-term outcome were also assessed. A
      comparison between preoperative and postoperative diagnoses was performed.
      RESULTS: Thirty-three patients (24 women and 9 men) underwent 39 liver
      resections, including 14 left lateral resections, 12 right hemi-hepatectomies, 7
      left hemi-hepatectomies and 6 segmentectomies or wedge resections. The final
      diagnosis included hydatid cyst in 10 patients (30%), cystadenoma in 6 (18%),
      simple cysts in 6 (18%), Caroli's disease in 4 (12%), cystadenocarcinoma in 3
      (9%) and miscellaneous in the 4 remaining (12%). There was no mortality and the
      postoperative morbidity rate was 15%. Long-term follow-up revealed that, besides
      patients with malignancies whose outcome was dismal, overall prognosis was
      positive with efficacious symptom control. CONCLUSION; Accurate preoperative
      diagnosis of liver cystic lesions may be difficult. However, liver resection for
      such lesions is a safe procedure that provides long-term symptomatic control in
      benign disease and may be curative in cases of underlying malignancy. Even if
      nearly 50% of liver cystic lesions treated by resection were either symptomatic
      SC or HC, we recommend en-bloc liver resection for all liver cystic lesions that
      are not clearly parasitic or simple cysts.

PMID- 21081860
TI  - Combining the benefits of homogeneous and heterogeneous catalysis with tunable
      solvents and nearcritical water.
AB  - The greatest advantage of heterogeneous catalysis is the ease of separation,
      while the disadvantages are often limited activity and selectivity. We report
      solvents that use tunable phase behavior to achieve homogeneous catalysis with
      ease of separation. Tunable solvents are homogeneous mixtures of water or
      polyethylene glycol with organics such as acetonitrile, dioxane, and THF that can
      be used for homogeneously catalyzed reactions. Modest pressures of a soluble gas,
      generally CO2, achieve facile post-reaction heterogeneous separation of products
      from the catalyst. Examples shown here are rhodium-catalyzed hydroformylation of
      1-octene and p-methylstyrene and palladium catalyzed C-O coupling to produce o
      tolyl-3,5-xylyl ether and 3,5-di-tert-butylphenol. Both were successfully carried
      out in homogeneous tunable solvents followed by separation efficiencies of up to
      99% with CO2 pressures of 3 MPa. Further examples in tunable solvents are enzyme
      catalyzed reactions such as kinetic resolution of rac-1-phenylethyl acetate and
      hydrolysis of 2-phenylethyl acetate (2PEA) to 2-phenylethanol (2PE). Another
      tunable solvent is nearcritical water (NCW), whose unique properties offer
      advantages for developing sustainable alternatives to traditional processes. Some
      examples discussed are Friedel-Crafts alkylation and acylation, hydrolysis of
      benzoate esters, and water-catalyzed deprotection of N-Boc-protected amine
      compounds.

PMID- 21081862
TI  - Is advanced age a significant risk factor for laparoscopic cholecystectomy?
AB  - AIM: have been a few reports about the outcome of laparoscopic cholecystectomy
      (LC) in the elderly patients. The aim of this study was to assess if morbidity
      and mortality may be increased in the geriatric patients because of high
      incidence of co-morbidity. METHODS: From November 2000 to January 2009, 146
      patients aged 60 years and older who underwent LC were reviewed. Patients were
      placed into two groups by ages: Group A (age = 60-74 years, N.=126), Group B (age
      >= 75, N.=20). RESULTS: One hundred forty six patients underwent LC for benign
      gallbladder disease during this study period There was no difference in operative
      time, ASA, distribution of sex between the two groups. Most patients were treated
      with LC for symptomatic cholelithiasis (82.5%) in both groups. There were sixty
      eight cases (53.96%) in the Group A and 14 (70%) patients in the Group B had co
      morbid diseases (P>0.005). Conversion rates and morbidity was not different
      significantly according to ages for either group (P>0.05). The rate of conversion
      to OC was 9.5% in the Group A and 5% in the Group B. Five complications were
      occurred in the four patients. There was only one bile duct injury in the Group
      A. Conversion rates and postoperative complications were not affected by gender
      and co-morbid diseases (P>0.05) in our study whereas acute cholecystitis were
      found as a risk factor for conversion to open surgery and complications according
      to the cases preoperatively diagnosis (P=0.001). CONCLUSION: LC should be
      recommended with acceptable morbidity and mortality in the elderly. Morbidity and
      conversion to OC are not increased with advanced age even in the extremely
      elderly patients. Acute cholecystitis is correlated with a high risk factor for
      morbidity and conversion to OC.

PMID- 21081863
TI  - Alanine-glutamine dipeptide pretreatment protects rat renal function from small
      intestine ischemia-reperfusion injury.
AB  - AIM: Oxidative injury can cause renal function impairment and failure.
      Glutathione, a free radical scavenger, plays in the kidney a central role in
      oxidant-related events. The aim of this study was to investigate the potential
      beneficial effect of glutamine, a precursor of glutathione in the form of alanine
      glutamine dipeptide (AGD) on small intestine ischemia/ reperfusion (I/R)-induced
      oxidant renal damage in rats. METHODS: Wistar rats were subjected to intestinal
      I/R for 30 min, induced by occlusion of the superior mesenteric artery, followed
      by 60 min reperfusion. AGD pretreatment was given 48 and 24 hours before I/R. At
      the end of the experimental procedure the left kidney was excised and a thin
      tissue slice was obtained for electron microscopy study. Kidney biopsies were
      obtained for malonyl dialdehyde, myeloperoxidase, and glutathione assays.
      RESULTS: Intestinal I/R caused significant oxidative injury in rat renal
      parenchyma consisted of severe alterations observed in subcellular renal
      structures associated with a significant increase in renal malonyl dialdehyde
      levels and a significant decrease in renal glutathione levels. Changes regarding
      subcellular renal structures were ameliorated in AGD pre-treated animals in which
      renal glutathione levels did not decreased significantly. CONCLUSION: Glutamine
      pretreatment in the form of AGD can prevent small bowel I/R-induced oxidant renal
      damage in rats.

PMID- 21081864
TI  - Postmastectomy radiotherapy in breast cancer adjuvant treatment.
AB  - Radiotherapy (RT) plays an important role in the management of locally advanced
      breast cancer (BC). Postmastectomy RT has been shown to significantly reduce the
      risk of loco-regional failure and to improve disease free survival in high-risk
      women with BC. Many trials have shown a significant benefit in local control,
      disease-free and overall survival with the addition of RT for patients with stage
      II and III breast cancer. New perspectives are evaluating multiple biological
      variables that nowadays should be considered in clinical oncology for the
      prescription of postmastectomy radiation therapy. Tailored randomized trials are
      now ongoing to clarify the "grey zone" represented by the intermediate-risk group
      of patients (1-3 lymph nodes involved). We reviewed the major studies offered by
      literature with emphasis on the principal debated issues.

PMID- 21081865
TI  - The role of nodal staging in breast cancer. Past, present and future.
AB  - The axillary nodal status is accepted as the most powerful prognostic tool
      available for early stage breast cancer. In the past radical removal of level I
      and level II lymph nodes at axillary node dissection (ALND) has been the most
      accurate method to assess nodal status, and it is the universal standard;
      however, it is associated with several adverse long-term sequelae. New diagnostic
      technologies have helped to individualize diagnostic evaluation and therapy of
      breast cancer thus improving efficacy and minimizing morbidity of treatment.
      Lymphatic mapping with sentinel lymph node biopsy has emerged as an effective and
      safe alternative to the ALND for detecting axillary metastases. Many issues such
      as indications or technique of performing sentinel node biopsy have been
      evaluated. Multiple studies now confirm that sentinel lymphadenectomy accurately
      stages the axilla and is associated with less morbidity than axillary dissection.
      Blue dye, radiocolloid, or both can be used to identify the sentinel node, and
      several injection techniques may be used successfully. Sentinel node biopsy is
      now minimally invasive, highly accurate method of axillary staging, and has
      replaced routine axillary lymph node dissection as the new standard of care in
      breast cancer. New technologies for axillary nodal staging include innovative
      imaging techniques such as single photon emission computerized tomography (SPECT)
      and modern histopathologic evaluation of sentinel nodes using molecular biologic
      approaches.

PMID- 21081866
TI  - Can axillary lymph node dissection be omitted in patients with breast cancer and
      positive sentinel nodes?
AB  - Sentinel lymph node biopsy has evolved as the surgical procedure of choice for
      women with clinically negative axillae, as part of an effort to move toward the
      less invasive surgical management of breast cancer. Axillary lymph node
      dissection remains the standard of care for patients with a positive axillary
      node and was previously performed on all patients with breast cancer prior to the
      implementation of the sentinel lymph node biopsy. There is, however, controversy
      regarding whether or not all patients with a positive sentinel lymph node need to
      undergo completion axillary dissection for either prognostic or therapeutic
      purposes. This article reviews the literature related to this controversial and
      evolving topic.

PMID- 21081867
TI  - Is surgery always indicated in older women with breast cancer?
AB  - Although surgery has long been considered the main form of curative treatment for
      breast cancer, its use in older women may not always be indicated. Whilst surgery
      has been shown to provide superior local control for breast cancer, there is
      conflicting evidence on whether surgery offers a significant improvement on
      overall survival in these patients. The more indolent tumour biology commonly
      seen in older women with breast cancer, coupled with competing causes of death
      may alter the goals of treatment. The differing needs of older patients should be
      thoroughly assessed to consider their comorbidities, functional status and
      quality of life. A comprehensive geriatric assessment and quality of life
      assessment could identify pretreatment risk factors and guide clinical decision
      making, improving morbidity and prognosis. Alternatives to surgery include
      primary endocrine therapy and primary radiotherapy. Further research is required
      to identify different patient or tumour factors which can be used to
      individualize treatment for breast cancer in older women and to develop holistic
      assessment tools which take into account their individual quality of life,
      geriatric syndromes and functional needs. A dedicated multidisciplinary-led
      clinic may provide a suitable platform for the assessment, review and management
      of this distinctive set of patients.

PMID- 21081868
TI  - [T4 lung cancer: results of surgical treatment].
AB  - Stage T4 non small cell lung cancer (NSCLC) includes an heterogeneous group of
      locally advanced tumors. Results of surgery alone and of chemo and/or
      radiotherapy are disappointing with 5-year survival rates under 10%. Although
      palliative chemo-radiotherapy is the treatment of choice in most cases, radical
      resection has shown prognostic benefit in selected groups of patients with tumor
      infiltrating Superior Vena Cava, carina, aorta, left atrium and vertebral bodies.
      Completeness of resection and absence of mediastinal nodal involvement are
      fundamental conditions for the long-term success of surgery. Increased
      postoperative 30-day mortality and 90-day mortality rates have been reported up
      to 8% and 18% respectively. Neoadjuvant therapy, in the last decades, has shown
      to improve survival of T4 NSCLC patients undergoing surgery and to increase the
      number of patients suitable for surgical resection. Surgical resection is not
      indicated in patients with neoplastic pleural effusion since it is generally
      related to a worse prognosis in such cases. Conversely, patients with T4 tumor
      due to neoplastic satellite nodule in the same lobe are good surgical candidates.
      In some studies, these patients show a significant survival advantage after
      surgical treatment with respect to patients with other types of T4 tumors, when
      no mediastinal nodal involvement is associated.

PMID- 21081869
TI  - A systematic review of the benefit of total parenteral nutrition in the
      management of enterocutaneous fistulas.
AB  - Enterocutaneous fistulas (ECFs) most commonly occur as a complication of
      abdominal surgery but can also occur spontaneously in inflammatory bowel disease,
      diverticulitis, radiation, trauma and sepsis. Although mortality and morbidity
      have reduced in recent years they are still a major cause of concern in patients
      with ECF. Nutritional support is a challenging issue in these patients and a
      major cause of mortality and morbidity. Total parenteral nutrition (TPN) is
      widely used in the management of ECF. In this review the authors examined the
      evidence of the use of TPN in ECF with the aim of determining the indications,
      benefits and outcome of this type of nutritional support in these.

PMID- 21081870
TI  - Shielding assessment of a mobile electron accelerator for intra-operative
      radiotherapy.
AB  - The purpose of this investigation is to measure, characterize and report stray
      photon leakage and scatter radiation measurements from the Mobetron, an
      intraoperative electron linear accelerator designed for use in an operating room
      environment. The study is needed due to recent changes to the shielding design of
      the Mobetron, and also to provide specific information that may be required by
      regulation in various jurisdictions. An analysis is performed on a number of
      manufactured units to deter-mine an average 3D stray photon radiation map. This
      information provides a basis for determining patient-based load restrictions
      and/or additional shielding for the operating room. The data presented evaluates
      the number of procedures for which the Mobetron may be safely operated in a
      typical unshielded operating room.

PMID- 21081871
TI  - Dwell position inaccuracy in the Varian GammaMed HDR ring applicator.
AB  - Varian has issued two Product Notification Letters warning of known inaccuracies
      in dwell positions for their GammaMed HDR ring applicator. This inaccuracy was
      measured for two sets of applicators. Autoexposed radiographs were taken of the
      HDR source at different dwell positions and analyzed per Varian recommendations
      using tools within the BrachyVision treatment planning program. Comparison
      between programmed and actual dwell positions showed the actual positions shifted
      distally by an average of 0.34 cm (0.17 cm-0.59 cm) across all positions in all
      rings. A correction method was developed and tested. During planning, the tip of
      the ring was extrapolated distally beyond its actual position in the patient
      image set and a proximal offset of the same distance was applied to the dwell
      positions. A global shift of 0.3 mm corrected all but the most proximal actual
      dwell position to within +2 mm of the planned position.

PMID- 21081872
TI  - Pretreatment setup verification by cone beam CT in stereotactic radiosurgery:
      phantom study.
AB  - Kilovoltage cone beam computed tomography (CBCT) imaging may be useful in
      verifying patient position in stereotactic radiosurgery (SRS). To evaluate its
      efficacy, we investigated isocenter differences in the radiation beam and CBCT
      with respect to the achievable setup of a conventional frame-based SRS system. A
      verification phantom constructed from two plastic boards and Gafchromic-EBT film
      (4 * 4 cm2) pricked with a pin, was scanned by simulation CT. An isocenter at the
      tip of pin was planned in the treatment planning system and positioned using
      stereotactic coordinates. Star-shot irradiation was performed to evaluate the
      difference between the radiation isocenter and the target (pinhole). CBCT
      rotation of 200 degrees  with a micro multileaf collimator (m3) was performed and
      measured the isocenter difference between CBCT and the target (tip of pin) by
      comparing relative coordinates. Data acquisition was performed 13 times on
      different days and differences were analyzed by calculating mean and standard
      deviation. The mean difference between the radiation beam and the target
      (pinhole) and between radiation beam and CBCT isocenter, were 0.6 +/- 0.2 mm and
      0.8 +/- 0.1 mm, respectively. The setup accuracy of conventional stereotactic
      coordinates and the isocenter accuracy of CBCT complied with AAPM Report No. 54.

PMID- 21081873
TI  - Quality assurance methodology for Varian RapidArc treatment plans.
AB  - With the commercial introduction of the Varian RapidArc, a new modality for
      treatment planning and delivery, the need has arisen for consistent and efficient
      techniques for performing patient-specific quality assurance (QA) tests. In this
      paper we present our methodology for a RapidArc treatment plan QA procedure. For
      our measurements we used a 2D diode array (MapCHECK) embedded at 5 cm water
      equivalent depth in MapPHAN 5 phantom and an Exradin A16 ion chamber placed in
      six different positions in a cylindrical homogeneous phantom (QUASAR). We also
      checked the MUs for the RapidArc plans by using independent software (RadCalc).
      The agreement between Eclipse calculations and MapCHECK/MapPHAN5 measurements was
      evaluated using both absolute distance-to-agreement (DTA) and gamma index with
      10% dose threshold (TH), 3% dose difference (DD), and 3 mm DTA. The average
      agreement was 94.4% for the DTA approach and 96.3% for the gamma index approach.
      In high-dose areas, the discrepancy between calculations and ion chamber
      measurements using the QUASAR phantom was within 4.5% for prostate cases. For the
      RadCalc calculations, we used the average SSD along the arc; however, for some
      patients the agreement for the MUs obtained with RadCalc versus Eclipse was
      inadequate (discrepancy > 5%). In these cases, the plan was divided into partial
      arc plans so that RadCalc could perform a better estimation of the MUs. The
      discrepancy was further reduced to within ~4% using this approach. Regardless of
      the variation in prescribed dose and location of the treated areas, we obtained
      very good results for all patients studied in this paper.

PMID- 21081875
TI  - Accuracy of iView and PIPSpro registration software.
AB  - In radiotherapy, treatment portal images and digitally reconstructed radiographs
      (DRRs) are used to monitor patient setup during clinical routine. The output of
      the registration between the portal image and the reference DRR indicates the
      patient displacement. If the registration is not reliable, the patient
      positioning will not be accurate. The aim of this work is to assess the intrinsic
      and the global accuracy of iView and PIPSpro, two widely used registration
      software programs that implement a manual and a semiautomatic approach,
      respectively. The intrinsic accuracy was tested using a computer generated
      phantom, while the overall accuracy was evaluated registering the portal images
      and the DRRs of an Alderson RANDO phantom. For DRRs, four treatment planning
      systems (TPS) and three CT studies with different slice thicknesses were
      considered.This study demonstrates that the intrinsic accuracy of iView and
      PIPSpro were within 1 pixel and 1 degrees . Using a DRR extracted from a 2 mm CT
      study, the overall accuracy of both methods was about 2 mm and 1 degrees . When
      thicker CT slices are considered, the global accuracy of both methods worsens,
      and differences larger than 1.5 degrees  between the rotation parameters
      estimated with iView and PIPSpro are evident. The results obtained with iView and
      PIPSpro were nearly equivalent.

PMID- 21081874
TI  - Analysis of variation in calibration curves for Kodak XV radiographic film using
      model-based parameters.
AB  - Film calibration is time-consuming work when dose accuracy is essential while
      working in a range of photon scatter environments. This study uses the single
      target single-hit model of film response to fit the calibration curves as a
      function of calibration method, processor condition, field size and depth. Kodak
      XV film was irradiated perpendicular to the beam axis in a solid water phantom.
      Standard calibration films (one dose point per film) were irradiated at 90 cm
      source-to-surface distance (SSD) for various doses (16-128 cGy), depths (0.2,
      0.5, 1.5, 5, 10 cm) and field sizes (5 * 5, 10 * 10 and 20 * 20 cm2). The 8-field
      calibration method (eight dose points per film) was used as a reference for each
      experiment, taken at 95 cm SSD and 5 cm depth. The delivered doses were measured
      using an Attix parallel plate chamber for improved accuracy of dose estimation in
      the buildup region. Three fitting methods with one to three dose points per
      calibration curve were investigated for the field sizes of 5 * 5, 10 * 10 and 20
      * 20 cm2. The inter-day variation of model parameters (background, saturation and
      slope) were 1.8%, 5.7%, and 7.7% (1 sigma) using the 8-field method. The
      saturation parameter ratio of standard to 8-field curves was 1.083 +/- 0.005. The
      slope parameter ratio of standard to 8-field curves ranged from 0.99 to 1.05,
      depending on field size and depth. The slope parameter ratio decreases with
      increasing depth below 0.5 cm for the three field sizes. It increases with
      increasing depths above 0.5 cm. A calibration curve with one to three dose points
      fitted with the model is possible with 2% accuracy in film dosimetry for various
      irradiation conditions. The proposed fitting methods may reduce workload while
      providing energy dependence correction in radiographic film dosimetry. This study
      is limited to radiographic XV film with a Lumisys scanner.

PMID- 21081876
TI  - Impact of multileaf collimator width on intraprostatic dose painting plans for
      dominant intraprostatic lesion of prostate cancer.
AB  - The aim of this study was to investigate the impact of multileaf collimator width
      (MLC-W) on intraprostatic dose painting plans for prostate cancer.Prostate cancer
      maps based on the histopathological findings were superimposed onto simulation CT
      images. Clinical target volume (CTV) 1 was defined as the prostate and the base
      of the seminal vesicles, and CTV2 was defined as the dominant intraprostatic
      lesions. Planning target volume (PTV) 1 and PTV2 were delineated by adding 5 mm
      margins to CTV1 and CTV2, respectively. For each case, two dose painting plans
      were created to deliver 74 Gy to PTV1 and 84 Gy to PTV2 with dynamic multileaf
      collimator technique using two different MLCs: m3 (MLC-W: 3mm) and Millennium (5
      mm). Plans were evaluated by comparing the conformation number (CN), a quantity
      that defines the degree of conformality.The CNs for plans using the m3 and
      Millennium were 0.68 and 0.67 for PTV1 and 0.59 and 0.58 for PTV2, respectively.
      The CNs tended to be higher for a thinner leaf width (p < 0.05).Dosimetric
      advantages associated with smaller leaves were observed. However, differences
      between 3 mm and 5 mm leaf width were relatively small, which suggested that 5 mm
      leaf width would be acceptable in dose painting plans for prostate cancer.

PMID- 21081877
TI  - Assessing a set of optimal user interface parameters for intensity-modulated
      proton therapy planning.
AB  - The purpose was to identify an optimal set of treatment planning parameters and a
      minimal necessary dose matrix resolution for treatment planning with spot-scanned
      protons. Treatment plans based on different combinations of planning parameters
      and dose grid resolutions (DG) were calculated in a homogeneous geometric phantom
      for three cubic targets of different size: 8, 64 and 244 cm3. The proton dose was
      delivered by one single beam. Treatment plans were compared in terms of dose
      profiles parallel to and perpendicular to the central beam axis, as well as by
      dose homogeneity and conformity measures. Irrespective of target size, the dose
      homogeneity and conformity were comparable if the distance between spot layers
      was in the order of the width of a single Bragg peak, and the lateral distance
      between spots did not exceed two times the spot sigma. If the distance between
      spot layers was considerably larger than the width of the Bragg peak, the
      homogeneity index increased. For the small target, this index escalated from
      values around 5% to 12% in extreme, and to more than 20% for the two larger
      targets. Furthermore, the width of the 95% isodose increased. Similar results
      were found for the variation of the parameter determining the lateral spacing
      between proton dose spots. The average difference of dose profiles with respect
      to the profile for a DG of 1mm was below 3% for all considered settings up to a
      DG of 6 mm. However, a DG of less than 2-3 mm is required to keep the maximum
      deviation below this limit. The tests performed in this study are necessary to
      prevent systematic errors from spot-scanning proton therapy planning. A
      separation of dose spots in the dimensions of the Bragg peak in the longitudinal
      direction and no more than two times the spot sigma in the lateral direction were
      found to be adequate for IMPT treatment planning in a homogeneous phantom. A DG
      of 2-3 mm is necessary to accurately resolve the steep dose gradients of proton
      beams.

PMID- 21081878
TI  - The effect and stability of MVCT images on adaptive TomoTherapy.
AB  - Use of helical TomoTherapy-based MVCT imaging for adaptive planning is becoming
      increasingly popular. Treatment planning and dose calculations based on MVCT
      require an image value to electron density calibration to remain stable over the
      course of treatment time. In this work, we have studied the dosimetric impact on
      TomoTherapy treatment plans due to variation in image value to density table
      (IVDT) curve as a function of target degradation. We also have investigated the
      reproducibility and stability of the TomoTherapy MVCT image quality over time.
      Multiple scans of the TomoTherapy "Cheese" phantom were performed over a period
      of five months. Over this period, a difference of 4.7% in the HU values was
      observed in high-density regions while there was no significant variation in the
      image values for the low densities of the IVDT curve. Changes in the IVDT curves
      before and after target replacement were measured. Two clinical treatment sites,
      pelvis and prostate, were selected to study the dosimetric impact of this
      variation. Dose was recalculated on the MVCTs with the planned fluence using IVDT
      curves acquired before and after target change. For the cases studied, target
      replacement resulted in an overall difference of less than 5%, which can be
      significant for hypo-fractionated cases. Hence, it is recommended to measure the
      IVDT curves on a monthly basis and after any major repairs/replacements.

PMID- 21081879
TI  - Characterization of Nyquist ghost in EPI-fMRI acquisition sequences implemented
      on two clinical 1.5 T MR scanner systems: effect of readout bandwidth and echo
      spacing.
AB  - In EPI-fMRI acquisitions, various readout bandwidth (BW) values are used as a
      function of gradients' characteristics of the MR scanner system. Echo spacing
      (ES) is another fundamental parameter of EPI-fMRI sequences, but the employed ES
      value is not usually reported in fMRI studies. Nyquist ghost is a typical EPI
      artifact that can degrade the overall quality of fMRI time series. In this work,
      the authors assessed the basic effect of BW and ES for two clinical 1.5 T MR
      scanner systems (scanner-A, scanner-B) on Nyquist ghost of gradient-echo EPI-fMRI
      sequences. BW range was: scanner-A, 1953-3906 Hz/pixel; scanner-B, 1220-2894
      Hz/pixel. ES range was: scanner-A, scanner-B: 0.75-1.33 ms. The ghost-to-signal
      ratio of time series acquisition (GSRts) and drift of ghost-to-signal ratio
      (DRGSR) were measured in a water phantom. For both scanner-A (93% of variation)
      and scanner-B (102% of variation) the mean GSRts significantly increased with
      increasing BW. GSRts values of scanner-A did not significantly depended on ES. On
      the other hand, GSRts values of scanner-B significantly varied with ES, showing a
      downward trend (81% of variation) with increasing ES. In addition, a GSRts spike
      point at ES = 1.05 ms indicating a potential resonant effect was revealed. For
      both scanners, no significant effect of ES on DRGSR was revealed. DRGSR values of
      scanner-B did not significantly vary with BW, whereas DRGSR values of scanner-A
      significantly depended on BW showing an upward trend from negative to positive
      values with increasing BW. GSRts and DRGSR can significantly vary with BW and ES,
      and the specific pattern of variation may depend on gradients performances, EPI
      sequence calibrations and functional design of radiofrequency coil. Thus, each MR
      scanner system should be separately characterized. In general, the employment of
      low BW values seems to reduce the intensity and temporal variation of Nyquist
      ghost in EPI-fMRI time series. On the other hand, the use of minimum ES value
      might not be entirely advantageous when the MR scanner is characterized by
      gradients with low performances and suboptimal EPI sequence calibration.

PMID- 21081880
TI  - Design and dosimetry characteristics of a commercial applicator system for intra
      operative electron beam therapy utilizing ELEKTA Precise accelerator.
AB  - The design concept and dosimetric characteristics of a new applicator system for
      intraoperative radiation therapy (IORT) are presented in this work. A new hard
      docking commercial system includes polymethylmethacrylate (PMMA) applicators with
      different diameters and applicator end angles and a set of secondary lead
      collimators. A telescopic device allows changing of source-to-surface distance
      (SSD). All measurements were performed for 6, 9, 12 and 18 MeV electron energies.
      Output factors and percentage depth doses (PDD) were measured in a water phantom
      using a plane-parallel ion chamber. Isodose contours and radiation leakage were
      measured using a solid water phantom and radiographic films. The dependence of
      PDD on SSD was checked for the applicators with the smallest and the biggest
      diameters. SSD dependence of the output factors was measured. Hardcopies of PDD
      and isodose contours were prepared to help the team during the procedure on
      deciding applicator size and energy to be chosen. Applicator output factors are a
      function of energy, applicator size and applicator type. Dependence of SSD
      correction factors on applicator size and applicator type was found to be weak.
      The same SSD correction will be applied for all applicators in use for each
      energy. The radiation leakage through the applicators is clinically acceptable.
      The applicator system enables effective collimation of electron beams for IORT.
      The data presented are sufficient for applicator, energy and monitor unit
      selection for IORT treatment of a patient.

PMID- 21081881
TI  - Helical TomoTherapy versus sterotactic Gamma Knife radiosurgery in the treatment
      of single and multiple brain tumors: a dosimetric comparison.
AB  - The objective was to compare the dosimetry of Helical TomoTherapy (TOMO) and
      Gamma Knife (GK) treatment plans for tumor and normal brain in the treatment of
      single and multiple brain tumors. An anthropomorphic Rando Head phantom was used
      to compare the dosimetry of TOMO and GK. Eight brain tumors of various shapes,
      sizes and locations were used to generate 10 plans. The radiation dose was 20 Gy
      prescribed to the 100% isodose line for TOMO plans and to the 50% for the GK
      plans. Dose Volume Histograms for tumor and brain were compared. Equivalent
      Uniform Dose (gEUD), Tumor Control Probability (TCP) and Normal Tissue
      Complication Probability (NTCP) were performed and used for plan comparisons.
      Average minimum, mean, median and maximum tumor doses were 19.93, 27.83, 27.38,
      39.60 Gy for GK and 20.17, 20.60, 20.59, 20.90 Gy for TOMO. Average gEUD values
      for tumor and normal brain were 25.0 and 7.2 Gy for GK and 20.7 and 8.1 Gy for
      TOMO. Conformity indices (CI) were similar for both modalities. Gradient indices
      (GI) were greater for TOMO. A combination plan was also generated using all eight
      tumors. TOMO was able to target all eight tumors simultaneously resulting in mean
      tumor and brain doses of 20.5 and 9.35 Gy, respectively. Due to the maximum limit
      of 50 beams per plan, GK was unable to provide a treatment plan for all eight
      tumors. GK provides an advantage for all tumor sizes with respect to tumor and
      normal brain dose. Clinical studies are needed to correlate these dosimetric
      findings with patient outcomes.

PMID- 21081882
TI  - Dosimetric comparison study between intensity modulated radiation therapy and
      three-dimensional conformal proton therapy for pelvic bone marrow sparing in the
      treatment of cervical cancer.
AB  - The objective was to compare intensity-modulated radiation therapy (IMRT) with 3D
      conformal proton therapy (3DCPT) in the treatment of cervical cancer. In
      particular, each technique's ability to spare pelvic bone marrow (PBM) was of
      primary interest in this study. A total of six cervical cancer patients (3
      postoperative and 3 intact) were planned and analyzed. All plans had uniform 1.0
      cm CTV-PTV margin and satisfied the 95% PTV with 100% isodose (prescription dose
      = 45 Gy) coverage. Dose-volume histograms (DVH) were analyzed for comparison. The
      overall PTV and PBM volumes were 1035.9 +/- 192.2 cc and 1151.4 +/- 198.3 cc,
      respectively. In terms of PTV dose conformity index (DCI) and dose homogeneity
      index (DHI), 3DCPT was slightly superior to IMRT with 1.00 +/- 0.001, 1.01 +/-
      0.02, and 1.10 +/- 0.02, 1.13 +/- 0.01, respectively. In addition, 3DCPT
      demonstrated superiority in reducing lower doses (i.e., V30 or less) to PBM,
      small bowel and bladder. Particularly in PBM, average V10 and V20 reductions of
      10.8% and 7.4% (p = 0.001 and 0.04), respectively, were observed. However, in the
      higher dose range, IMRT provided better sparing (> V30). For example, in small
      bowel and PBM, average reductions in V45 of 4.9% and 10.0% (p = 0.048 and 0.008),
      respectively, were observed. Due to its physical characteristics such as low
      entrance dose, spread-out Bragg peak and finite particle range of protons, 3DCPT
      illustrated superior target coverage uniformity and sparing of the lower doses in
      PBM and other organs. Further studies are, however, needed to fully exploit the
      benefits of protons for general use in cervical cancer.

PMID- 21081883
TI  - Commissioning and quality assurance for a respiratory training system based on
      audiovisual biofeedback.
AB  - A respiratory training system based on audiovisual biofeedback has been
      implemented at our institution. It is intended to improve patients' respiratory
      regularity during four-dimensional (4D) computed tomography (CT) image
      acquisition. The purpose is to help eliminate the artifacts in 4D-CT images
      caused by irregular breathing, as well as improve delivery efficiency during
      treatment, where respiratory irregularity is a concern. This article describes
      the commissioning and quality assurance (QA) procedures developed for this
      peripheral respiratory training system, the Stanford Respiratory Training (START)
      system. Using the Varian real-time position management system for the respiratory
      signal input, the START software was commissioned and able to acquire sample
      respiratory traces, create a patient-specific guiding waveform, and generate
      audiovisual signals for improving respiratory regularity. Routine QA tests that
      include hardware maintenance, visual guiding-waveform creation, auditory sounds
      synchronization, and feedback assessment, have been developed for the START
      system. The QA procedures developed here for the START system could be easily
      adapted to other respiratory training systems based on audiovisual biofeedback.

PMID- 21081884
TI  - Portal dosimetry for pretreatment verification of IMRT plan: a comparison with 2D
      ion chamber array.
AB  - Portal dosimetry (PD) was performed for 181 fields from 14 IMRT plans of various
      clinical sites at gantry zero and source-to-detector distance (SDD) of 100 cm. PD
      was realized using aSi1000 electronic portal imaging device (EPID) and portal
      dose prediction (PDP) algorithm implemented in Eclipse treatment planning system
      (TPS). Agreement of PDP predicted and EPID measured photon fluence/dose
      distribution were evaluated using gamma (gamma) index set at 3% at 3 mm distance
      to point agreement (DTA). Three gamma scaling parameters, maximum gamma
      (gamma(max)), average gamma (gamma(avg)) and percentage of points with gamma <= 1
      (gamma% <= 1) were estimated for each field. An independent measurement was
      carried out using MatriXX 2D ion chamber array with detector plane at 100 cm and
      gamma(max), gamma(avg) and gamma% <= 1 were estimated using OmniPro IMRT
      analyzing software. Effect of extended SDD and gantry rotation on portal
      dosimetry outcome was also investigated for another 45 IMRT fields. PDP predicted
      and EPID measured photon fluence agrees well with overall mean values of
      gamma(max), gamma(avg) and gamma% <= 1 at 2.02, 0.24 and 99.43%, respectively.
      gamma(max) value was lower in 15 MV compared to 6 MV IMRT plan. Independent
      verification using MatriXX showed comparable overall mean values of gamma(avg)
      and gamma% <= 1 at 0.25 and 99.80%. However, in all plans, MatriXX showed
      significantly lower gamma(max) (p < 0.05) with an overall mean value of 1.35. In
      portal dosimetry, compared to gamma values at 100 cm SDD, gamma(max), gamma(avg)
      and gamma% <= 1 values improve from a mean of 0.16, 0.03 and 0.26 at 110 cm SDD
      to 0.35, 0.05 and 0.29 at 140 cm SDD. PD outcome was independent of gantry
      rotation. In conclusion, both MatriXX 2D ion chamber array and portal dosimetry
      showed comparable results and can be use as an alternative to each other for
      relative photon fluence verification.

PMID- 21081885
TI  - A static multi-slit collimator system for scatter reduction in cone-beam CT.
AB  - A multiple-slit collimator (MSC) design was introduced for scatter reduction in
      cone-beam computed tomography (CBCT). Unlike most other collimators, the open and
      closed septa of the proposed MSC are placed in an equi-angular interval on a
      circular track of the central sagittal plane. Therefore, one gantry rotation
      provides only the half of necessary dataset and two gantry rotations are needed
      to obtain full information. During the first gantry rotation, the MSC position
      relative to the source is fixed. For the second rotation, the MSC is rotated by
      the equi-angle interval. We assume signals under the closed septa are totally
      attributed to scatter radiation. Then, scatter contributions under open septa are
      determined by interpolating them.Monte Carlo (MC) simulations for two virtual
      phantoms (one with a simple geometry and the other with two heterogeneities
      simulating the bone and the lung) were performed to evaluate the effectiveness of
      the system. Using the method developed, we could obtain images with significant
      scatter reduction. Contrast ratio (CR) improvement factors were 1.165 in a 2D
      projection view, and 1.210 and 1.223 at the central and peripheral slice of the
      reconstructed CBCT image of the simple geometry phantom.This preliminary study
      demonstrated that the proposed MSC, together with the imaging process technique,
      had a great potential to reduce scatter contribution in CBCT. Further studies
      will be performed to investigate the effect of various factors, such as reducing
      the detector size, increasing the number of history of MC simulation, and
      including many structures with different densities.

PMID- 21081886
TI  - Breast in vivo dosimetry by EPID.
AB  - An electronic portal imaging device (EPID) is an effective detector for in vivo
      transit dosimetry. In fact, it supplies two-dimensional information, does not
      require special efforts to be used during patient treatment, and can supply data
      in real time. In the present paper, a new procedure has been proposed to improve
      the EPID in vivo dosimetry accuracy by taking into account the patient setup
      variations. The procedure was applied to the breast tangential irradiation for
      the reconstruction of the dose at the breast midpoint, Dm. In particular, the
      patient setup variations were accounted for by comparing EPID images versus
      digitally reconstructed radiographies. In this manner, EPID transit signals were
      obtained corresponding to the geometrical projections of the breast midpoint on
      the EPID for each therapy session. At the end, the ratios R between D(m) and the
      doses computed by the treatment planning system (TPS) at breast midpoints,
      D(m,TPS), were determined for 800 therapy sessions of 20 patients. Taking into
      account the method uncertainty, tolerance levels equal to +/- 5% have been
      determined for the ratio R.The improvement of in vivo dosimetry results obtained
      (taking into account patient misalignment) has been pointed out comparing the R
      values obtained with and with-out considering patient setup variations. In
      particular, when patient misalignments were taken into account, the R values were
      within +/- 5% for 93% of the checks; when patient setup variations were not taken
      into account, the R values were within +/- 5% in 72% of the checks. This last
      result points out that the transit dosimetry method overestimates the dose
      discrepancies if patient setup variations are not taken into account for dose
      reconstruction. In this case, larger tolerance levels have to be adopted as a
      trade-off between workload and ability to detect errors, with the drawback being
      that some errors (such as the ones in TPS implementation or in beam calibration)
      cannot be detected, limiting the in vivo dosimetry efficacy.The paper also
      reports preliminary results about the possibility of reconstructing a dose
      profile perpendicular to the beam central axis reaching from the apex to the lung
      and passing through the middle point of the breast by an algorithm, similar to
      the one used for dose reconstruction at breast midpoint. In particular, the
      results have shown an accuracy within +/- 3% for the dose profile reconstructed
      in the breast (excluding the interface regions) and an underestimation of the
      lung dose.

PMID- 21081887
TI  - Monte Carlo investigation of energy response of various detector materials in
      125I and 169Yb brachytherapy dosimetry.
AB  - Relative absorbed-dose energy response correction R for different detector
      materials in water, PMMA and polystyrene phantoms are calculated using Monte
      Carlo-based EGSnrc code system for 125I and 169Yb brachytherapy sources. The
      values of R obtained for 125I source are 1.41, 0.92, 3.97, 0.47, 8.32 and 1.10,
      respectively, for detector materials LiF, Li2B4O7 , A12O3, diamond, silicon diode
      and air. These values are insensitive to source-to-detector distance and phantom
      material. For 169Yb source, R is sensitive to source-to-detector distance for
      detector materials other than air and Li2B4O7. For silicon, R increases from 3 to
      4.23 when depth in water is increased from 0.5 cm to 15 cm. For 169Yb source, the
      values of R obtained for air and Li2B4O7 in PMMA and polystyrene phantoms are
      comparable to that obtained in water. However, LiF, Si and A12O3 show enhanced
      response and diamond shows decreased response in PMMA and polystyrene phantoms
      than in water.

PMID- 21081888
TI  - Providing solid angle formalism for skyshine calculations.
AB  - We detail, derive and correct the technical use of the solid angle variable
      identified in formal guidance that relates skyshine calculations to dose
      equivalent rate. We further recommend it for use with all National Council on
      Radiation Protection and Measurements (NCRP), Institute of Physics and
      Engineering in Medicine (IPEM) and similar reports documented. In general, for
      beams of identical width which have different resulting areas, within +/- 1.0 %
      maximum deviation the analytical pyramidal solution is 1.27 times greater than a
      misapplied analytical conical solution through all field sizes up to 40 * 40 cm2.
      Therefore, we recommend determining the exact results with the analytical
      pyramidal solution for square beams and the analytical conical solution for
      circular beams.

PMID- 21081889
TI  - Use of a matchline dosimetry analysis tool (MDAT) to quantify dose homogeneity in
      the region between abutting tangential and supraclavicular radiation fields.
AB  - In this work, we develop and test a matchline dosimetry analysis tool (MDAT) to
      examine the dose distribution within the abutment region of two or more adjoining
      radiotherapy fields that employ different blocking mechanisms and geometries in
      forming a match. This objective and quantitative tool uses calibrated
      radiographic film to measure the dose in the abutment region, and uses a
      frequency distribution of area versus dose (a dose-area histogram) to visualize
      the spatial dose distribution. We tested the MDAT's clinical applicability and
      parameters by evaluating the dose between adjacent photon fields incident on a
      flat phantom using field-matching techniques employing collimator-jaw and
      multileaf collimator (MLC) configurations. Additionally, we evaluated the dose in
      the abutment regions of four different clinical tangential-breast and
      supraclavicular matching techniques using various combinations of collimator and
      MLC matches. Using the MDAT tool, it was deter-mined that a 1 cm abutment region
      width (centered about the theoretical matchline between fields) is the most
      appropriate width to determine dose homogeneity in a field matching region. Using
      the MDAT, both subtle and large differences were seen between fields that used
      MLCs to form the match, compared to flat edge devices such as collimators and
      external cerrobend blocks. We conclude that the MDAT facilitates a more precise
      evaluation of the distribution of dose within the region of abutment of
      radiotherapy fields.

PMID- 21081890
TI  - A quality assurance procedure to evaluate cone-beam CT image center congruence
      with the radiation isocenter of a linear accelerator.
AB  - A quality assurance (QA) procedure was developed to evaluate the congruence
      between the cone-beam computed tomography (CBCT) image center and the radiation
      isocenter on a Varian Trilogy linac. In contrast to the published QA procedures,
      this method did not require a ball bearing (BB) phantom to be placed exactly at
      the radiation isocenter through precalibrated room lasers or light field
      crosshairs. The only requirement was that the BB phantom be in a stationary
      position near the radiation isocenter during the image acquisition process. The
      radiation isocenter was determined with respect to the center of the BB using a
      Winston-Lutz test. The CBCT image center was found to have excellent short-term
      positional repro-ducibility (i.e., less than 0.1 mm of wobble in each of the x
      (lateral), y (vertical), and z (longitudinal) directions) in 10 consecutive
      acquisitions. Measured over a seven-month period, the CBCT image center deviated
      from the radiation isocenter by 0.40 +/- 0.12 mm (x), 0.43 +/- 0.04 mm (y), and
      0.34 +/- 0.14 mm (z). The z displacement of the 3D CBCT image center was highly
      correlated (rho = 0.997) with that of the 2D kV portal image center. The
      correlation coefficients in the x and y directions were poor (rho = 0.66 and 
      0.35, respectively). Systematic discrepancies were found between the CBCT image
      center and the 2D MV, kV portal image centers. For the linear accelerator
      studied, we detected a 0.8 mm discrepancy between the CBCT image center and the
      MV EPID image center in the anterior-posterior direction.This discrepancy was
      demonstrated in a clinical case study where the patient was positioned with CBCT
      followed by MV portal verification. The results from the new QA procedure are
      useful for guiding high-precision patient positioning in stereotactic body
      radiation therapy.

PMID- 21081892
TI  - Practical quantitative measurement of graticule misalignment relative to
      collimator axis of rotation.
AB  - We design a practical procedure for measuring translational and rotational
      misalignment of graticule with collimator axis of rotation and collimator jaws,
      respectively. The procedure's quantitative results are accurate to less than 0.2
      mm (at isocenter) and do not assume alignment of radiation focal spot with
      collimator axis of rotation. When provided with these quantitative results, the
      manufacturer can custom-adjust graticules to the purchaser's collimator head.

PMID- 21081891
TI  - Comparison of tumor and normal tissue dose for accelerated partial breast
      irradiation using an electronic brachytherapy eBx source and an Iridium-192
      source.
AB  - The objective of this study has been to compare treatment plans for patients
      treated with electronic brachytherapy (eBx) using the Axxent System as adjuvant
      therapy for early stage breast cancer with treatment plans prepared from the same
      CT image sets using an Ir-192 source. Patients were implanted with an
      appropriately sized Axxent balloon applicator based on tumor cavity size and
      shape. A CT image of the implanted balloon was utilized for developing both eBx
      and Ir-192 brachytherapy treatment plans. The prescription dose was 3.4 Gy per
      fraction for 10 fractions to be delivered to 1 cm beyond the balloon surface.
      Iridium plans were provided by the sites on 35 of the 44 patients enrolled in the
      study. The planning target volume coverage was very similar when comparing
      sources for each patient as well as between patients. There were no statistical
      differences in mean %V100. The percent of the planning target volume in the high
      dose region was increased with eBx as compared with Iridium (p < 0.001). The mean
      maximum calculated skin and rib doses did not vary greatly between eBx and
      Iridium. By contrast, the doses to the ipsilateral lung and the heart were
      significantly lower with eBx as compared with Iridium (p < 0.0001). The total
      nominal dwell times required for treatment can be predicted by using a
      combination of the balloon fill volume and planned treatment volume (PTV). This
      dosimetric comparison of eBx and Iridium sources demonstrates that both forms of
      balloon-based brachytherapy provide comparable dose to the planning target
      volume. Electronic brachytherapy is significantly associated with increased dose
      at the surface of the balloon and decreased dose outside the PTV, resulting in
      significantly increased tissue sparing in the heart and ipsilateral lung.

PMID- 21081893
TI  - Improved volumetric imaging in tomosynthesis using combined multiaxial sweeps.
AB  - This study explores the volumetric reconstruction fidelity attainable using
      tomosynthesis with a kV imaging system which has a unique ability to rotate
      isocentrically and with multiple degrees of mechanical freedom. More
      specifically, we seek to investigate volumetric reconstructions by combining
      multiple limited-angle rotational image acquisition sweeps. By comparing these
      reconstructed images with those of a CBCT reconstruction, we can gauge the
      volumetric fidelity of the reconstructions. In surgical situations, the described
      tomosynthesis-based system could provide high-quality volumetric imaging without
      requiring patient motion, even with rotational limitations present. Projections
      were acquired using the Digital Integrated Brachytherapy Unit, or IBU-D. A
      phantom was used which contained several spherical objects of varying contrast.
      Using image projections acquired during isocentric sweeps around the phantom,
      reconstructions were performed by filtered backprojection. For each image
      acquisition sweep configuration, a contrasting sphere is analyzed using two
      metrics and compared to a gold standard CBCT reconstruction. Since the
      intersection of a reconstructed sphere and an imaging plane is ideally a circle
      with an eccentricity of zero, the first metric presented compares the effective
      eccentricity of intersections of reconstructed volumes and imaging planes. As
      another metric of volumetric reconstruction fidelity, the volume of one of the
      contrasting spheres was determined using manual contouring. By comparing these
      manually delineated volumes with a CBCT reconstruction, we can gauge the
      volumetric fidelity of reconstructions. The configuration which yielded the
      highest overall volumetric reconstruction fidelity, as determined by effective
      eccentricities and volumetric contouring, consisted of two orthogonally-offset 60
      degrees  L-arm sweeps and a single C-arm sweep which shared a pivot point with
      one the L-arm sweeps. When compared to a similar configuration that lacked the C
      arm component, it is shown that the C-arm improves the delineation of volumes
      along the transverse axis. The results described herein suggest that volumetric
      reconstruction using multiple, unconstrained orthogonal sweeps can provide an
      improvement compared with traditional cone beam CT using standard axial
      rotations.

PMID- 21081894
TI  - Verification of IMRT dose calculations using AAA and PBC algorithms in dose
      buildup regions.
AB  - The purpose of this comparative study was to test the accuracy of anisotropic
      analytical algorithm (AAA) and pencil beam convolution (PBC) algorithms of
      Eclipse treatment planning system (TPS) for dose calculations in the low- and
      high-dose buildup regions. AAA and PBC algorithms were used to create two
      intensity-modulated radiotherapy (IMRT) plans of the same optimal fluence
      generated from a clinically simulated oropharynx case in an in-house fabricated
      head and neck phantom. The TPS computed buildup doses were compared with the
      corresponding measured doses in the phantom using thermoluminescence dosimeters
      (TLD 100). Analysis of dose distribution calculated using PBC and AAA shows an
      increase in gamma value in the dose buildup region indicating large dose
      deviation. For the surface areas of 1, 50 and 100 cm2, PBC overestimates doses as
      compared to AAA calculated value in the range of 1.34%-3.62% at 0.6 cm depth,
      1.74%-2.96% at 0.4 cm depth, and 1.96%-4.06% at 0.2 cm depth, respectively. In
      high-dose buildup region, AAA calculated doses were lower by an average of -7.56%
      (SD = 4.73%), while PBC was overestimated by 3.75% (SD = 5.70%) as compared to
      TLD measured doses at 0.2 cm depth. However, at 0.4 and 0.6 cm depth, PBC
      overestimated TLD measured doses by 5.84% (SD = 4.38%) and 2.40% (SD = 4.63%),
      respectively, while AAA underestimated the TLD measured doses by -0.82% (SD =
      4.24%) and -1.10% (SD = 4.14%) at the same respective depth. In low-dose buildup
      region, both AAA and PBC overestimated the TLD measured doses at all depths
      except -2.05% (SD = 10.21%) by AAA at 0.2 cm depth. The differences between AAA
      and PBC at all depths were statistically significant (p < 0.05) in high-dose
      buildup region, whereas it is not statistically significant in low-dose buildup
      region. In conclusion, AAA calculated the dose more accurately than PBC in
      clinically important high-dose buildup region at 0.4 cm and 0.6 cm depths. The
      use of an orfit cast increases the dose buildup effect, and this buildup effect
      decreases with depth.

PMID- 21081897
TI  - Obituary: Gail D. Adams, Ph.D. 1918-2010.

PMID- 21081896
TI  - Daily image-guided localization for neuroblastoma.
AB  - The purpose was to quantify the setup margin for pediatric patients with neuro
      blastoma using cone beam CT imaging (CBCT) and ultrasound localization. Ten
      patients, with a median age of 4.3 years (1.8 to 7.9) underwent daily
      pretreatment localization CBCT and every other day post-treatment CBCT to
      calculate interfractional and intrafraction movement. Localization was based on
      CBCT to treatment planning CT registration in the lumbar spine region. Each
      subject was treated in the supine position under IV general anesthesia using
      intensity-modulated radiation therapy. Patients were repositioned based on the
      daily pretreatment CBCT. Required setup margins based on inter- and intrafraction
      positioning errors were calculated based on weekly and daily imaging scenarios.
      Four patients had ultra-sound localization of the kidneys performed before the
      CBCT. Correlation between daily CBCT and ultrasound was investigated. A lateral,
      longitudinal and vertical setup margin of 5.4, 5.6, and 5.9 mm is required
      without daily CBCT. When daily CBCT was incorporated, the setup margin was
      reduced to 1.5, 2.1, and 1.7 mm. There was no correlation between the suggested
      ultrasound shifts and the shifts based on the CBCT. Daily localization based on
      CBCT of the lumbar spine can reduce the required setup margin for neuroblastoma
      patients, thereby reducing normal tissue exposure for this young patient
      population. The internal margin needs further investigation before PTV reduction
      can be made. Ultrasound localization was highly variable and not correlated to
      CBCT shifts.

PMID- 21081899
TI  - Smaug assembles an ATP-dependent stable complex repressing nanos mRNA translation
      at multiple levels.
AB  - The nanos (nos) mRNA encodes the posterior determinant of the Drosophila embryo.
      Translation of the RNA is repressed throughout most of the embryo by the protein
      Smaug binding to Smaug recognition elements (SREs) in the 3' UTR. Translation is
      locally activated at the posterior pole by Oskar. This paper reports that the
      SREs govern the time- and ATP-dependent assembly of an exceedingly stable
      repressed ribonucleoprotein particle (RNP) in embryo extract. Repression can be
      virtually complete. Smaug and its co-repressor Cup as well as Trailer hitch and
      the DEAD box protein Me31B are part of the repressed RNP. The initiation factor
      eIF4G is specifically displaced, and 48S pre-initiation complex formation is
      inhibited. However, later steps in translation initiation are also sensitive to
      SRE-dependent inhibition. These data confirm several previously untested
      predictions of a current model for Cup-dependent repression but also suggest that
      the Cup model by itself is insufficient to explain translational repression of
      the nos RNA. In the embryo extract, recombinant Oskar relieves translational
      repression and deadenylation by preventing Smaug's binding to the SREs.

PMID- 21081900
TI  - Minicircle DNA-based gene therapy coupled with immune modulation permits long
      term expression of alpha-L-iduronidase in mice with mucopolysaccharidosis type I.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease characterized
      by mutations to the alpha-L-iduronidase (IDUA) gene resulting in inactivation of
      the IDUA enzyme. The loss of IDUA protein results in the progressive accumulation
      of glycosaminoglycans within the lysosomes resulting in severe, multi-organ
      system pathology. Gene replacement strategies have relied on the use of viral or
      nonviral gene delivery systems. Drawbacks to these include laborious production
      procedures, poor efficacy due to plasmid-borne gene silencing, and the risk of
      insertional mutagenesis. This report demonstrates the efficacy of a
      nonintegrating, minicircle (MC) DNA vector that is resistant to epigenetic gene
      silencing in vivo. To achieve sustained expression of the immunogenic IDUA
      protein we investigated the use of a tissue-specific promoter in conjunction with
      microRNA target sequences. The inclusion of microRNA target sequences resulted in
      a slight improvement in long-term expression compared to their absence. However,
      immune modulation by costimulatory blockade was required and permitted for IDUA
      expression in MPS I mice that resulted in the biochemical correction of pathology
      in all of the organs analyzed. MC gene delivery combined with costimulatory
      pathway blockade maximizes safety, efficacy, and sustained gene expression and is
      a new approach in the treatment of lysosomal storage disease.

PMID- 21081901
TI  - Controlled extracellular matrix degradation in breast cancer tumors improves
      therapy by trastuzumab.
AB  - Extracellular matrix (ECM) in solid tumors affects the effectiveness of
      therapeutics through blocking of intratumoral diffusion and/or physical masking
      of target receptors on malignant cells. In immunohistochemical studies of tumor
      sections from breast cancer patients and xenografts, we observed colocalization
      of ECM proteins and Her2/neu, a tumor-associated antigen that is the target for
      the widely used monoclonal antibody trastuzumab (Herceptin). We tested whether
      intratumoral expression of the peptide hormone relaxin (Rlx) would result in ECM
      degradation and the improvement of trastuzumab therapy. As viral gene delivery
      into epithelial tumors with extensive tumor ECM is inefficient, we used a
      hematopoietic stem cell (HSC)-based approach to deliver the Rlx gene to the
      tumor. In mouse models with syngeneic breast cancer tumors, HSC-mediated
      intratumoral Rlx expression resulted in a decrease of ECM proteins and enabled
      control of tumor growth. Moreover, in a model with Her2/neu-positive BT474-M1
      tumors and more treatment-refractory tumors derived from HCC1954 cells, we
      observed a significant delay of tumor growth when trastuzumab therapy was
      combined with Rlx expression. Our results have implications for antibody therapy
      of cancer as well as for other anticancer treatment approaches that are based on
      T-cells or encapsulated chemotherapy drugs.

PMID- 21081902
TI  - Poly(oligo-D-arginine) with internal disulfide linkages as a cytoplasm-sensitive
      carrier for siRNA delivery.
AB  - Small interfering RNA (siRNA) has emerged as a therapeutic strategy for various
      diseases due to its target-specific gene silencing; however, its relatively high
      molecular weight, negative charge, and low stability hamper in vitro and in vivo
      applications. Approaches to overcome those drawbacks have relied on nonviral
      siRNA carriers based on cationic polymers or peptides. Nevertheless, cationic
      polymer-based siRNA carriers have yet to resolve intrinsic problems such as
      cytotoxicity and immunogenicity. An environment-sensitive carrier was recently
      proposed to enhance siRNA bioactivity and to reduce the carrier safety issues.
      Only a few studies, however, have shown cytoplasm-sensitive dissociation of the
      polyplex. In the present study, we clearly demonstrated decondensation of
      siRNA/poly(oligo-D-arginine) polyplex in the cytoplasm in response to
      intracellular glutathione (GSH) and the enhanced bioactivity of siRNA against
      VEGF (siVEGF) used as a model both in vitro and in an animal model. Reducible
      poly(oligo-D-arginine) (rPOA) rapidly dissociated in the cytoplasm, resulting in
      fast siRNA release to its target location while maintaining siRNA bioactivity
      both in vitro and in vivo.

PMID- 21081903
TI  - Inhibition of the inflammatory cytokine TNF-alpha increases adenovirus activity
      in ovarian cancer via modulation of cIAP1/2 expression.
AB  - Oncolytic adenoviruses show promise as a cancer treatment. However, they generate
      acute inflammatory responses with production of cytokines, including tumor
      necrosis factor-alpha (TNF-alpha). We investigated whether inhibition of TNF
      alpha augments efficacy of the E1A CR2-deleted adenovirus dl922-947 in ovarian
      cancer. dl922-947 induced transcription of TNF-alpha and its downstream signaling
      targets interleukin-6 and -8 (IL-6 and IL-8) in ovarian cancer cells. In vitro,
      RNAi-mediated knockdown of TNF-alpha reduced production of multiple inflammatory
      cytokines after infection and increased ovarian cancer cell sensitivity to virus
      cytotoxicity, as did treatment with the anti-TNF-alpha antibody infliximab. In
      vivo, stable knockdown of TNF-alpha in IGROV-1 xenografts increased the
      anticancer activity of dl922-947. In addition, inhibition of TNF-alpha using
      monoclonal antibodies also improved dl922-947 efficacy. This increased efficacy
      resulted from suppression of cellular inhibitor of apoptosis-1 and -2 (cIAP1 and
      cIAP2) transcription in malignant cells and a consequent increase in caspase
      mediated apoptosis. These findings suggest that TNF-alpha acts as a survival
      factor in adenovirus-infected cells. Combining TNF-alpha inhibition with
      oncolytic adenoviruses could improve antitumor activity in clinical trials.

PMID- 21081904
TI  - HSV delivery of a ligand-regulated endogenous ion channel gene to sensory neurons
      results in pain control following channel activation.
AB  - Persistent pain remains a tremendous health problem due to both its prevalence
      and dearth of effective therapeutic interventions. To maximize pain relief while
      minimizing side effects, current gene therapy-based approaches have mostly
      exploited the expression of pain inhibitory products or interfered with
      pronociceptive ion channels. These methods do not enable control over the timing
      or duration of analgesia, nor titration to analgesic efficacy. Here, we describe
      a gene therapy strategy that potentially overcomes these limitations by providing
      exquisite control over therapy with efficacy in clinically relevant models of
      inflammatory pain. We utilize a herpes simplex viral (HSV) vector (vHGlyRalpha1)
      to express a ligand-regulated chloride ion channel, the glycine receptor (GlyR)
      in targeted sensory afferents; the subsequent exogenous addition of glycine
      provides the means for temporal and spatial control of afferent activity, and
      therefore pain. Use of an endogenous inhibitory receptor not normally present on
      sensory neurons both minimizes immunogenicity and maximizes therapeutic
      selectivity.

PMID- 21081905
TI  - Vaccine-induced T cells provide partial protection against high-dose rectal
      SIVmac239 challenge of rhesus macaques.
AB  - Despite enormous efforts by the scientific community, an effective HIV vaccine
      remains elusive. To further address to what degree T cells in absence of
      antibodies may protect against simian immunodeficiency virus (SIV) disease
      progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee
      derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a
      serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239.
      Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara
      (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge
      with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed
      only a modest reduction of viral loads, their overall survival was improved, in
      association with a substantial protection from the loss of CD4(+) T cells. In
      addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to
      levels below detection within weeks after challenge. These data strongly suggest
      that T cells, while unable to affect SIV acquisition upon high-dose rectal
      infection, can reduce disease progression. Induction of potent T-cell responses
      should thus remain a component of our efforts to develop an efficacious vaccine
      to HIV-1.

PMID- 21081906
TI  - Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs
      following liver gene therapy using AAV vectors.
AB  - Developing adeno-associated viral (AAV)-mediated gene therapy for hemophilia A
      (HA) has been challenging due to the large size of the factor VIII (FVIII)
      complementary DNA and the concern for the development of inhibitory antibodies to
      FVIII in HA patients. Here, we perform a systematic study in HA dogs by
      delivering a canine FVIII (cFVIII) transgene either as a single chain or two
      chains in an AAV vector. An optimized cFVIII single chain delivered using AAV
      serotype 8 (AAV8) by peripheral vein injection resulted in a dose-response with
      sustained expression of FVIII up to 7% (n = 4). Five HA dogs administered two
      chain delivery using either AAV8 or AAV9 via the portal vein expressed long-term,
      vector dose-dependent levels of FVIII activity (up to 10%). In the two-chain
      approach, circulating cFVIII antigen levels were more than fivefold higher than
      activity. Notably, no long-term immune response to FVIII was observed in any of
      the dogs (1/9 dogs had a transient inhibitor). Long-term follow-up of the dogs
      showed a remarkable reduction (>90%) of bleeding episodes in a combined total of
      24 years of observation. These data demonstrate that both approaches are safe and
      achieve dose-dependent therapeutic levels of FVIII expression, which supports
      translational studies of AAV-mediated delivery for HA.

PMID- 21081907
TI  - Lentiviral vector platform for production of bioengineered recombinant
      coagulation factor VIII.
AB  - Patients with hemophilia A present with spontaneous and sometimes life
      threatening bleeding episodes that are treated using blood coagulation factor
      VIII (fVIII) replacement products. Although effective, these products have
      limited availability worldwide due to supply limitations and product costs, which
      stem largely from manufacturing complexity. Current mammalian cell culture
      manufacturing systems yield around 100 ug/l of recombinant fVIII, with a per cell
      production rate of 0.05 pg/cell/day, representing 10,000-fold lesser production
      than is achieved for other similar-sized recombinant proteins (e.g. monoclonal
      antibodies). Expression of human fVIII is rate limited by inefficient transport
      through the cellular secretory pathway. Recently, we discovered that the
      orthologous porcine fVIII possesses two distinct sequence elements that enhance
      secretory transport efficiency. Herein, we describe the development of a
      bioengineered fVIII product using a novel lentiviral-driven recombinant protein
      manufacturing platform. The combined implementation of these technologies yielded
      production cell lines that biosynthesize in excess of 2.5 mg/l of recombinant
      fVIII at the rate of 9 pg/cell/day, which is the highest level of recombinant
      fVIII production reported to date, thereby validating the utility of both
      technologies.

PMID- 21081908
TI  - Low-dose aspirin-induced ulceration is attenuated by aspirin-phosphatidylcholine:
      a randomized clinical trial.
AB  - OBJECTIVES: Relative contributions of local and systemic mechanisms of upper
      gastrointestinal (GI) injury following aspirin are unknown. Studies suggest that
      aspirin's GI risk is age related and that gastroprotection may be needed at
      therapy initiation. We determined acute gastroduodenal erosion and ulceration
      following low-dose aspirin and aspirin-phosphatidylcholine complex (PL2200) in
      subjects at risk of aspirin ulcers. METHODS: In a randomized, single blind,
      multicenter active-controlled study, we compared upper GI damage of aspirin and
      PL2200 in healthy subjects (n=204, ages 50-74 years) following 7 days of oral 325
      mg once daily, immediate release aspirin or PL2200. RESULTS: Overall, 42.2% of
      aspirin-treated subjects developed multiple erosions and/or ulcers, whereas 22.2%
      treated with PL2200 developed such damage (P=0.0027). Gastroduodenal ulcers were
      observed in 17.6% of aspirin-treated compared with 5.1% of subjects treated with
      PL2200 (P=0.0069). CONCLUSIONS: Low-dose aspirin induced a surprisingly high
      incidence of acute gastroduodenal ulcers in at risk subjects, highlighting that
      aspirin's upper GI risk begins early and may require gastroprotection. Local
      mechanisms of GI protection are important as aspirin's preassociation with
      surface-active phospholipids significantly reduced mucosal damage. PL2200 may be
      an attractive alternative or complement to proton pump inhibitors in older
      patients who are at risk of aspirin-induced ulceration. Longer-term studies
      assessing clinical GI events are desirable to confirm the clinical GI safety
      profile of PL2200.

PMID- 21081909
TI  - Overlap between folding and functional energy landscapes for adenylate kinase
      conformational change.
AB  - Enzyme function is often dependent on fluctuations between inactive and active
      structural ensembles. Adenylate kinase isolated from Escherichia coli (AK(e)) is
      a small phosphotransfer enzyme in which interconversion between inactive (open)
      and active (closed) conformations is rate limiting for catalysis. AK(e) has a
      modular three-dimensional architecture with two flexible substrate-binding
      domains that interact with the substrates AMP, ADP and ATP. Here, we show by
      using a combination of biophysical and mutagenic approaches that the
      interconversion between open and closed states of the ATP-binding subdomain
      involves partial subdomain unfolding/refolding in an otherwise folded enzyme.
      These results provide a novel and, possibly general, molecular mechanism for the
      switch between open and closed conformations in AK(e).

PMID- 21081910
TI  - Anisotropic structure of the order parameter in FeSe(0.45)Te(0.55) revealed by
      angle-resolved specific heat.
AB  - The central issues for understanding iron (Fe)-based superconductors are the
      symmetry and structure of the superconducting gap. So far the experimental data
      and theoretical models have been highly controversial. Some experiments favor two
      or more constant or nearly constant gaps, others indicate strong anisotropy and
      yet others suggest gap zeros ('nodes'). A unique method for addressing this
      issue, and one of very few methods that are bulk and angle resolved, is measuring
      the electronic-specific heat in a rotating magnetic field. In this study, we
      present the first such measurement for an Fe-based high-T(c) superconductor. We
      observed a fourfold oscillation of the specific heat as a function of the in
      plane magnetic field direction. Our results are consistent with the expectations
      for an extended s-wave model, with a significant gap anisotropy on the electron
      pockets and the gap minima along the GammaM (Fe-Fe bond) direction.

PMID- 21081911
TI  - Novel sialic acid derivatives lock open the 150-loop of an influenza A virus
      group-1 sialidase.
AB  - Influenza virus sialidase has an essential role in the virus' life cycle. Two
      distinct groups of influenza A virus sialidases have been established, that
      differ in the flexibility of the '150-loop', providing a more open active site in
      the apo form of the group-1 compared to group-2 enzymes. In this study we show,
      through a multidisciplinary approach, that novel sialic acid-based derivatives
      can exploit this structural difference and selectively inhibit the activity of
      group-1 sialidases. We also demonstrate that group-1 sialidases from drug
      resistant mutant influenza viruses are sensitive to these designed compounds.
      Moreover, we have determined, by protein X-ray crystallography, that these
      inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with
      our molecular modelling prediction. This is the first direct proof that compounds
      may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and
      other group-1 sialidase-containing viruses, based on an open 150-loop
      conformation of the enzyme.

PMID- 21081912
TI  - Dilatancy in the flow and fracture of stretched colloidal suspensions.
AB  - Concentrated particulate suspensions, commonplace in the pharmaceutical, cosmetic
      and food industries, display intriguing rheology. In particular, the dramatic
      increase in viscosity with strain rate (shear thickening and jamming), which is
      often observed at high-volume fractions, is of practical and fundamental
      importance. Yet, manufacture of these products and their subsequent dispensing
      often involves flow geometries substantially different from that of simple shear
      flow experiments. In this study, we show that the elongation and breakage of a
      filament of a colloidal fluid under tensile loading is closely related to the
      jamming transition seen in its shear rheology. However, the modified flow
      geometry reveals important additional effects. Using a model system with nearly
      hard-core interactions, we provide evidence of surprisingly strong
      viscoelasticity in such a colloidal fluid under tension. With high-speed
      photography, we also directly observe dilatancy and granulation effects, which
      lead to fracture above a critical elongation rate.

PMID- 21081913
TI  - Threat of invasive pests from within national borders.
AB  - Predicting and ranking potential invasive species present significant challenges
      to researchers and biosecurity agencies. Here we analyse a worldwide database of
      pest species assemblages to generate lists of the top 100 insect pests most
      likely to establish in the United States and each of its 48 contiguous states.
      For the United States as a whole, all of the top 100 pest species have already
      established. Individual states however tend to have many more 'gaps' with most
      states having at least 20 species absent from their top 100 list. For all but one
      state, every exotic pest species currently absent from a state's top 100 can be
      found elsewhere in the contiguous United States. We conclude that the immediate
      threat from known invasive insect pests is greater from within the United States
      than without. Our findings have potentially significant implications for
      biosecurity policy, emphasizing the need to consider biosecurity measures beyond
      established national border interventions.

PMID- 21081914
TI  - Monolithic nonlinear pulse compressor on a silicon chip.
AB  - Projected demands in information bandwidth have resulted in a paradigm shift from
      electrical to optical interconnects. Switches, modulators and wavelength
      converters have all been demonstrated on complementary metal-oxide semiconductor
      compatible platforms, and are important for all optical signal and information
      processing. Similarly, pulse compression is crucial for creating short pulses
      necessary for key applications in high-capacity communications, imaging and
      spectroscopy. In this study, we report the first demonstration of a chip-scale,
      nanophotonic pulse compressor on silicon, operating by nonlinear spectral
      broadening from self-phase modulation in a nanowire waveguide, followed by
      temporal compression with an integrated dispersive element. Using a low input
      peak power of 10 W, we achieve compression factors as high as 7 for 7 ps pulses.
      This compact and efficient device will enable ultrashort pulse sources to be
      integrated with systems level photonic circuits necessary for future
      optoelectronic networks.

PMID- 21081915
TI  - Drug export and allosteric coupling in a multidrug transporter revealed by
      molecular simulations.
AB  - Multidrug resistance is a serious problem in current chemotherapy. The efflux
      system largely responsible for resistance in Escherichia coli contains the drug
      transporter, AcrB. The structures of AcrB were solved in 2002 as the symmetric
      homo-trimer, and then in 2006 as the asymmetric homo-trimer. The latter suggested
      a functionally rotating mechanism. Here, by molecular simulations of the AcrB
      porter domain, we uncovered allosteric coupling and the drug export mechanism in
      the AcrB trimer. Allosteric coupling stabilized the asymmetric structure with one
      drug molecule bound, which validated the modelling. Drug dissociation caused a
      conformational change and stabilized the symmetric structure, providing a unified
      view of the structures reported in 2002 and 2006. A dynamic study suggested that,
      among the three potential driving processes, only protonation of the drug-bound
      protomer can drive the functional rotation and simultaneously export the drug.

PMID- 21081916
TI  - Field-induced water electrolysis switches an oxide semiconductor from an
      insulator to a metal.
AB  - Water is composed of two strong electrochemically active agents, H(+) and OH(-)
      ions, but has not been used as an active electronic material in oxide
      semiconductors. In this study, we demonstrate that water-infiltrated nanoporous
      glass electrically switches an oxide semiconductor from insulator to metal. We
      fabricated a field-effect transistor structure on an oxide semiconductor,
      SrTiO(3), using water-infiltrated nanoporous glass-amorphous 12CaO.7Al(2)O(3)-as
      the gate insulator. Positive gate voltage, electron accumulation, water
      electrolysis and electrochemical reduction occur successively on the SrTiO(3)
      surface at room temperature. This leads to the formation of a thin (~3 nm) metal
      layer with an extremely high electron concentration (10(15)-10(16) cm(-2)), which
      exhibits exotic thermoelectric behaviour. The electron activity of water as it
      infiltrates nanoporous glass may find many useful applications in electronics or
      in energy storage.

PMID- 21081917
TI  - The structure of superantigen complexed with TCR and MHC reveals novel insights
      into superantigenic T cell activation.
AB  - Superantigens (SAgs) are bacterial toxins that interact with immunoreceptors, T
      cell receptor (TCR) and major histocompatibility complex (MHC) class II,
      conventionally through the variable beta-domain of TCR (TCRVbeta). They induce a
      massive release of cytokines, which can lead to diseases such as food poisoning
      and toxic shock syndrome. In this study, we report the X-ray structure of the
      ternary complex between staphylococcal enterotoxin H (SEH) and its human
      receptors, MHC class II and TCR. The structure demonstrates that SEH
      predominantly interacts with the variable alpha-domain of TCR (TCRValpha), which
      is supported by nuclear magnetic resonance (NMR) analyses. Furthermore, there is
      no contact between MHC and TCR upon complex formation. Structural analyses
      suggest that the major contact points to TCRValpha are conserved among other
      bacterial SAgs. Consequently, a new dimension of SAg biology emerges, suggesting
      that in addition to the conventional interactions with the TCRVbeta domain, SAgs
      can also activate T cells through the TCRValpha domain.

PMID- 21081918
TI  - A plasmid-based multigene expression system for mammalian cells.
AB  - The introduction of heterologous genetic information, particularly of multiple
      genes, into mammalian cells is a key technology in contemporary experimental
      biological research. The coexpression of fluorescently tagged sensors is required
      to simultaneously analyse multiple parameters in living cells and the
      coexpression of several proteins is necessary to manipulate cell fate in stem
      cell biology. Current technologies for multigene expression in mammalian cells
      are inefficient, inflexible and time-consuming. In this paper we describe
      MultiLabel, a novel and highly efficient modular plasmid-based eukaryotic
      expression system. Independent expression vectors are assembled by a Cre/LoxP
      reaction into a plasmid with multiple expression cassettes. MultiLabel enables
      rapid construction of multigene expression vectors for the single-step creation
      of transiently or stably transfected mammalian cells.

PMID- 21081919
TI  - Quantum metrology for gravitational wave astronomy.
AB  - Einstein's general theory of relativity predicts that accelerating mass
      distributions produce gravitational radiation, analogous to electromagnetic
      radiation from accelerating charges. These gravitational waves (GWs) have not
      been directly detected to date, but are expected to open a new window to the
      Universe once the detectors, kilometre-scale laser interferometers measuring the
      distance between quasi-free-falling mirrors, have achieved adequate sensitivity.
      Recent advances in quantum metrology may now contribute to provide the required
      sensitivity boost. The so-called squeezed light is able to quantum entangle the
      high-power laser fields in the interferometer arms, and could have a key role in
      the realization of GW astronomy.

PMID- 21081920
TI  - Mechanism of signal transduction of the LOV2-Jalpha photosensor from Avena
      sativa.
AB  - Fusion proteins containing blue-light-activable protein domains possess great
      potential as molecular switches in cell signalling. This has recently been
      impressively demonstrated by connecting the light oxygen voltage LOV2-Jalpha
      protein domain of A. sativa (AsLOV2-Jalpha) with the Rac1-GTPase, responsible for
      regulating the morphology and motility of metazoan cells. However, a target
      oriented development of fusion proteins in conjunction with this photosensor is
      still very challenging, because a detailed understanding of its signal
      transduction pathway on a molecular level is still lacking. Here, we show through
      molecular dynamics simulation that, after formation of the cysteinyl-flavin
      mononucleotide (FMN) adduct, the signalling pathway begins with a rotational
      reorientation of the residue glutamine 1029 adjacent to the FMN chromophore,
      transmitting stress through the Ibeta strand towards the LOV2-Jalpha interface.
      This then results in the breakage of two H-bonds, namely, glutamic acid 1034
      Gln995 and aspartic acid (Asp) 1056-Gln1013, at opposite sides of the interface
      between the Jalpha helix and the LOV2 domain, ultimately leading to a disruption
      of Jalpha helix from the LOV2 core.

PMID- 21081921
TI  - A matter of timing and precision.

PMID- 21081923
TI  - Genetic interactions reveal the evolutionary trajectories of duplicate genes.
AB  - The characterization of functional redundancy and divergence between duplicate
      genes is an important step in understanding the evolution of genetic systems.
      Large-scale genetic network analysis in Saccharomyces cerevisiae provides a
      powerful perspective for addressing these questions through quantitative
      measurements of genetic interactions between pairs of duplicated genes, and more
      generally, through the study of genome-wide genetic interaction profiles
      associated with duplicated genes. We show that duplicate genes exhibit fewer
      genetic interactions than other genes because they tend to buffer one another
      functionally, whereas observed interactions are non-overlapping and reflect their
      divergent roles. We also show that duplicate gene pairs are highly imbalanced in
      their number of genetic interactions with other genes, a pattern that appears to
      result from asymmetric evolution, such that one duplicate evolves or degrades
      faster than the other and often becomes functionally or conditionally
      specialized. The differences in genetic interactions are predictive of
      differences in several other evolutionary and physiological properties of
      duplicate pairs.

PMID- 21081924
TI  - Quantitative analysis of the transcription control mechanism.
AB  - Gene transcription requires a sequence of promoter state transitions, including
      chromatin remodeling, assembly of the transcription machinery, and clearance of
      the promoter by RNA polymerase. The rate-limiting steps in this sequence are
      regulated by transcriptional activators that bind at specific promoter elements.
      As the transition kinetics of individual promoters cannot be observed, the
      identity of the activator-controlled steps has remained a matter of speculation.
      In this study, we investigated promoter chromatin structure, and the intrinsic
      noise of expression over a wide range of expression values for the PHO5 gene of
      yeast. Interpretation of our results with regard to a stochastic model of
      promoter chromatin remodeling and gene expression suggests that the regulatory
      architecture of the gene expression process is measurably reflected in its
      intrinsic noise profile. Our chromatin structure and noise analyses indicate that
      the activator of PHO5 transcription stimulates the rates of promoter nucleosome
      disassembly, and assembly of the transcription machinery after nucleosome
      removal, but no other rates of the expression process.

PMID- 21081925
TI  - mRNA turnover rate limits siRNA and microRNA efficacy.
AB  - The microRNA pathway participates in basic cellular processes and its discovery
      has enabled the development of si/shRNAs as powerful investigational tools and
      potential therapeutics. Based on a simple kinetic model of the mRNA life cycle,
      we hypothesized that mRNAs with high turnover rates may be more resistant to RNAi
      mediated silencing. The results of a simple reporter experiment strongly
      supported this hypothesis. We followed this with a genome-wide scale analysis of
      a rich corpus of experiments, including RT-qPCR validation data for thousands of
      siRNAs, siRNA/microRNA overexpression data and mRNA stability data. We find that
      short-lived transcripts are less affected by microRNA overexpression, suggesting
      that microRNA target prediction would be improved if mRNA turnover rates were
      considered. Similarly, short-lived transcripts are more difficult to silence
      using siRNAs, and our results may explain why certain transcripts are inherently
      recalcitrant to perturbation by small RNAs.

PMID- 21081926
TI  - Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70
      gene prognosis signature.
AB  - BACKGROUND: overexpression of HER-2 is observed in 15-25% of breast cancers, and
      is associated with increased risk of recurrence. Current guidelines recommend
      trastuzumab and chemotherapy for most HER-2-positive patients. However, the
      majority of patients does not recur and might thus be overtreated with adjuvant
      systemic therapy. We investigated whether the 70-gene MammaPrint signature
      identifies HER-2-positive patients with favourable outcome. METHODS: in all, 168
      T1-3, N0-1, HER-2-positive patients were identified from a pooled database,
      classified by the 70-gene signature as good or poor prognosis, and correlated
      with long-term outcome. A total of 89 of these patients did not receive adjuvant
      chemotherapy. RESULTS: in the group of 89 chemotherapy-naive patients, after a
      median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast
      cancer-specific deaths occurred. The 70-gene signature classified 20 (22%)
      patients as good prognosis, with 10-year distant disease-free survival (DDFS) of
      84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The
      estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7,
      P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific
      survival (BCSS), respectively. In multivariate analysis adjusted for known
      prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03)
      and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively.
      INTERPRETATION: the 70-gene prognosis signature is an independent prognostic
      indicator that identifies a subgroup of HER-2-positive early breast cancer with a
      favourable long-term outcome.

PMID- 21081927
TI  - Gene expression profiles of human melanoma cells with different invasive
      potential reveal TSPAN8 as a novel mediator of invasion.
AB  - BACKGROUND: Metastatic melanoma requires early detection, being treatment
      resistant. However, the earliest events of melanoma metastasis, and especially of
      dermal invasion, remain ill defined. RESULTS AND METHODS: Gene expression
      profiles of two clonal subpopulations, selected from the same human melanoma cell
      line, but differing in ability to cross the dermal-epidermal junction in skin
      reconstructs, were compared by oligonucleotide microarray. Of 26 496 cDNA probes,
      461 were differentially expressed (>2-fold; P< 0.001), only 71 genes being
      upregulated in invasive cells. Among them, TSPAN8, a tetraspanin not yet
      described in melanoma, was upregulated at mRNA and protein levels in melanoma
      cells from the invasive clone, as assessed by RT-PCR, flow cytometry and western
      blot analysis. Interestingly, TSPAN8 was the only tetraspanin in which
      overexpression correlated with invasive phenotype. Flow cytometry of well-defined
      melanoma cell lines confirmed that TSPAN8 was exclusively expressed by invasive,
      but not non-invasive melanoma cells or normal melanocytes. Immunohistochemistry
      revealed that TSPAN8 was expressed by melanoma cells in primary melanomas and
      metastases, but not epidermal cells in healthy skin. The functional role of
      TSPAN8 was demonstrated by silencing endogenous TSPAN8 with siRNA, reducing
      invasive outgrowth from tumour spheroids within matrigel without affecting cell
      proliferation or survival. CONCLUSION: TSPAN8 expression may enable melanoma
      cells to cross the cutaneous basement membrane, leading to dermal invasion and
      progression to metastasis. TSPAN8 could be a promising target in early detection
      and treatment of melanoma.

PMID- 21081928
TI  - Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of
      five mononucleotide repeats.
AB  - BACKGROUND: microsatellite instability (MSI) is commonly screened using a panel
      of two mononucleotide and three dinucleotide repeats as recommended by a
      consensus meeting on MSI tumours held at the National Cancer Institute (Bethesda,
      MD, USA). According to these recommendations, tumours are classified as MSI-H
      when at least two of the five microsatellite markers show instability, MSI-L when
      only one marker shows instability and MSS when none of the markers show
      instability. Almost all MSI-H tumours are characterised by alterations in one of
      the four major proteins of the mismatch repair (MMR) system (MLH1, MSH2, MSH6 or
      PMS2) that renders them MMR deficient, whereas MSI-L and MSS tumours are
      generally MMR proficient. However, tumours from patients with a pathogenic
      germline mutation in MSH6 can sometimes present an MSI-L phenotype with the NCI
      panel. The MSH6 protein is not involved in the repair of mismatches of two
      nucleotides in length and consequently the three dinucleotide repeats of the NCI
      panel often show stability in MSH6-deficient tumours. METHODS: a pentaplex panel
      comprising five mononucleotide repeats has been recommended as an alternative to
      the NCI panel to determine tumour MSI status. Several studies have confirmed the
      sensitivity, specificity and ease of use of the pentaplex panel; however, its
      sensitivity for the detection of MSH6-deficient tumours is so far unknown. Here,
      we used the pentaplex panel to evaluate MSI status in 29 tumours known to harbour
      an MSH6 defect. RESULTS: MSI-H status was confirmed in 15 out of 15 (100%) cases
      where matching normal DNA was available and in 28 out of 29 (97%) cases where
      matching DNA was not available or was not analysed. CONCLUSION: these results
      show that the pentaplex assay efficiently discriminates the MSI status of tumours
      with an MSH6 defect.

PMID- 21081929
TI  - A Phase 1b/2 trial of mapatumumab in patients with relapsed/refractory non
      Hodgkin's lymphoma.
AB  - BACKGROUND: we conducted a multicentre Phase 1b/2 trial to evaluate the safety
      and efficacy of mapatumumab, a fully human agonistic monoclonal antibody to the
      tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) in
      patients with relapsed non-Hodgkin's lymphoma (NHL). METHODS: forty patients with
      relapsed or refractory NHL were treated with either 3 or 10 mg kg(-1) mapatumumab
      every 21 days. In the absence of disease progression or prohibitive toxicity,
      patients received a maximum of six doses. RESULTS: mapatumumab was well
      tolerated, with no patients experiencing drug-related hepatic or other dose
      limiting toxicity. Three patients with follicular lymphoma (FL) experienced
      clinical responses, including two with a complete response and one with a partial
      response. Immunohistochemistry staining of the TRAIL-R1 suggested that strong
      staining in tumour specimens did not appear to be a requirement for mapatumumab
      activity in FL. CONCLUSIONS: mapatumumab is safe and has promising clinical
      activity in patients with FL.

PMID- 21081930
TI  - Salt intake and gastric cancer risk according to Helicobacter pylori infection,
      smoking, tumour site and histological type.
AB  - BACKGROUND: Although salt intake is considered a probable risk factor for gastric
      cancer, relevant studies have provided heterogeneous results, and the magnitude
      of the association has not been accurately quantified. METHODS: To quantify
      gastric cancer risk in relation to dietary salt exposure according to
      Helicobacter pylori infection status and virulence, smoking, tumour site, and
      histological type, we evaluated 422 gastric cancer cases and 649 community
      controls. Salt exposure was estimated in the year before the onset of symptoms
      through: sodium intake (estimated by a food frequency questionnaire (FFQ)); main
      food items/groups contributing to dietary sodium intake; visual analogical scale
      for salt intake preference; use of table salt; and duration of refrigerator
      ownership. RESULTS: Comparing subjects with the highest with those with the
      lowest salt exposure (3rd vs 1st third), sodium intake (OR=2.01, 95% CI: 1.16
      3.46), consumption of food items with high contribution to sodium intake
      (OR=2.54, 95% CI: 1.56-4.14) and salt intake evaluated by visual analogical scale
      (OR=1.83, 95% CI: 1.28-2.63) were associated with an increased gastric cancer
      risk. Subjects owning a refrigerator for >50 years had a lower risk for gastric
      cancer (OR=0.28, 95% CI: 0.14-0.57). These associations were observed regardless
      of H. pylori infection status and virulence, smoking, tumour site or histological
      type. CONCLUSION: Our results support the view that salt intake is an important
      dietary risk factor for gastric cancer, and confirms the evidence of no
      differences in risk according to H. pylori infection and virulence, smoking,
      tumour site and histological type.

PMID- 21081931
TI  - Risk of second cancers after the diagnosis of Merkel cell carcinoma in
      Scandinavia.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of
      the skin that has been associated with a new tumour virus, the MCC polyomavirus.
      METHODS: To investigate whether MCC may have a shared aetiology with other
      cancers, we investigated the risk of second cancers after the diagnosis of MCC
      using the national cancer registries in Denmark, Norway and Sweden. RESULTS: The
      overall cancer incidence was increased among patients diagnosed with MCC compared
      with the general population in these countries (79 secondary cancers total,
      Standardized Incidence Ratio (SIR) 1.38 (95% confidence interval (CI): 1.10
      1.72); 49 secondary cancer in females, SIR 1.7 (95% CI: 1.29-2.25); 30 secondary
      cancers in males and SIR 1.05 (95% CI: 0.73-1.5)). There were significantly
      increased incidence ratios for non-melanoma skin cancers (34 secondary cancers,
      SIR 8.35 (95% CI: 5.97-11.68)), melanoma of skin (6 secondary cancers, SIR 4.29
      (95% CI: 1.93-9.56)) and laryngeal cancer (2 secondary cancers, SIR 9.51 (95% CI:
      2.38-38)). The SIRs for these three cancer sites were also elevated on
      restricting the follow-up to cancers occurring at least one year after MCC
      diagnosis. CONCLUSIONS: Patients diagnosed with MCC are at increased risk of a
      second cancer, particularly, other skin cancers. Conceivable explanations include
      the impact of increased surveillance of the skin and shared causative factors,
      for example, ultraviolet light exposure or MCC polyomavirus infection.

PMID- 21081932
TI  - Association of angiopoietin-2, C-reactive protein and markers of obesity and
      insulin resistance with survival outcome in colorectal cancer.
AB  - BACKGROUND: This study investigated the relationship of obesity, insulin
      resistance, inflammation and angiogenesis with cancer progression and survival in
      a colorectal cancer cohort. METHODS: Clinical and pathological data, along with
      anthropometric and follow-up data, were collected from 344 consecutive colorectal
      cancer patients. Serum samples at diagnosis were analysed by immunoassay for
      adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF
      A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C
      peptide. RESULTS: Serum Ang-2 and VEGF-A levels increased with tumour T stage
      (P=0.007 and P=0.025, respectively) and N stage (P=0.02 and P=0.03,
      respectively), and correlated with CRP levels (r=0.43, P<0.001 and r=0.23,
      P<0.001, respectively). Angiopoietin-2 correlated with C-peptide (r=0.14,
      P=0.007) and VEGF-A with IGF-1 in males (r=0.25, P=0.001). Kaplan-Meier analysis
      showed that patients with high serum levels of CRP and Ang-2 had significantly
      reduced survival (both P<=0.001). After adjusting for tumour stage and age, Ang-2
      remained a significant predictor of survival. The CRP levels were inversely
      associated with survival in American Joint Committee on Cancer stage II patients
      (P=0.038), suggesting that CRP could be used to support treatment decisions in
      this subgroup. Serum markers and anthropometric measures of obesity correlated
      with each other, but not with survival. CONCLUSION: Our study supports the
      concept that obesity-related inflammation, rather than obesity itself, is
      associated with colorectal cancer progression and survival. The study confirms
      serum Ang-2 as a predictive marker for outcome of colorectal cancer.

PMID- 21081933
TI  - Tricyclic antidepressants and the incidence of certain cancers: a study using the
      GPRD.
AB  - BACKGROUND: Several studies suggest links between cancer and tricyclic
      antidepressant use. METHODS: A case-control study using the General Practice
      Research Database examined whether previous tricyclic usage was associated with
      reduced incidence of brain (with glioma as a sub-category), breast, colorectal,
      lung and prostate cancers. Conditional logistic regression adjusted for age,
      gender, general practice, depression, smoking, body mass index, alcohol use and
      non-steroidal anti-inflammatory drug use. RESULTS: A total of 31 953 cancers were
      identified, each matched with up to two controls. We found a statistically
      significant reduction in tricyclic prescriptions compared with controls in glioma
      (odds ratio (OR) =0.59, 95% confidence interval (CI)=0.42-0.81) and colorectal
      cancer patients (OR=0.84, CI=0.75-0.94). These effects were dose-dependent (P
      values for trend, glioma=0.0005, colorectal=0.001) and time-dependant (P-values
      for trend glioma=0.0005, colorectal=0.0086). The effects were cancer-type
      specific, with lung, breast and prostate cancers largely unaffected by
      antidepressant use. CONCLUSION: The biologically plausible, specific and dose-
      and time-dependant inverse association that we have found suggests that
      tricyclics may have potential for prevention of both colorectal cancer and
      glioma.

PMID- 21081937
TI  - What is clinical utility and why should we care?

PMID- 21081934
TI  - Ras and Raf pathways in epidermis development and carcinogenesis.
AB  - The epidermis is the outermost layer of the body and protects it from
      environmental insults. This crucial function is sustained by a continuous process
      of self-renewal involving the carefully balanced proliferation and
      differentiation of progenitor cells constantly replacing the mature cells at the
      surface of the epidermis. Genetic changes in the signalling pathways controlling
      keratinocyte proliferation and differentiation disrupt this balance and lead to
      pathological changes including carcinogenesis. This review discusses the role of
      Ras, an oncogene critically involved in the development of skin neoplasia, and
      its downstream effector Raf in epidermal homeostasis and tumourigenesis. In
      particular, we will focus on the recently established role of Raf-1 as the
      decisive element that, by restraining keratinocyte differentiation, allows the
      development and maintenance of Ras-driven tumours.

PMID- 21081940
TI  - Evidence-based medicine in the era of biomarkers: teaching a new dog old tricks?

PMID- 21081941
TI  - Regulation of laboratory-developed tests: the case for utilizing professional
      associations.

PMID- 21081942
TI  - An outsider's viewpoint: the FDA should regulate clinical pharmacogenetic/genomic
      tests, but....

PMID- 21081943
TI  - Establishing clinical utility of pharmacogenetic tests in the post-FDAAA era.
AB  - The US Food and Drug Administration (FDA) Amendments Act of 2007, when fully
      implemented, will offer new sources of evidence and new regulatory mechanisms
      during the postmarket phase of drug life. If artfully and carefully applied,
      these new capabilities could help resolve problems that have long impeded the
      clinical translation of pharmacogenomics.

PMID- 21081944
TI  - Payers and the assessment of clinical utility for companion diagnostics.
AB  - The decision makers who approve or deny payment for health-care services review
      many new technologies. Reimbursement for companion diagnostics for expensive
      drugs ("personalized medicine") is already under close policy scrutiny, in line
      with long-standing concerns about overuse of diagnostic tests. Evaluation of
      diagnostic tests adds some complexities to the payer's comparative-effectiveness
      evaluation for drugs alone. Currently, decision-making frameworks suitable for
      companion diagnostics are being developed for practical application by payer
      policy makers.

PMID- 21081945
TI  - The clinical utility of precision medicine: properly assessing the value of
      emerging diagnostic tests.
AB  - Assessments of the clinical utility of biomarkers and genomic tests often ignore
      individual utility and fail to account for downstream changes to the care
      delivery model. Tests that identify outliers are often undervalued in favor of
      those that help direct treatment for the "average" patient. By reducing
      uncertainty, these tests also enable lower-cost providers and even patients to
      assume increased responsibility for care in more convenient and affordable
      settings.

PMID- 21081946
TI  - Demonstrating utility of pharmacogenetics in pediatric populations:
      methodological considerations.
AB  - Interpretable and meaningful pharmacogenetic data are dependent on accurate
      characterization of phenotypes. High-quality reports are critical, and important
      clinical data must not be omitted. Adequate funding to fully support dedicated
      program personnel is essential to meet this requirement because an "employee
      driven" network that funds its surveillance clinicians is likely to be more
      effective than a voluntary surveillance model in capturing both adequate numbers
      of cases and well-characterized clinical data for rigorous phenotyping.

PMID- 21081947
TI  - Ethical considerations in CYP2D6 genotype testing for codeine-prescribed
      breastfeeding mothers.
AB  - In this issue, Madadi et al. report on interviews with codeine-prescribed
      breastfeeding mothers concerning preferences and attitudes toward receiving their
      CYP2D6 genotype and overall study findings. We address three sets of ethics
      questions raised by this article. Should genetic information be disclosed to
      research participants in genetic research? What should clinicians take into
      account when considering this genetic test in managing infant opioid toxicity
      risk? What conditions support or hinder the integration of genetic information
      into patient care?

PMID- 21081949
TI  - Branched fatty acids inhibit the biosynthesis of menaquinone in Helicobacter
      pylori.

PMID- 21081951
TI  - Fundamental functionality: recent developments in understanding the structure
      activity relationships of lantibiotic peptides.
AB  - There has been great interest in the development of extremely potent
      antibacterial lantibiotic peptides for medicinal use and in food preservation. Of
      central importance to this endeavor is a strong understanding of which parts of
      the peptides are required for activity and which parts are expendable. Nisin,
      lacticin 481, nukacin ISK-1, mersacidin, lacticin 3147 and haloduracin represent
      many different types of lantibiotic peptides. In recent years, considerable
      advances toward understanding the structure-activity relationship of each of
      these lantibiotic systems have been achieved. This review will focus on the
      individual systems and the valuable information obtained from the many mutants
      produced.

PMID- 21081950
TI  - Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone
      family of metabolites: hydroxylation of 1-deoxypentalenic acid mediated by
      CYP105D7 (SAV_7469) of Streptomyces avermitilis.
AB  - Pentalenic acid (1) has been isolated from many Streptomyces sp. as a co
      metabolite of the sesquiterpenoid antibiotic pentalenolactone and related natural
      products. We have previously reported the identification of a 13.4-kb gene
      cluster in the genome of Streptomyces avermitilis implicated in the biosynthesis
      of the pentalenolactone family of metabolites consisting of 13 open reading
      frames. Detailed molecular genetic and biochemical studies have revealed that at
      least seven genes are involved in the biosynthesis of the newly discovered
      metabolites, neopentalenoketolactone, but no gene specifically dedicated to the
      formation of pentalenic acid (1) was evident in the same gene cluster. The wild
      type strain of S. avermitilis, as well as its derivatives, mainly produce
      pentalenic acid (1), together with neopentalenoketolactone (9). Disruption of the
      sav7469 gene encoding a cytochrome P450 (CYP105D7), members of which class are
      associated with the hydroxylation of many structurally different compounds,
      abolished the production of pentalenic acid (1). The sav7469-deletion mutant
      derived from SUKA11 carrying pKU462?ptl-clusterDeltaptlH accumulated 1
      deoxypentalenic acid (5), but not pentalenic acid (1). Reintroduction of an extra
      copy of the sav7469 gene to SUKA11 Deltasav7469 carrying pKU462?ptl
      clusterDeltaptlH restored the production of pentalenic acid (1). Recombinant
      CYP105D7 prepared from Escherichia coli catalyzed the oxidative conversion of 1
      deoxypentalenic acid (5) to pentalenic acid (1) in the presence of the electron
      transport partners, ferredoxin (Fdx) and Fdx reductase, both in vivo and in
      vitro. These results unambiguously demonstrate that CYP105D7 is responsible for
      the conversion of 1-deoxypentalenic acid (5) to pentalenic acid (1), a shunt
      product in the biosynthesis of the pentalenolactone family of metabolites.

PMID- 21081952
TI  - Substrate specificity of benzamide synthetase involved in 4-hydroxy-3
      nitrosobenzamide biosynthesis.
AB  - Glutamine-dependent amidotransferase (Gn-AT) catalyzes the transfer of the amido
      nitrogen of glutamine to an acceptor substrate to produce glutamate and an
      aminated product. Although most Gn-ATs are involved in biosyntheses of primary
      metabolites, some are important in the synthesis of secondary metabolites.
      Recently, a Gn-AT (NspN) was discovered in the biosynthetic pathway of 4-hydroxy
      3-nitorosobenzamide in Streptomyces murayamaensis. NspN converts 3-amino-4
      hydroxybenzoic acid (3,4-AHBA) to 3-amino-4-hydroxybenzamide. Here, we report the
      amino-acceptor substrate specificity of NspN. NspN could use several benzoic acid
      derivatives as amino-acceptor substrates to produce corresponding benzamides and
      catalyze the amidation of several carboxylate-type phenylpropanoids, such as p
      coumaric acid, cinnamic acid and caffeic acid. NspN showed the highest activity
      toward its natural substrate 3,4-AHBA among the substrates examined. NspN and
      related bacterial Gn-ATs may be useful in developing combinatorial biosynthetic
      strategies for benzamide derivatives, which could, in turn, be used as
      therapeutic agents for a variety of diseases.

PMID- 21081953
TI  - Glucopiericidin C: a cytotoxic piericidin glucoside antibiotic produced by a
      marine Streptomyces isolate.

PMID- 21081954
TI  - The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N
      units in ansamycin and mitomycin antibiotics: a review.
AB  - The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA),
      the precursor of ansamycin and other antibiotics is reviewed. In this
      biosynthesis, genes for kanosamine formation have been recruited from other
      genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated
      and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4
      phosphate, the substrate for the formation of aminoDAHP. This is converted via 5
      deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into
      AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two
      catalytic functions: As a homodimer, it catalyzes the last reaction in the
      pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the
      beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes
      the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as
      a useful tool in the genetic screening for new ansamycins and other AHBA-derived
      natural products.

PMID- 21081955
TI  - Improved precursor-directed biosynthesis in E. coli via directed evolution.
AB  - Erythromycin and related macrolide antibiotics are widely used polyketide natural
      products. We have evolved an engineered biosynthetic pathway in Escherichia coli
      that yields erythromycin analogs from simple synthetic precursors. Multiple
      rounds of mutagenesis and screening led to the identification of new mutant
      strains with improved efficiency for precursor-directed biosynthesis. Genetic and
      biochemical analysis suggested that the phenotypically relevant alterations in
      these mutant strains were localized exclusively to the host-vector system, and
      not to the polyketide synthase. We also demonstrate the utility of this improved
      system through engineered biosynthesis of a novel alkynyl erythromycin derivative
      with comparable antibacterial activity to its natural counterpart. In addition to
      reinforcing the power of directed evolution for engineering macrolide
      biosynthesis, our studies have identified a new lead substance for investigating
      structure-function relationships in the bacterial ribosome.

PMID- 21081956
TI  - Altered 13C glucose metabolism in the cortico-striato-thalamo-cortical loop in
      the MK-801 rat model of schizophrenia.
AB  - Using a modified MK-801 (dizocilpine) N-methyl-D-aspartic acid (NMDA) receptor
      hypofunction model for schizophrenia, we analyzed glycolysis, as well as
      glutamatergic, GABAergic, and monoaminergic neurotransmitter synthesis and
      degradation. Rats received an injection of MK-801 daily for 6 days and on day 6,
      they also received an injection of [1-(13)C]glucose. Extracts of frontal cortex
      (FCX), parietal and temporal cortex (PTCX), thalamus, striatum, nucleus accumbens
      (NAc), and hippocampus were analyzed using (13)C nuclear magnetic resonance
      spectroscopy, high-performance liquid chromatography, and gas chromatography-mass
      spectrometry. A pronounced reduction in glycolysis was found only in PTCX, in
      which (13)C labeling of glucose, lactate, and alanine was decreased. (13)C
      enrichment in lactate, however, was reduced in all areas investigated. The
      largest reductions in glutamate labeling were detected in FCX and PTCX, whereas
      in hippocampus, striatum, and Nac, (13)C labeling of glutamate was only slightly
      but significantly reduced. The thalamus was the only region with unaffected
      glutamate labeling. gamma-Aminobutyric acid (GABA) labeling was reduced in all
      areas, but most significantly in FCX. Glutamine and aspartate labeling was
      unchanged. Mitochondrial metabolites were also affected. Fumarate labeling was
      reduced in FCX and thalamus, whereas malate labeling was reduced in FCX, PTCX,
      striatum, and NAc. Dopamine turnover was decreased in FCX and thalamus, whereas
      that of serotonin was unchanged in all regions. In conclusion, neurotransmitter
      metabolism in the cortico-striato-thalamo-cortical loop is severely impaired in
      the MK-801 (dizocilpine) NMDA receptor hypofunction animal model for
      schizophrenia.

PMID- 21081958
TI  - Comparison of four nutritional screening tools to detect nutritional risk in
      hospitalized patients: a multicentre study.
AB  - BACKGROUND/OBJECTIVES: The prevalence of malnutrition in hospitals is high. No
      nutritional screening tool is considered the gold standard for identifying
      nutritional risk. The aims of this study were to evaluate nutritional risk in
      hospitalized patients using four nutritional screening tools. SUBJECTS/METHODS:
      Four nutritional screening tools were evaluated: nutritional risk screening (NRS
      2002), the malnutrition universal screening tool (MUST), the subjective global
      assessment (SGA) and the mini nutritional assessment (MNA). Patients were
      assessed within the first 36 h after hospital admission. Date of admission,
      diagnosis, complications and date of discharge were collected. To compare the
      tools, the results were reorganized into: patients at risk and patients with a
      good nutritional status. The statistical analysis included the chi(2)-test to
      assess differences between the tests and the kappa statistic to assess agreement
      between the tests. RESULTS: The study sample comprised 400 patients (159 women,
      241 men), mean age 67.3 (16.1) years. The prevalence of patients at nutritional
      risk with the NRS-2002, MUST, SGA and MNA was 34.5, 31.5, 35.3 and 58.5%,
      respectively. Statistically significant differences were observed between the
      four nutritional screening tools (P<0.001). The agreement between the tools was
      quite good except for the MNA (MNA-SGA kappa=0.491, NRS-2002-SGA kappa=0.620 and
      MUST-SGA kappa=0.635). Patients at nutritional risk developed more complications
      during admission and had an increased length of stay. CONCLUSIONS: The prevalence
      of nutritional risk in hospitalized patients was high with all the tools used.
      The best agreement between the tools was for NRS-2002 with SGA and MUST with SGA.
      At admission, NRS-2002 and MUST should be used to screen for nutritional status.

PMID- 21081957
TI  - Chronic hyperperfusion and angiogenesis follow subacute hypoperfusion in the
      thalamus of rats with focal cerebral ischemia.
AB  - Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined
      long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal
      cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling
      magnetic resonance imaging was decreased in the ipsilateral and contralateral
      thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred
      by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days
      and 3 months compared with its contralateral side. This contrasted with permanent
      hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by
      endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel
      branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only
      transient thalamic IgG extravasation was observed, indicating that the blood
      brain barrier was intact after day 2. Angiogenesis was preceded by transiently
      altered expression levels of cadherin family adhesion molecules, cadherin-7,
      protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after
      focal cerebral ischemia involved long-term hemodynamic changes and angiogenesis
      preceded by altered expression of vascular adhesion factors. Postischemic
      angiogenesis in the thalamus represents a novel type of remote plasticity, which
      may support removal of necrotic brain tissue and aid functional recovery.

PMID- 21081959
TI  - A non-hydrolyzed, fermented milk formula reduces digestive and respiratory events
      in infants at high risk of allergy.
AB  - BACKGROUND/OBJECTIVES: To determine the impact of a not hydrolyzed fermented
      infant formula containing heat-killed Bifidobacterium breve C50 and Streptococcus
      thermophilus 065 (HKBBST) on the incidence of allergy-like events during the
      first 2 years of life in children at high risk of atopy. SUBJECTS/METHODS: This
      multicenter, randomized, double-blind, controlled study included infants at high
      risk of atopy. Infants used HKBBST or a standard infant formula (SIF) since birth
      until 1 year of age, and were followed at 4, 12 and 24 months after birth. Skin
      prick tests (SPTs) for six foods and six aeroallergens were systematically
      performed and adverse events (AEs) were recorded. In case of potentially allergic
      AE (PAAE), allergy could be further tested by SPT, patch tests and quantification
      of specific IgEs. If cow's milk allergy (CMA) was suspected, an oral challenge
      could also be performed. RESULTS: The study included 129 children, 63 were
      randomized to SIF, 66 to HKBBST. The use of HKBBST milk did not alter the
      proportion of CMA but decreased the proportion of positive SPT to cow's milk (1.7
      vs 12.5%, P=0.03), and the incidence of digestive (39 vs 63%, P=0.01) and
      respiratory potentially allergic AEs (7 vs 21%, P=0.03) at 12 months, and that of
      respiratory PAAEs at 24 months (13 vs 35%, P=0.01). CONCLUSIONS: HKBBST decreased
      the incidence of PAAEs in children with family history of atopy, during the first
      months of life and after the formula was stopped. Oral tolerance to cow's milk in
      infants at high risk of atopy may therefore be improved using not hydrolyzed
      fermented formulae.

PMID- 21081960
TI  - Let's see how tmRNA rescues a stuck ribosome.
AB  - In the current issue, Weis et al (2010a) and Fu et al (2010) provide cryo
      electron microscopy snapshots of different states of the bacterial ribosome
      rescuing complex with tmRNA. This regulatory RNA molecule remarkably carries both
      tRNA- and mRNA-like elements that have to move through the ribosome machinery
      when it is stalled on an mRNA lacking a termination codon. The comparison of
      three intermediate states gives novel insights into the mechanism of tmRNA
      translocation and transient accommodation on the ribosome, and into trans
      translation-the template switching from a defective mRNA to the short coding
      region of the tmRNA, which allows rescuing the stuck ribosome.

PMID- 21081961
TI  - Membrane trafficking: On track for delivery.

PMID- 21081962
TI  - Oxidative stress: ATM bonds under stress.

PMID- 21081964
TI  - Peroxisomal protein import and ERAD: variations on a common theme.
AB  - Despite their distinct biological functions, there is a surprising similarity
      between the composition of the machinery that imports proteins into peroxisomes
      and the machinery that degrades endoplasmic reticulum (ER)-associated proteins.
      The basis of this similarity lies in the fact that both machineries make use of
      the same basic mechanistic principle: the tagging of a substrate by
      monoubiquitylation or polyubiquitylation and its subsequent recognition and ATP
      dependent removal from a membrane by ATPases of the ATPases associated with
      diverse cellular activities (AAA) family of proteins. We propose that the ER
      associated protein degradation (ERAD)-like removal of the peroxisomal import
      receptor is mechanically coupled to protein translocation into the organelle,
      giving rise to a new concept of export-driven import.

PMID- 21081965
TI  - Population structure and genetic differentiation associated with breeding history
      and selection in tomato (Solanum lycopersicum L.).
AB  - Tomato (Solanum lycopersicum L.) has undergone intensive selection during and
      following domestication. We investigated population structure and genetic
      differentiation within a collection of 70 tomato lines representing contemporary
      (processing and fresh-market) varieties, vintage varieties and landraces. The
      model-based Bayesian clustering software, STRUCTURE, was used to detect
      subpopulations. Six independent analyses were conducted using all marker data
      (173 markers) and five subsets of markers based on marker type (single-nucleotide
      polymorphisms, simple sequence repeats and insertion/deletions) and location
      (exon and intron sequences) within genes. All of these analyses consistently
      separated four groups predefined by market niche and age into distinct
      subpopulations. Furthermore, we detected at least two subpopulations within the
      processing varieties. These subpopulations correspond to historical patterns of
      breeding conducted for specific production environments. We found no
      subpopulation within fresh-market varieties, vintage varieties and landraces when
      using all marker data. High levels of admixture were shown in several varieties
      representing a transition in the demarcation between processing and fresh-market
      breeding. The genetic clustering detected by using the STRUCTURE software was
      confirmed by two statistics, pairwise F(st) (theta) and Nei's standard genetic
      distance. We also identified a total of 19 loci under positive selection between
      processing, fresh-market and vintage germplasm by using an F(st)-outlier method
      based on the deviation from the expected distribution of F(st) and
      heterozygosity. The markers and genome locations we identified are consistent
      with known patterns of selection and linkage to traits that differentiate the
      market classes. These results demonstrate how human selection through breeding
      has shaped genetic variation within cultivated tomato.

PMID- 21081963
TI  - The prion hypothesis: from biological anomaly to basic regulatory mechanism.
AB  - Prions are unusual proteinaceous infectious agents that are typically associated
      with a class of fatal degenerative diseases of the mammalian brain. However, the
      discovery of fungal prions, which are not associated with disease, suggests that
      we must now consider the effect of these factors on basic cellular physiology in
      a different light. Fungal prions are epigenetic determinants that can alter a
      range of cellular processes, including metabolism and gene expression pathways,
      and these changes can lead to a range of prion-associated phenotypes. The
      mechanistic similarities between prion propagation in mammals and fungi suggest
      that prions are not a biological anomaly but instead could be a newly appreciated
      and perhaps ubiquitous regulatory mechanism.

PMID- 21081966
TI  - Heritability and genetic correlation between the sexes in a songbird sexual
      ornament.
AB  - The genetic correlation between the sexes in the expression of secondary sex
      traits in wild vertebrate populations has attracted very few previous empirical
      efforts of field researchers. In southern European populations of pied
      flycatchers, a sexually selected male ornament is also expressed by a proportion
      of females. Additive genetic variances in ornament size and expression,
      transmission mechanisms (autosomal vs Z-linkage) and maternal effects are
      examined by looking at patterns of familial resemblance across three generations.
      Size of the secondary sex trait has a genetic basis common to both sexes, with
      estimated heritability being 0.5 under an autosomal model of inheritance.
      Significant additive genetic variance in males was also confirmed through a cross
      fostering experiment. Heritability analyses were only partially consistent with
      previous molecular genetics evidence, as only two out of the three predictions
      supported Z-linkage and lack of significant mother-daughter resemblance could be
      due to small sample sizes caused by limited female trait expression. Therefore,
      the evidence was mixed as to the contribution of the Z chromosome and autosomal
      genes to trait size. The threshold heritability of trait expression in females
      was lower, around 0.3, supporting autosomal-based trait expression in females.
      Environmental (birth date) and parental effects on ornament size mediated by the
      mother's condition after accounting for maternal and paternal genetic influences
      are also highlighted. The genetic correlation between the sexes did not differ
      from one, indicating that selection on the character on either sex entails a
      correlated response in the opposite sex.

PMID- 21081967
TI  - DNA polymorphism in recombining and non-recombining mating-type-specific loci of
      the smut fungus Microbotryum.
AB  - The population-genetic processes leading to the genetic degeneration of non
      recombining regions have mainly been studied in animal and plant sex chromosomes.
      Here, we report population genetic analysis of the processes in the non
      recombining mating-type-specific regions of the smut fungus Microbotryum
      violaceum. M. violaceum has A1 and A2 mating types, determined by mating-type
      specific 'sex chromosomes' that contain 1-2 Mb long non-recombining regions. If
      genetic degeneration were occurring, then one would expect reduced DNA
      polymorphism in the non-recombining regions of this fungus. The analysis of DNA
      diversity among 19 M. violaceum strains, collected across Europe from Silene
      latifolia flowers, revealed that (i) DNA polymorphism is relatively low in all 20
      studied loci (pi~0.15%), (ii) it is not significantly different between the two
      mating-type-specific chromosomes nor between the non-recombining and recombining
      regions, (iii) there is substantial population structure in M. violaceum
      populations, which resembles that of its host species, S. latifolia, and (iv)
      there is significant linkage disequilibrium, suggesting that widespread selfing
      in this species results in a reduction of the effective recombination rate across
      the genome. We hypothesise that selfing-related reduction of recombination across
      the M. violaceum genome negates the difference in the level of DNA polymorphism
      between the recombining and non-recombining regions, and may possibly lead to
      similar levels of genetic degeneration in the mating-type-specific regions of the
      non-recombining 'sex chromosomes' and elsewhere in the genome.

PMID- 21081968
TI  - Widespread introgression does not leak into allotopy in a broad sympatric zone.
AB  - Species that overlap over a large part of their range and habitat requirements
      are challenging for the study of speciation and hybridization. In this respect,
      the study of broadscale introgressive hybridization has raised recent interest.
      Here we studied hybridization between two closely related amphibians Lissotriton
      helveticus and Lissotriton vulgaris that reproduce over a wide sympatric zone. We
      used mitochondrial and microsatellite markers on 1272 individuals in 37 sites
      over Europe to detect hybrids at the individual-level and to analyse Hardy
      Weinberg and linkage disequilibria at the population-level. Morphological traits
      showed a strong bimodal distribution. Consistently, hybrid frequency was low
      (1.7%). We found asymmetric introgression with five times more hybrids in L.
      vulgaris than in L. helveticus, a pattern probably explained by an unequal
      effective population size in a study part wherein L. helveticus numerically
      predominates. Strikingly, significant levels of introgression were detected in
      73% of sites shared by both species. Our study showed that introgression is
      widespread but remains confined to the sites where the two species reproduce at
      the same time. This pattern may explain why these species remain genetically
      distinct over a broad sympatric zone.

PMID- 21081969
TI  - Discriminative accuracy of genomic profiling comparing multiplicative and
      additive risk models.
AB  - Genetic prediction of common diseases is based on testing multiple genetic
      variants with weak effect sizes. Standard logistic regression and Cox
      Proportional Hazard models that assess the combined effect of multiple variants
      on disease risk assume multiplicative joint effects of the variants, but this
      assumption may not be correct. The risk model chosen may affect the predictive
      accuracy of genomic profiling. We investigated the discriminative accuracy of
      genomic profiling by comparing additive and multiplicative risk models. We
      examined genomic profiles of 40 variants with genotype frequencies varying from
      0.1 to 0.4 and relative risks varying from 1.1 to 1.5 in separate scenarios
      assuming a disease risk of 10%. The discriminative accuracy was evaluated by the
      area under the receiver operating characteristic curve. Predicted risks were more
      extreme at the lower and higher risks for the multiplicative risk model compared
      with the additive model. The discriminative accuracy was consistently higher for
      multiplicative risk models than for additive risk models. The differences in
      discriminative accuracy were negligible when the effect sizes were small (<1.2),
      but were substantial when risk genotypes were common or when they had stronger
      effects. Unraveling the exact mode of biological interaction is important when
      effect sizes of genetic variants are moderate at the least, to prevent the
      incorrect estimation of risks.

PMID- 21081971
TI  - Does the HSD17B10 gene escape from X-inactivation?

PMID- 21081970
TI  - LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy
      founder population.
AB  - Primary congenital glaucoma (PCG) is a genetically heterogeneous autosomal
      recessive disorder, which is an important cause of blindness in childhood. The
      first known gene, CYP1B1, accounts for a variable proportion of cases in most
      populations. A second gene, LTBP2, was recently reported in association with a
      syndrome, in which glaucoma is secondary to lens dislocation. We report on the
      molecular and clinical profile of 34 families diagnosed as PCG, all originating
      from the Roma/Gypsy founder population. Comprehensive sequencing analysis
      revealed a level of heterogeneity unusual for this population, with five CYP1B1
      and one ancestral LTBP2 mutation accounting for ~70% of patients (25 out of 37)
      and the remainder still unexplained. Homozygosity for the founder LTBP2 p.R299X
      mutation resulted in a more severe clinical phenotype and poorer outcome despite
      a markedly higher number of surgical interventions. The genetically homogeneous
      group of p.R299X homozygotes showed variable phenotypes (presumably also
      underlying pathogenetic mechanisms), wherein PCG proper with primary dysgenesis
      of the trabecular meshwork, and Marfan syndrome-like zonular disease with ectopia
      lentis and later onset secondary glaucoma are two extremes. The spectrum
      manifestations may occur in different combinations and have a different evolution
      even within the same sibship or a single patient. Preliminary observations on
      compounds with mutations in both CYP1B1-LTBP2 suggest that the observed
      combinations are of no clinical significance and digenic inheritance is unlikely.
      We provide a population genetics perspective to explain the allelic
      heterogeneity, comparing the history and geographic distribution of the two major
      founder mutations--p.R299X/LTBP2 and p.E387K/CYP1B1.

PMID- 21081973
TI  - High-speed terahertz time-domain spectroscopy based on electronically controlled
      optical sampling.
AB  - We demonstrate high-speed terahertz (THz) time-domain spectroscopy based on
      electronically controlled optical sampling (ECOPS). The ECOPS system utilizes two
      synchronized Ti:sapphire femtosecond lasers with a 100 MHz repetition frequency.
      The time delay between the two laser pulses is demonstrated to be rapidly swept
      at a scan rate of 1 kHz on a time delay window of 77 ps by using an external
      offset voltage applied to a locking electronics. It is shown that a THz pulse can
      be exactly measured by ECOPS, as is done by asynchronous optical sampling
      (ASOPS), and the measurement time is shortened by a factor of 50 by using ECOPS
      compared with ASOPS in the case of employing 100 MHz repetition-rate lasers.

PMID- 21081972
TI  - Implications of the exposome for exposure science.
AB  - During the 1920s, the forerunners of exposure science collaborated with health
      professionals to investigate the causes of occupational diseases. With the birth
      of U.S. regulatory agencies in the 1970s, interest in the environmental origins
      of human diseases waned, and exposure scientists focused instead upon levels of
      selected contaminants in air and water. In fact, toxic chemicals enter the body
      not only from exogenous sources (air, water, diet, drugs, and radiation) but also
      from endogenous processes, including inflammation, lipid peroxidation, oxidative
      stress, existing diseases, infections, and gut flora. Thus, even though current
      evidence suggests that non-genetic factors contribute about 90% of the risks of
      chronic diseases, we have not explored the vast majority of human exposures that
      might initiate disease processes. The concept of the exposome, representing the
      totality of exposures received by a person during life, encompasses all sources
      of toxicants and, therefore, offers scientists an agnostic approach for
      investigating the environmental causes of chronic diseases. In this context, it
      is appropriate to regard the "environment" as the body's internal chemical
      environment and to define "exposures" as levels of biologically active chemicals
      in this internal environment. To explore the exposome, it makes sense to employ a
      top-down approach based upon biomonitoring (e.g. blood sampling) rather than a
      bottom-up approach that samples air, water, food, and so on. Because sources and
      levels of exposure change over time, exposomes can be constructed by analyzing
      toxicants in blood specimens obtained during critical stages of life. Initial
      investigations could use archived blood from prospective cohort studies to
      measure important classes of toxic chemicals, notably, reactive electrophiles,
      metals, metabolic products, hormone-like substances, and persistent organic
      compounds. The exposome offers health scientists an avenue for integrating
      research that is currently fractured along lines related to particular diseases
      and risk factors, and can thereby promote discovery of the key exposures
      responsible for chronic diseases. By embracing the exposome as its operational
      paradigm, exposure science can play a major role in discovering and mitigating
      these exposures.

PMID- 21081974
TI  - Fast frequency-guided sequential demodulation of a single fringe pattern.
AB  - Fast frequency-guided sequential demodulation (FFSD) for demodulating a single
      closed-fringe pattern is proposed as an improvement of frequency-guided
      sequential demodulation (FSD). Instead of using optimization to estimate the
      local frequencies for determining the sign of the phase, the FFSD estimates the
      local frequencies by directly calculating the gradient of the obtained phase with
      an undetermined sign. This improvement considerably reduces the computational
      complexity of the FSD and leads to a faster and simpler method. Simulated and
      experimental fringe patterns are used to test the proposed method and show that
      the demodulation speed of FFSD is about 150 times faster than that of the FSD,
      while the robustness and accuracy remain almost the same.

PMID- 21081976
TI  - Elimination of the chirp of optical pulses through cascaded nonlinearities in
      periodically poled lithium niobate waveguides.
AB  - We propose and demonstrate a novel method for the elimination of arbitrary
      frequency chirp from short optical pulses. The technique is based on the
      combination of two cascaded second-order nonlinearities in two individual
      periodically poled lithium niobate waveguides. The proposed scheme operates
      independently of the spectral phase characteristics of the input pulse, producing
      a near-transform-limited output.

PMID- 21081975
TI  - Multiplex coherent anti-Stokes Raman microspectroscopy with tailored Stokes
      spectrum.
AB  - We combined the ultrabroadband supercontinuum of a photonic crystal fiber with a
      pulse shaper, resulting in a highly flexible light source for multiplex coherent
      anti-Stokes Raman microscopy. Implemented as the Stokes pulse, it provides
      tailored selection of the relevant Raman transitions, resulting in a reduced
      photon load and partial suppression of the nonresonant background. This
      experiment exploits the advantages of multiplex excitation with the increased
      acquisition speed of single-channel detection. The molecule-specific Stokes
      pulses are demonstrated for chemical mapping of a polymer blend.

PMID- 21081977
TI  - Performance evaluation of adaptive meshing algorithms for fluorescence diffuse
      optical tomography using experimental data.
AB  - Fluorescence diffuse optical tomography (FDOT) is a computationally demanding
      imaging problem. The discretizations of FDOT forward and inverse problems pose a
      trade-off between the accuracy and the computational efficiency of the image
      reconstruction. To address this trade-off, we analyzed the effect of
      discretization on the accuracy of FDOT imaging and proposed novel adaptive
      meshing algorithms for FDOT in a series of studies. In this Letter, we apply
      these new adaptive meshing algorithms to FDOT imaging using real data from a
      phantom experiment to demonstrate the practical advantages of our algorithms in
      FDOT image reconstruction.

PMID- 21081978
TI  - Bragg scattering in a positive beta4 fiber.
AB  - The phase-matching curves for the four-wave mixing effect of Bragg scattering in
      two fibers with opposite sign beta(4) dispersion coefficients have been measured
      experimentally. The measured phase-matching curves are in good agreement with
      theoretical expectations, and their dependence on several key parameters has been
      determined.

PMID- 21081979
TI  - Direct measurement of the instantaneous linewidth of rapidly wavelength-swept
      lasers.
AB  - The instantaneous linewidth of rapidly wavelength-swept laser sources as used for
      optical coherence tomography (OCT) is of crucial interest for a deeper
      understanding of physical effects involved in their operation. Swept lasers for
      OCT, typically sweeping over ~15 THz in ~10 MUs, have linewidths of several
      gigahertz. The high optical-frequency sweep speed makes it impossible to measure
      the instantaneous spectrum with standard methods. Hence, up to now, experimental
      access to the instantaneous linewidth was rather indirect by the inverse Fourier
      transform of the coherence decay. In this Letter, we present a method by fast
      synchronous time gating and extraction of a "snapshot" of the instantaneous
      spectrum with an electro-optic modulator, which can subsequently be measured with
      an optical spectrum analyzer. This new method is analyzed in detail, and
      systematic artifacts, such as sideband generation due to the modulation and
      residual wavelength uncertainty due to the sweeping operation, are quantified.
      The method is checked for consistency with results from the common, more indirect
      measurement via coherence properties.

PMID- 21081980
TI  - Coherence and anticoherence resonance in high-concentration erbium-doped fiber
      laser.
AB  - We report an experimental study of low-frequency (~10 kHz) self-pulsing of the
      output intensity in a high-concentration erbium-doped fiber laser. We suggest
      that the fast intensity fluctuations caused by multimode and polarization
      instabilities play the role of an external noise source, leading to low-frequency
      auto-oscillations through a coherence resonance scenario.

PMID- 21081981
TI  - Analysis of a diffusion-model-based approach for efficient quantification of
      superficial tissue properties.
AB  - Previously, we reported using a diffusing probe in conjunction with a two-layer
      diffusion model for accurately recovering the optical properties of superficial
      volumes. However, the two-layer diffusion equation is computationally less
      efficient than a standard diffusion equation (SDE) by 3 orders of magnitude. In
      this Letter, we present a new approach extended from the diffusing probe geometry
      that enables the use of a diffusion model that has efficiency comparable to an
      SDE. Our Monte Carlo simulation results indicate that this new approach is not
      only very accurate but also sensitive to the presence of 0.5 mm(3)
      inhomogeneities and could be used for monitoring the early progression of skin
      melanoma.

PMID- 21081982
TI  - Continuous-wave single-frequency 532 nm laser source emitting 130 W into the
      fundamental transversal mode.
AB  - The nonlinear effect of second-harmonic generation is an efficient way to realize
      high-power green laser sources. But when scaling up the harmonic power, many
      setups reported in the literature have been limited by conversion efficiency
      degradation or the fundamental laser power. Here we report on the generation of
      134 W of cw laser light at a wavelength of 532 nm from a fundamental power of 149
      W by second-harmonic generation in an external optical resonator comprising a
      lithium triborate crystal. The external conversion efficiency was 90%. The
      harmonic light consisted of a single spectral line. At least 97% of it was
      emitted into the fundamental transversal mode.

PMID- 21081983
TI  - Optical deflection tomography with the phase-shifting schlieren.
AB  - We present a new optical deflection tomography method that takes advantage of the
      phase-shifting schlieren. The reconstruction algorithm is based on filtered
      backprojection. The instrument is well adapted for three-dimensional imaging of
      spatially sparse objects exhibiting large refractive index variations. It
      achieves a 35 MUm resolution with a 3 mm depth of field. Its performance is
      illustrated with a bundle of fibers immersed in a matching index solution.

PMID- 21081984
TI  - Infrared dipole antenna enhanced by surface phonon polaritons.
AB  - In this Letter, we propose a gold dipole antenna formed on a SiC substrate to
      achieve a strong concentration of mid-IR radiation based on a synergistic
      integration of the IR dipole antenna and the resonance excitation of a surface
      phonon polariton. Numerical simulation based on the finite-difference time-domain
      technique shows that the intensity enhancement can be greater than 10(7) times at
      the mid-IR spectral region. The influence of the geometric parameters (i.e.,
      antenna length, gap dimension, antenna thickness, and antenna width) on the
      antenna field enhancement is also studied. The strong intensity enhancement can
      find important applications in highly sensitive mid-IR photodetectors and in
      molecular detection and identification by surface-enhanced IR absorption
      spectroscopy techniques.

PMID- 21081986
TI  - Characterization of solid complex multiphase systems based on oscillatory photon
      correlation spectroscopy.
AB  - The particle loading and dispersion profiles are two significant properties
      directly affecting the engineering properties and performance characteristics of
      polymer nanocomposites. Current measurement techniques are often destructive,
      require special sample preparation, are limited to small, unrepresentative sample
      size, and/or cannot discriminate between the two aforementioned parameters. This
      Letter demonstrates the application of photon correlation spectroscopy on
      mechanically oscillated solids; experimental results show that this technique can
      discriminate between different grades of such materials.

PMID- 21081985
TI  - Utility of biodegradable plasmonic nanoclusters in photoacoustic imaging.
AB  - Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast
      agents because of their resonant optical absorption properties in the visible and
      near-IR regions. However, the nanoparticles could accumulate and result in long
      term toxicity in vivo, because they are generally not biodegradable. Recently,
      biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold
      nanoparticles and biodegradable polymer stabilizer, were introduced. In this
      Letter, we demonstrate the feasibility of biodegradable nanoclusters as a
      photoacoustic contrast agent. We performed photoacoustic and ultrasound imaging
      of a tissue-mimicking phantom with inclusions containing nanoclusters at various
      concentrations. The results indicate that the biodegradable gold nanoclusters can
      be used as effective contrast agents in photoacoustic imaging.

PMID- 21081987
TI  - Highly efficient, high-power, broadly tunable, cryogenically cooled and diode
      pumped Yb:CaF2.
AB  - We present a high-power diode-pumped Yb:CaF(2) laser operating at cryogenic
      temperature (77 K). A laser output power of 97 W at 1034 nm was extracted for a
      pump power of 245 W. The corresponding global extraction efficiency (versus
      absorbed pump power) is 65%. The laser small signal gain was found to be equal to
      3.1. The laser wavelength could be tuned between 990 and 1052 nm with peaks that
      correspond well to the structure of the gain cross-section spectra registered at
      low temperature.

PMID- 21081988
TI  - Parametric self-trapping in the presence of randomized quasi phase matching.
AB  - We report on experimental evidence of parametric spatial solitons in a quadratic
      crystal with randomized periodic ferroelectric poling. Two-color self-focusing
      via quadratic cascading overcomes the diffractive nature of both fundamental and
      frequency-doubled beams.

PMID- 21081989
TI  - Focusing of light beyond the diffraction limit of half the wavelength.
AB  - The diffraction limit sets the smallest achievable linewidth at half the
      wavelength. With a subwavelength plasmonic lens allowing one to reduce the
      diffraction via an asymmetry and to generate and squeeze the wave functions, an
      incident light is focused by the aperture to a single line with its width smaller
      than the limited value in the intermediate zone. The focused fields are capable
      of propagating in free space. This light focusing process, besides being of
      academic interest, is expected to open up a wide range of application
      possibilities.

PMID- 21081990
TI  - Multispectral microbolometers for the midinfrared.
AB  - The spectral responsivity and the dynamic behavior of microbolometers with an
      integrated absorbing metamaterial are investigated. Wavelength tailoring and
      tuning in different microbolometers are achieved by varying the lateral extension
      of the absorber elements. Maximum sensitivity is tuned between 2.9 and 7.7 MUm,
      with peak absorptions reaching up to 88%. The presence of a continuous metallic
      shielding layer affects heat conduction and leads to faster thermal response
      times.

PMID- 21081991
TI  - In situ characterization of an optical cavity using atomic light shift.
AB  - We report the precise characterization of the optical potential obtained by
      injecting a distributed-feedback erbium-doped fiber laser at 1560 nm to the
      transverse modes of a folded optical cavity. The optical potential was mapped in
      situ using cold rubidium atoms, whose potential energy was spectrally resolved
      thanks to the strong differential light shift induced by the 1560 nm laser on the
      two levels of the probe transition. The optical potential obtained in the cavity
      is suitable for trapping rubidium atoms and eventually to achieve all-optical
      Bose-Einstein condensation directly in the resonator.

PMID- 21081992
TI  - Color changes in stochastic light fields propagating in non-Kolmogorov
      turbulence.
AB  - The dependence of spectral shifts and switches in optical stochastic beams
      propagating through nonclassic turbulent medium on the slope of the power
      spectrum of fluctuations in the refractive index is revealed.

PMID- 21081993
TI  - Plasmonic tomography of optical vortices.
AB  - We present a method for analyzing the wavefront of optical vortices that does not
      involve interferometry but rather uses surface plasmon polaritons (SPPs). We
      employ a subwavelength slit in a gold film to cut slices from an optical vortex
      beam and measure the diffraction of the generated SPPs by scattering them off a
      second slit. By moving the slits across the vortex beam, we create a tomogram,
      from which we can determine the vortex charge of the incident beam at a glance.
      We present results for vortex beams of integer- and half-integer-vortex charge.

PMID- 21081994
TI  - Efficient frequency conversion induced by quantum constructive interference.
AB  - We demonstrate in experiment an efficient cw four-wave mixing scheme with maximal
      intensity conversion efficiency up to 73% in a double-Lambda system of hot
      rubidium atoms. Relevant theoretical analysis shows that this high conversion
      efficiency benefits greatly from the constructive interference between two four
      wave mixing channels, characterized by two different space-dependent phases.

PMID- 21081995
TI  - Actively mode-locked fiber ring laser by intermodal acousto-optic modulation.
AB  - We report an actively mode-locked fiber ring laser. A simple and low-insertion
      loss acousto-optic modulator driven by standing flexural waves, which couples
      core-to-cladding modes in a standard single-mode optical fiber, is used as an
      active mechanism for mode locking. Among the remarkable features of the
      modulator, we mention its high modulation depth (72%), broad bandwidth (187 GHz),
      easy tunability in the optical wavelength, and low insertion losses (0.7 dB). The
      narrowest optical pulses obtained were of 95 ps time width, 21 mW peak power,
      repetition rate of 4.758 MHz, and 110 mW of pump power.

PMID- 21081996
TI  - Compact static Fourier transform imaging spectropolarimeter based on channeled
      polarimetry.
AB  - The theoretical operation and experimental demonstration of a Fourier transform
      imaging spectropolarimeter for real time measurement of the polarization state of
      light are presented. The spectropolarimeter uses a Wollaston prism as a
      birefringent interferometer and two high-order retarders to incorporate channeled
      polarimetry. Compared with previous instruments, the most significant advantage
      of the described model is that the complete wavelength-dependent polarization is
      acquired simultaneously along a one-dimensional spatial image by a single
      snapshot. Also, we show that, in this configuration, we can benefit from the
      advantages of the model: it is compact and robust, and the birefringent
      interferometer has a high throughput.

PMID- 21081997
TI  - Natural shaping of the cylindrically polarized beams.
AB  - We have experimentally and theoretically shown that the circularly polarized beam
      bearing a singly charged optical vortex propagating through a uniaxial crystal
      can be split after focusing into the radially and azimuthally polarized beams in
      the vicinity of the focal area provided that the polarization handedness and the
      vortex topological charge have opposite signs.

PMID- 21081998
TI  - Multiple Cerenkov second-harmonic waves in a two-dimensional nonlinear photonic
      structure.
AB  - We report simultaneous generation of multiple conical second-harmonic waves in a
      two-dimensional nonlinear photonic structure when illuminated by two overlapping
      noncollinear fundamental beams. We show that this phenomenon is caused by the
      nonlinear Cerenkov radiation emitted due to the interaction of photons from each
      constituent fundamental beam as well as the virtual one propagating along the
      bisector of the two beams. In addition, by studying the asymmetric geometry of
      the interaction, we uniquely verify the effects of reciprocal vectors on the
      Cerenkov-type second-harmonic generation in nonlinear photonic structures.

PMID- 21082000
TI  - High-resolution two-dimensional image upconversion of incoherent light.
AB  - We consider a technique for high-resolution image upconversion of thermal light.
      Experimentally, we demonstrate cw upconversion with a resolution of more than 200
      * 1000 pixels of thermally illuminated objects. This is the first demonstration
      (to our knowledge) of high-resolution cw image upconversion. The upconversion
      method promises an alternative route to high-quantum-efficiency all-optical
      imaging in the mid-IR wavelength region and beyond using standard CCD cameras. A
      particular advantage of CCD cameras compared to state-of-the-art thermal cameras
      is the possibility to tailor and tune the spectral response leading to functional
      spectral imaging.

PMID- 21081999
TI  - Epitaxial Nd-doped alpha-(Al(1-x)Ga(x))2O3 films on sapphire for solid-state
      waveguide lasers.
AB  - Single-crystal aluminum-gallium oxide films have been grown by molecular beam
      epitaxy in the corundum phase. Films of the (Al(1-x)Ga(x))(2)O(3) alloys doped
      with neodymium have favorable properties for solid-state waveguide lasers,
      including a high-thermal-conductivity sapphire substrate and a dominant emission
      peak in the 1090-1096 nm wavelength range. The peak position is linearly
      correlated to the unit cell volume, which is dependent on film composition and
      stress. Varying the Ga-Al alloy composition during growth will enable the
      fabrication of graded-index layers for tunable lasing wavelengths and low
      scattering losses at the interfaces.

PMID- 21082001
TI  - High-performance fiber-laser-based terahertz spectrometer.
AB  - We have developed a rapid scanning terahertz (THz) spectrometer based on a
      synchronized two-fiber-laser system. When the system is set to the asynchronous
      optical sampling mode, THz spectra extending to 3 THz can be acquired within 1
      MUs at a signal-to-noise ratio of the electric field of better than 20. Signal
      averaging results in a dynamic range of more than 60 dB, and frequency components
      of more than 4 THz can be detected. When the lasers are set to the same
      repetition rate, electronically controlled optical sampling at a rate of 2.5 kHz
      is demonstrated, making the system versatile for different spectroscopic
      applications. Finally, we compare the THz emission spectra of a photoconductive
      switch that is pumped at 780 nm and a nonlinear DAST crystal excited at 1550 nm.
      We find that the spectral range of the spectrometer is significantly enhanced at
      higher frequencies, while the dynamic range remains constant.

PMID- 21082002
TI  - Enhanced twinkling in left-handed media.
AB  - A slab of left-handed material (LHM) with refractive index -1 forms a perfect
      lens that retains subwavelength information about a source or object. Such lenses
      are highly susceptible to perturbations affecting their performance. It is shown
      that illuminating a roughened interface between air and an LHM produces a regime
      for enhanced focusing of light close to the boundary. This generates caustics
      that are brighter, fluctuate more, and cause Gaussian speckle at distances closer
      to the interface than in right-handed matter. These effects present fresh
      challenges for perfecting the perfect lens.

PMID- 21082003
TI  - All-fiber design of hybrid Er-doped laser/Yb-doped amplifier system for high
      power ultrashort pulse generation.
AB  - We propose a design of an all-fiber laser system that combines the most advanced
      Er:fiber laser in the telecommunication range and an efficient Yb-doped amplifier
      for generation of high-power ultrashort pulses. The system is based on nonlinear
      wavelength conversion of 1.56 MUm ultrashort Er:fiber laser pulses to the 1 MUm
      range in a short pigtail of dispersion-shifted silica fiber with subsequent
      amplification in the Yb-doped fiber amplifier. Pulses with a duration as short as
      85 fs and averaged power of 200 mW are demonstrated.

PMID- 21082004
TI  - Molecular ruler based on concurrent measurements of enhanced Raman scattering and
      fluorescence.
AB  - We report a way to assess the separation between a molecule and a metal surface
      on account of both Raman scattering and fluorescence intensities measured
      simultaneously. This approach has no need for an accurate quantity of molecules
      and bears 1 nm resolution. Its distance sensitivity is experimentally
      demonstrated in the case of dye molecules lying on a gold surface with a polymer
      spacer layer in between and is compared with theoretical prediction.

PMID- 21082005
TI  - Channeled spectropolarimetry using a coherent white-light continuum.
AB  - We carry out polarization measurements using a coherent white-light continuum as
      a light source for channeled spectropolarimetry. The white-light continuum, whose
      spectrum ranges from the UV to the IR region, is generated in Kr gas by a
      terawatt femtosecond laser system. The complete set of Stokes parameters from 450
      700 nm are reconstructed from one spectral measurement. Also, the effectiveness
      of channeled spectropolarimetry using a coherent white-light continuum is
      experimentally demonstrated with a highly attenuating sample whose transmittance
      is as low as 10(-6).

PMID- 21082006
TI  - Loss measurement of plasmonic modes in planar metal-insulator-metal waveguides by
      an attenuated total reflection method.
AB  - We report experimental excitation and characterization of surface plasmon modes
      in planar metal-insulator-metal (MIM) waveguides. Our approach is based on
      determining the width of the reflection angular spectrum in the attenuated total
      reflection (ATR) configuration. Owing to its transverse character, the ATR
      configuration provides a more straightforward and simpler way to determine the
      loss of plasmonic modes in MIM structures, compared to using tapered end couplers
      with multiple waveguide samples or scanning near-field optical microscopy. In
      this Letter, two waveguide structures with Au claddings and 50/200 nm SiO(2)
      cores are investigated. The propagation lengths measured at lambda = 1.55 MUm are
      5.7 and 18 MUm, respectively, in agreement with the theoretical predictions.

PMID- 21082007
TI  - Optical image encryption based on diffractive imaging.
AB  - In this Letter, we propose a method for optical image encryption based on
      diffractive imaging. An optical multiple random phase mask encoding system is
      applied, and one of the phase-only masks is selected and laterally translated
      along a preset direction during the encryption process. For image decryption, a
      phase retrieval algorithm is proposed to extract a high-quality plaintext. The
      feasibility and effectiveness of the proposed method are demonstrated by
      numerical results. The proposed method can provide a new strategy instead of
      conventional interference methods, and it may open up a new research perspective
      for optical image encryption.

PMID- 21082008
TI  - Extreme ultraviolet interferometry of warm dense matter in laser plasmas.
AB  - We demonstrate that interferometric probing with extreme ultraviolet (EUV) laser
      light enables determination of the degree of ionization of the "warm dense
      matter" produced between the critical and ablation surfaces of laser plasmas.
      Interferometry has been utilized to measure both transmission and phase
      information for an EUV laser beam at the photon energy of 58.5 eV, probing
      longitudinally through laser-irradiated plastic (parylene-N) targets (thickness
      350 nm) irradiated by a 300 ps duration pulse of wavelength 438 nm and peak
      irradiance 10(12) W cm(-2). The transmission of the EUV probe beam provides a
      measure of the rate of target ablation, as ablated plasma becomes close to
      transparent when the photon energy is less than the ionization energy of the
      predominant ion species. We show that refractive indices eta below the solid
      parylene N (eta(solid) = 0.946) and expected plasma values are produced in the
      warm dense plasma created by laser irradiation due to bound-free absorption in
      C(+).

PMID- 21082009
TI  - Surface plasmon interference on the surface of an aluminum-covered fiber core
      array for solgel fabrication of submicrometer gratings.
AB  - An interesting method to fabricate submicrometer gratings (SMGs) utilizing the
      interference of surface plasmon waves (SPWs) is presented. The stationary wave
      field off the aluminum (Al) layer surface of an Al-covered UV fiber core, formed
      by the interference of the induced SPWs, has been employed as a submicrometer
      photolithography tool to inscribe SMGs on the surface of a self-processing hybrid
      HfO(2)/SiO(2) solgel film. Using atomic force microscopy, the period of the
      fabricated SMGs was measured as 105 nm. The intensity distribution of the
      stationary wave field was measured by a near-field scanning optical microscope
      and anastomosed with theoretical values calculated by using FDTD simulations.

PMID- 21082010
TI  - Optical switch using a deformable liquid droplet.
AB  - An optical switch based on a deformable liquid droplet is demonstrated. The
      device consists of a clear liquid droplet surrounded by a black liquid. In the
      voltage-off state, the incident light is absorbed by the black liquid. As the
      voltage increases, the dielectric force reshapes the droplet by uplifting its
      dome. As the dome touches the top substrate, a clear channel is opened, allowing
      the incident light to pass through. Once the voltage is removed, the deformed
      droplet relaxes back to its original shape and the channel is closed. Devices
      based on such an operation mechanism have potential applications in light
      shutters, variable optical attenuators, adaptive irises, and displays.

PMID- 21082011
TI  - Fabrication and characterization of on-chip optical nonlinear chalcogenide
      nanofiber devices.
AB  - Chalcogenide (As(2)S(3)) nanofibers as narrow as 200 nm in diameter are drawn by
      the fiber pulling method, are successfully embedded in SU8 polymer, and form on
      chip waveguides and high-Q microknot resonators (Q = 3.9 * 10(4)) with smooth
      cleaved end faces. Resonance tuning of resonators is realized by localized laser
      irradiation. Strong supercontinuum generation with a bandwidth of 500 nm is
      achieved in a 7-cm-long on-chip chalcogenide waveguide. Our result provides a
      method for the development of compact, high-optical-quality, and robust photonic
      devices.

PMID- 21082012
TI  - High-repetition-rate near-infrared noncollinear ultrabroadband optical parametric
      amplification in KTiOPO4.
AB  - We report efficient noncollinear optical parametric amplification (NOPA) of
      ultrabroadband near-IR pulses tunable in the 1.1-1.5 MUm range at a repetition
      rate of 250 kHz. Improved generation of smooth near-IR continua (extending over
      ~1.0-1.6 MUm) at 250 kHz was achieved by weakly focusing ~20% of the 1 W driving
      laser beam into a sapphire plate with longer focal length lenses than previously
      reported. Using bulk potassium-titanyl phosphate (KTiOPO(4)) pumped at 800 nm,
      powers as high as 11 mW (14% pump conversion efficiency) and signal pulse
      durations as short as 23 fs were obtained after a single white-light seeded NOPA
      stage.

PMID- 21082013
TI  - Disposable and compact integrated plasmonic sensor using a long-period grating.
AB  - This Letter theoretically proposes and investigates an integrated plasmonic
      sensor that is based on a grating-assisted coupling between a surface plasmon
      polariton (SPP) and a dielectric waveguide (DW) mode. It consists of a glass
      slide with a gold film for the propagation of an SPP and a separate DW with a
      long-period grating. For sensing, the two parts are temporarily combined. After
      sensing, the former is replaceable, and so the sensor has disposability. The
      design procedure and analysis method for the sensor are explained. The designed
      sensor is shown to be very compact. Its characteristics of sensing a change of
      the refractive index of liquid are analyzed and discussed.

PMID- 21082015
TI  - Intensity correlation properties of high-order optical vortices passing through a
      rotating ground-glass plate.
AB  - We study the intensity correlation properties of optical vortices passing through
      a rotating ground-glass (RGG) plate and compare them with those of the TEM(00)
      mode of an He-Ne laser beam passed through the same RGG. We have observed that
      the intensity correlation curves for optical vortices decrease much faster than
      the corresponding curve for a TEM(00) mode of the He-Ne laser. The rate of decay
      of the correlation increases with the increase of order of the vortices. Our
      experimentally observed results are supported by exact analytical results.

PMID- 21082014
TI  - Microlens array recording of localized retinal responses.
AB  - We designed a rapid functional imager for the parallel recording of localized
      intrinsic optical signals (IOSs). This imager used a microlens array (MLA)-based
      illuminator to deliver visible stimulus light and near-infrared (NIR) recording
      light simultaneously. The parfocal configuration of the stimulus and recording
      light illumination enabled confocal recording of the stimulus-evoked IOSs.
      Because the MLA stimulation/recording spots were widely separated on the retina,
      and only the photoreceptors within the MLA stimulation/recording spots were
      stimulated, the potential IOS cross talk effect among neighboring retinal areas
      was minimized. Our experiments revealed robust IOS activities tightly correlated
      with localized retinal responses.

PMID- 21082016
TI  - Transparency in Bragg scattering and phase conjugation.
AB  - Reflectionless transmission of light waves with unitary transmittance is shown to
      occur in a certain class of gain-grating structures and phase-conjugation mirrors
      in the unstable (above-threshold) regime. Such structures are synthesized by
      means of the Darboux method developed in the context of supersymmetric
      relativistic quantum mechanics. Transparency is associated to superluminal pulse
      transmission.

PMID- 21082017
TI  - On the concept of "tractor beams".
AB  - We demonstrate the existence of a class of optical beams where the
      nonconservative forces can be locally oriented in a direction opposite to the
      propagation wave vector. Objects placed in the vicinity of these locations will
      move toward the source of light. The behavior of these negative forces is
      discussed for the particular case of nondiffracting rotating scale-invariant
      vector electromagnetic waves.

PMID- 21082018
TI  - Vector Brillouin optical time-domain analyzer for high-order acoustic modes.
AB  - Thanks to a double-frequency phase modulation scheme, we report a vector
      Brillouin optical time-domain analyzer (BOTDA). This BOTDA has a high immunity
      level to noise, and it features a phase spectrogram capability. It is well suited
      for complex situations involving several acoustic resonances, such as high-order
      longitudinal modes. It has notably been used to characterize a dispersion-shifted
      fiber, allowing us to report spectrograms with multiple acoustic resonances. A
      very high 57 dB dynamic range is also reported for 100-ns-long pulses
      simultaneously with a 16 cm numerical resolution.

PMID- 21082019
TI  - Modulation-free frequency stabilization of external-cavity diode laser based on a
      phase-difference biased Sagnac interferometer.
AB  - We propose a modulation-free technique for frequency stabilization of an external
      cavity diode laser (ECDL) by using a phase-difference biased Sagnac
      interferometer to produce dispersion spectroscopic error signals. A half-wave
      plate and a total internal reflection prism are inserted into the loop to provide
      a phase-difference bias between the clockwise and counterclockwise beams with
      perpendicular polarizations, instead of the previous method with misaligned
      optical paths. In the experiments, the frequency of the Littman-Metcalf
      configuration ECDL is locked at the transition of the Rb atomic vapor, and the
      frequency fluctuation is suppressed from 8 to less than 0.5 MHz peak to peak. It
      is shown that this scheme is simple, robust, low cost, and it shows promise for
      use in a variety of related applications.

PMID- 21082020
TI  - Single-shot, high-dynamic-range measurement of sub-15 fs pulses by self
      referenced spectral interferometry.
AB  - We explore theoretically and numerically the temporal contrast limitation of a
      self-referenced spectral interferometry measurement. An experimental confirmation
      is given by characterization and fine compression of hollow-core fiber generated
      sub-15 fs pulses, yielding an accurately measured coherent contrast of 50 dB on a
      +/-400 fs time range.

PMID- 21082021
TI  - GABAergic synapse properties may explain genetic variation in hippocampal network
      oscillations in mice.
AB  - Cognitive ability and the properties of brain oscillation are highly heritable in
      humans. Genetic variation underlying oscillatory activity might give rise to
      differences in cognition and behavior. How genetic diversity translates into
      altered properties of oscillations and synchronization of neuronal activity is
      unknown. To address this issue, we investigated cellular and synaptic mechanisms
      of hippocampal fast network oscillations in eight genetically distinct inbred
      mouse strains. The frequency of carbachol-induced oscillations differed
      substantially between mouse strains. Since GABAergic inhibition sets oscillation
      frequency, we studied the properties of inhibitory synaptic inputs (IPSCs)
      received by CA3 and CA1 pyramidal cells of three mouse strains that showed the
      highest, lowest and intermediate frequencies of oscillations. In CA3 pyramidal
      cells, the frequency of rhythmic IPSC input showed the same strain differences as
      the frequency of field oscillations. Furthermore, IPSC decay times in both CA1
      and CA3 pyramidal cells were faster in mouse strains with higher oscillation
      frequencies than in mouse strains with lower oscillation frequency, suggesting
      that differences in GABA(A)-receptor subunit composition exist between these
      strains. Indeed, gene expression of GABA(A)-receptor beta2 (Gabrb2) and beta3
      (Gabrb2) subunits was higher in mouse strains with faster decay kinetics compared
      with mouse strains with slower decay kinetics. Hippocampal pyramidal neurons in
      mouse strains with higher oscillation frequencies and faster decay kinetics fired
      action potential at higher frequencies. These data indicate that differences in
      genetic background may result in different GABA(A)-receptor subunit expression,
      which affects the rhythm of pyramidal neuron firing and fast network activity
      through GABA synapse kinetics.

PMID- 21082022
TI  - Genome-wide association study of blood pressure extremes identifies variant near
      UMOD associated with hypertension.
AB  - Hypertension is a heritable and major contributor to the global burden of
      disease. The sum of rare and common genetic variants robustly identified so far
      explain only 1%-2% of the population variation in BP and hypertension. This
      suggests the existence of more undiscovered common variants. We conducted a
      genome-wide association study in 1,621 hypertensive cases and 1,699 controls and
      follow-up validation analyses in 19,845 cases and 16,541 controls using an
      extreme case-control design. We identified a locus on chromosome 16 in the 5'
      region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 * 10-11). The
      minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87
      [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and
      each copy of the G allele is associated with a 7.7% reduction in risk of CVD
      events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95%
      CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated
      glomerular filtration rate (eGFR) measurements, we show that rs13333226 is
      independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83
      0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In
      clinical functional studies, we also consistently show the minor G allele is
      associated with lower urinary uromodulin excretion. The exclusive expression of
      uromodulin in the thick portion of the ascending limb of Henle suggests a
      putative role of this variant in hypertension through an effect on sodium
      homeostasis. The newly discovered UMOD locus for hypertension has the potential
      to give new insights into the role of uromodulin in BP regulation and to identify
      novel drugable targets for reducing cardiovascular risk.

PMID- 21082023
TI  - A draft of the human septin interactome.
AB  - BACKGROUND: Septins belong to the GTPase superclass of proteins and have been
      functionally implicated in cytokinesis and the maintenance of cellular
      morphology. They are found in all eukaryotes, except in plants. In mammals, 14
      septins have been described that can be divided into four groups. It has been
      shown that mammalian septins can engage in homo- and heterooligomeric assemblies,
      in the form of filaments, which have as a basic unit a hetero-trimeric core. In
      addition, it has been speculated that the septin filaments may serve as scaffolds
      for the recruitment of additional proteins. METHODOLOGY/PRINCIPAL FINDINGS: Here,
      we performed yeast two-hybrid screens with human septins 1-10, which include
      representatives of all four septin groups. Among the interactors detected, we
      found predominantly other septins, confirming the tendency of septins to engage
      in the formation of homo- and heteropolymeric filaments.
      CONCLUSIONS/SIGNIFICANCE: If we take as reference the reported arrangement of the
      septins 2, 6 and 7 within the heterofilament, (7-6-2-2-6-7), we note that the
      majority of the observed interactions respect the "group rule", i.e. members of
      the same group (e.g. 6, 8, 10 and 11) can replace each other in the specific
      position along the heterofilament. Septins of the SEPT6 group preferentially
      interacted with septins of the SEPT2 group (p<0.001), SEPT3 group (p<0.001) and
      SEPT7 group (p<0.001). SEPT2 type septins preferentially interacted with septins
      of the SEPT6 group (p<0.001) aside from being the only septin group which
      interacted with members of its own group. Finally, septins of the SEPT3 group
      interacted preferentially with septins of the SEPT7 group (p<0.001). Furthermore,
      we found non-septin interactors which can be functionally attributed to a variety
      of different cellular activities, including: ubiquitin/sumoylation cycles,
      microtubular transport and motor activities, cell division and the cell cycle,
      cell motility, protein phosphorylation/signaling, endocytosis, and apoptosis.

PMID- 21082024
TI  - A comprehensive ex vivo functional analysis of human NKT cells reveals production
      of MIP1-alpha and MIP1-beta, a lack of IL-17, and a Th1-bias in males.
AB  - NKT cells contribute to the modulation of immune responses and are believed to be
      important in the pathogenesis of autoimmune and infectious diseases, as well as
      cancer. Variations in the composite NKT cytokine response may determine
      individual disease susceptibility or severity. Due to low frequencies in
      peripheral blood, knowledge of the breadth of ex vivo human NKT cell functions
      has been limited. To bridge this gap, we studied highly purified NKT cells from
      PBMC of healthy donors and assessed the production of 27 effector functions using
      sensitive Elispot and multiplex bead assays. We found the ex vivo human NKT cell
      response is predominantly comprised of the chemokines MIP1-alpha, and MIP1-beta
      as well as the Th1 cytokines IFN-gamma and TNF-alpha. Although lower in
      magnitude, there was also significant production of IL-2, IL-4, and perforin
      after mitogen stimulation. Surprisingly, little/no IL-5, IL-6, IL-10, or IL-13
      was detected, and no subjects' NKT cells produced IL-17. Comparison of the NKT
      functional profiles between age-matched male and female subjects revealed similar
      IL-4 responses, but higher frequencies of cells producing IFN-gamma and MIP1
      alpha, from males. There were no gender differences in the circulating NKT subset
      distribution. These findings implicate chemokines as a major mechanism by which
      NKT cells control responses in humans. In addition, the panoply of Th2 and Th17
      cytokine secretion by NKT cells from healthy donors may not be as pronounced as
      previously believed. NKT cells may therefore contribute to the gender bias found
      in many diseases.

PMID- 21082025
TI  - Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of
      adjuvant and number of component alleles on the breadth of response.
AB  - There is increasing interest in multi-allele vaccines to overcome strain
      specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1
      (AMA1). These have been shown to induce broad inhibitory antibodies in vitro and
      formed the basis for the design of three Diversity-Covering (DiCo) proteins with
      similar immunological effects. The antibodies produced are to epitopes that are
      shared between vaccine alleles and theoretically, increasing the number of
      component AMA1 alleles is expected to broaden the antibody response. A plateau
      effect could however impose a limit on the number of alleles needed to achieve
      the broadest specificity. Moreover, production cost and the vaccine formulation
      process would limit the number of component alleles. In this paper, we compare
      rabbit antibody responses elicited with multi-allele vaccines incorporating seven
      (three DiCos and four natural AMA1 alleles) and three (DiCo mix) antigens for
      gains in broadened specificity. We also investigate the effect of three adjuvant
      platforms on antigen specificity and antibody functionality. Our data confirms a
      broadened response after immunisation with DiCo mix in all three adjuvants.
      Higher antibody titres were elicited with either CoVaccine HTTM or Montanide ISA
      51, resulting in similar in vitro inhibition (65-82%) of five out of six culture
      adapted P. falciparum strains. The antigen binding specificities of elicited
      antibodies were also similar and independent of the adjuvant used or the number
      of vaccine component alleles. Thus neither the four extra antigens nor adjuvant
      had any observable benefits with respect to specificity broadening, although
      adjuvant choice influenced the absolute antibody levels and thus the extent of
      parasite inhibition. Our data confirms the feasibility and potential of multi
      allele PfAMA1 formulations, and highlights the need for adjuvants with improved
      antibody potentiation properties for AMA1-based vaccines.

PMID- 21082026
TI  - Expression and membrane topology of Anopheles gambiae odorant receptors in
      lepidopteran insect cells.
AB  - A lepidopteran insect cell-based expression system has been employed to express
      three Anopheles gambiae odorant receptors (ORs), OR1 and OR2, which respond to
      components of human sweat, and OR7, the ortholog of Drosophila's OR83b, the
      heteromerization partner of all functional ORs in that system. With the aid of
      epitope tagging and specific antibodies, efficient expression of all ORs was
      demonstrated and intrinsic properties of the proteins were revealed. Moreover,
      analysis of the orientation of OR1 and OR2 on the cellular plasma membrane
      through the use of a novel 'topology screen' assay and FACS analysis demonstrates
      that, as was recently reported for the ORs in Drosophila melanogaster, mosquito
      ORs also have a topology different than their mammalian counterparts with their N
      terminal ends located in the cytoplasm and their C-terminal ends facing outside
      the cell. These results set the stage for the production of mosquito ORs in
      quantities that should permit their detailed biochemical and structural
      characterization and the exploration of their functional properties.

PMID- 21082027
TI  - Daily timed sexual interaction induces moderate anticipatory activity in mice.
AB  - Anticipation of resource availability is a vital skill yet it is poorly
      understood in terms of neuronal circuitry. Rodents display robust anticipatory
      activity in the several hours preceding timed daily access to food when access is
      limited to a short temporal duration. We tested whether this anticipatory
      behavior could be generalized to timed daily social interaction by examining if
      singly housed male mice could anticipate either a daily novel female or a
      familiar female. We observed that anticipatory activity was moderate under both
      conditions, although both a novel female partner and sexual experience are
      moderate contributing factors to increasing anticipatory activity. In contrast,
      restricted access to running wheels did not produce any anticipatory activity,
      suggesting that an increase in activity during the scheduled access time was not
      sufficient to induce anticipation. To tease apart social versus sexual
      interaction, we tested the effect of exposing singly housed female mice to a
      familiar companion female mouse daily. The female mice did not show anticipatory
      activity for restricted female access, despite a large amount of social
      interaction, suggesting that daily timed social interaction between mice of the
      same gender is insufficient to induce anticipatory activity. Our study
      demonstrates that male mice will show anticipatory activity, albeit
      inconsistently, for a daily timed sexual encounter.

PMID- 21082028
TI  - Evidence for enhanced mutualism hypothesis: Solidago canadensis plants from
      regular soils perform better.
AB  - The important roles of plant-soil microbe interactions have been documented in
      exotic plant invasion, but we know very little about how soil mutualists enhance
      this process (i.e. enhanced mutualism hypothesis). To test this hypothesis we
      conducted two greenhouse experiments with Solidago canadensis (hereafter
      Solidago), an invasive forb from North America, and Stipa bungeana (hereafter
      Stipa), a native Chinese grass. In a germination experiment, we found soil
      microbes from the rhizospheres of Solidago and Stipa exhibited much stronger
      facilitative effects on emergence of Solidago than that of Stipa. In a growth and
      competition experiment, we found that soil microbes strongly facilitated Solidago
      to outgrow Stipa, and greatly increased the competitive effects of Solidago on
      Stipa but decreased the competitive effects of Stipa on Solidago. These findings
      from two experiments suggest that in situ soil microbes enhance the recruitment
      potential of Solidago and its ability to outcompete native plants, thereby
      providing strong evidence for the enhanced mutualism hypothesis. On the other
      hand, to some extent this outperformance of Solidago in the presence of soil
      microbes seems to be unbeneficial to control its rapid expansion, particularly in
      some ranges where this enhanced mutualism dominates over other mechanisms.

PMID- 21082029
TI  - Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the
      GPER agonist G-1 in female mRen2.Lewis rats.
AB  - INTRODUCTION: The G protein-coupled estrogen receptor (GPER) is expressed in
      various tissues including the heart. Since the mRen2.Lewis strain exhibits salt
      dependent hypertension and early diastolic dysfunction, we assessed the effects
      of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH)
      on cardiac function and structure. METHODS: Intact female mRen2.Lewis rats were
      fed a normal salt (0.5% sodium; NS) diet or a high salt (4% sodium; HS) diet for
      10 weeks beginning at 5 weeks of age. RESULTS: Prolonged intake of HS in
      mRen2.Lewis females resulted in significantly increased blood pressure, mildly
      reduced systolic function, and left ventricular (LV) diastolic compliance (as
      signified by a reduced E deceleration time and E deceleration slope), increased
      relative wall thickness, myocyte size, and mid-myocardial interstitial and
      perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte
      hypertrophy, with nominal effects on blood pressure, LV systolic function, LV
      compliance and cardiac fibrosis in the HS group. G-1 treatment significantly
      increased LV lusitropy [early mitral annular descent (e')] independent of
      prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05) as
      determined by tissue Doppler. CONCLUSION: Activation of GPER improved myocardial
      relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte
      hypertrophy and wall thickness in those rats fed a high salt diet. Moreover,
      these advantageous effects of the GPER agonist on ventricular lusitropy and
      remodeling do not appear to be associated with overt changes in blood pressure.

PMID- 21082030
TI  - Localization and androgen regulation of metastasis-associated protein 1 in mouse
      epididymis.
AB  - BACKGROUND: Metastasis-associated protein 1 (MTA1), the founding member of the
      MTA family of genes, can modulate transcription by influencing the status of
      chromatin remodeling. Despite its strong correlation with the metastatic
      potential of cancer cells, MTA1 can also regulate crucial cellular pathways by
      modifying the acetylation status. We have previously reported the presence of
      MTA1/MTA1 in human and mouse testes, providing the evidence for its involvement
      in the regulation of testicular function during murine spermatogenesis. The
      objective of present study was to further assess the localization of MTA1 in
      mouse epididymis on both transcriptional and translational level, and then to
      explore whether MTA1 expression is regulated by androgens and postnatal
      epididymal development. METHODOLOGY/PRINCIPAL FINDINGS: Mice were deprived of
      circulating androgen by bilaterally castration and were then supplemented with
      exogenous testosterone propionate for one week. MTA1 was immunolocalized in the
      epithelium of the entire epididymis with the maximal expression in the nuclei of
      principal cells and of clear cells in proximal region. Its expression decreased
      gradually after castration, whereas testosterone treatment could restore the
      expression, indicating that the expression of this gene is dependent on androgen.
      During postnatal development, the protein expression in the epididymis began to
      appear from day 7 to day 14, increased dramatically from postnatal day 28, and
      peaked at adulthood onwards, coinciding with both the well differentiated status
      of epididymis and the mature levels of circulating androgens. This region- and
      cell-specific pattern was also conservative in normal human epididymis.
      CONCLUSIONS: Our data suggest that the expression of MTA1 protein could be
      regulated by androgen pathway and its expression level is closely associated with
      the postnatal development of the epididymis, giving rise to the possibility that
      this gene plays a potential role in sperm maturation and fertility.

PMID- 21082031
TI  - Disturbed expression of splicing factors in renal cancer affects alternative
      splicing of apoptosis regulators, oncogenes, and tumor suppressors.
AB  - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of
      renal cancer. One of the processes disturbed in this cancer type is alternative
      splicing, although phenomena underlying these disturbances remain unknown.
      Alternative splicing consists of selective removal of introns and joining of
      residual exons of the primary transcript, to produce mRNA molecules of different
      sequence. Splicing aberrations may lead to tumoral transformation due to
      synthesis of impaired splice variants with oncogenic potential. In this paper we
      hypothesized that disturbed alternative splicing in ccRCC may result from
      improper expression of splicing factors, mediators of splicing reactions.
      METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we
      analyzed expression of seven splicing factors belonging to SR proteins family
      (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP
      A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control
      ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in
      carcinogenesis and partially regulated by analyzed splicing factors: RON,
      CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the
      mRNA expression of splicing factors was disturbed in tumors when compared to
      paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The
      correlation coefficients between expression levels of specific splicing factors
      were increased in tumor samples. Moreover, alternative splicing of five analyzed
      genes was also disturbed in ccRCC samples and splicing pattern of two of them,
      Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We
      conclude that disturbed expression of splicing factors in ccRCC may possibly lead
      to impaired alternative splicing of genes regulating tumor growth and this way
      contribute to the process of carcinogenesis.

PMID- 21082032
TI  - Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis
      infected macrophages.
AB  - BACKGROUND: Studies on the role of neutrophils in Leishmania infection were
      mainly performed with L. (L) major, whereas less information is available for L.
      (L) amazonensis. Previous results from our laboratory showed a large infiltrate
      of neutrophils in the site of infection in a mouse strain resistant to L. (L.)
      amazonensis (C3H/HePas). In contrast, the susceptible strain (BALB/c) displayed a
      predominance of macrophages harboring a high number of amastigotes and very few
      neutrophils. These findings led us to investigate the interaction of inflammatory
      neutrophils with L. (L.) amazonensis-infected macrophages in vitro.
      METHODOLOGY/PRINCIPAL FINDINGS: Mouse peritoneal macrophages infected with L.
      (L.) amazonensis were co-cultured with inflammatory neutrophils, and after four
      days, the infection was quantified microscopically. Data are representative of
      three experiments with similar results. The main findings were 1) intracellular
      parasites were efficiently destroyed in the co-cultures; 2) the leishmanicidal
      effect was similar when cells were obtained from mouse strains resistant
      (C3H/HePas) or susceptible (BALB/c) to L. (L.) amazonensis; 3) parasite
      destruction did not require contact between infected macrophages and neutrophils;
      4) tumor necrosis factor alpha (TNF-alpha), neutrophil elastase and platelet
      activating factor (PAF) were involved with the leishmanicidal activity, and 5)
      destruction of the parasites did not depend on generation of oxygen or nitrogen
      radicals, indicating that parasite clearance did not involve the classical
      pathway of macrophage activation by TNF-alpha, as reported for other Leishmania
      species. CONCLUSIONS/SIGNIFICANCE: The present results provide evidence that
      neutrophils in concert with macrophages play a previously unrecognized
      leishmanicidal effect on L. (L.) amazonensis. We believe these findings may help
      to understand the mechanisms involved in innate immunity in cutaneous infection
      by this Leishmania species.

PMID- 21082038
TI  - Blasted cell line names.
AB  - BACKGROUND: While trying to integrate multiple data sets collected by different
      researchers, we noticed that the sample names were frequently entered
      inconsistently. Most of the variations appeared to involve punctuation, white
      space, or their absence, at the juncture between alphabetic and numeric portions
      of the cell line name. RESULTS: Reasoning that the variant names could be
      described in terms of mutations or deletions of character strings, we implemented
      a simple version of the Needleman-Wunsch global sequence alignment algorithm and
      applied it to the cell line names. All correct matches were found by this
      procedure. Incorrect matches only occured when a cell line was present in one
      data set but not in the other. The raw match scores tended to be substantially
      worse for the incorrect matches. CONCLUSIONS: A simple application of the
      Needleman-Wunsch global sequence alignment algorithm provides a useful first pass
      at matching sample names from different data sets.

PMID- 21082039
TI  - Estimating Shared Copy Number Aberrations for Array CGH Data: The Linear-Median
      Method.
AB  - MOTIVATION: Existing methods for estimating copy number variations in array
      comparative genomic hybridization (aCGH) data are limited to estimations of the
      gain/loss of chromosome regions for single sample analysis. We propose the linear
      median method for estimating shared copy numbers in DNA sequences across multiple
      samples, demonstrate its operating characteristics through simulations and
      applications to real cancer data, and compare it to two existing methods.
      RESULTS: Our proposed linear-median method has the power to estimate common
      changes that appear at isolated single probe positions or very short regions.
      Such changes are hard to detect by current methods. This new method shows a
      higher rate of true positives and a lower rate of false positives. The linear
      median method is non-parametric and hence is more robust in estimating copy
      number. Additionally the linear-median method is easily computable for practical
      aCGH data sets compared to other copy number estimation methods.

PMID- 21082037
TI  - Breast cancer biomarker discovery in the functional genomic age: a systematic
      review of 42 gene expression signatures.
AB  - In this review we provide a systematic analysis of transcriptomic signatures
      derived from 42 breast cancer gene expression studies, in an effort to identify
      the most relevant breast cancer biomarkers using a meta-analysis method. Meta
      data revealed a set of 117 genes that were the most commonly affected ranging
      from 12% to 36% of overlap among breast cancer gene expression studies. Data
      mining analysis of transcripts and protein-protein interactions of these commonly
      modulated genes indicate three functional modules significantly affected among
      signatures, one module related with the response to steroid hormone stimulus, and
      two modules related to the cell cycle. Analysis of a publicly available gene
      expression data showed that the obtained meta-signature is capable of predicting
      overall survival (P < 0.0001) and relapse-free survival (P < 0.0001) in patients
      with early-stage breast carcinomas. In addition, the identified meta-signature
      improves breast cancer patient stratification independently of traditional
      prognostic factors in a multivariate Cox proportional-hazards analysis.

PMID- 21082040
TI  - Cross-platform Comparison of Two Pancreatic Cancer Phenotypes.
AB  - Model-based approaches for combining gene expression data from multiple high
      throughput platforms can be sensitive to technological artifacts when the number
      of samples in each platform is small. This paper proposes simple tools for
      quantifying concordance in a small study of pancreatic cancer cells lines with an
      emphasis on visualizations that uncover intra- and inter-platform variation.
      Using this approach, we identify several transcripts from the integrative
      analysis whose over-or under-expression in pancreatic cancer cell lines was
      validated by qPCR.

PMID- 21082041
TI  - Compensation crisis related to the onsite adequacy evaluation during FNA
      procedures-Urgent proactive input from cytopathology community is critical to
      establish appropriate reimbursement for CPT code 88172 (or its new counterpart if
      introduced in the future).
AB  - The confusion centered around appropriate use of the CPT billing code 88172 is
      addressed in the commentary from the Economic and Government Affairs Committee of
      the American Society of Cytopathology (ASC) who have written a timely commentary
      in this issue of Cytojournal, "Adequate Reimbursement is Crucial to Support Cost
      Effective Rapid Onsite Cytopathology Evaluations". Currently, lack of
      standardized use within and between pathology departments is stirring unhealthy
      practices of denying reimbursements for this critical and legitimate
      cytopathology service. This editorial discusses the important concerns raised in
      this commentary and recommends immediate corrective action. (See also Al-Abbadi
      MA, et al. Adequate reimbursement is crucial to support cost-effective rapid on
      site cytopathology evaluations. CytoJournal 2010;7:22).

PMID- 21082042
TI  - Genetic and epigenetic alterations after hybridization and genome doubling.
AB  - Hybridization and polyploidization are now recognized as major phenomena in the
      evolution of plants, promoting genetic diversity, adaptive radiation and
      speciation. Modern molecular techniques have recently provided evidence that
      allopolyploidy can induce several types of genetic and epigenetic events that are
      of critical importance for the evolutionary success of hybrids: (1) chromosomal
      rearrangements within one or both parental genomes contribute toward proper
      meiotic pairing and isolation of the hybrid from its progenitors; (2)
      demethylation and activation of dormant transposable elements may trigger
      insertional mutagenesis and changes in local patterns of gene expression,
      facilitating rapid genomic reorganisation; (3) rapid and reproducible loss of low
      copy DNA sequence appears to result in further differentiation of homoeologous
      chromosomes; and (4) organ-specific up- or down-regulation of one of the
      duplicated genes, resulting in unequal expression or silencing one copy. All
      these alterations also have the potential, while stabilizing allopolyploid
      genomes, to produce novel expression patterns and new phenotypes, which together
      with increased heterozygosity and gene redundancy might confer on hybrids an
      elevated evolutionary potential, with effects at scales ranging from molecular to
      ecological. Although important advances have been made in understanding genomic
      responses to allopolyploidization, further insights are still expected to be
      gained in the near future, such as the direction and nature of the diploidization
      process, functional relevance of gene expression alterations, molecular
      mechanisms that result in adaptation to different ecologies/habitats, and
      ecological and evolutionary implications of recurrent polyploidization.

PMID- 21082044
TI  - Comparative analysis of three different cervical lateral mass screw fixation
      techniques by complications and bicortical purchase : cadaveric study.
AB  - OBJECTIVE: The purpose of this study is to compare the incidence of possible
      complications of cervical lateral screw fixation and the achievements of
      bicortical purchase using the Roy-Camille, Magerl and the modified methods.
      METHODS: Six fresh-frozen cervical spine segments were harvested. The Roy-Camille
      technique was applied to C3 and C4, and the Magerl technique was applied to C5,
      C6, and C7 of one side of each cadaver. The modified technique was applied to the
      other side of each cadaver. The nerve root injury, violation of the facet joint,
      vertebral artery injury, and the bicortication were examined at each screwing
      level. RESULTS: No vertebral artery injury was observed in any of the three
      methods. One nerve root injury was observed in each cervical spine segment using
      the Roy-Camille method (8.3%), the Magerl method (5.6%), and the modified method
      (3.3%). Facet joint injuries were observed in two cervical spinal segments using
      the Roy-Camille method (16.7%) and three with the Magerl method (16.7%), while
      five facet joint violations occurred when using the modified method (16.7%).
      Bicortical purchases were achieved on ten cervical spinal segments with the Roy
      Camille method (83.3%) and Magerl method (55.6%), while twenty bicortical
      purchases were achieved in the modified method (66.7%). CONCLUSION: The
      advantages of the modified method are that it is performed by using given
      anatomical structures and that the complication rate is as low as those of other
      known methods. This modified method can be performed easily and safely without
      fluoroscopic assistance for the treatment of many cervical diseases.

PMID- 21082043
TI  - Integrative functional genomics analysis of sustained polyploidy phenotypes in
      breast cancer cells identifies an oncogenic profile for GINS2.
AB  - Aneuploidy is among the most obvious differences between normal and cancer cells.
      However, mechanisms contributing to development and maintenance of aneuploid cell
      growth are diverse and incompletely understood. Functional genomics analyses have
      shown that aneuploidy in cancer cells is correlated with diffuse gene expression
      signatures and aneuploidy can arise by a variety of mechanisms, including
      cytokinesis failures, DNA endoreplication, and possibly through polyploid
      intermediate states. To identify molecular processes contributing to development
      of aneuploidy, we used a cell spot microarray technique to identify genes
      inducing polyploidy and/or allowing maintenance of polyploid cell growth in
      breast cancer cells. Of 5760 human genes screened, 177 were found to induce
      severe DNA content alterations on prolonged transient silencing. Association with
      response to DNA damage stimulus and DNA repair was found to be the most enriched
      cellular processes among the candidate genes. Functional validation analysis of
      these genes highlighted GINS2 as the highest ranking candidate inducing
      polyploidy, accumulation of endogenous DNA damage, and impairing cell
      proliferation on inhibition. The cell growth inhibition and induction of
      polyploidy by suppression of GINS2 was verified in a panel of breast cancer cell
      lines. Bioinformatic analysis of published gene expression and DNA copy number
      studies of clinical breast tumors suggested GINS2 to be associated with the
      aggressive characteristics of a subgroup of breast cancers in vivo. In addition,
      nuclear GINS2 protein levels distinguished actively proliferating cancer cells
      suggesting potential use of GINS2 staining as a biomarker of cell proliferation
      as well as a potential therapeutic target.

PMID- 21082045
TI  - The avoidance of microsurgical complications in the extradural anterior
      clinoidectomy to paraclinoid aneurysms.
AB  - OBJECTIVE: Paraclinoid segment internal carotid artery (ICA) aneurysms have
      historically been a technical challenge for neurovascular surgeons. The
      development of microsurgical approach, advances in surgical techniques, and
      endovascular procedures have improved the outcome for paraclinoid aneurysms.
      However, many authors have reported high complication rates from microsurgical
      treatments. Therefore, the present study reviews the microsurgical complications
      of the extradural anterior clinoidectomy for treating paraclinoid aneurysms and
      investigates the prevention and management of observed complications. METHODS:
      Between January 2004 and April 2008, 22 patients with 24 paraclinoid aneurysms
      underwent microsurgical direct clipping by a cerebrovascular team at a regional
      neurosurgical center. Microsurgery was performed via an ipsilateral pterional
      approach with extradural anterior clinoidectomy. We retrospectively reviewed
      patients' medical charts, office records, radiographic studies, and operative
      records. RESULTS: IN OUR SERIES, THE CLINICAL OUTCOMES AFTER AN IPSILATERAL
      PTERIONAL APPROACH WITH EXTRADURAL ANTERIOR CLINOIDECTOMY FOR PARACLINOID
      ANEURYSMS WERE EXCELLENT OR GOOD (GLASGOWS OUTCOME SCALE : GOS 5 or 4) in 87.5%
      of cases. The microsurgical complications related directly to the extradural
      anterior clinoidectomy included transient cranial nerve palsy (6), cerebrospinal
      fluid leak (1), worsened change in vision (1), unplanned ICA occlusion (1), and
      epidural hematoma (1). Only one of the complications resulted in permanent
      morbidity (4.2%), and none resulted in death. CONCLUSION: Although surgical
      complications are still reported to occur more frequently for the treatment of
      paraclinoid aneurysms, the permanent morbidity and mortality resulting from a
      extradural anterior clinoidectomy in our series were lower than previously
      reported. Precise anatomical knowledge combined with several microsurgical
      tactics can help to achieve good outcomes with minimal complications.

PMID- 21082047
TI  - Clinical outcome of cranial neuropathy in patients with pituitary apoplexy.
AB  - OBJECTIVE: Pituitary apoplexy (PA) is described as a clinical syndrome
      characterized by sudden headache, vomiting, visual impairment, and meningismus
      caused by rapid enlargement of a pituitary adenoma. We retrospectively analyzed
      the clinical presentation and surgical outcome in PA presenting with cranial
      neuropathy. METHODS: Twelve cases (3.3%) of PA were retrospectively reviewed
      among 359 patients diagnosed with pituitary adenoma. The study included 6 males
      and 6 females. Mean age of patients was 49.0 years, with a range of 16 to 74
      years. Follow-up duration ranged from 3 to 20 months, with an average of 12
      months. All patients were submitted to surgery, using the transsphenoidal
      approach (TSA). RESULTS: Symptoms included abrupt headache (11/12), decreased
      visual acuity (12/12), visual field defect (11/12), and cranial nerve palsy of
      the third (5/12) and sixth (2/12). Mean height of the mass was 29.0 mm (range 15
      46). Duration between the ictus and operation ranged from 1 to 15 days (mean
      7.0). The symptom duration before operation and the recovery period of cranial
      neuropathy correlated significantly (p = 0.0286). TSA resulted in improvement of
      decreased visual acuity in 91.6%, visual field defect in 54.5%, and cranial
      neuropathy in 100% at 3 months after surgery. CONCLUSION: PA is a rare event,
      complicating 3.3% in our series. Even in blindness following pituitary apoplexy
      cases, improvement of cranial neuropathy is possible if adequate management is
      initiated in time. Surgical decompression must be considered as soon as possible
      in cases with severe visual impairment or cranial neuropathy.

PMID- 21082046
TI  - Endovascular Treatment of Wide-Necked Intracranial Aneurysms Using Balloon
      Assisted Technique with HyperForm Balloon.
AB  - OBJECTIVE: To assess the feasibility, safety, and effectiveness of the balloon
      assisted technique with HyperForm balloon in the endovascular treatment of wide
      necked intracranial aneurysms. METHODS: A total of 34 patients with 34 wide
      necked intracranial aneurysms were treated with endovascular coil embolization
      using balloon-assisted technique with Hyperform balloon. Twenty-nine aneurysms
      (85.3%) were located in the anterior circulation. The group of patients was
      comprised of 16 men and 18 women, aged 33 to 72 years (mean : 60.6 years). The
      size of aneurysms was in the range of 2.0 to 22.0 mm (mean 5.5 mm) and one of
      neck was 2.0 to 11.9 mm (mean 3.8 mm). The dome to neck ratio was ranged from
      0.83 to 1.43 (1.15). Sixteen patients were treated for unruptured aneurysms and
      the remaining 18 presented with a subarachnoid hemorrhage. RESULTS: In the 34
      aneurysms treated by the remodeling technique with HyperForm balloon, immediate
      angiographic results consisted of total occlusion in 31 cases (91.2%) and partial
      occlusion in three cases (8.8%). There were five procedure-related complications
      (14.7%), including two coil protrusions and three thromboembolisms; Except one
      patient, all were successfully resolved without permanent neurologic deficit. No
      new bleeding occurred during the follow-up. Twenty patients (59%) underwent
      angiographic follow-up from 2 to 33 months (mean 9.2 months) after treatment.
      Focal recanalization with coil compaction of the neck portion was observed in 5
      cases (25%). Only one case showed major recanalization and underwent stent
      assisted coil embolization. CONCLUSION: The balloon-assisted technique with
      Hyperform balloon is a feasible, safe, and effective endovascular treatment of
      wide-necked cerebral aneurysms.

PMID- 21082048
TI  - Minimally invasive transforaminal lumbar interbody fusion using a single
      interbody cage and a tubular retraction system : technical tips, and
      perioperative, radiologic and clinical outcomes.
AB  - OBJECTIVE: A minimally invasive transforaminal lumbar interbody fusion (MIS TLIF)
      has recently been introduced. However, MIS TLIF is a technically challenging
      procedure. The authors performed retrospective analysis about MIS TLIF using a
      single interbody cage. METHODS: Twenty-eight consecutive patients were treated by
      MIS TLIF. Of these 28 patients, 20 patients were included in this retrospective
      study. Perioperative, clinical, and radiologic outcomes were assessed. Clinical
      outcomes were assessed using Oswestry Disability Index (ODI) and Visual Analogue
      Scores (VAS). Fusion rates and cross-sections of operated spinal canals were
      assessed by CT. RESULTS: Twelve patients underwent MIS TLIF at one segment and 8
      patients at two segments (L3/4: 4, L4/5: 17, L5/S1: 7). Operation time for a
      single segment was 131.7 min and for two segment was 201.4 min, and corresponding
      blood losses were 208.3 mL and 481.2 mL, respectively. ODI and VAS scores were
      significantly improved at 6 months postop (ODI from 30.32 to 15. 54, VAS from
      7.80 to 2.20, p = 0.001). Twenty-two segments (78.6%) achieved grade I fusion, 4
      segments (14.3%) achieved grade II, 2 segments (7.1%) achieved grade III and 0
      segments achieved grade IV at 12 months. Postoperatively at 12 months, spinal
      canal cross sectional areas at disc spaces significantly increased from 157.5 to
      294.3 mm(2) (p = 0.012). CONCLUSION: MIS TLIF achieved good clinical outcomes and
      high fusion rates. Our findings show that MIS TLIF performed with a single
      interbody cage and a tubular retractor system can be used as a standard MIS TLIF
      technique.

PMID- 21082049
TI  - Minimally Invasive Muscle Sparing Transmuscular Microdiscectomy : Technique and
      Comparison with Conventional Subperiosteal Microdiscectomy during the Early
      Postoperative Period.
AB  - OBJECTIVE: The authors introduce a minimally invasive muscle sparing
      transmuscular microdiscectomy (MSTM) to treat herniated lumbar disc disease. Its
      results are compared with conventional subperiosteal microdiscectomy (CSM) to
      validate the effectiveness. METHODS: Muscle sparing transmuscular
      microdiscectomy, which involves muscle dissection approach using the natural fat
      cleavage plane between the multifidus to expose the interlaminar space, was
      performed in 23 patients to treat a single level unilateral lumbar radiculopathy.
      The creatine phosphokinase (CPK)-MM serum levels were measured on admission and
      at 1, 3, and 5 days postoperatively. Postoperative pain was evaluated using a 10
      point visual analogue scale (VAS) and recorded on admission and at 1, 3, and 5
      days postoperatively. The results were compared to those from the conventional
      subperiosteal microdiscectomy (43 patients). RESULTS: The CPK-MM levels were
      significantly lower in the serum of the MSTM group compared to the CSM group on
      postoperative days three and five (p = 0.03 and p = 0.02, respectively). The
      clinical scales for back pain using VAS were significantly lower in the MSTM
      group than in the CSM group on postoperative days three (p = 0.04). The mean VAS
      scores for leg pain in both groups showed no significant differences during the
      early postoperative period. CONCLUSION: Muscle sparing transmuscular
      microdiscectomy is a minimally invasive surgical option to treat lumbar
      radiculopathy due to herniated disc. The approach affected minimal injury to
      posterior lumbar supporting structures with alleviated postoperative back pain.

PMID- 21082050
TI  - Comparison between Initial and Recent Surgical Outcome of 15-Year Series of
      Surgically Remediable Epilepsy.
AB  - OBJECTIVE: The aim of this study is to compare the surgical outcome of the
      initial and recent surgical cases, during our 15-years experience, in terms of
      the surgical strategies and the prognostic factors for surgically remediable
      epilepsy. METHODS: We retrospectively reviewed and compared the surgical outcomes
      between the initial 256 (Group I) and recent 139 (Group II) patients according to
      the time period of operation for a total of 518 consecutive epilepsy surgeries at
      our institution since 1992. The patients of the middle intermediate period, which
      were subjected to changed surgical strategies, were excluded. RESULTS: The
      surgical outcome data from the initial and recent groups showed a much improved
      outcome for patients who underwent temporal lobe epilepsy (TLE) surgery over
      time. The number of patients with a good outcome (Engel class I-II) was much
      increased from 87.7% (178 TLE cases of Group I) to 94.8% (79 TLE cases of Group
      II) and this was statistically significant (p = 0.0324) on univariate analysis.
      Other remarkable changes were the decreased performance of intracranial invasive
      studies from 43.5% in Group I to 30.9% in Group II due to the advanced
      neuroimaging tools. The strip/grid ratio was reduced from 131/32 in Group I to
      17/25 in Group II, because of a markedly reduced mesial TLE surgery and an
      increased extratemporal epilepsy surgery. CONCLUSION: Our results show that
      surgical outcome of epilepsy surgery has improved over time and it has shown to
      be efficient to control medically intractable epilepsy. Appropriate patient
      selection, comprehensive preoperative assessments and more extensive resection
      are associated with good postoperative outcomes.

PMID- 21082051
TI  - Selective musculocutaneous neurotomy for spastic elbow.
AB  - OBJECTIVE: The purpose of this study was to investigate the effectiveness and
      outcome of selective musculocutaneous neurotomy (SMcN) for spastic elbow.
      METHODS: We retrospectively reviewed the medical records of 14 patients with
      spasticity of their elbows. The patients were selected using clinical and
      analytical scales, as well as nerve block tests, for assessment. Their mean age
      was 37.29 years (range, 19-63 years). SMcN was performed for these patients, and
      the mean follow-up period was 30.71 months (range, 19-54 months). RESULTS: The
      modified Ashworth scale (MAS) scores recorded before and after the SMcN showed
      that the patients' mean preoperative MAS score of 3.28 +/- 0.12 was improved to
      1.71 +/- 0.12, 1.78 +/- 0.18, 1.92 +/- 0.16 and 1.78 +/- 0.18 at postoperative 3,
      6, 12 months and last follow-up, respectively. On the basis of a visual analogue
      score ranging from 0-100, the patients' mean degree of satisfaction score was
      65.00 +/- 16.52 (range, 30-90). CONCLUSION: We believe that SMcN can be a good
      and effective treatment modality with low morbidity in appropriately selected
      patients who have localized spastic elbow with good antagonist muscles and
      without joint contracture.

PMID- 21082052
TI  - The efficacy of repeated radiofrequency medial branch neurotomy for lumbar facet
      syndrome.
AB  - OBJECTIVE: Radiofrequency (RF) medial branch neurotomy is an effective management
      of lumbar facet syndrome. However, pain may recur after period of time. When pain
      recurs, it can be repeated, but the successful outcome and duration of relief
      from repeated procedures are not clearly known. The objective of this study was
      to determine the success rate and duration of pain relief from repeated
      radiofrequency medial branch neurotomy for lumbar facet syndrome. METHODS: A
      retrospective review of medical records was done on 60 consecutive patients, from
      March of 2006 to February of 2009, who had an initial successful RF neurotomy but
      subsequently underwent repeated procedures due to recurrence of pain. All
      procedures were done in carefully selected patients after at least two responsive
      medial branch nerve blocks. C-arm fluoroscopic guide, impedance, sensory and
      motor threshold monitoring tools were used for the precise placement of
      electrodes. Responses of repeated procedures were compared with initial
      radiofrequency neurotomy for success rates and duration of pain relief. RESULTS:
      There were 48 females and 12 males. Mean age was 52.4 years (range, 26-83). RF
      medial branch neurotomy was done on one side in 38 and both sides in 22 patients,
      each covering at least three segments. Average visual analog scale at last
      procedure was 6.8. Twelve patients had previous lumbar operations, including 4
      patients with instrumentations. Fifty-five patients had two procedures and five
      patients had three procedures. Mean duration of successful pain relief (> 50% of
      previous pain for at least 3 months period) after initial radiofrequency
      neurotomy was 10.9 months (range, 3-28) in 51 (85%) patients. From repeated
      procedures, successful pain relief was seen in 50 (91%) patients with average
      duration of 10.2 months (range, 3-24). Five patients had third procedure, which
      was successful in 4 (80%) patients with mean duration of 9.8 months (range, 5
      16). This was not statistically different from initial results. There were no
      permanent neurological complications from the procedures. CONCLUSION: Results of
      this study indicate that the frequency of success and durations of relief from
      repeated RF medial branch neurotomy for lumbar facet syndrome are similar to
      initial results that provided relatively prolonged period of pain relief without
      major side effects. Each procedure seems to provide successful pain relief for
      about 10 months in more than 85% of carefully selected patients when properly
      done.

PMID- 21082053
TI  - Analysis of complications following decompressive craniectomy for traumatic brain
      injury.
AB  - OBJECTIVE: Adequate management of increased intracranial pressure (ICP) is
      critical in patients with traumatic brain injury (TBI), and decompressive
      craniectomy is widely used to treat refractory increased ICP. The authors
      reviewed and analyzed complications following decompressive craniectomy for the
      management of TBI. METHODS: A total of 89 consecutive patients who underwent
      decompressive craniectomy for TBI between February 2004 and February 2009 were
      reviewed retrospectively. Incidence rates of complications secondary to
      decompressive craniectomy were determined, and analyses were performed to
      identify clinical factors associated with the development of complications and
      the poor outcome. RESULTS: Complications secondary to decompressive craniectomy
      occurred in 48 of the 89 (53.9%) patients. Furthermore, these complications
      occurred in a sequential fashion at specific times after surgical intervention;
      cerebral contusion expansion (2.2 +/- 1.2 days), newly appearing subdural or
      epidural hematoma contralateral to the craniectomy defect (1.5 +/- 0.9 days),
      epilepsy (2.7 +/- 1.5 days), cerebrospinal fluid leakage through the scalp
      incision (7.0 +/- 4.2 days), and external cerebral herniation (5.5 +/- 3.3 days).
      Subdural effusion (10.8 +/- 5.2 days) and postoperative infection (9.8 +/- 3.1
      days) developed between one and four weeks postoperatively. Trephined and post
      traumatic hydrocephalus syndromes developed after one month postoperatively (at
      79.5 +/- 23.6 and 49.2 +/- 14.1 days, respectively). CONCLUSION: A poor GCS score
      (<= 8) and an age of >= 65 were found to be related to the occurrence of one of
      the above-mentioned complications. These results should help neurosurgeons
      anticipate these complications, to adopt management strategies that reduce the
      risks of complications, and to improve clinical outcomes.

PMID- 21082055
TI  - Successful obliteration of unclippable large and giant middle cerebral artery
      aneurysms following extracranial-intracranial bypass and distal clip application.
AB  - Large to giant middle cerebral artery aneurysm is a challenging disease,
      especially when incorporating important perforating arteries. Surgical risk
      increases by perforator infarction and anatomical complexity. In this clinical
      setting, extensive consideration of surgical options is needed. The two cases
      described here were unruptured and had rather stable wall. Because of their large
      and giant size, hardness and incorporated arteries, it was not affordable to
      isolate them by means of clipping or trapping. The procedure as the alternative
      to conventional treatment modalities, extracranial-intracranial bypass followed
      by clipping of only the efferent artery successfully treated the aneurysms.

PMID- 21082054
TI  - A comparative result of ventriculoperitoneal shunt, focusing mainly on gravity
      assisted valve and programmable valve.
AB  - OBJECTIVE: Despite rapid evolution of shunt devices, the complication rates
      remain high. The most common causes are turning from obstruction, infection, and
      overdrainage into mainly underdrainage. We investigated the incidence of
      complications in a consecutive series of hydrocephalic patients. METHODS: From
      January 2002 to December 2009, 111 patients underwent ventriculoperitoneal (VP)
      shunting at our hospital. We documented shunt failures and complications
      according to valve type, primary disease, and number of revisions. RESULTS:
      Overall shunt survival time was 268 weeks. Mean survival time of gravity-assisted
      valve (GAV) was 222 weeks versus 286 weeks for other shunts. Survival time of
      programmable valves (264 weeks) was longer than that of pressure-controlled
      valves (186 weeks). The most common cause for shunt revision was underdrainage
      (13 valves). The revision rate due to underdrainage in patients with GAV (7 of 10
      patients) was higher than that for other valve types. Of 7 patients requiring
      revision for GAV underdrainage, 6 patients were bedridden. The overall infection
      rate was 3.6%, which was lower than reported series. Seven patients demonstrating
      overdrainage had cranial defects when operations were performed (41%), and
      overdrainage was improved in 5 patients after cranioplasty. CONCLUSION: Although
      none of the differences was statistically significant, some of the observations
      were especially notable. If a candidate for VP shunting is bedridden, GAV may not
      be indicated because it could lead to underdrainage. Careful procedure and
      perioperative management can reduce infection rate. Cranioplasty performed prior
      to VP shunting may be beneficial.

PMID- 21082056
TI  - Long-term follow-up clinical courses of cerebellar hemangioblastoma in von hippel
      lindau disease : two case reports and a literature review.
AB  - Although cerebellar hemangioblastomas are histopathologically benign, they yield
      a degree of malignant clinical behavior in long-term follow-up. We present two
      cases of long-term progression of renal cell carcinoma, which had been diagnosed
      as renal cysts during treatment for cerebellar hemangioblastoma. A 14-year-old
      male with von Hippel-Lindau disease was admitted for a cerebellar
      hemangioblastoma with multiple spinal hemangioblastomas and a renal cyst. After
      primary total resection of the cerebellar hemangioblastoma, the patient required
      two further surgeries after 111 and 209 months for a recurrent cerebellar
      hemangioblastoma. Furthermore, he underwent radical nephrectomy as his renal cyst
      had progressed to renal cell carcinoma 209 months after initial diagnosis. A 26
      year-old male presented with multiple cerebellar hemangioblastomas associated
      with von Hippel-Lindau disease and accompanied by multiple spinal
      hemangioblastomas and multiple cystic lesions in the liver, kidney, and pancreas.
      He underwent primary resection of the cerebellar hemangioblastoma in association
      with craniospinal radiation for multiple intracranial/spinal masses.
      Unexpectedly, a malignant glioma developed 83 months after discovery of the
      cerebellar hemangioblastoma. At the same time, renal cell carcinoma, which had
      developed from an initial renal cyst, was diagnosed, and a radical nephrectomy
      was performed. In the view of long term clinical course, cerebellar
      hemangioblastoma associated with von Hipple-Lindau disease may redevelop even
      after primary total resection. In addition, associated lesions such as renal
      cysts may also progress to malignancy after the passing of a sufficient length of
      time.

PMID- 21082057
TI  - Delayed Detected Unexpected Complication of ADCON-L(r) Gel in Lumbar Surgery.
AB  - The ADCON-L gel(r) (Gliatech, Cleveland, OH, USA), a carbohydrate polymer gel,
      has been shown in a controlled clinical study to inhibit postsurgical adhesions
      and improve a patient's clinical outcome. Immediate complication of this gel has
      been reported in the recent literature including back pain, radiculitis and
      durotomy. However, delayed detection of disturbance of muscle healing and
      attachment in late postoperative state has been rarely reported. This report
      documents an unexpected delayed detected complication of the anti-adhesion
      barrier gel, which was used after lumbar discectomy one year ago, with review of
      literature.

PMID- 21082058
TI  - Capillary hemangioma of the thoracic spinal cord.
AB  - Capillary hemangiomas are common soft tissue tumors on the skin or mucosa of the
      head and neck in the early childhood, but very rare in the neuraxis. A 47-year
      old man presented with one month history of back pain on the lower thoracic area,
      radiating pain to both legs, and hypesthesia below T7 dermatome. Thoracic spine
      MRI showed 1*1.3*1.5 cm, well-defined intradural mass at T6-7 disc space level,
      which showed isointensity to spinal cord on T1, heterogeneous isointensity on T2
      weighted images, and homogeneous strong enhancement. The patient underwent T6-7
      total laminotomy, complete tumor removal and laminoplasty. Histologically, the
      mass showed a capsulated nodular lesion composed of capillary-sized vascular
      channels, which were tightly packed into nodules separated by fibrous septa.
      These features were consistent with capillary hemangioma.

PMID- 21082059
TI  - Intradural involvement of multicentric myxoid liposarcoma.
AB  - Liposarcomas are malignant tumors of the soft tissue, with myxoid liposarcoma
      being the second most common subtype, tending to occur in the limbs, particularly
      in the thighs. Myxoid liposarcomas have an intermediate prognosis between well
      differentiated and pleomorphic tumors. Spinal metastasis is usual but intradural
      involvement is extremely rare. We present an unusual case of a multicentric
      myxoid liposarcoma with intradural involvement. A 41-year-old woman complained of
      tingling sensation on her left arm. Radiological evaluation revealed multiple
      masses in her cervical spine, abdominal wall, liver, heart and right thigh, all
      of which were resected. She was histologically diagnosed with small round cell
      myxoid sarcoma and underwent adjuvant chemotherapy. However, magnetic resonance
      imaging analysis after 1 year revealed a large metastatic mass with bony invasion
      at the C6-T1 level. This mass consisted of extradural and intradural components
      causing severe compression of the spinal cord. She underwent resection via a
      posterior facetectomy of C6-7 and an anterior C7 corpectomy. However, the patient
      died of multiple metastases 18 months after the first diagnosis.

PMID- 21082060
TI  - Spinal epidural hematoma after pain control procedure.
AB  - Spinal epidural hematoma is a rare complication associated with pain control
      procedures such as facet block, acupuncture, epidural injection, etc. Although it
      is an uncommon cause of acute myelopathy, and it may require surgical evacuation.
      We report four patients with epidural hematoma developed after pain control
      procedures. Two procedures were facet joint blocks and the others were epidural
      blocks. Pain was the predominant initial symptom in these patients while two
      patients presented with post-procedural neurological deficits. Surgical
      evacuation of the hematoma was performed in two patients while in remaining two
      patients, surgery was initially recommended but not performed since symptoms were
      progressively improved. Three patients showed near complete recovery except for
      one patient who recovered with residual deficits. Although, spinal epidural
      hematoma is a rare condition, it can lead to serious complications like spinal
      cord compression. Therefore, it is important to be cautious while performing
      spinal pain control procedure to avoid such complications. Surgical treatment is
      an effective option to resolve the spinal epidural hematoma.

PMID- 21082061
TI  - Spontaneous regression of a large lumbar disc extrusion.
AB  - Although the spontaneous disappearance or decrease in size of a herniated disc is
      well known, that of a large extruded disc has rarely been reported. This paper
      reports a case of a spontaneous regression of a large lumbar disc extrusion. The
      disc regressed spontaneously with clinical improvement and was documented on a
      follow up MRI study 6 months later. The literature is reviewed and the possible
      mechanisms of spontaneous disc regression are discussed.

PMID- 21082062
TI  - Diffuse pneumocephalus : a rare complication of spinal surgery.
AB  - The common etiologies of pneumocephalus, presence of air in the intracranial
      cavity, are trauma and cranial surgery. Pneumocephalus after spinal surgery is an
      unusual postoperative complication. We report the case of a male 59-year-old man
      who developed a pneumacephalus after posterior lumbar surgery for spinal
      stenosis. Intraoperatively, a cerebrospinal fluid leak following a dural tear was
      noted and immediately repaired. The next day, the patient complained of headache
      and dizziness. Head and lumbar computed tomography scans revealed significant air
      in the frontal region, several cisterns, intraventricle, and extra-dural area in
      the spine canal. Symptoms were spontaneously resolved within 2 weeks with
      conservative management.

PMID- 21082063
TI  - Traumatic Pseudoaneurysm of the Superficial Temporal Artery due to Gardner
      Traction.
AB  - We report a case of pseudoaneurysm of the parietal division of the superficial
      temporal artery (STA) secondary to iatrogenic head injury due to Gardner
      traction. A 54-year-old man presented with a pulsatile, cystic, and painless mass
      in the right anterior temporal region which developed three weeks after head
      fixation via Gardner traction. At the time of discovery, the mass was 10 mm in
      diameter, compressible and disappeared after manual compression of the proximal
      STA. A bruit was audible over the mass, which was thought to be a pseudoaneurysm.
      A computed tomography angiogram (CTA) showed a pseudoaneurysm of the parietal
      division of the right STA. The tip of the pseudoaneurysm was thrombosed and was
      both red and tender. The pseudoaneurysm was thought to be filled with infected
      thrombus, and the mass was resected with ligation of the proximal and distal ends
      of the STA. A pseudoaneurysm of the STA should be suspected when there is a
      history of possible vessel injury, such as a history of head-pin fixation, and
      when a patient presents with a pulsatile, cystic mass near the temple.
      Pseudoaneurysms can be successfully treated by excision.

PMID- 21082064
TI  - Congenital defect of the posterior arch of cervical spine : report of three cases
      and review of the current literature.
AB  - Abnormalities of the posterior arch, including congenitally absent cervical
      pedicle and cervical spondylolysis, are rare entities that are usually found
      incidentally on neck radiographs. It is important to recognize these
      characteristic radiological features because their radiographic appearance may
      cause them to be confused with more serious entities such as fractures, locked
      facets, and tumor-induced bony erosions. Also, it is important to distinguish
      these abnormalities from similar pathologies to prevent the use of inappropriate
      treatment. We report the relevant clinical and radiological findings seen in
      three cases of posterior arch defect after trauma with review of pertinent
      literature.

PMID- 21082065
TI  - Guillain-barre syndrome combined with acute cervical myelopathy.
AB  - Authors describe a patient who developed a myelopathy associated with Guillain
      Barre syndrome and cervical myelopathy. We provide radiological evidence of non
      compressive herniated cervical intervertebral disc with cord signal changes and
      show the clinical and electrophysiological result of coexisting Guillain-Barre
      syndrome and cervical myelopathy. We tried to introduce and review the case of
      Guillain-Barre syndrome which was combined with cervical myelopathy to let us
      recollect the presumptive cause.

PMID- 21082066
TI  - Metronidazole induced encephalopathy in a patient with brain abscess.
AB  - Metronidazole is commonly used for brain abscess but is not well known for its
      neurotoxic complications. Metronidazole-induced encephalopathy (MIEP) is toxic
      encephalopathy associated with the use of metronidazole. We experienced a case of
      brain abscess which developed reversible severe MIEP during treatment period.
      Although MIEP occurs in typical locations, it is not easy to differentiate from
      other conditions such as cerebral infarction, demyelinating diseases and
      metabolic diseases. Neurosurgeons should be aware that severe MIEP can occur
      during the use of metronidazole though it is not common.

PMID- 21082067
TI  - Perspectives on the genetic architecture of divergence in body shape in
      sticklebacks.
AB  - The body shape of fishes encompasses a number of morphological traits that are
      intrinsically linked to functional systems and affect various measures of
      performance, including swimming, feeding, and avoiding predators. Changes in
      shape can allow a species to exploit a new ecological niche and can lead to
      ecological speciation. Body shape results from the integration of morphological,
      behavioral and physiological traits. It has been well established that functional
      interdependency among traits plays a large role in constraining the evolution of
      shape, affecting both the speed and the repeated evolution of particular body
      shapes. However, it is less clear what role genetic or developmental constraints
      might play in biasing the rate or direction of the evolution of body shape. Here,
      we suggest that the threespine stickleback (Gasterosteus aculeatus) is a powerful
      model system in which to address the extent to which genetic or developmental
      constraints play a role in the evolution of body shape in fishes. We review the
      existing data that begins to address these issues in sticklebacks and provide
      suggestions for future areas of research that will be particularly fruitful for
      illuminating the mechanisms that contribute to the evolution of body shape in
      fishes.

PMID- 21082068
TI  - Disentangling the functional roles of morphology and motion in the swimming of
      fish.
AB  - In fishes the shape of the body and the swimming mode generally are correlated.
      Slender-bodied fishes such as eels, lampreys, and many sharks tend to swim in the
      anguilliform mode, in which much of the body undulates at high amplitude. Fishes
      with broad tails and a narrow caudal peduncle, in contrast, tend to swim in the
      carangiform mode, in which the tail undulates at high amplitude. Such fishes also
      tend to have different wake structures. Carangiform swimmers generally produce
      two staggered vortices per tail beat and a strong downstream jet, while
      anguilliform swimmers produce a more complex wake, containing at least two pairs
      of vortices per tail beat and relatively little downstream flow. Are these
      differences a result of the different swimming modes or of the different body
      shapes, or both? Disentangling the functional roles requires a multipronged
      approach, using experiments on live fishes as well as computational simulations
      and physical models. We present experimental results from swimming eels
      (anguilliform), bluegill sunfish (carangiform), and rainbow trout
      (subcarangiform) that demonstrate differences in the wakes and in swimming
      performance. The swimming of mackerel and lamprey was also simulated
      computationally with realistic body shapes and both swimming modes: the normal
      carangiform mackerel and anguilliform lamprey, then an anguilliform mackerel and
      carangiform lamprey. The gross structure of simulated wakes (single versus double
      vortex row) depended strongly on Strouhal number, while body shape influenced the
      complexity of the vortex row, and the swimming mode had the weakest effect.
      Performance was affected even by small differences in the wakes: both
      experimental and computational results indicate that anguilliform swimmers are
      more efficient at lower swimming speeds, while carangiform swimmers are more
      efficient at high speed. At high Reynolds number, the lamprey-shaped swimmer
      produced a more complex wake than the mackerel-shaped swimmer, similar to the
      experimental results. Finally, we show results from a simple physical model of a
      flapping fin, using fins of different flexural stiffness. When actuated in the
      same way, fins of different stiffnesses propel themselves at different speeds
      with different kinematics. Future experimental and computational work will need
      to consider the mechanisms underlying production of the anguilliform and
      carangiform swimming modes, because anguilliform swimmers tend to be less stiff,
      in general, than are carangiform swimmers.

PMID- 21082069
TI  - Antarctic notothenioid fishes: genomic resources and strategies for analyzing an
      adaptive radiation.
AB  - The perciform suborder Notothenoidei provides a compelling opportunity to study
      the adaptive radiation of a marine species-flock in the cold Southern Ocean that
      surrounds Antarctica. To facilitate genome-level studies of the diversification
      of these fishes, we present estimates of the genome sizes of 11 Antarctic species
      and describe the production of high-quality bacterial artificial chromosome (BAC)
      libraries for two, the red-blooded notothen Notothenia coriiceps and the white
      blooded icefish Chaenocephalus aceratus. Our results indicate that evolution of
      phylogenetically derived notothenioid families (e.g., the crown group
      Channichthyidae [icefishes]), was accompanied by genome expansion. Six species
      from the basal family Nototheniidae had C-values between 0.98 and 1.20 pg, a
      range that is consistent with the genome sizes of proposed outgroups (e.g.,
      percids) of the notothenioid suborder. In contrast, four icefishes had C-values
      in the range 1.66-1.83 pg. The BAC libraries VMRC-19 (N. coriiceps) and VMRC-21
      (C. aceratus) comprise 12* and 10* coverage of the respective genomes and have
      average insert sizes of 138 and 168 kb. Paired BAC-end reads representing ~0.1%
      of each genome showed that the repetitive element landscapes of the two genomes
      (13.4% of the N. coriiceps genome and 14.5% for C. aceratus) were similar. The
      availability of these high-quality and well-characterized BAC libraries sets the
      stage for targeted genomic analyses of the unusual anatomical and physiological
      adaptations of the notothenioids, some of which mimic human diseases. Here we
      consider the evolution of secondary pelagicism by various taxa of the group and
      illustrate the utility of Antarctic icefishes as an evolutionary-mutant model of
      human osteopenia (low-mineral density of bones).

PMID- 21082071
TI  - Synthesis of branched Au nanoparticles with tunable near-infrared LSPR using a
      zwitterionic surfactant.
AB  - Asymmetric branched gold nanoparticles are obtained using for the first time in
      the seed-growth approach a zwitterionic surfactant, laurylsulfobetaine, whose
      concentration in the growth solution allows to control both the length to base
      width ratio of the branches and the LSPR position, that can be tuned in the 700
      1100 nm near infrared range.

PMID- 21082070
TI  - A male poecillid's sexually dimorphic body plan, behavior, and nervous system.
AB  - Here we review the literature of a male poecillid's sexually dimorphic body plan,
      behavior, and nervous system, including work dating from the mid 1800s to the mid
      1990s as well as work in press or in preparation for publication. Rosa-Molinar
      described the remodeling of the sexually dimorphic anal fin appendicular support,
      confirmed earlier claims about the development of the male and female secondary
      sex characteristics in the Western Mosquitofish, Gambusia affinis and provided
      for the first time direct embryonic evidence suggesting that remodeling of the
      sexually dimorphic anal fin appendicular support is biphasic. The first process
      begins in embryos and proceeds similarly in immature males and females; the
      second process occurs only in males and results in the anterior transposition of
      the anal fin and its appendicular support to the level of vertebra 11 [Rosa
      Molinar E, Hendricks SE, Rodriguez-Sierra JF, Fritzsch B. 1994. Development of
      the anal fin appendicular support in the western mosquitofish, Gambusia affinis
      (Baird and Girard, 1854): a reinvestigation and reinterpretation. Acta Anat
      151:20-35.] and the formation of a gonopodium used for internal fertilization.
      Studies using high-speed video cameras confirmed and extended Peden's and others'
      observations of copulatory behavior. The cameras showed that circumduction is a
      complex movement combining in a very fast sequence abduction, extension and
      pronation, S-start-type fast-start (defined as torque-thrust), and adduction
      movements. Recent work on the nervous system demonstrated dye-coupling between
      motor neurons and interneurons via gap junctions, suggesting an attractive
      substrate for the rapid motions involved in poecillid copulatory reflexes.

PMID- 21082072
TI  - A new recognition concept using dye sensitized solar cell configuration.
AB  - A bifunctional compound 1 was designed and synthesized, in which the donor-pi
      conjugated-acceptor-cyanoacrylic acid configuration is suited for DSSC, while the
      tetraoxa-azacrown (donor) part also acts as the recognition unit for e.g. Ca(2+)
      and the output of DSSC is utilized as signal transduction, demonstrating a new
      recognition concept using DSSC.

PMID- 21082073
TI  - Nanoflower arrays of rutile TiO2.
AB  - Stacks of multilayered rutile TiO(2) nanoflowers can grow on a titanium film
      through a simple acid vapour oxidation (AVO) method. The growth of this
      interesting hierarchical architecture is due to the formation of rutile {101}
      twinned structures and a subtle mismatching between the lattice spacings of the
      substrate and product.

PMID- 21082074
TI  - Reversible positioning at submicrometre scale of carbon nanotubes mediated by pH
      sensitive poly(amino-methacrylate) patterns.
AB  - The selective adsorption of carbon nanotubes (CNTs) on a pH-reversible PDMAEMA
      patterned gold surface is presented. In acidic conditions, a selective CNTs
      adsorption onto the polymer brushes is obtained due to ammonium-pi interactions.
      The reversible behavior was shown by successive treatments in both alkaline and
      acidic solutions with CNTs.

PMID- 21082075
TI  - Competing S(N)2 and E2 reaction pathways for hexachlorocyclohexane degradation in
      the gas phase, solution and enzymes.
AB  - Quantum chemistry calculations have been used alongside experimental kinetic
      analysis to investigate the competition between S(N)2 and E2 mechanisms for the
      dechlorination of hexachlorocyclohexane isomers, revealing that enzyme
      specificity reflects the intrinsic reactivity of the various isomers.

PMID- 21082076
TI  - Post-functionalization of ATRP polymers using both thiol/ene and thiol/disulfide
      exchange chemistry.
AB  - In this communication, we report on a new route to the functionalization of ATRP
      polymers exploiting their halide end-groups, which were converted successfully
      into reactive disulfide end-groups, using sodium methanethiosulfonate. The
      resultant disulfide-terminated polymers could then be reacted with different
      functional thiols to yield functional polymers exploiting either thiol/disulfide
      exchange chemistry or thiol/ene "click" reactions.

PMID- 21082077
TI  - Gas-induced solid state transformation of an organic lattice: from nonporous to
      nanoporous.
AB  - A well-known organic host, tris-o-phenylenedioxycyclotriphosphazene, exists in
      two polymorphic guest-free forms: the thermodynamic nonporous high-density phase
      and the kinetic nanoporous low-density phase. Simple pressurization of the high
      density phase with CO(2) brings a solid-state transformation to the low density
      phase, resulting in significant expansion of the crystal volume by 23%.

PMID- 21082078
TI  - Biodistribution and toxicity of engineered gold nanoparticles: a review of in
      vitro and in vivo studies.
AB  - Recent advances in wet chemical synthesis and biomolecular functionalization of
      gold nanoparticles have led to a dramatic expansion of their potential biomedical
      applications, including biosensorics, bioimaging, photothermal therapy, and
      targeted drug delivery. As the range of gold nanoparticle types and their
      applications continues to increase, human safety concerns are gaining attention,
      which makes it necessary to better understand the potential toxicity hazards of
      these novel materials. Whereas about 80 reports on the in vivo biodistribution
      and in vitro cell toxicity of gold nanoparticles are available in the literature,
      there is lack of correlation between both fields and there is no clear
      understanding of intrinsic nanoparticle effects. At present, the major obstacle
      is the significant discrepancy in experimental conditions under which
      biodistribution and toxicity effects have been evaluated. This critical review
      presents a detailed analysis of data on the in vitro and in vivo biodistribution
      and toxicity of most popular gold nanoparticles, including atomic clusters and
      colloidal particles of diameters from 1 to 200 nm, gold nanoshells, nanorods, and
      nanowires. Emphasis is placed on the systematization of data over particle types
      and parameters, particle surface functionalization, animal and cell models,
      organs examined, doses applied, the type of particle administration and the time
      of examination, assays for evaluating gold particle toxicity, and methods for
      determining the gold concentration in organs and distribution of particles over
      cells. On the basis of a critical analysis of data, we arrive at some general
      conclusions on key nanoparticle parameters, methods of particle surface
      modification, and doses administered that determine the type and kinetics of
      biodistribution and toxicity at cellular and organismal levels (197 references).

PMID- 21082079
TI  - Aliphatic polyester polymer stars: synthesis, properties and applications in
      biomedicine and nanotechnology.
AB  - A critical review: the ring-opening polymerization of cyclic esters provides
      access to an array of biodegradable, bioassimilable and renewable polymeric
      materials. Building these aliphatic polyester polymers into larger macromolecular
      frameworks provides further control over polymer characteristics and opens up
      unique applications. Polymer stars, where multiple arms radiate from a single
      core molecule, have found particular utility in the areas of drug delivery and
      nanotechnology. A challenge in this field is in understanding the impact of
      altering synthetic variables on polymer properties. We review the synthesis and
      characterization of aliphatic polyester polymer stars, focusing on polymers
      originating from lactide, epsilon-caprolactone, glycolide, beta-butyrolactone and
      trimethylene carbonate monomers and their copolymers including coverage of
      polyester miktoarm star copolymers. These macromolecular materials are further
      categorized by core molecules, catalysts employed, self-assembly and degradation
      properties and the resulting fields of application (262 references).

PMID- 21082081
TI  - Cyclohexylcyanine: a new aliphatic phthalocyanine analogue.
AB  - In this report, we present cyclohexylcyanine, a phthalocyanine analogue with two
      cyclohexane units incorporated into the backbone of the macrocycle; in the free
      base, the ionizable protons lie on the periphery of the ring, and when metalated
      with silver the macrocycle binds to the metal via these same meso nitrogen atoms.

PMID- 21082080
TI  - Identification of dihydropyridines that reduce cellular tau levels.
AB  - A series of dihydropyridines were identified that have an effect on the
      accumulation of tau, an important target in Alzheimer's disease. The
      dihydropyridine collection was expanded using the Hantzsch multicomponent
      reaction to develop preliminary structure-activity relationships.

PMID- 21082082
TI  - Influence of blend microstructure on bulk heterojunction organic photovoltaic
      performance.
AB  - The performance of organic photovoltaic devices based upon bulk heterojunction
      blends of donor and acceptor materials has been shown to be highly dependent on
      the thin film microstructure. In this tutorial review, we discuss the factors
      responsible for influencing blend microstructure and how these affect device
      performance. In particular we discuss how various molecular design approaches can
      affect the thin film morphology of both the donor and acceptor components, as
      well as their blend microstructure. We further examine the influence of polymer
      molecular weight and blend composition upon device performance, and discuss how a
      variety of processing techniques can be used to control the blend microstructure,
      leading to improvements in solar cell efficiencies.

PMID- 21082083
TI  - Polycyclic aromatic hydrocarbons and organochlorine pesticides in surface soils
      from the Qinghai-Tibetan plateau.
AB  - Eighty eight surface soil samples were collected from the Qinghai-Tibetan Plateau
      (QTP) for determination of polycyclic aromatic hydrocarbons (PAHs) and
      organochlorine pesticides (OCPs), including dichlorodiphenyltrichloroethane and
      metabolites (DDXs) and hexachlorocyclohexane isomers (HCHs). The measured
      concentrations were 51.8 +/- 38.5 ng g(-1), 0.329 +/- 0.818 ng g(-1), and 0.467
      +/- 0.741 ng g(-1) as means and standard deviations of PAHs, DDXs, and HCHs,
      respectively, which were 1-2 orders of magnitude lower than those reported for
      eastern China. Significant differences were also revealed among four sub-areas
      within QTP. PAHs detected in the samples from the remote sub-areas of T'ang-ku
      la/Hoh Xil Mountains and along the Qinghai-Tibet highway in the west and
      northwest of QTP were 1 order of magnitude lower than those from Lhasa and east
      Qinghai. The differences in soil OCPs among the sub-areas were 2-7 times. Soil
      PAHs were significantly correlated with emission density and soil organic carbon
      content (SOC), while OCPs were correlated significantly with the population
      density and SOC. Based on the calculated backward air mass trajectories and
      geographical distributions of emission and population, it was revealed that PAHs
      and OCPs accumulated in the soils in the west and northwest QTP were primarily
      from long-range transport and may represent the background levels of East Asia.
      This part of QTP can also serve as an important receptor area for regional or
      even global long-range transport study. The elevated concentrations of PAHs and
      OCPs in Lhasa and east Qinghai were mainly from local sources, while PAHs from
      adjacent Lanzhou area also contributed considerably to the accumulation of PAHs
      in east Qinghai.

PMID- 21082085
TI  - Magnetic nanobeads decorated by thermo-responsive PNIPAM shell as medical
      platforms for the efficient delivery of doxorubicin to tumour cells.
AB  - Medical nanoplatforms based on clusters of superparamagnetic nanoparticles
      decorated with a PNIPAM thermo-responsive shell have been synthesized and used as
      drug carriers for doxorubicin (DOXO), a common chemotherapeutic agent. The
      nanosystem here developed has a total diameter below 200 nm and exploits the
      temperature responsive behaviour of the PNIPAM polymeric shell for the controlled
      loading and release of DOXO. The system has been tested in vitro on tumour cells
      and it clearly demonstrates the effectiveness of drug polymer encapsulation and
      time-dependent cell death induced by the doxorubicin release. Comparative
      cellular studies of the DOXO loaded nanoplatform in the presence or absence of an
      external magnet (0.3 T) showed the synergic effect of accumulation and enhanced
      toxicity of the system, when magnetically guided, resulting in the enhanced
      efficacy of the system.

PMID- 21082084
TI  - Miniaturized ionization gas sensors from single metal oxide nanowires.
AB  - Gas detection experiments were performed with individual tin dioxide (SnO2)
      nanowires specifically configured to observe surface ion (SI) emission response
      towards representative analyte species. These devices were found to work at much
      lower temperatures (T~280  degrees C) and bias voltages (V~2 V) than their micro
      counterparts, thereby demonstrating the inherent potential of individual
      nanostructures in building functional nanodevices. High selectivity of our
      miniaturized sensors emerges from the dissimilar sensing mechanisms of those
      typical of standard resistive-type sensors (RES). Therefore, by employing this
      detection principle (SI) together with RES measurements, better selectivity than
      that observed in standard metal oxide sensors could be demonstrated. Simplicity
      and specificity of the gas detection as well as low-power consumption make these
      single nanowire devices promising technological alternatives to overcome the
      major drawbacks of solid-state sensor technologies.

PMID- 21082086
TI  - Molecular dynamics simulation of NMR powder lineshapes of linear guests in
      structure I clathrate hydrates.
AB  - We perform molecular dynamics simulations (up to 6 ns) for the structure I
      clathrate hydrates of linear molecules CS, CS(2), OCS, and C(2)H(2) in large
      cages at different temperatures in the stability range to determine the angular
      distribution and dynamics of the guests in the large cages. The long axes of
      linear guest molecules in the oblate large structure I clathrate hydrate cages
      are primarily confined near the equatorial plane of the cage rather than axial
      regions. This non-uniform spatial distribution leads to well-known anisotropic
      lineshapes in the solid-state NMR spectra of the guest species. We use the
      dynamic distribution of guest orientations in the cages during the MD simulations
      at different temperatures to predict the (13)C NMR powder lineshapes of the
      guests in the large cages. The length of the guests and intermolecular
      interactions of the guests in the water cages determine the angular distribution
      and the mobility of the guests in the sI large cages at different temperatures.
      At low temperatures the range of motion of the guests in the cages are limited
      and this is reflected in the skew of the predicted (13)C lineshapes. As the guest
      molecules reach the fast motion limit at higher temperatures, the lineshapes for
      CS, OCS, and C(2)H(2) are predicted to have the "standard" powder lineshapes of
      guest molecules.

PMID- 21082087
TI  - Spatially resolved cathodoluminescence of individual BN-coated CaS:Eu nanowires.
AB  - Luminescence properties of individual BN-coated CaS:Eu nanowires have been
      studied by high-spatial-resolution cathodoluminescence (CL) spectroscopy. A broad
      red light-emitting band from an individual nanowire has been observed. Detailed
      local CL studies on the nanowires reveal spatial variations of luminescence from
      the structure surfaces toward their cores. Such variations are attributed to the
      different Eu2+ ions surroundings within the surface and core nanowire regions.
      The attractive luminescence properties are meaningful for fundamental studies of
      nanoscaled luminescent materials and may be of interest for novel optoelectronic
      applications.

PMID- 21082088
TI  - Angular distributions and angular momentum alignment of O((3)P(J)) atoms formed
      in the photolysis of O(2)via the Herzberg continuum.
AB  - Sliced velocity-map imaging has been used to measure photofragment scattering
      distributions for the O((3)P(2)) and O((3)P(1)) products of O(2) photolysis
      following laser excitation into the Herzberg continuum between 205 and 241 nm.
      The images were analysed to extract the photofragment spatial anisotropy
      parameter, beta, together with the alignment parameters a(?), a(?), a(?), and
      Re[a(?, ?)]. Our alignment measurements bridge the gap between the recent 193 nm
      measurement of Brouard et al., Phys. Chem. Chem. Phys., 2006, 8, 5549 and those
      of Alexander et al., J. Chem. Phys., 2003, 118, 10566 at 222 and 237 nm, and
      extend out to the threshold at 241 nm. Our measured parameters show no strong
      dependence on photolysis wavelength. Near the threshold we were able to separate
      the contributions from the O((3)P(2)) + O((3)P(2)) and O((3)P(2)) + O((3)P(1))
      channels, and found significantly different photofragment alignments for the two
      cases.

PMID- 21082089
TI  - Chemoselective quantum control of carbonyl bonds in Grignard reactions using
      shaped laser pulses.
AB  - Grignard reactants like methylmagnesium chloride are not selective with respect
      to different carbonyl bonds. We present a theoretical study where shaped laser
      pulses are utilized to prefer specific bonds in a mixture of more than one
      carbonyl reactant. A mixture of cyclohexanone and cyclopentanone has been chosen
      as a representative example. The light pulse is supposed to provide the
      activation energy and to adopt the function of a protecting group. The control
      aim is to stretch exclusively the C-O bond of one compound to the length required
      in the Grignard transition state. To guarantee an experimentally realizable
      bandwidth for the unshaped pulse, we use our recently developed optimal control
      theory algorithm, which allows the simultaneous optimization of the light field
      in the time and frequency domain. Highly selective picosecond control pulses
      could be optimized in the infrared regime suggesting that laser assisted
      chemoselectivity is possible to a large extent. To obtain control not only on the
      final product but also on the excitation mechanism, various initial conditions
      and frequency restrictions were investigated.

PMID- 21082090
TI  - Water-driven ligations using cyclic amino squarates: a class of useful SN1-like
      reactions.
AB  - We report a class of water-soluble and -stable cyclic amino squarates that ligate
      with cysteine or lysine residues without side-products in an entirely aqueous
      environment. The ligations include addition-elimination reactions that are
      promoted by water in a way similar to S(N)1 reactions. The structural versatility
      of the reactants allows the potential recognition of selected amino acid residues
      on proteins.

PMID- 21082091
TI  - Microwave assisted covalent functionalization of C(60)@SWCNT peapods.
AB  - The covalent functionalization of the external wall of C(60)@SWCNT peapods, by in
      situ generated aryl diazonium salts, assisted by microwave irradiation is
      reported. Spectroscopic, thermal and microscopy characterization was performed.
      Electrochemistry revealed the three reversible reductions of encapsulated C(60),
      however, shifted towards positive potentials when compared with those of intact
      C(60).

PMID- 21082093
TI  - A crossed molecular beam study on the reaction of methylidyne radicals
      [CH(X(2)Pi)] with acetylene [C(2)H(2)(X(1)Sigma(g)(+))]-competing C(3)H(2) + H
      and C(3)H + H(2) channels.
AB  - We carried out the crossed molecular beam reaction of ground state methylidyne
      radicals, CH(X(2)Pi), with acetylene, C(2)H(2)(X(1)Sigma(g)(+)), at a nominal
      collision energy of 16.8 kJ mol(-1). Under single collision conditions, we
      identified both the atomic and molecular hydrogen loss pathways forming C(3)H(2)
      and C(3)H isomers, respectively. A detailed analysis of the experimental data
      suggested the formation of c-C(3)H(2) (31.5 +/- 5.0%), HCCCH/H(2)CCC (59.5 +/-
      5.0%), and l-HCCC (9.0 +/- 2.0%). The reaction proceeded indirectly via complex
      formation and involved the unimolecular decomposition of long-lived propargyl
      radicals to form l-HCCC plus molecular hydrogen and HCCCH/H(2)CCC plus atomic
      hydrogen. The formation of c-C(3)H(2) was suggested to be produced via
      unimolecular decomposition of the cyclopropenyl radical, which in turn could be
      accessed via addition of the methylidyne radical to both carbon atoms of the
      acetylene molecule or after an initial addition to only one acetylenic carbon
      atom via ring closure. This investigation brings us closer to unraveling of the
      reaction of important combustion radicals-methylidyne-and the connected
      unimolecular decomposition of chemically activated propargyl radicals. This also
      links to the formation of C(3)H and C(3)H(2) in combustion flames and in the
      interstellar medium.

PMID- 21082092
TI  - Spectroelectrochemical studies of hole percolation on functionalised
      nanocrystalline TiO2 films: a comparison of two different ruthenium complexes.
AB  - We report the application of spectroelectrochemical techniques to compare the
      hole percolation dynamics of molecular networks of two ruthenium bipyridyl
      complexes adsorbed onto mesoporous, nanocrystalline TiO(2) films. The percolation
      dynamics of the ruthenium complex cis-di(thiocyanato)(2,2'-bipyridyl-4,4'
      dicarboxylic acid)-(2,2'-bipyridyl-4,4'-tridecyl) ruthenium(II), N621, is
      compared with those observed for an analogous dye with an additional tri-phenyl
      amine (TPA) donor moiety, cis-di(thiocyanato)(2,2'-bipyridyl-4,4'-dicarboxylic
      acid)-(2,2'-bipyridyl-4,4'-bis(vinyltriphenylamine)) ruthenium(II), HW456. The in
      situ oxidation of these ruthenium complexes adsorbed to the TiO(2) films is
      monitored by cyclic voltammetry and voltabsorptometry, whilst the dynamics of
      hole (cation) percolation between adsorbed ruthenium complexes is monitored by
      potentiometric spectroelectrochemistry and chronoabsorptometry. The hole
      diffusion coefficient, D(eff), is shown to be dependent on the dye loading on the
      nanocrystalline TiO(2) film, with a threshold observed at ~60% monolayer surface
      coverage for both dyes. The hole diffusion coefficient of HW456 is estimated to
      be 2.6 * 10(-8) cm(2)/s, 20-fold higher than that obtained for the control N621,
      attributed to stronger electronic coupling between the TPA moieties of HW456
      accelerating the hole percolation dynamics. The presence of mercuric ions,
      previously shown to bind to the thiocyanates of analogous ruthenium complexes,
      resulted in a quenching of the hole percolation for N621/TiO(2) films and an
      enhancement for HW456/TiO(2) films. These results strongly suggest that the hole
      percolation pathway is along the overlapped neighbouring -NCS groups for the N621
      molecules, whereas in HW456 molecules cation percolation proceeds between
      intermolecular TPA ligands. These results are discussed in the context of their
      relevance to the process of dye regeneration in dye sensitised solar cells, and
      to the molecular wiring of wide bandgap inorganic materials for battery and
      sensing applications.

PMID- 21082094
TI  - Classification and management issues of Greek lakes under the European Water
      Framework Directive: a DPSIR approach.
AB  - The European Water Framework Directive (WFD) establishes a framework for the
      protection of water bodies. The aim of the Water Framework Directive (WFD) is to
      ensure sustainable management of groundwater, freshwater and marine water in the
      European Union, such that a minimum "good ecological status" will be obtained by
      2015. We used background morphometric, hydrologic, physico-chemical and
      biological data, in order to highlight the ecological status of the natural Greek
      lakes using also the Driving-Pressure-State-Impact-Response (DPSIR) approach in
      order to link the driving forces and further the pressures with the present state
      of the lakes' ecosystems. In addition detailed biodiversity and habitat typology
      data are provided. The assessment of the DPSIR approach under the view of WFD
      provided a quite clear identification of pressures and the subsequent impacts of
      the qualitative status of the Greek lakes.

PMID- 21082109
TI  - Stability of small mesoporous silica nanoparticles in biological media.
AB  - In this work, sub-50 nm pegylated mesoporous silica nanoparticles prepared with
      hydrothermal treatment are shown to have long-term stability in various media at
      both room and physiological temperature. Compared to bare mesoporous silica
      nanoparticles, the highly pegylated mesoporous silica nanoparticles show
      significantly improved biocompatibility and decreased macrophage uptake, making
      these nanoparticles viable for in vivo stealth drug delivery applications.

PMID- 21082095
TI  - Indoor and outdoor concentrations of fine particles, particle-bound PAHs and
      volatile organic compounds in Kaunas, Lithuania.
AB  - This complex study presents indoor and outdoor levels of air-borne fine
      particles, particle-bound PAHs and VOCs at two urban locations in the city of
      Kaunas, Lithuania, and considers possible sources of pollution. Two sampling
      campaigns were performed in January-February and March-April 2009. The mean
      outdoor PM(2.5) concentration at Location 1 in winter was 34.5 +/- 15.2 ug m(-3)
      while in spring it was 24.7 +/- 12.2 ug m(-3); at Location 2 the corresponding
      values were 36.7 +/- 21.7 and 22.4 +/- 19.4 ug m(-3), respectively. In general
      there was little difference between the PM concentrations at Locations 1 and 2.
      PM(2.5) concentrations were lower during the spring sampling campaign. These PM
      concentrations were similar to those in many other European cities; however, the
      levels of most PAHs analysed were notably higher. The mean sum PAH concentrations
      at Locations 1 and 2 in the winter campaign were 75.1 +/- 32.7 and 32.7 +/- 11.8
      ng m(-3), respectively. These differences are greater than expected from the
      difference in traffic intensity at the two sites, suggesting that there is
      another significant source of PAH emissions at Location 1 in addition to the
      traffic. The low observed indoor/outdoor (I/O) ratios indicate that PAH emissions
      at the locations studied arise primarily from outdoor sources. The buildings at
      both locations have old windows with wooden frames that are fairly permissive in
      terms of air circulation. VOC concentrations were mostly low and comparable to
      those reported from Sweden. The mean outdoor concentrations of VOC's were: 0.7 +/
      0.2, 3.0 +/- 0.8, 0.5 +/- 0.2, 3.5 +/- 0.3, and 0.2 +/- 0.1 ug m(-3), for
      benzene, toluene, ethylbenzene, sum of m-, p-, o-xylenes, and naphthalene,
      respectively. Higher concentrations of VOCs were observed during the winter
      campaign, possibly due to slower dispersion, slower chemical transformations
      and/or the lengthy "cold start" period required by vehicles in the wintertime. A
      trajectory analysis showed that air masses coming from Eastern Europe carried
      significantly higher levels of PM(2.5) compared to masses from other regions, but
      the PAHs within the PM(2.5) are of local origin. It has been suggested that
      street dust, widely used for winter sanding activities in Eastern and Central
      European countries, may act not only as a source of PM, but also as source of
      particle-bound PAHs. Other potential sources include vehicle exhaust, domestic
      heating and long-range transport.

PMID- 21082110
TI  - A porphyrin-related macrocycle from carbazole and pyridine building blocks:
      synthesis and metal coordination.
AB  - In this communication, we report the synthesis of a novel porphyrin-related
      macrocycle. The core modifications result in aromatic building blocks connected
      exclusively via aryl-aryl bonds. The concept of synthesis permits the formation
      of a cavity similar to that of a porphyrin combined with the ability to bind
      metal ions to provide neutral metal complexes.

PMID- 21082111
TI  - On/off luminescence vapochromic selective sensing of benzene and its methylated
      derivatives by a trinuclear silver(I) pyrazolate sensor.
AB  - {[3,5-(CF(3))(2)Pz]Ag}(3) (1) films exhibit selective/reversible sensing of small
      organic-molecule (SAM) vapors, which readily switch-on bright-green (benzene or
      toluene) or bright-blue (mesitylene) luminescence that switches-off upon vapor
      removal. Vapors of electron-deficient SAMs or non-aromatic solvents did not
      attain luminescence switching and were not adsorbed.

PMID- 21082112
TI  - Ru-catalyzed aerobic oxidative coupling of arylboronic acids with arenes.
AB  - A Ru-catalyzed oxidative coupling of arenes with boronic acids using molecular
      oxygen via direct C-H activation is reported. Both the scope and the mechanism of
      the process are discussed.

PMID- 21082113
TI  - Synthetic oligodeoxynucleotide purification by polymerization of failure
      sequences.
AB  - Synthetic oligodeoxynucleotide is purified by capping failure sequences with an
      acrylated phosphoramidite followed by polymerization and product extraction. The
      method is suitable for large scale oligonucleotide drug purification.

PMID- 21082114
TI  - Synthesis, characterization and photovoltaic properties of poly(thiophenevinylene
      alt-benzobisoxazole)s.
AB  - Herein we report the synthesis of two solution processible, conjugated polymers
      containing the benzobisoxazole moiety. The polymers were characterized using (1)H
      NMR, UV-Vis and fluorescence spectroscopy. Thermal gravimetric analysis shows
      that the polymers do not exhibit significant weight loss until approximately 300 
      degrees C under nitrogen. Cyclic voltammetry shows that the polymers have
      reversible reduction waves with estimated LUMO levels at -3.02 and -3.10 eV
      relative to vacuum and optical bandgaps of 2.04-2.17 eV. Devices based on blends
      of the copolymers and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) exhibited
      modest power conversion efficiencies. Theoretical models reveal that there is
      poor electron delocalization along the polymer backbone, leading to poor
      performance. However, the energy levels of these polymers indicate that the
      incorporation of benzobisoxazoles into the polymer backbone is a promising
      strategy for the synthesis of new materials.

PMID- 21082115
TI  - Holstein-Peirls-Hubbard trimer as a model for quadrupolar two-photon absorbing
      dyes.
AB  - The linear and nonlinear optical properties of a Donor-Acceptor-Donor system have
      been investigated by using a two-electron three-point-site model system. Some
      basic features of electron correlations are included in the model by means of a
      bi-electronic density matrix. The polarizabilities and second
      hyperpolarizabilities have been computed with a modified version of the
      Collective Electronic Oscillators (CEO) method which allowed us to include the
      electron-phonon coupling. Both singly- and doubly-excited states are taken into
      account in the computation of (hyper-)polarizabilities. The effects of electron
      phonon coupling on the two-photon absorption and on the third harmonic generation
      in the infrared region are discussed.

PMID- 21082116
TI  - Conformational transition of DNA bound to Hfq probed by infrared spectroscopy.
AB  - Hfq is a bacterial protein involved in RNA metabolism. Besides this, Hfq's role
      in DNA restructuring has also been suggested. Since this mechanism remains
      unclear, we examined the DNA conformation upon Hfq binding by combining
      vibrational spectroscopy and neutron scattering. Our analysis reveals that Hfq,
      which preferentially interacts with deoxyadenosine rich sequences, induces
      partial opening of dA-dT sequences accompanied by sugar repuckering of the dA
      strand and hence results in a heteronomous A/B duplex. Sugar repuckering is
      probably correlated with a global dehydration of the complex. By taking into
      account Hfq's preferential binding to A-tracts, which are commonly found in
      promoters, potential biological implications of Hfq binding to DNA are discussed.

PMID- 21082117
TI  - The photodissociation of NO(2) by visible and ultraviolet light.
AB  - We present velocity map images of the NO, O((3)P(J)) and O((1)S(0))
      photofragments from NO(2) excited in the range 7.6 to 9.0 eV. The molecule was
      initially pumped with a visible photon between 2.82-2.95 eV (440-420 nm), below
      the first dissociation threshold. A second ultraviolet laser with photon energies
      between 4.77 and 6.05 eV (260-205 nm) was used to pump high-lying excited states
      of neutral NO(2) and/or probe neutral photoproducts. Analysis of the kinetic
      energy release spectra revealed that the NO photofragments were predominantly
      formed in their ground electronic state with little kinetic energy. The
      O((3)P(J)) and O((1)S(0)) kinetic energy distributions were also dominated by
      kinetically 'cold' fragments. We discuss the possible excitation schemes and
      conclude that the unstable photoexcited states probed in the experiment were
      Rydberg states coupled to dissociative valence states. We compare our results
      with recent time-resolved studies using similar excitation and probe photon
      energies.

PMID- 21082118
TI  - Synthesis and structural characterization of group 6 transition metal complexes
      with terminal fluoromethylidyne (CF) ligands; a DFT/NBO/NRT comparison of bonding
      characteristics of terminal NO, CF and CH ligands.
AB  - A family of group 6 transition metal complexes M(C(5)R(5))(CO)(2)(CF) [M = Cr,
      Mo, W; R = H, Me] with terminal fluoromethylidyne ligands have been synthesized
      through the reduction of the corresponding trifluoromethyl precursors with
      potassium graphite or magnesium graphite. They have been characterized
      spectroscopically and in some cases crystallographically, although the structures
      show disorder between the CO and CF ligands. The M[triple bond]CF subunit reacts
      as a triple bond to form cluster complexes containing MU(3)-CF ligands on
      reaction with Co(2)(CO)(8). Computational (DFT/NBO/NRT) studies on
      M(C(5)H(5))(CO)(2)(CF) [M = Cr, Mo, W] and the corresponding cationic fragments
      M(CO)(2)(XY)(+) illustrate significant differences in the metal-ligand bonding
      between CF and its isoelectronic analogue NO, as well as with its hydrocarbon
      analogue CH.

PMID- 21082119
TI  - Panchromatic ruthenium sensitizer based on electron-rich heteroarylvinylene pi
      conjugated quaterpyridine for dye-sensitized solar cells.
AB  - The first example of a heteroarylvinylene pi-conjugated quaterpyridine Ru(II)
      sensitizer (N1044) was synthesized and used in dye-sensitized solar cells; the
      dye has an effective panchromatic absorption band, covering the entire visible
      spectrum up to the NIR region, and superior electrochemical characteristics
      (HOMO/LUMO and bandgap energies) with respect to previous representative Ru(II)
      bi- and quaterpyridine sensitizers. A record IPCE curve ranging from 360 to 920
      nm has been measured with a maximum of 65% at 646 nm and still 33% efficiency at
      800 nm; this leads to substantially increased photocurrent (19.2 mA cm(-2)) when
      compared to the prototype N719 Ru(II) sensitizer.

PMID- 21082120
TI  - Antifouling marine natural products.

PMID- 21082121
TI  - Conformationally rigid aromatic amino acids as potential building blocks for
      abiotic foldamers.
AB  - This communication describes the development of conformationally constrained
      unnatural aromatic amino acids, constructed on rigid backbone wherein the
      carboxyl and amino groups project in two dimensions (planes) on the aromatic
      framework. Such a feature offers the possibility of design and development of
      conformationally ordered synthetic oligomers with intriguing structural
      architectures distinct from those classically observed. Furthermore, such amino
      acids will have the potential to extend the conformational space available for
      foldamer design with diverse backbone conformation and structural architectures.

PMID- 21082122
TI  - "Click-made" biaryl-linker improving efficiency in protein labelling for the
      membrane target protein of a bioactive compound.
AB  - We report on the design, synthesis and assessment of a novel biaryl-linked (BArL)
      molecular probe for the exploration of low-abundant target proteins for bioactive
      compounds based on the activity based protein profiling (ABPP) approach.
      Surprisingly, the performance of the BArL probe was better than that of the
      stepwise tagging approach that is considered to be the most effective method used
      in ABPP study.

PMID- 21082123
TI  - Light relief: photochemistry and medicine.
AB  - Photomedicine as a 'modern' subject began in the late 1880's, and currently
      encompasses the effects of light upon the skin, diagnostic uses of light,
      therapies using non-laser light, and the use of lasers. Effects of light on the
      skin include production of Vitamin D, tanning, ageing of the skin, and the skin
      cancers basal cell and squamous cell carcinomas, and malignant melanoma.
      Diagnostic uses of light include luminescence [photo and chemi] in immunoassays,
      fluorescence in cell sorting, and the various forms of fluorescence microscopy,
      including confocal, fluorescence lifetime imaging [FLIM], and single molecule.
      Therapies include the PUVA treatment of psoriasis and vitiligo, blue light curing
      of neonatal jaundice, and photoinactivation of microbes. Laser treatments include
      ablative corrective eye surgery, general 'bloodless' surgery, and, of most
      importance photochemically, the various treatments using sensitisers and laser
      light known as photodynamic therapy, PDT. We concentrate here on discussion of
      future developments in PDT, concluding that the main advance will be through
      targeted PDT, in which the tissue to be destroyed receives the photosensitiser in
      a highly selective fashion. Strategies to achieve this highlighted here are the
      use of monoclonal antibody fragments selected for tumour cell targets, and two
      photon spatial selection.

PMID- 21082124
TI  - Biomineral nanoparticles are space-filling.
AB  - Sea urchin biominerals have been shown to form from aggregating nanoparticles of
      amorphous calcium carbonate (ACC), which then crystallize into macroscopic single
      crystals of calcite. Here we measure the surface areas of these biominerals and
      find them to be comparable to those of space-filling macroscopic geologic calcite
      crystals. These biominerals differ from synthetic mesocrystals, which are
      invariably porous. We propose that space-filling ACC is the structural precursor
      for echinoderm biominerals.

PMID- 21082125
TI  - Stereoselective synthesis of the C15-C26 fragment of the antitumor agent (-)
      dictyostatin.
AB  - The synthesis of the C15-C26 fragment of (-)-dictyostatin is reported in 10 steps
      and 28% overall yield. The key steps are the two stereoselective sulfoxide
      directed processes: a Reformatsky-type reaction and a beta-keto sulfoxide
      reduction.

PMID- 21082126
TI  - Kinetics and mechanism of the anilinolyses of aryl dimethyl, methyl phenyl and
      diphenyl phosphinates.
AB  - The reactions of Z-aryl dimethyl (1), methyl phenyl (2), and diphenyl (3)
      phosphinates with X-anilines in dimethyl sulfoxide at 60.0  degrees C are studied
      kinetically. Kinetic results yield the primary normal deuterium kinetic isotope
      effects (DKIEs) involving deuterated aniline (XC(6)H(4)ND(2)) nucleophiles,
      k(H)/k(D) = 1.03-1.17, 1.15-1.29, and 1.24-1.51, and the cross-interaction
      constants (CICs), rho(XZ) = 0.37, 0.34, and 0.65 for 1, 2, and 3, respectively.
      The steric effects of the ligands (R(1) and R(2)) on reaction rates play a role,
      but are relatively much smaller compared to other phosphinate systems. A stepwise
      mechanism with a rate-limiting leaving group expulsion from the intermediate is
      proposed on the basis of the CICs positive signs. The dominant frontside
      nucleophilic attack through a hydrogen-bonded, four-center-type transition state
      is proposed on the basis of primary normal DKIEs and large magnitudes of the CICs
      for 2 and 3, while both frontside and backside attack are proposed on the basis
      of relatively small primary normal DKIEs for 1.

PMID- 21082127
TI  - P1,P2-diimidazolyl derivatives of pyrophosphate and bis-phosphonates--synthesis,
      properties, and use in preparation of dinucleoside tetraphosphates and analogs.
AB  - P(1),P(2)-Diimidazolyl derivatives of pyrophosphate and halomethylene-bis
      phosphonates have been synthesized and characterized, and the mechanism of their
      formation was studied. These reagents enable synthesis of dinucleoside
      tetraphosphates and tetraphosphonates conveniently and in high yields.

PMID- 21082128
TI  - A novel synthesis of oxazolidine-2,4-diones via an efficient fixation of CO2 with
      3-aryl-2-alkynamides.
AB  - A very mild protocol for fixation of carbon dioxide with 2-alkynamides in DMSO at
      30  degrees C using a CO(2) balloon in the presence of K(2)CO(3) has been
      developed, which leads to an efficient assembly of oxazolidine-2,4-diones. It is
      observed that the regioselectivity was controlled by the aryl group.

PMID- 21082129
TI  - Total synthesis of (-)-20-epiuleine via stereocontrolled one-pot asymmetric
      azaelectrocyclization followed by novel 1,4-addition reaction.
AB  - The first asymmetric total synthesis of an indole alkaloid, (-)-20-epiuleine,
      containing the 2,3,4-trisubstituted piperidine core, was achieved using a
      stereocontrolled one-pot asymmetric 6pi-azaelectrocyclization followed by a
      stereoselective 1,4-addition reaction of the unsaturated ester with a Grignard
      reagent resulting from the novel neighboring participation of the hydroxyl group
      in cis-aminoindanol as a chiral nitrogen source.

PMID- 21082130
TI  - FeCl3-promoted alkylation of indoles by enamides.
AB  - An efficient iron-promoted alkylation of indoles with enamides has been
      accomplished under mild reaction conditions. The reaction proceeded with
      remarkable regioselectivity leading exclusively to substitution by indoles at
      alpha-position of enamides.

PMID- 21082131
TI  - Mutated variant of Candida antarctica lipase B in (S)-selective dynamic kinetic
      resolution of secondary alcohols.
AB  - An (S)-selective dynamic kinetic resolution of secondary alcohols, employing a
      mutated variant of Candida antarctica lipase B (CalB) gave products in 84-88%
      yield and in 90-97% ee.

PMID- 21082132
TI  - A direct and efficient preparation of 1-phenyltetrazol-5-yl sulfides from
      alcohols.
AB  - Treatment of primary or secondary alcohols with 1-phenyl-1(H)-tetrazole-5-thiol
      and [Me(2)NCHSEt](+) BF(4)(-) leads directly and cleanly to 1-phenyl-1(H)
      tetrazol-5-yl sulfides.

PMID- 21082133
TI  - Synthesis of thioethers via metal-free reductive coupling of tosylhydrazones with
      thiols.
AB  - A metal-free procedure for the synthesis of thioethers is described via the base
      promoted reductive coupling of tosylhydrazones with thiols through an insertion
      of a carbene into the S-H bond.

PMID- 21082134
TI  - Per(poly)fluoroalkanesulfinamides assisted diastereoselective three-component
      inverse-electron-demand aza Diels-Alder reaction.
AB  - A highly diastereoselective three-component inverse-electron-demand aza Diels
      Alder reaction assisted by per(poly)fluoro-alkanesulfinamides is presented,
      providing a broad spectrum of highly functionalized piperidine derivatives with
      excellent endo/exo and facial diastereoselectivities. The electron-withdrawing
      perfluoroalkyl groups are crucial for the success of this reaction under mild
      conditions and facilitate monitoring the process and stereoselectivities of the
      reaction. The synthetic potential of these cycloadducts is also highlighted.

PMID- 21082135
TI  - Functionalisation of heteroaromatic N-oxides using organic superbase catalyst.
AB  - Functionalisation of quinoline N-oxide was investigated using phophazene base as
      a catalyst; alkynylation and heteroarylation at 2-position were successfully
      achieved via nucleophilic addition-elimination process.

PMID- 21082136
TI  - Structural and dynamic properties of oxygen vacancies in perovskite oxides-
      analysis of defect chemistry by modern multi-frequency and pulsed EPR techniques.
AB  - Multi-frequency and pulsed electron paramagnetic resonance (EPR) provides a
      sensitive spectroscopic tool to elucidate the defect structure of transition
      metal doped perovskite oxides, as well as to monitor dynamic processes of oxygen
      vacancies in these materials. In this regard, high-frequency EPR spectrometers
      and pulsed EPR techniques such as the hyperfine sublevel correlation experiment
      (HYSCORE) may now routinely be used for dedicated investigations, providing
      considerably more insight than the application of standard continuous-wave EPR.
      Recent results include the formation of defect complexes between acceptor-type
      transition-metal centers with either one or two oxygen vacancies for the reason
      of charge compensation. Furthermore, such defect complexes follow the domain
      switching upon poling ferroelectric compounds with correspondingly high electric
      fields. On the other hand, multi-valent manganese functional centers provide
      trapping centers for electronic and ionic charge carriers (e', ) such that
      valency altered acceptor states or defect complexes are formed. Additionally, the
      trapping of charge carriers at the intrinsic 'reduced' B-site ions, and , can be
      observed by means of EPR spectroscopy.

PMID- 21082137
TI  - Zinc coverage dependent structure of PdZn surface alloy.
AB  - Catalytic performances of alloy and surface alloy are sensitive to the surface
      structures and composition. In this paper we present an overall survey of the
      surface structure of Pd(111) covered with different amount of Zn using Monte
      Carlo simulations. We demonstrate that the composition of PdZn surface alloy is
      Zn coverage dependent: the surface concentration of Zn increases with the
      increase of the deposited Zn. At one or multi-layer of zinc deposited Pd(111), a
      multilayer 1 : 1 PdZn surface alloy will be formed. Surface alloy islands
      dominated by palladium are formed at submonolayer Zn coverage. At very low zinc
      coverage, small palladium ensembles of 3 to 5 Pd atoms exist preferentially on
      the Pd(111) surface. Our simulated results which are consistent with the
      pertinent experiments indicate that the unusual high-temperature desorption peak
      of formaldehyde observed experimentally has likely originated from the small
      surface ensembles induced by deposited Zn.

PMID- 21082138
TI  - Controlling the mechanism of fulvene S(1)/S(0) decay: switching off the stepwise
      population transfer.
AB  - Direct quantum dynamics simulations were performed to model the radiationless
      decay of the first excited state S(1) of fulvene. The full space of thirty normal
      mode nuclear coordinates was explicitly considered. By default, ultrafast
      internal conversion takes place centred on the higher-energy planar region of the
      S(1)/S(0) conical intersection seam, giving the stepwise population transfer
      characteristic of a sloped surface crossing, and leading back to the ground state
      reactant. Two possible schemes for controlling whether stepwise population
      transfer occurs or not-either altering the initial geometry distribution or the
      initial momentum composition of the photo-excited wavepacket-were explored. In
      both cases, decay was successfully induced to occur in the lower-energy
      twisted/peaked region of the crossing seam, switching off the stepwise population
      transfer. This absence of re-crossing is a direct consequence of the change in
      the position on the intersection at which decay occurs (our target for control),
      and its consequences should provide an experimentally observable fingerprint of
      this system.

PMID- 21082140
TI  - Triclorosilane-mediated stereoselective synthesis of beta-amino esters and their
      conversion to highly enantiomerically enriched beta-lactams.
AB  - A highly stereoselective trichlorosilane-mediated reduction of N-benzyl enamines
      was developed; the combination of a low cost, easy to make metal-free catalyst
      and an inexpensive chiral auxiliary allowed to perform the reaction on substrates
      with different structural features often with total control of the
      stereoselectivity. By easy deprotection through hydrogenolysis followed by
      conversion of beta-aminoester to 2-azetidinones, the synthesis of
      enantiomerically pure beta-lactams (>98% e.e.) was successfully accomplished.

PMID- 21082139
TI  - Tubulin-binding dibenz[c,e]oxepines as colchinol analogues for targeting tumour
      vasculature.
AB  - Various methoxy- and hydroxy-substituted dibenz[c,e]oxepines were prepared via
      the copper(I)-induced coupling of ether-tethered arylstannanes or the dehydrative
      cyclisation of 1,1'-biphenyl-2,2'-dimethanols, assembled using the Ullmann cross
      coupling of ortho-bromoaryl carbonyl compounds. The dibenzoxepines were screened
      for their ability to inhibit tubulin polymerisation and the in vitro growth of
      K562 human chronic myelogenous leukemia cells. The most active was 5,7-dihydro
      3,9,10,11-tetramethoxydibenz[c,e]oxepin-4-ol, whose tubulin inhibitory and
      cytotoxicity (IC(50)) values were 1 MUM and 40 nM, respectively.

PMID- 21082141
TI  - Synthesis of novel sugar-lactam conjugates using the Aube reaction.
AB  - An efficient and convenient method for the synthesis of sugar-lactam conjugates
      is reported starting from readily available sugar azides using the Aube reaction.
      Cyclic azido alcohols are used in the Aube reaction for the first time in a
      carbohydrate setting. The resulting glycoconjugates could be further used to
      increase the chemical diversity on the sugar backbone, and may find potential
      applications as glycomimetics, peptidomimetics, in glycotargeting and in CNS drug
      delivery.

PMID- 21082142
TI  - Photodegradation of organic pollutants catalyzed by iron species under visible
      light irradiation.
AB  - The green oxidation technology is the most economically attractive and
      environmentally friendly oxidation technique in the treatment of organic
      pollutants. Photocatalytic degradation of organic pollutants by iron species is a
      desired green oxidation technique due to using hydrogen peroxide or ideally
      molecular oxygen as oxidant and water as solvent. However, the system has some
      disadvantages. The reaction has to be performed in acidic conditions in order to
      avoid Fe ion precipitation and iron sludge will be accumulated in the reaction.
      Moreover, the utilization of H(2)O(2) means a high cost and risks in the storage
      and transportation and organic pollutants can not be completely mineralized. In
      this perspective, we report a systematic investigation of the improvement in the
      Fenton system for treatment of organic pollutants in water. Several strategies
      have been studied on the Fenton system for overcoming the above mentioned
      shortcomings and enhance the efficiency. For example, in order to extend the
      application of the Fenton system and perform it at neutral pH, iron complexes
      were used to replace the Fe(2+)/Fe(3+). Moreover, iron complexes have a strong
      absorption in the visible region, which leads to decomposition of colorless
      organic pollutants under visible light irradiation. Iron complexes with special
      structures can activate molecular O(2) instead of H(2)O(2) under mild conditions
      and the supported iron species maintains a high catalytic activity after repeated
      use and can be reused simply by filtration. Finally, prospects for further work
      required to be performed for its practical application is discussed.

PMID- 21082143
TI  - Top-down fabrication of nano-scaled Bi2Se(0.3)Te(2.7) associated by
      electrochemical Li intercalation.
AB  - A convenient top-down method for preparation of Bi(2)Se(0.3)Te(2.7) crystalline
      nano-particles has been demonstrated. It contains two steps: (1) lithium was
      intercalated between the van der Waals bonded quintuple-layers by electrochemical
      process inside lithium ion batteries with precisely controlled speed and amount;
      (2) subsequent alcohol exposure of Li(x)Bi(2)Se(0.3)Te(2.7) to make the
      intercalated Li atoms explode like atom-scaled bombs and exfoliate the original
      micro/macro scaled materials into nano-scaled single crystalline particles with
      sizes around 10 nm. The intercalation process does not cost external energy, and
      can be scaled up by amplification of the intercalation devices.

PMID- 21082144
TI  - Silver nanoprobe for sensitive and selective colorimetric detection of dopamine
      via robust Ag-catechol interaction.
AB  - Dopamine exhibits intriguing reactivity with silver nanoparticles through Ag
      catechol interaction, which results in non-crosslinking AgNP aggregation, thus
      providing a novel approach for colorimetric detection of dopamine with high
      sensitivity and selectivity.

PMID- 21082145
TI  - Enhanced catalyst recovery in an aqueous copper-free Sonogashira cross-coupling
      reaction.
AB  - We report the synthesis of a superparamagnetic nanoparticle MNP (gamma
      Fe(2)O(3)/polymer) supported dendritic catalyst based on a bulky electron-rich
      phosphine Pd(II) complex. The high reactivity of this catalyst is described in a
      copper-free Sonogashira C-C cross-coupling reaction in water, and the significant
      role of surfactant additives is highlighted in the recovery study.

PMID- 21082158
TI  - Cationic nucleolipids as efficient siRNA carriers.
AB  - We synthesized five novel uridine-based cationic nucleolipids, introducing basic
      amino acid residues at the 5' position of uridine, through 1,3-dipolar
      cycloaddition, and hydrophobic alkyl moieties at the 2' and 3' positions, through
      carbamate linkages. Their lipoplexes delivered siRNAs efficiently to cells, in
      vitro, without any severe toxicity.

PMID- 21082159
TI  - "Is this case of a very rare disease work-related?" A review of reported cases of
      Pacinian neuroma.
AB  - OBJECTIVE: In response to a request for a medicolegal opinion from an orthopaedic
      technician with pacinian neuroma of the hand, we conducted a systematic review of
      reported cases designed to assess whether this rare disease could be considered
      to be work-related. METHODS: We used Medline, Embase, Google Scholar, Google, and
      a manual search to identify reports of histologically confirmed pacinian neuroma
      of the hand manifesting after 15 years of age. Cases with available information
      (from article/authors) on personal history were considered eligible. We tabulated
      information on age/gender; localization and histopathologic features;
      signs/symptoms; history of local trauma; occupation, sports/hobbies or other
      physical exposures; right- or left-handedness; and outcome. RESULTS: We found 44
      eligible cases (including the present referral). Of these, 21 (48%) followed a
      trauma [<6 months from onset/presentation (N=7); 0.5-2 years from onset (N=6); >=
      2 years from onset (N=7); and timing unknown (N=1)] involving the same anatomic
      site. Three of these 21 traumas definitely occurred at work, and a further 2
      cases occurred at the site of definite work-related repetitive microtrauma.
      CONCLUSIONS: The results reinforce the concept that pacinian neuroma of the hand
      can follow local trauma or repetitive microtrauma. Implicated traumas were either
      recent or remote, and they sometimes occurred while performing manual tasks at
      work. We concluded that the referred case could plausibly be considered work
      related.

PMID- 21082160
TI  - [Elbow prosthetics].

PMID- 21082161
TI  - [Minimally invasive treatment of geriatric and osteoporotic femur fractures with
      polyaxial locking implants (NCB-DF(r))].
AB  - BACKGROUND: Periprosthetic femur fractures in elderly patients are a challenging
      surgical procedure. The aim of this study was a prospective evaluation of
      minimally invasive implantation of non-contact bridging (NCB-DF(r)) plates.
      PATIENTS AND METHODS: A total of 30 osteosynthesis procedures in 29 patients
      (average age 76 years and mean ASA 2.9) with complex femur fractures were
      registered, 19 fractures were periprosthetic and osteoporosis was present in 17
      bones. In 25 patients a minimally invasive percutaneous procedure was performed
      using a standardized technique. An x-ray examination and clinical follow-up were
      performed after 6, 12 and 24 weeks. RESULTS: The early complications (14% in
      total) included 1 plate breakage after 16 weeks as well as 3 minor revisions for
      screw length correction. The x-ray follow-up after 24 weeks showed a secondary
      extension deficit of 10 degrees  and 15 degrees  in the knee joint in 2 patients,
      respectively. CONCLUSION: The NCB-DF(r) implantation using a standardized
      minimally invasive technique in periprosthetic femur fractures is a safe
      alternative in elderly patients. In this very sensitive population the early
      revision rate within the first 24 weeks is noticeable lower compared to similar
      procedures.

PMID- 21082162
TI  - Heavy metal contamination in bore water due to industrial pollution and polluted
      and non polluted sea water intrusion in Thoothukudi and Tirunelveli of South
      Tamil Nadu, India.
AB  - This study investigates the pollution vulnerability of bore water in the coastal
      region of Tirunelveli and Thoothukudi in the state of Tamilnadu, India. There are
      no industries in the Tirunelveli Coastal area whereas there are many industries
      in SIPCOT (State Industries Promotion Corporation of Tamilnadu) Thoothukudi, and
      coastal area of Thoothukudi. Bore water from the SIPCOT, coastal area of
      Thoothukudi and Tirunelveli were collected periodically from July 2006 to May
      2008 for this study. These samples were tested and analyzed to find the
      concentrations of sodium, magnesium, aluminium, potassium, calcium, copper,
      cadmium, mercury and lead. The toxic cadmium concentration was found in the range
      of 0.00-0.22 mg Kg-1 at SIPCOT 2 in November 2007, mercury 0.00-0.024 mg Kg-1 and
      lead 0.00-0.02 mg Kg-1 in SIPCOT 2 in January 2008. The level of contamination is
      higher than the WHO limits of drinking water standards; but copper and aluminium
      content are within the limit. On the other hand, the samples taken from bores in
      Tirunelveli coastal area are non-polluted, and the analysis shows that all the
      metals are within the limits of WHO standard.

PMID- 21082163
TI  - The effect of graft fixation sequence on force distribution in double-bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: This paper investigated the effect of graft fixation sequence on knee
      joint biomechanics after a double-bundle ACL reconstruction. METHOD: Two
      independently published biomechanical studies that investigated the biomechanics
      of double-bundle ACL reconstructions using similar robotic testing systems were
      compared. In each study, ten human cadaveric knees were tested under three
      different conditions: intact, ACL deficient, and ACL reconstructed using a double
      bundle technique with the anteromedial (AM) graft fixed at 60 degrees  of flexion
      and the posterolateral (PL) graft fixed at full extension. In one study (Study
      A), the AM graft was fixed first; while in another study (Study B), the PL graft
      was fixed first. Knee kinematics, in situ forces of the ACL and the ACL grafts
      were measured under two loading conditions: an anterior tibial load of 134 N and
      a combined tibial torques (10 N.m valgus and 5 N.m internal tibial torques) in
      both studies. RESULT: When AM graft was fixed first, the in situ force of the AM
      graft was lower than the native AM bundle at all flexion angles. The in situ
      force in the PL graft, however, was higher than the native PL bundle at all
      flexion angles. When the PL graft was fixed first, the in situ force of the AM
      graft was higher than the native AM bundle, while the in situ forces of the PL
      graft were lower than the native PL bundle at all flexion angles. Both studies
      demonstrated that the double-bundle ACL reconstructions can closely restore the
      normal knee joint kinematics. CONCLUSION: Even though the grafts were fixed using
      similar initial tensions and at same flexion angles, the sequence of fixing the
      two grafts in a double-bundle ACL reconstruction could alter the in situ forces
      in the grafts and affect the knee kinematics. These data imply that in clinical
      application of a double-bundle ACL reconstruction, the sequence of graft fixation
      should be an important surgical parameter.

PMID- 21082165
TI  - Avoiding tunnel collisions between fibular collateral ligament and ACL
      posterolateral bundle reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the risk of tunnel collisions
      of the fibular collateral ligament (FCL) and posterolateral bundle anterior
      cruciate ligament (PLB-ACL) tunnels during a combined FCL and double-dundle (DB)
      ACL reconstruction. METHODS: Thirty-six 4th-generation synthetic femurs
      (Sawbones, Pacific Research Laboratories, Vashon, WA) were utilized, and two
      different femur sizes were used. A FCL tunnel and a PLB-ACL tunnel were reamed on
      each femur. The tunnels of synthetic specimens that did not have a collision were
      filled with an epoxy resin augmented with BaSO(4) and radiographic evaluation,
      and Multidetector CT exams of the specimens were performed. RESULTS: The rate of
      tunnel collision when the FCL tunnel was reamed to a depth of 30 mm was 75 and
      69.4% for the 25 mm depth. There was a significantly increased risk of tunnel
      collision when the FCL tunnel was reamed proximally with coronal angulations of
      20 degrees  and 40 degrees . No collisions were noted when the FCL tunnel was
      reamed parallel to the distal condylar line and with axial angulations of 20
      degrees  and 40 degrees . CONCLUSION: This study provides new insight into tunnel
      positioning during a combined FCL and DB-ACL reconstruction. The results show
      that a concomitant FCL injury do not represent a contraindication to perform a DB
      ACL reconstruction as long as the FCL tunnel is reamed with no proximal
      angulation and is directed anteriorly with an axial angulation between 20 degrees
      and 40 degrees .

PMID- 21082164
TI  - Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use.
AB  - Tissue repair in musculoskeletal lesions is often a slow and sometimes incomplete
      process. In sports patients or professional athletes, the impact of
      musculoskeletal lesions on life and work is great, and the fast recovery of full
      efficiency and return to competition is of primary importance. The clinical
      improvement offered by available treatments is not always sufficient for highly
      demanding patients to return to their previous level of activity. The search for
      a minimally invasive solution to improve the status of the chondral surface of
      the injured joint is therefore highly desirable, especially in these patients.
      Platelet-rich plasma (PRP) is a procedure that allows to obtain a natural
      concentration of autologous growth factors. The attractive possibility to use the
      patients' own growth factors to enhance reparative process in tissues with low
      healing potential, the promising preliminary clinical findings and the safety of
      these methods, explain the wide application of this biological approach. The aim
      of this review is to analyse the existing published studies to look for
      scientific evidence in preclinical studies or in the results obtained through PRP
      application in humans that supports the efficacy of PRP and its use for the
      treatment of tendinous, ligamentous, cartilaginous and muscular injuries. The
      analysis of the literature shows promising preclinical results but contradictory
      clinical findings for the treatment of sport injuries. High-quality studies are
      required to confirm these preliminary results and provide scientific evidence to
      support its use.

PMID- 21082166
TI  - Arthroscopy-assisted fracture fixation.
AB  - PURPOSE: the purpose of this article was to systematically analyze the results of
      published studies in the literature which evaluated the use of arthroscopically
      assisted techniques in intra-articular fracture fixation. METHODS: published
      investigations to date were analyzed by classifying them according to joints that
      were involved with intra-articular fractures including: knee, ankle, hip,
      shoulder, elbow, and wrist joints. The results were studied to assess the
      feasibility, efficiency, and outcomes of arthroscopy-assisted fracture fixation.
      RESULTS: arthroscopy-assisted techniques have been used successfully for the
      treatment of fractures of the tibial plateau, tibial eminence, malleoli, pilon,
      calcaneus, femoral head, glenoid, greater tuberosity, distal clavicle, radial
      head, coronoid, distal radius, and scaphoid. The major advantages of arthroscopic
      fracture fixation over open methods are direct visualization of the intra
      articular space, decreased invasiveness, and the possibility for multitask
      interventions through which fixation of the fracture, and repair of the soft
      tissues and the cartilage can be performed simultaneously. The time-consuming and
      technically demanding nature of the procedures with a prolonged learning curve
      and limited fixation alternatives are the main disadvantages of this technique.
      CONCLUSION: arthroscopic fixation is increasingly utilized for certain intra
      articular fracture types due to the minimally invasive nature of the procedures
      and high accuracy. Randomized controlled trials are needed to justify wider use
      of arthroscopy-assisted techniques for treatment of intra-articular fractures.

PMID- 21082167
TI  - Effects of mutations within surface-exposed loops in the pore-forming domain of
      the Cry9Ca insecticidal toxin of Bacillus thuringiensis.
AB  - The pore-forming domain of Bacillus thuringiensis insecticidal Cry toxins is
      formed of seven amphipathic alpha-helices. Because pore formation is thought to
      involve conformational changes within this domain, the possible role of its
      interhelical loops in this crucial step was investigated with Cry9Ca double
      mutants, which all share the previously characterized R164A mutation, using a
      combination of homology modeling, bioassays and electrophysiological
      measurements. The mutations either introduced, neutralized or reversed an
      electrical charge carried by a single residue of one of the domain I loops. The
      ability of the 28 Cry9Ca double mutants to depolarize the apical membrane of
      freshly isolated Manduca sexta larval midguts was tested in the presence of
      either midgut juice or a cocktail of protease inhibitors because these conditions
      had been shown earlier to greatly enhance pore formation by Cry9Ca and its R164A
      single-site mutant. Most mutants retained toxicity toward neonate larvae and a
      pore-forming ability in the electrophysiological assay, which were comparable to
      those of their parental toxin. In contrast, mutants F130D, L186D and V189D were
      very poorly toxic and practically inactive in vitro. On the other hand, mutant
      E129A depolarized the midgut membrane efficiently despite a considerably reduced
      toxicity, and mutant Q192E displayed a reduced depolarizing ability while
      conserving a near wild-type toxicity. These results suggest that the conditions
      found in the insect midgut, including high ionic strength, contribute to
      minimizing the influence of surface charges on the ability of Cry9Ca and probably
      other B. thuringiensis toxins to form pores within their target membrane.

PMID- 21082168
TI  - Evolution of prokaryotic genes by shift of stop codons.
AB  - De novo origin of coding sequence remains an obscure issue in molecular
      evolution. One of the possible paths for addition (subtraction) of DNA segments
      to (from) a gene is stop codon shift. Single nucleotide substitutions can destroy
      the existing stop codon, leading to uninterrupted translation up to the next stop
      codon in the gene's reading frame, or create a premature stop codon via a
      nonsense mutation. Furthermore, short indels-caused frameshifts near gene's end
      may lead to premature stop codons or to translation past the existing stop codon.
      Here, we describe the evolution of the length of coding sequence of prokaryotic
      genes by change of positions of stop codons. We observed cases of addition of
      regions of 3'UTR to genes due to mutations at the existing stop codon, and cases
      of subtraction of C-terminal coding segments due to nonsense mutations upstream
      of the stop codon. Many of the observed stop codon shifts cannot be attributed to
      sequencing errors or rare deleterious variants segregating within bacterial
      populations. The additions of regions of 3'UTR tend to occur in those genes in
      which they are facilitated by nearby downstream in-frame triplets which may serve
      as new stop codons. Conversely, subtractions of coding sequence often give rise
      to in-frame stop codons located nearby. The amino acid composition of the added
      region is significantly biased, compared to the overall amino acid composition of
      the genes. Our results show that in prokaryotes, shift of stop codon is an
      underappreciated contributor to functional evolution of gene length.

PMID- 21082169
TI  - Characterization of maltase clusters in the genus Drosophila.
AB  - To reveal evolutionary history of maltase gene family in the genus Drosophila, we
      undertook a bioinformatics study of maltase genes from available genomes of 12
      Drosophila species. Molecular evolution of a closely related glycoside hydrolase,
      the alpha-amylase, in Drosophila has been extensively studied for a long time.
      The alpha-amylases were even used as a model of evolution of multigene families.
      On the other hand, maltase, i.e., the alpha-glucosidase, got only scarce
      attention. In this study, we, therefore, investigated spatial organization of the
      maltase genes in Drosophila genomes, compared the amino acid sequences of the
      encoded enzymes and analyzed the intron/exon composition of orthologous genes. We
      found that the Drosophila maltases are more numerous than previously thought (ten
      instead of three genes) and are localized in two clusters on two chromosomes (2L
      and 2R). To elucidate the approximate time line of evolution of the clusters, we
      estimated the order and dated duplication of all the 10 genes. Both clusters are
      the result of ancient series of subsequent duplication events, which took place
      from 352 to 61 million years ago, i.e., well before speciation to extant
      Drosophila species. Also observed was a remarkable intron/exon composition
      diversity of particular maltase genes of these clusters, probably a result of
      independent intron loss after duplication of intron-rich gene ancestor, which
      emerged well before speciation in a common ancestor of all extant Drosophila
      species.

PMID- 21082170
TI  - Evolution of the relaxin/insulin-like gene family in placental mammals:
      implications for its early evolution.
AB  - The relaxin (RLN) and insulin-like (INSL) gene family is a group of genes
      involved in a variety of physiological roles that includes bone formation,
      testicular descent, trophoblast development, and cell differentiation. This
      family appears to have expanded in vertebrates relative to non-vertebrate
      chordates, but the relative contribution of whole genome duplications (WGDs) and
      tandem duplications to the observed diversity of genes is still an open question.
      Results from our comparative analyses favor a model of divergence post vertebrate
      WGDs in which a single-copy progenitor found in the last common ancestor of
      vertebrates experienced two rounds of WGDs before the functional differentiation
      that gave rise to the RLN and INSL genes. One of the resulting paralogs was
      subsequently lost, resulting in three proto-RLN/INSL genes on three separate
      chromosomes. Subsequent rounds of tandem gene duplication and divergence
      originated the set of paralogs found on a given cluster in extant vertebrates.
      Our study supports the hypothesis that differentiation of the RLN and INSL genes
      took place independently in each RLN/INSL cluster after the two WGDs during the
      evolutionary history of vertebrates. In addition, we show that INSL4 represents a
      relatively old gene that has been apparently lost independently in all
      Euarchontoglires other than apes and Old World monkeys, and that RLN2 derives
      from an ape-specific duplication.

PMID- 21082172
TI  - Left atrial myxoma in a child with unique presentation: chest pain.
AB  - We present a 16-year-old girl who presented with chest pain. Given her obesity
      and positive family history, she was felt to have atherosclerotic heart disease.
      However, an echocardiogram showed an atrial myxoma, which prompted surgical
      excision. This case supports the routine use of echocardiography and widened
      differential diagnosis when presented with pediatric chest pain.

PMID- 21082173
TI  - Primary repair of aortopulmonary window with an interrupted aortic arch in a very
      low-birth-weight premature neonate.
AB  - The aortopulmonary window concomitant with an interrupted aortic arch is a rare
      occurrence. We successfully performed an emergency one-stage surgical repair of
      the aortopulmonary window (type 1) concomitant with an interrupted aortic arch
      (type A) in the case of a very low-birth-weight (1230-g) premature 2-day-old
      neonate. We describe the diagnosis, surgery, and postoperative course of this
      rare occurrence.

PMID- 21082171
TI  - Proteome evolution and the metabolic origins of translation and cellular life.
AB  - The origin of life has puzzled molecular scientists for over half a century. Yet
      fundamental questions remain unanswered, including which came first, the
      metabolic machinery or the encoding nucleic acids. In this study we take a
      protein-centric view and explore the ancestral origins of proteins. Protein
      domain structures in proteomes are highly conserved and embody molecular
      functions and interactions that are needed for cellular and organismal processes.
      Here we use domain structure to study the evolution of molecular function in the
      protein world. Timelines describing the age and function of protein domains at
      fold, fold superfamily, and fold family levels of structural complexity were
      derived from a structural phylogenomic census in hundreds of fully sequenced
      genomes. These timelines unfold congruent hourglass patterns in rates of
      appearance of domain structures and functions, functional diversity, and
      hierarchical complexity, and revealed a gradual build up of protein repertoires
      associated with metabolism, translation and DNA, in that order. The most ancient
      domain architectures were hydrolase enzymes and the first translation domains had
      catalytic functions for the aminoacylation and the molecular switch-driven
      transport of RNA. Remarkably, the most ancient domains had metabolic roles, did
      not interact with RNA, and preceded the gradual build-up of translation. In fact,
      the first translation domains had also a metabolic origin and were only later
      followed by specialized translation machinery. Our results explain how the
      generation of structure in the protein world and the concurrent crystallization
      of translation and diversified cellular life created further opportunities for
      proteomic diversification.

PMID- 21082174
TI  - Early echocardiographic findings in beta-thalassemia intermedia patients using
      standard and tissue Doppler methods.
AB  - Heart complications are among the serious problems of patients with beta
      thalassemia intermedia. This study aimed to evaluate myocardial function in these
      patients. Clinical parameters and both standard Doppler and pulsed Doppler tissue
      imaging parameters were compared in 51 beta-thalassemia intermedia patients (mean
      age, 17.05 +/- 5.8 years) and 20 normal subjects (mean age, 17.81 +/- 7.35 years,
      p = 0.98). In 11 patients (21.5%), pulmonary artery hypertension was detected. M
      mode echocardiographic findings such as ejection fraction and fractional
      shortening did not show statistically significant changes (p > 0.005). Pulsed
      Doppler showed a significant difference in the early (E) to late diastolic (A)
      velocity ratio of the tricuspid and mitral valve between the patients and the
      control subjects (p < 0.05). In the pulsed tissue Doppler study, the peak
      systolic velocity of the septum (Ss), the peak atrial velocity of the septum
      (Aas), the peak systolic velocity of the tricuspid annulus (St), the peak early
      diastolic velocity of the tricuspid annulus (Eat), and the peak late diastolic
      velocity of the tricuspid annulus (Aat) were increased significantly (p < 0.05).
      The pulse tissue Doppler of the lateral mitral annulus did not change
      significantly (p > 0.005). The peak systolic velocity of the posterior wall and
      the peak late diastolic velocity of the anterior wall changed significantly (p <
      0.05). This study showed that beta-thalassemia intermedia patients with normal M
      mode and two-dimensional echocardiography had statistically significant changes
      in pulsed Doppler and pulsed tissue Doppler imaging.

PMID- 21082175
TI  - Trisomy 13 in a 9-year-old girl with left ventricular noncompaction.

PMID- 21082176
TI  - Percutaneous transcatheter closure of a paravalvular leak in a 20-month old
      child.

PMID- 21082177
TI  - Disturbance of glucose homeostasis after pediatric cardiac surgery.
AB  - This study aimed to evaluate the time course of perioperative blood glucose
      levels of children undergoing cardiac surgery for congenital heart disease in
      relation to endogenous stress hormones, inflammatory mediators, and exogenous
      factors such as caloric intake and glucocorticoid use. The study prospectively
      included 49 children undergoing cardiac surgery. Blood glucose levels, hormonal
      alterations, and inflammatory responses were investigated before and at the end
      of surgery, then 12 and 24 h afterward. In general, blood glucose levels were
      highest at the end of surgery. Hyperglycemia, defined as a glucose level higher
      than 8.3 mmol/l (>150 mg/dl) was present in 52% of the children at the end of
      surgery. Spontaneous normalization of blood glucose occurred in 94% of the
      children within 24 h. During surgery, glucocorticoids were administered to 65% of
      the children, and this was the main factor associated with hyperglycemia at the
      end of surgery (determined by univariate analysis of variance). Hyperglycemia
      disappeared spontaneously without insulin therapy after 12-24 h for the majority
      of the children. Postoperative morbidity was low in the study group, so the
      presumed positive effects of glucocorticoids seemed to outweigh the adverse
      effects of iatrogenic hyperglycemia.

PMID- 21082178
TI  - A 2-year assessment of the main environmental factors driving the free-living
      bacterial community structure in Lake Bourget (France).
AB  - Despite the considerable attention that has been paid to bacterioplankton over
      recent decades, the dynamic of aquatic bacterial community structure is still
      poorly understood, and long-term studies are particularly lacking. Moreover, how
      the environment governs diversity patterns remains a key issue in aquatic
      microbial ecology. In this study, we used denaturing gradient gel electrophoresis
      of PCR-amplified partial 16S rRNA gene fragments and multivariable statistical
      approaches to explore the patterns of change in the free-living bacterial
      community in the mesotrophic and mono-meromictic Lake Bourget (France). A monthly
      sampling was conducted over two consecutive years (2007 and 2008) and at two
      different depths characterizing the epi- and hypolimnion of the lake (2 and 50 m,
      respectively). Temporal shifts in the bacterial community structure followed
      different patterns according to depth, and no seasonal reproducibility was
      recorded from 1 year to the next. Our results showed that the bacterial community
      structure displayed lower diversity at 2 m (22 bands) compared to 50 m (32 bands)
      and that bacterial community structure dynamics followed dissimilar trends
      between the two depths. At 2 m, five shifts in the bacterial community structure
      occurred, with the temporal scale varying between 2 and 8 months whereas, at 50
      m, four shifts in the bacterial community structure took place at 50 m, with the
      temporal scale fluctuating between 3 and 13 months. More than 60% of the
      bacterial community structure variance was explained by seven variables at 2 m
      against eight at 50 m. Nutrients (PO(4)-P, NH(4)-N and NO(3)-N) and temperature
      were responsible for 49.6% of the variance at 2 m whereas these nutrients, with
      dissolved oxygen and chlorophyll a accounting for 59.6% of the variance at 50 m.
      Grazing by ciliates played also a critical role on the bacterial community
      structure at both depths. Our results suggest that the free-living bacterial
      community structure in the epi- and hypolimnion of Lake Bourget is mainly driven
      by combined, but differently weighted, top-down and bottom-up factors at 2 and 50
      m.

PMID- 21082180
TI  - Defining pseudoptosis (bottoming out) 3 years after short-scar medial pedicle
      breast reduction.
AB  - BACKGROUND: Pseudoptosis (bottoming out) is a well-observed phenomenon occurring
      after all types of breast reduction surgery. The authors' team previously
      reported the use of three-dimensional (3D) imaging to demonstrate that
      significant morphologic changes occur in the breast during the first year after
      short-scar medial pedicle breast reduction. This study extended this evaluation
      to postoperative year 3. METHODS: Patients undergoing short-scar medial pedicle
      breast reduction had 3D photographs taken using the Canfield Vectra 3-pod system
      or the Konica Minolta V910 during postoperative follow-up visits at 1 month, 1
      year, 2 years, and 3 years. Patients were assessed for pseudoptosis and breast
      morphologic changes using the 3D-based measurements. RESULTS: During the 3 year
      period, 10 patients completed the study. The total breast volume decreased
      significantly during the first postoperative year by 20.6% (P < 0.05). No change
      in volume occurred during postoperative years 2 and 3 (P > 0.05). Pseudoptosis
      was documented in the first postoperative year by a 6% migration of breast tissue
      from the upper pole to the lower pole of the breast (P < 0.05), without
      significant change noted during the next 2 postoperative years (P > 0.05). This
      redistribution of the breast parenchyma correlated with a decrease in breast
      anteroposterior projection of 10.6 mm (P < 0.05) during the same period, with an
      insignificant change during postoperative years 2 and 3. During the first
      postoperative year, 3D comparative analysis recorded a 4.4-mm difference in the
      3D topography (P < 0.05) and no further changes thereafter. The angle of breast
      projection showed a significant decrease of 17% (P < 0.05) in the first
      postoperative year and no change in subsequent years. CONCLUSION: Three
      dimensional photography is a useful tool enabling the plastic surgeon to monitor
      the postoperative changes in breast morphology objectively. This study provides
      quantifiable data demonstrating that pseudoptosis and tissue redistribution are
      limited to the initial postoperative year for patients undergoing short-scar
      medial pedicle breast reduction. The kinetic change in the breasts during
      postoperative years 2 and 3 appears to be minimal. Studies comparing the changes
      in morphology over time with different techniques of breast reduction are
      underway.

PMID- 21082179
TI  - Consensus structure of Pf1 filamentous bacteriophage from X-ray fibre diffraction
      and solid-state NMR.
AB  - Filamentous bacteriophages (filamentous bacterial viruses or Inovirus) are simple
      and well-characterised macromolecular assemblies that are widely used in
      molecular biology and biophysics, both as paradigms for studying basic biological
      questions and as practical tools in areas as diverse as immunology and solid
      state physics. The strains fd, M13 and f1 are virtually identical filamentous
      phages that infect bacteria expressing F-pili, and are sometimes grouped as the
      Ff phages. For historical reasons fd has often been used for structural studies,
      but M13 and f1 are more often used for biological experiments. Many other strains
      have been identified that are genetically quite distinct from Ff and yet have a
      similar molecular structure and life cycle. One of these, Pf1, gives the highest
      resolution X-ray fibre diffraction patterns known for filamentous bacteriophage.
      These diffraction patterns have been used in the past to derive a molecular model
      for the structure of the phage. Solid-state NMR experiments have been used in
      separate studies to derive a significantly different model of Pf1. Here we
      combine previously published X-ray fibre diffraction data and solid-state NMR
      data to give a consensus structure model for Pf1 filamentous bacteriophage, and
      we discuss the implications of this model for assembly of the phage at the
      bacterial membrane.

PMID- 21082181
TI  - Nasal strips for evaluating and classifying valvular nasal obstruction.
AB  - BACKGROUND: A normal-appearing upper lateral cartilage (ULC) or lower lateral
      cartilage (LLC) may be functionally abnormal. The Cottle sign estimates
      obstruction but not its exact location. A test is needed that evaluates the ULC
      and LLC separately. METHODS: The study included 30 patients with airway
      obstruction symptoms and signs referable only to the nasal valves. They received
      a Cottle test and a Breathe-Rite nasal strip to the middle third of the nose and
      again to the lower third (the rims). The patients were asked whether the strip
      made their inspiration better, worse, or no different and classified as BR 0 (no
      airway obstruction due to ULC/LLC dysfunction), BR I (improvement with the strip
      on the ULC), BR II (improvement with the strip on the LLC), or BR III
      (improvement with strips on both the ULC and the LLC, independently). All the
      patients underwent surgery involving spreader grafts, lateral crural struts,
      suture techniques, and the like. Correlations were sought between the BR
      classification, Cottle sign, and physical integrity of the ULC/LLC. RESULTS: A
      total of 12 patients required internal valve correction, whereas 8 required
      external valve correction, and 10 required correction of both. The Cottle test
      was nonspecific because most patients in all the groups exhibited a positive
      Cottle. However, the BR classification was specific, correlating with functional
      outcomes for 27 of the 30 patients. The McNemar test showed a significant
      correlation (Chi(2) = 9.09091; P = 0.00257) between physical finding and BR
      score. CONCLUSIONS: Inspiratory nasal function (related to ULC/LLC cartilages) is
      easily classified using nasal strips. The BR test is more specific and powerful
      than the Cottle test.

PMID- 21082182
TI  - Influence of mutagenesis of Bacillus thuringiensis Cry1Aa toxin on larvicidal
      activity.
AB  - Domain III of Bacillus thuringiensis Cry delta-endotoxins are considered to be
      related to the stability of the structure and avoidance of overdigestion by
      proteases. In this study, some residues of potential chymotrypsin and trypsin
      sites in Domain III of B. thuringiensis Cry1Aa were replaced individually with
      alanine by site-directed mutagenesis, in order to investigate their functional
      roles. Except F574A, all mutants F536A, R543A, F550A, F565A, R566A, F570A, F576A,
      F583A, and F590A were highly expressed the 130 kD protoxins at levels comparable
      to the wild-type tested by SDS-PAGE. In bioassays, F536A, R566A, and F590A
      increased toxicity against Spodoptera exigua Huner larve by 20, 40, and 40%,
      respectively, as compared to the wild-type. F536A and F565A showed an increase of
      6 and 10% in toxicity against Heliothis armigera Hubner than the wild-type.
      Toxicities of some mutants were altered greatly, and the same mutants were shown
      to have different toxicities against those two insects. Structural analyses
      showed that mutants R543A, F574A, F576A-affecting insecticidal activity might be
      relational to structural stability of toxin or decreased affinity for receptor
      binding. These results indicated that those residues were involved in the
      larvicidal activity of the Cry1Aa toxin.

PMID- 21082183
TI  - Expression of a barley cystatin gene in maize enhances resistance against
      phytophagous mites by altering their cysteine-proteases.
AB  - Phytocystatins are inhibitors of cysteine-proteases from plants putatively
      involved in plant defence based on their capability of inhibit heterologous
      enzymes. We have previously characterised the whole cystatin gene family members
      from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the
      effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae
      and Brevipalpus chilensis. The determination of proteolytic activity profile in
      both mite species showed the presence of the cysteine-proteases, putative targets
      of cystatins, among other enzymatic activities. All barley cystatins, except
      HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like
      activities, HvCPI-6 being the strongest inhibitor for both mite species.
      Transgenic maize plants expressing HvCPI-6 protein were generated and the
      functional integrity of the cystatin transgene was confirmed by in vitro
      inhibitory effect observed against T. urticae and B. chilensis protein extracts.
      Feeding experiments impaired on transgenic lines performed with T. urticae
      impaired mite development and reproductive performance. Besides, a significant
      reduction of cathepsin L-like and/or cathepsin B-like activities was observed
      when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These
      findings reveal the potential of barley cystatins as acaricide proteins to
      protect plants against two important mite pests.

PMID- 21082184
TI  - Heterothermy in the southern African hedgehog, Atelerix frontalis.
AB  - Most research on mammalian heterothermic responses in southern Africa tends to be
      laboratory based and biased towards rodents and smaller members of the
      Afrotheria. In this study, we continuously measured body temperature of southern
      African hedgehogs (Atelerix frontalis) between April and August 2009 (-10 degrees
      C < T (a) < 43 degrees C), kept under semi-captive conditions. A. frontalis
      showed a high propensity for torpor with animals spending up to 84% of the
      measurement period torpid. During this study, A. frontalis displayed the lowest T
      (b min) (ca 1 degrees C) yet recorded in an Afrotropical placental heterotherm.
      Bout lengths of between 0.7 h (40 min) and 116.3 h (4.8 days) were recorded.
      Differences in bout length were observed between lighter individuals compared
      with an individual exhibiting a higher body mass at the onset of winter, with low
      M (b) individuals exhibiting daily torpor whereas a heavier individual exhibited
      torpor bouts that were indicative of hibernation. Our results suggest that
      heterothermic responses are an important feature in the energy balance equation
      of this species and that body mass at the onset of winter may determine the
      patterns of heterothermy utilised in this species.

PMID- 21082185
TI  - Atrial-selective drugs for treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) is accompanied by a high risk of thromboembolic
      complications necessitating anticoagulation therapy. Arrhythmias have a high
      tendency to become persistent. Catheter ablation techniques are highly effective
      in the treatment of AF; however, these procedures are far too costly and time
      consuming for the routine treatment of large numbers of AF patients. Moreover,
      many patients prefer drug treatment although conventional antiarrhythmic drugs
      are moderately effective and are burdened with severe cardiac and noncardiac side
      effects. New antifibrillatory drugs developed for the treatment of AF include
      multichannel blockers with a high degree of atrial selectivity. The rationale of
      this approach is to induce antiarrhythmic actions only in the atria without
      conferring proarrhythmic effects in the ventricles.Atrial selective drug action
      is expected with ion channel blockers targeting ion channels that are expressed
      predominantly in the atria, i.e., Kv1.5 (I(Kur)), or Kir 3.1 and Kir 3.4
      (I(K,ACh)). Na(+) channel blockers that dissociate rapidly may exert atrial
      selectivity because of subtle differences in atrial and ventricular action
      potentials. Finally, atrial-selective targets may evolve due to disease-specific
      processes (e.g., rate-dependent Na(+) channel blockers, selective drugs against
      constitutively active I(K,ACh) channels).

PMID- 21082186
TI  - New emerging drugs targeting the genomic integrity and replication machinery in
      ovarian cancer.
AB  - INTRODUCTION: Ovarian cancer is a difficult to treat cancer entity with a high
      relapse rate. After initial surgery and chemotherapy, only a few options for
      therapeutic treatment remain in case of cancer recurrence. New treatment options
      with improved efficacies to circumvent acquired or pre-existing drug resistance
      are needed. MATERIALS: This survey focuses on new prospective drugs for ovarian
      cancer treatment that either cause direct damage to the nuclear DNA or inhibit
      chromosome segregation by acting as mitotic spindle inhibitors. RESULTS: Among a
      plethora of currently tested and proposed new drugs for ovarian cancer treatment,
      only a few appear to meet the criteria of sufficient and reliable efficacy with
      tolerable toxicity. These include the naturally occurring DNA-alkylating alkaloid
      trabectedin, the nitrogen mustard prodrug canfosfamide, and the synthetic kinase
      inhibitor ON-01910. The latter inhibits mitotic spindle formation without a
      direct tubulin interaction, avoiding adverse neurotoxic reactions common to the
      taxanes. Further, epothilones and oxaliplatin, already approved drugs for other
      cancer entities, show promising activity against ovarian cancer; they are even of
      interest as a first-line treatment option. DISCUSSION: Although the current focus
      and interest of modern cancer drug design tends to be more specific and targeted
      therapies, including therapeutic antibodies and specific small molecules to
      inhibit growth-, apoptosis-, and angiogenesis-regulating signalling cascades, the
      main target for ovarian cancer treatment appears to remain its basic, though
      uncontrolled working proliferation machinery. This includes the current gold
      standard for ovarian cancer chemotherapy, carboplatin, and taxanes, as well as
      the few remaining alternatives, such as topotecan, doxorubicin, and gemcitabine,
      which all rely on their ability to bind to or to modify the DNA or the chromosome
      separating spindle apparatus. Thus, the genomic integrity and replication
      machinery of ovarian cancer cells prove to represent an established, and
      obviously still effective target to be tackled for ovarian cancer treatment.

PMID- 21082187
TI  - Inhibin-betaA and -betaB subunits in normal and malignant glandular epithelium of
      uterine cervix and HeLa cervical cancer cell line.
AB  - INTRODUCTION: Inhibins, dimeric peptide hormones composed of an alpha-subunit and
      one of two possible beta-subunits (betaA or betaB), exhibit substantial roles in
      human reproduction and in endocrine-responsive tumors. However, it is still
      unclear if normal and cancerous cervical glandular epithelial cells as well as
      cervical cancer cell lines of glandular origin express the inhibin-betaA and 
      betaB subunits. MATERIALS AND METHODS: Normal cervical tissue samples and a total
      of 10 specimens of well-differentiated adenocarcinomas of the human cervix were
      analyzed for inhibin-betaA and -betaB subunit expression by immunohistochemical
      analysis. Additionally, the cervical carcinoma cell line HeLa was analyzed by
      immunofluorescence and RT-PCR analysis for the expression of inhibin subunits.
      RESULTS: Immunolabeling of normal and malignant glandular epithelium of human
      cervical tissue revealed a positive staining reaction for the inhibin-betaA and 
      betaB subunits. Additionally, the cancer cell line HeLa synthesized both inhibin
      subunits. When compared to the normal cervical glandular epithelium, the
      expression of the inhibin beta subunits became significantly reduced in cervical
      adenocarcinoma tissues. DISCUSSION: In conclusion, we demonstrated a strong,
      though differential expression pattern of inhibin-betaA and -betaB subunits in
      normal and malignant glandular epithelial cells of the human uterine cervix.
      Although the physiological role of inhibins is still quite unclear in cervical
      tissue, the expression of inhibin-beta-subunits might play an important role in
      cervical cancer carcinogenesis, since they are significantly down-regulated
      during pathogenesis in cervical adenocarcinomas.

PMID- 21082188
TI  - Postextubation obstructive pseudomembranes: a case series and review of a rare
      complication after endotracheal intubation.
AB  - Endotracheal intubation obviously may be life-saving, but it may also lead to
      complications, including those related to damage of the airways. Superficial
      damage of the trachea at the site of the endotracheal cuff may trigger the
      formation of an obstructive fibrinous tracheal pseudomembrane (OFTP). Shortly
      after extubation, this clot, consisting of fibrin, leucocytes, and necrotic
      epithelium, can cause stridor due to adherence to the tracheal wall and
      obstruction of the airway. In most cases, the lesion is easily removed by rigid
      or fiberoptic bronchoscopy and virtually never leads to permanent damage. The
      study consisted of case series and review of the literature. This report
      describes a series of five adult cases and reviews all 19 other previously
      described cases. A careful analysis of all reported cases, however, did not
      highlight a simple predisposing factor or illness. It is important to consider
      OFTP in the differential diagnosis of stridor and respiratory insufficiency in
      the postextubation period.

PMID- 21082189
TI  - Cyclododecane exposure in the field of conservation and restoration of art
      objects.
AB  - PURPOSE: Recent work practices in the conservation and restoration involve the
      use of cyclododecane (CDD, CAS 294-62-2) to protect fragile artifacts during
      their handling or transportation. Little is known about its toxicity, and no
      previous exposure has been reported. A short field investigation was conducted to
      characterize the exposure conditions to both CDD vapors and aerosols. METHODS:
      Measurements were conducted in the laboratory of conservation and restoration of
      the archeological service in Bern (Switzerland). Three indoor and four outdoor
      typical work situations, either during brush or spray gun applications, were
      investigated. Measurements were performed on charcoal adsorbent tube and analyzed
      by a gas chromatograph equipped with a flame ionization detector. RESULTS:
      Measurements have been conducted during both brush and spray gun applications.
      Indoor exposures were of 0.75-15.5 mg/m(3), while outdoors exposures were 19.5
      53.9 mg/m(3). Exposures appear to be extremely localized due to both
      physicochemical properties and application methods of the CDD. Vapor exposure
      increases dramatically with the confinement of the workplace. CONCLUSION:
      Preventive measures should be undertaken to limit as much as possible these
      exposures. Field work in confined areas (ditches, underground) is of particular
      concern. CDD-coated artifacts or materials should be stored in ventilated areas
      to avoid delayed exposures.

PMID- 21082190
TI  - Working conditions and psychosocial risk factors of employees in French
      electricity and gas company customer support departments.
AB  - OBJECTIVE: Little is known about the real impact of working conditions on the
      health of call center employees. The aim of this article is to describe the
      working conditions of French electricity and gas company customer service teams,
      especially those spending more than 75% of their working time handling calls in
      order to determine their subjective experience of their work and identify
      situations at risk of psychosocial constraints. METHODS: A cross-sectional study
      using a self-completion questionnaire was conducted on a representative sample of
      2,000 employees working in customer service centers. The questions focused on the
      variety of tasks performed, the organization of working time, the physical
      environment of the workstation, violent situations and psychosocial factors (Job
      Content Questionnaire). Multivariate statistical analyses were performed to
      identify factors associated with the wish to leave the sector and with a high
      level of psychosocial constraints. RESULTS: Women made up 66% of the sample.
      Despite a high educational level, the average socio-professional level of the
      employees was relatively low. Although the vast majority of employees had chosen
      this career (74%), just over half would like to leave. The main factors
      associated with iso-strain were inadequate breaks (odds ratio (OR) = 2.0), low
      perceived quality of work (OR = 2.4), high proportion of working time spent
      handling calls (>=75% of working time: OR = 5.9, between 50 and <75%: OR = 5.2),
      exposure to violence either internally (often or very often: OR = 3.1) or from
      customers (often or very often: OR = 1.8) and an unsatisfactory workplace (OR =
      2.0). CONCLUSIONS: Employees who spend more than 75% of their working time on the
      phone cumulate every factor linked with a high level of constraints, but all
      employees of the EDF and Gaz de France customer service centers are concerned.
      These workers share many characteristics with other call centers: predominantly
      female workforce; high educational level; wish to leave this sector despite the
      initial choice; high level of psychosocial risk factors.

PMID- 21082191
TI  - Bergen Burnout Inventory: reliability and validity among Finnish and Estonian
      managers.
AB  - OBJECTIVES: This study introduces a short measure for burnout (the Bergen Burnout
      Inventory, BBI) and examines its validity and reliability among managers in
      Finland and Estonia by means of confirmatory factor analysis. Burnout comprises
      three dimensions: (1) exhaustion at work (emotional component), (2) cynicism
      toward the meaning of work (cognitive component), and (3) the sense of inadequacy
      at work (behavioral component). METHODS: A total of 742 young Finnish managers
      and 414 Estonian managers responded to burnout (BBI) and effort-reward imbalance
      (ERI) scales. RESULTS: The results showed that the three-factor solution for
      burnout, compared to the one- or two-factor solutions, fitted the data best and
      gave the best reliability indices. The three theoretically derived dimensions of
      burnout were closely related but separate constructs. The BBI also had high item
      scale reliabilities among the managers in both countries. Finally, the effort
      reward imbalance (ERI) model and the three dimensions of burnout had similar
      associations among Finnish and Estonian managers providing evidence for the
      concurrent validity of the BBI. That is, high effort was related to high
      exhaustion and high cynicism. High reward was related to low exhaustion, but
      especially to low cynicism and low inadequacy. High overcommitment was related
      particularly to high exhaustion, but also to high cynicism and high inadequacy.
      CONCLUSIONS: The BBI can be used for the measurement of burnout in both research
      and occupational health contexts.

PMID- 21082192
TI  - Low prevalence of exercise-associated hyponatremia in male 100 km ultra-marathon
      runners in Switzerland.
AB  - We investigated the prevalence of exercise-associated hyponatremia (EAH) in 145
      male ultra-marathoners at the '100-km ultra-run' in Biel, Switzerland. Changes in
      body mass, urinary specific gravity, haemoglobin, haematocrit, plasma [Na(+)],
      and plasma volume were determined. Seven runners (4.8%) developed asymptomatic
      EAH. Body mass, haematocrit and haemoglobin decreased, plasma [Na(+)] remained
      unchanged and plasma volume increased. Delta body mass correlated with both post
      race plasma [Na(+)] and Delta plasma [Na(+)]. Delta plasma volume was associated
      with post race plasma [Na(+)]. The athletes consumed 0.65 (0.30) L/h; fluid
      intake correlated significantly and negatively (r = -0.50, p < 0.0001) to race
      time. Fluid intake was neither associated with post race plasma [Na(+)] nor with
      Delta plasma [Na(+)], but was related to Delta body mass. To conclude, the
      prevalence of EAH was low at ~5% in these male 100 km ultra-marathoners. EAH was
      asymptomatic and would not have been detected without the measurement of plasma
      [Na(+)].

PMID- 21082193
TI  - Atrophy of the lower limbs in elderly women: is it related to walking ability?
AB  - This study investigated the relationship between walking ability and age-related
      muscle atrophy of the lower limbs in elderly women. The subjects comprised 20
      young women and 37 elderly women who resided in nursing homes or chronic care
      institutions. The elderly subjects were divided into three groups according to
      their walking ability. The muscle thickness of the following ten lower limb
      muscles were measured by B-mode ultrasound: the gluteus maximus, gluteus medius,
      gluteus minimus, psoas major, rectus femoris, vastus lateralis, vastus
      intermedius, biceps femoris, gastrocnemius and soleus. Compared to the young
      group, muscle thicknesses of all muscles except the soleus muscle were
      significantly smaller in all the elderly groups. There were no significant
      differences between the fast- and slow-walking groups in the thickness of any
      muscle. In the dependent elderly group, noticeable muscle atrophy was observed in
      the quadriceps femoris muscle. The results of this study suggest that the elderly
      who are capable of locomotion, regardless of their walking speed, show a moderate
      degree of age-related atrophy, while those who do not walk exhibit more severe
      atrophy, especially in the quadriceps femoris muscle.

PMID- 21082194
TI  - Do marathon runners face an "ominous" risk of myocardial fibrosis?

PMID- 21082195
TI  - Pain and thermal sensation in the cold: the effect of interval versus continuous
      exercise.
AB  - Military and factory work often involves exposure to cold temperatures. With
      prolonged exposure, individuals report feeling cold and develop pain in their
      hands, both of which might be alleviated by endogenous heat production via
      exercise. The purpose of this study was to evaluate how interval (INT) and
      continuous (CONT) cycle ergometry alter thermal sensation, hand pain, mean finger
      temperature, and skin surface temperature gradient (forearm-finger) following
      immobility in moderate cold. Fourteen young men underwent two trials (each was
      three total hours in 5 degrees C) consisting of a 90-min period of acute cold
      exposure (ACE), 30 min of exercise (INT or CONT), and a 60-min recovery period
      (REC). INT and CONT were isoenergetic, reflecting 50 +/- 1% of each individual's
      VO(2) peak. All perceptual scales were significantly correlated during ACE (i.e.,
      test-retest reliability). As expected, individuals felt colder and reported more
      hand pain during ACE, as compared to thermoneutral conditions. Relative to ACE,
      both INT and CONT increased mean finger temperature, which was associated with
      warmer thermal sensation and less hand pain. During REC in 5 degrees C,
      individuals felt colder and reported more hand pain than during exercise.
      Although there were no perceptual differences between INT and CONT, moderate
      exercise in general can cause subjective feelings of warmth and less hand pain in
      people acutely exposed to moderate cold.

PMID- 21082196
TI  - Oxygen pretreatment as protection against decompression sickness in rats:
      pressure and time necessary for hypothesized denucleation and renucleation.
AB  - Pretreatment with HBO at 300-500 kPa for 20 min reduced the incidence of
      decompression sickness (DCS) in a rat model. We investigated whether this
      procedure would be effective with lower oxygen pressures and shorter exposure,
      and tried to determine how long the pretreatment would remain effective. Rats
      were pretreated with oxygen at 101 or 203 kPa for 20 min and 304 kPa for 5 or 10
      min. After pretreatment, the animals were exposed to air at 1,013 kPa for 33 min
      followed by fast decompression. Pretreatment at 101 or 203 kPa for 20 min and 304
      kPa for 10 min significantly reduced the number of rats with DCS to 45%, compared
      with 65% in the control group. However, after pretreatment at 304 kPa for 5 min,
      65% of rats suffered DCS. When pretreatment at 304 kPa for 20 min was followed by
      2 h in normobaric air before compression and decompression, the outcome was
      worse, with 70-90% of the animals suffering DCS. This is probably due to the
      activation of "dormant" micronuclei. The risk of DCS remained lower (43%) when
      pretreatment with 100% O(2) at normobaric pressure for 20 min was followed by a 2
      h interval in normobaric air (but not 6 or 24 h) before the hyperbaric exposure.
      The loss of effectiveness after a 6 or 24 h interval in normobaric air is related
      to micronuclei rejuvenation. Although pretreatment with hyperbaric O(2) may have
      an advantage over normobaric hyperoxia, decompression should not intervene
      between pretreatment and the dive.

PMID- 21082197
TI  - Sub-maximal and maximal Yo-Yo intermittent endurance test level 2: heart rate
      response, reproducibility and application to elite soccer.
AB  - The aims of this study were to (1) determine the reproducibility of sub-maximal
      and maximal versions of the Yo-Yo intermittent endurance test level 2 (Yo-Yo IE2
      test), (2) assess the relationship between the Yo-Yo IE2 test and match
      performance and (3) quantify the sensitivity of the Yo-Yo IE2 test to detect test
      retest changes and discriminate between performance for different playing
      standards and positions in elite soccer. Elite (n = 148) and sub-elite male (n =
      14) soccer players carried out the Yo-Yo IE2 test on several occasions over
      consecutive seasons. Test-retest coefficient of variation (CV) in Yo-Yo IE2 test
      performance and heart rate after 6 min were 3.9% (n = 37) and 1.4% (n = 32),
      respectively. Elite male senior and youth U19 players Yo-Yo IE2 performances were
      better (P < 0.01) than elite youth U16s and sub-elite players (2,603 +/- 451 and
      2,534 +/- 549 vs. 1,855 +/- 535 vs. 1,749 +/- 382 m). The intra- and inter-season
      CV for Yo-Yo IE2 test performance were 4.2 and 5.6%, respectively. A correlation
      was observed (P < 0.05) between Yo-Yo IE2 test performance and the total (r =
      0.74) and high-intensity (r = 0.58) running distance covered in a match. A
      correlation was also evident (P < 0.01) between Yo-Yo IE2 test heart rate after 6
      min expressed in percentage of maximal heart rate and the peak values for high
      intensity running performed by midfielders in 5-min (r = -0.71), 15-min (r = 
      0.75) and 45-min periods (r = -0.77). The present data demonstrate that the Yo-Yo
      IE2 test is reproducible and can be used to determine the capacity of elite
      soccer players to perform intense intermittent exercise. Furthermore, the Yo-Yo
      IE2 test was shown to be a sensitive tool that not only relates to match
      performance but can also differentiate between intermittent exercise performance
      of players in various standards, stages of the season and playing positions.

PMID- 21082198
TI  - VO2 underestimation using the Aquatrainer compared with facemask measurements: is
      it all in the ventilation?

PMID- 21082199
TI  - Applying double-magnetic induction to measure head-unrestrained gaze shifts:
      calibration and validation in monkey.
AB  - The double magnetic induction (DMI) method has successfully been used to record
      head-unrestrained gaze shifts in human subjects (Bremen et al., J Neurosci
      Methods 160:75-84, 2007a, J Neurophysiol, 98:3759-3769, 2007b). This method
      employs a small golden ring placed on the eye that, when positioned within
      oscillating magnetic fields, induces orientation-dependent voltages in a pickup
      coil in front of the eye. Here we develop and test a streamlined calibration
      routine for use with experimental animals, in particular, with monkeys. The
      calibration routine requires the animal solely to accurately follow visual
      targets presented at random locations in the visual field. Animals can readily
      learn this task. In addition, we use the fact that the pickup coil can be fixed
      rigidly and reproducibly on implants on the animal's skull. Therefore,
      accumulation of calibration data leads to increasing accuracy. As a first step,
      we simulated gaze shifts and the resulting DMI signals. Our simulations showed
      that the complex DMI signals can be effectively calibrated with the use of random
      target sequences, which elicit substantial decoupling of eye- and head
      orientations in a natural way. Subsequently, we tested our paradigm on three
      macaque monkeys. Our results show that the data for a successful calibration can
      be collected in a single recording session, in which the monkey makes about 1,500
      2,000 goal-directed saccades. We obtained a resolution of 30 arc minutes
      (measurement range [-60,+60] degrees ). This resolution compares to the fixation
      resolution of the monkey's oculomotor system, and to the standard scleral search
      coil method.

PMID- 21082200
TI  - Transcriptome analysis of hepatocytes after partial hepatectomy in rats.
AB  - After partial hepatectomy (PH), the recovery of liver mass is mainly mediated by
      proliferation and enlargement of hepatocytes. Therefore, measuring the
      transcriptional profiling of hepatocytes after PH will be helpful in exploring
      the mechanism of liver regeneration (LR). Firstly, hepatocytes were isolated from
      rat regenerating liver at different time points following PH, and then global
      gene expression analysis of hepatocytes was performed using Rat Genome 230 2.0
      Array. The results demonstrated that 1,417 genes in the array (including 767
      known genes) were identified to be LR-related. Clustering analysis demonstrated
      that 767 known genes fell into six classes with distinct expression kinetics.
      When gene expression patterns were combined with gene functions, genes involved
      in acute-phase response and defense response were rapidly elevated in early
      phases; those in cell proliferation and DNA replication were significantly up
      expressed in middle phase; a growing number of cell adhesion-involved genes were
      up-regulated as regeneration progressed; those in amino acid and lipid metabolism
      showed persistent down-regulation during LR. Based on the above analyses, it was
      suggested that hepatocyte defense mechanism was quickly triggered after PH; cell
      proliferation became active in middle phase; cell adhesion was strengthened in
      late phase; amino acid and lipid metabolism were attenuated during LR.
      Additionally, comparative analysis between transcriptional profiling of
      hepatocytes and regenerating liver indicated a major contribution of hepatocytes
      to LR.

PMID- 21082201
TI  - Expansion, diversification, and expression of T-box family genes in Porifera.
AB  - Sponges are among the earliest diverging lineage within the metazoan phyla.
      Although their adult morphology is distinctive, at several stages of development,
      they possess characteristics found in more complex animals. The T-box family of
      transcription factors is an evolutionarily ancient gene family known to be
      involved in the development of structures derived from all germ layers in the
      bilaterian animals. There is an incomplete understanding of the role that T-box
      transcription factors play in normal sponge development or whether developmental
      pathways using the T-box family share similarities between parazoan and
      eumetazoan animals. To address these questions, we present data that identify
      several important T-box genes in marine and freshwater sponges, place these genes
      in a phylogenetic context, and reveal patterns in how these genes are expressed
      in developing sponges. Phylogenetic analyses demonstrate that sponges have
      members of at least two of the five T-box subfamilies (Brachyury and Tbx2/3/4/5)
      and that the T-box genes expanded and diverged in the poriferan lineage. Our
      analysis of signature residues in the sponge T-box genes calls into question
      whether "true" Brachyury genes are found in the Porifera. Expression for a subset
      of the T-box genes was elucidated in larvae from the marine demosponge,
      Halichondria bowerbanki. Our results show that sponges regulate the timing and
      specificity of gene expression for T-box orthologs across larval developmental
      stages. In situ hybridization reveals distinct, yet sometimes overlapping
      expression of particular T-box genes in free-swimming larvae. Our results provide
      a comparative framework from which we can gain insights into the evolution of
      developmentally important pathways.

PMID- 21082202
TI  - Effect of rabeprazole treatment on health-related quality of life and symptoms in
      patients with reflux esophagitis: a prospective multicenter observational study
      in Japan.
AB  - BACKGROUND: Despite many reports from Western nations describing endoscopic and
      symptomatic improvements in patients with reflux esophagitis (RE) using proton
      pump inhibitors (PPI), PPI effects on the health-related quality of life (HRQOL),
      particularly for a dose duration of less than 8 weeks, have not been sufficiently
      clarified in Japanese RE patients. METHODS: RE patients (n = 9,029) in general
      practice settings took rabeprazole once daily for 8 weeks. HRQOL, using the 8
      item Short-Form Health Survey (SF-8TM), and symptoms, using a frequency scale for
      the symptoms of gastroesophageal reflux disease (GERD), were evaluated at the
      initiation of therapy (0 W), week 4 (4 W), and week 8 (8 W). Endoscopy was
      performed at 0 and 8 W where possible. RESULTS: In efficacy analysis (n = 6,839),
      the mean +/- SD values for the physical component summary of the SF-8TM at 0, 4,
      and 8 W were 45.005 +/- 7.534, 48.517 +/- 6.336, and 49.328 +/- 6.207,
      respectively, while those for the mental component summary were 46.465 +/- 7.743,
      49.460 +/- 6.470, and 50.388 +/- 6.049, respectively. Significant improvements,
      compared to 0 W, were observed in eight domains and two summary scores at 4 W (P
      < 0.001), and further QOL score elevations were seen by 8 W. Regarding symptoms,
      the mean total frequency scale for the symptoms of GERD (FSSG) scores at 0, 4,
      and 8 W were 16.4 +/- 9.8, 7.8 +/- 7.4, and 6.0 +/- 6.8, respectively.
      Significant improvements, compared to 0 W, were seen in the total, reflux, and
      dysmotility scores and in the scores for all 12 items at 4 W (P < 0.001).
      CONCLUSIONS: The score for the HRQOL of RE patients before rabeprazole therapy
      was below 50 points (the national mean for the general Japanese population),
      indicating harmed QOL. Rabeprazole markedly improved the HRQOL at 4 W, with
      recovery to the national mean by 8 W. Symptoms had also improved significantly at
      4 W, with further improvements observed at 8 W.

PMID- 21082203
TI  - Living with high putrescine: expression of ornithine and arginine biosynthetic
      pathway genes in high and low putrescine producing poplar cells.
AB  - Arginine (Arg) and ornithine (Orn), both derived from glutamate (Glu), are the
      primary substrates for polyamine (PA) biosynthesis, and also play important roles
      as substrates and intermediates of overall N metabolism in plants. Their cellular
      homeostasis is subject to multiple levels of regulation. Using reverse
      transcription quantitative PCR (RT-qPCR), we studied changes in the expression of
      all genes of the Orn/Arg biosynthetic pathway in response to up-regulation [via
      transgenic expression of mouse Orn decarboxylase (mODC)] of PA biosynthesis in
      poplar (Populus nigra * maximowiczii) cells grown in culture. Cloning and
      sequencing of poplar genes involved in the Orn/Arg biosynthetic pathway showed
      that they have high homology with similar genes in other plants. The expression
      of the genes of Orn, Arg and PA biosynthetic pathway fell into two hierarchical
      clusters; expression of one did not change in response to high putrescine, while
      members of the other cluster showed a shift in expression pattern during the 7
      day culture cycle. Gene expression of branch point enzymes (N-acetyl-Glu
      synthase, Orn aminotransferase, Arg decarboxylase, and spermidine synthase) in
      the sub-pathways, constituted a separate cluster from those involved in
      intermediary reactions of the pathway (N-acetyl-Glu kinase, N-acetyl-Glu-5-P
      reductase, N-acetyl-Orn aminotransferase, N (2)-acetylOrn:N-acetyl-Glu
      acetyltransferase, N (2)-acetyl-Orn deacetylase, Orn transcarbamylase,
      argininosuccinate synthase, carbamoylphosphate synthetase, argininosuccinate
      lyase, S-adenosylmethionine decarboxylase, spermine synthase). We postulate that
      expression of all genes of the Glu-Orn-Arg pathway is constitutively coordinated
      and is not influenced by the increase in flux rate through this pathway in
      response to increased utilization of Orn by mODC; thus the pathway involves
      mostly biochemical regulation rather than changes in gene expression. We further
      suggest that Orn itself plays a major role in the regulation of this pathway.

PMID- 21082204
TI  - A practical synthesis of N alpha-Fmoc protected L-threo-beta-hydroxyaspartic acid
      derivatives for coupling via alpha- or beta-carboxylic group.
AB  - A simple and practical general synthetic protocol towards orthogonally protected
      tHyAsp derivatives fully compatible with Fmoc solid-phase peptide synthetic
      methodology is reported. Our approach includes enantioresolution of commercially
      available D: ,L: -tHyAsp racemic mixture by co-crystallization with L: -Lys,
      followed by ion exchange chromatography yielding enantiomerically pure L: -tHyAsp
      and D: -tHyAsp, and their selective orthogonal protection. In this way N ( alpha
      )-Fmoc protected tHyAsp derivatives were prepared ready for couplings via either
      alpha- or beta-carboxylic group onto the resins or the growing peptide chain. In
      addition, coupling of tHyAsp via beta-carboxylic group onto amino resins allows
      preparation of peptides containing tHyAsn sequences, further increasing the
      synthetic utility of prepared tHyAsp derivatives.

PMID- 21082205
TI  - Determination of protein folding kinetic types using sequence and predicted
      secondary structure and solvent accessibility.
AB  - Proteins fold through a two-state (TS), with no visible intermediates, or a multi
      state (MS), via at least one intermediate, process. We analyze sequence-derived
      factors that determine folding types by introducing a novel sequence-based
      folding type predictor called FOKIT. This method implements a logistic regression
      model with six input features which hybridize information concerning amino acid
      composition and predicted secondary structure and solvent accessibility. FOKIT
      provides predictions with average Matthews correlation coefficient (MCC) between
      0.58 and 0.91 measured using out-of-sample tests on four benchmark datasets.
      These results are shown to be competitive or better than results of four modern
      predictors. We also show that FOKIT outperforms these methods when predicting
      chains that share low similarity with the chains used to build the model, which
      is an important advantage given the limited number of annotated chains. We
      demonstrate that inclusion of solvent accessibility helps in discrimination of
      the folding kinetic types and that three of the features constitute statistically
      significant markers that differentiate TS and MS folders. We found that the
      increased content of exposed Trp and buried Leu are indicative of the MS folding,
      which implies that the exposure/burial of certain hydrophobic residues may play
      important role in the formation of the folding intermediates. Our conclusions are
      supported by two case studies.

PMID- 21082206
TI  - Omentin inhibits osteoblastic differentiation of calcifying vascular smooth
      muscle cells through the PI3K/Akt pathway.
AB  - Arterial calcification is positively associated with visceral adiposity, but the
      mechanisms remain unclear. Omentin is a novel adipokine that is selectively
      expressed in visceral adipose tissue. The levels of circulating omentin are
      decreased in obesity, and they correlate negatively with waist circumference.
      This study investigated the effects of omentin on the osteoblastic
      differentiation of calcifying vascular smooth muscle cells (CVSMCs), a
      subpopulation of aortic smooth muscle cells putatively involved in vascular
      calcification. Omentin inhibited mRNA expression of alkaline phosphatase (ALP)
      and osteocalcin; omentin also suppressed ALP activity, osteocalcin protein
      production, and the matrix mineralization. Furthermore, omentin selectively
      activated phosphatidylinositol 3-kinase (PI3K) downstream effector Akt. Moreover,
      inhibition of PI3K or Akt activation reversed the effects of omentin on ALP
      activity and the matrix mineralization. The present results demonstrate for the
      first time that omentin can inhibit osteoblastic differentiation of CVSMCs via
      PI3K/Akt signaling pathway, suggesting that the lower omentin levels in obese
      (specially visceral obese) subjects contribute to the development of arterial
      calcification, and omentin plays a protective role against arterial
      calcification.

PMID- 21082207
TI  - Prediction of a new class of RNA recognition motif.
AB  - The observation that activation domains (AD) of procarboxypeptidases are rather
      long compared to the pro-regions of other zymogens raises the possibility that
      they could play additional roles apart from precluding enzymatic activity within
      the proenzyme and helping in its folding process. In the present work, we
      compared the overall pro-domain tertiary structure with several proteins
      belonging to the same fold in the structural classification of proteins (SCOP)
      database by using structure and sequence comparisons. The best score obtained was
      between the activation domain of human procarboxypeptidase A4 (ADA4h) and the
      human U1A protein from the U1 snRNP. Structural alignment revealed the existence
      of RNP1- and RNP2-related sequences in ADA4h. After modeling ADA4h on U1A, the
      new structure was used to extract a new sequence pattern characteristic for
      important residues at key positions. The new sequence pattern allowed scanning
      protein sequences to predict the RNA-binding function for 32 sequences undetected
      by PFAM. Unspecific RNA electrophoretic mobility shift assays experimentally
      supported the prediction that ADA4h binds an RNA motif similar to the U1A binding
      motif of stem-loop II of U1 small nuclear RNA. The experiments carried out with
      ADA4h in the present work suggest the sharing of a common ancestor with other RNA
      recognition motifs. However, the fact that key residues preventing activity
      within the proenzyme are also key residues for RNA binding might have induced the
      activation domains of procarboxypeptidases to evolve from the canonical RNP1 and
      RNP2 sequences.

PMID- 21082209
TI  - Serodiagnosis of Mycobacterium avium-complex pulmonary disease with an enzyme
      immunoassay kit that detects anti-glycopeptidolipid core antigen IgA antibodies
      in patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) has many pulmonary manifestations, including bronchial
      abnormalities that can develop into Mycobacterium avium-complex (MAC) pulmonary
      disease (PD). MAC-PD can be lethal in patients receiving tumor necrosis factor
      alpha blockers despite administration of antibiotics. Diagnosis of MAC-PD is
      often difficult, because MAC is an environmental organism. In this study, we
      investigated the usefulness of serodiagnosis of MAC-PD in RA patients by using an
      enzyme immunoassay (EIA) kit that detects anti-glycopeptidolipid (GPL) core
      antigen IgA antibodies. Antibody levels were measured in 63 patients with RA: 14
      with MAC-PD plus 3 cultured nontuberculous mycobacteria (NTM) other than MAC, 16
      with pulmonary abnormalities characterizing NTM but undetected in sputum culture,
      and 30 control subjects. RA patients with MAC-PD showed significantly higher
      antibody levels than controls (p = 0.02). The cutoff point was set at 0.7 IU/l,
      making the sensitivity and specificity of the antibody in MAC-PD and control
      patients 43% and 100%, respectively. The EIA kit is useful for diagnosis of MAC
      PD in RA patients because of its high specificity. This test is an easier and
      less invasive form of examination and could therefore replace bronchoscopy as the
      main diagnostic procedure for RA patients with MAC-PD.

PMID- 21082208
TI  - Laparoscopic ventral/incisional hernia repair: a single centre experience of
      1,242 patients over a period of 13 years.
AB  - BACKGROUND AND PURPOSE: Laparoscopic technique is now well established for
      ventral/incisional hernia repair. However several issues such as optimal fixation
      technique, occult hernias, management of inadvertent enterotomies, postoperative
      seromas and recurrence require appraisal. METHODS: A single centre retrospective
      review of 1,242 patients between January 1992 and June 2005 is described. All
      patients had laparoscopic ventral/incisional hernia repair (LVIHR) following a
      standardised protocol by five consultants and fellows in a dedicated minimal
      access surgery unit of a tertiary care hospital. RESULTS: LVIHR was completed in
      1,223 patients (98.5%). The average BMI was 32, mean defect size was 26.2 cm(2),
      mean operating time was 81 min and mean hospital stay was 1.9 days. The mean mesh
      to hernia ratio was 37.5. Occult hernias were observed in 203 (16.3%) patients
      and inadvertent enterotomies occurred in 21 (1.7%) patients. Mortality occurred
      in two patients, pulmonary embolism and cardiac dysrhythmia being the respective
      reasons. The most common sequel was early seroma formation (25%). Chronic pain
      occurred in 14.7% patients. Recurrence rate was 4.4%, which was associated with a
      higher BMI, use of staplers as fixation device, multiple defects and recurrent
      hernias. The mean follow up was 5.4 years; (range 2.4-10 years). The follow up
      rate was 78%. CONCLUSION: LVIHR leads to low recurrence rates and low rates of
      wound and mesh infection. Occult hernias are diagnosed and optimally treated
      laparoscopically. However, chronic pain remains an unresolved issue.

PMID- 21082210
TI  - Mechanics and remodelling of cell packings in epithelia.
AB  - Epithelia are sheets of cells that are dynamically remodelled by cell division
      and cell death during development. Here we describe the cell shapes and packings
      as networks of polygons: stable and stationary network configurations obey force
      balance and are represented as local minima of a potential function. We
      characterize the physical properties of this vertex model, including the set of
      ground states, and the energetics of topological rearrangements. We furthermore
      discuss a quasistatic description of cell division that allows us to study the
      mechanics and dynamics of tissue remodelling during growth. The biophysics of
      cells and their rearrangements can account for the morphology of cell packings
      observed in experiments.

PMID- 21082211
TI  - Modeling of Fusarium redolens Dzf2 mycelial growth kinetics and optimal fed-batch
      fermentation for beauvericin production.
AB  - Beauvericin (BEA) is a cyclic hexadepsipeptide mycotoxin with notable phytotoxic
      and insecticidal activities. Fusarium redolens Dzf2 is a highly BEA-producing
      fungus isolated from a medicinal plant. The aim of the current study was to
      develop a simple and valid kinetic model for F. redolens Dzf2 mycelial growth and
      the optimal fed-batch operation for efficient BEA production. A modified Monod
      model with substrate (glucose) and product (BEA) inhibition was constructed based
      on the culture characteristics of F. redolens Dzf2 mycelia in a liquid medium.
      Model parameters were derived by simulation of the experimental data from batch
      culture. The model fitted closely with the experimental data over 20-50 g l(-1)
      glucose concentration range in batch fermentation. The kinetic model together
      with the stoichiometric relationships for biomass, substrate and product was
      applied to predict the optimal feeding scheme for fed-batch fermentation, leading
      to 54% higher BEA yield (299 mg l(-1)) than in the batch culture (194 mg l(-1)).
      The modified Monod model incorporating substrate and product inhibition was
      proven adequate for describing the growth kinetics of F. redolens Dzf2 mycelial
      culture at suitable but not excessive initial glucose levels in batch and fed
      batch cultures.

PMID- 21082212
TI  - Effect of temperature on D-arabitol production from lactose by Kluyveromyces
      lactis.
AB  - D-arabitol production from lactose by Kluyveromyces lactis NBRC 1903 has been
      studied by following the time courses of concentrations of cell mass, lactose, D:
      -arabitol, ethanol, and glycerol at different temperatures. It was found that
      temperature is a key factor in D-arabitol production. Within temperatures ranging
      from 25 to 39 degrees C, the highest D-arabitol concentration of 99.2 mmol l(-1)
      was obtained from 555 mmol l(-1) of lactose after 120 h of batch cultivation at
      37 degrees C. The yield of D-arabitol production on cell mass growth increased
      drastically at temperatures higher than 35 degrees C, and the yield reached 1.07
      at 39 degrees C. Increasing the cell mass concentration two-fold after 24 h of
      culture growth at 37 degrees C, the D-arabitol concentration further increased to
      168 mmol l(-1). According to the distribution of the metabolic products,
      metabolic changes related to growth phase were also discussed. The stationary
      phase K. lactis cells in the batch culture that is started with exposing the
      precultured inoculum to high osmotic stress, high oxidative stress, and high heat
      stress are found to be preferable for D-arabitol production.

PMID- 21082213
TI  - Visualizing space, time, and agents: production, performance, and preference.
AB  - Visualizations of space, time, and agents (or objects) are ubiquitous in science,
      business, and everyday life, from weather maps to scheduling meetings. Effective
      communications, including visual ones, emerge from use in the field, but no
      conventional visualization form has yet emerged for this confluence of
      information. The real-world spiral of production, comprehension, and use that
      fine-tunes communications can be accelerated in the laboratory. Here, we do so in
      search of effective visualizations of space, time, and agents. Users' production,
      preference, and performance aligned to favor matrix representations with time as
      rows or columns and space and agents as entries. Overall, performance and
      preference were greater for matrices with discrete dots representing cell entries
      than for matrices with lines, but lines connecting cells may provide an advantage
      when evaluating temporal sequence. Both the diagram type and the technique have
      broader applications.

PMID- 21082215
TI  - Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na+/H+
      exchange inhibition: Gumina, NHE-1 inhibition and platelet aggregation.
AB  - BIIB 513 and EMD 85131 are selective inhibitors of the Na+/H+ exchanger-1 (NHE-1)
      that are benzoylguanidine derivatives of the clinically employed diuretic
      amiloride. Prior studies have suggested a role for NHE-1 activity in platelet
      activation and aggregation using amiloride or its non- benzoylguanidines
      derivatives. However, the concentrations employed in these prior studies were at
      levels known to exert effects on other ion transport systems besides the NHE-1.
      Therefore, the purpose of this study was to examine the effects of more selective
      NHE-1 inhibitors, BIIB 513 and EMD 85131, on platelet aggregation and in vivo
      cyclic flow following arterial injury. BIIB 513 and EMD 85131 effects on ex vivo
      canine and human platelet aggregation in response to various agents was monitored
      via platelet aggregation. For analysis of in vivo thrombus formation, a femoral
      artery crush injury model was employed and a flow meter was used to monitor the
      effect of BIIB 513 on cyclic blood flow. Treatment of either canine or human
      platelets with up to 1 mM of BIIB 513 had no effect on aggregation induced by
      platelet activating factor (PAF), thrombin receptor activator peptide (TRAP), or
      adenosine diphosphate (ADP). Additionally, the structurally related compound EMD
      85131 at up to 1 mM failed to inhibit TRAP induced platelet aggregation. In vivo
      administration of up to 9 mg/kg of BIIB 513 intravenously failed to affect cyclic
      flow in a canine model of femoral artery injury. These data demonstrate that the
      specific and selective NHE-1 inhibitors BIIB 513 or EMD 85131 have no effect on
      ex vivo platelet aggregation or in vivo cyclic flow following arterial injury.

PMID- 21082214
TI  - The elephant in the room: do microRNA-based therapies have a realistic chance of
      succeeding for brain tumors such as glioblastoma?
AB  - It seems quite clear that microRNAs play important roles in neuro-oncology, as
      they do across perhaps all areas in biology. With recent advances in detecting
      and quantifying microRNAs in tissue and serum, it appears increasingly likely
      that microRNAs will be clinically useful as biomarkers for brain tumors and other
      cancers. Applying microRNAs for treatment of brain tumors poses greater hurdles
      by far, however, and despite promising in vitro results this may never become a
      reality. This review fits recent advances into a framework for considering the
      potential of microRNAs for brain tumor therapy, considering the power of
      individual microRNAs, delivery issues, and indirect microRNA-based therapies.

PMID- 21082216
TI  - Preface: a special issue on mine reclamation and suitable management for heavy
      metals.

PMID- 21082217
TI  - Carbamazepine promotes Her-2 protein degradation in breast cancer cells by
      modulating HDAC6 activity and acetylation of Hsp90.
AB  - Histone deacetylase 6 (HDAC6) inhibition, recently, has been shown to promote the
      acetylation of heat-shock protein 90 (Hsp90) and disrupt its chaperone function.
      Her-2 oncoprotein is identified as a client protein of Hsp90. Therefore, in this
      study we examined the effect of carbamazepine, which could inhibit HDAC on Hsp90
      acetylation and Her-2 stability. The results of this study demonstrate that while
      carbamazepine had no effect on the Her-2 mRNA level, it induced Her-2 protein
      degradation via the proteasome pathway by disrupting the chaperone function of
      Hsp90 in SK-BR-3 cells. Mechanistically, carbamazepine could enhance the
      acetylation of alpha-tubulin, indicating its inhibitory effect on HDAC6.
      Functionally, carbamazepine could synergize with trastuzumab or geldanamycin to
      promote Her-2 degradation and inhibit breast cancer cell proliferation. Thus,
      this study has potential clinical implications by providing a promising strategy
      to overcome the development of resistance against trastuzumab therapy for breast
      cancer.

PMID- 21082219
TI  - The riddle of sex: biological theories of sexual difference in the early
      twentieth-century.
AB  - At the turn of the twentieth century, biologists such as Oscar Riddle, Thomas
      Hunt Morgan, Frank Lillie, and Richard Goldschmidt all puzzled over the question
      of sexual difference, the distinction between male and female. They all offered
      competing explanations for the biological cause of this difference, and engaged
      in a fierce debate over the primacy of their respective theories. Riddle
      propounded a metabolic theory of sex dating from the late-nineteenth century
      suggesting that metabolism lay at the heart of sexual difference. Thomas Hunt
      Morgan insisted on the priority of chromosomes, Frank Lillie emphasized the
      importance of hormones, while Richard Goldschmidt supported a mixed model
      involving both chromosomes and hormones. In this paper, I will illustrate how the
      older metabolic theory of sex was displaced when those who argued for the
      relatively newer theories of chromosomes and hormones gradually formed an
      alliance that accommodated each other and excluded the metabolic theory of sex.
      By doing so, proponents of chromosomes and hormones established their authority
      over the question of sexual difference as they laid the foundations for the new
      disciplines of genetics and endocrinology. Their debate raised urgent questions
      about what constituted sexual difference, and how scientists envisioned the
      plasticity and controllability of this difference. These theories also had
      immediate political and cultural consequences at the turn of the twentieth
      century, especially for the eugenic and feminist movements, both of which were
      heavily invested in knowledge of sex and its determination, ascertainment, and
      command.

PMID- 21082218
TI  - Autophagic-lysosomal pathway functions in the masseter and tongue muscles in the
      klotho mouse, a mouse model for aging.
AB  - Klotho mutant (kl/kl) mice, a type of short-lived mouse models, display several
      aging-related phenotypes. To investigate whether the atrophy of skeletal muscles
      is induced in these mice via activation of the ubiquitin-proteasomal pathway
      and/or the autophagic-lysosomal pathway through an alteration of insulin/IGF-I
      signaling, we analyzed the activity of the two pathways for protein degradation
      and components of the insulin/IGF signaling pathway in their skeletal muscles.
      The masseter, tongue, and gastrocnemius muscles in kl/kl showed marked reductions
      in muscle weight and in myofiber diameter compared with +/+. The autophagic
      lysosomal pathway in kl/kl was activated in the masseter and tongue, but not in
      the gastrocnemius, compared with that in +/+, whereas the ubiquitin-proteasomal
      pathway in these three muscles of kl/kl was not altered. No marked difference in
      the phosphorylation levels of insulin/IGF-I signaling components, such as
      insulin/IGF-I receptor, Akt, and FoxO in three muscles studied were found between
      kl/kl and +/+, but the phosphorylation levels of signaling component at the
      downstream of mTOR such as 4E-BP1 and p70 S6K were suppressed in the masseter and
      tongue of kl/kl compared with +/+. Deficiency of essential amino acids is
      reported to activate the autophagy-lysosomal pathway through the down-regulation
      of mTOR, not through IGF-Akt-FoxO. The masseter and tongue seem to be more
      actively moved than limb muscles in kl/kl, because they are essential for
      survival activities such as mastication, swallowing, and respiration. Thus, the
      deficiency of amino acid by the active movement of the masseter and tongue seems
      to stimulate the autophagic-lysosomal pathway via the down-regulation of mTOR
      signalling pathway.

PMID- 21082220
TI  - Molecular interaction fields (MIFs) to predict lipophilicity and ADME profile of
      antitumor Pt(II) complexes.
AB  - PURPOSE: To describe a computational tool to calculate molecular descriptors of
      potential application in ADME virtual screening of antitumor Pt(II) drug
      candidates. METHODS: The multistep computational procedure consists in (a)
      building and optimization (PM3) of the 3D structures of the investigated
      complexes, (b) parametrization of Pt(II) and its implementation in GRID, (c) GRID
      calculations and extraction of the information content with VolSurf and
      BIOCUBE4mf, and (d) PLS analysis to look for the correlation between experimental
      data and the molecular descriptors. RESULTS: The following results were obtained:
      (a) the calibration of the GRID force field to take into account the platinum di
      cation, (b) solid PLS models between log k30 and log kw with VolSurf descriptors
      which highlight the main structural differences between the two chromatographic
      parameters, (c) the prediction of virtual (of each conformer) log k30 and log kw,
      and (d) the identification of the main descriptors governing VD(ss) of drugs in
      clinical use. CONCLUSION: The study suggests a strategy to identify good Pt(II)
      complexes prior to their synthesis to eliminate as soon as possible drug
      candidates with unfavorable PK profile.

PMID- 21082221
TI  - Microneedles for drug delivery.

PMID- 21082222
TI  - Classification of benign and malignant breast masses based on shape and texture
      features in sonography images.
AB  - The purpose of this research was evaluating novel shape and texture feature'
      efficiency in classification of benign and malignant breast masses in sonography
      images. First, mass regions were extracted from the region of interest (ROI) sub
      image by implementing a new hybrid segmentation approach based on level set
      algorithms. Then two left and right side areas of the masses are elicited. After
      that, six features (Eccentricity_feature, Solidity_feature,
      DeferenceArea_Hull_Rectangular, DeferenceArea_Mass_Rectangular, Cross-correlation
      left and Cross-correlation-right) based on shape, texture and region
      characteristics of the masses were extracted for further classification. Finally
      a support vector machine (SVM) classifier was utilized to classify breast masses.
      The leave-one-case-out protocol was utilized on a database of eighty
      pathologically-proven breast sonographic images of patients (forty-seven benign
      cases and thirty-three malignant cases) to evaluate our method. The
      classification results showed an overall accuracy of 95.00%, sensitivity of
      90.91%, specificity of 97.87%, positive predictive value of 96.77%, negative
      predictive value of 93.88%, and Matthew's correlation coefficient of 89.71%. The
      experimental results declare that our proposed method is actually a beneficial
      tool for the diagnosis of the breast cancer and can provide a second opinion for
      a physician's decision or can be used for the medicine training especially when
      coupled with other modalities.

PMID- 21082223
TI  - How do changes in exhaled CO2 measure changes in cardiac output? A numerical
      analysis model.
AB  - OBJECTIVE: In a previous study in anesthetized animals, the slope of percent
      decreases in exhaled CO2 versus percent decreases in cardiac output (Q(T)
      inflation of vena cava balloons) was 0.73. To examine the mechanisms underlying
      this exhaled CO2-Q(T) relationship, an iterative numerical analysis computer
      model of non-steady state CO(2) kinetics was developed. METHODS: The model
      consisted of a large peripheral tissue compartment connected by venous return and
      [Formula: see text] to a small central pulmonary compartment. Equations were
      developed to describe the movement of CO2 in this system. Decreases in Q(T) were
      accompanied by experimentally measured increases in alveolar dead space fraction
      (VD: (alv)/VT: (alv)), generated by decreased pulmonary vascular pressure during
      the Q(T) decrease. RESULTS: When the model was perturbed by a 40% decrease in
      Q(T) and an increase in VD: (alv)/VT: (alv) from 5 to 20.6%, average alveolar
      expired P(CO2) (PAE(CO2)) decreased from 37.5 to 29.4 mm Hg, similar to the
      animal experiments. Due to the high peripheral tissue compliance for CO2, the
      computer model demonstrated that, after a decrease in Q(T), at least 1 h was
      required for compartment CO2 stores to approach a new equilibrium state.
      CONCLUSIONS: The numerical analysis computer model helps to delineate the
      mechanisms underlying how decreased Q(T) resulted in decreased exhaled CO2. The
      model permitted deconvolution of the effects of simultaneous variables and the
      interrogation of parameters that would be difficult to measure in actual
      experiments.

PMID- 21082224
TI  - CTLA-4, position 49 A/G polymorphism associated with coronary artery lesions in
      Kawasaki disease.
AB  - OBJECTIVE: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and
      primarily affects children less than 5 years of age. Cytotoxic T lymphocyte
      associated antigen-4 (CTLA-4) has been suggested as a candidate gene for
      conferring susceptibility to autoimmunity. This study examined the correlation of
      CTLA-4 gene polymorphisms in KD with and without coronary artery lesions (CAL).
      MATERIALS AND METHODS: A total of 233 KD patients and 644 controls were subjected
      to determination of CTLA-4 polymorphisms at (-318) C/T and (+49) A/G positions by
      restriction fragment length polymorphism. Susceptibility, CAL, and intravenous
      immunoglobulin treatment response of KD were then analyzed with genetic variants.
      RESULTS: Polymorphisms of CTLA-4 (+49 A/G) and (-318 C/T) were not significantly
      different between normal children and patients with KD. The CTLA-4 (+49) A allele
      (AA+AG genotype), however, was significantly associated with CAL formation,
      especially in female patients. CONCLUSIONS: This study provides the first
      evidence supporting the association of CTLA-4 (+49) A/G polymorphism with the CAL
      formation of KD particularly in female patients.

PMID- 21082225
TI  - The -308 G/A polymorphism in TNF-alpha gene is associated with asthma risk: an
      update by meta-analysis.
AB  - BACKGROUND: The -308 G/A polymorphism in TNF-alpha gene has been extensively
      investigated for association to asthma; however, results of different studies
      have been inconsistent. The aim of this study is to comprehensively evaluate the
      genetic risk of -308 G/A polymorphism in TNF-alpha gene for asthma. METHODS: A
      meta-analysis was carried out to analyze the association between the -308 G/A
      polymorphism TNF-alpha gene and asthma risk. RESULTS: A total of 4717 cases and
      5012 controls in 29 case-control studies were included in this meta-analysis. The
      result indicated that the variant A allele carriers had a 38% increased risk of
      asthma, when compared with the homozygote GG (odds ratio (OR) = 1.40, 95%
      confidence interval (CI), 1.13-1.68 for AA + AG vs. GG). In the subgroup analysis
      by ethnicity, significant elevated risks were associated with A allele carriers
      in Asians (OR = 1.53, 95% CI = 1.17-2.01 and P = 0.002) but not in Caucasians(OR
      = 1.06, 95% CI = 0.75-1.50 and P = 0.73). In the subgroup analysis by age,
      significant elevated risks were associated with A allele carriers in adults (OR =
      1.44, 95% CI = 1.14-1.81, and P = 0.002) and children (OR = 1.37, 95% CI = 1.03
      1.82, and P = 0.003). In the subgroup analysis by atopic status, significant
      elevated risks of asthma were associated with A allele carriers in atopic
      population (OR = 1.68, 95% CI = 1.34-2.10, and P < 0.00001) but not in non-atopic
      population (OR = 0.98, 95% CI = 0.58-1.68, and P = 0.95). CONCLUSIONS: Our
      results suggest that the TNF-alpha -308 G/A polymorphism contributes to
      susceptibility to asthma.

PMID- 21082226
TI  - Purification, biochemical characterization, and cloning of phospholipase D from
      Streptomyces racemochromogenes strain 10-3.
AB  - We previously isolated Streptomyces racemochromogenes strain 10-3, which produces
      a phospholipase D (PLD) with high transphosphatidylation activity. Here, we
      purified and cloned the PLD (PLD103) from the strain. PLD103 exerted the highest
      hydrolytic activity at a slightly alkaline pH, which is in contrast to the
      majority of known Streptomyces PLDs that have a slightly acidic optimum pH.
      PLD103 shares only 71-76% amino acid sequence identity with other Streptomyces
      PLDs that have a slightly acidic optimum pH; thus, the diversity in the primary
      structure might explain the discrepancy observed in the optimum pH. The purified
      PLD displayed high transphosphatidylation activity in the presence of glycerol,
      L: -serine, and 2-aminoethanol hydrochloride with a conversion rate of 82-97% in
      a simple one-phase system, which was comparable to the rate of other Streptomyces
      PLDs in a complicated biphasic system.

PMID- 21082227
TI  - Oxidized NADH oxidase inhibits activity of an ATP/NAD kinase from a Thermophilic
      archaeon.
AB  - NADH oxidases (NOXs) are important enzymes in detoxifying oxidative stress and
      regenerating oxidized pyridine nucleotides. In the present study, a NOX from
      Thermococcus kodakarensis KOD1 (NOXtk) was recombinantly expressed in Escherichia
      coli and purified to homogeneity. NOXtk displayed NADH oxidase activity that was
      inhibited by oxidization. Under physiological conditions, unoxidized and oxidized
      NOXtk formed dimers and hexamers, respectively. Mutating the single cysteine
      residue Cys45 to alanine (NOXtkC45A) decreased NADH oxidase activity without
      affecting dimerization or hexamerization, suggesting that oligomerization does
      not occur through disulfide bond formation. Pull-down assay results indicated
      that an ATP/NAD kinase from T. kodakarensis KOD1 (ANKtk) binds to NOXtk. Use of
      several assays revealed that ANKtk can only bind to oxidized hexameric NOXtk,
      through which it inhibits ANKtk activity. Because ANKtk converts NADH to NADPH
      (an important factor in oxidative stress protection), a model based on in vitro
      result was proposed in which NOXtk hexamerization under oxic conditions inhibits
      both NOXtk and ANKtk activities, thereby sensitizing cells to oxidative stress
      induced death.

PMID- 21082228
TI  - Functioning of the mitochondrial ATP-dependent potassium channel in rats varying
      in their resistance to hypoxia. Involvement of the channel in the process of
      animal's adaptation to hypoxia.
AB  - The mechanism of tissue protection from ischemic damage by activation of the
      mitochondrial ATP-dependent K(+) channel (mitoK(ATP)) remains unexplored. In this
      work, we have measured, using various approaches, the ATP-dependent mitochondrial
      K(+) transport in rats that differed in their resistance to hypoxia. The
      transport was found to be faster in the hypoxia-resistant rats as compared to
      that in the hypoxia-sensitive animals. Adaptation of animals to the intermittent
      normobaric hypoxia increased the rate of transport. At the same time, the
      intramitochondrial concentration of K(+) in the hypoxia-sensitive rats was higher
      than that in the resistant and adapted animals. This indicates that adaptation to
      hypoxia stimulates not only the influx of potassium into mitochondria, but also
      K(+)/H(+) exchange. When mitoK(ATP) was blocked, the rate of the mitochondrial
      H(2)O(2) production was found to be significantly higher in the hypoxia-resistant
      rats than that in the hypoxia-sensitive animals. The natural flavonoid-containing
      adaptogen Extralife, which has an evident antihypoxic effect, increased the rate
      of the mitochondrial ATP-dependent K(+) transport in vitro and increased the in
      vivo tolerance of hypoxia-sensitive rats to acute hypoxia 5-fold. The involvement
      of the mitochondrial K(+) transport in the mechanism of cell adaptation to
      hypoxia is discussed.

PMID- 21082229
TI  - Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A): overview
      and design.
AB  - This article presents an overview of the Finnish Prenatal Study of Autism and
      Autism Spectrum Disorders (FIPS-A), a new study designed to examine the
      relationship between prenatal serologic factors, mediating and moderating
      developmental antecedents, and risk of autism spectrum disorders (ASD). The FIPS
      A is based on register linkages between births from 1987 to 2005 ascertained from
      the Finnish Medical Birth Register (FMBR) and other national registers on
      treatment for this group of disorders. All subjects were members of the Finnish
      Maternity Cohort (FMC), which consists of virtually all births in Finland from
      1983 to the present, and which includes archived maternal serum samples. This
      study also capitalizes on other registry information, such as systematically
      collected data on pregnancy, prenatal and neonatal complications and manual data
      collection from well-child clinics providing developmental data from birth to the
      age of 7 years. In this paper, we describe the methods used in the FIPS-A study,
      including a description of the national registers, available data and case
      ascertainment procedures. Finally, we discuss implications of the data for future
      work on uncovering putative aetiologies of ASD and key strengths and limitations
      of the design.

PMID- 21082231
TI  - Characterisation of potato virus Y isolates from Iran.
AB  - A survey of Potato virus Y (PVY) was conducted in cultivated fields in six
      Iranian provinces between January 2005 to July 2007. Two hundred samples from
      potato and tomato were collected and analyzed by enzyme-linked immunosorbent
      assay (ELISA) for potyviruses. Almost one fourth of the samples were found to be
      infected by PVY. Analysis of these PVY-positive samples using three monoclonal
      antibodies (MAbs) facilitating the simultaneous detection of three main strains
      namely the ordinary (PVY(O)), strain (PVY(N)) and C (PVY(C)) strains. However,
      the fourth strain (PVY(NTN)) and some others recombinant isolates were also
      identified by molecular methods. Host range and symptoms analysis using sap
      inoculation of four different strains of PVY onto a range of plants revealed that
      the four strains showed biological properties that seemed to be consistent with
      their molecular grouping. Fourteen isolates of PVY were chosen based on the host
      and geographical location, primer specificity and serology for further biological
      and molecular characterisation. The coat protein (CP) and P1 genes and 3'-non
      translated region (3'NTR) from 14 representative isolates were sequenced and
      analysed with the sequences available in GenBank. Composite analysis of the P1,
      CP and 3'-UTR sequences with all full genome sequences of PVY revealed that there
      are three potential strains of PVY in Iran, PVY(O), PVY(N)-W and PVY(NTN).
      Isolate KER.SA(N) was the most divergent of all the 14 isolates reacted with
      PVY(N) specific MAbs but grouped with PVY(O) strains in maximum likelihood
      phylogentic analysis. The PVY(NTN) isolates from Iran more closely related to the
      European than North American PVY(NTN) isolates.

PMID- 21082230
TI  - Influenza A viruses: why focusing on M2e-based universal vaccines.
AB  - The threat of highly virulent avian influenza, such as H5N1 and swine-origin H1N1
      influenza viruses, bring out an urgent need to develop a universal influenza
      vaccine, which may provide cross-protection against different strain of influenza
      A viruses. The extra-domain of influenza M2 protein (M2e), which is almost
      completely conserved among all subtypes of influenza A viruses, is considered as
      a promising candidate target for the development of a broad-spectrum recombinant
      influenza A vaccine. The results of several preclinical studies with M2e protein,
      with or without carriers, have already proved the successful protection of M2e
      based vaccinated animal model against lethal challenge of heterologous and
      homologous influenza A viruses. Recently, the results of Phase I/II clinical
      trail studies with M2e-based vaccines have raised hopes for considering these
      vaccines against seasonal and pandemic influenza A strains. Hence, it is expected
      that more and more effective and safe universal influenza vaccines based on M2e
      will be developed for prevention of seasonal and pandemic influenza in the near
      future.

PMID- 21082232
TI  - Influence of gene variants related to calcium homeostasis on biochemical
      parameters of women with polycystic ovary syndrome.
AB  - PURPOSE: The purpose of this study was to evaluate the associations between
      polymorphisms in vitamin D receptor (VDR), parathyroid hormone (PTH), calcium
      sensing receptor (CASR), insulin receptor (INSR), and adiponectin (ADIPOQ) genes
      and biochemical characteristics of women with polycystic ovary syndrome (PCOS).
      METHODS: Serum levels of LH, FSH, estradiol, testosterone, prolactin, SHBG,
      glucose, IGF-1, IGFBP-1, calcium, phosphorus, PTH, 25(OH)D, and 1,25(OH)(2) D
      were measured in 56 women with PCOS. Furthermore, genotyping five, one, one, two,
      and two polymorphisms of the VDR, PTH, CASR, INSR, and ADIPOQ genes,
      respectively, were performed. RESULTS: The VDR TaqI "CC" genotype was associated
      with elevated serum levels of LH (p = 0.011). There were significant associations
      between decreased levels of SHBG and both VDR BsmI "GG" (p = 0.009) and ADIPOQ
      BsmI "CC" (p = 0.016) genotypes. Furthermore, patients with CaSR Hin1I "TG"
      genotype showed higher HoMA-IR (p = 0.008). All these associations remained
      significant after Bonferroni correction. In addition, phosphorus correlated
      negatively with estradiol (r =  -0.298, P = 0.026) and positively with glucose (r
      = 0.287, P = 0.032). CONCLUSIONS: These data indicated for the first time that it
      is possible that the VDR and CASR gene variants through their effects on LH and
      SHBG levels, and insulin resistance are involved in pathogenesis of PCOS.

PMID- 21082233
TI  - Long Y chromosome is not a fetal loss risk.
AB  - PURPOSE: To assess the long Y chromosome genetic effect on human pregnancy
      outcomes. METHODS: We studied all records of pregnancies by human sperm donors
      after artificial insemination or in vitro fertilization at the Reproductive and
      Genetic Hospital of Citic-Xiangya. Fetal losses were compared from two groups of
      sperm donors: the observation group (with long Y chromosome) and the control
      group (without long Y chromosome). RESULTS: 2885 pregnancies were achieved with
      donor sperm by artificial insemination and 1746 by in vitro fertilization. The
      rates of fetal loss, congenital malformation and donor fecundity in the
      observation group after both assisted reproductive technique were the same as for
      the control group. CONCLUSIONS: A long Y chromosome may therefore be considered
      as a normal variant.

PMID- 21082234
TI  - Evaluation of maturation competence of metaphase II oocytes in mice based on the
      distance between pericentriolar materials of meiotic spindle: distance of PCM
      during oocyte maturation.
AB  - PURPOSE: To ascertain whether metaphase II (MII) spindle shape influences oocyte
      competence, we examined the meiotic spindle organization in in vivo ovulated
      (IVO) oocytes and in spontaneously matured or follicle stimulating hormone (FSH)
      induced oocytes. METHODS: FSH-induced oocytes matured in Waymouth's MB752/1 or
      human tubal fluid (HTF) media and oocytes matured spontaneously in the basal
      medium were obtained, and spindles were detected by immunofluorescence. To
      evaluate the fertilization-associated differences in spindle morphology, we
      performed in vitro fertilization and analysed integrin mRNA expression. RESULTS:
      The distance between the pericentriolar materials (PCMs) in oocytes matured under
      all conditions was initially more, but it reduced gradually and increased again
      thereafter. Therefore, oocytes exhibiting a reduction in the distance between
      PCMs had the highest development rate to blastocyst in each condition.
      CONCLUSION: These results indicate that the 'maturation competence' of MII
      oocytes can be evaluated on the basis of the distance between PCMs.

PMID- 21082235
TI  - Identification of CD133(-)/telomerase(low) progenitor cells in glioblastoma
      derived cancer stem cell lines.
AB  - Glioblastoma multiforme (GBM) is paradigmatic for the investigation of cancer
      stem cells (CSC) in solid tumors. The CSC hypothesis implies that tumors are
      maintained by a rare subpopulation of CSC that gives rise to rapidly
      proliferating progenitor cells. Although the presence of progenitor cells is
      crucial for the CSC hypothesis, progenitor cells derived from GBM CSC are yet
      uncharacterized. We analyzed human CD133(+) CSC lines that were directly derived
      from CD133(+) primary astrocytic GBM. In these CSC lines,
      CD133(+)/telomerase(high) CSC give rise to non-tumorigenic, CD133(
      )/telomerase(low) progenitor cells. The proliferation of the progenitor cell
      population results in significant telomere shortening as compared to the CD133(+)
      compartment comprising CSC. The average difference in telomere length as
      determined by a modified multi-color flow fluorescent in situ hybridization was
      320 bp corresponding to 4-8 cell divisions. Taken together, we demonstrate that
      CD133(+) primary astrocytic GBM comprise proliferating, CD133(-)/telomerase(low)
      progenitor cell population characterized by low telomerase activity and shortened
      telomeres as compared to CSC.

PMID- 21082236
TI  - Neutralization of BDNF attenuates the in vitro protective effects of olfactory
      ensheathing cell-conditioned medium on scratch-insulted retinal ganglion cells.
AB  - Transplantation of olfactory ensheathing cells (OECs) becomes one of the
      promising strategies in restoring lost functions of injured central nervous
      system. Elevated level of expressed brain-derived neurotrophic factor (BDNF) was
      revealed in the previous studies to be related to the protective effects of OECs
      on injured cortical and brain stem neurons as well as retinal ganglion cells
      (RGCs), but no evidence has been obtained to demonstrate whether transplanted
      OECs protect injured central neurons directly by their secreted BDNF. In the
      present study, the effects of BDNF neutralization on the neuroprotection of adult
      OEC-conditioned medium (OEC-CM) on scratch-insulted RGCs were examined. The
      results showed that OEC-CM protected cultured RGCs from scratch insult, and
      neutralization of BDNF by BDNF neutralizing antibody attenuated such
      neuroprotection of the medium. It is thus concluded that neurotrophic factors
      including BDNF secreted by OECs can protect injured OECs in vitro and BDNF plays
      a major role in such a protection of OECs.

PMID- 21082237
TI  - Immunocytochemical localization of TASK-3 (K(2P)9.1) channels in monoaminergic
      and cholinergic neurons.
AB  - Monoaminergic and cholinergic systems are important regulators of cortical and
      subcortical systems, and a variety of vegetative functions are controlled by the
      respective neurotransmitters. Neuronal excitability and transmitter release of
      these neurons are strongly regulated by their potassium conductances carried by
      Kir and K(2P) channels. Here we describe the generation and characterization of a
      polyclonal monospecific antibody against rat TASK-3, a major brain K(2P) channel.
      After removal of cross-reactivities and affinity purification the antibody was
      characterized by ELISA, immunocytochemistry of TASK-3 transfected cells, and
      Western blots indicating that the antibody only detects TASK-3 protein, but not
      its paralogs TASK-1 and TASK-5. Western blot analysis of brain membrane fractions
      showed a single band around 45 kD, close to the predicted molecular weight of the
      TASK-3 protein. In addition, specific immunolabeling using the anti-TASK-3
      antibody in Western blot analysis and immunocytochemistry was blocked in a
      concentration dependent manner by its cognate antigen only. Immunocytochemical
      analysis of rat brain revealed strong expression of TASK-3 channels in
      serotoninergic neurons of the dorsal and median raphe, noradrenergic neurons of
      the locus coeruleus, histaminergic neurons of the tuberomammillary nucleus and in
      the cholinergic neurons of the basal nucleus of Meynert. Immunofluorescence
      double-labeling experiments with appropriate marker enzymes confirmed the
      expression of TASK-3 in cholinergic, serotoninergic, and noradrenergic neurons.
      In the dopaminergic system strong TASK-3 expression was found in the ventral
      tegmental area, whereas TASK-3 immunoreactivity in the substantia nigra compacta
      was only weak. All immunocytochemical results were supported by in situ
      hybridization using TASK-3 specific riboprobes.

PMID- 21082238
TI  - Evidence for ectopic aerobic ATP production on C6 glioma cell plasma membrane.
AB  - Extracellular ATP plays a pivotal role as a signaling molecule in physiological
      and pathological conditions in the CNS. In several glioma cell lines, ATP is a
      positive factor for one or more characteristics important for the abnormal growth
      and survival of these cells. This work presents immunofluorescence and
      biochemical analyses suggesting that an aerobic metabolism, besides mitochondria,
      is located also on the plasma membrane of C6 glioma cells. An ATP synthesis
      coupled to oxygen consumption was measured in plasma membrane isolated from C6
      cells, sensitive to common inhibitors of respiratory chain complexes, suggesting
      the involvement of a putative surface ATP synthase complex. Immunofluorescence
      imaging showed that Cytochrome c oxydase colocalized with WGA, a typical plasma
      membrane protein, on the plasma membrane of glioma cells. Cytochrome c oxydase
      staining pattern appeared punctuate, suggesting the intriguing possibility that
      the redox chains may be expressed in discrete sites on C6 glioma cell membrane.
      Data suggest that the whole respiratory chain is localized on C6 glioma cell
      surface. Moreover, when resveratrol, an ATP synthase inhibitor, was added to
      culture medium, a cytostatic effect was observed, suggesting a correlation among
      the ectopic ATP synthesis and the tumor growth. So, a potential direction for the
      design of new targets for future therapies may arise.

PMID- 21082239
TI  - Economic evaluation of the 21-gene signature (Oncotype DX) in lymph node
      negative/positive, hormone receptor-positive early-stage breast cancer based on
      Japanese validation study (JBCRG-TR03).
AB  - The 21-gene signature is validated as a good predictor of recurrence for lymph
      node-negative/positive, hormone receptor-positive, early-stage breast cancer in
      Japanese patient population. This study evaluates the cost-effectiveness of two
      scenarios designed to include the assay into Japan's social health insurance
      benefit package: one for LN-, ER+, ESBC and another for LN-/+, ER+, ESBC. An
      economic decision tree and Markov model under Japan's health system from the
      societal perspective is constructed with new evidence from the Japanese
      validation study. Incremental cost-effectiveness ratios are estimated as Y384,828
      (US$3,848) per QALY for the indication for LN- scenario and Y568,533 (US$5,685)
      per QALY for the indication for LN-/+ scenario. Both are not more than the
      suggested social willingness-to-pay for one QALY gain from an innovative medical
      intervention in Japan, Y5,000,000/QALY (US$50,000/QALY). Sensitivity analyses
      show that this result is plausibly robust, since ICERs do not exceed the
      threshold by various changes of assumptions made and values employed. In
      conclusion, the inclusion of the assay in Japan's social health insurance benefit
      package for not only LN- diseases but also LN+ diseases is cost-effective. Such a
      decision can be justifiable as an efficient use of finite resources for health
      care.

PMID- 21082240
TI  - Influence of pH upon the activity of glycosidases and proteinases of intestinal
      mucosa, chyme and microbiota in fish.
AB  - It is shown that amylolytic and proteolytic activity of the intestinal mucosa,
      the chyme and the intestinal flora in the fishes, zander Zander lucioperca (L.),
      perch Perca fluviatilis L., bream Abramis brama (L.) and roach Rutilus rutilus
      (L.), belonging according to their feeding habits to different ecological groups
      at the same pH values as well as in the pH range from 5.0 to 10.0 considerably
      varies. The glycosidase pH optimum of the mucosa and intestinal microbiota is
      7.0, whereas that of the chyme varies from 6.0 (in roach) to 8.0 (in bream). pH
      optimum of the mucosa proteinases in all fish species is 10.0, whereas that of
      the chyme and the bacterial flora can be observed in all the range of pH values.

PMID- 21082241
TI  - Rapid changes in heat-shock cognate 70 levels, heat-shock cognate phosphorylation
      state, heat-shock transcription factor, and metal transcription factor activity
      levels in response to heavy metal exposure during sea urchin embryonic
      development.
AB  - The aim of the present study was to analyze and compare the effects of several
      metals on the embryos of the sea urchin Paracentrotus lividus, a key species
      within the Mediterranean Sea ecosystem. Embryos were continuously exposed from
      fertilization to the following metals: 0.6 mg/l copper, 3 mg/l lead, and 6 mg/l
      nickel. The embryos were then monitored for metal responses at the gastrula
      stage, which occurred 24 h after exposure. A biochemical multi-experimental
      approach was taken and involved the investigation of the levels of HSC70
      expression and the involvement of heat shock factor (HSF) and/or metal
      transcription factor (MTF) in the response. Immunoblotting assays and
      electrophoretic mobility shift assays (EMSA) were used to detect stress protein
      levels and to study the interaction between DNA and specific transcription
      factors, respectively. In the 1 h during exposure to heavy metals, changes in
      HSC70 levels and HSC70 a phosphorylation state were observed. Rapid changes in
      HSF and MTF DNA-binding activity also occurred during the early stages of heavy
      metal exposure. In contrast, few developmental abnormalities were observed at the
      gastrula stage but more abnormalities were observed 48 h after metal exposure.
      These data demonstrate that changes in HSC70 levels and phosphorylation state as
      well as in HSF and MTF binding activities may be used to rapidly detect responses
      to heavy metal exposure. Detection of biochemical and molecular changes in
      response to metal exposure before manifestation of morpho-pathological effects
      are important for the prediction of morbidity, and these markers will be useful
      for determining the response to exposure as part of a toxicological exposure
      response experiment and for determining responses for an impact assessment.

PMID- 21082242
TI  - Mercury in breeding and wintering Nelson's Sparrows (Ammodramus nelsoni).
AB  - The objective of this study was to increase our understanding of Hg exposure in
      birds with obligate ties to coastal salt marsh and inland wetland systems. Many
      species filling such niches are of conservation concern because of reduced size
      and quality of vital habitats. We used Nelson's Sparrow (Ammodramus nelsoni) as
      an indicator of regional mercury (Hg) availability in its breeding and wintering
      salt marsh and wetland habitats. Blood, breast feathers and the first primary
      feather were sampled from Nelson's Sparrows wintering in North Carolina coastal
      salt marshes and breeding in wetland systems in North Dakota (A. n. nelsoni) and
      Ontario, Canada (A. n. alterus). Wintering Nelson's Sparrow breast feathers
      contained 3.0 times as much Hg as birds breeding in North Dakota and 2.4 times as
      much Hg as those breeding in Ontario. Breeding Nelson's Sparrows in North Dakota
      exhibited blood Hg levels 4.9 times as high as those from birds breeding along
      James Bay and 7.6 times as high as those wintering in North Carolina. These
      results provide significant insight on the timing of molt in this species as well
      as how Hg exposure varies regionally and seasonally for these birds. Further, our
      results provide a better understanding of how and where Hg exposure may be a
      threat to Nelson's Sparrows and other birds with obligate ties to aquatic
      systems.

PMID- 21082243
TI  - Toxicity of the amphoteric surfactant, cocamidopropyl betaine, to the marine
      macroalga, Ulva lactuca.
AB  - The degradation of the synthetic, amphoteric surfactant, cocamidopropyl betaine
      (CAPB) and its toxicity to the marine macroalga, Ulva lactuca, has been evaluated
      using several different physiological test end-points over different periods of
      exposure up to 120 h. Droplet surface angle measurements revealed that, following
      a period of acclimation of about 24 h, CAPB began to degrade and that primary
      degradation was complete within 120 h. Effective quantum yield (?F/F(m)') and
      relative growth rates (RGRs) were the most sensitive measures of phytotoxicity,
      with CAPB concentrations at and above 10 mg l(-1) eliciting irreversible, time
      dependent and/or dose-dependent responses. Cell membrane damage, estimated from
      measurements of ion leakage, was detected only at a concentration of 40 mg l(-1)
      after 48 h of exposure to CAPB but by 120 h damage was evident at all measured
      concentrations above 10 mg l(-1). These observations suggest that both CAPB and
      its metabolites are intrinsically toxic to U. lactuca. The findings of this study
      are discussed in terms of the environmental consequences of applying CAPB to
      control harmful algal blooms.

PMID- 21082244
TI  - Safety assessment of sFat-1 transgenic pigs by detecting their co-habitant
      microbe in intestinal tract.
AB  - Transgenic pigs containing sFat-1 (synthesized fatty acid desaturase-1) gene were
      produced by DNA microinjection. The meat of these pigs contain omega-3
      unsaturated fatty acid which is beneficial to the health of human being. The aim
      of this study is to assess the effects of expression of sFat-1 in pig on the
      health of animal themselves and on the safety of environment from the angle of
      the changes in microbe population of pig intestinal tract. Four F1 male semi
      sibling of sFat-1 transgenic pigs and four F1 female semi-sibling of sFat-1
      transgenic pigs were used as experimental animals, together with their none
      transgenic siblings as control animals. For inspection of any change in
      populations of microbial flora in various parts of intestinal tract and feces of
      sFat-1 transgenic pigs total aerobe, total anaerobe, main beneficial bacteria and
      main harmful bacteria were cultured and analyzed. At the same time foreign gene
      drift was assessed by PCR amplifying foreign fragment in samples of total aerobe
      and total anaerobe. Results indicated that in comparison with control pig microbe
      population of various species in different parts of intestinal tract and feces of
      sFat-1 transgenic pig remained unchanged and foreign gene sequence could not be
      detected in DNA of total aerobe and total anaerobe. In conclusion, the data of
      this study suggest that microbe population in intestinal tract and feces of
      transgenic pig was not influenced by the expression of transferred foreign gene
      sFat-1 and also foreign gene drifting from animal genome to microbial genome must
      be a rare incident.

PMID- 21082245
TI  - Brucellosis seroprevalence in livestock in Uganda from 1998 to 2008: a
      retrospective study.
AB  - A total of 17,359 samples were analysed serologically, of which 1,061, 15,758 and
      585 samples were from Makerere, Entebbe and Tororo laboratories, respectively,
      were used to determine the seroprevalence of brucellosis. The overall
      seroprevalence of brucellosis was 10% while from individual laboratories was 38%,
      32% and 7% for Makerere, Entebbe and Tororo laboratories, respectively. Majority
      of these positive brucellosis test results were in the cattle corridor with P
      value = 0.399. There were significant differences in brucellosis seroprevalence
      among species (P value = 0.014). The trends of brucellosis seroprevalence among
      the different species were decreasing with time but were highest in bovine
      species (P value = 0.043). Brucellosis seroprevalence had a bimodal monthly
      pattern corresponding with rainfall. The study showed that brucellosis was
      prevalent, though the trend of the disease has declined over years. It was
      recommended that regular disease surveillance, control programmes and further
      studies be carried out in the country.

PMID- 21082246
TI  - Village livestock population and sampling strategies in communal areas in the
      Eastern Cape Province, South Africa.
AB  - There is an urgent need for a livestock census in communal areas of the Eastern
      Cape Province, South Africa. This study focuses on the description of the cattle,
      sheep, and goat populations with emphasis on the livestock distributions and
      population characteristics in a pilot study in two wards in communal farm land.
      In one of the wards, sample homogeneity was found in the cattle and goat
      populations. In contrast, in the second ward sheep and goat populations were
      found heterogeneous, and only cattle showed homogeneity. As a consequence, the
      use of a simple random sampling strategy for the livestock population can be
      recommended in one ward whereas a more complex stratified random sampling
      strategy is recommended for the other. The organization and logistics costs must
      be taken into consideration when organizing a livestock census. Therefore, the
      observations of this study prepare the decision on sampling schemes for future
      census activities. The possibility of using a complete enumeration census should
      not be discarded especially in areas with heterogeneous livestock populations
      where the organization of a complex sampling strategy can prove to be time
      consuming and complicated to be executed in the field.

PMID- 21082247
TI  - Seroprevalence of Brucella infection in yaks (Bos grunniens) on the Qinghai-Tibet
      plateau of China.
AB  - The seroprevalence of Brucella infection in yaks was surveyed on the Qinghai
      Tibet plateau of China in 2010. A total of 621 serum samples was collected from
      six counties and were tested by serum agglutination test. The results showed that
      56 (9%) of the samples were positive for Brucella. The results of the present
      investigation indicate that brucellosis is common in yaks on the Qinghai-Tibet
      plateau of China.

PMID- 21082248
TI  - Growth performance, carcass characteristics and meat sensory evaluation of West
      African dwarf sheep fed varying levels of maize and cassava hay.
AB  - A study was conducted to determine the growth performance and meat yield and
      quality of West African dwarf sheep. Twenty rams weighing an average of 15.3 +/-
      0.79 kg live weight and with an average age of 18 months were allotted at random
      to five dietary treatments of 0%, 25%, 50%, 75% and 100% maize hay (MH) for a
      period of 105 days. Dry matter (DM) intake and growth rate of the rams were
      improved as the level of cassava hay (CH) increased in the diets. Live weight
      gain varied significantly (P < 0.05) across the treatments, ranging from 38.8 to
      47.9 g/day. The carcass weight of the rams fed 100% MH was significantly (P <
      0.05) lower compared with the other treatments. Dressing percentage ranged from
      56.5% to 61.0% with no significant (P > 0.05) difference observed across the
      treatments, while the distribution of the slaughtered parts was similar (P >
      0.05) regardless of the dietary treatment. Proximate composition of the meat from
      the loin indicated that the DM, crude protein, fat and ash contents were not
      influenced (P > 0.05) by the dietary treatments. Panellists rated the meat to be
      similar (P > 0.05) in flavour, juiciness, tenderness and overall acceptability
      while colour and texture varied significantly (P < 0.05) across the treatments.
      In conclusion, this study indicated that better growth performance and meat
      production in West African dwarf sheep can be improved in form of body weight and
      carcass production when fed 25%MH and 75% CH diet.

PMID- 21082249
TI  - Normal bacterial flora from vaginas of Criollo Limonero cows.
AB  - In order to describe the normal bacterial flora in vaginas of Criollo Limonero
      cows, 51 healthy multiparous cows, at least 90-day postpartum, were selected.
      Duplicated swabs (N = 102) were taken from the vaginal fornix of cows to perform
      aerobic and anaerobic cultures as well as conventional biochemical tests. Out of
      102 swabs, bacterial growth was obtained in 55 (53.9%) while the remaining 47
      (46.1%) did not exhibited any bacterial growth. Of the 55 bacterial growths, 23
      (41.8%) were aerobic whereas 32 (58.1%) were anaerobic. Likewise, 29 (52.72%) of
      bacterial growths were pure and 26 (47.27%) were mixed. Under both aerobic and
      anaerobic conditions, Gram positive bacteria were predominant (81.82% and 73.08%,
      respectively) over Gram negative bacteria (18.18% and 26.92%, respectively).
      Isolated bacteria were Arcanobacterium pyogenes (22.92%), Staphylococcus aureus
      (15.63%), Staphylococcus coagulase negative (17.71%), Erysipelothrix
      rhusiopathiae (6.25%), Bacteroides spp. (13.54%), and Peptostreptococcus spp.
      (7.29%). In conclusion, normal vaginal bacterial flora of Criollo Limonero cows
      was predominantly Gram positive and included A. pyogenes, S. aureus, coagulase
      negative Staphylococcus, E. rhusiopathiae, Bacteroides spp., and
      Peptostreptococcus spp. In Criollo Limonero cattle, adaptive aspects such as
      development of humoral and physical mechanisms for defense, and bacterial
      adaptation to host deserve research attention.

PMID- 21082250
TI  - ESPVR, ejection fraction and heart failure.
AB  - The problem of heart failure with preserved ejection fraction (HFpEF) has
      recently received much attention. In this study we discuss some relations that
      connect ejection fraction EF to the parameters describing the end-systolic
      pressure-volume relation (ESPVR). It is shown that the study of the relation
      between EF and ESPVR can give some understanding of the problem of HFpEF. An
      important feature of the present approach is the introduction of the active force
      of the myocardium (also called isovolumic pressure) in the formalism describing
      the ESPVR.

PMID- 21082251
TI  - Subthreshold parameters of cardiac tissue in a bi-layer computer model of heart
      failure.
AB  - Current density threshold and liminal area are subthreshold parameters of the
      cardiac tissue that indicate its susceptibility to external and internal
      stimulations. Extensive experimental and theoretical research has been conducted
      to quantify these two parameters in normal conditions for both animal and human
      models. Here we employed a 2D numerical model of human cardiac tissue to assess
      these subthreshold parameters under the pathological conditions of heart failure
      and fibrosis. Stimuli were applied over an area ranging from 0.04 to 1 mm2 using
      various pulse durations. The current density threshold decreased with increasing
      stimulation area or pulse duration. No significant changes were found in both
      parameters between control conditions and heart failure in the atrial tissue,
      while in the ventricular tissue, heart failure resulted in significantly reduced
      excitability with higher stimulation current magnitudes needed for excitation and
      larger liminal areas. This results from the specific ionic remodeling in
      ventricular heart failure that affects both subthreshold active currents such as
      I(K1) and connexin 43 conductance. In fibrosis, increased fibroblast to myocyte
      coupling coefficient had a non-linear influence on current density thresholds,
      with an initial increase of current magnitude followed by a relaxation phase down
      to the current magnitude threshold for the control condition with no fibrosis.
      The results show that subthreshold excitation properties of the myocardium are
      influenced in a complex, non-linear manner by cardiac pathologies. Such
      observations may contribute to our understanding of impulse capturing properties,
      relevant, for example, for the generation of ectopic foci-originated arrhythmias
      and for the efficient design of cardiac stimulating electrodes.

PMID- 21082252
TI  - Intention to change dietary habits, and weight loss among Norwegian-Pakistani
      women participating in a culturally adapted intervention.
AB  - The aim was to explore the relationships between degree of participation in a
      culturally adapted lifestyle intervention and stages of change for healthy eating
      and weight loss among Pakistani immigrant women in Norway. The intervention
      lasted 7 months and included 198 women, randomized into control and intervention
      groups. The odds of losing weight from baseline to follow-up, and being in action
      stages of change (compared to pre-action stages) with regard to intake of amount
      and type of fat, sugar and white flour at follow-up, increased significantly with
      number of group sessions attended. Those in action stage of reducing intake of
      fat and increasing intake of vegetables, as well as of reducing weight, were
      significantly more likely than others to have experienced weight loss at follow
      up. Participation in the culturally adapted intervention was related to increase
      in intentions to change dietary behaviours and to weight loss.

PMID- 21082253
TI  - A review on the oral health impacts of acculturation.
AB  - The impact of acculturation on systemic health has been extensively investigated
      and is regarded as an important explanatory factor for health disparity. However,
      information is limited and fragmented on the oral health implications of
      acculturation. This study aimed to review the current evidence on the oral health
      impact of acculturation. Papers were retrieved from five electronic databases.
      Twenty-seven studies were included in this review. Their scientific quality was
      rated and key findings were summarized. Seventeen studies investigated the
      impacts of acculturation on the utilization of dental services; among them, 16
      reported positive associations between at least one acculturation indicator and
      use of dental services. All 15 studies relating acculturation to oral diseases
      (dental caries and periodontal disease) suggested better oral health among
      acculturated individuals. Evidence is lacking to support that better oral health
      of acculturated immigrants is attributable to their improved dental attendance.
      Further researches involving other oral health behaviors and diseases and
      incorporating refined acculturation scales are needed. Prospective studies will
      facilitate the understanding on the trajectory of immigrants' oral health along
      the acculturation continuum.

PMID- 21082254
TI  - Role of echocardiography in the assessment and management of adult congenital
      heart disease in pregnancy.
AB  - Congenital heart disease represent a large proportion of heart disease in
      pregnancy. With the exception of patients with Eisenmenger's syndrome, pulmonary
      vascular obstructive disease, and Marfan's syndrome with aortopathy, maternal
      death during pregnancy is rare in women with CHD but morbidity occurs such as
      heart failure, arrhythmias, and stroke. Echocardiography represents a milestone
      in diagnosis, understanding of pathophysiology, assessment of disease severity
      and patient monitoring in pregnant women with unoperated and post-operative
      congenital heart disease.

PMID- 21082256
TI  - Cell wall glycoproteins participate in the adhesion of Sporothrix schenckii to
      epithelial cells.
AB  - Sporothrix schenckii is the etiologic agent of sporotrichosis. This fungal
      infection is an emerging disease potentially fatal in immunocompromised patients.
      The adhesion to host cells is a crucial early event related with the
      dissemination of pathogens. In order to clarify the mechanisms of adhesion of S.
      schenckii yeast cell to epithelial cells, we studied the biochemical basis of
      this process. The electrophoretic analysis of cell wall protein from S. schenckii
      coupled at ConA and stained with HRP, revealed nine different proteins with MW >=
      180, 115, 90, 80, 58, 40, 36, 22 and 18 kDa. Using ligand-like assay with
      biotinylated S. schenckii surface proteins, five proteins with MW >= 190, 180,
      115, 90 and 80 kDa which have affinity to epithelial cells were identified. The
      adhesion of yeast to epithelial monolayer was significantly inhibited when S.
      schenckii was pretreated with concanavalinA (ConA) and wheat germ agglutinin
      (WGA) lectins, alkali, periodate, trypsin, endoglycosidase H (EndoH), salt
      solutions and detergents. The ability of adhesion of S. schenckii yeast was
      recovered by blocking the lectin with sugar complementary. These data suggest
      that surface glycoprotein with mannose and glucose residue could be participate
      in the process of fungal adhesion to epithelial cells.

PMID- 21082255
TI  - Serial angiographic and intravascular ultrasound evaluation to interrogate the
      presence of late "catch-up" phenomenon after Cypher(r) sirolimus-eluting stent
      implantation.
AB  - Despite the expressive reduction in the intimal hyperplasia (IH) formation after
      DES implantation at the mid-term, late restenosis has been recently noticed. Our
      objective was to determine, by means of serial angiography (QCA) and
      intravascular ultrasound (IVUS) at two different time points, whether the
      occurrence of the "late catch-up" phenomenon occurs after sirolimus-eluting stent
      (SES) implantation. Thirty-eight non-complex patients treated with a single 18-mm
      SES who had systematic serial QCA and IVUS analyses at mean 8 and 20 months were
      enrolled. Primary endpoint is to evaluate the temporal course of IH formation
      after SES implantation, by comparing QCA in-stent late loss and IVUS percent IH
      obstruction between the invasive follow-ups. Mean cohort age was 59.3 years and
      31.6% were diabetics. Baseline reference vessel diameter was 2.8 +/- 0.4 mm and
      lesion length was 11.5 +/- 3.5 mm. Left anterior descending artery was the most
      frequent target vessel (55.3%). Between 8 and 20 months, a non-significant
      increase in in-stent late loss from 0.10 +/- 0.18 to 0.15 +/- 0.30 mm (P = 0.38)
      was observed. By IVUS, a slight increase in the percent IH obstruction (1.03 +/-
      2.13 to 1.76 +/- 1.87%, P = 0.12) was detected between the two evaluations.
      Interestingly, all the neoformed tissue accrued from 8 to 20 months accumulated
      in the distal portion of the stent. In the non-complex scenario, SES implantation
      was associated with a minimal, non-significant increase in the IH volume between
      8 and 20 months.

PMID- 21082257
TI  - Novel SNPs in HSP70A1A gene and the association of polymorphisms with thermo
      tolerance traits and tissue specific expression in Chinese Holstein cattle.
AB  - Heat stress induces heat shock proteins (HSPs) expression and HSP70 family is one
      of them that have been reported to involve in cellular protection against heat
      stress. But whether there is any association of genetic variation in the HSP70A1A
      gene with thermo tolerance is unknown. PCR-SSCP and DNA sequencing were used to
      detect possible SNPs in HSP70A1A gene in 890 Chinese Holstein cattle. Three
      fragments were amplified and five novel mutations were found in HSP70A1A gene in
      Chinese Holstein cattle. G/A mutation was found at nucleotide 1524 in coding
      region that resulting two genotypes of AA and AB. T/C mutation was found at
      nucleotide 3494 in 3'-UTR resulting three genotypes of CC, CD and DD. The other
      three point mutations, G/C at nucleotide 6400, C/T at nucleotide 6600 and G/A at
      nucleotide 6601 were also found in 3'-UTR resulting six genotypes of EE, EF, FF,
      EG, FG and GG. Linkage disequilibrium (LD) analysis showed that the nucleotide
      6400, 6600 and 6601 were in strong LD (D>0.75). Association analysis indicated
      that AB, DD and FF genotype were the thermo tolerance genotype. SBYE Green I was
      used to quantify HSP70A1A mRNA expression in different tissues through
      quantitative real-time PCR assay. The results of the real-time PCR showed that
      the expression of HSP70A1A mRNA in the heart was significantly higher than that
      in the other tissues (P<0.05). We presume that these mutations could be used in
      marker assisted selection for anti-heat stress cows in our breeding program.

PMID- 21082258
TI  - Molecular characterization, expression patterns and polymorphism analysis of
      porcine Six1 gene.
AB  - Six1 belongs to the Six gene family that includes six members in mammals (from
      Six1 to Six6). It has been demonstrated that Six1 homeodomain transcription
      factor is implicated in myogenesis. However, the molecular characteristics of
      Six1 in pigs have not been reported. In this study, we isolated and characterized
      the porcine Six1 gene full-length cDNA, genomic DNA and proximal promoter
      sequence. Semi-quantitative RT-PCR results confirmed that porcine Six1 was highly
      expressed in skeletal muscle. Real-time quantitative PCR results showed that
      porcine Six1 was highly expressed in embryonic stage and no significant
      expression differences is observed between Meishan and Yorkshire pigs.
      Furthermore, Six1 expression was significantly different among different
      developmental stages in Yorkshire pigs and the expression trend was up-regulated
      from 3 days to 180 days, reaching its highest expression level at 180 days. In
      addition, the data of Six1 expression in different muscles demonstrated that Six1
      was a fast-twitch muscle high expression gene. PCR-HindII-RFLP was established to
      detect a C/T mutation and an A/G mutation which were present in promoter and
      intron, respectively. Meanwhile, their associations with economic traits were
      assessed in Meishan * Yorkshire F2 reference family. The statistical results
      revealed that the two HindII polymorphisms of porcine Six1 had significant
      associations with several meat quality traits (P<0.05). Taken together, these
      studies suggest that porcine Six1 may play an important role in skeletal muscle
      growth and meat quality.

PMID- 21082259
TI  - Role of tissue plasminogen activator and plasminogen activator inhibitor
      polymorphism in myocardial infarction.
AB  - A case-control association study on 229 Myocardial Infarction (MI) patients and
      217 healthy controls was carried out to determine the role of tissue-plasminogen
      activator (t-PA) (Alu-repeat insertion (I)/deletion (D)) and plasminogen
      activator inhibitor (PAI-1) (4G/5G insertion/deletion) polymorphisms with MI in
      the Pakistani population. In MI patients the genotype distribution of the PAI-1
      gene was not found to be different when compared with the unaffected controls
      (P>0.05, chi2=1.03). The risk allele 4G was also not associated with MI (P>0.05,
      chi2=0.46, odds ratio (OR)=1.1 (95% confidence interval (CI)=0.84-1.43), P>0.05).
      Similarly, the genotype frequencies of t-PA I/I, I/D and D/D were not different
      from the unaffected controls (P>0.05, chi2=1.60), and the risk allele "I" was not
      found to be associated with MI (P>0.05, chi2=1.35, OR=0.86 (95% CI=0.66-1.11),
      P>0.05). However, when the data were distributed along the lines of gender a
      significant association of the 4G/4G PAI-1 genotype was observed with only the
      female MI patients (P<0.05, z-test=2.21). When the combined genotypes of both the
      polymorphisms were analyzed, a significant association of MI was observed with
      the homozygous DD/4G4G genotype (P<0.01, z-test=2.61), which was specifically
      because of the female samples (P=0.01, z-test=2.53). In addition smoking
      (P<0.001, chi2=13.52, OR=3.45 (95% CI=1.77-6.94)), diabetes (P<0.001, chi2=22.45,
      OR=8.89 (95% CI=2.96-29.95)), hypertension (OR=7.76 (95% CI=2.88-22.68), P<0.001)
      family history (P<0.001, chi2=13.72, OR=3.7 (95% CI=1.71-8.18)) and lower HDL
      levels (P<0.05) were found to be significantly associated with the disease. In
      conclusion the PAI-1 gene polymorphism was found to have a gender specific role
      in the female MI patients.

PMID- 21082261
TI  - Identification of adipose differentiation-related protein gene in Peking duck and
      its expression profile in various duck tissues.
AB  - Adipose differentiation-related protein (ADRP) is a protein which induced during
      the early onset of the adipose differentiation program and is expressed at high
      level in mature adipocytes. In the present study, 1311 bp of ADRP in Peking duck
      (Anas platyrhynchos) was cloned by reverse transcription (RT)-PCR. The cloned
      sequence of ADRP was highly conserved, although relevant changes with respect to
      human, mouse and chicken were identified. Real-time quantitative PCR was used to
      determine if the ADRP was expressed in different tissues of male and female
      Peking ducks. The expression of ADRP was widely distributed in all examined
      tissues. The expression level of it was highest in abdominal fat and lowest (only
      few) in lung of male and female Peking ducks.

PMID- 21082260
TI  - Genetic polymorphisms of glutathione S-transferase M1 and bladder cancer risk: a
      meta-analysis of 26 studies.
AB  - Studies investigating the association between glutathione S-transferase M1
      (GSTM1) polymorphism and bladder cancer risk report conflicting results. The
      objective of this study was to quantitatively summarize the evidence for such a
      relationship. We performed a systematic search of the National Library of Medline
      and Embase databases. This meta-analysis included 26 case-control studies, which
      included 5029 bladder cancer cases and 6680 controls. The combined results based
      on all studies showed that the GSTM1 null genotype was associated with an
      increased risk of bladder cancer (OR=1.46, 95% confidence interval [CI]=1.35,
      1.57). When stratifying for race, results were similar among Asians (OR=1.60, 95%
      CI=1.27, 2.01) and Caucasians (OR=1.44, 95% CI=1.33, 1.57) except Africans
      (OR=1.25, 95% CI=0.76, 2.06). When stratifying by the smoking, stage, grade, and
      histological type of bladder cancer, we found no statistical association. Our
      meta-analysis suggests that the GSTM1 null genotype is associated with a modest
      increase in the risk of bladder cancer.

PMID- 21082262
TI  - Candidate genes involved in tanshinone biosynthesis in hairy roots of Salvia
      miltiorrhiza revealed by cDNA microarray.
AB  - Salvia miltiorrhiza is a valuable Chinese herb (Danshen) that is widely used in
      traditional Chinese medicine. Diterpene quinones, known as tanshinones, are the
      main bioactive components of S. miltiorrhiza; however, there is only limited
      information regarding the molecular mechanisms underlying secondary metabolism in
      this plant. We used cDNA microarray analysis to identify changes in the gene
      expression profile at different stages of hairy root development in S.
      miltiorrhiza. A total of 203 genes were singled out from 4,354 cDNA clones on the
      microarray, and 114 unique differentially expressed cDNA clones were identified:
      six genes differentially expressed in 45-day hairy root compared with 30-day
      hairy root; 96 genes differentially expressed in 60-day hairy root compared with
      30-day hairy root; and 12 genes unstably expressed at different stages. Among the
      96 genes differentially expressed in 60-day hairy root compared with 30-day hairy
      root, a total of 57 genes were up-regulated, and 26 genes represent 29 metabolism
      related enzymes. Copalyl diphosphate synthase, which catalyzes the conversion of
      the universal diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate to copalyl
      diphosphate, was up-regulated 6.63 fold, and another six genes involved in
      tanshinone biosynthesis and eight candidate P450 genes were also differentially
      expressed. These data provide new insights for further identification of the
      enzymes involved in tanshinone biosynthesis.

PMID- 21082263
TI  - Single amino acid residue changes in subsite -1 of levansucrase from Zymomonas
      mobilis 10232 strongly influence the enzyme activities and products.
AB  - The -1 subsite of bacterial fructansucrases (FSs) (levansucrases and
      inulosucrases) plays an important role in the substrate recognition, binding and
      catalysis. Three residues (for example W47, W118 and R193, Zymomonas mobilis
      levansucrase numbering) at the -1 subsite are completely conserved among FSs.
      Site-directed mutational analysis showed that the substitutions of the three
      strictly conserved amino acid residues, W47N, W47H, W118N, W118H, R193K and
      R193H, significantly decreased enzyme activities and synthesis rates of levan,
      while the size of the synthesized oligosaccharides had been influenced. These
      experimental results, combined with 3D structure modeling, lead to our proposal
      that a single amino acid residue change in subsite -1 of levansucrase can
      influence change to the size and polarity of the sucrose binding pocket with a
      concomitant change to substrate binding and catalysis, and thus having an overall
      influence on the enzyme activities and products.

PMID- 21082264
TI  - Cloning, characterization, expression, and copper sensitivity of the
      metallothionein-1 gene in the Chinese mitten crab, Eriocheir sinensis.
AB  - A full-length metallothionein-1(MT-1) cDNA was cloned from the Chinese mitten
      crab, Eriocheir sinensis, based upon the hepatopancreas cDNA library. The full
      length cDNA contained a single 180 bp open reading frame that encoded a 59 amino
      acid protein. The deduced amino acid sequence was cysteine (Cys)-rich, with
      residues observed in patterns characteristic of other reported MTs: Cys-X-Cys,
      Cys-X-X-Cys, or Cys-X-X-X-Cys. Gene structure obtained via PCR yielded a 3816 bp
      gene, which was comprised of three exons and two introns arranged in a "3 + 2"
      pattern. The cloned 5'flanking region (1,735 bp) contained several predicted
      binding sites, which included MREs, AP-1, SP1, USF, GATA, HNF-1, and HSF. MT-1
      mRNA expression analysis revealed that while levels were highest in the
      hepatopancreas, expression was abundant in testis and thoracic ganglia, moderate
      in intestine (P<0.05), and weak in other tissues (P<0.05). MT-1 mRNA expression
      exhibited reproductive variation in the male, with levels approximately tenfold
      greater in August, during seasonal gonadal maturation, compared to other times of
      the year. Cu2+ exposure via tank water (0-1 mg/l for 7 days) resulted in a dose
      dependent bell curve response in MT-1 mRNA expression, with peak expression
      observed after exposure to 0.1 mg/l Cu2+. A time course experiment (0.1 mg/l Cu2+
      over 9 days) revealed MT-1 mRNA expression peaked sharply on day 5 before
      gradually decreasing with prolonged exposure. In the present report, we provide
      sequence analysis of the first MT-1 gene cloned in E. sinensis, and evidence that
      its physiological and toxicological regulation is evolutionary conserved.

PMID- 21082265
TI  - The enhancement of propyl gallate-induced HeLa cell death by MAPK inhibitors is
      accompanied by increasing ROS levels.
AB  - Propyl gallate (PG) as a synthetic antioxidant exerts a variety of effects on
      tissue and cell functions. Here, we investigated the effects of MAPK (MEK, JNK
      and p38) inhibitors on PG-treated HeLa cells in relation to cell death, ROS and
      GSH levels. PG induced cell growth inhibition and apoptosis in HeLa cells, which
      was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsim).
      ROS levels were increased or decreased in PG-treated HeLa cells depending on the
      incubation times. PG also increased GSH depleted cell numbers in HeLa cells. All
      the MAPK inhibitors slightly enhanced cell growth inhibition, death and MMP
      (DeltaPsim) loss, and increased ROS levels in PG-treated HeLa cells. However,
      MAPK inhibitors did not significantly affect GSH depletion in PG-treated cells.
      In conclusion, the enhanced effect of MAPK inhibitors on PG-induced HeLa cell
      death was accompanied by increasing ROS levels but the effect was not related to
      changes of GSH level.

PMID- 21082266
TI  - Anhedonia is associated with poor health status and more somatic and cognitive
      symptoms in patients with coronary artery disease.
AB  - PURPOSE: The effectiveness of cardiac rehabilitation (CR) in patients with
      coronary artery disease (CAD) is moderated by negative emotions and clinical
      factors, but no studies evaluated the role of positive emotions. This study
      examined whether anhedonia (i.e. the lack of positive affect) moderated the
      effectiveness of CR on health status and somatic and cognitive symptoms. METHODS:
      CAD patients (n = 368) filled out the Hospital Anxiety and Depression Scale
      (HADS) to assess anhedonia at the start of CR, and the Short-Form Health Survey
      (SF-36) and the Health Complaints Scale (HCS) at the start of CR and at 3 months
      to assess health status and somatic and cognitive symptoms, respectively.
      RESULTS: Adjusting for clinical and demographic factors, health status improved
      significantly during the follow-up (F(1,357) = 10.84, P = .001). Anhedonic
      patients reported poorer health status compared with non-anhedonic patients, with
      anhedonia exerting a stable effect over time (F(1,358) = 34.80, P < .001).
      Somatic and cognitive symptoms decreased over time (F(1,358) = 3.85, P = .05).
      Anhedonics experienced more benefits in terms of somatic and cognitive symptoms
      over time (F(1,358) = 13.00, P < .001). CONCLUSION: Anhedonic patients reported
      poorer health status and higher levels of somatic and cognitive symptoms prior to
      and after CR. Somatic and cognitive symptoms differed as a function of anhedonia
      over time, but health status did not. Anhedonia might provide a new avenue for
      secondary prevention in CAD.

PMID- 21082268
TI  - Practice based evidence of the beneficial impact of PET in patients with brain
      tumors.

PMID- 21082267
TI  - Recent advances in the genetics of SDH-related paraganglioma and
      pheochromocytoma.
AB  - The last 10 years have seen enormous progress in the field of paraganglioma and
      pheochromocytoma genetics. The identification of the first gene related to
      paraganglioma, SDHD, encoding a subunit of mitochondrial succinate dehydrogenase
      (SDH), was quickly followed by the identification of mutations in SDHC and SDHB.
      Very recently several new SDH-related genes have been discovered. The SDHAF2 gene
      encodes an SDH co-factor related to the function of the SDHA subunit, and is
      currently exclusively associated with head and neck paragangliomas. SDHA itself
      has now also been identified as a paraganglioma gene, with the recent
      identification of the first mutation in a patient with extra-adrenal
      paraganglioma. Another SDH-related co-factor, SDHAF1, is not currently known to
      be a tumor suppressor, but may shed some light on the mechanisms of
      tumorigenesis. An entirely novel gene associated with adrenal pheochromocytoma,
      TMEM127, suggests that other new paraganglioma susceptibility genes may await
      discovery. In addition to these recent discoveries, new techniques related to
      mutation analysis, including genetic analysis algorithms, SDHB
      immunohistochemistry, and deletion analysis by MLPA have improved the efficiency
      and accuracy of genetic analysis. However, many intriguing questions remain, such
      as the striking differences in the clinical phenotype of genes that encode
      proteins with an apparently very close functional relationship, and the lack of
      expression of SDHD and SDHAF2 mutations when inherited via the maternal line.
      Little is still known of the origins and causes of truly sporadic tumors, and the
      role of oxygen in the relationships between high-altitude, familial and truly
      sporadic paragangliomas remains to be elucidated.

PMID- 21082269
TI  - Gallstone ileus: correlation between computed tomography, double-balloon
      enteroscopy and intra-operative findings.
AB  - Gallstone ileus is an uncommon cause of small bowel obstruction, affecting mainly
      elderly patients. We report a case of gallstone ileus in an 88-year old female
      patient. The correlation between computed tomography, double-balloon enteroscopy
      and intra-operative findings is discussed, as well as treatment strategies.

PMID- 21082270
TI  - Health, self-regulation of bodily signals and intelligence: review and
      hypothesis.
AB  - Childhood IQ and adult morbidity and mortality are known to be linked even beyond
      socioeconomic variables. Yet, their interrelations are insufficiently understood.
      It has been suggested that bodily sensations play a fundamental role in health
      related self-regulation and that intelligence can influence the information
      processing of these somatic signals. This assumption is supported by reports on
      the influence of IQ on the exteroceptive (e.g. visual and auditory) and
      interoceptive (e.g. autonomic nervous system and posture) perception and
      processing of somatic information. Based on these findings the hypothesis of
      Psychosomatic Intelligence (PI) is introduced as an additional conceptual
      framework to probe the link between childhood IQ and adult health status. It
      implies a specific cognitive ability concerning the perception, interpretation,
      and self-regulation of bodily sensations. In this model, somatic signals are
      considered to reflect both intra-individual processes and individual-environment
      interactions. Based on this hypothesis the influence of intelligence on cognitive
      efforts to self-regulate somatic phenomena is amenable to systematic testing.

PMID- 21082271
TI  - Antifibrotic activity of coumarins from Cnidium monnieri fruits in HSC-T6 hepatic
      stellate cells.
AB  - The CHCl(3) fraction of Cnidium monnieri fruits significantly inhibited the
      proliferation of hepatic stellate cells in an in-vitro assay system employing HSC
      T6 hepatic stellate cell lines. Activity-guided fractionation of the CHCl(3)
      fraction of C. monnieri led to the isolation of ten coumarins: osthol (1),
      meranzin (2), auraptenol (3), meranzin hydrate (4), 7-hydroxy-8-methoxy coumarin
      (5), imperatorin (6), xanthotoxol (7), xanthotoxin (8), bergapten (9) and
      isopimpinellin (10). Of these, compounds 1 and 6 significantly inhibited
      proliferation of HSCs in a time- and concentration-dependent manner. In addition,
      compounds 1 and 6 significantly reduced collagen content in HSC-T6 cells.

PMID- 21082272
TI  - Rubus suavissimus S. Lee extract increases early adipogenesis in 3T3-L1
      preadipocytes.
AB  - Leaves of Rubus suavissimus S. Lee (Rosaceae) are used to prepare tiencha or
      sweet tea, which is helpful for body weight control by restricting calorie intake
      in obese patients. Obesity is a risk factor for metabolic syndrome, and a
      possible approach to treatment is to promote early adipogenesis in adipose
      tissue, thereby leading to replacement of enlarged adipocytes that secrete
      inflammatory factors with small adipocytes.We therefore investigated the effect
      of extract of tiencha leaves on early adipogenesis by using 3T3-L1 preadipocytes
      as a model. Tiencha extract significantly and concentration-dependently increased
      adipogenesis measured in terms of lipid accumulation by means of Oil Red O assay
      and increased the expression of adiponectin and leptin. In the early phase of
      adipogenesis, tiencha extract increased the mRNA expression of adipogenic
      transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and
      proliferator-activated receptor gamma (PPARgamma). In contrast, mRNA expression
      of other adipogenic transcription factors, C/EBPdelta and C/EBPbeta, was
      unaffected. The mRNA expression levels of adipocyte-specific genes encoding
      adipocyte protein 2 (aP2), lipoprotein lipase (LPL), and glucose transporter 4
      (Glut4), which are regulated by C/EBPalpha and PPARgamma, were also increased. A
      PPARgamma inhibitor, GW9662, partially inhibited the enhancing effect of tiencha
      extract on lipogenesis. These results suggest that tiencha extract enhances early
      adipogenesis by increasing the expression of adipogenic transcription factors
      C/EBPalpha and PPARgamma.

PMID- 21082273
TI  - A three-dimensional finite element model of the cervical spine: an investigation
      of whiplash injury.
AB  - Very few finite element models of the cervical spine have been developed to
      investigate internal stress on the soft tissues under whiplash loading situation.
      In the present work, an approach was used to generate a finite element model of
      the head (C0), the vertebrae (C1-T1) and their soft tissues. The global
      acceleration and displacement, the neck injury criterion (NIC), segmental
      angulations and stress of soft tissues from the model were investigated and
      compared with published data under whiplash loading. The calculated acceleration
      and displacement agreed well with the volunteer experimental data. The peak NIC
      was lower than the proposed threshold. The cervical S- and C-shaped curves were
      predicted based on the rotational angles. The highest segmental angle and maximum
      stress of discs mainly occurred at C7-T1. Greater stress was located in the
      anterior and posterior regions of the discs. For the ligaments, peak stress was
      at anterior longitudinal ligaments. Each level of soft tissues experienced the
      greatest stress at the time of cervical S- and C-shaped curves. The cervical
      spine was likely at risk of hyperextension injuries during whiplash loading. The
      model included more anatomical details compared to previous studies and provided
      an understanding of whiplash injuries.

PMID- 21082274
TI  - The evolution of virulence in RNA viruses under a competition-colonization trade
      off.
AB  - RNA viruses exist in large intra-host populations which display great genotypic
      and phenotypic diversity. We analyze a model of viral competition between two
      viruses infecting a constantly replenished cell pool. We assume a trade-off
      between the ability of the virus to colonize new cells (cell killing rate or
      virulence) and its local competitiveness (replicative success within coinfected
      cells). We characterize the conditions that allow for viral spread by means of
      the basic reproductive number and show that a local coexistence equilibrium
      exists, which is asymptotically stable. At this equilibrium, the less virulent
      competitor has a reproductive advantage over the more virulent colonizer
      reflected by a larger equilibrium population size of the competitor. The
      equilibria at which one virus outcompetes the other one are unstable, i.e., a
      second virus is always able to permanently invade. We generalize the two-virus
      model to multiple viral strains, each displaying a different virulence. To
      account for the large phenotypic diversity in viral populations, we consider a
      continuous spectrum of virulences and present a continuum limit of this multiple
      viral strains model that describes the time evolution of an initial continuous
      distribution of virulence without mutations. We provide a proof of the existence
      of solutions of the model equations, analytically assess the properties of
      stationary solutions, and present numerical approximations of solutions for
      different initial distributions. Our simulations suggest that initial continuous
      distributions of virulence evolve toward a distribution that is extremely skewed
      in favor of competitors. At equilibrium, only the least virulent part of the
      population survives. The discrepancy of this finding in the continuum limit with
      the two-virus model is attributed to the skewed equilibrium subpopulation sizes
      and to the transition to a continuum. Consequently, in viral quasispecies with
      high virulence diversity, the model predicts collective virulence attenuation.
      This result may contribute to understanding virulence attenuation, which has been
      reported in several experimental studies.

PMID- 21082275
TI  - Adenosquamous versus adenocarcinoma of the pancreas: a population-based outcomes
      analysis.
AB  - BACKGROUND: Pancreatic adenosquamous carcinoma has historically been
      characterized as having a more aggressive clinical course than ductal
      adenocarcinoma. The natural history of this disease, however, is essentially
      unknown. METHODS: We evaluated the clinical characteristics of all patients with
      pancreatic adenosquamous carcinoma recorded in the California Cancer Registry
      2000-2007 and compared them to those of patients with ductal adenocarcinoma.
      RESULTS: Ninety-five patients with pancreatic adenosquamous carcinoma and 14,746
      patients with ductal adenocarcinoma were identified. Demographics were similar
      between subtypes (p > 0.05). Disease stage at presentation was also similar; over
      50% of each diagnostic group presented with metastatic disease (p = 0.62).
      Surgical resection was more common among patients with locoregional adenosquamous
      carcinoma than adenocarcinoma (p = 0.0004), but rates of adjuvant therapy
      administration were similar (p > 0.05). The cohorts' median overall survival
      durations were similar in a Cox proportional hazards model (p = 0.45); overall
      survival was also similar when only patients with resected disease were
      considered (p = 0.65). Early stage, resection and receipt of radiation or
      chemotherapy were favorable independent prognostic factors among patients with
      adenosquamous carcinoma. The median overall survival duration of patients with
      resected adenosquamous carcinoma was 12 months (95% CI, 8-52). CONCLUSIONS:
      Adenosquamous carcinoma has a natural history similar to that of ductal
      adenocarcinoma when treated with prevalent clinical patterns of care.

PMID- 21082276
TI  - Mechanisms of action of the gasotransmitter hydrogen sulfide in modulating
      contractile activity of longitudinal muscle of rat ileum.
AB  - AIM: This study aims to determine mechanisms of action of the gasotransmitter
      hydrogen sulfide (H(2)S) on contractile activity in longitudinal muscle of rat
      ileum. METHODS: Ileal longitudinal muscle strips were prepared to measure
      isometric contractions. Effects of sodium hydrosulfide (NaHS), a donor of H(2)S,
      were evaluated on spontaneous contractile activity and after enhanced contractile
      activity with bethanechol. L-cysteine was evaluated as a potential endogenous
      donor of H(2)S. We evaluated involvement of extrinsic nerves, enteric nervous
      system, visceral afferent nerves, nitric oxide, and K(ATP)(+) channel and
      K(Ca)(+) channel activity on the action of H(2)S using non-adrenergic/non
      cholinergic conditions, tetrodotoxin, capsaicin, L-N(G)-nitro arginine (L-NNA),
      glibenclamide, and apamin, respectively, as well as electrical field stimulation.
      RESULT: NaHS dose-dependently and reversibly inhibited spontaneous and
      bethanechol-stimulated contractile activity (p < 0.05). L-cysteine had no
      inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin,
      capsaicin, L-NNA, glibenclamide, or apamin had no major effect on total
      contractile activity by NaHS, although both tetrodotoxin and apamin decreased the
      frequency of bethanechol-enhanced contractile activity (p < 0.05). We could not
      demonstrate H(2)S release by electrical field stimulation but did show that
      inhibition of cystathionine beta synthase, an endogenous source of H(2)S,
      augmented the inhibitory effect of low-frequency electrical field stimulation.
      CONCLUSION: H(2)S inhibits contractile activity of ileal longitudinal muscle dose
      dependently but not through pathways mediated by the extrinsic or enteric nervous
      system, visceral afferent nerves, nitric oxide, K(ATP)(+) channels, or K(Ca)(+)
      channels.

PMID- 21082277
TI  - Selection for EGFR gene amplification in a breast epithelial cell line with basal
      like phenotype and hereditary background.
AB  - An epithelial cell line, referred to as A163, was established from breast
      carcinoma derived from a patient with a strong family history of breast cancer
      but no known breast cancer susceptibility mutation. A163 was propagated in a
      serum-free culture medium including the epidermal growth factor. Immunophenotypic
      characterization demonstrated a mixed luminal and basal-like phenotype. When
      epidermal growth factor was excluded from the culture medium, A163 entered a
      quiescent period followed by a period of increased cell proliferation in a
      subpopulation of the cells. The epidermal growth factor-independent subpopulation
      retained the basal-like phenotype of the parental cell line. Karyotype and
      fluorescent in situ hybridization analysis showed an amplification of epidermal
      growth factor receptor on 7q in A163-S1 only, resulting in high expression of
      total and phosphorylated epidermal growth factor receptor. The A163-S1 sub-line
      piles up in culture, indicating a loss of contact inhibition. When grown on
      transwell filters, A163 shows basal expression of P63 and cytokeratin 14, whereas
      A163-S1 expresses P63 ubiquitously, and has lost the basal specific expression of
      cytokeratin 14, indicating a loss of polarity. Furthermore, when cultured in
      reconstituted basement membrane matrix, A163 form polarized normal like acini. In
      contrast, A163-S1 form large disorganized structures with lack of polarity. These
      cell lines may prove useful to understand molecular changes in breast cancer
      progression, in particular basal-like breast cancer subtype with bad prognosis
      and no current treatment options.

PMID- 21082278
TI  - Tagging of functional ribosomes in living cells by HaloTag(r) technology.
AB  - Ribosomal proteins and ribosomal associated proteins are complicated subjects to
      target and study because of their high conservation through evolution which led
      to highly structured and regulated proteins. Tagging of ribosomal proteins may
      allow following of protein synthesis in vivo and isolating translated mRNAs.
      HaloTag(r) is a new technology which allows detection in living cells,
      biochemical purification, and localization studies. In the present work, we
      tested HaloTag(r)-based ribosomal tagging. We focused on eIF6 (eukaryotic
      Initiation Factor 6 free 60S ribosomal marker), RACK1 (Receptor for Activated C
      Kinase 1; 40S and polysomes, not nuclear), and rpS9 (40S ribosomes, both in the
      nucleus and in the cytoplasm). Experiments performed on HEK293 cells included
      ribosomal profiles and Western blot on the fractions, purification of HaloTag(r)
      proteins, and fluorescence with time-lapse microscopy. We show that tagged
      proteins can be incorporated on ribosomes and followed by time-lapse microscopy.
      eIF6 properly accumulates in the nucleolus, and it is redistributed upon
      actinomycin D treatment. RACK1 shows a specific cytoplasmic localization, whereas
      rpS9 is both nucleolar and cytoplasmic. However, efficiency of purification
      varies due to steric hindrances. In addition, the level of overexpression and
      degradation may vary upon different constructs. In summary, HaloTag(r) technology
      is highly suitable to ribosome tagging, but requires prior characterization for
      each construct.

PMID- 21082279
TI  - The H9C2 cell line and primary neonatal cardiomyocyte cells show similar
      hypertrophic responses in vitro.
AB  - Cardiac hypertrophy is a major risk factor for heart failure and associated
      patient morbidity and mortality. Research investigating the aberrant molecular
      processes that occur during cardiac hypertrophy uses primary cardiomyocytes from
      neonatal rat hearts as the standard experimental in vitro system. In addition,
      some studies make use of the H9C2 rat cardiomyoblast cell line, which has the
      advantage of being an animal-free alternative; however, the extent to which H9C2
      cells can accurately mimic the hypertrophic responses of primary cardiac myocytes
      has not yet been fully established. To address this limitation, we have directly
      compared the hypertrophic responses of H9C2 cells with those of primary rat
      neonatal cardiomyocytes following stimulation with hypertrophic factors. Primary
      rat neonatal cardiomyocytes and H9C2 cells were cultured in vitro and treated
      with angiotensin II and endothelin-1 to promote hypertrophic responses. An
      increase in cellular footprint combined with rearrangement of cytoskeleton and
      induction of foetal heart genes were directly compared in both cell types using
      microscopy and real-time rtPCR. H9C2 cells showed almost identical hypertrophic
      responses to those observed in primary cardiomyocytes. This finding validates the
      importance of H9C2 cells as a model for in vitro studies of cardiac hypertrophy
      and supports current work with human cardiomyocyte cell lines for prospective
      molecular studies in heart development and disease.

PMID- 21082280
TI  - Hepatocyte growth factor and keratinocyte growth factor enhance IL-1-induced IL-8
      secretion through different mechanisms in Caco-2 epithelial cells.
AB  - A variety of cytokines have been detected in inflamed intestinal mucosal tissues,
      including the pro-inflammatory cytokine, interleukin-1 (IL-1), along with growth
      factors involved in wound healing processes such as proliferation and cell
      migration. However, little is known about how IL-1 and growth factors interact
      with intestinal epithelial cells to regulate the production of inflammatory
      cytokines such as interleukin-8 (IL-8). Previously, we have shown that hepatocyte
      growth factor (HGF) could significantly enhance IL-1-stimulated IL-8 secretion by
      the Caco-2 colonic epithelial cell line, yet HGF, by itself, did not stimulate IL
      8 secretion. In this report, a second growth factor, keratinocyte growth factor
      (KGF), was also found to significantly enhance IL-1-induced IL-8 secretion by
      Caco-2 cells, yet KGF, by itself, also had no effect. Simultaneous addition of
      both IL-1 and KGF was also required for the enhancing effect. Treatment of the
      Caco-2 cells with wortmannin or triciribine suppressed the enhancing effect of
      HGF, suggesting that the effect was mediated by signaling through
      phosphatidylinositol-3-kinase (PI3K) and the kinase AKT. The enhancing effect of
      KGF was not affected by wortmannin, but was suppressed by triciribine, suggesting
      that the effect of KGF was through a PI3K-independent activation of AKT. These
      results suggest that the growth factors HGF and KGF may play a role in enhancing
      IL-1-stimulated production of IL-8 by epithelial cells during mucosal
      inflammations. However, the mechanism by which the growth factors enhance the IL
      1 response may be through different initial signaling pathways.

PMID- 21082281
TI  - The effects of platelet-rich plasma derived from human umbilical cord blood on
      the osteogenic differentiation of human dental stem cells.
AB  - Platelet-rich plasma (PRP) is an emerging therapeutic application because PRP
      contains various growth factors that have beneficial effects on tissue
      regeneration and engineering. Mesenchymal stem cells and PRP derived from
      peripheral blood have been well studied. In this study, we investigated the
      effects of PRP derived from human umbilical cord blood (UCB-PRP) on
      proliferation, alkaline phosphatase (ALP) activity, and osteogenic
      differentiation of stem cells from human exfoliated deciduous teeth (SHEDs),
      dental pulp stem cells (DPSCs), and periodontal ligament stem cells (PDLSCs).
      Three types of dental stem cells were primarily isolated and characterized by
      flow cytometric analysis. Dental stem cells were exposed to various
      concentrations of UCB-PRP, which resulted in the proliferation of dental stem
      cells. Treatment with 2% UCB-PRP resulted in the highest level of proliferation.
      The ALP activity of DPSCs and PDLSCs increased following treatment with UCB-PRP
      in a dose-dependent manner up to a concentration of 2%. ALP activity decreased
      with higher concentration of UCB-PRP. The effects of UCB-PRP on calcium
      deposition were similar to those on proliferation and ALP activity. Treatment
      with 2% UCB-PRP resulted in the highest calcium depositions in DPSCs and PDLSCs;
      however, treatment with 1% UCB-PRP resulted in the highest calcium deposition in
      SHEDs. The concentrations of platelet-derived growth factor-AB and transforming
      growth factor-beta1 in UCB-PRP were investigated and found to be comparable to
      the amounts in peripheral blood. Overall, UCB-PRP had beneficial effects on the
      proliferation and osteogenic differentiation of dental stem cells. Determination
      of the optimal concentration of UCB-PRP requires further investigation for
      clinical applications.

PMID- 21082282
TI  - Two-staged nuclear transfer can enhance the developmental ability of goat-sheep
      interspecies nuclear transfer embryos in vitro.
AB  - The technique of interspecies somatic cell nuclear transfer, in which
      interspecies cloned embryos can be reconstructed by using domestic animal oocytes
      as nuclear recipients and endangered animal or human somatic cells as nuclear
      donors, can afford more opportunities in endangered animal rescue and human
      tissue transplantation, but the application of this technique is limited by
      extremely low efficiency which may be attributed to donor nucleus not fully
      reprogrammed by xenogenic cytoplasm. In this study, goat fetal fibroblasts (GFFs)
      were used as nuclear donors, in vitro-matured sheep oocytes were used as nuclear
      recipients, and a two-stage nuclear transfer procedure was performed to improve
      the developmental ability of goat-sheep interspecies clone embryos. In the first
      stage nuclear transfer (FSNT), GFFs were injected into the ooplasm of enucleated
      sheep metaphase-II oocytes, then non-activated reconstructed embryos were
      cultured in vitro, so that the donor nucleus could be exposed to the ooplasm for
      a period of time. Subsequently, in the second stage nuclear transfer, FSNT
      derived non-activated reconstructed embryo was centrifuged, and the donor nucleus
      was then transferred into another freshly enucleated sheep oocyte. Compared with
      the one-stage nuclear transfer, two-stage nuclear transfer could significantly
      enhance the blastocyst rate of goat-sheep interspecies clone embryos, and this
      result indicated that longtime exposure to xenogenic ooplasm benefits the donor
      nucleus to be reprogrammed. The two-stage nuclear transfer procedure has two
      advantages, one is that the donor nucleus can be exposed to the ooplasm for a
      long time, the other is that the problem of oocyte aging can be solved.

PMID- 21082283
TI  - Induction of enamel matrix protein expression in an ameloblast cell line co
      cultured with a mesenchymal cell line in vitro.
AB  - Interactions between epithelium and mesenchyme are important for organ and tissue
      development. In this study, in order to mimic interactions between epithelium and
      mesenchyme during native tooth development, we constructed three-dimensional
      culture systems in vitro using a collagen membrane. Two types of collagen
      membrane-based in vitro culture systems were constructed in which dental
      epithelial and dental follicle cell lines were cultured. One co-culture method
      involved inoculation of one cell line into one side of the collagen membrane, and
      the other cell line into the opposite side of the membrane (sandwich co-culture).
      As a control, the second method involved culture of one of the cell lines on a
      culture dish and the second cell line on a collagen membrane, facing away from
      the first cell line (separate co-culture). The HAT-7 cells were also grown as a
      monolayer culture on collagen. Ameloblast differentiation in these cultures was
      investigated by analysis of the mRNA and/or protein expression of ameloblastin
      and amelogenin. Our results suggest that interaction of epithelial and
      mesenchymal cells via the extracellular matrix is important for tooth
      differentiation in vitro. Our culture system should be a useful method for
      investigation of epithelial-mesenchymal interactions.

PMID- 21082284
TI  - Effects of hyperoxia on transdifferentiation of primary cultured typeII alveolar
      epithelial cells from premature rats.
AB  - Hyperoxia exposure is a significant risk factor for the impaired alveolarization
      characteristic of bronchopulmonary dysplasia. Type II alveolar epithelial cells
      (AECIIs) may serve as "alveolar stem cells" to transdifferentiate into type I
      alveolar epithelial cells (AECIs). Here, we show that hyperoxia is capable of
      inducing transdifferentiation of AECIIs in premature rats in vitro. Hyperoxia
      induced transdifferentiation was characterized by typical morphological changes,
      inhibition of cellular proliferation, decline in expression rate of Ki67,
      accumulation of cells in the G(1) phase of the cell cycle, increased expression
      of AECI-specific protein aquaporin 5, and decreased expression of AECII
      associated protein surfactant protein C. These results suggest that hyperoxia may
      induce transdifferentiation of AECIIs into AECIs and the transdifferentiation may
      be responsible for repairing early lung injury.

PMID- 21082286
TI  - De novo emerged stemness signatures in epithelial monolayers developed from
      extirpated palleal buds.
AB  - In botryllid ascidians, astogeny is executed through blastogenesis, a weekly,
      highly synchronized phenomenon of growth and death cycles, each constitutes four
      major developmental stages (A-D), operating simultaneously on three coexisting
      asexually derived generations, including primary and secondary palleal buds. This
      study documents the de novo expression of Piwi transcript and protein in
      extirpated blastogenic stage "D" buds isolated from Botryllus schlosseri colonies
      that are maintained in vitro, days after the disappearance of corresponding
      intact zooids in control colonies. Under in vitro conditions, floating buds
      attach to substrates and develop monolayers of epithelial sheets that live for
      long periods (compared to intact colonial buds) prior to their deterioration.
      Here, we further demonstrate that various cell types within floating blastogenic
      stage "D" buds are labeled as Piwi +, as do other cells that are dispersed over
      the epithelial sheets (that are Piwi -), representing highly differentiated
      state), all revealing a surprising new flag for stemness in these tissue
      fragments that developed exclusively under in vitro conditions. No single
      permanent cell-line is currently available from colonial tunicates or from other
      marine invertebrates, since cells stop dividing in vitro within 24-72 h after
      their isolation and start cellular quiescence. The development of epithelial
      sheets from isolated Botryllus palleal buds and the recorded molecular stemness
      flag of various cells, remaining for long periods under in vitro conditions, may
      pave the way for establishing cell cultures from Botryllus epithelial cells.

PMID- 21082285
TI  - Hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract against
      carbon tetrachloride-induced hepatocyte damage in Cyprinus carpio.
AB  - The present study aims to evaluate the hepatoprotective and antioxidant effects
      of Hibiscus sabdariffa extract on the carbon tetrachloride (CCl(4))-induced
      hepatocyte damage in fish and provide evidence as to whether it can be
      potentially used as a medicine for liver diseases in aquaculture. H. sabdariffa
      extract (100, 200, and 400 MUg/mL) was added to the carp primary hepatocyte
      culture before (pre-treatment), after (post-treatment), and both before and after
      (pre- and post-treatment) the incubation of the hepatocytes with CCl(4). CCl(4)
      at 8 mM in the culture medium produced significantly elevated levels of lactate
      dehydrogenase (LDH), glutamate oxalate transaminase (GOT), glutamate pyruvate
      transaminase (GPT), and malondialdehyde (MDA) and significantly reduced levels of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Pre-treatment and
      pre- and post-treatment of the hepatocytes with H. sabdariffa extract
      significantly reduced the elevated levels of LDH, GOT, GPT, and MDA and increased
      the reduced activities of SOD and GSH-Px in a dose-dependent manner; post
      treatment did not show any protective effect. The results suggest that H.
      sabdariffa extract can be potentially used for preventing rather than curing
      liver diseases in fish.

PMID- 21082287
TI  - Differentiating of banked human umbilical cord blood-derived mesenchymal stem
      cells into insulin-secreting cells.
AB  - Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are multipotent
      cells. They are able to differentiate into functional cells from not only
      mesoderm but also endoderm. Many researches showed that cells derived from fresh
      human UCB could transdifferentiate into insulin-secreting cells. In this study,
      transdifferentiating potential of cryopreserved human UCB-derived MSCs into
      insulin-secreting cell was investigated. Fresh human UCB was enriched the
      mononuclear cells by Ficoll-Paque centrifugation. The mononuclear cell population
      was cryopreserved in cryo-medium containing Iscove's modified Dulbecco's media
      (IMDM) with 10% DMSO at -196 degrees C for 1 yr. After thawing, mononuclear cells
      were cultured to isolate MSCs in medium IMDM with 20% FBS supplemented with
      growth factors. At the fifth passages, MSCs were confirmed by flow cytometry
      about expression of CD13, CD14, CD34, CD45, CD166, and HLA-DR markers; after
      that, they were induced to differentiate into adipocytes and osteoblasts. After
      inducing with specific medium for islet differentiation, there were many clusters
      of cell like islet at day 14-28. Using real-time reverse transcription polymerase
      chain reaction (RT-PCR) to analyze the expression of functional genes, the result
      showed that Nestin, Pdx-1, Ngn3, Ils-1, Pax6, Pax4, Nkx2.2, Nkx6.1, Glut-2,
      Insulin genes expressed. The results showed that MSCs derived from banked cord
      blood can differentiate into functional pancreatic islet-like cells in vitro. If
      human MSCs, especially MSCs from banked cord blood of diabetes patients
      themselves can be isolated, proliferated, differentiated into functional
      pancreatic islet-like cells, and transplanted back into them (autologous
      transplantation), their high-proliferation potency and rejection avoidance will
      provide one promising therapy for diabetes.

PMID- 21082288
TI  - Development and partial characterization of new marine cell line from brain of
      Asian sea bass Lates calcarifer for virus isolation.
AB  - A new cell line, Asian sea bass brain (ASBB), was derived from the brain tissue
      of Asian sea bass Lates calcarifer. This cell line was maintained in Leibovitz L
      15 media supplemented with 10% fetal bovine serum (FBS). The ASBB cell line was
      subcultured more than 60 times over a period of 15 mo. The ASBB cell line
      consists predominantly of fibroblastic-like cells and was able to grow at
      temperatures between 20 degrees C and 30 degrees C with an optimum temperature of
      25 degrees C. The growth rate of these cells increased as the proportion of FBS
      increased from 2% to 20% at 25 degrees C with optimum growth at the
      concentrations of 10% or 15% FBS. Polymerase chain reaction products were
      obtained from ASBB cells and tissues of sea bass with primer sets of
      microsatellite markers of sea bass. An isolate of piscine nodavirus from
      juveniles of marine fish species tested positive by IQ2000 kit for viral nervous
      necrosis detection and was examined for its infectivity to a fish cell line of
      ASBB. A marine fish betanodavirus was tested to determine the susceptibility of
      this new cell line in comparison with commercial highly permissive SSN-1 cells.
      The ASBB cell line was found to be susceptible to nodavirus (RGNNV genotype), and
      the infection was confirmed by comparison cytopathic effect (CPE) with commercial
      SSN-1 and reverse transcriptase-polymerase chain reaction. A nodavirus was
      further elucidated by electron microscopy, and the virus tested was shown to
      induce CPE on ASBB cells with significant high titer. This suggests that the ASBB
      cell line has good potential for the isolation of fish viruses.

PMID- 21082289
TI  - Smaller staple height for circular stapled gastrojejunostomy in laparoscopic
      gastric bypass: early results in 1,074 morbidly obese patients.
AB  - BACKGROUND: Anastomotic leaks, stenosis, and bleeding from the gastrojejunal
      anastomosis (GJA) after gastric bypass may carry high morbidity and mortality. To
      date, the standard operation with the circular stapler (CS) used the 25 mm with a
      staple height of 4.8 mm. We present herein our experience with the 3.5-mm staple
      height. METHODS: A total of 1,074 morbidly obese patients who underwent fully
      stapled laparoscopic Roux-en-Y Gastric Bypass over a period of 18 months were
      included in the study. Mean body mass index was 41.9 (range 28.6-70.7). Mean age
      was 40.9 years (range 15-74 years). Mean operating time was 73 min (range 43-210
      min) and the mean length of stay was 4.2 days (range 1-25 days). The 30-day
      complication rate associated with GJA was prospectively analyzed. RESULTS: Twenty
      patients (1.86%) developed postoperative bleeding. Four developed GJA bleeding
      (0.37%). One leak was recorded from the vertical staple line of the gastric
      pouch, but no leaks from the GJA were seen. Conversion to open approach was
      required in two patients (0.18%). Reoperation and readmission rates were 1.7% and
      1.8%, respectively. Perioperative complications were observed in 34 patients
      (3.1%). One case of clinical GJA stenosis was detected in a mean follow-up of
      10.5 months (range 5-20 months). There was no mortality in our series.
      CONCLUSION: Compared to our previous experience with 4.8 mm CS, creating the GJA
      using a smaller staple height significantly reduced the bleeding rate and seems
      to be a safe technique that potentially reduces other complications related to
      the GJA as reported in the literature.

PMID- 21082290
TI  - GIP and bariatric surgery.
AB  - Bariatric surgery is the most effective modality of achieving weight loss as well
      as the most effective treatment for type 2 diabetes mellitus (T2DM). Glucose
      dependent insulinotropic polypeptide (GIP) is an incretin and is implicated in
      the pathogenesis of obesity and T2DM. Its role in weight loss and resolution of
      T2DM after bariatric surgery is very controversial. We have made an attempt to
      review the physiology of GIP and its role in weight loss and resolution of T2DM
      after bariatric surgery. We searched PubMed and included all relevant original
      articles (both human and animal) in the review. Whereas most human studies have
      shown a decrease in GIP post-malabsorptive bariatric surgery, the role of GIP in
      bariatric surgery done in animal experiments remains inconclusive.

PMID- 21082291
TI  - Tako-tsubo cardiomyopathy: is there a preferred time of onset?
AB  - The occurrence of major cardiovascular events is not randomly distributed over
      time, but exhibits chronobiological patterns, i.e., circadian, weekly, or
      seasonal. No systematic studies on the temporal preference of onset of Tako-tsubo
      cardiomyopathy (TTC) are known. We performed a computer-assisted search of the
      literature (from 2000 to January 2010), with the following search terms:
      transient left ventricular apical ballooning syndrome, takotsubo-like left
      ventricular dysfunction, ampulla cardiomyopathy, tako-tsubo or takotsubo
      cardiomyopathy, tako-tsubo, apical ballooning. Criteria for publication inclusion
      were (a) reporting of original data, (b) inclusion of at least 30 or more cases,
      (c) adherence to the requested diagnostic criteria for TTC. We focused on studies
      including in their purposes the "time of onset" of events. Out of the 19 studies
      found, 7 (4 from Europe, 1 each from Asia, Australia and USA) specifically
      addressed this aspect. A circadian (morning) and a seasonal (summer) higher
      frequency of events was found. TTC seems to exhibit a temporal variation of
      onset, with preferred peaks during morning and summer. Stress and catecholamines,
      also according to their temporal organization, might play a pivotal role. The
      demonstration of time frames characterized by highest frequency of occurrence
      might help to try to ensure maximal protection during particularly vulnerable
      periods.

PMID- 21082292
TI  - Low molecular weight heparin (parnaparin) for cardioembolic events prevention in
      patients with atrial fibrillation undergoing elective electrical cardioversion: a
      prospective cohort study.
AB  - Systemic thromboembolism is a severe complication in patients undergoing
      electrical cardioversion (ECV) for atrial fibrillation (AF). Vitamin K
      antagonists greatly reduce the risk of thromboembolic events, but the
      administration scheme before ECV is troublesome as difficulties in reaching and
      maintaining the target therapeutic range for 3 weeks often delay the restoration
      and likelihood of maintaining sinus rhythm. Low molecular weight heparins (LMWHs)
      do not need dose adjustment, and may be preferable in this clinical setting. In
      this multicentre study, the LMWH parnaparin was used at a dose of 85 anti-factor
      Xa U/kg b.i.d. 2 weeks before and 3 weeks after ECV of AF. In an intention to
      treat analysis of 102 patients, there was no systemic thromboembolism or major
      bleeding (0%, 95% CI 0-3.6). Two clinically relevant non-major bleeds (2.5%, 95%
      CI 0.7-8.8) and three minor bleeds (3.8%, 95% CI 1.3-10.6) were recorded. No
      heparin-induced thrombocytopenia or other major adverse events were recorded.
      Parnaparin appears effective and safe for thromboprophylaxis of elective ECV in
      patients with AF.

PMID- 21082293
TI  - Primary clear cell adenocarcinoma of the lung.
AB  - Primary clear cell adenocarcinoma of the lung is extremely rare. A 63-year-old
      Japanese man consulted to our hospital because of cough and sputum. Imaging
      modalities including XP, CT and MRI revealed a tumor of the right middle lobe.
      They did not identify other tumors in the body. Because clinical cytology and
      biopsy showed malignant cells, segmentectomy of the lobe was performed. Grossly,
      the tumor was whitish tan tumor measuring 5 * 6 * 5 cm. Histologically, the tumor
      was composed entirely of clear cells arranged in papillary and tubular patterns.
      The tumor cells had hyperchromatic nuclei, and mitotic figure and nuclear
      stratification were scattered. Histochemically, glycogen and mucins were absent
      in tumor cell cytoplasm. Immunohistochemically, the tumor cells were positive for
      pancytokeratin (AE1/3, CAM5.2), cytokeratin (CK) 7, CK 8, CK18, CK19, EMA, CEA,
      CA19-9, CA125, p53, Ki-67 (labeling = 80%), TTF-1 and surfactant apoprotein A. In
      contrast, the tumor cells were negative for CK5/6, CK 34betaE12, CK 14, CK 20,
      vimentin, desmin, S100 protein, alpha-smooth muscle actin, AFP, HMB45, CD10,
      CD34, HER2/neu, CD56, p63, and synaptophysin. The tumor recurred 6 months after
      the operation, and right middle lobectomy was performed. Postoperative imaging
      modalities showed no tumors. The patient is alive free from tumor 9 years after
      the first manifestation.

PMID- 21082294
TI  - Tumor profiling: development of prognostic and predictive factors to guide brain
      tumor treatment.
AB  - Primary brain tumors are a heterogeneous group of malignancies with highly
      variable outcomes, and diagnosis is largely based on the histological appearance
      of the tumors. However, the diversity of primary brain tumors has made prognostic
      determinations based purely on clinicopathologic variables difficult. There is an
      increasing body of data suggesting a significant amount of molecular diversity
      accounts for the heterogeneity of clinical observations, such as response to
      treatment and time to progression. The last decade has witnessed an explosive
      advance in our knowledge of the molecular genetics of brain tumors, due in large
      part to the availability of high-throughput profiling techniques and to the
      completion of the human genome sequencing project. The large amount of data
      generated by these efforts has enabled the identification of prognostic and
      predictive factors and helping to identify pathways which are driving tumor
      growth. Identification of biomarkers will enable better patient stratification
      and individualization of treatment.

PMID- 21082295
TI  - Dyslexic children show deficits in implicit sequence learning, but not in
      explicit sequence learning or contextual cueing.
AB  - Dyslexia is a specific learning disability characterized by difficulties with
      accurate and/or fluent word recognition and by poor spelling abilities. The
      absence of other high level cognitive deficits in the dyslexic population has led
      some authors to propose that non-strategical processes like implicit learning
      could be impaired in this population. Most studies have addressed this issue by
      using sequence learning tasks, but so far the results have not been conclusive.
      We test this hypothesis by comparing the performance of dyslexic children and
      good readers in both implicit and explicit versions of the sequence learning
      task, as well as in another implicit learning task not involving sequential
      information. The results showed that dyslexic children failed to learn the
      sequence when they were not informed about its presence (implicit condition). In
      contrast, they learned without significant differences in relation to the good
      readers group when they were encouraged to discover the sequence and to use it in
      order to improve their performance (explicit condition). Moreover, we observed
      that this implicit learning deficit was not extended to other forms of non
      sequential, implicit learning such as contextual cueing. In this case, both
      groups showed similar implicit learning about the information provided by the
      visual context. These results help to clarify previous contradictory data, and
      they are discussed in relation to how the implicit sequence learning deficit
      could contribute to the understanding of dyslexia.

PMID- 21082296
TI  - Response to the case report by Mattar: Generic Imatinib (Imatib, Cipla) in a
      patient with chronic myeloid leukemia in chronic phase.

PMID- 21082297
TI  - Single photon emission computed tomography (SPECT) techniques for
      resynchronization: phase analysis and equilibrium radionuclide angiocardiography.

PMID- 21082298
TI  - Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson
      pharmacologic stress: rationale and design of a prospective, randomized,
      multicenter study.
AB  - BACKGROUND: Caffeine attenuates the coronary hyperemic response to adenosine by
      competitive A2(A) receptor blockade. This study aims to determine whether oral
      caffeine administration compromises diagnostic accuracy in patients undergoing
      vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a
      selective adenosine A(2A) agonist. METHODS: This multicenter, randomized, double
      blind, placebo-controlled, parallel-group study includes patients with suspected
      coronary artery disease who regularly consume caffeine. Each participant
      undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson
      stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with
      double-blind administration of oral caffeine 200 or 400 mg or placebo capsules
      (MPI-3; n = 90 per arm). Only participants with >= 1 reversible defect on the
      second MPI study undergo the subsequent stress MPI test. The primary endpoint is
      the difference in the number of reversible defects on the two stress tests using
      a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the
      effect of caffeine on the regadenoson exposure-response relationship. Safety will
      also be assessed. CONCLUSION: The results of this study will show whether the
      consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study
      with regadenoson affects the diagnostic validity of stress testing
      (ClinicalTrials.gov number, NCT00826280).

PMID- 21082299
TI  - Prevalence and predictors of mechanical dyssynchrony as defined by phase analysis
      in patients with left ventricular dysfunction undergoing gated SPECT myocardial
      perfusion imaging.
AB  - BACKGROUND: A novel method to quantify dyssynchrony using phase analysis of
      single-photon emission computed tomography (SPECT) myocardial perfusion imaging
      has been developed. We sought to determine the prevalence of SPECT-derived
      mechanical dyssynchrony, and we report clinical variables which predict
      mechanical dyssynchrony in patients with left ventricular dysfunction. METHODS:
      We used a count-based Fourier analysis method to convert the regional myocardial
      counts from discrete frames per cardiac cycle into a continuous thickening
      function which allows resolution of the phase of the onset of myocardial
      contraction. The standard deviation of left ventricular phases (Phase SD)
      describes the regional phase dispersion as a measure of dyssynchrony. Significant
      dyssynchrony was defined as Phase SD >= 43 degrees . 260 patients with left
      ventricular ejection fraction <= 35% were examined. RESULTS: The prevalence of
      mechanical dyssynchrony in the entire cohort of patients studied was 52%.
      Univariate predictors of Phase SD were age (P = .03), black race (P = .0005), QRS
      duration, EF, EDV, summed stress score (SSS), and summed rest score (SRS) (all P
      = <.0001). Black race, male gender, QRS EF, and SRS were independent predictors
      of SPECT-based mechanical dyssynchrony. CONCLUSIONS: Significant SPECT-based
      mechanical dyssynchrony is relatively common among patients with left ventricular
      dysfunction. In a population of patients with predominantly ischemic heart
      disease referred for SPECT, a reduced EF, increasing QRS duration, severity and
      extent of myocardial scar on SPECT imaging are independent predictors of
      mechanical dyssynchrony and may serve to identify patients for dyssynchrony
      screening.

PMID- 21082300
TI  - Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology.
AB  - With the rapid growth of molecular biology, in vivo imaging of such molecular
      process (i.e., molecular imaging) has been well developed. The molecular imaging
      has been focused on justifying advanced treatments and for assessing the
      treatment effects. Most of molecular imaging has been developed using PET camera
      and suitable PET radiopharmaceuticals. However, this technique cannot be widely
      available and we need alternative approach. 123I-labeled compounds have been also
      suitable for molecular imaging using single-photon computed tomography (SPECT)
      123I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity
      of heart failure and prognosis. In addition, it has a potential role to predict
      fatal arrhythmia, particularly for those who had and are planned to receive
      implantable cardioverter-defibrillator treatment. 123I-beta-methyl
      iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying
      ischemia at rest, based on the unique capability to represent persistent
      metabolic alteration after recovery of ischemia, so called ischemic memory. Since
      BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it
      may permit risk analysis in CAD patients, particularly for those with chronic
      kidney disease and/or hemodialysis patients. This review will discuss about
      recent development of these important iodinated compounds.

PMID- 21082301
TI  - Flavin-containing monooxygenase mRNA levels are up-regulated in als brain areas
      in SOD1-mutant mice.
AB  - Flavin-containing monooxygenases (FMOs) are a family of microsomal enzymes
      involved in the oxygenation of a variety of nucleophilic heteroatom-containing
      xenobiotics. Recent results have pointed to a relation between Amyotrophic
      Lateral Sclerosis (ALS) and FMO genes. ALS is an adult-onset, progressive, and
      fatal neurodegenerative disease. We have compared FMO mRNA expression in the
      control mouse strain C57BL/6J and in a SOD1-mutated (G93A) ALS mouse model. Fmo
      expression was examined in total brain, and in subregions including cerebellum,
      cerebral hemisphere, brainstem, and spinal cord of control and SOD1-mutated mice.
      We have also considered expression in male and female mice because FMO regulation
      is gender-related. Real-Time TaqMan PCR was used for FMO expression analysis.
      Normalization was done using hypoxanthine-guanine phosphoribosyl transferase
      (Hprt) as a control housekeeping gene. Fmo genes, except Fmo3, were detectably
      expressed in the central nervous system of both control and ALS model mice. FMO
      expression was generally greater in the ALS mouse model than in control mice,
      with the highest increase in Fmo1 expression in spinal cord and brainstem. In
      addition, we showed greater Fmo expression in males than in female mice in the
      ALS model. The expression of Fmo1 mRNA correlated with Sod1 mRNA expression in
      pathologic brain areas. We hypothesize that alteration of FMO gene expression is
      a consequence of the pathological environment linked to oxidative stress related
      to mutated SOD1.

PMID- 21082302
TI  - Contribution of orthodontic load to inflammation-mediated periodontal
      destruction.
AB  - AIM: Orthodontic malpractice as well as hyperocclusal forces can aggravate
      periodontitis-induced destruction of tooth-supporting tissues, but the underlying
      mechanisms for the co-destructive effect of biomechanical loading are yet to be
      elucidated. This in-vitro study was performed to investigate whether
      biomechanical forces modulate the response of periodontal ligament (PDL) cells to
      inflammation. MATERIALS AND METHODS: PDL cells (from six donors) grown on
      BioFlex((r)) plates were treated with interleukin (IL) 1beta, which is increased
      at inflamed periodontal sites, and/or subjected to cyclic tensile strain (CTS) of
      low (3%) and high (20%) magnitudes for 1beta and 6 d. The synthesis of
      proinflammatory mediators (IL1beta, IL8, COX2), growth factors (IGF1, VEGF,
      TGFbeta1), collagen type 1 (COL1) and osteogenic proteins (ALP, RUNX2) was
      analyzed by real-time PCR and ELISA. The wound fill rate was examined in an in
      vitro wound healing assay. For statistical analyses, Student's t-test and ANOVA
      were applied (p<0.05). RESULTS: In general, the IL1beta-induced expression of
      proinflammatory mediators was significantly enhanced by CTS on day 1 and
      significantly downregulated on day 6. CTS of high magnitude significantly
      inhibited the IGF1 synthesis but significantly upregulated VEGF under normal and
      inflammatory conditions. In general, CTS also downregulated the IL1beta-induced
      COL1, ALP, and RUNX2 expression. From day 5 on, the lowest wound fill rate was
      observed in cells which were simultaneously exposed to inflammatory and
      biomechanical signals. CONCLUSION: These findings suggest that orthodontic and
      occlusal loading may contribute to periodontal destruction in periodontally
      diseased patients through downregulation of matrix and osteogenic proteins but
      not via augmentation of periodontal inflammation.

PMID- 21082303
TI  - Precision of an instrumentation-based method of analyzing occlusion and its
      resulting distribution of forces in the dental arch.
AB  - BACKGROUND AND OBJECTIVE: In practice, analysis of occlusion is reduced to
      depicting it with color-marking foils. Precise analysis that incorporates time
      resolution and plots the distribution of forces within the occlusion is not
      possible in the everyday clinical situation with the usual methods. T-Scan((r))
      III is a computer-assisted dental occlusion analyzer that depicts occlusion by
      means of pressure-sensitive foils. The aim of our study was to test the accuracy
      and reliability of this method. SUBJECTS AND METHODS: The study population
      comprised 42 subjects (23 male and 19 female, aged 20-30, median age 26 years).
      The measurements were performed using the TScan((r)) III from Tekscan Inc., South
      Boston, MA, USA. Six recordings with two foils were made for each subject and a
      total of 30 masticatory cycles were registered. Statistical analysis referred to
      the method's measurement accuracy and reliability, as well as the influence of
      changing the foil and repositioning the T-Scan((r)) III during the repeated
      measurements. RESULTS: The percentage distribution of forces per tooth ranged
      from 0 to 41%. The mean measurement per tooth was 6.9% of the maximum total force
      exerted. The measurement error was 1%, the 1.96-fold measurement error calculated
      according to Bland & Altman (accuracy) was 2% and the 2.77-fold measurement error
      (reliability) was 2.8%. Neither changing the foil nor the repeated measuring had
      any statistically significant influences on the measured value. CONCLUSION: The
      measuring technique studied is superior to the usual methods, particularly with
      regard to force analysis per tooth. The level of accuracy is acceptable and no
      interference arising from change of foil or repeated measuring was detected. The
      method presented in this study therefore enhances routine diagnostics with
      marking foils. A combination of this method with marking foils would be ideal
      because the pressure-sensitive foils in this system do not produce any contact
      markings intraorally. This combination enables the contacts depicted on the
      computer to be assigned intraorally with even greater precision.

PMID- 21082304
TI  - Influence of enamel conditioning on the shear bond strength of different
      adhesives.
AB  - BACKGROUND AND OBJECTIVE: Phosphoric acid etching is the gold standard for enamel
      conditioning. However, it is possible that air abrasion or a combination of air
      abrasion and etching might result in enhanced adhesion. The aim of this study was
      to investigate the effect of different enamel conditioning methods on the bond
      strength of six adhesives. MATERIAL AND METHODS: Three different enamel
      conditioning procedures (phosphoric acid etching, air abrasion, air abrasion +
      phosphoric acid etching) were evaluated for their influence on the shear bond
      strength of six different adhesives (TransbondTM XT, Cool-BondTM, Fuji Ortho LC,
      Ultra Band-Lok, Tetric((r)) Flow, Light-BondTM). Each group consisted of 15
      specimens. Shear forces were measured with a universal testing machine. The
      scores of the Adhesive Remnant Index (ARI) were also analyzed. RESULTS: There
      were no significant differences between phosphoric acid etching and air abrasion
      + phosphoric acid etching. Air abrasion as a single conditioning technique led to
      significantly lower shear forces. The ARI scores did not correlate with the shear
      strengths measured. There were greater variations in shear forces for the
      different adhesives than for the conditioning techniques. CONCLUSION: The highest
      shear forces were found for the conventional composites TransbondTM XT and Cool-
      BondTM in combination with conventional etching. Air abrasion alone and in
      combination with phosphoric acid etching showed no advantages compared with
      phosphoric acid etching alone and, therefore, cannot be recommended.

PMID- 21082305
TI  - 3D analysis of condylar position after sagittal split osteotomy of the mandible
      in mono- and bimaxillary orthognathic surgery - a methodology study in 18
      patients.
AB  - OBJECTIVES: This study analyzes the condylar position with intercondylar distance
      and angle after sagittal split osteotomy in mono- and bimaxillary orthognathic
      surgery applying cone-beam computed tomography (CBCT) images before and after
      surgery. MATERIALS AND METHODS: Data of 18 patients, ten males (mean age 28
      years) and eight females (mean age 26 years) undergoing the described surgery
      between 2008 and 2009 were analyzed. CBCT scans were performed with the KaVo
      3DeXam (KaVo, Biberach/ Ribeta, Germany) (identical with the iCAT scan device)
      before and after surgery. The exported DICOM data were analyzed with ImageJ
      morphometry software. Patients were also asked about TMJ problems. The two-tailed
      t test was used and significance was set at a p value less than p = 0.05.
      RESULTS: There was no significant difference between the pre- and postoperative
      distances between condylar centers (mean difference: 1 mm) (p = 0.69) and
      intercondylar angle (mean difference: 6.6 degrees ) (p = 0.27). CONCLUSIONS: CBCT
      is a novel imaging technique appropriate for detailed and three-dimensional
      analysis of the condylar position in orthognathic surgery. Available freeware
      analysis software can be applied for metrical measurements. Our cases showed no
      significant changes of condylar position immediately after surgery without
      intraoperative condylar fixation.

PMID- 21082306
TI  - Halitosis, oral health and quality of life during treatment with Invisalign((r))
      and the effect of a low-dose chlorhexidine solution.
AB  - AIM: This study examined how halitosis, oral dryness and general oral health were
      impacted during treatment with the Invisalign((r)) system. Furthermore, the
      effect of a lowdose chlorhexidine solution (CHX) was evaluated. PATIENTS AND
      METHODS: Thirtyone patients with good periodontal health participated in this
      crossover study and were divided into two groups (group 1: CHX/no CHX, group 2:
      no CHX/CHX). The following parameters were recorded during the first 8 months of
      Invisalign((r)) treatment: stimulated saliva flow rate, organoleptic index,
      tongue coating index, measurement of the oral volatile sulfur compound level
      (ppb), modified gingival and plaque index and bleeding on probing index.
      Professional oral cleaning was performed at the beginning of each period lasting
      3 months. The patients received a questionnaire at the first, third, fourth,
      sixth and eighth control visits. RESULTS: The very low volatile sulfur compound
      level was significantly decreased by CHX (0.06%) during the first examination
      period (p = 0.02), i.e. for the first group of patients only. Neither halitosis,
      nor oral dryness, nor high plaque or gingival index measurements were observed.
      Oral health-related quality of life was hardly influenced by wearing aligners and
      oral hygiene habits were very good. CONCLUSIONS: This study provides evidence
      that Invisalign((r)) treatment is characterized by only minimal impairment of
      overall oral health and the associated quality of life. Consequently, it appears
      unnecessary to recommend the general adjunctive use of a low-dose chlorhexidine
      mouthwash during treatment with Invisalign((r)).

PMID- 21082307
TI  - Late infiltration of post-orthodontic white spot lesions.
AB  - White spot lesion (WSL) infiltration has been recommended immediately after
      debonding of orthodontic brackets. It is however not clear if established
      inactive WSLs can also be masked through infiltration. Orthodontic treatment of a
      19-year-old patient had to be terminated prematurely due to development of
      multiple WSLs of varying severity. Three months after debonding, the patient
      presented for lesion infiltration. After etching with 15% HCl gel and re-wetting
      of the dried surfaces it seemed that a good outcome could be expected. Lesion
      infiltration led to complete masking of less severe WSLs. The visual appearance
      of moderate and severe WSLs was improved but they were still visible after
      treatment. Inactive WSLs may not represent an increased caries risk, but patients
      are often bothered esthetically. Infiltration by repeated etching might be a
      viable approach even for inactive WSLs. Controlled clinical trials are needed to
      investigate the long-term performance of this technique.

PMID- 21082308
TI  - Advanced microscopy of microbial cells.
AB  - Growing awareness of heterogeneity in cells of microbial populations has
      emphasized the importance of advanced microscopy for visualization and
      understanding of the molecular mechanisms underlying cell-to-cell variation. In
      this review, we highlight some of the recent advances in confocal microscopy,
      super-resolution optical microscopy (STED, SIM, PALM) as well as atomic force
      microscopy and Raman spectroscopy. Using examples of bistability in microbial
      populations as well as biofilm development and differentiation in bacterial and
      yeast consortia, we demonstrate the importance of microscopy for visualization of
      variation between cells in phenotypic traits such as gene expression.

PMID- 21082309
TI  - Colutea arborescens is nodulated by diverse rhizobia in Eastern Morocco.
AB  - Eighteen isolates of rhizobia isolated from root nodules of Colutea arborescens
      (Bladder senna) grown in different soils of the eastern area of Morocco were
      characterized by phenotypic and genomic analyses. All the isolates characterized
      were fast growers. This is may be due to the isolation procedures used. The
      phenotypic, symbiotic and cultural characteristics analyzed allowed the
      description of a wide physiological diversity among tested isolates. The results
      obtained suggest that the phenotype of these rhizobia might have convergent
      evolved to adapt the local conditions. The genetic characterization consisted in
      an analysis of the rep-PCR fingerprints and the PCR-based RFLP of the 16S rDNA
      patterns. The 16S rDNA of six isolates representing the main ribotypes obtained
      by the PCR-based RFLP was sequenced. A large diversity was observed among these
      rhizobia, and they were classified as different species of the genera Rhizobium,
      Sinorhizobium and Mesorhizobium. The nodC gene was also sequenced, and the
      results confirmed the three lineages corresponding to the three genera. The
      results of the sequencing of nodC and 16S rDNA genes suggest that the nodulation
      genes and chromosome might have co-evolved among these bacteria.

PMID- 21082311
TI  - The role of the medial longitudinal fasciculus in horizontal gaze: tests of
      current hypotheses for saccade-vergence interactions.
AB  - Rapid shifts of the point of visual fixation between equidistant targets require
      equal-sized saccades of each eye. The brainstem medial longitudinal fasciculus
      (MLF) plays a cardinal role in ensuring that horizontal saccades between
      equidistant targets are tightly yoked. Lesions of the MLF--internuclear
      ophthalmoparesis (INO)--cause horizontal saccades to become disjunctive:
      adducting saccades are slow, small, or absent. However, in INO, convergence
      movements may remain intact. We studied horizontal gaze shifts between
      equidistant targets and between far and near targets aligned on the visual axis
      of one eye (Muller test paradigm) in five cases of INO and five control subjects.
      We estimated the saccadic component of each movement by measuring peak velocity
      and peak acceleration. We tested whether the ratio of the saccadic component of
      the adducting/abducting eyes stayed constant or changed for the two types of
      saccades. For saccades made by control subjects between equidistant targets, the
      group mean ratio (+/-SD) of adducting/abducting peak velocity was 0.96 +/- 0.07
      and adducting/abducting peak acceleration was 0.94 +/- 0.09. Corresponding ratios
      for INO cases were 0.45 +/- 0.10 for peak velocity and 0.27 +/- 0.11 for peak
      acceleration, reflecting reduced saccadic pulses for adduction. For control
      subjects, during the Muller paradigm, the adducting/abducting ratio was 1.25 +/-
      0.14 for peak velocity and 1.03 +/- 0.12 for peak acceleration. Corresponding
      ratios for INO cases were 0.82 +/- 0.18 for peak velocity and 0.48 +/- 0.13 for
      peak acceleration. When adducting/abducting ratios during Muller versus
      equidistant targets paradigms were compared, INO cases showed larger relative
      increases for both peak velocity and peak acceleration compared with control
      subjects. Comparison of similar-sized movements during the two test paradigms
      indicated that whereas INO patients could decrease peak velocity of their
      abducting eye during the Muller paradigm, they were unable to modulate adducting
      velocity in response to viewing conditions. However, the initial component of
      each eye's movement was similar in both cases, possibly reflecting activation of
      saccadic burst neurons. These findings support the hypothesis that horizontal
      saccades are governed by disjunctive signals, preceded by an initial, high
      acceleration conjugate transient and followed by a slower vergence component.

PMID- 21082310
TI  - Suboptimal online control of aiming movements in virtual contexts.
AB  - We determined whether uncertainty about the location of one's hand in virtual
      environments limits the efficacy of online control processes. In the Non-aligned
      and Aligned conditions, the participant's hand was represented by a cursor on a
      vertical or horizontal display, respectively. In the Natural condition,
      participants saw their hand. During an acquisition phase, visual feedback was
      either permitted or not during movement execution. To test the hypothesis (Norris
      et al. 2001) that reliance on visual feedback increases as the task becomes less
      natural (Natural < Aligned < Non-aligned), following acquisition, participants
      performed a transfer phase without visual feedback. During acquisition in both
      visual feedback conditions, movement endpoint variability increased as the task
      became less natural. This suggests that the orientation of the display and the
      representation of one's hand by a cursor introduced uncertainty about its
      location, which limits the efficacy of online control processes. In contradiction
      with the hypothesis of Norris et al. (2001), withdrawing visual feedback in
      transfer had a larger deleterious effect on movement accuracy as the task became
      less natural. This suggests that the CNS increases the weight attributed to the
      input that can be processed without first having to be transformed.

PMID- 21082312
TI  - Muscarinic inhibition of recurrent glutamatergic excitation in frog tectum column
      prevents NMDA receptor activation on efferent neuron.
AB  - It is widely recognized that neuronal network activity can be modulated via
      activation of nicotinic and muscarinic acetylcholine receptors located pre- and
      postsynaptically. It was established in our earlier study that the activation of
      presynaptic nicotinic receptors greatly facilitates the retinotectal
      glutamatergic transmission. In the present study, we have determined a
      transmitter of tectal recurrent excitation and explored the effects of muscarinic
      acetylcholine receptor activation on the recurrent excitation and the activity of
      frog tectum column in vivo. Discharge of a single retinal ganglion cell was
      elicited by a minimal electrical stimulation of the retina. Evoked activity of
      the tectum column was recorded using the carbon-fiber microelectrode inserted
      into the tectum layer F. We found the following: 1. The recurrent excitation in
      the tectum column was not affected by d-tubocurarine (10 MUM) and was greatly
      depressed by the kynurenic acid (500 MUM), demonstrating glutamatergic nature of
      the recurrent excitation. 2. The glutamatergic recurrent excitation was largely
      reduced by carbamylcholine (100 MUM) and oxotremorine-M (10 MUM), demonstrating
      that the activation of muscarinic receptors, located, presumably, on the
      presynaptic terminals of recurrent pear-shaped neurons, inhibits the recurrent
      excitation in the tectum column. 3. The muscarinic inhibition of glutamatergic
      recurrent transmission had critical influence on the activity of the tectum
      column, preventing the generation of an output signal through suppression of the
      NMDA receptor activation and establishing necessary conditions for returning of
      the network to its resting state.

PMID- 21082313
TI  - The development of grasping comprehension in infancy: covert shifts of attention
      caused by referential actions.
AB  - An eye tracking paradigm was used to investigate how infants' attention is
      modulated by observed goal-directed manual grasping actions. In Experiment 1, we
      presented 3-, 5-, and 7-month-old infants with a static picture of a grasping
      hand, followed by a target appearing at a location either congruent or
      incongruent with the grasping direction of the hand. The latency of infants gaze
      shift from the hand to the target was recorded and compared between congruent and
      incongruent trials. Results demonstrate a congruency effect from 5 months of age.
      A second experiment illustrated that the congruency effect of Experiment 1 does
      not extend to a visually similar mechanical claw (instead of the grasping hand).
      Together these two experiments describe the onset of covert attention shifts in
      response to manual actions and relate these findings to the onset of manual
      grasping.

PMID- 21082314
TI  - Alterations in human motor cortex during dual motor task by transcranial magnetic
      stimulation study.
AB  - The aim of this study was to determine how and whether changes in the primary
      motor cortex (M1) are affected by dual motor task. We further investigated how
      dual motor task is dependent on task properties measured using transcranial
      magnetic stimulation (TMS). TMS delivered to left M1 during the dual motor task
      and motor-evoked potential (MEP) were simultaneously evoked in the right FDI,
      thenar, FCR and ECR muscles. In experiment 1, subjects were asked to
      simultaneously walk on a treadmill and perform finger prehension. The gait
      conditions were employed 30, 50 and 80% of maximum walking speed (gait 30%, gait
      50% and gait 80%). Conditions for finger prehension while following the visual
      tracking task varied with force outputs of 5 and 25% of maximum voluntary
      contraction (MVC). In experiment 2, the subjects were asked to perform optimal
      walking synchronized with the finger prehension task with an optimal walking
      rhythm (2-Hz dual motor task), as well as optimal walking desynchronized with the
      finger prehension task (0.7-Hz dual motor task). In experiment 1, MEPs were
      markedly decreased under the gait 50% condition compared with those under the
      gait 30 and 80% conditions at 5% MVC. In experiment 2, MEPs were markedly
      decreased with the 2-Hz dual motor task compared with those with the 0.7-Hz dual
      motor task. Our results suggest that the excitability changes in M1 during the
      dual motor task were dependent on changes in the gait speed, precision of
      prehension task and temporal movement.

PMID- 21082316
TI  - Microbial transformation of pharmaceuticals naproxen, bisoprolol, and diclofenac
      in aerobic and anaerobic environments.
AB  - Although biotransformation is generally considered to be the main process by
      which to remove pharmaceuticals, both in sewage treatment plants and in aquatic
      environments, quantitative information on specific compounds is scarce. In this
      study, the transformations of diclofenac (DCF), naproxen (NPX), and bisoprolol
      (BSP) were studied under aerobic and anaerobic conditions using inocula taken
      from activated and digested sludge processes, respectively. Whereas concentration
      decays were monitored by LC-tandem mass spectrometry, oxygen consumption and
      methane production were used for the evaluation of the performance of overall
      conditions. DCF was recalcitrant against both aerobic and anaerobic
      biotransformation. More than one third of the BSP disappeared under aerobic
      conditions, whereas only 14% was anaerobically biotransformed in 161 days. Under
      aerobic conditions, complete removal of NPX was evident within 14 days, but
      anaerobic transformation was also efficient. Formation of 6-O-desmethylnaproxen,
      a previously reported aerobic metabolite, was also detected under anaerobic
      conditions and persisted for 161 days.

PMID- 21082315
TI  - Impaired conflict monitoring in Parkinson's disease patients during an oculomotor
      redirect task.
AB  - Fallibility is inherent in human cognition and so a system that will monitor
      performance is indispensable. While behavioral evidence for such a system derives
      from the finding that subjects slow down after trials that are likely to produce
      errors, the neural and behavioral characterization that enables such control is
      incomplete. Here, we report a specific role for dopamine/basal ganglia in
      response conflict by accessing deficits in performance monitoring in patients
      with Parkinson's disease. To characterize such a deficit, we used a modification
      of the oculomotor countermanding task to show that slowing down of responses that
      generate robust response conflict, and not post-error per se, is deficient in
      Parkinson's disease patients. Poor performance adjustment could be either due to
      impaired ability to slow RT subsequent to conflicts or due to impaired response
      conflict recognition. If the latter hypothesis was true, then PD subjects should
      show evidence of impaired error detection/correction, which was found to be the
      case. These results make a strong case for impaired performance monitoring in
      Parkinson's patients.

PMID- 21082317
TI  - Trophic transfer of lead through a model marine four-level food chain:
      Tetraselmis suecica, Artemia franciscana, Litopenaeus vannamei, and Haemulon
      scudderi.
AB  - The objective of this investigation was to assess the transfer of lead (Pb) along
      an experimental, four-level food chain: Tetraselmis suecica (phytoplankton) ->
      Artemia franciscana (crustacean, brine shrimp) -> Litopenaeus vannamei
      (crustacean, white shrimp) -> Haemulon scudderi (fish, grunt). T. suecica was
      exposed to a sublethal dose of Pb in solution and then used as the base of a
      marine food chain. Significant differences in Pb concentrations were found
      between exposed organisms of the different trophic levels and the control.
      Particularly, Pb concentrations in fish of the simulated trophic chain were two
      to three times higher in the exposed specimens than in the control. Levels of Pb
      in phytoplankton showed a substantial increase with respect to the solution
      (level I), with bioconcentration factors averaging from 930 to 3630. In contrast,
      a strong decrease in Pb concentration from phytoplankton to zooplankton (level
      II) and from zooplankton to shrimp tissues (level III) was evidenced by
      bioaccumulation factors <1. Despite the decrease in the assimilation efficiency
      of metal transfer observed in these two predators, Pb concentration in the grunt
      fish (level IV) was higher than in the shrimp (level III) (bioaccumulation factor
      >1.0). Some of the added Pb is transferred from the phytoplankton along the food
      chain, thus producing a net accumulation of Pb mainly in fish and, to a lesser
      extent, in shrimp tissues. Because Pb is one of the most pervasive contaminants
      in coastal ecosystems, its transference by way of diet and potential net
      accumulation in higher predators is of ecologic importance for marine life. In
      addition, because shrimp and adult Haemulon scudderi are commercially important
      resources, this issue is of particular relevance to the safety of marine
      products.

PMID- 21082320
TI  - Plasma cluster ions decrease the antigenicity of mite allergens and suppress
      atopic dermatitis in NC/Nga mice.
AB  - Mite antigens play important roles in the pathogenesis of atopic dermatitis (AD).
      We recently developed a novel air cleaner (KC-850U) using charged plasma cluster
      ions to eliminate a variety of allergens from house environments. The present
      work demonstrates the ability of KC-850U to decrease the symptoms of AD induced
      by mite allergens. Pooled sera from the conventional NC/Nga mice, and AD model
      animals, were incubated with varying concentrations of the control and KC-850U
      pretreated allergens extracted from mite. The incubated mixtures were transferred
      to wells coated with intact allergens and subjected to ELISA to measure the
      amounts of immunoglobulin E (IgE) bound to the wells. Kinetic analysis revealed
      that exposure of mite extracts to plasma cluster ions destructed about 95% of the
      epitopes of the allergens. The specific pathogen-free and conventional mice were
      housed in rooms equipped with either KC-850U or a standard air cleaner and
      observed their dermal symptom for 2 weeks. Dermatological examination revealed
      the AD symptom of the conventional mice housed in a room equipped with an air
      cleaner. In contrast, the symptoms which became apparent during the experiments
      were suppressed remarkably exposing mice to plasma cluster ions. These
      observations suggested that plasma cluster ions generated by KC-850U destroyed
      the epitopes of mite allergens and suppressed the symptoms of AD in the mice.

PMID- 21082319
TI  - Oxidative stress in erythrocytes from patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
      inflammation. It has been suggested that the level of reactive oxygen species
      (ROS) in patients with RA is higher than in healthy subjects. The aim of the
      present study was to investigate the level of the lipid peroxidation, antioxidant
      enzyme activities (CAT, SOD, GSH-Px), level of the -SH groups and GSH and
      Na(+)K(+) ATPase activity in erythrocytes from patients with RA. There are no
      significant differences in CAT and GSH-Px activities. SOD activity is lower in RA
      patients than in the control group. Increase in the lipid peroxidation is
      observed in RA patients. Levels of the GHS and -SH groups are significantly lower
      in RA patients than in the control groups. Total ATPase and Na(+)K(+) ATPase
      activities decrease in RA patients.

PMID- 21082321
TI  - Brainstem and spinal cord involvement in a paraneoplastic syndrome associated
      with anti-Yo antibody and breast cancer.

PMID- 21082323
TI  - Late-stage Parkinson's disease in the Lisbon-Barcelona cohorts: past
      phenomenology and today's clinical needs.

PMID- 21082322
TI  - Management of respiratory symptoms in ALS.
AB  - Respiratory insufficiency is a frequent feature of ALS and is present in almost
      all cases at some stage of the illness. It is the commonest cause of death in
      ALS. FVC is used as important endpoint in many clinical trials, and in decision
      making events for patients with ALS, although there are limitations to its
      predictive utility. There are multiple causes of respiratory muscle failure, all
      of which act to produce a progressive decline in pulmonary function.
      Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness,
      lead to reduced lung compliance and atelectasis. Increased secretions increase
      the risk of aspiration pneumonia, which further compromises respiratory function.
      Bulbar dysfunction can lead to nutritional deficiency, which in turn increases
      the fatigue of respiratory muscles. Early recognition of respiratory decline and
      symptomatic intervention, including non-invasive ventilation can significantly
      enhance both quality of life and life expectancy in ALS. Patients with
      respiratory failure should be advised to consider an advance directive to avoid
      emergency mechanical ventilation.

PMID- 21082324
TI  - Spontaneous pain, pain threshold, and pain tolerance in Parkinson's disease.
AB  - The mechanisms underlying pain in Parkinson's disease (PD) are unclear. Although
      a few studies have reported that PD patients may have low pain threshold and
      tolerance, none could accurately assess whether there was a correlation between
      sensory thresholds and demographic/clinical features of PD patients. Thus,
      tactile threshold, pain threshold, and pain tolerance to electrical stimuli in
      the hands and feet were assessed in 106 parkinsonian patients (of whom 66
      reported chronic pain) and 51 age- and sex-matched healthy subjects. Linear
      regression models determined relationships between psychophysical parameters and
      demographic/clinical features. Female gender, severity of disease, medical
      disease associated with painful symptoms, and dyskinesia were more frequently
      observed in PD patients experiencing pain, even though dyskinesia did not reach
      significance. Pain threshold and pain tolerance were significantly lower in PD
      patients than in control subjects, whereas the tactile threshold yielded
      comparable values in both groups. Multivariable linear regression analyses
      yielded significant inverse correlations of pain threshold and pain tolerance
      with motor symptom severity and Beck depression inventory. Pain threshold and
      pain tolerance did not differ between PD patients with and without pain. In the
      former group, there was no relationship between pain threshold and the
      intensity/type of pain, and number of painful body parts. These findings suggest
      that pain threshold and pain tolerance tend to decrease as PD progresses, which
      can predispose to pain development. Female gender, dyskinesia, medical conditions
      associated with painful symptoms, and postural abnormalities secondary to
      rigidity/bradikinesia may contribute to the appearance of spontaneous pain in
      predisposed subjects.

PMID- 21082325
TI  - Molecular analysis of an additional case of hybrid sterility in rice (Oryza
      sativa L.).
AB  - Hybrid sterility hinders the exploitation of the heterosis displayed by japonica
      * indica rice hybrids. The variation in pollen semi-sterility observed among
      hybrids between the japonica recipient cultivar and each of two sets of
      chromosome segment substitution lines involving introgression from an indica
      cultivar was due to a factor on chromosome 5 known to harbor the gene S24. S24
      was fine mapped to a 42 kb segment by analyzing a large F(2) population bred from
      the cross S24-NIL * Asominori, while the semi-sterility shown by the F(1) hybrid
      was ascribable to mitotic failure at the early bicellular pollen stage.
      Interestingly, two other pollen sterility genes (f5-Du and Sb) map to the same
      region (Li et al. in Chin Sci Bull 51:675-680, 2006; Wang et al. in Theor Appl
      Genet 112:382-387, 2006), allowing a search for candidate genes in the 6.4 kb
      overlap between the three genes. By sequencing the overlapped fragment in wild
      rice, indica cultivars and japonica cultivars, a protein ankyrin-3 encoded by the
      ORF2 was identified as the molecular base for S24. A cultivar Dular was found to
      have a hybrid-sterility-neutral allele, S24-n, in which an insertion of 30 bp was
      confirmed. Thus, it was possible to add one more case of molecular bases for the
      hybrid sterility. No gamete abortion is caused on heterozygous maternal genotype
      with an impaired sequence from the hybrid-sterility-neutral genotype. This result
      will be useful in understanding of wide compatibility in rice breeding.

PMID- 21082326
TI  - Failed anterior lumbar interbody fusion due to incomplete foraminal
      decompression.
AB  - BACKGROUND: Anterior lumbar interbody fusion (ALIF) has gained widespread
      popularity for spinal disorders requiring fusion. The purpose of this study was
      to analyze ALIF failures. METHODS: The medical records of 223 patients treated
      with ALIF between January 2007 and June 2008 were retrospectively reviewed.
      Patients with unfavorable outcomes, including subsequent posterior decompression
      at the index level or poor outcomes after ALIF were identified based on clinical
      and radiological findings. The patients were divided into two groups: an
      unfavorable group and a favorable group. Preoperative clinical and radiological
      factors for each group were statistically analyzed. RESULTS: Two hundred of the
      223 patients were enrolled in this study. Thirteen (6.5%) of 200 patients
      resulted in unfavorable outcome. Four patients (2%) of them underwent posterior
      decompressive surgery. The main cause of unfavorable outcomes was incomplete
      decompression of the foraminal stenosis. Unfavorable outcomes were obtained in
      patients with the level of L5-S1 (p = 0.036), higher body mass index (p = 0.048),
      higher percentage of slippage (p = 0.024), and severe facet arthropathy (p =
      0.013). However, there was no difference in preoperative disc height, foraminal
      size, facet angle, facet tropism, or preoperative visual analog scale for back
      and leg pain, the Oswestry disability index, symptom duration, and fusion rate
      between the two groups. CONCLUSION: Based on these results, posterior
      decompression and fusion may be considered for obese patients with the level of
      L5-S1, high-grade spondylolisthesis, or severe facet arthropathy. On the other
      hand, ALIF can be used an effective alternative treatment in many spinal
      disorders requiring fusion.

PMID- 21082328
TI  - Regulation of gemma formation in the copper moss Scopelophila cataractae by
      environmental copper concentrations.
AB  - Considerable attention has recently been focused on the use of hyperaccumulator
      plants for the phytoremediation of soils contaminated with heavy metals. The
      moss, Scopelophila cataractae (Mitt.) Broth., is a typical hyperaccumulator that
      is usually observed only in copper-rich environments and which accumulates high
      concentrations of copper in its tissues. However, many of the physiological
      processes and mechanisms for metal hyperaccumulation in S. cataractae remain
      unknown. To address this issue, we examined the mechanisms regulating gemma
      formation, which is considered the main strategy by which S. cataractae relocates
      to new copper-rich areas. From this study we found that treatment of S.
      cataractae with high concentrations of copper suppressed gemma formation but
      promoted protonemal growth. The suppressive effect was not observed by treatment
      with heavy metals other than copper. These results suggest the importance of
      copper-sensitive asexual reproduction in the unique life strategy of the copper
      moss, S. cataractae.

PMID- 21082327
TI  - Sea-cod oil supplementation alters the course of Streptococcus pneumoniae
      infection in BALB/c mice.
AB  - The existing reports on the role of omega-3 polyunsaturated fatty acids (PUFA) in
      infectious diseases are contradictory. The present study was conducted to
      evaluate the effect of sea-cod oil on the course of respiratory tract infection
      by Streptococcus pneumoniae in BALB/c mice. Animals were given enteral sea-cod
      oil for a period of 30 and 60 days and challenged intra-tracheally with S.
      pneumoniae D39 serotype 2. The survival of animals and various inflammatory
      parameters, i.e. myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide (NO)
      and leukotriene B(4) in the lung homogenates, were investigated. The inflammatory
      cytokines levels (IL-1beta, TNF-alpha and IL-10) were also determined. Continuous
      sea-cod oil supplementation for 60 days significantly improved survival among the
      animals. A significant reduction in the bacterial load in the lungs of sea-cod
      oil-fed animals compared to the controls was observed. As the disease progressed,
      the reduced bacterial colonisation correlated well with the histopathological
      observation. This was accompanied by a decrease in the production of inflammatory
      mediators and cytokines in the lung homogenates. However, not even a minor
      difference was seen in animals given sea-cod oil supplementation for 30 days
      duration; therefore, long-term treatment was required to attain an effect. Sea
      cod oil supplementation modulated the host immune response and, thus, protected
      the host from ensuing inflammatory damage due to S. pneumoniae-mediated
      infection.

PMID- 21082330
TI  - Digestion of cattle manure under mesophilic and thermophilic conditions:
      characterization of organic matter applying thermal analysis and 1H NMR.
AB  - Digestion of cattle manure collected from a livestock farm together with bedding
      material (straw) has been studied under mesophilic and thermophilic conditions in
      batch reactors. The digestion was carried out for a prolonged period with the aim
      of evaluating the changes undergone by the organic matter. The mesophilic
      digestion carried out revealed a greater capacity to produce gas and transform
      organic matter, while a higher conversion rate, but a lower gas yield, was
      obtained under thermophilic conditions. Degradation of the organic matter was
      evaluated by means of thermal analysis and (1)H NMR. Stabilisation through
      anaerobic digestion (either mesophilic or thermophilic) resulted in an increase
      in the quality of the organic matter, as characterised by an enrichment in
      thermostable compounds, and an accumulation of long chain aliphatic materials.
      The experiments performed demonstrated the transformation of organic matter into
      complex materials under anaerobic conditions with an accumulation of aliphatic
      components under both types of conditions tested. Degradation through mesophilic
      digestion, in comparison to the thermophilic process, resulted in a greater
      destruction of straw particles.

PMID- 21082329
TI  - Computer-assisted combinatorial design of bicyclic thymidine analogs as
      inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.
AB  - Thymidine monophosphate kinase (TMPK(mt)) is an essential enzyme for nucleotide
      metabolism in Mycobacterium tuberculosis, and thus an attractive target for novel
      antituberculosis agents. In this work, we have explored the chemical space around
      the 2',3'-bicyclic thymidine nucleus by designing and in silico screening of a
      virtual focused library selected via structure based methods to identify more
      potent analogs endowed with favorable ADME-related properties. In all the library
      members we have exchanged the ribose ring of the template with a cyclopentane
      moiety that is less prone to enzymatic degradation. In addition, we have replaced
      the six-membered 2',3'-ring by a number of five-membered and six-membered
      heterocyclic rings containing alternative proton donor and acceptor groups, to
      exploit the interaction with the carboxylate groups of Asp9 and Asp163 as well as
      with several cationic residues present in the vicinity of the TMPK(mt) binding
      site. The three-dimensional structure of the TMPK(mt) complexed with 5
      hydroxymethyl-dUMP, an analog of dTMP, was employed to develop a QSAR model, to
      parameterize a scoring function specific for the TMPK(mt) target and to select
      analogues which display the highest predicted binding to the target. As a result,
      we identified a small highly focused combinatorial subset of bicyclic thymidine
      analogues as virtual hits that are predicted to inhibit the mycobacterial TMPK in
      the submicromolar concentration range and to display favorable ADME-related
      properties.

PMID- 21082331
TI  - Degradation of zearalenone by the extracellular extracts of Acinetobacter sp.
      SM04 liquid cultures.
AB  - A bacterium (designated SM04) which can rapidly grow on zearalenone (ZEN) as sole
      carbon and energy source was isolated from agricultural soil. On the basis of 16S
      rDNA sequencing analysis, strain SM04 was classified as a bacterium belonging to
      the Acinetobacter genus. In this study, the biodegradation of ZEN by the
      extracellular extracts of strain SM04 liquid cultures in M1 medium and Nutrient
      Broth medium was examined using HPLC analysis, APCI-MS analysis, and MTT
      (tetrazolium salt) cell proliferation assay. Results showed no ZEN and other
      equally estrogenic metabolites were found after 12 h when ZEN was treated with
      the extracellular extracts of M1 cultures, but no significant (P < 0.01)
      reduction of ZEN was observed over the 12-h incubation period in the
      extracellular extracts of Nutrient Broth cultures. Results also indicated that
      some proteins in the extracellular extracts of M1 cultures were essential to ZEN
      degradation. The proteins in the extracellular extracts of M1 cultures and
      Nutrient Broth cultures were analyzed with SDS-PAGE, bands showing different
      intensities among the two extracellular extracts were processed for protein
      identification by MALDI-TOF/TOF/MS, and nine proteins from M1 cultures matched
      the database for Acinetobacter genus with great confidence. Furthermore, the
      function of some proteins identified is unknown or unconfirmed because of the
      lack of well-annotated genomic sequence data and protein data for Acinetobacter
      genus on the public database, but in further studies these data of proteins
      identified will be useful for screening the genes related to ZEN degradation.

PMID- 21082332
TI  - Rhizoremediation of diesel-contaminated soil using the plant growth-promoting
      rhizobacterium Gordonia sp. S2RP-17.
AB  - A plant growth-promoting rhizobacterium (PGPR) was isolated and identified as
      Gordonia sp. S2RP-17, which showed ACC deaminase and siderophore synthesizing
      activities. Its maximum specific growth rate was 0.54 +/- 0.12 d(-1) at 5,000 mg
      L(-1) of total petroleum hydrocarbon (TPH), and its maximum diesel degradation
      rate was 2,434.0 +/- 124.4 mg L(-1) d(-1) at 20,000 mg L(-1) of TPH. The growth
      of Zea mays was significantly promoted by the inoculation of Gordonia sp. S2RP-17
      in the diesel-contaminated soil. Measured TPH removal efficiencies by various
      means were 13% by natural attenuation, 84.5% by planting Zea mays, and 95.8% by
      the combination of Zea mays and Gordonia sp. S2RP-17. The S2RP-17 cell counts
      were maintained at 1 * 10(6) CFU g-soil(-1) during the remediation period,
      although they slightly decreased from their initial numbers (2.94 * 10(7) CFU g
      soil(-1)). These results indicate that rhizoremediation using both Zea mays and
      Gordonia sp. S2RP-17 is a promising strategy for enhancing remediation efficiency
      of diesel-contaminated soils.

PMID- 21082333
TI  - Electrophysiological and behavioral responses of sorghum shoot fly, Atherigona
      soccata, to sorghum volatiles.
AB  - The sorghum shoot fly, Atherigona soccata, is an economically important pest of
      sorghum in Asia, Mediterranean Europe and Africa. Field observations have
      suggested that shoot fly susceptible sorghum varieties emit attractive volatiles,
      but the compounds involved were unknown. The objective of the present study was
      to identify plant-derived attractants for A. soccata. Headspace samples were
      collected from the susceptible cultivar 'Swarna,' and when female A. soccata were
      exposed to the volatiles in an olfactometer bioassay, a strong positive
      behavioral response was observed. Coupled GC-EAG with female A. soccata revealed
      eight compounds that elicited an EAG response, which were identified by coupled
      GC-MS and GC peak enhancement on two GC columns of different polarity as (Z)-3
      hexen-1-yl acetate, (-)-alpha-pinene, (-)-(E)-caryophyllene, methyl salicylate,
      octanal, decanal, 6-methyl-5-hepten-2-one and nonanal. When an eight-component
      synthetic blend of the EAG active compounds, at the same concentration (2.64 MUg)
      and ratio as in the natural headspace sample, was tested, A. soccata spent more
      time in the treated region of the olfactometer than controls (P = 0.001).
      Furthermore, when this synthetic blend and the natural headspace sample were
      tested in a choice test, the shoot flies did not show any preference for either
      of the two treatments, demonstrating that the synthetic blend had similar
      activity to the natural sample. Results are discussed in relation to breeding
      sorghum varieties less attractive to this pest.

PMID- 21082335
TI  - Dissecting dad.

PMID- 21082334
TI  - Leaf and floral parts feeding by orange tip butterfly larvae depends on larval
      position but not on glucosinolate profile or nitrogen level.
AB  - In an attempt to identify chemical signals governing the general flower and
      silique feeding behavior of larvae of the orange tip butterfly, Anthocharis
      cardamines (L.), we investigated feeding behavior and chemistry of two major host
      plants: Cardamine pratensis L. and Alliaria petiolata (Bieb.) Cavara & Grande
      (garlic mustard). Larvae reportedly feed mainly on flowers and siliques rather
      than leaves in nature, and did so when observed on the original host plants.
      Behavioral experiments, using detached A. petiolata branches, however, showed
      that larvae readily accepted leaves and only the final instar showed a tendency
      for directed movement towards floral parts. To search for semiochemicals that
      control plant part preference and to assess possible nutritional consequences of
      floral parts feeding, we determined glucosinolate profiles and total nitrogen
      levels of floral parts and leaves. There was only moderate difference between
      glucosinolate profiles of leaves and floral parts within each of two host plant
      species. In contrast, the profiles of floral parts differed significantly between
      them. A. petiolata was dominated by 2-propenyl glucosinolate, while C. pratensis
      was dominated by aromatic glucosinolates and branched aliphatic glucosinolates,
      with considerable variation among populations. Nitrogen levels tended to be
      higher in floral parts than in leaves in A. petiolata, but not in C. pratensis,
      so floral feeding could not generally be attributed to higher N content. With the
      exception of a tendency of last instar larvae (L5) to move to the apex and ingest
      flowers and upper stem, we did not find either a plant chemistry basis or larval
      acceptance/rejection behavior that could explain the usual feeding of floral
      parts by orange tip larvae of all instars. However, by artificial manipulation of
      vertical larval position on host plants, we found that the frequency of leaf vs.
      flower feeding during 24 hr depended significantly on the initial larval
      position. Hence, we suggest that the placement of eggs on floral parts by
      ovipositing female butterflies is a major explanation of orange tip feeding
      habits previously known from field observations.

PMID- 21082336
TI  - CD4+FoxP3+ regulatory T-cells in cerebral ischemic stroke.
AB  - Experimental cerebral ischemic stroke is exacerbated by inflammatory T-cells and
      is accompanied by systemic increases in CD4+CD25+Foxp3+ regulatory T-cells
      (Treg). To determine their effect on ischemic brain injury, Treg were depleted in
      Foxp3(DTR) mice prior to stroke induction. In contrast to a recent Nature
      Medicine report, our results demonstrate unequivocally that Treg depletion did
      not affect stroke infarct volume, thus failing to implicate this regulatory
      pathway in limiting stroke damage.

PMID- 21082337
TI  - Role of inducible or neuronal nitric oxide synthase in neurogenesis of the
      dentate gyrus in aged mice.
AB  - We evaluated mainly the iNOS (inducible nitric oxide synthase) and nNOS (neuronal
      NOS) expression in the subgranular zone (SGZ) of the dentate gyrus of the
      hippocampus in young adult (8-week-old) and aged (60-week-old) mice. The present
      study demonstrates that the expression of nNOS was more pronounced than that of
      iNOS expression in the dentate gyrus of aged mice. Our study also suggests that
      aged mice exhibited a significant loss of motor activity as compared with young
      adult animals. Furthermore, our results provide that no significant change in the
      number of Neu N (Neuronal nuclei)-immunopositive neurons and GFAP (glial
      fibrillary acidic protein)-immunopositive astrocytes was observed in the dentate
      gyrus between young adult and aged mice. In contrast, a significant change in the
      number of Iba 1(ionized calcium-binding adaptor molecule 1)-immunopositive
      microglia in aged mice was observed in the dentate gyrus as compared to young
      adult animals. These results provide the novel evidence showing that the
      expression of nNOS may be crucial for the role of neurogenesis of the SGZ of the
      dentate gyrus in aged mice. Furthermore, our present findings demonstrate that
      the inhibition of nNOS expression in the SGZ of the dentate gyrus during aging
      processes may offer novel therapeutic strategies for anti-aging in humans.

PMID- 21082339
TI  - The effect of partner sex: nondisclosure of HIV status to male and female
      partners among men who have sex with men and women (MSMW).
AB  - A common concern within HIV prevention is that HIV positive MSMW do not disclose
      their HIV status to female partners who are thus at increased risk for HIV
      infection. The present study uses unique data to examine whether MSMW disclose
      more often to male rather than female partners. Data were collected on most
      recent male and/or female primary partner and four most recent casual partners
      from 150 MSMW (50 African American, 50 Latino, 50 White). MSMW reported on 590
      partners (31% female; 69% male). Disclosure was coded as disclosure before sex,
      disclosure after sex, or nondisclosure. A series of multinomial logistic
      regressions with partners clustered within respondents were conducted to evaluate
      effects of respondent characteristics and partner characteristics on timing of
      disclosure. In bivariate and multivariate analyses there were no significant
      differences in odds of disclosure to male and female partners before or after
      sex. Although MSMW were substantially less likely to disclose to HIV negative
      partners before sex compared to HIV positive partners regardless of sex, when we
      fully interacted the multivariate model by partner sex, the odds of disclosure to
      HIV negative male partners compared to HIV positive male partners before sex were
      significantly higher than the odds of disclosure to HIV negative female partners
      compared to HIV positive female partners. Patterns of mutual nondisclosure and
      nonreciprocal disclosure were observed with both primary and casual partners. The
      paper makes additional methodological contributions to the measurement and
      analysis of disclosure.

PMID- 21082338
TI  - Change in sexual activity 12 months after ART initiation among HIV-positive
      Mozambicans.
AB  - We assessed sexual behaviors before and 12-months after ART initiation among 277
      Mozambicans attending an HIV clinic. Measured behaviors included the number of
      sexual partners, condom use, concurrent relationships, disclosure of HIV status,
      alcohol use, and partners' serostatus. Compared to before ART initiation,
      increases were seen 12 months after ART in the proportion of participants who
      were sexually active (48% vs. 64% respondents, P < 0.001) and the proportion of
      participants with HIV-negative or unknown serostatus partners (45% vs. 80%, P <
      0.001). Almost all (96%) concurrent partnerships reported at 12 months formed
      after ART initiation. Although reported correct and consist condom use increased,
      the number of unprotected sexual relationships remained the same (n = 45). Non
      disclosure of HIV-serostatus to sexual partners was the only significant
      predictor of practicing unprotected sex with partners of HIV-negative or unknown
      serostatus. Sexual activity among HIV-positive persons on ART increased 12 months
      after ART initiation. Ongoing secondary transmission prevention programs
      addressing sexual activity with multiple partners, disclosure to partners and
      consistent condom use with serodisconcordant partners must be incorporated
      throughout HIV care programs.

PMID- 21082340
TI  - Risk factors of alcohol problem drinking among female bar/hotel workers in Moshi,
      Tanzania: a multi-level analysis.
AB  - There is limited information on alcohol problem drinking, which has been
      associated with sexually transmitted infections (STIs), including HIV, among
      female bar/hotel workers in Africa. This paper aimed to identify the individual-
      and facility-level determinants of alcohol problem drinking in this setting.
      Problem drinking was defined based on the CAGE alcohol screening scale. Multi
      level logistic regression was used to identify individual- and facility-level
      factors associated with problem drinking. About 37.3% of women (N = 1629) were
      classified as having probable or definite problem drinking. In multi-level
      analysis, main characteristics associated with problem drinking included: having
      3-4 partners in the past 5 years compared to having 1-2, used a condom in the
      last sex comparing to non-use, history of transactional sex, having more
      pregnancies, and facilities whose employees do not live on the premises.
      Interventions which combine alcohol and sexual risk reduction counseling are
      urgently needed in this population.

PMID- 21082341
TI  - Internet use among female sex workers in China: implications for HIV/STI
      prevention.
AB  - Based on a cross-sectional survey with 1,022 female sex workers (FSWs) recruited
      from different types of commercial sex venues in Southwest China, we examined
      their Internet-using behaviors and explored the feasibility of Internet-based
      HIV/STI intervention in this population. About 75% of FSWs were Internet users;
      among them 57% were frequent users, and 40% had searched HIV/STI information
      online. Internet use was significantly associated with younger age, more
      schooling, higher income, and engagement in a social network of Internet users.
      Frequent use of the Internet was associated only with factors of the social
      environment, such as peers' Internet use. Two thirds of Internet-using FSWs were
      willing to participate in an online HIV/STI prevention program. Multivariate
      analyses showed that willingness to participate in an online HIV/STI prevention
      intervention was significantly associated with higher Internet use and younger
      age. Our data suggest that Internet may offer a promising strategy to deliver low
      cost HIV/STI prevention programs for FSWs in China.

PMID- 21082342
TI  - Detecting vegetation cover change on the summit of Cadillac Mountain using multi
      temporal remote sensing datasets: 1979, 2001, and 2007.
AB  - This study examines the efficacy of management strategies implemented in 2000 to
      reduce visitor-induced vegetation impact and enhance vegetation recovery at the
      summit loop trail on Cadillac Mountain at Acadia National Park, Maine. Using
      single-spectral high-resolution remote sensing datasets captured in 1979, 2001,
      and 2007, pre-classification change detection analysis techniques were applied to
      measure fractional vegetation cover changes between the time periods. This
      popular sub-alpine summit with low-lying vegetation and attractive granite
      outcroppings experiences dispersed visitor use away from the designated trail, so
      three pre-defined spatial scales (small, 0-30 m; medium, 0-60 m; and large, 0-90
      m) were examined in the vicinity of the summit loop trail with visitor use
      (experimental site) and a site chosen nearby in a relatively pristine undisturbed
      area (control site) with similar spatial scales. Results reveal significant
      changes in terms of rates of vegetation impact between 1979 and 2001 extending
      out to 90 m from the summit loop trail with no management at the site. No
      significant differences were detected among three spatial zones (inner, 0-30 m;
      middle, 30-60 m; and outer, 60-90 m) at the experimental site, but all were
      significantly higher rates of impact compared to similar spatial scales at the
      control site (all p < 0.001). In contrast, significant changes in rates of
      recovery between 2001 and 2007 were observed in the medium and large spatial
      scales at the experimental site under management as compared to the control site
      (all p < 0.05). Also during this later period a higher rate of recovery was
      observed in the outer zone as compared to the inner zone at the experimental site
      (p < 0.05). The overall study results suggest a trend in the desired direction
      for the site and visitor management strategies designed to reduce vegetation
      impact and enhance vegetation recovery at the summit loop trail of Cadillac
      Mountain since 2000. However, the vegetation recovery has been rather minimal and
      did not reach the level of cover observed during the 1979 time period. In
      addition, the advantages and some limitations of using remote sensing
      technologies are discussed in detecting vegetation change in this setting and
      potential application to other recreation settings.

PMID- 21082343
TI  - Using digital time-lapse cameras to monitor species-specific understorey and
      overstorey phenology in support of wildlife habitat assessment.
AB  - Critical to habitat management is the understanding of not only the location of
      animal food resources, but also the timing of their availability. Grizzly bear
      (Ursus arctos) diets, for example, shift seasonally as different vegetation
      species enter key phenological phases. In this paper, we describe the use of a
      network of seven ground-based digital camera systems to monitor understorey and
      overstorey vegetation within species-specific regions of interest. Established
      across an elevation gradient in western Alberta, Canada, the cameras collected
      true-colour (RGB) images daily from 13 April 2009 to 27 October 2009. Fourth
      order polynomials were fit to an RGB-derived index, which was then compared to
      field-based observations of phenological phases. Using linear regression to
      statistically relate the camera and field data, results indicated that 61% (r (2)
      = 0.61, df = 1, F = 14.3, p = 0.0043) of the variance observed in the field
      phenological phase data is captured by the cameras for the start of the growing
      season and 72% (r (2) = 0.72, df = 1, F = 23.09, p = 0.0009) of the variance in
      length of growing season. Based on the linear regression models, the mean
      absolute differences in residuals between predicted and observed start of growing
      season and length of growing season were 4 and 6 days, respectively. This work
      extends upon previous research by demonstrating that specific understorey and
      overstorey species can be targeted for phenological monitoring in a forested
      environment, using readily available digital camera technology and RGB-based
      vegetation indices.

PMID- 21082344
TI  - Circulating oxidative stress status in dromedary camels infested with sarcoptic
      mange.
AB  - Oxidative stress is an imbalance between radical-generating and radical
      scavenging activity, resulting in oxidation products and tissue damage. This
      study was aimed to evaluate the status of oxidative stress indices in blood of
      camels naturally infested with S. scabiei. Forty-seven male camels (Camelus
      dromedaries) were divided according to the extent of the infested area with
      Sarcoptes scabiei into four groups, mild (MID, n = 12), moderate (MOD, n = 10),
      severely infested (SEV, n = 10) and healthy control group (n = 15). Blood was
      used for determination of red cell count (RBC), hemoglobin (Hb), packed cell
      volume (PCV), serum nitric oxide (NO(*), a free radical), ascorbate and albumin
      concentrations, and erythrocytic values of malondialdehyde (MDA, a marker of
      lipid peroxidation), protein carbonyls (PC, an indicator of protein oxidation),
      glutathione (GSH) superoxide dismutase (SOD) and catalase (CAT). Decreased levels
      (P < 0.05) of RBC, Hb, PCV, albumin and ascorbate were noticed in MOD and SEV
      compared to controls with the lowest values (P < 0.05) in SEV except for
      ascorbate, where MOD did not differ from SEV. Compared to controls, NO(*)
      gradually increased (P < 0.05) in MID followed by MOD and SEV, whereas MDA and PC
      were higher (P < 0.05) in MOD and SEV. PC was higher (P < 0.05) in MOD than SEV.
      In addition, the antioxidants GSH, SOD and CAT were higher (P < 0.05) in MID and
      lower (P < 0.05) in MOD and SEV compared to controls. GSH was lower (P < 0.05) in
      SEV compared to MOD. Besides, Hb was negatively correlated with NO(*) (r = -0.68,
      P < 0.001), MDA (r = -0.53, P < 0.001) and PC (r = -0.73, P < 0.001). In
      conclusion, dromedary sarcoptosis is accompanied by a state of oxidative stress
      process, which increased by increasing the area of infestation, and may
      contribute to the pathogenesis of the disease.

PMID- 21082345
TI  - New report of parasite-fauna of the free-tailed bat (Tadarida brasiliensis,
      Geoffroy, 1824) in Chile.
AB  - One hundred and ninety five specimens of free tailed bat (Tadarida brasiliensis)
      obtained from two regions of Chile were analized to determine parasite infection.
      From those specimens the endoparasites identified were: Trematoda: Acanthatrium
      lunatum, Limatuoides limatulus and Paralecithodendrium carlsbadensis; Cestoda:
      Vampirolepis sp.; Nematoda: Nochtia pilosus and Anoplostrongylus paradoxus. The
      ectoparasites identified were Chiroptonyssus robustipes, Ewingnana inaequalis and
      Notoedres lasionycteris all of them are acari species. Even thought the bat
      specimens are from the same species on both survey sites, the results differ for
      each site when the parasite species identified are compared.

PMID- 21082346
TI  - Precut fistulotomy for difficult biliary cannulation: is it a risky preference in
      relation to the experience of an endoscopist?
AB  - BACKGROUND: Several studies have reported on the correlation between the
      experience level of an endoscopist and the outcomes of precut procedures.
      However, there are limited data on the early use of the precut fistulotomy in
      relation to the experience of an endoscopist. AIM: To evaluate the efficacy and
      safety of precut fistulotomy in difficult biliary cannulation after ERCP
      training. METHODS: Two endoscopists, one at each tertiary referral center,
      performed the precut fistulotomy for difficult biliary cannulation between
      September 2008 and February 2010. The technical success, complications, and
      clinical outcomes in three groups were recorded prospectively over time. RESULTS:
      A total of 159 (23.1%) patients underwent precut fistulotomy. The mean procedure
      time was decreased as the number of procedures increased (p < 0.01). The success
      rates of selective biliary cannulation in the three groups were 86.8, 86.8, and
      88.7% respectively, for the first attempt (p = 0.77) and 93.7% for the second
      attempt. Post-ERCP pancreatitis developed in nine (5.7%) patients, which was not
      statistically significant between the three groups. As the frequency of papillary
      contacts increased, post-ERCP pancreatitis tended to increase (p = 0.017). In the
      multivariate analysis, more than 15 attempts at cannulating the major papilla
      prior to fistulotomy was a risk factor for pancreatitis (odds ratio 4.8, 95% CI
      1.178-19.580, p = 0.029). CONCLUSIONS: After therapeutic ERCP training involving
      at least 100 ERCPs, including at least half that were therapeutic cases and more
      than ten that were precut papillotomies, a precut fistulotomy can be performed
      safely and effectively in low-risk patients.

PMID- 21082347
TI  - Survival after anatomic resection versus nonanatomic resection for hepatocellular
      carcinoma: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: To compare the effect on survival of anatomic
      resection (AR) versus nonanatomic resection (NAR) in patients with hepatocellular
      carcinoma (HCC) from all published comparative studies in the literature.
      METHODS: Databases, including Pubmed, Embase, the Cochrane Library, Ovid, and Web
      of Science, were searched to identify studies comparing AR with NAR for HCC. In
      this meta-analysis, primary end points were the overall survival and disease-free
      survival; the secondary end point was local recurrence rate. The meta-analysis
      was performed by use of RevMan 4.2. RESULTS: Nine comparative studies comprising
      1,503 patients (833 AR and 670 NAR) were identified. In the combined results,
      disease-free survival was significantly higher in the AR group than in the NAR
      group (OR 1.78, 95% CI 1.22-2.59, P = 0.003; heterogeneity P = 0.08). Overall
      survival (OR 1.31, 95% CI 0.92-1.85, P = 0.13; heterogeneity P = 0.04) did not
      suggest any significant difference between AR and NAR. No statistically
      significant difference was found for local recurrence rate between the two
      resection methods (OR 0.55, 95% CI 0.25-1.23, P = 0.15; heterogeneity P = 0.010).
      CONCLUSIONS: Anatomic resection is associated with better disease-free survival
      than nonanatomic resection. Because heterogeneity was detected, caution is needed
      in interpretation of the results. Better designed, adequately powered studies are
      required to address this issue.

PMID- 21082348
TI  - IgG4-associated cholecystitis: another clue in the diagnosis of autoimmune
      pancreatitis.
AB  - PURPOSE: Autoimmune pancreatitis (AIP) is the pancreatic manifestation of IgG4
      associated systemic disease (ISD). Criteria for diagnosis of AIP include
      recognition of extra-pancreatic organ involvement. Because the diagnosis of AIP
      can be challenging, even for experts, it is important for clinicians to recognize
      other target organ damage in this disease. Typical gallbladder findings in AIP
      have been increasingly recognized. Because cholecystectomy is common in the
      community, the availability of previous tissue from the gallbladder can provide
      an important supportive clue in the diagnosis of AIP. The objective of this
      review is to examine the literature on common gallbladder pathology findings in
      AIP, and discuss their clinical utility. RESULTS: Gallbladder involvement in AIP
      seems to be common. Transmural lymphoplasmacytic inflammatory infiltrates,
      extramural inflammatory nodules, the presence of tissue eosinophilia, phlebitis,
      and increased tissue IgG4 are all seen more frequently in the gallbladders of
      patients with AIP. These findings are not 100% specific, because some can be seen
      in primary sclerosing cholangitis and pancreatic adenocarcinoma. CONCLUSION:
      Cholecystectomy for the purpose of diagnosing AIP is not recommended. However, if
      gallbladder specimens from a previous cholecystectomy are available, an expert
      review of gallbladder slides with IgG4 immunostaining may help to provide
      additional criteria for diagnosis of autoimmune pancreatitis.

PMID- 21082349
TI  - Somatostatin methylation as a biomarker for gastric cancer: ready for "prime
      time" or for further validation?

PMID- 21082350
TI  - Incidence of esophageal carcinoma among Malays in North-Eastern Peninsular
      Malaysia: an area with an exceptionally low prevalence of Helicobacter pylori
      infection.
AB  - BACKGROUND: Obesity, gastroesophageal reflux, and Barrett's esophagus have all
      been linked to esophageal adenocarcinoma. In addition, the decline in
      Helicobacter pylori (H. pylori) infection in affluent societies has also been
      suggested to be a major factor in the recent rise in the incidence of esophageal
      adenocarcinoma. If H. pylori infection has a protective role, populations with a
      naturally low prevalence of H. pylori infection such as the ethnic Malays of
      Northeastern Peninsular Malaysia should have high rates of esophageal
      adenocarcinoma. AIM: To test this hypothesis, we investigated the incidence of
      esophageal carcinoma among the ethnic Malays of the state of Kelantan in
      Northeastern Peninsular Malaysia. METHODS: The pathology services in the state of
      Kelantan are provided by two main hospitals. The histopathological records of
      both hospitals were systematically examined to retrieve all cases of esophageal
      carcinoma diagnosed between 2004 and 2008. Incidence rates were determined based
      on the most recent population census. RESULTS: The age-standardized incidence
      rates (per 100,000 population) of esophageal adenocarcinoma among Malay men and
      women were 0.75 and 0.69, respectively. The corresponding rates for squamous cell
      carcinoma of the esophagus were 0.66 and 1.34, respectively. CONCLUSIONS: The low
      rates of adenocarcinoma and squamous cell carcinoma of the esophagus in the study
      area, despite the fact that H. pylori infection is virtually absent, does not
      support the hypothesis that the absence of H. pylori infection is a pivotal
      factor in the pathogenesis of these cancers.

PMID- 21082351
TI  - Altered expression and localization of connexin32 in human and murine gastric
      carcinogenesis.
AB  - BACKGROUND: Intercellular communication via gap junctions, composed of protein
      subunits called connexins (Cxs), plays a key role in controlling cell growth,
      differentiation and carcinogenesis. Impaired gap junctional intercellular
      communication has been reported in various cancers and diseases. AIMS: We
      investigated Cx32 expression patterns and semiquantitatively assessed Cx32
      expression in cancers and preneoplastic lesions. To determine if cell
      proliferation is correlated with Cx32 expression, we evaluated Ki67 expression in
      a gastric cancer mouse model. METHODS: In human and mouse, normal stomach and
      gastric adenocarcinoma tissues were used for immunohistochemical analyses.
      RESULTS: Cx32 was detected at cell-cell (intercellular) contact points in normal
      cells and exhibited punctate intercellular and intracytoplasmic staining in
      cancer cells. The frequency of Cx32 loss of expression was significantly higher
      in human adenocarcinomas than in normal stomach. As tumor cells were less
      differentiated, Cx32 expression levels and intercellular and intracytoplasmic
      staining were also significantly lower. The Cx32 expression pattern in the mouse
      gastric cancer model was similar in several important respects to that of human.
      In mucous metaplasia of the mouse stomach, Cx32 was mainly expressed in the
      cytoplasm of epithelial cells. There was also an inverse correlation between Cx32
      expression and cell proliferation in mouse tumors. However, there was no
      difference in the levels of Cx32 mRNA between normal and cancerous tissues.
      CONCLUSIONS: These findings suggest that altered Cx32 expression, a loss of
      intercellular Cx32 and a gain of intracytoplasmic Cx32 in the form of punctate
      "dot", plays an important role in the formation of gastric adenocarcinomas.

PMID- 21082352
TI  - Pharmacological basis for the medicinal use of psyllium husk (Ispaghula) in
      constipation and diarrhea.
AB  - BACKGROUND: The objective of this study was to determine the pharmacological
      basis of the medicinal use of psyllium husk (Ispaghula) in gastrointestinal
      motility disorders. METHODS: In-vivo studies were conducted on mice, and isolated
      rabbit jejunum and guinea-pig ileum were used in in-vitro experiments. RESULTS:
      The crude extract of Ispaghula (Po.Cr) had a laxative effect in mice at 100 and
      300 mg/kg, which was partially sensitive to atropine or SB203186 (5-HT(4)
      antagonist). At higher doses (500 and 1,000 mg/kg), Po.Cr had antisecretory and
      antidiarrheal activity. In guinea-pig ileum, Po.Cr (1-10 mg/ml) had a stimulatory
      effect, which was partially sensitive to atropine or SB203186. In rabbit jejunum,
      Po.Cr had a partially atropine-sensitive stimulatory effect followed by
      relaxation at 10 mg/ml. The relaxation was inhibited by the presence of L-NAME, a
      nitric oxide (NO) synthase inhibitor, or methylene blue, a guanylyl cyclase
      inhibitor. Similarly, the relaxant effect of Po.Cr on K(+) (80 mM)-induced
      contractions, was attenuated in the presence of L-NAME or methylene blue.
      Activity-directed fractionation of Po.Cr revealed that the gut stimulatory and
      inhibitory constituents were widely distributed in the aqueous and organic
      fractions. CONCLUSION: This study demonstrates that Ispaghula has a gut
      stimulatory effect, mediated partially by muscarinic and 5-HT(4) receptor
      activation, which may complement the laxative effect of its fiber content, and a
      gut-inhibitory activity possibly mediated by blockade of Ca(2+) channels and
      activation of NO-cyclic guanosine monophosphate pathways. This may explain its
      medicinal use in diarrhea. It is, perhaps, also intended by nature to offset an
      excessive stimulant effect.

PMID- 21082353
TI  - Comparative evaluation of different doses of green tea extract alone and in
      combination with sulfasalazine in experimentally induced inflammatory bowel
      disease in rats.
AB  - BACKGROUND: The exact etiopathology of inflammatory bowel disease is still
      unclear. Most of the therapies present are directed towards symptomatic
      improvement. Surgical therapy in the form of restorative proctocolectomy is
      reserved for the terminal stage disease, which is unresponsive to medical
      therapy. The present study was conducted to evaluate the effect of green tea in
      experimentally induced inflammatory bowel disease. METHODS: A total of 36 animals
      were included in the study. The animals were divided into five groups (n = 6):
      Group I-Vehicle (ethanol), group II-TNBS + ethanol, group III-green tea-treated
      group was divided into two sub-groups on the basis of different doses: group IIIA
      TNBS + green tea (35 mg/kg), group IIIB-TNBS + green tea (70 mg/kg), group IV
      TNBS + sulfasalazine (360 mg/kg), group V-TNBS + sulfasalazine (360 mg/kg) +
      green tea (least effective dose found in group III). After completion of 2 weeks
      of treatment, the rats were killed under ether anesthesia by cervical dislocation
      for assessment of intestinal inflammation, histological analysis, myeloperoxidase
      assay, malondialdehyde assay, and TNF-alpha estimation. RESULTS: The study showed
      that green tea alone and in combination with sulfasalazine reduced inflammatory
      changes induced by tri nitro benzene sulfonic acid in rats. This reduction is
      associated with reduced malondialdehyde, lipid peroxidation, and TNF-alpha. This
      correlates well with both gross morphological and histopathological scores.
      CONCLUSIONS: The authors concluded that a combination of green tea extract with
      sulfasalazine showed greater efficacy than single drug treatment.

PMID- 21082354
TI  - Insulin-like growth factor 1 mediates 5-fluorouracil chemoresistance in
      esophageal carcinoma cells through increasing survivin stability.
AB  - Insulin-like growth factor 1 (IGF-1) inhibits 5-fluorouracil (5-Fu)-induced
      apoptosis in esophageal carcinoma cells; however, the mechanisms for IGF-1
      induced 5-Fu chemoresistance remain unknown. In the human esophageal carcinoma
      cell line, CE48T/VGH, we show that IGF-1 up-regulated survivin expression at the
      post-transcriptional level and this up-regulation is mediated by both the PI3
      K/Akt and casein kinase 2 signaling pathways. We then examine whether IGF-1
      induced 5-Fu chemoresistance is mediated through up-regulation of survivin.
      Ectopic expression of survivin inhibits 5-Fu-induced apoptosis; furthermore, the
      abolition of survivin expression sensitizes cells to 5-Fu treatment and prevents
      the anti-apoptotic function of IGF-1 in esophageal carcinoma cell lines. We also
      found that ectopic expression of survivin or treatment with IGF-1 inhibits the
      release of Smac/DIABLO and caspases activation after 5-Fu treatment. Our results
      strongly suggest that IGF-1 inhibits 5-Fu induced apoptosis through increasing
      survivin levels, which prevents Smac/DIABLO release and blocks the activation of
      caspases. Therefore, up-regulation of IGF-1 and survivin would seem to be
      responsible for 5-Fu chemoresistance in esophageal cancer patients and these
      factors may be the valuable predictors of 5-Fu chemoresistance in esophageal
      carcinoma.

PMID- 21082355
TI  - Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death
      via, mitochondrial mediated caspase-dependent mechanism.
AB  - Okadaic acid (OA) is a specific and potent protein phosphatase inhibitor and
      tumor promoter. The present study establishes the role of reactive oxygen species
      (ROS) and mitogen activated protein kinases in cell death induced by okadaic
      acid. The study showed that okadaic acid is cytotoxic at 10 nM with an IC50 of
      100 nM in U-937 cells. The CVDE assay and mitochondrial dehydrogenase assay
      showed a time dependent cytotoxicity. The phase contrast visualization of the OA
      treated cells showed the apoptotic morphology and was confirmed with esterase
      staining for plasma membrane integrity. OA activated caspases-7, 9 and 3, PARP
      cleavage and induced nuclear damage in a time and dose dependent manner.
      Compromised mitochondrial membrane potential, release of cytochrome-c and
      apoptosis inducing factor confirms the involvement of mitochondria. A time
      dependent decrease in glutathione levels and a dose dependent increase in ROS
      with maximum at 30 min were observed. ROS scavenger-N-acetyl cysteine,
      mitochondrial stabilizer-cyclosporin-A, and broad spectrum caspase inhibitor Z
      VAD-FMK inhibited the OA induced caspase-3 activation, DNA damage and cell death
      but caspase-8 inhibitor had no effect. OA activated p38 MAPK and JNK in a time
      dependent manner, but not ERK1/2. MAP kinase inhibitors SB203580, SP600125 and
      PD98059 confirm the role of p38 MAPK and JNK in OA induced caspase-3 activation
      and cell death. Over all, our results indicate that OA induces cell death by
      generation of ROS, and activation of p38 MAPK and JNK, and executed through
      mitochondrial mediated caspase pathway.

PMID- 21082356
TI  - In vivo imaging of early stage apoptosis by measuring real-time caspase-3/7
      activation.
AB  - In vivo imaging of apoptosis in a preclinical setting in anticancer drug
      development could provide remarkable advantages in terms of translational
      medicine. So far, several imaging technologies with different probes have been
      used to achieve this goal. Here we describe a bioluminescence imaging approach
      that uses a new formulation of Z-DEVD-aminoluciferin, a caspase 3/7 substrate, to
      monitor in vivo apoptosis in tumor cells engineered to express luciferase. Upon
      apoptosis induction, Z-DEVD-aminoluciferin is cleaved by caspase 3/7 releasing
      aminoluciferin that is now free to react with luciferase generating measurable
      light. Thus, the activation of caspase 3/7 can be measured by quantifying the
      bioluminescent signal. Using this approach, we have been able to monitor caspase
      3 activation and subsequent apoptosis induction after camptothecin and
      temozolomide treatment on xenograft mouse models of colon cancer and
      glioblastoma, respectively. Treated mice showed more than 2-fold induction of Z
      DEVD-aminoluciferin luminescent signal when compared to the untreated group.
      Combining D: -luciferin that measures the total tumor burden, with Z-DEVD
      aminoluciferin that assesses apoptosis induction via caspase activation, we
      confirmed that it is possible to follow non-invasively tumor growth inhibition
      and induction of apoptosis after treatment in the same animal over time.
      Moreover, here we have proved that following early apoptosis induction by caspase
      3 activation is a good biomarker that accurately predicts tumor growth inhibition
      by anti-cancer drugs in engineered colon cancer and glioblastoma cell lines and
      in their respective mouse xenograft models.

PMID- 21082357
TI  - European health systems and the internal market: reshaping ideology?
AB  - Departing from theories of distributive justice and their relation with the
      distribution of health care within society, especially egalitarianism and
      libertarianism, this paper aims at demonstrating that the approach taken by the
      European Court of Justice regarding the application of the Internal Market
      principles (or the market freedoms) to the field of health care services has
      introduced new values which are more concerned with a libertarian view of health
      care. Moreover, the paper also addresses the question of how these new values
      introduced by the Court may affect common principles of European health systems,
      such as equity and accessibility.

PMID- 21082358
TI  - Clinicopathological assessment of locally recurrent rectal cancer and relation to
      local re-recurrence.
AB  - BACKGROUND: Local re-recurrence after R0 resection of local recurrence of rectal
      cancer (LRRC) is not rare. The purpose of this study was to examine the
      pathological features of LRRC and determine the prognostic factors. METHODS:
      Twenty-one patients underwent R0 resection of LRRC without preoperative therapy
      from 2000 to 2008. Tumor progression patterns were classified into three types:
      A, expanding type; B, infiltrating type; and C, intermediate type. Distant
      isolated cancer cells (DICCs) were defined as cancer cells present in isolation
      and at a distance (>1 mm) from the tumor edge. RESULTS: Venous invasion was
      identified in all but one patient (95%). DICCs were observed in 11 of 21 cases.
      Type A patients had a significantly lower local re-recurrence rate (0/5) compared
      with type B and/or C patients (11/16, P = 0.012) and a significantly lower
      incidence of distant metastasis compared with type B and C patients (0/5 vs.
      13/16, respectively; P = 0.0028). Multivariate regression analysis identified
      venous invasion of the primary lesion (P = 0.027) and tumor progression patterns
      (P = 0.039) as independent predictors of local re-recurrence. CONCLUSIONS: The
      main features of LRRC were infiltrating growth, venous invasion, and DICCs. Tumor
      progression patterns correlated with local re-recurrence and distant metastasis.
      Preoperative adjuvant therapy to terminate peri-tumor cancer cells may be
      required for better tumor control.

PMID- 21082359
TI  - The potentials and challenges of an academic-community partnership in a low-trust
      urban context.

PMID- 21082360
TI  - The absolute configurations of hydroxy fatty acids from the royal jelly of
      honeybees (Apis mellifera).
AB  - 9-Hydroxy-2E-decenoic acid (9-HDA) is a precursor of the queen-produced
      substance, 9-oxo-2E-decenoic acid (9-ODA), which has various important functions
      and roles for caste maintenance in honeybee colonies (Apis mellifera). 9-HDA in
      royal jelly is considered to be a metabolite of 9-ODA produced by worker bees,
      and it is fed back to the queen who then transforms it into 9-ODA. Recently we
      found that 9-HDA is present in royal jelly as a mixture of optical isomers (R:S,
      2:1). The finding leads us to suspect that chiral fatty acids in royal jelly are
      precursors of semiochemicals. Rather than looking for semiochemicals in the
      mandibular glands of the queen bee, this study involves the search for precursors
      of pheromones from large quantities of royal jelly. Seven chiral hydroxy fatty
      acids, 9,10-dihydroxy-2E-decenoic, 4,10-dihydroxy-2E-decenoic, 4,9-dihydroxy-2E
      decenoic, 3-hydroxydecanoic, 3,9-dihydroxydecanoic, 3,11-dihydroxydodecanoic, and
      3,10-dihydroxydecanoic acids were isolated. The absolute configurations of these
      acids were determined using the modified Mosher's method, and it was revealed
      that, similar to 9-HDA, five acids are present in royal jelly as mixtures of
      optical isomers.

PMID- 21082362
TI  - Newer methods for microbiologic diagnosis of pediatric infections.
AB  - There are several advantages in making a specific diagnosis of an infectious
      disease. In addition to better patient care with appropriate therapy, once the
      diagnosis is established considerable financial expense is spared and preventive
      measures can be initiated. The microbiology laboratory is vital in the isolation
      and identification of organisms. It is also possible by finding an antigen,
      metabolic product or nucleic acid unique to that specific organism that a
      diagnosis can be made and susceptibility testing can also be performed.

PMID- 21082361
TI  - Mutations in the survival motor neuron (SMN) protein alter the dynamic nature of
      nuclear bodies.
AB  - The childhood disorder spinal muscular atrophy (SMA) is caused by reduced
      expression of the survival motor neuron (SMN) protein. SMN is a multifunctional
      protein that has been implicated in the production, processing and transport of
      RNA and ribonucleoproteins (RNPs). Within the nucleus, SMN is predominantly
      targeted to Cajal bodies (CB), which are involved in the maturation and
      processing of several subclasses of RNPs. Here, we show that the SMN exon 2b
      encoded domain (SMN2b) is independently sufficient to mediate CB targeting, but
      that the resulting bodies are less dynamic than those containing full-length SMN
      protein. We also show that while two SMN proteins harbouring SMA-causing point
      mutations (A2G and S262I) are efficiently targeted to CBs, they also display
      reduced nuclear movement.

PMID- 21082363
TI  - A comparison of two implant systems in restoration of hip geometry in
      arthroplasty.
AB  - BACKGROUND: Restoration of hip offset and leg length during THA is often limited
      by available implant geometries. The recent introduction of femoral components
      with a modular junction at the base of the neck (two modular junction components)
      has expanded the options to restore femoral offset and leg length.
      QUESTIONS/PURPOSES: We asked (1) whether a femoral component with two modular
      junctions would predict by templating more frequent restoration of preoperative
      offset and leg length abnormalities than one with single modular junctions; and
      (2) how our use of these options compared with national sales data. PATIENTS AND
      METHODS: We retrospectively reviewed the preoperative templating data in 100
      primary THAs using single modular junction implants with only a neutral version
      stem and 100 THAs using two modular junction implants. We compared the frequency
      with which the desired leg length and offset were completely restored by
      preoperative templating in the two groups. RESULTS: Offset and leg lengths were
      restored to within 1 mm in 85% of cases with two modular junction implants and
      60% of cases with single modular junction implants. An anteverted or a
      retroverted neck was used in 25% of cases with the two modular junction stems.
      The national sales data revealed femoral neck components with version were used
      in 28% of cases. CONCLUSIONS: The use of a femoral component with two modular
      junctions resulted in more frequent ability to restore femoral offset and leg
      length than a single modular junction. The advantage of clinical flexibility
      should be tempered by the potential concerns of prosthetic mechanical failure
      (which has been reported in another implant system with two modular junctions),
      increased third-body wear and corrosive debris, and increased prosthetic cost.
      LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21082364
TI  - Wear damage in mobile-bearing TKA is as severe as that in fixed-bearing TKA.
AB  - BACKGROUND: Mobile-bearing TKAs reportedly have no clinical superiority over
      fixed-bearing TKAs, but a potential benefit is improved polyethylene wear
      behavior. QUESTIONS/PURPOSES: We asked whether extent of damage and wear patterns
      would be less severe on retrieved mobile-bearing TKAs than on fixed-bearing TKAs
      and if correlations with patient demographics could explain differences in extent
      or locations of damage. METHODS: We performed damage grading and mapping of 48
      mobile-bearing TKAs retrieved due to osteolysis/loosening, infection, stiffness,
      instability or malpositioning. Visual grading used stereomicroscopy to identify
      damage, and a grade was assigned based on extent and severity. Each damage mode
      was then mapped onto a photograph of the implant surface, and the area affected
      was calculated. RESULTS: Marked wear damage occurred on both surfaces, with
      burnishing, scratching, and pitting the dominant modes. Damage occurred over a
      large portion of both surfaces, exceeding the available articular borders in
      nearly 30% of implants. Wear of mobile-bearing surfaces included marked third
      body debris. Damage on tibiofemoral and mobile-bearing surfaces was not
      correlated with patient BMI or component alignment. Damage on mobile-bearing
      surfaces was positively correlated with length of implantation and was greater in
      implants removed for osteolysis or instability than in those removed for
      stiffness or infection. CONCLUSIONS: Each bearing surface in mobile-bearing
      implants was damaged to an extent similar to that in fixed-bearing implants,
      making the combined damage score higher than that for fixed-bearing implants.
      Mobile-bearing TKAs did not improve wear damage, providing another argument
      against the superiority of these implants over fixed-bearing implants.

PMID- 21082365
TI  - Morphology and properties of brain endothelial cells.
AB  - The molecular advances in various aspects of brain endothelial cell function in
      steady states are considerable and difficult to summarize in one chapter.
      Therefore, this chapter focuses on endothelial permeability mechanisms in steady
      states and disease namely vasogenic edema. The morphology and properties of
      caveolae and tight junctions that are involved in endothelial permeability to
      macromolecules are reviewed. Endothelial transport functions are briefly
      reviewed. Diseases with alterations of endothelial permeability are mentioned and
      details are provided of the molecular alterations in caveolae and tight junctions
      in vasogenic edema. Other factors involved in increased endothelial permeability
      such as the matrix metalloproteinases are briefly discussed. Of the modulators of
      endothelial permeability, angioneurins such as the vascular endothelial growth
      factors and angiopoietins are discussed. The chapter concludes with a brief
      discussion on delivery of therapeutic substances across endothelium.

PMID- 21082366
TI  - Morphology and properties of pericytes.
AB  - Pericytes were described in 1873 by the French scientist Charles-Marie Benjamin
      Rouget and were originally called Rouget cells. The Rouget cell was renamed some
      years later due to its anatomical location abluminal to the endothelial cell (EC)
      and luminal to parenchymal cells. In the brain, pericytes are located in
      precapillary arterioles, capillaries and postcapillary venules. They deposit
      elements of the basal lamina and are totally surrounded by this vascular
      component. Pericytes are important cellular constituents of the blood-brain
      barrier (BBB) and actively communicate with other cells of the neurovascular unit
      such as ECs, astrocytes, and neurons. Pericytes are local regulatory cells that
      are important for the maintenance of homeostasis and hemostasis, and are a source
      of adult pluripotent stem cells. Further understanding of the role played by this
      intriguing cell may lead to novel targeted therapies for neurovascular diseases.

PMID- 21082367
TI  - Morphology and properties of astrocytes.
AB  - Astrocytes were identified about 150 years ago, and, for the longest time, were
      considered to be supporting cells in the brain providing trophic, metabolic, and
      structural support for neural networks. Research in the last 2 decades has
      uncovered many novel molecules in astrocytes and the finding that astrocytes
      communicate with neurons via Ca2+ signaling, which leads to release of chemical
      transmitters, termed gliotransmitters, has led to renewed interest in their
      biology. This chapter will briefly review the unique morphology and molecular
      properties of astrocytes. The reader will be introduced to the role of astrocytes
      in blood-brain barrier (BBB) maintenance, in Ca2+ signaling, in synaptic
      transmission, in CNS synaptogenesis, and as neural progenitor cells. Mention is
      also made of the diseases in which astrocyte dysfunction has a role.

PMID- 21082368
TI  - The blood-cerebrospinal fluid barrier: structure and functional significance.
AB  - The choroid plexus (CP) of the blood-CSF barrier (BCSFB) displays fundamentally
      different properties than blood-brain barrier (BBB). With brisk blood flow (10 *
      brain) and highly permeable capillaries, the human CP provides the CNS with a
      high turnover rate of fluid (~400,000 MUL/day) containing micronutrients,
      peptides, and hormones for neuronal networks. Renal-like basement membranes in
      microvessel walls and underneath the epithelium filter large proteins such as
      ferritin and immunoglobulins. Type IV collagen (alpha3, alpha4, and alpha5) in
      the subepithelial basement membrane confers kidney-like permselectivity. As in
      the glomerulus, so also in CP, the basolateral membrane utrophin A and
      colocalized dystrophin impart structural stability, transmembrane signaling, and
      ion/water homeostasis. Extensive infoldings of the plasma-facing basal labyrinth
      together with lush microvilli at the CSF-facing membrane afford surface area, as
      great as that at BBB, for epithelial solute and water exchange. CSF formation
      occurs by basolateral carrier-mediated uptake of Na+, Cl-, and HCO3-, followed by
      apical release via ion channel conductance and osmotic flow of water through AQP1
      channels. Transcellular epithelial active transport and secretion are energized
      and channeled via a highly dense organelle network of mitochondria, endoplasmic
      reticulum, and Golgi; bleb formation occurs at the CSF surface. Claudin-2 in
      tight junctions helps to modulate the lower electrical resistance and greater
      permeability in CP than at BBB. Still, ratio analyses of influx coefficients
      (Kin) for radiolabeled solutes indicate that paracellular diffusion of small
      nonelectrolytes (e.g., urea and mannitol) through tight junctions is restricted;
      molecular sieving is proportional to solute size. Protein/peptide movement across
      BCSFB is greatly limited, occurring by paracellular leaks through incomplete
      tight junctions and low-capacity transcellular pinocytosis/exocytosis. Steady
      state concentration ratios, CSF/plasma, ranging from 0.003 for IgG to 0.80 for
      urea, provide insight on plasma solute penetrability, barrier permeability, and
      CSF sink action to clear substances from CNS.

PMID- 21082369
TI  - The blood-retinal barrier: structure and functional significance.
AB  - Formation and maintenance of the blood-retinal barrier is required for proper
      vision and loss of this barrier contributes to the pathology of a wide number of
      retinal diseases. The retina is responsible for converting visible light into the
      electrochemical signal interpreted by the brain as vision. Multiple cell types
      are required for this function, which are organized into eight distinct cell
      layers. These neural and glial cells gain metabolic support from a unique
      vascular structure that provides the necessary nutrients while minimizing
      interference with light sensing. In addition to the vascular contribution, the
      retina also possesses an epithelial barrier, the retinal pigment epithelium,
      which is located at the posterior of the eye and controls exchange of nutrients
      with the choroidal vessels. Together the vascular and epithelial components of
      the blood-retinal barrier maintain the specialized environment of the neural
      retina. Both the vascular endothelium and pigment epithelium possess a well
      developed junctional complex that includes both adherens and tight junctions
      conferring a high degree of control of solute and fluid permeability.
      Understanding induction and regulation of the blood-retinal barrier will allow
      the development of therapies aimed at restoring the barrier when compromised in
      disease or allowing the specific transport of therapies across this barrier when
      needed. This chapter will highlight the anatomical structure of the blood-retinal
      barrier and explore the molecular structure of the tight junctions that provide
      the unique barrier properties of the blood--retinal barrier.

PMID- 21082370
TI  - The blood-nerve barrier: structure and functional significance.
AB  - The blood-nerve barrier (BNB) defines the physiological space within which the
      axons, Schwann cells, and other associated cells of a peripheral nerve function.
      The BNB consists of the endoneurial microvessels within the nerve fascicle and
      the investing perineurium. The restricted permeability of these two barriers
      protects the endoneurial microenvironment from drastic concentration changes in
      the vascular and other extracellular spaces. It is postulated that endoneurial
      homeostatic mechanisms regulate the milieu interieur of peripheral axons and
      associated Schwann cells. These mechanisms are discussed in relation to nerve
      development, Wallerian degeneration and nerve regeneration, and lead neuropathy.
      Finally, the putative factors responsible for the cellular and molecular control
      of BNB permeability are discussed. Given the dynamic nature of the regulation of
      the permeability of the perineurium and endoneurial capillaries, it is suggested
      that the term blood-nerve interface (BNI) better reflects the functional
      significance of these structures in the maintenance of homeostasis within the
      endoneurial microenvironment.

PMID- 21082371
TI  - Detection of multiple proteins in intracerebral vessels by confocal microscopy.
AB  - Assessment of the blood-brain barrier (BBB) may involve the localization of
      endothelial proteins within the context of endothelial permeability to plasma
      proteins. The use of antibodies conjugated to fluorescent dyes, coupled with
      analysis by confocal microscopy, allows for the detection of multiple proteins in
      components of the neurovascular unit including endothelium and astrocytes. This
      chapter provides a detailed protocol for detection of three proteins in fixed or
      frozen sections of rat brain using three fluorophores with unique
      excitation/emission spectra. Also included is a protocol for tyramide signal
      amplification, which is useful for detecting proteins of low abundance, and
      methods for quantitation of intracerebral vessels expressing a particular protein
      of interest with and without BBB breakdown to plasma proteins.

PMID- 21082372
TI  - Multiparametric magnetic resonance imaging and repeated measurements of blood
      brain barrier permeability to contrast agents.
AB  - Breakdown of the blood-brain barrier (BBB) is present in several neurological
      disorders such as stroke, brain tumors, and multiple sclerosis. Noninvasive
      evaluation of BBB breakdown is important for monitoring disease progression and
      evaluating therapeutic efficacy in such disorders. One of the few techniques
      available for noninvasively and repeatedly localizing and quantifying BBB damage
      is magnetic resonance imaging (MRI). This usually involves the intravenous
      administration of a gadolinium-containing MR contrast agent (MRCA) such as
      Gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), followed by dynamic
      contrast-enhanced MR imaging (DCE-MRI) of brain and blood, and analysis of the
      resultant data to derive indices of blood-to-brain transfer. There are two
      advantages to this approach. First, measurements can be made repeatedly in the
      same animal; for instance, they can be made before drug treatment and then again
      after treatment to assess efficacy. Secondly, MRI studies can be multiparametric.
      That is, MRI can be used to assess not only a blood-to-brain transfer or influx
      rate constant (Ki or K1) by DCE-MRI but also complementary parameters such as:
      (1) cerebral blood flow (CBF), done in our hands by arterial spin-tagging (AST)
      methods; (2) magnetization transfer (MT) parameters, most notably T1sat, which
      appear to reflect brain water-protein interactions plus BBB and tissue
      dysfunction; (3) the apparent diffusion coefficient of water (ADCw) and/or
      diffusion tensor, which is a function of the size and tortuosity of the
      extracellular space; and (4) the transverse relaxation time by T2-weighted
      imaging, which demarcates areas of tissue abnormality in many cases. The accuracy
      and reliability of two of these multiparametric MRI measures, CBF by AST and DCE
      MRI determined influx of Gd-DTPA, have been established by nearly congruent
      quantitative autoradiographic (QAR) studies with appropriate radiotracers. In
      addition, some of their linkages to local pathology have been shown via
      corresponding light microscopy and fluorescence imaging. This chapter describes:
      (1) multiparametric MRI techniques with emphasis on DCE-MRI and AST-MRI; (2) the
      measurement of the blood-to-brain influx rate constant and CBF; and (3) the role
      of each in determining BBB permeability.

PMID- 21082373
TI  - Detection of brain pathology by magnetic resonance imaging of iron oxide micro
      particles.
AB  - Contrast agents are widely used with magnetic resonance imaging (MRI) to increase
      the contrast between regions of interest and the background signal, thus
      providing better quality information. Such agents can work in one of two ways,
      either to specifically enhance the signal that is produced or to localize in a
      specific cell type of tissue. Commonly used image contrast agents are typically
      based on gadolinium complexes or super-paramagnetic iron oxide, the latter of
      which is used for imaging lymph nodes. When blood-brain barrier (BBB) breakdown
      is a feature of central nervous system (CNS) pathology, intravenously
      administered contrast agent enters into the CNS and alters contrast on MR scans.
      However, BBB breakdown reflects downstream or end-stage pathology. The initial
      recruitment of leukocytes to sites of disease such as multiple sclerosis (MS),
      ischemic lesions, or tumours takes place across an intact, but activated, brain
      endothelium. Molecular imaging affords the ability to obtain a "non-invasive
      biopsy" to reveal the presence of brain pathology in the absence of significant
      structural changes. We have developed smart contrast agents that target and
      reversibly adhere to sites of disease and have been used to reveal activated
      brain endothelium when images obtained by conventional MRI look normal. Indeed,
      our selectively targeted micro-particles of iron oxide have revealed the early
      presence of cerebral malaria pathology and ongoing MS-like plaques in clinically
      relevant models of disease.

PMID- 21082374
TI  - Measuring the integrity of the human blood-brain barrier using magnetic resonance
      imaging.
AB  - The evaluation of blood-brain barrier (BBB) integrity with contrast-enhanced
      magnetic resonance imaging (MRI) may prove valuable in the setting of certain
      brain pathologies, such as brain tumors and acute ischemic stroke. Various MRI
      protocols have been developed to explore the integrity of the BBB by monitoring
      the leakage of intravenously administered contrast medium into the brain
      parenchyma. In its simplest form, BBB integrity is assessed qualitatively, by
      determining the presence or absence of contrast-enhancement on a structural MR
      image. When a dynamic contrast-enhanced (DCE) MRI protocol is combined with a
      suitable pharmacokinetic model, DCE-MRI can map the spatial distribution of BBB
      integrity throughout the brain and assist with evaluating the effects of therapy.
      Several model-free surrogate measures of BBB permeability have been recently
      proposed, all of which can be readily computed from standard dynamic
      susceptibility contrast MRI perfusion scans. Contrast-enhanced MRI offers
      multiple strategies for evaluating BBB integrity.

PMID- 21082375
TI  - Assessing blood-cerebrospinal fluid barrier permeability in the rat embryo.
AB  - The rat is a useful model for studies of embryonic blood-CSF function in that the
      embryos are large enough to collect sufficient fluid samples for analysis and
      exteriorized embryos can be kept viable for several hours in order to conduct
      longer term experiments. Both quantitative and qualitative methods that are
      similar to those used in adult studies can be used to assess blood-CSF function
      in the rat embryo; however, there are technical aspects of these studies that are
      more challenging. The choice of the methods to be used depends largely on the
      question being asked. This chapter describes in detail the precise steps that
      need to be taken to keep rat embryos in a good physiological state while
      conducting the experiments, how to administer markers into the embryonic
      circulation, and how to sample blood and/or CSF from embryos. How to evaluate the
      results obtained is outlined at the end of each method, together with notes on
      some limitations that are inherent in developmental studies.

PMID- 21082376
TI  - Detection of blood-nerve barrier permeability by magnetic resonance imaging.
AB  - The blood-nerve barrier (BNB) separates the endoneurium from the endovascular
      space and the epineurial connective tissue. An intact BNB is very important for
      integrity and functions of the nerve fibers within the endoneurial space.
      Disruption of the BNB which leads to functional and structural impairment of the
      peripheral nerve plays an important role in many disorders of the peripheral
      nerve like Wallerian degeneration, inflammatory nerve disorders, and
      demyelination. So far, this increased BNB permeability can only be assessed ex
      vivo. Assessing BNB disruption in vivo would be of great value for studying
      disorders of the peripheral nervous system. Gadofluorine M (Gf), a new
      amphiphilic contrast agent for MRI, accumulates in rat nerves with increased
      permeability of the BNB. After application of Gf, T1-weighted MR images show
      contrast enhancement of nerves with a disrupted BNB. This new tool of assessing
      BNB permeability in vivo is described.

PMID- 21082377
TI  - Isolation of human brain endothelial cells and characterization of lipid raft
      associated proteins by mass spectroscopy.
AB  - The blood-brain barrier (BBB) limits the movements of molecules, nutrients, and
      cells from the systemic blood circulation into the central nervous system (CNS),
      and vice versa, thus allowing an optimal microenvironment for CNS development and
      function. The brain endothelial cells (BECs) form the primary barrier between the
      blood and the CNS. In addition, pericytes, neurons, and astrocytes that make up
      the neurovascular unit support the BEC functions and are essential to maintain
      this restrictive permeability phenotype. To better understand the molecular
      mechanisms underlying BBB properties, we propose a method to study the proteome
      of detergent resistant microdomain, namely lipid rafts, from human primary
      cultures of BECs. This chapter describes a robust human BECs isolation protocol,
      standard tissue culture protocols, ECs purity assessment protocols, lipid raft
      microdomain isolation method, and a mass spectrometry analysis technique to
      characterize the protein content of membrane microdomains.

PMID- 21082378
TI  - Analysis of mouse brain microvascular endothelium using laser capture
      microdissection coupled with proteomics.
AB  - The blood-brain barrier (BBB) has been well studied in terms of its
      pharmacological properties. However, for a better understanding of the molecular
      mechanisms regulating these activities, means to thoroughly investigate the BBB
      at the genomic and proteomic levels are essential. Global gene expression
      analysis platforms have, in fact, provided a venue for cataloguing the BBB
      transcriptome. By comparison, and largely because of technical issues, there have
      been few comprehensive studies of the cerebral microvasculature at the protein
      level. Recent advances in both microdissection techniques and proteomic
      analytical tools have nonetheless circumvented many of these obstacles, allowing
      for isolation of relatively pure cell populations from complex tissues in situ
      and profiling of cellular proteomes. For example, immunohistochemistry-guided
      laser capture microdissection (immuno-LCM) provides the unique opportunity to
      selectively remove brain microvascular endothelial cells from the surrounding
      cell populations at the BBB, while supporting downstream proteomic analysis. In
      this chapter, we describe the use of immuno-LCM coupled with a sensitive, high
      resolution, hybrid linear ion trap coupled with Fourier transform mass
      spectrometry (FTMS) for proteomic profiling of mouse brain microvascular
      endothelium, a crucial cellular component of the BBB. We provide details of the
      quick double-immunostaining protocol for immuno-LCM, laser capture process,
      sample pooling, and protein recovery followed by in-gel digestion of protein
      sample, mass spectrometric analysis, and protein identification. Using such an
      approach to obtain comprehensive protein expression profiles of the cerebral
      endothelium in situ will enable detailed understanding of the crucial mediators
      of brain microvascular signaling and BBB function in both normal and
      pathophysiological conditions.

PMID- 21082379
TI  - Molecular and functional characterization of P-glycoprotein in vitro.
AB  - The blood-brain barrier (BBB) physically and metabolically functions as a
      neurovascular interface between the brain parenchyma and the systemic
      circulation, and regulates the permeability of several endogenous substrates and
      xenobiotics in and out of the central nervous system. Several membrane-associated
      transport proteins, such as P-glycoprotein (P-gp), multidrug resistance
      associated proteins, breast cancer resistance protein, and organic anion
      transporting polypeptides, have been characterized at the BBB and identified to
      play a major role in regulating the brain bioavailability of several
      pharmacological agents. This chapter reviews several well-established techniques
      for the study of the molecular expression, cellular localization, and functional
      activity of transport proteins in primary and immortalized cell culture systems
      of the BBB. In particular, we describe the molecular characterization of P
      gp/MDR1 at the transcript level using semiquantitative polymerase chain reaction
      (PCR), at the protein level using immunoblotting, and at the cellular level using
      immunofluorescence. In addition, the uptake/efflux and transepithelial flux
      studies, which characterize P-gp transport activity, are described.

PMID- 21082380
TI  - Methods to study glycoproteins at the blood-brain barrier using mass
      spectrometry.
AB  - Glycosylation is the most common posttranslational modification of proteins in
      mammalian cells and is limited mainly to membrane and secreted proteins.
      Glycoproteins play several key roles in the physiology and pathophysiology of the
      blood-brain barrier (BBB) and are attractive as diagnostic markers and
      therapeutic targets for many neurological diseases. However, large-scale
      glycoproteomic studies of the BBB have been lacking, largely due to the
      complexity of analyzing glycoproteins and a lack of available tools for this
      analysis. Recent development of the hydrazide capture method and significant
      advances in mass spectrometry (MS)-based proteomics over the last few years have
      enabled selective enrichment of glycoproteins from complex biological samples and
      their quantitative comparisons in multiple conditions. In this chapter, we
      describe methods for: (1) isolating membrane and secreted proteins from BEC and
      other cells of the neurovascular unit, (2) enriching glycoproteins using
      hydrazide capture, and (3) performing label-free quantitative proteomics to
      identify differential glycoprotein expression in various biological conditions.
      Hydrazide capture, when coupled with label-free quantitative proteomics, is a
      reproducible and sensitive method that allows for quantitative profiling of a
      large number of glycoproteins from biological samples for the purposes of
      differential expression measurements and biomarker discovery.

PMID- 21082381
TI  - Novel models for studying the blood-brain and blood-eye barriers in Drosophila.
AB  - In species as varied as humans and flies, humoral/central nervous system barrier
      structures are a major obstacle to the passive penetration of small molecules
      including endogenous compounds, environmental toxins, and drugs. In vivo
      measurement of blood-brain physiologic function in vertebrate animal models is
      difficult and current ex vivo models for more rapid experimentation using, for
      example, cultured brain endothelial cells, only partially reconstitute the
      anatomy and physiology of a fully intact blood-brain barrier (BBB). To address
      these problems, we and others continue to develop in vivo assays for studying the
      complex physiologic function of central nervous system (CNS) barriers using the
      fruit fly Drosophila melanogaster (Dm). These methods involve the introduction of
      small molecule reporters of BBB physiology into the fly humoral compartment by
      direct injection. Since these reporters must cross the Dm BBB in order to be
      visible in the eye, we can directly assess genetic or chemical modulators of BBB
      function by monitoring retinal fluorescence. This assay has the advantage of
      utilizing a physiologically intact BBB in a model organism that is economical and
      highly amenable to genetic manipulation. In combination with other approaches
      outlined here, such as brain dissection and behavioral assessment, one can
      produce a fuller picture of BBB biology and physiology. In this chapter, we
      provide detailed methods for examining BBB biology in the fly, including a Dm
      visual assay to screen for novel modulators of the BBB.

PMID- 21082382
TI  - Zebrafish model of the blood-brain barrier: morphological and permeability
      studies.
AB  - The blood-brain barrier (BBB) is a monolayer of endothelial cells that is
      regulated by the proximity of a unique basement membrane and a tightly controlled
      molecular interaction between specialized subsets of cells including pericytes,
      astrocytes, and neurons. Working together, these cells form a neurovascular unit
      (NVU) that is dedicated to the local regulation of vascular function in the brain
      and BBB integrity. Accordingly, the intrinsic complexity of the cell-matrix-cell
      interactions of the NVU has made analyzing gene function in cell culture, tissue
      explants, and even animal models difficult and the inability to study gene
      function in the BBB in vivo has been a critical hurdle to advancing BBB
      research.Zebrafish has emerged as a premier vertebrate organism to model and
      analyze complex cellular interactions in vivo and genetic mechanisms of embryonic
      development. To this end, we provide a technical overview of the procedures that
      can be used in Zebrafish to analyze BBB integrity with a focus on the
      cerebrovasculature of adult fish where the BBB is now defined. The techniques
      that are used to measure the functional integrity, the cell biology, and the
      ultrastructure of the BBB include permeability assays, fluorescent imaging of
      reporter genes, and electron microscopy, respectively. Each can be applied to the
      functional analysis of mutant fish in ways that characterize the molecular
      sequelae to pathological insults that compromise BBB integrity. Due to the highly
      conserved nature of both the genetics and cell biology of zebrafish when compared
      with higher vertebrates, drug discovery techniques can be used in zebrafish
      models to complement drug development studies in other model systems.

PMID- 21082383
TI  - Methods to assess pericyte-endothelial cell interactions in a coculture model.
AB  - The blood-brain barrier (BBB) comprises the microvascular endothelial cells,
      pericytes, and astrocytes, which are connected by the extracellular matrix (ECM).
      Current BBB models focus solely on the microvascular endothelial cells which
      constitute a physical barrier by formation of tight junctions (TJs), while the
      impact of pericytes on barrier regulation is poorly understood. We established a
      coculture model from primary porcine brain capillary endothelial cells (PBCECs)
      and pericytes (PBCPs) to approach the in vivo situation. This model allows the
      examination of pericyte impact on pharmacological, transport, migration, and
      metabolic activity of the BBB. In vivo the interaction between pericytes and
      endothelial cells is partly controlled by the ECM which is remodeled by matrix
      metalloproteinases (MMPs). Both endothelial cells and pericytes secrete MMPs
      which are important not only for ECM remodeling but also for TJ cleavage. In this
      chapter, current methods to study the interactions of these cell types by ECM
      signaling as well as MMP secretion are described.

PMID- 21082384
TI  - Isolation and properties of an in vitro human outer blood-retinal barrier model.
AB  - The outer blood-retinal barrier is composed of a monolayer of retinal pigment
      epithelium (RPE), Bruch's membrane, and the choriocapillaris, which is
      fenestrated. An in vitro model that includes all these layers within a 3-D
      architecture confers a clear advantage over traditional monolayer cultures. Cells
      here, whether endothelial or epithelial, reside in conditions resembling that in
      vivo and can participate in cell-cell and cell-matrix cross talk. This chapter
      describes how a human trilayer culture model was generated with RPE (ARPE-19)
      cells cultured on the epithelial surface of amniotic membrane and with human
      umbilical vein derived endothelial cells (HUVEC) on the interstitial surface.
      This model resembles the outer retinal barrier both in restricting transport of
      small molecules (<4 kDa), possession of occludin-rich tight junctions in the RPE
      and fenestrated endothelial cells. Techniques used to test the generated trilayer
      properties are also described and these include imaging of structure and
      molecular occupancy of tight and adherens junctions, estimation of the barrier
      efficiency of trilayer by measurement of fluorescein and fluorescein-conjugated
      tracers under flow, measurement of secreted vascular endothelial growth factor-A
      and ultrastructural studies, which allow analyses of the fine structure of the
      tight junctions in the RPE, and the endothelial fenestra.

PMID- 21082385
TI  - Isolation and properties of endothelial cells forming the blood-nerve barrier.
AB  - The blood-nerve barrier (BNB) is one of the functional barriers sheltering the
      nervous system from circulating blood. It is very important to understand the
      cellular properties of endothelial cells of endoneurial origin because these
      cells constitute the bulk of the BNB. This chapter describes a standard protocol
      for isolating the endothelial cells forming the BNB. In addition, methods for
      confirming some of the barrier properties of isolated endothelial cells are also
      described.

PMID- 21082386
TI  - Treatment of focal brain ischemia with viral vector-mediated gene transfer.
AB  - Promoting functional recovery after ischemic brain injury has emerged as a
      potential approach for the treatment of ischemic stroke. An ideal restorative
      approach to enhance long-term functional recovery is to promote postischemic
      angiogenesis and neurogenesis. This chapter describes a system using adeno
      associated viral (AAV) vector-mediated vascular endothelial growth factor (VEGF)
      gene transfer into the ischemic brain. The methods described here for
      construction, production, and purification of AAV vector expressing VEGF gene can
      also be applied to producing AAV vectors expressing other genes. This chapter
      also illustrates the methods to produce mouse middle cerebral artery occlusion
      (MCAO), injection of viral vector into the mouse brain, and standard assays for
      determining the success of brain ischemia and gene transfer.

PMID- 21082387
TI  - Blood-brain barrier disruption in the treatment of brain tumors.
AB  - Standard chemotherapy administered systemically has a limited efficacy in the
      treatment of brain tumors. One of the major obstacles in the treatment of brain
      neoplasias is the impediment to delivery across the intact blood-brain barrier
      (BBB). Many innovative approaches have been developed to circumvent this
      obstacle. One such strategy is BBB disruption (BBBD), which successfully
      increases the delivery of antineoplastic agents to the central nervous system
      (CNS). This chapter describes the application of the BBBD technique in rats.
      Different methods to evaluate and measure BBB permeability following hyperosmolar
      mannitol infusion including Evans blue staining, albumin immunohistochemistry,
      and dynamic magnetic resonance imaging are also described.

PMID- 21082388
TI  - Integrated platform for brain imaging and drug delivery across the blood-brain
      barrier.
AB  - The development of imaging and therapeutic agents against neuronal targets is
      hampered by the limited access of probes into the central nervous system across
      the blood-brain barrier (BBB). The evaluation of drug penetration into the brain
      in experimental models often requires complex procedures, including drug
      radiolabeling, as well as determinations in multiple animals for each condition
      or time point. Prospective in vivo imaging of drug biodistribution may provide an
      alternative to "classical" pharmacokinetics and biodistribution studies in that a
      contrast-enhanced imaging signal could serve as a surrogate for the amount of
      drug or biologic delivered to the organ of interest. For the brain-targeting
      applications, it is necessary to develop formulation strategies that enable a
      simultaneous drug and contrast agent delivery across the BBB. In this chapter, we
      describe methods for encapsulating drugs into liposome nanocarriers with surface
      display of both the imaging contrast agent for one or multiple imaging modalities
      and the single-domain antibody that undergoes receptor-mediated transcytosis
      across the BBB. Contrast-enhanced imaging signal detected in the brain after
      intravenous injection of such formulation(s) is proportional to the amount of
      drug delivered into the brain parenchyma. This method allows for a prospective,
      noninvasive estimation of drug delivery, accumulation, and elimination from the
      brain.

PMID- 21082390
TI  - Isolation and culture of rhesus adipose-derived stem cells.
AB  - Adipose tissue is as an abundant and accessible source of stem cells with
      multipotent properties suitable for tissue engineering and regenerative medical
      applications. Rhesus monkeys are physiologically and phylogenetically similar to
      humans, and they and their cells are valuable for biomedical research and
      evaluation of preclinical therapies. Here, we describe methods for the isolation,
      culture, and differentiation of rhesus adipose-derived stem cells (rASCs).

PMID- 21082389
TI  - Targeting the choroid plexus-CSF-brain nexus using peptides identified by phage
      display.
AB  - Drug delivery to the central nervous system requires the use of specific portals
      to enable drug entry into the brain and, as such, there is a growing need to
      identify processes that can enable drug transfer across both blood-brain and
      blood-cerebrospinal fluid barriers. Phage display is a powerful combinatorial
      technique that identifies specific peptides that can confer new activities to
      inactive particles. Identification of these peptides is directly dependent on the
      specific screening strategies used for their selection and retrieval. This
      chapter describes three selection strategies, which can be used to identify
      peptides that target the choroid plexus (CP) directly or for drug translocation
      across the CP and into cerebrospinal fluid.

PMID- 21082391
TI  - Isolation of human adipose-derived stem cells from lipoaspirates.
AB  - Adipose tissue is as an abundant and accessible source of stem cells with
      multipotent properties suitable for tissue engineering and regenerative medical
      applications. Here, we describe methods from our own laboratory and the
      literature for the isolation and expansion of adipose-derived stem cells (ASCs).
      We present a large-scale procedure suitable for processing >100-ml volumes of
      lipoaspirate tissue specimens by collagenase digestion and a related procedure
      suitable for processing adipose tissue aspirates without digestion.

PMID- 21082392
TI  - Isolation of murine adipose-derived stem cells.
AB  - Murine models of obesity or reduced adiposity are a valuable resource for
      understanding the role of adipocyte dysfunction in metabolic disorders. Primary
      adipocytes grown in culture and derived from murine adipose tissue are essential
      for studying the mechanisms underlying adipocyte development and function.
      Herein, we describe methods for the isolation, expansion, and long-term storage
      of murine adipose-derived stem cells along with a protocol for inducing
      adipogenesis in this cell population.

PMID- 21082393
TI  - In vitro adult rat adipose tissue-derived stromal cell isolation and
      differentiation.
AB  - Mesenchymal stromal cell research has advanced significantly over the last
      decade, especially in the area of adult adipose-derived stem cells (ASCs). There
      are significant species differences in ASC harvest, as well as in vitro doubling
      time and differentiation. Selection of appropriate animal models for preclinical
      evaluations is critical for optimization and validation of ASC therapeutic
      effects. As such, in vitro studies are necessary precursors to in vivo ASC
      applications. Additionally, to elucidate environmental, disease, or trauma
      effects on native stromal cell populations, characterization of cells from
      unexposed individuals is necessary. Rats are an established immunocompetent small
      animal model for a large number of human disorders and toxin exposures in the
      majority of organ systems. Isolation and expansion techniques for rat ASCs
      continue to change with advances in technology and ASC biology. The information
      presented in this chapter is a summary of rat ASC harvest, isolation,
      quantification, and in vitro expansion.

PMID- 21082394
TI  - In vitro adult canine adipose tissue-derived stromal cell growth characteristics.
AB  - Stromal cells are undifferentiated cells found in embryonic and adult tissues.
      Adult mesenchymal stromal cells (MSCs) possess the properties of self renewal,
      long-term viability, multipotentiality, and immune privilege, which make them
      attractive candidates for regenerative medicine applications. In order to develop
      targeted adult stromal cell therapies for diseased and injured tissues in animals
      and humans, it is essential to have large-animal models. The dog represents not
      only a patient population, but is also a valuable experimental model. The dog has
      contributed significantly to the understanding of various human diseases such as
      genetic and musculoskeletal disorders. In order to optimize the use of stromal
      cell therapy in the dog as a patient or disease model, a comprehensive
      characterization of the cells is required.

PMID- 21082395
TI  - Adipogenic differentiation of adult equine mesenchymal stromal cells.
AB  - Equine adipose tissue-derived mesenchymal stem cells (ASCs) have only recently
      been investigated for their adipogenic, chondrogenic, and osteogenic
      differentiation potential. This chapter will briefly outline the molecular
      mechanisms leading to adipogenesis and the methods of equine adipose tissue
      harvest, ASC isolation, and adipogenic differentiation. The reader is also
      directed to other reported methods of adipogenesis for ASCs and mesenchymal stem
      cells (MSCs) from other tissues.

PMID- 21082396
TI  - Isolation and culture of porcine adipose tissue-derived somatic stem cells.
AB  - Adipose tissue-derived stem cells (ASCs) have been described for a number of
      laboratory animals and humans. Improved culture conditions and cellular
      characteristics of ASCs have been identified. ASCs can self-renew and
      differentiate into multiple tissue lineages. Further characterization of ASCs in
      this manner could enhance the isolation and purification of a population of
      mesenchymal stem cells (MSCs) from easily obtainable adipose tissue. These stem
      cell populations from domestic animals, which make attractive models for
      transplantation studies, will be valuable for the evaluation of their efficacy in
      tissue regeneration applications in the future. These cells may also represent a
      population more easily reprogrammable during somatic cell nuclear transfer and
      thus expedite the development of transgenic animals for models and production of
      valuable pharmaceutical proteins.

PMID- 21082397
TI  - Automated isolation and processing of adipose-derived stem and regenerative
      cells.
AB  - The popularity of nonhematopoietic, adult tissue-derived stem and progenitor
      cells for use as a cellular research tool, and ultimately as a clinical
      therapeutic, has increased exponentially over the past decade. Almost all adult
      derived stem/progenitor cells (autologous and allogeneic), with one exception,
      require at least some ex vivo expansion or further manipulation prior to use to
      satisfy efficacy and safety requirements for preclinical or clinical use. The
      principal reason is the relatively low frequency of these therapeutically
      valuable cells within any given adult tissue, except for adipose tissue, which
      has been shown to have at least two log greater concentrations of these
      progenitor cells. Therefore, use of autologous adipose-derived cells as both a
      research tool and cell therapeutic is feasible and has been shown to be both safe
      and efficacious in preclinical and clinical models of injury and disease. The
      development and utilization of automated processes and instrumentation such as
      Cytori Therapeutics' Celution(r) System to reduce variability and increase
      quality of the recovered cells is requisite for clinical use and preferred by
      basic researchers. Here, use of an automated, closed processing platform for
      isolation and concentration of adipose-derived stem and regenerative cells is
      described, including a profile of the isolated cells immediately prior to use,
      and commonly used methods to quantify and qualitatively assess the recovered
      cells.

PMID- 21082398
TI  - Methods for the purification and characterization of human adipose-derived stem
      cells.
AB  - Peripheral adipose tissue contains a population of clonogenic precursor cells
      referred to as adipose-derived stem cells (ASC) that retain the capacity to
      differentiate into multiple cell types including osteoblasts, adipocytes,
      chondrocytes, myocytes, and neuronal cells following ex vivo expansion. Recent
      studies have demonstrated that ASC are most likely derived from a perivascular
      niche within highly vascularised fat tissue, analogous to different mesenchymal
      cell populations identified in other tissues throughout the body. The following
      chapter describes techniques to prospectively isolate clonogenic ASC from adult
      human adipose tissue using antibodies directed against perivascular markers and
      methods to immunophenotypically characterize their ex vivo expanded progeny.

PMID- 21082399
TI  - Characterization of human adipose-derived stem cells using flow cytometry.
AB  - One of the hallmark characteristics of human adipose-derived stem cells (hASCs)
      is their ability to differentiate into cells of mesenchymal lineages. It is also
      becoming apparent that ASCs can mediate a therapeutic benefit through cytokine,
      paracrine-driven mechanisms influencing apoptosis, angiogenesis, and potent anti
      inflammatory responses. Although there is still no clear consensus on the antigen
      expression pattern that will define hASCs, a protocol is also presented for the
      flow cytometric analysis utilizing a series of antibody panels. The analysis of
      these surface epitope patterns can aide in the isolation and characterization of
      hASCs. Moreover, using this standardized antibody panel, direct comparisons can
      be made between ASCs isolated from various tissue sources, which will benefit the
      field by providing uniformity to the comparison process.

PMID- 21082400
TI  - Evaluation of cellular and humoral immune responses to allogeneic adipose-derived
      stem/stromal cells.
AB  - Adipose-derived mesenchymal stem or stromal cells (ASCs) are poised for clinical
      use in an allogeneic setting. Although ASCs have been shown to be nonimmunogenic
      by several laboratories, it is advisable for the investigator to confirm this for
      ASCs used in their studies due to variations in ASC production and the animal
      models in which they are used. We describe here the use of the mixed lymphocyte
      reaction (MLR) assay to determine immunogenicity and suppression by ASCs in vitro
      as well as assessing T cell responses to allogeneic ASC transplantation in vivo.
      A flow cytometry assay to determine serum antibody titer to transplanted ASCs is
      also described.

PMID- 21082402
TI  - Gel-based and gel-free proteomic technologies.
AB  - Proteomics refers to the analysis of expression, localization, functions,
      posttranslational modifications, and interactions of proteins expressed by a
      genome at a specific condition and at a specific time. Mass spectrometry (MS)
      based proteomic methods have emerged as a key technology for unbiased systematic
      and high-throughput identification and quantification of complex protein
      mixtures. These methods have the potential to reveal unknown and novel changes in
      protein interactions and assemblies that regulate cellular and physiological
      processes. Both gel-based (one-dimensional [1D] gel electrophoresis, two
      dimensional [2D] polyacrylamide gel electrophoresis, 2D difference in-gel
      electrophoresis [DIGE]) and gel-free (liquid chromatography [LC], capillary
      electrophoresis) approaches have been developed and utilized in a variety of
      combinations to separate proteins prior to mass spectrometric analysis. Detailed
      protocols for global proteomic analysis from adipose-derived stem cells (ASCs)
      using two central strategies, 2D-DIGE-MS and 2D-LC-MS, are presented here.

PMID- 21082401
TI  - Adipose-derived stromal cells: cytokine expression and immune cell contaminants.
AB  - The present method describes an immunoselection/depletion approach to isolate the
      native human adipose tissue-derived progenitor cells that are free from
      endothelial cells and immune cells by the use of magnetic nanobeads and
      microbeads coupled to antibodies. Moreover, methods to isolate and to analyse the
      distinct cell populations that constitute the microenvironment of the human
      adipose tissue progenitor cells, i.e. mature adipocytes, endothelial cells, and
      macrophages, are mentioned.

PMID- 21082403
TI  - Adipogenic differentiation of adipose-derived stem cells.
AB  - The primary physiological function of adipose-derived stem cells (ASCs) is to
      differentiate into adipose tissue. It is now possible to isolate, expand, and
      cryopreserve ASC from adipose depots of many animal species. These ASC can be
      induced to undergo adipogenic differentiation in vitro by exposure to a cocktail
      of chemical agents or inductive growth factors. The current chapter describes
      methods to induce adipogenesis and to quantify this differentiation process in
      vitro.

PMID- 21082405
TI  - Neural differentiation of human adipose tissue-derived stem cells.
AB  - While adult stem cells can be induced to transdifferentiate into multiple
      lineages of cells or tissues, their plasticity and utility for human therapy
      remains controversial. In this chapter, we describe methods for the
      transdifferentiation of human adipose tissue-derived stem cells (ASCs) along
      neural lineages using in vitro and in vivo systems. The in vitro neural
      differentiation of ASCs has been reported by several groups using serum-free
      cytokine induction, butylated hydroxyanisole (BHA) chemical induction, and
      neurosphere formation in combination with the cytokines, such as brain-derived
      neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF). For in vivo
      neurogenic induction, ASCs are treated with BDNF and bFGF to form neurospheres in
      vitro and then delivered directly to the brain. In this chapter, several detailed
      protocols for the effective neurogenic induction of ASCs in vitro and in vivo are
      described. The protocols described herein can be applied to further molecular and
      mechanistic studies of neurogenic induction and differentiation of ASCs. In
      addition, these methods can be useful for differentiating ASCs for therapeutic
      intervention in central nervous system disorders.

PMID- 21082404
TI  - Three-dimensional culture systems to induce chondrogenesis of adipose-derived
      stem cells.
AB  - Stem cells can easily be harvested from adipose tissue in large numbers for use
      in tissue-engineering approaches for cartilage repair or regeneration. In this
      chapter, we describe in vitro tissue-engineering models that we have used in our
      laboratory for the chondrogenic induction of adipose-derived stem cells (ASC). In
      addition to the proper growth factor environment, chondrogenesis requires cells
      to be maintained in a rounded morphology in three-dimensional (3D) culture, and
      thus properties of the biomaterial scaffold also play a critical role in ASC
      differentiation. Histologic and immunohistologic methods for assessing
      chondrogenesis are also presented. In general, 10-12 weeks are required to assess
      ASC chondrogenesis in these model systems.

PMID- 21082406
TI  - Osteogenic differentiation strategies for adipose-derived mesenchymal stem cells.
AB  - Adipose stem cell preparations, either obtained as a freshly isolated so-called
      stromal vascular fraction (SVF) or as cells cultured to homogeneity and then
      referred to as adipose stem cells (ASCs), have found widespread use in a broad
      variety of studies on tissue engineering and regenerative medicine applications,
      including bone repair.For newcomers within the field, but also for established
      research laboratories having up to 10 years of expertise in this research area,
      it may be convenient to strive for, and use consensus protocols (1) for studying
      the osteogenic differentiation potential of ASC preparations in vitro, and (2)
      for osteogenic induction regimes for in vivo implementation. To assist in
      achieving this goal, this chapter describes various step-by-step osteogenic
      differentiation protocols for adipose-derived stem cell populations (SVF as well
      as ASCs) currently applied within our laboratory, with particular emphasis on
      protocols aimed at intra-operative use. The protocols describe the use of
      inducing compounds, including the bone morphogenetic proteins (BMPs), 1,25
      dihydroxyvitamin-D3, and polyamines, as well as methods and parameters for
      evaluating the level of differentiation achieved.We would appreciate receiving
      feedback on the protocols described; this will facilitate the development of
      consensus protocols, which in turn will allow better comparison of data sets
      generated by different research groups. This continuing standardization, which
      might be reported on at international meetings like those of IFATS (
      http://www.IFATS.org ), might be of benefit for the whole ASC research community.

PMID- 21082407
TI  - Generation of adipose stromal cell-derived hepatic cells.
AB  - The demand for primary human hepatocytes to test the toxicity of new drug
      candidates and to develop cell therapies for liver disease far exceed the number
      of hepatocytes that can be isolated from donated tissues. Less than 700 whole
      livers per year are available for research applications. The ability to utilize
      nonhepatic progenitor cells, such as adipose stromal cells (ASCs), to generate
      derivatives that mimic primary human hepatocytes would enable the scale-up
      production of cell products for bioartifical liver-assist devices, cell therapy,
      and drug discovery applications. ASC hepatogenesis is a rapidly evolving field
      with improved protocols continually being reported in the literature. In this
      chapter, current and effective protocols for the expansion, hepatic
      differentiation, and functional characterization of ASC-derived hepatic cells are
      outlined. Two major features distinguish optimized methodologies: (a) cytokine
      mediated "reprogramming" of mesenchymal ASCs to enable transdifferentiation into
      endodermal cell lineages, and (b) treatment with sequential media formulations
      containing factors/extracellular matrices that mimic the temporal expression
      profiles seen during fetal liver development. Criteria for success are
      acquisition of hepatic functional activities, such as albumin/urea production and
      p450 CYP activities, at levels that approach those observed in primary human
      hepatocyte controls.

PMID- 21082408
TI  - Adipose stem cell differentiation into smooth muscle cells.
AB  - The differentiation of adipose-derived stem cells (ASCs) into functional smooth
      muscle cells has received limited investigation. Various methodologies for both
      in vitro and in vivo differentiation is described. In vitro differentiation is
      obtained by either chemical or mechanical stimulation, and is determined by
      expression of smooth muscle cell markers. In vivo differentiation studies include
      animal models of cardiovascular disease and one study with urinary bladder
      reconstruction. The ease of obtaining an abundant number of ASCs render this cell
      population useful for potential vascular therapies that require autologous smooth
      muscle cells.

PMID- 21082409
TI  - Endothelial and cardiac regeneration from adipose tissues.
AB  - For a long time, adipose tissue was only considered for its crucial role in
      energy balance and associated diseases. The discovery of the presence of immature
      cells highlights a putative role for these tissues as reservoirs of therapeutic
      cells. Indeed, since fat pads can be sampled by liposuction under local
      anesthesia in adult patients, adipose tissue represents a promising source of
      regenerative cells, particularly in cardiovascular regeneration. Indeed among
      other potentials, we and others have demonstrated the great angiogenic properties
      of adipose-derived stromal cells (ASCs) and the existence of peculiar cells, at
      least in mice, that are able to spontaneously give rise to functional
      cardiomyocytes. This review deciphers the different steps necessary to isolate,
      characterize, and manipulate such striking cells.

PMID- 21082410
TI  - Epithelial differentiation of human adipose-derived stem cells.
AB  - The versatile differentiation potential of adipose-derived stem cells (ASC) into
      cells of mesodermal, entodermal, and ectodermal origin places these cells at the
      forefront of cell-based therapies and cell transplantation. Epithelial
      differentiation of ASC may either be initiated by direct cell-cell or cell-matrix
      contacts, by chemical factors like retinoic acid, or via secreted cellular
      factors like cytokines, interleukins, or growth factors included in conditioned
      media.This protocol describes methods to induce the in vitro differentiation of
      ASC from human adipose tissue into the epithelial lineage, and describes the
      methods used to verify this induced differentiation. We present two
      differentiation protocols based on either retinoic acid or conditioned medium of
      cultured epithelial cells.

PMID- 21082411
TI  - Screening for epigenetic target genes that enhance reprogramming using lentiviral
      delivered shRNA.
AB  - Small molecules will need to be identified and/or developed that target protein
      classes limiting reprogramming efficiency. A specific class of proteins includes
      epigenetic regulators that silence, or minimize expression, of pluripotency genes
      in differentiated cells. To better understand the role of specific epigenetic
      modulators in reprogramming, we have used shRNA delivered by lentivirus to assess
      the significance of individual epi-proteins in reprogramming pluripotent gene
      expression.

PMID- 21082412
TI  - Adipogenic differentiation of human adipose-derived stem cells on 3D silk
      scaffolds.
AB  - Current treatment modalities for soft tissue defects due to various pathologies
      and trauma include autologous grafting and the use of commercially available
      fillers. However, these treatment methods are associated with a number of
      limitations, such as donor site morbidity and volume loss over time. As such,
      improved therapeutic options are needed. Tissue engineering techniques offer
      novel solutions to these problems through development of bioactive tissue
      constructs that can regenerate adipose tissue with an appropriate structure and
      function. The recent advances in the derivation and characterization of hASCs
      have led to numerous studies of soft tissue reconstruction. In this chapter, we
      discuss methods in which our laboratory has used hASCs and silk scaffolds for
      adipose tissue engineering. The use of naturally occurring and clinically
      acceptable materials such as silk protein for tissue-engineering applications
      poses advantages with respect to biocompatibility and mechanical and biological
      properties.

PMID- 21082413
TI  - A first approach for the production of human adipose tissue-derived stromal cells
      for therapeutic use.
AB  - Adipose tissue-derived stromal cells (ASCs) are promising tools for the new
      therapeutic field of regenerative medicine. Many research teams are intent on
      producing these cells for therapeutic purposes. The cell production must follow
      strict rules for safety and for constant quality of the cell product to ensure a
      reliable effect in patients. These rules are grouped under the generic term Good
      Manufacturing Practices. In this chapter, we describe the general concepts of ASC
      production for therapeutic use, explaining new terms such as traceability and
      qualification. We also introduce general requirements for the installation,
      equipment, material, and staff for the cell production. Then, we outline a
      general strategy for building a cell culture process. Finally, as an example, we
      describe the use of CellStackTM chambers and specific tube sets that allow for
      producing cells beginning with the stromal vascular fraction under near-closed
      conditions.

PMID- 21082414
TI  - Viral transduction of adipose-derived stem cells.
AB  - Increasing numbers of regenerative approaches now involve use of adult stem
      cells, like the bone marrow MSC or the adipose-derived ASC. With their ease of in
      vitro manipulation and successful tissue integration in vivo, the ASC makes an
      attractive candidate for gene delivery in vivo using viral-based gene therapy
      strategies. As such, this chapter describes methods for the transduction of human
      ASCs with two popular types of recombinant viruses: adenovirus and lentivirus.

PMID- 21082415
TI  - Use of adipose-derived stem cells in high-throughput screening to identify
      modulators of lipogenesis.
AB  - Drug discovery efforts have an increasing focus on functional cell-based
      screening to identify compounds that modulate targets presented in a relevant
      format. Historically, immortalized cell lines have been used in primary and
      secondary screens due to their ease of manipulation, transformation, and
      propagation. However, more researchers are using primary cells that present their
      drug targets in their natural context. Human primary cell isolation and
      propagation procedures have become efficient enough to provide these cells in the
      necessary scale for early stage drug discovery. Adult human stem cells provide an
      opportunity for investigating multiple pathways of differentiation, development,
      regeneration, and toxicity using a single cell source and type. Adipose-derived
      stem cells (ASCs) are an attractive adult human primary stem cell for drug
      discovery due their abundance in adipose tissue, ease of isolation, and
      propagation in culture. They can be expanded in high numbers and retain their
      unique properties to differentiate into multiple lineages. In this chapter, we
      describe a protocol to identify modulators of human ASC lipogenesis following
      partial differentiation to adipocytes.

PMID- 21082416
TI  - Preservation protocols for human adipose tissue-derived adult stem cells.
AB  - The development of simple but effective storage protocols for adult stem cells
      will greatly enhance their use and utility in tissue-engineering applications.
      There are three primary storage techniques, freezing (cryopreservation), drying
      (anhydrobiosis), and freeze drying (lyophilization), each with its own advantages
      and disadvantages. Cryopreservation has shown the most promise but is a fairly
      complex process, necessitating the use of chemicals called cryoprotective agents
      (CPAs), freezing equipment, and obviously, storage in liquid nitrogen.
      Preservation by desiccation is an alternative that attempts to reproduce a
      naturally occurring preservative technique, namely, the phenomenon of
      anhydrobiosis and requires the use of high (and possibly, toxic) concentration of
      CPAs as well as disaccharides (sugars). Lyophilization works by first
      cryopreserving (freezing) the material and then desiccating (drying) it by the
      process of sublimation or the conversion of ice (solid) to water vapor (gas
      phase). The purpose of this chapter is to present a general overview of these
      storage techniques and the optimal protocols/results obtained in our laboratory
      for long-term storage of adult stem cells using freezing storage and drying
      storage.

PMID- 21082417
TI  - Soft tissue reconstruction.
AB  - The potential of adipose-derived stem cells (ASCs) in clinical applications of
      soft tissue regeneration is immense. This chapter discusses the isolation and
      characterization of human ASCs, expansion in vitro, and relevant in vivo models
      for adipose tissue engineering.

PMID- 21082418
TI  - Methods for analyzing microRNA expression and function during osteogenic
      differentiation of human adipose tissue-derived mesenchymal stem cells.
AB  - MicroRNAs (miRNA) are single-stranded RNA molecules of 21-23 nucleotides in
      length that regulate gene expression at the posttranscriptional level. They may
      play important roles during osteogenic differentiation of adipose tissue-derived
      mesenchymal stem cells (hASC). In this chapter, we focus on the methods and
      strategies for elucidating miRNA function during osteogenic differentiation. We
      describe a miRNA expression analysis protocol, and a lentiviral vector strategy
      for the ectopic expression of miRNA in hASC to determine the role of miRNA during
      osteogenic differentiation. We also describe miRNA inhibition to further
      determine the role of miRNA during osteogenic differentiation, and a luciferase
      assay to demonstrate direct binding between a specific miRNA and its putative
      target.

PMID- 21082419
TI  - The generation and the manipulation of human multipotent adipose-derived stem
      cells.
AB  - In this chapter, we describe a method to isolate and to expand multipotent
      adipose-derived stem (hMADS) cells from human adipose tissue. We also describe
      culture conditions to differentiate them into adipocytes at a high rate. This
      culture system provides a powerful means for studying the first steps of human
      adipose cell development and a route for investigating effects of drugs on the
      biology of adipocytes. Finally, we provide a protocol to investigate gene
      function during proliferation and differentiation of hMADS cells by means of
      siRNA-mediated gene silencing approaches or forced expression by transducing
      hMADS cells permissive to infection with murine retrovirus vectors.

PMID- 21082420
TI  - Cell sheet technology for tissue engineering: the self-assembly approach using
      adipose-derived stromal cells.
AB  - In the past years, adipose tissue has spurred a wide interest, not only as a
      source of adult multipotent stem cells but also as a highly eligible tissue for
      reconstructive surgery procedures. Tissue engineering is one field of
      regenerative medicine progressing at great strides in part due to its important
      use of adipose-derived stem/stromal cells (ASCs). The development of diversified
      technologies combining ASCs with various biomaterials has lead to the
      reconstruction of numerous types of tissue-engineered substitutes such as bone,
      cartilage, and adipose tissues from rodent, porcine, or human ASCs. We have
      recently achieved the reconstruction of connective and adipose tissues composed
      entirely of cultured human ASCs and their secreted endogenous extracellular
      matrix components by a methodology known as the self-assembly approach of tissue
      engineering. The latter is based on the stimulation of ASCs to secrete and
      assemble matrix components in culture, leading to the production of cell sheets
      that can be manipulated and further assembled into thicker multilayer tissues. In
      this chapter, protocols to generate both reconstructed connective and adipocyte
      containing tissues using the self-assembly approach are described in detail. The
      methods include amplification and cell banking of human ASCs, as well as culture
      protocols for the production of individual stromal and adipose sheets, which are
      the building blocks for the reconstruction of multilayered human connective and
      adipose tissues, respectively.

PMID- 21082421
TI  - Differentiation of adipose-derived stem cells for tendon repair.
AB  - The goal of primary tendon repair is to increase tensile strength at the time of
      mobilization. Tendon repair and regeneration using mesenchymal stem cells have
      been described in several studies; however, the use of adipose derived stem cells
      (ASCs) for tendon repair has only recently been considered. In order to establish
      a suitable experimental model for the primary tendon repair using ASCs, this
      chapter describes the detailed methods for: (1) isolating stem cells from adipose
      tissue, (2) generation of a primary tendon injury and repair model, (3)
      evaluating functional restoration by measuring tensile strength, and (4)
      investigating the mechanisms involved in ASC-mediated tendon healing by
      histological and immunohistochemical analyses. Topical administration of ASCs to
      the site of injury accelerates tendon repair, as exhibited by a significant
      increase in tensile strength, direct differentiation of ASCs toward tenocytes and
      endothelial cells, and increases in angiogenic growth factors. These findings
      suggest that ASCs may have a positive effect on primary tendon repair and may be
      useful for future cell-based therapy.

PMID- 21082422
TI  - Adipose-derived stem cells for skin regeneration.
AB  - Intractable skin ulcers resulting from diabetes, ischemia and collagen diseases
      represent significant problems with few solutions. Cell-based therapy may hold
      promise in overcoming such disorders. In order to establish a suitable
      experimental model for the treatment of such ulcers using stem cells, this
      chapter describes detailed methods for: (1) isolation of stem cells from adipose
      tissue, termed adipose-derived stem cells (ASCs), (2) preparing a hybrid-type
      artificial dermis that consists of a type I collagen sponge and ASCs, (3)
      preparing intractable ulcers using Mitomycin C, and (4) evaluating the effect of
      wound healing histologically. ASCs seeded onto a type I collagen sponge are
      applied to intractable ulcers induced by topical application of Mitomycin C.
      Histological evaluation after 1 and 2 weeks revealed an increase in capillary
      density and granulation thickness of the hybrid-type artificial dermis. These
      findings suggest that ASCs may have a positive effect on wound healing and may be
      a useful tool for future cell-based therapy.

PMID- 21082423
TI  - Adipose-derived stem cells for periodontal tissue regeneration.
AB  - Mesenchymal stem cells can effectively regenerate destroyed periodontal tissue.
      Because periodontal tissues are complex, mesenchymal stem cells that can
      differentiate into many tissue types would aid periodontal tissue regeneration.
      Indeed, periodontal tissue regeneration using mesenchymal stem cells derived from
      adipose tissue or bone marrow has been performed in experimental animal models,
      such as rat, canine, swine, and monkey. We have shown that rat periodontal tissue
      can be regenerated with adipose-derived stem cells. Adipose tissue contains a
      large number of stromal cells and is relatively easy to obtain in large
      quantities, and thus constitutes a very convenient stromal cell source. In this
      chapter, we introduce a rat periodontal tissue regeneration model using adipose
      derived stem cells.

PMID- 21082424
TI  - Protein bioinformatics databases and resources.
AB  - In the past decades, a variety of publicly available data repositories and
      resources have been developed to support protein related information management,
      data-driven hypothesis generation and biological knowledge discovery. However,
      there is also an increasing confusion for the researchers who are trying to
      quickly find the appropriate resources to help them solve their problems. In this
      chapter, we present a comprehensive review (with categorization and description)
      of major protein bioinformatics databases and resources that are relevant to
      comparative proteomics research. We conclude the chapter by discussing the
      challenges and opportunities for developing new protein bioinformatics databases.

PMID- 21082425
TI  - A guide to UniProt for protein scientists.
AB  - One of the essential requirements of the proteomics community is a high quality
      annotated nonredundant protein sequence database with stable identifiers and an
      archival service to enable protein identification and characterization. The scope
      of this chapter is to illustrate how Universal Protein Resource (UniProt) (The
      UniProt Consortium, Nucleic Acids Res. 38:D142-D148, 2010) can be best utilized
      for proteomics purposes with a particular focus on exploiting the knowledge
      captured in the UniProt databases, the services provided and the availability of
      complete proteomes.

PMID- 21082426
TI  - InterPro protein classification.
AB  - Improvements in nucleotide sequencing technology have resulted in an ever
      increasing number of nucleotide and protein sequences being deposited in
      databases. Unfortunately, the ability to manually classify and annotate these
      sequences cannot keep pace with their rapid generation, resulting in an increased
      bias toward unannotated sequence. Automatic annotation tools can help redress the
      balance. There are a number of different groups working to produce protein
      signatures that describe protein families, functional domains or conserved sites
      within related groups of proteins. Protein signature databases include CATH
      Gene3D, HAMAP, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY,
      and TIGRFAMs. Their approaches range from characterising small conserved motifs
      that can identify members of a family or subfamily, to the use of hidden Markov
      models that describe the conservation of residues over entire domains or whole
      proteins. To increase their value as protein classification tools, protein
      signatures from these 11 databases have been combined into one, powerful
      annotation tool: the InterPro database (http://www.ebi.ac.uk/interpro/) (Hunter
      et al., Nucleic Acids Res 37:D211-D215, 2009). InterPro is an open-source protein
      resource used for the automatic annotation of proteins, and is scalable to the
      analysis of entire new genomes through the use of a downloadable version of
      InterProScan, which can be incorporated into an existing local pipeline. InterPro
      provides structural information from PDB (Kouranov et al., Nucleic Acids Res
      34:D302-D305, 2006), its classification in CATH (Cuff et al., Nucleic Acids Res
      37:D310-D314, 2009) and SCOP (Andreeva et al., Nucleic Acids Res 36:D419-D425,
      2008), as well as homology models from ModBase (Pieper et al., Nucleic Acids Res
      37:D347-D354, 2009) and SwissModel (Kiefer et al., Nucleic Acids Res 37:D387
      D392, 2009), allowing a direct comparison of the protein signatures with the
      available structural information. This chapter reviews the signature methods
      found in the InterPro database, and provides an overview of the InterPro resource
      itself.

PMID- 21082427
TI  - Reactome knowledgebase of human biological pathways and processes.
AB  - The Reactome Knowledgebase is an online, manually curated resource that provides
      an integrated view of the molecular details of human biological processes that
      range from metabolism to DNA replication and repair to signaling cascades. Its
      data model allows these diverse processes to be represented in a consistent way
      to facilitate usage as online text and as a resource for data mining, modeling,
      and analysis of large-scale expression data sets over the full range of human
      biological processes.

PMID- 21082429
TI  - A tutorial on protein ontology resources for proteomic studies.
AB  - The protein ontology (PRO) is designed as a formal and well-principled open
      biomedical ontologies (OBO) foundry ontology for proteins. The components of PRO
      extend from the classification of proteins, on the basis of evolutionary
      relationships at the full-length level, to the representation of the multiple
      protein forms of a gene, such as those resulting from alternative splicing,
      cleavage and/or posttranslational modifications, and protein complexes. As an
      ontology, PRO differs from a database in that it provides description about the
      protein types and their relationships. In addition, the representation of
      specific protein types, such as a phosphorylated protein form, allows precise
      definition of objects in pathways, complexes, or in disease modeling. This is
      useful for proteomics studies where isoforms and modified forms must be
      differentiated, and for biological pathway/network representation where the
      cascade of events often depends on a specific protein modification. PRO is
      manually curated starting with content derived from scientific literature. Only
      annotation with experimental evidence is included, and is in the form of
      relationship to other ontologies. In this tutorial, you will learn how to use the
      PRO resources to gain information about proteins of interest, such as finding
      conserved isoforms (ortho-isoforms), and different modified forms and their
      attributes. In addition, it will provide some details on how you can contribute
      to the ontology via the rapid annotation interface RACE-PRO.

PMID- 21082428
TI  - eFIP: a tool for mining functional impact of phosphorylation from literature.
AB  - Technologies and experimental strategies have improved dramatically in the field
      of genomics and proteomics facilitating analysis of cellular and biochemical
      processes, as well as of proteins networks. Based on numerous such analyses,
      there has been a significant increase of publications in life sciences and
      biomedicine. In this respect, knowledge bases are struggling to cope with the
      literature volume and they may not be able to capture in detail certain aspects
      of proteins and genes. One important aspect of proteins is their phosphorylated
      states and their implication in protein function and protein interacting
      networks. For this reason, we developed eFIP, a web-based tool, which aids
      scientists to find quickly abstracts mentioning phosphorylation of a given
      protein (including site and kinase), coupled with mentions of interactions and
      functional aspects of the protein. eFIP combines information provided by
      applications such as eGRAB, RLIMS-P, eGIFT and AIIAGMT, to rank abstracts
      mentioning phosphorylation, and to display the results in a highlighted and
      tabular format for a quick inspection. In this chapter, we present a case study
      of results returned by eFIP for the protein BAD, which is a key regulator of
      apoptosis that is posttranslationally modified by phosphorylation.

PMID- 21082430
TI  - Structure-guided rule-based annotation of protein functional sites in UniProt
      knowledgebase.
AB  - The rapid growth of protein sequence databases has necessitated the development
      of methods to computationally derive annotation for uncharacterized entries. Most
      such methods focus on "global" annotation, such as molecular function or
      biological process. Methods to supply high-accuracy "local" annotation to
      functional sites based on structural information at the level of individual amino
      acids are relatively rare. In this chapter we will describe a method we have
      developed for annotation of functional residues within experimentally
      uncharacterized proteins that relies on position-specific site annotation rules
      (PIR Site Rules) derived from structural and experimental information. These PIR
      Site Rules are manually defined to allow for conditional propagation of
      annotation. Each rule specifies a tripartite set of conditions whereby candidates
      for annotation must pass a whole-protein classification test (that is, have end
      to-end match to a whole-protein-based HMM), match a site-specific profile HMM
      and, finally, match functionally and structurally characterized residues of a
      template. Positive matches trigger the appropriate annotation for active site
      residues, binding site residues, modified residues, or other functionally
      important amino acids. The strict criteria used in this process have rendered
      high-confidence annotation suitable for UniProtKB/Swiss-Prot features.

PMID- 21082431
TI  - Modeling mass spectrometry-based protein analysis.
AB  - The success of mass spectrometry based proteomics depends on efficient methods
      for data analysis. These methods require a detailed understanding of the
      information value of the data. Here, we describe how the information value can be
      elucidated by performing simulations using synthetic data.

PMID- 21082432
TI  - Protein identification from tandem mass spectra by database searching.
AB  - Protein identification from tandem mass spectra is one of the most versatile and
      widely used proteomics workflows, able to identify proteins, characterize post
      translational modifications, and provide semi-quantitative measurements of
      relative protein abundance. This manuscript describes the concepts,
      prerequisites, and methods required to analyze a tandem mass spectrometry dataset
      in order to identify its proteins, by using a tandem mass spectrometry search
      engine to search protein sequence databases. The discussion includes instructions
      for extraction, preparation, and formatting of spectral datafiles; selection of
      appropriate search parameter settings; and basic interpretation of the results.

PMID- 21082433
TI  - LC-MS data analysis for differential protein expression detection.
AB  - In proteomic studies, liquid chromatography coupled with mass spectrometry (LC
      MS) is a common platform to compare the abundance of various peptides that
      characterize particular proteins in biological samples. Each LC-MS run generates
      data consisting of thousands of peak intensities for peptides represented by
      retention time (RT) and mass-to-charge ratio (m/z) values. In label-free
      differential protein expression studies, multiple LC-MS runs are compared to
      identify differentially abundant peptides between distinct biological groups.
      This approach presents a computational challenge because of the following reasons
      (i) substantial variation in RT across multiple runs due to the LC instrument
      conditions and the variable complexity of peptide mixtures, (ii) variation in m/z
      values due to occasional drift in the calibration of the mass spectrometry
      instrument, and (iii) variation in peak intensities caused by various factors
      including noise and variability in sample handling and processing. In this
      chapter, we present computational methods for quantification and comparison of
      peptides by label-free LC-MS analysis. We discuss data preprocessing methods for
      alignment and normalization of LC-MS data. Also, we present multivariate
      statistical methods and pattern recognition methods for detection of differential
      protein expression from preprocessed LC-MS data.

PMID- 21082434
TI  - Protein identification by spectral networks analysis.
AB  - While advances in tandem mass spectrometry (MS/MS) steadily increase the rate of
      generation of MS/MS spectra, standard algorithmic approaches for peptide
      identification recently seemed to be reaching the limit on the amount of
      information that could be extracted from MS/MS spectra. However, a closer look
      reveals that a common limiting procedure is to analyze each spectrum in
      isolation, even though high throughput mass spectrometry regularly generates many
      spectra from related peptides. By capitalizing on this redundancy we show that,
      similarly to the alignment of protein sequences, unidentified MS/MS spectra can
      also be aligned for the identification of modified and unmodified variants of the
      same peptide. Moreover, this alignment procedure can be iterated for the accurate
      grouping of multiple modification variants of the same peptides. Furthermore, the
      combination of shotgun proteomics with the alignment of spectra from overlapping
      peptides led to the development of Shotgun Protein Sequencing - similarly to the
      assembly of DNA reads into whole genomic sequences, we show that assembly of
      MS/MS spectra enables the highest ever de novo sequencing accuracy, while
      recovering nearly complete protein sequences. We further show that shotgun
      protein sequencing has the potential to overcome the limitations of -current
      protein sequencing approaches and thus catalyze the otherwise impractical
      applications of proteomics methodologies in studies of unknown proteins.

PMID- 21082435
TI  - Software pipeline and data analysis for MS/MS proteomics: the trans-proteomic
      pipeline.
AB  - The LC-MS/MS shotgun proteomics workflow is widely used to identify and quantify
      sample peptides and proteins. The technique, however, presents a number of
      challenges for large-scale use, including the diverse raw data file formats
      output by mass spectrometers, the large false positive rate among peptide
      assignments to MS/MS spectra, and the loss of connectivity between identified
      peptides and the sample proteins that gave rise to them. Here we describe the
      Trans-Proteomic Pipeline, a freely available open source software suite that
      provides uniform analysis of LC-MS/MS data from raw data to quantified sample
      proteins. In a straightforward manner, users can extract MS/MS information from
      raw data of many instrument formats, submit them to search engines for peptide
      identification, validate the results to remove false hits, combine together
      results of multiple search engines, infer sample proteins that gave rise to the
      identified peptides, and perform quantitation at the peptide and protein levels.

PMID- 21082436
TI  - Analysis of high-throughput ELISA microarray data.
AB  - Our research group develops analytical methods and software for the high
      throughput analysis of quantitative enzyme-linked immunosorbent assay (ELISA)
      microarrays. ELISA microarrays differ from DNA microarrays in several fundamental
      aspects and most algorithms for analysis of DNA microarray data are not
      applicable to ELISA microarrays. In this review, we provide an overview of the
      steps involved in ELISA microarray data analysis and how the statistically sound
      algorithms we have developed provide an integrated software suite to address the
      needs of each data-processing step. The algorithms discussed are available in a
      set of open-source software tools (http://www.pnl.gov/statistics/ProMAT).

PMID- 21082437
TI  - Proteomics databases and repositories.
AB  - With the advent of more powerful and sensitive analytical techniques and
      instruments, the field of mass spectrometry based proteomics has seen a
      considerable increase in the amount of generated data. Correspondingly, the need
      to make these data publicly available in centralized online databases has also
      become more pressing. As a result, several such databases have been created, and
      steps are currently being taken to integrate these different systems under a
      single worldwide data-sharing umbrella. This chapter will discuss the importance
      of such databases and the necessary infrastructure that these databases require
      for efficient operation. Furthermore, the various kinds of information that
      proteomics databases can store will be described, along with the different types
      of databases that are available today. Finally, a selection of prominent
      repositories will be described in more detail, together with the international
      ProteomExchange consortium that is aimed at uniting all the different databases
      in a global data sharing collaboration.

PMID- 21082438
TI  - Preparing molecular interaction data for publication.
AB  - It is now becoming more usual for journals to request the submission of the data
      accompanying an article to an appropriate public repository. Such users may
      access the data in a format appropriate for display and reanalysis. It is
      commonly accepted that molecular interaction databases will hold all the large
      scale interaction datasets and enrich this with lower throughput data. Previously
      this small-scale interaction data has been archively curated from the literature
      but, increasingly, deposition of such information is also being seen as an
      integral part of the publication process. This chapter acts as a brief guide to
      preparing both large- and small-scale data for publication and gives a range of
      different submission options.

PMID- 21082439
TI  - Submitting proteomics data to PRIDE using PRIDE Converter.
AB  - With the continuously growing amount of proteomics data being produced, it has
      become increasingly important to make these data publicly available so that they
      can be audited, reanalyzed, and reused. More and more journals are also starting
      to request the deposition of MS data in publicly available repositories for
      submitted proteomics manuscripts. In this chapter we focus on one of the most
      commonly used proteomics data repositories, PRIDE (the PRoteomics IDEntifications
      database, http://www.ebi.ac.uk/pride), and demonstrate how a new graphical user
      interface tool called PRIDE Converter (http://pride-converter.googlecode.com)
      greatly simplifies the submission of data to PRIDE.

PMID- 21082440
TI  - Automated data integration and determination of posttranslational modifications
      with the protein inference engine.
AB  - This chapter describes using the Protein Inference Engine (PIE) to integrate
      various types of data--especially top down and bottom up mass spectrometer (MS)
      data--to describe a protein's posttranslational modifications (PTMs). PTMs
      include cleavage events such as the n-terminal loss of methionine and residue
      modifications like phosphorylation. Modifications are key elements in many
      biological processes, but are difficult to study as no single, general method
      adequately characterizes a protein's PTMs; manually integrating data from several
      MS experiments is usually required. The PIE is designed to automate this process
      using a guess and refine process similar to how an expert manually integrates
      data. The PIE repeatedly "imagines" a possible modification set, evaluates it
      using available data, and then tries to improve on it. After many rounds of
      refinement, the resulting modification set is proposed as a candidate answer.
      Multiple candidate answers are generated to obtain both best and near-best
      answers. Near-best answers are crucial in allowing for proteins with more than
      one supported modification pattern (isoforms) and obtaining robust results given
      incomplete and inconsistent data.The goal of this chapter is to walk the reader
      through installing and using the downloadable version of PIE, both in general and
      by means of a specific, detailed example. The example integrates several types of
      experimental and background (prior) data. It is not a "perfect-world" scenario,
      but has been designed to illustrate several real-world difficulties that may be
      encountered when trying to analyze imperfect data.

PMID- 21082441
TI  - An integrated top-down and bottom-up strategy for characterization of protein
      isoforms and modifications.
AB  - Bottom-up and top-down strategies are two commonly used methods for mass
      spectrometry (MS) based protein identification; each method has its own
      advantages and disadvantages. In this chapter, we describe an integrated top-down
      and bottom-up approach facilitated by concurrent liquid chromatography-mass
      spectrometry (LC-MS) analysis and fraction collection for comprehensive high
      throughput intact protein profiling. The approach employs a high resolution
      reversed phase (RP) LC separation coupled with LC eluent fraction collection and
      concurrent on-line MS with a high field (12 T) Fourier-transform ion cyclotron
      resonance (FTICR) mass spectrometer. Protein elusion profiles and tentative
      modified protein identification are made using detected intact protein mass in
      conjunction with bottom-up protein identifications from the enzymatic digestion
      and analysis of corresponding LC fractions. Specific proteins of biological
      interest are incorporated into a target ion list for subsequent off-line gas
      phase fragmentation that uses an aliquot of the original collected LC fraction,
      an aliquot of which was also used for bottom-up analysis.

PMID- 21082442
TI  - Phosphoproteome resource for systems biology research.
AB  - PhospoPep version 2.0 is a project to support systems biology signaling research
      by providing interactive interrogation of MS-derived phosphorylation data from
      four different organisms. Currently the database hosts phosphorylation data from
      the fly (Drosophila melanogaster), human (Homo sapiens), worm (Caenorhabditis
      elegans), and yeast (Saccharomyces cerevisiae). The following will give an
      overview of the content and usage of the PhosphoPep database.

PMID- 21082443
TI  - Protein-centric data integration for functional analysis of comparative
      proteomics data.
AB  - High-throughput proteomic, microarray, protein interaction and other experimental
      methods all generate long lists of proteins and/or genes that have been
      identified or have varied in accumulation under the experimental conditions
      studied. These lists can be difficult to sort through for Biologists to make
      sense of. Here we describe a next step in data analysis--a bottom-up approach at
      data integration--starting with protein sequence identifications, mapping them to
      a common representation of the protein and then bringing in a wide variety of
      structural, functional, genetic, and disease information related to proteins
      derived from annotated knowledge bases and then using this information to
      categorize the lists using Gene Ontology (GO) terms and mappings to biological
      pathway databases. We illustrate with examples how this can aid in identifying
      important processes from large complex lists.

PMID- 21082444
TI  - Integration of proteomic and metabolomic profiling as well as metabolic modeling
      for the functional analysis of metabolic networks.
AB  - The integrated analysis of different omics-level data sets is most naturally
      performed in the context of common process or pathway association. In this
      chapter, the two basic approaches for a metabolic pathway-centric integration of
      proteomics and metabolomics data are described: the knowledge-based approach
      relying on existing metabolic pathway information, and a data-driven approach
      that aims to deduce functional (pathway) associations directly from the data.
      Relevant algorithmic approaches for the generation of metabolic networks of model
      organisms, their functional analysis, database resources, visualization and
      analysis tools will be described. The use of proteomics data in the process of
      metabolic network reconstruction will be discussed.

PMID- 21082445
TI  - Time series proteome profiling.
AB  - This chapter provides a detailed description of a method used to study temporal
      changes in the endoplasmic reticulum (ER) proteome of fibroblast cells exposed to
      ER stress agents (tunicamycin and thapsigargin). Differential stable isotope
      labeling by amino acids in cell culture (SILAC) is used in combination with crude
      ER fractionation, SDS-PAGE and LC-MS/MS to define altered protein expression in
      tunicamycin or thapsigargin treated cells versus untreated cells. Treated and
      untreated cells are harvested at different time points, mixed at a 1:1 ratio and
      processed for ER fractionation. Samples containing labeled and unlabeled proteins
      are separated by SDS-PAGE, bands are digested with trypsin and the resulting
      peptides analyzed by LC-MS/MS. Proteins are identified using Bioworks software
      and the Swiss-Prot database, whereas ratios of protein expression between treated
      and untreated cells are quantified using ZoomQuant software. Data visualization
      is facilitated by GeneSpring software.

PMID- 21082446
TI  - Assessing posttraumatic cognitive processes: the Event Related Rumination
      Inventory.
AB  - Cognitive processes in the aftermath of experiencing a major life stressor play
      an important role in the impact of the event on the person. Intrusive thoughts
      about the event are likely to be associated with continued distress, while
      deliberate rumination, aimed at understanding and problem-solving, should be
      predictive of posttraumatic growth (PTG). The Event Related Rumination Inventory
      (ERRI), designed to measure these two styles of rumination, is described and
      validation information is provided. Using a college student sample screened for
      having experienced highly stressful life events, data were obtained (N=323) to
      conduct an exploratory factor analysis that supported the two factors of the
      ERRI. Separate confirmatory factor analyses (CFA) on two additional samples
      (Ns=186 and 400) supported a two-factor model. The two ERRI factors were
      validated by comparison with related variables and by assessing their
      contributions to predicting distress and PTG in two samples (Ns=198 and 202) that
      had been combined to conduct the second CFA. Data indicate the ERRI has solid
      psychometric properties, captures variance not measured by stable differences in
      cognitive styles, and the separate factors are related to posttraumatic distress
      and growth as predicted by existing models of PTG.

PMID- 21082447
TI  - The epigenetics of suicide: explaining the biological effects of early life
      environmental adversity.
AB  - A number of recent studies have shown epigenetic alterations associated with
      suicidal behavior. These epigenetic mechanisms, which alter gene expression via
      alternative mechanisms to the coding DNA sequence, result from environmental
      effects acting on the genome. Studies in rodents indicate that variation in the
      early environment will trigger these epigenetic modifications and recent human
      data suggest the same may be true in humans.The expression of a number of genes,
      which are involved in normal brain functions and that have been shown to be under
      epigenetic control, seem to be dysregulated in suicide. The present review
      briefly describes the main epigenetic mechanisms involved in the regulation of
      gene expression and discusses recent findings of epigenetic alterations in
      suicidal behavior.

PMID- 21082448
TI  - The role of parental bonding and early maladaptive schemas in the risk of
      suicidal behavior repetition.
AB  - The current study examined the role of perceived parental bonding and early
      maladaptive schemas in suicidal behavior. Participants completed measures of
      perceived parental bonding; schemas; risk of repeating suicidal behavior;
      anxiety; and depression following their presentation at Accident and Emergency
      with suicidal behavior. A suicidal behavior group (n = 60) differed from a
      comparison clinical (n = 46) and non-clinical (n = 48) group on measures of early
      maladaptive schemas, anxiety, and depression. No significant difference was noted
      between the suicidal behavior group and the comparison clinical group on a
      measure of parental bonding. Within the suicidal behavior group, significant
      associations were indicated between perceived parental bonding and risk of
      repetition of suicidal behavior; and early maladaptive schemas and risk of
      repetition of suicidal behavior. Early maladaptive schemas were found to mediate
      the relationship between perceived parental bonding and risk of repetition of
      suicidal behavior, with schemas of Social Alienation and Defectiveness/Shame
      offering mediator roles. The findings of the current study emphasize the
      complexities of suicidal behavior and factors that are associated with suicidal
      behavior. Although causality cannot be assumed, the findings highlight the
      importance and inter-relationships of not only perceived early experiences, but
      of underlying schemas in relation to suicidal behavior.

PMID- 21082449
TI  - The reinforcing properties of repeated deliberate self-harm.
AB  - The current study tested hypotheses derived from Joiner's (2005) interpersonal
      theory of suicide, which proposes that deliberate self-harm (DSH) becomes
      increasingly more reinforcing with repetition. One hundred six participants with
      a history of DSH completed questionnaires about their emotions and experience of
      physical pain during their most recent DSH episode. Consistent with prediction,
      people with more numerous past DSH episodes felt more soothed, more relieved, and
      calmer following their most recent episode of DSH. Contrary to prediction,
      greater numbers of past DSH episodes were associated with more intense physical
      pain during the most recent episode. The findings suggest that the emotion
      regulation functions of DSH may become more reinforcing with repetition.

PMID- 21082450
TI  - Pathways to high-lethality suicide attempts in individuals with borderline
      personality disorder.
AB  - The purpose of this study was to develop and test a model of high-lethality
      suicide attempts (HLSA) in individuals with Borderline Personality Disorder
      (BPD). An increased number of prior suicide attempts, substance use immediately
      prior to the attempt, and objective planning were proposed to lead directly to a
      HLSA, while aggression and impulsivity were hypothesized to lead indirectly to a
      HLSA through their associations with prior attempts. Path analysis revealed a
      revised model in which impulsivity was found to be significantly associated with
      both the lethality of the most recent attempt and the number of prior attempts.
      These results are discussed in terms of trait and crescendo models of suicidal
      behavior and their implications for suicide risk assessment among individuals
      with BPD.

PMID- 21082451
TI  - Depressive episodes with suicide attempts in severe depression: suicides and
      controls differ only in the later episodes of unipolar depression.
AB  - The aim of the present study was to investigate the distribution of suicide
      attempts across the depressive episodes in suicides and controls with a severe
      depression. A blind record evaluation was performed of 100 suicide victims and
      matched controls admitted to the Department of Psychiatry between 1956 and 1969
      and monitored to 2006. There was a similar number of episodes in suicides and
      controls and in the early episodes a similar number of suicide attempts in both
      groups. However, in the later episodes future suicides showed more suicide
      attempts as compared to controls. This was found for unipolar depression only.
      This difference was found despite previously shown similar rates of adequate
      treatment and improvement. In conclusion, more depressive episodes including
      suicide attempts appeared to be related to suicide.

PMID- 21082452
TI  - Suicide, big five personality factors, and depression at the American state
      level.
AB  - The research determined the relation of the 2004-2005 American state suicide
      rates to state means on neuroticism, agreeableness, extraversion, openness, and
      conscientiousness as assessed by Rentfrow, Gosling, and Potter (2008). Multiple
      regression strategies were used to analyze relations between state suicide rates
      and state personality means with state socioeconomic status, White population
      percent, urban population percent, and depression rates controlled. Multiple
      regression analysis showed that neuroticism accounted for 32.0% and agreeableness
      another 16.3% of the variance in suicide rates when demographics and depression
      were controlled. Lower neuroticism and lower agreeableness were associated with
      higher suicide rates. Lower neuroticism and lower agreeableness may be important
      risk factors for completed suicide but not suicidal ideation or attempted
      suicide.

PMID- 21082453
TI  - Brief report: why suicide? Perceptions of suicidal inpatients and reflections of
      clinical researchers.
AB  - Qualitatively oriented research (e.g., studies of suicide notes) has shed
      valuable light on the phenomenology of suicidal states. However, one draw back to
      this approach is that conclusions drawn from such data are inferential. In the
      current study, we took a more direct approach by having a sample of 52 suicidal
      inpatients provide written responses to the following query: Why suicide? A
      reliable coding system was developed that captured seven distinct response types
      to our prompt (i.e., suicide was seen as: the easy way out, a permanent solution,
      an escape from pain, the only option, self-oriented, related to hopelessness, and
      relationally-focused). In our discussion, we further reflect on these patient
      perceptions of suicide in terms of theory, research, and practice.

PMID- 21082456
TI  - Flow cell hydrodynamics and their effects on E. coli biofilm formation under
      different nutrient conditions and turbulent flow.
AB  - Biofilm formation is a major factor in the growth and spread of both desirable
      and undesirable bacteria as well as in fouling and corrosion. In order to
      simulate biofilm formation in industrial settings a flow cell system coupled to a
      recirculating tank was used to study the effect of a high (550 mg glucose l-1)
      and a low (150 mg glucose l-1) nutrient concentration on the relative growth of
      planktonic and attached biofilm cells of Escherichia coli JM109(DE3). Biofilms
      were obtained under turbulent flow (a Reynolds number of 6000) and the
      hydrodynamic conditions of the flow cell were simulated by using computational
      fluid dynamics. Under these conditions, the flow cell was subjected to wall shear
      stresses of 0.6 Pa and an average flow velocity of 0.4 m s-1 was reached. The
      system was validated by studying flow development on the flow cell and the
      applicability of chemostat model assumptions. Full development of the flow was
      assessed by analysis of velocity profiles and by monitoring the maximum and
      average wall shear stresses. The validity of the chemostat model assumptions was
      performed through residence time analysis and identification of biofilm forming
      areas. These latter results were obtained through wall shear stress analysis of
      the system and also by assessment of the free energy of interaction between E.
      coli and the surfaces. The results show that when the system was fed with a high
      nutrient concentration, planktonic cell growth was favored. Additionally, the
      results confirm that biofilms adapt their architecture in order to cope with the
      hydrodynamic conditions and nutrient availability. These results suggest that
      until a certain thickness was reached nutrient availability dictated biofilm
      architecture but when that critical thickness was exceeded mechanical resistance
      to shear stress (ie biofilm cohesion) became more important.

PMID- 21082455
TI  - Efficacy of surface-generated nitric oxide against Candida albicans adhesion and
      biofilm formation.
AB  - This report details the efficacy of nitric oxide (NO)-releasing xerogel surfaces
      composed of N-(6-aminohexyl)aminopropyl trimethoxysilane (AHAP3) and
      isobutyltrimethoxysilane (BTMOS) against Candida albicans adhesion, viability,
      and biofilm formation. A parallel plate flow cell assay was used to examine the
      effect of NO on planktonic fungal cells. Nitric oxide fluxes as low as 14 pmol
      cm(-2) s(-1) were sufficient to reduce fungal adhesion by ~49% over the controls
      after 90 min. By utilizing a fluorescence live/dead assay and replicate plating,
      NO flux was determined to reduce fungal viability in a dose-dependent manner. The
      formation of C. albicans biofilms on NO-releasing xerogel-coated silicon rubber
      (SiR) coupons was impeded when compared to control (non-NO-releasing) and bare
      SiR surfaces. The synergistic efficacy of NO and silver sulfadiazine against
      adhered fungal cells and biofilms is reported with increased killing and biofilm
      inhibition over NO alone.

PMID- 21082457
TI  - The influence of data shape acquisition process and geometric accuracy of the
      mandible for numerical simulation.
AB  - Computer-aided technologies have allowed new 3D modelling capabilities and
      engineering analyses based on experimental and numerical simulation. It has
      enormous potential for product development, such as biomedical instrumentation
      and implants. However, due to the complex shapes of anatomical structures, the
      accuracy of these technologies plays an important key role for adequate and
      accurate finite element analysis (FEA). The objective of this study was to
      determine the influence of the geometry variability between two digital models of
      a human model of the mandible. Two different shape acquisition techniques, CT
      scan and 3D laser scan, were assessed. A total of 130 points were controlled and
      the deviations between the measured points of the physical and 3D virtual models
      were assessed. The results of the FEA study showed a relative difference of 20%
      for the maximum displacement and 10% for the maximum strain between the two
      geometries.

PMID- 21082459
TI  - An approach to automatic blood vessel image registration of microcirculation for
      blood flow analysis on nude mice.
AB  - Image registration is often a required and a time-consuming step in blood flow
      analysis of large microscopic video sequences in vivo. In order to obtain stable
      images for blood flow analysis, frame-to-frame image matching as a preprocessing
      step is a solution to the problem of movement during image acquisition. In this
      paper, microscopic system analysis without fluorescent labelling is performed to
      provide precise and continuous quantitative data of blood flow rate in individual
      microvessels of nude mice. The performance properties of several matching metrics
      are evaluated through simulated image registrations. An automatic image
      registration programme based on Powell's optimisation search method with low
      calculation redundancy was implemented. The matching method by variance of ratio
      is computationally efficient and improves the registration robustness and
      accuracy in practical application of microcirculation registration. The presented
      registration method shows acceptable results in close requisition to analyse red
      blood cell velocities, confirming the scientific potential of the system in blood
      flow analysis.

PMID- 21082460
TI  - Influence of fluid-flow direction on effective permeability of the vertebral end
      plate: an analytical model.
AB  - Convective transports in the vertebral end plate (VEP) play a significant role in
      the homeostasis of the spine. A few studies hypothesised that the hydraulic
      resistance or effective permeability of the VEP could be dependant upon fluid
      flow direction. Results were influenced by species, region of interest within the
      end plate and pathology. Some results were contradictory. We propose an
      analytical model based on steady-state Newtonian flows in capillary media to
      develop a phenomenological analysis of convective transport through the VEP. This
      dependence was established using a biquadratic analytical function involving
      porosities of subchondral bone, capillary bed and cartilage end plate. Discussion
      of results provided a theoretical justification for variable and/or contradictory
      experimental results concerning the amount of energy lost by fluid during its
      course through the end plate. Tissue porosities and, especially, those relative
      to the capillary bed could strongly influence the dependence of fluid energy loss
      on flow direction and could potentially modify tissue homeostasis related to the
      day and night cycle.

PMID- 21082458
TI  - Sensitivity analysis of periprosthetic healing to cell migration, growth factor
      and post-operative gap using a mechanobiological model.
AB  - A theoretical rationale, which could help in the investigation of
      mechanobiological factors affecting periprosthetic tissue healing, is still an
      open problem. We used a parametric sensitivity analysis to extend a theoretical
      model based on reactive transport and computational cell biology. The numerical
      experimentation involved the drill hole, the haptotactic and chemotactic
      migrations, and the initial concentration of an anabolic growth factor. Output
      measure was the mineral fraction in tissue surrounding a polymethymethacrylate
      (PMMA) canine implant (stable loaded implant, non-critical gap). Increasing
      growth factor concentration increased structural matrix synthesis. A cell
      adhesion gradient resulted in heterogeneous bone distribution and a growth factor
      gradient resulted in homogeneous bone distribution in the gap. This could explain
      the radial variation of bone density from the implant surface to the drill hole,
      indicating less secure fixation. This study helps to understand the relative
      importance of various host and clinical factors influencing bone distribution and
      resulting implant fixation.

PMID- 21082461
TI  - Finite element studies of the mechanical behaviour of the diaphragm in normal and
      pathological cases.
AB  - The diaphragm is a muscular membrane separating the abdominal and thoracic
      cavities, and its motion is directly linked to respiration. In this study, using
      data from a 59-year-old female cadaver obtained from the Visible Human Project,
      the diaphragm is reconstructed and, from the corresponding solid object, a shell
      finite element mesh is generated and used in several analyses performed with the
      ABAQUS 6.7 software. These analyses consider the direction of the muscle fibres
      and the incompressibility of the tissue. The constitutive model for the isotropic
      strain energy as well as the passive and active strain energy stored in the
      fibres is adapted from Humphrey's model for cardiac muscles. Furthermore,
      numerical results for the diaphragmatic floor under pressure and active
      contraction in normal and pathological cases are presented.

PMID- 21082462
TI  - Accuracy of computer-aided geometric 3D reconstruction based on histological
      serial microgrinding preparation.
AB  - PURPOSE: For our research on computer-optimised and automated cochlear implant
      surgery, we pursue a model-based approach to overcome the limitations of
      currently available clinical imaging modalities. A serial cross section
      preparation procedure has been developed and evaluated concerning accuracy to
      serve for modelling of a digital anatomic atlas to make delicate soft tissue
      structures available for pre-operative planning. METHODS: A special grinding tool
      was developed allowing the setting of a specific amount of abrasion as
      equidistant slice thickness was considered a crucial step. Additionally, each
      actual abrasion was accurately measured and used during three-dimensional
      reconstruction of the serial cross-sectional images obtained via digital photo
      documentation after each microgrinding step. A well-known reference object was
      prepared using this procedure and evaluated in terms of accuracy. RESULTS:
      Reconstruction of the whole sample was achieved with an error less than 0.4%, and
      the edge lengths in the direction of abrasion could be reconstructed with an
      average error of 0.6 +/- 0.3 mm; both prove the realisation of equidistant
      abrasion. Using artificial registration fiducials and a custom-made algorithm for
      image alignment, parallelism and rectangularity could be preserved with average
      errors less than 0.4 degrees  +/- 0.3 degrees . CONCLUSION: We present a
      systematic, practicable and reliable method for the geometrically accurate
      reconstruction of anatomical structures, which is especially suitable for the
      middle and inner ear anatomy including soft tissue structures. For the first
      time, the quality of such a reconstruction process has been quantified and
      successfully proven for its usability.

PMID- 21082463
TI  - The couple as context: Latino gay male couples and HIV.
AB  - HIV-prevention efforts with gay men in relationships frequently omit primary
      partners. When they are considered, examinations of race/ethnicity are often
      overlooked despite higher infection rates among gay men of colour. Acknowledging
      both the need to contextualise the behaviours that may affect HIV risk for gay
      men of colour and the disproportionate impact of HIV on Latino gay men, the
      present study utilised semi-structured, qualitative interviews to explore
      relationship dynamics, sexual agreements and behaviours, safer sex choices and
      HIV risk among nine Latino gay male couples. All participants were HIV-negative
      and in concordant negative relationships. Additionally, nearly all reported
      closed agreements. Analysis revealed participants engaging in four behaviours
      that may actively reduce their HIV risk: approaching sexual agreements from a
      practical standpoint, maintaining a high literacy around HIV, having exposure to
      social support groups for Latino gay men and finding support in their
      relationship with another Latino gay man. Additional issues are raised where long
      term HIV prevention is concerned. Intimate relationships are an important context
      for understanding both HIV risk and prevention among Latino gay men. Likewise,
      race/ethnicity provides an indispensable perspective on all research with gay
      couples. Future prevention efforts with gay men must strive to include both.

PMID- 21082464
TI  - Pyrrolizidine alkaloids in honey: comparison of analytical methods.
AB  - Pyrrolizidine alkaloids (PAs) are a structurally diverse group of toxicologically
      relevant secondary plant metabolites. Currently, two analytical methods are used
      to determine PA content in honey. To achieve reasonably high sensitivity and
      selectivity, mass spectrometry detection is demanded. One method is an HPLC-ESI
      MS-MS approach, the other a sum parameter method utilising HRGC-EI-MS operated in
      the selected ion monitoring mode (SIM). To date, no fully validated or
      standardised method exists to measure the PA content in honey. To establish an LC
      MS method, several hundred standard pollen analysis results of raw honey were
      analysed. Possible PA plants were identified and typical commercially available
      marker PA-N-oxides (PANOs). Three distinct honey sets were analysed with both
      methods. Set A consisted of pure Echium honey (61-80% Echium pollen). Echium is
      an attractive bee plant. It is quite common in all temperate zones worldwide and
      is one of the major reasons for PA contamination in honey. Although only
      echimidine/echimidine-N-oxide were available as reference for the LC-MS target
      approach, the results for both analytical techniques matched very well (n = 8; PA
      content ranging from 311 to 520 ug kg(-1)). The second batch (B) consisted of a
      set of randomly picked raw honeys, mostly originating from Eupatorium spp. (0
      15%), another common PA plant, usually characterised by the occurrence of
      lycopsamine-type PA. Again, the results showed good consistency in terms of PA
      positive samples and quantification results (n = 8; ranging from 0 to 625 ug kg(
      1) retronecine equivalents). The last set (C) was obtained by consciously placing
      beehives in areas with a high abundance of Jacobaea vulgaris (ragwort) from the
      Veluwe region (the Netherlands). J. vulgaris increasingly invades countrysides in
      Central Europe, especially areas with reduced farming or sites with natural
      restorations. Honey from two seasons (2007 and 2008) was sampled. While only
      trace amounts of ragwort pollen were detected (0-6.3%), in some cases extremely
      high PA values were detected (n = 31; ranging from 0 to 13019 ug kg(-1), average
      = 1261 or 76 ug kg(-1) for GC-MS and LC-MS, respectively). Here the results
      showed significantly different quantification results. The GC-MS sum parameter
      showed in average higher values (on average differing by a factor 17). The main
      reason for the discrepancy is most likely the incomplete coverage of the J.
      vulgaris PA pattern. Major J. vulgaris PAs like jacobine-type PAs or
      erucifoline/acetylerucifoline were not available as reference compounds for the
      LC-MS target approach. Based on the direct comparison, both methods are
      considered from various perspectives and the respective individual strengths and
      weaknesses for each method are presented in detail.

PMID- 21082465
TI  - Validation of an enzyme-linked immunosorbent assay for qualitative screening of
      neomycin in muscle, liver, kidney, eggs and milk.
AB  - A rapid and sensitive enzyme-linked immunosorbent assay (ELISA) was used for the
      qualitative screening analysis of neomycin in food of animal origin (muscle,
      liver, kidney, eggs and milk) at levels corresponding to the European Union
      maximum residue limit (MRL) set for this substance. The method validation was
      performed according to the criteria of Commission Decision 2002/657/EC
      established for qualitative screening methods. In this regard, the following
      parameters were determined: detection capability (CCbeta), specificity, detection
      limit (LOD), quantification limit (LOQ), recovery, precision, linearity and
      ruggedness. LODs ranged from 5.7 microg kg(-1) in kidney to 29.3 microg kg(-1) in
      milk; LOQs ranged from 11.4 microg kg(-1) in kidney to 59.7 microkg(-1) in eggs.
      The recoveries from spiked samples at the MRL, half the MRL and double the MRL
      levels ranged from 65.8% to 122.8%, with a coefficient of variation (CV) between
      5.9% and 28.6%. The CCbeta value was less than the MRL for all examined matrices.
      Moderate variations of some critical factors in the sample pretreatment for
      muscle, milk and eggs were deliberately introduced for ruggedness evaluation and
      had a slight but not statistically significant effect on method performance. The
      proposed method is suitable for qualitative screening analysis of neomycin in the
      above-mentioned food in conformity with current European Union performance
      requirements.

PMID- 21082467
TI  - Evidence-based clinical practice: the effectiveness of music-based intervention
      for women experiencing forgiveness/grief issues.
AB  - This study evaluates the effectiveness of individual grief counselling using
      music-based intervention for women who had unresolved forgiveness/grief issues
      due to the loss of a loved one. Each individual (N = 21) completed the 12 bi
      weekly grief counselling sessions, in which the pretest and posttest data were
      collected. The results suggest that music-based intervention made a positive
      impact on the individuals who had current unresolved forgiveness/grief issues and
      depression symptoms. A strong positive correlation was observed between their
      perception of unresolved forgiveness/grief issues and their depression levels.
      Implications for evidence-based social work practice are discussed.

PMID- 21082468
TI  - A content analysis of intervention research in social work doctoral
      dissertations.
AB  - It is imperative for the social work profession that the on-going schism between
      researchers and practitioners commented on in the literature for the past 40
      years be effectively addressed. Doctoral programs are in a unique position to
      affect the production of research focusing on intervention. The purpose of this
      study was to determine if social work doctoral programs are currently successful
      in encouraging their doctoral candidates to engage in intervention research. A
      content analysis was conducted on 252 dissertation abstracts produced by social
      work doctoral students in 2006. Only 13.49% of the abstracts indicated a focus on
      social work intervention. The researchers argue that this finding indicates a
      need for a paradigm shift in social work education and practice.

PMID- 21082469
TI  - The value and purpose of the traditional qualitative literature review.
AB  - Both meta-analysis and traditional literature or narrative reviews strive to
      compile a great deal of information in an accessible and succinct manner. In
      recent years, social work researchers have been turning toward meta-analysis to
      identify issues in large areas of research. In order for meta-analysis to be a
      rigorous and objective source of information there are a certain set of
      assumptions that must be met about how to carry out the process of including and
      excluding various studies. However, when these assumptions are not met, the
      information provided can be misleading. Traditional literature reviews continue
      to offer a valid and important way to identify existing patterns and gaps in
      social work research. In fact, because they draw not only on quantitative (as
      does meta-analysis) but also qualitative studies their reach may often be
      broader. This paper examines the strengths, weaknesses and utility of both
      practices in social work research today.

PMID- 21082470
TI  - The missing link: the role of social work schools and evidence-based practice.
AB  - The translation and adoption of evidence-based practice principles has proved to
      be more difficult than researchers anticipated. Schools of social work are in a
      unique position to support this process within their home communities. Using the
      evidence-based practice process steps outlined by previous researchers, this
      article identifies specific strategies that schools of social work can adopt to
      support their broader communities as they attempt to adopt and sustain
      empirically supported interventions.

PMID- 21082471
TI  - Ideological schisms about HIV/AIDS helping systems in the African American
      community, with an emphasis on women.
AB  - This article is an initial exploration about the impact of ideological beliefs on
      helping services in the African American community. Newly infected HIV/AIDS cases
      place African Americans at 45% of such new cases, with African American women
      becoming infected at a rate 18 times that of Whites. Yet, helping services that
      are organic to African American women should be stronger through a discussion of
      cultural beliefs held in the community, where the genesis of helping services
      exists. Values and beliefs should be at the center of community partnerships,
      public media strategies, generalist-practice curricula in macro-level systems,
      and creating more space for relationship dialogue between African American men
      and women, which includes gender and racial distortions. Given the exponentially
      high numbers of HIV/AIDS cases in the African American community, a more earnest
      examination of values and beliefs is warranted.

PMID- 21082472
TI  - Parental perceptions of the Children In Need Of Treatment dental program.
AB  - This paper discusses the collaborative partnership involving the Middlesex-London
      Public Health Research, Education and Development site, the Ontario Ministry of
      Health Promotion and Sport, then Chronic Disease Prevention and Health Promotion
      Branch, and an academic institution in the first-ever research of parental
      perceptions of the Children In Need Of Treatment. This paper provides an overview
      of the Children In Need Of Treatment program, reviews the results of the research
      (a mailed, self-administered survey with a systematic random sample of parents
      from three health units whose children received dental treatment that was paid by
      Children In Need Of Treatment in 2006), and its subsequent recommendations. How
      these recommendations affected program planning and policy are examined. In
      conclusion, parents were very satisfied with the treating dentist and the
      Children In Need Of Treatment program, and found Children In Need Of Treatment to
      be vital in addressing the health of their children by attending to their urgent
      dental needs.

PMID- 21082473
TI  - Ecological risk and resilience perspective: a theoretical framework supporting
      evidence-based practice in schools.
AB  - Multidisciplinary school practitioners are clearly being called to use evidence
      based practices from reputable sources such as their own professional
      organizations and federal agencies. In spite of this encouragement, most schools
      are not regularly employing empirically supported interventions. This paper
      further promotes the use of this approach by describing the theoretical support
      for evidence-based practice in schools. The ecological risk and resilience
      theoretical framework presented fills a gap in the literature and advocates for
      evidence-based practice in schools by illustrating how it can assist
      practitioners such as school social workers to better address problems associated
      with school failure.

PMID- 21082474
TI  - Dissemination and implementation of evidence-based practice in the social
      services: a UK survey.
AB  - A cross sectional UK-wide survey assessed current levels of dissemination and
      implementation of evidence-based practice in social care and social work
      agencies. A structured questionnaire was e-mailed to 357 agencies of which 155
      (43.4%) completed and returned it. Although the results show that evidence-based
      practice in this area is still in its early stages, most respondents reported a
      good knowledge of evidence-based practice as well as the view that professional
      decisions should be informed by-but not only-research evidence. The lack of time,
      resources, information, and training are identified as the main barriers to be
      overcome for an effective implementation of evidence-based practice in the social
      services.

PMID- 21082475
TI  - Are curriculum decisions based on the evidence? How social work faculty members
      make choices in curriculum decisions.
AB  - An important step in translating evidence-based practice and empirically
      supported interventions into large-scale service improvements is to develop an
      understanding of practitioners' education and training in these practices. This
      understanding begins with discovering the factors that influence the decision
      making process by social work faculty regarding curriculum content for master's
      level social work programs. This exploratory study uses quantitative and
      qualitative survey data to examine the decision-making process used by 42
      master's level social work programs to select the models of direct practice
      taught in their master's level social work programs, and whether evidence-based
      practice and research evidence influences those decisions. We investigate faculty
      perceptions of curriculum effectiveness and discuss implications of our findings
      for social work educators making content and organization decisions regarding
      master's level social work curriculum.

PMID- 21082476
TI  - Evaluating the effectiveness of infant mental health enhanced case management for
      dependency populations.
AB  - Children who are receiving services for abuse and neglect are likely to have
      reduced developmental levels and are less prepared for success in school as a
      result. The progress of 144 children receiving services from The Children's Home
      Society of Florida was tracked with half being randomly assigned to a control
      group and half to an experimental group receiving enhanced infant mental health
      oriented case management services from two social work professionals in each of
      two locations in Tallahassee and West Palm Beach Florida. Those receiving
      enhanced case management showed significantly higher results in the following
      areas: more visits with their parents (for those removed from the family home),
      more service referrals, more completed assessments for services, more services
      based on the assessments they received, and more success in completing goals of
      treatment for which they were referred. Their parents had more contact with
      professionals to whom they were referred and had more success in completing goals
      of the treatment for which they were referred. Children who received intensive
      case management also showed improvement in their developmental skills related to
      problem solving from inception to completion of services. Implications for
      further research are considered.

PMID- 21082477
TI  - Factors associated with the use of evidence-based practices to treat
      psychological trauma by psychotherapists with trauma treatment expertise.
AB  - This paper investigates 10 socio-demographic and case characteristic variables as
      predictors of use of evidence-based practice and non-evidence-based practice in
      the treatment of psychological trauma. A national random sample of 2,400 trauma
      treatment specialists in all 50 states and the District of Columbia were sent
      surveys with a response rate of 29.6% (N = 711) usable surveys returned. Stepwise
      regressions conducted on evidence-based practice use indicated that special
      trauma training, older age, and higher percentage of PTSD on the case load were
      the only significant predictors of evidence-based practice use. Implications for
      trauma practices are indicated.

PMID- 21082478
TI  - In search of secret museums.

PMID- 21082479
TI  - Effects of handedness (left vs right) and cannabis abuse on intermanual
      coordination and negative symptoms in schizophrenic patients of the paranoid
      type.
AB  - Intermanual coordination as an index of interhemispheric transfer and negative
      symptoms were investigated in 50 left- and 42 right-handed schizophrenic
      inpatients of the paranoid type, also including drug abusers. The primary
      objective was to show that there were higher values in intermanual coordination
      and fewer manifestations of negative symptoms in the left-handed compared to the
      right-handed patients. This assumption was based on previous studies. Most
      importantly, right- and left-handed patients showed a different behaviour in
      intermanual coordination, when the duration of illness was taken into
      consideration. Thus, long-term left-handed paranoid patients performed better in
      intermanual coordination and showed fewer manifestations of negative symptoms
      than did long-term right-handed patients. These results were true for the large
      group of all patients, and among them for the subgroup of patients without drug
      abuse. Consequently, higher scores in intermanual coordination in left-handed
      patients may be related to a better interhemispheric crosstalk resulting in less
      pronounced negative symptoms. Secondary objectives assessed by explorative data
      analysis included the effects of cannabis abuse. While cannabis abuse may be more
      prevalent in left-handed patients, its effects may be more pronounced in right
      handed patients, scoring higher in intermanual coordination and lower in
      manifestations of negative symptoms.

PMID- 21082480
TI  - The baggage of health travelers.

PMID- 21082481
TI  - Patients without borders: understanding medical travel.
AB  - The rapidly growing medical travel industry has implications for the health
      systems of both sending and receiving countries. This article outlines the
      political economy of the industry and the potential opportunities and
      disadvantages it poses for access, equity, and the right to health. Although the
      trade carries economic benefits for countries receiving foreign medical patients,
      it comes at a cost to the provision of public health, through distortions in the
      health workforce and the development of two-tiered health systems. Inequalities
      and failures in the health systems of sending countries largely drive the need to
      travel for care.

PMID- 21082482
TI  - Traveling for medical care in a global world.
AB  - The international medical travel of Yemenis provides insight on terminology and
      models to use for the growing global phenomenon. Terminology for medical
      travelers ranges from "medical tourists" to "medical exiles." Differing models
      prioritize the global arena in which transnational medical travel occurs as (1) a
      global medical marketplace, (2) a global medical commons, (3) interlinked nation
      states, and (4) national or global citizens. Medical anthropology has a specific
      role in uncovering the lived experiences of patients who travel to often
      unfamiliar destinations to pursue care believed capable of alleviating suffering.

PMID- 21082483
TI  - "Cycling overseas": care, commodification, and stratification in cross-border
      reproductive travel.
AB  - Cross-border reproductive travel involves the movement of patients to undertake
      assisted reproductive treatment through technologies, such as in vitro
      fertilization and associated procedures otherwise denied to them due to cost,
      access, or regulatory restrictions. Based on fieldwork in Thailand, the United
      States, and the Czech Republic, we explore the commodification of reproductive
      bodies within this trade and the reduction of the nurturing affective labor of
      reproduction to exchange value. Second, we examine the intensification and
      globalization of the stratification of reproduction. These inequalities are
      illustrated though discussion of the trade in poor women's bodies for surrogacy
      and ova donation. Even reproductive body parts, ova, sperm, and embryos are
      stratified-marketed according to place of origin, the characteristics of their
      donors, and gender.

PMID- 21082484
TI  - Biotech pilgrims and the transnational quest for stem cell cures.
AB  - Thousands of patients with incurable neurodegenerative conditions from more than
      60 countries have sought fetal cell transplants in China since 2001. Drawing on
      24 months of ethnographic fieldwork, I investigate these transnational encounters
      occurring in the realm of experimental medicine. Critiquing popular notions of
      "medical tourism," I develop the alternative concept of "biotech pilgrimage" to
      reveal how faith intertwines with technology, travel, and the political economies
      of health care and medical research in a global era. Insights from pilgrimage
      theory enable us to question assumptions of leisure embedded in claims of tourism
      while also exploring new biopolitical practices that extend beyond the borders of
      the nation-state. I also demonstrate how materialist visions of salvation
      underlie medical practice and contribute to China's rising influence as a global
      technological leader.

PMID- 21082485
TI  - Plastic paradise: transforming bodies and selves in Costa Rica's cosmetic surgery
      tourism industry.
AB  - Long popular as a nature tourism destination, Costa Rica has recently emerged as
      a haven for middle class North Americans seeking inexpensive, state-of-the-art
      cosmetic surgery. This paper examines "cosmetic surgery tourism" in Costa Rica as
      a form of medicalized leisure, situated in elite private spaces and yet
      inextricably linked to a beleaguered national medical program. Through historical
      context and ethnographic analysis of activities at medical hotels and clinics, I
      describe how the recovery industry operates on the embodied subjectivities of
      visiting patients and their local caretakers. Recovery sociality and healing
      landscapes facilitate patients' transition through a period of post-surgical
      liminality and provide nostalgic transport to an imagined medical arcadia, while
      clinicians are attracted by a neoliberal promise of prosperity and autonomy.
      Ultimately, Costa Rica's transformation into a paradise of medical consumption
      and self-optimization is contingent on a mythology that obscures growing
      uncertainties and inequities in the nation's broader medical landscape.

PMID- 21082486
TI  - Feminine transformations: gender reassignment surgical tourism in Thailand.
AB  - Every year, hundreds of transgendered people from the United States, Europe,
      Asia, Canada, and Australia travel to Thailand to undergo cosmetic and gender
      reassignment surgeries (GRS). Many GRS clinics market themselves almost
      exclusively to non-Thai trans women (people assigned a male sex at birth who
      later identify as female). This article draws on ethnographic research with
      patients visiting Thailand for GRS to explore how trans women patients related
      their experience of medical care in Thailand to Thai cultural traditions, in
      particular "traditional" Thai femininity and Theravada Buddhist rituals and
      beliefs. Foreign patients in Thai hospital settings engage not only with medical
      practices but also with their perceptions of Thai cultural traditions--which
      inflect their feminine identifications. I draw on two patients' accounts of
      creating personal rituals to mark their gender reassignment surgery, placing
      these accounts within the context of biomedical globalization and debates about
      the touristic appropriation of non-"Western" cultural practices.

PMID- 21082487
TI  - Neuron-specific enolase and S 100B protein as predictors of outcome in ischaemic
      stroke.
AB  - BACKGROUND AND PURPOSE: As neuron-specific enolase (NSE) and S 100B protein are
      brain origin proteins, the aim of this study was to assess whether a single NSE
      and S 100B measure may predict clinical outcome of patients with cerebral
      ischaemic infarct. MATERIAL AND METHODS: Seventy-one patients with ischaemic
      stroke and 41 controls were studied. All patients had computed tomography of the
      brain performed after admission and on the third day and volume of the infarct
      was assessed by the volumetric method from the second examination. NSE and S 100B
      protein were analysed by immunochemiluminescence on the fourth day after
      admission. Clinical state of the patients was determined with the NIH stroke,
      Barthel and Rankin scales on admission, discharge from the hospital, and after
      one and 3 months from the onset of stroke. RESULTS: NSE levels in blood were
      significantly higher in stroke patients than in the control group - 36.9 +/- 24.0
      vs. 14.3 +/- 9.7 MUg/L. Also, the levels of the S 100B protein were significantly
      higher in the patient group (0.85 +/- 1.74 vs. 0.10 +/- 0.03 MUg/L) but only the
      levels of S 100B protein correlated with the calculated size of the infarct
      (Spearman coefficient = 0.77). No such correlation was identified for NSE level
      (Spearman coefficient = 0.25). CONCLUSIONS: Although significant differences in
      NSE and S 100B levels between stroke patients and the control group were found,
      only S 100B protein level correlated with stroke volume, neurological status at
      admission and functional outcome. NSE did not correlate with stroke volume,
      neurological status or clinical outcome.

PMID- 21082488
TI  - Medial sphenoid ridge meningiomas: early and long-term results of surgical
      removal using the fronto-temporo-orbito-zygomatic approach.
AB  - BACKGROUND AND PURPOSE: The fronto-temporo-orbito-zygomatic approach (FTOZA) is
      an alternative to the pte-rional approach in surgical resection of meningiomas of
      the medial part of the lesser wing of the sphenoid bone. The purpose of this
      study is to present our results of treatment of these meningiomas using the
      FTOZA. MATERIAL AND METHODS: Thirty patients (19 women, 11 men) with a central
      skull base tumour were included in the study. The neurological status of the
      patients was assessed before and after surgery as well as at the conclusion of
      treatment. The approximate volume of the operated tumour, its relation to large
      blood vessels, cranial nerves and brainstem, as well as consistency and
      vascularisation were assessed. RESULTS: The symptom duration ranged from 1 to 36
      months (median: 6 months). Impaired visual acuity was the predominant symptom in
      27.5% of patients. Less frequent symptoms included paresis/paralysis of the third
      cranial nerve, headache, psychoorganic syndrome and epilepsy. Approximate volume
      of the tumours ranged from 5 to 212 mL (median: 63 mL). Total or subtotal
      resection was achieved in 77% of patients. The postoperative performance status
      improved in 16.5%, did not change in 52.8% and deteriorated in 26.4% of patients.
      One (3.3%) patient died after the surgery. CONCLUSION: The FTOZA is a useful
      technique for removal of tumours expanding superiorly to the middle cranial fossa
      base without significant compression of the brain. Ability to remove tumours
      through the described approach decreases as the degree of infiltration of the
      clivus increases.

PMID- 21082489
TI  - [New guidelines for the treatment of neuropathic pain].

PMID- 21082490
TI  - Selected aspects of the epidemiology of multiple sclerosis in Poland - a
      multicentre pilot study.
AB  - BACKGROUND AND PURPOSE: The aim was to conduct a pilot study of selected
      epidemiological aspects of multiple sclerosis (MS) in Poland. MATERIAL AND
      METHODS: Cross-sectional data were collected in 21 centres providing MS
      treatment. The demographic profile of the patients, medical history of MS,
      disability status, comorbidity, and diagnostic and treatment modalities were
      analysed. RESULTS: Data on 3581 patients were obtained, including 2494 women
      (69.6%) and 1030 men (28.8%) - sex ratio 2.4 : 1. The mean age was 40.7 +/- 11.9
      years. Monofocal onset was reported in 80.8% of cases - the most frequently
      reported location of lesions was supratentorial (36.1%), followed by optic nerves
      (26.5%) and spinal cord (20.1%). The mean disease duration was 10.2 +/- 8.8 years
      (range 0.04-53 years), and the mean time from the first symptoms to MS diagnosis
      was 2.6 years. Relapsing-remitting MS was reported in 70.5% of patients,
      secondary progressive in 16.8%, primary progressive in 8.4%, and 'benign MS' in
      2.5%. The mean EDSS score was 3.3 +/- 2.2 (range 0-9.5). The family history of MS
      was positive in 6.4% of cases. Comorbidity mainly applied to the musculoskeletal
      system (6.5%), the urinary system (5.8%) and psychiatric disturbances (5.5%).
      Brain magnetic resonance studies were available in 96.3% of the patients, evoked
      potentials in 54%, and cerebrospinal fluid testing in 63.1% - of whom only 41.2%
      were tested for oligoclonal bands, with 84% of samples being positive.
      Immunomodulatory drugs were used in 842 patients (24%), predominantly interferon
      beta (81%) and glatiramer (13%). Mitoxantrone was the most commonly used
      immunosuppressant. CONCLUSIONS: This project is the first countrywide large-scale
      MS survey, covering approximately 18% of patients, according to our estimates.
      The results identify the clinical condition of the patients, as well as
      diagnostic and treatment modalities.

PMID- 21082491
TI  - The C242T polymorphism of the gene encoding cytochrome b-245 alpha is not
      associated with paediatric ischaemic stroke: family-based and case-control study.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species play an important role in the
      physiology and pathology of cerebral arteries, including ischaemic stroke. The
      cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain
      (p22phox peptide), a critical element of NAD(P)H oxidases, the most important
      source of superoxide anion in the cerebral arteries. To search for genetic
      factors associated with paediatric ischaemic stroke, the possible association
      between CYBA gene C242T polymorphism and the disease was evaluated. MATERIAL AND
      METHODS: The study group consisted of 238 individuals: children with ischaemic
      stroke (n = 70), their biological parents (n = 118) and children without any
      symptoms of stroke (n = 50). The C242T polymorphism was genotyped using
      polymerase chain reaction - restriction fragment length methodology. To evaluate
      the possible association between polymorphism and stroke, the transmission
      disequilibrium test and the case-control method were applied. RESULTS: The C242
      allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed
      frequencies did not differ significantly from expected (p = 0.10). There were
      also no significant differences in allele and genotype distribution between
      patients and control subjects (patients: CC - 50.0%, CT - 38.6%, TT - 11.4% vs.
      controls: CC - 52.0%, CT - 36.0%, TT - 12.0%). CONCLUSIONS: The study did not
      show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic
      stroke in children.

PMID- 21082492
TI  - Early rehabilitation of comatose patients after traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: As a result of improvements in the rescue system and
      progress in intensive care therapy, an increasing number of patients have
      survived severe traumatic brain injury in recent years. Early and consistent
      administration of the correct rehabilitation programme is of crucial importance
      for the restoration and improvement of cerebral function, as well as social
      reintegration. This prospective study was conducted at the neurosurgical
      department of a university hospital to assess the one-year outcome of comatose
      patients after severe traumatic brain injury. MATERIAL AND METHODS: Twenty-seven
      patients were included. Patients received multimodal early-onset stimulation and
      continuous inpatient and outpatient rehabilitation therapy. One-year outcome was
      assessed by means of the Glasgow Outcome Scale, Barthel Index, Functional
      Independence Measure (FIM) and need of care. RESULTS: Seven patients died, 4
      remained in a vegetative state, 7 were severely disabled, 6 were moderately
      disabled, and 3 achieved a good recovery 12 months after injury. Median Barthel
      Index was 65 and median FIM score was 84. The majority of patients were still at
      least intermittently dependent on care. CONCLUSION: Despite intensive
      rehabilitation treatment, severe traumatic brain injury is still burdened with
      significant mortality and morbidity.

PMID- 21082493
TI  - [The role of skeletal muscle biopsy in the diagnosis of neuromuscular disorders].
AB  - Muscle biopsy is required to provide a definitive diagnosis in many neuromuscular
      disorders. Biopsy findings may indicate whether the pathological process is of
      neurogenic or myopathic origin. The muscle biopsy may give important information
      on the course of the disease (acute or chronic) and on the disease stage and
      progression. The interpretation of muscle biopsy, including histochemical and
      ultrastructural analysis, is a key factor in the diagnosis of muscular
      dystrophies, glycogenoses, inflammatory myopathies and congenital myopathies. An
      assessment of muscle biopsy on electron microscopy enables a definite diagnosis
      of oculopharyngeal muscular dystrophy, mitochondrial myopathy or inclusion body
      myositis. This paper presents an overview of general indications for muscle
      biopsy, biopsy procedures, as well as transportation and preparation of muscle
      tissue for final microscopic analysis. The interpretation of specific microscopic
      findings and a brief discussion on the clinical usefulness of muscle biopsy in
      the era of molecular diagnosis are also presented.

PMID- 21082495
TI  - [Advances in treatment of fragile X syndrome].
AB  - The fragile X syndrome (FRAX) is the most common familial form of mental
      retardation. The incidence is estimated at 1 in 4000 males. The leading symptom
      of the syndrome is mental retardation, with accompanying behavioural problems.
      About 25-35% of affected persons meet the criteria of autism. The behavioural
      problems involve attention problems, hyperactivity, tactile defensiveness, speech
      problems (echolalia), aggression, emotional problems, depression, anxiety, and
      stereotypic movements. There is no causal treatment and management is mainly
      symptomatic. Many specialists should be involved in this process. Behavioural and
      educational therapy is indicated. The basic step is identification of the child's
      problems. Its goal is to promote development of the child's abilities.
      Pharmacological intervention should be accompanied by supporting methods. The
      diagnosis of FRAX involves the entire family. The family members should be
      offered genetic counselling and the possibility of diagnostic DNA analysis.

PMID- 21082494
TI  - [Fronto-temporo-orbito-zygomatic approach - analysis of the surgical technique on
      cadaver simulations].
AB  - This paper presents consecutive stages of the fronto-temporo-orbito-zygomatic
      approach (FTOZA). Two simulations of FTOZA were performed on non-fixed human
      cadavers without any known pathologies in the head and neck. The consecutive
      stages of the procedure were documented with photographs and schematic diagrams.
      The starting point for FTOZA is a pterional craniotomy and osteotomy including
      the orbital rim, body of the zygomatic bone and zygomatic arch. In justified
      cases it is also possible to temporarily remove the upper and lateral walls of
      the orbit. Wide drawing apart of the Sylvian fissure is an important supplement
      of the approach. The fronto-temporo-orbito-zygomatic approach is a reproducible
      technique, which provides surgical penetration of the middle cranial fossa and
      related regions. This approach is particularly useful in the treatment of tumours
      of the above-mentioned anatomical areas as well as vascular malformation of the
      posterior part of the arterial circle of the brain.

PMID- 21082496
TI  - PLP1 gene duplication as a cause of the classic form of Pelizaeus-Merzbacher
      disease - case report.
AB  - Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelination disorder of
      the central nervous system (CNS). PMD is caused by mutations in the PLP1 gene
      located at Xq22 and encoding the major myelin component in CNS, proteolipid
      protein 1 (PLP1). The disease is clinically heterogeneous. Phenotypes are
      generally categorized into classic and connatal forms. Connatal PMD has more
      rapid progression with early death, while patients with classic PMD generally
      survive to adulthood. Both forms of the disease are caused by point mutations as
      well as rearrangements - multiplication (mainly duplication) and deletion of the
      PLP1 gene. We present a case of a male patient affected by the classic form of
      PMD with benign course, except severe dysarthria with the characteristic
      laryngeal stridor, which is more typical for connatal form of the disease. The
      diagnosis has been confirmed at the molecular level. The patient has duplication
      of all 7 exons of the PLP1 gene. This duplication was inherited from the
      patient's mother, who is an unaffected carrier of the mutation. The patient's
      family pedigree analysis revealed the interfamilial variability of the phenotype
      among affected male relatives.

PMID- 21082497
TI  - Brucellar discitis as a cause of lumbar disc herniation: a case report.
AB  - Brucellosis is an infectious disease spread by consumption of non-pasteurized
      milk products or through contact with infected animals. Spinal involvement is one
      of the most important complications and the lumbar area is the most frequently
      affected site. Among the neurological consequences, nerve root compression can be
      a result of epidural abscess, granuloma or discitis secondary to vertebral body
      involvement. In this case report we present a 50-year-old male patient with
      brucellar discitis without spondylitis which caused lumbar disc herniation. We
      want to emphasize that discitis should also be considered in differential
      diagnosis of nerve root compression in suspected cases.

PMID- 21082500
TI  - Ovarian hyperstimulation syndrome: a preventable syndrome?

PMID- 21082498
TI  - Pituitary apoplexy after cardiac surgery in a patient with subclinical pituitary
      adenoma: case report with review of literature.
AB  - We report a case of pituitary apoplexy occurring in a 74-year-old patient 6 hours
      after cardiac surgery. The patient presented with confusion, unilateral ptosis
      and ophthalmoplegia. Neurological examination revealed right oculomotor nerve
      palsy and decreased level of consciousness. Magnetic resonance imaging showed a
      hemorrhagic and necrotic pituitary macroadenoma. After prompt endocrinological
      replacement therapy with hydrocortisone and levothyroxine, the confusion of the
      patient resolved. Removal of a non-functional macroadenoma with large necrotic
      areas resulted in full recovery. The physician should be aware of pituitary
      adenoma infarction after open cardiac surgery and should remember that it can be
      fatal or cause permanent neurological or endocrine damage without proper
      treatment. Surgical and endocrine treatment can be life-saving procedures.

PMID- 21082501
TI  - Ovarian hyperstimulation syndrome: definition, incidence, and classification.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a iatrogenic complication of
      controlled ovarian stimulation. Although considered uncommon, the severe form is
      potentially fatal. Different clinical classifications have been developed through
      the years. No matter whether it is termed "grade C" or "critical" OHSS, life
      threatening events may develop. Hence it is prudent to recognize the population
      at risk. Several risk factors for OHSS have been identified; some are considered
      major risk factors such as polycystic ovary syndrome; others are less well
      defined. Preventive measures could be taken before and during the treatment cycle
      while taking into consideration the patient's characteristics and the various
      treatment options and approaches that currently exist.

PMID- 21082502
TI  - Physiology and pathology of ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle
      stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human
      chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying
      this clinical picture is increased vascular permeability (VP). With the
      administration of hCG, the expression vascular endothelial growth factor (VEGF)
      and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum
      coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and
      VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire
      corpus luteum. These findings suggest that the syndrome can be prevented by
      inducing ovulation with LH or gonadotropin-releasing hormone analogs, which
      prevent VEGF overexpression. Also, coadministration of a dopamine agonist
      inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors,
      the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and
      44% with a placebo ( P = 0.04). Another dopamine agonist, quinagolide, was also
      effective in nonpregnant patients, but those pregnant did not benefit from
      dopamine agonist administration. In conclusion, the pathophysiological mechanisms
      involved in OHSS show that targeting VEGF/VEGFR2 is an effective preventive
      approach to treat the syndrome. Pharmaco-prevention through dopamine agonists is
      effective only in nonpregnant high-risk OHSS women. Embryo cryopreservation plus
      dopamine agonist administration might be the most appropriate way to prevent OHSS
      in high-risk patients.

PMID- 21082503
TI  - Identification of the high-risk patient for ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication of ovarian
      stimulation for assisted reproduction, is a potentially life-threatening
      condition. Exogenous human chorionic gonadotropin (hCG) administered for final
      oocyte maturation and endogenous hCG produced by a developing pregnancy are
      fundamental in the development of the disease. Vascular endothelial growth factor
      is the key molecule mediating the pathophysiology of the syndrome, and genetic
      predisposition might play a role. Because the most severe cases are usually the
      late OHSS cases that occur when a pregnancy is established, several predictive
      markers have been introduced to identify the high-risk patient profile and
      consequently develop preventive strategies. This article reviews the most recent
      evidence evaluating the accuracy of different OHSS prediction parameters.
      Stratification was attempted according to the phase of the ovarian stimulation
      that the patients undergo. Anti-Mullerian hormone and the number of follicles
      seen on ultrasound seem promising discriminating factors, whereas prediction
      models that include age, antral follicle count, and estrogen levels on the day of
      ovulation triggering provide variable sensitivity and specificity. Until reliable
      genetic tests are available, and considering that the occurrence of pregnancy is
      unpredictable, the use of prognostic factors will be mainly indicative of risk
      rather than preventive of OHSS.

PMID- 21082504
TI  - Ovarian hyperstimulation syndrome prevention strategies: individualizing
      gonadotropin dose.
AB  - The choice of the gonadotropin starting dose is an important parameter to prevent
      the onset of ovarian hyperstimulation syndrome (OHSS). The vast majority of
      studies available propose decreasing the gonadotropin starting dose, but
      conflicting results confirm that simply reducing the dose is not sufficient to
      prevent OHSS. True and dependable individualization of the gonadotropin starting
      dose is not yet possible. Attempts have been made to select parameters that
      predict ovarian response and to model them in a scoring system or algorithm that
      would result in a recommended gonadotropin starting dose. The CONSORT
      (CONsistency in r-FSH Starting dOses for individualized tReatmenT) dosing
      algorithm individualizes recombinant human follicle-stimulating hormone doses for
      assisted reproduction technologies, assigning 37.5-IU increments according to
      easily available patient characteristics (basal follicle-stimulating hormone,
      body mass index, age, and antral follicle count) that have been proven to
      accurately predict ovarian response to ovarian stimulation. The use of the
      CONSORT algorithm achieved an adequate oocyte yield and good pregnancy rates in a
      preliminary study. Results of a prospective randomized study are awaited to see
      if this tool would allow individualization of the gonadotropin starting dose.

PMID- 21082505
TI  - Ovarian hyperstimulation syndrome prevention strategies: oral contraceptive pills
      dual gonadotropin-releasing hormone agonist suppression with step-down
      gonadotropin protocols.
AB  - The identification of patients at high risk for excessive responses to ovarian
      stimulation for in vitro fertilization and embryo transfer is essential in the
      tailoring of safe and effective treatment strategies. Known factors associated
      with increased sensitivity to gonadotropins include polycystic ovary syndrome,
      young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral
      follicle count, and high baseline ovarian volume. Although several treatment
      strategies have been proposed for these patients, this report describes the
      experience using the dual suppression with gonadotropin step-down protocol. This
      protocol uses oral contraceptive pretreatment in combination with a long
      gonadotropin-releasing hormone agonist followed by a programmed step-down in
      gonadotropin dosing. Hormonal characteristics of dual suppression include an
      improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower
      serum androgens, particularly dehydroepiandrosterone sulfate. Clinical
      characteristics of the protocol include a lower cancellation rate and favorable
      clinical and ongoing pregnancy rates per initiated cycle while mitigating the
      risk of OHSS.

PMID- 21082506
TI  - Ovarian hyperstimulation syndrome prevention strategies: reducing the human
      chorionic gonadotropin trigger dose.
AB  - This article reviews the biological plausibility and evidence for the use of a
      low triggering dose of human chorionic gonadotropin (hCG) in the prevention of
      ovarian hyperstimulation syndrome (OHSS). A systematic search of the literature
      revealed very little published data for or against the use of low-dose hCG in the
      prevention of OHSS after assisted reproductive technology. We have had success at
      avoiding OHSS as a result of gentle stimulation and low-dose sliding scale hCG
      trigger based on estradiol (E2) levels. We therefore present the biological
      plausibility for such an approach by reviewing the relationship between OHSS,
      vascular endothelial growth factor, and hCG; the physiology of hCG; the
      relationship between risk of OHSS and E2 at trigger; and the physiology of
      alternative methods of triggering such as recombinant luteinizing hormone and
      gonadotropin-releasing hormone agonist. We also present the results of a quasi
      experimental before and after study of the sliding scale protocol for hCG trigger
      dose in in vitro fertilization with or without intracytoplasmic sperm injection
      cycles.

PMID- 21082507
TI  - Withholding gonadotropins until human chorionic gonadotropin administration.
AB  - Withholding gonadotropins in women who exhibit high estradiol responses before
      follicles reach full maturation is called "coasting." Coasting, or suspending
      gonadotropin administration, can be an effective strategy for decreasing the risk
      of ovarian hyperstimulation syndrome (OHSS) while reducing cancelation rates. In
      in vitro fertilization cycles, mechanistically it is believed that withholding
      gonadotropins starves smaller follicles, induces apoptosis, and decreases the
      potential for these follicles to elaborate vascular endothelial growth factor, a
      known mediator of OHSS. It is generally accepted that coasting should be
      initiated when the estradiol (E2) level is >3000 pg/mL in the setting of immature
      follicles. The human chorionic gonadotropin (hCG) trigger should be administered
      when the E2 level subsequently drops to a "safe" level. Cycle cancellation should
      be considered if, after 3 to 4 days of coasting, the E2 level remains excessively
      elevated. Oocyte retrieval may also be cancelled if the E2 level on the day after
      hCG trigger drops precipitously. In gonadotropin-releasing hormone agonist
      (GnRHa)-based protocols, one can consider withholding GnRHa administration if the
      E2 level continues to increase after a few days of coasting. Current data seem to
      show that the coasting period is short and/or is less likely to be required in
      GnRH-antagonist protocols as compared with GnRHa-based protocols. Large
      randomized control trials are still needed to establish the relative efficacy of
      coasting versus embryo cryopreservation in the context of OHSS prevention.

PMID- 21082508
TI  - Ovarian hyperstimulation syndrome prevention strategies: use of gonadotropin
      releasing hormone antagonists.
AB  - The most serious complication of ovarian stimulation for in vitro fertilization
      is severe ovarian hyperstimulation syndrome (OHSS), a rare but potentially life
      threatening condition. The present review discusses the place of gonadotropin
      releasing hormone antagonists (GnRH-ant) in primary, secondary, and tertiary
      prevention of OHSS. Sound evidence indicates that the routine use of GnRH-ant
      instead of GnRH agonists (GnRHa) during ovarian stimulation drastically reduces
      the relative risk of OHSS. GnRH-ant are therefore useful for primary OHSS
      prevention, and an increased use of antagonists should help reduce the overall
      incidence of severe OHSS with its associated risks and complications. In patients
      on antagonist protocols identified to be at risk of developing severe OHSS,
      replacing human chorionic gonadotropin with GnRHa as a trigger of final oocyte
      maturation has been proposed as an effective measure of secondary prevention. A
      concept of combining GnRHa triggering with cryopreservation of all oocytes or
      embryos has yielded promising results as far as total avoidance of OHSS is
      concerned while providing a good chance of pregnancy for the patient in later
      frozen-thawed embryo transfers. In patients with early onset of OHSS,
      reinitiation of GnRH-ant in the luteal phase as a measure of tertiary prevention
      might lead to rapid regression of the syndrome; however only limited data on this
      new concept are available in the literature.

PMID- 21082509
TI  - Gonadotropin-releasing hormone agonist trigger: the way to eliminate ovarian
      hyperstimulation syndrome--a 20-year experience.
AB  - Gonadotropin-releasing hormone agonist (GnRHa) trigger instead of human chorionic
      gonadotropin in the context of ovarian hyperstimulation syndrome (OHSS)
      prevention has been used for >20 years. In its first decade it did not gain
      popularity because it cannot work in GnRHa-based ovarian stimulation protocols.
      The introduction of GnRH antagonists has revolutionized our ability to eliminate
      OHSS completely because patients at high risk for OHSS can be triggered with
      GnRHa. This has been documented in randomized prospective studies, in which none
      of the patients randomized to the agonist trigger arm developed OHSS. In other
      words, GnRHa proved to be a potent tool that, truly remarkably, never fails.
      Although there is some debate concerning the clinical outcome of these cycles,
      data so far indicate that aggressive luteal support can ensure a good outcome.
      Moreover, the large number of frozen embryos in these cycles results in excellent
      per-oocyte retrieval pregnancy rates. In summary, GnRHa ovulatory trigger is the
      ultimate tool for complete OHSS prevention. GnRH antagonist-based ovarian
      stimulation protocols should be considered in OHSS high-risk patients so GnRHa
      trigger can be used if needed.

PMID- 21082510
TI  - Ovarian hyperstimulation syndrome prevention strategies: Luteal support
      strategies to optimize pregnancy success in cycles with gonadotropin-releasing
      hormone agonist ovulatory trigger.
AB  - Gonadotropin-releasing hormone agonist (GnRHa) administration for the induction
      of oocyte maturation during in vitro fertilization treatment is effective in the
      prevention of ovarian hyperstimulation syndrome (OHSS). However, some studies
      have reported a lower ongoing pregnancy rate after GnRHa trigger. The excellent
      conception rates reported in recipients receiving embryos originating from donor
      cycles or in women receiving frozen embryos originating from fresh cycles during
      which GnRHa was used to induce oocyte maturation suggest that it does not
      adversely affect the quality of the oocyte or embryo. A defective corpus luteum
      function resulting from the relatively short endogenous luteinizing hormone surge
      may be detrimental to endometrial receptivity. Aggressive luteal phase support
      and monitoring is therefore essential in view of the overwhelming evidence
      suggestive of abnormal luteal phase steroid profile. This may be achieved by the
      use of adequate estradiol and progesterone supplementation in the luteal phase
      and the first trimester. An alternative approach is the use of adjuvant low-dose
      human chorionic gonadotropin, although caution should be exercised in view of the
      associated risk of OHSS development.

PMID- 21082511
TI  - Ovarian hyperstimulation syndrome prevention strategies: cryopreservation of all
      embryos.
AB  - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic potentially life
      threatening condition resulting from excessive ovarian stimulation. The crucial
      event in the development of OHSS is the administration of human chorionic
      gonadotropin (hCG). The early onset of OHSS typically presents in the luteal
      phase as a consequence of ovulatory hCG. The late onset of OHSS presents in early
      gestation when endogenous hCG further stimulates the ovary. Many strategies have
      been proposed for OHSS prevention, but they may reduce but not eliminate the
      risk. This article reviews the evidence related to the elective cryopreservation
      of all embryos and their subsequent transfer in women at risk of OHSS. More
      research is needed to determine whether using elective cryopreservation of
      embryos can reduce the rate of severe OHSS in in vitro insemination
      (IVF)/intracytoplasmic sperm injection (ICSI). Results from many retrospective
      studies are encouraging, but prevention in terms of (1) identification of the
      high-risk population using new biochemical markers of ovarian response such as
      anti-Mullerian hormone, (2) tailoring ovarian stimulation and using less
      aggressive protocols (gonadotropin-releasing hormone antagonists or mild IVF),
      and (3) blastocyst culture to allow clinical monitoring of early-onset OHSS, with
      eventual blastocyst cryopreservation, might represent a multistep approach worth
      further investigation.

PMID- 21082512
TI  - Treatment of ovarian hyperstimulation syndrome.
AB  - Mild forms of ovarian hyperstimulation syndrome (OHSS) do not require treatment.
      Moderate OHSS should be followed up on an outpatient basis with no specific
      treatment. Severe OHSS requires proper evaluation. Investigations are done to
      evaluate hematocrit, electrolytes, and kidney and liver function. Conservative
      treatment with intravenous (i.v.) fluids and close monitoring is usually done.
      Intensive care admission is indicated in cases with severe respiratory distress
      or major electrolyte imbalance with elevated serum creatinine. Crystalloids in
      the form of i.v. saline and colloids as albumin or hydroxyethyl starch are
      commonly used to expand intravascular volume. Dopamine can be used to improve
      diuresis, and prophylactic heparin is administered to prevent venous thrombosis.
      Diuretics are generally contraindicated because they may further contract
      intravascular volume. Abdominal or vaginal aspiration of ascitic fluid results in
      marked improvement of symptoms, improved diuresis, and shortened hospital stay.
      The current trend to treat patients with i.v. fluids, albumin, and to perform
      aspiration of ascitic fluid on an outpatient basis has been found to be a more
      cost-effective protocol of treatment.

PMID- 21082513
TI  - An eye to the future.

PMID- 21082515
TI  - [Non-bacterial cystitis: principles, diagnostics and etiogenic therapy options].
AB  - The therapy for non-bacterial cysitides is often based on purely symptom-oriented
      measures which in many cases relieve the patient's symptoms but cannot stop the
      chronic progression of the disease. The present article summarises the most
      common forms of non-bacterial cystitis (interstitial, radiogenic, chemotherapy
      induced) with their common pathophysiology and then introduces the most common
      therapeutic procedures. With regard to radiogenic and chemotherapy-induced
      cystitis it must be considered that optimal preventative measures can often
      markedly delay or even prevent the development of the inflammatory processes. The
      preventative therapeutic measures mentioned in this article should thus
      constitute a fixed part of the accompanying therapy within the framework of
      tumour-related treatment. As alternatives or supplements to symptomatic therapy,
      causal therapy options show good response rates. Besides successful hyperbaric
      oxygen therapy, this also holds for hyalurane that is instilled with the aim of
      repairing the damaged glycosamine layer in the endothelium of the urinary bladder
      and so opens new curative options in cases that were previously considered as
      therapy resistant. A prior potassium-sensitivity test is recommended as this
      allows the putative success of the therapy to be predicted with a high
      probability. However. It is equally important, especially in cases of
      interstitial cystitis, that the diagnosis is made as early as possible which was
      often not done in the past.

PMID- 21082514
TI  - Magnetic resonance imaging of rare intracranial neoplasms--role of the in vivo 1
      h spectroscopy in the radiological differential diagnostics.
AB  - BACKGROUND: The object of this study was to evaluate the usefulness of magnetic
      resonance (MR) spectroscopy in differentiating rare intracranial tumours in adult
      patients. Review of the literature on results of MR spectroscopy in these lesions
      is also included. MATERIAL AND METHOD: 89 patients with brain tumours were
      evaluated preoperatively with in vivo 1.5 T MR spectroscopy (according to eTumour
      study requirements). 8 of them were diagnosed as having very rare neoplasms:
      haemangiopericytoma (2), lymphoma (2), plexus papilloma (2), chondroma (1) and
      purkinjoma (1). Spectra of these tumours were compared to spectra of common brain
      tumours that could resemble these lesions. RESULTS: MR spectroscopy enabled
      discrimination between meningiomas and haemangiopericytomas, meningiomas and
      lymphomas, and purkinjomas or chondromas and other brain tumours. The method was
      unreliable in distinguishing between glioblastomas and lymphomas. CONCLUSION: The
      small number of patients made statistical analysis impossible. However, at
      present, it seems that neuroradiological diagnosis should not rely on MR
      spectroscopy alone.

PMID- 21082516
TI  - [Differential indications in hydrocele operations - a contribution to prophylaxis
      for recurrent hydrocele].
AB  - BACKGROUND: In the operative treatment of idiopathic hydroceles the available
      techniques are frequently not selected as indicated according to the different
      expansions of hydroceles but rather the accustomed procedures are used. MATERIAL
      AND METHODS: In a retrospective analysis the methods and complications of
      hydrocele operations were evaluated. RESULTS: From 1988 to 2008 195  hydroceles
      in 191  patients were operated upon: 22 (11.3 %) by eversion (according to
      Jaboulay), 27 (13.8 %) by resection (according to von Bergmann) and 146 (74.9 %)
      by a combination of resection and eversion (according to Kocher) of the tunica
      vaginalis communis. In 14 (7.2 %) patients the operation was indicated by a
      recurrent hydrocele, either after an eversion alone (n = 7) or after an
      insufficient resection (n = 7) of the tunica vaginalis communis. As complications
      of the operation an abscess occurred in 4 (21 %) cases, a haematoma in 5 (2.6 %)
      cases and a combination of both had to be reoperated in 2 (1.0 %) cases.
      CONCLUSIONS: In order to prevent recurrent hydroceles the available methods for
      the operative treatment of idiopathic hydrocele should be selected according to
      the different expansions of the hydroceles and as such consequently executed.

PMID- 21082517
TI  - [Urinary bladder tuberculosis and bacillus calmette-guerin instillation: reduced
      efficacy of bisoprolol in hypertension].
AB  - HISTORY AND ADMISSION FINDINGS: A 71-year-old patient with a superficial
      carcinoma of the urinary bladder and high risk of recurrence was treated with
      intravesical instillation of Bacillus Calmette-Guerin (BCG) after transurethral
      resection. As a complication of the catheterization during BCG-instillation
      therapy the patient suffered from tuberculosis. The patient received a
      tuberculosis triple-therapy including rifampicin 600 mg once daily, isoniazid 300
      mg once daily and ethambutol 400 mg thrice daily. The existing arterial
      hypertension had successfully been controlled by 3.75 mg bisoprolol medication
      once daily for the last 15  years. An increase of blood pressure and cardiac
      arrhythmia were seen after combining the beta (1)-receptor blocker treatment with
      the triple-therapy. INVESTIGATIONS AND DIAGNOSIS: The blood pressure was 160 / 90
      mmHg. The heart rate reflected a value of 98  beats per minute. In the resting
      ECG monotopic ventricular extrasystoles could be diagnosed. TREATMENT AND COURSE:
      The dosage of bisoprolol was changed to 3.75 mg in the morning and additional
      1.875 mg in the evening. Due to this increase of dosage the blood pressure could
      be controlled sufficiently. CONCLUSION: Rifampicin is one of the best known
      potent enzyme inducing drugs. It strongly induces the expression of cytochrome
      P450 3A4 in the liver. The enzyme induction enhance the hepatic bisoprolol
      metabolism, hence the metabolic clearance of the drug increased. The maximal
      plasma level of bisoprolol decrease and in our use the arterial hypertension
      could not be treated sufficiently. It is well known that half the dose of
      bisoprolol undergoes oxidative metabolism in the liver and the rest eliminated
      unchanged in the kidney. A dosage adjustment of bisoprolol is necessary if the
      clinical status of the patient requires treatment with the antituberculosis drug
      rifampicin.

PMID- 21082518
TI  - [Phyllodes tumour of the seminal vesicle - case report of a rare tumour entity].
AB  - Neoplasms of the seminal vesicles are rare. Here we report on a patient with a
      low-grade phyllodes tumour of the seminal vesicle. The patient was admitted to
      our hospital with a tumour in the excavatio rectovesicalis diagnosed by CT scan.
      He had no symptoms. For further diagnosis we took transrectal ultrasound-guided
      biopsies, the histopathological examination showed no malignant features. One
      month later a follow-up CT scan demonstrated a significant enlargement of the
      tumour. Therefore we decided to perform a surgical exploration. During surgery we
      found a partially necrotic mass involving the prostate, the urinary bladder and
      the rectum. Both radical cystoprostatectomy with ileal conduit and anterior
      resection of the rectum with colostomy were necessary. Histologically the
      specimen showed a low-grade phyllodes tumour of the left seminal vesicle. One
      year after surgery the follow-up was completely normal without any residual or
      recurrent tumour. Frequency, histology, diagnostic investigations, therapy and
      prognosis of this rare tumour entity are discussed with respect to the actual
      literature.

PMID- 21082519
TI  - [Psychosomatic aspects of chronic recurrent cystitis].
AB  - INTRODUCTION: In spite of intensive research, chronic recurrent cystitis is
      etiologically a still insufficiently understood clinical picture. CASE REPORT: A
      52-year-old patient presented with recurrent cystitis that had been treated
      exclusively somatically for years for which at least a psychosomatic co
      pathogenesis of magnitude of the discomfort was diagnostically representable as
      well as being of therapeutic utility. CONCLUSION: In recollection of a bio
      psychosocial understanding of human diseases, psychosomatic considerations should
      be undertaken at last but not least in patients with persistent cystitis.

PMID- 21082522
TI  - [DIVI Congress 2010: Living interdisciplinary intensive care].

PMID- 21082520
TI  - [Ureterorenoscopy with calculus removal and lithotripsy].

PMID- 21082523
TI  - [Neurological intensive care: Progress and problems].

PMID- 21082524
TI  - [Renal replacement therapy in acute renal failure].
AB  - Acute kidney injury (AKI) is characterized by a sudden breakdown of the
      incretoric and excretoric functions of the kidneys. In intensive care it is
      always part of a multiple organ failure (MOF). It has a high incidence in
      intensive care (5 - 20 %), increasing up to 50 % in patients with septic shock.
      Its prognosis is variable (mortality 20 - 80 %) due to the fact, that up to the
      establishing of RIFLE and AKIN no consistent classification existed. Early start
      of extracorporeal treatment may lead to a reduced mortality in critically ill
      with AKI and MOF as the negative influence of AKI on other vital function
      disturbances may be reduced. Independent of the treatment form, all critically
      ill need a dosage of dialysis enabling negative effects of the hypercatabolic
      situation for these patients. An increase of the dosage over these demands did
      not lead to a better survival in the inhomogeneous group of all patients with AKI
      and MOF. In continuous forms of treatment an exchange amount of 20 ml/kg/h should
      be reached, as in intermittent hemodialysis a Kt/V lower 4 - 4.5/week should be
      avoided. According to the survival of the patients there is no evidence that
      either continuous forms of treatment or intermittent dialysis is superior over
      the other, comparing always these heterogeneous groups of medical and surgical
      AKI patients. There seems to be a small group of patients (mortality > 80 %)
      never included in any prospective randomized trial which can only be treated
      continuously.

PMID- 21082525
TI  - [Heart-brain interaction in intensive care medicine].
AB  - Cardial diseases are common causes of neurological emergencies. On the other
      hand, acute neurological disorders go along with systemic abnormalities, in
      particular they show cardial and pulmonary complications. This review is focused
      on the cardial consequences of cerebral lesions. Independent on the etiology of
      the brain disorder, the central activation of the adrenergic system plays a key
      role in the pathophysiology. The adrenergic stimulation modulates cardial
      function. ECG-changes, elevated cardial enzymes, arrhythmias, and sudden cardial
      death can be the consequences. In these cases, the adequate treatment of the
      neurological disorder is essential for the improvement of systemic symptoms. The
      cardial disorders (apical ballooning cardiomyopathy, neurogenic pulmonary edema)
      then have a favourable prognosis. For future studies on treatment of neurogenic
      cardial disorders, the classification of the differently defined disorders based
      on their common pathophysiology will be essential.

PMID- 21082526
TI  - [Respiratory distress after insertion of a central venous line].

PMID- 21082527
TI  - [Therapeutic hypothermia after resuscitation].

PMID- 21082528
TI  - [Therapeutic hypothermia in neurological critical care].
AB  - Therapeutic hypothermia (TH) is very effective for the treatment of acute
      experimental brain injury. In contrast to other neuroprotective methods or
      pharmacological agents, TH represents the only clinically proven neuroprotective
      therapy. TH led to a decreased mortality rate and improved functional outcome in
      patients with cardiac arrest. Investigations in severe head trauma are
      inconclusive up to now. Other important indications such as ischemic stroke
      remain to be investigated properly. Recent phase II studies are on the way to
      test safety and feasibility in the early time window of stroke including
      thrombolysis. The recent article describes the status and perspectives including
      open questions for hypothermia in neurological intensive care.

PMID- 21082529
TI  - [Reversal of oral anticoagulation in intracranial hemorrhage].

PMID- 21082530
TI  - [Activated protein C in patients with septic shock: pro].

PMID- 21082531
TI  - [Activated protein C in patients with septic shock: contra].

PMID- 21082532
TI  - [Fibrinolysis as a therapeutic option in acute ST-elevation myocardial
      infarction].
AB  - The introduction of intravenous thrombolytic therapy started the new era of
      reperfusion therapy in ST elevation myocardial infarction. The addition of
      aspirin almost halved mortality in patients with ST elevation infarction. Primary
      coronary intervention (PCI) often in combination with stent implantation instead
      of thrombolytic therapy increases infracted-artery patency and reduces mortality,
      number of re-infarction and stroke even further. However, studies comparing the
      benefits of both therapeutic regimens often included patients with long symptom
      duration (up to 12 hours and more). In addition, there are differences in long
      term treatment after myocardial infarction in both groups since the addition of
      thienopyridines to standard treatment after stent implantation. The routine
      combination of thrombolytic therapy and immediate PCI (facilitated PCI) did not
      prove beneficial whereas a pharamacoinvasive strategy including thrombolytic
      therapy and PCI at a later time point could be beneficial. Subgroup analysis in
      the studies comparing PCI and thrombolytic therapy suggested a beneficial effect
      for patients receiving thrombolytic therapy early after symptom onset (>= 2 h).
      Therefore, a strategic concept of thrombolytic therapy early after symptom onset
      in patients presenting with ST elevation myocardial infarction combined with
      either rescue intervention when indicated or planned PCI is currently tested in
      the so STREAM-study (STrategic Reperfusion Early After Myocardial Infarction).
      Hopefully this study will clarify the role of thrombolytic therapy in ST
      Elevation myocardial infarction compared to PCI alone.

PMID- 21082533
TI  - Combination Therapy with Nateglinide and Telmisartan Ameliorates Insulin
      Resistance in Zucker Fatty Rats by Suppressing Advanced Glycation End Product
      Receptor Axis.

PMID- 21082535
TI  - The impact of assisted reproductive technology on the association between first
      trimester pregnancy-associated plasma protein a and human chorionic gonadotropin
      and adverse pregnancy outcomes.
AB  - We evaluated the impact of assisted reproductive technology (ART) on the
      association between first-trimester pregnancy-associated plasma protein A (PAPP
      A) and human chorionic gonadotropin (beta-hCG) and adverse pregnancy outcomes.
      PAPP-A and beta-hCG levels were obtained between 11 and 13 (6)/ (7) weeks'
      gestation and converted to multiples of the median (MoM). MoM < 5th percentile
      was defined as low PAPP-A or beta-hCG and those > 90th percentile as high.
      Adverse outcomes included small-for-gestational-age (SGA) infants, preeclampsia,
      pregnancy loss, and preterm delivery (PTD). Univariate and multivariate analyses
      were used to estimate the association. Of 4000 women meeting the inclusion
      criteria, 265 (7.6%) pregnancies were conceived by ART. ART pregnancies with low
      PAPP-A had a higher risk of having an SGA infant (odds ratio [OR] = 4.1, 95%
      confidence interval [CI] 1.2, 14.0) or PTD < 32 weeks (OR = 5.3, 95% CI 1.5,
      18.6) compared with non-ART pregnancies with low PAPP-A (OR = 2.8, 95% CI 1.7,
      4.7; OR = 3.9, 95% CI 2.1, 7.0, respectively). High PAPP-A was associated with
      pregnancy loss (OR = 6.1, 95% CI 1.1, 33.7) in ART pregnancies. Low beta-hCG was
      associated with increased risk for PTD only in ART pregnancies (OR = 8.3, 95% CI
      1.9, 35.9) for PTD < 37 weeks (OR 6.1, 95% CI 1.6, 23.0) for PTD < 35 weeks and
      (OR = 10.8, 95% CI 2.7, 43.7) for PTD < 32 weeks. High beta-hCG was associated
      with increased risk for SGA (OR = 1.6, 95% CI 1.0, 2.5) and PTD < 37 weeks (OR =
      1.4, 95% CI 1.0, 1.9) in non-ART pregnancies. The association between PAPP-A and
      beta-hCG with adverse pregnancy outcomes is influenced by the mode of conception.

PMID- 21082536
TI  - Computerized physician order entry reduces medication turnaround time of labor
      induction agents.
AB  - We sought to determine whether computerized physician order entry (CPOE) improves
      the induction agent turnaround time on the labor and delivery unit (L&D) compared
      with paper-based order entry (PBOE). We conducted a retrospective study of
      singleton, term pregnancies admitted to L&D for induction of labor. Outcomes of
      women who delivered 3 months before or 3 months after universal CPOE
      implementation were compared including induction agent turnaround time. The
      induction agent turnaround time was significantly shorter in the CPOE group ( N =
      83) compared with PBOE group ( N = 71) [71 (range 8 to 411) versus 100 (2 to 442)
      minutes, P = 0.004]. There were no differences in cesarean section rate or length
      of hospital stay. After controlling for time of day of induction, induction
      agent, and type of order entry, CPOE continued to significantly decrease the
      induction agent turnaround time by 25 minutes ( P = 0.042). CPOE improved the
      process of induction of labor and efficiency of care of pregnant women.

PMID- 21082537
TI  - Exchange of peripherally inserted central catheters is associated with an
      increased risk for bloodstream infection.
AB  - It is not uncommon that the peripherally inserted central catheter (PICC) needs
      to be replaced either due to blockage or migration to a peripheral position. In
      such circumstances, there are two methods of PICC placement: new-site insertion
      and exchange by using the old PICC as a guide wire. Our objective was to
      investigate risk of infection associated with the exchange method. In this
      retrospective study, data on all PICC insertions in the neonatal intensive care
      unit in 2004 to 2008 were obtained. In the population who needed removal of
      existing PICC and insertion of a new one, we compared central line-associated
      bloodstream infection (CLABSI) within 1 week of insertion between the two
      insertion methods. Of 1148 PICC insertions reviewed, 164 (103 new-site and 61
      exchange insertions) were performed after removal of a blocked/malpositioned PICC
      and therefore comprised the study population. The rate of CLABSI was higher in
      the exchange method (9.8% versus 1%, P < 0.007). After adjusting for the
      confounders, the odds for CLABSI within 7 days of PICC insertion was higher with
      the exchange method (odds ratio 25.2, 95% confidence interval: 2.17 to 292.98; P
      = 0.01). In infants, insertion of PICCs using the exchange method carries an
      increased risk of bloodstream infection.

PMID- 21082538
TI  - Maternal periodontal disease is associated with oxidative stress during
      pregnancy.
AB  - We sought to determine if maternal periodontal disease is associated with
      oxidative stress as measured by serum 8-isoprostane. A secondary analysis was
      conducted using prospective data from the Oral Conditions and Pregnancy Study.
      Healthy women enrolled at < 26 weeks' gestational age underwent oral examination
      and serum sampling. Maternal periodontal disease status was categorized as
      healthy, mild, or moderate to severe by clinical criteria. Maternal serum was
      analyzed for 8-isoprostane using ultrasensitive enzyme-linked immunosorbent
      assay. Elevated 8-isoprostane level was defined as >= 75th percentile. Maternal
      factors associated with elevated 8-isoprostane were determined using chi-square
      or T test. Multivariable logistic regression was used to assess association
      between elevated 8-isoprostane and maternal factors. Seven hundred ninety-one
      women had complete data. Median (interquartile) 8-isoprostane serum level was
      1806 (16 to 81,870) pg/dL. Using bivariate analysis, maternal age, race, marital
      status, utilization of public assistance, and mild or moderate to severe
      periodontal disease were associated with elevated serum 8-isoprostane. Using
      logistic regression, moderate to severe periodontal disease (adjusted odds ratio
      2.9, 95% confidence interval: 1.7 to 5.0) remained significantly associated with
      an elevated serum 8-isoprostane level. Maternal periodontal disease is associated
      with oxidative stress during pregnancy. Further study is needed to determine the
      role of maternal oxidative stress in periodontal disease-associated adverse
      pregnancy outcomes.

PMID- 21082539
TI  - Type and timing of ventilation in the first postnatal week is associated with
      bronchopulmonary dysplasia/death.
AB  - The type and timing of respiratory support in the first week affecting
      bronchopulmonary dysplasia (BPD)/death have not been evaluated. We compared
      outcomes of premature infants on nasal intermittent positive pressure ventilation
      (NIPPV) or nasal continuous positive airway pressure (NCPAP) to those on
      endotracheal tube (ETT). We retrospectively reviewed data (1/2004 to 6/2009) of
      infants <= 30 weeks' gestational age (GA) who received NIPPV in the first
      postnatal week. National Institutes of Health consensus definition was used for
      BPD. Infants were categorized into three groups based on their being on a
      particular respiratory support mode for majority of days in the first week. There
      was no difference in the mean GA and body weight in the three groups: ETT (N =
      65; 26.7 weeks; 909 g), NIPPV (N = 66; 27.1 weeks; 948 g), and NCPAP (N = 33;
      27.4 weeks; 976 g). Use of surfactant was significantly different. In
      multivariate analysis, compared with ETT, NIPPV (P < 0.02) and NCPAP (P < 0.01)
      groups were less likely to have BPD/death. Infants on ETT (N = 97) during 1 to 3
      days were more likely to have BPD/death compared with those on NIPPV (N = 38):
      67% versus 47% (P = 0.035). Infants on ETT (N = 30) during 4 to 7 days were more
      likely to have BPD/death compared with those extubated to NIPPV (N = 36): 87
      versus 53% (P = 0.003). Extubation to NIPPV or NCPAP in the first postnatal week
      is associated with decreased probability of BPD/death.

PMID- 21082540
TI  - Time and number of displays impact critical signal detection in fetal heart rate
      tracings.
AB  - Interest in centralized monitoring in labor and delivery units is growing because
      it affords the opportunity to monitor multiple patients simultaneously. However,
      a long history of research on sustained attention reveals these types of
      monitoring tasks can be problematic. The goal of the present experiment was to
      examine the ability of individuals to detect critical signals in fetal heart rate
      (FHR) tracings in one or more displays over an extended period of time. Seventy
      two participants monitored one, two, or four computer-simulated FHR tracings on a
      computer display for the appearance of late decelerations over a 48-minute vigil.
      Measures of subjective stress and workload were also obtained before and after
      the vigil. The results showed that detection accuracy decreased over time and
      also declined as the number of displays increased. The subjective reports
      indicated that participants found the task to be stressful and mentally
      demanding, effortful, and frustrating. The results suggest that centralized
      monitoring that allows many patients to be monitored simultaneously may impose a
      detrimental attentional burden on the observer. Furthermore, this seemingly
      benign task may impose an additional source of stress and mental workload above
      what is commonly found in labor and delivery units.

PMID- 21082541
TI  - Polyhydramnios with bidirectional fetal ductus arteriosus flow in a fetus with
      congenital diaphragmatic hernia: case report.
AB  - The etiology of polyhydramnios may be attributed to either increased production
      of amniotic fluid (fetal polyuria or high-output cardiac failure) or decreased
      fetal swallowing (obstruction or neurological impairment). Although idiopathic
      polyhydramnios occurs in nearly half of all cases, it is often associated with
      fetal abnormalities. Fetal ductus arteriosus flow is normally from right to left.
      We report a case of antenatally detected bidirectional fetal ductus arteriosus
      flow diagnosed concomitantly with polyhydramnios. Amnioreduction was performed
      due to severe maternal symptoms, which resulted in correction of the fetal ductus
      arteriosus flow. Postnatal diagnosis of a Morgagni diaphragmatic hernia indicates
      that our sonographic findings collectively may have been a diagnostic clue.

PMID- 21082542
TI  - [Canaloplasty and transient anterior chamber haemorrhage: a prognostic factor?].
AB  - OBJECTIVE: An attempt has been made to evaluate transient anterior chamber
      haemorrhage after canaloplasty. METHOD: In the period from November 2008 to
      October 2009 a total of 21 eyes in 17 patients underwent canaloplasty for primary
      open angle glaucoma in our clinic. At the end of surgery all eyes left the
      surgical table with an intraocular pressure (IOP) of 5 - 10 mmHg and a deep
      anterior chamber without any bleeding. RESULTS: The IOP on day 1 after surgery
      was 9.6 mmHg in average. By that time 15 of 21 eyes showed anterior chamber
      haemorrhage with a hyphaema between 0.5 - 2 mm in height. Eyes without hyphaema
      showed an IOP of > 15 mmHg at the same time. In no case was there further
      haemorrhage, the blood was absorbed in all cases within a maximum of 1 week
      without further complications. CONCLUSION: In contrast to trabeculectomy, where
      the natural anterior chamber water outflow is by-passed via an artificial
      fistula, canaloplasty attempts to re-establish the physiological anterior chamber
      water draining system by means of a 360 degree viscocanalostomy and a thread
      mediated dilation of Schlemm's canal and its collector channels. If the anterior
      chamber pressure temporarily lowers the level of the venous capillary pressure,
      it is consistent with a patent piping system when a reverse flow with blood
      reflux into the anterior chamber can be observed as long as a minimal
      physiological pressure gradient from the anterior chamber in the direction of
      channel Schlemm's canal has been restored. Thus, in the authors opinion, anterior
      chamber haemorrhage shows the desired consistency of the water draining system
      and should therefore logically be expected after each successful operation in all
      cases where hypotony in the postoperative period occurs.

PMID- 21082543
TI  - [New targets for blood pressure lowering in diabetic patients?].

PMID- 21082544
TI  - [Solitary hyperfunctioning thyroid gland carcinomas].
AB  - BACKGROUND: Thyroid gland carcinomas usually appear as afunctional and
      hypofunctional lesions on thyroid scintigrams, but some rare cases of thyroid
      carcinoma with scintigraphic hyperfunctional lesions have also been reported. The
      aim of our retrospective study was to elucidate the frequency of carcinomas in
      patients operated for solitary hyperfunctional thyroid nodules and to represent
      their demographic and clinical features. PATIENTS AND METHODS: During one decade
      (1997/2006), 308 patients were operated for solitary hyperfunctional thyroid
      nodules in the Centre for Endocrine Surgery in Belgrade. RESULTS: Malignancy was
      revealed in 9 cases (about 3 %) by histopathological examination. In 6 cases
      papillary microcarcinomas were found adjacent to dominant hyperfunctional
      adenomas, while in 3 cases (about 1 %) real hyperfunctional carcinomas were
      confirmed. Follicular carcinoma was diagnosed in 2 cases and papillary carcinoma
      in one. All 3 patients were preoperatively hyperthyroid. In both patients with
      follicular carcinoma we performed lobectomies. In the third case we carried out a
      total thyroidectomy considering the intraoperative frozen section finding of a
      papillary carcinoma. CONCLUSIONS: According to our results the frequency of
      solitary hyperfunctioning thyroid carcinomas is about 1 %, so that the
      possibility that a hyperfunctional nodule is malignant should be considered in
      the treatment of such lesions.

PMID- 21082545
TI  - Single-access laparoscopic surgery using new curved reusable instruments: initial
      hundred patients.
AB  - In recent years, laparoscopic surgery underwent a huge investment from both the
      clinical and research points of view to perform classic procedures through a
      single (S) incision or single port, resulting in the development of different
      instruments and ports. The main advantage of the S-access laparoscopy (SAL) is
      cosmesis. Future investigations will provide other potential advantages, such as
      improvement in postoperative pain and patient satisfaction. We report our initial
      experience on 115 patients utilizing a SAL (appendectomy, cholecystectomy,
      incisional hernia repair, Nissen fundoplication, upper gastrointestinal surgery,
      diagnostic laparoscopy, hepatic resection, splenectomy), along with the new
      curved reusable instruments (Karl Storz-Endoskope, Tuttlingen, Germany). The
      curves of the instruments enable the surgeon to work in an ergonomic position
      similar to classic laparoscopy, establishing a working triangulation inside the
      abdomen as well as outside. The cost of SAL is similar to classic laparoscopy as
      only reusable products are used.

PMID- 21082546
TI  - Digital video recordings for training, assessment, and revalidation of surgical
      skills.
AB  - Surgical training is undergoing drastic changes, and new strategies should be
      adopted to keep quality standards. The authors review and advocate the use of
      surgical recordings as a useful complement to current training, assessment, and
      revalidation modalities. For trainees, such recordings would promote quality
      based and competence-based surgical training and allow for self-evaluation. Video
      logbooks could be used to aid interaction between trainer and trainee, and
      facilitate formative assessment. Recordings of surgery could also be integrated
      into trainees' portfolios and regular assessments. Finally, such recordings could
      make surgeons' revalidation more sensible. The routine use of records of surgical
      procedures could become an integral component of the standard of care. This would
      have been an unattractive suggestion until recently, as analogue recording
      techniques are inconvenient, cumbersome, and time consuming. Today, however, with
      the advent of inexpensive digital technologies, such a concept is realistic and
      is likely to improve patient care.

PMID- 21082547
TI  - Reduced port surgery: an economical, ecological, educational, and efficient
      approach to development of single port access surgery.
AB  - There has been an emergence of reduced port techniques for laparoscopic surgery
      over the past three years. Although growing in presentations and papers, few
      scientific studies have yet to be published demonstrating benefits and risks of
      these techniques. In particular, very little is mentioned regarding the increased
      costs. This brings to the forefront the concept that the development of new
      surgical techniques should adhere to safe standards of surgery and undergo
      continued evaluation during development to ensure they maintain safety, and are
      able to be reproduced by our colleagues. Evaluation also needs to focus on costs,
      both economical and ecological. A review of our first three years experience of
      single port access surgery has been done. Costs in terms of both the potential
      economic and environmental impact have also been evaluated as compared with
      multiport procedures. In the first 36 months of this evolving technique, we were
      able to mimic multiport procedures with similar results. The costs of single port
      access are less than comparable multiport procedures, both in terms of dollars as
      well as medical waste. We are able to now offer "proof of concept" of a novel
      reduced port procedure from four important aspects in the development of new
      surgical techniques. We demonstrate comparable results in terms of outcomes and
      safety, improvement in financial and environmental costs, as well as showing
      initial success with training and application of the procedure by our colleagues.

PMID- 21082548
TI  - First Italian experience in single-incision laparoscopic nephrectomy.
AB  - We describe our laparoscopic nephrectomy technique of placing trocars directly on
      the fascia once the skin and the subcutaneous layers are prepared. A series of 10
      consecutive patients were operated on by single-incision laparoscopic nephrectomy
      (SILN). With a 5-cm mean skin incision, the fascia was prepared and 3/4 trocars
      inserted separately directly on the fascia. Surgical strategy followed the
      standard technique, except for the use of articulating instruments and 5-mm
      optic. Demographics, body mass index (BMI), operative time, blood loss,
      perioperative complications, transfusions, hemoglobin decrease, analgesic
      requirement, length of stay, and final pathology were recorded. Postoperative and
      prior-to-discharge visual analogue scale (VAS) pain evaluations were also
      collected, together with the limitations inherent in the instruments' placement
      and parallel driving during the procedure. The procedures were successfully
      completed in all but one case. The mean operative time was 169 min. (mean blood
      loss 113 ml). Without major perioperative complications, the patients were
      discharged early (mean 5.3 days). Four patients had a BMI>30. For specimen
      retrieval (neoplasms) two trocar holes were joined. One patient required
      analgesics; the mean post-operative and prior-to-discharge VAS scores were 5.7
      and 1.4, respectively. Pathology examination confirmed 4 pyelonephritic kidneys,
      4 renal carcinomas, and 2 upper-urinary tract carcinomas. The laparoscopic
      nephrectomy via a single incision is feasible and safe, with favorable
      perioperative and short-term outcomes. It's technically more challenging than
      standard laparoscopy requiring advanced surgical skills.

PMID- 21082549
TI  - SPIDER and flexible laparoscopy: the next frontier in abdominal surgery.
AB  - With the introduction of natural orifice translumenal endoscopic surgery (NOTES),
      there has been interest in the general surgery community for developing safe,
      scarless surgery. NOTES itself brought additional risks to GI surgery, and as
      such it has not achieved mainstream acceptance. Single site is considered by many
      surgeons as a bridge between traditional laparoscopic surgery and NOTES without
      the inherent risks of NOTES. However, initial single-site procedures using
      standard instrumentation are technically challenging due to the absence of
      instruments that facilitate triangulation, avoid conflicts between the
      instruments and the camera, maintain pneumoperitoneum, and reduce operative
      stress. The TransEnterix SPIDER platform has been created to overcome these
      difficulties. The SPIDER is a sterile and disposable device that contains 4
      working channels (2 flexible instrument delivery tubes positioned laterally and 2
      rigid channels, superiorly and inferiorly to accommodate an endoscope or any of
      the shelf rigid surgical instruments). Procedures facilitated by this platform
      are considered to use a hybrid flexible laparoscopic technique. Initial
      experience in over 100 cases with the SPIDER, including colectomy,
      cholecystectomy and adjustible gastric banding, has shown this system to be
      effective. Technical pearls when using the SPIDER include pulling rather than
      pushing, and increased use of electrocautery. These learning curve lessons for
      flexible laparoscopy will be described in detail, including a discussion of
      advantages and disadvantages. The SPIDER platform facilitates safe and
      straightforward single-site laparoscopic surgery.

PMID- 21082550
TI  - Innovation and management of diabetic foot wounds.
AB  - Recent innovations in the field of wound healing have created numerous advanced
      therapies from which clinicians may now choose. The challenge for the
      reconstructive surgeon is to ensure that these adjunct technologies are used
      according to an evidence-based protocol to ensure optimal healing. Critical to
      successful outcomes is that new modes of therapy do not supplant, but are used in
      tandem with, core principles of wound management: establishing a correct
      diagnosis, ensuring a good local blood supply, debriding the wound to a clean
      base, correcting the biomechanical abnormality, and nurturing the wound until it
      shows signs of healing. Debridement should be performed as often as necessary
      until the wound is deemed clean and ready for reconstruction. Useful adjuncts in
      debridement include hydrotherapy and ultrasonic therapy. The majority of
      reconstructions are accomplished through simple techniques. If a wound is not
      meeting the expected healing trajectory, management adjuncts such as negative
      pressure wound therapy, growth factor, cultured skin, and hyperbaric oxygen can
      then reactivate or expedite the process toward achieving a healed wound.

PMID- 21082551
TI  - The use of antimicrobial dressings in chronic wounds: NERDS and STONEES
      principles.
AB  - Wound infection is common and delays wound healing. Validated signs included in
      the mnemonic NERDS and STONEES can be used to identify whether bacterial damage
      is superficial or deep, respectively. Clinicians must discern when bacterial
      damage has occurred on a timely basis and what treatment strategies to institute.
      A variety of topical antimicrobial agents have been developed incorporating
      iodine, chlorhexidine, silver, honey, topical oxygen, and topical antibiotics.
      Selection of appropriate strategies should be based on three key factors:
      healability (healable versus nonhealable), bacterial burden (colonization versus
      deep infection), and host risk factors. This article reviews and offers succinct
      recommendations pertaining to the management of wound infection in clinical
      practice.

PMID- 21082552
TI  - New therapies for treatment of diabetic foot ulcers: a review of current clinical
      trials.
AB  - Diabetic foot ulcers are a common problem in clinical practice and one of the
      most common complications in diabetic patients, often leading to amputation and
      hospitalization. Although there are a number of options for coadjuvant therapy
      for diabetic foot ulcers, a considerable number of patients remain unhealed after
      12 weeks of treatment and, in general, rates of healing remain low. For these
      reasons, as well as the rising costs of associated complications of nonhealing
      diabetic foot ulcers, there is an impetus for the research community to develop
      more sophisticated ways to manage this condition. We reviewed ongoing clinical
      trials (clinicaltrials.gov) testing new therapies for foot ulcers and searched
      the basic science literature for preclinical background of these products. We
      focused our review on new therapies that include topicals, skin substitutes,
      bioengineered skin, cellular therapy growth factors, devices, and herbal
      medications. All of these options are analyzed and presented in this review as
      promising new options for the treatment of diabetic foot ulcers.

PMID- 21082553
TI  - Diabetic foot ulcers: current treatment options and new developments.
AB  - Diabetic foot ulcers are a marker of far more serious underlying co-morbidities
      that often represent a precursor to infection, amputation, and death. The
      treatment of diabetic foot ulcers is marked by many options that represent both
      potential opportunity and hindrance. Thousands of products are available to the
      provider, yet confusion often exists as to the indications, as well as when and
      how to use such modalities. Increased availability of treatment modalities can be
      overwhelming to providers, and as such, can lead to reliance on outdated and
      unproven methods. Current diabetic foot ulcer treatment options are often based
      on clinical and anecdotal findings. Evidencebased treatment options are limited.
      An overview of diabetic foot ulcer management is presented in an organized manner
      to assist providers in their decision making in treating diabetic foot ulcers,
      with a goal of improving clinical outcomes and reducing amputations.

PMID- 21082554
TI  - Needlescopic cholecystectomy.
AB  - Minimally invasive techniques have revolutionized the art of surgical practice.
      The laparoscopic approach to cholecystectomy has become the gold standard and is
      the most common laparoscopic general surgery procedure worldwide. In an effort to
      further enhance the advantages of laparoscopic surgery even less-invasive methods
      have been attempted, including smaller and fewer incisions. The objective of this
      study was to describe our results with over 15 years of needlescopic
      cholecystectomies. At the Texas Endosurgery Institute, 434 operations were done
      by a single surgeon from 1995 to 2010. Eighty-six percent of subjects were
      female, and the average age of all subjects was 41.9 years (range 14-82). The
      average operating time was 59.3 minutes (range 30-200). The 200-minute operation
      required laparoscopic CBD exploration, accounting for the extended time. Average
      estimated intraoperative blood loss (EBL) was <15 cc (range 0-50 cc). Two percent
      of cases required conversion to standard 5-mm cholecystectomy and were completed
      without incident. All patients are followed up at two weeks and then at six
      months. Since 1995, only one patient presented with a hernia at the umbilical
      site. Otherwise, no wound, bile duct, bile leak, bleeding, or thermal injury
      complications have been identified.

PMID- 21082555
TI  - Water-jet dissection in rectal cancer surgery: surgical and oncological outcomes.
AB  - These days the treatment of rectal cancer remains an encounter for various
      medical disciplines. A key position in the whole concept of therapy is still
      taken by surgery itself. To facilitate the advantages of the total mesorectal
      excision (TME) we used the water-jet dissector (WJD) in our surgical routine. Our
      object was to analyze perioperative data as well as oncological long-term results
      following WJD-assisted rectal resection. MATERIALS AND METHODS: A total of 226
      patients underwent surgery for rectal cancer in our center between October 2001
      and June 2009. A retrospective review was performed of all WJD-assisted rectal
      resections during this time. One hundred and five patients with adenocarcinoma of
      the lower and middle rectum were operated on by 7 surgeons according to the
      concept of TME. Seventy-six patients underwent a low anterior resection, 29
      patients an abdominoperineal resection. Twenty-eight patients received
      preoperative radiochemotherapy. The median follow-up period amounted to 35 (2-96)
      months. Survival rates were calculated using the Kaplan-Meier method. RESULTS:
      Anastomotic leakage occurred in 5.7%, wound healing disturbance (including
      perineal wound infections) in 29.5%, intra-abdominal infections in 7.6% and
      urinary tract infections in 7.6%. Postoperative bladder dysfunction (requiring
      catheterization) occurred in 1.9%. Postoperative 30-day mortality was 0%, 60-day
      mortality 1%. The rate of local recurrence (including three patients who refused
      postoperative radiochemotherapy) was 8.5%. Cancer-specific survival at 5 years
      was 74% and differed significantly by stage. CONCLUSIONS: The particular advance
      of the WJD is the facile development of the embryological plane between the
      mesorectal fascia and the surrounding pelvic nerves. Without harming one of them,
      maximum radicality and excellent autonomic nerve preservation can be achieved.
      The WJD is a technique with acceptable postoperative morbidity and low mortality.
      Local control and survival are comparable to other surgical centers in
      international literature.

PMID- 21082556
TI  - Anatomic relation between the umbilicus, aortic bifurcation, and transverse colon
      in males.
AB  - To examine the relationship between the umbilicus, major abdominal vessels, and
      transverse colon in males with differing body habitus, we conducted a prospective
      study including 91 male patients who underwent computerized tomography scan
      examinations. Of 91 males, 40 were normal weight, 27 overweight, and 24 obese.
      Compared with males of normal weight, the distance between the umbilicus and
      peritoneum was significantly greater in those who were overweight and obese. In
      males in whom the umbilicus was located cephalad to the aortic bifurcation, the
      distance was 1.4 to 2 cm. There was no significant difference in the distance
      among those who were normal weight, overweight, or obese. In males whose
      umbilicus was caudal to the aortic bifurcation, the distance in obese males
      (2.3+/-0.3 cm) was significantly greater than in those with normal weight (1.2+/
      0.2 cm; P<0.01). Compared with normal weight males (8.6+/-0.7 cm), the distance
      between the umbilicus and transverse colon was significantly greater in the
      overweight males (10.7+/-0.7 cm, P: 0.02 CI -0.3 to -4.2) and obese males (11.5+/
      1.0 cm, P: 0.01; CI-0.4 to -5.0). The location of the aortic bifurcation in
      relation to the umbilicus in men varies. However, generally the umbilicus is
      located caudal to the transverse colon.

PMID- 21082557
TI  - End-type stapled colostomy in emergency surgery.
AB  - INTRODUCTION: Colostomy is one of the most frequent procedures in emergency
      surgery. Several techniques have been described. The aim of this essay is to
      present our results using a circular stapler device when executing an end-type
      colostomy raising in emergency surgery. MATERIAL AND METHODS: During a period of
      4 years, 47 patients underwent end-type colostomy raised under emergency
      circumstances using a circular stapler device. We gathered information on each
      patient, and performed 2 years follow-up. RESULTS: Forty-seven patients, 72.3%
      male and 27.7% female, were enrolled in this study. The most common indication
      was colorectal cancer (48.9%). We had an average rate of complications of 13.63%
      without a need to be operated on: parastomal hernia (6.81%), mild local
      cellulitis (4.54%), and retraction (2.27%). The medium diameter of colostomy at
      the time of surgery and after 1 month was equal to 3.4 cm and 3.1 cm
      respectively. Follow-up screenings showed that the diameter of colostomy held
      constant at 3 cm. DISCUSSION: End-type colostomy using a stapler device can be
      safely performed under emergency circumstances. It is not related to a higher
      rate of stomal stenosis in our series. This is the first essay that reports the
      diameter of colostomy with this technique. Early and late complications are
      similar to those that appear with the classical technique. Therefore, the end
      type colostomy executed by means of a circular stapler device can be considered a
      safe and reliable technique.

PMID- 21082558
TI  - Case report: laparoendoscopic single-site fenestration of giant hepatic cyst.
AB  - Laparoendoscopic single-site (LESS) surgery has developed as a new surgical
      modality producing increased cosmetic benefits over conventional endoscopic
      surgery. However, there are limited reports about LESS surgery in liver diseases.
      We reported a case of a giant hapatic cyst that was treated by LESS surgery. LESS
      fenestration was performed on a 60-year-old female. A 2.2-cm umbilical incision
      was made. Three laparoscopic trocars were individually inserted into the
      abdominal cavity via a single umbilical incision. Only straight laparoscopic
      instruments were applied throughout the procedures. Aspiration, dome resection,
      argon laser coagulation, drainage, and removal were performed by LESS surgery.
      One of the 5-mm trocars was replaced with a 12-mm trocar to retrieve the resected
      cyst wall. All of the procedures for liver fenestration were the same as
      conventional laparoscopy and were successfully performed without any
      difficulties. The patient had an uncomplicated postoperative course. The LESS
      surgery has been successfully applied to liver fenestration as an available
      alternative to conventional laparoscopic fenestration. This method is technically
      feasible and results in superior cosmesis.

PMID- 21082559
TI  - Current status of laparoscopic bariatric surgery.
AB  - As the prevalence of obesity has dramatically increased and obesity has become
      one of the leading public health threats worldwide, the number of bariatric
      surgeries performed has been exponentially increasing. According to a recent
      survey, over 90% of bariatric procedures are performed by laparoscopic approach.
      The most commonly performed procedures are Roux-en-Y gastric bypass (open and
      laparoscopic), followed by laparoscopic adjustable gastric banding, and sleeve
      gastrectomy. Definite geographic trends are observable in the specific bariatric
      procedures being performed. A number of studies have already demonstrated the
      efficacy of bariatric surgery for the treatment of obesity and its comorbidities,
      although there are still only a handful of prospective, controlled studies with a
      high level of evidence. Considering the results derived from a large-scale,
      prospective, multicenter study and a systematic review, it can be reasonably said
      that bariatric surgery is a safe and feasible intervention for the treatment of
      life-threatening morbid obesity under controlled conditions. So far, several
      studies have shown improved survival rates for patients who undergo bariatric
      surgery compared with a control cohort of severely obese patients who did not. In
      addition, bariatric surgery seems to have a positive impact on the economy,
      although currently only about 1-2% of eligible patients with morbid obesity
      receive bariatric surgery. In this mini-review article, we summarize bariatric
      surgery outcomes by quoting some of the recently published landmark articles.

PMID- 21082560
TI  - Laparoscopic jejunal sleeve: a simple and ideal new technique for revision of
      Roux-en-Y gastric bypass after weight regains technical aspects.
AB  - Revision of gastric bypasses that fail is one of the most difficult challenges
      that face bariatric surgeons these days. Adding a foreign body like a band or a
      silastic may give unsatisfactory results, while increasing malabsorption may
      result in severe malnutrition and hypoproteinemia. Laparoscopic jejunal sleeve is
      based on the principles of laparoscopic sleeve gastrectomy applied to a failed
      Roux-en-Y gastric bypass. The procedure is simple and involves only stapling, is
      reproducible, accessible, effective, and safe, without foreign bodies. Weight
      loss may be achieved to give an extra 5 to 10 points of BMI reduction. Early
      complications are similar to laparoscopic sleeve gastrectomy and may involve
      leaks and strictures. Mid- and long-term weight loss data are lacking at the
      present time, and patients should be selected based on an initial response to
      their gastric bypass.

PMID- 21082561
TI  - Current status of laparoscopic gastrectomy for gastric malignancies.
AB  - Minimally invasive surgery for gastric cancer has been an important treatment
      modality since its introduction in 1991 from Japan. The practice of surgical
      techniques in laparoscopic gastrectomy with lymph node dissection is improving
      and evolving. Furthermore, advanced techniques including total gastrectomy,
      proximal gastrectomy, extended lymph node dissection and robot-assisted
      gastrectomy, have been safely carried out. A retrospective multicenter study in
      Japan has shown that the short-term outcomes of laparoscopic gastrectomy are
      beneficial, and the long-term outcomes are the same as those for open surgery.
      Recently, prospective multicenter randomized controlled trials have been
      conducted in Japan and Korea to evaluate the safety and oncological feasibility
      of laparoscopic gastrectomy for clinical stage I gastric cancer or advanced
      gastric cancer. In the future, laparoscopic surgeons will need to design and
      implement education and training systems for standard laparoscopic procedures
      based on the clinical outcomes of multicenter randomized controlled trials.

PMID- 21082562
TI  - Laparoscopic gastric banding and individual bariatric surgery.
AB  - Different factors (strategic, anatomical, instrumental, etc.) can cause difficult
      surgical situations, especially in bariatric surgery. In a difficult surgical
      situation, the surgeon faces a dilemma as to whether to continue the intended
      operation "at all costs" or to deviate from the initially planned surgical
      procedure to some alternative technique or procedure. The dilemmatic nature of
      the difficult surgical situation in bariatric surgery has motivated us to discuss
      the following aspects because they all contribute to the problem: standards in
      bariatric surgery, deviation from standards, the role of experts, and the focus
      of research. We also propose to classify bariatric patients according to
      intraoperative difficulty (I to IV) as: (I) ideal cases (i.e., easy to operate,
      no problems), (II) not quite ideal cases (some minor difficulties may occur),
      (III) problematic cases (difficult to operate, some operative techniques are
      considerably more difficult than others), and (IV) very difficult cases (every
      operative step is difficult). We discuss the establishment of a registry of
      difficult surgical situations including the possibilities of deviating from the
      standard. Scientific analyses of such registries should focus on patients with
      apparent modifications in treatment (process deviations), but might also look at
      those with surprisingly good or bad results (outcome deviations). The technical
      steps of laparoscopic adjustable gastric banding (LAGB) have been chosen to
      illustrate this concept.

PMID- 21082563
TI  - Routine hiatal hernia repair in laparoscopic gastric banding.
AB  - Laparoscopic gastric banding is now well established as an effective means of
      obtaining safe, healthy weight loss in the morbidly obese patient population. The
      procedure has evolved over the years to minimize complications and optimize
      results. Preoperative patient evaluation includes upper endoscopy to assess the
      baseline integrity of the stomach and rule out pathology. Upper endoscopy fails
      to demonstrate the majority of small hiatal hernias in these patients
      preoperatively. Hiatal hernias are grossly underappreciated in patients with
      morbid obesity due to the presence of a large distal esophageal fat pad. With
      post-operative internal weight loss, a small crural defect can become relatively
      large in a short amount of time. Performing gastric banding without dissecting
      and repairing the hiatal hernia can lead to incorrect positioning of the gastric
      band, which is associated with poor weight loss, chronic reflux, and increased
      complications. Concomitant hiatal hernia repair is felt by the authors to be a
      necessary component for the correct placement of the gastric band device, which,
      in turn, provides excellent long-term results to our patients.

PMID- 21082564
TI  - Preoperative prediction of stomach weight to be removed in laparoscopic sleeve
      gastrectomy procedure.
AB  - Sleeve gastrectomy (SG) is a surgical procedure that includes a longitudinal
      lateral gastrectomy to reduce food intake by reducing the capacity of the
      stomach. The technique of SG as a primary procedure has evolved since it was
      first introduced in 2001. Some perform the SG over smaller bougie sizes (30-40
      Fr) or an NG tube. Some begin the SG near the pylorus (2 cm) while others avoid
      the antral/pyloric area. Establishing the mass or volume of stomach remaining is
      subject to limitations associated with the in vivo status. However, quantifying
      the amount (mass) of stomach removed is definitively an objective measure. The
      study was conducted to determine the relationship between the amount of stomach
      excised and the patient's gender and preoperative weight and height. Data was
      collected prospectively and was compiled in a review of 165 (136 Female and 29
      Male) patients who underwent laparoscopic SG from December 7, 2001 to March 18,
      2004 by a single surgeon at three institutions using the same technique for
      performance and measurement. The empty weight and capacity of resected stomach
      specimens were measured intra-operatively and subsequently correlated with the
      patient's gender, preoperative weight, and height. The mean height of male
      patients was 179.7+/-7.1 (CM) and the mean height of female patients was 165.1+/
      7.1(CM). The mean weight of stomach tissue removed from male patients was 160.3+/
      29.4 (G) and from female patients was 123.5+/-40.4 (G). The difference in height
      and weight between men and women was statistically significant (P-value<0.0001).
      The empty stomach weight and capacity both are linearly related to each other (R
      square=0.9292, P-value<.0001). There is evidence showing the statistically
      significant correlation among preoperative height, gender, and preoperative
      weight and amount of stomach removed. For the average height patient, removal of
      gastric tissue weighing less than 160 grams in males and 120 grams in females may
      indicate an inadequate resection. This removes a stomach capacity of
      approximately 1600 cc's and 1200 cc's respectively.

PMID- 21082565
TI  - Current developments in hernia repair; meshes, adhesives, and tacking.
AB  - Open and laparoscopic hernia surgery continues to evolve with new products
      allowing surgeons multiple choices in treating their patients. The evolution
      towards tension-free techniques in dealing with hernias requires that today's
      surgeons know the options available in meshes as well as fixation methods in
      order to have the best outcomes. In recent years, there has been a rapid
      expansion in the number of meshes available. Currently, there are numerous
      uncoated, coated, and biologic meshes in production that can be used in hernia
      repair. This paper will focus on the latest developments in coated meshes that
      allow for intra-abdominal placement as well as the different types of biologic
      meshes and their typical uses. Tacking devices for laparoscopic hernia repair now
      come in titanium as well as absorbable devices. AbsorbaTackTM (Covidien, Norwalk,
      CT) and SorbafixTM (Davol, Warwick, RI) are two of the newest absorbable tacking
      devices thought to possibly benefit patients with decreased pain and long-term
      complications as compared with their titanium counterparts. Adhesives continue to
      be used more and more for hernia repair, especially in inguinal and
      paraesophageal hernia repairs. TissucolTM/TisseelTM (Baxter, Deerfield, IL) and
      EvicelTM (Ethicon, Somerville, NJ) are two types of fibrin glues that are
      available for use in hernia repair. Practitioners using these biologic adhesives
      think there is less pain compared with tacking.

PMID- 21082566
TI  - A new technique for minimally invasive abdominal wall reconstruction of complex
      incisional hernias: totally laparoscopic component separation and incisional
      hernia repair.
AB  - Since Ramirez et al. presented the first case of component separation for
      abdominal wall hernias in 1990, it has undergone multiple modifications. This
      technique, which has been mainly used for large hernias where primary closure of
      the abdominal wall is not feasible, or for staged management of patients with
      open abdomens, results in multiple wound complications. In 2007, Rosen et al.
      reported on the laparoscopic approach to component separation that is associated
      with less subcutaneous dissection and the consequent advantage of a decreased
      risk of flap necrosis and wound infection. Here we discuss our totally
      laparoscopic approach to abdominal wall reconstruction. A minimally invasive
      abdominal wall reconstruction consists of a bilateral component separation, an
      intra-abdominal adhesiolysis, primary approximation of rectus muscles, and
      placement of an intraperitoneal mesh for reinforcing the repair, all performed
      laparoscopically. Patient-selection criteria, detailed operative technique, tips
      in preventing and managing the potential pitfalls, and postoperative care are
      discussed.

PMID- 21082567
TI  - Laparo-endoscopic single site hysterectomy in gynecologic surgery.
AB  - Laparo-endoscopic single site (LESS) surgery has recently gained broader
      acceptance as a less-invasive approach to traditional multi-port laparoscopic
      procedures. LESS hysterectomy represents the gynecologic surgeon's progression
      toward this goal of performing minimally invasive hysterectomy procedures through
      increasingly fewer incisions. Although this procedure offers improved cosmesis
      and potentially decreased post-operative pain, there are also many challenges to
      adoption of this surgical procedure. LESS hysterectomy is associated with a steep
      learning curve and the need for the gynecologic surgeon to adopt new technologies
      and develop a new set of surgical skills. Following the basic principles of LESS
      surgery is essential for the gynecologic surgeon to safely and efficiently adopt
      this surgical procedure. Advances in surgical instrumentation will continue to
      allow surgeons to perform increasingly complex LESS surgical procedures in the
      future.

PMID- 21082568
TI  - Global endometrial ablation.
AB  - Abnormal uterine bleeding (AUB) is a significant health problem for many women.
      Surgical treatment of AUB often follows failed attempts with first-line medical
      therapy. Hysterectomy, while being a definitive treatment, is a major surgical
      procedure with potential for significant complications and economic costs.
      Endometrial ablation was developed as an alternative to hysterectomy. The first
      generation endometrial ablation devices required extensive training and
      experience to be performed effectively and safely. As a result, newer ablative
      devices were developed addressing the need for less technical knowledge and
      improved safety. Since 1997, the United States FDA has approved 5 global
      endometrial ablation devices for treatment of AUB attributable to benign causes.
      This review will focus on the technical aspects of these second- generation
      devices and their applications for treatment of AUB.

PMID- 21082569
TI  - Advanced uterine manipulation technologies.
AB  - As the number of conventional laparoscopic and robot-assisted gynecologic
      surgeries continues to rise, efficient and safe uterine manipulation has become
      increasingly important. Currently described uterine manipulation techniques
      require constant manual manipulation by the surgeon or surgical assistant. This
      often necessitates extra operating room personnel, increases fatigue levels, and
      decreases efficiency. There are two new uterine manipulation devices that can
      improve these measures: the Uterine Positioning System(r) (UPS) (Cooper Surgical,
      Trumbull, CT) and the ViKY UP(r) "Vision Control for endoscopY" Uterine
      Positioner (EndoControl Medical, La Tronche, France). Both provide accurate and
      secure uterine positioning. The UPS can manipulate the uterus with minimal
      bedside involvement from the surgical team while the ViKY UP provides uterine
      manipulation through a robotic arm controlled by the surgeon remotely. These two
      devices can facilitate a multitude of conventional laparoscopic and robot
      assisted gynecologic surgeries.

PMID- 21082570
TI  - Suture management technique for tubotubo anastomosis of the fallopian tube.
AB  - The modified suspension technique for reanastomosis of the fallopian tube enables
      safer and more accurate placement of sutures at the anastomotic site. For all of
      the primary sutures, this technique enables careful inspection of the tissue
      layers prior to final approximation of the two tubal segments, thereby
      significantly reducing the possibilities of technical errors, such as posterior
      wall inclusion. This approach does not require the use of approximating clamps,
      and is an organized, well-staged approach.

PMID- 21082571
TI  - Clermont Ferrand uterine manipulator.
AB  - Laparoscopy was considered marginal to surgical specialties before 1990. Rare
      innovations in instruments were done. With the realization of the first
      laparoscopic hysterectomy, this surgical route gained wide acceptance during the
      1990s. Technical advances were made by instrument companies offering a wide
      variety of instruments to surgeons and by surgeons themselves to cope with
      problems during laparoscopic procedures. Manipulators are among the first
      instruments that surgeons suggested to ameliorate laparoscopic performance.
      Instruments that have multiple functions (i.e., grasping, cutting, coagulating)
      are more and more appreciated because surgeons can avoid changing instruments
      during surgery. Manipulators offer multifunctional assistance during gynecologic
      surgical procedures. They are useful for exposure purposes and also for
      reproductive surgery (and hysterectomy). This article explains the benefits and
      help that a manipulator can provide, especially in total laparoscopic
      hysterectomy. In the latter intervention, the manipulator will help to expose the
      pelvis by moving the uterus in any direction, to identify structures and find
      anatomical landmarks such as the vaginal fornices for culdotomy, and to avoid
      complications by pulling the ureter away from the operative field. Also, it is
      useful to avoid carbon dioxide leakage at the vaginal opening and to retrieve the
      surgical specimen. Each step is shown in a photograph with the specific hand
      movements corresponding to the manipulator's handling. We think that the use of
      manipulators during laparoscopic surgery is very useful and helps to reduce
      operative time.

PMID- 21082572
TI  - Robot-assisted laparoscopic colposacropexy and cervicosacropexy with the da
      Vinci(r) surgical system.
AB  - Colposacropexy is the gold standard operation for repair of apical vaginal
      support defects. Although it is feasible to perform this operation using
      conventional laparoscopic techniques, a limited number of surgeons have mastered
      the advanced minimally invasive skills that are required. Introduction of the da
      Vinci(r) robotic system (Intuitive Surgical, Sunnyvale, CA) with instruments that
      have improved dexterity and precision and a camera system with three-dimensional
      imaging presents an opportunity for more surgeons treating women with pelvic
      organ prolapse to perform the procedure laparoscopically. This chapter outlines a
      technique that is exactly modeled after the open procedure for completion of a
      robotic-assisted colpo- and cervicosacropexy using the da Vinci(r) surgical
      system.

PMID- 21082573
TI  - Laparoendoscopic single-site (LESS) adrenalectomy and partial nephrectomy:
      current Italian experience with two challenging surgical procedures.
AB  - Since its initial clinical use in urology, there has been an increasing
      enthusiasm and a growing interest for laparoendoscopic single-site surgery
      (LESS). Several clinical series have been reported with an estimated cumulative
      clinical experience of more than four hundred so far. Nowadays, virtually all
      extirpative and reconstructive urological procedures have been described and
      shown to be feasible and safe, including advanced reconstructive procedures and
      major extirpative ones. Among them, adrenalectomy and partial nephrectomy
      represent highly complex procedures. Initial clinical data have been recently
      reported to test the safety and efficacy of these interventions in selected
      patients. Herein, we describe our initial cases of unclamp LESS partial
      nephrectomy and adrenalectomy. In our opinion, LESS is an established technique
      within the field of minimally invasive surgery. Even if further studies are
      needed to demonstrate its actual benefits, early clinical outcomes are
      encouraging and LESS might represent the way to go in minimally invasive
      urological surgery.

PMID- 21082574
TI  - Orthotopic ileal bladder substitution following radical cystectomy using the
      linear-cutter stapling device.
AB  - We evaluated the safety, efficacy, and potential benefits of using the linear
      cutter staplers in the ileal reanastomosis and ileal pouch reconstruction
      following radical cystectomy in patients with invasive carcinoma of the urinary
      bladder. Radical cystectomy and orthotopic ileal bladder substitution procedures
      were performed in 40 patients with invasive carcinoma of the urinary bladder. In
      20 patients the linear- cutter stapling device was used for the ileo-ilial
      reanastomosis and reconstruction of the pouch, while in the other 20 patients the
      standard hand-suturing technique was used. Using the linear-cutter stapler in the
      ileo-ileal reanastromasis and ileal pouch reconstruction saved approximately 60
      to 90 minutes of operative time, and there was also a significant reduction of
      blood loss during this period. The leakage rate and hospital stay were less in
      patients with a stapled pouch. Urodynamic characteristics were comparable to
      standard ileal neobladders.

PMID- 21082575
TI  - Update on technologies for cardiac valvular replacement, transcatheter
      innovations, and reconstructive surgery.
AB  - Since the 2006 Surgical Technology International monograph on valvular
      prostheses, there have been significant developmental and investigative advances,
      particularly for transcatheter implantation. Aortic bioprostheses and mechanical
      prostheses continue to incorporate design changes to optimize hemodynamics and
      prevent prosthesis-patient mismatch and to have a potential satisfactory
      influence on survival. There have been continual technological improvements
      striving to bring forward advances that improve the durability of bioprostheses
      and reduce the thrombogenicity of mechanical prostheses. There also has been a
      continuance to preserve biological tissue with glutaraldehyde, rather than
      clinically evaluate other cross-linking technologies, by controlling or retarding
      calcification with therapies to control phospholipids and residual aldehydes. The
      techniques of mitral valve reconstruction have now been well established, and
      annuloplasty rings have been designed for the potential of maintaining the
      anatomical and physiological characteristics of the mitral annulus. There has
      been limited advancement in the past four years for interventional annuloplasty,
      for remodeling of the length and shape of the dilated annulus, prevention of
      dilatation of the annulus, and support for the potentially fragile area after
      partial-leaflet resection. Currently, there continues to be emergence of catheter
      based therapies, particularly for management of aortic stenosis but not mitral
      regurgitation. For management of selected populations with critical aortic
      stenosis, the techniques for aortic valve substitution have had further
      advancement for retrograde catheter techniques, as well as apical
      transventricular implantation. There has not been significant advancement during
      the past four years to address mitral regurgitation by experimental transcoronary
      sinus, stent-like devices and transventricular, edge-to-edge leaflet devices. The
      devices, descriptions, and pictorial images comprising this monograph have been
      limited to technologies that are considered to be predominant, at least for the
      immediate duration. The general purpose of the monograph is to serve as an
      educational document.

PMID- 21082576
TI  - Carotid endarterectomy: current consensus and controversies.
AB  - Stroke is the third most common cause of mortality, and carotid artery stenosis
      causes 8% to 29% of all ischemic strokes. Best medical treatment forms the basis
      of carotid stenosis treatment, and carotid endarterectomy (CEA) has an additional
      beneficial effect in high-grade stenosis. Carotid angioplasty and stenting (CAS)
      has challenged CEA as a primary carotid intervention. At present, CEA remains the
      gold standard, but in the future, CAS techniques will evolve and might become
      beneficial for subgroups of patients with carotid stenosis. This chapter briefly
      describes the history of carotid interventions and current consensus and
      controversies in CEA. In the last two years, several meta-analyses were published
      on a variety of aspects of best medical treatment, CEA, and CAS. It is still a
      matter of debate as to whether asymptomatic patients with carotid stenosis should
      undergo a carotid intervention. Especially because medical treatment has
      dramatically evolved since the early carotid trials. On the other hand, it is
      clear that carotid interventions in symptomatic patients with a high-grade
      stenosis should be performed as early as possible after the initial neurological
      event in order to achieve optimal stroke risk reduction. In CEA, the use of
      patching is advocated above primary closure, while the role of selective patching
      is still unclear. No differences in stroke and mortality rates are observed for
      routine versus selective shunting, for conventional versus eversion CEA, or for
      local versus general anesthesia. It is anticipated that in the future, there will
      be several interesting developments in carotid interventions such as plaque
      morphology analysis, acute interventions during stroke in progress, and further
      evolvement of CAS techniques.

PMID- 21082577
TI  - Update on endovascular management of infrarenal abdominal aortic aneurysms in
      2010; what has come and gone.
AB  - The past few decades have seen a very rapid change in the manner in which
      infrarenal aortic disease is diagnosed and dealt with. The approach has changed
      from open, large incision surgery with long and complicated postoperative courses
      to minimally invasive techniques in which the patient can go home the next day. A
      large number of devices have come and gone, and techniques to deal with aortic
      problems are ever changing. We have reviewed the past, current, and future
      technology to help make the treatment options more clear.

PMID- 21082578
TI  - Metal-on-metal bearings: the problem is edge-loading wear.
AB  - Metal-on-metal bearings are promoted as a low wear bearing alternative to
      traditional hip replacement bearings. While most in vitro studies support this,
      recent clinical reviews have found a significant number of early revisions in
      some designs of metal-on-metal bearings related to wear. Metal-on-metal bearings
      exhibit a bi-phasic wear pattern with high initial wear that generally settles
      down to low steady state wear. Previous publications from the authors have found
      that steady state wear occurs due to the formation of a critical conforming
      contact area. This contact area was found to be surprisingly constant regardless
      of bearing size, clearance, or even contact mode. The authors hypothesized that
      steady state wear may never be reached if formation of this critical conforming
      contact area is disrupted. Several hip simulator tests were performed to assess
      the wear performance of generic metal-on-metal samples at various angles of
      inclination. Three-dimensional modeling was performed on the generic bearing
      design as well as typical resurfacing and hemispherical bearing designs including
      various sizes and clearance ranges. Simulator results support the hypotheses, and
      wear rates were linear or accelerating when the critical contact area size could
      not be achieved due to its proximity to the rim of the bearing. Modeling studies
      show a correlation between bearing size and design and the maximum inclination
      angle allowed to reach steady state conditions. Smaller bearing size and
      shallower cup designs were found to reduce the maximum safe inclination angle and
      this corresponds to clinical observation of increased failure rates in these
      bearings. This simple method for assessing runaway wear risk can be utilized in
      the design of more robust and forgiving metal-on-metal bearings.

PMID- 21082579
TI  - Neck-modular femoral stems for total hip arthroplasty.
AB  - Modular total hip arthroplasty (THA) components have evolved significantly as the
      success of uncemented femoral fixation has been proven. Current trends in the
      United States include widespread use of cementless components (acetabular and
      femoral), usually with monoblock femoral stems with modular heads. Femoral offset
      has been proven to play a vital role in hip abductor strength, hip range of
      motion, and hip stability. Also critical to hip stability is the orientation of
      the acetabular and femoral components. Thus, offset and component positioning are
      fundamental to success in THA. Modularity of the femoral neck has been proposed
      to aid in further customizing the THA component fit. Neck-modular stems enable
      the adjustment of leg length, femoral anteversion, and femoral offset
      independently of stem size. Modularity of the neck allows the surgeon to
      precisely match the anatomic characteristics of each patient to yield improved
      range of motion, stability, abductor strength, and leg length equality.
      Disadvantages are related to cost and the addition of another interface. Neck
      modular femoral stems are not a new concept; however, as tough component
      manufacturing has advanced, these stems have been reintroduced to the
      armamentarium of the hip surgeon.

PMID- 21082580
TI  - The use of cementless acetabular component in revision surgery without pelvic
      discontinuity.
AB  - Reconstruction of the failed acetabular component in total hip arthroplasty (THA)
      can be challenging. Although there are multiple reconstructive options available,
      a cementless acetabular component inserted with screws has been shown to have
      good intermediate-term results and is the reconstructive method of choice for the
      majority of acetabular revisions This reconstruction is feasible provided at
      least 50% of the implant contacts host bone. When such contact is not possible,
      and there is adequate medial and peripheral bone, techniques using alternative
      uncemented implants can be used for acetabular reconstruction. An uncemented cup
      can be placed at a "high hip center." Alternatively, the acetabular cavity can be
      progressively reamed to accommodate extra-large cups. Oblong cups, which take
      advantage of the oval-shaped cavity resulting from many failed acetabular
      components, can also be used. The success of these cementless techniques depends
      on the degree and location of bone loss. The correct indication to revision and
      the choice of the correct implant is the keystone for the success of this type of
      surgery and follows an accurate preoperative planning in order to understand the
      specific pathologic scenario. The aim of this paper is to review some technical
      options for the revision of the acetabular component also taking into account our
      personal experiences and series.

PMID- 21082581
TI  - The multifaceted etiology of acetabular labral tears.
AB  - Acetabular labral tears have been the focus of much attention in recent years.
      With the increased use of hip arthroscopy and magnetic resonance arthrography,
      the infrequent labral tear has proved to be more prevalent than previously
      thought. The majority of labral tears occur due to an underlying anatomic
      abnormality. Anatomic abnormalities that can lead to labral tears include
      femoracetabular impingement, acetabular retroversion, abnormal femoral head, Legg
      Calve Perthes, slipped capital epiphysis, capsular laxity, and dysplasia of the
      hip. Tears in the labrum may lead to the advancement of osteoarthritis. Optimal
      management of a labral tear may involve addressing underlying anatomic
      abnormalities in addition to the labral tear itself.

PMID- 21082582
TI  - Femoral revision with taper stems: results at ten years follow-up.
AB  - In the case of extensively damaged meta-diaphyseal femoral bone with cortices
      thinning and widened femoral canal, tapered stems allow a good primary fixation
      and early weight-bearing. A retrospective review was conducted to evaluate long
      term results of modular revision taper stems implanted from March 1999 to
      December 2002. Sixty-five consecutive hip revision surgeries were performed,
      mostly for aseptic loosening (75% of the cases). Femoral bone stock defects were
      classified according to AAOS's criteria and consisted mainly in type II (cavitary
      defects, 44.6%) and type III (combined defects, 33.9%). A trochanteric osteotomy
      was performed in 25 cases (38%) to remove primary implants that were cemented in
      35 cases (54%). The mean postoperative follow-up was 109 months (range, 76 to 131
      months). Clinical assessment at follow-up showed a significantly improved mean
      Harris Hip Score from 42 points preoperatively to 81 points postoperatively,
      while the x-ray examination did show a satisfactory distal integration of the
      stem in all cases and satisfactory reconstitution of the femoral bone stock in
      47% of cases. The average subsidence of the stem at follow-up was less than one
      millimeter. According to data analysis, a leg-length discrepancy exceeding 15
      millimeters caused significantly worse functional outcome and pain.

PMID- 21082583
TI  - A novel method for prevention of intraoperative fracture in cementless hip
      arthroplasty: vibration analysis during femoral component insertion.
AB  - Emerging minimally invasive surgery (MIS) techniques in hip arthroplasty heralded
      an increase in intraoperative femoral periprosthetic fractures, likely due to
      diminished visibility, auditory, and tactile feedback. This study attempts to
      identify a method to supplement the surgeon's tactile and auditory senses by
      analyzing vibration characteristics during femoral component impaction. A
      cementless femoral component was instrumented with accelerometers and a
      piezoelectric (PZT) patch. Data was obtained during implant impaction into
      replicate femurs. Acceleration measurements were obtained and signal processing
      techniques were applied. Metrics were analyzed from PZT excitation data. The two
      most correlative indices are the frequency of the anti-resonance in the 10.5 to
      12 kHz band and the peak magnitude in the 9 to 11 kHz band. Both demonstrate good
      convergence as the prosthesis is inserted. Impact test data revealed the sum of
      the acceleration divided by the sum of the impact force demonstrates good
      convergence with implant insertion. This pattern of convergence indicates these
      two indices may demonstrate the ability to accurately predict optimal implant
      seating. This methodology is promising and has the potential to enable
      intraoperative determination of maximal femoral component seating and provide the
      surgeon valuable information to potentially prevent intraoperative fractures.

PMID- 21082584
TI  - Strategies to reduce blood loss in lower extremity total joint arthroplasty.
AB  - Concerns about blood loss and the safety of allogenic blood transfusion have led
      to the development of many transfusion options for lower extremity joint
      arthroplasty. Techniques for dealing with such blood loss include allogenic blood
      transfusion, autologous donation and transfusion, hemodilution, perioperative
      blood salvage, intraoperative cell savers, bipolar sealers, and pharmacological
      agents. A blood management strategy must consider both the patient and the
      surgical procedure, assess the transfusion risks, and formulate a plan to address
      them appropriately. This article is an overview of the blood management
      techniques for lower extremity joint arthroplasty. The purpose of this review is
      to report our opinion regarding the use of alternative blood management
      strategies and to discuss the possible advantages and disadvantages of each
      technique. The results of this review indicate that a patient-focused algorithm
      using one or more strategies such as preoperative administration of
      erythropoietin, preoperative autologous blood donation, use of a bipolar sealer,
      intraoperative blood collection and reinfusion, as well as postoperative
      reinfusion drains may reduce the need for allogenic blood transfusions in
      patients undergoing primary and revision lower-extremity joint arthroplasties.
      The authors believe that a patient-specific algorithm utilizing the
      aforementioned techniques can lead to a substantial decrease in morbidity and
      mortality and an overall cost saving for both patients and medical institutions.

PMID- 21082585
TI  - Surgeon perceptions regarding custom-fit positioning technology for total knee
      arthroplasty.
AB  - Recently, studies have begun to assess the use of custom-fit arthroplasty sytsems
      that use magnetic resonance imaging to determine component placement. The purpose
      of this study was to assess how commonly this new technique is being used by
      surgeons and whether they perceive any benefits to their patients and/or to their
      practices. Fifty orthopaedic surgeons responded to a 19-question survey regarding
      custom-fit positioning total knee arthroplasty as part of a regional orthopaedic
      meeting. Overall, 10 of the 50 surgeons surveyed reported using custom-fit
      positioning technology. Of the remaining questionnaire participants, 29 of 40
      indicated that they were interested in trying the new technique. The two reasons
      that were most frequently cited by the surgeons who were not interested in
      adopting the technique were costs and not enough clinical outcomes reports. The
      results of the present study suggest that if additional clinical studies at
      longer-term follow-up support these findings, then more surgeons may adopt this
      technique. Although cost was a perceived barrier to using this technique, the
      results of this survey suggest that some surgeons who use this technique may have
      reduced procedure time.

PMID- 21082586
TI  - Hemostasis in anterior supine intermuscular total hip arthroplasty: pilot study
      comparing standard electrocautery and a bipolar sealer.
AB  - Previous studies have demonstrated that using a bipolar sealer device for
      hemostasis in hip and knee arthroplasty results in a decreased blood loss and
      transfusion requirement. The anterior supine intermuscular total hip arthroplasty
      is a minimally invasive approach with a faster initial recovery compared with
      more traditional hip replacement surgery. A retrospective consecutive series of
      100 anterior supine total hip arthroplasties performed by one surgeon was
      reviewed. In the first 50 cases, traditional electrocautery was used. In the
      second 50 cases, a bipolar sealer device was used. No significant differences
      with operative times, intraoperative blood loss, postoperative hemoglobin levels,
      and length of hospitalization were demonstrated between the two groups. There was
      a lower rate of intraoperative and postoperative transfusions in the bipolar
      sealer group.

PMID- 21082587
TI  - Secure tracks device improves functional recovery and pain after total knee
      arthroplasty: a prospective, randomized, pilot study.
AB  - This prospective, randomized study compares functional outcomes between a novel
      support device (Secure TracksTM) and a standard walker following unilateral total
      knee replacement. Thirty patients were randomized for the study; 15 walker
      patients (70.7+/-6.4 yrs) and 15 Secure Track patients (68.2+/-6.7 yrs) (p=0.31).
      Total distance walked during all therapy sessions was nearly two times greater in
      the Secure Track (2,332 ft) than with the walker (1,241 ft)(p=.053). This trend
      began on the day of surgery (275 ft vs. 176 ft, p<.069) and was statistically
      significant by the following morning (287 ft vs. 151 ft, p=.019). Patients in the
      Secure Track spent a greater amount of time up and ambulating with the therapists
      in all sessions (.006<p>.30). At the first clinical follow-up, patients that had
      walked in the Secure Track completed the timed up and go test (TUG), a predictor
      of fall risk, 3 seconds faster than the standard rehabilitation group (9.6 vs.
      12.9 seconds, p<.091). The novel therapy patients demonstrated significantly
      greater pain relief following the TUG test (p=.005). This study demonstrates that
      the choice of support device can increase patient ambulation following surgery,
      which will in turn improve functional outcomes and pain relief.

PMID- 21082588
TI  - Innovative grid positioning system (GPS) guidance for minimally invasive spinal
      surgery.
AB  - Symptomatic degenerated spinal discs and spinal stenosis are common problems that
      can often be treated conservatively, but some require decompressive spinal
      surgery for relief. Traditional open spinal discectomy is associated with
      significant tissue trauma, higher morbidity and complication rates, a longer
      convalescence, and even destabilization of the spine. The trend of spinal surgery
      is rapidly moving toward less traumatic minimally invasive spine surgery
      (MISS).1,2 The problem that faces the surgeon performing endoscopic MISS is that
      it is done with limited surgical exposure and visualization of the surgical
      field. The surgical field can only be viewed through an endoscope to correlate
      the lesion/pathology in relationship to imaging studies aided by C-arm
      fluoroscopy. In response, a logical and simple Grid Positioning System (GPS) was
      developed to provide a precise surgical trajectory/approach for the disc lesion
      to undergo decompression. GPS involves 3D geometric triangulation of 3 different
      planes guided by fluoroscopy for introduction of surgical instruments along a
      geometric line toward the lesion without compromising healthy anatomical
      structures. This system facilitates MISS, especially in the morbidly obese. In
      this chapter, we will describe the GPS system and its application to aid in
      facilitating minimally invasive decompressive spine surgery for alleviating
      symptoms of degenerative spinal disease, herniated disc, and spinal stenosis,
      while avoiding the complications and risks of conventional more traumatic spinal
      surgery and fusion.

PMID- 21082589
TI  - Endoscopic anterior cervical discectomy under epidurogram guidance.
AB  - Cervical discectomy is commonly required for spinal cord and nerve compression
      disorders. Currently, anterior cervical discectomy and fusion is the standard
      procedure for the treatment of cervical disc herniations and cervical
      degenerative disorders, whereas endoscopic cervical discectomy is considered an
      important alternative. Despite the advancement in surgical technology,
      endoscopically removing hard pathological tissues remains challenging. Inspired
      by lumbar epidurogram-guided decompression, we have developed an epidurogram
      guided endoscopic cervical decompression technique. The technique uses contrast
      dye through cervical discography to generate an epidurogram. Under fluoroscopic
      view, the spinal cord is posterior to the contrast line. The endoscopic
      instruments can safely reach the epidural space, if it's necessary, as long as
      they stay anterior to the contrast line. We have used this technique to treat
      both soft and hard cervical disc herniations, and we have found it makes the
      surgical procedures safer when more aggressive decompression is required.

PMID- 21082590
TI  - [Doctor, diets don't work for me - I want an operation immediately].

PMID- 21082592
TI  - [What is your diagnosis? Soft tissue emphysema after shoulder arthroscopy].

PMID- 21082593
TI  - [Highlights in gastroenterology 2010].
AB  - This summer saw the fifteenth edition of "Gastro-Highlights", a well-attended
      symposium dedicated to continuing education that takes place each year at the
      University Hospital in Zurich. Major new findings in the fields of
      gastroenterology and hepatology that were achieved in the past year and were
      recently presented at the "Digestive Disease Week (DDW)" were summarized here for
      practising gastroenterologists and internists.

PMID- 21082594
TI  - [The concept of chronic disease in the palliative treatment of oncologic
      patients: current Swiss data and insights in the context of breast and ovarian
      cancer].
AB  - In the last years, incurable oncologic diseases have become increasingly viewed
      as chronic disease processes. In order to evaluate the treatment course of a
      chronic disease and to demonstrate whether the concept of a palliative oncologic
      situation as a chronic disease can be translated into practice, it is essential
      to give an overview of the entire course of the disease (i.e. from the first
      diagnosis of recurrence/metastases to death). There are only few reports
      regarding this approach in the international literature. We present Swiss long
      term data (1990-2007) for breast and ovarian cancer and demonstrate drawbacks and
      opportunities of an exact retrospective data collection and analysis. When an
      incurable disease which requires periodic therapy cycles to control progressive
      course and symptoms is increasingly treated with a strategy that permits
      stabilization and uses regimens that have limited cumulative toxicity with
      particular consideration of quality of life, then the requirements of a chronic
      disease management have been fulfilled.

PMID- 21082595
TI  - [Photochemical internalisation (PCI): a further development of photodynamic
      therapy for the treatment of skin cancer].
AB  - Recently, several new and non-invasive methods have been introduced for the
      treatment of skin cancers. Topical creams using the immune modulator imiquimod or
      the COX inhibitor diclofenac (with hyaluronic acid) are now registered for use
      against neoplasms such as basal or squamous cell carcinoma. Another modern
      treatment option is photodynamic therapy (PDT). A refined version of PDT, namely
      photochemical internalisation, is currently subject to a first clinical trial in
      patients with osteosarcoma, squamous cell carcinoma, head and neck cancer as well
      as adenocarcinoma of the breast. Preliminary results from this trial suggest that
      PCI seems to be a promising treatment.

PMID- 21082596
TI  - [Which clinical symptoms suggest distinct autoantibody measurements?].
AB  - The detection of autoantibodies is an important cornerstone in the diagnosis of
      systemic autoimmune disorders such as autoimmune connectivitides and small vessel
      vasculitides. Antinuclear antibodies (ANAs ) and antineutrophil cytoplasmic
      antibodies (c+p-ANCAs) are appropriate diagnostic screening tools for autoimmune
      connectivitides and small vessel vasculitides. For economic and
      intellectual/didactic reasons more extensive autoantibody diagnostics should be
      performed only in particular situations when patients history and clinical exam
      lead to strong diagnostic suspicion.

PMID- 21082597
TI  - [Vitamin B deficiency].

PMID- 21082598
TI  - [Lorcaserin for weight reduction for overweight and adipose adults].

PMID- 21082599
TI  - [Rimonabant is associated with serious neuropsychiatric side effects].

PMID- 21082601
TI  - [CME EKG 31. EKG changes. Anterior wall myocardial infarct].

PMID- 21082602
TI  - [Physician art column. A new era in art in Vienna].

PMID- 21082603
TI  - [2 Milieu studies from the demimonde].

PMID- 21082615
TI  - Diagnosing macular edema with certitude at an early stage has proven difficult
      despite the progress of contact lens biomicroscopy. Preface.

PMID- 21082620
TI  - Facile syntheses and tunable non-linear optical properties of heterothiometallic
      clusters with [MS4Ag2] units (M=Mo, W).

PMID- 21082622
TI  - Introduction of curvature in amphipathic oligothiophenes for defined aggregate
      formation.
AB  - In this study the possibility to control the size and shape of self-assembled
      structures through the local curvature of their molecular building blocks has
      been investigated. To this end a series of amphipathic conjugated oligothiophenes
      with a well-defined curvature of their backbone has been designed and
      synthesized. The molecular (local) curvature of these oligothiophenes resulted
      from a preference for cis instead of trans conformations at specific positions
      along the oligothiophene backbone, which can be controlled by the sequence of
      hydrophilic and hydrophobic groups, while their ratio was kept constant. The self
      assembly of ter-, sexi-, and dodecathiophenes appeared to be a low-cooperative
      process, involving the formation of premicellar aggregates at sub-millimolar
      concentrations, which at concentrations in the millimolar regime transformed into
      micelles and cylindrical micelles. The aggregates display fine structures with
      dimensions reminiscent of the thiophene molecules. The structure-morphology
      relationship of the ter- and sexithiophenes could be described by conventional
      packing theory. However, with the dodecathiophene, the backbone curvature
      governed the formation of cylindrical aggregates with a well-defined diameter.
      These results demonstrate that it is possible to control the aggregation
      morphology of simple amphipathic oligothiophenes by implementation of an
      additional structural motif namely, the curvature.

PMID- 21082623
TI  - Comparing the enantioselective power of steric and electrostatic effects in
      transition-metal-catalyzed asymmetric synthesis.
AB  - The current approach to improve and tune the enantioselective performances of
      transition-metal catalysts for asymmetric synthesis is mostly focused to
      modifications of the steric properties of the ancillary ligands of the active
      metal. Nevertheless, it is also known that electrostatic effects can have a
      remarkable role to promote selectivity in asymmetric synthesis. Using the Rh
      catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone
      leading to chiral 3-phenylcyclohexanone as an example, we could show that high
      enantioselectivity can be indeed achieved using catalysts essentially based
      either on steric or electrostatic effects as the main source of enantioselective
      induction. In this contribution we suggest that the analysis of the surface of
      interaction between the catalyst and the substrate could be a useful tool to
      quantify the power of steric and electrostatic effects of catalysts.

PMID- 21082625
TI  - Dynamic kinetic asymmetric domino oxa-Michael/carbocyclization by combination of
      transition-metal and amine catalysis: catalytic enantioselective synthesis of
      dihydrofurans.

PMID- 21082627
TI  - Nonlinear effects in asymmetric amino acid catalysis by multiple interconnected
      stereoselective catalytic networks.

PMID- 21082632
TI  - The European Young Chemist Award 2010.

PMID- 21082630
TI  - Ring currents in the dismutational aromatic Si6R6.

PMID- 21082633
TI  - A highly durable platinum nanocatalyst for proton exchange membrane fuel cells:
      multiarmed starlike nanowire single crystal.

PMID- 21082635
TI  - Switchable open-cage fullerene for water encapsulation.

PMID- 21082634
TI  - Modular polymer-caged nanobins as a theranostic platform with enhanced magnetic
      resonance relaxivity and pH-responsive drug release.

PMID- 21082636
TI  - Reactivity studies of a masked three-coordinate vanadium(II) complex.

PMID- 21082638
TI  - Amplified detection of DNA through an autocatalytic and catabolic DNAzyme
      mediated process.

PMID- 21082640
TI  - Laurent Maron.

PMID- 21082639
TI  - Enantioselective total syntheses of three cladiellins (eunicellins): a general
      approach to the entire family of natural products.

PMID- 21082641
TI  - The leiodolide B puzzle.

PMID- 21082642
TI  - Lewis acid catalyzed intramolecular direct ene reaction of indoles.

PMID- 21082643
TI  - Franklinolides A-C from an Australian marine sponge complex: phosphodiesters
      strongly enhance polyketide cytotoxicity.

PMID- 21082644
TI  - Binary self-assembly of gold nanowires with nanospheres and nanorods.

PMID- 21082645
TI  - A high-performance gas-separation membrane containing submicrometer-sized metal
      organic framework crystals.

PMID- 21082653
TI  - Genetic basis of potential therapeutic strategies for craniosynostosis.
AB  - Craniosynostosis, the premature fusion of one or more cranial sutures, is a
      common malformation of the skull that can result in facial deformity and
      increased intracranial pressure. Syndromic craniosynostosis is present in ~15% of
      craniosynostosis patients and often is clinically diagnosed by neurocranial
      phenotype as well as various other skeletal abnormalities. The most common
      genetic mutations identified in syndromic craniosynostosis involve the fibroblast
      growth factor receptor (FGFR) family with other mutations occurring in genes for
      transcription factors TWIST, MSX2, and GLI3, and other proteins EFNB1, RAB23,
      RECQL4, and POR, presumed to be involved either upstream or downstream of the
      FGFR signaling pathway. Both syndromic and nonsyndromic craniosynostosis patients
      require early diagnosis and intervention. The premature suture fusion can impose
      pressure on the growing brain and cause continued abnormal postnatal craniofacial
      development. Currently, treatment options for craniosynostosis are almost
      exclusively surgical. Serious complications can occur in infants requiring either
      open or endoscopic repair and therefore the development of nonsurgical techniques
      is highly desirable although arguably difficult to design and implement. Genetic
      studies of aberrant signaling caused by mutations underlying craniosynostosis in
      in vitro calvarial culture and in vivo animal model systems have provided
      promising targets in designing genetic and pharmacologic strategies for systemic
      or adjuvant nonsurgical treatment. Here we will review the current literature and
      provide insights to future possibilities and limitations of therapeutic
      applications.

PMID- 21082654
TI  - IRF6 mutations in mixed isolated familial clefting.
AB  - Mutations in the interferon regulatory factor 6 (IRF6) gene are known to cause
      van der Woude syndrome (VWS), a common syndromic form of oro-facial clefting
      characterized by the familial occurrence of mixed clefting (cleft lip with or
      without a cleft palate and cleft palate alone in the same family) and lower lip
      pits. As lip pits are not present in all cases of VWS, IRF6 mutations can cause a
      phenotype identical to non-syndromic clefting. However, recent studies failed to
      identify IRF6 mutations in sporadic and familial non-syndromic clefting,
      concluding that testing for IRF6 was not warranted for sporadic or familial non
      syndromic clefting. Here we report on two families that demonstrate familial
      mixed clefting in which mutations in IRF6 were identified, suggesting that IRF6
      testing does have a role in familial, non-syndromic OFC.

PMID- 21082655
TI  - Molecular characterization and clinical features of a patient with an
      interstitial deletion of 3p25.3-p26.1.
AB  - Distal chromosome 3p deletions (3p- syndrome) are associated with various
      developmental defects. The majority of cases have a terminal deletion of the
      short arm of chromosome 3 with loss of either the maternal or the paternal copy.
      A girl with an interstitial molecularly characterized 1.6 Mb deletion in cytoband
      3p25.3-26.1 of the paternal chromosome 3 is presented. To our knowledge, she
      possesses the smallest deletion that has ever been reported for a patient with a
      clinical phenotype in accordance with the 3p- syndrome. The boundaries of the
      deletion lies within nearly all previously reported terminal deletions causing
      this syndrome. Selected genes that are present in the hemizygous state and which
      might be important for the phenotype of this patient as regards the congenital
      heart defect, autistic behavior and mental retardation (CAV3, OXTR, and
      SRGAP3/MEGAP, respectively) are discussed in context of the clinical features.

PMID- 21082656
TI  - Novel duplication in glypican-4 as an apparent cause of Simpson-Golabi-Behmel
      syndrome.

PMID- 21082657
TI  - Deletion of 7q34-q36.2 in two siblings with mental retardation, language delay,
      primary amenorrhea, and dysmorphic features.
AB  - We describe a chromosome rearrangement, ins(7;13)(q32q34;q32), which segregates
      in a three generation family, giving rise to three individuals with an unbalanced
      rearrangement. Two of the individuals, a sister and a brother, were investigated
      further in this study. They had minor facial dysmorphism and neuropsychiatric
      disorders including mental retardation, language delay and epilepsy. The sister
      had primary amenorrhea. Array CGH revealed a 12.2 Mb deletion at 7q34-q36.2
      including more than 60 genes where CNTNAP2 and NOBOX are of special interest.
      Comparison of the clinical and cytogenetic findings of our patients with
      previously reported patients, supports that haploinsuffiency of CNTNAP2 can
      result in language delay and/or autism spectrum disorder. Furthermore, we report
      on the second women with a deletion involving NOBOX who is affected by primary
      amenorrhea.

PMID- 21082658
TI  - Clinical report of microphthalmia and optic nerve coloboma associated with a de
      novo microdeletion of chromosome 16p11.2.
AB  - Anophthalmia and microphthalmia are etiologically and clinically heterogeneous.
      We present a 13-year-old boy with microphthalmia and multiple anomalies who was
      evaluated as part of our research into the etiology of microphthalmia. His
      clinical features included left microphthalmia, persistent hyperplastic primary
      vitreous and posterior coloboma, right posterior pole coloboma, pectus excavatum,
      mild hypotonia, mild delays in speech and motor development, and an anxiety
      disorder with social difficulties. Investigations with a chromosome microarray
      revealed a de novo deletion of chromosome 16p11.2 of approximately 882 kb in
      size. Deletions of this region of chromosome 16p11.2 are a newly delineated
      microdeletion syndrome, but this is the first report of microphthalmia and
      coloboma associated with monosomy for 16p11.2, and emphasizes the clinical
      variability that can be present with this deletion. This report contributes to
      the growing knowledge regarding this microdeletion and suggests that rare copy
      number changes may be a cause of microphthalmia and other eye anomalies.

PMID- 21082660
TI  - Symmetrical enchondromatosis is associated with duplication of 12p11.23 to
      12p11.22 including PTHLH.
AB  - We describe a patient with striking generalized symmetrical enchondromatosis of
      the tubular bones and a de novo duplication of chromosome 12p11.23 to 12p11.22.
      The PTHLH gene within this region encodes a ligand for PTHR1: mutations in the
      gene encoding this receptor are associated with some cases of Ollier disease,
      several skeletal dysplasias including Blomstrand, Eiken, and Jansen and down
      regulation of PTHLH expression in brachydactyly type E. Our findings suggest that
      abnormal PTHLH-PTHR1 signaling may underly this unusual form of enchondromatosis
      and indicate that unlike most cases of Ollier disease it is dominantly inherited.

PMID- 21082665
TI  - The need for increased acceptance and use of spatially explicit wildlife exposure
      models.

PMID- 21082667
TI  - Monitoring the tidal Delaware River for ambient toxicity.
AB  - This study assessed ambient waters in an urbanized area of the Delaware River, to
      determine whether river water samples exhibited chronic lethal or sublethal
      toxicity when measured in laboratory experiments. Toxicity was assessed at 16
      fixed stations in the main-stem river and 29 stations in tributaries of the tidal
      Delaware River with salinities from 0 to 15 parts per 1000 (ppt) using Pimephales
      promelas, Americamysis bahia, Menidia beryllina, and Ceriodaphnia dubia in 7-d
      tests; Pseudokirchneriella subcapitata in a 96-h test; and Hyalella azteca in a
      10-d water-only test. The toxicity tests measured organism survival, growth, and
      reproduction. Results from testing water samples collected in 4 different y
      indicated that the samples from sites tested in the main-stem of the Delaware
      River and from the majority of its tributaries did not produce chronic toxicity.
      The surveys identified tributaries that warrant further assessment for toxicity.

PMID- 21082666
TI  - Using field data to assess the effects of pesticides on crustacea in freshwater
      aquatic ecosystems and verifying the level of protection provided by water
      quality guidelines.
AB  - The purpose of this study was to investigate how well single-species laboratory
      data predict real-world pesticide toxicity effects on Crustacea. Data from field
      pesticide exposures from experimental mesocosm and small pond studies were
      converted into toxicity units (TUs) by dividing measured pesticide concentrations
      by the L(E)C50 for Daphnia or acute 5% hazard concentration for Crustacea (HC5
      C). The proportion of crustacean taxa significantly affected by the pesticide
      treatment, called the count ratio of effect, was used in logistic regression
      models. Of 200 possible logistic model combinations of the TUs, fate,
      physicochemical variables, and structural variables versus the count ratio of
      effect for the mesocosm data, the best model was found to incorporate log(TU HC5
      C). This model was used to convert pesticide water quality guidelines from around
      the world into estimates of the proportion of crustacean taxa predicted to be
      impacted by exposure to a pesticide at the water quality guideline concentration.
      This analysis suggests 64% of long-term water quality guidelines and 88% of short
      term pesticide water quality guidelines are not protective of the aquatic life
      they are designed to protect. We conclude that empirically derived data from
      mesocosm studies should be incorporated into water quality guideline derivation
      for pesticides where available. Also, interspecific differences in susceptibility
      should be accounted for more accurately to ensure water quality guidelines are
      adequately protective against the adverse effects of pesticide exposure.

PMID- 21082669
TI  - Regulatory consideration of bioavailability for metals: simplification of input
      parameters for the chronic copper biotic ligand model.
AB  - The chronic Cu biotic ligand model (CuBLM) provides a means by which the
      bioavailability of Cu can be taken into account in assessing the potential
      chronic risks posed by Cu at specific freshwater locations. One of the barriers
      to the widespread regulatory application of the CuBLM is the perceived complexity
      of the approach when compared to the current systems that are in place in many
      regulatory organizations. The CuBLM requires 10 measured input parameters,
      although some of these have a relatively limited influence on the predicted no
      effect concentration (PNEC) for Cu. Simplification of the input requirements of
      the CuBLM is proposed by estimating the concentrations of the major ions Mg2+,
      Na+, K+, SO4(2-), Cl- , and alkalinity from Ca concentrations. A series of
      relationships between log10 (Ca, mg l(-1)) and log10 (major ion, mg l(-1)) was
      established from surface water monitoring data for Europe, and applied in the
      prediction of Cu PNEC values for some UK freshwater monitoring data. The use of
      default values for major ion concentrations was also considered, and both
      approaches were compared to the use of measured major ion concentrations. Both
      the use of fixed default major ion concentrations, and major ion concentrations
      estimated from Ca concentrations, provided Cu PNEC predictions which were in good
      agreement with the results of calculations using measured data. There is a slight
      loss of accuracy when using estimates of major ion concentrations compared to
      using measured concentration data, although to a lesser extent than when fixed
      default values are applied. The simplifications proposed provide a practical
      evidence-based methodology to facilitate the regulatory implementation of the
      CuBLM.

PMID- 21082674
TI  - Comprehensive analysis of low-abundance proteins in human urinary exosomes using
      peptide ligand library technology, peptide OFFGEL fractionation and nanoHPLC-chip
      MS/MS.
AB  - Human urinary exosomes are 30-100 nm vesicles that originate as the internal
      vesicles in multivesicular bodies from every renal epithelial cell type facing
      the urinary track and may serve as a suitable noninvasive starting material for
      biomarker discovery relevant to a variety of renal disease. To comprehensively
      explore the low-abundance proteome, combinatorial peptide ligand libraries,
      combined with peptide OFFGEL electrophoresis were employed for the enrichment and
      separation of relatively low-abundant proteins in urinary exosomes. After
      analysis by nanoHPLC-chip-MS/MS, 512 proteins were identified, including a large
      number of proteins with extreme molecular weight or extreme pI value, which could
      not be well mapped by using traditional 2-D-gel-based separation methods. This in
      depth analysis of low-abundant proteins in urinary exosomes led to an increased
      understanding of molecular composition of these little vesicles and may be
      helpful for the discovery of novel biomarker. Our work also provides an effective
      strategy of concentration and identification of low-abundance proteome from
      complex bio-samples.

PMID- 21082675
TI  - Sensitivity enhancement of CE and CE-MS for the analysis of peptides by a dynamic
      pH junction.
AB  - An analytical method of CE-MS and CE with an online preconcentration technique
      induced by a dynamic pH junction, addition of organic solvent and large volume
      injection was developed for sensitive determination of peptides in biological
      samples. Leucine enkephalin, methionine enkephalin, dynorphin A, beta-endorphin
      and angiotensin II were used as model peptides. The optimal online
      preconcentration conditions were obtained at a sample matrix consisting of 100 mM
      borate buffer (pH 10.0) with 50% v/v acetonitrile and a BGE containing 1 M formic
      acid at pH 2.0, along with a 25-cm injection length. Under the optimized
      conditions, a 4.0*10(3)-1.1*10(4)-fold increase in peak intensity was achieved
      without degrading the peak shape. This online preconcentration method was applied
      to analyze the intracellular angiotensin II within the peptides extracted from
      HL1 cells and approximately increase of 1*10(4)-fold sensitivity was achieved
      compared to normal condition. Thus, the developed method could be applied to the
      analysis of various peptides for peptidomics study in biological samples.

PMID- 21082676
TI  - Room temperature ionic liquid-mediated molecularly imprinted polymer monolith for
      the selective recognition of quinolones in pork samples.
AB  - A novel molecularly imprinted polymer monolith was prepared by the room
      temperature ionic liquid-mediated in situ molecular imprinting technique, using
      norfloxacin (NOR) as the template, methacrylic acid as the functional monomer,
      ethylene glycol dimethacrylate as the cross-linker. The optimal synthesis
      conditions and recognition properties of NOR-imprinted monolithic column were
      investigated. The results indicated that the imprinted monoliths exhibited good
      ability of selective recognition against the template and its structural analog.
      Using the fabricated material as solid-phase extraction sorbent, a sample pre
      treatment procedure of molecularly imprinted solid-phase extraction coupling with
      HPLC was developed for determination of trace quinolone residues in animal
      tissues samples. The recoveries ranging from 78.16 to 93.50% for eight quinolones
      antibiotics such as marbofloxacin, NOR, ciprofloxacin, danofloxacin, difloxacin,
      oxolinic acid, flumequine and enrofloxacin were obtained.

PMID- 21082678
TI  - Determination of amoxapine and nortriptyline in blood plasma and serum by salt
      assisted liquid-liquid microextraction and high-performance liquid
      chromatography.
AB  - A new, selective and sensitive method has been developed for the determination of
      tricyclic antidepressant drugs, amoxapine and nortriptyline, in human blood
      plasma and serum, involving their reaction with allyl isothiocyanate and
      extraction of thiourea derivatives with water-miscible organic solvent
      acetonitrile. The phase separation was effected by addition of ammonium sulphate,
      a process called salt-assisted liquid-liquid microextraction. The extract was
      analyzed by HPLC with UV detection at 254 nm. The method has been optimized for
      derivatization reaction time and temperature, solvent for extraction, and salt
      for solvent phase separation. Under the optimal conditions, a linear calibration
      graph was obtained between the amount of drug and the peak area of thiourea
      derivatives in the range of 0.002-20 mg/L drugs. The correlation coefficient and
      limit of detection values for amoxapine and nortriptyline in serum/plasma samples
      were in the range of 0.9953-0.9999 and 0.46-0.58 MUg/L, respectively. The
      recovery in spiking experiments ranged, respectively, 75-88% (RSD 3.4-7.2%) and
      79-97% (RSD 3.7-7.9%) for the two drugs.

PMID- 21082679
TI  - Quantitative structure-property relationship modeling of water-to-wet butyl
      acetate partition coefficient of 76 organic solutes using multiple linear
      regression and artificial neural network.
AB  - The main aim of this study was the development of a quantitative structure
      property relationship method using an artificial neural network (ANN) for
      predicting the water-to-wet butyl acetate partition coefficients of organic
      solutes. As a first step, a genetic algorithm-multiple linear regression model
      was developed; the descriptors appearing in this model were considered as inputs
      for the ANN. These descriptors are principal moment of inertia C (I(C)), area
      weighted surface charge of hydrogen-bonding donor atoms (HACA-2), Kier and Hall
      index (order 2) ((2)chi), Balaban index (J), minimum bond order of a C atom
      (P(C)) and relative negative-charged SA (RNCS). Then a 6-4-1 neural network was
      generated for the prediction of water-to-wet butyl acetate partition coefficients
      of 76 organic solutes. By comparing the results obtained from multiple linear
      regression and ANN models, it can be seen that statistical parameters (Fisher
      ratio, correlation coefficient and standard error) of the ANN model are better
      than that regression model, which indicates that nonlinear model can simulate the
      relationship between the structural descriptors and the partition coefficients of
      the investigated molecules more accurately.

PMID- 21082680
TI  - Fully automated determination of N-nitrosamines in environmental waters by
      headspace solid-phase microextraction followed by GC-MS-MS.
AB  - A fully automated method for determining nine Environmental Protection Agency N
      nitrosamines in several types of environmental waters at ng/L levels is
      presented. The method is based on a headspace solid-phase microextraction
      followed by GC-MS-MS using chemical ionization. Three different fibers
      (carboxen/PDMS, divinylbenzene/carboxen/PDMS, and PEG) were tested. Solid-phase
      microextraction conditions were best when a divinylbenzene/carboxen/PDMS fiber
      was exposed for 60 min in the headspace of 10 mL water samples at pH 7 containing
      360 g/L of NaCl, at 45 degrees C. All compounds were analyzed by GC-MS-MS within
      18 min. The method was validated using effluent from an urban wastewater
      treatment plant and the LODs ranged from 1 to 5 ng/L. The method was then applied
      to determine the N-nitrosamines in samples of different complexities, such as tap
      water and several influent and effluent wastewater samples from urban and
      industrial wastewater treatment plants and a potable water treatment plant.
      Although the analysis of influent industrial wastewater revealed high
      concentrations of some compounds (N-nitrosomorpholine and N-nitrosodimethylamine
      at MUg/L levels), in industrial effluents and other samples, the concentrations
      were substantially lower (ng/L levels). The new method is suitable for the simple
      and reliable determination of N-nitrosamines in highly complex water samples in a
      completely automated procedure.

PMID- 21082683
TI  - Variability in dental caries prevalence between male and female foragers from the
      Late/Final Jomon period: Implications for dietary behavior and reproductive
      ecology.
AB  - OBJECTIVES: This study documents sex differences in dental caries prevalence
      among Late to Final Jomon period (4000 through 2300 BP) foragers from Japan and
      interprets the results within behavioral, dietary, and reproductive context.
      METHODS: The presence/absence of carious lesions was recorded from ~1600
      Late/Final Jomon period teeth. Frequencies and mean numbers of carious teeth were
      compared between males and females according to age, tooth group, and region
      using Fisher's exact and t tests. RESULTS: Significantly greater frequencies of
      carious molar teeth were observed in females compared to males in each age group.
      Few differences were observed between older and younger females as well as
      between females from high and low density regions. Significantly greater
      prevalence of cariogenic molars were, however, observed between females in Age
      Group 3 from a high compared to low density region. Significantly greater average
      numbers of carious molar teeth were found in females compared to males, with no
      significant differences in mean number of carious teeth between age groups.
      CONCLUSIONS: Differences in carious teeth between the sexes likely reflect
      behavioral and dietary variation for males and females. Limited differences in
      caries prevalence and mean number of carious teeth between female age groups and
      regions of varying population density suggests that reproductive factors played a
      minor role in dental caries variation between males and females.

PMID- 21082684
TI  - Mitochondrial DNA variability in the Titicaca basin: Matches and mismatches with
      linguistics and ethnohistory.
AB  - OBJECTIVES: The Titicaca basin was the cradle of some of the major complex
      societies of pre-Columbian South America and is today home to three surviving
      native languages: Quechua, Aymara, and Uro. This study seeks to contribute to
      reconstructing the population prehistory of the region, by providing a first
      genetic profile of its inhabitants, set also into the wider context of South
      American genetic background. METHODS: We report the first mitochondrial DNA first
      hypervariable segment sequences of native populations of the environs of Lake
      Titicaca: speakers of Aymara and Quechua, and the "Uros" of the Lake's floating
      islands. We sampled Aymara speakers from a locality where the Uro language was
      formerly documented, to check for possible language shift patterns. These data
      are compared with those for other Amerindian populations, collated from already
      published sources. RESULTS: Our results uncover the genetic distinctiveness of
      our formerly Uro but now Aymara-speaking sample, in contrast with a relative
      homogeneity for all the other Central Andean samples. CONCLUSIONS: The genetic
      affinities that characterize Central Andean populations are highly consistent
      with the succession of expansive polities in the region, culminating with the
      Incas. In the environs of Lake Titicaca, however, one subset of the present day
      Aymara-speaking population exhibits a peculiar position: perhaps a genetic
      correlate to their original Uro linguistic lineage (now extinct in the area),
      tallying with ethnohistorical claims for the distinctiveness of the Uro
      population. Our results emphasize the need for genetic descriptions to consider
      the widespread phenomenon of language shift.

PMID- 21082685
TI  - The thrifty phenotype: An adaptation in growth or metabolism?
AB  - The thrifty phenotype hypothesis is widely used to interpret associations between
      early nutritional experience and degenerative disease risks. However, it remains
      unclear what is adaptive about early life thrift, and biomedical approaches
      struggle to explain why associations between early growth and later disease hold
      across the entire range of birth size. This issue can be addressed using a simple
      model, attributing disease to a high metabolic load (large tissue masses, rich
      diet, and sedentary lifestyle) relative to metabolic capacity (physiological
      traits contingent on fetal/infant development). In this context, different
      hypotheses regarding the long-term functions of thrift can be examined. The
      "predictive adaptive response" hypothesis considers thrift to involve metabolic
      adaptations (insulin resistance and central adiposity) that emerge in
      anticipation of a poor quality adult breeding environment. The competing
      "maternal capital" hypothesis considers thrift to involve reductions in lean mass
      and organ phenotype arising through constraints on maternal phenotype, reflecting
      both maternal developmental experience and current ecological conditions. This
      hypothesis assumes offspring developmental responses to stresses such as
      temperature, altitude, and nutritional ecology occur under the influence of
      maternal capital indices, including size, physiology, reproductive history and
      social status. I argue that insulin resistance only emerges after infancy, and
      far from being anticipatory of a low nutritional plane, indicates perturbations
      of metabolism. Following exposure of early thrifty growth to the obesogenic
      niche. Thrift as early growth variability represents a plausible profile of
      developmental plasticity for human evolutionary history, aiding understand how
      the modern obesogenic environment interacts with physiological variability to
      induce disease.

PMID- 21082687
TI  - Cancer biology and genomics: translating discoveries, transforming pathology.
AB  - Advances in our understanding of cancer biology and discoveries emerging from
      cancer genomics are being translated into real clinical benefits for patients
      with cancer. The 2011 Journal of Pathology Annual Review Issue provides a
      snapshot of recent rapid progress on multiple fronts in the war on cancer or,
      more precisely, the wars on cancers. Indeed, perhaps the most notable recent
      shift is reflected by the sharp increase in understanding the biology of multiple
      specific cancers and using these new insights to inform rationally targeted
      therapies, with often striking successes. These recent developments, as reviewed
      in this issue, show how the long-term investments in basic cancer research are
      finally beginning to bear fruit.

PMID- 21082690
TI  - Bedside diagnosis of rippling muscle disease.

PMID- 21082689
TI  - Hindlimb skeletal muscle function in myostatin-deficient mice.
AB  - Absence of functional myostatin (MSTN) during fetal development results in adult
      skeletal muscle hypertrophy and hyperplasia. To more fully characterize MSTN loss
      in hindlimb muscles, the morphology and contractile function of the soleus,
      plantaris, gastrocnemius, tibialis anterior, and quadriceps muscles in male and
      female null (Mstn(-/-)), heterozygous (Mstn(+/-)), and wild-type (Mstn(+/+)) mice
      were investigated. Muscle weights of Mstn(-/-) mice were greater than those of
      Mstn(+/+) and Mstn(+/-) mice. Fiber cross-sectional area (CSA) was increased in
      female Mstn(-/-) soleus and gastrocnemius muscles and in the quadriceps of male
      Mstn(-/-) mice; peak tetanic force in Mstn(-/-) mice did not parallel the
      increased muscle weight or CSA. Male Mstn(-/-) muscle exhibited moderate
      degeneration. Visible pathology in male mice and decreased contractile strength
      relative to increased muscle weight suggest MSTN loss results in muscle
      impairment, which is dose-, sex-, and muscle-dependent.

PMID- 21082693
TI  - Changes in clinicopathological features and survival after gastrectomy for
      gastric cancer over a 20-year period.
AB  - BACKGROUND: The pattern of gastric cancer in the Western world is changing, with
      an increased proportion of tumours in the upper stomach. The aim of this study
      was to investigate changes in clinicopathological features and survival of
      patients with resected gastric cancer at a single institution, in an area of high
      incidence in the Far East. METHODS: Clinical features and pathological findings
      were compared in patients with gastric cancer who underwent gastrectomy at Seoul
      National University Hospital during four consecutive periods (1986-1990, 1991
      1995, 1996-2000 and 2001-2006). RESULTS: There were 12 026 patients. The mean age
      increased from 53.4 years in the first period to 57.4 years in the last (P <
      0.001). The proportion of patients aged 70 years or older also increased,
      reaching 16.1 per cent in the final period. Upper-third cancer increased from 5.3
      per cent in the first period to 14.0 per cent in the fourth (P < 0.001). Early
      gastric cancer (pathological T1) increased continuously over the four time
      intervals, from 24.8 to 48.9 per cent (P < 0.001). The overall 5-year survival
      rate increased from 64.0 per cent in the first period to 73.2 per cent at the end
      (P < 0.001), and this survival improvement was apparent in patients aged 40 years
      or more. CONCLUSION: The mean age of patients with gastric cancer has increased
      during the past 20 years. The proportion of early gastric cancer and overall
      survival have gradually increased, especially in patients aged over 40 years.

PMID- 21082694
TI  - Hereditary inclusion-body myopathy associated with cardiomyopathy: report of two
      siblings.
AB  - Hereditary inclusion-body myopathy (HIBM) or distal myopathy with rimmed vacuoles
      (DMRV) is an autosomal recessive disorder characterized by preferential
      involvement of distal muscles in the lower extremities, especially the anterior
      compartment of the legs, with relative preservation of the quadriceps.This is
      referred to as quadriceps-sparing myopathy. Previous reports have revealed
      exclusive involvement in skeletal muscles. Herein we describe two siblings with
      typical HIBM/DMRV. The patients developed exertional dyspnea 20-26 years after
      disease onset. Echocardiogram revealed a cardiomyopathy in both patients. This is
      the first report of the association between HIBM/DMRV and cardiomyopathy.

PMID- 21082695
TI  - Can we accurately measure the onset latency to the first dorsal interosseous?
AB  - We present two cases with and without a latency difference of the compound muscle
      action potential (CMAP) from the abductor digiti minimi (ADM) and the first
      dorsal interosseous (FDI). In each case, onset latencies of FDI CMAPs using the
      contralateral small finger as E2 were shorter than those of belly-tendon CMAPs
      from the ADM and FDI. We conclude that onset of the belly-tendon FDI CMAP does
      not necessarily indicate initial activation of the FDI.

PMID- 21082696
TI  - New normal values for quantitative muscle ultrasound: obesity increases muscle
      echo intensity.

PMID- 21082698
TI  - The MG-QOL15 for following the health-related quality of life of patients with
      myasthenia gravis.
AB  - The MG-QOL15 is helpful in informing the clinician about the patient's perception
      of the extent of and dissatisfaction with myasthenia gravis (MG)-related
      dysfunction. The aims of this study were to determine the usefulness of the MG
      QOL15 for following individuals with MG and to guide clinical researchers who
      plan to use the MG-QOL15. We assessed sensitivity and specificity for detecting
      clinical change and evaluated test-retest reliability. Sensitivities and
      specificities of various cut-points of change in scores are presented. Also
      presented are means and standard deviations of MG-QOL15 scores for all patients
      and for subgroups of patients. The test-retest reliability coefficient was 98.6%.
      The MG-QOL15 has an acceptable longitudinal construct validity. We consider this
      instrument to be most useful for informing the clinician about the patient's
      perception and tolerance of MG-related dysfunction. More objective measures, such
      as the MG Composite, should also be used to follow disease severity.

PMID- 21082705
TI  - Solution structure of the human HSPC280 protein.
AB  - The human HSPC280 protein belongs to a new family of low molecular weight
      proteins, which is only present in eukaryotes, and is absent in fungi. The
      solution structure of HSPC280 was determined using multidimensional NMR
      spectroscopy. The overall structure consists of three alpha-helices and four
      antiparallel beta-strands and has a winged helix-like fold. However, HEPC280 is
      not a typical DNA-binding winged helix protein in that it lacks DNA-binding
      activity. Unlike most winged-helix proteins, HSPC280 has an unusually long 13
      residue (P62-V74) wing 1 loop connecting the beta3 and beta4 strands of the
      protein. Molecules of HSPC280 have a positively charged surface on one side and a
      negatively charged surface on the other side of the protein structure.
      Comparisons with the C-terminal 80-residue domain of proteins in the Abra family
      reveal a conserved hydrophobic groove in the HSPC280 family, which may allow
      HSPC280 to interact with other proteins.

PMID- 21082706
TI  - Idiosyncrasy and identity in the prokaryotic Phe-system: crystal structure of E.
      coli phenylalanyl-tRNA synthetase complexed with phenylalanine and AMP.
AB  - The crystal structure of Phenylalanyl-tRNA synthetase from E. coli (EcPheRS), a
      class II aminoacyl-tRNA synthetase, complexed with phenylalanine and AMP was
      determined at 3.05 A resolution. EcPheRS is a (alphabeta)2 heterotetramer: the
      alphabeta heterodimer of EcPheRS consists of 11 structural domains. Three of
      them: the N-terminus, A1 and A2 belong to the alpha-subunit and B1-B8 domains to
      the beta subunit. The structure of EcPheRS revealed that architecture of four
      helix-bundle interface, characteristic of class IIc heterotetrameric aaRSs, is
      changed: each of the two long helices belonging to CLM transformed into the coil
      short helix structural fragments. The N-terminal domain of the alpha-subunit in
      EcPheRS forms compact triple helix domain. This observation is contradictory to
      the structure of the apo form of TtPheRS, where N-terminal domain was not
      detected in the electron density map. Comparison of EcPheRS structure with
      TtPheRS has uncovered significant rearrangements of the structural domains
      involved in tRNA(Phe) binding/translocation. As it follows from modeling
      experiments, to achieve a tighter fit with anticodon loop of tRNA, a shift of ~5
      A is required for C-terminal domain B8, and of ~6 to 7 A for the whole N
      terminus. EcPheRSs have emerged as an important target for the incorporation of
      novel amino acids into genetic code. Further progress in design of novel
      compounds is anticipated based on the structural data of EcPheRS.

PMID- 21082710
TI  - Self-expanding metallic stents as bridge to surgery in obstructing colorectal
      cancer.
AB  - BACKGROUND: A self-expanding metallic stent (SEMS) may relieve intestinal
      obstruction to permit elective resection of colorectal cancer presenting as an
      emergency. There have been concerns regarding the oncological consequences of
      this strategy. This study evaluated outcomes in patients with potentially curable
      colorectal cancer treated with a SEMS as a bridge to surgery. METHODS: This
      retrospective study included patients with obstructing colorectal cancer in whom
      a SEMS procedure was attempted between January 2004 and August 2007. Palliative
      SEMS procedures were excluded. Outcomes for SEMS insertion and subsequent surgery
      were recorded with a focus on survival. RESULTS: SEMS insertion was attempted and
      achieved in 34 patients, of whom 30 were discharged after successful relief of
      obstruction. However, five patients needed acute surgery within 18 days owing to
      insufficient relief of obstruction (1), or tumour (3) or caecal (1) perforation,
      with one postoperative death. The remainder underwent elective surgery with no
      postoperative mortality. In all, 28 of 34 patients were stoma free after
      operation. The 3-year survival rate of all 34 patients was 74 (95 per cent
      confidence interval 53 to 86) per cent after a median follow-up of 33.7 months. A
      curative outcome was achieved in 30 patients. CONCLUSION: Although associated
      with significant short-term problems, a SEMS can be useful in converting an
      emergency into an elective situation. No adverse oncological consequences were
      identified.

PMID- 21082713
TI  - Effects of triclosan on soil microbial respiration.
AB  - The antimicrobial substance triclosan has widespread use in personal care
      products and can enter the terrestrial environment if sewage sludge is applied to
      soil. The inhibitory effects of triclosan on basal and substrate-induced
      respiration (SIR) of three different soils were investigated. Soils were dosed
      and later redosed with four nominal triclosan concentrations, and respiration
      rates were measured over time. In each soil, a significant depression in basal
      respiration was noted after initial dosing, followed by a recovery. The initial
      extent of respiration inhibition was positively related to the triclosan dose,
      i.e., respiration was most inhibited at highest triclosan concentration.
      Differences in respiration inhibition between soils at equivalent dose were
      inversely correlated with organic matter and clay content, suggesting that the
      bioavailability of triclosan might have been reduced by sorption to organic
      carbon or by physical protection in micropores. Substrate-induced respiration was
      also reduced by the addition of triclosan and subsequently recovered. After
      redosing with triclosan, basal respiration was enhanced in all soils, suggesting
      that it was acting as a substrate. However, redosing resulted in SIR inhibition
      in all treatments above 10 mg triclosan kg(-1) in all three soils, although all
      soils appeared to be more resistant to perturbation than following initial
      dosing. The present study suggests that triclosan inhibits soil respiration but
      that a subsequent acclimation of the microbial community occurs.

PMID- 21082714
TI  - Use of gene expression, biochemical and metabolite profiles to enhance exposure
      and effects assessment of the model androgen 17beta-trenbolone in fish.
AB  - The impact of exposure by water to a model androgen, 17beta-trenbolone (TRB), was
      assessed in fathead minnows using an integrated molecular approach. This included
      classical measures of endocrine exposure such as impacts on testosterone (T),
      17beta-estradiol (E2), and vitellogenin (VTG) concentrations in plasma, as well
      as determination of effects on the hepatic metabolome using proton nuclear
      magnetic resonance spectroscopy. In addition, the rates of production of T and E2
      in ovary explants were measured, as were changes in a number of ovarian gene
      transcripts hypothesized to be relevant to androgen exposure. A temporally
      intensive 16-d test design was used to assess responses both during and after the
      TRB exposure (i.e., depuration/recovery). This strategy revealed time-dependent
      responses in females (little impact was seen in the males), in which changes in T
      and E2 production in the ovary, as well as levels in plasma, declined rapidly
      (within 1 d), followed shortly by a return to control levels. Gene expression
      measurements revealed dynamic control of transcript levels in the ovary and
      suggested potential mechanisms for compensation during the exposure phase of the
      test. Proton nuclear magnetic resonance spectroscopy revealed a number of hepatic
      metabolite changes that exhibited strong time and dose dependence. Furthermore,
      TRB appeared to induce the hepatic metabolome of females to become more like that
      of males at both high test concentrations of TRB (472 ng/L) and more
      environmentally relevant levels (33 ng/L).

PMID- 21082715
TI  - Resuspension of polychlorinated biphenyl-contaminated field sediment: release to
      the water column and determination of site-specific K DOC.
AB  - Sediments from the New Bedford Harbor (NBH) U.S. Environmental Protection Agency
      (U.S. EPA) Superfund site (Massachusetts, USA), contaminated with polychlorinated
      biphenyls (PCBs), were resuspended under different water column redox conditions:
      untreated, oxidative, and reductive. The partitioning of PCBs to the overlying
      water column was measured with polyethylene samplers and compared to partitioning
      without resuspension. Greater concentrations of total aqueous (freely dissolved +
      dissolved organic carbon (DOC)-associated) PCBs were found in all resuspended
      treatments for PCBs with mid-range K(OW)s, but no difference was observed in
      total aqueous concentrations among different redox conditions. The magnitude of
      increased concentrations depended on resuspension time and congener K(OW), but
      ranged from approximately one to eight times those found without resuspension. In
      a parallel study, DOC was flocculated and removed from smaller-scale NBH sediment
      resuspensions. In situ K(DOC)s were determined and used to calculate freely
      dissolved and DOC-associated fractions of the increase in total aqueous PCB
      concentrations due to resuspension. The importance of DOC-associated PCBs
      increased with increasing K(OW). In situ K(DOC)s were approximately one to two
      orders of magnitude greater than those calculated with a commonly used linear
      free energy relationship (LFER). The present study demonstrates that resuspension
      of contaminated sediments releases PCBs to the water column, of which a
      significant fraction are DOC-associated (e.g., 28, 65, and 90% for PCBs 28, 66,
      and 110, respectively). Results also imply that site-specific PCB K(DOC)s are
      superior to those calculated with generic LFERs.

PMID- 21082716
TI  - Gene expression changes in female zebrafish (Danio rerio) brain in response to
      acute exposure to methylmercury.
AB  - Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that
      accumulates in aquatic systems. Previous studies have shown suppression of
      hormone levels in both male and female fish, suggesting effects on gonadotropin
      regulation in the brain. The gene expression profile in adult female zebrafish
      whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were
      exposed by injection to 0 or 0.5 ug MeHg/g. Gene expression changes in the brain
      were examined using a 22,000-feature zebrafish microarray. At a significance
      level of p < 0.01, 79 genes were up-regulated and 76 genes were down-regulated in
      response to MeHg exposure. Individual genes exhibiting altered expression in
      response to MeHg exposure implicate effects on glutathione metabolism in the
      mechanism of MeHg neurotoxicity. Gene ontology (GO) terms significantly enriched
      among altered genes included protein folding, cell redox homeostasis, and steroid
      biosynthetic process. The most affected biological functions were related to
      nervous system development and function, as well as lipid metabolism and
      molecular transport. These results support the involvement of oxidative stress
      and effects on protein structure in the mechanism of action of MeHg in the female
      brain. Future studies will compare the gene expression profile induced in
      response to MeHg with that induced by other toxicants and will investigate
      responsive genes as potential biomarkers of MeHg exposure.

PMID- 21082722
TI  - New cis-configured aziridine-2-carboxylates as aspartic acid protease inhibitors.
AB  - A series of 52 cis-configured 1-alkyl-3-phenylaziridine-2-carboxylates were
      synthesized as new pseudo-irreversible inhibitors of Candida albicans secreted
      aspartic acid protease 1 (SAP1), SAP2, SAP3, and SAP8. Some of the compounds,
      which were obtained as diastereomers with S,S- and R,R-configured aziridine rings
      by Cromwell synthesis of racemic (2R,3S+2S,3R)-dibromophenylpropionic acid ester
      with amines, followed by ester hydrolysis and coupling to hydrophobic amino acid
      esters, were separated by preparative HPLC. The absolute configuration of the
      aziridine ring was assigned by a combination of experimental circular dichroism
      (CD) investigations and quantum chemical CD calculations. In agreement with
      previous docking studies, the diastereomers all exhibit similar activity. The
      compounds were found to be more active against the related mammalian enzyme
      cathepsin D, presumably due to productive interactions of the N-alkyl substituent
      with the highly lipophilic S2 pocket. The most active inhibitors (5, 9, 10, 21,
      and 28), characterized by benzyl, cyclohexylmethyl, tert-butyl, or 1,4
      dimethylpentyl moieties at the aziridine nitrogen atom, exhibit k(2nd) values
      between 500 and 900*103 M-1 min-1 and K(i) values near or below 1 MUM for
      cathepsin D.

PMID- 21082721
TI  - Synthetic symmetrization in the crystallization and structure determination of
      CelA from Thermotoga maritima.
AB  - Protein crystallization continues to be a major bottleneck in X-ray
      crystallography. Previous studies suggest that symmetric proteins, such as
      homodimers, might crystallize more readily than monomeric proteins or asymmetric
      complexes. Proteins that are naturally monomeric can be made homodimeric
      artificially. Our approach is to create homodimeric proteins by introducing
      single cysteines into the protein of interest, which are then oxidized to form a
      disulfide bond between the two monomers. By introducing the single cysteine at
      different sequence positions, one can produce a variety of synthetically
      dimerized versions of a protein, with each construct expected to exhibit its own
      crystallization behavior. In earlier work, we demonstrated the potential utility
      of the approach using T4 lysozyme as a model system. Here we report the
      successful application of the method to Thermotoga maritima CelA, a thermophilic
      endoglucanase enzyme with low sequence identity to proteins with structures
      previously reported in the Protein Data Bank. This protein had resisted
      crystallization in its natural monomeric form, despite a broad survey of
      crystallization conditions. The synthetic dimerization of the CelA mutant D188C
      yielded well-diffracting crystals with molecules in a packing arrangement that
      would not have occurred with native, monomeric CelA. A 2.4 A crystal structure
      was determined by single anomalous dispersion using a seleno-methionine
      derivatized protein. The results support the notion that synthetic symmetrization
      can be a useful approach for enlarging the search space for crystallizing
      monomeric proteins or asymmetric complexes.

PMID- 21082723
TI  - Construction of heterojunction nanowires from polythiophene/polypyrrole for
      applications as efficient switches.
AB  - The design and fabrication of PTh-PPY heterojunction nanowires that exhibits
      smart responses to electrochemical redox potentials is described. In their
      oxidized state, PTh-PPY nanowires act as resistors, whilst in their reduced
      state, they acts as diodes. Furthermore, the electrical transport mode can be
      reversibly changed by alternately exposing the nanowires to negative and positive
      potentials. Constructing full-organic heterojunction nanowires with smart,
      controllable properties will contribute to the development of intelligent organic
      devices and organic-electronic circuits on the nanoscale.

PMID- 21082726
TI  - Back-scattering interferometry: a versatile platform for the study of free
      solution versus surface-immobilized hybridization.

PMID- 21082725
TI  - N-glycosylation efficiency is determined by the distance to the C-terminus and
      the amino acid preceding an Asn-Ser-Thr sequon.
AB  - N-glycosylation is the most common and versatile protein modification. In
      eukaryotic cells, this modification is catalyzed cotranslationally by the enzyme
      oligosaccharyltransferase, which targets the beta-amide of the asparagine in an
      Asn-Xaa-Ser/Thr consensus sequon (where Xaa is any amino acid but proline) in
      nascent proteins as they enter the endoplasmic reticulum. Because modification of
      the glycosylation acceptor site on membrane proteins occurs in a compartment
      specific manner, the presence of glycosylation is used to indicate membrane
      protein topology. Moreover, glycosylation sites can be added to gain topological
      information. In this study, we explored the determinants of N-glycosylation with
      the in vitro transcription/translation of a truncated model protein in the
      presence of microsomes and surveyed 25,488 glycoproteins, of which 2,533
      glycosylation sites had been experimentally validated. We found that
      glycosylation efficiency was dependent on both the distance to the C-terminus and
      the nature of the amino acid that preceded the consensus sequon. These findings
      establish a broadly applicable method for membrane protein tagging in topological
      studies.

PMID- 21082728
TI  - Hydrogen production from bioethanol: Oxidative steam reforming of aqueous ethanol
      triggered by oxidation of Ni/Ce0(.)5Zr0(.)5O2-(x) at low temperature.

PMID- 21082733
TI  - Comparative anatomical study of the forearm extensor muscles of Cebus libidinosus
      (Rylands et al., 2000; Primates, Cebidae), modern humans, and other primates,
      with comments on primate evolution, phylogeny, and manipulatory behavior.
AB  - Despite its abundance in Latin America, and its remarkable ability to use tools,
      there are only a few myological studies on the capuchin monkey, Cebus
      libidinosus. In the present study, we dissected the forearm extensor muscles of
      six adult males and two adult females of this species. We describe these muscles
      and compare them with those of other primates dissected by us and by other
      authors. The forearm extensor muscles of Cebus monkeys are, in general, more
      similar to those of other platyrrhines than to distantly related taxa that use
      tools, such as chimpanzees and modern humans, with three main exceptions:
      contrary to most other platyrrhines, (1) in Cebus, chimpanzees and modern humans
      the extensor pollicis longus usually inserts onto Digit I, and not onto Digits I
      and II; (2) in Cebus the abductor pollicis longus has two separate tendons, as is
      the case in chimpanzees, and in modern humans (where one of these tendons is
      associated with a distinct belly, forming the muscle extensor pollicis brevis);
      (3) in Cebus, and in modern humans and chimpanzees, the extensor pollicis longus
      is not deeply blended with the extensor indicis. Therefore, the Cebus monkeys
      provide an illustrative example of how phylogenetic constrains and ecological
      adaptations have been combined to develop a specific myological configuration
      that, associated with their sophisticated neurological organization, allow them
      to easily navigate in their arboreal habitats and, at the same time, to finely
      manipulate objects in order to search for food and to prepare this food for
      ingestion.

PMID- 21082737
TI  - Proximal testicular ducts of the Mediterranean gecko (Hemidactylus turcicus).
AB  - The efferent ducts of the Mediterranean Gecko, Hemidactylus turcicus (Gekkonidae)
      were investigated using light and electron microscopy. The seminiferous tubules
      unite into a single rete testis tubule. The rete testis divides into 3-4 ductuli
      efferentes which all drain into the cranial portion of the ductus epididymis. All
      efferent ducts are most active during the months of December to August. The rete
      testis is composed of a simple squamous epithelium with bifurcated nuclei and a
      labyrinthine network of intercellular canaliculi. Ciliated and nonciliated cells
      are present, and more than one cilium extends from the scattered ciliated cells.
      The presence of small clear vesicles and widened intercellular canaliculi suggest
      that cells of the rete testis are responsible for intake of luminal fluids. The
      ductuli efferentes are composed of a simple cuboidal epithelium consisting of
      ciliated and nonciliated cells, and ciliated cells are the dominant cell type.
      During the inactive season the number of lysosomes increases and the cells become
      spermiophagic. The ductus epididymis is composed of a tall pseudostratified
      columnar epithelium with relatively scarce basal cells. No evidence for
      regionalization was observed. The ductus epididymis is highly secretory during
      the active season with numerous electron-dense secretory granules, whose
      glycoprotein products are released by merocrine secretion. Basally, the active
      epididymis has swollen intercellular canaliculi and enlarged cisternae of rough
      endoplasmic reticulum. During the inactive season the secretory activity
      decreases and membranous structures and fibrous material are observed within
      widened intercellular canaliculi apical to the basal cells.

PMID- 21082738
TI  - Serum peptidome profiling in patients with lung cancer.
AB  - Serum peptide profiling is a promising approach for classification of cancer
      versus noncancer samples. In this study, we aimed to search for discriminating
      peptide patterns in serum samples between lung cancer patients and healthy
      controls. The magnetic beads-based weak cation-exchange chromatography followed
      by matrix-assisted laser desorption and ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) was used in this study to identify patients with lung
      cancer. In total, serum samples from 64 lung cancer patients (32 for training set
      and 32 for testing set), 64 healthy controls (32 for training set and 32 for
      testing set), and 10 COPD patients (for disease control) were analyzed in this
      study. The mass spectra data analyzed with ClinProTools software was used to
      distinguish between cancer patients and healthy individuals based on three
      different algorithm models (GA, SNN, and QC). In the training set, patients with
      lung cancer could be identified with the mean sensitivity of 98.9% and
      specificity of100%. Similar results could be obtained from testing set, showing
      87% sensitivity and 84.8% specificity. Screening for serum peptide patterns using
      MALDI-TOF MS showed high sensitivity and specificity in identifying patients with
      lung cancer.

PMID- 21082741
TI  - Morphology of the lumbar transversospinal muscles examined in a mouse bearing a
      muscle fiber-specific nuclear marker.
AB  - Although the morphology of human lumbar transversospinal (TSP) muscles has been
      studied, little is known about the structure of these muscles in the mouse (Mus
      musculus). Such information is relevant given mice are often used as a "normal"
      phenotype for studies modeling human development. This study describes the gross
      morphology, muscle fiber arrangement, and innervation pattern of the mouse lumbar
      TSP muscles. A unique feature of the study is the use of a transgenic mouse line
      bearing a muscle-specific nuclear marker that allows clear delineation of muscle
      fiber and connective tissue boundaries. The lumbar TSP muscles of five mice were
      examined bilaterally; at each spinal level muscles attached to the caudal edge of
      the spinous process and passed caudally as a single complex unit. Fibers
      progressively terminated over the four vertebral segments caudad, with multiple
      points of muscle fiber attachment on each vertebra. Motor endplates, defined with
      acetylcholinesterase histochemistry, were consistently located half way along
      each muscle fiber, regardless of length, with all muscle fibers arranged in
      parallel rather than in-series. These results provide information relevant to
      interpretation of developmental and functional studies involving this muscle
      group in the mouse and show mouse lumbar TSP muscles are different in form to
      descriptions of equivalent muscles in humans and horses.

PMID- 21082744
TI  - Predictable difficulty or difficulty to predict.

PMID- 21082745
TI  - Ab initio simulation of a 57-residue protein in explicit solvent reproduces the
      native conformation in the lowest free-energy cluster.
AB  - An enhanced conformational sampling method, multicanonical molecular dynamics
      (McMD), was applied to the ab intio folding of the 57-residue first repeat of
      human glutamyl- prolyl-tRNA synthetase (EPRS-R1) in explicit solvent. The
      simulation started from a fully extended structure of EPRS-R1 and did not utilize
      prior structural knowledge. A canonical ensemble, which is a conformational
      ensemble thermodynamically probable at an arbitrary temperature, was constructed
      by reweighting the sampled structures. Conformational clusters were obtained from
      the canonical ensemble at 300 K, and the largest cluster (i.e., the lowest free
      energy cluster), which contained 34% of the structures in the ensemble, was
      characterized by the highest similarity to the NMR structure relative to all
      alternative clusters. This lowest free-energy cluster included native-like
      structures composed of two anti-parallel alpha-helices. The canonical ensemble at
      300 K also showed that a short Gly-containing segment, which adopts an alpha
      helix in the native structure, has a tendency to be structurally disordered.
      Atomic-level analyses demonstrated clearly that inter-residue hydrophobic
      interactions drive the helix formation of the Gly-containing segment, and that
      increasing the hydrophobic contacts accompanies exclusion of water molecules from
      the vicinity of this segment. This study has shown, for the first time, that the
      free-energy landscape of a structurally well-ordered protein of about 60 residues
      is obtainable with an all atom model in explicit water without prior structural
      knowledge.

PMID- 21082746
TI  - Gene expression in the oropharynx of children exposed to secondhand smoke.
AB  - OBJECTIVES/HYPOTHESIS: To compare gene expression in oropharyngeal mucosa of
      children with (ex+) and without (ex-) secondhand smoke exposure. STUDY DESIGN:
      Prospective case-control. METHODS: Forty-one age- and gender-matched children (2
      6 years old) undergoing tonsillectomy for sleep disordered breathing at a
      tertiary care children's hospital were assessed for secondhand smoke exposure.
      Parental response to a validated questionnaire relating to secondhand smoke
      exposure governed inclusion. Sixteen samples were selected for microarray
      analysis (7 ex+, 9 ex-). Following tonsillectomy, ex vivo brushing of the mucosa
      isolated total RNA. Genome-wide expression profiles were generated by comparing
      sample RNA to a reference of all samples, assessing 27,323 cDNA clones.
      Microarray clones were ranked according to their ability to distinguish between
      the two groups using a Student t test. RESULTS: A total of 318 cDNA clones
      distinguished the two groups (P < .01); 180 genes were overexpressed and 138
      underexpressed in ex+ samples relative to the ex- group. Independent analysis of
      these two groups sorted genes into disease processes and molecular functional
      groups, including cancer (34 genes in the overexpressed group, 29 underexpressed,
      P < .05), cell cycle (14 and 10), and cell growth and proliferation (7 and 11).
      Two of the upregulated genes, LCN2 and IQGAP1, have been previously linked to
      inflammation in smokers and response/repair to cellular injury in bronchial
      epithelium. CONCLUSIONS: Findings in this pilot study support the hypothesis that
      secondhand smoke exposure seems to induce gene expression changes in the
      oropharyngeal mucosa of exposed children, which may have significant implications
      for current and future disease processes.

PMID- 21082747
TI  - Cochlear implantation in patients with autoimmune inner ear disease including
      cogan syndrome: a comparison with age- and sex-matched controls.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate the characteristics and outcomes of patients with
      autoimmune inner ear disease (AIED) who have undergone cochlear implantation (CI)
      and compare post-CI performance in AIED to matched controls. STUDY DESIGN:
      Retrospective case control study. METHODS: Study cohort was comprised of 25 adult
      implantees (AIED [n = 18], Cogan syndrome [n = 7]). The AIED group was defined by
      rapidly progressive bilateral sensorineural hearing loss leading to unusable
      hearing within weeks to months. Patients with Cogan syndrome, the archetypal
      inner ear autoimmune disease, were also examined and used for within-cohort
      comparison. Clinical and operative records were reviewed. Post-CI performance was
      assessed using open-set sentence tests. Age- and sex-matched individuals deafened
      by other postlingual causes were used as controls. RESULTS: Of 25 patients, 24
      had uneventful, full electrode insertions. One AIED patient had partial insertion
      due to cochlear ossification and did not achieve open-set speech perception post
      CI. Mean open-set sentence scores for study patients with uneventful insertions
      were 92.8%, 97.3%, and 96.4% at 6 months, 1 year, and >= 2 years, respectively.
      Compared to matched controls, patients deafened by autoimmune causes had
      significantly higher post-CI performance at all postoperative test intervals (P <
      .05). There was no significant difference in postimplantation performance between
      Cogan syndrome and AIED patients. CONCLUSIONS: To our knowledge this was the
      largest study of cochlear implantation in AIED and Cogan syndrome patients. In
      our experience, both groups generally attained high levels of post-CI speech
      perception and performed above average. Cochlear ossification affecting
      implantation in Cogan syndrome patients was not observed in our series, contrary
      to some reports.

PMID- 21082748
TI  - In-training assessment and predictors of competency in endoscopic sinus surgery.
AB  - OBJECTIVES: To evaluate the reliability and validity of the assessment tool for
      endoscopic sinus surgery when used in the operating room for in-training
      assessment of operative competency; to identify the tasks that may serve as the
      best indicators for overall surgical performance. STUDY DESIGN: Cross-sectional
      validation study. METHODS: We implemented the global and checklist parts of the
      endoscopic sinus surgery (ESS) assessment tool to evaluate the surgical skills of
      13 Otolaryngology-Head & Neck Surgery residents (PGY 1-5) in the operating room
      over a period of 15 months. Rhinology faculty scored residents' performance of
      every step of ESS at the end of each procedure using a previously validated tool.
      Construct validity was calculated by comparing scores across training levels
      (using analysis of variance [ANOVA]). Regression analysis was performed to
      identify tasks on the ESS checklist that most strongly correlated to the overall
      surgical performance. RESULTS: Construct validity was demonstrated with senior
      residents performing better than junior residents. Average checklist and global
      scores improved with the number of days on rhinology rotation. "Identification of
      uncinate and boundaries" was found to be the strongest predictor of overall
      surgical performance. CONCLUSIONS: The results indicate that this evaluation tool
      is a reliable and valid instrument for the assessment of surgical competency in
      the operating room. It can be used to identify weak areas of performance for
      which additional training may be required early in the rotation/training.

PMID- 21082763
TI  - The complete peptide dictionary--a meta-proteomics resource.
AB  - Recent developments in MS-based proteomics have increased the emphasis on
      peptides as a primary observable. While peptides are identified by tandem mass
      spectra, the link between peptide and protein remains implicit given the bottom
      up nature of the experiment in which proteins are enzymatically digested prior to
      sequencing. It is therefore useful to provide a fast lookup from peptide to
      protein in order to systematically establish the broadest possible protein basis
      for the observed peptides. Here, we describe Pep2Pro, a fast web-service
      providing protein lookup by peptides covering the entire protein space comprising
      ~10 million UniRef100 sequences. We demonstrate the usefulness of the service by
      reanalyzing peptides from two recent meta-proteomic data sets and identifying
      taxon-specific peptides, thereby implicating individual species as being present
      in these complex samples. The Pep2Pro web service can be accessed at
      http://www.pep2pro.org.

PMID- 21082764
TI  - p-Chlorobenzotrichloride revisited: novel analytical treatments of 2D exchange
      NQR in molecular crystals.
AB  - A theoretical treatment of the two-dimensional exchange nuclear quadrupole
      resonance pulse sequence is presented and applied to the quantitative study of
      exchange processes in molecular crystals. The theory is successfully tested for
      the exchange spectra of hindered trichloromethyl groups of p
      chlorobenzotrichloride, where the conventional approach without taking into
      account the off-resonance phenomena has failed. The mixing dynamics by exchange
      and the expected diagonal- and cross-peak intensities as a function of the mixing
      time have been derived. It is shown that the off-resonance effects are of crucial
      importance for the quantitative description of the exchange spectra.

PMID- 21082765
TI  - Fiber reduction and lipid enrichment in carotenoid-enriched distillers dried
      grain with solubles produced by secondary fermentation of Phaffia rhodozyma and
      Sporobolomyces roseus.
AB  - Carotenoid-enriched distillers dried grain with solubles (DDGS) developed as a
      value-added animal feed to provide carotenoids from mono and mixed culture (Mx)
      fermentation of red yeasts Phaffia rhodozyma (PR) and Sporobolomyces roseus (SR)
      were evaluated for their nutritional composition and compared to the control (C)
      DDGS. Apart from providing carotenoids, all three fermentation treatments reduced
      fiber with best reduction of 77% in PR, enhanced crude fat with highest of 81% in
      Mx, and reduced protein, amino acids and nitrogen by 50% in PR. DDGS fiber
      reduction by 77% was achieved by P. rhodozyma in the absence of any pretreatment.
      Qualitative and quantitative differences in fatty acid profiles were seen among
      the treatments. Vaccenic acid, a monounsaturated fatty acid produced in SR and Mx
      fermentation, was absent in C and PR. All these nutritional modifications are
      highly desirable in different DDGS-based animal feeds and can be explored to
      obtain tailor-made feeds/feed blends for specific animal diets.

PMID- 21082766
TI  - Discovery of novel GSK-3beta inhibitors with potent in vitro and in vivo
      activities and excellent brain permeability using combined ligand- and structure
      based virtual screening.
AB  - Dysregulation of glycogen synthase kinase (GSK-3beta) is implicated in the
      pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's,
      and others. A multistage virtual screening strategy designed so as to overcome
      known caveats arising from the considerable flexibility of GSK-3beta yielded,
      from among compounds in our in-house database and two commercial databases, new
      GSK-3beta inhibitors with novel scaffold structures. The two most potent and
      selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a
      phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity
      over CDK2 and were potent enough for direct in vivo validation. Both were able to
      cause significant increases in liver glycogen accumulation in dose-dependent
      fashion. One also exhibited excellent blood-brain barrier permeability, the other
      adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to
      experimentally corroborate or rule out ligand-bound structures arising from
      docking studies. SAR results supported one docking study among a number of
      alternatives.

PMID- 21082767
TI  - Metal nanoparticle wires formed by an integrated nanomolding-chemical assembly
      process: fabrication and properties.
AB  - We report here the use of nanomolding in capillaries (NAMIC) coupled with
      dithiocarbamate (DTC) chemistry to fabricate sub-50 nm quasi-1D arrays of 3.5 nm
      core gold nanoparticles (Au NPs) over large areas. Owing to chemical
      immobilization via the DTC bond, the patterned NP systems are stable in water and
      organic solvents, thus allowing the surface modification of the patterned Au NP
      arrays through thiol chemistry and further orthogonal binding of proteins. The
      electrical properties of these patterned Au NP wires have also been studied. Our
      results show that NAMIC combined with surface chemistry is a simple but powerful
      tool to create metal NP arrays that can potentially be applied to fabricate
      nanoelectronic or biosensing devices.

PMID- 21082768
TI  - Tuning the spin ground state in heterononanuclear nickel(II)-copper(II) cylinders
      with a triangular metallacyclophane core.
AB  - Two new heterometallic Ni(II)(n)Cu(II)((9-n)) complexes [n = 1 (2) and 2 (3)]
      have been synthesized following a multicomponent self-assembly process from a
      n:(3 - n):2:6 stoichiometric mixture of Ni(2+), Cu(2+), L(6-), and [CuL'](2+),
      where L and L' are the bridging and blocking ligands 1,3,5-benzenetris(oxamate)
      and N,N,N',N'',N''-pentamethyldiethylenetriamine, respectively. Complexes 2 and 3
      possess a unique cyclindrical architecture formed by three oxamato-bridged
      trinuclear linear units connected through two 1,3,5-substituted
      benzenetris(amidate) bridges, giving a triangular metallacyclophane core. They
      behave as a ferromagnetically coupled trimer of two (2)/one (3) S = (1)/(2)
      Cu(II)(3) plus one (2)/two (3) S = 0 Ni(II)Cu(II)(2) linear units with overall S
      = 1 Ni(II)Cu(II)(8) (2) and S = (1)/(2) Ni(II)(2)Cu(II)(7) (3) ground states.

PMID- 21082769
TI  - Theoretical study of 1,6-anhydrosugar formation from phenyl D-glucosides under
      basic condition: reasons for higher reactivity of beta-anomer.
AB  - Degradation of anomeric phenyl d-glucosides to levoglucosan under basic condition
      is theoretically studied. MP4(SDQ)//DFT(B3LYP)-computational results indicate
      that the degradation of phenyl alpha-glucoside (R(alpha)) occurs via the S(N)icB
      mechanism. In this mechanism, the oxyanion at the C6, which is formed through
      deprotonation of the OH group, directly attacks the anomeric carbon. On the other
      hand, the degradation of phenyl beta-glucoside (R(beta)) occurs via the
      S(N)icB(2) mechanism. In this mechanism, the oxyanion at the C2 attacks the
      anomeric carbon in a nucleophilic manner to afford 1,2-anhydride intermediate and
      then the oxyanion at the C6 attacks the anomeric carbon to afford levoglucosan.
      The activation barrier is much lower in the reaction of R(beta) (DeltaG(0++) =
      25.6 kcal/mol and E(a) = 26.5 kcal/mol) than in the reaction of R(alpha)
      (DeltaG(0++) = 38.1 kcal/mol and E(a) = 37.2 kcal/mol), which is consistent with
      the experimental observation that beta-glucoside is generally much more reactive
      than the corresponding alpha-glucoside. The lower activation barrier of the
      reaction of R(beta) arises from the stereoelectronic effect, which is induced by
      the charge transfer from the ring oxygen to the anomeric carbon, and the
      staggered conformation around the C1-C2 bond. When the stereoelectronic effect is
      absent, the degradation needs larger activation energy; for instance, the
      degradation of phenyl 5a-carba-beta-d-glucoside (R(Cbeta)) occurs with large
      DeltaG(0++) and E(a) values like those of alpha-glucosides, because the methylene
      group of R(Cbeta) does not contribute to the stereoelectronic effect. Also, the
      conformation around the C1-C2 bond is staggered in the transition state of the
      R(beta) reaction but eclipsed in that of the R(alpha) reaction, which also leads
      to the larger reactivity of R(beta).

PMID- 21082771
TI  - Rhodium(III)-catalyzed synthesis of isoquinolines from aryl ketone O-acyloxime
      derivatives and internal alkynes.
AB  - A synthetic method of isoquinolines from aryl ketone O-acyloxime derivatives and
      internal alkynes has been developed using [Cp*RhCl(2)](2)-NaOAc as the potential
      catalyst system. The present transformation is carried out by a redox-neutral
      sequence of C-H vinylation via ortho-rhodation and C-N bond formation of the
      putative vinyl rhodium intermediate on the oxime nitrogen, where the N-O bond of
      oxime derivatives could work as an internal oxidant to maintain the catalytic
      cycle.

PMID- 21082772
TI  - Hydroformylation of alkenylamines. Concise approaches toward piperidines,
      quinolizidines, and related alkaloids.
AB  - Linear hydroformylation of N-protected allyl- or homoallylamines
      (cyclohydrocarbonylation: CHC), followed by a reductive amination constitute the
      two key steps toward convenient routes to aza-heterocycles.

PMID- 21082773
TI  - One-step 18F-labeling of carbohydrate-conjugated octreotate-derivatives
      containing a silicon-fluoride-acceptor (SiFA): in vitro and in vivo evaluation as
      tumor imaging agents for positron emission tomography (PET).
AB  - The synthesis, radiolabeling, and initial evaluation of new silicon-fluoride
      acceptor (SiFA) derivatized octreotate derivatives is reported. So far, the main
      drawback of the SiFA technology for the synthesis of PET-radiotracers is the high
      lipophilicity of the resulting radiopharmaceutical. Consequently, we synthesized
      new SiFA-octreotate analogues derivatized with Fmoc-NH-PEG-COOH, Fmoc-Asn(Ac3AcNH
      beta-Glc)-OH, and SiFA-aldehyde (SIFA-A). The substances could be labeled in high
      yields (38 +/- 4%) and specific activities between 29 and 56 GBq/MUmol in short
      synthesis times of less than 30 min (e.o.b.). The in vitro evaluation of the
      synthesized conjugates displayed a sst2 receptor affinity (IC50 = 3.3 +/- 0.3 nM)
      comparable to that of somatostatin-28. As a measure of lipophilicity of the
      conjugates, the log P(ow) was determined and found to be 0.96 for SiFA-Asn(AcNH
      beta-Glc)-PEG-Tyr3-octreotate and 1.23 for SiFA-Asn(AcNH-beta-Glc)-Tyr3
      octreotate, which is considerably lower than for SiFA-Tyr3-octreotate (log P(ow)
      = 1.59). The initial in vivo evaluation of [18F]SiFA-Asn(AcNH-beta-Glc)-PEG-Tyr3
      octreotate revealed a significant uptake of radiotracer in the tumor tissue of
      AR42J tumor-bearing nude mice of 7.7% ID/g tissue weight. These results show that
      the high lipophilicity of the SiFA moiety can be compensated by applying
      hydrophilic moieties. Using this approach, a tumor-affine SiFA-containing peptide
      could successfully be used for receptor imaging for the first time in this proof
      of concept study.

PMID- 21082774
TI  - Antitumor agents 286. Design, synthesis, and structure-activity relationships of
      3'R,4'R-disubstituted-2',2'-dimethyldihydropyrano[2,3-f]chromone (DSP) analogues
      as potent chemosensitizers to overcome multidrug resistance.
AB  - In this study, various 3'R,4'R-disubstituted-2',2'-dimethydihydropyrano[2,3
      f]chromone (DSP) derivatives were discovered as potent chemosensitizers in the
      treatment of multidrug resistant cancer cells. Twenty-four DSP analogues (5-28)
      were synthesized and evaluated against a multidrug resistant (MDR) cell line (KB
      Vin) with and without vincristine (VCR). All DSP analogues exhibited low
      intrinsic cytotoxicity. However, in combination treatment, most DSPs reversed
      resistance to VCR and lowered the GI50 value of VCR by 12-349-fold. At a
      concentration of 1 MUg/mL, three compounds, 11, 14, and 21, fully reversed
      resistance to VCR in KB-Vin cancer cells, a 2-fold increase compared to
      verapamil, a first-generation chemosensitizer. Detailed structure-activity
      relationship (SAR) conclusions were established based on 3' and 4' substitutions.
      Moreover, a preliminary mechanism study indicated that the chemosensitizing
      activity of DSP analogues results from inhibition of P-glycoprotein (P-gp)
      overexpressed in MDR cancer cells.

PMID- 21082775
TI  - Discriminating and imaging different phosphatidylcholine species within phase
      separated model membranes by principal component analysis of TOF-secondary ion
      mass spectrometry images.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) enables chemically
      imaging the distributions of various lipid species in model membranes. However,
      discriminating the TOF-SIMS data of structurally similar lipids is very difficult
      because the high intensity, low mass fragment ions needed to achieve
      submicrometer lateral resolution are common to multiple lipid species. Here, we
      demonstrate that principal component analysis (PCA) can discriminate the TOF-SIMS
      spectra of four unlabeled saturated phosphatidylcholine species, 1,2-dilauroyl-sn
      glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn
      glycero-3-phosphocholine (DSPC) according to variations in the intensities of
      their low mass fragment ions (m/z <= 200). PCA of TOF-SIMS images of phase
      separated DSPC/DLPC and DPPC/DLPC membranes enabled visualizing the distributions
      of each phosphatidylcholine species with higher contrast and specificity than
      that of individual TOF-SIMS ion images. Comparison of the principal component
      (PC) scores images to atomic force microscopy (AFM) images acquired at the same
      membrane location before TOF-SIMS analysis confirmed that the PC scores images
      reveal the phase-separated membrane domains. The lipid composition within these
      domains was identified by projection of their TOF-SIMS spectra onto PC models
      developed using pure lipid standards. This approach may enable the identification
      and chemical imaging of structurally similar lipid species within more complex
      membranes.

PMID- 21082776
TI  - The proline/arginine-rich domain is a major determinant of dynamin self
      activation.
AB  - Dynamins induce membrane vesiculation during endocytosis and Golgi budding in a
      process that requires assembly-dependent GTPase activation. Brain-specific
      dynamin 1 has a weaker propensity to self-assemble and self-activate than
      ubiquitously expressed dynamin 2. Here we show that dynamin 3, which has
      important functions in neuronal synapses, shares the self-assembly and GTPase
      activation characteristics of dynamin 2. Analysis of dynamin hybrids and of
      dynamin 1-dynamin 2 and dynamin 1-dynamin 3 heteropolymers reveals that
      concentration-dependent GTPase activation is suppressed by the C-terminal
      proline/arginine-rich domain of dynamin 1. Dynamin proline/arginine-rich domains
      also mediate interactions with SH3 domain-containing proteins and thus regulate
      both self-association and heteroassociation of dynamins.

PMID- 21082777
TI  - Sensitive carbohydrate detection using surface enhanced Raman tagging.
AB  - Glycomic analysis is an increasingly important field in biological and biomedical
      research as glycosylation is one of the most important protein post-translational
      modifications. We have developed a new technique to detect carbohydrates using
      surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine
      B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine
      based tag (RT) was successfully conjugated to three model carbohydrates (glucose,
      lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe
      laser were ~1 nM in concentration for all the RT-carbohydrate conjugates and ~10
      fmol in total sample consumption. The dynamic range of the SERS method is about 4
      orders of magnitude, spanning from 1 nM to 5 MUM. Ratiometric SERS quantification
      using isotope-substituted SERS internal references allows comparative
      quantifications of carbohydrates labeled with RT and deuterium/hydrogen
      substituted RT tags, respectively. In addition to enhancing the SERS detection of
      the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass
      spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT
      carbohydrates is ~3 nM in concentration while the mass spectrometry (MS)
      sensitivity is about 1 fmol, achieved with a linear ion trap electrospray
      ionization (ESI)-MS instrument. Potential applications that take advantage of the
      high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are
      discussed for practical glycomic analysis where carbohydrates may be quantified
      with a fluorescence and SERS technique and then identified with ESI-MS
      techniques.

PMID- 21082778
TI  - Biochemical and physiological characterization of a BLUF protein-EAL protein
      complex involved in blue light-dependent degradation of cyclic diguanylate in the
      purple bacterium Rhodopseudomonas palustris.
AB  - Organisms adapt their physiologies in response to the quality and quantity of
      environmental light. Members of a recently identified photoreceptor protein
      family, BLUF domain proteins, use a flavin chromophore to sense blue light.
      Herein, we report that PapB, which contains a BLUF domain, controls the biofilm
      formation of the purple photosynthetic bacterium Rhodopseudomonas palustris.
      Purified PapB undergoes a typical BLUF-type photocycle, and light-excited PapB
      enhances the phosphodiesterase activity of the EAL domain protein, PapA, which
      degrades the second messenger, cyclic dimeric GMP (c-di-GMP). PapB directly
      interacts with PapA in vitro in a light-independent manner and induces a
      conformational change in the preformed PapA-PapB complex. A PapA-PapB docking
      simulation, as well as a site-directed mutagenesis study, identified amino acids
      partially responsible for the interaction between the PapA EAL domain and the two
      C-terminal alpha-helices of the PapB BLUF domain. Thus, the conformational
      change, which involves the C-terminal alpha-helices, transfers the flavin-sensed
      blue light signal to PapA. Deletion of papB in R. palustris enhances biofilm
      formation under high-intensity blue light conditions, indicating that PapB
      functions as a blue light sensor, which negatively regulates biofilm formation.
      These results demonstrate that R. palustris can control biofilm formation via a
      blue light-dependent modulation of its c-di-GMP level by the BLUF domain protein,
      PapB.

PMID- 21082779
TI  - Electron paramagnetic resonance investigation of purified catalyst-free single
      walled carbon nanotubes.
AB  - Electron paramagnetic resonance of single-walled carbon nanotubes (SWCNTs) has
      been bedevilled by the presence of paramagnetic impurities. To address this,
      SWCNTs produced by laser ablation with a nonmagnetic PtRhRe catalyst were
      purified through a multiple step centrifugation process in order to remove
      amorphous carbon and catalyst impurities. Centrifugation of a SWCNT solution
      resulted in sedimentation of carbon nanotube bundles containing clusters of
      catalyst particles, while isolated nanotubes with reduced catalyst particle
      content remained in the supernatant. Further ultracentrifugation resulted in
      highly purified SWCNT samples with a narrow diameter distribution and almost no
      detectable catalyst particles. Electron paramagnetic resonance (EPR) signals were
      detected only for samples which contained catalyst particles, with the
      ultracentrifuged SWCNTs showing no EPR signal at X-band (9.4 GHz) and fields <
      0.4 T.

PMID- 21082781
TI  - Chromogenic and fluorogenic signaling of sulfite by selective deprotection of
      resorufin levulinate.
AB  - A new sulfite-selective probe system based on resorufin was investigated.
      Levulinate of resorufin exhibited a prominent chromogenic and turn-on type
      fluorogenic signaling toward sulfite ions in aqueous media based on the selective
      deprotection of the levulinate group. The sulfite-selective signaling was
      possible in the presence of commonly encountered anions.

PMID- 21082782
TI  - Efficient synthesis of 5-hydroxymethylcytosine containing DNA.
AB  - 5-Hydroxymethylcytosine ((5-HOMe)dC) was recently discovered as the sixth base in
      the mammalian genome. The development of a new phosphoramidite building block is
      reported, which allows efficient synthesis of (5-HOMe)dC containing DNA. Key
      steps of the synthesis are a palladium-catalyzed formylation and the simultaneous
      protection of a hydroxyl and amino group as a cyclic carbamate. DNA synthesis is
      possible under standard conditions, and deprotection can be carried out with
      dilute NaOH.

PMID- 21082780
TI  - Cytochrome P450 from Photobacterium profundum SS9, a piezophilic bacterium,
      exhibits a tightened control of water access to the active site.
AB  - We report cloning, expression in Escherichia coli, and purification of cytochrome
      P450 from a deep-sea bacterium Photobacterium profundum strain SS9 (P450-SS9).
      The enzyme, which is predominately high spin (86%) in the absence of any added
      ligand, binds fatty acids and their derivatives and exhibits the highest affinity
      for myristic acid. Binding of the majority of saturated fatty acids displaces the
      spin equilibrium further toward the high-spin state, whereas the interactions
      with unsaturated fatty acids and their derivatives (arachidonoylglycine) have the
      opposite effect. Pressure perturbation studies showed that increasing pressure
      fails to displace the spin equilibrium completely to the low-spin state in the
      ligand-free P450-SS9 or in the complexes with either myristic acid or
      arachidonoylglycine. Stabilization of high-spin P450-SS9 signifies a pressure
      induced transition to a state with reduced accessibility of the active site. This
      transition, which is apparently associated with substantial hydration of the
      protein, is characterized by the reaction volume change (DeltaV) around -100 to 
      200 mL/mol and P(1/2) of 300-800 bar, which is close to the pressure of
      habitation of P. profundum. The transition to a state with confined water
      accessibility is hypothesized to represent a common feature of cytochromes P450
      that serves to coordinate heme pocket hydration with ligand binding and the redox
      state. Displacement of the conformational equilibrium toward the "closed" state
      in P450-SS9 (even ligand-free) may have evolved to allow the protein to adapt to
      enhanced protein hydration at high hydrostatic pressures.

PMID- 21082783
TI  - Total syntheses of the marine illudalanes alcyopterosin I, L, M, N, and C.
AB  - The combination of a modular assembly of enantiopure triynes and a powerful
      rhodium-catalyzed [2 + 2 + 2] alkyne cyclotrimerization reaction opens new and
      efficient entries to a set of alcyopterosins, including the first total synthesis
      of the alcyopterosins L, M, and C.

PMID- 21082784
TI  - Expeditious synthesis of phenanthridines from benzylamines via dual palladium
      catalysis.
AB  - A method for the synthesis of phenanthridines from benzylamines and aryl iodides
      which uses a dual palladium-catalyzed process is developed. The domino sequence
      ends via an intramolecular amination and an oxidative dehydrogenation. No
      protecting group or prefunctionalization of the amine is required, and the
      process uses dioxygen as the terminal oxidant.

PMID- 21082785
TI  - Sequence-specific recognition of DNA oligomer using peptide nucleic acid (PNA)
      modified synthetic ion channels: PNA/DNA hybridization in nanoconfined
      environment.
AB  - Here we demonstrate the design and construction of a simple, highly sensitive and
      selective nanofluidic sensing device, based on a single synthetic conical
      nanochannel for the sequence specific detection of single-stranded DNA
      oligonucleotides. The biosensing performance of the device depends sensitively on
      the surface charge and chemical groups incorporated on the inner channel wall
      that act as binding sites for different analytes. Uncharged peptide nucleic acid
      (PNA) probes are covalently immobilized on the channel surface through
      carbodiimide coupling chemistry. This diminishes the channel surface charge,
      leading to a significant decrease in the rectified ion current flowing through
      the channel. The PNA-modified channel acts as a highly specific and selective
      device for the detection of a complementary single-stranded DNA sequence. Upon
      PNA/DNA hybridization, the channel surface charge density increased due to the
      presence of the negatively charged DNA strand. The changes in the surface charge
      dependent current-voltage (I-V) curves and rectification ratio of the channel
      confirm the success of immobilization and PNA/DNA hybridization within a confined
      space at the nanoscale. In addition, a control experiment indicated that the
      biosensor exhibits remarkable specificity toward a cDNA strand and also has the
      ability to discriminate single-base mismatch DNA sequences on the basis of
      rectified ion flux through the nanochannel. In this context, we envision that the
      single conical nanochannels functionalized with a PNA probe will provide a
      biosensing platform for the detection and discrimination of short single-stranded
      DNA oligomer of unknown sequence.

PMID- 21082786
TI  - In situ growth of catalytic active Au-Pt bimetallic nanorods in thermoresponsive
      core-shell microgels.
AB  - Here, we demonstrate that bimetallic Au-Pt nanorods (NRs) can be grown in situ
      into thermosensitive core-shell microgel particles by a novel two-step approach.
      In the first step, Au NRs with an average width of 6.6 +/- 0.3 nm and length of
      34.5 +/- 5.2 nm (aspect ratio 5.2 +/- 0.6) were homogeneously embedded into the
      shell of PNIPA networks. The volume transition of the microgel network leads to a
      strong red shift of the longitudinal plasmon band of the Au NRs. In the second
      step, platinum was preferentially deposited onto the tips of Au NRs to form
      dumbbell-shaped bimetallic nanoparticles. The novel synthesis forms bimetallic Au
      Pt NRs immobilized in microgels without impeding their colloidal stability.
      Quantitative analysis of the catalytic activity for the reduction of 4
      nitrophenol indicates that bimetallic Au-Pt NRs show highly enhanced catalytic
      activity, which is due to the synergistic effect of bimetallic nanoparticles. The
      catalytic activity of immobilized Au-Pt NRs can be modulated by the volume
      transition of thermosensitive microgels. This demonstrates that core-shell
      microgels are capable of serving as "smart nanoreactors" for the catalytic active
      bimetallic nanoparticles with controlled morphology and high colloidal stability.

PMID- 21082787
TI  - SPINOL-derived phosphoric acids: synthesis and application in enantioselective
      Friedel-Crafts reaction of indoles with imines.
AB  - A new class of chiral phosphoric acids with spirobiindane as scaffold were
      conveniently synthesized from (S)-1,1'-spirobiindane-7,7'-diol ((S)-SPINOL) and
      employed to catalyze the asymmetric Friedel-Crafts reaction of indoles with
      imines to afford 3-indolyl methanamines. High yields (68-97%) and excellent
      enantioselectivities (up to 99% ee) were obtained.

PMID- 21082788
TI  - Reversible and controllable nanolocomotion of an RNA-processing machinery.
AB  - Molecular motors have inspired many avenues of research for nanotechnology but
      most molecular motors studied so far allow only unidirectional movement. The
      archaeal RNA-exosome is a reversible motor that can either polymerize or degrade
      an RNA strand, depending on the chemical environments. We developed a single
      molecule fluorescence assay to analyze the real time locomotion of this
      nanomachine on RNA. Despite the multimeric structure, the enzyme followed the
      Michaelis-Menten kinetics with the maximum speed of ~3 nucleotides/s, showing
      that the three catalytic cylinders do not fire cooperatively. We also demonstrate
      rapid directional switching on demand by fluidic control. When the two reaction
      speeds are balanced on average, the enzyme shows a memory of the previous
      reaction it catalyzed and stochastically switches between primarily polymerizing
      and primarily degrading behaviors. The processive, reversible, and controllable
      locomotion propelled by this nanomachine has a promising potential in
      environmental sensing, diagnostic, and cargo delivery applications.

PMID- 21082789
TI  - Characterization of self-association and heteroassociation of bacterial cell
      division proteins FtsZ and ZipA in solution by composition gradient-static light
      scattering.
AB  - We have characterized the self-association of FtsZ in its GDP-bound state (GDP
      FtsZ) and the heteroassociation of FtsZ and a soluble recombinant ZipA (sZipA)
      lacking the N-terminal transmembrane domain by means of composition gradient
      static light scattering (CG-SLS) and by measurement of sedimentation equilibrium.
      CG-SLS experiments at high ionic strengths and in the presence of 5 mM Mg(2+)
      show that, while FtsZ self-associates in a noncooperative fashion, sZipA acts as
      a monomer. CG-SLS data obtained from mixtures of FtsZ (A) and sZipA (B) in the
      presence of Mg(2+) are quantitatively described by an equilibrium model that
      takes into account significant scattering contributions from B, A(1), A(2), A(3),
      A(4), A(5), A(6), A(1)B, A(2)B, A(3)B, and A(4)B. However, in the absence of
      Mg(2+) (with EDTA), the data are best explained by an equilibrium model in which
      only B, A(1), A(2), A(3), A(1)B, and A(2)B contribute significantly to
      scattering. The best-fit molecular weights of monomeric A and B are in good
      agreement with values calculated from amino acid composition and with values
      obtained from sedimentation equilibrium. The latter technique also confirmed the
      interaction between sZipA and GDP-FtsZ. Moreover, the association model that best
      describes the CG-SLS data is in qualitative agreement with the sedimentation
      data. From these results, it follows that the binding of sZipA to GDP-FtsZ is of
      moderate affinity and does not significantly affect the interactions between FtsZ
      monomers. Under the working conditions used, only one sZipA binds to FtsZ
      oligomers with a length of six at most. The observed behavior would be compatible
      with FtsZ fibrils being anchored in vivo to the bacterial inner plasma membrane
      by substoichiometric binding of membrane-bound ZipA.

PMID- 21082790
TI  - Synthesis of beta-keto esters in-flow and rapid access to substituted
      pyrimidines.
AB  - We have developed an in-flow process for the synthesis of beta-keto esters via
      the BF(3).OEt(2)-catalyzed formal C-H insertion of ethyl diazoacetate into
      aldehydes. The beta-keto esters were then condensed with a range of amidines to
      give a variety of 2,6-substituted pyrimidin-4-ols.

PMID- 21082791
TI  - A Q63E Rhodobacter sphaeroides AppA BLUF domain mutant is locked in a pseudo
      light-excited signaling state.
AB  - The AppA BLUF photoreceptor from Rhodobacter sphaeroides contains a conserved key
      residue, Gln63, that is thought to undergo a shift in hydrogen-bonding
      interactions when a bound flavin is light excited. In this study we have
      characterized two substitution mutants of Gln63 (Q63E, Q63L) in the context of
      two constructs of the BLUF domain that have differing lengths, AppA1-126 and
      AppA17-133. Q63L mutations in both constructs exhibit a blue-shifted flavin
      absorption spectrum as well as a loss of the photocycle. Altered fluorescence
      emission and fluorescence quenching of the Q63L mutant indicate significant
      perturbations of hydrogen bonding to the flavin and surrounding amino acids which
      is confirmed by (1)H-(15)N HSQC NMR spectroscopy. The Q63E substitution mutant is
      constitutively locked in a lit signaling state as evidenced by a permanent 3 nm
      red shift of the flavin absorption, quenching of flavin fluorescence emission,
      analysis of (1)H-(15)N HSQC spectra, and the inability of full-length AppA Q63E
      to bind to the PpsR repressor. The significance of these findings on the
      mechanism of light-induced output signaling is discussed.

PMID- 21082792
TI  - Chemistry of the oxophosphinidene ligand. 2. Reactivity of the anionic complexes
      [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) toward
      electrophiles based on elements different from carbon.
AB  - The anionic oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] (M = Mo, W; R*
      = 2,4,6-C(6)H(2)(t)Bu(3); Cp = eta(5)-C(5)H(5), DBU = 1,8-diazabicyclo [5.4.0]
      undec-7-ene) displayed multisite reactivity when faced with different
      electrophilic reagents. The reactions with the group 14 organochloride compounds
      ER(4-x)Cl(x) (E = Si, Ge, Sn, Pb) led to either phosphide-like, oxophosphinidene
      bridged derivatives [MCp{P(OE')R*}(CO)(2)] (E' = SiMe(3), SiPh(3), GePh(3),
      GeMe(2)Cl) or to terminal oxophosphinidene complexes [MCp{P(O)R*}(CO)(2)(E')] (E'
      = SnPh(3), SnPh(2)Cl, PbPh(3); Mo-Pb = 2.8845(4) A for the MoPb compound). A
      particular situation was found in the reaction with SnMe(3)Cl, this giving a
      product existing in both tautomeric forms, with the phosphide-like complex
      [MCp{P(OSnMe(3))R*}(CO)(2)] prevailing at room temperature and the tautomer
      [MCp{P(O)R*}(CO)(2)(SnMe(3))] being the unique species present below 203 K in
      dichloromethane solution. The title anions also showed a multisite behavior when
      reacting with transition-metal based electrophiles. Thus, the reactions with the
      complexes [M'Cp(2)Cl(2)] (M' = Ti, Zr) gave phosphide-like derivatives
      [MCp{P(OM')R*}(CO)(2)] (M = Mo, M' = TiCp(2)Cl, ZrCp(2)Cl; M = W, M' =
      ZrCp(2)Cl), displaying a bridging kappa(1),kappa(1)-P,O- oxophosphinidene ligand
      connecting MCp(CO)(2) and M'Cp(2)Cl metal fragments (W-P = 2.233(1) A, O-Zr =
      2.016(4) A for the WZr compound]. In contrast, the reactions with the complex
      [AuCl{P(p-tol)(3)}] gave the metal-metal bonded derivatives trans
      [MCp{P(O)R*}(CO)(2){AuP(p-tol)(3)}] (M = Mo, W; Mo-Au = 2.7071(7) A). From all
      the above results it was concluded that the terminal oxophosphinidene complexes
      are preferentially formed under conditions of orbital control, while charge
      controlled reactions tend to give derivatives with the electrophilic fragment
      bound to the oxygen atom of the oxophosphinidene ligand (phosphide-like,
      oxophosphinidene-bridged derivatives).

PMID- 21082793
TI  - Divergent route to access structurally diverse 4-quinolones via mono or
      sequential cross-couplings.
AB  - A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)
      quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura
      cross-coupling to generate novel and medicinally important 4(1H)-quinolones.
      Copper- and palladium-catalyzed cyanations were used to functionalize the 4
      quinolone core further.

PMID- 21082794
TI  - Unconventional salt trend from soft to stiff in single neurofilament biopolymers.
AB  - We present persistence length measurements on neurofilaments (NFs), an
      intermediate filament with protruding side arms, of the neuronal cytoskeleton.
      Tapping mode atomic force microscopy enabled us to visualize and trace at
      subpixel resolution photoimmobilized NFs, assembled at various subunit protein
      ratios, thereby modifying the side-arm length and chain density charge
      distribution. We show that specific polyampholyte sequences of the side arms can
      form salt-switchable intrafilament attractions that compete with the net
      electrostatic and steric repulsion and can reduce the total persistence length by
      half. The results are in agreement with present X-ray and microscopy data yet
      present a theoretical challenge for polyampholyte interchain interactions.

PMID- 21082795
TI  - Polymerization of electric field-centered double emulsion droplets to create
      polyacrylate shells.
AB  - Porous and hollow particles are widely used in pharmaceuticals, as solid phases
      for chromatography, as catalyst supports, in bioanalytical assays and medical
      diagnostics, and in many other applications. By controlling size, shape, and
      chemistry, it is possible to tune the physical and chemical properties of the
      particles. In some applications of millimeter-scale hollow shells, such as in
      high energy density physics, controlling the shell thickness uniformity
      (concentricity) and roundness (sphericity) becomes particularly important. In
      this work, we demonstrate the feasibility of using electric field-driven droplet
      centering to form highly spherical and concentric polymerizable double emulsion
      (DE) droplets that can be subsequently photopolymerized into polymer shells.
      Specifically, when placed under the influence of an ~6 * 10(4) V(rms)/m field at
      20 MHz, DE droplets, consisting of silicone oil as the inner droplet and
      tripropylene glycol diacrylate with a photoinitiator in N,N-dimethylacetamide as
      the outer droplet, suspended in ambient silicone oil, were found to undergo
      electric field-driven centering into droplets with >=98% sphericity and ~98%
      concentricity. The centered DE droplets were photopolymerized in the presence of
      the electric field. The high degrees of sphericity and concentricity were
      maintained in the polymerized particles. The poly(propylene glycol diacrylate)
      capsules are just within the sphericity requirements needed for inertial
      confinement fusion experiments. They were slightly outside the concentricity
      requirement. These results suggest that electric field-driven centering and
      polymerization of double emulsions could be very useful for synthesizing hollow
      polymer particles for applications in high energy density physics experiments and
      other applications of concentric polymer shells.

PMID- 21082796
TI  - Electrogravimetric real-time and in situ michaelis-menten enzymatic kinetics:
      progress curve of acetylcholinesterase hydrolysis.
AB  - A piezoelectric detection of enzyme-modified surface was performed under
      Michaelis-Menten presumptions of steady-state condition. The approach herein
      presented showed promise in the study of enzymatic kinetics by measuring the
      frequency changes associated with mass changes at the piezoelectric crystal
      surface. Likewise, real-time frequency shifts, that is, dDeltaf/dt, indicated the
      rate of products formation from enzymatic reaction. In this paper,
      acetylcholinesterase was used as the enzymatic model and acetylcholine as
      substrate. The enzymatic rate has its maximum value for a short time during the
      kinetic reaction, for instance, during the first ten minutes of the reaction time
      scale. The values found for the kinetic constant rate and Michaelis-Menten
      constant were (1.4 +/- 0.8) 10(5) s(-1) and (5.2 +/- 3) 10(-4) M, respectively,
      in agreement with the values found in classical Michaelis-Menten kinetic
      experiments.

PMID- 21082797
TI  - A simultaneous study of kinetics and thermodynamics of anion transfer across the
      liquid/liquid interface by means of Fourier transformed large-amplitude square
      wave voltammetry at three-phase electrode.
AB  - This paper describes a novel application of Fourier transformed large-amplitude
      square-wave voltammetry (FT-SWV) in combination with three-phase edge plane
      pyrolytic graphite (EPPG) electrode to investigate both the kinetics and
      thermodynamics of anion transfer across the liquid/liquid interface using a
      conventional three-electrode arrangement. The transfer of anion from aqueous
      phase to organic phase was electrochemically driven by reversible redox
      transformation of confined redox probe in the organic phase. The kinetics and
      thermodynamics of anion transfer were inspected by a so-called "quasi-reversible
      maximum" (QRM) emerged in the profile of even harmonic components of power
      spectrum obtained by Fourier transformation (FT) of time-domain total current
      response and formal potential E(f) of first harmonic voltammogram obtained by
      application of inverse FT on the power spectrum. Besides, a systematic study of
      patterns of behavior of a variety of anions at the same concentration and a
      specific anion at different concentrations on kinetics and thermodynamics and the
      effect of amplitude DeltaE on QRM were also conducted, aiming to optimize the
      measurement conditions. The investigation mentioned above testified that the ion
      transfer across the liquid/liquid interface controls the kinetics of overall
      electrochemical process, regardless of either FT-SWV or traditional SWV
      investigation. Moreover, either the kinetic probe f(max) or the thermodynamic
      probe E(f) can be served as a way for analytical applications. Interestingly, a
      linear relationship between peak currents of the first harmonic components and
      concentrations of perchlorate anion in the aqueous solutions can be observed,
      which is somewhat in accordance with a finding obtained by Fourier transformed
      alternating current voltammetry (FT-ACV) [Bond, A. M.; Duffy, N. W.; Elton, D.
      M.; Fleming, B. D. Anal. Chem. 2009, 81, 8801-8808]. This may open a new door for
      analytical detection of a wide spectrum of electrochemically inactive analytes of
      biological and environmental significance. Compared with traditional SWV, FT-SWV
      is much simpler and faster in ion transfer kinetics estimation and also provides
      a new access to thermodynamics evaluation.

PMID- 21082798
TI  - Films of lutetium bisphthalocyanine nanowires as electrochemical sensors.
AB  - Lutetium bisphthalocyanine (LuPc(2)) nanowires have been successfully obtained by
      electrophoretic deposition (EPD). The influence of the deposition conditions and
      annealing in the structure of the films has been studied by AFM, SEM, X-ray
      diffraction (XRD), UV-vis absorption, and near-infrared (NIR). The
      electrochemical properties of the EDP films immersed in different electrolytic
      solutions (KCl, MgCl(2), KClO(4), HCl, and NaOH) indicate that anions diffuse
      inside the film to maintain the electroneutrality and the kinetics follows the
      Randles-Sevcik equation. The stability of the response increases strongly upon
      annealing due to the improvement of the adhesion of the sensitive material to the
      substrate. The EPD films have been successfully used to detect caffeic acid (an
      antioxidant of interest in the food industry). The anodic peak associated with
      the oxidation of caffeic acid appears at 0.54 V and is linearly dependent on the
      caffeic acid concentration in the 6 * 10(-5) M to 5 * 10(-4) M range with a
      detection limit of 3.12 * 10(-5) M. The electrochemical behavior of the annealed
      LuPc(2) EPD films is similar to that observed using Langmuir-Blodgett (LB)
      nanostructured films. However, the different molecular organization of the
      molecules inside the film causes differences in the shape and position of the
      peaks. Although LuPc(2) sensors prepared with both EPD and LB techniques provide
      stable and reproducible responses, the use of EPD is preferred for real sensing
      applications because of its lower cost, shorter preparation time, and longer
      lifetime.

PMID- 21082799
TI  - Ultrafast manipulation of strong coupling in metal-molecular aggregate hybrid
      nanostructures.
AB  - We demonstrate an ultrafast manipulation of the Rabi splitting energy Omega(R) in
      a metal-molecular aggregate hybrid nanostructure. Femtosecond excitation
      drastically alters the optical properties of a model system formed by coating a
      gold nanoslit array with a thin J-aggregated dye layer. Controlled and reversible
      transient switching from strong (Omega(R) ? 55 meV) to weak (Omega(R) ~ 0)
      coupling on a sub-ps time scale is directly evidenced by mapping the
      nonequilibrium dispersion relations of the coupled excitations. Such a strong,
      externally controllable coupling of excitons and surface plasmon polaritons is of
      considerable interest for ultrafast all-optical switching applications in
      nanoscale plasmonic circuits.

PMID- 21082800
TI  - Nanostructured aniline oxidation products: self-assembled films at the air/liquid
      interface.
AB  - With the use of the "falling pH" approach, the free floating films obtained at
      the air/liquid interface during aniline oxidative polymerization in the presence
      of hydrochloric acid have been reported and characterized for the first time. The
      surface of the films is compact and consists of small densely packed particles
      (around 10-20 nm in diameter). In addition to the free floating films the
      precipitation of various self-assembled nanostructures was also observed. The
      thickness of the films depends on the concentration of the reactants and ranges
      from 40 to 50 nm. Scanning electron microscopy (SEM) and transmission electron
      microscopy results imply that 3D nanostructures are physically adsorbed onto the
      film and that they represent two separated phases. Fourier transform infrared
      (FTIR) and UV-vis measurements have confirmed the presence of polyaniline and
      branched oligoanilines. On the basis of an orientation distribution of H(2)O and
      aniline molecules at the air/liquid interface and with the use of the cooperative
      effect of hydrogen-bond formation, a mechanism for film growth has been proposed.
      Three samples are synthesized in the presence of different acids-nitric,
      sulfuric, and acetic. The SEM and FTIR data showed similar morphologies and
      structural characteristics. This implies that the morphology and structure of the
      final products depend on the acidity conditions (pH) during the reaction rather
      than on the nature of the dopant acid.

PMID- 21082801
TI  - Wettability of a quartz surface in the presence of four cationic surfactants.
AB  - Advancing contact angle (theta) measurements were carried out for aqueous
      solutions of four cationic surfactants, hexadecanol glycidyl ether ammonium
      chloride (C(16)PC), guerbet alcohol hexadecyl glycidyl ether ammonium chloride
      (C(16)GPC), hexadecanol polyoxyethylene(3) glycidyl ether ammonium chloride
      (C(16)(EO)(3)PC), and guerbet alcohol hexadecyl polyoxyethylene(3) glycidyl ether
      ammonium chloride (C(16)G(EO)(3)PC), on the quartz surface using the sessile drop
      analysis. The influences of surfactant type and bulk concentration on contact
      angle were expounded, and the changes in adhesional tension and adhesion work
      were discussed. The contact angle increases up to a maximum with the increasing
      concentration for all cationic surfactants. Surfactants with branched chain have
      more hydrophobic group density on the quartz surface, which results in higher
      values of maxima in contact angle curves. When ethylene oxide groups CH(2)CH(2)O
      were incorporated in the hydrophobic group, the decrease in contact angle maximum
      was observed for C(16)(EO)(3)PC and C(16)G(EO)(3)PC. Moreover, an increase in
      quartz-water interfacial free energy (gamma(SL)) has been observed due to the
      adsorption of four cationic surfactants. The four cationic surfactants can form a
      monolayer with alignment structure on the quartz surface through electrostatic
      interaction and then form the bilayer with increasing bulk concentration. In
      contrast with literature, the maximal contact angles may not necessarily
      correspond to the beginning of the formation of bilayer for cationic surfactants
      at the quartz-water interface. Moreover, the concentrations corresponding to
      maximal contact angles for C(16)PC and C(16)(EO)(3)PC were much lower than their
      CMC. The contact angle passes through a maximum at a concentration obviously
      higher than CMC for C(16)G(EO)(3)PC.

PMID- 21082803
TI  - A gallium-catalyzed cycloisomerization/Friedel-Crafts tandem.
AB  - Under noble (Au, Pt, Ru) and group 13 (Ga, In) metals catalysis, 1,6-arenynes
      rearrange to give 1,2-dihydronaphthalenes in a high yielding, regiocontrolled
      fashion. When the reaction is carried out in the presence of electron-rich arenes
      (anisole, phenol, indole derivatives), Friedel-Crafts addition may follow the
      cycloisomerization step. Only GaX(3) salts proved able to catalyze these two C-C
      bond formation events. This specificity of gallium has been exploited for the
      synthesis of valuable polycyclic compounds that would be very difficult to
      prepare otherwise. For instance, tetrahydroisoquinolines and
      tetrahydrobenzoazepines have been obtained by selective 6-exo-dig or 7-endo-dig
      cyclization of N-tethered 1,6-arenynes. DFT calculations were carried out to shed
      light on the mechanism and provide a rationale for this regiodivergency.
      Computations also reveal the fundamental role of the tether in the stabilization
      of carbocationic species. Differential reactivities of other types of substrates
      in gallium- and gold-catalyzed cascades are also exposed, showing that the two
      approaches are complementary. In particular, bimolecular Friedel-Crafts additions
      are facilitated under gallium catalysis.

PMID- 21082802
TI  - Bioactivity-guided isolation of GABA(A) receptor modulating constituents from the
      rhizomes of Actaea racemosa.
AB  - Black cohosh (Actaea racemosa) is a frequently used herbal remedy for the
      treatment of mild climacteric symptoms. In the present study, the modulation of
      gamma-aminobutryic acid (GABA)-induced chloride currents (I(GABA)) through GABA
      type A (GABA(A)) receptors by black cohosh extracts and isolated compounds was
      investigated. GABA(A) receptors, consisting of alpha(1), beta(2), and gamma(2S)
      subunits, were expressed in Xenopus laevis oocytes, and potentiation of I(GABA)
      was measured using the two-microelectrode voltage clamp technique. In a
      bioactivity-guided isolation procedure the positive modulation of I(GABA) could
      be restricted to the plant terpenoid fractions, resulting in the isolation of 11
      cycloartane glycosides, of which four significantly (p < 0.05) enhanced I(GABA).
      The most efficient effect was observed for 23-O-acetylshengmanol 3-O-beta-d
      xylopyranoside (4, 100 MUM), enhancing I(GABA) by 1692 +/- 201%, while actein
      (1), cimigenol 3-O-beta-d-xylopyranoside (6), and 25-O-acetylcimigenol 3-O-alpha
      l-arabinopyranoside (8) were significantly less active. In the absence of GABA,
      only 4 induced small (not exceeding 1% of I(GABA-max)) chloride inward currents
      through GABA(A) receptors. It is hypothesized that the established positive
      allosteric modulation of GABA(A) receptors may contribute to beneficial effects
      of black cohosh extracts in the treatment of climacteric symptoms.

PMID- 21082804
TI  - Mastering a double emulsion in a simple co-flow microfluidic to generate complex
      polymersomes.
AB  - We show that the production and the geometrical shape of complex polymersomes can
      be predicted by varying the flow rates of a simple microdevice using an empirical
      law which predicts the droplet size. This device is constituted of fused silica
      capillaries associated with adjusted tubing sleeves and T-junctions. Studying the
      effect of several experimental parameters, double emulsions containing a
      controlled number of droplets were fabricated. First, this study examines the
      stability of a jet in a simple confined microfluidic system, probing the
      conditions required for droplets production. Then, multicompartmental
      polymersomes were formed, controlling flow velocities. In this work,
      poly(dimethylsiloxane)-graft-poly(ethylene oxide) (PDMS-g-PEO) and
      poly(butadiene)-block-poly(ethyleneoxide) (PBut-b-PEO) amphiphilic copolymers
      were used and dissolved in chloroform/cyclohexane mixture. The ratio of these two
      solvents was adjusted in order to stabilize the double emulsion formation. The
      aqueous suspension contained poly(vinyl alcohol) (PVA), limiting the coalescence
      of the droplets. This work constitutes major progress in the control of double
      emulsion formation in microfluidic devices and shows that complex structures can
      be obtained using such a process.

PMID- 21082805
TI  - Morphology of nanoclusters and nanopillars formed in nonequilibrium surface
      growth for catalysis applications.
AB  - We consider growth of nanoclusters and nanopillars in a model of surface
      deposition and restructuring yielding morphologies of interest in designing
      catalysis applications. Kinetic Monte Carlo numerical modeling yields examples of
      the emergence of face centered cubic (fcc) symmetry surface features in Pt-type
      metal nanostructures, allowing evaluation of the fraction of the resulting active
      sites with desirable properties, such as (111)-like coordination, as well as
      suggesting the optimal growth regimes.

PMID- 21082806
TI  - Structural revision and synthesis of altechromone A.
AB  - The chromone "altechromone A" was synthesized as a substructure in the course of
      natural product synthesis. Its architecture was verified by X-ray analysis, but
      spectroscopic data showed a strong deviation from the reported data. By
      comparison with the synthesized isomers the structure of altechromone A was
      revised.

PMID- 21082808
TI  - Stereomutation of pentavalent compounds: validating the Berry pseudorotation,
      redressing Ugi's turnstile rotation, and revealing the two- and three-arm
      turnstiles.
AB  - A general reaction mechanism describes the qualitative change in chemical
      topology along the reaction pathway. On the basis of this principle, we present a
      method to characterize intramolecular substituent permutation in pentavalent
      compounds. A full description of the geometry around five-coordinate atoms using
      internal coordinates enables the analysis of the structural changes along the
      stereomutational intrinsic reaction coordinate. The fluxional behavior of
      experimentally known pentavalent phosphoranes, silicates, and transition-metal
      complexes has been investigated by density functional theory calculations, and
      three principal mechanisms have been identified: Berry pseudorotation, threefold
      cyclic permutation, and half-twist axial-equatorial interchange. The frequently
      cited turnstile rotation is shown to be equivalent to the Berry pseudorotation.
      In combination with graph theory, this approach provides a means to
      systematically investigate the stereomutation of pentavalent molecules and
      potentially identify hitherto-unknown mechanisms.

PMID- 21082807
TI  - DNA cleavage system of nanosized graphene oxide sheets and copper ions.
AB  - The exploration of efficient DNA intercalative agents (intercalators) is
      essential for understanding DNA scission, repair, and signal transduction. In
      this work, we explored systematically the graphene oxide (GO) interaction with
      DNA molecules using fluorescence spectroscopic (FL) and circular dichroism (CD)
      studies, gel electrophoresis, and DNA thermal denaturation. We demonstrated that
      the GO nanosheets could intercalate efficiently into DNA molecules.
      Significantly, we illustrated that the scission of DNA by GO sheets combining
      with copper ions could take place pronouncedly. The scission of DNA by the
      GO/Cu(2+) system is critically dependent on the concentrations of GO and Cu(2+)
      and their ratio. DNA cleavage ability exhibited by the GO with several other
      metal ions and the fact that GO/Cu(2+)-cleaved DNA fragments can be partially
      relegated suggest that the mechanism of DNA cleavage by the GO/metal ion system
      is oxidative and hydrolytic. The result reveals that the GO/Cu(2+) could be used
      as a DNA cleaving system that should find many practical applications in
      biotechnology and as therapeutic agents.

PMID- 21082809
TI  - Hydrothermal synthesis and characterization of 2D M(II)-Quinate (M = Co,Zn) metal
      organic lattice assemblies: solid-state solution structure correlation in M(II)
      hydroxycarboxylate systems.
AB  - Co(II) and Zn(II) ions exhibit variable reactivity toward O-containing ligands in
      aqueous media, affording isolable materials with distinct solid-state lattice
      properties. d-(-)-quinic acid is a cellular alpha-hydroxycarboxylate metal ion
      binder, which reacts with Co(II) and Zn(II) under pH-specific hydrothermal
      conditions, leading to the isolation of two new species
      [Co(2)(C(7)H(11)O(6))(4)](n).nH(2)O (1) and [Zn(3)(C(7)H(11)O(6))(6)](n).nH(2)O
      (2). Compound 1 was characterized by elemental analysis, spectroscopic techniques
      (FT-IR, UV-visible, EPR), magnetic studies, and X-ray crystallography. Compound 2
      was characterized by elemental analysis, spectroscopic techniques (FT-IR, ESI
      MS), and X-ray crystallography. The 2D molecular lattices in 1 and 2 reveal the
      presence of octahedral M(II) units bound exclusively to quinate in a distinct
      fashion, thereby projecting a unique chemical reactivity in each investigated
      system. The magnetic susceptibility and solid-state/frozen solution EPR data on 1
      support the presence of a high-spin octahedral Co(II) in an oxygen environment,
      having a ground state with an effective spin of S = 1/2. Concurrent aqueous
      speciation studies on the binary Zn(II)-quinate system unravel the nature and
      properties of species arising from Zn(II)-quinate interactions as a function of
      pH and molar ratio. The physicochemical profiles of 1 and 2, in the solid state
      and in solution, earmark the importance of (a) select synthetic hydrothermal
      reactivity conditions, affording new well-defined lattice dimensionality and
      nuclearity M(II)-quinate materials, (b) structural speciation approaches
      delineating solid state-aqueous solution correlations in the binary M(II)-quinate
      systems, and (c) pH-specific chemical reactivity in binary M(II)-quinate systems
      reflecting structurally unique associations of simple aqueous complexes into
      distinctly assembled 2D crystalline lattices.

PMID- 21082810
TI  - A dual-emission Forster resonance energy transfer nanoprobe for sensing/imaging
      pH changes in the biological environment.
AB  - A dual-emission nanoprobe that can sense changes in the environmental pH is
      designed based on the concept of pH-responsive Forster resonance energy transfer
      induced by the conformational transition of an associating polyelectrolyte, N
      palmitoyl chitosan, bearing a donor (Cy3) or an acceptor (Cy5) moiety. We
      demonstrate that the developed pH-responsive nanoprobe can be used to
      ratiometrically image and thus discriminate the pH changes in the biological
      environment at different length scales.

PMID- 21082811
TI  - Chiral ruthenium Lewis acid catalyzed intramolecular Diels-Alder reactions.
AB  - Single point binding ruthenium Lewis acid catalysts [Ru(acetone)(S,S)-BIPHOP
      F)Cp][SbF(6)] ((S,S)-1b) and [Ru(acetone)(S,S)-BIPHOP-F)(indenyl)][SbF(6)] ((S,S)
      1c) efficiently catalyze intramolecular Diels-Alder (IMDA) reactions under mild
      conditions to afford the endo cycloaddition products as the major product in
      excellent yields with high diastereo- and enantioselectivities.

PMID- 21082812
TI  - Regioselectivity in intermolecular Pauson-Khand reactions of dissymmetric
      fluorinated alkynes.
AB  - Stoichiometric and catalytic intermolecular Pauson-Khand reactions (PKRs) of
      dissymmetric fluorinated alkynes were performed, affording regioselectively alpha
      fluorinated cyclopentenones. Ethyl 4,4,4-trifluorobutynoate was an excellent
      substrate; its reaction with norbornadiene gave the corresponding PKR adduct in
      good yield and complete regioselectivity. Conjugate addition of nitroalkanes or
      cyanide to this adduct is stereospecific and entails concomitant loss of a
      trifluoromethyl group. This reaction can be exploited to prepare cyclopentenones
      featuring quaternary centers.

PMID- 21082813
TI  - Approach toward the total synthesis of 5-hydroxyaloin A.
AB  - The synthesis of a thiomethyl analogue of 5-hydroxyaloin A has been achieved
      using benzyne and naphthyne [4 + 2] cycloadditions with substituted furans. A
      regiocontrolled cycloaddition was achieved using a silicon tether, and a
      regioselective ring opening was accomplished using a sulfide as a directing
      group.

PMID- 21082814
TI  - Effects of cell culture media on the dynamic formation of protein-nanoparticle
      complexes and influence on the cellular response.
AB  - The development of appropriate in vitro protocols to assess the potential
      toxicity of the ever expanding range of nanoparticles represents a challenging
      issue, because of the rapid changes of their intrinsic physicochemical properties
      (size, shape, reactivity, surface area, etc.) upon dispersion in biological
      fluids. Dynamic formation of protein coating around nanoparticles is a key
      molecular event, which may strongly impact the biological response in
      nanotoxicological tests. In this work, by using citrate-capped gold nanoparticles
      (AuNPs) of different sizes as a model, we show, by several spectroscopic
      techniques (dynamic light scattering, UV-visible, plasmon resonance light
      scattering), that proteins-NP interactions are differently mediated by two widely
      used cellular media (i.e., Dulbecco Modified Eagle's medium (DMEM) and Roswell
      Park Memorial Institute medium (RPMI), supplemented with fetal bovine serum). We
      found that, while DMEM elicits the formation of a large time-dependent protein
      corona, RPMI shows different dynamics with reduced protein coating.
      Characterization of these nanobioentities was also performed by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and mass spectroscopy, revealing that
      the average composition of protein corona does not reflect the relative abundance
      of serum proteins. To evaluate the biological impact of such hybrid
      bionanostructures, several comparative viability assays onto two cell lines (HeLa
      and U937) were carried out in the two media, in the presence of 15 nm AuNPs. We
      observed that proteins/NP complexes formed in RPMI are more abundantly
      internalized in cells as compared to DMEM, overall exerting higher cytotoxic
      effects. These results show that, beyond an in-depth NPs characterization before
      cellular experiments, a detailed understanding of the effects elicited by cell
      culture media on NPs is crucial for standardized nanotoxicology tests.

PMID- 21082815
TI  - A molecular template designed by the modification of a helix-forming beta-1,3
      glucan polysaccharide to fabricate one-dimensional nanostructures.
AB  - We report the development of a new templating molecule designed by the
      modification of a helix-forming beta-1,3-glucan polysaccharide to the cationic
      semiartificial one and its application to the fabrication of one-dimensional (1D)
      gold nanostructures by simple photoirradiation. Transmission electron microscopy
      observation showed that Au(III) ions are primarily reduced to gold nanoparticles
      self-assembling into the 1D array with the aid of the cationic beta-1,3-glucan
      polysaccharide, which gradually fuse into the 1D gold nanostructure with the
      tapelike structure. The gold nanotape structure could not be created by neutral
      beta-1,3-glucan polysaccharides or random coil synthetic cationic polymers. These
      findings consistently support the view that Au(III) ions are reduced by
      unmodified OH groups to gold nanoparticles under the photoirradiation, which are
      wrapped in the helical structure of the cationic beta-1,3-glucan polysaccharide
      and eventually fuse into gold nanotapes. One may regard, therefore, that this
      cationic beta-1,3-glucan polysaccharide can act as an "all-in-one" template
      playing three roles of reduction, 1D arrangement, and fusion of gold
      nanoparticles. In addition, we found an interesting phenomenon that the obtained
      gold nanotapes coated with cationic beta-1,3-glucan polysaccharides show unique
      surface-enhanced Raman scattering for anionic porphyrines organized on the
      surface of gold nanotapes through the electrostatic interaction.

PMID- 21082817
TI  - Molecular bridging of silicon nanogaps.
AB  - The highly doped electrodes of a vertical silicon nanogap device have been
      bridged by a 5.85 nm long molecular wire, which was synthesized in situ by
      grafting 4-ethynylbenzaldehyde via C-Si links to the top and bottom electrodes
      and thereafter by coupling an amino-terminated fluorene unit to the aldehyde
      groups of the activated electrode surfaces. The number of bridging molecules is
      constrained by relying on surface roughness to match the 5.85 nm length with an
      electrode gap that is nominally 1 nm wider and may be controlled by varying the
      reaction time: the device current increases from <=1 pA at 1 V following the
      initial grafting step to 10-100 nA at 1 V when reacted for 5-15 min with the
      amino-terminated linker and 10 MUA when reacted for 16-53 h. It is the first time
      that both ends of a molecular wire have been directly grafted to silicon
      electrodes, and these molecule-induced changes are reversible. The bridges detach
      when the device is rinsed with dilute acid solution, which breaks the imine links
      of the in situ formed wire and causes the current to revert to the subpicoampere
      leakage value of the 4-ethynylbenzaldehyde-grafted nanogap structure.

PMID- 21082816
TI  - Transfer of biosynthesized gold nanoparticles from water into an ionic liquid
      using alkyltrimethyl ammonium bromide: an anion-exchange process.
AB  - Biosynthesized gold nanoparticles (GNPs) were transferred from water to a
      hydrophobic ionic liquid (IL), [Bmim]PF(6), with the assistance of alkyl
      trimethyl ammonium bromide. The phase transfer mechanism was illustrated through
      the exemplification of cetyltrimethyl ammonium bromide (CTAB). Interaction
      between GNPs and CTAB was demonstrated through zeta potential analysis. Moreover,
      an anion-exchange process was discovered between CTAB and IL. During the process,
      the hydrophobic CTAPF(6) formed in situ on the GNPs led to the hydrophobization
      and thus phase transfer of the GNPs. The phase transfer efficiency was found to
      be size-dependent.

PMID- 21082818
TI  - Highly conductive multifunctional graphene polycarbonate nanocomposites.
AB  - Graphene nanosheet-bisphenol A polycarbonate nanocomposites (0.027-2.2 vol %)
      prepared by both emulsion mixing and solution blending methods, followed by
      compression molding at 287  degrees C, exhibited dc electrical percolation
      threshold of ~0.14 and ~0.38 vol %, respectively. The conductivities of 2.2 vol %
      graphene nanocomposites were 0.512 and 0.226 S/cm for emulsion and solution
      mixing. The 1.1 and 2.2 vol % graphene nanocomposites exhibited frequency
      independent behavior. Inherent conductivity, extremely high aspect ratio, and
      nanostructure directed assembly of the graphene using PC nanospheres are the main
      factors for excellent electrical properties of the nanocomposites. Dynamic
      tensile moduli of nanocomposites increased with increasing graphene in the
      nanocomposite. The glass transition temperatures were decreased with increasing
      graphene for the emulsion series. High-resolution electron microscopy (HR-TEM)
      and small-angle neutron scattering (SANS) showed isolated graphene with no
      connectivity path for insulating nanocomposites and connected nanoparticles for
      the conductive nanocomposites. A stacked disk model was used to obtain the
      average particle radius, average number of graphene layers per stack, and stack
      spacing by simulation of the experimental SANS data. Morphology studies indicated
      the presence of well-dispersed graphene and small graphene stacking with infusion
      of polycarbonate within the stacks.

PMID- 21082819
TI  - Isotopic disequilibrium during uptake of atmospheric CO2 into mine process
      waters: implications for CO2 sequestration.
AB  - Dypingite, a hydrated Mg-carbonate mineral, was precipitated from high-pH, high
      salinity solutions to investigate controls on carbon fixation and to identify the
      isotopic characteristics of mineral sequestration in mine tailings. delta(13)C
      values of dissolved inorganic carbon content and synthetic dypingite are
      significantly more negative than those predicted for equilibrium exchange of
      CO(2) gas between the atmosphere and solution. The measured delta(13)C of aqueous
      carbonate species is consistent with a kinetic fractionation that results from a
      slow diffusion of atmospheric CO(2) into solution. During dypingite
      precipitation, dissolved inorganic carbon concentrations decrease and delta(13)C
      values become more negative, indicating that the rate of CO(2) uptake into
      solution was outpaced by the rate of carbon fixation within the precipitate. This
      implies that CO(2) gas uptake is rate-limiting to CO(2) fixation. delta(13)C of
      carbonate mineral precipitates in mine tailings and of DIC in mine process waters
      display similar (13)C-depletions that are inconsistent with equilibrium
      fractionation. Thus, the rate of carbon fixation in mine tailings may also be
      limited by supply of CO(2). Carbon sequestration could be accelerated by
      increasing the partial pressure of CO(2) in tailings ponds or by using chemicals
      that enhance the uptake of gaseous CO(2) into aqueous solution.

PMID- 21082820
TI  - Electrodeposited nanoporous versus nanoparticulate ZnO films of similar roughness
      for dye-sensitized solar cell applications.
AB  - We present a comparative study of two different ZnO porous film morphologies for
      dye-sensitized solar cell (DSSC) fabrications. Nanoparticulate ZnO was prepared
      by the doctor-blade technique starting from a paste containing ZnO nanoparticles.
      Nanoporous ZnO films were grown by a soft template-assisted electrochemical
      growth technique. The film thicknesses were adjusted at similar roughness of
      about 300 in order to permit a worthy comparison. The effects on the cell
      performances of sensitization by dyes belonging to three different families,
      namely, xanthene (eosin Y) and indoline (D102, D131, D149 and D205) organic dyes
      as well as a ruthenium polypyridine complex (N719), have been investigated. The
      mesoporous electrodeposited matrix exhibits significant morphological changes
      upon the photoanode preparation, especially upon the dye sensitization, that
      yield to a dramatic change of the inner layer morphology and increase in the
      layer internal specific surface area. In the case of indoline dyes, better
      efficiencies were found with the electrodeposited ZnO porous matrixes compared to
      the nanoparticulate ones, in spite of significantly shorter electron lifetimes
      measured by impedance spectroscopy. The observation is interpreted in terms of
      much shorter transfer time in the oxide in the case of the electrodeposited ZnO
      films. Among the tested dyes, the D149 and D205 indoline organic dyes with a
      strong acceptor group were found the most efficient with the best cell over 4.6%
      of overall conversion efficiency.

PMID- 21082821
TI  - Negative differential resistance in C60-based electronic devices.
AB  - Unlike single-C(60)-based devices, molecular assemblies based on two or more
      appropriately connected C(60) molecules have the potential to exhibit negative
      differential resistance (NDR). In this work, we evaluate electron transport
      properties of molecular devices built from two C(60) molecules connected by an
      alkane chain, using a nonequilibrium Green function technique implemented within
      the framework of density functional theory. We find that electronic conduction in
      these systems is mediated by the lowest unoccupied molecular orbitals (LUMOs) of
      C(60), as in the case of a single-C(60)-based device. However, as the positions
      of the LUMOs are pinned to the chemical potentials of their respective
      electrodes, their relative alignment shifts with applied bias and leads to a NDR
      at a very low bias. Furthermore, the position and magnitude of the NDR can be
      tuned by chemical modification of the C(60) molecules. The role of the attached
      molecules is to shift the LUMO position and break the symmetry between the
      forward and reverse currents. The NDR feature can also be controlled by changing
      the length of the alkane linker. The flexibility and richness of C(60)-based
      molecular electronics components point to a potentially promising route for the
      design of molecular devices and chemical sensors.

PMID- 21082823
TI  - Monitoring and modeling endosulfan in Chinese surface soil.
AB  - Endosulfan is a currently used organochlorine pesticide in China, with annual
      usage of 2300 t between 1994 and 2004. Concentrations of endosulfan (including
      alpha- and beta-isomers and their metabolite endosulfan sulfate) were reported
      for surface soil collected in 2005 at 141 sites (6 background, 95 rural, and 40
      urban) across China. The concentrations of total endosulfan (sum of alpha
      endosulfan, beta-endosulfan, and endosulfan sulfate) at all sites ranged from BDL
      (below detection limit) to 19000 pg/g dry weight (dw), with geometric mean (GM)
      120 pg/g dw. Rural soils had the highest total endosulfan concentrations, with GM
      160 pg/g dw, followed by urban soils (GM = 83 pg/g dw) and background soils (GM =
      38 pg/g dw). The observed soil concentrations of alpha-endosulfan (GM = 6.5 pg/g
      dw) were much lower than those of beta-endosulfan (GM = 49 pg/g dw) and
      endosulfan sulfate (GM = 47 pg/g dw). The fractional abundance of alpha
      endosulfan F(alpha-endo) [alpha-endosulfan/(alpha-endosulfan + beta-endosulfan)]
      for all soils ranged from 0.00040 to 0.91, with GM 0.10, much lower than those in
      technical products (ranged from 0.67 to 0.7), which most likely reflects that
      alpha-endosulfan is more volatile and degrades faster than beta-endosulfan in
      soil. Consequently, half-life of beta-endosulfan in soil is expected longer than
      alpha-endosulfan. Significant correlation between endosulfan sulfate and its
      parent isomers suggested that the presence of endosulfan sulfate originated from
      its parent isomers. Based on multiple linear regression model, inventories of
      endosulfan sulfate in Chinese agricultural soil in 2004 with a 1/4 degrees 
      longitude * 1/6 degrees  latitude resolution are established. Comparison between
      field measurements and modeling results showed significant correlations between
      the modeled and measured endosulfan concentrations, and 89%, 83%, and 70% of
      monitoring data fell between the lowest and the highest modeled concentrations
      for alpha- and beta-endosulfan and endosulfan sulfate, respectively. The good
      agreement lends credibility to modeled soil concentrations of endosulfan. To our
      knowledge, this is the first soil concentration inventory for endosulfan sulfate,
      which paves the way for further study on its environmental behavior.

PMID- 21082822
TI  - Quantum dot DNA bioconjugates: attachment chemistry strongly influences the
      resulting composite architecture.
AB  - The unique properties provided by hybrid semiconductor quantum dot (QD)
      bioconjugates continue to stimulate interest for many applications ranging from
      biosensing to energy harvesting. Understanding both the structure and function of
      these composite materials is an important component in their development. Here,
      we compare the architecture that results from using two common self-assembly
      chemistries to attach DNA to QDs. DNA modified to display either a terminal
      biotin or an oligohistidine peptidyl sequence was assembled to
      streptavidin/amphiphilic polymer- or PEG-functionalized QDs, respectively. A
      series of complementary acceptor dye-labeled DNA were hybridized to different
      positions on the DNA in each QD configuration and the separation distances
      between the QD donor and each dye-acceptor probed with Forster resonance energy
      transfer (FRET). The polyhistidine self-assembly yielded QD-DNA bioconjugates
      where predicted and experimental separation distances matched reasonably well.
      Although displaying efficient FRET, data from QD-DNA bioconjugates assembled
      using biotin-streptavidin chemistry did not match any predicted separation
      distances. Modeling based upon known QD and DNA structures along with the linkage
      chemistry and FRET-derived distances was used to simulate each QD-DNA structure
      and provide insight into the underlying architecture. Although displaying some
      rotational freedom, the DNA modified with the polyhistidine assembles to the QD
      with its structure extended out from the QD-PEG surface as predicted. In
      contrast, the random orientation of streptavidin on the QD surface resulted in
      DNA with a wide variety of possible orientations relative to the QD which cannot
      be controlled during assembly. These results suggest that if a particular QD
      biocomposite structure is desired, for example, random versus oriented, the type
      of bioconjugation chemistry utilized will be a key influencing factor.

PMID- 21082824
TI  - Interplay of electrical forces for alignment of sub-100 nm electrospun nanofibers
      on insulator gap collectors.
AB  - We present a quantitative design methodology for optimizing insulator gap width,
      gap resistivity, and collector to needle height for the alignment of sub-100 nm
      electrospun nanofibers at insulator gaps of metal collectors. Enhancement of the
      spatial extent of alignment forces at insulator gaps, due to the concerted action
      of attractive stretching forces from the modified electric fields and repulsive
      forces from residual charges on undischarged fibers in the gap, is studied. At
      gap widths considerably smaller than the collector to needle height (<2%), the
      spatial extent of stretching forces is large as evidenced by successive reduction
      in nanofiber size with gap width; however, the low magnitude of repulsive forces
      limits the degree of nanofiber alignment. At successively larger gap widths less
      than the needle height, the spatial extent of the stretching forces is gradually
      restricted toward the metal-insulator edges, while the influence of repulsive
      forces is gradually extended across the rest of the spatial extent of the gap, to
      cause enhanced nanofiber alignment through the concerted action of these forces.
      At gap widths greater than the needle height, the limited spatial extent and
      lowered maximum value of the stretching forces at the metal-insulator edge
      reduces their influence on fiber stretching and alignment. The collection of sub
      100 nm electrospun poly(lactic acid-co-glycolic acid) nanofibers with a good
      degree of alignment (<=10 degrees  deviation) is found to require intermediate
      size gaps (~2% of needle height) of high resistivity (>=10(12) ohm-cm), to
      enhance the spatial extent of stretching forces while maintaining the dominance
      of repulsive forces due to residual charge across a majority of the spatial
      extent of the gap.

PMID- 21082825
TI  - Morphology and breaking of latex particle deposits at a cylindrical collector in
      a microfluidic chamber.
AB  - We report an analysis for the morphology and breaking behavior of deposits of
      spherical latex particles (1 and 3.6 MUm in diameter) at a cylindrical collector
      in a microfluidic channel fabricated by soft-lithography. In-situ observation of
      particle deposition over a large range of flow rate conditions evidence the
      relationship between deposit morphology and mode of particle transport toward the
      collector. For low Peclet number (Pe), particle deposits are nearly uniform all
      over the collector surface except at the rear where particles do not attach. Upon
      increase of Pe, deposits gradually adopt a columnar morphology at the collector
      stagnation point. These results are qualitatively consistent with previously
      reported Monte Carlo simulations of deposits formation in stagnation point flow
      systems. However, these simulations fail to quantitatively predict the observed
      deposition at the rear of the collector for sufficiently high flow rate.
      Additional deposit breaking experiments together with numerical evaluations of
      particle flux around the collector suggest that such "anomalous" deposition at
      large Pe is significantly governed by concomitant detachment of deposited
      particles at the stagnation point and the presence of recirculation flow at the
      collector rear. Finally, kinetics of deposition are discussed in connection with
      particle size-dependence of deposit breaking features.

PMID- 21082826
TI  - Photochromism and photopolymerization induced mesophase transitions in mixtures
      of spiropyran and mesogenic diacrylate.
AB  - A phase diagram of a binary mixture of photochromic molecule (spiropyran) and
      mesogenic diacrylate monomer has been established by means of differential
      scanning calorimetry and polarized optical microscopy. Subsequently, a
      theoretical phase diagram has been calculated by self-consistently solving the
      combined Flory-Huggins free energy for isotropic mixing, Maier-Saupe free energy
      for nematic ordering, and phase field free energy for crystal solidification. The
      phase diagram thus obtained consists of various coexistence regions involving
      single-phase crystals, pure nematic, crystal + liquid, crystal + nematic, and
      crystal + crystal coexistence gaps. Under UV irradiation, both SP and SP/RM257
      mixtures showed the lowering trend of the melting points, which may be attributed
      to the plasticization effect by the merocyanine isomers. When UV light is
      illuminated on the 2/98 SP/RM257 mixture for an extended period, mesogenic
      diacrylate in the mixtures gets polymerized, showing the permanent fixation of
      isotropic and nematic structures due to the network formation of RM257 caused by
      the biradicals in the merocyanine intermediate.

PMID- 21082827
TI  - Density distribution in the liquid Hg-sapphire interface.
AB  - We present the results of a computer simulation study of the liquid density
      distribution normal to the interface between liquid Hg and the reconstructed
      (0001) face of sapphire. The simulations are based on an extension of the self
      consistent quantum Monte Carlo scheme previously used to study the structure of
      the liquid metal-vapor interface. The calculated density distribution is in very
      good agreement with that inferred from the recent experimental data of Tamam et
      al. (J. Phys. Chem. Lett. 2010, 1, 1041-1045). We conclude that, to account for
      the difference in structure between the liquid Hg-vapor and liquid-Hg
      reconstructed (0001) Al(2)O(3) interfaces, it is not necessary to assume there is
      charge transfer from the Hg to the Al(2)O(3). Rather, the available experimental
      data are adequately reproduced when the van der Waals interactions of the Al and
      O atoms with Hg atoms and the exclusion of electron density from Al(2)O(3) via
      repulsion of the electrons from the closed shells of the ions in the solid are
      accounted for.

PMID- 21082828
TI  - Fractionating nanosilver: importance for determining toxicity to aquatic test
      organisms.
AB  - This investigation applied novel techniques for characterizing and fractionating
      nanosilver particles and aggregates and relating these measurements to
      toxicological endpoints. The acute toxicity of eight nanosilver suspensions of
      varying primary particle sizes (10-80 nm) and coatings (citrate,
      polyvinylpyrrolidone, EDTA, proprietary) was assessed using three aquatic test
      organisms (Daphnia magna, Pimephales promelas, Pseudokirchneriella subcapitata).
      When 48-h lethal median concentrations (LC50) were expressed as total silver,
      both D. magna and P. promelas were significantly more sensitive to ionic silver
      (Ag(+)) as AgNO(3) (mean LC50 = 1.2 and 6.3 MUg/L, respectively) relative to a
      wide range in LC50 values determined for the nanosilver suspensions (2 -126
      MUg/L). However, when LC50 values for nanosilver suspensions were expressed as
      fractionated nanosilver (Ag(+) and/or <4 nm particles), determined by
      ultracentrifugation of particles and confirmed field-flow-fractograms, the LC50
      values (0.3-5.6 MUg/L) were comparable to the values obtained for ionic Ag(+) as
      AgNO(3). These results suggest that dissolved Ag(+) plays a critical role in
      acute toxicity and underscores the importance of characterizing dissolved
      fractions in nanometal suspensions.

PMID- 21082829
TI  - Role of the charge-transfer state in the electronic absorption of protonated
      hydrocarbon molecules.
AB  - The vibrationally resolved electronic spectra of isolated protonated polycyclic
      aromatic hydrocarbons (PAHs)--naphthalene, anthracene, and tetracene--have been
      recorded via neutral photofragment spectroscopy. The S1<-S0 transitions are all
      in the visible region and do not show a monotonic red shift as a function of the
      molecular size, as observed for the neutral analogues. Comparison with ab initio
      calculations indicates that this behavior is due to the nature of the excited
      state, which has a pronounced charge-transfer character for protonated linear
      PAHs with an even number of aromatic rings.

PMID- 21082831
TI  - Reactive nitrogen species in acetaminophen-induced mitochondrial damage and
      toxicity in mouse hepatocytes: a cautionary note on the impact of cell culture
      conditions.

PMID- 21082832
TI  - Efficient carboazidation of alkenes using a radical desulfonylative azide
      transfer process.
AB  - The radical-mediated carboazidation of terminal alkenes using electrophilic
      alkanesulfonyl azides is reported. A single reagent delivers the necessary
      electrophilic alkyl radical as well as the azido group, and good yields are
      obtained by using a moderate excess of the carboazidating reagent (1.5-2 equiv).
      Interestingly, in addition to the starting sulfonyl azide, this method requires
      only the use of a radical initiator, di-tert-butyldiazene. In terms of atom
      economy, this azide transfer reaction is close to ideal, as SO2 (1 equiv) is the
      only side product. The synthetic potential of this process has been demonstrated
      by a formal synthesis of the alkaloid lepadiformine C.

PMID- 21082834
TI  - Microfluidic melt emulsification for encapsulation and release of actives.
AB  - A microfluidic melt emulsification method for encapsulation and release of
      actives is presented. Using a water-in-oil-in-water (W-O-W) double emulsion
      template, solid capsules can be formed by freezing the middle shell phase.
      Actives encapsulated inside the solid shell can be controllably and rapidly
      released by applying a temperature trigger to melt the shell. The choice of the
      shell materials can be chosen to accommodate the storage and release temperatures
      specific to the applications. In addition, we have also demonstrated the same
      concept to encapsulate multiple actives in multicompartment capsules, which are
      promising as multifunctional capsules and microreactors.

PMID- 21082835
TI  - Energy landscapes associated with macromolecular conformational changes from
      endpoint structures.
AB  - Conformational changes modulate macromolecular function by promoting the specific
      binding of ligands (such as in antigen recognition) or the stabilization of
      transition states in enzymatic reactions. However, quantitative characterization
      of the energetics underlying dynamic structural interconversions is still
      challenging and lacks a unified method. Here, we introduce a novel in silico
      approach based on the combined use of essential dynamics sampling and
      nonequilibrium free-energy calculations to obtain quantitative data on
      conformational energy landscapes. This technique allows the unbiased
      investigation of highly complex rearrangements, and does not require the crucial
      definition of user-defined collective variables. We show that free-energy values
      derived from profiles connecting the unliganded and ligand-bound X-ray structures
      of a bacterial nucleoside hydrolase match the experimental binding constant. This
      approach also provides first evidence for a rate-limiting character of the
      conformational transition in this enzyme, and an unexpected role of the
      protonation state of a single residue in regulating substrate binding and product
      release.

PMID- 21082836
TI  - Meta nitration of thiacalixarenes.
AB  - Nitration of thiacalix[4]arene, immobilized in the 1,3-alternate conformation,
      leads regioselectively to meta-substituted products. Depending on the reaction
      conditions, mono- and dinitro-derivatives can be isolated in acceptable yields.
      This unique substitution pattern is inaccessible in classical calixarene
      chemistry, and yields inherently chiral compounds, which makes thiacalixarenes
      very attractive as building blocks or molecular scaffolds.

PMID- 21082837
TI  - Functional mesoporous metal-organic frameworks for the capture of heavy metal
      ions and size-selective catalysis.
AB  - By using Zn(4)O(CO(2))(6) as secondary building units (SBUs) and two extended
      ligands containing amino functional groups, TATAB and BTATB (TATAB = 4,4',4''-s
      triazine-1,3,5-triyltri-p-aminobenzoate and BTATB = 4,4',4''-(benzene-1,3,5
      triyltris(azanediyl))tribenzoate), two isostructural mesoporous metal-organic
      frameworks (MOFs) with cavities up to 2.73 nm, designated as PCN-100 and PCN-101
      (PCN represents porous coordination network), have been synthesized. N(2)
      sorption isotherms of both PCN-100 and -101 showed typical type IV behavior,
      indicating their mesoporous nature. The TATAB ligand that comprises PCN-100 was
      employed to capture heavy metal ions (Cd(II) and Hg(II)) by constructing
      complexes within the pores with a possible coordination mode similar to that
      found in aminopyridinato complexes. This reveals that mesoporous materials such
      as PCN-100 can be applied in the elimination of heavy metal ions from waste
      liquid. In addition, both PCNs-100 and -101 exhibit size-selective catalytic
      activity toward the Knoevenagel condensation reaction.

PMID- 21082838
TI  - Pd(II)-catalyzed carbonylation of C(sp3)-H bonds: a new entry to 1,4-dicarbonyl
      compounds.
AB  - Pd(II)-catalyzed beta-C(sp(3))-H carbonylation of N-arylamides under CO (1 atm)
      has been achieved. Following amide-directed C(sp(3))-H cleavage and insertion of
      CO into the resulting [Pd(II)-C(sp(3))] bond, intramolecular C-N reductive
      elimination gave the corresponding succinimides, which could be readily converted
      to 1,4-dicarbonyl compounds. This method was found to be effective with
      substrates containing alpha-hydrogen atoms and could be applied to effect
      methylene C(sp(3))-H carbonylation of cyclopropanes.

PMID- 21082839
TI  - Selective (15)N-labeling and analysis of (13)C-(15)N J couplings as an effective
      tool for studying the structure and azide-tetrazole equilibrium in a series of
      tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines.
AB  - Two general methods for the selective incorporation of an (15)N-label in the
      azole ring of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines
      were developed. The first approach included treatment of azinylhydrazides with
      (15)N-labeled nitrous acid, and the second approach was based on fusion of the
      azine ring to [2-(15)N]-5-aminotetrazole. The synthesized compounds were studied
      by (1)H, (13)C, and (15)N NMR spectroscopy in both DMSO and TFA solution, in
      which the azide-tetrazole equilibrium is shifted to tetrazole and azide forms,
      respectively. Incorporation of the (15)N-label led to the appearance of (13)C
      (15)N J coupling constants (J(CN)), which can be measured easily using either 1D
      (13)C spectra with selective (15)N decoupling or with amplitude modulated 1D
      (13)C spin-echo experiments with selective inversion of the (15)N nuclei. The
      observed J(CN) patterns permit unambiguous determination of the type of fusion
      between the azole and azine rings in tetrazolo[1,5-b][1,2,4]triazine derivatives.
      Joint analysis of J(CN) patterns and (15)N chemical shifts was found to be the
      most efficient way to study the azido-tetrazole equilibrium.

PMID- 21082840
TI  - Advanced electron paramagnetic resonance and density functional theory study of a
      {2Fe3S} cluster mimicking the active site of [FeFe] hydrogenase.
AB  - Despite extensive investigations of the active site of the [FeFe] hydrogenases,
      many details concerning the properties of the "hydrogen converting cluster" are
      not yet fully understood. The complexity of the so-called H-cluster is one of the
      main difficulties in studying the properties of its components. The present study
      is aimed at the mixed-valence EPR active [Fe2(MU
      CO)(CO)3(CN)2{MeSCH2C(Me)(CH2S)2}](1-) that is structurally closely related to
      the redox active binuclear part of the H-cluster in its CO-inhibited oxidized
      state. In this work, we present a characterization of this compound by advanced
      pulse EPR methods. The accurate determination of the (57)Fe, (1)H, (2)H, (14)N,
      and (15)N electron nuclear hyperfine interactions provided a very detailed
      picture of the electronic structure of this complex. A theoretical study using
      density functional theory (DFT) calculations identified possible isomers of the
      compound and further refined the knowledge about its properties. It was found
      that upon one electron oxidation of the parent Fe(I)-Fe(I) complex, the dominant
      mixed-valence Fe(I)-Fe(II) species is the one in which the CN ligand of the iron
      center that is distal to the thioether moves from the basal to the apical
      position. The unpaired spin distribution of the model complex is found to be
      clearly different from that of the native H-cluster. These differences are
      discussed and provide new insight into the functional features of the [FeFe]
      hydrogenase active site.

PMID- 21082841
TI  - Direct growth of short single-walled carbon nanotubes with narrow-chirality
      distribution by time-programmed plasma chemical vapor deposition.
AB  - We have realized the direct growth of the short-length (<100 nm) single-walled
      carbon nanotubes (SWNTs) with a narrow-chirality distribution by time-programmed
      plasma chemical vapor deposition (TP-PCVD). Transmission electron microscope and
      atomic force microscope analyses reveal that the very short (<100 nm) SWNTs are
      selectively grown by precisely controlling their growth time on the order of a
      few seconds. Direct photoluminescence excitation measurements also show that the
      chirality distribution of the short SWNTs is fairly narrow, and (7, 6) and (8, 4)
      dominant short SWNTs are successfully synthesized by TP-PCVD.

PMID- 21082842
TI  - Synthesis of poly(amino)ester dendrimers via active cyanomethyl ester
      intermediates.
AB  - A novel strategy for the synthesis of poly(amino)ester dendrimers was developed
      on the basis of active cyanomethyl ester intermediates and an iteration of four
      consecutive steps of deprotection, activation, transesterification, and
      scavenging.

PMID- 21082843
TI  - A unified mechanistic view on the Morita-Baylis-Hillman reaction: computational
      and experimental investigations.
AB  - The thermodynamic properties and reaction mechanism of the Morita-Baylis-Hillman
      (MBH) reaction have been investigated through experimental and computational
      techniques. The impossibility to accelerate this synthetically valuable
      transformation by increasing the reaction temperature has been rationalized by
      variable-temperature experiments and MP2 theoretical calculations of the reaction
      thermodynamics. An increase in temperature results in a switching of the
      equilibrium to the reactants occurring at even moderate temperature levels. The
      complex reaction mechanism for the MBH reaction has been investigated through an
      in-depth analysis of the suggested alternative pathways, using the M06-2X
      computational method. The results provided by this theoretical approach are in
      agreement with all the experimental/kinetic evidence such as reaction order,
      acceleration by protic species (methanol, phenol), and autocatalysis. In
      particular, the existing controversy about the character of the key proton
      transfer in the MBH reaction (Aggarwal versus McQuade pathways) has been
      resolved. Depending on the specific reaction conditions both suggested pathways
      are competing mechanisms, and depending on the amount of protic species and the
      reaction progress (early or late stage) either of the two mechanisms will be
      favored.

PMID- 21082844
TI  - Monte Carlo simulation of self-assembly of symmetric ABC three-arm star
      copolymers under cylindrical confinement.
AB  - Self-assembly of symmetric ABC three-arm star copolymers confined in cylindrical
      nanopores is investigated by means of a lattice Monte Carlo simulation method.
      The dependence of morphologies on the degree of confinement and preference of
      pore surface is studied systematically. For the symmetric ABC three-arm star
      copolymers which form polygonal cylinder structures with periodic spacing L(0) in
      bulk, various novel structures are observed inside the nanopores. In the
      nanopores with a neutral surface, we find a minimum diameter value (D(min) ~
      L(0)) under which helical arranged droplets are formed; otherwise, parallel
      polygonal cylinder structures are identified. By adjusting the preference between
      component A and the pore surfaces, a number of novel structures such as A
      cylinder + BC single-strand helix and complex multilayer double helices are
      identified. Additionally, the confinement-induced morphology transition is
      interpreted by the frustration parameter D/L(0).

PMID- 21082845
TI  - Advancing the mechanistic understanding of an enantioselective palladium
      catalyzed alkene difunctionalization reaction.
AB  - The mechanism of an enantioselective palladium-catalyzed alkene
      difunctionalization reaction has been investigated. Kinetic analysis provides
      evidence of turnover-limiting attack of a proposed quinone methide intermediate
      with MeOH and suggests that copper is involved in productive product formation,
      not just catalyst turnover. Through examination of substrate electronic effects,
      a Jaffe relationship was observed correlating rate to electronic perturbation at
      two positions of the substrate. Ligand effects were evaluated to provide evidence
      of rapid ligand exchange between palladium and copper as well as a correlation
      between ligand electronic nature and enantioselectivity.

PMID- 21082846
TI  - Effects of electrolyte concentration on the rotational dynamics of resorufin.
AB  - We report on the rotational diffusion dynamics of the anionic chromophore
      resorufin in water and N-octyl-2-pyrrolidone (NOP) solutions as a function of
      solution electrolyte concentration. Our data show that resorufin exhibits a
      single exponential anisotropy decay in aqueous solutions containing up to 0.1 M
      lithium perchlorate (LiClO(4)). In contrast to the observed behavior of resorufin
      in pure NOP, where biexponential decay occurs, we also observe a single
      exponential anisotropy decay for resorufin in NOP with the addition of up to 0.1
      M tetrabutylammonium bromide (TBAB) or tetraoctylammonium bromide (TOAB). For
      resorufin in NOP, the reorientation time constant increases with increasing
      electrolyte concentration, consistent with complexation between the resorufin
      anion and the electrolyte ammonium cation. We observe a qualitatively different
      trend in the aqueous resorufin solutions and understand these data for both
      solvent systems in the context of interactions between the chromophore and
      cationic species present.

PMID- 21082847
TI  - Ligand bridging-angle-driven assembly of molecular architectures based on
      quadruply bonded Mo-Mo dimers.
AB  - A systematic exploration of the assembly of Mo2(O2C-)4-based metal-organic
      molecular architectures structurally controlled by the bridging angles of rigid
      organic linkers has been performed. Twelve bridging dicarboxylate ligands were
      designed to be of different sizes with bridging angles of 0, 60, 90, and 120
      degrees  while incorporating a variety of nonbridging functional groups, and
      these ligands were used as linkers. These dicarboxylate linkers assemble with
      quadruply bonded Mo-Mo clusters acting as nodes to give 13 molecular
      architectures, termed metal-organic polygons/polyhedra with metal cluster node
      arrangements of a linear shape, triangle, octahedron, and cuboctahedron/anti
      cuboctahedron. The syntheses of these complexes have been optimized and their
      structures determined by single-crystal X-ray diffraction. The results have shown
      that the shape and size of the resulting molecular architecture can be controlled
      by tuning the bridging angle and size of the linker, respectively.
      Functionalization of the linker can adjust the solubility of the ensuing
      molecular assembly but has little or no effect on the geometry of the product.
      Preliminary gas adsorption, spectroscopic, and electrochemical properties of
      selected members were also studied. The present work is trying to enrich metal
      containing supramolecular chemistry through the inclusion of well-characterized
      quadruply bonded Mo-Mo units into the structures, which can widen the prospect of
      additional electronic functionality, thereby leading to novel properties.

PMID- 21082848
TI  - Conformational analysis of o-phenylenes: helical oligomers with frayed ends.
AB  - The o-phenylenes represent a fundamental class of conjugated polymers that,
      unlike the isomeric p-phenylenes, should exhibit rich conformational behavior.
      Recently, we reported the synthesis and characterization of a series of o
      phenylene oligomers featuring unusual electronic properties, including
      surprisingly long-range delocalization as measured by UV-vis spectroscopy and
      hypsochromic shifts in fluorescence maxima with increasing length. To rationalize
      these properties, we hypothesized that the oligomers predominantly assume a
      stacked helical conformation in solution. This assertion, however, was supported
      by only indirect evidence. Here we present a thorough investigation of the
      conformational behavior of this series of o-phenylenes by dynamic NMR
      spectroscopy and computational chemistry. EXSY experiments, in combination with
      other two-dimensional NMR techniques, provided full (1)H chemical shift
      assignments for at least the two most prevalent conformers for each member of the
      series (hexamer to dodecamer). GIAO density functional theory calculations were
      then used to relate the NMR data to specific molecular geometries. We have found
      that the o-phenylenes do indeed assume stacked helical conformations with
      disorder occurring at the ends. Thus, the o-phenylene motif appears to have great
      potential as a means to organize arenes into predictable three-dimensional
      arrangements. Our results also illustrate the power of (1)H NMR GIAO predictions
      in the solution-phase conformational analysis of oligomers, particularly those
      with a high density of aromatic subunits.

PMID- 21082849
TI  - Experimental and mechanistic investigation of an iodomalonic acid-based Briggs
      Rauscher oscillator and its perturbations by resorcinol.
AB  - Classic Briggs-Rauscher oscillators use malonic acid (MA) as a substrate. The
      first organic product is iodomalonic acid. Iodomalonic acid (IMA) can serve as a
      substrate also; thus, the first product in that case is diiodomalonic acid
      (I(2)MA). Nonoscillating iodination kinetics can be followed by absorbance at 462
      nm in acidic KIO(3) so long as IMA is in substantial excess over [I(2)]. At 25 
      degrees C, simulations lead to the two most important rate laws, and related rate
      constant estimates are reported. I(2)MA eventually decomposes by unknown
      processes, but I(2), O(2), H(2)O(2), and Mn(2+) speed up that decomposition,
      liberating most of the iodine back to the solution. Resorcinol is an effective
      inhibitor of oscillations both in MA oscillators and in IMA oscillators. Response
      of an IMA oscillator to varying amounts of resorcinol is shown herein and is
      similar to that for MA-based oscillators. The inhibitory effect of resorcinol is
      diminished by addition of IMA to a MA-based oscillator. The iodination reaction
      between IMA and resorcinol is too slow (0.043 M(-1) s(-1)) to account for the
      decreased inhibitory effectiveness of resorcinol. Rather, the decomposition of
      I(2)MA is responsible for the inhibition decrease.

PMID- 21082850
TI  - Reaction pathway of methylenation of carbonyl compounds with
      bis(iodozincio)methane.
AB  - About 40 years have passed since methylene dizinc reagent was discovered as a
      substitute for Wittig reagent. Density functional theory (DFT) calculations have
      been performed to understand the reaction pathways of methylenation of carbonyl
      compounds with bis(iodozincio)methane. The present computational/theoretical
      study concluded that the methylenation reaction with gem-dizinc reagent proceeds
      as a two-step reaction, that is, methylene addition (RDS) and olefination. In the
      first step, the nucleophilic attack of the CH2 group enhanced by two Zn proceeds
      under the assistance of the electrophilic activation of the carbonyl group with
      the Zn atom. In the second step, the olefination is facilitated by both Zn atoms
      of the gem-dizinc reagent without an electron transfer process.

PMID- 21082851
TI  - Mechanism of acid-catalyzed hydrolysis of formamide from cluster-continuum model
      calculations: concerted versus stepwise pathway.
AB  - The acid-catalyzed hydrolysis of formamide in aqueous solutions was investigated
      by ab initio calculations. Solvent effects on the hydrolysis reaction were
      reasonably considered by the cluster-continuum model with explicit water
      molecules in the first solvation shell, and the selection of hydration cluster
      plays an important role in reliable estimation of thermodynamic values for the
      hydrolysis reaction. Possible concerted and stepwise mechanisms of the O
      protonated and N-protonated pathways were investigated by extensive calculations.
      On the basis of unbiased theoretical treatments on all plausible pathways, the O
      protonated stepwise pathway was shown to be the favored mechanism, and the
      predicted activation free energies for the rate-determining step and the breaking
      of the C-N bond are 21.8 and 9.4 kcal/mol by B3LYP, respectively. The present
      results show good agreement with experiment and provide a complete description of
      the acid-catalyzed hydrolysis of formamide.

PMID- 21082852
TI  - Construction of the tricyclic 5-7-6 scaffold of fungi-derived diterpenoids. Total
      synthesis of (+/-)-heptemerone G and an approach to Danishefsky's intermediate
      for guanacastepene A synthesis.
AB  - An efficient and operationally simple synthesis of the neodolestane diterpenoids
      (+/-)-heptemerone G and (+/-)-guanacastepene A is reported. The common tricyclic
      scaffold (+/-)-4 was prepared from 2-methylcyclopent-2-en-1-one via 23 isolated
      intermediates in 5.1% yield. The key features include a novel annulation sequence
      combining tandem conjugate addition, methylenation, and metathesis reaction and
      completely diastereoselective transformation of the azulene derivative 23 into
      rings AB building block 32. Stereochemistry of alkylation of both saturated trans
      azulene enolate 38 and its alpha,beta-unsaturated counterpart 48 was examined.
      Rather surprisingly, a different facial selectivity was recorded. Several
      synthetic methods were modified or developed, including an alternative
      methodology for the Wharton-type rearrangement, ketalization of epimerizable
      ketone under mild conditions, and efficient alkylation of a ketone via its
      kinetic enolate.

PMID- 21082854
TI  - Competitive mechanistic pathways for green-to-red photoconversion in the
      fluorescent protein Kaede: a computational study.
AB  - In Kaede, a new class of fluorescent protein, dramatic changes of photophysical
      and chemical properties by UV illumination have been observed in which the color
      of fluorescence is irreversibly altered from green to red. Unusual photoinduced
      peptide backbone cleavage resulting in extending pi-conjugation of the
      chromophore takes place. Two mechanistic pathways (E1 and E2 mechanisms)
      involving the N-C(alpha) bond cleavage at His62 and deprotonation at C(beta) by
      Glu212 have been proposed. Here several possible pathways are explored with
      explicit consideration of protein environment by ONIOM(B3LYP:AMBER) calculations.
      The results reject the concerted E2 pathway. Instead, the stepwise E1 and new
      E1cb mechanisms are suggested to occur and may compete with each other in the
      electronic ground state. Absorption for the green- and red-type chromophore in
      vacuum and within the Kaede protein matrix was studied.

PMID- 21082855
TI  - Vibrational energy transfer between carbon nanotubes and nonaqueous solvents: a
      molecular dynamics study.
AB  - We report molecular dynamics (MD) simulation of energy exchange between single
      walled carbon nanotubes (CNTs) and two aprotic solvents, acetonitrile and
      cyclohexane. Following our earlier study of hydrated CNTs, we find that the time
      scales and molecular mechanisms of the energy transfer are largely independent of
      the nature of the surrounding medium, and therefore, should hold for other media
      including polymer matrices and DNA. The vibrational energy exchange between CNT
      and solvents exhibits two time-scales. Over half of the energy is transferred in
      less than one picosecond, indicating that the dominant exchange mechanism is
      inertial relaxation. It occurs by collisions of solvent molecules with CNT walls,
      facilitated by the short-range Lennard-Jones interaction. Additional several
      picoseconds are required for the remainder of the vibrational energy exchange,
      corresponding to the diffusive relaxation mechanism and involving collective
      molecular motions. The faster stage of the CNT-solvent energy exchange occurs on
      the same time-scale, and therefore, competes with the vibrational energy
      relaxation inside CNTs. The energy exchange time-scales are significantly
      influenced by the arrangement of solvent molecules inside CNTs. Generally, the
      effects of confinement on the dynamics can be rationalized by analysis of the
      solvent structure. For the same CNT diameter, the extent of the confinement
      effect strongly depends on the size of the solvent molecules. Icelike properties
      in water seen in small CNTs disappear in CNTs with intermediate diameters. In
      acetonitrile and cyclohexane, medium size CNTs still show strong confinement
      effects. Rotational motions of acetonitrile molecules are inhibited, and the
      cyclohexane density is dramatically decreased. The disbalance between the local
      temperatures of the inside and outside regions of the solvent equilibrates
      through a tube-mediated interaction, rather than by a direct coupling between the
      two solvent subsystems. In all cases, the CNT-solvent energy transfer is mediated
      by slow motions in the frequency range of CNT radial breathing modes.

PMID- 21082856
TI  - High-nuclearity Pt-Tl-Fe complexes: structural, electrochemistry, and
      spectroelectrochemistry studies.
AB  - A series of heteropolynuclear Pt-Tl-Fe complexes have been synthesized and
      structurally characterized. The final structures strongly depend on the geometry
      of the precursor and the Pt/Tl ratio used. Thus, the anionic heteroleptic cis
      configured [cis-Pt(C(6)F(5))(2)(C=CFc)(2)](2-) and [Pt(bzq)(C=CFc)(2)](-) (Fc =
      ferrocenyl) complexes react with Tl(+) to form discrete octanuclear
      (PPh(3)Me)(2)[{trans,cis,cis-PtTl(C(6)F(5))(2)(C=CFc)(2)}(2)] (1),
      [PtTl(bzq)(C=CFc)(2)](2) (5; bzq = benzoquinolate), and decanuclear
      [trans,cis,cis-PtTl(2)(C(6)F(5))(2)(C=CFc)(2)](2) (3) derivatives, stabilized by
      both Pt(II)...Tl(I) and Tl(I)...eta(2)(alkynyl) bonds. By contrast, Q(2)[trans
      Pt(C(6)F(5))(2)(C=CFc)(2)] (Q = NBu(4)) reacts with Tl(+) to give the one
      dimensional (1-D) anionic [(NBu(4)){trans,trans,trans
      PtTl(C(6)F(5))(2)(C=CFc)(2)}](n) (2) and neutral [trans,trans,trans
      PtTl(2)(C(6)F(5))(2)(C=CFc)(2)](n) (4) polymeric chains based on [PtFc(2)](2-)
      platinate fragments and Tl(+) (2) or [Tl...Tl](2+) (4) units, respectively,
      connected by Pt(II)...Tl(I) and secondary weak kappa-eta(1) (2) or eta(2) (4)
      alkynyl...Tl(I) bonding. The formation of 1-4 is reversible, and thus treatment
      of neutral 3 and 4 with PPh(3)MeBr causes the precipitation of TlBr, returning
      toward the formation of the anionic 1 and 2' (Q = PPh(3)Me). Two slightly
      different pseudopolymorphs were found for 2', depending on the crystallization
      solvent. Finally, the reaction of the homoleptic [Pt(C=CFc)(4)](2-) with 2 equiv
      of Tl(+) affords the tetradecanuclear sandwich type complex
      [Pt(2)Tl(4)(C=CFc)(8)] (6). Electrochemical, spectroelectrochemical, and
      theoretical studies have been carried out to elucidate the effect produced by the
      interaction of the Tl(+) with the Pt-C=CFc fragments. The cyclic voltammetry (CV)
      and differential pulse voltammetry (DPV) of 1-5 reveal that, in general,
      neutralization of the anionic fragments increases the stability of the fully
      oxidized species and gives higher E(1/2) (Fc) values than those observed in their
      precursors, increasing with the number of Pt-Tl bonding interactions. However,
      the electronic communication between Fc groups is reduced or even lost upon Tl(+)
      coordination, as confirmed by electrochemical (CVs and DPVs voltammograms, 1-5)
      and spectroelectrochemical (UV-vis-NIR, 2-4) studies. Complexes 2 and 4 still
      display some electronic interaction between the Fc groups, supported by the
      presence of an IVCT band in their UV-vis-NIR spectra of oxidized species and
      additional comparative DFT calculations with the precursor [trans
      Pt(C(6)F(5))(2)(C=CFc)(2)](2-) and complex 3.

PMID- 21082857
TI  - High-efficiency solid-state dye-sensitized solar cells: fast charge extraction
      through self-assembled 3D fibrous network of crystalline TiO2 nanowires.
AB  - Herein, we present a novel morphology for solid-state dye-sensitized solar cells
      based on the simple and straightforward self-assembly of nanorods into a 3D
      fibrous network of fused single-crystalline anatase nanowires. This architecture
      offers a high roughness factor, significant light scattering, and up to several
      orders of magnitude faster electron transport to reach a near-record-breaking
      conversion efficiency of 4.9%.

PMID- 21082858
TI  - Synthesis and photophysical properties of N-fused tetraphenylporphyrin
      derivatives: near-infrared organic dye of [18]annulenic compounds.
AB  - A variety of N-fused porphyrin derivatives were prepared and their photophysical
      properties were investigated. Although intact N-fused tetraarylporphyrins showed
      almost no emission, introduction of electron-withdrawing groups such as a nitro
      group and a cyano group on the macrocycles caused significant refinements in
      their emission efficiency. Long emission wavelengths (900-1000 nm) as well as
      fairly large Stokes shifts (~1200 cm(-1)) are exceptionally unique photophysical
      properties among [18]annulenic compounds, which could be rationalized by the
      excited state intramolecular proton transfer (ESIPT) process. Relatively weak
      emission quantum yields (~5.0 * 10(-4)) and unusually short S(1) state lifetimes
      (~13.5 ps) are in good agreement with the ESIPT process. The solvent and
      substituent effects on the photophysical properties are also discussed in
      conjunction with the theoretical studies, where the mesityl groups at the meso
      positions play a unique role.

PMID- 21082859
TI  - Antitumor activity of capsaicin on human colon cancer cells in vitro and colo 205
      tumor xenografts in vivo.
AB  - Capsaicin was reported to inhibit cancer cell growth. The aim of this study was
      to evaluate the antitumor potential of capsaicin by studying antitumor activity
      in vitro as well as in vivo. The in vitro studies are to examine the effects of
      capsaicin on human colon cancer colo 205 cells after exposure to capsaicin. The
      results showed that capsaicin induced cytotoxic effects in a time- and dose
      dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but
      decreased the level of mitochondrial membrane potential (DeltaPsi(m)) in colo 205
      cells. Data from Western blotting analysis indicated that the levels of Fas,
      cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin
      decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the
      levels of pro-apoptotic proteins such as Bax. Capsaicin-induced apoptosis in colo
      205 cells was also done through the activations of caspase-8, -9 and -3. In vivo
      studies in immunodeficient nu/nu mice bearing colo 205 tumor xenografts showed
      that capsaicin effectively inhibited tumor growth. The potent in vitro and in
      vivo antitumor activities of capsaicin suggest that capsaicin might be developed
      for the treatment of human colon cancer.

PMID- 21082860
TI  - Oolong tea theasinensins attenuate cyclooxygenase-2 expression in
      lipopolysaccharide (LPS)-activated mouse macrophages: structure-activity
      relationship and molecular mechanisms.
AB  - Oolong tea theasinensins are a group of tea polyphenols different from green tea
      catechins and black tea theaflavins. The present study reports the inhibitory
      effects of oolong tea theasinensins on the expression of cyclooxygenase-2 (COX-2)
      and underlying molecular mechanisms in lipopolysaccharide (LPS)-activated murine
      macrophage RAW264 cells. The structure-activity data revealed that the galloyl
      moiety of theasinensins played an important role in the inhibitory actions.
      Theasinensin A, a more potent inhibitor, caused a dose-dependent inhibition of
      mRNA, protein, and promoter activity of COX-2. An electrophoretic mobility shift
      assay (EMSA) revealed that theasinensin A reduced the complex of NF-kappaB- and
      AP-1-DNA in the promoter of COX-2. Signaling analysis demonstrated that
      theasinensin A attenuated IkappaB-alpha degradation, nuclear p65 accumulation,
      and c-Jun phosphorylation. Furthermore, theasinensin A suppressed the
      phosphorylation of MAPKs, IkappaB kinase alpha/beta (IKKalpha/beta), and TGF-beta
      activated kinase (TAK1). These data demonstrated that the down-regulation of TAK1
      mediated MAPKs and NF-kappaB signaling pathways might be involved in the
      inhibition of COX-2 expression by theasinensin A. These findings provide the
      first molecular basis for the anti-inflammatory properties of oolong tea
      theasinensins.

PMID- 21082861
TI  - Identification of the botanical origin of raw spirits produced from rye, potato,
      and corn based on volatile compounds analysis using a SPME-MS method.
AB  - Determination of the botanical origin of raw spirit used for alcoholic beverage
      production is of great importance for rectifying units, control laboratories, and
      proper product labeling. Raw spirit samples (138) produced from rye, corn, and
      potato were analyzed using a solid phase microextraction-mass spectrometry (SPME
      MS) method, which involved volatiles preconcentration by SPME with subsequent
      volatile fraction characterization by MS without particular compounds separation
      by GC. Obtained data were treated using principal component analysis and linear
      discriminant analysis (LDA) to test the possibility of sample classification.
      SPME sampling conditions allowed rapid extraction in 2 min at 50  degrees C using
      a carboxen/divinylbenzene/polydimethylsiloxane fiber, followed by rapid MS
      analysis. Use of LDA made possible the classification of raw spirits based on the
      material they were produced from. The classification ability of the developed
      SPME-MS method was 100%, whereas its prediction ability was 96%.

PMID- 21082862
TI  - Benzimidazol-2-ylidene gold(I) complexes are thioredoxin reductase inhibitors
      with multiple antitumor properties.
AB  - Gold(I) complexes such as auranofin have been used for decades to treat symptoms
      of rheumatoid arthritis and have also demonstrated a considerable potential as
      new anticancer drugs. The enzyme thioredoxin reductase (TrxR) is considered as
      the most relevant molecular target for these species. The here investigated
      gold(I) complexes with benzimidazole derived N-heterocyclic carbene (NHC) ligands
      represent a promising class of gold coordination compounds with a good stability
      against the thiol glutathione. TrxR was selectively inhibited by in comparison to
      the closely related enzyme glutathione reductase, and all complexes triggered
      significant antiproliferative effects in cultured tumor cells. More detailed
      studies on a selected complex revealed a distinct pharmacodynamic profile
      including the high increase of reactive oxygen species formation, apoptosis
      induction, strong effects on cellular metabolism (related to cell surface
      properties, respiration, and glycolysis), inhibition of mitochondrial respiration
      and activity against resistant cell lines.

PMID- 21082863
TI  - Batch-fabrication of cantilevered magnets on attonewton-sensitivity mechanical
      oscillators for scanned-probe nanoscale magnetic resonance imaging.
AB  - We have batch-fabricated cantilevers with ~100 nm diameter nickel nanorod tips
      and force sensitivities of a few attonewtons at 4.2 K. The magnetic nanorods were
      engineered to overhang the leading edge of the cantilever, and consequently the
      cantilevers experience what we believe is the lowest surface noise ever achieved
      in a scanned probe experiment. Cantilever magnetometry indicated that the tips
      were well magnetized, with a <= 20 nm dead layer; the composition of the dead
      layer was studied by electron microscopy and electron energy loss spectroscopy.
      In what we believe is the first demonstration of scanned probe detection of
      electron-spin resonance from a batch-fabricated tip, the cantilevers were used to
      observe electron-spin resonance from nitroxide spin labels in a film via force
      gradient-induced shifts in cantilever resonance frequency. The magnetic field
      dependence of the magnetic resonance signal suggests a nonuniform tip
      magnetization at an applied field near 0.6 T.

PMID- 21082864
TI  - Identification and synthesis of novel inhibitors of acetyl-CoA carboxylase with
      in vitro and in vivo efficacy on fat oxidation.
AB  - Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat
      utilization and their inhibition is considered to improve aspects of the
      metabolic syndrome. To identify pharmacological inhibitors of ACC1/2, a high
      throughput screen was performed which resulted in the identification of the lead
      compound 3 ( Gargazanli , G. ; Lardenois , P. ; Frost , J. ; George , P. Patent
      WO9855474 A1, 1998 ) as a moderate selective ACC2 inhibitor. Optimization of 3
      led to 4m ( Zoller , G. ; Schmoll , D. ; Mueller , M. ; Haschke , G. ; Focken ,
      I. Patent WO2010003624 A2, 2010 ) as a submicromolar dual ACC1/2 inhibitor of the
      rat and human isoforms. 4m possessed favorable pharmacokinetic parameters. This
      compound stimulated fat oxidation in vivo and reduced plasma triglyceride levels
      in a rodent model after subchronic administration. 4m is a suitable tool compound
      for the elucidation of the pharmacological potential of ACC1/2 inhibition.

PMID- 21082867
TI  - A practical guide for estimating rates of heterolysis reactions.
AB  - Chemists are well trained to recognize what controls relative reactivities within
      a series of compounds. Thus, it is well-known how the rate of ionization of R-X
      is affected by the stabilization of the carbocation R(+), the nature of the
      leaving group X(-), or the solvent ionizing power. On the other hand, when asked
      to estimate the half-life of the ionization of a certain substrate in a certain
      solvent, most chemists resign. This question, however, is crucial in daily
      laboratory practice. Can a certain substrate R-X be handled in alcoholic or
      aqueous solution without being solvolyzed? Can a biologically active tertiary
      amine or azole be released by ionization of a quaternary ammonium ion? In this
      Account, we describe a straightforward means of addressing such experimental
      concerns. A semiquantitative answer to these questions is given by the
      correlation equation log k(25  degrees C) = s(f)(N(f) + E(f)), in which
      carbocations R(+) are characterized by the electrofugality parameter E(f), and
      leaving groups X(-) in a certain solvent are characterized by the nucleofugality
      parameter N(f) and the nucleofuge-specific sensitivity parameter s(f). As s(f) is
      typically around 1 (0.8 < s(f) < 1.2), ionization half-lives of around 1 h at 25 
      degrees C can be expected when E(f) + N(f) = -4. This correlation equation is
      formally analogous to the linear free energy relationship that was used to derive
      the most comprehensive nucleophilicity and electrophilicity scales presently
      available (Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.;
      Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. Reference Scales
      for the Characterization of Cationic Electrophiles and Neutral Nucleophiles. J.
      Am. Chem. Soc. 2001, 123, 9500-9512). By subjecting 628 solvolysis rate constants
      k(25  degrees C) for different benzhydryl derivatives (aryl(2)CH-X) to a least
      squares minimization on the basis of the correlation equation, we obtained and
      tabulate here (i) the electrofugality parameters E(f) for 39 benzhydrylium ions
      and (ii) the nucleofuge-specific parameters N(f) and s(f) for 101 combinations of
      common leaving groups and solvents. We show that the E(f) parameters of the
      reference electrofuges can be used to determine N(f) and s(f) for almost any
      combination of leaving group and solvent. The nucleofuge-specific parameters of
      the reference systems can analogously be used to derive the electrofugalities
      E(f) of other types of carbocations. While it has long been recognized that good
      nucleophiles are not necessarily poor nucleofuges, it is now reported that there
      is also no general inverse relationship between electrophilicity and
      electrofugality. Although more electrophilic methyl- and methoxy-substituted
      benzhydrylium ions are generally weaker electrofuges, the inverse relationship
      between electrophilicity and electrofugality breaks down in the series of amino
      substituted benzhydrylium ions. Because neither differential solvation of the
      carbocations nor steric effects are explicitly considered by this treatment,
      predictions for substrates not belonging to the benzhydrylium series are only
      reliable within a factor of 10. This is hardly acceptable to physical organic
      chemists, who are used to high precision within narrow groups of compounds. The
      synthetic chemist, however, who is seeking orientation in a reactivity range of
      25 orders of magnitude, might appreciate the simplicity of this approach, which
      only requires considering the sum E(f) + N(f) or consulting our summary graphs.

PMID- 21082865
TI  - Proton-coupled electron flow in protein redox machines.

PMID- 21082869
TI  - Stroke? Localized, otogenic meningitis!
AB  - We report the case of a patient admitted with aphasia, treated for a stroke.
      Subsequently, it was revealed that the symptoms were caused by complicated otitis
      media with localized meningitis. This case draws attention to the possible
      intracranial spread of infection when neurological symptoms occur in a patient
      with otitis media.

PMID- 21082870
TI  - Contrast-enhanced MRI of the inner ear after intratympanic injection of meglumine
      gadopentetate or gadodiamide hydrate.
AB  - CONCLUSION: The degree of contrast enhancement of the cochlea after intratympanic
      administration of meglumine gadopentetate (Gd-DTPA) or gadodiamide hydrate (Gd
      DTPA-BMA) varies widely among patients with inner ear diseases. There was no
      morphological change in the stria vascularis after Gd-DTPA or Gd-DTPA-BMA was
      placed on the round window of guinea pigs. OBJECTIVES: We investigated the degree
      of contrast enhancement of the inner ear after intratympanic administration of
      ionized and nonionized gadolinium (Gd) contrast agents in patients with inner ear
      diseases. The inner ear toxicities of these agents were investigated in guinea
      pigs. METHODS: 3D-FLAIR MRI was conducted 1 day after the intratympanic injection
      of eightfold-diluted Gd-DTPA or Gd-DTPA-BMA in 73 patients with inner ear
      diseases. Gd enhancement of the basal turn of the cochlea was evaluated as the
      signal intensity (SI) ratio between the affected and nonaffected sides. In guinea
      pigs, nondiluted Gd-DTPA, Gd-DTPA-BMA or saline was placed on the round window
      for 1 h and the stria vascularis was observed using electron microscopy. RESULTS:
      The SI ratio ranged from 1.5 to 16.5 in the Gd-DTPA group and from 2.5 to 21 in
      the Gd-DTPA-BMA group. Electron microscopy showed no significant differences in
      the stria vascularis of guinea pigs in any of the groups.

PMID- 21082871
TI  - Swedish rehabilitation professionals' perspectives on work ability assessments in
      a changing sickness insurance system.
AB  - PURPOSE: Changes in the Swedish sickness insurance system shifts focus from
      return-to-work to labour market reintegration. This article analyses Swedish
      rehabilitation professionals' perspectives on how the changed regulations affect
      practice, with a special focus on work ability assessments. METHODS: Two groups
      of representatives (n = 15) from organizations involved in rehabilitation and
      return-to-work met at seven occations. The groups worked with a tutor with a
      problem-based approach to discuss how their practice is influenced by the changed
      regulations. The material was analysed inductively using qualitative content
      analysis. RESULTS: The new regulations require developed cooperation among
      insurance, health care, employers and occupational health care; however, these
      demands are not met in practice. In work ability assessments, several flaws
      regarding competence and cooperation are identified. An increasing number of
      people previously assessed as work disabled are required to participate in labour
      market reintegration, which puts demands on professionals to engage in
      motivational activities, although this is perceived as hopeless due to the
      group's lack of employability. CONCLUSIONS: The possibility for employers to
      sidestep their responsibility has increased with changed regulations. The overall
      lack of cooperation between relevant actors and the lack of relevant competence
      undermine the ambitions of activation and reintegration in the reform.

PMID- 21082872
TI  - Patients' experience post-lumbar fusion regarding back problems, recovery and
      expectations in terms of the International Classification of Functioning,
      Disability and Health.
AB  - PURPOSE: To describe within the context of the International Classification of
      Functioning, Disability and Health (ICF), patient's experiences post-lumber
      fusion regarding back problems, recovery and expectations of rehabilitation and
      to contrast with the content of outcome measures and the ICF low back pain (LBP)
      core sets. METHODS: The study has a cross-sectional and retrospective design and
      involves 20 lumbar fusion patients. Using the ICF, qualitative content analysis
      of semi-structured interviews 3-6 months post-surgery was performed. This was
      compared with the ICF related content of the Oswestry Disability Index (ODI),
      Medical Outcome Study Short Form 36 (SF-36), European Quality of Life
      Questionnaire (EQ5D) and the ICF LBP core sets. RESULTS: Patient's experiences
      were most frequently linked to psychological, sensory, neuromusculoskeletal and
      movement related body function chapters of the ICF. The most frequently linked
      categories of activity and participation were mobility, domestic activities,
      family relationships, work, recreation and leisure. Environmental factors
      frequently linked were the use of analgesics, walking aids, family support,
      social security systems, health care systems and labour market employment
      services. CONCLUSIONS: This study highlights important ICF related aspects of
      patient's experiences post-lumber fusion. The use of the comprehensive ICF core
      sets is recommended in conjunction with ODI, SF-36 and the EQ5D for a broader
      analysis of patient outcomes post-lumbar fusion.

PMID- 21082873
TI  - Reliability and structural validity of an assessment of occupational value.
AB  - This study evaluated the psychometric properties of the American English (Am.
      Eng.) version of the Occupational Value Assessment with predefined items (OVal
      pd). The OVal-pd is a 26-item Likert-like questionnaire designed to assess the
      construct of occupational value as framed within the Value and Meaning in
      Occupations model (ValMO). Following a translation from the Swedish OVal-pd, 277
      randomly selected graduate and undergraduate students from a public university in
      the northwestern United Stated completed the Am. Eng. OVal-pd. Test-retest and
      internal consistency reliability coefficients were very good utilizing an
      improved 22-item version of the OVal-pd. The structural validity of the 22-item
      Am. Eng. OVap-pd was partly confirmed through exploratory factor analysis. The
      scale was found to assess a one-dimensional value construct supporting the ValMO
      model, consisting of components clearly reflective of self-reward and concrete
      value. Exploratory factor analysis results were equivocal with regard to the
      symbolic dimension of the ValMO model as assessed by the OVal-pd. Discussion
      suggests the refinement of both the OVal-pd and ValMO model in the light of
      present and related empirical findings.

PMID- 21082874
TI  - Y-shaped endoscopic bilateral metal stent placement for malignant hilar biliary
      obstruction: prospective long-term study.
AB  - OBJECTIVE: Although still controversial, bilateral stenting may be the best
      option for palliative drainage of malignant hilar biliary obstruction. The aim of
      our study was to evaluate the technical and clinical efficacies of endoscopic
      bilateral metal stenting using a biliary Y-stent for the management of malignant
      hilar obstruction. MATERIAL AND METHODS: This prospective, uncontrolled study
      included 30 consecutive patients with unresectable malignant hilar strictures in
      whom we intended to perform endoscopic bilateral stent-in-stent deployment using
      a biliary Y-stent. After deployment of the Y-stent across the hilar stricture, a
      conventional biliary metal stent was inserted in a Y-configuration in which it
      traversed the wider-mesh central portion of the Y-stent to enter the opposite
      hepatic lobe. RESULTS: Bilateral metal stenting using a Y-stent was successful in
      26 of 30 patients (86.7%), and successful drainage was achieved in all 26
      patients (100%). Early complications occurred in 3 patients (cholangitis, 1;
      cholecystitis, 2) without procedure-related mortality. As late complications
      during the follow-up period (median, 176 days; range, 70-473 days), stent
      occlusion occurred in 10 of 26 patients (38.5%). Four patients were managed with
      the insertion of a plastic stent through the occluded metal stent, and the
      remaining patients were treated with percutaneous biliary drainage. The median
      survival and stent patency were 176 days and 140 days, respectively. CONCLUSIONS:
      Y-shaped endoscopic bilateral stenting using a Y-stent appears to be a feasible
      and effective method with high technical success and low stent-related
      complications for palliation of unresectable malignant hilar biliary obstruction.

PMID- 21082875
TI  - Bilateral same-session ureteroscopy for treatment of ureteral calculi: critical
      analysis of risk factors.
AB  - OBJECTIVE: To determine factors affecting the success of bilateral same-session
      ureteroscopy (BSU) in the treatment of ureteral calculi. MATERIAL AND METHODS:
      From January 2003 to December 2008, BSU was carried out in 89 patients (178 renal
      units). A successful outcome was considered when both ureters were free of stones
      without intraoperative complications. Stone-free rate was evaluated with a kidney
      ureter-bladder plain X-ray or non-contrast computed tomography. Factors
      interfering with successful completion of BSU were tested using univariate (chi
      squared test and t test) and multivariate (logistic regression) analyses. Data on
      unilateral ureteroscopy for the treatment of multiple ureteral calculi carried
      out in 105 patients during the same period were compared with BSU. RESULTS:
      Intraoperative complications were recorded in 11 procedures (6.2%) in the form of
      ureteral perforation in three and mucosal injury in eight. After BSU, 153 renal
      units were stone free (86%) as 17 had residual fragments, stones migrated to the
      kidney in six and failure was encountered in two. A successful outcome was
      observed in 62 patients (70%). Stone impaction, stones located in the proximal
      ureter and stone surface area were the significant risk factors for unsuccessful
      BSU (relative risks 3.6, 3.3 and 1.47, respectively). Compared with unilateral
      ureteroscopy, no difference were found with regard to complication rate (6.7%, p
      = 0.5) or stone-free rate (80%, p = 0.2). CONCLUSIONS: Bilateral same-session
      ureteroscopy is a safe and effective procedure in the management of bilateral
      ureteral stones. Proximal ureteral calculi, large and impacted stones carry the
      highest risk of unsuccessful results.

PMID- 21082868
TI  - Safety of anacetrapib in patients with or at high risk for coronary heart
      disease.
AB  - BACKGROUND: Anacetrapib is a cholesteryl ester transfer protein inhibitor that
      raises high-density lipoprotein (HDL) cholesterol and reduces low-density
      lipoprotein (LDL) cholesterol. METHODS: We conducted a randomized, double-blind,
      placebo-controlled trial to assess the efficacy and safety profile of anacetrapib
      in patients with coronary heart disease or at high risk for coronary heart
      disease. Eligible patients who were taking a statin and who had an LDL
      cholesterol level that was consistent with that recommended in guidelines were
      assigned to receive 100 mg of anacetrapib or placebo daily for 18 months. The
      primary end points were the percent change from baseline in LDL cholesterol at 24
      weeks (HDL cholesterol level was a secondary end point) and the safety and side
      effect profile of anacetrapib through 76 weeks. Cardiovascular events and deaths
      were prospectively adjudicated. RESULTS: A total of 1623 patients underwent
      randomization. By 24 weeks, the LDL cholesterol level had been reduced from 81 mg
      per deciliter (2.1 mmol per liter) to 45 mg per deciliter (1.2 mmol per liter) in
      the anacetrapib group, as compared with a reduction from 82 mg per deciliter (2.1
      mmol per liter) to 77 mg per deciliter (2.0 mmol per liter) in the placebo group
      (P<0.001)--a 39.8% reduction with anacetrapib beyond that seen with placebo. In
      addition, the HDL cholesterol level increased from 41 mg per deciliter (1.0 mmol
      per liter) to 101 mg per deciliter (2.6 mmol per liter) in the anacetrapib group,
      as compared with an increase from 40 mg per deciliter (1.0 mmol per liter) to 46
      mg per deciliter (1.2 mmol per liter) in the placebo group (P<0.001)--a 138.1%
      increase with anacetrapib beyond that seen with placebo. Through 76 weeks, no
      changes were noted in blood pressure or electrolyte or aldosterone levels with
      anacetrapib as compared with placebo. Prespecified adjudicated cardiovascular
      events occurred in 16 patients treated with anacetrapib (2.0%) and 21 patients
      receiving placebo (2.6%) (P = 0.40). The prespecified Bayesian analysis indicated
      that this event distribution provided a predictive probability (confidence) of
      94% that anacetrapib would not be associated with a 25% increase in
      cardiovascular events, as seen with torcetrapib. CONCLUSIONS: Treatment with
      anacetrapib had robust effects on LDL and HDL cholesterol, had an acceptable side
      effect profile, and, within the limits of the power of this study, did not result
      in the adverse cardiovascular effects observed with torcetrapib. (Funded by Merck
      Research Laboratories; ClinicalTrials.gov number, NCT00685776.).

PMID- 21082877
TI  - In vitro connector research.

PMID- 21082879
TI  - Preexisting antibodies against pandemic 2009 influenza A (H1N1) virus in Taiwan.

PMID- 21082878
TI  - Cryptococcal antigen screening for patients initiating antiretroviral therapy:
      time for action.

PMID- 21082882
TI  - Do stem cell-derived islets represent a commercially viable treatment for Type 1
      and 2 diabetes?

PMID- 21082883
TI  - International Regenerative Medicine Legislative Day.

PMID- 21082885
TI  - Improved muscle regeneration by combining VEGF with IGF1.

PMID- 21082886
TI  - Cell therapies and Parkinson's disease: where next? Interviewed by Emily Culme
      Seymour.
AB  - Dr Roger A Barker is a University Reader in Clinical Neuroscience and Honorary
      Consultant in Neurology at the Addenbrooke's Hospital. He trained at Oxford and
      in London and has been in his current position for 10 years, having completed an
      MRC Clinician Scientist Fellowship prior to this. His main interests are in the
      neurodegenerative disorders of the nervous system, in particular Parkinson's
      disease and Huntington's disease. Dr Barker combines basic research investigating
      cell therapies to treat these conditions, with clinically based work on defining
      the natural history and heterogeneity of both diseases. He is a member of the
      CURE PD Research Advisory Panel and the MRC Stem Cell Liaison Committee. He is a
      member of the Regenerative Medicine editorial board and co-editor-in-chief of the
      journals ACNR and the Journal of Neurology.

PMID- 21082887
TI  - Regenerative medicine in Brazil: small but innovative.
AB  - AIMS: Although Brazil has received attention for conducting one of the world's
      largest stem cell clinical trials for heart disease, little has been published
      regarding Brazil's regenerative medicine (RM) sector. Here we present a
      comprehensive case study of RM in Brazil, including analysis of the current
      activity, the main motivations for engaging in RM and the remaining challenges to
      development in this field. METHODS: Our case study is primarily based on semi
      structured interviews with experts on RM in Brazil, including researchers,
      policymakers, clinicians, representatives of firms and regulators. RESULTS:
      Driven by domestic health needs and strategic government support, Brazil is
      producing innovative RM research, particularly for clinical research in
      cardiology, orthopedics, diabetes and neurology. We describe the main RM research
      currently taking place in Brazil, as well as some of the economic, regulatory and
      policy events that have created a favorable environment for RM development.
      Brazilian RM researchers need to overcome several formidable challenges to
      research: research funding is inconsistent, importation of materials is costly
      and slow, and weak linkages between universities, hospitals and industry impede
      translational research. CONCLUSIONS: Although Brazil's contribution to the RM
      sector is small, its niche emphasis on clinical applications may become of global
      importance, particularly if Brazil manages to address the challenges currently
      impinging on RM innovation.

PMID- 21082888
TI  - Simulation of an in vitro niche environment that preserves conjunctival
      progenitor cells.
AB  - AIM: To evaluate a serum-free system where mitotically active subconjunctival
      fibroblasts were co-cultured with conjunctival epithelial cells to mimic a niche
      environment for conjunctival progenitor cells. METHODS: Human conjunctival
      epithelial cells were expanded in vitro and evaluated for their colony-forming
      efficiency and clonal ability. The cells were then transferred to a serum-free co
      culture system and cultured in the presence of mitotically active subconjunctival
      fibroblasts (human conjunctival epithelial cells and human bulbar subconjunctival
      fibroblasts [HCEC-HCF]). Cells were evaluated by Ki67 staining, total colony
      forming efficiency and the number of colonies with a surface area of more than 10
      mm(2). The expression of putative progenitor cell markers p63alpha, ABCG2 and
      CK15, and the presence of MUC5AC- and periodic acid-Schiff-positive cells was
      compared with standard culture conditions (HCEC-3T3). RESULTS: Conjunctival
      epithelial cells cultured under HCEC-HCF and HCEC-3T3 conditions demonstrated
      strong immunoreactivity to p63alpha and ABCG2. Co-localization of CK15 and
      p63alpha revealed a subpopulation of CK15-positive cells under HCEC-3T3
      conditions compared with only a few CK15-positive cells found under HCEC-HCF
      conditions. MUC5AC- and periodic acid-Schiff-positive cells were much more common
      under HCEC-3T3 conditions than under HCEC-HCF conditions. These results were
      confirmed by reverse transcription-PCR. Cells in HCEC-HCF conditions demonstrated
      a significantly higher total colony-forming efficiency and a significantly higher
      percentage of colonies with holoclone-like morphology. CONCLUSIONS: The
      simulation of a niche environment in vitro by co-culturing mitotically active
      subconjunctival fibroblasts with conjunctival epithelial cells supports the
      maintenance of conjunctival cells with progenitor cell characteristics and
      therefore might be a useful tool to expand conjunctival epithelial progenitor
      cells in vitro for clinical use.

PMID- 21082889
TI  - An efficient method for generation of neural-like cells from adult human bone
      marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: Stem cell-based therapies to repair and replace lost neural cells are
      a highly promising treatment for CNS diseases. Bone marrow (BM)-derived
      mesenchymal stem cells (MSCs) have great potential as therapeutic agents against
      neurological maladies, since they have the ability to differentiate into neural
      phenotypes and can be readily isolated and expanded for autotransplantation with
      no risk of rejection. In our previous studies, we demonstrated that neural cells
      could be efficiently generated from mouse BM-derived MSCs by exposing cells to
      epigenetic modifiers and a neural environment. The main idea of this approach was
      the reactivation of pluripotency-associated genes in MSCs before exposing them to
      neural-inducing factors. AIM: In this study, we used a similar approach to
      efficiently generate neural cells from human BM-derived MSCs. METHOD: Neural
      induction was achieved by exposing cells simultaneously to inhibitors of DNA
      methylation and histone deacetylation, and pharmacological agents that increase
      cAMP levels. RESULTS: The expression of pluripotency and neural markers was
      confirmed with immunocytochemistry, western blot and real-time PCR. ELISA studies
      showed that these neurally induced-human MSCs cells released the neurotrophic
      factors glial cell-derived neurotrophic factor and brain-derived neurotrophic
      factor. CONCLUSION: Human MSCs that are neurally modified with this methodology
      could be a useful source of cells for CNS repair and regeneration.

PMID- 21082890
TI  - Graft and host interactions following transplantation of neural stem cells to
      organotypic striatal cultures.
AB  - AIMS: To investigate neural stem cell (NSC) interactions with striatal tissue
      following engraftment and the effects of growth factors. MATERIALS & METHODS:
      Organotypic striatal slice cultures established from neonatal rats were used as
      an ex vivo model system. Survival, integration and differentiation of grafted
      NSCs from the previously generated C17.2 clone and host tissue response were
      investigated weekly for 28 days in vitro. To direct grafted cells towards a
      neuronal lineage, the role of growth factor supplementation and serum-free
      culturing conditions was studied using neural stem cells overexpressing
      neurotrophin-3 and Neurobasal/B27 culture medium. RESULTS: Following engraftment,
      NSCs gradually integrated morphologically and formed a part of the host 3D
      cytoarchitecture. Compared with nongrafted cultures, NSC engraftment increased
      the overall survival of the organotypic cultures by 39%, and reduced the host
      cell necrosis by more than 80% (from 2.1 +/- 0.5% to 0.3 +/- 0.1%), the host cell
      apoptosis by more than 60% (from 1.4 +/- 0.4% to 0.5 +/- 0.1%) and the reactions
      to mechanical trauma by 30% (estimated by nestin and glial fibrillary acidic
      protein immunohistochemistry) 7 days after engraftment. Elevated neurotrophin-3
      production in NSCs and serum-free culturing conditions directed grafted NSCs
      towards a neuronal lineage as indicated by increased Tuj1 and Map2ab expression.
      However, this did not alter the survival of organotypic cultures. CONCLUSIONS:
      NSC engraftment was associated with rescue of imperiled host cells and reduction
      of host cell gliosis. These NSC effects were not related to the addition of
      growth factors, suggesting that other factors are involved in the supportive
      effects of the host following NSC engraftment.

PMID- 21082891
TI  - Skeletal myoblasts for cardiac repair.
AB  - Stem cells provide an alternative curative intervention for the infarcted heart
      by compensating for the cardiomyocyte loss subsequent to myocardial injury. The
      presence of resident stem and progenitor cell populations in the heart, and
      nuclear reprogramming of somatic cells with genetic induction of pluripotency
      markers are the emerging new developments in stem cell-based regenerative
      medicine. However, until safety and feasibility of these cells are established by
      extensive experimentation in in vitro and in vivo experimental models, skeletal
      muscle-derived myoblasts, and bone marrow cells remain the most well-studied
      donor cell types for myocardial regeneration and repair. This article provides a
      critical review of skeletal myoblasts as donor cells for transplantation in the
      light of published experimental and clinical data, and indepth discussion of the
      advantages and disadvantages of skeletal myoblast-based therapeutic intervention
      for augmentation of myocardial function in the infarcted heart. Furthermore,
      strategies to overcome the problems of arrhythmogenicity and failure of the
      transplanted skeletal myoblasts to integrate with the host cardiomyocytes are
      discussed.

PMID- 21082894
TI  - Mining the extracellular matrix for tissue engineering applications.
AB  - Tissue engineering is a rapidly evolving interdisciplinary field that aims to
      regenerate new tissue to replace damaged tissues or organs. The extracellular
      matrix (ECM) of animal tissues is a complex mixture of macromolecules that play
      an essential instructional role in the development of tissues and organs.
      Therefore, tissue engineering approaches rely on the need to present the correct
      cues to cells, to guide them to maintain tissue-specific functions. Recent
      research efforts have allowed us to mine various sequences and motifs, which play
      key roles in these guidance functions, from the ECM. Small conserved peptide
      sequences mined from ECM molecules can mimic some of the biological functions of
      their large parent molecules. In addition, these peptide sequences can be linked
      to various biomaterial scaffolds that can provide the cells with mechanical
      support to ensure appropriate cell growth and aid the formation of the correct
      tissue structure. The tissue engineering field will continue to benefit from the
      advent of these mined ECM sequences which have two major advantages over
      recombinant ECM molecules: material consistency and scalability.

PMID- 21082892
TI  - Mesenchymal stem cells for the treatment of neurodegenerative disease.
AB  - Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for
      cell therapy, and are currently being tested in US FDA-approved clinical trials
      for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus
      host disease and autoimmune disorders. They have been extensively tested and
      proven effective in preclinical studies for these and many other disorders. There
      is currently a great deal of interest in the use of MSCs to treat
      neurodegenerative diseases, in particular for those that are fatal and difficult
      to treat, such as Huntington's disease and amyotrophic lateral sclerosis.
      Proposed regenerative approaches to neurological diseases using MSCs include cell
      therapies in which cells are delivered via intracerebral or intrathecal
      injection. Upon transplantation into the brain, MSCs promote endogenous neuronal
      growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic
      connection from damaged neurons and regulate inflammation, primarily through
      paracrine actions. MSCs transplanted into the brain have been demonstrated to
      promote functional recovery by producing trophic factors that induce survival and
      regeneration of host neurons. Therapies will capitalize on the innate trophic
      support from MSCs or on augmented growth factor support, such as delivering brain
      derived neurotrophic factor or glial-derived neurotrophic factor into the brain
      to support injured neurons, using genetically engineered MSCs as the delivery
      vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain
      injury and stroke are currently ongoing. The current data in support of applying
      MSC-based cellular therapies to the treatment of neurodegenerative disorders are
      discussed.

PMID- 21082895
TI  - Regenerative medicine in Europe: global competition and innovation governance.
AB  - Leading European nations with strong biotech sectors, such as the UK and Germany,
      are investing heavily in regenerative medicine, seeking competitive advantage in
      this emerging sector. However, in the broader biopharmaceutical sector, the EU is
      outperformed by the USA on all metrics, reflecting longstanding problems: limited
      venture capital finance, a fragmented patent system, and relatively weak
      relations between academia and industry. The current global downturn has
      exacerbated these difficulties. The crisis comes at a time when the EU is
      reframing its approach to the governance of innovation and renewing its
      commitment to the goal of making Europe the leading player in the global
      knowledge economy. If the EU is to gain a competitive advantage in the
      regenerative medicine sector then it must coordinate a complex multilevel
      governance framework that encompasses the EU, member states and regional
      authorities. This article takes stock of Europe's current competitive position
      within the global bioeconomy, drawing on a variety of metrics in the three
      intersecting spheres of innovation governance: science, market and society. These
      data then provide a platform for reviewing the problems of innovation governance
      faced by the EU and the strategic choices that have to be confronted in the
      regenerative medicine sector.

PMID- 21082893
TI  - Myc transcription factors: key regulators behind establishment and maintenance of
      pluripotency.
AB  - The interplay between transcription factors, epigenetic modifiers, chromatin
      remodelers and miRNAs form the foundation of a complex regulatory network
      required for establishment and maintenance of the pluripotent state. Recent work
      indicates that Myc transcription factors are essential elements of this
      regulatory system. However, despite numerous studies, aspects of how Myc controls
      self-renewal and pluripotency remain obscure. This article reviews evidence
      supporting the placement of Myc as a central regulator of the pluripotent state
      and discusses possible mechanisms of action.

PMID- 21082897
TI  - Missed cancerous lesions in emergency laparoscopic surgery: retrospective study
      of 2074 cases.
AB  - Abdominal laparoscopy is a widely accepted surgical procedure effective even for
      acute abdominal ailments. However, one major concern in using abdominal
      laparoscopy is missed lesions, in the past this has not been adequately explored.
      The aim of this retrospective study, therefore, is to evaluate cancerous lesions
      that are missed during emergency laparoscopic surgeries. The medical records of
      2074 patients who had a laparoscopy from March 1996 to April 2006 for acute
      abdomen symptoms, including diagnostic laparoscopy (n = 119), laparoscopic
      appendectomy (n = 1336), laparoscopic duodenorrhaphy (n = 30), and laparoscopic
      cholecystectomy (n = 589) were reviewed. Missed cancerous lesions included cecal
      cancer (n = 2), sigmoid cancer (n = 1), and jejunum lymphoma (n = 1). The
      incidence of missed cancerous lesions in an emergency laparoscopic surgery is
      0.19%, mainly due to its lower tactile sensitivity compared to the direct hand
      palpation and masqueraded by inflammatory process. Therefore, careful observation
      is recommended for post-emergency laparoscopic patients and follow-up should be
      performed within three months, especially for patients with intra-abdominal
      and/or severe inflammation status.

PMID- 21082898
TI  - An easy new approach to the laparoscopic treatment of large adnexal cysts.
AB  - We describe a technique for laparoscopically assisted extracorporeal cystectomy
      or adnexectomy of large adnexal cysts without spillage of the cyst contents. At
      open laparoscopy, a suction tube decompressed the adnexal cyst from the 2-cm
      umbilical incision and the puncture hole was closed by the purse string tie,
      which was followed by extra-corporeal excision of the cyst. With this method, we
      prevent cyst spillage in three ways. Firstly, the cyst is aspirated
      extracorporeally. Secondly, when the cyst is totally collapsed, the puncture
      point is closed with a 1-o Vicryl purse suture and pulled to the umbilicus.
      Thirdly, as soon as a part of the mass is delivered from the abdomen, it is lined
      with moist gauze. This method provides excellent visualization and control of the
      penetration site during aspiration, and minimizes the chances of the cyst
      contents leaking into the peritoneal cavity. This method was successfully used
      with 12 patients, including four cystadenomas, one serous cystadenoma, three
      dermoid cysts (with one pregnant woman who successfully spontaneously delivered a
      normal baby at term), two low malignant potential ovarian tumors and one grade I
      endometrioid adenocarcinoma. The cancer patient has shown no recurrence after a
      follow-up of three years.

PMID- 21082899
TI  - Removal of an encrustation catheter impacted in the prostatic urethra by holmium
      laser.
AB  - It is difficult to withdraw an encrusted urinary catheter, especially when it is
      impacted in the prostatic urethra. This article reports our experience with
      removing an encrusted urethral catheter using holmium laser through the
      suprapubic cystostomy tract.

PMID- 21082900
TI  - Transvaginal aspiration of ovarian cysts: our experience over 121 cases.
AB  - We performed an evaluation of ultrasound-guided transvaginal aspiration of
      ovarian cysts as a viable alternative to surgery in 104 reproductive and 17
      postmenopausal women. One-hundred and twenty-one patients with a simple >4 cm
      diameter ovarian cyst, with a benign appearance on ultrasound as well as on
      clinical and blood examination, underwent transvaginal fine needle aspiration of
      the cyst under ultrasonographic control. One-hundred and four patients were of
      reproductive age and 12 were postmenopausal. Sixty women who were of reproductive
      age and in which OCP treatment was not contraindicated followed a six-month
      therapy with oral contraceptives after the intervention. In the group of patients
      of reproductive age under OCP treatment the cyst persisted in nine of the 60
      women (recurrence rate 15%). In the other group of patients of reproductive
      age,under no OCP treatment, the recurrence rate was 47% (21 of the 44 women). In
      the group of postmenopausal patients, the cyst persisted in ten out of 17 cases
      (recurrence rate 58,9%). Transvaginal aspiration of ovarian cysts is a reliable
      alternative to surgery with many advantages such as excellent tolerance, low risk
      and cost of complications and recurrence. The OCP treatment after aspiration
      seems to increase the success rate of expectant management.

PMID- 21082902
TI  - Laparoscopic radiofrequency ablation of liver tumors: comparison of MR guidance
      versus conventional laparoscopic ultrasound for needle positioning in a phantom
      model.
AB  - Laparoscopic radiofrequency ablation (LapRFA) is an established procedure for
      liver tumors in patients who are unsuitable for resection. A novel technique of
      magnetic resonance (MR) guided needle positioning during LapRFA was developed and
      compared to conventional ultrasound (US) guidance in a phantom model. MR-guided
      procedures were conducted in a 1.0 tesla high field open MR using an MR
      compatible endoscope and camera. The ultrasound-guided procedure was performed
      with a clinically established laparoscopy setup and a 2D laparoscopic US probe.
      During both techniques an identical monopolar non-ferromagnetic RFA needle and a
      silicon-based phantom model were applied. Finally needle positioning was
      performed by two surgeons and one interventionalist. Time to needle placement and
      number of trials were recorded and statistically analyzed. MR-guided needle
      positioning under laparoscopic control was technically feasible. Average time to
      correct needle placement was 2' 6" in the LapUS group and 1' 54" in the MR group.
      The number of trials was 3.2 in the LapUS group and 2.6 in the MR group. Image
      quality was assessed by all participants. MR images showed a better tissue to
      tumor contrast and allowed an improved orientation due to multiplanar
      visualization. MR-guided laparoscopic RFA is a promising technique offering
      multiplanar needle positioning with high soft tissue contrast with immediate
      therapy control. In a phantom model it showed comparable results regarding needle
      positioning to the established technique of laparoscopic US guidance.

PMID- 21082901
TI  - Evaluating tumors in transcatheter arterial chemoembolization (TACE) using dual
      phase cone-beam CT.
AB  - C-arm cone-beam computed tomography (CBCT) can be used to visualize tumor-feeding
      vessels and parenchymal staining during transcatheter arterial chemoembolization
      (TACE). To capture these two phases, all current commercially available CBCT
      systems necessitate two separate contrast-enhanced scans. In this feasibility
      study, we report initial results of novel software that enhanced our current CBCT
      system to capture these two phases using only one contrast injection. Novelty of
      this work is the addition of software that enabled the acquisition of two
      sequential, back-to-back CBCT scans (dual-phase CBCT, DPCBCT) so both tumor
      feeding vessels and parenchyma are captured using only one contrast injection. To
      illustrate our initial experience, DPCBCT was used for TACE treatments involving
      lipiodol, drug-eluting beads, and Yttrium-90 radioembolizing microspheres. For
      each case, the DPCBCT images were compared to pre-intervention contrast-enhanced
      MR/CT. DPCBCT is feasible for TACE treatments and the preliminary results show
      positive correlation with pre-intervention conventional CT and MR. In addition,
      the degree of embolization can be monitored. DPCBCT is a promising technology
      that provides comprehensive visualization of tumor-feeding vessels and
      parenchymal staining using a single injection of contrast. DPCBCT could
      potentially be used during TACE to verify catheter position and monitor the
      embolization effect.

PMID- 21082903
TI  - Comparison of the ultrasonic scalpel to CO(2) laser in cervical conization.
AB  - The aim of the present study was to compare the efficacy of CO(2) laser with that
      of ultrasonic scalpel in cervical conization in terms of intraoperative and
      postoperative outcome. One-hundred and two patients were submitted to cervical
      conization by ultrasonically activated scalpel, while 97 patients were submitted
      to cervical conization by use of CO(2) laser. Comparison of mean estimated blood
      loss, mean operative time and mean cone volume between the two groups was
      performed with Student t test. Postoperative complications were compared by x(2)
      test. There was no statistical significance regarding the mean operating time,
      mean blood loss, mean cone volume and postoperative complications in the two
      methods. However, thermal artifacts at the cone margins were minimal in the
      harmonic group (2/102 cones, 1.96%), while in the laser group they were
      considerably more (18/97 cones, 18.5%) (p < 0.05). Conization using the harmonic
      scalpel is as safe and effective as the CO(2) laser procedure. It is cheaper,
      produces less smoke, better visual field and less thermal artifacts in the cone
      margins. It is a reliable method that overcomes most problems associated with the
      CO(2) laser, as well as the other conventional conization procedures.

PMID- 21082904
TI  - Indicating shortcomings in surgical lighting systems.
AB  - Ergonomic problems of surgical lighting systems have been indicated by surgeons;
      however, the underlying causes are not clear. The aim of this study is to assess
      the problems in detail. Luminaire use during 46 hours of surgery was observed and
      quantified. Furthermore, a questionnaire on perceived illumination of and
      usability problems with surgical luminaires was issued among OR-staff in 13
      hospitals. The results showed that every 7.5 minutes a luminaire action (LA)
      takes place, intended to reposition the luminaire. Of these LAs, 74% were
      performed by surgeons and residents. For 64% of these LAs the surgical tasks of
      the OR-staff were interrupted. The amount of LAs to obtain a well-lit wound, the
      illumination level, shadows, and the illumination of deep wounds were most
      frequently indicated lighting aspects needing improvement. Different kinematic
      aspects of the pendant system of the lights that influence usability were also
      mentioned: High forces for repositioning, ease of focusing and aiming, ease of
      moving, collisions of the luminaire, entangling of pendant arms, and
      maneuverability. Based on these results conclusions regarding the improvement of
      surgical lighting systems are formulated. Focus for improvements should be on
      minimizing the need for repositioning the luminaire, and on minimizing the effort
      for repositioning.

PMID- 21082905
TI  - Clinical success of ERCP procedures in nonagenarian patients with bile duct
      stones.
AB  - In the general population, endoscopic retrograde cholangiopancreatography (ERCP)
      procedures are the gold standard in the treatment of bile duct stones. However,
      repeat endoscopic procedures and sometimes even open surgery are needed in
      difficult cases with retaining bile duct stones. The aim of the present study was
      to determine the clinical success of ERCP procedures in the treatment of bile
      duct stones in extremely old patients. A retrospective data review comprising
      prospective data collection and double-entry bookkeeping of 23 therapeutic ERCPs
      in 20 nonagenarians with bile duct stones was conducted between 1997 and 2007.
      The primary ERCP procedure was the definitive treatment in 17 out of 20 patients
      with bile duct stones, giving a clinical success rate of 85 % for the first
      endoscopic procedure. In the remaining three patients, a repeat ERCP procedure
      had to be done in the follow-up. After these three repeat procedures with
      successful outcome, the clinical success of endoscopic treatment was 100%. There
      was no further recurrent biliary obstruction in any of the patients prior to
      death which occurred after a mean of 38 months (two patients are still alive),
      and no open surgery had to be performed in these patients. To be concluded,
      endoscopic treatment modality seems to be excellent in extremely elderly patients
      with bile duct stones.

PMID- 21082906
TI  - Interview with Anne Kandler, winner of the 2009 Gabriel W. Lasker Prize by Franz
      Manni.

PMID- 21082907
TI  - Ancient local evolution of African mtDNA haplogroups in Tunisian Berber
      populations.
AB  - Our objective is to highlight the age of sub-Saharan gene flows in North Africa
      and particularly in Tunisia. Therefore we analyzed in a broad phylogeographic
      context sub-Saharan mtDNA haplogroups of Tunisian Berber populations considered
      representative of ancient settlement. More than 2,000 sequences were collected
      from the literature, and networks were constructed. The results show that the
      most ancient haplogroup is L3*, which would have been introduced to North Africa
      from eastern sub-Saharan populations around 20,000 years ago. Our results also
      point to a less ancient western sub-Saharan gene flow to Tunisia, including
      haplogroups L2a and L3b. This conclusion points to an ancient African gene flow
      to Tunisia before 20,000 BP. These findings parallel the more recent findings of
      both archaeology and linguistics on the prehistory of Africa. The present work
      suggests that sub-Saharan contributions to North Africa have experienced several
      complex population processes after the occupation of the region by anatomically
      modern humans. Our results reveal that Berber speakers have a foundational
      biogeographic root in Africa and that deep African lineages have continued to
      evolve in supra-Saharan Africa.

PMID- 21082908
TI  - Biocultural emergence of the Amazigh (Berbers) in Africa: comment on Frigi et al.
      (2010).

PMID- 21082909
TI  - Association of D16S515 microsatellite with specific language impairment on
      Robinson Crusoe Island, an isolated Chilean population: a possible key to
      understanding language development.
AB  - Specific language impairment (SLI) is a developmental language disorder that
      occurs for no known reason. The disorder affects 2-8% of children. Some
      scientific evidence suggests that genetic factors are implicated in the etiology
      of SLI. The disorder is genetically complex. Two novel loci, SLI1 on chromosome
      16q24 (MIM 606711) and SLI2 on chromosome 19q13 (MIM 606712), have been found to
      be highly correlated with SLI. Four genes have been identified as susceptibility
      genes. SLI occurs at an unusually elevated incidence (35%) among the population
      of Robinson Crusoe Island (Chile), which also has a high consanguinity rate. This
      finding supports the influence of genetic mechanisms in the transmission of SLI
      based on a founder effect. To investigate further the genetic involvement in this
      population, we collected blood samples from 115 islanders from 13 families with a
      language-impaired proband and from 18 families with a normal-language proband.
      The analysis of micro satellite marker D16S515, located in locus SLI1,
      demonstrated that the 230-bp allele was correlated with SLI and that the 232-bp
      allele was correlated with normal language development. The domain containing the
      D16S515 marker, therefore, may play a role in language development.

PMID- 21082910
TI  - Genetic characterization of indigenous peoples from Oaxaca, Mexico, and its
      relation to linguistic and geographic isolation.
AB  - We used 15 short tandem repeat (STR) loci (D8S1179, D21S11, D7S820, CSF1PO,
      D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, and
      FGA) to genetically characterize 361 individuals from 11 indigenous populations
      (Amuzgo, Chinanteco, Chontal, Huave, Mazateco, Mixe, Mixteco, Triqui, Zapoteco
      del Istmo, Zapoteco del Valle, and Zoque) from Oaxaca, Mexico. We also used
      previously published data from other Mexican peoples (Maya, Chol, Tepehua, Otomi,
      and Mestizos from northern and central Mexico) to delineate genetic relations,
      for a total of 541 individuals. Average heterozygosity (H) was lower in most
      populations from Oaxaca (range 0.687 in Zoque to 0.756 in Chontal) than values
      observed in Mestizo populations from Mexico (0.758 and 0.793 in central and
      northern Mestizo, respectively) but higher than values observed in other
      Amerindian populations from South America; the same relation was true for the
      number of alleles (n(a) ). We tested (using the software Structure) whether major
      geographic or linguistic barriers to gene flow existed among the populations of
      Oaxaca and found that the populations appeared to constitute one or two genetic
      groups, suggesting that neither geographic location nor linguistics had an effect
      on the genetic structure of these culturally and linguistically highly diverse
      indigenous peoples. Moreover, we found a low but statistically significant
      between-population differentiation. In addition, the genetic structure of Oaxacan
      populations did not fit an isolation-by-distance model. Finally, using AMOVA and
      a Bayesian clustering approach, we did not detect significant geographic or
      linguistic barriers to gene flow within Oaxaca. These results suggest that the
      indigenous communities of Oaxaca, although culturally isolated, can be
      genetically defined as a large, nearly panmictic population in which migration
      could be a more important population mechanism than genetic drift. Finally,
      compared with outgroups in Mexico (both indigenous peoples and Mestizos), three
      groups were apparent. Among them, only the Otomi population from Hidalgo has a
      different culture and language.

PMID- 21082911
TI  - Genetic analysis of six communities of Mbya-Guarani inhabiting northeastern
      Argentina by means of nuclear and mitochondrial polymorphic markers.
AB  - Autosomal STRs, Y-chromosome markers, and mitochondrial DNA sequences were
      investigated in six Mbya-Guarani villages (Fortin M'Borore, Yryapu, Tabay, Kaaguy
      Poty, Jejy, and Yaboti), all of them settled within the province of Misiones,
      northeastern Argentina. One hundred twenty-one unrelated individuals were
      analyzed. The study involved typing fifteen autosomal STRs, nine Y-chromosome
      STRs, and four biallele loci in the nonrecombinant region of the Y chromosome,
      sequencing the mtDNA of hypervariable regions I and II, and detecting the 9-bp
      ins/del in region V of mtDNA. All autosomal STRs were in Hardy-Weinberg
      equilibrium. The four major native American mtDNA haplogroups were represented in
      the sample. Haplogroups A2 and D1 exhibited the highest frequencies (40.5% and
      36.0%, respectively), and haplogroups B2 and C1 appeared to be less frequent
      (17.5% and 6.0%, respectively). The native American haplogroup Q1a3a was observed
      in a relevant proportion (88.8%). In addition, a nine-STR Y-chromosome haplo-type
      (DYS19*13, DYS389I*14, DYS389II*31, DYS390*24, DYS391*11, DYS392*14, DYS393*11,
      DYS385A*14, DYS385B*16) exhibited a frequency of more than 36%. Our results
      indicate that the analyzed Argentinean Guarani individuals are genetically more
      closely related to Guarani from Brazil [genetic distance (Deltau)(2) = 0.48] than
      to other related tribes that are geographically closer. Statistical approaches
      based on autosomal data do not support the hypothesis of genetic drift previously
      proposed; however, this apparent discrepancy might be due to the lack of
      sensitivity of the autosomal markers used here.

PMID- 21082912
TI  - Autochthony and HLA frequencies in the Netherlands: when surnames are useless
      markers.
AB  - To study the genetic variability of the HLA loci A, B, DR, and DQ in the
      Netherlands, we analyzed more than 13,000 typings provided by the Dutch National
      Reference Laboratory for Histocompatibility. To investigate any possibly existing
      population structure, we subdivided the typings by the geographic location of
      residency of donors and by the historical belonging of their surnames to given
      provinces. Concerning possible geographic patterns, we found no significant
      differences between the four provinces examined (North Holland, South Holland,
      Utrecht, Zeeland). To assess whether such a negative result was related to recent
      immigration to the area (the richest of the country) that erased possible
      preexisting patterns of HLA diversity, we reprocessed the database according to
      the surnames of HLA donors. We obtained two groups: (1) those having a surname
      typical of the four provinces they inhabit and (2) those with surnames coming
      from elsewhere. Such an analysis was made possible because of the availability of
      a database concerning the geographic origin of most Dutch surnames. Even with
      this surname-based approach, no major differences were found. We conclude that
      either the western part of the Netherlands was genetically homogeneous before the
      official introduction of Dutch surnames two centuries ago by Napoleon or surnames
      have no power in dissecting HLA variability; that is, such variability is the
      result of recombination phenomena that surnames cannot mirror because they are
      transmitted virtually unchanged generation after generation. A comparable study
      by other investigators recommended the use of family names to identify rare HLA
      haplotypes in France, but now, concerning the Netherlands, we find opposite
      results. We suggest that a few typing centers may be sufficient to type bone
      marrow donors, because HLA genetic differences between the different provinces of
      the Netherlands are extremely low. To maximize the number of donors, such centers
      should be located in areas providing the easiest access to the largest population
      of possible donors, thus disregarding the search for a local variability that we
      did not find.

PMID- 21082913
TI  - Response to Cavalli-Sforza interview [Human Biology 82(3):245-266 (June 2010)].

PMID- 21082917
TI  - Anticoagulants from hematophagous animals.

PMID- 21082919
TI  - Eltrombopag for the treatment of idiopathic thrombocytopenic purpura.
AB  - Strategies aimed at stimulating platelet production are a rational approach to
      the treatment of patients with primary immune thrombocytopenia, as, for many of
      them, the low platelet count is a consequence of ineffective megakaryopoiesis.
      Recently, intense clinical trial activity in immune thrombocytopenia has been
      reported for second-generation thrombopoietic agents. These novel molecules bear
      no structural resemblance to thrombopoietin, but still bind and activate the
      thrombopoietin receptor. One of these agents is eltrombopag (formerly SB497115),
      an orally available, small organic compound. Randomized trials have shown the
      short-term efficacy of eltrombopag in elevating the platelet count of most adult
      patients with immune thrombocytopenia unresponsive to at least one standard
      treatment. No significant adverse events were observed, but long-term safety data
      are still lacking. Ongoing studies will reveal the potential of this agent in the
      management of immune thrombocytopenia for long-term maintenance therapy, as well
      as its relative benefit compared with standard-of-care treatment.

PMID- 21082920
TI  - FLT3 inhibitors in acute myeloid leukemia.
AB  - The fms-like tyrosine kinase 3 (FLT3) plays an important role in both normal and
      malignant hematopoiesis. Activating mutations in the FLT3 receptor can be
      detected in approximately 30% of acute myeloid leukemias (AMLs) and are
      associated with a distinctly poor clinical outcome for patients. There are now
      several classes of FLT3 inhibitors in development with varying degrees of potency
      and selectivity for the target, including several in late-phase clinical trials
      in combination with chemotherapy. Major clinical responses in AML patients
      receiving single-agent FLT3 inhibitors have been rare, although transient
      peripheral blood blast reduction is common. Given such biological suggestion and
      preclinical activity, FLT3 inhibitors hold promise in improving the outcome of
      patients with mutant FLT3 AML. This review summarizes the current attempts to
      target this molecule, with emphasis on the validity of the target, the results of
      the clinical trials evaluating the FLT3 inhibitors in AML, the optimal use of
      these compounds and the mechanisms of resistance.

PMID- 21082922
TI  - Managing cancer-related venous thromboembolic disease: low-molecular-weight
      heparins and beyond.
AB  - Venous thromboembolism is a major contributor to the morbidity and mortality of
      patients with cancer. For patients undergoing cancer surgery, several trials
      support the safety and efficacy of unfractionated heparin and of low-molecular
      weight heparin for the prevention of venous thromboembolism, while data regarding
      the efficacy and safety of these agents in the setting of medical hospitalization
      is less definitive and must be extracted from trials including noncancer patients
      with different thrombotic risk factors. Randomized clinical studies confirm that
      patients with cancer who develop venous thromboembolism have superior outcomes
      when treated with long-term low-molecular-weight heparin as compared with
      warfarin. Novel anticoagulants that are orally bioavailable and function by
      directly inhibiting factor Xa or thrombin are entering the market. To date, data
      regarding the efficacy and safety of these novel anticoagulants as venous
      thromboembolism prophylaxis and treatment in cancer patients are not available
      and must be extracted from larger trials with heterogeneous patient populations.

PMID- 21082921
TI  - Role of epigenetic therapy in myelodysplastic syndrome.
AB  - Myelodysplastic syndrome, characterized by ineffective hematopoiesis and
      cytopenias, remains a lethal disease. Until recently, patients with
      myelodysplastic syndrome have been managed supportively with blood product
      transfusions and growth factors, until they succumb to infections, bleeding
      complications or transformation to acute leukemia. The discovery that epigenetic
      factors play an important role in cancer, and specifically in myelodysplastic
      syndrome, has led to the recent approval of several new therapies that will make
      a significant impact on this disease. Epigenetics refers to a number of
      biochemical modifications to chromatin that do not alter the primary DNA
      sequence, but play an important role in genomic regulation at the level of gene
      transcription. Epigenetic factors can be passed on from a cell to its progeny and
      can mimic traditional genetic lesions that are implicated in cancer. Unlike
      genetic abnormalities, however, epigenetic changes, such as DNA methylation or
      histone deacetylation, can be manipulated pharmacologically. Recently developed
      hypomethylating agents and histone deacetylase inhibitors have shown significant
      biological and clinical activity in myelodysplastic syndrome. These drugs have
      been well-tolerated by patients and have been shown to alter the course of this
      disease. In order to use these drugs optimally, however, we need to better
      understand the role of these epigenetic changes: how they contribute to the
      disease process, how we can use them to better select patients and how we can use
      combinations to target them more effectively.

PMID- 21082923
TI  - Diagnosis of antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is a multisystem autoimmune disease, characterized by
      recurrent vascular thrombosis and/or pregnancy losses in the presence of
      persistently positive antiphospholipid antibodies. In clinical practice, testing
      for anticardiolipin antibodies and lupus anticoagulant is mandatory for the
      laboratory diagnosis of antiphospholipid syndrome. Identification of patients
      with antiphospholipid syndrome is important, as prophylactic anticoagulant
      therapy may prevent thrombosis from recurring, and treatment during pregnancy can
      improve fetal and maternal outcome.

PMID- 21082924
TI  - Autoimmune hemolytic anemia: classification and therapeutic approaches.
AB  - Autoimmune hemolytic anemia (AIHA) is a relatively uncommon cause of anemia.
      Classifications of AIHA include warm AIHA, cold AIHA (including mainly chronic
      cold agglutinin disease and paroxysmal cold hemoglobinuria), mixed-type AIHA and
      drug-induced AIHA. AIHA may also be further subdivided on the basis of etiology.
      Management of AIHA is based mainly on empirical data and on small, retrospective,
      uncontrolled studies. The therapeutic options for treating AIHA are increasing
      with monoclonal antibodies and, potentially, complement inhibitory drugs. Based
      on data available in the literature and our experience, we propose algorithms for
      the treatment of warm AIHA and cold agglutinin disease in adults. Therapeutic
      trials are needed in order to better stratify treatment, taking into account the
      promising efficacy of rituximab.

PMID- 21082925
TI  - Clinical penetrance of C282Y homozygous HFE hemochromatosis.
AB  - Following the discovery of the HFE gene, it became apparent that C282Y homozygous
      HFE hemochromatosis is the most common autosomal recessive genetic disorder in
      populations of northern European descent, where it attains a maximum prevalence
      of approximately 1 in 200. Cross-sectional studies have revealed that the
      clinical penetrance of symptoms of iron-loading disease is relatively low and
      highly variable. Although there is no standard definition of clinical penetrance,
      large studies of newly diagnosed C282Y homozygotes that have specifically
      assessed liver disease have obtained data showing that penetrance occurs in
      between 24 and 43% of males and 1 and 14% of females. This relatively low
      clinical penetrance is largely unexplained. Current evidence suggests a limited
      role for digenic inheritance of mutations in iron homeostasis genes in modifying
      the penetrance of HFE hemochromatosis. Currently, the single most important
      environmental and genetic variables promoting penetrance are alcohol consumption
      and male gender, respectively. With genetic analyses becoming simpler to perform,
      new genetic modifiers of hepatic iron loading and liver fibrogenesis await
      identification.

PMID- 21082926
TI  - Pathophysiologic mechanisms, clinical features and treatment of idiopathic
      neutropenia.
AB  - The term idiopathic neutropenia describes a benign disorder of granulopoiesis
      characterized by the unexplained reduction in the absolute neutrophil count below
      the lower limit of the normal range for a prolonged period. Recent studies have
      provided evidence that this neutropenic condition comprises two distinct disease
      entities on the basis of the underlying pathogenetic mechanisms: first, the
      primary autoimmune neutropenia mediated by autoantibodies against mature
      neutrophils and/or their bone marrow progenitor/precursor cells; and second, the
      previously named chronic idiopathic neutropenia, that might now be called chronic
      immunologic neutropenia, characterized by T-cell- and cytokine-mediated
      suppression of granulopoiesis. Despite the differences in the bone marrow
      granulocytic progenitor cell reserves that actually reflect the differences in
      the implicated pathophysiologic mechanisms, both disease entities usually display
      an uncomplicated clinical course with minimal symptoms. Treatment decisions
      should be individualized on the basis of patients' clinical course and the
      indicated therapies are analyzed in this review. The clinical and laboratory data
      characterizing these neutropenic conditions and the available in vitro data that
      have led to remarkable progress in the understanding of the pathophysiology of
      both disorders are also summarized.

PMID- 21082928
TI  - Minimal residual disease in acute myeloid leukemia: already predicting a safe
      haven?

PMID- 21082929
TI  - Platelet transfusions in neonates: questions and answers.

PMID- 21082931
TI  - Clofarabine in leukemia.
AB  - Clofarabine is a second-generation purine nucleoside analogue that has been
      synthesized to overcome the limitations and incorporate the best qualities of
      fludarabine and cladribine. Clofarabine acts by inhibiting ribonucleotide
      reductase and DNA polymerase, thereby depleting the amount of intracellular
      deoxynucleoside triphosphates available for DNA replication. Compared with its
      precursors, clofarabine has an increased resistance to deamination and
      phosphorolysis, hence better stability, as well as higher affinity to
      deoxycytidine kinase (dCyd), the rate-limiting step in nucleoside
      phosphorylation. In 1993, the first Phase I study was initiated in patients with
      hematologic and solid malignancies. Since then, clofarabine has demonstrated
      single-agent antitumor activity in pediatric and adult acute leukemia. Owing to
      its unique properties of biochemical modulation when used in combination with
      other established antileukemic drugs, mainly cytarabine, combination regimens
      containing clofarabine are being evaluated. A review of the English literature
      was performed that included original articles and related reviews from the
      MEDLINE (PubMed) database and from abstracts based on the publication of meeting
      materials. This article describes the development, pharmacology and clinical
      activity of clofarabine, as well as its emerging role in the treatment of acute
      leukemia, myelodysplastic syndrome and solid tumors.

PMID- 21082932
TI  - Post-transplant lymphoproliferative disorders following solid-organ
      transplantation.
AB  - A post-transplant lymphoproliferative disorder (PTLD) is an uncommon but serious
      complication following solid-organ transplantation. The incidence varies,
      depending on the type of organ transplanted, the degree of immunosuppression, the
      number of episodes of acute rejection and a patient's immune status to Epstein
      Barr virus. The incidence of PTLD is thought to be bimodal; cases in the first
      year after solid-organ transplantation are typically related to Epstein-Barr
      virus. A second incidence occurs more than 1 year following transplantation and
      is typically not related to Epstein-Barr virus. A variety of therapeutic
      approaches has been used for these patients, with more recent strategies
      including the use of rituximab, with or without combination chemotherapy. Efforts
      continue to be made to improve the outcome of patients with PTLD.

PMID- 21082933
TI  - Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia as a model of
      rational drug design in cancer.
AB  - Many biological and clinical features of chronic myeloid leukemia make it as a
      paradigm of rational drug design in human cancer. Chronic myeloid leukemia was
      the first malignancy to be linked to a clear genetic anomaly, the Philadelphia
      chromosome and, at present, it is probably the best understood of all human
      malignancies. Studies of the disease pathology revealed that the molecular
      consequence of the Philadelphia translocation is a BCR-ABL chimeric gene, which
      encodes a constitutively active tyrosine kinase with wholesale range of
      biological activities. Animal models have validated the direct role of the BCR
      ABL protein in malignant transformation and subsequent research confirmed that
      its enhanced tyrosine kinase activity is essential and sufficient for the
      leukemogenesis. The very existence of a single genetic abnormality, presented in
      essentially all patients with the disease, made it an effective target for
      molecularly designed therapeutic approaches for the disease. The advent of
      tyrosine kinase inhibitors, designed specifically to inhibit the tyrosine kinase
      activity of the BCR-ABL oncoprotein, represents one of the major innovations in
      cancer therapy and may serve as a model for, how discoveries of disease
      pathogenesis may be translated into the development of successful targeted
      therapies in cancer medicine.

PMID- 21082934
TI  - Mucositis in malignant hematology.
AB  - Mucosal barrier injury (MBI), also known as mucositis, is the result of the
      cytotoxic effects of many treatments given for hematological malignancies (HMs)
      and represents a major source of potentially devastating clinical complications
      and negative consequences afflicting the patient's management, such as a longer
      hospitalization, the need of analgesic and total parenteral nutrition use, and
      increased costs. The available measures for the prevention and treatment of MBI
      have been substantially limited to the control of pain, infection, bleeding and
      nutrition. However, in the last decade, a better insight into the complex
      pathogenesis of MBI has led to the development of novel therapeutic options, such
      as palifermin, which has been one of the major breakthroughs in the management of
      this condition, potentially allowing a targeted approach to MBI. Nevertheless,
      and despite these significant advances, MBI still remains a significant clinical
      problem in the management of HM and an important burden of sufferance for
      afflicted patients.

PMID- 21082935
TI  - HLA-G expression in hematologic malignancies.
AB  - HLA-G is a nonclassic MHC class I molecule that functions as an immunomodulatory
      molecule;which has a direct inhibitory effect on immune responses and induces the
      generation of suppressor or regulatory cells. The relevance of HLA-G in various
      pathologic conditions, such as transplantation, autoimmunity and infectious and
      malignant diseases, has been extensively investigated. In the context of
      hematologic malignancies, such as acute myeloid leukemia, chronic lymphocytic
      leukemia and lymphoma, the expression and clinical significance of HLA-G was
      discussed; however, interpretation remains controversial. In this review, we
      summarize HLA-G expression in hematologic malignancies and emphasize the clinical
      relevance of this expression to disease progression. The possible mechanism
      involved in HLA-G expression regulation is also highlighted.

PMID- 21082936
TI  - HIF pathway mutations and erythrocytosis.
AB  - Erythrocytosis is present when there is an increase in the red cell mass, usually
      accompanied by an elevated hemoglobin and hematocrit. This occurs when there is
      an intrinsic defect in the erythroid component of the bone marrow or for
      secondary reasons when an increase in erythropoietin production drives red cell
      production. In normoxic conditions, HIF-alpha interacts with the other proteins
      in the HIF pathway and is destroyed, but in hypoxic conditions, HIF-alpha binds
      to HIF-beta and alters the expression of downstream genes, including the
      erythropoietin gene. The end result is an increase in erythropoietin production.
      Mutations in any of the genes in the HIF pathway could lead to changed proteins,
      abnormalities in the degradation of HIF-alpha and, ultimately, result in
      increased erythropoietin levels. A number of mutations in the VHL, PHD2, and
      HIF2A genes have been identified in individuals. These mutations lead to
      erythrocytosis. The clinical results of these mutations may include some major
      thromboembolic events in young patients.

PMID- 21082939
TI  - How do PIG-A mutant paroxysmal nocturnal hemoglobinuria stem cells achieve clonal
      dominance?

PMID- 21082937
TI  - Global burden, distribution and prevention of beta-thalassemias and hemoglobin E
      disorders.
AB  - The beta-thalassemias, including the hemoglobin E disorders, are not only common
      in the Mediterranean region, South-East Asia, the Indian subcontinent and the
      Middle East but have now become a global problem, spreading to much of Europe,
      the Americas and Australia owing to migration of people from these regions.
      Approximately 1.5% of the global population are heterozygotes or carriers of the
      beta-thalassemias. While the overall frequencies of carriers of these disorders
      are known in most countries, there have been few attempts at micromapping and
      wherever this has been done, significant variations are seen even within small
      geographic regions. Thus, the figures for the estimated numbers of births each
      year of homozygous beta-thalassemia and the severe compound states involving
      other hemoglobin disorders may be an underestimate. Screening strategies have
      varied from premarital to antenatal in different countries depending on socio
      cultural and religious customs in different populations. Prenatal diagnosis
      programs are ongoing in many countries and the knowledge of the distribution of
      mutations has facilitated the establishment of successful control programs. Many
      of these were through North-South partnerships and networking. Yet, there are
      many countries in Asia where they are lacking, and South-South partnerships are
      now being developed in South-East Asia and the Indian subcontinent to link
      centers with expertise to centers where expertise needs to be developed. Although
      the carrier frequencies will remain unaltered, this will eventually help to bring
      down the burden of the birth of affected children with beta-thalassemias and
      hemoglobin E disorders in Asia.

PMID- 21082940
TI  - Management of bleeding in patients on antithrombotics: maintaining the balance
      between thrombosis and hemorrhage.

PMID- 21082942
TI  - Use of defibrotide in the treatment and prevention of veno-occlusive disease.
AB  - Hepatic veno-occlusive disease (VOD) is one of the most important complications
      of high-dose chemotherapy and stem cell transplantation. VOD is a clinical
      syndrome characterized by jaundice, hepatic enlargement and fluid retention
      typically seen by day +30 after transplantation. Severe VOD is complicated by
      multiorgan failure and a high mortality rate approaching 100%. Defibrotide (DF)
      is a novel agent with both antithrombotic and fibrinolytic properties that has
      emerged as an effective therapy for severe VOD. In Phase II studies, treatment of
      severe VOD has resulted in complete responses of 30-60% and survival past day 100
      ranging between 32-50%. A Phase III, historically controlled study of DF for
      treatment of severe VOD has recently been completed and results are awaited with
      interest. In addition, DF may be effective prophylaxis for VOD in high-risk
      patients. This review will focus on a summary of the pharmacology of DF and the
      clinical evidence for its use in VOD.

PMID- 21082943
TI  - HematideTM for the treatment of chronic kidney disease-related anemia.
AB  - HematideTM is an investigational erythropoiesis-stimulating agent (ESA) being
      evaluated for the treatment of anemia in chronic kidney disease patients. It is a
      dimeric peptide conjugated to a polymeric polyethylene glycol moiety with a
      sequence completely unrelated to erythropoietin (EPO). Despite this, it is
      capable of binding to the EPO receptor and promote erythropoiesis through the
      pathway common to EPO and other ESAs. The drug is partially cleared by the
      kidney; consequently, its half-life is much longer in the presence of renal
      insufficiency. Phase III clinical development is ongoing. Preliminary data
      indicate efficacy of the drug administered once a month either subcutaneously or
      intravenously. To date, the safety profile appears consistent with that of other
      ESAs. Even if antibodies against Hematide develop during treatment in some
      patients, they do not cross-react with EPO. No cases of pure red cell aplasia
      have been described to date.

PMID- 21082944
TI  - Pathogenesis and management of myeloma bone disease.
AB  - Osteolytic bone disease is a frequent complication of multiple myeloma, resulting
      in skeletal complications that are a significant cause of morbidity and
      mortality. It is the result of increased activity of osteoclasts that is not
      followed by reactive bone formation by osteoblasts. Recent studies have revealed
      novel molecules and pathways that are implicated in osteoclast activation and
      osteoblast inhibition, including the RANKL/osteoprotegerin pathway, macrophage
      inflammatory proteins and the wingless type signaling pathway. These molecules
      also appear to interfere with tumor growth and survival, providing possible
      targets for the development of novel drugs for the management of lytic disease in
      myeloma. Currently, bisphosphonates are the mainstay of treatment for myeloma
      bone disease, although several novel agents appear promising. This review focuses
      on recent advances in understanding the biology of bone disease in multiple
      myeloma, diagnosis and recent progress in treatment options.

PMID- 21082945
TI  - Potential of mTOR inhibitors as therapeutic agents in hematological malignancies.
AB  - Despite significant advances in the treatment of hematological malignancies over
      the last decade, morbidity and mortality from these disorders remain high. New
      discoveries in the pathogenesis of these malignancies have led to better
      understanding of these diseases and new thinking in drug development. mTOR is a
      downstream effector of the PI3K/Akt (protein kinase B) signaling pathway that
      mediates cell survival and proliferation and is known to be deregulated in many
      cancers. Preclinical activity of mTOR inhibitors has been very promising in
      various hematological malignancies. Rapamycin analogs with relatively favorable
      pharmaceutical properties, including temsirolimus (CCI-779), everolimus (RAD001)
      and deforolimus (AP23573), are under clinical evaluations in patients with
      hematologic malignancies. They have shown encouraging results thus far and a
      favorable toxicity profile. Their utility, mainly as cytostatic agents, needs to
      be further explored in combination with pre-existing chemotherapeutic agents for
      various hematological malignancies.

PMID- 21082946
TI  - Role of microRNAs in hematological malignancies.
AB  - microRNAs (miRNAs) are short noncoding RNAs that function as post-transcriptional
      negative regulators of gene expression. They have been shown to be involved in
      the control of cell proliferation and differentiation, as well as acting as
      oncogenes or tumor-suppressor genes, suggesting their involvement in cancer
      development and progression. Expression profiles of human miRNAs have shown that
      many of them are aberrantly expressed in hematological malignancies. Therefore,
      miRNA profiling may be useful to distinguish between normal and tumor cells, and
      to create signatures for a variety of leukemia subtypes. Here, we review recent
      evidence for the involvement of miRNAs in the pathogenesis of different
      hematopoietic malignancies and their potential applications in diagnosis,
      prognosis and therapy of human leukemia.

PMID- 21082947
TI  - Transplantation for non-Hodgkin lymphoma.
AB  - High-dose therapy followed by autologous hematopoietic stem cell transplantation
      (auto-HCT) has become the treatment of choice for patients with relapsed
      aggressive non-Hodgkin lymphoma (NHL). However, relapse remains the most common
      cause of treatment failure after auto-HCT. More intensive regimens incorporating
      radioimmunotherapy into high-dose regimens have been developed to prevent
      relapse. The role of auto-HCT for follicular lymphoma and mantle cell lymphoma
      remain inconclusive. Since prognosis of patients with peripheral T-cell lymphoma,
      not otherwise specified are very poor with conventional chemotherapy, auto-HCT
      during first remission is being explored in peripheral T-cell lymphoma. Given the
      lower risk of relapse after allogeneic HCT (allo-HCT) in NHL, allo-HCT has been
      performed in patients with refractory or relapsed NHL, especially after auto-HCT
      failure. However, the transplant-related mortality remains high after
      myeloablative allo-HCT. Reduced-intensity conditioning followed by allo-HCT has
      been shown to reduce transplant-related mortality but graft-versus-host disease
      continues to be the major problem, thus the role of allo-HCT in NHL remains an
      investigational approach for NHL. The outcomes of auto-HCT and allo-HCT for
      various lymphomas are reviewed.

PMID- 21082948
TI  - Immunoregulation of GVHD by triggering the innate immune system with CpG.
AB  - Stimulation of Toll-like receptors by oligodeoxynucleotide sequences containing a
      CpG motif provides signals capable of triggering the innate and adaptive immune
      systems, thereby leading either to stimulation or suppression of
      immunoreactivities. Similar immunoregulatory capabilities are necessary for
      achieving the fine balance between engraftment and graft-versus-host disease
      required in the setup of allogeneic cell therapy. Ligation of CpG to its Toll
      like receptors can be accomplished by treatment of the host or pretransplant
      treatment of the donor in vivo. These different strategies are presented in this
      review, which summarizes the attempts to maximize beneficial alloreactivity
      against malignant or other undesirable host cells, while controlling graft-versus
      host disease.

PMID- 21082949
TI  - Current strategies for the management of children with sickle cell disease.
AB  - Children with sickle cell disease may present to doctors anywhere in the world.
      In developed countries, neonatal screening allows early identification and
      management of the disease, mostly through daily antibioprophylaxis, immunizations
      and education of the parents. Stroke prevention relies on the detection of high
      risk patients by annual transcranial Doppler ultrasonography from 2 to 16 years
      of age. Annual check-ups aim to detect early organ deficiencies. The most
      frequent complications are pain, infections and acute anemia; they may occur in
      combination. Approximately 10% of children have severe sickle cell disease that
      may require chronic blood transfusion, hydroxyurea or hematopoietic stem cell
      transplantation. Comprehensive management programs have dramatically increased
      survival, and most patients now reach adulthood.

PMID- 21082951
TI  - Hepatosplenic T-cell lymphoma and TNF-alpha inhibitors.

PMID- 21082953
TI  - Use of posaconazole in the treatment of invasive fungal  infections.
AB  - The emergence of invasive fungal infections as an increasingly important clinical
      problem in immunocompromised patients highlights the need for more effective
      antifungal agents and better strategies for prevention, diagnosis and treatment.
      Posaconazole is an extended-spectrum triazole with broad activity against a
      variety of fungal pathogens, both yeasts and molds. In particular, it has
      activity against several emerging pathogens, such as the Zygomycetes, which are
      resistant to many currently available antifungals, making it an attractive agent
      for use in both prophylactic and therapeutic situations. Studies demonstrating
      the prophylactic utility of posaconazole in neutropenic patients with acute
      myelogenous leukemia or myelodysplastic syndrome, and in patients with graft
      versus-host disease following allogeneic stem cell transplantation has led to the
      approval of the drug in the USA. These data have been reviewed elsewhere in
      detail. Published data on posaconazole as primary antifungal therapy are very
      limited, although there is a considerable amount of experience with the drug in
      the salvage setting following failure of or intolerance to other antifungal
      agents. In this review we will focus on the use of posaconazole for treatment of
      established invasive fungal infections, with a focus on opportunistic infections
      in immunocompromised patients.

PMID- 21082955
TI  - Transfusion medicine education session.
AB  - The European Haematology Association annual meeting is the second largest
      conference organized specifically for hematologists. This meeting report gives an
      overview of one particular session within this meeting, that of the transfusion
      medicine subject speciality, which included two speakers from the USA and one
      from the UK. The following lectures will be reviewed here: Jo-Ann Moulds-
      Transfusion policies and practices in alloimmunized sickle cell patients; Derwood
      Pamphilon--Transfusion problems in stem cell transplant patients; and Naomi Luban
      -Transfusion issues in neonatal and pediatric hematology. The session, therefore,
      included a significant discourse in clinical practice of transfusing the
      difficult to transfuse patient.

PMID- 21082954
TI  - Temsirolimus for the treatment of mantle cell lymphoma.
AB  - Although recent progress has been made in the treatment of mantle cell lymphoma
      (MCL) the majority of patients experience relapse and ultimately die of their
      disease. The translocation t(11;14) is a prerequisite for the diagnosis of MCL
      and results in overexpression of cyclin D1. Its protein translation is controlled
      by mTOR, a key element of the PI3K/Akt pathway, and mTOR constitutes an
      attractive therapeutic target. Temsirolimus, a specific inhibitor of mTOR, has
      been evaluated in two Phase II trials in patients with relapsed MCL, and
      promising response rates up to 40% were found. Subsequently, a randomized Phase
      III trial was initiated, in which superiority in remission induction and
      progression-free survival could be demonstrated for a regimen of temsirolimus 175
      mg for 3 weeks, followed by a 75-mg weekly application in comparison with
      established agents. This adds temsirolimus to the therapeutic armamentarium for
      the treatment of MCL. Further developments target combination therapy in MCL and
      other lymphoid neoplasms.

PMID- 21082956
TI  - 38th Annual Meeting of the International Society of Experimental Hematology.
AB  - The International Society of Experimental Hematology holds its annual meeting
      every northern summer. This year the meeting comprised of eight plenary sessions
      with distinguished invited speakers on in vivo imaging and tracking of
      hematopoietic stem cells (HSCs), HSC niches, epigenetic regulations of stem cells
      and regulation of stem cell fate, leukemogenesis, and mesenchymal stem cells. The
      small size of the meeting (300 attendees) permitted excellent discussion and face
      to-face contacts between students, junior scientists and experts. Owing to the
      large number of keynote speakers, this report focuses on the most novel,
      unpublished data presented during the meeting.

PMID- 21082957
TI  - Environmental-mediated drug resistance: a target for multiple myeloma therapy.
AB  - Multiple myeloma is an incurable malignancy of mature clonal B cells. The
      refractory nature of this disease has long been attributed to the acquisition of
      drug resistance. Traditionally, mechanisms of drug resistance have been defined
      by genetic, acquired changes in the expression or function of specific genes
      products. However, over the past 10 years a large body of evidence has emerged
      demonstrating that in addition to mechanisms of drug resistance intrinsic to the
      cancer cell, there exist dynamic, de novo mechanisms coordinated by the tumor
      microenvironment resulting in a environmental-mediated drug resistance (EM-DR).
      Within this review we will provide an overview of some of these mechanisms of
      drug resistance and how they contribute to minimal residual disease and
      subsequent treatment failure. By understanding mechanisms of EM-DR, therapeutic
      targets can be identified and interventions designed to reduce minimal residual
      disease and improve clinical outcomes.

PMID- 21082959
TI  - Autologous hematopoietic stem cell transplantation in autoimmune diseases.
AB  - The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical
      manifestations and, possibly, biological features vary widely. The results of
      conventional treatment are considered unsatisfactory in aggressive forms, with
      subsets of patients having short life expectancies. Relying on wide experimental
      evidence and more feeble clinical data, some research groups have used autologous
      hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune
      diseases with the aim of resetting the patient's immune system. Immunoablative
      conditioning regimens are preferred over their myeloablative counterparts, and
      some form of in vivo and/or ex vivo T-cell depletion is generally adopted.
      Despite 15 years' experience, published controlled clinical trials are still
      lacking, with the evidence so far available coming from pilot studies and
      registry surveys. In multiple sclerosis, clinical improvement, or at least
      lasting disease stabilization, can be achieved in the majority of the patients;
      nevertheless, the worst results are observed in patients with progressive
      disease, where no benefit can be expected from conventional therapy. Concerning
      rheumatologic diseases, wide experience has been acquired in systemic sclerosis,
      with long-term improvements in cutaneous disease being frequently reported,
      although visceral involvement remains unchanged at best. Autografting has proved
      to be barely effective in rheumatoid arthritis and quite toxic in juvenile
      idiopathic arthritis, whereas it leads to clinical remission and the reversal of
      visceral impairment in the majority of patients with systemic lupus
      erythematosus. A promising indication is Crohn's disease, in which long-term
      endoscopic remission is frequently observed. Growing experience with autologous
      HCST in autoimmune diseases has progressively reduced concerns about transplant
      related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained
      complete remission seems to be within the reach of autografting in some
      autoimmune diseases; in others, the indications, risks and benefits of
      autografting need to be better defined. Consequently, the search for new drugs
      should also be encouraged.

PMID- 21082960
TI  - Mobilization of hematopoietic stem cells into the peripheral blood.
AB  - Hematopoietic stem cells can be mobilized out of the bone marrow into the blood
      for the reconstitution of hematopoiesis following high-dose therapy. Methods to
      improve mobilization efficiency and yields are rapidly emerging. Traditional
      methods include chemotherapy with or without myeloid growth factors. Plerixafor,
      a novel agent that disrupts the CXCR4-CXCL12 bond, the primary hematopoietic stem
      cell anchor in the bone marrow, has recently been US FDA-approved for mobilizing
      hematopoietic stem cells in patients with non-Hodgkin lymphoma and multiple
      myeloma. Plerixafor and myeloid growth factors as single agents appear safe to
      use in family or volunteer hematopoietic stem cells donors. Plerixafor mobilizes
      leukemic stem cells and is not approved for use in patients with acute leukemia.
      Patients failing to mobilize adequate hematopoietic stem cells with myeloid
      growth factors can often be successfully mobilized with chemotherapy plus myeloid
      growth factors or with plerixafor and granulocyte colony-stimulating factor.

PMID- 21082962
TI  - Iron overload in myelodysplastic syndromes.

PMID- 21082958
TI  - Acute myeloid leukemia stem cells: seek and destroy.
AB  - Most adult patients with acute myeloid leukemia (AML) die from their disease.
      Relapses are frequent even after aggressive multiagent chemotherapy and
      allogeneic stem cell transplantation. AML is a biologically heterogeneous
      disease, characterized by frequent cytogenetic abnormalities and an increasing
      spectrum of genetic mutations and molecular aberrations. Laboratory data suggest
      that AML originates from a rare population of cells, termed leukemic stem cells
      (LSCs) or leukemia-initiating cells, which are capable of self-renewal,
      proliferation and differentiation. These cells may persist after treatment and
      are probably responsible for disease relapse. This review will describe bench and
      translational research in LSCs and discuss how the data should be used to change
      the direction of developmental therapeutics and clinical trials in AML.

PMID- 21082963
TI  - Effective pain management in hematological malignancies.

PMID- 21082965
TI  - Role of platelet counts in the management of essential thrombocythemia:
      experience with anagrelide.
AB  - An elevated platelet count is the hallmark of essential thrombocythemia (ET).
      Therapeutic control of platelet counts in ET has proven effective for minimizing
      the risk of bleeding complications. By contrast, the relationship between
      platelet count and thrombotic complications is less well defined. The beneficial
      effects of lowering the platelet count are greatest when levels are reduced close
      to or within the normal range, thus supporting the trend within the medical
      community to reduce platelet treatment targets to below 400-450 * 10(9)/l.
      Platelet counts have further utility in ET as a marker to indicate
      intolerance/resistance to hydroxyurea according to recently published guidelines.
      In the current era, where novel risk factors for ET complications are being
      discussed, this article takes a back-to-basics approach, considering what
      platelet counts reveal in practice as a risk factor for complications and a
      marker of treatment efficacy, with particular focus on data for the platelet
      selective agent anagrelide.

PMID- 21082967
TI  - Frontline autologous stem cell transplantation for peripheral T-cell lymphoma.
AB  - Peripheral T-cell lymphoma constitutes a heterogeneous group, with a low
      incidence and no standard frontline therapy. The current study evaluates the use
      of frontline autologous stem cell transplantation in 83 peripheral T-cell
      lymphomas included in the first and largest prospective trial. Results indicate
      that the procedure is feasible, with a low treatment-related mortality, and is
      associated with a better outcome than obtained with conventional chemotherapy. A
      general problem in this and other prospective trials is that approximately 30% of
      cases do not receive transplantation owing to disease progression. Thus, new
      approaches aimed at increasing the number of chemosensitive patients should be
      found, some of which are discussed in this article. For chemoresistant or
      relapsing patients, promising results have been reported using allogeneic stem
      cell transplantation or adding new agents.

PMID- 21082966
TI  - Voriconazole: a broad-spectrum triazole for the treatment of invasive fungal
      infections.
AB  - Over the last 20 years, the frequency of life-threatening, invasive fungal
      infections has risen dramatically, corresponding to an increase in the number of
      immunocompromised patients. Thus, the development of newer, better tolerated,
      more effective antifungal drugs has become critically important. Voriconazole was
      the first second-generation triazole to be approved by the US FDA and the EMEA,
      both in 2002. Voriconazole is currently approved for the treatment of invasive
      aspergillosis, candidemia, candidal esophagitis and disseminated candidiasis in
      adults, and serious fungal infections due to Scedosporium apiospermum and
      Fusarium species. In addition to providing an alternative treatment option for
      Candida infections and many emerging and refractory invasive fungal infections,
      voriconazole is currently the treatment of choice for invasive aspergillosis.
      Voriconazole has excellent in vitro activity against a wide spectrum of yeasts
      and molds, with only a few notable exceptions. Although it has the potential for
      some unique and interesting side effects, as well as important drug-drug
      interactions, the use of therapeutic drug monitoring can be used to optimize its
      efficacy and safety.

PMID- 21082968
TI  - PET imaging in lymphoma.
AB  - PET has become a cornerstone procedure in modern lymphoma management. This paper
      reviews, from a clinical point of view, the evidence for using PET in the
      different subtypes of lymphoma and the different steps of their management. The
      reader is given an overview of the current PET-based interventional lymphoma
      trials and an insight into possible future developments in the field, including
      new PET tracers.

PMID- 21082969
TI  - Follicular lymphoma: the case for timely intervention.
AB  - After decades of slow progress in the management of follicular lymphoma (FL),
      important strides are occurring. An aim for cure is realistic and appropriate for
      some patients, including those with stage I-II disease, some histologic subtypes
      of FL (e.g., FL grade 3b) and even some relapsing patients following allogeneic
      stem cell transplantation approaches. Survival outcomes are improving, probably
      in large part related to the inclusion of anti-CD20 monoclonal antibodies in
      current treatment strategies.

PMID- 21082970
TI  - Optimal treatment for relapsing patients with Hodgkin lymphoma.
AB  - Relapsed or refractory classical Hodgkin lymphoma (HL) remains a therapeutic
      challenge. Patients with relapsed HL should be identified according to their
      prognostic factors at relapse (duration of remission and extranodal disease or
      stage). Patients with refractory disease, defined as progression during induction
      treatment or within 90 days after the end of treatment, have the worst prognosis.
      Following non-crossresistant salvage chemotherapy to achieve cytoreduction, high
      dose therapy (HDT) and autologous stem cell transplantation has been shown to be
      better than conventional-dose chemotherapy for first-relapse/refractory HL. For
      patients with very unfavorable relapse or primary refractory HL, outcome remains
      poor with HDT. For these patients, the role of tandem HDT or allogeneic stem cell
      transplantation will be discussed. In this setting, novel investigational
      treatments will be presented.

PMID- 21082971
TI  - New mechanisms of resistance in Philadelphia chromosome acute lymphoblastic
      leukemia.
AB  - The outcome for adults and children with Philadelphia chromosome acute
      lymphoblastic leukemia (ALL) has been improved dramatically with the use of
      tyrosine kinase inhibitors but relapse is an expected event in the majority of
      patients. We reviewed recent findings obtained from both gene-expression
      profiling analysis and single nucleotide polymorphism arrays and characterized by
      the identification of multiple novel genetic alterations targeting key cellular
      pathways, including lymphoid differentiation, cell cycle, tumor suppression,
      apoptosis and drug responsiveness. By gene-expression profiling analysis a new
      subtype known as 'BCR-ABL1-like' was identified, which includes 15-20% of all
      precursor B-ALL cases and is associated with an unfavorable outcome. By single
      nucleotide polymorphism array analysis, deletions of genes such as IKAROS, PAX5
      and CDKN2A-CDKN2B were frequently identified. New therapeutic approaches are now
      available, such as dasatinib, nilotinib and bosutinib, and we highlight those
      that may be applicable to the treatment of adult BCR-ABL1-positive ALL.

PMID- 21082972
TI  - Clinicobiologic importance of cytogenetic lesions in chronic lymphocytic
      leukemia.
AB  - Molecular cytogenetic lesions play a major role in the pathogenesis of chronic
      lymphocytic leukemia (CLL) and represent important prognostic markers. Besides
      FISH, conventional banding analysis using effective mitogens is important for an
      accurate assessment of the cytogenetic profile of CLL. The most frequent
      aberrations are represented by 13q-, 11q-, +12, 6q- and 14q32/IGH translocations
      and 17p-. Chromosome translocations and complex karyotype may occur in up to 30
      and 16% of the cases, respectively. The frequency of 17p- and 11q- is higher in
      patients requiring treatment and in relapsed/refractory patients, reflecting the
      association of these rearrangements with unfavorable prognosis. Mutations of the
      TP53 gene may also confer an inferior outcome, as is the case with 14q32
      translocations and unbalanced translocations. Evidence was provided that distinct
      treatment approaches may be effective in specific cytogenetic entities of CLL,
      making molecular cytogenetic investigations a necessary tool for a modern
      diagnostic work-up in CLL.

PMID- 21082973
TI  - The impact of hematopoietic stem cell transplantation on the management of
      thalassemia.
AB  - Transplantation remains the only cure currently available for patients with
      thalassemia. Results of transplantation in this disease have steadily improved
      over the last two decades due to improvements in preventive strategies, effective
      control of transplant-related complications and development of new preparative
      regimens. High-resolution HLA typing has enabled physicians to perform
      transplants from unrelated volunteer donors for thalassemia with results
      comparable to those obtained employing an HLA-identical sibling. The
      probabilities for obtaining thalassemia-free survival after transplantation from
      an HLA-identical donor, family member or matched unrelated donor are between 85
      and 87%. Therefore, when an HLA-identical donor is present, the transplantation
      of allogeneic stem cells should be performed as allogeneic gene therapy.

PMID- 21082975
TI  - Classification and response criteria in mastocytosis: is there a need to revise?

PMID- 21082976
TI  - Risk of childhood leukemia after low-level exposure to ionizing radiation.

PMID- 21082979
TI  - Fermented papaya preparation for beta-thalassemia?
AB  - This article comments on the results obtained by Fibach et al., which showed
      reduction of oxidative status in red blood cells of patients with beta- and E
      beta-thalassemia (beta-thal) treated with fermented papaya preparation. The study
      was a three-center, prospective study, including eight patients with beta-thal
      intermedia, four beta-thal major and seven E-beta-thal patients. The patients
      received 3 g of fermented papaya preparation (FPP) two- to three-times a day
      after meals, respectively, for 3 months. A marked decrease in reactive oxygen
      species, lipid peroxidation and phosphatidylserine externalization and an
      increase in GSH were detected in both groups of patients, indicating that FPP is
      efficient in reducing the oxidative stress of these red blood cells. The results
      are very encouraging as all parameters analyzed indicated the reduction of red
      blood cells oxidative stress by the action of a natural and inexpensive product.

PMID- 21082977
TI  - Hydroxyurea use in sickle cell disease: the battle with low prescription rates,
      poor patient compliance and fears of toxicities.

PMID- 21082980
TI  - Polyphosphates: a link between platelet activation, intrinsic coagulation and
      inflammation?
AB  - Early evidence has already shown that activated platelets play a role in the
      intrinsic pathway of coagulation, but the mechanism remained unclear. The finding
      that the dense granules of platelets contain polyphosphate (polyP), which has
      procoagulant effects, resolved this missing link between activated platelets and
      coagulation. PolyP secreted from platelets leads via activation of Factor XII to
      in vivo thrombin and fibrin formation. The relative importance of polyP in the
      process and stages of thrombus formation will require further investigation. In
      addition to its role in coagulation, polyP-induced Factor XII activation mediates
      the release of the inflammatory mediator bradykinin by activating the kallikrein
      kinin system. This results in vascular leakage and edema formation in vivo.
      Together, polyP release from platelets has a physiological role in the thrombus
      forming process, as well as in inflammatory reactions.

PMID- 21082981
TI  - Allogeneic immunotherapy to optimize the graft-versus-tumor effect: concepts and
      controversies.
AB  - This article focuses on the recent evolution of novel conditioning regimens in
      combination with adoptive cellular therapy in the allogeneic transplant setting
      for hematologic malignancies. Building on data from animal models, the field of
      allogeneic transplantation is undergoing a paradigm shift toward
      immunosuppressive regimens with less toxicity that allow donor hematopoietic
      engraftment in order to provide a graft-versus-tumor effect as the primary goal
      of transplantation, rather than chemoablation. In addition, the strategies
      described in this article, including the use of T-cell subsets as adoptive
      therapy, will apply to a much broader pool of patients than traditional
      transplant approaches, thereby allowing more patients with life-limiting
      illnesses, previously deemed ineligible, to pursue therapy with curative intent.

PMID- 21082982
TI  - CXCL12 and CXCR4 in bone marrow physiology.
AB  - This article discusses the multiple roles of CXCL12 and its receptor, CXCR4, in
      bone marrow (BM) hematopoietic stem cell (HSC) development and regulation. CXCL12
      interaction with CXCR4 results in effects as varied as cell migration,
      proliferation and survival or apoptosis. The selective signaling pathways that
      mediate these varied outcomes are summarized briefly. The CXCL12/CXCR4 pair is
      crucially involved in homing and repopulation of HSCs in the specific BM niches.
      Mechanisms of HSC mobilization to the peripheral circulation in response to
      physiological requests and therapeutic stimulations, as well as recent data on
      the novel receptor for CXCL12, CXCR7, are reviewed.

PMID- 21082983
TI  - JAK2 V617F and beyond: role of genetics and aberrant signaling in the
      pathogenesis of myeloproliferative neoplasms.
AB  - Dysregulated signaling is a hallmark of chronic myeloproliferative neoplasms
      (MPNs), as evidenced by the identification of the activating JAK2 V617F somatic
      mutation in almost all patients with polycythemia vera (PV) and 50-60% of
      essential thrombocythemia and primary myelofibrosis patients. These disorders are
      clinically distinct, raising the question of how a single mutation can result in
      such phenotypic diversity. Mouse models have demonstrated that the level of JAK2
      V617F expression can modulate the phenotype, and clinical studies of JAK2 V617F
      allele burden have reported similar findings. It has also been hypothesized that
      one or more pre-JAK2 V617F events may modify the MPN phenotype. However, the
      molecular basis of JAK2 V617F-negative essential thrombocythemia and primary
      myelofibrosis remains largely unexplained. Mutations in the TET2 gene have been
      identified in both JAK2 V617F-positive and -negative MPNs and other myeloid
      neoplasms, but their functional and clinical significance have yet to be
      clarified. In addition, recent reports have identified a specific germline
      haplotype that increases the predisposition to MPNs. The role of inhibitory
      pathways (e.g., SOCS and LNK) in regulating JAK-STAT signaling in MPNs is being
      increasingly recognized. The implications of these findings and their clinical
      relevance are the focus of this article.

PMID- 21082984
TI  - Novel treatment regimens for Waldenstrom's macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is a B-cell lymphoproliferative disorder
      defined by bone marrow infiltration by lymphoplasmacytic cells as defined by the
      current classification systems. According to its transition situation between
      mutated chronic lymphocytic leukemia and multiple myeloma, several new
      therapeutic alternatives have been proposed for this entity based on the
      experience with these two well-known conditions together with the highly singular
      data provided by preclinical models. Thus, in WM two main therapeutic attitudes
      are possible: the use of conventional therapies based on the administration of
      single drugs or combinations with alkylating agents, purine analogues and anti
      CD20 monoclonal antibodies; or the use of very new combinations that, without
      rejecting the previously mentioned drugs, include new agents, such as proteasome
      inhibitors, immunomodulatory agents or even histone deacetylase inhibitors and
      PI3K/AKT inhibitors, among others. Here we review the most recent results
      reported for the use of new combinations and new drugs in patients with WM at
      different stages of the disease.

PMID- 21082987
TI  - Platelets and angiogenesis: novel aspects.

PMID- 21082985
TI  - Novel oral anticoagulants. Part II: direct thrombin inhibitors.
AB  - The quest for an ideal anticoagulant is ongoing. Oral agents that do not require
      blood level monitoring are presently undergoing taut scrutiny for efficacies and
      potential side effects, and could soon be ready to transform the history of
      coagulation medicine. The first part of this article (published in last month's
      Expert Review of Hematology) embraced a comprehensive review of oral Factor Xa
      inhibitors, such as rivaroxaban, apixaban, eribaxaban, edoxaban, YM150. This
      second part of the article reviews novel oral direct thrombin inhibitors, such as
      dabigatran and AZD0837, and a brief description of oral Factor IXa inhibitors,
      such as TTP889.

PMID- 21082989
TI  - Eculizumab opens a new era of treatment for paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening and
      debilitating disorder of hematopoiesis. The only curative treatment is allogeneic
      stem cell transplantation. Other treatments are generally supportive in nature.
      Recently, eculizumab, as a targeted, disease-modifying treatment, was approved by
      the US FDA and the European Commission. Eculizumab is a humanized monoclonal
      antibody that inhibits complement factor C5. It is the first approved drug that
      specifically inhibits complement. This article presents the major aspects of PNH
      that are necessary to understand the mechanism of action of eculizumab.
      Experience from the pilot study and the Phase III pivotal program of eculizumab
      in PNH will be summarized and the impact of eculizumab on the future treatment of
      PNH will be discussed.

PMID- 21082990
TI  - Lestaurtinib: a multi-targeted FLT3 inhibitor.
AB  - Internal tandem duplication mutations of FMS-like tyrosine kinase-3 (FLT3) have
      been associated with poor outcomes in acute myelogenous leukemia. Over the course
      of the last several years, multiple agents have been developed and studied as
      potential inhibitors of FLT3 with the hope of providing clinical benefit for
      these patients. Lestaurtinib, a multi-targeted indolocarbazole derivative that
      potently inhibits FLT3 autophosphorylation in vitro, has been the most
      extensively studied agent in clinical trials to date. Multiple late-phase trials
      are underway to study this agent in adult and pediatric leukemia. This article
      will summarize the historical development of the pharmacology of lestaurtinib, as
      well as the ongoing investigation of the agent in preclinical and clinical
      studies.

PMID- 21082991
TI  - Adult T-cell acute lymphoblastic leukemia: prognostic impact of myeloid
      associated antigens.
AB  - Despite the recent improvement in the treatment of the disease, the prognosis of
      adult T-cell acute lymphoblastic leukemia (T-ALL) remains poor. In the last
      several decades, many reports analyzed clinical and/or biological factors in
      order to identify prognostic parameters suitable for risk stratification of T-ALL
      patients. The article under review analyzed the prognostic impact of myeloid
      associated antigen expression in a monocentric cohort of adult T-ALL patients.

PMID- 21082992
TI  - Autologous transplant for primary mediastinal B-cell lymphoma.
AB  - Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of lymphoma that
      shares similarities with diffuse large B-cell lymphoma and with classic Hodgkin's
      lymphoma. The current study evaluates the use of autologous stem cell transplant
      (ASCT) as part of initial therapy in a cohort of patients with PMBCL treated
      between 1985 and 2006. The study demonstrates excellent survival and progression
      free survival for patients in complete remission (CR) at ASCT, and for those
      achieving CR after ASCT. It also shows a benefit to administration of involved
      field radiation therapy. However, front-line therapy has evolved considerably
      since these patients were treated. Dose-dense chemotherapy regimens show
      excellent results without transplant and the incorporation of rituximab in the
      treatment may have further improved outcomes. Given these excellent results, ASCT
      should not currently be used in patients in first CR, but ASCT remains the
      treatment of choice in relapsed and refractory PMBCL. Similarly, radiotherapy is
      unnecessary in patients in first CR but is probably useful in patients with
      residual active mass.

PMID- 21082993
TI  - Atherosclerosis, venous thromboembolism and migraine: what are the associated
      risks?
AB  - There is a certain amount of literature suggesting that migraine is indirectly
      linked to an enhanced risk of atherosclerosis. Unfortunately, however, no
      explanation or true confirmation of this association has been provided. A recent
      study suggested that the burden of atherosclerosis at carotid and femoral
      arteries does not differ between migrainous and nonmigrainous patients, although
      there is an increased risk of venous thromboembolism in migrainous patients. No
      link between atherosclerosis and migraine was apparent, but the association
      between migraine and venous thrombolism requires further investigation. Some
      hypotheses on this complex issue are discussed in this article.

PMID- 21082994
TI  - Treatment options for essential thrombocythemia and polycythemia vera.
AB  - Polycythemia vera and essential thrombocythemia are the most common chronic
      myeloproliferative neoplasms; their molecular basis has been appreciated only
      recently and is briefly discussed in this article. Major causes of morbidity and
      mortality are represented by arterial and venous thrombosis, as well as by
      evolution to myelofibrosis or transformation to acute leukemia. Therapy is
      currently aimed at reducing the rate of thrombosis without increasing the risk of
      hematologic transformation that might be caused by exposure to cytotoxic drugs. A
      risk-oriented approach is employed for stratifying patients to the most
      appropriate therapeutic options. However, results of clinical trials with
      interferon, and the expected effects of novel drugs selectively targeting the
      abnormal pathways that are involved in the clonal myeloproliferation, are pushing
      therapeutic goals from disease control only to cure. These different issues, and
      current recommendations for treatment, will be discussed in the review.

PMID- 21082995
TI  - Leukotriene pathway in sickle cell disease: a potential target for directed
      therapy.
AB  - Sickle cell disease (SCD) is characterized by recurrent episodes of vaso
      occlusion, resulting in tissue ischemia and end-organ damage. Inflammation is
      critical to the pathogenesis of vaso-occlusion and has been associated with SCD
      related morbidity and mortality. Despite the impact of inflammation, no directed
      anti-inflammatory therapies for the treatment or prevention of vaso-occlusive
      events currently exist. Among individuals with SCD, asthma is a comorbid
      inflammatory condition that increases the risk of pain episodes, acute chest
      syndrome and death. Inflammation associated with asthma could augment the
      proinflammatory state of SCD, increasing episodes of vaso-occlusion. Leukotrienes
      are inflammatory mediators that play a prominent role in the pathogenesis of
      asthma and have been associated with SCD-related morbidity. Targeting
      inflammatory mediators, such as leukotrienes, is a promising approach for the
      development of novel therapies for the treatment of SCD. This review will examine
      the relationship between inflammation and vaso-occlusion, with particular focus
      on the leukotriene pathway.

PMID- 21082996
TI  - Health-related quality of life and symptom assessment in patients with
      myelodysplastic syndromes.
AB  - Health-related quality of life (HRQOL), symptom burden and other types of patient
      reported outcomes have acquired an important role in clinical research, as they
      can provide precious information on the patient's perspective of disease symptoms
      and treatment-related effects. HRQOL in patients with myelodysplastic syndromes
      (MDSs) may be compromised for several reasons, including severe anemia, the
      frequent occurrence of infections and the need for blood transfusions. Many MDS
      patients are elderly patients who might present with comorbidities from the time
      of diagnosis. Our investigation started with a systematic search of the
      literature in which prospective studies were identified and evaluated according
      to a predefined coding scheme. Both HRQOL outcomes and traditional clinical
      reported outcomes were systematically analyzed. Overall, we found nine
      prospective studies, four of which evaluated HRQOL in a randomized controlled
      trial setting and, interestingly, all these studies were published after the year
      2001, possibly reflecting a recent interest in HRQOL research in MDS patients.
      While methodological drawbacks were identified, mainly in terms of small sample
      size and amount of missing data, HROQL assessment has been shown to be feasible
      in MDS patients and there are excellent examples of how this approach can provide
      additional key outcomes. A good example is the important evidence emerging from
      two recent randomized controlled trials that HRQOL benefits are obtained with
      azacitidine and decitabine compared with supportive care. In view of the enormous
      potential of patient-reported outcome assessment in providing valuable outcomes
      in support of clinical decision-making, its implementation in future studies of
      MDS patients is strongly recommended.

PMID- 21082997
TI  - Suboptimal responses in chronic myeloid leukemia: milestones and mechanisms.
AB  - Patients with chronic myeloid leukemia who fail to achieve timely treatment
      responses have a worse prognosis. Although many patients respond well to first
      line treatment with imatinib, a significant proportion relapse or experience an
      inadequate response. Since effective alternative Bcr-Abl inhibitors are available
      (i.e., dasatinib or nilotinib), several regional groups have proposed milestones
      for imatinib failure or suboptimal response based on the achievement of specified
      levels of response within a defined treatment duration. A suboptimal response
      indicates that, although patients may continue to receive a benefit from
      continuing imatinib treatment at the assigned dose, long-term outcome may be
      better with an alternative strategy. The underlying mechanisms behind suboptimal
      responses are multifactorial and may differ from those causing relapse.

PMID- 21083001
TI  - Expert Review of Hematology: addressing the needs of a broad research field.

PMID- 21082998
TI  - Role of gene-expression profiling in chronic myeloid leukemia.
AB  - Gene-expression profiling enables disease classification and risk stratification,
      and provides important insights into possible pathogenetic mechanisms. The
      clinical management and prognosis of chronic myeloid leukemia (CML) has
      substantially changed after the introduction of targeted therapies, such as
      imatinib and the second-generation tyrosine kinase inhibitors nilotinib and
      dasatinib. Although exact characterization of CML pathogenetics has been
      performed by showing the causal pathogenetic relevance of the reciprocal
      translocation between chromosomes 9 and 22 for CML development, the disease still
      exhibits a marked clinical and biological heterogenicity. Thus, prognostic scores
      for a more exact disease classification, as well as for prediction of response to
      tyrosine kinase inhibitor therapy are warranted, especially because scores
      established within the interferon era have lost their prognostic value when
      applied to patients treated with imatinib. Gene-expression profiling has been
      proven to represent a powerful tool for early identification of nonresponders to
      cancer therapy. Several profiling studies in CML have been reported thus far.
      However, the available data are inconsistent, which is mainly due to technical
      reasons, such as the use of various different chips, different biostatistical
      algorithms for data analysis and, most importantly, the use of various different
      cellular sources (i.e., mononuclear cells from peripheral blood, whole bone
      marrow cells or selected bone marrow-derived stem/progenitor cells). This review
      will summarize the recent literature on gene-expression profiling for CML
      classification and response prediction.

PMID- 21083002
TI  - Sex differences in thrombosis.

PMID- 21083004
TI  - Role of bortezomib for the treatment of previously untreated multiple myeloma.
AB  - Although multiple myeloma remains an incurable disease, its management has
      changed recently with the introduction of novel agents, including bortezomib.
      Several pilot studies and two randomized trials have evaluated the role of
      bortezomib-based combinations as induction therapy in myeloma patients who are
      candidates for transplant, showing high efficacy (>80% response rate with 20-30%
      complete remission), which increased after autologous stem cell transplant. In
      addition, in patients who are not candidates for transplant, bortezomib in
      combination with melphalan and prednisone has also been found to be superior to
      conventional therapy, with high overall and complete response rates; responses
      were rapid and durable and there was a significant prolongation in time to
      progression and overall survival. Moreover, bortezomib has broad utility since
      its efficacy is not influenced by the presence of poor prognostic features, such
      as high-risk cytogenetic abnormalities, renal impairment or advanced age. These
      results allow bortezomib-based combination therapy to be established as key
      options for patients with previously untreated multiple myeloma.

PMID- 21083005
TI  - Nilotinib for the treatment of chronic myeloid leukemia.
AB  - The introduction of targeted therapy has revolutionized the treatment of chronic
      myeloid leukemia (CML). The pivotal role of the Philadelphia chromosome,
      resulting from the breakpoint cluster region-Abelson (BCR-ABL) translocation, led
      to the development of imatinib mesylate, a tyrosine kinase inhibitor with
      significant activity against the BCR-ABL oncoprotein. Unprecedented clinical
      activity in CML led to rapid approval and established first-line therapy with
      imatinib mesylate as the standard of care in most patients. However, the
      occurrence of imatinib resistance or intolerance has sparked the development of
      newer drugs with increased activity or specificity. Nilotinib is a second
      generation tyrosine kinase inhibitor that has been rationally designed on the
      basis of imatinib. An overview is given on clinical results in imatinib-resistant
      or -intolerant patients that led to its current approval as second-line therapy
      for the chronic and accelerated phases of CML. Future studies will address the
      role of nilotinib as first-line therapy, in combination strategies and in the
      context of specific BCR-ABL mutations.

PMID- 21083006
TI  - Role of allogeneic transplantation in chronic myeloid leukemia.
AB  - The use of allogeneic hematopoietic stem cell transplantation for the treatment
      of chronic myeloid leukemia (CML) patients has changed dramatically during the
      past decade. It was the standard of care for all younger CML patients with a
      compatible donor before the introduction of imatinib. It is used now as a rescue
      treatment for patients for whom tyrosine kinase inhibitors have failed. Both
      treatments, tyrosine kinase inhibitors and allogeneic transplantation, are very
      powerful and able to control the disease in the long-term. It is therefore of
      great importance to know the place of each therapy and to integrate allogeneic
      hematopoietic stem cell transplantation in a risk-adapted way into the treatment
      plan of each individual patient.

PMID- 21083007
TI  - Hodgkin's lymphoma: current treatment strategies and novel approaches.
AB  - Approximately 80% of Hodgkin's lymphoma (HL) patients achieve long-term remission
      after primary chemotherapy or chemo/radiotherapy. Despite these excellent
      results, further treatment improvement is necessary. HL therapy is associated
      with severe acute and long-term toxicities. Thus, a major aim of clinical HL
      research is to evaluate novel schemes that are less toxic than current standard
      regimens without being less effective. Another focus is the treatment of patients
      with multiple relapses. Standard treatment for these patients has not yet been
      defined, and their prognosis is still poor. Reduced-intensity conditioning
      allogeneic stem cell transplantation was recently shown to be effective in
      carefully selected young chemosensitive patients. Furthermore, new strategies
      such as antibody- and small-molecule-based therapy have demonstrated encouraging
      results in preclinical studies and the first clinical trials.

PMID- 21083008
TI  - Risk of heparin-induced thrombocytopenia in patients receiving
      thromboprophylaxis.
AB  - Heparin-induced thrombocytopenia (HIT) is a clinicopathological syndrome
      associated with heparin therapy that is characterized by a decrease in platelet
      counts and/or the development of a new thrombosis. Two types of HIT exist, type I
      is nonimmune and self-resolves, whereas type II is immune-mediated and clinically
      important. The formation of antibodies against the platelet factor 4-heparin
      complexes results in platelet activation and thrombin formation, which lead to an
      increased risk of thrombosis. Unfractionated heparin is associated with a higher
      risk of HIT than low-molecular-weight heparins. Surgical patients, particularly
      those undergoing orthopedic or cardiac surgery, are at higher risk of HIT than
      medical patients. Treatment of HIT involves heparin cessation together with
      anticoagulation with direct thrombin inhibitors or indirect factor Xa inhibitors.

PMID- 21083011
TI  - Individualizing treatment for Waldenstrom's macroglobulinemia.

PMID- 21083009
TI  - Transfusion medicine in trauma patients.
AB  - Injured patients stress the transfusion service with frequent demands for
      uncrossmatched red cells and plasma, occasional requirements for large amounts of
      blood products and the need for new and better blood products. Transfusion
      services stress trauma centers with demands for strict accountability for
      individual blood component units and adherence to indications in a clinical field
      where research has been difficult, and guidance opinion-based. New data suggest
      that the most severely injured patients arrive at the trauma center already
      coagulopathic and that these patients benefit from prompt, specific, corrective
      treatment. This research is clarifying trauma system requirements for new blood
      products and blood-product usage patterns, but the inability to obtain informed
      consent from severely injured patients remains an obstacle to further research.

PMID- 21083013
TI  - Clinical activity of laromustine (OnriginTM) in hematologic malignancies.
AB  - Laromustine (OnriginTM), formerly known as Cloretazine((r)) (VNP40101M), belongs
      to a novel class of alkylating agents--the sulfonylhydrazines--and was selected
      for clinical development based on its broad anti-tumor activity in preclinical
      models. Laromustine is metabolized to yield 90CE and methylisocyanate, the former
      rapidly produces an alkylating, chloroethylating species, similar to the
      chloroethylating species generated by carmustine. However, several features
      distinguish laromustine from carmustine and possibly account for their biological
      differences in vitro and in vivo. The chloroethylating species responsible for
      laromustine's alkylator effect is relatively specific for guanine and forms a
      crosslink after incorporation into DNA. Laromustine has significant activity in
      both older patients with previously untreated acute myeloid leukemia or high-risk
      myelodysplastic syndrome, including those with very poor-risk disease, and in
      patients with relapsed disease. Further clinical studies are required with
      laromustine to evaluate its place as an anticancer agent in other hematological
      malignancies.

PMID- 21083015
TI  - Antithrombin-alpha for the prophylaxis of venous thrombosis in congenital
      antithrombin deficiency.
AB  - ATryn((r)) is a transgenically produced recombinant antithrombin (AT) concentrate
      licensed in Europe and the USA for the thromboprophylaxis of hereditary AT
      deficient patients undergoing surgical procedures who are at a high risk of
      venous thromboembolism. It is also licensed, in the USA only, for prevention the
      of venous thromboembolism in association with delivery and the immediate post
      partum period. ATryn is administered as a continuous intravenous infusion, with
      weight-adjusted loading and maintenance dosing regimens. Recombinant AT has an
      identical amino acid structure with minor glycosylation differences to endogenous
      AT. ATryn has a shorter half-life but an equivalent efficacy to that of plasma
      derived AT concentrates in the prevention of venous thromboembolism in this rare
      distinct group with a high thrombotic risk. In addition, this recombinant product
      should be free from the risk of human viral or prion transmission.

PMID- 21083014
TI  - Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid
      leukemia.
AB  - The tyrosine kinase inhibitor imatinib mesylate (IM) set new standards in the
      treatment of chronic myeloid leukemia (CML). However, emergence of resistance to
      IM became a major therapeutic challenge. Bosutinib (SKI-606), a 7-alkoxy-3
      quinolinecarbonitrile, functions as a dual inhibitor of SRC and ABL kinases, and
      preclinical studies demonstrated a high antiproliferative activity in human and
      murine CML cell lines. In ongoing Phase I/II clinical trials, bosutinib yielded
      promising results revealing high clinical efficacy, good tolerability and reduced
      toxicity in IM-resistant or -intolerant CML patients. In this article, we provide
      an overview on the mechanism of action, and the preclinical and currently
      available clinical data for bosutinib. Owing to its favorable toxicity profile
      and its high antileukemic activity, bosutinib is a promising novel treatment
      option for patients with CML. A recently initiated, randomized open-label Phase
      III clinical study will clarify its role in first-line therapy of Philadelphia
      chromosome-positive chronic-phase CML.

PMID- 21083016
TI  - 2nd International Congress on Leukemia, Lymphoma and Myeloma.
AB  - The 2nd International Congress on Leukemia, Lymphoma and Myeloma (ICLLM) is a
      novel initiative of the Turkish Society of Hematology. The first congress was
      organized in Fethiye in May, 2007. After the success and positive impressions of
      the participants, the THD decided to organize the ICLLM every other year. The
      major focus was hematological malignancies, not only LLM, but also
      myeloproliferative disorders and myelodysplastic syndromes. The target audience
      was hematologists, oncologists and those involved in stem cell transplantation.
      The congress was held over 2 and a half days and attended by more than 350
      participants from 25 different countries. The scientific program was shaped by 12
      distinguished international speakers, who co-chaired and designed the sessions.
      The majority of the hematologists are caring for malignant patients and the
      Congress was a great opportunity for participants to get the latest update before
      the American Society of Clinical Oncology and American Society of Hematology 2009
      official meeting. The rising interest and encouraging increase in the number of
      participants geared us to announce the organization of 3rd ICLLM in May 2011 in
      Istanbul.

PMID- 21083017
TI  - Two faces for Janus: recombinant human erythropoiesis-stimulating agents and
      cancer mortality.
AB  - Untreated anemia in cancer patients has severe consequences for many organ
      systems. Erythropoiesis-stimulating agents (ESAs) are indicated for the treatment
      of chemotherapy-induced anemia in cancer patients. Several studies in patients
      with solid tumors have shown that these agents effectively increase hemoglobin
      levels, improve the quality of life and reduce the requirement for emergency
      blood transfusions, regardless of the type of concomitantly administered
      chemotherapy. The meta-analysis evaluates the impact of ESAs during the active
      study period on mortality and the overall survival during the longest available
      follow-up, irrespective of anticancer treatment, with little heterogeneity
      between trials. A total of 10,441 patients on chemotherapy were enrolled in 38
      trials. There was little evidence for a difference between trials of patients
      administered different anticancer treatments (p for interaction = 0.42). The meta
      analysis demonstrated that ESAs increased mortality by 17% during the active
      study periods and worsened overall survival in patients with cancer. However, 62%
      of patients evaluated in this analysis started the ESA therapy with basal
      hemoglobin values over that recommended by ASCO/ASH guidelines. However, the high
      quality of meta-analysis and the novelty of the information do not represent an
      obstacle for the continued the use of ESAs within the revised European
      Organisation for Research and Treatment of Cancer (EORTC) guidelines and the
      revised labels.

PMID- 21083019
TI  - Biology and treatment of follicular lymphoma.
AB  - Follicular lymphoma (FL) is the second most common lymphoid tumor. It is composed
      of elements resembling those of normal germinal centers. In particular, it is
      constituted by small centrocytes and large centroblasts, typically CD10+, CD19+,
      CD20+, CD79a+ and BCL6+, with follicular growth pattern. The molecular hallmark
      of FL is the t(14;18)(q32;q21) translocation, which leads to inappropriate BCL2
      expression. This feature, other than representing a pathogenetic primary event,
      constitutes a suitable diagnostic marker, as well as a target for minimal
      residual disease monitoring and, hopefully, future therapies. Clinically, FL
      presents with indolent behavior, characterized by prompt response to initial
      therapy but almost invariably subsequent relapses. Novel approaches, including
      stem cell transplantation, monoclonal antibodies and innovative agents, should be
      then considered for improving long-term results.

PMID- 21083020
TI  - Prognostic tools in follicular lymphomas.
AB  - Despite significant improvements in treatment modalities over the 10 years, the
      clinical course of patients with follicular lymphoma (FL) remains heterogeneous.
      Thus, prognostic indexes are still required to direct treatment choices and for
      the design of clinical trials. Investigators have conducted a variety of studies
      aimed at integrated assessment of biological and clinical features in order to
      identify novel prognostic factors and scoring systems. Genetic studies focused on
      tumor cells and the tumor microenvironment represent a step forward in
      understanding the biology of FL and are likely to provide new prognostic tools
      for future clinical use. Several prognostic factors have been identified and are
      currently used in combination to establish prognostic scores and to support
      therapeutic decisions. The FL International Prognostic Index (FLIPI) is currently
      used for defining individual risk of death. More recently, FLIPI2 was developed
      by the same group that built FLIPI as a new model for prognostic definition of
      patients with FL. The model was defined using prospectively collected data from
      patients who also received the monoclonal therapeutic antibody rituximab and
      stratifies patients into three risk categories for disease progression. Since
      many biological factors are not yet clinically validated or easily assessable,
      clinical data still represent the major source of prognostic information. The
      progressive development of new and more effective therapies for the treatment of
      FL makes the study of prognosis a dynamic and evolving area of clinical research.

PMID- 21083021
TI  - Prognostic molecular markers in myelodysplastic syndromes.
AB  - Cytogenetic findings in myelodysplastic syndromes play an important role in
      diagnosis, prognostication and clinical decision making. Therefore, they became
      an important aspect in scoring systems such as the International Prognostic
      Scoring System (IPSS) and the WHO-adapted Prognostic Scoring System (WPSS).
      Ongoing efforts to refine the categorization of karyotypes with regard to
      prognosis and therapeutic options will change scoring systems in the near future.
      In order to learn more about the pathophysiology of myelodysplastic syndromes,
      various molecular genetic aberrations are identified and their impact on
      prognosis discussed. New screening methods such as gene expression or single
      nucleotide polymorphism analysis are good candidates to find entrance in clinical
      practice in the future as they are useful tools in further elucidation of the
      underlying defects in myelodysplastic syndromes and the development of more
      specific classifications of the disease concerning risk assessment.

PMID- 21083022
TI  - Noninvasive approach for the management of hemolytic disease of the fetus.
AB  - Hemolytic disease of the fetus and newborn (HDFN) is due to maternal
      alloantibodies directed against paternally inherited antigens on fetal red cells,
      and it is still a problem in affected pregnancies despite the routine use of anti
      D immunoglobulin during pregnancy and shortly after delivery. The current
      noninvasive management of HDFN starts with the determination of fetal RhD
      genotype by use of cell-free fetal DNA in maternal plasma. When the fetus is
      antigen positive, the follow-up is performed by Doppler ultrasonography for the
      detection of moderate or severe anemia on the basis of an increase peak velocity
      of systolic blood in the middle cerebral artery. Finally, if anemia is suspected,
      an invasive approach is required in order to perform an intrauterine blood
      transfusion, which should only be attempted when the fetus needs transfusion.
      This approach reduces the iatrogenic conversion of mild-to-severe disease, which
      occurred as a result of the previous invasive management, and prevents
      unnecessary administration of human-derived blood products. These changes
      represent one of the genuine successes of fetal therapy.

PMID- 21083018
TI  - Adoptive T-cell therapy for B-cell malignancies.
AB  - The success of allogeneic hematopoietic cell transplantation (HCT) for B-cell
      malignancies is evidence that these tumors can be eliminated by T lymphocytes.
      This has encouraged the development of specific adoptive T-cell therapy, both for
      augmenting the anti-tumor effect of HCT and for patients not undergoing HCT. T
      cells that are capable of recognizing antigens expressed on malignant B cells may
      be recruited from the endogenous repertoire or engineered to express tumor
      targeting receptors. Critical insights into the qualities of T cells that enable
      their persistence and function in vivo have been derived, and obstacles to
      effective T-cell-mediated tumor eradication are being elucidated. These advances
      provide the tools to translate adoptive T-cell transfer into reliable clinical
      therapies.

PMID- 21083023
TI  - Late complications after hematopoietic stem cell transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to
      patients with leukemia, lymphoma and severe non-malignant diseases. More than
      40,000 HSCTs are performed annually worldwide. Therefore, the number of long-term
      survivors, free of the disease for which they were transplanted is continuously
      increasing. Despite the improved prognosis of HSCT, long-term outcome may be
      impaired by transplant-associated morbidity and mortality. Long-term survivors
      can present a variety of malignant and non-malignant complications, impairing
      physical and psychological performance, normal integration in family and social
      life, and quality of life. Conditioning regimens, particularly when including
      total-body irradiation as well as graft-versus-host disease, play a key role in
      the development of late effects. However, with increasing time since
      transplantation new types of late effects may emerge. Awareness on long-term
      effects after HSCT is crucial to provide adapted pretransplant counseling, and
      recommendations for post-transplant screening, prevention and early treatment.

PMID- 21083025
TI  - Have chemosensitizing strategies for multidrug-resistant childhood acute
      lymphoblastic leukemia come of age?

PMID- 21083026
TI  - Another blow to leukocyte antibody-mediated TRALI.

PMID- 21083028
TI  - Immunotherapy with histamine dihydrochloride for the prevention of relapse in
      acute myeloid leukemia.
AB  - Most patients with acute myeloid leukemia (AML) achieve complete remission (CR)
      after induction chemotherapy. Despite ensuing courses of consolidation
      chemotherapy, a large fraction of patients will experience relapses with poor
      prospects of long-term survival. Histamine dihydrochloride (HDC) in combination
      with the T-cell-derived cytokine IL-2 was recently approved within the EU as a
      remission maintenance immunotherapy in AML. HDC reduces myeloid cell-derived
      suppression of anti-leukemic lymphocytes, and aims to unravel a therapeutic
      benefit of IL-2 in AML by improving natural killer and T-cell activation. A
      randomized Phase III trial with 320 AML patients in CR demonstrated a significant
      reduction of relapse risk after immunotherapy with HDC plus low-dose IL-2 in the
      post-consolidation phase. HDC is the first approved therapeutic to target the
      state of immunosuppression in AML; further development in this area may comprise
      supplementary or alternative counter-suppressive agents with the aim to improve
      the efficacy of cancer immunotherapy.

PMID- 21083029
TI  - 50th Annual Scientific Meeting of the British Society for Haematology.
AB  - The 50th Annual Scientific Meeting of the British Society for Haematology was
      notable, not only for its golden anniversary, but also because it coincided with
      the eruption of the Icelandic volcano, Eyjafjallajokull, and the ensuing travel
      chaos. In total, 28 speakers from overseas were unable to reach Edinburgh,
      including a significant number of British speakers who were stranded. However,
      owing to the superb efforts of the conference organisers and Edinburgh
      International Conference Centre staff, teleconferencing equipment was installed
      and all speakers were contacted and able to give their talks on time. The
      program, consisting of simultaneous sessions and plenary lectures, covered not
      only recent advances in clinical and laboratory hematology, but also reflected on
      the contribution of British hematology to the international arena over the past
      50 years.

PMID- 21083030
TI  - Platelet dose for prophylactic platelet transfusions.
AB  - Although guidelines exist to deal with some aspects of platelet transfusion
      practice, many important clinical issues have not been addressed in large
      randomized controlled trials (RCTs). Slichter et al. conducted a RCT of
      prophylactic platelet transfusions to determine the effects of the dose of
      platelets on clinical signs of bleeding, the use of platelet and red cell
      transfusions, changes in the recipient's post-transfusion platelet count, days to
      next transfusion and adverse events (Effects of Prophylactic Platelet Dose on
      Transfusion Outcomes [PLADO] trial). The primary end point of the study (i.e.,
      the percentage of patients in each group with at least one episode of bleeding of
      grade 2 or higher according to the WHO criteria) was not significantly different
      (71, 69 and 70% of patients in the low-, medium- and high-dose group,
      respectively). According to these data, one can conclude that the dose of
      platelets transfused has no significant effect on the incidence of bleeding in
      patients with hypoproliferative thrombocytopenia and platelet counts no greater
      than 10 * 109/l.

PMID- 21083031
TI  - Notch signaling: from stem cell expansion to improving cord blood
      transplantation.
AB  - Ex vivo expansion of hematopoietic stem and progenitor cells has been a major
      goal for experimental hematologists and stem cell biologists during the last two
      decades. The clinical implications of such a procedure are obvious, considering
      the increasing interest in cell therapy protocols. This is particularly true in
      the setting of cord blood transplants, in which increased numbers of such
      primitive cells are needed. The study analyzed in this article indicates that by
      stimulating the Notch signal transduction pathway in primitive cord blood cells
      it is possible to significantly increase the numbers of both hematopoietic stem
      and progenitor cells. Furthermore, infusion of such expanded cells in patients
      receiving a cord blood transplant results in a significant reduction in the time
      to myeloid engraftment. The relevance of this study is twofold--on the one hand,
      it shows that the Notch pathway is involved in the expansion capacity of
      primitive hematopoietic cells in culture, and on the other hand, it indicates
      that ex vivo-expanded stem/progenitor cells can have a role in hematopoietic
      transplantation settings.

PMID- 21083032
TI  - (18)F-deoxyglucose PET: useful in the management of patients with stem cell
      transplantation for lymphoma?
AB  - (18)F-deoxyglucose (FDG) positron emission tomography (PET) and more recently FDG
      PET/computed tomography (CT) has become an important tool in the management of
      patients with Hodgkin and non-Hodgkin lymphoma. It adds metabolic and functional
      information to conventional anatomical imaging, mainly assessed by CT. Especially
      for the detection of early response to treatment and prognostic considerations,
      this type of information seems better suited than anatomical information.
      Consequently, the ability of FDG PET to predict the outcome in patients with stem
      cell transplantation (SCT) for lymphoma has been tested in several studies.
      Results in patients with autologous SCT have been promising, and pretransplant
      FDG PET is likely to become routine in this group of patients. The evaluated
      study investigates, for the first time, the predictive value of pretransplant FDG
      PET in allogeneic SCT, as well as the utility of FDG PET for the follow-up of
      these patients. All 80 patients included in the prospective study had reduced
      intensity conditioning. In contrast to FDG PET before autologous SCT, there was
      no correlation at all between pretransplant FDG PET results and the outcome after
      allogeneic SCT. This reflects the fact that other or additional reasons,
      especially the graft-versus-leukemia effect, are substantial for the outcome of
      allogeneic SCT in comparison with autologous SCT. Follow-up with FDG PET after
      reduced-intensity allogeneic SCT was significantly more sensitive than CT to
      detect disease progression or relapse, and was useful in guiding treatment in the
      situation of disease relapse.

PMID- 21083033
TI  - Genomic polymorphisms of the innate immune system and allogeneic stem cell
      transplantation.
AB  - Allogeneic stem cell transplantation (allo-HSCT) is largely employed for treating
      patients affected by many hematological disorders, but despite the considerable
      improvement in the treatment of its complications, graft-versus-host disease and
      infections remain important causes of morbidity and mortality. Innate immunity is
      crucial in the immune defense against infections after allo-HSCT, and in the
      biological reactions leading to graft-versus-host disease. Thus, the innate
      immune system plays an important role in allo-HSCT clinical outcome. It is known
      now that cytokine gene polymorphisms greatly influence the outcome of allo-HSCT.
      In addition, genetic variability of some pattern-recognition receptors and
      antimicrobial peptides represent a promising field to be researched for allo-HSCT
      impact. Furthermore, more recent work suggests the importance of genetic
      variability between donor and recipient in the killer cell immunoglobulin-like
      receptors of the natural killer cells on the allo-HSCT outcome. This article
      discusses the main cytokines and innate immune gene polymorphisms influencing
      allo-HSCT outcome, presents new innate immune genes with promising expectations
      and points at the importance of genetic variability in natural killer cells in
      allo-HSCT outcome.

PMID- 21083035
TI  - Genomic polymorphisms in sickle cell disease: implications for clinical diversity
      and treatment.
AB  - Sickle cell disease (SCD) is one of the best characterized human monogenic
      disorders. The development of molecular biology allowed the identification of
      several genomic polymorphisms responsible for its clinical diversity. Research on
      the first genetic modulators of SCD, such as coinheritance of alpha-thalassemia
      and haplotypes in the beta-globin gene cluster, have been followed by studies
      associating single nucleotide polymorphisms (SNPs) with variable risks for
      stroke, leg ulceration, pulmonary hypertension, priapism and osteonecrosis, with
      differences in the response to hydroxyurea, and with variability in the
      management of pain. Furthermore, multigenic analyses based on genome-wide
      association studies have shed light on the importance of the TGF-beta superfamily
      and oxidative stress to the pathogenesis of complex traits in SCD, and may guide
      future therapeutic interventions on a genetically oriented basis.

PMID- 21083034
TI  - Relapse after allogeneic stem cell transplantation.
AB  - Since allogeneic stem cell transplantation (SCT) represents an intensive curative
      treatment for high-risk malignancies, its failure to prevent relapse leaves few
      options for successful salvage treatment. While many patients have a high early
      mortality from relapse, some respond and have sustained remissions, and a
      minority has a second chance of cure with appropriate therapy. The prognosis for
      relapsed hematological malignancies after SCT depends on four factors: the time
      elapsed from SCT to relapse (with relapses occurring within 6 months having the
      worst prognosis), the disease type (with chronic leukemias and some lymphomas
      having a second possibility of cure with further treatment), the disease burden
      and site of relapse (with better treatment success if disease is treated early),
      and the conditions of the first transplant (with superior outcome for patients
      where there is an opportunity to increase either the alloimmune effect, the
      specificity of the antileukemia effect with targeted agents or the intensity of
      the conditioning in a second transplant). These features direct treatments toward
      either modified second transplants, chemotherapy, targeted antileukemia therapy,
      immunotherapy or palliative care.

PMID- 21083036
TI  - Transfusion-related acute lung injury: emerging importance of host factors and
      implications for management.
AB  - Recent insights from models of transfusion-related acute lung injury (TRALI), and
      from clinical reports, reveal that host factors are important in TRALI
      pathogenesis. Predisposing factors with lung neutrophil-priming capacity, such as
      sepsis and mechanical ventilation, increase susceptibility for a TRALI reaction,
      and can aggravate the course of disease. These findings may explain the higher
      incidence of TRALI in the critically ill compared with general hospital
      populations. The emerging importance of host factors may have implications for
      TRALI management. Suspected TRALI cases in which another acute lung injury risk
      factor is present (termed 'possible TRALI' in the consensus definition) should be
      reported to the blood bank, including patients suffering from an underlying
      condition. In reporting of TRALI cases, use of the international TRALI consensus
      definition should be used, rather then national TRALI scoring systems, to ensure
      a uniform approach, which may decrease variance in estimations of incidence. In
      terms of treatment of TRALI patients, there is a rationale to apply therapeutic
      strategies, which have proven to be beneficial in acute lung injury.

PMID- 21083037
TI  - Follicular lymphoma: emerging therapeutic strategies.
AB  - Follicular lymphoma is a diverse disease, both biologically and clinically.
      Patients may present with indolent, asymptomatic disease or more aggressive,
      symptomatic disease with high tumor burden. Decision-making to treat in the
      frontline is based on histology, disease burden and patient symptoms. The general
      approach should be a combination of rituximab and chemotherapy, traditionally
      using alkylating agents, with or without an anthracycline, with more recent
      evidence for the alternative of bendamustine. Relapsed/refractory follicular
      lymphoma carries similar variability in presentation. Therapeutic options include
      the same regimens traditionally used for first-line therapy; however, they also
      include agents, such as bendamustine, bortezomib, lenalidomide and anti-CD20
      agents (rituximab, ofatumumab and radioimmunotherapy). Finally, hematopoietic
      stem cell transplantation (both autologous and allogeneic) remains a useful
      treatment strategy, although the optimal timing of such approaches requires
      further clarification.

PMID- 21083038
TI  - Pathogenesis, classification and treatment of mastocytosis: state of the art in
      2010 and future perspectives.
AB  - Mastocytosis is a myeloid neoplasm characterized by abnormal accumulation and
      frequent activation of mast cells (MCs) in various organs. Organ systems
      typically involved are the bone marrow, skin, liver and gastrointestinal tract.
      In most adult patients, the systemic form of mastocytosis (SM) is diagnosed,
      which includes an indolent subvariant, an aggressive subvariant and a leukemic
      subvariant, also termed MC leukemia. Whereas in pediatric mastocytosis, which is
      usually confined to the skin, a number of different KIT mutations and other
      defects may be detected, the KIT mutation D816V is detectable in most (adult)
      patients with SM. In a subset of these patients, additional oncogenic factors may
      lead to enhanced survival and growth of MCs and, thus, to advanced SM. Other
      factors may lead to MC activation, with consecutive anaphylactic reactions that
      can be severe or even fatal. Treatment of SM usually focuses on symptom relief by
      histamine receptor antagonists and other supportive therapy. However, in
      aggressive and leukemic variants, cytoreductive and targeted drugs must be
      applied. Unfortunately, the prognosis in these patients remains poor, even when
      treated with novel KIT-targeting agents, polychemotherapy or stem cell
      transplantation. This article provides a summary of our knowledge on the
      pathogenesis and on treatment options in SM.

PMID- 21083042
TI  - Micro total analysis systems in biopharmaceutical process development.

PMID- 21083044
TI  - Young investigator: Noel Alex Gomes.

PMID- 21083045
TI  - Metabolites in safety testing.
AB  - Traditionally, only circulating concentrations of parent drug have been measured
      in the rodent and nonrodent test species used for drug safety assessments and
      served as an index of systemic exposure for comparisons to human exposures.
      Circulating concentrations of metabolites have generally only been measured in
      specialized circumstances (e.g., parent compound was extensively metabolized).
      Measurement of only the parent compound is usually sufficient when the metabolite
      profile in humans is similar to that in at least one of the animal species used
      in the nonclinical safety assessment. However, it is possible that metabolites
      formed in humans might not be present in the rodent and nonrodent test species
      used for drug safety assessments or the metabolites are formed at
      disproportionately higher concentrations in humans than in the animal test
      species. Generally, metabolites identified only in human plasma or metabolites
      present at disproportionately higher concentrations in humans than in any of the
      animal test species should be considered for safety assessment. The Center for
      Drug Evaluation and Research (CDER) published a Guidance for Industry on Safety
      Testing of Drug Metabolites that provides current thinking within CDER on the
      nonclinical safety assessment of human drug metabolites derived from drug
      products. The CDER guidance defines human metabolites that can raise a safety
      concern as those formed at greater than 10% of parent drug systemic exposure at a
      steady state. By contrast, the more recent International Conference on
      Harmonization: Guideline on Nonclinical Safety Studies for the Conduct of Human
      Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3[R2])
      describes the threshold as 10% of total drug-related exposure. Where they differ,
      the ICH guidance supersedes the CDER Guidance. The purpose of this article is to
      provide a perspective on the important details of these guidances from a
      regulatory review standpoint, as well as discuss some concerns that have arisen
      from the regulated industry regarding the CDER guidance. Such issues include
      parent drug that is extensively metabolized, metabolism by intestinal bacteria
      and metabolites formed by nonclinical test species but not humans.

PMID- 21083046
TI  - Introduction to calibration curves in bioanalysis.
AB  - Analytical standards are used in bioanalytical analysis for the quantitative
      measurement of large and small molecules in the pharmaceutical industry. This
      article will introduce the reader to the common, acceptable practices for the use
      of calibration curves in chromatographic and ligand-binding assays. The
      discussion presented is a combination of regulatory requirements and the authors'
      experience in performing bioanalysis. While all possible techniques are not
      covered, generally acceptable practices are described to serve as a starting
      point for novice practitioners.

PMID- 21083047
TI  - Two-step silylation procedure for the unified analysis of 190 doping control
      substances in human urine samples by GC-MS.
AB  - BACKGROUND: While a number of different derivatization procedures for screening
      GC-MS analysis of prohibited substances are followed by doping control
      laboratories, a unified derivatization procedure for the GC-MS analysis of 190
      different doping agents was developed. RESULTS: Following preliminary
      experiments, a two-step derivatization procedure was selected. The evaluation of
      various silylation parameters, such as reagent composition, reaction time,
      reaction temperature, catalysts and microwave oven reaction time, for this
      procedure was carried out. CONCLUSION: The suitability of the developed procedure
      was demonstrated through application on urine samples at concentration levels of
      the minimum required performance limit for all tested substances. This new
      derivatization procedure, which significantly decreases time and cost, is
      suitable for a routine basis application.

PMID- 21083049
TI  - Matrix effect elimination during LC-MS/MS bioanalytical method development.
AB  - Due to the presence of endogenous components in biofluids, ionization suppression
      or enhancement may occur for bioanalytical assays using LC-MS or LC-MS/MS
      technologies. The matrix effect may affect the precision and accuracy of a
      bioanalytical method and, therefore, compromise the quality of the results.
      Protein precipitation sample preparation along with LC-MS/MS is a high-throughput
      method most commonly used in bioanalysis and is largely affected by the matrix
      effect. In order to eliminate the matrix effect during the method development,
      some considerations may be used: cleaner sample preparations, more sensitive
      instruments, which allow less material to be injected, different chromatographic
      separations and much more must be investigated. More than giving tools to
      adequately assess the matrix effect during the method development, this review
      gives scientists numerous ways to eliminate or reduce the matrix effect based on
      novel sample-preparation techniques, new chromatographic optimization methods and
      new technologies.

PMID- 21083048
TI  - Micellar liquid chromatography in doping control.
AB  - The issue of doping control in sport involves the development of reliable
      analytical procedures and efficient strategies to process a large number of
      samples in a short period of time. Reversed-phase LC techniques with aqueous
      organic mobile phases and MS or diode-array detection yield satisfactory results
      for the identification of prohibited substances in sport. However, time-consuming
      sample pretreatment steps are required, which reduces sample throughput. Micellar
      LC (MLC) that uses hybrid mobile phases of surfactant above its critical micellar
      concentration and organic solvent has been revealed as an interesting
      alternative. The surfactant sodium dodecyl sulfate solubilizes the protein
      components of urine, serum and plasma, which permits their direct injection into
      the chromatographic system. Only dilution and filtering of the samples may be
      required. Most MLC analyses are performed in isocratic mode, with short retention
      times and good selectivity. The sensitivity of MLC allows the detection of a
      variety of doping substances at least 24-48 h after being administered.

PMID- 21083050
TI  - Chemiluminescent enzyme immunoassays: a review of bioanalytical applications.
AB  - This review gives an overview of the most recent and innovative developments in
      the field of chemiluminescent immunoassays through carefully selected examples.
      First, assays using microtiter plates for high-throughput or multiplexed assays
      aiming to achieve more complex assays through the multiplication of parameters
      per wells will be described. Systems will then be presented that have been
      recently developed, motivated by integration and miniaturization of existing
      immunoassays in more complex experimental setups. Finally, enhanced-performance
      chemiluminescent biochips, based on chemiluminescent reaction intensification,
      will be introduced.

PMID- 21083051
TI  - Strategies for electrochemical detection in immunochemistry.
AB  - In this review, the current status of research in electrochemical immunosensors
      is considered. We primarily focus on label-free and enzyme-labeled immunosensors,
      and the analytical capabilities of these devices are discussed. Moreover, the use
      of magnetic beads as new materials for immunosensors coupled with electrochemical
      sensing is also described, together with the application of new molecules such as
      aptamers as specific biorecognition elements. Examples of the applicability of
      these devices in solving various analytical problems in clinical, environmental
      and food fields are reported. Finally, the prospects for the further development
      of immunosensor technologies are shown.

PMID- 21083052
TI  - Microdosing: a valuable tool for accelerating drug development and the role of
      bioanalytical methods in meeting the challenge.
AB  - The concept of specifically determining the clinical pharmacokinetics of a
      compound using a very low nonpharmacologically active dose (microdose) with an
      abridged safety and chemistry, manufacturing and control package is relatively
      new. It is not without its controversy and it is still a subject of discussion.
      Here, the rationale and application of this approach are examined, together with
      the regulatory and bioanalytical framework. There are two bioanalytical methods
      commonly used for human microdosing studies: LC-MS/MS and accelerator MS (AMS).
      Each method has advantages and disadvantages with the choice of instrumentation
      being closely tied to the primary objective(s) of the study. If a rapid decision
      is required on the appropriateness of a pharmacokinetic profile or if a choice is
      needed from a series of compounds, especially before radiolabeled material is
      available, LC-MS/MS may be preferable. However, if extreme sensitivity is
      required, data are required on all drug-related material and metabolites, or a
      simultaneous intravenous microdose is used to determine absolute bioavailability
      (sometimes referred to as microtracing), AMS becomes the analytical method of
      choice. Examples are provided of microdosing studies utilizing both of these
      bioanalytical techniques. It is emphasized that microdosing is only one tool in
      the drug developer's tool box and it should be used in the context of all
      available data. However, when used appropriately, microdosing is a valuable tool,
      bridging between lead optimization and early clinical development.

PMID- 21083053
TI  - Nano-LC and HPLC-chip-ESI-MS: an emerging technique for glycobioanalysis.
AB  - In less than 5 years, an impressive number of methods based on nano-LC and HPLC
      chip coupled online to MS were developed and implemented to comprehensively
      address structural heterogeneity of glycoconjugates and glycans in biological
      matrices. C18, graphitized carbon and amide-based stationary phases were adapted
      to nanoflow level and on chip format, leading to improved sensitivity of
      structural analysis and superior level of information on highly complex glycan
      and glycoconjugate mixtures. This review offers a summary of the recent progress
      in the application of nano-LC and HPLC-chip-MS in glycoanalytics of
      glycopeptides, glycoprotein glycans, glycosaminoglycans, oligosaccharides and
      glycosphingolipids.

PMID- 21083054
TI  - Bioanalytical issues in patient-friendly sampling methods for therapeutic drug
      monitoring: focus on antiretroviral drugs.
AB  - Therapeutic drug monitoring is a way to pharmacokinetically guide drug therapy to
      assure a certain exposure to a drug when this exposure is related to treatment
      effectiveness or toxicity. Routinely, drug concentrations are measured in plasma
      obtained by venipuncture. However, venous sampling is difficult in some
      populations, such as neonates and patients suffering from phlebitis, and there
      may be logistical challenges, for example when nonhospital-based sampling is
      warranted (e.g., resource-limited settings). A proper bioanalytical method is
      crucial for measurements of drug level matrices suitable for patient-friendly
      drug monitoring. Special attention must be paid to bioanalytical methods in these
      patient-friendly matrices, since specific matrix-associated issues may have
      important implications. In this review, we will discuss these issues and give an
      overview of published bioanalytical methods with a focus on patient-friendly drug
      monitoring of antiretroviral drugs, where dried blood spots, hair and saliva have
      been the most important matrices for patient-friendly therapeutic drug
      monitoring. Furthermore, we will point out considerations for proper assay
      development and validation.

PMID- 21083057
TI  - Review of the 2008 European Medicines Agency concept paper on bioanalytical
      method validation.

PMID- 21083056
TI  - European Bioanalysis Forum and the way forward towards harmonized regulations.

PMID- 21083059
TI  - Young investigator: Jean-Nicholas Mess.

PMID- 21083060
TI  - Electrokinetic and hydrodynamic injection: making the right choice for capillary
      electrophoresis.
AB  - CE is a powerful liquid-phase separation technique that is an attractive
      alternative to HPLC because of its small sample requirements, high resolving
      power and excellent mass detection limits. While there are many similarities
      between the two techniques, there are also many differences, some obvious, some
      subtle. One of the often overlooked differences is the way sample is injected. In
      HPLC, injection is a very minor component of the method and the choice is
      predominantly restricted to the choice of solvent and the injection volume. But
      in CE, it is vastly more complex, and development of an appropriate injection
      strategy should be given consideration during any method development. While the
      choice between hydrodynamic or electrokinetic injection may not initially be
      given any thought, selection of the right approach for the right application can
      lead to significant improvements in performance, particularly with regard to
      achieving the lowest detection limits possible. The question is how to decide the
      best way to inject for each application?

PMID- 21083061
TI  - Detection of tetrahydrobiopterin by LC-MS/MS in plasma from multiple species.
AB  - BACKGROUND: Tetrahydrobiopterin (BH4) is a naturally occurring pteridine and
      cofactor for a variety of enzymes, including phenylalanine-4-hydroxylase, nitric
      oxide synthetase and glyceryl ether monooxygenase. BH4 is readily oxidized to
      dihydrobiopterin and biopterin (B), however only BH4 can provide proper cofactor
      functions. BH4 is the active ingredient in KuvanTM for the treatment of
      phenylketonuria. In order to measure BH4 in plasma from nonclinical and clinical
      samples with good accuracy, precision, sensitivity and robustness, an LC-MS/MS
      method was validated. To overcome the oxidation of BH4 in postcollection plasma,
      the approach was to measure the concentration of BH4 indirectly by measuring B
      concentration and applying an oxidation conversion ratio. Different endogenous
      levels of BH4 are determined in human, monkey, dog, rabbit, rat and mouse plasma.
      Furthermore, the conversion ratio of BH4 to B for each species is different and
      determined empirically. Plasma is transferred into cryogenic vials containing
      0.1% dithioerythritol to prevent oxidation of BH4. The samples are then extracted
      and oxidized under basic conditions. B is measured with LC-MS/MS using negative
      ion mode. RESULTS: The method is accurate, and precise to within 15%. The lower
      limit of quantitation in matrix is 5, 50 or 100 ng/ml, depending on the species
      endogenous levels of BH4. The pharmacokinetics of a single oral dose at three
      concentrations of BH4 administered to C57BL/6 mice is presented. In this mouse
      study, the T(1/2) of BH4 in plasma was approximately 1.2 h. CONCLUSION: The
      validated LC-MS/MS method to determine plasma BH4 concentration described herein
      has been used to support many nonclinical and clinical toxicokinetic and
      pharmacokinetic studies. BH4 is sensitive to oxidation and has a complicated
      biology. The method successfully supported the approval of Kuvan for the
      treatment of phenylketonuria.

PMID- 21083062
TI  - Rapid HPLC method for the simultaneous monitoring of duloxetine, venlaflaxine,
      fluoxetine and paroxetine in biofluids.
AB  - A simple and rapid HPLC method is developed for the determination of two
      serotonin-norepinephrine-reuptake inhibitors (duloxetine and venlaflaxine) and
      two selective serotonin-reuptake inhibitors (fluoxetine and paroxetine) in human
      biofluids. Separation was performed on an Inertsil ODS-3 column (250 x 4.0 mm, 5
      um) with acetonitrile-ammonium acetate (0.05 M, 41:59 v/v) at 235 nm, within 7
      min. SPE on Oasis((r)) HLB cartridges was applied for the isolation of analytes
      from biofluids. The developed methodology was validated in terms of sensitivity,
      linearity, accuracy, precision, stability and selectivity. Relative standard
      deviation was less than 10.4%. Limit of detection was 0.2-0.6 ng/ul in blood
      plasma and 0.1-0.8 ng/ul in urine. The method was successfully applied to
      biofluids from a patient under duloxetine treatment.

PMID- 21083063
TI  - Electrochemiluminescence in bioanalysis.
AB  - The discovery of electrochemiluminescence (ECL) and its development as a means of
      detection is truly a success story. Although studies describing ECL were
      published in the early 1960s, most studies using ECL as a means of detection were
      not widely published until the mid 1990s. Incorporating ECL into assays provides
      increased sensitivity, several logs of dynamic range and the ability to
      electronically control the reaction. These characteristics provide advantages
      over assays that rely on radioisotopic labels, fluorescence and enzymatic
      activity. There have been many areas of science that have benefited from the use
      of ECL, including environmental microbiology, virology, neurobiology, molecular
      biology and immunology. ECL has improved the understanding and treatment of
      infectious diseases, cancer, neurodegenerative diseases and even sleep apnea
      disorders. Drug development has also benefited from ECL via improved assessment
      of pharmacodynamics, pharmacokinetics and determining immune responses against
      protein-based therapeutics. This review provides an overview of ECL chemistry and
      principles with a more detailed emphasis on the applications of ECL-based assays
      in different areas of science and medicine. The primary purpose of this review is
      to provide an in-depth discussion of the impact that ECL-based analysis has had
      on microbiology, immunology, virology, neurodegenerative diseases, molecular
      biology and drug development. Examples of ECL-based bioanalysis in each of these
      fields are discussed in conjunction with an overview of ECL principles and
      instrumentation.

PMID- 21083064
TI  - 'False-positive' and 'false-negative' test results in clinical urine drug
      testing.
AB  - The terms 'false-positive' and 'false-negative' are widely used in discussions of
      urine drug test (UDT) results. These terms are inadequate because they are used
      in different ways by physicians and laboratory professionals and they are too
      narrow to encompass the larger universe of potentially misleading, inappropriate
      and unexpected drug test results. This larger universe, while not solely
      comprised of technically 'true' or 'false' positive or negative test results,
      presents comparable interpretive challenges with corresponding clinical
      implications. In this review, we propose the terms 'potentially inappropriate'
      positive or negative test results in reference to UDT results that are ambiguous
      or unexpected and subject to misinterpretation. Causes of potentially
      inappropriate positive UDT results include in vivo metabolic conversions of a
      drug, exposure to nonillicit sources of a drug and laboratory error. Causes of
      potentially inappropriate negative UDT results include limited assay specificity,
      absence of drug in the urine, presence of drug in the urine, but below
      established assay cutoff, specimen manipulation and laboratory error. Clinical
      UDT interpretation is a complicated task requiring knowledge of recent
      prescription, over-the-counter and herbal drug administration, drug metabolism
      and analytical sensitivities and specificities.

PMID- 21083065
TI  - Detection of doping with recombinant human growth hormone.
AB  - Detection of doping with recombinant human growth hormone is one of the
      challenges for antidoping analysis. This review focuses on the most important
      relevant publications that provide insight into the laboratory measurement of
      human growth hormone (hGH), antibodies and standards, the isoform approach and
      the biomarker approach. The isoform approach monitors the changes of hGH
      molecular isoform composition in serum and was applied at the Olympic Games in
      Athens in 2004, Turin in 2006 and Beijing in 2008. The markers approach detects a
      formula score, which reflects the changes in concentration of IGF-1 and P-III-P.
      All these methodologies measure the concentrations of growth hormone and its
      isoforms for isoform approach, or the concentrations of IGF-1 and P-III-P. All
      factors that affect these measurements should be taken into account for the
      development of methods to detect doping with recombinant hGH.

PMID- 21083066
TI  - Bioanalytical methods for the determination of cocaine and metabolites in human
      biological samples.
AB  - Determination of cocaine and its metabolites in biological specimens is of great
      importance, not only in clinical and forensic toxicology, but also in workplace
      drug testing. These compounds are normally screened for using sensitive
      immunological methods. However, screening methods are unspecific and, therefore,
      the posterior confirmation of presumably positive samples by a specific technique
      is mandatory. Although GC-MS-based techniques are still the most commonly used
      for confirmation purposes of cocaine and its metabolites in biological specimens,
      the advent of LC-MS and LC-MS/MS has enabled the detection of even lower amounts
      of these drugs, which assumes particular importance when sample volume available
      is small, as frequently occurs with oral fluid. This paper will review recently
      published papers that describe procedures for detection of cocaine and
      metabolites, not only in the most commonly used specimens, such as blood and
      urine, but also in other 'alternative' matrices (e.g., oral fluid and hair) with
      a special focus on sample preparation and chromatographic analysis.

PMID- 21083067
TI  - Retrospective drug detection in cases of drug-facilitated sexual assault:
      challenges and perspectives for the forensic toxicologist.
AB  - Reported incidences of drug-facilitated sexual assault (DFSA) are on the increase
      worldwide. These cases represent a particular challenge for the forensic
      toxicologist due to the difficulty in obtaining adequate evidence of drug
      administration. Primarily, this is due to the nature and diversity of the drugs
      involved, their pharmacology and sampling timescales. Evaluating whether a drug
      has been administered to a victim for the purpose of sexual assault can often be
      difficult, if not impossible. This review draws attention to this burgeoning
      crime and focuses on the unique challenges DFSA cases present in terms of
      evidential analysis. Current analytical methodologies for investigating DFSA are
      highlighted and discussed along with developments in improving analytical
      procedures. In particular, enlarging detection windows by adopting emerging LC-MS
      techniques is also discussed. This review also highlights the use of cutting-edge
      technologies such as ultra-HPLC and the use of alternative matrices for
      addressing the problem of improved retrospective drug detection.

PMID- 21083069
TI  - Impact of the recession on bioanalysis.

PMID- 21083071
TI  - Young investigator: Lianrong Wang.

PMID- 21083072
TI  - Research Spotlight: New multiparameter bioanalytical technologies for
      applications in personalized medicine, drug discovery and fundamental biology.
AB  - The ability to determine expression levels of multiple genetic and/or proteomic
      signatures simultaneously from the same sample volume is of tremendous importance
      in a wide range of biomedical applications, including disease diagnostics, drug
      discovery and fundamental studies of complex biological processes. Unfortunately,
      many of the tremendously enabling genomic and proteomic technologies available to
      the academic are not applicable in the clinical setting. Combining traditional
      chemical and biological insight with cutting-edge concepts from materials
      science, physics and engineering, our group brings an interdisciplinary approach
      to developing new tools in order to tackle longstanding refractory problems in
      the biological sciences - technologies that will enable fundamental biological
      discovery and, in some applications, expedite the transfer of biomolecular
      insight to the hands of the physician, where it can directly impact patient care.

PMID- 21083073
TI  - Incurred sample reproducibility: views and recommendations by the European
      Bioanalysis Forum.
AB  - Following intensive discussions, review, alignment of procedures and multiple
      surveys among their member companies, the European Bioanalysis Forum (EBF) is
      providing a recommendation on how to integrate incurred sample reproducibility
      (ISR) in the bioanalytical process. The recommendation aims to provide guidance
      throughout the lifecycle of a validated method, including the application of the
      method in study support. In its recommendation, the EBF considers both the
      internal discussions with EBF member companies, as well as the input provided in
      international meetings where ISR was discussed. The ultimate goal of the EBF
      recommendation is to ensure that bioanalytical methods can provide accurate and
      reproducible concentration data for pharmacokinetic and/or toxicokinetic
      evaluation, without any compromise, while safeguarding the optimal use of
      laboratory resources.

PMID- 21083075
TI  - GLP staff training, records and supporting documentation.
AB  - GLP is a government legislation that must be complied with when conducting safety
      studies for regulatory submission. The availability of documentation to verify
      the training and ability of staff employed in the laboratory is one of the
      requirements of this legislation. This article gives an overview of the use of
      training and training records in a bioanalytical laboratory. This article is
      designed to offer guidance to staff involved in GLP work and to outline some
      options with regard to the design of a training plan, recording of information,
      implenting training and reviewing records. However, the formal recording of
      training has benefits within any quality system, regardless of legislation.

PMID- 21083074
TI  - Assessing the matrix effects of hemolyzed samples in bioanalysis.
AB  - Validation of LC-MS/MS assays includes an assessment of matrix effects. Hemolysis
      effect, a special type of matrix effect, can also have an impact on analyte
      quantitation. In situations where the hemolysis effect is marginal, this can be
      resolved simply by dilution of hemolyzed samples with plasma prior to analysis.
      However, in some cases, the impact can be so dramatic that analytes are
      completely immeasurable. In such situations, modification to the bioanalytical
      method will be required, including, but not limited to, adjusting the
      chromatographic conditions to separate interferences present in hemolyzed
      samples; additional sample clean-up techniques such as protein precipitation in
      combination with SPE or a change in extraction technique such as from SPE to a
      liquid-liquid extraction method. Here, we report examples from four bioanalytical
      methods, where the presence of hemolyzed blood in plasma was found to have an
      impact on analyte quantitation and a description of the solutions adopted to
      resolve this are provided.

PMID- 21083076
TI  - Ultra-performance hydrophilic interaction LC-MS/MS for the determination of
      metformin in mouse plasma.
AB  - INTRODUCTION: Ultra-performance (UP) hydrophilic interaction LC (UPHILIC)
      interfaced with an ESI source and MS/MS was developed for the determination of
      metformin in mouse plasma samples. MATERIALS & METHODS: Several silica stationary
      phases under HILIC conditions were adapted to evaluate the retention mechanism
      profiles of the analyte. The influences of experimental factors such as the
      compositions of mobile phases on the chromatographic performance and the
      ionization efficiency of the test compounds in positive ion mode were
      investigated. The applicability of the proposed UPHILIC-MS/MS approach following
      a protein precipitation procedure for the quantitative determination of metformin
      at nanomole levels was examined with respect to assay specificity and linearity.
      RESULTS: The analytical results obtained by the described UPHILIC-MS/MS approach
      were found to be in good agreement with those obtained by an ion-pair UPLC-MS/MS
      method in terms of assay sample throughput, sensitivity and accuracy. CONCLUSION:
      The results suggested that it is feasible to convert a reversed-phase UPLC-MS/MS
      method to a UPHILIC-MS/MS method by simply switching the analytical columns while
      maintaining the rest of the experimental conditions for polar pharmaceutical
      analyses with enhanced retention and sensitivity.

PMID- 21083077
TI  - Analytical methods used in conjunction with solid-phase microextraction: a review
      of recent bioanalytical applications.
AB  - Integration of sampling and sample preparation with various analytical
      instruments is a highly desirable feature for any analytical method. This is most
      conveniently achieved by using microextraction techniques or various
      microdevices. Among these techniques, solid-phase microextraction (SPME) is
      particularly remarkable due to its simplicity and effectiveness. This review
      discusses the most recent applications of SPME in bioanalysis, grouped according
      to the analytical instrument that SPME is coupled to. It is shown that one of the
      most important aspects of such analytical methods is the ability of SPME to
      perform direct and selective extraction of analytes from complex biological
      samples. By far, the most popular method continues to be SPME coupled to GC.
      Nevertheless, the last 2 years have witnessed significant advances in other
      areas, such as successful automation of SPME coupled to liquid chromatography and
      the development of new coatings suitable for direct extraction from biological
      samples. Furthermore, a few bioanalytical applications based on direct coupling
      of SPME to MS, ion mobility spectrometry, CE and analytical chemiluminescence
      have been reported.

PMID- 21083078
TI  - Biomarkers: unrealized potential in sports doping analysis.
AB  - The fight against doping in sport using analytical chemistry is a mature area
      with a history of approximately 100 years in horse racing and at least 40 years
      in human sport. Over that period, the techniques used and the breadth of coverage
      have developed significantly. These improvements in the testing methods have been
      matched by the increased sophistication of the methods, drugs and therapies
      available to the cheat and, as a result, testing has been a reactive process
      constantly adapting to meet new threats. Following the inception of the World
      Anti-Doping Agency, research into the methods and technologies available for
      human doping control have received coordinated funding on an international basis.
      The area of biomarker research has been a major beneficiary of this funding. The
      aim of this article is to review recent developments in the application of
      biomarkers to doping control and to assess the impact this could make in the
      future.

PMID- 21083079
TI  - Stable isotope analysis of the bioelements: an introduction.
AB  - The abundances of the stable isotopes of the bioelements are not constant.
      Subtle, but significant, variations may be induced by physical, physiological and
      biochemical processes. These variations may be detected and quantified. Often,
      isotope fingerprints are characteristic of certain processes and may reveal
      information concerning the sources and origins of compounds of interest.
      Moreover, natural variabilities of stable isotopes may be exploited in order to
      perform tracer experiments. The most accurate technology to perform stable
      isotope analysis is (gas) isotope ratio MS (IRMS). Compound-specific approaches
      employ hyphenation of GC and LC to IRMS. In these approaches, complete conversion
      to simple gases prior to MS is required. Analysis by stable isotope ratio
      spectroscopy currently approaches the accuracy of IRMS. However, for
      bioanalytical projects, it is still predominantly confined to material
      synthetically enriched with stable isotopes.

PMID- 21083080
TI  - Mass spectrometric top-down analysis of proteins.
AB  - The comprehensive analysis of intact proteins down to the level of their
      individual amino acid sequence and the entirety of post-translational
      modifications is an area that can hardly be covered by the typical workflow in MS
      based protein analysis, which comprises enzymatic digestion, mass spectrometric
      analysis and subsequent database search. This approach typically provides 20-80%
      sequence coverage, which is not sufficient for the characterization of
      biopharmaceuticals, for example. This generates the requirement for a
      comprehensive analysis of the protein, without the risk of losing sequence
      information due to undetected peptides. Top-down sequencing of proteins starts
      from the intact protein, typically by determining the intact protein mass in the
      first step, a fragmentation of the intact protein is then performed within the
      mass spectrometer, resulting in fragment ions that allow us to pinpoint the
      protein sequence, as well as potential modifications or mutations in their
      localization and structure. A number of technologies have been developed for this
      task in the last few years, based on various different mass spectrometric
      instrument configurations, but typically based on the same technology platforms
      as used for bottom-up strategies. Thus, the use of one specific instrument often
      allows the application of top-down and bottom-up technologies in a complementary
      way, providing much more detailed information about the proteins of interest than
      either of the approaches alone.

PMID- 21083081
TI  - Industrialized MS-based proteomics in the search for circulating biomarkers.
AB  - Proteomics is the study of the expression, structure and function of proteins
      under a range of cellular conditions. A rapidly evolving component of this field
      is clinical proteomics, which focuses on proteins involved in human disease and
      how they are affected by therapeutic intervention. MS is the main analytical
      technology for identifying and quantifying proteins whose expression is modulated
      across the normal to disease continuum. Applying this technology to clinical
      samples, however, is particularly challenging due to high biological variability
      in the population, a variety of disease stages, nonuniform response to therapy,
      multiple concomitant treatments and special requirements for handling samples
      from clinical trials. Given these challenges, an 'industrialized' approach is
      best suited to clinical biomarker development, with its standard operating
      procedures, process control and 'chain of custody'. This review will focus,
      therefore, on MS-based industrialized proteomics for the discovery and
      verification of circulating candidate clinical protein biomarkers.

PMID- 21083083
TI  - Developing trends in bioanalysis.
AB  - The Forum, initiated over 30 years ago by Eric Reid of the University of Surrey,
      after whom the Forum is now named, is held in Guildford at the University of
      Surrey every 2 years. This year's forum was the 18th in the series. There were
      over 30 oral presentations and more than 20 posters, together with suppliers'
      exhibitions on Tuesday and Wednesday. At its inception, the title of Forum,
      maintained over the years, was chosen to emphasize the interactive nature of the
      meeting; somewhere that practical issues could be discussed and successes and
      failures, 'tricks' of the trade, surprises and problems where logic (initially)
      fails are shared. The on-campus format and evening social events provide plenty
      of opportunity to discuss unresolved problems in a 'convivial' atmosphere. There
      were three major themes to this year's Forum: interpreting and implementing
      'metabolites in safety testing'; quantification of biologicals (proteins and
      peptides, whether they be drugs, antidrug antibodies or biomarkers) in biological
      matrices using LC-MS/MS; and the use of dried blood spots. Interspersed among
      these were the core topics of the Forum, case histories illustrating the problem
      solving skills of the bioanalyst and their ability to cope with surprises.

PMID- 21083084
TI  - Generic approach to validation of small-molecule LC-MS/MS biomarker assays.
AB  - BACKGROUND: While the regulatory guidelines that describe the validation
      requirements for small molecules are very comprehensive, they are written
      primarily for xenobiotic drug molecules. However, the presence of endogenous
      analyte in control matrix presents an added analytical challenge that must be
      overcome if small-molecule biomarker assays are to be developed and
      characterized, especially where downregulation of analyte concentrations is
      expected. EXPERIMENTAL: A generic surrogate matrix calibration protocol has been
      successfully applied to the measurement of a number of small-molecule exploratory
      biomarkers using LC-MS/MS. The use of analyte-free matrix enables conventional
      calibration curves to be constructed across the anticipated range of sample
      concentrations. The evaluation of matrix effects is carried out using an
      experiment similar to the parallelism experiment used in ligand-binding assays.
      CONCLUSION: There is currently no published consensus approach to validation of
      small-molecule biomarker methods. This paper presents a generic approach to
      endogenous method validation for consideration as bioanalytical best practice for
      this type of assay.

PMID- 21083085
TI  - Critical comparison of MS and immunoassays for the bioanalysis of therapeutic
      antibodies.
AB  - Therapeutic antibody assessment in biofluids requires fit-for-purpose
      bioanalytical methods. The reference is the immunoassay, the accuracy of which
      may be compromised by interference by endogenous components. Here, we report the
      inherent analytical problems posed by immunoassays and propose an alternative
      based on LC-MS that should be readily applicable to the analysis of therapeutic
      antibodies in biological fluids. We review problems linked to assay sensitivity,
      the choice of the assay format involving either immunodetection or MS, and
      strategies in the assessment of bound versus free forms.

PMID- 21083086
TI  - Aerosol-based detectors for liquid chromatography: do they have a role in
      bioanalysis?

PMID- 21083089
TI  - Bioanalysis and Analytical Services Research Group at The Municipal Institute for
      Medical Research IMIM-Hospital del Mar, Spain.
AB  - Analytical laboratories involved in health-related research are becoming a
      fundamental part of the advancement of science in this field. Of particular
      interest to clinical, legal, toxicological, forensic and environmental matters is
      the analysis of drugs and medications present in biological fluids of consumers
      or exposed subjects. The established sensitive and reliable work of sports drug
      testing laboratories represents an interesting example of a multidisciplinarity
      approach toward widespread bioanalytical problems. The experiences reported in
      this article will be of general interest, especially for analysts studying the
      determination of substances in biological material.

PMID- 21083088
TI  - 10th Annual University of Wisconsin Land O'Lakes Bioanalytical Conference.
AB  - This conference was arranged by the Extension Services in Pharmacy at the
      University of Wisconsin School of Pharmacy. The purpose of this annual 4-day
      conference is to provide an educational forum to discuss issues and applications
      associated with the analysis of xenobiotics and metabolites in biological
      matrices. The conference is designed to include and encourage an open exchange of
      scientific and methodological applications for bioanalysis. To increase the
      interactive nature of the conference, the program will be a mixture of lectures,
      poster sessions, round table discussions and workshops. This paper summarizes the
      presentations at the Tenth Annual Conference.

PMID- 21083091
TI  - Criteria for selecting pharmacokinetic repeat study samples.
AB  - The pharmacokinetic (PK) repeat study sample, selected by the study
      pharmacokineticist, requires repeat bioanalysis because the concentration is
      incongruous with drug plasma concentration versus time profile. The inconsistency
      could be due to a number of reasons, including the detectable drug concentration
      in a predose sample or a sample from a placebo control group or a significant
      double peak in the terminal phase of an individual plasma concentration versus
      time profile that is not consistent with the profiles from other subjects in the
      same dose group. The justification for selecting the PK repeat sample should be
      clearly documented. The repeat analysis should be conducted in duplicate or
      triplicate as allowed by sample volume. To avoid subjectively selecting PK repeat
      samples, standard operating procedures should be prepared prior to the start of
      the study in order to define the criteria for selecting PK repeat study samples
      and also the procedure for conducting repeat analysis and reporting repeat assay
      values. The incurred sample re-analysis (ISR) assessment and the repeat analysis
      of pharmacokinetically anomalous samples are different in terms of purpose and
      conduct; the ISR assessment alone cannot accept or reject the results from a
      study for analytical reasons. Therefore, the results from the ISR assessment for
      assuring the reliability and reproducibility of a validated bioanalytical method
      in animal or human plasma or other biological matrices should not be used to
      substitute the results of repeat analysis of pharmacokinetically anomalous
      samples from a nonclinical or clinical study.

PMID- 21083092
TI  - Effect of high pH mobile phase on the sensitivity of multiple drugs by LC
      positive electrospray ionization MS/MS.
AB  - BACKGROUND: In this study, the postcolumn addition approach was used to evaluate
      the impact of high pH modifiers on the sensitivity of 25 compounds by LC-MS/MS
      under positive ESI (ESI+). RESULTS: None of the compounds were significantly
      suppressed by the use of high pH modifiers. Most of them showed a signal
      enhancement by at least twofold compared with acidic modifiers. The sensitivity
      gained under high pH mobile phase was used to develop a bioassay for the
      quantification of candesartan. The use of high pH mobile phase allowed for fast
      sample preparation that would have been impossible under typical low pH
      chromatography. CONCLUSION: We have shown that high pH modifiers are sufficient
      to induce a signal enhancement for the majority of compounds detected under LC
      ESI+-MS/MS.

PMID- 21083093
TI  - Multiplexed antibody arrays for the discovery and validation of glycosylated
      protein biomarkers.
AB  - Protein glycosylation, the enzymatic linkage of mono- and poly-saccharides to
      proteins, is a critical determinant of protein function; however, there is a lack
      of tools for studying the glycosylation of specific proteins in complex samples.
      A new type of antibody-lectin sandwich assay enables the measurement of the
      glycosylation of specific proteins that have been captured from complex samples
      using antibody arrays combined with lectin-based detection probes. Antibody
      lectin sandwich arrays have the potential to expand our understanding of the role
      of glycans and protein glycosylation in disease and to identify and investigate
      new biomarkers for early detection, disease prognosis and therapeutic response
      prediction. While antibody-lectin sandwich arrays yield less-detailed structural
      information regarding protein glycosylation than other available methods, they do
      provide a simple and reproducible method for investigating changes in protein
      abundance and glycosylation of multiple proteins and can be easily applied to
      large or small sample sets. By profiling protein and glycan variations, new
      disease-associated glycan alterations can be identified and validated for use as
      biomarkers.

PMID- 21083095
TI  - Method validation and application of protein biomarkers: basic similarities and
      differences from biotherapeutics.
AB  - Protein drug development and biomarkers share common bioanalytical technologies
      that are applied for different purposes. A fit-for-purpose approach should be
      used for biomarker assays at various stages of novel biomarker development and
      their application to drug development. Biomarker quantifications can be absolute
      or relative, depending upon the characteristics of the standard curve, which
      include the reference standard, substituted matrix and parallelism. Appropriate
      method-validation experiments should be carried out on sample collection,
      relative accuracy and precision, range finding, parallelism, selectivity,
      specificity and stability in order to meet the need for exploratory or advanced
      application that is specified for a study. The interaction of a biotherapeutic
      with the target ligand or inter-related biomarkers should be taken into
      consideration for method platform choice and validation. Direct adoption of
      commercial diagnostic kits can produce confounding data. Therefore, kit
      comparison, modification and appropriate validation experiments are often carried
      out to meet the specific purpose for drug development. Multiplex assays and
      physicochemical methods can complement the single-analyte ligand-binding assay
      for protein drugs and biomarkers.

PMID- 21083094
TI  - Mechanisms of amine accumulation in, and egress from, lysosomes.
AB  - The human body is continuously exposed to small organic molecules containing one
      or more basic nitrogen atoms. Many of these are endogenous (i.e.,
      neurotransmitters, polyamines and biogenic amines), while others are exogenously
      supplied in the form of drugs, foods and pollutants. It is well-known that many
      amines have a strong propensity to specifically and substantially accumulate in
      highly acidic intracellular compartments, such as lysosomes, through a mechanism
      referred to as ion trapping. It is also known that cells have acquired the unique
      ability to sense and respond to amine accumulation in lysosomes in an effort to
      prevent potential negative consequences associated with hyperaccumulation. We
      describe here methods that are used to evaluate the dynamics of amine
      accumulation in, and egress from, lysosomes. Moreover, we highlight specific
      proteins that are thought to play important roles in these pathways. A
      theoretical model describing lysosomal amine dynamics is described and shown to
      adequately fit experimental kinetic data. The implications of this research in
      understanding and treating disease are discussed.

PMID- 21083096
TI  - Tetrahydrogestrinone analysis and designer steroids revisited.
AB  - Anabolic steroids are the main abused class of prohibited substances in doping
      control. These steroids are associated with enhancement of muscular mass and
      aggressiveness, resulting in increased performance. Chromatography and MS have a
      key role among methods developed to detect anabolic steroids in doping control
      laboratories. However, the classical analytical approach fails in detection of
      the so-called 'designer steroids'. This review focuses on the rise of
      tetrahydrogestrinone, a drug that became synonymous with designer steroids. The
      reasons why classical methods fail in tetrahydrogestrinone detection are
      discussed and how the detection was implemented is shown. Alternative strategies
      for detection of new drugs designed to cheat current analytical methodology are
      highlighted. Concern for the abuse of veterinary designer drugs and supplements
      is also acknowledged.

PMID- 21083097
TI  - What are the obstacles for an integrated system for comprehensive interpretation
      of cross-platform metabolic profile data?

PMID- 21083099
TI  - 1st Australasian Symposium on Metabolomics.

PMID- 21083100
TI  - Recent developments in techniques and applications of metabolic profiling.

PMID- 21083101
TI  - First example of hepatocyte transplantation to alleviate ornithine
      transcarbamylase deficiency, monitored by NMR-based metabonomics.
AB  - We demonstrate the effective use of NMR spectroscopic profiles of urine and
      plasma from the first successful use of hepatocyte transplantation as a bridge to
      auxiliary partial orthotopic liver transplantation in a child antenatally
      diagnosed with severe ornithine transcarbamylase deficiency. In this single
      patient study, NMR profiles indicated that the disrupted urea cycle could be
      normalized by hepatocyte cell infusion and this was confirmed using orthogonal
      partial least-squares-based chemometrics. However, despite dietary manipulations
      and adminstration of ammonia scavengers, the desired reduction in plasma ammonia
      was not consistently achieved between sessions of hepatocyte transplantation due
      to episodes of sepsis. A subsequent liver transplant corrected the metabolic
      abnormalities. The use of metabolic profiling has been shown to be a promising
      method for evaluating the efficacy of cell infusions and has demonstrated the
      capability for the early detection of response to therapy in real time, an
      approach that may be of use in wider clinical settings.

PMID- 21083102
TI  - Nutrimetabolomics: development of a bio-identification toolbox to determine the
      bioactive compounds in grape juice.
AB  - BACKGROUND: Grape juice and related products have previously been associated with
      many health benefits, such as protection against cardiovascular disease. Current
      consensus is that the polyphenols are the likely bioactive species in these
      products. RESULTS: Extracts of commercially available grape juices exhibited
      biological antioxidant activities ranging from 19.30 to 3099.51 uM trolox
      equivalents, as determined by cell-based assay in which J774 macrophages were
      stimulated with lipopolysaccaride at a concentration of 100 ug/ml for 1 h.
      Partial least-squares regression was then used to determine covariance between
      the antioxidant activity and 400 MHz (1)H NMR spectral profiles using models with
      R(2)X and R(2)Y values of 0.64 and 0.95, respectively, using three latent
      variables: the Q(2)(cum) was 0.63. Hydroxycinnamic acids and their derivatives
      were identified as being the most positively correlated with the antioxidant
      activity. CONCLUSION: The work presented here describes a strategy for the
      bioinformatic linkage of plant metabolomic data with in vitro biological activity
      as an initial step towards determining structure-activity relationships.

PMID- 21083103
TI  - Simple data-reduction method for high-resolution LC-MS data in metabolomics.
AB  - BACKGROUND: Metabolomics LC-MS experiments yield large numbers of peaks, few of
      which can be identified by database matching. Many of the remaining peaks
      correspond to derivatives of identified peaks (e.g., isotope peaks, adducts,
      fragments and multiply charged molecules). In this article, we present a data
      reduction approach that automatically identifies these derivative peaks. RESULTS:
      Using data-driven clustering based on chromatographic peak shape correlation and
      intensity patterns across biological replicates, derivative peaks can be reliably
      identified. Using a test data set obtained from Leishmania donovani extracts, we
      achieved a 60% reduction of the number of peaks. After quality control filtering,
      almost 80% of the peaks could putatively be identified by database matching.
      CONCLUSION: Automated peak filtering substantially speeds up the data
      interpretation process.

PMID- 21083104
TI  - Spectroscopic and statistical methods in metabonomics.
AB  - Metabonomics is rapidly evolving through advances in analytical technologies
      together with the development of new hyphenated approaches that are increasingly
      being applied to analyze complex biological systems. Improvements in analytical
      performance, such as increased sensitivity and selectivity, are providing greater
      resolution to analytical datasets and the rich potential of metabonomics as a
      systems biology tool of choice is becoming clear. However, such improvements are
      resulting in datasets becoming increasingly demanding in terms of data handling
      and interpretation, and the degree to which metabonomics continues to develop
      will be dependent on how chemometrics and data-handling approaches keep pace with
      continually improving analytical technologies. This review provides an overview
      of the field of metabonomics, with a particular focus on the analytical
      techniques that are chiefly employed and the chemometric methods that have found
      most use. However, in addition, we mention less widely used analytical methods
      and suggest that advanced statistical methods will play a larger role in the
      future.

PMID- 21083105
TI  - Computational strategies for metabolite identification in metabolomics.
AB  - Most metabolomic data are characterized by complex spectra or chromatograms
      containing hundreds of peaks or features. While there are many methods for
      aligning or comparing these spectral features, there are few approaches for
      actually identifying which peaks match to which compounds. Indeed, one of the
      biggest unmet needs in the field of metabolomics lies in the problem of compound
      identification. This review describes some of the newly emerging computational
      strategies in metabolomics that are being used to aid in the identification of
      metabolites from biofluid mixtures analyzed by NMR and MS. The most successful
      compound-identification strategies typically involve matching spectral features
      of the unknown compound(s) to curated spectral databases of reference compounds.
      This approach is known as the identification of 'known unknowns'. However, the
      identification of truly novel compounds (the 'unknown unknowns') is particularly
      challenging and requires the use of computer-aided structure elucidation methods
      being applied to the purified compound. The strengths and limitations of these
      approaches as applied to different analytical technologies (GC-MS, LC-MS and NMR)
      will be discussed, as will prospects for potential improvements to existing
      strategies.

PMID- 21083106
TI  - NMR metabonomics for mammalian cell metabolism studies.
AB  - The detailed knowledge of mammalian cell metabolism and its adjustments to
      different cell properties and perturbations, such as disease and drug exposure,
      is of enormous value in the deeper understanding of pathological processes and
      drug mechanisms, as well as in the development of new and improved methods for
      diagnosis, follow-up of disease progression and treatment response. This review
      covers recent developments in the use of NMR-based metabonomics to characterize
      cellular metabolomes and interpret them in terms of metabolic changes taking
      place in a wide range of situations. The analytical methodology available is
      briefly presented and the applications developed so far are reviewed. These
      include differences in cell properties (e.g., drug resistance, cell cycle stage,
      specific growth conditions and genetic characteristics) and changes induced in
      response to different perturbations (e.g., disease, drug exposure and
      irradiation).

PMID- 21083107
TI  - Metabonomic studies of schizophrenia and psychotropic medications: focus on
      alterations in CNS energy homeostasis.
AB  - Schizophrenia is a severe neuropsychiatric disorder with a poorly understood
      etiology and progression. We and other research groups have found that energy
      metabolic pathways in the CNS are perturbed in many subjects with this disorder.
      Antipsychotic drugs that generally target neurotransmission are currently used
      for clinical management of the disorder, although these can also have marked
      effects on energy metabolism in the CNS and periphery. Recent proteomic and
      metabonomic studies have shown that molecular pathways associated with brain
      energy metabolism are altered in both the disorder and by antipsychotic
      treatments. This review focuses on discussion of these molecular alterations.
      Increased knowledge in this area could facilitate biomarker identification and
      drug discovery based on improving brain energy metabolism in this debilitating
      disorder.

PMID- 21083108
TI  - Database searching for structural identification of metabolites in complex
      biofluids for mass spectrometry-based metabonomics.
AB  - MS and HPLC are commonly used for compound characterization and obtaining
      structural information; in the field of metabonomics, these two analytical
      techniques are often combined to characterize unknown endogenous or exogenous
      metabolites present in complex biological samples. Since the structures of a
      majority of these metabolites are not actually identified, the result of most
      metabonomic studies is a list of m/z values and retention times. However, without
      knowing actual structures, the biological significance of these 'features' cannot
      be determined. The process of identifying the structures of unknown compounds can
      be time intensive, costly and frequently requires the use of multiple orthogonal
      analytical techniques - this laborious procedure seems insurmountable for the
      long lists of unknowns that must be identified for each study. In addition, the
      limited sample volume and the extremely low concentration of most endogenous
      analytes frequently make purification and identification by other instrumentation
      nearly impossible. This review is intended to explore the problems and progress
      with current tools that are available for MS-based structure identification for
      both endogenous and exogenous metabolites.

PMID- 21083109
TI  - Metabolomics for early detection of drug-induced kidney injury: review of the
      current status.
AB  - The identification of biomarkers of drug-induced kidney injury is an area of
      intensive focus in drug development. Traditional markers of renal function,
      including blood urea nitrogen and serum creatinine, are not region-specific and
      only increase significantly after substantial kidney injury. Therefore, more
      sensitive markers of kidney injury are needed. The ideal biomarkers will identify
      nephrotoxicity early in the drug-discovery process, resulting in decreased
      development costs and safer drugs. Metabolomics, the study of the small
      biochemicals present in a biological sample, has become a promising player in the
      nephrotoxicity arena. In this review, we describe the current status of the
      identification of metabolic biomarkers for drug-induced kidney toxicity
      screening. Many of these markers have been confirmed across multiple studies and
      can detect nephrotoxicity earlier than the traditional clinical chemistry and
      histopathology methods. Upon further validation, such markers will offer clear
      benefits for the pharmaceutical industry and regulatory agencies.

PMID- 21083110
TI  - Mass spectrometry-based technologies for high-throughput metabolomics.
AB  - The metabolome is composed of a vast number of small-molecule metabolites that
      exhibit a diversity of physical and chemical properties and exist over a wide
      dynamic range in biological samples. Multiple analytical techniques, used in a
      complementary manner, are required to achieve high coverage of the metabolome. MS
      is playing a central role in metabolomics research. Herein, we present a brief
      overview of the MS-based technologies employed for high-throughput metabolomics.
      These technologies range from chromatography-MS techniques, such as GC-MS and LC
      MS, to chromatography-free techniques, such as direct infusion, matrix-assisted
      and matrix-free laser desorption/ionization, imaging and some new ambient
      ionization approaches. Chemoinformatics and bioinformatics tools are widely
      available to facilitate successful metabolomics studies by turning the complex
      metabolomics data into biological information through streamlined data
      processing, analysis and interpretation.

PMID- 21083111
TI  - Supercritical fluids and green bioanalysis.

PMID- 21083112
TI  - Rapid peptide separation by supercritical fluid chromatography.
AB  - BACKGROUND: Supercritical fluid chromatography (SFC) is continually gaining
      attention in the separation sciences as demand increases for higher throughput
      isolations and purifications. The higher flow rates associated with SFC provide a
      significant decrease in analysis time and increase in sample-throughput
      efficiency. Peptides are of particular interest for SFC due, in part, to the
      rather extensive analysis time required by HPLC. RESULTS: This work explored a
      wide range of peptides not only for detection, but also for separation using SFC.
      A separation of five peptides ranging in molecular weights from 238.2 to 1046.2
      was achieved by SFC in less than 12 min, compared with 50 min using HPLC.
      CONCLUSION: This research further illustrates the ever-expanding applicability of
      SFC to a wider variety of compound classes. The rapid analysis time associated
      with SFC, as seen in this work, provides a nearly fivefold decrease in analysis
      time when compared with HPLC.

PMID- 21083113
TI  - Bioanalytical applications using supercritical fluid techniques.
AB  - The bioanalytical applications of supercritical fluid techniques, such as
      supercritical fluid extraction (SFE) and supercritical fluid chromatography
      (SFC), are of increasing interest. The main role of these techniques is in the
      sample preparation and separation of biologically active compounds, particularly
      drugs and their metabolites, as well as endogenous compounds. An insight is given
      into the different types of extracting fluids and modifiers, detectors,
      stationary phases, mobile phases and collection strategies. A critical discussion
      is presented on the existing state of the art concerning the applications of SFC
      and SFE with a specific focus on its advantages and limitations in the
      bioanalytical field. New developments and the possibilities for routine work in
      the near future are also covered.

PMID- 21083114
TI  - Metabolite analysis by supercritical fluid chromatography.
AB  - Owing to its favorable properties, such as low viscosity and high diffusivity, a
      supercritical fluid can be used as the mobile phase in chromatography.
      Supercritical fluid chromatography (SFC) can provide high-speed and high
      resolution separation. Since supercritical carbon dioxide (SCCO(2)), which is
      generally used as the mobile phase in SFC, is automatically emitted at room
      temperature, SFC is most commonly used as a preparative method. However, SFC can
      also be used to perform high-precision biomolecular analysis, especially for
      hydrophobic metabolites, because of the low polarity of SCCO(2). The use of a
      mass spectrometer with SFC can widen the scope of application of SFC to
      bioanalysis. In this review, we summarize practical application of SFC as a tool
      for the analysis of metabolites in real biological samples.

PMID- 21083115
TI  - The pharmaceutical industry and bioanalysis in India.

PMID- 21083117
TI  - Biopharmaceutical Emerging Best Practices Association 2009.
AB  - The Biopharmaceutical Emerging Best Practices Association is a not-for-profit
      association founded in 2008 with the aim of providing "an international forum for
      the presentation and discussion of scientific issues and problems encountered in
      the biopharmaceutical community ... to promote development of innovative
      approaches and solutions thus facilitating safer and faster biopharmaceutical
      product development."

PMID- 21083118
TI  - The European Federation of Clinical Chemistry and Laboratory Medicine.
AB  - Laboratory medicine is at the heart of modern health care and diagnosis and
      effective treatment of patients is impossible without high-quality bioanalytical
      services. The European Federation of Clinical Chemistry and Laboratory Medicine
      is a professional federation working to ensure high standards across the
      discipline in all European countries. This article describes our work in science,
      education and professional development.

PMID- 21083120
TI  - 2009 White Paper on recent issues in regulated bioanalysis from the 3rd
      Calibration and Validation Group Workshop.
AB  - The 3rd Calibration and Validation Group Workshop on Recent Issues in Regulated
      Bioanalysis was organized by the Calibration and Validation Group as a 1.5-day
      full immersion workshop for contract research organizations, pharmaceutical
      companies and regulatory agencies to discuss several 'hot' topics concerning
      bioanalytical issues and regulatory challenges. A consensus was reached among
      panelists and attendees on many points regarding method validation of small
      molecules.

PMID- 21083121
TI  - Stable-labeled analogues and reliable quantification of nonprotein biomarkers by
      LC-MS/MS.
AB  - BACKGROUND: The aim was to develop, and establish as suitable to begin assessment
      by full validation, a quantitative LC-MS/MS method for asparagine in human
      plasma. Therein, to utilize a stable-labeled analogue of asparagine to act as
      surrogate analyte, producing complete calibration curves and corresponding QC
      samples and another m/z distinct stable-labeled analogue to act as internal
      standard. RESULTS: From two candidates, the surrogate analyte was selected
      through statistical comparisons of concentration-response data and the resultant
      method employed protein precipitation and LC on an unmodified silica column with
      multiple reaction monitoring detection mode. The calibration range was 50-10,000
      ng/ml. CONCLUSION: This method was successfully proven to meet the accuracy and
      precision acceptance criteria of current bioanalytical method validation
      guidelines.

PMID- 21083122
TI  - Determination of tigecycline in human skin using a novel validated LC-MS/MS
      method.
AB  - BACKGROUND: To develop and validate a sensitive and novel bioanalytical method
      for measuring tigecycline concentrations in human skin using LC-MS/MS. RESULTS:
      The method utilizes addition of a stabilizing agent to the human skin or
      surrogate (human liver or rat skin), homogenization of human skin in a strong
      acidic-methanol extraction solvent, centrifugation of the skin suspension,
      filtration of the skin suspension supernatant, separation by LC (PolarisTM C18-A
      50 * 2.0 mm), and detection of tigecycline by MS/MS. Linearity was 50-20,000
      ng/g, using a sample size of 100 mg. The intra-and inter-day accuracy and
      precision of the assay met acceptance criteria. CONCLUSION: This method has been
      successfully applied to 17 incurred human skin samples from volunteers with
      surgical infections who received intravenous doses of tigecycline (100 mg initial
      loading dose and 50 mg every 12 h for at least 2 days). Tigecycline
      concentrations in these samples ranged from 185 to 2853 ng/g.

PMID- 21083123
TI  - Validated HPLC method for quantitative determination of talinolol in rat plasma
      and application to a preclinical pharmacokinetic study.
AB  - BACKGROUND: A simple HPLC-UV method with a high reproducibility and sensitivity
      for the determination of talinolol in rat plasma was developed in this study.
      METHOD: After liquid-liquid extraction, the compounds were separated on a
      Vydac((r)) C18 monomeric column (250 * 4.6 mm inner diameter * 5-um particle
      size) using a mobile phase composed of acetonitrile and potassium dihydrogen
      phosphate buffer (34:66 v/v), delivered isocratically at a flow rate of 1.0 ml
      min(-1). Escitalopram was used as an internal standard. The chromatographic peak
      area ratio, based on UV absorbency at 245 nm, was used for quantitative analysis.
      RESULTS: Calibration standards with concentrations over the range of 10-1000 ng
      ml(-1) were validated for routine sample analysis to support pharmacokinetic
      studies with talinolol in rats. The intra- and inter-day precision studies showed
      good reproducibility with coefficients of variation of less than 11.49%. The
      developed method is simpler and more sensitive than previously reported methods.
      DISCUSSION: The analytical sensitivity and accuracy of this assay were adequate
      for characterization of talinolol in rat plasma and the assay has been applied
      successfully to the in vivo kinetic study of talinolol in rats. After talinolol
      (10 mg kg(-1)) was given orally, the maximum concentration and the AUC(0
      infinity) were 341.8 +/- 99.4 ng ml(-1) and 976.26 +/- 173.37 ng h ml(-1),
      respectively. The oral bioavailability was approximately 52.14 +/- 9.26%.
      CONCLUSION: The advantages of our method are a small sample volume (200 ul),
      short analysis time (13.5 min) and a simple sample extraction and clean-up
      compared with multiple extraction and washing steps and a longer analysis time in
      previously published methods.

PMID- 21083124
TI  - Guidelines for bioanalytical 2D chromatography method development and
      implementation.
AB  - 2D chromatography is a rapidly evolving, very powerful tool for bioanalysis.
      Advances in the theory of 2D separations, instrument technology and data analysis
      strategies continue to complement each other and advance the state of the art.
      Separations of complex mixtures of biomolecules yielding several hundred peaks in
      practical analysis times (tens of minutes to several hours) are relatively
      common. However, this level of performance largely remains the domain of expert
      researchers and several practical limitations stand in the way of more widespread
      use of 2D separations among practitioners. While off-the-shelf instruments are
      increasing in number, the most effective 2D instruments are often home-built, and
      analysis of the extremely rich datasets resulting from these separations
      continues to be a serious bottleneck in the overall workflow. This review
      summarizes some of the most serious challenges in method development and
      describes best practices to help guide users in designing effective 2D
      separations for bioanalysis.

PMID- 21083125
TI  - Headspace microextraction: recent bioanalytical applications and issues.
AB  - Headspace microextraction has already been established as the method of choice
      for analyzing volatiles blended in complex matrices, such as environmental, food
      and biological samples. The modern trend of analytical chemistry for 'going
      small' has led to the successful development of various sorbing materials and
      microextraction techniques. As it is anticipated, microextraction is usually
      combined with powerful separation and optical techniques permitting enhanced
      recoveries of analytes, selectivity and sensitivity. In addition, derivatization
      reactions are often employed for improved detectability of several classes of
      compounds. Volatile compounds of biological significance are key substances due
      to the fact that they may constitute a characteristic of the status of the
      organism. A closer look at the biological applications of the headspace
      microextraction techniques (solid-phase and single drop microextraction) is the
      primary aim of this review. The variability of biological samples and analytes
      are considered primarily, while derivatization and optimization strategies are
      also discussed.

PMID- 21083127
TI  - Why I love metabolites in safety testing (MIST): a light-hearted historical
      perspective.

PMID- 21083128
TI  - Microextraction by packed sorbent in bioanalysis.

PMID- 21083130
TI  - Young Investigator: Anderson Rodrigo Moraes de Oliveira.

PMID- 21083131
TI  - Challenges in developing antidrug antibody screening assays.
AB  - Robert Dodge is the Laboratory Director for Immunochemistry and Cell Biology at
      Taylor Technology, a Pharmanet company in Princeton, NJ, USA. Taylor Technology
      is a contract research laboratory specializing in assay development and sample
      testing in a good laboratory practice environment. Robert oversees a staff of
      scientists responsible for the development of assays for use in protein drug
      quantitation, antidrug antibody screening and biomarker detection. Protein drugs
      may elicit an immune response in the form of production of antidrug antibodies
      (ADAs) by a subject. This ADA response may have serious safety implications for
      subjects or, at a minimum, may affect drug efficacy. Bioanalytical testing for
      antidrug antibodies has therefore become a required part of safety testing for
      subjects receiving protein drugs. Regulatory guidance and scientific white papers
      recommend a tiered approach for bioanalytical ADA testing. The first assay in the
      tiered testing scheme is a screening assay, which tests all subjects in the study
      for the presence of ADAs. The screening assay is quasiquantitative, typically
      lacks a specific positive control and must be designed to detect numerous
      isotypes and subclasses of antibodies. These characteristics of an ADA screening
      assay differ from a those of a standard immunoassay designed to quantitate a
      specific protein in matrix and thus present unique challenges. This article
      reviews the unique challenges encountered during the development of an ADA assay.

PMID- 21083132
TI  - Incurred sample reanalysis: enhancing the Bland-Altman approach with tolerance
      intervals.
AB  - This article describes the need for incurred sample reanalysis and suggests that
      the combination of a Bland-Altman plot and tolerance intervals can provide a
      visual evaluation of method performance. It also shows how the proposed
      combination is a tool that may be of value in determining minimum sample size. An
      example dataset is worked through in its entirety so that a reader unfamiliar
      with the topic can gain sufficient information to analyze their own data. Related
      topics include the generation of 66.7% tolerance factors, comparison of mean
      normalized and log differences and the use of probability plots to evaluate error
      distributions. The suggestions presented in this article are meant to be a
      continuation of the ongoing incurred sample reanalysis discussion and, as such,
      further comment is invited.

PMID- 21083133
TI  - High-throughput salting-out assisted liquid/liquid extraction and ultrafast LC
      for same-day delivery of first-in-human bioanalytical data.
AB  - BACKGROUND: With the need of fast-paced drug development, rapid delivery of
      bioanalytical data becomes a trend. Here, we present a strategy to demonstrate
      same-day data delivery. RESULTS: A novel salting-out assisted liquid/liquid
      extraction (SALLE) with acetonitrile and a MS-friendly salt was used to extract
      analyte from the first-in-human study plasma samples and the extract was
      successfully injected into ultrafast chromatography. The strategic combination of
      SALLE and ultrafast chromatography minimizes the turnaround time and allows the
      same-day delivery of bioanalytical data. The time saving from both extraction and
      injection was translated to a fast delivery of bioanalytical data. CONCLUSION:
      The first-in-human pharmacokinetic data of an investigational new drug candidate
      was delivered in approximately 4.5 work h after receiving the samples of each
      dose group using high-throughput SALLE and ultrafast LC. Incurred sample reassay
      results proved uncompromised data quality with the high-speed bioanalysis.

PMID- 21083134
TI  - Use of magnetic beads to study the interaction of ristocetin with peptides and
      bacteria.
AB  - BACKGROUND: We aimed to develop and validate sensitive fluorescence techniques to
      assess the binding of magnetic microbeads derivatized with ristocetin from
      Amycolatopsis lurida to carboxyfluorescein-labeled D-Ala-D-Ala-D-Ala and in
      competition with Staphylococcus aureus bacteria. Glycopeptide antibiotics have
      been widely used to treat bacterial infections. However, new antibiotics are
      needed because of growing bacterial resistance and serious side effects. To
      screen potential candidates for new antibiotics, there is a great demand for
      sensitive, fast and inexpensive techniques to analyze the interactions between
      these molecules and bacterial cells. RESULTS: Fluorometry, an in-house
      fluorescent instrument and fluorescence microscopy were used to determine binding
      constants of 2.75 * 10(4), 2.21 * 10(4) and 0.81 * 10(4) M(-1), respectively, for
      the interaction between ristocetin and the labeled peptide. CONCLUSION: The
      methods detailed herein have been successfully applied to assess the binding of
      carboxyfluorescein- labeled D-Ala-D-Ala-D-Ala to ristocetin on microspheres. The
      magnetic bead-based immunoassay could be used to detect bacteria at low
      concentrations.

PMID- 21083135
TI  - Assessment of nerve agent exposure: existing and emerging methods.
AB  - The perceived threat of the use of nerve agents by terrorists against civilian
      targets implies the need for methods for point-of-care (POC) diagnosis. This
      review presents an overview of methods that are currently available for the
      assessment of exposure to nerve agents. Since these methods are mostly MS based,
      they require complex and expensive equipment and well-trained personnel and,
      consequently, they are not very suitable for rapid POC diagnosis. However, new
      technologies are emerging that allow, among others, immunochemical detection of
      acetylcholinesterase inhibited by nerve agents. Also, lab-on-a-chip methodologies
      are under development. It is anticipated that MS methods will be suitable for POC
      diagnosis within a few years, due to the miniaturization of equipment and the
      emergence of methodologies that enable mass spectrometric analysis with little
      sample pretreatment and that are potentially fieldable, such as direct analysis
      in real time and desorption electrospray ionization MS.

PMID- 21083136
TI  - Advances in bioanalytical LC-MS using the OrbitrapTM mass analyzer.
AB  - The continuing desire to analyze complex biological samples with the minimum
      number of steps places high demands on increasing speed, dynamic signal range,
      quantitative capability and the facility with which the mass spectrometers can
      interface with chromatographic separation methods. Reliable identification of
      metabolites in complex mixtures requires robust mass spectrometers with high
      resolving power, mass accuracy, sensitivity and dynamic range, while tandem MS is
      an invaluable tool for further structural characterization. This review begins
      with a discussion of the key properties of the OrbitrapTM mass analyzer: mass
      accuracy, resolution, fidelity of isotope pattern abundancies and dynamic range.
      The main objective is to provide an overview of Orbitrap applications in the
      field of bioanalysis. Specific areas of drug metabolism, doping control and food
      contaminants are discussed in detail illustrating the performance and versatility
      of the Orbitrap mass analyzer.

PMID- 21083137
TI  - Benzodiazepines: sample preparation and HPLC methods for their determination in
      biological samples.
AB  - Benzodiazepines (BDZs) belong to a group of substances known for their sedative,
      antidepressive, muscle relaxant, tranquilizer, hypnotic and anticonvulsant
      properties. Their determination in biological fluids is essential in clinical
      assays as well as in forensics and toxicological studies. Researchers focus on
      the development of rapid, accurate, precise and sensitive methods for the
      determination of BDZs and their metabolites. A large number of analytical methods
      using different techniques have been reported, but none can be considered as the
      method of choice. BDZs are usually present at trace levels (microgram or nanogram
      per milliliter) in a complex biological matrix and the potentially interfering
      compounds must be isolated by various extraction techniques before analysis. An
      extended and comprehensive review is presented herein, focusing on sample
      preparation (pretreatment and extraction) and HPLC conditions applied by
      different authors. These methods enable bioanalysts to achieve detection limits
      down to 1-2 ng/ml using UV/diode array detection, readily available in most
      laboratories, and better than 1 ng/ml using electron capture detection, which is
      lower than that obtained using a nitrogen phosphorus detector. MS interfaced with
      electrospray ionization offered a similar sensitivity, while negative chemical
      ionization MS or sonic spray ionization MS provided sensitivity down to 0.1
      ng/ml.

PMID- 21083138
TI  - Modern techniques for the determination of anabolic-androgenic steroid doping in
      the horse.
AB  - Control of the use of performance-affecting substances in the horse is critical
      to the integrity of a wide range of equine sports, with major implications for
      both animal welfare and revenue streams. One class of medications enjoying
      particular public notoriety is the anabolic-androgenic steroid group, as
      highlighted by the recent 'Big Brown' affair and Congressional inquiries into the
      use of steroids in professional sports, including horse racing, in the USA. This
      review examines the latest developments pertaining to the analytical detection of
      these substances in equine biological samples and the supporting regulatory
      environment. Consideration is given to the full variety of sample matrices
      available, together with modern sample preparative approaches and instrumental
      techniques. Issues concerning the regulation of endogenous steroids, including
      thresholds where applicable, are also discussed.

PMID- 21083139
TI  - Challenges in applying chemometrics to LC-MS-based global metabolite profile
      data.
AB  - Metabolite profiling can provide insights into the metabolic status of complex
      living systems through the non-targeted analysis of metabolites in any biological
      sample. Metabolite profiling is complementary to genomics, transcriptomics and
      proteomics, and its applications span epidemiology, disease diagnosis, nutrition,
      pharmaceutical research, and toxicology. Metabolic phenotypes are a reflection of
      an organism's environment, lifestyle, diet, gut microfloral composition and are
      also influenced by genetic factors, with important implications in genome-wide
      association studies. Specialized analytical platforms, such as NMR spectroscopy
      and MS, are required to interrogate such metabolic complexity. The increased
      sophistication of such techniques has lead to a demand for improved data analysis
      approaches, including preprocessing and advanced chemometric techniques. This
      article discusses data generation, preprocessing, multivariate analysis and data
      interpretation for LC-MS-based metabolite profiling, focusing on challenges
      encountered and potential solutions.

PMID- 21083140
TI  - Biotechnological synthesis of drug metabolites using human cytochrome P450
      isozymes heterologously expressed in fission yeast.
AB  - Cytochrome P450 mono-oxygenases (CYPs) are the major enzymes involved in the
      metabolism of drugs and poisons in humans. The variation of their activity - due
      to genetic polymorphisms or enzyme inhibition/induction - potentially increases
      the risk of side effects or toxicity. Studies on CYP-dependent metabolism are
      important in drug-development or toxicity studies. Reference standards of drug
      metabolites required for such studies, especially in the context of metabolites
      in safety testing (MIST), are often not commercially available and their
      classical chemical synthesis can be cumbersome. Recently, a biotechnological
      approach using human CYP isozymes heterologously expressed in fission yeast was
      developed for the synthesis of drug metabolites. Among other aspects, this
      approach has the distinct advantages that the reactions run under mild conditions
      and that only the final product must be isolated and characterized. This review
      overviews the first practical applications of this new approach and discusses the
      selection of substrates, metabolites and fission yeast strains as well as
      important aspects of incubation, product isolation and clean-up.

PMID- 21083141
TI  - Metabolite quantitation: detector technology and MIST implications.
AB  - HPLC detector technology has advanced dramatically over the past 20 years, with a
      range of highly sensitive and specific detectors becoming available. What is
      still missing from the bioanalyst's armoury, however, is a highly sensitive
      detector that gives an equimolar response independent of the compound. This would
      allow for quantification of compounds without the requirement for a synthetic
      standard or a radiolabeled analogue. In particular, such a detector applied to
      metabolism studies would establish the relative significance of the various
      metabolic routes. The recently issued US FDA guidelines on metabolites in safety
      testing (MIST) focus on the relative quantitation of human metabolites being
      obtained as soon as feasible in the drug-development process. In this article,
      current detector technology is reviewed with respect to its potential for
      quantitation without authentic standards or a radiolabel and put in the context
      of the MIST guidelines. The potential for future developments are explored.

PMID- 21083142
TI  - Recent progress in selected reaction monitoring MS-driven plasma protein
      biomarker analysis.
AB  - The plasma proteome offers a wealth of opportunity to develop protein-based
      assays for diagnostic, prognostic and predictive biomarkers. Nonetheless, the
      unique properties of plasma, with its high dynamic range of protein
      concentrations and the vast complexity of protein species, present considerable
      analytical challenges. The continuing maturation of proteomic technologies, in
      particular biological MS instrumentation and immunoaffinity sample preparation
      strategies, is driving progress in the field. Selected reaction monitoring (SRM)
      MS of peptides derived from plasma proteins is one such development that
      facilitates high-fidelity selection and quantitation with only minimal prior
      sample enrichment, while coupling targeted immunoaffinity enrichment prior to SRM
      MS further enhances detection of less-abundant plasma proteins present in the
      subnanogram per millilitre concentration. This article reviews recent progress in
      the bioanalysis of plasma proteins driven by SRM-MS.

PMID- 21083144
TI  - Bioanalysis going global.

PMID- 21083145
TI  - Therapeutic drug monitoring in oncology: does it have a future?

PMID- 21083147
TI  - Society spotlight: Spotlight on the calibration and validation group.
AB  - The Calibration and Validation Group (CVG) was founded in early 1995 by Herman
      Lam, Chung Chow Chan and YC Lee in Toronto, Canada. At that time, the
      requirements and the practices of method validation, analytical system
      qualification and instrument performance verification were only discussed
      individually among a very small group of professionals; the founders realized
      that there was a need to form a scientific organization to focus on those
      subjects and share the learning. Initially, the membership was mainly derived
      from the regulated pharmaceutical industry, but the participation has grown over
      the years to include scientists from a wide range of backgrounds, including
      pharmaceuticals, chemicals, environmental, food, distilleries, biotechnology,
      instrument vendors, government agencies, local colleges and universities. CVG was
      officially incorporated as a nonprofit organization in Canada in 1999.

PMID- 21083148
TI  - Young investigator: Stephen William Holman.

PMID- 21083149
TI  - Ion suppression and cannulation locking solutions.
AB  - Ion suppression is a common concern when utilizing liquid chromatography-tandem
      mass spectrometry for quantitation of analytes in biological samples. Ion
      suppression can cause the analytical signal for the analyte and/or the internal
      standard to be reduced compared with prepared analytical standards, leading to
      erroneous quantitation values for the desired analyte of interest. While it has
      become commonplace to note ion suppression due to the dosing vehicle in in vivo
      experiments, we have observed a similar phenomenon of ion suppression due to the
      components of the locking solution used to keep the cannula patent in certain
      rodent experiments. During one such typical bioanalysis of a drug candidate dosed
      to a cannulated rodent, significant ion suppression (~60%) was observed for the
      structural analogue internal standard, which led to this investigation that
      revealed the cannula locking solution as the source of the ion suppression.

PMID- 21083150
TI  - Automated liquid-liquid extraction method for high-throughput analysis of
      rosuvastatin in human EDTA K2 plasma by LC-MS/MS.
AB  - BACKGROUND: Liquid-liquid extraction has been widely used for the analysis of
      rosuvastatin due to its many attractive features, such as low cost and clean
      extract. However, manual transfer of the organic phase poses a challenge,
      particularly when a batch size is large. To overcome the challenge, a simple
      automated high-throughput (192 samples per batch) liquid-liquid extraction method
      with short (3.0-min) chromatographic run time was proposed. Rosuvastatin was
      separated using a gradient on a reversed-phase C18 column and detected in the
      multiple reaction monitoring made with a mass transition of m/z 482.3->258.2 amu.
      RESULTS: The assay exhibited a linear range from 50 to 25000 pg/ml (r >= 0.9976).
      The intra- and inter-day accuracy ranged from 98.16 to 103.84% and 101.18 to
      103.95%, respectively. The intra- and inter-day precision ranged from 0.70 to
      6.17% and 2.19 to 5.07%, respectively. CONCLUSION: Finally, the validated method
      was successfully applied to bioequivalence studies.

PMID- 21083151
TI  - Impact of plasma and whole-blood anticoagulant counter ion choice on drug
      stability and matrix effects during bioanalysis.
AB  - BACKGROUND: Anticoagulants are used to prevent coagulation in blood samples. The
      plasma pH may change with a different counter ion and anticoagulant; thus, it is
      essential to determine effects on drug stability and the matrix effect during the
      bioanalytical method development. RESULTS: Cross-validation of multiple compounds
      between different counter ions was performed and no impact from the counter ion
      nature was demonstrated. Moreover, plasma stabilities and matrix effects for both
      fluconazole and granisetron were investigated thoroughly in numerous counter
      ions/anticoagulants (K(3)ethylenediaminetetraacetic acid [K(3)EDTA], K(2)EDTA,
      NaEDTA, NaHeparin and LiHeparin). Sirolimus, a large cyclic molecule, was also
      tested in different whole-blood EDTA counter ions. Results showed percentage
      deviation less than 8.5% and percentage cross-validation less than 8.4%.
      CONCLUSION: None of the compounds tested had an impact on the matrix stabilities
      and matrix effect.

PMID- 21083152
TI  - LC-SPE-NMR-MS: a total analysis system for bioanalysis.
AB  - Liquid chromatography (LC)-solid-phase extraction (SPE)-nuclear magnetic
      resonance (NMR)-mass spectrometry (MS) coupling is a key technology for fast and
      thorough structure elucidation of valuable mass-limited samples. Laborious serial
      isolation and purification procedures of metabolites, byproducts or impurities
      from complex biomatrices, natural product extracts or other mixtures of several
      components can be circumvented by the use of this integrated modular system. This
      combination of high-end analytical technology significantly accelerates the
      structure-elucidation process for valuable samples present in minute quantities
      in mixtures. The information depth is significantly increased by the concurrent
      availability of NMR and MS data of one chromatographic peak. Thus, this flexible
      technique is well on its way to becoming the gold standard in analytical
      chemistry of mixtures. LC-SPE-NMR-MS overcomes the limitations of directly
      coupled LC-NMR. Full flexibility regarding chromatographic conditions and NMR
      acquisition is gained by this modular technique. LC-SPE-NMR-MS allows for a rapid
      structure-elucidation process that would not be possible on the basis of MS or
      NMR data alone.

PMID- 21083153
TI  - Enantioselective quantification of chiral drugs in human plasma with LC-MS/MS.
AB  - Today, approximately 60% of synthetic drugs are chiral and 88% of these chiral
      synthetic drugs are used therapeutically as racemates. However, for many racemic
      drugs, their stereospecific plasma pharmacokinetics in humans are not known due
      to the limitations of the analytical methods. Nowadays, liquid chromatography
      (LC)-tandem mass spectrometry (MS/MS) methods based on various chiral stationary
      phases (CSPs), with a high degree of specificity and sensitivity, have been
      widely used in enantioselective determination of chiral drugs and/or their
      metabolites in human plasma. The technologies and issues when coupling chiral
      chromatography with MS/MS detection in bioanalytical methods will be reviewed
      herein. The introduction and applications of various CPSs, including
      polysaccharide-, macrocyclic glycopeptide-, protein- and cyclodextrin-based
      phases, are described here. This review also includes a discussion of interface
      and matrix effects in enantioselective LC-MS/MS methods.

PMID- 21083154
TI  - Restricted-access media supports for direct high-throughput analysis of
      biological fluid samples: review of recent applications.
AB  - This review presents an update on the use of restricted-access materials (RAMs)
      for direct injection of biological samples. The fundamental improvements in the
      preparation of tailored RAMs and the diversity of applications with these phases
      are presented. Insights into diminishing the matrix effect by the use of RAM
      supports in methods by LC-MS and into the low number of methods for enantiomeric
      separations by direct injections of biological samples are addressed. The
      diversity of systems that incorporate RAMs for selective sample clean-up or
      fractionation in proteome and peptidome analysis is also covered.

PMID- 21083155
TI  - Bioanalysis of siRNA and oligonucleotide therapeutics in biological fluids and
      tissues.
AB  - This article summarizes bioanalytical avenues for the determination of siRNA and
      oligonucleotide therapeutics, with an emphasis on hybridization methods. Aspects
      of the chemistry and delivery of investigational oligonucleotide therapeutics are
      considered. The nature of the oligonucleotide under investigation will dictate
      the best analytical course of action; each method has its advantages and
      disadvantages, depending upon the oligonucleotide test article and the
      anticipated toxicokinetic and pharmacokinetic study parameters. Stringent method
      development and specific validation criteria are essential to attain the best
      quality results in support of a regulatory filing.

PMID- 21083156
TI  - Assessing specificity for immunogenicity assays.
AB  - Developing sensitive and specific bioanalytical assays for measuring the
      immunogenicity of biological therapeutics has become an integral component of the
      drug-development process. The strategy for measuring these immune responses
      involves performing sensitive screening assays that are capable of detecting low
      levels of both low- and high-affinity antibodies. However, having sensitive
      assays inherently results in a certain rate of false-positivity. Hence,
      developing steps to determine specificity in these assays is important to confirm
      the presence of antidrug antibodies. The specificity assays are defined by the
      ability of an assay to score a positive result if the serum sample contains an
      antibody that can bind and/or neutralize the therapeutic protein. Here, we
      discuss the methodologies for determining specificity in the bioanalytical assays
      used for measuring antidrug antibodies. These methods will provide investigators
      and regulators with guidelines to develop and review assays to measure antidrug
      antibodies, which can specifically interfere with the actions of the drug and/or
      influence the safety profile of the therapeutic proteins.

PMID- 21083157
TI  - Torcetrapib for animal and human pharmacokinetic studies: applicability of chiral
      and achiral methodologies.
AB  - The emergence of bioanalysis as a key tool in the drug-discovery and -development
      process has enabled the development of sensitive, precise and specific
      bioanalytical methods in recent years. These methods have enabled the progress of
      novel chemical entities through the life cycle of drug discovery and development.
      The focus of this review article is on a well-known cholesteryl ester transfer
      protein (CETP) inhibitor known as torcetrapib. Although torcetrapib was withdrawn
      from clinical development, it is important to understand the various
      bioanalytical methodologies (chiral and achiral) that are readily available for
      the pharmacokinetic/pharmacodynamic characterization of the drug. Additionally,
      these methodologies may be applicable to the bioanalysis of the next-generation
      CETP inhibitors. This review covers the development and validation of assay
      methods that were used to obtain preclinical and clinical pharmacokinetic
      parameters of torcetrapib. Accordingly, methods are available for the
      determination of torcetrapib in various species, namely dogs, hamsters, rats,
      mice, monkeys and humans. Since torcetrapib is a chiral compound, methods have
      been developed for stereoselective bioanalysis to evaluate in vivo chiral
      inversion phenomena. Interestingly, torcetrapib can be analyzed by various
      bioanalytical options (e.g., HPLC-UV, LC-MS, LC-MS/MS and GC-MS assays) depending
      on the type of species under consideration with the associated sensitivity
      requirements. This review covers all the available methodologies for torcetrapib,
      providing both assay-development and -optimization strategies. It also tabulates
      validation parameters and enumerates the difficulties, challenges and nuances of
      the various published assays for torcetrapib.

PMID- 21083158
TI  - Ligand-binding assays: risk of using a platform supported by a single vendor.
AB  - The use of biological reagents in ligand-binding assays (LBAs) presents inherent
      challenges when measuring the concentration of large molecules in complex
      matrices. As a result, there are relatively few platforms that provide the
      accuracy, precision and robustness needed to determine the concentration of
      macromolecular therapies and biomarkers, and demonstrate the presence or absence
      of an immune response. Some bioanalytical laboratories use only one LBA platform
      to reduce costs, increase efficiency and maintain optimal assay performance.
      However, the business and regulatory risks of using a single platform supported
      by only one vendor should be considered. This article summarizes the
      immunological methods used to support bioanalysis for large molecules that are
      supported by a single vendor, the benefits of being dedicated to a single
      platform for bioanalysis used for regulatory filings, the costs associated with
      restructuring if an immunoassay platform is discontinued and recommendations to
      mitigate risk when using LBAs in drug development. The experience with the recent
      discontinuation of the BioVerisTM electrochemiluminescent-based platform is
      discussed.

PMID- 21083159
TI  - Current technologies and considerations for drug bioanalysis in oral fluid.
AB  - Drug oral fluid analysis was first used almost 30 years ago for the purpose of
      therapeutic drug monitoring. Since then, oral fluid bioanalysis has become more
      popular, mainly in the fields of pharmacokinetics, workplace drug testing,
      criminal justice, driving under the influence testing and therapeutic drug
      monitoring. In fact, oral fluid can provide a readily available and noninvasive
      medium, without any privacy loss by the examinee, which occurs, for instance,
      during the collection of urine samples. It is believed that drug concentrations
      in oral fluid may parallel those measured in blood. This feature makes oral fluid
      an alternative analytical specimen to blood, which assumes particular importance
      in roadside testing, the most published application of this sample. Great
      improvements in the development of accurate and reliable methods for sample
      collection, in situ detection devices (on-site drug detection kits), and highly
      sensitive and specific analytical methods for oral fluid testing of drugs have
      been observed in the last few years. However, without mass spectrometry-based
      analytical methods, such as liquid chromatography coupled to mass spectrometry
      (LC-MS) or tandem mass spectrometry (LC-MS/MS), the desired sensitivity would not
      be met, due to the low amounts of sample usually available for analysis. This
      review will discuss a series of published papers on the applicability of oral
      fluid in the field of analytical, clinical and forensic toxicology, with a
      special focus on its advantages and drawbacks over the normally used biological
      specimens and the main technological advances over the last decade, which have
      made oral fluid analysis of drugs possible.

PMID- 21083161
TI  - First-in-human assays: excitement and introspection.

PMID- 21083162
TI  - Hybrid immunoaffinity--mass spectrometric methods for efficient protein biomarker
      verification in pharmaceutical development.

PMID- 21083164
TI  - Conference report: European Bioanalysis Forum.

PMID- 21083165
TI  - Young investigator: Aaron Hernandez-Santana.

PMID- 21083166
TI  - Dublin City University Bioanalytical Chemistry and Diagnostics Group.

PMID- 21083168
TI  - Quantification of 4-methylaminoantipyrine, the active metabolite of dipyrone, in
      human plasma.
AB  - BACKGROUND: Dipyrone (metamizole) is a nonsteroidal anti-inflammatory drug used
      as an analgesic and antipyretic in both pediatric and adult patients. Dipyrone
      hydrolyses to 4-methylaminoantipyrine (MAA) in the stomach before absorption.
      There are several HPLC methods available for analysis of MAA from human plasma
      but no method has yet been developed on liquid chromatography-mass spectrometry
      (LC-MS) or LC tandem MS (LC-MS/MS), which are much more specific and sensitive
      techniques. METHODOLOGY: A high-performance LC-MS method for the quantification
      of 4-methylaminoantipyrine from human plasma has been developed, validated and
      applied to a pharmacokinetic study of 500 mg oral dose dipyrone. Following liquid
      liquid extraction, the analyte was first separated on a reverse phase column
      using isocratic mobile phase and then analyzed by MS in selected ion monitoring
      mode using [M+H](+) ions, m/z 218.2 for 4-methylaminoantipyrine and 231.3 for 4
      isopropylantipyrine (internal standard). RESULTS: The method exhibited a linear
      range from 0.2 to 10.0 ug/ml when only 100 ul human plasma sample was used. The
      lower limit of detection was 0.04 ug/ml (160 pg on column). The recovery was 80%.
      The accuracy and precision were obtained over the calibration curve range and
      were well within the limits specified under guidelines for bioanalytical method
      validation. The compound was stable under the experimental conditions.
      CONCLUSION: The method was demonstrated to be, simple, sensitive and rapid. It
      can be easily adopted in laboratories with access to LC-MS or MS/MS and applied
      to sample analysis in clinical settings where a large number of samples are
      generated.

PMID- 21083167
TI  - From research to regulated: challenges in transferring methods.
AB  - The current decade has seen an evolution in biomarker research, with a
      breakthrough from traditional single analyte studies to simultaneous multiple
      analyte technologies, aided by the progressive development of research tools and
      the discovery of many novel biomarkers. It is foreseeable that the application of
      such technologies will have an integral role in clinical studies for establishing
      biomarker profiles of disease status and prognosis. However, the transfer of such
      complex procedures to a regulated environment presents many obstacles. Here, we
      discuss some of these applied technologies and the validation approaches we have
      taken as an academic unit to prove their suitability and appropriateness for
      clinical application. We discuss the advantages and limitations for such end
      point assays in early Phase clinical trials.

PMID- 21083169
TI  - MALDI-tandem mass spectrometry imaging of astemizole and its primary metabolite
      in rat brain sections.
AB  - BACKGROUND: Matrix-assisted laser desorption/ionization (MALDI)-tandem mass
      spectrometry (MS)/MS is a proven reliable tool for visualizing the spatial
      distribution of dosed drugs and their primary metabolites in animal tissue
      sections. MATERIALS & METHODS: The rat brain tissue sections coated with
      dihydroxybenzoic acid as matrix, were analyzed by MALDI-MS/MS imaging
      experiments. The potential metabolites of astemizole in rat brain homogenate
      selected for MALDI-MS/MS imaging experiments were first identified by high
      performance liquid chromatography coupled to an electrospray ionization source
      and a hybrid-quadrupole-linear-ion-trap mass spectrometer. RESULTS: Astemizole
      was observed to be heterogeneously distributed to most parts of the brain tissue
      slices including the cortex, hippocampus, hypothalamic, thalamus and ventricle
      regions, while its major metabolite, desmethylastemizole, was only found around
      ventricle sites. CONCLUSION: The results indicated that the dosed compound alone
      might be responsible for the CNS side-effects when drug exposures became
      elevated.

PMID- 21083170
TI  - Imaging mass spectrometry for the assessment of drugs and metabolites in tissue.
AB  - The study of drug distribution within biological tissue is a key part of the
      development of new pharmaceuticals. Matrix-assisted laser desorption ionization
      mass spectrometric imaging is a powerful new imaging technique that can be used
      to study the distribution of a diverse range of endogenous and xenobiotic
      compounds within biological tissue. Here, fundamental aspects of the technique,
      appropriate instrumentation and applications in the study of xenobiotics and
      metabolite distribution are described. Sample preparation issues and some of the
      challenges in data interpretation/handling are also discussed.

PMID- 21083171
TI  - Biomarkers and imaging: physics and chemistry for noninvasive analyses.
AB  - The era of 'modern medicine' has changed its name to 'molecular medicine', and
      reflects a new age based on personalized medicine utilizing molecular biomarkers
      in the diagnosis, staging and monitoring of therapy. Alzheimer's disease has a
      classical biomarker determined at autopsy with the histologic staining of amyloid
      accumulation in the brain. Today we can diagnose Alzheimer's disease using the
      same classical pathologic biomarker, but now using a noninvasive imaging probe to
      image the amyloid deposition in a patient and potentially provide treatment
      strategies and measure their effectiveness. Molecular medicine is the
      exploitation of biomarkers to detect disease before overt expression of
      pathology. Physicians can now find, fight and follow disease using imaging, and
      the need for other disease biomarkers is in high demand. This review will discuss
      the innovative physical and molecular biomarker probes now being developed for
      imaging systems and we will introduce the concepts needed for validation and
      regulatory acceptance of surrogate biomarkers in the detection and treatment of
      disease.

PMID- 21083172
TI  - New ultrasensitive detection technologies and techniques for use in microdosing
      studies.
AB  - In a microdosing study, subpharmacologically active doses of drug are given to
      human volunteers at an early stage of development in order to obtain preliminary
      pharmacokinetic data. The very low doses of drug administered (<=100 ug)
      consequently lead to very low concentrations of drug appearing in the body and
      therefore highly sensitive analytical techniques are required. There are three
      such analytical technologies currently used in microdosing studies: PET, liquid
      chromatography (LC)-tandem mass spectrometry (MS/MS) and accelerator mass
      spectrometry (AMS). Both PET and AMS employ radioisotopic tracers. PET is an
      imaging technique and AMS is an extremely sensitive isotope ratio method, able to
      measure drug concentrations in the ag/ml range. LC-MS/MS does not require the
      presence of an isotopic tracer and its sensitivity is in the pg/ml range. This
      review examines each of these three analytical modalities in the context of
      performing microdosing studies.

PMID- 21083173
TI  - Accelerating analysis for metabolomics, drugs and their metabolites in biological
      samples using multidimensional gas chromatography.
AB  - Gas chromatography (GC) with mass spectrometry (MS) is one of the great enabling
      analytical tools available to the chemical and biochemical analyst for the
      measurement of volatile and semi-volatile compounds. From the analysis result, it
      is possible to assess progress in chemical reactions, to monitor environmental
      pollutants in a wide range of soil, water or air samples, to determine if an
      athlete or horse trainer has contravened doping laws, or if crude oil has
      migrated through subsurface rock to a reservoir. Each of these scenarios and
      samples has an associated implementation method for GC-MS. However, few samples
      and the associated interpretation of data is as complex or important as
      biochemical sample analysis for trace drugs or metabolites. Improving the
      analysis in both the GC and MS domains is a continual search for better
      separation, selectivity and sensitivity. Multidimensional methods are playing
      important roles in providing quality data to address the needs of analysts.

PMID- 21083174
TI  - From known knowns to known unknowns: predicting in vivo drug metabolites.
AB  - 'It is better to be useful than perfect'. This review attempts to critically
      cover and assess the currently available approaches and tools to answer the
      crucial question: Is it possible (and if it is, to what extent is it possible) to
      predict in vivo metabolites and their abundances on the basis of in vitro and
      preclinical animal studies? In preclinical drug development, it is possible to
      produce metabolite patterns from a candidate drug by virtual means (i.e., in
      silico models), but these are not yet validated. However, they may be useful to
      cover the potential range of metabolites. In vitro metabolite patterns and
      apparent relative abundances are produced by various in vitro systems employing
      tissue preparations (mainly liver) and in most cases using liquid chromatography
      mass spectrometry analytical techniques for tentative identification. The pattern
      of the metabolites produced depends on the enzyme source; the most comprehensive
      source of drug-metabolizing enzymes is cultured human hepatocytes, followed by
      liver homogenate fortified with appropriate cofactors. For specific purposes,
      such as the identification of metabolizing enzyme(s), recombinant enzymes can be
      used. Metabolite data from animal in vitro and in vivo experiments, despite known
      species differences, may help pinpoint metabolites that are not apparently
      produced in in vitro human systems, or suggest alternative experimental
      approaches. The range of metabolites detected provides clues regarding the
      enzymes attacking the molecule under study. We also discuss established
      approaches to identify the major enzymes. The last question, regarding
      reliability and robustness of metabolite extrapolations from in vitro to in vivo,
      both qualitatively and quantitatively, cannot be easily answered. There are a
      number of examples in the literature suggesting that extrapolations are generally
      useful, but there are only a few systematic and comprehensive studies to validate
      in vitro-in vivo extrapolations. In conclusion, extrapolation from preclinical
      metabolite data to the in vivo situation is certainly useful, but it is not known
      to what extent.

PMID- 21083175
TI  - Methods for the analysis of fluoroquinolones in biological fluids.
AB  - Methods for the analysis of ten selected fluoroquinolone antibiotics in
      biological fluids are reviewed. Approaches for sample preparation, detection
      methods, limits of detection and quantitation, and recovery information are
      provided for both single analyte and multi-analyte fluoroquinolone methods.

PMID- 21083176
TI  - Analytical methods for the detection of clenbuterol.
AB  - Clenbuterol is therapeutically used for the treatment of pulmonary diseases such
      as bronchial asthma or for tocolytic reasons. In cattle feeding as well as in
      sports it is illicitly misused due to its anabolic properties to promote muscle
      growth. Sample preparation procedures and analytical techniques used for the
      detection of clenbuterol are manifold and vary with the objectives of the
      investigation. Methods for its detection in biological specimens, drug
      preparations, the environment, food and feed products are reported. They are
      mainly based on immunochemical, chromatographic and mass spectrometric
      techniques, or on capillary electrophoresis. Sample preparation primarily
      includes liquid-liquid extraction and solid-phase extraction. Depending on the
      aim of the method clenbuterol can be determined in single- or multi-analyte
      methods. In biological and environmental samples concentrations are generally low
      due to the potency of the drug. Thus, highly sensitive procedures are required
      for expedient analyses.

PMID- 21083177
TI  - Modern bioanalytical methods for the rapid detection of antidepressants: SNRIs
      and SSRIs in human biological samples.
AB  - Serotonin-norepinephrine-reuptake inhibitors (SNRIs) and selective serotonin
      reuptake inhibitors (SSRIs) belong to a new generation of antidepressants used in
      the treatment of depression and other mood disorders. SSRIs act as reuptake
      inhibitors primarily via the inhibition of the neuronal reuptake of serotonin (5
      HT) in the CNS. SNRIs have additional inhibitory activity at noradrenaline
      reuptake sites. Different analytical methods for the routine monitoring and
      toxicological screening of SNRIs and SSRIs have been developed. Rapid
      quantification is a necessity for clinical use, allowing the possibility of
      diagnostics. This review focuses on recent advances of the methods that concern
      the determination of SSRIs and SNRIs in human biological samples. Sample
      preparation methodologies are discussed, because sample pretreatment is the most
      limiting and crucial step in analysis of biological matrices. Furthermore,
      information concerning the mechanism of action, side effects and toxicity are
      also given.

PMID- 21083180
TI  - Development of bioanalysis: a short history.

PMID- 21083182
TI  - Conference report. Recent developments in stable isotope research: joint European
      Stable Isotope User Meeting 2008.
AB  - A rapidly increasing number of applications are currently emerging from stable
      isotope research whilst, at the same time, significant evolution of the
      instrumentation may also be observed. The European stable isotope community
      gathered in Giens, France, to exchange views and discuss recent developments.

PMID- 21083184
TI  - The 2nd Calibration and Validation Group workshop on recent issues in good
      laboratory practice bioanalysis.
AB  - This event was organized by the Calibration and Validation Group (a scientific
      nonprofit organization based in Toronto, Canada) as a 1.5-day workshop for
      contract research organizations and pharmaceutical companies involved in
      providing bioanalytical data for bioavailability, bioequivalence, pharmacokinetic
      and comparability studies.

PMID- 21083185
TI  - Use of microelectrodes for electrochemiluminescent detection in microfluidic
      devices.
AB  - Microfluidic devices allow for fast detection with little reagent consumption.
      They also offer portability and the ability to mimic biological systems.
      Currently, many microfluidic devices are a hybrid of the microchip components,
      such as flow channels and wells, and larger instrumentation. There is a need to
      develop miniaturized detectors for lab-on-a-chip applications. Electrochemical
      detection methods have the advantage of ease of miniaturization. The
      electrochemical method, electrochemiluminescence, has the potential to be
      miniaturized and incorporated into a lab-on-a-chip device. As in other
      electrochemical methods, electrochemiluminescence is straightforward to
      miniaturize, but also possesses the sensitivity of a fluorescence detection
      method. In our laboratory, we have been developing carbon ink microelectrodes as
      the working electrode for a miniaturized electrochemiluminescence system. Since
      the signal is proportional to the electrode area, the challenge has been to
      maximize the signal-to-noise ratio and maintain low detection limits as the
      electrode size decreases.

PMID- 21083186
TI  - A liquid chromatographic-tandem mass spectrometric method for determination of
      artemether and its metabolite dihydroartemisinin in human plasma.
AB  - BACKGROUND: Artemether-lumefantrine is the most widely recommended artemisinin
      based combination treatment for falciparum malaria. Quantification of artemether
      and its metabolite dihydroartemisinin in biological matrices has traditionally
      been difficult, with sensitivity being an issue. RESULTS: A high-throughput
      bioanalytical method for the analysis of artemether and its metabolite
      dihydroartemisinin in human plasma using solid-phase extraction in the 96-well
      plate format and liquid chromatography coupled to positive ion mode tandem mass
      spectroscopy has been developed and validated according to US FDA guidelines. The
      method uses 50 ul plasma and covers the calibration range 1.43-500 ng/ml with a
      limit of detection at 0.36 ng/ml. CONCLUSIONS: The developed liquid
      chromatography-tandem mass spectrometry assay is more sensitive than all previous
      methods despite using a lower plasma volume (50 ul) and is highly suitable for
      clinical studies where plasma volumes are limited, such as pediatric trials.

PMID- 21083187
TI  - Development of an ultra-performance liquid chromatography-tandem mass
      spectrometry micromethod for quantification of lamotrigine in human plasma and
      its use in a bioequivalence trial.
AB  - BACKGROUND: The aim of the present work was to develop a chromatographic
      technique coupled with mass spectrometry for the measurement of lamotrigine in
      plasma. Lamotrigine and guanabenz (internal standard) were measured by selected
      reaction monitoring. The method was validated and applied in a bioequivalence
      trial on 26 female volunteers. Lamotrigine chewable tablets (100 mg) were
      administered and monitored for up to 96 h. RESULTS: The method was linear between
      0.05 and 5.0 ug/ml, with acceptable stability, accuracy and precision. Mean
      maximum plasma concentration was 1.37 ug/ml and was reached at 1.6 h postdose.
      Elimination half-life was 32.7 h. CONCLUSION: Lamotrigine tablets were
      bioequivalent. Ultra-performance liquid chromatography with tandem mass
      spectrometry represents a powerful tool in terms of sensitivity, specificity and
      high-throughput analysis.

PMID- 21083188
TI  - Selection of HILIC columns to handle matrix effect due to phospholipids.
AB  - BACKGROUND: Phospholipids from biological samples are a source of matrix effect
      in liquid chromatography mass spectrometry. While the behavior of phospholipids
      has been documented under reversed-phase chromatography, there is a lack of
      information concerning the selectivity of hydrophilic interaction chromatography
      (HILIC) towards phospholipids. RESULTS: Human plasma extracts were used to
      evaluate retention times and matrix effects associated with phospholipids under
      HILIC conditions. It was observed that phosphatidylcholine and
      lysophosphatidylcholine phospholipid retention times vary greatly between columns
      operated in different HILIC conditions. Therefore, matrix effects associated with
      phospholipids could present a quantitation problem if not evaluated thoroughly
      during method development. CONCLUSIONS: Analytical chemists should carefully
      choose the right combination of sample preparation and chromatographic conditions
      when working under HILIC conditions to avoid variable results.

PMID- 21083189
TI  - Liquid chromatography-tandem mass spectrometry method for the determination of
      meloxicam and its metabolite 5-carboxymeloxicam in human plasma.
AB  - BACKGROUND: To develop and validate a rapid, sensitive and selective liquid
      chromatography-electrospray ionization mass spectrometric method for the
      determination of meloxicam and its metabolite 5-carboxymeloxicam in human plasma.
      RESULTS: A liquid extraction method was chosen for sample clean-up. Meloxicam, 5
      carboxymeloxicam and isoxicam (internal standard) were analyzed on an XBridgeTM
      C18 column with 65% methanol in 10 mM ammonium formate (pH 3.0) and detected in
      selected reaction monitoring mode. The standard curves were linear over the
      concentration range 10-2500 ng/ml for meloxicam and 2-100 ng/ml for 5
      carboxymeloxicam. Matrix effects were practically absent. CONCLUSIONS: This
      method has been successfully applied to the pharmacokinetic study of meloxicam
      and 5-carboxymeloxicam after oral administration of meloxicam (15 mg) to 30
      volunteers.

PMID- 21083190
TI  - LC-MS/MS assay of quinapril and its metabolite quinaprilat for drug
      bioequivalence evaluation: prospective, concurrential and retrospective method
      validation.
AB  - BACKGROUND: The bioequivalence of two pharmaceutical formulations containing 10
      mg quinapril was assessed by assaying the untransformed drug and its active
      metabolite quinaprilat from plasma samples. RESULTS: A gradient elution liquid
      chromatographic separation coupled to positive atmospheric pressure electrospray
      ionization and tandem mass spectrometry detection was used and validated. Sample
      preparation is simple and uses protein precipitation through addition of an
      acetonitrile:methanol (8:2 v/v) mixture. The method has a run time of 6.3 min.
      Carvedilol was used as an internal standard. The multiple reactions monitoring
      mode was used for both quantitation and structural confirmation of target
      compounds. Linear 1/x2-weighted regressions characterize detector response
      function up to concentrations of 1000 ng/ml for quinapril and 2000 ng/ml for
      quinaprilat. Low limits of quantitation of 5 ng/ml for quinapril and 10 ng/ml for
      quinaprilat were found. Intra- and inter-day variability of the results were
      found below 15%. Long- (-20 degrees C/6 months) and short-term (25 degrees C/48
      h) stability of analytes in plasma, as well as freeze and thaw stability (six
      cycles) were demonstrated. CONCLUSION: The method was found to be selective,
      precise, accurate and robust when applied to a large number of unknown samples.

PMID- 21083191
TI  - Digoxin - a therapeutic agent and mechanistic probe: review of liquid
      chromatographic mass spectrometric methods and recent nuances in the clinical
      pharmacology attributes of digoxin.
AB  - Digoxin is an important therapeutic agent for the treatment of congestive cardiac
      failure. In spite of its narrow therapeutic index, digoxin has been used
      extensively by the medical community and, lately, the use of digoxin as a
      mechanistic probe for p-glycoprotein transporter activity has increased. This
      review describes recent trends in the bioanalysis of digoxin, where scores of
      liquid chromatographic-mass spectrometric assays have been successfully employed
      to measure digoxin in preclinical, clinical and mechanistic studies. It provides
      various considerations such as internal standard selection, extraction schemes,
      matrix effect, selectivity evaluation and optimization of mass spectral
      conditions, for example, to enable the development of sound bioanalytical methods
      for digoxin. Some recent updates with regard to clinical pharmacology, absorption
      and disposition aspects of digoxin have been included. Overall, liquid
      chromatographic-mass spectrometric assays represent an important tool for many
      future preclinical, clinical and mechanistic probe studies that would probe
      digoxin with or without other coadministered substrates.

PMID- 21083192
TI  - Ingenious nanoprobes in bioassays.
AB  - This article has a special focus on the broad range of innovative nanoprobes for
      signal amplification and new generations of bioassays. Advances in
      functionalizing gold nanoparticles with oligonucleotides speed up the development
      of a series of new nucleic acid assays. A biobarcode assay allows signal
      amplification by utilizing antibody-coated magnetic beads to concentrate the
      analytes and antibody-coated gold nanoparticle probes to carry a large number of
      oligonucleotides. Novel signal-amplification technologies, based on either new
      classes of nanoprobes consisting of releasable fluorophores or with aggregation
      induced emission features, can also improve the sensitivity of bioassays.
      Advances in synthesis and biofunctionalization of quantum dots with unique
      properties have generated increasingly widespread applications in DNA sorting,
      multiplexing bioassays and fluorescence resonance energy transfer-based sensing.
      Ingenious nanoprobes in bioassays can offer PCR-like sensitivity, high
      selectivity, capacity for massive multiplexing, time efficiency and, most
      importantly, the ability to be performed at the point- of-care.

PMID- 21083193
TI  - Liquid-phase microextraction in bioanalytical sample preparation.
AB  - Liquid-phase microextraction (LPME) emerged in the mid-to-late 1990s, facing up
      to the main shortcomings of the classical liquid-liquid extraction. Since its
      origin, this new technique has been in continuous development driven by its
      successful and widespread use in the analytical sciences. Its inherent
      properties, such as low sample volume requirement, high preconcentration factors
      achieved and excellent sample clean-up, make LPME a very useful technique for
      bioanalytical sample preparation. This review focuses on the main LPME-related
      techniques, predominantly single-drop microextraction and supported hollow-fiber
      LPME, paying particular attention to the bioanalytical applications. A general
      view of the essential trends, including the description of promising extraction
      modes and solvents, is also highlighted.

PMID- 21083194
TI  - New stationary phases for enrichment and separation in the 'omics' era.
AB  - 'Omics' is a general term for a broad discipline of science and engineering
      concerned with analyzing the interactions of biological molecular components in
      various 'omes'. These include genome, proteome, metabolome, expressome and
      interactome. 'Ome' and 'omics' are very convenient handles for describing the
      holistic approach for looking at complex systems. 'Omics' will not only have an
      impact on our understanding of biological processes, but also on the prospect of
      more accurately diagnosing and treating disease. The development of these 'omics'
      has depended on, and has also driven, advances in chromatography and
      electrophoresis, as well as highly sensitive and specific analytical techniques
      to permit the handling of large numbers of samples with high selectivity and
      sensitivity. The development and design of novel stationary phases for selective
      enrichment and separation is one of the key points for establishing a
      successfully running 'omics' platform. Therefore, this review demonstrates the
      application of different new materials developed in our laboratory, such as
      chromatographic stationary phases for selective and sensitive high-speed
      purification, enrichment and separation in genomics, proteomics and metabolomics.

PMID- 21083195
TI  - Pharmacokinetic applications of microdevices and microsampling techniques.
AB  - Pharmacokinetic studies require information regarding drug concentration at
      numerous time points during the process of absorption, distribution, metabolism
      and excretion. In order to obtain reproducible and good-quality data, the
      sampling method is as important as the bioanalytical method. A further difficulty
      in performing pharmacokinetic studies is related to the limited amount of sample
      that can be collected in some cases. Since analytical methods should interfere as
      little as possible with the investigated organism, microsampling techniques are a
      natural choice for pharmacokinetic studies. Accordingly, microdevices and
      microsampling approaches have been used increasingly in recent years for a wide
      variety of analytical applications, including analysis of drugs in biological
      samples. Such techniques not only reduce the amount of reagents needed for
      analysis, but are also faster and less disrupting. This review provides a brief
      overview of contemporary microsampling techniques: collection of small sample
      aliquots, ultrafiltration, microdialysis, solid-phase microextraction, biosensors
      and microfluidics. It is concluded that recent developments in microsampling and
      microdevices promise to streamline pharmacokinetic studies and bring bedside
      monitoring of therapeutic drugs into clinical practice.

PMID- 21083196
TI  - Quantification of polar drugs in human plasma with liquid chromatography-tandem
      mass spectrometry.
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has played an important
      role in quantitative bioanalytical assays. This review summarizes the recent
      progress on quantification of polar drugs in plasma with LC-MS/MS. Various types
      of polar analytes were extracted using protein precipitation or solid-phase
      extraction and precolumn derivatization was utilized in some cases. The analytes
      were then separated using different types of chromatographic method, which
      included reversed-phase chromatography, aqueous normal-phase chromatography,
      hydrophilic interaction liquid chromatography and ion-pairing chromatography.
      Stationary phases of mixed mode and porous graphitic carbon materials are gaining
      acceptance in bioanalytical applications. These technologies can be valuable
      supplements in the quantification of polar drugs in human plasma with LC-MS/MS.
      Matrix effects have also been discussed in this review.

PMID- 21083197
TI  - Factors affecting the stability of drugs and drug metabolites in biological
      matrices.
AB  - Evaluation of the stability of drugs and drug metabolites in a biological matrix
      is a critical element to bioanalytical method validation. It is critical to
      understand the most common factors that affect the stability of such analytes in
      order to properly develop methods for their detection and measurement. The
      degradation of drugs and drug metabolites in samples can occur through either
      reversible or irreversible processes. Common factors that affect this stability
      include temperature, light, pH, oxidation and enzymatic degradation. Special
      considerations are also required when dealing with chiral molecules, deuterated
      internal standards and large biomolecules. Relevant examples of these degradation
      effects and approaches for dealing with them are presented is this review as
      taken from the fields of pharmaceutical testing, clinical research and forensic
      analysis. It is demonstrated through these examples how an understanding of the
      chemical and physical factors that affect sample stability can be used to avoid
      stability problems and to create robust and accurate methods for the analysis of
      drugs and related compounds.

PMID- 21083198
TI  - Chiral determination of antidepressant drugs and their metabolites in biological
      samples.
AB  - The determination of chiral drugs and their metabolites in biological samples is
      key to gaining a full understanding of enantioselective drug action and
      disposition, as well as establishing the advantages of using racemate or isolated
      enantiomers. In this review, methods published in the last 8 years regarding the
      analysis of chiral antidepressant drugs and their metabolites in biological
      fluids (e.g., plasma, urine and cerebrospinal fluid) are reviewed. The importance
      and interest in analyzing the enantiomers of the active compound and its
      metabolites in biological samples are also discussed.

PMID- 21083199
TI  - Bioanalytical hydrophilic interaction chromatography: recent challenges,
      solutions and applications.
AB  - Hydrophilic interaction chromatography (HILIC) has, in recent years, been shown
      to be an important supplement to reversed-phase liquid chromatography for polar
      analytes. HILIC, in conjunction with tandem mass spectrometry (MS/MS), has been
      steadily gaining acceptance in the analysis of polar compounds from complex
      biological matrices. This hyphenated technique offers the advantages of improved
      sensitivity by employing high organic content in the mobile phase, shortened
      sample preparation time with direct injection of the organic-solvent extracts of
      biological samples and the potential for ultra-fast analysis because of low
      column backpressure. This article reviews recent challenges presented by HILIC,
      advancements in the better understanding of retention characteristics of analytes
      with different mobile- and stationary-phase compositions and solutions to ion
      suppression and interference problems encountered in HILIC-MS/MS assays.
      Applications of HILIC-MS/MS are summarized, including those for pharmacokinetic
      studies, metabolic studies, therapeutic drug monitoring and clinical diagnostics.

PMID- 21083200
TI  - Rapid development of novel protein biomarkers using real-time immunoassays.

PMID- 21083202
TI  - 5th Bioanalysis in Clinical Research.

PMID- 21083203
TI  - Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy.

PMID- 21083205
TI  - Elimination of LC-MS/MS matrix effect due to phospholipids using specific solid
      phase extraction elution conditions.
AB  - BACKGROUND: The objective is to find elution conditions using different solid
      phase extraction chemistries to reduce the amount of phospholipids in plasma
      extract, which is associated with matrix effect in LC-MS. RESULTS: Phospholipids'
      recovery was reduced by decreasing the eluents' methanol content applied to
      silica-based and polymer-based reversed-phase solid-phase extraction cartridges
      while 100% acetonitrile applied to the silica-based cartridges drastically
      minimized the phospholipids' elution. Silanol interactions are involved in the
      increased retention of phospholipids with silica-based reversed-phase cartridges
      when using high percentages of ACN in eluents. The bioanalytical usefulness of
      these findings was confirmed by successful extraction recovery of pharmaceutical
      compounds. CONCLUSION: Combinations of specific eluents and reversed-phase solid
      phase extraction cartridges were found to prevent matrix effect due to
      phospholipids.

PMID- 21083206
TI  - Automated sample preparation for regulated bioanalysis: an integrated multiple
      assay extraction platform using robotic liquid handling.
AB  - BACKGROUND: A novel approach for regulated bioanalytical sample preparation has
      been developed to combine multiple types of extraction techniques into one
      integrated and automated sample-preparation suite that pairs a graphical user
      interface with the Hamilton Microlab((r)) STAR robotic liquid handler. RESULTS:
      The multi-assay sample-preparation suite is composed of three bioanalytical
      extraction techniques: protein precipitation, solid-phase extraction and liquid
      liquid extraction. Validation data provided highly reproducible and robust
      results for each respective automated extraction technique. CONCLUSION: The user
      friendly graphical user interface and modular method design provide a flexible
      and versatile approach for routine bioanalytical sample-preparation and is the
      first fully integrated multiple assay sample-preparation suite for regulated
      bioanalysis.

PMID- 21083207
TI  - Evaluation of an isochronic study design for long-term frozen stability
      investigation of drugs in biological matrices.
AB  - Long-term stability is a basic parameter in bioanalytical method validation;
      however, no criteria for conducting long-term stability studies are specified in
      current guidelines. We present an evaluation of a modified statistical approach
      applied to a study design utilizing an isochronic analysis (collection of samples
      to be analyzed at one time point) to determine the long-term stability and,
      further, a comparison with the most widely used continuous design. The presented
      approach has been used in regulated bioanalysis at Lundbeck for the past 7 years
      and has, in this period, been applied to 121 studies; all providing conclusive
      data. The isochronic approach eliminates day-to-day variation, reduces labor and
      adds to the flexibility in the laboratory. The statistical evaluation used is
      based on the relative difference between baseline samples and stability test
      samples as well as 90% confidence intervals for the mean concentration for each
      of the stability test points.

PMID- 21083208
TI  - Critical topics in ensuring data quality in bioanalytical LC-MS method
      development.
AB  - The use of LC-MS for bioanalysis of pharmaceuticals is entering its third decade
      and may be considered to be a mature technology. In many respects this is true,
      considering the advances made in such areas as instrument performance,
      electronics, software and automation of use. However, there remain instrumental
      and noninstrumental areas that require significant attention to ensure data
      quality. Increasing regulatory focus on analytical method performance and
      unaddressed method issues require the bioanalyst to understand those areas that
      most greatly impact data quality. This review will focus on instrumental and
      noninstrumental areas that can influence data quality, including reference
      standard and internal standard quality and physicochemical properties, matrix
      effects, stability in matrix, sample preparation, LC and MS.

PMID- 21083209
TI  - Unwanted immunogenicity: lessons learned and future challenges.
AB  - All biological therapeutics have the potential to induce an immune response in
      recipients of these products. Elicitation of an immune response can result in
      variable clinical impact, ranging from benign to severe adverse effects, a
      diminution in clinical efficacy or, in some cases, hypersensitivity or allergic
      reactions. Consequently, assessment of unwanted immunogenicity is an important
      element of the data required for regulatory submission for product approval.
      However, issues relating to immunogenicity occur throughout the life-cycle of a
      biotherapeutic and need to be considered appropriately when introducing any
      product change(s). Evaluation of immunogenicity of a product requires a well
      considered strategy and a panel of appropriately validated (or 'fit-for-purpose')
      assays for antibody detection and characterization in clinical samples. An
      overview of the bioanalytical methods that are currently being used for
      assessment of immunogenicity of biotherapeutics and the guidance available along
      with some of the challenges facing the industry are discussed in this review.

PMID- 21083210
TI  - Metabolism of anabolic steroids and their relevance to drug detection in
      horseracing.
AB  - The fight against doping in sport using analytical chemistry is a mature area
      with a history of approximately 100 years in horseracing. In common with human
      sport, anabolic/androgenic steroids (AASs) are an important group of potential
      doping agents. Particular issues with their detection are extensive metabolism
      including both phase I and phase II. A number of the common AASs are also
      endogenous to the equine. A further issue is the large number of synthetic
      steroids produced as pharmaceutical products or as 'designer' drugs intended to
      avoid detection or for the human supplement market. An understanding of the
      metabolism of AASs is vital to the development of effective detection methods for
      equine sport. The aim of this paper is to review current knowledge of the
      metabolism of appropriate steroids, the current approaches to their detection in
      equine sport and future trends that may affect equine dope testing.

PMID- 21083211
TI  - Multidimensional approaches in LC and MS for phospholipid bioanalysis.
AB  - The advancement of both LC and MS has contributed significantly to phospholipid
      analysis. Two major trends of developments have emerged in the past decade:
      application of dedicated online (or offline) LC-MS techniques including 2D and
      sophisticated chromatographic separations, and the development of so-called
      shotgun lipidomics represented by multidimensional MS-based techniques. However,
      neither of these techniques have been shown to be a universal solution for the
      increasing demand on the comprehensive information of lipid metabolomics in
      lipidomics studies. This is partially due to the intrinsic complexity of
      naturally occurring phospholipids in practice. It is evident that either
      chromatography or MS has to go multidimensional in order to fulfil this goal.
      This review focuses on recent developments of multidimensional MS, LC-MS and
      chromatographic approaches for lipidomics analysis. The perspectives and
      retrospectives of chromatography and MS in these aspects will be reviewed and
      discussed.

PMID- 21083212
TI  - Therapeutic monoclonal antibody concentration monitoring: free or total?
AB  - Most therapeutic monoclonal antibodies are designed to bind a specific antigen to
      elicit pharmacological effects. Accurate quantification of a therapeutic
      monoclonal antibody in biological matrices is essential for assessing its
      pharmacokinetics and selecting an effective dosing regimen. Therapeutic
      antibodies may exist in free, partially bound and fully bound forms in the
      bloodstream. The choice of which form(s) to measure and how to measure them is
      gaining much attention with the increase in the number of soluble therapeutic
      targets. This article will review the bioanalytical methods used in supporting
      the clinical development of the US FDA-approved therapeutic monoclonal antibodies
      and also discuss how different factors, such as assay format, target and antibody
      concentrations, and sample dilutions, can have an impact on the measurement of
      each form of antibody. Appreciation of which form of drug is being measured and
      what factors may impact measurement under different conditions are important for
      interpretation of the pharmacokinetics of therapeutic antibodies.

PMID- 21083213
TI  - LC-MS/MS for immunosuppressant therapeutic drug monitoring.
AB  - Due to their narrow therapeutic indices and highly variable pharmacokinetics,
      therapeutic drug monitoring is necessary to individualize immunosuppressant
      dosage following organ transplantation. Until recently, monitoring was performed
      primarily using immunoassays, however, there is an increasing shift to HPLC
      coupled with MS/MS, due to its greater sensitivity and specificity. Online sample
      clean-up with either a single analytical column or with 2D chromatography
      significantly reduces manual handling and is essential to minimize matrix effects
      and maximize specificity and, coupled with rapid chromatography, allows the
      simultaneous analysis of the major immunosuppressants, with rapid sample
      throughput. Thus, LC-MS/MS is an attractive and versatile technique that
      facilitates rapid development of analytical methods, including new
      immunosuppressants as they become approved for clinical use.

PMID- 21083216
TI  - Cancer-related forecast biomarkers: a topic in focus of the Worldwide Innovative
      Network in Personalized Cancer Medicine (WIN).

PMID- 21083218
TI  - Therapeutic drug monitoring in cancer chemotherapy.
AB  - For a select number of drugs, proper management of patients includes monitoring
      serum or plasma concentrations of the drugs and adjusting the doses accordingly -
      this practice is referred to as therapeutic drug monitoring (TDM). The need for
      TDM arises when pharmacokinetic variability of drugs is not easily accounted for
      by common clinical parameters. Many chemotherapeutic drugs have large
      interindividual variability, yet TDM is not commonplace in chemotherapy
      management. This review will discuss pharmacokinetics in the context of
      chemotherapeutic drugs, examine the few instances where TDM is currently used in
      the field of oncology and propose other drugs where TDM might be useful for dose
      adjustments in the management of chemotherapy.

PMID- 21083217
TI  - Derivation of cancer diagnostic and prognostic signatures from gene expression
      data.
AB  - The ability to compare genome-wide expression profiles in human tissue samples
      has the potential to add an invaluable molecular pathology aspect to the
      detection and evaluation of multiple diseases. Applications include initial
      diagnosis, evaluation of disease subtype, monitoring of response to therapy and
      the prediction of disease recurrence. The derivation of molecular signatures that
      can predict tumor recurrence in breast cancer has been a particularly intense
      area of investigation and a number of studies have shown that molecular
      signatures can outperform currently used clinicopathologic factors in predicting
      relapse in this disease. However, many of these predictive models have been
      derived using relatively simple computational algorithms and whether these models
      are at a stage of development worthy of large-cohort clinical trial validation is
      currently a subject of debate. In this review, we focus on the derivation of
      optimal molecular signatures from high-dimensional data and discuss some of the
      expected future developments in the field.

PMID- 21083219
TI  - Biomarkers in cancer micrometastasis: where are we at?
AB  - Despite considerable advances in the field of solid tumors, disseminated
      malignancy remains the cause of the vast majority of cancer-related deaths. In
      patients with no overt metastasis, early spread of tumor cells is usually
      undetected by current imaging technologies. In addition, the metastatic process
      is complex and depends on multiple interactions (crosstalk) of disseminating
      tumor cells with the individual homeostatic mechanisms, which the tumor cells can
      usurp. Despite these many variables, a flurry of surrogate biomarkers to detect
      micrometastasis has been developed in the last decade. These biomarkers open
      avenues for understanding cancer dormancy and metastasis, have the potential to
      provide novel therapeutic targets and may help predict outcome and therapeutic
      decisions at diagnosis and during follow-up of cancer patients. This review
      focuses on ongoing efforts to unravel metastasis biology, surrogate biomarkers
      currently investigated to monitor micrometastasis and tools used to identify,
      quantify and determine their capacity to efficiently establish metastasis.

PMID- 21083220
TI  - Analytical methodologies utilized in the search for chronic disease biomarkers.

PMID- 21083221
TI  - Analytical confidence and insomnia.

PMID- 21083222
TI  - Bioanalytical method validation: notable points in the 2009 draft EMA Guideline
      and differences with the 2001 FDA Guidance.

PMID- 21083224
TI  - Research spotlight: research at the Biomedical Analysis Group of the University
      Utrecht, The Netherlands.

PMID- 21083226
TI  - Capillary separations in metabolomics.
AB  - Capillary-based separations offer increased resolution, low mass LOD and, in the
      case of MS, higher sensitivity. The chemical diversity and wide dynamic range of
      the metabolome requires systems that offer breadth and depth of analysis. In this
      review, we will highlight novel chemical innovations, technological advancements
      and various applications of capillary separations in the field of metabolomics.

PMID- 21083227
TI  - Bioanalysis of new designer drugs.
AB  - Since the late 1990s the illicit drug market has undergone considerable change:
      along with the traditional drugs of abuse that still dominate, more than 100
      psychotropic substances designed to bypass controlled substances legislation have
      appeared and led to intoxications and fatalities. Starting from the huge class of
      phenylalkylamines, containing many subgroups, the spectrum of structures has
      grown from tryptamines, piperazines, phenylcyclohexyl derivates and
      pyrrolidinophenones to synthetic cannabinoids and the first synthetic cocaine.
      Due to the small prevalence and high number of unknown substances, the detection
      of new designer drugs is a challenge for clinical and forensic toxicologists.
      Standard screening procedures might fail because a recently discovered or yet
      unknown substance has not been incorporated in the library used. Nevertheless,
      many metabolism studies, case reports, screening methods and substance-profiling
      papers concentrating on single compounds have been published. This review
      provides an overview of the developed bioanalytical and analytical methods, the
      matrices used, sample-preparation procedures, concentration of analytes in case
      of intoxication and also gives a resume of immunoassay experiences. Additionally,
      six screening methods for biological matrices with a larger spectrum of analytes
      are described in more detail.

PMID- 21083228
TI  - Welcome to MIST and bioanalysis. Foreword.

PMID- 21083229
TI  - Importance of metabolite testing in regulated bioanalysis.

PMID- 21083232
TI  - Conference report: Inaugural Applied Pharmaceutical Analysis: India 2010
      conference.
AB  - The inaugural Applied Pharmaceutical Analysis-India (APA-India) conference was
      held between 21 and 24 February 2010 in Hyderabad, India. The theme of the 2010
      APA-India meeting was "The best of bioanalytical science in India: the role of
      bioanalysis and absorption, distribution, metabolism and excretion in
      translational medicine". The conference brought together scientists from across
      India and the rest of the world to stimulate discussion in the areas of discovery
      bioanalysis, new technologies, regulated bioanalysis and biotransformation, as
      applied to pharmaceutical analysis in India, the USA and other parts of the
      world. A total of 37 podium presentations and three webinars were presented at
      the 2010 APA-India meeting. The analytical tool of focus was MS with an emphasis
      on application to the Department of Drug Metabolism and Pharmacokinetics studies
      in a globalized pharmaceutical industry.

PMID- 21083233
TI  - Best practices in a tiered approach to metabolite quantification: views and
      recommendations of the European Bioanalysis Forum.
AB  - The relationship between the exposure to drug metabolites and overall drug safety
      has become an integral part of the drug-development process. In-depth discussions
      in the scientific community, as well as recent guidelines on Drug Safety Testing
      of Metabolites from the US FDA (often referred to as the MIST guidance and ICH
      M3(R2) from the International Conference on Harmonization (ICH), has brought
      clarity to the regulatory requirements of the sponsor company in providing
      documentation on circulating levels of qualifying metabolites. However, less
      attention has been given to the challenges now faced by the bioanalytical
      community in supporting these new guidance policies. In this paper, the European
      Bioanalysis Forum (EBF) is providing a recommendation on which quality standards
      to apply when assessing the (relative) abundance or absolute concentrations of
      metabolites. This paper is the result of both an intensive consultation within
      the EBF (through internal surveys amongst EBF member companies and discussions)
      and consultation of the broader bioanalytical community (through discussions at
      international conferences). These recommendations will provide an increased
      understanding of how to apply a tiered approach to metabolite quantification as
      part of the bioanalytical strategy. As such, it aims to provide support to the
      bioanalytical community on the appropriate level of validation required at each
      stage of the drug-development process.

PMID- 21083234
TI  - A radiocalibration method with pseudo internal standard to estimate circulating
      metabolite concentrations.
AB  - BACKGROUND: It has become important for metabolism scientists to identify and
      quantify prominent circulating human metabolites in order to develop a metabolite
      safety-qualification package that meets regulatory standards. Often these
      metabolites cannot be analyzed using traditional bioanalytical methods because a
      standard is not available. RESULTS: A radiocalibration method is described that
      can estimate circulating metabolite concentrations in nonradioactive human and
      animal plasma. The key to this method is application of a pseudo internal
      standard (PIS) that is present in both radioactive reference and nonradioactive
      (i.e., unknown) samples. Metabolite exposure in the unknown samples is estimated
      from measured PIS exposure using a relative molar ratio established between the
      metabolite and PIS (usually parent drug). CONCLUSION: Two case studies
      demonstrate that the method can be used to establish human metabolite safety
      coverage in animal plasma and method validation is demonstrated by comparing
      estimated metabolite concentrations in human plasma with concentrations obtained
      directly using a metabolite calibration curve.

PMID- 21083235
TI  - Assessing covalent binding of reactive drug metabolites by complete protein
      digestion and LC-MS analysis.
AB  - BACKGROUND: Covalent binding by reactive drug metabolites represents a poorly
      understood cause of drug toxicity. Currently, assessing protein covalent binding
      usually entails the use of radioactive drug and therefore has limited
      applicability in drug discovery. Several marketed drugs are known to form
      reactive metabolites and have been shown to covalently bind to proteins. RESULTS:
      In this article, we describe a new method for the analysis of reactive metabolite
      protein binding by MS using a strategy of complete digestion of microsomal
      proteins into free amino acids. Immobilized pronase was found to be the best
      method for complete digestion in terms of stability of amino acid modifications
      as well as minimized spectral background. CONCLUSION: Modified cysteine residues
      were identified for four tested drug compounds known to form reactive metabolites
      following in vitro microsomal incubations and accurate mass measurements by LC-MS
      analysis.

PMID- 21083236
TI  - Metabolites: have we MIST out the importance of structure and physicochemistry?
AB  - The analysis of circulating metabolites is driven by the need to complete a
      comprehensive PK/PD exploration of the activity of a drug. When detected and
      identified, circulating metabolites should be considered from their
      concentration, structure (relationship to parent and known structure-activity
      relationships) and physicochemistry (in particular lipophilicity, polar surface
      area and charge). All these considerations help to determine the likelihood of
      the metabolites exerting on and off target pharmacology, which may contribute to
      the overall efficacy and side effects (including toxicity) of the drug.
      Circulating metabolites do not directly allow an estimate of the actual amounts
      formed (or proportion of the dose) of a particular metabolite. The amount formed
      is useful to estimate the chances of possible toxicity, in clinical use, from
      reactive metabolites. Such metabolites are not usually detectable in their
      reactive, unstable form. They are readily characterized, however, and quantified
      as downstream excreted metabolites such as glutathione conjugates. Clinical use
      of a drug is often specified for special populations (polymorphic drug
      metabolizing enzymes) and co-medications (drug-drug interactions). The early
      investigation of these uses in vitro enzymology assessments. It is important to
      ensure that the in vitro pathways match those seen in humans in vivo. Assignment
      of clearance routes is facilitated by assessment of the proportion of parent drug
      cleared by the various routes using excreted metabolite data.

PMID- 21083237
TI  - Looking back through the MIST: a perspective of evolving strategies and key focus
      areas for metabolite safety analysis.
AB  - The publication of the US FDA MIST guidance document in 2008 reignited the debate
      around the most appropriate strategies to underwrite metabolite safety for novel
      compounds. Whilst some organizations have suggested that the guidelines
      necessitate a paradigm shift to more thorough metabolite analysis during early
      development, an evaluation of historical practices shows that the principles of
      the guidelines have always largely underpinned metabolism studies within the
      pharmaceutical industry. Therefore, it is argued that existing practices, when
      coupled to appropriate emerging analytical tools and a case-by-case consideration
      of the relevance of the generated metabolism data in terms of structure,
      physicochemisty, abundance and activity, represent a fit-for-purpose approach to
      metabolite-safety assessments.

PMID- 21083238
TI  - Overview of metabolite safety testing from an industry perspective.
AB  - Regulatory guidelines on MIST were initially established in 2005 and finalized in
      2008 by the US FDA and this has led to much discussion and debate on how to apply
      these recommendations in today's resource-constrained pharmaceutical environment.
      There are four aspects of MIST that impact on the field of bioanalysis:
      definition of a disproportionate human metabolite, establishment of nonclinical
      (animal) safety coverage for important human metabolites, degree of rigor in
      validation of bioanalytical methods to quantify metabolites when synthetic
      standards are available, and semiquantitation of metabolites when synthetic
      standards are not available. In this manuscript, each of these points has been
      addressed from a pharmaceutical industry standpoint, including a perspective on
      the necessary convergence of the fields of metabolite safety testing and
      bioanalysis.

PMID- 21083239
TI  - NMR spectroscopy as a tool to close the gap on metabolite characterization under
      MIST.
AB  - Withdrawals from the market due to unforeseen adverse events have triggered
      changes in the way therapeutics are discovered and developed. This has resulted
      in an emphasis on truly understanding the efficacy and toxicity profile of new
      chemical entities (NCE) and the contributions of their metabolites to on-target
      pharmacology and off-target receptor-mediated toxicology. Members of the
      pharmaceutical industry, scientific community and regulatory agencies have held
      dialogues with respect to metabolites in safety testing (MIST); and both the US
      FDA and International Conference on Harmonisation have issued guidances with
      respect to when and how to characterize metabolites for human safety testing.
      This review provides a brief overview of NMR spectroscopy as applied to the
      structure elucidation and quantification of drug metabolites within the drug
      discovery and development process. It covers advances in this technique,
      including cryogenic cooling of detection circuitry for enhanced sensitivity,
      hyphenated LC-NMR techniques, improved dynamic range through new solvent
      suppression pulse sequences and quantitation. These applications add to the
      already diverse NMR toolkit and further anchor NMR as a technique that is
      directly applicable to meeting the requirements of MIST guidelines.

PMID- 21083240
TI  - Production of human phase 1 and 2 metabolites by whole-cell biotransformation
      with recombinant microbes.
AB  - Cytochrome P450 enzymes (CYPs or P450s) are the most important enzymes involved
      in the phase I metabolism of drugs and poisons in humans, while UDP
      glycosyltransferases catalyze the majority of phase II reactions. In addition, a
      number of other enzymes or enzyme families contribute to the metabolism of
      xenobiotica, including alcohol dehydrogenase, aldehyde dehydrogenase, ester and
      amide hydrolases, epoxide hydrolase and flavine monooxygenases, as well as
      sulfotransferases, catechol-O-methyltransferase and N-acetyltransferase. A
      thorough understanding of their activity and of the properties of the metabolites
      they form is an essential prerequisite for the assessment of drug-caused side
      effects or toxicity. In this context of MIST, efficient production systems are
      needed to permit the large-scale production of human drug metabolites. As
      classical chemical synthesis cannot always provide these metabolites,
      biotechnological approaches have been developed that typically employ the
      recombinant expression of human drug-metabolizing enzymes. This review summarizes
      the current knowledge regarding whole-cell biotransformation processes that make
      use of such an approach.

PMID- 21083241
TI  - Novel MS solutions inspired by MIST.
AB  - To improve patient safety and to help avoid costly late-stage failures, the
      pharmaceutical industry, along with the US FDA and International Committee on
      Harmonization (ICH), recommends the identification of differences in drug
      metabolism between animals used in nonclinical safety assessments and humans as
      early as possible during the drug-development process. LC-MS is the technique of
      choice for detection and characterization of metabolites, however, the widely
      different LC-MS response observed for a new chemical entity (NCE) and its
      structurally related metabolites limits the direct use of LC-MS responses for
      quantitative determination of NCEs and metabolites. While no method provides
      completely accurate universal response, UV, corona charged aerosol detection
      (CAD), radioactivity, NMR and low-flow (< 20 ul/min) nanospray approaches provide
      opportunities to quantify metabolites in the absence of reference standards or
      radiolabeled material with enough precision to meet the needs of early clinical
      development.

PMID- 21083242
TI  - Addressing metabolite safety during first-in-man studies using 14C-labeled drug
      and accelerator mass spectrometry.
AB  - Active drug metabolites formed in humans but present in relatively low abundance
      in preclinical species can lead to unpredicted adverse effects during clinical
      use. The regulatory guidelines in recent years have therefore required that the
      metabolism of a drug be quantitatively compared between preclinical species and
      human at the earliest practicable stage of drug development. Amongst the variety
      of methods available, inclusion of low radioactive doses of 14C drug in first-in
      man studies coupled to the sensitive analytical technology of accelerator MS
      (AMS) has found utility. Measurement of 14C by AMS allows for quantification of
      metabolites, even if their structures are unknown, and, when used in conjunction
      with LC-MS, can provide both quantitative and structural data. This review
      examines a typical approach to using AMS and associated analytical methods in
      addressing the regulatory guidelines and discusses a number of possible scenarios
      including the question of steady state.

PMID- 21083243
TI  - Regulatory observations in bioanalytical determinations.
AB  - The concept of measuring analytes in biological media is a long-established area
      of the quantitative sciences that is employed in many sectors. While academic
      research and R&D units of private firms have been in the forefront of developing
      complex methodologies, it is the regulatory environment that has brought the
      focus and rigor to the quality control of the quantitative determination of drug
      concentration in biological samples. In this article, the author examines the
      regulatory findings discovered during the course of several years of auditing
      bioanalytical work. The outcomes of these findings underscore the importance of
      quality method validation to ensure the reliability of the data generated. The
      failure to ensure the reliability of these data can lead to potential risks in
      the health management of millions of people in the USA.

PMID- 21083244
TI  - Welcome to 'microdosing'.

PMID- 21083245
TI  - Human microdosing for the prediction of patient response.

PMID- 21083246
TI  - Trends in microdosing and other exploratory human pharmacokinetic studies for
      early drug development.

PMID- 21083248
TI  - Interview: Interview with Professor Malcolm Rowland.
AB  - Malcolm Rowland is Professor Emeritus and former Dean of the School of Pharmacy
      and Pharmaceutical Sciences and a member and former director (1996-2000), of the
      Centre for Applied Pharmacokinetic Research, University of Manchester. He holds
      the positions of Adjunct Professor, School of Pharmacy, University of California,
      San Francisco; Member, Governing Board, EU Network of Excellence in
      Biosimulation; Founder member of NDA Partners; academic advisor to a
      Pharmaceutical initiative in prediction of human pharmacokinetics and Scientific
      Advisor to the EU Microdose AMS Partnership Program. He was President of the EU
      Federation for Pharmaceutical Sciences (1996-2000); Vice-President of the
      International Pharmaceutical Federation (2001-2009) and a Board Member of the
      National Centre for the Replacement, Refinement and Reduction of Animals in
      Research (NC3Rs, 2004-2008). He received his degree in Pharmacy and PhD at the
      University of London and was on faculty (School of Pharmacy, University of
      California San Francisco [1967-1975]) before taking up a professorship at
      Manchester. His main research interest is physiologically based pharmacokinetics
      and its application to drug discovery, development and use. He is author of over
      300 scientific articles and co-author, with TN Tozer, of the textbooks Clinical
      Pharmacokinetics and Pharmacodynamics: Concepts and Applications and Introduction
      to Pharmacokinetics and Pharmacodynamics. He was editor of the Journal of
      Pharmacokinetics and Pharmacodynamics (formerly Journal of Pharmacokinetics and
      Biopharmaceutics, 1973-2007) and, since 1977, has organized regular residential
      workshops in pharmacokinetics.

PMID- 21083249
TI  - Opinion: Microdosing: safer clinical trials and fewer animal tests.

PMID- 21083250
TI  - Development of 2D chiral chromatography with accelerator mass spectrometry for
      quantification of (14)C-labeled R- and S-verapamil in plasma.
AB  - BACKGROUND: A microdose study was performed where 50 ug R/S-(14)C-verapamil was
      dosed intravenously to human volunteers. In order to quantify the individual R-
      and S-enantiomers in human plasma a 2D chiral HPLC method with subsequent
      analysis by accelerator mass spectrometry was verified. RESULTS: R/S-verapamil
      was separated on a C18 column and the isolated fraction was applied to a chiral
      column where the verapamil enantiomers were separated. Experimental recovery
      (~73% [coefficient of variation {CV} = 16%] and 66% [CV = 21%] for R- and S
      verapamil, respectively) was accounted for by the use of internal standardization
      from the fluorescence response of nonlabeled R- and S-verapamil. The precision of
      the assay ranged from 4.1 to 15.9% CV and the limit of quantitation was 1.95-4.81
      pg/ml for R-verapamil and 1.76-3.34 pg/ml for S-verapamil. CONCLUSION: This
      method was successfully applied to the analysis of R- and S-verapamil in human
      plasma.

PMID- 21083251
TI  - Sensitivity and proportionality assessment of metabolites from microdose to high
      dose in rats using LC-MS/MS.
AB  - BACKGROUND: The objective of this study was to evaluate the sensitivity
      requirement for LC-MS/MS as an analytical tool to characterize metabolites in
      plasma and urine at microdoses in rats and to investigate proportionality of
      metabolite exposure from a microdose of 1.67 ug/kg to a high dose of 5000 ug/kg
      for atorvastatin, ofloxacin, omeprazole and tamoxifen. RESULTS: Only the
      glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole
      and the hydration metabolite of tamoxifen were characterized in rat plasma at
      microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and
      tamoxifen appeared to increase in a nonproportional manner with increasing doses.
      Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and
      lactone, increased proportionally with increasing doses. CONCLUSION: LC-MS/MS has
      demonstrated its usefulness for detecting and characterizing the major
      metabolites in plasma and urine at microdosing levels in rats. The exposure of
      metabolites at microdose could not simply be used to predict their exposure at
      higher doses.

PMID- 21083252
TI  - Microdosing in early lead discovery.
AB  - Microdosing provides a tool to enhance drug development by initiating human
      studies prior to Phase I studies. The purpose is to assist in the go versus no-go
      decision-making process and to eliminate early ineffective compounds from the
      drug pipeline. Selection of multiple potential leads can be performed at the
      clinical stage instead of in preclinical studies. The microdosing approach can be
      easily used for a molecularly targeted potential drug compound with a known
      mechanism of action. It provides useful data regarding accessibility and
      biodistribution that can be used in many estimations benefiting the development
      of the molecule. In addition, steady state and genetic investigations are
      becoming possible. Microdosing has a sparing effect on timelines and costs,
      however, the real importance is not yet known because, although it is known to be
      widely performed, only a few original reports have been published.

PMID- 21083253
TI  - Practical experience of using human microdosing with AMS analysis to obtain early
      human drug metabolism and PK data.
AB  - The background to human microdosing or Phase 0 studies is reviewed, focusing
      particularly on the information that such studies can provide in the context of
      exploratory clinical development. Examples are provided of the microdose
      validation studies known as the Consortium for Resourcing and Evaluating AMS
      Microdosing trial and EU Microdosing AMS Partnership Programme, which
      demonstrated that there was good dose proportionality between microdose and
      pharmacological dose pharmacokinetics. When microdosing was applied to ten
      development drugs, it was found that all ten molecules showed dose
      proportionality between the microdose and the pharmacological dose. The majority
      of microdose studies have used accelerator mass spectrometry (AMS) analysis and
      only these studies that are considered here; AMS provides information on all
      metabolites, even if these are minor. There is now sufficient scientific data to
      justify microdose studies being routinely conducted as part of the drug
      development process.

PMID- 21083254
TI  - Early human ADME using microdoses and microtracers: bioanalytical considerations.
AB  - Quantitative assessment of metabolites of drug candidates in early-phase clinical
      development presents an analytical challenge when methods, standards and assays
      are not yet available. Radioisotopic labeling, principally with radiocarbon
      ((14)C), is the preferred method for discovering and quantifying the absolute
      yields of metabolites in the absence of reference material or a priori knowledge
      of the human metabolism. However, the detection of (14)C is inefficient by decay
      counting methods and, as a result, high radiological human (14)C-doses had been
      needed to assure sensitive detection of metabolites over time. High radiological
      doses and the associated costs have been a major obstacle to the routine (and
      early) use of (14)C despite the recognized advantages of a (14)C-tracer for
      quantifying drug metabolism and disposition. Accelerator mass spectrometry
      eliminates this long-standing problem by reducing radioactivity levels while
      delivering matrix-independent quantitation to attomole levels of sensitivity in
      small samples or fractionated isolates. Accelerator mass spectrometry and trace
      (14)C-labeled drugs are now used to obtain early insights into the human
      metabolism of a drug candidate in ways that were not previously practical. With
      this article we describe some of our empirically based approaches for regualted
      bioanalysis and offer perspectives on current applications and opportunities for
      the future.

PMID- 21083255
TI  - Accelerator mass spectrometry best practices for accuracy and precision in
      bioanalytical (14)C measurements.
AB  - Accelerator mass spectrometers have an energy acceleration and charge exchange
      between mass definition stages to destroy molecular isobars and allow single ion
      counting of long-lived isotopes such as (14)C (t1/2=5370 years.). 'Low' voltage
      accelerations to 200 kV allow laboratory-sized accelerator mass spectrometers
      instruments for bioanalytical quantitation of (14)C to 2-3% precision and
      accuracy in isolated biochemical fractions. After demonstrating this accuracy and
      precision for our new accelerator mass spectrometer, we discuss the critical
      aspects of maintaining quantitative accuracy from the defined biological fraction
      to the accelerator mass spectrometry quantitation. These aspects include
      sufficient sample mass for routine rapid sample preparation, isotope dilution to
      assure this mass, isolation of the carbon from other sample combustion gasses and
      use of high-efficiency biochemical separations. This review seeks to address a
      bioanalytical audience, who should know that high accuracy data of physiochemical
      processes within living human subjects are available, as long as a (14)C
      quantitation can be made indicative of the physiochemistry of interest.

PMID- 21083256
TI  - Analytical validation of accelerator mass spectrometry for pharmaceutical
      development.
AB  - The validation parameters for pharmaceutical analyses were examined for the
      accelerator mass spectrometry measurement of (14)C/C ratio, independent of
      chemical separation procedures. The isotope ratio measurement was specific (owing
      to the (14)C label), stable across samples storage conditions for at least 1
      year, linear over four orders of magnitude with an analytical range from 0.1
      Modern to at least 2000 Modern (instrument specific). Furthermore, accuracy was
      excellent (between 1 and 3%), while precision expressed as coefficient of
      variation was between 1 and 6% determined primarily by radiocarbon content and
      the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1
      and 10 attomoles of (14)C, respectively (which can be expressed as compound
      equivalents) and for a typical small molecule labeled at 10% incorporated with
      (14)C corresponds to 30 fg equivalents. Accelerator mass spectrometry provides a
      sensitive, accurate and precise method of measuring drug compounds in biological
      matrices.

PMID- 21083257
TI  - Ocular microdialysis: a continuous sampling technique to study pharmacokinetics
      and pharmacodynamics in the eye.
AB  - The unique anatomy and physiology of the eye present many challenges to the
      successful development and delivery of ophthalmic drugs. Any therapeutic strategy
      developed to control the progression of anterior and posterior segment diseases
      requires continuous monitoring of effective drug concentrations in the relevant
      ocular tissues and fluids. Ocular microdialysis has gained popularity in recent
      years due to its ability to continuously monitor drug concentrations and
      substantially reduce the number of animals needed. The intrusive nature of ocular
      microdialysis experimentation has restricted these studies to animal models. This
      review article intends to highlight various aspects of ocular microdialysis and
      its relevance in examining the disposition of drugs in the anterior and posterior
      segments.

PMID- 21083258
TI  - Microdosing: current and the future.
AB  - The concept of microdosing has been around for approximately 10 years. In this
      time there have been an increasing number of drugs reported in the literature
      where the pharmacokinetics at a microdose have been compared with those observed
      at a therapeutic dose. Currently, approximately 80% of the microdose
      pharmacokinetics available in the public domain have been shown to scale to those
      observed at a therapeutic dose, within a twofold difference. Microdosing is now
      being extended into areas of drug development other than purely pharmacokinetic
      prediction. Microdosing has been applied to the study of drug-drug interactions
      by giving human volunteers a microdose of the candidate drug before and after the
      administration of a drug known to inhibit or induce certain enzymes, such as the
      cytochrome P450s. Early data on the metabolism of a drug candidate can be
      obtained by administering a (14)C-drug to human volunteers and comparing the
      plasma concentration-time curves for total (14)C and unchanged parent compound.
      Full metabolic profiles can be generated as an early indication of the drug's
      metabolism in humans, prior to Phase 1 clinical studies. Microdosing is also
      being applied to situations where the concentration of a drug in cell or tissue
      types is key to its efficacy. The application of microdosing as a tool in drug
      development is therefore widening into new and previously unforeseen fields.

PMID- 21083261
TI  - Request for global harmonization of the guidance for Bioanalytical Method
      Validation and sample analysis.

PMID- 21083262
TI  - International harmonization of bioanalytical guidance.

PMID- 21083263
TI  - Towards harmonized regulations for bioanalysis: moving forward!

PMID- 21083264
TI  - Integrated systems for quantifying metabolite biomarkers of hepatic bioactivation
      in patients.

PMID- 21083266
TI  - The broadening scope of validation: towards best practices in the world of
      bioanalysis.

PMID- 21083267
TI  - Impacting biology through analysis.

PMID- 21083268
TI  - Drug bioanalysis and biomarker discovery at the Commissariat a l'energie atomique
      et aux energies alternatives.

PMID- 21083270
TI  - Impact of matrix-associated soluble factors on the specificity of the
      immunogenicity assessment.
AB  - BACKGROUND: Specificity and sensitivity are essential in assays for
      immunogenicity assessment of biotherapeutics. Nonspecific interactions from
      excess therapeutic or anti-therapeutic antibody, soluble ligands (e.g., target
      receptor), or serum proteins associated with autoimmune conditions (e.g.,
      rheumatoid factor) in samples can impact the detection of a true anti-therapeutic
      response. RESULTS: Electrochemiluminescence-based bridging assay formats could
      eliminate the interference due to rheumatoid factor with no pretreatment with
      Melon GelTM or aggregated IgG. The interference due to soluble factors was not
      platform specific for the four therapeutics evaluated in this study. CONCLUSION:
      Melon Gel pretreatment and avidin high-bind (Meso Scale Discovery) plates can
      effectively reduce interference due to rheumatoid factor in ELISA- and
      electrochemiluminescence-based assays, respectively. Excess levels of therapeutic
      and anti-therapeutic antibodies in bridging assays can impact assay specificity.

PMID- 21083271
TI  - Effective screening approach to select esterase inhibitors used for stabilizing
      ester-containing prodrugs analyzed by LC-MS/MS.
AB  - BACKGROUND: Analysis of prodrugs, with their short half-lives, especially ester
      containing ones, poses a unique challenge in developing and validating
      bioanalytical assays for nonclinical and clinical studies. A screening approach
      is needed to expeditiously select esterase inhibitors for stabilizing them during
      sample collection and processing. RESULTS: The screening process consisted of
      three steps. Initially, nine different esterase inhibitors were screened at three
      different plasma concentrations against an ester prodrug. Four inhibitors were
      chosen for the next step, in which plasma pH and processing temperature were
      optimized. Finally, whole-blood stability of the prodrug was evaluated. Three
      inhibitors with optimized plasma pH and processing temperature were selected for
      further bioanalytical assay development. CONCLUSION: An effective approach was
      successfully developed to promptly select suitable esterase inhibitors for
      stabilizing ester-containing prodrugs.

PMID- 21083272
TI  - Simultaneous bioanalysis of a phosphate prodrug and its parent compound using a
      multiplexed LC-MS method.
AB  - BACKGROUND: Bioanalytical support of drug-discovery efforts increasingly requires
      more complex multiple component analysis, including the bioanalysis of drugs,
      prodrugs and metabolites. Just as the physiochemical properties of these
      components may differ widely from each other, optimal LC and MS conditions,
      including polarity, can also vary greatly among the analytes of interest, thus
      presenting significant challenges during quantitative LC-MS-based bioanalysis. A
      single compromised method for the determination of all analytes may sacrifice
      sensitivity or chromatographic conditions for one analyte in order to achieve
      adequate results for another. Manually switching between assay conditions to
      analyze samples under separately optimized conditions for individual compounds
      can be time consuming. RESULTS: The method presented here addresses the problem
      of differential analyte optimization using a multiplexed approach for
      simultaneous quantitative bioanalysis of multiple analytes in the same sample,
      employing a mixed mode of both turbulent- and laminar-flow chromatography.
      CONCLUSION: The approach is illustrated with the quantitation of a lipophilic
      drug and its hydrophilic phosphate ester prodrug in a biological matrix under
      individually optimized LC-MS conditions.

PMID- 21083273
TI  - Evaluation of the relationship between a pharmaceutical compound's distribution
      coefficient, log D and adsorption loss to polypropylene in urine and CSF.
AB  - BACKGROUND: The distribution coefficient, D, is a physicochemical property used
      to determine the partitioning of compounds between aqueous and hydrophobic media
      at a given pH. RESULTS: A clear relationship was observed between the calculated
      pH-dependent distribution coefficient of six representative pharmaceutical probe
      compounds and their propensity to partition between a relatively hydrophobic
      polypropylene surface and the aqueous matrices, human urine or human
      cerebrospinal fluid (CSF). Compound log D cut-off values of 1.5 and 3.8 for urine
      and CSF, respectively, were determined using a threshold of less than 20%
      adsorption to the polypropylene surface. CONCLUSION: The ability to forecast the
      adsorption of a given compound to a polypropylene container with urine and CSF
      offers an effective means for screening potential issues and identifying when
      additional testing and corrective measures may need to be applied.

PMID- 21083274
TI  - Conventional and alternative matrices for driving under the influence of
      cannabis: recent progress and remaining challenges.
AB  - In the past decade much research concerning the impact of cannabis use on road
      safety has been conducted. More specifically, studies on effects of cannabis
      smoking on driving performance, as well as epidemiological studies and cannabis
      detection techniques have been published. As a result, several countries have
      adopted driving under the influence of drugs (DUID) legislations, with varying
      approaches worldwide. A wide variety of bodily fluids have been utilized to
      determine the presence of cannabis. Urine and blood are the most widely used
      matrices for DUID legislations. However, more and more publications focus on the
      usability of oral fluid testing for this purpose. Each matrix provides different
      information about time and extent of use and likelihood of impairment. This
      review will focus on the practical aspects of implying a DUID legislation. The
      pros and cons of the different biological matrices used for Delta(9)
      tetrahydrocannabinol screening and quantification will be discussed. In addition,
      a literature overview concerning (roadside) cannabinoid detection, as well as
      laboratory confirmation techniques is given. Finally, we will discuss important
      issues influencing interpretation of these data, such as oral fluid collection,
      choice of cut-offs, stability and proficiency testing.

PMID- 21083275
TI  - Determination of lung deposition following inhalation of ciclesonide using
      different bioanalytical procedures.
AB  - Ciclesonide (Alvesco((r))) is an inhaled corticosteroid administered as a
      solution via a metered-dose inhaler, using hydrofluoroalkane HFA-134a as a
      propellant. Ciclesonide is inhaled as a prodrug, which is activated by pulmonary
      esterases to the pharmacologically active metabolite desisobutyryl-ciclesonide
      (des-CIC). Lung deposition is an important factor that contributes to the desired
      therapeutic effect of inhaled corticosteroid. More than 50% of the inhaled dose
      is deposited in the lung as demonstrated by scintigraphical methods after
      inhalation of ciclesonide. The swallowed drug does not contribute to the systemic
      circulation because of the low oral systemic bioavailability, which is below 1%
      for ciclesonide and des-CIC. Due to the negligible oral bioavailability the
      pharmacokinetic parameters following inhalation are a surrogate for lung
      deposition. The pulmonary bioavailability was more than 60% as assessed for des
      CIC in pharmacokinetic studies using HPLC-MS/MS detection as bioanalytical
      method. Pharmacokinetics in asthmatic patients and healthy subjects are similar.

PMID- 21083276
TI  - Gradient counterflow electrophoresis methods for bioanalysis.
AB  - CE has evolved as one of the most efficient separation techniques for a wide
      range of analytes, from small molecules to large proteins. Modern microdevices
      facilitate integration of multiple sample-handling steps, from preparation to
      separation and detection, and often rely on CE for separations. However, CE
      frequently requires complex geometries for performing sample injections and
      maintaining zone profiles across long separation lengths in microdevices. Two
      novel methods for performing electrophoretic separations, gradient elution moving
      boundary electrophoresis (GEMBE) and gradient elution isotachophoresis (GEITP),
      have been developed to simplify microcolumn operations. Both techniques use
      variable hydrodynamic counterflow and continuous sample injection to perform
      analyses in short, simple microcolumns. These properties result in instruments
      and microdevices that have minimal 'real-world' interfaces and reduced
      footprints. Additionally, GEITP is a rapid enrichment technique that addresses
      sensitivity issues in CE and microchips.

PMID- 21083277
TI  - Metabolomics: an integral technique in systems biology.
AB  - Metabolomics is the unbiased identification and state-specific quantification of
      all metabolites in a cell, tissue or whole organism, and has developed rapidly
      into one of the cornerstones of postgenomic techniques for the quantitative
      analysis of molecular phenotypes. These large-scale analyses of metabolites are
      intimately bound to advancements in MS technologies and have emerged in parallel
      with the development of novel mass analyzers and hyphenated techniques, as well
      as with the combination of different techniques to cope with the physicochemical
      diversity of a metabolome. This review gives a brief description of the
      development and applications of these technologies in biochemistry and systems
      biology, and discusses their significance in the postgenomic era. Especially, the
      systematic relation between high-throughput metabolomic data and their
      interpretation with respect to the underlying biochemical regulatory network is
      discussed.

PMID- 21083279
TI  - Selectivity of ligand-binding assays in relationship to the measurement of
      biologics: how much does it matter?

PMID- 21083281
TI  - Interview with Janet Woodcock.
AB  - Dr Janet Woodcock is the Director of the US FDA's Center for Drug Evaluation and
      Research. Dr Woodcock has held various positions within the FDA's Office of the
      Commissioner from October 2003 until 1 April 2008, as Deputy Commissioner and
      Chief Medical Officer, Deputy Commissioner for Operations and Chief Operating
      Officer and Director of the Critical Path Programs. She oversaw scientific and
      medical regulatory operations for the FDA. Dr Woodcock served as Director of the
      Center for Drug Evaluation and Research at the FDA from 1994 to 2005. She
      previously served in other positions at the FDA, including Director of the Office
      of Therapeutics Research and Review and Acting Deputy Director of the Center for
      Biologics Evaluation and Research. Dr Woodcock received her MD from Northwestern
      Medical School (IL, USA), and completed further training and held teaching
      appointments at the Pennsylvania State University (PA, USA) and the University of
      California in San Francisco (CA, USA). She joined the FDA in 1986.

PMID- 21083282
TI  - Immunogenicity: prediction, detection and effective assay development.

PMID- 21083283
TI  - Bioanalysis: Young Investigator 2010.

PMID- 21083284
TI  - Fast and sensitive LC-MS/MS assay for quantification of nortriptyline and its
      active metabolites E- and Z-10-hydroxynortriptyline in human plasma.
AB  - BACKGROUND: A fast and sensitive validated assay for nortriptyline, E-10
      hydroxynortriptyline and Z-10-hydroxynortriptyline in plasma following a single
      oral dose of nortriptyline 25 mg was needed to support a clinical study. RESULTS:
      Plasma samples were prepared by protein precipitation, separated on a C18 column
      with a mobile phase consisting of 0.1% formic acid in an acetonitrile gradient
      over 6 min and detected by ESI in the positive mode and MS/MS. Mean recoveries of
      at least 90% were achieved. The LLOQ was 0.2 ng/ml for nortriptyline and 0.5
      ng/ml for the metabolites. The standard curve was linear within LLOQ to 40 ng/ml
      (r(2) >= 0.997), precision was under 7.1% coefficient of variance (<16% at LLOQ)
      and accuracy was 92-114%. CONCLUSION: A fast and sensitive assay for
      nortriptyline, E- and Z-10-hydroxynortriptyline in plasma was developed and
      validated. It has been applied successfully to a clinical study.

PMID- 21083285
TI  - Characterization and development of a Luminex((r))-based assay for the detection
      of human IL-23.
AB  - BACKGROUND: IL-23 is a cytokine produced by dendritic cells, T-cells and
      macrophages that plays a critical regulatory role in the inflammatory and
      autoimmune responses. We describe the development and preclinical validation of a
      highly sensitive Luminex((r)) assay specific to IL-23 that is suitable for its
      measurement in support of early-phase clinical trials. RESULTS: Intra-assay
      precision for the BioSourceTM ELISA was under 12.3%, and under 5.2% for the
      eBioscience((r)) ELISA. In comparison, the Luminex assays provided an intra-assay
      precision under 6.2%. The measured inter-assay precision was less than 15.6% for
      the BioSource ELISA, under 33% for the eBioscience and less than 10% for the
      Luminex assays. CONCLUSIONS: The Luminex method described provides a way to
      measure IL-23 in clinical samples either as a single biomarker or as a panel of
      biomarkers. The assay should prove useful to scientists and clinicians
      investigating the biology of IL-23 and to those needing to monitor changes in IL
      23 as part of a clinical study.

PMID- 21083286
TI  - Challenges in urine bioanalytical assays: overcoming nonspecific binding.
AB  - Dr Allena Ji is the Director of Bioanalytical Services, XenoBiotic Laboratories,
      Inc., NJ, USA. She has worked in the bioanalytical field for many years and
      accumulated rich experience in LC-MS/MS method development, method validation and
      sample analysis under GLP compliance in large pharmaceutical company and contract
      laboratory settings. In the past 10 years, Allena worked at Pfizer (Legacy of
      Wyeth) and investigated many small-molecule drug candidates for their nonspecific
      binding in urine assays. Nonspecific binding of compounds results in a severe
      underestimation of the compounds' concentrations and poor precision and accuracy
      in urine bioanalytical assays. To overcome nonspecific binding in urine assays,
      Allena and her colleagues developed a series of practical approaches for urine
      method development. By adding an appropriate anti-adsorptive agent at its optimum
      concentration to the urine collection containers, the nonspecific binding can be
      blocked. Urine assays have much higher hurdles than plasma assays due to
      nonspecific binding and variability of urine pH, salt concentration, volume and
      solubility of drug(s) in urine. A simple and systematic approach for urine method
      development is emphasized in this paper. Nonspecific binding is a very serious
      issue in bioanalytical urine assays where a compound(s) adsorbs to the container
      wall. The adsorption happens frequently in urine assays because urine lacks
      proteins and lipids that can bind to the analytes or solubilize lipophilic
      analytes. Therefore, urine bioanalytical assays tend to suffer from analyte
      losses more often than plasma assays. In the past decade, there have been many
      methods described to overcome nonspecific adsorption in urine assays based on
      individual analyte characteristics. However, a common and simple method
      development approach for various analytes has not been discussed and summarized.
      In this article we demonstrate, discuss and summarize a common approach to urine
      method development with a focus on overcoming adsorption issues. The advantages
      and limitations of commonly used anti-adsorptive agents, such as bovine serum
      albumin, zwitterionic detergents such as CHAPS, sodium dodecyl benzene sulfonate,
      beta-cyclodextrin, Tween 80 and Tween 20 are discussed.

PMID- 21083287
TI  - Bioanalytical method requirements and statistical considerations in incurred
      sample reanalysis for macromolecules.
AB  - BACKGROUND: Incurred sample reanalysis (ISR) is the most recent in-study
      validation parameter that regulatory agencies have mandated to ensure
      reproducibility of bioanalytical methods supporting pharmacokinetic/toxicokinetic
      and clinical studies. The present analysis describes five representative case
      studies for macromolecule therapeutics. METHOD: Single ISR acceptance criteria
      (within 30% of the averaged or original concentration) and a modified Bland
      Altman (BA) approach were used to assess accuracy and precision of ISR results.
      General concordance between the two criteria was examined using simulation
      studies. RESULTS: All five methods met the ISR criteria. The results indicated
      that thorough method development and prestudy validation were prerequisites for a
      successful ISR. The overall agreement between the original and reanalyzed results
      as determined by BA was within 20%. Simulation studies indicated that concordance
      between the ISR criteria and BA was observed in 95% of the cases. Dilution
      factors had no significant impact on the ISR, even for C(max) samples where 1:100
      or higher dilutions were used. CONCLUSION: The current ISR acceptance criteria
      for macromolecules was scientifically and statistically meaningful for methods
      with a total error of 25% or less.

PMID- 21083288
TI  - Absolute quantification of a therapeutic domain antibody using ultra-performance
      liquid chromatography-mass spectrometry and immunoassay.
AB  - BACKGROUND: Domain antibodies (dAbs; ~10-15 kDa) are made up of the variable
      heavy chain or the variable light chain of the antibody structure, and retain
      binding capability. dAbs have proved difficult to detect in plasma using
      immunoassay without specific antibodies raised against the dAb. RESULTS: A
      sensitive and selective UPLC-MS/MS method for the absolute quantification of a
      dAb in monkey plasma was developed (range: 1 to 500 ng/ml) without the need for a
      specific capture antibody. This method was used to analyze pharmacokinetic
      studies early on in drug development. Furthermore, an immunoassay was developed
      and the pharmacokinetic samples were reanalyzed. CONCLUSION: The two assays show
      good correlation (r(2) = 0.92), giving confidence in using either method for
      quantification of the dAb.

PMID- 21083289
TI  - Recent advances in clinical proteomics using mass spectrometry.
AB  - The ultimate objective of clinical proteomics is the successful discovery,
      validation and translation of biomarkers, together with new therapeutic targets
      into medical practices. New highly developed technologies in proteomics and their
      use in understanding tumor biology have significant clinical potential in the
      diagnosis, prognosis and treatment of disease. Areas such as MS, new labeling
      technologies and advancements in bioinformatics systems are now used to
      successfully detect disease-associated biomarkers together with therapeutic
      targets in complex biological specimens, including biofluids, cell lysates and
      tissue biopsies. Recent improvements in sample preparation (specifically focused
      on fractionation and enrichment) are enabling the analysis of low-abundance
      proteins together with many types of post-translational modifications. Targeted
      proteomic diagnostics will play a significant role in the development of
      personalized molecular medicine, a process that will be vital in modernizing
      healthcare structures.

PMID- 21083290
TI  - Development and validation of flow cytometry methods for pharmacodynamic clinical
      biomarkers.
AB  - Flow cytometry is a powerful analytical tool for the analysis of multiple
      biological parameters of individual cells or particles within heterogeneous cell
      populations. It has been widely used in biomedical research to perform
      immunophenotyping, cell counting and numerous cell function assessments, such as
      intracellular cytokine production, protein phosphorylation, cell proliferation
      and apoptosis. The implementation of standardized flow cytometry-based biomarker
      assays in clinical trials remains a challenge due to the limited stability of
      clinical specimens and the technical variations between instruments. To ensure
      data quality, it is crucial to develop robust assays for clinical applications.
      In this review, we summarize current practice in developing, validating and
      implementing flow cytometry assays to evaluate biomarkers in clinical research.

PMID- 21083292
TI  - Bioanalytical applications of capillary electrophoresis with laser-induced native
      fluorescence detection.
AB  - In this article we describe recent developments and applications of capillary
      electrophoresis (CE) coupled with laser-induced native fluorescence (LINF)
      detection in the analysis of biological, pharmaceutical and environmental
      samples. Compared with traditional UV absorbance detection used in CE, the LINF
      technique can greatly improve the concentration sensitivity of CE without the
      need for derivatization; the only requirement being that the analyte must have
      native fluorescence. Instrumentation and laser sources used in CE-LINF are
      summarized and specific applications of CE-LINF to small-biomolecule analysis,
      profiling of human biofluids, detection of native fluorescent peptides and
      proteins, single-cell analysis and the use of online sample preconcentration
      methods are also reviewed in detail.

PMID- 21083291
TI  - Bioanalytical solutions to acetonitrile shortages.
AB  - The acetonitrile shortage during 2008 to 2009 challenged bioanalytical scientists
      due to the ubiquitous role that acetonitrile plays in sample preparation and
      analysis. Replacement, reduction and reuse of acetonitrile were the core tenants
      behind each approach used to tackle the shortage. Sample preparation of
      biological matrices can be accomplished by protein precipitation using a variety
      of solvents; methanol is usually the best substitute for acetonitrile. The
      potential liabilities in using methanol can be handled with appropriate
      modifications. Often methanol is superior to acetonitrile for both protein
      precipitation and chromatography if phospholipid interference is a problem.
      Solvent consumption can be minimized by reducing column dimensions and particle
      size. Separations can be achieved at greatly reduced run times using sub-2-MUm
      and fused-core particle columns. Emerging technologies, such as desorption ESI,
      direct analysis in real time and laser diode thermal desorption, eliminate the
      need for chromatography and achieve significant solvent and time savings.
      Acetonitrile recyclers can purify HPLC waste for reuse.

PMID- 21083294
TI  - Global outsourcing.

PMID- 21083295
TI  - Bioanalysis in China.

PMID- 21083296
TI  - An evolutionary view of chromatography data systems used in bioanalysis.
AB  - This is a personal view of how chromatographic peak measurement and analyte
      quantification for bioanalysis have evolved from the manual methods of 1970 to
      the electronic working possible in 2010. In four decades there have been major
      changes from a simple chart recorder output (that was interpreted and quantified
      manually) through simple automation of peak measurement, calculation of standard
      curves and quality control values and instrument control to the networked
      chromatography data systems of today that are capable of interfacing with
      Laboratory Information Management Systems and other IT applications. The
      incorporation of electronic signatures to meet regulatory requirements offers a
      great opportunity for business improvement and electronic working.

PMID- 21083297
TI  - The historical role of gas chromatography in bioanalysis.

PMID- 21083299
TI  - Research spotlight: stereoselective analysis of drugs and metabolites by the
      Chromatographic and Electrophoretic Analysis Center group.

PMID- 21083300
TI  - Conference report: new analytical technologies for biological discovery.

PMID- 21083301
TI  - Conference report: Applied Pharmaceutical Analysis 2009 Conference.

PMID- 21083302
TI  - Determination of calcium in synovial fluid samples as an aid to diagnosing
      osteoarthritis.
AB  - BACKGROUND: Microscopic inorganic crystals are commonly observed in the synovial
      fluid of patients suffering from arthritic diseases. Basic calcium phosphate
      (BCP) crystals are known to occur quite commonly in the joint fluid of
      osteoarthritis (OA) patients and are insoluble at physiological pH. Current
      analysis of patient synovial fluid depends on light microscopy and staining with
      Alizarin Red-S. Both methods cannot identify crystals < 1um in size and are
      highly subjective. This article investigates the use of o-cresolphthalein
      complexone (OCP), a colorimetric reagent, to quantify calcium from crystals
      isolated from synovial fluid samples as a means of identifying the presence of
      BCP and, hence, improving the diagnosis of OA. RESULTS: Inorganic crystals were
      isolated following degradation of the biological sample matrix with
      hyaluronidase. 1-M HNO(3) was used for crystal dissociation into ions and the
      colorimetric response of OCP to calcium was measured in a basic environment of 2
      amino-2-methyl-1-propanol. The average calcium content in OA patient samples was
      up to 40% higher than in rheumatoid arthritis (RA) patient samples. RA samples
      were used as a comparison, because they are generally accepted to be crystal
      free. Within the OA group, higher levels of calcium were detected in three out of
      12 synovial fluid samples, which correlated with a significantly greater number
      of BCP crystals detected during microscopic examination. CONCLUSIONS: A simple
      method based on colorimetry for measurement of calcium content and
      semiquantification of BCP crystals in synovial fluid samples has been described.
      Sample pretreatment following addition of hyaluronidase proved to be effective in
      reducing viscosity and aiding the dissociation of BCP crystals in synovial fluid
      samples.

PMID- 21083303
TI  - Microextraction by packed sorbent for LC-MS/MS determination of drugs in whole
      blood samples.
AB  - BACKGROUND: Microextraction by packed sorbent (MEPS) is used as an online sample
      preparation method. The determination of local anesthetics lidocaine, ropivacaine
      and bupivacaine directly in human blood was performed using MEPS online with LC
      MS/MS. RESULTS: The range of the calibration curves in whole blood was 10-10000
      nmol/l. The lower limit of quantification was set to 10.0 nmol/l. The accuracy of
      the quality control samples ranged from 85 to 97%. The interday precision of the
      studied analytes was within the range 1-5%. The regression correlation
      coefficient (r(2)) was over 0.995 for all runs. The present method is rapid,
      reliable and robust and may be used for therapeutic drug monitoring of studied
      analytes in whole blood. CONCLUSION: This assay allows the analysis of drugs in
      human blood directly. Sample preparation is simple and automated. The assay
      reduced the handling time and the cost, and could handle small volumes of whole
      blood samples (25 ul).

PMID- 21083304
TI  - Study of valproic acid-induced endogenous and exogenous metabolite alterations
      using LC-MS-based metabolomics.
AB  - BACKGROUND: Valproic acid (VPA; an anticonvulsant drug) therapy is associated
      with hepatotoxicity as well as renal toxicity. An LC-MS-based metabolomics
      approach was undertaken in order to detect urinary VPA metabolites and to
      discover early biomarkers of the adverse effects induced by VPA. RESULTS: CD-1
      mice were either subcutaneously injected with 600-mg VPA/kg body weight or
      vehicle only, and urine samples were collected at 6, 12, 24 and 48 h
      postinjection. A metabolomics approach combined with principal component analysis
      was utilized to identify VPA-related metabolites and altered endogenous
      metabolites in urine. Some VPA metabolites indicated potential liver toxicity
      caused by VPA administration. Additionally, some altered endogenous metabolites
      suggested that renal function might be perturbed by VPA dosing. CONCLUSION: LC-MS
      based metabolomics is capable of rapidly profiling VPA drug metabolites and is a
      powerful tool for the discovery of potential early biomarkers related to
      perturbations in liver and kidney function.

PMID- 21083305
TI  - Tetracycline sensing using novel doxycycline derivatives immobilized on different
      surface plasmon resonance biosensor surfaces.
AB  - BACKGROUND: This article aims to explore novel doxycycline derivatives for
      analyzing low concentrations of tetracyclines in biological matrices and food in
      competitive assays. RESULTS: Surface plasmon resonance (SPR) was employed in an
      indirect competitive format using a bacterial tetracycline-dependent regulatory
      protein as receptor. Three doxycycline derivatives were synthesized and
      covalently bound to the surface of four different sensor chips. Parameters that
      influence the immobilization of the doxycycline derivatives and subsequent
      binding of the receptor protein were studied. CONCLUSION: The novel doxycycline
      derivatives were successfully used as competitors in an indirect SPR assay.

PMID- 21083306
TI  - Detection of prohibited substances in equestrian sport through direct injection
      of equine serum using micellar LC.
AB  - BACKGROUND: Detection of prohibited substances in equestrian sports typically
      involves time-consuming and tedious sample-preparation methods. Micellar LC (MLC)
      allows for direct injection of equine serum to detect prohibited NSAIDs. RESULTS:
      The method was linear over the range of standards examined, with recoveries of
      94.2-95.1% for phenylbutazone (12-18 ug/ml), and 83.9-88.7% and 87.9-105.0% for
      diclofenac and flunixin, respectively (0.1-1.2 ug/ml). The limit of detection was
      0.1 ug/ml for all compounds and the limit of quantitation was 0.2 ug/ml for
      phenylbutazone and 0.3 ug/ml for diclofenac and flunixin. CONCLUSION: The MLC
      method of direct equine serum injection was shown to be valid and simple for the
      quantitation of banned NSAIDs in equine serum.

PMID- 21083307
TI  - Systematic analytical validation of commercial kits for the determination of
      novel biomarkers for clinical drug development.
AB  - The use of biomarkers during clinical drug-development programs may expedite
      pipeline decision making by adding critical information about the pharmacological
      mechanism and efficacy of a potential therapeutic agent. Currently, advice for
      laboratorians conducting method development and analytical validation of
      biomarker methods is provided by published White Paper recommendations from
      industry thought leaders. The adaptation of commercial test kits to generate
      biomarker data to support regulated studies offers unique challenges and
      limitations. In this perspective, we address these issues, including factors to
      consider when identifying a kit manufacturer and adapting commercial test kits
      for use in regulated studies. We offer a logical and systematic approach for
      defining the extent of analytical validation needed for application of commercial
      kits based upon the intended use of the biomarker data.

PMID- 21083308
TI  - The future of diagnostic gene-expression microarrays: bridging the gap between
      bench and bedside.
AB  - During the last two decades, an increasing number of microarray studies have
      identified gene-expression profiles that link disease characteristics to patient
      outcome. However, despite improvements in technology and the clinical relevance
      of the identified profiles, only a handful of microarray tests are currently
      available for clinical use. So why have microarrays, regardless of the great
      application and success within a research setting, not yet been embraced for
      routine diagnostic use? Besides the strengths of microarray diagnostics, this
      perspective will outline the important challenges that need to be considered for
      successful translation of a gene profile into a routine diagnostic test. Finally,
      some new microarray technologies will be reviewed and an outlook for the future
      of diagnostic microarrays will be presented.

PMID- 21083309
TI  - Detection and quantitation of beta-blockers in plasma and urine.
AB  - beta-blockers are a class of antihypertensive drugs that are used for the
      management of cardiac arrhythmias, cardioprotection after myocardial infarction
      (heart attack) and hypertension. They have revolutionized the medical management
      of angina pectoris and are recommended as first-line agents by national and
      international guidelines. Although beta-blockers are still the cornerstone for
      the treatment of heart failure, some of the drugs in this category are prohibited
      in several sports requiring vehicle control and bodily movements as they reduce
      heart rate and tremors, and improve performance. As a result, urine analysis of
      beta-blockers is mandatory in doping control and toxicological screening. The
      determination of plasma levels of beta-blockers helps to ensure noncompliance in
      patients with persistent hypertonia to confirm the diagnosis of beta-blocker
      poisoning and for therapeutic drug monitoring. This review provides a
      comprehensive account of various analytical methods developed for detection and
      quantitation of beta-blockers in plasma and urine.

PMID- 21083310
TI  - Mass spectrometry imaging of pharmacological compounds in tissue sections.
AB  - The use of MS imaging (MSI) to resolve the spatial and pharmacodynamic
      distributions of compounds in tissues is emerging as a powerful tool for
      pharmacological research. Unlike established imaging techniques, only limited a
      priori knowledge is required and no extensive manipulation (e.g., radiolabeling)
      of drugs is necessary prior to dosing. MS provides highly multiplexed detection,
      making it possible to identify compounds, their metabolites and other changes in
      biomolecular abundances directly off tissue sections in a single pass. This can
      be employed to obtain near cellular, or potentially subcellular, resolution
      images. Consideration of technical limitations that affect the process is
      required, from sample preparation through to analyte ionization and detection.
      The techniques have only recently been adapted for imaging and novel variations
      to the established MSI methodologies will further enhance the application of MSI
      for pharmacological research.

PMID- 21083311
TI  - Methods for the discovery of low-abundance biomarkers for urinary bladder cancer
      in biological fluids.
AB  - For the study of bladder cancer and the identification of respective tumor
      markers, blood and, in particular, urine constitute suitable sources of
      biological material, while both harboring their specific challenges for analytics
      concerning low-abundance biomarkers. Dissolved proteins and nucleic acids as well
      as cells and cell-bound molecules can be the analytes. In urine, exfoliated
      bladder tumor cells have to be identified and in blood, circulating tumor cells
      have to be detected among huge amounts of other cells. For the detection of both
      low-abundance cells and molecules, their specific enrichment prior to analysis is
      advantageous or even necessary. Adapted methods for the analysis of proteomes and
      subproteomes by 2D-gel electrophoresis, multidimensional chromatography and
      antibody arrays are discussed. Analysis of nucleic acid-based markers exploits
      the high amplification power of PCR and modified PCR combined with previous
      (subtransciptomes) or subsequent (microarray) enrichment to sensitively and
      specifically detect markers. DNA mutations, DNA-methylation status and apoptotic
      DNA fragments, as well as levels of ribonucleic acids including microRNAs, can be
      analyzed by means of these methods. Finally, the challenge of identifying
      circulating tumor cells and assigning them to their original tissue is critically
      discussed.

PMID- 21083312
TI  - Bioanalysis of meningococcal vaccines.
AB  - Meningococcal meningitis is feared because of the rapid onset of severe disease
      from mild symptoms and, therefore, is an important target for vaccine research.
      Five serogroups, defined by the structures of their capsular polysaccharides, are
      responsible for the vast majority of disease. Protection against four of these
      five serogroups can be obtained with polysaccharide or glycoconjugate vaccines,
      in which fragments of the capsular polysaccharides attached to a carrier protein
      generate anticarbohydrate immune responses, whilst protection against group B
      disease requires protein immunogens, often presented in vesicles containing outer
      membrane proteins. Glycoconjugate vaccines are now an established technology, but
      outer-membrane protein vaccines are still under development and present
      significant challenges. This review discusses physicochemical approaches to the
      characterization and quality control of these vaccines, as well as highlighting
      the problems and differences in vaccine design required for protection against
      different serogroups of the same species of pathogen.

PMID- 21083314
TI  - Bioanalytical applications in microfluidics.

PMID- 21083315
TI  - The potential and application of microfluidic paper-based separation devices.

PMID- 21083316
TI  - Translational research needed in microfluidics and immunoaffinity separations.

PMID- 21083317
TI  - Jell-O((r)) microfluidics and synthetic biology: combining science outreach with
      basic research.

PMID- 21083319
TI  - Summary of the Eleventh Annual University of Wisconsin Land O'Lakes Bioanalytical
      Conference.

PMID- 21083320
TI  - Micro open-sandwich ELISA to rapidly evaluate thyroid hormone concentration from
      serum samples.
AB  - BACKGROUND: Thyroxine (T4) is the most commonly measured thyroid hormone for the
      diagnosis of thyroid function. To elucidate a rapid and sensitive assay for T4,
      we made a microfluidics-based noncompetitive immunodetection chip system using
      anti-T4 antibody fragments obtained from a phage display library. RESULTS: Based
      on the open-sandwich ELISA principle that detects antigen-dependency of the
      interaction between the two antibody variable regions V(H) and V(L), we could
      detect less than 1 ng/ml of T4. The assay was also successfully applied to
      evaluate total T4 concentration in the serum of healthy individuals. CONCLUSION:
      This would be the first micro open-sandwich ELISA constructed with antibody
      fragments directly selected from immunized mice. The system will be applied to
      the sensitive detection of many diagnostic markers.

PMID- 21083321
TI  - Transfection of molecular beacons in microchannels for single-cell gene
      expression analysis.
AB  - BACKGROUND: Efficient transfection of molecular beacons has to be performed in
      the microscale in order to fully utilize the potential of molecular beacons and
      microfluidics for studying the real-time gene-expression dynamics in living
      cells. Nevertheless, there has been relatively little study on transfection of
      molecular beacons in microfluidic channels. RESULTS: In this work, the
      differences between transfection in conventional cell culture systems and in
      microfluidic cell culture systems were investigated systematically with a
      combination of computational and experimental methods. Comparison between a no
      flow microchannel and a 96-well plate revealed that the scale-dependence of
      reaction-diffusion kinetics contributes to the reduced transfection efficiency in
      the no-flow microchannel. Study on transfection in the microfluidic system under
      flow conditions suggested that the fluid flow enhances mass transfer, while the
      fluid shear stress can reduce the transfection efficiency. CONCLUSION: The
      results of this study will provide useful guidelines in optimizing molecular
      beacon transfection efficiency in microfluidic systems for studying gene
      expression dynamics in living cells.

PMID- 21083322
TI  - Large-volume centrifugal microfluidic device for blood plasma separation.
AB  - BACKGROUND: Microfluidic-based systems are ideal for handling small microliter
      volumes of samples and reagents, but 'real-world' or clinical samples for
      bioanalysis are often on the milliliter scale. We aimed to develop and validate a
      large-volume centrifugal or compact disc-based device for blood plasma
      separation, capable of processing 2 ml undiluted blood samples. RESULTS: This
      automated blood sample preparation device was shown to yield high purity plasma
      in less than half the time of commercial plasma preparation tubes, while enabling
      integration with downstream analysis and detection steps. CONCLUSION: This
      article draws upon a novel large-volume device to further illustrate the
      challenges in combining microfluidics structures with large-volume samples and
      the implications for sample-driven microfluidics systems.

PMID- 21083323
TI  - Application of the GyrolabTM platform to ligand-binding assays: a user's
      perspective.
AB  - In many areas of drug discovery and development, scientists are in a constant
      search for methods and platforms to reduce assay time and cost. The GyrolabTM
      microfluidics platform that we describe here promises to deliver faster ligand
      binding assays with lower reagent and sample consumption, while maintaining good
      accuracy and precision. Due to its limited track record, we evaluated its
      performance on assays currently used to support pharmacokinetic and
      immunogenicity studies, and detection of host cell protein impurities in samples
      from biotechnology processes. This article summarizes our preliminary conclusions
      about the utility of the Gyrolab microfluidics platform from Gyros AB.

PMID- 21083324
TI  - Surface patterning strategies for microfluidic applications based on
      functionalized poly-p-xylylenes.
AB  - Microfluidic systems require precise surface modification in order to tailor the
      interfacial properties. For instance, in lab-on-a-chip research, defined surface
      chemistry is key to minimizing contamination and to increasing signal-to-noise
      ratios for bioconjugation schemes. Device efficiency and analytical output can
      also be maximized with devices that have defined surfaces. Similarly, minimizing
      biofouling is also crucial to suppress background noise and ensure device
      functions. Once defined, surface properties have been engineered,
      microstructuring of surfaces can provide defined microenvironments for cell-based
      culture systems. In this report, we highlight the use of functionalized poly-p
      xylylenes for surface modification with a specific focus on microfluidic systems.
      Functionalized poly-p-xylylenes constitute a versatile group of reactive coatings
      that can provide a defined chemical makeup of substrate surfaces irrespective of
      underlying bulk material properties. Recent advances using reactive coatings for
      surface modification of microfluidics are introduced, including use as nonfouling
      coatings, fabrication of patterned surfaces, functionalization of previously
      assembled devices, as well as device-bonding applications.

PMID- 21083325
TI  - Application of microfluidic technology to pancreatic islet research: first decade
      of endeavor.
AB  - beta-cells respond to blood glucose by secreting insulin to maintain glucose
      homeostasis. Perifusion enables manipulation of biological and chemical cues in
      elucidating the mechanisms of beta-cell physiology. Recently, microfluidic
      devices made of polydimethylsiloxane and Borofloat glass have been developed as
      miniaturized perifusion setups and demonstrated distinct advantages over
      conventional techniques in resolving rapid secretory and metabolic waveforms
      intrinsic to beta-cells. In order to enhance sensing and monitoring capabilities,
      these devices have been integrated with analytical tools to increase assay
      throughput. The spatio-temporal resolutions of these analyses have been improved
      through enhanced flow control, valves and compartmentalization. For the first
      time, this review provides an overview of current devices used in islet studies
      and analyzes their strengths and experimental suitability. To realize the
      potential of microfluidic islet applications, it is essential to bridge the gap
      in design and application between engineers and biologists through the creation
      of standardized bioassays and user-friendly interfaces.

PMID- 21083326
TI  - Toward point-of-care microchip profiling of proteins.
AB  - Profiling of protein biomarkers is powerful for the analysis of complex proteomes
      altered during the progression of diseases. Lab-on-a-chip technologies can
      potentially provide the throughput and efficiency required for point-of-care and
      clinical applications. While initial studies utilized 1D microchip separation
      techniques, researchers have recently developed novel 2D microchip separation
      platforms with the ability to profile thousands of proteins more effectively.
      Despite advancements in lab-on-a-chip technologies, very few reports have
      demonstrated a point-of-care microchip-based profiling of proteins. In this
      review, recent progress in 1D and 2D microchip profiling of protein mixtures of a
      biological sample with potential point-of-care applications are discussed. A
      selection of recent microchip immunoassay-based techniques is also highlighted.

PMID- 21083327
TI  - Ongoing development of image cytometers.
AB  - Image cytometry is a method for quantitative cellular analysis using images
      generally captured on slides or microfabricated chips. The flowless nature of
      data acquisition in image cytometry allows the use of value components, such as
      light-emitting diode excitation sources or low-cost charge-coupled device
      detectors. Unlike flow cytometry, the stationary cellular samples can be exposed
      to lower-intensity light and utilize less sensitive detectors with higher
      exposure times. Images are acquired and data is processed using recognition
      software to identify, count and analyze cells. Current image cytometers cannot
      replicate the quality of the data from flow cytometers or fluorescence
      microscopes with full functionality and performance components. Yet, the
      production of inexpensive image cytometers for use in small laboratories and
      clinics has made a compelling argument. The addition of fluorescence detection to
      the new generation of image cytometers has opened the field to a broader range of
      applications. This article will review the technical aspects and application of
      image cytometers, the recent progress in the field and available commercial
      devices.

PMID- 21083330
TI  - A glowing future for dried blood spot sampling.

PMID- 21083328
TI  - A novel LC-MS approach for the detection of metabolites in DMPK studies.
AB  - BACKGROUND: The profiling and quantification of drug metabolites in discovery and
      development bioanalysis studies is playing an increasingly important role in
      early candidate selection. Using a conventional tandem quadrupole mass
      spectrometer this activity normally requires several analytical runs to acquire
      the necessary analytical data. RESULTS: In this article we present the use of a
      new tandem quadrupole mass spectrometer equipped with a novel collision cell
      design, which allows the rapid switching between multiple reaction monitoring and
      full-scan MS mode. This approach allowed for the collection of multiple reaction
      monitoring data and full-scan data with no loss in sensitivity, with analysis
      times in the 1-2 min range. CONCLUSION: A modified approach of using the multiple
      reaction monitoring data to trigger the acquisition of full scan MS/MS data is
      described, where the data is collected on the trailing edge of the LC-MS peak,
      thus improving data quality and throughput.

PMID- 21083331
TI  - Bioanalysis: the best of 2009.

PMID- 21083332
TI  - Does validation stagnate innovation?

PMID- 21083334
TI  - Conference Report: DIA/PhRMA workshop on DBS sampling in the pharmaceutical
      industry: methodology, implementation & best practices.

PMID- 21083336
TI  - DBS: a UK (MHRA) regulatory perspective.

PMID- 21083337
TI  - Exploring the feasibility of using the DBS technique for metabolite
      radioprofiling.
AB  - BACKGROUND: The dried blood spots (DBS) technique has been actively evaluated as
      plasma replacement for monitoring drug exposure to support drug development in
      preclinical/clinical pharmacokinetic and toxicokinetic studies. Plasma samples
      from some of these studies are typically used for metabolite profiling and
      identification and for determination of disproportionate metabolites between
      safety species and humans to address metabolites in safety testing issues. The
      objectives of this study were to explore the feasibility of using the DBS
      technique for a metabolism study and to compare metabolite radioprofiles between
      DBS, plasma and whole blood samples. RESULTS: The radioactivity extraction
      recovery in DBS samples was similar or better than that in plasma or whole blood.
      The metabolite radioprofiles in AUC pooled DBS samples using FTA((r)) and
      FTA((r)) Elute cards were comparable to those in AUC pooled plasma and whole
      blood. CONCLUSION: It is feasible to use DBS as an alternative matrix to plasma
      for in vivo metabolite radioprofiling studies for SA-1.

PMID- 21083338
TI  - Study to assess the effect of age of control human and animal blood on its
      suitability for use in quantitative bioanalytical DBS methods.
AB  - BACKGROUND: A study was performed to evaluate the suitability of stored EDTA
      treated control whole blood for use in the preparation of calibration standards
      and quality control samples for quantitative bioanalytical methods employing
      dried blood spot (DBS) samples to support pharmaceutical exposure studies.
      RESULTS: It has been demonstrated that a storage time of 14 days for control
      human and animal blood is suitable for producing quantitative analytical results
      within internationally recognised acceptance criteria for two analytes.
      Furthermore, blood hemolysis and chill-thaw cycles have been evaluated and shown
      not to affect bioanalytical results notably. Aggressive mixing techniques can
      result in rat blood coagulation; however, this does not occur with other species
      tested and can be affected by the method of blood collection. CONCLUSION: Control
      whole blood handled and stored using the recommendations generated from this
      study will not notably affect quantitative bioanalytical results when used for
      the preparation of calibration standards and quality control samples for DBS
      assays. It was demonstrated that control human and animal blood can be stored for
      periods long enough to effectively eliminate wastage.

PMID- 21083339
TI  - The effect of hematocrit on assay bias when using DBS samples for the
      quantitative bioanalysis of drugs.
AB  - BACKGROUND: As hematocrit levels are known to vary between individuals and with
      disease state, its effect on the physical characteristics of dried blood spot
      (DBS) samples and on the accurate quantification of analytes within these samples
      is examined. RESULTS: The area of DBS samples decreases with increasing
      hematocrit levels in a linear manner on the three cellulose paper substrates
      tested. Furthermore, a bias was observed in the concentrations of two analytes
      determined in DBS samples at different hematocrits, which in some cases exceeded
      acceptable values, particularly for hematocrits outside normal values.
      CONCLUSION: If it is expected that the hematocrit of study samples will vary from
      values considered normal, then its effect on the quantitative determination of an
      analyte in DBS samples should be investigated as part of the method development
      and validation. If an unacceptable effect is observed, then this will need to be
      addressed, by modification of the analytical method, or the inclusion of quality
      control samples at different hematocrit levels to show control of the assay.

PMID- 21083340
TI  - Performance properties of filter paper devices for whole blood collection.
AB  - BACKGROUND: The Newborn Screening Quality Assurance Program at the Centers for
      Disease Control and Prevention assesses the adherence to established performance
      standards of manufactured lots of whole blood filter paper collection devices
      that are registered by the US FDA. We examined 26 newborn screening analytes
      measured from blood applied to filter papers from two FDA-cleared sources,
      Whatman((r)) Grade 903 and Ahlstrom Grade 226. The dried blood spots contained
      analytes at both single levels and dose-response series. RESULTS: We observed
      overlap at one standard deviation for each analyte, with no more than 4-5%
      difference between the papers. CONCLUSION: The data demonstrated similarities of
      analyte recovery between the papers, indicating comparability of the devices for
      newborn screening and other applications.

PMID- 21083341
TI  - Evaluating and defining sample preparation procedures for DBS LC-MS/MS assays.
AB  - BACKGROUND: A defined approach to develop and validate an LC-MS/MS assay using
      dried blood spot (DBS) samples is of great interest to many scientists who are
      adopting this technology. We have evaluated three distinct sample preparation
      procedures of DBS samples for LC-MS/MS assay development. RESULTS: A new term
      'elution efficiency' is introduced to evaluate the effectiveness of eluting
      compounds from the DBS cards into the liquid phase. Three different types of DBS
      cards were studied as part of the sample preparation procedures. A DBS LC-MS/MS
      method was developed, qualified and then applied to a toxicokinetics study.
      CONCLUSION: Organic extraction and protein precipitation resulted in significant
      ion suppression and/or enhancement for FTA((r)) Classic or FTA((r)) Elute cards.
      Liquid-liquid extraction produced the least ion suppression/enhancement. Both
      protein precipitation and liquid-liquid extraction effectively eluted the probe
      compound from the DBS cards under the conditions tested. However, organic
      extraction by pure solvents resulted in low elution efficiency.

PMID- 21083342
TI  - DBS sampling can be used to stabilize prodrugs in drug discovery rodent studies
      without the addition of esterase inhibitors.
AB  - BACKGROUND: Prodrugs that exhibit ex vivo instability owing to high levels of
      esterases in rodent blood, plasma and serum present challenges in the accurate
      determination of drug exposure in samples from pharmacokinetic,
      pharmacokinetic/pharmacodynamic, efficacy and toxicology studies in drug
      discovery. Ensuring the stability of analytes in sample collection, handling,
      analysis and storage must be established for program progression. Current
      protocols for the stabilization of prodrugs include the immediate quenching of
      whole blood with acetonitrile or methanol to stop enzyme activity, or the
      addition of an esterase inhibitor such as phenylmethanesulfonyl fluoride to the
      blood collection tubes before serum or plasma is generated. Dried blood spots
      (DBS) sampling may offer an alternative prodrug stabilization method for sample
      collection and storage from rodent studies in drug discovery. RESULTS: Two
      different prodrugs of the same parent compound that were known to exhibit ex vivo
      instability in rodent blood were selected for the evaluation of DBS for analyte
      stabilization. Each prodrug was spiked separately into fresh rat EDTA whole blood
      and prepared three ways: from liquid whole blood, prepared and analyzed as
      lysate; from whole blood spotted onto Whatman 903((r)) Protein Saver untreated
      cards (903 cards); and from whole blood spotted onto Whatman FTA((r)) Elute Micro
      treated cards, currently known as DMPK-B cards (FTA cards). Samples were
      extracted by filtration-assisted protein precipitation at 0, 2, 5 and 24 h and 4,
      7, 14 and 21 days after spiking and analyzed by UHPLC-MS/MS. CONCLUSIONS: For
      these two prodrugs, stability on DBS cards was observed in rat EDTA whole blood
      for at least 21 days at room temperature as determined by loss of prodrug and
      appearance of parent. The Whatman FTA Elute cards, treated with reagents that
      lyse cells, did not offer more stability for the investigated compounds than the
      Whatman 903 Protein Saver untreated cards.

PMID- 21083343
TI  - Determination of mycophenolic acid and its phenyl glucuronide in human plasma,
      ultrafiltrate, blood, DBS and dried plasma spots.
AB  - BACKGROUND: Analysis of mycophenolic acid (MPA), the active form of the
      immunosuppressive drug mycophenolate mofetil, and its glucuronide metabolite MPAG
      is required for therapeutic monitoring and postmarketing clinical studies. Dried
      blood spots (DBS) and dried plasma spots (DPS) could be alternatives to
      conventional assays for small-volume sampling and easy shipment. RESULTS: A LC
      MS/MS method with online SPE was established using stable isotope labeled
      analytes as internal standards. The quantitation limits were set at 0.1 and 1
      ug/ml, for total MPA and MPAG, respectively, in plasma, blood, DBS and DPS, but
      100-fold lower for free MPA in ultrafiltrate. Ahlstrom 226 or Whatman FTA((r))
      DMPK-B cards were well suited for DBS and DPS analyses. CONCLUSION: MPA and MPAG
      were analyzed in human plasma and blood either as liquid or dried on cards with
      similar assay quality. Care should be taken to avoid back-conversion of an
      instable acyl glucuronide metabolite to MPA.

PMID- 21083344
TI  - Human DBS sampling with LC-MS/MS for enantioselective determination of metoprolol
      and its metabolite O-desmethyl metoprolol.
AB  - BACKGROUND: The dried blood spots (DBS) sampling technique has been gaining wide
      interest in preclinical and clinical studies due to its inherent advantages.
      However, the impact of DBS sampling on chiral compounds in terms of stability and
      detection sensitivity has not been studied yet. RESULTS: A high-throughput,
      sensitive and enantioselective LC-MS/MS-based bioanalytical method was developed
      and validated for the simultaneous determination of individual enantiomers of
      metoprolol and its metabolite O-desmethylmetoprolol (O-DMM)in human whole blood
      using the DBS sampling technique. CONCLUSIONS: The developed DBS LC-MS/MS assay
      has a run time of 3 min, shorter than all previous methods while achieving
      complete baseline separation of enantiomeric metoprolol and O-DMM. This study
      demonstrates the applicability of DBS for chiral molecules analysis.

PMID- 21083345
TI  - Assessment of DBS technology for the detection of therapeutic antibodies.
AB  - BACKGROUND: Quantitating levels of therapeutic proteins in serum or plasma is
      critical for determining exposure levels and establishing pharmacokinetic
      parameters. Traditionally, whole blood is not used, mostly due to its inability
      to be frozen and potential issues with assay interference. To investigate the
      ability to reproducibly quantitate therapeutic antibodies present in dried blood
      spots (DBS) compared with a typical serum sample-based method, we used ELISA and
      electrochemiluminescence immunoassays to measure therapeutic drug levels present
      in DBS samples. RESULTS: Measurements of antibody therapeutics in DBS were
      reproducible, yielding methods that are precise, accurate and met expected
      sensitivity requirements compared with plasma-based methods. CONCLUSIONS: DBS are
      a viable alternative to the use of conventional serum or plasma samples for
      quantitative therapeutic antibody measures.

PMID- 21083347
TI  - Impact of various factors on radioactivity distribution in different DBS papers.
AB  - BACKGROUND: Dried blood spot (DBS) sampling could potentially become the
      preferred blood collection technique in toxicological and clinical studies.
      Autoradiography was performed to study compound distribution within a dbs under
      different conditions using five papers, 31ETF, Grade 226, 903((r)), FTA((r)) and
      FTA((r)) Elute. RESULTS: The results showed an uneven distribution in all papers
      with common distribution patterns regardless of compounds: decreased
      concentrations along the edge, the volcano effect in the middle and the speckle
      pattern in the center. Treated papers were more readily influenced by
      environmental factors. CONCLUSION: Autoradiography enables visualization of a
      compound's distribution and can guide bioanalytical assay development by allowing
      convenient evaluation of factors, such as choice of paper, spotting volume, punch
      size, punch location, temperature and humidity.

PMID- 21083346
TI  - Application of DBS for quantitative assessment of the peptide Exendin-4;
      comparison of plasma and DBS method by UHPLC-MS/MS.
AB  - BACKGROUND: An investigation was performed in order to establish if dried blood
      spots (DBS) could be applied to the quantitation of biopharmaceuticals in
      biological matrices and perform equivalently in terms of accuracy, precision and
      stability to traditional plasma methods. RESULTS: A method was successfully
      validated for the peptide Exendin-4 (39 amino acids in length) utilizing DBS
      technology. The validated DBS method resulted in a more sensitive and simplistic
      method than an existing monkey plasma method and required tenfold less sample
      volume. The final DBS method resulted in a 10-2000-ng/ml linear calibration range
      using approximately 5 ul of dried blood, compared with the plasma method in which
      150 ul of plasma coupled with SPE sample preparation resulted in a 20-2000-ng/ml
      linear calibration range. Although not needed for DBS, SPE was required for the
      plasma method to reduce endogenous matrix interferences and achieve desired LLOQ.
      Matrix stability was also enhanced by the implementation of the DBS platform when
      compared with either plasma or whole blood. CONCLUSION: DBS technology can be
      utilized for the quantitation of biopharmaceuticals and offer advantages over
      traditional plasma-based methods.

PMID- 21083348
TI  - Utilization of DBS within drug discovery: development of a serial microsampling
      pharmacokinetic study in mice.
AB  - BACKGROUND: Dried blood spots (DBS) are rapidly gaining a foothold in the
      pharmaceutical industry. However, applications in exploratory drug discovery are
      limited mainly owing to method development time. The development of a generic DBS
      assay is presented with its application in serial microsampling from mice.
      RESULTS: A generic 'fit-for-purpose' assay was developed on FTA((r)) Elute, which
      allowed 90% of compounds tested to reach sensitivity levels of 1 ng/ml. A ten
      time point serial mouse pharmacokinetic study was conducted using 20-ul
      microsamples and DBS. Application of generic 'fit-for-purpose' approach did not
      compromise data delivery or quality. CONCLUSIONS: Serial microsampling and DBS in
      exploratory mouse pharmacokinetic has been shown to provide superior data quality
      when compared with traditional plasma-based composite studies.

PMID- 21083349
TI  - Application of the DBS methodology to a toxicokinetic study in rats and
      transferability of analysis between bioanalytical laboratories.
AB  - BACKGROUND: There are little published data on either the comparison of liquid
      blood and dried blood spots (DBS) analyses or the ability to generate comparable
      DBS data at different analytical laboratories. We assess the comparative results
      of samples stored as liquid blood and DBS. We also determine the transferability
      of DBS samples by comparing the analysis at two laboratories. RESULTS:
      Bioanalytical methods for the analysis of pioglitazone in DBS and liquid blood
      samples were validated to US FDA guidelines. Pharmacokinetic data generated from
      DBS and liquid blood samples demonstrated area under the time-concentration
      profile (0-24 h) values within 3% of each other and maximum plasma concentration
      values within 7% of each other. Comparing DBS sample results at different
      laboratories showed more than 99% of results agreeing within 20%. CONCLUSIONS:
      The results indicate that comparable concentration results are obtained from DBS
      and whole blood samples within the same laboratory, indicating that changing
      between the two matrices is viable. The comparable results of DBS samples
      analyzed at two laboratories using different analytical methodologies demonstrate
      that the technique is robust and transferable.

PMID- 21083350
TI  - Determination of naproxen using DBS: evaluation & pharmacokinetic comparison of
      human plasma versus human blood DBS.
AB  - BACKGROUND: Dried blood spots (DBS) sampling is a well-known technology for
      qualitative determination such as DNA analysis and screening of newborn metabolic
      disorders. The scientific community has recently expressed interest in applying
      the DBS technique for quantitative determination of drugs in biological fluid.
      RESULTS: Two new bioanalytical assays were developed and validated for the
      determination of naproxen in human plasma and in DBS samples using liquid
      chromatography coupled with tandem MS. Furthermore, plasma and DBS clinical
      samples were collected from four subjects enrolled as part of a bioequivalence
      study. Concentration data for plasma and DBS samples were determined and
      pharmacokinetic (PK) profiles in plasma and in DBS samples were compared.
      CONCLUSIONS: A strong correlation between PK data obtained by the DBS and
      conventional plasma method was observed, which makes DBS a valuable technique for
      further naproxen bioavailability and PK investigations and studies.

PMID- 21083353
TI  - Radiation Exposures in Medicine: Biological and Public Health Significance.
      American Statistical Association Conference on Radiation and Health. Annapolis,
      Maryland, June 13-16, 2010.

PMID- 21083351
TI  - Use of DBS sample collection to determine circulating drug concentrations in
      clinical trials: practicalities and considerations.
AB  - BACKGROUND: A clinical investigation was performed into the practicalities of the
      collection of blood samples for the determination of drug exposures on filter
      paper, known as dried blood spot (DBS) sampling using a two-period, single-dose,
      open-label trial conducted in 11 healthy volunteers who received a single oral
      dose of paracetamol. Questionnaires relating to the blood sampling and spotting
      process and tolerability were completed by staff and volunteers. Paracetamol
      concentrations in DBS samples obtained by venous cannula (DBS-Can) were compared
      against those from fingerprick (DBS-FP) and fresh whole blood obtained from a
      cannula (WB-Can). RESULTS: The questionnaires demonstrated that FP and blood
      spotting was easy to perform and well tolerated and compared favorably with
      cannula sampling. Paracetamol concentrations in DBS-Can were greater than those
      in WB-Can (positive bias) except below 8000 ng/ml when both were interchangeable.
      When comparing DBS-FP to DBS-Can, both the bias and variability differed
      significantly across the five sampling time points. CONCLUSION: The study has
      shown that the DBS technique is practical in the context of a clinical trial.
      Interchangeability of drug concentrations between blood sampling site and mode of
      blood collection has to be checked and taken into account when designing
      pharmacokinetic studies for other compounds.

PMID- 21083354
TI  - Gastric adenocarcinoma in a 13-year-old boy: a diagnosis not often seen in this
      age group.
AB  - Gastric adenocarcinoma is not uncommon in the adult population, but in the
      pediatric population it is an extremely rare entity. A 13-year-old boy was
      referred to a pediatric oncology unit for evaluation of a tumor in the upper
      abdomen. Further investigation revealed an advanced stage gastric carcinoma with
      metastases suggestive for a hereditary cause. Awareness for uncommon diagnoses is
      a key issue in regard of accurate treatment and overall prognosis.

PMID- 21083355
TI  - The effects of deferasirox on renal, cardiac and hepatic iron load in patients
      with beta-thalassemia major: preliminary results.
AB  - The iron loading related to erythrocyte transfusions is the major cause of
      morbidities and mortalities in patients with beta-thalassemia major (beta-TM).
      Deferasirox, an orally active iron chelator, has been reported to cause serum
      creatinine increases in addition to acute renal failures in elderly patients with
      comorbidities. The nefrotoxicities in patients using deferasirox, despite the
      facts that the drug is minimally excreted from kidneys and its effective
      chelation of iron from liver and heart, may rise the question of
      decomparmentalization of iron from these organs to kidneys. Thirteen patients
      with beta-TM were included in the study (mean age 18.5 +/- 7.5 years [9-33
      years]). The patients received deferasirox in a dose of 34.3 +/- 6.5 mg/kg [17-37
      mg/kg]. Four patients (31%) exhibited consecutive increases in serum creatinine
      greater than 33% above baseline twice during the follow-up period. The results
      indicated that the earliest iron chelation starts in liver in patients receiving
      deferasirox. Additionally, by the 6th month of deferasirox, the status of cardiac
      and renal iron in chronically transfused patients with beta-TM were preserved.
      This may indicate that the serum creatinine increases may not be attributed to
      iron decompartmantalization from other organs to kidneys.

PMID- 21083356
TI  - Experience of pandemic influenza with H1N1 in children with leukemia.
AB  - It is not exactly known the risks from infection with pandemic influenza (H1N1)
      2009 in children with leukemia. Here the authors present their experience in 5
      children with leukemia. Pandemic influenza (H1N1) 2009 was detected in 5 patients
      (F/M: 3/2) at their institution. The ages of these patients were between 2 and 16
      years. Four had acute lymphoblastic leukemia (ALL) and 1 acute myeloblastic
      leukemia (AML). Three of the ALL patients had the diagnosis of pandemic influenza
      (H1N1) 2009 at the same time as they were diagnosed with ALL. The remaining 2
      patients were receiving intensive chemotherapy. All patients had fever,
      rhinorrhea, and cough. Although bronchopneumonia was seen in 3 patients, only 1
      revealed respiratory distress. Stomach ache and diarrhea was seen in the patient
      who had no pneumonia. All treated as inpatients, but none of them required
      hospitalization in intensive care unit. One to 3 days after the symptoms of
      influenza appeared, oseltamivir (Tamiflu) was given to all patients in
      combination with broad-spectrum antibiotics. Fever declined to normal ranges in 1
      to 3 days after treatment was started. The patients received oseltamivir for 5 to
      7 days. Cell culture tests were found to be positive for influenza A and
      polymerase chain reaction (PCR) revealed H1N1 for all 5 patients. Although this
      is a very small case series, pandemic influenza (H1N1) 2009 did not seem to be
      very dangerous for children with leukemia if the oseltamivir treatment was given
      early when symptoms of influenza appeared.

PMID- 21083357
TI  - Effect of hydroxyurea on physical fitness indices in children with sickle cell
      anemia.
AB  - The current studies aimed at determining physical fitness indices and
      anthropometrics profiles of children with sickle cell anemia (SCA) after the use
      of hydroxyurea (HU). Ninety-three male schoolchildren--who participated
      previously in a similar study before the introduction of HU--comprising 2 groups
      participated in the studies. Group 1 was 41 children who were suffering from
      sickle cell disease (SCD) and were on HU for a minimum of 2 years, whereas group
      2 was 50 normal healthy controls. Anthropometrics measurement and parameters of
      physical fitness were assessed in all subjects. All children were also subjected
      to a minimum of 6-minute running exercise test on a flat motorized treadmill at
      speed corresponding to 5 km/h. Throughout the test heart rate was monitored and
      recorded during exercise and for 10 minutes during recovery. Blood hemoglobin
      (Hb) and HbF% were measured after the use of HU. The mean values of weight,
      height, and lean body mass were still lower in the SCD children (P < .05)
      compared with the healthy subjects. However, they had significant decrease in the
      mean heart rate values and they spent longer time on the treadmill before they
      got tired compared to their previous performance and were just below the normal
      controls. Hydroxyurea treatment improved the aerobic exercise tolerance and most
      of the physical fitness parameters in children with SCD.

PMID- 21083358
TI  - Prenatal control of hemoglobin H disease: is it possible?

PMID- 21083359
TI  - Molecular detection of tyrosine hydroxylase in the peripheral blood of patients
      with neuroblastoma: useful at diagnosis but not predictive of subsequent relapse
      during off-therapy follow-up.
AB  - In the present study, the authors analyzed the tyrosine hydroxylase (TH)
      expression in peripheral blood (PB) of neuroblastoma (NB) patients and
      investigated the clinical implications. From April 2005 to October 2008, a total
      of 683 PB specimens (64 at diagnosis, 244 during chemotherapy, 355 during off
      therapy follow-up, and 20 at relapse) acquired from 141 patients were
      investigated. TH expression was measured by quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR). TH-positive rate at diagnosis (21.4%) was
      higher than those during chemotherapy (0.8%) or off-therapy follow-up (1.7%). TH
      expression at diagnosis was associated with high-risk features (ie, advanced
      stage, older age, unfavorable pathology, and amplified N-myc) and the probability
      of 3-year relapse-free survival in the TH-positive patients was lower than in the
      TH-negative patients (45.8% +/- 27.8% versus 95.8% +/- 5.7%, P < .001). TH
      expression was positive in only 6 specimens during off-therapy follow-up.
      However, tumor relapse occurred in only 2 out of 6 TH-positive patients. In
      addition, TH expression was negative during previous off-therapy follow-up, prior
      to relapse, in 8 out of 10 relapsed patients. Whereas TH expression in PB at
      diagnosis was associated with high-risk features and a poorer outcome, TH
      expression during off-therapy follow-up had very limited value for the prediction
      of a subsequent relapse.

PMID- 21083360
TI  - Rituximab for child with chronic relapsing autoimmune hemolytic anemia.

PMID- 21083361
TI  - Life-threatening intracranial bleeding in a newborn with congenital
      cytomegalovirus infection: late-onset neonatal hemorrhagic disease.
AB  - The authors present a case of a 36-day-old infant with intracranial and
      intramuscular hemorrhage due to vitamin K deficiency bleeding, who received
      intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests
      showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent
      with vitamin K deficiency abnormality. Serological analyses showed that
      cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The
      infant was treated successfully with intravenous ganciclovir and blood products.
      This case suggests that it is imperative to meticulously investigate the etiology
      in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver
      disease caused by congenital cytomegalovirus infection should be in mind in term
      infants who presented with late-onset hemorrhagic disease.

PMID- 21083362
TI  - Acute respiratory distress syndrome as an initial presentation of hemophagocytic
      lymphohistiocytosis after induction therapy for acute myeloid leukemia.
AB  - A 7-month-old girl with acute myeloid leukemia (AML) developed acute respiratory
      distress syndrome (ARDS) during the pancytopenic period after induction
      chemotherapy. Respiratory failure did not improve despite intensive treatments.
      Eventually, hemophagocytic lymphohistiocytosis (HLH) was diagnosed based on
      hemophagocytosis in bone marrow, and high soluble interleukin-2 receptor (sIL-2R)
      and ferritin levels. Even after cyclosporin A was started against HLH, she did
      not recover. Autopsy showed macrophage proliferation in bone marrow and lymph
      nodes. HLH should be considered, even in the pancytopenic period after
      chemotherapy, when patients develop ARDS that does not respond to supportive
      therapies.

PMID- 21083363
TI  - Pattern of pediatric chronic myeloid leukemia in Sudan and hematological response
      to imatinib.
AB  - Chronic myeloid leukemia (CML) is infrequent in children. The best-known
      treatment is stem cell transplant. In a country with limited resources like
      Sudan, such expensive therapy is not available. Alternative approaches are needed
      to help these children. The tyrosine kinase inhibitor-imatinib-might be an answer
      to this problem. The objective of this study is to determine the pattern of
      children with CML, their hematological response to imatinib, and tolerance and
      side effects to this drug. All patients with confirmed BCR-ABL by polymerase
      chain reaction (PCR) were included in this study. The relevant data were
      collected and the patients were started on imatinib. Response to treatment was
      assessed clinically and hematologically only. Cytogenetics and molecular studies
      are not available. The average age of the 31 patient evaluated was 8.7 years, 2
      patients were less than 1 year, and 5 patients, ie, 16%, were 2 years old or
      less. Chloroma was observed in 6 (19%) patients. The average of the white blood
      cell (WBC) count was 206.6 x 10(9)/L and the platelet count average was 523 x
      10(9)/L. Two (6.5%) of the 31 patients presented as acute myeloid leukemia (AML).
      All patients had hematological remission within 2 months. Twenty-three (74%) had
      a sustained remission over an average follow-up period of 26 months (2-67
      months). Six (19%) patients died with AML or sepsis. Side effects to imatinib
      were infrequent, observed in 4 out of 29 (13.7%) patients, and mild. One patient
      only needed dose modification. No resistance was observed during this period. CML
      patients present at an earlier age than in other parts of the world. Imatinib is
      safe and effective in treating pediatric CML where stem cell transplant in not
      available. Further cytogenetics are important to monitor response and proper
      management.

PMID- 21083364
TI  - Detection of Epstein-Barr virus DNA in plasma and lymph node biopsy samples of
      pediatric and adult patients with Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is commonly associated with latent Epstein-Barr virus (EBV)
      infection. The aim of this study is a molecular analysis of the EBV status in
      both involved lymph node biopsies and plasma samples of patients with HL. Plasma
      and lymph node biopsy samples obtained from 15 pediatric and 10 adult HL patients
      were examined for EBV DNA using conventional polymerase chain reaction (PCR). The
      control group consisted of 30 healthy pediatrics and adults. In addition,
      immunoglobulin G (IgG) anti-EBV nuclear antigen (EBNA)-1 antibody was determined
      in sera of patients and controls using enzyme-linked immunosorbent assay (ELISA).
      IgG Anti EBNA-1 antibody was detected in 21 (84%) and 8 (26%) of patients and
      controls, respectively (P < .05). EBV DNA was detected in 12 (48%) and 1 (3%)
      plasma samples of patient and control cases, respectively. Significant difference
      was observed in plasma DNA detection between patients and controls (P < .05).
      Comparison of EBV DNA detection in plasma and biopsy samples between children and
      adult patients was only significant for plasma samples (P = .025). Significant
      correlation was observed in positive detection of EBV DNA between plasma and
      biopsy samples of the same individual (P < .001, r = .923). Frequency of EBV DNA
      in plasma and biopsy samples obtained from mixed-cellularity subgroup was higher
      than the nodular sclerosis; however, no significant difference was observed
      between these 2 subgroups. EBV detection in plasma of childhood Hodgkin lymphoma
      in a population with EBV seroconversion might be of value as a biomarker for EBV
      associated Hodgkin lymphoma.

PMID- 21083365
TI  - Severe head injury in children: intensive care unit activity and mortality in
      England and Wales.
AB  - OBJECTIVE: To explore the relationship between volume of paediatric intensive
      care unit (PICU) head injury (HI) admissions, specialist paediatric neurosurgical
      PICU practice, and mortality in England and Wales. METHODS: Analysis of HI cases
      (age  <16 years) from the Paediatric Intensive Care Audit Network national cohort
      of sequential PICU admissions in 27 units in England and Wales, in the 5 years
      2004-2008. Risk-adjusted mortality using the Paediatric Index of Mortality (PIM)
      model was compared between PICUs aggregated into quartile groups, first to fourth
      based on descending number of HI admissions/year: highest volume, medium-higher
      volume, medium-lower volume, and lowest volume. The effect of category of PICU
      interventions - observation only, mechanical ventilation (MV) only, and
      intracranial pressure (ICP) monitoring - on outcome was also examined.
      Observations were reported in relation to specialist paediatric neurosurgical
      PICU practice. RESULTS: There were 2575 admissions following acute HI (4.4% of
      non-cardiac surgery PICU admissions in England and Wales). PICU mortality was
      9.3%. Units in the fourth-quartile (lowest volume) group did not have significant
      specialist paediatric neurosurgical activity on the PICU; the other groups did.
      Overall, there was no effect of HI admissions by individual PICU on risk-adjusted
      mortality. However, there were significant effects for both intensive care
      intervention category (p<0.001) and HI admissions by grouping (p<0.005). Funnel
      plots and control charts using the PIM model showed a hierarchy in increasing
      performance from lowest volume (group IV), to medium-higher volume (group II), to
      highest volume (group I), to medium-lower volume (group III) sectors of the
      health care system. CONCLUSIONS: The health care system in England and Wales for
      critically ill HI children requiring PICU admission performs as expected in
      relation to the PIM model. However, the lowest-volume sector, comprising 14 PICUs
      with little or no paediatric neurosurgical activity on the unit, exhibits worse
      than expected outcome, particularly in those undergoing ICP monitoring. The best
      outcomes are seen in units in the mid-volume sector. These data do not support
      the hypothesis that there is a simple relationship between PICU volume and
      performance.

PMID- 21083366
TI  - Management of the ventriculo-peritoneal shunt in pediatric patients during robot
      assisted laparoscopic urologic procedures.
AB  - INTRODUCTION: Infection or malfunction of ventriculo-peritoneal (VP) shunts is a
      severe complication during laparoscopic surgery involving the gastrointestinal or
      urinary tract. It has been recently suggested to externalize the shunt or convert
      into a ventriculo-atrial shunt to prevent this complication with laparoscopic
      approach. Herein, we present a novel technique for management of the VP shunt
      during robot-assisted laparoscopic (RAL) urologic procedures. MATERIALS AND
      METHODS: After port placement and diagnostic peritoneoscopy, an Endopouch bag
      (Ethicon Endo-Surgery) was inserted into the peritoneal cavity and the distal end
      of the shunt was placed into the pouch. The Endopouch suture was synched around
      the shunt and the pouch was placed in the subhepatic space during the surgery.
      The intraperitoneal pressure was maintained at 12 mm Hg during the entire
      procedure. Metronidazole, gentamicin, and vancomycin were administered as
      prophylaxis. Following the completion of the surgery and profuse irrigation of
      the peritoneal cavity, the shunt was repositioned within the peritoneum. We
      evaluated perioperative shunt-related complications. RESULTS: We used this
      technique in four patients with VP shunt undergoing RAL cystoplasty and
      appendicovesicostomy and/or colonic enema channel formation. The average age of
      the patient at surgery was 10.8 (7-14) years. One patient was converted to open
      because of failure to progress due to multiple adhesions and the shunt was
      externalized temporarily. At a mean follow-up of 13 (3-20) months, no shunt
      related complications were seen. CONCLUSIONS: In our preliminary experience, the
      use of an intracorporeal Endopouch bag with controlled pneumoperitoneal pressure
      to protect the VP shunt may be an effective alternative to prevent complications
      related to it during RAL urologic surgery involving the gastrointestinal or
      urinary tract. Further studies will be needed to confirm our results.

PMID- 21083367
TI  - Isoflavones: effects on bone health.
AB  - BACKGROUND: There are many effects described, both experimental and clinical,
      that assess the relationship between isoflavones and bone. It has been
      hypothesized that isoflavones may have a positive effect on bone health.
      OBJECTIVE: To review the effects of isoflavones on biochemical markers of bone
      remodeling, bone density and bone quality, and finally on fracture incidence.
      METHODS: A systematic review was carried out of in vitro, animal, and human
      studies involving isoflavones and bone health. An electronic search was made,
      based on Internet search engines, MEDLINE (1966-June 2010) and the Cochrane
      Controlled Clinical Trials Register. This search was further supplemented by a
      hand-search of reference lists of selected review papers. RESULTS: After crossing
      cleaning the reference lists, 737 studies dealing with isoflavones and bone were
      identified. Of these, 36 were considered selectable. From in vitro and animal
      studies, isoflavones appear to stimulate osteoblastic bone formation and inhibit
      osteoclastic bone resorption. Reviewed data show evidence of a beneficial effect
      of isoflavones on bone health in peri- and postmenopausal women when high
      isoflavone soy protein is incorporated in the diet. Inconsistencies observed
      among data from different studies are related to differences in study design, the
      variety of soy sources of isoflavones, time of analysis, and the variability in
      the bioavailability and metabolism of isoflavones. CONCLUSIONS: Most of the
      studies suggested a positive relationship between isoflavones and bone health.
      Further well-controlled, randomized, double-blind, clinical trials with a larger
      sample population, longer duration, and examination of various dosages are needed
      to better elucidate the inter-relationship between isoflavones and bone loss and
      to clarify whether isoflavones could prevent bone fractures.

PMID- 21083368
TI  - What is the best equation to estimate the basal energy expenditure of climacteric
      women?
AB  - OBJECTIVES: The methods currently available for the measurement of energy
      expenditure in patients, such as indirect calorimetry and double-labelled water,
      are expensive and are limited in Brazil to research projects. Thus, equations for
      the prediction of resting metabolic rate appear to be a viable alternative for
      clinical practice. However, there are no specific equations for the Brazilian
      population and few studies have been conducted on Brazilian women in the
      climacteric period using existing and commonly applied equations. On this basis,
      the objective of the present study was to investigate the concordance between the
      predictive equations most frequently used and indirect calorimetry for the
      measurement of resting metabolic rate. METHODS: We calculated the St. Laurent
      concordance correlation coefficient between the equations and resting metabolic
      rate calculated by indirect calorimetry in 46 climacteric women. RESULTS: The
      equation showing the best concordance was that of the FAO/WHO/UNU formula (0.63),
      which proved to be better than the Harris & Benedict equation (0.55) for the
      sample studied. CONCLUSIONS: On the basis of the results of the present study, we
      conclude that the FAO/WHO/UNU formula can be used to predict better the resting
      metabolic rate of climacteric women. Further studies using more homogeneous and
      larger samples are needed to permit the use of the FAO/WHO/UNU formula for this
      population group with greater accuracy.

PMID- 21083369
TI  - Geographic and temporal variations in population dynamics of Ixodes ricinus and
      associated Borrelia infections in The Netherlands.
AB  - In a countrywide investigation of the ecological factors that contribute to Lyme
      borreliosis risk, a longitudinal study on population dynamics of the sheep tick
      Ixodes ricinus and their infections with Borrelia burgdorferi sensu lato (s.l.)
      was undertaken at 24 sites in The Netherlands from July 2006 to December 2007.
      Study sites were mature forests, dune vegetations, or new forests on land
      reclaimed from the sea. Ticks were sampled monthly and nymphal ticks were
      investigated for the presence of Borrelia spp. I. ricinus was the only tick
      species found. Ticks were found in all sites, but with significant spatial and
      temporal variations in density between sites. Peak densities were found in July
      and August, with lowest tick numbers collected in December and January. In some
      sites, questing activities of I. ricinus nymphs and adults were observed in the
      winter months. Mean monthly Borrelia infections in nymphs varied from 0% to 29.0%
      (range: 0%-60%), and several sites had significantly higher mean nymphal Borrelia
      infections than others. Four genospecies of Borrelia burgdorferi s.l. were found,
      with B. afzelii being dominant at most sites. Borrelia infection rates in nymphal
      ticks collected in July, September, and November 2006 were significantly higher
      (23.7%, p<0.01) than those in the corresponding months of 2007 (9.9%). The
      diversity in Borrelia genospecies between sites was significantly different
      (p<0.001). Habitat structure (tree cover) was an effective discriminant parameter
      in the determination of Borrelia infection risk, as measured by the proportion of
      nymphal ticks infected with B. burgdorferi s.l. Thickness of the litter layer and
      moss cover were positively related to nymphal and adult tick densities. The study
      shows that Borrelia-infected ticks are present in many forest and dune areas in
      The Netherlands and suggests that in such biotopes, which are used for a wide
      variety of recreational activities, the infection risk is high.

PMID- 21083370
TI  - The occurrence of spotted fever rickettsioses and other tick-borne infections in
      forest workers in Poland.
AB  - The presence of antibodies to Rickettsia conorii, R. helvetica, R. felis, R.
      slovaca, R. sibirica, and R. massiliae in sera of 129 forest workers from
      northeastern and southern Poland was assayed by indirect immunofluorescence.
      Previous environmental studies revealed presence of spotted fever group (SFG)
      rickettsiae in ticks collected from these areas. Additionally, the workers were
      examinated for the presence of antibodies specific to other tick-borne bacteria:
      Anaplasma phagocytophilum, Bartonella spp., and B. burgdorferi. The results of
      the studies have shown the presence of specific SFG rickettsiae antibodies in
      14.7% of tested forest workers, among them 78.9% had species-specific antibodies
      to R. massiliae. Contrary to previous detection R. helvetica and R. slovaca in
      ticks collected in the environment of the examined area, no species-specific
      antibodies to these species were detected in studied workers. Antibodies to B.
      burgdorferi (44%) were found in forest workers more often than antibodies to
      other tested pathogens. B. burgdorferi was also the main component of
      coinfections. The most frequent confirmed serologically coinfections were
      simultaneous infections with B. burgdorferi and Bartonella spp. found in 10% of
      tested individuals. So far, SFG rickettsiae infections have not been diagnosed in
      Poland; however, the presence of the bacteria in ticks and presence of specific
      antibodies in humans exposed to arthropods show the need for monitoring the
      situation. The list of tick-borne pathogens is increasing, but knowledge about
      the possibility of humans acquiring multipathogens infections after tick bite
      still needs evaluation.

PMID- 21083372
TI  - Hyr1 protein and beta-glucan conjugates as anti-Candida vaccines.

PMID- 21083375
TI  - Concurrent Crimean-Congo hemorrhagic fever and visceral leishmaniasis in a
      Turkish girl.
AB  - In this article, a case of Crimean-Congo hemorrhagic fever (CCHF) and visceral
      leishmaniasis coinfection in a 14-month-old girl is reported. The case has been
      evaluated according to two different points of view based on the coexistence of
      CCHF and visceral leishmaniasis and a strongly suggested horizontal transmission
      of CCHF from her father. To the best of our knowledge, this coinfection has not
      been previously reported in literature.

PMID- 21083371
TI  - Genetic associations of variants in genes encoding HIV-dependency factors
      required for HIV-1 infection.
AB  - BACKGROUND: High-throughput genome-wide techniques have facilitated the
      identification of previously unknown host proteins involved in cellular human
      immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used
      small interfering RNA technology to silence each gene in the human genome to
      determine the importance of each in HIV infection. Genes conferring a significant
      effect were termed HIV-dependency factors (HDFs). METHODS: We assembled high
      density panels of 6380 single-nucleotide polymorphisms (SNPs) in 278 HDF genes
      and tested for genotype associations with HIV infection and AIDS progression in
      1633 individuals from clinical AIDS cohorts. RESULTS: After statistical
      correction for multiple tests, significant associations with HIV acquisition were
      found for SNPs in 2 genes, NCOR2 and IDH1. Weaker associations with AIDS
      progression were revealed for SNPs within the TM9SF2 and EGFR genes. CONCLUSIONS:
      This study independently verifies the influence of NCOR2 and IDH1 on HIV
      transmission, and its findings suggest that variation in these genes affects
      susceptibility to HIV infection in exposed individuals.

PMID- 21083376
TI  - Comparison of post-Lyme Borreliosis symptoms in erythema migrans patients with
      positive and negative Borrelia burgdorferi sensu lato skin culture.
AB  - PURPOSE: Limited data exist on differences of erythema migrans patients with
      either positive or negative Borrelia burgdorferi sensu lato skin culture.
      METHODS: We analyzed 252 adult patients with erythema migrans in whom skin biopsy
      specimen was cultured for the presence of B. burgdorferi sensu lato. Evaluations
      of epidemiological, clinical, and microbiological findings were conducted at
      baseline, 14 days, 2, 6, and 12 months after treatment with either doxycycline or
      cefuroxime axetil. RESULTS: One hundred fifty-one (59.9%) patients had positive
      skin culture (86.9% B. afzelii, 8.0% B. garinii, 5.1% B. burgdorferi sensu
      stricto) and 101 (40.1%) had negative skin culture. Patients in the culture
      positive and culture-negative groups were comparable for the basic demographic,
      epidemiological, clinical, and laboratory characteristics at presentation.
      Statistically significantly worse selected treatment outcome parameters in the
      culture-positive group compared with the culture-negative group were established
      during follow-up. Treatment failure was documented in two patients who were
      culture positive and in none in the culture-negative group. CONCLUSIONS: Although
      findings for the pretreatment characteristics were comparable between the
      erythema migrans skin culture-positive and culture-negative patients, some
      parameters indicate that borrelia skin culture positivity may predict a less
      favorable treatment outcome.

PMID- 21083377
TI  - Taking the guesswork out of uveal melanoma.

PMID- 21083378
TI  - Beyond repeal--the future of health care reform.

PMID- 21083379
TI  - Responding to an FDA warning--geographic variation in the use of rosiglitazone.

PMID- 21083380
TI  - Mutations in GNA11 in uveal melanoma.
AB  - BACKGROUND: Uveal melanoma is the most common intraocular cancer. There are no
      effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding
      an alpha subunit of heterotrimeric G proteins, are found in 40% of uveal
      melanomas. METHODS: We sequenced exon 5 of GNAQ and GNA11, a paralogue of GNAQ,
      in 713 melanocytic neoplasms of different types (186 uveal melanomas, 139 blue
      nevi, 106 other nevi, and 282 other melanomas). We sequenced exon 4 of GNAQ and
      GNA11 in 453 of these samples and in all coding exons of GNAQ and GNA11 in 97
      uveal melanomas and 45 blue nevi. RESULTS: We found somatic mutations in exon 5
      (affecting Q209) and in exon 4 (affecting R183) in both GNA11 and GNAQ, in a
      mutually exclusive pattern. Mutations affecting Q209 in GNA11 were present in 7%
      of blue nevi, 32% of primary uveal melanomas, and 57% of uveal melanoma
      metastases. In contrast, we observed Q209 mutations in GNAQ in 55% of blue nevi,
      45% of uveal melanomas, and 22% of uveal melanoma metastases. Mutations affecting
      R183 in either GNAQ or GNA11 were less prevalent (2% of blue nevi and 6% of uveal
      melanomas) than the Q209 mutations. Mutations in GNA11 induced spontaneously
      metastasizing tumors in a mouse model and activated the mitogen-activated protein
      kinase pathway. CONCLUSIONS: Of the uveal melanomas we analyzed, 83% had somatic
      mutations in GNAQ or GNA11. Constitutive activation of the pathway involving
      these two genes appears to be a major contributor to the development of uveal
      melanoma. (Funded by the National Institutes of Health and others.).

PMID- 21083381
TI  - Images in clinical medicine. The jaw-thrust maneuver.

PMID- 21083382
TI  - A flood of opioids, a rising tide of deaths.

PMID- 21083383
TI  - Up in the air--suspending ethical medical practice.

PMID- 21083385
TI  - Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation.
AB  - BACKGROUND: A new approach in the treatment of cystic fibrosis involves improving
      the function of mutant cystic fibrosis transmembrane conductance regulator
      (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of
      wild-type and defective cell-surface CFTR in vitro. METHODS: We randomly assigned
      39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral
      VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in
      part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or
      placebo for 28 days (in part 2 of the study). RESULTS: At day 28, in the group of
      subjects who received 150 mg of VX-770, the median change in the nasal potential
      difference (in response to the administration of a chloride-free isoproterenol
      solution) from baseline was -3.5 mV (range, -8.3 to 0.5; P=0.02 for the within
      subject comparison, P=0.13 vs. placebo), and the median change in the level of
      sweat chloride was -59.5 mmol per liter (range, -66.0 to -19.0; P=0.008 within
      subject, P=0.02 vs. placebo). The median change from baseline in the percent of
      predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3;
      P=0.008 for the within-subject comparison, P=0.56 vs. placebo). None of the
      subjects withdrew from the study. Six severe adverse events occurred in two
      subjects (diffuse macular rash in one subject and five incidents of elevated
      blood and urine glucose levels in one subject with diabetes). All severe adverse
      events resolved without the discontinuation of VX-770. CONCLUSIONS: This study to
      evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was
      associated with within-subject improvements in CFTR and lung function. These
      findings provide support for further studies of pharmacologic potentiation of
      CFTR as a means to treat cystic fibrosis. (Funded by Vertex Pharmaceuticals and
      others; ClinicalTrials.gov number, NCT00457821.).

PMID- 21083387
TI  - Bisphosphonates for osteoporosis.

PMID- 21083386
TI  - Outcomes of kidney transplantation in HIV-infected recipients.
AB  - BACKGROUND: The outcomes of kidney transplantation and immunosuppression in
      people infected with human immunodeficiency virus (HIV) are incompletely
      understood. METHODS: We undertook a prospective, nonrandomized trial of kidney
      transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least
      200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels
      while being treated with a stable antiretroviral regimen. Post-transplantation
      management was provided in accordance with study protocols that defined
      prophylaxis against opportunistic infection, indications for biopsy, and
      acceptable approaches to immunosuppression, management of rejection, and
      antiretroviral therapy. RESULTS: Between November 2003 and June 2009, a total of
      150 patients underwent kidney transplantation; survivors were followed for a
      median period of 1.7 years. Patient survival rates (+/-SD) at 1 year and 3 years
      were 94.6+/-2.0% and 88.2+/-3.8%, respectively, and the corresponding mean graft
      survival rates were 90.4% and 73.7%. In general, these rates fall somewhere
      between those reported in the national database for older kidney-transplant
      recipients (>=65 years) and those reported for all kidney-transplant recipients.
      A multivariate proportional-hazards analysis showed that the risk of graft loss
      was increased among patients treated for rejection (hazard ratio, 2.8; 95%
      confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte
      globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03);
      living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8;
      P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3
      year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52),
      respectively. HIV infection remained well controlled, with stable CD4+ T-cell
      counts and few HIV-associated complications. CONCLUSIONS: In this cohort of
      carefully selected HIV-infected patients, both patient- and graft-survival rates
      were high at 1 and 3 years, with no increases in complications associated with
      HIV infection. The unexpectedly high rejection rates are of serious concern and
      indicate the need for better immunotherapy. (Funded by the National Institute of
      Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

PMID- 21083388
TI  - Influenza vaccines for the future.

PMID- 21083389
TI  - Images in clinical medicine. Meckel's diverticulum.

PMID- 21083390
TI  - Case records of the Massachusetts General Hospital. Case 35-2010. A 56-year-old
      man with cough, hypoxemia, and rash.

PMID- 21083391
TI  - Targeting the basic defect in cystic fibrosis.

PMID- 21083392
TI  - Tackling the unknowns in HIV-related kidney diseases.

PMID- 21083393
TI  - Medical malpractice liability in the age of electronic health records.

PMID- 21083394
TI  - Proteinuria, the podocyte, and insulin resistance.

PMID- 21083395
TI  - Sensor-augmented insulin-pump therapy in type 1 diabetes.

PMID- 21083396
TI  - Sensor-augmented insulin-pump therapy in type 1 diabetes.

PMID- 21083398
TI  - Rituximab or cyclophosphamide in ANCA-associated renal vasculitis.

PMID- 21083399
TI  - Rituximab or cyclophosphamide in ANCA-associated renal vasculitis.

PMID- 21083400
TI  - Rituximab or cyclophosphamide in ANCA-associated renal vasculitis.

PMID- 21083401
TI  - Rituximab or cyclophosphamide in ANCA-associated renal vasculitis.

PMID- 21083403
TI  - More on physician cost profiling.

PMID- 21083405
TI  - Genomewide association studies and assessment of risk of disease.

PMID- 21083406
TI  - Genomewide association studies and assessment of risk of disease.

PMID- 21083411
TI  - Is basic personality related to violent and non-violent video game play and
      preferences?
AB  - Based on the uses and gratifications perspective, personality was expected to
      relate to violent video game play frequency and game preferences. Participants
      completed measures of personality and frequency of violent video game play, and
      identified their most frequently played video games. Results indicate that
      individuals higher in openness but lower in agreeableness played violent video
      games more frequently. In addition, more open and extroverted but less agreeable
      and neurotic individuals generally preferred to play video games that are more
      violent. Results suggest personality may be more predictive of violent video game
      use than traditional media use, though the predictive personality dimensions may
      be consistent across media types.

PMID- 21083412
TI  - A 48-week pilot study switching suppressed patients to darunavir/ritonavir and
      etravirine from enfuvirtide, protease inhibitor(s), and non-nucleoside reverse
      transcriptase inhibitor(s).
AB  - Treatment options for HIV-infected patients can be limited due to viral drug
      resistance to antiretroviral agents. Enfuvirtide (ENF) is an injectable
      entry/fusion inhibitor that is effective in achieving viral suppression when used
      in combination with protease inhibitors (PIs) in patients with pre-existing
      resistance. However, ENF treatment is associated with injection site reactions
      and dosing fatigue. This multicenter, open-label, Phase IIIb, 48-week pilot study
      assessed safety, tolerability, and effectiveness of the PI darunavir (DRV),
      boosted with ritonavir (DRV/r), and the non-nucleoside reverse transcriptase
      inhibitor (NNRTI) etravirine (ETR), when substituted for ENF/PI (+/-NNRTI)-based
      therapy. Ten virologically suppressed (HIV RNA less than 50 copies/ml) men who
      were intolerant to ENF were enrolled. Median (range) CD4+ count was 301 (187-663)
      cells/mm(3). Two patients discontinued the study; all remaining patients
      maintained a viral load of less than 50 copies/ml at Week 48. Viral load
      increased to greater than 50 copies/ml in two patients, but was eventually re
      suppressed without the need for changes in treatment. Median (range) increase
      (last observation carried forward) in CD4+ count from baseline to Week 48 was 64
      (-53-100) cells/mm(3). Two grade 3 adverse events (AEs), nausea and weight loss,
      and one serious AE, acute cholecystitis, were reported; each AE resolved without
      treatment interruption. Most common AEs related to study drug were fatigue, rash,
      headache, and diarrhea. Decreases in triglycerides, low-density lipoprotein, and
      high-density lipoprotein, were observed. This study suggests that a DRV/r- and
      ETR-based regimen can be substituted for an ENF-based regimen while maintaining
      virologic suppression.

PMID- 21083413
TI  - Short communication: three years follow-up of first-line antiretroviral therapy
      in cambodia: negative impact of prior antiretroviral treatment.
AB  - There are few long-term data on ART-experienced patients in resource-limited
      settings. We performed a cross-sectional study of HIV-infected patients included
      in the ESTHER program in Calmette hospital, Phnom Penh, Cambodia, after 36 +/- 3
      months of cART. Therapeutic, clinical, and immunovirological outcomes were
      compared between patients who stated they were ART-naive (naive group), dual
      nucleoside reverse-transcriptase inhibitor (two-NRTI group), or fixed-dose
      combination of stavudine/lamivudine/nevirapine experienced (three-drug group) at
      entry to the program. A logistic regression model was used to evaluate the
      factors associated with virological failure (PCR HIV > 250 copies/ml). Among the
      256 patients included in the analysis, 148 (58%) were ART naive while 50 (20%)
      had previously received two NRTIs and 58 (22%) three drugs. At entry to the
      program, all the patients received two NRTIs and one nonnucleoside reverse
      transcriptase inhibitor (NNRTI). At evaluation, 46 patients (18%) were switched
      to a protease inhibitor-based regimen (9%, 32%, and 29% of the naive, two-NRTI,
      and three-drug groups; p < 0.0001). The median CD4 cell count increase was
      180/MUl overall (IQR: 96-276) and was higher in ART-naive than ART-experienced
      patients. In the intent-to-treat analysis, virological success was achieved in
      83.5%, 67%, and 69% of the naive, two-NRTI, and three-drug groups, respectively
      (p = 0.002). Factors associated with virological failure were suboptimal previous
      ART exposure and WHO immunological failure criteria. The long-term efficacy of
      first-line cART is maintained in Cambodia. In ART-experienced patients, viral
      load monitoring needs to be available to establish early virological failure and
      preserve the potency of second line regimens.

PMID- 21083414
TI  - A diffusion tensor imaging study on the white matter skeleton in individuals with
      sports-related concussion.
AB  - Recognizing and managing the effects of cerebral concussion is very challenging,
      given the discrete symptomatology. Most individuals with sports-related
      concussion will not score below 15 on the Glasgow Coma Scale, but will present
      with rapid onset of short-lived neurological impairment, demonstrating no
      structural changes on traditional magnetic resonance imaging (MRI) and computed
      tomography (CT) scans. The return-to-play decision is one of the most difficult
      responsibilities facing the physician, and so far this decision has been
      primarily based on neurological examination, symptom checklists, and
      neuropsychological (NP) testing. Diffusion tensor imaging (DTI) may be a more
      objective tool to assess the severity and recovery of function after concussion.
      We assessed white matter (WM) fiber tract integrity in varsity level college
      athletes with sports-related concussion without loss of consciousness, who
      experienced protracted symptoms for at least 1 month after injury. Evaluation of
      fractional anisotropy (FA) and mean diffusivity (MD) of the WM skeleton using
      tract-based spatial statistics (TBSS) revealed a large cluster of significantly
      increased MD for concussed subjects in several WM fiber tracts in the left
      hemisphere, including parts of the inferior/superior longitudinal and fronto
      occipital fasciculi, the retrolenticular part of the internal capsule, and
      posterior thalamic and acoustic radiations. Qualitative comparison of average FA
      and MD suggests that with increasing level of injury severity (ranging from
      sports-related concussion to severe traumatic brain injury), MD might be more
      sensitive at detecting mild injury, whereas FA captures more severe injuries. In
      conclusion, the TBSS analysis used to evaluate diffuse axonal injury of the WM
      skeleton seems sensitive enough to detect structural changes in sports-related
      concussion.

PMID- 21083415
TI  - Long-term benefit of human fetal neuronal progenitor cell transplantation in a
      clinically adapted model after traumatic brain injury.
AB  - Experimental human fetal neural progenitor cell (hfNPC) transplantation has
      proven to be a promising therapeutic approach after traumatic brain injury (TBI).
      However, the long-term efficacy and safety, which are both highly important for
      clinical translation of this approach, have thus far not been investigated. This
      study investigated the effect of local (L, 1 * 10(5) cells) and systemic (S, 5 *
      10(5) cells) administration of PKH-26-labeled pre-differentiated hfNPCs over a
      period of 12 weeks, beginning 24 h after severe controlled cortical impact TBI in
      Sprague-Dawley rats. Accelerating rotarod testing revealed a trend toward
      functional improvement beginning 1 week after transplantation, and persisting
      until the end of the experiment. The traumatic lesion volume as quantified by
      magnetic resonance imaging was smaller in both treatment groups compared to
      control (C) animals (C = 54.50 mm(3), L = 32 mm(3), S = 37.50 mm(3)).
      Correspondingly, neuronal (NeuN) staining showed increased neuronal survival at
      the border of the lesion in both transplanted groups (S = 92.4%; L = 87.2%;
      72.5%). Histological analysis of the brain compartments revealed transiently
      increased angiogenesis and reduced astroglial reaction during the first 4 weeks
      post-transplantation. PKH-26-positive cells were detected exclusively after local
      transplantation without any evidence of tumor formation. However, graft
      differentiation was seen only in very rare cases. In conclusion, transplantation
      of hfNPCs improved the long-term functional outcome after TBI, diminished trauma
      lesion size, and increased neuronal survival in the border zone of the lesion.
      This therapeutic effect was not likely due to cell replacement, but was
      associated with transiently increased angiogenesis and reduced astrogliosis.

PMID- 21083416
TI  - Preclinical efficacy testing in middle-aged rats: nicotinamide, a novel
      neuroprotectant, demonstrates diminished preclinical efficacy after controlled
      cortical impact.
AB  - Age is a consistent predictor of poor outcome following traumatic brain injury
      (TBI). Although the elderly population has one of the highest rates of TBI
      related hospitalization and death, few preclinical studies have attempted to
      model and treat TBI in the aged population. Recent studies have indicated that
      nicotinamide (NAM), a soluble B-group vitamin, improved functional recovery in
      experimental models of TBI in young animals. The purpose of the present study was
      to examine the preclinical efficacy of NAM in middle-aged rats. Groups of middle
      aged (14-month-old) rats were assigned to NAM (500 mg/kg or 50 mg/kg) or saline
      alone (1 mL/kg) treatment conditions, and received unilateral cortical contusion
      injuries (CCI) and injections at 1 h and 24 h following injury. The animals were
      tested on a variety of tasks to assess vestibulomotor (tapered beam) and
      cognitive performance (reference and working memory in the Morris water maze),
      and were evaluated for lesion size, blood-brain barrier compromise, astrocytic
      activation, and edema formation. In summary, the preclinical efficacy of NAM as a
      treatment following CCI in middle-aged rats differs from that previously
      documented in younger rats; while treatment with 50 mg/kg NAM appeared to have no
      effect, the 500-mg/kg dose worsened performance in middle-aged animals.
      Histological indicators demonstrated more nuanced group differences, indicating
      that NAM may positively impact some of the cellular cascades following injury,
      but were not substantial enough to improve functional recovery. These findings
      emphasize the need to examine potential treatments for TBI utilizing non-standard
      populations, and may explain why so many treatments have failed in clinical
      trials.

PMID- 21083417
TI  - Impact of cervical spine management brain injury on functional survival outcomes
      in comatose, blunt trauma patients with extremity movement and negative cervical
      spine CT: application of the Monte Carlo simulation.
AB  - Cervical spine (CS) magnetic resonance imaging (MRI) and collar use may prevent
      quadriplegia, yet create brain injury. We developed a computer model to assess
      the effect of CS management strategies on outcomes in comatose, blunt trauma
      patients with extremity movement and a negative CS CT scan. Strategies include
      early collar removal (ECR), ECR & MRI, late collar removal (LCR), and LCR & MRI.
      MRI risks include hypoxia, hypotension, increased intracranial pressure (?ICP),
      and ventilator-associated pneumonia (VAP). LCR risks include ?ICP, VAP, and
      delirium. Model elements include Quadriplegia and Primary, Secondary, LCR, and
      MRI Brain Injury. The Monte Carlo simulation determines health outcomes
      (Functional Survival versus Quadriplegia, Severe Brain Disability, or Dead).
      Utility values are Functional Survival 0.90, Quadriplegia 0.20, Severe Brain
      Disability 0.10, and Dead 0.00. Years of life expectancy are Functional Survival
      39.5, Quadriplegia 20.0, Severe Brain Disability 20.0, and Dead 0.0. Unstable CS
      rate 2.5%: Functional Survival/1,000: Unstable Patients: ECR 384, LCR 350, LCR &
      MRI 332, ECR & MRI 331; High-Risk Patients: ECR 161, LCR 151, LCR & MRI 140, ECR
      & MRI 153; Stable Patients: ECR 596, LCR 587, LCR & MRI 573, ECR & MRI 595.
      Quality-Adjusted Life Months for Unstable, High-Risk, and Stable Patients are
      greater with ECR; Stable Patient ECR and ECR & MRI are similar. Unstable CS rate
      0.5%: Functional Survival/1000: Unstable Patients: ECR 394, LCR 352, LCR & MRI
      332, ECR & MRI 332; High-Risk Patients: ECR 164, LCR 151, LCR & MRI 140, ECR &
      MRI 152; Stable Patients: ECR 611, LCR 592, LCR & MRI 576, ECR & MRI 598. Quality
      Adjusted Life Months for Unstable, High-Risk, and Stable Patients are greater
      with ECR. LCR and MRI brain injury results in losses of functional survivorship
      that exceed those from quadriplegia. Model results suggest that early collar
      removal without cervical spine MRI is a reasonable, and likely the preferable,
      cervical spine management strategy for comatose, blunt trauma patients with
      extremity movement and a negative cervical spine CT scan.

PMID- 21083418
TI  - Hair follicle-derived smooth muscle cells and small intestinal submucosa for
      engineering mechanically robust and vasoreactive vascular media.
AB  - Our laboratory recently reported a new source of smooth muscle cells (SMCs)
      derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high
      proliferation and clonogenic potential as well as contractile function. In this
      study, we aimed at engineering the vascular media using HF-SMCs and a natural
      biomaterial, namely small intestinal submucosa (SIS). Engineering functional
      vascular constructs required application of mechanical force, resulting in actin
      reorganization and cellular alignment. In turn, cell alignment was necessary for
      development of receptor- and nonreceptor-mediated contractility as soon as 24 h
      after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and
      secreted collagen and elastin, the two major extracellular matrix components of
      the vessel wall. At 2 weeks, vascular reactivity increased significantly up to
      three- to fivefold and mechanical properties were similar to those of native
      ovine arteries. Taken together, our data demonstrate that the combination of HF
      SMCs with SIS resulted in mechanically strong, biologically functional vascular
      media with potential for arterial implantation.

PMID- 21083419
TI  - A bilayer construct controls adipose-derived stem cell differentiation into
      endothelial cells and pericytes without growth factor stimulation.
AB  - This work describes the differentiation of adipose-derived mesenchymal stem cells
      (ASC) in a composite hydrogel for use as a vascularized dermal matrix. Our intent
      is that such a construct could be utilized following large-surface-area burn
      wounds that require extensive skin grafting and that are limited by the
      availability of uninjured sites. To develop engineered skin replacement
      constructs, we are pursuing the use of ASC. We have established that a PEGylated
      fibrin gel can provide a suitable environment for the proliferation of ASC over a
      7 day time course. Further, we have demonstrated that PEGylated fibrin can be
      used to control ASC differentiation toward vascular cell types, including cells
      characteristic of both endothelial cells and pericytes. Gene expression analysis
      revealed strong upregulation of endothelial markers, CD31, and von Willebrand
      factor, up to day 11 in culture with corresponding evidence of protein expression
      demonstrated by immunocytochemical staining. ASC were not only shown to express
      endothelial cell phenotype, but a subset of the ASC expressed pericyte markers.
      The NG2 gene was upregulated over 11 days with corresponding evidence for the
      cell surface marker. Platelet-derived growth factor receptor beta gene expression
      decreased as the multipotent ASC differentiated up to day 7. Increased receptor
      expression at day 11 was likely due to the enhanced pericyte gene expression
      profile, including increased NG2 expression. We have also demonstrated that when
      cells are loaded onto chitosan microspheres and sandwiched between the PEGylated
      fibrin gel and a type I collagen gel, the cells can migrate and proliferate
      within the two different gel types. The matrix composition dictates the lineage
      specification and is not driven by soluble factors. Utilizing an insoluble
      bilayer matrix to direct ASC differentiation will allow for the development of
      both vasculature as well as dermal connective tissue from a single population of
      ASC. This work underscores the importance of the extracellular matrix in
      controlling stem cell phenotype. It is our goal to develop layered composites as
      wound dressings or vascularized dermal equivalents that are not limited by
      nutrient diffusion.

PMID- 21083421
TI  - Forkhead Box O transcription factors: key players in redox signaling.
AB  - The Forkhead Box O (FOXO) transcription factors are famous for their role in
      longevity: both Caenorhabditis elegans and Drosophila melanogaster can extend
      their median and maximum lifespan in a FOXO-dependent manner, and certain single
      nucleotide polymorphisms in human FOXO genes are associated with reaching an age
      above 100 years. Ablation of FOXO1, 3a, and 4 in adult mice predisposes them to
      tumorigenesis and stem cell depletion, and the latter could at least partly be
      reversed by treatment with antioxidants. Indeed, FOXO has been known to regulate
      the defense against reactive oxygen species through transactivation of
      antioxidant genes like manganese superoxide dismutase and catalase. At the same
      time, reactive oxygen species regulate FOXO activity in many ways through an
      elaborate combination of activating as well as repressing post-translational
      modifications, including phosphorylation, acetylation, ubiquitinylation, and
      methylation. Hence, FOXO is at the centre of redox signaling, but it is unclear
      whether and how exactly redox signaling to and from FOXO contributes to its
      effects on longevity. In this forum issue we give an overview of the many facets
      of FOXO in worms, flies, mice, and humans.

PMID- 21083420
TI  - Role of the inducible nitric oxide synthase in the onset of fructose-induced
      steatosis in mice.
AB  - To test the hypothesis that the inducible nitric oxide synthase (iNOS) is
      involved in mediating the toll-like receptor 4-dependent effects on the liver in
      the onset of fructose-induced steatosis, wild-type and iNOS knockout (iNOS(-/-))
      mice were either fed tap water or 30% fructose solution for 8 weeks. Chronic
      consumption of 30% fructose solution led to a significant increase in hepatic
      steatosis and inflammation as well as plasma alanine-aminotransferase levels in
      wild-type mice. This effect of fructose feeding was markedly attenuated in iNOS(
      /-) mice. Hepatic lipidperoxidation, concentration of phospho-IkappaB, nuclear
      factor kappaB activity, and tumor necrosis factor-alpha mRNA level were
      significantly increased in fructose-fed wild-type mice, whereas in livers of
      fructose-fed iNOS(-/-) mice, lipidperoxidation, phospho-IkappaB, nuclear factor
      kappaB activity, and tumor necrosis factor-alpha expression were almost at the
      level of controls. However, portal endotoxin levels and hepatic myeloid
      differentiation factor 88 expression were significantly higher in both fructose
      fed groups compared to controls. Taken together, these data suggest that (i) the
      formation of reactive oxygen species in liver is a key factor in the onset of
      fatty liver and (ii) iNOS is involved in mediating the endotoxin/toll-like
      receptor 4-dependent effects in the development of fructose-induced fatty liver.

PMID- 21083423
TI  - Sulfiredoxin protects mice from lipopolysaccharide-induced endotoxic shock.
AB  - Peroxiredoxins constitute a major family of cysteine-based peroxide-scavenging
      enzymes. They carry an intriguing redox switch by undergoing substrate-mediated
      inactivation via overoxidation of their catalytic cysteine to the sulfinic acid
      form that is reverted by reduction catalyzed by the sulfinic acid reductase
      sulfiredoxin (Srx). The biological significance of such inactivation is not
      understood, nor is the function of Srx1. To address this question, we generated a
      mouse line with a null deletion of the Srx1-encoding Srxn1 gene. We show here
      that Srxn1(-/-) mice are perfectly viable and do not suffer from any apparent
      defects under laboratory conditions, but have an abnormal response to
      lipopolysaccharide that manifests by increased mortality during endotoxic shock.
      Microarray-based mRNA profiles show that although the response of Srxn1(-/-) mice
      to lipopolysaccharide is typical, spanning all spectrum and all pathways of
      innate immunity, it is delayed by several hours and remains intense when the
      response of Srxn1(+/+) mice has already dissipated. These data indicate that Srx1
      activity protects mice from the lethality of endotoxic shock, adding this enzyme
      to other host factors, as NRF2 and peroxiredoxin 2, which by regulating cellular
      reactive oxygen species levels act as important modifiers in the pathogenesis of
      sepsis.

PMID- 21083422
TI  - Disruption of pyridine nucleotide redox status during oxidative challenge at
      normal and low-glucose states: implications for cellular adenosine triphosphate,
      mitochondrial respiratory activity, and reducing capacity in colon epithelial
      cells.
AB  - We recently demonstrated that menadione (MQ), a redox cycling quinone, mediated
      the loss of mitochondrial glutathione/glutathione disulfide redox balance. In
      this study, we showed that MQ significantly disrupted cellular pyridine
      nucleotide (NAD(+)/NADH, NADP(+)/NADPH) redox balance that compromised cellular
      ATP, mitochondrial respiratory activity, and NADPH-dependent reducing capacity in
      colonic epithelial cells, a scenario that was exaggerated by low glucose. In the
      cytosol, MQ induced NAD(+) loss concurrent with increased NADP(+) and NAD kinase
      activity, but decreased NADPH. In the mitochondria, NADH loss occurred in
      conjunction with increased nicotinamide nucleotide transhydrogenase activity and
      NADP(+), and decreased NADPH. These results are consistent with cytosolic NAD(+)
      to-NADP(+) and mitochondrial NADH-to-NADPH shifts, but compromised NADPH
      availability. Thus, despite the sacrifice of NAD(+)/NADH in favor of NADPH
      generation, steady-state NADPH levels were not maintained during MQ challenge.
      Impairments of cellular bioenergetics were evidenced by ATP losses and increased
      mitochondrial O(2) dependence of pyridine nucleotide oxidation-reduction; half
      maximal oxidation (P(50)) was 10-fold higher in low glucose, which was lowered by
      glutamate or succinate supplementation. This exaggerated O(2) dependence is
      consistent with increased O(2) diversion to nonmitochondrial O(2) consumption by
      MQ-semiquinone redox cycling secondary to decreased NADPH-dependent MQ
      detoxication at low glucose, a situation that was corrected by glucose-sparing
      mitochondrial substrates.

PMID- 21083424
TI  - Stimulation of alpha7 nicotinic acetylcholine receptor by nicotine attenuates
      inflammatory response in macrophages and improves survival in experimental model
      of sepsis through heme oxygenase-1 induction.
AB  - Activation of nicotinic acetylcholine receptor alpha7 subunit (alpha7nAChR) by
      nicotine leads to the improved survival rate in experimental model of sepsis.
      Previously, we demonstrated that heme oxygenase (HO)-1 inducers or carbon
      monoxide significantly increased survival of lipopolysaccharide (LPS)-induced and
      cecal ligation and puncture-induced septic mice by reduction of high mobility
      group box 1 release, a late mediator of sepsis. However, that activation of
      alpha7nAChR by nicotine provides anti-inflammatory action through HO-1
      upregulation has not been elucidated. Here we show that HO-1-inducible effect by
      nicotine was mediated through sequential event-Ca(2+) influx, classical protein
      kinase C activation, and reactive oxygen species production-which activates
      phosphoinositol-3-kinase/Akt/Nrf-2 pathway. In addition, HO-1 is required for
      nicotine-mediated suppression of tumor necrosis factor-alpha, inducible nitric
      oxide synthase, and high mobility group box 1 expression induced by LPS in
      macrophages, as evidenced by the fact that nicotine failed to inhibit production
      of these mediators when HO-1 was suppressed. Importantly, nicotine-induced
      survival rate was reduced by inhibition of HO-1 in LPS- and cecal ligation and
      puncture-treated septic mice. Collectively, these data suggest that activation of
      alpha7nAChR by nicotine is critical in the regulation of anti-inflammatory
      process, which could be mediated through HO-1 expression. Thus, we conclude that
      activation of alpha7nAChR by nicotine provides anti-inflammatory action through
      HO-1 upregulation.

PMID- 21083425
TI  - Current good manufacturing practice production of an oncolytic recombinant
      vesicular stomatitis viral vector for cancer treatment.
AB  - Vesicular stomatitis virus (VSV) is an oncolytic virus currently being
      investigated as a promising tool to treat cancer because of its ability to
      selectively replicate in cancer cells. To enhance the oncolytic property of the
      nonpathologic laboratory strain of VSV, we generated a recombinant vector
      [rVSV(MDelta51)-M3] expressing murine gammaherpesvirus M3, a secreted viral
      chemokine-binding protein that binds to a broad range of mammalian chemokines
      with high affinity. As previously reported, when rVSV(MDelta51)-M3 was used in an
      orthotopic model of hepatocellular carcinoma (HCC) in rats, it suppressed
      inflammatory cell migration to the virus-infected tumor site, which allowed for
      enhanced intratumoral virus replication leading to increased tumor necrosis and
      substantially prolonged survival. These encouraging results led to the
      development of this vector for clinical translation in patients with HCC.
      However, a scalable current Good Manufacturing Practice (cGMP)-compliant
      manufacturing process has not been described for this vector. To produce the
      quantities of high-titer virus required for clinical trials, a process that is
      amenable to GMP manufacturing and scale-up was developed. We describe here a
      large-scale (50-liter) vector production process capable of achieving crude
      titers on the order of 10(9) plaque-forming units (PFU)/ml under cGMP. This
      process was used to generate a master virus seed stock and a clinical lot of the
      clinical trial agent under cGMP with an infectious viral titer of approximately 2
      * 10(10) PFU/ml (total yield, 1 * 10(13) PFU). The lot has passed all U.S. Food
      and Drug Administration-mandated release testing and will be used in a phase 1
      clinical translational trial in patients with advanced HCC.

PMID- 21083426
TI  - Rational design of murine secreted alkaline phosphatase for enhanced performance
      as a reporter gene in mouse gene therapy preclinical studies.
AB  - Many preclinical gene therapy studies use a reporter gene to evaluate vector
      design and performance in mouse models of human disease. Unfortunately, most
      commonly used reporter genes are immunogenic in mice, which confounds accurate
      evaluation of vector function. In previous studies, we showed that the murine
      secreted alkaline phosphatase (mSEAP) gene functions well as a simple and
      sensitive reporter gene in mice. In this study, we have used rational design to
      enhance mSEAP performance. The majority of native mSEAP remains attached to the
      outer surface of the cell through glycan phosphatidylinositol linkage; removal of
      the carboxy-terminal tail of mSEAP resulted in a dramatic enhancement of release
      of the protein into cell culture medium and into mouse plasma in whole animal
      experiments. We increased the heat stability of mSEAP through mutation of a key
      residue in the crown domain of the protein (H451E), thus allowing us to reduce
      endogenous, background AP activity through heat inactivation for enhanced
      sensitivity. We show that these alterations in mSEAP result in enhanced
      performance in tissue culture and mouse studies. Taken together, these data
      illustrate that mSEAP is a sensitive, nonimmunogenic reporter for preclinical
      mouse studies.

PMID- 21083427
TI  - Identification of potentially neuroprotective genes upregulated by neurotrophin
      treatment of CA3 neurons in the injured brain.
AB  - Specific neurotrophic factors mediate histological and/or functional improvement
      in animal models of traumatic brain injury (TBI). In previous work, several lines
      of evidence indicated that the mammalian neurotrophin NT-4/5 is neuroprotective
      for hippocampal CA3 pyramidal neurons after experimental TBI. We hypothesized
      that NT-4/5 neuroprotection is mediated by changes in the expression of specific
      sets of genes, and that NT-4/5-regulated genes are potential therapeutic targets
      for blocking delayed neuronal death after TBI. In this study, we performed
      transcription profiling analysis of CA3 neurons to identify genes regulated by
      lateral fluid percussion injury, or by treatment with the trkB ligands NT-4/5 or
      brain-derived neurotrophic factor (BDNF). The results indicate extensive overlap
      between genes upregulated by neurotrophins and genes upregulated by injury,
      suggesting that the mechanism behind neurotrophin neuroprotection may mimic the
      brain's endogenous protective response. A subset of genes selected for further
      study in vitro exhibited neuroprotection against glutamate excitotoxicity. The
      neuroprotective genes identified in this study were upregulated at 30 h post
      injury, and are thus expected to act during a clinically useful time frame of
      hours to days after injury. Modulation of these factors and pathways by genetic
      manipulation or small molecules may confer hippocampal neuroprotection in vivo in
      preclinical models of TBI.

PMID- 21083428
TI  - Differential Hox expression in murine embryonic stem cell models of normal and
      malignant hematopoiesis.
AB  - The Hox family are master transcriptional regulators of developmental processes,
      including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4),
      and Meis1, along with several individual Hox proteins, are implicated in stem
      cell expansion during embryonic development, with gene dosage playing a
      significant role in the overall function of the integrated Hox network. To
      investigate the role of this network in normal and aberrant, early hematopoiesis,
      we employed an in vitro embryonic stem cell differentiation system, which
      recapitulates mouse developmental hematopoiesis. Expression profiles of Hox,
      Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic
      differentiation process and compared with the effects of expressing the leukemic
      oncogene Tel/PDGFRbeta. During normal differentiation the Hoxa cluster, Pbx1 and
      Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39)
      and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa
      cluster genes (a9, a10, a11, and a13) maintained or increased expression at the
      hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7
      and a9, were differentially expressed after short-term oncogenic (Tel/PDGFRbeta)
      induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic
      driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1,
      and Pbx have previously been implicated in regulating target genes involved in
      hematopoietic stem cell (HSC) expansion and leukemic progression. These results
      provide direct evidence that transcriptional flux through the Hox network occurs
      at very early stages during hematopoietic differentiation and validates embryonic
      stem cell models for gaining insights into the genetic regulation of normal and
      malignant hematopoiesis.

PMID- 21083430
TI  - Dormant phase and multinuclear cells: two key phenomena in early culture of
      murine bone marrow mesenchymal stem cells.
AB  - Special features of mesenchymal stem cells (MSCs) have made them a popular tool
      in cell therapy and tissue engineering. Although mouse animal models and murine
      MSCs are common tools in this field, our understanding of the effect of in vitro
      expansion on the behavior of these cells is poor and controversial. In addition,
      in comparison to human, isolation of MSCs from mouse has been reported to be more
      difficult and some unexplained features such as heterogeneity and slow growth
      rate in the culture of these cells have been observed. Here we followed mouse
      bone marrow MSCs for >1 year after isolation and examined the effect of expansion
      on changes in morphology, growth kinetics, plasticity, and chromosomal structure
      during in vitro culture. Shortly after isolation, the growth rate of the cells
      decreased until they stopped dividing and entered a dormant state. In this state
      the size of the cells increased and they became multinuclear. These large
      multinuclear cells then gave origin to small mononuclear cells, which after a
      while resumed proliferation and could be expanded immortally. The immortal cells
      had diminished plasticity and were aneuploid but could not form tumors in nude
      mice. These results suggest that mouse bone marrow MSCs bear several
      modifications when expanded in vitro, and therefore, the interpretation of the
      data obtained with these cells should be done more cautiously.

PMID- 21083429
TI  - SIRT1 deficiency downregulates PTEN/JNK/FOXO1 pathway to block reactive oxygen
      species-induced apoptosis in mouse embryonic stem cells.
AB  - Silent mating type information regulation 2 homolog 1 (SIRT1) plays a critical
      role in reactive oxygen species-triggered apoptosis in mouse embryonic stem (mES)
      cells. Here, we investigated a possible role for the PTEN/Akt/JNK pathway in the
      SIRT1-mediated apoptosis pathway in mES cells. Akt was activated by removal of
      anti-oxidant 2-mercaptoethanol in SIRT1(-/-) mES cells. Since PTEN is a negative
      regulator of Akt and its activity can be modulated by acetylation, we
      investigated if SIRT1 deacetylated PTEN to downregulate Akt to trigger apoptosis
      in anti-oxidant-free culture conditions. PTEN was hyperacetylated and excluded
      from the nucleus in SIRT1(-/-) mES cells, consistent with enhanced Akt activity.
      SIRT1 deficiency enhanced the acetylation/phosphorylation level of FOXO1 and
      subsequently inhibited the nuclear localization of FOXO1. Cellular acetylation
      levels were enhanced by DNA-damaging agent, not by removal of anti-oxidant. c-Jun
      NH2-terminal kinase (JNK) was activated by removal of anti-oxidant in SIRT1
      dependent manner. Although p53 acetylation was stronger in SIRT1(-/-) mES cells,
      DNA-damaging stress activated phosphorylation and enhanced cellular levels of p53
      irrespective of SIRT1, whereas removal of anti-oxidant slightly activated p53
      only with SIRT1. Expression levels of Bim and Puma were increased in anti-oxidant
      free culture conditions in an SIRT1-dependent manner and treatment with JNK
      inhibitor blocked induction of Bim expression. DNA-damaging agent activated
      caspase3 regardless of SIRT1. Our data support an important role for SIRT1 in
      preparing the PTEN/JNK/FOXO1 pathway to respond to cellular reactive oxygen
      species.

PMID- 21083431
TI  - A multi-mode shock tube for investigation of blast-induced traumatic brain
      injury.
AB  - Blast-induced mild traumatic brain injury (bTBI) has become increasingly common
      in recent military conflicts. The mechanisms by which non-impact blast exposure
      results in bTBI are incompletely understood. Current small animal bTBI models
      predominantly utilize compressed air-driven membrane rupture as their blast wave
      source, while large animal models use chemical explosives. The pressure-time
      signature of each blast mode is unique, making it difficult to evaluate the
      contributions of the different components of the blast wave to bTBI when using a
      single blast source. We utilized a multi-mode shock tube, the McMillan blast
      device, capable of utilizing compressed air- and compressed helium-driven
      membrane rupture, and the explosives oxyhydrogen and
      cyclotrimethylenetrinitramine (RDX, the primary component of C-4 plastic
      explosives) as the driving source. At similar maximal blast overpressures, the
      positive pressure phase of compressed air-driven blasts was longer, and the
      positive impulse was greater, than those observed for shockwaves produced by
      other driving sources. Helium-driven shockwaves more closely resembled RDX
      blasts, but by displacing air created a hypoxic environment within the shock
      tube. Pressure-time traces from oxyhydrogen-driven shockwaves were very similar
      those produced by RDX, although they resulted in elevated carbon monoxide levels
      due to combustion of the polyethylene bag used to contain the gases within the
      shock tube prior to detonation. Rats exposed to compressed air-driven blasts had
      more pronounced vascular damage than those exposed to oxyhydrogen-driven blasts
      of the same peak overpressure, indicating that differences in blast wave
      characteristics other than peak overpressure may influence the extent of bTBI.
      Use of this multi-mode shock tube in small animal models will enable comparison
      of the extent of brain injury with the pressure-time signature produced using
      each blast mode, facilitating evaluation of the blast wave components
      contributing to bTBI.

PMID- 21083433
TI  - Effect of decompressive craniectomy on aquaporin-4 expression after lateral fluid
      percussion injury in rats.
AB  - Decompressive craniectomy is one therapeutic option for severe traumatic brain
      injury (TBI), and it has long been used for the treatment of patients with
      malignant post-traumatic brain edema. A lack of definitive evidence, however,
      prevents physicians from drawing any conclusions about the effects of
      decompressive craniectomy for the treatment of TBI. Therefore, the aim of the
      present study was to investigate the influence of decompressive craniectomy on
      post-traumatic brain edema formation. The aquaporin-4 (AQP4) water channel is
      predominantly expressed in astrocytes, and it plays an important role in the
      regulation of brain water homeostasis. In the present study, we investigated the
      time course of AQP4 expression and the water content of traumatized cortex
      following decompressive craniectomy after TBI. Adult male Sprague-Dawley rats
      (300-400 g) were subjected to lateral fluid percussion injury using the Dragonfly
      device. The effect of decompressive craniectomy was studied in traumatized rats
      without craniectomy (closed skull, DC-), and in rats craniectomized immediately
      after trauma (DC+). AQP4 expression was investigated with a Western blot analysis
      and immunohistochemistry. Brain edema was measured using the wet weight/dry
      weight method. At 48 h after TBI, AQP4 expression of the DC- group was
      significantly increased compared with the DC+ group (p < 0.01). In addition, the
      cortical water content of the DC- group was significantly increased compared to
      the DC+ group at the same time point (p < 0.05). The present results suggest that
      decompressive craniectomy may affect AQP4 expression and reduce brain edema
      formation after TBI.

PMID- 21083432
TI  - Activity-dependent increase in neurotrophic factors is associated with an
      enhanced modulation of spinal reflexes after spinal cord injury.
AB  - Activity-based therapies such as passive bicycling and step-training on a
      treadmill contribute to motor recovery after spinal cord injury (SCI), leading to
      a greater number of steps performed, improved gait kinematics, recovery of phase
      dependent modulation of spinal reflexes, and prevention of decrease in muscle
      mass. Both tasks consist of alternating movements that rhythmically stretch and
      shorten hindlimb muscles. However, the paralyzed hindlimbs are passively moved by
      a motorized apparatus during bike-training, whereas locomotor movements during
      step-training are generated by spinal networks triggered by afferent feedback.
      Our objective was to compare the task-dependent effect of bike- and step-training
      after SCI on physiological measures of spinal cord plasticity in relation to
      changes in levels of neurotrophic factors. Thirty adult female Sprague-Dawley
      rats underwent complete spinal transection at a low thoracic level (T12). The
      rats were assigned to one of three groups: bike-training, step-training, or no
      training. The exercise regimen consisted of 15 min/d, 5 days/week, for 4 weeks,
      beginning 5 days after SCI. During a terminal experiment, H-reflexes were
      recorded from interosseus foot muscles following stimulation of the tibial nerve
      at 0.3, 5, or 10 Hz. The animals were sacrificed and the spinal cords were
      harvested for Western blot analysis of the expression of neurotrophic factors in
      the lumbar spinal cord. We provide evidence that bike- and step-training
      significantly increase the levels of brain-derived neurotrophic factor (BDNF),
      neurotrophin-3 (NT-3), and NT-4 in the lumbar enlargement of SCI rats, whereas
      only step-training increased glial cell-derived neurotrophic factor (GDNF)
      levels. An increase in neurotrophic factor protein levels that positively
      correlated with the recovery of H-reflex frequency-dependent depression suggests
      a role for neurotrophic factors in reflex normalization.

PMID- 21083434
TI  - Near full-length genomic characterization of a novel HIV type 1 CRF07_ BC/CRF08_
      BC recombinant strain from Yunnan, China.
AB  - Yunnan province was considered the HIV-1 epicenter of China, where many subtypes
      and CRFs of HIV-1 were circulating. CRF07_BC and CRF08_BC were two of the main
      circulating subtypes that caused more than 90% of the HIV-1 infections in
      intravenous drug users (IDUs) in this district. The cocirculation of these two
      CRFs in the same area and population predicted the emergence of new second
      generation recombinants. This study presented a near full-length genomic analysis
      of a novel HIV-1 recombination (09YN072) involving CRF07_BC and CRF08_BC. The
      analyses of the sequence of 09YN072 showed that two CRF07_BC segments were
      inserted into the CRF08_BC backbone. The discovery of the novel recombinant
      strain complicates the HIV-1 epidemic in Yunnan, China, as well as the
      development of effective vaccines to limit the spread of HIV-1 in China.

PMID- 21083436
TI  - Microcarriers and their potential in tissue regeneration.
AB  - Microcarriers are a versatile tool with applications across a wide range of
      disciplines within tissue engineering. Large numbers of cells of appropriate
      phenotypes are required in engineering the many different tissues of the body,
      and microcarriers facilitate not only the expansion of many cell types but also
      the investigation of cell behavior in vitro. Microcarriers can also be used to
      directly deliver cells in vivo to repair and regenerate tissues. This review
      summarizes and discusses the use of microcarriers in diverse applications of
      tissue repair, including bone, cartilage, skin, vascular, central nervous system,
      adipose tissue, and liver repair. It also considers how microcarriers can be used
      to bulk-culture and deliver stem cells for tissue regeneration. Microcarriers
      thus have multidisciplinary use and advances in their use are of benefit to the
      entire tissue engineering field.

PMID- 21083435
TI  - Accumulation of P(T/S)AP late domain duplications in HIV type 1 subtypes B, C,
      and F derived from individuals failing ARV therapy and ARV drug-naive patients.
AB  - HIV-1 budding requires short peptide motifs in p6(Gag), known as late domains,
      that promote the release of infectious virions. The primary late domain of HIV-1
      is a Pro-(Thr/Ser)-Ala-Pro (hereafter referred to as a PTAP) motif. This motif
      may be completely or partially duplicated. In this work we analyzed p6(Gag)
      sequences from 547 isolates from drug-naive patients and 213 isolates from
      patients failing HAART therapy. Complete duplications within PTAP were selected
      during HAART therapy in all HIV-1 subtypes analyzed: B (p = 0.0338), F1 (p =
      0.0294), and C (p = 0.0001). Nevertheless, the patterns of these duplications
      were different; subtype C isolates accumulated longer duplications and displayed
      a higher frequency of duplications in both treated (54%) and drug-naive isolates
      (23%). Accumulation of PTAP duplications within subtypes B, F1, and C during
      therapy suggests a potential role of the duplications in antiretroviral drug
      resistance.

PMID- 21083437
TI  - Short communication: enhancement of immunogenicity of replication-defective
      adenovirus-based human immunodeficiency virus vaccines in rhesus monkeys.
AB  - Adenovirus (Ad) is still under extensive investigation as a vector for HIV
      vaccination; however, one possible explanation for the failure of Merck's STEP
      trial is the relatively weak immunogenicity of replication-defective Ad vectors.
      In this study, a novel strategy to enhance the immunogenicity of replication
      defective Ad-based HIV vaccines was developed. First, a recombinant plasmid
      expressing adenoviral E1 protein (pVAX-E1) was constructed to complement the E1
      deleted replication-defective Ad vectors in trans. Then, the immunogenicity of
      the vaccine regimen of Ad5-HIV gag plus pVAX-E1 plasmid was assessed in rhesus
      macaques. Compared with traditional administration of Ad-based vectors alone, the
      results showed that our strategy elicited a more sustained and robust HIV gag
      specific cellular response and enhanced long-term proliferation of CD4(+) and
      CD8(+) T lymphocytes. This strategy represents a proof-of-concept that enhances
      the immunogenicity of replication-defective Ad-based vectors, and it exemplifies
      the useful implications for Ad-based HIV vaccines and other vaccines.

PMID- 21083438
TI  - Hydrogel-electrospun mesh composites for coronary artery bypass grafts.
AB  - The aim of the present study was to investigate the potential of hydrogel
      electrospun mesh hybrid scaffolds as coronary artery bypass grafts. The
      circumferential mechanical properties of blood vessels modulate a broad range of
      phenomena, including vessel stress and mass transport, which, in turn, have a
      critical impact on cardiovascular function. Thus, coronary artery bypass grafts
      should mimic key features of the nonlinear stress-strain behavior characteristic
      of coronary arteries. In native arteries, this J-shaped circumferential stress
      strain curve arises primarily from initial load transfer to low stiffness elastic
      fibers followed by progressive recruitment and tensing of higher stiffness
      arterial collagen fibers. This nonlinear mechanical response is difficult to
      achieve with a single-component scaffold while simultaneously meeting the suture
      retention strength and tensile strength requirements of an implantable graft. For
      instance, although electrospun scaffolds have a number of advantages for arterial
      tissue engineering, including relatively high tensile strengths, tubular mesh
      constructs formed by conventional electrospinning methods do not generally
      display biphasic stress-strain curves. In the present work, we demonstrate that a
      multicomponent scaffold comprised of polyurethane electrospun mesh layers
      (intended to mimic the role of arterial collagen fibers) bonded together by a
      fibrin hydrogel matrix (designed to mimic the role of arterial elastic fibers)
      results in a composite construct which retains the high tensile strength and
      suture retention strength of electrospun mesh but which displays a J-shaped
      mechanical response similar to that of native coronary artery. Moreover, we show
      that these hybrid constructs support cell infiltration and extracellular matrix
      accumulation following 12-day exposure to continuous cyclic distension.

PMID- 21083439
TI  - Cross-sectional study of biomarkers of exposure and biological effect on
      monozygotic twins discordant for smoking.
AB  - BACKGROUND: The aim of this study was to investigate the possible correlation
      between smoking status and biomarkers of exposure (BoE) and biological effect
      (BoBE) in monozygotic twins discordant for smoking status (smoker and non-smoker
      pairs). By eliminating potential genetic variability in this manner, a clearer
      pattern of the effects of lifestyle and environmental exposures should become
      apparent. METHODS: This was a cross-sectional study on monozygotic healthy twins
      (44 subjects, 26 males and 18 females) with a mean age 31.5 years. BoE to
      cigarette smoke and BoBE were measured in body fluids (24 h urine and blood)
      after medical pre-screening. RESULTS: All BoE were significantly higher in the
      smoker twins. Among BoBE, 11-dehydrothromboxane B(2) (11-dehydro TBX), 2,3
      dinorthromboxane B(2) (2,3-dinor TBX), 8-epi-prostaglandin F2alpha (8-epiPGF),
      hydroxyproline (OH-P), fibrinogen, white blood cell (WBC), neutrophil and
      lymphocyte counts and heart rate were statistically significantly increased in
      the smoker compared to the non-smoker twins. Moreover, statistically significant
      correlations between neutrophil count and 11-dehydro TBX (r=0.32), WBC and 8
      epiPGF (r=0.33), OH-P and 8-epiPGF (r=0.49) and heart rate and fibrinogen
      (r=0.46) were observed. CONCLUSIONS: The study results confirmed the reliability
      of the BoE for the evaluation of smoking status. Moreover, a subset of the BoBE,
      reported as being associated with inflammatory conditions and early stages of
      vascular disorders, has emerged as showing a consistent relationship with smoking
      status from the present and the previous studies. By using monozygotic twin
      pairs, genetic variability has been excluded as a possible source of variability
      in this study. These results should assist in the interpretation of other
      population studies using these biomarkers.

PMID- 21083440
TI  - A high-performance liquid chromatographic method for benznidazole quantitation in
      plasma of patients with Chagas disease.
AB  - BACKGROUND: Chagas disease is endemic in Latin America, affecting 16-18 million
      people with more than 100 million exposed to risk of infection. Its etiological
      agent is Trypanosoma cruzi. To date, benznidazole is the only treatment of Chagas
      disease available in Europe. METHODS: A high-performance reversed-phase isocratic
      liquid chromatographic method for benznidazole analysis in human plasma is
      described. The mobile phase consists of 60% ultrafiltered water and 40%
      acetonitrile. Samples were precipitated with trichloroacetic acid (0.3 M) (1/1,
      v/v). The injection volume was 100 MUL. Benzocaine was used as internal standard.
      RESULTS: The assay was linear over a benznidazole concentration range of 1.6-100
      MUg/mL. The method showed good agreement of results (n=15): inaccuracy (5.6%),
      intra- and inter-day variability (1.1% and 3.9%, respectively), recovery (94.9%),
      limit of detection (0.8 MUg/mL), lower limit of quantitation (1.6 MUg/mL) and
      acceptable stability over 24 h in the auto-sampler. Only 25 samples (58%) showed
      values within the therapeutic range. Three samples were subtherapeutic and 15
      were in the toxic range. CONCLUSIONS: The method offers a fast and simple
      approach to determining benznidazole in human plasma which could be of use in
      pharmacokinetic and safety studies.

PMID- 21083441
TI  - Ischemia modified albumin changes - review and clinical implications.
AB  - Ischemia modified albumin (IMA), as measured using the albumin cobalt binding
      test, is currently the most promising biomarker for early detection of ischemia
      before the onset of irreversible cardiac injury. This paper reviews the
      information available on IMA, including its pathophysiology, analysis, clinical
      applications and future perspectives. The data provided was identified by a
      search of MEDLINE using the terms IMA, biomarkers and ischemia. IMA may be useful
      to cover the complete diagnostic window of patients presenting with acute
      coronary syndromes (ACS) in the Emergency Department, along with the
      electrocardiogram and cardiac troponins. Preliminary data regarding the
      significance of IMA in the prognosis of either ACS or following revascularization
      need further study.

PMID- 21083442
TI  - Analytical validation of the Liaison Calcitonin_II-Gen (DiaSorin).
AB  - BACKGROUND: We validated the DiaSorin Liaison Calcitonin_II-Gen, an improved
      method for calcitonin (CT) measurements, compared this method with the Cisbio_h
      CT kit and established the reference range of CT in a normal adult population.
      METHODS: We determined the precision, functional sensitivity, traceability to the
      2nd IS 89/620, linearity and measurement uncertainty, accuracy profile and beta
      expectation limits. We evaluated the specificity, the susceptibility to human
      anti-animal antibodies (HAMA), hook-effect and carry over. To establish a
      reference range, we selected 267 adults without renal insufficiency presenting
      with normal thyroid stimulating hormone (TSH), free thyroxin (T4) and calcium
      concentrations and without anti-thyroglobulin antibodies as our "reference"
      healthy population. We compared the method with Cisbio on 250 consecutive and 45
      samples from a post-pentagastrin stimulation test. RESULTS: Precision (expressed
      as CV) was < 10% for the measurement range, functional sensitivity: 5.3 ng/L and
      the method was found linear until to a 1/10 dilution. Uncertainty ranged from 25%
      to 7.2%, and the risk that one result falls out of the +/- 20% acceptance limits
      was < 5% between 2.9 and 1513 ng/L. The Bland and Altman plot showed no
      systematic bias between the two methods. The test is still prone to HAMA
      influence, does not present any hook-effect, although carry over was observed.
      Ninety-five percent of our adult reference population showed CT concentrations <
      7.4 ng/L, with an important gender difference: 95% of the men showed CT values <
      9.8 ng/L, whereas 95% of women were < 4.0 ng/L. CONCLUSIONS: The Liaison
      Calcitonin_II-Gen is an analytically robust method. The important difference in
      gender observed in our population might lead to re-evaluation of the generally
      used "10 ng/L" cut-off in a multicentre prospective study.

PMID- 21083443
TI  - Hyperhemolysis syndrome in sickle cell disease.

PMID- 21083445
TI  - Azacitidine: activity and efficacy as an epigenetic treatment of myelodysplastic
      syndromes.
AB  - 5'-azacitidine is a ring analog of cytosine, differing from the natural
      nucleoside because it has a nitrogen in lieu of carbon in position five of the
      pyrimidine. Despite being synthesized approximately 40 years ago it has only
      recently been employed with success at low doses in the treatment of
      myelodysplastic syndromes (MDS). This drug has hypomethylating activity and,
      possibly, exerts its action by reinducing expression of genes silenced by the
      hypermethylation of CpG islands in their promoters. Azacitidine is administered
      prevalently subcutaneously (75 mg/m(2)/day for 7 days every 28 days) as the
      pharmacokinetics and pharmacoavailability are almost equivalent to the
      intravenous route. It was the first agent demonstrated to delay acute
      myeloblastic leukemia transformation and to prolong survival for patients with
      higher risk MDS, and it was approved in 2004 by the US FDA for treatment of all
      MDS risk categories. Azacitidine allows transfusion independence in more than 40%
      of treated MDS patients, and has opened a new era in the treatment of MDS and the
      use of 'epigenetic drugs'. To correctly use this agent and obtain hematological
      improvements that lead to a prolonged overall survival of MDS patients,
      hematologists have to modify their perspective and their usual expectations from
      a chemotherapy-like regimen. Azacitidine may also be administered quite safely to
      elderly patients presenting comorbidities and it is well tolerated in an out
      patient regimen. Its mode of action does not necessarily require cytotoxicity and
      does not induce a rapid response. Several rounds of therapy and of consequent
      hypomethylation of target genes are necessary to re-express silenced genes
      critical to differentiation and the majority of patients will respond after three
      to six cycles of therapy.

PMID- 21083446
TI  - Communications on multiple myeloma.
AB  - The following report will focus on nine important presentations given during the
      50th annual meeting of the American Society of Hematology. Interesting new data
      on the latest drugs, treatment of patients younger or older than 65 years, and
      new combinations were discussed.

PMID- 21083447
TI  - Oncogenic Kras and Notch-1 cooperate in T-cell acute lymphoblastic
      leukemia/lymphoma.
AB  - Mutations of the Ras family are one of the most common somatic events found in
      all human cancers, although they are relatively rare in T-cell acute
      lymphoblastic leukemia (T-ALL). In mice, conditional expression of oncogenic
      Kras(G12D) from its endogenous promoter causes a fatal myeloproliferative
      disorder, and only rarely a T-ALL-like disease. In the article being evaluated,
      the authors demonstrate that primary mice expressing oncogenic Kras have a block
      in T-cell differentiation at the double-negative 1 stage. Interestingly, most
      secondarily transplanted mice develop a fatal T-ALL-like disease. Sequencing of
      NOTCH-1 showed that 50% of these mice harbored truncating mutations in the PEST
      domain that would be predicted to activate Notch signaling. Cell lines
      established from some of the mice demonstrated sensitivity to gamma-secretase
      inhibition, suggesting that even when NOTCH-1 mutations occur as secondary
      collaborating events, tumors retain a dependency on this pathway that might be
      exploitable clinically.

PMID- 21083448
TI  - Renin-angiotensin system and hemangioblast development from human embryonic stem
      cells.
AB  - Human embryonic stem cells (hESCs) offer the opportunity to create a novel source
      of blood cells for transfusion, transplantation and cancer immunotherapy.
      Identification of sequential progenitors leading to blood development, as well as
      a detailed understanding of the molecular mechanisms of hematopoietic lineage
      specification and diversification from hESCs, will be critical to advance
      technologies for large-scale production of blood cells and in vitro generation of
      hematopoietic stem cells. Multiple lines of evidence suggest that hematopoiesis,
      both in vivo during embryogenesis and in vitro from hESCs, is initiated from
      hemangioblasts; cells with the potential to generate both hematopoietic and
      endothelial cells. However, the phenotypic and functional properties of
      hemangioblasts remain largely unknown. The paper from Zambidis et al. is the
      first demonstration that hemangioblasts generated from hESCs express angiotensin
      converting enzyme (CD143). More importantly, the current study demonstrates that
      the renin-angiotensin system plays a critical role in the hemangioblast fate
      decision to produce either blood or endothelial cells. These findings could be
      exploited for developing novel cellular and drug therapies for hematological and
      vascular diseases.

PMID- 21083449
TI  - Myeloid growth factors as anti-infective measures in children with leukemia and
      lymphoma.
AB  - Clinical trials in children treated for leukemia and lymphoma demonstrated that
      the hematopoietic colony-stimulating factors (CSFs) granulocyte (G) and
      granulocyte-macrophage (GM) CSFs ameliorate duration and depth of neutropenia,
      and also seem to decrease antibiotic usage and hospitalization. However, neither
      G-CSF nor GM-CSF significantly reduced the risk for infectious complications,
      such as febrile neutropenia or documented infections, or improved overall
      survival in these patient populations. Since it is unclear whether G- and GM-CSF
      may increase the risk for relapse in subgroups of patients with leukemia,
      guidelines recommend that hematopoietic growth factors should be used with
      caution in children with leukemia and lymphoma.

PMID- 21083450
TI  - Therapeutic approaches to non-Hodgkin's lymphoma in the elderly patient.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) is increasing among all age groups,
      with a median age at diagnosis of 67 years. With the increase in the geriatric
      population, there is a need for the development and validation of treatment
      strategies for NHL for these patients. Therapy in elderly patients is affected by
      multiple factors, especially comorbidities. Over the past decade, some treatment
      trials have included older patients. The disease incidence, characteristics and
      treatment approaches for both follicular and diffuse aggressive NHL histologies
      in elderly patients are reviewed, as well as the impact of aging on the care of
      these patients.

PMID- 21083451
TI  - Preventing thrombophilia-related complications of pregnancy.
AB  - Pregnancy is associated with an increased risk of venous thromboembolism (VTE)
      and approximately half of all pregnancy-related VTEs are associated with
      thrombophilia. Recent studies suggest that there is a link between thrombophilia
      and other adverse pregnancy outcomes, such as fetal loss, preeclampsia, placental
      abruption and intrauterine growth restriction. However, the associations reported
      are modest, and high quality data are limited. Although the most compelling data
      derive from pregnant women with antiphospholipid antibodies, the use of
      anticoagulants for the prevention of pregnancy complications other than VTE in
      women with heritable thrombophilias is becoming more frequent. In this article,
      we review the impact of the various thrombophilias on pregnancy and its outcome,
      the evidence for therapies aimed at prevention of thrombophilia-related pregnancy
      complications, and briefly discuss the role of screening for thrombophilia in
      pregnancy.

PMID- 21083452
TI  - Umbilical cord blood: biology and transplantation.
AB  - Umbilical cord blood transplantation is becoming an acceptable alternative source
      of hematopoietic stem cells for patients with malignant diseases. Cord blood
      differs from bone marrow and peripheral blood progenitors in its immune tolerance
      and kinetics of engraftment. In this article, we will review the biology of cord
      blood stem cells and clinical studies of cord blood transplants in pediatric and
      adult populations. We will also discuss potential uses of cord blood stem cells
      in regenerative medicine and novel methods for ex vivo expansion of hematopoietic
      stem cells. As we learn more about cord blood transplants, there is the potential
      to overcome the limitations of cord blood transplants so that they can become
      more widely available.

PMID- 21083454
TI  - T-cell therapy: the next generation.

PMID- 21083456
TI  - Bendamustine: new perspective for an old drug in lymphoproliferative disorders.
AB  - Bendamustine is an old bifunctional alkylating agent that also has potential
      antimetabolite properties, and only partial cross-resistance with other
      alkylators. Although it was synthesized in 1963 only few validated study results
      exist from this early period. More recently, its peculiar mechanism of action has
      reawakened interest in this drug that has been extensively studied in indolent
      non-Hodgkin lymphoma (NHL) and in chronic lymphocytic leukemia (CLL). Experience
      has also been reported in high-grade NHL and Hodgkin disease. Based on its unique
      structure, various strategies can be used for mechanism-based combination
      chemotherapeutic regimens with bendamustine. Moreover, data indicates that
      bendamustine when combined with rituximab is a valid therapeutic choice for
      patients with CLL or low-grade NHL demonstrating refractoriness to standard
      chemotherapy regimens. Furthermore, its documented favorable toxicity profile
      makes it a particularly useful treatment option for elderly patients.

PMID- 21083457
TI  - Hemophilia: basic and translational science.
AB  - The following report will provide a brief overview of presentations provided
      during the Scientific Subcommittee on Hemostasis program at the 51st Annual
      Meeting of the American Society of Hematology, held in New Orleans (LA, USA) in
      December 2009. The topic of this year's subcommittee meeting was Hemophilia:
      Basic and Translational Science and was chaired by David Lillicrap from Queen's
      University, Canada. The session was held twice and three speakers covered a range
      of topics, including Factor VIII and the unfolded protein response, novel
      hemostatic bypassing molecules and wound healing in hemophilia.

PMID- 21083458
TI  - Hepcidin biology and therapeutic applications.
AB  - The hepatic peptide hormone hepcidin regulates plasma iron concentrations and
      tissue iron distribution by inhibiting dietary iron absorption and mobilization
      of iron from stores in macrophages and hepatocytes. Dysregulation of hepcidin
      production underlies many iron disorders. Deficient production of hepcidin causes
      systemic iron overload in hereditary hemochromatosis and iron-loading anemias,
      such as beta-thalassemia, whereas hepcidin excess contributes to the development
      of anemia in inflammatory disorders and chronic kidney disease, and may cause
      erythropoietin resistance. The Scientific Program on Iron and Heme session at the
      51st ASH annual meeting discussed recent advances in understanding hepcidin
      biology and explored the potential for hepcidin therapeutic applications. The
      session included three 30-min presentations.

PMID- 21083459
TI  - Targeted therapy of BCL6-dependent diffuse large B-cell lymphomas by heat-shock
      protein 90 inhibition.
AB  - Heat-shock protein (HSP)90 is a molecular chaperone involved in the proper
      folding and cellular transportation of many signaling proteins that are
      deregulated in lymphoma. HSP90 inhibition results in proteasomal degradation of
      these proteins, leading to antitumoral activity. Recent studies have focused on
      the use of HSP90 inhibitors as potential therapies for non-Hodgkin lymphoma. BCL6
      plays a critical role in the pathogenesis of most diffuse large B-cell lymphoma
      (DLBCL), the most frequent non-Hodgkin lymphoma. The current study demonstrates
      that HSP90 forms a complex with BCL6, and inhibition of HSP90 with the drug PU
      H71 selectively kills BCL6-positive DLBCL in animal models. These data support
      the use of HSP90 inhibitor PU-H71 for treating patients with BCL6-positive DLBCL.

PMID- 21083460
TI  - Prolonged and increased postoperative risk of venous thromboembolism: rationale
      for even more 'extended' prophylaxis?
AB  - It is well known that the risk of venous thromboembolism is increased after
      surgery; however, specific data on how long this risk lasts or how the risk
      varies by type of surgery is limited. The Million Women Study is a population
      based prospective study that recruited 1.3 million women through the National
      Health Service breast screening program. This study used data from the Million
      Women Study to examine the magnitude and the duration of the risk of venous
      thromboembolism after different types of surgery with a mean follow-up duration
      of 6.2 years. The risk was found to be higher and longer lasting than previously
      thought, with considerable variation among different types of surgery; therefore,
      raising important questions regarding the optimal duration of prophylaxis.

PMID- 21083461
TI  - Unique clinical and biological features of leukemia in Down syndrome children.
AB  - Acute leukemias in children with Down syndrome (DS) are characterized by unique
      clinical and biological features. Notable among DS children with acute myeloid
      leukemia (AML), is the high frequency of the acute megakaryocytic leukemia (AMkL)
      subtype, which uniformly harbor somatic mutations in the transcription factor
      GATA1 gene. DS patients with AML, and in particular AMkL, have event-free
      survival rates of 80-100% in contrast to event-free survival rates of less than
      35% for non-DS children with AMkL. DS children with acute lymphoblastic leukemia
      have a more heterogeneous disease, with approximately 30% of the patients having
      somatic JAK2 mutations, heightened methotrexate sensitivity and higher rates of
      treatment-related toxicities. These features highlight a striking relationship
      between genes localized to chromosome 21, leukemogenesis and sensitivity to
      leukemia chemotherapy agents.

PMID- 21083462
TI  - Emerging role of epigenetic therapies in cutaneous T-cell  lymphomas.
AB  - Cutaneous T-cell lymphomas (CTCLs) are rare lymphomas that arise primarily in the
      skin and are treated with skin-directed therapies in early-stage disease.
      Systemic therapy is indicated once skin-directed therapy is ineffective or for
      advanced-stage disease. CTCLs tend to be poorly responsive to chemotherapy and
      are incurable except for allogeneic stem cell transplantation. Recently, a new
      class of agents called histone deacetyalse inhibitors (HDACis) have shown
      remarkable activity in T-cell lymphomas in general and CTCLs in particular. Oral
      vorinostat and intravenous romidepsin are two HDACis that are now approved by the
      US FDA for use in patients with relapsed CTCLs. Several other HDACis are
      currently in clinical trials for CTCLs and other diseases and, although these
      agents vary by chemical structure and potency, the results of the ongoing
      clinical trials will eventually reveal if there are differences in clinical
      activity as well. The exact mechanism of action of these agents is unknown, but
      they are thought to affect the acetylation status of histones and other proteins
      in the cell and epigentically modulate transcription and other cellular
      activities. This leads to a myriad of downstream effects on cell cycle, apoptosis
      and differentiation. The following review summarizes the known biological
      mechanisms and clinical activity of various HDACis in the treatment of CTCLs and
      tries to define their role in the treatment paradigm of these unusual disorders.

PMID- 21083463
TI  - Iron-deficiency anemia secondary to mutations in genes controlling hepcidin.
AB  - The discovery of the peptide hormone hepcidin in 2001 has shed light on the
      control of iron metabolism. Studies in animal models over the past few years have
      demonstrated its key role in regulating iron homeostasis. It was found that
      hepcidin deficiency leads to iron overload, and that its overexpression leads to
      severe iron-deficiency anemia. Since then, other genes regulating hepcidin
      expression have been discovered, and defects in them mostly resulted in iron
      overload. In 2008, a new gene, TMPRSS6, was identified that encodes a negative
      regulator of hepcidin expression. This discovery has been of great relevance
      because TMPRSS6 is the first gene regulating hepcidin, mutations in which cause
      chronic iron-deficiency anemia. Recently, genome-wide association studies
      identified common TMPRSS6 variants associated with hematological parameters,
      suggesting that TMPRSS6 is crucial in the control of iron homeostasis and normal
      erythropoiesis.

PMID- 21083464
TI  - Current status of thrombopoietic agents.
AB  - Two different thrombopoietic drugs, romiplostim and eltrombopag, have completed
      Phase III trials in patients with immune-mediated thrombocytopenia and were
      observed to successfully improve platelet counts. This review will mostly focus
      on these two agents. We shall review their preclinical development as well as
      clinical trial results in immune-mediated thrombocytopenia. Also, we shall
      discuss their potential clinical use in thrombocytopenias associated with other
      medical conditions where reduction in platelet production is an integral part of
      disease manifestations.

PMID- 21083465
TI  - Novel oral anticoagulants for prophylaxis and treatment of venous
      thromboembolism: part I (Factor Xa inhibitors).
AB  - The quest for an ideal anticoagulant is ongoing. Oral agents that do not require
      blood level monitoring are presently undergoing taut scrutiny for efficacies and
      potential side effects, and would potentially soon revolutionize coagulation
      medicine. The first part of this article reviews oral Factor Xa inhibitors, such
      as rivaroxaban, apixaban, eribaxaban, edoxaban and YM150--exploring the outcomes
      of major clinical trials for prophylaxis and treatment of venous thromboembolism-
      and also briefly outlining their pharmacological properties. The second part of
      the article (in a separate issue) will cover oral Factor IIa (thrombin), such as
      dabigatran and AZD0837 and oral Factor IX inhibitors, such as TTP889.

PMID- 21083467
TI  - Neurocognitive function in sickle cell disease: have we been missing something?

PMID- 21083469
TI  - Pharmacology of argatroban.
AB  - Argatroban is a synthetic, small-molecule direct thrombin inhibitor that is
      approved in the USA, the EU and Japan for prophylaxis or treatment of thrombosis
      in patients with heparin-induced thrombocytopenia (HIT), and for anticoagulation
      of HIT patients undergoing PCI. Argatroban binds reversibly to, and inhibits both
      soluble and clot-bound thrombin. Argatroban does not generate antibodies, is not
      susceptible to degradation by proteases and is cleared hepatically. It has a
      predictable anticoagulant effect and there is a good correlation between dose,
      plasma concentration and pharmacodynamic effect. Initial clinical studies suggest
      that further investigations to establish the use of argatroban in ischemic
      stroke, acute coronary syndrome, hemodialysis, blood oxygenation, off-pump
      cardiac surgery and other clinical indications are warranted.

PMID- 21083471
TI  - Plasma cell leukemia: concepts and management.
AB  - Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia.
      Patients with PCL have a very poor prognosis with median survival measured in
      months. PCL can present de novo or following a prodrome of plasma cell myeloma.
      Patients with PCL tend to present with aggressive clinical features, such as
      extramedullary disease, bone marrow failure, advanced stage disease and
      expression of distinct immunophenotypic markers, such as lack of CD56 and
      presence of CD20. Historically, the treatment of PCL has primarily been
      palliative, with only a small minority of patients achieving a durable remission.
      The impact of newer agents, such as bortezomib and lenalidomide, in conjunction
      with autologous and allogeneic stem cell transplantation is uncertain, but
      emerging data suggest that use of these modalities may help improve the poor
      prognosis of patients with PCL.

PMID- 21083472
TI  - Many, but not all, outcome studies support exclusion of female plasma from the
      blood supply.
AB  - Transfusion-related acute lung injury (TRALI) has been identified as the most
      common cause of transfusion-related death. Although extensive literature supports
      restrictions on female-donor plasma to reduce antibody-mediated TRALI, only a few
      outcome studies have assessed for effects of this change, and some, but not all,
      have endorsed the policy. A recent report even suggests poorer outcomes in
      cardiac surgery patients with a shift to male-donor-only plasma, raising concerns
      that TRALI alone, whether catastrophic or more survivable, is insufficient
      compared with broader measures, such as short-term mortality or long-term
      survival, as an end point to assess for overall improvements in patient care.

PMID- 21083473
TI  - Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on
      screening and prevention.
AB  - Uncertainty regarding the pathophysiology of fetal and neonatal alloimmune
      thrombocytopenia (FNAIT) has hampered the decision regarding how to identify,
      follow-up and treat the women and children with this potentially serious
      condition. Since knowledge of the condition is derived mainly from retrospective
      studies, understanding of the natural history of this condition remains
      incomplete. General screening programs for FNAIT have still not been introduced,
      mainly because of a lack of reliable risk factors and effective treatment. Now,
      several prospective screening studies involving up to 100,000 pregnant women have
      been published and the results have changed the understanding of the
      pathophysiology of FNAIT and, thereby, the approach toward diagnostics,
      prevention and treatment in a more appropriate way.

PMID- 21083475
TI  - Prognostic factors in Hodgkin lymphoma.
AB  - Depending on stage and risk factor profile, up to 95% of patients with Hodgkin
      lymphoma at first presentation reach complete remission after the initial
      standard treatment including radiotherapy, combination chemotherapy or combined
      modality therapy. Patients who relapse after first complete remission can achieve
      a second complete remission and long-term disease-free survival with salvage
      treatment including radiotherapy for localized relapse in previously
      nonirradiated areas, conventional salvage chemotherapy, or high-dose chemotherapy
      with stem cell transplantation. In general, risk-adapted treatment strategies are
      used in the treatment of patients with Hodgkin lymphoma. Adequate staging of
      newly diagnosed patients enables optimal treatment planning, which is of
      particular importance for finding a balance between treatment efficacy and
      toxicity. In this review, an overview is given of the current knowledge of
      clinical and biological risk factors and the role of imaging modalities during
      and after treatment.

PMID- 21083474
TI  - Fondaparinux: does it cause HIT? Can it treat HIT?
AB  - Heparin-induced thrombocytopenia (HIT) is an antibody-mediated prothrombotic
      disorder triggered by PF4-binding polyanions, usually heparin. The
      pentasaccharide anticoagulant, fondaparinux, despite its negative charge and
      structural similarity to heparin, does not usually promote antibody binding to
      PF4 (owing to absent/weak 'cross-reactivity'). Thus, despite its ability to
      trigger anti-PF4/heparin antibodies ('immunogenicity'), fondaparinux has low -
      but not zero - risk of inducing HIT de novo, or of exacerbating HIT when
      antibodies are already present. Indeed, despite rare reports of fondaparinux
      induced HIT, this 'dissociation' between immunogenicity and cross-reactivity
      suggests that fondaparinux should be effective in treating HIT, as supported by
      several observational studies. An emerging issue: will clinicians accept this
      favorable experience of fondaparinux for treating HIT when a lack of randomized
      trials will hinder regulatory approval for this indication?

PMID- 21083476
TI  - Diagnosis and management of natural killer-cell malignancies.
AB  - Natural killer (NK)-cell malignancies are uncommon neoplasms, which have been
      referred to as polymorphic reticulosis or angiocentric T-cell lymphomas in the
      past. In the current WHO classification, they are categorized as extranodal NK/T
      cell lymphoma, nasal type and aggressive NK-cell leukemia. NK-cell malignancies
      show a geographical predilection for Asian and South American populations and are
      rare in the west. Pathologically, NK-cell lymphomas show a polymorphic neoplastic
      infiltrate with angioinvasion and angiodestruction. The lymphoma cells are
      CD2(+), cytoplasmic CD3epsilon(+) and CD56(+), with germline T-cell receptor
      gene. There is an almost invariable clonal episomal infection with Epstein-Barr
      virus. Clinically, NK-cell lymphomas can be classified into nasal, non-nasal and
      aggressive lymphoma/leukemia subtypes. Most nasal NK-cell lymphomas present with
      stage I/II disease. The early use of radiotherapy, either alone or
      concomitantly/sequentially with chemotherapy, is the most important factor in
      achieving successful treatment. Many stage I/II patients receiving radiotherapy
      alone fail systemically, so the use of chemotherapy is also considered necessary.
      Chemotherapy is indicated for stage III/IV nasal NK-cell lymphoma, and the non
      nasal and aggressive subtypes. Recent regimens that incorporate the use of L
      asparaginase have resulted in substantial improvements in outcome in high-risk,
      refractory or relapsed patients. High-dose chemotherapy and hematopoietic stem
      cell transplantation with autologous or allogeneic hematopoietic stem cells may
      be beneficial to selected patients. Prognostication of patients with clinical
      prognostic models and presentation circulating Epstein-Barr DNA load may be
      useful in the stratification of patients for various treatment modalities.

PMID- 21083477
TI  - Managing fungal and viral infections in pediatric leukemia.
AB  - Despite steadily improving long-term outcomes, infections remain a major cause of
      morbidity and mortality in children receiving therapy for leukemia. Standardized
      approaches to the management of bacterial infections have been highly successful.
      However, management of fungal and viral infections remains challenging,
      especially given the shifting epidemiology of fungal infections. Significant
      advances in diagnostic and therapeutic modalities have been achieved for fungal
      and viral infections over the past decade, providing new opportunities for
      effective interventions. This article reviews the management of viral and fungal
      infections in children undergoing therapy for leukemia.

PMID- 21083478
TI  - Immunotherapy against EBV-lymphoma in recipients of HSCT.
AB  - Epstein-Barr virus (EBV)-associated lymphoproliferations represent life
      threatening complications of hematopoietic stem cell transplantation. In the last
      decade, immunological therapeutic strategies that allow us to selectively
      abrogate the origin of lymphoproliferation, namely B-cell compartment or EBV
      antigen-expressing tumor cells, have significantly reduced treatment-related
      toxicity while maintaining equal or superior efficacy. A further implementation
      is the possibility of preventing disease occurrence by delivering immunotherapy
      in the presymptomatic phase, on the basis of EBV-DNA blood levels. Despite the
      excellent results, T-cell therapy with EBV-specific cytotoxic T-lymphocytes has
      but a marginal role in the treatment of these forms. Promising implementations
      are underway, including logistic solutions to extend T-cell therapy beyond
      academic centers, delineation of strategies aimed at simplifying/shortening
      production and targeting immune evasion mechanisms exerted by tumor cells.

PMID- 21083479
TI  - Treatment of graft-versus-host disease with monoclonal antibodies and related
      fusion proteins.
AB  - Allogeneic hematopoietic stem cell transplantation has evolved from an
      experimental treatment approach to a widely used, curative therapy to treat
      malignant and nonmalignant diseases of the hematopoietic system. Despite advances
      in donor selection, conditioning regimens and supportive care, acute and chronic
      graft-versus-host disease (GvHD) remain a major cause of morbidity and mortality.
      Steroids are the standard first-line treatment and are able to control GvHD in
      approximately 50% of patients. Those who fail on steroids have a poor long-term
      prognosis. Therefore, a large number of drugs and procedures have been evaluated
      as second-line therapy. Monoclonal antibodies have increasingly been used to
      treat malignancy and autoimmune disease during the last 20 years. Their unique
      ability to target specific antigens theoretically enables them to directly
      interfere with cellular mechanisms that are involved in GvHD pathology. For this
      reason, monoclonal antibodies have been studied extensively as a second-line
      treatment for acute and chronic GvHD. The purpose of this article is to collect
      published data on clinical trials from the current literature and to give an
      overview on efficacy and toxicity of monoclonal antibody treatment for GvHD.

PMID- 21083481
TI  - Dried blood spot sampling for quantitative bioanalysis: time for a revolution?

PMID- 21083482
TI  - The application of dried blood spot sampling in global clinical trials.

PMID- 21083483
TI  - Increasing efficiency for dried blood spot analysis: prospects for automation and
      simplified sample analysis.

PMID- 21083484
TI  - Pharmacokinetic considerations as to when to use dried blood spot sampling.
AB  - In the past few years there has been a large increase in the reporting of the use
      of dried blood spots (DBS) in drug development. Most of these reports pertain to
      the technological improvements that have allowed for drug concentration
      measurements from microliter volumes of sample, issues concerning method
      development, and exploration of the technique, into other areas such as
      measurement of macromolecules and metabolite identification. One area that has
      received less attention and is the subject of this commentary concerns the
      pharmacokinetic issues that arise from using DBS as opposed to plasma, the
      mainstay matrix. Measurements of drug concentrations from either plasma or dbs
      are almost always the sum of bound and unbound drug, but it is the unbound drug
      in plasma (plasma water) that is the relevant driver of essentially all
      pharmacokinetic and pharmacodynamic events. Therefore, the critical assumption
      made is constancy in fraction unbound for plasma, and additionally for blood,
      constancy of hematocrit and blood cell affinity. Often these assumptions are
      reasonable and either matrix suffices, but not always. Then the value of one
      matrix over the other depends on the magnitude of the blood-to-plasma
      concentration ratio of drug, its clearance and the cause of the deviation from
      constancy. Additional considerations are the kinetics of distribution within
      blood and those arising when the objective is assessment or comparison of
      bioavailability. Most of these issues can be explored and addressed in vitro
      prior to the main drug development program.

PMID- 21083485
TI  - Formation of a Global Contract Research Organization Council for Bioanalysis.

PMID- 21083486
TI  - Building the Global Bioanalysis Consortium - working towards a functional
      globally acceptable and harmonized guideline on bioanalytical method validation.

PMID- 21083488
TI  - Connecting strategies on dried blood spots.

PMID- 21083489
TI  - Effect of storage conditions on the weight and appearance of dried blood spot
      samples on various cellulose-based substrates.
AB  - BACKGROUND: Before shipping and storage, dried blood spot (DBS) samples must be
      dried in order to protect the integrity of the spots. In this article, we examine
      the time required to dry blood spot samples and the effects of different
      environmental conditions on their integrity. RESULTS: Under ambient laboratory
      conditions, DBS samples on Whatman 903((r)), FTA((r)) and FTA((r)) Elute
      substrates are dry within 90 min of spotting. An additional 5% of moisture is
      lost during subsequent storage with desiccant. When exposed to elevated
      conditions of temperature and relative humidity, the DBS samples absorb moisture.
      DBS samples on FTA lose this moisture on being returned to ambient conditions.
      DBS samples on 903 show no visible signs of deterioration when stored at elevated
      conditions. However, these conditions cause the DBS to diffuse through the FTA
      Elute substrate. CONCLUSION: Blood spots are dry within 90 min of spotting.
      However, the substrates examined behave differently when exposed to conditions of
      high relative humidity and temperature, in some cases resulting in the integrity
      of the substrate and DBS sample being compromised. It is recommended that these
      factors be investigated as part of method development and validation.

PMID- 21083490
TI  - Utility of dried blood spot sampling and storage for increased stability of
      photosensitive compounds.
AB  - BACKGROUND: Compound stability remains a major point of concern within
      pharmaceutical development. In attempts to minimize degradation, scientists may
      utilize acidification of samples prior to storage, dark chambers, decreased
      freezer temperatures and a variety of other stabilization techniques. All of
      these steps require additional procedures, increased costs and increased
      validation steps. Dried blood spots (DBS) are becoming a popular alternative to
      plasma sampling in many small- and even large-molecule applications. An
      investigation was performed in order to establish if DBS would provide storage
      advantages over liquid-based matrices for two light-sensitive compounds,
      nifedipine and omeprazole, to prevent or minimize photodegradation. RESULTS:
      Experimental data has shown, through forced and natural photodegradation
      experiments, that the compounds nifedipine and omeprazole exhibit increased
      photostability when spotted and stored on various DBS paper, when compared with
      water, plasma or whole blood. For omeprazole, between 40 and 90% loss was
      observed in liquid matrices, while photodegradation was negligible when utilizing
      DBS. Some loss of nifedipine is noted during exposure conditions on DBS; however,
      photodegradation in liquid matrices is far more severe. CONCLUSION: Within the
      experimental compound set, DBS technology offers a significant reduction in the
      photodegradation process when compared with the liquid matrices water, plasma or
      blood.

PMID- 21083491
TI  - Development and validation of an HPLC-MS/MS method for the analysis of
      dexamethasone from pig synovial fluid using dried matrix spotting.
AB  - BACKGROUND: Dried matrix spot techniques were employed to validate an HPLC-MS/MS
      assay for the determination of dexamethasone in clear Yorkshire pig synovial
      fluid using 15 ul of sample. We have adopted the term dried matrix spot to
      indicate that the techniques used for dried blood spots can be applied to
      nonblood matrices. The dried matrix spot method employs a color-indicating
      process developed at Alturas Analytics that enhances the ability to analyze
      transparent fluids spotted onto collection paper by allowing the analyst to
      visually verify the location of the dried sample spot. RESULTS: The method was
      shown to be accurate (+/-4.3%) and precise (14.2% at the LLOQ and <=10.0% at all
      other concentrations) across the dynamic range of the assay. CONCLUSION: The
      method shows the potential application of dried matrix spot techniques for the
      analysis of transparent biological fluids.

PMID- 21083492
TI  - Assay for screening for six antimalarial drugs and one metabolite using dried
      blood spot sampling, sequential extraction and ion-trap detection.
AB  - BACKGROUND: More parasites are becoming resistant to antimalarial drugs, and in
      many areas a change in first-line drug treatment is necessary. The aim of the
      developed assay is to help determine drug use in these areas and also to be a
      complement to interviewing patients, which will increase reliability of surveys.
      RESULTS: This assay detects quinine, mefloquine, sulfadoxine, pyrimethamine,
      lumefantrine, chloroquine and its metabolite desethylchloroquine in a 100-ul
      dried blood spot. Most of the drugs also have long half-lives that make them
      detectable at least 7 days after administration. The drugs are extracted from the
      dried blood spot with sequential extraction (due to the big differences in
      physicochemical properties), solid-phase extraction is used as sample clean-up
      and separation is performed with gradient-LC with MS ion-trap detection.
      CONCLUSION: Detection limits (S/N > 5:1) at 50 ng/ml or better were achieved for
      all drugs except lumefantrine (200 ng/ml), and thus can be used to determine
      patient compliance. A major advantage of using the ion-trap MS it that it will be
      possible to go back into the data and look for other drugs as needed.

PMID- 21083493
TI  - Validation of individual quantitative methods for determination of cytochrome
      P450 probe substrates in human dried blood spots with HPLC-MS/MS.
AB  - BACKGROUND: Robust individual reversed-phase HPLC-MS/MS methods have been
      validated for the quantitative bioanalysis of caffeine, flurbiprofen, midazolam,
      omeprazole and rosiglitazone in dried blood spot samples prepared from small
      volumes (15 ul) of human blood. Samples were punched and the resulting discs were
      extracted for analysis with methanol. Detection was by TurboIonSprayTM ionization
      combined with selected reaction monitoring MS. RESULTS: The validated analytical
      concentration ranges for caffeine, flurbiprofen, midazolam, omeprazole and
      rosiglitazone were 250 to 25,000 ng/ml, 100 to 10,000 ng/ml, 0.35 to 72 ng/ml, 5
      to 1000 ng/ml and 2.5 to 1000 ng/ml, respectively, and were appropriate to
      measure circulating concentrations for these analytes at therapeutic doses. The
      within-run precision and bias values for all methods were less than 15%. All
      compounds were stable in dried blood spots stored at room temperature and
      protected from moisture for at least 5 days and in whole blood for 2 h at 37
      degrees C. CONCLUSION: This work demonstrates that quantitative analysis of a
      drug extracted from dried blood spots can provide high-quality data while
      minimizing the volume of blood withdrawn from volunteers.

PMID- 21083494
TI  - Validation of a high-sensitivity assay for zatebradine in dried blood spots of
      human blood at pg/ml concentrations using HILIC-MS/MS.
AB  - BACKGROUND: One of the main reasons for the increased popularity of dried blood
      spots (DBS) is related to the 3Rs principles (replacement, refinement and
      reduction) for animal use in drug development. The small blood volume collected
      using this technique may have a significant impact on the assay sensitivity. An
      approach that made use of hydrophilic interaction chromatography (HILIC) to
      enhance the LC-MS assay sensitivity was explored and optimized for a tool
      compound. RESULTS: A very high-sensitivity assay in dried spots of human blood
      was validated in the range of 5 to 5000 pg/ml. The use of HILIC increased LC-MS
      sensitivity up to fivefold compared with other reversed phase chromatographic
      methods. CONCLUSION: The good compatibility of the DBS extracts with HILIC and
      the results of the assay validation for zatebradine at a very low LLOQ
      demonstrate the high potential and the high performance of this approach.

PMID- 21083495
TI  - Sensitive determination of a drug candidate in dried blood spots using a TLC-MS
      interface integrated into a column-switching LC-MS/MS system.
AB  - BACKGROUND: A thin-layer chromatography-mass spectrometry interface was
      previously reported to extract compounds from dried blood spots online. Here, we
      integrated this interface into a column-switching LC-MS/MS system for online
      solid-phase extraction and addressed internal standard addition. RESULTS: A drug
      was analyzed in dried blood spots with a lower limit of quantitation of 50 pg/ml.
      The internal standard was added via an autosampler to the extraction solvent. The
      method featured online aqueous dilution of the dried blood spots extract with
      subsequent trapping and gradient analytical separation. Good precision, accuracy
      and recovery were obtained. CONCLUSION: The thin-layer chromatography-mass
      spectrometry interface provided high reproducibility and good extraction
      efficiency. Although manually operated, it significantly reduced sample
      preparation efforts. The combination with online solid-phase extraction allowed
      enrichment of larger sample/extract volumes and efficient clean-up.

PMID- 21083496
TI  - A powerful couple in the future of clinical biochemistry: in situ analysis of
      dried blood spots by ambient mass spectrometry.
AB  - Since the early 1960s, dried blood spots (DBS) on filter paper have been used in
      clinical applications. The first key milestone in the use of DBS was the
      screening of phenylketonuria and other inborn errors of metabolism using
      microbiological and enzymatic analytical methods. 20 years after its
      introduction, advanced mass spectrometers and new soft ionization techniques have
      permitted the coupling of liquid chromatography with MS and tandem MS (MS/MS) and
      since the 1990s, DBS analysis by LC-MS/MS expanded screening to many inborn
      errors of metabolism simultaneously. Recently, DBS-LC-MS/MS analysis has been
      used in other fields such as pharmacology, toxicology and forensic sciences.
      Today, new ambient ionization techniques, coupled to MS, directly desorb/ionize
      molecules from solid samples. This presents new opportunities for the in situ
      analysis of DBS. Most likely, ambient MS methods will be used to analyze DBS,
      increasing the clinical applications of MS within the next 10 years.

PMID- 21083497
TI  - Dried blood spots in HIV monitoring: applications in resource-limited settings.
AB  - By the end of 2008, 4 million people were receiving antiretroviral treatment for
      HIV/AIDS in low- and middle-income countries. In industrialized countries,
      monitoring of treatment with viral load measurements and drug resistance testing
      is the standard of care to ensure early detection of treatment failure and a
      prompt switch to a fully active second-line regimen, before drug-resistant
      mutations accumulate. These tests, however, require highly specialized
      laboratories and stringent procedures for storage and shipment of plasma, and are
      rarely available in resource-limited settings. Therefore, treatment failure in
      such settings is usually not detected until patients develop severe
      immunodeficiency, at which stage widespread resistance is likely. Dried blood
      spots (DBS) are easy to collect and store, and can be a convenient alternative to
      plasma in settings with limited laboratory capacity. This review provides an
      overview of possible applications of DBS technologies in the monitoring of HIV
      treatment, with the main focus on viral load quantification and drug resistance
      testing.

PMID- 21083499
TI  - A prospective, single-blind, multicenter, dose escalation study of intracoronary
      iNOS lipoplex (CAR-MP583) gene therapy for the prevention of restenosis in
      patients with de novo or restenotic coronary artery lesion (REGENT I extension).
AB  - Neointimal hyperplasia causing recurrent stenosis is a limitation of the clinical
      utility of percutaneous transluminal coronary interventions (PCI). Nitric oxide
      (NO) inhibits smooth muscle cell proliferation, platelet activation, and
      inflammatory responses, all of which have been implicated in the pathogenesis of
      restenosis. In animals, neointimal proliferation after balloon injury has been
      shown to be effectively reduced by gene transfer of the inducible NO synthase
      (iNOS). The primary objective of this first multicenter, prospective, single
      blind, dose escalation study was to obtain safety and tolerability information of
      the iNOS lipoplex (CAR-MP583) gene therapy for reducing restenosis following PCI.
      Local coronary intramural CAR-MP583 delivery was achieved using the Infiltrator
      balloon catheter. A total of 30 patients were treated in the study (six patients,
      0.5 MUg; six patients, 2.0 MUg; six patients, 5.0 MUg; and 12 patients, 10 MUg).
      There were no complications related to local application of CAR-MP583. In one
      patient, PCI procedure-related transient vessel occlusion occurred with
      consecutive troponin elevation. There were no signs of inflammatory responses or
      hepatic or renal toxicity. No dose relationship was seen with regard to adverse
      events across the dose groups. Thus, coronary intramural lipoplex-enhanced iNOS
      gene therapy during PCI is feasible and appears to be safe. These initial
      clinical results are encouraging to support further clinical research, in
      particular in conjunction with new local drug delivery technologies.

PMID- 21083500
TI  - Identification and characterization of adenovirus early region 1B-associated
      protein 5 as a surface marker on undifferentiated human embryonic stem cells.
AB  - Pluripotent human embryonic stem cells (hESCs) provide appropriate systems for
      developmental studies and prospective donor cell sources for regenerative
      medicine. Identification of surface markers specific to hESCs is a prerequisite
      for studying hESC biology and can be used to generate clinical-level donor cell
      preparations that are free from tumorigenic undifferentiated hESCs. We previously
      reported the generation of monoclonal antibodies that specifically recognize hESC
      surface antigens using a decoy immunization strategy. In this study, we show that
      monoclonal antibody 57-C11 recognizes a phosphorylated form of adenovirus early
      region 1B-associated protein 5 (E1B-AP5). E1B-AP5 is a nuclear RNA-binding
      protein, but we report that 57-C11-reactive E1B-AP5 is expressed on the surface
      of undifferentiated hESCs. In undifferentiated hESCs, 57-C11-reactive E1B-AP5 is
      localized to SSEA3-, SSEA4-, TRA-1-60-, TRA-1-81-, OCT4-, SOX2-, and NANOG
      positive hESCs. In mixtures of undifferentiated hESCs and hESC-derived neurons,
      57-C11 exclusively recognizes undifferentiated hESCs but not hESC-derived
      neuronal cells. Further, the expression of 57-C11-reactive E1B-AP5 decreases upon
      differentiation. Our results demonstrate that 57-C11-reactive E1B-AP5 is a novel
      surface molecule that is involved in the undifferentiated state of hESCs. As far
      as we know, this is the first report demonstrating that heterogeneous nuclear RNA
      binding protein is expressed on the surface of undifferentiated hESCs.

PMID- 21083501
TI  - Disruption of hypoxia-inducible transcription factor-prolyl hydroxylase domain-1
      (PHD-1-/-) attenuates ex vivo myocardial ischemia/reperfusion injury through
      hypoxia-inducible factor-1alpha transcription factor and its target genes in
      mice.
AB  - Hypoxia-inducible transcription factor (HIF)-prolyl hydroxylases domain (PHD-1-3)
      are oxygen sensors that regulate the stability of the HIFs in an oxygen-dependent
      manner. Suppression of PHD enzymes leads to stabilization of HIFs and offers a
      potential treatment option for many ischemic disorders, such as peripheral artery
      occlusive disease, myocardial infarction, and stroke. Here, we show that
      homozygous disruption of PHD-1 (PHD-1(-/-)) could facilitate HIF-1alpha-mediated
      cardioprotection in ischemia/reperfused (I/R) myocardium. Wild-type (WT) and PHD
      1(-/-) mice were randomized into WT time-matched control (TMC), PHD-1(-/-) TMC
      (PHD1TMC), WT I/R, and PHD-1(-/-) I/R (PHD1IR). Isolated hearts from each group
      were subjected to 30 min of global ischemia followed by 2 h of reperfusion. TMC
      hearts were perfused for 2 h 30 min without ischemia. Decreased infarct size
      (35%+/-0.6% vs. 49%+/-0.4%) and apoptotic cardiomyocytes (106+/-13 vs. 233+/-21
      counts/100 high-power field) were observed in PHD1IR compared to wild-type
      ischemia/reperfusion (WTIR). Protein expression of HIF-1alpha was significantly
      increased in PHD1IR compared to WTIR. mRNA expression of beta-catenin (1.9-fold),
      endothelial nitric oxide synthase (1.9-fold), p65 (1.9-fold), and Bcl-2 (2.7
      fold) were upregulated in the PHD1IR compared with WTIR, which was studied by
      real-time quantitative polymerase chain reaction. Further, gel-shift analysis
      showed increased DNA binding activity of HIF-1alpha and nuclear factor-kappaB in
      PHD1IR compared to WTIR. In addition, nuclear translocation of beta-catenin was
      increased in PHD1IR compared with WTIR. These findings indicated that silencing
      of PHD-1 attenuates myocardial I/R injury probably by enhancing HIF-1alpha/beta
      catenin/endothelial nitric oxide synthase/nuclear factor-kappaB and Bcl-2
      signaling pathway.

PMID- 21083503
TI  - Effects of whole-body cryotherapy on a total antioxidative status and activities
      of antioxidative enzymes in blood of depressive multiple sclerosis patients.
AB  - OBJECTIVES: Oxidative stress (OS) plays an important role in the pathogenesis of
      multiple sclerosis (MS). In MS patients depression is often observed. Cryotherapy
      might have an effect on OS. The aim of this study was to compare the effects of
      whole body cryotherapy (WBCT) on changes in total antioxidative status (TAS) of
      plasma and activities of antioxidative enzymes in erythrocytes from depressive
      and non depressive MS patients. METHODS: Twenty-two MS patients with secondary
      progressive disease course (12 depressive and 10 non depressive) were treated
      with 10 exposures in a cryochamber. Before and after WBCT the plasma TAS and the
      activities of superoxide dismutase (SOD) and catalase (CAT) in the erythrocytes
      were measured. RESULTS: The level of TAS in depressive MS group was significantly
      lower than in non depressive MS (P < 0.0003). WBCT increased the level of TAS in
      depressive (P < 0.002) more than in non depressive MS patients (P < 0.01). WBCT
      treatment of MS patients resulted in the significant increase of TAS level in
      plasma but had no effects on activities of SOD and CAT. CONCLUSIONS: Our results
      indicate that WBCT suppresses OS in MS patients, especially in depressive
      patients.

PMID- 21083502
TI  - Dual roles of Oct4 in the maintenance of mouse P19 embryonal carcinoma cells: as
      negative regulator of Wnt/beta-catenin signaling and competence provider for
      Brachyury induction.
AB  - Transcription factor Oct4 is expressed in pluripotent cell lineages during mouse
      development, namely, in inner cell mass (ICM), primitive ectoderm, and primordial
      germ cells. Functional studies have revealed that Oct4 is essential for the
      maintenance of pluripotency in inner cell mass and for the survival of primordial
      germ cells. However, the function of Oct4 in the primitive ectoderm has not been
      fully explored. In this study, we investigated the role of Oct4 in mouse P19
      embryonal carcinoma (EC) cells, which exhibit molecular and developmental
      properties similar to the primitive ectoderm, as an in vitro model. Knockdown of
      Oct4 in P19 EC cells upregulated several early mesoderm-specific genes, such as
      Wnt3, Sp5, and Fgf8, by activating Wnt/beta-catenin signaling. Overexpression of
      Oct4 was sufficient to suppress Wnt/beta-catenin signaling through its action as
      a transcriptional activator. However, Brachyury, a key regulator of early
      mesoderm development and a known direct target of Wnt/beta-catenin signaling, was
      unable to be upregulated in the absence of Oct4, even with additional activation
      of Wnt/beta-catenin signaling. Microarray analysis revealed that Oct4 positively
      regulated the expression of Tdgf1, a critical component of Nodal signaling, which
      was required for the upregulation of Brachyury in response to Wnt/beta-catenin
      signaling in P19 EC cells. We propose a model that Oct4 maintains pluripotency of
      P19 EC cells through 2 counteracting actions: one is to suppress mesoderm
      inducing Wnt/beta-catenin signaling, and the other is to provide competence to
      Brachyury gene to respond to Wnt/beta-catenin signaling.

PMID- 21083505
TI  - Lower-limb prosthetic technologies in the developing world: A review of
      literature from 1994-2010.
AB  - In the mid-1990s, a number of key publications and meetings of experts identified
      major technical issues associated with prosthetic technologies intended for
      developing countries. These included inadequate durability of prosthetic feet,
      poor socket quality and prosthetic fit, improper alignment of prostheses, and
      inferior function of components. To examine the progress that has been made since
      then in addressing these issues, a comprehensive review of literature was
      performed. In total, 106 articles were selected and included in the review. The
      review examined prosthetic technologies categorized into feet and ankles, knees,
      sockets and suspension, and materials, structures, and alignment methods.
      Moreover, publications were categorized as technical development, clinical (lab
      based) testing, or clinical field testing studies. The results reveal important
      work that has been carried out to develop and implement standardized outcome
      measures during field testing, allowing various existing prosthetic technologies
      to be evaluated in terms of their use, function, durability, and other factors.
      Progress has also been made toward addressing the aforementioned limitations of
      prosthetic technologies, however, more research and development is required. This
      includes improving the durability of the external cosmetic features of prosthetic
      feet, developing more functional prosthetic knee joints, and simplifying
      fabrication techniques to further improve outcomes associated with socket fit and
      prosthetic alignment. Research and development collaborations between developed
      and developing countries, and the dissemination of ongoing research, development,
      and evaluation activities are essential to the advancement of prosthetic
      technologies in these regions.

PMID- 21083506
TI  - Comment on: An interim prosthesis program for lower limb amputees.

PMID- 21083507
TI  - Cellular models for the study of the pharmacology and signaling of melanin
      concentrating hormone receptors.
AB  - Cellular models for the study of the neuropeptide melanin-concentrating hormone
      (MCH) have become indispensable tools for pharmacological profiling and signaling
      analysis of MCH and its synthetic analogues. Although expression of MCH receptors
      is most abundant in the brain, MCH-R(1) is also found in different peripheral
      tissues. Therefore, not only cell lines derived from nervous tissue but also from
      peripheral tissues that naturally express MCH receptors have been used to study
      receptor signaling and regulation. For screening of novel compounds, however,
      heterologous expression of MCH-R(1) or MCH-R(2) genes in HEK293, Chinese hamster
      ovary, COS-7, or 3T3-L1 cells, or amplified MCH-R(1) expression/signaling in
      IRM23 cells transfected with the G(q) protein gene are the preferred tools
      because of more distinct pharmacological effects induced by MCH, which include
      inhibition of cAMP formation, stimulation of inositol triphosphate production,
      increase in intracellular free Ca(2+) and/or activation of mitogen-activated
      protein kinases. Most of the published data originate from this type of model
      system, whereas data based on studies with cell lines endogenously expressing MCH
      receptors are more limited. This review presents an update on the different
      cellular models currently used for the analysis of MCH receptor interaction and
      signaling.

PMID- 21083508
TI  - Exposure-response effects of inhaled sulfur mustard in a large porcine model: a 6
      h study.
AB  - CONTEXT: Inhalation of sulfur mustard (HD) vapor can cause life-threatening lung
      injury for which there is no specific treatment. A reproducible, characterized in
      vivo model is required to investigate novel therapies targeting HD-induced lung
      injury. MATERIALS AND METHODS: Anesthetized, spontaneously breathing large white
      pigs (~50 kg) were exposed directly to the lung to HD vapor at 60, 100, or 150
      ug/kg, or to air, for ~10 min, and monitored for 6 h. Cardiovascular and
      respiratory parameters were recorded. Blood and bronchoalveolar lavage fluid
      (BALF) were collected to allow blood gas analysis, hematology, and to assay for
      lung inflammatory cells and mediators. Urine was collected and analyzed for HD
      metabolites. Histopathology samples were taken postmortem (PM). RESULTS: Air
      exposed animals maintained normal lung physiology whilst lying supine and
      spontaneously breathing. There was a statistically significant increase in shunt
      fraction across all three HD-exposed groups when compared with air controls at 3
      6 h post-exposure. Animals were increasingly hypoxemic with respiratory acidosis.
      The monosulfoxide beta-lyase metabolite of HD (1-methylsulfinyl-2
      [2(methylthio)ethylsulfonyl)ethane], MSMTESE), was detected in urine from 2 h
      post-exposure. Pathological examination revealed necrosis and erosion of the
      tracheal epithelium in medium and high HD-exposed groups. CONCLUSION: These
      findings are consistent with those seen in the early stages of acute lung injury
      (ALI).

PMID- 21083509
TI  - Application of human pancreatic carcinoid BON cells for receptor-targeted drug
      development.
AB  - In our previous study, we found that several tumor cell lines displayed high
      receptor-specific binding affinity, one of which, the human pancreatic carcinoid
      BON cell line, demonstrates high affinity binding of the bombesin (BN) and
      somatostatin (SST) receptor-specific ligands. In the present study, BON cells, as
      a representative model, were further applied to evaluate various peptide analogs
      and cytotoxic receptor-targeted peptide conjugates. We observed quick ligand
      receptor internalization in BON cells as well as high binding affinity.
      Furthermore, BON cells have high expression of multidrug resistance-associated
      genes (MDR1) and show camptothecin (CPT) resistance. Various receptor-specific
      cytotoxic conjugates were synthesized and evaluated in the BON cell model via in
      vitro and in vivo studies. We found that all the tested conjugates displayed
      potent antitumor ability in xenografts. Especially, the CPT conjugates, CPT-SST,
      and CPT-BN, are most likely to increase sensitivity to CPT-resistant BON cells.
      Our findings suggest that appropriately defined tumor cell lines may provide
      physiologically relevant cell-based evaluations of novel peptide analogs and
      receptor-targeted chemotherapeutics.

PMID- 21083511
TI  - Primary cutaneous anaplastic CD30 + large-cell lymphoma that completely regressed
      after incisional skin biopsy.
AB  - We describe a 48-year-old woman with three erythematous nodules localized on the
      left forearm, with 2 months evolution. Histological and immunohistochemical
      examination revealed a CD30(+) large-cell lymphoma. Systemic involvement was not
      detected. The tumor regressed spontaneously within a week, after the incisional
      skin biopsy. In control skin biopsy, there was not any histological feature of
      lymphoma. No reactivation or any symptom of systemic disease was observed during
      the 10-month follow-up period.

PMID- 21083510
TI  - Part 2. Comparison of emergency washing solutions in 70% hydrofluoric acid-burned
      human skin in an established ex vivo explants model.
AB  - BACKGROUND: Hydrofluoric acid (HF) is a small and partially dissociated acid
      (pK(a) 3.2), able to deeply penetrate into human skin in addition to the
      corrosiveness of the hydrogen ion (H(+)) and the toxicity of the fluoride ion (F(
      )). However, there has been a lack of experimental studies to objectively
      characterize the results of human HF skin exposure decontamination.
      METHODOLOGY/PRINCIPAL FINDINGS: A previously established experimental method
      using a human skin explants ex vivo model (Part 1. Experimental 70% hydrofluoric
      acid (HF) burns: Histological observations in an established human skin explants
      ex vivo model) described the lesions that appeared following 70% HF penetration.
      Within 5 min, 70% HF penetrates to the dermis. Using the same experimental
      conditions, a comparison study of two different washing protocols was performed:
      water + topical calcium gluconate (CaG) versus Hexafluorine((r)). In these
      conditions, washing for 15 min with running tap water followed by topical CaG
      ointment only delayed burn onset, while severe tissue damage appeared later. In
      contrast, after washing with Hexafluorine((r)) over 10 min, no histological
      lesions developed. These results are in accordance with the results of accidental
      human industrial case reports. CONCLUSION/SIGNIFICANCE: Amphoteric and hypertonic
      Hexafluorine((r)) can deactivate H(+) and chelate F(-) ions. Based on these
      results, it should be considered as a promising first-aid decontamination
      solution to prevent or minimize significant local and systemic consequences of
      concentrated HF skin exposures.

PMID- 21083512
TI  - Economic costs of Shiga toxin-producing Escherichia coli infection in Australia.
AB  - Shiga toxin-producing Escherichia coli (STEC) infections are an important cause
      of foodborne disease in Australia. Three percent to 7% of sporadic patients
      develop hemolytic uremic syndrome (HUS) and 40% of patients with HUS develop
      chronic complications. To examine costs associated with illness, we interviewed
      patients notified to the South Australian Department of Health with a structured
      questionnaire regarding severity of illness, medical treatment, time lost from
      work, hospitalization, and other costs. In 2003-2006, we interviewed 46 patients
      of STEC infection, 2 of whom developed HUS. The median duration of illness was 7
      days (range 3-31 days) and 41% (19/46) of patients were admitted to hospital. The
      estimated total cost for the 46 STEC cases in South Australia was AUD$144,087,
      equating to a mean cost of AUD$3132 per case. We estimate that the annual total
      costs of STEC infection in South Australia and Australia are AUD$200,283 and
      AUD$2,633,181, respectively. We used linear regression to identify that STEC
      infection costs increase by AUD$608 per day regardless of severity, and that more
      severe illness is strong predictor of cost. This is the first Australian study to
      examine costs of STEC infection and highlights the significant impact of this
      illness.

PMID- 21083513
TI  - Pharmacotherapy of low back pain: targeting nociceptive and neuropathic pain
      components.
AB  - AIM: To review pharmacological management of chronic low back pain (LBP), with
      respect to management of nociceptive and neuropathic components. METHODS: Studies
      were identified by a PubMed search of English-language papers from the last 10 
      years, with additional hand searches of relevant reviews. DISCUSSION:
      Paracetamol, non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2
      inhibitors target the nociceptive component of chronic LBP, and do not affect
      neuropathic pain mechanisms. Antidepressants target the neuropathic component of
      chronic LBP; however, conflicting efficacy results have been reported. Opioids
      target both nociceptive and to a lesser extent neuropathic pain. They are
      effective in chronic LBP, but many patients require higher doses or combination
      treatment. The long-term efficacy of opioids in chronic LBP has been questioned
      because of the absence of high-quality data and concerns regarding tolerability
      and dependence. The topical preparation lidocaine 5% plaster, indicated in post
      herpetic neuralgia, is effective in localized neuropathic pain in patients with
      chronic LBP. Pregabalin is ineffective as monotherapy for chronic LBP but is
      effective when combined with celecoxib or opioids. Muscle relaxant monotherapy is
      ineffective in chronic LBP. Combination therapy is often necessary in patients
      with chronic LBP, in order to manage both nociceptive and neuropathic pain
      components. CONCLUSION: Chronic LBP often comprises both nociceptive and
      neuropathic components, therefore a multimodal and individualized treatment
      approach is necessary. Combining drugs with different mechanisms of action (e.g.
      an agent with u-receptor activity plus an agent of a different class) represents
      a rational approach to management of chronic LBP with both nociceptive and
      neuropathic components.

PMID- 21083514
TI  - Zoledronic acid therapy impacts risk and frequency of skeletal complications and
      follow-up duration in prostate cancer patients with bone metastasis.
AB  - PURPOSE: To evaluate the effects of timing and length of zoledronic acid (ZA)
      treatment on outcomes for patients with prostate cancer in clinical practice.
      MATERIALS AND METHODS: Patients with prostate cancer and first bone metastasis
      diagnosed from January 2003 to October 2006 were included. Patients were
      considered 'untreated' if no ZA was given, 'early ZA-treated' if ZA was initiated
      before skeletal complication (SC) occurrence or 'late ZA-treated' if one or more
      SC was documented before or at ZA initiation. Patients were classified with short
      (<= 90 days), medium (91-180 days) or long (>180 days) treatment persistence.
      Assessments included follow-up duration (FUP) and risk of developing one or more
      SC. RESULTS: Among eligible patients, 847 were untreated, 243 were early ZA
      treated and 218 were late ZA-treated. For untreated versus early ZA-treated
      groups, median FUP was 263 versus 357 days (p < 0.0001), respectively, and time
      to first SC was 199 versus 273 days (p < 0.0001), respectively. ZA treatment was
      associated with significantly longer FUP and lower SC risk. The early ZA-treated
      group had significantly longer FUP versus the late ZA-treated group (median days,
      357 vs. 299.5); the late ZA-treated group experienced significantly higher SC
      risk vs. the early ZA-treated group (odds ratio, 1.51). Compared with the long
      persistence group, FUP was 56% and 40% shorter in the short and medium groups,
      respectively (p < 0.0001). CONCLUSION: Treatment with and early initiation of ZA
      for patients with prostate cancer and bone metastasis significantly prolonged
      time to and reduced risk of developing SC, while extending FUP.

PMID- 21083515
TI  - Observational, nonintervention, multicenter study for validation of the Bowel
      Function Index for constipation in European countries.
AB  - OBJECTIVE: Constipation is a common adverse event of treatment with opioids for
      chronic non-malignant pain and may result in a considerable reduction in health
      related quality of life. The aim of this study was to assess the psychometric
      properties of the Bowel Function Index (BFI) in european patients suffering from
      constipation secondary to opioid analgesic treatment for chronic, non-malignant
      pain. METHODS: This was a multinational study conducted at 15 clinical sites in
      the Czech Republic, Germany, Italy, and the United Kingdom. Patients suffering
      from constipation secondary to opioid analgesic treatment for chronic, non
      malignant pain were recruited to complete a series of questionnaires including a
      socio-demographic form, the BFI, the Patient Assessment of Constipation -
      Symptoms (PAC-SYM), a global frequency item, and a clinical form. RESULTS: A
      total of 131 patients were included in this study. Inter-item correlations of the
      BFI were statistically significant in the moderate to large range and the
      analysis indicated a strong degree of internal consistency (Cronbach's alpha =
      0.86). All correlations between the BFI and the global item were statistically
      significant in the moderate to high range (r = 0.59 to 0.69; p < 0.0001).
      Correlations between the BFI and the PAC-SYM were moderate and statistically
      significant (p < 0.01 to 0.0001). CONCLUSIONS: Although this study was limited by
      the relatively small sample size, it is a part of an extensive validation
      program. This study suggests that the BFI is a reliable and valid measure of
      constipation-related symptomatology in chronic pain patients. This measure may be
      a valuable indicator of patients' experience of symptoms of opioid treatment of
      chronic pain in future trials.

PMID- 21083516
TI  - Effects of enoxaparin preparations on thrombin generation and their correlation
      with their anti-FXa activity.
AB  - OBJECTIVE: Anticoagulant effect of LMWHs is monitored by anti-factor Xa (anti
      FXa) activity assay. Since this test has several limitations, the aim of this
      study was to explore the activity of two LMWHs by thrombin generation assay (TG,
      which presents an overall picture of hemostatic balance) and its correlation with
      their anti-FXa activity. METHODS: In an open-label, randomized cross-over study,
      40  mg of two enoxaparins, the original branded formulation (R) and another one,
      also marketed in Argentina (T), were daily injected subcutaneously, for 7 days,
      to 20 healthy volunteers, with a 7-day washout interval. Blood samples were
      collected before treatment and 180  minutes after the injection on days 3 and 7.
      TG in platelet-poor plasma activated with tissue factor was assessed by lag time
      (LT), time to peak (TTP), peak (PTG), and endogenous thrombin potential (ETP).
      Anti-FXa and anti-FIIa activities, free tissue factor pathway inhibitor (free
      TFPI), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type
      1 (PAI-1), and euglobulin lysis time (ELT) were also assayed. RESULTS: The mean
      (SD) anti-FXa (UI/ml) for T and R increased on days 3 and 7. LT and TTP were
      significantly prolonged by both LMWHs, with no differences between them. The mean
      ETP (nmol/L) for T and R at 3 and 7 days after treatment were significantly
      reduced when compared with basal values (p = 0.001 for all). On day 3, a
      significant correlation was shown between the variables describing TG and anti
      FXa for T and R, without differences between them, for LT (r: 0.516 and 0486),
      ETP (r: 0.532 and 0.574), PEAK (r: 0.482 and 0.501), and TTP (r: 0.577 and
      0.503), respectively. This correlation was also significant on day 7. Anti-FIIa
      activity and free TFPI increased significantly at 3 and 7 days for both LMWHs,
      without differences between them. R and T decreased ELT and PAI-1, but had no
      effect on t-PA. There were no differences between both LMWHs in routine
      hemostatic tests. No adverse events were reported. CONCLUSIONS: Correlation
      between TG and anti-FXa activity was good. Both enoxaparins induced similar
      change of coagulation parameters, with a significant increase in fibrinolytic
      activity.

PMID- 21083517
TI  - Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma
      patients.
AB  - BACKGROUND: Several studies have demonstrated the beneficial effects of
      omalizumab in asthma patients. Here we describe the drug's tolerance and oral
      corticosteroid sparing capacity in a long-term observational study. METHODS:
      Thirty-two patients aged >=18 years with obstructive airway disease and FEV(1)
      reversibility >=12% and 200  mL, with an oral steroid requirement >=7.5  mg per
      day of prednisolone during a period of >=1 year, a positive prick test or in
      vitro reactivity (RAST) to at least one perennial aeroallergen and a baseline
      immunoglobulin E level ranking between 30-700  IU/mL were prospectively followed
      for 17.2  +/-  8.5 months. Patients were visited once or twice a month, depending
      on their schedule for omalizumab administration. INTERVENTION: blood analysis
      every six months; spirometry and nitric oxide measurement at every visit.
      RESULTS: One patient who dropped out early was excluded. Follow-up period: the
      treatment benefited 83.9% (26/31) of the cohort; oral corticosteroids were
      reduced from 7.19 +/- 11.1 to 3.29 +/- 11.03  mg (p < 0.002) and withdrawn in
      74.2% of patients. FEV(1) (percent predicted) was 64.4 +/- 22.7 at the beginning
      and 62.9 +/- 24.3 at the end. IgE at entry was 322.2 +/- 334.2  IU/mL and
      increased 2.34-fold. Respiratory function and NO did not present statistically
      significant changes. We identified three groups of patients: the first (n = 17)
      receiving oral steroid at entry in whom the accumulated dose of oral steroids
      progressively decreased; another (n = 10) including patients who had quit oral
      steroids before starting omalizumab although they had not been instructed to do
      so and whose oral steroid dose at the end of follow-up was zero; and a third
      group (n = 4) that did not benefit from omalizumab treatment. The only relevant
      side effect was a flu-like syndrome which required discontinuation of treatment
      in one patient. CONCLUSION: In our series, a substantial, safe decrease in oral
      corticosteroid requirements was observed due, at least to some extent, to
      omalizumab therapy. Oral corticosteroids were withdrawn in three-quarters of the
      patients. We were unable to identify a factor able to predict which patients
      would benefit most from omalizumab treatment.

PMID- 21083518
TI  - Prevalence of antimicrobial resistance among Salmonella isolates from chicken in
      China.
AB  - We evaluated the antimicrobial resistance of Salmonella isolated in 2008 from a
      chicken hatchery, chicken farms, and chicken slaughterhouses in China. A total of
      311 Salmonella isolates were collected from the three sources, and two serogroups
      of Salmonella were detected, of which 133 (42.8%) consisted of Salmonella indiana
      and 178 (57.2%) of Salmonella enteritidis. The lowest percentage of S. indiana
      isolates was found in the chicken hatchery (4.2%), followed by the chicken farms
      (54.9%) and the slaughterhouses (71.4%). More than 80% of the S. indiana isolates
      were highly resistant to ampicillin (97.7%), amoxicillin/clavulanic acid (87.9%),
      cephalothin (87.9%), ceftiofur (85.7%), chloramphenicol (84.9%), florfenicol
      (90.9%), tetracycline (97.7%), doxycycline (98.5%), kanamycin (90.2%), and
      gentamicin (92.5%). About 60% of the S. indiana isolates were resistant to
      enrofloxacin (65.4%), norfloxacin (78.9%), and ciprofloxacin (59.4%). Of the S.
      indiana isolates, 4.5% were susceptible to amikacin and 5.3% to colistin. Of the
      S. enteritidis isolates, 73% were resistant to ampicillin, 33.1% to
      amoxicillin/clavulanic acid, 66.3% to tetracycline, and 65.3% to doxycycline,
      whereas all of these isolates were susceptible to the other drugs used in the
      study. The S. indiana isolates showed resistance to 16 antimicrobial agents.
      Strains of Salmonella (n = 108) carrying the resistance genes floR, aac(6')-Ib
      cr, and bla(TEM) were most prevalent among the 133 isolates of S. indiana, at a
      frequency of 81.2%. The use of pulsed-field gel electrophoresis to analyze the S.
      indiana isolates that showed similar antimicrobial resistance patterns and
      carried resistance genes revealed six genotypes of these organisms. Most of these
      isolates had the common pulsed-field gel electrophoresis patterns found in the
      chicken hatchery, chicken farms, and slaughterhouses, suggesting that many
      multidrug-resistant isolates of S. indiana prevailed in the three sources. Some
      of these isolates were not derived from a specific clone, but represented a
      variety of genotypes of S. indiana.

PMID- 21083519
TI  - Diabetes area participation analysis: a review of companies and targets described
      in the 2008 - 2010 patent literature.
AB  - IMPORTANCE OF THE FIELD: Type 2 diabetes is a chronic disease characterized by
      the development of insulin resistance, impaired pancreatic beta-cell function
      and, ultimately, hyperglycemia. The disease is highly associated with obesity and
      it is thought that the inappropriate deposition of lipid in tissues such as liver
      and muscle contributes to a reduction in insulin sensitivity which, in turn,
      places a burden on the beta-cell to secrete more insulin to achieve
      normoglycemia. Over an extended period of time, this can result in beta-cell
      failure and diminished glycemic control. When poorly managed, type 2 diabetes
      increases the risk of developing both microvascular and macrovascular
      complications, including retinopathy, nephropathy and coronary artery disease.
      The number of Americans with diabetes has approached 24 million in 2007 and the
      prevalence of the disease is projected to increase with the sedentary lifestyles
      and high caloric diets that are common today. First-line treatment for the
      disease involves lifestyle modifications and, if unsuccessful, pharmacotherapy to
      control symptoms. Anti-diabetic drugs belonging to several mechanistic classes
      are available (e.g., insulin secretagogues, insulin sensitizers, insulin mimetics
      and DPP IV inhibitors); however, many of these drugs lose their effectiveness
      over time, are not well-tolerated in some patients or may have suboptimal
      risk:benefit ratios. The search for new anti-diabetic drugs has continued to
      attract considerable interest from both academia and the pharmaceutical industry.
      AREAS COVERED IN THIS REVIEW: An analysis of 2008 - 2010 patent applications
      claiming diabetes as an indication has been undertaken. WHAT THE READER WILL
      GAIN: An understanding of: i) the pharmaceutical companies that have filed patent
      applications in the anti-diabetes area during 2008 - 2010; ii) the different
      pharmacological targets under investigation and the patent activity around such
      targets; iii) some of the targets in the research portfolios of selected
      companies; iv) chemical structures of compounds that modulate emerging targets
      and v) the pharmacological rationale underlying several targets with the largest
      patent counts. TAKE HOME MESSAGE: Type 2 diabetes is a complex disease with many
      potential points of intervention for pharmacotherapy. A majority of anti-diabetic
      patent applications claim chemical matter for just eight targets which include
      five enzymes, a GPCR, a family of nuclear hormone receptors and a class of sodium
      dependent glucose co-transporters (11beta-HSD1, DGAT1, DPP IV, glucokinase,
      GPR119, PPAR-alpha, -delta, -gamma, SGLT1 and SGLT2, and stearoyl-CoA desaturase
      1 (SCD1)). The major pharmaceutical companies are all pursuing some combination
      of these top eight targets. Several companies stand out for the breadth of new
      targets under investigation (e.g., F. Hoffmann-La Roche, Merck & Co., Pfizer,
      Takeda Pharmaceuticals, Sanofi-Aventis).

PMID- 21083520
TI  - Targeting survivin in cancer: patent review.
AB  - IMPORTANCE OF THE FIELD: Survivin is a prominent anti-apoptotic molecule
      expressed widely in the majority of cancers. Overexpression of survivin leads to
      uncontrolled cancer cell growth and drug resistance. Efficient downregulation of
      survivin expression and its functions can sensitise the tumour cells to various
      therapeutic interventions such as chemotherapeutic agents leading to cell
      apoptosis. AREAS COVERED IN THIS REVIEW: The article thoroughly analyses up-to
      date information on the knowledge generated from the survivin patents. Various
      key areas of research in terms of understanding survivin biology and its
      targeting are discussed in detail. WHAT THE READER WILL GAIN: The article clearly
      gives an insight on the recent developments undertaken to understand the roles of
      survivin in cancer and in validating various treatment paradigms that suppress
      survivin expression in cancer cells. TAKE HOME MESSAGE: Most recent developments
      are helpful for effectively downregulating survivin expression by using various
      therapeutic platforms such as chemotherapeutic drugs, immunotechnology,
      antisense, dominant negative survivin mutant, RNA interference and peptide-based
      methods. However, selective and specific targeting of survivin in cancer cells
      still poses a major challenge. Nanotechnology-based platforms are currently under
      development to enable site-specific targeting of survivin in tumour cells.

PMID- 21083522
TI  - Farnesyltransferase inhibitors: where are we now?
AB  - IMPORTANCE OF THE FIELD: Farnesyltransferase inhibitors (FTIs) target multiple
      pathways implicated in the pathogenesis of solid and hematologic malignancies.
      AREAS COVERED IN THIS REVIEW: Novel preclinical and clinical data on FTIs. WHAT
      THE READER WILL GAIN: Results of clinical trials of FTIs are critically
      summarized: Phase I - II studies demonstrated that tipifarnib (the most
      extensively investigated FTI) had antileukemic activity. The rates of complete
      response (CR), partial response (PR) and/or CR with incomplete platelet recovery
      (CRp) in patients with MDS and refractory/poor-risk AML were 5 - 25% and 11 -
      14%, respectively (hematological improvement, 17 - 35% and 8 - 9.5%,
      respectively). A Phase III study comparing tipifarnib with best supportive care,
      including hydroxyurea in patients with untreated AML >= 70 years old showed no
      survival benefit in the tipifarnib arm. A two-gene classifier (RASGRP1:APTX gene
      expression ratio) predicted response and survival, indicating that a two-gene
      expression assay may help select patients with AML who would benefit from
      tipifarnib. TAKE HOME MESSAGE: Patient selection should become a priority for
      targeted agent drug development. Clinical trials selecting patients who would
      benefit from FTIs should be designed to define the role of FTIs in the treatment
      of hematological malignancies and solid tumors.

PMID- 21083523
TI  - Modulation of intracellular signaling using protein-transduction technology.
AB  - Protein-transduction technology is one of the most promising therapeutic tools
      for the control of intracellular events. A number of studies have demonstrated
      that minimal and efficient protein-transduction domains (PTDs) can act as a
      peptide vector to transfer bioactive cargo molecules from outside to inside the
      cell. PTD-mediated transduction has the ability to cross the blood-brain barrier,
      with transduction taking place in most tissues and cell types in vivo. Thus,
      recombinant proteins fused to or conjugated with PTDs have the potential to be
      harnessed as supplementary and/or intervention agents directly modulating cell
      signaling and/or metabolism, or to be applied to vaccine antigens/adjuvants that
      are efficiently delivered to the optimal site of action to enhance vaccine
      immunogenicity. This review introduces the mechanism of action, recent
      applications, and future perspectives of protein-transduction technology as an
      alternative therapeutic in the post-genome era.

PMID- 21083524
TI  - Insights into monocyte-driven osteoclastogenesis and its link with hematopoiesis:
      regulatory roles of PECAM-1 (CD31) and SHP-1.
AB  - Osteoclasts are derived from hematopoietic cells of monocyte-macrophage lineage.
      Osteoclastogenesis is orchestrated by the migration of monocytic osteoclast
      progenitor cells in close proximity to bone surfaces destined for resorption.
      Although the overall roles of monocyte migratory behavior in osteoclastogenesis
      remain enigmatic, impaired monocyte migration can lead to either decreased or
      increased osteoclastogenesis, which appears contingent upon the roles of
      migration in either fusion events required for osteoclast formation or terminal
      differentiation of osteoclasts. The cell adhesion molecule PECAM-1 (platelet
      endothelial cell adhesion molecule 1), in concert with the tyrosine phosphatase
      SHP-1 (Src homology 2-containing protein tyrosine phosphatase 1) and tyrosine
      kinase Syk-1 (spleen tyrosine kinase 1), functions as a negative regulator of
      osteoclastogenesis. Both PECAM-1 (CD31) and SHP-1 knockout mice exhibit not only
      increased osteoclastogenesis but also abnormal hematopoiesis, which is suggestive
      of the intricate interplay between hematopoiesis and osteoclastogenesis.
      Interestingly, the most pronounced effect of PECAM-1 deficiency on hematopoiesis
      is reflected by excessive megakaryocytopoiesis. Emerging data have suggested the
      role of megakaryocytes in bone remodeling. Megakaryocytopoiesis
      osteoclastogenesis interactions are discussed herein, reconciling the
      discrepancies shown by different studies in this area. PECAM-1 and non-receptor
      tyrosine phosphatase polymorphisms have been revealed in a spectrum of diseases.
      The complex regulatory roles of PECAM-1 and SHP-1 in vivo suggest the potential
      utilization of polymorphisms of these genes for diagnostic purposes.

PMID- 21083525
TI  - Regulatory T-cell trafficking: from thymic development to tumor-induced immune
      suppression.
AB  - Regulatory T cells (Tregs) have become a priority for many investigators in
      immunology due to their potent immunosuppressive and tolerogenic effects. While
      Treg activity is required for normal immune homeostasis, dysregulation of their
      numbers can induce autoimmunity or aid in the pathogenesis of disease. Therefore,
      great effort has been made to understand the mechanisms by which Tregs accumulate
      in different areas of the body. Like other lymphocytes, Tregs migrate in response
      to a network of chemotactic stimuli involving chemokines, chemokine receptors,
      integrins, and their corresponding ligands. However, many of these stimuli are
      exclusive to Tregs, inducing their migration while leaving conventional
      populations unaffected. It is these selective stimuli that result in increased
      ratios of Tregs among conventional effector populations, leading to changes in
      immune suppression and homeostasis. This review explores selective Treg
      trafficking during thymic Treg development, migration to secondary lymphoid
      tissues and emigration into the periphery during homeostatic conditions,
      inflammation, and the tumor microenvironment, placing emphasis on stimuli that
      selectively recruits Tregs to target locations.

PMID- 21083526
TI  - A CCL2-based fusokine as a novel biopharmaceutical for the treatment of CCR2
      driven autoimmune diseases.
AB  - Autoimmune diseases represent one of the most challenging clinical entities with
      unmet medical needs, so the continued development of novel therapeutics is well
      justified. Most autoimmune diseases are marked by the infiltration of
      lymphomyeloid cells in target tissues, leading to inflammation and tissue damage.
      This process is guided by chemokines that act as signaling bridges amidst a
      complex network of immune cells. For example, monocytes are believed to be the
      primary cell type responsible for pathology initiation and tissue damage, while T
      lymphocytes are thought to orchestrate the process by secreting more
      cytokines/chemokines to amplify leukocyte homing. Many studies have addressed the
      molecular basis of monocyte recruitment in different autoimmune diseases, and the
      conclusions pointed to a major role played by monocyte chemoattractant protein 1
      (MCP-1), also known as CC chemokine ligand 2 (CCL2), and its cell-surface
      receptor, CC chemokine receptor (CCR) 2. These findings suggest that by
      interfering with CCL2 or its receptor, it is possible to inhibit the progression
      of CCR2-dependent diseases. Therefore, future therapy design targeting a
      maladapted immune response could target chemokine receptors starting with the
      CCL2-CCR2 axis.

PMID- 21083528
TI  - Cancer chemotherapy with lipid-based nanocarriers.
AB  - Nanotechnology has a profound effect on many areas of scientific research. Having
      grown exponentially, the focus of nanotechnology has been on therapeutic
      activity, such as cancer treatment. Lipid-based nanocarriers have attracted
      increasing scientific and commercial attention in the last few years as
      alternative carriers for the delivery of anticancer drugs. Lipid-based
      nanocarriers have played significant roles in the formulation of anticancer drugs
      to improve therapeutics. Shortcomings frequently encountered with anticancer
      compounds, such as poor solubility, normal tissue toxicity, poor specificity and
      stability, as well as the high incidence rate of drug resistance, are expected to
      be overcome through use of lipid-based nanocarriers. In this review, the
      advantages and methods of using nanocarriers to improve cancer treatment
      efficiency will be discussed. In addition, types of lipid-based nanocarriers are
      presented and hotspots in research are highlighted. It is anticipated that, in
      the near future, lipid-based nanocarriers will be further improved to deliver
      cytotoxic anticancer compounds in a more efficient, specific and safe manner.

PMID- 21083529
TI  - Polymeric and lipid-based materials for topical nanoparticle delivery systems.
AB  - The delivery of drugs and cosmetic actives to the skin by nanoparticle
      formulations has a number of advantages over conventional formulations.
      Nanoparticle formulations offer protection of incorporated active compounds
      against chemical degradation, more flexibility in modulating the release of the
      compound, the use of well-tolerated excipients, and feasibility of large scale
      production. The materials used in the nanoparticle synthesis and formulation can
      influence product stability, active ingredient properties and delivery to the
      intended site of action. This review describes the characteristics and
      application of various polymeric and lipid materials in the preparation of
      nanoparticles for topical and transdermal drug delivery.

PMID- 21083530
TI  - Perioperative quality-of-care measures for patients undergoing total hip or total
      knee replacement.
AB  - Recent years have seen the proliferation of numerous standards of quality for the
      process of providing health care, including total joint replacement. These
      attempts include the implementation of pay-for-reporting and pay-for-performance
      programs based on quality measures. These programs have often been implemented
      with few studies of the validity of the quality measures used and with limited
      input from the orthopedic community. Our project addresses this relative lack of
      evidence-based measures by developing a set of quality measures that address the
      perioperative care of patients undergoing total joint replacement. Our goal is to
      create a model for improving the quality of care and outcomes of total joint
      replacement in the United States by facilitating physicians in their efforts to
      apply the best scientific evidence to their daily practice.

PMID- 21083531
TI  - 10-year evaluation of the cementless low-contact- stress rotating-platform total
      knee arthroplasty.
AB  - We present the clinical and radiographic outcomes of the cementless low-contact
      stress (LCS) rotating-platform total knee arthroplasty. Overall, 423 prostheses
      were implanted in 393 consecutive patients (30 patients had bilateral total knee
      replacement) for primary varus gonarthrosis (381 patients) and rheumatoid
      arthritis (12 patients). There were 81 men and 312 women with a mean age of 73
      years (range, 58-85 years). Patella replacement was not performed in any case.
      Clinical and radiographic evaluation was performed using the Knee Society Score
      (KSS) and the Knee Society Assessment Form, respectively. The mean follow-up was
      10 years (range, 5-15 years). Three patients were lost to follow-up. Survival of
      the prostheses was 98% at 10 years; three prostheses required revision for deep
      infection, bearing dislocation, and periprosthetic fracture. The mean KSS
      improved significantly, from 42 and 44 points preoperatively to 90 and 79 points,
      respectively, at the latest evaluation (P < 0.001); results were excellent in 278
      cases, good in 106, fair in 27, and poor in nine. Radiolucent lines were observed
      in 80 cases; revision arthroplasty was not performed in any of these cases.
      Complications included deep infection in one patient, bearing dislocation in one,
      skin necrosis in four, and a supracondylar fracture in one. The cementless LCS
      rotating-platform total knee arthroplasty is associated with excellent mid- and
      long-term results for patients with osteoarthritis and rheumatoid arthritis of
      the knee.

PMID- 21083532
TI  - Biomechanical evaluation of degree of freedom of movements of a novel high
      flexion knee for its suitability in eastern lifestyles.
AB  - The total knee arthroplasty is the end-stage surgical procedure for pain relief
      in degenerative diseases such as arthritis. There have been many models designed
      in the five to six decades of arthroplasty history. This research has helped us
      in designing a new artificial high-flexion knee, which emphasizes a high flexion
      extension range of over 125 degrees. This range provides comfort while squatting,
      even after the total knee replacement. This article discusses the usage of this
      novel design in the day-to-day activities of people in the Eastern world. The
      standard flexion-extension level of a normal knee was taken into account and
      verified on the new design. The results have been satisfactory, and the models
      have been proven to provide comfort during partial squatting. Our results show
      that this novel high-flexion knee provides three degrees of freedom compared with
      the six degrees of freedom in a natural knee.

PMID- 21083527
TI  - Inflammasomes and their activation.
AB  - The innate immune system relies on the recognition of pathogens by pattern
      recognition receptors as a first line of defense and to initiate the adaptive
      immune response. Substantial progress has been made in defining the role of Nod
      (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in
      melanoma 2) as pattern recognition receptors that activate inflammasomes in
      macrophages. Inflammasomes are protein platforms essential for the activation of
      inflammatory caspases and subsequent maturation of their pro-inflammatory
      cytokine substrates and induction of pyroptosis. This paper summarizes recent
      developments regarding the function of Nod-like receptors in immunity and
      disease.

PMID- 21083533
TI  - Design optimization of skeletal hip implant cross-sections using finite-element
      analysis.
AB  - The major causes for revision surgery after total hip arthroplasty are aseptic
      loosening, dislocation, wear, design factors, stress shielding on the bone, and
      mechanical and biological factors. A material with toughness and high wear
      properties is essential for a good hip implant because these implants fail due to
      design. Stress shielding is found to be the major cause for the failure of hip
      implants, and can lead to the implant needing to be replaced or revised, which is
      painful for the patient and costly for the health care industry. The hip stem
      designs developed by various manufacturers are solid stems with indentations;
      stems with collars; collarless, tapered stems; and teardrop-shaped, polished
      stems without indentations. They are found to have a greater rigidity, and
      therefore they transfer less load proximally, which results in high proximal
      stress shielding of the proximal femur. A stem of low stiffness alone would not
      suffice in achieving a reduced or optimal stress shielding. The existing design
      proposals to minimize the effect of stress shielding are focused on the use of
      lightweight materials, composite materials, circular and longitudinal hole
      patterns, and different hollow-bore depths. A skeletal hip implant with varying
      cross-sections was designed and finite-element analysis was performed. The
      skeletal hip implant with a hexagonal cross-section was optimized based on the
      mass of the implant and the load-bearing capacity. This lightweight, novel design
      ameliorates implant fixation, minimizes stress shielding, enhances the longevity
      of the implant, and offers better mobility to the patient.

PMID- 21083534
TI  - Health-economic evaluation in implant trials: design considerations.
AB  - In today's world, demonstration of the safety, efficacy, and quality of a new
      treatment strategy is no longer sufficient in many countries for market entry and
      reimbursement in the public healthcare system. This implies that new implants in
      orthopedic and orthopedic trauma surgery not only must be shown to lead to better
      medical outcome compared with the standard of care implant, but also must be
      shown to exhibit "good value" for the money for the public health-care system
      based on sound economic data from health-economic studies. The purpose of this
      article is to elucidate a framework for health-economic aspects alongside implant
      trials, with the assumption that the new implant is more costly but potentially
      better than the control implant. Cost-effectiveness, cost-utility, and cost
      benefit studies are suitable for the assessment of the health-economic value of a
      new implant. The following criteria should be considered for a health-economic
      study design in the context with an implant: i) it should state medical benefits
      of the new implant compared with the control implant; ii) it should precise the
      type of health economic study; iii) it should define the methodological approach,
      perspective of the study, and types of costs; iv) if necessary, it should state
      discount costs and/benefits; and v) a sound sensitivity analysis should be
      included. Furthermore, close cooperation between researchers, clinicians, and
      health economists is essential.

PMID- 21083535
TI  - Side effects of radiation in musculoskeletal oncology.
AB  - Radiation therapy is applied for systemic effects to patients with bone and soft
      tissue tumors and for local effects that facilitate the surgical procedure.
      However, while it remains an essential treatment of cancers, radiation therapy is
      associated with unwanted complications. The purpose of this review is to
      summarize information regarding the complications of radiation in musculoskeletal
      oncology and their management. Because preoperative radiotherapy is associated
      with an increased risk of wound complications and postoperative radiation is
      associated with an increased risk of postradiation fractures, the physician
      requires additional information in deciding on the best method of treatment, and
      such information is provided in this review.

PMID- 21083536
TI  - Periprosthetic fractures of the humerus.
AB  - Classifications have been previously reported and biomechanical studies have been
      performed, but the management of humeral fractures between implants remains
      problematic. At the time of arthroplasty, planning of the optimum length of the
      prostheses is required, especially for patients being considered for a second
      arthroplasty in the ipsilateral elbow or shoulder. Current treatment may be
      conservative if reduction can be obtained and the prostheses are stable, or it
      may be surgical using internal fixation with plates, strut grafts, double plates,
      or a plate and strut graft construct if the fracture extends around the
      components of the prosthesis and autogenous bone grafting.

PMID- 21083537
TI  - Finite element approach used on the human tibia: a study on spiral fractures.
AB  - The application of finite element analysis (FEA) to the field of biomechanics has
      gained immense importance and is helpful in surgical planning and in the design
      of implants. In the pursuit of designing customized and suitable human implants
      to aid in the treatment of fractures, studies analyzing the behavior of bone
      under different loading conditions are required. This paper discusses such a
      study in regard to the human tibia bone, which gets fractured due to twisting
      loading. This spiral fracture phenomenon has been modeled for the evaluation of
      its maximum strain energy-absorbing capacity and Von Mises stresses. A 3D model
      of the human tibia was created from a computed tomography scan using CAD
      software. The model was then imported into FEA software (Femap version 9.0, UGS,
      Plano, TX, USA) and analyzed by applying specific boundary conditions and
      material properties. The results using the FEA approach were then compared with
      those obtained using the conventional method. We hope that these data will be
      helpful for the selection of materials used in medical implants.

PMID- 21083538
TI  - Manufacture of nanoparticles from bone: a preliminary study.
AB  - This study investigated a mechanical processing method using vibratory milling to
      reduce the particle size of bone ash to produce hydroxyapatite (HA) nanoparticles
      from bovine bone. Bovine femurs were cleaned of soft tissue, cut into small
      pieces, heated to 600 deg for 24 h, and ground into a coarse powder. A 50 wt%
      suspension was prepared, vibratory milled for 18 h, and then the milled
      suspension was filter pressed, dried, and ground into powder. The powder was
      analyzed with scanning electron microscopy and X-ray diffraction, which confirmed
      the particle size and the chemical composition of the powder-matched HA. The
      results of this study qualitatively showed that it is possible to produce HA
      nanoparticles from bone. This research explores a "green" manufacturing process
      that reuses a scrap material from the food industry and reduces the use of
      chemical precursors for synthetic nanoparticle synthesis. Such HA powder can
      potentially be used as a bone substitute and for coating orthopedic and dental
      implants.

PMID- 21083539
TI  - The light-harvesting complexes of higher-plant Photosystem I: Lhca1/4 and Lhca2/3
      form two red-emitting heterodimers.
AB  - The outer antenna of higher-plant PSI (Photosystem I) is composed of four
      complexes [Lhc (light-harvesting complex) a1-Lhca4] belonging to the light
      harvesting protein family. Difficulties in their purification have so far
      prevented the determination of their properties and most of the knowledge about
      Lhcas has been obtained from the study of the in vitro reconstituted antennas. In
      the present study we were able to purify the native complexes, showing that
      Lhca2/3 and Lhca1/4 form two functional heterodimers. Both dimers show red
      fluorescence emission with maxima around 730 nm, as in the intact PSI complex.
      This indicates that the dimers are in their native state and that LHCI-680, which
      was previously assumed to be part of the PSI antenna, does not represent the
      native state of the system. The data show that the light-harvesting properties of
      the two dimers are functionally identical, concerning absorption, long-wavelength
      emission and fluorescence quantum yield, whereas they differ in their high-light
      response. Implications of the present study for the understanding of the energy
      transfer process in PSI are discussed. Finally, the comparison of the properties
      of the native dimers with those of the reconstituted complexes demonstrates that
      all of the major properties of the Lhcas are reproduced in the in vitro systems.

PMID- 21083540
TI  - Ketorolac or fentanyl continuous infusion for post-operative analgesia in
      children undergoing ureteroneocystostomy.
AB  - BACKGROUND: children undergoing ureteroneocystostomy suffer from post-operative
      pain due to the surgical incision and bladder spasm. A single-shot caudal block
      is a common technique for paediatric analgesia, but a disadvantage is the
      limitation of a short duration in spite of the additives co-administered. A few
      clinical trials have shown that ketorolac provides an effective post-operative
      analgesia and reduces the bladder spasms after ureteral implantation in children.
      We compared the efficacy of a continuous infusion of ketorolac and fentanyl in
      post-operative analgesia and bladder spasm in children who underwent
      ureteroneocystostomy. METHODS: fifty-two children were allocated to the ketorolac
      group (Group K, n=26) and fentanyl group (Group F, n=26). After general
      anaesthesia, a caudal block was performed with 1.5 ml/kg of 0.15% ropivacaine. At
      the beginning of surgery, an infusion was started after the bolus injection of
      ketorolac 0.5 mg/kg or fentanyl 1 microg/kg. An infusion device was programmed to
      deliver ketorolac 83.3 microg/kg/h or fentanyl 0.17 microg/kg/h for 48 h.
      RESULTS: two of Group F and three of Group K were excluded from the study. Post
      operative pain scores were similar between the two groups. One of Group K (4%)
      and seven of Group F (30.4%) experienced bladder spasms. The rescue analgesic
      requirements were significantly less in Group K. CONCLUSIONS: a Continuous
      infusion of ketorolac provided effective analgesia after operation in children
      who underwent ureteroneocystostomy as well as a low dosage of fentanyl. Ketorolac
      was more effective in reducing the frequency of bladder spasms and rescue
      analgesic requirements.

PMID- 21083541
TI  - Clinical experience of QuantiFERON((r)) -TB Gold testing in patients with
      psoriasis treated with tumour necrosis factor blockers in Taiwan.
AB  - BACKGROUND: In Taiwan, an intermediate tuberculosis burden country, around 9.3%
      of patients with rheumatoid arthritis treated with adalimumab develop
      tuberculosis despite prescreening with the tuberculin skin test. Within the Asia
      Pacific region, the tuberculosis risk in patients with psoriasis who use tumour
      necrosis factor (TNF) blockers is unknown. OBJECTIVES: This study reports the use
      of QuantiFERON((r)) -TB Gold (QFT-G) (Cellestis, Melbourne, Vic., Australia) as a
      screening method for latent tuberculosis infection (LTBI) in patients with
      psoriasis. METHODS: This retrospective review evaluated 216 patients with
      psoriasis in whom TNF blockers were considered between 2004 and 2009 in a
      tertiary referral hospital in Taiwan. Beginning in 2007, QFT-G was performed on
      all patients who were candidates for TNF blockers. RESULTS: Seventeen patients
      who used TNF blockers for less than 4 weeks were excluded. Of the 147 assessed
      patients receiving TNF blockers, 110 (75%) underwent QFT-G tests. A total of 126
      (86%) patients used etanercept and 40 (27%) patients used adalimumab. Nineteen
      patients switched between both. Overall, patients had a median of 24 weeks (range
      4-307) exposure to TNF blockers. Twelve patients (11%) who were treated with TNF
      blockers and eight (15%) without TNF blockers had positive QFT-G results. Of all
      TNF blocker users, only one patient (0.68%) developed tuberculosis. CONCLUSIONS:
      QFT-G can be used to screen for LTBI in a tuberculosis endemic area where bacille
      Calmette-Guerin vaccination coverage is high. Isoniazid prophylaxis is
      recommended for those who have positive QFT-G test results.

PMID- 21083542
TI  - Levels of depression, anxiety and behavioural problems and frequency of
      psychiatric disorders in children with chronic idiopathic urticaria.
AB  - BACKGROUND: Several studies reported that adults with chronic idiopathic
      urticaria (CIU) frequently exhibit psychiatric comorbidity, most commonly
      depression and anxiety disorders. However the literature about children is
      limited. OBJECTIVES: To investigate the frequency of psychiatric disorders and to
      determine the levels of depression, anxiety and behavioural problems in a group
      of children with CIU. METHODS: The study included 27 children with CIU and 27 age
      and sex-matched healthy subjects. Psychiatric assessment was done by using the
      Schedule for Affective Disorders and Schizophrenia for School Age Children
      Present and Lifetime Version (K-SADS-PL). The State-Trait Anxiety Inventory for
      Children (STAI-C), Children's Depression Inventory (CDI) and Child Behavior
      Checklist (CBCL) were used to examine the levels of depression, anxiety and
      behavioural behaviours, respectively. RESULTS: The study group had more frequent
      psychiatric diagnoses than the control group (70% vs. 30%) and the most common
      psychiatric disorders were social anxiety disorder, separation anxiety disorder
      and specific phobia. Depression, trait anxiety, internalizing problems, somatic
      complaints and anxiety/depressed scores were significantly higher in children
      with CIU. No correlation was found between the severity and duration of illness
      and psychological functioning. CONCLUSION: This study showed that children with
      CIU had high psychiatric morbidity. The results suggest that the psychological
      status of children with CIU should be screened by clinicians and that an
      interdisciplinary approach combining dermatological and psychiatric evaluations
      is necessary for the management of CIU.

PMID- 21083544
TI  - Cost-effectiveness of tacrolimus ointment in adults and children with moderate
      and severe atopic dermatitis: twice-weekly maintenance treatment vs. standard
      twice-daily reactive treatment of exacerbations from a third party payer (U.K.
      National Health Service) perspective.
AB  - BACKGROUND: A twice-weekly maintenance treatment regimen with tacrolimus ointment
      for atopic dermatitis (AD) significantly delayed and reduced the number of
      disease exacerbations over a 12-month period compared with the standard reactive
      treatment regimen. OBJECTIVES: To determine the cost-effectiveness of tacrolimus
      ointment used in the maintenance treatment regimen vs. the standard reactive
      treatment regimen for the management of moderate and severe AD in adults and
      children. METHODS: Data from two pivotal phase III studies conducted in adults
      and children receiving 0.1% and 0.03% tacrolimus ointment, respectively, were
      used to populate a decision-analytic model. The costs and benefits associated
      with maintenance vs. reactive use of tacrolimus ointment were calculated over a
      12-month period based on the clinical and quality of life data from the clinical
      trials. The analysis was conducted from the perspective of the U.K. National
      Health Service. Sensitivity analyses were conducted to assess the degree of
      uncertainty surrounding the results. RESULTS: For both adults and children with
      moderate and severe AD, twice-weekly maintenance treatment with tacrolimus
      ointment was shown to be a more effective and less costly (dominant) treatment
      regimen than the standard treatment regimen. Sensitivity analyses demonstrated
      that the model was robust and largely insensitive to changes in model parameters.
      CONCLUSIONS: Maintenance treatment with tacrolimus ointment for the management of
      moderate and severe AD provides incremental health benefits at a lower cost
      compared with the reactive treatment regimen.

PMID- 21083543
TI  - Adalimumab for moderate to severe chronic plaque psoriasis: efficacy and safety
      of retreatment and disease recurrence following withdrawal from therapy.
AB  - BACKGROUND: Adalimumab is effective for moderate to severe chronic plaque
      psoriasis; however, data regarding retreatment following withdrawal and
      subsequent relapse are limited. OBJECTIVES: To evaluate the efficacy and safety
      of adalimumab if interrupted and then resumed in patients with moderate to severe
      psoriasis. METHODS: Patients in a long-term adalimumab open-label extension study
      (NCT00195676) who achieved a Physician's Global Assessment (PGA) score of 'Mild'
      (2), 'Minimal' (1) or 'Clear' (0) were withdrawn from adalimumab and monitored
      for relapse to PGA of 'Moderate' (3) or worse. The subgroup of interest had
      stable psoriasis control, defined as PGA of 0/1 for >=12 weeks on every other
      week (eow) dosing before withdrawal. Relapsing patients were retreated with
      adalimumab (80 mg at week 0 and 40 mg eow starting at week 1). PGA, Psoriasis
      Area and Severity Index responses, fatigue, pharmacokinetics and immunogenicity
      were assessed. RESULTS: In total, 525 patients were withdrawn from adalimumab;
      the subgroup with stable psoriasis control comprised 285 patients. Of these, 178
      relapsed (median=141 days) before treatment reinitiation and 107 did not relapse.
      Patients without relapse by 40 weeks off therapy reinitiated adalimumab. Rates of
      PGA 0/1 after 16 weeks of adalimumab retreatment were 89% for patients without
      relapse and 69% for patients who relapsed. Relapsers experienced significantly
      less fatigue after retreatment. Nine patients (3%) had serious adverse events
      (two were infections). No rebound or allergic reactions occurred. CONCLUSIONS:
      Adalimumab-treated patients who discontinued therapy and subsequently relapsed
      had a good likelihood of regaining clinical efficacy following adalimumab
      reinitiation.

PMID- 21083545
TI  - Primary cutaneous peripheral T-cell lymphoma in a patient with X-linked
      agammaglobulinaemia.

PMID- 21083546
TI  - Primary cutaneous lymphoma: two-decade comparison in a population of 263 cases
      from a Swiss tertiary referral centre.
AB  - BACKGROUND: Epidemiological data on primary cutaneous lymphomas (PCLs) are rare
      and have not previously been investigated in Switzerland. OBJECTIVE: To analyse
      variations in demographics, the pattern of subtypes and staging during the two 10
      year intervals, 1990-1999 and 2000-2009. METHODS: This was a descriptive study of
      263 patients with PCL based on a retrospective review and reassessment according
      to the World Health Organization/European Organization for Research and Treatment
      of Cancer classification. RESULTS: Change was observed in the pattern of
      cutaneous T-cell lymphoma subtypes: the frequency of Sezary syndrome decreased
      from 17% to 7% and the frequency of CD30+ lymphoproliferative disorders increased
      from 7% to 18% (overall P = 0.04). Staging of PCL showed a higher number of cases
      of early-stage mycosis fungoides (P = 0.01). In relation to the international
      data, the Zurich group had a higher number of patients with Sezary syndrome (11%
      vs. 3%) and marginal cell lymphoma (14% vs. 5-7%). In addition, comparison of the
      survival data showed prolonged median overall survival of Zurich patients with
      Sezary syndrome in the second 10-year interval (6.5 vs. 2-4 years). CONCLUSION:
      The increasing frequency of marginal cell lymphoma and CD30+ lymphoproliferative
      disorders might depend on an increased awareness of these diseases in the medical
      community, driven by progress in the classification and staging of these disease
      entities.

PMID- 21083547
TI  - Anticipating the 50th year of Family Process: new initiatives.

PMID- 21083548
TI  - Behavioral couples therapy for the treatment of substance abuse: a substantive
      and methodological review of O'Farrell, Fals-Stewart, and colleagues' program of
      research.
AB  - Behavioral couples therapy (BCT) is an evidence-based couple therapy intervention
      for married or cohabitating substance abusers and their partners. This paper
      provides readers with a substantive and methodological review of Fals-Stewart,
      O'Farrell, and colleagues' program of research on BCT. The 23 studies included in
      this review provide support for the efficacy of BCT for improving substance use
      behavior, dyadic adjustment, child psychosocial outcomes, and reducing partner
      violence. This review includes a description of BCT, summaries of primary and
      secondary outcomes, highlights methodological strengths and weaknesses, notes
      barriers to dissemination, suggests future research directions, and provides
      clinical implications for couple and family therapists. Although there are
      several versions of BCT developed for the treatment of substance abuse this paper
      focuses on the version developed by O'Farrell, Fals-Stewart, and colleagues.

PMID- 21083549
TI  - The efficacy of systemic therapy with adult patients: a meta-content analysis of
      38 randomized controlled trials.
AB  - Systemic therapy is a widely used psychotherapy approach. Yet there exist few
      systematic reviews on its efficacy. A meta-content analysis was performed to
      analyze the efficacy of systemic therapy for the treatment of mental disorders in
      adulthood. All randomized (or matched) controlled trials (RCT) evaluating
      systemic/systems oriented therapy in various settings (family, couple,
      individual, group, multifamily group therapy) with adult index patients suffering
      from mental disorders were identified by database searches and cross-references
      in other reviews. Inclusion criteria were: index patient diagnosed with a DSM or
      ICD listed mental disorder, trial published in any language up to the end of
      2008. The RCTs were content analyzed according to their research methodology,
      interventions applied, and results. Thirty-eight trials published in English,
      German, Spanish, and Chinese were identified, 34 of them showing systemic therapy
      to be efficacious for the treatment of mood disorders, eating disorders,
      substance use disorders, mental and social factors related to medical conditions
      and physical disorders, and schizophrenia. Systemic therapy may also be
      efficacious for anxiety disorders. Results were stable across follow-up periods
      of up to 5 years. There is a sound evidence-base for the efficacy of systemic
      therapy for adult index patients with mental disorders in at least five
      diagnostic groups.

PMID- 21083550
TI  - Disarming jealousy in couples relationships: a multidimensional approach.
AB  - Jealousy is a powerful emotional force in couples' relationships. In just seconds
      it can turn love into rage and tenderness into acts of control, intimidation, and
      even suicide or murder. Yet it has been surprisingly neglected in the couples
      therapy field. In this paper we define jealousy broadly as a hub of contradictory
      feelings, thoughts, beliefs, actions, and reactions, and consider how it can
      range from a normative predicament to extreme obsessive manifestations. We ground
      jealousy in couples' basic relational tasks and utilize the construct of the
      vulnerability cycle to describe processes of derailment. We offer guidelines on
      how to contain the couple's escalation, disarm their ineffective strategies and
      power struggles, identify underlying vulnerabilities and yearnings, and
      distinguish meanings that belong to the present from those that belong to the
      past, or to other contexts. The goal is to facilitate relational and personal
      changes that can yield a better fit between the partners' expectations.

PMID- 21083551
TI  - "Good enough stories": helping couples invest in one another's growth.
AB  - This article utilizes key constructs of the narrative metaphor: that stories
      organize, structure, and give meaning to events in our lives. When stories are
      used as a way to understand the lives of couples, they have the potential for
      enhancing individual and relational growth. It is proposed that knowing both our
      own and our partner's story and development goals increases the likelihood of
      making an investment in self/other and relational growth. It is further suggested
      that helping couples develop narratives with a sense of "We" promotes a more
      generative perspective. These ideas were developed in a small qualitative pilot
      study with long-married, middle-class, heterosexual couples, which suggested that
      the synthesis of each partner's life story into a couple story promoted
      individual and relational development. Implications for therapeutic work with
      couples are presented as well as specific recommendations for ways to utilize the
      life story approach as an aspect of treatment. It is intended to assist
      clinicians and teachers in translating narrative ideas into therapeutic work with
      couples.

PMID- 21083553
TI  - Perceptions of coparenting in foster care.
AB  - Although literature supports the association between harmonious coparenting
      practices and lowered child problems, little is known about coparenting
      influences among family constellations in the foster care system. Via a
      compilation of a new coparenting practices measure, we examined similarities and
      differences on foster parent-derived perceptions of support/flexibility, shared
      communication, conflict/triangulation, and total coparenting between foster and
      biological parents and their independent contribution to child internalizing and
      externalizing problems. Self-reports were gathered from foster parents (N=80) in
      2 groups: kin and nonkin. As compared with nonkin, kin foster parents reported
      higher perceived support/flexibility, shared communication, and total
      coparenting. A tendency for higher conflict/triangulation among kin foster
      parents was also found. After considering foster parent group, psychological
      distress, and harsh discipline, hierarchical regression analyses revealed that
      perceived total coparenting and conflict/triangulation contributed to child
      internalizing and externalizing problems. Results support the linkage between
      perceptions of coparenting and child problems among caregivers (foster and
      biological alike) in kin and nonkin arrangements and highlight training in
      coparenting in general, and conflict management in particular, as an important
      intervention focus to reduce the high level of child problems in this vulnerable
      population.

PMID- 21083552
TI  - A multilevel mediation model of stress and coping for women with HIV and their
      families.
AB  - Families are influential systems and may be an important context in which to
      consider the stress and coping process. To date, many studies have focused on
      modeling the stress and coping process for the individual, isolated from the
      family. The purpose of this secondary analysis was to investigate a cross
      sectional stress and coping model for HIV-positive African-American mothers
      recruited from HIV service facilities in South Florida (n=214) and their family
      members (n=294). Avoidance coping was hypothesized to mediate the relationship
      between stress and psychological distress. In addition, the family average of
      individual stress was hypothesized to moderate the relationship between avoidance
      coping and psychological distress. For all constructs, individuals reported on
      themselves and multilevel modeling techniques were used to account for
      similarities between members of the same family. The estimated mediation effect
      was significant. Aggregated family stress significantly moderated the
      relationship between avoidance coping and psychological distress. This study
      suggests that individuals exhibit different relationships between avoidance
      coping and psychological outcomes and that average stress reported by members of
      a family moderates the relationship between avoidance coping and psychological
      distress.

PMID- 21083554
TI  - Lessons in collaboration, four years post-Katrina.
AB  - Four action researchers present a case study of a project conducted by members of
      a national family therapy organization and members of a local family therapy
      institute, which describes their efforts to collaborate with local disaster
      recovery workers 2 years after Hurricane Katrina. The aim of the collaboration
      was to create a local action research team to study best practices that
      strengthen resilience after disaster. The authors discuss choice points and
      dilemmas faced in finding collaborative partners and in clarifying what
      constitutes an invitation to work in a community. The case study illuminates
      tensions and understandings between outsiders and a community still facing the
      long-term effects of a disaster.

PMID- 21083555
TI  - Adolescents of the USA National Longitudinal Lesbian Family Study: can family
      characteristics counteract the negative effects of stigmatization?
AB  - This investigation examines the impact of homophobic stigmatization on the well
      being of 17-year-old adolescents who were conceived through donor insemination
      and whose mothers enrolled before they were born in the largest, longest-running,
      prospective study of lesbian families, with a 93% retention rate to date. The
      data for the current report were collected through questionnaires completed by
      the adolescents and their mothers. The adolescents (39 girls and 39 boys) were
      queried about family connection and compatibility. They were also asked to
      indicate if they had experienced discrimination based on their mothers' sexual
      orientation. Adolescent well-being was assessed through the parental report of
      the Child Behavior Checklist/6-18. Forty-one percent of the adolescents had
      experienced stigmatization based on homophobia. Hierarchical, multiple-regression
      analyses revealed that stigmatization was associated with more problem behavior
      in these adolescents, but that family compatibility neutralized this negative
      influence. The results indicate that adolescents who have close, positive
      relationships with their lesbian mothers demonstrate resilience in response to
      stigmatization.

PMID- 21083556
TI  - New insights from well responses to fluctuations in barometric pressure.
AB  - Hydrologists have long recognized that changes in barometric pressure can produce
      changes in water levels in wells. The barometric response function (BRF) has
      proven to be an effective means to characterize this relationship; we show here
      how it can also be utilized to glean valuable insights into semi-confined aquifer
      systems. The form of the BRF indicates the degree of aquifer confinement, while a
      comparison of BRFs between wells sheds light on hydrostratigraphic continuity. A
      new approach for estimating hydraulic properties of aquitards from BRFs has been
      developed and verified. The BRF is not an invariant characteristic of a well; in
      unconfined or semi-confined aquifers, it can change with conditions in the vadose
      zone. Field data from a long-term research site demonstrate the
      hydrostratigraphic insights that can be gained from monitoring water levels and
      barometric pressure. Such insights should be of value for a wide range of
      practical applications.

PMID- 21083557
TI  - Inhaled oxygen and cluster headache sufferers in the United States: use, efficacy
      and economics: results from the United States Cluster Headache Survey.
AB  - OBJECTIVE: To present results from the United States Cluster Headache Survey
      concerning the use of inhaled oxygen as acute treatment for cluster headache
      (CH). BACKGROUND: Several small clinic and community-based investigations have
      indicated that more than 50% of CH patients have never used oxygen for the
      treatment of their headaches. This statistic is alarming and the reasons why they
      have not tried oxygen have not been determined. METHODS: The United States
      Cluster Headache Survey is the largest study ever completed looking at CH
      sufferers living in the United States. The total survey consisted of 187 multiple
      choice questions, 84 questions dealt with oxygen use, efficacy and economics. The
      survey was placed on a website from October to December 2008. RESULTS: A total of
      1134 individuals completed the survey (816 male, 318 female). Among them 868
      patients had episodic CH while 266 had chronic CH. Ninety-three percent of survey
      responders were aware of oxygen as a CH therapy; however, 34% had never tried
      oxygen. Forty-four percent of patients had to suggest oxygen to their physicians
      to get prescribed. Twelve percent of physicians refused to prescribe oxygen.
      Fifty percent using oxygen never received training on proper use. Forty-five
      percent had to find their own source for oxygen. On prescriptions only 45%
      specified flow rate, 50% stated CH as diagnosis and 28% indicated mask type.
      Seventy percent of the surveyed population felt oxygen was effective but only 25%
      was presently using oxygen. Potential reasons for this finding include: oxygen is
      slow to onset; prescribed oxygen flow rates are too low for efficacy and most CH
      patients need to raise flow rates during attacks to achieve response. The
      efficacy of oxygen does not vary by the age of the patient, gender, the number of
      CH attacks per day, and smoking history. Episodic CH responds better and faster
      to inhaled oxygen than chronic CH. Oxygen plus a triptan may be more efficacious
      and faster at aborting a CH than a triptan alone. Sixteen percent of CH patients
      state that oxygen is unaffordable while 12% are getting welder grade oxygen
      because of costs of medical grade oxygen, and this form of oxygen could be
      potentially dangerous to the individual user. CONCLUSIONS: Oxygen is
      underutilized by CH patients living in the United States. Current recommended
      oxygen treatment regime is not meeting the needs of many CH patients. Prescribed
      oxygen flow rates are too low for efficacy. Oxygen can be expensive and very
      difficult to obtain. Physicians need to be better educated on the use of inhaled
      oxygen for CH.

PMID- 21083558
TI  - Prophylactic botulinum type A toxin complex (Dysport(r)) for migraine without
      aura.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and optimum dose of a highly
      purified Clostridium botulinum type A toxin-hemagglutinin complex (Dysport) for
      migraine prophylaxis. BACKGROUND: Botulinum toxin type-A has demonstrated good
      efficacy in several open-label studies of patients with migraine, involving
      either individualized or standardized protocols, although data from placebo
      controlled trials have been conflicting. METHODS: A 12-week, double-blind,
      randomized trial of Dysport (120 or 240 units) vs placebo was conducted in 6
      centers in Thailand to evaluate the efficacy, safety, and optimum dose of
      botulinum toxin type-A (Dysport) for migraine prophylaxis. A total of 128
      patients with migraine without aura were enrolled. The primary end point was the
      change in the mean number of migraine attacks per 4-week period from the pre
      treatment period to 8-12 weeks post injection. Secondary efficacy measures
      included the change in the mean total intensity score from the pre-treatment
      period to 8-12 weeks, the investigator and patient global assessments of change
      at each visit compared with pre-treatment, and Migraine Disability Assessment and
      Short Form-36 scores. RESULTS: Change in number of migraine attacks from pre
      treatment to weeks 8-12 was not significantly different. There was a greater
      improvement in total intensity score at weeks 8-12 with Dysport-240 (not
      significant), and interim visit data showed that this was significant at weeks 0
      4 (P = .03 Dysport-240 vs placebo). The mean duration of headache during weeks 0
      4 was lower with Dysport-240 (P = .04 vs placebo). Improvements in patient and
      investigator global assessments of change between weeks 0-4 and 8-12 were
      significant for the Dysport-240 group (both P < .05 vs placebo). CONCLUSIONS:
      Limitations in study design and assessment tools employed may have contributed to
      the inconclusive nature of the primary end point data. Dysport-240 showed
      significant benefit over placebo at some end points and further trials with more
      appropriate outcome measures are required to evaluate effectively this treatment.

PMID- 21083559
TI  - Problem child is no headache.

PMID- 21083561
TI  - Delay discounting of reward in ADHD: application in young children.
AB  - BACKGROUND: A key underlying process that may contribute to attention
      deficit/hyperactivity disorder (ADHD) involves alterations in reward evaluation,
      including assessing the relative value of immediate over delayed rewards. This
      study examines whether children with ADHD discount the value of delayed rewards
      to a greater degree than typically developing children using a delay discounting
      task. METHODS: Children aged 7-9 years diagnosed with ADHD and controls completed
      a task in which they chose between a hypothetical $10 available after a delay (7,
      30, 90 and 180 days) versus various amounts available immediately. RESULTS: ADHD
      participants discounted more steeply than controls. However, this effect did not
      survive covarying of IQ. CONCLUSIONS: ADHD is associated with a steeper delay
      gradient when contemplating hypothetical later rewards, but not independently of
      IQ. The interplay of cognitive processing and IQ with reward evaluation in ADHD
      requires further exploration.

PMID- 21083562
TI  - Annexins.
AB  - Annexins are multifunctional lipid-binding proteins. Plant annexins are expressed
      throughout the life cycle and are under environmental control. Their association
      or insertion into membranes may be governed by a range of local conditions
      (Ca(2+), pH, voltage or lipid identity) and nonclassical sorting motifs. Protein
      functions include exocytosis, actin binding, peroxidase activity, callose
      synthase regulation and ion transport. As such, annexins appear capable of
      linking Ca(2+), redox and lipid signalling to coordinate development with
      responses to the biotic and abiotic environment. Significant advances in plant
      annexin research have been made in the past 2 yr. Here, we review the basis of
      annexin multifunctionality and suggest how these proteins may operate in the life
      and death of a plant cell.

PMID- 21083563
TI  - Sources of variability in canopy reflectance and the convergent properties of
      plants.
AB  - How plants interact with sunlight is central to the existence of life and
      provides a window to the functioning of ecosystems. Although the basic properties
      of leaf spectra have been known for decades, interpreting canopy-level spectra is
      more challenging because leaf-level effects are complicated by a host of stem-
      and canopy-level traits. Progress has been made through empirical analyses and
      models, although both methods have been hampered by a series of persistent
      challenges. Here, I review current understanding of plant spectral properties
      with respect to sources of uncertainty at leaf to canopy scales. I also discuss
      the role of evolutionary convergence in plant functioning and the difficulty of
      identifying individual properties among a suite of interrelated traits. A pattern
      that emerges suggests a synergy among the scattering effects of leaf-, stem- and
      canopy-level traits that becomes most apparent in the near-infrared (NIR) region.
      This explains the widespread and well-known importance of the NIR region in
      vegetation remote sensing, but presents an interesting paradox that has yet to be
      fully explored: that we can often gain more insight about the functioning of
      plants by examining wavelengths that are not used in photosynthesis than by
      examining those that are.

PMID- 21083564
TI  - Rice SIZ1, a SUMO E3 ligase, controls spikelet fertility through regulation of
      anther dehiscence.
AB  - * Sumoylation, a post-translational modification, has important functions in both
      animals and plants. However, the biological function of the SUMO E3 ligase, SIZ1,
      in rice (Oryza sativa) is still under investigation. * In this study, we employed
      two different genetic approaches, the use of siz1 T-DNA mutant and SIZ1-RNAi
      transgenic plants, to characterize the function of rice SIZ1. * Genetic results
      revealed the co-segregation of single T-DNA insertional recessive mutation with
      the observed phenotypes in siz1. In addition to showing reduced plant height,
      tiller number and seed set percentage, both the siz1 mutant and SIZ1-RNAi
      transgenic plants showed obvious defects in anther dehiscence, but not pollen
      viability. The anther indehiscence in siz1 was probably a result of defects in
      endothecium development before anthesis. Interestingly, rice orthologs of AtIRX
      and ZmMADS2, which are essential for endothecium development during anther
      dehiscence, were significantly down-regulated in siz1. Compared with the wild
      type, the sumoylation profile of high-molecular-weight proteins in mature
      spikelets was reduced significantly in siz1 and the SIZ1-RNAi line with notably
      reduced SIZ1 expression. The nuclear localization signal located in the SIZ1 C
      terminus was sufficient for its nuclear targeting in bombarded onion epidermis. *
      The results suggest the functional role of SIZ1, a SUMO E3 ligase, in regulating
      rice anther dehiscence.

PMID- 21083565
TI  - Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force
      report.
AB  - Chronic spontaneous urticaria, formerly also known as chronic idiopathic
      urticaria and chronic urticaria (CU), is more common than previously thought. At
      any time, 0.5-1% of the population suffers from the disease (point prevalence).
      Although all age groups can be affected, the peak incidence is seen between 20
      and 40 years of age. The duration of the disease is generally 1-5 years but is
      likely to be longer in more severe cases, cases with concurrent angioedema, in
      combination with physical urticaria or with a positive autologous serum skin test
      (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on
      quality of life, with sleep deprivation and psychiatric comorbidity being
      frequent. It also has a large impact on society in terms of direct and indirect
      health care costs as well as reduced performance at work and in private life. In
      the majority of patients, an underlying cause cannot be identified making a
      causal and/or curative treatment difficult. Nonsedating H1-antihistamines are the
      mainstay of symptomatic therapy, but treatment with licensed doses relieves
      symptoms effectively in < 50% of patients. Although guideline-recommended
      updosing up to fourfold increases symptom control in many patients, a substantial
      number of patients have only little benefit from H1 -antihistamines.
      Consequently, there is a great need for new therapeutic strategies.

PMID- 21083566
TI  - Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of
      chronic rhinosinusitis--a GA2 LEN study.
AB  - BACKGROUND: The European Position Paper on Rhinosinusitis and Nasal Polyps
      (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the
      clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological
      studies, the definition is based on symptoms only. We aimed to assess the
      reliability and validity of a symptom-based definition of CRS using data from the
      GA(2) LEN European survey. METHODS: On two separate occasions, 1700 subjects from
      11 centers provided information on symptoms of CRS, allergic rhinitis, and
      asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The
      difference in prevalence of CRS between two study points, the standardized
      absolute repeatability, and the chance-corrected repeatability (kappa) were
      determined. In two centers, 342 participants underwent nasal endoscopy. The
      association of symptom-based CRS with endoscopy and self-reported doctor
      diagnosed CRS was assessed. RESULTS: There was a decrease in prevalence of CRS
      between the two study phases, and this was consistent across all centers (-3.0%,
      95% CI: -5.0 to -1.0%, I(2) = 0). There was fair to moderate agreement between
      the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated
      with positive endoscopy in nonallergic subjects, and with self-reported doctor
      diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis.
      CONCLUSION: Our findings suggest that a symptom-based definition of CRS,
      according to the epidemiological part of the EP3OS criteria, has a moderate
      reliability over time, is stable between study centers, is not influenced by the
      presence of allergic rhinitis, and is suitable for the assessment of geographic
      variation in prevalence of CRS.

PMID- 21083567
TI  - Risk of asthma in adult twins with type 2 diabetes and increased body mass index.
AB  - AIM: To examine the relationship between asthma, type 2 diabetes and increased
      body mass index (BMI) in adult twins. METHODS: We performed record linkage
      between questionnaire-defined asthma and BMI, and hospital discharge diagnoses of
      type 2 diabetes in 34,782 Danish twins, 20-71 years of age. RESULTS: The risk of
      asthma was increased in subjects with type 2 diabetes relative to nondiabetic
      subjects both in men (13.5%vs 7.5%), P = 0.001 and in women (16.6%vs 9.6%), P =
      0.001. The result remained significant after adjustment for age, BMI, smoking,
      symptoms of chronic bronchitis, marital status and zygosity, men: OR = 1.70 (1.07
      2.70), P = 0.026; women: OR = 1.88 (1.24-2.85), P = 0.003. In this analysis, BMI
      remained a highly significant predictor for asthma independently of diabetes
      status in women, P < 0.000 but not in men, P = 0.336. Significant positive
      genetic correlations were found between asthma and type 2 diabetes, 0.20 (0.01
      0.40), P = 0.047; between asthma and BMI in women, 0.15 (0.07-0.22), P < 0.000;
      and between BMI and type 2 diabetes, 0.40 (0.29-0.43), P < 0.000. CONCLUSIONS:
      Asthma, type 2 diabetes and increased BMI are strongly associated in adults,
      particularly in women. These results suggest a common aetiology for asthma and
      metabolic syndrome.

PMID- 21083568
TI  - Increase of coagulation potential in chronic spontaneous urticaria.
AB  - BACKGROUND: The pathogenesis of chronic spontaneous urticaria (CU) has recently
      been conceived to be associated with thrombin generation through the extrinsic
      coagulation pathway. However, little is known about the components of the
      intrinsic coagulation pathway potentially involved. METHODS: To investigate the
      whole process of coagulation, both classical coagulation assays and a global
      coagulation test, the intrinsic coagulation pathway-dependent activated partial
      thromboplastin time (APTT) clot waveform analysis, were performed using plasma of
      36 patients with CU who had various severities. RESULTS: Classical coagulation
      assays revealed that levels of fibrinogen, D-dimer, and fibrin and fibrinogen
      degradation products (FDP), and positive rates of soluble fibrin monomer complex
      (SFMC) were significantly elevated in patients with CU, whereas the elevation of
      prothrombin fragment 1 + 2 was not statistically significant. On the other hand,
      all parameters of a global coagulation test, APTT clot waveform analysis,
      evidently showed a hypercoagulable pattern and were significantly correlated to
      disease severity of CU. CONCLUSIONS: CU is characterized by elevated blood
      coagulation potential with involvement of the intrinsic coagulation factors,
      which may contribute in vivo to the generation of fibrin even by small amounts of
      thrombin.

PMID- 21083569
TI  - IgG4 antibodies against rodents in laboratory animal workers do not protect
      against allergic sensitization.
AB  - BACKGROUND: The modified Th2 response, defined as an IgG4 response in the absence
      of IgE, is suggested to protect against the development of allergic
      sensitization. However, studies suggesting this protective effect all had a cross
      sectional design, making it impossible to study the development of both
      responses. AIM OF THE STUDY: We aimed to study the dynamics in IgG4 antibodies in
      relation to allergic sensitization in an occupational cohort of starting
      laboratory animal workers. Moreover, we studied the relation between exposure,
      antibody responses, atopy and self reported allergic symptoms. METHODS: A total
      of 110 starting animal workers were followed for 2 years. IgG4 antibodies against
      rats and mice were assessed. Workers were tested for allergic sensitization and
      exposure to animal allergens was estimated. Symptom status was assessed using
      questionnaires. RESULTS: Rat and mouse specific IgG4 antibodies were present
      before the development of allergy and did not significantly change over time.
      Allergic sensitization was related to exposure and atopic status but high levels
      of IgG4 showed no protective effect. In contrary, workers that developed mouse
      specific sensitization during follow up had higher levels of mouse specific IgG4.
      Symptoms were related to allergic sensitization and IgG4 levels did not influence
      that relationship. CONCLUSIONS: IgG4 antibodies are present before IgE antibodies
      develop and IgG4 levels are stable over time. In our occupational cohort, the
      modified Th2 response had no protective effect on development of sensitization or
      allergic symptoms.

PMID- 21083570
TI  - Microbiota of deciduous endodontic infections analysed by MDA and Checkerboard
      DNA-DNA hybridization.
AB  - AIMS: To evaluate the microbiota of endodontic infections in deciduous teeth by
      Checkerboard DNA-DNA hybridization after uniform amplification of DNA in samples
      by multiple displacement amplification (MDA). METHODOLOGY: Forty samples from the
      root canal system of deciduous teeth exhibiting pulp necrosis with or without
      radiographically detectable periradicular/interradicular bone resorption were
      collected and 32 were analysed, with three individuals contributing two samples;
      these were MDA-amplified and analysed by Checkerboard DNA-DNA hybridization for
      levels of 83 bacterial taxa. Two outcome measures were used: the percentage of
      teeth colonized by each species and the mean proportion of each bacterial taxon
      present across all samples. RESULTS: The mean amount of DNA in the samples prior
      to amplification was 5.2 (+/-4.7) ng and 6.1 (+/-2.3) MUg after MDA. The mean
      number of species detected per sample was 19 (+/-4) (range: 3-66) to the nearest
      whole number. The most prevalent taxa were Prevotella intermedia (96.9%),
      Neisseria mucosa (65.6%), Prevotella nigrescens (56.2%) and Tannerella forsythia
      (56.2%). Aggregatibacter (Haemophilus) aphrophilus and Helicobacter pylori were
      not detected. P. intermedia (10%), Prevotella tannerae (7%) and Prevotella
      nigrescens (4.3%) presented the highest mean proportions of the target species
      averaged across the positive samples. CONCLUSION: Root canals of infected
      deciduous teeth had a diverse bacterial population. Prevotella sp. were commonly
      found with P. intermedia, Prevotella tannerae and Prevotella nigrescens amongst
      the most prominent species detected.

PMID- 21083571
TI  - Viability of human periodontal ligament fibroblasts in milk, Hank's balanced salt
      solution and coconut water as storage media.
AB  - AIM: To evaluate the effectiveness of various storage media at 5  degrees C for
      maintaining the viability of human periodontal ligament fibroblasts (PDLF).
      METHODOLOGY: Plates with PDLF were soaked in recently prepared Hank's balanced
      salt solution (HBSS), skimmed milk, whole milk, Save-A-Tooth((r)) system's HBSS
      (Save), natural coconut water, industrialized coconut water or tap water
      (negative control) at 5  degrees C for 3, 6, 24, 48, 72, 96 and 120 h. Minimum
      essential medium (MEM) at 37  degrees C served as the positive control. PDL cell
      viability was determined by MTT assay. Data were statistically analysed by
      Kruskal-Wallis test complemented by the Scheffe test (alpha=5%). RESULTS: The
      greatest number of viable cells was observed for MEM. Skimmed and whole milk,
      followed by natural coconut water and HBSS, were the most effective media in
      maintaining cell viability (P<0.05). From 24 to 120 h, Save, industrialized
      coconut water and tap water were the worst storage media. CONCLUSIONS: Skimmed
      and whole milk had the greatest capacity to maintain PDLF viability when compared
      with natural coconut water, HBSS, Save, industrialized coconut water and tap
      water.

PMID- 21083572
TI  - Transenamel and transdentinal cytotoxicity of carbamide peroxide bleaching gels
      on odontoblast-like MDPC-23 cells.
AB  - AIM: To evaluate the transenamel and transdentinal cytotoxicity of bleaching gels
      based on carbamide peroxide (CP) on odontoblast-like cells after different
      contact times of the products with enamel. METHODOLOGY: Enamel/dentine discs were
      obtained from bovine incisors and placed in artificial pulp chambers. Bleaching
      gels containing 10% or 16% CP were applied for 8 h day(-1) on the enamel side of
      the discs during periods of 1, 7 or 14 days. Deionized water and artificial
      saliva served as controls. The extracts (culture medium plus bleaching gel
      products that diffused through the discs) were collected and applied on
      previously cultured MDPC-23 cells for 1 h. Cell metabolism was evaluated by the
      MTT assay, and the data were analysed statistically by one-way anova and Tukey's
      test (alpha=0.05). Cell morphology was analysed by SEM. RESULTS: There was no
      significant difference (P>0.05) between the controls and the groups bleached with
      10% CP gel. In the groups bleached with 16% CP gel, however, cell metabolism
      decreased significantly (P<0.05) by 40.32%, 30.16% and 26.61% at 1, 7 and 14
      days, respectively. There was no significant difference (P>0.05) between 1, 7 or
      14 applications of the gels for either of the CP concentrations. CONCLUSION:
      Regardless of the number of applications on an enamel surface, the 10% CP
      bleaching gel did not cause transenamel and transdentinal cytotoxicity to the
      MDPC-23 cell cultures. However, diffusion of products from the 16% CP gel through
      enamel and dentine and cytopathic effects to the pulp cells occurred even after a
      single application of this product on enamel.

PMID- 21083573
TI  - Differential diagnosis of endodontic-related inferior alveolar nerve paraesthesia
      with cone beam computed tomography: a case report.
AB  - AIM: To discuss the use of cone-beam computed tomography (CBCT) in the
      differential diagnosis of a case of labiomandibular paraesthesia caused by
      extrusion of endodontic sealer into the mandibular canal. SUMMARY: A 59-year-old
      woman suffering from a paraesthesia on the left posterior mandible and numbness
      on the left side of the lower lip was referred to an endodontic specialist 1
      month after multiple root canal treatments. A panoramic radiograph revealed the
      presence of extruded root filling material beyond the apex of the mesial root of
      the mandibular left second molar and also beyond the apex of the first premolar.
      A cone beam computed tomography examination was undertaken, which confirmed the
      presence of radiopaque root canal filling material in the periapical area of the
      second molar, and revealed that the material was inside the mandibular canal. No
      extruded filling material was found inside the mental foramen beyond the apex of
      the first premolar tooth. KEY LEARNING POINTS: Small field of view CBCT (where
      possible) can be considered an effective radiographic diagnostic device when
      endodontic-related inferior alveolar nerve or mental foramen paraesthesia are
      suspected. CBCT is able to provide detailed three-dimensional images of the
      tooth, the root canal system and the surrounding tissue.

PMID- 21083574
TI  - Antigen recognition and presentation in periapical tissues: a role for TLR
      expressing cells?
AB  - Bacteria are the prime cause of periapical diseases and root canal microbiology
      is a well-researched area of endodontics. Antigen-presenting cells (APCs) are
      present in periapical lesions of endodontic origin and play a substantial role in
      recognizing, processing and presenting pathogenic antigens to the adaptive immune
      system such as an effective and long-lasting immune response is generated against
      the specific pathogens. Toll-like receptors (TLRs) are germ-line encoded pathogen
      recognition receptors (PRR) expressed by various APCs which induce their
      maturation, lead to gene transcription in the nucleus and the production of
      several pro- and anti-inflammatory cytokines. Thirteen TLRs have been discovered,
      10 of which have been identified in humans so far. Preliminary studies of dental
      pulp tissue have demonstrated various cell types expressing different TLRs in
      response to commonly encountered microorganisms. However, there is little
      information available regarding the expression and function of the various TLRs
      in human periapical lesions. This review discusses the interactions of various
      APCs in periapical lesions and the possible roles of different TLRs and APCs in
      pulp/periapical pathogen recognition and presentation to the adaptive immune
      system in the initiation and sustaining of periapical diseases.

PMID- 21083575
TI  - Diagnostic accuracy of small volume cone beam computed tomography and intraoral
      periapical radiography for the detection of simulated external inflammatory root
      resorption.
AB  - AIM: To compare in an ex vivo model the ability of digital intraoral radiography
      and cone beam computed tomography (CBCT) to detect simulated external
      inflammatory root resorption lesions, and to investigate the effect of altering
      the degree of rotation of the CBCT scanners X-ray source and imaging detector on
      the ability to detect the same lesions. METHODOLOGY: Small and large simulated
      external inflammatory resorption (EIR) lesions were created on the roots of 10
      mandibular incisor teeth from three human mandibles. Small volume CBCT scans with
      180 degrees  and 360 degrees  of X-ray source rotation and periapical
      radiographs, using a digital photostimulable phosphor plate system, were taken
      prior to and after the creation of the EIR lesions. The teeth were relocated in
      their original sockets during imaging. Receiver operator characteristic (ROC)
      analysis and kappa tests of the reproducibility of the imaging techniques were
      carried out and sensitivity, specificity, positive and negative predictive values
      (PPV and NPV) were also determined for each technique. RESULTS: The overall area
      under the ROC curve (Az value) for intraoral radiography was 0.665, compared to
      Az values of 0.984 and 0.990 for 180 degrees  and 360 degrees  CBCT, respectively
      (P<0.001). The sensitivity and specificity of 180 degrees  and 360 degrees  CBCT
      were significantly better than intraoral radiography (P<0.001). CBCT, regardless
      of the degree of rotation, had superior NPVs (P<0.01) and PPVs (P<0.001) to
      periapical radiography. The intra- and inter-examiner agreement was significantly
      better for CBCT than it was for intraoral radiography (P<0.001). The ability of
      small volume CBCT to detect simulated EIR was the same regardless of whether 180
      degrees  or 360 degrees  scans were taken. Examiners were significantly better
      able to identify the exact location of the artificial resorption lesions with
      CBCT than they were with periapical radiographs (P<0.001). CONCLUSION: CBCT is a
      reliable and valid method of detecting simulated EIR and performs significantly
      better than intraoral periapical radiography. Small volume CBCT operating with
      360 degrees  of rotation of the X-ray source and detector is no better at
      detecting small, artificially created EIR cavities than the same device operating
      with 180 degrees  of rotation.

PMID- 21083576
TI  - Multiple idiopathic cervical resorption: case report and discussion of management
      options.
AB  - AIM: To present a case of cervical root resorption affecting all teeth and
      resulting in multiple tooth loss. SUMMARY: A healthy 33-year-old Chinese male,
      with no contributory medical or family/social history, presented with generalized
      cervical root resorption. Lesions varied in severity amongst teeth and even
      involved an impacted third molar. All cervical root surfaces were affected and
      lesions often extended coronally, undermining enamel. CBCT demonstrated that the
      lesions were more extensive and more widely distributed than was seen using
      conventional radiography. Bone extended into many resorptive defects but without
      clinical evidence of ankylosis. Periodontal probing, pulp testing, percussion
      sound and mobility were within normal limits. Key learning points  * Aetiology of
      the generalized idiopathic cervical root resorption is uncertain. * Management is
      complex, and options have included surgical exposure and restoration of affected
      sites, extraction and submergence of affected roots. * A staged approach
      involving early intervention with restoration of resorptive defects, followed by
      progressive extraction and replacement with implant-supported prostheses is
      recommended.

PMID- 21083577
TI  - Accumulated hard tissue debris levels in mesial roots of mandibular molars after
      sequential irrigation steps.
AB  - AIM: To investigate the impact of sequential irrigation procedures on accumulated
      hard tissue debris (AHTD) levels in canal systems in mesial roots of human
      mandibular molars after instrumentation. METHODOLOGY: Based on pre-scans in a
      micro-computed tomography (MUCT) system, 20 extracted human mandibular molars
      with joining mesial root canals and an isthmus between these were selected.
      Canals were instrumented using the ProTaper rotary system until the F3 instrument
      reached working length. A 1% NaOCl solution was applied during instrumentation,
      followed by a final 5-mL flush to working length. Subsequently, canals were
      irrigated with 5 mL of 17% EDTA. Thereafter, passive ultrasonic irrigation (PUI)
      was performed using 1% NaOCl on three occasions each for 20 s. Percent values of
      total canal system volume filled with AHTD were calculated based on high
      resolution scans after each irrigation step. Data was compared using repeated
      measure anova followed by paired t-test for individual comparisons. Bonferroni's
      correction was applied for multiple testing; the alpha-type error was set at 1%.
      RESULTS: Instrumentation of the root canals in conjunction with 1% NaOCl
      irrigation left 6.9 +/- 4.2 vol.% of the total canal system volume filled with
      AHTD. This value was significantly (P < 0.01) reduced to 4.9 +/- 3.6 vol.% after
      EDTA irrigation. Subsequent PUI resulted in a further significant (P < 0.01)
      reduction to 3.7 +/- 2.8 vol.%. CONCLUSIONS: In this quantitative study on AHTD
      reduction, a significant effect of EDTA and PUI was shown. However, approximately
      half of the debris that accumulated during instrumentation remained in the canal
      system.

PMID- 21083578
TI  - Cytotoxicity of set polymer nanocomposite resin root-end filling materials.
AB  - AIM: To evaluate the cytotoxicity of two forms of the novel root-end filling
      materials, polymer nanocomposite (PNC) resins [C-18 Amine montmorillonate (MMT)
      and VODAC MMT] both containing Chlorhexidine Diacetate Salt Hydrate 2%, and to
      compare it to that of two widely accepted commercially available materials,
      ProRoot(r) MTA and Geristore(r). METHODOLOGY: Elutes of experimental materials
      extracted after 24 h, 1, 2 and 3 weeks were interacted with the mouse fibroblasts
      L-929 using a colorimetric cell viability assay (MTS) based on mitochondrial
      dehydrogenases activity. Using 100% and 50% concentrations of the extracted
      elutes of the experimental materials the effect of different concentrations of
      elutes on the cells was analysed. In the positive control group Hygrogold(r) was
      added to the cell culture to arrest cells bioactivity. In the negative control
      group, fresh Dulbecco's Eagle's minimum essential medium supplemented with 10%
      foetal bovine serum was used to enhance cell bioactivity. Differences in mean
      bioactivity values were assessed using a t-test and one-way anova (P<0.05).
      RESULTS: No significant difference was found in cytotoxicity between ProRoot(r)
      MTA, Geristore(r) and PNC resin C-18 Amine MMT on 24 h, 1, 2 and 3 weeks samples.
      Sample elutes of PNC resin VODAC MMT, however, revealed cytotoxic activity during
      most of these experiments. CONCLUSION: Cytotoxicity of the elutes of PNC resin C
      18 Amine MMT was not significantly different from that of ProRoot(r) and
      Geristore(r). PNC resin VODAC MMT, revealed significantly more cytotoxicity
      compared to the other tested materials.

PMID- 21083579
TI  - Effects of estuarine sediment hypoxia on nitrogen fluxes and ammonia oxidizer
      gene transcription.
AB  - The effects of sediment hypoxia, resulting from increased carbon loads or
      decreased dissolved oxygen (DO), on nitrogen cycling in estuarine environments is
      poorly understood. The important role played by bacterial and archaeal ammonia
      oxidizers in the eventual removal of nitrogen from estuarine environments is
      likely to be strongly affected by hypoxic events. In this study, an analysis of
      the effects of different levels of sediment hypoxia (5%, 20% and 75% DO) was
      performed in a microcosm experiment. Changes in the nutrient fluxes related to
      nitrification at 5% DO were observed after 4 h. Quantification of the key
      nitrification gene ammonium monooxygenase (amoA) in both DNA and RNA extracts
      suggests that bacterial amoA transcription was reduced at both of the lower DO
      concentrations, while changes in DO had no significant effect on archaeal amoA
      transcription. There was no change in the diversity of expressed archaeal amoA,
      but significant change in bacterial amoA transcriptional diversity, indicative of
      low- and high-DO phylotypes. This study suggests that groups of ammonia oxidizers
      demonstrate differential responses to changes in sediment DO, which may be a
      significant factor in niche partitioning of different ammonia oxidizer groups.

PMID- 21083580
TI  - Risk of recurrent myocardial infarction with the concomitant use of clopidogrel
      and proton pump inhibitors.
AB  - BACKGROUND: The association between myocardial infarction (MI) and co
      administration of proton pump inhibitors (PPIs) and clopidogrel remains
      controversial. AIM: To quantify the association between concomitant use of PPIs
      and clopidogrel and occurrence of recurrent MI. METHODS: We conducted a case
      control study within a cohort of acute MI patients in PHARMO Record Linkage
      System (1999-2008). The cases were patients readmitted for MI. PPI exposure was
      categorized as current (3-1 days before MI), past (30-3 days before MI), or no
      use (>30 days before MI). We used conditional logistic regression analyses.
      RESULTS: Among 23 655 patients hospitalized following MI, we identified 1247
      patients readmitted for MI. Among clopidogrel users, current PPI use was
      associated with an increased risk of recurrent MI (OR: 1.62, 95% CI: 1.15-2.27)
      when compared with no PPI use, but not when compared with past PPI use (OR: 0.95,
      95% CI: 0.38-2.41). Among clopidogrel non-users, current PPI use was associated
      with an increased risk of recurrent MI (OR: 1.38, 95% CI: 1.18-1.61) when
      compared with no PPI use. CONCLUSIONS: The apparent association between recurrent
      MI and use of PPIs with clopidogrel depends on the design, and is affected by
      confounding by indication. The association is not present when (un)measured
      confounding is addressed by design.

PMID- 21083581
TI  - Review article: medical, surgical and radiological management of perianal Crohn's
      fistulas.
AB  - BACKGROUND: Crohn's anal fistulas are common and cause considerable morbidity.
      Their management is often difficult; medical and surgical treatments rarely lead
      to true healing with frequent recurrence and complications. AIM: To examine
      medical treatments previously and currently used, surgical techniques and the
      important role of optimal imaging. METHODS: We conducted a literature search in
      the Pub Med database using Crohn's, Anal Fistula, Surgery, Imaging and Medical
      Treatment as search terms. RESULTS: Antibiotics and immunosuppressants have a
      role, but slow initial response, side effects and relatively low remission rates
      of up to around a third with frequent recurrence limit their value. Long-term
      infliximab produces clinical remission in 36-58% of patients with combined
      medical and surgical management achieving optimal outcomes. Traditional and newer
      surgical procedures often have a high rate of recurrence with a significant risk
      of temporary or, in up to 10% of cases, permanent stomas, incontinence and
      unhealed or slowly healing wounds in 30%. CONCLUSIONS: Management of Crohn's anal
      fistulas remains challenging. Established principles are to drain infection, use
      setons as required, aggressively manage active proctitis, give antibiotics,
      immunosuppressants and employ anti-TNFalpha therapy, and they demand significant
      co-operation between gastroenterologists and surgeons.

PMID- 21083582
TI  - The effects of itopride on oesophageal motility and lower oesophageal sphincter
      function in man.
AB  - BACKGROUND: Itopride is a new prokinetic agent that combines antidopaminergic and
      cholinesterase inhibitory actions. Previous studies suggested that itopride
      improves heartburn in functional dyspepsia, and decreases oesophageal acid
      exposure in gastro-oesophageal reflux disease. It remains unclear whether this
      effect is due to effects of itopride on the lower oesophageal sphincter (LES).
      AIMS: To study the effects of itopride on fasting and postprandial LES function
      in healthy subjects. METHODS: Twelve healthy volunteers (five men; 32.6 +/- 2.0
      years) underwent three oesophageal sleeve manometry studies after 3 days
      premedication with itopride 50 mg, itopride 100 mg or placebo t.d.s. Drug was
      administered after 30 min and a standardized meal was administered after 90 min,
      with measurements continuing to 120 min postprandially. Throughout the study, 10
      wet swallows were administered at 30-min intervals, and gastrointestinal symptoms
      were scored on 100 mm visual analogue scales at 15-min intervals. RESULTS: Lower
      oesophageal sphincter resting pressures, swallow-induced relaxations and the
      amplitude or duration of peristaltic contractions were not altered by both doses
      of itopride, at all time points. Itopride pre-treatment inhibited the meal
      induced rise of transient LES relaxations (TLESRs). CONCLUSIONS: Itopride
      inhibits TLESRs without significantly affecting oesophageal peristaltic function
      or LES pressure. These observations support further studies with itopride in
      gastro-oesophageal reflux disease.

PMID- 21083583
TI  - Review article: explaining risks of inflammatory bowel disease therapy to
      patients.
AB  - BACKGROUND: Medical treatment for inflammatory bowel disease (IBD) has advanced
      significantly over the past decade, but it is important to communicate
      effectively the balance of benefits and risks of therapy to patients to
      facilitate informed medical decisions. AIM: To review the available data
      describing the risk of side effects of IBD medications and to describe effective
      methods for communicating risk. METHODS: To identify relevant articles for this
      review, a PubMed search was conducted using relevant key words and phrases. In
      addition, reference lists from identified manuscripts were searched and recent
      abstracts from National meetings were reviewed. RESULTS: The steroid-sparing
      medications used for the treatment of IBD all carry risks of both common and rare
      adverse events. Trade-offs need to be made between the risks of these medications
      vs. the risks of poorly treated disease and corticosteroids. There has been
      significant research on how best to present risk data to patients, which is
      summarized in this review. CONCLUSIONS: To ensure that our patients understand
      their choices and feel comfortable with their treatment, we need to communicate
      risk data to patients clearly. Patients comprehend absolute numbers better than
      relative risk, and when available, pictorial representations of data are
      preferred over solely presenting numerical outcomes.

PMID- 21083585
TI  - Randomised clinical trial: the effects of perioperative probiotic treatment on
      barrier function and post-operative infectious complications in colorectal cancer
      surgery - a double-blind study.
AB  - BACKGROUND: Infection following abdominal operation remains a major factor
      affecting the morbidity of patients after surgery. AIM: To determine the effects
      of perioperative administration of probiotics on the gut barrier function and the
      surgical outcome in patients undergoing elective colorectal surgery. METHODS: One
      hundred patients with colorectal carcinoma were randomly divided into the control
      group (n = 50) and the probiotics group (n = 50). The probiotics were given
      orally for 6 days preoperatively and 10 days post-operatively. Outcomes were
      measured by bacterial translocation, gut permeability, the effect on the faecal
      microbiota, and the clinical outcomes such as infectious-related complications
      and gut defecation function. RESULTS: Compared with the control group, probiotics
      group had increased transepithelial resistance (P < 0.05), reduced transmucosal
      permeation of horseradish peroxidase and lactulose/mannitol ratio, reduced
      bacterial translocation (P < 0.05), decreased ileal-bile acid binding protein (P
      < 0.05) and positive rate of blood bacterial DNA (P < 0.05) and an enhanced
      mucosal tight junction protein expression. They had decreased blood
      enteropathogenic bacteria and increased faecal bacterial variety. The post
      operative recovery of peristalsis, incidence of diarrhoea, and infectious-related
      complications were also improved. CONCLUSION: Probiotics can improve the
      integrity of gut mucosal barrier by benefiting the faecal microbiota, and
      decreasing infectious complications in patients with colorectal cancer undergoing
      colorectomy.

PMID- 21083584
TI  - Use and perceived effectiveness of non-analgesic medical therapies for chronic
      pancreatitis in the United States.
AB  - BACKGROUND: Effectiveness of medical therapies in chronic pancreatitis has been
      described in small studies of selected patients. AIM: To describe frequency and
      perceived effectiveness of non-analgesic medical therapies in chronic
      pancreatitis patients evaluated at US referral centres. METHODS: Using data on
      516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we
      evaluated how often medical therapies [pancreatic enzyme replacement therapy
      (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were
      utilized and considered useful by physicians. RESULTS: Oral PERT was commonly
      used (70%), more frequently in the presence of exocrine insufficiency (EI) (88%
      vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses,
      predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42,
      95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of
      PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less
      often (14%) and were more effective in idiopathic and obstructive vs. alcoholic
      chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently
      used (CPB - 5%, octreotide - 7%) with efficacy generally <50%. CONCLUSIONS:
      Pancreatic enzyme replacement therapy is commonly utilized, but is considered
      useful in only subsets of chronic pancreatitis patients. Other medical therapies
      are used infrequently and have limited efficacy.

PMID- 21083586
TI  - Randomised clinical trial: MiraLAX vs. Golytely - a controlled study of efficacy
      and patient tolerability in bowel preparation for colonoscopy.
AB  - BACKGROUND: MiraLAX is gaining acceptance as a bowel cleanser for colonoscopy. We
      hypothesize that MiraLAX/Gatorade is as efficacious for bowel cleansing as
      Golytely and is more tolerable for patients undergoing screening colonoscopy.
      AIM: To compare bowel preparation scores of MiraLAX/Gatorade vs. Golytely and
      examine differences in patient tolerability. METHODS:   Patients undergoing
      screening colonoscopy were randomized to 4 L Golytely or 238 g MiraLAX in 64
      ounces Golytely and four bisacodyl tablets. Efficacy in bowel cleansing was
      assessed using the Boston Bowel Preparation Scale (BPPS). Subjects completed a
      brief survey assessing patient tolerability. RESULTS: A total of 190 patients
      were enrolled (85 male, 105 female; mean age 56.9 years, s.d. 6.3); 87 were
      randomized to MiraLAX, 103 to Golytely. There was no difference in age, gender or
      timing of colonoscopy between the bowel preparation groups. Golytely's median
      total BBPS score was significantly higher than that of MiraLAX [9 (IQR 7-9) vs. 8
      (IQR 6-9), P = 0.034]. Golytely had a higher rate of an excellent equivalent BBPS
      score of 8 or 9 than MiraLAX (70% vs. 55%, P = 0.036). There was no difference in
      patient tolerability (P = 0.857). CONCLUSIONS: Golytely was more efficacious than
      MiraLAX/Gatorade in bowel cleansing; both preparations were equally tolerated by
      patients.

PMID- 21083587
TI  - Chronic fatigue is associated with impaired health-related quality of life in
      inflammatory bowel disease.
AB  - BACKGROUND: Fatigue is reported to reduce health-related quality of life (HRQOL)
      in chronic diseases. Studies on the importance of fatigue and its implications
      for the patient's HRQOL in inflammatory bowel disease (IBD) remain scarce and
      need to be explored. AIM: To investigate the influence of chronic fatigue on both
      generic and disease-specific HRQOL in IBD. METHODS: Patients in remission, with
      mild and moderate IBD completed the Fatigue Questionnaire, the Short-Form 36 (SF
      36) and the Norwegian version of the Inflammatory Bowel Disease Questionnaire (N
      IBDQ). In addition, demographic and clinical variables were obtained. RESULTS: In
      total, 140 patients were included; the mean age of patients with chronic fatigue
      was 44.2 years (s.d. = 15.8), that of nonfatigued was 44.7 years (s.d. = 16.0).
      Ulcerative colitis (UC)/Crohn's disease (CD) = 92/48. Chronic fatigue was
      associated, after controlling for covariates, with a reduction of HRQOL scores in
      6/8 SF-36 dimensions in UC and 5/8 dimensions in CD. In N-IBDQ, chronic fatigue
      was associated with a reduction of HRQOL in four subdimensions and total score in
      CD and all dimensions in UC. CONCLUSIONS: Fatigue is associated with reduction of
      HRQOL scores in IBD. The physical HRQOL domains are particularly affected. The
      impact of fatigue on disability, sick leave, school and work attendance has to be
      studied further.

PMID- 21083588
TI  - Increased proportion of CD16(+) NK cells in the colonic lamina propria of
      inflammatory bowel disease patients, but not after azathioprine treatment.
AB  - BACKGROUND: Distinct functional subsets of natural killer cells potentially
      contribute to the pathology of inflammatory bowel disease (IBD). AIM: To report
      the phenotypic and functional characteristics of natural killer cells in blood
      and lamina propria of IBD patients, and the effect of azathioprine. METHODS:
      Natural killer cells from blood and lamina propria of healthy controls or
      patients with Crohn's disease, or ulcerative colitis were studied by flow
      cytometry. Activation, cytokine production, proliferation and apoptosis of
      natural killer cell subsets were studied in vitro. RESULTS: CD16(+) natural
      killer cells are increased in frequency in the lamina propria comparing Crohn's
      disease or ulcerative colitis with healthy controls. Azathioprine therapy was
      associated with a reduction in total natural killer cells in blood and lamina
      propria, preferentially of the CD16(+) subset. Azathioprine therapy did not
      impair natural killer degranulation, but reduced natural and cytokine-activated
      cytotoxicity and interferon-gamma (IFN-gamma) production. Culture of resting
      peripheral blood mononuclear cells with azathioprine resulted in loss of natural
      killer cells and inhibition of activation and IFN-gamma production. Azathioprine
      preferentially inhibited proliferation of CD16(+) natural killer cells and
      induced apoptosis in resting but not in pre-activated natural killer cells.
      CONCLUSIONS: Natural killer cells with cytolytic potential are enriched in the
      colonic lamina propria of individuals with IBD. Azathioprine is associated with a
      reduction in these cells and a normalization of natural killer cell populations.

PMID- 21083589
TI  - Assessment of liver fibrosis before and after antiviral therapy by different
      serum marker panels in patients with chronic hepatitis C.
AB  - BACKGROUND: Liver biopsy is the reference standard to assess liver fibrosis in
      chronic hepatitis C. AIM: To validate and compare the diagnostic performance of
      non-invasive tests for prediction of liver fibrosis severity and assessed changes
      in extracellular matrix markers after antiviral treatment. METHODS: The
      performances of Forns' score, AST to platelet ratio index (APRI), FIB-4 index and
      Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent
      antiviral therapy. These scores were determined 24 weeks after treatment in 161
      patients. RESULTS: Forns' score, APRI, FIB-4 and ELF score showed comparable
      diagnostic accuracies for significant fibrosis [area under the receiver operating
      characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To
      identify cirrhosis, FIB-4 index showed a significantly better performance over
      APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score
      decreased significantly in patients with sustained virological response (SVR) (P
      < 0.0001) but remained unchanged in nonresponders. Non-1 hepatitis C virus (HCV)
      genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol
      levels were independently associated with SVR. CONCLUSIONS: Simple panel markers
      and ELF score are accurate at identifying significant fibrosis and cirrhosis in
      chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects
      the impact of viral clearance in hepatic extracellular matrix and probably in the
      improvement of liver fibrosis.

PMID- 21083590
TI  - Randomised clinical trial: identification of responders to short-term treatment
      with esomeprazole for dyspepsia in primary care - a randomised, placebo
      controlled study.
AB  - BACKGROUND: Response to proton pump inhibitor (PPI) treatment in dyspepsia is
      unpredictable. AIM: To identify symptoms associated with response to esomeprazole
      in order to target patients for empirical treatment. METHODS: Eight hundred and
      five uninvestigated, primary care patients with upper GI symptoms that were
      considered to be acid-related were randomised to 2 weeks' treatment with
      esomeprazole 40 mg or placebo. The study population was divided into a model
      sample (N = 484) and a validation sample (N = 321). We developed a therapeutic
      index to predict PPI response from the model sample and tested this in the
      validation sample. RESULTS: Response to PPI was found in 68% of patients (44% in
      placebo arm). Bothersome heartburn and early satiety were associated with
      increased likelihood of PPI response, whereas dull abdominal pain, pain relieved
      by bowel movements and nausea in women were associated with a decreased
      likelihood of PPI response. Patients in the validation sample could be classified
      as having a 'very high' (n = 55), 'high' (n = 123), 'medium' (n = 78) or 'low' (n
      = 65) probability of PPI response. The therapeutic gains over placebo were 55%,
      31%, 20% and 22%, respectively. CONCLUSIONS: In patients with uninvestigated
      dyspepsia, PPI responders can be reliably identified by a simple pocket chart
      using symptoms and patient characteristics (ClinicalTrials.gov NCT00318968).

PMID- 21083591
TI  - Classical reflux symptoms, hiatus hernia and overweight independently predict
      pharyngeal acid exposure in patients with suspected reflux laryngitis.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) has been associated with
      reflux laryngitis. AIMS: To investigate the risk factors and the predictors of
      pharyngeal acid reflux (PAR) in Taiwanese patients with suspected reflux
      laryngitis. METHODS: With referral from ENT physicians, 104 patients with
      symptoms and signs suggestive of reflux laryngitis completed a validated symptom
      questionnaire, an upper endoscopy exam and ambulatory 24-h pH tests with three
      sensors located at the hypopharynx, proximal and distal oesophagus. Patients with
      one or more episodes of PAR were considered abnormal. RESULTS: Pharyngeal acid
      reflux was identified in 17% (18/104) of patients. In multivariate logistic
      regression analysis, PAR was independently associated with classical reflux
      symptoms [adjusted odds ratio (aOR) = 3.5, 95% confidence interval (CI): 1.0
      12.8], hiatus hernia (aOR = 6.7, 95% CI: 1.5-30.2) and overweight (aOR = 3.4, 95%
      CI: 1.0-11.0). In predicting PAR, classical reflux symptoms had a sensitivity of
      78% and hiatus hernia had a specificity of 95%. With all three factors, the
      positive predictive value for PAR was 80%. Classical reflux symptoms included
      heartburn, chest pain, dyspepsia and acid regurgitation. CONCLUSIONS: Classical
      reflux symptoms, hiatus hernia and overweight are independent risk factors that
      may predict pharyngeal acid reflux in patients with suspected reflux laryngitis.

PMID- 21083593
TI  - Systematic review: anti-viral therapy of recurrent hepatitis C after liver
      transplantation.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is the first cause of liver
      transplantation worldwide. Recurrence of infection is constant, and compromises
      patient and graft survival. AIM: To provide an updated review of the main
      treatments of recurrent HCV. METHODS: MEDLINE (1990 to August 2010) and national
      meeting abstract search. Search terms included hepatitis C, liver
      transplantation, treatment, sustained virological response. An emphasis was
      placed on randomised trials. RESULTS: Anti-viral therapy based on pegylated
      interferon and ribavirin must be considered before liver transplantation, but is
      poorly tolerated and has poor results in patients with cirrhosis and end-stage
      liver disease or hepatocellular carcinoma. Anti-viral therapy can be
      administrated systematically early after liver transplantation, or in patients
      with established recurrent chronic hepatitis. Combination of pegylated interferon
      alpha plus ribavirin results in a sustained virological response of up to 30% in
      patients with histological HCV recurrence. The results of a small trial of
      polyclonal anti-HCV to prevent recurrence were disappointing. CONCLUSIONS:
      Currently available anti-viral therapy is effective only in a minority of
      transplanted patients infected with HCV. Specifically targeted anti-viral
      therapies combining interferon alpha and ribavirin, or a combination of
      antiprotease and antipolymerase components, associated with a genetic prediction
      of anti-viral response and blocking HCV cell entry should improve the long-term
      prognosis of recurrent hepatitis C in the near future.

PMID- 21083592
TI  - Silymarin use and liver disease progression in the Hepatitis C Antiviral Long
      Term Treatment against Cirrhosis trial.
AB  - BACKGROUND: Silymarin is the most commonly used herbal product for chronic liver
      disease; yet, whether silymarin protects against liver disease progression
      remains unclear. AIM: To assess the effects of silymarin use on subsequent liver
      disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term
      Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis
      and had failed prior peginterferon plus ribavirin treatment. METHODS: Patients
      recorded their use of silymarin at baseline and were followed up for liver
      disease progression (two point increase in Ishak fibrosis score across baseline,
      year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.
      RESULTS: At baseline, 34% of patients had used silymarin, half of whom were
      current users. Use of silymarin was associated (P < 0.05) with male gender;
      oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other
      features. Baseline users had less hepatic collagen content on study biopsies and
      had less histological progression (HR: 0.57, 95% CI: 0.33-1.00; P-trend for
      longer duration of use=0.026). No effect was seen for clinical outcomes.
      CONCLUSIONS: Silymarin use among patients with advanced hepatitis C-related liver
      disease is associated with reduced progression from fibrosis to cirrhosis, but
      has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).

PMID- 21083594
TI  - Bacterial DNA in the diagnosis of spontaneous bacterial peritonitis.
AB  - BACKGROUND: Despite inoculation into blood culture bottles, ascitic fluid culture
      is negative in 50% of cases of spontaneous bacterial peritonitis (SBP). AIM: To
      determine whether 16S rDNA gene detection by real-time polymerase chain reaction
      (PCR) and sequencing increases the efficacy of culture in microbiological
      diagnosis of spontaneous bacterial peritonitis. METHODS: We prospectively
      included 55 consecutive spontaneous bacterial peritonitis episodes in cirrhotic
      patients, 20 cirrhotic patients with sterile ascites and 27 patients with
      neoplasic ascites. Ascitic fluid was inoculated into blood culture bottles at the
      bedside and tested for bacterial DNA by real-time PCR and sequencing of 16S rDNA
      gene. RESULTS: Bacterial DNA was detected in 23/25 (92%) culture-positive SBP,
      16/30 (53%) culture-negative SBP (P = 0.002 with respect to culture-positive
      SBP), 12/20 (60%) sterile ascites (P = 0.01 with respect to culture-positive SBP)
      and 0/27 neoplasic ascites (P < 0.001 with respect to other groups). Sequencing
      identified to genus or species level 12 culture-positive SBP, six culture
      negative SBP and six sterile ascites. In the remaining cases with positive PCR,
      sequencing did not yield a definitive bacterial identification. CONCLUSIONS:
      Bacterial DNA was not detected in almost half the culture-negative spontaneous
      bacterial peritonitis episodes. Methodology used in the present study did not
      always allow identification of amplified bacterial DNA.

PMID- 21083595
TI  - The duration of effect of infliximab maintenance treatment in paediatric Crohn's
      disease is limited.
AB  - BACKGROUND: Infliximab is effective for induction and maintenance of remission in
      children with moderately to severely active Crohn's disease (CD). AIM: To
      evaluate the long-term efficacy of infliximab treatment in paediatric CD.
      METHODS: In this observational, multicentre study, all paediatric CD patients in
      The Netherlands treated with infliximab from October 1992 to November 2009 and
      with minimal follow-up of 3 months since start of infliximab, were studied.
      RESULTS: One hundred and fifty-two CD patients [81M; median age at start of
      infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5
      infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was
      25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative
      probability of losing response to infliximab in patients who initially required
      repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively.
      Seventy-four patients (49%) needed dose adjustments, with a median time to any
      adjustment of 6 months. CONCLUSIONS: Duration of effect of infliximab is limited
      as 50% of patients on infliximab maintenance treatment lose their therapeutic
      response after 5 years. Dose adjustments after start of infliximab are frequently
      needed to regain therapeutic benefit. These findings emphasise the need for
      effective, long-term treatment strategies for paediatric CD.

PMID- 21083598
TI  - How important is peritoneal involvement in rectal cancer? A prospective study of
      331 cases.
AB  - BACKGROUND AND AIMS: The importance of circumferential resection margin
      involvement in predicting locoregional recurrence and death from rectal cancer is
      well known. However, it is well accepted that cases of rectal carcinoma recur
      when this surgical margin is not compromised. The aim of this study was to
      analyse the influence of peritoneal involvement, among other clinicopathological
      variables, on locoregional recurrence and overall prognosis in an unselected
      prospective series of rectal cancer resections. METHODS AND RESULTS: This
      unselected prospective study assessed 331 rectal carcinoma cases from a
      colorectal cancer study that recruited more than 1000 cases. Meticulous
      pathological examination was performed by one pathologist, with particular
      attention paid to the peritoneal surface. All clinicopathological variables were
      entered into a database with comprehensive clinical follow-up. Peritoneal
      involvement was a significant factor in prognosis on univariate analysis but not
      on multivariate analysis. However, in analysing the causes of locoregional
      recurrence specifically, it may have been a factor in causing this in up to half
      the cases. CONCLUSIONS: This study adds to the small amount of literature data on
      the potential importance of peritoneal involvement in predicting locoregional
      recurrence and overall prognosis, especially in upper rectal cancer.

PMID- 21083596
TI  - Randomised clinical trial: a multicentre, double-blind, placebo-controlled study
      on the efficacy and safety of rabeprazole 5 mg or 10 mg once daily in patients
      with non-erosive reflux disease.
AB  - BACKGROUND: The efficacy of rabeprazole 5 mg/day for patients with non-erosive
      reflux disease (NERD) has not been reported in the literature. AIM: To evaluate
      the efficacy of rabeprazole 5 mg and 10 mg/day in Japanese NERD patients. The
      influence of baseline characteristics as well as genetic background on efficacy
      was also analysed. METHODS: Subjects were grade M (minimal changes) NERD
      patients. Two hundred and eighty-eight of these subjects, who were nonresponders
      to open label antacid therapy, entered in a 4-week, double-blind treatment
      (placebo, rabeprazole 5 mg or 10 mg/day). RESULTS: Complete heartburn relief
      rates were 21% in placebo, 34% in rabeprazole 5 mg and 44% in rabeprazole 10 mg
      (5 mg vs. placebo P = 0.074, 10 mg vs. placebo P = 0.001). Rabeprazole 5 mg was
      significantly more effective than placebo in elderly patients and in patients
      with low heartburn frequency or without hiatal hernia. The efficacy of
      rabeprazole 10 mg was not influenced by age, BMI, hiatal hernia, Helicobacter
      pylori infection, frequency and severity of heartburn or CYP2C19 genotypes.
      CONCLUSIONS: Rabeprazole 5 mg was effective in a subgroup of Japanese NERD
      patients. Rabeprazole 10 mg provided more potent heartburn relief than 5 mg and
      was less fragile to baseline characteristics.

PMID- 21083597
TI  - Serum 25-hydroxyvitamin D concentration and physical function in adult men.
AB  - OBJECTIVE: Recent reports suggest that vitamin D status influences
      musculoskeletal health; yet, there are limited data in adult men. This study
      investigated whether serum 25-hydroxyvitamin D [25(OH)D] concentration was
      associated with lean body mass, muscle strength and physical performance in men.
      DESIGN: Population-based, observational survey. PARTICIPANTS: 1219 black,
      Hispanic and white randomly selected men aged 30-79 years from the Boston Area
      Community Health/Bone Survey. MEASUREMENTS: Lean body mass by dual-energy X-ray
      absorptiometry, hand grip strength, a composite physical function score (chair
      stand and walking speed), 25(OH)D, parathyroid hormone (PTH), testosterone, age,
      race, body mass index, socioeconomic status, education, smoking, arthritis, self
      reported health, calcium intake, physical activity. RESULTS: The distributions of
      serum 25(OH)D quartiles differed by race/ethnicity, education and smoking status.
      After adjustment for multiple lifestyle factors, serum 25(OH)D was not related to
      lean body mass, grip strength or the composite physical function score (all
      P>0.20). There was no variation in the associations between 25(OH)D level and
      outcomes by race/ethnicity. The relationship between PTH and the outcomes
      revealed similar results. CONCLUSION: In this population-based sample of adult
      men with a broad age range, there was no association between serum 25(OH)D
      concentration and lean body mass, muscle strength and physical function after
      controlling for multiple lifestyle factors.

PMID- 21083599
TI  - Claudin-7 down-regulation is an important feature in oral squamous cell
      carcinoma.
AB  - AIMS: Claudins, a large family of essential tight junction (TJ) proteins, are
      abnormally regulated in human carcinomas, especially claudin-7. The aim of this
      study was to investigate claudin-7 expression and alterations in oral squamous
      cell carcinoma (OSCC). METHODS AND RESULTS: Expression of claudin-7 was analysed
      in 132 cases of OSCC organized in a tissue microarray. Claudin-7 mRNA transcript
      was evaluated using real-time polymerase chain reaction and the methylation
      status of the promoter was also assessed. Claudin-7 was negative in 58.3% of the
      cases. Loss of claudin-7 protein expression was associated with recurrence (P =
      0.019), tumour size (P = 0.014), clinical stage of OSCC (P = 0.055) and disease
      free survival (P = 0.015). Down-regulation of the claudin-7 mRNA transcripts was
      observed in 78% of the cases, in accordance with immunoexpression. Analysis of
      the methylation status of the promoter region of claudin-7 revealed that
      treatment of O28 cells (that did not express claudin-7 mRNA transcripts) with 5
      Aza-2'-Deoxycytidine (5-Aza-dC) led to the re-expression of claudin-7 mRNA
      transcript. CONCLUSION: Loss of claudin-7 expression is associated with important
      subcellular processes in OSCC with impact on clinical parameters.

PMID- 21083600
TI  - Cytoplasmic expression of survivin is an independent predictor of poor prognosis
      in patients with salivary gland cancer.
AB  - AIMS: The expression of the inhibitor of apoptosis protein survivin has been
      shown to be a significant prognostic indicator in various human cancers. The aim
      was to assess its expression and prognostic value in salivary gland
      adenocarcinoma and muco-epidermoid carcinoma. METHODS AND RESULTS: Survivin
      expression was analysed in 48 patients with parotid gland cancer (21 muco
      epidermoid, 27 adenocarcinomas) by means of immunohistochemistry. The
      experimental findings were correlated with clinicopathological and survival
      parameters. A high cytoplasmic expression of survivin was found in 30% of the
      examined tumours without any significant correlation with the patients'
      clinicopathological characteristics (P > 0.05). Within all patients, the
      estimated overall survival rate of muco-epidermoid carcinomas was significantly
      better than that of adenocarcinomas (P = 0.013). A high cytoplasmic survivin
      expression significantly indicated a poor 5-year disease-free survival rate
      compared to patients with a low cytoplasmic survivin expression in the whole
      group (P = 0.001) and in adenocarcinomas (P = 0.004). In a multivariate analysis,
      a high cytoplasmic survivin expression was the only independent prognostic
      indicator for a significantly poorer 5-year disease-free survival rate (P =
      0.001). CONCLUSIONS: The correlation between cytoplasmic survivin expression and
      survival in salivary gland malignancies might make this an effective tool in
      patient follow-up, prognosis and targeted therapy in future.

PMID- 21083601
TI  - Clinical significance and prognostic value of chromatin assembly factor-1
      overexpression in human solid tumours.
AB  - AIMS: Chromatin assembly factor-1 (CAF-1), whose function is critical for
      maintaining chromatin stability during DNA replication and repair, has been
      identified as a proliferation marker in breast cancer. The aim was to investigate
      CAF-1 as a proliferation marker in a wide variety of solid tumours, and to assess
      its potential value in predicting clinical outcome. METHODS AND RESULTS: Using
      immunocytochemistry on paraffin-embedded tissue sections, the CAF-1 labelling
      index was compared with known proliferation markers Ki-67 and minichromosome
      maintenance (MCM), and its association with clinicopathological data and
      patients' outcome analysed. CAF-1 expression showed a strong positive correlation
      with Ki-67, used routinely to detect proliferating cells, while it generally
      displayed weaker correlations with MCM markers, known to label cells with
      replicative potential. CAF-1 expression was associated significantly with
      histological grade in breast, cervical, endometrial and renal cell carcinomas,
      and with disease stage in endometrial and renal carcinomas. Furthermore, high
      expression of CAF-1 was an independent predictor of adverse clinical outcome in
      renal, endometrial and cervical carcinomas. CONCLUSIONS: CAF-1 is a proliferation
      marker in various malignant tumours with prognostic value in renal, endometrial
      and cervical carcinomas, which supports the value of CAF-1 as a clinical marker
      of cancer progression.

PMID- 21083602
TI  - Immunohistochemical detection of arginine methylated proteins (MeRP) in archival
      tissues.
AB  - AIMS: To (i) determine whether methylarginine-specific antibodies can be employed
      for standard immunohistochemical analysis of paraffin-embedded tissues, (ii)
      analyse methylarginine expression in normal and neoplastic tissues and (iii)
      correlate methylarginine expression with that of protein arginine
      methyltransferase (PRMT1), the predominant cellular arginine methyltransferase.
      METHODS AND RESULTS: Immunohistochemistry of normal and cancer tissues was
      performed utilizing three commercial polyclonal antibodies: anti-methylarginine
      specific antibody (anti-mRG) raised against a methylarginine peptide, Control
      antibody (anti-RG), a control antiserum raised against a corresponding arginine
      peptide without any methylated residues and anti-PRMT1. Nuclear and/or
      cytoplasmic methylarginine expression was detected in all keratinized and non
      keratinized epithelia. A preliminary survey of a series of thyroid, pancreatic,
      colonic and gastric cancers identified a different pattern of methylarginine
      expression in comparison with normal tissue. A correlation between methylarginine
      staining and PRMT1 expression was found in all normal and cancer tissues
      analysed. CONCLUSION: Methylarginine-specific antibodies are capable of
      recognizing methylarginine proteins (MeRP) in paraffin-embedded tissues.
      Methylarginine proteins are expressed widely and show differences in subcellular
      localization in various organs and neoplastic conditions. The efficient detection
      of methylproteins by standard immunohistochemistry provides a new tool to
      investigate the role of methylarginine proteins (MeRP) in biological processes
      including carcinogenesis.

PMID- 21083603
TI  - Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance
      in ovarian epithelial tumours.
AB  - AIMS: The pathological and clinical significance of aberrant miRNA expression in
      ovarian tumours has yet to be adequately documented. The aim of this study was to
      assess the differences in miRNA expression of human ovarian tumours according to
      histological subtype, and to determine whether miRNAs are potential diagnostic
      and prognostic markers in ovarian cancers. METHOD AND RESULTS: The miRNA
      expression profiles of 103 human ovarian tumours were evaluated. Via a bead-based
      miRNA microarray, five aberrant miRNAs were selected which were expressed
      differentially in malignant serous tumours from borderline and benign ovarian
      tumours, including miRNA (miR)-519a, miR-18b (up-regulation) and miR-153, miR-511
      and miR-485-5p (down-regulation). We conducted quantitative real-time reverse
      transcription-polymerase chain reaction (qRT-PCR) in order to confirm that these
      miRNAs are differentially expressed in different histological subtypes of ovarian
      tumours, and compared the expression profiles of these miRNAs between different
      clinical subsets. The expression of these miRNAs was correlated with
      clinicopathological parameters. miR-519a, miR-153 and miR-485-5p were
      differentially expressed in four major histotypes of ovarian cancers (P < 0.05),
      which suggests that they might be of potential importance as diagnostic
      biomarkers. Down-regulation of miR-153 and miR-485-5p was correlated
      significantly with FIGO grade 3 (P < 0.05). Down-regulation of miR-153 and up
      regulation of miR-519a were correlated significantly with advanced clinical stage
      (P < 0.05). The results of Kaplan-Meier survival analysis indicated that the
      higher expression of miR-519a in late stage serous carcinoma was associated
      significantly with poor progression-free survival (P = 0.0058). CONCLUSIONS: A
      significant correlation was detected between the deregulation of specific types
      of miRNAs, such as miR-519a, miR-153 and miR-485-5p, and clinical variables as
      well as histological subtypes in ovarian cancers. Hence, these miRNAs may perform
      functions as diagnostic or prognostic biomarkers.

PMID- 21083604
TI  - Expression of transient receptor potential vanilloid-1 (TRPV1) in urothelial
      cancers of human bladder: relation to clinicopathological and molecular
      parameters.
AB  - AIMS: To evaluate the expression of transient receptor potential vanilloid type-1
      channel protein (TRPV1) in normal and neoplastic urothelial tissues and to
      correlate TRPV1 expression with clinicopathological parameters and disease
      specific survival. METHODS AND RESULTS: TRPV1 expression was analysed in normal
      and neoplastic urothelial samples at both mRNA and protein levels by quantitative
      real time polymerase chain reaction (qPCR) and immunohistochemistry,
      respectively. TRPV1 downregulation was found in urothelial cancer (UC) specimens,
      which correlated with tumour progression. Moreover, TRPV1 mRNA levels were
      associated with clinicopathological parameters to assess the role of TRPV1
      downregulation as a negative prognostic factor for survival. Kaplan-Meier
      survival analysis demonstrated a significantly shorter survival in patients
      showing TRPV1 mRNA downregulation. Multivariate Cox regression analysis indicated
      further that TRPV1 mRNA expression retained its significance as an independent
      risk factor. CONCLUSIONS: The progression of UC of human bladder is associated
      with a marked decrease in TRPV1 expression, with a progressive loss in high-grade
      muscle invasive UC. Downregulation of TRPV1 mRNA expression may represent an
      independent negative prognostic factor for bladder cancer patients.

PMID- 21083605
TI  - Myxoid epithelioid sarcoma: a diagnostic challenge. A report on six cases.
AB  - AIMS: Epithelioid sarcoma (ES) is a distinct sarcoma-type with a specific
      morphology and immunophenotype. Whereas focal myxoid change does occur, to our
      knowledge only two cases of ES with diffuse myxoid stroma have been reported
      previously. To characterize more clearly the myxoid variant of ES, we describe
      six additional cases and discuss the differential diagnoses. METHODS AND RESULTS:
      Cases were retrieved from the authors' files and studied histologically,
      immunohistochemically and by molecular methods. The age of the patients, four
      females and two males, ranged from 16 to 74 years (median: 33 years). The
      neoplasms arose in an extremity (two cases), the abdominal wall, groin, perineum
      and shoulder (one case each). Histologically, four cases were of the conventional
      type, and two were of the proximal type and the immunophenotype was typical for
      ES. The tumour stroma, however, revealed prominent myxoid changes, ranging from
      50 to 90% (median: 75%). Only one of the proximal type ES showed a SMARCB1
      mutation, whereas the other tumours showed no mutation. CONCLUSIONS: The myxoid
      variant of ES represents a diagnostic challenge and may be confused with other
      benign and malignant myxoid neoplasms. The main differential diagnosis is
      myoepithelioma of the skin and soft tissue.

PMID- 21083606
TI  - HER2 gene amplification in primary mucinous ovarian cancer: a potential
      therapeutic target.

PMID- 21083607
TI  - Involvement of LYVE-1-positive endothelial cells in the formation of non
      lymphatic vascular malformations.

PMID- 21083608
TI  - Differential expression of epidermal growth factor receptor in juvenile and adult
      onset recurrent respiratory papillomatosis.

PMID- 21083609
TI  - Clinical significance of the highly sensitive fucosylated fraction of alpha
      fetoprotein in patients with chronic liver disease.
AB  - BACKGROUND AND AIM: The purpose of the present study was to investigate the
      clinical significance of the highly sensitive fucosylated fraction of alpha
      fetoprotein (hs-AFP-L3) in patients with chronic liver disease (CLD) and low
      serum alpha-fetoprotein (AFP) concentration. METHODS: A total of 241 patients
      being treated at our institute with CLD and low serum AFP concentration (3-10
      ng/mL) were investigated retrospectively. We measured total AFP and the
      percentage of AFP-L3 using a uTAS Wako i30 device. The possible presence of
      hepatocellular carcinoma (HCC) was thoroughly investigated by various
      examinations carried out from 1 month before to 1 month after measurements. In
      addition, hs-AFP-L3 elevated and non-elevated groups, divided by the cut-off
      value based on a receiver-operator characteristic (ROC) curve, were followed for
      possible future development of HCC. RESULTS: hs-AFP-L3 was above the detectable
      range in 60 patients (24.9%). Among those AFP-L3 positive cases, 20 (33.3%) were
      found to be HCC prevalent, whereas HCC was found in just 16 patients (8.8%) with
      undetectable hs-AFP-L3 levels. We determined the cut-off value of hs-AFP-L3%,
      which shows the proportion of AFP L3 in total AFP, to be 5.75%. During the follow
      up period, HCC was newly detected in six patients (22.2%) in the hs-AFP-L3%
      elevated group and in 10 (5.6%) in the non-elevated group. Analysis using the
      Kaplan-Meier method showed the HCC-free rate of the hs-AFP-L3% elevated group was
      significantly lower than that of the non-elevated group (P=0.0038). Independent
      predicting variants were female sex (P=0.0024) and hs-AFP-L3% elevation
      (P=0.0036). CONCLUSION: Our results suggest hs-AFP-L3 level is a useful tumor
      marker for HCC in patients with CLD and low serum AFP concentration.

PMID- 21083610
TI  - Epidemiology of lower gastrointestinal bleeding in China: single-center series
      and systematic analysis of Chinese literature with 53,951 patients.
AB  - OBJECTIVES: The epidemiology of lower gastrointestinal bleeding (LGIB) in Western
      populations has been reported; however, there are scant Asian reports. The aim of
      the present study was to determine the etiology of LGIB in a Chinese population
      by reporting a retrospective case series and a systematic analysis of Chinese
      literature. METHODS: A large colonoscopy database in a tertiary endoscopic center
      was searched to identify all patients with the indication of LGIB. The data,
      including patients' sex, age, endoscopic and pathological findings, were
      collected and analyzed. A comprehensive database search of the Chinese literature
      was carried out to obtain all relevant studies. RESULTS: In our series, a total
      of 720 patients with LGIB were included. There were 425 males and 295 females
      with a median age of 50 years, the most common etiologies of LGIB were
      inflammatory bowel disease (IBD; 30.2%), polyps (23.4%) and cancer (10.7%). In
      30.2% of all the patients, no obvious causes were identified. A systematic
      analysis of Chinese literature found an additional 160 studies providing relevant
      data in 53,951 patients. Overall, colorectal cancer (24.4%), colorectal polyps
      (24.1%), colitis (16.8%), anorectal disease (9.8%) and IBD (9.5%) were the most
      common etiologies of LGIB. The main etiologies were different between adults, the
      elderly and children. CONCLUSION: The study shows colorectal cancer, colorectal
      polyps, colitis, anorectal disease and IBD were the most common etiologies of
      LGIB in the Chinese adult and elderly population, whereas colorectal polyps,
      chronic colitis and intussusception were the main causes of LGIB in Chinese
      children. Whereas diverticulum, the most common cause of LGIB in Western
      populations, is uncommon in China.

PMID- 21083611
TI  - Transient elastography: the bigger we are, the harder to scan.

PMID- 21083612
TI  - The first report of homozygous May-Hegglin anomaly E1841K mutation.

PMID- 21083613
TI  - Mind the body in the brain.

PMID- 21083614
TI  - Apoptotic and anti-apoptotic factors in early human mandible development.
AB  - The regulators of apoptosis Bcl-2, Bax, caspase-3, p53, and Hsp70 were analyzed
      immunohistochemically in the developing human mandible of eight human conceptuses
      from weeks 5 to 10 of gestation. During this period, all proteins displayed an
      increased pattern of expression in the mandible ectomesenchyme and in newly
      formed bone, except for caspase-3, which showed decreased expression in the
      ectomesenchyme, but appeared first in the ossification zone at the 7th wk of
      development. Simultaneously, the oral epithelium showed weak (p53) to strong
      (hsp70) expression of all proteins investigated, while in Meckel's cartilage
      cells, bcl-2 was expressed weakly and hsp70 was expressed moderately. Cells on
      the surface of the forming bone were predominantly bax positive, and only
      occasionally bcl-2 positive. Only a few cells on the surface and inside the bony
      spicules co-expressed bax and bcl-2. Terminal deoxynucleotidyl transferase (TdT)
      mediated biotin-dUTP nick-end labelling (TUNEL)-positive cells were found to be
      apoptotic osteoblasts. The expression of all proteins investigated changed
      dynamically during early mandible development and the subsequent differentiation
      of Meckel's cartilage and bone. While interactions between those factors might be
      associated with the survival of Meckel's cartilage, in the ossification zone they
      might participate in the control of cell numbers, mineralization, and bone
      remodelling. Among many other factors, precise orchestration of pro- and anti
      apoptotic factors contributes to normal mandible development.

PMID- 21083615
TI  - Early morphogenesis of heterodont dentition in minipigs.
AB  - The minipig provides an excellent experimental model for tooth morphogenesis
      because its diphyodont and heterodont dentition resemble that of humans. However,
      little information is available on the processes of tooth development in the pig.
      The purpose of this study was to classify the early stages of odontogenesis in
      minipigs from the initiation of deciduous dentition to the late bell stage when
      the successional dental lamina begins to develop. To analyze the initiation of
      teeth anlagens and the structural changes of dental lamina, a three-dimensional
      (3D) analysis was performed. At the earliest stage, 3D reconstruction revealed a
      continuous dental lamina along the length of the jaw. Later, the dental lamina
      exhibited remarkable differences in depth, and the interdental lamina was
      shorter. The dental lamina grew into the mesenchyme in the lingual direction, and
      its inclined growth was underlined by asymmetrical cell proliferation. After the
      primary tooth germ reached the late bell stage, the dental lamina began to
      disintegrate and fragmentize. Some cells disappeared during the process of lamina
      degradation, while others remained in small islands known as epithelial pearls.
      The minipig can therefore, inter alia, be used as a model organism to study the
      fate of epithelial pearls from their initiation to their contribution to
      pathological structures, primarily because of the clinical significance of these
      epithelial rests.

PMID- 21083616
TI  - Expression of prion gene and presence of prion protein during development of
      mouse molar tooth germ.
AB  - In order to gain insight into possible cellular functions of the prion protein
      (PrP) during normal development, the expression of Prnp (encoding the PrP) and
      the distribution of the PrP were studied in murine tooth germs. Expression of
      Prnp in the mouse first molar tooth germ was highly dynamic, increasing several
      fold during the secretory phase of odontogenesis, exhibiting a time-course of
      expression similar to that of genes coding for other extracellular proteins [e.g.
      enamel matrix proteins (Amelx, Ambn, Enam), Aplp1, Clstn1, and Clu]. Western blot
      analysis suggested that the amounts of PrP and amyloid beta (A4) precursor-like
      protein 1 (APLP1) in the tooth germ followed time-courses similar to those of the
      corresponding mRNAs. Immunohistochemical studies of the distribution of PrP in
      murine molar and incisor tooth germs at embryonic day (E)18.5 suggested that this
      protein was located in the cervical loop, outer enamel epithelium, pre
      ameloblasts, and dental papilla. Different degrees of immunolabelling of pre
      ameloblasts on the mesial and distal aspects of a lower molar cusp may be related
      to different enamel configurations on the two aspects. It is concluded that the
      dynamic patterns of expression of Prnp, and of distribution of PrP, suggest that
      PrP may have functions during secretory odontogenesis, perhaps in relation to
      amelogenesis.

PMID- 21083618
TI  - Suppressive effect of the antimicrobial peptide LL-37 on expression of IL-6, IL-8
      and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human
      gingival fibroblasts.
AB  - Porphyromonas gingivalis is a major periodontogenic bacterium and possesses
      immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The
      host antimicrobial peptide, LL-37, suppresses proinflammatory responses of immune
      cells but its effect on human gingival fibroblasts (HGFs) is not known. In this
      study, we assessed the effect of LL-37 on the proinflammatory responses of HGFs
      stimulated with P. gingivalis cells and their components. Live P. gingivalis
      cells did not induce proinflammatory responses of HGFs, and LL-37 did not alter
      these responses. However, LL-37 was able to suppress the killed P. gingivalis
      cell-induced secretion of interleukin (IL)-6 and IL-8. LL-37 also suppressed the
      expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis
      components, including phenol-water extracts, lipid A, and fimbriae, and the
      induction of phosphorylation of p38 and extracellular signal-regulated kinase
      (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed
      in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis
      components. Therefore, LL-37 can exert a suppressive effect on P. gingivalis
      induced proinflammatory responses of HGFs in a paracrine manner, suggesting that
      excess inflammatory responses to P. gingivalis in the gingival tissue are
      suppressed by LL-37 in vivo.

PMID- 21083617
TI  - Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells
      and modulate gene expression in LS8 cells.
AB  - The selective serotonin re-uptake inhibitor (SSRI) fluoxetine is widely used in
      the treatment of depression in children and fertile women, but its effect on
      developing tissues has been sparsely investigated. The aim of this study was to
      investigate if enamel organs and ameloblast-derived cells express serotonin
      receptors that are affected by peripherally circulating serotonin or fluoxetine.
      Using RT-PCR and western blot analysis we found that enamel organs from 3-d-old
      mice and ameloblast-like cells (LS8 cells) express functional serotonin
      receptors, the rate-limiting enzyme in serotonin synthesis (Thp1), as well as the
      serotonin transporter (5HTT), indicating that enamel organs and ameloblasts are
      able to respond to serotonin and regulate serotonin availability. Fluoxetine and
      serotonin enhanced the alkaline phosphatase activity in the cell culture medium
      from cultured LS8 cells, whereas the expression of enamelin (Enam), amelogenin
      (Amel), and matrix metalloproteinase-20 (MMP-20) were all significantly down
      regulated. The secretion of vascular endothelial growth factor (VEGF), monocyte
      chemotactic protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10) was
      also reduced compared with controls. In conclusion, enamel organs and ameloblast
      like cells express functional serotonin receptors. Reduced transcription of
      enamel proteins and secretion of vascular factors may indicate possible adverse
      effects of fluoxetine on amelogenesis.

PMID- 21083619
TI  - Effects of Porphyromonas gingivalis infection on human gingival epithelial
      barrier function in vitro.
AB  - The gingival epithelium plays an important role in the protection of oral tissues
      from microbial challenge. Oral keratinocytes form various cellular contacts,
      including tight junctions, and thus are able to create an epithelial barrier. A
      measurable indicator of barrier function in vitro is the transepithelial
      electrical resistance (TER). Porphyromonas gingivalis is recognized as a major
      aetiologic agent of periodontal disease and exhibits a variety of virulence
      factors. The aim of the study was to investigate the effect, in vitro, of
      infection with P. gingivalis on gingival barriers composed of primary and
      immortalized human keratinocytes. Primary and immortalized human gingival
      keratinocytes were infected with different strains of P. gingivalis. The impact
      of the bacterial challenge on the barrier was analysed by measuring the TER. The
      destructive effects of gingipains were blocked by specific enzyme inhibitors.
      After an initial increase of about 20-30% in infected wells, the TER decreased to
      zero. Gingipain inhibitors delayed the destruction of the barrier by 12 +/- 4 h.
      In all cases, the loss of TER was accelerated if the system was infected from the
      basolateral side. A distinct effect of P. gingivalis on the epithelial barrier
      function of three-dimensional cultured epithelial cell models was demonstrated,
      which can partly be attributed to the activity of gingipains.

PMID- 21083620
TI  - Molecular force probe measurement of antigen I/II-matrix protein interactions.
AB  - Viridans streptococci possess a family of immunologically and structurally
      related cell-surface proteins, termed antigen I/II, which may function as
      adhesins and enable oral streptococci to adhere to saliva-coated surfaces and
      matrix proteins. Here we used atomic force microscopy in the molecular force mode
      to measure the specific interaction forces between antigen I/II and two matrix
      proteins, collagen and fibronectin. These matrix proteins provide important
      binding sites for adherence of oral streptococcal in dentinal caries and
      endocarditis, respectively. Antigen I/II-coated cantilever tips were brought into
      contact with collagen- or fibronectin-coated silica coverslips. For the protein
      I/II-fibronectin interaction experiments, the mean strength of the last ruptures
      was 216 pN, with most of the detachments located around 125 pN. In antigen I/II
      collagen interaction experiments, the mean strength of the last rupture forces
      corresponded to 136 pN, with the most frequent unbinding force around 75 pN.
      Thus, our findings definitely suggest that, under the present experimental
      conditions, antigen I/II binds more strongly to fibronectin than to type I
      collagen. This might be of relevance for the attachment of viridians streptococci
      to surfaces exposed to strong hydrodynamic shearing forces under in vivo
      conditions.

PMID- 21083621
TI  - Experimental orthodontic tooth movement and extensive root resorption:
      periodontal and pulpal changes.
AB  - Previous studies have reported changes both in dental pulp and in periodontal
      ligament (PDL) following orthodontic tooth movement. However, pulpal changes
      following extensive root resorption after orthodontic tooth movement have not
      been studied in detail. The aim of this study was therefore to evaluate
      inflammatory changes, both in the dental pulp and in the compressed PDL, after
      experimentally induced extensive root resorption. Extensive root resorption was
      induced in rats by the activation and re-activation of orthodontic force, with a
      short intervening period of no force application. The distribution of immune
      cells, nerve fibres and blood vessels was studied immunohistochemically using
      antibodies against CD68-immunoreactive (IR) cells, major histocompatibility
      complex (MHC) class II Ia-expressing cells, CD43-IR cells, protein gene product
      9.5 (PGP 9.5), and laminin. In the compressed PDL of experimental first molars,
      significantly increased density of CD68-IR cells and MHC class II Ia-expressing
      cells were found, whereas the density of CD43-IR cells were unchanged when
      compared with control second molars. In the compressed PDL, there was an
      increased density of blood vessels, but no sprouting of nerve fibres. In the
      dental pulp, however, no increased density of immune cells or sprouting of nerve
      fibres was recorded. In conclusion, inflammation after extensive root resorption
      was confined to the compressed PDL, whereas the dental pulp was unaffected.

PMID- 21083622
TI  - Human and bovine enamel erosion under 'single-drink' conditions.
AB  - Tooth-surface pH is lowered, during drinking, to a value close to the pH of the
      drink itself. After the drink is swallowed, the pH rises to baseline values but
      this process can take several minutes. Few techniques can quantify enamel erosion
      at timescales representative of single drinks. The objective of this study was to
      compare human and bovine erosion over acid-exposure times of 2 s to 1 h. Human
      and bovine enamel softening was compared in vitro using nanoindentation (2-60 s
      of exposure to acid) and tissue loss was compared using optical profilometry (1
      60 min of exposure to acid). Nanoindentation revealed statistically significant
      softening after 2 s (human) and 5 s (bovine); there were no significant
      differences in hardness reduction for the two tissues at any time-point.
      Profilometry demonstrated statistically significant tissue loss after 20 min
      (human) and 10 min (bovine); bovine tissue loss progressed 30% faster than human
      tissue loss. These results support the use of bovine enamel as a substitute for
      human enamel in erosion studies, with the understanding that for moderate
      exposure times bovine enamel erodes 30% faster than human enamel. Nanoindentation
      can be used to detect enamel dissolution at timescales comparable to the oral
      dwell-time of a single 'mouthful' of a beverage.

PMID- 21083623
TI  - Effects of casein phosphopeptide amorphous calcium fluoride phosphate paste on
      white spot lesions and dental plaque after orthodontic treatment: a 3-month
      follow-up.
AB  - The effects of casein phosphopeptide amorphous calcium fluoride phosphate (CPP
      ACFP) paste vs. control paste on the remineralization of white spot caries
      lesions and on plaque composition were tested in a double-blind prospective
      randomized clinical trial. Fifty-four orthodontic patients, with multiple white
      spot lesions observed upon the removal of fixed appliances, were followed up for
      3 months. Subjects were included and randomly assigned to either CPP-ACFP paste
      or control paste, for use supplementary to their normal oral hygiene. Caries
      regression was assessed on quantitative light-induced fluorescence (QLF) images
      captured directly after debonding and 6 and 12 wk thereafter. The total counts
      and proportions of aciduric bacteria, Streptococcus mutans, and Lactobacillus
      spp. were measured in plaque samples obtained just before debonding, and 6 and 12
      wk afterwards. A significant decrease in fluorescence loss was found with respect
      to baseline for both groups and no difference was found between groups. The size
      of the lesion area did not change significantly over time or between the groups.
      The percentages of aciduric bacteria and of S. mutans decreased from 47.4 to
      38.1% and from 9.6 to 6.6%, respectively. No differences were found between
      groups. We observed no clinical advantage for use of the CPP-ACFP paste
      supplementary to normal oral hygiene over the time span of 12 wk.

PMID- 21083624
TI  - Migration background: a risk factor for caries development during adolescence.
AB  - The influence of child and parental migration background on the risk of
      approximal caries increment in Swedish adolescents was investigated. This
      retrospective longitudinal register-based cohort study included all 13-yr-old
      adolescents (n = 18,142) who were resident in the County of Stockholm, Sweden, in
      2000, and followed them up to 19 yr of age. At follow-up, 15,538 subjects were
      examined. Caries data [decayed, missing, and filled teeth/surfaces (DMFT/S)],
      were collected from a dental database. Socio-demographic determinants were
      collected from Swedish National Registers. After adjustments for socio
      demographic confounders, logistic regression analysis revealed that adolescents
      with foreign-born parents, irrespective of whether the child was born in Sweden
      or abroad, exhibited a significantly elevated risk for approximal caries
      increment (DMFSa > 0), and developed, on average, 0.53 and 1.14 more approximal
      caries lesions, respectively, compared with their counterparts with Swedish-born
      parents. Furthermore, adolescents born in eastern Europe exhibited an increased
      risk for approximal caries increment (DMFSa > 0) and developed, on average, 1.06
      more approximal caries lesions compared with Swedish-born adolescents. In
      conclusion, parental migration background must be considered as a risk factor for
      caries development during adolescence, irrespective of whether or not the
      adolescent was born in Sweden.

PMID- 21083625
TI  - Changes in the quality of life of Tanzanian school children after treatment
      interventions using the Child-OIDP.
AB  - This study aimed to examine the evaluative properties of the Child Oral Impacts
      on Daily Performances (Child-OIDP) inventory and to estimate treatment-associated
      changes in the OIDP and self-reported oral health following atraumatic
      restorative treatment (ART) and oral health education (OHE). A total of 1,306
      school attendees in Kilwa, Tanzania, completed the Child-OIDP inventory before,
      and 6 months after, treatment. The post-treatment questionnaire assessed change
      in perceived oral health. Complete baseline and follow-up data were obtained for
      104, 117, and 1,085 participants who received, respectively, ART fillings (Group
      A), ART fillings and tooth extraction (Group B), and OHE only (Group C). The
      longitudinal validity, responsiveness, and treatment-associated changes were
      calculated using anova, effect sizes, and repeated general linear models (GLM).
      The follow-up prevalence was 73.8%. The mean changes in the OIDP total- and
      subscale scores were negative within those who reported 'worsened' oral health,
      and positive in subjects reporting 'improved' oral health. Effect sizes for the
      total OIDP score ranged from -0.2 within the category 'worsened' to 0.4 within
      the category 'improved'. Changes following treatment were more extensive in Group
      B compared with Groups A and C, and in Group C compared with Group A. The Child
      OIDP showed promising evaluative properties and responsiveness to change
      following ART fillings, ART fillings and tooth extraction, and OHE.

PMID- 21083626
TI  - Comparison of cerebral activity during teeth clenching and fist clenching: a
      functional magnetic resonance imaging study.
AB  - Using functional magnetic resonance imaging (fMRI), we compared the cerebral
      activity during bilateral light fist-clenching and light-teeth clenching to
      provide more information on the central processing mechanisms underlying awake
      bruxism. Fourteen subjects participated in our study. Statistical comparisons
      were used to identify brain regions with significant activation in the
      subtraction of light fist clenching and light teeth clenching activity minus
      baseline. Participants also evaluated the perceived effort of clenching for each
      task, using a visual analogue scale of 0-100, after fMRI was performed. Bilateral
      light fist-clenching significantly activated the bilateral sensorimotor cortex,
      while light teeth-clenching was significantly associated with activation of the
      bilateral sensorimotor cortex, supplementary motor area, dorsolateral prefrontal
      cortex, and posterior parietal cortex. The VAS scores for fist clenching and
      teeth clenching were not significantly different. As light teeth-clenching
      activates a more extensive cortical network compared with light fist-clenching,
      we suggest that the teeth clenching may induce a more complex cerebral activity
      compared with the performance of a hand motor task. The clinical significance of
      these findings remains unknown but could perhaps be related to the propensity to
      trigger awake bruxism.

PMID- 21083627
TI  - Latent variable approach to correct errors in radiographic measurements.
AB  - Radiographic outcomes are important for the diagnosis and treatment of
      periodontal diseases. However, the assessment of radiographic measurements is
      affected by many factors, and it is therefore difficult to ascertain changes in
      radiographic outcomes. In this study, we proposed a latent variable approach to
      correct for the distortion in the radiographic measurements in pairs of
      periapical radiographs taken before and after periodontal treatment. Clinical
      data from 123 patients treated with non-surgical periodontal therapy was used to
      illustrate the latent variable approach in assessing radiographic changes in
      infrabony defect depth. Results were compared with a correction factor method.
      Computer simulations were also undertaken to evaluate the performance of these
      two methods compared with uncorrected, raw measurements by calculating their
      intraclass correlation coefficients (ICCs). The example data set showed that the
      latent variable method (LVM) and the correction factor method (CFM) were
      comparable. Simulations showed that both methods achieved very high ICCs in
      different scenarios, whilst uncorrected raw measurements had relatively low ICCs.
      This study suggests that correction for errors in radiographic measurements is
      required for routine radiographs. Whilst both LVM and CFM achieve excellent
      results, LVM is more flexible in handling missing values, and may provide better
      results when treatment effects are large.

PMID- 21083628
TI  - Brain death provokes very acute alteration in myocardial morphology detected by
      echocardiography: preventive effect of beta-blockers.
AB  - Our objective was to evaluate immediate acute changes in myocardial function
      during the autonomic storm of brain death (BD). Wistar rats were divided into
      four groups (n = 8/group): controls without any treatment, beta-blocker
      (Esmolol(r), 10 mg/kg), calcium channel blocker (Diltiazem(r), 10 mg/kg), or
      alpha-blocker (Prazosin(r), 0.3 mg/kg). Treatments were administered
      intravenously 5 min before BD induction. Echocardiography (ATL-5000, 8 MHz) was
      performed to measure left ventricular (LV) dimensions and fractional shortening
      at baseline, during BD induction and 5 min and 15 min after BD. In controls, BD
      was immediately associated with an increase in wall thickness and a decrease in
      LV cavity dimension. This myocardial wall hypertrophy was completely prevented by
      beta-blockers, but not with calcium- and alpha-blockers. Extensive myocardial
      interstitial edema was found in all groups, except in the beta-blocker group.
      Myocardial wall hypertrophy was also prevented during a longer follow-up of 180
      min after BD in beta-blocker group as opposed to controls. In conclusion, BD is
      associated with an immediate and severe myocardial damage related to an important
      interstitial edema which is prevented by beta-blockers.

PMID- 21083629
TI  - Isolation and characterisation of prolactin-releasing peptide in chicks and its
      effect on prolactin release and feeding behaviour.
AB  - Prolactin (PRL)-releasing peptides (PrRP) have been identified in mammals,
      amphibians and fishes, and these animals have several PrRPs that consist of
      different numbers of amino acids such as 20, 31 and 37. In the present study, we
      identified the cDNA encoding chicken prepro-PrRP, which can generate putative
      PrRPs, and cloned and sequenced it. Sequences for the coding region suggested the
      occurrence of putative PrRPs of 20, 31 and 32 amino acid residues. The amino acid
      sequence of chicken PrRP20 showed 100%, 95% and 70% identity with those of
      PrRP20s from teleosts, Xenopus laevis and mammals, respectively. On the other
      hand, chicken PrRP31 showed approximately 90% and 52-55% homology to PrRP31s of
      X. laevis and mammals, respectively. Native chicken PrRPs were purified from an
      acid extract of chick brain by a Sep-Pak C18 cartridge (Waters Corp., Milford,
      MA, USA), affinity chromatography using anti-salmon PrRP serum, and reverse phase
      high-performance liquid chromatography (HPLC) on an ODS-120T column (TOSOH,
      Tokyo, Japan). The existence of chicken PrRP20 and PrRP31 in the brain was
      demonstrated by comparing them with the synthetic peptides using HPLC and matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry. Chicken
      PrRP31 increased plasma PRL concentration when administered peripherally, whereas
      central administration decreased the concentration, suggesting that chicken
      PrRP31 has a distinct effect on PRL secretion between tissues in chicks. On the
      other hand, plasma growth hormone concentration decreased with both peripheral
      and central administrations of chicken PrRP31. Furthermore, central
      administration of chicken PrRP31 increased food intake in chicks compared to
      those observed in mammals and fishes. Taken together with the results indicating
      that chicken PrRP20 did not show endocrine and behavioural effects, we showed
      that chicken PrRP has a similar amino acid sequence to teleosts, Xenopus laevis
      and mammals, although the actions were variable among vertebrates.

PMID- 21083630
TI  - Modelling the in vivo spike activity of phasically-firing vasopressin cells.
AB  - A minimalist model of magnocellular vasopressin neurones was developed to examine
      the hypothesis that their phasic behaviour is the product of intrinsic voltage-
      and activity-dependent intracellular mechanisms that create a bistable dynamical
      system. The model can closely match a range of phasic behaviours recorded in
      vasopressin cells in vivo, as well as reproduce the three archetypal behaviours
      of vasopressin cells (continuous firing, sparse sporadic firing and phasic
      firing) by varying one of the fourteen model parameters. In addition, the mean
      and standard deviation of burst and silence periods can be matched by varying a
      further two parameters. In the model, the long-term behaviour (phasic
      characteristics) of cells is largely independent of the short-term behaviour
      (interspike intervals).

PMID- 21083631
TI  - Temporal effect of adrenocorticotrophic hormone on adrenal glucocorticoid
      steroidogenesis: involvement of the transducer of regulated cyclic AMP-response
      element-binding protein activity.
AB  - The availability of active steroidogenic acute regulatory protein (StAR) and side
      chain cleavage cytochrome P450 (P450scc) are rate-limiting steps for
      steroidogenesis. Transcription of StAR and P450scc genes depends on cyclic AMP
      response element-binding protein (CREB) phosphorylation and CREB co-activator,
      transducer of regulated CREB activity (TORC), which is regulated by salt
      inducible kinase 1 (SIK1). In the present study, we investigated the relationship
      between TORC activation and adrenocorticotrophic hormone (ACTH)-induced
      steroidogenesis in vivo, by examining the time-course of the effect of ACTH
      injection (4 ng, i.v.) on the transcriptional activity of StAR and P450scc genes
      and the nuclear accumulation of transducer of regulated CREB activity 2 (TORC2)
      in rat adrenal cortex. ACTH produced rapid and transient increases in plasma
      corticosterone, with maximal responses between 5 and 15 min, and a decrease to
      almost basal values at 30 min. StAR and P450scc hnRNA levels increased 15 min
      following ACTH and decreased toward basal values at 30 min. Concomitant with an
      increase in nuclear phospho-CREB, ACTH injection induced nuclear accumulation of
      TORC2, with maximal levels at 5 min and a return to basal values by 30 min. The
      decline of nuclear TORC2 was paralleled by increases in SIK1 hnRNA and mRNA 15
      and 30 min after injection, respectively. The early rises in plasma
      corticosterone preceding StAR and P450scc gene transcription suggest that post
      transcriptional and post-translational changes in StAR protein mediate the early
      steroidogenic responses. Furthermore, the direct temporal relationship between
      nuclear accumulation of TORC2 and the increase in transcription of steroidogenic
      proteins, implicates TORC2 in the physiological regulation of steroidogenesis in
      the adrenal cortex. The delayed induction of SIK1 suggests a role for SIK1 in the
      declining phase of steroidogenesis.

PMID- 21083633
TI  - Cultural inheritance drives site fidelity and migratory connectivity in a long
      distance migrant.
AB  - Cultural transmission is thought to be a mechanism by which migratory animals
      settle into habitats, but little evidence exists in wild populations because of
      the difficulty of following individuals over successive generations and wide
      geographical distances. Cultural inheritance of migration routes represents a
      mechanism whereby geographical isolation can arise between separate groups and
      could constrain individuals to potentially suboptimal sites within their range.
      Conversely, adopting the parental migratory route in adult life, rather than
      dispersing randomly, may increase an individual's reproductive success because
      that strategy has already been proven to allow successful breeding. We combined a
      pedigree of related light-bellied Brent geese (Branta bernicla hrota) with 6
      years of observations of marked birds to calculate the dispersal distances of
      adult offspring from their parents in both Ireland and Iceland. In both
      countries, the majority of offspring were found to recruit into or near their
      parental sites, indicating migratory connectivity in the flyway. Despite this kin
      structure, we found no evidence of genetic differentiation using genotype data
      from 1127 individuals across 15 microsatellite loci. We suggest that the
      existence of migratory connectivity of subpopulations is far more common than
      previous research indicates and that cultural information may play an important
      role in structuring reproductive isolation among them.

PMID- 21083634
TI  - Involvement of IbeA in meningitic Escherichia coli K1-induced polymorphonuclear
      leukocyte transmigration across brain endothelial cells.
AB  - Transmigration of neutrophil [polymorphonuclear neutrophil (PMN)] across the
      blood-brain barrier (BBB) is a critical event in the pathogenesis of bacterial
      meningitis. We have shown that IbeA is able to induce meningitic Escherichia coli
      invasion of brain microvascular endothelial cells (BMECs), which constitutes the
      BBB. In this report, we provide evidence that IbeA and its receptor, vimentin,
      play a key role in E. coli-induced PMN transmigration across BMEC. In vitro and
      in vivo studies indicated that the ibeA-deletion mutant ZD1 was significantly
      less active in stimulating PMN transmigration than the parent strain E44. ZD1 was
      fully complemented by the ibeA gene and its product. E. coli-induced PMN
      transmigration was markedly inhibited by withaferin A, a dual inhibitor of
      vimentin and proteasome. These cellular effects were significantly stimulated and
      blocked by overexpression of vimentin and its head domain deletion mutant in
      human BMEC, respectively. Our studies further demonstrated that IbeA-induced PMN
      migration was blocked by bortezomib, a proteasomal inhibitor and correlated with
      upregulation of endothelial ICAM-1 and CD44 expression through proteasomal
      regulation of NFkappaB activity. Taken together, our data suggested that IbeA and
      vimentin contribute to E. coli K1-stimulated PMN transendothelial migration that
      is correlated with upregulation of adhesion molecule expression at the BBB.

PMID- 21083635
TI  - Evening circadian oscillator as the primary determinant of rhythmic motivation
      for Drosophila courtship behavior.
AB  - Circadian clocks of Drosophila melanogaster motivate males to court females at a
      specific time of day. However, clock neurons involved in courtship rhythms in the
      brain of Drosophila remain totally unknown. The circadian locomotor behavior of
      Drosophila is controlled by morning (M cells) and evening (E cells) cells in the
      brain, which regulate morning and evening activities, respectively. Here, we
      identified the brain clock neurons that are responsible for the circadian rhythms
      of the close-proximity (CP) behavior that reflects male courtship motivation.
      Interestingly, the ablation or functional molecular clock disruption of E cells
      caused arrhythmic CP behavior, but that of M cells resulted in sustained CP
      rhythms even in constant darkness. In addition, the ablation of some dorsal
      lateral neurons (LNd) of E cells using neuropeptide-F (NPF)-GAL4 did not impair
      CP rhythms. These findings suggested that the NPF-negative LNds and DN1s of E
      cells include cells essential for circadian CP behavior in Drosophila.

PMID- 21083636
TI  - PKC-dependent endocytosis of the Helicobacter pylori vacuolating cytotoxin in
      primary T lymphocytes.
AB  - Gastric infection by Helicobacter pylori (Hp) is associated with development of
      gastritis, ulcerations and gastric adenocarcinoma. Production and secretion of
      the vacuolating cytotoxin (VacA) is an essential Hp virulence factor. VacA is a
      multifunctional toxin, which exerts immunosuppressive effects on human T
      lymphocytes via inhibition of cell proliferation and Interleukin-2 (IL-2)
      signalling. This latter effect of VacA is dependent on the beta2-integrin subunit
      CD18, acting as a receptor for intracellular uptake of VacA. In this study, we
      investigated the mechanism of endocytosis of VacA into primary human T
      lymphocytes. A screen with chemical inhibitors for different sets of kinases
      identified Ser/Thr kinases of the protein kinase C (PKC) family as crucial.
      Specific inhibitory peptides blocking PKCeta or PKCzeta-phosphorylating activity,
      but not PKCalpha/beta specific peptides, resulted in a strong reduction or
      complete block of VacA uptake. Thus the phosphorylating activity of PKCeta and
      PKCzeta is essential for the induction of VacA endocytosis. Furthermore,
      mimicking of a possible PKC-mediated threonine (T(758)) phosphorylation of the
      CD18 cytoplasmic tail in resting primary T cells induced VacA endocytosis via
      activation of the small GTPases Cdc42 and Rac-1. We conclude that VacA is
      endocytosed into primary T cells via a clathrin-independent pathway.

PMID- 21083637
TI  - Six years' experience with high-intensity focused ultrasonography for prostate
      cancer: oncological outcomes using the new 'Stuttgart' definition for biochemical
      failure.
AB  - OBJECTIVE: * To determine oncological outcomes after high-intensity focused
      ultrasonography (HIFU) treatment in patients with localized prostate cancer using
      a new, more accurate, definition ('Stuttgart' definition) of biochemical failure.
      PATIENTS AND METHODS: * We performed a retrospective review of all patients in
      our centre who received first-line treatment with a second-generation AblathermTM
      device (EDAP-TMS, Lyon, France). * Oncological failure was given either by
      biochemical failure (prostate-specific antigen, PSA, nadir plus 1.2 g/mL)
      (Stuttgart definition) or the start of salvage therapy because of a persistently
      positive biopsy after the HIFU procedure. * The 5-year biochemical-free survival
      rate and 5-year disease-free survival rate were calculated. RESULTS: * In total,
      53 patients were included (mean age, 72.5 +/- 4.5 years, range 60-79 years; 28
      low risk and 25 intermediate risk). None had undergone previous hormonal therapy.
      Mean +/-sd follow-up was 45.4 +/- 15.5 months (range 16-71 years). Mean (range)
      pre-treatment PSA was 8.5 +/- 4 (0.29-18) ng/mL. The median (range) PSA nadir
      value was 1 (0.01-14) ng/mL and occurred after a mean (range) of 5.09 (3-24)
      months. * Overall, 36 patients (67.9%) experienced oncological failure. * These
      included 33 cases (62.2%) of biochemical failure. A PSA nadir of <=0.2, 0.21-1.0
      and >1 ng/mL was reached in 20.8%, 30.2% and 49% of patients, respectively, and
      was associated with biochemical failure in 9.1%, 30.3% and 60.6%, respectively. *
      The 5-year biochemical-free survival rate and disease-free survival rate were
      21.7% and 13.5%, respectively. In multivariate analysis, a PSA nadir of >1 ng/mL
      was significantly associated with a risk of biochemical and oncological failure
      (P= 0.002 and P < 0.001). * Oncological failure was not associated with any risk
      group. * No patient died from prostate cancer. CONCLUSIONS: * In our experience,
      AblathermTM treatment for clinically localized prostate cancer was associated
      with a high rate of biochemical failure as determined by the 'Stuttgart'
      definition, and did not achieve effective cancer control. * The PSA nadir value
      after HIFU treatment was a significant predictor of treatment failure.

PMID- 21083638
TI  - Solitary, isolated metastatic disease to the kidney: Memorial Sloan-Kettering
      Cancer Center experience.
AB  - OBJECTIVE: * To analyse the clinical characteristics and outcomes of patients who
      underwent nephrectomy for solitary, isolated metastatic disease to the kidney.
      PATIENTS AND METHODS: * From July 1989 to July 2009, we identified 13 patients
      who underwent nephrectomy for solitary metastasis to the kidney. Patients'
      demographics, intra-operative variables and outcomes are reported. RESULTS: * The
      median age at nephrectomy was 52 years (range 33-79). Eleven patients (85%) had
      an incidentally discovered renal mass, whereas two patients (15%) presented with
      gross haematuria. * Median time from initial surgery at the primary site to
      development of metastatic disease to the kidney was 63 months (range 9-136). No
      patient had evidence of disease at other sites at the time of nephrectomy. In
      seven patients (54%), the kidney was the first site of recurrence. * The most
      common primary site was the lung in five patients (38%), followed by the colon in
      two (15%), chest wall in two (15%) and bone, brain, breast and salivary gland in
      one patient each (8%). * Of the 14 procedures performed, eight (57%) were partial
      nephrectomy (PN) and six (43%) were radical nephrectomy (RN). * Four patients
      died after progression from the primary tumour, all within 2 years of
      nephrectomy. One patient with a primary chondrosarcoma had no evidence of disease
      at last follow-up and died from other causes 50 months after nephrectomy. The
      median follow-up for the eight patients who were alive at last follow-up was 30
      months after nephrectomy. Four of these patients had no evidence of disease and
      four patients were alive with metastatic disease. CONCLUSION: * Kidney
      involvement by metastatic disease can occur as isolated solitary lesions. Some
      patients will also have the kidney as the first and only site of metastatic
      involvement. The presence of an isolated renal metastasis should not be
      considered an end-stage disease, and nephrectomy can be offered for highly
      selected patients as a therapeutic option.

PMID- 21083639
TI  - Volar onlay urethroplasty for reconstruction of female urethra in recurrent
      stricture disease.
AB  - OBJECTIVE: * To report our experience with a new and simple method of urethral
      repair with a volar onlay of free labium minus graft. Strictures of the female
      urethra are rare, and it is well accepted that the therapeutic options of
      dilation and urethrotomy are not lasting solutions as a result of their high
      recurrence rates. However, there is no consensus regarding the best way to
      reconstruct the female urethra in the case of stricture disease. PATIENTS AND
      METHODS: * Four consecutive female patients with a long lasting history of
      recurrent urethral strictures underwent open urethroplasty with a volar situated
      free split thickness epidermal graft from the labium minus. * The surgical
      technique is described and a short-term follow-up is presented. RESULTS: *
      Operating time was 40-140 min (mean 105 min), and the graft measured between 2 *
      1.5 cm and 3 * 2.5 cm. Follow-up time was 11-19 months. Maximum urinary flow rate
      could be improved from a baseline of 9.4-11.2 mL/s (preoperatively, after
      intermittent use of dilation) to 19-23 mL/s. * Postvoid residual urine volume was
      0-50 mL preoperatively and no postvoid residual urine volume postoperatively. *
      Urinary catheters were removed after 21 days. Urinary stress incontinence did not
      occur postoperatively. No complications related to the graft donor site were
      found. CONCLUSIONS: * The reported data concerning a new therapeutic approach for
      the treatment of recurrent female urethral stricture show that a volar onlay
      urethroplasty represents a feasible, safe and simple surgical method. * Larger
      series with long-term follow-up are needed for further evaluation.

PMID- 21083640
TI  - A multicentre, prospective, randomized trial: comparative efficacy of tamsulosin
      and nifedipine in medical expulsive therapy for distal ureteric stones with renal
      colic.
AB  - OBJECTIVE: * To determine the comparative efficacy of tamsulosin and nifedipine
      in medical expulsive therapy (MET) for distal ureteric stones with renal colic.
      PATIENTS AND METHODS: * We evaluated the comparative efficacy of tamsulosin and
      nifedipine in MET in a prospective randomized trial of 3189 outpatients from 10
      centres in China. * Eligible patients randomly received tamsulosin or nifedipine.
      Efficacies of the two agents in MET were compared at 4 weeks. * The primary
      endpoint was overall stone-expulsion rate. * Secondary endpoints were stone
      expulsion time, rate of pain relief therapy, mean analgesic consumption for renal
      colic recurrence, and side-effects incidence. RESULTS: * Stone-expulsion rates in
      the tamsulosin group (group 1) were greater than those in the nifedipine group
      (group 2; P < 0.01). * There was a significant variation in stone-expulsion rates
      and times between groups 1 and 2 (P < 0.01); with improvements in stone-expulsion
      rate and time significantly better in group 1 than in group 2. * There was a
      significant variation in the rate of pain relief therapy for renal colic
      recurrence between groups 1 and 2 (P < 0.01); patients in group 1 required
      significantly less analgesics than those in group 2 (P < 0.01). * There were no
      statistically significant differences in side-effects incidence between the
      groups. CONCLUSIONS: * Administration of tamsulosin and nifedipine in MET was
      determined to be safe and effective for distal ureteric stones with renal colic.
      * Tamsulosin was significantly better than nifedipine in relieving renal colic
      and facilitating ureteric stone expulsion.

PMID- 21083641
TI  - Twist1 and Y-box-binding protein-1 promote malignant potential in bladder cancer
      cells.
AB  - OBJECTIVE: To investigate the roles of Twist1 and Y-box binding protein-1 (YB-1)
      and their potential as therapeutic targets in bladder cancer (BC), as both have
      been suggested to play important roles in tumour growth, invasion and drug
      resistance. MATERIALS AND METHODS: Bladder cancer cell lines (TCCsup, UMUC3, T24
      and KK47 cells) were used. Twist1 and YB-1 expression levels were assessed by
      luciferase reporter assay, quantitative real-time polymerase chain reaction (PCR)
      and western blot analysis. Tumour growth and cell cycle were analysed by cell
      proliferation assay and flow cytometry, respectively. Invasive and motile
      abilities were investigated by scratch-wound test and migration assay,
      respectively. Cytotoxicity assay was performed to determine drug sensitivity.
      RESULTS: The findings showed that Twist1 regulated YB-1 expression in BC cells.
      Both Twist1 and YB-1 were involved in cell growth, invasion, motility and
      resistance to cisplatin and doxorubicin, but not to 5-fluorouracil (5-FU).
      CONCLUSION: The present study showed that Twist1 regulates YB-1 expression and
      that both Twist1 and YB-1 promote malignant potentials, including tumour growth,
      invasion and anti-cancer-drug resistance, indicating that both Twist1 and YB-1
      are novel molecular targets in BC.

PMID- 21083642
TI  - Prediction of outcomes after radical prostatectomy in patients diagnosed with
      prostate cancer of biopsy Gleason score >= 8 via contemporary multi (>= 12)-core
      prostate biopsy.
AB  - OBJECTIVE: * To investigate the outcome of patients who underwent radical
      prostatectomy (RP) for prostate cancer of biopsy Gleason score >= 8 diagnosed via
      contemporary prostate biopsy. PATIENTS AND METHODS: * We reviewed records of 151
      patients who underwent RP for prostate cancer of biopsy Gleason score >= 8
      detected via multi (>= 12)-core prostate biopsy without any neoadjuvant or
      adjuvant treatment. * Preoperative predictors of pathologically organ-confined
      disease along with biochemical recurrence-free survival were analyzed via
      multivariate logistic regression and Cox proportional hazards model. RESULTS: *
      For 151 total subjects, 5-year estimated biochemical recurrence-free survival
      rate was 41.0%. Patients with pathologically organ-confined disease were observed
      to have much higher 5-year biochemical recurrence-free survival rate than those
      otherwise (72.1 vs 31.5%, P < 0.001). * Serum PSA level (P= 0.031) and maximum
      tumour length in a biopsy core (P= 0.005) were observed to be significant
      preoperative predictors of having pathologically organ-confined disease. * As for
      biochemical recurrence-free survival following RP, serum PSA (P= 0.023), biopsy
      Gleason score (P= 0.032), and percent of total tumour length in biopsy cores (P <
      0.001) were observed be significant preoperative predictors on multivariate
      analysis. CONCLUSION: * Among contemporary patients with biopsy Gleason score >=
      8 who underwent RP alone, patients with pathologically organ-confined disease
      demonstrated significantly better biochemical outcome than others. Serum PSA
      level and maximum tumour length in a biopsy core, independent predictors of organ
      confined disease, would be useful in the selection of candidates for RP among
      patients presenting with biopsy Gleason score >= 8.

PMID- 21083643
TI  - Early prostate cancer--which treatment do men prefer and why?
AB  - STUDY TYPE: Preference (prospective cohort). LEVEL OF EVIDENCE: 1b. What's known
      on the subject? and What does the study add? In general the literature suggests
      that there is a need for improvement in aiding men diagnosed with early prostate
      cancer in their decision making about treatment options and that our
      understanding of this process is inadequate. There is limited data analyzing the
      reasons why these men decide between potentially curative or observational
      treatments and data evaluating patients' views before and after definitive
      therapy are scarce. This study begins the process of understanding the reasons
      underlying a patient's final treatment decision. Being a prospective study, it
      looks at the thought processes of these men before treatment during the time the
      decision is made. It also documents how satisfied patients are with their choice
      after their treatment and whether they would choose the same treatment again.
      OBJECTIVE: To identify the reasons for patients with localised prostate cancer
      choosing between treatments and the relationship of procedure type to patient
      satisfaction post-treatment. PATIENTS AND METHODS: 768 men with prostate cancer
      (stage T1/2, Gleason<=7, PSA<20 ug/L) chose between four treatments: radical
      prostatectomy, brachytherapy, conformal radiotherapy and active surveillance.
      Prior to choosing, patients were counselled by a urological surgeon, clinical
      (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons
      for choice were recorded. Post-treatment satisfaction was examined via postal
      questionnaire. RESULTS: Of the 768 patients, 305 (40%) chose surgery, 237 (31%)
      conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active
      surveillance. Sixty percent of men who opted for radical prostatectomy were
      motivated by the need for physical removal of the cancer. Conformal radiotherapy
      was mainly chosen by patients who feared other treatments (n=63, 27%). Most men
      chose brachytherapy because it was more convenient for their lifestyle (n=64,
      39%). Active surveillance was chosen by patients for more varied reasons. Post
      treatment satisfaction was assessed in a subgroup who took part in the QOL aspect
      of this study. Of the respondents to the questionnaire, 212(87.6%) stated that
      they were satisfied/extremely satisfied with their choice and 171(92.9%)
      indicated they would choose the same treatment again. CONCLUSION: Men with early
      prostate cancer have clear reasons for making decisions about treatment. Overall,
      patients were satisfied with the treatment and indicated that despite different
      reasons for choosing treatment, they would make the same choice again.

PMID- 21083644
TI  - Remote ischemic preconditioning prevents systemic platelet activation associated
      with ischemia-reperfusion injury in humans.

PMID- 21083647
TI  - Iloprost in dermatology.
AB  - Rheologically active pharmacotherapy is of high importance in many dermato
      logical diseases. The intravenous administration of iloprost belongs to the most
      effective systemic therapeutic agents that serve this pharmacodynamic approach
      and additionally substantial knowledge on the safety and efficacy exists. We
      review the dermatologically relevant data in order to offer an easy, thematically
      focused overview to practicing dermatologists.

PMID- 21083646
TI  - Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood.
AB  - BACKGROUND AND OBJECTIVES: Patients treated with percutaneous coronary
      intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce
      thrombotic complications. The choice of methodology for monitoring the effects of
      treatment and assessing its efficacy is still a topic of debate. We evaluated how
      decreased P2Y12 function influences platelet aggregate (thrombus) size measured
      ex vivo. METHODS AND RESULTS: We used confocal videomicroscopy to measure in real
      time the volume of platelet thrombi forming upon blood perfusion over fibrillar
      collagen type I at a wall shear rate of 1500 s(-1). The average volume was
      significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or
      ticlopidine (12) than in 21 controls, but individual values were above the lower
      limit of the normal distribution, albeit mostly within the lower quartile, in
      61.3% of cases. Disaggregation of platelet thrombi at later perfusion times
      occurred frequently in the patients. Vasodilator-stimulated phosphoprotein
      phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient
      group, and only 22.6% of individual values were above the lower normal limit. We
      found no correlation between volume of thrombus formed on collagen fibrils and
      level of P2Y12 inhibition, suggesting that additional and individually variable
      factors can influence the inhibitory effect of treatment on platelet function.
      CONCLUSIONS: Measurements of platelet thrombus formation in flowing blood
      reflects the consequences of antiplatelet therapy in a manner that is not
      proportional to P2Y12 inhibition. Combining the results of the two assays may
      improve the assessment of thrombotic risk.

PMID- 21083645
TI  - Clinical significance of a negative D-dimer level in patients with confirmed
      venous thromboembolism. Findings from the RIETE Registry.

PMID- 21083648
TI  - Treatment and side effect management of CTLA-4 antibody therapy in metastatic
      melanoma.
AB  - Immune-modifying monoclonal antibodies may induce or enhance the natural immune
      response against tumor cells. The complex interaction between antigen-presenting
      cells and T lymphocytes as an immune response is strongly affected by anti-CD152
      (CTLA-4)-antibodies. The cytotoxic T-lymphocyte (CTLA-4) receptor binds molecules
      of the B7-family which leads to a suppression of T cells. Specific CTLA-4
      antibodies induce an unrestrained T-cell activation. Treatment with the CTLA-4
      antibodies ipilimumab and tremelimumab has been investigated in metastatic
      melanoma only within clinical trials. Currently, the critical phase III trial on
      ipilimumab is in the final analysis process and expected to lead to approval.
      CTLA-4 antibodies belong to the most promising new molecules for the treatment of
      advanced melanoma. During treatment with CTLA-4 antibodies, distinct adverse
      events may occur. Treating physicians must be familiar with their appropriate
      treatment and prophylaxis. The most frequently observed side effects are diseases
      such as an autoimmune colitis which is typically characterized by a mild to
      moderate, but occasionally also severe and persistent diarrhea. Other autoimmune
      mediated side effects like hypophysitis, hepatitis, iridocyclitis or an
      exacerbation of lupus nephritis have been reported in the literature. Their early
      recognition and treatment are mandatory to reduce the risk of sequelae for CTLA-4
      antibod-treated patients. Autoimmune-mediated side effects are reported to
      correlate positively with treatment response. We review the mechanisms of action,
      provide an update on clinical trials with the two CTLA-4-antibodies for
      metastatic melanoma, and present detailed recommendations for managing the side
      effects of these new agents.

PMID- 21083649
TI  - In humans IL-6 is released from the brain during and after exercise and
      paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice.
AB  - AIM: Plasma interleukin-6 (IL-6) increases during exercise by release from active
      muscles and during prolonged exercise also from the brain. The IL-6 release from
      muscles continues into recovery and we tested whether the brain also releases IL
      6 in recovery from prolonged exercise in humans. Additionally, it was evaluated
      in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in
      the brain as modulated by brain glycogen levels. METHODS: Nine healthy male
      subjects completed 4 h of ergometer rowing while the arterio-jugular venous
      difference (a-v diff) for IL-6 was determined. The IL-6 mRNA and the glycogen
      content were determined in mouse hippocampus, cerebellum and cortex before and
      after 2 h treadmill running (N = 8). RESULTS: At rest, the IL-6 a-v diff was
      negligible but decreased to -2.2 +/- 1.9 pg ml(-1) at the end of exercise and
      remained low (-2.1 +/- 2.1 pg ml(-1) ) 1 h into the recovery (P < 0.05 vs. rest).
      IL-6 mRNA was expressed in the three parts of the brain with the lowest content
      in the hippocampus (P < 0.05) coupled to the highest glycogen content (3.2 +/-
      0.8 mmol kg(-1) ). Treadmill running increased the hippocampal IL-6 mRNA content
      2-3-fold (P < 0.05), while the hippocampal glycogen content decreased to 2.6 +/-
      0.6 mmol kg(-1) (P < 0.05) with no significant changes in the two other parts of
      the brain. CONCLUSION: Human brain releases IL-6 both during and in recovery from
      prolonged exercise and mouse data suggest that concurrent changes in IL-6 mRNA
      and glycogen levels make the hippocampus a likely source of the IL-6 release from
      the brain.

PMID- 21083650
TI  - An fMRI study of prefrontal dysfunction and symptomatic recovery in
      schizophrenia.
AB  - OBJECTIVE: Prefrontal cortical dysfunction has been implicated in the
      pathophysiology of schizophrenia but it is unclear to what extent these are
      related to changes in symptomatology as well as task demand. METHOD: We examined
      the neural correlates of symptom change and task demand during a longitudinal
      functional magnetic resonance imaging (fMRI) study using a verbal fluency task
      with differential task demands in patients with schizophrenia and matched healthy
      control subjects. The fMRI data were acquired using clustered acquisition
      technique, enabling ongoing monitoring of behavioural responses, in the patient
      group on two occasions separated by 6-8 weeks, and the control group at baseline.
      RESULTS: Positive psychotic symptoms were significantly reduced over the 6-8-week
      duration of the study. This change was associated with increased activation
      within the left middle frontal gyrus and decreased activation of the left
      precuneus. An interaction between symptom change and task demand was evident in
      the activation of the left middle frontal gyrus. The decrease in positive
      symptoms was associated with normalisation of activation in the dorsolateral
      prefrontal cortex and a decrease in parietal activation during the verbal fluency
      task. CONCLUSION: The data supports the role of dysfunctional prefronto-parietal
      relationships in the genesis of positive psychotic symptoms.

PMID- 21083651
TI  - Guidelines on travel-related venous thrombosis.
AB  - Long duration travel is a weak risk factor for the development of venous
      thromboembolism (VTE). The incidence of VTE after flights of >4 h is 1 in 4656
      and for flights of more than 8 h in low and intermediate risk flyers is around
      0.5%. Severe symptomatic pulmonary embolism in the period immediately after
      travel is extremely rare after flights of <8 h. In flights over 12 h the rate is
      5 per million. VTE may be attributable to travel if it occurs up to 8 weeks
      following the journey. The risk of travel-related thrombosis is higher in
      individuals with pre-existing risk factors for the development of VTE. There is
      no evidence for an association between dehydration and travel-associated VTE and
      so whilst maintaining good hydration is unlikely to be harmful it cannot be
      strongly recommended for prevention of thrombosis (recommendation grade 2, level
      of evidence, B). There is indirect evidence that maintaining mobility may prevent
      VTE and, in view of the likely pathogenesis of travel-related VTE, maintaining
      mobility is a reasonable precaution for all travellers on journeys over 3 h (2B).
      Global use of compression stockings and anticoagulants for long distance travel
      is not indicated (1C). Assessment of risk should be made on an individual basis
      but it is likely that recent major surgery (within 1 month), active malignancy,
      previous unprovoked VTE, previous travel-related VTE with no associated temporary
      risk factor or presence of more than one risk factor identifies those travellers
      at highest thrombosis risk (1C). Travellers at the highest risk of travel-related
      thrombosis undertaking journeys of >3 h should wear well fitted below knee
      compression hosiery (2B). Where pharmacological prophylaxis is considered
      appropriate, anticoagulants as opposed to anti-platelet drugs are recommended
      based on the observation that, in other clinical scenarios, they provide more
      effective thromboprophylaxis. Usual contraindications to any form of
      thromboprophylaxis need to be borne in mind (2C).

PMID- 21083653
TI  - Thalidomide after lenalidomide: a possible treatment regimen in relapse
      refractory multiple myeloma patients.

PMID- 21083652
TI  - Pathophysiology and management of chronic immune thrombocytopenia: focusing on
      what matters.
AB  - Immune thrombocytopenia (ITP) is a common autoimmune disease characterized by low
      platelet counts and an increased risk of bleeding. Antibody-mediated platelet
      destruction has been the prevailing hypothesis to explain ITP pathogenesis,
      supported by the efficacy of B-cell depletion therapy; however, the recent
      success of thrombopoietin receptor agonists lends support to the notion that
      platelet production is also insufficient. Best practice for the management of
      chronic ITP has not yet been established because data from comparative trials are
      lacking. Despite renewed interest in novel drugs capable of increasing platelet
      counts, ultimate treatment goals for ITP patients must be kept in mind: to
      improve patients' health and well-being. In this article, the pathophysiology of
      ITP is reviewed and key remaining questions about mechanism are explored. A
      rational approach to the management of ITP in adults is outlined, acknowledging
      evidence and evidence gaps, and highlighting the need for clinically important
      endpoints in future clinical trials.

PMID- 21083654
TI  - The role of BCL6 in lymphomas and routes to therapy.
AB  - BCL6 is a transcription factor that has essential B-cell and T-cell roles in
      normal antibody responses. It is involved in chromosomal translocations in
      diffuse large B-cell lymphoma (DBCL; including primary mediastinal B-cell
      lymphoma) and nodular lymphocyte predominant Hodgkin lymphoma, and is expressed
      in follicular lymphoma and Burkitt's lymphoma. The neoplastic T-cells of
      angioimmunoblastic T-cell lymphoma also express BCL6. BCL6 prevents terminal B
      cell differentiation largely through repression of PRDM1. In the "cell of origin"
      classification of DLBCL BCL6 is associated with the germinal centre subtype,
      which carries a good response to modern treatments. More recently, specific BCL6
      antagonists, including small molecule inhibitors, have been developed. These
      antagonists have demonstrated that DLBCL cells, in which BCL6 is
      transcriptionally active, are dependent on this gene for survival. BCL6
      antagonists are active against primary DLBCL and may find future application in
      the treatment of lymphomas.

PMID- 21083655
TI  - Mitoxantrone in combination with an inhibitor of DNA-dependent protein kinase: a
      potential therapy for high risk B-cell chronic lymphocytic leukaemia.
AB  - Defects in the DNA damage response pathway [e.g. del(17p)] are associated with
      drug-resistant B-cell chronic lymphocytic leukaemia (CLL). We previously
      demonstrated that over-expression of DNA-dependent protein kinase (DNA-PK)
      correlates with chemo-resistance and that inhibition of DNA-PK sensitizes CLL
      cells to chemotherapeutics. Here, we investigated expression of DNA-PK and other
      proteins that impact on drug resistance, and evaluated the effects of a DNA-PK
      inhibitor (NU7441) on mitoxantrone-induced cytotoxicity in CLL cells. NU7441
      sensitized cells from 42/49 CLL samples to mitoxantrone, with sensitization
      ranging from 2- to 200-fold Co-culture of CLL cells in conditioned stromal medium
      increased chemoresistance but did not reduce sensitization by NU7441.
      Mitoxantrone treatment induced gammaH2AX foci and NU7441 increased their
      longevity (24 h). NU7441 prevented mitoxantrone-induced autophosphorylation of
      the DNA-PK catalytic subunit (DNA-PKcs) at Ser 2056, confirming that DNA-PK
      participates in repair of mitoxantrone-induced DNA damage. del(17p) cases were
      more resistant to mitoxantrone than del(13q) cases, but were resensitized (7-16
      fold) by co-incubation with NU7441. Expression of DNA-PKcs, Ku80, P-glycoprotein
      and topoisomerase IIbeta were significantly higher in del(17p) cases. PRKDC mRNA
      levels correlated with DNA-PKcs protein expression, which predicted shorter
      survival. These data confirm the potential of DNA-PK as a therapeutic target in
      poor prognosis CLL.

PMID- 21083657
TI  - Clinical evaluation of the European LeukaemiaNet criteria for
      clinicohaematological response and resistance/intolerance to hydroxycarbamide in
      essential thrombocythaemia.
AB  - Standardized criteria of response to treatment and a unified definition of
      resistance/intolerance to hydroxycarbamide (HC) in essential thrombocythaemia
      (ET) have been proposed by the European LeukaemiaNet (ELN). We have
      retrospectively evaluated such criteria in 166 ET patients treated with HC for a
      median of 4.5 years. Overall, 134 patients achieved a complete
      clinicohaematological response (CR) and 25 a partial response. Thirty-three
      patients met at least one of the ELN criteria defining resistance (n = 15) or
      intolerance (n = 21) to HC. Fifteen cases developed anaemia with thrombocytosis,
      which was associated with a high incidence of myelofibrosis and death from any
      cause. Other definitions of resistance were less useful. Factors determining the
      thrombotic risk were a history of prior thrombosis and a baseline leucocyte count
      >10 * 109/ l. Of note, patients achieving a CR, even if sustained during the
      entire follow-up, did not benefit from a lower incidence of thrombosis or an
      improved survival. In conclusion, most ET patients respond to HC, but the
      achievement of response, as defined by the ELN, does not correlate with the
      patients' outcome. The best discriminating ELN criterion of resistance to HC was
      the detection of anaemia, which also identified a subgroup of patients with poor
      prognosis.

PMID- 21083656
TI  - Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALT): single
      institution experience in a large cohort of patients.
AB  - Extranodal marginal zone B-cell lymphoma is the most common orbital tumour. We
      conducted a retrospective analysis to examine: (i) the impact of initial
      presentation and staging on outcome and (ii) response to various treatment
      modalities and the effect of the latter on recurrence. Ninety patients with
      primary ocular adnexal marginal zone lymphoma (POAML) diagnosed at our
      institution between 1984 and 2009 were studied. POAML was associated with
      monoclonal gammopathy (13%) at presentation. Most POAML patients (86%) presented
      with Ann-Arbor stage I disease. Radiotherapy led to excellent local control, but
      relapses occurred in 18% of Ann-Arbor stage I patients during a median follow-up
      of 5 years. Local relapses, including secondary central nervous system (CNS)
      involvement, were observed in patients receiving radiation doses <30.6 Gy. No
      differences in relapse rate and survival were observed between patients who did
      or did not undergo staging bone marrow biopsy. Ann-Arbor stage II-IV disease and
      high lactate dehydrogenase levels were associated with shorter freedom from
      progression. In conclusion, POAML is an indolent lymphoma with continuous risk
      for relapse. Radiation doses of at least 30.6 Gy should be given in Ann-Arbor
      stage I disease, since lower doses may be more frequently associated with
      relapses, including CNS relapses.

PMID- 21083658
TI  - Intravascular inhibition of factor VIIa and the analogue NN1731 by antithrombin.
AB  - NN1731 is a recombinant activated factor VII (rFVIIa) analogue with increased
      intrinsic activity. This also applies to its reactivity towards antithrombin
      (AT), the role of which was investigated in a pharmacokinetic (PK) study. NN1731
      or rFVIIa was administered to normal and haemophilia A dogs and elimination was
      measured by FVIIa clot activity, FVIIa- and FVIIa-AT antigen. In vitro AT complex
      formation was studied in canine plasma spiked with NN1731 or rFVIIa. Based on
      FVIIa antigen concentrations, PK profiles in normal and haemophilia A dogs were
      similar for NN1731 and rFVIIa with antigen half lives, t(1/2) ~1.8 h. In
      contrast, PK profiles based on activity measurements were distinctly different.
      NN1731 induced a strong, short lasting (t(1/2) ~0.5 h) pro-coagulant response,
      whereas rFVIIa induced a lower, longer lasting (t(1/2) ~1.1 h) response. Western
      Blot and FVIIa-AT antigen analysis demonstrated in vivo AT complex formation that
      accounted for these divergences. AT complex formation with FVIIa or NN1731 in
      vitro in canine plasma was considerably slower than the in vivo reaction. The
      results suggest that in vivo inhibition by AT contributes significantly to define
      drug duration in haemophilia treatment with rFVIIa and in particular with the
      NN1731 analogue.

PMID- 21083659
TI  - X-linked lymphoproliferative syndrome: a genetic condition typified by the triad
      of infection, immunodeficiency and lymphoma.
AB  - X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency
      characterized by the clinical triad of increased susceptibility to primary
      Epstein-Barr virus (EBV) infection, dysgammaglobulinaemia and lymphoma. Most
      cases are caused by germline mutations in the SH2D1A gene, which encodes the
      adaptor molecule Signalling Lymphocytic Activation Molecule (SLAM)-associated
      protein (SAP). Recently, a subset of patients with an XLP-like phenotype was
      found to carry mutations in XIAP, the gene encoding the X-linked inhibitor of
      apoptosis protein (XIAP). Studies of XLP patients and Sap-/- mice reveal that
      loss of SAP expression impairs immune cell activities, such as natural killer and
      CD8+ T cell cytotoxicity, T cell cytokine production, activation-induced cell
      death, germinal centre formation and natural killer T cell development. Efforts
      to dissect the diverse roles of SAP and XIAP are enhancing our understanding of
      immune cell biology and defining how genetic defects in these molecules
      predispose to EBV-specific as well as more general cellular and humoral immune
      dysfunction. These studies are also highlighting critical signalling pathways
      that might be amenable to pharmacological targeting to improve the treatment of
      XLP and other disorders associated with impaired antiviral and antitumour
      immunity.

PMID- 21083660
TI  - Guidelines on the use of irradiated blood components prepared by the British
      Committee for Standards in Haematology blood transfusion task force.

PMID- 21083661
TI  - Origin and evolution of the dependent lineages in the genetic caste determination
      system of Pogonomyrmex ants.
AB  - Hybridizing harvester ants of the Pogonomyrmex barbatus/rugosus complex have an
      exceptional genetic caste determination (GCD) mechanism. We combined computer
      simulations, population genomics, and linkage mapping using >1000 nuclear AFLP
      markers and a partial mtDNA sequence to explore the genetic architecture and
      origin of the dependent lineages. Our samples included two pairs of hybridizing
      lineages, and the mitochondrial and nuclear data showed contradicting affinities
      between them. Clustering of individual genotypes based on nuclear markers
      indicated some exceptions to the general GCD system, that is, interlineage hybrid
      genes as well as some pure-line workers. A genetic linkage map of P. rugosus
      showed one of the highest recombination rates ever measured in insects (14.0
      cM/Mb), supporting the view that social insects are characterized by high
      recombination rates. The population data had 165 markers in which sibling pairs
      showed a significant genetic difference depending on the caste. The differences
      were scattered in the genome; 13 linkage groups had loci with F(ST)>0.9 between
      the hybridizing lineages J1 and J2.The mapping results and the population data
      indicate that the dependent lineages have been initially formed through
      hybridization at different points in time but the role of introgression has been
      insignificant in their later evolution.

PMID- 21083663
TI  - Inhibition of spontaneous network activity in neonatal hippocampal slices by
      energy substrates is not correlated with intracellular acidification.
AB  - Several energy substrates complementary to glucose, including lactate, pyruvate
      and beta-hydroxybutyrate, serve as a fuel for neurons. It was reported recently
      that these substrates can substantially modulate cortical excitability in
      neonatal slices. However, complementary energy substrates (CES) can also induce
      an intracellular acidification when added exogenously. Therefore, action of CES
      on the neuronal properties governing excitability in neonatal brain slices may be
      underlain by a change in the cell energy status or by intracellular
      acidification, or both. Here, we attempt to elucidate these possibilities in
      neonatal hippocampus by recording neuronal population activity and monitoring
      intracellular pH. We show that a spontaneous network activity pattern, giant
      depolarizing potentials (GDPs), characteristic for the neonatal hippocampal
      slices exposed to artificial cerebrospinal fluid, is strongly inhibited by CES
      and this effect is unlikely to be caused by a subtle intracellular acidification
      induced by these compounds. Indeed, a much stronger intracellular acidification
      in the HCO(3) -free solution inhibited neither the GDP frequency nor the GDP
      amplitude. Therefore, modulation of neuronal energy homeostasis is the most
      likely factor underlying the effect of lactate, pyruvate and beta-hydroxybutyrate
      on network excitability in neonatal brain slices.

PMID- 21083664
TI  - Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part
      III. cefquinome.
AB  - Cefquinome concentrations, following intravenous and aerosol administration to
      horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to
      plasma concentrations. Single dose of cefquinome sulphate (1 mg/kg) was
      administered intravenously to six horses followed by a single aerosol
      administration (225 mg) with a wash-out period of 14 days between treatments.
      After each drug administration, cefquinome concentrations in plasma and PELF,
      obtained by intrabronchial cotton swabs, were determined. After intravenous
      administration, cefquinome concentrations in plasma declined fast and were not
      detectable after 12 h. After aerosol administration, plasma concentrations were
      low or below limit of quantification (LOQ) during the entire sampling period. The
      degree of penetration of cefquinome into PELF after intravenous administration as
      described by the AUC(PELF) /AUC(plasma) ratio was 0.33. Following aerosol
      administration, cefquinome concentrations in PELF were high, but only detectable
      for 4 h. Based on AUC values, total cefquinome concentrations in PELF were one
      third of total plasma concentrations after intravenous administration together
      with shorter time above Minimum Inhibitory Concentrations (T > MIC) in PELF, thus
      twice daily dosing may be required when treating lower airway infections in
      horses. Lower doses of cefquinome can be administered as aerosols providing high
      local drug concentrations in lung, but additional optimization of formulation is
      needed to improve distribution and persistence in lung.

PMID- 21083662
TI  - Life-history QTLS and natural selection on flowering time in Boechera stricta, a
      perennial relative of Arabidopsis.
AB  - Plants must precisely time flowering to capitalize on favorable conditions.
      Although we know a great deal about the genetic basis of flowering phenology in
      model species under controlled conditions, the genetic architecture of this
      ecologically important trait is poorly understood in nonmodel organisms. Here, we
      evaluated the transition from vegetative growth to flowering in Boechera stricta,
      a perennial relative of Arabidopsis thaliana. We examined flowering time QTLs
      using 7920 recombinant inbred individuals, across seven laboratory and field
      environments differing in vernalization, temperature, and photoperiod. Genetic
      and environmental factors strongly influenced the transition to reproduction. We
      found directional selection for earlier flowering in the field. In the growth
      chamber experiment, longer winters accelerated flowering, whereas elevated
      ambient temperatures delayed flowering. Our analyses identified one large effect
      QTL (nFT), which influenced flowering time in the laboratory and the probability
      of flowering in the field. In Montana, homozygotes for the native allele at nFT
      showed a selective advantage of 6.6%. Nevertheless, we found relatively low
      correlations between flowering times in the field and the growth chambers.
      Additionally, we detected flowering-related QTLs in the field that were absent
      across the full range of laboratory conditions, thus emphasizing the need to
      conduct experiments in natural environments.

PMID- 21083665
TI  - Patient variation in veterinary medicine--part II--influence of physiological
      variables.
AB  - In veterinary medicine, the characterization of a drug's pharmacokinetic
      properties is generally based upon data that are derived from studies that employ
      small groups of young healthy animals, often of a single breed. In Part I of the
      series, we focused on the potential influence of disease processes, stress,
      pregnancy and lactation on drug pharmacokinetics. In this Part II of the series,
      we consider other covariates, such as gender, heritable traits, age, body
      composition, and circadian rhythms. The impact of these factors with respect to
      predicting the relationship between dose and drug exposure characteristics within
      an animal population is illustrated through the use of Monte Carlo simulations.
      Ultimately, an appreciation of these potential influences will improve the
      prediction of situations when dose adjustments may be appropriate.

PMID- 21083666
TI  - Pharmacokinetics of ceftiofur sodium and ceftiofur crystalline free acid in
      neonatal foals.
AB  - Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy
      against microorganisms isolated from septicemic neonatal foals. This
      pharmacokinetic study evaluated the intravenous and subcutaneous administration
      of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous
      administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6)
      in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite
      concentrations were measured using high performance liquid chromatography
      following drug administration. Mean (+/-SD) noncompartmental pharmacokinetic
      parameters for i.v. and s.c. ceftiofur sodium were: AUC(0->?) (86.4 +/- 8.5 and
      91 +/- 22 h.MUg/mL for i.v. and s.c., respectively), terminal elimination half
      life (5.82 +/- 1.00 and 5.55 +/- 0.81 h for i.v. and s.c., respectively),
      C(max(obs)) (13 +/- 1.9 MUg/mL s.c.), T(max(obs)) (0.75 +/- 0.4 h for s.c.). Mean
      (+/- SD) noncompartmental pharmacokinetic parameters for s.c. ceftiofur
      crystalline free acid were: AUC(0->?) (139.53 +/- 22.63 h.MUg/mL), terminal
      elimination half-life (39.7 +/- 14.7), C(max(obs)) (2.52 +/- 0.35 MUg/mL) and
      t(max(obs)) (11.33 +/- 1.63 h). No adverse effects attributed to drug
      administration were observed in any foal. Ceftiofur- and desfuroylceftiofur
      related metabolites reached sufficient plasma concentrations to effectively treat
      common bacterial pathogens isolated from septicemic foals.

PMID- 21083667
TI  - Haplotype-based study of the association of alcohol-metabolizing genes with
      alcohol dependence in four independent populations.
AB  - BACKGROUND: Ethanol is metabolized by 2 rate-limiting reactions: alcohol
      dehydrogenases (ADH) convert ethanol to acetaldehyde that is subsequently
      metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of
      East Asians have genetic variants that significantly impair this pathway and
      influence alcohol dependence (AD) vulnerability. We investigated whether
      variation in alcohol metabolism genes might alter the AD risk in four non-East
      Asian populations by performing systematic haplotype association analyses to
      maximize the chances of capturing functional variation. METHODS: Haplotype
      tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes
      were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the
      two ALDH genes in four diverse samples that included cases (lifetime AD) and
      controls (no Axis 1 disorders). The case control sample sizes were the following:
      Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American
      Indians: 226, 110; and Southwestern American (SW) Indians: 317, 72. RESULTS: In
      all four populations, as well as HapMap populations, 5 haplotype blocks were
      identified across the ADH gene cluster: (i) ADH5-ADH4; (ii) ADH6-ADH1A-ADH1B;
      (iii) ADH1C; (iv) intergenic; (v) ADH7. The ALDH1A1 gene was defined by 4 blocks
      and ALDH2 by 1 block. No haplotype or SNP association results were significant
      after correction for multiple comparisons; however, several results, particularly
      for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1
      and 2 (extending from intron 5 to the 3' UTR) yin yang haplotype (haplotypes that
      have opposite allelic configuration) association with AD in the Finns driven by
      SNPs rs3764435 and rs2303317, respectively, and an ALDH1A1 block 3 (including the
      promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs,
      all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains
      Indians. CONCLUSIONS: The systematic evaluation of alcohol-metabolizing genes in
      four non-East Asian populations has shown only modest associations with AD,
      largely for ALDH1A1 and ADH4. A concentration of signals for AD with ALDH1A1 yin
      yang haplotypes in several populations warrants further study.

PMID- 21083668
TI  - Child physical and sexual abuse: a comprehensive look at alcohol consumption
      patterns, consequences, and dependence from the National Alcohol Survey.
AB  - BACKGROUND: Previous research has documented a relationship between child sexual
      abuse and alcohol dependence. This paper extends that work by providing a
      comprehensive description of past year and lifetime alcohol consumption patterns,
      consequences, and dependence among women reporting either physical and sexual
      abuse in a national sample. METHODS: This study used survey data from 3,680 women
      who participated in the 2005 U.S. National Alcohol Survey. Information on
      physical and sexual child abuse and its characteristics were assessed in relation
      to 8 past year and lifetime alcohol consumption measures. RESULTS: Child physical
      or sexual abuse was significantly associated with past year and lifetime alcohol
      consumption measures. In multivariate analyses, controlling for age, marital
      status, employment status, education, ethnicity, and parental alcoholism or
      problem drinking, women reporting child sexual abuse vs. no abuse were more
      likely to report past year heavy episodic drinking (OR(adj) = 1.7; 95% CI 1.0 to
      2.9), alcohol dependence (OR(adj) = 7.2; 95% CI 3.2 to 16.5), and alcohol
      consequences (OR(adj) = 3.6; 95% CI 1.8 to 7.3). Sexual abuse (vs. no abuse) was
      associated with a greater number of past year drinks (124 vs. 74 drinks,
      respectively, p = 0.002). Sexual child abuse was also associated with lifetime
      alcohol-related consequences (OR(adj) = 3.5; 95% CI 2.6 to 4.8) and dependence
      (OR(adj) = 3.7; 95% CI 2.6 to 5.3). Physical child abuse was associated with 4 of
      8 alcohol measures in multivariate models. Both physical and sexual child abuse
      were associated with getting into fights, health, legal, work, and family alcohol
      related consequences. Alcohol-related consequences and dependence were more
      common for women reporting sexual abuse compared to physical abuse, 2 or more
      physical abuse perpetrators, nonparental and nonfamily physical abuse
      perpetrators, and women reporting injury related to the abuse. CONCLUSION: Both
      child physical and sexual abuse were associated with many alcohol outcomes in
      adult women, even when controlling for parental alcohol problems. The study
      results point to the need to screen for and treat underlying issues related to
      child abuse, particularly in an alcohol treatment setting.

PMID- 21083672
TI  - Risk factors for impaired health-related quality of life in functional dyspepsia.
AB  - BACKGROUND: The influence of patient characteristics on HRQoL in functional
      dyspepsia is poorly understood. AIM: To determine the contribution of gastric
      sensorimotor function, psychosocial factors & 'somatization' to HRQoL in
      functional dyspepsia. METHODS: In 259 tertiary care functional dyspepsia
      patients, we studied gastric sensorimotor function with barostat. We measured
      psychosocial factors and 'somatization' using self-report questionnaires. HRQoL
      was assessed using the SF-36 physical and mental composite scores (PCS, MCS).
      Bivariate associations between gastric sensorimotor function, psychosocial
      factors and 'somatization' on the one hand and PCS and MCS on the other were
      estimated. Variables significantly associated with PCS or MCS in bivariate
      analysis were entered into hierarchical multiple linear regression models.
      RESULTS: Mean PCS was 40.1 +/- 9.5; mean MCS was 45.1 +/- 10.8. 'Somatization' (P
      < 0.0001) and chronic fatigue (P = 0.002) were significantly associated with
      impaired PCS (R2 = 0.52, P < 0.0001). The effects of abuse history and depression
      were 'mediated' by 'somatization'. Trait anxiety (P = 0.02), alexithymia (P =
      0.06), depression (P = 0.06), positive affect (P < 0.0001), negative affect (P =
      0.002) and generalised anxiety disorder (P = 0.01) were significantly associated
      with impaired MCS (R2 = 0.67, P < 0.0001). CONCLUSIONS: 'Somatization' is the
      most important risk factor for impaired physical HRQoL in functional dyspepsia;
      it 'mediates' the effect of abuse history and depression. Mental HRQoL is mainly
      explained by psychosocial factors.

PMID- 21083669
TI  - Drinking motives in female smokers: factor structure, alcohol dependence, and
      genetic influences.
AB  - BACKGROUND: Alcohol and tobacco use often co-occur. Human and animal studies
      indicate that nicotine increases alcohol's rewarding effects and the motivation
      to consume it. The aims of this study were to examine whether the factorial
      architecture of self-reported motivations to consume alcohol differed between
      regular and nonregular cigarette smokers while taking into account the lifetime
      history of alcohol dependence and psychopathology, and to estimate the genetic
      and environmental influences on the motivations. METHODS: Using data on 2,189
      monozygotic and dizygotic female twins, we examined the factorial structure (item
      thresholds and factor loadings, means, and variances) of the items from the
      Drinking Motives Questionnaire (DMQ) in regular and nonregular smokers. Post hoc
      tests examined the association between the latent drinking motives factors and
      alcohol dependence in both groups. Twin models were fitted to the latent drinking
      motives factors, testing for variations in the magnitude of additive genetic,
      shared, and nonshared environmental influences between the groups. RESULTS: The 4
      DMQ factors (social, conformity, coping, and enhancement) were recovered in both
      groups, and their measurement structure was consistent across the groups. Regular
      smokers reported higher levels of coping, enhancement, and social motives while
      nonregular smokers reported higher conformity motives. Alcohol dependence was
      associated with higher scores on all motives in both groups; however, in a
      regression analysis that included all of the motives as predictor variables, only
      coping was significantly related to alcohol dependence. While twin models
      revealed evidence for substantially greater genetic influences on enhancement (h2
      = 0.40), coping (h2 = 0.35) and social (h2 = 0.37) drinking motives in regular
      compared to nonregular smokers, the power to statistically distinguish the 2
      groups was low. CONCLUSIONS: While the measurement structure of the drinking
      motive factors appears to be similar across regular and nonregular smokers,
      regular smokers report more motivation to drink for internal affect-related
      reasons and to obtain social reward. Of all the motives, coping was the most
      robust predictor of alcohol dependence in both the regular and the nonregular
      smokers. Further, genetic influences might play a larger role in drinking motives
      among regular smokers, which provides tentative evidence for latent genetic *
      smoking status interactions.

PMID- 21083671
TI  - Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease -
      subgroup results from a placebo-controlled study.
AB  - BACKGROUND: Treatment options for fistulizing Crohn's disease (CD) are limited.
      AIM: To examine whether fistula closure is maintained at week 26 following
      treatment with certolizumab pegol. METHODS: Patients with draining fistulas at
      baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab
      pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as >=100-point
      decrease from baseline in the Crohn's Disease Activity Index. Nonresponders
      (50/108) were excluded. At week 6, responders with draining fistulas (N = 58)
      were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4
      weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with
      a final assessment at week 26. RESULTS: The majority of patients (55/58) had
      perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had
      100% fistula closure compared with 17% of patients receiving placebo (P = 0.038).
      Protocol-defined fistula closure (>=50% closure at two consecutive post-baseline
      visits >=3 weeks apart) was not statistically significant (P = 0.069) with 54%
      and 43% of patients treated with certolizumab pegol and placebo achieving this
      end point, respectively. CONCLUSION: Continuous treatment with certolizumab pegol
      improves the likelihood of sustained perianal fistula closure compared with
      placebo.

PMID- 21083670
TI  - Limited associations of dopamine system genes with alcohol dependence and related
      traits in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD).
AB  - BACKGROUND: Over 50 years of evidence from research has established that the
      central dopaminergic reward pathway is likely involved in alcohol dependence
      (AD). Additional evidence supports a role for dopamine (DA) in other
      disinhibitory psychopathology, which is often comorbid with AD. Family and twin
      studies demonstrate that a common genetic component accounts for most of the
      genetic variance in these traits. Thus, DA-related genes represent putative
      candidates for the genetic risk that underlies not only AD but also behavioral
      disinhibition. Many linkage and association studies have examined these
      relationships with inconsistent results, possibly because of low power, poor
      marker coverage, and/or an inappropriate correction for multiple testing.
      METHODS: We conducted an association study on the products encoded by 10 DA
      related genes (DRD1-D5, SLC18A2, SLC6A3, DDC, TH, COMT) using a large, ethnically
      homogeneous sample with severe AD (n = 545) and screened controls (n = 509). We
      collected genotypes from linkage disequilibrium (LD)-tagging single nucleotide
      polymorphisms (SNPs) and employed a gene-based method of correction. We tested
      for association with AD diagnosis in cases and controls and with a variety of
      alcohol-related traits (including age-at-onset, initial sensitivity, tolerance,
      maximum daily drinks, and a withdrawal factor score), disinhibitory symptoms, and
      a disinhibitory factor score in cases only. A total of 135 SNPs were genotyped
      using the Illumina GoldenGate and Taqman Assays-on-Demand protocols. RESULTS: Of
      the 101 SNPs entered into standard analysis, 6 independent SNPs from 5 DA genes
      were associated with AD or a quantitative alcohol-related trait. Two SNPs across
      2 genes were associated with a disinhibitory symptom count, while 1 SNP in DRD5
      was positive for association with the general disinhibitory factor score.
      CONCLUSIONS: Our study provides evidence of modest associations between a small
      number of DA-related genes and AD as well as a range of alcohol-related traits
      and measures of behavioral disinhibition. While we did conduct gene-based
      correction for multiple testing, we did not correct for multiple traits because
      the traits are correlated. However, false-positive findings remain possible, so
      our results must be interpreted with caution.

PMID- 21083673
TI  - Randomised clinical trial: high-dose acid suppression for chronic cough - a
      double-blind, placebo-controlled study.
AB  - BACKGROUND: Cough may be a manifestation of gastro-oesophageal reflux disease
      (GERD). The utility of acid suppression in GERD-related cough is uncertain. AIM:
      To assess the impact of high-dose acid suppression with proton pump inhibitors
      (PPI) on chronic cough in subjects with rare or no heartburn. METHODS: Subjects
      were nonsmokers without history of asthma, with chronic cough for >8 weeks. All
      subjects underwent a baseline 24-h pH/impedance study, methacholine challenge
      test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole
      twice daily or placebo for 12 weeks. The primary outcome measure was the Cough
      Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response
      on Fisman Cough Severity/Frequency scores and change in laryngeal findings.
      RESULTS: Forty subjects were randomised (22 PPI, 18 placebo) and completed the
      study. There was no difference between PPI and placebo in CQLQ (mean improvement
      9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores.
      Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18)
      and 31.8% (seven of 22) in the placebo and PPI groups respectively. CONCLUSION:
      In subjects with chronic cough and rare or no heartburn, high-dose proton pump
      inhibitor does not improve cough-related quality of life or symptoms.

PMID- 21083674
TI  - Pilot study: fenofibrate for patients with primary biliary cirrhosis and an
      incomplete response to ursodeoxycholic acid.
AB  - BACKGROUND: Newer therapies are needed for patients with primary biliary
      cirrhosis and incomplete response to ursodeoxycholic acid (UDCA). Fenofibrate is
      a fibric acid postulated to regulate immune response and cell proliferation. AIM:
      To evaluate the efficacy and safety of fenofibrate in patients with primary
      biliary cirrhosis and incomplete response to UDCA. METHODS: We undertook a pilot
      study involving 20 patients with primary biliary cirrhosis and serum alkaline
      phosphatase (ALP) >= 2* ULN. Nonparametric statistical tests and Spearman
      correlation test were used as appropriate. RESULTS: Twenty patients received
      fenofibrate (160 mg/day) in addition to UDCA for 48 weeks. Median serum ALP
      decreased significantly at 48 weeks compared with baseline values [351 (214-779)
      U/L at baseline vs. 177 (60-384) U/L at 48 weeks, P < 0.05]. A rebound in ALP
      occurred upon drug discontinuation. Serum aspartate aminotransferase and
      Immunoglobulin M also decreased significantly, while bilirubin and albumin
      remained unchanged. Median IL-1 decreased from 28.9 (2.7-10 000) to 11.3 (2.5
      277.7) pg/mL (P = 0.049), and median IL-6 from 4.6 (3.2-5205) to 3.5 (3.2-73.4)
      pg/mL (P = 0.027). Heartburn was the most frequent adverse event, leading to
      discontinuation of two study subjects. CONCLUSIONS: Combination therapy of
      fenofibrate and UDCA induced significant biochemical improvement in patients with
      primary biliary cirrhosis and incomplete response to UDCA. Further studies are
      warranted.

PMID- 21083675
TI  - Dark green discoloration of the urine after prolonged propofol infusion: a case
      report.
AB  - WHAT IS KNOWN AND OBJECTIVE: Propofol, a commonly used sedative, has on rare
      occasions, been reported to discolour urine green. However, in previous reports,
      it is uncertain that whether this colour change is dose dependent. We report on a
      patient who produced dark green discoloration of urine from prolonged propofol
      infusion, administered for intractable epilepsy. CASE SUMMARY: The colour
      intensity of the patient's urine was dependent on propofol infusion rate.
      Reducing propofol infusion rate lightened the colour of the urine, eventually
      back to normal. WHAT IS NEW AND CONCLUSION: Green discoloration of the urine from
      propofol infusion is dose dependent. It is usually benign and reversible, as was
      the case for our patient.

PMID- 21083676
TI  - The amount counts: distinguishing neutrophil-mediated and lymphocyte-mediated
      cicatricial alopecia by compound follicles.

PMID- 21083678
TI  - What would Webster do?

PMID- 21083681
TI  - Indolent CD8+ lymphoid proliferation of the ear: report of two cases and review
      of the literature.
AB  - Indolent CD8+ lymphoid proliferation of the ear is a recently described cutaneous
      lymphoid proliferation that clinically presents with slow growing lesion(s) on
      the ear(s). In cases reported to date, there has been indolent clinical behavior
      and no evidence of systemic involvement. Characteristic histopathologic features
      include a non-epidermotropic diffuse dermal infiltrate of CD8+ T-lymphocytes with
      a lymphoblast-like appearance. T-cell clonality has also been observed. Herein,
      we present two patients who show clinical, histopathologic and immunophenotypic
      features similar to the original index cases described by Petrella et al. In
      addition, we review the literature regarding this unusual lymphoid proliferation
      and provide evidence that this entity represents a phenotypic variant of primary
      cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a concept proposed
      by Beltraminelli et al. in 2009. Differentiation between this lymphoproliferative
      process and other more aggressive CD8+ lymphomas is essential in avoiding
      excessive treatment of a condition that combines worrisome histopathology with
      indolent clinical behavior.

PMID- 21083682
TI  - Sleep problems and temperament in adolescents.
AB  - The aim of this study was to determine the association between temperament and
      sleep in adolescents. Participants included 516 adolescents and their mothers
      drawn from the community. Findings indicated that as with younger children, sleep
      and dimensions of temperament (sociability, impulsivity and negative affect) are
      related in adolescents.

PMID- 21083683
TI  - Management of problems related to the new morbidity by community-based
      paediatricians in Israel.
AB  - OBJECTIVES: To assess community-based paediatricians' management of clinical
      situations, particularly those related to the new morbidity (NM), such as chronic
      disease, developmental, behavioural, and psychosocial problems, and to identify
      the main associated factors. METHODS: The study population included all community
      based paediatricians employed by Israel's two largest health maintenance
      organizations in the central and southern regions of the country (n= 574; 74%
      response rate). Using a self-administered questionnaire including 20 vignettes
      describing common clinical situations (14 related to NM; 6 related to classic
      paediatrics (CP)), physicians reported how they would manage each situation and
      how they perceived their role in managing such problems. RESULTS: Paediatricians
      were less likely to take an active role in managing NM-related problems than CP
      related problems (68.3% vs. 93.2%; P < 0.001). In most NM situations, when
      paediatricians regarded the problem as part of their role, they were more likely
      to either manage the problem by themselves or with the help of other
      professionals. A multivariable linear regression model, adjusting for
      demographic, practice and training characteristics indicated the following
      predictive factors for taking an active role in managing NM (P < 0.001):
      practicing in the periphery, consulting with non-medical community-based
      professionals and combining community and hospital practice. CONCLUSIONS: To
      assure comprehensive paediatric care, simultaneous modification of
      paediatricians' residency training, practice environment and role perception are
      required.

PMID- 21083684
TI  - Are family-centred principles, functional goal setting and transition planning
      evident in therapy services for children with cerebral palsy?
AB  - BACKGROUND: Family-centred service, functional goal setting and co-ordination of
      a child's move between programmes are important concepts of rehabilitation
      services for children with cerebral palsy identified in the literature. We
      examined whether these three concepts could be objectively identified in
      programmes providing services to children with cerebral palsy in Alberta, Canada.
      METHODS: Programme managers (n= 37) and occupational and physical therapists (n=
      54) representing 59 programmes participated in individual 1-h semi-structured
      interviews. Thirty-nine parents participated in eleven focus groups or two
      individual interviews. Evidence of family-centred values in mission statements
      and advisory boards was evaluated. Therapists were asked to identify three
      concepts of family-centred service and to complete the Measures of Process of
      Care for Service Providers. Therapists also identified therapy goals for children
      based on clinical case scenarios. The goals were coded using the components of
      the International Classification of Functioning Disability and Health. Programme
      managers and therapists discussed the processes in their programmes for goal
      setting and for preparing children and their families for their transition to
      other programmes. Parents reflected on their experiences with their child's
      rehabilitation related to family-centredness, goal setting and co-ordination
      between programmes. RESULTS: All respondents expressed commitment to the three
      concepts, but objective indicators of family-centred processes were lacking in
      many programmes. In most programmes, the processes to implement the three
      concepts were informal rather than standardized. Both families and therapists
      reported limited access to general information regarding community supports.
      CONCLUSION: Lack of formal processes for delivery of family-centred service, goal
      setting and co-ordination between children's programmes may result in inequitable
      opportunities for families to participate in their children's rehabilitation
      despite attending the same programme. Standardized programme processes and
      policies may provide a starting point to ensure that all families have equitable
      opportunities to participate in their child's rehabilitation programme.

PMID- 21083685
TI  - Promoting secure attachment: evaluation of the effectiveness of an early
      intervention pilot programme with mother-infant dyads in Santiago, Chile.
AB  - BACKGROUND: Research indicates that the early attachment patterns of babies could
      influence their socio-emotional development and prevent the emergence of
      problematic behaviours in the child later in life. Many studies in the field of
      early attachment interventions have promoted a secure attachment bond between
      mother and infant. The purpose of this study was to evaluate the effectiveness of
      an early pilot intervention programme designed to promote a secure attachment
      bond in mother-infant dyads belonging to a population seeking regular treatment
      at urban health centres in Santiago, Chile. METHODS: Primipara mothers were
      randomly assigned to two intervention conditions: a secure attachment promotion
      programme (experimental group = 43) or an educational talk (control group = 29).
      The Strange Situation Assessment was used to collect data on the attachment
      patterns of babies. RESULTS: The results show that after the intervention, there
      were more babies with secure attachment in the experimental group than in the
      control group. CONCLUSIONS: These findings represent a preliminary step towards
      evaluating interventions aimed at promoting secure attachment in Chilean mother
      child dyads. While the effect of the intervention is not significant, the effect
      size obtained is respectable and consistent with other meta-analytic findings.

PMID- 21083686
TI  - Parent stress and child behaviour among young children with type 1 diabetes.
AB  - BACKGROUND: Parents of young children with type 1 diabetes (T1D) are responsible
      for executing a complex daily management regimen and are at risk for elevated
      levels of stress. Normative misbehaviour during the preschool years can
      complicate T1D management, and interpretation of behavioural concerns may vary
      because of child health status and parent stress. Within a paediatric
      transactional model framework, child characteristics (e.g. behaviour problems,
      metabolic control) and parent functioning (e.g. parenting stress, anxiety) likely
      impact one another. METHODS: Parents of 2- to 6-year-old children with T1D
      completed self-report measures, including the Pediatric Inventory for Parents
      (PIP), State-Trait Anxiety Inventory (STAI), Eyberg Child Behavior Inventory
      (ECBI), and 24-h Recall Interviews. Medical data were obtained by parent report
      and medical record review. It was hypothesized that greater parent stress and
      child blood glucose variability would be significantly associated with greater
      parent-reported child behaviour concerns. RESULTS: Moderate levels of parent
      stress and child behaviour problems were endorsed; however, parents perceived
      children's misbehaviour as problematic, particularly with relation to tasks
      relevant to diabetes management (e.g. bedtimes and mealtimes). Structural
      equation modelling indicated that greater general anxiety and paediatric
      parenting stress was associated with parent report of more problematic child
      behaviour. Blood glucose variability did not significantly contribute to this
      relationship. CONCLUSIONS: The stress experienced by parents of young children
      with chronic illness appears to relate to their perception of their children's
      behaviour problems. Parents' experiences with developmentally normative
      misbehaviour may interfere with disease management and exacerbate parents' stress
      and the subsequent impact on well-being. Implications for supporting parents and
      children with T1D are discussed.

PMID- 21083687
TI  - Maternal mental health and childrearing context in the development of children at
      6, 18 and 36 months: a Taiwan birth cohort pilot study.
AB  - BACKGROUND: This study investigated a possible pathway of the childrearing
      context and maternal mental health at 6 months, and how these factors influence
      children's development at 6, 18 and 36 months. METHODS: Using random sampling,
      2048 children and mothers were selected. The mother's health status was evaluated
      using the Taiwanese version of the 36-Item Short Form Health Survey (SF-36), and
      infant development was assessed using the high reliable Taiwan birth cohort study
      instrument. All data were collected using parental self-report, and were analysed
      using multiple linear regression analysis and further pathway using structural
      equation modelling. RESULTS: This study showed that 12 factors effected
      children's development at 6 months, and some dissipated with growth. Of these,
      maternal education had an enduring effect on different domains of child
      development, and this effect intensified as the child grew older. Children who
      grew up in a family with more siblings would show a delay in language development
      at 6 months; they have a delay in motor and social development at 18 and 36
      months. Additionally, maternal mental health effected the children's fine motor
      development at 6 months. However, this effect disappeared at 18 months, and
      influenced children's social development at 36 months. CONCLUSIONS: This study
      demonstrated that the development of children at as young as 6 months is affected
      by various factors. These factors may dissipate, continue to influence child
      development up to 3 years of age, turn from being disadvantageous to beneficial,
      or affect different domains of child development. Also, parental self-report
      instrument might be has its limitation and could be contributed by several
      confounding factors. Thus, continuous longitudinal follow-up on changes in
      maternal conditions, family factors, and environmental factors is vital to
      understand how these early infantile factors affect each other and influence the
      developmental trajectories of children into early childhood.

PMID- 21083688
TI  - Post-traumatic stress symptoms in childhood brain tumour survivors and their
      parents.
AB  - OBJECTIVES: This study aimed to investigate post-traumatic stress symptoms (PTSS)
      in childhood brain tumour survivors and their parents. A further aim was to
      explore the relationship between objective illness parameters, parent-child
      interactions, coping styles and PTSS. METHODS: A cross-sectional correlational
      design was employed. Fifty-two childhood brain tumour survivors, aged 8-16, and
      52 parents completed a battery of questionnaires designed to assess quality of
      parent-child interactions, monitoring and blunting attentional coping styles and
      PTSS. RESULTS: Over one-third (35%) of survivors and 29% of their parents
      reported severe levels of PTSS (suggestive of post-traumatic stress disorder
      'caseness'). Increased parent-child conflict resolution for survivors and number
      of tumour recurrences for parents independently predicted the variance in PTSS.
      CONCLUSIONS: For a substantial proportion of brain tumour survivors and their
      parents the process of survivorship is a considerably distressing experience.

PMID- 21083689
TI  - Siblings of children with cystic fibrosis: quality of life and the impact of
      illness.
AB  - OBJECTIVE: To asses self-reported quality of life (QoL) and perception of impact
      of illness on siblings of children with cystic fibrosis (CF). METHODS: The Child
      Health Questionnaire was used to assess QoL. The Sibling Perception Questionnaire
      was used to assess impact of illness. RESULTS: Siblings of children with CF (n=
      39) rated their QoL higher than siblings of healthy children on most QoL domains
      (e.g. Physical Functioning, Behavior, Mental Health). Siblings older than the
      child with CF reported a higher impact of CF than younger siblings. Perceived
      impact of illness was higher when the child with CF had been hospitalized or was
      intermittent or chronically infected with Pseudomonas aeruginosa. CONCLUSIONS:
      Siblings of children with CF reported a good QoL. QoL and impact of illness were
      related to indices of CF severity. Insight into sibling-issues helps CF teams to
      provide family-oriented care.

PMID- 21083690
TI  - Chinese parents' perceptions of their children's weights and their relationship
      to parenting behaviours.
AB  - PURPOSE: The purpose of this study is to examine Chinese parents' perceptions of
      their children's weights and explore the parenting behaviours associated with
      these perceptions. METHODS: A total of 2143 adolescents and 1869 parents were
      recruited from secondary schools in Ganzhou and Shantou in China. The
      adolescents' actual weights and heights were measured by trained testers. The
      self-reported parents' weights and heights, parental perception of the
      adolescents' weights, adolescents' perception of their own weights, parenting
      behaviours and demographic information were collected through the questionnaires
      distributed to the respondents. RESULTS: The results based on Kappa statistics
      show only a slight agreement between parental perception of their children's
      weights and the adolescents' actual weights (Kappa = 0.221). The results from the
      logistic regression show that the parents' gender [odds ratio (OR) = 0.80, 95%
      confidence interval (CI): 0.64-1.00], adolescents' gender (OR = 1.61, 95% CI:
      1.29-2.01) and perception of their own weights (OR = 0.30, 95% CI: 0.24-0.38) are
      associated with the parents' perception of their children's weights.
      Statistically significant difference in several parenting behaviours was found
      between the parents with correct and incorrect perceptions of their children's
      weight. DISCUSSION AND CONCLUSION: Misconceptions about their children's weights
      are prevalent among Chinese parents. The association between parents' perception
      of their children's weight and parenting behaviours suggests that the accurate
      classification of children's weights could help prevent childhood obesity.

PMID- 21083691
TI  - Governmental interventions and youth physical activity in France.
AB  - Data from a representative sample of 2474 French youth show that, despite a 7
      year French Ministry of Health strategy for nutrition and physical activities,
      adolescents' motivation to practise sports and physical activities decreased
      significantly between 2001 and 2008. While this paper focuses on the context of
      physical activity in France, the general discussion may be applicable to other
      countries concerned with the obesity pandemic.

PMID- 21083692
TI  - Childhood obesity: the extent of the problem among 6-year-old Irish national
      school children.
AB  - BACKGROUND: Childhood obesity is rapidly increasing worldwide. In Ireland, the
      number of overweight children has trebled over the last decade. The study aimed
      to provide an assessment of the prevalence of obesity of 6-year-old children in
      one region of Ireland. METHODS: Following training, School Public Health Nurses
      included the measurement of height and weight as part of the annual 'senior
      infants' school health check for 5453 6-year-old children in 189 schools between
      2004 and 2007. Body mass index (BMI) was calculated using the International
      Obesity Taskforce cut-off points using lmsGrowth (a Microsoft Excel add-in),
      which uses a child's exact age. Kendall's Tau b was used to determine the
      reliability of measurements. Prevalence trends were tested using multinomial
      logistic regression. Pearson's chi-squared test was utilized to assess the
      statistical significance of differences in BMI by gender, school year, and to
      compare with similar other Irish studies. RESULTS: Out of the 5453 children
      measured, 3493 were aged 6 years old. A further 11 were excluded because of
      incomplete data. Data were analysed for 3482 6-year-old children. Overall, 27% of
      6-year-olds were classified as either overweight or obese. A significantly
      greater proportion of girls are overweight or obese compared with boys (31%
      compared with 23%). Gender differences have remained relatively stable from 2004
      2007. Overall, there have been no significant changes in the level of obesity
      from 2004-2007. In addition, when comparing with other Irish studies that
      collected data for 2001/2, there are no significant differences in obesity
      levels. CONCLUSIONS: There is a clear need to urgently prioritize the effective
      management of obesity. Resourses should now be targeted towards ensuring
      government policies in Ireland and elsewhere are implemented.

PMID- 21083693
TI  - Rehabilitation for children with cerebral palsy in rural Cambodia: parental
      perceptions of family-centred practices.
AB  - BACKGROUND: Rehabilitation service providers in Cambodia are increasingly
      adopting family-centred practices when working with children with cerebral palsy
      and their families. This study examined the perceptions of parents living in
      rural Cambodia regarding family-centred rehabilitation practices. METHODS: This
      qualitative study used in-depth semi-structured individual and small group
      interviews with a convenience sample of 24 parents of children with cerebral
      palsy from three rural provinces. Participants were drawn from Cambodia Trust's
      client database and had been involved in a rehabilitation planning process which
      incorporated family-centred practices. RESULTS: Twenty-four parents and carers of
      children with cerebral palsy aged 3-12 years were interviewed. Almost all parents
      valued family-centred practices in rehabilitation, with many of the needs and
      preferences of parents living in rural Cambodia similar to those of parents in
      Western contexts. CONCLUSIONS: Family-centred approaches to paediatric
      rehabilitation were found to be valued in and appropriate for a rural Cambodian
      context. Social and cultural mechanisms to be considered when adapting a Western,
      family-centred model of rehabilitation planning to the rural Cambodian context
      include the hierarchical nature of Cambodian culture, the emphasis on group
      relational patterns rather than individual needs and the context of chronic
      poverty.

PMID- 21083694
TI  - Use of the Griffiths Mental Development Scales for children of the Philippines:
      some thoughts.

PMID- 21083695
TI  - Patterns of physical activity in Spanish children: a descriptive pilot study.
AB  - BACKGROUND: The majority of Spanish adults and children do not engage in enough
      physical activity to be beneficial for health. There is a need for objective and
      accurate assessment of the proportion of children meeting the physical activity
      recommendation for health. Assessing patterns of physical activity both between
      days (during weekdays and weekend days) and within days is of interest to improve
      our understanding of the variation in Spanish children's physical activity and to
      provide efficient intervention programmes. METHODS: A sample of 221 children: 136
      9-year-old children (68 boys and 68 girls) and 85 15-year-old children (36 girls
      and 49 boys) from 12 urban public schools in Madrid, Spain entered the study. The
      variables measured were anthropometric characteristics (height, weight, body mass
      index) and physical activity measured during four consecutive days using the GT1M
      accelerometer. RESULTS: Younger children were more active and less sedentary than
      older ones during week and weekend days. Nine-year-old boys and girls achieved
      significantly (P < 0.05) more moderate to vigorous physical activity (MVPA) and
      significantly (P < 0.01) less sedentary time than older 15-year-old children.
      During weekdays more children achieved physical activity recommendations versus
      weekend days. Physical activity patterns analyses indicated that boys achieved
      relatively high values of MVPA from 1100 till 1300 h (school break) and from 1800
      till 2000 h in comparison with the rest of the day. Girls were substantially
      different, with the 9-year-old girls having only two obvious peaks of weekday
      MVPA at lunch (1300) and after school (1900 h) while the adolescent girls had no
      clear peak of MVPA. CONCLUSIONS: Few children achieved the level of MVPA
      recommended for health; at particular risk were adolescent girls. More effort
      needs to be devoted to promoting appropriate opportunities for Spanish girls
      across the day and to promoting physical activity during weekends for all
      children.

PMID- 21083696
TI  - Salivary parameters in Brazilian individuals with cerebral palsy who drool.
AB  - BACKGROUND: Although drooling of saliva is considered abnormal in a child over 4
      years of age, it has been estimated to occur in approximately in 10-37% of
      children with cerebral palsy. AIM: The aim of this study was to evaluate the flow
      rate, pH and buffering capacity in saliva of Brazilian individuals with cerebral
      palsy who drool. METHODS: Cross-sectional assessment of saliva from 139
      individuals with cerebral palsy (3-16 years old) enrolled in a specialized
      rehabilitation centre in Sao Paulo, Brazil, divided into two groups, according to
      the presence (G1) or absence (G2) of drooling and controls (G3): G1 consisted of
      63 individuals who drool; G2 consisted of 76 who do not drool; and G3 consisted
      of 47 individuals with no neurological damage of similar age and sex.
      Unstimulated whole saliva was collected and salivary flow rate (mL/min), initial
      pH and buffering capacity, by titration of saliva with a constant amount of 0.01
      N HCl, were evaluated. The results from G1, G2 and G3 were compared by one-way
      anova and the chi(2) -test. RESULTS: A higher percentage of severe drooling
      (60.3%) was observed compared with moderate (27.0%) and mild (12.7%) in the
      cerebral palsy individuals who drool and the prevalence of drooling was highest
      among children and adolescents with spastic quadriplegia. Significant reductions
      in salivary flow rate, initial pH, buffering capacity of whole saliva in pH range
      6.0-6.9 and total buffering capacity occurred in G1 and G2 compared with G3.
      CONCLUSION: All individuals with cerebral palsy present lower flow rate, pH and
      buffering capacity of saliva, which increases the risk of oral diseases.

PMID- 21083697
TI  - Obesity, metabolic syndrome, adipocytes and vascular function: A holistic
      viewpoint.
AB  - 1. Obesity is a metabolic disease of pandemic proportions largely arising from
      positive energy balance, a consequence of sedentary lifestyle, conditioned by
      environmental and genetic factors. Several central and peripheral neurohumoral
      factors (the major ones being the anorectic adipokines leptin and adiponecin and
      the orexigenic gut hormone ghrelin) acting on the anorectic (pro-opiomelanocortin
      and cocaine- and amphetamine-regulated transcript) and orexigenic (neuropeptide Y
      and agouti gene-related protein) neurons regulate energy balance. These neurons,
      mainly in the arcuate nucleus of the hypothalamus, project to parts of the brain
      modulating functions such as wakefulness, autonomic function and learning. A tilt
      in the anorectic-orexigenic balance, perhaps determined genetically, leads to
      obesity. 2. Excess fat deposition requires space, created by adipocyte
      (hypertrophy and hyperplasia) and extracellular matrix (ECM) remodelling. This
      process is regulated by several factors, including several adipocyte-derived
      Matrix metalloproteinases and the adipokine cathepsin, which degrades
      fibronectin, a key ECM protein. Excess fat, also deposited in visceral organs,
      generates chronic low-grade inflammation that eventually triggers insulin
      resistance and the associated comorbidities of metabolic syndrome (hypertension,
      atherosclerosis, dyslipidaemia and diabetes mellitus). 3. The perivascular
      adipose tissue (PVAT) has conventionally been considered non-physiological
      structural tissue, but has recently been shown to serve a paracrine function,
      including the release of adipose-derived relaxant and contractile factors, akin
      to the role of the vascular endothelium. Thus, PVAT regulates vascular function
      in vivo and in vitro, contributing to the cardiovascular pathophysiology of the
      metabolic syndrome. Defining the mechanism of PVAT regulation of vascular
      reactivity requires more and better controlled investigations than currently seen
      in the literature.

PMID- 21083698
TI  - Metformin attenuates ventricular hypertrophy by activating the AMP-activated
      protein kinase-endothelial nitric oxide synthase pathway in rats.
AB  - 1. Metformin is an activator of AMP-activated protein kinase (AMPK). Recent
      studies suggest that pharmacological activation of AMPK inhibits cardiac
      hypertrophy. In the present study, we examined whether long-term treatment with
      metformin could attenuate ventricular hypertrophy in a rat model. The potential
      involvement of nitric oxide (NO) in the effects of metformin was also
      investigated. 2. Ventricular hypertrophy was established in rats by transaortic
      constriction (TAC). Starting 1 week after the TAC procedure, rats were treated
      with metformin (300 mg/kg per day, p.o.), N(G)-nitro-L-arginine methyl ester (L
      NAME; 50 mg/kg per day, p.o.) or both for 8 weeks prior to the assessment of
      haemodynamic function and cardiac hypertrophy. 3. Cultured cardiomyocytes were
      used to examine the effects of metformin on the AMPK-endothelial NO synthase
      (eNOS) pathway. Cells were exposed to angiotensin (Ang) II (10-6 mol/L) for 24 h
      under serum-free conditions in the presence or absence of metformin (10-3 mol/L),
      compound C (10-6 mol/L), L-NAME (10-6 mol/L) or their combination. The rate of
      incorporation of [3H]-leucine was determined, western blotting analyses of AMPK
      eNOS, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase
      (iNOS) were undertaken and the concentration of NO in culture media was
      determined. 4. Transaortic constriction resulted in significant haemodynamic
      dysfunction and ventricular hypertrophy. Myocardial fibrosis was also evident.
      Treatment with metformin improved haemodynamic function and significantly
      attenuated ventricular hypertrophy. Most of the effects of metformin were
      abolished by concomitant L-NAME treatment. L-NAME on its own had no effect on
      haemodynamic function and ventricular hypertrophy in TAC rats. 5. In
      cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect
      that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L
      NAME. The improvement in cardiac structure and function following metformin
      treatment was associated with enhanced phosphorylation of AMPK and eNOS and
      increased NO production. 6. The findings of the present study indicate that long
      term treatment with metformin could attenuate ventricular hypertrophy induced by
      pressure overload via activation of AMPK and a downstream signalling pathway
      involving eNOS-NO.

PMID- 21083699
TI  - Heat shock protein 90 mediates cytoprotection by H2S against chemical hypoxia
      induced injury in PC12 cells.
AB  - 1. Increasing evidence indicates that hydrogen sulphide (H2S) may serve as an
      important biological cytoprotective agent. Heat shock protein (Hsp) 90 can
      attenuate stress-induced injury. However, whether Hsp90 mediates the
      cytoprotective effect of H2S against chemical hypoxia-induced injury in PC12
      cells is not known. 2. In the present study, CoCl2 (a chemical hypoxia mimetic)
      was used to treat PC12 cells to create a model of chemical hypoxia. To explore
      the role of Hsp90 in the cytoprotection afforded by H2S against chemical hypoxia
      induced injury, 2 MUmol/L 17-allylaminogeldanamycin (17-AAG), a selective
      inhibitor of Hsp90, was administered for 30 min prior to preconditioning with 400
      MUmol/L NaHS, followed by chemical hypoxia. 3. Cobalt chloride reduced cell
      viability (by 52.7 +/- 1.5%), increased PC12 cell apoptosis (by 42.1 +/- 1.5%),
      induced reactive oxygen species (ROS) by 3.79% compared with control and induced
      the dissipation of mitochondrial membrane potential (MMP) by 2.56% compared with
      control. 4. Pretreatment of PC12 cells with 100-400 MUmol/L sodium hydrosulphide
      (NaHS), an H2S donor, for 3 h prior to exposure to 600 MUmol/L CoCl2 provided
      significant, concentration-dependant protection to PC12 cells against CoCl2
      induced cytotoxicity. Specifically, pretreatment of PC12 cells with 400 MUmol/L
      NaHS decreased apoptosis to 16.77 +/- 1.77% and blocked the CoCl2-induced
      increase in ROS production and loss of MMP. 5. At 400 MUmol/L, NaHS upregulated
      Hsp90 in a time-dependant manner (over the period 0-180 min). In addition to its
      effects on Hsp90 expression, NaHS pretreatment of PC12 cells augmented the
      overexpression of Hsp90 induced by 600 MUmol/L CoCl2 by 1.38-fold (P < 0.01). 6.
      Treatment of PC12 cells with 2 MUmol/L 17-AAG for 30 min prior to NaHS
      pretreatment blocked the overexpression of Hsp90 induced by NaHS preconditioning,
      as evidenced by decreased cell viability (by 54.2 + 1.2%; P < 0.01), increased
      PC12 cell apoptosis (by 36.6 +/- 1.2%; P < 0.01) and increasing ROS production.
      7. The findings of the present study provide novel evidence that Hsp90 mediates
      H2S-induced neuroprotection against chemical hypoxia-induced injury via anti
      oxidant and anti-apoptotic effects.

PMID- 21083701
TI  - Comparative split-face study of 5-aminolevulinic acid photodynamic therapy with
      intense pulsed light for photorejuvenation of Asian skin.
AB  - Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT) using
      intense pulsed light (IPL) as a light source (IPL-ALA-PDT) has been used for
      photorejuvenation, but it is unclear if this protocol can be applied to darker
      skin types. We performed this study to assess our IPL-ALA-PDT protocol for
      photorejuvenation in Asian skin. To determine an appropriate dose, ALA ointment
      (0-20%) was applied to the upper arm of five healthy volunteers and the
      fluorescence intensity (FI) was measured using a spectrofluorometer. Non-linear
      regression analysis of FI 2 h after ALA application with global fitting gave a
      typical sigmoid dose-response curve with R2 = 0.9705 and saturation after 5% ALA.
      The entire faces of 16 Japanese women with photodamage were then treated with IPL
      (500-670 and 870-1400 nm, 23-30 J/cm2) 2 h after application of 5% ALA to one
      side of the face. Three treatments were delivered at 4-week intervals with follow
      up visits. Comparative analysis of photorejuvenation showed noticeable
      improvements on both sides of the face, although the reduction in the photoaging
      score from baseline did not differ significantly between the two sides in all
      subjects. Despite this finding, 75% of the patients felt that the IPL-ALA-PDT
      treated side of the face showed greater improvement than the IPL-treated side.
      However, all IPL-ALA-PDT-treated sides showed adverse effects such as erythema
      and pain. Therefore, we conclude that the IPL-ALA-PDT protocol requires
      optimization for photorejuvenation in Asians.

PMID- 21083702
TI  - Histogenesis of congenital and acquired melanocytic nevi based on histological
      study of lesion size and thickness.
AB  - The histogenesis of melanocytic nevi is poorly understood. It is important to
      determine the differences and similarities in histogenesis between congenital and
      acquired nevi. To clarify the histogenic differences between acquired melanocytic
      nevi (AMN) and congenital melanocytic nevi (CMN), diameter and depth of nevus
      cells (tumor thickness) were examined in histological specimens from 80 cases of
      CMN and 71 cases of AMN, and these nevi were classified according to Mark's
      pathological CMN criteria. In all cases, giant CMN nevus cells were found in the
      lower marginal portion of excised specimens. The mean diameter and lesional
      thickness were significantly higher in CMN than in AMN. AMN diameter showed a
      significant correlation (r = 0.567, P < 0.05) with lesional thickness, while no
      such relation was observed in CMN. In addition, a significant correlation between
      lesion diameter and thickness was observed in small (<10 mm) non-Mark's type CMN
      (r = 0.626, P < 0.05). CMN may be classified into three subtypes: (i) caused by
      increased proliferation of melanoblasts during the course of migration from the
      neural crest to the epidermis; (ii) proliferation of nevus cells after arrival at
      the epidermis, and nevus cell distribution affected by adnexa and dermal
      differentiation; and (iii) arising after completion of skin development before
      birth.

PMID- 21083700
TI  - Relationship between serum osteocalcin and glycaemic variability in Type 2
      diabetes.
AB  - 1. Recent reports have described the role of osteocalcin in glucose metabolism
      and glycaemic variability has been proven to be associated with an increased risk
      of diabetes complications. However, the relationship between osteocalcin and
      glycaemic variability remains unclear. The aim of the present study was to
      examine the relationship between serum osteocalcin and glycaemic variability, as
      determined by a continuous glucose monitoring (CGM) system in patients with Type
      2 diabetes mellitus (T2DM). 2. Fifty-nine T2DM patients with glycosylated
      haemoglobin (HbA1c) levels between 7.0% and 10.9% were recruited to the present
      study. Biochemical information and CGM parameters were collected at baseline and
      after 8 weeks of antihyperglycaemic therapy (either sulphonylurea, sulphonylurea
      + an alpha-glucosidase inhibitor or insulin + metformin combination therapy). 3.
      Compared with baseline, serum osteocalcin increased significantly (P = 0.014),
      whereas parameters related to glucose variability, including the mean amplitude
      of glycaemic excursions (MAGE) and the standard deviation of blood glucose
      values, decreased significantly (P < 0.001) after the 8 week treatment period. At
      baseline, there was a positive correlation between serum osteocalcin levels and
      fasting C-peptide levels (P = 0.004) and homeostatic model assessment of beta
      cell function (P = 0.048), but a negative correlation between serum osteocalcin
      levels and fasting plasma glucose (P = 0.023), HbA1c (P = 0.020), glycated
      albumin (P = 0.019) and 24 h mean blood glucose (P < 0.001). Multiple stepwise
      regression analysis indicated that baseline osteocalcin was the single parameter
      that best predicted the change in MAGE (beta = -0.122; P = 0.039). 4. In
      conclusion, serum osteocalcin concentrations increased with improved glucose
      control. High initial osteocalcin levels were associated with subsequent
      improvements in glucose variability during glucose-lowering treatment.

PMID- 21083703
TI  - Objective evaluation of photoepilation by phototrichogram.
AB  - Photoepilation is one of the most popular cosmetic procedures. However, there has
      been no objective method to evaluate the efficacy of hair removal. The goal of
      this study is to evaluate the effect of photoepilation more objectively using a
      phototrichogram method. Thirteen young, healthy, female volunteers were enrolled
      in this study. At initial work-up, semi-permanent tattoos were marked in both
      axillae of all the volunteers and hair variables were evaluated by
      phototrichogram and digital camera. Intense pulsed light-assisted photoepilations
      were performed in both axillae of the volunteers twice at 4-week intervals. At
      each visit, dermatologists checked changes of hair parameters. Clinically, 8
      weeks after two treatments, hair reduction of all patients was achieved. Total
      hair counts, changes of anagen ratio, non-vellus hair counts, hair density,
      anagen growth rate and hair diameter were decreased sequentially and the
      reduction was statistically significant. No correlations were found between
      power, pain, patient and doctor evaluations at 4 weeks. Doctor evaluations
      correlated with anagen hair counts, anagen/total hair ratio, anagen/telogen ratio
      and total growth rate. Using phototrichograms could be an objective evaluation
      technique for hair removal. Anagen parameters and total growth rate of hairs in
      phototrichograms may be able to be predictable values for evaluating epilation.

PMID- 21083704
TI  - Mosquito allergy: clinical features and natural course.
AB  - Mosquito bite allergic reactions are due to sensitization to mosquito salivary
      proteins. The purpose of our study was to assess the clinical features of Thai
      patients with mosquito allergy, and to define the natural desensitization course.
      Seventy patients with mosquito allergy were enrolled. Most patients were female.
      Half of the patients had a personal history of atopy. The average age of onset of
      mosquito reaction was 5.7 years old (range 2-58). Four patients were in the
      desensitization phase in which clinical symptoms disappeared within 9.5 years
      (median). The common cutaneous lesions were erythematous papules (68.6%) and
      immediate wheals (67.1%). The most common area of involvement was the leg. Forty
      of 50 patients (80%) had positive skin prick testing to mosquito allergen (Culex
      quinquefasciatus) and 31 of 42 patients (73.8%) had positive immunoglobulin E
      antibodies against allergens in C. quinquefasciatus saliva proteins.

PMID- 21083705
TI  - Treatment of alopecia areata with 308-nm excimer lamp.
AB  - Alopecia areata is considered to be a T-cell mediated autoimmune disorder. The
      308-nm excimer lamp is thought to be capable of inducing T-cell apoptosis in
      vitro, suggesting that the lamp might be effective for the treatment of alopecia
      areata. We examined the effectiveness of the 308-nm excimer lamp for the
      treatment of alopecia areata. We recruited three patients with single alopecia
      areata lesions that were resistant to conventional treatment. The lesions were
      exposed to a 308-nm excimer lamp at 2-weekly intervals. Hair regrowth was
      observed in all three patients after approximately 10 treatment sessions. Our
      study showed that exposure to the 308-nm excimer lamp effectively induced hair
      regrowth in solitary alopecia areata lesions. Apart from erythema, there were no
      significant adverse effects. Therefore, we suggest that it may be considered as a
      treatment modality for recalcitrant alopecia areata.

PMID- 21083706
TI  - Scleredema diabeticorum successfully treated with ultraviolet A1 phototherapy.
AB  - Scleredema diabeticorum is an uncommon condition. It is one of the cutaneous
      manifestations in diabetes mellitus that mainly occurs in obese middle-aged men
      with insulin-resistant diabetes. This condition is generally recalcitrant to
      therapy. Various treatments have been tried with inconsistent results. Here, we
      describe two cases of scleredema diabeticorum with substantial clinical
      improvement from a course of medium dose (60 J/cm2) ultraviolet A1 radiation
      therapy.

PMID- 21083707
TI  - Two cases of mycosis fungoides treated by reduced-intensity cord blood
      transplantation.
AB  - Mycosis fungoides is a cutaneous T-cell lymphoma, which is clinically divided
      into three stages: patch, plaque and tumor. Despite a variety of treatments the
      prognosis is poor in advanced mycosis fungoides. Recently, allogeneic
      hematopoietic stem cell transplantation has been successfully applied for such
      cases. We performed reduced-intensity umbilical cord blood transplantation for
      two advanced mycosis fungoides patients. Case 1 was a 56-year-old man and case 2
      was a 30-year-old woman. Tumors of each case were refractory to conventional
      chemotherapy. Although radiation therapy was considerably effective, tumors
      relapsed after several months. Reduced-intensity umbilical cord blood
      transplantation was performed because case 1 had no human leukocyte antigen
      identical siblings and the sibling of case 2 did not agree to be the donor. The
      male patient died of pulmonary failure 23 days after reduced-intensity umbilical
      cord blood transplantation. The case 2 patient succeeded in reduced-intensity
      umbilical cord blood transplantation and remained in complete/partial remission
      for 13 months. However, chemotherapy-resistant tumors relapsed, and allogeneic
      hematopoietic stem cell transplantation was performed at 17 months. She died of
      cerebral hemorrhage 23 days after the procedure. Reduced-intensity umbilical cord
      blood transplantation may be included in the treatments for advanced mycosis
      fungoides, where graft-versus-lymphoma effect seems to be a significant factor
      for the success of the treatment.

PMID- 21083708
TI  - Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in collagen disease
      patient.
AB  - Phaeohyphomycosis is a rare fungal infection that is more commonly associated
      with compromised patients. We present herein an 81-year-old man with collagen
      disease and chronic interstitial pneumonia who developed subcutaneous
      phaeohyphomycosis caused by Exophiala jeanselmei. The main pathogen of
      phaeohyphomycosis had been considered to be E. jeanselmei complex. This has
      recently been divided into several species by using a molecular technique. The
      main pathogen of phaeohyphomycosis is Exophiala xenobiotica, and E. jeanselmei is
      rather a rare pathogen of this disease. Although p.o. itraconazole and
      terbinafine administration was not effective for this patient, these antifungal
      agents were used for preventing systemic dissemination in this immunocompromised
      host.

PMID- 21083709
TI  - Two novel splice site mutations of the ADAR1 gene in Chinese families with
      dyschromatosis symmetrica hereditaria.

PMID- 21083710
TI  - CD147 is highly expressed on peripheral blood neutrophils from patients with
      psoriasis and induces neutrophil chemotaxis.

PMID- 21083711
TI  - Recent onset vitiligo treated with systemic corticosteroid and topical
      tacrolimus: Need for early treatment in vitiligo.

PMID- 21083712
TI  - Psoriasis verrucosa.

PMID- 21083713
TI  - Superimposed linear psoriasis.

PMID- 21083714
TI  - Successful treatment of chronic urticaria with a Japanese herbal medicine,
      yokukansan.

PMID- 21083716
TI  - Progressive nodular histiocytosis.

PMID- 21083715
TI  - Importance of sentinel lymph node biopsy in Merkel cell carcinoma.

PMID- 21083717
TI  - Childhood abuse and fear of childbirth--a population-based study.
AB  - BACKGROUND: Childhood abuse affects adult health. The objective of this study was
      to examine the association between a self-reported history of childhood abuse and
      fear of childbirth. METHODS: A population-based, cross-sectional study was
      conducted of 2,365 pregnant women at five obstetrical departments in Norway. We
      measured childhood abuse using the Norvold Abuse Questionnaire and fear of
      childbirth using the Wijma Delivery Expectancy Questionnaire. Severe fear of
      childbirth was defined as a Wijma Delivery Expectancy Questionnaire score of >=
      85. RESULTS: Of all women, 566 (23.9%) had experienced any childhood abuse, 257
      (10.9%) had experienced emotional abuse, 260 (11%) physical abuse, and 290
      (12.3%) sexual abuse. Women with a history of childhood abuse reported severe
      fear of childbirth significantly more often than those without a history of
      childhood abuse, 18 percent versus 10 percent (p = 0.001). The association
      between a history of childhood abuse and severe fear of childbirth remained
      significant after adjustment for confounding factors for primiparas (adjusted OR:
      2.00; 95% CI: 1.30-3.08) but lost its significance for multiparas (adjusted OR:
      1.17; 95% CI: 0.76-1.80). The factor with the strongest association with severe
      fear of childbirth among multiparas was a negative birth experience (adjusted OR:
      5.50; 95% CI: 3.77-8.01). CONCLUSIONS: A history of childhood abuse significantly
      increased the risk of experiencing severe fear of childbirth among primiparas.
      Fear of childbirth among multiparas was most strongly associated with a negative
      birth experience.

PMID- 21083718
TI  - Elective cesarean delivery: does it have a negative effect on breastfeeding?
AB  - BACKGROUND: Cesarean delivery has negative effects on breastfeeding. The
      objective of this study was to evaluate breastfeeding rates, defined in
      accordance with World Health Organization guidelines, from delivery to 6 months
      postpartum in infants born by elective and emergency cesarean section and in
      infants born vaginally. METHODS: Delivery modalities were assessed in relation to
      breastfeeding patterns in 2,137 term infants delivered at a tertiary center, the
      Padua University School of Medicine in northeastern Italy, from January to
      December 2007. The study population included 677 (31.1%) newborns delivered by
      cesarean section, 398 (18.3%) by elective cesarean, 279 (12.8%) by emergency
      cesarean section, and 1,496 (68.8%) delivered vaginally. RESULTS: Breastfeeding
      prevalence in the delivery room was significantly higher after vaginal delivery
      compared with that after cesarean delivery (71.5% vs 3.5%, p < 0.001), and a
      longer interval occurred between birth and first breastfeeding in the newborns
      delivered by cesarean section (mean +/- SD, hours, 3.1 +/- 5 vs 10.4 +/- 9, p <
      0.05). No difference was found in breastfeeding rates between the elective and
      emergency cesarean groups. Compared with elective cesarean delivery, vaginal
      delivery was associated with a higher breastfeeding rate at discharge and at the
      subsequent follow-up steps (7 days, 3 mo, and 6 mo of life). CONCLUSIONS:  
      Emergency and elective cesarean deliveries are similarly associated with a
      decreased rate of exclusive breastfeeding compared with vaginal delivery. The
      inability of women who have undergone a cesarean section to breastfeed
      comfortably in the delivery room and in the immediate postpartum period seems to
      be the most likely explanation for this association.

PMID- 21083719
TI  - Examining autonomy's boundaries: a follow-up review of perinatal mortality cases
      in UK independent midwifery.
AB  - BACKGROUND: An earlier matched cohort study in the United Kingdom found a
      significantly higher perinatal mortality rate for births booked under an
      independent midwife compared with births in National Health Service units (1.7%
      [25/1,508] vs 0.6% [45/7,366]). This study examined independent midwives'
      management and decision making in the 15 instances of perinatal death that
      occurred at term. METHODS: Thematic analysis of independent midwives' case notes
      was performed in instances of perinatal mortality. Semi-structured interviews
      were conducted with the midwives concerned. RESULTS: Home birth was attempted in
      13 of the 15 cases. Significant (often multiple) antenatal risk factors were
      identified in 13 cases, including twin pregnancy, planned vaginal births after
      cesarean section, breech presentations, and maternal illness. Several women had
      declined some or all routine antenatal screening. Three deaths occurred before
      labor onset. Postmortem results were known in only four cases; many causes of
      death remained unexplained. Professional consensus was that seven deaths were
      unpreventable; elective cesarean section may have changed the outcome in eight
      cases. However, the pregnant women had declined this option; some were reported
      to be avoiding National Health Service care because of previous bad experiences.
      Transfer to hospital care, when it occurred, was often problematic. Care
      management was judged to be clinically acceptable within the parameters set by
      the mothers' choices. CONCLUSIONS: Information about clinical processes (and
      outcomes) is essential if informed decisions are to be made. The women in this
      review had reportedly accepted the potential consequences of their high-risk
      situations. If reality is to match rhetoric about "patient" autonomy, such
      decision making in high-risk situations must be accepted.

PMID- 21083720
TI  - Birth preferences that deviate from the norm in Sweden: planned home birth versus
      planned cesarean section.
AB  - BACKGROUND: Opting for a home birth or requesting a cesarean section in a culture
      where vaginal birth in a hospital is the norm challenges the health care system.
      The aim of this study was to compare background characteristics of women who
      chose these very different birth methods and to see how these choices affected
      factors of care and the birth experience. METHODS: This descriptive study
      employed a secondary data analysis of a sample of women who gave birth from 1997
      to 2008, including 671 women who had a planned home birth and 126 women who had a
      planned cesarean section based on maternal request. Data were collected by means
      of questionnaires. Logistic regression with crude and adjusted odds ratios (OR)
      with a 95 percent confidence interval (95% CI) was calculated. RESULTS: Women
      with a planned home birth had a higher level of education (OR: 2.3; 95% CI: 1.5
      3.6), were less likely to have a high body mass index (OR: 0.1; 95% CI: 0.01
      0.6), and were less likely to be smokers (OR: 0.2; 95% CI: 0.1-0.4) when compared
      with women who had planned cesarean sections. When adjusted for background
      variables, women with a planned home birth felt less threat to the baby's life
      during birth (OR: 0.1; 95% CI: 0.03-0.4), and were more satisfied with their
      participation in decision making (OR: 6.0; 95% CI: 3.3-10.7) and the support from
      their midwife (OR 3.9; 95% CI: 2.2-7.0). They also felt more in control (OR: 3.3;
      95% CI: 1.6-6.6), had a more positive birth experience (OR: 2.9; 95% CI: 1.7
      5.0), and were more satisfied with intrapartum care (OR: 2.3; 95% CI: 1.3-4.1)
      compared with women who had a planned cesarean section on maternal request.
      CONCLUSIONS: Women who planned a home birth and women who had a cesarean section
      based on maternal request are significantly different groups of mothers in terms
      of sociodemographic background. In a birth context that promotes neither home
      birth nor cesarean section without medical reasons, we found that those women who
      had a planned home birth felt more involvement in decision making and had a more
      positive birth experience than those who had a requested, planned cesarean
      section.

PMID- 21083722
TI  - Commentary: Nonpharmacological approaches to hypertension in pregnancy need
      further evaluation.

PMID- 21083721
TI  - Effects of guided imagery on blood pressure in pregnant women with hypertension:
      a pilot randomized controlled trial.
AB  - BACKGROUND: Hypertension occurs in nearly 10 percent of pregnancies, and is
      associated with higher risk of infant and maternal morbidity and mortality than
      in normal pregnancies. Previous studies have suggested that relaxation therapies
      reduce blood pressure in nonpregnant adults. The objectives of this pilot
      randomized trial were to provide preliminary evidence of whether relaxation by
      means of guided imagery would reduce blood pressure in hypertensive pregnant
      women, and to assess the feasibility of a larger trial. METHODS: A total of 69
      pregnant women with hypertension were randomized to periods of guided imagery or
      of quiet rest, twice daily for 4 weeks or until delivery, whichever came first.
      Daytime ambulatory mean arterial pressure, systolic and diastolic blood pressure,
      and anxiety were measured weekly for up to 4 weeks. RESULTS: Women allocated to
      guided imagery had lower mean arterial pressure elevations over time than those
      allocated to quiet rest (guided imagery: M = 1.58 mmHg, SD = 7.63; quiet rest: M
      = 5.93 mmHg, SD = 6.55; t = 2.36, p = 0.02). However, when adjusted for baseline
      mean arterial pressure and gestation, the effect was not significant (p = 0.14).
      Numbers of women prescribed antihypertensive medication postrandomization were
      similar (guided imagery: n = 16; quiet rest: n = 13, chi(2) = 0.74, p = 0.46).
      There was also no evidence of an effect on women's anxiety. Nearly 90 percent (n
      = 26) of the guided imagery group indicated that they would use it again.
      CONCLUSIONS: Further rigorous study is warranted to determine effects of guided
      imagery on maternal blood pressure and perinatal health outcomes.

PMID- 21083723
TI  - Women's experiences of empowerment in a planned home birth: a Swedish population
      based study.
AB  - BACKGROUND: Childbirth can be an empowering event in a woman's life. However,
      little is known about women's own perceptions of power and empowering sources
      during childbirth. This study aimed to describe the factors experienced as
      empowering during a planned home birth. METHODS: The inclusion criteria were
      women in Sweden who had a planned home birth between 1992 and 2005. All the women
      (n = 735) who agreed to participate received one questionnaire for each planned
      home birth. A total of 1,038 questionnaires were sent to the women. The written
      birth stories were analyzed using content analysis and descriptive statistics.
      RESULTS: In the analysis of the participants' birth experience four categories
      and one overall theme emerged from the stories. The categories identified were
      sensations, guidance, tacit support, and identification of needs. Greater
      emphasis was put on guidance among first-time mothers than among multiparas, for
      whom tacit support was identified as the most empowering factor. The overall
      theme was identified as "resting in acceptance of the process." The empowerment
      women expressed by achieving and maintaining a sense of control allowed them to
      rest in acceptance of the efforts that are part of a normal birth. CONCLUSION:
      Women who choose to give birth at home find empowering sources within themselves
      from their environment and from the active and passive support of persons they
      have chosen to be present at the birth.

PMID- 21083724
TI  - Exploring dental care misconceptions and barriers in pregnancy.
AB  - BACKGROUND: Poor oral health is increasingly linked to adverse pregnancy
      outcomes, including preterm birth and low-birthweight infants. Little is known
      about childbearing women's experiences in obtaining dental care. The objective of
      this study was to explore Florida women's experience of barriers in obtaining
      dental care before and during their pregnancies. METHODS: Study data were derived
      from a larger data set of a study that examined barriers to prenatal care. One
      month after giving birth face-to-face interviews were conducted with 253 African
      American women, 18 to 35 years old, who were residents of one of three Florida
      counties. Interview questions about women's experiences on obtaining oral health
      care before and during pregnancy, and recall of guidance about oral health care
      during prenatal visits were transcribed and analyzed qualitatively. Through
      subject-level content analysis, key themes were assessed about the participants'
      perspectives on obtaining oral health care before and during pregnancy. RESULTS:
      Most participants did not obtain dental care and did not recall receiving dental
      information during prenatal visits. Barriers to dental care included lack of
      insurance, difficulty in finding a dentist, low priority given to dental care,
      misconceptions about the safety and appropriateness of dental care during
      pregnancy, and sporadic anticipatory guidance during prenatal care. CONCLUSIONS:
      Misconceptions about the appropriateness of oral health care during pregnancy may
      affect women's access to and use of this care. Given the implications of poor
      oral health on possible adverse birth outcomes and its larger connection with the
      general health of mothers and babies, attention to oral health misconceptions and
      barriers is warranted.

PMID- 21083725
TI  - Bridging the gap between textbook and maternity patient: a nurse-developed
      teaching model for first-year medical students.
AB  - BACKGROUND: Providing more opportunities for first-year medical students to
      interact with patients in clinical settings is a current discussion topic in
      medical student education reform. Early clinical experience helps students bridge
      the gap between textbook and patient while observing patient-centered care, and
      serves as a first step for students to develop the skills needed to work
      cooperatively as members of a multidisciplinary health care team. The author
      developed a model to provide perinatal education to first-year medical students,
      consistent with the concept of interprofessional education. METHODS: Primarily
      first-year medical students participated in the nurse-developed education model,
      a component of a noncredit extracurricular, student-run perinatal program at a
      Midwestern university medical center. Students were placed at the bedsides of
      hospitalized women to provide support and education to them during perinatal
      procedures, labor, childbirth, and cesarean delivery. RESULTS: A total of 350
      students participated over a period of 13 school calendar years. Students
      remarked that participation in the program reinforced the importance of their
      concurrent anatomy and physiology classes. They observed interdependence and
      cooperation among the members of the health care team caring for women, and their
      evaluations of their experiences at the bedside were highly positive. Women
      consistently expressed appreciation for the additional individualized attention
      and education received from our student and nurse team. CONCLUSIONS: Nurses can
      enhance the learning of first-year medical students in the maternity care
      clinical setting. This nurse-developed education program provided students with a
      variety of vivid clinical experiences with maternity patients.

PMID- 21083726
TI  - The patient observer: sterile water injections for labor pain.
AB  - Several studies have reported a good pain relief effect from sterile water
      injections, especially for low back pain, during labor. The aim of this paper was
      to illustrate the use of the method in a clinical childbirth situation by means
      of a descriptive case report. The woman in the report described that the method
      provided a powerful pain relief effect, measured by a visual analog scale, and
      that her experience was highly positive.

PMID- 21083727
TI  - U.S. health care reform legislation offers major new gains to childbearing women
      and newborns.

PMID- 21083728
TI  - Home birth: gone away, gone astray, and here to stay.
AB  - Home birth has attracted a great deal of attention of late, culminating in a meta
      analysis to assess its risks for mother and baby. Mothers were estimated to be
      2.6 times more likely to die and babies 3 times more likely to die from a planned
      home birth than from a planned hospital birth. The actual data on which these
      estimates were based demonstrate that meta-analysis can be developed into an art
      that suits whatever purpose its authors hope to achieve. Combining studies of
      home versus hospital, without differentiating what is inside them, where they
      are, and what is around them, is akin to producing a fruit salad with potatoes,
      pineapples, and celery.

PMID- 21083734
TI  - Does prosthodontic rehabilitation change the eating patterns among completely
      edentulous patients?
AB  - OBJECTIVE:  Nutrition is compromised in completely edentulous individuals. As
      there is limited literature available on the nutritional health of the elderly in
      the Indian population, the present study was undertaken to assess these changes
      before and 1 month after placement of complete dentures in a dental hospital in
      Indore, Madhya Pradesh, India. MATERIALS AND METHODS: The 10-item closed-ended
      questionnaire was completed by the investigator who interviewed the subjects (n =
      35) before placement of complete dentures and 1 month later. RESULTS: A
      statistically significant difference was found for having an illness or condition
      that led to a change in the type and/or amount of food eaten (p = 0.013); eating
      few fruits, vegetables, or milk products (p = 0.005) and having oral problems
      that made it difficult to eat (p = 0.003). CONCLUSIONS: Prosthodontic
      rehabilitation improved the eating pattern with increased intake of fruits,
      vegetables and milk products.

PMID- 21083731
TI  - Prenatal yoga and depression during pregnancy.

PMID- 21083735
TI  - Southern Nevada assisted living residents' perception of their oral health status
      and access to dental care.
AB  - OBJECTIVE: Oral health is an integral component of general health, and quality of
      life. The purpose of this study was to determine the perceptions of oral health
      status and acces?s to dental care by Southern Nevada Assisted Living Facilities
      Residents. METHODS: A cross-sectional questionnaire study design was used to
      survey residents between 34 and 99 years old residing in Assisted Living
      Facilities. Seventy respondents (42 males and 28 females) completed a survey that
      included personal oral hygiene, access to care, and demographic information. Data
      analyses included descriptive statistics and chi-square. RESULTS: Mean age was
      75.78 years, and the majority had a college education (n = 41). Four currently
      smoked cigarettes. Twenty-nine (males = 14; females = 15) reported having dental
      insurance. Eleven respondents had seen a dentist twice a year, while 33 reported
      a visit less than 6 months. Forty-one reported the facility did not provide oral
      health care with majority (n = 64) indicating that accessing oral health care was
      difficult. Self-rated response to oral hygiene, a majority (n = 64) reported
      their oral hygiene as fair and five reported their oral hygiene as poor.
      CONCLUSIONS: Assisted living residents in Southern Nevada reported difficulty
      accessing dental services within and outside of the facility. Oral care models to
      address this unique population should be explored.

PMID- 21083736
TI  - Clinical evaluation of three denture cushion adhesives by complete denture
      wearers.
AB  - OBJECTIVE: The aim of this study was the clinical evaluation of three denture
      cushion adhesives and whether the results were correlated to Kapur Index for
      denture-supporting tissues. BACKGROUND: Various types of denture adhesives are
      used among denture patients. However, information on the clinical behaviour of
      denture cushions is limited. MATERIALS AND METHODS: Thirty edentulous patients
      had their denture-supporting tissues scored by Kapur Index and their old dentures
      replaced. They received three brands of denture cushion adhesives (Fittydent((r))
      , Protefix((r)) and Seabond((r))) and were instructed to use them in a sequence
      according to the group they were randomly assigned to. Each brand of adhesive was
      used for 48 h on the lower denture according to the manufacturer's suggestions.
      After each brand was used, participants spent 24 h without applying any sort of
      adhesive. Finally, a questionnaire evaluating and comparing the performance of
      each brand was filled out. RESULTS: Denture adhesives generally improved patient
      satisfaction and masticatory ability, especially in participants with poor Kapur
      Index and those who reported a poor retention of their old dentures. CONCLUSION:
      Fittydent((r)) was the most preferred adhesive, showing the best retention and
      the longest duration of its effect, but also reported as difficult to remove from
      the denture-bearing area.

PMID- 21083737
TI  - Evaluation of experimental cleanser solution of Ricinus communis: effect on soft
      denture liner properties.
AB  - OBJECTIVE: This study evaluated colour stability, hardness and roughness of soft
      denture liners after immersion in various cleansers. MATERIALS AND METHODS:
      Thirty specimens (14 mm * 4 mm) of Elite Soft Relining (ES) and Mucopren Soft
      (MS) were randomly immersed in distilled water at 37 degrees C, sodium
      hypochlorite 1%, and an experimental Ricinus communis solution (RC) for 7, 15 and
      183 continuous days. RESULTS: anova (p < 0.05) and Tukey's test indicated that
      after T7 (MU =8.79 +/- 7.36); T15 (MU = 4.23 +/- 2.62) and T183 (MU = 8.78 +/-
      3.16), MS presented a higher increase in hardness than ES. After T7, MS underwent
      an increase in roughness (MU = 0.09 +/- 0.80); ES underwent a decrease (MU = 
      0.08 +/- 0.16). RC caused the smallest variation in roughness. After T15, both
      materials presented an increase in roughness. After T183, ES (MU = -0.30 +/-
      0.48) presented a higher roughness variation than MS (MU = -0.07 +/- 0.32).
      Hypochlorite caused an increase in roughness (MU = 0.02 +/- 0.19). CONCLUSION:
      After all periods ES presented higher colour alteration than MS; highest colour
      alteration was caused by hypochlorite. Both materials were more stable after
      immersion in RC.

PMID- 21083738
TI  - Denture disinfection by microwave energy: influence of Candida albicans biofilm.
AB  - OBJECTIVE: This study evaluated the influence of the area of Candida albicans
      biofilm on denture disinfection by microwave energy. MATERIALS AND METHODS:
      Candida albicans biofilm was allowed to form for 72 h on resin discs, and three
      small coverage or seven large coverage discs were placed onto the palatal surface
      of sterile maxillary dentures. Each denture was immersed in 200 ml distilled
      water and individually irradiated at a power of 450, 630 or 900 W for different
      time intervals (1, 2 or 3 min) (n = 6). The effectiveness of disinfection was
      evaluated by counting the residual cells. The data were analysed by anova and
      Tukey's HSD test (alpha = 0.05). Pearson's correlation test was performed to
      determine the correlation between effectiveness of sterilisation and temperature.
      RESULTS: Dentures with a larger area of biofilm demanded a longer irradiation
      exposure to achieve disinfection (p < 0.001), irrespective of power setting, and
      in this time no yeast growth was detected. Dentures with small areas of biofilm
      were disinfected after 1 min at 900 W and 2 min at 450 or 630 W. A positive
      correlation was found between water temperature and effectiveness of disinfection
      (r = 0.6170; p < 0.001). CONCLUSION: The C. albicans biofilm area influenced
      disinfection by microwave energy; therefore dentures with larger biofilm areas
      required longer irradiation exposure to be disinfected.

PMID- 21083739
TI  - Loss of natural dentition: multi-level effects among a geriatric population.
AB  - OBJECTIVE: To quantify the impact of edentulousness on residual ridge volume,
      denture stomatitis (DS), as well as oral health behaviours among geriatric
      denture-wearers. BACKGROUND: Residual ridge resorption (RRR) is the primary
      intraoral complication of complete edentulism, but individual variation among
      geriatric patients has been observed. MATERIALS AND METHODS: Data collection
      relied upon a 10-year retrospective chart review of all complete denture-wearing
      geriatric patients presenting at the Removable Prosthodontics Clinic, Dental
      School of Athens, between 1993 and 2002. Analyses relied on descriptive,
      bivariate, and multivariate methods based on ordinal logistic regression.
      RESULTS: A total of 873 records of geriatric patients (age mean = 72; median =
      70; range = 65-95) comprised our analytical sample. Subjects' mean (SD) time
      since edentulation was 7.7 (10.2) years. Eleven percent were diagnosed with
      temporomandibular disorder (TMD). While 28% of patients reported cleaning their
      dentures at least daily, 6% presented with denture stomatitis (DS). Each added
      year of edentulism increased the odds of mandibular RRR: OR (95% CI) = 1.05
      (1.03, 1.07). Nightly denture wear was the strongest risk factor for DS. Finally,
      independent of age and sex, each year of being edentulous increased the odds of
      presenting with TMD: OR (95% CI) = 1.03 (1.01, 1.05). CONCLUSION: Time since
      edentulation was strongly associated with mandibular but not maxillary RRR, as
      well as TMD development.

PMID- 21083740
TI  - Possible relationship between periodontitis and dementia in a North Indian old
      age population: a pilot study.
AB  - BACKGROUND: Periodontitis and cognitive impairment or dementia is relatively
      common among older adults. Few cross-sectional studies and some longitudinal
      studies have attempted to link oral health with dementia diagnosis or disease
      pathology but none has investigated the role of inflammation as a potential
      mediator. OBJECTIVES: This study was planned to establish a relation of
      inflammatory mediators between periodontitis and dementia. MATERIALS AND METHODS:
      Fifty-five patients with severe periodontitis (range 60-69 years), 20 with
      dementia (10:10 M:F; range 59-69) and 32 healthy controls (range 58-69 years)
      were selected. The socio-demographic characteristics, physical health, oral
      health, education status, and medical status were measured. Serum C-reactive
      protein (CRP), matrix metalloproteinase (MMP)-8, MMP-9, total IGF-I, free IGF-I
      and TNF-alpha and GCF MMP-8 &MMP-9 were calculated. RESULTS: There was no
      significant difference between the three groups in the level of education, age,
      occupation, BMI, CAD, CHF and diabetes except dentate status. After adjusting for
      age, significant differences were found between patients and controls with
      respect to gingival inflammation, dental plaque, bleeding on probing and probing
      pocket depth. Total counts of WBCs, neutrophils, thrombocytic counts and serum
      CRP, MMP-8, MMP-9, TNF-alpha levels were significantly higher in dementia and
      periodontitis patients in contrast to healthy controls, while, RBC counts, total
      IGF-I and Hb levels were lowered in dementia and periodontitis patients in
      comparison to healthy controls, although higher in dementia as compared to
      periodontitis patients. CONCLUSIONS: This study data suggest a relationship of
      inflammatory mediators between periodontitis and dementia. Further exploration of
      this is warranted.

PMID- 21083741
TI  - A conventional microwave oven for denture cleaning: a critical review.
AB  - INTRODUCTION: Denture cleaning should be quick and easy to perform, especially in
      long-term care facilities. The lack of proper oral hygiene can put older adults
      at higher risk from opportunistic oral infections, particularly fungal. As an
      alternative to regular brushing, the use of a microwave oven has been suggested
      for cleaning and disinfecting dentures. OBJECTIVES: To synthesise and discuss the
      advantages and disadvantages of the use of a conventional microwave oven for
      cleaning and disinfecting complete dentures. METHODS: A brief literature search
      focused on papers dealing with microwave therapy for denture cleaning through
      PubMed Central, Cochrane Database of Systematic Reviews, Google Scholar, Ovid
      MEDLINE(R) In-Process, and Scifinder Scholar. RESULTS: One hundred and sixty
      seven manuscripts published in English with full text were found, and 28 were
      accepted and discussed in the light of the advantages and disadvantages of the
      use of conventional microwave oven for cleaning and disinfecting complete
      dentures. CONCLUSIONS: There was no standardisation for microwave use for denture
      cleaning. Manual cleaning still seemed to be the optimal method for controlling
      fungal infection and denture stomatitis. However, such a daily routine appeared
      to be underused, particularly in long-term care facilities.

PMID- 21083742
TI  - Analysis of socio-demographic and systemic health factors and the normative
      conditions of oral health care in a population of the Brazilian elderly.
AB  - OBJECTIVE: To investigate the association of socio-demographic and systemic
      health factors according to the normative conditions of oral health care (dental
      caries, edentulism, periodontal disease and oral mucosal lesion) in elderly
      individuals. MATERIAL AND METHODS: A cross-sectional study was carried out in a
      group of elderly with access to community health care (n = 200). The normative
      conditions of oral health were then investigated according to the WHO and the SB
      Brazil criteria. Bivariate analyses were evaluated by the chi-square test and
      Fisher's exact test. An estimation of prevalence for the covariates was performed
      using Poisson's regression models. RESULTS: The prevalence of edentulism and oral
      mucosal lesions was detected in 58% and 21.5% of elderly patients, respectively.
      In the dentate subjects, the prevalence of dental caries and periodontal disease
      was 51.2% and 20.8%, respectively. Older men and individuals from lower-income
      groups exhibited a higher prevalence of dental caries. Elderly women, illiterate
      individuals, and individuals over the age of 65 years exhibited a higher
      prevalence of edentulism. Elderly 60-64 years old and those who are employed had
      a significant association with periodontal disease. CONCLUSION: Socio-demographic
      factors were associated with some notable oral diseases in the elderly.

PMID- 21083743
TI  - Effect of thermocycling on hardness, absorption, solubility and colour change of
      soft liners.
AB  - OBJECTIVE: The effect of artificial ageing on the hardness, absorption,
      solubility, and colour of soft denture liners was investigated. MATERIALS AND
      METHODS: Liner materials based on acrylic resin (Trusoft) or silicone (Dentusil,
      Ufi Gel P, and Ufi Gel SC) were tested before and after 2000 thermal cycles. A
      total of 20 specimens of each material were tested. Half of the specimens were
      used for hardness and colour evaluation, and the remainder for absorption and
      solubility tests. The hardness evaluation was carried out using a Shore A
      durometer, while absorption and solubility tests were performed by storing
      samples in a desiccator and weighing daily until reaching constant mass (W1).
      After thermocycling, the samples were again weighed (W2) and dried (W3). Colour
      was measured using a spectrophotometer. Statistical analysis was performed using
      GraphPad InStat at the p < 0.05 level. RESULTS: Thermocycling significantly
      affected the hardness of the specimens. The Trusoft material exhibited the
      highest absorption (1.48 +/- 0.48), solubility (1.26 +/- 0.28), and colour change
      (3.92 +/- 0.33), significantly different from the other materials. There were no
      significant differences among the silicones in terms of absorption, solubility,
      and colour change, except for the colour of Dentusil, which changed (0.83 +/-
      0.11). CONCLUSION: It can be concluded that silicone liners performed
      significantly better compared to acrylic resin.

PMID- 21083744
TI  - Oral hygiene and periodontal disease in Victorian nursing homes.
AB  - OBJECTIVE: To investigate oral hygiene and periodontal disease in residents of
      Victoria nursing homes. BACKGROUND:   The Australian population is ageing with a
      growing proportion of elderly Australians living in nursing homes. With declining
      edentulism rates, periodontal disease is becoming more prevalent in this
      population. MATERIALS AND METHODS: A total of 275 dentate residents from 31
      Victorian nursing homes had a questionnaire and clinical examination using the
      Visual Plaque Index and a modified Community Periodontal Index. RESULTS: Self
      reported oral hygiene habits of residents were poor, with less than one-third of
      residents cleaning their teeth twice daily or more. Periodontal health was found
      to be extremely poor, and the prevalence of 4 mm+ periodontal pockets was 35.6%,
      with 10.2% having 6 mm+ pockets. Logistic regression found that age, gender,
      number of teeth present and oral hygiene were all strongly associated with the
      prevalence of 4 mm+ periodontal pockets. CONCLUSION: Poor oral hygiene and the
      presence of significant plaque and calculus were common findings in this study.
      Periodontal diseases are a significant problem for residents in nursing homes.
      Addressing this health issue will require improved training for carers and better
      access to appropriate dental services.

PMID- 21083745
TI  - Investigation of oral opportunistic pathogens in independent living elderly
      Japanese.
AB  - OBJECTIVE: Pneumonia is reported to be associated with high morbidity in elderly
      and compromised individuals, with poor oral health demonstrated to be a
      significant risk factor for pneumonia. Several opportunistic pathogens, such as
      Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli and
      Staphylococcus aureus, have been detected in patients with pneumonia. We
      investigated the prevalence of opportunistic pathogens in the oral cavity of
      healthy independent living Japanese elderly subjects and analysed factors related
      to harbouring those pathogens. MATERIALS AND METHODS: We studied 265 subjects,
      each of whom received a dental examination, during which specimens were collected
      with a tongue swab and examined for the presence of 10 oral opportunistic
      pathogens using single or multiple selective media. Furthermore, the presence of
      occult blood in saliva was examined using test paper strips. RESULTS: Oral
      opportunistic pathogens were detected in 13.6% of the subjects. Those positive
      for occult blood in saliva had a significantly higher rate of harbouring the
      pathogens (p < 0.05). In addition, age was a significant factor for the presence
      of pathogenic microbes in the oral cavity (p = 0.033). CONCLUSION: Positive
      findings of occult blood in saliva and older age are suggested to be significant
      factors for harbouring opportunistic pathogens in the oral cavity.

PMID- 21083747
TI  - Helicobacter pylori infection may be implicated in the topography and geographic
      variation of upper gastrointestinal cancers in the Taihang Mountain high-risk
      region in northern China.
AB  - BACKGROUNDS: Helicobacter pylori infection is prevalent in China. Chronic
      infection of the bacterial not only causes distal stomach cancer, but also
      confers risk to gastric cardia adenocarcinoma. Because H. pylori infection is
      inversely associated with esophageal adenocarcinoma, globally the infection rate
      is significantly correlated with the ratio of squamous carcinoma to
      adenocarcinoma of the esophagus. These agree with the topography of upper
      gastrointestinal cancer observed in the Taihang Mountain high-risk region where
      both gastric cardia and non-cardia adenocarcinoma coincide with esophageal
      squamous cancer, but with almost no distal esophageal adenocarcinoma. Moreover,
      as altitude increases from plain to mountains, we observed progressively
      increasing incidence rates of gastric adenocarcinomas in recent years in the
      region. Because H. pylori infection is a definite carcinogen to gastric
      adenocarcinoma and is more prevalent in the mountain than in plain areas due to
      undeveloped living conditions, the observation gives the impression as though H.
      pylori infection is implicated. AIMS: This article aims to note the role of H.
      pylori infection in upper gastrointestinal cancer in the Taihang Mountain high
      risk region in northern China. MATERIALS AND METHODS: First the unique topography
      and geographic variation of upper gastrointestinal cancer in the region is
      described to indicate a possible role of H. pylori infection, then we review
      studies on prevalence of H. pylori infection in the high-risk region and describe
      difference in socioeconomic development and water hygiene between the plains and
      the mountains as related to the prevalence of H. pylori infection. RESULTS:  
      Coincidence of gastric cancer in the region and a progressively increasing rate
      of the cancer from the plain towards the mountains indicate H. pylori infection
      may be implicated in upper gastrointestinal cancer. CONCLUSION: International
      collaboration is needed to study H. pylori and upper gastrointestinal cancer in
      the region when rapid industrialization is just beginning.

PMID- 21083746
TI  - Morphologic, genetic, and biochemical characterization of Helicobacter
      magdeburgensis, a novel species isolated from the intestine of laboratory mice.
AB  - BACKGROUND: The presence of enterohepatic Helicobacter species (EHS) is commonly
      noted in mouse colonies. These infections often remain unrecognized but can cause
      severe health complications or more subtle host immune perturbations and
      therefore can confound the results of animal experiments. The aim of this study
      was to isolate and characterize a putative novel EHS that has previously been
      detected by PCR screening of specific-pathogen-free mice. MATERIALS AND METHODS: 
      Biochemical analysis of enzyme activities (API campy), morphologic investigation
      (Gram-staining and electron microscopy) and genetic analyses (16SrRNA and 23SrRNA
      analyses, DNA fingerprinting, restriction fragment polymorphisms, and pulsed
      field gel electrophoresis) were used to characterize isolated EHS. Genomic DNA
      fragments were sequenced to develop a species-specific PCR detection assay.
      RESULTS: Scanning electron microscopy revealed the presence of spiral-shaped EHS,
      which varied in length (2.5-6 MUm) and contained single monopolar or single
      bipolar sheathed flagella. The bacteria were grown under anaerobic conditions,
      preferably on agar plates containing serum or blood. The 16SrRNA, genetic, and
      biochemical analyses indicated the identification of a novel EHS species, named
      Helicobacter magdeburgensis. We also examined the genome content using pulsed
      field gel electrophoresis. Based on the pattern produced by two restriction
      enzymes, BamIII and KspI, the genome size was determined to be about 1.7-1.8 Mbp.
      CONCLUSION: We isolated and characterized a novel EHS species, H. magdeburgensis,
      morphologically, biochemically, and genetically. These results are important for
      future studies on the prevalence and pathophysiologic relevance of such
      infections. Our PCR assay can be used to detect and discriminate H.
      magdeburgensis from other Helicobacter species.

PMID- 21083748
TI  - The bifidogenic growth stimulator inhibits the growth and respiration of
      Helicobacter pylori.
AB  - BACKGROUND: Triple therapy with amoxicillin, clarithromycin, and a proton-pump
      inhibitor is a common therapeutic strategy for the eradication of Helicobacter
      pylori (H. pylori). However, frequent appearance of clarithromycin-resistant
      strains is a therapeutic challenge. While various quinones are known to
      specifically inhibit the growth of H. pylori, the quinone 1,4-dihydroxy-2
      naphthoic acid (DHNA) produced by Propionibacterium has strong stimulating effect
      on Bifidobacterium. We were interested to see whether DHNA could inhibit the
      growth of H. pylori in in vitro or in vivo experimental setting. MATERIALS AND
      METHODS: The minimum inhibitory concentration (MIC) of DHNA was determined by the
      agar dilution method. The inhibitory action of DHNA on the respiratory activity
      was measured by using an oxygen electrode. Germ-free mice infected with H. pylori
      were given DHNA in free drinking water containing 100 MUg/mL for 7 days. RESULTS:
      DHNA inhibited H. pylori growth at low MIC values, 1.6-3.2 MUg/mL. Likewise, DHNA
      inhibited clinical isolates of H. pylori, resistant to clarithromycin. However,
      DHNA did not inhibit other Gram negative or anaerobic bacteria in the normal
      flora of the human intestine. Both H. pylori cellular respiration and adenosine
      5'-triphosphate (ATP) generation were dose-dependently inhibited by DHNA.
      Similarly, the culture filtrates of propionibacterial strains inhibited the
      growth of H. pylori, and oral administration of DHNA could eradicate H. pylori in
      the infected germ-free mice. CONCLUSIONS: The bifidogenic growth stimulator DHNA
      specifically inhibited the growth of H. pylori including clarithromycin-resistant
      strains in vitro and its colonization activity in vivo. The bactericidal activity
      of DHNA was via inhibition of cellular respiration. These actions of DHNA may
      have clinical relevance in the eradication of H. pylori.

PMID- 21083749
TI  - Expression of Helicobacter pylori TonB protein in transgenic Arabidopsis
      thaliana: toward production of vaccine antigens in plants.
AB  - BACKGROUND: The aim of this study was to produce a recombinant version of the
      highly antigenic Helicobacter pylori TonB (iron-dependent siderophore transporter
      protein HP1341) in transgenic plants as a candidate oral vaccine antigen.
      MATERIALS AND METHODS: Using Agrobacterium-mediated gene transfer, we introduced
      three different constructs of the tonB gene into the genome of the model plant
      Arabidopsis thaliana. We investigated transgene insertion by PCR, produced TonB
      antibodies for analysis of the production of the recombinant protein in plants,
      verified the identity of the protein produced by mass spectrometry analysis, and
      analyzed the number of genetic inserts in the plants by Southern blotting.
      RESULTS: Three different constructs of the expression cassette (full-length tonB,
      tonB truncated in the 5' end removing the codons for a transmembrane helix, and
      the latter construct with codons for the endoplasmic reticulum SEKDEL retention
      signal added to the 3' end) were used to find the most effective way to express
      the TonB antigen. Production of TonB protein was detected in plants transformed
      with each of the constructs, confirmed by both Western blotting and mass
      spectrometry analysis. No considerable differences in protein expression from the
      three different constructs were observed. The protein concentration in the plants
      was at least 0.05% of the total soluble proteins. CONCLUSIONS: The Helicobacter
      pylori TonB protein can be produced in Arabidopsis thaliana plants in a form that
      is recognizable by rabbit anti-TonB antiserum. These TonB-expressing plants are
      highly suitable for animal studies of oral administration as a route for
      immunization against Helicobacter infections.

PMID- 21083750
TI  - Helicobacter pylori induction of the gastrin promoter through GC-rich DNA
      elements.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection has been linked to the
      development of chronic gastritis, duodenal ulcer disease, and gastric cancer.
      Helicobacter pylori- infected patients and animal models develop
      hypergastrinemia, chronic gastritis, and gastric atrophy. Since gastrin is an
      important regulator of gastric acid secretion and cell growth, H. pylori
      regulation of this hormone has been implicated in its pathogenesis. OBJECTIVES:
      To investigate the effect of H. pylori on gastrin gene expression in mice and of
      human bacterial isolates on gastrin mRNA expressed in a human cell line. METHODS:
      Gastrin mRNA was measured by qRT-PCR in H. pylori-infected mice. H. pylori were
      co-cultured with AGS cells to study regulation of human gastrin gene expression.
      Various MAP kinases were implicated in signal transduction from the bacteria
      using specific inhibitors. Gastrin reporter constructs and gel shift assays were
      used to map DNA responsive elements. RESULTS: In addition to an increase in
      gastrin mRNA in H. pylori-infected mice, H. pylori induced the endogenous human
      gastrin gene through MAP kinase-dependent signaling but not NFkappaB-dependent
      signaling. Activation of gastrin through MAPK signaling did not require CagA or
      VacA virulence factors. Transfection studies demonstrated that a GC-rich motif
      mediated H. pylori-induction of the gastrin promoter and that the motif inducibly
      binds Sp1 and Sp3 transcription factors. CONCLUSIONS: Direct contact of live H.
      pylori bacteria with human cells is sufficient to induce gastrin gene expression.

PMID- 21083751
TI  - Short-term therapy with celecoxib and lansoprazole modulates Th1/ Th2 immune
      response in human gastric mucosa.
AB  - BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors and proton pump
      inhibitors may exert immune-mediated effects in human gastric mucosa. T-cell
      immune response plays a role in Helicobacter pylori-induced pathogenesis. This
      study evaluated effects of celecoxib and lansoprazole on T-helper (Th) 1 and Th2
      immune response in human gastric mucosa. METHODS: Dyspeptic patients with or
      without osteoarticular pain were given one of the following 4-week therapies:
      celecoxib 200 mg, celecoxib 200 mg plus lansoprazole 30 mg, and lansoprazole 30
      mg daily. Expression of COX-2, T-bet, and pSTAT6 and production of prostaglandin
      E2 (PGE2), interferon (IFN)-gamma, and interleukin (IL)-4 were determined in
      gastric biopsies before and after therapy. Histology was evaluated. RESULTS:
      Cyclooxygenase-2 expression and PGE2 production was higher, and Th1 signaling
      pathway was predominant in H. pylori-infected vs. uninfected patients. T-bet
      expression and IFN-gamma production increased, while STAT6 activation and IL-4
      production decreased following therapy with celecoxib and celecoxib plus
      lansoprazole, respectively. Th1 and Th2 signaling pathways down-regulated after
      therapy with lansoprazole, and this was associated with an improvement of
      gastritis. Effect of therapy was not affected by H. pylori status. CONCLUSION:
      Celecoxib and lansoprazole modulate Th1/Th2 immune response in human gastric
      mucosa. The use of these drugs may interfere with long-term course of gastritis.

PMID- 21083752
TI  - The evolution of Helicobacter pylori antibiotics resistance over 10 years in
      Beijing, China.
AB  - OBJECTIVES: To evaluate Helicobacter pylori antibiotics resistance evolution from
      2000 to 2009 to amoxicillin, clarithromycin, metronidazole, tetracycline,
      levofloxacin and moxifloxacin in Beijing, China. METHODS: A total of 374 H.
      pylori strains isolated from 374 subjects who had undergone upper
      gastrointestinal endoscopy from 2000 to 2009 were collected and examined by E
      test method for antibiotics susceptibility. RESULTS: The average antibiotics
      resistance rates were 0.3% (amoxicillin), 37.2% (clarithromycin), 63.9%
      (metronidazole), 1.2% (tetracycline), 50.3% (levofloxacin) and 61.9%
      (moxifloxacin). Overall resistance to clarithromycin, metronidazole, and
      fluoroquinolone increased annually (from 14.8 to 65.4%, 38.9 to 78.8%, and 27.1
      to 63.5%, in 2000 or 2006-2007 to 2009, respectively). The secondary resistance
      rates were much higher than primary rates to these antibiotics, which also
      increased annually in recent 10 years. CONCLUSIONS: The trend of clarithromycin,
      metronidazole, and fluoroquinolone resistance of H. pylori increased over time
      and the resistance to amoxicillin and tetracycline was infrequent and stable in
      Beijing. Clarithromycin, metronidazole, and fluoroquinolone should be used with
      caution for H. pylori eradication treatment.

PMID- 21083753
TI  - Is the association between Helicobacter pylori infection and anemia age
      dependent?
AB  - BACKGROUND: The relationship between H. pylori infection and anemia in childhood
      is still unclear. The aim of the study was to examine the association between H.
      pylori infection and anemia or iron deficiency in school-age children and in
      infants. MATERIALS AND METHODS: Six- to 9-year-old Israeli Arab children (N =
      202) and infants (N = 197) were examined for hemoglobin and ferritin levels.
      ELISA was used to detect H. pylori antigens in stool specimens collected from the
      participants. Household characteristics were obtained through personal interviews
      with the mothers. RESULTS: The prevalence of anemia was 15.5 versus 5.5% in H.
      pylori-positive and -negative school-age children, respectively and 34.5 versus
      29.8% in H. pylori-positive and -negative infants, respectively. The Mantel
      Haenszel age-adjusted prevalence ratio (PR) and 95% confidence intervals (CIs)
      were 1.6 (95%CI 1.0, 2.6). In multivariate analysis controlling for socioeconomic
      variables, H. pylori infection was associated with 2.8 higher prevalence of
      anemia only in school-age children: adjusted PR 2.8 (95% CI 0.9, 9.3). The
      adjusted mean difference in hemoglobin levels between H. pylori infected school
      age children and uninfected ones was -0.372 gr/dL (95% CI -0.704, -0.039) (p =
      .04). The respective mean ferritin difference was -6.74 MUg/L (95% CI -13.38, 
      .011) (p = .04). Such differences were not found in infants. CONCLUSIONS: H.
      pylori infection is associated with higher prevalence of anemia in school-age
      children independently of socioeconomic variables. Such association was not
      observed in infants. These findings are of clinical and public health importance.

PMID- 21083754
TI  - Viability determination of Helicobacter pylori using propidium monoazide
      quantitative PCR.
AB  - BACKGROUND: While Helicobacter pylori exists in a bacillary form in both the
      natural habitat and the human host, detrimental environmental circumstances have
      been observed to lead to the conversion of H. pylori from the bacillary to the
      coccoid form. However, the viability or nonviability of coccoid forms remains to
      be established in H. pylori. The aim of this study was to determine whether the
      quantitative PCR combined with propidium monoazide could be an alternative and
      good technique to determine H. pylori viability in environmental samples and, to
      contribute to understanding of the role of the H. pylori forms. MATERIALS AND
      METHODS: Viability, morphological distribution, and the number of live H. pylori
      cells were determined using a propidium monoazide-based quantitative PCR method,
      at various time points. RESULTS: Under adverse environmental conditions was
      observed the conversion of H. pylori from the bacillary to the coccoid form, and
      the decrease in amplification signal, in samples that were treated with propidium
      monoazide, over the time. CONCLUSIONS: Incorporation of propidium monoazide
      indicates that there is an increase in H. pylori cells with the damaged membrane
      over the study, leading to the manifestation of cellular degeneration and death.
      Consequently, quantitative PCR combined with propidium monoazide contributes to
      our understanding of the role of H. pylori cells, under adverse environmental
      conditions.

PMID- 21083756
TI  - Impact of TLR-4 polymorphisms on circulating levels of antibodies against
      Helicobacter pylori.

PMID- 21083755
TI  - Maintenance of Helicobacter pylori cultures in agar stabs.
AB  - BACKGROUND: Helicobacter pylori requires frequent passage at 37  degrees C with
      reduced oxygen tension to maintain viability, and recovery from frozen stocks can
      be unpredictable and slow. Agar stab cultures were assessed as a possible means
      of maintaining viability without the need to passage every 4-7 days. MATERIALS
      AND METHODS: Agar stabs prepared from either Brucella or Brain Heart Infusion
      media were inoculated deeply with H. pylori strains or H. felis and grown under
      varying conditions for up to 13 weeks. Subcultures were prepared from these stabs
      at various intervals to test for viability. RESULTS: Established cultures in agar
      stabs failed to survive at room temperature but did survive at 37  degrees C with
      10% CO2 for up to 56 days. H. felis remained viable for up to 28 days. No
      difference was observed between the two media formulations. CONCLUSION: H. pylori
      grown in agar stabs remains viable for prolonged periods of time without the need
      to subculture and may represent an improved method for storing H. pylori for
      infrequent use.

PMID- 21083757
TI  - Clinical findings in children with cutaneous anthrax in eastern Turkey.
AB  - Anthrax is a zoonosis produced by Bacillus anthracis. The aim of this study was
      to evaluate the clinical findings, therapy, and outcome in children with
      cutaneous anthrax (CA). Data on age, gender, occupation, clinical symptoms and
      findings, location and type of lesions, clinical history, laboratory findings,
      treatment, and outcome were recorded from patients' medical records,
      retrospectively. The study included 65 patients between 1 month and 18 years old
      (9.0+/-4.0 years), 37 patients (56.9%) were male and 28 (43.1%) were female. Most
      of the patients (89.1%) were admitted in summer and autumn (p<0.001). Of the 65
      patients, 20 patients (30.8%) had received antibiotherapy before admission to our
      hospital. All patients except one had a contact history with infected animals. A
      1-month-old patient had a contact history with his mother who had CA. On clinical
      examination, anthrax edema was noted in 36 (55.3%) patients, anthrax pustule in
      27 (41.5%), and anthrax edema and anthrax pustule in two (3%) patients. Gram
      staining and culture was positive for B. anthracis in 35 (53.8%) patients, and
      only Gram staining was positive in 10 (15.4%) patients. In the remaining 20
      (30.8%) patients, the diagnosis was made by clinical findings. Because the
      anthrax outbreak in Turkey was associated with slaughtering or milking of ill
      cows, sheep, or goats, and handling raw meat without taking any protective
      measures, persons in the community must be educated about using personal
      protective equipment during slaughtering of animals and handling of meat and
      skins.

PMID- 21083758
TI  - Persistent fifth aortic arch: echocardiographic diagnosis of a persistent fifth
      aortic arch.

PMID- 21083759
TI  - Optical quality and intraocular scattering in a healthy young population.
AB  - BACKGROUND: We objectively assessed the optical quality and intraocular
      scattering by means of parameters provided by a clinical double-pass system in
      healthy young subjects and thereby we obtained new reference data for clinical
      diagnosis. We calculated normal values of neural contrast sensitivity function
      (nCSF) from the measured modulation transfer function (MTF) and the contrast
      sensitivity function (CSF). METHODS: Eligible subjects were healthy adults aged
      from 18 to 30 years with a logMAR visual acuity (VA) of 0.0 or better and normal
      values of CSF. Optical quality measurements for a 4.0 mm pupil were performed
      using the Optical Quality Analysis System (OQAS) based on the double-pass
      technique. The following parameters were analysed: the modulation transfer
      function cutoff frequency (MTF(cutoff)), the Strehl(2D) ratio, the OQAS values
      (OV) at 100, 20 and nine per cent contrasts and the objective scatter index
      (OSI). RESULTS: A total of 178 volunteers responded to the call, of whom 181 eyes
      were finally part of the study taking into account the criteria for inclusion.
      The values for the optical quality parameters were: 44.54 +/- 7.14 cpd
      (MTF(cutoff)), 0.27 +/- 0.06 (Strehl(2D) ratio), 1.48 +/- 0.24 (OV(100%)), 1.58
      +/- 0.32 (OV(20%)), 1.64 +/- 0.39 (OV(9%)), and 0.38 +/- 0.19 (OSI). The nCSF
      calculated was 1.76 +/- 0.21 (3 cpd), 2.13 +/- 0.23 (6 cpd), 2.01 +/- 0.28 (12
      cpd) and 1.86 +/- 0.33 (18 cpd). CONCLUSION: The normal values provided can be a
      useful tool for discriminating healthy eyes from early abnormal ones in which the
      optical quality or sensory function is impaired.

PMID- 21083760
TI  - Review of resistance of ocular isolates of Pseudomonas aeruginosa and
      staphylococci from keratitis to ciprofloxacin, gentamicin and cephalosporins.
AB  - BACKGROUND: Microbial keratitis is a rare disease but most commonly caused by
      bacterial infection. Two of the most common bacteria to cause microbial keratitis
      are Pseudomonas aeruginosa and Staphylococcus aureus. Antibiotic therapy to treat
      keratitis caused by these bacteria is either monotherapy with a fluoroquinolone
      or combination therapy with fortified gentamicin. METHODS: Literature searches
      were made in Medline and Pubmed using the search terms [Pseudomonas] or
      [Staphylococcus] and [fluoroquinolone] or [cephalosporin] or [gentamicin] and
      [keratitis] or [cornea]. Rates of resistance to ciprofloxacin, gentamicin or
      cephalosporins were then compared for isolates from different geographic regions.
      RESULTS: There are low resistance rates of P. aeruginosa and S. aureus to
      ciprofloxacin in isolates from Australia. Isolates from the Indian subcontinent
      are more commonly resistant to ciprofloxacin, with resistance rates of greater
      than 20 per cent being reported. Data from USA and Europe indicate that if the S.
      aureus is a methicillin resistant strain, then resistance to ciprofloxacin
      increases, often to greater than 80 per cent of isolates. Resistance to
      gentamicin and cephalosporins is also generally low in isolates from Australia.
      Again resistance is increased in isolates from the Indian subcontinent, as well
      as from South America. CONCLUSION: In Australia, the major ocular pathogens are
      generally sensitive to the most commonly used antibiotics to treat microbial
      keratitis. The prescription of fluoroquinolones, aminoglycosides and
      cephalosporins is generally reserved for treatment of significant or sight
      threatening conditions such as microbial keratitis. This approach is not likely
      to contribute to an increase in resistance rates.

PMID- 21083762
TI  - The why, what, and how of global biodiversity indicators beyond the 2010 target.
AB  - The 2010 biodiversity target agreed by signatories to the Convention on
      Biological Diversity directed the attention of conservation professionals toward
      the development of indicators with which to measure changes in biological
      diversity at the global scale. We considered why global biodiversity indicators
      are needed, what characteristics successful global indicators have, and how
      existing indicators perform. Because monitoring could absorb a large proportion
      of funds available for conservation, we believe indicators should be linked
      explicitly to monitoring objectives and decisions about which monitoring schemes
      deserve funding should be informed by predictions of the value of such schemes to
      decision making. We suggest that raising awareness among the public and policy
      makers, auditing management actions, and informing policy choices are the most
      important global monitoring objectives. Using four well-developed indicators of
      biological diversity (extent of forests, coverage of protected areas, Living
      Planet Index, Red List Index) as examples, we analyzed the characteristics needed
      for indicators to meet these objectives. We recommend that conservation
      professionals improve on existing indicators by eliminating spatial biases in
      data availability, fill gaps in information about ecosystems other than forests,
      and improve understanding of the way indicators respond to policy changes.
      Monitoring is not an end in itself, and we believe it is vital that the ultimate
      objectives of global monitoring of biological diversity inform development of new
      indicators.

PMID- 21083761
TI  - Efficacy of azithromycin 1% ophthalmic solution for treatment of ocular surface
      disease from posterior blepharitis.
AB  - BACKGROUND: Posterior blepharitis is an eyelid disease primarily of the meibomian
      glands. Bacteria and chronic inflammation are contributing factors for meibomian
      gland disease, which leads to ocular surface and tear film alterations and
      chronic patient symptoms. Azithromycin 1.0% ophthalmic solution is a broad
      spectrum topical antibiotic with anti-inflammatory properties. The present study
      evaluates the efficacy of azithromycin 1.0% ophthalmic solution in the treatment
      of the clinical signs and symptoms, including vision-related function, associated
      with meibomian gland dysfunction. METHODS: In an open label study, 33 patients
      with meibomian gland dysfunction were treated with azithromycin 1.0% ophthalmic
      solution twice a day for two days, then every evening for a total of 30 days.
      Tear break-up time, corneal staining, conjunctival staining, Schirmer scores with
      anaesthetic, meibomian gland score and patient's symptom scores were evaluated at
      baseline and after 30 days of treatment. The Ocular Surface Disease Index (OSDI)
      was administered at baseline, after two weeks of treatment and after 30 days of
      treatment. RESULTS: Twenty-six of 33 patients completed the study. Tear break-up
      time and Schirmer score increased by 52.7 per cent (p < 0.0001) and 24 per cent
      (p < 0.05), respectively. There was a reduction in corneal and conjunctival
      staining by 83.2 and 67.9 per cent, respectively (p < 0.0001). Lid margin scores
      were reduced by 33.9 per cent (p < 0.0001). The patient's symptom score improved
      from 2.73 at baseline to 2.21 after 30 days of treatment (p < 0.01). The mean
      OSDI at baseline was 34.44. After two weeks and 30 days of treatment, the ODSI
      was 14.51 and 13.15 respectively (p < 0.0001). CONCLUSION: These results
      demonstrate clinically and statistically significant improvement in the signs and
      symptoms associated with posterior blepharitis. Based on these results,
      azithromycin 1% ophthalmic solution offers a viable option for the treatment of
      posterior blepharitis.

PMID- 21083763
TI  - Management of peripheral vascular disease compromising renal allograft placement
      and function: review of the literature with an illustrative case.
AB  - As the average age of a renal transplant candidate increases, the challenge of
      managing recipient vascular disease affecting renal allograft function will
      become more common. Pre-operative screening can reveal the presence of
      atheromatous disease that could adversely affect allograft transplantation and
      function, but parameters for successful screening have not been established.
      Treatment options include pre-operative revascularization, concurrent therapy or
      delayed revascularization. Endovascular therapies have burgeoned but surgical
      correction is still required for some of the more complex, long-segment lesions.
      Potential surgical interventions range from endarterectomy to aorto-iliac
      bypasses. We present a case of immediate post-operative revascularization using a
      femoro-femoral bypass to salvage a renal allograft. The literature is reviewed to
      assess best practices for detecting peripheral vascular disease in renal
      transplant candidates and subsequent management options.

PMID- 21083764
TI  - Similar prevalence but different characteristics of pain in kidney transplant
      recipients and chronic hemodialysis patients.
AB  - BACKGROUND: Chronic pain is frequent in both hemodialysis (HD) patients and
      kidney transplant (KTx) recipients but its detailed characteristics have never
      been thoroughly investigated. AIM: To compare prevalence of pain, its locations
      and characteristics, and analgesics use in chronic HD and KTx patients. METHODS:
      A cross-sectional comparative study in 164 HD patients and 114 stable deceased
      donor KTx recipients. All participants completed the modified McGill Pain
      Questionnaire. RESULTS: Overall, 63% of HD patients and 62% of KTx patients
      reported pain. Fifty-four percent of HD patients and 67% of KTx patients
      indicated more than one location of pain. Severe pain was more common in HD
      patients, and prevalence of pain-associated symptoms from major body systems was
      higher in HD patients. Pain in both groups was mostly local, paroxysmal and/or
      chronic. Fifteen percent of HD patients and 37% of KTx patients with chronic pain
      were not receiving pain relief drugs. The general feeling of illness was lower in
      KTx than HD patients (4.54 +/- 2.1 vs. 5.6 +/- 0.7; p < 0.0001); however, in the
      former group, it was systematically increasing with the time after
      transplantation. CONCLUSIONS: A successful kidney transplantation does not lead
      to a significant reduction in the prevalence of pain when compared to chronic HD
      patients. Pain relief medications are underused in KTx patients.

PMID- 21083765
TI  - Addition of anti-CD25 to thymoglobulin for induction therapy: delayed return of
      peripheral blood CD25-positive population.
AB  - An anti-CD25 monoclonal antibody was added to thymoglobulin for induction therapy
      in simultaneous pancreas/kidney (SPK) recipients. T-cell subsets including CD3
      and CD25 were assessed by flow cytometry analysis in the peripheral blood of SPK
      (n = 88), and for comparison kidney transplant (KT) recipients were assessed. KT
      recipients were treated with daclizumab (anti-CD25) alone (five doses; 1 mg/kg)
      (n = 27) or thymoglobulin alone (4-7 doses; 1 mg/kg) (n = 23). SPK recipients
      received daclizumab (two doses; 1 mg/kg) in addition to thymoglobulin (five
      doses; 1 mg/kg). The return of peripheral blood CD25+ cells was delayed for 45 d
      post-transplantation in the SPK recipients where anti-CD25 was added to
      thymoglobulin, compared to those KT recipients with thymoglobulin alone. This
      strategy may result in reduced allogeneic (donor-specific) T effector cells at
      the time of solid organ transplantation.

PMID- 21083766
TI  - Is it possible to reduce the knee joint compression force during level walking
      with hiking poles?
AB  - Walking with hiking poles has become a popular way of exercising. Walking with
      poles is advocated as a physical activity that significantly reduces the loading
      of the hip, knee and ankle joints. We have previously observed that pole walking
      does not lead to a reduction of the load on the knee joint. However, it is
      unclear whether an increased force transmitted through the poles can reduce the
      load on the knee joint. Thus, the purpose of the present study was to investigate
      if an increased load transmitted through the arms to the poles could reduce the
      knee joint compression force during level walking with poles. We hypothesized
      that an increased pole force would result in a reduction of the knee joint
      compression force. Gait analyses from 10 healthy subjects walking with poles were
      obtained. The pole force was measured simultaneously during the gait analyses.
      The knee joint compression forces were estimated by using a biomechanical knee
      joint model. The results showed that the subjects were able to increase the pole
      force by 2.4 times the normal pole force. However, this did not lead to a
      reduction in the knee joint compressive force and we rejected our hypothesis. In
      conclusion, the use of poles during level walking does not seem to reduce knee
      joint compressive loads. However, it is possible that the use of poles in other
      populations (e.g. osteoarthritis patients) and in terrain would unload the knee
      joint. This should be investigated in the future.

PMID- 21083767
TI  - A conceptual framework of organizational stressors in sport performers.
AB  - In the study reported here, 12 sport performers (six elite and six non-elite)
      were interviewed with regard to organizational-related issues they had
      experienced in preparation for competition. Grounded theory procedures
      facilitated the development of a conceptual framework of organizational stressors
      consisting of five general dimensions: factors intrinsic to the sport, roles in
      the sport organization, sport relationships and interpersonal demands, athletic
      career and performance development issues, and organizational structure and
      climate of the sport. The data indicate that the stressors were encountered
      proportionately more by elite performers (#EPOS=315) than non-elite performers
      (#NPOS=228) with some demands being in common and some unique to each group. The
      results are discussed in relation to previous research and regarding their
      implications for professional practice.

PMID- 21083768
TI  - Validity and responsiveness of the ankle function score after acute ankle injury.
AB  - The purpose of this study was to examine prognostic validity, concurrent validity
      and responsiveness of ankle function score (AFS) for patients with acute ankle
      injury. In a prospective cohort study, AFS was compared with Olerud and Molander
      ankle score (OMAS), patient-specific complaints (PSC), and global perceived
      effect. Sensitivity and specificity were calculated to estimate prognostic
      validity; correlation was calculated for concurrent validity. Effect Size,
      Standardized Response Mean, and Responsiveness Ratio were calculated to estimate
      responsiveness. The sensitivity of AFS was 76% and the specificity was 57%.
      Correlation between AFS and OMAS at baseline, end of treatment and difference was
      0.82, 0.70 and 0.79, respectively. Outcomes for responsiveness of AFS were
      comparable to outcomes for OMAS and PSC. This study found limited evidence for
      the AFS as a prognostic and evaluative instrument. The AFS is a simple instrument
      based on basic functional outcomes (pain, stability, weight bearing, swelling and
      gait) and may be used in addition to subjective clinical judgment as a prognostic
      and evaluative tool for recovery after acute ankle injury.

PMID- 21083770
TI  - Diving reflex: can the time course of heart rate reduction be quantified?
AB  - In this meta-analysis of diving bradycardia in humans, we sought to quantify any
      heart rate (HR) reduction using a relatively simple mathematical function. Using
      the terms "diving reflex,""diving bradycardia,""diving response,""diving plus
      heart rate," databases were searched. Data from the studies were fitted using
      HR=c+aexp(-(t-t(0))/tau), where c is the final HR, a is the HR decrease, tau is
      the time constant of HR decay, and t(0) is the time delay. Of 890 studies, 220
      were given closer scrutiny. Only eight of these provided data obtained under
      comparable conditions. Apneic facial immersion decreased HR with tau=10.4 s and
      in air alone it was less pronounced and slower (tau=16.2 s). The exponential
      function fitted the time course of HR decrease closely (r(2)>0.93). The fit was
      less adequate for apneic-exercising volunteers. During apnea both with and
      without face immersion, HR decreases along a monoexponential function with a
      characteristic time constant. HR decrease during exercise with and without face
      immersion could not readily be described with a simple function: the
      parasympathetic reaction was partially offset by some sympathetic activity. Thus,
      we succeeded in quantifying the early time course of diving bradycardia. It is
      concluded that the diving reflex is useful to diagnose the integrity of efferent
      cardiovascular autonomic pathways.

PMID- 21083769
TI  - Antioxidant effect of lemon verbena extracts in lymphocytes of university
      students performing aerobic training program.
AB  - Aerobic training is related to an increase in blood oxidation markers. The
      purpose of the present study was to investigate the antioxidant capacity of
      Lippia citriodora extracts (PLX((r)) ) on plasma and blood cell oxidative status
      of university students beginning a 21 days aerobic training routine (3
      days/week). Using a double-blind design, 15 male athletes (21 +/- 2.1 years) were
      assigned to a group consuming 1.8 g/day of the plant extract (PLX((r)) -group) or
      a placebo (PLB-group). Two blood extractions were performed at day 0 and 21, from
      which lymphocytes, erythrocytes and plasma were isolated. Several circulating
      parameters, antioxidant enzyme activities and oxidative stress markers were
      measured. The PLX((r)) -group displayed an increased HDL-cholesterol, a modest
      decrease in erythrocyte number and an increased circulating urea. Activation of
      glutathione (GSH)-reductase was observed in erythrocytes and lymphocytes of
      PLX((r)) -group, accompanied by lower levels of oxidative stress markers, such as
      malondialdehyde and protein carbonyls in plasma. The antioxidant action exerted
      by PLX((r)) on GSH-reductase seems to be post-translational and mainly due to
      verbascoside, a phenylpropanoid that represents 10% (w/w) of extract content. In
      conclusion, PLX((r)) shows antioxidant properties that could play an important
      role in modulating GSH-reductase activity in lymphocytes and erythrocytes and
      protecting plasma from exercise oxidative damage.

PMID- 21083771
TI  - High-dose inhaled salbutamol has no acute effects on aerobic capacity or oxygen
      uptake kinetics in healthy trained men.
AB  - The prevalence of asthma is higher among elite athletes than in the general
      population. This has resulted in the frequent use of anti-asthmatic medication
      such as beta2-agonists among asthmatic athletes. Beta2-agonists are on the
      prohibited list of WADA. The use of the beta2-agonist salbutamol is only
      permitted in therapeutic inhaled doses. Most studies have reported the lack of
      ergogenic effects of therapeutic doses of inhaled beta2-agonists measured in
      maximal oxygen uptake. No previous studies have examined any possible effects of
      high-dose inhaled salbutamol on oxygen uptake kinetics. We enrolled nine healthy
      well-trained men in a randomized, blinded, placebo-controlled crossover study.
      Subjects were randomized to inhalation of 40 puffs of 0.2 mg salbutamol or two
      placebo tablets and performed an incremental test to exhaustion and three
      submaximal tests at 75% of peak power to determine oxygen uptake kinetics. During
      the incremental test, there were no effects of inhaled salbutamol on VO(2max) in
      absolute or relative terms, and no effect on peak power and lactate threshold.
      During the submaximal test, we found no effects on the time constant, time delay,
      the mean response time or O(2) deficit related to oxygen uptake kinetics. In
      conclusion, no ergogenic effect of a high dose of salbutamol on aerobic capacity
      was found.

PMID- 21083772
TI  - Small bowel preservation for intestinal transplantation: a review.
AB  - Intestinal transplantation has become the therapy of choice for patients with
      intestinal failure and life-threatening complications from total parenteral
      nutrition. Results, however, remain inferior as compared with other transplant
      types with the quality of the organ graft as the most important factor of outcome
      after transplantation. The intestine is extremely sensitive to ischemia.
      Unfortunately, a relatively long ischemic preservation period is inevitable. The
      current standard in organ preservation [cold storage (CS) with University of
      Wisconsin solution] was developed for kidney/liver preservation and is suboptimal
      for the intestinal graft despite good results for other organs. This review aimed
      at appraising the results from the use of previously applied and recently
      developed preservation solutions and techniques to identify key areas for
      improvement. As the studies available do not reveal the most effective method for
      intestinal preservation, an optimal strategy will result from a synergistic
      effect of different vital elements identified from a review of published material
      from the literature. A key factor is the composition of the solution using a low
      viscosity solution to facilitate washout of blood, including amino acids to
      improve viability, impermeants and colloids to prevent edema, and buffer for pH
      homeostasis. Optimizing conditions include a vascular flush before CS and luminal
      preservation. The most effective composition of the luminal solution and a
      practical, clinically applicable optimal technique are yet to reach finality.
      Short-duration oxygenated arterial and/or luminal perfusion have to be
      considered. Thus, a tailor-made approach to luminal preservation solution and
      technique need further investigation in transplant models and the human setting
      to develop the ultimate technique meeting the physiologic demands of the
      intestinal graft during preservation.

PMID- 21083773
TI  - Follicular progesterone levels decrease during the period of seasonal infertility
      in sows.
AB  - Impaired reproductive performance exhibited by the domestic sow during the late
      summer and early autumn months is referred to as seasonal infertility. This study
      was carried out to determine whether there are changes in ovarian morphology and
      follicular steroidogenesis associated with season, which may be associated with
      seasonal infertility. Ovaries were collected in pairs from sows sourced from two
      farms and slaughtered 4 days after weaning during winter and summer. The mean
      progesterone concentration in follicular fluid (FF) collected from small
      follicles was lower in summer (701.3 +/- 115.54 nm) compared with winter (1235.55
      +/- 164.47 nm; p<0.001). The mean progesterone concentration in the FF of large
      follicles was also lower in summer (1469.2 +/- 156.51 nm) compared with winter
      (2470.9 +/- 169.13 nm; p<0.001). The number of large surface antral follicles (5
      8 mm in diameter) on the ovaries recovered from Farm A sows was higher during
      summer (17.76 +/- 0.56) than in winter (15.38 +/- 0.54; p<0.05). Similarly, the
      number of small follicles (3-4 mm in diameter) on Farm A sow ovaries was higher
      in summer (8.46 +/- 0.66) than in winter (4.63 +/- 0.53; p<0.001). In contrast,
      the number of small follicles on the surface of ovaries recovered from Farm B
      sows was higher during winter (10.17 +/- 1.50) than in summer (6.45 +/- 1.00;
      p<0.01). The number of pre-ovulatory follicles (>8 mm in diameter) was also
      higher in winter (1.23 +/- 1.68) when compared to summer (0.51 +/- 0.3; p<0.001)
      on the ovaries of sows from Farm B. The results suggest that there are seasonal
      differences in follicular steroidogenesis and ovarian dynamics. These findings
      add support to the theory that altered follicular steroidogenesis and ovarian
      morphology may possibly be the mechanism behind reduced reproductive performance
      during the period of seasonal infertility in sows.

PMID- 21083774
TI  - Synchronised expressions of LPXRFamide peptide and its receptor genes: seasonal,
      diurnal and circadian changes during spawning period in grass puffer.
AB  - Among the RFamide peptide family, the LPXRFamide peptide (LPXRFa) group regulates
      the release of various pituitary hormones and, recently, LPXRFa genes were found
      to be regulated by photoperiod via melatonin. As a first step towards
      investigating the role of LPXRFa on reproductive function in grass puffer
      (Takifugu niphobles), which spawns in semilunar cycles, genes encoding LPXRFa and
      its receptor (LPXRFa-R) were cloned, and seasonal, diurnal and circadian changes
      in their absolute amounts of mRNAs in the brain and pituitary were examined by
      quantitative real-time polymerase chain reaction. The grass puffer LPXRFa
      precursor contains two putative RFamide peptides and one possible RYamide
      peptide. LPXRFa and LPXRFa-R genes were extensively expressed in the diencephalon
      and pituitary. The expression levels of both genes were significantly elevated
      during the spawning periods in both sexes in the brain and pituitary, although
      they were low in the spawning fish just after releasing eggs and sperm. The
      treatment of primary pituitary cultures with goldfish LPXRFa increased the
      amounts of follicle-stimulating hormone beta- and luteinising hormone beta
      subunit mRNAs. In the diencephalon, LPXRFa and LPXRFa-R genes showed synchronised
      diurnal and circadian variations with one peak at zeitgeber time 3 and circadian
      time 15, respectively. The correlated expression patterns of LPXRFa and LPXRFa-R
      genes in the diencephalon and pituitary and the possible stimulatory effects of
      LPXRFa on gonadotrophin subunit gene expression suggest the functional
      significance of the LPXRFa and LPXRFa-R system in the regulation of lunar
      synchronised spawning of grass puffer.

PMID- 21083777
TI  - Guest editorial: Lead us not again: clinical leadership and the disciplinary
      contribution.

PMID- 21083775
TI  - The performance of a component-based allergen microarray for the diagnosis of
      kiwifruit allergy.
AB  - BACKGROUND: Allergy to kiwifruit is increasingly reported across Europe.
      Currently, the reliability of its diagnosis by the measurement of allergen
      specific IgE with extracts or by skin testing with fresh fruits is unsatisfying.
      OBJECTIVE: To evaluate the usefulness of a component-based allergen microarray
      for the diagnosis of kiwifruit allergy in a large group of patients. METHODS:
      With an allergen microarray, we measured specific IgE and IgG4 levels to a panel
      of nine kiwifruit allergens in sera of 237 individuals with kiwifruit allergy.
      Sera from 198 allergic patients without kiwifruit allergy served as controls.
      Furthermore, we determined the extent of sensitization to latex. RESULTS: The
      panel of kiwifruit allergens showed a diagnostic sensitivity of 66%, a
      specificity of 56% and a positive predictive value of 73%. Sera from kiwifruit
      allergic patients contained significantly more frequently Act d 1-specific IgE
      than sera from control patients. Furthermore, 51% of the positive sera contained
      IgE directed to a single allergen, namely Act d 1 (45%), Act d 9 (27%) or Act d 7
      (13%). Within the control group, 36% sera recognized a single allergen. Out of
      those, 48% were positive to the cross-reactive glycoallergen Act d 7, 43% to the
      profilin Act d 9 and only 5% to Act d 1. Allergen-specific IgG4 levels did not
      differ between kiwifruit-allergic and -tolerant patients. Kiwifruit- and latex
      allergic patients contained Hev b 11-specific IgE significantly more frequently
      than latex-allergic patients without kiwifruit allergy. CONCLUSIONS: Act d 1 can
      be considered a marker allergen for genuine sensitization to kiwifruit. We
      demonstrated that a component-based kiwifruit allergen microarray would improve
      the prognostic value of in vitro diagnostic tests.

PMID- 21083776
TI  - Clinical and serological diagnoses of a patient with vancomycin-induced
      thrombocytopenia.

PMID- 21083779
TI  - The National Expert Standard Pressure Ulcer Prevention in Nursing and pressure
      ulcer prevalence in German health care facilities: a multilevel analysis.
AB  - AIMS AND OBJECTIVES: The objective of this study was to describe the relationship
      between the German National Expert Standard Pressure Ulcer Prevention and the
      pressure ulcer prevalence in German nursing homes and hospitals. BACKGROUND: The
      patient outcome pressure ulcer does not only depend on individual characteristics
      of patients, but also on institutional factors. In Germany, National Expert
      Standards are evidence-based instruments that build the basis of continuing
      improvement in health care quality. It is expected that after having implemented
      the National Expert Standard Pressure Ulcer Prevention, the number of pressure
      ulcers should decrease in health care institutions. DESIGN: The analysed data
      were obtained from two cross-sectional studies from 2004-2005. METHODS: A
      multilevel analysis was performed to show the impact of the National Expert
      Standard Pressure Ulcer Prevention on pressure ulcer prevalence. RESULTS: A total
      of 41.5% of hospitals and 38.8% of the nursing homes claimed to use the National
      Expert Standard in the process of developing their local protocols. The overall
      pressure ulcer prevalence grade 2-4 was 4.7%. Adjusted for hospital departments,
      survey year and individual characteristics, there was no significant difference
      in the prevalence of pressure ulcers between institutions that refer to the
      National Expert Standard or those referring to other sources in developing their
      local protocols (OR=1.14, 95% CI=0.90-1.44). CONCLUSIONS: There was no empirical
      evidence demonstrating that local protocols of pressure ulcer prevention based on
      the National Expert Standard were superior to local protocols which refer other
      sources of knowledge with regard to the pressure ulcer prevalence. RELEVANCE TO
      CLINICAL PRACTICE: The use of the National Expert Standard Pressure Ulcer
      Prevention can neither be recommended nor be refused. The recent definition of
      implementation of Expert Standards should be mandatory for all health care
      institutions which introduce Expert Standards.

PMID- 21083778
TI  - A systematic review of therapeutic interventions for poststroke depression and
      the role of nurses.
AB  - AIMS AND OBJECTIVES: This systematic review explores the nursing role in the
      management of poststroke depression and identifies effective non-pharmacological
      interventions that nurses can use in the daily care of patients with stroke.
      BACKGROUND: Depression is a common complication poststroke and affects one-third
      of patients with stroke. It has a negative impact on functional recovery and
      social activities and is associated with increased morbidity and mortality.
      Detection and diagnosis of poststroke depression is inconsistent, and many
      depressed patients are under-treated. Although nurses recognise that observation
      and assessment are parts of their role in rehabilitation care, little is known
      about their role in assessing depression or the interventions they can use.
      DESIGN: A systematic review was conducted using the Cochrane method. METHODS:
      Literature for the period 1993-2008 was searched in the electronic databases of
      CINAHL, Medline (PubMed), Nursing Journals (PubMed) and PsycINFO using the
      following keywords: cerebrovascular accident, stroke, depression, poststroke
      depression, treatment, therapy, treatment outcome, management. RESULTS: Fifteen
      articles and one systematic review were identified. There was strong evidence
      that information provision reduces the severity of depression. Other
      interventions with positive effects on the occurrence or severity of poststroke
      depression were as follows: life review therapy, motivational interviewing, a
      specific nursing support programme and physical exercise. CONCLUSION: Depression
      after stroke is an important problem with adverse effects on the patient's
      ability to participate in rehabilitation and on rehabilitation outcome. The
      interventions described can be implemented in nursing care of patients with
      poststroke depression. The variety of such interventions and the diversity of
      their nature and design are consistent with the practice of rehabilitation
      nursing. RELEVANCE TO CLINICAL PRACTICE:   The findings of this review enable
      nurses to intervene effectively to reduce the occurrence and severity of
      depression in patients with stroke.

PMID- 21083780
TI  - An historical perspective on the treatment of vocation in the Briggs Report
      (1972).
AB  - AIMS AND OBJECTIVES: To examine the vocational ideal in the Briggs Report (Briggs
      1972), its evidence, context and interpretation. BACKGROUND: As recently argued
      in Journal of Clinical Nursing, twentieth century reports have misrepresented
      nursing. This paper considers this argument in relation to the Briggs Report and
      its understanding of vocation. DESIGN: Sources consulted: nursing periodicals
      1960-1975, nursing textbooks 1937-1971, the Briggs Report, research studies on
      nursing 1961-1971, secondary works on nursing history. Included are three newly
      discovered major primary sources. METHODS: An historiographical analysis of
      archival sources which interrogates primary and secondary evidence to make
      transparent interconnection, coherence, consistency and reliability. RESULTS:
      Despite evidence from its own commissioned data that vocation was an important
      motivating factor, the Briggs Report recommended a new nursing model. CONCLUSION:
      The concept of vocation in nursing has been commonly interpreted as a cultural
      tool hindering the subsequent development of nursing. This approach has been a
      driver for policy decisions in nursing. Despite its own evidence, the Briggs
      Committee recommended far reaching changes, accepted by government and
      implemented over the following decade as Project 2000. The concept of vocation
      warrants further scholarship. RELEVANCE TO CLINICAL PRACTICE: Whether the
      historical ideal of vocation remains important, negatively or positively, to the
      attitudes, values and motivations of the clinical nurse and the quality of
      patient care, is a relevant and significant issue for contemporary UK and
      international nursing practice and policy.

PMID- 21083781
TI  - Workloads of Parkinson's specialist nurses: implications for implementing
      national service guidelines in England.

PMID- 21083782
TI  - Effect of Fowler's body position on blood pressure measurement.

PMID- 21083783
TI  - A survey of nurses' perceived barriers to research utilisation in Hong Kong.

PMID- 21083784
TI  - The role of midwives and health visitors in promoting intergenerational language
      maintenance in the bilingual setting: perceptions of parents and health
      professionals.
AB  - AIMS AND OBJECTIVES: The increasing status and regard of indigenous minority
      languages across Europe, means the advantages of bilingualism for individuals and
      communities are now well established. We set out to elicit parents' and health
      professionals' views of the role of health visitors and midwives in promoting
      bilingualism in the family and to consider whether health professionals
      acknowledge the contribution that bilingualism makes to public health.
      BACKGROUND: A three-year study was completed to measure the impact of a language
      transmission initiative which depends on the input of midwives and health
      visitors with new parents and how its effect could be improved. This paper
      reports on one element of that study. DESIGN: A qualitative approach was used.
      METHODS: Six focus group interviews were conducted with health visitors and
      midwives and 33 postnatal interviews were completed with parents across four
      counties in Wales. Thematic content analysis was undertaken by two researchers, a
      third trailed decision processes and scrutinised categories and themes. RESULTS:
      Findings suggest that health visitors and midwives perceive their roles relating
      to the promotion of bilingualism differently. Influences on their involvement
      include their language profile, contact with parents, personal experience, timing
      of the interaction and time in their workload. The relationship between promoting
      bilingualism and public health was accepted by some and denied by others. Data
      from the interviews with parents suggested that few health professionals discuss
      issues of language transmission with new parents. CONCLUSIONS: Some individual
      health visitors and midwives are willing to promote bilingualism with parents.
      However, there are challenges in enlisting the support of health visitors and
      midwives to discuss language transmission and bilingualism with parents.
      RELEVANCE TO CLINICAL PRACTICE: These findings challenge practitioners to
      consider their role in promoting bilingualism and its effect on public health and
      suggest the need for more defined responsibilities.

PMID- 21083785
TI  - Working condition of nurses in Japan: awareness of work-life balance among
      nursing personnel at a university hospital.
AB  - AIM: The aim of this study was to examine the awareness of work-life balance
      (WLB) among the nursing personnel at a university hospital in Japan. DESIGN:
      Survey. METHODS: A questionnaire was sent to 1236 nursing personnel working at a
      university hospital and 1081 (87.5%) responses received. The questions concerned
      the following: (1) respondent demographical characteristics, (2) living
      background, (3) wishes for working environments and (4) motivation to work and
      health condition. The data were analysed by simple and cross-tabulations.
      RESULTS: The results can be summarised as follows: (1) the concept and
      significance of WLB has not yet been established among nurses in Japan, (2) three
      factors were found, which nurses need as working environment, 1st quality-of-life
      benefits, 2nd flexible working style, 3rd lifelong learning and (3) nurses who
      reported good WLB also reported higher job satisfaction and job motivation.
      CONCLUSION: The concept and significance of WLB has not yet been established
      among nurses. Thus, it is needed to enlighten nurses on the concept and
      significance of WLB as well as how they should practise WLB. Approximately half
      of the nurses gave their jobs first priority in reality, although they had
      various needs for their private lives and household affairs, as well as jobs. WLB
      cannot be achieved only by individual attitudes; thus, organisational efforts are
      necessary. In the correlation between WLB and 'job satisfaction' and 'job
      motivation,' nurses who were satisfied with their job and those who were highly
      motivated showed higher WLB. There was a significant correlation between
      satisfaction and motivation. RELEVANCE TO CLINICAL PRACTICE: It is necessary that
      nurses understand and have any information about working policy to improve
      working conditions to get better conditions which they need.

PMID- 21083786
TI  - Lower extremity ulcer management: best practice algorithm.
AB  - AIMS AND OBJECTIVES: This literature review aims to define best nursing practice
      for lower limb ulcer care promoting stabilisation of this physiological
      consequence of diabetes mellitus and to help provide improved integration of
      health-within-illness for the patients. BACKGROUND: According to the Centers of
      Disease Control, the number of people with diabetes has risen from 20.8 million
      in 2005 to over 23.6 million in 2007. Research has identified best practice
      algorithms for care of the diabetic foot, yet none for the ulcerations on the
      limb from the knee to the ankle. DESIGN: The design of this literature review is
      to compile research from both nursing and medical communities to develop a best
      practice for the stabilisation of a lower limb ulcer. A literature search was
      conducted based on the theoretical framework of stabilisation of a chronic
      condition. METHODS: Twenty-nine articles were identified for use in the
      evaluation of best practice of lower limb ulcerations. Each article was
      synthesised using a protocol tool. RESULTS: Control of hyperglycaemia, infection
      control, ulcer debridement, use of dressings and compression therapy to relieve
      venous congestion were all identified as important factors in the treatment of
      lower limb ulcerations. CONCLUSIONS: This systematic literature review has
      resulted in a 'best nursing practice algorithm' for the stabilisation and care of
      lower limb ulcerations regardless of underlying cause. This care algorithm could
      be used in collaboration with other health care providers to promote
      stabilisation of lower limb ulcers and improve the overall quality of life of
      patient cohort. RELEVANCE TO CLINICAL PRACTICE: The results of this study yield a
      suggested 'best practice' algorithm for the stabilisation of a lower limb ulcer-
      treat and control hyperglycaemia; prevent and/or control infection of the ulcer;
      routine debridement of the ulcer; using the most appropriate type of dressings
      for each patient; and the application of compression therapy. This algorithm can
      also be used for to frame patient teaching regarding appropriate treatments and
      therapies to promote the patient's self-care and stabilisation of the ulcer.

PMID- 21083787
TI  - Propofol and children--what we know and what we do not know.
AB  - The pharmacokinetics of propofol are relatively well described in the pediatric
      population. Recent work has confirmed the validity of allometric scaling for
      predicting propofol disposition across different species and for describing
      pediatric ontogenesis. In the first year of life, allometric models require
      adjustment to reflect ontogeny of maturation. Pharmacodynamic data for propofol
      in children are scarcer, because of practical difficulties in data collection and
      the limitations of currently available depth of anesthesia monitors for pediatric
      use. Hence, questions relating to the comparative sensitivity of children to
      propofol, and differences in time to peak effect relative to adults, remain
      unanswered. K(eo) half-lives have been determined for pediatric kinetic models
      using time to peak effect techniques but are not currently incorporated into
      commercially available target-controlled infusion pumps.

PMID- 21083788
TI  - Dual roles of a variable number of tandem repeat polymorphism in the TERT gene in
      lung cancer.
AB  - This study was conducted to determine the impact of a functional tandem repeat
      minisatellite (MNS16A) polymorphism in the telomerase reverse transcriptase
      (TERT) gene on the risk of lung cancer, as well as on survival of patients with
      non-small-cell lung cancer (NSCLC). The effect of the MNS16A variable number of
      tandem repeat (VNTR) polymorphism on the risk of lung cancer was evaluated in a
      case-control study that consisted of 937 lung cancer patients and 943 healthy
      controls. The effect of the polymorphism on survival outcome was evaluated in 703
      patients with surgically resected NSCLC. Compared with the VNTR-302 allele, the
      VNTR-243 allele was associated with a significantly increased risk of lung cancer
      (adjusted odds ratio, 1.55; 95% confidence interval [CI], 1.07-2.25; P = 0.02).
      In addition, the genotypes carrying at least one VNTR-243 allele were associated
      with a significantly increased risk of lung cancer compared with the genotypes
      with no VNTR-243 allele (adjusted odds ratio, 1.61; 95% CI, 1.09-2.38; P = 0.02).
      In contrast to the effect of the polymorphism on the risk of lung cancer, the
      genotypes carrying at least one VNTR-243 allele were associated with a
      significantly better overall survival in patients with surgically resected NSCLC
      (adjusted hazard ratio, 0.51; 95% CI, 0.28-0.93; P = 0.03). These findings
      suggest that the MNS16A VNTR polymorphism in the TERT gene has dual, conflicting
      roles in lung carcinogenesis. This polymorphism may increase the risk of lung
      cancer development, and may improve survival in lung cancer patients.

PMID- 21083789
TI  - Swallow induces a peristaltic wave of distension that marches in front of the
      peristaltic wave of contraction.
AB  - BACKGROUND: Current understanding is that swallow induces simultaneous inhibition
      of the entire esophagus followed by a sequential wave of contraction
      (peristalsis). We observed a pattern of luminal distension preceding contraction
      which suggested that inhibition may also traverses in a peristaltic fashion. Our
      aim is to determine the relationship between contraction and luminal distension
      during bolus transport. METHODS: Eight subjects using two solid-state pressure
      and two ultrasound (US) transducers were studied. Synchronous pressure and US
      images were obtained with wet swallows and after edrophonium and atropine.
      Luminal cross-sectional area (CSA) at 2 cm and 12 cm above the lower esophageal
      sphincter (LES) were recorded. Relationship between pressure and CSA at each
      site, propagation velocity of peak pressure and peak distension waves were
      determined. Fluoroscopy coupled with manometry was also performed in five normal
      subjects. KEY RESULTS: Esophageal distension precedes contraction wave at both
      recorded sites. During distension, esophageal pressure remains constant while
      luminal CSA increases significantly. The onset and the peak of distension wave
      traverses in a peristaltic fashion between both sites. A tight coupling exists
      between the peak distension and peak contraction waves with similar velocities
      (3.7 cm s(-1) and 3.6 cm s(-1)) of propagation. The degree of distension is
      greater at 2 cm compared to 12 cm. Atropine and edrophonium reduced and increased
      the contraction pressure respectively, without affecting the distension wave.
      Fluoroscopic study confirmed that the wave of distension traverses the esophagus
      in a peristaltic fashion. CONCLUSIONS & INFERENCES: Distension and contraction
      waves are tightly coupled to each other and both traverse in a peristaltic
      fashion.

PMID- 21083790
TI  - Valganciclovir is an effective prophylaxis for cytomegalovirus disease in liver
      transplant recipients.
AB  - OBJECTIVES: Cytomegalovirus (CMV) infection is responsible for significant
      morbidity and mortality among solid organ transplant recipients. Prophylaxis
      using valganciclovir (VGCV) in orthotopic liver transplant (OLT) recipients is
      not approved by the Food and Drug Administration and its use is controversial.
      This study aimed to evaluate the effectiveness of VGCV in CMV prophylaxis in OLT
      recipients. METHODS: We carried out a retrospective, single-centre study
      including all OLT procedures performed during 2005-2008. Patients with early
      death (at <= 30 days), without CMV serology or prophylaxis, or with follow-up of
      <1 year were excluded. RESULTS: The overall incidence of CMV disease was 6% (n=
      9). The ganciclovir (GCV) and VGCV groups had similar incidences of CMV disease
      (4.6% vs. 7.0%; P= 0.4) and similar distributions of disease presentation (CMV
      syndrome vs. tissue-invasive CMV; P= 0.4). Incidences of CMV infection, as well
      as disease presentation, were similar between the high-risk (CMV D+/R-) and non
      high-risk groups (P= 0.16). Although acute cellular rejection occurred more
      frequently in patients who developed CMV disease (P= 0.005), overall survival in
      these patients did not differ from that in patients who did not develop CMV
      infection (P= 0.5). CONCLUSIONS: Valganciclovir is an effective antiviral for the
      prevention of CMV disease in liver transplant recipients. Our data support its
      use in high-risk OLT patients.

PMID- 21083791
TI  - Segmental cholangitis impairs hepatic regeneration capacity after partial
      hepatectomy in rats.
AB  - BACKGROUND: Patients with hilar cholangiocarcinoma or hepatolithiasis often
      develop segmental cholangitis (SC), but it is unclear whether hepatectomy for
      patients with SC can be performed safely. METHODS: Rats were subjected to
      segmental bile duct ligation (SBDL) with LPS (SC group) or a saline (Sham group)
      infusion into the bile duct of the ligated lobes. The rats were sacrificed at 3,
      24 and 48 h after the SBDL. For another experiment, the rats were subjected to
      partial hepatectomy (PHx) for the ligated lobes. Hepatic regeneration rates and
      the expression of regeneration-associated genes were evaluated. RESULTS: In the
      SC group, severe parenchymal damage was observed in the acute phase (3 h).
      Altered gene expression in the liver in response to biliary infection occurred
      not only in the infected lobes but also in the non-infected lobes. In the rats of
      the SC group, both the hepatic regeneration rate and serum HGF levels were
      significantly lower than in the Sham group. CONCLUSION: These results clearly
      demonstrate that SC impairs the regeneration capacity of the contralateral
      remnant liver. Therefore, hepatectomy should be avoided for patients with SC even
      if it occurs in the part of the liver to be resected.

PMID- 21083792
TI  - T cell infiltrate and outcome following resection of intermediate-grade primary
      neuroendocrine tumours and liver metastases.
AB  - BACKGROUND: Tumour-infiltrating lymphocytes (TILs) have been shown to predict
      survival in numerous malignancies. The importance of TILs in primary pancreatic
      neuroendocrine tumours (NETs) and NET liver metastases (NETLMs) has not been
      defined. METHODS: We identified 87 patients with NETs and 39 with NETLMs who had
      undergone resection. Immunohistochemistry was performed to determine TIL counts.
      Recurrence-free survival (RFS) and overall survival (OS) were determined using
      the log-rank test. RESULTS: The median follow-up time was 62 months in NET
      patients and 48 months in NETLM patients. Vascular invasion and histologic grade
      were the only independent predictors of outcome for NETs and NETLMs,
      respectively. Analysis of intermediate-grade NETs indicated that a dense T cell
      (CD3+) infiltrate was associated with a median RFS of 128 months compared with 61
      months for those with low levels of intratumoral T cells (P= 0.05, univariate
      analysis). Examination of NETLMs revealed that a low level of infiltrating
      regulatory T cells (Treg, FoxP3+) was a predictor of prolonged survival (P <
      0.01, univariate analysis). CONCLUSIONS: A robust T cell infiltrate is associated
      with improved RFS following resection of intermediate-grade NETs, whereas the
      presence of more Treg correlated with shorter OS after treatment of NETLMs.
      Further study of the immune response to intermediate-grade NETs and NETLMs is
      warranted.

PMID- 21083793
TI  - Is there any difference between right hepatectomy and left lateral sectionectomy
      for living donors? as much you cut, as much you hurt?
AB  - BACKGROUND: The worldwide rising demand for cadaveric donors in liver
      transplantation is an important incentive for the development of alternative
      transplantation options, such as living donors. A precise evaluation of surgical
      complications is, therefore, considered to be an important issue in this setting.
      AIM: Present a retrospective analysis of 126 living donors hepatectomies
      undertaken at our centre. METHODS: From December 2002 to August 2009, 126 living
      donors were submitted to hepatectomy. Donors' complications were stratified
      according to Clavien's scoring system to compare the morbidity of right
      hepatectomy (RH) (Group 1) and left lateral sectionectomy (LLS) (Group 2).
      RESULTS: Thirty-nine complications were observed in 35 patients. Sixty LLS, 3
      left (LH) and 63 RH were performed. The complications were classified as: Clavien
      grade 1-11 (28.2%), grade 2-12 (30.7%), grade 3A-13 (33.3%), grade 3B-2 (5.1%)
      and grade 4A-1 (2.5%). When Group 1 (63 patients) and Group 2 (60 patients) were
      compared, there was no significant difference between the number of
      complications: 20 (31%) and 14 (23%), respectively (P > 0.3). CONCLUSIONS:
      Hepatectomy for living donor liver transplantation (LDLT) was a safe procedure,
      regardless of the type of liver resection undertaken. We found no difference in
      morbidity between RH and LLS, which suggests that complications may occur despite
      the amount of liver retrieved.

PMID- 21083794
TI  - Natural language processing for the development of a clinical registry: a
      validation study in intraductal papillary mucinous neoplasms.
AB  - BACKGROUND: Medical natural language processing (NLP) systems have been developed
      to identify, extract and encode information within clinical narrative text.
      However, the role of NLP in clinical research and patient care remains limited.
      Pancreatic cysts are common. Some pancreatic cysts, such as intraductal papillary
      mucinous neoplasms (IPMNs), have malignant potential and require extended periods
      of surveillance. We seek to develop a novel NLP system that could be applied in
      our clinical network to develop a functional registry of IPMN patients.
      OBJECTIVES: This study aims to validate the accuracy of our novel NLP system in
      the identification of surgical patients with pathologically confirmed IPMN in
      comparison with our pre-existing manually created surgical database (standard
      reference). METHODS: The Regenstrief EXtraction Tool (REX) was used to extract
      pancreatic cyst patient data from medical text files from Indiana University
      Health. The system was assessed periodically by direct sampling and review of
      medical records. Results were compared with the standard reference. RESULTS:
      Natural language processing detected 5694 unique patients with pancreas cysts, in
      215 of whom surgical pathology had confirmed IPMN. The NLP software identified
      all but seven patients present in the surgical database and identified an
      additional 37 IPMN patients not previously included in the surgical database.
      Using the standard reference, the sensitivity of the NLP program was 97.5% (95%
      confidence interval [CI] 94.8-98.9%) and its positive predictive value was 95.5%
      (95% CI 92.3-97.5%). CONCLUSIONS: Natural language processing is a reliable and
      accurate method for identifying selected patient cohorts and may facilitate the
      identification and follow-up of patients with IPMN.

PMID- 21083795
TI  - A simple scoring system based on clinical factors related to pancreatic texture
      predicts postoperative pancreatic fistula preoperatively.
AB  - BACKGROUND: Postoperative pancreatic fistula (POPF) is regarded as the most
      serious complication of pancreatic surgery. The preoperative risk stratification
      of patients by simple means is of interest in perioperative clinical management.
      METHODS: Based on prospective data, we performed a risk factor analysis for POPF
      after pancreatoduodenectomy in 62 patients operated between 2006 and 2008 with
      special focus on clinical parameters that might serve to predict POPF. A
      predictive score was developed and validated in an independent second dataset of
      279 patients operated between 2001 and 2010. RESULTS: Several pre- and
      intraoperative factors, as well as underlying pathology, showed significant
      univariate correlation with rate of POPF. Multivariate analysis (binary logistic
      regression) disclosed soft pancreatic texture (odds ratio [OR] 10.80, 95%
      confidence interval [CI] 1.80-62.20) and history of weight loss (OR 0.15, 95% CI
      0.04-0.66) to be the only independent preoperative clinical factors influencing
      POPF rate. The subjective assessment of pancreatic hardness by the surgeon
      correlated highly with objective assessment of pancreatic fibrosis by the
      pathologist (r = -0.68, P < 0.001, two-tailed Spearman's rank correlation). A
      simple risk score based on preoperatively available clinical parameters was able
      to stratify patients correctly into three risk groups and was independently
      validated. CONCLUSIONS: Preoperative stratification of patients regarding risk
      for POPF by simple clinical parameters is feasible. Pancreatic texture, as
      evaluated intraoperatively by the surgeon, is the strongest single predictive
      factor of POPF. The findings of the study may have important implications for
      perioperative risk assessment and patient care, as well as for the choice of
      anastomotic techniques.

PMID- 21083796
TI  - An evaluation of electrosurgical vessel-sealing devices in biliary tract surgery
      in a porcine model.
AB  - OBJECTIVES: The purpose of this study was to evaluate two electrosurgical vessel
      sealing devices in biliary surgery. METHODS: Porcine common bile ducts (CBDs)
      were sealed with two electrosurgical devices, an electrothermal bipolar vessel
      sealing device (EBVS) and ultrasonic coagulation shears. Acute study animals
      underwent surgical bile duct sealing followed by immediate burst pressure
      testing. Chronic study animals were maintained for 1 week postoperatively and
      then tested. RESULTS: The seal failure rate in the acute study was 50% for both
      the EBVS device and shears, and 0% for the laparoscopic surgical clip device used
      as a control. The latter had significantly higher burst pressures (646.2 +/-
      281.8 mmHg; P = 0.006) than the EBVS device (97.6 +/- 86.6 mmHg) and shears (71.7
      +/- 89.3 mmHg). No significant difference in burst pressures was noted between
      the EBVS device and shears (97.6 +/- 86.6 mmHg vs. 71.7 +/- 89.3 mmHg). In the
      chronic study, obvious bile leaks occurred in one of four pigs (25%) in the EBVS
      device subgroup and two of four pigs (50%) in the shears subgroup. The average
      proximal CBD pressure in seven pigs was 16.1 +/- 4.1 mmHg. The average chronic
      burst pressure in the control subgroup was 1088.0 +/- 922.6 mmHg. CONCLUSIONS:
      Given the high rates of failure of the EBVS device and the shears in consistently
      sealing biliary ducts, we do not recommend their routine use in biliary surgery.

PMID- 21083797
TI  - Novel 3-D laparoscopic magnetic ultrasound image guidance for lesion targeting.
AB  - OBJECTIVES: Accurate laparoscopic liver lesion targeting for biopsy or ablation
      depends on the ability to merge laparoscopic and ultrasound images with
      proprioceptive instrument positioning, a skill that can be acquired only through
      extensive experience. The aim of this study was to determine whether using
      magnetic positional tracking to provide three-dimensional, real-time guidance
      improves accuracy during laparoscopic needle placement. METHODS: Magnetic sensors
      were embedded into a needle and laparoscopic ultrasound transducer. These sensors
      interrupted the magnetic fields produced by an electromagnetic field generator,
      allowing for real-time, 3-D guidance on a stereoscopic monitor. Targets measuring
      5 mm were embedded 3-5 cm deep in agar and placed inside a laparoscopic trainer
      box. Two novices (a college student and an intern) and two experts
      (hepatopancreatobiliary surgeons) targeted the lesions out of the ultrasound
      plane using either traditional or 3-D guidance. RESULTS: Each subject targeted 22
      lesions, 11 with traditional and 11 with the novel guidance (n= 88). Hit rates of
      32% (14/44) and 100% (44/44) were observed with the traditional approach and the
      3-D magnetic guidance approach, respectively. The novices were essentially unable
      to hit the targets using the traditional approach, but did not miss using the
      novel system. The hit rate of experts improved from 59% (13/22) to 100% (22/22)
      (P < 0.0001). CONCLUSIONS: The novel magnetic 3-D laparoscopic ultrasound
      guidance results in perfect targeting of 5-mm lesions, even by surgical novices.

PMID- 21083798
TI  - Intra-operative ultrasound elasticity imaging for monitoring of hepatic tumour
      thermal ablation.
AB  - BACKGROUND: Thermal ablation is an accepted therapy for selected hepatic
      malignancies. However, the reliability of thermal ablation is limited by the
      inability to accurately monitor and confirm completeness of tumour destruction in
      real time. We investigated the ability of ultrasound elasticity imaging (USEI) to
      monitor thermal ablation. OBJECTIVES: Capitalizing on the known increased
      stiffness that occurs with protein denaturation and dehydration during thermal
      therapy, we sought to investigate the feasibility and accuracy of USEI for
      monitoring of liver tumour ablation. METHODS: A model for hepatic tumours was
      developed and elasticity images of liver ablation were acquired in in vivo animal
      studies, comparing the elasticity images to gross specimens. A clinical pilot
      study was conducted using USEI in nine patients undergoing open radiofrequency
      ablation for hepatic malignancies. The size and shape of thermal lesions on USEI
      were compared to B-mode ultrasound and post-ablation computed tomography (CT).
      RESULTS: In both in vivo animal studies and in the clinical trial, the boundary
      of thermal lesions was significantly more conspicuous on USEI when compared with
      B-mode imaging. Animal studies demonstrated good correlation between the diameter
      of ablated lesions on USEI and the gross specimen (r = 0.81). Moreover, high
      quality strain images were generated in real time during therapy. In patients
      undergoing tumour ablation, a good size correlation was observed between USEI and
      post-operative CT (r = 0.80). CONCLUSION: USEI can be a valuable tool for the
      accurate monitoring and real-time verification of successful thermal ablation of
      liver tumours.

PMID- 21083799
TI  - Ex vivo sentinel lymph node mapping in laparoscopic resection of colon cancer.
AB  - AIM: The study examined the feasibility and potential benefit of ex vivo sentinel
      lymph node (SLN) mapping, including multilevel sectioning (MLS) and
      immunohistochemistry (IHC) in colon cancer patients undergoing laparoscopic
      colectomy. The secondary goals were (i) to identify patient and tumour
      characteristics that might influence the success of the SLN technique, (ii) to
      investigate the extent of lymphadenectomy required to encompass tumour-positive
      nonsentinel lymph nodes (NSLN) and (iii) to ascertain the association of SLN
      status with oncological outcomes. METHOD: SLN mapping was performed after
      specimen extraction using 1% Isosulfan blue. The SLNs were analysed with H&E
      staining after MLS, and if negative, IHC was performed. NSLNs were grouped by
      distance either greater than or less than 4 cm from the tumour. RESULTS: Seventy
      one patients completed the study between 2003 and 2007. Using H&E with MLS, the
      accuracy of SLN mapping was 76%, sensitivity was 52% and the false-negative rate
      was 48%. Excluding patients with clinically positive lymph nodes resulted in a
      significant improvement in accuracy to 81% and decreased the false-negative rate
      to 30%. Furthermore, as the only positive NSLN > 4 cm from the tumour was grossly
      positive, SLN mapping with a 4-cm mesenteric cuff would have given 100%
      sensitivity in patients without macroscopically involved nodes. CONCLUSIONS: SLN
      mapping may be of value in selected patients. It may be possible to accurately
      stage patients with a 4-cm cuff of mesentery, although further validation of this
      proposal is required.

PMID- 21083800
TI  - RNAi trigger fragment truncation attenuates soybean FAD2-1 transcript suppression
      and yields intermediate oil phenotypes.
AB  - Suppression of the microsomal omega6 oleate desaturase during the seed
      development of soybean (Glycine max) with the 420-bp soybean FAD2-1A intron as
      RNAi trigger shifts the conventional fatty acid composition of soybean oil from
      20% oleic and 60% polyunsaturates to one containing greater than 80% oleic acid
      and less than 10% polyunsaturates. To determine whether RNAi could be attenuated
      by reducing the trigger fragment length, transgenic plants were generated to
      express successively shorter 5' or 3' deletion derivatives of the FAD2-1A intron.
      We observed a gradual reduction in transcript suppression with shorter trigger
      fragments. Fatty acid composition was less affected with shorter triggers, and
      triggers less than 60 bp had no phenotypic effect. No trigger sequences
      conferring significantly higher or lower suppression efficiencies were found, and
      the primary determinant of suppression effect was sequence length. The observed
      relationship of transcript suppression with the induced fatty acid phenotype
      indicates that RNAi is a saturation process and not a step change between
      suppressed and nonsuppressed states and intermediate suppression states can be
      achieved.

PMID- 21083801
TI  - Site-specific gene integration in rice genome mediated by the FLP-FRT
      recombination system.
AB  - Plant transformation based on random integration of foreign DNA often generates
      complex integration structures. Precision in the integration process is necessary
      to ensure the formation of full-length, single-copy integration. Site-specific
      recombination systems are versatile tools for precise genomic manipulations such
      as DNA excision, inversion or integration. The yeast FLP-FRT recombination system
      has been widely used for DNA excision in higher plants. Here, we report the use
      of FLP-FRT system for efficient targeting of foreign gene into the engineered
      genomic site in rice. The transgene vector containing a pair of directly oriented
      FRT sites was introduced by particle bombardment into the cells containing the
      target locus. FLP activity generated by the co-bombarded FLP gene efficiently
      separated the transgene construct from the vector-backbone and integrated the
      backbone-free construct into the target site. Strong FLP activity, derived from
      the enhanced FLP protein, FLPe, was important for the successful site-specific
      integration (SSI). The majority of the transgenic events contained a precise
      integration and expressed the transgene. Interestingly, each transgenic event
      lacked the co-bombarded FLPe gene, suggesting reversion of the integration
      structure in the presence of the constitutive FLPe expression. Progeny of the
      precise transgenic lines inherited the stable SSI locus and expressed the
      transgene. This work demonstrates the application of FLP-FRT system for site
      specific gene integration in plants using rice as a model.

PMID- 21083803
TI  - Editorial: Learning how to support older people; menial subservience or expert
      skilfulness?

PMID- 21083802
TI  - Early alpha-fetoprotein response as a predictor for clinical outcome after
      localized concurrent chemoradiotherapy for advanced hepatocellular carcinoma.
AB  - BACKGROUNDS: There are limitations in using only radiological criteria to
      evaluate treatment outcomes in hepatocellular carcinoma (HCC). alpha-fetoprotein
      (AFP) is regarded as an indicator of tumour activity in HCC. AIMS: We present a
      novel correlation between AFP response and survival outcome in patients treated
      with localized concurrent chemoradiotherapy (CCRT). MATERIALS: From 2005 to 2008,
      187 locally advanced HCC patients underwent localized CCRT (external beam
      radiotherapy at 45 Gy over 5 weeks plus a concurrent hepatic arterial infusion of
      5-fluorouracil during the first/fifth week), followed by repetitive hepatic
      arterial infusional chemotherapy (HAIC) with 5-fluorouracil and cisplatin. Among
      them, 149 with an elevated baseline AFP level (>20 ng/ml) were finally studied.
      AFP response was defined as >50% decrease from baseline, 1 month after the
      completion of localized CCRT. RESULTS: Patients' characteristics were as follows:
      median age (52 years); Child-Pugh class A/B (n=137/12 respectively); and portal
      vein thrombosis (n=118). AFP responders (101 patients) had better objective
      responses than AFP non-responders (48 patients) after CCRT (44.5 vs. 12.5%;
      P<0.001) and subsequent HAIC (51.5 vs. 16.7%; P<0.001). Both median progression
      free survival (PFS, 8.1 vs. 3.9 months; P<0.001) and overall survival (OS, 13.3
      vs. 5.9 months; P<0.001) were longer in AFP responders than AFP non-responders.
      In multivariate analysis, AFP response and objective response were independent
      factors affecting PFS and OS. Furthermore, AFP non-responders were more likely to
      have extrahepatic metastasis within 6 months of treatments initiation than AFP
      responders (59.5 vs. 25.9%; P<0.001). CONCLUSIONS: Early AFP response may be
      useful not only in predicting prognosis and treatment response but also in
      establishing optimized treatment plans for HCC.

PMID- 21083804
TI  - Getting prepared for life at home in the discharge process--from the perspective
      of the older persons and their relatives.
AB  - AIM: To examine how older persons in need of home-nursing care and their
      relatives experience the discharge process and develop a model that explains the
      experience. BACKGROUND: The discharge process has well-known deficiencies and is
      therefore a challenging issue requiring improvement in many countries. Research
      focusing on patient-centred factors has attracted very little critical attention.
      DESIGN: Grounded theory was used to analyze semi-structured interviews with 26
      older persons and their relatives. FINDINGS: The analysis resulted in a
      theoretical model that depicts factors determining whether the older persons and
      their relatives feel prepared or unprepared for life at home at the time of
      discharge. CONCLUSIONS: The older persons and/or their relatives felt prepared at
      the time of discharge if their needs were satisfied in the three significant
      areas of preparation. Not only were the professionals' skills of the utmost
      importance in preparing the older persons/relatives, but also the latter's own
      approach if the professionals were unskilled. RELEVANCE FOR CLINICAL PRACTICE: A
      knowledge of the preparation areas and skills can be of use for improving the
      quality of the discharge process from the older persons' and their relatives'
      perspective, i.e. through policies, checklists and teaching programmes.

PMID- 21083805
TI  - Relationships between nurses and older people within the home: exploring the
      boundaries of care.
AB  - AIM: To explore the nature of relationships between nurses and older people
      within the home and to illuminate the nature and quality of caring boundaries
      within this setting. BACKGROUND: Older people are increasingly receiving nursing
      care in the home. There has been little exploration of the nature of the nurse
      older patient relationship within this setting. METHODS: An ethnographic approach
      using semi-structured interviews with 16 community nurses and 13 older patients
      (aged 65 years and over), were undertaken to explore the nature of care
      relationships within the home setting. FINDINGS: The study has highlighted the
      centrality of the location of care and the concept of 'the home' in terms of
      geographical and metaphorical meanings. Moreover, the study has clearly
      illuminated the complex nature of relationships and boundary construction from a
      number of perspectives. CONCLUSION: As the location of care for older people
      continues to move closer to home it is crucial that the implicit qualities that
      are valued within nurse-patient relationships within this context of care, and
      which contribute to the quality of care, are recognized and made more explicit at
      the organizational and policy level. PRACTICE IMPLICATIONS: For nurses working
      within the home there is a clear impetus to clearly define and articulate the
      full breadth of their role, the nature of relationships and issues surrounding
      professional boundary construction within this environment. There is also a need
      for the core qualities that underpin the receipt of care within the home and the
      facets of the nurse-patient relationship valued by older people to be fully
      recognized and accounted for.

PMID- 21083806
TI  - Factors influencing older patients' participation in care: a review of the
      literature.
AB  - BACKGROUND: Over the past 10 years, there has been an increase in the literature
      promoting patient involvement in health care at all levels of the decision-making
      process. AIM: To review the literature on factors influencing patient
      participation in care with a particular focus on the perspective of older people.
      METHOD: Various search engines were used to conduct the review and articles were
      identified through the following databases; CINAHL, CSA ILLUMINA, Science Direct,
      Blackwell Synergy, the Cochrane Library, OVID, SAGE, AHMED, BNI and MEDLINE.
      Research studies ranging from 2000-2007 were selected for inclusion on the basis
      that they investigated patient participation and/or older peoples' involvement in
      health care. FINDINGS: Seven key themes emerged from the literature: the concept
      of participation, the need for older people to be involved, autonomy and
      empowerment, patients' expectations, benefits of participation, factors
      influencing participation and precursors to participation. CONCLUSIONS: Although
      patient participation has received considerable attention in the literature, this
      review highlights the dearth of research from the perspective of older people.
      There is a general consensus that preference for participation should be assessed
      and not assumed, and the review offers a sobering reminder that participation
      should not be achieved at the expense of patient autonomy and choice. RELEVANCE
      TO PRACTICE: Quality care and the most productive use of resources are dependent
      on the public's engagement with health service providers. However, despite being
      central to contemporary nursing practice, this review suggests that the reality
      is not matched by the rhetoric. Future initiatives should focus on supporting
      nurses and other healthcare professionals to develop the competencies required to
      facilitate greater participation by older people who wish to become more involved
      in their care.

PMID- 21083807
TI  - Student nurses' perception and understanding of elder abuse.
AB  - AIM: The aim of this study is to investigate student nurses' perception,
      knowledge and awareness of elder abuse. BACKGROUND: It is evidential that elder
      abuse tends to be unrecognized and is often hidden from public awareness. Nurses
      who work with older people are expected to be knowledgeable of the causes and
      detection of elder abuse. DESIGN: A quantitative approach using a questionnaire
      was used to collect data from 245 student nurses from year 1 and 3 of a 4-year
      bachelor's degree programme. METHOD: Convenience sampling was used to recruit
      participants from the two cohorts of the nursing programme. A 25-item
      questionnaire was used to investigate participants' perception and awareness of
      elder abuse. RESULTS: Some 47.8% (n=86) year 1 students and 76.9% (n=50) year 3
      students perceived that they were not well trained in identifying or handling
      elder abuse. Year 1 and 3 students ranked the top three most common abuses
      differently. In addition, 38% of year 3 students thought that it was largely the
      responsibility of social workers rather than nurses, to deal with cases of elder
      abuse. CONCLUSIONS: The study reveals that nurses-to-be, who are generally
      expected to be part of the joint force to protect older people against abuse, did
      not find themselves adequately prepared to fulfil this responsibility. RELEVANCE
      TO CLINICAL PRACTICE: The findings provide useful information from which more
      comprehensive content about elder abuse can be developed in the gerontological
      nursing curriculum, to better prepare future nurses by increasing their basic
      understanding of elder abuse.

PMID- 21083808
TI  - Editorial: Appreciative inquiry.

PMID- 21083809
TI  - Appreciative inquiry and older people--finding the literature.
AB  - This paper describes the results of a literature search which sought papers
      specifically on appreciative inquiry (AI) and older people. The results of this
      search suggested that there were not many papers which met these criteria, and
      those that did were more often discussion papers rather than research papers.
      This lack of publication belies the observation that research with older people
      could benefit from the positive approach entailed in an AI approach. The reasons
      for this are discussed in the paper, but the possibility is explored that some
      authors may be using AI, but not classifying their studies as this. The studies
      that do explicitly use AI have reported that participants became productively
      engaged in the process, but there is little evidence that this promising start
      has been followed up.

PMID- 21083810
TI  - Appreciating and developing compassionate care in an acute hospital setting
      caring for older people.
AB  - BACKGROUND: There is increasing emphasis in policy, research and practice on the
      importance of caring in health care. Indeed there is much debate about how to
      enhance the caring cultures within which health care is provided. This paper
      argues that a proper systematic analysis of caring practice that works well in
      care environments may help us to move towards a realistic model for the future
      which supports staff, patients and families to give and receive compassionate
      care. AIM: The aim of the project was to explore, develop and articulate
      strategies that enhanced compassionate relationship centred care in an acute
      hospital setting, caring for older people. METHODS: Appreciative action research
      informed the development and evaluation of the project. A range of data
      generation activities were used to examine what worked well. Following detailed
      analysis key processes emerged as being central to delivery of compassionate
      care. Specific action projects were implemented and evaluated to enhance these
      processes necessary for compassionate caring. FINDINGS: Data from the project
      helped to articulate the special and often hidden acts that make up compassionate
      care. In relation to the process of 'knowing who I am and what matters to me'
      data provided evidence of the value of this process and the potential impact to
      care. In addition data about the process of doing appreciative action research
      helped to realise its application and relevance in the health care setting.
      CONCLUSIONS: Findings from this work suggest that there are a number of
      significant processes that help people to deliver compassionate care. These need
      to be articulated, shared more widely across practice, policy and education so
      that we can build on this excellent practice. IMPLICATIONS FOR PRACTICE:
      Appreciative action research adopted in this project is an important methodology
      to supporting practitioners to identify what it is they do well and develop
      practice to try to make the best caring practice happen most of the time.
      Academics, policy makers and practitioners should consider the approach of
      appreciative action research as key to supporting developments in care.

PMID- 21083811
TI  - Promoting compassionate care with the older people: a relational imperative.
AB  - We have been invited to imagine a future where the care for older people goes
      beyond the current paradigm. This article challenges the fundamental assumptions
      that underlie current care practices and, instead, promotes systems and processes
      that elevate nourishing and stimulating relationships with basic dignity, as well
      as personal agency, in the later days of life. Healthcare professionals still
      base current care systems on a medical model that emphasises the diagnosis,
      treatment and cure of disease (Kane RL & West JC, 2005It Shouldn't Be This Way:
      The Failure of Long-Term Care, Vanderbilt University Press, Nashville,
      Tennessee). In contrast, we highlight principles of relating that support care to
      older people during the final stages of life, and promote systems, processes, and
      design elements that constitute compassionate care. To do so, it is necessary to
      move from a model that responds to the dominant regulatory environment to a model
      that is designed in the ongoing processes of human relationships. Specifically,
      we are including all dimensions of relating including relations among the
      residents and between and among residents' families, and all levels and functions
      of caretakers and the community.

PMID- 21083812
TI  - Pork safety: achievements and challenges.
AB  - Safepork is a biennial international symposium for researchers investigating the
      epidemiology and control of foodborne hazards in pork. Current research is
      heavily weighted towards enteric bacterial pathogens for which development of
      reliable practical interventions for farmers has proven frustrating. In contrast,
      modern production practices have greatly reduced the risk of parasitic foodborne
      pathogens. Better understanding of host adaptation of emerging agents is
      important for assessing their potential zoonotic and foodborne risks.

PMID- 21083813
TI  - Description of extended pre-harvest pig Salmonella surveillance-and-control
      programme and its estimated effect on food safety related to pork.
AB  - Salmonella in pork can be combated during pre- or post-harvest. For large
      slaughterhouses, post-harvest measures like decontamination might be cost
      effective while this is less likely with small-to-medium sized slaughterhouses.
      In this study, pre-harvest measures might be more relevant. We describe an
      extended surveillance-and-control programme for Salmonella in finisher pigs,
      which, to establish equivalence to the Swedish control programme, is intended for
      implementation on the Danish island, Bornholm. The effect of the programme on
      food safety was estimated by analysing Salmonella data from pig carcasses
      originating from herds that would have qualified for the programme during 2006
      2008. Food safety was interpreted as prevalence of Salmonella on carcasses as
      well as the estimated number of human cases of salmonellosis related to pork
      produced within the programme. Data from the Danish Salmonella programme were
      obtained from Bornholm. We used a simulation model developed to estimate the
      number of human cases based on the prevalence of Salmonella on carcass swabs.
      Herds are only accepted in the programme if they have one or less seropositive
      sample within the previous 6 months. In this way, the Salmonella load is kept to
      a minimum. The programme is not yet in operation and pigs that qualify for the
      programme are currently mixed at slaughter with those that do not qualify.
      Therefore, we had to assess the impact on the carcass prevalence indirectly. The
      prevalence of Salmonella in carcass swabs among qualifying herds was 0.46% for
      the 3 years as a whole, with 2006 as the year with highest prevalence. According
      to the simulation the expected number of human cases relating to pork produced
      within the programme was below 10. When the programme is in operation, an extra
      effect of separating pigs within the programme from those outside is expected to
      lower the prevalence of Salmonella even further.

PMID- 21083815
TI  - Salmonella in pork cuttings in supermarkets and butchers' shops in Denmark in
      2002 and 2006.
AB  - The prevalence of Salmonella in fresh pork cuttings in Denmark in the years 2002
      and 2006 was investigated at retail and compared with the retail supply pattern.
      A total of 1025 and 3473 samples were taken in 2002 from butcher's shops and
      supermarkets, respectively. The corresponding numbers in 2006 were 259 from
      butchers' shops and 628 from supermarkets. In 2002, 1.2% of all samples were
      positive for Salmonella; butchers' shops and supermarkets had 1.8% and 1.0%
      positive samples, respectively. The overall prevalence in 2006 was 4.2%, with
      prevalence of 8.1% and 2.6% for butchers' shops and supermarkets, respectively.
      Hence, increases around 3- to 5-fold were found. There was neither observed any
      parallel increase in Salmonella positive carcasses in Danish slaughterhouses
      during the study period, nor were any changes in supply routes towards
      slaughterhouses with higher prevalence observed, which could explain the apparent
      increase. We hypothesize that hygiene levels and ability to avoid cross
      contamination and prevent growth of the organism, in the meat processing chain
      after slaughter were the most likely responsible factors. Results from this study
      indicate that the hygiene performance, particularly at retail, has a significant
      impact on the occurrence of Salmonella. This implies that there is no direct link
      between slaughterhouse Salmonella surveillance data and the level of Salmonella
      contamination at retail. To improve risk assessment of Salmonella in fresh pork
      meat, this study underlines the need for comprehensive retail data.

PMID- 21083814
TI  - Slaughterfloor decontamination of pork carcases with hot water or acidified
      sodium chlorite - a comparison in two Australian abattoirs.
AB  - A decontamination trial on the effectiveness of hot water or acidified sodium
      chlorite (SANOVA) treatment on Salmonella spp., Escherichia coli and Total Viable
      Count (TVC) was undertaken on pork carcases prior to primary chilling in two
      large pork abattoirs in Australia using belly-strip excision sampling. A total of
      123 samples from Abattoir A and 400 samples from Abattoir B were cultured and
      analysed. Test pigs were selected from herds with a known high level of on-farm
      Salmonella infection. At Abattoir A, Salmonella spp. were not isolated from
      carcases. The prevalence of E. coli on control carcases was 92.9% compared with
      9.8% for hot water and 12.5% for SANOVA treated carcases. The mean log(10) E.
      coli concentration for control carcases was 0.89 cfu/gram, compared with -0.83
      cfu/gram from hot water and -0.75 cfu/gram from SANOVA treated carcases. The mean
      log(10) TVC for control carcases was 4.06 compared with 1.81 cfu/gram for hot
      water and 2.76 cfu/gram for SANOVA treated carcases. At Abattoir B, the
      prevalence of Salmonella on control carcases was 16% compared with 2.7% for hot
      water and 7.0% for SANOVA treated carcases. The prevalence of E. coli on control
      carcases was 69.3% compared with 22% for hot water and 30% for SANOVA treated
      carcases. The mean log(10) E. coli concentration for control carcases was 0.45
      cfu/gram, compared with -0.65 cfu/gram from hot water and -0.60 cfu/gram from
      SANOVA treated carcases. The mean log(10) TVC for control carcases was 3.00
      cfu/gram compared with 2.10 cfu/gram for hot water and 2.53 cfu/gram for SANOVA
      treated carcases. The reductions in prevalence and mean log(10) concentrations in
      the present trial were all found to be statistically significant and indicate
      that carcases decontamination with either hot water or SANOVA are effective risk
      management options immediately available to the pork industry.

PMID- 21083816
TI  - Risk factors for Salmonella infection in fattening pigs - an evaluation of blood
      and meat juice samples.
AB  - The main objective of this study was to analyse potential herd-level factors
      associated with the detection of Salmonella antibodies in fattening pigs. Two
      independent datasets, consisting of blood and meat juice samples respectively,
      were used. Additional information about husbandry, management and hygiene
      conditions was collected by questionnaire for both datasets. The serological
      analysis showed that 13.8% of the blood samples and 15.7% of the meat juice
      samples had to be classified as Salmonella-positive. Logistic-regression models
      were used to assess statistically significant risk factors associated with a
      positive sample result. The results of the statistical blood sample analysis
      showed that the application of antibiotics increased the odds ratio (OR) by a
      factor of 5.21 (P < 0.001) compared to untreated pigs. A fully slatted floor
      decreased the prevalence of Salmonella as well as the use of protective clothing
      or the cleaning of the feed tube (ORs 0.35-0.54, P < 0.001). It was shown that a
      distance of less than 2 km to other swine herds increased the chance of a
      positive Salmonella result (OR = 3.76, P < 0.001). The statistical analysis of
      the meat juice samples revealed the importance of feed aspects. The chance of
      obtaining a positive meat juice sample increased by a factor of 3.52 (P < 0.001)
      by using granulated feed instead of flour. It also became clear that liquid
      feeding should be preferred to dry feeding (OR = 0.33, P < 0.001). A comparison
      of the blood sample analysis to the meat juice model revealed that the latter was
      less powerful because data structure was less detailed. The expansion of data
      acquisition might solve these problems and improve the suitability of QS
      monitoring data for risk factor analyses.

PMID- 21083817
TI  - Analysis of meat juice ELISA results and questionnaire data to investigate farm
      level risk factors for Salmonella infection in UK pigs.
AB  - The study set out to explore risk factors for Salmonella infection in pigs, based
      on seroprevalence amongst slaughtered pigs, using a large study population of
      holdings and a comprehensive list of farm characteristics. Farm data were
      collected from pig quality assurance schemes and supplemented by a postal
      questionnaire. These data were used with meat juice serology results from ongoing
      abattoir Salmonella surveillance, for a multivariable risk factor analysis,
      modelling the ELISA sample to positive ratio directly (ELISA ratio). The study
      population contained 566 farms, covering a geographically representative spread
      of farms within the United Kingdom, with a mean average of 224 sample results per
      holding over a 4-year period. The model highlighted that temporal factors
      (quarterly and yearly cycles) and monthly meteorological summaries for rainfall,
      sunshine and temperature were associated with Salmonella presence (P < 0.01). The
      ELISA ratio was found to be highest in autumn and lowest in spring and summer,
      whereas yearly averages showed a greater degree of variation than seasonal. Two
      feed variables (homemix and barley) were found to be protective factors, as was a
      conventional, rather than organic or freedom foods, farm enterprise type. The
      number of annual pig deliveries and dead stock collections, and the main cause of
      pig mortality on the farm were found to be associated with Salmonella infection.
      Scottish farms had a lower ELISA ratio than other regions, and an increased
      number of pig farms within a 10-km radius was associated with a higher ELISA
      ratio. The study demonstrated that the analysis of routinely collected data from
      surveillance and quality assurance schemes was cost-effective, with sufficient
      power to detect modest associations between Salmonella and exposure variables.
      The model results can be used to inform on-farm Salmonella control policies and
      could target-specific geographical regions and seasons to assist the efficiency
      of surveillance.

PMID- 21083818
TI  - Use of herd information for predicting Salmonella status in pig herds.
AB  - Salmonella surveillance-and-control programs in pigs are highly resource
      demanding, so alternative cost-effective approaches are desirable. The aim of
      this study was to develop and evaluate a tool for predicting the Salmonella test
      status in pig herds based on herd information collected from 108 industrial
      farrow-to-finish pig herds in Portugal. A questionnaire including known risk
      factors for Salmonella was used. A factor analysis model was developed to
      identify relevant factors that were then tested for association with Salmonella
      status. Three factors were identified and labelled: general biosecurity (factor
      1), herd size (factor 2) and sanitary gap implementation (factor 3). Based on the
      loadings in factor 1 and factor 3, herds were classified according to their
      biosecurity practices. In total, 59% of the herds had a good level of biosecurity
      (interpreted as a loading below zero in factor 1) and 37% of the farms had good
      biosecurity and implemented sanitary gap (loading below zero in factor 1 and
      loading above zero in factor 3). This implied that they, among other things,
      implemented preventive measures for visitors and workers entering the herd,
      controlled biological vectors, had hygiene procedures in place, water quality
      assessment, and sanitary gap in the fattening and growing sections. In total, 50
      herds were tested for Salmonella. Logistic regression analysis showed that factor
      1 was significantly associated with Salmonella test status (P = 0.04). Herds with
      poor biosecurity had a higher probability of testing Salmonella positive compared
      with herds with good biosecurity. This study shows the potential for using herd
      information to classify herds according to their Salmonella status in the absence
      of good testing options. The method might be used as a potentially cost-effective
      tool for future development of risk-based approaches to surveillance, targeting
      interventions to high-risk herds or differentiating sampling strategies in herds
      with different levels of infection.

PMID- 21083819
TI  - Bayesian zero-inflated predictive modelling of herd-level Salmonella prevalence
      for risk-based surveillance.
AB  - The national control programme for Salmonella in Danish swine herds introduced in
      1993 has led to a large decrease in pork-associated human cases of salmonellosis.
      The pork industry is increasingly focused on the cost-effectiveness of
      surveillance while maintaining consumer confidence in the pork food supply. Using
      national control programme data from 2003 and 2004, we developed a zero-inflated
      binomial model to predict which farms were most at risk of Salmonella. We
      preferentially sampled these high-risk farms using two sampling schemes based on
      model predictions resulting from a farm's covariate pattern and its random
      effect. Zero-inflated binomial modelling allows assessment of similarities and
      differences between factors that affect herd infection status (introduction), and
      those that affect the seroprevalence in infected herds (persistence and spread).
      Both large (producing greater than 5000 pigs per annum), and small herds
      (producing less than 2000 pigs per annum) were at significantly higher risk for
      infection and subsequent seroprevalence, when compared with medium sized herds
      (producing between 2000 and 5000 pigs per annum). When compared with herds being
      located elsewhere, being located in the south of Jutland significantly decreased
      the risk of herd infection, but increased the risk of a pig from an infected herd
      being seropositive. The model suggested that many of the herds where Salmonella
      was not detected were infected, but at a low prevalence. Using cost and
      sensitivity, we compared the results of our model based sampling schemes with
      those under the standard sampling scheme, based on herd size, and the recently
      introduced risk-based approach. Model-based results were less sensitive but show
      significant cost savings. Further model refinements, sampling schemes and the
      methods to evaluate their performance are important areas for future work, and
      these should continue to occur in direct consultation with Danish authorities.

PMID- 21083820
TI  - Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS)
      Farm Program: results from finisher pig surveillance.
AB  - In 2006, the Canadian Integrated Program for Antimicrobial Resistance
      Surveillance (CIPARS) Farm Program was implemented in sentinel grower-finisher
      swine herds in Quebec, Ontario, Manitoba, Saskatchewan and Alberta. Herds were
      visited 1-3 times annually. Faecal samples were collected from pens of close-to
      market (CTM) weight (>80 kg) pigs and antimicrobial use (AMU) data were collected
      via questionnaires. Samples were cultured for generic Escherichia coli and
      Salmonella and tested for antimicrobial susceptibility. This paper describes the
      findings of this program between 2006 and 2008. Eighty-nine, 115 and 96 herds
      participated in this program in 2006, 2007 and 2008 respectively. Over the 3
      years, antimicrobial resistance (AMR) levels remained consistent. During this
      period, resistance to one or more antimicrobials was detected in 56-63% of the
      Salmonella spp. isolates and 84-86% of E. coli isolates. Resistance to five or
      more antimicrobials was detected in 13-23% of Salmonella and 12-13% of E. coli.
      Resistance to drugs classified as very important to human health (Category I) by
      the Veterinary Drug Directorate (VDD), Health Canada, was less than or equal to
      1% in both organisms. AMU data were provided by 100 herds in 2007 and 95 herds in
      2008. Nine herds in 2007 and five herds in 2008 reported no AMU. The most common
      route of antimicrobial administration (75-79% of herds) was via feed,
      predominantly macrolides/lincosamides (66-68% of herds). In both 2007 and 2008,
      the primary reasons given for macrolide/lincosamide use were disease prevention,
      growth promotion and treatment of enteric disease. The Category I antimicrobials,
      ceftiofur and virginiamycin were not used in feed or water in any herds in 2008,
      but virginiamycin was used in feed in two herds in 2007. Parenteral ceftiofur was
      used in 29 herds (29%) in 2007 and 20 herds (21%) in 2008. The reasons for
      ceftiofur use included treatment of lameness, respiratory disease and enteric
      disease.

PMID- 21083821
TI  - Evaluation of the risk factors for shedding Salmonella with or without
      antimicrobial resistance in swine using multinomial regression method.
AB  - A multinomial logistic regression method was used to investigate the risk factors
      for antimicrobial resistance (AMR) in Salmonella isolated from faecal samples
      collected on 80 Ontario swine farms in Canada. The samples were classified into
      three groups including Salmonella-negative samples (S-), Salmonella-positive
      samples without AMR (S+AMR-) and Salmonella-positive samples with AMR (S+AMR+).
      The samples collected directly from pigs had a greater chance to be positive for
      Salmonella with AMR compared to those samples collected from the pen floor. The
      odds of culturing Salmonella with or without AMR was higher if pelleted feed was
      used compared with mash or liquid feed (P < 0.001). The faecal samples collected
      on farrow-to-finish farms had a significant lower chance of testing positive for
      Salmonella with multidrug resistance than the samples from grow-finisher farms (P
      = 0.004). The chance of culturing Salmonella without AMR on farms with a
      continuous system was higher than on farms with an all-in/all-out system (P =
      0.009). However, there was no significant association between the flow system and
      recovery of Salmonella with AMR. The larger farms were more likely to be in
      S+AMR+ group than in S- group (P < 0.001) whereas herd size did not appear as a
      risk factor for being in S+AMR- group compared with S- group. These findings
      indicate that although on-farm antimicrobial use is one component of resistance,
      there might be other farm management factors that also affect the development of
      emerging resistant bacterial foodborne pathogens on swine farms. Finding
      different risk factors for shedding Salmonella with or without antimicrobial
      resistance would help to take the appropriate approach to each group if a control
      programme were to be implemented or an intervention applied.

PMID- 21083822
TI  - Use of a bacterial antimicrobial resistance gene microarray for the
      identification of resistant Staphylococcus aureus.
AB  - As diagnostic and surveillance activities are vital to determine measures needed
      to control antimicrobial resistance (AMR), new and rapid laboratory methods are
      necessary to facilitate this important effort. DNA microarray technology allows
      the detection of a large number of genes in a single reaction. This technology is
      simple, specific and high-throughput. We have developed a bacterial antimicrobial
      resistance gene DNA microarray that will allow rapid antimicrobial resistance
      gene screening for all Gram-positive and Gram-negative bacteria. A prototype
      microarray was designed using a 70-mer based oligonucleotide set targeting AMR
      genes of Gram-negative and Gram-positive bacteria. In the present version, the
      microarray consists of 182 oligonucleotides corresponding to 166 different
      acquired AMR gene targets, covering most of the resistance genes found in both
      Gram-negative and -positive bacteria. A test study was performed on a collection
      of Staphylococcus aureus isolates from milk samples from dairy farms in Quebec,
      Canada. The reproducibility of the hybridizations was determined, and the
      microarray results were compared with those obtained by phenotypic resistance
      tests (either MIC or Kirby-Bauer). The microarray genotyping demonstrated a
      correlation between penicillin, tetracycline and erythromycin resistance
      phenotypes with the corresponding acquired resistance genes. The hybridizations
      showed that the 38 antimicrobial resistant S. aureus isolates possessed at least
      one AMR gene.

PMID- 21083823
TI  - Phenotypic and genotypic heterogeneity of Campylobacter coli within individual
      pigs at farm and slaughter in the US.
AB  - The aim of this study was to determine the phenotypic and genotypic diversity of
      multiple Campylobacter isolates (n = 3 per sample) present within individual
      (heterogeneity) pig faecal and carcass samples at farm and slaughter,
      respectively. We isolated 1459 Campylobacter coli (1110 on farm and 349 from
      slaughter) from 908 pigs and 757 carcasses and characterized them for their
      antimicrobial susceptibility profile to a panel of six antimicrobials using the
      agar dilution method. Overall, we detected a significantly higher Campylobacter
      prevalence at the farm (54.7%) than at slaughter (19%) level (P < 0.05). C. coli
      isolates were resistant most commonly to tetracycline (66.2%) and erythromycin
      (53.6%) while fluoroquinolone resistance was detected in isolates (n = 17) only
      from the farm level. Phenotypic diversity of C. coli isolates at the 4-fold
      minimum inhibitory concentration levels within the same sample was detected in
      38.6% (n = 192) pigs and 40.2% (n = 58) carcass swabs with no significant
      difference between the two sources (P = 0.72). Phenotypic heterogeneity based on
      the antimicrobial resistance patterns was observed in 32.5% (n = 162) of the farm
      samples and in 30.5% (n = 44) carcass swabs at slaughter (P = 0.64). A subset of
      40 isolates representing ten pigs and eight carcass samples (originating from
      separate pigs) were further genotyped by multi locus sequence typing. The
      observation of phenotypic diversity was replicated at the genotypic level, as it
      was highlighted by the 22 sequence types which represented the 40 isolates. In
      conclusion, we detected multiple C. coli subtypes from individual pig or carcass
      samples indicating unprecedented level of heterogeneity. Our study clearly
      signifies the importance of testing multiple colonies to make appropriate and
      valid conclusions in epidemiological-based studies.

PMID- 21083824
TI  - Evaluation of three commercial enzyme-linked immunosorbent assays for the
      detection of antibodies against Salmonella spp. in meat juice from finishing pigs
      in Spain.
AB  - The control of animal salmonellosis is considered as a major objective in Europe
      and indirect ELISAs will be important tools for the implementation of control
      programs for this infection in pigs. We analyse the results yielded by three
      commercial ELISAs (Herdcheck Swine Salmonella, SALMOTYPE Pig Screen, and
      PrioCHECK Salmonella) on meat juice samples from a population of slaughter pigs
      of Aragon, NW Spain, to assess their efficacy using traditional and latent-class
      approaches. Overall, the Herdcheck Swine Salmonella detected more Salmonella
      infected pigs than the other two tests, but its relative sensitivity was low
      (65.9%). A similar result was observed when only serotypes detectable by this
      test were considered (69.1%). When a Bayesian approach was used the Herdcheck
      Swine Salmonella showed also the highest overall accuracy (sensitivity = 88% and
      specificity = 74%). Our results suggest that a relatively small proportion of the
      observed prevalence in herds would be explained by using these ELISAs. Also, this
      study points out that when different ELISA tests are used within the same herd,
      results may differ substantially. Thus, caution is advised if it is decided to
      use these assays for herd health classification in Spanish Salmonella control
      programs.

PMID- 21083825
TI  - Comparison of bacterial culture and real-time PCR for the detection of Salmonella
      in grow-finish pigs in Western Canada using a Bayesian approach.
AB  - The study objective was to evaluate the accuracy of a real-time polymerase chain
      reaction (RT-PCR) and a culture protocol used to detect Salmonella in the faeces
      of grow-finish pigs using a Bayesian approach. The RT-PCR was invA-gene-based
      assay, while the culture protocol included pre-enrichment in buffered peptone
      water, selective enrichment in tetrathionate and Rappaport-Vassiliadis broths,
      and isolation on semi-solid (modified semi-solid RV) or solid (XLT4, Rambach)
      agar plates. Bayesian analysis was performed using a two-test, two-population
      model with dependence between culture and RT-PCR and compared to a second model
      with conditional independence between these two tests. Two hundred and ninety
      three individual faecal and 294 pooled pen samples from grow-finish pig collected
      from 10 farms were tested and results were divided into two groups according to
      herd size (five herds <250 sows, five herds with >400 sows). In the dependence
      model, RT-PCR sensitivity (Se) and specificity (Sp) were estimated to be 90% (95%
      probability interval 74, 97) and 99% (98, 99), respectively. Culture Se was 92%
      (75, 99), while culture Sp was considered 100% as all culture-positive samples
      were confirmed by serotyping. In the conditional independence model, RT-PCR Se
      and Sp, and culture Se, were 96% (93, 98), 99% (98, 100) and 97% (94, 100),
      respectively. The dependence model resulted in posterior estimates of Se that
      were lower and with broader probability intervals than the independence model,
      indicating that when RT-PCR and culture are evaluated relative to each other, the
      correlation between these tests is an important source of bias and should be
      adjusted for during analysis. The RT-PCR evaluated in this study performed almost
      comparably to culture; given the cost savings associated with using this test and
      more timely results, the RT-PCR may be a useful alternative to culture for
      screening large numbers of samples, particularly when Salmonella prevalence is
      low.

PMID- 21083826
TI  - Examining heterogeneity in the diagnostic accuracy of culture and PCR for
      Salmonella spp. in swine: a systematic review/meta-regression approach.
AB  - The accuracy of bacterial culture and PCR for Salmonella in swine was examined
      through systematic review of existing primary research in this field. A
      replicable search was conducted in 10 electronic databases. All steps of the
      review were conducted by two reviewers: to identify relevant publications, to
      assess their methodological soundness and reporting, and to extract raw data or
      reported test accuracy estimates. Meta-analyses and meta-regression were
      performed: to evaluate pooled estimates of test sensitivity (Se) and specificity
      (Sp), to identify variables explaining the variation in reported test estimates,
      and to evaluate the association between these variables and reported test Se and
      Sp. Twenty-nine studies were included in the review. Unique test evaluations
      reported in these 29 studies were categorized according to the type of test
      comparison: culture versus culture (n = 134 test evaluations) and PCR versus
      culture (n = 21). We identified significant heterogeneity among evaluations for
      each test category. For culture, more heterogeneity was caused by differences in
      individual test protocols (52%) than overall differences between studies (16%).
      Enrichment temperature, study population, agar and enrichment type were
      significantly associated with variation in culture Se. Furthermore, interaction
      between enrichment temperature and enrichment type was detected. For PCR, most of
      the heterogeneity was caused by overall differences between studies (65-70%);
      sample type and study size were associated with variation in reported PCR Se and
      Sp. The overall methodological soundness and/or reporting of primary studies
      included in this review were poor, with variable use of reference standards, and
      consistent lack of the use or reporting of blinding, randomization and subject
      (sample) selection criteria. Consequently, the food safety and veterinary public
      health research community should formally consider ways for standardizing the
      conduct and reporting of this type of research.

PMID- 21083827
TI  - Human C. difficile infections are increasing in incidence and severity.

PMID- 21083828
TI  - Environmental sampling for Salmonella spp. in Colorado animal shelters.
AB  - Salmonella enterica is an important zoonotic agent and nosocomial infections and
      epidemics have occurred in animal facilities. The objective of this study was to
      estimate the prevalence of Salmonella in the environment in animal shelters. From
      12 to 25 samples were taken from each shelter to represent environmental
      contamination. Samples were collected from surfaces in areas used by animals and
      in public access areas including animal receiving rooms, kennels, paediatric
      wards, treatment, visitation rooms, isolation, euthanasia, outdoor runs and play
      areas, reception rooms, animal transport vehicles, offices, break rooms and
      restrooms. Samples were tested for Salmonella and compared within shelters to
      identify high- and low-risk areas; and between shelters to identify differences
      in environmental contamination by geographical location, infection control
      policies, and shelter size characteristics. Twenty-eight per cent of sampled
      Colorado shelters had environmental Salmonella contamination. Two regions in the
      eastern 1/3 of the state had prevalences of 30% and 100%. Within-shelter sample
      prevalence ranged from 0 to 100%. Results of this study indicate that animal
      shelters can be frequently contaminated with Salmonella spp., a variety of
      Salmonella species may be present, contamination can be widespread within a
      facility and recovered isolates may harbour antibiotic resistance The findings
      from this study may influence and help focus educational policy on issues of
      infection control and zoonotic disease awareness in animal shelters.

PMID- 21083829
TI  - Computational evaluation of platelet activation induced by a bioprosthetic heart
      valve.
AB  - It is known that bioprosthetic heart valves (BHVs) have better hemodynamics and
      lower thromboembolic events compared with their mechanical counterparts; however,
      patients implanted with BHVs still face the potential of such complications. The
      risk of a clinical thromboembolism is on average 0.7% per year in patients with
      tissue valves in sinus rhythm. In this study, we developed a computational fluid
      dynamic (CFD) model of a BHV implanted in an aortic root and investigated the BHV
      induced platelet activation using a damage accumulation model previously applied
      to mechanical valves. The CFD model was validated against published experimental
      data, including the flow velocity profile across the valve and the transvalvular
      pressure drop, and close matches were obtained. Hemodynamic performance measures
      such as flow velocity, turbulent kinetic energy, and wall shear stress were
      explored. Lagrangian particle tracking was used to calculate the extent of
      platelet activation for central bulk flow and flow in the vicinity of the
      leaflets. A peak flow of 2.22 m/s was observed at 40 msec after peak systole in
      the vicinity of a fold at the base of the leaflets. With the platelet activation
      expressed as 0-100% of activation threshold levels, mean damage on one pass was
      2.489 * 10(-7)% and maximum damage on one pass was 8.778 * 10(-4)%. Our results
      suggested that the potential for BHV-induced platelet activation was low and that
      the leaflet's fully open geometry might play a role in the extent of blood
      element damage.

PMID- 21083830
TI  - Bone marrow combined with dental bud cells promotes tooth regeneration in
      miniature pig model.
AB  - Growth factors and morphogens secreted by bone marrow mesenchymal stem cells
      (BMSCs) of bone marrow fluid may promote tooth regeneration. Accordingly, a
      tissue engineering approach was utilized to develop an economical strategy for
      obtaining the growth factors and morphogens from BMSCs. Unerupted second molar
      tooth buds harvested from miniature pigs were cultured in vitro to obtain dental
      bud cells (DBCs). Bone marrow fluid, which contains BMSCs, was collected from the
      porcine mandible before operation. DBCs suspended in bone marrow fluid were
      seeded into a gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer scaffold
      (GCHT scaffold). The DBCs/bone marrow fluid/GCHT scaffold was autografted into
      the original alveolar sockets of the pigs. Radiographic and histological
      examinations were applied to identify the structure of regenerated tooth at 40
      weeks postimplantation. The present results showed that one pig developed a
      complete tooth with crown, root, pulp, enamel, dentin, odontoblast, cementum,
      blood vessel, and periodontal ligament in indiscriminate shape. Three animals had
      an unerupted tooth that expressed dentin matrix protein-1, vascular endothelial
      growth factor, and osteopontin; and two other pigs also had dental-like structure
      with dentin tubules. This study reveals that DBCs adding bone marrow fluid and a
      suitable scaffold can promote the tooth regeneration in autogenic cell
      transplantation.

PMID- 21083831
TI  - The course of substance use disorders in patients with borderline personality
      disorder and Axis II comparison subjects: a 10-year follow-up study.
AB  - AIM: The purpose of this study is to detail the course of substance use disorders
      (SUDs) over 10 years of prospective follow-up among patients with borderline
      personality disorder (BPD) and Axis II comparison subjects. DESIGN: This study
      uses data from the McLean Study of Adult Development (MSAD), a multi-faceted
      study of the longitudinal course of BPD using reliable repeated measures
      administered every 2 years over a decade of prospective follow-up. SETTING: All
      subjects were initially in-patients at McLean Hospital in Belmont Massachusetts.
      PARTICIPANTS; A total of 290 patients with BPD and 72 Axis II comparison subjects
      were assessed at baseline and five waves of follow-up. MEASUREMENTS: The
      Structured Clinical Interview for DSM-III-R Axis I Disorders (SCID-I), the
      Revised Diagnostic Interview for Borderlines (DIB-R) and the Diagnostic Interview
      for DSM-III-R Personality Disorders (DIPD-R) were administered six times.
      Generalized estimating equations were used to assess longitudinal prevalence of
      SUDs. Kaplan-Meier analyses were used to assess time-to-remission, recurrence and
      new onsets of SUDs. RESULTS: The prevalence of SUDs among borderline patients and
      Axis II comparison subjects declined significantly over time, while remaining
      significantly more common among those with BPD. More than 90% of borderline
      patients meeting criteria for a SUD at baseline experienced a remission by 10
      year follow-up. Recurrences and new onsets of SUDs were less common (35-40% and
      21-23%). CONCLUSIONS: Remissions of alcohol and drug abuse/dependence among
      borderline patients are both common and relatively stable. Results also suggest
      that new onsets of these disorders are less common than might be expected.

PMID- 21083832
TI  - Can stand-alone computer-based interventions reduce alcohol consumption? A
      systematic review.
AB  - AIM: To determine the effects of computer-based interventions aimed at reducing
      alcohol consumption in adult populations. METHODS: The review was undertaken
      following standard Cochrane and Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidance for systematic reviews. The literature was
      searched until December 2008, with no restrictions on language. Randomized trials
      with parallel comparator groups were identified in the form of published and
      unpublished data. Two authors independently screened abstracts and papers for
      inclusion. Data extraction and bias assessment was undertaken by one author and
      checked by a second author. Studies that measured total alcohol consumption and
      frequency of binge drinking episodes were eligible for inclusion in meta
      analyses. A random-effects model was used to pool mean differences. RESULTS:
      Twenty-four studies were included in the review (19 combined in meta-analyses).
      The meta-analyses suggested that computer-based interventions were more effective
      than minimally active comparator groups (e.g. assessment-only) at reducing
      alcohol consumed per week in student and non-student populations. However, most
      studies used the mean to summarize skewed data, which could be misleading in
      small samples. A sensitivity analysis of those studies that used suitable
      measures of central tendency found that there was no difference between
      intervention and minimally active comparator groups in alcohol consumed per week
      by students. Few studies investigated non-student populations or compared
      interventions with active comparator groups. CONCLUSION: Computer-based
      interventions may reduce alcohol consumption compared with assessment-only; the
      conclusion remains tentative because of methodological weaknesses in the studies.
      Future research should consider that the distribution of alcohol consumption data
      is likely to be skewed and that appropriate measures of central tendency are
      reported.

PMID- 21083833
TI  - Use of nicotine replacement therapy for smoking reduction and during enforced
      temporary abstinence: a national survey of English smokers.
AB  - AIMS: To assess the prevalence of nicotine replacement therapy (NRT) use for
      smoking reduction (SR) and temporary abstinence (TA), the association between the
      two and the strength of the association between NRT use for SR or TA and socio
      demographic characteristics, cigarette consumption and past quit attempts.
      DESIGN: Cross-sectional monthly surveys. SETTING: England. PARTICIPANTS: A total
      of 11, 414 smokers. MEASUREMENTS: Participants were asked (i) whether they were
      reducing the amount they smoked: if so, whether they used NRT; and (ii) whether
      they used NRT for TA. Demographic characteristics, daily cigarette consumption
      and whether a quit attempt had been made in the past 12 months were also
      assessed. FINDINGS: Of the participants, 56% were attempting SR, 14% were using
      NRT for SR and 14% were using NRT for TA. Use of NRT for SR and TA were highly
      correlated. The nicotine patch was the most commonly used form of NRT. The use of
      NRT for SR, compared with unassisted SR, was more common among older smokers,
      while the use of NRT for TA was more common among women. Cigarette consumption
      was higher in those using NRT for SR than those attempting SR without NRT. The
      use of NRT for SR and TA was associated positively with past quit attempts.
      CONCLUSIONS: Nicotine replacement therapy use for smoking reduction and temporary
      abstinence is common in England. The use of NRT for SR and TA does not appear to
      be associated with lower cigarette consumption relative to SR or TA without NRT,
      but is associated with a higher rate of past quit attempts.

PMID- 21083834
TI  - Maternal risk factors for small-for-gestational age newborns in Japanese
      dichorionic twins.
AB  - AIM: To investigate the maternal risk factors for small-for-gestational age (SGA)
      newborns in Japanese dichorionic (DC) twins. METHODS: A retrospective study was
      conducted from 2003 to 2008 on 340 DC twin pregnancies resulting in two live
      births. Newborns were classified as SGA if their birth weight was below the 10th
      percentile according to Japanese singleton norms. Statistical differences were
      evaluated between pregnancies resulting in appropriate-for-gestational age (AGA)
      pairs and those resulting in at least one SGA neonate. RESULTS: The study
      population consisted of AGA/AGA (50.8%), AGA/SGA (37.0%) and SGA/SGA pairs
      (12.0%). Logistic regression analysis identified significant interrelations for
      SGA with maternal nulliparity (odds ratio [OR] 0.52, 95% confidence interval [CI]
      0.30-0.91), smoking (OR 3.25, 95% CI 1.09-9.66), assisted reproductive technology
      (OR 0.52, 95% CI 0.30-0.89), pregnancy-induced hypertension (OR 2.00, 95% CI 1.01
      4.31), pregravid weight (kg) (unitary OR 0.94, 95% CI 0.91-0.97) and monthly
      weight gain (kg/month) (unitary OR 0.25, 95% CI 0.14-0.44). Bivariable receiver
      operating characteristic curves were generated for monthly weight gain (area
      under the curve [AUC] 0.626, cutoff 1.41 kg/month, P<0.001) and total weight gain
      (AUC 0.615, cutoff 14.0 kg, P<0.001). CONCLUSION: Cigarette smoking and weight
      gain control are relatively modifiable factors for which interventional
      management is necessary to avoid perinatal problems arising from SGA pregnancy.
      Further studies are needed to investigate optimal nutrition, health guidance and
      subsequent weight gain control that lead to concrete improvement in maternal and
      infant prognoses.

PMID- 21083835
TI  - Laparoscopically assisted vaginal hysterectomy: a novel method.
AB  - This paper describes a novel method of facilitating laparoscopically assisted
      vaginal hysterectomy (LAVH) uniquely distinguished by commencing vaginally and
      finishing laparoscopically. For this technique a specially designed uterine
      manipulator has been developed.

PMID- 21083836
TI  - Uterine rupture secondary to placenta percreta in a near-term pregnant woman with
      a history of hysterotomy.
AB  - Uterine rupture during near-term pregnancy is a life-threatening condition. A 31
      year-old pregnant woman with a breech presentation at the gestation age of 35(+2)
      weeks had complained of a dull abdominal pain for days. She was treated 2 years
      ago with bilateral uterine artery ligation and hysterotomy for removal of the
      retained placenta. An aggravation of abdominal pain occurred suddenly 4 h after
      hospitalization. The cardiotocogram showed a fetal heart beat with loss of
      variability, but increasing deceleration. An urgent cesarean section was
      performed because of suspected placenta abruption. After successful delivery of
      the fetus, a protruding placental tissue was found on the fundal uterine wall. We
      performed wedge resection of the ruptured uterine wall with the aid of an
      intrauterine muscle injection of 20 IU oxytocin, a local injection of diluted
      vasopressin (1:60) into the myometrium around and into the rupture site, an
      intramuscular injection of 0.2 mg methylergonovine, and primary repair of the
      defect, but in vain. Cesarean hysterectomy was used to control the intractable
      bleeding. The accumulated blood loss was more than 10,000 mL. The final pathology
      confirmed placenta percreta with uterine rupture. Luckily, both mother and fetus
      recovered well and were discharged 7 days later. We concluded that women with
      retained placenta and/or postpartum hemorrhage managed by previous hysterotomy
      and uterine artery ligation still need careful prenatal care, since the
      possibility of re-occurrence of the placenta percreta is easily overlooked and
      may result in a further life-threatening situation, such as the uterine rupture
      in this case.

PMID- 21083837
TI  - Case of uterine leiomyoma showing fludeoxyglucose uptake on F-18 fludeoxyglucose
      positron emission tomography/computed tomography.
AB  - In order not to over treat uterine leiomyoma and to avoid overlooking uterine
      leiomyosarcoma, a highly reliable diagnostic method has been thought.
      Occasionally, it is difficult to discriminate uterine leiomyoma from uterine
      leiomyosarcoma. Recently positron emission tomography/computed tomography
      (PET/CT) has been proved useful in assessing pelvic malignancies. We experienced
      a case of uterine leiomyoma showing increased F-18 fludeoxyglucose uptake on
      PET/CT in a postmenopausal woman. However, histological analysis demonstrated
      benign leiomyoma by the hysterectomy. Immunohistochemical analysis of glucose
      transporter-1 showed negative in leiomyoma. Our case indicates that uterine
      leiomyoma in a postmenopausal woman may show false positive result of PET/CT.

PMID- 21083838
TI  - The effect of marital status on pregnancy outcome in Israel: a retrospective case
      control study.
AB  - AIMS: Previous studies have observed an association between unmarried status of
      the mother and adverse perinatal outcome such as increased rate of preterm
      deliveries, low birthweight and small-for-gestational-age infants. In Israel,
      attendance of prenatal care is imposed by the state and is not related to
      socioeconomic status; therefore, unmarried women are expected to have a similar
      prenatal care as married women. The objective of this study is to test the
      hypothesis that unmarried and married pregnant women have a similar perinatal
      outcome. MATERIAL & METHODS: In a retrospective case-control study, analysis of
      the records of women who gave birth at the delivery ward of Edith Wolfson Medical
      Center (a tertiary health care center) over a one-year period (2005) with respect
      to marital status was performed. The cases group included 304 unmarried women who
      were matched with 1:1 ratio for maternal age, parity, and number of fetuses in
      the current pregnancy. RESULTS: Unmarried women (n = 304) were more likely to
      smoke during pregnancy (35.2% vs 15.2%, P < 0.001), had a longer second stage
      (44.4 +/- 9.8 min vs 54.4 +/- 4.4 min, P < 0.05) and a shorter first stage (484.0
      +/- 34.8 min vs 421.0 +/- 25.3 min P < 0.05) of labor. The unmarried women had
      similar length of gestation, preterm delivery rate, mode of delivery, low
      birthweight rates, low Apgar scores or meconium passage during labor as married
      women. CONCLUSION: In Israel, unmarried and married pregnant women may have
      almost similar pregnancy outcomes on length of gestation, mode of delivery and
      Apgar score.

PMID- 21083839
TI  - Role of uterine artery Doppler velocimetry indices and plasma adrenomedullin
      level in women with unexplained recurrent pregnancy loss.
AB  - AIM: To evaluate uterine artery Doppler flow resistance and plasma adrenomedullin
      levels in women with unexplained recurrent pregnancy loss (RPL) compared to
      controls. MATERIAL & METHODS: Eighty-three women, who attend the department of
      Obstetrics and Gynecology, Benha University, Egypt, participated in this study
      (RPL group: n=40, and control group: n=43). Uterine artery Doppler and plasma
      adrenomedullin (AM) (pg/mL) levels were measured for all women in the mid-luteal
      phase of a non-pregnant cycle. RESULTS: Both uterine artery pulsatility index
      (PI) and AM levels were significantly higher in RPL group compared to controls
      (2.71 +/- 0.259 vs 2.06 +/- 0.194 for PI and 287.5 +/- 80.4 pg/mL vs 156.1 +/-
      39.8 pg/mL for AM, P<0.01). Uterine artery PI had a significant positive
      correlation with plasma AM levels both in the RPL group (r=0.645, P<0.001) and in
      the control group (r=0.384, P=0.011). Number of previous miscarriages in RPL
      group was significantly correlated with both uterine artery PI (r=0.838, P=0.015)
      and plasma AM levels (r=0.509, P=0.001). CONCLUSIONS: Uterine artery PI may be
      useful in identifying women with unexplained RPL who have impaired uterine
      circulation. Plasma AM may serve as a biochemical marker for RPL caused by
      impaired uterine perfusion.

PMID- 21083840
TI  - Maternal death analysis from the Japanese autopsy registry for recent 16 years:
      significance of amniotic fluid embolism.
AB  - AIM: To clarify the cause of maternal deaths, an autopsy is essential. However,
      there has been no systemic analysis of maternal death in Japan based on autopsy
      cases. MATERIAL & METHODS: Maternal death reports were retrieved from a large
      amount of registered autopsy data on maternal death in the series of 'Annual of
      pathological autopsy cases in Japan'. These files contain 468,015 autopsy records
      from 1989 to 2004. We collected 193 cases of maternal death due to direct
      obstetric causes. We recorded all the data into Excel files. Then we analyzed the
      causes of death and classified them into 11 categories. RESULTS: The causes of
      maternal death were as follows: amniotic fluid embolism (AFE), 24.3%;
      disseminated intravascular coagulation (DIC) related to pregnancy-induced
      hypertension, 21.2%; pulmonary thromboembolism, 13.0%; injury to the birth canal,
      11.4%; medical and surgical complications, 9.8%; and atonic bleeding or DIC of
      unknown cause, 8.3%. A discrepancy between the clinical diagnosis and
      pathological diagnosis was frequently observed in cases of AFE, septic DIC and
      injury to the birth canal. AFE diagnosed by autopsy was often clinically
      diagnosed as atonic bleeding or DIC of unknown cause before death. Half of the
      cases of AFE diagnosed by autopsy were associated with DIC. CONCLUSION: We found
      that AFE, DIC related to pregnancy-induced hypertension, pulmonary
      thromboembolism and injury to the birth canal were the major causes of maternal
      death in Japan. AFE had various clinical features such as uterine atony and DIC
      in addition to pulmonary cardiac collapse.

PMID- 21083841
TI  - Endometrioid ovarian cancer and endometriotic cells exhibit the same alteration
      in the expression of interleukin-1 receptor II: to a link between endometriosis
      and endometrioid ovarian cancer.
AB  - AIM: Endometrioid carcinoma of the ovary is the third most common type of
      epithelial ovarian cancer. Endometrioid tumors as well as endometriotic implants
      are characterized by the presence of epithelial cells, stromal cells, or a
      combination of booth, that resemble the endometrial cells, suggesting a possible
      endometrial origin of these tumors. Th1 cytokines including interleukin (IL)-1
      have been reported to be involved in both endometriosis and ovarian
      carcinogenesis. We assessed the expression of receptors of IL-1 (IL-1RI and IL
      1RII, the signal transducer and the specific inhibitor of IL-1, respectively) in
      cells of the most common subtypes of ovarian cancer compared to endometrial
      cells. MATERIAL & METHODS: IL1-Rs expression was analyzed at the levels of the
      protein and mRNA using immunofluorescent and real-time polymerase chain reaction
      methods, respectively. RESULTS: We showed that endometrioid cells exhibit a
      specific decrease of IL-1RII expression, whereas IL-1RI was constantly expressed
      in all studied cell subtypes. CONCLUSION: As already reported in endometriotic
      cells, endometrioid ovarian cancer cells exhibit the same alteration in the
      expression of IL-1RII, a key protector against tumorigenic effects of IL-1. Our
      findings highlight a common signature between endometrioid ovarian cancer and
      implants of endometriosis, which needs to be fully explored.

PMID- 21083842
TI  - Squamous cell carcinoma arising from mature cystic teratoma of the ovary with
      synchronous endometrial adenocarcinoma.
AB  - Squamous cell carcinoma arising from a mature cystic teratoma of the ovary is a
      rare event representing only 1-2% of all mature cystic teratomas. Furthermore,
      the synchronous occurrence of a second malignancy in this setting is extremely
      rare. A 63-year-old woman presented with a pelvic mass which was diagnosed as a
      left ovarian mature cystic teratoma preoperatively by ultrasonography. The frozen
      section of the mass revealed a left ovarian mature cystic teratoma with a focus
      of squamous cell carcinoma. Subsequently surgical staging procedure for ovarian
      cancer was performed. The final pathologic diagnosis was squamous cell carcinoma
      in mature cystic teratoma of the ovary, and synchronous endometrial
      adenocarcinoma with a mixture of endometrioid and mucinous subtypes as an
      incidental finding. The combination of these two synchronous cancers is unique
      and to the best of our knowledge, this has not been previously reported in the
      English language literature.

PMID- 21083843
TI  - Decreasing retinol and alpha-tocopherol concentrations in human milk and infant
      formula using varied bottle systems.
AB  - Expressing human milk has become a more common alternative for mothers, as the
      average work demand has increased. As more mothers must work, bottle feeding
      trends are increasingly common. The handling and storage of human milk introduce
      the risk of degradation to expressed human milk and infant formula. In following
      a 20-minute simulated feeding, Vitamin C has been found to degrade. Vitamin C
      acts as an anti-oxidant and is responsible for shielding other nutrients from
      oxidation, such as retinol and alpha-tocopherol. By analyzing a 20-minute
      simulated feeding, retinol and alpha-tocopherol each displayed decreases over
      time significantly different than that of the Control, which was milk not exposed
      to bottle feeding. In human milk, retinol showed as high as a 9.5% decrease
      compared to the Control. Similar trends were seen with the infant formula
      samples. The correlation between degradation and bottle feeding systems was
      dependent upon the formation of bubbles in the milk as the milk was removed from
      the bottle. The analysis indicated a decrease of up to 12%, as seen in retinol,
      and 35%, as seen in alpha-tocopherol. These decreases in retinol and alpha
      tocopherol should be considered when using a bottle feeding system to deliver
      either human milk or formula to an infant. More research is necessary to
      determine the effect of this decrease on the nutritional status of infants,
      particularly premature infants, who are at higher risk for nutrient deficiencies.

PMID- 21083845
TI  - Dermatoscopy of flat pigmented facial lesions: diagnostic challenge between
      pigmented actinic keratosis and lentigo maligna.
AB  - BACKGROUND: The similarity between clinical pictures of pigmented actinic
      keratosis (PAK) and lentigo maligna (LM) is well known. OBJECTIVES: To
      investigate the frequency of dermatoscopic findings suggestive of LM/lentigo
      maligna melanoma (LMM) in the other facial pigmented skin lesions (FPSL) and to
      assess the distinguishing dermoscopic criteria of PAK and LM. METHODS: Eighty
      nine FPSL were evaluated with conventional dermatoscopy. The lesions showing one
      or more dermatoscopic features considered as specific patterns for the diagnosis
      of LM/LMM, mainly slate-grey to black dots and globules, slate-grey areas,
      annular-granular pattern, asymmetrical pigmented follicular openings, black
      blotches, rhomboidal structures, hyperpigmented rim of follicular openings, slate
      grey streaks and dark streaks, were included in the study selectively. RESULTS:
      PAK was diagnosed in 67, LM or LMM in 20 and lichen planus-like keratosis in two
      lesions, histopathologically. Eleven essential dermatoscopic features were
      observed in facial PAK: slate-grey dots (70%); annular-granular pattern (39%);
      rhomboidal structures (36%); pseudonetwork (36%); black globules (34%); slate
      grey globules (33%); black dots (30%); asymmetrical pigmented follicular openings
      (25%); hyperpigmented rim of follicular openings (21%); slate-grey areas (18%);
      and streaks (3%). CONCLUSIONS: PAK has a striking similarity to LM/LMM in
      clinical and dermatoscopic features, thus representing a diagnostic challange.
      All dermatoscopic findings except black blotches were observed in PAK. As
      dermatoscopic diagnosis of a pigmented skin lesion cannot be based on the
      presence of a single criterion, we may conclude that histopathology still remains
      the gold standard for correct diagnosis.

PMID- 21083847
TI  - Age- and region-specific effects of anticonvulsants and bumetanide on 4
      aminopyridine-induced seizure-like events in immature rat hippocampal-entorhinal
      cortex slices.
AB  - PURPOSE: Seizure-like events (SLEs) induced by 4-aminopyridine in rat organotypic
      slices cultures, which are prepared early after birth, are resistant to standard
      antiepileptic drugs. In this study we tested the hypothesis that
      pharmacoresistance may be an intrinsic property of the immature brain. METHODS:
      Frequently recurring SLEs presumably representing status epilepticus were induced
      by 4-aminopyridine in acute rat hippocampal-entorhinal cortex slices obtained
      from postnatal day 3-19 (P3-P19), and the effects of carbamazepine, phenytoin,
      valproic acid, and phenobarbital were examined. In addition, bumetanide was
      tested, which blocks the Na(+) -K(+) -2Cl(-) (NKCC1) cotransporter, and also
      acetazolamide, which blocks the carbonic anhydrase and thereby the accumulation
      of bicarbonate inside neurons. RESULTS: The efficacy of all antiepileptic drugs
      in blocking SLEs was dependent on postnatal age, with low efficacy in P3-P5
      slices. Antiepileptic drugs suppressed SLEs more readily in the medial entorhinal
      cortex (ECm) than in the CA3. In P3-P5 slices, valproic acid and phenobarbital
      increased both tonic and clonic seizure-like activities in the CA3, whereas
      phenytoin and carbamazepine blocked tonic-like but prolonged clonic-like
      activity. In P3-P5 slices, bumetanide often blocked SLEs in the CA3, but was not
      as effective in the ECm. Like with other antiepileptic drugs, the seizure
      suppressing effects of acetazolamide increased with postnatal age. CONCLUSION: We
      conclude that pharmacoresistance may be inherent to very immature tissue and
      suggest that expression of the NKCC1 cotransporter might contribute to
      pharmacoresistance.

PMID- 21083848
TI  - Tsunami survivors' perspectives on vulnerability and vulnerability reduction:
      evidence from Koh Phi Phi Don and Khao Lak, Thailand.
AB  - This paper presents the results of primary research with 40 survivors of the 2004
      Indian Ocean tsunami in two communities: Khao Lak (n=20) and Koh Phi Phi Don
      (n=20), Thailand. It traces tsunami survivors' perceptions of vulnerability,
      determines whether residents felt that the tsunami affected different communities
      differently, identifies the populations and sub-community groups that survivors
      distinguished as being more vulnerable than others, highlights community
      generated ideas about vulnerability reduction, and pinpoints a range of
      additional vulnerability reduction actions. Tsunami survivors most consistently
      identified the 'most vulnerable' community sub-populations as women, children,
      the elderly, foreigners, and the poor. In Khao Lak, however, respondents added
      'Burmese migrants' to this list, whereas in Koh Phi Phi Don, they added 'Thai
      Muslims'. Results suggest that the two case study communities, both small,
      coastal, tourism-dominated communities no more than 100 kilometres apart, have
      differing vulnerable sub-groups and environmental vulnerabilities, requiring
      different post-disaster vulnerability reduction efforts.

PMID- 21083849
TI  - Community strategies to improve flood risk communication in the Red River Basin,
      Manitoba, Canada.
AB  - More than a decade after the 1997 Red River Flood, vulnerability to future
      flooding exists due to a lack of risk communication. This study identifies risk
      communication gaps and discusses the creation of strategies to enhance
      information-sharing, bottom-up activity and partnership development. The
      objectives were achieved using mixed methods, including interviews, a floodplain
      wide survey, and a decision-makers' risk management workshop. The results
      highlight a number of external pressures exerted by regional floodplain policies
      and procedures that restrict risk communication and affect social vulnerability
      in the rural floodplain. The failures of a top-down approach to floodplain
      management have impacted on communities' abilities to address floodplain risks,
      have amplified local risks, and have decreased community cooperation in
      floodplain management initiatives since the 1997 'Flood of the Century'.
      Recommended policies promote the establishment of community standards to
      compensate for gaps in risk communication and the development of partnerships
      between floodplain communities.

PMID- 21083850
TI  - Managing crises through organisational development: a conceptual framework.
AB  - This paper presents a synthesis of the guiding principles in crisis management in
      accordance with the four configurational imperatives (strategy, structure,
      leadership and environment) defined by Miller (1987) and outlines interventions
      in organisational development (OD) that may contribute to their achievement. The
      aim is to build a conceptual framework at the intersection of these two fields
      that could help to strengthen the resilient capabilities of individuals,
      organisations and communities to face crises. This incursion into the field of OD
      -to generate more efficient configurations of practices in crisis management-
      seems particularly fruitful considering the system-wide application of OD, based
      on open-systems theory (Burke, 2008). Various interventions proposed by OD in
      terms of human processes, structural designs and human resource management, as
      well as strategy, may help leaders, members of organisations and civil society
      apply effectively, and in a more sustainable way, the crisis management guiding
      principles defined by researchers.

PMID- 21083851
TI  - Allergic rhinitis is an extremely common problem, but prevalence rates widely
      vary between countries.

PMID- 21083852
TI  - Diagnostic value of exhaled nitric oxide in childhood asthma and allergy.
AB  - Fractional exhaled nitric oxide (FE(NO) ) has been proposed as a diagnostic test
      of asthma. We aimed to investigate in a population based birth cohort of children
      the usefulness of FE(NO) as a diagnostic tool. The 10-yr follow up of the
      Environment and Childhood Asthma Study in Oslo included 616 children
      representative of the prospective birth cohort. Both FE(NO) (single breath
      technique) and skin prick test (SPT) were measured in 331, limited at the time by
      equipment availability. Structural parental interview, spirometry, methacholine
      challenge and exercise test were performed. FE(NO) was significantly elevated in
      children with current asthma (geometric mean 9.6 (95% confidence interval (CI)
      (6.9, 13.4) p.p.b.) compared with healthy children (5.8 (5.4, 6.3) p.p.b.; p <
      0.001). FE(NO) was highest among children with current allergic asthma (asthma
      and positive SPT) (14.0 (8.9, 22.1) p.p.b.), whereas children with non-allergic
      asthma (6.1 (4.0, 9.2) p.p.b.) had comparable FE(NO) levels to healthy children
      (p = 0.99). Allergic sensitization was most closely associated with FE(NO) . A
      FE(NO) cut-off value of 20.4 p.p.b. had a high specificity (0.97), but a low
      sensitivity (0.41) and a Positive Likelihood Ratio of 16.1 for current allergic
      asthma. In the present childhood population-based study, high FE(NO) levels were
      closely associated with current allergic asthma and not with current asthma
      without allergic sensitization. Estimating the individual predictive probability
      of having asthma by use of FE(NO,) improves the diagnostic utility of the test.

PMID- 21083853
TI  - Feasibility of exhaled nitric oxide measurements at various flow rates in
      children with asthma.
AB  - Measurement of bronchial and alveolar exhaled nitric oxide (NO) levels could be
      of clinical importance for the treatment of asthma. To discriminate between
      alveolar and bronchial NO, measurements need to be assessed at various flow
      rates. To study the feasibility, linearity, and long-term repeatability of NO
      measurements at four different exhalation flow rates in children with asthma.
      Twenty-one children with moderate persistent asthma, aged 6-12 yrs, were included
      in the study. NO was measured according to the ATS/ERS guidelines, using the NIOX
      analyzer with flow restrictors of 30, 50, 100, and 200 ml/s. Duration of the
      measurements ranged from 6-10 s, depending on the flow rate. The tests were
      repeated 3 and 6 months after the first NO measurement. Feasibility of NO
      measurements at these four flow rates increased from 67% to 91% and 95% at the
      first, second and third visit, respectively. A significant learning effect was
      present. Age and lung function indices did not influence success or failure of
      the tests. At the first measurements occasions, no problems occurred during the
      NO analysis at a 100 ml/s flow rate. There was a 75-90% success rate when
      performing the test using flow rates of 30, 50, and 200 ml/s. However, repeating
      the tests resulted in a 100% success rate. Measurements were not successful if:
      (i) children ran out of air; (ii) NO concentration exceeded 200 ppb; (iii) the
      measured NO flow was unstable; and (iv) the NO plateau was not formed. This study
      showed good feasibility and linearity of NO measurements in asthmatic children of
      6 yrs and over at flow rates between 50-200 ml/s. A significant learning effect
      was present. The long-term reproducibility of alveolar and bronchial NO values
      during 6 months was moderate.

PMID- 21083854
TI  - Bacteriological safety of multi-use vials for specific immunotherapy.

PMID- 21083855
TI  - Effects of high-dose statin on the human hepatic expression of genes involved in
      carbohydrate and triglyceride metabolism.
AB  - OBJECTIVES: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase, the rate-limiting enzyme in cholesterol synthesis, lowers plasma
      cholesterol and triglyceride (TG) levels dose dependently. The aim of this study
      was to investigate the molecular mechanism(s) of this decrease in plasma TG
      levels in atorvastatin-treated subjects. RESEARCH DESIGN AND METHODS: Lipoprotein
      separation and plasma analysis of lipids, glucose and insulin were performed in
      subjects randomly assigned to placebo (n = 9) or atorvastatin (80 mg per day) (n
      = 10) for 4 weeks. Liver TG mass was determined in pooled samples. Hepatic
      expression of several genes involved in carbohydrate and TG metabolism was
      determined. RESULTS:   Atorvastatin lowered plasma levels of very low-density
      lipoprotein (VLDL) TG (~50%, P < 0.05) and liver TG mass compared to placebo.
      Except for cholesterol changes, there were no other significant differences in
      plasma lipids, glucose or insulin. However, atorvastatin reduced mRNA expression
      of sterol regulatory element-binding protein 1c (SREBP1c) (>30%, P < 0.05),
      glucokinase (~50%, P < 0.05) and angiopoietin-like protein 3 (ANGPTL3) (~25%, P <
      0.01), and induced mRNA expression of acetyl-coenzyme A carboxylase 1 (~45%, P <
      0.05) and glucose-6-phosphatase (~90%, P < 0.05) compared to placebo.
      CONCLUSIONS: Following treatment with atorvastatin, reduced ANGPTL3 mRNA
      expression may contribute to the reduced plasma levels of VLDL TG. The reduced
      liver TG mass induced by a high dosage of atorvastatin may be important for the
      treatment of patients with fatty liver.

PMID- 21083856
TI  - Early dialysis initiation and renal function trajectory.

PMID- 21083857
TI  - Molecular analysis of parasitoid linkages (MAPL): gut contents of adult
      parasitoid wasps reveal larval host.
AB  - Metamorphosing insects often have complex and poorly known life histories. In
      particular, what they feed on during their larval stages remains unknown for the
      vast majority of species, and its documentation only results from difficult and
      time-intensive field observations, rearing or dissections. Through the
      application of a DNA analysis of gut contents in adult parasitoid wasps, we were
      able to selectively sequence a diagnostic DNA marker that permitted the
      identification of the host used by these wasps during their larval stages. By
      reproducing these results in species with different life histories, we excluded
      other potential sources of host DNA, confirming that after ingestion by the
      parasitoid larva the host DNA can persist through metamorphosis in the abdominal
      contents of the adult wasp. Our discovery considerably extends the applicability
      of molecular analysis of gut contents by enabling the documentation of food used
      by insects during their larval stages and thus increasing the accuracy and
      precision of food web studies. The 24% success rate of our approach is
      surprisingly high considering the challenging context for host DNA preservation,
      and we discuss the factors possibly affecting this rate. We propose molecular
      analysis of parasitoid linkages (MAPL) as a new method to document host
      parasitoid associations at a faster pace and with unrivalled precision. Because
      of the key regulatory role of parasitoid wasps in ecosystems, which makes them
      the most commonly used biological control agents, MAPL will have immediate
      applications in both basic and applied biological sciences.

PMID- 21083858
TI  - Peroxisome metabolism and cellular aging.
AB  - The essential role of peroxisomes in fatty acid oxidation, anaplerotic
      metabolism, and hydrogen peroxide turnover is well established. Recent findings
      suggest that these and other related biochemical processes governed by the
      organelle may also play a critical role in regulating cellular aging. The goal of
      this review is to summarize and integrate into a model the evidence that
      peroxisome metabolism actually helps define the replicative and chronological age
      of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS)
      are seen as altering organelle biogenesis and function, and eliciting changes in
      the dynamic communication networks that exist between peroxisomes and other
      cellular compartments. At low levels, peroxisomal ROS activate an anti-aging
      program in the cell; at concentrations beyond a specific threshold, a pro-aging
      course is triggered.

PMID- 21083859
TI  - Fatal sepsis in a pregnant woman with pyelonephritis caused by Escherichia coli
      bearing Dr and P adhesins: diagnosis based on postmortem strain genotyping.

PMID- 21083860
TI  - Metformin should be considered in the treatment of gestational diabetes: a
      prospective randomised study.
AB  - OBJECTIVE: To examine if oral metformin is as effective as insulin in the
      prevention of fetal macrosomy in pregnancies complicated with gestational
      diabetes mellitus (GDM). DESIGN: Open-label prospective randomised controlled
      study. SETTING: Maternity outpatient clinics in a secondary and tertiary level
      hospital in Finland. SAMPLE: One hundred women with GDM who did not attain
      euglycaemia with diet. METHODS: Women were randomised to therapy with insulin (n
      = 50) or oral metformin (n = 50). MAIN OUTCOME MEASURES: Incidence of large-for
      gestational-age (LGA) infants and neonatal morbidity. RESULTS: There were no
      statistically significant differences in the incidence of LGA (8.5 versus 10.0%,
      P = 0.97), mean birthweight, mean cord artery pH or neonatal morbidity between
      the insulin and metformin groups. Fifteen (31.9%) of the 47 women randomised to
      metformin needed supplemental insulin. They were more obese (with a body mass
      index of 36 versus 30 kg/m(2), P = 0.002), had higher fasting blood glucose
      levels in an oral glucose tolerance test (6.1 versus 5.0 mmol/l, P = 0.001) and
      needed medical treatment for GDM earlier (26 versus 31 gestational weeks, P =
      0.002) than women who were normoglycemic with metformin. There was a tendency to
      a higher rate of caesarean sections in the metformin group than in the insulin
      group (RR 1.9; 95% CI 0.99-3.71). CONCLUSIONS: Metformin seems to be suitable for
      the prevention of fetal macrosomy, especially in lean or moderately overweight
      women developing GDM in late gestation. Women with considerable obesity, high
      fasting blood glucose and an early need for pharmacological treatment may be more
      suitable for insulin therapy.

PMID- 21083861
TI  - Determinants of success in treating cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To determine the important factors affecting the long-term failure
      rate of treatment for cervical intraepithelial neoplasia (CIN). DESIGN:
      Multivariate analysis of prospectively collected clinical data. SETTING:
      Colposcopy clinic in a university teaching hospital. POPULATION: A total of 2455
      consecutive women treated for CIN for the first time between 1 January 1989 and
      31 December 2004 using excisional techniques. METHODS: The data were obtained
      from a clinical database into which information had been entered prospectively.
      Data on community follow-up were obtained from the national Exeter database of
      cervical screening results. The parameters studied were age, parity, severity of
      the lesion, extent to which the lesion involved the endocervical canal, seniority
      of the surgeon, type of treatment, anaesthesia used, dimensions of the treatment
      biopsy specimen, number of treatment biopsy fragments and completeness of
      excision. MAIN OUTCOME MEASURES: High-grade post-treatment cervical disease
      detected by biopsy or cytology. RESULTS: Univariate analysis eliminated several
      potential factors and identified interactions between some factors. Multivariate
      analysis identified the grade of disease (P < 0.001) and the extent to which the
      lesion involved the endocervical canal (P =0.008) as the most important
      determinants of high-grade post-treatment disease. Of the factors which the
      surgeon could control, depth of biopsy (P =0.002) and completeness of excision (P
      = 0.007) were the most important. CONCLUSIONS: This study confirms that clear
      margins are important to reduce the failure rate of excisional treatment for CIN.
      An adequate depth of treatment is important when the lesion involves the
      endocervical canal.

PMID- 21083862
TI  - Tuberculosis in pregnancy.
AB  - Tuberculosis (TB) remains an important infection in women globally. It is
      responsible for 700 000 deaths annually and is a major contributor to maternal
      mortality. Mycobacterium tuberculosis/HIV co-infection is common in areas of high
      HIV prevalence, and may be associated with significant perinatal and maternal
      morbidity. Improved diagnosis and treatment of TB in pregnant women are important
      interventions for both maternal and child health. Controlling TB in pregnancy in
      high-prevalence areas requires a range of interventions, including active TB
      screening in pregnant women, TB preventative therapy for HIV-infected pregnant
      women, treatment of active TB and linking mothers and children to TB care
      services.

PMID- 21083863
TI  - Complications after surgery for deeply infiltrating pelvic endometriosis.
AB  - OBJECTIVE: to evaluate the complications after surgery for deep endometriosis.
      DESIGN: retrospective study. SETTING: data from the CHU Estaing database and
      patients' charts between January 1987 and December 2007. SAMPLE: all women given
      surgical treatment for deep endometriosis. METHODS: women who underwent surgery
      for deep endometriosis were reviewed for intra- and postoperative complications.
      MAIN OUTCOME MEASURES: primary outcomes were rates of intra- and postoperative
      complications. Complications were compared according to the procedure performed.
      RESULTS: a total of 568 women were included in the study, with a mean age of 32.4
      years. The mean estimated diameter of the nodule felt by vaginal examination was
      1.8 cm (ranging from 0.5 to 7 cm). Laparoscopic surgery was performed in 560
      women (98.6%), and conversion was required in 2.3%. The mean operative time was
      155 minutes. Intraoperative complications occurred in 12 women (2.1%), including
      six minor (1.05%) and six major (1.05%) complications. Postoperative
      complications developed in 79 women (13.9%), including 54 minor (9.5%) and 26
      major (4.6%) complications (one woman had both minor and major postoperative
      complications). The overall major postoperative complication rate for women who
      underwent any type of rectal surgery (shaving, excision and suture, or segmental
      resection) was 9.3% (21 out of 226), compared with only 1.5% for the other women
      (five out of 342) (P <  .01). Shaving presented less major postoperative
      complications compared with segmental resection (24 versus 6.7%; P = 0.004).
      CONCLUSIONS: surgery for deep endometriosis is feasible, but it is associated
      with major complications, especially when any type of rectal surgery must be
      performed.

PMID- 21083864
TI  - A study of progress of labour using intrapartum translabial ultrasound, assessing
      head station, direction, and angle of descent.
AB  - OBJECTIVE: Intrapartum translabial ultrasound (ITU) has the potential to
      objectively and quantitatively assess the progress of labour. The relationships
      between the different ITU parameters and their development during normal term
      labour have not been studied. DESIGN: Observational study. SETTING: University
      teaching hospital. POPULATION: Labouring women with normal term fetuses in
      cephalic presentation. METHODS: Intrapartum translabial ultrasound measurements
      for 'head station', 'head direction', and 'angle of descent' (AoD) were taken in
      50 labouring women, compared, studied for repeatability, and correlated with the
      progress of labour. MAIN OUTCOME MEASURES: Reproducibility and correlation of ITU
      parameters and their pattern of changes during labour. RESULTS: All three ITU
      parameters were clinically well reproducible. AoD and head station were
      interchangeable, and could be calculated from each other. Head station and head
      direction changed in a typical pattern along the birth canal. Time to delivery
      correlated with ITU head station. CONCLUSIONS: Intrapartum translabial ultrasound
      is a simple technique that improves the understanding of normal and abnormal
      labour, enables the objective measurement of birth progress and provides a more
      scientific basis for assessing labour.

PMID- 21083865
TI  - Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and
      oxidative stress-associated characteristics in women with minimal and mild
      endometriosis.
AB  - OBJECTIVES: To assess immunological variables, T-cell apoptosis and oxidative
      stress markers in the peripheral blood and peritoneal fluid of women with (WEN)
      and without (WWE) endometriosis. DESIGN: Observational and transverse case
      control study. SETTING: National Institute of Perinatology, Mexico City, Mexico.
      POPULATION AND SAMPLE: Peripheral blood and peritoneal fluid obtained from 30 WWE
      and 32 WEN. METHODS: Blood was drawn before surgery and peritoneal fluid was
      collected during surgery but before any surgical procedure had been carried out.
      Flow cytometry, spectrophotometry, high-performance liquid chromatography and
      multiplex immunoassay analyses were performed. MAIN OUTCOME MEASURES  Peripheral
      and peritoneal lymphocyte subpopulations (CD3(+), CD4(+) CD3(+), CD8(+) CD3(+),
      CD16(+) CD56(+), human leucocyte antigen-DR(+) CD3(+) and CD19(+)), intracellular
      CD4(+) CD3(+) and CD8(+) CD3(+) cytokine synthesis (interleukin-2 [IL-2] and
      interferon-gamma [IFN-gamma]), CD3(+) apoptosis, malondialdehyde and ascorbate
      concentrations and peritoneal cytokine concentrations. RESULTS: No differences
      were found in peripheral and peritoneal lymphocyte subsets between the groups.
      Peritoneal T lymphocytes from WEN produced less IL-2 and IFN-gamma than those
      from WWE. Peritoneal malondialdehyde concentrations were higher and ascorbate
      concentrations were lower in WEN than in WWE. Higher peritoneal concentrations of
      pro-inflammatory cytokines (IL-1beta, tumour necrosis factor-alpha and IL-6) and
      chemokines (IL-10, IL-8, eotaxin, vascular endothelial growth factor, monocyte
      chemotactic protein-1 and regulated upon activation, normal T-cell expressed, and
      secreted) and lower concentrations of IFN-gamma, IL-1 receptor antagonist and IL
      15 were found in WEN. No statistical differences were found in IL-2, IL-4, IL-12
      and IL-13 concentrations. CONCLUSION: The alterations observed in WEN were
      associated with a diminished peritoneal T helper type 1 immune response. Pro
      inflammatory, chemotactic, angiogenic and oxidative stress markers were altered
      in the peritoneal milieu of WEN. These changes appeared to contribute to the
      peritoneal immune alterations found.

PMID- 21083866
TI  - The surgical transversus abdominis plane block--a novel approach for performing
      an established technique.
AB  - Although the transversus abdominis plane (TAP) block has an established role in
      providing postoperative analgesia following caesarean section, the technique is
      not widely used by obstetric anaesthetists. The conventional TAP block is
      associated with significant technical difficulties and risk of peritoneal, hollow
      viscus and organ perforation. We report a much simpler technique in which the
      obstetric surgeon, during open surgery, is able to introduce the TAP block via an
      intra-abdominal approach, which is technically easier and also obviates the risks
      associated with the conventional TAP procedure. We believe our technique may be
      easier, safer and equally effective.

PMID- 21083867
TI  - Left ventricular function many years after recovery from pre-eclampsia.
AB  - OBJECTIVE: Epidemiological observations have shown that women with pre-eclampsia
      are at increased risk for subsequent development of cardiovascular disease. We
      evaluated maternal haemodynamics in asymptomatic women many years after pre
      eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelets)
      syndrome. DESIGN: Case-control study. SETTING: University-based department of
      obstetrics. POPULATION: Forty-eight women, 13-18 years after the affected
      pregnancy: 17 women with a history of HELLP syndrome, 14 women with a history of
      pre-eclampsia and 17 women following normal pregnancy (control group). METHODS:
      Echocardiographic examination was performed in all groups, recording the
      isovolumetric contraction time and isovolumetric relaxation time (ICT + IVRT),
      ejection time (ET), myocardial performance index (MPI), transmitral early to
      atrial filling velocity ratio (MV-E/MV-A), stroke volume (SV) and cardiac output
      (CO). MAIN OUTCOME MEASURES: Cardiac function. RESULTS: Women with previous HELLP
      syndrome showed a significantly increased MPI (0.34 versus 0.26; P = 0.008) and
      ICT + IVRT (442.16 versus 415.03; P = 0.01); MV-E/A, SV, ET and CO were not
      significantly different. Women with a history of pre-eclampsia showed a
      significantly increased MPI (0.36 versus 0.26; P = 0.006) and decreased ET (317.3
      versus 328.93; P = 0.04); ICT + IVRT, MV-E/A, SV and CO were not significantly
      different. CONCLUSION: This study confirms epidemiological observations that
      women with pre-eclampsia are at increased risk for subsequent development of
      cardiovascular disease. Many years after HELLP syndrome or pre-eclampsia,
      asymptomatic women have an increased risk for impaired cardiac function as shown
      by an increased MPI.

PMID- 21083869
TI  - Is ionic dialysance useful for early detection of vascular access dysfunction?
      Six illustrative cases.
AB  - Continuous ionic dialysance monitoring is a useful clinical tool to determine the
      dialysis dose in real time in each hemodialysis session. We followed up 49
      patients for 16 months. Six patients with a Kt reduction of >=20% in >3
      consecutive hemodialysis sessions were identified. Fistulography demonstrated
      significant stenosis in all 6 patients. Angioplasty was performed in 5 with an
      excellent angiographic result and optimal Kt levels were restored. Unexplained
      and persistent Kt reduction in patients with stable chronic kidney disease under
      hemodialysis could represent, together with an accurate vascular access
      examination, a practical and additional indirect method for the early detection
      of vascular access dysfunction. 

PMID- 21083868
TI  - Measuring placental transfusion for term births: weighing babies with cord
      intact.
AB  - OBJECTIVE: To estimate the volume and duration of placental transfusion at term.
      DESIGN: Prospective observational study. SETTING: Maternity unit in Bradford, UK.
      POPULATION: Twenty-six term births. METHODS: Babies were weighed with umbilical
      cord intact using digital scales that record an average weight every 2 seconds.
      Placental transfusion was calculated from the change in weight between birth and
      either cord clamping or when weighing stopped. Start and end weights were
      estimated using both a B-spline and inspection of graphs. Weight was converted to
      volume, 1 ml of blood weighing 1.05 g. MAIN OUTCOME MEASURES: Volume and duration
      of placental transfusion. RESULTS: Twenty-six babies were weighed. Start weights
      were difficult to determine because of artefacts in the data as the baby was
      placed on the scales and wrapped. The mean difference in weight was 116 g [95%
      confidence interval (CI), 72-160 g] using the B-spline and 87 g (95% CI, 64-110
      g) using inspection. Converting this to the mean volume of placental transfusion
      gave 110 ml (95% CI, 69-152 ml) and 83 ml (95% CI, 61-106 ml), respectively.
      Placental transfusion was usually complete by 2 minutes, but sometimes continued
      for up to 5 minutes. Based on the B-spline, placental transfusion contributed 32
      ml (95% CI, 30-33 ml) per kilogram of birth weight to blood volume, but 24 ml
      (95% CI, 19-32 ml) based on inspection. This equates to 40% (95% CI, 37-42%) and
      30% (24-40%), respectively, of total potential blood volume. CONCLUSION:
      Inspection of the graphs probably underestimates placental transfusion. For term
      infants, placental transfusion contributes between one-third and one-quarter of
      total potential blood volume at birth.

PMID- 21083870
TI  - Arteriovenous fistula: end-to-end or end-to side anastomosis?
AB  - The purpose of the present study was to compare the end-to-end (ETEa) with the
      end-to-side (ETSa) anastomosis in patients starting hemodialysis by means of
      radio-cephalic artero-venous fistulae (AVF). In our experience, we compared the
      results, as early failure (EF), late thrombosis (LT), stenosis, steal syndrome,
      and primary patency (PP), in 2 groups of hemodialysis incident patients that had
      been placed an AVF by means of ETEa or ETSa. The observation period lasted 24
      months for each of the 2 types of AVF, starting from October 2005 to September
      2007 for ETEa and from October 2007 to September 2009 for ETSa. One hundred forty
      patients were included in the present study. We have consecutively performed 99
      AVF interventions at the wrist or at the third distal of the forearm, in 70
      patients by means of ETEa and 82 AVF interventions in the same anatomical places
      in 70 patients by means of ETSa. The patients with ETEa had a mean age of 64.4 +/
      14.6 years, males were 65.8% and the age dialysis at the end of observation was
      10.4 +/- 5.7 months. Those with ETSa had a mean age of 65.9 +/- 15.5 years and
      the males were 62.9%, the age dialysis at the end of observation was 9.2 +/- 5.5
      months. The surgical team was composed by the same nephrologists. The statistical
      study was performed by means of the chi chi-square and Fisher's exact test. We
      have observed more late thrombosis (10% vs. 4.1%) and stenosis (21.4% vs. 2.7%)
      in ETEa than in ETSa. The number of early thrombosis was similar in the 2 types
      of anastomosis. The primary patency 1-year rate was better though not
      significantly in the ETS (80% vs. 85.7%) In our experience the ETSa provides,
      overall better results, both regarding the complications and primary survival
      than ETEa. For the benefits that seem to come from it, we believe, that a broad
      ETSa in the distal native AVF is preferable to the ETEa. 

PMID- 21083871
TI  - Demographic consequences of adult sex ratio in a reintroduced hihi population.
AB  - 1. Male-biased adult sex ratios are frequently observed in free-ranging
      populations and are known to cause changes in mating behaviours including
      increased male harassment of females, which can cause injury to females and/or
      alter female behaviour during breeding. 2. Although we can explain why such
      behaviours may evolve and have studied their impacts on individuals when it does,
      we know very little about the demographic consequences of harassment caused by
      changes in adult sex ratio. 3. Using a 12-year longitudinal data set of a free
      living and endangered New Zealand passerine, the hihi (Notiomystis cincta), we
      show that a changing adult sex ratio has little or no effect on adult female
      survival or the number of fledglings produced per female. This is despite clear
      evidence of male harassment of breeding females when the sex ratio was male
      biased (up to three males per female). 4. The length of the study and major
      fluctuations in sex ratio observed made it possible to obtain narrow confidence
      or credible intervals for effect sizes, showing that any effect of sex ratio on
      demographic rates were small. 5. Our results provide rare empirical evidence for
      the demographic consequences of biased adult sex ratios in the wild and
      particularly in a conservation context.

PMID- 21083873
TI  - Fulminant mediastinitis after goiter recurrence surgery: a case report.
AB  - INTRODUCTION: Necrotizing soft tissue infection is a life-threatening disease
      characterized by rapid progressive inflammation and necrosis of the subcutaneous
      and deep fascia with or without involvement of the adjacent muscles. CASE
      PRESENTATION: We report the case of a 62-year-old Caucasian woman with goiter
      recurrence who underwent a right-sided hemithyroidectomy. Postoperatively, she
      developed fulminant mediastinitis caused by group A beta-hemolytic streptococcus
      and septic shock. Our patient survived this rare life-threatening complication.
      CONCLUSIONS: Initial atypical postoperative symptoms, such as personality changes
      or an unstable circulatory system, should lead a practitioner to consider the
      possibility of this severe complication and to begin therapy immediately.

PMID- 21083875
TI  - Tamsulosin-induced severe hypotension during general anesthesia: a case report.
AB  - INTRODUCTION: Tamsulosin, a selective alpha1-adrenergic receptor (alpha1-AR)
      antagonist, is a widely prescribed first-line agent for benign prostatic
      hypertrophy (BPH). Its interaction with anesthetic agents has not been described.
      CASE PRESENTATION: We report the case of 54-year-old Asian man undergoing
      elective left thyroid lobectomy. The only medication the patient was taking was
      tamsulosin 0.4 mg for the past year for BPH. He developed persistent hypotension
      during the maintenance phase of anesthesia while receiving oxygen, nitrous oxide
      and 1% isoflurane. The hypotension could have been attributable to a possible
      interaction between inhalational anesthetic and tamsulosin. CONCLUSION: Vigilance
      for unexpected hypotension is important in surgical patients who are treated with
      selective alpha1-AR blockers. If hypotension occurs, vasopressors that act
      directly on adrenergic receptors could be more effective.

PMID- 21083874
TI  - Travel and migration associated infectious diseases morbidity in Europe, 2008.
AB  - BACKGROUND: Europeans represent the majority of international travellers and
      clinicians encountering returned patients have an essential role in recognizing,
      and communicating travel-associated public health risks. METHODS: To investigate
      the morbidity of travel associated infectious diseases in European travellers, we
      analysed diagnoses with demographic, clinical and travel-related predictors of
      disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet
      centres with a presumed travel associated condition. RESULTS: Gastro-intestinal
      (GI) diseases accounted for 33% of illnesses, followed by febrile systemic
      illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%).
      There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis,
      a dengue shock syndrome and a Plasmodium falciparum malaria.GI conditions
      included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis
      (2.3%). Among febrile systemic illnesses with identified pathogens, malaria
      (5.4%) accounted for most cases followed by dengue (1.9%) and others including
      chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus
      infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological
      conditions were dominated by bacterial infections, arthropod bites, cutaneous
      larva migrans and animal bites requiring rabies post-exposure prophylaxis and
      also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory
      illness included 112 cases of tuberculosis including cases of multi-drug
      resistant or extensively drug resistant tuberculosis, 104 cases of influenza like
      illness, and 5 cases of Legionnaires disease. Sexually transmitted infections
      (STI) accounted for 0.6% of total diagnoses and included HIV infection and
      syphilis. A total of 165 cases of potentially vaccine preventable diseases were
      reported. Purpose of travel and destination specific risk factors was identified
      for several diagnoses such as Chagas disease in immigrant travellers from South
      America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel
      within Europe was also associated with health risks with distinctive profiles for
      Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel
      associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied
      according to regions visited by ill travellers. The spectrum of travel associated
      morbidity also shows that there is a need to dispel the misconception that
      travel, close to home, in Europe, is without significant health risk.

PMID- 21083877
TI  - Half a pack of cigarettes a day more than doubles DNA breaks in circulating
      leukocytes.
AB  - BACKGROUND: The mechanisms by which smoking induces damage is not known for all
      diseases. One mechanism believed to play a role is oxidative stress. Oxidative
      stress leads to cellular damage including DNA damage, particularly DNA breaks. We
      conducted this study to test the hypothesis that smokers have increased DNA
      breaks in their circulating leukocytes. METHODS: A comparative quantification of
      single-stranded DNA breaks was performed by comet assay analysis in the
      circulating leukocytes of ten healthy smokers (average smoking rate: half a pack
      a day, range: 9-12 cigarettes a day) and ten age and sex matched healthy non
      smokers. DNA breaks lead to smaller pieces of DNA, which migrate out of the
      nucleus forming a tail during gel-electrophoresis. Damage of an individual cell
      was quantified by the parameters tail moment and olive moment. RESULTS: Smoking
      had a clear effect on both study parameters (tail and olive moment). Smokers had
      more than double the amount of ss-DNA breaks in their circulating leukocytes than
      non-smokers [tail moment: 0.75 AU [smokers] compared to 0.2 AU [non-smokers];
      olive moment: 0.85 AU [smokers] compared to 0.3 AU [non-smokers]; both p <
      0.001]. CONCLUSION: Smoking half a pack a day interferes with DNA integrity. One
      potential explanation for the enhanced DNA breaks in smokers is oxidative stress.

PMID- 21083876
TI  - Antidiarrhoea and toxicological evaluation of the leaf extract of Dissotis
      rotundifolia Triana (Melastomataceae).
AB  - BACKGROUND: The leaves of Dissotis rotundifolia are used ethnomedically across
      Africa without scientific basis or safety concerns. Determination of its
      phytochemical constituents, antimicrobial activity, effects on the
      gastrointestinal tract (GIT) as well as toxicological profile will provide
      supportive scientific evidence in favour of its continous usage. METHOD: Chemical
      and chromatographic tests were employed in phytochemical investigations.
      Inhibitory activity against clinical strains of Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus and Salmonella typhi were compared with
      Gentamycin. Our report includes minimum inhibitory concentration (MIC) against
      the tested organisms. The effect of the ethanol extract on the motility of the
      GIT in mice using the charcoal plug method and castor oil induced diarrhoea in
      rats was evaluated. Toxicological evaluation was determined by administering 250
      mg/kg and 500 mg/kg of extracts on male Wistar rats for 14 days with normal
      saline as control. The tissues of the kidneys, liver, heart and testes were
      examined. RESULTS: Phytochemical studies revealed the presence of alkaloids,
      saponin and cardiac glycosides. The crude ethanol extract and fractions inhibited
      the growth of E. coli, P. aeruginosa, S. aureus and S. typhi to varying extents.
      The degree of transition exhibited by the charcoal meal was dose-dependent. In
      the castor oil induced diarrhoea test, all the doses showed anti-spasmodic
      effects. The LD50 in mice was above 500 mg/kg body weight. Toxicological
      evaluation at 500 mg/kg showed increased cytoplasmic eosinophilia and densely
      stained nuclei of the liver, tubular necrosis of the kidney, presence of ill
      defined testes with indistinct cell outlines and no remarkable changes in the
      heart. CONCLUSION: Ethanol extracts of Dissotis rotundifolia have demonstrated
      antimicrobial activity against clinical strains of selected microorganisms. The
      plant showed potential for application in the treatment of diarrhoea, thereby
      justifying its usage across Africa. It also demonstrated toxicity in certain
      organs at the dose of 500 mg/kg, and it will be necessary to fully establish its
      safety profile.

PMID- 21083878
TI  - Thoracoscopic-assisted repair of a bochdalek hernia in an adult: a case report.
AB  - INTRODUCTION: Bochdalek hernia is a congenital defect of the diaphragm that
      usually presents in the neonatal period with life-threatening cardiorespiratory
      distress. It is rare for Bochdalek hernias to remain silent until adulthood. Once
      a Bochdalek hernia has been diagnosed, surgical treatment is necessary to avoid
      complications such as perforation and necrosis. CASE PRESENTATION: We present a
      17-year-old Japanese boy with left-upper-quadrant pain for two months. Chest
      radiography showed an elevated left hemidiaphragm. Computed tomography revealed a
      congenital diaphragmatic hernia. The spleen and left colon had been displaced
      into the left thoracic cavity through a left posterior diaphragmatic defect. We
      diagnosed a Bochdalek hernia. Surgical treatment was performed via a
      thoracoscopic approach. The boy was placed in the reverse Trendelenburg position
      and intrathoracic pressure was increased by CO2 gas insufflations. This is a very
      useful procedure for reducing herniated contents and we were able to place the
      herniated organs safely back in the peritoneal cavity. The diaphragmatic defect
      was too large to close with thoracoscopic surgery alone. Small incision
      thoracotomy was required and primary closure was performed. His postoperative
      course was uneventful and there has been no recurrence of the diaphragmatic
      hernia to date. CONCLUSION: Thoracoscopic surgery, performed with the boy in the
      reverse Trendelenburg position and using CO2 gas insufflations in the thoracic
      cavity, was shown to be useful for Bochdalek hernia repair.

PMID- 21083879
TI  - Necrotising fasciitis of the shoulder in association with rheumatoid arthritis
      treated with etanercept: a case report.
AB  - INTRODUCTION: Necrotising fasciitis is a severe infection characterised by the
      fulminant destruction of tissue with associated systemic signs of sepsis and
      toxicity. Etanercept is a fully human fusion protein that inhibits tumor necrosis
      factor and the inflammatory cascade. It is effective in the treatment of many
      disorders but concerns regarding severe life threatening infections have been
      raised in multiple reports. CASE PRESENTATION: We present the case of a 39-year
      old Caucasian man, who presented with sudden onset of severe and progressive neck
      and left shoulder pain, with a two-year history of seronegative rheumatoid
      arthritis treated with azathoprine and etanercept. On examination the left side
      of his neck and his left shoulder were oedematous, tender with an erythematous
      rash and his active range of movement was limited. Magnetic resonance imaging of
      his shoulder showed extensive oedema of the subcutaneous and intramuscular fat of
      the left lower neck consistent with fasciitis. He was treated medically and made
      a good recovery. CONCLUSION: Our patient, while having a pre-existing increased
      mortality risk, had a serious infection which responded well to optimum medical
      treatment without the need for surgery. As anti tumor necrosis factor agents are
      frequently associated with infection, including tuberculous infection, this case
      highlights the need for a high index of suspicion for other severe bacterial
      infections in patients on immunosuppressants.

PMID- 21083880
TI  - Cost-effectiveness of monitoring glaucoma patients in shared care: an economic
      evaluation alongside a randomized controlled trial.
AB  - BACKGROUND: Population aging increases the number of glaucoma patients which
      leads to higher workloads of glaucoma specialists. If stable glaucoma patients
      were monitored by optometrists and ophthalmic technicians in a glaucoma follow-up
      unit (GFU) rather than by glaucoma specialists, the specialists' workload and
      waiting lists might be reduced.We compared costs and quality of care at the GFU
      with those of usual care by glaucoma specialists in the Rotterdam Eye Hospital
      (REH) in a 30-month randomized clinical trial. Because quality of care turned out
      to be similar, we focus here on the costs. METHODS: Stable glaucoma patients were
      randomized between the GFU and the glaucoma specialist group. Costs per patient
      year were calculated from four perspectives: those of patients, the Rotterdam Eye
      Hospital (REH), Dutch healthcare system, and society. The outcome measures were:
      compliance to the protocol; patient satisfaction; stability according to the
      practitioner; mean difference in IOP; results of the examinations; and number of
      treatment changes. RESULTS: Baseline characteristics (such as age, intraocular
      pressure and target pressure) were comparable between the GFU group (n = 410) and
      the glaucoma specialist group (n = 405).Despite a higher number of visits per
      year, mean hospital costs per patient year were lower in the GFU group (?139 vs.
      ?161). Patients' time and travel costs were similar. Healthcare costs were
      significantly lower for the GFU group (?230 vs. ?251), as were societal costs
      (?310 vs. ?339) (p < 0.01). Bootstrap-, sensitivity- and scenario-analyses showed
      that the costs were robust when varying hospital policy and the duration of
      visits and tests. CONCLUSION: We conclude that this GFU is cost-effective and
      deserves to be considered for implementation in other hospitals.

PMID- 21083881
TI  - Patients with ovarian carcinoma excrete different altered levels of urine CD59,
      kininogen-1 and fragments of inter-alpha-trypsin inhibitor heavy chain H4 and
      albumin.
AB  - BACKGROUND: Diagnosis of ovarian carcinoma is in urgent need for new
      complementary biomarkers for early stage detection. Proteins that are aberrantly
      excreted in the urine of cancer patients are excellent biomarker candidates for
      development of new noninvasive protocol for early diagnosis and screening
      purposes. In the present study, urine samples from patients with ovarian
      carcinoma were analysed by two-dimensional gel electrophoresis and the profiles
      generated were compared to those similarly obtained from age-matched cancer
      negative women. RESULTS: Significant reduced levels of CD59, kininogen-1 and a 39
      kDa fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), and
      enhanced excretion of a 19 kDa fragment of albumin, were detected in the urine of
      patients with ovarian carcinoma compared to the control subjects. The different
      altered levels of the proteins were confirmed by Western blotting using antisera
      and a lectin that bind to the respective proteins. CONCLUSION: CD59, kininogen-1
      and fragments of ITIH4 and albumin may be used as complementary biomarkers in the
      development of new noninvasive protocols for diagnosis and screening of ovarian
      carcinoma.

PMID- 21083882
TI  - Omental infarction in the postpartum period: a case report and a review of the
      literature.
AB  - INTRODUCTION: Omental infarction is a rare and often misdiagnosed clinical event
      with unspecific symptoms. It affects predominantly young and middle aged women.
      CASE PRESENTATION: This is a case report of a 26-year-old Caucasian woman with
      spontaneous omental infarction two weeks after normal vaginal delivery.
      CONCLUSION: Omental infarction is a differential diagnosis in the postpartum
      acute abdomen. As some cases of omental infarction, which are caused by torsion,
      can be adequately diagnosed via computed tomography, a conservative treatment
      strategy for patients without complications should be considered in order to
      avoid any unnecessary surgical intervention.

PMID- 21083883
TI  - An option for measuring maternal mortality in developing countries: a survey
      using community informants.
AB  - BACKGROUND: The maternal mortality ratio (MMR) remains high in most developing
      countries. Local, recent estimates of MMR are needed to motivate policymakers and
      evaluate interventions. But, estimating MMR, in the absence of vital registration
      systems, is difficult. This paper describes an efficient approach using village
      informant networks to capture maternal death cases (Maternal Deaths from
      Informants/Maternal Death Follow on Review or MADE-IN/MADE-FOR) developed to
      address this gap, and examines its validity and efficiency. METHODS: MADE-IN used
      two village informant networks - heads of neighbourhood units (RTs) and health
      volunteers (Kaders). Informants were invited to attend separate network meetings 
      through the village head (for the RT) and through health centre for the kaders.
      Attached to the letter was a form with written instructions requesting informants
      list deaths of women of reproductive age (WRA) in the village during the previous
      two years. At a 'listing meeting' the informants' understanding on the form was
      checked, informants could correct their forms, and then collectively agreed a
      consolidated list. MADE-FOR consisted of visits relatives of likely pregnancy
      related deaths (PRDs) identified from MADE-IN, to confirm the PRD status and
      gather information about the cause of death. Capture-recapture (CRC) analysis
      enabled estimation of coverage rates of the two networks, and of total PRDs.
      RESULTS: The RT network identified a higher proportion of PRDs than the kaders
      (estimated 0.85 vs. 0.71), but the latter was easier and cheaper to access.
      Assigned PRD status amongst identified WRA deaths was more accurate for the kader
      network, and seemingly for more recent deaths, and for deaths from rural areas.
      Assuming information on live births from an existing source to calculate the MMR,
      MADE-IN/MADE-FOR cost only $0.1 (US) per women-year risk of exposure,
      substantially cheaper than alternatives. CONCLUSIONS: This study shows that
      reliable local, recent estimates of MMR can be obtained relatively cheaply using
      two independent informant networks to identify cases. Neither network captured
      all PRDs, but capture-recapture analysis allowed self-calibration. However, it
      requires careful avoidance of false-positives, and matching of cases identified
      by both networks, which was achieved by the home visit.

PMID- 21083884
TI  - An initial comparative map of copy number variations in the goat (Capra hircus)
      genome.
AB  - BACKGROUND: The goat (Capra hircus) represents one of the most important farm
      animal species. It is reared in all continents with an estimated world population
      of about 800 million of animals. Despite its importance, studies on the goat
      genome are still in their infancy compared to those in other farm animal species.
      Comparative mapping between cattle and goat showed only a few rearrangements in
      agreement with the similarity of chromosome banding. We carried out a cross
      species cattle-goat array comparative genome hybridization (aCGH) experiment in
      order to identify copy number variations (CNVs) in the goat genome analysing
      animals of different breeds (Saanen, Camosciata delle Alpi, Girgentana, and
      Murciano-Granadina) using a tiling oligonucleotide array with ~385,000 probes
      designed on the bovine genome. RESULTS: We identified a total of 161 CNVs (an
      average of 17.9 CNVs per goat), with the largest number in the Saanen breed and
      the lowest in the Camosciata delle Alpi goat. By aggregating overlapping CNVs
      identified in different animals we determined CNV regions (CNVRs): on the whole,
      we identified 127 CNVRs covering about 11.47 Mb of the virtual goat genome
      referred to the bovine genome (0.435% of the latter genome). These 127 CNVRs
      included 86 loss and 41 gain and ranged from about 24 kb to about 1.07 Mb with a
      mean and median equal to 90,292 bp and 49,530 bp, respectively. To evaluate
      whether the identified goat CNVRs overlap with those reported in the cattle
      genome, we compared our results with those obtained in four independent cattle
      experiments. Overlapping between goat and cattle CNVRs was highly significant (P
      < 0.0001) suggesting that several chromosome regions might contain recurrent
      interspecies CNVRs. Genes with environmental functions were over-represented in
      goat CNVRs as reported in other mammals. CONCLUSIONS: We describe a first map of
      goat CNVRs. This provides information on a comparative basis with the cattle
      genome by identifying putative recurrent interspecies CNVs between these two
      ruminant species. Several goat CNVs affect genes with important biological
      functions. Further studies are needed to evaluate the functional relevance of
      these CNVs and their effects on behavior, production, and disease resistance
      traits in goats.

PMID- 21083885
TI  - Reconstruction and analysis of genome-scale metabolic model of a photosynthetic
      bacterium.
AB  - BACKGROUND: Synechocystis sp. PCC6803 is a cyanobacterium considered as a
      candidate photo-biological production platform--an attractive cell factory
      capable of using CO2 and light as carbon and energy source, respectively. In
      order to enable efficient use of metabolic potential of Synechocystis sp.
      PCC6803, it is of importance to develop tools for uncovering stoichiometric and
      regulatory principles in the Synechocystis metabolic network. RESULTS: We report
      the most comprehensive metabolic model of Synechocystis sp. PCC6803 available,
      iSyn669, which includes 882 reactions, associated with 669 genes, and 790
      metabolites. The model includes a detailed biomass equation which encompasses
      elementary building blocks that are needed for cell growth, as well as a detailed
      stoichiometric representation of photosynthesis. We demonstrate applicability of
      iSyn669 for stoichiometric analysis by simulating three physiologically relevant
      growth conditions of Synechocystis sp. PCC6803, and through in silico metabolic
      engineering simulations that allowed identification of a set of gene knock-out
      candidates towards enhanced succinate production. Gene essentiality and hydrogen
      production potential have also been assessed. Furthermore, iSyn669 was used as a
      transcriptomic data integration scaffold and thereby we found metabolic hot-spots
      around which gene regulation is dominant during light-shifting growth regimes.
      CONCLUSIONS: iSyn669 provides a platform for facilitating the development of
      cyanobacteria as microbial cell factories.

PMID- 21083886
TI  - Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a
      prospective observational study.
AB  - INTRODUCTION: Guidelines recommend that two blood cultures be performed in
      patients with febrile urinary tract infection (UTI), to detect bacteremia and
      help diagnose urosepsis. The usefulness and cost-effectiveness of this practice
      have been criticized. This study aimed to evaluate clinical characteristics and
      the biomarker procalcitonin (PCT) as an aid in predicting bacteremia. METHODS: A
      prospective observational multicenter cohort study included consecutive adults
      with febrile UTI in 35 primary care units and 8 emergency departments of 7
      regional hospitals. Clinical and microbiological data were collected and PCT and
      time to positivity (TTP) of blood culture were measured. RESULTS: Of 581
      evaluable patients, 136 (23%) had bacteremia. The median age was 66 years
      (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three
      different models: a clinical model including seven bed-side characteristics, the
      clinical model plus PCT, and a PCT only model. The diagnostic abilities of these
      models as reflected by area under the curve of the receiver operating
      characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95%
      CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating
      corresponding sensitivity and specificity for the presence of bacteremia after
      each step of adding a significant predictor in the model yielded that the PCT >
      0.25 MUg/l only model had the best diagnostic performance (sensitivity 0.95; 95%
      CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single
      decision tool, this would result in 40% fewer blood cultures being taken, while
      still identifying 94 to 99% of patients with bacteremia.The TTP of E. coli
      positive blood cultures was linearly correlated with the PCT log value; the
      higher the PCT the shorter the TTP (R(2) = 0.278, P = 0.007). CONCLUSIONS: PCT
      accurately predicts the presence of bacteremia and bacterial load in patients
      with febrile UTI. This may be a helpful biomarker to limit use of blood culture
      resources.

PMID- 21083887
TI  - Contribution of constitutively proliferating precursor cell subtypes to dentate
      neurogenesis after cortical infarcts.
AB  - BACKGROUND: It is well known that focal ischemia increases neurogenesis in the
      adult dentate gyrus of the hippocampal formation but the cellular mechanisms
      underlying this proliferative response are only poorly understood. We here
      investigated whether precursor cells which constitutively proliferate before the
      ischemic infarct contribute to post-ischemic neurogenesis. To this purpose,
      transgenic mice expressing green fluorescent protein (GFP) under the control of
      the nestin promoter received repetitive injections of the proliferation marker
      bromodeoxyuridine (BrdU) prior to induction of cortical infarcts. We then
      immunocytochemically analyzed the fate of these BrdU-positive precursor cell
      subtypes from day 4 to day 28 after the lesion. RESULTS: Quantification of BrdU
      expressing precursor cell populations revealed no alteration in number of radial
      glia-like type 1 cells but a sequential increase of later precursor cell subtypes
      in lesioned animals (type 2a cells at day 7, type 3 cells/immature neurons at day
      14). These alterations result in an enhanced survival of mature neurons 4 weeks
      postinfarct. CONCLUSIONS: Focal cortical infarcts recruit dentate precursor cells
      generated already before the infarct and significantly contribute to an enhanced
      neurogenesis. Our findings thereby increase our understanding of the complex
      cellular mechanisms of postlesional neurogenesis.

PMID- 21083888
TI  - Apoptosis induced by parasitic diseases.
AB  - Fatalities caused by parasitic infections often occur as a result of tissue
      injury that results from a form of host-cell death known as apoptosis. However,
      instead of being pathogenic, parasite-induced apoptosis may facilitate host
      survival. Consequently, it is of utmost importance to decipher and understand the
      process and the role of apoptosis induced or controlled by parasites in humans.
      Despite this, few studies provide definitive knowledge of parasite-induced host
      cell apoptosis. Here, the focus is on a consideration of host-cell apoptosis as
      either a pathogenic feature or as a factor enabling parasite survival and
      development.Cell death by apoptotic-like mechanisms could be described as a ride
      to death with a return ticket, as initiation of the pathway may be reversed, with
      the potential that it could be manipulated for therapeutic purposes. The
      management of host-cell apoptosis could thus be an adjunctive factor for
      parasitic disease treatment. Evidence that the apoptotic process could be
      reversed by anti-apoptotic drugs has recently been obtained, leading to the
      possibility of host-cell rescue after injury. An important issue will be to
      predict the beneficial or deleterious effects of controlling human cell death by
      apoptotic-like mechanisms during parasitic diseases.

PMID- 21083889
TI  - Association of serum markers with improvement in clinical response measures after
      treatment with golimumab in patients with active rheumatoid arthritis despite
      receiving methotrexate: results from the GO-FORWARD study.
AB  - INTRODUCTION: The goal of this study was to identify serum markers that are
      modulated by treatment with golimumab with or without methotrexate (MTX) and are
      associated with clinical response. METHODS: Sera were collected at weeks 0 and 4
      from a total of 336 patients (training dataset, n = 100; test dataset, n = 236)
      from the GO-FORWARD study of patients with active rheumatoid arthritis despite
      MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100
      mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX.
      Subcutaneous injections were administered every 4 weeks. Samples were tested for
      select inflammatory, bone, and cartilage markers and for protein profiling using
      multianalyte profiles. RESULTS: Treatment with golimumab with or without MTX
      resulted in significant decreases in a variety of serum proteins at week 4 as
      compared with placebo plus MTX. The American College of Rheumatology (ACR) 20,
      ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct
      biomarker profile compared with nonresponding patients. CONCLUSIONS: ACR 20 and
      ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a
      distinct change from baseline to week 4 in serum protein profile as compared with
      nonresponders. Some of these changed markers were also associated with multiple
      clinical response measures and improvement in outcome measures in
      golimumab/golimumab + MTX-treated patients. Although the positive and negative
      predictive values of the panel of markers were modest, they were stronger than C
      reactive protein alone in predicting clinical response to golimumab. TRIAL
      REGISTRATION: http://ClinicalTrials.gov identification number: NCT00264550.

PMID- 21083890
TI  - Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated
      neurocognitive disorder: a cross-sectional cohort study.
AB  - BACKGROUND: Neuroinflammation and demyelination have been suggested as mechanisms
      causing HIV-1 associated neurocognitive disorder (HAND). This cross-sectional
      cohort study explores the potential role of antibodies to myelin oligodendrocyte
      glycoprotein (MOG), a putative autoantigen in multiple sclerosis, in the
      pathogenesis of HAND. METHODS: IgG antibodies against MOG were measured by ELISA
      in sera and cerebrospinal fluid (CSF) of 65 HIV-positive patients with HAND (n =
      14), cerebral opportunistic infections (HIVOI, n = 25), primary HIV infection
      (HIVM, n = 5) and asymptomatic patients (HIVasy, n = 21). As control group HIV
      negative patients with bacterial or viral CNS infections (OIND, n = 18) and other
      neurological diseases (OND, n = 22) were included. In a subset of HAND patients
      MOG antibodies were determined before and during antiviral therapy. RESULTS: In
      serum, significantly higher MOG antibody titers were observed in HAND compared to
      OND patients. In CSF, significantly higher antibody titers were observed in HAND
      and HIVOI patients compared to HIVasy and OND patients and in OIND compared to
      OND patients. CSF anti-MOG antibodies showed a high sensitivity and specificity
      (85.7% and 76.2%) for discriminating patients with active HAND from asymptomatic
      HIV patients. MOG immunopositive HAND patients performed significantly worse on
      the HIV dementia scale and showed higher viral load in CSF. In longitudinally
      studied HAND patients, sustained antibody response was noted despite successful
      clearance of viral RNA. CONCLUSIONS: Persistence of MOG antibodies despite viral
      clearance in a high percentage of HAND patients suggests ongoing
      neuroinflammation, possibly preventing recovery from HAND.

PMID- 21083891
TI  - Targeting essential pathways in trypanosomatids gives insights into protozoan
      mechanisms of cell death.
AB  - Apoptosis is a normal component of the development and health of multicellular
      organisms. However, apoptosis is now considered a prerogative of unicellular
      organisms, including the trypanosomatids of the genera Trypanosoma spp. and
      Leishmania spp., causative agents of some of the most important neglected human
      diseases. Trypanosomatids show typical hallmarks of apoptosis, although they lack
      some of the key molecules contributing to this process in metazoans, like caspase
      genes, Bcl-2 family genes and the TNF-related family of receptors. Despite the
      lack of these molecules, trypanosomatids appear to have the basic machinery to
      commit suicide. The components of the apoptotic execution machinery of these
      parasites are slowly coming into light, by targeting essential processes and
      pathways with different apoptogenic agents and inhibitors. This review will be
      confined to the events known to drive trypanosomatid parasites to apoptosis.

PMID- 21083893
TI  - Influence of inverse dynamics methods on the calculation of inter-segmental
      moments in vertical jumping and weightlifting.
AB  - BACKGROUND: A vast number of biomechanical studies have employed inverse dynamics
      methods to calculate inter-segmental moments during movement. Although all
      inverse dynamics methods are rooted in classical mechanics and thus theoretically
      the same, there exist a number of distinct computational methods. Recent research
      has demonstrated a key influence of the dynamics computation of the inverse
      dynamics method on the calculated moments, despite the theoretical equivalence of
      the methods. The purpose of this study was therefore to explore the influence of
      the choice of inverse dynamics on the calculation of inter-segmental moments.
      METHODS: An inverse dynamics analysis was performed to analyse vertical jumping
      and weightlifting movements using two distinct methods. The first method was the
      traditional inverse dynamics approach, in this study characterized as the 3 step
      method, where inter-segmental moments were calculated in the local coordinate
      system of each segment, thus requiring multiple coordinate system
      transformations. The second method (the 1 step method) was the recently proposed
      approach based on wrench notation that allows all calculations to be performed in
      the global coordinate system. In order to best compare the effect of the inverse
      dynamics computation a number of the key assumptions and methods were harmonized,
      in particular unit quaternions were used to parameterize rotation in both methods
      in order to standardize the kinematics. RESULTS: Mean peak inter-segmental
      moments calculated by the two methods were found to agree to 2 decimal places in
      all cases and were not significantly different (p > 0.05). Equally the normalized
      dispersions of the two methods were small. CONCLUSIONS: In contrast to previously
      documented research the difference between the two methods was found to be
      negligible. This study demonstrates that the 1 and 3 step method are
      computationally equivalent and can thus be used interchangeably in
      musculoskeletal modelling technology. It is important that future work clarifies
      the influence of the other inverse dynamics methods on the calculation of inter
      segmental moments. Equally future work is needed to explore the sensitivity of
      kinematics computations to the choice of rotation parameterization.

PMID- 21083892
TI  - Revisiting HIV-1 uncoating.
AB  - HIV uncoating is defined as the loss of viral capsid that occurs within the
      cytoplasm of infected cells before entry of the viral genome into the nucleus. It
      is an obligatory step of HIV-1 early infection and accompanies the transition
      between reverse transcription complexes (RTCs), in which reverse transcription
      occurs, and pre-integration complexes (PICs), which are competent to integrate
      into the host genome. The study of the nature and timing of HIV-1 uncoating has
      been paved with difficulties, particularly as a result of the vulnerability of
      the capsid assembly to experimental manipulation. Nevertheless, recent studies of
      capsid structure, retroviral restriction and mechanisms of nuclear import, as
      well as the recent expansion of technical advances in genome-wide studies and
      cell imagery approaches, have substantially changed our understanding of HIV
      uncoating. Although early work suggested that uncoating occurs immediately
      following viral entry in the cell, thus attributing a trivial role for the capsid
      in infected cells, recent data suggest that uncoating occurs several hours later
      and that capsid has an all-important role in the cell that it infects: for
      transport towards the nucleus, reverse transcription and nuclear import. Knowing
      that uncoating occurs at a later stage suggests that the viral capsid interacts
      extensively with the cytoskeleton and other cytoplasmic components during its
      transport to the nucleus, which leads to a considerable reassessment of our
      efforts to identify potential therapeutic targets for HIV therapy. This review
      discusses our current understanding of HIV uncoating, the functional interplay
      between infectivity and timely uncoating, as well as exposing the appropriate
      methods to study uncoating and addressing the many questions that remain
      unanswered.

PMID- 21083894
TI  - Ambulatory health services utilization in patients with dementia - Is there an
      urban-rural difference?
AB  - BACKGROUND: Due to demographic changes and an un-equal distribution of
      physicians, regional analyses of service utilization of elderly patients are
      crucial, especially for diseases with an impact like dementia. This paper focuses
      on dementia patients. The aim of the study is to identify differences in service
      utilization of incident dementia patients in urban and rural areas. METHODS:
      Basis for the analysis were all insured persons of a German Health Insurance fund
      (the GEK) aged 65 years and older living in rural and urban areas. We focussed on
      physician contacts in the outpatient sector during the first year after an
      incidence diagnosis of dementia. Special attention was given to contacts with
      primary care physicians and neurologists/psychiatrists. The dementia cohort was
      analyzed together with a non-dementia control group drawn according to age,
      gender and amount of physician contacts. Uni- and bivariate as well as
      multivariate analysis were performed to estimate the influences on service
      utilization. RESULTS: Results show that the provision of primary care seems to be
      equally given in urban and rural areas. For specialists contacts however, rural
      patients are less likely to consult neurologists or psychiatrists. This trend can
      already be seen before the incident diagnosis of dementia. All consultations rise
      in the quarter of the incident dementia diagnosis compared to the control group.
      The results were also tested in a linear and a logistic regression, showing a
      higher chance for persons living in urban areas to visit a specialist and an
      overall higher rate in service utilization for dementia patients. CONCLUSIONS:
      Because of a probable increase in the number of dementia patients, service
      provision has to be accessible even in rural areas. Due to this and the fact that
      demographic change is happening at different paces in different regions, regional
      variations have to be considered to ensure the future service provision.

PMID- 21083895
TI  - Reliability and validity of the Japanese version of the Resilience Scale and its
      short version.
AB  - BACKGROUND: The clinical relevance of resilience has received considerable
      attention in recent years. The aim of this study is to demonstrate the
      reliability and validity of the Japanese version of the Resilience Scale (RS) and
      short version of the RS (RS-14). FINDINGS: The original English version of RS was
      translated to Japanese and the Japanese version was confirmed by back
      translation. Participants were 430 nursing and university psychology students.
      The RS, Center for Epidemiologic Studies Depression Scale (CES-D), Rosenberg Self
      Esteem Scale (RSES), Social Support Questionnaire (SSQ), Perceived Stress Scale
      (PSS), and Sheehan Disability Scale (SDS) were administered. Internal
      consistency, convergent validity and factor loadings were assessed at initial
      assessment. Test-retest reliability was assessed using data collected from 107
      students at 3 months after baseline. Mean score on the RS was 111.19. Cronbach's
      alpha coefficients for the RS and RS-14 were 0.90 and 0.88, respectively. The
      test-retest correlation coefficients for the RS and RS-14 were 0.83 and 0.84,
      respectively. Both the RS and RS-14 were negatively correlated with the CES-D and
      SDS, and positively correlated with the RSES, SSQ and PSS (all p < 0.05),
      although the correlation between the RS and CES-D was somewhat lower than that in
      previous studies. Factor analyses indicated a one-factor solution for RS-14, but
      as for RS, the result was not consistent with previous studies. CONCLUSIONS: This
      study demonstrates that the Japanese version of RS has psychometric properties
      with high degrees of internal consistency, high test-retest reliability, and
      relatively low concurrent validity. RS-14 was equivalent to the RS in internal
      consistency, test-retest reliability, and concurrent validity. Low scores on the
      RS, a positive correlation between the RS and perceived stress, and a relatively
      low correlation between the RS and depressive symptoms in this study suggest that
      validity of the Japanese version of the RS might be relatively low compared with
      the original English version.

PMID- 21083896
TI  - Extracorporeal life support in pediatric cardiac dysfunction.
AB  - BACKGROUND: Low cardiac output (LCO) after corrective surgery remains a serious
      complication in pediatric congenital heart diseases (CHD). In the case of
      refractory LCO, extra corporeal life support (ECLS) extra corporeal membrane
      oxygenation (ECMO) or ventricle assist devices (VAD) is the final therapeutic
      option. In the present study we have reviewed the outcomes of pediatric patients
      after corrective surgery necessitating ECLS and compared outcomes with pediatric
      patients necessitating ECLS because of dilatated cardiomyopathy (DCM). METHODS: A
      retrospective single-centre cohort study was evaluated in pediatric patients,
      between 1991 and 2008, that required ECLS. A total of 48 patients received ECLS,
      of which 23 were male and 25 female. The indications for ECLS included CHD in 32
      patients and DCM in 16 patients. RESULTS: The mean age was 1.2 +/- 3.9 years for
      CHD patients and 10.4 +/- 5.8 years for DCM patients. Twenty-six patients
      received ECMO and 22 patients received VAD. A total of 15 patients out of 48
      survived, 8 were discharged after myocardial recovery and 7 were discharged after
      successful heart transplantation. The overall mortality in patients with
      extracorporeal life support was 68%. CONCLUSION: Although the use of ECLS shows a
      significantly high mortality rate it remains the ultimate chance for children.
      For better results, ECLS should be initiated in the operating room or shortly
      thereafter. Bridge to heart transplantation should be considered if there is no
      improvement in cardiac function to avoid irreversible multiorgan failure (MFO).

PMID- 21083897
TI  - "First pain" in humans: convergent and specific forebrain responses.
AB  - BACKGROUND: Brief heat stimuli that excite nociceptors innervated by finely
      myelinated (Adelta) fibers evoke an initial, sharp, well-localized pain ("first
      pain") that is distinguishable from the delayed, less intense, more prolonged
      dull pain attributed to nociceptors innervated by unmyelinated (C) fibers
      ("second pain"). In the present study, we address the question of whether a
      brief, noxious heat stimulus that excites cutaneous Adelta fibers activates a
      distinct set of forebrain structures preferentially in addition to those with
      similar responses to converging input from C fibers. Heat stimuli at two
      temperatures were applied to the dorsum of the left hand of healthy volunteers in
      a functional brain imaging (fMRI) paradigm and responses analyzed in a set of
      volumes of interest (VOI). RESULTS: Brief 41 degrees C stimuli were painless and
      evoked only C fiber responses, but 51 degrees C stimuli were at pain threshold
      and preferentially evoked Adelta fiber responses. Most VOI responded to both
      intensities of stimulation. However, within volumes of interest, a contrast
      analysis and comparison of BOLD response latencies showed that the bilateral
      anterior insulae, the contralateral hippocampus, and the ipsilateral posterior
      insula were preferentially activated by painful heat stimulation that excited
      Adelta fibers. CONCLUSIONS: These findings show that two sets of forebrain
      structures mediate the initial sharp pain evoked by brief cutaneous heat
      stimulation: those responding preferentially to the brief stimulation of Adelta
      heat nociceptors and those with similar responses to converging inputs from the
      painless stimulation of C fibers. Our results suggest a unique and specific
      physiological basis, at the forebrain level, for the "first pain" sensation that
      has long been attributed to Adelta fiber stimulation and support the concept that
      both specific and convergent mechanisms act concurrently to mediate pain.

PMID- 21083899
TI  - Educational sessions in pharmacovigilance: What do the doctors think?
AB  - BACKGROUND: The aim of this study was to determine physicians' opinion regarding
      pharmacovigilance feedback sessions. A survey was conducted in a teaching
      hospital, and the physicians who attended the sessions were invited to
      participate by filling out a structured questionnaire. All sessions included a
      review of adverse drug reactions identified at the hospital and information on
      pharmacovigilance issues (news on warnings released by regulatory agencies or
      drug toxicity problems identified by recently published studies in medical
      journals). The survey questions were related to the interest, satisfaction, and
      belief in the utility of the sessions. A Likert scale (0-10 points) was used to
      assess physicians' opinions. FINDINGS: A total of 159 physicians attended the
      sessions and 115 (72.3%) participated in the survey. The mean (SD) age was 38.9
      (12.1) years, and 72 (62.6%) were men. The mean (SD) scores of interest,
      satisfaction with the information provided, and belief in the utility of these
      sessions were 7.52 (1.61), 7.58 (1.46), and 8.05 (1.38) respectively. Significant
      differences were observed among physicians according to medical category and
      speciality in terms of interest, satisfaction, and belief in the utility of those
      sessions. CONCLUSIONS: Educational activities for physicians, such as feedback
      sessions, can be integrated into the pharmacovigilance activities. Doctors who
      attend the sessions are interested in and satisfied with the information provided
      and consider the sessions to be useful. Additional studies on the development and
      effectiveness of educational activities in pharmacovigilance are necessary.

PMID- 21083898
TI  - Functionally relevant microsatellites in sugarcane unigenes.
AB  - BACKGROUND: Unigene sequences constitute a rich source of functionally relevant
      microsatellites. The present study was undertaken to mine the microsatellites in
      the available unigene sequences of sugarcane for understanding their constitution
      in the expressed genic component of its complex polyploid/aneuploid genome,
      assessing their functional significance in silico, determining the extent of
      allelic diversity at the microsatellite loci and for evaluating their utility in
      large-scale genotyping applications in sugarcane. RESULTS: The average frequency
      of perfect microsatellite was 1/10.9 kb, while it was 1/44.3 kb for the long and
      hypervariable class I repeats. GC-rich trinucleotides coding for alanine and the
      GA-rich dinucleotides were the most abundant microsatellite classes. Out of
      15,594 unigenes mined in the study, 767 contained microsatellite repeats and for
      672 of these putative functions were determined in silico. The microsatellite
      repeats were found in the functional domains of proteins encoded by 364 unigenes.
      Its significance was assessed by establishing the structure-function relationship
      for the beta-amylase and protein kinase encoding unigenes having repeats in the
      catalytic domains. A total of 726 allelic variants (7.42 alleles per locus) with
      different repeat lengths were captured precisely for a set of 47 fluorescent dye
      labeled primers in 36 sugarcane genotypes and five cereal species using the
      automated fragment analysis system, which suggested the utility of designed
      primers for rapid, large-scale and high-throughput genotyping applications in
      sugarcane. Pair-wise similarity ranging from 0.33 to 0.84 with an average of 0.40
      revealed a broad genetic base of the Indian varieties in respect of functionally
      relevant regions of the large and complex sugarcane genome. CONCLUSION:
      Microsatellite repeats were present in 4.92% of sugarcane unigenes, for most
      (87.6%) of which functions were determined in silico. High level of allelic
      diversity in repeats including those present in the functional domains of
      proteins encoded by the unigenes demonstrated their use in assay of useful
      variation in the genic component of complex polyploid sugarcane genome.

PMID- 21083900
TI  - Von willebrand factor increases endothelial cell adhesiveness for human
      mesenchymal stem cells by activating p38 mitogen-activated protein kinase.
AB  - INTRODUCTION: Delivered systemically or natively circulating mesenchymal stem
      cells accumulate in injured tissues. During homing mesenchymal stem cells adhere
      to endothelial cells and infiltrate underlying tissue. Previously we have shown
      that adhesiveness of endothelial cells for mesenchymal stem cells correlates with
      the inhibition of mitochondrial function of endothelial cells and secretion of
      von Willebrand factor. We hypothesized that von Willebrand factor is an
      auto/paracrine regulator of endothelial cell adhesiveness and studied the effect
      of von Willebrand factor on adhesion of mesenchymal stem cells to endothelial
      cells. METHODS: We used Affymetrix DNA microarrays, human protein phospho-MAPK
      array, Western blot, cell-based ELISA and flow cytometry analysis to study the
      activation of endothelial cells by von Willebrand factor. Cell adhesion assay and
      protein kinase inhibitors were used to evaluate the role of mitogen-activated
      protein kinases in the regulation of endothelial cell adhesiveness for
      mesenchymal stem cell. RESULTS: Treatment of endothelial cells with von
      Willebrand factor stimulated the mesenchymal stem cell adhesion in a time- and
      concentration-dependent manner. Mesenchymal stem cells did not adhere to
      immobilized von Willebrand factor and did not express receptors for von
      Willebrand factor suggesting that the stimulation of the mesenchymal stem cell
      adhesion is a result of endothelial cell activation with von Willebrand factor.
      Treatment of endothelial cells with von Willebrand factor activated ERK-1,2 and
      p38 MAPK without an effect on gene or cell surface expression of E-selectin, P
      selectin, VCAM1 and ICAM1. Inhibition of p38 MAPK, but not ERK-1,2, in
      endothelial cells completely abrogated the stimulation of the mesenchymal stem
      cell adhesion by von Willebrand factor. CONCLUSIONS: Von Willebrand factor is an
      auto/paracrine regulator of endothelial cells. Activation of p38 MAPK in
      endothelial cells by von Willebrand factor is responsible for the regulation of
      endothelial cell adhesiveness for mesenchymal stem cells.

PMID- 21083901
TI  - Lifetime health effects and medical costs of integrated stroke services - a non
      randomized controlled cluster-trial based life table approach.
AB  - BACKGROUND: Economic evaluation of stroke services indicates that such services
      may lead to improved quality of life at affordable cost. The present study
      assesses lifetime health impact and cost consequences of stroke in an integrated
      service setting. METHODS: The EDISSE study is a prospective non-randomized
      controlled cluster trial that compared stroke services (n = 151 patients) to
      usual care (n = 187 patients). Health status and cost trial-data were entered in
      multi-dimensional stroke life-tables. The tables distinguish four levels of
      disability which are defined by the modified Rankin scale. Quality-of-life scores
      (EuroQoL-5D), transition and survival probabilities are based on concurrent Dutch
      follow-up studies. Outcomes are quality-adjusted life years lived and lifetime
      medical cost by disability category. An economic analysis compares outcomes from
      a successful stroke service to usual care, by bootstrapping individual costs and
      effects data from patients in each arm. RESULTS: Lifetime costs and QALYs after
      stroke depend on age-of-onset of first-ever stroke. Lifetime QALYs after stroke
      are 2.42 (90% CI - 0.49 - 2.75) for male patients in usual care and 2.75 (-0.61;
      6.26) for females. Lifetime costs for men in the usual care setting are ?39,335
      (15,951; 79,837) and ?42,944 (14,081; 95,944) for women. A comparison with the
      stroke service results in an ICER of ?11,685 saved per QALY gained (?14,211 and
      ?7,745 for men and women respectively). This stroke service is with 90% certainty
      cost-effective. CONCLUSIONS: Our analysis shows the potential of large health
      benefits and cost savings of stroke services, taking a lifetime perspective, also
      in other European settings.

PMID- 21083902
TI  - Temporomandibular joint dysfunction and orthognathic surgery: a retrospective
      study.
AB  - BACKGROUND: Relations between maxillo-mandibular deformities and TMJ disorders
      have been the object of different studies in medical literature and there are
      various opinions concerning the alteration of TMJ dysfunction after orthognathic
      surgery. The purpose of the present study was to evaluate TMJ disorders changes
      before and after orthognathic surgery, and to assess the risk of creating new TMJ
      symptoms on asymptomatic patients. METHODS: A questionnaire was sent to 176
      patients operated at the Maxillo-Facial Service of the Lille's 2 Universitary
      Hospital Center (Chairman Pr Joel Ferri) from 01.01.2006 to 01.01.2008. 57
      patients (35 females and 22 males), age range from 16 to 65 years old, filled the
      questionnaire. The prevalence and the results on pain, sounds, clicking, joint
      locking, limited mouth opening, and tenseness were evaluated comparing different
      subgroups of patients. RESULTS: TMJ symptoms were significantly reduced after
      treatment for patients with pre-operative symptoms. The overall subjective
      treatment outcome was: improvement for 80.0% of patients, no change for 16.4% of
      patients, and an increase of symptoms for 3.6% of them. Thus, most patients were
      very satisfied with the results. However the appearance of new onset of TMJ
      symptoms is common. There was no statistical difference in the prevalence of
      preoperative TMJ symptoms and on postoperative results in class II compared to
      class III patients. CONCLUSIONS: These observations demonstrate that: there is a
      high prevalence of TMJ disorders in dysgnathic patients; most of patients with
      preoperative TMJ signs and symptoms can improve TMJ dysfunction and pain levels
      can be reduced by orthognathic treatment; a percentage of dysgnathic patients who
      were preoperatively asymptomatic can develop TMJ disorders after surgery but this
      risk is low.

PMID- 21083903
TI  - Suicide and unintentional poisoning mortality trends in the United States, 1987
      2006: two unrelated phenomena?
AB  - BACKGROUND: Two counter trends in injury mortality have been separately reported
      in the US in recent times - a declining suicide rate and a rapidly rising
      unintentional poisoning mortality rate. Poisoning suicides are especially
      difficult to detect, and injury of undetermined intent is the underlying cause-of
      death category most likely to reflect this difficulty. We compare suicide and
      poisoning mortality trends over two decades in a preliminary assessment of their
      independence and implications for suicide misclassification. METHODS: Description
      of overall and gender- and age-specific trends using national mortality data from
      WISQARS, the Web-based Injury Statistics Query and Reporting System, maintained
      by the Centers for Disease Control and Prevention (CDC). Subjects were the
      936,633 residents dying in the 50 states and the District of Columbia between
      1987 and 2006 whose underlying cause of death was classified as suicide,
      unintentional poisoning, or injury mortality of undetermined intent. RESULTS: The
      official US suicide rate declined 18% between 1987 and 2000, from 12.71 to 10.43
      deaths per 100,000 population. It then increased to 11.15 deaths per 100,000 by
      2006, a 7% rise. By contrast to these much smaller rate changes for suicide, the
      unintentional poisoning mortality rate rose more than fourfold between 1987 and
      2006, from 2.19 to 9.22 deaths per 100,000. Only the population aged 65 years and
      older showed a sustained decline in the suicide rate over the entire observation
      period. Consistently highest in gender-age comparisons, the elderly male rate
      declined by 35%. The elderly female rate declined by 43%. Unlike rate trends for
      the non-elderly, both declines appeared independent of corresponding mortality
      trends for unintentional poisoning and poisoning of undetermined intent. The
      elderly also deviated from younger counterparts by having a smaller proportion of
      their injury deaths of undetermined intent classified as poisoning. Poisoning
      manifested as a less common method of suicide for this group than other
      decedents, except for those aged 15-24 years. Although remaining low, the
      undetermined poisoning mortality rate increased over the observation period.
      CONCLUSIONS: The official decline in the suicide rate between 1987 and 2000 may
      have been a partial artifact of misclassification of non-elderly suicides within
      unintentional poisoning mortality. We recommend in-depth national, regional, and
      local population-based research investigations of the poisoning-suicide nexus,
      and endorse calls for widening the scope of the definition of suicide and
      evaluation of its risk factors.

PMID- 21083904
TI  - The first three years of screening for medium chain acyl-CoA dehydrogenase
      deficiency (MCADD) by newborn screening ontario.
AB  - BACKGROUND: Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder
      of mitochondrial fatty acid oxidation and is one of the most common inborn errors
      of metabolism. Identification of MCADD via newborn screening permits the
      introduction of interventions that can significantly reduce associated morbidity
      and mortality. This study reports on the first three years of newborn screening
      for MCADD in Ontario, Canada. METHODS: Newborn Screening Ontario began screening
      for MCADD in April 2006, by quantification of acylcarnitines (primarily
      octanoylcarnitine, C8) in dried blood spots using tandem mass spectrometry.
      Babies with positive screening results were referred to physicians at one of five
      regional Newborn Screening Treatment Centres, who were responsible for diagnostic
      evaluation and follow-up care. RESULTS: From April 2006 through March 2009,
      approximately 439 000 infants were screened for MCADD in Ontario. Seventy-four
      infants screened positive, with a median C8 level of 0.68 uM (range 0.33-30.41
      uM). Thirty-one of the screen positive infants have been confirmed to have MCADD,
      while 36 have been confirmed to be unaffected. Screening C8 levels were higher
      among infants with MCADD (median 8.93 uM) compared to those with false positive
      results (median 0.47 uM). Molecular testing was available for 29 confirmed cases
      of MCADD, 15 of whom were homozygous for the common c.985A > G mutation. Infants
      homozygous for the common mutation tended to have higher C8 levels (median 12.13
      uM) relative to compound heterozygotes for c.985A > G and a second detectable
      mutation (median 2.01 uM). Eight confirmed mutation carriers were identified
      among infants in the false positive group. The positive predictive value of a
      screen positive for MCADD was 46%. The estimated birth prevalence of MCADD in
      Ontario is approximately 1 in 14 000. CONCLUSIONS: The birth prevalence of MCADD
      and positive predictive value of the screening test were similar to those
      identified by other newborn screening programs internationally. We observed some
      evidence of correlation between genotype and biochemical phenotype (C8 levels),
      and between C8 screening levels and eventual diagnosis. Current research
      priorities include further examining the relationships among genotype,
      biochemical phenotype, and clinical phenotype, with the ultimate goal of
      improving clinical risk prediction in order to provide tailored disease
      management advice and genetic counselling to families.

PMID- 21083905
TI  - The influence of persistent pathogens on circulating levels of inflammatory
      markers: a cross-sectional analysis from the Multi-Ethnic Study of
      Atherosclerosis.
AB  - BACKGROUND: Systemic inflammation is linked to cardiovascular risk, but the
      influence of persistent pathogens, which are conventionally dichotomously
      categorized, on circulating levels of inflammatory markers is not clear. Antibody
      levels of pathogens have not been examined in relation to inflammation. METHODS:
      Using data from a subsample of the Multi-Ethnic Study of Atherosclerosis, we
      examined circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP) and
      fibrinogen in relation to five common persistent pathogens: cytomegalovirus,
      herpes simplex virus-1, Hepatitis A virus, Helicobacter pylori and Chlamydia
      pneumoniae. We tested the hypothesis that the number of seropositive pathogens
      (based on conventional cut-off points) would not be as sensitive a marker of
      inflammation as immune response measured by antibody levels to pathogens.
      RESULTS: High antibody response to multiple pathogens showed graded and
      significant associations with IL-6 (p < 0.001), CRP (p = 0.04) and fibrinogen (p
      = 0.001), whereas seropositive pathogen burden did not. In multiple linear
      regression models, high antibody response to multiple pathogens maintained a
      positive association only with IL-6 (4.4% per pathogen exhibiting high antibody
      response, 95% CI 0.0-8.9). CONCLUSIONS: High antibody response to pathogens was a
      more consistent marker of inflammatory outcomes compared to seropositivity alone
      and high antibody response to multiple pathogens was a stronger marker compared
      to any single pathogen.

PMID- 21083906
TI  - Prevalence and analysis of Pseudomonas aeruginosa in chinchillas.
AB  - BACKGROUND: Chinchillas (Chinchilla laniger) are popular as pets and are often
      used as laboratory animals for various studies. Pseudomonas aeruginosa is a major
      infectious agent that causes otitis media, pneumonia, septicaemia enteritis, and
      sudden death in chinchillas. This bacterium is also a leading cause of nosocomial
      infections in humans. To prevent propagation of P. aeruginosa infection among
      humans and animals, detailed characteristics of the isolates, including
      antibiotic susceptibility and genetic features, are needed. In this study, we
      surveyed P. aeruginosa distribution in chinchillas bred as pets or laboratory
      animals. We also characterized the isolates from these chinchillas by testing for
      antibiotic susceptibility and by gene analysis. RESULTS: P. aeruginosa was
      isolated from 41.8% of the 67 chinchillas included in the study. Slide
      agglutination and pulsed-field gel electrophoresis discriminated 5 serotypes and
      7 unique patterns, respectively. For the antibiotic susceptibility test, 40.9% of
      isolates were susceptible to gentamicin, 77.3% to ciprofloxacin, 77.3% to
      imipenem, and 72.7% to ceftazidime. DNA analyses confirmed that none of the
      isolates contained the gene encoding extended-spectrum beta-lactamases; however,
      2 of the total 23 isolates were found to have a gene similar to the pilL gene
      that has been identified in the pathogenicity island of a clinical isolate of P.
      aeruginosa. CONCLUSIONS: P. aeruginosa is widely spread in chinchillas, including
      strains with reduced susceptibility to the antibiotics and highly virulent
      strains. The periodic monitoring should be performed to help prevent the
      propagation of this pathogen and reduce the risk of infection from chinchillas to
      humans.

PMID- 21083907
TI  - Exclusive and adjuvant radiotherapy in breast cancer patients with synchronous
      metastases.
AB  - BACKGROUND: Data from the Surveillance, Epidemiology, and End Results program and
      the European Concerted Action on survival and Care of Cancer Patients (EUROCARE)
      project indicate that about 6% of women newly diagnosed with breast cancer have
      stage IV disease, representing about 12 600 new cases per year in the United
      States in 2005. Historically, local therapy of the primary tumor in this setting
      has been aimed solely at symptom palliation. However, several studies suggest
      that surgical excision of the primary tumor can prolong these patients' survival.
      DISCUSSION: Exclusive locoregional radiotherapy is an alternative form of
      locoregional treatment in this setting and may represent an effective alternative
      to surgery in this setting. Here we discuss current issues regarding exclusive
      and adjuvant locoregional radiotherapy in breast cancer patients with synchronous
      metastases. SUMMARY: Several studies suggest that surgery or exclusive
      irradiation of the primary tumor is associated with better survival in breast
      cancer patients with synchronous metastases and that exclusive locoregional
      radiotherapy may represent an effective alternative to surgery in this setting.
      Results of well-designed prospective studies are needed to re-evaluate treatment
      of the primary breast tumor in patients with metastases at diagnosis, and to
      identify those patients who are most likely to benefit.

PMID- 21083908
TI  - Determinants of preventable readmissions in the United States: a systematic
      review.
AB  - BACKGROUND: Hospital readmissions are a leading topic of healthcare policy and
      practice reform because they are common, costly, and potentially avoidable
      events. Hospitals face the prospect of reduced or eliminated reimbursement for an
      increasing number of preventable readmissions under nationwide cost savings and
      quality improvement efforts. To meet the current changes and future expectations,
      organizations are looking for potential strategies to reduce readmissions. We
      undertook a systematic review of the literature to determine what factors are
      associated with preventable readmissions. METHODS: We conducted a review of the
      English language medicine, health, and health services research literature (2000
      to 2009) for research studies dealing with unplanned, avoidable, preventable, or
      early readmissions. Each of these modifying terms was included in keyword
      searches of readmissions or rehospitalizations in Medline, ISI, CINAHL, The
      Cochrane Library, ProQuest Health Management, and PAIS International. Results
      were limited to US adult populations. RESULTS: The review included 37 studies
      with significant variation in index conditions, readmitting conditions,
      timeframe, and terminology. Studies of cardiovascular-related readmissions were
      most common, followed by all cause readmissions, other surgical procedures, and
      other specific-conditions. Patient-level indicators of general ill health or
      complexity were the commonly identified risk factors. While more than one study
      demonstrated preventable readmissions vary by hospital, identification of many
      specific organizational level characteristics was lacking. CONCLUSIONS: The
      current literature on preventable readmissions in the US contains evidence from a
      variety of patient populations, geographical locations, healthcare settings,
      study designs, clinical and theoretical perspectives, and conditions. However,
      definitional variations, clear gaps, and methodological challenges limit
      translation of this literature into guidance for the operation and management of
      healthcare organizations. We recommend that those organizations that propose to
      reward reductions in preventable readmissions invest in additional research
      across multiple hospitals in order to fill this serious gap in knowledge of great
      potential value to payers, providers, and patients.

PMID- 21083910
TI  - Nitrogen dioxide concentrations in neighborhoods adjacent to a commercial
      airport: a land use regression modeling study.
AB  - BACKGROUND: There is growing concern in communities surrounding airports
      regarding the contribution of various emission sources (such as aircraft and
      ground support equipment) to nearby ambient concentrations. We used extensive
      monitoring of nitrogen dioxide (NO2) in neighborhoods surrounding T.F. Green
      Airport in Warwick, RI, and land-use regression (LUR) modeling techniques to
      determine the impact of proximity to the airport and local traffic on these
      concentrations. METHODS: Palmes diffusion tube samplers were deployed along the
      airport's fence line and within surrounding neighborhoods for one to two weeks.
      In total, 644 measurements were collected over three sampling campaigns (October
      2007, March 2008 and June 2008) and each sampling location was geocoded. GIS
      based variables were created as proxies for local traffic and airport activity. A
      forward stepwise regression methodology was employed to create general linear
      models (GLMs) of NO2 variability near the airport. The effect of local
      meteorology on associations with GIS-based variables was also explored. RESULTS:
      Higher concentrations of NO2 were seen near the airport terminal, entrance roads
      to the terminal, and near major roads, with qualitatively consistent spatial
      patterns between seasons. In our final multivariate model (R2 = 0.32), the local
      influences of highways and arterial/collector roads were statistically
      significant, as were local traffic density and distance to the airport terminal
      (all p < 0.001). Local meteorology did not significantly affect associations with
      principal GIS variables, and the regression model structure was robust to various
      model-building approaches. CONCLUSION: Our study has shown that there are clear
      local variations in NO2 in the neighborhoods that surround an urban airport,
      which are spatially consistent across seasons. LUR modeling demonstrated a strong
      influence of local traffic, except the smallest roads that predominate in
      residential areas, as well as proximity to the airport terminal.

PMID- 21083909
TI  - Robust patterns in the stochastic organization of filopodia.
AB  - BACKGROUND: Filopodia are actin-based cellular projections that have a critical
      role in initiating and sustaining directional migration in vertebrate cells.
      Filopodia are highly dynamic structures that show a rich diversity in appearance
      and behavior. While there are several mathematical models of filopodia initiation
      and growth, testing the capacity of these theoretical models in predicting
      empirical behavior has been hampered by a surprising shortage of quantitative
      data related to filopodia. Neither is it clear how quantitatively robust the
      cellular filopodial network is and how perturbations alter it. RESULTS: We have
      measured the length and interfilopodial separation distances of several thousand
      filopodia in the rodent cell line Rat2 and measured these parameters in response
      to genetic, chemical and physical perturbation. Our work shows that length and
      separation distance have a lognormal pattern distribution over their entire
      detection range (0.4 MUm to 50 MUm). CONCLUSIONS: We find that the lognormal
      distribution of length and separation is robust and highly resistant to
      perturbation. We also find that length and separation are independent variables.
      Most importantly, our empirical data is not entirely in agreement with
      predictions made based on existing theoretical models and that filopodial size
      and separation are an order of magnitude larger than what existing models
      suggest.

PMID- 21083911
TI  - Could chiropractors screen for adverse drug events in the community? Survey of US
      chiropractors.
AB  - BACKGROUND: The "Put Prevention into Practice" campaign of the US Public Health
      Service (USPHS) was launched with the dissemination of the Clinician's Handbook
      of Preventive Services that recommended standards of clinical care for various
      prevention activities, including preventive clinical strategies to reduce the
      risk of adverse drug events. We explored whether nonprescribing clinicians such
      as chiropractors may contribute to advancing drug safety initiatives by
      identifying potential adverse drug events in their chiropractic patients, and by
      bringing suspected adverse drug events to the attention of the prescribing
      clinicians. METHODS: Mail survey of US chiropractors about their detection of
      potential adverse drug events in their chiropractic patients. RESULTS: Over half
      of responding chiropractors (62%) reported having identified a suspected adverse
      drug event occurring in one of their chiropractic patients. The severity of
      suspected drug-related events detected ranged from mild to severe. CONCLUSIONS:
      Chiropractors or other nonprescribing clinicians may be in a position to detect
      potential adverse drug events in the community. These detection and reporting
      mechanisms should be standardized and policies related to clinical case
      management of suspected adverse drug events occurring in their patients should be
      developed.

PMID- 21083912
TI  - Health promoting settings in primary health care - "halsotorg": an implementation
      analysis.
AB  - BACKGROUND: Sweden, like many other western countries, faces increasing rates of
      lifestyle related diseases and corresponding rise in costs for health care. To
      meet these challenges, a number of efforts have been introduced at different
      societal levels. One such effort is "Halsotorg" (HS). HS is a new health
      promotion setting that emerged in collaboration between the Swedish County
      Councils and Apoteket AB, a state-owned pharmacy company. HS's overall aim was to
      improve population health and facilitate inhabitants' responsibility for self
      care. A new National Public Health Policy, introduced in 2008, emphasizes more
      focus on individual's needs and responsibility as well as strong need for county
      councils to provide supportive environment for individual-centred health services
      and increased health literacy among the population. In light of this policy,
      there is a need to examine existing settings that can provide supportive
      environment for individuals at community level. The aim of this study was to
      explore HS's policy implementation at local level and analyse HS's activities, in
      order to provide a deeper understanding of HS's potential as a health promoting
      setting. METHODS: Materials included a survey and key documents related to the
      development and nature of HS on local and national levels. A policy analysis
      inspired by Walt and Gilson was used in data analysis. In addition, an analysis
      using the principles of health promotion in relation to HS policy process and
      activities was also carried out. RESULTS: The analysis illuminated strengths and
      weaknesses in the policy process, its actors, contextual factors and activities.
      The health communication approach in the analysed documents contained health
      promoting intentions but the health promoting approach corresponding to a health
      promoting setting was neither apparent nor shared among the stakeholders. This
      influenced the interpretation and implementation of HS negatively. CONCLUSIONS:
      The analysis indicates that HS has potential to be a valuable health promotion
      setting for both population and individuals, given the strong intentions for a
      health and empowerment building approach that is expressed in the documents.
      However, for a more sustainable implementation of HS, there is need for an in-
      depth understanding of the health promotion approach among HS stakeholders.

PMID- 21083913
TI  - The relevance of traditional knowledge systems for ethnopharmacological research:
      theoretical and methodological contributions.
AB  - BACKGROUND: Ethnopharmacology is at the intersection of the medical, natural, and
      social sciences. Despite its interdisciplinary nature, most ethnopharmacological
      research has been based on the combination of the chemical, biological, and
      pharmacological sciences. Far less attention has been given to the social
      sciences, including anthropology and the study of traditional knowledge systems.
      METHODS: I reviewed the literature on traditional knowledge systems highlighting
      its potential theoretical and methodological contributions to ethnopharmacology.
      RESULTS: I discuss three potential theoretical contributions of traditional
      knowledge systems to ethnopharmacological research. First, while many plants used
      in indigenous pharmacopoeias have active compounds, those compounds do not always
      act alone in indigenous healing systems. Research highlights the holistic nature
      of traditional knowledge systems and helps understand plant's efficacy in its
      cultural context. Second, research on traditional knowledge systems can improve
      our understanding of how ethnopharmacological knowledge is distributed in a
      society, and who benefits from it. Third, research on traditional knowledge
      systems can enhance the study of the social relations that enable the generation,
      maintenance, spread, and devolution of cultural traits and innovations, including
      ethnopharmacological knowledge. At a methodological level, some
      ethnopharmacologists have used anthropological tools to understand the context of
      plant use and local meanings of health and disease. I discuss two more potential
      methodological contributions of research on traditional knowledge systems to
      ethnopharmacological research. First, traditional knowledge systems research has
      developed methods that would help ethnopharmacologists understand how people
      classify illnesses and remedies, a fundamental aspect of folk medicinal plant
      selection criteria. Second, ethnopharmacologists could also borrow methods
      derived from cultural consensus theory to have a broader look at intracultural
      variation and at the analysis of transmission and loss of traditional
      ethnopharmacological knowledge. CONCLUSIONS: Ethical considerations in the
      ethnopharmacology of the 21st century should go beyond the recognition of the
      Intellectual Property Rights or the acquisition of research permits, to include
      considerations on the healthcare of the original holders of ethnopharmacological
      knowledge. Ethnopharmacology can do more than speed up to recover the traditional
      knowledge of indigenous peoples to make it available for the development of new
      drugs. Ethnopharmacologists can work with health care providers in the developing
      world for the local implementation of ethnopharmacological research results.

PMID- 21083914
TI  - A novel genetically-obese rat model with elevated 11 beta-hydroxysteroid
      dehydrogenase type 1 activity in subcutaneous adipose tissue.
AB  - 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) catalyzes the
      conversion of inactive glucocorticoids to active glucocorticoids and plays an
      important role in the development of obesity and metabolic syndrome. 11 beta-HSD1
      activity is lower in liver and higher in omental adipose tissue of obese rodent
      models like obese zucker rats, Ob/Ob and db/db mice. Here, we report the 11 beta
      HSD1 activity in liver and adipose tissue of lean and obese rats of WNIN/Ob
      strain, a new genetic rat model of obesity. 11 beta-HSD1 activity in liver,
      omental and subcutaneous adipose tissues of 3 month-old male WNIN/Ob lean and
      obese rats was assayed. As observed in other rodent models, 11 beta-HSD1 activity
      was lower in liver and higher in omental adipose tissue. In contrast to other
      rodent obese models, WNIN/Ob obese rats had elevated 11 beta-HSD1 activity in
      subcutaneous adipose tissue, which is in line with the observation in human
      obesity. Here, we conclude that dysregulation of 11 beta-HSD1 in WNIN/Ob obese
      rat model is identical to human obesity, which makes it an excellent model for
      studying the effect of 11 beta-HSD1 inhibitors in ameliorating obesity and
      metabolic syndrome.

PMID- 21083915
TI  - Successfully resisting a pathogen is rarely costly in Daphnia magna.
AB  - BACKGROUND: A central hypothesis in the evolutionary ecology of parasitism is
      that trade-offs exist between resistance to parasites and other fitness
      components such as fecundity, growth, survival, and predator avoidance, or
      resistance to other parasites. These trade-offs are called costs of resistance.
      These costs fall into two broad categories: constitutive costs of resistance,
      which arise from a negative genetic covariance between immunity and other fitness
      related traits, and inducible costs of resistance, which are the physiological
      costs incurred by hosts when mounting an immune response. We sought to study
      inducible costs in depth using the crustacean Daphnia magna and its bacterial
      parasite Pasteuria ramosa. RESULTS: We designed specific experiments to study the
      costs induced by exposure to this parasite, and we re-analysed previously
      published data in an effort to determine the generality of such costs. However,
      despite the variety of genetic backgrounds of both hosts and parasites, and the
      different exposure protocols and environmental conditions used in these
      experiment, this work showed that costs of exposure can only rarely be detected
      in the D. magna-P. ramosa system. CONCLUSIONS: We discuss possible reasons for
      this lack of detectable costs, including scenarios where costs of resistance to
      parasites might not play a major role in the co-evolution of hosts and parasites.

PMID- 21083916
TI  - Myotoxicity of telbivudine in pre-existing muscle damage.
AB  - OBJECTIVES: It is unknown if telbivudine causes muscle damage only in patients
      with pre-existing muscle pathology. CASE REPORT: A 27 yo male of African origin
      received telbivudine for hepatitis B during 3 months. Three weeks after
      initiation of the drug he developed myalgia, and tiredness. Creatine-kinase
      increased from 278 U/l (n, <170 U/l) at baseline to 3243 U/l. Shortly after
      discontinuation of telbivudine muscle symptoms and hyper-CK-emia disappeared. The
      findings suggest that pre-existing muscle damage favored the myotoxic effect of
      telbivudine. CONCLUSIONS: Telbivudine appears to cause accelerated muscle
      toxicity if given to patients who already have muscle damage. Patients under
      telbivudine should be closely monitored for muscular side effects and those with
      pre-existing muscle damage should not receive the drug.

PMID- 21083917
TI  - High-level production of animal-free recombinant transferrin from Saccharomyces
      cerevisiae.
AB  - BACKGROUND: Animal-free recombinant proteins provide a safe and effective
      alternative to tissue or serum-derived products for both therapeutic and
      biomanufacturing applications. While recombinant insulin and albumin already
      exist to replace their human counterparts in cell culture media, until recently
      there has been no equivalent for serum transferrin. RESULTS: The first microbial
      system for the high-level secretion of a recombinant transferrin (rTf) has been
      developed from Saccharomyces cerevisiae strains originally engineered for the
      commercial production of recombinant human albumin (Novozymes' Recombumin(r) USP
      NF) and albumin fusion proteins (Novozymes' albufuse(r)). A full-length non-N
      linked glycosylated rTf was secreted at levels around ten-fold higher than from
      commonly used laboratory strains. Modification of the yeast 2 MUm-based
      expression vector to allow overexpression of the ER chaperone, protein disulphide
      isomerase, further increased the secretion of rTf approximately twelve-fold in
      high cell density fermentation. The rTf produced was functionally equivalent to
      plasma-derived transferrin. CONCLUSIONS: A Saccharomyces cerevisiae expression
      system has enabled the cGMP manufacture of an animal-free rTf for industrial cell
      culture application without the risk of prion and viral contamination, and
      provides a high-quality platform for the development of transferrin-based
      therapeutics.

PMID- 21083918
TI  - A bio-psycho-social exercise program (RUCKGEWINN) for chronic low back pain in
      rehabilitation aftercare--study protocol for a randomised controlled trial.
AB  - BACKGROUND: There is strong, internationally confirmed evidence for the short
      term effectiveness of multimodal interdisciplinary specific treatment programs
      for chronic back pain. However, the verification of long-term sustainability of
      achieved effects is missing so far. For long-term improvement of pain and
      functional ability high intervention intensity or high volume seems to be
      necessary (> 100 therapy hours). Especially in chronic back pain rehabilitation,
      purposefully refined aftercare treatments offer the possibility to intensify
      positive effects or to increase their sustainability. However, quality assured
      goal-conscious specific aftercare programs for the rehabilitation of chronic back
      pain are absent. METHODS/DESIGN: This study aims to examine the efficacy of a
      specially developed bio-psycho-social chronic back pain specific aftercare
      intervention (RUCKGEWINN) in comparison to the current usual aftercare (IRENA)
      and a control group that is given an educational booklet addressing pain
      conditioned functional ability and back pain episodes. Overall rehabilitation
      effects as well as predictors for compliance to the aftercare programs are
      analysed. Therefore, a multicenter prospective 3-armed randomised controlled
      trial is conducted. 456 participants will be consecutively enrolled in inpatient
      and outpatient rehabilitation and assigned to either one of the three study arms.
      Outcomes are measured before and after rehabilitation. Aftercare programs are
      assessed at ten month follow up after dismissal form rehabilitation. DISCUSSION:
      Special methodological and logistic challenges are to be mastered in this trial,
      which accrue from the interconnection of aftercare interventions to their
      residential district and the fact that the proportion of patients who take part
      in aftercare programs is low. The usability of the aftercare program is based on
      the transference into the routine care and is also reinforced by developed
      manuals with structured contents, media and material for organisation assistance
      as well as training manuals for therapists in the aftercare.

PMID- 21083919
TI  - Rectal laterally spreading tumors successfully treated in two steps by endoscopic
      submucosal dissection and endoscopic mucosal resection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is an advanced technique of
      therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for
      superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct
      dissection of the submucosa and large lesions can be resected en bloc. ESD is not
      limited by resection size, increases histologically complete resection rates and
      may reduce the local recurrence. Nevertheless, the technique is time-consuming,
      technically demanding and associated with a high complication rate. To reduce the
      risk of complications, different devices and technical advances have been
      proposed with conflicting results and, still, ESD en bloc resections of huge
      lesions are associated with increased complications. CASE PRESENTATION: We
      successfully used a combined ESD/EMR technique for huge rectal laterally
      spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the
      lesion followed by piecemeal resection (2-3 pieces) of the central part of the
      tumour. In all three patients we obtained the complete dissection of the polyp
      and the complete histological evaluation in absence of complications and
      recurrence at 6 months' follow up. CONCLUSIONS: In the treatment of rectal LSTs,
      the combined treatment - ESD/EMR resection may be considered a suitable
      therapeutic option, indicated in selected cases as an alternative to surgery, in
      which the two techniques are neither reliable nor safe separately. However, to
      confirm our results, larger trials with longer follow up are required together
      with improvement of the technique and of the technical devices.

PMID- 21083920
TI  - Metabolic abnormalities in adolescents with polycystic ovary syndrome in south
      China.
AB  - BACKGROUND: Adults with polycystic ovary syndrome (PCOS) can have multiple
      metabolic abnormalities. However, studies in the adolescent population are still
      limited and these results seem to vary widely. This study was to investigate the
      metabolic abnormalities in adolescents with PCOS in South China and the potential
      risk factors contributed to these health risks. METHODS: Anthropometric
      measurements and biochemical parameters were evaluated in 128 adolescents with
      PCOS and their age- and BMI-matched controls. RESULTS: The prevalence of pre
      diabetes, insulin resistance, hyperinsulinemia, dyslipidemia and metabolic
      syndrome in adolescents with PCOS was 11.7%, 46.9%, 29.7%, 22.7% and 4.7%,
      respectively. 16.3%, 74.4%, 67.4%, 39.5% and 14% of the PCOS subjects with BMI >
      85th had pre-diabetes, insulin resistance, hyperinsulinemia, dyslipidemia and
      metabolic syndrome, whereas 9.4%, 32.9%, 10.6%, 14.1% and 0% of the PCOS subjects
      with BMI < 85th had such disturbances. CONCLUSIONS: Adolescents with PCOS in
      South China had more metabolic abnormalities than their age- and BMI-matched non
      PCOS counterparts. Obesity could worsen insulin resistance, hyperinsulinemia and
      metabolic syndrome in PCOS adolescents.

PMID- 21083921
TI  - Does left atrial volume affect exercise capacity of heart transplant recipients?
AB  - BACKGROUND: Heart transplant (HT) recipients demonstrate limited exercise
      capacity compared to normal patients, very likely for multiple reasons. In this
      study we hypothesized that left atrial volume (LAV), which is known to predict
      exercise capacity in patients with various cardiac pathologies including heart
      failure and hypertrophic cardiomyopathy is associated with limited exercise
      capacity of HT recipients. METHODS: We analyzed 50 patients [age 57 +/-2 (SEM),
      12 females] who had a post-HT echocardiography and cardiopulmonary exercise test
      (CPX) within 9 weeks time at clinic follow up. The change in LAV (DeltaLAV) was
      also computed as the difference in LAV from the preceding one-year to the study
      echocardiogram. Correlations among the measured parameters were assessed with a
      Pearson's correlation analysis. RESULTS: LAV (n = 50) and DeltaLAV (n = 40)
      indexed to body surface area were 40.6 +/- 11.5 ml.m-2 and 1.9 +/- 8.5 ml.m
      2.year-1, data are mean +/- SD, respectively. Indexed LAV and DeltaLAV were both
      significantly correlated with the ventilatory efficiency, assessed by the VE/VCO2
      slope (r = 0.300, p = 0.038; r = 0.484, p = 0.002, respectively). LAV showed a
      significant correlation with peak oxygen consumption (r = -0.328, p = 0.020).
      CONCLUSIONS: Although our study is limited by a retrospective study design and
      relatively small number of patients, our findings suggest that enlarged LAV and
      increasing change in LAV is associated with the diminished exercise capacity in
      HT recipients and warrants further investigation to better elucidate this
      relationship.

PMID- 21083922
TI  - Effects of prescription adaptation by pharmacists.
AB  - BACKGROUND: Granting dispensing pharmacists the authority to prescribe has
      significant implications for pharmaceutical and health human resources policy,
      and quality of care. Despite the growing number of jurisdictions that have given
      pharmacists such privileges, there are few rigorous evaluations of these policy
      changes. This study will examine a January 2009 policy change in British Columbia
      (BC), Canada that allowed pharmacists to independently adapt and renew
      prescriptions. We hypothesize this policy increased drug utilization and drug
      costs, increased patient adherence to medication, and reduced total healthcare
      resource use. METHODS/DESIGN: We will study a population-based cohort of
      approximately 4 million BC residents from 2004 through 2010. We will use data
      from BC PharmaNet on all of the prescriptions obtained by this cohort during the
      study period, and link it to administrative billings from physicians and hospital
      discharges. Using interrupted time series analysis, we will study longitudinal
      changes in drug utilization and costs, medication adherence, and short-term
      health care use. Further, using hierarchical modelling, we will examine the
      factors at the regional, pharmacy, patient, and prescription levels that are
      associated with prescription adaptations and renewals. DISCUSSION: In a recent
      survey of Canadian policymakers, many respondents ranked the issue of prescribing
      privileges as one of their most pressing policy questions. No matter the results
      of our study, they will be important for policymakers, as our data will make
      policy decisions surrounding pharmacist prescribing more evidence-based.

PMID- 21083923
TI  - Modeling the clonal heterogeneity of stem cells.
AB  - Recent experimental studies suggest that tissue stem cell pools are composed of
      functionally diverse clones. Metapopulation models in ecology concentrate on
      collections of populations and their role in stabilizing coexistence and
      maintaining selected genetic or epigenetic variation. Such models are
      characterized by expansion and extinction of spatially distributed populations.
      We develop a mathematical framework derived from the multispecies metapopulation
      model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell
      metapopulations. In addition to normal stem cells, the model can be applied to
      cancer cell populations and their response to treatment. In our model
      disturbances may lead to expansion or contraction of cells with distinct
      properties, reflecting proliferation, apoptosis, and clonal competition. We first
      present closed-form expressions for the basic model which defines clonal dynamics
      in the presence of exogenous global disturbances. We then extend the model to
      include disturbances which are periodic and which may affect clones differently.
      Within the model framework, we propose a method to devise an optimal strategy of
      treatments to regulate expansion, contraction, or mutual maintenance of cells
      with specific properties.

PMID- 21083924
TI  - Skin prick testing does not reflect the presence of IgE against food allergens in
      adult eosinophilic esophagitis patients: a case study.
AB  - Skin prick testing is widely used to predict the presence of allergen-specific
      IgE. In eosinophilic esophagitis patients, who frequently exhibit
      polysensitization and broad reactivity upon skin prick testing, this is commonly
      used to aid avoidance recommendations in the clinical management of their
      disease. We present here the predictive value of skin prick testing for the
      presence of allergen-specific IgE, in 12 patients, determined by immunoblot
      against the allergen extracts using individual-matched serum. Our results
      demonstrate a high degree of predictive value for aeroallergens but a poor
      predictive value for food allergens. This suggests that skin prick testing likely
      identifies IgE reactivity towards aeroallergens in adult eosinophilic esophagitis
      but this is not true for foods. Consequently, IgE immunoblotting might be
      required for determining food avoidance in these patients.

PMID- 21083925
TI  - Radiosurgery for pituitary adenomas: evaluation of its efficacy and safety.
AB  - OBJECT: To assess the effects of radiosurgery (RS) on the radiological and
      hormonal control and its toxicity in the treatment of pituitary adenomas.
      METHODS: Retrospective analysis of 42 patients out of the first 48 consecutive
      patients with pituitary adenomas treated with RS between 1999 and 2008 with a 6
      months minimum follow-up. RS was delivered with Gamma Knife as a primary or
      adjuvant treatment. There were 14 patients with non-secretory adenomas and, among
      functioning adenomas, 9 were prolactinomas, 9 were adrenocorticotropic hormone
      secreting and 10 were growth hormone-secreting tumors. Hormonal control was
      defined as hormonal response (decline of more than 50% from the pre-RS levels)
      and hormonal normalization. Radiological control was defined as stasis or
      shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity
      outcomes. Hypopituitarism was defined as the initiation of any hormone
      replacement therapy and visual deficit as loss of visual acuity or visual field
      after RS. RESULTS: The median follow-up was 42 months (6-109 months). The median
      dose was 12,5 Gy (9 - 15 Gy) and 20 Gy (12 - 28 Gy) for non-secretory and
      secretory adenomas, respectively. Tumor growth was controlled in 98% (41 in 42)
      of the cases and tumor shrinkage occurred in 10% (4 in 42) of the cases. The 3
      year actuarial rate of hormonal control and normalization were 62,4% and 37,6%,
      respectively, and the 5-year actuarial rate were 81,2% and 55,4%, respectively.
      The median latency period for hormonal control and normalization was,
      respectively, 15 and 18 months. On univariate analysis, there were no
      relationships between median dose or tumoral volume and hormonal control or
      normalization. There were no patients with visual deficit and 1 patient had
      hypopituitarism after RS. CONCLUSIONS: RS is an effective and safe therapeutic
      option in the management of selected patients with pituitary adenomas. The short
      latency of the radiation response, the highly acceptable radiological and
      hormonal control and absence of complications at this early follow-up are
      consistent with literature.

PMID- 21083926
TI  - Occult hepatitis B infection in egyptian chronic hepatitis C patients:
      prevalence, impact on pegylated interferon/ribavirin therapy.
AB  - BACKGROUND: Chronic HCV infection combined with occult hepatitis B infection has
      been associated with liver enzymes flare, advanced hepatic fibrosis and
      cirrhosis, poor response to standard interferon-alpha, and increased risk of HCC.
      This study aimed to elucidate the prevalence of occult hepatitis B infection in
      Egyptian chronic HCV patients, and to clarify its role in non-response of those
      patients to pegylated interferon/ribavirin therapy. This study enrolled 155
      consecutive chronic HCV patients under pegylated interferon/ribavirin therapy.
      All patients were exposed to clinical assessment, biochemical, histological and
      virological examinations. HBV parameters (HBV DNA, anti-HBc, anti-HBs) and
      patients' response status to the combination therapy were determined. RESULTS: In
      this study, occult hepatitis B infection occurs in 3.9% of Egyptian chronic HCV
      patients; tends to affect younger age patients, associated with higher base line
      HCV viral load, less hepatic fibrosis than monoinfected patients. This occult
      hepatitis B infection is not a statistically significant cause of non-response to
      pegylated interferon/ribavirin therapy. Anti-HBs was not associated with any
      biochemical, histological or virological abnormalities in those patients,
      contrary to low response rate to therapy and higher HCV viral load that was
      observed with anti-HBc. CONCLUSIONS: Detection of HBV DNA in HBsAg negative
      chronic HCV patients plays a non significant role in non-response of Egyptian
      patients to pegylated interferon/ribavirin therapy.

PMID- 21083927
TI  - Statistical design of personalized medicine interventions: the Clarification of
      Optimal Anticoagulation through Genetics (COAG) trial.
AB  - BACKGROUND: There is currently much interest in pharmacogenetics: determining
      variation in genes that regulate drug effects, with a particular emphasis on
      improving drug safety and efficacy. The ability to determine such variation
      motivates the application of personalized drug therapies that utilize a patient's
      genetic makeup to determine a safe and effective drug at the correct dose. To
      ascertain whether a genotype-guided drug therapy improves patient care, a
      personalized medicine intervention may be evaluated within the framework of a
      randomized controlled trial. The statistical design of this type of personalized
      medicine intervention requires special considerations: the distribution of
      relevant allelic variants in the study population; and whether the
      pharmacogenetic intervention is equally effective across subpopulations defined
      by allelic variants. METHODS: The statistical design of the Clarification of
      Optimal Anticoagulation through Genetics (COAG) trial serves as an illustrative
      example of a personalized medicine intervention that uses each subject's genotype
      information. The COAG trial is a multicenter, double blind, randomized clinical
      trial that will compare two approaches to initiation of warfarin therapy:
      genotype-guided dosing, the initiation of warfarin therapy based on algorithms
      using clinical information and genotypes for polymorphisms in CYP2C9 and VKORC1;
      and clinical-guided dosing, the initiation of warfarin therapy based on
      algorithms using only clinical information. RESULTS: We determine an absolute
      minimum detectable difference of 5.49% based on an assumed 60% population
      prevalence of zero or multiple genetic variants in either CYP2C9 or VKORC1 and an
      assumed 15% relative effectiveness of genotype-guided warfarin initiation for
      those with zero or multiple genetic variants. Thus we calculate a sample size of
      1238 to achieve a power level of 80% for the primary outcome. We show that
      reasonable departures from these assumptions may decrease statistical power to
      65%. CONCLUSIONS: In a personalized medicine intervention, the minimum detectable
      difference used in sample size calculations is not a known quantity, but rather
      an unknown quantity that depends on the genetic makeup of the subjects enrolled.
      Given the possible sensitivity of sample size and power calculations to these key
      assumptions, we recommend that they be monitored during the conduct of a
      personalized medicine intervention. TRIAL REGISTRATION: clinicaltrials.gov:
      NCT00839657.

PMID- 21083928
TI  - Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome
      analysis.
AB  - BACKGROUND: Transcriptome analysis was applied to characterize the physiological
      activities of Pseudomonas aeruginosa grown for three days in drip-flow biofilm
      reactors. Conventional applications of transcriptional profiling often compare
      two paired data sets that differ in a single experimentally controlled variable.
      In contrast this study obtained the transcriptome of a single biofilm state,
      ranked transcript signals to make the priorities of the population manifest, and
      compared rankings for a priori identified physiological marker genes between the
      biofilm and published data sets. RESULTS: Biofilms tolerated exposure to
      antibiotics, harbored steep oxygen concentration gradients, and exhibited
      stratified and heterogeneous spatial patterns of protein synthetic activity.
      Transcriptional profiling was performed and the signal intensity of each
      transcript was ranked to gain insight into the physiological state of the biofilm
      population. Similar rankings were obtained from data sets published in the GEO
      database http://www.ncbi.nlm.nih.gov/geo. By comparing the rank of genes selected
      as markers for particular physiological activities between the biofilm and
      comparator data sets, it was possible to infer qualitative features of the
      physiological state of the biofilm bacteria. These biofilms appeared, from their
      transcriptome, to be glucose nourished, iron replete, oxygen limited, and growing
      slowly or exhibiting stationary phase character. Genes associated with
      elaboration of type IV pili were strongly expressed in the biofilm. The biofilm
      population did not indicate oxidative stress, homoserine lactone mediated quorum
      sensing, or activation of efflux pumps. Using correlations with transcript ranks,
      the average specific growth rate of biofilm cells was estimated to be 0.08 h(-1).
      CONCLUSIONS: Collectively these data underscore the oxygen-limited, slow-growing
      nature of the biofilm population and are consistent with antimicrobial tolerance
      due to low metabolic activity.

PMID- 21083929
TI  - Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic
      children.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by
      difficulties in communication, cognitive and learning deficits, as well as
      stereotypic behaviors. For the majority of cases there are no reliable biomarkers
      or distinct pathogenesis. However, increasing evidence indicates ASD may be
      associated with some immune dysregulation, and may have a neuroimmune component.
      We recently showed that the peptide neurotensin (NT) is increased in autistic
      children. We now show that NT induces release of extracellular mitochondrial DNA
      (mtDNA) that could act as "autoimmune" trigger. We further show that serum from
      young autistic patients contains mtDNA (n = 20; cytochrome B, p = 0.0002 and 7S,
      p = 0.006), and anti-mitochondrial antibody Type 2 (n = 14; p = 0.001) as
      compared to normally developing, unrelated controls (n = 12). Extracellular blood
      mtDNA and other components may characterize an autistic endophenotype and may
      contribute to its pathogenesis by activating autoimmune responses.

PMID- 21083930
TI  - Integration of deep transcriptome and proteome analyses reveals the components of
      alkaloid metabolism in opium poppy cell cultures.
AB  - BACKGROUND: Papaver somniferum (opium poppy) is the source for several
      pharmaceutical benzylisoquinoline alkaloids including morphine, the codeine and
      sanguinarine. In response to treatment with a fungal elicitor, the biosynthesis
      and accumulation of sanguinarine is induced along with other plant defense
      responses in opium poppy cell cultures. The transcriptional induction of alkaloid
      metabolism in cultured cells provides an opportunity to identify components of
      this process via the integration of deep transcriptome and proteome databases
      generated using next-generation technologies. RESULTS: A cDNA library was
      prepared for opium poppy cell cultures treated with a fungal elicitor for 10 h.
      Using 454 GS-FLX Titanium pyrosequencing, 427,369 expressed sequence tags (ESTs)
      with an average length of 462 bp were generated. Assembly of these sequences
      yielded 93,723 unigenes, of which 23,753 were assigned Gene Ontology annotations.
      Transcripts encoding all known sanguinarine biosynthetic enzymes were identified
      in the EST database, 5 of which were represented among the 50 most abundant
      transcripts. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of total
      protein extracts from cell cultures treated with a fungal elicitor for 50 h
      facilitated the identification of 1,004 proteins. Proteins were fractionated by
      one-dimensional SDS-PAGE and digested with trypsin prior to LC-MS/MS analysis.
      Query of an opium poppy-specific EST database substantially enhanced peptide
      identification. Eight out of 10 known sanguinarine biosynthetic enzymes and many
      relevant primary metabolic enzymes were represented in the peptide database.
      CONCLUSIONS: The integration of deep transcriptome and proteome analyses provides
      an effective platform to catalogue the components of secondary metabolism, and to
      identify genes encoding uncharacterized enzymes. The establishment of
      corresponding transcript and protein databases generated by next-generation
      technologies in a system with a well-defined metabolite profile facilitates an
      improved linkage between genes, enzymes, and pathway components. The proteome
      database represents the most relevant alkaloid-producing enzymes, compared with
      the much deeper and more complete transcriptome library. The transcript database
      contained full-length mRNAs encoding most alkaloid biosynthetic enzymes, which is
      a key requirement for the functional characterization of novel gene candidates.

PMID- 21083931
TI  - Effects of site-directed mutagenesis of mglA on motility and swarming of
      Myxococcus xanthus.
AB  - BACKGROUND: The mglA gene from the bacterium Myxococcus xanthus encodes a 22kDa
      protein related to the Ras superfamily of monomeric GTPases. MglA is required for
      the normal function of A-motility (adventurous), S-motility (social), fruiting
      body morphogenesis, and sporulation. MglA and its homologs differ from all
      eukaryotic and other prokaryotic GTPases because they have a threonine (Thr78) in
      place of the highly conserved aspartate residue of the consensus PM3 (phosphate
      magnesium binding) region. To identify residues critical for MglA function or
      potential protein interactions, and explore the function of Thr78, the phenotypes
      of 18 mglA mutants were characterized. RESULTS: Nine mutants, with mutations
      predicted to alter residues that bind the guanine base or coordinate magnesium,
      did not produce detectable MglA. As expected, these mutants were mot- dev-
      because MglA is essential for these processes. Of the remaining nine mutants,
      seven showed a wild-type distribution pattern for MglA but fell into two
      categories with regard to function. Five of the seven mutants exhibited mild
      phenotypes, but two mutants, T78D and P80A, abolished motility and development.
      The localization pattern of MglA was abolished in two mutants that were mot- spo-
      and dev-. These two mutants were predicted to alter surface residues at Asp52 and
      Thr54, which suggests that these residues are critical for proper localization
      and may define a protein interaction site. Improving the consensus match with Ras
      at Thr78 abolished function of MglA. Only the conservative serine substitution
      was tolerated at this position. Merodiploid constructs revealed that a subset of
      alleles, including mglAD52A, were dominant and also illustrated that changing the
      balance of MglA and its co-transcribed partner, MglB, affects A-motility.
      CONCLUSION: Our results suggest that GTP binding is critical for stability of
      MglA because MglA does not accumulate in mutants that cannot bind GTP. The
      threonine in PM3 of MglA proteins represents a novel modification of the highly
      conserved GTPase consensus at this position. The requirement for a hydroxyl group
      at this position may indicate that MglA is subject to modification under certain
      conditions. Proper localization of MglA is critical for both motility and
      development and likely involves protein interactions mediated by residues Asp52
      and Thr54.

PMID- 21083932
TI  - Gene expression profile of the skin in the 'hairpoor' (HrHp) mice by microarray
      analysis.
AB  - BACKGROUND: The transcriptional cofactor, Hairless (HR), acts as one of the key
      regulators of hair follicle cycling; the loss of function mutations is the cause
      of the expression of the hairless phenotype in humans and mice. Recently, we
      reported a new Hr mutant mouse called 'Hairpoor' (Hr(Hp)). These mutants harbor a
      gain of the function mutation, T403A, in the Hr gene. This confers the
      overexpression of HR and Hr(Hp) is an animal model of Marie Unna hereditary
      hypotrichosis in humans. In the present study, the expression profile of
      Hr(Hp)/Hr(Hp) skin was investigated using microarray analysis to identify genes
      whose expression was affected by the overexpression of HR. RESULTS: From 45,282
      mouse probes, differential expressions in 43 (>2-fold), 306 (>1.5-fold), and 1861
      genes (>1.2-fold) in skin from Hr(Hp)/Hr(Hp) mice were discovered and compared
      with skin from wild-type mice. Among the 1861 genes with a > 1.2-fold increase in
      expression, further analysis showed that the expression of eight genes known to
      have a close relationship with hair follicle development, ascertained by
      conducting real-time PCR on skin RNA produced during hair follicle morphogenesis
      (P0-P14), indicated that four genes, Wif1, Casp14, Krt71, and Sfrp1, showed a
      consistent expression pattern with respect to HR overexpression in vivo.
      CONCLUSION: Wif1 and Casp14 were found to be upregulated, whereas Krt71 and Sfrp1
      were downregulated in cells overexpressing HR in transient transfection
      experiments on keratinocytes, suggesting that HR may transcriptionally regulate
      these genes. Further studies are required to understand the mechanism of this
      regulation by the HR cofactor.

PMID- 21083933
TI  - A single-amino-acid substitution in the HA protein changes the replication and
      pathogenicity of the 2009 pandemic A (H1N1) influenza viruses in vitro and in
      vivo.
AB  - BACKGROUND: The novel pandemic A (H1N1) virus was first identified in Mexico in
      April 2009 and since then it spread world wide over a short period of time.
      Although the virus infection is generally associated with mild disease and a
      relatively low mortality, it is projected that mutations in specific regions of
      the viral genome, especially within the receptor binding domain of the
      hemagglutinin (HA) protein could result in more virulent virus stains, leading to
      a more severe pandemic. RESULTS: Here, we found that a single amino acid
      substitution of Asp-to-Gly at position 222 in the HA protein of the A (H1N1)
      virus occurred after two passage propagation in the allantoic cavities of chicken
      embryonated eggs, and this single residue variation dramatically increased the
      viral replication ability in MDCK cells and pathogenicity in BALB/c mice.
      CONCLUSIONS: A substitution of Asp-to-Gly at position 222 in the HA protein was
      prone to occur under positive selection pressures, and this single amino acid
      mutation could dramatically increase the virus replication ability in vitro and
      pathogenicity in vivo. Our finding offers a better understanding of the
      transmission and evolution of the 2009 pandemic A (H1N1) virus and brings
      attention to further potentially severe influenza pandemic that may result from
      cross-host evolution of the influenza viruses.

PMID- 21083934
TI  - Using principal component analysis to develop a single-parameter screening tool
      for metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MS) is an important current public health problem
      faced worldwide. To prevent an "epidemic" of this syndrome, it is important to
      develop an easy single-parameter screening technique (such as waist circumference
      (WC) determination recommended by the International Diabetes Federation).
      Previous studies proved that age is a chief factor corresponding to central
      obesity. We intended to present a new index based on the linear combination of
      body mass index, and age, which could enhance the area under the receiver
      operating characteristic curves (AUCs) for assessing the risk of MS. METHODS: The
      labour law of the Association of Labor Standard Law, Taiwan, states that
      employers and employees are respectively obligated to offer and receive routine
      health examination periodically. Secondary data analysis and subject's biomarkers
      among five high-tech factories were used in this study between 2007 and 2008 in
      northern Taiwan. The subjects included 4712 males and 4196 females. The first
      principal component score (FPCS) and equal-weighted average (EWA) were determined
      by statistical analysis. RESULTS: Most of the metabolic and clinical
      characteristics were significantly higher in males than in females, except high
      density lipoprotein cholesterol level. The older group (>45 years) had
      significantly lower values for height and high-density lipoprotein cholesterol
      level than the younger group. The AUCs of FPCS and EWA were significantly larger
      than those of WC and waist-to-height ratio. The low specificities of EWA and FPCS
      were compensated for by their substantially high sensitivities. FPCS >= 0.914
      (15.4%) and EWA >= 8.8 (6.3%) were found to be the most prevalent cut off points
      in males and females, respectively. CONCLUSIONS: The Bureau of Health Promotion,
      Department of Health, Taiwan, had recommended the use of WC >= 90 cm for males
      and >= 80 cm for females as singular criteria for the determination of central
      obesity instead of multiple parameters. The present investigation suggests that
      FPCS or EWA is a good predictor of MS among the Taiwanese. However, the use of
      FPCS is not computationally feasible in practice. Therefore, we suggest that EWA
      be used in clinical practice as a simple parameter for the identification of
      those at risk of MS.

PMID- 21083935
TI  - Reanalyze unassigned reads in Sanger based metagenomic data using conserved gene
      adjacency.
AB  - BACKGROUND: Investigation of metagenomes provides greater insight into uncultured
      microbial communities. The improvement in sequencing technology, which yields a
      large amount of sequence data, has led to major breakthroughs in the field.
      However, at present, taxonomic binning tools for metagenomes discard 30-40% of
      Sanger sequencing data due to the stringency of BLAST cut-offs. In an attempt to
      provide a comprehensive overview of metagenomic data, we re-analyzed the
      discarded metagenomes by using less stringent cut-offs. Additionally, we
      introduced a new criterion, namely, the evolutionary conservation of adjacency
      between neighboring genes. To evaluate the feasibility of our approach, we re
      analyzed discarded contigs and singletons from several environments with
      different levels of complexity. We also compared the consistency between our
      taxonomic binning and those reported in the original studies. RESULTS: Among the
      discarded data, we found that 23.7 +/- 3.9% of singletons and 14.1 +/- 1.0% of
      contigs were assigned to taxa. The recovery rates for singletons were higher than
      those for contigs. The Pearson correlation coefficient revealed a high degree of
      similarity (0.94 +/- 0.03 at the phylum rank and 0.80 +/- 0.11 at the family
      rank) between the proposed taxonomic binning approach and those reported in
      original studies. In addition, an evaluation using simulated data demonstrated
      the reliability of the proposed approach. CONCLUSIONS: Our findings suggest that
      taking account of conserved neighboring gene adjacency improves taxonomic
      assignment when analyzing metagenomes using Sanger sequencing. In other words,
      utilizing the conserved gene order as a criterion will reduce the amount of data
      discarded when analyzing metagenomes.

PMID- 21083936
TI  - Factors influencing overweight children's commencement of and continuation in a
      resistance training program.
AB  - BACKGROUND: In light of the child overweight and obesity problem in Australia,
      resistance training programs have been trialled as an innovative way of assisting
      children increase lean body mass and reduce body fat. The purpose of this study
      was to investigate the factors influencing overweight children's participation in
      a resistance training trial program. METHOD: Parent-child pairs who participated
      in the trial program were invited to take part in a follow-up individual
      interview to discuss their program experiences. In total, 22 semi-structured
      interviews were conducted with 11 parent-child pairs. RESULTS: The factors found
      to be most relevant to program commencement among parents were a desire for their
      child to lose weight and gain confidence, the proximity of the venue, and no cost
      for participation. For children, the most relevant factors were the opportunity
      to build strength and improve fitness and having supportive parents who
      facilitated program initiation. The factors most relevant to continuation for
      parents were the quality of the program management, being able to stay for the
      sessions, the child's improved weight status, coordination, and confidence, and
      no cost for participation. Weight loss and improved confidence were also
      motivators for continuation among the children, along with pleasant social
      interaction with peers and trainers and ongoing parental support. CONCLUSION:
      Different factors variably influence program commencement and program
      continuation in both parents and children. This has important implications for
      future interventions that aim to successfully recruit and retain intervention
      participants.

PMID- 21083937
TI  - Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis.
AB  - BACKGROUND: Glucocorticoid (GC) resistance is frequently seen in acute
      lymphoblastic leukemia of T-cell lineage (T-ALL). In this study we investigate
      the potential and mechanism of using rapamycin to restore the sensitivity of GC
      resistant T-ALL cells to dexamethasone (Dex) treatment. METHODS: Cell
      proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)- 2,5
      diphenyltetrazolium bromide (MTT) assay. Fluorescence-activated cell sorting
      (FACS) analysis was used to analyze apoptosis and cell cycles. Western blot
      analysis was performed to test the expression of the downstream effector proteins
      of mammalian target of rapamycin (mTOR), the cell cycle regulatory proteins, and
      apoptosis associated proteins. RESULTS: 10 nM rapamycin markedly increased GC
      sensitivity in GC-resistant T-ALL cells and this effect was mediated, at least in
      part, by inhibition of mTOR signaling pathway. Cell cycle arrest was associated
      with modulation of G1-S phase regulators. Both rapamycin and Dex can induce up
      regulation of cyclin-dependent kinase (CDK) inhibitors of p21 and p27 and co
      treatment of rapamycin with Dex resulted in a synergistic induction of their
      expressions. Rapamycin did not obviously affect the expression of cyclin A,
      whereas Dex induced cyclin A expression. Rapamycin prevented Dex-induced
      expression of cyclin A. Rapamycin had a stronger inhibition of cyclin D1
      expression than Dex. Rapamycin enhanced GC-induced apoptosis and this was not
      achieved by modulation of glucocorticoid receptor (GR) expression, but
      synergistically up-regulation of pro-apoptotic proteins like caspase-3, Bax, and
      Bim, and down-regulation of anti-apoptotic protein of Mcl-1. CONCLUSION: Our data
      suggests that rapamycin can effectively reverse GC resistance in T-ALL and this
      effect is achieved by inducing cell cycles arrested at G0/G1 phase and activating
      the intrinsic apoptotic program. Therefore, combination of mTOR inhibitor
      rapamycin with GC containing protocol might be an attracting new therapeutic
      approach for GC resistant T-ALL patients.

PMID- 21083939
TI  - Characteristics in patients with headache in an outpatient clinic in Japan.
AB  - BACKGROUND: Little is known about the prevalence of primary and secondary
      headache in clinics in Japan. The aim of this study is to characterize patients
      with headache in an outpatient unit where primary care physicians are working in
      Japan. METHODS: Consecutive outpatients who newly visited the Department of
      General Medicine, Asahikawa Medical College Hospital, Asahikawa, Japan between
      April 2005 and March 2009 were analyzed. Each parameter such as age, sex or
      diagnosis was investigated. RESULTS: Out of 4693 patients, 418 patients visited
      to our department because of headache. Primary headache was found in 167 patients
      (39.9%). The rate of tension-type headache (TTH) (30.8%) was highest, followed by
      migraine (9.1%). Approximately 3 times higher rate of migraine was observed in
      female patients when compared with male patients. In female patients, migraine
      was observed more frequently in younger patients. On the other hands, TTH was
      observed in almost all aged patients in males and females, and the rate of TTH
      peaks between the ages of 40 and 49 years in both sex. The present study also
      demonstrated that 8.4% of patients who chiefly complained of headache had been
      diagnosed as depression while 1.7% of remained patients had been diagnosed as
      depression, indicating 5-times higher rate of depression in patients with
      headache. CONCLUSION: All these results suggest that primary headache, especially
      TTH, is highly observed and depression should be considered in patients with
      headache in an outpatient clinic where primary care physicians are working in
      Japan.

PMID- 21083938
TI  - Combining target enrichment with barcode multiplexing for high throughput SNP
      discovery.
AB  - BACKGROUND: The primary goal of genetic linkage analysis is to identify genes
      affecting a phenotypic trait. After localisation of the linkage region, efficient
      genetic dissection of the disease linked loci requires that functional variants
      are identified across the loci. These functional variations are difficult to
      detect due to extent of genetic diversity and, to date, incomplete cataloguing of
      the large number of variants present both within and between populations.
      Massively parallel sequencing platforms offer unprecedented capacity for variant
      discovery, however the number of samples analysed are still limited by cost per
      sample. Some progress has been made in reducing the cost of resequencing using
      either multiplexing methodologies or through the utilisation of targeted
      enrichment technologies which provide the ability to resequence genomic areas of
      interest rather that full genome sequencing. RESULTS: We developed a method that
      combines current multiplexing methodologies with a solution-based target
      enrichment method to further reduce the cost of resequencing where region
      specific sequencing is required. Our multiplex/enrichment strategy produced high
      quality data with nominal reduction of sequencing depth. We undertook a
      genotyping study and were successful in the discovery of novel SNP alleles in all
      samples at uniplex, duplex and pentaplex levels. CONCLUSION: Our work describes
      the successful combination of a targeted enrichment method and index barcode
      multiplexing to reduce costs, time and labour associated with processing large
      sample sets. Furthermore, we have shown that the sequencing depth obtained is
      adequate for credible SNP genotyping analysis at uniplex, duplex and pentaplex
      levels.

PMID- 21083940
TI  - Myocardial fibrosis in desmin-related hypertrophic cardiomyopathy.
AB  - Desmin-related myopathy (DRM) is known to cause different types of
      cardiomyopathy. Late gadolinium enhancement cardiovascular magnetic resonance
      (CMR) has been shown to identify fibrosis in ischemic and non-ischemic
      cardiomyopathies. We present a rare case of desmin-related hypertrophic
      cardiomyopathy, CMR revealed fibrosis in the lateral wall of the left ventricle.
      CMR is superior to conventional echocardiography for the detection of myocardial
      fibrosis in desmin-related cardiomyopathy, which may be useful to detect early
      cardiac involvement and predict the patient prognosis.

PMID- 21083941
TI  - Proteomic analysis of streptomycin resistant and sensitive clinical isolates of
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Streptomycin (SM) is a broad spectrum antibiotic and is an important
      component of any anti-tuberculosis therapy regimen. Several mechanisms have been
      proposed to explain the emergence of resistance but still our knowledge is
      inadequate. Proteins form a very complex network and drugs are countered by their
      modification/efflux or over expression/modification of targets. As proteins
      manifest most of the biological processes, these are attractive targets for
      developing drugs, immunodiagnostics or therapeutics. The aim of present study was
      to analyze and compare the protein profile of whole cell extracts from
      Mycobacterium tuberculosis clinical isolates susceptible and resistant to SM.
      RESULTS: Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed
      for analyzing the protein profiles. Homology and in silico characterization for
      identified proteins was assessed using BLAST, InterProScan and KEGG database
      searches. Computational studies on the possible interactions between SM and
      identified proteins were carried out by a battery of online servers and
      softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On
      comparing 2DE patterns, nine proteins were found consistently overexpressed in SM
      resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c,
      Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. In silico docking analysis showed
      significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non
      essential (Rv1240, Rv3075c and Rv2031c) genes. CONCLUSIONS: The computational
      results suggest high protein binding affinity of SM and suggested many possible
      interactions between identified proteins and the drug. Bioinformatic analysis
      proves attributive for analysis of diversity of proteins identified by whole
      proteome analysis. In-depth study of the these proteins will give an insight into
      probable sites of drug action other than established primary sites and hence may
      help in search of novel chemotherapeutic agents at these new sites as inhibitors.

PMID- 21083943
TI  - MetNetAPI: A flexible method to access and manipulate biological network data
      from MetNet.
AB  - BACKGROUND: Convenient programmatic access to different biological databases
      allows automated integration of scientific knowledge. Many databases support a
      function to download files or data snapshots, or a webservice that offers "live"
      data. However, the functionality that a database offers cannot be represented in
      a static data download file, and webservices may consume considerable
      computational resources from the host server. RESULTS: MetNetAPI is a versatile
      Application Programming Interface (API) to the MetNetDB database. It abstracts,
      captures and retains operations away from a biological network repository and
      website. A range of database functions, previously only available online, can be
      immediately (and independently from the website) applied to a dataset of
      interest. Data is available in four layers: molecular entities, localized
      entities (linked to a specific organelle), interactions, and pathways. Navigation
      between these layers is intuitive (e.g. one can request the molecular entities in
      a pathway, as well as request in what pathways a specific entity participates).
      Data retrieval can be customized: Network objects allow the construction of new
      and integration of existing pathways and interactions, which can be uploaded back
      to our server. In contrast to webservices, the computational demand on the host
      server is limited to processing data-related queries only. CONCLUSIONS: An API
      provides several advantages to a systems biology software platform. MetNetAPI
      illustrates an interface with a central repository of data that represents the
      complex interrelationships of a metabolic and regulatory network. As an
      alternative to data-dumps and webservices, it allows access to a current and
      "live" database and exposes analytical functions to application developers. Yet
      it only requires limited resources on the server-side (thin server/fat client
      setup). The API is available for Java, Microsoft.NET and R programming
      environments and offers flexible query and broad data- retrieval methods. Data
      retrieval can be customized to client needs and the API offers a framework to
      construct and manipulate user-defined networks. The design principles can be used
      as a template to build programmable interfaces for other biological databases.
      The API software and tutorials are available at http://www.metnetonline.org/api.

PMID- 21083942
TI  - Effects of GnRH agonist treatment on steroidogenesis and folliculogenesis in the
      ovary of cyclic mice.
AB  - BACKGROUND: GnRH analogs (both agonist and antagonist) have been extensively used
      for clinical applications, following the discovery of its direct effects on
      ovary. With regard to the direct actions of GnRH agonist on ovary, conflicting
      data are reported. The mechanism through which GnRH agonist affect gonadal
      functions is still obscure. The aim of present study was thus to investigate the
      effects of treatment with different doses of GnRH agonist, in vivo and in vitro,
      on morphological, physiological and functional changes in the ovary of cyclic
      mice. METHODS: To find out the effect of GnRH agonist on ovarian activity, cyclic
      mice were treated with different doses for 8 days and its effect on
      folliculogenesis (morphological changes in follicle, Estrogen receptor,
      progesterone receptor), steroidogenesis (circulating progesterone level, StAR, LH
      receptor, 3beta-HSD), luteinization (Morphology of corpus luteum) and apoptosis
      (caspase-3, PARP) were observed. To find the in vitro effects of GnRH agonist
      with or without LH on ovary of mice, changes in the expression of LH-receptor,
      estrogen receptor, progesterone receptor, 3beta-HSD in the ovary and progesterone
      level in the culture media were investigated. RESULTS: GnRH agonist treatment
      produced significant changes in ovarian mass, circulating steroids level and
      ovarian follicular development, steroidogenesis and apoptosis in the mice. GnRH
      agonist also caused dose dependent histological changes in follicular development
      and luteinization. The mice treated with different doses of GnRH agonist showed
      biphasic effects on steroid synthesis due to its effects on ovarian expression of
      LH-receptor, StAR, and 3beta -hydroxysteroid dehydrogenase proteins. The high
      dose showed stimulatory effect, whereas pharmacological dose showed inhibitory
      effect on ovarian follicular development and steroidogenesis. The in vitro study
      generally showed inhibitory effects of GnRH agonist on ovarian activities, which
      may be reversed by the presence of LH. CONCLUSION: Both inhibitory and
      stimulatory effects found in the present study suggest that GnRH agonist is a
      versatile tool in the therapy of a variety of gynecological and non-gynecological
      conditions. This study suggests that the outcome of direct effect of GnRH-ag on
      ovary depends on LH-responsiveness.

PMID- 21083944
TI  - [An immunocompromised host with a fever].
AB  - A 61-year-old woman with a hepatocellular carcinoma was admitted to the hospital
      for transplantation of the liver. She had a compromised immune system and
      developed a aspergillus pneumonia. The patient eventually died due to sepsis and
      multiple organ failure.

PMID- 21083945
TI  - ['Dropped nucleus' on cataract extraction].
AB  - In 0.1% to 1% of cases cataract extraction is complicated by luxated lens
      fragments, also known as 'dropped nucleus'. Dropped nucleus can lead to severe
      complications such as glaucoma or retinal detachment. After incomplete cataract
      extraction visual acuity is poor. Although a few patients with dropped nucleus
      may heal with medication alone, pars plana vitrectomy is indicated in most of
      cases. Pars plana vitrectomy entails the removal of luxated lens fragments and
      placement of an artificial lens if necessary. It is recommended that pars plana
      vitrectomy be performed within one to two weeks after cataract extraction. It
      allows recovery of visual acuity in most of cases. It is important that cataract
      patients should be informed about the possibility of a dropped nucleus before the
      extraction.

PMID- 21083947
TI  - [Experience with euthanasia since 2007. Analysis of problems with execution].

PMID- 21083946
TI  - [Recovery from blindness following smallpox or measles: Dutch miracle stories,
      14th-18th century].
AB  - Over recent decades, stories of miracles dating from 1380-1726 have been
      transcribed and are now generally available. These texts only contain a limited
      amount of medical information. This article closely examines the stories of being
      cured of blindness after being infected by smallpox or measles. Most of these
      stories concern children. Eleven of a total of 1700 stories that took place
      during the above-mentioned period of time concern this type of miracle. The
      article examines the possible relationship between these miracles and a lack of
      vitamin A.

PMID- 21083948
TI  - [Could it be a little less? Let the dose of thiopental in euthanasia depend on
      the body weight].
AB  - The Dutch 'euthanasia and assisted suicide' practice guideline advises using 2000
      mg thiopental to induce coma, followed by a muscle relaxant to cause death by
      respiratory paralysis. However, when a doctor administers such a high dose of
      thiopental as a bolus injection to a cachectic patient, there is a high
      likelihood of immediate death and other side effects, which can be distressing
      for the family. Doctors who administered less than 2000 mg have been reprimanded
      for not working according to current standards. Arguments are given concerning in
      which circumstances it is reasonable to use the advised dose of 2000 mg of
      thiopental and when to use less thiopental to induce coma by direct intravenous
      injection. The author suggests that it may be better to adjust the dose of
      thiopental according to the body weight of the patient. The current practice
      guideline needs revision.

PMID- 21083949
TI  - [Fire by spontaneous combustion of oxygen cylinders].
AB  - The use of medicinal oxygen can be dangerous. The spontaneous combustion of an
      oxygen cylinder was the cause of a fire in an operating theatre and an emergency
      medical service. The fire developed after turning on the gas main while the flow
      supply valve was already open. Not opening the pressure reduction valve while the
      oxygen flow supply valve is open can prevent this type of fire. Information from
      the contractor shows that the probability of such an incident is 1 in a million.

PMID- 21083950
TI  - [Treatment of drooling in patients with parkinsonism].
AB  - Between 50% and 60% of patients with parkinsonism suffer from severe drooling
      (sialorrhoea). Sialorrhoea is a major social problem with medical risks as well,
      e.g. aspiration pneumonia. Sialorrhoea is not caused by increased production of
      saliva, but by impaired swallowing, leading to storage of saliva in the anterior
      part of the mouth. Sialorrhoea can be treated by anticholinergics, botulinum
      toxin injections, surgery and radiotherapy of the salivary glands. The optimal
      treatment of sialorrhoea needs to be determined individually, for which a
      decision tree is available.

PMID- 21083951
TI  - [Recurrent rhabdomyolysis: screening for underlying disease].
AB  - Rhabdomyolysis is a rare potentially dangerous syndrome resulting from the
      dissolution of skeletal muscle fibres. An isolated attack of rhabdomyolysis can
      have various causes, such as trauma, hyperpyrexia, infections, electrolyte
      imbalances, seizures, severe exertion, and drugs or substance abuse or a
      combination of these. Recurrent episodes and/or a family history of
      rhabdomyolysis is more likely caused by an underlying genetic defect. Three
      patients with rhabdomyolysis are described. One patient had an isolated episode
      due to excessive exercise. The other patients had a medical history or
      accompanying symptoms that suggested an underlying genetic metabolic myopathy
      confirmed in both by DNA analysis. An algorithm on when and how to screen for
      underlying genetic diseases is presented. Diagnosis of these genetic diseases is
      important for adequate counselling and dietary measures to prevent future
      episodes.

PMID- 21083952
TI  - [The healing of a lame person in Betesda].
AB  - In 1575 Pieter Aertsen (1508?-1575) painted the biblical story of the healing of
      a lame man at Bethesda (John 5:1-9). At closer inspection, the painting reveals
      that the invalid is suffering from foot drop as well.

PMID- 21083953
TI  - [A man with a painful right hand].
AB  - A young man visited the Emergency Department with a painful right hand after
      punching his fist against a wall. He suffered a luxation in the fifth
      carpometacarpal joint and a fracture at the base of the fourth metacarpal bone
      which were successfully treated by reposition and plaster bandage for 4 weeks.

PMID- 21083954
TI  - [A man with a painful chest after frequent vomiting].
AB  - A 60-year-old man presented with chest pain and weight loss, starting after a
      period of vomiting. Contrast radiography of the esophagus revealed an esophageal
      pleural fistula. The patient was successfully treated by stent placement.

PMID- 21083955
TI  - [Antitumour effects of bisphosphonates in breast cancer].
AB  - Pre-clinical and clinical studies increasingly suggest that the most potent
      nitrogen-containing bisphosphonates have antitumour effects. Bisphosphonates
      inhibit osteoclast-mediated bone resorption, and can thus delay the spread of
      skeletal metastases. Bisphosphonates might also inhibit tumour growth outside the
      skeleton by inducing apoptosis and inhibiting proliferation, adhesion, invasion,
      and angiogenesis of tumour cells. Recent trials suggest a possible synergistic
      antitumour effect between bisphosphonates and chemotherapy. A mechanism of action
      for bisphosphonates that could explain their possible antitumour effect and their
      synergy with chemotherapy is speculative and demands further investigation. The
      role of bisphosphonates in primary neoadjuvant treatment of breast cancer is
      promising, but must be further investigated.

PMID- 21083956
TI  - [Unexceptional symptoms as expression of MELAS].
AB  - An 11-year-old girl and a 25-year-old woman were both initially referred to a
      neurologist with 'common' neurological problems: The girl suffered from tics, and
      later epilepsy, and her serum lactate concentration was elevated. She had
      unilateral hyperintensity of the left cerebral cortex and later developed
      diabetes mellitus. The woman had muscle weakness, diabetes mellitus and ptosis.
      In both patients, the problems turned out to be an expression of MELAS
      (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes). The first patient died at 18 years of age during an epileptic seizure
      with severe metabolic disturbances. The second patient developed bilateral
      perceptive hearing loss, epilepsy and cardiomyopathy and she was repeatedly
      admitted to hospital with stroke-like episodes. She died at 46 years of age. Both
      patients had the MELAS A3243G point mutation. MELAS is a maternally inherited
      mitochondrial disorder. The age of onset and symptoms are highly variable, even
      within one family. To date there are no curative treatment options for the
      disease. Diagnosing MELAS is important though, for optimising the treatment of
      the individual symptoms and genetic counselling.

PMID- 21083957
TI  - [Endoscopic removal of large colonic lipomas].
AB  - Lipomas are benign tumours that are sometimes found in the colon, where they may
      cause symptoms through constriction and blood loss. Until recently, surgical
      removal of large lipomas was the therapy of choice, because of the danger of
      bleeding and perforation during endoscopy. The endoloop (PolyLoop, Olympus
      Medical Systems Corp., Tokyo, Japan), by use of which the base of the lipoma is
      constricted by a nylon loop, has changed this approach. We describe the
      successful removal of a large lipoma located in the ascending colon in 2 patients
      who were referred shortly after one another to the endoscopy department of our
      hospital. This endoscopic technique should be considered for removal of large
      pedunculated polyps in the intestine.

PMID- 21083958
TI  - [Open lateral clavicle resection in acromioclavicular osteoarthritis: favourable
      results after 1 year].
AB  - OBJECTIVE: To determine the follow-up outcomes of open lateral clavicle resection
      1 year postoperatively in patients with acromioclavicular osteoarthritis. The
      operation involves resection of a small part of the lateral clavicle. DESIGN:
      Prospective descriptive. METHOD: Data were collected from all patients who had
      undergone an open lateral clavicle resection in the period July 1999 to June 2008
      and who were examined preoperatively and 1 year postoperatively. This concerned
      23 operations in 22 patients. The Constant score for the functionality of the
      shoulder was determined and visual analogue scales (VAS) were used to determine
      the pain and satisfaction concerning the operated shoulder. The results were
      evaluated with the paired t-test and the non-parametric Wilcoxon test. RESULTS:
      The mean length of the lateral clavicle resection was 7.8 mm. Preoperatively the
      mean Constant score was 64 (SD: 14) and 1 year after the operation 86 (SD: 14; p
      < 0.001). Ninety-one percent had an increase in the postoperative Constant score
      compared with the preoperative score. The median VAS score for pain decreased
      from 70 (95% CI: 60-77) preoperatively to 25 (0-48) 1 year postoperatively (p <
      0.001). The median VAS score for satisfaction increased from 40 (40-50)
      preoperatively to 85 (68-100) (p < 0.001). CONCLUSION: The open lateral clavicle
      resection was a treatment option to reduce the symptoms in patients with
      acromioclavicular osteoarthritis in whom conservative treatment and medication
      proved to be insufficient.

PMID- 21083959
TI  - [The midshaft clavicular fracture].
AB  - Traditionally, midshaft clavicular fractures have been treated conservatively.
      However a review of the literature reveals that certain fractures can benefit
      from operative repair. Conservative treatment, preferably in the form of a sling,
      of an undisplaced midshaft clavicular fracture leads to excellent results .
      Dislocated fractures have an increased risk of non-union or malunion.
      Intramedullary fixation can give good results in simple dislocated fractures, but
      does not provide optimal preservation of length and rotation in comminuted
      fractures. Plate osteosynthesis can be used for all clavicular fractures and
      causes a reduction of the relative risk of non-union of 86%. Due to the increased
      risk of non-union or malunion and of a worse functional result, osteosynthesis
      should be considered for patients with dislocated or comminuted midshaft
      clavicular fractures, with due consideration for the patient's expectations and
      lifestyle.

PMID- 21083960
TI  - [Surgery for abdominal aortic aneurysm: open or endovascular repair?].
AB  - Endovascular repair (EVAR) of asymptomatic abdominal aortic aneurysm is an
      attractive alternative to open surgery due to its lower perioperative mortality
      and faster recovery. However, the similar survival rates for open repair and EVAR
      after 2-4 years have raised questions on the durability of EVAR. Recently
      published long term results from the Dutch DREAM trial and the EVAR-1 trial in
      the UK showed that survival rates after open surgery and EVAR remain comparable
      after 6-8 years of follow-up. However, re-intervention rates after EVAR were 30%,
      compared to 10-15% after open surgery. The advantages of EVAR have to be offset
      against a higher rate of re-intervention when deciding on individual treatment.
      Open surgery may be the better option for a younger patient, EVAR for an older
      patient. Long term follow-up of the EVAR-2 trial confirms that in patients with
      severe comorbidity EVAR has no benefit over conservative treatment.

PMID- 21083961
TI  - [Partial breast irradiation (PBI): the therapy of the future?].
AB  - Breast-conserving therapy with radiation therapy of 50 Gy over 5 weeks to the
      entire breast plus a tumour bed boost is the standard treatment for patients with
      early stage breast cancer. Several attempts have been made to lower the treatment
      burden, such as omitting either all radiotherapy or the tumour bed boost, without
      success. Phase III trials are now being carried out to evaluate the treatment of
      the primary tumour area only (PBI). Various methods for selection of patient
      groups and of delivering the radiation dose have been employed. Vaidya et al.
      report the same favourable local recurrence rates following PBI with single dose
      intraoperative radiotherapy as with whole-breast irradiation. As the follow-up
      period so far has been short, long-time results should be awaited.

PMID- 21083962
TI  - Understanding the neuropsychological consequences of deployment stress: a public
      health framework.
AB  - Complaints of neuropsychological dysfunction have emerged among subsets of
      military personnel after almost every major deployment involving western nations
      in recent history. Although deployments have been characterized by a range of
      neural risk factors, psychological stress is common to most prolonged
      deployments. This review uses a public health framework to address associations
      between deployment-related stress and neuropsychological performance.
      Specifically, the review covers mechanisms by which deployment-related
      psychological stress may affect neuropsychological functioning, considers the
      advantages and disadvantages of approaching the question from a public health
      perspective, and discusses how epidemiological research may sort out questions
      regarding course, cause, and effect.

PMID- 21083963
TI  - Comparison of concussive symptoms, cognitive performance, and psychological
      symptoms between acute blast-versus nonblast-induced mild traumatic brain injury.
AB  - Blast-related head injuries are one of the most prevalent injuries among military
      personnel deployed in service of Operation Iraqi Freedom. Although several
      studies have evaluated symptoms after blast injury in military personnel, few
      studies compared them to nonblast injuries or measured symptoms within the acute
      stage after traumatic brain injury (TBI). Knowledge of acute symptoms will help
      deployed clinicians make important decisions regarding recommendations for
      treatment and return to duty. Furthermore, differences more apparent during the
      acute stage might suggest important predictors of the long-term trajectory of
      recovery. This study evaluated concussive, psychological, and cognitive symptoms
      in military personnel and civilian contractors (N = 82) diagnosed with mild TBI
      (mTBI) at a combat support hospital in Iraq. Participants completed a clinical
      interview, the Automated Neuropsychological Assessment Metric (ANAM), PTSD
      Checklist-Military Version (PCL-M), Behavioral Health Measure (BHM), and Insomnia
      Severity Index (ISI) within 72 hr of injury. Results suggest that there are few
      differences in concussive symptoms, psychological symptoms, and neurocognitive
      performance between blast and nonblast mTBIs, although clinically significant
      impairment in cognitive reaction time for both blast and nonblast groups is
      observed. Reductions in ANAM accuracy were related to duration of loss of
      consciousness, not injury mechanism.

PMID- 21083964
TI  - Development of depressive symptoms during early community reintegration after
      traumatic brain injury.
AB  - The early onset of depression following traumatic brain injury (TBI) is
      associated with poorer psychosocial outcomes; however, the direction of this
      relationship is unclear. This study investigated the relationship between
      progress in resuming preinjury lifestyle (transition events), change in perceived
      functioning and level of depressive symptoms at discharge and 3-months
      postdischarge. As part of a prospective longitudinal study of brain injury
      outcomes, 96 consecutively discharged patients with TBI completed measures of
      transition events (Sentinel Events Questionnaire) and perceived functioning (Mayo
      Portland Adaptability Inventory-4 Ability and Adjustment indices) at discharge
      and 3-months follow-up. Level of depressive symptoms was assessed at discharge
      and 3-months follow-up using the Depression Anxiety Stress Scale 21. After
      controlling for age and discharge depressive symptoms, change in perceived
      functioning was found to mediate the relationship between total transition events
      and depressive symptoms at 3-months postdischarge (I2 reduced from .21 to .14),
      with a significant indirect effect observed. The present findings indicate that
      lack of progress in resuming preinjury lifestyle contributes to postdischarge
      depressive symptoms through an influence on perceived functioning, thus providing
      an improved conceptualization of reactive depression in the context of brain
      injury.

PMID- 21083965
TI  - The test of everyday attention reveals significant sustained volitional attention
      and working memory deficits in friedreich ataxia.
AB  - Sustained volitional attention and working memory capacity was examined for the
      first time in people with Friedreich ataxia (FRDA). We administered subtests of
      the Test of Everyday Attention to 16 individuals with molecularly confirmed FRDA
      and gender-, age-, and IQ-matched controls. Clinically significant impairment in
      working memory and sustained volitional attention was evident. Working memory
      deficits correlated significantly with GAA repeat number on the shorter allele of
      the FXN gene, and separately, with disease severity, as measured by the
      Friedreich Ataxia Rating Scale score. Sustained volitional attention was not
      correlated with disease parameters, suggesting that this impairment may not be
      related to the disease process in a simple way. The deficits observed may be the
      result of disruption to corticocerebellar pathways, or directly related to the
      cortical and/or cerebellar pathology evident in people with FRDA.

PMID- 21083966
TI  - Onset and rate of cognitive change before dementia diagnosis: findings from two
      Swedish population-based longitudinal studies.
AB  - We used data from two population-based longitudinal studies to estimate time of
      onset and rate of accelerated decline across cognitive domains before dementia
      diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non
      cases) initially assessed at age 70 with 12 follow-ups over 30 years. The
      Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562
      non-cases), with an average age of 82 years at initial assessment, and 4 follow
      ups spanning 13 years. We fit mixed linear models to the data and determined
      placement of change points by a profile likelihood method. Results demonstrated
      onset of accelerated decline for fluid (speed, memory) versus crystallized
      (verbal, clock reading) abilities occurring approximately 10 and 5 years before
      diagnosis, respectively. Although decline before change points was greater for
      fluid abilities, acceleration was more pronounced for crystallized abilities
      after the change points. This suggests that onset and rate of acceleration vary
      systematically along the fluid-crystallized ability continuum. There is early
      onset in fluid abilities, but these changes are difficult to detect due to
      substantial age-related decline. Onset occurred later and acceleration was
      greater in crystallized abilities, suggesting that those markers may provide more
      valid identification of cases in later stages of the prodromal phase.

PMID- 21083967
TI  - Neuropsychological performance in mainland china: the effect of urban/rural
      residence and self-reported daily academic skill use.
AB  - Age, education, and gender are the most common covariates used to define
      normative standards against which neuropsychological (NP) performance is
      interpreted, but influences of other demographic factors have begun to be
      appreciated. In developing nations, urban versus rural residence may
      differentially affect numerous factors that could influence cognitive test
      performances, including quality of both formal and informal educational
      experiences and employment opportunities. Such disparities may necessitate
      corrections for urban/rural (U/R) status in NP norms. Prior investigations of the
      U/R effect on NP performance typically have been confounded by differences in
      educational attainment. We addressed in this by comparing the NP performance of
      large, Chinese urban (Yunnan Province, n = 201) and rural (Anhui Province, n =
      141) cohorts of healthy adults, while controlling for other demographic
      differences. Although the groups did not differ in global NP scores, a more
      complex pattern was observed within specific NP ability domains and tests. Urban
      participants showed better performance in select measures of processing speed and
      executive functions, verbal fluency, and verbal learning. Self-reported daily use
      of academic skills was predictive of many U/R differences. Controlling for
      academic skill use abrogated most U/R differences but revealed rural advantages
      in select measures of visual reasoning and motor dexterity.

PMID- 21083968
TI  - Banning front-of-package food labels: first Amendment constraints on public
      health policy.
AB  - In recent months, the FDA has begun a crackdown on misleading nutrition and
      health claims on the front of food packages by issuing warning letters to
      manufacturers and promising to develop stricter regulatory standards. Leading
      nutrition policy experts Marion Nestle and David Ludwig have called for an even
      tougher approach: a ban on all nutrition and health claims on the front of food
      packages. Nestle and Ludwig argue that most of these claims are scientifically
      unsound and misleading to consumers and that eliminating them would 'aid
      educational efforts to encourage the public to eat whole or minimally processed
      foods and to read the ingredients list on processed foods'. Nestle and Ludwig are
      right to raise concerns about consumer protection and public health when it comes
      to front-of-package food labels, but an outright ban on front-of-package
      nutrition and health claims would violate the First Amendment. As nutrition
      policy experts develop efforts to regulate front-of-package nutrition and health
      claims, they should be mindful of First Amendment constraints on government
      regulation of commercial speech.

PMID- 21083969
TI  - Developing a database of vitamin and mineral supplements (ViMiS) for the Norfolk
      arm of the European Prospective Investigation into Cancer (EPIC-Norfolk).
AB  - OBJECTIVE: Supplements are an important source of micronutrient intake, which,
      unless taken into account, can misclassify individuals with regard to levels of
      nutrient exposure. A label-based vitamin and mineral supplements (ViMiS) database
      was developed to contain manufacturers' information and to enter supplement use
      by participants in the European Prospective Investigation into Cancer and
      Nutrition in Norfolk (EPIC-Norfolk). The ViMiS database contains information on
      all ingredients, broken down into nutrient information in order to be combined
      with nutrient intake derived from food consumption. DESIGN: Development of the
      ViMiS database and cross-sectional analysis of supplement use in a population
      based study. SETTING: Men and women aged 40-79 years from the general population
      participating in the EPIC-Norfolk study between 1993 and 1997, with data
      available from 7 d diet diaries (7dDD). SUBJECTS: A subset of 19 330 participants
      with available 7dDD and known supplement status. RESULTS: To date, the ViMiS
      database includes 2066 supplements, which altogether contain 16 586 ingredients,
      with a median of eleven nutrient/ingredients per supplement. Forty per cent of
      the cohort took a supplement, of which cod liver oil was the most common (24.5
      %). CONCLUSIONS: The ViMiS database provides a flexible tool for estimating total
      nutrient intake. The high prevalence of supplement use in the general population
      indicates that supplement use needs to be taken into account when examining the
      relationship of intake of particular nutrients to health outcomes.

PMID- 21083970
TI  - Planning a graduate programme in public health nutrition for experienced
      nutrition professionals.
AB  - OBJECTIVE: Public health renewal in Canada has highlighted the need for
      development and expansion of the public health nutrition workforce, particularly
      in northern and rural communities. The purpose of the present paper is to
      describe the planning of a more accessible graduate programme for experienced
      nutrition professionals. The planning effort was challenged by a short timeframe
      between programme approval and implementation and required intense collaboration
      with stakeholders and students. DESIGN: The programme planning model developed by
      The Health Communication Unit (THCU) at the Centre for Health Promotion was used
      to guide the process. This six-step model was familiar to key stakeholders and
      involved pre-planning, conducting a situational assessment, establishing goals
      and objectives, developing strategies and outcome indicators, and monitoring
      feedback. RESULTS: Resource constraints, short timelines and debates around
      distance education options presented challenges that were overcome by conducting
      a thorough needs assessment, creating an advisory committee, engaging key
      stakeholders in the planning process, and building on existing resources.
      Extensive involvement of the first cohort of students in ongoing planning and
      evaluation was particularly helpful in informing the evolution of the programme.
      CONCLUSIONS: The THCU planning model provided a useful framework for stakeholder
      collaboration and for planning and implementing the new graduate programme in
      public health nutrition. Preliminary data suggest that graduates are benefiting
      from their educational experiences through career enhancement opportunities. The
      evaluation strategies built into the programme design will be useful in informing
      ongoing programme development.

PMID- 21083971
TI  - Childhood underweight, weight gain during childhood to adolescence/young
      adulthood and incidence of adult metabolic syndrome in the SUN (Seguimiento
      Universidad de Navarra) Project.
AB  - OBJECTIVE: To assess associations between childhood body weight, weight gain
      during childhood to adolescence/young adulthood and incidence of adult metabolic
      syndrome (MetS). DESIGN: A dynamic prospective cohort study (the SUN Project;
      Seguimiento Universidad de Navarra). Participants were asked to select which of
      nine body images most closely represented their body shape at ages 5 and 20
      years, and it was used as a proxy of BMI. An incident case of MetS was diagnosed
      according to criteria of the International Diabetes Federation. Associations
      between childhood body weight, weight gain during childhood to adolescence/young
      adulthood and incidence of adult MetS were estimated by multiple-adjusted odds
      ratios and their 95 % confidence intervals. SETTING: University of Navarra,
      Spain. SUBJECTS: The study included 5317 university graduates, followed-up for a
      median of 6.1 years. RESULTS: The incidence of MetS was 2.9 % (1.7 % in women and
      5.1 % in men). Among men, body shape at age 5 years was inversely related to
      adult MetS (OR = 0.83, 95 % CI 0.72, 0.97), whereas weight gain during childhood
      to adolescence/young adulthood was directly associated with adult MetS (OR =
      1.49, 95 % CI 1.01, 2.18); both childhood underweight (OR = 5.20, 95 % CI 1.87,
      14.50) and childhood obesity (OR = 4.66, 95 % CI 1.40, 15.51) increased the
      likelihood of adult MetS. No association was apparent among women. CONCLUSIONS:
      These results support treating childhood underweight and weight gain during
      childhood to adolescence/young adulthood as part of comprehensive adult MetS
      prevention efforts in men.

PMID- 21083974
TI  - Preparation and characterization of TAM-loaded HPMC/PAN composite fibers for
      improving drug-release profiles.
AB  - The present paper reports the preparation and characterization of composite
      hydroxypropyl methylcellulose/polyacrylonitrile (HPMC/PAN)-medicated fibers via a
      wet spinning technique. Tamoxifen (TAM) was selected as a model drug. Numerous
      analyses were conducted to characterize the mechanical, structure and morphology
      properties of the composite fibers. The drug content and in vitro dissolution
      behavior were also investigated. SEM images showed that the TAM-loaded HPMC/PAN
      composite fibers had a finger-like outer skin and a porous structure. FT-IR
      spectra demonstrated that there was a good compatibility between polymer and
      drug. Results from X-ray diffraction and DSC suggested that most of the
      incorporated TAM was evenly distributed in the fiber matrix in an amorphous
      state, except for a minority that aggregated on the surface of fibers. The drug
      content in the fibers was lower than that in the spinning solution and about 10%
      of TAM was lost during spinning process. In vitro dissolution results indicated
      that, compared to TAM-PAN fibers, HPMC/PAN composite systems had weaker initial
      burst release effects and more drug-loading. The combination of hydrophilic
      polymer HPMC with PAN could improve the performance of polymer matrix composite
      fibers in regulating the drug-release profiles.

PMID- 21083975
TI  - Genipin-cross-linked electrospun collagen fibers.
AB  - The fabrication of a fibrous collagen scaffold using electrospinning is desirable
      for tissue-engineering applications. Previously, electrospun collagen fibers were
      shown to be unstable in aqueous environments and, therefore, cross-linking is
      essential to stabilize these fibers. In this study genipin, a significantly less
      cytotoxic cross-linking agent compared to glutaraldehyde, was used to cross-link
      electrospun collagen fibers. The significance of this research lies in the use of
      four alcohol/water solvent systems to carry out the crosslinking reaction to
      maintain fibrous morphology during cross-linking. The four cross-linking
      conditions established were: (1) ethanol, 5% water and 3 days, (2) ethanol, 3%
      water and 5 days, (3) ethanol, 5% water and 5 days, and (4) isopropanol, 5% water
      and 5 days at a genipin concentration of 0.03 M. Results illustrated that genipin
      cross-linking was effective in maintaining collagen fiber integrity in aqueous
      and cell culture media environments for up to 7 days. In addition, it was shown
      that fiber swelling could be controlled by using different cross-linking
      conditions. Swelling of cross-linked fibers immersed in Dulbecco's modified eagle
      medium for 7 days ranged from 0 to 59 +/- 4%. The cross-linked fibers were
      analyzed using scanning electron microscopy, Fourier transform infrared
      spectroscopy and ninhydrin assay. Finally, studies using primary human
      fibroblasts indicated good cell adhesion to these scaffolds. Overall, our data
      suggest that these stabilized fibrous collagen scaffolds provide a promising
      environment for tissue-regeneration applications. 

PMID- 21083976
TI  - [A 10-year review of childhood type 1 diabetes mellitus and the clinical value of
      interleukin-10 in diabetic ketoacidosis].
AB  - OBJECTIVE: To review the incident status of childhood type 1 diabetes mellitus
      hospitalized in the Children's Hospital of Zhejiang University School of Medicine
      from 1999 to 2009 and to explore the clinical value of IL-10 in diabetic
      ketoacidosis. METHODS: The clinical data of 263 children with type 1 diabetes
      mellitus hospitalized in the Children's Hospital of Zhejiang University School of
      Medicine from January 1999 to February 2009 were retrospectively reviewed. Serum
      lipid levels were measured in 48 children with type 1 diabetes mellitus and in 24
      healthy children. The diabetic children were classified into two subgroups, with
      or without ketoacidosis. Serum lipid and cytokines levels were compared. RESULTS:
      Childhood type 1 diabetes mellitus was common in females (56.3%). The peak
      incident age of the disease was between 6 and 11.9 years. Diabetic ketoacidosis
      was as the presenting symptom for the first visit in 86 cases (32.7%). The levels
      of serum lipid, blood glucose and HbA1c in diabetic children with ketoacidosis
      were significantly higher than those without ketoacidosis (P<0.05). Logistic
      analysis demonstrated that the increased levels of blood glucose, serum lipid and
      HbA1c were risk factors for diabetic ketoacidosis. The level of serum IL-10 in
      diabetic children with ketoacidosis was significantly higher than that in
      patients without ketoacidosis (P<0.01), while there were no differences in serum
      levels IL-2, IL4, IL-6, TNF-alpha and IFN-gamma between them. Serum levels IL-2,
      IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma in diabetic children were
      significantly higher than those in healthy children (P<0.01). CONCLUSIONS:
      Ketoacidosis is a common acute complication of type 1 diabetes mellitus. The
      disorders of glucose and lipid metabolism are the risk factors for ketoacidosis
      in diabetic children. IL-10 may be a sensitive index of diabetic ketoacidosis in
      children with type 1 diabetes mellitus.

PMID- 21083977
TI  - [Levels of cytokines in peripheral blood of premature infants with chronic lung
      disease].
AB  - OBJECTIVE: This study examined the levels of interleukin (IL)-1beta, IL-6, IL-8
      and tumor necrosis factor alpha (TNF-alpha) in peripheral blood of premature
      infants with chronic lung disease (CLD) in order to investigate the possible role
      of immunologic factors in CLD. METHODS: Twenty-six premature infants who had been
      admitted to the neonatal intensive care unit for 28 days were classified into CLD
      (n=14) and non-CLD (control, n=12) groups. IL-1beta, IL-6, IL-8 and TNF-alpha
      concentrations in peripheral blood were measured by multiplex technique (Bio
      plex). RESULTS: There were no significant differences in peripheral blood levels
      of IL-1beta, IL-6, IL-8 and TNF-alpha between the two groups. CONCLUSIONS: There
      are no significant changes in peripheral blood levels of IL-1beta, IL-6, IL-8 and
      TNF-alpha in premature infants with CLD on the non-acute phase. Immunologic
      factors might not play a key role in CLD on the phase.

PMID- 21083978
TI  - [Ambroxol for the prevention of respiratory distress syndrome in preterm infants:
      a meta analysis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of ambroxol in the prevention of
      respiratory distress syndrome (RDS) in preterm infants. METHODS: Electronic
      searches were performed in the Cochrane Library, PubMED, EMBASE, Chinese CBM,
      Chinese VIP Database, Chinese Wanfang Database and Chinese CNKI Database up to
      the year of 2009 for randomized controlled trials (RCT) on ambroxol for the
      prevention of RDS in preterm infants. The meeting articles related to the RCT
      were manually searched in Pediatrics and Pediatric Research. Meta analysis was
      performed for the results of homogeneous studies by the Cochrane Collaboration's
      software RevMan 5.0.17. RESULTS: Six RCTs involving 823 preterm infants were
      included, and the quality assessment for the trials demonstrated 1 article as A
      class, 1 article as B class and 4 articles as C class. The Meta analysis showed
      that ambroxol administration significantly reduced the incidence of RDS (OR=0.24,
      95%CI: 0.15 - 0.64, P<0.01), bronchopulmonary dysplasis (BPD, OR=0.41, 95%CI:
      0.23 - 0.75, P<0.01), intraventricular hemorrhage (IVH, OR=0.39, 95%CI:0.24 -
      0.64, P<0.01), patent ductus arteriosus (PDA, OR=0.33, 95%CI: 0.17 - 0.67,
      P<0.01) and pulmonary infection (OR=0.24, 95%CI:0.14 - 0.38, P<0.01). No adverse
      events related to the ambroxol treatment were reported. CONCLUSIONS: The current
      evidence shows that early use of ambroxol can reduce the risk of RDS, BPD, IVH,
      PDA and pulmonary infection in preterm infants.

PMID- 21083979
TI  - [Relationship between serum estradiol levels in the early postnatal period and
      the occurrence of hyaline membrane disease and bronchopulmonary dysplasia in
      neonates].
AB  - OBJECTIVE: This study examined the changes of serum levels of estradiol during
      the early postnatal period in neonates in order to investigate the possible
      relationship between the serum estradiol levels and the occurrence of pulmonary
      hyaline membrane disease (HMD) and bronchopulmonary dysplasia (BPD). METHODS:
      Fifty-nine premature infants with the gestational age between 26 and 32 weeks and
      61 full-term infants with the gestational ages between 37 and 42 weeks were
      enrolled. Serum levels of estradiol were measured on postnatal days 1, 3 and 7.
      RESULTS: Serum levels of estradiol decreased rapidly after birth in both
      premature and term infants and there were significant differences among different
      postnatal ages groups. However, there were no significant differences in the
      serum estradiol levels between the premature and term groups on postnatal days 1,
      3 and 7. Serum estradiol levels measured in premature infants with HMD were not
      statistically different from those in premature infants without HMD on all time
      points. Serum estradiol levels in premature infants with BPD were higher than
      those in premature infants without BPD on postnatal day 3, but there were no
      noticeable differences on postnatal days 1 and 7. CONCLUSIONS: Serum estradiol
      levels decline rapidly within 7 days after birth in both premature and term
      infants. Serum estradiol levels in the early postnatal period are not associated
      with the occurrence of HMD and BPD, suggesting that serum estradiol in the early
      postnatal period can not be used as a marker for predicting the development of
      HMD and BPD.

PMID- 21083980
TI  - [Influencing factors of umbilical cord separation in full-term newborns].
AB  - OBJECTIVE: To investigate the influencing factors for the time of umbilical cord
      separation in full-term newborns. METHODS: The time of umbilical cord separation
      was recorded in 337 full-term newborns. Single factor and multifactor
      unconditioned logistic regression were performed to investigate the influencing
      factors of umbilical cord separation. Fourteen possible factors associated with
      the time of umbilical cord separation, including sex, gestational age, body
      weight, position of umbilical cord ligature, length of umbilical cord stump,
      umbilical cord diameter, cleanness of umbilical cord paster, hand cleanness of
      medical staff and family members and umbilical infection, were involved. RESULTS:
      The single factor correlative analysis demonstrated that the position of
      umbilical cord ligature, length of umbilical cord stump, umbilical cord diameter,
      cleanness of umbilical cord paster, and umbilical infection were influencing
      factors for the time of umbilical cord separation (P<0.05). The multifactor
      unconditioned logistic regression analysis demonstrated four major influencing
      factors for umbilical cord separation: position of umbilical cord ligature,
      length of umbilical cord stump, cleanness of umbilical cord paster, and umbilical
      infection. CONCLUSIONS: The following factors contribute to early separation of
      umbilical cord: the proper position of umbilical cord ligature (<0.5 cm to
      umbilical ring), the umbilical cord stump of <0.5 cm, keeping the umbilical cord
      paster clean and the prevention of umbilical infection.

PMID- 21083981
TI  - [Correlation of hypoproteinemia with C-reactive protein and procalcitonin in
      children with sepsis].
AB  - OBJECTIVE: To investigate the correlation of hypoproteinemia with inflammation
      parameters C-reactive protein (CRP), procalcitonin (PCT) and WBC in children with
      sepsis. METHODS: Seventy-three children with sepsis (including 22 severe sepsis)
      and 40 non-sepsis children (control group) were enrolled. Serum albumin levels
      were measured on admission. Based on the level of serum albumin, 73 cases of
      sepsis were classified into three groups: mild hypoproteinemia, severe
      hypoproteinemia and normal albumin. Blood CRP, PCT and WBC levels were compared
      in the three groups. The correlation of CRP, PCT and WBC with serum albumin level
      was evaluated. RESULTS: Serum albumin levels in the sepsis groups (severe or non
      severe) were significantly lower than those in the control group (P<0.05), and
      the severe sepsis group showed more decreased albumin levels compared with the
      non-severe sepsis group (P<0.05). Blood CRP, PCT and WBC levels in the mild
      hypoproteinemia group were higher than those in the normal albumin group
      (P<0.05), and the severe hypoproteinemia group showed more increased blood CRP,
      PCT and WBC levels compared with the mild hypoproteinemia group (P<0.05). The
      incidence of multiple organ failure in the severe hypoproteinemia group was
      significantly higher than that in the normal albumin group (P<0.05). Serum
      albumin levels were negatively correlated with blood CRP, PCT and WBC levels.
      CONCLUSIONS: Serum albumin levels decrease in children with sepsis, and the more
      serious the illness, the lower serum albumin levels, resulting in a worse
      prognosis. CRP, PCT and WBC are negatively correlated to serum albumin levels in
      children with sepsis.

PMID- 21083982
TI  - [Efficacy of highly active antiretroviral therapy for childhood acquired
      immunodeficiency syndrome].
AB  - OBJECTIVE: To investigate the efficacy of highly active antiretroviral therapy
      (HAART) for acquired immunodeficiency syndrome (AIDS) in children. METHODS: The
      clinical data of 38 children (2-15 years old) with AIDS from a region of Rwanda
      and who had received HAART were retrospectively reviewed. RESULTS: All of 13
      children with anemia showed improved anemia symptoms after HAART. The hemoglobin
      contents returned to normal levels in 12 children with mild or moderate anemia.
      CD4 T lymphocytes increased by 24%-1 181% in 5 out of 6 cases with severe
      immunodeficiency after HAART. During the HAART, the weight gain averaged 2.3 kg
      yearly. The growth and development in 5 out of 8 children with delayed growth
      restored the levels of normal children of the same age after HAART. CONCLUSIONS:
      HAART can improve the health status in children with AIDS and is effective for
      childhood AIDS.

PMID- 21083983
TI  - [Expression of Rock2 and TGF-beta1 mRNA and glucocorticoid intervention in
      asthmatic rats].
AB  - OBJECTIVE: To study the roles of rhoassociated coiled coil forming protein kinase
      2 (Rock2) and transforming growth factor-beta1 (TGF-beta1) mRNA in acute asthma
      and the effect of glucocorticoid intervention on the Rock2 and TGF-beta1 mRNA
      expression in rats. METHODS: Forty-eight male rats were randomly divided into 4
      groups (n=12 each): asthma, control, dexamethasone treated (DXM) and budesonide
      treated (BUD). Rat model of asthma was prepared by the ovalbumin (OVA) challenge.
      The animals were sacrificed 24 hrs after the last challenge. The total cell
      number and differentiation cell number were counted in bronchoalveolar lavage
      fluid (BALF). The protein expression of Rock2 was ascertained by
      immunohistochemistry and the mRNA expression of TGF-beta1 was ascertained by
      hybridization in situ. RESULTS: The pathological changes in the BUD and the DXM
      groups were alleviated when compared with the asthma group. The total cell number
      and the percentage of eosinophil (EOS), polymorphonuclear leukocytes (PMN) and
      lymphocytes (Lym) in BALF in the asthma group were significantly higher than
      those in the control group (P<0.01). The percentage of macrophage (Mf) in the
      asthma group was significantly lower than that in the control group (P<0.01). The
      total cell number and the percentage of EOS and Lym in BALF in the DXM and the
      BUD groups decreased, while the percentage of Mf increased significantly compared
      with those in the asthma group (P<0.01). The Rock2 and TGF-beta1 mRNA expression
      in lung tissues in the asthma group increased significantly compared with those
      in the control, BUD and DXM groups, while there were no significant differences
      in the Rock2 expression and TGF-beta1 mRNA expression between the DXM or BUD
      group and the control group. CONCLUSIONS: The expression of Rock2 and TGF-beta1
      mRNA in lung tissues is increased in rats with acute asthma. Glucocorticoids can
      significantly decrease the expression of Rock2 and TGF-beta1 in lung tissues,
      thus alleviates airway inflammation.

PMID- 21083984
TI  - [Effects of endogenous carbon monoxide on gene expression profiles associated
      with the apoptosis of pulmonary arterial smooth muscle cells].
AB  - OBJECTIVE: To identify the gene expression profiles associated with the apoptosis
      of pulmonary arterial smooth muscle cells stimulated by carbon monoxide (CO).
      METHODS: Primary cultured Sprague-Dawley rat pulmonary arterial smooth muscle
      cells (PASMC) were stimulated by platelet-derived growth factor (PDGF, 20 ng/mL)
      and hemin (20 MUmol/L). Cells were harvested after 2 hrs and Affymetrix
      microarrays were used to detect the gene expression profile. RESULTS: Some genes
      associated with Map2k3 (P38) signal pathway, such as CyclinD1, CyclinH, CyclinL1,
      MAP2K3, Kras and Nras, were upregulated, but P27 expression was downregulated
      after PDGF treatment. After endogenous CO treatment, some genes associated with
      P53 pathway, such as Gadd45alpha, P21 and Trp53inp1, were upregulated.
      CONCLUSIONS: P53 pathway probably plays an important role in apoptosis of
      pulmonary arterial smooth muscle cells treated with endogenous CO.

PMID- 21083985
TI  - [Effect of spleen tyrosine kinase on the proliferation of pulmonary vascular
      smooth muscle cells in rats].
AB  - OBJECTIVE: To investigate the role of spleen tyrosine kinase (Syk) in rat
      pulmonary vascular smooth muscle cells (PVSMCs) proliferation induced by platelet
      derived growth factor-BB (PDGF-BB). METHODS: PVSMCs from male Sprague-Dawley rats
      were cultured in vitro and the cells of passages 3-5 were used in the experiment.
      PVSMCs were stimulated by PDGF-BB and were treated with three different doses of
      piceatannol, a Syk selective inhibitor. Cell proliferation was assessed by methyl
      thiazolyl tetrazolium (MTT) assay. DNA synthesis was measured by 3H-thymidine
      incorporation (3H-TdR). Cellular cycle was observed by flow cytometry. Syk mRNA
      and protein expression were detected using real-time quantitative PCR and Western
      blot, respectively. RESULTS: The expression of Syk protein of PVSMCs was
      significantly up-regulated following PDGF-BB stimulation. PDGF-BB stimulation
      dramatically increased PVSMCs proliferation. After piceatannol treatment, both
      Syk mRNA and protein expression decreased and the proliferation of PVSMCs was
      inhibited in a dose-dependent manner. CONCLUSIONS: Syk may promote PVSMCs
      proliferation induced by PDGF-BB.

PMID- 21083987
TI  - [Effects of bone marrow stromal cells and VLA-4 antibody on apoptosis of
      childhood leukemia cells].
AB  - OBJECTIVE: To study the protective effect of bone marrow stromal cells (BMSCs)
      upon childhood leukemia cells and the influence of VLA-4 antibody in vitro on
      leukemia cell apoptosis. METHODS: BMSCs from children with acute leukemia-were
      isolated by human lymphocyte separation medium. BMSCs (adherent) and leukemia
      cells (suspended) were cultured in vitro. This study included four groups:
      leukemia cells alone (control), leukemia cells+BMSCs, leukemia cells+BMSCs
      supernatant and leukemia cells+BMSCs+VLA-4 antibody. The apoptosis rate of
      leukemia cells in the four groups was determined by Annexin V-FITC double-labeled
      flow cytometry. The expression of survivin and bcl-2 genes in leukemia cells was
      ascertained by RT-PCR. RESULTS: The apoptosis rate of leukemia cells in the
      leukemia cells+BMSCs and the leukemia cells+BMSCs supernatant groups was lower
      than that in the control group (P<0.05). Compared with the leukemia cells+BMSCs
      and the leukemia cells+BMSCs supernatant groups, the apoptosis rate of leukemia
      cells in the VLA-4 antibody group increased significantly (P<0.05). In the VLA-4
      antibody group, the apoptosis rate of leukemia cells increased with prolonged
      culture time. There were significant differences in the apoptosis rate between 12
      hrs and 24 hrs after VLA-4 antibody treatment (P<0.01). The expression of
      survivin and bcl-2 genes in leukemia cells from the VLA-4 antibody groups was
      reduced compared with that from the leukemia cells+BMSCs and the leukemia
      cells+BMSCs supernatant groups (P<0.05). CONCLUSIONS: BMSCs play protective roles
      on leukemia cells. VLA-4 antibody can block the adhesion between BMSCs and
      leukemia cells and promote leukemia cell apoptosis.

PMID- 21083986
TI  - [Effects of antenatal administration of dexamethasone and betamethasone on signal
      transduction of bone morphogenetic protein in the fetal lungs of rats].
AB  - OBJECTIVE: To study the role of antenatal glucocorticoid (dexamethasone and
      betamethasone) on bone morphogenetic protein (BMP) signal transduction of the rat
      fetal lungs. METHODS: Fifteen pregnant rats were randomly divided into five
      groups: the rats treated with dexamethasone for 1 day (1D-DEX) or 3 days (3D
      DEX), with betamethasone for 1 day (1D-BEX) or 3 days (3D-BEX) or with normal
      saline (control group), followed cesarean section on the 19th day of gestation.
      The mRNA levels of BMP4, BMPR-II, Smad1 and ATF-2 of fetal rat lungs were
      ascertained by reverse transcriptase polymerase chain reaction (RT-PCR). The
      expression of BMP4, BMPR-II, Smad1 and ATF-2 antigen expression in fetal lungs
      was assessed by immune histochemical staining. The expression of BMP4 and BMPR-II
      was determined by Western blot. RESULTS: The levels of BMP4, BMPR-II and Smad1
      mRNA expression were up-regulated in the 1D-BEX, 3D-BEX and 3D-DEX groups
      compared with those in the control group (P<0.05). The immune histochemiscal
      analysis showed that the expression of BMP4, BMPR-II, Phospho-Smad1 (pSmad1) and
      ATF-2 in the 1D-BEX, 3D-BEX and 3D-DEX groups was significantly higher than that
      in the control group (P<0.01). The results of Western blot demonstrated that the
      expression of BMP4 and BMPR-II protein increased significantly in the 1D-BEX, 3D
      BEX and 3D-DEX groups when compared with the control group (P<0.01). CONCLUSIONS:
      Betamethasone and dexamethasone may play important roles in the regulation of BMP
      signal transduction in the rat fetal lungs. Up-regulation of BMP4, BMPR-II and
      Smad1 might be one of crucial factors for the glucocorticoid-induced maturity of
      fetal lungs.

PMID- 21083988
TI  - [Role of caspase-8 in TRAIL-induced apoptosis of neuroblastoma cell lines].
AB  - OBJECTIVE: The aim of this study was to investigate whether the induction of
      caspase-8 by gamma-interferon (IFNgamma) renders neuroblastoma (NB) cells
      sensitive to tumor necrosis factor related apoptosis inducing ligand(TRAIL).
      METHODS: Caspase-8 mRNA expression was determined by RT-PCR. The effects of
      IFNgamma, TRAIL, IFNgamma +TRAIL and caspase-8 inhibitor+ TRAIL on the growth and
      apoptosis of NB cells were detected with the methods of reduction rate of Alamar
      Blue assay and flow cytometry. The relative caspase-8 activity was measured with
      colorimetric assay. RESULTS: Caspase-8 expression was detectable in CHP212 cells
      which were sensitive to TRAIL, with an increased expression after treatment with
      IFNgamma. Caspase-8 was undetectable in SH-SY5Y(SY5Y) cells which were resistant
      to TRAIL, but an increased expression of caspase-8 mRNA was found after treatment
      with IFNgamma. Moreover, TRAIL combined with IFNgamma induced apoptosis in SY5Y
      cells. The relative caspase-8 activity of CHP212 cells increased with the
      prolonged TRAIL action time. The relative caspase-8 activity of SY5Y cells in the
      IFNgamma+TRAIL group was significantly higher than those of the control,
      IFNgamma, TRAIL and inhibitor groups. CONCLUSIONS: NB cells expressing caspase-8
      are sensitive to TRAIL. TRAIL induces apoptosis in NB cells with an increase of
      relative caspase-8 activity.

PMID- 21083989
TI  - [Effect of astrocytes with different degrees of proliferation on multidrug
      resistance gene expression in rats with epilepsy].
AB  - OBJECTIVE: To study the relationship of activated astrocytes and multidrug
      resistance gene (MDR) expression in rats with epilepsy. METHODS: Astrocytes of
      neonatal Sprague-Dawley rats were separated and cultured. The cultured cells of
      passage 3 were activated by TNF-alpha for 2, 24 or 48 hrs. The culture media of
      cells with different degrees of proliferation were infused to the lateral
      cerebral ventricle of rats with epilepsy. The expression of MDR in the brain
      tissue was ascertained by PCR, immunocytochemistry and Western blot. RESULTS:
      After 2 hrs of TNF-alpha stimulation, astrocytes began to proliferate, and
      reached a peak at 24 hrs. The expression of MDR in the brain tissue increased
      after infusion of culture medium of proliferated astrocytes in the TNF
      stimulation group compared with that in the control group without TNF
      stimulation. The level of MDR expression in the TNF stimulation group was
      positively correlated with the degrees of cell proliferation. CONCLUSIONS:
      Proliferation of astrocytes can increase the expression of MDR in rats with
      epilepsy and is probably involved in the development of refractory epilepsy.

PMID- 21083991
TI  - [Anorectal motility in children with functional constipation].

PMID- 21083990
TI  - [Expression of interleukin-6 in rat model of doxorubicin-induced nephropathy].
AB  - OBJECTIVE: The pathogenesis of minimal change nephrotic syndrome (MCNS) remains
      unclear. This study aimed to investigate the expression of interleukin-6 (IL-6)
      in rats with doxorubicin-induced nephropathy and its possible roles in the
      pathogenesis of MCNS. METHODS: Eighty-three male Wistar rats were randomly
      assigned into a control group (n=32) and a nephropathy group (n=51). Nephropathy
      was induced by a single tail vein injection of doxorubicin (5 mg/kg). The control
      group was injected with normal saline. Twenty-four-hour urinary protein excretion
      was measured 7, 14, 28 and 42 days after doxorubicin injection. IL-6 expression
      in urine and renal tissues was determined using ELISA 7, 14, 28 and 42 days after
      doxorubicin injection. RESULTS: The urinary protein excretion increased
      significantly in the nephropathy group 7, 14, 28 and 42 days after doxorubicin
      injection compared with that in the control group (P<0.01). IL-6 expression in
      urine and renal tissues increased significantly 7, 14, 28 and 42 days after
      doxorubicin injection compared with that in the control group (P<0.01). IL-6
      expression in urine and renal tissues was positively correlated with 24-hour
      urinary protein excretion in the nephropathy group (r=0.794, P<0.01; r= 0.870,
      P<0.01). IL-6 expression in urine was positively correlated with that in renal
      tissues (r=0.739, P<0.01). CONCLUSIONS: IL-6 expression in the urine and renal
      tissues is increased in MCNS rats. IL-6 might play an important role in the
      pathogenesis of MCNS.

PMID- 21083992
TI  - [Application of susceptibility weighted imaging in brain injuries of preterm
      infants].

PMID- 21083993
TI  - [Serum NT-proBNP levels in neonates with severe asphyxia and the effects of
      nalmefene on the NT-proBNP levels].

PMID- 21083995
TI  - [Infantile cortical hyperostosis: report of two cases].

PMID- 21083994
TI  - [Prune Belly syndrome complicated by pectus excavatum, spleen and left kidney
      congenital absence and situs inversus viscerum: a case report].

PMID- 21083996
TI  - [Disseminated histoplasmosis in a boy presenting fever and jaundice as first
      manifestations].

PMID- 21083997
TI  - [Type 1 diabetes mellitus in both a boy and his younger sister].

PMID- 21083998
TI  - [Role of reactive oxygen species in persistent pulmonary hypertension of the
      newborn].

PMID- 21083999
TI  - Cost-effectiveness of screening high-risk HIV-positive men who have sex with men
      (MSM) and HIV-positive women for anal cancer.
AB  - BACKGROUND: Anal cancer is uncommon and predominantly a disease of the elderly.
      The human papillomavirus (HPV) has been implicated as a causal agent, and HPV
      infection is usually transmitted sexually. Individuals who are human
      immunodeficiency virus (HIV)-positive are particularly vulnerable to HPV
      infections, and increasing numbers from this population present with anal cancer.
      OBJECTIVE: To estimate the cost-effectiveness of screening for anal cancer in the
      high-risk HIV-positive population [in particular, men who have sex with men
      (MSM), who have been identified as being at greater risk of the disease] by
      developing a model that incorporates the national screening guidelines criteria.
      DATA SOURCES: A comprehensive literature search was undertaken in January 2006
      (updated in November 2006). The following electronic bibliographic databases were
      searched: Applied Social Sciences Index and Abstracts (ASSIA), BIOSIS previews
      (Biological Abstracts), British Nursing Index (BNI), Cumulative Index to Nursing
      and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews
      (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE,
      MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, NHS Database of
      Abstracts of Reviews of Effects (DARE), NHS Health Technology Assessment (HTA)
      Database, PsycINFO, Science Citation Index (SCI), and Social Sciences Citation
      Index (SSCI). STUDY SELECTION: Published literature identified by the search
      strategy was assessed by four reviewers. Papers that met the inclusion criteria
      contained the following: data on population incidence, effectiveness of
      screening, health outcomes or screening and/or treatment costs; defined suitable
      screening technologies; prospectively evaluated tests to detect anal cancer.
      Foreign-language papers were excluded. Searches identified 2102 potential papers;
      1403 were rejected at title and a further 493 at abstract. From 206 papers
      retrieved, 81 met the inclusion criteria. A further treatment paper was added,
      giving a total of 82 papers included. DATA EXTRACTION: Data from included studies
      were extracted into data extraction forms by the clinical effectiveness reviewer.
      To analyse the cost-effectiveness of screening, two decision-analytical models
      were developed and populated. RESULTS: The reference case cost-effectiveness
      model for MSM found that screening for anal cancer is very unlikely to be cost
      effective. The negative aspects of screening included utility decrements
      associated with false-positive results and with treatment for high-grade anal
      intraepithelial neoplasia (HG-AIN). Sensitivity analyses showed that removing
      these utility decrements improved the cost-effectiveness of screening. However,
      combined with higher regression rates from low-grade anal intraepithelial
      neoplasia (LG-AIN), the lowest expected incremental cost-effectiveness ratio
      remained at over 44,000 pounds per quality-adjusted life-year (QALY) gained.
      Probabilistic sensitivity analysis showed that no screening retained over 50%
      probability of cost-effectiveness to a QALY value of 50,000 pounds. The screening
      model for HIV-positive women showed an even lower likelihood of cost
      effectiveness, with the most favourable sensitivity analyses reporting an
      incremental cost per QALY of 88,000 pounds. LIMITATIONS: Limited knowledge is
      available about the epidemiology and natural history of anal cancer, along with a
      paucity of good-quality evidence concerning the effectiveness of screening.
      CONCLUSIONS: Many of the criteria for assessing the need for a screening
      programme were not met and the cost-effectiveness analyses showed little
      likelihood that screening any of the identified high-risk groups would generate
      health improvements at a reasonable cost. Further studies could assess whether
      the screening model has underestimated the impact of anal cancer, the results of
      which may justify an evaluative study of the effects of treatment for HG-AIN.

PMID- 21084001
TI  - Storage of buffy-coat-derived platelets in additive solution: in vitro effects on
      platelets of the air bubbles and foam included in the final unit.
AB  - BACKGROUND: The air bubbles and foam that develop during the preparation of
      platelet units have traditionally been considered to interact with the platelets,
      causing activation and release reactions. However, there actually seems to be no
      data available concerning the platelet damage that may occur as a result of air
      bubbles and foam present in the final unit. In this in vitro study we, therefore,
      investigated the effects of not removing air bubbles/foam from final platelet
      units, by measuring in vitro parameters during a 7-day storage period. DESIGN AND
      METHODS: Platelet samples (n=8) from eight pools of 12 buffy-coats were aliquoted
      and prepared with the OrbiSac system for storage with (test) or without
      (reference) air bubbles/foam included in the final units. The metabolic, cellular
      and activation parameters of all units, comprising approximately 30% plasma and
      70% SSP+ platelet additive solution, were analysed during the 7-day storage
      period. RESULTS: Differences in platelet counts and contents between the test and
      reference units were detected throughout storage (p<0.05 at day 5 and p<0.01 at
      day 7). Lactate dehydrogenase increased during storage in the test units and was
      significantly higher than in the reference units (p<0.01 from day 5). The
      hypotonic shock response was greater in the reference units (p<0.05 on day 2 and
      p<0.01 from day 5). The extent of shape changes was less in the test units
      (p<0.05 until day 5 and p<0.01 on day 7). CD62P was higher in the test units
      (p<0.05 on day 7). CD42b decreased in all units but was lower in the test units
      (p<0.01 on day 5). CD41, CD61 and PAC-1 showed no difference throughout storage
      between the units (p=NS). Aggregates were visible (day 7) and occurred in three
      of the test units. pH was maintained at >6.8 (day 7) and swirling remained at the
      highest level (score =2) for all units throughout storage. CONCLUSIONS: This
      study shows that storage with air bubbles/foam causes considerable enhancement of
      disintegration of platelets. In addition, various in vitro parameters of the
      platelets remaining seem to be negatively affected. The results of this study
      suggest that platelets should be stored without air bubbles/foam, given that
      these cause increased disintegration of platelets.

PMID- 21084002
TI  - Clinical management of paroxysmal nocturnal haemoglobinuria in pregnancy: three
      case reports.

PMID- 21084000
TI  - Risk factors for venous and arterial thrombosis.

PMID- 21084003
TI  - A study of leucocyte removal by the RemoweLL cardiotomy reservoir.
AB  - BACKGROUND: Cerebral damage is a relatively frequent complication of
      cardiopulmonary perfusion. Leucocyte activation and lipid microembolisation are
      among the possible causes. The removal of leucocytes and lipid microparticles
      from the cardiotomy suction blood could prevent this complication. METHODS: We
      studied the properties of a cardiotomy reservoir (RemoweLL, EUROSETS), which
      contains a filtering layer designed to remove some leucocytes and lipid
      microparticles. The reservoir was loaded with red cell concentrates or whole
      blood units, some of them containing hyperlipidaemic plasma. The extent of
      leucocyte and lipid removal was evaluated with reference to the storage age and
      pre-filtration absolute values of the products. RESULTS: On average, the
      cardiotomy reservoir removed 35-39% of total leucocytes, with a slight preference
      for neutrophil granulocytes. This device also retained 26-30% of platelets. The
      efficiency was not influenced by the storage age of the filtered product nor by
      the total cell load, within the explored range (323x10(6) - 1,345 x10(6) total
      leucocytes). Lipid (cholesterol, triglycerides) removal was minimal (about 3-6%).
      DISCUSSION: The RemoweLL device removed more than a third of the leucocytes from
      the processed blood. Lipid removal was minimal but the lipid particles in our
      model (chylomicrons) have a diameter 100-fold smaller than the particles believed
      to be responsible for clinical effects. This device seems promising and worthy of
      further studies to document the saturation point of leucocyte removal. On the
      other hand, lipid removal should be studied in a model more closely resembling
      the clinical situation in which the device is expected to be used.

PMID- 21084004
TI  - Cytometry and Rhesus: not only for haemolytic disease of the newborn.

PMID- 21084006
TI  - Lack of evidence of neoantigen formation in different batches of a double-virus
      inactivated factor VIII concentrate manufactured in Argentina.

PMID- 21084005
TI  - Laboratory characteristics and clinical utility of post-operative cell salvage:
      washed or unwashed blood transfusion?

PMID- 21084007
TI  - The effect of repeated blood donations on the iron status of male Saudi blood
      donors.
AB  - BACKGROUND: Regular blood donation can lead to iron deficiency. Screening donors'
      serum ferritin levels at the time of first donation and subsequently once every
      year is a very rational way to pick up iron deficiency in a voluntary blood donor
      population. The aim of this study was to determine the effect of blood donation
      and the prevalence of erythropoiesis with iron deficiency (sideropenia) in Saudi
      male blood donors. MATERIALS AND METHODS: The study was prospectively conducted,
      between December 2008 and March 2009, on 182 male native Saudi blood donors at
      King Fahd Central Hospital in Jazan region, Saudi Arabia. Each donor gave 450 +/-
      50 mL of whole blood. Following the donation, samples were removed into 2.5 mL
      EDTA tubes for measurement of mean cell volume (MCV) and mean corpuscular
      haemoglobin (MCH) and into 7.5 mL plain tubes for estimation of iron and serum
      ferritin concentrations. The blood donors were divided into five groups,
      according to the number of donations they had given in the preceding 3 years. The
      blood donors in group I were first-time donors, with no previous history of blood
      donation. Group II donors had donated once in the last 3 years. Subjects in
      groups III, IV and V had donated more than once in the preceding 3 years and were
      considered regular donors. RESULTS: The mean serum iron was significantly higher
      among subjects with no previous history of blood donation (group I) than among
      regular donors who had donated twice or more. The difference in serum ferritin
      concentration was statistically significant (p<0.05) when comparing regular
      donors in group III (72.4 MUg/L), group IV (67.4 MUg/L) and group V (26.2 MUg/L)
      with first-time blood donors (131.4 MUg/L). In contrast, the difference in the
      concentration of serum ferritin between subjects in group II (98.9 MUg/L), who
      had donated once in the last 3 years, and in first-time blood donors (131.4
      MUg/L) was not statistically significant (p<0.131). None of the group I donors
      suffered from iron deficiency, whereas 2.8% of the donors who had donated between
      two to five times had iron deficiency. The prevalence of erythropoiesis with iron
      deficiency in regular blood donors was 4.3%. CONCLUSION: The results of this
      study show that an increase in the number of donations results in an increase in
      the frequency of depleted iron stores and subsequently in erythropoiesis with
      iron deficiency, although the level of haemoglobin remained acceptable for blood
      donation. This result may indicate the need to review the guidelines on
      acceptance of donors.

PMID- 21084008
TI  - Antibody elutions in Thai patients with a positive direct antiglobulin test.
AB  - BACKGROUND: The direct antiglobulin test is performed to determine whether an
      anaemic patient with evidence of haemolysis has autoimmune or alloimmune
      haemolytic anaemia. MATERIALS AND METHODS: We determined the antibody specificity
      of eluted IgG antibodies from patients' blood samples with a positive direct
      antiglobulin test. Overall, 134 Thai patients were included in this study. EDTA
      blood samples were obtained from recently transfused patients, patients with
      unexplained anaemia and patients who had serum antibodies detected during routine
      pre-transfusion tests from different hospital blood banks. These complicated
      samples were sent to the National Blood Centre of the Thai Red Cross Society for
      investigation and to find compatible blood components. Each blood sample
      underwent a direct antiglobulin test with the gel technique using polyspecific
      antihuman globulin and mononospecific anti-IgG and anti-C3d. Acid eluates were
      prepared from the samples for which the direct antiglobulin test was positive and
      the specificities of the eluted antibodies were determined by the gel technique.
      RESULTS: Of the samples tested, 101 showed a positive direct antiglobulin test
      result (75.4%) using polyspecific antihuman globulin sera whereas only 95 samples
      (70.9%) were positive with anti-IgG or anti-IgG and anti-C3d. Moreover, 54 of 95
      eluates (56.8%) were positive for antibody screening and tested with the reagent
      panel cells. Twenty-one eluates had specific alloantibodies, which were
      concordant with the findings in the patients' sera and all patients had a history
      of blood transfusion. Additionally, 33 eluates contained pan-agglutinins.
      Interestingly, alloantibodies could be determined using titration studies in 5 of
      26 eluates with pan-agglutinins. CONCLUSION: Although the direct antiglobulin
      test is not routinely performed in pre-transfusion screening, this test and
      elution studies would be useful in patients with a history of previous
      transfusions, and in those for whom compatible blood cannot be found.

PMID- 21084009
TI  - Vitamin K in neonates: facts and myths.

PMID- 21084010
TI  - Adverse reactions in whole blood donors: an Indian scenario.
AB  - BACKGROUND: Whole blood donation is generally considered to be a safe procedure,
      but occasionally adverse reactions of varying severity may occur during or at the
      end of the collection. The aim of the study was to estimate the frequency and
      type of adverse events occurring during blood donation and to assess the
      practices which would help to minimise them. MATERIALS AND METHODS: This
      retrospective single-centre study was conducted from June 2007 to November 2009
      at a regional blood transfusion centre. All whole blood donations made at the
      centre were analysed. All adverse events occurring during or at the end of
      donation were noted using a standardised format. RESULTS: Overall 113 adverse
      events were reported in relation to 19,045 donations, resulting in an overall
      adverse event rate of 0.6%, that is, an incidence of 1 in every 166 donations.
      Presyncopal symptoms, in other words vasovagal reactions of mild intensity, were
      the most commonly observed adverse reactions and accounted for approximately 70%
      of all adverse reactions noted. CONCLUSIONS: Only 0.6% of blood donations were
      complicated by adverse events and most of these events were presyncopal symptoms.
      Our study reinforces the fact that blood donation is a very safe procedure which
      could be made even more event-free by following certain friendly, reassuring and
      tactful practices.

PMID- 21084011
TI  - Hyperferritinaemia without iron overload in a blood donor.

PMID- 21084012
TI  - Autologous transfusion of drain contents in elective primary knee arthroplasty:
      its value and relevance.
AB  - BACKGROUND: Total knee arthroplasty is associated with significant post-operative
      blood loss often necessitating blood transfusions. Blood transfusions may be
      associated with transfusion reactions and may transmit human immunodeficiency
      virus, hepatitis C virus and hepatitis B virus, with devastating consequences.
      After total knee arthroplasty, transfusion of the contents of an autologous drain
      is becoming common practice. The aim of our study was to look at the
      effectiveness of these drains in elective primary total knee arthroplasty.
      MATERIALS AND METHODS: A prospective study was conducted including 70 non
      randomised patients. A normal suction drain was used in 35 patients (group A),
      whereas in the other 35 patients, a CellTransTM drain was used (group B). All the
      operations were performed by four surgeons using a tourniquet with a medial
      parapatellar approach. Pre- and post-operative haemoglobin concentrations were
      recorded in both groups. A Student's t-test was applied to determine the
      statistical significance of the data collected. RESULTS: The average fall in post
      operative haemoglobin was 3.66 g/dL (SD 1.46; range, 0.6-7.0) among patients in
      whom the simple drain was used (group A) and 2.29 g/dL (SD 0.92; range, 0.6-5.9)
      among those in whom the CellTransTM drain was used (group B) (p<0.0001). Twenty
      five units of allogeneic blood were required in group A compared to four units in
      group B. The rate of transfusion was 5.7% (2 patients) in the group in which
      CellTransTM drain was used and 25.7% (9 patients) in the group in which a simple
      suction drain was used. DISCUSSION: Total knee arthroplasty is associated with
      significant post-operative blood loss despite best operative technique.
      Autologous reinfusion of the contents of a CellTransTM drain significantly
      reduces the rate of post-operative blood transfusion. This study indicates that
      the use of an autologous drain could be recommended as routine practice in
      primary total knee arthroplasty.

PMID- 21084013
TI  - Anaemia in elderly patients.

PMID- 21084015
TI  - Consequences of ABO incompatibility in multiple myeloma patients undergoing
      peripheral blood stem cell transplantation after reduced intensity conditioning.
AB  - BACKGROUND: Although the ABO blood group is one of two major antigen systems of
      relevance for transplantation in humans, there are still conflicting data
      concerning the influence of ABO-incompatibility on transplant outcome. This study
      investigated the effect of ABO incompatibility in recipients of haematopoietic
      progenitor cell transplants from related donors after reduced intensity
      conditioning (RIC) regimens. MATERIALS AND METHODS: We retrospectively analysed
      data from 19 multiple myeloma patients included in a prospective RIC allogeneic
      haematopoietic progenitor cell transplantation protocol, focusing on engraftment,
      transfusion requirement, Graft-versus-Host Disease, transplant-related mortality
      and survival. RESULTS: Five out of the 19 patients (26%) received an ABO
      incompatible transplant, with minor ABO-mismatch in two patients (10%), major ABO
      mismatch in one case (5%), and bidirectional incompatibility in two cases.
      Neutrophil recovery was not significantly different between the ABO-compatible
      and ABO-incompatible groups (p=0.85). At 30 days after transplantation, 12 of 19
      patients tested (63%) had engraftment with all cells of donor origin (100%
      chimeric), and continued to be fully chimeric on day 100+ evaluations. Patients
      with major/bidirectional ABO incompatibility required more red blood cell and
      platelet units after transplantation and were transfused for longer periods of
      time, as compared with patients with minor or no ABO incompatibility. Transient,
      mild haemolysis was noted in one patient between days 10 and 30. Graft-versus
      Host Disease, disease progression and transplant-related mortality were not
      affected by ABO matching. DISCUSSION: Although delayed red blood cell engraftment
      and increased transfusion requirements were documented, in this study ABO
      incompatibility after the RIC protocol used did not impair the clinical outcome.

PMID- 21084016
TI  - Replacement therapy with recombinant factor IX. A multicentre evaluation of
      current dosing practices in Italy.
AB  - BACKGROUND: The in vivo recovery of recombinant factor IX (rFIX) is reported to
      be lower than that of plasma-derived products, with potential clinical
      implications for dosing. In clinical practice, a conversion (augmentation) factor
      is suggested to calculate the necessary doses of rFIX. The aim of this study was
      to assess the range of values for the conversion factor in usual clinical
      practice in Italy. MATERIALS AND METHODS: The study was questionnaire-based and
      proposed to all Italian Haemophilia centres treating patients with haemophilia B.
      Age, weight, dosage used in the last effective infusion, treatment regimen
      (prophylaxis versus on-demand), human immunodeficiency virus (HIV) and hepatitis
      C virus (HCV) status, and years of previous therapy with rFIX were recorded for
      patients with severe haemophilia B treated with rFIX. Mean, standard deviation,
      median and range were calculated for demographic and treatment data for the
      overall population and for subgroups. The conversion factor for the theoretical
      dosage of 40 IU/Kg was calculated. RESULTS: Among 207 patients with severe
      haemophilia B being followed in 24 centres, 138 (66.7%) were being treated with
      rFIX. The sample of 207 patients represents 83.1% of the population of Italian
      patients with severe haemophilia B. The age range of the studied patients was 0
      72 years (mean, 24 years) and the weight range was 3-108 kg (mean, 60 kg).
      Nineteen patients (14.4%) were positive for HIV and 51 (42.9%) were positive for
      HCV. The mean dosage of rFIX was 44 IU/Kg, with no significant difference between
      those receiving the product as prophylaxis or on-demand. A reduction in dosage
      was observed with increasing age (0.23 IU/kg/year). The mean value for the
      conversion factor was 1.10 +/- 0.36 (median 1.00, range 0.51-2.08), when
      estimated for the whole population. No effect of HIV and HCV status was found on
      the dose prescribed. No evident correlation was found with the underlying genetic
      mutation. DISCUSSION: We found that dosing of rFIX in clinical practice is very
      close to that of plasma-derived FIX concentrates. As a consequence, dosing in the
      non-surgical setting should be started using the same criteria as those for
      plasma-derived FIX and treatment effectiveness verified on a clinical basis
      rather than relying on in vivo recovery assessments.

PMID- 21084017
TI  - Self-perceived health status in blood donors.
AB  - BACKGROUND: Relationships between self-perceived health status and mortality,
      morbidity, disability and health care utilisation have been well established. The
      self-perceived health status of blood donors has, however, never been assessed.
      MATERIALS AND METHODS: Using the Short-Form 12 questionnaire, we assessed self
      perceived health status in a sample of blood donors. RESULTS: The mean values for
      the Physical Component Summary (PCS) score were similar for males and females,
      being 54 versus 54.12, respectively. There was, however, a gender difference for
      the Mental Component Summary (MCS) score, with women reporting a lower mean
      score. Young blood donors had the lowest mean score for the MCS, without gender
      differences. In all the other age categories, males had higher scores. Education
      did not seem to be as relevant as previously indicated in the literature. Our
      sample of blood donors included a certain number of overweight and obese
      subjects. The PCS scores were lowest in obese males and females. The highest MCS
      score was found in the group of overweight males. CONCLUSION: Further research in
      this selected population could be indicated as a new way to improve understanding
      of self-perceived health status and the determinants of the intention to become
      or to remain a blood donor.

PMID- 21084018
TI  - Albumin is not a buffer in plasma.

PMID- 21084019
TI  - The origins of Western dermatology.
AB  - OBJECTIVE: On the premise that historical background makes the present more
      understandable, this review covers the origins of Western dermatology from its
      Greek and Roman origins through the Middle Ages to the defining moments in the
      late eighteenth century.BACKGROUND AND CONCLUSION:The development of major
      European centers at this time became the background for future centers in the
      eastern United States in the midnineteenth century and, finally, to the West
      Coast of the United States and Canada by the midtwentieth century.

PMID- 21084020
TI  - Canadian hand dermatitis management guidelines.
AB  - BACKGROUND: Hand dermatitis (HD) is one of the most common skin conditions;
      however, it is not a homogeneous disease entity. The severity of HD may range
      from very mild cases to severe chronic forms, which may result in prolonged
      disability and, occasionally, refractory HD. Chronic hand dermatitis (CHD) is
      associated with a high health- economic burden and significant loss of quality of
      life. OBJECTIVE: Although numerous treatment options are available, the
      management of CHD is often difficult and unsatisfactory. There is a paucity of
      well-designed, randomized, controlled clinical trials in support of the efficacy
      of established treatment modalities. CONCLUSION: These guidelines cover the
      epidemiology, burden, quality of life, etiology, diagnosis, classification, and
      prevention of HD and provide guidance on management using an approach that is as
      evidence based as possible.

PMID- 21084021
TI  - Skin disease and stigma in emerging adulthood: impact on healthy development.
AB  - BACKGROUND: Visible skin disorders can limit healthy psychosocial development in
      several domains owing to the stigma these disorders create. OBJECTIVE: To assess
      if emerging adults with acne and eczema perceive stigma in diverse developmental
      domains resulting from their visible skin conditions. METHODS: A convenience
      sample of 336 emerging adults attending a diverse public university in northern
      California completed a Web-based survey. Multivariate modeling was used to
      determine if eczema and acne result in perceived stigma. RESULTS: The mean (SD)
      age of respondents was 20.1(1.5) years; most were white (43.2%) and female
      (62.5%). Almost half (47%) reported acne and 16.4% reported eczema. The
      likelihood of experiencing perceived stigma was 1.6 (95% CI 1.13-2.27, p < .001)
      times higher for those with eczema compared to those without eczema, and the
      likelihood of experiencing perceived stigma was 3.19 (95% CI 2.41-4.22, p <
      .0001) times higher for those with acne compared to those without acne.
      CONCLUSIONS: Our findings indicate that emerging adults perceive stigma as a
      result of their acne and eczema in several important developmental domains. The
      results suggest that acne may have a stronger relationship with perceived stigma
      than eczema, perhaps owing to its greater visibility on the body. University
      based activities are recommended to support those with skin disease.

PMID- 21084022
TI  - ICOS gene polymorphism may be associated with pemphigus.
AB  - BACKGROUND: Pemphigus is an autoimmune blistering disease mediated by circulating
      IgG autoantibodies directed against desmogleins 3 and/or 1. As pemphigus is a T
      cell-mediated disease, one may assume that genetically determined disregulation
      of costimulatory signal may be involved in its pathogenesis. OBJECTIVE: The aim
      of the present study was to evaluate the relationship between polymorphisms in
      genes encoding costimulatory receptors, CTLA4 and ICOS, and pemphigus in the
      Polish population. METHODS: The study included 54 patients with pemphigus: 40
      with pemphigus vulgaris (PV) and 14 with pemphigus foliaceus (PF). Additionally,
      176 healthy unrelated blood donors served as controls. +49A/G CTLA4 and IVS1+173
      ICOS polymorphisms were identified using a modified polymerase chain reaction
      restriction fragment-length polymorphism. RESULTS: Analysis of the frequency of
      genotypes and alleles of +49A/G CTLA4 gene polymorphism showed no statistically
      significant differences between the PV and PF patients and the controls. The
      distribution of genotypes in IVS1+173 ICOS polymorphisms was significantly
      different in both PV (p < .01) and PF (p  =  .0004) patients when compared to
      controls. The carriers of the allele C were more frequent in PV or PF in
      comparison with the control group (p < .001 for both groups). CONCLUSIONS: Our
      results suggest that genetically determined abnormal function of costimulatory
      receptors in T cells may be associated with the pathogenesis of pemphigus.

PMID- 21084023
TI  - Anatomic location of Basal cell carcinomas may favor certain histologic subtypes.
AB  - BACKGROUND: Differences in age, site, and subtype exist in basal cell carcinoma
      (BCC). OBJECTIVE: To evaluate whether an independent association exists between
      the anatomic location and the histologic subtype of BCC. MATERIALS AND METHODS: A
      series of 3,254 BCCs was examined. The location was the head/neck (n  =  1,766),
      limbs (n  =  362), trunk (n  =  1,113), or genitals (n  =  13). Subtype was
      classified as superficial, nodular, micronodular, morpheic-infiltrative, or
      fibroepithelial. RESULTS: Prevalence of BCCs on the head/neck or chest/abdomen
      increased with age (p < .001). The prevalence of superficial subtype decreased
      with age (p < .0001), whereas the prevalence on nodular subtype increased (p <
      .0001). Subtype was associated with location (p < .0001). The prevalence of
      superficial subtype was lower among BCCs on the head/neck than other locations
      (24.9% vs 64.4%, OR 0.18, 95% CI 0.16-0.21). The prevalence of nodular or
      morpheic/infiltrative subtype was higher among BCCs on the head/neck than other
      locations, that is, 57.1% versus 29.2%, OR 3.23, 95% CI 2.79 to 3.74 (nodular)
      and 16.1% versus 4.0%, OR 4.56, 95% CI 3.42 to 6.08 (morpheic/infiltrative).
      CONCLUSION: Anatomic location and subtype of BCC were associated with age, but
      the anatomic location was the only independent predictor of histologic subtype.
      Although a bias by referral patterns may not be excluded, the results suggest
      that the anatomic location may favor the development of particular BCC subtypes.

PMID- 21084024
TI  - Successful treatment of atrophic scars from cutaneous leishmaniasis using a
      fractional laser.
AB  - BACKGROUND: Cutaneous leishmaniasis can lead to unsightly atrophic scars, which
      have limited treatment options. There is a scarcity of literature on its
      treatment modalities. Fractional lasers have been successfully used in treating a
      variety of skin conditions with minimal downtime and side effects. METHODS: We
      report a successful treatment of a 25-year-old female patient with an atrophic
      scar from cutaneous leishmaniasis on the nose with a fractional laser (Fraxel
      Re:store SR 1500). Ten treatment sessions were performed at a pulse energy of 45
      to 70 mJ. The treatment response was assessed by comparing pre- and posttreatment
      clinical photographs. RESULTS: After three sessions, the patient observed 40%
      improvement. More than 90% improvement was noticed after the tenth session. No
      significant adverse effects were noted. The improvement was persistent at the 3
      month follow-up. CONCLUSION: The excellent improvement in this patient should
      encourage further studies to achieve more efficacy and optimize the treatment
      parameters.

PMID- 21084025
TI  - Drug-induced lichenoid dermatitis with histopathologic features of mycosis
      fungoides in a patient with psoriasis.
AB  - BACKGROUND: With recent advancements in the understanding of psoriasis, treatment
      has evolved toward more targeted therapy in the form of biologics. Although
      generally safe and well tolerated, various adverse reactions may occur with the
      use of biologics. OBJECTIVES: The objective of this article is to present a case
      of a biologic-induced drug eruption initially presenting with histopathologic
      features of mycosis fungoides (MF). METHODS AND RESULTS: A 47-year-old male
      presented with an extensive erythematous macular eruption approximately 14 hours
      after a single dose of etanercept. Histopathology initially revealed a lichenoid
      dermatitis with features of MF, but immunohistopathology later refuted the
      presence of MF. CONCLUSIONS: It is important for clinicians to be aware that
      adverse cutaneous reactions with biologic therapy may initially present with
      histopathologic features of MF.

PMID- 21084026
TI  - Chemical leukoderma induced by herbal oils.
AB  - BACKGROUND: Chemical leukoderma (CL) may result from repeated exposure to
      specific chemical compounds such as industrial chemicals, cosmetics, and personal
      articles. The incidence of CL is reportedly increasing rapidly in developing
      countries. OBJECTIVE: Two cases of chemical leukoderma arising out of use of
      herbal oils on the scalp and breasts are described. CONCLUSION: We emphasize the
      importance of a detailed history regarding possible exposure to chemical agents
      in patients with depigmented lesions, mainly in adults.

PMID- 21084028
TI  - Experimental evaluation of depth-of-interaction correction in a small-animal
      positron emission tomography scanner.
AB  - Human and small-animal positron emission tomography (PET) scanners with
      cylindrical geometry and conventional detectors exhibit a progressive reduction
      in radial spatial resolution with increasing radial distance from the geometric
      axis of the scanner. This "depth-of-interaction" (DOI) effect is sufficiently
      deleterious that many laboratories have devised novel schemes to reduce the
      magnitude of this effect and thereby yield PET images of greater quantitative
      accuracy. Here we examine experimentally the effects of a particular DOI
      correction method (dual-scintillator phoswich detectors with pulse shape
      discrimination) implemented in a small-animal PET scanner by comparing the same
      phantom and same mouse images with and without DOI correction. The results
      suggest that even this relatively coarse, two-level estimate of radial gamma ray
      interaction position significantly reduces the DOI parallax error. This study
      also confirms two less appreciated advantages of DOI correction: a reduction in
      radial distortion and radial source displacement as a source is moved toward the
      edge of the field of view and a resolution improvement detectable in the central
      field of view likely owing to improved spatial sampling.

PMID- 21084027
TI  - Nanoparticles for biomedical imaging: fundamentals of clinical translation.
AB  - Because of their large size compared to small molecules and their
      multifunctionality, nanoparticles (NPs) hold promise as biomedical imaging,
      diagnostic, and theragnostic agents. However, the key to their success hinges on
      a detailed understanding of their behavior after administration into the body. NP
      biodistribution, target binding, and clearance are complex functions of their
      physicochemical properties in serum, which include hydrodynamic diameter,
      solubility, stability, shape and flexibility, surface charge, composition, and
      formulation. Moreover, many materials used to construct NPs have real or
      potential toxicity or may interfere with other medical tests. In this review, we
      discuss the design considerations that mediate NP behavior in the body and the
      fundamental principles that govern clinical translation. By analyzing those
      nanomaterials that have already received regulatory approval, most of which are
      actually therapeutic agents, we attempt to predict which types of NPs hold
      potential as diagnostic agents for biomedical imaging. Finally, using quantum
      dots as an example, we provide a framework for deciding whether an NP-based agent
      is the best choice for a particular clinical application.

PMID- 21084029
TI  - Click synthesis and biologic evaluation of (R)- and (S)-2-amino-3-[1-(2
      [18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid for brain tumor imaging
      with positron emission tomography.
AB  - The (R)- and (S)-enantiomers of 2-amino-3-[1-(2-[18F]fluoroethyl)-1H
      [1,2,3]triazol-4-yl]propanoic acid (4) were synthesized and evaluated in the rat
      9L gliosarcoma brain tumor model using cell uptake assays, biodistribution
      studies, and micro-positron emission tomography (microPET). The (R)- and (S)
      enantiomers of [18F]4 were radiolabeled separately using the click reaction in
      57% and 51% decay-corrected yields, respectively. (S)-[18F]4 was a substrate for
      cationic amino acid transport and, to a lesser extent, system L transport in
      vitro. In vivo biodistribution studies demonstrated that (S)-[18F]4 provided
      higher tumor uptake and higher tumor to brain ratios (15:1 at the 30- and 60
      minute time points) compared to the (R)-enantiomer (7:1 at the 30- and 60-minute
      time points). MicroPET studies with (S)-[18F]4 confirmed that this tracer
      provides good target to background ratios for both subcutaneous and intracranial
      9L gliosarcoma tumors. Based on these results, the 1H-[1,2,3]triazole-substituted
      amino acid (S)-[18F]4 has promising PET properties for brain tumors and
      represents a novel class of radiolabeled amino acids for tumor imaging.

PMID- 21084030
TI  - Evaluation of the reversal of multidrug resistance by MDR1 ribonucleic acid
      interference in a human colon cancer model using a Renilla luciferase reporter
      gene and coelenterazine.
AB  - The reversal effect of multidrug resistance (MDR1) gene expression by adenoviral
      vector-mediated MDR1 ribonucleic acid interference was assessed in a human colon
      cancer animal model using bioluminescent imaging with Renilla luciferase (Rluc)
      gene and coelenterazine, a substrate for Rluc or MDR1 gene expression. A
      fluorescent microscopic examination demonstrated an increased green fluorescent
      protein signal in Ad-shMDR1- (recombinant adenovirus that coexpressed MDR1 small
      hairpin ribonucleic acid [shRNA] and green fluorescent protein) infected HCT
      15/Rluc cells in a virus dose-dependent manner. Concurrently, with an increasing
      administered virus dose (0, 15, 30, 60, and 120 multiplicity of infection), Rluc
      activity was significantly increased in Ad-shMDR1-infected HCT-15/Rluc cells in a
      virus dose-dependent manner. In vivo bioluminescent imaging showed about 7.5-fold
      higher signal intensity in Ad-shMDR1-infected tumors than in control tumors (p <
      .05). Immunohistologic analysis demonstrated marked reduction of P-glycoprotein
      expression in infected tumor but not in control tumor. In conclusion, the
      reversal of MDR1 gene expression by MDR1 shRNA was successfully evaluated by
      bioluminescence imaging with Rluc activity using an in vivo animal model with a
      multidrug resistance cancer xenograft.

PMID- 21084031
TI  - Gastroenteropancreatic neuroendocrine tumors: standardizing therapy monitoring
      with 68Ga-DOTATOC PET/CT using the example of somatostatin receptor radionuclide
      therapy.
AB  - The purpose of this study was to standardize therapy monitoring of hepatic
      metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during
      the course of somatostatin receptor radionuclide therapy (SRRT). In 21
      consecutive patients with nonresectable hepatic metastases of GEP-NETs,
      chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the
      last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of
      normal liver and hepatic metastases were calculated. In addition, the volumes of
      hepatic metastases (volume of interest [VOI]) were measured using four cut-offs
      to separate normal liver tissue from metastases (SUVmax of the normal liver plus
      10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV  =  10
      [VOI10SUV]). The SUVmax of the normal liver was below 10 (7.2 +/- 1.3) in all
      patients and without significant changes. Overall therapy changes (Delta) per
      patient (mean [95% CI]) were statistically significant with p < .01 for DeltaCgA 
      =  -43 (-69 to -17), DeltaSUVmax  =  -22 (-29 to-14), and DeltaVOI10SUV  =  -53 (
      68 to -38)% and significant with p < .05 for DeltaVOIliver+10%  =  -29 (-55 to 
      3)%, DeltaVOIliver+20%  =  -32 (-62 to -2) and DeltaVOIliver+30%  =  -37 (-66 to 
      8). Correlations were found only between DeltaCgA and DeltaVOI10SUV (r  =  .595;
      p < .01), DeltaSUVmax and DeltaVOI10SUV (0.629, p < .01), and SUVmax and
      DeltaSUVmax (r  =  -.446; p < .05). 68Ga-DOTATOC PET/CT allows volumetric therapy
      monitoring via an SUV-based cut-off separating hepatic metastases from normal
      liver tissue (10 SUV recommended).

PMID- 21084033
TI  - Excessive medical information increase in package inserts.
AB  - OBJECTIVES: Package inserts are the most frequent source of patient information
      about medicines aside from doctors and pharmacists. MATERIALS AND METHODS: A
      representative selection of 271 German package inserts available in 2005 was
      investigated, using 152 validated quality criteria and by measuring 242 further
      values. RESULTS: A significant increase in package insert texts over recent years
      was found; standing at an average of 2,005 words. This is associated with the
      significant increase in complicated medical information being communicated; with
      on an average of 114.1 difficult words and 46.3 non quantifiable phrases per
      package insert. Only 60.1% of the package inserts offered all dosages as number
      of tablets or other amounts of the ready to use medicine, while just 29.5% listed
      the maximum daily dose for all users. 54.6% provided actions for all possible
      side effects and 24.2% the frequencies of side effects in numerical form.
      CONCLUSION: The significantly increased volume of medical information provided in
      package inserts does not meet the requirements of patients. Major efforts are
      required by pharmaceutical companies, authorities and legislative bodies in order
      to reduce information to that which is essential for patients and to ensure that
      this is provided in short, precise and easily comprehensible texts.

PMID- 21084034
TI  - Population pharmacokinetic analysis of the active product of dipyrone.
AB  - OBJECTIVE: Pharmacokinetics of 4-methyl-amino-antipyrine (MAA), the active
      metabolite of the nonsteroidal anti-inflammatory agent dipyrone, whose time
      course correlates to the therapeutic effect of the drug, are studied. STUDY
      DESIGN AND SETTING: 153 patients hospitalized in the Department of Medicine at
      the Hadassah University Hospital, Jerusalem, Israel. INTERVENTION: Patients
      receiving dipyrone for the treatment of fever or pain were asked to participate
      in the study. Pharmacokinetics and statistical analysis: Using the population
      approach based on a formerly developed experimental model, the relationships
      between pharmacokinetic parameters and demographic and physiological covariates
      are explored. RESULTS: The results of the analysis show considerable variability
      in pharmacokinetics across the study population, and a significant decrease in
      clearance with age. CONCLUSION: A population pharmacokinetic analysis of MAA, the
      active product of dipyrone, reveals that age is a significant predictor of MAA
      disposition. Covariates that measure hepatic and renal function do not appear to
      be good predictors of the rate of MAA disposition.

PMID- 21084035
TI  - Atorvastatin-induced acute elevation of hepatic enzymes and the absence of cross
      toxicity of pravastatin.
AB  - Atorvastatin has been associated with liver injury. We reported here two cases of
      aminotransferases elevation within 12 h of low-dose atorvastatin therapy. Liver
      functions were fully recovered to the baseline level 11 days after
      discontinuation of atorvastatin treatment. The possible relative risk factors
      included advanced age, chronic and systemic diseases, and co-administration of
      cytochrome P450 3A (CYP3A) enzyme-dependent metabolic drugs or its inhibitors
      such as clopidogrel and diltiazem. No significant transaminase elevation was
      observed after switching to pravastatin. Thus, pravastatin might be safer than
      atorvastain in patients with chronic or systemic diseases, or with co
      administration of CYP3A enzyme-dependent drugs.

PMID- 21084036
TI  - The efficacy of oxymetholone in combination with erythropoietin on hematologic
      parameters and muscle mass in CAPD patients.
AB  - OBJECTIVES: To determine the efficacy of oxymetholone, an androgenic steroid, in
      combination with rHuEPO on hematologic and muscle mass in CAPD patients. METHODS:
      A double-blinded, placebo-controlled experimental study was conducted for 6
      months and 24 CAPD patients were divided into two groups. The treatment group (n
      = 11) received rHuEPO plus oral oxymetholone (50 mg/tablet twice daily). The
      placebo group (n = 13) received rHuEPO plus a placebo twice daily. The evolution
      of the patients' hematologic parameters and the impact of the drugs on their
      muscle mass were evaluated. RESULTS: After 6 months of therapy, hematocrit and
      hemoglobin values of the treatment group were significantly different from those
      of the placebo group (38.1 +/- 1.0% and 32.8 +/- 0.9%, p = 0.001; 12.9 +/- 0.3
      g/dl and 11.0 +/- 0.3 g/dl, p = 0.001 for hematocrit and hemoglobin,
      respectively). The increase in hematocrit and hemoglobin values observed in
      treatment group was statistically greater than those of the placebo group (p <
      0.01). After 6 months, none of anthropometric parameters, albumin, protein or
      lean body mass levels, were significantly different from baseline in the placebo
      group. Conversely, most of the anthropometric parameters, albumin and lean body
      mass levels were significantly increased in the oxymetholone group (p < 0.05).
      The mean weight of subjects in the oxymetholone group changed from 63.82 +/- 2.71
      to 67.02 +/- 3.26 kg (p = 0.001). The subjective global assessment score for 7
      patients in the treatment group (63.6%) changed in a positive manner. A rise in
      liver enzymes was the main side effect observed in the treatment group.
      CONCLUSIONS: Oxymetholone significantly enhances the erythropoietic effects of
      rHuEPO and improves the nutritional status of CAPD patients. However, significant
      increases in liver enzymes need to be monitored closely.

PMID- 21084037
TI  - Evaluation of methylprednisolone aceponate, tacrolimus and combination thereof in
      the psoriasis plaque test using sum score, 20-MHz-ultrasonography and optical
      coherence tomography.
AB  - BACKGROUND: Despite new treatment options with systemic disease modifiers,
      topical therapy - especially as combination therapy - plays an important role in
      psoriasis treatment. METHODS: Antipsoriatic efficacy of methylprednisolone
      aceponate ointment (MPA), tacrolimus 0.1% ointment (FK506) and their combination
      (MPA+FK506) were investigated in a double-blind randomized pilot study using the
      psoriasis plaque test. Agents and corresponding placebos were applied once daily
      under occlusion for 11 days. Test sites were evaluated by sum score (erythema,
      scaling, infiltration), objective assessment by 20-MHz-sonography and optical
      coherence tomography (OCT). RESULTS: After 11 days, the sum score significantly
      improved from baseline value in FK506-treated skin (9.6 vs. 2.9, p < 0.0001). MPA
      led to a significant improvement of the sum score (9.4 vs. 0.6, p < 0.0001).
      Combination therapy showed results similar to MPA monotherapy (9.4 vs. 0.4, p <
      0.0001). These findings were confirmed by 20-MHz-sonography and OCT data.
      CONCLUSION: FK506 is moderately effective in chronic plaque-type psoriasis in our
      model. Combination therapy with FK506+MPA has no additive effect compared to MPA
      alone.

PMID- 21084038
TI  - Avoiding concomitant prescription of drugs with a potential for interaction:
      mission impossible?
AB  - OBJECTIVE: The increased prevalence of multi-drug therapy increases the risk of
      drug interactions. We conducted a study with the aim of evaluating the prevalence
      of prescribing potentially interacting drug combinations, their severity,
      mechanism, and in particular, their clinical relevance, in medical inpatients at
      two Croatian university hospitals. METHODS: A cross-sectional study was conducted
      that included all medical inpatients receiving >= 2 drugs. Data were analyzed for
      200 predefined drug-drug combinations compiled from the Micromedex data-base and
      literature. Two rating scales were used, one indicating the severity of a
      potential drug-drug interaction (pDDI) (minor, moderate, major), and the other
      assessing its clinical relevance (1: contraindicated; 2: avoidable; 3: consider
      risk-benefit ratio; 4: hardly avoidable). RESULTS: The prescribing patterns were
      similar between evaluated hospitals. The prevalence of pDDIs was 46%. The mean
      number of drugs prescribed per patient was 6.2 (+/- 95% CI 5.9 - 6.5). Out of 200
      predefined pDDIs, 96 were found in our study population with mean 2.8 pDDIs per
      patient (+/- 95% CI 2.4 - 3.1). Out of 478 single identified pDDIs, most were of
      moderate and major severity (56% and 33%, respectively). However, only 9% out of
      them were considered completely avoidable, 57% were considered hardly avoidable,
      and for 35% the consideration of risk-benefit ratio was recommended. Most pDDIs
      were classified as pharmacodynamic by mechanism of interaction (45%). Age and
      number of prescribed drugs were significant risk factors for prescription of
      potentially interacting drug combinations (OR 1.01 (+/- 95% CI 1.001 - 1.03) and
      OR 1.46 (+/- 95% CI 1.33 - 1.59), respectively). CONCLUSIONS: Despite the high
      prevalence of pDDIs, only 1 in 10 was considered avoidable.

PMID- 21084039
TI  - Population pharmacokinetics of ustekinumab in patients with active psoriatic
      arthritis.
AB  - PURPOSE: To characterize the population pharmacokinetics of subcutaneous
      ustekinumab, a human IgG1Kappa; monoclonal antibody against interleukin-12/23p40,
      using data from a randomized, double-blind, placebo-controlled Phase II study in
      patients with active psoriatic arthritis (PsA). METHODS: A total of 786
      quantifiable serum ustekinumab concentrations from 130 patients were analyzed
      using a nonlinear mixed-effects modeling approach. A 1-compartment model with
      first-order absorption and elimination was selected as the structural model.
      RESULTS: The population typical mean (percent relative standard error (%RSE))
      values for apparent clearance (CL/F), apparent volume of distribution (V/F), and
      absorption rate constant (ka) obtained from the final covariate model were 0.465
      l * day-1 (5.1%), 14.3 l (4.4%), and 0.427 day-1 (3.9%), respectively. The
      between-subject variability in CL/F, V/F, and ka were 53.9%, 42.3%, and 82.4%,
      respectively. Patient body weight and antibody-to-ustekinumab status were
      significant covariates affecting the CL/F and/or V/F of ustekinumab. None of the
      other factors evaluated, such as age, sex, race, baseline disease
      characteristics, concomitant methotrexate or nonsteroidal anti-inflammatory
      drugs, and past use of immunosuppressives, biologics, systemic corticosteroids,
      or disease-modifying antirheumatic drugs, were found to have significant effects
      on the pharmacokinetics of ustekinumab. CONCLUSION: The pharmacokinetics of
      ustekinumab in patients with PsA are comparable to those in patients with
      moderate-to-severe plaque psoriasis which was previously investigated.

PMID- 21084040
TI  - Assessment of oral midazolam limited sampling strategies to predict area under
      the concentration time curve (AUC) during cytochrome P450 (CYP) 3A baseline,
      inhibition and induction or activation.
AB  - A previous study reported a 2- and 3-timepoint limited sampling strategy (LSS)
      model accurately predicted oral midazolam area under the concentration time curve
      (AUC), and thus cytochrome P450 (CYP) 3A activity. OBJECTIVE: This study
      evaluated whether the LSS models predict midazolam AUC during CYP3A baseline,
      inhibition and induction/activation. MATERIALS AND METHODS: Plasma midazolam
      concentrations from 106 healthy adults from 6 published studies were obtained
      where oral midazolam was co-administered alone or with ketoconazole, double
      strength grapefruit juice, Ginkgo biloba extract, pleconaril, or rifampin.
      Observed and predicted midazolam AUCs were determined. Bias and precision of the
      LSS models were determined. RESULTS: Contrasting results were observed for the 2-
      and 3-timepoint LSS models in accurately predicting midazolam AUC during baseline
      CYP3A conditions. With the exception of 1 study (single dose, double-strength
      grapefruit juice), the 2- and 3-timepoint LSS models did not accurately predict
      midazolam AUC during conditions of CYP3A inhibition and induction/activation.
      CONCLUSION: The previously reported 2- and 3-timepoint oral midazolam LSS models
      are not applicable to the evaluated conditions of CYP3A baseline, inhibition, and
      induction/ activation.

PMID- 21084041
TI  - Appropriate use of oral drops: perception of health professionals and assessment
      of package insert information.
AB  - OBJECTIVES: To evaluate the perception of health professionals and industry
      personnel towards the appropriate use of oral drops and to assess their package
      inserts with regard to presence of proper instructions for use and storage.
      METHODS: The first part was a cross-sectional self-administered questionnaire.
      The questionnaires were distributed randomly to physicians, pharmacists and
      decision makers in local pharmaceutical companies. In the second part, the
      package inserts of medications with oral drops were reviewed to check for
      presence of proper instructions for storage and proper use. RESULTS: The majority
      of physicians and pharmacists (73.3% and 71.2%) thought that oral drops can be
      delivered from the dropper directly into the patient's mouth. 60.8% of physicians
      and 54.3% of pharmacists thought that the dropper should be clamped vertically
      when oral drop are dispensed. 72.7% of industry personnel agreed that the angle
      of inclination affects the drop size. Many of these personnel said their
      companies did not perform the recommended tests for dose uniformity and
      calibration. Instructions for storage and proper use were not available in
      package inserts of many oral drop products in Palestine. CONCLUSIONS: Health
      professionals should have complete and correct information regarding all factors
      that affect the proper delivery of oral drops and should counsel patients on the
      proper method of delivery. Pharmaceutical companies should take into
      consideration the formulation issues that may affect drop size and provide
      leaflets and labels with complete and correct instructions on the proper use and
      storage of oral drops. Package insert information in oral drops needs to be more
      comprehensive with regard to instructions for use and storage.

PMID- 21084042
TI  - Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 
      800 ug in healthy volunteers.
AB  - OBJECTIVES: Fentanyl pectin nasal spray (FPNS) is formulated as a solution
      utilizing PecSys(r); pectin based enabling technology (Archimedes). On contact
      with the nasal mucosa the formulation will gel and modulate fentanyl absorption
      while limiting nasal drip or runoff. This single-dose volunteer study compared
      the pharmacokinetics of FPNS 100, 200, 400, and 800 ug doses and assessed
      bioavailability relative to oral transmucosal fentanyl (OTFC) 200 ug. Safety and
      dose proportionality were also examined. SUBJECTS AND METHODS: 16, opioid-naive
      subjects were dosed on five separate visits under naltrexone block. FPNS doses
      were administered using a Pfeiffer device delivering 100 ul. Devices were filled
      with either 1.57 mg/ml (100 and 200 ug dosing) or 6.28 mg/ml fentanyl citrate
      (400 and 800 ug). Venous blood samples were collected up to 48 h after dosing and
      plasma fentanyl concentrations measured. RESULTS: Median tmax values for FPNS
      ranged from 15 to 21 min post-dose and were dose-independent. At 200 ug Cmax
      values were 2.3-fold higher for FPNS compared with OTFC. Mean relative
      bioavailability of FPNS to OTFC ranged from 103% to 163%. Dose proportionality
      for Cmax and AUC0-1 across the FPNS range was statistically confirmed. Drug
      absorption also increased in a close to dose-proportional manner for AUC0-inf.
      CONCLUSIONS: FPNS has a shorter tmax, higher Cmax and greater bioavailability
      than OTFC and is well tolerated. The dose proportionality of Cmax and AUC0-1 was
      demonstrated. It is concluded that the pharmacokinetic profile of FPNS suggests
      this product is suitable for clinical investigation in breakthrough pain in
      cancer patients.

PMID- 21084043
TI  - A pharmacokinetic and bioequivalence study of Contiflo ICON 400 ug tablets in
      healthy Indian subjects.
AB  - INTRODUCTION: Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits
      selectivity for alpha1 receptors in human prostate. Blockade of these
      adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax,
      resulting in an improvement in urine flow rate and a reduction in symptoms of
      benign prostatic hypertrophy. A new formulation Contiflo ICON 400 ug has been
      developed by Ranbaxy Laboratories Limited, India similar to Flomaxtra XL 400 ug
      of Astellas Pharma Limited, United Kingdom. This product is specifically designed
      to achieve a more consistent plasma concentration over a period of 24-h, a lower
      maximum plasma concentration (Cmax) and an independence of pharmacokinetics (PKs)
      on food intake. METHODS: The objective of the present study was to evaluate the
      pharmacokinetics and bioequivalence of the new formulation Contiflo ICON 400 ug
      of Ranbaxy Laboratories Limited, India and Flomaxtra XL 400 ug prolonged release
      tablets (containing tamsulosin hydrochloride prolonged release 400 ug) of
      Astellas Pharma Limited, United Kingdom. Study was conducted as an open label,
      balanced, randomized, two-treatment, two-period, two-sequence, cross over, single
      dose bioequivalence study in 32 adult male human subjects under fed conditions.
      The mean (range) age, weight and height of the study subjects were 27.03 years
      (19 - 40 years), 57.19 kg (48 - 72 kg) and 166.81 cm (154 - 181 cm) respectively.
      Blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5,
      5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 20, 24, 36, 48, 72, and 96 h post dose in each
      period. Plasma samples were analyzed for tamsulosin by using validated liquid
      chromatographic mass spectrometry (LC-MS/MS) method. RESULTS: The Mean +/- SD of
      pharmacokinetic parameters tmax, Cmax, AUC24, AUClast and AUCinf for Tamsulosin
      were 11.741 +/- 4.7201 and 12.155 +/- 6.3077 h, 10.7614 +/- 4.76709 and 10.4954
      +/- 5.08979 ng/ml, 171.4674 +/- 77.39695 and 160.6738 +/- 77.98628 ng.h/ml,
      262.7771 +/- 150.21432 and 250.6854 +/- 156.75581 ng.h/ml, 280.0702 +/- 152.14253
      and 273.5078 +/- 156.85910 ng.h/ml for test and reference formulations
      respectively. The ratios of least square means and the 90% confidence interval of
      log transformed pharmacokinetic parameter Cmax, AUC24, AUClast and AUCinf were
      within 80 - 125% acceptance range. CONCLUSION: In conclusion, Contiflo ICON 400
      ug tablets developed by Ranbaxy Laboratories Limited is bioequivalent to the
      reference formulation in healthy adult male volunteers under fed condition.

PMID- 21084044
TI  - Clinical and molecular characterization of a family with a dominant renin gene
      mutation and response to treatment with fludrocortisone.
AB  - BACKGROUND: A family was identified with autosomal dominant inheritance of
      anemia, polyuria, hyperuricemia, and chronic kidney disease. Mutational analysis
      revealed a novel heterozygous mutation c.58T > C resulting in the amino acid
      substitution of cysteine for arginine in the preprorenin signal sequence
      (p.cys20Arg) occurring in all affected members. METHODS: Effects of the
      identified mutation were characterized using in vitro and in vivo studies.
      Affected individuals were clinically characterized before and after
      administration of fludrocortisone. RESULTS: The mutation affects endoplasmic
      reticulum co-translational translocation and posttranslational processing,
      resulting in massive accumulation of non-glycosylated preprorenin in the
      cytoplasm. This affects expression of intra-renal RAS components and leads to
      ultrastructural damage of the kidney. Affected individuals suffered from anemia,
      hyperuricemia, decreased urinary concentrating ability, and progressive chronic
      kidney disease. Treatment with fludrocortisone in an affected 10-year-old child
      resulted in an increase in blood pressure and estimated glomerular filtration
      rate. CONCLUSIONS: A novel REN gene mutation resulted in an alteration in the
      amino acid sequence of the renin signal sequence and caused childhood anemia,
      polyuria, and kidney disease. Treatment with fludrocortisone improved renal
      function in an affected child. Nephrologists should consider REN mutational
      analysis in families with autosomal dominant inheritance of chronic kidney
      disease, especially if they suffer from anemia, hyperuricemia, and polyuria in
      childhood.

PMID- 21084045
TI  - The new kidney disease: improving global outcomes (KDIGO) guidelines - expert
      clinical focus on bone and vascular calcification.
AB  - Chronic kidney disease-mineral and bone disorder (CKD-MBD) defines a triad of
      interrelated abnormalities of serum biochemistry, bone and the vasculature
      associated with chronic kidney disease (CKD). The new kidney disease: improving
      global outcomes (KDIGO) guidelines define the quality and depth of evidence
      supporting therapeutic intervention in CKD-MBD. They also highlight where patient
      management decisions lack a strong evidence base. Expert interpretation of the
      guidelines, along with informed opinion, where evidence is weak, may help develop
      effective clinical practice. The body of evidence linking poor bone health and
      reservoir function (the ability of bone to buffer calcium and phosphorus) with
      vascular calcification and cardiovascular outcomes is growing. Treating renal
      bone disease should be one of the primary aims of therapy for CKD. Evaluation of
      the biochemical parameters of CKD-MBD (primarily phosphorus, calcium, parathyroid
      hormone and vitamin D levels) as early as CKD Stage 3, and an assessment of bone
      status (by the best means available), should be used to guide treatment
      decisions. The adverse effects of high phosphorus intake relative to renal
      clearance (including stimulation of hyperparathyroidism) precede
      hyperphosphatemia, which presents late in CKD. Early reduction of phosphorus load
      may ameliorate these adverse effects. Evidence that calcium load may influence
      progression of vascular calcification with effects on mortality should also be
      considered when choosing the type and dose of phosphate binder to be used. The
      risks, benefits, and strength of evidence for various treatment options for the
      abnormalities of CKD-MBD are considered.

PMID- 21084046
TI  - Continuation of cinacalcet immediately after renal transplantation: a prospective
      cohort study.
AB  - BACKGROUND: Cinacalcet is used for treating secondary hyperparathyroidism in
      dialysis patients, but it is currently unknown whether it can safely be continued
      immediately after renal transplantation. METHODS: We prospectively studied renal
      transplant recipients with secondary hyperparathyroidism who were receiving
      cinacalcet before transplantation and continued treatment afterwards (n = 29) at
      a dose of 30 mg/day. Cinacalcet dose was titrated to serum calcium. Patients were
      followed for 6 months. Incidence of hypercalcemia, serum calcium and intact PTH
      (iPTH) were analyzed. Tacrolimus levels, acute rejection rate and renal function
      were compared with an age and sex matched control group. RESULTS: In 16 patients
      hypercalcemia was observed after transplantation. Severe hypercalcemia (>= 2.87
      mmol/l) (n = 4) and hypocalcemia (n = 2) were infrequent. No difference in acute
      rejection rate or renal function between the cinacalcet and the control group was
      found. There also was no clinically relevant influence of cinacalcet on
      tacrolimus levels. CONCLUSIONS: Our study shows that cinacalcet can safely be
      continued immediately after renal transplantation. Studies are needed to
      determine if continuation of cinacalcet is better than early withdrawal. Also,
      the optimum dose of cinacalcet and the long-term effects of cinacalcet after
      renal transplantation must be defined.

PMID- 21084047
TI  - Experience with outpatient computed tomographic-guided renal biopsy.
AB  - Native kidney biopsy is still performed primarily with hospital inpatient
      observation period. Experience with outpatient Computed Tomographic (CT)-guided
      renal biopsy at Yale New Haven Medical Center was studied to assess efficacy and
      safety. A total of 146 outpatient native kidney biopsies were identified between
      1995 and 2001. Records were reviewed for demographics, clinical, and laboratory
      data and details of the procedure. Time of admission to the outpatient unit,
      duration of procedure and post-biopsy observation period were recorded.
      Complications such as bleeding, infection, admission to the hospital,
      transfusion, or intervention for continued bleeding were noted. Mean age was 43.9
      +/- 14.9 years and mean serum creatinine was 1.8 +/- 1.4 mg/dl. Renal size
      averaged 11.4 cm. Post-procedure observation time of 4 - 6 h appeared to be
      adequate. Diagnostic tissue was successfully sampled in 98.6% of cases. Procedure
      was well tolerated with no hemodynamically significant changes. Hematocrit and
      hemoglobin concentration changes averaged 3.6 +/- 2.5% and 1.0 +/- 0.9 mg/dl,
      respectively (p < 0.001). There were no instances of death or need for
      intervention. Transfusion was required in 1 patient while 6 patients had
      detectable bleeding and were hospitalized for observation. Outpatient CT-guided
      kidney biopsy provides adequate tissue and appears to be safe with very low
      complication rates.

PMID- 21084048
TI  - Hepatitis C virus-related kidney disease: various histological patterns.
AB  - BACKGROUND: Although hepatitis C virus (HCV) infection is known to be associated
      with Type 2 cryoglobulinemic glomerulopathy (CG), only a few reports about other
      types of nephropathy have been published. METHODS: 68 HCV antibody positive
      patients in whom renal biopsy had been performed for persistent proteinuria,
      hematuria, and/or renal dysfunction between 1992 and 2008 at our institute were
      included. The histological, clinical and laboratory characteristics including the
      age, gender, hypertension, diabetes mellitus, liver histology (chronic hepatitis
      or liver cirrhosis), HCV-RNA, HCV genotype, splenomegaly, gastroesophageal
      varices, serum creatinine, hemoglobin, platelet count, rheumatoid factor,
      cryoglobulin, IgG, IgA, IgM, CH50, C3, C4, creatinine clearance, 24-h protein
      excretion, and hematuria, between their nephropathy with and without immune
      deposition were compared. RESULTS: Nephropathy was classified into two groups
      based on the detection of immune deposits by immunofluorescence microscopy: i.e.,
      a positive group (n = 39) and a negative group (n = 29). The former group was
      further classified into three types of nephropathy: IgG dominant group (n = 10)
      (including membranous nephropathy (MN)), IgA dominant group (n = 20) (including
      IgA nephropathy (IgAN)), membranoproliferative glomerulonephritis (MPGN) (IgA
      type)), and IgM dominant group (n = 9) (MPGN apart from the IgA type). The latter
      group included diabetic nephropathy (n = 13), focal glomerular sclerosis (n = 4),
      and benign nephrosclerosis (n = 3), malignant nephrosclerosis (n = 1),
      tubulointerstitial nephritis (TIN) (n = 2), minimal change nephrotic syndrome (n
      = 1), cast nephropathy (n = 1), granulomatous TIN (n = 1), and others (n = 3). An
      increased serum IgM level, hypocomplementemia, splenomegaly, thrombocytopenia,
      liver cirrhosis, hematuria, and a high HCV RNA level were features of patients
      with MPGN of IgM dominant group (consistent with "CG"). CONCLUSIONS: Our results
      showed various histological patterns of HCV-related kidney disease and the
      specificity of CG, and revealed that a minority of HCV patients (n = 7) presented
      typical CG, while IgAN, MN, and diabetic nephropathy were more frequent.

PMID- 21084049
TI  - Exocrine pancreatic function in patients with end-stage renal disease.
AB  - AIM: malnutrition is a common problem in patients with end-stage renal disease
      (ESRD). Several studies showed 30 years ago that more than half of patients with
      ESRD suffered from exocrine pancreatic insufficiency. However, the studies never
      investigated whether the functional impairments led to morphological changes of
      the pancreas or to steatorrhea and thus indicating the need for lifelong
      pancreatic enzyme substitution. Our goal was therefore not only to establish the
      frequency but also the severity of exocrine pancreatic insufficiency in
      hemodialysis patients. METHODS: the study included 50 hemodialysis patients with
      no history of acute or chronic pancreatitis or upper abdominal symptoms of
      uncertain origin. All patients with hyperthyroidism, status post-gastrectomy or
      (partial) small bowel resection, or chronic inflammatory bowel disease were
      excluded. In all 50 patients, fecal elastase-1 was determined using two different
      methods (Bioserv Diagnostics and ScheBo Biotech) and fecal fat content and fecal
      weight were measured. RESULTS: mild to moderate exocrine pancreatic insufficiency
      (elastase-1 100 - 200 microg/g stool) was found in 10% of patients. It was not
      correlated with age, sex, and underlying renal disease, duration of hemodialysis,
      or diarrhea and steatorrhea. In no patient was the enzyme content < 100 microg/g
      stool, i.e., it never sank to a level at which pancreatic enzyme substitution
      would have been recommended. Nine patients (18%) had mild diarrhea (200 - 300 g
      stool/ day), and 10 (20%) had mild steatorrhea (7 - 15 g fat/day in the stool).
      Five patients had both diarrhea and steatorrhea. CONCLUSIONS: mild to moderate
      but not severe exocrine pancreatic insufficiency is not infrequent in patients on
      hemodialysis but unlikely to be responsible for malnutrition in ESRD. Non
      pancreas-related steatorrhea is also not uncommon. This finding requires further
      analysis because steatorrhea might influence nutrition, thus potentially opening
      the way to new therapeutic approaches.

PMID- 21084050
TI  - Enhanced degradation of tryptophan in patients on hemodialysis.
AB  - BACKGROUND: Hemodialysis patients often present with increased concentrations of
      tryptophan catabolites perhaps related to an enhanced activity of tryptophan
      degrading enzyme indoleamine 2,3-dioxygenase (IDO) that is inducible by pro
      inflammatory stimuli. The often chronic inflammation and immune activation status
      in dialysis patients may accelerate tryptophan degradation, which could influence
      patients' psychological performance. PATIENTS AND METHODS: In this study, plasma
      concentrations of kynurenine and tryptophan were determined by HPLC in 75
      dialysis patients, aged 65.3 +/- 15.0 years. Forty patients were female, 35 male;
      21 (28%) had diabetes mellitus Type 1 or 2 and 32 (43%) suffered from sleep
      disturbances and/or depression. Their dialysis vintage was 4.26 +/- 4.72 years.
      HPLC results were compared to concentrations obtained from 40 healthy blood
      donors, to immune activation marker neopterin, and to psychological test results
      based on INTERMED scores. RESULTS: Compared to those in healthy controls,
      tryptophan concentrations were decreased in patients. Neopterin, kynurenine and
      the kynurenine to tryptophan ratio (kyn/trp, an index of tryptophan degradation)
      were increased in patients (all p < 0.01). Kyn/trp correlated with neopterin
      concentrations (rs = 0.393, p < 0.01). INTERMED scores were 21.0 + 8.4 and
      slightly higher in females (U = -1.831, p < 0.07); they correlated with
      tryptophan concentrations (rs = -0.227, p < 0.05) but with no other parameter
      studied. Data point to a possible relationship between tryptophan metabolic
      disturbances and psychologic presentation of patients, although only a rather
      weak relationship was found. CONCLUSION: We conclude that tryptophan degradation
      is increased in dialysis patients. The association with increased neopterin
      concentrations indicates activated IDO.

PMID- 21084052
TI  - Acute postinfectious glomerulonephritis associated with Campylobacter jejuni
      enteritis - a case report and review of the literature on C. jejuni's potential
      to trigger immunologically mediated renal disease.
AB  - Kidney disease is a rare complication of Campylobacter jejuni (C. jejuni)
      enteritis. We here present the case of an 18-year-old male patient with crampy
      abdominal pain, vomiting, diarrhea, and fever. Three weeks later urinalysis
      revealed mild proteinuria and hematuria and a marked raise in serum creatinine
      was observed. Renal biopsy demonstrated acute endocapillary glomerulonephritis
      with mesangial IgM (immunoglobuline M) deposits. Extensive workup revealed no
      signs of skin or joint disease, thus excluding Henoch-Schonlein purpura. Due to
      persistent abdominal discomfort further gastro-enterological tests were performed
      and eventually Campylobacter jejuni was isolated from the patient's feces. In the
      absence of other precipitating factors for renal diseases we presumed an
      association between the bacterial infection and this postinfectious
      glomerulonephritis. Over a time period of 6 months the patient's kidney function
      normalized completely. However, long-term prognosis remains unclear. In addition
      to the case report, we conducted a review of the literature with results
      underlining Campylobacter jejuni's potential to trigger various types of immune
      mediated kidney diseases.

PMID- 21084051
TI  - Atypical electrolyte kinetics during an emergency dialysis session in a patient
      with Leriche syndrome.
AB  - A hemodialysis patient suffered from circulation failure due to a low output
      syndrome caused by a hyperkalemia (9.9 micromol/l) with typical ecg signs. An
      emergency hemodialysis was started. After 2 h ecg signs of hypokalemia (2.1
      micromol/l) were detectable. Hemodialysis was stopped. 2 h later, serum potassium
      rose to 6.2 micromol/l. An obturation of the aorta and the inferior caval vein
      with perfusion through collateral vessels of the lower body side was obvious,
      resulting into a faster electrolyte correction in the upper and a delayed
      correction in the lower body side with a rebound in the upper compartment.
      Dialysis time and dialysate potassium (4.0 micromol/l) were increased.
      Furthermore no potassium problems occurred.

PMID- 21084053
TI  - Malignant lymphoma of the kidney mimicking rapid progressive glomerulonephritis.
AB  - Primary renal lymphoma (PRL) is rare and often presents as rapidly progressive
      renal failure. Most cases of PRL are large-cell lymphomas of B-cell lineage.
      Herein, we report a 75-year-old female patient with infiltrative CD20 (+) B-cell
      lymphoma who underwent 4 consecutive courses of chemotherapy with R-CVP
      (rituximab, cyclophosphamide, vincristine, and prednisone) and after 12 sessions
      became free from hemodialysis in good general condition. Her serum creatinine
      level gradually decreased to 4.1 mg/dl with adequate urine output. Unfortunately,
      a relapse of CD20 (-) lymphoma developed rapidly involving other organs. She died
      with severe hospital-acquired pneumonia and febrile neutropenia after the last
      chemotherapy with R-MINE almost 1 year after onset of symptoms. We conclude that
      renal biopsy enables prompt diagnosis in rapidly progressive renal failure and
      immunophenotyping and also staging workup of the lymphoma in case of positive
      biopsy. Though rituximab improved response rate of PRL, it reduced expression of
      CD20. This may relate to frequent relapse/resistance after rituximab therapy and
      poor long-term patient survival.

PMID- 21084055
TI  - Peritonitis after gynecological and gastroscopic examinations in a peritoneal
      dialysis patient.

PMID- 21084054
TI  - Chronic periaortitis associated with membranous nephropathy: clues to common
      pathogenetic mechanisms.
AB  - Chronic periaortitis (CP) is a rare disease hallmarked by the presence of a
      periaortic retroperitoneal fibro-inflammatory tissue which can often cause
      obstructive uropathy. CP is isolated in most cases but it may also be associated
      with other sclerosing inflammatory and immune-mediated diseases. We here present
      the case of a patient who was initially diagnosed as having CP and subsequently
      developed membranous nephropathy and chronic sclerosing sialoadenitis of the
      right parotid gland. As these conditions were all characterized by either
      pronounced infiltration of IgG4-positive plasma cells or marked IgG4 tissue
      deposition, we hypothesize that they are part of the same disease spectrum, and
      discuss the immune-mediated pathogenetic mechanisms potentially shared by these
      conditions. In particular, we consider the role of Th2-mediated immune reactions
      and of immunogenetic factors such as HLA genotype as common determinants of these
      disorders.

PMID- 21084056
TI  - Resistance to Citrus psorosis virus in transgenic sweet orange plants is
      triggered by coat protein-RNA silencing.
AB  - The lack of naturally occurring resistance to Citrus psorosis virus (CPsV) has
      demanded exploitation of a transgenic approach for the development of CPsV
      resistant sweet orange plants. Transgenic sweet orange plants producing intron
      hairpin RNA transcripts (ihpRNA) corresponding to viral cp, 54K or 24K genes were
      generated and analyzed at the molecular and phenotypic levels. Two independent
      CPsV challenge assays demonstrated that expression of ihpRNA derived from the cp
      gene (ihpCP) provided a high level of virus resistance, while those derived from
      54K and 24K genes (ihp54K and ihp24K) provided partial or no resistance. The
      presence of small interfering RNA molecules (siRNAs) in the ihpCP transgenic
      sweet orange plants prior to virus challenge, indicated that CPsV resistance was
      due to pre-activated RNA silencing, but siRNAs accumulation level was not
      directly correlated to the degree of the triggered virus resistance among the
      different lines. However, pre-activation of the RNA-silencing machinery and a
      certain minimum accumulation level of siRNA molecules targeting the viral genome
      are key factors for creating virus-resistant plants. This is the first report of
      resistance in citrus plants against a negative-strand RNA virus as CPsV.

PMID- 21084057
TI  - Identification of McbR as transcription regulator of aecD and genes involved in
      methionine and cysteine biosynthesis in Corynebacterium jeikeium K411.
AB  - The C-S lyase aecD (MetC) from skin corynebacteria plays an important role in
      body odour formation by releasing odoriferous sulfanylalkanols from cysteine
      conjugates in human axilla secretions. The expression of the aecD gene from
      Corynebacterium jeikeium K411, a strain originally isolated from the human
      axilla, was down-regulated in cells grown in minimal medium supplemented with
      methionine. A candidate transcription regulator binding in front of the aecD
      coding region was detected by DNA affinity chromatography and identified as McbR
      by peptide mass fingerprinting. A 16-bp McbR-binding site was localized in the
      mapped promoter region of the aecD gene. The binding of purified McbR protein to
      the 16-bp sequence motif was demonstrated by DNA band shift assays. Comparative
      DNA microarray hybridizations and bioinformatic motif searches revealed the gene
      composition of the McbR regulon from C. jeikeium, including 28 genes that are
      organized in 16 transcription units. The McbR protein from C. jeikeium K411
      directly regulates genes involved in methionine uptake and biosynthesis, in
      cysteine biosynthesis and sulfate reduction, and in the biosynthesis of amino
      acids belonging to the aspartate family.

PMID- 21084058
TI  - Immunogenic comparison for two different recombinant chimeric peptides (CP12 and
      CP22) containing one or two copies of three linear B cell epitopes from beta-hCG
      subunit.
AB  - To develop a superior chimeric peptide (CP) vaccine of human chorionic
      gonadotropin (hCG), two CP antigens (named CP12 and CP22) encoding one or two
      copies of three linear B cell epitopes from the beta-hCG subunit and six foreign
      T cell epitopes, including two promiscuous TCEs from hepatitis B surface antigen
      and tetanus toxoid, were constructed and biosynthesized. The hCG CP12 and CP22 of
      21 or 23 kDa, respectively, were expressed in Escherichia coli at the level of
      ~1% of total cell proteins when inserted into thermo-inducible pBV221 expression
      vector. The purified CP12 and CP22 proteins with >95% relative homogeneity are
      immunogenic, and elicited antibodies against the beta5, beta9 and beta8 BCEs of
      beta-hCG in both rabbits and three different inbred strains of mice. A mouse
      uterine weight study in Balb/c mice demonstrated that the CP12 and CP22 antigens
      with an additional beta5 neutralizing epitope enhanced the in vivo bio
      neutralization capacity of the induced antibodies compared to the C-terminal
      immunogen of beta-hCG. We propose that the biosynthesized CP22, possessing with
      two copies of three BCEs, represents a novel candidate antigen for an hCG
      contraceptive or tumor therapeutic vaccine.

PMID- 21084059
TI  - Duchenne muscular dystrophy--what causes the increased membrane permeability in
      skeletal muscle?
AB  - Duchenne muscular dystrophy is a severe muscle wasting disease caused by a
      mutation in the gene for dystrophin--a cytoskeletal protein connecting the
      contractile machinery to a group of proteins in the cell membrane. At the end
      stage of the disease there is profound muscle weakness and atrophy. However, the
      early stage of the disease is characterised by increased membrane permeability
      which allows soluble enzymes such as creatine kinase to leak out of the cell and
      ions such as calcium to enter the cell. The most widely accepted theory to
      explain the increased membrane permeability is that the absence of dystrophin
      makes the membrane more fragile so that the stress of contraction causes membrane
      tears which provide the increase in membrane permeability. However other
      possibilities are that increases in intracellular calcium caused by altered
      regulation of channels activate enzymes, such as phospholipase A(2), which cause
      increased membrane permeability. Increases in reactive oxygen species (ROS) are
      also present in the early stages of the disease and may contribute both to
      membrane damage by peroxidation and to the channel opening. Understanding the
      earliest phases of the pathology are critical to therapies directed at minimizing
      the muscle damage.

PMID- 21084060
TI  - Golgi membranes from liver express an ATPase with femtomolar copper affinity,
      inhibited by cAMP-dependent protein kinase.
AB  - Copper-stimulated P-type ATPases are essential in the fine-tuning of
      intracellular copper. In the present work we characterized a copper-dependent
      ATPase hydrolysis in a native Golgi-enriched preparation from liver and
      investigated its modulation by cyclic AMP-dependent protein kinase (PKA). The
      very high-affinity Atp7b copper pump presented here shows a K(0.5) for free
      copper of 2.5*10(-17) M in bathocuproine disulfonate/copper buffer and ATP
      hydrolysis was inhibited 50% upon stimulation of PKA pathway, using forskolin,
      cAMP or cholera toxin. Incubation with PKA inhibitor (PKAi(5-24) peptide) raises
      Cu(I)-ATPase activity by 50%. Addition of purified PKA alpha-catalytic subunit
      increases K(0.5) for free copper (6.2*10(-17) M) without modification in the
      affinity for ATP in the low-affinity range of the substrate curve (~1 mM). The
      Hill coefficient for free copper activation also remains unchanged if exogenous
      PKA is added (2.7 and 2.3 in the absence and presence of PKA, respectively). The
      results demonstrate that this high-affinity copper pump in its natural
      environment is a target of the liver PKA pathway, being regulatory
      phosphorylation able to influence both turnover rate and ion affinity.

PMID- 21084061
TI  - Functional characterization of heterotrimeric G-proteins in rat diaphragm muscle.
AB  - Seven-transmembrane receptors mediate diverse skeletal muscle responses for a
      wide variety of stimuli, via activation of heterotrimeric G-proteins. Herein we
      evaluate the expression and activation of rat diaphragm or cultured skeletal
      muscle G-proteins using [(35)S]GTPgammaS. Total membrane Galpha subunit content
      was 4-7 times higher in rat primary cultured myotubes and L6 cell line than in
      diaphragm (32.6+/-1.2fmol/mg protein) and 7-27% of them were in the active
      conformational state. Immunoprecipitation assay showed equal expression of
      diaphragm Galphas, Galphaq and Galphai/o. Addition of GDP allowed the measurement
      of G-protein activation by different GPCR, including adrenoceptor, adenosine,
      melatonin and muscarinic receptors. Diaphragm denervation resulted in a marked
      increase in both total and active state G-protein levels. Together, the results
      show that [(35)S]GTPgammaS binding assay is a sensitive and valuable method to
      evaluate GPCR activity in skeletal muscle cells, which is of particular interest
      for pharmacological analysis of drugs with potential use in the management of
      respiratory muscle failure.

PMID- 21084062
TI  - Envelope protein E1 as vaccine target for western equine encephalitis virus.
AB  - Western equine encephalitis virus (WEEV) is a mosquito-borne RNA virus which
      causes lethal infection in humans and equines. There are no commercial vaccines
      or anti-WEEV drugs available for humans. We used replication-defective, human
      adenovirus serotype-5 (HAd5) as a delivery vector for developing WEEV vaccine.
      Our previous study found delivery of both E1 and E2 envelope proteins of WEEV by
      HAd5 vector offers complete protection against lethal challenge of WEEV. In this
      paper, we constructed a HAd5-vectored E1 vaccine, Ad5-E1. Mice given single-dose
      vaccination of Ad5-E1 were completely protected against both homologous and
      heterologous WEEV strains. The protection was rapid, which was achieved as early
      as day 7 after vaccination. In addition, Ad5-E1 induced a strong WEEV-specific T
      cell response. Our data suggest E1 is a potential target for developing single
      dose, fast-acting, HAd5-vectored vaccine for WEEV.

PMID- 21084063
TI  - Immunomodulatory activity of fucoidan against aspirin-induced gastric mucosal
      damage in rats.
AB  - Gastric ulcers and related complications associated with the use of non-steroidal
      anti-inflammatory drugs (NSAIDs), such as aspirin, represent a major global
      health problem. In the present study, we investigate the immunological activity
      of fucoidan against aspirin-induced gastric mucosal damage in rats. Thirty-six
      rats were randomly divided into the following, normal (Carboxy methyl cellulose
      0.05 %), aspirin (Asp-400mg/kg) treated, fucoidan alone (Fu-0.02 g/kg, daily for
      14 days) and Fu+Asp. Cytokines, total nitrite and nitrate (NOx) analysis and
      tissue localization of Cyclooxygenase 1, 2 and epidermal growth factor receptor
      (EGFR) were done using Elisa and immunohistochemistry respectively.
      Histopathology of gastric tissue, collagen deposition was performed using
      Hematoxylin and Eosin and Masson's trichrome were performed. Treatment of rats
      with a single dose of aspirin (400mg/kg, orally) led to significant alterations
      in the levels of total nitrite and nitrate (NOx), interleukins (IL-4, 6, 10, 12),
      tumor necrosis factor (TNF-alpha), and interferon gamma (IFN-gamma). Notably,
      collagen deposition in glandular tissue and localization of cyclooxygenase 1, 2,
      and epidermal growth factor were considerably affected in aspirin-treated rats.
      These severities were prevented to a significant extent in rats pretreated with
      fucoidan (0.02 g/kg/day for two weeks orally). Our findings collectively indicate
      that the gastro-protective effect of fucoidan against aspirin-induced ulceration
      in rats is mediated through its immunomodulatory properties.

PMID- 21084065
TI  - An evaluation of a neighborhood-level intervention to a local food environment.
AB  - BACKGROUND: The impact of local availability of healthy foods on dietary intake
      and health has been established. Interventions to local environments are being
      evaluated for their efficacy and sustainability. PURPOSE: The aim of this paper
      is to provide an evaluation of a community-driven approach to transform
      neighborhood healthy food availability. METHODS: The information provided comes
      from minutes of monthly meetings of the partners, newsletters, media, and other
      store and project documentation. In addition, qualitative interviews with key
      stakeholders and co-op members were conducted. All of the participating
      individuals were interviewed during 2008 and analysis took place in 2010. Each
      interview was audio-taped and transcribed to form verbatim transcripts, then
      content analyzed for themes. RESULTS: The implementation phase of the initiative
      had long-standing negative repercussions on the ability of the store to be
      successful because of renting too large a space; not branding the store early;
      early misperceptions by community members about the store; and the changing of
      organizational partners and personnel, which resulted in a lack of leadership for
      the store. Equally important, the lack of project personnel or consultants with
      business experience directly related to operating a food store reverberated into
      issues related to marketing, price structuring, decisions about stocking the
      store, as well as accounting. CONCLUSIONS: Repercussions of these challenges
      included unmet goals in terms of attracting local residents to become members of
      the co-op, low sales levels, and reduced confidence in the long-term
      sustainability of the food cooperative. Approaches to modifications of local food
      environments are likely to require additional resources beyond funding in order
      to secure positive outcomes.

PMID- 21084066
TI  - Active tuberculosis and recent overseas deployment in the U.S. Military.

PMID- 21084064
TI  - 3G11 expression in CD4+ T cell-mediated autoimmunity and immune tolerance.
AB  - 3G11 is a sialylated carbohydrate epitope of the disialoganglioside molecule
      expressed on mouse CD4(+) T cells. Recent research showed that 3G11 expression is
      related to the modulation of T cell function, i.e., 3G11(-) T cells exhibit
      anergic/Treg characteristics and efficiently inhibit autoimmunity in the central
      nervous system. The relationship between 3G11 expression and immune tolerance is
      summarized in this literature review.

PMID- 21084068
TI  - Alcohol risk management in college settings: the safer California universities
      randomized trial.
AB  - CONTEXT: Potentially effective environmental strategies have been recommended to
      reduce heavy alcohol use among college students. However, studies to date on
      environmental prevention strategies are few in number and have been limited by
      their nonexperimental designs, inadequate sample sizes, and lack of attention to
      settings where the majority of heavy drinking events occur. PURPOSE: To determine
      whether environmental prevention strategies targeting off-campus settings would
      reduce the likelihood and incidence of student intoxication at those settings.
      DESIGN: The Safer California Universities study involved 14 large public
      universities, half of which were assigned randomly to the Safer intervention
      condition after baseline data collection in 2003. Environmental interventions
      took place in 2005 and 2006 after 1 year of planning with seven Safer
      intervention universities. Random cross-sectional samples of undergraduates
      completed online surveys in four consecutive fall semesters (2003-2006).
      SETTING/PARTICIPANTS: Campuses and communities surrounding eight campuses of the
      University of California and six in the California State University system were
      utilized. The study used random samples of undergraduates (~500-1000 per campus
      per year) attending the 14 public California universities. INTERVENTION: Safer
      environmental interventions included nuisance party enforcement operations, minor
      decoy operations, driving-under-the-influence checkpoints, social host
      ordinances, and use of campus and local media to increase the visibility of
      environmental strategies. MAIN OUTCOME MEASURES: Proportion of drinking occasions
      in which students drank to intoxication at six different settings during the fall
      semester (residence hall party, campus event, fraternity or sorority party, party
      at off-campus apartment or house, bar/restaurant, outdoor setting), any
      intoxication at each setting during the semester, and whether students drank to
      intoxication the last time they went to each setting. RESULTS: Significant
      reductions in the incidence and likelihood of intoxication at off-campus parties
      and bars/restaurants were observed for Safer intervention universities compared
      to controls. A lower likelihood of intoxication was observed also for Safer
      intervention universities the last time students drank at an off-campus party
      (OR=0.81, 95% CI=0.68, 0.97); a bar or restaurant (OR=0.76, 95% CI=0.62, 0.94);
      or any setting (OR=0.80, 95% CI=0.65, 0.97). No increase in intoxication (e.g.,
      displacement) appeared in other settings. Further, stronger intervention effects
      were achieved at Safer universities with the highest level of implementation.
      CONCLUSIONS: Environmental prevention strategies targeting settings where the
      majority of heavy drinking events occur appear to be effective in reducing the
      incidence and likelihood of intoxication among college students.

PMID- 21084069
TI  - Evidence for truth(r): the young adult response to a youth-focused anti-smoking
      media campaign.
AB  - BACKGROUND: Previous studies have shown that exposure to truth(r) and similar
      countermarketing campaigns is associated with an increase in anti-smoking
      attitudes and beliefs in those aged 12-17 years and a decrease in youth smoking.
      However, it is unclear how such campaigns influence young adults aged 18-24
      years. PURPOSE: To examine levels of awareness and the effect of the national
      truth campaign on smoking-related attitudes, beliefs, and intentions in young
      adults. METHODS: Data on respondents, aged 18-24 years, from the Legacy Media
      Tracking Surveys-eight cross-sectional nationally representative telephone
      surveys administered from 2000 to 2004-were combined and analyzed in 2009.
      Logistic regression analyses were used to examine the associations between
      confirmed awareness of the truth campaign and smoking-related attitudes, beliefs,
      and intentions. A second set of models was used to examine the association of
      attitudes and beliefs targeted by the campaign with smoking intentions. RESULTS:
      A majority of young adults showed confirmed awareness of the truth campaign.
      Awareness was associated with roughly half of the anti-smoking attitudes and
      beliefs, and it was associated marginally with the intention to quit among
      smokers (p=0.06). Several of the attitudes and beliefs targeted by the campaign
      were associated with the intention to not smoke (among nonsmokers) and to quit
      (among smokers). CONCLUSIONS: Messages contained in youth-focused anti-smoking
      campaigns may promote attitudinal and behavioral change in young adults. Young
      adults are at risk for both initiation and establishment of smoking, while also
      being targeted specifically by the tobacco industry, so it is critical to
      consider this audience when developing and implementing anti-smoking
      interventions.

PMID- 21084071
TI  - Housing affordability and health among homeowners and renters.
AB  - BACKGROUND: Although lack of affordable housing is common in the U.S., few
      studies have examined the association between housing affordability and health.
      PURPOSE: Using quasi-experimental methods, the aim of this study was to examine
      whether housing affordability is linked to a number of important health outcomes,
      controlling for perceptions of neighborhood quality, and determining whether this
      association differs by housing tenure (renting versus owning). METHODS: Data from
      the 2008 Southeastern Pennsylvania Household Health Survey, a telephone-based
      survey of 10,004 residents of Philadelphia and its four surrounding counties,
      were analyzed. The association between housing affordability and health outcomes
      was assessed using propensity score methods to compare individuals who reported
      living in unaffordable housing situations to similar individuals living in
      affordable ones. RESULTS: Overall, 48.4% reported difficulty paying housing
      costs. People living in unaffordable housing had increased odds of poor self
      rated health (AOR=1.75, 95% CI=1.33, 2.29); hypertension (AOR=1.34, 95% CI=1.07,
      1.69); arthritis (AOR=1.92, 95% CI=1.56, 2.35); cost-related healthcare
      nonadherence (AOR=2.94, 95% CI=2.04, 4.25); and cost-related prescription
      nonadherence (AOR=2.68, 95% CI=1.95, 3.70). There were no significant
      associations between housing affordability and heart disease, diabetes, asthma,
      psychiatric conditions, being uninsured, emergency department visits in the past
      year, obesity, and being a current smoker. Renting rather than owning a home
      heightened the association between unaffordable housing and self-rated health
      (AOR=2.55, 95% CI=1.93, 3.37 for renters and not significant among homeowners)
      and cost-related healthcare nonadherence (AOR=4.74, 95% CI=3.05, 7.35 for renters
      and AOR=1.99, 95% CI=1.15, 3.46 for homeowners). CONCLUSIONS: The financial
      strain of unaffordable housing is associated with trade-offs that may harm
      health. Programs that target housing affordability for both renters and
      homeowners may be an important means for improving health.

PMID- 21084070
TI  - Adolescent smoking: effect of school and community characteristics.
AB  - BACKGROUND: A substantial challenge in addressing adolescent tobacco use is that
      smoking behaviors occur in complex environments that involve the school setting
      and larger community context. PURPOSE: This study provides an integrated
      description of factors from the school and community environment that affect
      youth smoking and explains variation in individual smoking behaviors both within
      and across schools/communities. METHODS: Data were collected from 82 randomly
      sampled secondary schools in five Canadian provinces (British Columbia, Manitoba,
      Ontario, Quebec, Newfoundland, and Labrador) during the 2003-2004 school year.
      Cross-sectional data were obtained from students; school administrators (school
      based tobacco control policies and programs); and from observations in the
      community. In 2009, hierarchic logistic regression was used to model the role of
      individual, school, and community variables in predicting student smoking
      outcomes. RESULTS: Students who attended a school with a focus on tobacco
      prevention (OR=0.87, 95% CI=0.81, 0.94) and stronger policies prohibiting tobacco
      use (OR=0.92, 95% CI=0.88, 0.97) were less likely to smoke than students who
      attended a school without these characteristics. A student was more likely to
      smoke if a greater number of students smoked on the school periphery (OR=1.25,
      95% CI=1.07, 1.47). Within the community, price per cigarette (OR=0.91, 95%
      CI=0.84, 0.99) and immigrants (OR=0.99, 95% CI=0.98, 0.99) were inversely related
      to students' smoking status. CONCLUSIONS: The results suggest that school and
      community characteristics account for variation in smoking levels across schools.
      Based on the current findings, the ideal school setting that supports low student
      smoking levels is located in a neighborhood where the cost of cigarettes is high,
      provides tobacco prevention education, and has a policy prohibiting smoking.

PMID- 21084072
TI  - U.S. child death review programs: assessing progress toward a standard review
      process.
AB  - BACKGROUND: Child death review (CDR) programs examine the circumstances of
      children's deaths to gain information on how and why children die for the purpose
      of promoting the health, safety, and protection of children. PURPOSE: The purpose
      of this study was to conduct a systematic review of the 50 states and District of
      Columbia CDR programs, with specific focus on the use of standardized procedures
      and best-practice recommendations. This included assessment of which deaths are
      reviewed, the model of review, team membership, and standardization of data
      collection and reporting. METHODS: Data were collected through semistructured
      phone interviews with representatives of the 50 states and District of Columbia
      CDR programs and online sources. Data collection and analyses were conducted in
      2009. RESULTS: Forty-eight states and the District of Columbia have active CDR
      programs at the state and/or local level, and the majority use a national data
      collection system. However, results revealed numerous inconsistencies across
      programs in policies, procedures, and data collection. CONCLUSIONS: This study
      reflects the minimal progress that has been made in the CDR process in the U.S.
      since the last systematic review of the programs in 2001. The study documents
      substantial discrepancies among the U.S. CDR programs, affecting the consistency
      of data obtained by individual states and, ultimately, prevention efforts at the
      national level. Information from this review can inform CDR programs as they
      develop and refine procedures and guide future research on the effectiveness and
      limitations of variations in procedures.

PMID- 21084073
TI  - Abuse in childhood and adolescence as a predictor of type 2 diabetes in adult
      women.
AB  - BACKGROUND: Although child abuse is associated with obesity, it is not known
      whether early abuse increases risk of type 2 diabetes. PURPOSE: To investigate
      associations of child and adolescent abuse with adult diabetes. METHODS:
      Proportional hazards models were used to examine associations of lifetime abuse
      reported in 2001 with risk of diabetes from 1989 to 2005 among 67,853 women in
      the Nurses' Health Study II. Data were analyzed in 2009. RESULTS: Child or teen
      physical abuse was reported by 54% and sexual abuse by 34% of participants.
      Models were adjusted for age, race, body type at age 5 years, and parental
      education and history of diabetes. Compared to women who reported no physical
      abuse, the hazards ratio (HR) was 1.03 (95% CI=0.91, 1.17) for mild physical
      abuse; 1.26 (1.14, 1.40) for moderate physical abuse; and 1.54 (1.34, 1.77) for
      severe physical abuse. Compared with women reporting no sexual abuse in childhood
      or adolescence, the HR was 1.16 (95% CI=1.05, 1.29) for unwanted sexual touching;
      1.34 (1.13, 1.59) for one episode of forced sexual activity; and 1.69 (1.45,
      1.97) for repeated forced sex. Adult BMI accounted for 60% (95% CI=32%, 87%) of
      the association of child and adolescent physical abuse and 64% (95% CI=38%, 91%)
      of the association of sexual abuse with diabetes. CONCLUSIONS: Moderate to severe
      physical and sexual abuse in childhood and adolescence have dose-response
      associations with risk of type 2 diabetes among adult women. This excess risk is
      partially explained by the higher BMI of women with a history of early abuse.

PMID- 21084074
TI  - Active living for rural children: community perspectives using PhotoVOICE.
AB  - BACKGROUND: Active living integrates physical activity into one's daily routine.
      Current understanding of active living among children and their families living
      in rural communities is limited. A community perspective is critical to
      understand the contextual factors that influence children's physical activity in
      rural areas. PURPOSE: The purpose of this study was to identify the perceived
      environmental factors that support or hinder physical activity among rural
      children to develop testable hypotheses to inform future interventions for
      reducing unhealthy weight gain and preventing chronic diseases associated with
      physical inactivity. METHODS: PhotoVOICE was used to explore active living
      opportunities and barriers for children living in four low-income, rural U.S.
      communities. In 2007, parents (n=99) and elementary school staff (n=17) received
      disposable cameras to document their perspective. Using their photographs and
      narratives, participants developed emergent themes during a facilitated group
      discussion. In 2008, study authors used the Analysis Grid for Environments Linked
      to Obesity (ANGELO) framework to categorize the themes. RESULTS: Microenvironment
      themes include physical (e.g., natural features, topography); sociocultural
      (e.g., isolation); policy (e.g., time for school recess); and economic (e.g.,
      funding for physical activity programs). Macroenvironmental themes related to the
      built and natural environments and transportation infrastructure. CONCLUSIONS:
      This study identified rural environment elements that community members perceived
      as influencing children's physical activity patterns. Certain aspects were unique
      to rural areas, whereas other urban and suburban factors may be generalizable to
      rural settings. PhotoVOICE was a useful participatory research method to gain
      insight into perceived factors affecting rural children's physical activity
      behaviors.

PMID- 21084076
TI  - Adoption of health promotion practices in a cohort of U.S. physician
      organizations.
AB  - BACKGROUND: Physician organizations such as medical groups and independent
      practice associations can play a vital role in health promotion through the
      adoption of effective health promotion practices such as health risk assessments,
      patient reminder systems, and health promotion education programs. PURPOSE: To
      examine organizational changes in a cohort of physician organizations and
      changing health promotion practices. METHODS: Data for a cohort of 369 physician
      organizations in the U.S. with 20 or more physicians were collected between
      September 2000 and September 2001 and subsequently from March 2006 to March 2007.
      Paired-sample t tests were used to identify changes in physician organization
      characteristics and the use of nine health promotion practices between 2000-2001
      and 2006-2007. RESULTS: Compared to 2000-2001, the cohort of physician
      organizations in 2006-2007 was larger, more likely to be owned by physicians;
      less likely to be owned by a hospital, health system, or HMO; more profitable;
      and more likely to use electronic information technology. Between 2000-2001 and
      2006-2007, physician organizations increased the use of health risk appraisals to
      contact high-risk patients and increased the use of reminders for eye exams for
      diabetic patients. During the same time period, physician organizations decreased
      the use of nutrition and weight-loss health promotion programs. CONCLUSIONS: The
      adding and dropping of programs among physician organizations is due to many
      factors, including changing regulatory environments, market conditions,
      populations, and new health promotion technologies. In the coming years,
      incentives and regulatory policy should encourage the adoption of effective
      health promotion practices by physician organizations.

PMID- 21084075
TI  - Prevalence and predictors of weight-loss maintenance in a biracial cohort:
      results from the coronary artery risk development in young adults study.
AB  - BACKGROUND: Few population-based studies have examined the behavioral and
      psychosocial predictors of long-term weight-loss maintenance. PURPOSE: The goal
      of this study was to determine the prevalence and predictors of weight-loss
      maintenance in a biracial cohort of younger adults. METHODS: This study examined
      a population-based sample of overweight/obese African-American and white men and
      women who had >= 5% weight loss between 1995 and 2000. Subsequent changes in
      weight, physical activity, and behavioral and psychosocial factors were examined
      between 2000 and 2005. Analyses were conducted in 2008-2009. RESULTS: Among the
      1869 overweight/obese individuals without major disease in 1995, a total of 536
      (29%) lost >= 5% between 1995 and 2000. Among those who lost weight, 34% (n=180)
      maintained at least 75% of their weight loss between 2000 and 2005, whereas 66%
      subsequently regained. Higher odds of successful weight-loss maintenance were
      related to African-American race (OR=1.7, p=0.03); smoking (OR=3.4, p=0.0001);
      history of diabetes (OR=2.2, p=0.04); increases in moderate physical activity
      between 2000 and 2005 (OR=1.4, p=0.005); increases in emotional support over the
      same period (OR=1.6, p=0.01); and less sugar-sweetened soft drink consumption in
      2005 (OR=0.8, p=0.006). CONCLUSIONS: One third of overweight men and women who
      lost weight were able to maintain 75% or more of their weight loss over 5 years.
      Interventions to promote weight-loss maintenance may benefit from targeting
      increased physical activity and emotional support and decreased sugar-sweetened
      soft drink consumption.

PMID- 21084077
TI  - Human papillomavirus vaccine among adult women: disparities in awareness and
      acceptance.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccines have been shown to be safe and
      highly effective in young and middle-aged women. PURPOSE: This study aimed to
      assess vaccine awareness and desire for vaccination among adult women aged 18-55
      years residing in Los Angeles County CA. METHODS: This study is nested in the
      2007 Los Angeles County Health Survey. Included in the analyses were 2295 women
      aged 18-55 years. Logistic regression was used to evaluate vaccine awareness and
      intention to become vaccinated in association with various factors. All analyses
      employed weighted data and were conducted in 2009. RESULTS: Only 5% of women aged
      18-26 years had received the HPV vaccine in its first year on the market.
      Overall, 67% of women aged 18-55 years had heard of the vaccine. Among those who
      knew of the vaccine but had not received it, 61% reported they were likely to
      receive the vaccine. Latina, black, and Asian/Pacific Islander women were only
      half as likely to have heard of the vaccine as white women, but Latinas and
      Asian/Pacific Islander women were more willing to be vaccinated than white or
      black women. Education was associated positively with awareness, but inversely
      associated with intention to be vaccinated. Awareness and desire for vaccination
      also varied substantially by other factors such as language spoken at home.
      CONCLUSIONS: This population-based study of diverse women reveals important
      disparities in HPV vaccine awareness and intention to be vaccinated. Culturally
      and linguistically competent educational campaigns about HPV immunization are
      warranted, and should target high-risk populations.

PMID- 21084078
TI  - Smoking-cessation interventions for U.S. young adults: a systematic review.
AB  - CONTEXT: Studies have demonstrated the importance of quitting smoking before age
      30 years to avoid tobacco-related mortality but little attention has been paid to
      developing evidence-based smoking-cessation interventions for young adults, as
      distinct from adolescents and older-aged adults. The objective of this study was
      to conduct a systematic review of smoking-cessation interventions for U.S. young
      adults (aged 18-24 years). EVIDENCE ACQUISITION: Electronic searches were
      conducted in CINAHL, the Cochrane Library, EMBASE, PsycINFO, PubMed, Scopus, and
      Sociological Abstracts to identify eligible interventions through August 31,
      2009. Two independent coders critically evaluated the methodology and findings of
      all retrieved articles. Data analysis was conducted in 2010. EVIDENCE SYNTHESIS:
      Twelve RCTs and two nonrandomized studies met the inclusion criteria; these
      studies varied with respect to sample size, intervention, outcomes assessed, and
      smoking measures. Pooled results for two studies based on social cognitive theory
      indicated that they were effective in promoting short-term abstinence at 1-3
      month follow-up and 4-6-month follow-up. Four studies had a significant positive
      impact on smoking cessation: two in the short term and two at 6 months or more.
      CONCLUSIONS: There is limited evidence demonstrating efficacy of smoking
      cessation interventions for U.S. young adults. There were no pharmacologic
      interventions included in this review. Promising interventions were brief, with
      extended support via telephone and electronic media. Further high-quality studies
      using standardized smoking measures and additional studies outside the college
      setting are needed to identify and tailor effective smoking-cessation
      interventions for at-risk young adults in the U.S.

PMID- 21084079
TI  - Effectiveness of policies maintaining or restricting days of alcohol sales on
      excessive alcohol consumption and related harms.
AB  - Local, state, and national laws and policies that limit the days of the week on
      which alcoholic beverages may be sold may be a means of reducing excessive
      alcohol consumption and related harms. The methods of the Guide to Community
      Preventive Services were used to synthesize scientific evidence on the
      effectiveness for preventing excessive alcohol consumption and related harms of
      laws and policies maintaining or reducing the days when alcoholic beverages may
      be sold. Outcomes assessed in 14 studies that met qualifying criteria were
      excessive alcohol consumption and alcohol-related harms, including motor vehicle
      injuries and deaths, violence-related and other injuries, and health conditions.
      Qualifying studies assessed the effects of changes in days of sale in both on
      premises settings (at which alcoholic beverages are consumed where purchased) and
      off-premises settings (at which alcoholic beverages may not be consumed where
      purchased). Eleven studies assessed the effects of adding days of sale, and three
      studies assessed the effects of imposing a ban on sales on a given weekend day.
      The evidence from these studies indicated that increasing days of sale leads to
      increases in excessive alcohol consumption and alcohol-related harms and that
      reducing the number of days that alcoholic beverages are sold generally decreases
      alcohol-related harms. Based on these findings, when the expansion of days of
      sale is being considered, laws and policies maintaining the number of days of the
      week that alcoholic beverages are sold at on- and off-premises outlets in local,
      state, and national jurisdictions are effective public health strategies for
      preventing excessive alcohol consumption and related harms.

PMID- 21084080
TI  - Effectiveness of policies restricting hours of alcohol sales in preventing
      excessive alcohol consumption and related harms.
AB  - Local, state, and national policies that limit the hours that alcoholic beverages
      may be available for sale might be a means of reducing excessive alcohol
      consumption and related harms. The methods of the Guide to Community Preventive
      Services were used to synthesize scientific evidence on the effectiveness of such
      policies. All of the studies included in this review assessed the effects of
      increasing hours of sale in on-premises settings (in which alcoholic beverages
      are consumed where purchased) in high-income nations. None of the studies was
      conducted in the U.S. The review team's initial assessment of this evidence
      suggested that changes of less than 2 hours were unlikely to significantly affect
      excessive alcohol consumption and related harms; to explore this hypothesis,
      studies assessing the effects of changing hours of sale by less than 2 hours and
      by 2 or more hours were assessed separately. There was sufficient evidence in ten
      qualifying studies to conclude that increasing hours of sale by 2 or more hours
      increases alcohol-related harms. Thus, disallowing extensions of hours of alcohol
      sales by 2 or more should be expected to prevent alcohol-related harms, while
      policies decreasing hours of sale by 2 hours or more at on-premises alcohol
      outlets may be an effective strategy for preventing alcohol-related harms. The
      evidence from six qualifying studies was insufficient to determine whether
      increasing hours of sale by less than 2 hours increases excessive alcohol
      consumption and related harms.

PMID- 21084081
TI  - Recommendations on maintaining limits on days and hours of sale of alcoholic
      beverages to prevent excessive alcohol consumption and related harms.

PMID- 21084082
TI  - Housing is health care.

PMID- 21084083
TI  - The kids will be all right (if they don't smoke).

PMID- 21084085
TI  - Prevalence of hypertensive disorders in a prenatal clinic in Zanzibar.

PMID- 21084086
TI  - Combining qualitative and quantitative research within mixed method research
      designs: a methodological review.
AB  - OBJECTIVES: It has been argued that mixed methods research can be useful in
      nursing and health science because of the complexity of the phenomena studied.
      However, the integration of qualitative and quantitative approaches continues to
      be one of much debate and there is a need for a rigorous framework for designing
      and interpreting mixed methods research. This paper explores the analytical
      approaches (i.e. parallel, concurrent or sequential) used in mixed methods
      studies within healthcare and exemplifies the use of triangulation as a
      methodological metaphor for drawing inferences from qualitative and quantitative
      findings originating from such analyses. DESIGN: This review of the literature
      used systematic principles in searching CINAHL, Medline and PsycINFO for
      healthcare research studies which employed a mixed methods approach and were
      published in the English language between January 1999 and September 2009.
      RESULTS: In total, 168 studies were included in the results. Most studies
      originated in the United States of America (USA), the United Kingdom (UK) and
      Canada. The analytic approach most widely used was parallel data analysis. A
      number of studies used sequential data analysis; far fewer studies employed
      concurrent data analysis. Very few of these studies clearly articulated the
      purpose for using a mixed methods design. The use of the methodological metaphor
      of triangulation on convergent, complementary, and divergent results from mixed
      methods studies is exemplified and an example of developing theory from such data
      is provided. CONCLUSION: A trend for conducting parallel data analysis on
      quantitative and qualitative data in mixed methods healthcare research has been
      identified in the studies included in this review. Using triangulation as a
      methodological metaphor can facilitate the integration of qualitative and
      quantitative findings, help researchers to clarify their theoretical propositions
      and the basis of their results. This can offer a better understanding of the
      links between theory and empirical findings, challenge theoretical assumptions
      and develop new theory.

PMID- 21084087
TI  - The impact of Nursing Rounds on the practice environment and nurse satisfaction
      in intensive care: pre-test post-test comparative study.
AB  - BACKGROUND: Factors previously shown to influence patient care include effective
      decision making, team work, evidence based practice, staffing and job
      satisfaction. Clinical rounds have the potential to optimise these factors and
      impact on patient outcomes, but use of this strategy by intensive care nurses has
      not been reported. OBJECTIVES: To determine the effect of implementing Nursing
      Rounds in the intensive care environment on patient care planning and nurses'
      perceptions of the practice environment and work satisfaction. DESIGN: Pre-test
      post-test 2 group comparative design. SETTINGS: Two intensive care units in
      tertiary teaching hospitals in Australia. PARTICIPANTS: A convenience sample of
      registered nurses (n=244) working full time or part time in the participating
      intensive care units. METHODS: Nurses in participating intensive care units were
      asked to complete the Practice Environment Scale-Nursing Work Index (PES-NWI) and
      the Nursing Worklife Satisfaction Scale (NWSS) prior to and after a 12 month
      period during which regular Nursing Rounds were conducted in the intervention
      unit. Issues raised during Nursing Rounds were described and categorised. The
      characteristics of the sample and scale scores were summarised with differences
      between pre and post scores analysed using t-tests for continuous variables and
      chi-square tests for categorical variables. Independent predictors of the PES-NWI
      were determined using multivariate linear regression. RESULTS: Nursing Rounds
      resulted in 577 changes being initiated for 171 patients reviewed; these changes
      related to the physical, psychological--individual, psychological--family, or
      professional practice aspects of care. Total PES-NWI and NWSS scores were similar
      before and after the study period in both participating units. The NWSS sub-scale
      of interaction between nurses improved in the intervention unit during the study
      period (pre--4.85+/-0.93; post--5.36+/-0.89, p=0.002) with no significant
      increase in the control group. Factors independently related to higher PES-NWI
      included intervention site and less years in critical care (p<0.05). CONCLUSIONS:
      Implementation of Nursing Rounds within the intensive care environment is
      feasible and is an effective strategy for initiating change to patient care.
      Application and testing of this strategy, including identification of the most
      appropriate methods of measuring impact, in other settings is needed to determine
      generalisability.

PMID- 21084089
TI  - Improved selectivity for the analysis of maternal serum and cord serum for
      polyfluoroalkyl chemicals.
AB  - Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid, two of the most
      widely studied polyfluoroalkyl chemicals (PFCs), can cross the placenta.
      Therefore, data on the exposure to PFCs of the very young are needed to evaluate
      the potential health effects associated with such exposure. Human serum,
      especially serum collected from pregnant women and cord serum, may contain
      endogenous components that can interfere in the separation by high performance
      liquid chromatography (HPLC) of PFOS and another PFC of interest, perfluorohexane
      sulfonic acid (PFHxS), from other serum biomolecules. The presence of such
      interferences may prevent the adequate quantification of PFOS and PFHxS in cord
      serum or serum collected from pregnant women, and potentially hinder the
      assessment of gestational exposure to these important PFCs using biomonitoring.
      We have modified our on-line solid phase extraction-HPLC-isotope dilution-tandem
      mass spectrometry analytical method for measuring PFCs in serum and developed an
      approach that allows for the elimination of these potential interferences without
      compromising analytical sensitivity and throughput. The combination of
      acetonitrile as the HPLC mobile phase organic solvent and a Betasil C8 HPLC
      column provided the best separation of PFOS and PFHxS from interferent peaks. In
      addition to eliminating these interferences, the acetonitrile method has a
      shorter runtime and is more sensitive for most PFCs (limits of detection were 0.1
      ng/mL except for PFOS (0.2 ng/mL)) than our previous method that used methanol
      for the HPLC separation. The present method should improve the precise and
      selective analysis of maternal and cord serum for PFCs.

PMID- 21084088
TI  - The inhibitory FcgammaRIIb modulates the inflammatory response and influences
      atherosclerosis in male apoE(-/-) mice.
AB  - BACKGROUND: Atherosclerosis is widely accepted as an inflammatory disease
      involving both innate and adaptive immunity. B cells and/or antibodies have
      previously been shown to play a protective role against atherosclerosis. Aside
      from their ability to bind to antigens, antibodies can influence inflammatory
      responses by interacting with various Fcgamma receptors on the surface of antigen
      presenting cells. Although studies in mice have determined that stimulatory
      Fcgamma receptors contribute to atherosclerosis, the role of the inhibitory
      Fcgamma receptor IIb (FcgammaRIIb) has only recently been investigated. METHODS
      AND RESULTS: To determine the importance of FcgammaRIIb in modulating the
      adaptive immune response to hyperlipidemia, we generated FcgammaRIIb-deficient
      mice on the apoE-deficient background (apoE/FcgammaRIIb(-/-)). We report that
      male apoE/FcgammaRIIb(-/-) mice develop exacerbated atherosclerosis that is
      independent of lipid levels, and is characterized by increased antibody titers to
      modified LDL and pro-inflammatory cytokines in the aorta. CONCLUSIONS: These
      findings suggest that antibodies against atherosclerosis-associated antigens
      partially protect against atherosclerosis in male apoE(-/-) mice by conveying
      inhibitory signals through the FcgammaRIIb that downregulate pro-inflammatory
      signaling via other immune receptors. These data are the first to describe a
      significant in vivo effect for FcgammaRIIb in modulating the cytokine response in
      the aorta in male apoE(-/-) mice.

PMID- 21084090
TI  - Determination of phosphine and other fumigants in air samples by thermal
      desorption and 2D heart-cutting gas chromatography with synchronous SIM/Scan mass
      spectrometry and flame photometric detection.
AB  - Fumigants and volatile industrial chemicals are particularly hazardous to health
      when a freight container is fumigated or the contaminated material is introduced
      into its enclosed environment. Phosphine is now increasingly used as a fumigant,
      after bromomethane--the former fumigant of choice--has been banned by the
      Montreal Protocol. We have enhanced our previously established thermal desorption
      gas chromatography-mass spectrometry (TD-GC-MS) method by integrating a second
      gas chromatographic dimension and a flame photometric detector to allow the
      simultaneous detection of phosphine and volatile organic compounds (VOCs),
      providing a novel application. A thermal desorption system is coupled to a two
      dimensional gas chromatograph using both mass spectrometric and flame photometric
      detection (TD-2D-GC-MS/FPD). Additionally, the collection of mass spectrometric
      SIM and Scan data has been synchronised, so only a single analysis is now
      sufficient for qualitative scanning of the whole sample and for sensitive
      quantification. Though detection limits for the herewith described method are
      slightly higher than in the previous method, they are in the low MUL m(-3) range,
      which is not only below the respective occupational exposure and intervention
      limits but also allows the detection of residual contamination after ventilation.
      The method was developed for the separation and identification of 44 volatile
      substances. For 12 of these compounds (bromomethane, iodomethane,
      dichloromethane, 1,2-dichlorethane, benzene, tetrachloromethane, 1,2
      dichloropropane, toluene, trichloronitromethane, ethyl benzene, phosphine, carbon
      disulfide) the method was validated as we chose the target compounds due to their
      relevance in freight container handling.

PMID- 21084091
TI  - Size-exclusion separation of proteins using a biocompatible polymeric monolithic
      capillary column with mesoporosity.
AB  - Biocompatible poly(ethylene glycol methyl ether acrylate-co-polyethylene glycol
      diacrylate) monoliths were prepared for size exclusion chromatography (SEC) of
      proteins in the capillary format using Brij 58P in a mixture of hexanes and
      dodecanol as porogens. The monolithic columns provided size separation of four
      proteins in 20 mM sodium phosphate buffer (pH 7.0) containing 0.15 M NaCl, and
      there was a linear relationship between the retention times and the logarithmic
      values of the molecular weights. Compared to SEC monoliths previously synthesized
      using a triblock copolymer of polyethylene oxide and polypropylene oxide, an
      increase in mesoporosity was confirmed by inverse size exclusion chromatography.
      As a result, improved protein separation in the high molecular weight range and
      reduced column back-pressure were observed.

PMID- 21084092
TI  - Gas bubbles in simulation and experiment.
AB  - An experimental setup for the examination of single bubbles, rising in a liquid,
      is presented. Its main part is a rotating chamber, in which the bubble is
      spatially stabilized by a balance of buoyancy, drag, and lift forces. This allows
      for long observation periods in time. Experimental results are presented for air
      bubbles in silicone oil. The experimental results are validated by a comparison
      with numerical simulations. A modified, mass-conserving level-set method is used
      for the representation of the free interface, while an immersed-boundary
      formulation is engaged for the conservation equations. The agreement between
      experiment and simulation, and to available correlations from literature, is
      found to be perfect. It is shown that the influence of the liquid shear due to
      the rotation is negligible. Also, for the presented liquid system, no influence
      by Marangoni stresses could be found, which makes the system of air and silicone
      oil a good choice for validation purposes.

PMID- 21084093
TI  - Synthesis and antibacterial activity of copper-immobilized membrane comprising
      grafted poly(4-vinylpyridine) chains.
AB  - Poly(4-vinylpyridine) (P4VP) brushes were grafted onto microporous polysulfone
      (PSF) membranes via surface-initiated atom transfer radical polymerization (SI
      ATRP) and then immobilized copper (II) ions on the modified membrane. Copper
      loaded membranes exhibited excellent antibacterial properties with the added
      advantage of repeated use. The chemical composition and surface morphology of the
      functionalized membrane was characterized by ATR-FTIR, XPS, SEM, and AFM. The
      results showed that P4VP brushes clustered to rod-shaped covering and the sub
      layer of membrane maintained sponge-like structures at the same time.
      Additionally, the kinetic study of SI-ATRP reaction revealed that the chain
      length of P4VP brushes increased linearly as the polymerization time increased.
      The antibacterial effects of copper-loaded CMPSF-g-P4VP membrane against
      Escherichiacoli were examined and the antibacterial efficiency reached 100% when
      2.49wt.% of copper (II) ions was immobilized on membrane. The presented results
      could serve as a good starting point for the fabrication of antibacterial CMPSF
      membranes for waste-water treatment applications.

PMID- 21084094
TI  - Understanding surfactant aided aqueous dispersion of multi-walled carbon
      nanotubes.
AB  - Dispersions of multi-walled carbon nanotubes (MWNTs) assisted by surfactant
      adsorption were prepared for a number of ionic and non-ionic surfactants
      including sodium 4-dodecylbenzenesulfonate (NaDDBS), hexadecyl(trimethyl)azanium
      bromide (CTAB), sodium dodecane-1-sulfonate (SDS), Pluronic(r) F68, Pluronic(r)
      F127, and Triton(r) X-100 to examine the effects of nanotube diameter, surfactant
      concentration, and pH on nanotube dispersability. Nanotube diameter was found to
      be an important role in surfactant adsorption rendering single-walled carbon
      nanotube studies as unreliable in predicting MWNT dispersive behavior. Similar to
      other reports, increasing surfactant concentrations resulted in a solubility
      plateau. Quantification of nanotube solubility at these plateaus demonstrated
      that CTAB is the best surfactant for MWNTs at neutral pH conditions. Deviations
      from neutral pH demonstrated negligible influence on non-ionic surfactant
      adsorption. In contrast, both cationic and anionic surfactants were found to be
      poor dispersing aids for highly acidic solutions while, CTAB remained a good
      surfactant under strongly basic conditions. These pH dependent results were
      explained in the context of nanotube surface ionization and Debye length
      variation.

PMID- 21084095
TI  - Highly water-soluble nanocrystal powders of magnetite and maghemite coated with
      gluconic acid: Preparation, structure characterization, and surface coordination.
AB  - A simple method was developed to prepare highly water-soluble nanocrystal powders
      of magnetic iron oxides with different oxidation degree from magnetite
      (Fe(3)O(4)) to maghemite (gamma-Fe(2)O(3)) coated with gluconic acid (GLA). X-ray
      diffraction and transmission electron microscopy measurements show that the
      products have a narrow size distribution, and the cores are inverse spinel iron
      oxides and completely crystallized. Vibrating sample magnetometry measurements
      reveal that all the samples exhibit superparamagnetic behavior at room
      temperature. Fourier transform infrared (FTIR) and Raman spectra were used to
      identify the products. It is shown that GLA molecules are immobilized on the
      nanoparticle surface by chemical bonding and the carboxyl is asymmetrically bound
      to the surface iron atom, and the vacancies in the gamma-Fe(2)O(3) cores are
      disordered. Compared with FTIR, Raman spectrum analysis is a rapid, simple, and
      accurate method for identifying inverse spinel iron oxides. The chemical
      stability and the high solubility of the products are explained in terms of the
      proposed coordination modes of the surface iron atom with GLA.

PMID- 21084096
TI  - On the flocculation and re-dissolution of trivalent lanthanide metal ions by
      sodium dodecyl sulfate in aqueous solutions.
AB  - The interaction between aqueous solutions of trivalent lanthanide ions (M(3+):
      La(III) and Gd(III) and Tb (III)) at fixed (1mM) concentrations and various
      concentrations of sodium dodecyl sulfate (SDS), ranging from pre- to post
      micellar, has been investigated by ICP-AES (La(III) and Gd(III)), luminescence
      spectra (Gd(III)) and lifetimes (Tb(III)) and (139)La NMR spectroscopy. It has
      been found that at concentration ratios, r=[SDS]/[M(3+)], around the charge
      neutralization value (ca. 3), dodecyl sulfate (DS(-)) anion interacts with the
      metal ions to form insoluble aggregates. The metal ion-DS(-) complexes remain
      flocculated for r values below 5-6 (Gd(III) and La(III), respectively), while at
      higher r values, re-dissolution takes place. The flocculated aggregates have been
      characterized by X-ray powder diffraction, and show a lamellar structure. Job
      plot method indicates that a complex with a 1:3 (M(3+):DS(-)) stoichiometry is
      formed. From ICP-AES analysis, a model based on a three-step mechanism has been
      developed and association constants calculated. For all systems the interaction
      between DS(-) and metal ions follows an associative process with K values ranging
      between K(1)=10 and K(3)=10(4). These data are discussed on the basis of the
      physical-chemical characteristics of the metal ions. Re-dissolution with
      increasing surfactant concentration is attributed to formation of mixed
      lanthanide/sodium dodecyl sulfate aggregates, with the relative lanthanide
      fraction in these species decreasing with increasing SDS concentration.

PMID- 21084097
TI  - Synthesis and physical properties of new surfactants based on ionic liquids:
      Improvement of thermal stability and mechanical behaviour of high density
      polyethylene nanocomposites.
AB  - Ionic liquids based on alkyltriphenyl phosphonium and dialkyl imidazolium cations
      with long alkyl chains have been synthesized and used as new surfactants for
      cationic exchange of layered silicates. The influence of the alkyl chain length
      and the chemical nature of the conteranion or of the cation on the thermal
      stability of these new intercalating agents and on imidazolium- (MMT-I) or
      phosphonium- (MMT-P) modified montmorillonites have been analyzed by
      thermogravimetric analysis (TGA). Thermoplastic nanocomposites based on these
      modified montmorillonites with a very low amount of nanofillers (1wt.%) have been
      processed by melt mixing using a twin screw extruder. The distribution of the
      clay layers in a high density polyethylene (HDPE) matrix was characterized and
      finally the mechanical and thermal properties of the corresponding nanocomposites
      were determined.

PMID- 21084098
TI  - Immunohistochemical characterization of oral mucosal lesions in cats with chronic
      gingivostomatitis.
AB  - Histological and immunohistochemical studies were performed on samples of the
      glossopalatine mucosa from 30 cats with feline chronic gingivostomatitis (FCGS).
      Immunohistochemical labelling and computer-assisted morphometric analysis were
      used to identify expression of CD3, CD4, CD8, CD79a, IgG, IgM, IgA, leucocyte
      antigen 1 (L1) and class II molecules of the major histocompatibility complex
      (MHC) in tissue sections. Mast cells were detected by toluidine blue staining.
      The microscopical lesions were graded by severity of inflammation and although
      this grading correlated significantly with the severity of mucosal inflammation
      assessed at clinical examination, sites assessed as clinically normal or mildly
      inflamed were poorly predictive of the histopathological grade in the
      corresponding tissue sample. The number of CD79a+ cells (mostly plasma cells),
      L1+ cells (mostly neutrophils) and CD3+ T cells, and the level of MHC class II
      expression, tended to correlate with the severity of the inflammation. In
      general, CD8+ T cells were more numerous than CD4+ T cells. The majority of the
      plasma cells were of the IgG isotype and fewer IgA+ and IgM+ plasma cells were
      present. In some cases MHC class II expression by mucosal epithelium, salivary
      duct epithelium or skeletal muscle fibres was observed. Relative to equivalent
      oral mucosal samples from healthy cats, the number of cells labelled for CD3,
      CD4, CD8, CD79a, IgG, IgM, IgA or L1, and the number of mast cells, within the
      lamina propria/submucosa were significantly increased. Limited analysis of the
      epithelial compartment also found more CD3+ T cells compared with healthy cats.
      These findings indicate that the glossopalatine mucosal lesions in FCGS represent
      a complex, chronic and destructive inflammatory process affecting the epithelium
      and lamina propria, with frequent extension into submucosal tissues. The
      predominance of CD8+ cells over CD4+ cells suggests the induction of an
      underlying cytotoxic cell-mediated immune response, which could be consistent
      with a viral aetiology.

PMID- 21084099
TI  - FALS with Gly72Ser mutation in SOD1 gene: report of a family including the first
      autopsy case.
AB  - Clinical information on familial amyotrophic lateral sclerosis (FALS) with
      Gly72Ser mutation in the Cu/Zn superoxide dismutase-1 (SOD1) gene has been
      limited and autopsy findings remain to be clarified. We describe one Japanese
      family with ALS carrying Gly72Ser mutation in the SOD1 gene, in which autopsy was
      performed on one affected member. The autopsied female patient developed muscle
      weakness of the left thigh at age 66 and showed transient upper motor neuron
      signs. She died of respiratory failure 13 months after onset without artificial
      respiratory support. There were no symptoms suggesting bladder or rectal
      dysfunction throughout the clinical course. Her brother with ALS was shown to
      have Gly72Ser mutation in the SOD1 gene. Histopathologically, motor neurons were
      markedly decreased throughout the whole spinal cord, whereas corticospinal tract
      involvement was very mild and was demonstrated only by CD68 immunohistochemistry.
      Degeneration was evident in the posterior funiculus, Clarke's nucleus, posterior
      cerebellar tract, and Onuf's nucleus. Neuronal hyaline inclusions were rarely
      observed in the neurons of the spinal cord anterior horn including Onuf's
      nucleus, and were immunoreactive for SOD1. To date, neuron loss in Onuf's nucleus
      has hardly been seen in ALS, except in the patients showing prolonged disease
      duration with artificial respiratory support. Involvement of Onuf's nucleus may
      be a characteristic pathological feature in FALS with Gly72Ser mutation in the
      SOD1 gene.

PMID- 21084101
TI  - Thrombolysis in ischemic stroke patients with prior subtherapeutic warfarin use.

PMID- 21084102
TI  - Kinetic mechanism and product characterization of the enzymatic peroxidation of
      pterostilbene as model of the detoxification process of stilbene-type
      phytoalexins.
AB  - The enzymatic peroxidation of pterostilbene, a strong antifungal belonging to the
      stilbene family, by peroxidase (POX), is reported for the first time as a model
      of phytoalexin detoxification carried out by the enzymatic pool of pathogens.
      Kinetic characterization of the pterostilbene oxidation reaction pointed to an
      optimum pH of 7.0, at which value the thermal stability of POX was studied.
      Moreover, the data showed that pterostilbene inhibits POX activity at high
      concentrations of substrate. Several kinetic parameters, including V(max), K(m)
      and K(I), were calculated and values of 0.16DeltaAbs min(-1), 14.61 MUM, and
      31.41 MUM were reported. To understand the possible physiological role of this
      reaction in the phytoalexin detoxification process, the products of pterostilbene
      oxidation were identified using HPLC-MS and a radical-radical coupling reaction
      mechanism was proposed. Three main products with a high molecular weight and
      pronounced hydrophobicity were identified: pterostilbene cis dehydromer,
      pterostilbene trans dehydromer and pterostilbene open dimer. The dimeric
      structures of these molecules indicate that the pterostilbene oxidation reaction
      took place at the 4'-OH position of the hydroxystilbenic moieties and the three
      above mentioned dimeric products were found, due to the ability of electron
      delocalized radicals to couple at various sites. Finally, the capacity of
      cyclodextrins (CDs) as starch model molecules in plants to complex both the
      substrate and the products of the oxidation reaction was evaluated. The
      inhibition process of POX activity was modified at high pterostilbene
      concentrations due to sequestering of the substrate reaction and to the different
      affinity of the reaction products for CDs.

PMID- 21084103
TI  - Quantitative proteomic analyses of crop seedlings subjected to stress conditions;
      a commentary.
AB  - Quantitative proteomics is one of the analytical approaches used to clarify crop
      responses to stress conditions. Recent remarkable advances in proteomics
      technologies allow for the identification of a wider range of proteins than was
      previously possible. Current proteomic methods fall into roughly two categories:
      gel-based quantification methods, including conventional two-dimensional gel
      electrophoresis and two-dimensional fluorescence difference gel electrophoresis,
      and MS-based quantification methods consists of label-based and label-free
      protein quantification approaches. Although MS-based quantification methods have
      become mainstream in recent years, gel-based quantification methods are still
      useful for proteomic analyses. Previous studies examining crop responses to
      stress conditions reveal that each method has both advantages and disadvantages
      in regard to protein quantification in comparative proteomic analyses.
      Furthermore, one proteomics approach cannot be fully substituted by another
      technique. In this review, we discuss and highlight the basis and applications of
      quantitative proteomic analysis approaches in crop seedlings in response to
      flooding and osmotic stress as two environmental stresses.

PMID- 21084104
TI  - Human monoclonal antibodies to West Nile virus identify epitopes on the prM
      protein.
AB  - Hybridoma cell lines (2E8, 8G8 and 5G12) producing fully human monoclonal
      antibodies (hMAbs) specific for the pre-membrane (prM) protein of West Nile virus
      (WNV) were prepared using a human fusion partner cell line, MFP-2, and human
      peripheral blood lymphocytes from a blood donor diagnosed with WNV fever in 2004.
      Using site-directed mutagenesis of a WNV-like particle (VLP) we identified 4
      amino acid residues in the prM protein unique to WNV and important in the binding
      of these hMAbs to the VLP. Residues V19 and L33 are important epitopes for the
      binding of all three hMAbs. Mutations at residue, T20 and T24 affected the
      binding of hMAbs, 8G8 and 5G12 only. These hMAbs did not significantly protect
      AG129 interferon-deficient mice or Swiss Webster outbred mice from WNV infection.

PMID- 21084105
TI  - The lytic activation of KSHV during keratinocyte differentiation is dependent
      upon a suprabasal position, the loss of integrin engagement, and calcium, but not
      the interaction of cadherins.
AB  - We previously found that KSHV (HHV-8) lytic activation occurs during
      differentiation of oral keratinocytes in organotypic raft cultures. To further
      investigate the spatial and temporal aspects of KSHV lytic activation and the
      roles of integrins, cadherins, and calcium, we used rKSHV.219-infected primary
      oral keratinocytes in submerged, suspension, and direct suprabasal plating,
      models of differentiation. We found that early keratinocyte differentiation did
      not activate lytic KSHV in cells attached to a substratum, with activation only
      occurring in suprabasal cells. Temporally, KSHV lytic expression occurred between
      the expression of early and late differentiation markers. Keratinocytes
      differentiated in suspension culture, which mimics substratum loss that occurs
      with stratification, activated lytic KSHV. This lytic activation was inhibited by
      integrin engagement, showing that integrins are a control point for KSHV
      reactivation. A role for cadherins was not found. Elevated extracellular calcium
      was necessary, but not sufficient, for lytic activation.

PMID- 21084106
TI  - Interaction of factor VIII and von Willebrand factor and the identification of
      type 2N von Willebrand disease.

PMID- 21084107
TI  - Three-dimensional ultrasound for assessing women with gynecological cancer: a
      systematic review.
AB  - GOALS: Three-dimensional ultrasound (3D-US) is a new imaging technique that has
      become available in clinical practice. It is being increasingly used in women
      with gynecological cancer. The goal of this article is to review critically
      current evidence of the role of this technique in this clinical setting. METHODS:
      Through Medline search (2001-2010) 46 studies using 3D-US in women with
      gynecological cancer were identified (28 studies involving ovarian cancer, 15
      studies involving endometrial cancer and 6 studies involving cervical cancer). A
      systematic review of these studies was performed. RESULTS: Most studies were
      prospective and observational. Series were small in most of them. Ten studies
      addressed to technical and reproducibility issues. All of them demonstrate that
      3D-US is a reproducible technique among examiners. Studies involving ovarian
      cancer showed that gray-scale 3D-US is not superior to conventional 2D-US for
      predicting ovarian cancer. Tumor vascular assessment by 3D power Doppler showed
      that this method might be useful in a selected subset of adnexal masses. Studies
      involving endometrial cancer showed that endometrial volume estimation is more
      specific than endometrial thickness measurement for predicting endometrial
      cancer. This method is useful for determining myometrial infiltration in women
      with endometrial cancer. The role of 3D power Doppler in endometrial cancer is
      controversial. Studies involving cervical cancer showed that tumor vascularity as
      assessed by 3D power Doppler correlates with prognostic tumor features.
      CONCLUSIONS: Three-dimensional ultrasound is a new imaging technique that offers
      unique ways for assessing women with gynecologic cancer. Current evidence shows
      that it is reproducible. It might be useful in some clinical circumstances.
      Further studies are needed to establish its role in clinical practice in
      gynecologic oncology.

PMID- 21084108
TI  - Late GI and bladder toxicities after radiation for uterine cancer.
AB  - OBJECTIVE: To determine the impact of radiation treatment for corpus uteri cancer
      on the development of late gastrointestinal (GI) and bladder toxicities in older
      women. METHODS: We used a linked database of the Surveillance, Epidemiology and
      End Results (SEER) program tumor registry records and Medicare claims to estimate
      the risk of late radiation toxicities in a population based sample of 23,591
      women diagnosed with corpus uteri cancer from 1992 to 2005. Gastrointestinal (GI)
      and bladder diagnoses were included up to 60 months after diagnosis. Cox
      proportional hazard models were used to estimate risk of any late GI or bladder
      diagnosis with or without hospitalization, due to radiation. RESULTS: Women
      treated with radiation had an absolute increase in late GI toxicities of 7.7% and
      an absolute increase in late bladder toxicities of 3.9%. Most toxicities were not
      severe. Only 10% of irradiated women with a lower GI diagnosis and less than 1%
      of irradiated women with a bladder diagnosis, required hospitalization. In the
      multivariable analysis, advancing age, having chemotherapy, higher comorbidities
      and prior or early GI and bladder diagnoses were predictive of late toxicities
      among irradiated women. CONCLUSIONS: Late GI toxicities are more common than
      previously reported. It is important to analyze late toxicities in population
      based samples of women with uterine cancer. The results of this and future
      analyses can be used to identify areas where development of "survivorship plans"
      will remind and encourage women to report symptoms related to potential
      toxicities.

PMID- 21084109
TI  - Diffusion and concurrent solubility of self-adhering and new resin-matrix
      composites during water sorption/desorption cycles.
AB  - OBJECTIVES: To investigate the kinetic process of water diffusion and mass change
      in new resin-matrix composites during water sorption/desorption cycles. METHODS:
      Five new resin-matrix composites were investigated [Filtek((r)) Silorane (FS), GC
      Gradia Direct Anterior (GDA), GC Gradia Direct Posterior (GDP), GC Kalore (GCK),
      Vertise((r)) Flow (VF)]. Five disk-shaped specimens, per material (15.0+/-0.1) mm
      diameter by (2.0+/-0.1) mm, were prepared according to ISO 4049. Each disk was
      immersed separately in de-ionized water for 150 d and then reconditioned for 75
      d; all at (37+/-1) degrees C. Mass was measured at different time intervals.
      Perspex disks were used as control. Data analysis was done by repeated measures
      ANOVA, one-way ANOVA and Tukey's post hoc test (p<0.05). RESULTS: The water
      sorption (MUg/mm3) after 150 d immersion ranged from 13.51 MUg/mm3 (+/-0.40) for
      FS to 71.96 MUg/mm3 (+/-0.90) for VF. The solubility ranged up to 16.95 MUg/mm3
      (+/-0.79) for VF. A significant mass reduction occurred in VF after the peak
      value [73.63 MUg/mm3 (+/-0.31)] of water sorption was reached at 42 d. VF had the
      highest diffusion-coefficient for sorption: 5.23*10-9 cm2/s (+/-0.38) and
      desorption: 11.72*10-9 cm2/s (+/-0.16). Percentage sorption differences were
      significant for all materials (p<0.001), except between GCK and GDP. The early
      correlation between mass change and square root of time was linear. SIGNIFICANCE:
      Each resin-matrix composite varied in sorption/desorption cycles which may affect
      clinical service. A concurrent solubility process occurred during sorption of the
      self-adhering composite VF. The silorane composite FS exhibited minimal sorption.

PMID- 21084110
TI  - Pathogenic C difficile is here (and everywhere) to stay.

PMID- 21084113
TI  - Universal health coverage: friend or foe of health equity?

PMID- 21084112
TI  - Ebola haemorrhagic fever.
AB  - Ebola viruses are the causative agents of a severe form of viral haemorrhagic
      fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of
      central Africa. The exception is the species Reston Ebola virus, which has not
      been associated with human disease and is found in the Philippines. Ebola virus
      constitutes an important local public health threat in Africa, with a worldwide
      effect through imported infections and through the fear of misuse for biological
      terrorism. Ebola virus is thought to also have a detrimental effect on the great
      ape population in Africa. Case-fatality rates of the African species in man are
      as high as 90%, with no prophylaxis or treatment available. Ebola virus
      infections are characterised by immune suppression and a systemic inflammatory
      response that causes impairment of the vascular, coagulation, and immune systems,
      leading to multiorgan failure and shock, and thus, in some ways, resembling
      septic shock.

PMID- 21084114
TI  - The growing movement for universal health coverage.

PMID- 21084111
TI  - Clostridium difficile infection in Europe: a hospital-based survey.
AB  - BACKGROUND: Little is known about the extent of Clostridium difficile infection
      in Europe. Our aim was to obtain a more complete overview of C difficile
      infection in Europe and build capacity for diagnosis and surveillance. METHODS:
      We set up a network of 106 laboratories in 34 European countries. In November,
      2008, one to six hospitals per country, relative to population size, tested stool
      samples of patients with suspected C difficile infection or diarrhoea that
      developed 3 or more days after hospital admission. A case was defined when,
      subsequently, toxins were identified in stool samples. Detailed clinical data and
      stool isolates were collected for the first ten cases per hospital. After 3
      months, clinical data were followed up. FINDINGS: The incidence of C difficile
      infection varied across hospitals (weighted mean 4.1 per 10,000 patient-days per
      hospital, range 0.0-36.3). Detailed information was obtained for 509 patients.
      For 389 of these patients, isolates were available for characterisation. 65
      different PCR ribotypes were identified, of which 014/020 (61 patients [16%]),
      001 (37 [9%]), and 078 (31 [8%]) were the most prevalent. The prevalence of PCR
      ribotype 027 was 5%. Most patients had a previously identified risk profile of
      old age, comorbidity, and recent antibiotic use. At follow up, 101 (22%) of 455
      patients had died, and C difficile infection played a part in 40 (40%) of deaths.
      After adjustment for potential confounders, an age of 65 years or older (adjusted
      odds ratio 3.26, 95% CI 1.08-9.78; p=0.026), and infection by PCR-ribotypes 018
      (6.19, 1.28-29.81; p=0.023) and 056 (13.01; 1.14-148.26; p=0.039) were
      significantly associated with complicated disease outcome. INTERPRETATION: PCR
      ribotypes other than 027 are prevalent in European hospitals. The data emphasise
      the importance of multicountry surveillance to detect and control C difficile
      infection in Europe. FUNDING: European Centre for Disease Prevention and Control.

PMID- 21084116
TI  - Construction of surfactant-like tetra-tail amphiphilic peptide with RGD ligand
      for encapsulation of porphyrin for photodynamic therapy.
AB  - A surfactant-like tetra-tail amphiphilic peptide, [(C(18))(2)K](2)KR(8)GRGDS was
      designed and synthesized for targeted drug delivery. The resulting peptide
      amphiphile, consisting of four hydrophobic aliphatic tails and a hydrophilic
      peptide head group, was able to self-assemble into nanosized micelles in aqueous
      medium at low concentration. Ibuprofen and doxorubicin (DOX) was loaded into
      peptide micelles as model hydrophobic drugs respectively, and the sustained
      release behavior was observed. Due to the incorporation of targeted arginine
      glycine-aspartic acid (RGD) sequences and cell penetrating peptide (CPP) residue
      octaarginine (R(8)), the micelles could be recognized specifically by cancer
      cells, as well as transport through the cell membrane efficiently. The
      observation of laser-scanning confocal microscopy confirmed effective cellular
      uptaking of porphyrin-loaded peptide micelles. Furthermore, the porphyrin-loaded
      micelles exhibited low dark toxicity and high phototoxicity against cancer cells,
      indicating the powerful potential for effective photodynamic therapy. Combined
      with the low cytotoxicity of the peptide against both HeLa and 293T cell lines,
      the surfactant-like peptide developed in this study may be promising in clinical
      application for targeted drug delivery.

PMID- 21084117
TI  - Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte
      multilayer coated implants.
AB  - Drug eluting coatings that can direct the host tissue response to implanted
      medical devices have the potential to ameliorate both the medical and financial
      burden of complications from implantation. However, because many drugs useful in
      this arena are biologic in nature, a paucity of delivery strategies for
      biologics, including growth factors, currently limits the control that can be
      exerted on the implantation environment. Layer-by-Layer (LbL) polyelectrolyte
      multilayer films are highly attractive as ultrathin biologic reservoirs, due to
      the capability to conformally coat difficult geometries, the use of aqueous
      processing likely to preserve fragile protein function, and the tunability of
      incorporation and release profiles. Herein, we describe the first LbL films
      capable of microgram-scale release of the biologic Bone Morphogenetic Protein 2
      (BMP-2), which is capable of directing the host tissue response to create bone
      from native progenitor cells. Ten micrograms of BMP-2 are released over a period
      of two weeks in vitro; less than 1% is released in the first 3 h (compared with
      commercial collagen matrices which can release up to 60% of BMP-2, too quickly to
      induce differentiation). BMP-2 released from LbL films retains its ability to
      induce bone differentiation in MC3T3 E1S4 pre-osteoblasts, as measured by
      induction of alkaline phosphatase and stains for calcium (via Alizarin Red) and
      calcium matrix (via Von Kossa). In vivo, BMP-2 film coated scaffolds were
      compared with film coated scaffolds lacking BMP-2. BMP-2 coatings implanted
      intramuscularly were able to initiate host progenitor cells to differentiate into
      bone, which matured and expanded from four to 9 weeks as measured by MicroCT and
      histology. Such LbL films represent new steps towards controlling and tuning host
      response to implanted medical devices, which may ultimately increase the success
      of implanted devices, provide alternative new approaches toward bone wound
      healing, and lay the foundation for development of a multi-therapeutic release
      coating.

PMID- 21084118
TI  - Efficacy of engineered FVIII-producing skeletal muscle enhanced by growth factor
      releasing co-axial electrospun fibers.
AB  - Co-axial electrospun fibers can offer both topographical and biochemical cues for
      tissue engineering applications. In this study, we demonstrate the sustained
      treatment of hemophilia through a non-viral, tissue engineering approach
      facilitated by growth factor-releasing co-axial electrospun fibers. FVIII
      producing skeletal myotubes were first engineered on aligned electrospun fibers
      in vitro, followed by implantation in hemophilic mice with or without a layer of
      core-shell electrospun fibers designed to provide sustained delivery of
      angiogenic or lymphangiogenic growth factors, which serves to stimulate the
      lymphatic or vascular systems to enhance the FVIII transport from the implant
      site into systemic circulation. Upon subcutaneous implantation into hemophilic
      mice, the construct seamlessly integrated with the host tissue within one month,
      and specifically induced either vascular or lymphatic network infiltration in
      accordance with the growth factors released from the electrospun fibers.
      Engineered constructs that induced angiogenesis resulted in sustained elevation
      of plasma FVIII and significantly reduced blood coagulation time for at least 2
      months. Biomaterials-assisted functional tissue engineering was shown in this
      study to offer protein replacement therapy for a genetic disorder such as
      hemophilia.

PMID- 21084119
TI  - atp2b1a regulates Ca(2+) export during differentiation and regeneration of
      mechanosensory hair cells in zebrafish.
AB  - The molecular mechanisms of development of mechanosensory hair cells have been
      tackled successfully due to in vivo studies in the zebrafish lateral line. The
      enhancer trap (ET) transgenic line, SqET4 was instrumental in these studies even
      despite a lack of a link of its GFP expression pattern to a particular gene(s).
      We mapped the Tol2 transposon insertion of the SqET4 transgenics onto Chr. 4 next
      to a gene encoding Atp2b1a (Pmca1) - one of the four PMCAs acting to export
      Ca(2+) from a cell. atp2b1a expression recapitulates that of GFP during the
      development of mechanoreceptors of the inner ear and lateral line. atp2b1a
      expression correlates with the regeneration of these cells. Thus, SqET4
      represents the Tg:atp2b1a-GFP line, which links Ca(2+) metabolism and the
      differentiation of mechanoreceptors. The morpholino-mediated knockdown of atp2b1a
      blocks Ca(2+) export and affects the division of hair cell progenitors, resulting
      in their accumulation. Under the control of a master gene of hair cells, Atoh1a,
      Atp2b1a functions during progenitor cell proliferation and hair cell
      differentiation. Given the similarity between the phenotypes of atp2b1a morphants
      and embryos treated with the pan-PMCA inhibitor 5(6)-carboxyeosin, Atp2b1a
      emerges as member of the Atp2b family responsible for Ca(2+) export during the
      development of hair cells.

PMID- 21084121
TI  - HLA polymorphisms in Italian children with autism spectrum disorders: results of
      a family based linkage study.
AB  - To verify correlations between HLA and autism spectrum disorders (ASD) we studied
      61 Italian families with an ASD child; results showed such correlation in 65% of
      cases. Case-control and TDT analysis of intrafamilial transmission of SNPs,
      Msats, and HLA markers surrounding the alpha and beta blocks, indicated
      significant positive associations for MOGc*131 and D6S2239*105 alleles in ASD,
      and a negative association of MIB *332 allele in healthy siblings. Polymorphism
      haplotype analysis demonstrated that two haplotypes comprising the TNF-238(G)-TNF
      308(G)-MIB*332-HLA-B*38-HLA-Cw*12 and the D6S265*218-HLA-A*23-MOGc*131
      rs2857766(G) alleles are more frequently transmitted to ASD. MOGc and MIB loci
      are linked with ASD in Italian patients.

PMID- 21084122
TI  - The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus
      vacuolatus can be explained with a toxicokinetic ion-trapping model.
AB  - Several previous studies revealed that pharmaceuticals with aliphatic amine
      function exhibit a higher toxicity toward algae than toward other aquatic
      organisms. Here we investigated the pH-dependent toxicity of the five basic
      pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine,
      and trimipramine. For all of them, the toxicity increased with increasing pH when
      aqueous effect concentrations were considered. Since these pharmaceuticals
      contain a basic amine group that is protonated and thus positively charged at
      physiological pH and because algae are capable of biological homeostasis, i.e.,
      pH inside the algal cell remains virtually independent of variable external pH,
      the speciation of aliphatic amines can be different inside the algal cell
      compared to the external medium. Therefore, we hypothesized that the high
      toxicity of aliphatic amines in algae is a toxicokinetic effect caused by
      speciation and not a toxicodynamic effect caused by a specific mode of toxic
      action. This hypothesis also implies that internal effect concentrations are
      independent on external pH. On this basis we developed a simple toxicokinetic
      model, which assumes that only the neutral molecule is bioavailable and can pass
      the plasma membrane. This assumption is likely to be valid at pH values down to
      two units below the acidity constant (pK(a)). For lower pH values a more complex
      model would have to be evoked that includes, an, albeit smaller, permeability of
      the charged species. For pH>pK(a)-2, we can safely assume that the outer membrane
      serves as insulator and that the charged species is formed inside the cell
      according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion
      trapping model. The input parameters of this model are the measured aqueous
      effect concentrations determined as a function of pH and the membrane-water
      partitioning, which was modelled by the liposome-water partition coefficients of
      the neutral and cationic species. They were deduced from experimentally
      determined liposome-water distribution ratios at various pH values measured with
      an equilibrium dialysis method. The modelled internal effect concentrations were
      independent of the external pH and effective membrane burdens were in the same
      range as for other baseline toxicants found in the literature for algae, daphnids
      and fish. These results confirm that the higher algal toxicity of pharmaceuticals
      with an aliphatic amine group can be explained by a toxicokinetic effect and that
      these pharmaceuticals do not exhibit a specific mode of action in algae but act
      as baseline toxicants.

PMID- 21084120
TI  - Ca(2+) signaling, genes and the cell cycle.
AB  - Changes in the concentration and spatial distribution of Ca(2+) ions in the
      cytoplasm constitute a ubiquitous intracellular signaling module in cellular
      physiology. With the advent of Ca(2+) dyes that allow direct visualization of
      Ca(2+) transients, combined with powerful experimental tools such as
      electrophysiological recordings, intracellular Ca(2+) transients have been
      implicated in practically every aspect of cellular physiology, including cellular
      proliferation. Ca(2+) signals are associated with different phases of the cell
      cycle and interfering with Ca(2+) signaling or downstream pathways often disrupts
      progression of the cell cycle. Although there exists a dependence between Ca(2+)
      signals and the cell cycle the mechanisms involved are not well defined and given
      the cross-talk between Ca(2+) and other signaling modules, it is difficult to
      assess the exact role of Ca(2+) signals in cell cycle progression. Two exceptions
      however, include fertilization and T-cell activation, where well-defined roles
      for Ca(2+) signals in mediating progression through specific stages of the cell
      cycle have been clearly established. In the case of T-cell activation Ca(2+)
      regulates entry into the cell cycle through the induction of gene transcription.

PMID- 21084123
TI  - Preoperative risk factors for postoperative delirium (POD) after urological
      surgery in the elderly.
AB  - The aim of this observational study was to investigate the occurrence of
      postoperative delirium (POD) in elderly patients undergoing urological surgery
      and to identify those factors associated with delirium. Ninety consecutive
      patients (81 males and 9 females; average age of 74.3 +/- 0.40 years), undergoing
      urological surgery in University-Hospital Urological Clinic were selected.
      Personal, medical, cognitive and functional data, biochemical parameters,
      preoperative medications, conduct of surgery and anesthesia and details of
      hemodynamic control were collected as predictors of delirium. After surgery, the
      subjects were divided on the basis of delirium onset within a week observation
      period. Delirium was diagnosed by the Confusion Assessment Method. Delirium
      started the first post-operative day (2F; 6 M) and lasted 3.0 +/- 0.8 days.
      Subjects with POD were significantly older, had a previous history of delirium,
      were more impaired in the instrumental activities of daily living and had poorer
      clock drawing test (CDT) score. Interestingly, a significantly greater number of
      hypotensive events were recorded during anesthesia. Age, cognitive and functional
      status, previous history of delirium and hypotensive episodes intrasurgery are
      the best predictor of POD in this setting. Our findings have implications in
      preventing delirium in elderly by an early and targeted evaluation.

PMID- 21084124
TI  - The development of anemia of inflammation during acute myocardial infarction.
AB  - BACKGROUND: Anemia is associated with an unfavorable outcome in acute myocardial
      infarction (AMI). An acute phase response could contribute to the development of
      anemia in AMI patients. METHODS: We have performed a cross-sectional analysis on
      prospectively collected data at a tertiary hospital catheterization laboratory.
      Multi-adjusted linear regression models were fitted for hemoglobin as the
      dependent variable. ANOVA tests were used to determine interactions between time
      cutoffs of the respective hemoglobin and the concentrations of two inflammatory
      proteins, namely C-reactive protein and fibrinogen. Anemia indices were analyzed
      in a subgroup of 138 male AMI patients for whom frozen serum samples were
      available. RESULTS: Enrolled were 1017 patients (340 with unstable angina
      pectoris [UAP] and 677 with AMI). Correlates of hemoglobin in the AMI group
      included age, male gender, the inflammatory proteins, as well as time from
      symptom onset to angiography (r(2)=0.47; p<0.001). A significant decrease in the
      concentration of hemoglobin with a parallel increase in the inflammatory proteins
      was observed between the time cutoff from symptom onset to angiography only in
      the AMI group for males and females, respectively. A pattern suggestive of anemia
      of inflammation including higher ferritin, lower transferring, lower transferrin
      saturation, and lower serum iron concentrations has been observed in anemic AMI
      patients ( all p<0.05). CONCLUSIONS: Inflammation-sensitive proteins are
      associated with lower hemoglobin concentrations in AMI patients. We therefore
      suggest the possibility that at least part of the hemoglobin drop in AMI prior to
      angiography is related to the anemia of inflammation.

PMID- 21084125
TI  - Development, external validation and clinical usefulness of a practical
      prediction model for radiation-induced dysphagia in lung cancer patients.
AB  - INTRODUCTION: Acute dysphagia is a distressing dose-limiting toxicity occurring
      frequently during concurrent chemo-radiation or high-dose radiotherapy for lung
      cancer. It can lead to treatment interruptions and thus jeopardize survival.
      Although a number of predictive factors have been identified, it is still not
      clear how these could offer assistance for treatment decision making in daily
      clinical practice. Therefore, we have developed and validated a nomogram to
      predict this side-effect. In addition, clinical usefulness was assessed by
      comparing model predictions to physicians' predictions. MATERIALS AND METHODS:
      Clinical data from 469 inoperable lung cancer patients, treated with curative
      intent, were collected prospectively. A prediction model for acute radiation
      induced dysphagia was developed. Model performance was evaluated by the c
      statistic and assessed using bootstrapping as well as two external datasets. In
      addition, a prospective study was conducted comparing model to physicians'
      predictions in 138 patients. RESULTS: The final multivariate model consisted of
      age, gender, WHO performance status, mean esophageal dose (MED), maximum
      esophageal dose (MAXED) and overall treatment time (OTT). The c-statistic,
      assessed by bootstrapping, was 0.77. External validation yielded an AUC of 0.94
      on the Ghent data and 0.77 on the Washington University St. Louis data for
      dysphagia >= grade 3. Comparing model predictions to the physicians' predictions
      resulted in an AUC of 0.75 versus 0.53, respectively. CONCLUSIONS: The proposed
      model performed well was successfully validated and demonstrated the ability to
      predict acute severe dysphagia remarkably better than the physicians. Therefore,
      this model could be used in clinical practice to identify patients at high or low
      risk.

PMID- 21084126
TI  - 16S rRNA pyrosequencing-based investigation of the bacterial community in
      nukadoko, a pickling bed of fermented rice bran.
AB  - Nukadoko is a naturally fermented rice bran mash traditionally used for pickling
      vegetables in Japan; its refreshment and fermentation cycles sometimes continue
      for many years. Here, we investigated the structure and dynamics of the bacterial
      community in nukadoko by conducting pyrosequencing and quantitative polymerase
      chain reaction (PCR) analyses of 16S ribosomal RNA genes (rDNA). Of the 16
      different samples studied, 13 showed Lactobacillus-dominated microbiota,
      suggesting that aged nukadoko samples tend to realize a niche, favorable
      Lactobacillus species. The lactic acid bacterial community of each of the 16
      samples was classified into 3 types according to the presence or absence of 2
      predominant species, Lactobacillus namurensis and Lactobacillus acetotolerans.
      The dynamics of the bacterial community during fermentation and the subsequent
      ripening process were examined using a laboratory model of nukadoko inoculated
      with an aged nukadoko sample (inoculated model). Lb. namurensis grew rapidly in
      the first 2 days, accompanied with a rapid decrease in pH and an increase in
      lactate levels, while Lb. acetotolerans grew with a longer doubling time and slow
      acidification during the 20 days after inoculation. On the other hand,
      spontaneous fermentation of the nukadoko model prepared from fresh rice bran
      without the nukadoko inoculation (inoculant-free model), showed the growth of
      some non-Lactobacillus species such as staphylococci and bacilli within the first
      10 days; thereafter, Lb. namurensis was dominant, while Lb. acetotolerans was not
      detected during the 20-day experimental period. These results suggest that the
      naturally established Lactobacillus community in aged nukadoko is effectively
      involved in the biocontrol of the microbial community of nukadoko during the
      refreshment and fermentation cycles.

PMID- 21084127
TI  - Inhibitory effect of organic acids on arcobacters in culture and their use for
      control of Arcobacter butzleri on chicken skin.
AB  - The inhibitory effects of 17 organic acids (C2-C16 fatty acids, sorbic, benzoic,
      phenylacetic, fumaric, succinic, lactic, malic and citric) on Arcobacter
      butzleri, Arcobacter cryaerophilus and Arcobacter skirrowii were investigated by
      determining their IC50 values, defined as the concentration of acid at which the
      target DNA sequence was expressed at 50% of the positive control level in
      cultures incubated at 30 degrees C for 24 h. DNA was analysed by real-time PCR.
      The Arcobacter strains tested were inhibited by all the organic acids, with the
      sensitivities in the order A. skirrowii > A. cryaerophilus > A. butzleri. Eight
      acids with IC50 values of <1 mg/mL against A. butzleri were tested for their
      effects on A. butzleri inoculated on chicken carcasses at a concentration of 5
      log CFU/g of skin. Inoculated halved carcasses were immersed in solutions of the
      acids at 5 mg/mL for 1 min. Samples of skin were collected from carcass halves
      after storage at 4 degrees C for 0, 1, 2 or 3 days for enumeration of arcobacters
      on Muller-Hinton agar. All eight tested acids suppressed bacterial proliferation.
      The highest inhibitory activities were observed for benzoic, citric, malic and
      sorbic acids. Subsequent sensory analysis revealed benzoic acid to be the most
      suitable organic acid for chicken skin treatment.

PMID- 21084128
TI  - Mixed species biofilms of Listeria monocytogenes and Lactobacillus plantarum show
      enhanced resistance to benzalkonium chloride and peracetic acid.
AB  - We investigated the formation of single and mixed species biofilms of Listeria
      monocytogenes strains EGD-e and LR-991, with Lactobacillus plantarum WCFS1 as
      secondary species, and their resistance to the disinfectants benzalkonium
      chloride and peracetic acid. Modulation of growth, biofilm formation, and biofilm
      composition was achieved by addition of manganese sulfate and/or glucose to the
      BHI medium. Composition analyses of the mixed species biofilms using plate counts
      and fluorescence microscopy with dual fluorophores showed that mixed species
      biofilms were formed in BHI (total count, 8-9 log10 cfu/well) and that they
      contained 1-2 log10 cfu/well more L. monocytogenes than L. plantarum cells.
      Addition of manganese sulfate resulted in equal numbers of both species (total
      count, 8 log10 cfu/well) in the mixed species biofilm, while manganese sulfate in
      combination with glucose, resulted in 1-2 log10 more L. plantarum than L.
      monocytogenes cells (total count, 9 log10 cfu/well). Corresponding single species
      biofilms of L. monocytogenes and L. plantarum contained up to 9 log10 cfu/well.
      Subsequent disinfection treatments showed mixed species biofilms to be more
      resistant to treatments with the selected disinfectants. In BHI with additional
      manganese sulfate, both L. monocytogenes strains and L. plantarum grown in the
      mixed species biofilm showed less than 2 log10 cfu/well inactivation after
      exposure for 15 min to 100 MUg/ml benzalkonium chloride, while single species
      biofilms of both L. monocytogenes strains showed 4.5 log10 cfu/well inactivation
      and single species biofilms of L. plantarum showed 3.3 log10 cfu/well
      inactivation. Our results indicate that L. monocytogenes and L. plantarum mixed
      species biofilms can be more resistant to disinfection treatments than single
      species biofilms.

PMID- 21084129
TI  - Is intraspecific variability of growth and mycotoxin production dependent on
      environmental conditions? A study with Aspergillus carbonarius isolates.
AB  - The aim of this study was to assess the impact of suboptimal environmental
      conditions on the intraspecific variability of A. carbonarius growth and OTA
      production using thirty isolates of A. carbonarius. Three a(w)/temperature
      conditions were tested, one optimal (0.98a(w)/25 degrees C) and two suboptimal:
      0.90a(w)/25 degrees C and 0.98a(w)/37 degrees C as suboptimal water activity and
      temperature, respectively, which might take place through over ripening and
      dehydration of grapes. For each condition, 12 Petri dishes were inoculated, and
      colony growth and OTA production were measured over time. ANOVA revealed
      significant differences among MU and lambda within the 30 assayed isolates.
      Coefficients of variation (CV%) revealed a wider dispersion of growth rates at
      0.90a(w)/25 degrees C compared to 0.98a(w)/25 degrees C, and a more than 4-fold
      higher CV at 0.98a(w)/37 degrees C compared to 0.98a(w)/25 degrees C. However,
      dispersion of lag phases was similar at 0.98a(w)/25 degrees C and 0.90a(w)/25
      degrees C and wider at 0.98a(w)/37 degrees C. There were significant differences
      (p<0.05) among OTA levels (ng/mm(2)) for the different conditions, values being
      lower under marginal conditions, and particularly at 0.98a(w)/37 degrees C.
      Coefficients of variation (CV%) revealed a wider dispersion of OTA production at
      0.90a(w)/25 degrees C compared to 0.98a(w)/25 degrees C, while CV at 0.98a(w)/37
      degrees C was similar to that at 0.98a(w)/25 degrees C. In order to address the
      strain variability in growth initiation and prove the well-established notion of
      reducing OTA in foods by preventing fungal growth, a greater number of strains
      should be included when developing models for conditions that are suboptimal both
      for a(w) for OTA production and temperature levels for growth.

PMID- 21084130
TI  - Regulation of the expression of the hepatocellular sulfate-oxalate exchanger SAT
      1 (SLC26A1) by glyoxylate: a metabolic link between liver and kidney?

PMID- 21084132
TI  - Long distance calling for liver regeneration: identification of neuroendocrine
      signalling pathways activated after partial hepatectomy.

PMID- 21084134
TI  - Locomotor impairment and cerebrocortical oxidative stress in portal vein ligated
      rats in vivo.
AB  - BACKGROUND & AIMS: Oxidative/nitrosative stress plays an important role in the
      pathogenesis of hepatic encephalopathy and ammonia toxicity. The present study
      was undertaken in order to investigate the impact of portal vein ligation on
      cerebrocortical oxidative stress and its relation to locomotor activity. METHODS:
      Cerebral protein tyrosine nitration, RNA oxidation, locomotor activity, and
      microglia activation were studied in rats that underwent portal vein ligation
      (PVL). RESULTS: Two weeks after PVL, increased levels of protein tyrosine
      nitration and RNA oxidation were found in the brain. PVL rats exhibited
      hyperammonemia and reduced locomotor behaviour, but displayed no signs of
      microglia activation or upregulation of the mRNAs for interleukin-1beta and tumor
      necrosis factor-alpha. PVL also had no effect on astrocytic glutamate transporter
      or inducible nitric-oxide synthase expression. Only cerebral Il-6 mRNA levels
      were increased. Daily administration of indomethacin prevented PVL-induced
      protein tyrosine nitration, RNA oxidation, Il-6 mRNA increase, and the impairment
      of locomotor activity, but did not prevent PVL-induced hyperammonemia.
      CONCLUSIONS: The data suggest that PVL triggers oxidative/nitrosative stress in
      the brain without activation of microglia and neuroinflammation. Prevention of
      protein tyrosine nitration and RNA oxidation by indomethacin also prevents the
      disturbances in locomotor activity pointing to a relevance of oxidative stress in
      the pathophysiology of HE.

PMID- 21084135
TI  - Synthesis and biological evaluation of novel 2,4-disubstituted-1,3-thiazoles as
      anti-Candida spp. agents.
AB  - A new series of [4-(4'-substituted-phenyl)thiazol-2-yl]hydrazine derivatives were
      synthesized in good yield (86-99%) and characterized by elemental analysis, IR,
      (1)H NMR, and mass spectral studies. The compounds were assayed for their in
      vitro broad-spectrum antifungal activity, compared to clotrimazole and
      fluconazole, against 20 clinical isolates of pathogenic Candida spp.,
      representing five different species. The results showed that the presence of
      heterocyclic or bicyclic rings on hydrazone moiety in position C2 of thiazole
      revealed a promising selective inhibitory activity especially against Candida
      albicans and Candida glabrata.

PMID- 21084131
TI  - Liver antigen-presenting cells.
AB  - The liver is an organ in which several major pathogens evade immune clearance and
      achieve chronicity. How do they do it? Recent research has documented multiple
      mechanisms by which immune responses in the liver are biased towards tolerance.
      In this review, the induction of local, intrahepatic tolerance is explored from
      the perspective of antigen presentation. Experiments support the role not only of
      liver dendritic cell subsets but also of diverse subsets of unconventional
      antigen-presenting cells in inducing immune suppression. The literature on this
      topic is controversial and sometimes contradictory, making it difficult to
      formulate a unified model of antigen handling and T cell priming in the liver.
      Here I offer a critical review of the state of the art in understanding antigen
      presentation in the liver.

PMID- 21084136
TI  - Collaborative testing: assessing teamwork and critical thinking behaviors in
      baccalaureate nursing students.
AB  - The purpose of this study was to foster teamwork and critical thinking behaviors
      in baccalaureate nursing students using a collaborative testing environment.
      Collaborative testing affords the nurse educator a unique opportunity to actively
      influence the development of critical thinking skills directly influencing the
      nursing student's ability to solve complex patient problems. Using a quasi
      experimental approach exam scores from students in prior semesters were compared
      to students in several semesters using collaborative testing in one undergraduate
      course taught by the same faculty. In the experimental group collaborative
      testing was used in the two unit examinations, while the final examination
      remained individual. For collaborative testing the students were grouped by
      random assignment. They were not allowed the use of notes, textbooks, or other
      resource materials. Any student who wished to work alone was allowed do so and
      any student coming late (within 15 min of examination beginning) was required to
      work alone. Each student submitted individual examination answer forms, and
      groups were not required to reach consensus. Collaborative testing is one means
      to foster critical thinking by allowing students to solve complex patient
      problems within an examination environment. This better prepares them for
      national certification exams.

PMID- 21084137
TI  - Computer-assisted condylar reconstruction in bilateral ankylosis of the
      temporomandibular joint using autogenous coronoid process.
AB  - During the past 10 years, more than 20 patients a year have been treated at our
      centre for bilateral ankylosis of the temporomandibular joint (TMJ). Here we
      describe the use of computer-assisted three-dimensional surgical planning and its
      clinical effects in condylar reconstruction for such patients using autogenous
      coronoid process. Sixteen patients with bilateral bony ankylosis of the TMJ from
      March 2006 to March 2009 were randomly divided into 2 groups and treated by
      bilateral osteoarthrectomy and condylar reconstruction by free grafting of
      autogenous coronoid process with and without three-dimensional simulation using
      Surgicase CMFTM (Materialise, Belgium) software. Clinical examination,
      radiographs, photographs, and details of the operation and its outcome were used
      postoperatively to evaluate the clinical effects of the technique. Satisfactory
      mouth opening was achieved in all cases. There were fewer postoperative
      malocclusions among patients who had three-dimensional simulation. The
      combination of computer-assisted three-dimensional surgical planning and
      simulation and free grafting of autogenous coronoid process is a sound and
      predictable method for the reconstruction of condyles in patients with bilateral
      ankylosis of the TMJ as it makes the operation easier and more accurate.

PMID- 21084138
TI  - Biomechanical evaluation of fixation strength of conventional and expansive
      pedicle screws with or without calcium based cement augmentation.
AB  - BACKGROUND: The expansive pedicle screw was originally developed to be installed
      in the bone of compromised quality, but there are some concerns whether it can
      provide enough fixation strength in the spine with osteoporosis or severe
      osteoporosis. METHODS: Twelve fresh human cadaver spines were stratified into
      four levels: normal, osteopenia, osteoporosis and severe osteoporosis. The
      vertebra was bilaterally instrumented with pedicle screws according to four
      protocols, including conventional pedicle screw without augmentation, expansive
      pedicle screw without augmentation, conventional screw with augmentation and
      expansive screw with augmentation. Screw pullout tests were conducted. FINDINGS:
      Given the same specimen, the fixation strength of expansive screw was
      significantly higher than that of the conventional screw. When the same type of
      screw was used, the fixation strength of the calcium based cement augmented group
      was stronger than that of the non-augmented group. The pullout strength and
      stiffness of the expansive screw, augmented conventional screw and augmented
      expansive screw groups at the osteoporotic level were comparable to those of the
      conventional pedicle screw group at the osteopenic level. However, under the
      severely osteoporotic bone environment, the pullout strength of pedicle screw
      with whatever placement protocol was significantly lower than that of the
      conventional screw group at the osteopenic level. INTERPRETATION: Our results
      demonstrate that (i) the expansive pedicle screw appears feasible and safe in
      either osteopenic or osteoporotic spine; (ii) calcium based cement augmentation
      can offer improved initial fixation strength of pedicle screws.; and (iii) no
      screw placement protocol we examined is efficacious in the bone at the severely
      osteoporotic level.

PMID- 21084139
TI  - The study of urban metabolism and its applications to urban planning and design.
AB  - Following formative work in the 1970s, disappearance in the 1980s, and
      reemergence in the 1990s, a chronological review shows that the past decade has
      witnessed increasing interest in the study of urban metabolism. The review finds
      that there are two related, non-conflicting, schools of urban metabolism: one
      following Odum describes metabolism in terms of energy equivalents; while the
      second more broadly expresses a city's flows of water, materials and nutrients in
      terms of mass fluxes. Four example applications of urban metabolism studies are
      discussed: urban sustainability indicators; inputs to urban greenhouse gas
      emissions calculation; mathematical models of urban metabolism for policy
      analysis; and as a basis for sustainable urban design. Future directions include
      fuller integration of social, health and economic indicators into the urban
      metabolism framework, while tackling the great sustainability challenge of
      reconstructing cities.

PMID- 21084140
TI  - Atmospheric particle characterization, distribution, and deposition in Xi'an,
      Shaanxi Province, Central China.
AB  - Physical characterization and chemical analysis of settled dusts collected in
      Xi'an from November 2007 to December 2008 show that (1) dust deposition rates
      ranged from 14.6 to 350.4 g m(-2) yr(-1). The average deposition rate (76.7 g m(
      2) yr(-1)) ranks the 11th out of 56 dust deposition rates observed throughout the
      world. The coal-burning power was the major particle source; (2) on average
      (except site 4), ~10% of the settled dusts having size <2.6, ~30% having size
      <10.5, and >70% having size <30 MUm; (3) the concentrations for 20 out of 27
      elements analyzed were upto 18 times higher than their soil background values in
      China. With such high deposition rates of dusts that contain elevated levels of
      toxic elements, actions should be taken to reduce emission and studies are needed
      to assess the potential impacts of settled particles on surface ecosystem, water
      resource, and human health in the area.

PMID- 21084141
TI  - Historical trends of polychlorinated dibenzo-p-dioxins and dibenzofurans in three
      dated sediment cores from Mexico.
AB  - This paper describes the first report of dioxins and furans (PCDDs/Fs) in
      sediment cores from Mexico. Sedimentation rates and vertical fluxes were
      estimated using (210)Pb dating. Two cores correspond to marine sediments and one
      to an endorheic lake. Concentrations of PCDDs/Fs found in the three sites are
      typical of non-impacted areas with low concentrations when compared to reference
      values. However the PCDDs/Fs sediment profiles show an increasing concentration
      trend in the upper core sections. This behavior is different from that found at
      many sites around the globe where diminishing concentrations have been reported.
      A strong predominance of OCDD was observed, and a comparison to typical
      composition profiles of industrial and other sources did not result in clear
      origin assignments for these measured compounds. We suggest that local sources
      may be responsible for the increase in concentration and, because these
      undetermined sources have not been curtailed, their importance is still growing.

PMID- 21084142
TI  - Predictors of alcohol use prior to pregnancy recognition among township women in
      Cape Town, South Africa.
AB  - South Africa has the highest prevalence of Fetal Alcohol Spectrum Disorders
      (FASDs) in the world. The purpose of this study was to identify high risk factors
      associated with drinking alcohol prior to pregnancy recognition in 24
      neighborhoods in the Cape Flats outside Cape Town, South Africa. An interviewer
      assessed risk among 619 pregnant Black/African women between the ages of 18 and
      41 years. Logistic regression analyses explored factors associated with drinking
      alcohol post conception but prior to pregnancy recognition. Forced multiple
      logistic regression analysis revealed that drinking prior to pregnancy
      recognition was associated with being younger, single, having better living
      conditions, smoking, having a longer gestation prior to pregnancy recognition,
      having a greater number of sexual partners, and a higher incidence of intimate
      partner violence. Depressive symptoms tended to be higher among alcohol users.
      These risk factors were consistent with other research on the characteristics of
      South African women having children with a diagnosis of Fetal Alcohol Spectrum
      Disorders and/or of non pregnant women at high risk for an alcohol-exposed
      pregnancy. These findings highlight the need for women of child-bearing age to be
      routinely screened for alcohol use and its associated risk factors. Intervention
      efforts could be integrated into health initiatives already present in South
      Africa including the prevention and treatment of HIV/AIDS, tuberculosis, and
      malnutrition. Preconception care is particularly important since pregnancy
      recognition often occurs several weeks to months following conception and could
      be implemented by South African community health workers. These endeavors should
      facilitate national goals of healthier pregnancies and the elimination of FASDs
      in South Africa.

PMID- 21084144
TI  - [Surgical issues and outcomes in ischial pressure sores treatment].
AB  - INTRODUCTION: Ischiatic pressure sores are frequent in spinal cord injury
      patients, associated with bad prognosis and high recurrence rate. Many surgical
      techniques were described, including surgical debridement followed by pedicled
      flap coverage. We aim to propose a practical decision tree for primary or
      secondary ischial pressure sore treatment. PATIENTS AND METHOD: Our series of 48
      operated ischial sores with an average follow up of 4 years (range 2 to 8years)
      is analyzed and compared to previously published reports. Surgical techniques are
      discussed according to their specific indications. RESULTS: The optimal
      recurrence rate in published reports about pressure sore treatment is 20%; a rate
      inferior to 19% is found in our series, showing the equal importance of flap
      selection and postoperative care and education. Depending on each situation,
      various available flaps are described and compared: gluteus maximus flap, biceps
      femoris flap, gracilis flap, tensor fascia lata flap, fasciocutaneous thigh
      flaps, rectus femoris and vastus lateralis flap, rectus abdominis flap. Specific
      surgical indications for more extensive wounds are studied: resection
      arthroplasty of the hip, hip disarticulation, fillet flaps from the leg,
      microsurgery. CONCLUSION: Based upon our experience, a decision tree summarizes
      our proposition of flap selection, depending on the wound size and the patient
      background.

PMID- 21084143
TI  - [Advantages of the superior areolar approach for tuberous breast II and III
      correction with implants].
AB  - Tuberous breast is a mammary malformation that remains difficult to treat in most
      cases. It results from an abnormal development of the mammary base, mainly at the
      lower pole of the breast. The superficialis fascia is adherent to the dermis and
      deep plane. For type II and III of Grolleau's classification, we were confronted
      by some difficulties with inferior areolar approach as in Puckett's or Ribeiro's
      techniques. We had frequently an insufficient glandular volume at the inferior
      part of the breast and an early look of a "double bubble" deformity. We propose a
      technical modification to these procedures using a superior hemiareolar approach
      to place the implant. Associated with an incision of the deep part of the
      superficialis fascia, it provides a good-shaped lower pole of the breast by
      preserving glandular volume at this part and reduces the apparition of "double
      bubble". We operated on 14 types II-III tuberous breasts on nine female patients
      and had no significant complication. The mean follow-up is 36 months and the
      results were very satisfying for the patient and her surgeon.

PMID- 21084145
TI  - [Evaluation of an information network and nurse consultation for breast
      reconstruction].
AB  - To evaluate the installation of a nurse consultation and an interactive support
      DVD in breast reconstruction. To judge utility of these new tools of information
      for the patients. MATERIAL AND METHOD: The nurse consultation is carried out
      after the initial consultation of the surgeon; during this consultation, a DVD
      containing of the interviews is given taking again the information given as well
      as patients' evidence on their path of care. Evaluation of the information given
      by the surgeon and the nurse (eight items from surgical techniques to
      convalescence). Evaluation of the interest and comprehensibility. Quotation from
      0 to 10. RESULTS: Evaluation by anonymous questionnaire on 110 women, between
      February and December 2007. Rate of participation: 72.7% (80/110); mean age:
      51.5+/-9.2. Information given is considered to be useful (surgeon: quotation
      above 9.3/10 in function of the items, nurse: quotation above 9.4) and
      comprehensible (quotation above 8.7/quotation above 8.9). The information made by
      the nurse is more comprehensible than that done by the surgeon, for over all
      items. The nurse consultation is considered to be very useful (9.45). Seventy
      percent of the patients learned from extra informations, compared to the
      consultation of the surgeon. This consultation does not have a direct influence
      on the choice of the technique (5.45/10), the consultation of the surgeon
      remaining predominant. Fifty percent of the women still learned from new
      informations, by using the DVD. On the other hand, it has little influence on the
      choice of the technique (4.84/10). The nurse consultation and the DVD are well
      conceived because 80% of the women did not need more information. The predominant
      elements in the choice of the patients are the surgeon consultation, then the
      nurse consultation and then the DVD. The total index of satisfaction is very good
      9.31/10 (surgeon: 9.24, nurse 9.56, DVD 9.11). CONCLUSION: The nurse consultation
      and the DVD are not replacement components of the surgeon consultation. They are
      complementary and have an important role in the acquisition of information and
      the psychological support of the patients. The surgeon initial consultation
      remains predominent in the decision of choice by the patients, it must remain the
      most complete possible.

PMID- 21084146
TI  - The limitations of environmental management systems in Australian agriculture.
AB  - The efficacy of government-supported programs to encourage improved management of
      land and water systems associated with agricultural land in Australia has been
      mixed. The broad approach of Australian governments is reviewed briefly. Evidence
      is presented from case assessments of a program to promote adoption of
      environmental management systems (EMSs) to improve environmental outcomes from
      agricultural practices. EMSs are systems implemented to manage the environmental
      impacts and ameliorate environmental risk associated with business activity. Data
      are presented on reported EMS activity and experience of four selected groups of
      farmers in Victoria, south-eastern Australia, representing broad-acre cropping,
      beef and dairy farming. The pro-environmental behaviours of farmers were mediated
      through voluntary adoption of government and industry sponsored EMSs, often with
      financial incentives and other support. Findings from the study were that
      adoption of EMS practices with sufficient public benefits is unlikely to occur at
      sufficient scale for significant environmental impact. Farmers more readily
      adopted practices which were financially beneficial than those which had a
      positive environmental impact. Although the focus on voluntary market-based
      instrument (MBI) type programs is popular in western countries, enforcing
      regulation is an important, but usually politically unpopular, component of land
      use policy. The comparative advantage of EMSs differed for the industries
      studied, but overall there were insufficient market drivers for widespread EMS
      adoption in Australia. Environmental outcomes could be more effectively achieved
      by directly funding land management practices which have highest public net
      benefits. Having a clear and unambiguous management objective for a particular
      land management policy is more likely to achieve outcomes than having multiple
      objectives as occurs in a number of international programs currently.

PMID- 21084147
TI  - Implementation of the EU environmental noise directive: lessons from the first
      phase of strategic noise mapping and action planning in Ireland.
AB  - The first phase of noise mapping and action planning in Ireland, in accordance
      with EU Directive 2002/49/EC, is now complete. In total this included one
      agglomeration, one airport and approximately 600 km of major roads outside the
      agglomeration. These noise maps describe the level of noise exposure of
      approximately 1.25 million people. The first phase of noise mapping was dealt
      with by five noise mapping bodies while 26 action planning authorities were
      involved in the development of the associated action plans. The second phase of
      noise mapping, due to be completed in 2012, sees a reduction in the defined
      thresholds describing the required agglomerations, roads and railways that have
      to be mapped. This will have a significant impact on the extent of mapping
      required. In Ireland this will result in an increased number of local authorities
      being required to develop strategic noise maps for their area along with the
      further development of associated action plans. It is appropriate at this point
      to review the work process and results from the first phase of noise mapping in
      Ireland in order to establish areas that could be improved, throughout the noise
      mapping project. In this paper a review of the implementation procedures
      focussing on (dominant) road traffic noise is presented. It is identified that
      more standardisation is needed and this could be achieved by the establishment of
      a national expert steering group.

PMID- 21084148
TI  - Long-term leaching of uranium from different waste matrices.
AB  - A semi-dynamic leaching test was carried out for metallurgical wastes and ore
      samples from the uranium and copper mining industry over a 142 day period using
      distilled water and 0.1N NaNO(3) as solvents. Laser fluorimetry was used as the
      analytical technique to determine the total uranium content in the leachates. The
      cumulative leach fraction (CLF) of uranium release from the samples was
      calculated to be 0.22, 0.22, 0.07 and 0.39% for rock, uranium tailings, copper
      kinker ash samples and copper tailings respectively using distilled water as
      solvent and 0.31, 0.27, 0.05 and 0.59% for the same matrices using 0.1N NaNO(3).
      The release of mobile uranium fraction was very slow, being faster in the initial
      stage and then attained a near steady state condition. The diffusion coefficient
      and bulk release of uranium from the samples have been calculated. The processes
      governing the release of uranium from these matrices have been identified to be
      surface wash-off and diffusion. Hence the use of weak solvents (leach out the
      mobile/exchangeable fraction of uranium) under semi-dynamic conditions aids the
      determination of leaching parameters and identification of the leaching mechanism
      for mobile uranium fraction from different matrices by slow leaching processes.

PMID- 21084149
TI  - Review of socio-economic drivers of community acceptance and adoption of
      decentralised water systems.
AB  - The aim of this paper is to highlight key social and economic drivers crucial to
      understanding community acceptance and adoption of decentralised water systems.
      The review focused on social science literature pertaining to alternative forms
      of household water, with an emphasis on research examining decentralised water
      acceptance. Researchers consistently reported that most communities were open to
      alternative water sources for domestic applications; however, this was highly
      dependent upon the level of personal contact with the water. Acceptance and
      adoption of alternative water technology, such as decentralised systems, was
      influenced by risk perception, water culture, and threat perception. Motivational
      drivers were also identified as potentially influencing adoption of decentralised
      systems. A clear limitation of the literature was found to be an over-reliance on
      measuring people's intentions to adopt alternative water systems and building a
      conceptual understanding of acceptance solely on hypothetical water supply
      scenarios. Further, within the social science literature there appears to be a
      skewing towards focusing on acceptance of centralised alternative water, such as
      recycled and desalinated water systems. Although there are some research outcomes
      that are generalizable to the decentralised water context, it is clear that there
      is a significant gap in the knowledge base of social drivers specific to the
      acceptance of decentralised water systems and the factors contributing to its
      widespread use. It is recommended that future research focus on examining public
      attitudes relevant to decentralised water systems, as well as adoption behaviours
      among current users of these systems. This will assist in developing policies
      specific to domestic decentralised water use.

PMID- 21084150
TI  - Examining the technology acceptance for dismantling of waste printed circuit
      boards in light of recycling and environmental concerns.
AB  - The dismantling of printed circuit board assemblies (PCBAs) and the recovery of
      their useful materials can lead to serious environmental impacts mainly due to
      their complicated physical structure and the variety of toxic elements contained
      in their material composition. So far, less attention has been paid to their
      responsible recycling compared to that of bare printed circuit boards. Combined
      with other materials recovery process, proper dismantling of PCBAs is beneficial
      to conserve scarce resources, reuse the components, and eliminate or safely
      dispose of hazardous materials. In analyzing the generation, resources potential
      and hazardous risk of scrap PCBAs, technologies used for the dismantling of waste
      PCBAs have been widely investigated and reviewed from the aspects of both
      industrial application and laboratory-scale studies. In addition, the feasibility
      of PCBA dismantling has been discussed, the determinants of which, including the
      heating conditions and mechanical properties have been identified. Moreover, this
      paper evaluates the environmental consequences caused by the dismantling of
      PCBAs.

PMID- 21084151
TI  - Prominent papillary muscles in Fabry disease: a diagnostic marker?
AB  - Fabry disease is often linked with a prominent papillary muscle. It remains
      unknown whether this sign could be used as a diagnostic marker to screen for
      Fabry patients. Standard echo was performed in 101 consecutive patients with
      concentric left ventricular (LV) hypertrophy (28 Fabry, 30 Friedreich, 34
      isolated arterial hypertension, 9 amyloidosis) and 50 healthy controls. In
      addition, the areas of both papillary muscles, as well as the LV endocardial
      circumference, were manually traced in short axis views. A ratio of papillary
      muscle size to LV circumference was calculated (PM_LV_ratio). The papillary
      muscle area was positively correlated to LV wall thickness in this cohort (p <
      0.0001; r = 0.58). In all patient subgroups, the absolute papillary muscle area
      was significantly enlarged and the PM_LV_ratio was significantly higher when
      compared with controls. However, Fabry patients showed a significantly larger
      absolute papillary muscle area than Friedreich and amyloidosis patients and a
      higher PM_LV_ratio than hypertensive and amyloidosis patients. Enlarged absolute
      papillary muscle area was evidenced in 21 (75%), and increased PM_LV_ratio was
      found in 22 (78%) of 28 Fabry patients. Combining these two parameters yields a
      sensitivity of 75% and specificity of 86% for diagnosing Fabry disease with LV
      hypertrophy. Only 10 of 73 non-Fabry patients (14%) (4 Friedreich, 1 amyloidosis,
      5 hypertensive) showed an increased absolute papillary muscle area and
      PM_LV_ratio. In conclusion, this study confirmed the assumption that the
      prominent papillary muscle could be an echocardiographic marker for detection of
      Fabry patients with concentric LV hypertrophy.

PMID- 21084152
TI  - Analysis of index modulation in microembolic Doppler signals part I: radiation
      force as a new hypothesis-simulations.
AB  - The purpose of this study was to reveal the cause of frequency modulation (FM)
      present in microembolic Doppler ultrasound signals. This novel explanation should
      help the development of sensitive microembolus discrimination techniques. We
      suggest that the frequency modulation detected is caused by the ultrasonic
      radiation force (URF) acting directly on microemboli. The frequency modulation
      and the imposed displacement were calculated using a numerical dynamic model. By
      setting simulation parameters with practical values, it was possible to reproduce
      most microembolic frequency modulation signatures. The most interesting findings
      in this study were that: (1) the ultrasound radiation force acting on a gaseous
      microembolus and its corresponding cumulative displacement were far higher than
      those obtained for a solid microembolus, and that is encouraging for
      discrimination purposes; and 2) the calculated frequency modulation indices
      (FMIs) (~20 kHz) were in good agreement with literature results. By taking into
      account the URF, the flow pulsatility, the beam-to-flow angle and both the
      velocity and the ultrasound beam profiles, it was possible to explain all erratic
      FM signatures of a microbubble. Finally, by measuring FMI from simulated Doppler
      signals and by using a constant threshold of 1 KHz, it was possible to
      discriminate gaseous from solid microemboli with ease.

PMID- 21084153
TI  - Effect of shock wave treatment on platelet-rich plasma added to osteoblast
      cultures.
AB  - The aim of this study was to verify the effects on osteoblast cultures of adding
      a platelet-rich plasma (PRP) concentrate pretreated with 500 shock wave (SW) at
      an energy flow density of 0.17 mJ/mm(2), emitted by an electromagnetic generator
      Minilith SL1 (STORZ, Germany), reproducing the conditions of our previous study
      in which we apply SW directly on osteoblasts. Real-time PCR showed that in
      osteoblast cultures with added PRP pretreated with SW, there was an increased
      expression at 48 h of insulin-like growth factor binding protein 3 (IGFBP-3) and
      runt-related transcription factor 2 (RUNX2) and at 72 h, of collagen type I,
      osteocalcin, insulin-like growth factor 1 (IGF-1) as well as IGFBP-3. Western
      blotting confirmed the increased protein synthesis of IGFBP-3. This experience
      suggests that extracorporeal shock wave treatment (ESWT) should stimulate
      osteogenesis also by indirect platelets-mediated network. It therefore seems
      possible that combining the two methods, ESWT and bioengineering procedures to
      infiltrate PRP and growth factors, could be a successful approach.

PMID- 21084154
TI  - Changes in fetal and maternal Doppler parameters observed during acute severe
      hypertension treatment with hydralazine or labetalol: a randomized controlled
      trial.
AB  - We evaluated 16 pregnant women with gestational age between 20 and 32 weeks in
      acute severe hypertension which were randomly allocated to receive either
      hydralazine or labetalol. Blood pressure and Doppler ultrasound parameters from
      maternal uterine and fetal middle cerebral and umbilical arteries were assessed
      during acute severe hypertension and after treatment. A significant reduction in
      systolic and diastolic blood pressure was observed in both groups. A significant
      change in Doppler parameters was observed only in pregnant women who received
      hydralazine: an increase in uterine arteries resistance index. We concluded that
      both drugs were highly effective in reducing blood pressure in these women.
      Despite the observed increase in resistance index of uterine arteries associated
      with hydralazine, the use of hydralazine and labetalol were not related to any
      significant changes in fetal Doppler, which is reassuring about the safety of
      these drugs when treating acute severe hypertension in pregnancy.

PMID- 21084155
TI  - Intraoperative ultrasound score to predict recurrent hepatocellular carcinoma
      after radical treatments.
AB  - Despite the high complete necrosis rate of radio-frequency ablation (RFA) or the
      complete removal following curative hepatic resection (HR), recurrent
      hepatocellular carcinoma (HCC) remains a significant problem. The aim of the
      study is to identify some intraoperative ultrasound (IOUS) patterns, predicting
      intrahepatic recurrences. From January 1997 to July 2009, 410 patients with HCC
      were treated (162 HR and 248 RFA through a surgical access). All patients were
      submitted to IOUS examination: 148 IOUS were performed during the laparotomic
      access while 262 IOUS were performed during the laparoscopic access. Primary HCC
      was classified according to diameter, HCC pattern (nodular or infiltrative),
      echogenicity (hyper- or hypo-echoic), echotexture (homogeneous or inhomogeneous),
      capsular invasion, mosaic pattern, nodule in nodule aspect and infiltration of
      portal vessels. Number of HCC nodules was also considered. Multivariate analysis
      (Cox model) was performed to determine features associated with recurrent HCC
      using IOUS patterns that independently predicted recurrent HCC, a IOUS score was
      developed. The patients were followed for 3-127 months, (median follow-up: 21.5
      months). In 220 patients (54%), intrahepatic recurrences occurred. In 155
      patients (38%), distant intrahepatic recurrences arose in different segments at
      the primary tumor site. In 65 HCC cases (16%), local recurrences were found. At
      multivariate analysis, multiple nodules, HCC diameter (>20 mm), HCC pattern
      (infiltrative), hyperechoic nodule and portal infiltration were statistically
      significant for risk factor of intrahepatic recurrences. Therefore, a IOUS
      scoring system was calculated on the basis of multivariate analysis and
      identified three risk categories of patients: in group 1 recurrences occurred in
      37%, group 2 in 46% and group 3 in 66% (p = 0.0001). IOUS is an accurate staging
      tool during "surgical" procedures. This study showed an added value of IOUS: it
      permitted to identify ultrasound patterns, which can predict the risk of HCC
      recurrences. The calculated IOUS score permits to intraoperatively evaluate the
      actual surgical choice and to program the best treatment strategies during the
      follow-up period.

PMID- 21084156
TI  - Characterization of center frequency and bandwidth of broadband ultrasound
      reflected by the articular cartilage to subchondral bone interface.
AB  - Osteoarthritis (OA) produces degenerative changes both in articular cartilage and
      subchondral bone. During OA, reflection of high frequency ultrasound from the
      cartilage-bone interface is affected by both changes in attenuation of the
      cartilage layer and acoustic properties of the interface. The objective of this
      study was to experimentally investigate the spectral content of ultrasound
      reflection from the cartilage-bone interface. Specifically, we analyzed the
      center frequency and -6 dB bandwidth of the broadband high-frequency (40 MHz)
      ultrasound signal. Intact bovine articular cartilage samples with and without the
      underlying subchondral bone (n = 6) were measured in vitro using a commercial
      high-frequency ultrasound scanner. Furthermore, the diagnostic potential of the
      measurement of center frequency and bandwidth for OA was studied with another
      series of bovine articular cartilage samples (n = 40) after enzymatic
      degradations of tissue proteoglycans and collagen. Compared with the reference
      spectrum at the same depth from a perfect reflector, a major downshift (>51%) of
      the center frequency and a reduction (>42%) of the bandwidth were observed in
      both sample groups when analyzing the ultrasound reflection from the cartilage
      bone interface. The results suggest that attenuation in the cartilage layer
      primarily controls the observed downshift of the center frequency and acoustic
      properties of the subchondral bone play only a minor role in affecting the
      spectrum of the cartilage-bone interface. Changes in the ultrasound bandwidth of
      the cartilage-bone interface signals, compared with reference signals, were found
      to vary more than those in the center frequency in both cartilage sample groups.
      Compared with pretreatment values, a significant downshift in center frequency (p
      < 0.01) and a minor reduction in bandwidth of spectra from the cartilage-bone
      interface were recorded after chemical degradation of proteoglycans with trypsin.
      In contrast, center frequency and bandwidth of the echoes from the cartilage-bone
      interface did not change after the chemical degradation of cartilage collagen
      fibrils. The results suggest that proteoglycan loss, typical to OA, may be
      detected via the changes in the center frequency of the ultrasound reflected from
      the cartilage-bone interface.

PMID- 21084157
TI  - Ultrasound reverses multidrug resistance in human cancer cells by altering gene
      expression of ABC transporter proteins and Bax protein.
AB  - Multidrug resistance (MDR) is the major obstacle to successful chemotherapy of
      human malignancies and strategies for overcoming MDR phenomena are still
      unavailable to clinical use. Previous results showed that ultrasound (US)
      exposure could make MDR cancer cells become more sensitive to anticancer drugs,
      and the physical parameters of US exposure could adjust the uptake and retention
      of rhodamine 123 in MDR cells. In this study, we investigated the mechanisms of
      therapeutic ultrasound as a physical approach to overcoming MDR in a multidrug
      resistant human hepatocarcinoma cell line (HepG2/ADM). Our results demonstrated
      that the percentage of P-glycoprotein(+) (P-gp), multidrug resistance-associated
      protein(+) (MRP) and lung resistance-related protein(+) (LRP) cells was 96.97% +/
      2.41%, 20.84% +/- 3.12% and 1.16% +/- 0.59% in HepG2/ADM cells, and 62.84% +/-
      3.42%, 10.26% +/- 1.18% and 3.05% +/- 0.37% in US-exposed HepG2/ADM cells,
      respectively. A significant decrease in the number of P-gp(+) and MRP(+) cells
      was observed between US-exposed HepG2/ADM and HepG2/ADM cells (p < 0.05). Using
      RT-PCR technique, we found that US could significantly downregulate the
      expression of P-glycoprotein (P-gp) and (MRP) at the mRNA level in HepG2/ADM
      cells. Compared with the control, the percentage of apoptotic cell death was
      significantly increased in HepG2/ADM after ultrasound exposure. Using
      immunocytochemistry, the percentage of Bcl-2(+) and Bax(+) cells was 21.7% and
      4.1% in the control, and 18.46% and 8.1% in the US-exposed cells, respectively.
      The percentage of Bax(+) cells was significantly higher in US-exposed HepG2/ADM
      cells (p < 0.05), suggesting that US exposure could lead to cellular apoptosis in
      HepG2/ADM cells. It is concluded that US exposure could reverse MDR in HepG2/ADM
      cells via decreasing P-gp and MRP levels and their mRNA expressions and
      increasing expression of Bax protein. It may lead to the development of a novel
      strategy of using a targeted, noninvasive physical approach for the induction of
      MDR reversal in cancer cells.

PMID- 21084158
TI  - Novel tissue mimicking materials for high frequency breast ultrasound phantoms.
AB  - The development and acoustical characterisation of a range of novel agar-based
      tissue mimicking material (TMMs) for use in clinically relevant, quality
      assurance (QA) and anthropomorphic breast phantoms are presented. The novel agar
      based TMMs described in this study are based on a comprehensive, systematic
      variation of the ingredients in the International Electrotechnical Commission
      (IEC) TMM. A novel, solid fat-mimicking material was also developed and
      acoustically characterised. Acoustical characterisation was carried out using an
      in-house scanning acoustic macroscope at low (7.5 MHz) and high frequencies (20
      MHz), using the pulse-echo insertion technique. The speeds of sound range from
      1490 to 1570 m. s(-1), attenuation coefficients range from 0.1 to 0.9 dB. cm(-1).
      MHz(-1) and relative backscatter ranges from 0 to -20 dB. It was determined that
      tissues can be mimicked in terms of independently controllable speeds of sound
      and attenuation coefficients. These properties make these novel TMMs suitable for
      use in clinically relevant QA and anthropomorphic phantoms and would potentially
      be useful for other high frequency applications such as intravascular and small
      animal imaging.

PMID- 21084159
TI  - Effect of magnetite nanoparticle agglomerates on the destruction of tumor
      spheroids using high intensity focused ultrasound.
AB  - Magnetite (Fe(3)O(4)) nanoparticle agglomerates have been shown to enhance the
      degree of inertial cavitation induced by high-intensity focused ultrasound
      (HIFU). To investigate the effect of these particles on the destruction of tumor
      spheroids using HIFU, HeLa spheroids were insonated in the presence and absence
      of magnetite nanoparticle agglomerates. The HIFU transducer was operated with a
      frequency of 1.1 MHz, pulse repetition frequency of 1.67 kHz, 5% and 50% duty
      cycles and peak negative focal pressure of 7.2 MPa for 10 s. The significant
      increase in the HIFU-induced inertial cavitation caused by the presence of
      magnetite particles at 50% duty cycle was sufficient to cause cell lysis and
      disintegrate the whole spheroid (p <= 0.001). This suggests that magnetite
      nanoparticle agglomerates can enhance the efficacy of HIFU in tumor ablation and
      other related therapies.

PMID- 21084160
TI  - Identifying elderly women with osteoporosis by spinal dual X-ray absorptiometry,
      calcaneal quantitative ultrasound and spinal quantitative computed tomography: a
      comparative study.
AB  - The ability of spinal dual x-ray absorptiometry (DXA), calcaneal quantitative
      ultrasound (QUS) and spinal quantitative computed tomography (QCT) to identify
      women with osteoporosis within the GISELA study was evaluated in 43 women, aged
      62-87 years. Osteoporosis was defined as a T-score below or equal to -2.5 using
      DXA (femoral neck). To determine the performance of each method, the sensitivity,
      specificity and area under the curve (by means of a receiver operating
      characteristic [ROC] analysis) were calculated. The median T-scores from the
      measurements differed significantly (p < 0.0001). DXA (spine) identified 75% of
      women with osteoporosis; QUS and QCT identified 100%. The specificity was 89% for
      DXA (spine), 66% for QUS and 29% for QCT. ROC analysis showed that all three
      methods are qualified to identify women with osteoporosis; however, the different
      sensitivities and specificities of the methods, as well as the thresholds used
      for diagnosing osteoporosis have to be considered.

PMID- 21084161
TI  - Application of bifunctional magnetic adsorbent to adsorb metal cations and
      anionic dyes in aqueous solution.
AB  - A magnetic adsorbent, amine-functionalized silica magnetite
      (NH(2)/SiO(2)/Fe(3)O(4)), has been synthesized to behave as an anionic or
      cationic adsorbent by adjusting the pH value of the aqueous solution to make
      amino groups protonic or neutral. NH(2)/SiO(2)/Fe(3)O(4) were used to adsorb
      copper ions (metal cation) and Reactive Black 5 (RB5, anionic dye) in an aqueous
      solution in a batch system, and the maximum adsorption were found to occur at pH
      5.5 and 3.0, respectively. The adsorption equilibrium data were all fitted the
      Langmuir isotherm equation reasonably well, with a maximum adsorption capacity of
      10.41 mg g(-1) for copper ions and of 217 m g g(-1) for RB5. A pseudo-second
      order model also could best describe the adsorption kinetics, and the derived
      activation energy for copper ions and RB5 were 26.92 kJ mol(-1) and 12.06 kJ mol(
      1), respectively. The optimum conditions to desorb cationic and anionic
      adsorbates from NH(2)/SiO(2)/Fe(3)O(4) were provided by a solution with 0.1M
      HNO(3) for copper ions and with 0.05 M NaOH for RB5.

PMID- 21084162
TI  - Spinal cord stimulation for the treatment of refractory angina pectoris: a
      multicenter randomized single-blind study (the SCS-ITA trial).
AB  - Spinal cord stimulation (SCS) is believed to be effective in treating refractory
      angina. The need for SCS-related chest paresthesia, however, has hitherto made
      impossible placebo-controlled trials. Subliminal (non paresthesic) SCS, however,
      might be also effective on anginal pain. In this trial we compared subliminal SCS
      with paresthesic SCS and with sham SCS. Twenty-five refractory angina patients,
      who had never received SCS before, underwent SCS device implantation and were
      randomized to three groups: paresthesic SCS (group PS; n=10), subliminal SCS
      (group SS; n=7) or "sham" SCS (group NS; n=8). After 1month group NS patients
      were randomized to either group PS or SS. After 1month, changes in angina
      episodes (p=0.016), nitroglycerin use (p=0.015), angina class (p=0.02), quality
      of life score (p=0.05), and items 2 (p=0.008) and 3 (p=0.009) of Seattle angina
      questionnaire differed significantly among groups. Group PS showed significant
      improvement in outcomes compared to group NS, whereas there were no significant
      differences between groups SS and NS; furthermore, only nitroglycerin use
      differed significantly between groups PS and SS. At 3months, a significant
      difference between groups PS and SS was observed in angina attacks (p=0.002), but
      not in other variables. Thus, in this study, paresthesic, but not subliminal SCS
      was superior to sham SCS in improving clinical status in refractory angina
      patients. The lack of significant differences between PS and SS groups in this
      small study suggests that a possible role for subliminal SCS in individual
      patients deserves to be assessed in larger trials with appropriate statistical
      power.

PMID- 21084163
TI  - Aluminium hand splint for postoperative immobilisation of flexion deformity of
      digits and palm: a simple method.

PMID- 21084164
TI  - Burn wound healing time assessed by laser Doppler imaging. Part 2: validation of
      a dedicated colour code for image interpretation.
AB  - INTRODUCTION: Laser Doppler imaging (LDI) has been investigated and used since
      1993 for the assessment of burn wounds. Here we describe tests that validate use
      of the dedicated colour palette, derived in Part 1, for a standardised
      interpretation of LDI images for prediction of healing time (<14 days, 14-21 days
      or >21 days). We also describe clinical and technical factors to be taken into
      account during LDI imaging and during image interpretation. METHODS: (1) A cohort
      of images, selected at random, were assessed, according to strict rules of
      interpretation, by 6 clinicians against photographs of healing, for accuracy of
      healing time prediction and clinical usefulness using five-point scales. (2) All
      images were assessed technically in a similar way for accuracy and the accuracy
      was further studied by analysing the data by ordinal logistic regression to
      predict the dependence of burn healing time on demographic variables (age, sex,
      race, %TBSA, burn cause and site). (3) Where average LDI blood flow could be
      determined, regression analysis was used to assess the potential accuracy of the
      technique. RESULTS: (1) Clinical accuracy was found to be 93% and usefulness was
      89%; (2) technical accuracy was found to be 96%; (3) regression analysis found
      that a potential accuracy of 90.9% could be achieved using LDI results alone,
      increasing to 92% if gender was also considered; no other parameters had an
      influence on healing time prediction. CONCLUSION: LDI can be used in a
      standardised way as a valid tool for improving on clinical assessment of burn
      wounds. This can enable earlier appropriate management.

PMID- 21084165
TI  - Parental alcohol use, alcohol-related problems, and alcohol-specific attitudes,
      alcohol-specific communication, and adolescent excessive alcohol use and alcohol
      related problems: An indirect path model.
AB  - Alcohol-specific parent-child communication has often been studied in relation to
      regular alcohol use of adolescents. However, it might be as important to focus on
      adolescent problematic alcohol use. In addition, the way parents communicate with
      their children about alcohol might depend on their own (problematic) drinking
      behaviors. Therefore, the current study examined the direct effects of parental
      alcohol use, alcohol-related problems, and parental alcohol-specific attitudes on
      adolescent excessive drinking and alcohol-related problems later in life. It also
      looked at indirect effects via alcohol-specific communication. The sample
      consisted of 428 Dutch families including fathers, mothers and adolescents from
      two age groups (13 and 15 years old) at T1, who have been surveyed annually for 5
      years. We tested the model with structural equation modeling (SEM). The results
      showed that parental alcohol-related problems were positively associated with
      communication about alcohol, which in turn was related with less excessive
      adolescent drinking and alcohol-related problems. Lenient parental attitudes
      about alcohol and parental alcohol-related problems were directly related to more
      excessive drinking and alcohol-related problems in adolescents. In conclusion,
      alcohol-specific communication intervenes in the relationship between parental
      alcohol-related problems and adolescent excessive drinking and alcohol-related
      problems. This indicates that in family alcohol interventions targeted at youth
      alcohol use, parental alcohol-related problems should be taken into account.

PMID- 21084166
TI  - Over-expression of has2 in synovium-derived mesenchymal stem cells may prevent
      adhesions following surgery of the digital flexor tendons.
AB  - The prevention of peritendinous adhesions after zone II flexor tendon repair
      poses a significant challenge to hand surgeons. Exogenous hyaluronic acid (HA)
      has been widely studied and has been found to promote tendon healing and decrease
      adhesion formation in digital flexor tendons following surgery. However, the
      clinical application of exogenous HA is restricted due to limitations inherent in
      the exogenously expressed form. However, hyaluronic acid synthase 2 (has2) has
      been shown to promote synthesis of the endogenous high molecular weight HA in
      many cells. Taken together with the fact that synovium-derived mesenchymal stem
      cells (SMSCs) are more proliferative than other MSCs, we hypothesize that over
      expression of has2 in SMSCs will be an effective therapeutic in preventing the
      adhesions in surgery of the digital flexor tendons.

PMID- 21084167
TI  - Host expression of methylmalonyl-CoA mutase and tuberculosis: a missing link?
AB  - Bovine tuberculosis (bTB) is a disease caused by Mycobacterium bovis and closely
      related species of the Mycobacterium tuberculosis complex. bTB is an important
      health problem affecting livestock, wild animals and accounting for up to 10% of
      human TB cases worldwide. Several hypotheses have been considered to explain the
      low incidence of active TB despite high infection rates and the variable response
      to BCG vaccination. These hypotheses have considered genetic factors of immunized
      individuals and BCG strains, sensitization to environmental mycobacteria and
      metabolic processes. However, a link has not been established between genetic
      factors and metabolic processes that may affect the outcome of M. bovis infection
      and response to BCG vaccination. Herein we used published data linking host
      cholesterol metabolism with mycobacterial infection, persistence and disease
      outcome, and results obtained from studies of M. bovis infection and BCG
      vaccination in the wild boar bTB model to propose a hypothesis: host genetically
      defined higher host methylmalonyl-CoA mutase (MUT) expression levels result in
      lower serum cholesterol concentration and tissue deposits that increase the
      protective immune response to M. bovis, thus resulting in resistance to bTB and
      better response to BCG vaccination. If the hypothesis is proven true, these
      results have important implications for the prevention and treatment of bTB in
      humans and for the eradication of bTB in wildlife reservoir hosts.

PMID- 21084168
TI  - Pokkuri Death Syndrome; sudden cardiac death cases without coronary
      atherosclerosis in South Asian young males.
AB  - Sudden death is one of the major concerns in forensic medicine. Especially when
      the deceased is a young subject without significant history, the case will be of
      major interest to the authorities. Sudden unexplained cardiac death has been
      known as "Pokkuri Death Syndrome" (PDS) in Japan, "Lai Tai" in Thailand,
      "Bangungut" in the Philippines, "Dream Disease" in Hawaii, and "Sudden Unexpected
      Nocturnal Death Syndrome" among South Asian immigrants in the USA. However, the
      clinical and pathological features of these sudden death cases, especially the
      characteristics of no coronary atherosclerosis, are surprisingly similar and
      mainly occur among Southeast Asian young males during sleep in the midnight. In
      this manuscript, we have reviewed the pathological characteristics and the
      possible mechanism of death in PDS cases, which were associated with
      significantly elevated remnant lipoproteins in plasma as revealed from our
      studies during the past 15 years in Japan. Although elevated plasma remnant
      lipoproteins have been known to be strongly atherogenic, coronary atherosclerosis
      was not observed in PDS cases. PDS cases were shown to be an interesting
      cardiovascular disease death discovered in forensic medicine research, which may
      suggest the difference between the occurrence of cardiovascular events and the
      severity of coronary atherosclerosis as separate factors. These observations in
      PDS cases suggest the possibility that the intervention could be more targeted to
      suppress the cardiovascular events rather than to slow down the progression of
      atherosclerosis, which is now most extensively targeted for the therapy of
      cardiovascular disease in Western countries.

PMID- 21084169
TI  - A case of successful treatment of a patient with hyperglycemia of 2700 mg/dL.
AB  - A 34-year-old man with obesity who was an avid consumer of soft drinks was found
      in a coma after complaining of a poor physical condition for a few days. On
      arrival, he had hyperglycemia of 2700 mg/dL, coma, shock, sepsis, aspiration
      pneumonia, acute renal failure, acute pancreatitis, liver dysfunction, and
      systemic mycosis. The rapid infusion of a large volume of isotonic saline,
      insulin, antibiotics, and ulinastatin was performed, and mechanical ventilation
      was applied. The treatment was complicated by transient hypernatremia resulting
      from osmostasis, which gradually decreased. He demonstrated transient decerebrate
      posturing upon stimulation; however, he became conscious within a week of
      admission, and his associated diseases also improved. After correcting his
      hyperglycemia, the patient was discharged on foot. We report our case of a
      patient with hyperglycemia of 2700 mg/dL, which was the highest value reported in
      the English literature. During the correction of the hyperglycemia, transient
      hypernatremia occurred to prevent abrupt decrease in osmolality, which thus
      resulted in cell swelling.

PMID- 21084170
TI  - Measuring oral contraceptive knowledge: a review of research findings and
      limitations.
AB  - OBJECTIVE: Poor oral contraceptive (OC) knowledge may contribute to premature OC
      discontinuation and unintended pregnancy. Yet, to understand relationships
      between OC knowledge and contraceptive behavior, knowledge must be adequately
      measured. This review evaluates the findings and methodological limitations of
      research in which OC knowledge has been measured. METHODS: We performed a
      systematic review of primary research from January 1965 to January 2009. Studies
      were audited for study characteristics, purpose for measuring OC knowledge, key
      findings and measurement properties including administration method, knowledge
      domains, reliability, validity, health literacy and cultural sensitivity.
      RESULTS: We reviewed 21 studies: 18 cohort studies, including one psychometric
      evaluation, and three randomized trials. Results on OC knowledge outcomes were
      variable. Measures were largely self-administered survey (n=15) and lacked
      assessment of all OC knowledge domains. Information on measures' characteristics,
      reliability, validity, health literacy and cultural sensitivity was limited.
      CONCLUSION: Existing OC knowledge measures lack critical psychometric elements,
      leading to inconsistent and unreliable findings. PRACTICE IMPLICATIONS: Poor OC
      knowledge measurement precludes identifying counseling needs and developing
      interventions for contraceptive behavior change. Future research considerations
      include: measurement information in publications, psychometric evaluations,
      formal reliability/validity techniques, and attention to all OC knowledge
      domains, health literacy and cultural sensitivity.

PMID- 21084171
TI  - Epilepsy and intellectual disability: does epilepsy increase the likelihood of co
      morbid psychopathology?
AB  - Although epilepsy is particularly common among people with intellectual
      disability (ID) it remains unclear whether it is associated with an increased
      likelihood of co-morbid psychopathology. We therefore investigated rates of
      mental health problems and other clinical characteristics in patients with ID and
      epilepsy (N = 156) as compared to patients with ID but no epilepsy (N = 596). All
      participants were consecutive referrals to specialist mental heath services.
      Specialist clinicians agreed on the mental health diagnoses by applying ICD-10
      clinical criteria using information gained from interviews with key informants
      and the patients. Bivariate and multivariate analyses showed that patients with
      epilepsy were more likely to live in residential housing and have severe ID in
      line with previous evidence. However, the presence of epilepsy was not associated
      with an increased likelihood of co-morbid psychopathology. On the contrary, rates
      of mental health problems, including schizophrenia spectrum, personality and
      anxiety disorders, were significantly lower among patients with epilepsy. The
      results are discussed in the context of mood-stabilizing and other psychotropic
      effects of anti-epileptic drugs in adults with ID and epilepsy, as well as
      possible diagnostic overshadowing.

PMID- 21084172
TI  - Route learning and shortcut performance in adults with intellectual disability: a
      study with virtual environments.
AB  - The ability to learn routes though a virtual environment (VE) and to make a novel
      shortcut between two locations was assessed in 18 adults with intellectual
      disability and 18 adults without intellectual disability matched on chronological
      age. Participants explored two routes (A <=> B and A <=> C) until they reached a
      learning criterion. Then, they were placed at B and were asked to find the
      shortest way to C (B <=> C, five trials). Participants in both groups could learn
      the routes, but most of the participants with intellectual disability could not
      find the shortest route between B and C. However, the results also revealed
      important individual differences within the intellectual disability group, with
      some participants exhibiting more efficient wayfinding behaviour than others.
      Individuals with intellectual disability may differ in the kind of spatial
      knowledge they extract from the environment and/or in the strategy they use to
      learn routes.

PMID- 21084173
TI  - Miniplate osteosynthesis with four different systems in sheep.
AB  - The aim of this study was to compare a combination of a locking system with self
      tapping (ST-L) or self-drilling-tapping (SDT-L) screws with a combination of
      conventional miniplates with self-tapping (ST) and self-forming (SF) screws. A
      standardized osteotomy and osteosynthesis with one of the above mentioned systems
      was performed in 24 sheep. Callus formation was measured with the help of CT
      scans assisted by a navigation system. Specimens of each osteotomy gap were taken
      and examined histologically. The best results were observed when self-tapping
      screws and the Mini-Locking-System (ST-L) were applied. The slowest healing was
      seen in animals treated with miniplates and SF screws. After 8 weeks an increase
      in bone formation could be observed in the ST, SF, SDT-L systems. The results
      after 8 weeks were comparable with those achieved by the ST-L system after 4
      weeks. The improved stability of the osteosynthesis with the ST-L system resulted
      in early ossification of the osteotomy gap and the smallest amount of callus
      formation.

PMID- 21084174
TI  - Effect of icariin on bone formation during distraction osteogenesis in the rabbit
      mandible.
AB  - The aim of this study was to evaluate the effect of icariin on bone formation
      during mandibular distraction. 40 Rabbits were randomly divided into experimental
      and control groups. Mandibular distraction was performed 5 days after unilateral
      mandibular osteotomy using a custom-made external distractor at a rate of
      0.5mm/12h for 10 days. From the first day of distraction, icariin (2.5mg/kg .
      day) was orally administered to the experimental group and placebo to the
      controls. 10 Rabbits were killed at the end of weeks 2 and 4 of the consolidation
      phase. The distracted hemimandible was harvested and newly formed bone was
      evaluated by soft radiography, histology and bone histomorphometry. Regenerated
      bone was evaluated for bone mineral density by dual-energy X-ray absorptiometry.
      The experimental group had fewer radiolucent areas on soft radiography. Bone
      mineral density of regenerated bone was higher in the experimental than in the
      control group at 2 and 4 weeks. At 4 weeks, the experimental group had greater
      volumes of new bone, higher trabecular number, and less trabecular separation
      than the controls. Oral administration of icariin could promote bone formation
      during mandibular distraction osteogenesis and might be a promising method for
      shortening the course of distraction osteogenesis.

PMID- 21084175
TI  - Recent trends in primary antimicrobial resistance of Helicobacter pylori in
      Finland.
AB  - The antimicrobial susceptibility of Helicobacter pylori is an important predictor
      of the success of eradication therapy. To evaluate recent changes in primary
      antimicrobial resistance of H. pylori isolated from Finnish patients, the
      clinical records of H. pylori-positive patients referred for endoscopy to
      Herttoniemi Hospital (Helsinki, Finland) during 2000-2008 were investigated
      retrospectively. Stored H. pylori strains from 505 patients without previous
      eradication therapy were tested for clarithromycin, metronidazole, levofloxacin,
      tetracycline and amoxicillin susceptibility by Etest. Data on local consumption
      of antimicrobials were collected and correlations between consumption and
      resistance were calculated. During the 9-year study period, metronidazole
      resistance was high (range 29-59%, overall 41%). After an initial increase in
      clarithromycin resistance (0% in 2000 to 16% in 2003), resistance to
      clarithromycin decreased to 4% in 2008. No significant correlation was detected
      between consumption of macrolides and resistance of clarithromycin. Resistance to
      levofloxacin varied between 0% and 12%. Primary metronidazole resistance in H.
      pylori is at a high level, however levofloxacin and clarithromycin resistances
      are still at a reasonable level. Thus, primary clarithromycin resistance in H.
      pylori in Finland has not become such a problem as in many other countries.
      Primary resistance to the antimicrobials studied varied considerably from year to
      year.

PMID- 21084176
TI  - Insomnia medication: do published studies reflect the complete picture of
      efficacy and safety?
AB  - Selective publication can have a deleterious effect on evidence based medicine,
      health policy decision making and treatment guidelines. Using the European Public
      Assessment Reports (EPARs) as reference, this study examined selective
      publication and selective reporting of efficacy and safety of insomnia
      medication. EPARs of with three insomnia medications were used to identify all
      clinical trials that were performed between 1998 and 2007 for the purpose of
      registration in the EU. The matching publication for each trial was searched
      through a systematic literature search. Accuracy of information in the
      publications was examined by comparison to the information in the EPARs. Only 55%
      of the trials with insomnia medications identified in EPARs were published.
      Positive trials were approximately two times more likely to be published. The lag
      time from study completion to publication was shorter for the positive compared
      to the negative trials. Sample size did not correlate with publication of
      negative trials. The meta-analysis of the effect size of insomnia medication was
      1.6 times larger in the published data compared to the complete data. While the
      primary end points of the trials were reported reliably in the publications,
      remarkable inconsistencies were detected in the reporting of the secondary end
      points, methods, results and, especially safety. In conclusion, selective
      publication and reporting lead to an overestimation of efficacy and
      underestimation of safety of insomnia products. Authors of treatment guidelines
      should be aware of this bias. EPARs/FDA reviews provide a more unbiased view of
      the benefit-risk balance of insomnia and other medications and hence these
      documents should be consulted by e.g. authors of meta-analyses and of treatment
      guidelines.

PMID- 21084177
TI  - [Recurrent and metastatic infantile fibrosarcoma: a case report].
AB  - Infantile fibrosarcoma is a rare malignant tumor that usually occurs during the
      1st year of life. It accounts for approximately 5-10% of all sarcomas in infants
      younger than 1 year of age. It usually has indolent progression and metastatic
      spread is rare. We report the case of a patient who had infantile fibrosarcoma of
      the trunk. At birth, the baby presented a soft tissue mass of the scapulothoracic
      region. Histopathological examination after complete surgical resection at first
      suggested an angioma. Reanalysis of the histology after a metastatic relapse
      resulted in the diagnosis of infantile fibrosarcoma, which was confirmed by the
      presence of the specific translocation seen in infantile fibrosarcoma
      (ETV6/NTRK3). This patient's progression was uncommon because he developed 3
      metastatic relapses. The treatment consisted of surgery, chemotherapy, and
      radiation therapy. The patient is alive with persistent complete remission. We
      discuss the diagnostic and therapeutic issues of infantile fibrosarcoma. There is
      a risk of erroneous diagnosis in newborn infants between benign angiomatous tumor
      and infantile fibrosarcoma. The fusion transcript ETV6-NTRK3 resulting from the
      specific chromosomal translocation t(12;15)(p13;q25) is now a useful diagnostic
      tool for infantile fibrosarcoma. Surgery with wide resection is the mainstay of
      treatment. However, infantile fibrosarcoma is a chemosensitive tumor. If initial
      surgery cannot be done without mutilation or is impossible, preoperative
      chemotherapy should be given. The role of radiation therapy is still debated.

PMID- 21084178
TI  - Exploiting the systematic review protocol for classification of medical
      abstracts.
AB  - OBJECTIVE: To determine whether the automatic classification of documents can be
      useful in systematic reviews on medical topics, and specifically if the
      performance of the automatic classification can be enhanced by using the
      particular protocol of questions employed by the human reviewers to create
      multiple classifiers. METHODS AND MATERIALS: The test collection is the data used
      in large-scale systematic review on the topic of the dissemination strategy of
      health care services for elderly people. From a group of 47,274 abstracts marked
      by human reviewers to be included in or excluded from further screening, we
      randomly selected 20,000 as a training set, with the remaining 27,274 becoming a
      separate test set. As a machine learning algorithm we used complement naive
      Bayes. We tested both a global classification method, where a single classifier
      is trained on instances of abstracts and their classification (i.e., included or
      excluded), and a novel per-question classification method that trains multiple
      classifiers for each abstract, exploiting the specific protocol (questions) of
      the systematic review. For the per-question method we tested four ways of
      combining the results of the classifiers trained for the individual questions. As
      evaluation measures, we calculated precision and recall for several settings of
      the two methods. It is most important not to exclude any relevant documents
      (i.e., to attain high recall for the class of interest) but also desirable to
      exclude most of the non-relevant documents (i.e., to attain high precision on the
      class of interest) in order to reduce human workload. RESULTS: For the global
      method, the highest recall was 67.8% and the highest precision was 37.9%. For the
      per-question method, the highest recall was 99.2%, and the highest precision was
      63%. The human-machine workflow proposed in this paper achieved a recall value of
      99.6%, and a precision value of 17.8%. CONCLUSION: The per-question method that
      combines classifiers following the specific protocol of the review leads to
      better results than the global method in terms of recall. Because neither method
      is efficient enough to classify abstracts reliably by itself, the technology
      should be applied in a semi-automatic way, with a human expert still involved.
      When the workflow includes one human expert and the trained automatic classifier,
      recall improves to an acceptable level, showing that automatic classification
      techniques can reduce the human workload in the process of building a systematic
      review.

PMID- 21084179
TI  - Lymph node growth rate in testicular germ cell tumours: implications for computed
      tomography surveillance frequency.
AB  - AIM: To estimate the growth rate of lymph nodes in patients on surveillance for
      testicular cancer who developed recurrent disease. MATERIALS AND METHODS: During
      a 7-year period, 318 patients at our institution were managed by surveillance and
      39 relapsed (12.3%). The computed tomography scans of 28 patients (median age 32
      years; range 19-51 years) who met our inclusion criteria and who developed
      recurrent disease in the abdomen/pelvis were retrospectively reviewed. Thirteen
      patients had non-seminoma and 15 had seminoma. To estimate the lymph node growth
      rate, the slope of lymph node size over time was calculated. RESULTS: The median
      length of time from orchiectomy to the recurrence computed tomography was 131
      days (range 49-520) or about 4.4 months for non-seminoma patients and 373 days
      (range 129-675) or about 12.3 months for seminoma patients. The median size of
      the involved lymph node at final computed tomography for seminoma patients was 12
      mm (range 9-31 mm) and for non-seminoma patients was 15 mm (range 10-56 mm). The
      median lymph node growth rate for patients with seminoma was 1.35 mm/month (range
      0.62-4.56) and for patients with non-seminoma 2.99 mm/month (range 0.77-7.06);
      the difference in growth rates was statistically significant (P=0.029).
      CONCLUSIONS: There is a statistically significant faster growth rate of lymph
      nodes in patients with recurrent non-seminoma compared with patients with
      seminoma. This finding supports a more frequent computed tomography schedule
      during the first 2 years of surveillance in non-seminoma patients compared with
      seminoma patients.

PMID- 21084180
TI  - NMR-determined lipoprotein subclass profile is associated with dietary
      composition and body size.
AB  - BACKGROUND AND AIMS: Dyslipidemia is influenced by diet and body habitus. The
      Nuclear Magnetic Resonance spectroscopy lipoprotein subclass profile (NMR-LSP) is
      associated with diabetes and its vascular complications; and an NMR-LSP featuring
      large VLDL particles and small LDL and HDL particles is linked with
      cardiovascular disease (CVD). Thus interventions which favourably modify NMR-LSP
      may reduce risk for diabetes, its complications and CVD. The study aim was to
      investigate the associations between NMR-LSP, dietary composition and body size
      measures using data from the Melbourne Collaborative Cohort Study (MCCS). METHODS
      AND RESULTS: NMR-LSP was assessed in 313 men and 403 women (median age 54 years)
      randomly selected from a community-based cohort study. Diet was assessed using a
      specifically developed food frequency questionnaire (FFQ), and body size was
      assessed by body mass index (BMI) or waist:hips ratio (WHR). To simplify the 15
      NMR-LSP variables, factor analysis was used to derive a single factor.
      Multivariate linear regression with this factor score as the dependent variable
      demonstrated that in men, total PUFA and n-6 dietary fat intake and BMI were
      associated with a more atherogenic NMR-LSP pattern; while in women dietary
      glycemic index and WHR demonstrated positive associations, and n-3 fat intake an
      inverse association. CONCLUSIONS: We developed a single factor score to summarize
      the NMR-LSP that has the benefit of combining all aspects of the NMR-LSP and
      accounting for correlations between them. We have shown correlations between the
      NMR-LSP and body size and dietary composition.

PMID- 21084181
TI  - The novel antidote Bezoar Bovis prevents the cardiotoxicity of Toad (Bufo bufo
      gargarizans Canto) Venom in mice.
AB  - Toad Venom, called chansu (CS) in China, is an anti-inflammatory drug used in
      small doses for the treatment of various types of inflammation in China. Its use
      is hampered by the cardiotoxicity of bufadienolides derived from Toad Venom.
      Bezoar Bovis is another frequently used drug in Toad Venom preparations for the
      treatment of inflammatory or cardiovascular diseases in Asia. We explored whether
      Bezoar Bovis could protect against CS-induced acute toxicity in mice. Toxicity
      was assessed by the general features of poisoning, electrocardiography (ECG), and
      levels of creatine kinase (CK), lactate dehydrogenase (LDH) and calcium ions
      (Ca(2+)) in cardiac tissues. Toad Venom (90 mg/kg) caused opisthotonus,
      ventricular arrhythmias, and increases in cardiac levels of Ca(2+), CK and LDH.
      Pretreatment with Bezoar Bovis (120, 240 and 480 mg/kg) significantly reduced the
      prevalence of opisthotonus and mortality, and prevented cardiotoxicity in CS
      treated mice as evidenced by decreases in the scores of arrhythmias and cardiac
      levels of CK, LDH and Ca(2+). Furthermore, the bilirubin, and taurine derived
      from Bezoar Bovis offered marked protection against the arrhythmias induced by CS
      or bufalin in vivo and in vitro. An anti-inflammatory study showed that Bezoar
      Bovis did not compromise the anti-inflammatory activity of Toad Venom on
      concanavalin-A (ConA)-stimulated proliferation of human peripheral blood
      mononuclear cells. These results suggested that Bezoar Bovis elicited protective
      and anti-arrhythmic effects against Toad Venom intoxication in mice, and is a
      novel antidote in combination with Toad Venom therapy.

PMID- 21084182
TI  - Effects of surface functionalization on the surface phage coverage and the
      subsequent performance of phage-immobilized magnetoelastic biosensors.
AB  - One of the important applications for which phage-immobilized magnetoelastic (ME)
      biosensors are being developed is the wireless, on-site detection of pathogenic
      bacteria for food safety and bio-security. Until now, such biosensors have been
      constructed by immobilizing a landscape phage probe on gold-coated ME resonators
      via physical adsorption. Although the physical adsorption method is simple, the
      immobilization stability and surface coverage of phage probes on differently
      functionalized sensor surfaces need to be evaluated as a potential way to enhance
      the detection capabilities of the biosensors. As a model study, a filamentous fd
      tet phage that specifically binds streptavidin was adsorbed on either bare or
      surface-functionalized gold-coated ME resonators. The surface functionalization
      was performed through the formation of three self-assembled monolayers with a
      different terminator, based on the sulfur-gold chemistry: AC (activated carboxy
      terminated), ALD (aldehyde-terminated), and MT (methyl-terminated). The results,
      obtained by atomic force microscopy, showed that surface functionalization has a
      large effect on the surface phage coverage (46.8%, 49.4%, 4.2%, and 5.2% for
      bare, AC-, ALD-, and MT-functionalized resonators, respectively). In addition, a
      direct correlation of the observed surface phage coverage with the quantity of
      subsequently captured streptavidin-coated microbeads was found by scanning
      electron microscopy and by resonance frequency measurements of the biosensors.
      The differences in surface phage coverage on the differently functionalized
      surfaces may then be used to pattern the phage probe layer onto desired parts of
      the sensor surface to enhance the detection capabilities of ME biosensors.

PMID- 21084183
TI  - Relationship between sun exposure and melanoma risk for tumours in different body
      sites in a large case-control study in a temperate climate.
AB  - AIM: A melanoma case-control study was conducted to elucidate the complex
      relationship between sun exposure and risk. METHODS: Nine hundred and sixty
      population-ascertained cases, 513 population and 174 sibling controls recruited
      in England provided detailed sun exposure and phenotype data; a subset provided
      serum 25-hydroxyvitamin D(2)+D(3) levels. RESULTS: Phenotypes associated with a
      tendency to sunburn and reported sunburn at >= 20 years of age were associated
      with increased melanoma risk (odds ratio (OR) 1.56, 95% confidence intervals (CI)
      1.23-1.99). Holiday sun exposure was not associated with an increased melanoma
      risk although this may be in part because reported sun exposure overall was much
      lower in those with a sun-sensitive phenotype, particularly among controls. Head
      and neck melanoma was associated with less sun exposure on holidays at low
      latitudes (OR 0.39, 95% CI (0.23-0.68) for >13 h/year compared to <3.1). Overall
      the clearest relationship between reported sun exposure and risk was for average
      weekend sun exposure in warmer months, which was protective (OR 0.67, 95% CI 0.50
      0.89 for highest versus lowest tertile of exposure). Serum vitamin D levels were
      strongly associated with increased weekend and holiday sun exposure. CONCLUSIONS:
      Sun-sensitive phenotypes and reported sunburn were associated with an increased
      risk of melanoma. Although no evidence was seen of a causal relationship between
      holiday sun exposure and increased risk, this is consistent with the view that
      intense sun exposure is causal for melanoma in those prone to sunburn. A
      protective effect of regular weekend sun exposure was seen, particularly for limb
      tumours, which could be mediated by photoadaptation or higher vitamin D levels.

PMID- 21084184
TI  - Is concurrent radiation therapy required in patients receiving preoperative
      chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial.
AB  - INTRODUCTION: Preoperative chemotherapy (CT) and preoperative chemoradiation
      therapy (CRT) for resectable oesophageal cancer have been shown to improve
      overall survival in meta-analyses. There are limited data comparing these
      preoperative therapies. We report the outcomes of a randomised phase II trial
      comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus
      and gastro-oesophageal junction. METHODS: Patients were randomised to receive
      preoperative CT with cisplatin (80 mg/m(2)) and infusional 5 fluorouracil (1000
      mg/m(2)/d) on days 1 and 21, or preoperative CRT with the same drugs accompanied
      by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5
      fluorouracil reduced to 800 mg/m(2)/d. The radiation dose was 35 Gy in 15
      fractions over 3 weeks. The endpoints were toxicity, response rates, resection
      (R) status, progression-free survival (PFS), overall survival (OS) and quality of
      life. RESULTS: Seventy-five patients were enrolled on the study: 36 received
      preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT.
      Eight patients (11%) did not proceed to resection. The histopathological response
      rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT
      11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months
      for CT and CRT respectively (p = 0.37). The median OS was 29 months for CT
      compared with 32 months for CRT (p = 0.83). CONCLUSIONS: Despite no difference in
      survival, the improvement from preoperative CRT with respect to margin
      involvement makes this treatment a reasonable option for bulky, locally advanced
      resectable adenocarcinoma of the oesophagus.

PMID- 21084185
TI  - Methane emissions from a full-scale A/A/O wastewater treatment plant.
AB  - Methane (CH(4)) emissions from a full-scale anaerobic/anoxic/oxic (A/A/O)
      wastewater treatment plant (WWTP) (Jinan, China) were investigated during spring
      and summer of 2010. Results showed that the major emission sources of CH(4)
      performed the following descending order: anaerobic tanks, oxic tanks, aerated
      grit chambers and sludge concentration tanks. The total annual fluxes of CH(4)
      emissions from the Jinan WWTP were 1.69 * 10(4)kg yr(-1), with the emission
      factors of per capita emissions of 11.3g CH(4) person(-1)yr(-1) and flow-based
      emissions of 1.55 * 10(-4)g CH(4) (L of wastewater)(-1). The estimated source
      strength of methane for all WWTPs in China was 6.2 Gg yr(-1) (1 Gg=10(9)g). The
      most significant factors influencing methane emissions were dissolved oxygen
      concentration in aerated grit chamber and oxic tank and water temperature in high
      density settler tanks.

PMID- 21084186
TI  - Air sampling methods for VOCs related to field-scale biosecure swine mortality
      composting.
AB  - Monitoring specific volatile organic compounds (VOCs) as markers of biosecure
      carcass degradation is a promising method to test progress and completion of the
      composting process. The objective of this study was to test the feasibility of
      using existing aeration ducts in composting units as practical sampling
      locations. The secondary objective was to test the feasibility of using marker
      VOC concentrations in aeration ducts to elucidate information about airflow
      patterns inside composting units. Marker VOC concentrations were significantly
      higher in the upper aeration duct and this duct can typically be used to collect
      air samples instead of placing special air sampling probes inside the composting
      units. Occasionally, the airflow direction inside composting units can change.
      Marker VOC concentrations can be used to decide the airflow direction inside the
      composting units. In this study, higher VOC concentrations were measured from the
      upper aeration duct, and this duct was shown to be an outlet.

PMID- 21084187
TI  - Synthesis and antibacterial activity of novel 4-aryl-[1,2,3]-triazole containing
      macrolides.
AB  - Two series of novel triazole containing 14-member macrolides having either a
      cladinose or a 3-pyridyl acetate group at the 3-position of the macrolide ring
      were synthesized. The in vitro antibacterial activities against S. aureus, S.
      pneumoniae, S. pyogenes and E. faecalis were determined. Macrolide 7a and the
      fluoroketolide 1 (CEM-101) were evaluated in vivo in murine systemic infection
      models. All of the macrolide analogs were less active in vitro and in vivo than
      the fluoroketolide 1 (CEM-101).

PMID- 21084188
TI  - Design and an efficient synthesis of natural product-based cyclopenta[b]pyran
      derivatives with potential bioactivity.
AB  - A series of 4-aryl-cyclopenta[b]pyran derivatives, designed based on natural
      product scaffold, were synthesized efficiently via multi-component reaction under
      solvent-free and catalyst-free conditions. This chemistry provides a new compound
      library with potential activity for biomedical screening.

PMID- 21084189
TI  - Click chemistry inspired one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
      and their Src kinase inhibitory activity.
AB  - Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot
      reaction of alpha-tosyloxy ketones/alpha-halo ketones, sodium azide, and terminal
      alkynes in the presence of aq PEG (1:1, v/v) using the click chemistry approach
      and evaluated for Src kinase inhibitory activity. Structure-activity relationship
      analysis demonstrated that insertion of C(6)H(5)- and 4-CH(3)C(6)H(4)- at
      position 4 for both classes and less bulkier aromatic group at position 1 in
      class 1 contribute critically to the modest Src inhibition activity (IC(50) = 32
      43 MUM) of 1,4-disubstituted 1,2,3-triazoles.

PMID- 21084190
TI  - Triterpene derivatives that inhibit human immunodeficiency virus type 1
      replication.
AB  - Triterpene derivatives were analyzed for anti-HIV-1 activity and for cellular
      toxicity. Betulinic aldehyde, betulinic nitrile, and morolic acid derivatives
      were identified to have anti-HIV-1 activity. These derivatives inhibit a late
      step in virus replication, likely virus maturation.

PMID- 21084191
TI  - Chromanol derivatives--a novel class of CETP inhibitors.
AB  - Based on our former development candidate BAY 38-1315, optimization efforts led
      to the discovery of a novel chemical class of orally active cholesteryl ester
      transfer protein (CETP) inhibitors. The chromanol derivative 19b is a highly
      potent CETP inhibitor with favorable pharmacokinetic properties suitable for
      clinical studies. Chemical process optimization furnished a robust synthesis for
      a kilogram-scale process.

PMID- 21084192
TI  - Synthesis and biological activity of pyridopyridazin-6-one p38 MAP kinase
      inhibitors. Part 1.
AB  - The development and synthesis of potent p38alpha MAP kinase inhibitors containing
      a pyridazinone platform is described. Evolution of the p38alpha selective
      pyridopyridazin-6-one series from the p38alpha/beta dual inhibitor 2H-quinolizin
      2-one series will be discussed in full detail.

PMID- 21084193
TI  - CoMFA and CoMSIA studies on 5-hydroxyindole-3-carboxylate derivatives as 5
      lipoxygenase inhibitors: generation of homology model and docking studies.
AB  - In this study, comparative molecular field analysis (CoMFA) and comparative
      molecular similarity indices analysis (CoMSIA) were performed on a series of 2
      substituted 5-hydroxyindole-3-carboxylate derivatives as potent 5-LOX inhibitors
      with IC(50) values ranging from 0.031 to 13.4 MUM. Two datasets of same molecules
      were prepared with two different partial atomic charges; one with Gasteiger
      Huckel and another with the ESPFIT charges obtained from the gaussian package.
      CoMFA and CoMSIA models were generated for both the datasets and the results were
      analysed. With regard to the non-cross validated r(2) values (r(ncv)(2)) and
      cross-validated q(2) values (q(cv)(2)) of the resulting QSAR models, the dataset
      with ESPFIT charges yielded higher values; hence it was further used in the
      study. The CoMFA and CoMSIA models have been further validated for their
      stability and robustness using group validation and bootstrapping techniques and
      for their predictive abilities using an external test set of ten compounds. The
      predictive power of the CoMSIA model was higher than the CoMFA model, the high
      predictive r(2) values of the test set reveals that the models prove to be useful
      tools for activity prediction of newly designed 5-LOX inhibitors. The ESPFIT
      derived charges yielded better models than those based on charges calculated from
      Gasteiger-Huckel charges. We generated a homology model for human 5-LOX and
      identified the key residues at the binding site. The 3D-QSAR models were compared
      with the interactions at the active site to further elucidate the accuracy of the
      models. The data generated from 3D-QSAR study was used to design potential 5-LOX
      inhibitors.

PMID- 21084194
TI  - Identification of novel pyrrolopyrazoles as protein kinase C beta II inhibitors.
AB  - A novel series of pyrrolopyrazole-based protein kinase C beta II inhibitors has
      been identified from high-throughput screening. Herein, we report our initial
      structure-activity relationship studies with a focus on optimizing compound
      ligand efficiency and physicochemical properties, which has led to potent
      inhibitors with good cell permeability.

PMID- 21084195
TI  - Identifying gait events without a force plate during running: a comparison of
      methods.
AB  - This paper presents a comparison of four different methods of identifying the
      times of foot-strike and toe-off during running based on gait marker
      trajectories. The event times predicted by the methods were compared to those
      identified using a force plate for both over-ground and treadmill running. The
      effect of using different threshold values for the detection of gait events using
      force plate data was also investigated, and as a result, all assessments of event
      detection accuracy were based on a cut-off value of 10N. The most accurate method
      of foot-strike detection depended on whether the runner landed with a rear- or a
      mid-foot strike. For rear-foot-strike running, the best method of identifying
      foot-strike used the vertical acceleration profile of the posterior heel distal
      marker and the vertical position profile of the hallux marker. For mid-foot
      strike running, the best method of identifying foot-strike used the vertical
      velocity profile of the mean positions of the posterior heel distal marker and a
      marker midway between the second and third metatarsal heads. The most accurate
      method of identifying toe-off did not depend on type of foot-strike and was based
      on the vertical acceleration and position profiles of the hallux marker.

PMID- 21084196
TI  - abeo-abietanes from Teucrium polium roots as protective factors against oxidative
      stress.
AB  - Six new 17(15->16)-abeo-abietanes, along with seven known compounds, were
      isolated and characterized from ethyl acetate root extract of Teucrium polium L.,
      a medicinal plant belonging to the Labiatae family reported to have
      hypolipidemic, hypoglycaemic, anti-nociceptive and anti-inflammatory effects.
      Their structures were elucidated by 1D ((1)H, (13)C and DEPT) and 2D (COSY,
      TOCSY, HSQC, HMBC, and NOESY) NMR and mass spectral data. The antioxidative
      properties of pure metabolites were analyzed on the basis of their DPPH radical
      scavenging capability. The antioxidant capacity in cell-free systems of the
      isolated metabolites was carried out by measuring their capabilities to inhibit
      the synthesis of thiobarbituric acid reactive species in assay media using as
      oxidable substrates a vegetable fat and the pentose sugar 2-deoxyribose and to
      prevent oxidative damage of the bovine serum albumin (BSA) hydrosoluble protein.
      All of the compounds showed a significant and dose-response efficacy although
      weaker than that exercised by the standard Trolox(r).

PMID- 21084197
TI  - Thermodynamic and NMR analysis of inhibitor binding to dihydrofolate reductase.
AB  - Isothermal titration calorimetry (ITC) was used to determine the thermodynamic
      driving force for inhibitor binding to the enzyme dihydrofolate reductase (DHFR)
      from Escherichia coli. 1,4-Bis-{[N-(1-imino-1-guanidino-methyl)]sulfanylmethyl}
      3,6-dimethyl-benzene (1) binds DHFR:NADPH with a K(d) of 13+/-5 nM while the
      related inhibitor 1-{[N-(1-imino-guanidino-methyl)]sulfanylmethyl}-3
      trifluoromethyl-benzene (2) binds DHFR:NADPH with a K(d) of 3.2+/-2.2 MUM. The
      binding of these inhibitors has both a favorable entropy and enthalpy of binding.
      Additionally, we observe positive binding cooperativity between both 1 and 2 and
      the cofactor NADPH. Binding of compound 1 to DHFR is 285-fold tighter in the
      presence of the NADPH cofactor than in its absence. We did not detect binding of
      2 to DHFR in the absence of NADPH. The backbone amide (1)H and (15)N NMR
      resonances of DHFR:NADPH and both DHFR:NADPH inhibitor complexes were assigned in
      order to better understand the binding of these inhibitors in solution. The
      chemical shift perturbations observed with the binding of 1 were greatest at
      residues closest to the binding site, but significant perturbations also occur
      away from the inhibitor location at amino acids in the vicinity of residue 58 and
      in the GH loop. The pattern of chemical shift changes observed with the binding
      of 2 is similar to that seen with 1. The main differences in chemical shift
      perturbation between the two inhibitors are in the Met20 loop and in residues at
      the interface between the inhibitor and NADPH.

PMID- 21084198
TI  - Outcome of lung transplantation in elderly recipients.
AB  - OBJECTIVE: Lung transplantation is a standard treatment option for patients with
      end-stage lung disease. Lung transplantation in the elderly is controversial due
      to concerns over anticipated increased surgical risks, inferior long-term
      outcomes and proper stewardship in allocating limited donor organs. With
      demographic trends showing an increasing proportion of patients over 60 years
      old, we evaluated our outcomes with lung transplantation in this older cohort.
      METHODS: Between January 1990 and July 2009, 142 patients underwent lung
      transplantation at our institution. A total of 15 patients receiving heart/lung
      transplantation and one patient declining research participation were excluded.
      As many as 126 patients were analyzed in two groups: <60 and >= 60 years old.
      RESULTS: There were 65 females (52%) and 61 males (48%). A total of 53 patients
      (42%) underwent bilateral sequential lung transplantation and 73 patients single
      lung transplantation (58%). Median age at transplantation was 55.3 years (range,
      21.6-73.1 years) with 94 patients <60 years (75%) and 32 patients >= 60 years
      (25%). Median follow-up was 4.3 years (range, 0-17.8 years). Overall survival at
      30 days was 93.7% with no difference between age groups (p=0.95). There was no
      difference between the groups for in-hospital, postoperative complications
      (p=0.86), or unplanned readmission rates within 90 days of the hospitalization
      (p=0.26). Postoperative pulmonary function (forced expiratory volume in 1s (FEV1)
      % predicted) at transplant, 4 weeks, 3 months, and 6 months after transplantation
      was not different between groups (p=0.93). No difference in long-term survival
      was observed (p=0.59), with 5-year survival of 52.2% for patients <60 years and
      47.3% for patients >= 60 years. Overall, 20 patients developed bronchiolitis
      obliterans syndrome and 13 posttransplant lymphoproliferative disease, which was
      not statistically different between age groups (p=0.87, p=0.37, respectively).
      CONCLUSION: Increased age of 60 years and greater, in highly selected patients,
      does not appear to have a significant impact on the short- or long-term outcome
      in patients undergoing lung transplantation. Judicious selection of older
      patients, who are otherwise excellent candidates for lung transplantation,
      remains a reasonable option.

PMID- 21084199
TI  - Depletion of CXCR2 inhibits gamma-secretase activity and amyloid-beta production
      in a murine model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that leads to
      progressive cognitive decline. Recent studies from our group and others have
      suggested that certain G-protein coupled receptors (GPCRs) can influence the
      processing of the amyloid precursor protein (APP). Earlier, we demonstrated that
      stimulation of a chemokine receptor, CXCR2, results in enhanced gamma-secretase
      activity and in increased amyloid-beta (Abeta) production. Taken together,
      results obtained from in vitro studies indicate that therapeutic targeting of
      CXCR2 might aid in lowering Abeta levels in the AD brain. To better understand
      the precise function and to predict the consequences of CXCR2 depletion in the AD
      brain, we have crossed CXCR2 knockout mice with mice expressing presenilin (PS1
      M146L) and APPsw mutations (PSAPP). Our present study confirms that CXCR2
      depletion results in reduction of Abeta with concurrent increases of gamma
      secretase substrates. At the mechanistic level, the effect of CXCR2 on gamma
      secretase was not found to occur via their direct interaction. Furthermore, we
      provide evidence that Abeta promotes endocytosis of CXCR2 via increasing levels
      of CXCR2 ligands. In conclusion, our current study confirms the regulatory role
      of CXCR2 in APP processing, and poses it as a potential target for developing
      novel therapeutics for intervention in AD.

PMID- 21084200
TI  - Effects of repeated Achilles tendon vibration on triceps surae stiffness and
      reflex excitability.
AB  - Clinical studies frequently report an increase in stiffness and a loss of range
      of motion at joints placed in disuse or immobilization. This is notably the case
      for subjects maintained in bed for a long period, whilst their joints are not
      affected. Recently we documented on healthy subjects the benefit in terms of
      force and activation capacities of the triceps surae offered by vibrations
      applied to the Achilles tendon. Knowing that stiffness changes may contribute to
      force changes, the aim of the present study was to investigate the effects of
      tendon vibration on the triceps surae stiffness of healthy subjects. The
      vibration program consisted in 14 days of 1h daily Achilles tendon vibration
      applied at rest. Nineteen healthy students were involved in this study. Before
      and at the end of the vibration program, musculo-tendinous stiffness in active
      conditions was determined by use of a quick-release test. Passive stiffness was
      also analyzed by a flexibility test: passive torque-angle relationships were
      established from maximal plantar-flexion to maximal dorsiflexion. Passive
      stiffness indexes at 10 degrees , 15 degrees  and 20 degrees  dorsiflexion were
      defined as the slope of the relationships at the corresponding angle. Tendinous
      reflex, influenced by stiffness values, was also investigated as well as the H
      reflex to obtain an index of the central reflex excitability. After the program,
      musculo-tendinous stiffness was significantly decreased (p=.01). At the same
      time, maximal passive dorsiflexion was increased (p=.005) and passive stiffness
      indexes at 10 degrees , 15 degrees  and 20 degrees  dorsiflexion decreased
      (p<.001; p<.001 and p=.011, respectively). Tendinous reflex also significantly
      decreased. As the triceps surae parameters are diminished after the vibration
      program, it could be beneficial to immobilized persons as hypo-activity is known
      to increase muscular stiffness.

PMID- 21084201
TI  - Dysesthesia with pain due to a broken endodontic instrument lodged in the
      mandibular canal--a simple deroofing technique for its retrieval: case report.
AB  - This article presents a simple deroofing technique to retrieve a broken
      endodontic file lodged in the mandibular canal and causing dysesthesia with pain.
      Many unsuccessful attempts were made to retrieve the broken instrument. The
      deroofing technique described is simple, requiring local anesthesia and done on
      an outpatient basis with minimum morbidity. A brief review of the literature on
      dysesthesia of the inferior alveolar nerve caused by endodontic materials is also
      presented.

PMID- 21084202
TI  - Improving the accuracy of MRI spleen and liver volume measurements: a phase III
      Gaucher disease clinical trial setting as a model.
AB  - PURPOSE: To achieve minimal inter-observer variability in assessment of spleen
      and liver volume changes using a novel MRI reading method in the context of a
      phase III clinical trial of a new therapy for Gaucher disease. MATERIALS AND
      METHODS: Abdominal MRI examinations at screening and after 6 and 9 months'
      exposure to a novel plant-cell-derived recombinant enzyme, taliglucerase alfa,
      were taken in 31 patients with Gaucher disease and at least 8-fold greater than
      expected splenomegaly. Transverse T2, T1, and in/out-of-phase, and coronal T1
      sequences were performed using standardized settings across 11 sites globally.
      Spleen and liver volumes were semi-automatically delineated using an automatic
      segmentation algorithm followed by manual correction by experienced technologists
      using advanced editing tools. Data of all randomized patients were then submitted
      for efficacy evaluation to two independent experts blinded to time-point and
      treatment. RESULTS: Mean (+/- SD) percent variability over all time-points was
      0.30% +/- 0.46% for spleen and 0.53% +/- 0.69% for liver using 178 spleen and
      liver volumes measured twice. Adjudication due to >= 5% variability between
      observers was not required. CONCLUSION: The measurement method was found to be
      precise in monitoring spleen and liver volume changes over time, with a much
      lower variability than traditional manual methods, supporting the accuracy of the
      results. Given the observed minimal variability rates among multiple readers, a
      single read of each volume would be sufficient.

PMID- 21084203
TI  - Impact of imiglucerase on the serum glycosylated-ferritin level in Gaucher
      disease.
AB  - Gaucher disease (GD) is a lysosomal storage disorder, caused by deficient
      activity of the enzyme glucocerebrosidase, which can be treated by enzyme
      replacement therapy (ERT). No prognostic marker can predict long-term
      complications of GD but several markers are used in therapeutic monitoring:
      chitotriosidase, total serum ferritin (TSF), angiotensin-converting enzyme (ACE)
      and tartrate-resistant acid phosphatase (TRAP). They all increase with disease
      progression and generally decrease under ERT. This study was undertaken to
      investigate ferritin glycoforms, i.e., glycosylated ferritin (GF) and non
      glycosylated ferritin (NGF) concentrations, as potential markers for the follow
      up of GD therapy. GF and NGF determinations for GD patients followed in a single
      center between 1996 and 2007 were analyzed using two approaches: (1) the serum
      levels of 12 untreated patients were compared with those of 10 patients after 48
      months on ERT; (2) the evolution of serum levels under ERT in 15 patients were
      analyzed using linear/logarithmic mixed models. TSF and NGF levels did not
      differed significantly between untreated patients and those on ERT (TSF: 524.5
      (range 221.0-2045.0) MUg/L vs. 410.5 (range 115.0-1587.0) MUg/L, respectively,
      p=0.72; NGF: 340.0 (range 182.8-1717.8) MUg/L vs. 199.9 (range 77.1-649.8) MUg/L,
      p=0.09). The percent GF was significantly lower in untreated patients than in
      those on ERT (27.0% (range 8.0-51.0) vs. 43.5% (range 22.0-80.0) respectively;
      p=0.02). The percent GF increased significantly during ERT (slope=0.156% [95%
      confidence interval (CI), 0.03; 0.29] per month, p=0.01) regardless of whether
      NGF and TSF significantly decreased during ERT (slope=-1.4% per month [95%CI, 
      1.9%; -1.0%], p<0.0001; slope=-1.1% [95%CI, -1.6%; -0.6%] per month, p<0.0007,
      respectively). Thus, GF is low in untreated GD patients. GF and NGF changed
      significantly under ERT and might be of clinical value for GD management under
      treatment.

PMID- 21084205
TI  - Theoretical aspects of dynamic nuclear polarization in the solid state - the
      solid effect.
AB  - Dynamic nuclear polarization has gained high popularity in recent years, due to
      advances in the experimental aspects of this methodology for increasing the NMR
      and MRI signals of relevant chemical and biological compounds. The DNP mechanism
      relies on the microwave (MW) irradiation induced polarization transfer from
      unpaired electrons to the nuclei in a sample. In this publication we present
      nuclear polarization enhancements of model systems in the solid state at high
      magnetic fields. These results were obtained by numerical calculations based on
      the spin density operator formalism. Here we restrict ourselves to samples with
      low electron concentrations, where the dipolar electron-electron interactions can
      be ignored. Thus the DNP enhancement of the polarizations of the nuclei close to
      the electrons is described by the Solid Effect mechanism. Our numerical results
      demonstrate the dependence of the polarization enhancement on the MW irradiation
      power and frequency, the hyperfine and nuclear dipole-dipole spin interactions,
      and the relaxation parameters of the system. The largest spin system considered
      in this study contains one electron and eight nuclei. In particular, we discuss
      the influence of the nuclear concentration and relaxation on the polarization of
      the core nuclei, which are coupled to an electron, and are responsible for the
      transfer of polarization to the bulk nuclei in the sample via spin diffusion.

PMID- 21084204
TI  - Pore diameter mapping using double pulsed-field gradient MRI and its validation
      using a novel glass capillary array phantom.
AB  - Double pulsed-field gradient (d-PFG) MRI can provide quantitative maps of
      microstructural quantities and features within porous media and tissues. We
      propose and describe a novel MRI phantom, consisting of wafers of highly ordered
      glass capillary arrays (GCA), and its use to validate and calibrate a d-PFG MRI
      method to measure and map the local pore diameter. Specifically, we employ d-PFG
      Spin-Echo Filtered MRI in conjunction with a recently introduced theoretical
      framework, to estimate a mean pore diameter in each voxel within the imaging
      volume. This simulation scheme accounts for all diffusion and imaging gradients
      within the diffusion weighted MRI (DWI) sequence, and admits the violation of the
      short gradient pulse approximation. These diameter maps agree well with pore
      sizes measured using both optical microscopy and single PFG diffusion diffraction
      NMR spectroscopy using the same phantom. Pixel-by-pixel analysis shows that the
      local pore diameter can be mapped precisely and accurately within a specimen
      using d-PFG MRI.

PMID- 21084206
TI  - [Histologic assessment of treatment effect of preoperative chemoradiation in
      patients presenting with resectable pancreatic adenocarcinoma].
AB  - PURPOSE: Several phase II studies have shown the feasibility of neoadjuvant
      chemoradiation regimens for resectable localized pancreatic adenocarcinoma.
      However, there is to date no completed phase III study to validate this approach
      and treatment effects evaluation still remains an active area of investigation.
      From the mature results of the SFRO-FFCD 9704 trial, we explored the antitumoral
      effect of a 5-fluoro-uracil and cisplatin-based preoperative chemoradiation
      regimen, with a special highlight on the histopathological response and performed
      a literature review. PATIENTS AND METHODS: Treatment consisted of concurrent
      radiotherapy (50 Gy within five weeks) and chemotherapy with 5-fluoro-uracil (300
      mg/m(2)/day, five days/week, weeks 1-5) and cisplatin (20mg/m(2)/day, days 1-5
      and 29-33), followed by surgical resection of the pancreatic tumour in patients
      without progression. RESULTS: In all, 41 patients were enrolled, 26 patients
      (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0
      resection. A total of 13 of 26 specimens (50%) presented a major pathologic
      response (>= 80% of severely degenerative cancer cells), with one complete
      pathologic response. The local recurrence and two-year survival rates were 4 and
      32%, respectively, for the 26 operated patients. CONCLUSION: Our results suggest
      that preoperative chemoradiation provides antitumoral effect associated with
      major histopathological response in 50% of patients and a high R0 resection rate.
      Evaluation of histopathological response to neoadjuvant chemoradiation may serve
      as a surrogate marker for treatment efficacy and further research is needed to
      determine new prognostic and predictive factors of treatment response.

PMID- 21084208
TI  - [Induced membrane technique for bone defects in the hand and wrist].
AB  - The induced membrane technique of bone reconstruction initially proposed for long
      bone defects can be extended to the hand and wrist defects. The two stages
      procedure is particularly useful in infected lesions or when the viability of the
      segment is not initially acquired. It avoids to have recurs to vascularised bone
      transfers which are not reliable in septic conditions and not easily performed in
      emergency. The induced membrane technique offers great capacities of bone
      reconstruction whatever the sizes of the defect.

PMID- 21084207
TI  - [Early stage breast cancer: is exclusive radiotherapy an option for early breast
      cancers with complete clinical response after neoadjuvant chemotherapy?].
AB  - PURPOSE: To determine whether exclusive radiotherapy could be a therapeutic
      option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT)
      for early breast cancers (EBC). PATIENTS AND METHODS: Between 1985 and 1999, 1477
      patients received neoadjuvante chemotherapy for early breast cancer considered to
      be too large for primary conservative surgery. Of 165 patients with complete
      clinical response, 65 were treated by breast surgery (with radiotherapy) and 100
      by exclusive radiotherapy. RESULTS: The two groups were comparable in terms of
      baseline characteristics, except for larger initial tumor sizes in the exclusive
      radiotherapy group. There were no significant differences in overall, disease
      free and metastasis-free survivals. Five-year and 10-year overall survivals were
      91 and 77% in the no surgery group and 82 and 79% in the surgery group,
      respectively (P = 0.9). However, a non-significant trend towards higher
      locoregional recurrence rates (LRR) was observed in the no surgery group (31 vs.
      17% at 10 years; P = 0.06). In patients with complete responses on mammography
      and/or ultrasound, LRR were not significantly different (P=0.45, 10-year LRR: 21
      in surgery vs. 26% in exclusive radiotherapy). No significant differences were
      observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities.
      CONCLUSION: Surgery is a key component of locoregional treatment for breast
      cancers that achieved complete clinical response to neoadjuvant chemotherapy.

PMID- 21084209
TI  - [Osteoarthritis of the trapeziometacarpal joint in men: different stakes. Results
      of three surgical techniques].
AB  - Basal thumb arthritis is less common in men, but the functional implication is
      different in this manual worker or active retired population. The objective was
      to analyse the results of three surgical procedure in an exclusively men's
      population. Twenty-eight patients (19 partial trapeziectomy with interposition of
      a chondrocostal autograft, seven total trapeziectomy and two prosthesis), with a
      mean age of 69 years old, were reviewed at a mean follow-up of 71 months.
      Mobility and pain were similar in the three populations. But the strength and
      Dash scores were better in the cartilage group. Radiologically the length of the
      thumb ray was greater in the cartilage group and no signs of loosening were
      observed in the prosthesis group. The surgery of reference in this population is
      the arthrodesis of the trapeziometacarpal joint. But the lack of mobility is
      disabling, the strength is questionable and painlessness varies due to high rates
      of non-union. Only one study compared four surgical procedures in an exclusively
      male population and total trapeziectomy seemed to give the best results. But this
      technique carries risk of shortening of the thumb ray. Even if the comparison is
      difficult, the association of partial trapeziectomy with interposition of costal
      cartilage graft seems to give better stability to the thumb column by preserving
      length as well as greater strength compared to total trapeziectomy. We advocate
      this procedure for basal thumb arthritis in men.

PMID- 21084210
TI  - [Vascularized iliac crest and distal radius reconstruction].
AB  - The authors relate their experience concerning the vascularized iliac crest flap.
      In the first chapter, they detail the anatomic vascularized osteocutaneous iliac
      crest. Blood supply arises from the deep and superficial circonflexe iliac
      artery. Many anastomoses connect the two systems. In the second chapter, they
      detail the operative technique of free and pedicule hone iliac crest flap.
      Composite cutaneous bone flaps are also detailed. In the third chapter, they
      detail informations about treatment of distal radius bone defects with associated
      skeen flap if necessary.

PMID- 21084212
TI  - Oseltamivir-induced dyskinesia in Parkinson's disease.

PMID- 21084211
TI  - Diagnostic accuracy and agreement across three depression assessment measures for
      Parkinson's disease.
AB  - PURPOSE: To assess diagnostic accuracy of two self-administered depression
      measures compared to an interviewer-administered measure in subjects with
      Parkinson's disease (PD), and to analyze clinical and sociodemographic factors
      associated with disagreement among the three depression assessment tools.
      METHODS: We assessed 214 PD subjects using the Patient Health Questionnaire-9
      (PHQ-9), the Geriatric Depression Scale-15 (GDS-15), and the Structured Clinical
      Interview for the DSM-IV depression module (SCID). Diagnostic accuracy of the PHQ
      9 and GDS-15 compared to the SCID was evaluated. Multivariate logistic regression
      was conducted to analyze factors associated with measure disagreement. We
      compared item agreement between the PHQ-9 and SCID to test the hypothesis that
      there would be less agreement between items assessing depression symptoms
      overlapping with common PD symptoms, compared to items having minimal overlap
      with PD manifestations. RESULTS: Compared to SCID diagnosis of major depression,
      PHQ-9 sensitivity is 50% and specificity is 93%; GDS-15 sensitivity is 43% and
      specificity is 96%. The GDS-15 has 85% sensitivity and 79% specificity and the
      PHQ-9 has 54% sensitivity and 85% specificity compared to SCID diagnosis of minor
      or major depression. The PHQ-9 and SCID show more agreement on items unrelated to
      PD manifestations. Pain was the only factor associated with disagreement between
      the SCID and PHQ-9. CONCLUSION: Compared to the PHQ-9, the GDS-15 had higher
      sensitivity and similar positive predictive value, suggesting it is a superior
      screening tool in clinical applications for PD. On future depression screening or
      diagnostic instruments, consideration should be given to excluding depression
      items overlapping with PD manifestations.

PMID- 21084213
TI  - Tolerability and efficacy of switching from oral selegiline to Zydis selegiline
      in patients with Parkinson's disease.
AB  - Selegiline is a monoamine-B specific inhibitor used to treat Parkinson's disease.
      A Zydis sublingual preparation has more efficient absorption and less first pass
      amphetamine metabolites. We conducted an open label oral to Zydis switch study to
      evaluate tolerability of rapid switch, and relative efficacy, in 48 subjects from
      5 sites. Overall patients preferred the Zydis preparation. Per clinician global
      impressions, fluctuations improved and the "on" UPDRS part II scores improved.
      Total UPDRS and measures of fatigue and sleep were unchanged. Adverse events were
      mild. Patients generally preferred the Zydis selegiline preparation but the
      modest difference is of unclear clinical significance given the open label nature
      of the trial.

PMID- 21084215
TI  - IL-17 in obesity and adipogenesis.
AB  - The pro-inflammatory cytokine interleukin (IL)-17 (also known as IL-17) has been
      associated with induction of tissue inflammation. Obese individuals exhibit many
      symptoms of chronic low-grade inflammation, suggesting that IL-17 may impact
      adipose tissue. However, the role of IL-17 in obesity is largely unexplored.
      Emerging studies indicate that obesity selectively promotes expansion of the Th17
      T-cell lineage, exacerbating disease in murine models of autoimmunity such as EAE
      and colitis. Human studies support this concept, as new clinical studies suggest
      that IL-17 is expressed at elevated levels in obese individuals. Conversely,
      however, an anti-adipogenic role for IL-17 is becoming evident, and therefore the
      interconnections between IL-17 and fat metabolism may be quite complex. Here, we
      consolidate the potential implications of IL-17 in relation to obesity and
      describe the emerging data regarding the role of IL-17 in adipose tissue.

PMID- 21084217
TI  - Unilateral superior pellucid marginal degeneration in a case with ichthyosis.
AB  - A 47-year-old man with ichthyosis vulgaris presented to our hospital complaining
      of reduced visual acuity and ocular discomfort in the left eye. Slit-lamp
      biomicroscopy revealed a thinning about 2mm from the superior limbus and
      superficial punctate corneal lesions in the left eyes. Corneal topography was
      'butterfly-like' in an area of increased elevation in the left eye. Although
      ichthyosis vulgaris and unilateral superior pellucid marginal degeneration are
      both uncommon conditions, this is first report about these two conditions in
      studied together.

PMID- 21084216
TI  - Semi-automatic segmentation for prostate interventions.
AB  - In this paper we report and characterize a semi-automatic prostate segmentation
      method for prostate brachytherapy. Based on anatomical evidence and requirements
      of the treatment procedure, a warped and tapered ellipsoid was found suitable as
      the a-priori 3D shape of the prostate. By transforming the acquired endorectal
      transverse images of the prostate into ellipses, the shape fitting problem was
      cast into a convex problem which can be solved efficiently. The average whole
      gland error between non-overlapping volumes created from manual and semi
      automatic contours from 21 patients was 6.63 +/- 0.9%. For use in brachytherapy
      treatment planning, the resulting contours were modified, if deemed necessary, by
      radiation oncologists prior to treatment. The average whole gland volume error
      between the volumes computed from semi-automatic contours and those computed from
      modified contours, from 40 patients, was 5.82 +/- 4.15%. The amount of bias in
      the physicians' delineations when given an initial semi-automatic contour was
      measured by comparing the volume error between 10 prostate volumes computed from
      manual contours with those of modified contours. This error was found to be 7.25
      +/- 0.39% for the whole gland. Automatic contouring reduced subjectivity, as
      evidenced by a decrease in segmentation inter- and intra-observer variability
      from 4.65% and 5.95% for manual segmentation to 3.04% and 3.48% for semi
      automatic segmentation, respectively. We characterized the performance of the
      method relative to the reference obtained from manual segmentation by using a
      novel approach that divides the prostate region into nine sectors. We analyzed
      each sector independently as the requirements for segmentation accuracy depend on
      which region of the prostate is considered. The measured segmentation time is 14
      +/- 1s with an additional 32 +/- 14s for initialization. By assuming 1-3 min for
      modification of the contours, if necessary, a total segmentation time of less
      than 4 min is required, with no additional time required prior to treatment
      planning. This compares favorably to the 5-15 min manual segmentation time
      required for experienced individuals. The method is currently used at the British
      Columbia Cancer Agency (BCCA) Vancouver Cancer Centre as part of the standard
      treatment routine in low dose rate prostate brachytherapy and is found to be a
      fast, consistent and accurate tool for the delineation of the prostate gland in
      ultrasound images.

PMID- 21084218
TI  - Effect of gold nanoparticles on the fluorescence excitation spectrum of alpha
      fetoprotein: local environment dependent fluorescence quenching.
AB  - The effect of colloid gold nanoparticles (AuNPs) on the fluorescence excitation
      spectrum of alpha-fetoprotein (AFP) has been investigated experimentally. The
      excitation spectral peaks of AFP with low concentration from 0.01 ng ml(-1) to 12
      ng ml(-1) increase monotonically with increasing of AFP concentration. When some
      gold colloids were added to the AFP solution, the excitation peak at 285 nm
      decreases distinctly. By comparing the excitation peak intensity of AFP solution
      with gold colloids and without gold colloids at different AFP concentrations, the
      quenching effect from gold nanoparticle was more effective at lower AFP
      concentration. So the range of concentration from 0.01 ng ml(-1) to 0.09 ng ml(
      1) will be the potential range of applications because of the higher sensitivity.
      The physical origin based on local field effect was investigated to illuminate
      this local environment dependent fluorescence quenching. The changing extent of
      quenching with different AFP concentrations can be attributed to the nonlinear
      decreasing of the local field factor of gold nanoparticles as a function of
      environmental dielectric constant.

PMID- 21084220
TI  - First report of an autochthonous hepatitis E virus genotype 3 infection in a 5
      month old female child in Germany.
AB  - Hepatitis E virus (HEV) is well-known to cause endemic outbreaks of hepatitis in
      tropical countries, mostly caused by HEV genotypes 1 or 2 and transmitted from
      humans to humans via the fecal-oral route. In contrast, HEV genotypes 3 or 4 are
      commonly encountered as sporadic cases in a non-endemic setting; these
      autochthonous cases are transmitted from animals to humans and commonly affect
      elderly male subjects. We report a five-month-old caucasian girl presenting with
      diarrhea, emesis, and elevated ALT. Surprisingly, acute infection with Hepatitis
      E virus (HEV) genotype 3 was laboratory-confirmed by reverse transcriptase
      polymerase chain reaction (RT-PCR) and sequencing. Thirteen months later, RT-PCR
      for HEV from stool tested negative whereas anti-HEV IgG in serum tested positive.
      Neither HEV RNA nor anti-HEV antibodies could be detected in stool or serum of
      the parents. To our knowledge, this is the first pediatric case of a HEV
      infection in Germany. Thus, HEV should be included into the differential
      diagnosis of pediatric infectious liver and bowel disease.

PMID- 21084219
TI  - Fluorimetric assay of interaction of protein with ferrofluids.
AB  - Magnetic iron oxide nanoparticles are inherently biocompatible and are amenable
      to post synthesis surface modification, making them excellent candidates for many
      important applications. If the above can be achieved in a single-step i.e., in
      situ synthesis and functionalization, the results are expected to be more
      dramatic for sensitive detection of biomolecules. For any application, it is
      necessary to confer a high level of binding specificity through surface
      chemistry, which can be introduced by using biological moieties that possess lock
      and-key interactions, like those observed in antibody-antigen and enzyme
      substrate recognition. In this paper, we have synthesized water based ferrofluids
      with serum albumin, the major protein component of blood. A series of other
      ferrofluids using different biocompatible polymers have also been studied with
      respect to their size determined by transmission electron microscopy, magnetic
      behavior with the aid of vibrating sample magnetometry and binding capability to
      bovine serum albumin by quenching of its native fluorescence. From our results,
      it can be inferred that binding has taken place between magnetic particles and
      biomolecules, the binding constants of which indirectly reveal the efficiency of
      the interaction.

PMID- 21084214
TI  - Signal transduction pathways and transcriptional regulation in Th17 cell
      differentiation.
AB  - Over the last decade, our understanding of helper/effector T cell differentiation
      has changed dramatically. The discovery of interleukin (IL-)17-producing T cells
      (Th17) and other subsets has changed our view of T cell-mediated immunity.
      Characterization of the signaling pathways involved in the Th17 commitment has
      provided exciting new insights into the differentiation of CD4+ T cells.
      Importantly, the emerging data on conversion among polarized T helper cells have
      raised the question how we should view such concepts as T cell lineage
      commitment, terminal differentiation and plasticity. In this review, we will
      discuss the current understanding of the signaling pathways, molecular
      interactions, and transcriptional and epigenetic events that contribute to Th17
      differentiation and acquisition of effector functions.

PMID- 21084221
TI  - High-rate nitrogen removal from anaerobic digester liquor using an up-flow
      anammox reactor with polyethylene sponge as a biomass carrier.
AB  - Here, the stable performance of nitrogen removal from digester liquor after
      partial nitrification was experimentally demonstrated in an up-flow anammox
      reactor with polyethylene sponge (PE sponge) as a biomass carrier. A high
      nitrogen loading rate of 8.4 kg-N/m(3)/day with a TN removal rate of 7.6 kg
      N/m(3)/day was obtained in this study, indicating PE sponge carrier is effective
      to attain high nitrogen removal performance. This high NLR should be mainly
      attributed to the successfully operational strategy, the biomass carrier with
      strong adsorption as well as the functional microbial community. The reaction
      ratio of NH(4)(+):NO(2)(-):NO(3)(-) using the anaerobic digester liquor as
      feeding media was 1:1.09:0.14. In addition, the channeling phenomenon was
      investigated in this study, and the problem could be solved through keeping the
      sludge bed lower than 2/3 of the effective height of the reactor. Furthermore,
      the settling property of the anammox granules was enhanced significantly and the
      bacteria community was verified by DNA analysis. The new species of anammox
      bacteria (kumadai-1) and KSU-1 were confirmed to be the predominant species after
      stable anammox performance was obtained.

PMID- 21084222
TI  - Rice sodium-insensitive potassium transporter, OsHAK5, confers increased salt
      tolerance in tobacco BY2 cells.
AB  - Potassium ion (K(+)) plays vital roles in many aspects of cellular homeostasis
      including competing with sodium ion (Na(+)) during potassium starvation and salt
      stress. Therefore, one way to engineer plant cells with improved salt tolerance
      is to enhance K(+) uptake activity of the cells, while keeping Na(+) out during
      salt stress. Here, in search for Na(+)-insensitive K(+) transporter for this
      purpose, bacterial expression system was used to characterize two K(+)
      transporters, OsHAK2 and OsHAK5, isolated from rice (Oryza sativa cv.
      Nipponbare). The two OsHAK transporters are members of a KT/HAK/KUP transporter
      family, which is one of the major K(+) transporter families in bacteria, fungi
      and plants. When expressed in an Escherichia coli K(+) transport mutant strain
      LB2003, both OsHAK transporters rescued the growth defect in K(+)-limiting
      conditions by significantly increasing the K(+) content of the cells. Under the
      condition with a large amount of extracellular Na(+), we found that OsHAK5
      functions as a Na(+)-insensitive K(+) transporter, while OsHAK2 is sensitive to
      extracellular Na(+) and exhibits higher Na(+) over K(+) transport activities.
      Moreover, constitutive expression of OsHAK5 in cultured-tobacco BY2 (Nicotiana
      tabacum cv. Bright Yellow 2) cells enhanced the accumulation of K(+) but not
      Na(+) in the cells during salt stress and conferred increased salt tolerance to
      the cells. Transient expression experiment indicated that OsHAK5 is localized to
      the plant plasma membrane. These results suggest that the plasma-membrane
      localized Na(+) insensitive K(+) transporters, similar to OsHAK5 identified here,
      could be used as a tool to enhance salt tolerance in plant cells.

PMID- 21084223
TI  - Sleep epidemiology 30 years later: where are we?

PMID- 21084224
TI  - Cost-effectiveness study comparing pharmaceutically licensed plasma for
      transfusion (OctaplasLG(r)) versus fresh frozen plasma (FFP) in critically Ill
      patients in the UK.
AB  - This study evaluates the cost-effectiveness of OctaplasLG(r) (pharmaceutically
      licensed plasma for transfusion) versus fresh frozen plasma (FFP) in critically
      ill patients in the UK using a decision-analytic approach. Transfusion with
      OctaplasLG(r) resulted in 0.03 quality adjusted life years (QALYs) and 0.03 life
      years saved compared with FFP. The discounted cost per life year was L949
      ($1504), and the discounted cost per QALY saved was L1030 ($1632) with
      OctaplasLG(r) in the UK. Based on a higher price of L70 ($111) for OctaplasLG(r)
      versus L28.42 ($45.04) for FFP, OctaplasLG(r) is considered to be cost-effective
      at a threshold of L30,000 ($47,548) per QALY.

PMID- 21084225
TI  - Transvesicoscopic cross-trigonal ureteroneocystostomy in children: a single
      center experience.
AB  - PURPOSE: To evaluate the safety and efficacy of transvesicoscopic ureteric
      reimplantation in children. PATIENTS AND METHODS: Seventeen ureteric units in 11
      patients underwent a transvesicoscopic 'Cohen' ureteroneocystostomy in 2003-2007
      and the results were retrospectively analyzed. There were four boys and seven
      girls. All patients had vesicoureteric reflux (VUR), except for one with
      paraostial diverticula. Six patients underwent bilateral and five unilateral
      transvesicoscopic reimplantation (a total of 17 units). RESULTS: The procedure
      was successfully completed in all patients. Mean operation time was 217 min in
      unilateral cases and 306 min in bilateral cases without perioperative
      complications, except for pneumoperitoneum development in two cases. In the early
      postoperative period, two patients developed macroscopic hematuria. Mean hospital
      stay was 3.8 days (3-5 days), except for one patient who suffered from urinary
      tract infection and needed longer hospitalization. Mean follow-up period was 4.5
      years (3-7 years). One patient with bilateral VUR had passive unilateral grade I
      VUR on postoperative cystogram, giving a success rate of 91% (94% of ureters).
      This patient was followed conservatively. One patient had recurrent urinary tract
      infections without reflux. CONCLUSION: Transvesicoscopic cross-trigonal
      ureteroneocystostomy can be safely performed with a high success rate in
      children.

PMID- 21084226
TI  - Fear as the only clinical expression of affective focal status epilepticus.
AB  - Affective seizures consist of fear, depression, joy, and (rarely) anger. A
      correct diagnosis is often delayed as the behavioral features, like fear, are
      interpreted as psychiatric disorders. We describe a patient with affective focal
      status epilepticus (AFSE) in which fear was the only clinical manifestation. We
      present electroencephalographic correlates and discuss the diagnostic
      difficulties that can be encountered in similar cases. AFSE with fear as the only
      clinical expression may represent a diagnostic challenge. When fear is the only
      or the prominent behavioral feature, seizures may be diagnosed as panic attacks,
      leading to erroneous therapy. In such situations, electroencephalography is an
      essential tool in differentiating between psychiatric disorders and epileptic
      events.

PMID- 21084227
TI  - Optimization of a ligand immobilization and azide group endcapping concept via
      "Click-Chemistry" for the preparation of adsorbents for antibody purification.
AB  - This report describes and compares different strategies to deactivate (endcap)
      epoxide groups and azide groups on bio-chromatographic support surfaces, before
      and after ligand attachment. Adsorbents possessing epoxide groups were
      deactivated using acidic hydrolysis or were endcapped with 2-mercaptoethanol or 2
      ethanolamine. The influence of surface-bound 2-ethanolamine was demonstrated for
      the triazine-type affinity adsorbent B14-2LP-FractoAIMs-1, which was tested in
      combination with the weak anion exchange material 3-aminoquinuclidine-FractoAIMs
      3 (AQ-FA3). Azide groups were modified with 2-propargylalcohol using Click
      Chemistry. Besides the conventional one-pot Click reaction, an alternative
      approach was introduced. This optimized Click protocol was employed (i) for the
      preparation of the weak anion exchange material AdQ-triazole-Fractogel (AdQ-TRZ
      FG) and (ii) for the endcapping of residual azide groups with 3-propargyl
      alcohol. Using the new Click reaction protocol the ligand immobilization rate was
      doubled from 250 to 500 MUmol/g dry adsorbent. Furthermore, the modified support
      surface was proven to be inert towards the binding of immunoglobulin G (IgG) as
      well as feed impurities. A thorough evaluation of modified surfaces and
      adsorbents was performed with dynamic binding experiments using cell culture
      supernatant containing monoclonal human immunoglobulin G (h-IgG-1). Besides SDS
      Page, a recently introduced Protein A-size exclusion HPLC method (PSEC-HPLC) was
      used to visualize the feed impurity composition and the IgG content of all
      collected sample fractions in simple PSEC-Plots. A surprising outcome of this
      study was the irreversible binding of IgG to azide modified surfaces. It was
      found that organic azide compounds, e.g. 1-azide-3-(2-propen-1-yloxy)-2-propanol
      (AGE-N3) promote antibody aggregation to a slightly higher extent than the
      inorganic sodium azide. The possibility that the Hofmeister Series of salt anions
      may be applicable to predict the properties of the corresponding organic
      compounds is discussed.

PMID- 21084228
TI  - Does embodiment need to be pushed even further? Comment on "Embodied language,
      best fit analysis, and formal compositionality" by J. Feldman.

PMID- 21084231
TI  - Defrauding of the global fund gives Sweden cold feet.

PMID- 21084232
TI  - US foreign aid restructuring: is it "a very big deal"?

PMID- 21084233
TI  - India is failing the mentally ill as abuses continue.

PMID- 21084236
TI  - Technophilia and the pharmaceutical fix.

PMID- 21084239
TI  - Heat waves in the United States: mortality risk during heat waves and effect
      modification by heat wave characteristics in 43 U.S. communities.
AB  - BACKGROUND: Devastating health effects from recent heat waves, and projected
      increases in frequency, duration, and severity of heat waves from climate change,
      highlight the importance of understanding health consequences of heat waves.
      OBJECTIVES: We analyzed mortality risk for heat waves in 43 U.S. cities (1987
      2005) and investigated how effects relate to heat waves' intensity, duration, or
      timing in season. METHODS: Heat waves were defined as >= 2 days with temperature
      >= 95th percentile for the community for 1 May through 30 September. Heat waves
      were characterized by their intensity, duration, and timing in season. Within
      each community, we estimated mortality risk during each heat wave compared with
      non-heat wave days, controlling for potential confounders. We combined individual
      heat wave effect estimates using Bayesian hierarchical modeling to generate
      overall effects at the community, regional, and national levels. We estimated how
      heat wave mortality effects were modified by heat wave characteristics
      (intensity, duration, timing in season). RESULTS: Nationally, mortality increased
      3.74% [95% posterior interval (PI), 2.29-5.22%] during heat waves compared with
      non-heat wave days. Heat wave mortality risk increased 2.49% for every 1 degrees
      F increase in heat wave intensity and 0.38% for every 1-day increase in heat wave
      duration. Mortality increased 5.04% (95% PI, 3.06-7.06%) during the first heat
      wave of the summer versus 2.65% (95% PI, 1.14-4.18%) during later heat waves,
      compared with non-heat wave days. Heat wave mortality impacts and effect
      modification by heat wave characteristics were more pronounced in the Northeast
      and Midwest compared with the South. CONCLUSIONS: We found higher mortality risk
      from heat waves that were more intense or longer, or those occurring earlier in
      summer. These findings have implications for decision makers and researchers
      estimating health effects from climate change.

PMID- 21084240
TI  - [Genetic instability as a driver for oncogenesis].
AB  - Genomic DNA displays a non canonical structure prone to be damaged and modified
      by genotoxic stresses, which are induced either by the endogenous metabolism or
      attacks from environment or therapeutic pressure. Several molecular pathways
      allow cells to repair such DNA lesions. Additional mechanisms have been selected
      to bypass such damage at the price of mutations. The maintenance of the genome is
      thus mediated by the respect of a balance between accurate and inaccurate DNA
      transactions. This review deals with the tumor suppressor role of such
      equilibrium, as well as the impact of an unbalance on carcinogenesis.

PMID- 21084241
TI  - [Epithelial mesenchymal transition during development in fibrosis and in the
      progression of carcinoma].
AB  - Epithelial mesenchymal transition (EMT) is a fundamental mechanism controlling
      multiple events during embryonic development. Mesenchymal cells appear
      transiently in some diploblasts, the most primitive species characterized by two
      epithelial layers. Since almost 800 million years, EMT has been conserved
      throughout evolution to control morphogenetic events, such as the formation of
      the three primary germ layers during gastrulation. Most interestingly, specific
      molecular pathways have been conserved in many different species to drive EMT. In
      the animal kingdom, a recurrent theme is that EMT controls the intercellular
      adhesion machinery and the dynamics of its associated cytoskeleton. EMT pathways
      are also tightly connected to determination and differentiation programs, and are
      reactivated in adult tissues following injury or exposure to toxic agents. EMT is
      now shown to operate during the early stages of carcinoma invasion leading to
      blood or lymph vessel intravasation of malignant cells. The converse mechanism -
      mesenchymal-epithelial transition (MET) - then operates at distant sites from the
      primary tumor to form macrometastases from isolated micrometastatic cells. The
      mesenchymal-like state of carcinoma confers stemness, protection from cell death,
      escape from immune response and, most importantly, resistance to conventional and
      targeted therapies. Our laboratory has designed an EMT high-throughput screen of
      small molecular weight compounds and biologics in order to establish new
      therapeutic approaches that interfere with the plasticity of carcinoma cells. New
      therapeutic interventions are envisioned to delay tumor recurrence.

PMID- 21084242
TI  - [Molecular biology of soft-tissue sarcomas].
AB  - Sarcomas represent a heterogeneous group of tumors with a complex and poorly
      reproducible classification. However, in the last ten years, several specific
      genetic alterations have been described allowing a molecular classification with:
      1) sarcomas with a specific translocation which can be used as a diagnostic
      marker. These translocations can be demonstrated by RT-PCR or by FISH with
      commercially available break apart probes ; 2) sarcomas with simple genomic
      profile showing amplification of a few genes. Well differentiated liposarcomas,
      dedifferentiated liposarcomas and intimal sarcomas show a simple genomic profile
      characterised by MDM2 and CDK4 amplifications associated with amplification of
      other genes in dedifferentiated liposarcomas ; 3) sarcomas with activating
      mutations: about 90% of GIST show activating mutation of a receptor tyrosine
      kinase gene, either KIT or PDGFRA. The most frequent mutation involves exon 11 of
      KIT followed by exon 9 of KIT and exon 18 of PDGFRA. Demonstration of these
      mutations is useful for the diagnosis of CD117 negative GIST, for predicting
      response to imatinib and to explain secondary resistance to imatinib ; 4)
      sarcomas with inactivating mutations: malignant rhabdoid tumors show biallelic
      inactivation of INI1 gene with a lost of INI1 expression which can be
      demonstrated by immunohistochemistry ; 5) other sarcomas usually show a complex
      genomic profile characterised by numerous gains and losses of genes with a
      frequent loss of RB1 and alterations of P53. Leiomyosarcomas, pleomorphic
      rhabdomyosarcomas, pleomorphic liposarcomas, myxofibrosarcomas, poorly
      differentiated sarcomas (so-called MFH and fibrosarcomas) belong to this category
      and show no specific molecular abnormality.

PMID- 21084243
TI  - [Molecular abnormalities in lymphomas].
AB  - Numerous molecular abnormalities have been described in lymphomas. They are of
      diagnostic and prognostic value and are taken into account for the WHO
      classification of these tumors. They also shed some light on the underlying
      molecular mechanisms involved in lymphomas. Overall, four types of molecular
      abnormalities are involved: mutations, translocations, amplifications and
      deletions of tumor suppressor genes. Several techniques are available to detect
      these molecular anomalies: conventional cytogenetic analysis, multicolor FISH,
      CGH array or gene expression profiling using DNA microarrays. In some lymphomas,
      genetic abnormalities are responsible for the expression of an abnormal protein
      (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry.
      In the present review, molecular abnormalities observed in the most frequent B, T
      or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell
      lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene
      expression signature corresponding to germinal center B-cell-like (GCB: CD10+,
      BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an
      activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among
      other B-cell lymphomas with well characterized molecular abnormalies are
      follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated
      Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma
      translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1
      transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression)
      and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma
      kinase)-positive anaplastic large cell lymphoma, well characterized molecular
      anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell
      lymphomas not otherwise specified are a heterogeneous group of tumors with
      frequent but not recurrent molecular abnormalities. Gene profiling analysis shows
      that the expression of several genes is deregulated including PDGFRA (platelet
      derived growth factor receptor) gene, encoding a receptor with tyrosine kinase
      activity. In angio-immunoblastic T-cell lymphomas molecular abnormalities are
      found in follicular helper T-cell (TFH) that express some distinctive markers
      such as CD10, PD-1, CXCR5 and the CXCL13 chemokine. ALK-positive anaplastic large
      cell lymphoma is a paradigme of T-cell lymphoma since it is associated with an X
      ALK oncogenic fusion protein due to a translocation involving ALK gene at 2p23.
      ALK tyrosine kinase activates downstream pathways (Stat3/5b, Src kinases,
      PLCgamma, PI3 kinase) implicated in lymphomagenesis, proliferation and protection
      against apoptosis. Specific ALK inhibitors are currently in clinical evaluation.
      Lastly several lymphomas are associated with infectious agents that play a direct
      (EB virus, HTLV1) or indirect role (e.g. Helicobacter pylori in MALT lymphoma) in
      lymphomagenesis.

PMID- 21084244
TI  - [Genetic and molecular abnormalities of glioblastomas (GBM)].
AB  - This presentation reports a series of data dealing with recurrent genetic
      abnormalities and gene expression profiles that characterize primary
      glioblastomas and secondary glioblastomas resulting from the transformation of
      low grade tumors (grade II and III astrocytomas and oligodendrogliomas). The most
      recent aspects of the concept of tumor stem cells that may explain the relentless
      growth of GBM will be reported. Molecular features of tumor neoangiogenesis will
      be described. Epigenetic alterations and deregulation of gene expression by
      microRNAs (miRs) will be also included. Some aspects of tumor predisposition will
      be also discussed. Finally, a short description of exosomes as vectors of tumor
      information will be presented.

PMID- 21084245
TI  - Treatment failure with antagonists of TNF-alpha: mechanisms and implications for
      the care of patients.
AB  - The use of TNF-alpha antagonists has substantially improved the care of many
      patients with inflammatory and autoimmune diseases. However, approximately one
      third of such patients fail to respond well to treatment, regardless of the
      antagonist used or of the underlying disease. The mechanisms underlying these
      failures are analyzed in this review, and proposals made concerning how best to
      adapt therapeutic decisions in these instances.

PMID- 21084246
TI  - Effect of omeprazole on the concentration of interleukin-6 and transforming
      growth factor-beta1 in patients receiving dual antiplatelet therapy after
      percutaneous coronary intervention.
AB  - BACKGROUND: Dual antiplatelet therapy (aspirin plus clopidogrel) is recommended
      in patients undergoing percutaneous coronary intervention (PCI). Treatment with
      proton pump inhibitors (PPIs) decreases bleeding rate. Alarming reports have been
      made that PPIs may decrease the antiplatelet activity of clopidogrel. We sought
      to determine whether levels of interleukin-6 (IL-6) and transforming growth
      factor-beta1 (TGF-beta1) might help distinguish individuals at risk for adverse
      events. METHODS: Thirty-eight patients on aspirin and clopidogrel were enrolled
      and divided into two groups: group 1 [patients receiving omeprazole (n = 18)] and
      group 2 [patients not receiving omeprazole (n = 20)]. Patients underwent PCI and
      were scheduled for twelve-month clinical follow-up. The major, adverse cardiac
      and cerebrovascular events (MACCE) include death, re-hospitalization for acute
      coronary syndromes, and stroke. RESULTS: Median concentrations of IL-6 were
      higher in group 1 at 4.7 pg/mL, in comparison with group 2, 1.65 pg/mL (p =
      0.003). Median concentrations of TGF-beta1 were similar in both groups (p = 0.5).
      Patients in group 1 had a significantly higher leukocyte count [103/mm3] (median
      7.5 vs 6.5; p = 0.04). There were no deaths during follow-up. The incidence of
      myocardial infarction was higher in group 1 (33.4% vs 5.0%; p = 0.03). MACCE at
      twelve months were more frequent in group 1 (55.6% vs 20.0%; p = 0.02). The cut
      off value to predict MACCEs for IL-6 was > 3.6 pg/mL (sensitivity 64%,
      specificity 88%, positive predictive value 75%, negative predictive value 81%).
      INTERPRETATION: We show here that concomitant omeprazole use is associated with
      an increased inflammatory reaction. Drug interactions may reduce the anti
      inflammatory effect of clopidogrel. This mechanism maybe responsible for an
      increased risk of non-fatal, cardiovascular events, following stent placement.

PMID- 21084247
TI  - Statistical analysis of transcallosal propagation of spikes arising from the
      mesial frontal area.
AB  - OBJECTIVE: To study the connections between bilateral mesial frontal (MF)
      regions. METHODS: We evaluated synchrony of spikes, recorded by subdural
      electrodes, arising from bilateral MF regions using cross correlation in MF
      epilepsy. A seven-year-old boy with intractable daily bilateral asymmetric tonic
      seizures and a normal MRI was investigated. To confirm the lateralization of
      epileptogenicity, subdural electrodes were implanted bilaterally. Only spikes of
      an amplitude of 400 MUV or more were analyzed. RESULTS: Of 92.4% (194/210) of the
      left MF spikes recorded for 30 minutes, an approximately synchronous spike was
      also detected in the right MF region. Cross correlation analysis demonstrated
      that for 88.7% of the bilateral MF spikes (172/194, 88.7%) the left MF spike led
      the contralateral spikes with relative fixed peak-to-peak intervals (18.9 +/-
      11.1 ms) and high cross correlation values (0.81 +/- 0.10). An estimated
      conduction velocity of 7.2 +/- 9.8 m/sec was calculated (assuming no synaptic
      delay). After a second period of more extended invasive EEG monitoring, a left
      partial frontal lobectomy was performed and the patient immediately had a few
      brief seizures before remaining seizure-free for a follow-up period of 14 months.
      CONCLUSION: We conclude that the propagation of spikes between bilateral MF
      regions most likely occurs mainly through myelinated callosal fibres. In
      addition, this cross correlation method showed that the left MF spikes, most of
      the time, preceded the right MF spikes suggesting that the epileptogenic zone was
      localized in the left MF region.

PMID- 21084248
TI  - [Food supplements on the domestic market in Hungary: nutritional assessment of
      the ingredients, risks and benefits, the role of food supplements in human
      nutrition].
AB  - Food supplements are foods that are concentrated sources of nutrients such as
      vitamins and minerals and other substances with a physiological or nutritional
      effect. Since joining to the European Union, the distribution of food supplements
      in Hungary has not been bound to pre-market authorisation; products can be placed
      to the market after a formal notification at the National Institute for Food and
      Nutrition Science. Distribution, ingredients, and all information on the label
      are determined by numerous regulations but at the same time, the lack of
      harmonized legislation at Community level may cause a lot of problems. In the
      second part of the review authors introduce the evaluation process of components
      from the point of view of nutritional and physiological effects and the possible
      role of food supplements in human nutrition.

PMID- 21084249
TI  - [General anesthesia during double balloon enteroscopy--Hungarian experiences].
AB  - Double balloon enteroscopy needs sufficient sedation technique, because the
      examination is uncomfortable and lengthy. The most prevalent sedation method is
      conscious sedation world-wide. AIM: To demonstrate that double balloon
      enteroscopy examination can also be safely performed in general anesthesia with
      intubation and that this method can be an option in patients with severe multiple
      morbidities. METHODS: A retrospective evaluation of intubation narcosis in
      patients undergoing double balloon enteroscopy was performed at the 1st
      Department of Internal Medicine, Semmelweis University. Patients were grouped
      based on gender, age and physical state. Anesthesia records included the duration
      of anesthesia, the quantities of medications used and anesthesia-related
      complications. RESULTS: Data obtained from 108 general anesthesia cases were
      analyzed. There were no permanent anesthesia-related complications in the period
      examined. The most frequent side effects of anesthesia were hypotension (30.55%),
      desaturation (21.29%), and apnea (17.59%). These complications were significantly
      more frequent among patients with multiple morbidities; however, their incidence
      was not proportional with the quantity of the medications used or the duration of
      anesthesia. CONCLUSION: The findings confirm that the most important advantage of
      general anesthesia over other methods is that it ensures stable airways, which
      makes it easy to counter-act frequent complications such as desaturation, apnea
      and aspiration. The number of complications of anesthesia was higher among
      patients with multiple morbidities, but these complications could be easily
      overcome in all patient groups. Therefore, this method is highly recommended for
      patients with multiple morbidities. Intubation narcosis can be also a viable
      option of conscious sedation for patients without co-morbidities.

PMID- 21084250
TI  - [Attitude of patients and customers toward on-line purchase of drugs--a Hungarian
      survey by community pharmacies].
AB  - As internet is now available to nearly everyone in Hungary, the accessibility of
      websites offering pharmaceutical products is also increasing. The national and
      international regulation of these sites is currently an unsolved problem
      worldwide, thus potentially harmful, counterfeit and prescription only medicines
      are easily accessible on the market. We aimed to measure and estimate the current
      situation of the ordering of online medicines. In 5 Hungarian cities 434 self
      administered questionnaires were collected in community pharmacies. Our results
      show that 6.2% of the respondents have already ordered drugs or dietary
      supplements online and approximately same amount of people are considering this
      option in the near future. Based on our survey mostly the educated, the 30-49
      year old people and women are likely to buy drugs online. Every fifth respondent
      reported willingness to buy drugs online from abroad if lower prices were
      offered. Most people do not know that the quality of medicines purchased online
      could be different from the ones purchased from community pharmacies. We would
      like to draw attention of healthcare professionals to the rising popularity and
      potential risks of drugs available online.

PMID- 21084251
TI  - [Pure 46,XY gonadal dysgenesis].
AB  - The authors report a rare case of pure 46,XY gonadal dysgenesis (Swyer syndrome).
      Swyer syndrome is associated with 46,XY karyotype, primary amenorrhea as well as
      the presence of female internal genital tract and bilateral streak gonads in a
      phenotypic female. The genetic background of this syndrome includes mutations of
      several genes involved in the testis differentiation cascade. Mutation of the SRY
      gene accounts for only 10-15% of all 46,XY gonadal dysgenesis cases while the
      majority cases may be linked to other deficient genes involved in the sex
      differentiation pathway. The patient was a 16-year-old female who was referred
      for endocrinological evaluation because of primary amenorrhea. Physical
      examination revealed a phenotypic female, height 166 cm, weight: 56.5 kg, breast
      and pubic hair development were Tanner I. and II, respectively. She had female
      external genitalia. Pelvic magnetic resonance imaging showed a hypoplastic uterus
      and ovaries at both sides measuring 5*10 mm in size. Chromosomal analysis
      revealed 46,XY karyotype. Analysis of the SRY and SF1 genes showed no mutations.
      Serum follicle-stimulating hormone and luteinizing hormone were elevated. Serum
      tumor marker concentrations were normal. Prophylactic bilateral gonadectomy was
      performed and histological examination showed bilateral streak gonads. Hormone
      replacement therapy produced development of secondary sexual characters and 1.5
      years after treatment the patient had menarche. Authors conclude that karyotype
      analysis should be performed in adolescent with primary amenorrhea. After
      establishment of the diagnosis, dysgenetic gonads should be removed because of
      the high risk of gonadal neoplasia.

PMID- 21084252
TI  - [Traumatic Cesarean section].

PMID- 21084255
TI  - Analysis of quality of life of women in menopause period in Poland, Greece,
      Belarus and Belgium using MRS Scale. A multicenter study.
AB  - PURPOSE: The aim of this study was to compare the climacteric symptoms, the
      activity and quality of life of women in the menopausal period from Poland,
      Greece, Belarus and Belgium using a Menopause Rating Scale (MRS). MATERIAL AND
      METHODS: The study was conducted among women over 40 years of age, from Poland
      (241), Belorussia (119), Greece (100), and Belgium (79). For the purpose of this
      research, the Polish, Russian, Belgian and Greek versions of the MRS were used.
      The MRS Scoring scheme is simple, i.e. the score increases point by point with
      the increasing severity of subjectively perceived symptoms for each of the 11
      items (severity 0-no complaints, 4 scoring points-severe). The respondent
      provides her perception by checking one of 5 possible boxes of "severity" for
      each of the items. RESULTS: Mild or no complaints were reported to a similar
      extent by all women from these four countries. The intensity of the psychological
      symptoms was similar for the studied countries and did not differ significantly
      (P = 0.1531). Similar results we found in the somatic symptoms among the studied
      groups (P = 0.1421). A significant difference in the urogenital and sexual
      symptoms between Belgian and Belorussian women (P<0.001) was found. The frequency
      of menopausal symptoms was found to be significantly (P = 0.0381) higher among
      Belgian women in comparison to Belorussian ones. CONCLUSIONS: We found some
      differences between the menopausal complaints reported by women from Belgium,
      Belarus, Greece and Poland. Belgian women exhibited a more impaired quality of
      life due to a higher rate and severity of urogenital and sexual symptoms.

PMID- 21084254
TI  - Clinical utility of biochemical bone turnover markers in children and adolescents
      with osteosarcoma.
AB  - PURPOSE: Biochemical markers of bone turnover reflecting the intensity of all
      bone remodeling processes in skeleton are important for fast and non-invasive
      assessment of bone formation and resorption processes. They can be used in terms
      of both physiological and pathological states. The aim of this study was to
      investigate if bone metabolism markers can be clinically useful for monitoring of
      treatment in children and adolescents with osteosarcoma. MATERIAL/METHODS: The
      study consisted of 55 patients (median age 15 years) with osteosarcoma and 60
      healthy age matched counterparts. Serum bone turnover markers (bone alkaline
      phosphatase - BALP, osteocalcin - OC and C-terminal telopeptide of type I
      collagen - CTX) were analyzed by immunoenzymatic methods in patients at time of
      diagnosis, during treatment and after therapy. RESULTS: We observed that before
      treatment the concentration of OC in patients with osteosarcoma was significantly
      lower (p<0.05) compared to that obtained in healthy children, however, BALP and
      CTX were at a similar level. During chemotherapy the values of bone formation and
      resorption markers significantly decreased by about 20-30%. After therapy we
      observed different concentrations of all bone turnover markers in patients with
      favorable and unfavorable prognosis. Median values of OC and BALP were over
      twofold higher in patients with progression as compared to patients with
      remission of disease (p<0.01 and p<0.001, respectively). Patients with poor
      prognosis had also higher serum concentration of bone resorption marker in
      comparison to patients with remission (p<0.01). CONCLUSIONS: Presented results
      suggest that bone turnover markers identify changes in bone metabolism in
      patients with osteosarcoma during anticancer therapy. These markers due to the
      non-invasive methods and their specificity might be useful in monitoring of
      clinical treatment of osteosarcoma patients.

PMID- 21084256
TI  - Atopy patch test in the diagnosis of food allergy in children with
      gastrointestinal symptoms.
AB  - PURPOSE: To evaluate the diagnostic accuracy of the atopy patch test (APT) in
      detection of delayed-type sensitization to different food allergens, in children
      with digestive symptoms and with/or without cow's milk allergy. MATERIAL AND
      METHODS: 28 children suspected of food allergy-related gastrointestinal symptoms
      were underwent diagnostic procedures as skin prick test (SPT), specific
      immunoglobulin E (sIgE), APT, oral food challenge and then divided into two
      groups according to the results of oral food challenge: A - 17 children with
      cow's milk allergy, B - 11 children without cow's milk allergy. Sensitivity,
      specificity, positive (PPV) and negative (NPV) predictive values of APT were
      calculated. RESULTS: A positive challenge response to milk was found in 60,7% of
      examined children. No statistical difference in the prevalence of positive SPT
      and sIgE to milk has been found between the groups. The prevalence of positive
      APT to other food allergens was significantly higher in children with allergy to
      milk (p<0,005). No statistical difference of positive APT to other food allergens
      has been found in children with/or without cow's milk allergy. APT sensitivity
      and specificity in children with cow's milk allergy obtained on 77%/73%; where
      PPV obtained on 71%. CONCLUSIONS: High sensitivity and specificity of APT confirm
      its accuracy in diagnostics of delayed-type reactions in children with
      gastrointestinal symptoms. Combined atopy patch test and oral food challenge is
      essential for avoidance of unnecessary elimination diet. Delayed-type
      sensitization to other food allergens is common in children with cow's milk
      allergy.

PMID- 21084257
TI  - Abstracts of the 5th Congress of Update in Cardiology and Cardiovascular Surgery
      (UCCS), 25th-28th September 2009, Antalya, Turkey.

PMID- 21084258
TI  - Psychosocially influenced cancer: diverse early-life stress experiences and links
      to breast cancer.
AB  - This perspective on Boyd et al. (beginning on page 1398 in this issue of the
      journal) discusses recent published research examining the interplay between
      social stress and breast cancer. Cross-disciplinary studies using genetically
      defined mouse models and established neonatal and peripubertal paradigms of
      social stress are illuminating biological programming by diverse early-life
      experiences for the risk of breast cancer. Understanding the mechanisms
      underlying this programming can lead to the identification of risk factors and
      sensitive developmental windows, enabling improved prevention and treatment
      strategies for this devastating disease.

PMID- 21084259
TI  - Chemoprevention of pancreatic cancer: ready for the clinic?
AB  - Advances in our molecular, clinical, and epidemiologic understanding of the risk
      and development of pancreatic cancer offer hope for preventing this disease,
      which is largely intractable once developed. This perspective on provocative,
      genetically engineered mouse model work reported by Mohammed et al. (beginning on
      page 1417 in this issue of the journal) examines the prospects for pancreatic
      cancer chemoprevention with epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (TKI). Despite having limited value in advanced pancreatic
      cancer, EGFR TKIs show promise in the setting of early pancreatic carcinogenesis.

PMID- 21084260
TI  - Neonatal experiences differentially influence mammary gland morphology, estrogen
      receptor {alpha} protein levels, and carcinogenesis in BALB/c mice.
AB  - Prevention of breast cancer can be achieved with a better understanding of the
      factors contributing to normal breast development. Because the breast develops
      postnatally, alterations in the development and lifetime activity of the
      neuroendocrine system may set up an environment that increases cancer risk. The
      present study examined how two neonatal experiences over the first 3 weeks of
      life influence normal and malignant mammary gland development in female BALB/c
      mice. Following puberty, both brief (15 minutes) and prolonged (4 hours) daily
      maternal separations of newborn mice accelerated mammary gland development
      relative to nonseparated mice. Despite similar mammary gland morphologies between
      mice exposed to these two neonatal separation experiences, only mice exposed to
      prolonged maternal separation bouts showed a higher incidence and faster onset of
      mammary tumorigenesis following adulthood carcinogen [7,12
      dimethylbenz(a)anthracene] administration. Molecular analysis of estrogen
      receptor alpha (ERalpha) and p53, two proteins that have been implicated in
      breast cancer, revealed that for mice exposed to prolonged neonatal maternal
      separation bouts, mammary gland ERalpha protein levels were upregulated in a
      transcription-independent manner. On the other hand, p53 expression in mammary
      glands of adult mice was not differentially influenced by neonatal experiences.
      Our findings show that chronic, moderate psychosocial stress during the neonatal
      period increases the expression of ERalpha protein and promotes mammary
      tumorigenesis in adulthood.

PMID- 21084262
TI  - Chiari I malformation manifesting as bilateral trigeminal neuralgia: case report
      and review of the literature.

PMID- 21084261
TI  - The epidermal growth factor receptor inhibitor gefitinib prevents the progression
      of pancreatic lesions to carcinoma in a conditional LSL-KrasG12D/+ transgenic
      mouse model.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy
      with a dismal prognosis. Developing novel strategies to prevent or delay
      pancreatic cancer is currently of intense interest. The chemopreventive efficacy
      of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, was evaluated
      against the progression of pancreatic intraepithelial neoplasms (PanIN) to PDAC
      in conditional LSL-Kras(G12D/+) transgenic mice. LSL-Kras(G12D/+) and p48(Cre/+)
      mice were bred, and offspring of activated Kras(G12D/+) were generated. Six-week
      old male Kras(G12D/+) (20 per group) and C57BL/6 wild-type (12 per group) mice
      were fed (AIN-76A) diets containing 0, 100, and 200 ppm of gefitinib for 35
      weeks. At termination, pancreases were evaluated histopathologically for PanINs
      and PDAC, and various biomarkers were measured by immunohistochemistry,
      immunofluorescence, immunoblotting, and/or reverse transcription-PCR. Dietary
      gefitinib at 100 and 200 ppm significantly suppressed PDAC incidence by 77% and
      100%, respectively (P < 0.0001) when compared with control diet. Importantly, a
      significant inhibition of carcinoma and a dose-dependent suppression of PanINs
      [PanIN-1, 37-62% (P < 0.002); PanIN-2, 38-41 (P < 0.001); and PanIN-3, 7-34% (P <
      0.0141)] were observed in mice treated with gefitinib. Furthermore, mice treated
      with 100 and 200 ppm of gefitinib exhibited 67.6% to 77.3% of the pancreas to be
      free from ductal lesions. Also, gefitinib reduced EGFR, proliferating cell
      nuclear antigen, cyclin D1, C(2)GNT, RhoA, beta-catenin, p38, phospho
      extracellular signal-regulated kinase, caveolin-1, and mucin and increased cyclin
      B1 in the pancreatic lesions/PDAC. In summary, these results show that gefitinib
      can prevent the progression of pancreatic cancer precursor lesions to PDAC in a
      preclinical model. The present study highlights the promise of chemoprevention
      and the potential usefulness of EGFR inhibitors in individuals at high risk for
      pancreatic cancer.

PMID- 21084264
TI  - Intravenous thrombolysis for acute stroke in patients with cancer.

PMID- 21084263
TI  - What's in a name? Neuronal intermediate filament inclusion disease (NIFID),
      frontotemporal lobar degeneration-intermediate filament (FTLD-IF) or
      frontotemporal lobar degeneration-fused in sarcoma (FTLD-FUS)?

PMID- 21084265
TI  - Lack of antibody response to Guillain-Barre syndrome-related gangliosides in mice
      and men after novel flu vaccination.

PMID- 21084266
TI  - Risk of infection-related cancers after the loss of a child: a follow-up study in
      Sweden.
AB  - It is unknown whether severe emotional stress due to loss of a child influences
      the risk of cancers susceptible to immune modulation such as infection-related
      cancers. We conducted a historic cohort study in 1990 to 2004 on the basis of the
      Swedish Multi-Generation Register including 4,687,073 parents. Death of a child
      was identified through the Causes of Death Register. Poisson regression was used
      to derive the relative risks (RR) and 95% confidence intervals (CI) of infection
      related cancers, comparing the incidence rates of parents who lost a child with
      those who never lost a child. A total of 101,306 parents (2%) had lost a child
      during follow-up, among whom 1,608 subsequently developed infection-related
      cancers. After adjustment for age, sex, calendar year, educational level, and
      civil status, the overall RR of 14 cancers studied was 1.07 (95% CI: 1.02-1.12).
      Parents who lost a child were particularly at a higher risk for cancers
      potentially associated with human papilloma virus (HPV) infection such as
      cervical cancer (RR: 1.46; 95% CI: 1.17-1.80). Higher RRs for most cancers were
      obtained within 5 years after child loss and excess risk for liver and stomach
      cancers was confined to that period. No association was observed for lymphoma and
      nonmelanoma skin cancer at any time point after child loss. Although potential
      confounding by unmeasured factors cannot be ruled out, our findings lend support
      to the hypothesis that severe life stressors, such as child loss, may raise the
      risk for several, chiefly HPV-related, cancers.

PMID- 21084267
TI  - A dual PI3K/mTOR inhibitor, PI-103, cooperates with stem cell-delivered TRAIL in
      experimental glioma models.
AB  - The resistance of glioma cells to a number of antitumor agents and the highly
      invasive nature of glioma cells that escape the primary tumor mass are key
      impediments to the eradication of tumors in glioma patients. In this study, we
      evaluated the therapeutic efficacy of a novel PI3-kinase/mTOR inhibitor, PI-103,
      in established glioma lines and primary CD133(+) glioma-initiating cells and
      explored the potential of combining PI-103 with stem cell-delivered secretable
      tumor necrosis factor apoptosis-inducing ligand (S-TRAIL) both in vitro and in
      orthotopic mouse models of gliomas. We show that PI-103 inhibits proliferation
      and invasion, causes G(0)-G(1) arrest in cell cycle, and results in significant
      attenuation of orthotopic tumor growth in vivo. Establishing cocultures of neural
      stem cells (NSC) and glioma cells, we show that PI-103 augments the response of
      glioma cells to stem cell-delivered S-TRAIL. Using bimodal optical imaging, we
      show that when different regimens of systemic PI-103 delivery are combined with
      NSC-derived S-TRAIL, a significant reduction in tumor volumes is observed
      compared with PI-103 treatment alone. To our knowledge, this is the first study
      that reveals the antitumor effect of PI-103 in intracranial gliomas. Our findings
      offer a preclinical rationale for application of mechanism-based systemically
      delivered antiproliferative agents and novel stem cell-based proapoptotic
      therapies to improve treatment of malignant gliomas.

PMID- 21084268
TI  - In vivo antitumor activity of a recombinant IL-7/HGFbeta hybrid cytokine in mice.
AB  - The immune cytokine interleukin (IL)-7 and the beta-chain of hepatocyte growth
      factor (HGF) aggregate to form a naturally occurring heterodimer that stimulates
      the growth of common lymphoid progenitors and immature B and T lymphoid cells. We
      have cloned and expressed the heterodimer as a single-chain hybrid cytokine
      [recombinant (r) IL-7/HGFbeta], which stimulates short-term hematopoietic stem
      cells as well as lymphoid precursors. Inasmuch as IL-7 and HGF are known to have
      antitumor and protumor activities, respectively, we determined here whether
      either of these activities is exhibited by rIL-7/HGFbeta. We show that the in
      vivo administration of rIL-7/HGFbeta markedly inhibits the growth of newly
      initiated and established tumors and the formation of pulmonary metastases in
      murine models of colon cancer and melanoma. The antitumor effect of rIL-7/HGFbeta
      correlated with a marked increase in the number of tumor-infiltrating CD4(+) and
      CD8(+) T cells and activated dendritic cells. A major role for these immune cells
      in tumor suppression was indicated by the inability of rIL-7/HGFbeta to inhibit
      the growth of tumor cells in vitro and in congenitally athymic mice. Analysis of
      interferon-gamma-secreting T cells showed that the immune response was tumor
      specific. Our findings justify further evaluation of rIL-7/HGFbeta as a novel
      experimental cancer therapy.

PMID- 21084269
TI  - Cancer cells cut homophilic cell adhesion molecules and run.
AB  - The term contact inhibition (CI) encompasses the cellular changes that result in
      cessation of cell migration and of proliferation due to signals transduced when
      one cell comes into physical contact with another cell. Cancer cells, however, do
      not contact inhibit. A molecular understanding of the loss of CI in cancer cells
      is important for understanding tumor progression. In this Perspective, we propose
      that the loss of CI observed in cancer cells is the result of extracellular
      proteolysis of transmembrane cell-cell cell adhesion molecules (CAM) in the tumor
      microenvironment. Proteolysis of homophilic cell-cell CAMs results in a shed
      extracellular fragment and released cytoplasmic fragment(s) that disrupts
      adhesion and induces signals that promote proliferation and/or migration. The
      importance of this observation in tumor progression is supported by the presence
      of the shed extracellular fragments of homophilic cell-cell CAMs in serum and
      tumor tissue of cancer patients suggesting that instead of acting as tumor
      suppressors, the shed CAM extracellular and cytoplasmic fragments actually
      function as oncogenes. The study of cell-cell CAM cleavage will provide important
      and novel means of diagnosing, imaging, and treating tumor progression.

PMID- 21084271
TI  - VEGF-PET imaging is a noninvasive biomarker showing differential changes in the
      tumor during sunitinib treatment.
AB  - Non-invasive imaging of angiogenesis could ease the optimization of
      antiangiogenesis treatments for cancer. In this study, we evaluated the role of
      VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following
      treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment
      and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr
      ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft
      models of human cancer. The obtained imaging results were compared with tumor
      growth, VEGF plasma levels and immunohistologic analyzes. In contrast to (18)F
      FDG and (15)O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib
      treatment within the tumor with a strong decline in signal in the tumor center
      and only minimal reduction in tumor rim, with a pronounced rebound after
      sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and
      immunohistochemical vascular- and tumor- markers. Our findings highlight the
      strengths of VEGF-PET imaging to allow serial analysis of angiogenic changes in
      different areas within a tumor.

PMID- 21084270
TI  - A randomized clinical trial of the effects of supplemental calcium and vitamin D3
      on markers of their metabolism in normal mucosa of colorectal adenoma patients.
AB  - In cancer cell lines and rodent models, calcium and vitamin D favorably modulate
      cell proliferation, differentiation, and apoptosis in colonic epithelia. These
      effects may be modulated by local expression of the calcium receptor (CaR), the
      vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however,
      they have yet to be investigated in humans. To address this gap, we conducted a
      randomized, double-blinded, placebo-controlled 2*2 factorial clinical trial.
      Patients with at least one pathology-confirmed colorectal adenoma were treated
      with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6
      months (n=92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and
      distribution in biopsies of normal appearing rectal mucosa were detected by
      standardized, automated immunohistochemistry and quantified by image analysis. In
      the calcium-supplemented group, CaR expression increased 27% (P=0.03) and CYP24A1
      expression decreased 21% (P=0.79). In the vitamin D3-supplemented group, CaR
      expression increased 39% (P=0.01) and CYP27B1 expression increased 159% (P=0.06).
      In patients supplemented with both calcium and vitamin D3, VDR expression
      increased 19% (P=0.13) and CaR expression increased 24% (P=0.05). These results
      provide mechanistic support for further investigation of calcium and vitamin D3
      as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1,
      and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal
      neoplasms.

PMID- 21084272
TI  - Differential contextual responses of normal human breast epithelium to ionizing
      radiation in a mouse xenograft model.
AB  - Radiotherapy is a key treatment option for breast cancer, yet the molecular
      responses of normal human breast epithelial cells to ionizing radiation are
      unclear. A murine subcutaneous xenograft model was developed in which
      nonneoplastic human breast tissue was maintained with the preservation of normal
      tissue architecture, allowing us to study for the first time the radiation
      response of normal human breast tissue in situ. Ionizing radiation induced dose
      dependent p53 stabilization and p53 phosphorylation, together with the induction
      of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was
      stabilized in both luminal and basal cells, induction of Ser392-phosphorylated
      p53 and p21 was higher in basal cells and varied along the length of the ductal
      system. Basal breast epithelial cells expressed DeltaNp63, which was unchanged on
      irradiation. Although stromal responses themselves were minimal, the response of
      normal breast epithelium to ionizing radiation differed according to the stromal
      setting. We also demonstrated a dose-dependent induction of gamma-H2AX foci in
      epithelial cells that was similarly dependent on the stromal environment and
      differed between basal and luminal epithelial cells. The intrinsic differences
      between human mammary cell types in response to in vivo irradiation are
      consistent with clinical observation that therapeutic ionizing radiation is
      associated with the development of basal-type breast carcinomas. Furthermore,
      there may be clinically important stromal-epithelial interactions that influence
      DNA damage responses in the normal breast. These findings demonstrate highly
      complex responses of normal human breast epithelium following ionizing radiation
      exposure and emphasize the importance of studying whole-tissue effects rather
      than single-cell systems.

PMID- 21084273
TI  - An illegitimate microRNA target site within the 3' UTR of MDM4 affects ovarian
      cancer progression and chemosensitivity.
AB  - Overexpression of MDM4 (also known as MDMX or HDMX) is thought to promote
      tumorigenesis by decreasing p53 tumor suppressor function. Even modest decrease
      in Mdm4 levels affects tumorigenesis in mice, suggesting that genetic variants of
      MDM4 might have similar effects in humans. We sequenced the MDM4 gene in a series
      of ovarian cancer cell lines and carcinomas to identify mutations and/or single
      nucleotide polymorphisms (SNPs). We identified an SNP (SNP34091) in the 3'-UTR of
      MDM4 that creates a putative target site for hsa-miR-191, a microRNA that is
      highly expressed in normal and tumor tissues. Biochemical evidence supports
      specific miR-191-dependent regulation of the MDM4-C, but not MDM4-A, variant.
      Consistently, the A-allele was associated with statistically significant
      increased expression of MDM4 mRNA and protein levels in ovarian carcinomas.
      Importantly, the wild-type genotype (A/A) is more frequent (57.8% vs. 42.2% for
      A/C and C/C, respectively) in patients with high-grade carcinomas than in
      patients with low-grade carcinomas (47.2% vs. 52.5% for A/A and A/C + C/C,
      respectively). Moreover, A/A patients who do not express the estrogen receptor
      had a 4.2-fold [95% confidence interval (CI) = 1.2-13.5; P = 0.02] increased risk
      of recurrence and 5.5-fold (95% CI = 1.5-20.5; P = 0.01) increased risk of tumor
      related death. Unexpectedly, the frequency of p53 mutations was not significantly
      lower in A/A patients. We conclude that acquisition of an illegitimate miR-191
      target site causes downregulation of MDM4 expression, thereby significantly
      delaying ovarian carcinoma progression and tumor-related death. Importantly,
      these effects appear to be, at least partly, independent of p53.

PMID- 21084275
TI  - TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of
      melanoma bone metastases.
AB  - Melanoma often metastasizes to bone where it is exposed to high concentrations of
      TGF-beta. Constitutive Smad signaling occurs in human melanoma. Because TGF-beta
      promotes metastases to bone by several types of solid tumors including breast
      cancer, we hypothesized that pharmacologic blockade of the TGF-beta signaling
      pathway may interfere with the capacity of melanoma cells to metastasize to bone.
      In this study, we tested the effect of a small molecule inhibitor of TGF-beta
      receptor I kinase (TbetaRI), SD-208, on various parameters affecting the
      development and progression of melanoma, both in vitro and in a mouse model of
      human melanoma bone metastasis. In melanoma cell lines, SD-208 blocked TGF-beta
      induction of Smad3 phosphorylation, Smad3/4-specific transcription, Matrigel
      invasion and expression of the TGF-beta target genes PTHrP, IL-11, CTGF, and
      RUNX2. To assess effects of SD-208 on melanoma development and metastasis, nude
      mice were inoculated with 1205Lu melanoma cells into the left cardiac ventricle
      and drug was administered by oral gavage on prevention or treatment protocols. SD
      208 (60 mg/kg/d), started 2 days before tumor inoculation prevented the
      development of osteolytic bone metastases compared with vehicle. In mice with
      established bone metastases, the size of osteolytic lesions was significantly
      reduced after 4 weeks treatment with SD-208 compared with vehicle-treated mice.
      Our results demonstrate that therapeutic targeting of TGF-beta may prevent the
      development of melanoma bone metastases and decrease the progression of
      established osteolytic lesions.

PMID- 21084274
TI  - The BH3 mimetic ABT-737 induces cancer cell senescence.
AB  - ABT-737, a small molecule cell-permeable Bcl-2 antagonist that acts by mimicking
      BH3 proteins, induces apoptotic cell death in multiple cancer types. However,
      when incubated with this agent many solid tumor cell lines do not undergo
      apoptosis. The current study reveals a novel mechanism whereby ABT-737 when added
      to apoptosis-resistant cancer cells has profound biologic effects. In PV-10
      cells, a renal cell carcinoma that does not die after ABT-737 treatment, this
      agent induces a two-fold change in the transcription of nearly 430 genes. Many of
      these induced mRNA changes are in secreted proteins, IL-6, IL-8, and IL-11 and
      chemokines CXCL2 and CXCL5, or genes associated with an "inflammatory" phenotype.
      Strikingly, these gene changes are highly similar to those changes previously
      identified in cellular senescence. Brief exposure of apoptosis-resistant renal,
      lung and prostate cancer cell lines to ABT-737, although not capable of inducing
      cell death, causes the induction of senescence-associated beta-galactosidase and
      inhibition of cell growth consistent with the induction of cellular senescence.
      Evidence indicates that the induction of senescence occurs as a result of
      reactive oxygen species elevation followed by low-level activation of the caspase
      cascade, insufficient to induce apoptosis, but sufficient to lead to minor DNA
      damage and increases in p53, p21, IL-6 and 8 proteins. By overexpression of a
      dominant-negative p53 protein, we show that ABT-737-induced cellular senescence
      is p53-dependent. Thus, in multiple cancer types in which ABT-737 is incapable of
      causing cell death, ABT-737 may have additional cellular activities that make its
      use as an anticancer agent highly attractive.

PMID- 21084276
TI  - Autophagic survival in resistance to histone deacetylase inhibitors: novel
      strategies to treat malignant peripheral nerve sheath tumors.
AB  - Histone deacetylase inhibitors (HDACi) show promise as cancer therapeutics;
      however, the full scope of their utility remains unknown. Here we report findings
      that strongly rationalize clinical evaluation of HDACis in malignant peripheral
      nerve sheath tumors (MPNST), a class of highly aggressive, therapeutically
      resistant, and commonly fatal malignancies that occur sporadically or in patients
      with the inherited neurofibromatosis type-1 (NF1) syndrome. We evaluated the
      effects of the chemical HDACis PCI-24781, suberoylanilide hydroxamic acid, and MS
      275 on a panel of human NF1-associated and sporadic MPNSTs in vitro and in vivo.
      A subset of MPNSTs was found to be highly sensitive to HDACis, especially to PCI
      24781. All cell lines in this group were NF1-associated. Significant proapoptotic
      effects were noted in vitro and in vivo and were independent of p53 mutational
      status. In contrast, as a group the sporadic-MPNST cells were markedly resistant
      to HDACi treatment. HDACis were found to induce productive autophagy in MPNST
      cells. Genetic and/or pharmacologic autophagy blockade resulted in significant
      HDACi-induced apoptosis in cells defined as resistant or sensitive, leading to
      abrogated growth of primary tumors and lung metastases in tumor xenograft assays.
      Among autophagy-associated genes expressed in response to HDACi, the immunity
      related GTPase family, M was validated as a critical target in mediating HDACi
      induced autophagy and enhanced apoptosis. Taken together, our findings strongly
      support the evaluation of HDACi currently in clinical trials as an important new
      therapeutic strategy to treat MPNST, including in combination with autophagy
      blocking combination regimens in particular for patients with sporadic MPNST.

PMID- 21084278
TI  - Biological activity of 4-substituted methoxybenzoyl-aryl-thiazole: an active
      microtubule inhibitor.
AB  - Formation of microtubules is a dynamic process that involves polymerization and
      depolymerization of alphabeta-tubulin heterodimers. Drugs that enhance or inhibit
      tubulin polymerization can destroy this dynamic process, arresting cells in the
      G(2)/M phase of the cell cycle. Although drugs that target tubulin generally
      demonstrate cytotoxic potency in the subnanomolar range, resistance due to drug
      efflux is a common phenomenon among the antitubulin agents. We recently reported
      a class of 4-substituted methoxybenzoyl-aryl-thiazoles (SMART) that exhibited
      great in vitro potency and broad spectrum cellular cytotoxicity. Evaluation of
      the in vitro and in vivo anticancer activities of 3 SMART compounds, SMART-H (H),
      SMART-F (F), and SMART-OH (OH), with varying substituents at the 4-position of
      aryl ring, demonstrated that they bind potently to the colchicine-binding site in
      tubulin, inhibit tubulin polymerization, arrest cancer cells in G(2)/M phase of
      the cell cycle, and induce their apoptosis. The SMART compounds also equipotently
      inhibit the growth of parental and MDR-overexpressing cells in vitro, indicating
      that they can overcome multidrug resistance. In vivo antitumor efficacy studies
      in human prostate (PC-3) and melanoma (A375) cancer xenograft models demonstrated
      that SMART-H and SMART-F treatments resulted in %T/C values ranging from 4% to
      30%. In addition, in vivo SMART-H treatment for 21 days at the higher dose (15
      mg/kg) failed to produce any apparent neurotoxicity. These studies provide the
      first in vivo evidence and proof-of-concept that SMART compounds are similarly
      efficacious to currently FDA approved antitubulin drugs for cancer treatment, but
      they can circumvent P-glycoprotein-mediated drug resistance.

PMID- 21084277
TI  - Phosphatase PRL-3 is a direct regulatory target of TGFbeta in colon cancer
      metastasis.
AB  - Metastasis causes most deaths from cancer yet mechanistic understanding and
      therapeutic options remain limited. Overexpression of the phosphatase PRL-3
      (phosphatase of regenerating liver) is associated with metastasis of colon
      cancer. Here, we show that PRL-3 is a direct target of signaling by TGFbeta,
      which is broadly implicated in progression and metastasis. We found that
      suppression of PRL-3 expression by TGFbeta was mediated by Smad-dependent
      inhibition of PRL-3 transcription at the level of promoter activity. PRL-3
      activation stimulated PI3K/AKT signaling that caused resistance to stress-induced
      apoptosis. PRL-3 overexpression promoted metastatic colonization in an orthotopic
      mouse model of colon cancer, whereas PRL-3 knockdown reduced metastatic
      potential. Altered metastatic phenotypes were not derivative of primary tumor
      development or local invasion but could be attributed to PRL-3-mediated cell
      survival. Our findings suggest that inhibiting PRL-3 expression might be an
      important mechanism through which TGFbeta suppresses metastasis in colon cancer.
      In addition, our findings suggest that loss of TGFbeta signaling, which occurs
      commonly during colon cancer progression, is sufficient to activate a PRL-3
      mediated cell survival pathway that can selectively promote metastasis.
      Therefore, a major implication of our findings is that PRL-3 antagonists may
      offer significant value for antimetastatic therapy in patients with colon cancer.

PMID- 21084279
TI  - BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex
      with the Rho effector kinase ROCK2.
AB  - BRCA2 germline mutations account for the majority of heredity breast and ovarian
      cancer. Besides its role in DNA damage repair, BRCA2 also plays an important role
      in cytokinesis, transcription regulation, and cancer cell proliferation.
      Recently, we reported that BRCA2 localizes to centrosomes as well as nuclei and
      the dysfunction of BRCA2 in a centrosome causes abnormalities in cell division.
      Here, we identified a nucleolar phosphoprotein, nucleophosmin (NPM), as a novel
      BRCA2-associated protein. We also detected the binding of BRCA2 to ROCK2, an
      effector of Rho small GTPase. Because it is known that ROCK2 binds to NPM at
      centrosomes, these 3 proteins may form a complex. NPM-binding region was within
      amino acids 639-1,000 of BRCA2. Exogenous expression of this BRCA2 region
      resulted in aberrant centrosome amplification and a high frequency of
      multinucleated cells. Our results suggested that a complex consisting of BRCA2,
      NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell
      division and that dysfunction of this regulation might be involved in the
      tumorigenesis of breast cancer.

PMID- 21084280
TI  - High-resolution X-ray analysis reveals binding of arginine to aromatic residues
      of lysozyme surface: implication of suppression of protein aggregation by
      arginine.
AB  - While biotechnological applications of arginine (Arg) as a solution additive that
      prevents protein aggregation are increasing, the molecular mechanism of its
      effects remains unclear. In this study, we investigated the Arg-lysozyme complex
      by high-resolution crystallographic analysis. Three Arg molecules were observed
      to be in close proximity to aromatic amino acid residues of the protein surface,
      and their occupancies gradually increased with increasing Arg concentration.
      These interactions were mediated by electrostatic, hydrophobic and cation-pi
      interactions with the surface residues. The binding of Arg decreased the
      accessible surface area of aromatic residues by 40%, but increased that of
      charged residues by 10%. These changes might prevent intermolecular hydrophobic
      interactions by shielding hydrophobic regions of the lysozyme surface, resulting
      in an increase in protein solubility.

PMID- 21084281
TI  - A brief perspective of the determination of crystal structures of site-directed
      mutants of tyrosyl-tRNA synthetase.
AB  - Rapid determination of the three-dimensional structures of mutant proteins is so
      highly embedded within the discipline of protein engineering that it almost seems
      a routine part of the process of analyzing mutant function. However, in the early
      days of protein engineering, the time and energy involved in determining mutant
      structures were substantial compared with today and the dividends unclear. Here
      is a brief perspective on the determination of the first crystal structures of
      site-directed mutants of the tyrosyl-tRNA synthetase--an enzyme used to establish
      many of the early principles of protein engineering.

PMID- 21084282
TI  - Dissecting the molecular determinants of ligand-binding-induced macromolecular
      switching using thermodynamic cycles.
AB  - The energetic networks that govern regulated switching processes in
      macromolecules are poorly understood at a molecular level. We illustrate a
      general methodology that uses thermodynamic cycles to measure the coupling
      energetics between specific groups in a macromolecule and ligand-binding-induced
      macromolecular switching. The approach is applied to new and published
      thermodynamic stability and/or binding data not previously analyzed in this way,
      for a wide range of switching systems, including H+ or Ca2+-binding-induced
      myristoyl switching, ion or peptide-binding-induced conformational switching in
      various proteins and small molecule binding to a ribo-switch. The results show
      how this powerful approach can be used to identify and dissect the molecular
      determinants of switching in macromolecules.

PMID- 21084283
TI  - Surface supercharged human enteropeptidase light chain shows improved solubility
      and refolding yield.
AB  - Enteropeptidase is a serine protease used in different biotechnological
      applications. For many applications the smaller light chain can be used to avoid
      the expression of the rather large holoenzyme. Recombinant human enteropeptidase
      light chain (hEPL) shows high activity but low solubility and refolding yields,
      currently limiting its use in biotechnological applications. Here we describe
      several protein modifications that lead to improved solubility and refolding
      yield of human hEPL whilst retaining the enzyme activity. Specifically, protein
      surface supercharging (N6D, G21D, G22D, N141D, K209E) of the protein increased
      the solubility more than 100-fold. Replacement of a free cysteine residue with
      serine (C112S) improved the refolding yield by 50%. The heat stability of this
      C112S variant was also significantly improved by supercharging. This study shows
      that even mild protein surface supercharging can have pronounced effects on
      protein solubility and stability.

PMID- 21084284
TI  - SESAME (SEquence Sorter & AMplicon Explorer): genotyping based on high-throughput
      multiplex amplicon sequencing.
AB  - SUMMARY: Characterizing genetic diversity through genotyping short amplicons is
      central to evolutionary biology. Next-generation sequencing (NGS) technologies
      changed the scale at which these type of data are acquired. SESAME is a web
      application package that assists genotyping of multiplexed individuals for
      several markers based on NGS amplicon sequencing. It automatically assigns reads
      to loci and individuals, corrects reads if standard samples are available and
      provides an intuitive graphical user interface (GUI) for allele validation based
      on the sequences and associated decision-making tools. The aim of SESAME is to
      help allele identification among a large number of sequences. AVAILABILITY:
      SESAME and its documentation are freely available under the Creative Commons
      Attribution-NonCommercial-ShareAlike 3.0 Unported Licence for Windows and Linux
      from http://www1.montpellier.inra.fr/CBGP/NGS/ or http://tinyurl.com/ngs-sesame.

PMID- 21084285
TI  - Structural and functional comparison of the RING domains of two p53 E3 ligases,
      Mdm2 and Pirh2.
AB  - The tumor suppressor p53 maintains genome stability and prevents malignant
      transformation by promoting cell cycle arrest and apoptosis. Both Mdm2 and Pirh2
      have been shown to ubiquitylate p53 through their RING domains, thereby targeting
      p53 for proteasomal degradation. Using structural and functional analyses, here
      we show that the Pirh2 RING domain differs from the Mdm2 RING domain in its
      oligomeric state, surface charge distribution, and zinc coordination scheme.
      Pirh2 also possesses weaker E3 ligase activity toward p53 and directs ubiquitin
      to different residues on p53. NMR and mutagenesis studies suggest that whereas
      Pirh2 and Mdm2 share a conserved E2 binding site, the seven C-terminal residues
      of the Mdm2 RING directly contribute to Mdm2 E3 ligase activity, a feature unique
      to Mdm2 and absent in the Pirh2 RING domain. This comprehensive analysis of the
      Pirh2 and Mdm2 RING domains provides structural and mechanistic insight into p53
      regulation by its E3 ligases.

PMID- 21084286
TI  - Structural and biophysical analysis of BST-2/tetherin ectodomains reveals an
      evolutionary conserved design to inhibit virus release.
AB  - BST-2/tetherin is a host antiviral molecule that functions to potently inhibit
      the release of enveloped viruses from infected cells. In return, viruses have
      evolved antagonists to this activity. BST-2 traps budding virions by using two
      separate membrane-anchoring regions that simultaneously incorporate into the host
      and viral membranes. Here, we detailed the structural and biophysical properties
      of the full-length BST-2 ectodomain, which spans the two membrane anchors. The
      1.6-A crystal structure of the complete mouse BST-2 ectodomain reveals an ~145-A
      parallel dimer in an extended alpha-helix conformation that predominantly forms a
      coiled coil bridged by three intermolecular disulfides that are required for
      stability. Sequence analysis in the context of the structure revealed an
      evolutionarily conserved design that destabilizes the coiled coil, resulting in a
      labile superstructure, as evidenced by solution x-ray scattering displaying bent
      conformations spanning 150 and 180 A for the mouse and human BST-2 ectodomains,
      respectively. Additionally, crystal packing analysis revealed possible curvature
      sensing tetrameric structures that may aid in proper placement of BST-2 during
      the genesis of viral progeny. Overall, this extended coiled-coil structure with
      inherent plasticity is undoubtedly necessary to accommodate the dynamics of viral
      budding while ensuring separation of the anchors.

PMID- 21084287
TI  - Somatic cell plasticity and Niemann-Pick type C2 protein: fibroblast activation.
AB  - A growing body of evidence points toward activated fibroblasts, also known as
      myofibroblasts, as one of the leading mediators in several major human
      pathologies including proliferative fibrotic disorders, invasive tumor growth,
      rheumatoid arthritis, and atherosclerosis. Niemann-Pick Type C2 (NPC2) protein
      has been recently identified as a product of the second gene in NPC disease. It
      encodes ubiquitous, highly conserved, secretory protein with the poorly defined
      function. Here we show that NPC2 deficiency in human fibroblasts confers their
      activation. The activation phenomenon was not limited to fibroblasts as it was
      also observed in aortic smooth muscle cells upon silencing NPC2 gene by siRNA.
      More importantly, activated synovial fibroblasts isolated from patients with
      rheumatoid arthritis were also identified as NPC2-deficient at both the NPC2 mRNA
      and protein levels. The molecular mechanism responsible for activation of NPC2
      null cells was shown to be a sustained phosphorylation of ERK 1/2 mitogen
      activated protein kinase (MAPK), which fulfills both the sufficient and necessary
      fibroblast activation criteria. All of these findings highlight a novel mechanism
      where NPC2 by negatively regulating ERK 1/2 MAPK phosphorylation may efficiently
      suppress development of maladaptive tissue remodeling and inflammation.

PMID- 21084289
TI  - Molecular characterization of a novel geranylgeranyl pyrophosphate synthase from
      Plasmodium parasites.
AB  - We present here a study of a eukaryotic trans-prenylsynthase from the malaria
      pathogen Plasmodium vivax. Based on the results of biochemical assays and
      contrary to previous indications, this enzyme catalyzes the production of
      geranylgeranyl pyrophosphate (GGPP) rather than farnesyl pyrophosphate (FPP).
      Structural analysis shows that the product length is constrained by a hydrophobic
      cavity formed primarily by a set of residues from the same subunit as the product
      as well as at least one other from the dimeric partner. Furthermore, Plasmodium
      GGPP synthase (GGPPS) can bind nitrogen-containing bisphosphonates (N-BPs)
      strongly with the energetically favorable cooperation of three Mg(2+), resulting
      in inhibition by this class of compounds at IC(50) concentrations below 100 nM.
      In contrast, human and yeast GGPPSs do not accommodate a third magnesium atom in
      the same manner, resulting in their insusceptibility to N-BPs. This
      differentiation is in part attributable to a deviation in a conserved motif known
      as the second aspartate-rich motif: whereas the aspartates at the start and end
      of the five-residue motif in FFPP synthases and P. vivax GGPPSs both participate
      in the coordination of the third Mg(2+), an asparagine is featured as the last
      residue in human and yeast GGPPSs, resulting in a different manner of interaction
      with nitrogen-containing ligands.

PMID- 21084288
TI  - Caveolin-3 regulates protein kinase A modulation of the Ca(V)3.2 (alpha1H) T-type
      Ca2+ channels.
AB  - Voltage-gated T-type Ca(2+) channel Ca(v)3.2 (alpha(1H)) subunit, responsible for
      T-type Ca(2+) current, is expressed in different tissues and participates in
      Ca(2+) entry, hormonal secretion, pacemaker activity, and arrhythmia. The precise
      subcellular localization and regulation of Ca(v)3.2 channels in native cells is
      unknown. Caveolae containing scaffolding protein caveolin-3 (Cav-3) localize many
      ion channels, signaling proteins and provide temporal and spatial regulation of
      intracellular Ca(2+) in different cells. We examined the localization and
      regulation of the Ca(v)3.2 channels in cardiomyocytes. Immunogold labeling and
      electron microscopy analysis demonstrated co-localization of the Ca(v)3.2 channel
      and Cav-3 relative to caveolae in ventricular myocytes. Co-immunoprecipitation
      from neonatal ventricular myocytes or transiently transfected HEK293 cells
      demonstrated that Ca(v)3.1 and Ca(v)3.2 channels co-immunoprecipitate with Cav-3.
      GST pulldown analysis confirmed that the N terminus region of Cav-3 closely
      interacts with Ca(v)3.2 channels. Whole cell patch clamp analysis demonstrated
      that co-expression of Cav-3 significantly decreased the peak Ca(v)3.2 current
      density in HEK293 cells, whereas co-expression of Cav-3 did not alter peak
      Ca(v)3.1 current density. In neonatal mouse ventricular myocytes, overexpression
      of Cav-3 inhibited the peak T-type calcium current (I(Ca,T)) and adenovirus
      (AdCa(v)3.2)-mediated increase in peak Ca(v)3.2 current, but did not affect the L
      type current. The protein kinase A-dependent stimulation of I(Ca,T) by 8-Br-cAMP
      (membrane permeable cAMP analog) was abolished by siRNA directed against Cav-3.
      Our findings on functional modulation of the Ca(v)3.2 channels by Cav-3 is
      important for understanding the compartmentalized regulation of Ca(2+) signaling
      during normal and pathological processes.

PMID- 21084291
TI  - The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the
      phosphorylated form of the immunomodulating agent FTY720.
AB  - FTY720 is a novel immunomodulating drug that can be phosphorylated inside cells;
      its phosphorylated form, FTY720-P, binds to a sphingosine 1-phosphate (S1P)
      receptor, S1P(1), and inhibits lymphocyte egress into the circulating blood.
      Although the importance of its pharmacological action has been well recognized,
      little is known about how FTY720-P is released from cells after its
      phosphorylation inside cells. Previously, we showed that zebrafish Spns2 can act
      as an S1P exporter from cells and is essential for zebrafish heart formation.
      Here, we demonstrate that human SPNS2 can transport several S1P analogues,
      including FTY720-P. Moreover, FTY720-P is transported by SPNS2 through the same
      pathway as S1P. This is the first identification of an FTY720-P transporter in
      cells; this finding is important for understanding FTY720 metabolism.

PMID- 21084290
TI  - Low extracellular pH induces damage in the pancreatic acinar cell by enhancing
      calcium signaling.
AB  - Low extracellular pH (pHe) occurs in a number of clinical conditions and
      sensitizes to the development of pancreatitis. The mechanisms responsible for
      this sensitization are unknown. Because abnormal Ca(2+) signaling underlies many
      of the early steps in the pathogenesis of pancreatitis, we evaluated the effect
      of decreasing pHe from 7.4 to 7.0 on Ca(2+) signals in the acinar cell. Low pHe
      significantly increased the amplitude of cerulein-induced Ca(2+) signals. The
      enhancement in amplitude was localized to the basolateral region of the acinar
      cell and was reduced by pretreatment with ryanodine receptor (RYR) inhibitors.
      Because basolateral RYRs also have been implicated in the pathogenesis of
      pancreatitis, we evaluated the effects of RYR inhibitors on pancreatitis
      responses in acidic conditions. RYR inhibitors significantly reduced the
      sensitizing effects of low pHe on zymogen activation and cellular injury. These
      findings suggest that enhanced RYR-mediated Ca(2+) signaling in the basolateral
      region of the acinar cell is responsible for the injurious effects of low pHe on
      the exocrine pancreas.

PMID- 21084292
TI  - Alkoxy-auxins are selective inhibitors of auxin transport mediated by PIN, ABCB,
      and AUX1 transporters.
AB  - Polar auxin movement is a primary regulator of programmed and plastic plant
      development. Auxin transport is highly regulated at the cellular level and is
      mediated by coordinated transport activity of plasma membrane-localized PIN,
      ABCB, and AUX1/LAX transporters. The activity of these transporters has been
      extensively analyzed using a combination of pharmacological inhibitors, synthetic
      auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin
      dependent growth in other species that are less tractable to genetic manipulation
      require more selective inhibitors than are currently available. In this report,
      we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3
      acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that
      the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action
      in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic
      responses associated with asymmetric auxin distribution in Arabidopsis and maize.
      The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB
      proteins expressed in yeast. However, these analogs did not inhibit or activate
      SCF(TIR1) auxin signaling and had no effect on the subcellular trafficking of PIN
      proteins. Together these results indicate that alkoxy-auxins are inactive auxin
      analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin
      transport proteins. Alkoxy-auxins are powerful new tools for analyses of auxin
      dependent development.

PMID- 21084293
TI  - Recognition of transcription termination signal by the nuclear polyadenylated RNA
      binding (NAB) 3 protein.
AB  - Non-coding RNA polymerase II transcripts are processed by the poly(A)-independent
      termination pathway that requires the Nrd1 complex. The Nrd1 complex includes two
      RNA-binding proteins, the nuclear polyadenylated RNA-binding (Nab) 3 and the
      nuclear pre-mRNA down-regulation (Nrd) 1 that bind their specific termination
      elements. Here we report the solution structure of the RNA-recognition motif
      (RRM) of Nab3 in complex with a UCUU oligonucleotide, representing the Nab3
      termination element. The structure shows that the first three nucleotides of UCUU
      are accommodated on the beta-sheet surface of Nab3 RRM, but reveals a sequence
      specific recognition only for the central cytidine and uridine. The specific
      contacts we identified are important for binding affinity in vitro as well as for
      yeast viability. Furthermore, we show that both RNA-binding motifs of Nab3 and
      Nrd1 alone bind their termination elements with a weak affinity. Interestingly,
      when Nab3 and Nrd1 form a heterodimer, the affinity to RNA is significantly
      increased due to the cooperative binding. These findings are in accordance with
      the model of their function in the poly(A) independent termination, in which
      binding to the combined and/or repetitive termination elements elicits efficient
      termination.

PMID- 21084294
TI  - Structure and function of APH(4)-Ia, a hygromycin B resistance enzyme.
AB  - The aminoglycoside phosphotransferase (APH) APH(4)-Ia is one of two enzymes
      responsible for bacterial resistance to the atypical aminoglycoside antibiotic
      hygromycin B (hygB). The crystal structure of APH(4)-Ia enzyme was solved in
      complex with hygB at 1.95 A resolution. The APH(4)-Ia structure adapts a general
      two-lobe architecture shared by other APH enzymes and eukaryotic kinases, with
      the active site located at the interdomain cavity. The enzyme forms an extended
      hydrogen bond network with hygB primarily through polar and acidic side chain
      groups. Individual alanine substitutions of seven residues involved in hygB
      binding did not have significant effect on APH(4)-Ia enzymatic activity,
      indicating that the binding affinity is spread across a distributed network. hygB
      appeared as the only substrate recognized by APH(4)-Ia among the panel of 14
      aminoglycoside compounds. Analysis of the active site architecture and the
      interaction with the hygB molecule demonstrated several unique features
      supporting such restricted substrate specificity. Primarily the APH(4)-Ia
      substrate-binding site contains a cluster of hydrophobic residues that provides a
      complementary surface to the twisted structure of the substrate. Similar to
      APH(2") enzymes, the APH(4)-Ia is able to utilize either ATP or GTP for
      phosphoryl transfer. The defined structural features of APH(4)-Ia interactions
      with hygB and the promiscuity in regard to ATP or GTP binding could be exploited
      for the design of novel aminoglycoside antibiotics or inhibitors of this enzyme.

PMID- 21084295
TI  - Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic
      shuttling of mammalian translation initiation factor eIF6.
AB  - Eukaryotic initiation factor 6 (eIF6), a highly conserved protein from yeast to
      mammals, is essential for 60 S ribosome biogenesis and assembly. Both yeast and
      mammalian eIF6 are phosphorylated at Ser-174 and Ser-175 by the nuclear isoform
      of casein kinase 1 (CK1). The molecular basis of eIF6 phosphorylation, however,
      remains elusive. In the present work, we show that subcellular distribution of
      eIF6 in the nuclei and the cytoplasm of mammalian cells is mediated by
      dephosphorylation and phosphorylation, respectively. This nucleo-cytoplasmic
      shuttling is dependent on the phosphorylation status at Ser-174 and Ser-175 of
      eIF6. We demonstrate that Ca(2+)-activated calcineurin phosphatase binds to and
      promotes nuclear localization of eIF6. Increase in intracellular concentration of
      Ca(2+) leads to rapid translocation of eIF6 from the cytoplasm to the nucleus, an
      event that is blocked by specific calcineurin inhibitors cyclosporin A or FK520.
      Nuclear export of eIF6 is regulated by phosphorylation at Ser-174 and Ser-175 by
      the nuclear isoform of CK1. Mutation of eIF6 at the phosphorylatable Ser-174 and
      Ser-175 to alanine or treatment of cells with the CK1 inhibitor, D4476 inhibits
      nuclear export of eIF6 and results in nuclear accumulation of eIF6. Together,
      these results establish eIF6 as a substrate for calcineurin and suggest a novel
      paradigm for calcineurin function in 60 S ribosome biogenesis via regulating the
      nuclear accumulation of eIF6.

PMID- 21084296
TI  - Structure and catalysis of acylaminoacyl peptidase: closed and open subunits of a
      dimer oligopeptidase.
AB  - Acylaminoacyl peptidase from Aeropyrum pernix is a homodimer that belongs to the
      prolyl oligopeptidase family. The monomer subunit is composed of one hydrolase
      and one propeller domain. Previous crystal structure determinations revealed that
      the propeller domain obstructed the access of substrate to the active site of
      both subunits. Here we investigated the structure and the kinetics of two mutant
      enzymes in which the aspartic acid of the catalytic triad was changed to alanine
      or asparagine. Using different substrates, we have determined the pH dependence
      of specificity rate constants, the rate-limiting step of catalysis, and the
      binding of substrates and inhibitors. The catalysis considerably depended both on
      the kind of mutation and on the nature of the substrate. The results were
      interpreted in terms of alterations in the position of the catalytic histidine
      side chain as demonstrated with crystal structure determination of the native and
      two mutant structures (D524N and D524A). Unexpectedly, in the homodimeric
      structures, only one subunit displayed the closed form of the enzyme. The other
      subunit exhibited an open gate to the catalytic site, thus revealing the
      structural basis that controls the oligopeptidase activity. The open form of the
      native enzyme displayed the catalytic triad in a distorted, inactive state. The
      mutations affected the closed, active form of the enzyme, disrupting its
      catalytic triad. We concluded that the two forms are at equilibrium and the
      substrates bind by the conformational selection mechanism.

PMID- 21084297
TI  - Distinct roles of the active-site Mg2+ ligands, Asp882 and Asp705, of DNA
      polymerase I (Klenow fragment) during the prechemistry conformational
      transitions.
AB  - DNA polymerases catalyze the incorporation of deoxynucleoside triphosphates into
      a growing DNA chain using a pair of Mg(2+) ions, coordinated at the active site
      by two invariant aspartates, whose removal by mutation typically reduces the
      polymerase activity to barely detectable levels. Using two stopped-flow
      fluorescence assays that we developed previously, we have investigated the role
      of the carboxylate ligands, Asp(705) and Asp(882), of DNA polymerase I (Klenow
      fragment) in the early prechemistry steps that prepare the active site for
      catalysis. We find that neither carboxylate is required for an early
      conformational transition, reported by a 2-aminopurine probe, that takes place in
      the open ternary complex after binding of the complementary dNTP. However, the
      subsequent fingers-closing step requires Asp(882); this step converts the open
      ternary complex into the closed conformation, creating the active-site geometry
      required for catalysis. Crystal structures indicate that the Asp(882) position
      changes very little during fingers-closing; this side chain may therefore serve
      as an anchor point to receive the dNTP-associated metal ion as the nucleotide is
      delivered into the active site. The Asp(705) carboxylate is not required until
      after the fingers-closing step, and we suggest that its role is to facilitate the
      entry of the second Mg(2+) into the active site. The two early prechemistry steps
      that we have studied take place normally at very low Mg(2+) concentrations,
      although higher concentrations are needed for covalent nucleotide addition,
      consistent with the second metal ion entering the ternary complex after fingers
      closing.

PMID- 21084298
TI  - TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated
      chloride channel conductance in airway and intestinal epithelial cells.
AB  - TMEM16A (ANO1) functions as a calcium-activated chloride channel (CaCC). We
      developed pharmacological tools to investigate the contribution of TMEM16A to
      CaCC conductance in human airway and intestinal epithelial cells. A screen of
      ~110,000 compounds revealed four novel chemical classes of small molecule TMEM16A
      inhibitors that fully blocked TMEM16A chloride current with an IC(50) < 10 MUM,
      without interfering with calcium signaling. Following structure-activity
      analysis, the most potent inhibitor, an aminophenylthiazole (T16A(inh)-A01), had
      an IC(50) of ~1 MUM. Two distinct types of inhibitors were identified. Some
      compounds, such as tannic acid and the arylaminothiophene CaCC(inh)-A01, fully
      inhibited CaCC current in human bronchial and intestinal cells. Other compounds,
      including T16A(inh)-A01 and digallic acid, inhibited total CaCC current in these
      cells poorly, but blocked mainly an initial, agonist-stimulated transient
      chloride current. TMEM16A RNAi knockdown also inhibited mainly the transient
      chloride current. In contrast to the airway and intestinal cells, all TMEM16A
      inhibitors fully blocked CaCC current in salivary gland cells. We conclude that
      TMEM16A carries nearly all CaCC current in salivary gland epithelium, but is a
      minor contributor to total CaCC current in airway and intestinal epithelia. The
      small molecule inhibitors identified here permit pharmacological dissection of
      TMEM16A/CaCC function and are potential development candidates for drug therapy
      of hypertension, pain, diarrhea, and excessive mucus production.

PMID- 21084299
TI  - Dematin, a component of the erythrocyte membrane skeleton, is internalized by the
      malaria parasite and associates with Plasmodium 14-3-3.
AB  - The malaria parasite invades the terminally differentiated erythrocytes, where it
      grows and multiplies surrounded by a parasitophorous vacuole. Plasmodium blood
      stages translocate newly synthesized proteins outside the parasitophorous vacuole
      and direct them to various erythrocyte compartments, including the cytoskeleton
      and the plasma membrane. Here, we show that the remodeling of the host cell
      directed by the parasite also includes the recruitment of dematin, an actin
      binding protein of the erythrocyte membrane skeleton and its repositioning to the
      parasite. Internalized dematin was found associated with Plasmodium 14-3-3, which
      belongs to a family of conserved multitask molecules. We also show that, in
      vitro, the dematin-14-3-3 interaction is strictly dependent on phosphorylation of
      dematin at Ser(124) and Ser(333), belonging to two 14-3-3 putative binding
      motifs. This study is the first report showing that a component of the
      erythrocyte spectrin-based membrane skeleton is recruited by the malaria parasite
      following erythrocyte infection.

PMID- 21084300
TI  - Processing of the synaptic cell adhesion molecule neurexin-3beta by Alzheimer
      disease alpha- and gamma-secretases.
AB  - Neurexins (NRXNs) are synaptic cell adhesion molecules having essential roles in
      the assembly and maturation of synapses into fully functional units.
      Immunocytochemical and electrophysiological studies have shown that specific
      binding across the synaptic cleft of the ectodomains of presynaptic NRXNs and
      postsynaptic neuroligins have the potential to bidirectionally coordinate and
      trigger synapse formation. Moreover, in vivo studies as well as genome-wide
      association studies pointed out implication of NRXNs in the pathogenesis of
      cognitive disorders including autism spectrum disorders and different types of
      addictions including opioid and alcohol dependences, suggesting an important role
      in synaptic function. Despite extensive investigations, the mechanisms by which
      NRXNs modulate the properties of synapses remain largely unknown. We report here
      that alpha- and gamma-secretases can sequentially process NRXN3beta, leading to
      the formation of two final products, an ~80-kDa N-terminal extracellular domain
      of Neurexin-3beta (sNRXN3beta) and an ~12-kDa C-terminal intracellular NRXN3beta
      domain (NRXN3beta-ICD), both of them being potentially implicated in the
      regulation of NRXNs and neuroligins functions at the synapses or in yet
      unidentified signal transduction pathways. We further report that this processing
      is altered by several PS1 mutations in the catalytic subunit of the gamma
      secretase that cause early-onset familial Alzheimer disease.

PMID- 21084301
TI  - HES1 (hairy and enhancer of split 1) is a determinant of bone mass.
AB  - HES1 (hairy and enhancer of split) is a transcription factor that regulates
      osteoblastogenesis in vitro. The skeletal effects of HES1 misexpression were
      studied. Transgenic mice where a 3.6-kilobase fragment of the collagen type 1
      alpha1 promoter directs HES1 overexpression were created. Transgenics were
      osteopenic due to decreased osteoblast function in female and increased bone
      resorption in male mice. HES1 impaired osteoblastogenesis in vitro, and
      transgenic osteoblasts enhanced the resorptive activity of co-cultured osteoclast
      precursors. Mice homozygous for a Hes1 loxP-targeted allele were bred to
      transgenics, where the paired-related homeobox gene enhancer or the osteocalcin
      promoter direct Cre recombinase expression to inactivate Hes1 in the limb bud or
      in osteoblasts. To avoid genetic compensation, Hes1 was inactivated in the
      context of the global deletion of Hes3 and Hes5. Hes3 and Hes5 null mice had no
      skeletal phenotype. Hes1 inactivation in the limb bud increased femoral length
      and trabecular number. Hes1 inactivation in osteoblasts increased trabecular bone
      volume, number, and connectivity due to increased mineral apposition rate and
      suppressed bone resorption. Hes1 inactivation in vitro increased alkaline
      phosphatase expression and suppressed the resorptive activity of co-cultured
      osteoclast precursors. In conclusion, by inhibiting osteoblast function and
      inducing bone resorption, HES1 is an intracellular determinant of bone mass and
      structure.

PMID- 21084302
TI  - N-cadherin cell-cell adhesion complexes are regulated by fibronectin matrix
      assembly.
AB  - Fibronectin is a principal component of the extracellular matrix. Soluble
      fibronectin molecules are assembled into the extracellular matrix as insoluble,
      fibrillar strands via a cell-dependent process. In turn, the interaction of cells
      with the extracellular matrix form of fibronectin stimulates cell functions
      critical for tissue repair. Cross-talk between cell-cell and cell-extracellular
      matrix adhesion complexes is essential for the organization of cells into
      complex, functional tissue during embryonic development and tissue remodeling.
      Here, we demonstrate that fibronectin matrix assembly affects the organization,
      composition, and function of N-cadherin-based adherens junctions. Using
      fibronectin-null mouse embryonic myofibroblasts, we identified a novel quaternary
      complex composed of N-cadherin, beta-catenin, tensin, and actin that exists in
      the absence of a fibronectin matrix. In the absence of fibronectin, homophilic N
      cadherin ligation recruited both tensin and alpha5beta1 integrins into nascent
      cell-cell adhesions. Initiation of fibronectin matrix assembly disrupted the
      association of tensin and actin with N-cadherin, released alpha5beta1 integrins
      and tensin from cell-cell contacts, stimulated N-cadherin reorganization into
      thin cellular protrusions, and decreased N-cadherin adhesion. Fibronectin matrix
      assembly has been shown to recruit alpha5beta1 integrins and tensin into
      fibrillar adhesions. Taken together, these studies suggest that tensin serves as
      a common cytoskeletal link for integrin- and cadherin-based adhesions and that
      the translocation of alpha5beta1 integrins from cell-cell contacts into fibrillar
      adhesions during fibronectin matrix assembly is a novel mechanism by which cell
      cell and cell-matrix adhesions are coordinated.

PMID- 21084303
TI  - Intracellular ubiquitylation of the epithelial Na+ channel controls extracellular
      proteolytic channel activation via conformational change.
AB  - The epithelial Na(+) channel ENaC is a key player in the maintenance of whole
      body Na(+) balance, and consequently of blood pressure. It is tightly regulated
      by numerous signaling pathways including ubiquitylation via the ubiquitin-protein
      ligase Nedd4-2. This mechanism is itself under the control of several kinases,
      which phosphorylate Nedd4-2, thereby interfering with ENaC/Nedd4-2 interaction,
      or by Usp2-45, which binds to and deubiquitylates ENaC. Another, different
      regulatory mechanism concerns the proteolytic activation of ENaC, during which
      the channel is cleaved on its luminal side by intracellular convertases such as
      furin, and further activated by extracellular proteases such as CAP-1. This
      process is regulated as well but the underlying mechanisms are not understood.
      Previously, evidence was provided that the ubiquitylation status of ENaC may
      affect the cleavage of the channel. When ubiquitylation of ENaC was reduced,
      either by co-expressing Usp2-45, or mutating either the ENaC PY-motifs (i.e. the
      binding sites for Nedd4-2) or intracellular lysines (i.e. ubiquitylation sites),
      the level of channel cleavage was increased. Here we demonstrate that lysine
      mutated ENaC channels are not ubiquitylated at the cell surface, are
      preferentially cleaved, and Usp2-45 does not affect their cleavage efficiency. We
      further show by limited proteolysis that the intracellular ubiquitylation status
      of ENaC affects the extracellular conformation of alphaENaC, by demonstrating
      that non-ubiquitylated channels are more efficiently cleaved when treated with
      extracellularly added trypsin or chymotrypsin. These results present a new
      paradigm in which an intracellular, post-translational modification (e.g.
      ubiquitylation) of a transmembrane protein can affect its extracellular
      conformation.

PMID- 21084304
TI  - Cell-based analysis of structure-function activity of threonine aspartase 1.
AB  - Taspase1 is a threonine protease responsible for cleaving intracellular
      substrates. As such, (de)regulated Taspase1 function is expected not only to be
      vital for ordered development but may also be relevant for disease. However, the
      full repertoires of Taspase1 targets as well as the exact biochemical
      requirements for its efficient and substrate-specific cleavage are not yet
      resolved. Also, no cellular assays for this protease are currently available,
      hampering the exploitation of the (patho)biological relevance of Taspase1. Here,
      we developed highly efficient cell-based translocation biosensor assays to probe
      Taspase1 trans-cleavage in vivo. These modular sensors harbor variations of
      Taspase1 cleavage sites and localize to the cytoplasm. Expression of Taspase1 but
      not of inactive Taspase1 mutants or of unrelated proteases triggers proteolytic
      cleavage and nuclear accumulation of the biosensors. Employing our assay combined
      with scanning mutagenesis, we identified the sequence and spatial requirements
      for efficient Taspase1 processing in liquid and solid tumor cell lines.
      Collectively, our results defined an improved Taspase1 consensus recognition
      sequence, Q(3)(F/I/L/V)(2)D(1)?G(1)'X(2)'D(3)'D(4)', allowing the first genome
      wide bioinformatic identification of the human Taspase1 degradome. Among the 27
      most likely Taspase1 targets are cytoplasmic but also nuclear proteins, such as
      the upstream stimulatory factor 2 (USF2) or the nuclear RNA export factors 2/5
      (NXF2/5). Cleavage site recognition and proteolytic processing of selected
      targets were verified in the context of the biosensor and for the full-length
      proteins. We provide novel mechanistic insights into the function and bona fide
      targets of Taspase1 allowing for a focused investigation of the (patho)biological
      relevance of this type 2 asparaginase.

PMID- 21084305
TI  - Danthron functions as a retinoic X receptor antagonist by stabilizing tetramers
      of the receptor.
AB  - Retinoic X receptor (RXR) is a promising target for drug discovery against cancer
      and metabolic syndromes. Here, we identified a specific RXRalpha antagonist,
      danthron, from the traditional Chinese medicine rhubarb. Danthron repressed all
      tested RXRalpha-involved response element transcription, including the RXRE,
      PPRE, FXRE, and LXRE. Results from native PAGE and isothermal titration
      calorimetry (ITC)-based assays indicated that danthron bound to the tetrameric
      RXRalpha-LBD in a specific stoichimetric ratio, and such a binding could
      influence the corepressor SMRT affinity to the receptor. Additionally, a unique
      tetrameric structure of the apo-RXRalpha ligand-binding domain (LBD) was
      determined, which exhibited a larger tetramer interface and different ligand
      binding pocket size compared with the one previously reported. Together with the
      biochemical and biophysical results, the determined crystal structure of danthron
      soaked RXRalpha-LBD suggested a new mechanism for danthron antagonism to
      tetrameric RXRalpha. Moreover, the in vivo efficient improvement of insulin
      sensitivity by danthron was observed in diet-induced obese (DIO) mice. Thus, our
      findings were expected to supply new insights into the structural basis of
      RXRalpha antagonist for its further potential therapeutic application.

PMID- 21084306
TI  - Streptolysin S contributes to group A streptococcal translocation across an
      epithelial barrier.
AB  - Group A Streptococcus pyogenes (GAS) is a human pathogen that causes local
      suppurative infections and severe invasive diseases. Systemic dissemination of
      GAS is initiated by bacterial penetration of the epithelial barrier of the
      pharynx or damaged skin. To gain insight into the mechanism by which GAS
      penetrates the epithelial barrier, we sought to identify both bacterial and host
      factors involved in the process. Screening of a transposon mutant library of a
      clinical GAS isolate recovered from an invasive episode allowed identification of
      streptolysin S (SLS) as a novel factor that facilitates the translocation of GAS.
      Of note, the wild type strain efficiently translocated across the epithelial
      monolayer, accompanied by a decrease in transepithelial electrical resistance and
      cleavage of transmembrane junctional proteins, including occludin and E-cadherin.
      Loss of integrity of intercellular junctions was inhibited after infection with a
      deletion mutant of the sagA gene encoding SLS, as compared with those infected
      with the wild type strain. Interestingly, following GAS infection, calpain was
      recruited to the plasma membrane along with E-cadherin. Moreover, bacterial
      translocation and destabilization of the junctions were partially inhibited by a
      pharmacological calpain inhibitor or genetic interference with calpain. Our data
      indicate a potential function of SLS that facilitates GAS invasion into deeper
      tissues via degradation of epithelial intercellular junctions in concert with the
      host cysteine protease calpain.

PMID- 21084307
TI  - Analysis of the polymerization initiation and activity of Pasteurella multocida
      heparosan synthase PmHS2, an enzyme with glycosyltransferase and UDP-sugar
      hydrolase activity.
AB  - Heparosan synthase catalyzes the polymerization of heparosan (-4GlcUAbeta1
      4GlcNAcalpha1-)(n) by transferring alternatively the monosaccharide units from
      UDP-GlcUA and UDP-GlcNAc to an acceptor molecule. Details on the heparosan chain
      initiation by Pasteurella multocida heparosan synthase PmHS2 and its influence on
      the polymerization process have not been reported yet. By site-directed
      mutagenesis of PmHS2, the single action transferases PmHS2-GlcUA(+) and PmHS2
      GlcNAc(+) were obtained. When incubated together in the standard polymerization
      conditions, the PmHS2-GlcUA(+)/PmHS2-GlcNAc(+) showed comparable polymerization
      properties as determined for PmHS2. We investigated the first step occurring in
      heparosan chain initiation by the use of the single action transferases and by
      studying the PmHS2 polymerization process in the presence of heparosan templates
      and various UDP-sugar concentrations. We observed that PmHS2 favored the
      initiation of the heparosan chains when incubated in the presence of an excess of
      UDP-GlcNAc. It resulted in a higher number of heparosan chains with a lower
      average molecular weight or in the synthesis of two distinct groups of heparosan
      chain length, in the absence or in the presence of heparosan templates,
      respectively. These data suggest that PmHS2 transfers GlcUA from UDP-GlcUA moiety
      to a UDP-GlcNAc acceptor molecule to initiate the heparosan polymerization; as a
      consequence, not only the UDP-sugar concentration but also the amount of each UDP
      sugar is influencing the PmHS2 polymerization process. In addition, it was shown
      that PmHS2 hydrolyzes the UDP-sugars, UDP-GlcUA being more degraded than UDP
      GlcNAc. However, PmHS2 incubated in the presence of both UDP-sugars favors the
      synthesis of heparosan polymers over the hydrolysis of UDP-sugars.

PMID- 21084308
TI  - Basement membrane deposition of nidogen 1 but not nidogen 2 requires the nidogen
      binding module of the laminin gamma1 chain.
AB  - The nidogen-laminin interaction is proposed to play a key role in basement
      membrane (BM) assembly. However, though there are similarities, the phenotypes in
      mice lacking nidogen 1 and 2 (nidogen double null) differ to those of mice
      lacking the nidogen binding module (gamma1III4) of the laminin gamma1 chain. This
      indicates different cell- and tissue-specific functions for nidogens and their
      interaction with laminin and poses the question of whether the phenotypes in
      nidogen double null mice are caused by the loss of the laminin-nidogen
      interaction or rather by other unknown nidogen functions. To investigate this, we
      analyzed BMs, in particular those in the skin of mice lacking the nidogen binding
      module. In contrast to nidogen double null mice, all skin BMs in gamma1III4
      deficient mice appeared normal. Furthermore, although nidogen 1 deposition was
      strongly reduced, nidogen 2 appeared unchanged. Mice with additional deletion of
      the laminin gamma3 chain, which contains a gamma1-like nidogen binding module,
      showed a further reduction of nidogen 1 in the dermoepidermal BM; however, this
      again did not affect nidogen 2. This demonstrates that in vivo only nidogen 1
      deposition is critically dependent on the nidogen binding modules of the laminin
      gamma1 and gamma3 chains, whereas nidogen 2 is independently recruited either by
      binding to an alternative site on laminin or to other BM proteins.

PMID- 21084309
TI  - The role of Cys-298 in aldose reductase function.
AB  - Diabetic tissues are enriched in an "activated" form of human aldose reductase
      (hAR), a NADPH-dependent oxidoreductase involved in sugar metabolism. Activated
      hAR has reduced sensitivity to potential anti-diabetes drugs. The C298S mutant of
      hAR reproduces many characteristics of activated hAR, although it differs from
      wild-type hAR only by the replacement of a single sulfur atom with oxygen.
      Isothermal titration calorimetry measurements revealed that the binding constant
      of NADPH to the C298S mutant is decreased by a factor of two, whereas that of
      NADP(+) remains the same. Similarly, the heat capacity change for the binding of
      NADPH to the C298S mutant is twice increased; however, there is almost no
      difference in the heat capacity change for binding of the NADP(+) to the C298S. X
      ray crystal structures of wild-type and C298S hAR reveal that the side chain of
      residue 298 forms a gate to the nicotinamide pocket and is more flexible for
      cysteine compared with serine. Unlike Cys-298, Ser-298 forms a hydrogen bond with
      Tyr-209 across the nicotinamide ring, which inhibits movements of the
      nicotinamide. We hypothesize that the increased polarity of the oxidized
      nicotinamide weakens the hydrogen bond potentially formed by Ser-298, thus,
      accounting for the relatively smaller effect of the mutation on NADP(+) binding.
      The effects of the mutant on catalytic rate constants and binding constants for
      various substrates are the same as for activated hAR. It is, thus, further
      substantiated that activated hAR arises from oxidative modification of Cys-298, a
      residue near the nicotinamide binding pocket.

PMID- 21084310
TI  - Characterization of a binding site for anionic phospholipids on KCNQ1.
AB  - The KCNQ family of potassium channels underlie a repolarizing K(+) current in the
      heart and the M-current in neurones. The assembly of KCNQ1 with KCNE1 generates
      the delayed rectifier current I(Ks) in the heart. Characteristically these
      channels are regulated via G(q/11)-coupled receptors and the inhibition seen
      after phospholipase C activation is now thought to occur from membrane
      phosphatidylinositol (4,5)-bisphosphate (PIP(2)) depletion. It is not clear how
      KCNQ1 recognizes PIP(2) and specifically which residues in the channel complex
      are important. Using biochemical techniques we identify a cluster of basic
      residues namely, Lys-354, Lys-358, Arg-360, and Lys-362, in the proximal C
      terminus as being involved in binding anionic phospholipids. The mutation of
      specific residues in combination, to alanine leads to the loss of binding to
      phosphoinositides. Functionally, the introduction of these mutations into KCNQ1
      leads to shifts in the voltage dependence of channel activation toward
      depolarized potentials and reductions in current density. Additionally, the
      biophysical effects of the charge neutralizing mutations, which disrupt
      phosphoinositide binding, mirror the effects we see on channel function when we
      deplete cellular PIP(2) levels through activation of a G(q/11)-coupled receptor.
      Conversely, the addition of diC8-PIP(2) to the wild-type channel, but not a
      PIP(2) binding-deficient mutant, acts to shift the voltage dependence of channel
      activation toward hyperpolarized potentials and increase current density. In
      conclusion, we use a combined biochemical and functional approach to identify a
      cluster of basic residues important for the binding and action of anionic
      phospholipids on the KCNQ1/KCNE1 complex.

PMID- 21084311
TI  - Calcium-sensing receptor decreases cell surface expression of the inwardly
      rectifying K+ channel Kir4.1.
AB  - The Ca(2+)-sensing receptor (CaR) regulates salt and water transport in the
      kidney as demonstrated by the association of gain of function CaR mutations with
      a Bartter syndrome-like, salt-wasting phenotype, but the precise mechanism for
      this effect is not fully established. We found previously that the CaR interacts
      with and inactivates an inwardly rectifying K(+) channel, Kir4.1, which is
      expressed in the distal nephron that contributes to the basolateral K(+)
      conductance, and in which loss of function mutations are associated with a
      complex phenotype that includes renal salt wasting. We now find that CaR
      inactivates Kir4.1 by reducing its cell surface expression. Mutant CaRs reduced
      Kir4.1 cell surface expression and current density in HEK-293 cells in proportion
      to their signaling activity. Mutant, activated Galpha(q) reduced cell surface
      expression and current density of Kir4.1, and these effects were blocked by RGS4,
      a protein that blocks signaling via Galpha(i) and Galpha(q). Other alpha subunits
      had insignificant effects. Knockdown of caveolin-1 blocked the effect of
      Galpha(q) on Kir4.1, whereas knockdown of the clathrin heavy chain had no effect.
      CaR had no comparable effect on the renal outer medullary K(+) channel, an apical
      membrane distal nephron K(+) channel that is internalized by clathrin-coated
      vesicles. Co-immunoprecipitation studies showed that the CaR and Kir4.1
      physically associate with caveolin-1 in HEK cells and in kidney extracts. Thus,
      the CaR decreases cell surface expression of Kir4.1 channels via a mechanism that
      involves Galpha(q) and caveolin. These results provide a novel molecular basis
      for the inhibition of renal NaCl transport by the CaR.

PMID- 21084312
TI  - Product-assisted catalysis as the basis of the reaction specificity of threonine
      synthase.
AB  - Threonine synthase (TS), which is a pyridoxal 5'-phosphate (PLP)-dependent
      enzyme, catalyzes the elimination of the gamma-phosphate group from O-phospho-L
      homoserine (OPHS) and the subsequent addition of water at Cbeta to form L
      threonine. The catalytic course of TS is the most complex among the PLP enzymes,
      and it is an intriguing problem how the elementary steps are controlled in TS to
      carry out selective reactions. When L-vinylglycine was added to Thermus
      thermophilus HB8 TS in the presence of phosphate, L-threonine was formed with
      k(cat) and reaction specificity comparable with those when OPHS was used as the
      substrate. However, in the absence of phosphate or when sulfate was used in place
      of phosphate, only the side reaction product, alpha-ketobutyrate, was formed.
      Global analysis of the spectral changes in the reaction of TS with L-threonine
      showed that compared with the more acidic sulfate ion, the phosphate ion
      decreased the energy levels of the transition states of the addition of water at
      the Cbeta of the PLP-alpha-aminocrotonate aldimine (AC) and the transaldimination
      to form L-threonine. The x-ray crystallographic analysis of TS complexed with an
      analog for AC gave a distinct electron density assigned to the phosphate ion
      derived from the solvent near the Cbeta of the analog. These results indicated
      that the phosphate ion released from OPHS by gamma-elimination acts as the base
      catalyst for the addition of water at Cbeta of AC, thereby providing the basis of
      the reaction specificity. The phosphate ion is also considered to accelerate the
      protonation/deprotonation at Cgamma.

PMID- 21084313
TI  - Carbon-11-Pittsburgh compound B positron emission tomography imaging of amyloid
      deposition in presenilin 1 mutation carriers.
AB  - (11)Carbon-Pittsburgh compound B positron emission tomography studies have
      suggested early and prominent amyloid deposition in the striatum in presenilin 1
      mutation carriers. This cross-sectional study examines the (11)Carbon-Pittsburgh
      compound B positron emission tomography imaging profiles of presymptomatic and
      mildly affected (mini-mental state examination >= 20) carriers of seven
      presenilin 1 mutations, comparing them with groups of controls and symptomatic
      sporadic Alzheimer's disease cases. Parametric ratio images representing
      (11)Carbon-Pittsburgh compound B retention from 60 to 90 min were created using
      the pons as a reference region and nine regions of interest were studied. We
      confirmed that increased amyloid load may be detected in presymptomatic
      presenilin 1 mutation carriers with (11)Carbon-Pittsburgh compound B positron
      emission tomography and that the pattern of retention is heterogeneous.
      Comparison of presenilin 1 and sporadic Alzheimer's disease groups revealed
      significantly greater thalamic retention in the presenilin 1 group and
      significantly greater frontotemporal retention in the sporadic Alzheimer's
      disease group. A few individuals with presenilin 1 mutations showed increased
      cerebellar (11)Carbon-Pittsburgh compound B retention suggesting that this region
      may not be as suitable a reference region in familial Alzheimer's disease.

PMID- 21084316
TI  - Calculating the test-retest reliability co-efficient from normative retest data
      for determining reliable change.

PMID- 21084315
TI  - Mechanism of anthracycline-mediated down-regulation of GATA4 in the heart.
AB  - AIMS: Anthracyclines such as daunorubicin (DNR) and doxorubicin are effective
      cancer chemotherapeutic agents, but can induce cardiotoxicity. GATA4 has been
      shown to serve as a survival factor of cardiac muscle cells, and anthracyclines
      promote apoptosis in part by down-regulating GATA4. The present study
      investigated the mechanism of anthracycline action to down-regulate GATA4.
      METHODS AND RESULTS: DNR inhibited the transcriptional activity exhibited by the
      250 bp conserved region immediately upstream from the transcriptional start site
      of the Gata4 gene. Mapping this region identified that the CCAAT-binding
      factor/nuclear factor-Y (CBF/NF-Y) binding to the CCAAT box was inhibited by DNR
      in HL-1 cardiac muscle cells and in perfused isolated mouse hearts. The DNR
      action on the Gata4 promoter was found to be dependent on p53, since DNR promoted
      nuclear binding of p53 to CBF/NF-Y and pifithrin-alpha (a p53 inhibitor)
      attenuated DNR down-regulation of GATA4. CONCLUSION: Anthracycline down
      regulation of GATA4 is mediated by the inhibition of Gata4 gene transcription via
      a novel mechanism that involves the p53-dependent inhibition of CBF/NF-Y binding
      to the CCAAT box within the Gata4 promoter.

PMID- 21084317
TI  - Response to: Are we teaching our students what they need to know about ageing?
      Results from the UK National Survey of Undergraduate Teaching in Ageing and
      Geriatric Medicine.

PMID- 21084314
TI  - Up-regulation of ectopic trypsins in the myocardium by influenza A virus
      infection triggers acute myocarditis.
AB  - AIMS: Influenza A virus (IAV) infection markedly up-regulates ectopic trypsins in
      various organs, viral envelope glycoprotein processing proteases, which are pre
      requisites for virus entry and multiplication. We investigated the pathological
      roles of trypsin up-regulation in the progression of IAV-induced myocarditis,
      cytokine induction, and viral replication in the hearts, and also investigated
      the protective effects of trypsin inhibitor on cardiac dysfunction in vivo and
      selective knockdown of trypsin on IAV-induced cellular damage in cardiomyoblasts.
      METHODS AND RESULTS: The relationship of the expression among IAV RNA, trypsins,
      matrix metalloproteinase (MMP)-9, MMP-2, pro-inflammatory cytokines interleukin
      (IL)-6, IL-1beta, and tumour necrosis factor-alpha was analysed in mice hearts
      and cardiomyoblasts after IAV infection. The severity of myocarditis was most
      noticeable during Day 6-9 post-infection, along with peak expression of viral
      RNA, trypsins, particularly trypsin2, MMPs, and cytokines. Cardiac ATP levels
      were the lowest at Day 9. Up-regulated trypsins, viral protein, and tissue
      injured loci in the myocardium were closely localized. Trypsin inhibitor
      aprotinin treatment in vivo and selective trypsin1- and trypsin2-knockdown,
      particularly the latter, in H9c2 cardiomyoblasts significantly suppressed viral
      replication, up-regulation of MMPs, and production of active MMP-9 and cytokines,
      resulting in marked protection against cellular damage, ATP depletion, and
      apoptosis. IAV infection-induced cardiac dysfunction monitored by
      echocardiography was improved significantly by aprotinin treatment. CONCLUSIONS:
      IAV-induced trypsins, particularly trypsin2, in the myocardium trigger acute
      viral myocarditis through stimulation of IAV replication, proMMP-9 activation,
      and cytokine induction. These results suggest that up-regulation of trypsins is
      one of the key host pathological findings in IAV-induced myocarditis.

PMID- 21084318
TI  - Langerhans cell histiocytosis: old disease new treatment.
AB  - Langerhans cell histiocytosis (LCH) has been previously thought of as a rare
      illness, but is now increasingly diagnosed as a result of the more intensive
      investigations of patients with cystic pulmonary disease. In recent years,
      treatments developed from our new understanding of the molecular biology of
      malignant disease have been applied to patients with LCH, and responses seen. In
      this review, we describe the origins, presentation and modern treatment of LCH,
      showing that there is new hope for patients with this condition.

PMID- 21084319
TI  - Hepatic schistosomiasis.

PMID- 21084320
TI  - Adherence to standards of care by health maintenance organizations in Israel and
      the USA.
AB  - BACKGROUND: The health-care systems in the USA and Israel differ in organization,
      financing and expenditure levels. However, managed care organizations play an
      important role in both countries, and a comparison of the performance of their
      community-based health plans could inform policymakers about ways to improve the
      quality of care. OBJECTIVE: To compare the adherence to standards of care in
      Israel and in the USA. STUDY DESIGN: An observational study comparing trends in
      performance using data from reports of the National Quality Measures Program in
      Israel and of the National Committee for Quality Assurance in the USA. RESULTS:
      Differences in specifications preclude a comparison between most measures in the
      two reports. However, the comparison of 11 similar measures in the 2007 reports
      indicates that performance was higher in the USA by 10 or more percentage points
      on four measures (flu immunization, medication for asthma, screening for
      colorectal cancer and monitoring for diabetic nephropathy). Performance was
      higher in Israel on three measures in patients with diabetes (blood pressure, low
      density lipoprotein (LDL) cholesterol and glycemic control), and similar on the
      remaining four measures. Between 2005 and 2007, quality of care improved in both
      countries. However, improvement was slower in the USA than in Israel.
      CONCLUSIONS: In comparison with the USA, Israel achieves comparable health
      maintenance organization (HMO) quality on several primary care indicators and
      more rapid quality improvement, despite its substantially lower level of
      expenditure. Considering the differences between the two countries in settings
      and populations, further research is needed to assess the causes,
      generalizability and policy implications of these findings.

PMID- 21084322
TI  - What motivates professionals to engage in the accreditation of healthcare
      organizations?
AB  - OBJECTIVE: Motivated staff are needed to improve quality and safety in healthcare
      organizations. Stimulating and engaging staff to participate in accreditation
      processes is a considerable challenge. The purpose of this study was to explore
      the experiences of health executives, managers and frontline clinicians who
      participated in organizational accreditation processes: what motivated them to
      engage, and what benefits accrued? DESIGN/PARTICIPANTS: The setting was a large
      public teaching hospital undergoing a planned review of its accreditation status.
      A research protocol was employed to conduct semi-structured interviews with a
      purposive sample of 30 staff with varied organizational roles, from different
      professions, to discuss their involvement in accreditation. Thematic analysis of
      the data was undertaken. RESULTS: The analysis identified three categories, each
      with sub-themes: accreditation response (reactions to accreditation and the value
      of surveys); survey issues (participation in the survey, learning through
      interactions and constraints) and documentation issues (self-assessment report,
      survey report and recommendations). Participants' occupational role focuses their
      attention to prioritize aspects of the accreditation process. Their motivations
      to participate and the benefits that accrue to them can be positively self
      reinforcing. Participants have a desire to engage collaboratively with colleagues
      to learn and validate their efforts to improve. CONCLUSION: Participation in the
      accreditation process promoted a quality and safety culture that crossed
      organizational boundaries. The insights into worker motivation can be applied to
      engage staff to promote learning, overcome organizational boundaries and improve
      services. The findings can be applied to enhance involvement with accreditation
      and, more broadly, to other quality and safety activities.

PMID- 21084321
TI  - Risk factors for hospital-acquired 'poor glycemic control': a case-control study.
AB  - OBJECTIVE: To determine the patient and hospital characteristics associated with
      severe manifestations of 'poor glycemic control'-a 'no-pay' hospital-acquired
      condition defined by the US Medicare program based on hospital claims related to
      severe complications of diabetes. DESIGN: A nested case-control study. SETTING:
      California acute care hospitals from 2005 to 2006. PARTICIPANTS: All cases (n=
      261) with manifestations of poor glycemic control not present on admission
      admitted to California acute care hospitals from 2005 to 2006 and 261 controls
      were matched (1:1) using administrative data for age, sex, major diagnostic
      category and severity of illness. MAIN OUTCOME MEASURE(S): The adjusted odds
      ratio (OR) for experiencing poor glycemic control. RESULTS: Deaths (16 vs. 9%, P=
      0.01) and total costs ($26,125 vs. $18,233, P= 0.026) were significantly higher
      among poor glycemic control cases. Risk-adjusted conditional logistic regression
      revealed that each additional chronic condition increased the odds of poor
      glycemic control by 12% (OR: 1.12, 95% CI: 1.04-1.22). The interaction of
      registered nurse staffing and hospital teaching status suggested that in non
      teaching hospitals, each additional nursing hour per adjusted patient day
      significantly reduced the odds of poor glycemic control by 16% (OR: 0.84, 95% CI:
      0.73-0.96). Nurse staffing was not significant in teaching hospitals (OR: 0.98,
      95% CI: 0.88-1.11). CONCLUSIONS: Severe poor glycemic control complications are
      relatively rare but meaningful events with disproportionately high costs and
      mortality. Increasing nurse staffing may be an effective strategy in reducing
      poor glycemic control complications particularly in non-teaching hospitals.

PMID- 21084323
TI  - Using an enhanced oral chemotherapy computerized provider order entry system to
      reduce prescribing errors and improve safety.
AB  - OBJECTIVE: To reduce the probability of failure in the oral chemotherapy order,
      review and administration process and to reduce oral chemotherapy-related
      prescribing errors intercepted by clinical pharmacists prior to reaching the
      patient. DESIGN: A before-and-after cohort study. SETTING: A 719-bed
      multidisciplinary tertiary care institution with a pediatric division and an
      outpatient cancer center. PARTICIPANTS: A multidisciplinary team characterized
      key elements of the oral chemotherapy process using healthcare failure modes and
      effects analysis (HFMEA). INTERVENTION(S): Oral chemotherapy computerized
      provider order entry (CPOE) was developed and implemented. MAIN OUTCOME
      MEASURE(S): Pharmacist-intercepted oral chemotherapy prescribing errors over a 24
      month period (before) and over a 6-month period (after) were analyzed according
      to the error type (errors in clinical decision making, errors in transcription or
      errors related to prescribing policy). The incidence of prescribing errors prior
      to and following CPOE implementation was compared by calculating the odds ratio
      (OR) and the 95% confidence interval (CI). RESULTS: HFMEA hazard analysis
      revealed seven potential failure modes, with the highest hazard scores in the
      prescribing and administration components of the process. CPOE implementation
      significantly (P= 0.023) reduced prescribing error risk by 69% [OR (95% CI) =
      0.31 (0.11-0.86)] and eliminated certain types of errors that can lead to
      significant patient harm. CONCLUSIONS: Prescribing oral chemotherapy is a failure
      mode with significant risk of inducing patient harm. CPOE is effective in
      reducing prescribing errors of oral chemotherapy and should be considered part of
      a fail-safe process to improve safety.

PMID- 21084324
TI  - Exploration of health dimensions to be included in multi-attribute health-utility
      assessment.
AB  - OBJECTIVE: Measurement of health utility is important for quality improvement,
      but instruments vary in their content. Multi-attribute health utility measures
      typically assess a small number of health problems, e.g. the EuroQoL EQ-5D
      questionnaire explores five dimensions of health. We aimed to examine whether a
      small number of dimensions explains a sufficient amount of variance in self
      perceived health, and what can be gained from adding additional dimensions.
      DESIGN: Cross-sectional mail survey that explored health utility and self
      perceived health. SETTING: General resident population of French-speaking
      Switzerland. PARTICIPANTS: Non-institutionalized adults. MAIN OUTCOME MEASURES:
      EQ-5D (which measures mobility, self-care, usual activities, pain/discomfort,
      anxiety/depression and a visual analogue health scale between 0 and 100 (VAS)). A
      subsample rated five additional health dimensions (sleep, memory/concentration,
      energy/fatigue, sight/hearing, contacts with others). RESULTS: In total, 349
      adults returned the extended 10-item questionnaire. All added items were strongly
      and significantly associated with the VAS for perceived health. The proportion of
      variance explained (R(2)) in the VAS was 0.47 for the original EQ-5D items
      (adjusted for attenuation: 0.65), 0.47 for the new items (adjusted for
      attenuation: 0.65) and 0.56 for the 10 items together (adjusted for attenuation:
      0.78). Forty-four percent of the respondents who had a perfect health utility on
      the EQ-5D reported at least one problem in the new health dimensions. CONCLUSION:
      Self-perceived health among the general public is influenced by more health
      dimensions than are typically measured in a multi-attribute health-utility
      instrument.

PMID- 21084325
TI  - Sex differences in the relationship between bone mineral density and tibial
      cartilage volume.
AB  - OBJECTIVE: Although there is a well-established sex difference in the prevalence
      and severity of OA, the mechanism for this is not clear. The aim of this study
      was to examine the potential role of BMD and BMC in explaining gender differences
      in knee cartilage volume. METHODS: A total of 153 subjects aged 25-60 years, 81%
      female, were recruited. MRI was performed of the dominant knee. Cartilage volume
      was measured using validated methods. Total body BMD and content was measured
      using DXA. RESULTS: Total body BMC and BMD was significantly associated with
      medial cartilage volume in both sexes. However, the associations were stronger in
      men for BMC (B = 0.52; 95% CI 0.21, 0.83; P for difference = 0.001) and BMD (B =
      2242; 95% CI 443, 4041; P for difference = 0.05). Similar results were obtained
      in the lateral tibial compartment. No significant association was obtained
      between total body BMD and BMC and patella cartilage volume in either men or
      women. CONCLUSIONS: In this relatively healthy population, we found a positive
      relationship between total body BMD and BMC and tibial cartilage volume in the
      medial and lateral compartments. These relationships were stronger in men than
      women. Thus, the results of this study may provide some insight into the sex
      differences in knee cartilage volume, which may in turn facilitate our
      understanding of the pathogenesis of OA.

PMID- 21084326
TI  - Ten years with biologics: to whom do data on effectiveness and safety apply?
AB  - OBJECTIVES: During the past decade, the position of biologics in the therapeutic
      armamentarium, the number of approved indications and the number of available
      biologics have changed. Available data on (long-term) safety might thus pertain
      to patient populations not comparable with contemporary patients. The aim of this
      study was to assess the extent to which contemporary patients who start or switch
      biologic therapies are comparable with those patients who gave rise to the
      currently available data on effectiveness and safety. METHODS: We identified all
      adult patients with RA (n=9612), PsA (n=1417) and other SpA (n=1652) initiating a
      first biologic therapy between 1 January 1999 and 31 December 2008, registered in
      the Swedish Biologics Register (ARTIS), including information on demographics,
      disease characteristics and 1-year risk of first-line treatment discontinuation.
      RESULTS: Over calendar time, measures of disease activity at start declined
      substantially for all indications, and diminished between first-, second- and
      third-line therapy starts. One-year risks of first-line therapy discontinuation
      increased. Switchers to anti-TNF and non-TNF biologics had different
      comorbidities. Despite <50% drug retention at 5 years, most patients remained
      exposed to some biologic. CONCLUSIONS: The trends in baseline characteristics and
      drug retention underscores that any effects of biologics, including comparison
      between different biologics, must be interpreted in light of the characteristics
      of the population treated. The observed differences further call for continued
      vigilance to properly evaluate the safety profiles of biologic treatments as they
      are currently used. Exposure to multiple biologics presents a challenge for
      attribution of long-term effects.

PMID- 21084327
TI  - Risk of lung cancer associated with quantitative beryllium exposure metrics
      within an occupational cohort.
AB  - OBJECTIVES: Beryllium has been identified as a human carcinogen on the basis of
      animal and epidemiological studies. The authors recently reported updated
      associations between lung cancer and beryllium exposure in a large, pooled
      occupational cohort. The authors conducted the present study to evaluate the
      shape of exposure-response associations between different exposure metrics and
      lung cancer in this cohort, considering potential confounders (race, plant,
      professional and short-term work status, and exposure to other lung carcinogens).
      METHODS: The authors conducted Cox proportional hazards regression analyses of
      lung cancer risk with cumulative, mean and maximum 'daily weighted average' (DWA)
      exposure among 5436 workers, using age-based risk sets. Different exposure
      response curves were fitted to the exposure metrics, including categorical,
      power, restricted cubic spline and piecewise log-linear fits. RESULTS: The
      authors found significant positive associations between lung cancer and mean (p <
      0.0001) and maximum (p < 0.0001) exposure, adjusting for age, birth cohort and
      plant, and for cumulative (p = 0.0017) beryllium exposure, adjusting for these
      factors plus short-term work status and exposure to asbestos. The best-fitting
      models were generally categorical or piecewise log-linear, with the steepest
      increase in lung cancer risk between 0 and 10 MUg/m(3) for both mean and maximum
      DWA exposure and between 0 and 200 MUg/m(3)-days for cumulative DWA exposure. The
      estimated mean DWA beryllium exposure associated with 10(-3) excess lifetime risk
      based on the piecewise log-linear model is 0.033 MUg/m(3). CONCLUSION: This study
      provides evidence that lung cancer risk is elevated at levels near the current US
      Occupational Safety and Health Administration beryllium exposure limit of 2.0
      MUg/m(3) DWA for workers.

PMID- 21084329
TI  - Occupational exposure control: the problem of quantities in radiation protection.
AB  - The paper explores the quantities and units used in radiation protection with
      special emphasis on their applications in occupational exposure control. An
      overview of the current situation reveals that there seem to be too many
      different quantities associated with the same unit. Some of these quantities are
      defined in a quite complicated manner and, therefore, may cause some confusion in
      their interpretation and practical use in the field. Some suggestions towards the
      simplification of the present system are also proposed.

PMID- 21084328
TI  - Medication use in relation to noise from aircraft and road traffic in six
      European countries: results of the HYENA study.
AB  - OBJECTIVES: Studies on the health effects of aircraft and road traffic noise
      exposure suggest excess risks of hypertension, cardiovascular disease and the use
      of sedatives and hypnotics. Our aim was to assess the use of medication in
      relation to noise from aircraft and road traffic. METHODS: This cross-sectional
      study measured the use of prescribed antihypertensives, antacids, anxiolytics,
      hypnotics, antidepressants and antasthmatics in 4,861 persons living near seven
      airports in six European countries (UK, Germany, the Netherlands, Sweden, Italy,
      and Greece). Exposure was assessed using models with 1 dB resolution (5 dB for UK
      road traffic noise) and spatial resolution of 250*250 m for aircraft and 10*10 m
      for road traffic noise. Data were analysed using multilevel logistic regression,
      adjusting for potential confounders. RESULTS: We found marked differences between
      countries in the effect of aircraft noise on antihypertensive use; for night-time
      aircraft noise, a 10 dB increase in exposure was associated with ORs of 1.34 (95%
      CI 1.14 to 1.57) for the UK and 1.19 (1.02 to 1.38) for the Netherlands but no
      significant associations were found for other countries. For day-time aircraft
      noise, excess risks were found for the UK (OR 1.35; CI: 1.13 to 1.60) but a risk
      deficit for Italy (OR 0.82; CI: 0.71 to 0.96). There was an excess risk of taking
      anxiolytic medication in relation to aircraft noise (OR 1.28; CI: 1.04 to 1.57
      for daytime and OR 1.27; CI: 1.01 to 1.59 for night-time) which held across
      countries. We also found an association between exposure to 24hr road traffic
      noise and the use of antacids by men (OR 1.39; CI 1.11 to 1.74). CONCLUSION: Our
      results suggest an effect of aircraft noise on the use of antihypertensive
      medication, but this effect did not hold for all countries. Results were more
      consistent across countries for the increased use of anxiolytics in relation to
      aircraft noise.

PMID- 21084330
TI  - Accreditation of testing laboratories in dosimetry: the use of a flexible scope
      at the Competent Incorporation Measuring Body Julich.
AB  - The accreditation of the Competent Incorporation Measuring Body at Julich
      includes incorporation monitoring by means of direct measurements of the body
      activity as well as by means of indirect determination of the body activity by
      radiochemical analysis of excreta samples. In both testing areas, it proved to be
      very useful to have a flexible scope. In particular, the associated freedom in
      choosing testing procedures supports the continual improvement process of the
      laboratory. The modification of existing methods as well as the development and
      introduction of new procedures makes an immediate reaction to changed
      requirements feasible. At Julich the use made out of the flexible scope included,
      e.g. the introduction of mathematical calibration in whole-body counting and the
      automation of sample preparation in radiochemical analysis. Advantages of the new
      procedures and modified methods include on the one hand the reduction of
      processing times, downtimes and hazard potentials on the other hand enhanced
      detection limits and improved cost-efficiency. In the result, it can be
      recommended to other qualified testing laboratories to go for a flexible scope.

PMID- 21084331
TI  - Monte Carlo evaluation of DNA fragmentation spectra induced by different
      radiation qualities.
AB  - The PARTRAC code has been developed constantly in the last several years. It is a
      Monte Carlo code based on an event-by-event description of the interactions
      taking place between the ionising radiation and liquid water, and in the present
      version simulates the transport of photons, electrons, protons, helium and
      heavier ions. This is combined with an atom-by-atom representation of the
      biological target, i.e. the DNA target model of a diploid human fibroblast in its
      interphase (genome of 6 Gigabase pairs). DNA damage is produced by the events of
      energy depositions, either directly, if they occur in the volume occupied by the
      sugar-phosphate backbone, or indirectly, if this volume is reached by radiation
      induced radicals. This requires the determination of the probabilities of
      occurrence of DNA damage. Experimental data are essential for this determination.
      However, after the adjustment of the relevant parameters through the comparison
      of the simulation data with the DNA fragmentation induced by photon irradiation,
      the code has been used without further parameter adjustments, and the comparison
      with the fragmentation induced by charged particle beams has validated the code.
      In this paper, the results obtained for the DNA fragmentation induced by gamma
      rays and by charged particle beams of various LET are shown, with a particular
      attention to the production of very small fragments that are not detected in
      experiments.

PMID- 21084332
TI  - Uncertainty attributed to signal averaging in a single averaged alanine EPR
      spectrum for low-dose applications.
AB  - During the past 50 y alanine has been considered a reference dosimetry system
      using electron paramagnetic resonance (EPR), especially for the high doses
      associated with radiation processing. Extension of alanine/EPR system
      applications to the lower doses associated with radiation therapy and/or
      radiation protection is limited by the ability to extract the dosimetric signal
      with minimum associated noise. The signal-averaging technique is one of the
      common numerical methods used for enhancing the signal-to-noise ratio, through
      which the accumulated repetitive scans causes the reduction of noise due to its
      random behaviour and the signal growth due to its persistence. However, the use
      of signal averaging is usually associated with some uncertainty, which is not
      usually considered. In this work, there is a clarification of the importance of
      the evaluation of uncertainty associated to the single averaged alanine spectrum.

PMID- 21084333
TI  - Learning to understand others' actions.
AB  - Despite nearly two decades of research on mirror neurons, there is still much
      debate about what they do. The most enduring hypothesis is that they enable
      'action understanding'. However, recent critical reviews have failed to find
      compelling evidence in favour of this view. Instead, these authors argue that
      mirror neurons are produced by associative learning and therefore that they
      cannot contribute to action understanding. The present opinion piece suggests
      that this argument is flawed. We argue that mirror neurons may both develop
      through associative learning and contribute to inferences about the actions of
      others.

PMID- 21084334
TI  - Specific, non-nutritional association between an ascomycete fungus and Allomerus
      plant-ants.
AB  - Ant-fungus associations are well known from attine ants, whose nutrition is based
      on a symbiosis with basidiomycete fungi. Otherwise, only a few non-nutritional
      ant-fungus associations have been recorded to date. Here we focus on one of these
      associations involving Allomerus plant-ants that build galleried structures on
      their myrmecophytic hosts in order to ambush prey. We show that this association
      is not opportunistic because the ants select from a monophyletic group of closely
      related fungal haplotypes of an ascomycete species from the order Chaetothyriales
      that consistently grows on and has been isolated from the galleries. Both the
      ants' behaviour and an analysis of the genetic population structure of the ants
      and the fungus argue for host specificity in this interaction. The ants'
      behaviour reveals a major investment in manipulating, growing and cleaning the
      fungus. A molecular analysis of the fungus demonstrates the widespread occurrence
      of one haplotype and many other haplotypes with a lower occurrence, as well as
      significant variation in the presence of these fungal haplotypes between areas
      and ant species. Altogether, these results suggest that such an interaction might
      represent an as-yet undescribed type of specific association between ants and
      fungus in which the ants cultivate fungal mycelia to strengthen their hunting
      galleries.

PMID- 21084335
TI  - Differential outcomes of unilateral interferences at birth.
AB  - Behavioural modifications, including modifications of emotional reactivity, can
      occur following early experience such as handling (manual rubbing). Here, we
      investigated the effects of unilateral tactile stimulation at an early stage on
      emotional reactions later on. We handled newborn foals intensively on one side of
      their body. This early unilateral tactile experience had medium-term effects: the
      reactions of foals to a human approach, when they were 10 days old, differed
      according to the side stimulated at birth. Fewer right-handled foals accepted
      contact with humans, they delayed first contact longer and they evaded
      approaching humans sooner than did non-handled and left-handled foals. These
      results raise questions concerning the organization of neonatal care in animals
      and humans.

PMID- 21084336
TI  - Frugivores and seed dispersal: mechanisms and consequences for biodiversity of a
      key ecological interaction.
AB  - The 5th Symposium on Frugivores and Seed Dispersal, held in Montpellier (France),
      13-18 June 2010, brought together more than 220 researchers exemplifying a wide
      diversity of approaches to the study of frugivory and dispersal of seeds.
      Following Ted Fleming and Alejandro Estrada's initiative in 1985, this event was
      a celebration of the 25th anniversary of the first meeting in Veracruz, Mexico.
      Frugivory and seed dispersal are active research areas that have diversified in
      multiple directions since 1985 to include evolution (e.g. phylogenetic diversity
      and dispersal adaptations), physiology (e.g. sensory cues and digestion),
      landscape ecology (movement patterns), molecular ecology (e.g. gene flow, genetic
      diversity and structure), community ecology (e.g. mutualistic interaction
      networks) and conservation biology (effects of hunting, fragmentation, invasion
      and extinction), among others. This meeting provided an opportunity to assess
      conceptual and methodological progress, to present ever more sophisticated
      insights into frugivory in animals and dispersal patterns in plants, and to
      report the advances made in examining the mechanisms and consequences of seed
      dispersal for plants and frugivores.

PMID- 21084337
TI  - Fish mucous cocoons: the 'mosquito nets' of the sea.
AB  - Mucus performs numerous protective functions in vertebrates, and in fishes may
      defend them against harmful organisms, although often the evidence is
      contradictory. The function of the mucous cocoons that many parrotfishes and
      wrasses sleep in, while long used as a classical example of antipredator
      behaviour, remains unresolved. Ectoparasitic gnathiid isopods (Gnathiidae), which
      feed on the blood of fish, are removed by cleaner fish during the day; however,
      it is unclear how parrotfish and wrasse avoid gnathiid attacks at night. To test
      the novel hypothesis that mucous cocoons protect against gnathiids, we exposed
      the coral reef parrotfish Chlorurus sordidus (Scaridae) with and without cocoons
      to gnathiids overnight and measured the energetic content of cocoons. Fish
      without mucous cocoons were attacked more by gnathiids than fish with cocoons.
      The energetic content of mucous cocoons was estimated as 2.5 per cent of the
      fish's daily energy budget fish. Therefore, mucous cocoons protected against
      attacks by gnathiids, acting like mosquito nets in humans, a function of cocoons
      and an efficient physiological adaptation for preventing parasite infestation
      that is not used by any other animal.

PMID- 21084338
TI  - Nonlinear speech analysis algorithms mapped to a standard metric achieve
      clinically useful quantification of average Parkinson's disease symptom severity.
AB  - The standard reference clinical score quantifying average Parkinson's disease
      (PD) symptom severity is the Unified Parkinson's Disease Rating Scale (UPDRS). At
      present, UPDRS is determined by the subjective clinical evaluation of the
      patient's ability to adequately cope with a range of tasks. In this study, we
      extend recent findings that UPDRS can be objectively assessed to clinically
      useful accuracy using simple, self-administered speech tests, without requiring
      the patient's physical presence in the clinic. We apply a wide range of known
      speech signal processing algorithms to a large database (approx. 6000 recordings
      from 42 PD patients, recruited to a six-month, multi-centre trial) and propose a
      number of novel, nonlinear signal processing algorithms which reveal pathological
      characteristics in PD more accurately than existing approaches. Robust feature
      selection algorithms select the optimal subset of these algorithms, which is fed
      into non-parametric regression and classification algorithms, mapping the signal
      processing algorithm outputs to UPDRS. We demonstrate rapid, accurate replication
      of the UPDRS assessment with clinically useful accuracy (about 2 UPDRS points
      difference from the clinicians' estimates, p<0.001). This study supports the
      viability of frequent, remote, cost-effective, objective, accurate UPDRS
      telemonitoring based on self-administered speech tests. This technology could
      facilitate large-scale clinical trials into novel PD treatments.

PMID- 21084339
TI  - Parameterizing state-space models for infectious disease dynamics by generalized
      profiling: measles in Ontario.
AB  - Parameter estimation for infectious disease models is important for basic
      understanding (e.g. to identify major transmission pathways), for forecasting
      emerging epidemics, and for designing control measures. Differential equation
      models are often used, but statistical inference for differential equations
      suffers from numerical challenges and poor agreement between observational data
      and deterministic models. Accounting for these departures via stochastic model
      terms requires full specification of the probabilistic dynamics, and
      computationally demanding estimation methods. Here, we demonstrate the utility of
      an alternative approach, generalized profiling, which provides robustness to
      violations of a deterministic model without needing to specify a complete
      probabilistic model. We introduce novel means for estimating the robustness
      parameters and for statistical inference in this framework. The methods are
      applied to a model for pre-vaccination measles incidence in Ontario, and we
      demonstrate the statistical validity of our inference through extensive
      simulation. The results confirm that school term versus summer drives seasonality
      of transmission, but we find no effects of short school breaks and the estimated
      basic reproductive ratio (0) greatly exceeds previous estimates. The approach
      applies naturally to any system for which candidate differential equations are
      available, and avoids many challenges that have limited Monte Carlo inference for
      state-space models.

PMID- 21084340
TI  - Indoor residual spray and insecticide-treated bednets for malaria control:
      theoretical synergisms and antagonisms.
AB  - Indoor residual spray (IRS) of insecticides and insecticide-treated bednets
      (ITNs) are the two most important malaria vector control tools in the tropical
      world. Application of both tools in the same locations is being implemented for
      malaria control in endemic and epidemic Africa. The two tools are assumed to have
      synergistic benefits in reducing malaria transmission because they both act at
      multiple stages of the transmission cycle. However, this assumption has not been
      rigorously examined, empirically or theoretically. Using mathematical modelling,
      we obtained the conditions for which a combination strategy can be expected to
      improve upon single control tools. Specifically, spraying of
      dichlorodiphenyltrichloroethane (DDT) in all houses where residents are not using
      ITNs can reduce transmission of malaria (R(0)) by up to 10 times more than the
      reduction achieved through ITNs alone. Importantly, however, we also show how
      antagonism between control tools can arise via interference of their modes of
      action. Repellent IRS reduces the likelihood that ITNs are contacted within
      sprayed houses and ITNs reduce the rate at which blood-fed mosquitoes rest on
      sprayed walls. For example, 80 per cent coverage of ITNs and DDT used together at
      the household level resulted in an R(0) of 11.1 when compared with an R(0) of 0.1
      achieved with 80 per cent ITN coverage without DDT. While this undesired effect
      can be avoided using low-repellence pyrethroid chemicals for IRS, the extent of
      the potential benefits is also attenuated. We discuss the impact that this result
      will likely have on future efforts in malaria control combination strategy.

PMID- 21084341
TI  - The statistical mechanics of a polygenic character under stabilizing selection,
      mutation and drift.
AB  - By exploiting an analogy between population genetics and statistical mechanics,
      we study the evolution of a polygenic trait under stabilizing selection, mutation
      and genetic drift. This requires us to track only four macroscopic variables,
      instead of the distribution of all the allele frequencies that influence the
      trait. These macroscopic variables are the expectations of: the trait mean and
      its square, the genetic variance, and of a measure of heterozygosity, and are
      derived from a generating function that is in turn derived by maximizing an
      entropy measure. These four macroscopics are enough to accurately describe the
      dynamics of the trait mean and of its genetic variance (and in principle of any
      other quantity). Unlike previous approaches that were based on an infinite series
      of moments or cumulants, which had to be truncated arbitrarily, our calculations
      provide a well-defined approximation procedure. We apply the framework to abrupt
      and gradual changes in the optimum, as well as to changes in the strength of
      stabilizing selection. Our approximations are surprisingly accurate, even for
      systems with as few as five loci. We find that when the effects of drift are
      included, the expected genetic variance is hardly altered by directional
      selection, even though it fluctuates in any particular instance. We also find
      hysteresis, showing that even after averaging over the microscopic variables, the
      macroscopic trajectories retain a memory of the underlying genetic states.

PMID- 21084342
TI  - The importance of structured noise in the generation of self-organizing tissue
      patterns through contact-mediated cell-cell signalling.
AB  - Lateral inhibition provides the basis for a self-organizing patterning system in
      which distinct cell states emerge from an otherwise uniform field of cells. The
      development of the microchaete bristle pattern on the notum of the fruitfly,
      Drosophila melanogaster, has long served as a popular model of this process. We
      recently showed that this bristle pattern depends upon a population of dynamic,
      basal actin-based filopodia, which span multiple cell diameters. These
      protrusions establish transient signalling contacts between non-neighbouring
      cells, generating a type of structured noise that helps to yield a well-ordered
      and spaced pattern of bristles. Here, we develop a general model of protrusion
      based patterning to analyse the role of noise in this process. Using a simple
      asynchronous cellular automata rule-based model we show that this type of
      structured noise drives the gradual refinement of lateral inhibition-mediated
      patterning, as the system moves towards a stable configuration in which cells
      expressing the inhibitory signal are near-optimally packed. By analysing the
      effects of introducing thresholds required for signal detection in this model of
      lateral inhibition, our study shows how filopodia-mediated cell-cell
      communication can generate complex patterns of spots and stripes, which, in the
      presence of signalling noise, align themselves across a patterning field. Thus,
      intermittent protrusion-based signalling has the potential to yield robust self
      organizing tissue-wide patterns without the need to invoke diffusion-mediated
      signalling.

PMID- 21084343
TI  - Retrieval of phytoplankton size from bio-optical measurements: theory and
      applications.
AB  - The absorption coefficient of a substance distributed as discrete particles in
      suspension is less than that of the same material dissolved uniformly in a medium
      a phenomenon commonly referred to as the flattening effect. The decrease in the
      absorption coefficient owing to flattening effect depends on the concentration of
      the absorbing pigment inside the particle, the specific absorption coefficient of
      the pigment within the particle, and on the diameter of the particle, if the
      particles are assumed to be spherical. For phytoplankton cells in the ocean, with
      diameters ranging from less than 1 um to more than 100 um, the flattening effect
      is variable, and sometimes pronounced, as has been well documented in the
      literature. Here, we demonstrate how the in vivo absorption coefficient of
      phytoplankton cells per unit concentration of its major pigment, chlorophyll a,
      can be used to determine the average cell size of the phytoplankton population.
      Sensitivity analyses are carried out to evaluate the errors in the estimated
      diameter owing to potential errors in the model assumptions. Cell sizes computed
      for field samples using the model are compared qualitatively with indirect
      estimates of size classes derived from high performance liquid chromatography
      data. Also, the results are compared quantitatively against measurements of cell
      size in laboratory cultures. The method developed is easy-to-apply as an
      operational tool for in situ observations, and has the potential for application
      to remote sensing of ocean colour data.

PMID- 21084344
TI  - Electroporation and lysis of marine microalga Karenia brevis for RNA extraction
      and amplification.
AB  - We describe here a simple device for dielectrophoretic concentration of marine
      microalga Karenia brevis non-motile cells, followed by electric field-mediated
      lysis for RNA extraction. The lysate was purified using magnetic beads and pure
      RNA extracted. RNA quality was assessed off-chip by nucleic acid sequence-based
      amplification and the optimum conditions for lysis were determined. This
      procedure will form part of an integrated microfluidic system that is being
      developed with sub-systems for performing cell concentration and lysis, RNA
      extraction/purification and real-time quantitative RNA detection. The integrated
      system and its components could be used for a large range of applications
      including in situ harmful algal bloom detection, transcriptomics and point-of
      care diagnostics.

PMID- 21084345
TI  - Escherichia coli O157 infection on Scottish cattle farms: dynamics and control.
AB  - In this study, we parametrize a stochastic individual-based model of the
      transmission dynamics of Escherichia coli O157 infection among Scottish cattle
      farms and use the model to predict the impacts of both targeted and non-targeted
      interventions. We first generate distributions of model parameter estimates using
      Markov chain Monte Carlo methods. Despite considerable uncertainty in parameter
      values, each set of parameter values within the 95th percentile range implies a
      fairly similar impact of interventions. Interventions that reduce the
      transmission coefficient and/or increase the recovery rate of infected farms
      (e.g. via vaccination and biosecurity) are much more effective in reducing the
      level of infection than reducing cattle movement rates, which improves
      effectiveness only when the overall control effort is small. Targeted
      interventions based on farm-level risk factors are more efficient than non
      targeted interventions. Herd size is a major determinant of risk of infection,
      and our simulations confirmed that targeting interventions at farms with the
      largest herds is almost as effective as targeting based on overall risk. However,
      because of the striking characteristic that the infection force depends weakly on
      the number of infected farms, no interventions that are less than 100 per cent
      effective can eradicate E. coli O157 infection from Scottish cattle farms,
      implying that eliminating the disease is impractical.

PMID- 21084346
TI  - Enhanced resistance to fungal pathogens in transgenic Populus tomentosa Carr. by
      overexpression of an nsLTP-like antimicrobial protein gene from motherwort
      (Leonurus japonicus).
AB  - The antimicrobial protein gene LJAMP2 is a plant non-specific lipid transfer
      protein from motherwort (Leonurus japonicus). In this study, it was introduced
      into Chinese white poplar (Populus tomentosa Carr.) via Agrobacterium-mediated
      transformation with neomycin phosphotransferase II gene conferring kanamycin
      resistance as selectable marker. A total of 16 poplar lines were obtained, and
      polymerase chain reaction (PCR) analysis established the stable integration of
      transgenes in the plant genome. Reverse transcription-PCR detected LJAMP2
      expression in transgenic plants. Resistance to fungal pathogens Alternaria
      alternata (Fr.) Keissler and Colletotrichum gloeosporioides (Penz.) of transgenic
      poplar lines was tested. In vitro inhibitory activity against the fungal
      pathogens was evident from the crude leaf extracts from the transformants. In
      vivo assays showed that, after infection with both A. alternata (Fr.) Keissler
      and C. gloeosporioides (Penz.), there was a significant reduction in disease
      symptoms in transgenic poplar plants compared with the control. These results
      suggest that constitutive expression of the LJAMP2 gene from motherwort can be
      exploited to improve resistance to fungal pathogens in poplar.

PMID- 21084347
TI  - Hunting at the highway: traffic noise reduces foraging efficiency in acoustic
      predators.
AB  - Noise pollution from human traffic networks and industrial activity impacts vast
      areas of our planet. While anthropogenic noise effects on animal communication
      are well documented, we have very limited understanding of noise impact on more
      complex ecosystem processes, such as predator-prey interactions, albeit urgently
      needed to devise mitigation measures. Here, we show that traffic noise decreases
      the foraging efficiency of an acoustic predator, the greater mouse-eared bat
      (Myotis myotis). These bats feed on large, ground-running arthropods that they
      find by listening to their faint rustling sounds. We measured the bats' foraging
      performance on a continuous scale of acoustically simulated highway distances in
      a behavioural experiment, designed to rule out confounding factors such as
      general noise avoidance. Successful foraging bouts decreased and search time
      drastically increased with proximity to the highway. At 7.5 m to the road, search
      time was increased by a factor of five. From this increase, we predict a 25-fold
      decrease in surveyed ground area and thus in foraging efficiency for a wild bat.
      As most of the bats' prey are predators themselves, the noise impact on the bats'
      foraging performance will have complex effects on the food web and ultimately on
      the ecosystem stability. Similar scenarios apply to other ecologically important
      and highly protected acoustic predators, e.g. owls. Our study provides the
      empirical basis for quantitative predictions of anthropogenic noise impacts on
      ecosystem processes. It highlights that an understanding of the effects of noise
      emissions and other forms of 'sensory pollution' are crucially important for the
      assessment of environmental impact of human activities.

PMID- 21084348
TI  - From the first intention movement to the last joiner: macaques combine mimetic
      rules to optimize their collective decisions.
AB  - Mechanisms related to collective decision making have recently been found in
      almost all animal reigns from amoebae to worms, insects and vertebrates,
      including human beings. Decision-making mechanisms related to collective
      movements-including pre-departure and joining-have already been studied at
      different steps of the movement process, but these studies were always carried
      out separately. We therefore have no understanding of how these different
      processes are related when they underlie the same collective decision-making
      event. Here, we consider the whole departure process of two groups of Tonkean
      macaques (Macaca tonkeana), using a stochastic model. When several exclusive
      choices are proposed, macaques vote and choose the majority. Individuals then
      join the movement according to a mimetism based on affiliative relationships. The
      pre-departure quorum and the joining mimetic mechanism are probably linked, but
      we have not yet identified which transition mechanism is used. This study shows
      that decision-making related to macaque group movements is governed by a quorum
      rule combined with a selective mimetism at departure. This is the first time that
      transition mechanisms have been described in mammals, which consequently helps
      understand how a voting process leads to social amplification. Our study also
      provides the first complete proof that there is continuity in the decision-making
      processes underlying collective movements in mammals from the first intention
      movement right through to the last joiner.

PMID- 21084349
TI  - Environmental, pharmacological and genetic influences on the spread of drug
      resistant malaria.
AB  - Plasmodium falciparum malaria is subject to artificial selection from
      antimalarial drugs that select for drug-resistant parasites. We describe and
      apply a flexible new approach to investigate how epistasis, inbreeding, selection
      heterogeneity and multiple simultaneous drug deployments interact to influence
      the spread of drug-resistant malaria. This framework recognizes that different
      human 'environments' within which treatment may occur (such as semi- and non
      immune humans taking full or partial drug courses) influence the genetic
      interactions between parasite loci involved in resistance. Our model provides an
      explanation for how the rate of spread varies according to different malaria
      transmission intensities, why resistance might stabilize at intermediate
      frequencies and also identifies several factors that influence the decline of
      resistance after a drug is removed. Results suggest that studies based on
      clinical outcomes might overestimate the spread of resistant parasites,
      especially in high-transmission areas. We show that when transmission decreases,
      prevalence might decrease without a corresponding change in frequency of
      resistance and that this relationship is heavily influenced by the extent of
      linkage disequilibrium between loci. This has important consequences on the
      interpretation of data from areas where control is being successful and suggests
      that reducing transmission might have less impact on the spread of resistance
      than previously expected.

PMID- 21084350
TI  - Phenotypic convergence along a gradient of predation risk.
AB  - A long-standing question in ecology is whether phenotypic plasticity, rather than
      selection per se, is responsible for phenotypic variation among populations.
      Plasticity can increase or decrease variation, but most previous studies have
      been limited to single populations, single traits and a small number of
      environments assessed using univariate reaction norms. Here, examining two
      genetically distinct populations of Daphnia pulex with different predation
      histories, we quantified predator-induced plasticity among 11 traits along a fine
      scale gradient of predation risk by a predator (Chaoborus) common to both
      populations. We test the hypothesis that plasticity can be responsible for
      convergence in phenotypes among different populations by experimentally
      characterizing multivariate reaction norms with phenotypic trajectory analysis
      (PTA). Univariate analyses showed that all genotypes increased age and size at
      maturity, and invested in defensive spikes (neckteeth), but failed to
      quantitatively describe whole-organism response. In contrast, PTA quantified and
      qualified the phenotypic strategy the organism mobilized against the selection
      pressure. We demonstrate, at the whole-organism level, that the two populations
      occupy different areas of phenotypic space in the absence of predation but
      converge in phenotypic space as predation threat increases.

PMID- 21084351
TI  - Global protected area impacts.
AB  - Protected areas (PAs) dominate conservation efforts. They will probably play a
      role in future climate policies too, as global payments may reward local
      reductions of loss of natural land cover. We estimate the impact of PAs on
      natural land cover within each of 147 countries by comparing outcomes inside PAs
      with outcomes outside. We use 'matching' (or 'apples to apples') for land
      characteristics to control for the fact that PAs very often are non-randomly
      distributed across their national landscapes. Protection tends towards land that,
      if unprotected, is less likely than average to be cleared. For 75 per cent of
      countries, we find protection does reduce conversion of natural land cover.
      However, for approximately 80 per cent of countries, our global results also
      confirm (following smaller-scale studies) that controlling for land
      characteristics reduces estimated impact by half or more. This shows the
      importance of controlling for at least a few key land characteristics. Further,
      we show that impacts vary considerably within a country (i.e. across a
      landscape): protection achieves less on lands far from roads, far from cities and
      on steeper slopes. Thus, while planners are, of course, constrained by other
      conservation priorities and costs, they could target higher impacts to earn more
      global payments for reduced deforestation.

PMID- 21084352
TI  - Antipodean white sharks on a Mediterranean walkabout? Historical dispersal leads
      to genetic discontinuity and an endangered anomalous population.
AB  - The provenance of white sharks (Carcharodon carcharias) in the Mediterranean is
      both a conundrum and an important conservation issue. Considering this species's
      propensity for natal philopatry, any evidence that the Mediterranean stock has
      little or no contemporary immigration from the Atlantic would suggest that it is
      extraordinarily vulnerable. To address this issue we sequenced the mitochondrial
      control region of four rare Mediterranean white sharks. Unexpectedly, the
      juvenile sequences were identical although collected at different locations and
      times, showing little genetic differentiation from Indo-Pacific lineages, but
      strong separation from geographically closer Atlantic/western Indian Ocean
      haplotypes. Historical long-distance dispersal (probably a consequence of
      navigational error during past climatic oscillations) and potential founder
      effects are invoked to explain the anomalous relationships of this isolated
      'sink' population, highlighting the present vulnerability of its nursery grounds.

PMID- 21084353
TI  - Is consent for hip fracture surgery for older people adequate? The case for pre
      printed consent forms.
AB  - OJECTIVES: Low energy hip fractures are one of the greatest causes of morbidity
      and mortality in orthopaedics. This study aims to evaluate written consent forms
      with respect to basic standards as set out in the Good Practice in Consent
      Initiative. In particular the stated risks and benefits of each procedure were
      assessed. METHODS: 100 consecutive consent forms were reviewed prospectively. The
      stated procedure, side and complications were recorded. Appropriate signature and
      legibility was assessed. 13 consultant orthopaedic surgeons were surveyed to
      identify what risks and benefits they thought should be stated. RESULTS: Of 100
      consent forms, 31 were for patients who are unable to consent. All 100 consent
      forms were correctly filled in with patient details and signed. 98% were legible.
      All stated the side of the operation. The number of complications listed per form
      ranged from 4 to 11. Infection, bleeding and thromboembolic complications were
      stated in the majority of consent forms. In total, 30 different complications
      were recorded; some were only stated once. DISCUSSION AND CONCLUSIONS: This work
      suggests consent forms are completed well with respect to patient identifiers,
      legibility and procedure. The variability of complications stated is vast. We
      suggest standard pre-printed consent forms containing risks and benefits should
      be used as this may improve standards of informed consent. This has also been
      recently supported by the British Orthopaedic Association.

PMID- 21084354
TI  - Ethical dilemmas in medical humanitarian practice: cases for reflection from
      Medecins Sans Frontieres.
AB  - Medecins Sans Frontieres (MSF) is an independent medical humanitarian
      organisation working in over 70 countries. It has provided medical assistance for
      over 35&emsp14;years to populations vulnerable through conflict, disease and
      inadequate health systems. Medical ethics define the starting point of the
      relationship between medical staff and patients. The ethics of humanitarian
      interventions and of research in conflict settings are much debated. However,
      less is known about the ethical dilemmas faced by medical humanitarian staff in
      their daily work. Ethical dilemmas can be intensified in humanitarian contexts by
      insecure environments, lack of optimum care, language barriers, potentially
      heightened power discrepancies between care providers and patients, differing
      cultural values and perceptions of patients, communities and medical staff. Time
      constraints, stressful conditions and lack of familiarity with ethical frameworks
      can prevent reflection on these dilemmas, as can frustration that such reflection
      does not necessarily provide instant solutions. Lack of reflection, however, can
      be distressing for medical practitioners and can reduce the quality of care.
      Ethical reflection has a central role in MSF, and the organisation uses ethical
      frameworks to help with clinical and programmatic decisions as well as in
      deliberations over operational research. We illustrate and discuss some real
      ethical dilemmas facing MSF teams. Only by sharing and seeking guidance can MSF
      and similar actors make more thoughtful and appropriate decisions. Our aim in
      sharing these cases is to invite discussion and dialogue in the wider medical
      community working in crisis, conflict or with severe resource limitations.

PMID- 21084355
TI  - The right to die in the minimally conscious state.
AB  - The right to die has for decades been recognised for persons in a vegetative
      state, but there remains controversy about ending life-sustaining medical
      treatment for persons in the minimally conscious state (MCS). The controversy is
      rooted in assumptions about the moral significance of consciousness, and the
      value of life for patients who are conscious and not terminally ill. This paper
      evaluates these assumptions in light of evidence that generates concerns about
      quality of life in the MCS. It is argued that surrogates should be permitted to
      make decisions to withdraw life-sustaining medical treatment from patients in the
      MCS.

PMID- 21084356
TI  - The moral primacy of the human being: a reply to Parker.
AB  - In a previous paper in the Journal of Medical Ethics, the authors argued that the
      research ethical principle stating that the individual shall have priority over
      science, found in many guidelines, is utterly unclear and because of this should
      be explicated or otherwise deleted. In a recent commentary, Parker argued that
      this leaves us defending a position that would allow totalitarian regimes to
      pursue glory at the expense of its citizens. The present response addresses this
      and similar accusations.

PMID- 21084357
TI  - Diaphragm paralysis due to pseudoaneurysm of internal mammary artery after
      pacemaker implantation.
AB  - A patient was admitted with pain in the left shoulder and neck 15 days after
      pacemaker implantation. A pseudoaneurysm of the left internal mammary artery was
      found and a transarterial coil embolization was performed.

PMID- 21084358
TI  - The prognostic value of treadmill exercise testing in very elderly patients:
      heart rate recovery as a predictor of mortality in octogenarians.
AB  - AIMS: Several treadmill exercise testing prognostic parameters have been
      identified in various populations. However, despite the widespread use of
      treadmill exercise testing, the prognostic value in very elderly patients has not
      been well characterized. The aim of this study was to assess the results of
      treadmill exercise testing in octogenarians, and to examine various parameters in
      order to identify a prognostic marker of mortality. METHODS AND RESULTS: This
      study included 97 consecutive octogenarians (age, 81.1 +/- 1.8 years; 66% male)
      who were referred for treadmill exercise testing. During the follow-up period
      (2.6 +/- 1.6 years), all-cause death occurred in 20 patients (21%). Univariate
      Cox proportional hazard regression analysis showed that abnormal heart rate
      recovery (HRR) (defined as a decreased heart rate of <= 18 beats per minute after
      peak exercise) [hazard ratio (HR), 2.82; 95% confidence interval (CI), 1.06-7.47;
      P = 0.037] and ischaemic ST-segment change (HR, 2.56; 95% CI, 1.01-6.46; P =
      0.047) were significantly associated with all-cause mortality. After adjusting
      for age and sex, multivariate Cox proportional hazard analysis showed that
      abnormal HRR was the only independent predictor of all-cause death (HR, 2.86; 95%
      CI, 1.01-8.11; P = 0.048). CONCLUSION: Attenuated HRR is a significant prognostic
      marker for all-cause death among octogenarians. The results may provide helpful
      support for risk stratification in clinical practice.

PMID- 21084359
TI  - Percutaneous extraction of cardiac pacemaker and implantable cardioverter
      defibrillator leads with evolution mechanical dilator sheath: a single-centre
      experience.
AB  - AIMS: The growing problem with endocardial lead infections and lead malfunctions
      has increased the interest in percutaneous lead removal technology. In this
      report, we present our initial experience in percutaneous lead extraction with a
      novel hand-powered sheath, the Evolution mechanical dilator sheath. METHODS AND
      RESULTS: During 13 months between June 2009 and July 2010, 41 leads in 23
      patients were removed. All of the extracted leads were >12 months old, and
      indications for extraction were based on the recommendations of the Heart Rhythm
      Society. The leads were removed by using the Evolution mechanical dilator sheath
      (Cook Medical) with the rotational cutting force only, without laser or
      radiofrequency energy. Indications for lead removal included cardiac device
      infection in 7 (30.4%) cases, lead malfunction in the 15 (65.2%) cases, and lead
      displacement in the remaining 1 case (4.4%). In 14 (60.9%) cases, the extracted
      device was a pacemaker, and implantable cardioverter defibrillators (ICD) in 9
      (39.1%) of them. Among 41 leads, 25 (60.9%) were right ventricular, 14 (34%) were
      atrial, and 2 (4.8%) were coronary sinus electrode. The median time from the
      preceding procedure was 74 months (25-180 months). Complete procedural success
      with Evolution system alone was achieved in 19 (82%) patients (35 leads). Four
      leads were completely removed with snaring and in two leads, partial success was
      achieved with a remaining ventricular tip smaller than 1.5 cm. Clinical success
      was 100%, and all of the patients discharged uneventfully without a major
      complication. CONCLUSIONS: Our experience confirms that the mechanical technique
      with Evolution system is an effective first-line method for chronically implanted
      pacemaker/ICD leads. Continued investigation is required to evaluate success and
      complication rates in comparison with other techniques.

PMID- 21084360
TI  - Investigation of pacemaker position, lead configuration, and sensitivity setting
      in pacemakers of 579 deceased patients.
AB  - AIMS: The position of the pacemaker (PM) system (right or left-sided, pectoral,
      or abdominal), the ventricular lead configuration (unipolar or bipolar), the
      programmed ventricular sensitivity setting (SS), and the ventricular sensitivity
      of the pulse generator (PG) against electromagnetic interference (EMI) are
      decisive parameters with respect to EMI behaviour of PGs. Three of these
      ventricular parameters were investigated in PM of 579 deceased patients. MATERIAL
      AND METHODS: We investigated PM function provided a regular stimulation pattern
      in 878 deceased PM patients before cremation. The PG was explanted and then
      measured in a bench test in the laboratory with respect to the programmed
      parameters. Further investigations were restricted to 579 patients with PGs
      implanted between 1998 and 2004. The following parameters were evaluated: (i)
      position of the PG, (ii) lead configuration, and (iii) programmed SS of the
      ventricular channel. SS was measured according to the European Pacemaker
      Standards. Out of 579 patients, 556 PMs were implanted pectorally, with 172 on
      the left side (30.9%) and 384 on the right side (69.1%). In 23 cases, the
      implantation site was unknown. Out of 579 PMs, 282 ventricular leads were
      unipolar (48.7%). Of the 297 bipolar leads (51.3%), 61 (20.5%) had a unipolar
      sensing function so that a total majority of 343 PM (59.2%) had unipolar sensing.
      The mean value of SS was 3.24 mV (range: 1.2-8.1 mV) for unipolar leads and 3.55
      mV (range: 1.05-10.9 mV) for bipolar ones. The PGs with unipolarized bipolar
      leads were even more sensitive at 3.0 mV. Of the 579 PM systems, 0.67% possessed
      a combination of parameters: left side, unipolar and with SS < 2 mV. CONCLUSIONS:
      The results seemed to be paradoxical in that unipolar sensitivity was more
      sensitive than bipolar sensitivity. Less than 0.67% of patients possessed a worst
      case PM system with respect to EMI: a unipolar, left-sided PG with a ventricular
      SS < 2 mV. This implies that ~2345 PM patients in Germany could be at risk. Out
      of the 61 PGs with unipolarized bipolar leads, 14 had never been programmed as
      they still possessed the shipping programming. Unipolar leads can be used with
      left-side implantation if the SS is 3 mV (median value of all leads in our study)
      or higher. This would largely improve the immunity of PGs to EMI in the future.
      This study also demonstrates that there is a need for educational measures.

PMID- 21084361
TI  - Catheter tip force required for mechanical perforation of porcine cardiac
      chambers.
AB  - AIMS: Catheter manipulation during ablation procedures can produce injury and
      tamponade. We evaluated the mechanical forces required to perforate a porcine
      heart with an ablation catheter. METHODS AND RESULTS: A 7 Fr, 3.5 mm irrigated
      radiofrequency (RF) ablation catheter with a force sensor (FS) within its tip was
      used to create right atrial (RA) free wall lesions in pigs. The intact heart was
      removed and the FS-equipped catheter was used to mechanically perforate (without
      RF delivery) the free walls of both atria and ventricles: directly and through an
      introducer sheath to prevent catheter shaft buckling. Perforation was also
      performed through epicardially visible RA lesions and adjacent unablated tissue.
      Twenty-four RA free wall lesions were created in four pigs. One hundred and forty
      four mechanical perforations were performed: 44 RA, 30 left atrial (LA), 37 right
      ventricular (RV), and 33 left ventricular (LV). The RA and RV perforation force
      (PF) was lower than through the LA and LV (P<0.0001). The LV perforation time was
      shorter when the catheter was gripped through an introducer sheath (0.8+/-0.5 vs.
      3.2+/-3 s, P<0.0001). Perforation force through transmural RA lesions was lower
      than through unablated RA tissue (172.4+/-79.1 vs. 300.6+/-116.8 g, P<0.0002).
      CONCLUSION: The force threshold for mechanical perforation in the porcine heart
      is lower for right- compared with left-sided chambers, and also lower through
      recently created RA RF lesions compared with unablated RA tissue. Left
      ventricular perforation is achieved more rapidly with the ablation catheter in a
      sheath despite the same PF because the sheath prevents catheter buckling.

PMID- 21084364
TI  - Bad medicine: paediatric ear, nose, and throat surgery.

PMID- 21084362
TI  - Identification of targets for quality improvement in antimicrobial prescribing:
      the web-based ESAC Point Prevalence Survey 2009.
AB  - OBJECTIVES: Since electronic prescribing is limited to few hospitals, point
      prevalence surveys, such as the standardized European Surveillance of
      Antimicrobial Consumption point prevalence survey (ESAC PPS), are an alternative
      tool for monitoring prescribing and helping to identify performance indicators
      and prescribing trends. The main objective of this study was to identify and
      assess targets for quality improvement. METHODS: Each hospital had to carry out
      the survey within 2 weeks. Each department had to be surveyed in 1 day. Data
      collected, for all inpatients, included age and gender. For patients on systemic
      antimicrobial treatment, the antimicrobial/s, infection/prophylaxis site, reason
      in medical notes and guideline compliance were also collected. A central database
      using a web-based tool (WebPPS) developed in-house was used for data entry.
      RESULTS: Combination of two or more antimicrobials accounted for 30% of use.
      Surgical prophylaxis was prolonged (>1 day) in 53% of cases. 'Intensive care' had
      higher proportions of treated patients (53% versus 29%), combination therapy (49%
      versus 31%), hospital-acquired infections (49% versus 31%) and parenteral
      administration (91% versus 61%). 'Reason in notes' was documented in 76%, and
      'guideline compliance' occurred in 62% of patients. CONCLUSIONS: The ESAC PPS
      provided useful information on the quality of prescribing, which identified a
      number of targets for quality improvement. These could apply to specific
      departments or whole hospitals. Intensive care, which has different
      characteristics, should not be compared with general wards with respect to
      combination therapy, hospital-acquired infections or parenteral proportion. The
      study confirmed that the ESAC PPS methodology can be used on a large number of
      hospitals at regional, national, continental or global level.

PMID- 21084367
TI  - One million people to have personal care budgets by 2013.

PMID- 21084370
TI  - Gaps in information are impeding progress in cancer care in England.

PMID- 21084369
TI  - Doctors and climate change.

PMID- 21084368
TI  - Long term risk for hypertension, renal impairment, and cardiovascular disease
      after gastroenteritis from drinking water contaminated with Escherichia coli
      O157:H7: a prospective cohort study.
AB  - OBJECTIVES: To evaluate the risk for hypertension, renal impairment, and
      cardiovascular disease within eight years of gastroenteritis from drinking water
      contaminated with Escherichia coli O157:H7 and Campylobacter. DESIGN: A
      prospective cohort study. Setting Walkerton, Ontario, Canada. PARTICIPANTS: 1977
      adult participants in the Walkerton Health Study recruited between 2002 and 2005
      after an outbreak of gastroenteritis in May 2000, when a municipal water system
      was contaminated, with no pre-outbreak history of outcome measures. OUTCOME
      MEASURES: Information was collected annually via survey, physical examination,
      and laboratory assessment. Primary measures were acute gastroenteritis
      (diarrhoeal illness lasting >3 days, bloody diarrhoea, or >3 loose stools/day),
      hypertension (blood pressure >=140/90 mm Hg), and renal impairment
      (microalbuminuria or estimated glomerular filtration rate <60 ml/min/1.73 m(2)).
      Self reported physician diagnosis of cardiovascular disease (myocardial
      infarction, stroke, or congestive heart failure) was a secondary outcome.
      RESULTS: Acute gastroenteritis at the time of the outbreak was reported by 1067
      (54%) of participants. Incident hypertension was detected in 697 (35%) (294 (32%)
      of group not exposed to acute gastroenteritis v 403 (38%) of exposed group).
      While 572 (29%) had at least one indicator of renal impairment (266 (29%) of
      unexposed v 306 (29%) of exposed), only 30 (1.5%) had both (8 (0.9%) of unexposed
      v 22 (2.1%) of exposed). Cardiovascular disease was reported by 33/1749 (1.9%).
      The adjusted hazard ratios for hypertension and cardiovascular disease after
      acute gastroenteritis were 1.33 (95% confidence interval 1.14 to 1.54) and 2.13
      (1.03 to 4.43) respectively. The adjusted hazard ratio for the presence of either
      indicator of renal impairment was 1.15 (0.97 to 1.35) and was 3.41 (1.51 to 7.71)
      for the presence of both. CONCLUSION: Gastroenteritis from drinking water
      contaminated with E coli O157:H7 and Campylobacter was associated with an
      increased risk for hypertension, renal impairment, and self reported
      cardiovascular disease. Annual monitoring of blood pressure and periodic
      monitoring of renal function may be warranted for individuals who experience E
      coli O157:H7 gastroenteritis.

PMID- 21084371
TI  - Drug firm's legal action against government advisers is described as
      "intimidation".

PMID- 21084372
TI  - Screening for early detection of lung cancer.

PMID- 21084373
TI  - US medical training must adapt to reflect modern needs, say workforce planners.

PMID- 21084374
TI  - Number of deaths from cholera in Haiti nears 1000.

PMID- 21084377
TI  - Premature mortality due to stroke and trend in stroke mortality in Japan (1980
      2005).
AB  - BACKGROUND: Although a downward trend in stroke mortality over the last decades
      has been observed in many countries, stroke remains an important contributor to
      the total burden of disease. In the present study, we provided additional
      measures, namely years of life lost (YLLs) and average years of life lost (AYLLs)
      to reflect the burden of this condition in Japan. METHODS: We obtained stroke
      mortality data for Japan from the World Health Organization mortality database
      for the period 1980-2005 to analyze trends of age-standardized rates (ASRs) per
      100,000 of stroke mortality. YLLs and AYLLs were also estimated according to
      Japanese life tables. RESULTS: Decreases in ASRs by 68% in men and by 74% in
      women were observed at the end of this study period. In men, there were total of
      1,684,482 YLLs in 1980; 776,350 in 1995 and 745,636 in 2005, corresponding to an
      overall AYLLs for all stroke deaths of 20.6; 11.2 and 11.7 years earlier than
      expected, respectively. In women, the respective numbers were 1,567,817 YLLs in
      1980; 810,135 in 1995 and 726,650 in 2005, corresponding to an overall AYLLs for
      all stroke deaths of 19.4; 10.5 and 10.5 years. CONCLUSIONS: The findings showed
      shorter AYLLs due to stroke in Japan, suggesting that stroke patients died from
      this condition at older age at the end of the study period. This change in
      premature mortality was consistent with decreased trend in the stroke mortality.

PMID- 21084378
TI  - The Drosophila NR4A nuclear receptor DHR38 regulates carbohydrate metabolism and
      glycogen storage.
AB  - Animals balance nutrient storage and mobilization to maintain metabolic
      homeostasis, a process that is disrupted in metabolic diseases like obesity and
      diabetes. Here, we show that DHR38, the single fly ortholog of the mammalian
      nuclear receptor 4A family of nuclear receptors, regulates glycogen storage
      during the larval stages of Drosophila melanogaster. DHR38 is expressed and
      active in the gut and body wall of larvae, and its expression levels change in
      response to nutritional status. DHR38 null mutants have normal levels of glucose,
      trehalose (the major circulating form of sugar), and triacylglycerol but display
      reduced levels of glycogen in the body wall muscles, which constitute the primary
      storage site for carbohydrates. Microarray analysis reveals that many metabolic
      genes are mis-regulated in DHR38 mutants. These include phosphoglucomutase, which
      is required for glycogen synthesis, and the two genes that encode the digestive
      enzyme amylase, accounting for the reduced amylase enzyme activity seen in DHR38
      mutant larvae. These studies demonstrate that a critical role of nuclear receptor
      4A receptors in carbohydrate metabolism has been conserved through evolution and
      that nutritional regulation of DHR38 expression maintains the proper uptake and
      storage of glycogen during the growing larval stage of development.

PMID- 21084379
TI  - Expression and regulation of corticotropin-releasing factor receptor type 2beta
      in developing and mature mouse skeletal muscle.
AB  - Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in
      skeletal muscle (SM) tissue where it is suggested to inhibit interactions between
      insulin signaling pathway components affecting whole-body glucose homeostasis.
      However, little is known about factors regulating SM CRFR2 expression. Here, we
      demonstrate the exclusive expression of CRFR2, and not CRFR1, in mature SM tissue
      using RT-PCR and ribonuclease protection assays and report a differential
      expression of CRF receptors during C2C12 myogenic differentiation. Whereas C2C12
      myoblasts exclusively express CRFR1, the C2C12 myotubes solely express CRFR2.
      Using cAMP luciferase assays and calcium mobilization measurements, we further
      demonstrate the functionality of these differentially expressed receptors. Using
      luciferase reporter assays we show a differential activation of CRFR promoters
      during myogenic differentiation. Transfections with different fragments of the 5'
      flanking region of the mCRFR2beta gene fused to a luciferase reporter gene show a
      promoter-dependent expression of the reporter gene and reveal the importance of
      the myocyte enhancer factor 2 consensus sequence located at the 3'-proximal
      region of CRFR2beta promoter. Furthermore, we demonstrate that CRFR2 gene
      transcription in the mature mouse is stimulated by both high-fat diet and chronic
      variable stress conditions. Performing a whole-genome expression microarray
      analysis of SM tissues obtained from CRFR2-null mice or wild-type littermates
      revealed a robust reduction in retinol-binding protein 4 expression levels, an
      adipokine whose serum levels are elevated in insulin-resistant states. In
      correlation with the SM CRFR2beta levels, the SM retinol-binding protein 4 levels
      were also elevated in mice subjected to high-fat diet and chronic variable stress
      conditions. The current findings further position the SM CRFR2 pathways as a
      relevant physiological system that may affect the known reciprocal relationship
      between psychological and physiological challenges and the metabolic syndrome.

PMID- 21084380
TI  - A new, lineage specific, autoup-regulation mechanism for human glucocorticoid
      receptor gene expression in 697 pre-B-acute lymphoblastic leukemia cells.
AB  - Glucocorticoid (GC) steroid hormones induce apoptosis in acute lymphoblastic
      leukemia (ALL). Autoup-regulation of human GC receptor (hGR) levels is associated
      with sensitivity to GC-mediated apoptosis. Among the major hGR promoters
      expressed in 697 pre-B-ALL cells (1A, 1B, 1C, and 1D), only promoters 1C and 1D
      are selectively activated by the hormone. Promoter 1B is unresponsive, and
      promoter 1A is down-regulated by dexamethasone (Dex) in 697 cells, whereas they
      are both up-regulated in CEM-C7 T-ALL cells. Autoup-regulation of promoter 1C and
      1D in 697 cells requires sequences containing GC response units (GRUs) (1C GRU, 
      2915/-2956; 1D GRU, -4525/-4559) that were identified previously in CEM-C7 cells.
      These GRUs potentially bind GR, c-myeloblastosis (c-Myb), and E-twenty six (Ets)
      proteins; 697 cells express high levels of c-Myb protein, as well as the E-twenty
      six family protein members, PU.1 and Spi-B. Dex treatment in 697 cells elevates
      the expression of c-Myb and decreases levels of both Spi-B and PU.1. Chromatin
      immunoprecipitation assays revealed the specific recruitment of GR, c-Myb, and
      cAMP response element-binding protein binding protein to the 1C and 1D GRUs upon
      Dex treatment, correlating to observed autoup-regulated activity in these two
      promoters. These data suggest a hormone activated, lineage-specific mechanism to
      control the autoup-regulation of hGR gene expression in 697 pre-B-ALL cells via
      steroid-mediated changes in GR coregulator expression. These findings may be
      helpful in understanding the mechanism that determines the sensitivity of B-ALL
      leukemia cells to hormone-induced apoptosis.

PMID- 21084382
TI  - SGK3 is an estrogen-inducible kinase promoting estrogen-mediated survival of
      breast cancer cells.
AB  - Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a protein kinase of the
      AGC family of protein kinase A, protein kinase G, and protein kinase C and
      functions downstream of phosphatidylinositol 3-kinase (PI3K). Recent study
      revealed that SGK3 plays a pivotal role in Akt/protein kinase B independent
      signaling downstream of oncogenic PI3KCA mutations in breast cancer. Here we
      report that SGK3 is an estrogen receptor (ER) transcriptional target and promotes
      estrogen-mediated cell survival of ER-positive breast cancer cells. Through a
      meta-analysis on 22 microarray studies of breast cancer in the Oncomine database,
      we found that the expression of SGK3 is significantly higher (5.7-fold, P <
      0.001) in ER-positive tumors than in ER-negative tumors. In ER-positive breast
      cancer cells, SGK3 expression was found to be induced by 17beta-estradiol (E(2))
      in a dose- and time-dependent manner, and the induction of SGK3 mRNA by E(2) is
      independent of newly synthesized proteins. We identified two ERalpha-binding
      regions at the sgk3 locus through chromatin immunoprecipitation with massively
      parallel DNA sequencing. Promoter analysis revealed that ERalpha stimulates the
      activity of sgk3 promoters by interaction with these two ERalpha-binding regions
      on E(2) treatment. Loss-of-function analysis indicated that SGK3 is required for
      E(2)-mediated cell survival of MCF-7 breast carcinoma cells. Moreover,
      overexpression of SGK3 could partially protect MCF-7 cells against apoptosis
      caused by antiestrogen ICI 182,780. Together, our study defines the molecular
      mechanism of regulation of SGK3 by estrogen/ER and provides a new link between
      the PI3K pathway and ER signaling as well as a new estrogen-mediated cell
      survival mechanism mediated by SGK3 in breast cancer cells.

PMID- 21084381
TI  - Signaling from the human melanocortin 1 receptor to ERK1 and ERK2 mitogen
      activated protein kinases involves transactivation of cKIT.
AB  - Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor expressed in
      melanocytes, is a major determinant of skin pigmentation, phototype and cancer
      risk. Upon stimulation by alphaMSH, MC1R triggers the cAMP and ERK1/ERK2 MAPK
      pathways. In mouse melanocytes, ERK activation by alphaMSH binding to Mc1r
      depends on cAMP, and melanocytes are considered a paradigm for cAMP-dependent ERK
      activation. However, human MC1R variants associated with red hair, fair skin [red
      hair color (RHC) phenotype], and increased skin cancer risk display reduced cAMP
      signaling but activate ERKs as efficiently as wild type in heterologous cells,
      suggesting independent signaling to ERKs and cAMP in human melanocytes. We show
      that MC1R signaling activated the ERK pathway in normal human melanocytes and
      melanoma cells expressing physiological levels of endogenous RHC variants. ERK
      activation was comparable for wild-type and mutant MC1R and was independent on
      cAMP because it was neither triggered by stimulation of cAMP synthesis with
      forskolin nor blocked by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine.
      Stimulation of MC1R with alphaMSH did not lead to protein kinase C activation and
      ERK activation was unaffected by protein kinase C inhibitors. Conversely,
      pharmacological interference, small interfering RNA studies, expression profiles,
      and functional reconstitution experiments showed that alphaMSH-induced ERK
      activation resulted from Src tyrosine kinase-mediated transactivation of the stem
      cell factor receptor, a receptor tyrosine kinase essential for proliferation,
      differentiation, and survival of melanocyte precursors, thus demonstrating a
      functional link between the stem cell factor receptor and MC1R. Moreover, this
      transactivation phenomenon is unique because it is unaffected by natural
      mutations impairing canonical MC1R signaling through the cAMP pathway.

PMID- 21084383
TI  - Numb deletion in POMC-expressing cells impairs pituitary intermediate lobe cell
      adhesion, progenitor cell localization, and neuro-intermediate lobe boundary
      formation.
AB  - The pituitary gland contains six distinct hormone-secreting cell types that are
      essential for basic physiological processes including fertility and responding to
      stress. Formation of hormone-secreting cells during development relies on Notch
      signaling to prevent progenitors from prematurely differentiating. The nature of
      the signal curtailing Notch signaling in the pituitary is unknown, but a good
      candidate is the endocytic adaptor protein NUMB. NUMB targets Notch for
      proteolytic degradation, but it also has a broad range of actions, including
      stabilizing adherens junctions through interactions with cadherins and
      influencing cell proliferation by stabilizing expression of the tumor suppressor
      protein p53. Here, we show that NUMB and its closely related homolog, NUMBLIKE,
      are expressed in undifferentiated cells during development and later in
      gonadotropes in the anterior lobe and melanotropes of the intermediate lobe. All
      four isoforms of NUMB, are detectable in the pituitary, with the shorter forms
      becoming more prominent after adolescence. Conditionally deleting Numb and
      Numblike in the intermediate lobe melanotropes with Pomc Cre mice dramatically
      alters the morphology of cells in the intermediate lobe, coincident with impaired
      localization of adherens junctions proteins including E-CADHERIN, N-CADHERIN,
      beta-CATENIN, and alpha-CATENIN. Strikingly, the border between posterior and
      intermediate lobes is also disrupted. These mice also have disorganized
      progenitor cells, marked by SOX2, but proliferation is unaffected. Unexpectedly,
      Notch activity appears normal in conditional knockout mice. Thus, Numb is
      critical for maintaining cell-cell interactions in the pituitary intermediate
      lobe that are essential for proper cell placement.

PMID- 21084384
TI  - Interaction of glibenclamide and metformin at the level of translation in
      pancreatic beta cells.
AB  - Sulfonylurea and metformin are used in the treatment of diabetes. Their chronic
      effects on beta cells are not well known. We have shown that sustained exposure
      of rat beta cells to glibenclamide increased their protein synthesis activity,
      while metformin caused an inhibition. The effect of glibenclamide was attributed
      to an activation of translation factors. This study examines whether both drugs
      interact at the level of protein translation in beta cells. Purified rat beta
      cells were cultured with and without glibenclamide and metformin before
      measurement of protein and insulin synthesis, abundance of (phosphorylated)
      translation factors, and cell viability. A 24 h exposure to metformin stimulated
      AMP-activated protein kinase (AMPK), suppressed activation of translation factors
      both the mammalian target of rapamycin (mTOR; also known as mechanistic target
      of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding
      protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic
      elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted
      in 50% dead cells. These effects were counteracted by addition of glibenclamide,
      the action of which was blocked by the mTOR inhibitor rapamycin and the protein
      kinase A (PKA) inhibitor Rp-8-Br-cAMPs. In conclusion, metformin activates AMPK
      in beta cells leading to suppression of protein translation through mTOR
      dependent and -independent signaling. Glibenclamide antagonizes these metformin
      effects through activation of mTOR- and PKA-dependent signaling pathways.

PMID- 21084385
TI  - Kisspeptin and fertility.
AB  - The kisspeptins are a family of peptide hormones, which in recent years have been
      shown to play a critical role in the regulation of the hypothalamic-pituitary
      gonadal axis, thus in turn influencing fertility and reproduction. This review
      examines the physiological role of kisspeptin and the kisspeptin receptor in the
      control of gonadotrophin and gonadal steroid hormone secretion and the
      implications of these findings with respect to fertility. In addition, the
      potential therapeutic use of kisspeptin in the treatment of reproductive
      disorders will be examined.

PMID- 21084386
TI  - Integrins and extracellular matrix in mechanotransduction.
AB  - Integrins bind extracellular matrix fibrils and associate with intracellular
      actin filaments through a variety of cytoskeletal linker proteins to mechanically
      connect intracellular and extracellular structures. Each component of the linkage
      from the cytoskeleton through the integrin-mediated adhesions to the
      extracellular matrix therefore transmits forces that may derive from both
      intracellular, myosin-generated contractile forces and forces from outside the
      cell. These forces activate a wide range of signaling pathways and genetic
      programs to control cell survival, fate, and behavior. Additionally, cells sense
      the physical properties of their surrounding environment through forces exerted
      on integrin-mediated adhesions. This article first summarizes current knowledge
      about regulation of cell function by mechanical forces acting through integrin
      mediated adhesions and then discusses models for mechanotransduction and sensing
      of environmental forces.

PMID- 21084387
TI  - Poles apart: prokaryotic polar organelles and their spatial regulation.
AB  - While polar organelles hold the key to understanding the fundamentals of cell
      polarity and cell biological principles in general, they have served in the past
      merely for taxonomical purposes. Here, we highlight recent efforts in unraveling
      the molecular basis of polar organelle positioning in bacterial cells.
      Specifically, we detail the role of members of the Ras-like GTPase superfamily
      and coiled-coil-rich scaffolding proteins in modulating bacterial cell polarity
      and in recruiting effector proteins to polar sites. Such roles are well
      established for eukaryotic cells, but not for bacterial cells that are generally
      considered diffusion-limited. Studies on spatial regulation of protein
      positioning in bacterial cells, though still in their infancy, will undoubtedly
      experience a surge of interest, as comprehensive localization screens have
      yielded an extensive list of (polarly) localized proteins, potentially reflecting
      subcellular sites of functional specialization predicted for organelles.

PMID- 21084388
TI  - Auxin and plant-microbe interactions.
AB  - Microbial synthesis of the phytohormone auxin has been known for a long time.
      This property is best documented for bacteria that interact with plants because
      bacterial auxin can cause interference with the many plant developmental
      processes regulated by auxin. Auxin biosynthesis in bacteria can occur via
      multiple pathways as has been observed in plants. There is also increasing
      evidence that indole-3-acetic acid (IAA), the major naturally occurring auxin, is
      a signaling molecule in microorganisms because IAA affects gene expression in
      some microorganisms. Therefore, IAA can act as a reciprocal signaling molecule in
      microbe-plant interactions. Interest in microbial synthesis of auxin is also
      increasing in yet another recently discovered property of auxin in Arabidopsis.
      Down-regulation of auxin signaling is part of the plant defense system against
      phytopathogenic bacteria. Exogenous application of auxin, e.g., produced by the
      pathogen, enhances susceptibility to the bacterial pathogen.

PMID- 21084390
TI  - Characterization of 2-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-4-(4-pyridinyl)
      5-thiazolemethanol (JNJ-1930942), a novel positive allosteric modulator of the
      {alpha}7 nicotinic acetylcholine receptor.
AB  - The alpha(7) nicotinic acetylcholine receptor (nAChR) is a potential therapeutic
      target for the treatment of cognitive deficits associated with schizophrenia,
      Alzheimer's disease, Parkinson's disease, and attention-deficit/hyperactivity
      disorder. Activation of alpha(7) nAChRs improved sensory gating and cognitive
      function in animal models and in early clinical trials. Here we describe the
      novel highly selective alpha(7) nAChR positive allosteric modulator, 2-[[4-fluoro
      3-(trifluoromethyl)phenyl]amino]-4-(4-pyridinyl)-5-thiazolemethanol (JNJ
      1930942). This compound enhances the choline-evoked rise in intracellular Ca(2+)
      levels in the GH4C1 cell line expressing the cloned human alpha(7) nAChR. JNJ
      1930942 does not act on alpha4beta2, alpha3beta4 nAChRs or on the related 5-HT3A
      channel. Electrophysiological assessment in the GH4C1 cell line shows that JNJ
      1930942 increases the peak and net charge response to choline, acetylcholine, and
      N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide (PNU-282987). The
      potentiation is obtained mainly by affecting the receptor desensitization
      characteristics, leaving activation and deactivation kinetics as well as recovery
      from desensitization relatively unchanged. Choline efficacy is increased over its
      full concentration response range, and choline potency is increased more than 10
      fold. The potentiating effect is alpha(7) channel-dependent, because it is
      blocked by the alpha(7) antagonist methyllycaconitine. Moreover, in hippocampal
      slices, JNJ-1930942 enhances neurotransmission at hippocampal dentate gyrus
      synapses and facilitates the induction of long-term potentiation of electrically
      evoked synaptic responses in the dentate gyrus. In vivo, JNJ-1930942 reverses a
      genetically based auditory gating deficit in DBA/2 mice. JNJ-1930942 will be a
      useful tool to study the therapeutic potential of alpha(7) nAChR potentiation in
      central nervous system disorders in which a deficit in alpha(7) nAChR
      neurotransmission is hypothesized to be involved.

PMID- 21084391
TI  - Characterization of tumor-suppressive function of SOX6 in human esophageal
      squamous cell carcinoma.
AB  - PURPOSE: By using cDNA microarray analysis, we identified a transcriptional
      factor, SOX6, was frequently downregulated in esophageal squamous cell carcinoma
      (ESCC). The aim of this study is to investigate the role of SOX6 in human
      esophageal cancer development, and to examine the prevalence and clinical
      significance of SOX6 downregulation in ESCC. EXPERIMENTAL DESIGN: Expressions of
      SOX6 mRNA in 50 ESCCs and SOX6 protein in 300 ESCCs were investigated by
      semiquantitative RT-PCR and immunohistochemistry, respectively. The tumor
      suppressive function of SOX6 was characterized by cell growth, foci formation,
      wound-healing and cell invasive assays, and tumor xenograft experiment. Western
      blot analysis was applied to detect protein expression levels. RESULTS: SOX6 was
      frequently downregulated in primary ESCCs in both mRNA level (29/50, 58%) and
      protein level (149/219, 68.0%), which was significantly associated with the poor
      differentiation (P = 0.029), lymph node metastases (P = 0.014), advanced TNM
      stage (P = 0.000), and disease-specific survival (P < 0.001). Multivariate
      analysis indicated that the downregulation of SOX6 (P = 0.000) was a significant
      independent prognostic factors for ESCC. Functional studies showed that SOX6 was
      able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells. The
      tumor-suppressive mechanism of SOX6 was associated with its role in G1/S cell
      cycle arrest by upregulating expressions of p53 and p21(WAF1/CIP1) and
      downregulating expressions of cyclin D1/CDK4, cyclin A, and beta-catenin.
      CONCLUSIONS: We provided the first evidence that SOX6 is a novel tumor-suppressor
      gene in ESCC development and is a potential prognostic marker in ESCC.

PMID- 21084389
TI  - Developments in RNA splicing and disease.
AB  - Pre-mRNA processing, including 5'-end capping, splicing, editing, and
      polyadenylation, consists of a series of orchestrated and primarily
      cotranscriptional steps that ensure both the high fidelity and extreme diversity
      characteristic of eukaryotic gene expression. Alternative splicing and editing
      allow relatively small genomes to encode vast proteomic arrays while alternative
      3'-end formation enables variations in mRNA localization, translation, and
      stability. Of course, this mechanistic complexity comes at a high price.
      Mutations in the myriad of RNA sequence elements that regulate mRNA biogenesis,
      as well as the trans-acting factors that act upon these sequences, underlie a
      number of human diseases. In this review, we focus on one of these key RNA
      processing steps, splicing, to highlight recent studies that describe both
      conventional and novel pathogenic mechanisms that underlie muscle and
      neurological diseases.

PMID- 21084392
TI  - Acute peripheral metabolic effects of intraarterial ghrelin infusion in healthy
      young men.
AB  - CONTEXT: Ghrelin is the endogenous agonist for the growth hormone secretagogue
      receptor (GHS-R). Intravenous administration of ghrelin induces insulin
      resistance and hyperglycemia and increases the levels of free fatty acids (FFA).
      OBJECTIVE: To investigate whether these effects are mediated directly by ghrelin
      in skeletal muscle tissue. DESIGN: This study was single blinded, randomized, and
      placebo controlled. Eight healthy men (25.5 +/- 3.1 years) received 240 min of
      intraarterial ghrelin infusion (4.2 ng * kg(-1) * min(-1)) into one femoral
      artery and intraarterial placebo infusion into the contralateral artery.
      Simultaneous blood samples were drawn from both femoral veins and muscle biopsies
      were obtained from both legs during both a basal period and during a
      hyperinsulinemic and euglycemic clamp period. RESULTS: Ghrelin significantly
      elevated venous FFA levels and venous dilution of palmitate, suggestive of
      increased lipolysis. Glucose metabolism was unchanged, and there were no direct
      effects on pertinent enzymes in the insulin signaling cascade. The metabolic
      clearance rate of acyl ghrelin was 12.5 +/- 3.3 ml * kg(-1) * min(-1). Acyl and
      desacyl ghrelin levels both increased. CONCLUSIONS: The results of this study
      suggest that ghrelin may stimulate lipolysis directly in skeletal muscle.

PMID- 21084393
TI  - Type 2 diabetes (T2D) associated polymorphisms regulate expression of adjacent
      transcripts in transformed lymphocytes, adipose, and muscle from Caucasian and
      African-American subjects.
AB  - CONTEXT: Genome-wide association scans (GWAS) have identified novel single
      nucleotide polymorphisms (SNPs) that increase T2D susceptibility and indicated
      the role of nearby genes in T2D pathogenesis. OBJECTIVE: We hypothesized that T2D
      associated SNPs act as cis-regulators of nearby genes in human tissues and that
      expression of these transcripts may correlate with metabolic traits, including
      insulin sensitivity (S(I)). DESIGN, SETTINGS, AND PATIENTS: Association of SNPs
      with the expression of their nearest transcripts was tested in adipose and muscle
      from 168 healthy individuals who spanned a broad range of S(I) and body mass
      index (BMI) and in transformed lymphocytes (TLs). We tested correlations between
      the expression of these transcripts in adipose and muscle with metabolic traits.
      Utilizing allelic expression imbalance (AEI) analysis we examined the presence of
      other cis-regulators for those transcripts in TLs. RESULTS: SNP rs9472138 was
      significantly (P = 0.037) associated with the expression of VEGFA in TLs while
      rs6698181 was detected as a cis-regulator for the PKN2 in muscle (P = 0.00027)
      and adipose (P = 0.018). Significant association was also observed for rs17036101
      (P = 0.001) with expression of SYN2 in adipose of Caucasians. Among 19 GWAS
      implicated transcripts, expression of VEGFA in adipose was correlated with BMI (r
      = -0.305) and S(I) (r = 0.230). Although only a minority of the T2D-associated
      SNPs were validated as cis-eQTLs for nearby transcripts, AEI analysis indicated
      presence of other cis-regulatory polymorphisms in 54% of these transcripts.
      CONCLUSIONS: Our study suggests that a small subset of GWAS-identified SNPs may
      increase T2D susceptibility by modulating expression of nearby transcripts in
      adipose or muscle.

PMID- 21084394
TI  - Radiation exposure does not significantly contribute to the risk of recurrence of
      Chernobyl thyroid cancer.
AB  - CONTEXT: Papillary thyroid carcinoma (PTC) in patients exposed to environmental
      radioiodine after the Chernobyl accident is thought to have a relatively
      aggressive clinical course. Long-term results of treatment are not well known,
      especially in comparison with sporadic PTC. OBJECTIVE: The determination of risk
      factors for PTC recurrence in a controlled for baseline factors group of patients
      with radiation-related and sporadic PTC. DESIGN: Retrospective cohort study
      involving patients treated for PTC and followed-up in 1991-2008. Risk factors
      were assessed by stratified analysis using the proportional hazard model.
      SETTING: Referral center-based. PATIENTS: A total of 497 patients were enrolled.
      Patients exposed to radioiodine were 172 individuals with reconstructed
      individual radiation thyroid doses ranging 51-3170 mGy. Patients with sporadic
      PTC included 325 individuals matched to exposed patients for sex, age +/- 5 yr
      and time to treatment +/- 2 yr. MAIN OUTCOME MEASURE: Cancer recurrence. RESULTS:
      Nodal disease increased the recurrence rate (HR = 5.21; 95% CI = 1.63-16.7) while
      the presence of tumor capsule (HR = 0.17; 95% CI = 0.06-0.45) and, particularly,
      treatment according to the Revised American Thyroid Association Management
      Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer
      significantly reduced it (HR = 0.16; 95% CI = 0.06-0.42). None of the tested
      variables interacted with radiation factor. CONCLUSIONS: PTC developing after
      internal exposure to radioiodine does not display specific risk factors for
      recurrence different from those in sporadic PTC. Common treatment approaches for
      patients with PTC should be recommended regardless of a history of radiation
      exposure.

PMID- 21084395
TI  - Identification and functional analysis of novel human growth hormone secretagogue
      receptor (GHSR) gene mutations in Japanese subjects with short stature.
AB  - CONTEXT: Short stature (SS) is a multifactorial developmental condition with a
      significant genetic component. Recent studies have revealed that rare deleterious
      mutations in the GH-secretagogue receptor type 1A (GHSR1A) gene could be a cause
      of familial SS or GH deficiency. OBJECTIVE: The aim of this study was to evaluate
      the contribution of GHSR1A mutations to the molecular mechanism underlying SS in
      Japanese subjects. METHODS: We performed mutational screening of the GHSR1A gene
      in 127 unrelated Japanese SS patients diagnosed with either isolated GH
      deficiency or idiopathic SS. Identified mutations were analyzed in 188 control
      subjects, and their functional properties were examined in a heterologous
      expression system. RESULTS: Four novel heterozygous GHSR1A mutations were
      identified (DeltaQ36, P108L, C173R, and D246A). Expression studies demonstrated
      that these mutations had varying functional consequences: 1) all mutations showed
      a loss-of-function effect on the constitutive signaling activity of GHSR1A, but
      the degree of loss varied widely; 2) C173R caused intracellular retention of the
      mutated protein, resulting in total loss of receptor function; 3) P108L resulted
      in a large decrease in binding affinity to ghrelin, without affecting its surface
      expression; 4) D246A uniquely impaired agonist- and inverse agonist-stimulated
      receptor signaling; and 5) DeltaQ36 showed only a subtle reduction in
      constitutive activity. The cumulative frequency of these putative functional
      mutations was significantly higher in the patient group than in controls (4.72
      vs. 0.53%; P = 0.019; odds ratio = 9.28; 95% confidence interval, 1.10-78.0).
      CONCLUSIONS: Our results suggest that GHSR1A mutations contribute to the genetic
      etiology of SS in the Japanese population.

PMID- 21084396
TI  - Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and
      anticoagulant expression through secretion of TGF-beta3.
AB  - CONTEXT: Uterine leiomyomas occur in 30-70% of reproductive-age women. Leiomyoma
      reduce implantation, increase miscarriage risk, and increase menstrual bleeding.
      We hypothesized that endometrial defects induced by leiomyoma result in
      menorrhagia and reproductive dysfunction. OBJECTIVES: We evaluated the effect of
      leiomyoma on endometrial gene expression essential for implantation and
      hemostasis both in vivo and in primary endometrial stromal cells (ESC). DESIGN
      AND SETTING: We conducted a case control and in vitro study at a university
      medical center. PATIENTS: The study included 24 subjects with or without
      leiomyoma. INTERVENTION/MAIN OUTCOME MEASURED: Endometrium, myometrium,
      leiomyoma, and ESC were obtained. Immunohistochemistry was used to evaluate TGF
      beta3, bone morphogenetic protein (BMP) receptors (BMPRs), plasminogen activator
      inhibitor 1 (PAI-1), and thrombomodulin in vivo. BMP-2 secretion was assessed by
      ELISA. ESC were treated with recombinant human (rh) BMP-2 or rhTGF-beta3.
      Expression of HOXA10, LIF, BMPRs, antithrombin III (ATIII), thrombomodulin, and
      PAI-1 was assessed by quantitative RT-PCR. RESULTS: ESC from controls secreted
      more BMP-2 than those from women with leiomyoma. HOXA10 and LIF expression
      increased after rhBMP-2 treatment of normal but not leiomyoma-associated ESC. In
      vivo leiomyoma-associated endometrium expressed lower levels of BMPR 1A, 1B, and
      2 than controls. Leiomyoma expressed high levels of TGF-beta3; TGF-beta3
      treatment of ESC reduced expression of BMPRs. Similarly, leiomyoma-associated
      endometrium expressed less PAI-1 and thrombomodulin in vivo. In ESC, TGF-beta3
      reduced expression of PAI-1, ATIII, and thrombomodulin. CONCLUSIONS: Leiomyoma
      secreted TGF-beta3 induces BMP-2 resistance in endometrium by down-regulation of
      BMPR-2, likely causing defective endometrial decidualization. TGF-beta3 also
      reduces expression of PAI-1, ATIII, and thrombomodulin in endometrium, likely
      contributing to menorrhagia. A single molecular signal targeting endometrium may
      mediate both leiomyoma-induced infertility and bleeding.

PMID- 21084397
TI  - Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes
      and low serum adiponectin, but not circulating sex steroids, are strongly
      associated with insulin resistance.
AB  - CONTEXT: Comprehensive characterization of the adipose tissue in women with
      polycystic ovary syndrome (PCOS), over a wide range of body mass indices (BMIs),
      is lacking. Mechanisms behind insulin resistance in PCOS are unclear. OBJECTIVE:
      To characterize the adipose tissue of women with PCOS and controls matched pair
      wise for age and BMI, and to identify factors, among adipose tissue
      characteristics and serum sex steroids, that are associated with insulin
      sensitivity in PCOS. DESIGN/OUTCOME MEASURES: Seventy-four PCOS women and 31
      controls were included. BMI was 18-47 (PCOS) and 19-41 kg/m(2) (controls).
      Anthropometric variables, volumes of subcutaneous/visceral adipose tissue
      (magnetic resonance imaging; MRI), and insulin sensitivity (clamp) were
      investigated. Adipose tissue biopsies were obtained to determine adipocyte size,
      lipoprotein lipase (LPL) activity, and macrophage density. Circulating
      testosterone, free testosterone, free 17beta-estradiol, SHBG, glycerol,
      adiponectin, and serum amyloid A were measured/calculated. RESULTS: Comparison of
      31 pairs revealed lower insulin sensitivity, hyperandrogenemia, and higher free
      17beta-estradiol in PCOS. Abdominal adipose tissue volumes/distribution did not
      differ in the groups, but PCOS women had higher waist-to-hip ratio, enlarged
      adipocytes, reduced adiponectin, and lower LPL activity. In regression analysis,
      adipocyte size, adiponectin, and waist circumference were the factors most
      strongly associated with insulin sensitivity in PCOS (R(2)=0.681, P < 0.001).
      CONCLUSIONS: In PCOS, adipose tissue has aberrant morphology/function. Increased
      waist-to-hip ratio indicates abdominal/visceral fat accumulation, but this is not
      supported by MRI. Enlarged adipocytes and reduced serum adiponectin, together
      with a large waistline, rather than androgen excess, may be central factors in
      the pathogenesis/maintenance of insulin resistance in PCOS.

PMID- 21084399
TI  - Do the effects of testosterone on muscle strength, physical function, body
      composition, and quality of life persist six months after treatment in
      intermediate-frail and frail elderly men?
AB  - CONTEXT: Short-term testosterone (T) treatment in frail elderly men improves
      muscle mass and strength. It is unclear whether these effects can be maintained
      post treatment. OBJECTIVE: To assess the durability of androgen effects in frail
      men. DESIGN AND SETTING: Single center, randomized, double-blind, placebo
      controlled trial to investigate the effects of 6 months T (25-75 mg daily) on
      muscle strength, body composition, physical function, and quality of life (QoL).
      Participants were assessed at the end of treatment (6 months) and 6 months after
      treatment cessation (12 months). PARTICIPANTS: 274 intermediate-frail and frail
      elderly men aged 65-90 years with low T levels. RESULTS: Mean T increased from
      11.1 (3.1) nmol/liter at baseline to 18.4 (3.5) nmol/liter at 6 months, then
      declined to 10.5 (3.7) nmol/L at 12 months, in the T-treated group. Isometric
      knee extension peak torque increased in the T-treated group compared with placebo
      to give an adjusted mean difference (95% CI) between groups of 8.1 (-0.2 to 16.5)
      Nm at 6 months. Lean mass increased in the T-treated group giving a difference
      between groups of 1.2 (0.8 to 1.7) kg at 6 months. Somatic and sexual symptoms
      improved during treatment. None of these differences between groups remained at
      12 months. Prostate specific antigen (PSA) levels and haematocrit increased
      slightly during treatment but returned to baseline by 12 months. CONCLUSION: The
      effects of 6-month T treatment on muscle strength, lean mass, and QoL in frail
      men are not maintained at 6 months post treatment.

PMID- 21084398
TI  - Clinical, biochemical, and molecular characterization of macronodular
      adrenocortical hyperplasia of the zona reticularis: a new syndrome.
AB  - CONTEXT: Macronodular adrenocortical hyperplasia classically presents with
      progressive hypercortisolemia and Cushing syndrome. We describe a 29-yr-old man
      with massive macronodular adrenocortical hyperplasia without hypercortisolemia
      but rather markedly elevated and nonsuppressible production of
      dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). OBJECTIVE: To characterize
      the clinical and molecular features of this case and to determine whether the
      tissue biochemically resembles the zona reticularis or fetal adrenal. SETTING:
      University clinic, hospital, and laboratories. DESIGN: Static and dynamic blood
      and urine testing were performed preoperatively. Tissue was studied by light
      microscopy, immunoblot, RNA microarray, and enzyme assay. PARTICIPANT: A 29-yr
      old man with incidentally discovered bilateral adrenal enlargement. INTERVENTION:
      Bilateral adrenalectomy. MAIN OUTCOME MEASURES: Molecular studies compared with
      control samples. RESULTS: Hypercortisolism and 21-hydroxylase deficiency were
      excluded. DHEA, DHEAS, and 17-hydroxypregnenolone were markedly elevated and did
      not suppress with dexamethasone 2 mg/d for 4 d. Homogenates of the adrenals
      demonstrated high 17-hydroxylase, good 17,20-lyase, and low or absent 21
      hydroxylase and 3beta-hydroxysteroid dehydrogenase activities. Immunoblots
      confirmed robust expression of cytochrome P450c17 and AKR1C3 but not P450c21.
      Microarray analysis demonstrated high CYP11A1 and CYP17A1 expression but low or
      absent HSD3B1, HSD3B2, and CYP21A2 expression. Expression of mRNA for cytochrome
      b(5) (CYB5A) and AKR1C3, markers of the zona reticularis, were markedly elevated.
      CONCLUSION: This is the first case of macronodular hyperplasia of the adrenal
      zona reticularis confirmed with studies of enzyme activity, mRNA expression, and
      protein identification. We speculate that this condition can be clinically silent
      in men but might cause severe hyperandrogenemia in women.

PMID- 21084401
TI  - Ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on
      beta-cell function in individuals with impaired glucose metabolism.
AB  - CONTEXT: Pancreatic fat content (PFC) may have deleterious effects on beta-cell
      function. OBJECTIVE: We hypothesized that ectopic fat deposition, in particular
      pancreatic fat accumulation, is related to beta-cell dysfunction in individuals
      with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT).
      DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional study in 64 age- and
      body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16,
      60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was
      conducted. INTERVENTION AND MAIN OUTCOME MEASURES: Participants underwent the
      following: 1) a combined hyperinsulinemic-euglycemic and hyperglycemic clamp,
      with subsequent arginine stimulation to quantify insulin sensitivity and beta
      cell function; 2) proton-magnetic resonance spectroscopy to assess PFC and liver
      fat content (LFC); and 3) magnetic resonance imaging to quantify visceral (VAT)
      and sc (SAT) adipose tissue. The disposition index (DI; insulin sensitivity
      adjusted beta-cell function) was assessed. RESULTS: IFG and IFG/IGT were more
      insulin resistant (P < 0.001) compared with NGT. Individuals with IFG/IGT had the
      lowest values of glucose- and arginine-stimulated C-peptide secretion (both P <
      0.03) and DI (P < 0.001), relative to IFG and NGT. PFC and LFC gradually
      increased between NGT, IFG, and IFG/IGT (P = 0.02 and P = 0.01, respectively),
      whereas VAT and SAT were similar between groups. No direct associations were
      found between PFC, LFC, VAT, and SAT and C-peptide secretion. The DI was
      inversely correlated with PFC, LFC, and VAT (all P < 0.05). CONCLUSIONS: PFC was
      increased in individuals with IFG and/or IGT, without a direct relation with beta
      cell function.

PMID- 21084400
TI  - Wnt/beta-catenin pathway activation in adrenocortical adenomas is frequently due
      to somatic CTNNB1-activating mutations, which are associated with larger and
      nonsecreting tumors: a study in cortisol-secreting and -nonsecreting tumors.
AB  - BACKGROUND: Abnormal beta-catenin immunohistochemistry and mutations of the beta
      catenin gene (CTNNB1) have been reported in adrenocortical adenomas (ACAs), but
      the frequencies of these defects and the phenotype of such tumors have not been
      clearly determined. OBJECTIVE: The objective of the study was to describe the
      Wnt/beta-catenin pathway alterations in 100 ACAs and their association with
      clinicopathological characteristics. PATIENTS AND METHODS: One hundred
      consecutive ACAs (excluding Conn's adenomas) were studied clinically by beta
      catenin immunohistochemistry and direct sequencing of CTNNB1. RESULTS: Thirty
      five ACAs were nonsecreting adenomas (NSAs), 19 were subclinical cortisol
      secreting adenomas (SCSAs), and 46 were cortisol secreting adenomas (CSAs). Fifty
      one tumors had abnormal cytoplasmic and/or nuclear beta-catenin
      immunohistochemical staining, indicating Wnt/beta-catenin pathway alteration.
      Thirty-six tumors showed CTNNB1 mutations, which all showed abnormal
      immunohistochemical beta-catenin accumulation. Among the 64 nonmutated tumors,
      only 15 (23%) showed cytoplasmic and/or nuclear beta-catenin staining (P <
      0.0001). Tumors with CTNNB1 mutations were predominantly nonsecreting (61% NSAs,
      22% SCSAs, 16% CSAs) whereas nonmutated tumors were predominantly secreting (20%
      NSAs, 17% SCSAs, 62% CSAs) (P < 0.0001). Mean tumor size and weight were,
      respectively, 4.2 cm (+/- 1.3) and 28.4 g (+/- 21.4) for tumors with CTNNB1
      mutations vs. 3.4 cm (+/- 0.9) and 18.2 g (+/- 8.2) for nonmutated tumors (P <
      0.01). CONCLUSIONS: Abnormal cytoplasmic and/or nuclear beta-catenin
      immunohistochemical staining occurs in about half of ACAs. This suggests the
      activation of the Wnt/beta-catenin pathway, which could be explained by
      activating mutations of CTNNB1 in 70% of the cases. CTNNB1 mutations are mainly
      observed in larger and nonsecreting ACAs, suggesting that the Wnt/beta-catenin
      pathway activation is associated with the development of less differentiated
      ACAs.

PMID- 21084402
TI  - Small intestinal alterations in severely obese hyperglycemic subjects.
AB  - CONTEXT: Type 2 diabetes mellitus (DM2) is associated with small intestinal
      hyperplasia and hypertrophy in rodents. Moreover, the small intestine is
      increasingly acknowledged to play a role in the pathophysiology of DM2.
      OBJECTIVE: The objective of the study was to investigate the relation between
      plasma markers of small intestinal function and chronic hyperglycemia in man.
      DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional observational
      study of 40 severely obese subjects with chronic hyperglycemia and 30 severely
      obese subjects without chronic hyperglycemia who were indicated for bariatric
      surgery. MAIN OUTCOME MEASURES: We assessed plasma levels of citrulline,
      representing small intestinal enterocyte mass, intestinal fatty acid binding
      protein (I-FABP), a marker of enterocyte loss, and glucagon-like peptide-2, an
      intestinotrophic factor, and related them to glycated hemoglobin (HbA(1c))
      levels. RESULTS: Plasma citrulline and I-FABP levels were both significantly
      elevated in subjects with chronic hyperglycemia (HbA(1c) > 6.0%) compared with
      subjects with a normal HbA(1c) (<= 6.0%) (citrulline, 35 +/- 2.1 MUm vs. 26 +/-
      1.4 MUm, P = 0.001; I-FABP, 140 +/- 22 pg/ml vs. 69 +/- 14 pg/ml, P = 0.001).
      Moreover, plasma citrulline and I-FABP levels correlated with HbA(1c) levels
      (citrulline, r(s) = 0.30, P = 0.02; I-FABP, r(s) = 0.33, P = 0.005). The I-FABP
      to citrulline ratio was higher in subjects with an elevated HbA(1c) (4.0 vs. 3.1,
      P = 0.03). Plasma glucagon-like peptide-2 levels were not related to citrulline
      or I-FABP levels (r(s) = 0.06, P = 0.67; r(s) 0.08, P = 0.54, respectively).
      CONCLUSION: Chronically elevated glucose levels in obese individuals are
      associated with increased small intestinal enterocyte mass and increased
      enterocyte loss. These findings argue for the further exploration of the role of
      the intestine in the pathophysiology of DM2.

PMID- 21084403
TI  - Inflammatory and oxidative stress markers after intravenous insulin in
      percutaneous coronary intervention with stent in type 2 diabetes mellitus: a
      randomized controlled trial.
AB  - CONTEXT/OBJECTIVE: The objective of the study was to evaluate the effects of
      normalizing glycemia through iv insulin per 24 h on markers of oxidative stress
      and inflammation in patients with diabetes submitted to percutaneous coronary
      intervention (PCI) with stent. PATIENTS/METHODS: This was a prospective, open
      label, randomized controlled trial, comparing continuous iv insulin per 24 h
      targeting glycemia less than 110 mg/dl iv insulin treatment (IIT; n = 35) to
      standard treatment (ST; n = 35, regular insulin if glycemia was greater than 200
      mg/dl). Blood samples for glycemia, glycated hemoglobin, lipids, inflammatory
      markers [C-reactive protein (CRP), soluble CD40 ligand, IL-6, and endothelin 1
      (ET-1)] and oxidative stress (total antioxidant status, carbonyl) were collected
      immediately after and 24 h after PCI. RESULTS: Seventy patients were included.
      Mean age was 60.5 +/- 10 yr, 60% were men, glycated hemoglobin was 8.1 +/- 1.8
      (IIT) vs. 7.6 +/- 1.6% (ST) (P = 0.39). The intensive insulin group had lower
      glycemia (P = 0.006) and higher insulinemia (P < 0.001). Insulin did not change
      CRP [4.5 (2.1-11.7) vs. 6.8 (2.4-10.3), P = 0.35], soluble CD40 ligand [402 (191
      843) vs. 610 (230-1200), P = 0.68], IL-6 [6.21 (3.1.-10.4) vs. 10.37 (5.9-15.3),
      P = 0.09], and ET-1 [1.02 (0.7-1.8) vs. 1.10 (0.7-1.9), P = 0.657]. CRP, IL-6,
      and ET-1 increased after PCI in both groups (P < 0.05). No change was observed on
      protein oxidation (carbonyl, P = 0.70; total antioxidant status, P = 0.33). There
      was a positive correlation between CRP and glycemia (r = 0.29, P = 0.002).
      CONCLUSIONS: Continuous iv insulin for 24 h increased insulin levels and
      prevented hyperglycemia. Insulin infusion did not prevent the rise in
      inflammatory and oxidative stress markers, and no differences were observed
      between IIT and ST after PCI with a stent.

PMID- 21084404
TI  - Nitrogen and water addition reduce leaf longevity of steppe species.
AB  - BACKGROUND AND AIMS: Changes in supplies of resources will modify plant
      functional traits. However, few experimental studies have addressed the effects
      of nitrogen and water variations, either singly or in combination, on functional
      traits. METHODS: A 2-year field experiment was conducted to test the effects of
      nitrogen and water addition on leaf longevity and other functional traits of the
      two dominant (Agropyron cristatum and Stipa krylovii) and three most common
      species (Cleistogenes squarrosa, Melilotoides ruthenica and Potentilla
      tanacetifolia) in a temperate steppe in northern China. KEY RESULTS: Additional
      nitrogen and water increased leaf nitrogen content and net photosynthetic rate,
      and changed other measured functional traits. Leaf longevity decreased
      significantly with both nitrogen addition (-6 days in 2007 and -5.4 days in 2008;
      both P < 0.001) and watering (-13 days in 2007 and -9.9 days in 2008; both P <
      0.001), and significant differences in leaf longevity were also found among
      species. Nitrogen and water interacted to affect leaf longevity and other
      functional traits. Soil water content explained approx. 70 % of the shifts in
      leaf longevity. Biomass at both species and community level increased under water
      and nitrogen addition because of the increase in leaf biomass production per
      individual plant. CONCLUSIONS: The results suggest that additional nitrogen and
      water supplies reduce plant leaf longevity. Soil water availability might play a
      fundamental role in determining leaf longevity and other leaf functional traits,
      and its effects can be modified by soil nitrogen availability in semi-arid areas.
      The different responses of species to resource alterations may cause different
      global change ramifications under future climate change scenarios.

PMID- 21084405
TI  - A novel alpha-D-galactosynthase from Thermotoga maritima converts beta-D
      galactopyranosyl azide to alpha-galacto-oligosaccharides.
AB  - The large-scale production of oligosaccharides is a daunting task, hampering the
      study of the role of glycans in vivo and the testing of the efficacy of novel
      glycan-based drugs. Glycosynthases, mutated glycosidases that synthesize
      oligosaccharides in high yields, are becoming important chemo-enzymatic tools for
      the production of oligosaccharides. However, while beta-glycosynthase can be
      produced with a rather well-established technology, examples of alpha
      glycosynthases are thus far limited only to enzymes from glycoside hydrolase 29
      (GH29), GH31 and GH95 families. alpha-L-Fucosynthases from GH29 use convenient
      glycosyl azide derivatives as a strategic alternative to glycosyl fluoride
      donors. However, the general applicability of this method to other alpha
      glycosynthases is not trivial and remains to be confirmed. Here, beta-D
      galactopyranosyl azide was converted to alpha-galacto-oligosaccharides with good
      yields and high regioselectivity, catalyzed by a novel alpha-galactosynthase
      based on the GH36 alpha-galactosidase from the hyperthermophilic bacterium
      Thermotoga maritima. These results open a new avenue to the practical synthesis
      of biologically interesting alpha-galacto-oligosaccharides and demonstrate more
      widespread use of beta-glycosyl-azide as donors, confirming their utility to
      expand the repertoire of glycosynthases.

PMID- 21084406
TI  - Changes in angiotensin receptors expression play a pivotal role in the renal
      damage observed in spontaneously hypertensive rats.
AB  - The renal renin-angiotensin system plays a central role in the development of
      hypertension. The aim of this work was to verify the expression of angiotensin II
      receptors AT(1)R and AT(2)R in the microsomal fraction of renal cortex and
      correlate this with the development of hypertension and renal damage in
      spontaneously hypertensive rats (SHR) using Wistar-Kyoto rats (WKY) as controls.
      AT(1)R expression increased (126%) and AT(2)R expression decreased (66%) in 4-wk
      old SHR; AT(2) expression decreased in 14-wk-old SHR (61%) compared with
      respective age-matched WKY. These modifications were correlated to the increase
      in protein kinase C activity and decrease in protein kinase A activity. Four-week
      old SHR showed large accumulations of macrophages in kidney glomerulus and the
      tubulointerstitial area, dense cortical collagen deposition, and arterial
      proliferative changes in the walls of arterioles and medium-sized vessels.
      Similar modifications were also observed in 14-wk-old SHR. Four-week-old SHR
      treated with losartan (30 mg.kg(-1).day(-1)) or hydralazine (15 and 30 mg.kg(
      1).day(-1)) by gavage for 10 wk did not develop hypertension. The decrease in
      AT(2)R expression and renal damage observed in SHR remained even after treatment
      with hydralazine. On the other hand, losartan treatment prevented the
      modifications observed in 14-wk-old SHR, indicating that renal injuries are
      caused specifically by AT(1) rather than an increase in blood pressure. Our
      results indicate that the imbalance in AT(1)R and AT(2)R expression is associated
      with an inflammatory process that contributes to renal injury in adult SHR and to
      the development of hypertension.

PMID- 21084407
TI  - Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an
      orthologous PCK rat model of autosomal-recessive polycystic kidney disease.
AB  - In polycystic kidney disease (PKD), cyst lining cells show polarity
      abnormalities. Recent studies have demonstrated loss of cell contact in cyst
      cells, suggesting induction of epithelial-to-mesenchymal transition (EMT).
      Recently, EMT has been implicated in the pathogenesis of PKD. To explore further
      evidence of EMT in PKD, we examined age- and segment-specific expression of
      adhesion molecules and mesenchymal markers in PCK rats, an orthologous model of
      human autosomal-recessive PKD. Kidneys from 5 male PCK and 5 control rats each at
      0 days, 1, 3, 10, and 14 wk, and 4 mo of age were serially sectioned and stained
      with segment-specific markers and antibodies against E-cadherin, Snail1, beta
      catenin, and N-cadherin. mRNAs for E-cadherin and Snail1 were quantified by real
      time PCR. Vimentin, fibronectin, and alpha-smooth muscle actin (alpha-SMA)
      expressions were assessed as mesenchymal markers. E-cadherin expression pattern
      was correlated with the disease pathology in that tubule segments showing the
      highest expression in control had much severer cyst formation in PCK rats. In PCK
      rats, E-cadherin and beta-catenin in cystic tubules was attenuated and localized
      to lateral areas of cell-cell contact, whereas nuclear expression of Snail1
      increased in parallel with cyst enlargement. Some epithelial cells in large cysts
      derived from these segments, especially in adjacent fibrotic areas, showed
      positive immunoreactivity for vimentin and fibronectin. In conclusion, these
      findings suggest that epithelial cells in cysts acquire mesenchymal features in
      response to cyst enlargement and participate in progressive renal fibrosis. Our
      study clarified the nephron segment-specific cyst profile related to EMT in PCK
      rats. EMT may play a key role in polycystic kidney disease.

PMID- 21084409
TI  - Incremental benefit of computer-aided detection when used as a second and
      concurrent reader of CT colonographic data: multiobserver study.
AB  - PURPOSE: To quantify the changes in reader performance levels, if any, during
      interpretation of computed tomographic (CT) colonographic data when a computer
      aided detection (CAD) system is used as a second or concurrent reader. MATERIALS
      AND METHODS: After institutional review board approval was obtained, 16
      experienced radiologists searched for polyps in 112 patients, 56 of whom had 132
      polyps. Each case was interpreted on three separate occasions by using an
      unassisted (without CAD), second-read CAD, or concurrent CAD reading paradigm.
      The reading paradigm and case order were randomized, with a minimal interval of 1
      month between consecutive interpretations. The readers' findings were compared
      with the reference-truth interpretation. The mean per-patient sensitivity and
      mean per-patient specificity with CAD were compared with those achieved with
      unassisted reading. An increase in per-patient sensitivity was considered to be
      clinically more important than an equivalent decrease in specificity. RESULTS:
      The mean per-patient sensitivity for identification of patients with polyps of
      any size increased significantly with use of second-read CAD (mean increase,
      7.0%; 95% confidence interval [CI]: 4.0%, 9.8%) and concurrent CAD (mean
      increase, 4.5%; 95% CI: 0.8%, 8.2%). The mean per-patient specificity did not
      decrease significantly with use of second-read CAD (mean decrease, -2.5%; 95% CI:
      -5.2%, 0.1%) or concurrent CAD (mean decrease, -2.2%; 95% CI: -4.6%, 0.2%). With
      analysis restricted to patients with polyps 6 mm or larger, the benefit in
      sensitivity with second-read CAD remained (mean increase, 7.1%; 95% CI: 3.0%,
      11.1%), whereas the increase with concurrent CAD was not significant (mean
      increase, 4.2%; 95% CI: -0.5%, 8.9%). Use of second-read CAD significantly
      increased the per-polyp sensitivity for polyps 6 mm or larger (mean increase,
      9.0%; 98.3% CI: 4.9%, 12.8%) and polyps 5 mm or smaller (mean increase, 5.9%;
      98.3% CI: 3.2%, 9.1%), but use of concurrent CAD increased the per-polyp
      sensitivity for only those polyps 5 mm or smaller (mean increase, 4.8%; 98.3% CI:
      2.2%, 7.9%). CONCLUSION: Use of second-read CAD significantly improves readers'
      per-patient and per-polyp detection. Concurrent CAD is less effective.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100354/-/DC1.

PMID- 21084408
TI  - Cellular mechanisms underlying nitric oxide-induced vasodilation of descending
      vasa recta.
AB  - It has been observed that vasoactivity of explanted descending vasa recta (DVR)
      is modulated by intrinsic nitric oxide (NO) and superoxide (O(2)(-)) production
      (Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai CY, Patzak A, Pallone TL.
      Am J Physiol Renal Physiol 299: F1056-F1064, 2010). To elucidate the cellular
      mechanisms by which NO, O(2)(-) and hydrogen peroxide (H(2)O(2)) modulate DVR
      pericyte cytosolic Ca(2+) concentration ([Ca](cyt)) and vasoactivity, we expanded
      our mathematical model of Ca(2+) signaling in pericytes. We incorporated
      simulations of the pathways that translate an increase in [Ca](cyt) to the
      activation of myosin light chain (MLC) kinase and cell contraction, as well as
      the kinetics of NO and reactive oxygen species formation and their effects on
      [Ca](cyt) and MLC phosphorylation. The model reproduced experimentally observed
      trends of DVR vasoactivity that accompany exposure to N(omega)-nitro-L-arginine
      methyl ester, 8-Br-cGMP, Tempol, and H(2)O(2). Our results suggest that under
      resting conditions, NO-induced activation of cGMP maintains low levels of
      [Ca](cyt) and MLC phosphorylation to minimize basal tone. This results from
      stimulation of Ca(2+) uptake from the cytosol into the SR via SERCA pumps, Ca(2+)
      efflux into the extracellular space via plasma membrane Ca(2+) pumps, and MLC
      phosphatase (MLCP) activity. We predict that basal concentrations of O(2)(-) and
      H(2)O(2) have negligible effects on Ca(2+) signaling and MLC phosphorylation. At
      concentrations above 1 nM, O(2)(-) is predicted to modulate [Ca(cyt)] and MCLP
      activity mostly by reducing NO bioavailability. The DVR vasoconstriction that is
      induced by high concentrations of H(2)O(2) can be explained by H(2)O(2)-mediated
      downregulation of MLCP and SERCA activity. We conclude that intrinsic generation
      of NO by the DVR wall may be sufficient to inhibit vasoconstriction by
      maintaining suppression of MLC phosphorylation.

PMID- 21084410
TI  - Image Wisely: a campaign to increase awareness about adult radiation protection.

PMID- 21084411
TI  - Transmission of nonemergent critical findings: communication versus consultation.

PMID- 21084413
TI  - Safety, efficacy, and indications of beta-adrenergic receptor blockade to reduce
      heart rate prior to coronary CT angiography.
AB  - For selected indications, coronary computed tomographic (CT) angiography is an
      established clinical technology for evaluation in patients suspected of having or
      known to have coronary artery disease. In coronary CT angiography, image quality
      is highly dependent on heart rate, with heart rate reduction to less than 60
      beats per minute being important for both image quality and radiation dose
      reduction, especially when single-source CT scanners are used. beta-Blockers are
      the first-line option for short-term reduction of heart rate prior to coronary CT
      angiography. In recent years, multiple beta-blocker administration protocols with
      oral and/or intravenous application have been proposed. This review article
      provides an overview of the indications, efficacy, and safety of beta-blockade
      protocols prior to coronary CT angiography with respect to different scanner
      techniques. Moreover, implications for radiation exposure and left ventricular
      function analysis are discussed.

PMID- 21084414
TI  - Imaging in interventional oncology.
AB  - Medical imaging in interventional oncology is used differently than in diagnostic
      radiology and prioritizes different imaging features. Whereas diagnostic imaging
      prioritizes the highest-quality imaging, interventional imaging prioritizes real
      time imaging with lower radiation dose in addition to high-quality imaging. In
      general, medical imaging plays five key roles in image-guided therapy, and
      interventional oncology, in particular. These roles are (a) preprocedure
      planning, (b) intraprocedural targeting, (c) intraprocedural monitoring, (d)
      intraprocedural control, and (e) postprocedure assessment. Although many of these
      roles are still relatively basic in interventional oncology, as research and
      development in medical imaging focuses on interventional needs, it is likely that
      the role of medical imaging in intervention will become even more integral and
      more widely applied. In this review, the current status of medical imaging for
      intervention in oncology will be described and directions for future development
      will be examined.

PMID- 21084415
TI  - Diffusion-weighted MR imaging of the placenta in fetuses with placental
      insufficiency.
AB  - PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging of the
      human placenta in fetuses with and fetuses without intrauterine growth
      restriction (IUGR) who were suspected of having placental insufficiency.
      MATERIALS AND METHODS: The study was approved by the local ethics committee, and
      written informed consent was obtained. The authors retrospectively evaluated 1.5
      T fetal MR images from 102 singleton pregnancies (mean gestation +/- standard
      deviation, 29 weeks +/- 5; range, 21-41 weeks). Morphologic and diffusion
      weighted MR imaging were performed. A region of interest analysis of the apparent
      diffusion coefficient (ADC) of the placenta was independently performed by two
      observers who were blinded to clinical data and outcome. Placental insufficiency
      was diagnosed if flattening of the growth curve was detected at obstetric
      ultrasonography (US), if the birth weight was in the 10th percentile or less, or
      if fetal weight estimated with US was below the 10th percentile. Abnormal
      findings at Doppler US of the umbilical artery and histopathologic examination of
      specimens from the placenta were recorded. The ADCs in fetuses with placental
      insufficiency were compared with those in fetuses of the same gestational age
      without placental insufficiency and tested for normal distribution. The t tests
      and Pearson correlation coefficients were used to compare these results at 5%
      levels of significance. RESULTS: Thirty-three of the 102 pregnancies were
      ultimately categorized as having an insufficient placenta. MR imaging depicted
      morphologic changes (eg, infarction or bleeding) in 27 fetuses. Placental
      dysfunction was suspected in 33 fetuses at diffusion-weighted imaging (mean ADC,
      146.4 sec/mm(2) +/- 10.63 for fetuses with placental insufficiency vs 177.1
      sec/mm(2) +/- 18.90 for fetuses without placental insufficiency; P < .01, with
      one false-positive case). The use of diffusion-weighted imaging in addition to US
      increased sensitivity for the detection of placental insufficiency from 73% to
      100%, increased accuracy from 91% to 99%, and preserved specificity at 99%.
      CONCLUSION: Placental dysfunction associated with growth restriction is
      associated with restricted diffusion and reduced ADC. A decreased ADC used as an
      early marker of placental damage might be indicative of pregnancy complications
      such as IUGR. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092283/-/DC1.

PMID- 21084416
TI  - Mock trial at 2009 RSNA annual meeting: Jury exonerates radiologist for failure
      to communicate abnormal finding--but....
AB  - On the morning of Sunday November 29, 2009, hundreds of radiologist-attendees at
      the Radiological Society of North America's Scientific Assembly and Annual
      Meeting took their seats in a simulated courtroom at McCormick Place, Chicago,
      Ill, to witness a mock trial of a radiologist who had been accused of medical
      malpractice for failing to communicate to a referring physician a possibly
      important abnormal radiologic finding. This report is a summary of the lawsuit.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100927/-/DC1.

PMID- 21084417
TI  - Validation of computational fluid dynamics in CT-based airway models with
      SPECT/CT.
AB  - PURPOSE: To compare the results obtained by using numerical flow simulations with
      the results of combined single photon emission computed tomography (SPECT) and
      computed tomography (CT) and to demonstrate the importance of correct boundary
      conditions for the numerical methods to account for the large amount of
      interpatient variability in airway geometry. MATERIALS AND METHODS: This study
      was approved by all relevant institutional review boards. All patients gave their
      signed informed consent. In this study, six patients with mild asthma (three men;
      three women; overall mean age, 46 years +/- 17 [standard deviation]) underwent CT
      at functional residual capacity and total lung capacity, as well as SPECT/CT. CT
      data were used for segmentation and computational fluid dynamics (CFD)
      simulations. A comparison was made between airflow distribution, as derived with
      (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar
      expansion measurement, and (c) CFD through flow computer simulation. Also, the
      heterogeneity of the ventilation was examined. RESULTS: Good agreement was found
      between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot
      detection. The average difference for the internal airflow distribution was less
      than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns
      could be detected with SPECT/CT and CFD. CONCLUSION: This results of this study
      show that patient-specific computer simulations with appropriate boundary
      conditions yield information that is similar to that obtained with functional
      imaging tools, such as SPECT/CT. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100322/-/DC1.

PMID- 21084419
TI  - Case 164: Funicular type of spermatic cord hydrocele.

PMID- 21084420
TI  - Identifying patients with atypical ductal hyperplasia diagnosed at core-needle
      biopsy who are at low risk of malignancy.

PMID- 21084421
TI  - Cement leakage or not?

PMID- 21084422
TI  - Helical-shaped streamlines do not represent helical flow.

PMID- 21084423
TI  - Bland-Altman plots and receiver operating characteristic curves are preferred.

PMID- 21084424
TI  - The impact of graphic cigarette warning labels and smoke-free law on health
      awareness and thoughts of quitting in Taiwan.
AB  - The present study evaluated the impact of Taiwan's graphic cigarette warning
      labels and smoke-free law on awareness of the health hazards of smoking and
      thoughts of quitting smoking. National representative samples of 1074 and 1094
      people, respectively, were conducted successfully by telephone in July 2008 (pre
      law) and March 2009 (post-law). Results reveal that the prevalence of thinking
      about the health hazards of smoking among smokers increased from 50.6% pre-law to
      79.6% post-law, while the prevalence among non-smokers increased from 68.8 to
      94.1% during the same period. The prevalence rates of smokers who reported
      thinking of quitting rose from 30.2% pre-law to 51.7% post-law. Multivariate
      analyses results indicated that the implementation of graphic warning labels and
      the smoke-free law significantly increased the odds of awareness about the health
      hazards of smoking [odds ratio (OR) = 6.39, 95% confidence interval (CI) = 4.84
      8.44] and thoughts of quitting smoking (OR = 2.39, 95% CI = 1.48-3.87). In
      conclusion, the implementation of a smoke-free law in combination with graphic
      cigarette warning labels has been effective in increasing thoughts about the
      health hazards of smoking and quitting smoking.

PMID- 21084425
TI  - Proteasome inhibition improves the muscle of laminin alpha2 chain-deficient mice.
AB  - Muscle atrophy, a significant characteristic of congenital muscular dystrophy
      with laminin alpha2 chain deficiency (also known as MDC1A), occurs by a change in
      the normal balance between protein synthesis and protein degradation. The
      ubiquitin-proteasome system (UPS) plays a key role in protein degradation in
      skeletal muscle cells. In order to identify new targets for drug therapy against
      MDC1A, we have investigated whether increased proteasomal degradation is a
      feature of MDC1A. Using the generated dy(3K)/dy(3K) mutant mouse model of MDC1A,
      we studied the expression of members of the ubiquitin-proteasome pathway in
      laminin alpha2 chain-deficient muscle, and we treated dy(3K)/dy(3K) mice with the
      proteasome inhibitor MG-132. We show that members of the UPS are upregulated and
      that the global ubiquitination of proteins is raised in dystrophic limb muscles.
      Also, phosphorylation of Akt is diminished in diseased muscles. Importantly,
      proteasome inhibition significantly improves the dystrophic dy(3K)/dy(3K)
      phenotype. Specifically, treatment with MG-132 increases lifespan, enhances
      locomotive activity, enlarges muscle fiber diameter, reduces fibrosis, restores
      Akt phosphorylation and decreases apoptosis. These studies promote better
      understanding of the disease process in mice and could lead to a drug therapy for
      MDC1A patients.

PMID- 21084427
TI  - The effect of a Radiology Conference consultation on cancer patients management.
AB  - BACKGROUND: The quantitative effect of consultation on cancer patient's
      management at a Radiology Conference was studied. PATIENTS AND METHODS: This
      prospective study included consecutive patients presented at the Radiology
      Conference of the Division of Oncology. Following the case presentation and
      discussion, the patient's oncologist completed a questionnaire which asked
      whether the consultation at the conference added new information regarding the
      patient's disease status, whether it influenced patient management and, if so, to
      what extent. RESULTS: Three hundred and eighty-three patients were included in
      the study. Significant new information was added for 189 (49%) patients and less
      consequential information was added for 134 (35%) patients. Major changes in
      management occurred in 143 (37%) patients after the Radiology Conference and
      minor changes were made in 56 (15%) patients. The influence of the cancer type on
      the rate of significant change in treatment and on the rate of major information
      addition was not statistically significant. CONCLUSION: Consultation at a
      Radiological Conference in a tertiary center led to major changes in the
      management of 37% of the cancer patients presented and provided important
      information regarding the patient's disease in up to 50% of patients.

PMID- 21084426
TI  - Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the
      risk loci for Parkinson's disease in the European population.
AB  - We performed a three-stage genome-wide association study (GWAS) to identify
      common Parkinson's disease (PD) risk variants in the European population. The
      initial genome-wide scan was conducted in a French sample of 1039 cases and 1984
      controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs
      at SNCA were found to be associated with PD at the genome-wide significance level
      (P < 3 * 10(-8)). An additional set of promising and new association signals was
      identified and submitted for immediate replication in two independent case
      control studies of subjects of European descent. We first carried out an in
      silico replication study using GWAS data from the WTCCC2 PD study sample (1705
      cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in
      a third sample of 1527 cases and 1864 controls from France and Australia. We
      found converging evidence of association with PD on 12q24 (rs4964469, combined P
      = 2.4 * 10(-7)) and confirmed the association on 4p15/BST1 (rs4698412, combined P
      = 1.8 * 10(-6)), previously reported in Japanese data. The 12q24 locus includes
      RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription
      factors that regulate many genes involved in brain morphogenesis and
      intracellular calcium homeostasis.

PMID- 21084429
TI  - Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel
      with planned crossover to the alternate single agent in metastatic breast cancer.
AB  - BACKGROUND: Safety and efficacy of gemcitabine plus docetaxel (GD) and
      capecitabine plus docetaxel (CD) were compared in patients with metastatic breast
      cancer, where the alternate crossover monotherapy (GD->C or CD->G) was
      predetermined. PATIENTS AND METHODS: Patients were randomly assigned to 3-week
      cycles of either gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 75
      mg/m(2) on day 1 or capecitabine 1000 mg/m(2) twice daily on days 1-14 plus
      docetaxel 75 mg/m(2) day 1. Upon progression, patients received crossover
      monotherapy. Primary end point was time to progression (TtP). Secondary end
      points evaluated overall response rate (ORR), overall survival (OS), and adverse
      events (AEs). RESULTS: Despite over-accrual of 475 patients, the trial matured
      with only 324 of 385 planned TtP events due to patient discontinuations. Human
      epidermal growth factor receptor 2 status was not captured in this study. More CD
      patients (28%) discontinued due to AEs than GD patients (18.0%, P = 0.009). TtP
      [hazard ratio (HR) = 1.101, 95% confidence interval (CI) 0.885-1.370, P = 0.387]
      and OS (HR = 1.031, 95% CI 0.830-1.280, P = 0.785) were not significantly
      different comparing GD and CD. ORR was not statistically different (P = 0.239)
      comparing GD (72 of 207, 34.8%) and CD (78 of 191, 40.8%). TtP, OS, and ORR were
      not significantly different comparing crossover groups. GD caused greater
      fatigue, hepatotoxicity, neutropenia, and thrombocytopenia but not febrile
      neutropenia; CD caused more hand-foot syndrome, gastrointestinal toxicity, and
      mucositis. CONCLUSIONS: GD and CD produced similar efficacy and toxicity profiles
      consistent with prior clinical experience.

PMID- 21084428
TI  - Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA
      mutation status and platinum sensitivity.
AB  - BACKGROUND: Patients with BRCA-associated ovarian cancer (OC) have a survival
      advantage over those with sporadic OC. To further explore this, we examined the
      impact of prognostic factors on disease-free survival (DFS) and overall survival
      (OS) in patients with known BRCA mutation status. PATIENTS AND METHODS: We
      reviewed stage III-IV OC patients treated at our institution between 1 December
      1996 and 30 September 2006 and also tested on protocol for BRCA mutations. Impact
      on DFS and OS was determined by Kaplan-Meier analysis and a Cox proportional
      hazards model. RESULTS: Of the 110 patients, 36 had deleterious BRCA mutations
      [BRCA (+)] and 74 were BRCA wild type [BRCA(-)]. Thirty-one of 36 (86%) BRCA (+)
      and 60 of 74 (81%) BRCA (-) patients were platinum sensitive (P = 0.60). Median
      OS was longer for BRCA (+) patients (not reached versus 67.8 months; P = 0.02),
      but DFS was similar (26.9 versus 24.0, P = 0.3). On multivariate analysis, OS
      correlated with primary platinum sensitivity [HR = 0.15; 95% CI (confidence
      interval) 0.06-0.34] and BRCA (+) mutation status (HR = 0.33; 95% CI 0.12-0.86).
      CONCLUSIONS: BRCA mutation status predicted OS independent of primary platinum
      sensitivity, suggesting that underlying tumor biology contributes to disease
      outcome and may be worthy of consideration in future clinical trial design.

PMID- 21084430
TI  - Genetic association mapping identifies single nucleotide polymorphisms in genes
      that affect abscisic acid levels in maize floral tissues during drought.
AB  - In maize, water stress at flowering causes loss of kernel set and productivity.
      While changes in the levels of sugars and abscisic acid (ABA) are thought to play
      a role in this stress response, the mechanistic basis and genes involved are not
      known. A candidate gene approach was used with association mapping to identify
      loci involved in accumulation of carbohydrates and ABA metabolites during stress.
      A panel of single nucleotide polymorphisms (SNPs) in genes from these metabolic
      pathways and in genes for reproductive development and stress response was used
      to genotype 350 tropical and subtropical maize inbred lines that were well
      watered or water stressed at flowering. Pre-pollination ears, silks, and leaves
      were analysed for sugars, starch, proline, ABA, ABA-glucose ester, and phaseic
      acid. ABA and sugar levels in silks and ears were negatively correlated with
      their growth. Association mapping with 1229 SNPs in 540 candidate genes
      identified an SNP in the maize homologue of the Arabidopsis MADS-box gene,
      PISTILLATA, which was significantly associated with phaseic acid in ears of well
      watered plants, and an SNP in pyruvate dehydrogenase kinase, a key regulator of
      carbon flux into respiration, that was associated with silk sugar concentration.
      An SNP in an aldehyde oxidase gene was significantly associated with ABA levels
      in silks of water-stressed plants. Given the short range over which decay of
      linkage disequilibrium occurs in maize, the results indicate that allelic
      variation in these genes affects ABA and carbohydrate metabolism in floral
      tissues during drought.

PMID- 21084431
TI  - Upregulation of RhoB via c-Jun N-terminal kinase signaling induces apoptosis of
      the human gastric carcinoma NUGC-3 cells treated with NSC12618.
AB  - RhoB expression is reduced in most invasive tumors, with loss of RhoB expression
      correlating significantly with tumor stage. Here, we demonstrate that
      upregulation of RhoB by the potent anticancer agent NSC126188 induces apoptosis
      of NUGC-3 human gastric carcinoma cells. The crucial role of RhoB in NSC126188
      induced apoptosis is indicated by the rescue of NUGC-3 cells from apoptosis by
      knockdown of RhoB. In the presence of NSC126188, c-Jun N-terminal kinase (JNK)
      signaling was activated, and the JNK inhibitor SP600125 reduced RhoB expression
      and suppressed the apoptosis of NUGC-3 cells. Knockdowns of mitogen-activated
      protein kinase kinase (MKK) 4/7, JNK1/2 and c-Jun downregulated RhoB expression
      and rescued cells from apoptotic death in the presence of NSC126188. The JNK
      inhibitor SP600125 suppressed transcriptional activation of RhoB in the presence
      of NSC126188, as indicated by a reporter assay that used luciferase under the
      RhoB promoter. The ability of NSC126188 to increase luciferase activity through
      both the p300-binding site and the inverted CCAAT sequence (iCCAAT box) suggests
      that JNK signaling to upregulate RhoB expression is mediated through both the
      p300-binding site and the iCCAAT box. However, the JNK inhibitor SP600125 did not
      inhibit the upregulation of RhoB by farnesyltransferase inhibitor (FTI)-277. The
      p300-binding site did not affect activation of the RhoB promoter by FTI-277 in
      NUGC-3 cells, suggesting that the transcriptional activation of RhoB by NSC126188
      occurs by a different mechanism than that reported for FTIs. Our data indicate
      that NSC126188 increases RhoB expression via JNK-mediated signaling through a
      p300-binding site and iCCAAT box resulting in apoptosis of NUGC-3 cells.

PMID- 21084432
TI  - Coexposure to mercury increases immunotoxicity of trichloroethylene.
AB  - We have shown previously that chronic (32 weeks) exposure to occupationally
      relevant concentrations of the environmental pollutant trichloroethylene (TCE)
      induced autoimmune hepatitis (AIH) in autoimmune-prone MRL+/+ mice. In real-life,
      individuals are never exposed to only one chemical such as TCE. However, very
      little is known about the effects of chemical mixtures on the immune system. The
      current study examined whether coexposure to another known immunotoxicant,
      mercuric chloride (HgCl(2)), altered TCE-induced AIH. Female MRL+/+ mice were
      treated for only 8 weeks with TCE (9.9 or 186.9 mg/kg/day in drinking water)
      and/or HgCl(2) (260 MUg/kg/day, sc). Unlike mice exposed to either TCE or HgCl(2)
      alone, mice exposed to both toxicants for 8 weeks developed significant liver
      pathology commensurate with early stages of AIH. Disease development in the
      coexposed mice was accompanied by a unique pattern of anti-liver and anti-brain
      antibodies that recognized, among others, a protein of approximately 90 kDa.
      Subsequent immunoblotting showed that sera from the coexposed mice contained
      antibodies specific for heat shock proteins, a chaperone protein targeted by
      antibodies in patients with AIH. Thus, although TCE can promote autoimmune
      disease following chronic exposure, a shorter exposure to a binary mixture of TCE
      and HgCl(2) accelerated disease development. Coexposure to TCE and HgCl(2) also
      generated a unique liver-specific antibody response not found in mice exposed to
      a single toxicant. This finding stresses the importance of including mixtures in
      assessments of chemical immunotoxicity.

PMID- 21084433
TI  - Polymorphisms of eNOS gene are associated with diabetic nephropathy: a meta
      analysis.
AB  - The aim of the current study is to assess the association between the alleles of
      endothelial nitric oxide synthases (eNOS) gene 4b/a, G894T, T786C polymorphisms
      and diabetic nephropathy (DN) through meta-analyses. We also performed a subgroup
      analysis based on ethnicity (Caucasians, East-Asian and other populations). A
      total of 3793 patients (DN) and 3161 controls (diabetes without nephropathy) for
      4b/a, 2654 patients and 1993 controls for G894T and 1348 patients and 1175
      controls for T786C were included in our analysis. Overall, allele contrast (4a
      versus 4b) of 4b/a polymorphism produced significant results in the global
      population [random effects model (RE) odds ratio (OR) = 1.33; 95% confidence
      interval (CI) = 1.10-1.61, P = 0.003] and East-Asian population (RE OR = 1.68;
      95% CI = 1.23-2.30, P = 0.001), but not in the Caucasian population. In allele
      contrast of G894T, an obvious significant result was observed in the East-Asian
      population [fixed effects model OR = 1.69; 95% CI = 1.37-2.08, P < 0.0001], but
      not in the Caucasian population. Sensitivity analyses generated similar results
      to those of the primary analyses. The evidence accumulated suggested that 4b/a
      and G894T polymorphisms in the eNOS gene were associated with susceptibility to
      DN in Asian populations, but not in Caucasian populations.

PMID- 21084434
TI  - Response as a predictor of survival in patients with recurrent glioblastoma
      treated with bevacizumab.
AB  - Development of effective therapies for recurrent glioblastoma multiforme (GBM)
      and reliable, timely evaluation of their benefit are needed. Understanding the
      relationship between objective response (OR) and survival is important for
      determining whether OR can provide an early signal of treatment activity in
      clinical trials. We performed a landmark analysis to evaluate the association
      between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent
      GBM who participated in BRAIN, a phase II trial that evaluated efficacy of
      bevacizumab alone or in combination with irinotecan, using the Cox regression
      models adjusted for age, baseline Karnofsky performance score, first vs second
      relapse, and treatment arm. Hazard ratios (HRs) and P-values for survival between
      responders and nonresponders were calculated. Additional analyses were performed
      to test robustness, validity, fit, and accuracy of the models. The relationships
      between progression-free survival (PFS) and survival and between OR and PFS were
      also explored. There were 55 responders and 112 nonresponders across the 2
      treatment arms in BRAIN. OR status at 9, 18, and 26 weeks was a statistically
      significant predictor of survival (HR <= 0.52, P < .01). PFS was also a
      statistically significant predictor of survival at each landmark (HR <= 0.25, P <
      .0001). The association between OR and PFS was not statistically significant,
      likely due to inadequate statistical power for the analysis. Clarifying the
      relationship of OR and survival is important for determining whether OR can be a
      reliable predictor of the benefit of a therapeutic agent in patients with
      recurrent GBM.

PMID- 21084435
TI  - Manipulation of photoprotection to improve plant photosynthesis.

PMID- 21084436
TI  - Toxicity, response rates and survival outcomes of induction cisplatin and
      irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy for
      locally advanced esophageal cancer.
AB  - OBJECTIVE: Cisplatin-based chemoradiotherapy is standard treatment for locally
      advanced esophageal and gastroesophageal cancers; however, the optimal
      chemotherapy regimen remains to be defined. METHODS: Retrospective single
      institution analysis of toxicities, response rates and survival outcomes in
      patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated
      with induction cisplatin and irinotecan followed by concurrent cisplatin,
      irinotecan and radiotherapy. Secondary analysis for association of disease
      control and outcomes with demographic, tumor and treatment factors (including
      histology). RESULTS: Fifty-three patients were eligible for the present analysis.
      All patients underwent endoscopic ultrasonography and were either cT3-4 and/or
      cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4
      Gy, range 0-61.2), and 35 patients completed four cycles of chemotherapy as
      planned (range 1-4). Severe acute toxicities included Grade >= 3 neutropenia and
      esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal)
      toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7-63), 17
      patients were alive (8 without disease) and 36 deceased. Forty patients
      experienced disease recurrence, with initial loco-regional, distant or both
      failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival
      and freedom from failure were 42 and 9%, respectively, without significant
      difference by histology. CONCLUSIONS: Cisplatin/irinotecan chemoradiotherapy is
      tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma
      esophageal cancers.

PMID- 21084437
TI  - Does 1 year adjuvant chemotherapy with oral 5-FUs in colon cancer reduce the peak
      of recurrence in 1 year and provide long-term OS benefit?
AB  - The objective of our study was to clarify the characteristics of survival and
      hazard function in patients who received adjuvant chemotherapy after surgery for
      colon cancer. The data of 2848 patients with curatively resected colon cancer
      were analyzed; we used the patient data provided by the Japanese Foundation for
      Multidisciplinary Treatment for Cancer in three trials, namely, JFMC7-1 (n =
      869), JFMC7-2 (n = 978) and JFMC15 (n = 1001). The total number of events were
      605 (overall survival) and 724 (disease-free survival). The disease-free survival
      events consisted of 117 cases of death and 607 cases of disease recurrences.
      Logrank test showed a borderline significant difference in both overall survival
      (P = 0.0452) and disease-free survival (P = 0.0462). The 5 year overall survival
      proportion was 0.769 (control) and 0.802 (treated), and the absolute drug effect
      was 3.3%. The difference between the 5 year disease-free survival proportion
      (0.728 [control] and 0.760 [drug]) was 3.2%, which is almost similar to the
      result of overall survival. The disease-free survival curve of the treated group
      differed from that of the control group after 1 year, whereas the overall
      survival curve of the treated group became distinct from that of the control
      group after 2 years. The hazard rate plots indicated the possibility that 1 year
      adjuvant chemotherapy with oral 5-fluorouracils may translate the short-term
      reduction in the risk of recurrence in patients with resected colon cancer into a
      delayed advantage in overall survival.

PMID- 21084439
TI  - Low rates of p24 antigen detection using a fourth-generation point of care HIV
      test.

PMID- 21084438
TI  - Comparing expectations and experiences of care for sexually transmitted
      infections in general practice: a qualitative study.
AB  - BACKGROUND: A key aim of England's National Strategy for Sexual Health is to
      extend high-quality sexual health services in primary care. OBJECTIVES: To
      explore the expectations and experiences of men and women who initially presented
      at their general practice with a suspected sexually transmitted infection in
      order to identify areas where change could improve service delivery. METHODS:
      Semi-structured interviews were carried out in six general practices and two
      genitourinary medicine (GUM) clinics in Brent primary care trust (London) and
      Bristol (southwest England). Patients within general practice, and GUM patients
      who had initially attended general practice were eligible to participate.
      Interview transcripts were analysed using thematic analysis. RESULTS: 49 patients
      (29 women, 20 men) were interviewed. Patients approaching their GP practice
      typically expected written referral or in-house care, but this expectation was
      often not met. Absence of formal referral, lack of information and perceived
      avoidance of sexual health matters by practitioners were commonly cited as
      reasons for disappointment. However, a dedicated service within general practice
      met expectations well. CONCLUSION: Purchasers and providers of all general
      practice services should ensure that any patient consulting in primary care with
      a suspected sexually transmitted infection can either receive appropriate care
      there, or a formal and supported referral to a specialised GUM clinic or primary
      care service.

PMID- 21084440
TI  - The descriptive epidemiology of male sex workers in Pakistan: a biological and
      behavioural examination.
AB  - OBJECTIVES: There is a dearth of published information on the characteristics of
      sex workers in Pakistan. This study sought to characterise and compare hijra and
      non-hijra sex workers from eight large cities in Pakistan. DESIGN: chi(2) and
      Kruskal-Wallis tests, and multivariable logistic regression were used where
      appropriate. METHODS: Study respondents were described on demographic, sex-work,
      and risk behaviour variables using a cross-sectional integrated biological and
      behavioural quantitative survey. RESULTS: A total of 3350 respondents were
      surveyed, of which 2694 were included in the study. The average age of
      respondents was 24.1 years (SD 6.3), and the average duration of sex work was 7.5
      years (SD 5.9). Respondents averaged 30.9 (SD 2.7) paid receptive anal sex acts
      in the month prior to their interview, while 21.5% reported using a condom during
      their last occurrence of paid anal sex. Of those surveyed, HIV prevalence was 5.4
      per 1000; notably, no HIV-positive respondents reported any injection drug use.
      Finally, intercity heterogeneity was observed on demographic, sex work and risk
      behaviour characteristics, with almost all characteristics differing at the p <
      0.01 level. CONCLUSIONS: Low levels of education, high volume of sex acts and
      suboptimal condom use makes for a potentially volatile situation. Information
      provided by this study can play an important role in designing effective
      prevention programmes, particularly in capturing heterogeneity in sex work
      between cities, and as evidence is accumulating that a shift in epidemic phase,
      as well as affected populations is occurring in Pakistan.

PMID- 21084441
TI  - Sterol regulatory element-binding protein 2 (SREBP2) activation after excess
      triglyceride storage induces chemerin in hypertrophic adipocytes.
AB  - Chemerin is an adipokine whose systemic concentration and adipose tissue
      expression is increased in obesity. Chemerin is highly abundant in adipocytes,
      yet the molecular mechanisms mediating its further induction in obesity have not
      been clarified. Adipocyte hypertrophy contributes to dysregulated adipokine
      synthesis, and we hypothesized that excess loading with free fatty acids (FFA)
      stimulates chemerin synthesis. Chemerin was expressed in mature adipocytes, and
      differentiation of 3T3-L1 cells in the presence of FFA further increased its
      level. TNF and IL-6 were induced by FFA, but concentrations were too low to up
      regulate chemerin. Sterol regulatory element-binding protein 2 (SREBP2) was
      activated in these cells, indicative for cholesterol shortage. Suppression of
      cholesterol synthesis by lovastatin led to activation of SREBP2 and increased
      chemerin, and supplementation with mevalonate reversed this effect. Knockdown of
      SREBP2 reduced basal and FFA-induced chemerin. EMSA confirmed binding of 3T3-L1
      adipocyte nuclear proteins to a SREBP site in the chemerin promotor. SREBP2 was
      activated and chemerin was induced in adipose tissue of mice fed a high-fat diet,
      and higher systemic levels seem to be derived from adipocytes. Lipopolysaccharide
      mediated elevation of chemerin was similarly effective as induction by FFA,
      indicating that both mechanisms are equally important. Chemokine-like receptor 1
      was not altered by the incubations mentioned above, and higher expression in fat
      of mice fed a high-fat diet may reflect increased number of adipose tissue
      resident macrophages in obesity. In conclusion, the current data show that
      adipocyte hypertrophy and chronic inflammation are equally important in inducing
      chemerin synthesis.

PMID- 21084442
TI  - Effect of insulin and dexamethasone on fetal assimilation of maternal glucose.
AB  - The growing fetus depends upon transfer of glucose from maternal blood to fetal
      tissues. Insulin and glucocorticoid impact maternal glucose metabolism, but the
      effects of these hormones on fetal glucose assimilation in vivo are understudied.
      We thus used positron emission tomography imaging to determine the disposition of
      [(18)F]fluorodeoxyglucose (FDG) in rats on gestational d 20, quantifying the
      kinetic competition of maternal tissues and fetus for glucose. Three fasting
      maternal states were studied: after 2-d dexamethasone (DEX), during euglycemic
      hyperinsulinemic clamp insulin receiving (INS), and control (CON). In CON and DEX
      mothers, FDG accumulation in fetuses and placentae was substantial, rivaling that
      of maternal brain. By contrast, FDG accumulation was reduced in INS fetuses,
      placentae, and maternal brain by approximately 2-fold, despite no diminution in
      FDG extraction kinetics from maternal blood into these structures. The reduced
      FDG accumulation was due to more rapid clearance of FDG from the circulation in
      INS mothers, related to increased FDG avidity in INS select maternal tissues,
      including skeletal muscle, brown adipose tissue, and heart. DEX treatment of
      mothers reduced fetal weight by nearly 10%. Nonetheless, the accumulation of FDG
      into placentae and fetuses was similar in DEX and CON mothers. In our rat model,
      fetal growth restriction induced by DEX does not involve diminished glucose
      transport to the fetus. Maternal insulin action has little effect on the inherent
      avidity of the fetal-placental unit for glucose but increases glucose utilization
      by maternal tissues, thus indirectly reducing the glucose available to the fetus.

PMID- 21084443
TI  - Plasticity of the reproductive axis caused by social status change in an african
      cichlid fish: II. testicular gene expression and spermatogenesis.
AB  - Reproduction in all vertebrates is controlled by the brain-pituitary-gonad (BPG)
      axis, which is regulated socially in males of the African cichlid fish
      Astatotilapia burtoni. Although social information influences GnRH1 neurons at
      the apex of the BPG axis, little is known about how the social environment and
      dominance affects the cellular and molecular composition of the testes to
      regulate reproductive capacity. We created an opportunity for reproductively
      suppressed males to ascend in status and then measured changes in gene expression
      and tissue morphology to discover how quickly the perception of this opportunity
      can influence the testes. Our results show rapid up-regulation of mRNA levels of
      FSH receptor and several steroid receptor subtypes in the testes during social
      ascent. In contrast, LH receptor was not elevated until 72 h after ascent, but
      this increase was coincident with elevated circulating androgens and early stages
      of spermatogenesis, suggesting a role in steroidogenesis. The spermatogenic
      potential of the testes, as measured by cellular composition, was also elevated
      before the overall increase in testes size. The presence of cysts at all stages
      of spermatogenesis, coupled with lower levels of gonadotropin and steroid
      receptors in subordinate males, suggests that the BPG axis and spermatogenesis
      are maintained at a subthreshold level in anticipation of the chance to gain a
      territory and become reproductively active. Our results show that the testis is
      stimulated extremely quickly after perception of social opportunity, presumably
      to allow suppressed males to rapidly achieve high reproductive success in a
      dynamic social environment.

PMID- 21084445
TI  - Minireview: fibroblast growth factor 23 in phosphate homeostasis and bone
      metabolism.
AB  - Fibroblast growth factor 23 (FGF23) was identified in 2000. Since then, FGF23 has
      been found to physiologically regulate phosphate metabolism and aberrant actions
      of FGF23 results in several disorders of phosphate and bone metabolism. In
      addition, FGF23 plays an important role in the development of chronic kidney
      disease-mineral and bone disorder. However, further investigations are necessary,
      especially with regard to the regulation of FGF23 expression. In this minireview,
      we focus on the physiological and pathophysiological significance of FGF23 in
      phosphate and bone metabolism.

PMID- 21084444
TI  - The role of GH and IGF-I in mediating anabolic effects of testosterone on
      androgen-responsive muscle.
AB  - Testosterone (T) supplementation increases skeletal muscle mass, circulating GH,
      IGF-I, and im IGF-I expression, but the role of GH and IGF-I in mediating T's
      effects on the skeletal muscle remains poorly understood. Here, we show that T
      administration increased body weight and the mass of the androgen-dependent
      levator ani muscle in hypophysectomized as well as castrated plus
      hypophysectomized adult male rats. T stimulated the proliferation of primary
      human skeletal muscle cells (hSKMCs) in vitro, an effect blocked by transfecting
      hSKMCs with small interference RNA targeting human IGF-I receptor (IGF-IR). In
      differentiation conditions, T promoted the fusion of hSKMCs into larger myotubes,
      an effect attenuated by small interference RNA targeting human IGF-IR. Notably,
      MKR mice, which express a dominant negative form of the IGF-IR in skeletal muscle
      fibers, treated with a GnRH antagonist (acyline) to suppress endogenous T,
      responded to T administration by an attenuated increase in the levator ani muscle
      mass. In conclusion, circulating GH and IGF-I are not essential for mediating T's
      effects on an androgen-responsive skeletal muscle. IGF-I signaling plays an
      important role in mediating T's effects on skeletal muscle progenitor cell growth
      and differentiation in vitro. However, IGF-IR signaling in skeletal muscle fibers
      does not appear to be obligatory for mediating the anabolic effects of T on the
      mass of androgen-responsive skeletal muscles in mice.

PMID- 21084446
TI  - Targeted inactivation of the androgen receptor gene in murine proximal epididymis
      causes epithelial hypotrophy and obstructive azoospermia.
AB  - The epithelial lining of the epididymal duct expresses the androgen receptor (Ar)
      along its entire length and undergoes rapid and profound degeneration when
      androgenic support is withdrawn. However, experiments involving orchidectomy with
      systemic testosterone replacement, and testicular efferent duct ligation, have
      indicated that structural and functional integrity of the initial segment cannot
      be maintained by circulating androgen alone, leaving the role of androgen in this
      epididymal zone unclear. We addressed this question in a mouse model with intact
      testicular output and selective Ar inactivation in the proximal epididymis by
      creating double-transgenic males carrying a conditional Ar(loxP) allele and
      expressing Cre recombinase under the promoter of Rnase10, a gene specifically
      expressed in proximal epididymis. At 20-25 d of life, on the onset of Rnase10
      expression, Ar became selectively inactivated in the principal cells of proximal
      epididymis, resulting in epithelial hypoplasia and hypotrophy. Upon the
      subsequent onset of spermiation, epididymal obstruction ensued, with the
      consequent development of spermatic granulomata, back pressure-induced atrophy of
      the seminiferous epithelium, orchitis, and fibrosis of the testicular parenchyma.
      Consistent with these findings, the mice were infertile. When the effect of Ar
      knockout on gene expression in the proximal epididymis was compared with that of
      efferent duct ligation and orchidectomy, we identified genes specifically
      regulated by androgen, testicular efferent fluid, and both. Our findings
      demonstrate that the development and function of the epididymal initial segment
      is critically dependent on direct androgen regulation. The phenotype of the
      produced knockout mouse provides a novel model for obstructive azoospermia.

PMID- 21084448
TI  - Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone:
      potential implications for the treatment of metabolic syndrome.
AB  - The mineralocorticoid receptor (MR) mediates aldosterone- and glucocorticoid
      induced adipocyte differentiation. Drospirenone (DRSP) is a potent synthetic
      antimineralocorticoid with progestogenic and antiandrogenic properties, which is
      widely used for contraception and hormone replacement therapy. We investigated
      its potential role on adipocyte differentiation. The effects of DRSP were studied
      in murine preadipocyte cell lines and primary cultures of human preadipocytes.
      Differentiation markers and mechanisms underlying phenotypic variations in
      response to DRSP were explored. Early exposure to DRSP during differentiation led
      to a marked dose-dependent inhibition of adipose differentiation and triglyceride
      accumulation in 3T3-L1 and 3T3-F442A cells. DRSP also markedly inhibited adipose
      conversion of human primary preadipocytes derived from visceral (mesenteric and
      epicardial) and subcutaneous fat. This effect was MR-dependent and did not
      involve the glucocorticoid, androgen, or progesterone receptors. DRSP inhibited
      clonal expansion of preadipocytes and decreased expression of PPARgamma, a key
      transcriptional mediator of adipogenesis, but had no effect on lipolysis, glucose
      uptake, and PPARgamma binding to its ligands. DRSP exerts a potent antiadipogenic
      effect that is related to an alteration of the transcriptional control of
      adipogenesis via an antagonistic effect on the MR. Selective MR blockade
      therefore has promise as a novel therapeutic option for the control of excessive
      adipose tissue deposition and its related metabolic complications.

PMID- 21084447
TI  - Gene expression profiling reveals Cyp26b1 to be an activin regulated gene
      involved in ovarian granulosa cell proliferation.
AB  - Activin, a member of the TGF-beta superfamily, is an important modulator of FSH
      synthesis and secretion and is involved in reproductive dysfunctions and cancers.
      It also regulates ovarian follicle development. To understand the mechanisms and
      pathways by which activin regulates follicle function, we performed a microarray
      study and identified 240 activin regulated genes in mouse granulosa cells. The
      gene most strongly inhibited by activin was Cyp26b1, which encodes a P450
      cytochrome enzyme that degrades retinoic acid (RA). Cyp26b1 has been shown to
      play an important role in male germ cell meiosis, but its expression is largely
      lost in the ovary around embryonic d 12.5. This study demonstrated that Cyp26b1
      mRNA was expressed in granulosa cells of follicles at all postnatal developmental
      stages. A striking inverse spatial and temporal correlation between Cyp26b1 and
      activin-betaA mRNA expression was observed. Cyp26b1 expression was also elevated
      in a transgenic mouse model that has decreased activin expression. The Cyp26
      inhibitor R115866 stimulated the proliferation of primary cultured mouse
      granulosa cells, and a similar effect was observed with RA and activin. A pan-RA
      receptor inhibitor, AGN194310, abolished the stimulatory effect of either RA or
      activin on granulosa cell proliferation, indicating an involvement of RA receptor
      mediated signaling. Overall, this study provides new insights into the mechanisms
      of activin action in the ovary. We conclude that Cyp26b1 is expressed in the
      postnatal mouse ovary, regulated by activin, and involved in the control of
      granulosa cell proliferation.

PMID- 21084449
TI  - FOXL2 and BMP2 act cooperatively to regulate follistatin gene expression during
      ovarian development.
AB  - Follistatin is a secreted glycoprotein required for female sex determination and
      early ovarian development, but the precise mechanisms regulating follistatin
      (Fst) gene expression are not known. Here, we investigate the roles of bone
      morphogenetic protein 2 (BMP2) and forkhead-domain transcription factor L2
      (FOXL2) in the regulation of Fst expression in the developing mouse ovary. Bmp2
      and Fst showed similar temporal profiles of mRNA expression, whereas FOXL2
      protein and Fst mRNA were coexpressed in the same ovarian cells. In a cell
      culture model, both FOXL2 and BMP2 up-regulated Fst expression. In ex vivo mouse
      fetal gonad culture, exogenous BMP2 increased Fst expression, but this effect was
      counteracted by the BMP antagonist Noggin. Moreover, in Foxl2-null mice, Fst
      expression was reduced throughout fetal ovarian development, and Bmp2 expression
      was also reduced. Our data support a model in which FOXL2 and BMP2 cooperate to
      ensure correct expression of Fst in the developing ovary. Further, Wnt4-knockout
      mice showed reduced expression of Fst limited to early ovarian development,
      suggesting a role for WNT4 in the initiation, but not the maintenance, of Fst
      expression.

PMID- 21084450
TI  - GH-dependent STAT5 signaling plays an important role in hepatic lipid metabolism.
AB  - GH deficiency is known to be clinically associated with a high incidence of
      nonalcoholic fatty liver disease, and this can be reversed by GH administration.
      Here we investigated the mechanistic basis for this phenomenon using engineered
      male mice lacking different signaling elements of the GH receptor, hepatic
      stat5a/b(-/-) mice and a mouse hepatoma line. We found deficient GH-dependent
      signal transducer and activator of transcription (STAT)-5 signaling correlates
      with steatosis, and through microarray analysis, quantitative PCR, and chromatin
      immunoprecipitation, identified putative targets of STAT5 signaling responsible
      for the steatosis seen on a normal diet. These targets were verified with liver
      specific stat5a/b deletion in vivo, and in vitro we show that dominant-negative
      (DN) STAT5 increases lipid uptake in a mouse hepatoma line. Because loss of STAT5
      signaling results in elevated STAT1 and STAT3 activity and intracellular lipid
      accumulation, we have used DN-STAT5a/b, DN-STAT1, constitutively active (CA)
      STAT3, or addition of oleate/palmitate in the hepatoma line to assign which of
      these apply to individual targets in STAT5 signaling deficiency. These findings
      and published mouse models of steatosis enable us to propose elevated cd36,
      ppargamma, and pgc1alpha/beta expression as primary instigators of the steatosis
      along with elevated fatty acid synthase, lipoprotein lipase, and very low-density
      lipoprotein receptor expression. Decreased fgf21 and insig2 expression may also
      contribute. In conclusion, despite normal plasma free fatty acids and minimal
      obesity, absent GH activation leads to steatosis because activated STAT5 prevents
      hepatic steatosis. These results raise the possibility of low-dose GH treatment
      for nonalcoholic fatty liver disease.

PMID- 21084452
TI  - Dissociation of osteogenic and immunological effects by the selective
      glucocorticoid receptor agonist, compound A, in human bone marrow stromal cells.
AB  - Glucocorticoids (GCs) regulate various physiological processes, including bone
      remodeling. Whereas physiological amounts of GCs are required for proper human
      osteoblast differentiation, prolonged exposure to GCs leads to substantial bone
      loss in vivo predominantly by inhibiting osteoblast functions. Compound A (CpdA)
      is a novel GC receptor modulator with the potential of an improved benefit/risk
      profile. Here we tested the osteoimmunological effects of CpdA on primary human
      osteoblasts and their paracrine interactions with osteoclasts. To assess the
      antiinflammatory potential of CpdA in human bone marrow stromal cell (BMSC)
      derived osteoblasts, cells were stimulated with lipopolysaccharide and cytokine
      expression was determined. Similar to dexamethasone (DEX), CpdA profoundly
      suppressed lipopolysaccharide-induced TNF-alpha (-63%), IL-1beta (-38%), and IL-6
      (-36%) (P < 0.05) mRNA levels. Of note, CpdA failed to induce osteogenic
      differentiation of BMSCs, whereas DEX and budesonide enhanced matrix
      mineralization an d increased runt-related transcription factor 2 and alkaline
      phosphatase mRNA levels up to 5-fold in a dose-dependent manner. Interestingly,
      each substance promoted cell proliferation by 7-10% and suppressed apoptosis by
      25-30% at low concentrations and early differentiation stages, whereas high
      concentrations (1 MUm) suppressed proliferation and stimulated apoptosis in
      mature osteoblasts. Finally, CpdA did not increase the receptor activator of
      nuclear factor-kappaB ligand to osteoprotegerin mRNA ratio as compared with DEX
      and did not stimulate the formation of osteoclasts in coculture with BMSCs. In
      summary, CpdA displays dissociated osteogenic and immunological effects in human
      BMSCs that are distinct from those of conventional GCs. Whether the specific
      osteoimmunological profile of CpdA translates into a relevant in vivo effect
      needs to be further explored.

PMID- 21084451
TI  - The somatotrope as a metabolic sensor: deletion of leptin receptors causes
      obesity.
AB  - Leptin, the product of the Lep gene, reports levels of adiposity to the
      hypothalamus and other regulatory cells, including pituitary somatotropes, which
      secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers
      and function, suggesting that leptin may be important in their maintenance. This
      hypothesis was tested in a new animal model in which exon 17 of the leptin
      receptor (Lepr) protein was selectively deleted in somatotropes by Cre-loxP
      technology. Organ genotyping confirmed the recombination of the floxed LepR
      allele only in the pituitary. Deletion mutant mice showed a 72% reduction in
      pituitary cells bearing leptin receptor (LEPR)-b, a 43% reduction in LEPR
      proteins and a 60% reduction in percentages of immunopositive GH cells, which
      correlated with reduced serum GH. In mutants, LEPR expression by other pituitary
      cells was like that of normal animals. Leptin stimulated phosphorylated Signal
      transducer and activator of transcription 3 expression in somatotropes from
      normal animals but not from mutants. Pituitary weights, cell numbers, IGF-I, and
      the timing of puberty were not different from control values. Growth curves were
      normal during the first 3 months. Deletion mutant mice became approximately 30
      46% heavier than controls with age, which was attributed to an increase in fat
      mass. Serum leptin levels were either normal in younger animals or reflected the
      level of obesity in older animals. The specific ablation of the Lepr exon 17 gene
      in somatotropes resulted in GH deficiency with a consequential reduction in
      lipolytic activity normally maintained by GH and increased adiposity.

PMID- 21084455
TI  - Rapid adaptation of visual search in simulated hemianopia.
AB  - Patients with homonymous hemianopia have altered visual search patterns, but it
      is unclear how rapidly this develops and whether it reflects a strategic
      adaptation to altered perception or plastic changes to tissue damage. To study
      the temporal dynamics of adaptation alone, we used a gaze-contingent display to
      simulate left or right hemianopia in 10 healthy individuals as they performed 25
      visual search trials. Visual search was slower and less accurate in hemianopic
      than in full-field viewing. With full-field viewing, there were improvements in
      search speed, fixation density, and number of fixations over the first 9 trials,
      then stable performance. With hemianopic viewing, there was a rapid shift of
      fixation into the blind field over the first 5-7 trials, followed by continuing
      gradual improvements in completion time, number of fixations, and fixation
      density over all 25 trials. We conclude that in the first minutes after onset of
      hemianopia, there is a biphasic pattern of adaptation to altered perception: an
      early rapid qualitative change that shifts visual search into the blind side,
      followed by more gradual gains in the efficiency of using this new strategy, a
      pattern that has parallels in other studies of motor learning.

PMID- 21084454
TI  - Altered firing rates and patterns in interneurons in experimental cortical
      dysplasia.
AB  - Cortical dysplasia (CD) is associated with severe epilepsy in humans, and the in
      utero irradiation of fetal rats provides a model of this disorder. These animals
      show a selective loss of inhibitory interneurons, and the surviving interneurons
      have a reduced excitatory synaptic drive. The current study was undertaken to see
      how alterations in synaptic input would affect spontaneous firing of interneurons
      in dysplastic cortex. We recorded spontaneous action potentials and excitatory
      and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) from
      somatostatin (SST)-, parvalbumin (PV)-, and calretinin (CR)-immunoreactive (ir)
      interneurons. We found that SST- and PV-ir interneurons fired less frequently and
      with less regularity than controls. This corresponded to a relative imbalance in
      the ratio of EPSCs to IPSCs that favored inhibition. In contrast, CR-ir
      interneurons from CD showed no differences from controls in spontaneous firing or
      ratio of EPSCs to IPSCs. Additional studies demonstrated that synaptic input had
      a powerful effect on spontaneous firing in all interneurons. These findings
      demonstrate that a relative reduction in excitatory drive results in less active
      SST- and PV-ir interneurons in irradiated rats. This would further impair
      cortical inhibition in these animals and may be an important mechanism of
      epileptogenesis.

PMID- 21084453
TI  - Contributions of the PPC to online control of visually guided reaching movements
      assessed with fMRI-guided TMS.
AB  - The posterior parietal cortex (PPC) plays an important role in controlling
      voluntary movements by continuously integrating sensory information about body
      state and the environment. We tested which subregions of the PPC contribute to
      the processing of target- and body-related visual information while reaching for
      an object, using a reaching paradigm with 2 types of visual perturbation:
      displacement of the visual target and displacement of the visual feedback about
      the hand position. Initially, functional magnetic resonance imaging (fMRI) was
      used to localize putative target areas involved in online corrections of
      movements in response to perturbations. The causal contribution of these areas to
      online correction was tested in subsequent neuronavigated transcranial magnetic
      stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical
      sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the
      supramarginal gyrus for both perturbations. TMS over neighboring sites did not
      affect online control. Our results support the hypothesis that the aIPS is more
      generally involved in visually guided control of movements, independent of body
      effectors and nature of the visual information. Furthermore, they suggest that
      the human network of PPC subregions controlling goal-directed visuomotor
      processes extends more inferiorly than previously thought. Our results also point
      toward a good spatial specificity of the TMS effects.

PMID- 21084456
TI  - Studying hypertension in ocular fundus images using Hausdorff dispersion
      ordering.
AB  - Retinal arterial and vein diameters are altered in individuals at risk of
      cardiovascular events mainly due to high blood pressure. The measurement of
      retinal vessel diameters has been proved to reflect individuals' vascular health.
      Dispersion of such measures which are obtained by means of ocular fundus images
      is a major factor not usually considered in clinical research. In this paper, a
      method to evaluate if different levels of clinically relevant covariables induce
      greater dispersion in retinal arterial and vein diameters is proposed. A
      multivariate dispersion ordering, the Hausdorff dispersion order, is used to
      compare the level of dispersion in such diameters for different groups of
      patients. Our statistical conclusions show that dispersion is higher in
      individuals with long-standing hypertension and in those who need two or more
      drugs to control hypertension. Hereby, dispersion is increased in the most
      severely ill persons. However, a greater level of smoking seems to be associated
      with a lesser dispersion. Dispersion of the vessel diameters must be taken into
      account in the image analysis of retinal vessel diameters because the comparison
      between homogeneous groups will produce highly accurate results in medical
      research.

PMID- 21084457
TI  - Protein kinase Mzeta is essential for the induction and maintenance of dopamine
      induced long-term potentiation in apical CA1 dendrites.
AB  - Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of
      memory as well as for a cellular model of memory, hippocampal long-term
      potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function
      is required for the induction of the protein synthesis-dependent maintenance of
      CA1-LTP (L-LTP) through activation of the cAMP/PKA-pathway. In earlier studies we
      had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D
      aspartate (NMDA)-receptors for L-LTP. Furthermore, we have found the requirement
      of the atypical protein kinase C isoform, protein kinase Mzeta (PKMzeta) for
      conventional electrically induced L-LTP, in which PKMzeta has been identified as
      a LTP-specific plasticity-related protein (PRP) in apical CA1-dendrites. Here, we
      investigated whether the dopaminergic pathway activates PKMzeta. We found that
      application of dopamine (DA) evokes a protein synthesis-dependent LTP that
      requires synergistic NMDA-receptor activation and protein synthesis in apical CA1
      dendrites. We identified PKMzeta as a DA-induced PRP, which exerted its action at
      activated synaptic inputs by processes of synaptic tagging.

PMID- 21084458
TI  - Multilaboratory comparison of Streptococcus pneumoniae opsonophagocytic killing
      assays and their level of agreement for the determination of functional antibody
      activity in human reference sera.
AB  - Antibody-mediated killing of Streptococcus pneumoniae (pneumococcus) by
      phagocytes is an important mechanism of protection of the human host against
      pneumococcal infections. Measurement of opsonophagocytic antibodies by use of a
      standardized opsonophagocytic assay (OPA) is important for the evaluation of
      candidate vaccines and required for the licensure of new pneumococcal conjugate
      vaccine formulations. We assessed agreement among six laboratories that used
      their own optimized OPAs on a panel of 16 human reference sera for 13
      pneumococcal serotypes. Consensus titers, estimated using an analysis-of-variance
      (ANOVA) mixed-effects model, provided a common reference for assessing agreement
      among these laboratories. Agreement was evaluated in terms of assay accuracy,
      reproducibility, repeatability, precision, and bias. We also reviewed four
      acceptance criterion intervals for assessing the comparability of protocols when
      assaying the same reference sera. The precision, accuracy, and concordance
      results among laboratories and the consensus titers revealed acceptable
      agreement. The results of this study indicate that the bioassays evaluated in
      this study are robust, and the resultant OPA values are reproducible for the
      determination of functional antibody titers specific to 13 pneumococcal serotypes
      when performed by laboratories using highly standardized but not identical
      assays. The statistical methodologies employed in this study may serve as a
      template for evaluating future multilaboratory studies.

PMID- 21084459
TI  - Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns
      of the Mycobacterium tuberculosis protein TB10.4: consequences for immune
      recognition.
AB  - High-tuberculosis (TB)-burden countries are located in sub-Saharan Africa. We
      examined the frequency of human leukocyte antigen (HLA) alleles, followed by
      recombinant expression of the most frequent HLA-A alleles, i.e., HLA-A*3001 and
      HLA-A*3002, to study differences in mycobacterial peptide presentation and CD8(+)
      T-cell recognition. We screened a peptide library (9-mer peptides with an 8-amino
      acid overlap) for binding, affinity, and off-rate of the Mycobacterium
      tuberculosis-associated antigen TB10.4 and identified only three TB10.4 peptides
      with considerable binding to HLA-A*3001. In contrast, 22 peptides bound to HLA
      A*3002. This reflects a marked difference in the binding preference between the
      two alleles, with A*3002 tolerating a more promiscuous peptide-binding pattern
      and A*3001 accommodating only a very selective peptide repertoire. Subsequent
      analysis of the affinity and off-rate of the binding peptides revealed a strong
      affinity (8 nM to 7 MUM) and moderate off-rate (20 min to 3 h) for both alleles.
      Construction of HLA-A*3001 and HLA-A*3002 tetramers containing selected binding
      peptides from TB10.4, including a peptide which was shared among both alleles,
      QIMYNYPAM (TB10.4(3-11)), allowed us to enumerate epitope-specific T cells in HLA
      A*3001- and HLA-A*3002-typed patients with active TB. HLA-A*3001 and HLA-A*3002
      major histocompatibility complex-peptide complexes were recognized in individuals
      with active TB, irrespective of their homozygous HLA-A*3001 or HLA-A*3002 genetic
      background. The antigen-specific T cells exhibited the CD45RA(+) CCR7(+)
      precursor phenotype and the interleukin-7 receptor (CD127), which were different
      from the phenotype and receptor exhibited by the parental CD8(+) T-cell
      population.

PMID- 21084460
TI  - The inverse correlation between Staphylococcus aureus and Streptococcus
      pneumoniae colonization in infants is not explained by differences in serum
      antibody levels in the Generation R Study.
AB  - Colonization rates of Streptococcus pneumoniae and Staphylococcus aureus are
      inversely correlated in infants. Several studies have searched for determinants
      of this negative association. We studied the association between antipneumococcal
      antibodies with Staphylococcus aureus colonization and the association between
      antistaphylococcal antibodies with pneumococcal colonization in healthy children
      in the pneumococcal vaccine era. In the first year of life, no association
      between maternal IgG levels and colonization was seen. In addition, no
      association between the IgG and IgA levels in the child versus colonization
      status was seen.

PMID- 21084461
TI  - Sublingual administration of an adenovirus serotype 5 (Ad5)-based vaccine
      confirms Toll-like receptor agonist activity in the oral cavity and elicits
      improved mucosal and systemic cell-mediated responses against HIV antigens
      despite preexisting Ad5 immunity.
AB  - HIV/AIDS continue to devastate populations worldwide. Recent studies suggest that
      vaccines that induce beneficial immune responses in the mucosal compartment may
      improve the efficacy of HIV vaccines. Adenovirus serotype 5 (Ad5)-based vectors
      remain a promising platform for the development of effective vaccines. In an
      effort to improve the efficacy of Ad5-based vaccines, even in the presence of
      preexisting Ad5 immunity, we evaluated the potential for an Ad5-based HIV vaccine
      to induce antigen-specific immune responses following sublingual (s.l.)
      administration, a route not previously tested in regard to Ad-based vaccines.
      s.l. vaccination with an Ad5-based HIV-Gag vaccine resulted in a significant
      induction of Gag-specific cytotoxic T-lymphocyte (CTL) responses in both the
      systemic and the mucosal compartment. We also show that s.l. immunization not
      only avoided preexisting Ad5 immunity but also elicited a broad repertoire of
      antigen-specific CTL clones. Additionally, we confirm for the first time that
      oral delivery of a vaccine expressing a potent Toll-like receptor (TLR) agonist
      can stimulate innate immune responses through induction of cytokines and
      chemokines and activation of NK cells, NKT cells, and macrophages in vivo. These
      results positively correlated with improved antigen-specific CTL responses. These
      results could be achieved both in Ad5-naive mice and in mice with preexisting
      immunity to Ad5. The simplicity of the s.l. vaccination regimen coupled with
      augmentation of TLR-dependent pathways active in the oral cavity makes s.l.
      delivery a promising method for HIV vaccine development specifically, as well as
      for many other vaccine applications in general.

PMID- 21084462
TI  - Immunogenicity and reactivity of novel Mycobacterium avium subsp.
      paratuberculosis PPE MAP1152 and conserved MAP1156 proteins with sera from
      experimentally and naturally infected animals.
AB  - Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in
      ruminants. Development of genetic tools and completion of the M. avium subsp.
      paratuberculosis genome sequencing project have expanded the opportunities for
      antigen discovery. In this study, we determined the seroreactivities of two
      proteins encoded at the 5' and 3' regions of the MAP1152-MAP1156 gene cluster.
      MAP1152 encodes a PPE protein, and MAP1156 encodes a diacylglycerol
      acyltransferase involved in triglyceride metabolism and classified in the
      uncharacterized protein family UPF0089. Recombinant MAP proteins were
      overproduced and purified from Escherichia coli as maltose-binding protein (MBP)
      fusions. Immunoblotting analysis indicated that both MAP1152 and MAP1156
      displayed reactivity against sera of mice and rabbits immunized with live M.
      avium subsp. paratuberculosis cells and against samples from naturally infected
      cattle. In immunoblot assays, MAP1156 yielded a stronger positive signal than
      MAP1152 against sera from cattle with JD. An enzyme-linked immunosorbent assay
      for the recombinant proteins was developed and used to test preclassified
      positive and negative serum samples from naturally infected and noninfected
      cattle. Samples, with one exception, displayed no seroreactivity against the MBP
      LacZ fusion protein (P > 0.05), the negative-control antigen. MAP1152 displayed
      seroreactivity against all positive sera but no seroreactivity to the negative
      sera (P < 0.01). MAP1156 displayed stronger and more variable reactivity than
      MAP1152, but significant differences were observed between noninfected and
      infected cattle (P < 0.05). Otherwise, degrees of reactivity followed the same
      trend as the positive reference antigen. In conclusion, both proteins are
      immunogenic in mice and rabbits, and M. avium subsp. paratuberculosis-infected
      cattle mount a humoral response to both MAP1152 and MAP1156 cross-reactive
      epitopes. These findings have potential applications to diagnostics, vaccine
      production, and elucidation of the immunopathogenesis of JD.

PMID- 21084463
TI  - Promising multiple-epitope recombinant vaccine against foot-and-mouth disease
      virus type O in swine.
AB  - In order to develop a completely safe immunogen to replace the traditional
      inactivated vaccine, a tandem-repeat multiple-epitope recombinant vaccine against
      foot-and-mouth disease (FMD) virus (FMDV) type O was developed. It contained
      three copies each of residues 141 to 160 and 200 to 213 of VP1 of the O/China/99
      strain of FMDV coupled with a swine immunoglobulin G heavy-chain constant region
      (scIgG). The data showed that the multiple-epitope recombinant vaccine elicited
      high titers of anti-FMDV specific antibodies in swine at 30 days postvaccination
      (dpv) and conferred complete protection against a challenge with 103 50% swine
      infective doses of the O/China/99 strain. The anti-FMDV specific antibody titers
      were not significantly different between the multiple-epitope recombinant vaccine
      and the traditional vaccine (t test, P > 0.05). The number of 50% pig protective
      doses was 6.47, which is higher than the number recommended by the World
      Organization for Animal Health. The multiple-epitope recombinant vaccine resulted
      in a duration of immunity of at least 6 months. We speculate that the multiple
      epitope recombinant vaccine is a promising vaccine that may replace the
      traditional inactivated vaccine for the prevention and control of FMD in swine in
      the future.

PMID- 21084464
TI  - Differentiation between human coronaviruses NL63 and 229E using a novel double
      antibody sandwich enzyme-linked immunosorbent assay based on specific monoclonal
      antibodies.
AB  - Human coronaviruses (HCoVs) are responsible for respiratory tract infections
      ranging from common colds to severe acute respiratory syndrome. HCoV-NL63 and
      HCoV-229E are two of the four HCoVs that circulate worldwide and are close
      phylogenetic relatives. HCoV infections can lead to hospitalization of children,
      elderly individuals, and immunocompromised patients. Globally, approximately 5%
      of all upper and lower respiratory tract infections in hospitalized children are
      caused by HCoV-229E and HCoV-NL63. The latter virus has recently been associated
      with the childhood disease croup. Thus, differentiation between the two viruses
      is relevant for epidemiology studies. The aim of this study was to develop a
      double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) as a
      potential tool for identification and differentiation between HCoV-NL63 and HCoV
      229E. The nucleocapsid (N) proteins of HCoV-NL63 and HCoV-229E were expressed in
      an Escherichia coli system and used to immunize mice in order to obtain
      monoclonal antibodies (MAbs) specific for each virus. Three specific MAbs to HCoV
      NL63, one MAb specific to HCoV-229E, and four MAbs that recognized both viruses
      were obtained. After their characterization, three MAbs were selected in order to
      develop a differential DAS-ELISA. The described assay could detect up to 3 ng/ml
      of N protein and 50 50% tissue culture infective doses/ml of virus stock. No
      cross-reactivity with other human coronaviruses or closely related animal
      coronaviruses was found. The newly developed DAS-ELISA was species specific, and
      therefore, it could be considered a potential tool for detection and
      differentiation of HCoV-NL63 and HCoV-229E infections.

PMID- 21084465
TI  - Increased pulmonary tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-17A
      responses compensate for decreased gamma interferon production in anti-IL-12
      autovaccine-treated, Mycobacterium bovis BCG-vaccinated mice.
AB  - Interleukin-12 (IL-12) and IL-23 (which share a p40 subunit) are pivotal
      cytokines in the generation of protective Th1/Th17-type immune responses upon
      infection with the intracellular pathogen Mycobacterium tuberculosis. The role of
      IL-12 and IL-23 in protection conferred by the tuberculosis vaccine Mycobacterium
      bovis bacillus Calmette-Guerin (BCG) is, however, less well documented. By using
      an autovaccine approach, i.e., IL-12p70 cross-linked with ovalbumin and PADRE
      peptide formulated with the GSK proprietary adjuvant system AS02(V), we could
      specifically neutralize IL-12 while leaving the IL-23 axis intact. Neutralization
      of IL-12 before M. tuberculosis challenge rendered C57BL/6 mice highly
      susceptible, resulting in 30-fold-higher CFU in spleen and lungs and accelerated
      mortality. In contrast, neutralization of IL-12 in BCG-vaccinated mice prior to
      M. tuberculosis challenge only marginally affected vaccine-mediated protection.
      Analysis of cytokine production in spleen and lungs 3 weeks post-TB challenge by
      enzyme-linked immunosorbent assay and functional and flow cytometric assays
      showed significantly reduced mycobacterium-specific gamma interferon (IFN-gamma)
      responses in M. tuberculosis-infected and BCG-vaccinated mice that had been
      treated with the autovaccine. Purified protein derivative-induced tumor necrosis
      factor alpha (TNF-alpha), IL-6, and IL-17A levels, however, were highest in lungs
      from BCG-vaccinated/IL-12-neutralized animals, and even unstimulated lung cells
      from these mice produced significant levels of the three cytokines. Mycobacterium
      specific IL-4 and IL-5 production levels were overall very low, but IL-12
      neutralization resulted in increased concanavalin A-triggered polyclonal
      secretion of these Th2-type cytokines. These results suggest that TNF-alpha, IL
      6, and IL-17A may be more important pulmonary effector molecules of BCG-mediated
      protection than IFN-gamma in a context of IL-12 deficiency.

PMID- 21084466
TI  - Increased susceptibility of human-PrP transgenic mice to bovine spongiform
      encephalopathy infection following passage in sheep.
AB  - The risk of the transmission of ruminant transmissible spongiform encephalopathy
      (TSE) to humans was thought to be low due to the lack of association between
      sheep scrapie and the incidence of human TSE. However, a single TSE agent strain
      has been shown to cause both bovine spongiform encephalopathy (BSE) and human
      vCJD, indicating that some ruminant TSEs are transmissible to humans. While the
      transmission of cattle BSE to humans in transgenic mouse models has been
      inefficient, indicating the presence of a significant transmission barrier
      between cattle and humans, BSE has been transmitted to a number of other species.
      Here, we aimed to further investigate the human transmission barrier following
      the passage of BSE in a sheep. Following inoculation with cattle BSE, gene
      targeted transgenic mice expressing human PrP showed no clinical or pathological
      signs of TSE disease. However, following inoculation with an isolate of BSE that
      had been passaged through a sheep, TSE-associated vacuolation and proteinase K
      resistant PrP deposition were observed in mice homozygous for the codon 129
      methionine PRNP gene. This observation may be due to higher titers of the BSE
      agent in sheep or an increased susceptibility of humans to BSE prions following
      passage through a sheep. However, these data confirm that, contrary to previous
      predictions, it is possible that a sheep prion is transmissible to humans and
      that BSE from other species is a public health risk.

PMID- 21084467
TI  - The arginine clusters of the carboxy-terminal domain of the core protein of
      hepatitis B virus make pleiotropic contributions to genome replication.
AB  - The carboxy-terminal domain (CTD) of the core protein of hepatitis B virus is not
      necessary for capsid assembly. However, the CTD does contribute to encapsidation
      of pregenomic RNA (pgRNA). The contribution of the CTD to DNA synthesis is less
      clear. This is the case because some mutations within the CTD increase the
      proportion of spliced RNA to pgRNA that are encapsidated and reverse transcribed.
      The CTD contains four clusters of consecutive arginine residues. The
      contributions of the individual arginine clusters to genome replication are
      unknown. We analyzed core protein variants in which the individual arginine
      clusters were substituted with either alanine or lysine residues. We developed
      assays to analyze these variants at specific steps throughout genome replication.
      We used a replication template that was not spliced in order to study the
      replication of only pgRNA. We found that alanine substitutions caused defects at
      both early and late steps in genome replication. Lysine substitutions also caused
      defects, but primarily during later steps. These findings demonstrate that the
      CTD contributes to DNA synthesis pleiotropically and that preserving the charge
      within the CTD is not sufficient to preserve function.

PMID- 21084469
TI  - Identification of novel endogenous betaretroviruses which are transcribed in the
      bovine placenta.
AB  - Sequences of retroviral origin occupy approximately 10% of mammalian genomes.
      Various infectious endogenous retroviruses (ERVs) and functional retroviral
      elements have been reported for several mammals but not cattle. Here, we
      identified two proviruses, designated bovine endogenous retrovirus K1 (BERV-K1)
      and BERV-K2, containing full-length envelope (env) genes in the bovine genome.
      Phylogenetic analysis revealed that they belong to the genus Betaretrovirus. By
      reverse transcription (RT)-PCR, both BERV-K1 and -K2 env mRNAs were detected in
      the placenta and cultured bovine trophoblast cells. Real-time RT-PCR analysis
      using RNAs isolated from various bovine tissues revealed that BERV-K1 env mRNA
      was preferentially expressed in the placenta. Moreover, we also found the
      expression of doubly spliced transcripts, named the REBK1 and REBK2 genes. Both
      the REBK1 and REBK2 proteins have motifs for a putative nuclear localization
      signal and a nuclear export signal. REBK1 and REBK2 fused with green fluorescent
      proteins were localized mainly in the nuclei when they were expressed in bovine
      and porcine cells. In the env and 3' long terminal repeats of BERV-K1 and -K2, we
      found regulatory elements responsible for the splicing and transport of viral
      RNAs and/or translation of the env genes. Although we have not identified the
      expressed Env proteins in bovine tissues, these data suggest that both BERV-K1
      and BERV-K2 express Env proteins and that these proteins may have physiological
      functions in vivo.

PMID- 21084468
TI  - RIG-I-mediated antiviral signaling is inhibited in HIV-1 infection by a protease
      mediated sequestration of RIG-I.
AB  - The rapid induction of type I interferon (IFN) is essential for establishing
      innate antiviral responses. During infection, cytoplasmic viral RNA is sensed by
      two DExD/H box RNA helicases, RIG-I and MDA5, ultimately driving IFN production.
      Here, we demonstrate that purified genomic RNA from HIV-1 induces a RIG-I
      dependent type I IFN response. Both the dimeric and monomeric forms of HIV-1 were
      sensed by RIG-I, but not MDA5, with monomeric RNA, usually found in defective HIV
      1 particles, acting as a better inducer of IFN than dimeric RNA. However, despite
      the presence of HIV-1 RNA in the de novo infection of monocyte-derived
      macrophages, HIV-1 replication did not lead to a substantial induction of IFN
      signaling. We demonstrate the existence of an evasion mechanism based on the
      inhibition of the RIG-I sensor through the action of the HIV-1 protease (PR).
      Indeed, the ectopic expression of PR resulted in the inhibition of IFN regulatory
      factor 3 (IRF-3) phosphorylation and decreased expression of IFN and interferon
      stimulated genes. A downregulation of cytoplasmic RIG-I levels occurred in cells
      undergoing a single-cycle infection with wild-type provirus BH10 but not in cells
      transfected with a protease-deficient provirus, BH10-PR(-). Cellular
      fractionation and confocal microscopy studies revealed that RIG-I translocated
      from the cytosol to an insoluble fraction during the de novo HIV-1 infection of
      monocyte-derived macrophages, in the presence of PR. The loss of cytoplasmic RIG
      I was prevented by the lysosomal inhibitor E64, suggesting that PR targets RIG-I
      to the lysosomes. This study reveals a novel PR-dependent mechanism employed by
      HIV-1 to counteract the early IFN response to viral RNA in infected cells.

PMID- 21084470
TI  - Mapping the landscape of host-pathogen coevolution: HLA class I binding and its
      relationship with evolutionary conservation in human and viral proteins.
AB  - The high diversity of HLA binding preferences has been driven by the sequence
      diversity of short segments of relevant pathogenic proteins presented by HLA
      molecules to the immune system. To identify possible commonalities in HLA binding
      preferences, we quantify these using a novel measure termed "targeting
      efficiency," which captures the correlation between HLA-peptide binding
      affinities and the conservation of the targeted proteomic regions. Analysis of
      targeting efficiencies for 95 HLA class I alleles over thousands of human
      proteins and 52 human viruses indicates that HLA molecules preferentially target
      conserved regions in these proteomes, although the arboviral Flaviviridae are a
      notable exception where nonconserved regions are preferentially targeted by most
      alleles. HLA-A alleles and several HLA-B alleles that have maintained close
      sequence identity with chimpanzee homologues target conserved human proteins and
      DNA viruses such as Herpesviridae and Adenoviridae most efficiently, while all
      HLA-B alleles studied efficiently target RNA viruses. These patterns of host and
      pathogen specialization are both consistent with coevolutionary selection and
      functionally relevant in specific cases; for example, preferential HLA targeting
      of conserved proteomic regions is associated with improved outcomes in HIV
      infection and with protection against dengue hemorrhagic fever. Efficiency
      analysis provides a novel perspective on the coevolutionary relationship between
      HLA class I molecular diversity, self-derived peptides that shape T-cell immunity
      through ontogeny, and the broad range of viruses that subsequently engage with
      the adaptive immune response.

PMID- 21084471
TI  - Role of the vacuolar-ATPase in Sindbis virus infection.
AB  - Bafilomycin A(1) is a specific inhibitor of the vacuolar-ATPase (V-ATPase), which
      is responsible for pH homeostasis of the cell and for the acidification of
      endosomes. Bafilomycin A(1) has been commonly used as a method of inhibition of
      infection by viruses known or suspected to follow the path of receptor-mediated
      endocytosis and low-pH-mediated membrane fusion. The exact method of entry for
      Sindbis virus, the prototype alphavirus, remains undetermined. To further
      investigate the role of the V-ATPase in Sindbis virus infection, the effects of
      bafilomycin A(1) on the infection of BHK and insect cells by Sindbis virus were
      studied. Bafilomycin A(1) was found to block the expression of a virus-encoded
      reporter gene in both infection and transfection of BHK cells. The inhibitory
      effects of bafilomycin A(1) were found to be reversible. The results suggest that
      in BHK cells in the presence of bafilomycin A(1), virus RNA enters the cell and
      is translated, but replication and proper folding of the product proteins
      requires the function of the V-ATPase. Bafilomycin A(1) had no significant effect
      on the outcome of infection in insect cells.

PMID- 21084472
TI  - Minor oral lesions facilitate transmission of chronic wasting disease.
AB  - While chronic wasting disease (CWD) prion transmission, entry, and trafficking
      remain incompletely elucidated, natural exposure of the oral and/or nasal mucous
      membranes seems certain. Cervids commonly sustain minor lesions on oral mucous
      membranes that could have an impact on susceptibility to prion infection. To
      explore this potential cofactor, we studied cohorts of cervid PrP transgenic mice
      with or without superficial abrasions on the lingual mucosa to determine whether
      minor oral mucosa lesions may enhance susceptibility to CWD infections. Results
      demonstrated that minor lingual abrasions substantially facilitate CWD
      transmission, revealing a cofactor that may be significant in cervids and perhaps
      other species.

PMID- 21084473
TI  - Bacterial HA1 vaccine against pandemic H5N1 influenza virus: evidence of
      oligomerization, hemagglutination, and cross-protective immunity in ferrets.
AB  - The impending influenza virus pandemic requires global vaccination to prevent
      large-scale mortality and morbidity, but traditional influenza virus vaccine
      production is too slow for rapid responses. We have developed bacterial systems
      for expression and purification of properly folded functional hemagglutinin as a
      rapid response to emerging pandemic strains. A recombinant H5N1
      (A/Vietnam/1203/2004) hemagglutinin globular domain (HA1) was produced in
      Escherichia coli under controlled redox refolding conditions. Importantly, the
      properly folded HA1(1-320), i.e., HA1 lacking amino acids 321 to 330, contained
      >=75% functional oligomers without addition of foreign oligomerization sequence.
      Site-directed mutagenesis mapped the oligomerization signal to the HA1 N-terminal
      Ile-Cys-Ile residues at positions 3 to 5. The purified HA1 oligomers (but not
      monomers) bound fetuin and agglutinated red blood cells. Upon immunization of
      rabbits, the oligomeric HA1(1-320) elicited potent neutralizing antibodies
      against homologous and heterologous H5N1 viruses more rapidly than HA1(28-320)
      containing only monomers. Ferrets vaccinated with oligomeric HA1 (but not
      monomeric HA1 with the N terminus deleted) at 15 and 3 MUg/dose were fully
      protected from lethality and weight loss after challenge with homologous H5N1
      (A/Vietnam/1203/2004, clade 1) virus, as well as heterologous clade 2.2 H5N1
      (A/WooperSwan/Mongolia/244/2005) virus. Protection was associated with a
      significant reduction in viral loads in the nasal washes of homologous and
      heterologous virus challenged ferrets. This is the first study that describes the
      presence of an N-terminal oligomerization sequence in the globular domain of
      influenza virus hemagglutinin. Our findings suggest that functional oligomeric
      rHA1-based vaccines can be produced efficiently in bacterial systems and can be
      easily upscaled in response to a pandemic influenza virus threat.

PMID- 21084475
TI  - Sheep with scrapie and mastitis transmit infectious prions through the milk.
AB  - Prions are misfolded proteins that are infectious and naturally transmitted,
      causing a fatal neurological disease in humans and animals. Prion shedding routes
      have been shown to be modified by inflammation in excretory organs, such as the
      kidney. Here, we show that sheep with scrapie and lentiviral mastitis secrete
      prions into the milk and infect nearly 90% of naive suckling lambs. Thus,
      lentiviruses may enhance prion transmission, conceivably sustaining prion
      infections in flocks for generations. This study also indicates a risk of prion
      spread to sheep and potentially to other animals through dietary exposure to
      pooled sheep milk or milk products.

PMID- 21084476
TI  - Cloning of the Epstein-Barr virus-related rhesus lymphocryptovirus as a bacterial
      artificial chromosome: a loss-of-function mutation of the rhBARF1 immune evasion
      gene.
AB  - Rhesus macaques are naturally infected with a gammaherpesvirus which is in the
      same lymphocryptovirus (LCV) genus as and closely related to Epstein-Barr virus
      (EBV). The rhesus macaque LCV (rhLCV) contains a repertoire of genes identical to
      that of EBV, and experimental rhLCV infection of naive rhesus macaques accurately
      models acute and persistent EBV infection of humans. We cloned the LCL8664 rhLCV
      strain as a bacterial artificial chromosome to create recombinant rhLCV for
      investigation in this animal model system. A recombinant rhLCV (clone 16 rhLCV)
      carrying a mutation in the putative immune evasion gene rhBARF1 was created along
      with a rescued wild-type (rWT) rhLCV in which the rhBARF1 open reading frame
      (ORF) was repaired. The rWT rhLCV molecular clone demonstrated viral replication
      and B-cell immortalization properties comparable to those of the naturally
      derived LCL8664 rhLCV. Qualitatively, clone 16 rhLCV carrying a mutated rhBARF1
      was competent for viral replication and B-cell immortalization, but quantitative
      assays showed that clone 16 rhLCV immortalized B cells less efficiently than
      LCL8664 and rWT rhLCV. Functional studies showed that rhBARF1 could block CSF-1
      cytokine signaling as well as EBV BARF1, whereas the truncated rhBARF1 from clone
      16 rhLCV was a loss-of-function mutant. These recombinant rhLCV can be used in
      the rhesus macaque animal model system to better understand how a putative viral
      immune evasion gene contributes to the pathogenesis of acute and persistent EBV
      infection. The development of a genetic system for making recombinant rhLCV
      constitutes a major advance in the study of EBV pathogenesis in the rhesus
      macaque animal model.

PMID- 21084477
TI  - Early events in retrovirus XMRV infection of the wild-derived mouse Mus pahari.
AB  - A novel gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV),
      has been identified in patients with prostate cancer and in patients with chronic
      fatigue syndromes. Standard Mus musculus laboratory mice lack a functional XPR1
      receptor for XMRV and are therefore not a suitable model for the virus. In
      contrast, Gairdner's shrew-mice (Mus pahari) do express functional XPR1. To
      determine whether Mus pahari could serve as a model for XMRV, primary Mus pahari
      fibroblasts and mice were infected with cell-free XMRV. Infection of cells in
      vitro resulted in XMRV Gag expression and the production of XMRV virions. After
      intraperitoneal injection of XMRV into Mus pahari mice, XMRV proviral DNA could
      be detected in spleen, blood, and brain. Intravenous administration of a green
      fluorescent protein (GFP) vector pseudotyped with XMRV produced GFP(+) CD4(+) T
      cells and CD19(+) B cells. Mice mounted adaptive immune responses against XMRV,
      as evidenced by the production of neutralizing and Env- and Gag-specific
      antibodies. Prominent G-to-A hypermutations were also found in viral genomes
      isolated from the spleen, suggesting intracellular restriction of XMRV infection
      by APOBEC3 in vivo. These data demonstrate infection of Mus pahari by XMRV,
      potential cell tropism of the virus, and immunological and intracellular
      restriction of virus infection in vivo. These data support the use of Mus pahari
      as a model for XMRV pathogenesis and as a platform for vaccine and drug
      development against this potential human pathogen.

PMID- 21084474
TI  - Viral serine/threonine protein kinases.
AB  - Phosphorylation represents one the most abundant and important posttranslational
      modifications of proteins, including viral proteins. Virus-encoded
      serine/threonine protein kinases appear to be a feature that is unique to large
      DNA viruses. Although the importance of these kinases for virus replication in
      cell culture is variable, they invariably play important roles in virus
      virulence. The current review provides an overview of the different viral
      serine/threonine protein kinases of several large DNA viruses and discusses their
      function, importance, and potential as antiviral drug targets.

PMID- 21084478
TI  - Epitope mapping of HIV-specific CD8+ T cell responses by multiple immunological
      readouts reveals distinct specificities defined by function.
AB  - The limited success of HIV vaccine candidates to date highlights our need to
      better characterize protective cell-mediated immunity (CMI). While HIV-specific
      CD8(+) T cell responses have been defined largely by measuring gamma interferon
      (IFN-gamma), these responses are not always protective, and it is unclear whether
      the same epitopes would predominate if other functional parameters were examined.
      Here, we assessed the epitope specificity of HIV-specific CD8(+) T cell responses
      by multiparametric flow cytometry, measuring five CD8(+) T cell functions (IFN
      gamma, macrophage inflammatory protein 1beta [MIP-1beta], tumor necrosis factor
      alpha [TNF-alpha], interleukin-2 [IL-2], and proliferative capacity) in 24
      chronically HIV-infected individuals. Sixty-nine epitope-specific responses to 50
      epitopes within p24 were measured. Surprisingly, most epitope-specific responses
      were IFN-gamma negative (50/69 responses). Many responses had polyfunctional
      (33%) and proliferative (19%) components. An inverse association between IL-2 and
      proliferation responses was also observed, contrary to what was described
      previously. We confirm that long-term nonprogressors (LTNP) have more
      polyfunctional responses and also have higher-magnitude and broader p24-specific
      proliferation and higher levels of IL-2 and TNF-alpha production than do
      progressing controls. Together, these data suggest that the specificity of CD8(+)
      T cell responses differs depending on the immunological readout, with a 3.5-fold
      increase in breadth detected by including multiple parameters. Furthermore, the
      identification of epitopes that elicit polyfunctional responses reinforces the
      need for the comprehensive evaluation of HIV vaccine candidates, and these
      epitopes may represent novel targets for CMI-based vaccines.

PMID- 21084479
TI  - The nuclear and adherent junction complex component protein ubinuclein negatively
      regulates the productive cycle of Epstein-Barr virus in epithelial cells.
AB  - The Epstein-Barr Virus (EBV) productive cycle is initiated by the expression of
      the viral trans-activator EB1 (also called Zebra, Zta, or BZLF1), which belongs
      to the basic leucine zipper transcription factor family. We have previously
      identified the cellular NACos (nuclear and adherent junction complex components)
      protein ubinuclein (Ubn-1) as a partner for EB1, but the function of this complex
      has never been studied. Here, we have evaluated the consequences of this
      interaction on the EBV productive cycle and find that Ubn-1 overexpression
      represses the EBV productive cycle whereas Ubn-1 downregulation by short hairpin
      RNA (shRNA) increases virus production. By a chromatin immunoprecipitation (ChIP)
      assay, we show that Ubn-1 blocks EB1-DNA interaction. We also show that in
      epithelial cells, relocalization and sequestration of Ubn-1 to the tight
      junctions of nondividing cells allow increased activation of the productive
      cycle. We propose a model in which Ubn-1 is a modulator of the EBV productive
      cycle: in proliferating epithelial cells, Ubn-1 is nuclear and inhibits
      activation of the productive cycle, whereas in differentiated cells, Ubn-1 is
      sequestrated to tight junctions, thereby allowing EB1 to fully function in the
      nucleus.

PMID- 21084480
TI  - Functional analysis of a novel motif conserved across geminivirus Rep proteins.
AB  - Members of the Geminiviridae have single-stranded DNA genomes that replicate in
      nuclei of infected plant cells. All geminiviruses encode a conserved protein
      (Rep) that catalyzes initiation of rolling-circle replication. Earlier studies
      showed that three conserved motifs-motifs I, II, and III-in the N termini of
      geminivirus Rep proteins are essential for function. In this study, we identified
      a fourth sequence, designated GRS (geminivirus Rep sequence), in the Rep N
      terminus that displays high amino acid sequence conservation across all
      geminivirus genera. Using the Rep protein of Tomato golden mosaic virus (TGMV
      AL1), we show that GRS mutants are not infectious in plants and do not support
      viral genome replication in tobacco protoplasts. GRS mutants are competent for
      protein-protein interactions and for both double- and single-stranded DNA
      binding, indicating that the mutations did not impair its global conformation. In
      contrast, GRS mutants are unable to specifically cleave single-stranded DNA,
      which is required to initiate rolling-circle replication. Interestingly, the Rep
      proteins of phytoplasmal and algal plasmids also contain GRS-related sequences.
      Modeling of the TGMV AL1 N terminus suggested that GRS mutations alter the
      relative positioning of motif II, which coordinates metal ions, and motif III,
      which contains the tyrosine involved in DNA cleavage. Together, these results
      established that the GRS is a conserved, essential motif characteristic of an
      ancient lineage of rolling-circle initiators and support the idea that
      geminiviruses may have evolved from plasmids associated with phytoplasma or
      algae.

PMID- 21084481
TI  - Pandemic swine-origin H1N1 influenza A virus isolates show heterogeneous
      virulence in macaques.
AB  - The first influenza pandemic of the new millennium was caused by a newly emerged
      swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized by a
      previously unknown constellation of gene segments derived from North American and
      Eurasian swine lineages and the absence of common markers predictive of human
      adaptation. Overall, human infections appeared to be mild, but an alarming number
      of young individuals presented with symptoms atypical for seasonal influenza. The
      new SOIV also showed a sustained human-to-human transmissibility and higher
      reproduction ratio than common seasonal viruses, altogether indicating a higher
      pathogenic potential for this newly emerged virus. To study the virulence of the
      SOIV, we used a recently established cynomolgus macaque model and compared
      parameters of clinical disease, virology, host responses, and
      pathology/histopathology with a current seasonal H1N1 virus. We here show that
      infection of macaques with two genetically similar but clinically distinct SOIV
      isolates from the early stage of the pandemic (A/Mexico/4108/2009 and
      A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections
      and clinical disease ranging from mild to severe pneumonia that was clearly
      advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current
      seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV
      isolates in virus replication, host transcriptional and cytokine responses, and
      disease progression, demonstrating a higher pathogenic potential for
      A/Mexico/InDRE4487/2009. Differences in virulence may explain more severe
      disease, as was seen with certain individuals infected with the emerged pandemic
      influenza virus. Thus, the nonhuman primate model closely mimics influenza in
      humans.

PMID- 21084482
TI  - Inhibition of calmodulin-dependent kinase kinase blocks human cytomegalovirus
      induced glycolytic activation and severely attenuates production of viral
      progeny.
AB  - Viruses depend on the host cell to provide the energy and biomolecular subunits
      necessary for production of viral progeny. We have previously reported that human
      cytomegalovirus (HCMV) infection induces dramatic changes to central carbon
      metabolism, including glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid
      biosynthesis, and nucleotide biosynthesis. Here, we explore the mechanisms
      involved in HCMV-mediated glycolytic activation. We find that HCMV virion binding
      and tegument protein delivery are insufficient for HCMV-mediated activation of
      glycolysis. Viral DNA replication and late-gene expression, however, are not
      required. To narrow down the list of cellular pathways important for HCMV
      mediated [corrected] activation of glycolysis, we utilized pharmaceutical
      inhibitors to block pathways reported to be both involved in metabolic control
      and activated by HCMV infection. We find that inhibition of calmodulin-dependent
      kinase kinase (CaMKK), but not calmodulin-dependent kinase II (CaMKII) or protein
      kinase A (PKA), blocks HCMV-mediated activation of glycolysis. HCMV infection was
      also found to target calmodulin-dependent kinase kinase 1 (CaMKK1) expression,
      increasing the levels of CaMKK1 mRNA and protein. Our results indicate that
      inhibition of CaMKK has a negligible impact on immediate-early-protein
      accumulation yet severely attenuates production of HCMV viral progeny, reduces
      expression of at least one early gene, and blocks viral DNA replication.
      Inhibition of CaMKK did not affect the glycolytic activation induced by another
      herpes virus, herpes simplex virus type 1 (HSV-1). Furthermore, inhibition of
      CaMKK had a much smaller impact on HSV-1 replication than on that of HCMV. These
      data suggest that the role of CaMKK during the viral life cycle is, in this
      regard, HCMV specific. Taken together, our results suggest that CaMKK is an
      important factor for HCMV replication and HCMV-mediated glycolytic activation.

PMID- 21084483
TI  - A single N66S mutation in the PB1-F2 protein of influenza A virus increases
      virulence by inhibiting the early interferon response in vivo.
AB  - The PB1-F2 protein of influenza A virus can contribute to viral pathogenesis of
      influenza virus strains. Of note, an N66S amino acid mutation in PB1-F2 has been
      shown to increase the pathogenesis associated with H5N1 Hong Kong/1997 and H1N1
      Brevig Mission/1918 influenza viruses. To identify the mechanism of enhanced
      immunopathology, we evaluated the host response to two isogenic viruses that
      differ by a single amino acid at position 66 of the PB1-F2 protein. Various
      components of the adaptive immune response were ruled out as factors contributing
      to pathogenesis through knockout mouse studies. Transcriptional profiling of
      lungs from PB1-F2 66S-infected mice revealed an early delay in innate immune
      responses. In particular, enhanced activation of type I interferon (IFN) pathway
      genes, including IFN-beta, RIG-I, and numerous interferon-inducible genes, was
      not observed until day 3 postinfection. The N66S mutant virus caused increased
      cellularity in the lungs, as a result of monocyte and neutrophil infiltration.
      Furthermore, numerous cytokines and chemokines related to monocyte and neutrophil
      migration and maturation were upregulated. The cellular infiltration and
      increased cytokine expression corresponded to increased PB1-F2 66S titer. These
      data suggest that PB1-F2 N66S may contribute to the delay of innate immune
      responses, allowing for unchecked viral growth and ultimately severe
      immunopathology observed in the lungs.

PMID- 21084485
TI  - Transmission of a 2009 pandemic influenza virus shows a sensitivity to
      temperature and humidity similar to that of an H3N2 seasonal strain.
AB  - In temperate regions of the world, influenza epidemics follow a highly regular
      seasonal pattern, in which activity peaks in midwinter. Consistently with this
      epidemiology, we have shown previously that the aerosol transmission of a
      seasonal H3N2 influenza virus is most efficient under cold, dry conditions. With
      the 2009 H1N1 pandemic, an exception to the standard seasonality of influenza
      developed: during 2009 in the Northern Hemisphere, an unusually high level of
      influenza virus activity over the spring and summer months was followed by a
      widespread epidemic which peaked in late October, approximately 2.5 months
      earlier than usual. Herein we show that aerosol transmission of a 2009 pandemic
      strain shows a dependence on relative humidity and temperature very similar to
      that of a seasonal H3N2 influenza virus. Our data indicate that the observed
      differences in the timings of outbreaks with regard to the seasons are most
      likely not due to intrinsic differences in transmission between the pandemic H1N1
      and seasonal H3N2 influenza viruses.

PMID- 21084484
TI  - Viral exploitation of host SOCS protein functions.
AB  - Over the past decade, a family of host proteins known as suppressors of cytokine
      signaling (SOCS) have emerged as frequent targets of viral exploitation. Under
      physiologic circumstances, SOCS proteins negatively regulate inflammatory
      signaling pathways by facilitating ubiquitination and proteosomal degradation of
      pathway machinery. Their expression is tightly regulated to prevent excessive
      inflammation while maintaining protective antipathogenic responses. Numerous
      viruses, however, have developed mechanisms to induce robust host SOCS protein
      expression following infection, essentially "hijacking" SOCS function to promote
      virus survival. To date, SOCS proteins have been shown to inhibit protective
      antiviral signaling pathways, allowing viruses to evade the host immune response,
      and to ubiquitinate viral proteins, facilitating intracellular viral trafficking
      and progeny virus assembly. Importantly, manipulation of SOCS proteins not only
      facilitates progression of the viral life cycle but also powerfully shapes the
      presentation of viral disease. SOCS proteins can define host susceptibility to
      infection, contribute to peripheral disease manifestations such as immune
      dysfunction and cancer, and even modify the efficacy of therapeutic
      interventions. Looking toward the future, it is clear that a better understanding
      of the role of SOCS proteins in viral diseases will be essential in our struggle
      to modulate and even eliminate the pathogenic effects of viruses on the host.

PMID- 21084486
TI  - Confirmation of putative HIV-1 group P in Cameroon.
AB  - We report the second human immunodeficiency virus (HIV) belonging to the new HIV
      type 1 (HIV-1) group P lineage that is closely related to the simian
      immunodeficiency virus found in gorillas. This virus was identified in an HIV
      seropositive male hospital patient in Cameroon, confirming that the group P virus
      is circulating in humans. Results from screening 1,736 HIV-seropositive specimens
      collected in Cameroon indicate that HIV-1 group P infections are rare, accounting
      for only 0.06% of HIV infections. Despite its rarity, group P shows evidence of
      adaptation to humans.

PMID- 21084487
TI  - Genetic dissection of interferon-antagonistic functions of rabies virus
      phosphoprotein: inhibition of interferon regulatory factor 3 activation is
      important for pathogenicity.
AB  - The rabies virus (RV) phosphoprotein (P) is a type I interferon (IFN) antagonist
      preventing both transcriptional induction of IFN and IFN-mediated JAK/STAT
      signaling. In addition, P is an essential cofactor of the viral polymerase and is
      required for encapsidation of viral RNA into nucleoprotein during replication. By
      site-directed mutagenesis, we have identified a domain of P required for
      efficient inhibition of IFN induction. Phosphoproteins lacking amino acids (aa)
      176 to 181, 182 to 186, or 176 to 186 were severely compromised in counteracting
      phosphorylation of IRF3 and IRF7 by TBK1 or IKKi while retaining the full
      capacity of preventing nuclear import of activated STATs and of supporting virus
      transcription and replication. Recombinant RV carrying the mutated
      phosphoproteins (the SAD DeltaInd1, SAD DeltaInd2, and SAD DeltaInd1/2 viruses)
      activated IRF3 and beta IFN (IFN-beta) transcription in infected cells but still
      blocked STAT-mediated expression of IFN-stimulated genes. Due to a somewhat
      higher transcription rate, the SAD DeltaInd1 virus activated IRF3 more
      efficiently than the SAD DeltaInd2 virus. After intracerebral injection into
      mouse brains at high doses, the SAD DeltaInd1 virus was completely apathogenic
      for wild-type (wt) mice, while the SAD DeltaInd2 virus was partially attenuated
      and caused a slower progression of lethal rabies than wt RV. Neurovirulence of
      IFN-resistant RV thus correlates with the capacity of the virus to prevent
      activation of IRF3 and IRF7.

PMID- 21084488
TI  - Human cytomegalovirus-regulated paxillin in monocytes links cellular pathogenic
      motility to the process of viral entry.
AB  - We have established that human cytomegalovirus (HCMV) infection modulates the
      biology of target primary peripheral blood monocytes, allowing HCMV to use
      monocytes as "vehicles" for its systemic spread. HCMV infection of monocytes
      results in rapid induction of phosphatidylinositol-3-kinase [PI(3)K] and NF
      kappaB activities. Integrins, which are upstream of the PI(3)K and NF-kappaB
      pathways, were shown to be involved in HCMV binding to and entry into
      fibroblasts, suggesting that receptor ligand-mediated signaling following viral
      binding to integrins on monocytes could trigger the functional changes seen in
      infected monocytes. We now show that integrin engagement and the activation of
      the integrin/Src signaling pathway are essential for the induction of HCMV
      infected monocyte motility. To investigate how integrin engagement by HCMV
      triggers monocyte motility, we examined the infected-monocyte transcriptome and
      found that the integrin/Src signaling pathway regulates the expression of
      paxillin, which is an important signal transducer in the regulation of actin
      rearrangement during cell adhesion and movement. Functionally, we observed that
      paxillin is activated via the integrin/Src signaling pathway and is required for
      monocyte motility. Because motility is intimately connected to cellular
      cytoskeletal organization, a process that is also important in viral entry, we
      investigated the role paxillin regulation plays in the process of viral entry
      into monocytes. New results confirmed that HCMV entry into target monocytes was
      significantly reduced in cells deficient in paxillin expression or the
      integrin/Src/paxillin signaling pathway. From our data, HCMV-cell interactions
      emerge as an essential trigger for the cellular changes that allow for HCMV entry
      and hematogenous dissemination.

PMID- 21084489
TI  - Indoleamine 2,3-dioxygenase mediates the antiviral effect of gamma interferon
      against hepatitis B virus in human hepatocyte-derived cells.
AB  - Alpha interferon (IFN-alpha) is an approved medication for chronic hepatitis B.
      Gamma interferon (IFN-gamma) is a key mediator of host innate and adaptive
      antiviral immunity against hepatitis B virus (HBV) infection in vivo. In an
      effort to elucidate the antiviral mechanism of these cytokines, 37 IFN-stimulated
      genes (ISGs), which are highly inducible in hepatocytes, were tested for their
      ability to inhibit HBV replication upon overexpression in human hepatoma cells.
      One ISG candidate, indoleamine 2,3-dioxygenase (IDO), an IFN-gamma-induced enzyme
      catalyzing tryptophan degradation, efficiently reduced the level of intracellular
      HBV DNA without altering the steady-state level of viral RNA. Furthermore,
      expression of an enzymatically inactive IDO mutant did not inhibit HBV
      replication, and tryptophan supplementation in culture completely restored HBV
      replication in IDO-expressing cells, indicating that the antiviral effect
      elicited by IDO is mediated by tryptophan deprivation. Interestingly, IDO
      mediated tryptophan deprivation preferentially inhibited viral protein
      translation and genome replication but did not significantly alter global
      cellular protein synthesis. Finally, tryptophan supplementation was able to
      completely restore HBV replication in IFN-gamma- but not IFN-alpha-treated cells,
      which strongly argues that IDO is the primary mediator of IFN-gamma-elicited
      antiviral response against HBV in human hepatocyte-derived cells.

PMID- 21084490
TI  - Genetic diversity of simian immunodeficiency virus encoding HIV-1 reverse
      transcriptase persists in macaques despite antiretroviral therapy.
AB  - The impact of antiretroviral therapy (ART) on the genetics of simian
      immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) populations
      has been incompletely characterized. We analyzed SIV genetic variation before,
      during, and after ART in a macaque model. Six pigtail macaques were infected with
      an SIV/HIV chimeric virus, RT-SHIV(mne), in which SIV reverse transcriptase (RT)
      was replaced by HIV-1 RT. Three animals received a short course of efavirenz
      (EFV) monotherapy before combination ART was started. All macaques received 20
      weeks of tenofovir, emtricitabine, and EFV. Plasma virus populations were
      analyzed by single-genome sequencing. Population diversity was measured by
      average pairwise difference, and changes in viral genetics were assessed by
      phylogenetic and panmixia analyses. After 20 weeks of ART, viral diversity was
      not different from pretherapy viral diversity despite more than 10,000-fold
      declines in viremia, indicating that, within this range, there is no relationship
      between diversity and plasma viremia. In two animals with consistent SIV RNA
      suppression to <15 copies/ml during ART, there was no evidence of viral
      evolution. In contrast, in the four macaques with viremias >15 copies/ml during
      therapy, there was divergence between pre- and during-ART virus populations. Drug
      resistance mutations emerged in two of these four animals, resulting in virologic
      failure in the animal with the highest level of pretherapy viremia. Taken
      together, these findings indicate that viral diversity does not decrease with
      suppressive ART, that ongoing replication occurs with viremias >15 copies/ml, and
      that in this macaque model of ART drug resistance likely emerges as a result of
      incomplete suppression and preexisting drug resistance mutations.

PMID- 21084491
TI  - HIV-1 replication in Langerhans and interstitial dendritic cells is inhibited by
      neutralizing and Fc-mediated inhibitory antibodies.
AB  - Langerhans cells (LCs) and interstitial dendritic cells (IDCs) may be among the
      first human immunodeficiency virus type 1 (HIV-1) targets after sexual
      transmission. We generated cells of these types by differentiation of purified
      CD34(+) cord blood cells. After in vitro infection with R5-tropic strains, we
      obtained similar percentages of infected cells for both dendritic cell (DC)
      subsets. Moreover, LC infection was not increased by blockage of langerin by
      antilangerin. These results indicate that, under our experimental conditions,
      there was no evidence of any preference of HIV replication in LCs versus IDCs.
      The inhibitory activity of HIV-1-specific IgAs and IgGs against HIV-1 replication
      in LCs and IDCs was analyzed. We found that neutralizing antibodies inhibit HIV-1
      infection of both DC subsets. Interestingly, HIV-1 was inhibited more efficiently
      by the IgGs than the corresponding IgA, due to an Fcgamma receptor-dependent
      mechanism. Moreover, nonneutralizing inhibitory IgGs were able to inhibit
      infection of both LCs and IDCs. These results underline the importance of HIV-1
      inhibition by the binding of the Fc part of IgGs to Fcgamma receptors and suggest
      that the induction of neutralizing and nonneutralizing inhibitory IgGs in
      addition to neutralizing IgAs at mucosal sites may contribute to protection
      against sexual transmission of HIV-1.

PMID- 21084492
TI  - Transcriptional activity of inverted terminal repeats of various human adenovirus
      serotypes.
AB  - Fifty-three human adenovirus serotypes were identified, which are divided into
      seven subgroups A, B1, B2, C, D, E and F. All types of recombinant adenoviruses
      have serotype-specific left and right inverted terminal repeats (ITRs). There is
      evidence that sequences in the ITRs of subgroup C exhibit promoter activity,
      which in turn might influence the expression of coding sequences that are in
      close proximity. We investigated whether ITRs from the complete spectrum of
      adenovirus subgroups show transcriptional activity. We found that ITRs from
      subgroups A, C and F cloned in a forward orientation display robust
      transcriptional activity in a cell-type independent manner. In the reverse
      orientation only subgroup B2 showed transcriptional activity. Unexpectedly, we
      also found that most ITRs when located upstream of a ubiquitously active promoter
      drastically reduced reporter gene expression, suggesting that ITRs may have a
      repressive activity on transcription.

PMID- 21084493
TI  - Role of the ubiquitin-proteasome system in Bombyx mori nucleopolyhedrovirus
      infection.
AB  - The ubiquitin-proteasome system plays a central role in the degradation of
      intracellular proteins and is often required for efficient virus infection.
      Homologues of ubiquitin are found in all group I nucleopolyhedroviruses (NPVs),
      but their roles in NPV infection are still unclear. This study found that the
      specific proteasome inhibitor MG-132 markedly reduced budded virus (BV)
      production and polyhedrin expression in Bombyx mori NPV (BmNPV)-infected BmN-4
      cells. Western blot analysis revealed that treatment of cells with MG-132
      resulted in delayed and/or dysregulated viral gene product expression.
      Application of MG-132 significantly reduced BV production when applied up to 12 h
      post-infection (p.i.), whereas suppression of polyhedrin expression was almost
      abolished when applied after 6 h p.i. These results suggested that proteosomal
      degradation of viral and/or host proteins is required at an early stage of
      infection for efficient polyhedrin expression. To examine further the possible
      roles of ubiquitin signalling in BmNPV infection, the baculoviral ubiquitin gene
      (v-ubi) was deleted from the BmNPV genome. Deletion of v-ubi affected neither BV
      production nor polyhedrin expression. Furthermore, Western blots also showed that
      v-UBI was not required for degradation of IE2, which is known as a target viral
      protein of the ubiquitin-proteasome system.

PMID- 21084494
TI  - A standardized comparison of commercially available prion decontamination
      reagents using the Standard Steel-Binding Assay.
AB  - Prions are comprised principally of aggregates of a misfolded host protein and
      cause fatal transmissible neurodegenerative disorders of mammals, such as variant
      Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in
      cattle. Prions pose significant public health concerns through contamination of
      blood products and surgical instruments, and can resist conventional hospital
      sterilization methods. Prion infectivity binds avidly to surgical steel and can
      efficiently transfer infectivity to a suitable host, and much research has been
      performed to achieve effective prion decontamination of metal surfaces. Here, we
      exploit the highly sensitive Standard Steel-Binding Assay (SSBA) to perform a
      direct comparison of a variety of commercially available decontamination reagents
      marketed for the removal of prions, alongside conventional sterilization methods.
      We demonstrate that the efficacy of marketed prion decontamination reagents is
      highly variable and that the SSBA is able to rapidly evaluate current and future
      decontamination reagents.

PMID- 21084495
TI  - Characterization of antibody-mediated neutralization directed against the
      hypervariable region 1 of hepatitis C virus E2 glycoprotein.
AB  - The hypervariable region 1 (HVR1) comprising the first 27 aa of E2 glycoprotein
      is a target for neutralizing antibodies against hepatitis C virus (HCV), but the
      mechanisms of this neutralization in the cell-culture-infectious genotype 2a
      strain JFH1 HCV virus (HCVcc) system are unknown. Two rabbit polyclonal sera,
      R1020 and R140, recognizing the HVR1 of the genotype 1a isolates H77c and Glasgow
      (Gla), respectively, and a Gla HVR1-specific mouse mAb AP213 have been described
      previously. However, attempts to generate of antibodies to the JFH1 HVR1 were
      unsuccessful. Therefore, this study produced chimeric JFH1 HCVcc viruses
      harbouring the H77c or Gla HVR1 to assess the reactivity of antibodies to this
      region and their effects on virus infectivity. The inter-genotypic HVR1 swap did
      not significantly affect virus infectivity. The genotype 1a HVR1-specific
      antibodies neutralized chimeric viruses in an isolate-dependent manner,
      underlining the role of HVR1 in HCV infection. The neutralizing antibodies
      reacted mainly with the C-terminal portion of HVR1, and detailed mapping
      identified A17, F20 and Q21 in the Gla HVR1 sequence and T21 (and possibly L20)
      in the corresponding H77c sequence as key epitope residues for AP213 and R140,
      and R1020, respectively. Importantly, none of the antibodies inhibited in vitro
      binding of viral envelope glycoproteins to the best-characterized HCV receptor,
      CD81, or to the glycosaminoglycan attachment factors. However, the HVR1
      antibodies were capable of post-attachment neutralization. Overall, this study
      emphasizes the role of HVR1 in HCVcc entry and provides new tools to study this
      region further in the context of complete virions.

PMID- 21084496
TI  - Establishing a new animal model for hepadnaviral infection: susceptibility of
      Chinese Marmota-species to woodchuck hepatitis virus infection.
AB  - Hepatitis B virus infection (HBV) is a major medical problem in China. The lack
      of a suitable infection model in China is recognized as an obstacle for research
      on HBV in China. Chinese Marmota-species is phylogenetically closely related to
      Marmota monax, thus, it might be suitable to serve as an animal model for HBV
      infection. Therefore, we attempted to prove the claim about the existence of
      woodchuck hepatitis virus (WHV)-like viruses in Chinese Marmota-species and to
      determine the susceptibility of these species to experimental WHV infection. In
      the present study, 653 sera from three Chinese Marmota-species, Marmota
      himalayana, Marmota baibacina and Marmota bobak, were screened for WHV-like
      viruses by serological and molecular assays. The susceptibility to WHV of three
      species was investigated by experimental infection and monitored by testing of
      anti-WHc and WHsAg by ELISA, detection of WHV DNA by PCR, and detection of WHV
      replication intermediates and antigens in liver samples. No evidence for the
      existence of a genetically closely related virus to WHV in three Chinese Marmota
      species was found by serological assays and PCR. M. himalayana was susceptible to
      WHV infection as inoculated animals became positive for anti-WHc, WHsAg and WHV
      DNA. Further, WHV replication intermediates and proteins were detected in liver
      samples. In contrast, M. baibacina remained negative for tested virological
      parameters. M. bobak species showed a limited susceptibility to WHV. Our data do
      not support early reports about WHV-like viruses in China. M. himalayana is
      suitable for the establishment of a model for hepadnaviral infection.

PMID- 21084498
TI  - An unusual alphasatellite associated with monopartite begomoviruses attenuates
      symptoms and reduces betasatellite accumulation.
AB  - The Oman strain of Tomato yellow leaf curl virus (TYLCV-OM) and its associated
      betasatellite, an isolate of Tomato leaf curl betasatellite (ToLCB), were
      previously reported from Oman. Here we report the isolation of a second,
      previously undescribed, begomovirus [Tomato leaf curl Oman virus (ToLCOMV)] and
      an alphasatellite from that same plant sample. This alphasatellite is closely
      related (90 % shared nucleotide identity) to an unusual DNA-2-type Ageratum
      yellow vein Singapore alphasatellite (AYVSGA), thus far identified only in
      Singapore. ToLCOMV was found to have a recombinant genome comprising sequences
      derived from two extant parents, TYLCV-OM, which is indigenous to Oman, and
      Papaya leaf curl virus from the Indian subcontinent. All possible combinations of
      ToLCOMV, TYLCV-OM, ToLCB and AYVSGA were used to agro-inoculate tomato and
      Nicotiana benthamiana. Infection with ToLCOMV yielded mild leaf-curl symptoms in
      both hosts; however, plants inoculated with TYLCV-OM developed more severe
      symptoms. Plants infected with ToLCB in the presence of either helper begomovirus
      resulted in more severe symptoms. Surprisingly, symptoms in N. benthamiana
      infected with the alphasatellite together with either of the helper viruses and
      the betasatellite were attenuated and betasatellite DNA accumulation was
      substantially reduced. However, in the latter plants no concomitant reduction in
      the accumulation of helper virus DNA was observed. This is the first example of
      an attenuation of begomovirus-betasatellite symptoms by this unusual class of
      alphasatellites. This observation suggests that some DNA-2 alphasatellites encode
      a pathogenicity determinant that may modulate begomovirus-betasatellite infection
      by reducing betasatellite DNA accumulation.

PMID- 21084499
TI  - Two isoforms of the protein kinase pUL97 of human cytomegalovirus are
      differentially regulated in their nuclear translocation.
AB  - The pUL97 protein kinase encoded by human cytomegalovirus is a multifunctional
      determinant of the efficiency of viral replication and phosphorylates viral as
      well as cellular substrate proteins. Here, we report that pUL97 is expressed in
      two isoforms with molecular masses of approximately 90 and 100 kDa. ORF UL97
      comprises an unusual coding strategy in that five in-frame ATG start codons are
      contained within the N-terminal 157 aa. Site-directed mutagenesis, transient
      expression of point and deletion mutants and proteomic analyses accumulated
      evidence that the formation of the large and small isoforms result from
      alternative initiation of translation, with the start points being at amino acids
      1 and 74, respectively. In vitro kinase assays demonstrated that catalytic
      activity, in terms of autophosphorylation and histone substrate phosphorylation,
      was indistinguishable for the two isoforms. An analysis of the intracellular
      distribution of pUL97 by confocal laser-scanning microscopy demonstrated that
      both isoforms have a pronounced nuclear localization. Surprisingly, mapping
      experiments performed to identify the nuclear localization signal (NLS) of pUL97
      strongly suggest that the mechanism of nuclear transport is distinct for the two
      isoforms. While the extreme N terminus (large isoform) comprises a highly
      efficient, bipartite NLS (amino acids 6-35), a second sequence apparently
      conferring a less efficient mode of nuclear translocation was identified
      downstream of amino acid 74 (small and large isoforms). Taken together, the
      findings argue for a complex mechanism of nuclear translocation for pUL97 which
      might be linked with fine-regulatory differences between the two isoforms.

PMID- 21084500
TI  - Genomic analysis of the first laboratory-mouse papillomavirus.
AB  - A papillomavirus (PV) that naturally infects laboratory mice will provide an
      extremely valuable tool for PV research. We describe here the isolation, cloning
      and molecular analysis of the first novel laboratory-mouse PV, designated MusPV.
      This agent, recently identified in the tissues from florid and asymmetrical
      papillomas on the face of nude mice (NMRI-Foxn1(nu)/Foxn1(nu)), was demonstrated
      to be transmissible to immunocompetent mice (Ingle et al., 2010). The MusPV
      genome is 7510 bp in length, is organized similarly to those of other PVs and has
      at least seven ORFs (E1, E2, E4, E6, E7, L1 and L2). Phylogenetic analysis
      indicates that MusPV belongs to the pi genus together with four other rodent PVs
      (McPV2, MaPV1, MmiPV and RnPV1). Of the rodent PVs, MusPV appears most closely
      related to Mastomys coucha PV (McPV2), with 65 % genomic homogeneity and 80 % L1
      amino acid similarity. Rodent PVs, except for MnPV1, do not contain any
      identifiable retinoblastoma protein (RB) binding sites. MusPV has one putative RB
      binding site on the E6 protein but not on the E7 protein. Non-coding regions
      (NCRs) of PVs maintain multiple binding sites for transcription factors (TFs).
      The NCR of MusPV has numerous sites for TF binding, of which at least 13 TFs are
      common to all PVs in the pi genus. MusPV provides a potentially valuable, novel
      mouse model to study mechanisms of infection, oncology and novel preventive and
      therapeutic approaches in mice that can be translated to diseases caused by human
      PVs.

PMID- 21084497
TI  - The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and
      GBV-D in genus Pegivirus within the family Flaviviridae.
AB  - In 1967, it was reported that experimental inoculation of serum from a surgeon
      (G.B.) with acute hepatitis into tamarins resulted in hepatitis. In 1995, two new
      members of the family Flaviviridae, named GBV-A and GBV-B, were identified in
      tamarins that developed hepatitis following inoculation with the 11th GB passage.
      Neither virus infects humans, and a number of GBV-A variants were identified in
      wild New World monkeys that were captured. Subsequently, a related human virus
      was identified [named GBV-C or hepatitis G virus (HGV)], and recently a more
      distantly related virus (named GBV-D) was discovered in bats. Only GBV-B, a
      second species within the genus Hepacivirus (type species hepatitis C virus), has
      been shown to cause hepatitis; it causes acute hepatitis in experimentally
      infected tamarins. The other GB viruses have however not been assigned to a genus
      within the family Flaviviridae. Based on phylogenetic relationships, genome
      organization and pathogenic features of the GB viruses, we propose to classify
      GBV-A-like viruses, GBV-C and GBV-D as members of a fourth genus in the family
      Flaviviridae, named Pegivirus (pe, persistent; g, GB or G). We also propose
      renaming 'GB' viruses within the tentative genus Pegivirus to reflect their host
      origin.

PMID- 21084501
TI  - Can we avoid "SIN" in the house of "no common mechanism"?

PMID- 21084504
TI  - Predominance of porcine P[23] genotype rotaviruses in piglets with diarrhea in
      northern Thailand.
AB  - Of 131 stool samples collected from piglets with diarrhea in northern Thailand
      between July 2006 and August 2008, 14 (10.7%) were positive for group A
      rotavirus. Sequence analysis showed that 13 strains (92.9%) belonged to the rare
      P[23] genotype combination with G9 or G3 genotypes.

PMID- 21084503
TI  - Molecular detection, epidemiology, and genetic characterization of novel European
      field isolates of equine infectious anemia virus.
AB  - The application of molecular diagnostic techniques along with nucleotide sequence
      determination to permit contemporary phylogenetic analysis of European field
      isolates of equine infectious anemia virus (EIAV) has not been widely reported.
      As a result, of extensive testing instigated following the 2006 outbreak of
      equine infectious anemia in Italy, 24 farms with a history of exposure to this
      disease were included in this study. New PCR-based methods were developed, which,
      especially in the case of DNA preparations from peripheral blood cells, showed
      excellent correlation with OIE-approved agar gel immunodiffusion (AGID) tests for
      identifying EIAV-infected animals. In contrast, the OIE-recommended
      oligonucleotide primers for EIAV failed to react with any of the Italian
      isolates. Similar results were also obtained with samples from four Romanian
      farms. In addition, for the first time complete characterization of gag genes
      from five Italian isolates and one Romanian isolate has been achieved, along with
      acquisition of extensive sequence information (86% of the total gag gene) from
      four additional EIAV isolates (one Italian and three Romanian). Furthermore, in
      another 23 cases we accomplished partial characterization of gag gene sequences
      in the region encoding the viral matrix protein. Analysis of this information
      suggested that most Italian isolates were geographically restricted, somewhat
      reminiscent of the "clades" described for human immunodeficiency virus type 1
      (HIV-1). Collectively this represents the most comprehensive genetic study of
      European EIAV isolates conducted to date.

PMID- 21084505
TI  - Extraction of Acanthamoeba DNA by use of Chelex resin.

PMID- 21084502
TI  - Polymorphisms in the intermediate region of VacA impact Helicobacter pylori
      induced disease development.
AB  - Helicobacter pylori is the etiological agent of diseases such as gastritis,
      gastric and duodenal ulcers, and two types of gastric cancers. While some insight
      has been gained into the etiology of these diverse manifestations, by and large,
      the reason that some individuals develop more severe disease remains elusive.
      Recent studies have focused on the roles of H. pylori toxins CagA and VacA on the
      disease process and have suggested that both toxins are intimately involved.
      Moreover, CagA and VacA are polymorphic within different H. pylori strains, and
      particular polymorphisms seem to show a correlation with the development of
      particular disease states. Among VacA polymorphisms, the intermediate region has
      recently been proposed to play a major role in disease outcome. In this article,
      we describe a detailed sequence analysis of the polymorphic intermediate region
      of vacA from strains obtained from a large South Korean population. We show that
      polymorphisms found at amino acid position 196 are associated with more severe
      disease manifestations. Additionally, polymorphisms found at amino acid position
      231 are linked to disease in strains that carry the non-EPIYA-ABD allele of CagA.
      Collectively, these data help explain the impact of the VacA intermediate region
      on disease and lead to the hypothesis that there are allele-driven interactions
      between VacA and CagA.

PMID- 21084506
TI  - Rapid first- and second-line drug susceptibility assay for Mycobacterium
      tuberculosis isolates by use of quantitative PCR.
AB  - The slow turnaround time for Mycobacterium tuberculosis drug susceptibility
      results is a barrier to care. We developed a rapid quantitative PCR (qPCR)-based
      phenotypic antimicrobial susceptibility test that utilizes amplification of the
      M. tuberculosis 16S rRNA gene after 3 days of incubation with antituberculosis
      drugs. To decrease background from killed organisms, we used propidium monoazide
      (PMA), a DNA-binding dye that penetrates damaged bacterial cells and renders DNA
      unamplifiable. M. tuberculosis was cultured in broth media containing PMA with or
      without drugs for 3 days prior to DNA extraction and real-time PCR amplification.
      16S rRNA qPCR exhibited a significant decrease in threshold cycle (C(T)) time
      values (C(T) control - C(T) drug treated) with drug-susceptible strains compared
      with resistant strains. Susceptibility data were reported as DeltaCT or as
      2(Delta)(CT) and with appropriate cutoffs yielded an accuracy of 89 to 100% on 38
      susceptible, multidrug-resistant, and extensively drug-resistant strains compared
      with conventional agar proportion susceptibility results for isoniazid, rifampin,
      ethambutol, streptomycin, amikacin, kanamycin, capreomycin, ofloxacin,
      moxifloxacin, ethionamide, para-aminosalicylic acid, linezolid, and cycloserine
      and compared with Bactec MGIT results for pyrazinamide. This PMA-qPCR assay is
      useful as a rapid 3-day first- and second-line drug susceptibility test for M.
      tuberculosis.

PMID- 21084508
TI  - Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of
      undetermined significance with Amplicor HPV and Hybrid Capture 2 assays for
      detection of high-grade lesions of the uterine cervix.
AB  - Up to 20% of women having a cytology smear showing atypical squamous cells of
      undetermined significance (ASC-US) and infected with high-risk human
      papillomavirus (HR HPV) have high-grade cervical intraepithelial neoplasia (CIN
      2/3). Results obtained with the Amplicor HPV and Hybrid Capture 2 (HC-2) assays
      for HR HPV DNA detection in women referred to colposcopy for an ASC-US smear were
      compared. Cervical samples in PreservCyt were tested for the presence of 13 HR
      HPV types with HC-2, with Amplicor at three cutoffs for positivity (0.2, 1.0, and
      1.5 optical density units), and for 36 genotypes with the Linear Array (LA). Of
      396 eligible women, 316 did not have CIN, 47 had CIN 1, 29 had CIN 2/3, and 4 had
      CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 164 (41.4%) samples
      with HC-2 and Amplicor HPV (cutoff, 0.2), respectively (P = 0.01). Overall, 112
      specimens were positive and 215 were negative with the HC-2 and Amplicor HPV
      assays (agreement of 82.6%; 95% confidence interval [CI], 78.5 to 86.0). The
      clinical sensitivity and specificity of Amplicor HPV at cutoffs of 0.2, 1.0 and
      1.5 and of HC-2 for detection of CIN 2/3 were 89.7% (95% CI, 72.8 to 97.2) and
      62.5% (95% CI, 57.5 to 52.4), 89.7% (95% CI, 72.8 to 97.2) and 64.5% (95% CI,
      59.4 to 69.2), 89.7% (95% CI, 72.8 to 97.2) and 64.7% (95% CI, 59.7 to 69.5), and
      93.1% (95% CI, 77.0 to 99.2) and 72.2% (95% CI, 67.4 to 76.5), respectively. Both
      HR HPV detection tests identified women with ASC-US who would benefit the most
      from colposcopy. Women with persistent HR HPV infection need further
      investigation despite a first normal colposcopy.

PMID- 21084507
TI  - Factors associated with nasal colonization of methicillin-resistant
      Staphylococcus aureus among healthy children in Taiwan.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been identified as a major
      cause of community-associated (CA) S. aureus infections in the past decade. The
      main reservoir in the community for MRSA and the factors contributing to its
      worldwide spread remain poorly defined. Between July 2005 and June 2008, a total
      of 6,057 healthy children 2 to 60 months of age were screened for carriage of S.
      aureus and Streptococcus pneumoniae in Taiwan. The prevalence and epidemiological
      factors influencing MRSA carriage were determined. MRSA strains were tested for
      antimicrobial susceptibility and underwent molecular characterization. The
      overall prevalences of MRSA and S. aureus carriage were 7.8% and 23.2%,
      respectively. A majority (88%) of MRSA isolates belonged to a common Asian
      Pacific CA-MRSA lineage, multilocus sequence type 59, and were resistant to
      multiple non-beta-lactam antibiotics. The carriage rate of MRSA was higher among
      subjects 2 to 6 months old (P < 0.0001), residing in northern Taiwan (P =
      0.0003), and enrolled later in the study (P < 0.0001). MRSA colonization was
      associated with the number of children in the family (adjusted odds ratio [aOR],
      1.114; 95% confidence interval [CI], 1.002 to 1.240; P = 0.0463) and day care
      attendance (aOR, 1.530; 95% CI, 1.201 to 1.949; P = 0.0006). Breast feeding (P <
      0.0001) and colonization with S. pneumoniae (P = 0.0170) were protective against
      MRSA colonization. We concluded that epidemic CA-MRSA strains increasingly
      colonized Taiwanese children between 2005 and 2008. The carriage rate varied
      significantly across different demographical features. Crowding was an
      independent environmental risk factor that might accelerate CA-MRSA transmission
      in the community.

PMID- 21084509
TI  - Catheter-associated Nocardia higoensis bacteremia in a child with acute
      lymphocytic leukemia.
AB  - A 23-month-old child with leukemia who was receiving chemotherapy developed
      fevers. Serial blood cultures from a central venous catheter and a peripheral
      venous site grew an organism identified by 16S rRNA gene sequencing and
      phenotypic analysis as Nocardia higoensis, an opportunistic organism isolated
      once previously from a pulmonary infection in Japan.

PMID- 21084510
TI  - Novel multiplex oligonucleotide-conjugated bead suspension array for rapid
      identification of enterovirus 71 subgenogroups.
AB  - A high-throughput multiplex bead suspension array was developed for the rapid
      subgenogrouping of EV71 strains, based on single nucleotide polymorphisms
      observed within the VP1 region with a high sensitivity as low as 1 PFU. Of 33
      viral isolates and 55 clinical samples, all EV71 strains were successfully
      detected and correctly subgenogrouped.

PMID- 21084511
TI  - Granulomatous amebic encephalitis in a child with acute lymphoblastic leukemia
      successfully treated with multimodal antimicrobial therapy and hyperbaric oxygen.
AB  - Acanthamoeba is the causative agent of granulomatous amebic encephalitis, a rare
      and usually fatal disease. We report a child with acute lymphoblastic leukemia
      who developed brain abscesses caused by Acanthamoeba during induction therapy.
      Multimodal antimicrobial chemotherapy and hyperbaric oxygen therapy resulted in
      complete resolution of symptoms and of pathology as seen by magnetic resonance
      imaging.

PMID- 21084512
TI  - Multiplexed typing of Mycobacterium avium subsp. paratuberculosis types I, II,
      and III by Luminex xMAP suspension array.
AB  - Differentiation among types I, II, and III is the primary step in typing
      Mycobacterium avium subsp. paratuberculosis. We propose an innovative approach
      based on detection of gyrase B (gyrB) gene polymorphisms by suspension array
      technology, with high discriminatory power and high-throughput potential.

PMID- 21084513
TI  - Diversity and clinical impact of Acinetobacter baumannii colonization and
      infection at a military medical center.
AB  - The epidemiology of Acinetobacter baumannii emerging in combat casualties is
      poorly understood. We analyzed 65 (54 nonreplicate) Acinetobacter isolates from
      48 patients (46 hospitalized and 2 outpatient trainees entering the military)
      from October 2004 to October 2005 for genotypic similarities, time-space
      relatedness, and antibiotic susceptibility. Clinical and surveillance cultures
      were compared by amplified fragment length polymorphism (AFLP) genomic
      fingerprinting to each other and to strains of a reference database. Antibiotic
      susceptibility was determined, and multiplex PCR was performed for OXA-23-like, 
      24-like, -51-like, and -58-like carbapenemases. Records were reviewed for
      overlapping hospital stays of the most frequent genotypes, and risk ratios were
      calculated for any association of genotype with severity of Acute Physiology and
      Chronic Health Evaluation II (APACHE II) score or injury severity score (ISS) and
      previous antibiotic use. Nineteen genotypes were identified; two predominated,
      one consistent with an emerging novel international clone and the other unique to
      our database. Both predominant genotypes were carbapenem resistant, were present
      at another hospital before patients' admission to our facility, and were
      associated with higher APACHE II scores, higher ISSs, and previous carbapenem
      antibiotics in comparison with other genotypes. One predominated in wound and
      respiratory isolates, and the other predominated in wound and skin surveillance
      samples. Several other genotypes were identified as European clones I to III.
      Acinetobacter genotypes from recruits upon entry to the military, unlike those in
      hospitalized patients, did not include carbapenem-resistant genotypes.
      Acinetobacter species isolated from battlefield casualties are diverse, including
      genotypes belonging to European clones I to III. Two carbapenem-resistant
      genotypes were epidemic, one of which appeared to belong to a novel international
      clone.

PMID- 21084514
TI  - "Mycobacterium avium subsp. hominissuis" in neck lymph nodes of children and
      their environment examined by culture and triplex quantitative real-time PCR.
AB  - "Mycobacterium avium subsp. hominissuis" often causes cervical lymphadenitis in
      children; its prompt and accurate identification enables adequate therapy,
      tracing, and prevention. The aims of this study were to determine the causative
      agent of lymphadenitis using culture, PCR, and triplex quantitative real-time PCR
      (qPCR) methods with DNA directly isolated from tissue, as well as to identify
      possible sources of infection from the environment. We confirmed the diagnoses by
      detecting M. avium subsp. hominissuis using qPCR with DNA directly isolated from
      lymph node biopsy specimens of two patients. In order to trace the source of
      infection from the environment, a method of DNA isolation from soil and other
      environmental samples, such as dust, cobwebs, and compost, was developed. The
      triplex qPCR examination revealed the presence of M. avium subsp. hominissuis in
      a high proportion of the environmental samples (42.8% in the first patient's
      house and 47.6% in the second patient's house). Both patients were also exposed
      to M. avium subsp. avium, which was present due to the breeding of infected
      domestic hens. The high infectious dose of M. avium subsp. hominissuis or the
      increased susceptibility of humans to M. avium subsp. hominissuis compared to M.
      avium subsp. avium could be the reason why the children were infected with M.
      avium subsp. hominissuis.

PMID- 21084515
TI  - Comparison of the RealTime HIV-1, COBAS TaqMan 48 v1.0, Easy Q v1.2, and Versant
      v3.0 assays for determination of HIV-1 viral loads in a cohort of Canadian
      patients with diverse HIV subtype infections.
AB  - HIV clinics in Canada provide care to an increasing number of patients born
      outside of Canada with HIV-1 non-B subtype infections. Because the Easy Q HIV-1
      v1.2 assay (EQ; bioMerieux) failed to detect some non-B subtype infections, a
      multiassay HIV-1 viral load (VL) study was conducted with patients with diverse
      HIV subtype infections. Patients were enrolled from the Southern Alberta HIV
      Clinic (SAC), Calgary, Alberta, Canada (n = 349) and the McGill HIV Clinic (MHC),
      Montreal, Quebec, Canada (n = 20) and had four or five tubes of blood drawn for
      testing by EQ and three other commercial HIV VL assays: (i) the Versant 3.0 HIV-1
      test, with the Versant 440 instrument (branched DNA [bDNA]; Siemens), (ii) the
      RealTime HIV-1 test, with the m2000rt instrument (m2000rt; Abbott Molecular
      Diagnostics), and (iii) the COBAS AmpliPrep TaqMan HIV-1 48 test (CAP-CTM; Roche
      Molecular Diagnostics). Blood was processed according to the individual
      manufacturer's requirements and stored frozen at -86 degrees C. The HIV subtype
      was known for patients who had undergone HIV genotypic resistance testing (Virco,
      Belgium). Data analyses were done using standard statistical methods within Stata
      9.0 (StataCorp, College Station, TX). A total of 371 samples were tested on 369
      patients, of whom 291 (81%) had a Virco genotype result of B (195; 53%) or non-B
      (96; 26%) subtypes A to D and F to K, as well as circulating recombinant forms
      (CRFs) (i.e., CRF01_AE and CRF02_AG). Most (58/78; 74%) patients of unknown
      subtype were recent African emigrants who likely have non-subtype B infection.
      Overall bias was small in pairwise Bland-Altman plots, but the limits of
      agreement between assays were wide. Discordant viral load results occurred for 98
      samples and were due to missing values, false negatives, and significant
      underquantification that varied by HIV subtype. Results were obtained for all 371
      samples with m2000rt, but for only 357 (97%) with CAP-CTM, 338 (92%) with EQ, and
      276 (75%) with bDNA due to errors/equipment failures. False-negative results
      (nondetection of viral RNA versus other assay results) occurred for all
      platforms, as follows: for m2000rt, 8 (2%) [B(4) and non-B(4) subtypes], CAP-CTM,
      9 (2.5%) [B(6) and non-B(3) subtypes]; EQ, 20 (6%) [B(7) and non-B(13) subtypes];
      bDNA, 5 (2%) [B(1) and C(4)]. EQ and bDNA had the highest rates of
      underquantification by >= 1.0 log(10) copies/ml, mainly for HIV non-B subtypes.
      Performance significantly varied between HIV VL platforms according to subtype.
      HIV viral diversity in the population being tested must be considered in
      selection of the viral load platform.

PMID- 21084516
TI  - Is infection by Dermatophilus congolensis underdiagnosed?
AB  - Dermatophilus congolensis, which affects animal species, is an uncommon human
      infection. Few cases, mainly in tropical areas, have been reported. We describe
      the first human infection in Spain in a traveler returning from Central America.
      Diagnosis of human infection may be underestimated in people in contact with
      animals.

PMID- 21084517
TI  - Comparison of three molecular techniques for typing Pseudomonas aeruginosa
      isolates in sputum samples from patients with cystic fibrosis.
AB  - Monitoring the emergence and transmission of Pseudomonas aeruginosa strains among
      cystic fibrosis (CF) patients is important for infection control in CF centers
      internationally. A recently developed multilocus sequence typing (MLST) scheme is
      used for epidemiologic analyses of P. aeruginosa outbreaks; however, little is
      known about its suitability for isolates from CF patients compared with that of
      pulsed-field gel electrophoresis (PFGE) and enterobacterial repetitive intergenic
      consensus-PCR (ERIC-PCR). As part of a prevalence study of P. aeruginosa strains
      in Australian CF clinics, we compared the discriminatory power and concordance of
      ERIC-PCR, PFGE, and MLST among 93 CF sputum and 11 control P. aeruginosa
      isolates. PFGE and MLST analyses were also performed on 30 paired isolates
      collected 85 to 354 days apart from 30 patients attending two CF centers
      separated by 3,600 kilometers in order to detect within-host evolution. Each of
      the three methods displayed high levels of concordance and discrimination;
      however, overall lower discrimination was seen with ERIC-PCR than with MLST and
      PFGE. Analysis of the 50 ERIC-PCR types yielded 54 PFGE types, which were related
      by <= 6 band differences, and 59 sequence types, which were classified into 7
      BURST groups and 42 singletons. MLST also proved useful for detecting novel and
      known strains and for inferring relatedness among unique PFGE types. However, 47%
      of the paired isolates produced PFGE patterns that within 1 year differed by one
      to five bands, whereas with MLST all paired isolates remained identical. MLST
      thus represents a categorical analysis tool with resolving power similar to that
      of PFGE for typing P. aeruginosa. Its focus on highly conserved housekeeping
      genes is particularly suited for long-term clinical monitoring and detecting
      novel strains.

PMID- 21084518
TI  - In vitro selection of clinically relevant bevirimat resistance mutations revealed
      by "deep" sequencing of serially passaged, quasispecies-containing recombinant
      HIV-1.
AB  - Initial in vitro studies of bevirimat resistance failed to observe mutations in
      the clinically significant QVT motif in SP1 of HIV-1 gag. This study presents a
      novel screening method involving mixed, clinically derived gag-protease
      recombinant HIV-1 samples to more accurately mimic the selection of resistance
      seen in vivo. Bevirimat resistance was investigated via population-based
      sequencing performed with a large, initially antiretroviral-naive cohort before
      (n = 805) and after (n = 355) standard HIV therapy (without bevirimat). The
      prevalence of any polymorphism in the motif comprising Q, V, and T was ~ 6%, 29%,
      and 12%, respectively, and did not change appreciably over the course of therapy.
      From these samples, three groups of 10 samples whose bulk sequences were wild
      type at the QVT motif were used to generate gag-protease recombinant viruses that
      captured the existing diversity. Groups were mixed and passaged with various
      bevirimat concentrations for 9 weeks. gag variations were assessed by amplicon
      based "deep" sequencing using a GS FLX sequencer (Roche). Unscreened mutations
      were present in all groups, and a V370A minority not originally detected by bulk
      sequencing was present in one group. V370A, occurring together with another
      preexisting, unscreened resistance mutation, was selected in all groups in the
      presence of a bevirimat concentration above 0.1 MUM. For the two groups with
      V370A levels below consistent detectability by deep sequencing, the initial
      selection of V370A required 3 to 4 weeks of exposure to a narrow range of
      bevirimat concentrations, whereas for the group with the V370A minority,
      selection occurred immediately. This approach provides quasispecies diversity
      that facilitates the selection of mutations observed in clinical trials and,
      coupled with deep sequencing, could represent an efficient in vitro screening
      method for detecting resistance mutations.

PMID- 21084519
TI  - Distinguishing acute from chronic hepatitis C virus (HCV) infection based on
      antibody reactivities to specific HCV structural and nonstructural proteins.
AB  - Currently available serological assays for detection of antibodies to hepatitis C
      virus (HCV) cannot reliably discriminate acute from chronic HCV infection. We
      developed a multiplexed, flow-cytometric microsphere immunoassay to measure anti
      HCV-IgG reactivities to the core, NS3, NS4, and NS5 HCV recombinant proteins and
      applied it to 99 serum samples from 24 anti-HCV seroconverters and 141 anti-HCV
      IgG and HCV RNA-positive plasma specimens from chronically infected people.
      Differences in the geometric means or means of signal/cutoff ratios between the
      two sample sets were statistically significant for all the antigens tested. A
      multivariate logistic regression model correctly classified the samples in two
      groups, with a cross-validation accuracy of 90.8% for the acute group and 97.2%
      for the chronic group. The immunoassay described has the potential to distinguish
      acute from chronic HCV infection.

PMID- 21084520
TI  - Association of high-level mupirocin resistance and multidrug-resistant
      methicillin-resistant Staphylococcus aureus at an academic center in the
      midwestern United States.
AB  - Mupirocin is a topical antimicrobial used to eradicate methicillin-resistant
      Staphylococcus aureus (MRSA) colonization, usually in the absence of
      susceptibility testing. We hypothesized that high-level (HL) mupirocin resistance
      was associated with multidrug resistance (MDR). To this end, unique patient
      isolates identified at our institution during 2008 were stratified into those
      resistant to >= 3 non-beta-lactam antimicrobial classes (MDR) and non-MDR MRSA.
      HL mupirocin resistance was screened by mupA PCR on all MDR isolates (n = 191)
      and a 20% random sample (n = 130) of non-MDR isolates; E-testing confirmed HL
      resistance. We found that among MDR isolates, 13 (6.8%) carried mupA, whereas
      none of the non-MDR isolates did (P = 0.001). Thus, although the overall
      prevalence of HL mupirocin resistance is low among MRSA isolates at our
      institution, an association exists between mupA carriage and MDR. Using
      genotyping and antimicrobial susceptibility profiling, we identified nine HL
      mupirocin-resistant clones. Whereas the majority of mupA-negative MDR isolates
      had a health care-associated MRSA (HA-MRSA) genotype (multilocus sequence type 5
      [ST5] or SCCmec type II), the majority of mupA-positive MDR isolates had a
      community-associated MRSA (CA-MRSA) genotype (ST8 or SCCmec type IV). However, CA
      and HA-MRSA genotypes were more evenly distributed among mupA-positive isolates
      compared to mupA-negative MDR isolates. Thus, in Chicago, mupA is circulating
      among both CA- and HA-MRSA backgrounds.

PMID- 21084521
TI  - Diversity of pulsed-field gel electrophoresis patterns of Mycobacterium abscessus
      type 2 clinical isolates.
AB  - An epidemic of infections by rapidly growing mycobacteria related to surgical
      procedures between 2004 and 2008 in Brazil was caused by a unique strain showing
      the Mycobacterium abscessus type 2 pattern when it was analyzed by the molecular
      method of PCR-restriction enzyme analysis of the hsp65 gene (PRA-hsp65). In order
      to investigate the diversity of M. abscessus type 2 clinical isolates and to
      assess whether this epidemic strain was present in specimens from nonsurgical
      patients, we studied 52 isolates from 38 patients showing this characteristic PRA
      hsp65 pattern obtained between 2005 and 2009. All isolates were identified by
      sequencing of region V of the rpoB gene and typed by pulsed-field gel
      electrophoresis (PFGE) using two restriction enzymes, DraI and AseI. Seven
      isolates obtained from sputum, bronchoalveolar lavage fluid, and urine in three
      different Brazilian states showed rpoB sequences 100% similar to the rpoB
      sequence of epidemic strain INCQS 594 and PFGE patterns highly related to the
      patterns of isolates, evidencing the presence of the epidemic strain in isolates
      from patients not associated with the surgical epidemic. The remaining isolates
      showed diverse rpoB sequences, with the highest similarities being to the
      corresponding sequences of M. massiliense(T) CIP 108297 (21 isolates), M.
      bolletii(T) CIP 108541 (19 isolates), or M. abscessus(T) ATCC 19977 (5 isolates).
      Two additional clusters could be detected by PFGE. PFGE showed 100% typeability
      and reproducibility and discriminatory powers, calculated by Simpson's index of
      diversity, of 0.978 (DraI) and 0.986 (AseI), confirming its suitability for the
      discrimination of M. abscessus type 2 isolates.

PMID- 21084522
TI  - Development and characterization of a highly specific and sensitive SYBR green
      reverse transcriptase PCR assay for detection of the 2009 pandemic H1N1 influenza
      virus on the basis of sequence signatures.
AB  - The emergence and rapid spread of the 2009 H1N1 pandemic influenza virus showed
      that many diagnostic tests were unsuitable for detecting the novel virus
      isolates. In most countries the probe-based TaqMan assay developed by the U.S.
      Centers for Disease Control and Prevention was used for diagnostic purposes. The
      substantial sequence data that became available during the course of the pandemic
      created the opportunity to utilize bioinformatics tools to evaluate the unique
      sequence properties of this virus for the development of diagnostic tests. We
      used a comprehensive computational approach to examine conserved 2009 H1N1
      sequence signatures that are at least 20 nucleotides long and contain at least
      two mismatches compared to any other known H1N1 genome. We found that the
      hemagglutinin (HA) and neuraminidase (NA) genes contained sequence signatures
      that are highly conserved among 2009 H1N1 isolates. Based on the NA gene
      signatures, we used Visual-OMP to design primers with optimal hybridization
      affinity and we used ThermoBLAST to minimize amplification artifacts. This
      procedure resulted in a highly sensitive and discriminatory 2009 H1N1 detection
      assay. Importantly, we found that the primer set can be used reliably in both a
      conventional TaqMan and a SYBR green reverse transcriptase (RT)-PCR assay with no
      loss of specificity or sensitivity. We validated the diagnostic accuracy of the
      NA SYBR green assay with 125 clinical specimens obtained between May and August
      2009 in Chile, and we showed diagnostic efficacy comparable to the CDC assay. Our
      approach highlights the use of systematic computational approaches to develop
      robust diagnostic tests during a viral pandemic.

PMID- 21084523
TI  - Identification of oseltamivir resistance among pandemic and seasonal influenza A
      (H1N1) viruses by an His275Tyr genotyping assay using the cycling probe method.
AB  - Neuraminidase inhibitors are agents used against influenza viruses; however, the
      emergence of drug-resistant strains is a major concern. Recently, the prevalence
      of oseltamivir-resistant seasonal influenza A (H1N1) virus increased globally and
      the emergence of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses
      was reported. In this study, we developed a cycling probe real-time PCR method
      for the detection of oseltamivir-resistant seasonal influenza A (H1N1) and
      pandemic influenza A (H1N1) 2009 viruses. We designed two sets of primers and
      probes that were labeled with 6-carboxyfluorescein or 6-carboxy-X-rhodamine to
      identify single nucleotide polymorphisms (SNPs) that correspond to a histidine
      and a tyrosine at position 275 in the neuraminidase protein, respectively. These
      SNPs confer susceptibility and resistance to oseltamivir, respectively. In the
      2007-2008 season, the prevalence of oseltamivir-resistant H1N1 viruses was 0%
      (0/72), but in the 2008-2009 season, it increased to 100% (282/282). In the 2009
      2010 season, all of the pandemic influenza A (H1N1) 2009 viruses were susceptible
      to oseltamivir (0/73, 0%). This method is sensitive and specific for the
      screening of oseltamivir-resistant influenza A (H1N1) viruses. This method is
      applicable to routine laboratory-based monitoring of drug resistance and patient
      management during antiviral therapy.

PMID- 21084524
TI  - Multiple-locus variable-number tandem repeat analysis of Neisseria gonorrhoeae.
AB  - The prevalence of Neisseria gonorrhoeae in the Netherlands has increased in
      recent years. A multiple-locus variable-number tandem repeat analysis (MLVA) was
      developed to assess the molecular epidemiology of N. gonorrhoeae and to elucidate
      transmission networks in high-risk groups in Amsterdam. The MLVA was evaluated
      using 5 variable-number tandem repeat (VNTR) loci with various degrees of
      polymorphism that were amplified in 2 multiplex PCRs and were then separated and
      sized on an automated sequencer. The assessed number of repeats was used to
      create MLVA profiles that consisted of strings of 5 integers. The stability of
      the VNTR loci was assessed using isolates obtained from multiple anatomical
      locations from the same patient (n = 118) and from patients and their sexual
      partners (n = 55). When isolates with a single locus variant were considered to
      belong to the same MLVA type, 87% of samples from multiple anatomical locations
      and 88% of samples from sexual partners shared an MLVA type. MLVA was ultimately
      performed on 880 isolates that were previously genotyped by restriction fragment
      length polymorphism (RFLP) analysis of the por-opa genes. Hierarchical cluster
      analysis of the MLVA profiles from 716 patient visits (one anatomical location
      per visit) classified 430 patient visits into 14 larger clusters (>=10 patient
      visits). In 7 clusters, 81% to 100% of isolates came from men who have sex with
      men (MSM); in 5 clusters, 79% to 100% of isolates came from heterosexuals; and 2
      clusters contained isolates from fully mixed populations. Clusters also differed
      in characteristics such as ethnic background and coinfections. MLVA provided
      accurate identification of genetically related N. gonorrhoeae strains and
      revealed clusters of MSM and heterosexuals reflecting distinct transmission
      networks.

PMID- 21084525
TI  - I am against us? Unpacking cultural differences in ingroup favoritism via
      dialecticism.
AB  - The authors proposed a novel explanation for cultural differences in ingroup
      favoritism (dialecticism) and tested this hypothesis across cultures/ethnicities,
      domains, and levels of analysis (explicit vs. implicit, cognitive vs. affective).
      Dialecticism refers to the cognitive tendency to tolerate contradiction and is
      more frequently found among East Asian than North American cultures. In Study 1,
      Chinese were significantly less positive, compared to European Americans, in
      their explicit judgments of family members. Study 2 investigated ingroup
      attitudes among Chinese, Latinos, and European Americans. Only Chinese
      participants showed significant in-group derogation, relative to the other
      groups, and dialecticism (Dialectical Self Scale) was associated with
      participants' in group attitudes. Study 3 manipulated dialectical versus linear
      lay beliefs; participants primed with dialecticism showed more negative, explicit
      ingroup attitudes. Although ingroup disfavoring tendencies were more prevalent
      among Chinese across studies, they may be a reflection of one's culturally based
      lay beliefs rather than deep-rooted negative feelings toward one's ingroup.

PMID- 21084526
TI  - What your best friend sees that I don't see: comparing female close friends and
      casual acquaintances on the perception of emotional facial expressions of varying
      intensities.
AB  - It is often assumed that intimacy and familiarity will lead to better and more
      effective emotional communication between two individuals. However, research has
      failed to unequivocally support this claim. The present study proposes that close
      dyads exhibit superiority in the decoding of subdued facial cues than in the
      decoding of highly intense expressions. A total of 43 close friend dyads and 49
      casual acquaintance dyads (all women) were compared on their recognition of their
      partner's and a stranger's subdued facial expressions. Dyadic analyses indicate
      that close friends were more accurate and also improved more rapidly than casual
      acquaintances in decoding one other's subdued expressions of sadness, anger, and
      happiness, especially the two negative emotions, but not in detecting the
      stranger's subdued expressions. The results strongly suggest that intimacy
      fosters more accurate decoding of subdued facial expressions.

PMID- 21084527
TI  - Neuroprotective effects of resveratrol derivatives from the roots of Vitis
      thunbergii var. sinuate against glutamate-induced neurotoxicity in primary
      cultured rat cortical cells.
AB  - We observed that an aqueous extract of this medicinal plant exhibited significant
      neuroprotection against glutamate-induced toxicity in primary cultured rat
      cortical cells from methanol extracts of the roots of Vitis thunbergii var.
      sinuate (Vitaceae). To further clarify the underlying neuroprotective mechanisms
      of this observed effect, we isolated and identified various active fractions and
      components. By using such fractionation procedures, five resveratrol derivatives 
      vitisinols A (1), B (2), C (3), (+)-vitisin A (4), and (+)-vitisin C (5) - were
      isolated from the methanol extracts from the roots of V. thunbergii var. sinuate.
      Among these five resveratrol derivatives, 3 exhibited most significant
      neuroprotective activity against glutamate-induced neurotoxicity, as indicated by
      a cell viability of approximately 75%-85%, at concentrations ranging from 0.1 MUM
      to 10 MUM. These findings indicate that the neuroprotective effects of V.
      thunbergii var. sinuate might be due to the inhibition of glutamate-induced
      toxicity by resveratrol derivatives present in the plant.

PMID- 21084528
TI  - Post-mortem toxicological urine screening in cause of death determination.
AB  - This study evaluated standard toxicology screening by forensic physicians during
      external post-mortem examination. Collected urine samples of decedents were
      screened on-site for the presence of 10 commonly used drugs by means of a rapid
      multidrug test. Urine samples of 53% of the cases appeared to be positive for one
      or more compounds. Importantly, several cases were revealed which were positive
      for toxicology screening without indications for use of these drugs at the scene
      of death or from medical history. Based on these (preliminary) results, further
      action to incorporate routine post-mortem toxicology as a tool in forensic death
      investigation is recommended.

PMID- 21084530
TI  - Limb-length discrepancy as a cause of plantar fasciitis.
AB  - BACKGROUND: Anisomelia, or limb-length discrepancy, has disruptive effects on
      gait, posture, and ambulation. Limb-length discrepancy has been shown to be a
      factor in stress fractures in the femur and tibia, and the longer limb, a
      contributing factor in the development of low-back pain, a cause of scoliosis. We
      sought to determine whether limb-length discrepancy contributes to the frequency
      and severity of plantar fasciitis. METHODS: We enrolled 26 patients who met the
      inclusion criteria. Direct and indirect methods were used to measure limb-length
      discrepancy. We took measurements from the anterior superior iliac spine to the
      medial malleolus and from the umbilicus to the medial malleolus and performed the
      block test. Body mass index (the weight in kilograms divided by the square of the
      height in meters) was also recorded for all of the patients. RESULTS: There is
      enough evidence to support the fact that the pain location and the longer limb
      are associated (Fisher test P < .0001). There was not enough evidence in this
      study to illustrate that body mass index was related to pain location (Fisher
      test P = .7411). CONCLUSIONS: There has been little research on etiology and
      treatment correlation. These results indicate a strong correlation between a
      longer limb and unilateral plantar fasciitis pain.

PMID- 21084529
TI  - Age differences in hopelessness and toe pain in persons with insulin-dependent
      and non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Several studies have established an association between diabetic
      neuropathy and depressive symptoms. There is a link between depression and
      peripheral neuropathy in diabetic patients, suggesting an increased likelihood
      that diabetic patients will experience depressive symptoms related to lower
      extremity peripheral neuropathy and arthritis during middle age and later life.
      The goal of this investigation was to determine whether there are age differences
      between insulin-dependent and non-insulin-dependent diabetic patients regarding
      their feelings of hopelessness and toe pain. METHODS: A large population-based
      sample of 32,006 adults from the 1998 National Health Interview Survey was
      analyzed with multivariate statistical procedures. We performed chi2 and
      correlation procedures to test the null hypothesis that there are no age or sex
      differences between insulin-dependent and non-insulin-dependent diabetic patients
      in their reporting of feelings of hopelessness and toe pain symptoms in the
      previous 12 months. RESULTS: There were significant differences between age and
      sex groups of insulin-dependent and non-insulin-dependent diabetic patients in
      reporting feelings of hopelessness and toe pain symptoms, rejecting the null
      hypothesis. Correlational analysis conducted between the variables of
      hopelessness and toe pain yielded significant correlations in insulin-dependent
      (r = .28; P = .0009; alpha = .05), and non-insulin-dependent (r = 0.19; P = .001;
      alpha = .05) women older than 61 years, concluding that diabetic women are more
      likely to experience hopelessness and toe pain in that age group regardless of
      insulin status. CONCLUSIONS: Clinicians should incorporate depression and toe
      pain symptoms into their assessment and treatment, especially in diabetic women
      older than 61 years.

PMID- 21084531
TI  - Shoe preference based on subjective comfort for walking and running.
AB  - BACKGROUND: Subjective comfort of footwear is important for shoe and orthosis
      design. This study compared shoe preferences between walking and running, using
      subjective comfort as an outcome tool. METHODS: Forty-one participants walked and
      ran 20 times each along a runway in three types of footwear (cushioning,
      lightweight, and stability) and chose the model that they preferred most for
      walking and running separately based on subjective comfort. RESULTS: More
      participants preferred the cushioning model (walking, 34%; running, 41%) or the
      lightweight model (walking, 44%; running, 41%) over the stability model (walking,
      22%; running, 17%). chi2 tests revealed no differences between walking and
      running, runners and nonrunners, and lighter and heavier individuals. Women were
      more likely (odds ratio = 4.09) to prefer the lightweight model, whereas men
      preferred the cushioning (odds ratio = 2.05) and stability (odds ratio = 3.19)
      models. Most participants (71%) chose the same model for both activities.
      CONCLUSIONS: Shoe preference varies among individuals and is influenced by sex.
      Most people feel comfortable walking and running in the same shoe model.

PMID- 21084532
TI  - Clinicoradiographic assessment of flexible flatfoot in children.
AB  - BACKGROUND: Radiographic assessment is still used to evaluate flexible flatfoot
      in children. METHODS: To find a set of radiologic parameters for assessing this
      disease, we studied 53 children aged 10 to 14 years. The degree of plantar
      collapse was measured by Viladot's classification (grades 0-4). The degree of
      valgus deformity measured in the heel in a standing position, the presence of
      painful points, and functional limitation during daily-living activities were
      also reported. The children underwent standard radiography of the foot under
      load. On the dorsoplantar view, the talocalcaneal, hallux metatarsophalangeal,
      and first intermetatarsal angles were measured. On the lateral view, the
      talocalcaneal, Costa Bertani, talometatarsal, talonavicular, and tibiotalar
      angles were measured. The radiographic measurements were compared with the data
      reported in the literature and were correlated with the clinical parameters
      studied (degree of flatfoot, valgus deviation of the heel, pain, and functional
      limitation). RESULTS: The radiographic measures that resulted increased with
      respect to the reference values reported in the literature for the Costa Bertani
      (93.1% of feet), talometatarsal (93.5%), talonavicular (89.1%), and tibiotalar
      (69.7%) angles, all in the lateral view. Of the angles assessed in the
      dorsoplantar view, the hallux metatarsophalangeal (11.1%) and first
      intermetatarsal (24.2%) angles were increased. The degree of flatfoot was
      correlated with the Costa Bertani angle (P < .0005). In the group with pain, the
      lateral talocalcaneal (P = .016) and first intermetatarsal (P = .02) angles were
      increased compared within the group without pain. CONCLUSIONS: Despite technical
      limitations, we still consider standard radiography of the foot, combined with
      clinical examination, to be a valid tool for assessing flexible flatfoot in
      children, especially when surgical treatment is expected and when a basic measure
      of the structural setup of the foot is necessary.

PMID- 21084533
TI  - Orthotic devices with out-toeing wedge as treatment for in-toed gait in children.
AB  - BACKGROUND: Orthotic devices are used to help children progressively acquire a
      more physiologic walking pattern. METHODS: To determine the effect of an orthotic
      device with an out-toeing wedge along with a physiologic shoe as treatment for in
      toed gait, angle of gait was measured in 48 children aged 3 to 14 years with in
      toed gait. The following comparisons were made: angle of gait in children unshod
      versus children shod without treatment, angle of gait in children shod without
      treatment versus children shod plus orthoses, and angle of gait in children
      unshod versus children shod plus orthoses. RESULTS: Using a correctly fitting
      shoe increased the angle of gait in a nonsignificant manner, but a significant
      increase was revealed in the comparison of the angle of gait in children unshod
      versus children under treatment. The results showed that the behavior in boys and
      girls was similar to that in the total sample. Regarding side, the corrective
      effect of the orthotic device was similar in the two feet. However, the data
      showed a greater corrective effect of the shoe in the right foot. CONCLUSIONS:
      Orthotic devices with out-toeing wedge combined with correctly fitting shoes, as
      well as shoes alone, are useful tools in the treatment of in-toed gait in
      children.

PMID- 21084534
TI  - The role of institutional selectivity in the prediction of podiatric medical
      school performance.
AB  - BACKGROUND: This pilot study explores the influence of preadmission data on
      podiatric medical school performance, specifically, the role of undergraduate
      institutional selectivity. This type of study has never been described in the
      podiatric medical education literature. We conducted a longitudinal analysis of
      preadmission data on 459 students from the graduating classes of 2000 to 2009 at
      the College of Podiatric Medicine and Surgery at Des Moines University. METHODS:
      Multivariate linear regression was used to assess the relationship between
      performance during the first year of podiatric medical school and a set of
      independent variables that represent certain preadmission student
      characteristics. Student demographic characteristics, such as race/ethnicity and
      sex, were also included in the regression analysis as control variables. RESULTS:
      The regression analysis revealed that ethnic origin, undergraduate grade point
      average, Medical College Admission Test biological science and verbal reasoning
      scores, and institutional selectivity together had a significant effect on the
      dependent variable (F = 18.3; P < .001). The variance for the independent
      variable/constant variables was 32%. Almost twice as many students were dismissed
      or withdrew in poor academic standing who attended undergraduate institutions in
      the lowest selectivity category. CONCLUSIONS: This analysis revealed that in the
      College of Podiatric Medicine and Surgery, some preadmission variables, such as
      institutional selectivity, undergraduate grade point average, ethnic origin, and
      Medical College Admission Test verbal reasoning and biological science scores,
      are statistically significant in predicting first-year podiatric medical school
      grade point average. The selectivity of a student's undergraduate institution
      should be considered when screening potential podiatric medical school
      applicants.

PMID- 21084535
TI  - Intraosseous lipoma: a report of two cases with use of tricalcium phosphate bone
      void filler.
AB  - Intraosseous lipoma is a rare bone tumor that may be encountered in clinical
      practice. It is benign and is described as a well-defined, radiolucent lesion
      that must be differentiated from other lytic lesions. Most of these lesions may
      be treated without surgery; however, when surgery is needed, the classic approach
      involves curettage and packing using autologous bone grafts, allografts, or
      synthetic bone substitutes. This article reports two cases using a synthetic bone
      substitute, TheriLok, to fill the void made from surgical curettage of the
      intraosseous lipoma. Both patients tolerated the TheriLok bone substitute without
      developing adverse reactions and precluded the need for a secondary donor site.

PMID- 21084536
TI  - Deep soft-tissue necrosis of the foot and ankle caused by catfish envenomation: a
      case report.
AB  - Catfish envenomations represent a relatively rare cause of complications in
      podiatric medicine. We report a case of an unusual event eliciting a severe soft
      tissue necrosis in a 21-year-old man and his complicated wound-healing process.
      This case reviews the potential complications of catfish envenomations.

PMID- 21084537
TI  - A report of a rare case of myxoinflammatory fibroblastic sarcoma.
AB  - Myxoinflammatory fibroblastic sarcoma of the soft tissues is a rare low-grade
      tumor of uncertain origin that most often occurs on the extremities of adults.
      The tumor predominantly involves the subcutaneous tissues of the hands and feet.
      Despite being a rare neoplasm, owing to its varied histologic appearance,
      myxoinflammatory fibroblastic sarcoma should be differentiated from various
      benign and malignant soft-tissue lesions. Myxoinflammatory fibroblastic sarcoma
      has been well described in pathology journals but not in the surgical literature.
      We report a case of myxoinflammatory fibroblastic sarcoma in a 19-year-old man
      with a plantar ulcer lesion in his left foot. To our knowledge, this is the first
      reported case in the literature involving the epidermis.

PMID- 21084538
TI  - Angiokeratoma presenting as plantar verruca: a case study.
AB  - One of the more frequent pathologic conditions that podiatric physicians are
      confronted with is plantar verrucae. Plantar verrucae have been studied
      extensively in terms of morphological features and incidence in the population at
      large and in patients with human immunodeficiency virus infection. Solitary
      angiokeratomas can be morphologically similar to plantar verrucae, presenting as
      hyperkeratotic pedunculated lesions. We present a unique case study of a 40-year
      old man with human immunodeficiency virus with a painful solitary angiokeratoma
      masquerading as plantar verrucae. The lesion demonstrated clinical signs
      consistent with those highlighted in the literature for verrucae, namely, showing
      as red and black lacunae, punctuated hyperkeratotic epidermis. We propose that
      solitary angiokeratomas should be an important part of a podiatric physician's
      differential diagnosis in the lower extremity owing to the similarity of
      morphological features with plantar verrucae.

PMID- 21084539
TI  - Diffuse large B-cell lymphoma of the ankle: a case study of surgical intervention
      and outcome.
AB  - The most common type of non-Hodgkin's lymphoma is the B-cell type. We report
      herein a type of B-cell lymphoma in an adult ankle. A 63-year-old woman presented
      with a painful growth on the anteromedial aspect of her right ankle that was
      later diagnosed as a form of non-Hodgkin's lymphoma. Clinically, the single mass
      appeared bluish in color, painful on palpation, and warm to the touch. The
      overlying skin was friable, and the lesion did not transilluminate.
      Histopathologic examination revealed a diffuse large B-cell lymphoma of germinal
      center origin on surgical excision. This case report focuses on the clinical
      presentation, surgical intervention, and overall outcome of a rare case of
      lymphoma of the ankle.

PMID- 21084540
TI  - Legal aspects of podiatric pain management.
AB  - The topic of pain management remains a minor component of the formal education
      and training of residents and physicians in the United States. Misguided
      attitudes concerning acute and chronic pain management, in addition to
      reservations about the legal aspects of pain management, often translate into a
      "fear of the unknown" when it comes to narcotic prescription. The intentionally
      limited scope of this review is to promote an understanding of the laws
      regulating pain management practices in the United States and to provide
      recommendations for appropriate pain management assessment and documentation
      based on the Model Policy for the Use of Controlled Substances for the Treatment
      of Pain established by the Federation of State Medical Boards of the United
      States.

PMID- 21084541
TI  - In-shoe pressure measurement and foot orthosis research: a giant leap forward or
      a step too far?
AB  - Foot orthoses are believed to exert their therapeutic effect on the human
      locomotor apparatus by altering the location, magnitude, and temporal patterns of
      ground reaction forces acting on the plantar foot during weightbearing
      activities. In-shoe pressure-measurement systems are increasingly being used by
      clinicians and researchers to assess kinetic changes at the foot-orthosis
      interface to better understand the function of foot orthoses and to derive more
      efficacious treatments for many painful foot and lower-extremity abnormalities.
      This article explores how the inherent three-dimensional surface topography and
      load-deformation characteristics of foot orthoses may challenge the validity,
      reliability, and clinical usefulness of the data obtained from in-shoe pressure
      measurement systems in the context of foot orthotic therapy and research. The
      inability of in-shoe pressure-measurement systems to measure shearing forces
      beneath the foot, the required bending of the flat two-dimensional sensor insole
      to fit the pressure insole to the three-dimensional curves of the orthosis, the
      subsequent unbending of the sensor insole to display it on a computer monitor,
      and variations in the load-deformation characteristics of orthoses are all
      sources of potential error in examination of the kinetic effects of foot
      orthoses. Consequently, caution is required when interpreting the results of
      orthotic research that has used in-shoe pressure insole technology. The
      limitations of the technology should also be given due respect when in-shoe
      pressure measurement is used to make clinical decisions and prescribe custom foot
      orthoses for patients.

PMID- 21084544
TI  - Running up that hill: how pulmonary rehabilitation can be enhanced by
      understanding patient perceptions of their condition.

PMID- 21084545
TI  - COPD, chronic bronchitis and capacity for day-to-day activities: negative impact
      of illness on the health-related quality of life.
AB  - The aim of this study was to investigate the negative impact of illness on health
      related quality of life (HRQoL) of people with chronic obstructive pulmonary
      disease (COPD) or chronic bronchitis. The study population consisted of the
      participants (N = 8028) of a health examination survey conducted in Finland. The
      sample in the present substudy was composed of 4718 participants who had complete
      information about spirometry. Variables age, gender, body mass index (BMI),
      illnesses, smoking in lifetime, education, FEV1% and incomes were entered in
      blockwise bivariate regression analysis to examine the relationships between
      capability for day-to-day activities (physical, psychological and social
      functioning) of those with COPD. Also, COPD (n = 277) and chronic bronchitis (n =
      630) were compared with the general population (n = 3817). Study results showed
      that women with COPD had worse HRQoL than men, regarding the activities in daily
      living (ADL; odds ratio [OR] 2.63, 95% confidence interval [Cl] 1.15-5.99),
      instrumental activities of daily living (IADL; OR 4.23, 95% Cl 1.92-9.29) and
      exercise (OR 2.66, 95% Cl 1.21-5.84). Compared with the general population,
      people with chronic bronchitis were associated with poor ADL, IADL and exercise,
      (OR 1.58, 95% Cl 1.32- 1.92). Those with COPD, had difficulties managing in ADL
      (OR 4.02, 95% Cl 2.98-5.44), IADL (OR 3.27, 95% Cl 2.43-4.39), exercise (OR 3.35,
      95% Cl 2.47 to 4.53). In this representative population-based sample, COPD and
      chronic bronchitis mean a significantly poor capability in physical functioning.
      People with chronic bronchitis experienced their daily life to be worse compared
      with the general population. Reductions in physical functioning for women and
      especially with COPD were also noteworthy.

PMID- 21084546
TI  - Evaluation of a novel sputum clearance technique--hydro-acoustic therapy (HAT) in
      adult patients with cystic fibrosis: a feasibility study.
AB  - This study was designed to investigate the efficacy, safety and patients'
      acceptance of a novel system for sputum clearance--Hydro Acoustic Therapy (HAT)
      in patients with cystic fibrosis (CF). This is a prospective crossover study
      where 18 patients received 6 sessions of physiotherapy over 6 separate days.
      These consisted of 2 sessions of either HAT, flutter valve or and sitting in the
      bath with sounds without vibration (placebo) for 30 minutes each. The efficacy
      was investigated by measuring the weight of wet and dry sputum after each session
      and by change in spirometry values. The preference was assessed by a
      questionnaire completed by patients at the end of the study about their
      preference of which type of physiotherapy received. The weight of both dry and
      wet sputum produced was similar in the 3 arms of the study. Spirometry values but
      not oxygen saturation were reduced after HAT and flutter therapy sessions. HAT
      therapy was preferred to flutter and placebo in terms of breathlessness, ease of
      sputum production and relaxation. Of the patients, 70% stated that they would
      choose HAT as their preferred physiotherapy method compared to 0% for flutter
      (chi(2) = 20.3, p < 0.0001). There were no procedure-related complications in any
      of the 3 arms of the study. HAT was found to be safe, well tolerated and favoured
      by the majority of CF patients. The effect of HAT, however, on sputum production
      was not superior to flutter or placebo.

PMID- 21084547
TI  - Pulmonary rehabilitation reduces depression and enhances health-related quality
      of life in COPD patients--especially in patients with mild or moderate disease.
AB  - The first objective of the study was to evaluate a 4-week inpatient pulmonary
      rehabilitation program on exercise capacity, health-related quality of life
      (HRQL) and psychological distress in patients with COPD. The second objective was
      to investigate the influence of gender, age, disease severity, co-morbidity,
      anxiety and depression on improved HRQL after rehabilitation. The study comprised
      136 consecutive patients from baseline to follow-up with mild-to-severe COPD.
      Exercise capacity was measured by the 6-min walking distance test, disease
      severity by spirometric tests, HRQL by The St. George's Respiratory Questionnaire
      and psychological distress by the The Hospital Anxiety and Depression Scale.
      Variables on socio-demography and co-morbidity were self-reported. Exercise
      capacity was improved from baseline to follow-up with a score difference of +44
      metres (p = 000). Except for the activity score, HRQL was significantly improved:
      a change of -3.5 for the symptom score (p = 014), -3.1 for the total score (p =
      003) and a clinical significant change of - 4.0 for the impact score (p = 002).
      The anxiety score did not change significantly after rehabilitation (-0.1, p =
      545), though there was a significant reduction of the depression score (-0.8, p =
      002) and a 10.4% reduction in the prevalence of possible depression cases (p =
      017). Patients with forced expiratory volume in 1 second >=50% predicted were 4.2
      times more likely to achieve a clinical significant improved HRQL after
      rehabilitation than patients with forced expiratory volume in 1 second <50%
      predicted (95% confidence interval [CI] 1.7-10.3, p = 002). A 4-week inpatient
      rehabilitation program improves HRQL and exercise capacity and reduces depression
      in COPD patients. Patients with mild or moderate disease are more likely to
      achieve an improved HRQL after rehabilitation than patients with severe or very
      severe disease.

PMID- 21084548
TI  - The endurance shuttle walk test: an alternative to the six-minute walk test for
      the assessment of ambulatory oxygen.
AB  - UK guidelines for domiciliary oxygen have suggested the six-minute walk test or
      shuttle walk tests as suitable functional measures for the clinical assessment of
      ambulatory oxygen (AO). To date, there is limited evidence that would support the
      use of shuttle walk tests as assessment tools for AO. The endurance shuttle walk
      test (ESWT) is used increasingly as an assessment tool within pulmonary
      rehabilitation (PR) but its potential as an investigative test for AO has not
      been explored. Using the same test for both PR and AO assessment is appealing
      since it would improve efficiency and act to standardise outcome measures in this
      patient population. The aim of this study was to examine the responsiveness and
      repeatability of the ESWT to AO and to compare the response with that of the six
      minute walk test (6MWT). Twenty-three patients with chronic obstructive pulmonary
      disease (COPD) performed, in random order, the ESWT and the 6MWT on air and
      whilst breathing AO. Oxygen saturation and Borg ratings of breathlessness and
      perceived exertion were recorded. On a third day, eleven patients repeated the
      ESWT with AO in order to measure repeatability. There was a significantly greater
      change in the ESWT with oxygen than the change recorded from the 6MWT (66 [91] vs
      6 [28] m respectively; P < .05). When repeated on a separate day, the mean
      difference (95% CI) between distances walked on the ESWT with AO was 0.91 (-47,
      49) m. The ESWT was more responsive than the 6MWT for detecting improvements in
      walking endurance whilst breathing AO.

PMID- 21084549
TI  - Review series: Aspects of interstitial lung disease. Sarcoidosis.

PMID- 21084550
TI  - Review series: What goes around, comes around: childhood influences on later lung
      health? Long-term follow-up of infants with lung disease of prematurity.
AB  - The incidence of live preterm birth is increasing and concomitantly the survival
      of preterm babies has increased over the last 30 years due to advances in
      neonatal care. Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease
      that develops as a consequence of perinatal and/or neonatal lung injury following
      preterm birth and the pathology has also changed with changes in neonatal care.
      There are data suggesting that there is increased respiratory morbidity of ex
      preterm subjects in childhood. It is only now that large populations of preterm
      subjects are reaching adulthood and may be at risk of persistent respiratory
      morbidity. This review will summarize the current knowledge in adulthood of
      respiratory sequelae following preterm birth; specifically it will review
      respiratory symptoms, pulmonary function, exercise capacity and structural lung
      disease as determined by high resolution computed tomography scans in ex-preterm
      survivors with and without BPD. Whether prematurity-related lung disease is
      associated with chronic obstructive airways disease will be discussed.

PMID- 21084552
TI  - Magnetic resonance imaging predictors of treatment response in first-episode
      schizophrenia.
AB  - Identifying neurobiological predictors of response to antipsychotics in patients
      with schizophrenia is a critical goal of translational psychiatry. Few studies,
      however, have investigated the relationship between indices of brain structure
      and treatment response in the context of a controlled clinical trial. In this
      study, we sought to identify magnetic resonance (MR) imaging measures of the
      brain that predict treatment response in patients experiencing a first-episode of
      schizophrenia. Structural MR imaging scans were acquired in 39 patients
      experiencing a first-episode of schizophrenia with minimal or no prior exposure
      to antipsychotics participating in a double-blind 16-week clinical trial
      comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were
      classified as responders by meeting operationally defined treatment response
      criteria on 2 consecutive study visits. Fourteen patients never responded to
      antipsychotic medication at any point during the clinical trial. MR imaging scans
      were also acquired in 45 age- and sex-matched healthy volunteers. Cortical
      pattern matching methods were used to compare cortical thickness and asymmetry
      measures among groups. Statistical mapping results, confirmed by permutation
      testing, indicated that responders had greater cortical thickness in occipital
      regions and greater frontal cortical asymmetry compared with nonresponders.
      Moreover, among responders, greater thickness in temporal regions was associated
      with less time to respond. Our findings are consistent with the hypothesis that
      plasticity and cortical thickness may be more preserved in responders and that MR
      imaging may assist in the prediction of antipsychotic drug response in patients
      experiencing a first-episode of schizophrenia.

PMID- 21084551
TI  - NMDA receptor hypofunction induces dysfunctions of energy metabolism and
      semaphorin signaling in rats: a synaptic proteome study.
AB  - There is considerable evidence to suggest that aberrations of synapse
      connectivity contribute to the pathophysiology of schizophrenia and that N-methyl
      D-aspartate (NMDA) receptor-mediated glutamate transmission is especially
      important. Administration of MK-801 ([+]-5-methyl-10, 11-dihydro-5H-dibenzo-[a,
      d]-cycloheptene-5, 10-iminehydrogenmaleate) induces hypofunction of NMDA
      receptors in rats, which are widely used as a model for schizophrenia. We
      investigated synaptosomal proteome expression profiling of the cerebral cortex of
      MK-801-treated Sprague-Dawley rats using the 2-dimensional difference gel
      electrophoresis method, and 49 differentially expression proteins were
      successfully identified using Matrix-Assisted Laser Desorption/Ionization Time-of
      Flight/Time-of-Flight mass spectrometry. We carried out a literature search for
      further confirmation of subsynaptic locations and to explore the relevance to the
      diseases of differentially expressed proteins. Ingenuity Pathways Analysis (IPA)
      was used to further examine the underlying relationship between the changed
      proteins. The network encompassing "cell morphology, cell-to-cell signaling and
      interaction, nervous system development and function" was found to be
      significantly altered in the MK-801-treated rats. "Energy metabolism" and
      "semaphorin signaling in neurons" are the most significant IPA canonical pathways
      to be affected by MK-801 treatment. Using western blots, we confirmed the
      differential expression of Camk2a, Crmp2, Crmp5, Dnm1, and Ndufs3 in both
      synaptosome proteins and total proteins in the cerebral cortex of the rats. Our
      study identified the change and/or response of the central nervous transmission
      system under the stress of NMDA hypofunction, underlining the importance of the
      synaptic function in schizophrenia.

PMID- 21084553
TI  - The contribution of risk factors to the higher incidence of invasive and in situ
      breast cancers in women with higher levels of education in the European
      prospective investigation into cancer and nutrition.
AB  - The authors investigated the role of known risk factors in educational
      differences in breast cancer incidence. Analyses were based on the European
      Prospective Investigation Into Cancer and Nutrition and included 242,095 women,
      433 cases of in situ breast cancer, and 4,469 cases of invasive breast cancer.
      Reproductive history (age at first full-term pregnancy and parity), exposure to
      endogenous and exogenous hormones, height, and health behaviors were accounted
      for in the analyses. Relative indices of inequality (RII) for education were
      estimated using Cox regression models. A higher risk of invasive breast cancer
      was found among women with higher levels of education (RII = 1.22, 95% confidence
      interval (CI): 1.09, 1.37). This association was not observed among nulliparous
      women (RII = 1.13, 95% CI: 0.84, 1.52). Inequalities in breast cancer incidence
      decreased substantially after adjusting for reproductive history (RII = 1.11, 95%
      CI: 0.98, 1.25), with most of the association being explained by age at first
      full-term pregnancy. Each other risk factor explained a small additional part of
      the inequalities in breast cancer incidence. Height accounted for most of the
      remaining differences in incidence. After adjusting for all known risk factors,
      the authors found no association between education level and risk of invasive
      breast cancer. Inequalities in incidence were more pronounced for in situ breast
      cancer, and those inequalities remained after adjustment for all known risk
      factors (RII = 1.61, 95% CI: 1.07, 2.41), especially among nulliparous women.

PMID- 21084554
TI  - Accuracy of commercially available residential histories for epidemiologic
      studies.
AB  - A key problem facing epidemiologists who wish to account for residential mobility
      in their analyses is the cost and difficulty of obtaining residential histories.
      Commercial residential history data of acceptable accuracy, cost, and coverage
      would be of great value. The present research evaluated the accuracy of
      residential histories from LexisNexis, Inc. The authors chose LexisNexis because
      the Michigan Cancer Registry has considered using their data, they have excellent
      procedures for privacy protection, and they make available residential histories
      at 25 cents per person. Only first and last name and address at last-known
      residence are required to access the residential history. The authors compared
      lifetime residential histories collected through the use of written surveys in a
      case-control study of bladder cancer in Michigan to the 3 residential addresses
      routinely available in the address history from LexisNexis. The LexisNexis
      address matches, as a whole, accounted for 71.5% of participants' lifetime
      addresses. These results provided a level of accuracy that indicates routine use
      of residential histories from commercial vendors is feasible. More detailed
      residential histories are available at a higher cost but were not analyzed in
      this study. Although higher accuracy is desirable, LexisNexis data are a vast
      improvement over the assumption of immobile individuals currently used in many
      spatial and spatiotemporal studies.

PMID- 21084555
TI  - Genetic association and gene-environment interaction: a new method for overcoming
      the lack of exposure information in controls.
AB  - The use of a reference control panel in genome-wide association studies is an
      interesting solution to the problem of how to reduce costs. In such designs, data
      on relevant environmental factors are usually collected only in cases, making it
      more difficult to deal with potential gene-environment interactions when testing
      for genetic association. However, under certain circumstances, neglecting an
      existing interaction with the environment may be detrimental in terms of
      statistical power to detect the genetic factor. In this paper, the authors
      propose a novel method based on a multinomial logistic regression model to
      overcome the lack of environmental exposure information in controls, by
      contrasting both exposed and unexposed cases with the control sample. For each
      case group, a genetic effect-size parameter is estimated, and the genetic
      association and the gene-environment interaction are tested jointly. The authors
      evaluate the performance of this method through asymptotic computations and
      simulations of cases and population controls under different models. In the
      presence of a gene-environment interaction, this approach outperforms other
      available methods that test for genetic association and gene-environment
      interaction either separately or jointly. Interestingly, it even has better power
      than the joint test requiring full knowledge of the environmental information in
      both cases and controls.

PMID- 21084556
TI  - Mortality in the agricultural health study, 1993-2007.
AB  - Comparing agricultural cohorts with the general population is challenging because
      the general healthiness of farmers may mask potential adverse health effects of
      farming. Using data from the Agricultural Health Study, a cohort of 89,656
      pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa,
      the authors computed standardized mortality ratios (SMRs) comparing deaths from
      time of the enrollment (1993-1997) through 2007 to state-specific rates. To
      compensate for the cohort's overall healthiness, relative SMRs were estimated by
      calculating the SMR for each cause relative to the SMR for all other causes. In
      1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause
      mortality rate was less than expected (SMR(applicators) = 0.54, 95% confidence
      interval (CI): 0.52, 0.55; SMR(spouses) = 0.52, 95% CI: 0.50, 0.55). SMRs for all
      cancers, heart disease, and diabetes were significantly below 1.0. In contrast,
      applicators experienced elevated numbers of machine-related deaths (SMR = 4.15,
      95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI:
      1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the
      relative SMR analysis for applicators, the relative mortality ratio was elevated
      for lymphohematopoietic cancers, melanoma, and digestive system, prostate,
      kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for
      lymphohematopoietic cancers and malignancies of the digestive system, brain,
      breast, and ovary. Unintentional fatal injuries remain an important risk for
      farmers; mortality ratios from several cancers were elevated relative to other
      causes.

PMID- 21084557
TI  - Long-term statin use and the risk of gallstone disease: A population-based case
      control study.
AB  - Most gallstones originate from cholesterol-supersaturated bile. Statins inhibit
      hepatic cholesterol biosynthesis and therefore may reduce the risk of gallstone
      disease. Population-based evidence, however, is sparse. Thus, the authors
      conducted a population-based case-control study using medical databases from
      northern Denmark (1.7 million inhabitants) to identify 32,494 cases of gallstones
      occurring between 1996 and 2008 and to identify age-, sex-, and county-matched
      population controls for each case. Cases and their matched controls who were
      exposed to lipid-lowering drugs were categorized as current users if their last
      prescription was redeemed <=90 days before the case's diagnosis date; otherwise,
      they were categorized as former users. Conditional logistic regression was used
      to estimate adjusted odds ratios and 95% confidence intervals for gallstone
      disease in patients treated with lipid-lowering drugs. In current users, the
      adjusted odds ratios associating statin use with the occurrence of gallstone
      disease were 1.17 (95% confidence interval (CI): 1.06, 1.30) for those who had 1
      4 prescriptions, 0.89 (95% CI: 0.80, 0.97) for those who had 5-19 prescriptions,
      and 0.76 (95% CI: 0.69, 0.84) for those who had >=20 total prescriptions. In
      former users, the corresponding adjusted odds ratios were 1.24 (95% CI: 1.11,
      1.39), 0.97 (95% CI: 0.86, 1.10), and 0.79 (95% CI: 0.64, 0.97), respectively.
      The use of other lipid-lowering drugs showed no similar association.

PMID- 21084558
TI  - Adult body size, hormone receptor status, and premenopausal breast cancer risk in
      a multiethnic population: the San Francisco Bay Area breast cancer study.
AB  - Large body size has been associated with a reduced risk of premenopausal breast
      cancer in non-Hispanic white women. Data on other racial/ethnic populations are
      limited. The authors examined the association between premenopausal breast cancer
      risk and adult body size in 672 cases and 808 controls aged >=35 years from a
      population-based case-control study conducted in 1995-2004 in the San Francisco
      Bay Area (Hispanics: 375 cases, 483 controls; African Americans: 154 cases, 160
      controls; non-Hispanic whites: 143 cases, 165 controls). Multivariate adjusted
      odds ratios and 95% confidence intervals were calculated using unconditional
      logistic regression. Height was associated with increased breast cancer risk
      (highest vs. lowest quartile: odds ratio = 1.77, 95% confidence interval: 1.23,
      2.53; P(trend) < 0.01); the association did not vary by hormone receptor status
      or race/ethnicity. Body mass index (measured as weight (kg) divided by height (m)
      squared) was inversely associated with risk in all 3 racial/ethnic groups, but
      only for estrogen receptor- and progesterone receptor-positive tumors (body mass
      index >=30 vs. <25: odds ratio = 0.42; 95% confidence interval: 0.29, 0.61).
      Other body size measures (current weight, body build, adult weight gain, young
      adult weight and body mass index, waist circumference, and waist-to-height ratio)
      were similarly inversely associated with risk of estrogen receptor- and
      progesterone receptor-positive breast cancer but not estrogen receptor- and
      progesterone receptor-negative disease. Despite racial/ethnic differences in body
      size, inverse associations were similar across the 3 racial/ethnic groups when
      stratified by hormone receptor status.

PMID- 21084560
TI  - Palmitoylation and depalmitoylation dynamics at a glance.

PMID- 21084561
TI  - The role of ubiquitylation and degradation in RhoGTPase signalling.
AB  - Rho-like guanosine triphosphatases (RhoGTPases) control many aspects of cellular
      physiology through their effects on the actin cytoskeleton and on gene
      transcription. Signalling by RhoGTPases is tightly coordinated and requires a
      series of regulatory proteins, including guanine-nucleotide exchange factors
      (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation
      inhibitors (GDIs). GEFs and GAPs regulate GTPase cycling between the active (GTP
      bound) and inactive (GDP-bound) states, whereas GDI is a cytosolic chaperone that
      binds inactive RhoGTPases. Like many other proteins, RhoGTPases are subject to
      degradation following the covalent conjugation of ubiquitin. There have been
      increasing indications that ubiquitylation of small GTPases occurs in a regulated
      fashion, primarily upon activation, and is an important means to control
      signalling output. Recent work has identified cellular proteins that control
      RasGTPase and RhoGTPase ubiquitylation and degradation, allowing us to amend the
      canonical model for GTPase (in)activation. Moreover, accumulating evidence for
      indirect regulation of GTPase function through the ubiquitylation of GTPase
      regulators makes this post-translational modification a key feature of GTPase
      dependent signalling pathways. Here, we will discuss these recent insights into
      the regulation of RhoGTPase ubiquitylation and their relevance for cell
      signalling.

PMID- 21084559
TI  - Hippo signaling at a glance.

PMID- 21084562
TI  - Heterologous expression reveals distinct enzymatic activities of two DOT1 histone
      methyltransferases of Trypanosoma brucei.
AB  - Dot1 is a highly conserved methyltransferase that modifies histone H3 on the
      nucleosome core surface. In contrast to yeast, flies, and humans where a single
      Dot1 enzyme is responsible for all methylation of H3 lysine 79 (H3K79), African
      trypanosomes express two DOT1 proteins that methylate histone H3K76
      (corresponding to H3K79 in other organisms) in a cell-cycle-regulated manner.
      Whereas DOT1A is essential for normal cell cycle progression, DOT1B is involved
      in differentiation and control of antigenic variation of this protozoan parasite.
      Analysis of DOT1A and DOT1B in trypanosomes or in vitro, to understand how H3K76
      methylation is controlled during the cell cycle, is complicated by the lack of
      genetic tools and biochemical assays. To eliminate these problems, we developed a
      heterologous expression system in yeast. Whereas Trypanosoma brucei DOT1A
      predominantly dimethylated H3K79, DOT1B trimethylated H3K79 even in the absence
      of dimethylation by DOT1A. Furthermore, DOT1A activity was selectively reduced by
      eliminating ubiquitylation of H2B. The tail of histone H4 was not required for
      activity of DOT1A or DOT1B. These findings in yeast provide new insights into
      possible mechanisms of regulation of H3K76 methylation in Trypanosoma brucei.

PMID- 21084563
TI  - Distance between homologous chromosomes results from chromosome positioning
      constraints.
AB  - The organization of chromosomes is important for various biological processes and
      is involved in the formation of rearrangements often observed in cancer. In
      mammals, chromosomes are organized in territories that are radially positioned in
      the nucleus. However, it remains unclear whether chromosomes are organized
      relative to each other. Here, we examine the nuclear arrangement of 10
      chromosomes in human epithelial cancer cells by three-dimensional FISH analysis.
      We show that their radial position correlates with the ratio of their gene
      density to chromosome size. We also observe that inter-homologue distances are
      generally larger than inter-heterologue distances. Using numerical simulations
      taking radial position constraints into account, we demonstrate that, for some
      chromosomes, radial position is enough to justify the inter-homologue distance,
      whereas for others additional constraints are involved. Among these constraints,
      we propose that nucleolar organizer regions participate in the internal
      positioning of the acrocentric chromosome HSA21, possibly through interactions
      with nucleoli. Maintaining distance between homologous chromosomes in human cells
      could participate in regulating genome stability and gene expression, both
      mechanisms that are key players in tumorigenesis.

PMID- 21084564
TI  - REGgamma modulates p53 activity by regulating its cellular localization.
AB  - The proteasome activator REGgamma mediates a shortcut for the destruction of
      intact mammalian proteins. The biological roles of REGgamma and the underlying
      mechanisms are not fully understood. Here we provide evidence that REGgamma
      regulates cellular distribution of p53 by facilitating its multiple
      monoubiquitylation and subsequent nuclear export and degradation. We also show
      that inhibition of p53 tetramerization by REGgamma might further enhance
      cytoplasmic relocation of p53 and reduce active p53 in the nucleus. Furthermore,
      multiple monoubiquitylation of p53 enhances its physical interaction with HDM2
      and probably facilitates subsequent polyubiquitylation of p53, suggesting that
      monoubiquitylation can act as a signal for p53 degradation. Depletion of REGgamma
      sensitizes cells to stress-induced apoptosis, validating its crucial role in the
      control of apoptosis, probably through regulation of p53 function. Using a mouse
      xenograft model, we show that REGgamma knockdown results in a significant
      reduction of tumor growth, suggesting an important role for REGgamma in tumor
      development. Our study therefore demonstrates that REGgamma-mediated inactivation
      of p53 is one of the mechanisms involved in cancer progression.

PMID- 21084565
TI  - Adaptor protein XB130 is a Rac-controlled component of lamellipodia that
      regulates cell motility and invasion.
AB  - XB130 is a newly described cytosolic adaptor protein and tyrosine kinase
      substrate, involved in Src- and RET/PTC-dependent signaling. Although XB130 has
      been cloned as a homologue of actin-filament-associated protein (AFAP-110), its
      potential regulation by the actin skeleton and its putative roles in cytoskeleton
      regulation have not been addressed. Here, we show that XB130 (in contrast to AFAP
      110) exhibited robust translocation to the cell periphery in response to various
      stimuli (including epidermal growth factor, wounding and expression of
      constitutively active Rac) that elicit lamellipodium formation. In stimulated
      cells, XB130 localized to the lamellipodial F-actin meshwork. Genetic and
      pharmacological data suggest that the key trigger for XB130 recruitment is the
      formation of the branched F-actin itself. Structure-function analysis revealed
      that both the XB130 N-terminus (167 amino acids) and C-terminus (63 amino acids)
      harbor crucial regions for its translocation to lamellipodia, whereas the PH
      domains and Src-targeted tyrosines are dispensable. Importantly, in TPC1 thyroid
      papillary carcinoma cells, silencing endogenous XB130 decreased the rate of wound
      closure, inhibited matrigel invasion, reduced lamellipodial persistence and
      slowed down spreading. Thus, XB130 is a novel Rac- and cytoskeleton-regulated and
      cytoskeleton-regulating adaptor protein that exhibits high affinity to
      lamellipodial (branched) F-actin and impacts motility and invasiveness of tumor
      cells.

PMID- 21084566
TI  - Do older and younger people differ in their reported well-being? A national
      survey of adults in Britain.
AB  - AIM: To document population perceptions of well-being and predictors of self
      assessed well-being. METHODS: National face-to-face interview survey of adults
      aged >=16 years, conducted by the Office for National Statistics for their
      Omnibus Survey in Britain (response 58%; 1049 of 1823 eligible). RESULTS: People
      aged 65+ years were more likely than younger people to define well-being as being
      able to continue to do the things they had always done. Most men and women, in
      all age groups, rated their well-being and mental well-being positively. Self
      rated health, mental health symptoms, long-standing illness and social support
      were the main drivers of overall well-being in all age groups. Mental health
      symptoms, long-standing illness and social support were the main drivers of
      mental well-being. For example, in reduced multivariable models, those who
      reported no long-standing illness had almost twice the odds of others, of good,
      rather than not good, overall well-being, and over three times the odds of good,
      rather than not good, mental well-being. The odds of good versus not good overall
      well-being were also multiplied by 1.002 for each additional available person for
      comfort and support and similarly by 1.073 in relation to mental well-being.
      CONCLUSIONS: Understanding the drivers of well-being among adults, including
      older adults, is of high policy importance. Attention should be focused on
      improvements in population health and functioning and on encouraging younger and
      older people to develop and maintain social support networks and engagement in
      social activities.

PMID- 21084567
TI  - Are stroke patients' reports of home blood pressure readings reliable? Cross
      sectional study.
AB  - BACKGROUND: Home blood pressure (BP) monitoring is gaining increasing popularity
      among patients and may be useful in hypertension management. Little is known
      about the reliability of stroke patients' records of home BP monitoring.
      OBJECTIVE: To assess the reliability of home BP recording in hypertensive
      patients who had suffered a recent stroke or transient ischaemic attack. METHODS:
      Thirty-nine stroke patients (mean age 73 years) randomized to the intervention
      arm of a trial of home BP monitoring were included. Following instruction by a
      research nurse, patients recorded their BPs at home and documented them in a
      booklet over the next year. The booklet readings over a month were compared with
      the actual readings downloaded from the BP monitor and were checked for errors or
      selective bias in recording. RESULTS: A total of 1027 monitor and 716 booklet
      readings were recorded. Ninety per cent of booklet recordings were exactly the
      same as the BP monitor readings. Average booklet readings were 0.6 mmHg systolic
      [95% confidence interval (95% CI) -0.6 to 1.8] and 0.3 mmHg diastolic (95% CI 
      0.3 to 0.8) lower than those on the monitor. CONCLUSIONS: This group of elderly
      stroke patients were able to record their BPs reliably at home. Any bias was
      small and would be unlikely to affect management. Since BP readings in a GP
      surgery are often a poor indication of true BP, GPs might consider using
      hypertensive patients' records of home BP monitoring to help guide treatment
      decisions.

PMID- 21084568
TI  - How patients use access to their electronic GP record--a quantitative study.
AB  - BACKGROUND: Record access is likely to become an integral part of routine care in
      the UK. While existing research suggests that record access improves self-care
      and improves relationships between patients and clinicians, little is known about
      how patients make use of their ability to access their records or the impact that
      this has on health behaviour. AIM: To explore patients' use of access to their
      electronic GP record and the impact of that process on their health behaviour.
      METHOD: Self-administered postal questionnaire mailed from three general practice
      surgeries to patients registered to use PAERS record access system. Data were
      analysed using SPSS. Content analysis was used to analyse free-text responses.
      RESULTS: Two hundred and thirty-one of 610 patients responded. Frequent users of
      Record Access were those in poor health. Record access was used to look at test
      results and to read letters from those involved in health care. Forty-two per
      cent reported a positive impact on following medication advice and 64% a positive
      impact on following lifestyle advice. Just over half the sample felt accessing
      records prior to appointments saved time and wanted to share records with other
      health care providers. Approximately a third reported difficulties with
      understanding their records. CONCLUSIONS: Record access appears to have a number
      of positive outcomes and very few negative ones, although further work is needed
      to confirm this. It is used by patients to help practices improve efficiency and
      to improve compliance. It has the potential to promote and reinforce
      collaborative relationships between clinicians and patients.

PMID- 21084569
TI  - Relationships between homeoprotein EGAM1C and the expression of the placental
      prolactin gene family in mouse placentae and trophoblast stem cells.
AB  - The mouse Crxos gene encodes three structurally related homeoproteins, EGAM1,
      EGAM1N, and EGAM1C, as transcription and splicing variants. Recently, we
      identified the functions of EGAM1 and EGAM1N in the regulation of differentiation
      in mouse embryonic stem cells. However, the function of EGAM1C remains unknown.
      To explore the additional roles of these proteins, the ontogenic expression of
      the respective mRNAs in post implantation mouse embryos and extraembryonic
      tissues, particularly from embryonic day (E) 10.5 to E18.5, was analyzed. The
      expression of Egam1n mRNA was specifically detected in embryos throughout this
      period, whereas that of Egam1 was undetectable in any of the tissues examined.
      However, in the placenta, Egam1c mRNA and its encoded protein were detected after
      E16.5, and these expression levels increased by E18.5 immediately before partum.
      Quantitative RT-PCR and in situ hybridization analyses in placentae revealed that
      the spatial and temporal expression patterns of the Egam1c mRNA were related to
      some extent with those of Prl3a1 and Prl5a1 and partially overlapped that of
      Prl3b1, which are members of the placental prolactin (PRL) gene family. When
      EGAM1C was overexpressed moderately in mouse trophoblast stem cells as a model
      for undifferentiated and differentiating placental cell types, the expression
      levels of endogenous Prl3b1 and Prl5a1 were enhanced under both undifferentiated
      and differentiating culture conditions. These results indicated that EGAM1C may
      play a role in the expression of members of the placental PRL gene family, such
      as Prl3b1 and Prl5a1.

PMID- 21084570
TI  - Neonatal programming by immunological challenge: effects on ovarian function in
      the adult rat.
AB  - Neonatal exposure to an immunological challenge (lipopolysaccharide, LPS)
      increases the activity of hypothalamo-pituitary-adrenal axis and sensitises the
      GNRH pulse generator to the inhibitory influence of stress in adult rats. We
      investigated the effects of neonatal exposure to LPS on various reproductive
      parameters during puberty and into adulthood in female rats. LPS (50 MUg/kg,
      i.p.) or saline was administered on postnatal days 3 and 5. Vaginal opening was
      recorded, and oestrous cyclicity was monitored immediately post puberty and again
      at 8-9 weeks of age. At 10 weeks of age, the ovaries were removed and the number
      of follicles was counted, together with the thickness of the theca interna of the
      largest antral follicles. Ovarian sympathetic nerve activity was assessed
      immunohistochemically by measurement of the levels of ovarian low-affinity
      receptor of nerve growth factor (p75NGFR). In rats exposed to LPS in early life,
      there was a significant delay in puberty and disruption of oestrous cyclicity
      immediately post puberty, which persisted into adulthood. The follicle reserve
      was decreased, the thickness of the theca interna increased and the expression
      profile of ovarian p75NGFR increased in the neonatal LPS-treated animals. These
      data suggest that exposure to LPS during early neonatal life can have long-term
      dysfunctional effects on the female reproductive system, which might involve, at
      least in part, increased ovarian sympathetic nerve activity.

PMID- 21084571
TI  - Good planning and serendipity: exploiting the Cre/Lox system in the testis.
AB  - Over the past 20 years, genetic manipulation has revolutionised our understanding
      of male reproductive development and function. The advent of transgenic mouse
      lines has permitted elegant dissection of previously intractable issues. The
      development of the Cre/Lox system, which has permitted spatial and temporal
      localisation of genetic manipulation, has expanded upon this, and now makes up
      one of the primary approaches underpinning our increasing understanding of testis
      development and function. The success of conditional gene targeting is largely
      reliant upon the choice of Cre recombinase expressing mouse line, which is
      required to specifically target the correct cell type at the correct time.
      Presupposition that Cre lines will behave as expected has been one of the main
      oversights in the design of Cre/Lox experiments, as in practice, many Cre lines
      are prone to ectopic expression (both temporal and spatial), transgene silencing
      or genetic background effects. Empirical validation of the spatiotemporal profile
      of Cre expression prior to undertaking conditional gene targeting studies is
      essential and can be achieved through a combination of molecular and
      immunohistochemical approaches, along with in vivo examination of reporter gene
      expression in targeted tissues. This paper details the key considerations
      associated with exploitation of the Cre/Lox system and highlights a variety of
      validated Cre lines that have utility for conditional gene targeting within the
      testis.

PMID- 21084572
TI  - Commentary on an article by Nathan A. Mall, MD, et al.: "Symptomatic progression
      of asymptomatic rotator cuff tears: a prospective study of clinical and
      sonographic variables".

PMID- 21084573
TI  - Commentary on an article by Won Chul Choi, MD, et al.: "Comparison between
      standard and high-flexion posterior-stabilized rotating-platform mobile-bearing
      total knee arthroplasties. A randomized controlled study".

PMID- 21084575
TI  - The influence of procedure volumes and standardization of care on quality and
      efficiency in total joint replacement surgery.
AB  - BACKGROUND: The relationship between surgeon and hospital procedure volumes and
      clinical outcomes in total joint arthroplasty has long fueled a debate over
      regionalization of care. At the same time, numerous policy initiatives are
      focusing on improving quality by incentivizing surgeons to adhere to evidence
      based processes of care. The purpose of this study was to evaluate the
      independent contributions of surgeon procedure volume, hospital procedure volume,
      and standardization of care on short-term postoperative outcomes and resource
      utilization in lower-extremity total joint arthroplasty. METHODS: An analysis of
      182,146 consecutive patients who underwent primary total joint arthroplasty was
      performed with use of data entered into the Perspective database by 3421
      physicians from 312 hospitals over a two-year period. Adherence to evidence-based
      processes of care was defined by administration of appropriate perioperative
      antibiotic prophylaxis, beta-blockade, and venous thromboembolism prophylaxis.
      Patient outcomes included mortality, length of hospital stay, discharge
      disposition, surgical complications, readmissions, and reoperations within the
      first thirty days after discharge. Hierarchical models were used to estimate the
      effects of hospital and surgeon procedure volume and process standardization on
      individual and combined surgical outcomes and length of stay. RESULTS: After
      adjustment in multivariate models, higher surgeon volume was associated with
      lower risk of complications, lower rates of readmission and reoperation, shorter
      length of hospital stay, and higher likelihood of being discharged home. Higher
      hospital volume was associated with lower risk of mortality, lower risk of
      readmission, and higher likelihood of being discharged home. The impact of
      process standardization was substantial; maximizing adherence to evidence-based
      processes of care resulted in improved clinical outcomes and shorter length of
      hospital stay, independent of hospital or surgeon procedure volume. CONCLUSIONS:
      Although surgeon and hospital procedure volumes are unquestionably correlated
      with patient outcomes in total joint arthroplasty, process standardization is
      also strongly associated with improved quality and efficiency of care. The exact
      relationship between individual processes of care and patient outcomes has not
      been established; however, our findings suggest that process standardization
      could help providers optimize quality and efficiency in total joint arthroplasty,
      independent of hospital or surgeon volume.

PMID- 21084574
TI  - Symptomatic progression of asymptomatic rotator cuff tears: a prospective study
      of clinical and sonographic variables.
AB  - BACKGROUND: The purposes of this study were to identify changes in tear
      dimensions, shoulder function, and glenohumeral kinematics when an asymptomatic
      rotator cuff tear becomes painful and to identify characteristics of individuals
      who develop pain compared with those who remain asymptomatic. METHODS: A cohort
      of 195 subjects with an asymptomatic rotator cuff tear was prospectively
      monitored for pain development and examined annually for changes in various
      parameters such as tear size, fatty degeneration of the rotator cuff muscle,
      glenohumeral kinematics, and shoulder function. Forty-four subjects were found to
      have developed new pain, and the parameters before and after pain development
      were compared. The forty-four subjects were then compared with a group of fifty
      five subjects who remained asymptomatic over a two-year period. RESULTS: With
      pain development, the size of a full-thickness rotator cuff tear increased
      significantly, with 18% of the full-thickness tears showing an increase of >5 mm,
      and 40% of the partial-thickness tears had progressed to a full-thickness tear.
      In comparison with the assessments made before the onset of pain, the American
      Shoulder and Elbow Surgeons scores for shoulder function were significantly
      decreased and all measures of shoulder range of motion were decreased except for
      external rotation at 90 degrees  of abduction. There was an increase in
      compensatory scapulothoracic motion in relation to the glenohumeral motion during
      early shoulder abduction with pain development. No significant changes were found
      in external rotation strength or muscular fatty degeneration. Compared with the
      subjects who remained asymptomatic, the subjects who developed pain were found to
      have significantly larger tears at the time of initial enrollment. CONCLUSIONS:
      Pain development in shoulders with an asymptomatic rotator cuff tear is
      associated with an increase in tear size. Larger tears are more likely to develop
      pain in the short term than are smaller tears. Further research is warranted to
      investigate the role of prophylactic treatment of asymptomatic shoulders to avoid
      the development of pain and loss of shoulder function.

PMID- 21084576
TI  - Clinical and radiographic results of metal-on-metal hip resurfacing with a
      minimum ten-year follow-up.
AB  - BACKGROUND: There was a need for information about the long-term performance of
      the modern generation of hip resurfacing implants. A retrospective review of the
      first 100 hips that had implantation of one resurfacing design and had been
      followed for a minimum of ten years was performed. METHODS: Between 1996 and
      1998, 100 CONSERVE PLUS hip resurfacing devices were implanted by a single
      surgeon in eighty-nine patients. The mean age of the patients was 49.1 years, and
      fifty-nine patients were male. Primary osteoarthritis was the etiology for sixty
      four hips. All patients were assessed clinically and radiographically. RESULTS:
      The mean duration of follow-up was 11.7 years (range, 10.8 to 12.9 years). Two
      patients were lost to follow-up, and five patients died of causes unrelated to
      the surgery. Eleven hips had conversion to total hip arthroplasty because of
      loosening of the femoral component (eight), a femoral neck fracture (one),
      recurrent subluxation (one), and late infection (one). The Kaplan-Meier
      survivorship was 88.5% at ten years. None of the resurfacing arthroplasties
      failed in the twenty-eight hips that had a femoral component of >46 mm and no
      femoral head cystic or necrotic defects of >1 cm. Five hips had narrowing of the
      femoral neck, three had radiolucent zones interpreted as osteolysis, and twenty
      had signs of neck-socket impingement. Five hips had radiolucencies around the
      metaphyseal stem (two partial and three complete) that had been stable for 7.8 to
      10.2 years. The mean scores on the University of California at Los Angeles (UCLA)
      system at the time of the latest follow-up were 9.5 points for pain, 9.3 points
      for walking, 8.9 points for function, and 6.8 points for activity; the mean
      scores on the physical and mental components of the Short Form-12 (SF-12) were
      47.3 and 50.5 points, respectively; and the mean Harris hip score was 90 points.
      CONCLUSIONS: The results of the present series constitute a reference point to
      which subsequent series should be compared. These ten-year results in a group of
      young patients are satisfactory, and the low rate of osteolysis is encouraging,
      but longer follow-up is required for comparison with conventional total hip
      arthroplasty.

PMID- 21084577
TI  - In vivo biological response to vitamin E and vitamin-E-doped polyethylene.
AB  - BACKGROUND: Cross-linking has decreased the wear of ultra-high molecular weight
      polyethylene, a cause of osteolysis leading to total joint replacement failure.
      Compared with melting or annealing, doping cross-linked ultra-high molecular
      weight polyethylene with vitamin E stabilizes free radicals from irradiation
      while maintaining mechanical properties and wear resistance. This study was done
      to determine the local tissue effects of free vitamin E and vitamin E eluted from
      ultra-high molecular weight polyethylene implants in the joint space. METHODS:
      Three studies were performed. First, pure vitamin E and solubilized vitamin E
      were injected into rabbit knees to simulate vitamin-E elution from radiation
      cross-linked ultra-high molecular weight polyethylene; second, vitamin-E-doped,
      irradiated ultra-high molecular weight polyethylene plugs were implanted into
      dorsal subcutaneous pouches of rabbits to determine the local effects of vitamin
      E elution from radiation cross-linked ultra-high molecular weight polyethylene;
      and, third, two groups of vitamin-E-doped, irradiated acetabular liners (high
      surface and uniform vitamin-E concentration profiles) were compared with undoped,
      control ultra-high molecular weight polyethylene liners in a canine model of
      total hip replacement to determine the effect of possible vitamin-E elution on
      bone ingrowth and the local tissue response to it in a load-bearing environment.
      RESULTS: Injection of solubilized vitamin E resulted in histologically normal
      surrounding soft tissue at both two and twelve-week follow-up intervals, while
      injection of pure vitamin E resulted in acute and chronic inflammation at the
      time of the two-week follow-up. Both control and vitamin-E-doped subcutaneous
      plugs showed inflammation associated with surgery at two weeks of follow-up, but
      showed stable fibrous encapsulation without inflammation at twelve weeks of
      follow-up. In the canine total hip replacement model, there was no qualitative
      difference in local tissue appearance and no significant difference in the
      percent bone ingrowth and the percent bone density between the control and
      vitamin-E groups. CONCLUSIONS: These investigations showed that vitamin-E-doped
      ultra-high molecular weight polyethylene plugs and total hip replacement
      components are well tolerated in both a small and a large-animal model with no
      observed adverse effects on the surrounding tissues at twelve weeks of follow-up.

PMID- 21084578
TI  - Local treatment of meniscal lesions with vascular endothelial growth factor.
AB  - BACKGROUND: The healing potential in the avascular regions of the meniscus is
      very limited, and improving the vascularity might be a reasonable way to improve
      healing. Vascular endothelial growth factor (VEGF) is one of the most potent
      proangiogenetic factors. We hypothesized that the local application of VEGF(165)
      would (1) improve the healing of a lesion in the avascular region of the
      meniscus, (2) induce angiogenesis in both the avascular and vascular regions, and
      (3) increase the amounts of VEGF mRNA and VEGF. METHODS: In eighteen sheep, the
      medial menisci were cut longitudinally in the avascular region and were sutured.
      Three groups were established depending on the suture material: (1) uncoated
      Ethibond, (2) Ethibond coated with VEGF(165) and its carrier Poly(D,L-Lactide)
      (PDLLA), and (3) Ethibond coated with PDLLA. The contralateral medial menisci
      served as a control group. Each of the three suture type groups included six
      animals. After eight weeks, the sheep were killed, and the menisci were examined
      macroscopically. Immunohistochemistry of Factor VIII and VEGF and real-time
      reverse-transcription polymerase chain reaction (RT-PCR) of VEGF mRNA were
      performed. Additionally, the VEGF release kinetics from the VEGF/PDLLA-coated
      suture were evaluated in vitro. RESULTS: In this model, VEGF did not improve
      meniscal healing. It did not increase angiogenesis in the avascular or vascular
      region, the VEGF concentration, or the amount of VEGF mRNA. VEGF release from the
      coated suture peaked on Day 3 and was nearly zero on Day 9. CONCLUSIONS: The
      local application of VEGF(165) as eluted from suture did not increase meniscal
      angiogenesis or improve meniscal healing. In addition, there was no effect on the
      amount of VEGF mRNA and VEGF. The VEGF carrier (PDLLA) may have been inadequate
      because of the short duration of VEGF supply.

PMID- 21084579
TI  - Surgical release for posttraumatic loss of elbow flexion.
AB  - BACKGROUND: Several surgical approaches have been suggested for the treatment of
      posttraumatic elbow stiffness; however, the optimal approach to elbows with
      considerable loss of flexion has not been well described. We investigated the
      pathologic lesions causing posttraumatic loss of elbow flexion and analyzed the
      results of surgical release. METHODS: Forty-two patients with <100 degrees  of
      elbow flexion due to an extrinsic contracture following trauma underwent surgical
      release at a median of ten months after injury. To achieve maximum flexion,
      release of the posterior band of the medial collateral ligament was mandatory in
      all patients, and only four patients required additional anterior procedures. The
      ulnar nerve was transposed anteriorly in forty patients, including three who had
      had a previous transposition. To evaluate the results, we compared preoperative
      and postoperative elbow motion, Mayo Elbow Performance Index (MEPI) scores, and
      radiographs. RESULTS: Intraoperatively, heterotopic ossification was observed in
      forty patients. It was located predominantly in the posteromedial aspect of the
      capsule. Heterotopic bone was more commonly found during surgery than it was
      identified preoperatively on radiographs. Mean flexion increased significantly
      from 89 degrees  preoperatively to 124 degrees  (range, 90 degrees  to 140
      degrees ) at a mean of thirty-nine months postoperatively. The mean size of the
      flexion contracture decreased from 34 degrees  preoperatively to 9 degrees 
      (range, 0 degrees  to 30 degrees ) postoperatively. Overall, >=120 degrees  of
      final flexion and a total arc of >=100 degrees  were regained by 88% of the
      patients. The mean MEPI score improved significantly from 73 points
      preoperatively to 94 points (range, 72 to 100 points) postoperatively, with the
      result rated as excellent in thirty-two patients, good in eight, and fair in two.
      Two patients had clinical recurrence of heterotopic ossification associated with
      a failure to obtain an increase in flexion. CONCLUSIONS: This study demonstrates
      that posttraumatic heterotopic ossification, particularly in the posteromedial
      aspect of the capsule, is closely associated with loss of elbow flexion.
      Satisfactory restoration of elbow flexion can be obtained in the majority of
      patients by surgical release of the posterior band of the medial collateral
      ligament and excision of heterotopic bone.

PMID- 21084580
TI  - Effectiveness of the AAOS Leadership Fellows Program for Orthopaedic Surgeons.
AB  - BACKGROUND: Effective physician leadership is critical to the future success of
      healthcare organizations. The American Academy of Orthopaedic Surgeons (AAOS)
      Leadership Fellows Program is a one-year program designed to train young
      orthopaedic surgeons to become future leaders in orthopaedics. The purpose of
      this study was to evaluate the impact of the AAOS Leadership Fellows Program on
      the leadership skills and achievements of its participants. METHODS: Graduates of
      the Leadership Fellows Program were compared with a control group of previous
      applicants who were not accepted to the program (applicants) in a retrospective
      cohort comparison study. A subjective survey of leadership skills was used to
      assess the confidence of the two cohorts in eight areas of leadership. In
      addition, an updated curriculum vitae from each of sixty leadership fellows from
      the classes of 2003 through 2009 and from each of forty-seven applicants was
      retrospectively reviewed for evidence of leadership. The updated curriculum vitae
      of the leadership fellows was evaluated for leadership activity attained prior to
      and following participation in the program, while the updated curriculum vitae of
      applicants was evaluated for leadership activity attained prior to and following
      the last year of application to the program. Curricula vitae were assessed for
      demonstration of national leadership, academic rank, hospital administrative
      rank, and research experience. RESULTS: On the leadership survey, the graduates
      of the Leadership Fellows Program scored higher than the applicants in seven of
      eight categories. The review of the curricula vitae demonstrated that, prior to
      the Leadership Fellows Program, the leadership fellows were more likely than the
      applicants to have an academic practice and hold an academic rank. The difference
      between the two cohorts in administrative rank and leadership of national
      committees was not significant. Following the program, the leadership fellows
      were more likely to chair national committees (p < 0.001) and hold leadership
      positions in their hospitals (p = 0.008). Furthermore, the leadership fellows
      were more likely to advance in their academic and administrative ranks compared
      with those who applied to the program and were not accepted. CONCLUSIONS: The
      AAOS Leadership Fellows Program seems to have a positive impact on the leadership
      competency of its participants. Graduates of the program are more likely to
      assume leadership positions in national organizations and within their own
      institutions.

PMID- 21084581
TI  - Comparison of the outcomes of distraction osteogenesis for first and fourth
      brachymetatarsia.
AB  - BACKGROUND: Brachymetatarsia is the presence of an abnormally short metatarsal,
      and distraction osteogenesis has been used for its treatment. The purpose of the
      present study was to compare the outcomes of patients who underwent distraction
      osteogenesis for the treatment of first and/or fourth brachymetatarsia. METHODS:
      The data from forty-eight patients (sixty-four feet, seventy-four metatarsals)
      who underwent distraction osteogenesis for the treatment of brachymetatarsia were
      reviewed. The indications for surgery included a metatarsal that was at least 10
      mm shorter than the adjacent metatarsal and that had an unacceptable cosmetic
      appearance. The study group comprised thirty-two first brachymetatarsia in
      nineteen patients (Group A) and forty-two fourth brachymetatarsia in twenty-nine
      patients (Group B). The average age was twenty years in Group A and eighteen
      years in Group B. The average duration of follow-up was 58.1 months in Group A
      and 56.1 in Group B. Metatarsal length, lengthening gain, healing time and index,
      and the American Orthopaedic Foot and Ankle Society hallux metatarsophalangeal
      interphalangeal and lesser metatarsophalangeal-interphalangeal scores were
      evaluated. RESULTS: All patients were satisfied with the final length of the
      metatarsal and all had achieved bone union at the time of the last follow-up. The
      mean lengthening gain was 17.2 mm (42.9%) in Group A and 16.3 mm (37.3%) in Group
      B. The mean healing index was 71.0 days/cm in Group A and 67.3 days/cm in Group
      B. The mean American Orthopaedic Foot and Ankle Society score was 91.2 points in
      Group A and 92.8 points in Group B at the last follow-up (twenty-two excellent,
      nine good, and one fair results in Group A, and twenty-nine excellent, eleven
      good, and two fair results in Group B). The most common complication was
      metatarsophalangeal joint stiffness, which occurred in thirteen rays in Group A
      and in twelve rays in Group B; malalignment of the lengthened metatarsal was
      observed six times in each group. No significant intergroup differences in the
      outcomes were found. CONCLUSIONS: Distraction osteogenesis for first and/or
      fourth brachymetatarsia provided successful lengthening of a metatarsal with
      eventual osseous union and was associated with similar outcomes in terms of
      healing index, function score, and the prevalence of complications between the
      two groups, although frequent complications were encountered and no improvement
      in foot function was found.

PMID- 21084582
TI  - Late foreign-body reaction after treatment of distal radial fractures with poly-L
      lactic acid bioabsorbable implants: a report of three cases.

PMID- 21084583
TI  - Isolated cardiac metastasis from a histologically "benign" giant-cell tumor of
      the distal end of the femur: a case report.

PMID- 21084584
TI  - Risk of wound infection is greater after skin closure with staples than with
      sutures in orthopaedic surgery.

PMID- 21084585
TI  - Therapeutic exercises during the first week after ankle sprain improved short
      term ankle function.

PMID- 21084586
TI  - Hip resurfacing was not better than total hip arthroplasty for hip disease.

PMID- 21084587
TI  - Achieving stability and lower-limb length in total hip arthroplasty.

PMID- 21084588
TI  - What's new in adult reconstructive knee surgery.

PMID- 21084589
TI  - Organisational justice and cognitive function in middle-aged employees: the
      Whitehall II study.
AB  - BACKGROUND: Little is known about the role that work-related factors play in the
      decline of cognitive function. This study examined the association between
      perceived organisational justice and cognitive function among middle-aged men and
      women. METHODS: Perceived organisational justice was measured at phases 1 (1985
      8) and 2 (1989-90) of the Whitehall II study when the participants were 35-55
      years old. Assessment of cognitive function at the screening clinic at phases 5
      (1997-9) and 7 (2003-4) included the following tests in the screening clinic:
      memory, inductive reasoning (Alice Heim 4), vocabulary (Mill Hill), and verbal
      fluency (phonemic and semantic). Mean exposure to lower organisational justice at
      phases 1 and 2 in relation to cognitive function at phases 5 and 7 were analysed
      using linear regression analyses. The final sample included 4531 men and women.
      RESULTS: Lower mean levels of justice at phases 1 and 2 were associated with
      worse cognitive function in terms of memory, inductive reasoning, vocabulary and
      verbal fluency at both phases 5 and 7. These associations were independent of
      covariates, such as age, occupational grade, behavioural risks, depression,
      hypertension and job strain. CONCLUSIONS: This study suggests an association
      between perceived organisational justice and cognitive function. Further studies
      are needed to examine whether interventions designed to improve organisational
      justice would affect employees' cognition function favourably.

PMID- 21084590
TI  - No quick fix: understanding the difference between fixed and random effect
      models.

PMID- 21084592
TI  - Three Drosophila liprins interact to control synapse formation.
AB  - Liprin-alpha proteins are adaptors that interact with the receptor protein
      tyrosine phosphatase leukocyte common antigen-related (LAR) and other synaptic
      proteins to promote synaptic partner selection and active zone assembly. Liprin
      beta proteins bind to and share homology with Liprin-alpha proteins, but their
      functions at the synapse are unknown. The Drosophila genome encodes single Liprin
      alpha and Liprin-beta homologs, as well as a third related protein that we named
      Liprin-gamma. We show that both Liprin-beta and Liprin-gamma physically interact
      with Liprin-alpha and that Liprin-gamma also binds to LAR. Liprin-alpha mutations
      have been shown to disrupt synaptic target layer selection by R7 photoreceptors
      and to reduce the size of larval neuromuscular synapses. We have generated null
      mutations in Liprin-beta and Liprin-gamma to investigate their role in these
      processes. We find that, although Liprin-alpha mutant R7 axons terminate before
      reaching the correct target layer, Liprin-beta mutant R7 axons grow beyond their
      target layer. Larval neuromuscular junction size is reduced in both Liprin-alpha
      and Liprin-beta mutants, and further reduced in double mutants, suggesting
      independent functions for these Liprins. Genetic interactions demonstrate that
      both Liprin proteins act through the exchange factor Trio to promote stable
      target selection by R7 photoreceptor axons and growth of neuromuscular synapses.
      Photoreceptor and neuromuscular synapses develop normally in Liprin-gamma
      mutants; however, removing Liprin-gamma improves R7 targeting in Liprin-alpha
      mutants, and restores normal neuromuscular junction size to Liprin-beta mutants,
      suggesting that Liprin-gamma counteracts the functions of the other two Liprins.
      We propose that context-dependent interactions between the three Liprins modulate
      their functions in synapse formation.

PMID- 21084593
TI  - Deletion of CD14 attenuates Alzheimer's disease pathology by influencing the
      brain's inflammatory milieu.
AB  - Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid
      (Abeta)-containing plaques within the brain that is accompanied by a robust
      microglial-mediated inflammatory response. This inflammatory response is reliant
      upon engagement of innate immune signaling pathways involving the toll-like
      receptors (TLRs). Studies assessing the roles of TLRs in AD pathogenesis have
      yielded conflicting results. We have assessed the roles of the TLRs through
      genetic inactivation of the TLR2/4 coreceptor, CD14, in a transgenic murine model
      of AD. Transgenic mice lacking CD14 exhibited reduced insoluble, but not soluble,
      levels of Abeta at 7 months of age. This corresponded with decreased plaque
      burden resulting from a reduction in number and size of both diffuse and
      thioflavin S-positive plaques and an overall reduction in the number of
      microglia. These findings are inconsistent with the established actions of these
      receptors. Moreover, loss of CD14 expression was associated with increased
      expression of genes encoding the proinflammatory cytokines Tnfalpha and Ifngamma,
      decreased levels of the microglial/macrophage alternative activation markers
      Fizz1 and Ym1, and increased expression of the anti-inflammatory gene Il-10.
      Thus, the loss of CD14 resulted in a significant change in the inflammatory
      environment of the brain, likely reflecting a more heterogeneous population of
      microglia within the brains of the animals. The reduction in plaque burden was
      not a result of changes in the expression of various Abeta degrading enzymes or
      proteins associated with Abeta clearance. These data suggest that CD14 is a
      critical regulator of the microglial inflammatory response that acts to modulate
      Abeta deposition.

PMID- 21084594
TI  - Phosphorylation dynamics regulate Hsp27-mediated rescue of neuronal plasticity
      deficits in tau transgenic mice.
AB  - Molecular chaperones regulate the aggregation of a number of proteins that
      pathologically misfold and accumulate in neurodegenerative diseases. Identifying
      ways to manipulate these proteins in disease models is an area of intense
      investigation; however, the translation of these results to the mammalian brain
      has progressed more slowly. In this study, we investigated the ability of one of
      these chaperones, heat shock protein 27 (Hsp27), to modulate tau dynamics.
      Recombinant wild-type Hsp27 and a genetically altered version of Hsp27 that is
      perpetually pseudo-phosphorylated (3*S/D) were generated. Both Hsp27 variants
      interacted with tau, and atomic force microscopy and dynamic light scattering
      showed that both variants also prevented tau filament formation. However,
      extrinsic genetic delivery of these two Hsp27 variants to tau transgenic mice
      using adeno-associated viral particles showed that wild-type Hsp27 reduced
      neuronal tau levels, whereas 3*S/D Hsp27 was associated with increased tau
      levels. Moreover, rapid decay in hippocampal long-term potentiation (LTP)
      intrinsic to this tau transgenic model was rescued by wild-type Hsp27
      overexpression but not by 3*S/D Hsp27. Because the 3*S/D Hsp27 mutant cannot
      cycle between phosphorylated and dephosphorylated states, we can conclude that
      Hsp27 must be functionally dynamic to facilitate tau clearance from the brain and
      rescue LTP; however, when this property is compromised, Hsp27 may actually
      facilitate accumulation of soluble tau intermediates.

PMID- 21084595
TI  - Processing afferent proprioceptive information at the main cuneate nucleus of
      anesthetized cats.
AB  - Medial lemniscal activity decreases before and during movement, suggesting
      prethalamic modulation, but the underlying mechanisms are largely unknown. Here
      we studied the mechanisms underlying proprioceptive transmission at the
      midventral cuneate nucleus (mvCN) of anesthetized cats using standard
      extracellular recordings combined with electrical stimulation and
      microiontophoresis. Dual simultaneous recordings from mvCN and rostroventral
      cuneate (rvCN) proprioceptive neurons demonstrated that microstimulation through
      the rvCN recording electrode induced dual effects on mvCN projection cells:
      potentiation when both neurons had excitatory receptive fields in muscles acting
      at the same joint, and inhibition when rvCN and mvCN cells had receptive fields
      located in different joints. GABA and/or glycine consistently abolished mvCN
      spontaneous and sensory-evoked activity, an effect reversed by bicuculline and
      strychnine, respectively; and immunohistochemistry data revealed that cells
      possessing strychnine-sensitive glycine receptors were uniformly distributed
      throughout the cuneate nucleus. It was also found that proprioceptive mvCN
      projection cells sent ipsilateral collaterals to the nucleus reticularis
      gigantocellularis and the mesencephalic locomotor region, and had slower
      antidromic conduction speeds than cutaneous fibers from the more dorsally located
      cluster region. The data suggest that (1) the rvCN-mvCM network is functionally
      related to joints rather than to single muscles producing an overall potentiation
      of proprioceptive feedback from a moving forelimb joint while inhibiting, through
      GABAergic and glycinergic interneurons, deep muscular feedback from other
      forelimb joints; and (2) mvCN projection cells collateralizing to or through the
      ipsilateral reticular formation allow for bilateral spreading of ascending
      proprioceptive feedback information.

PMID- 21084591
TI  - Metzincin proteases and their inhibitors: foes or friends in nervous system
      physiology?
AB  - Members of the metzincin family of metalloproteinases have long been considered
      merely degradative enzymes for extracellular matrix molecules. Recently, however,
      there has been growing appreciation for these proteinases and their endogenous
      inhibitors, tissue inhibitors of metalloproteinases (TIMPs), as fine modulators
      of nervous system physiology and pathology. Present all along the phylogenetic
      tree, in all neural cell types, from the nucleus to the synapse and in the
      extracellular space, metalloproteinases exhibit a complex spatiotemporal profile
      of expression in the nervous parenchyma and at the neurovascular interface. The
      irreversibility of their proteolytic activity on numerous biofactors (e.g.,
      growth factors, cytokines, receptors, DNA repair enzymes, matrix proteins) is
      ideally suited to sustain structural changes that are involved in physiological
      or postlesion remodeling of neural networks, learning consolidation or
      impairment, neurodegenerative and neuroinflammatory processes, or progression of
      malignant gliomas. The present review provides a state of the art overview of the
      involvement of the metzincin/TIMP system in these processes and the prospects of
      new therapeutic strategies based on the control of metalloproteinase activity.

PMID- 21084596
TI  - Counter-regulation of opioid analgesia by glial-derived bioactive sphingolipids.
AB  - The clinical efficacy of opiates for pain control is severely limited by
      analgesic tolerance and hyperalgesia. Herein we show that chronic morphine
      upregulates both the sphingolipid ceramide in spinal astrocytes and microglia,
      but not neurons, and spinal sphingosine-1-phosphate (S1P), the end-product of
      ceramide metabolism. Coadministering morphine with intrathecal administration of
      pharmacological inhibitors of ceramide and S1P blocked formation of spinal S1P
      and development of hyperalgesia and tolerance in rats. Our results show that
      spinally formed S1P signals at least in part by (1) modulating glial function
      because inhibiting S1P formation blocked increased formation of glial-related
      proinflammatory cytokines, in particular tumor necrosis factor-alpha, interleukin
      1betaalpha, and interleukin-6, which are known modulators of neuronal
      excitability, and (2) peroxynitrite-mediated posttranslational nitration and
      inactivation of glial-related enzymes (glutamine synthetase and the glutamate
      transporter) known to play critical roles in glutamate neurotransmission.
      Inhibitors of the ceramide metabolic pathway may have therapeutic potential as
      adjuncts to opiates in relieving suffering from chronic pain.

PMID- 21084597
TI  - EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after
      transient cerebral ischemia.
AB  - EAAC1 is a neuronal glutamate and cysteine transporter. EAAC1 uptake of cysteine
      provides substrate for neuronal glutathione synthesis, which plays a key role in
      both antioxidant defenses and intracellular zinc binding. Here we evaluated the
      role of EAAC1 in neuronal resistance to ischemia. EAAC1(-/-) mice subjected to
      transient cerebral ischemia exhibited twice as much hippocampal neuronal death as
      wild-type mice and a corresponding increase in microglial activation. EAAC1(-/-)
      mice also had elevated vesicular and cytosolic zinc concentrations in hippocampal
      CA1 neurons and an increased zinc translocation to postsynaptic neurons after
      ischemia. Treatment of the EAAC1(-/-) mice with N-acetyl cysteine restored
      neuronal glutathione concentrations and normalized basal zinc levels in the
      EAAC1(-/-) mice. Treatment of the EAAC1(-/-) mice with either N-acetyl cysteine
      or with zinc chelators reduced ischemia-induced zinc translocation, superoxide
      production, and neuron death. These findings suggest that cysteine uptake by
      EAAC1 is important for zinc homeostasis and neuronal antioxidant function under
      ischemic conditions.

PMID- 21084598
TI  - Low-threshold Ca2+ current amplifies distal dendritic signaling in thalamic
      reticular neurons.
AB  - The low-threshold transient calcium current (I(T)) plays a critical role in
      modulating the firing behavior of thalamic neurons; however, the role of I(T) in
      the integration of afferent information within the thalamus is virtually unknown.
      We have used two-photon laser scanning microscopy coupled with whole-cell
      recordings to examine calcium dynamics in the neurons of the strategically
      located thalamic reticular nucleus (TRN). We now report that a single somatic
      burst discharge evokes large-magnitude calcium responses, via I(T), in distal TRN
      dendrites. The magnitude of the burst-evoked calcium response was larger than
      those observed in thalamocortical projection neurons under the same conditions.
      We also demonstrate that direct stimulation of distal TRN dendrites, via focal
      glutamate application and synaptic activation, can locally activate distal I(T),
      producing a large distal calcium response independent of the soma/proximal
      dendrites. These findings strongly suggest that distally located I(T) may
      function to amplify afferent inputs. Boosting the magnitude ensures integration
      at the somatic level by compensating for attenuation that would normally occur
      attributable to passive cable properties. Considering the functional architecture
      of the TRN, elongated nature of their dendrites, and robust dendritic signaling,
      these distal dendrites could serve as sites of intense intra-modal/cross-modal
      integration and/or top-down modulation, leading to focused thalamocortical
      communication.

PMID- 21084599
TI  - The bone morphogenetic protein roof plate chemorepellent regulates the rate of
      commissural axonal growth.
AB  - Commissural spinal axons extend away from the roof plate (RP) in response to a
      chemorepellent mediated by the bone morphogenetic proteins (BMPs). Previous
      studies have focused on the ability of commissural axons to translate a spatial
      gradient of BMPs into directional information in vitro. However, a notable
      feature of this system in vivo is that the gradient of BMPs is thought to act
      from behind the commissural cell bodies, making it possible for the BMPs to have
      a continued effect on commissural axons as they grow away from the RP. Here, we
      demonstrate that BMPs activate the cofilin regulator Lim domain kinase 1 (Limk1)
      to control the rate of commissural axon extension in the dorsal spinal cord. By
      modulating Limk1 activity in both rodent and chicken commissural neurons, the
      rate of axon growth can either be stalled or accelerated. Altering the activation
      state of Limk1 also influences subsequent guidance decisions: accelerated axons
      make rostrocaudal projection errors while navigating their intermediate target,
      the floor plate. These results suggest that guidance cues can specify information
      about the rate of growth, to ensure that axons reach subsequent signals either at
      particular times or speeds during development.

PMID- 21084600
TI  - Field potential signature of distinct multicellular activity patterns in the
      mouse hippocampus.
AB  - Cognitive functions go along with complex patterns of distributed activity in
      neuronal networks, thereby forming assemblies of selected neurons. To support
      memory processes, such assemblies have to be stabilized and reactivated in a
      highly reproducible way. The rodent hippocampus provides a well studied model
      system for network mechanisms underlying spatial memory formation. Assemblies of
      place-encoding cells are repeatedly activated during sleep-associated network
      states called sharp wave-ripple complexes (SPW-Rs). Behavioral studies suggest
      that at any time the hippocampus harbors a limited number of different assemblies
      that are transiently stabilized for memory consolidation. We hypothesized that
      the corresponding field potentials (sharp wave-ripple complexes) contain a
      specific signature of the underlying neuronal activity patterns. Hence, they
      should fall into a limited number of different waveforms. Application of unbiased
      sorting algorithms to sharp wave-ripple complexes in mouse hippocampal slices did
      indeed reveal the reliable recurrence of defined waveforms that were robust over
      prolonged recording periods. Single-unit discharges tended to fire selectively
      with certain SPW-R classes and were coupled above chance level. Thus, field SPW
      Rs of different waveforms are directly related to the underlying multicellular
      activity patterns that recur with high fidelity. This direct relationship between
      the coordinated activity of distinct groups of neurons and macroscopic
      electrographic signals may be important for cognition-related physiological
      studies in humans and behaving animals.

PMID- 21084601
TI  - Ventrolateral prefrontal cortex plays an executive regulation role in
      comprehension of abstract words: convergent neuropsychological and repetitive TMS
      evidence.
AB  - Neuroimaging studies reliably reveal ventrolateral prefrontal cortex (VLPFC)
      activation for processing of abstract relative to concrete words, but the cause
      of this effect is unclear. Here, in a convergent neuropsychological and
      repetitive transcranial magnetic stimulation (rTMS) investigation, we tested the
      hypothesis that abstract words require VLPFC because they depend heavily on the
      semantic-executive control processes mediated by this region. Specifically, we
      hypothesized that accessing the meanings of abstract words require more executive
      regulation because they have variable, context-dependent meanings. In the
      neuropsychology component of the study, aphasic patients with multimodal semantic
      deficits following VLPFC lesions had impaired comprehension of abstract words,
      but this deficit was ameliorated by providing a sentence cue that placed the word
      in a specific context. Concrete words were better comprehended and showed more
      limited benefit from the cues. In the second part of the study, rTMS applied to
      left VLPFC in healthy subjects slowed reaction times to abstract but not concrete
      words, but only when words were presented out of context. TMS had no effect when
      words were preceded by a contextual cue. These converging results indicate that
      VLPFC plays an executive regulation role in the processing of abstract words.
      This role is less critical when words are presented with a context that guides
      the system toward a particular meaning or interpretation. Regulation is less
      important for concrete words because their meanings are constrained by their
      physical referents and do not tend to vary with context.

PMID- 21084602
TI  - Shift from goal-directed to habitual cocaine seeking after prolonged experience
      in rats.
AB  - The development of drug-seeking habits is implicated in the transition from
      recreational drug use to addiction. Using a drug seeking/taking chained schedule
      of intravenous cocaine self-administration and reward devaluation methods in
      rats, the present studies examined whether drug seeking that is initially goal
      directed becomes habitual after prolonged drug seeking and taking. Devaluation of
      the outcome of the drug seeking link (i.e., the drug taking link of the chained
      schedule) by extinction significantly decreased drug seeking indicating that
      behavior is goal-directed rather than habitual. With, however, more prolonged
      drug experience, animals transitioned to habitual cocaine seeking. Thus, in these
      animals, cocaine seeking was insensitive to outcome devaluation. Moreover, when
      the dorsolateral striatum, an area implicated in habit learning, was transiently
      inactivated, outcome devaluation was effective in decreasing drug seeking
      indicating that responding was no longer habitual but had reverted to control by
      the goal-directed system. These studies provide direct evidence that cocaine
      seeking becomes habitual with prolonged drug experience and describe a rodent
      model with which to study the neural mechanisms underlying the transition from
      goal-directed to habitual drug seeking.

PMID- 21084603
TI  - Subcellular profiling reveals distinct and developmentally regulated repertoire
      of growth cone mRNAs.
AB  - Cue-directed axon guidance depends partly on local translation in growth cones.
      Many mRNA transcripts are known to reside in developing axons, yet little is
      known about their subcellular distribution or, specifically, which transcripts
      are in growth cones. Here laser capture microdissection (LCM) was used to isolate
      the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species,
      mouse and Xenopus, coupled with unbiased genomewide microarray profiling. An
      unexpectedly large pool of mRNAs defined predominant pathways in protein
      synthesis, oxidative phosphorylation, cancer, neurological disease, and
      signaling. Comparative profiling of "young" (pathfinding) versus "old" (target
      arriving) Xenopus growth cones revealed that the number and complexity of
      transcripts increases dramatically with age. Many presynaptic protein mRNAs are
      present exclusively in old growth cones, suggesting that functionally related
      sets of mRNAs are targeted to growth cones in a developmentally regulated way.
      Remarkably, a subset of mRNAs was significantly enriched in the growth cone
      compared with the axon compartment, indicating that mechanisms exist to localize
      mRNAs selectively to the growth cone. Furthermore, some receptor transcripts
      (e.g., EphB4), present exclusively in old growth cones, were equally abundant in
      young and old cell bodies, indicating that RNA trafficking from the soma is
      developmentally regulated. Our findings show that the mRNA repertoire in growth
      cones is regulated dynamically with age and suggest that mRNA localization is
      tailored to match the functional demands of the growing axon tip as it transforms
      into the presynaptic terminal.

PMID- 21084604
TI  - Presynaptic resurgent Na+ currents sculpt the action potential waveform and
      increase firing reliability at a CNS nerve terminal.
AB  - Axonal and nerve terminal action potentials often display a depolarizing after
      potential (DAP). However, the underlying mechanism that generates the DAP, and
      its impact on firing patterns, are poorly understood at axon terminals. Here, we
      find that at calyx of Held nerve terminals in the rat auditory brainstem the DAP
      is blocked by low doses of externally applied TTX or by the internal dialysis of
      low doses of lidocaine analog QX-314. The DAP is thus generated by a voltage
      dependent Na(+) conductance present after the action potential spike. Voltage
      clamp recordings from the calyx terminal revealed the expression of a resurgent
      Na(+) current (I(NaR)), the amplitude of which increased during early postnatal
      development. The calyx of Held also expresses a persistent Na(+) current
      (I(NaP)), but measurements of calyx I(NaP) together with computer modeling
      indicate that the fast deactivation time constant of I(NaP) minimizes its
      contribution to the DAP. I(NaP) is thus neither sufficient nor necessary to
      generate the calyx DAP, whereas I(NaR) by itself can generate a prominent DAP.
      Dialysis of a small peptide fragment of the auxiliary beta4 Na(+) channel subunit
      into immature calyces (postnatal day 5-6) induced an increase in I(NaR) and a
      larger DAP amplitude, and enhanced the spike-firing precision and reliability of
      the calyx terminal. Our results thus suggest that an increase of I(NaR) during
      postnatal synaptic maturation is a critical feature that promotes precise and
      resilient high-frequency firing.

PMID- 21084605
TI  - The selectivity of neurons in the macaque fundus of the superior temporal area
      for three-dimensional structure from motion.
AB  - Motion is a potent cue for the perception of three-dimensional (3D) shape in
      primates, but little is known about its underlying neural mechanisms. Guided by
      recent functional magnetic resonance imaging results, we tested neurons in the
      fundus of the superior temporal sulcus (FST) area of two macaque monkeys (Macaca
      mulatta, one male) using motion-defined surface patches with various 3D shapes
      such as slanted planes, saddles, or cylinders. The majority of the FST neurons
      (>80%) were selective for stimuli depicting specific shapes, and all the surfaces
      tested were represented among the selective FST neurons. Importantly, this
      selectivity tolerated changes in speed, position, size, or between binocular and
      monocular presentations. This tolerance demonstrates that the 3D structure-from
      motion (3D-SFM) selectivity of FST neurons is a higher-order selectivity, which
      cannot be reduced to a lower-order speed selectivity. The 3D-SFM selectivity of
      FST neurons was unaffected by removal of the opposed-motion cue that supplemented
      the speed gradient cue in the standard stimuli. When tested with the same
      standard stimuli, fewer neurons in the middle temporal/visual 5 (MT/V5) area were
      selective than FST neurons. In addition, selective MT/V5 neurons represented
      fewer types of surfaces and were less tolerant of stimulus changes than FST
      neurons. Overall, these results indicate that FST neurons code motion-defined 3D
      shape fragments, underscoring the central role of FST in processing 3D-SFM.

PMID- 21084606
TI  - Exploiting development to evaluate auditory encoding of amplitude modulation.
AB  - During development, detection for many percepts matures gradually. This provides
      a natural system in which to investigate the neural mechanisms underlying
      performance differences: those aspects of neural activity that mature in
      conjunction with behavioral performance are more likely to subserve detection. In
      principle, the limitations on performance could be attributable to either
      immature sensory encoding mechanisms or an immature decoding of an already-mature
      sensory representation. To evaluate these alternatives in awake gerbil auditory
      cortex, we measured neural detection of sinusoidally amplitude-modulated (sAM)
      stimuli, for which behavioral detection thresholds display a prolonged
      maturation. A comparison of single-unit responses in juveniles and adults
      revealed that encoding of static tones was adult like in juveniles, but responses
      to sAM depth were immature. Since perceptual performance may reflect the activity
      of an animal's most sensitive neurons, we analyzed the d prime curves of single
      neurons and found an equivalent percentage with highly sensitive thresholds in
      juvenile and adult animals. In contrast, perceptual performance may reflect the
      pooling of information from neurons with a range of sensitivities. We evaluated a
      pooling model that assumes convergence of a population of inputs at a downstream
      target neuron and found poorer sAM detection thresholds for juveniles. Thus, if
      sAM detection is based on the most sensitive neurons, then immature behavioral
      performance is best explained by an immature decoding mechanism. However, if sAM
      detection is based on a population response, then immature detection thresholds
      are more likely caused by an inadequate sensory representation.

PMID- 21084609
TI  - Motor and dorsal root ganglion axons serve as choice points for the ipsilateral
      turning of dI3 axons.
AB  - The axons of the spinal intersegmental interneurons are projected longitudinally
      along various funiculi arrayed along the dorsal-ventral axis of the spinal cord.
      The roof plate and the floor plate have a profound role in patterning their
      initial axonal trajectory. However, other positional cues may guide the final
      architecture of interneuron tracks in the spinal cord. To gain more insight into
      the organization of specific axonal tracks in the spinal cord, we focused on the
      trajectory pattern of a genetically defined neuronal population, dI3 neurons, in
      the chick spinal cord. Exploitation of newly characterized enhancer elements
      allowed specific labeling of dI3 neurons and axons. dI3 axons are projected
      ipsilaterally along two longitudinal fascicules at the ventral lateral funiculus
      (VLF) and the dorsal funiculus (DF). dI3 axons change their trajectory plane from
      the transverse to the longitudinal axis at two novel checkpoints. The axons that
      elongate at the DF turn at the dorsal root entry zone, along the axons of the
      dorsal root ganglion (DRG) neurons, and the axons that elongate at the VLF turn
      along the axons of motor neurons. Loss and gain of function of the Lim-HD protein
      Isl1 demonstrate that Isl1 is not required for dI3 cell fate. However, Isl1 is
      sufficient to impose ipsilateral turning along the motor axons when expressed
      ectopically in the commissural dI1 neurons. The axonal patterning of dI3 neurons,
      revealed in this study, highlights the role of established axonal cues-the DRG
      and motor axons-as intermediate guidepost cues for dI3 axons.

PMID- 21084608
TI  - Strengthening of top-down frontal cognitive control networks underlying the
      development of inhibitory control: a functional magnetic resonance imaging
      effective connectivity study.
AB  - The ability to voluntarily inhibit responses to task-irrelevant stimuli, which is
      a fundamental component of cognitive control, has a protracted development
      through adolescence. Previous human developmental imaging studies have found
      immaturities in localized brain activity in children and adolescents. However,
      little is known about how these regions integrate with age to form the
      distributed networks known to support cognitive control. In the present study, we
      used Granger causality analysis to characterize developmental changes in
      effective connectivity underlying inhibitory control (antisaccade task) compared
      with reflexive responses (prosaccade task) in human participants. By childhood,
      few top-down connectivities were evident with increased parietal
      interconnectivity. By adolescence, connections from prefrontal cortex increased
      and parietal interconnectivity decreased. From adolescence to adulthood, there
      was evidence of increased number and strength of frontal connections to cortical
      regions as well as subcortical regions. Together, results suggest that
      developmental improvements in inhibitory control may be supported by age-related
      enhancements in top-down effective connectivity between frontal, oculomotor, and
      subcortical regions.

PMID- 21084607
TI  - Protein S protects neurons from excitotoxic injury by activating the TAM receptor
      Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding
      globulin-like region.
AB  - The anticoagulant factor protein S (PS) protects neurons from hypoxic/ischemic
      injury. However, molecular mechanisms mediating PS protection in injured neurons
      remain unknown. Here, we show mouse recombinant PS protects dose-dependently
      mouse cortical neurons from excitotoxic NMDA-mediated neuritic bead formation and
      apoptosis by activating the phosphatidylinositol 3-kinase (PI3K)-Akt pathway
      (EC(50) = 26 +/- 4 nm). PS stimulated phosphorylation of Bad and Mdm2, two
      downstream targets of Akt, which in neurons subjected to pathological
      overstimulation of NMDA receptors (NMDARs) increased the antiapoptotic Bcl-2 and
      Bcl-X(L) levels and reduced the proapoptotic p53 and Bax levels. Adenoviral
      transduction with a kinase-deficient Akt mutant (Ad.Akt(K179A)) resulted in loss
      of PS-mediated neuronal protection, Akt activation, and Bad and Mdm2
      phosphorylation. Using the TAM receptors tyrosine kinases Tyro3-, Axl-, and Mer
      deficient neurons, we showed that PS protected neurons lacking Axl and Mer, but
      not Tyro3, suggesting a requirement of Tyro3 for PS-mediated protection.
      Consistent with these results, PS dose-dependently phosphorylated Tyro3 on
      neurons (EC(50) = 25 +/- 3 nm). In an in vivo model of NMDA-induced excitotoxic
      lesions in the striatum, PS dose-dependently reduced the lesion volume in control
      mice (EC(50) = 22 +/- 2 nm) and protected Axl(-/-) and Mer(-/-) transgenic mice,
      but not Tyro3(-/-) transgenic mice. Using different structural PS analogs, we
      demonstrated that the C terminus sex hormone-binding globulin-like (SHBG) domain
      of PS is critical for neuronal protection in vitro and in vivo. Thus, our data
      show that PS protects neurons by activating the Tyro3-PI3K-Akt pathway via its
      SHGB domain, suggesting potentially a novel neuroprotective approach for acute
      brain injury and chronic neurodegenerative disorders associated with excessive
      activation of NMDARs.

PMID- 21084610
TI  - Prefrontal and medial temporal lobe activity at encoding predicts temporal
      context memory.
AB  - One of the defining features of episodic long-term memory is that it includes
      information about the temporal context in which an event occurred. Little is
      known about the regions that support the encoding of temporal information in the
      human brain, although previous work has suggested a role for the lateral
      prefrontal cortex (PFC) and medial temporal lobes (MTL). Here we used event
      related fMRI to examine the relationship between activity at encoding and
      subsequent memory for temporal context. Participants were scanned while
      performing a serial order working memory task with pictures of common objects and
      were later tested for temporal memory at two different timescales. In the coarse
      temporal memory test, participants viewed one object from each trial and
      indicated approximately when during the course of the experiment it had appeared.
      In the fine temporal memory test, participants were shown the remaining objects
      from each trial and asked to recall the order in which they had been originally
      presented. Activity in the parahippocampal cortex predicted subsequent fine
      temporal accuracy, whereas coarse temporal accuracy was predicted by activity in
      several regions of the PFC, as well as in the hippocampus. Additional multivoxel
      pattern analyses revealed evidence implicating the rostrolateral PFC in the
      representation of time-varying contextual states in a manner similar to that
      proposed by computational theories of temporal context memory. These results
      highlight MTL and PFC contributions to temporal memory at the time of encoding
      and suggest a particular role for the rostrolateral PFC in encoding coarse
      temporal context.

PMID- 21084611
TI  - A robust and biologically plausible spike pattern recognition network.
AB  - The neural mechanisms that enable recognition of spiking patterns in the brain
      are currently unknown. This is especially relevant in sensory systems, in which
      the brain has to detect such patterns and recognize relevant stimuli by
      processing peripheral inputs; in particular, it is unclear how sensory systems
      can recognize time-varying stimuli by processing spiking activity. Because
      auditory stimuli are represented by time-varying fluctuations in frequency
      content, it is useful to consider how such stimuli can be recognized by neural
      processing. Previous models for sound recognition have used preprocessed or low
      level auditory signals as input, but complex natural sounds such as speech are
      thought to be processed in auditory cortex, and brain regions involved in object
      recognition in general must deal with the natural variability present in spike
      trains. Thus, we used neural recordings to investigate how a spike pattern
      recognition system could deal with the intrinsic variability and diverse response
      properties of cortical spike trains. We propose a biologically plausible
      computational spike pattern recognition model that uses an excitatory chain of
      neurons to spatially preserve the temporal representation of the spike pattern.
      Using a single neural recording as input, the model can be trained using a spike
      timing-dependent plasticity-based learning rule to recognize neural responses to
      20 different bird songs with >98% accuracy and can be stimulated to evoke reverse
      spike pattern playback. Although we test spike train recognition performance in
      an auditory task, this model can be applied to recognize sufficiently reliable
      spike patterns from any neuronal system.

PMID- 21084612
TI  - Acute inhibition of PKA activity at old ages ameliorates age-related memory
      impairment in Drosophila.
AB  - Age-related memory impairment (AMI) is a critical and debilitating phenotype of
      brain aging, but its underlying molecular mechanisms are largely unknown. In
      Drosophila, AMI is highly correlated with PKA activity in the mushroom bodies,
      neural centers essential for forming associative olfactory memories. Heterozygous
      mutations in DC0 (DC0/+), which encodes the major catalytic subunit of PKA
      (PKAc), significantly suppress AMI, while overexpression of a DC0 transgene
      (DC0(+)) impairs memory and occludes AMI. PKA activity does not increase upon
      aging, and it is not clear whether AMI is caused by continual PKA activity
      throughout aging or by an acute increase in PKA signaling at old ages. Likewise,
      it is not clear whether AMI can be ameliorated by acute interventions at old ages
      or whether continuous intervention throughout aging is necessary. We show here
      that an acute increase in PKA activity at old ages is sufficient to restore
      normal AMI in DC0/+ flies. Conversely, acute expression of a PKA inhibitory
      peptide at old ages is sufficient to reverse AMI in a wild-type background. These
      results indicate that AMI in Drosophila is caused by an age-dependent change in
      PKA-dependent signaling that can be reversed by acute interventions at old ages.

PMID- 21084613
TI  - Lower-frequency event-related desynchronization: a signature of late mismatch
      responses to sounds, which is reduced or absent in children with specific
      language impairment.
AB  - Poor discrimination of nonlinguistic sounds has been implicated in language
      learning problems in children, but research evidence has been inconsistent. This
      study included 32 participants with specific language impairment (SLI) and 32
      typically developing controls aged 7-16 years. Frequency discrimination
      thresholds were estimated in a task where participants had to distinguish a
      higher-frequency tone from a 1000 Hz tone. Neurophysiological responses were
      assessed in an oddball paradigm. Stimuli were either 1030 or 1200 Hz pure tones
      (deviants) presented in a series of standard 1000 Hz tones, or syllables (deviant
      [da] or [bi] in a series of standard /ba/). On the behavioral task, children (7-
      to 11-year-olds) had high thresholds, regardless of language status, but
      teenagers (12-16 years) with SLI had higher thresholds than their controls.
      Conventional analysis of electrophysiological responses showed no difference
      between groups for the mismatch negativity (MMN), but the late discriminative
      negativity (LDN) was reduced in amplitude for smaller deviants in participants
      with SLI. Time-frequency analysis revealed that, whereas the MMN reflected
      enhanced intertrial coherence in the theta frequency band, the LDN corresponded
      to a period of event-related desynchronization extending across a wide low
      frequency band including delta, theta, and alpha. This manifested as a drop in
      power in those frequencies, which was marked in the controls but reduced or
      absent in children with SLI across all stimulus types. This provides compelling
      evidence for a low-level auditory perceptual impairment in SLI that affects a
      processing stage after initial detection of a sound change.

PMID- 21084614
TI  - Orexin/hypocretin modulates response of ventral tegmental dopamine neurons to
      prefrontal activation: diurnal influences.
AB  - Recent studies show that glutamate and orexin (ORX, also known as hypocretin)
      inputs to the ventral tegmental area (VTA) dopamine (DA) cell region are
      essential for conditioned behavioral responses to reward-associated stimuli. In
      vitro experiments showed that ORX inputs to VTA potentiate responses of DA
      neurons to glutamate inputs, but it has remained unclear which glutamate inputs
      are modulated by ORX. The medial prefrontal cortex (mPFC) is a good candidate,
      given its role in processing complex stimulus-response information and its
      reciprocal connections with VTA DA neurons. Here we used in vivo recordings in
      anesthetized rats to investigate the responses of VTA DA neurons to mPFC
      stimulation, and how these responses are modulated by ORX. We demonstrate that
      mPFC stimulation evokes short- and long-latency excitation and inhibition in DA
      neurons. Maximal short-latency excitatory responses originated from stimulation
      sites in ventral prelimbic/infralimbic cortex, and were significantly more
      frequent during the active than during the rest period of the diurnal cycle.
      Application of ORX onto VTA DA neurons increased baseline activity and augmented
      or revealed excitatory responses to mPFC stimulation independent of changes in
      baseline activity, and without consistently affecting inhibitory responses.
      Moreover, orexin-1 receptor antagonism decreased tonic DA cell activity in active
      but not rest-period animals, confirming a diurnal influence of ORX. These
      results indicate that ORX potently influences DA neuron activity, in part by
      modulating responses to mPFC inputs. By regulating prefrontal control of DA
      release, ORX projections to VTA may shape motivated behaviors in response to
      conditioned stimuli.

PMID- 21084615
TI  - Punishing an error improves learning: the influence of punishment magnitude on
      error-related neural activity and subsequent learning.
AB  - Punishing an error to shape subsequent performance is a major tenet of individual
      and societal level behavioral interventions. Recent work examining error-related
      neural activity has identified that the magnitude of activity in the posterior
      medial frontal cortex (pMFC) is predictive of learning from an error, whereby
      greater activity in this region predicts adaptive changes in future cognitive
      performance. It remains unclear how punishment influences error-related neural
      mechanisms to effect behavior change, particularly in key regions such as pMFC,
      which previous work has demonstrated to be insensitive to punishment. Using an
      associative learning task that provided monetary reward and punishment for recall
      performance, we observed that when recall errors were categorized by subsequent
      performance--whether the failure to accurately recall a number-location
      association was corrected at the next presentation of the same trial--the
      magnitude of error-related pMFC activity predicted future correction. However,
      the pMFC region was insensitive to the magnitude of punishment an error received
      and it was the left insula cortex that predicted learning from the most aversive
      outcomes. These findings add further evidence to the hypothesis that error
      related pMFC activity may reflect more than a prediction error in representing
      the value of an outcome. The novel role identified here for the insular cortex in
      learning from punishment appears particularly compelling for our understanding of
      psychiatric and neurologic conditions that feature both insular cortex
      dysfunction and a diminished capacity for learning from negative feedback or
      punishment.

PMID- 21084616
TI  - ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in
      brain neurons.
AB  - Proneurotrophins and mature neurotrophins activate different signaling pathways
      with distinct effects on their target cells: proneurotrophins can induce
      apoptotic signaling via p75(NTR), whereas mature neurotrophins activate Trk
      receptors to influence survival and differentiation. Here, we demonstrate that
      the PTEN (phosphatase and tensin homolog deleted on chromosome 10) phosphatase
      represents a novel switch between the survival and apoptotic signaling pathways
      in rat CNS neurons. Simultaneous activation of p75(NTR) by proNGF and TrkB
      signaling by BDNF elicited apoptosis despite TrkB phosphorylation. Apoptosis
      induced by p75(NTR) required suppression of TrkB-induced phosphoinositide-3
      kinase signaling, mediated by induction of PTEN, for apoptosis to proceed.
      Inhibition of PTEN restored the ability of BDNF to phosphorylate Akt and protect
      cultured basal forebrain neurons from proNGF-induced death. In vivo, inhibition
      or knockdown of PTEN after pilocarpine-induced seizures protected CNS neurons
      from p75(NTR)-mediated death, demonstrating that PTEN is a crucial factor
      mediating the balance between p75(NTR)-induced apoptotic signaling and Trk
      mediated survival signaling in brain neurons.

PMID- 21084617
TI  - Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the
      hippocampus of a mouse model of fragile X syndrome.
AB  - Fragile X syndrome (FXS) is caused by loss of the FMR1 gene product FMRP (fragile
      X mental retardation protein), a repressor of mRNA translation. According to the
      metabotropic glutamate receptor (mGluR) theory of FXS, excessive protein
      synthesis downstream of mGluR5 activation causes the synaptic pathophysiology
      that underlies multiple aspects of FXS. Here, we use an in vitro assay of protein
      synthesis in the hippocampus of male Fmr1 knock-out (KO) mice to explore the
      molecular mechanisms involved in this core biochemical phenotype under conditions
      where aberrant synaptic physiology has been observed. We find that elevated basal
      protein synthesis in Fmr1 KO mice is selectively reduced to wild-type levels by
      acute inhibition of mGluR5 or ERK1/2, but not by inhibition of mTOR (mammalian
      target of rapamycin). The mGluR5-ERK1/2 pathway is not constitutively overactive
      in the Fmr1 KO, however, suggesting that mRNA translation is hypersensitive to
      basal ERK1/2 activation in the absence of FMRP. We find that hypersensitivity to
      ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility
      in the Fmr1 KO. These results suggest that the ERK1/2 pathway, and other
      neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent
      additional therapeutic targets for FXS.

PMID- 21084618
TI  - Control of CA3 output by feedforward inhibition despite developmental changes in
      the excitation-inhibition balance.
AB  - In somatosensory cortex, the relative balance of excitation and inhibition
      determines how effectively feedforward inhibition enforces the temporal fidelity
      of action potentials. Within the CA3 region of the hippocampus, glutamatergic
      mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong
      monosynaptic excitation that exhibit prominent facilitation during repetitive
      activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs
      facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In
      contrast, in young adult mice this MF-driven polysynaptic inhibitory input can
      facilitate or depress in response to short trains of activity. Transgenic mice
      lacking the feedback inhibitory loop continue to exhibit both facilitating and
      depressing polysynaptic IPSCs, indicating that this robust inhibition is not
      caused by the secondary engagement of feedback inhibition. Surprisingly,
      eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A)
      receptors did not lead to a loss of temporal precision of the first action
      potential observed after a stimulus but triggered in many cases a long excitatory
      plateau potential capable of triggering repetitive action potential firing. These
      observations indicate that, unlike other regions of the brain, the temporal
      precision of single MF-driven action potentials is dictated primarily by the
      kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition
      provides a robust regulation of CA3 PC excitability across development to prevent
      excessive depolarization by the monosynaptic EPSP and multiple action potential
      firings.

PMID- 21084619
TI  - Spontaneous network events driven by depolarizing GABA action in neonatal
      hippocampal slices are not attributable to deficient mitochondrial energy
      metabolism.
AB  - In two recent papers (Rheims et al., 2009; Holmgren et al., 2010), Zilberter and
      coworkers argue that the well known depolarizing GABA actions that take place at
      the cellular and network level in the neonatal hippocampus and neocortex in vitro
      are pathophysiological phenomena, attributable to deficient mitochondrial energy
      metabolism. In their experiments, supplementing the glucose-containing solution
      with weak-acid substrates of mitochondrial energy metabolism (such as beta
      hydroxy-butyrate, lactate, or pyruvate) abolished the spontaneous network events
      (giant depolarizing potentials; GDPs) and the underlying depolarizing actions of
      GABA. In this study, we made electrophysiological recordings of GDPs and
      monitored the mitochondrial membrane potential (Psim) and intracellular pH
      (pH(i)) in CA3 neurons in neonatal rat hippocampal slices. Supplementing the
      standard physiological solution with l-lactate did not produce a change in Psim,
      whereas withdrawal of glucose, in the presence or absence of l-lactate, was
      followed by a pronounced depolarization of Psim. Furthermore, d-lactate (a poor
      substrate of mitochondrial metabolism) caused a prompt inhibition in GDP
      frequency which was similar to the effect of l-lactate. The suppression of GDPs
      was strictly proportional to the fall in pH(i) caused by weak carboxylic acids (l
      lactate, d-lactate, or propionate) or by an elevated CO(2). The main conclusions
      of our work are that the inhibitory effect of l-lactate on GDPs is not mediated
      by mitochondrial energy metabolism, and that glucose at its standard 10 mm
      concentration is an adequate energy substrate for neonatal neurons in vitro.
      Notably, changes in pH(i) appear to have a very powerful modulatory effect on
      GDPs.

PMID- 21084620
TI  - Decision processes in human performance monitoring.
AB  - The ability to detect and compensate for errors is crucial in producing
      effective, goal-directed behavior. Human error processing is reflected in two
      event-related brain potential components, the error-related negativity (Ne/ERN)
      and error positivity (Pe), but the functional significance of both components
      remains unclear. Our approach was to consider error detection as a decision
      process involving an evaluation of available evidence that an error has occurred
      against an internal criterion. This framework distinguishes two fundamental
      stages of error detection--accumulating evidence (input), and reaching a decision
      (output)--that should be differentially affected by changes in internal
      criterion. Predictions from this model were tested in a brightness discrimination
      task that required human participants to signal their errors, with incentives
      varied to encourage participants to adopt a high or low criterion for signaling
      their errors. Whereas the Ne/ERN was unaffected by this manipulation, the Pe
      varied consistently with criterion: A higher criterion was associated with larger
      Pe amplitude for signaled errors, suggesting that the Pe reflects the strength of
      accumulated evidence. Across participants, Pe amplitude was predictive of changes
      in behavioral criterion as estimated through signal detection theory analysis.
      Within participants, Pe amplitude could be estimated robustly with multivariate
      machine learning techniques and used to predict error signaling behavior both at
      the level of error signaling frequencies and at the level of individual signaling
      responses. These results suggest that the Pe, rather than the Ne/ERN, is closely
      related to error detection, and specifically reflects the accumulated evidence
      that an error has been committed.

PMID- 21084621
TI  - Long-distance axon regeneration in the mature optic nerve: contributions of
      oncomodulin, cAMP, and pten gene deletion.
AB  - The inability of retinal ganglion cells (RGCs) to regenerate damaged axons
      through the optic nerve has dire consequences for victims of traumatic nerve
      injury and certain neurodegenerative diseases. Several strategies have been shown
      to induce appreciable regeneration in vivo, but the regrowth of axons through the
      entire optic nerve and on into the brain remains a major challenge. We show here
      that the induction of a controlled inflammatory response in the eye, when
      combined with elevation of intracellular cAMP and deletion of the gene encoding
      pten (phosphatase and tensin homolog), enables RGCs to regenerate axons the full
      length of the optic nerve in mature mice; approximately half of these axons cross
      the chiasm, and a rare subset (~1%) manages to enter the thalamus. Consistent
      with our previous findings, the axon-promoting effects of inflammation were shown
      to require the macrophage-derived growth factor Oncomodulin (Ocm). Elevation of
      cAMP increased the ability of Ocm to bind to its receptors in the inner retina
      and augmented inflammation-induced regeneration twofold. Inflammation combined
      with elevated cAMP and PTEN deletion increased activation of the
      phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling
      pathways and augmented regeneration ~10-fold over the level induced by either
      pten deletion or Zymosan alone. Thus, treatments that synergistically alter the
      intrinsic growth state of RGCs produce unprecedented levels of axon regeneration
      in the optic nerve, a CNS pathway long believed to be incapable of supporting
      such growth.

PMID- 21084622
TI  - Orientation selectivity in rabbit retinal ganglion cells is mediated by
      presynaptic inhibition.
AB  - Cells sensitive to the orientation of edges are ubiquitous in visual systems, and
      have been described in the vertebrate retina, yet the synaptic mechanisms that
      generate orientation selectivity in the retina are largely unknown. Here, we
      analyze the synaptic mechanisms that generate selective responses to vertically
      and horizontally oriented stimuli in rabbit retinal ganglion cells. The data
      indicate that the excitatory and inhibitory inputs to orientation-selective
      ganglion cells are rendered orientation selective within the presynaptic
      circuitry. In accordance with previous extracellular recordings, presynaptic
      GABAergic inhibition is critical to generate orientation selectivity, and we show
      that it includes lateral inhibition of glutamatergic bipolar cells and serial
      inhibitory connections between GABAergic and glycinergic amacrine cells. Despite
      very similar spiking properties, vertically and horizontally selective ganglion
      cells (VS-GCs and HS-GCs, respectively) show marked differences in their
      underlying synaptic mechanisms. Both cell types receive glutamatergic inputs via
      non-NMDA (AMPA/kainate) and NMDA receptors, while VS-GCs receive additional
      excitation mediated by glycinergic disinhibition. A striking difference between
      these cells is that during nonpreferred simulation, excitation is suppressed and
      direct glycinergic inhibition is increased in HS-GCs, whereas for VS-GCs, both
      excitatory and inhibitory inputs are suppressed. Thus, orientation selectivity is
      generated presynaptically both by modulation of bipolar cell output and by serial
      inhibitory connections between amacrine cells. Minimal circuit models are
      proposed that account for these observations.

PMID- 21084623
TI  - Identification of NEEP21 as a beta-amyloid precursor protein-interacting protein
      in vivo that modulates amyloidogenic processing in vitro.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease and the most
      common form of dementia. AD is pathologically characterized by the deposition of
      pathogenic Abeta peptides that are derived from larger integral membrane
      proteins, termed beta-amyloid precursor proteins (APPs). In an attempt to
      understand the function of APP, in vitro studies have focused on the
      identification of interacting proteins. To investigate the APP in vivo
      interactome in an unbiased manner, we generated mice that harbor a mouse prion
      protein promoter-driven cDNA encoding human APP-695 fused to a C-terminal
      affinity tag. Using this tag, we prepared mild detergent lysates from transgenic
      mouse brain cortical membrane preparations and isolated a number of previously
      identified APP-interacting proteins. In addition to these factors, mass
      spectrometric analysis revealed the presence of NEEP21 as a novel interacting
      protein. We now report that NEEP21 profoundly affects the processing of APP and
      Abeta production. Thus, this study demonstrates that using proteomic methods on
      our transgenic model can uncover important in vivo APP-interacting proteins that
      will provide insights into the biology of APP.

PMID- 21084624
TI  - Regeneration of new neurons is preserved in aged vomeronasal epithelia.
AB  - During normal and diseased aging, it is thought the capacity for tissue
      regeneration and repair in neuronal tissues diminishes. In the peripheral
      olfactory system, stem cell reservoirs permit regeneration of olfactory and
      vomeronasal sensory neurons, a unique capacity among neurons. Following injury, a
      large number of new neurons can be regenerated in a young animal. However, it is
      unknown whether this capacity for renewal exists in aged proliferative
      populations. Here, we report that neuronal replacement-associated proliferation
      continues in the vomeronasal organ of aged (18-24 months) mice. In addition, the
      potential for the aged stem cell to yield a mature neuron persisted at the same
      rate as that observed in young animals. Furthermore, the robust regenerative
      capacity to respond to both acute and sustained injury following olfactory
      bulbectomy remains intact even in very old animals. Hence, the neuronal
      epithelium lining the vomeronasal organ is unique in that it contains stem cells
      capable of generating functional neurons throughout life and in the aged animal
      in particular. This persistent regenerative capacity provides hope for neuronal
      replacement therapies in the aged nervous system.

PMID- 21084625
TI  - The caudal medial entorhinal cortex: a selective role in recollection-based
      recognition memory.
AB  - Recent studies have suggested that the caudal medial entorhinal cortex (cMEC) is
      specialized for path integration and spatial navigation. However, cMEC is part of
      a brain system that supports episodic memory for both spatial and nonspatial
      events, and so may play a role in memory function that goes beyond navigation.
      Here, we used receiver operating characteristic analysis to investigate the role
      of the cMEC in familiarity and recollection processes that underlie nonspatial
      recognition memory in rats. The results indicate that cMEC plays a critical and
      selective role in recollection-based performance, supporting the view that cMEC
      supports memory for the spatial and temporal context in which events occur.

PMID- 21084626
TI  - The somatosensory cortex of reeler mutant mice shows absent layering but intact
      formation and behavioral activation of columnar somatotopic maps.
AB  - Sensory information acquired via the large facial whiskers is processed and
      relayed in the whisker-to-barrel pathway, which shows multiple somatotopic maps
      of the receptor periphery. These maps consist of individual structural modules,
      the development of which may require intact cortical lamination. In the present
      study we examined the whisker-to-barrel pathway in the reeler mouse and thus used
      a model with disturbed cortical organization. A combination of histological
      (fluorescent Nissl and cytochrome oxidase staining) as well as molecular methods
      (c-Fos and laminar markers Rgs8, RORB, and ER81 expression) revealed wild type
      equivalent modules in reeler. At the neocortical level, however, we found
      extensive alterations in the layout of the individual modules of the map.
      Nevertheless, they showed a columnar organization that included compartments
      equivalent to those of their wild-type counterparts. Moreover, all examined
      modules showed distinct activation as a consequence of behavioral whisker
      stimulation. Analysis of the magnitude of the cortical lamination defect
      surprisingly revealed an extensive disorganization, rather than an inversion, as
      assumed previously. Striking developmental plasticity of thalamic innervation, as
      suggested by vGluT2 immunohistochemistry, seems to ensure the proper formation of
      columnar modules and topological maps even under highly disorganized conditions.

PMID- 21084627
TI  - Rhesus macaque theta-defensin isoforms: expression, antimicrobial activities, and
      demonstration of a prominent role in neutrophil granule microbicidal activities.
AB  - Mammalian defensins are cationic, antimicrobial peptides that play a central role
      in innate immunity. The peptides are composed of three structural subfamilies:
      alpha-, beta-, and theta-defensins. theta-defensins are macrocyclic
      octadecapeptides expressed only in Old World monkeys and orangutans and are
      produced by the pair-wise, head-to-tail splicing of nonapeptides derived from
      their respective precursors. The existence of three active theta-defensin genes
      predicts that six different RTDs (1-6) are produced in this species. In this
      study, we isolated and quantified RTDs 1-6 from the neutrophils of 10 rhesus
      monkeys. RTD-1 was the most abundant theta-defensin, constituting ~50% of the RTD
      content; total RTD content varied by as much as threefold between animals. All
      peptides tested were microbicidal at ~1 MUM concentrations. The contribution of
      theta-defensins to macaque neutrophil antimicrobial activity was assessed by
      analyzing the microbicidal properties of neutrophil granule extracts after
      neutralizing theta-defensin content with a specific antibody. theta-defensin
      neutralization markedly reduced microbicidal activities of the corresponding
      extracts. Macaque neutrophil granule extracts had significantly greater
      microbicidal activity than those of human neutrophils, which lack theta
      defensins. Supplementation of human granule extracts with RTD-1 markedly
      increased the microbicidal activity of these preparations, further demonstrating
      a prominent microbicidal role for theta-defensins.

PMID- 21084629
TI  - Macrophage motility requires distinct alpha5beta1/FAK and alpha4beta1/paxillin
      signaling events.
AB  - Macrophages function as key inflammatory mediators at sites of infection and
      tissue damage. Integrin and growth factor receptors facilitate recruitment of
      monocytes/macrophages to sites of inflammation in response to numerous
      extracellular stimuli. We have shown recently that FAK plays a role in regulating
      macrophage chemotaxis and invasion. As FAK is an established downstream mediator
      of integrin signaling, we sought to define the molecular circuitry involving FAK
      and the predominant beta1 integrin heterodimers expressed in these cells
      alpha4beta1 and alpha5beta1. We show that alpha4beta1 and alpha5beta1 integrins
      are required for efficient haptotactic and chemotactic invasion and that
      stimulation of these integrin receptors leads to the adoption of distinct
      morphologies associated with motility. FAK is required downstream of alpha5beta1
      for haptotaxis toward FN and chemotaxis toward M-CSF-1 and downstream of
      alpha4beta1 for the adoption of a polarized phenotype. The scaffolding molecule
      paxillin functions independently of FAK to promote chemotaxis downstream of
      alpha4beta1. These studies expand our understanding of beta1 integrin signaling
      networks that regulate motility and invasion in macrophages and thus, provide
      important new insights into mechanisms by which macrophages perform their diverse
      functions.

PMID- 21084628
TI  - The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN
      beta-mediated antiviral activity in vitro and in vivo.
AB  - The 2009 outbreak of pandemic H1N1 influenza, increased drug resistance, and the
      significant delay in obtaining adequate numbers of vaccine doses have heightened
      awareness of the need to develop new antiviral drugs that can be used
      prophylactically or therapeutically. Previously, we showed that the experimental
      anti-tumor drug DMXAA potently induced IFN-beta but relatively low TNF-alpha
      expression in vitro. This study confirms these findings in vivo and demonstrates
      further that DMXAA induces potent antiviral activity in vitro and in vivo. In
      vitro, DMXAA protected RAW 264.7 macrophage-like cells from VSV-induced
      cytotoxicity and moreover, inhibited replication of influenza, including the
      Tamiflu(r)-resistant H1N1 influenza A/Br strain, in MDCK cells. In vivo, DMXAA
      protected WT C57BL/6J but not IFN-beta(-/-) mice from lethality induced by the
      mouse-adapted H1N1 PR8 influenza strain when administered before or after
      infection. Protection was accompanied by mitigation of weight loss, increased IFN
      beta mRNA and protein levels in the lung, and significant inhibition of viral
      replication in vivo early after DMXAA treatment. Collectively, this study
      provides data to support the use of DMXAA as a novel antiviral agent.

PMID- 21084630
TI  - Relative integrated IR absorption in the atmospheric window is not the same as
      relative radiative efficiency.

PMID- 21084631
TI  - High-throughput sequencing reveals a simple model of nucleosome energetics.
AB  - We use genome-wide nucleosome maps to study sequence specificity of intrinsic
      histone-DNA interactions. In contrast with previous approaches, we employ an
      analogy between a classical one-dimensional fluid of finite-size particles in an
      arbitrary external potential and arrays of DNA-bound histone octamers. We derive
      an analytical solution to infer free energies of nucleosome formation directly
      from nucleosome occupancies measured in high-throughput experiments. The sequence
      specific part of free energies is then captured by fitting them to a sum of
      energies assigned to individual nucleotide motifs. We have developed hierarchical
      models of increasing complexity and spatial resolution, establishing that
      nucleosome occupancies can be explained by systematic differences in mono- and
      dinucleotide content between nucleosomal and linker DNA sequences, with periodic
      dinucleotide distributions and longer sequence motifs playing a minor role.
      Furthermore, similar sequence signatures are exhibited by control experiments in
      which nucleosome-free genomic DNA is either sonicated or digested with
      micrococcal nuclease, making it possible that current predictions based on high
      throughput nucleosome-positioning maps are biased by experimental artifacts.

PMID- 21084632
TI  - Superfamily-wide portrait of serine hydrolase inhibition achieved by library
      versus-library screening.
AB  - Serine hydrolases (SHs) are one of the largest and most diverse enzyme classes in
      mammals. They play fundamental roles in virtually all physiological processes and
      are targeted by drugs to treat diseases such as diabetes, obesity, and
      neurodegenerative disorders. Despite this, we lack biological understanding for
      most of the 110+ predicted mammalian metabolic SHs, in large part because of a
      dearth of assays to assess their biochemical activities and a lack of selective
      inhibitors to probe their function in living systems. We show here that the vast
      majority (> 80%) of mammalian metabolic SHs can be labeled in proteomes by a
      single, active site-directed fluorophosphonate probe. We exploit this universal
      activity-based assay in a library-versus-library format to screen 70+ SHs against
      140+ structurally diverse carbamates. Lead inhibitors were discovered for ~40% of
      the screened enzymes, including many poorly characterized SHs. Global profiles
      identified carbamate inhibitors that discriminate among highly sequence-related
      SHs and, conversely, enzymes that share inhibitor sensitivity profiles despite
      lacking sequence homology. These findings indicate that sequence relatedness is
      not a strong predictor of shared pharmacology within the SH superfamily. Finally,
      we show that lead carbamate inhibitors can be optimized into pharmacological
      probes that inactivate individual SHs with high specificity in vivo.

PMID- 21084633
TI  - Drug resistance against HCV NS3/4A inhibitors is defined by the balance of
      substrate recognition versus inhibitor binding.
AB  - Hepatitis C virus infects an estimated 180 million people worldwide, prompting
      enormous efforts to develop inhibitors targeting the essential NS3/4A protease.
      Resistance against the most promising protease inhibitors, telaprevir,
      boceprevir, and ITMN-191, has emerged in clinical trials. In this study, crystal
      structures of the NS3/4A protease domain reveal that viral substrates bind to the
      protease active site in a conserved manner defining a consensus volume, or
      substrate envelope. Mutations that confer the most severe resistance in the
      clinic occur where the inhibitors protrude from the substrate envelope, as these
      changes selectively weaken inhibitor binding without compromising the binding of
      substrates. These findings suggest a general model for predicting the
      susceptibility of protease inhibitors to resistance: drugs designed to fit within
      the substrate envelope will be less susceptible to resistance, as mutations
      affecting inhibitor binding would simultaneously interfere with the recognition
      of viral substrates.

PMID- 21084634
TI  - Role for a somatically diversified lectin in resistance of an invertebrate to
      parasite infection.
AB  - Invertebrates lack adaptive immune systems homologous to those of vertebrates,
      yet it is becoming increasingly clear that they can produce diversified antigen
      recognition molecules. We have previously noted that the snail Biomphalaria
      glabrata produces a secreted lectin, fibrinogen-related protein 3 (FREP3),
      unusual among invertebrate defense molecules because it is somatically
      diversified by gene conversion and point mutation. Here we implicate FREP3 in
      playing a central role in resistance to a major group of snail pathogens,
      digenetic trematodes. FREP3 is up-regulated in three models of resistance of B.
      glabrata to infection with Schistosoma mansoni or Echinostoma paraensei, and
      functions as an opsonin favoring phagocytosis by hemocytes. Knock-down of FREP3
      in resistant snails using siRNA-mediated interference resulted in increased
      susceptibility to E. paraensei, providing a direct link between a gastropod
      immune molecule and resistance to trematodes. FREP3 up-regulation is also
      associated with heightened responsiveness following priming with attenuated
      digenetic trematodes (acquired resistance) in this model invertebrate immune
      system.

PMID- 21084635
TI  - Quorum sensing and a global regulator TsrA control expression of type VI
      secretion and virulence in Vibrio cholerae.
AB  - Vibrio cholerae is a human pathogen that causes the life-threatening diarrheal
      disease cholera. A type VI secretion system (T6SS) was recently shown to be
      required for full virulence in the O37 serogroup strain V52, which causes only
      sporadic human disease, but T6SS is not expressed in seventh pandemic O1 El Tor
      strains under standard laboratory conditions. In this study, we show that in the
      O1 El Tor strain C6706, T6SS is repressed by both quorum sensing and the
      uncharacterized protein VC0070 (TsrA). Disruption of TsrA and the quorum sensing
      regulator LuxO induces expression and secretion of the T6SS substrate Hcp, and
      this is dependent on the downstream regulator HapR, which directly binds to the
      promoter region of the T6SS genes hcp1 and hcp2 to induce expression. The
      activated T6SS in C6706 is functional and can translocate the effector protein
      VgrG-1 into macrophage cells, and T6SS activation leads to fecal diarrhea and
      intestinal inflammation in infant rabbits. Using an infant mouse infection model,
      we show that deletion of tsrA results in a 9.3-fold increase in intestinal
      colonization compared with wild type. TsrA functions as a global regulator to
      activate expression of hemagglutinin protease and repress cholera toxin and toxin
      coregulated pilus. Our findings provide significant insight into the molecular
      mechanism of T6SS and ToxT regulon gene regulation by quorum sensing and TsrA.

PMID- 21084636
TI  - Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and
      function of glutamatergic synapses.
AB  - Growing evidence indicates that Wingless-type (Wnt) signaling plays an important
      role in the maturation of the central nervous system. We report here that
      Wingless-type family member 5A (Wnt-5a) is expressed early in development and
      stimulates dendrite spine morphogenesis, inducing de novo formation of spines and
      increasing the size of the preexisting ones in hippocampal neurons. Wnt-5a
      increased intracellular calcium concentration in dendritic processes and the
      amplitude of NMDA spontaneous miniature currents. Acute application of Wnt-5a
      increased the amplitude of field excitatory postsynaptic potentials (fEPSP) in
      hippocampal slices, an effect that was prevented by calcium-channel blockers. The
      physiological relevance of our findings is supported by studies showing that Wnt
      scavengers decreased spine density, miniature excitatory postsynaptic currents,
      and fEPSP amplitude. We conclude that Wnt-5a stimulates different aspects of
      synaptic differentiation and plasticity in the mammalian central nervous system.

PMID- 21084637
TI  - Sumoylation activates the transcriptional activity of Pax-6, an important
      transcription factor for eye and brain development.
AB  - Pax-6 is an evolutionarily conserved transcription factor regulating brain and
      eye development. Four Pax-6 isoforms have been reported previously. Although the
      longer Pax-6 isoforms (p46 and p48) bear two DNA-binding domains, the paired
      domain (PD) and the homeodomain (HD), the shorter Pax-6 isoform p32 contains only
      the HD for DNA binding. Although a third domain, the proline-, serine- and
      threonine-enriched activation (PST) domain, in the C termini of all Pax-6
      isoforms mediates their transcriptional modulation via phosphorylation, how p32
      Pax-6 could regulate target genes remains to be elucidated. In the present study,
      we show that sumoylation at K91 is required for p32 Pax-6 to bind to a HD
      specific site and regulate expression of target genes. First, in vitro
      synthesized p32 Pax-6 alone cannot bind the P3 sequence, which contains the HD
      recognition site, unless it is preincubated with nuclear extracts precleared by
      anti-Pax-6 but not by anti-small ubiquitin-related modifier 1 (anti-SUMO1)
      antibody. Second, in vitro-synthesized p32 Pax-6 can be sumoylated by SUMO1, and
      the sumoylated p32 Pax-6 then can bind to the P3 sequence. Third, Pax-6 and SUMO1
      are colocalized in the embryonic optic and lens vesicles and can be
      coimmunoprecipitated. Finally, SUMO1-conjugated p32 Pax-6 exists in both the
      nucleus and cytoplasm, and sumoylation significantly enhances the DNA-binding
      ability of p32 Pax-6 and positively regulates gene expression. Together, our
      results demonstrate that sumoylation activates p32 Pax-6 in both DNA-binding and
      transcriptional activities. In addition, our studies demonstrate that p32 and p46
      Pax-6 possess differential DNA-binding and regulatory activities.

PMID- 21084638
TI  - How T cells take developmental decisions by using the aryl hydrocarbon receptor
      to sense the environment.

PMID- 21084639
TI  - Are oncogenes sufficient to cause human cancer?

PMID- 21084640
TI  - Antagonist action of progesterone at sigma-receptors in the modulation of voltage
      gated sodium channels.
AB  - sigma-Receptors are integral membrane proteins that have been implicated in a
      number of biological functions, many of which involve the modulation of ion
      channels. A wide range of synthetic ligands activate sigma-receptors, but
      endogenous sigma-receptor ligands have proven elusive. One endogenous ligand,
      dimethyltryptamine (DMT), has been shown to act as a sigma-receptor agonist.
      Progesterone and other steroids bind sigma-receptors, but the functional
      consequences of these interactions are unclear. Here we investigated progesterone
      binding to sigma(1)- and sigma(2)-receptors and evaluated its effect on sigma
      receptor-mediated modulation of voltage-gated Na(+) channels. Progesterone binds
      both sigma-receptor subtypes in liver membranes with comparable affinities and
      blocks photolabeling of both subtypes in human embryonic kidney 293 cells that
      stably express the human cardiac Na(+) channel Na(v)1.5. Patch-clamp recording in
      this cell line tested Na(+) current modulation by the sigma-receptor ligands
      ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action
      of these ligands to varying degrees, and some of these actions were reduced by
      sigma(1)-receptor knockdown with small interfering RNA. Progesterone inhibition
      of channel modulation by drugs was consistent with stronger antagonism of
      sigma(2)-receptors. By contrast, progesterone inhibition of channel modulation by
      DMT was consistent with stronger antagonism of sigma(1)-receptors. Progesterone
      binding to sigma-receptors blocks sigma-receptor-mediated modulation of a voltage
      gated ion channel, and this novel membrane action of progesterone may be relevant
      to changes in brain and cardiovascular function during endocrine transitions.

PMID- 21084641
TI  - ILK mediates the effects of strain on intestinal epithelial wound closure.
AB  - The intestinal epithelium is subjected to repetitive deformation during normal
      gut function by peristalsis and villous motility. Such repetitive strain promotes
      intestinal epithelial migration across fibronectin in vitro, but signaling
      mediators for this are poorly understood. We hypothesized that integrin-linked
      kinase (ILK) mediates strain-stimulated migration in intestinal epithelial cells
      cultured on fibronectin. ILK kinase activity increased rapidly 5 min after strain
      induction in both Caco-2 and intestinal epithelial cell-6 (IEC-6) cells. Wound
      closure in response to strain was reduced in ILK small interfering RNA (siRNA)
      transfected Caco-2 cell monolayers when compared with control siRNA-transfected
      Caco-2 cells. Pharmacological blockade of phosphatidylinositol-3 kinase (PI3K) or
      Src or reducing Src by siRNA prevented strain activation of ILK. ILK
      coimmunoprecipitated with focal adhesion kinase (FAK), and this association was
      decreased by mutation of FAK Tyr925 but not FAK Tyr397. Strain induction of FAK
      Tyr925 phosphorylation but not FAK Tyr397 or FAK Tyr576 phosphorylation was
      blocked in ILK siRNA-transfected cells. ILK-Src association was stimulated by
      strain and was blocked by the Src inhibitor PP2. Finally, ILK reduction by siRNA
      inhibited strain-induced phosphorylation of myosin light chain and Akt. These
      results suggest a strain-dependent signaling pathway in which ILK association
      with FAK and Src mediates the subsequent downstream strain-induced motogenic
      response and suggest that ILK induction by repetitive deformation may contribute
      to recovery from mucosal injury and restoration of the mucosal barrier in
      patients with prolonged ileus. ILK may therefore be an important target for
      intervention to maintain the mucosa in such patients.

PMID- 21084643
TI  - American Journal of Physiology-Cell Physiology theme: hypoxia.

PMID- 21084642
TI  - Intracellular signaling pathways regulating net protein balance following
      diaphragm muscle denervation.
AB  - Unilateral denervation (DNV) of rat diaphragm muscle increases protein synthesis
      at 3 days after DNV (DNV-3D) and degradation at DNV-5D, such that net protein
      breakdown is evident by DNV-5D. On the basis of existing models of protein
      balance, we examined DNV-induced changes in Akt, AMP-activated protein kinase
      (AMPK), and ERK&frac12; activation, which can lead to increased protein synthesis
      via mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K), glycogen synthase
      kinase-3beta (GSK3beta), or eukaryotic initiation factor 4E (eIF4E), and
      increased protein degradation via forkhead box protein O (FoxO). Protein
      phosphorylation was measured using Western analyses through DNV-5D. Akt
      phosphorylation decreased at 1 h and 6 h after DNV compared with sham despite
      decreased AMPK phosphorylation. Both Akt and AMPK phosphorylation returned to
      sham levels by DNV-1D. Phosphorylation of their downstream effector mTOR
      (Ser2481) did not change at any time point after DNV, and phosphorylated p70S6K
      and eIF4E-binding protein 1 (4EBP1) increased only by DNV-5D. In contrast,
      ERK&frac12; phosphorylation and its downstream effector eIF4E increased 1.7-fold
      at DNV-1D and phosphorylated GSK3beta increased 1.5-fold at DNV-3D (P < 0.05 for
      both comparisons). Thus, following DNV there are differential effects on protein
      synthetic pathways with preferential activation of GSK3beta and eIF4E over
      p70S6K. FoxO1 nuclear translocation occurred by DNV-1D, consistent with its role
      in increasing expression of atrogenes necessary for subsequent ubiquitin
      proteasome activation evident by DNV-5D. On the basis of our results, increased
      protein synthesis following DNV is associated with changes in ERK&frac12;
      dependent pathways, but protein degradation results from downregulation of Akt
      and nuclear translocation of FoxO1. No single trigger is responsible for protein
      balance following DNV. Protein balance in skeletal muscle depends on multiple
      synthetic/degradation pathways that should be studied in concert.

PMID- 21084644
TI  - Transmural differences in respiratory capacity across the rat left ventricle in
      health, aging, and streptozotocin-induced diabetes mellitus: evidence that
      mitochondrial dysfunction begins in the subepicardium.
AB  - In diabetic cardiomyopathy, ventricular dysfunction occurs in the absence of
      hypertension or atherosclerosis and is accompanied by altered myocardial
      substrate utilization and depressed mitochondrial respiration. It is not known if
      mitochondrial function differs across the left ventricular (LV) wall in diabetes.
      In the healthy heart, the inner subendocardial region demonstrates higher rates
      of blood flow, oxygen consumption, and ATP turnover compared with the outer
      subepicardial region, but published transmural respirometric measurements have
      not demonstrated differences. We aim to measure mitochondrial function in Wistar
      rat LV to determine the effects of age, streptozotocin-diabetes, and LV layer.
      High-resolution respirometry measured indexes of respiration in saponin-skinned
      fibers dissected from the LV subendocardium and subepicardium of 3-mo-old rats
      after 1 mo of streptozotocin-induced diabetes and 4-mo-old rats following 2 mo of
      diabetes. Heart rate and heartbeat duration were measured under isoflurane
      anesthesia using a fetal-Doppler, and transmission electron microscopy was
      employed to observe ultrastructural differences. Heart rate decreased with age
      and diabetes, whereas heartbeat duration increased with diabetes. While there
      were no transmural respirational differences in young healthy rat hearts, both
      myocardial layers showed a respiratory depression with age (30-40%). In 1-mo
      diabetic rat hearts only subepicardial respiration was depressed, whereas after 2
      mo diabetes, respiration in subendocardial and subepicardial layers was depressed
      and showed elevated leak (state 2) respiration. These data provide evidence that
      mitochondrial dysfunction is first detectable in the subepicardium of diabetic
      rat LV, whereas there are measureable changes in LV mitochondria after only 4 mo
      of aging.

PMID- 21084645
TI  - Contributions of enriched cereal-grain products, ready-to-eat cereals, and
      supplements to folic acid and vitamin B-12 usual intake and folate and vitamin B
      12 status in US children: National Health and Nutrition Examination Survey
      (NHANES), 2003-2006.
AB  - BACKGROUND: US children consume folic acid from multiple sources. These sources
      may contribute differently to usual intakes above the age-specific tolerable
      upper intake level (UL) for folic acid and to folate and vitamin B-12 status.
      OBJECTIVE: We estimated usual daily folic acid intakes above the UL and adjusted
      serum and red blood cell folate, serum vitamin B-12, homocysteine, and
      methylmalonic acid (MMA) concentrations in US children by age group and by the
      following 3 major folic acid intake sources: enriched cereal-grain products
      (ECGP), ready-to-eat cereals (RTE), and supplements containing folic acid (SUP).
      DESIGN: We analyzed data in 4 groups of children aged 1-3, 4-8, 9-13, and 14-18 y
      from the National Health and Nutrition Examination Survey (NHANES), 2003-2006 (n
      = 7161). RESULTS: A total of 19-48% of children consumed folic acid from ECGP
      only. Intakes above the UL varied from 0-0.1% of children who consumed ECGP only
      to 15-78% of children who consumed ECGP+RTE+SUP. In children aged 1-8 y, 99-100%
      of those who consumed >= 200 MUg folic acid/d from supplements exceeded their UL.
      Although < 0.5% of children had folate deficiency or low vitamin B-12 status, the
      consumption of RTE or SUP with folic acid was associated with higher mean folate
      and vitamin B-12 concentrations and, in some older children, with lower
      homocysteine and MMA concentrations. CONCLUSIONS: Our data suggest that the
      majority of US children consume more than one source of folic acid.
      Postfortification, the consumption of RTE or SUP increases usual daily intakes
      and blood concentrations of folate and vitamin B-12.

PMID- 21084646
TI  - Recalculation of the calcium requirement of adult men.
AB  - BACKGROUND: There is uncertainty about the calcium requirement with particular
      respect to age and sex differences and the calculation of skin calcium losses.
      OBJECTIVE: We calculated the calcium requirement of adult men from a homogenous
      set of calcium balances and a robust estimate of calcium loss through the skin.
      DESIGN: We reviewed available high-quality published calcium balances in men and
      retrieved 219 balances; we noted a fall in calcium absorption in individuals >60
      y of age. Our analysis was confined to 157 men <=59 y of age with intakes of
      <=1100 mg Ca. RESULTS: The mean age of the men was 38 y (range: 17-59 y), and the
      mean duration of the balances was 107 d (9-480 d). We assumed skin calcium losses
      of 40 mg Ca/d on the basis of the calcium content of insensible water loss. There
      was a highly significant correlation between calcium intake and the net absorbed
      calcium (R(2) = 0.59), but inspection and physiologic considerations led us to
      use the logarithmic transformation of intake, which yielded the equation Ca
      absorbed = 210 log Ca intake - 1135 mg Ca. The calcium intake at which urine
      calcium plus skin calcium losses were equal to the net absorbed calcium was
      rounded to 750 mg Ca as the requirement, which implied a recommended allowance of
      900 mg Ca. CONCLUSION: We conclude that the mean calcium requirement of adult men
      <60 y of age is 750 mg Ca/d, and the Recommended Dietary Allowance should be 900
      mg Ca.

PMID- 21084647
TI  - A high-sodium diet is associated with acute decompensated heart failure in
      ambulatory heart failure patients: a prospective follow-up study.
AB  - BACKGROUND: A low-sodium diet is an accepted treatment of patients with heart
      failure (HF), although minimal evidence exists on the appropriate amount of
      sodium intake for this population. Certain HF guidelines have liberalized dietary
      sodium recommendations, which actually exceed guidelines for healthy adults.
      OBJECTIVES: We tested the hypothesis that high sodium intake is related to acute
      decompensated HF (ADHF) in ambulatory HF patients. Secondary outcomes included
      all-cause hospitalization and mortality. DESIGN: We prospectively enrolled
      medically stable, ambulatory patients with systolic HF (n = 123; mean +/- SD age:
      60 +/- 13 y) from 2 outpatient HF clinics from 2003 to 2007. Baseline estimates
      of dietary sodium and other nutrient intakes were obtained from two 3-d food
      records. RESULTS: The median follow-up time was 3.0 y. Mean (+/-SD) sodium
      intakes were 1.4 +/- 0.3, 2.4 +/- 0.3, and 3.8 +/- 0.8 g Na/d in the lower,
      middle, and upper tertiles, respectively. Cumulative ADHF event rates at 3 y were
      12 +/- 6%, 15 +/- 7%, and 46 +/- 11% in the low, middle, and upper tertiles,
      respectively (log-rank P = 0.001). For ADHF, the upper tertile was associated
      with an adjusted hazard ratio of 2.55 (95% CI: 1.61, 4.04; P < 0.001). Time-to
      event probabilities were significant for mortality (log-rank P = 0.022) but not
      for all-cause hospitalization (log-rank P = 0.224). The high-sodium tertile was
      associated with an adjusted hazard ratio of 1.39 (95% CI: 1.06, 1.83; P = 0.018)
      for all-cause hospitalization and 3.54 (95% CI: 1.46, 8.62; P = 0.005) for
      mortality. CONCLUSIONS: To our knowledge, this study provides the first
      prospective evidence that ambulatory HF patients who consume higher amounts of
      sodium are at greater risk of an ADHF event. These data provide support for more
      stringent sodium intake guidelines than those currently recommended for HF
      patients.

PMID- 21084648
TI  - Randomized controlled trial on weight loss in obstructive sleep apnea:
      inappropriate analysis limits main conclusion.

PMID- 21084649
TI  - Exercising before protein intake allows for greater use of dietary protein
      derived amino acids for de novo muscle protein synthesis in both young and
      elderly men.
AB  - BACKGROUND: Sarcopenia seems to be attributed to a blunted muscle protein
      synthetic response to food intake and exercise. This blunted response could be
      the result of impaired protein digestion and absorption kinetics and lead to
      lower postprandial plasma amino acid availability. OBJECTIVE: The objective was
      to compare in vivo dietary protein digestion and absorption kinetics and
      subsequent postprandial muscle protein synthesis rates at rest and after exercise
      between young and elderly men. DESIGN: Young and elderly men consumed a 20-g
      bolus of intrinsically L-[1-(13)C]phenylalanine-labeled protein at rest or after
      exercise. Continuous infusions with L-[ring-(2)H(5)]phenylalanine were applied,
      and blood and muscle samples were collected to assess in vivo protein digestion
      and absorption kinetics and subsequent postprandial muscle protein synthesis
      rates. RESULTS: Exogenous phenylalanine appearance rates expressed over time did
      not differ between groups. No differences were observed in plasma phenylalanine
      availability between the young (51 +/- 2%) and elderly (51 +/- 1%) men or between
      the rest (52 +/- 1%) and exercise (49 +/- 1%) conditions. Muscle protein
      synthesis rates calculated from the oral tracer were 0.0620 +/- 0.0065%/h and
      0.0560 +/- 0.0039%/h for the rest condition and 0.0719 +/- 0.0057%/h and 0.0727
      +/- 0.0040%/h for the exercise condition in young and elderly men, respectively
      (age effect: P = 0.62; exercise effect: P < 0.05; interaction of age and
      exercise: P = 0.52). CONCLUSIONS: Dietary protein digestion and absorption
      kinetics are not impaired after exercise or at an older age. Exercising before
      protein intake allows for a greater use of dietary protein-derived amino acids
      for de novo muscle protein synthesis in both young and elderly men. This trial
      was registered at clinicaltrials.gov as NCT00557388.

PMID- 21084650
TI  - Effects of eating breakfast compared with skipping breakfast on ratings of
      appetite and intake at subsequent meals in 8- to 10-y-old children.
AB  - BACKGROUND: Cross-sectional data indicate an inverse relation between breakfast
      consumption and child weight. It has been suggested that skipping breakfast may
      adversely affect appetite in children, which could lead to overeating later in
      the day. OBJECTIVE: The aim of this study was to test the effects of consuming
      breakfast compared with omitting breakfast on appetite ratings and energy intake
      at subsequent meals in 8- to 10-y-old children. DESIGN: Twenty-one children
      participated in 2 test visits during which they were served either a compulsory
      breakfast or no breakfast. On both visits, subjects were also served lunch, which
      was consumed ad libitum. Subjects rated their appetite throughout the morning;
      parents completed food records that captured children's intake for the remainder
      of the day. RESULTS: There was no significant main effect of breakfast condition
      on energy intake at lunch (P = 0.36) or throughout the remainder of the day (P =
      0.85). There was a significant main effect of breakfast condition (P = 0.04) on
      total daily energy intake, which indicated that on the day when the subjects did
      not eat breakfast, they consumed 362 fewer calories over the course of the day
      than when they did eat breakfast. On the day when no breakfast was served,
      subjects indicated that they were significantly hungrier, less full, and could
      consume more food before lunch than on the day when they did eat breakfast (P <
      0.001). CONCLUSIONS: Omitting breakfast affected children's appetite ratings but
      not their energy intake at subsequent meals. The dissonance between children's
      subjective ratings of prospective consumption and their actual intake should be
      further examined.

PMID- 21084651
TI  - Adipose tissue palmitoleic acid and obesity in humans: does it behave as a
      lipokine?
AB  - BACKGROUND: Animal models have shown that adipose-derived palmitoleic acid may
      serve as a lipokine that contributes to resistance to diet-induced obesity.
      Studies in humans have evaluated only plasma palmitoleic acid concentrations,
      which reflect stearoyl-coenzyme A desaturase 1 (SCD1) activity in the liver and
      are associated with increased risk of obesity. These apparent opposite effects of
      palmitoleic acid deserve further research in humans. Because carbohydrate intake
      can increase hepatic SCD1 activity, it could be used as a stratifying variable to
      disentangle the effects of adipose tissue SCD1 compared with the effects of liver
      SCD1 activity on obesity. OBJECTIVE: We examined whether the effects of adipose
      tissue palmitoleic acid and SCD1 activity were associated with decreased obesity
      prevalence and whether this association was modified by carbohydrate intake.
      DESIGN: Prevalence ratios (PRs) of obesity [body mass index (in kg/m2) > 30] were
      examined in a cross-sectional study in 1926 adults in Costa Rica. Two
      desaturation indexes (16:1/16:0 and 18:1/18:0) were used as surrogate measures of
      adipose tissue SCD1 activity. RESULTS: We observed a positive association between
      adipose tissue palmitoleic acid concentrations and obesity (PR for lowest
      compared with highest quintiles of palmitoleic acid: 2.27; 95% CI: 1.52, 3.38; P
      for trend < 0.0001). A significant association was also observed between obesity
      and adipose desaturation indexes. The association between adipose tissue
      palmitoleic acid concentrations and obesity was attenuated in persons with low
      carbohydrate intake. CONCLUSIONS: There is no direct evidence that adipose tissue
      palmitoleic acid behaves as a lipokine to reduce obesity occurrence in humans.
      However, the attenuation of the association by low carbohydrate intake warrants
      further research on adipose-derived palmitoleic acid and obesity risk.

PMID- 21084652
TI  - Arginine flux, but not nitric oxide synthesis, decreases in adolescent girls
      compared with adult women during pregnancy.
AB  - NO has been proposed as a mediator of vascular expansion during pregnancy.
      Inability to increase NO synthesis and/or production of its precursor, arginine,
      may contribute to pregnancy-induced hypertension. Adolescents have a higher
      incidence of gestational hypertension. It is not known whether pregnant
      adolescents can produce sufficient arginine to meet overall demands. Our
      objective was to measure and compare the arginine flux and NO synthesis rates of
      pregnant adolescents and adult women. Arginine, citrulline, and NO kinetics were
      measured by i.v. infusions of (15)N(2)-argininine and (2)H(2)-citrulline in 8
      adolescents and 8 adult women in the fasted state at the end of the first and the
      beginning of the 3rd trimesters of pregnancy. Arginine flux decreased (P < 0.05)
      from trimester 1 to 3 in the adolescents but not in the adult women. NO synthesis
      rate did not change significantly in either group from trimester 1 to 3. In
      trimester 3, there was a positive association (r = 0.55; P = 0.02) between
      arginine flux and participants' age, indicating that flux was slower in the
      younger participants. These findings suggest that after a brief period of food
      deprivation, the pregnant adolescent cannot maintain arginine production like her
      adult counterpart in late pregnancy. This inability to maintain arginine
      production seems to be related to her younger age. It does not, however, affect
      her ability to synthesize NO in late pregnancy.

PMID- 21084653
TI  - Enhanced expression and glucocorticoid-inducibility of hepatic cytochrome P450 3A
      involve recruitment of the pregnane-X-receptor to promoter elements in rats fed
      soy protein isolate.
AB  - Previous studies and Expt. 1 of the current study demonstrate that diets made
      with soy protein isolate (SPI) enhance the glucocorticoid-inducibility of hepatic
      cytochrome P450 (CYP)3A-dependent monooxygenase activities (P < 0.05) compared
      with diets made with casein (CAS). To determine the underlying molecular
      mechanism, in a second experiment, we analyzed the time course of dexamethasone
      (DEX)-induction of hepatic CYP3A mRNA expression on postnatal d (PND) 25 and
      PND60 in male and female rats fed SPI- or CAS-based diets. After 50 mg(/)kg DEX,
      CYP3A1 mRNA expression increased >200-fold in SPI-fed males and females at PND25
      compared with a 100-fold increase in CAS-fed rats (P < 0.05). The DEX-induced
      increase in CYP3A1 mRNA in SPI-fed rats on PND60 was also greater than that in
      CAS-fed rats. The induction by DEX of CYP3A2 mRNA was 1- to 3-fold greater in
      rats fed SPI compared with those fed CAS on PND25 (P < 0.05). Quantitation of
      newly synthesized CYP3A1 RNA transcripts by nuclear run-on analysis demonstrated
      a greater rate of basal transcription in SPI-fed compared with CAS-fed rats on
      PND60 accompanied by greater binding of the pregnane X receptor (PXR) to a
      response element on the CYP3A1 promoter in SPI-fed compared with CAS-fed rats (P
      < 0.05). These data suggest that increased hepatic CYP3A expression and
      inducibility following SPI feeding involves recruitment of PXR to its response
      element and suggests that soy consumption has potential effects on metabolism and
      transport of a wide variety of drugs and on bile acid homeostasis via proteins
      regulated by this transcription factor.

PMID- 21084654
TI  - Metabolomic analysis of plasma metabolites that may mediate effects of rye bread
      on satiety and weight maintenance in postmenopausal women.
AB  - The evidence of the beneficial health effects of dietary fiber and whole grain
      consumption is strong, but the underlying mechanisms are not completely
      understood. Here, we investigate how the consumption of high-fiber rye bread (RB)
      or white-wheat bread (WB) modifies the plasma metabolomic profiles in
      postmenopausal women. The study was a randomized crossover trial consisting of 8
      wk intervention periods and an 8-wk washout period. The study included 39
      postmenopausal women with elevated serum total cholesterol (5.0-8.5 mmol/L) and
      BMI 20-33 kg/m(2). During the intervention periods, the study breads contributed
      to least 20% of total energy intake. Two analytical platforms for metabolomics
      were applied. Lipidomic analysis was performed using ultra performance liquid
      chromatography coupled to electrospray ionization MS and the other metabolites,
      including sterols, organic acids, and alcohols, were analyzed by 2-dimensional GC
      coupled to time-of-flight MS. Altogether, 540 metabolites were profiled. Ribitol
      (P < 0.001), ribonic acid (P < 0.001), and indoleacetic acid (P < 0.001)
      increased during the RB consumption period. Ribonic acid correlated positively
      with tryptophan (r = 0.40; P = 0.003), which is a precursor for the biosynthesis
      of hunger-depressing serotonin. There were no changes in plasma lipidomic
      profiles during the RB or WB intervention periods. The results suggest that 8-wk
      consumption of high-fiber rye bread increases metabolites that might mediate
      positive effects of rye bread on satiety and weight maintenance.

PMID- 21084655
TI  - Serum 25-hydroxyvitamin D is a predictor of serum 1,25-dihydroxyvitamin D in
      overweight and obese patients.
AB  - Recent research suggests that 1,25-dihydroxyvitamin D [1,25(OH)(2)D], a steroid
      hormone that regulates calcium homeostasis, may also play a role in the
      development and progression of cancer, multiple sclerosis, cardiovascular, and
      other diseases. Decreased serum 1,25(OH)(2)D concentrations are often observed in
      overweight and obese patients. However, little is known about the factors that
      may influence 1,25(OH)(2)D renal synthesis, because it is generally accepted that
      serum 1,25(OH)(2)D concentration is strictly regulated by parathyroid hormone and
      serum concentrations of calcium and phosphorus. In this study, the associations
      among serum 1,25(OH)(2)D, serum 25-hydroxyvitamin D [25(OH)D], and body
      composition were analyzed in 1779 patients with excess body weight registered in
      a Metabolic and Medical Lifestyle Management Clinic in Oslo, Norway. According to
      our results, serum 25(OH)D, adiposity, age, season of blood sampling, and gender
      directly influence serum 1,25(OH)(2)D (r = 0.33; P < 0.001), with serum 25(OH)D
      being the strongest predictor for serum 1,25(OH)(2)D. The 1,25(OH)(2)D
      concentrations were 25.4 pmol/L (95% Cl: 19.3-31.5; P < 0.001) lower in the
      lowest 25(OH)D quartile to compared with highest quartile. A seasonal variation
      was observed for both vitamin D metabolites. Thus, our results suggest that in
      patients with excess body weight, serum 1,25(OH)(2)D concentrations were
      associated with 25(OH)D and varied during the year. Therefore, it may also be
      valuable to measure both serum 25(OH)D and 1,25(OH)(2)D for the evaluation of
      vitamin D status in overweight and obese persons.

PMID- 21084656
TI  - Intestinal glucose absorption but not endogenous glucose production differs
      between colostrum- and formula-fed neonatal calves.
AB  - Glucose supply markedly changes during the transition to extrauterine life. In
      this study, we investigated diet effects on glucose metabolism in neonatal
      calves. Calves were fed colostrum (C; n = 7) or milk-based formula (F; n = 7)
      with similar nutrient content up to d 4 of life. Blood plasma samples were taken
      daily before feeding and 2 h after feeding on d 4 to measure glucose, lactate,
      nonesterified fatty acids, protein, urea, insulin, glucagon, and cortisol
      concentrations. On d 2, additional blood samples were taken to measure glucose
      first-pass uptake (FPU) and turnover by oral [U-(13)C]-glucose and i.v. [6,6
      (2)H(2)]-glucose infusion. On d 3, endogenous glucose production and
      gluconeogenesis were determined by i.v. [U-(13)C]-glucose and oral deuterated
      water administration after overnight feed deprivation. Liver tissue was obtained
      2 h after feeding on d 4 and glycogen concentration and activities and mRNA
      abundance of gluconeogenic enzymes were measured. Plasma glucose and protein
      concentrations and hepatic glycogen concentration were higher (P < 0.05), whereas
      plasma urea, glucagon, and cortisol (d 2) concentrations as well as hepatic
      pyruvate carboxylase mRNA level and activity were lower (P < 0.05) in group C
      than in group F. Orally administered [U-(13)C]-glucose in blood was higher (P <
      0.05) but FPU tended to be lower (P < 0.1) in group C than in group F. The
      improved glucose status in group C resulted from enhanced oral glucose
      absorption. Metabolic and endocrine changes pointed to elevated amino acid
      degradation in group F, presumably to provide substrates to meet energy
      requirements and to compensate for impaired oral glucose uptake.

PMID- 21084657
TI  - The majority of patients with Achilles tendinopathy recover fully when treated
      with exercise alone: a 5-year follow-up.
AB  - BACKGROUND: Systematic reviews indicate that exercise has the most evidence of
      effectiveness in treatment of midportion Achilles tendinopathy. However, there is
      a lack of long-term follow-ups (>4 years). PURPOSE: To evaluate the 5-year
      outcome of patients treated with exercise alone and to examine if certain
      characteristics, such as level of kinesiophobia, age, and sex, were related to
      the effectiveness of the treatment. STUDY DESIGN: Case series; Level of evidence,
      4. METHODS: Thirty-four patients (47% women), 51 +/- 8.2 years old, were
      evaluated 5 years after initiation of treatment. The evaluation consisted of a
      questionnaire regarding recovery of symptoms and other treatments, the Victorian
      Institute of Sports Assessment-Achilles questionnaire (VISA-A) for symptoms, the
      Tampa Scale for Kinesiophobia, and tests of lower leg function. RESULTS: Twenty
      seven patients (80%) fully recovered from the initial injury; of these, 22 (65%)
      had no symptoms, and 5 (15%) had a new occurrence of symptoms. Seven patients
      (20%) had continued symptoms. Only 2 patients received another treatment
      (acupuncture and further exercise instruction). When compared with the other
      groups, the continued-symptoms group had lower VISA-A scores (P = .008 to .021)
      at the 5-year follow-up and the previous 1-year follow-up but not at any earlier
      evaluations. There were no significant differences among the groups in regard to
      sex, age, or physical activity level before injury. There was a significant (P =
      .005) negative correlation (-0.590) between the level of kinesiophobia and heel
      rise work recovery. CONCLUSION: The majority of patients with Achilles
      tendinopathy in this study fully recovered in regard to both symptoms and
      function when treated with exercise alone. Increased fear of movement might have
      a negative effect on the effectiveness of exercise treatment; therefore, a pain
      monitoring model should be used when patients are treated with exercise.

PMID- 21084658
TI  - Long-term stress distribution patterns across the elbow joint in baseball players
      assessed by computed tomography osteoabsorptiometry.
AB  - BACKGROUND: The distribution pattern of subchondral bone density is considered to
      highly reflect the stress distribution across a joint under long-term physiologic
      loading conditions. Therefore, the biomechanical characteristics over the elbow
      joint surface under long-term loading conditions of baseball pitching can be
      determined by a measurement of the distribution pattern. HYPOTHESIS: Stress
      distribution over the elbow joint surface alters with long-term pitching
      activities. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS:
      Computed tomography (CT) imaging data from the dominant elbow of 10 nonthrowing
      athletes, 10 college baseball fielders, and 10 college baseball pitchers were
      collected for the current analysis. The distribution of subchondral bone density
      through the distal articular surface of the humerus was measured using a CT
      osteoabsorptiometry method. The quantitative analysis of the obtained data
      focused on location and size of the maximum density area at the articular
      surface. RESULTS: The maximum density area of subchondral bone across the
      articular surface of the distal humerus was located in the posterior part of the
      trochlea in all subjects. This maximum density area was significantly increased
      in the pitcher group, compared with that in other groups. Additionally, the
      pitcher group demonstrated a significant distribution of the maximum density area
      in the anterior part of the capitellum. CONCLUSION: The results indicate that
      actual stress across the elbow is concentrated in the posterior part of the
      trochlea in humans. Baseball pitching may produce excessive or repetitive stress
      against not only this part, but also the anterior part of the capitellum. The
      majority of osteochondritis dissecans lesions affecting the elbow are found in
      the anterior part of the capitellum in throwing athletes. The results may support
      an important role of mechanical conditions in the cause of elbow osteochondritis
      dissecans.

PMID- 21084659
TI  - Effect of shoulder stabilization on career length in national football league
      athletes.
AB  - BACKGROUND: Shoulder instability and surgical stabilization are common in college
      football athletes. The effect of shoulder stabilization during college on the
      length of an athlete's career in the National Football League (NFL) has not been
      well examined. HYPOTHESIS: Athletes with a history of shoulder stabilization
      before the NFL combine have a shorter career than do matched controls. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: A database containing the
      injury history and career NFL statistics of athletes from 1987 to 2000 was used
      to match athletes with a history of shoulder stabilization and no other surgery
      or significant injury to controls without a history of any previous surgery or
      significant injury. Athletes were matched by position, year drafted, round
      drafted, and additional minor injury history. RESULTS: Forty-two athletes with a
      history of shoulder stabilization were identified and matched with controls. A
      history of shoulder stabilization significantly reduced the length of career in
      terms of years (5.2 +/- 3.9 vs 6.9 +/- 3.6 years; P = .01) and games played (56
      +/- 53 vs 77 +/- 50, P = .03) as compared with controls. By position, linemen and
      linebackers (20 athletes) with a history of shoulder stabilization had a
      significantly shorter career in years (4.7 +/- 3.8 vs 6.7 +/- 3.4 years; P =
      .049) and games played (51 +/- 58 vs 81 +/- 48; P = .046) than did controls.
      Among the other positions (22 athletes), the difference was not statistically
      significant in this small cohort. CONCLUSION: A history of shoulder stabilization
      shortens the expected career of a professional football player, particularly for
      linemen and linebackers. Further research is warranted to better understand how
      these injuries and surgeries affect an athlete's career and what can be done to
      improve the long-term outcome after treatment.

PMID- 21084661
TI  - Acquisition of humoral transplantation tolerance upon de novo emergence of B
      lymphocytes.
AB  - A major obstacle to transplantation tolerance is humoral immunity. In this paper,
      we demonstrate that the intrinsic developmental propensity of the B lymphocyte
      compartment for acquisition of self-tolerance can be harnessed to induce humoral
      unresponsiveness to transplanted alloantigens. In the current study, when
      transitional B cells developed in the presence of donor lymphoid cells, the
      mature B lymphocyte compartment failed to mount a donor-specific alloantibody
      response to an organ transplant--despite unrestrained acute T cell-mediated
      allograft rejection. Specifically, we generated an experimental system wherein a
      B6 strain B cell compartment developed de novo in the presence of F1 (B6xBALB/c)
      lymphoid cells and in a T cell-deficient setting. Following establishment of a
      steady-state B cell compartment, these B6 mice were transplanted with heterotopic
      cardiac allografts from allogeneic BALB/c donors. The mice were then inoculated
      with purified syngeneic B6 T cells. As expected, all cardiac allografts were
      acutely rejected. However, the B lymphocyte compartment of these mice was
      completely inert in its capacity to form a BALB/c-specific alloantibody response.
      Using an alloantigen-specific Ig transgenic system, we demonstrated that this
      profound degree of humoral tolerance was caused by clonal deletion of
      alloreactive specificities from the primary B cell repertoire. Thus, de novo B
      cell compartment development at the time of transplantation is of critical
      importance in recipient repertoire "remodeling" to a humoral tolerant state.

PMID- 21084660
TI  - The prognosis and predictors of sports function and activity at minimum 6 years
      after anterior cruciate ligament reconstruction: a population cohort study.
AB  - BACKGROUND: The predictors of anterior cruciate ligament reconstruction (ACLR)
      outcome at 6 years as measured by validated patient-based outcome instruments are
      unknown. HYPOTHESIS: Certain variables evaluated at the time of ACLR will predict
      return to sports function (as measured by the International Knee Documentation
      Committee [IKDC] questionnaire and the Knee injury and Osteoarthritis Outcome
      Score [KOOS] Sports and Recreation subscale), knee-related quality of life (KOOS
      Knee Related Quality of Life subscale), and activity level (Marx Activity Scale).
      Potential predictor variables include demographic factors, surgical technique and
      graft choice for ACLR, and intra-articular injuries and treatment. STUDY DESIGN:
      Cohort study; Level of evidence, 2. METHODS: All patients with unilateral ACLRs
      from 2002 currently enrolled in the MOON (Multicenter Orthopaedic Outcomes
      Network) cohort were evaluated. Patients completed the validated outcome
      instruments preoperatively. Physicians documented intra-articular pathologic
      abnormalities, treatment, and surgical techniques used at the time of surgery. At
      2 and 6 years postoperatively, patients completed the same validated outcome
      instruments. RESULTS: Follow-up was obtained at 2 years (88%) and at 6 years
      (84%). The cohort was 57% male with a median age of 23 years at enrollment. The
      ability to perform sports function was maintained at 6 years, but the Marx
      activity level continued to decline from baseline. Revision ACLR and use of
      allograft predicted worse outcomes on the IKDC and both KOOS subscales. Lateral
      meniscus treatment, smoking status, and body mass index at baseline were each
      predictors on 2 of 3 scales. The predictors of lower activity level were revision
      ACLR and female sex. CONCLUSION: Six years after ACLR, patients could perform
      sports-related functions and maintain a high knee-related quality of life similar
      to their 2-year level, although their physical activity level (Marx) dropped over
      time. Choosing autograft rather than allograft, not smoking, and having normal
      body mass index are advised to improve long-term outcomes.

PMID- 21084662
TI  - Myelin-reactive, TGF-beta-induced regulatory T cells can be programmed to develop
      Th1-like effector function but remain less proinflammatory than myelin-reactive
      Th1 effectors and can suppress pathogenic T cell clonal expansion in vivo.
AB  - Interest in the use of regulatory T cells (Tregs) as cellular therapeutics has
      been tempered by reports of naturally occurring Tregs losing Foxp3 expression and
      producing IL-17, raising concerns over a switch to pathogenic function under
      inflammatory conditions in vivo. TGF-beta-induced Tregs (inducible Tregs
      [iTregs]), generated in large numbers in response to disease-relevant Ags,
      represent the most amenable source of therapeutic Tregs. Using Foxp3-reporter T
      cells recognizing myelin basic protein (MBP), we investigated the capacity of
      iTregs to produce effector-associated cytokines under proinflammatory cytokine
      conditions in vitro and whether this translated into proinflammatory function in
      vivo. In contrast with naturally occurring Tregs, iTregs resisted conversion to
      an IL-17-producing phenotype but were able to express T-bet and to produce IFN
      gamma. iTregs initiated their T-bet expression during their in vitro induction,
      and this was dependent on exposure to IFN-gamma. IL-12 reignited iTreg expression
      of T-bet and further promoted iTreg production of IFN-gamma upon secondary
      stimulation. Despite losing Foxp3 expression and expressing both T-bet and IFN
      gamma, MBP-responsive IL-12-conditioned iTregs induced only mild CNS inflammation
      and only when given in high numbers. Furthermore, iTregs retained an ability to
      suppress naive T cell clonal expansion in vivo and protected against the
      development of experimental autoimmune encephalomyelitis. Therefore, despite
      bearing predictive hallmarks of pathogenic effector function, previously Foxp3(+)
      iTregs have much lower proinflammatory potential than that of MBP-responsive Th1
      cells. Our results demonstrate that autoprotective versus autoaggressive
      functions in iTregs are not simply a binary relationship to be determined by
      their relative expression of Foxp3 versus T-bet and IFN-gamma.

PMID- 21084663
TI  - CD8+ T cells negatively regulate IL-4-dependent, IgG1-dominant posttransplant
      alloantibody production.
AB  - We have previously reported that CD8(+) T cells significantly influence Ab
      production based on the observation that posttransplant alloantibody levels in
      CD8-deficient murine hepatocyte transplant recipients are markedly enhanced.
      However, the precise mechanisms contributing to enhanced alloantibody production
      in the absence of CD8(+) T cells is not understood. We hypothesized that
      alloactivated CD8(+) T cells inhibit Ab production by skewing toward a
      proinflammatory cytokine profile, whereas when these cells are absent, an anti
      inflammatory cytokine profile shifts the alloimmune response toward alloantibody
      production. To investigate this possibility, alloantibody isotype profiles were
      examined in CD8-deficient and wild-type hepatocyte recipients. We found that IgG1
      (IL-4-dependent isotype) was the dominant alloantibody isotype in wild-type
      recipients as well as in CD8-deficient recipients, although the amount of
      alloantibody in the latter group was substantially higher. Utilizing real-time
      PCR we found that CD4(+) T cells from wild-type recipients significantly
      upregulated IFN-gamma but not IL-4 mRNA. In contrast, in the absence of CD8(+) T
      cells, CD4(+) T cells switched to significantly upregulate IL-4 mRNA, while IFN
      gamma was downregulated. IL-4 knockout mice do not produce any posttransplant
      alloantibody. However, adoptive transfer of wild-type CD4(+) T cells into CD8
      depleted IL-4 knockout mice restores high alloantibody levels observed in CD8
      depleted wild-type recipients. This suggests that IL-4-producing CD4(+) T cells
      are critical for posttransplant alloantibody production. Additionally, this CD8
      mediated regulation of posttransplant alloantibody production is IFN-gamma
      dependent. Further elucidation of the mechanisms by which CD8(+) T cells
      influence Ab production will significantly contribute to development of therapies
      to manipulate humoral responses to Ag.

PMID- 21084664
TI  - Efficient lung recruitment of respiratory syncytial virus-specific Th1 cells
      induced by recombinant bacillus Calmette-Guerin promotes virus clearance and
      protects from infection.
AB  - Infection by the respiratory syncytial virus (RSV) can cause extensive
      inflammation and lung damage in susceptible hosts due to a Th2-biased immune
      response. Such a deleterious inflammatory response can be enhanced by
      immunization with formalin- or UV-inactivated RSV, as well as with vaccinia virus
      expressing the RSV-G protein. Recently, we have shown that vaccination with rBCG
      expressing RSV Ags can prevent the disease in the mouse. To further understand
      the immunological mechanisms responsible for protection against RSV, we have
      characterized the T cell populations contributing to virus clearance in mice
      immunized with this BCG-based vaccine. We found that both CD4(+) and CD8(+) T
      cells were recruited significantly earlier to the lungs of infected mice that
      were previously vaccinated. Furthermore, we observed that simultaneous adoptive
      transfer of CD8(+) and CD4(+) RSV-specific T cells from vaccinated mice was
      required to confer protection against virus infection in naive recipients. In
      addition, CD4(+) T cells induced by vaccination released IFN-gamma after RSV
      challenge, indicating that protection is mediated by a Th1 immune response. These
      data suggest that vaccination with rBCG-expressing RSV Ags can induce a specific
      effector/memory Th1 immune response consisting on CD4(+) and CD8(+) T cells, both
      necessary for a fully protective response against RSV. These results support the
      notion that an effective induction of Th1 T cell immunity against RSV during
      childhood could counteract the unbalanced Th2-like immune response triggered by
      the natural RSV infection.

PMID- 21084665
TI  - Characterization of fish IRF3 as an IFN-inducible protein reveals evolving
      regulation of IFN response in vertebrates.
AB  - In mammals, IFN regulatory factor (IRF) 3 is a critical player in modulating
      transcription of type I IFN and IFN-stimulated genes (ISGs). In this study, we
      describe the roles of crucian carp (Carassius auratus L.) IRF3 in activating fish
      IFN and ISGs. Fish IRF3 exhibits a large sequence divergence from mammalian
      orthologs. Whereas mammalian IRF3 is constitutively expressed, fish IRF3 protein
      is significantly upregulated by IFN, poly-IC, and other stimuli known as IFN
      inducers in mammals. The IFN-inducible property of fish IRF3 is consistent with
      the comparative analysis of 5' flanking regulatory region of vertebrate IRF3
      genes, which reveals the presence of typical IFN-stimulated response elements in
      fish and amphibians, but an absence in tetrapods. Furthermore, either IFN or poly
      IC induces phosphorylation and cytoplasmic-to-nuclear translocation of IRF3,
      which seems essential for its function in that phosphomimic active IRF3 exhibits
      stronger transactivation than wild type IRF3. Finally, overexpression of fish
      IRF3 activates production of IFN that in turn triggers ISG transcription through
      Stat1 pathway, whereas transfection of dominant negative mutant IRF3-DN abrogates
      poly-IC induction of ISGs, probably owing to blockade of IFN production.
      Therefore, regulation of IFN response by vertebrate IRF3 is another ancient
      trait. These data provide evidence of the evolving function of vertebrate IRF3 on
      regulating IFN response.

PMID- 21084667
TI  - The first structures of T cell receptors bound to peptide-MHC.

PMID- 21084666
TI  - TNF receptor-associated factor 3 is required for T cell-mediated immunity and
      TCR/CD28 signaling.
AB  - We recently reported that TNFR-associated factor (TRAF)3, a ubiquitously
      expressed adaptor protein, promotes mature B cell apoptosis. However, the
      specific function of TRAF3 in T cells has remained unclear. In this article, we
      report the generation and characterization of T cell-specific TRAF3(-/-) mice, in
      which the traf3 gene was deleted from thymocytes and T cells. Ablation of TRAF3
      in the T cell lineage did not affect CD4 or CD8 T cell populations in secondary
      lymphoid organs or the numbers or proportions of CD4(+),CD8(+) or double-positive
      or double-negative thymocytes, except that the T cell-specific TRAF3(-/-) mice
      had a 2-fold increase in FoxP3(+) T cells. In striking contrast to mice lacking
      TRAF3 in B cells, the T cell TRAF3-deficient mice exhibited defective IgG1
      responses to a T-dependent Ag, as well as impaired T cell-mediated immunity to
      infection with Listeria monocytogenes. Surprisingly, we found that TRAF3 was
      recruited to the TCR/CD28 signaling complex upon costimulation and that TCR/CD28
      mediated proximal and distal signaling events were compromised by TRAF3
      deficiency. These findings provide insights into the roles played by TRAF3 in T
      cell activation and T cell-mediated immunity.

PMID- 21084668
TI  - Structure of the complex between human T-cell receptor, viral peptide and HLA-A2.
      Nature. 1996. 384: 134-141.

PMID- 21084669
TI  - An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR
      MHC complex. Science. 1996. 274: 209-219.

PMID- 21084671
TI  - Copy number variation modifies expression time courses.
AB  - A preliminary understanding into the phenotypic effect of DNA segment copy number
      variation (CNV) is emerging. These rearrangements were demonstrated to influence,
      in a somewhat dose-dependent manner, the expression of genes that map within
      them. They were also shown to modify the expression of genes located on their
      flanks and sometimes those at a great distance from their boundary. Here we
      demonstrate, by monitoring these effects at multiple life stages, that these
      controls over expression are effective throughout mouse development. Similarly,
      we observe that the more specific spatial expression patterns of CNV genes are
      maintained through life. However, we find that some brain-expressed genes mapping
      within CNVs appear to be under compensatory loops only at specific time points,
      indicating that the effect of CNVs on these genes is modulated during
      development. Notably, we also observe that CNV genes are significantly enriched
      within transcripts that show variable time courses of expression between strains.
      Thus, modifying the copy number of a gene may potentially alter not only its
      expression level, but also the timing of its expression.

PMID- 21084670
TI  - The role of the transcription factor CREB in immune function.
AB  - CREB is a transcription factor that regulates diverse cellular responses,
      including proliferation, survival, and differentiation. CREB is induced by a
      variety of growth factors and inflammatory signals and subsequently mediates the
      transcription of genes containing a cAMP-responsive element. Several immune
      related genes possess this cAMP-responsive element, including IL-2, IL-6, IL-10,
      and TNF-alpha. In addition, phosphorylated CREB has been proposed to directly
      inhibit NF-kappaB activation by blocking the binding of CREB binding protein to
      the NF-kappaB complex, thereby limiting proinflammatory responses. CREB also
      induces an antiapoptotic survival signal in monocytes and macrophages. In T and B
      cells, CREB activation promotes proliferation and survival and differentially
      regulates Th1, Th2, and Th17 responses. Finally, CREB activation is required for
      the generation and maintenance of regulatory T cells. This review summarizes
      current advances involving CREB in immune function--a role that is continually
      being defined.

PMID- 21084672
TI  - Enhanced angiotensin II-mediated central sympathoexcitation in streptozotocin
      induced diabetes: role of superoxide anion.
AB  - Studies have shown that the superoxide mechanism is involved in angiotensin II
      (ANG II) signaling in the central nervous system. We hypothesized that ANG II
      activates sympathetic outflow by stimulation of superoxide anion in the
      paraventricular nucleus (PVN) of streptozotocin (STZ)-induced diabetic rats. In
      alpha-chloralose- and urethane-anesthetized rats, microinjection of ANG II into
      the PVN (50, 100, and 200 pmol) produced dose-dependent increases in renal
      sympathetic nerve activity (RSNA), arterial pressure (AP), and heart rate (HR) in
      control and STZ-induced diabetic rats. There was a potentiation of the increase
      in RSNA (35.0 +/- 5.0 vs. 23.0 +/- 4.3%, P < 0.05), AP, and HR due to ANG II type
      I (AT(1)) receptor activation in diabetic rats compared with control rats.
      Blocking endogenous AT(1) receptors within the PVN with AT(1) receptor antagonist
      losartan produced significantly greater decreases in RSNA, AP, and HR in diabetic
      rats compared with control rats. Concomitantly, there were significant increases
      in mRNA and protein expression of AT(1) receptor with increased superoxide levels
      and expression of NAD(P)H oxidase subunits p22(phox), p47(phox), and p67(phox) in
      the PVN of rats with diabetes. Pretreatment with losartan (10 mg.kg(-1).day(-1)
      in drinking water for 3 wk) significantly reduced protein expression of NAD(P)H
      oxidase subunits (p22(phox) and p47(phox)) in the PVN of diabetic rats.
      Pretreatment with adenoviral vector-mediated overexpression of human cytoplasmic
      superoxide dismutase (AdCuZnSOD) within the PVN attenuated the increased central
      responses to ANG II in diabetes (RSNA: 20.4 +/- 0.7 vs. 27.7 +/- 2.1%, n = 6, P <
      0.05). These data support the concept that superoxide anion contributes to an
      enhanced ANG II-mediated signaling in the PVN involved with the exaggerated
      sympathoexcitation in diabetes.

PMID- 21084674
TI  - Nuclear membrane receptors for ET-1 in cardiovascular function.
AB  - Plasma membrane endothelin type A (ET(A)) receptors are internalized and recycled
      to the plasma membrane, whereas endothelin type B (ET(B)) receptors undergo
      degradation and subsequent nuclear translocation. Recent studies show that G
      protein-coupled receptors (GPCRs) and ion transporters are also present and
      functional at the nuclear membranes of many cell types. Similarly to other GPCRs,
      ET(A) and ET(B) are present at both the plasma and nuclear membranes of several
      cardiovascular cell types, including human cardiac, vascular smooth muscle,
      endocardial endothelial, and vascular endothelial cells. The distribution and
      density of ET(A)Rs in the cytosol (including the cell membrane) and the nucleus
      (including the nuclear membranes) differ between these cell types. However, the
      localization and density of ET-1 and ET(B) receptors are similar in these cell
      types. The extracellular ET-1-induced increase in cytosolic ([Ca](c)) and nuclear
      ([Ca](n)) free Ca(2+) is associated with an increase of cytosolic and nuclear
      reactive oxygen species. The extracellular ET-1-induced increase of [Ca](c) and
      [Ca](n) as well as intracellular ET-1-induced increase of [Ca](n) are cell-type
      dependent. The type of ET-1 receptor mediating the extracellular ET-1-induced
      increase of [Ca](c) and [Ca](n) depends on the cell type. However, the cytosolic
      ET-1-induced increase of [Ca](n) does not depend on cell type. In conclusion,
      nuclear membranes' ET-1 receptors may play an important role in overall ET-1
      action. These nuclear membrane ET-1 receptors could be targets for a new
      generation of antagonists.

PMID- 21084673
TI  - Modelflow underestimates cardiac output in heat-stressed individuals.
AB  - An estimation of cardiac output can be obtained from arterial pressure waveforms
      using the Modelflow method. However, whether the assumptions associated with
      Modelflow calculations are accurate during whole body heating is unknown. This
      project tested the hypothesis that cardiac output obtained via Modelflow
      accurately tracks thermodilution-derived cardiac outputs during whole body heat
      stress. Acute changes of cardiac output were accomplished via lower-body negative
      pressure (LBNP) during normothermic and heat-stressed conditions. In nine healthy
      normotensive subjects, arterial pressure was measured via brachial artery
      cannulation and the volume-clamp method of the Finometer. Cardiac output was
      estimated from both pressure waveforms using the Modeflow method. In normothermic
      conditions, cardiac outputs estimated via Modelflow (arterial cannulation: 6.1 +/
      1.0 l/min; Finometer 6.3 +/- 1.3 l/min) were similar with cardiac outputs
      measured by thermodilution (6.4 +/- 0.8 l/min). The subsequent reduction in
      cardiac output during LBNP was also similar among these methods. Whole body heat
      stress elevated internal temperature from 36.6 +/- 0.3 to 37.8 +/- 0.4 degrees C
      and increased cardiac output from 6.4 +/- 0.8 to 10.9 +/- 2.0 l/min when
      evaluated with thermodilution (P < 0.001). However, the increase in cardiac
      output estimated from the Modelflow method for both arterial cannulation (2.3 +/-
      1.1 l/min) and Finometer (1.5 +/- 1.2 l/min) was attenuated compared with
      thermodilution (4.5 +/- 1.4 l/min, both P < 0.01). Finally, the reduction in
      cardiac output during LBNP while heat stressed was significantly attenuated for
      both Modelflow methods (cannulation: -1.8 +/- 1.2 l/min, Finometer: -1.5 +/- 0.9
      l/min) compared with thermodilution (-3.8 +/- 1.19 l/min). These results
      demonstrate that the Modelflow method, regardless of Finometer or direct arterial
      waveforms, underestimates cardiac output during heat stress and during subsequent
      reductions in cardiac output via LBNP.

PMID- 21084675
TI  - Restoration of skeletal muscle leptin response does not precede the exercise
      induced recovery of insulin-stimulated glucose uptake in high-fat-fed rats.
AB  - Leptin administration increases fatty acid (FA) oxidation rates and decreases
      lipid storage in oxidative skeletal muscle, thereby improving insulin response.
      We have previously shown high-fat (HF) diets to rapidly induce skeletal muscle
      leptin resistance, prior to the disruption of normal muscle FA metabolism
      (increase in FA transport; accumulation of triacylglycerol, diacylglycerol,
      ceramide) that occurs in advance of impaired insulin signaling and glucose
      transport. All of this occurs within a 4-wk period. Conversely, exercise can
      rapidly improve insulin response, in as little as one exercise bout. Thus, if the
      early development of leptin resistance is a contributor to HF diet-induced
      insulin resistance (IR) in skeletal muscle, then it is logical to predict that
      the rapid restoration of insulin response by exercise training would be preceded
      by the recovery of leptin response. In the current study, we sought to determine
      1) whether 1, 2, or 4 wk of exercise training was sufficient to restore leptin
      response in isolated soleus muscle of rats already consuming a HF diet (60%
      kcal), and 2) whether this preceded the training-induced corrections in FA
      metabolism and improved insulin-stimulated glucose transport. In the low-fat (LF)
      fed control group, insulin increased glucose transport by 153% and leptin
      increased AMPK and ACC phosphorylation and the rate of palmitate oxidation
      (+73%). These responses to insulin and leptin were either severely blunted or
      absent following 4 wk of HF feeding. Exercise intervention decreased muscle
      ceramide content (-28%) and restored insulin-stimulated glucose transport to
      control levels within 1 wk; muscle leptin response (AMPK and ACC phosphorylation,
      FA oxidation) was also restored, but not until the 2-wk time point. In
      conclusion, endurance exercise training is able to restore leptin response, but
      this does not appear to be a necessary precursor for the restoration of insulin
      response.

PMID- 21084676
TI  - Interactions between the consumption of a high-fat diet and fasting in the
      regulation of fatty acid oxidation enzyme gene expression: an evaluation of
      potential mechanisms.
AB  - The consumption of high-fat diets (HFDs) and fasting are known to increase the
      expression of enzymes involved in fatty acid oxidation (FAO). However, it has
      been reported that the ability of physiological stressors to induce enzymes of
      FAO in skeletal muscle is blunted with obesity. In this regard, we sought to
      explore the effects and potential mechanisms of an HFD on the expression of FAO
      enzymes in the fed and fasted state. The consumption of an HFD increased the mRNA
      expression or protein content of medium-chain acyl-CoA dehydrogenase (MCAD),
      uncoupling protein-3 (UCP3), and pyruvate dehydrogenase kinase 4 (PDK4) in the
      fed state. Fasting increased the mRNA expression of PDK4, MCAD, and UCP-3, and
      the protein content of UCP-3 in chow but not HFD rats. HFDs did not increase
      carnitine palmitoyl transfer-1 (CPT-1) mRNA levels in the fed state and the
      effects of fasting were markedly reduced compared with chow-fed rats. The
      expression of peroxisome-proliferator-activated receptor-gamma coactivator-1beta
      (PGC-1beta) was increased in muscle from HFD rats in the fed state, while PGC-1
      related coactivator (PRC) was increased with fasting in chow-fed but not HFD
      rats. Plasma fatty acid levels were elevated in the fed state from HFD rats but
      not increased further with fasting, whereas fasting increased plasma fatty acids
      in chow-fed animals. Fasting-mediated increases in plasma epinephrine, and the
      activation of PKA and AMPK in skeletal muscle were similar between chow and HFD
      rats. p38 MAPK phosphorylation was increased with fasting in chow-fed but not HFD
      rats. Our findings suggest that a blunted effect of fasting on the induction of
      PDK4, MCAD, and UCP3 in skeletal muscle from HFD rats is likely a result of
      already elevated levels of these enzymes, the induction of which is associated
      with increases in plasma fatty acid and PGC-1beta. On the other hand, a blunted
      induction of PRC and CPT-1 mRNA may be explained by decreases in p38 MAPK
      signaling.

PMID- 21084677
TI  - Changes in ventral respiratory column GABAaR epsilon- and delta-subunits during
      hibernation mediate resistance to depression by EtOH and pentobarbital.
AB  - During hibernation in the 13-lined ground squirrel, Ictidomys tridecemlineatus,
      the cerebral cortex is electrically silent, yet the brainstem continues to
      regulate cardiorespiratory function. Previous work showed that neurons in slices
      through the medullary ventral respiratory column (VRC) but not the cortex are
      insensitive to high doses of pentobarbital during hibernation, leading to the
      hypothesis that GABA(A) receptors (GABA(A)R) in the VRC undergo a seasonal
      modification in subunit composition. To test whether alteration of GABA(A)R
      subunits are responsible for hibernation-associated pentobarbital insensitivity,
      we examined an array of subunits using RT-PCR and Western blots and identified
      changes in epsilon- and delta-subunits in the medulla but not the cortex. Using
      immunohistochemistry, we confirmed that during hibernation, the expression of
      epsilon-subunit-containing GABA(A)Rs nearly doubles in the VRC. We also
      identified a population of delta-subunit-containing GABA(A)Rs adjacent to the VRC
      that were differentially expressed during hibernation. As delta-subunit
      containing GABA(A)Rs are particularly sensitive to ethanol (EtOH), multichannel
      electrodes were inserted in slices of medulla and cortex from hibernating
      squirrels and EtOH was applied. EtOH, which normally inhibits neuronal activity,
      excited VRC but not cortical neurons during hibernation. This excitation was
      prevented by bicuculline pretreatment, indicating the involvement of GABA(A)Rs.
      We propose that neuronal activity in the VRC during hibernation is unaffected by
      pentobarbital due to upregulation of epsilon-subunit-containing GABA(A)Rs on VRC
      neurons. Synaptic input from adjacent inhibitory interneurons that express delta
      subunit-containing GABA(A)Rs is responsible for the excitatory effects of EtOH on
      VRC neurons during hibernation.

PMID- 21084678
TI  - Key roles of endothelin-1 and p38 MAPK in the regulation of atrial stretch
      response.
AB  - Mechanisms regulating stretch response in the left ventricle are investigated in
      detail but not well understood in atrial myocardium. Hypertrophic growth of
      atrial myocardium contributes to the pathogenesis of atrial fibrillation. In this
      study, we sought to elucidate mechanisms of stretch-induced activation of key
      signaling pathways and hypertrophy-associated genes in rat atria. Stretching of
      isolated atria induced a rapid increase in phosphorylation of p38 MAPK and ERK
      and induced a p38 MAPK-dependent increase in DNA binding activity of
      transcription factors Elk-1 and GATA-4. Inhibition of the ERK pathway had no
      effect on the cardiac transcription factors studied. Stretch-induced increase in
      atrial contractile function was substantially enhanced by inhibition of p38 MAPK.
      p38 MAPK also regulated stretch-induced increase in c-fos, beta-myosin heavy
      chain, B-type natriuretic peptide mRNA levels, and atrial natriuretic peptide
      secretion in isolated atria. Various autocrine/paracrine factors are known to
      mediate the stretch response in the left ventricle. Stretching of isolated atria
      resulted in a robust increase in endothelin-1 (ET-1) mRNA levels, while apelin
      and adrenomedullin signaling cascades were downregulated. Administration of mixed
      ET(A/B) receptor antagonist bosentan attenuated the stretch-induced activation of
      GATA-4 in isolated atria, whereas ANG II receptor type-1 antagonist CV-11974 had
      no effect. Moreover, analysis of RNA from intact atrial and ventricular
      myocardium revealed significantly higher mRNA levels of ET(A) receptor and ET
      converting enzyme-1 in atrial compared with ventricular myocardium. In
      conclusion, our findings identify the local ET-1 system and p38 MAPK as key
      regulators of load-induced hypertrophic response in isolated rat atria.

PMID- 21084679
TI  - Analytical construct of reversible desensitization of pituitary-testicular
      signaling: illustrative application in aging.
AB  - Luteinizing hormone (LH) administered in pharmacological amounts downregulates
      Leydig cell steroidogenesis. Whether reversible downregulation of physiological
      gonadotropin drive operates in vivo is unknown. Most of the analytical models of
      dose-response functions that have been constructed are biased by the assumption
      that no downregulation exists. The present study employs a new analytical
      platform to quantify potential (but not required) pulsatile cycles of LH
      testosterone (T) dose-response stimulation, desensitization, and recovery (pulse
      by-pulse hysteresis) in 26 healthy men sampled every 10 min for 24 h. A
      sensitivity-downregulation hysteresis construct predicted marked hysteresis with
      a median time delay to LH dose-response inflection within individual T pulses of
      23 min and with median T pulse onset and recovery LH sensitivities of 1.1 and
      0.10 slope unit, respectively (P < 0.001). A potency-downregulation model yielded
      median estimates of one-half maximally stimulatory LH concentrations (EC(50)
      values) of 0.66 and 7.5 IU/l for onset and recovery, respectively (P < 0.001). An
      efficacy-downregulation formulation of hysteresis forecasts median LH efficacies
      of 20 and 8.3 ng.dl(-1).min(-1) for onset and offset of T secretory burst,
      respectively (P = 0.002). Segmentation of the LH-T data by age suggested greater
      sensitivity, higher EC(50) (increased LH potency), and markedly (2.7-fold)
      attenuated LH efficacy in older individuals. Each of the three hysteresis models
      yielded a marked (P < 0.005) reduction in estimated model residual error compared
      with no hysteresis. In summary, model-based analyses allowing for (but not
      requiring) reversible pituitary-gonadal effector-response downregulation are
      consistent with a hypothesis of recurrent, brief cycles of LH-dependent
      stimulation, desensitization, and recovery of pulsatile T secretion in vivo and
      an age-associated reduction of LH efficacy. Prospective studies would be required
      to prove this aging effect.

PMID- 21084680
TI  - Differential expression of Na+-Cl- cotransporter and Na+-K+-Cl- cotransporter 2
      in the distal nephrons of euryhaline and seawater pufferfishes.
AB  - The process of NaCl reabsorption in the distal nephron allows freshwater fishes
      to excrete hypotonic urine and seawater fishes to excrete urine containing high
      concentrations of divalent ions; the relevant transporters, however, have not yet
      been identified. In the mammalian distal nephron, NaCl absorption is mediated by
      Na(+)-K(+)-Cl(-) cotransporter 2 (NKCC2, Slc12a1) in the thick ascending limb,
      Na(+)-Cl(-) cotransporter (NCC, Slc12a3) in the distal convoluted tubule, and
      epithelial sodium channel (ENaC) in the collecting duct. In this study, we
      compared the expression profiles of these proteins in the kidneys of euryhaline
      and seawater pufferfishes. Mining the fugu genome identified one NKCC2 gene and
      one NCC gene, but no ENaC gene. RT-PCR and in situ hybridization analyses
      demonstrated that NKCC2 was highly expressed in the distal tubules and NCC was
      highly expressed in the collecting ducts of euryhaline pufferfish (mefugu,
      Takifugu obscurus). On the other hand, the kidney of seawater pufferfish
      (torafugu, Takifugu rubripes), which lacked distal tubules, expressed very low
      levels of NCC, and, in the collecting ducts, high levels of NKCC2. Acclimation of
      mefugu to seawater resulted in a 2.7* decrease in NCC expression, whereas NKCC2
      expression was not markedly affected. Additionally, internalization of NCC from
      the apical surface of the collecting ducts was observed. These results suggest
      that NaCl reabsorption in the distal nephron of the fish kidney is mediated by
      NCC and NKCC2 in freshwater and by NKCC2 in seawater.

PMID- 21084681
TI  - Visual suppression in the superior colliculus around the time of microsaccades.
AB  - Miniature eye movements jitter the retinal image unceasingly, raising the
      question of how perceptual continuity is achieved during visual fixation. Recent
      work discovered suppression of visual bursts in the superior colliculus around
      the time of microsaccades, tiny jerks of the eyes that support visual perception
      while gaze is fixed. This finding suggests that corollary discharge, supporting
      visual stability when rapid eye movements drastically shift the retinal image,
      may also exist for the smallest saccades.

PMID- 21084682
TI  - Neuronal sodium leak channel is responsible for the detection of sodium in the
      rat median preoptic nucleus.
AB  - Sodium (Na(+)) ions are of primary importance for hydromineral and cardiovascular
      homeostasis, and the level of Na(+) in the body fluid compartments [plasma and
      cerebrospinal fluid (CSF)] is precisely monitored in the hypothalamus. Glial
      cells seem to play a critical role in the mechanism of Na(+) detection. However,
      the precise role of neurons in the detection of extracellular Na(+) concentration
      ([Na(+)](out)) remains unclear. Here we demonstrate that neurons of the median
      preoptic nucleus (MnPO), a structure in close contact with the CSF, are specific
      Na(+) sensors. Electrophysiological recordings were performed on dissociated rat
      MnPO neurons under isotonic [Na(+)] (100 mM NaCl) with local application of
      hypernatriuric (150, 180 mM NaCl) or hyponatriuric (50 mM NaCl) external
      solution. The hyper- and hyponatriuric conditions triggered an in- and an outward
      current, respectively. The reversal potential of the current matched the
      equilibrium potential of Na(+), indicating that a change in [Na(+)](out) modified
      the influx of Na(+) in the MnPO neurons. The conductance of the Na(+) current was
      not affected by either the membrane potential or the [Na(+)](out). Moreover, the
      channel was highly selective for lithium over guanidinium. Together, these data
      identified the channel as a Na(+) leak channel. A high correlation between the
      electrophysiological recordings and immunofluorescent labeling for the Na(X)
      channel in dissociated MnPO neurons strongly supports this channel as a candidate
      for the Na(+) leak channel responsible for the Na(+)-sensing ability of rat MnPO
      neurons. The absence of Na(X) labeling and of a specific current evoked by a
      change in [Na(+)](out) in mouse MnPO neurons suggests species specificity in the
      hypothalamus structures participating in central Na(+) detection.

PMID- 21084683
TI  - Preferred locomotor phase of activity of lumbar interneurons during air-stepping
      in subchronic spinal cats.
AB  - Spinal locomotor circuits are intrinsically capable of driving a variety of
      behaviors such as stepping, scratching, and swimming. Based on an observed
      rostrocaudal wave of activity in the motoneuronal firing during locomotor tasks,
      the traveling-wave hypothesis proposes that spinal interneuronal firing follows a
      similar rostrocaudal pattern of activation, suggesting the presence of spatially
      organized interneuronal modules within the spinal motor system. In this study, we
      examined if the spatial organization of the lumbar interneuronal activity
      patterns during locomotor activity in the adult mammalian spinal cord was
      consistent with a traveling-wave organizational scheme. The activity of spinal
      interneurons within the lumbar intermediate zone was examined during air-stepping
      in subchronic spinal cats. The preferred phase of interneuronal activity during a
      step cycle was determined using circular statistics. We found that the preferred
      phases of lumbar interneurons from both sides of the cord were evenly distributed
      over the entire step cycle with no indication of functional groupings. However,
      when units were subcategorized according to spinal hemicords, the preferred
      phases of units on each side largely fell around the period of extensor muscle
      activity on each side. In addition, there was no correlation between the
      preferred phases of units and their rostrocaudal locations along the spinal cord
      with preferred phases corresponding to both flexion and extension phases of the
      step cycle found at every rostrocaudal level of the cord. These results are
      consistent with the hypothesis that interneurons operate as part of a
      longitudinally distributed network rather than a rostrocaudally organized
      traveling-wave network.

PMID- 21084684
TI  - Common synaptic input to the human hypoglossal motor nucleus.
AB  - The tongue plays a key role in various volitional and automatic functions such as
      swallowing, maintenance of airway patency, and speech. Precisely how hypoglossal
      motor neurons, which control the tongue, receive and process their often
      concurrent input drives is a subject of ongoing research. We investigated common
      synaptic input to the hypoglossal motor nucleus by measuring the coordination of
      spike timing, firing rate, and oscillatory activity across motor units recorded
      from unilateral (i.e., within a belly) or bilateral (i.e., across both bellies)
      locations within the genioglossus (GG), the primary protruder muscle of the
      tongue. Simultaneously recorded pairs of motor units were obtained from 14
      healthy adult volunteers using tungsten microelectrodes inserted percutaneously
      into the GG while the subjects were engaged in volitional tongue protrusion or
      rest breathing. Bilateral motor unit pairs showed concurrent low frequency
      alterations in firing rate (common drive) with no significant difference between
      tasks. Unilateral motor unit pairs showed significantly stronger common drive in
      the protrusion task compared with rest breathing, as well as higher indices of
      synchronous spiking (short-term synchrony). Common oscillatory input was assessed
      using coherence analysis and was observed in all conditions for frequencies up to
      ~ 5 Hz. Coherence at frequencies up to ~ 10 Hz was strongest in motor unit pairs
      recorded from the same GG belly in tongue protrusion. Taken together, our results
      suggest that cortical drive increases motor unit coordination within but not
      across GG bellies, while input drive during rest breathing is distributed
      uniformly to both bellies of the muscle.

PMID- 21084685
TI  - Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel
      fiber synapses.
AB  - Endocannabinoids are potent regulators of synaptic strength. They are generally
      thought to modify neurotransmitter release through retrograde activation of
      presynaptic type 1 cannabinoid receptors (CB1Rs). In the cerebellar cortex, CB1Rs
      regulate several forms of synaptic plasticity at synapses onto Purkinje cells,
      including presynaptically expressed short-term plasticity and, somewhat
      paradoxically, a postsynaptic form of long-term depression (LTD). Here we have
      generated mice in which CB1Rs were selectively eliminated from cerebellar granule
      cells, whose axons form parallel fibers. We find that in these mice,
      endocannabinoid-dependent short-term plasticity is eliminated at parallel fiber,
      but not inhibitory interneuron, synapses onto Purkinje cells. Further, parallel
      fiber LTD is not observed in these mice, indicating that presynaptic CB1Rs
      regulate long-term plasticity at this synapse.

PMID- 21084686
TI  - Regression-based identification of behavior-encoding neurons during large-scale
      optical imaging of neural activity at cellular resolution.
AB  - The advent of methods for optical imaging of large-scale neural activity at
      cellular resolution in behaving animals presents the problem of identifying
      behavior-encoding cells within the resulting image time series. Rapid and precise
      identification of cells with particular neural encoding would facilitate targeted
      activity measurements and perturbations useful in characterizing the operating
      principles of neural circuits. Here we report a regression-based approach to
      semiautomatically identify neurons that is based on the correlation of
      fluorescence time series with quantitative measurements of behavior. The approach
      is illustrated with a novel preparation allowing synchronous eye tracking and two
      photon laser scanning fluorescence imaging of calcium changes in populations of
      hindbrain neurons during spontaneous eye movement in the larval zebrafish.
      Putative velocity-to-position oculomotor integrator neurons were identified that
      showed a broad spatial distribution and diversity of encoding. Optical
      identification of integrator neurons was confirmed with targeted loose-patch
      electrical recording and laser ablation. The general regression-based approach we
      demonstrate should be widely applicable to calcium imaging time series in
      behaving animals.

PMID- 21084688
TI  - Synaptic interactions underlying synchronized inhibition in the basal amygdala:
      evidence for existence of two types of projection cells.
AB  - The basal amygdala (BA) plays a key role in mediating the facilitating effects of
      emotions on memory. Recent findings indicate that this function depends on the
      ability of BA neurons to generate coherent oscillatory activity, facilitating
      synaptic plasticity in target neurons. However, the mechanisms allowing BA
      neurons to synchronize their activity remain poorly understood. Here, we aimed to
      shed light on this question, focusing on a slow periodic inhibitory oscillation
      previously observed in the BA in vitro. Paired patch recordings showed that these
      large inhibitory postsynaptic potentials (IPSPs) occur almost synchronously in BA
      projection neurons, that they were typically not preceded by excitatory
      postsynaptic potentials (EPSPs), and that they had little or no correlate in
      neighboring amygdala nuclei or cortical fields. The initial phase of the IPSPs
      was associated with an increase in membrane potential fluctuations at 50-100 Hz.
      In keeping with this, the IPSPs seen in projection cells were correlated with
      repetitive firing at 50-100 Hz in presumed interneurons and they could be
      abolished by picrotoxin. However, the IPSPs were also sensitive to 6-cyano-7
      nitroquinoxaline-2,3-dione, implying that they arose from the interplay between
      glutamatergic and GABAergic BA neurons. In support of this idea, we identified a
      small subset of projection cells (15%), positively identified as such by
      retrograde labeling from BA projection sites, that began firing shortly before
      the IPSP onset and presumably drove interneuronal firing. These results add to a
      rapidly growing body of data indicating that the BA contains at least two
      distinct types of projection cells that vary in their relation with interneurons
      and extra-amygdala targets.

PMID- 21084687
TI  - Location of release sites and calcium-activated chloride channels relative to
      calcium channels at the photoreceptor ribbon synapse.
AB  - Vesicle release from photoreceptor ribbon synapses is regulated by L-type Ca(2+)
      channels, which are in turn regulated by Cl(-) moving through calcium-activated
      chloride [Cl(Ca)] channels. We assessed the proximity of Ca(2+) channels to
      release sites and Cl(Ca) channels in synaptic terminals of salamander
      photoreceptors by comparing fast (BAPTA) and slow (EGTA) intracellular Ca(2+)
      buffers. BAPTA did not fully block synaptic release, indicating some release
      sites are <100 nm from Ca(2+) channels. Comparing Cl(Ca) currents with predicted
      Ca(2+) diffusion profiles suggested that Cl(Ca) and Ca(2+) channels average a few
      hundred nanometers apart, but the inability of BAPTA to block Cl(Ca) currents
      completely suggested some channels are much closer together. Diffuse
      immunolabeling of terminals with an antibody to the putative Cl(Ca) channel
      TMEM16A supports the idea that Cl(Ca) channels are dispersed throughout the
      presynaptic terminal, in contrast with clustering of Ca(2+) channels near
      ribbons. Cl(Ca) currents evoked by intracellular calcium ion concentration
      ([Ca(2+)](i)) elevation through flash photolysis of DM-nitrophen exhibited EC(50)
      values of 556 and 377 nM with Hill slopes of 1.8 and 2.4 in rods and cones,
      respectively. These relationships were used to estimate average submembrane
      [Ca(2+)](i) in photoreceptor terminals. Consistent with control of exocytosis by
      [Ca(2+)] nanodomains near Ca(2+) channels, average submembrane [Ca(2+)](i)
      remained below the vesicle release threshold (~ 400 nM) over much of the
      physiological voltage range for cones. Positioning Ca(2+) channels near release
      sites may improve fidelity in converting voltage changes to synaptic release. A
      diffuse distribution of Cl(Ca) channels may allow Ca(2+) influx at one site to
      influence relatively distant Ca(2+) channels.

PMID- 21084690
TI  - Upholding professionalism: the disciplinary process of the American Academy of
      Neurology.
AB  - OBJECTIVE: To review the disciplinary process by which the American Academy of
      Neurology (AAN) enforces its formalized standards of professional conduct.
      METHODS: We reviewed the AAN's Disciplinary Action Policy. We tracked the elapsed
      time from receipt to final decision of all allegations ("complaints") of improper
      conduct by AAN members submitted from 2004 to 2009. We placed each complaint into
      1 of 4 categories: allegations of 1) improper expert witness testimony; 2)
      substandard care; 3) unprofessional conduct; 4) or both 2 and 3. We noted the
      type of complainant (AAN member or nonmember) and the final outcome for each
      complaint. RESULTS: The AAN's disciplinary process is a 5-step procedure with
      multiple reviewing bodies. From 2004 to 2009, the AAN received 3-16 complaints
      per year (total 58), with 16 filed each year in 2008 and 2009. Thirty-one
      complaints (53%) were submitted by nonmembers and 27 (47%) by members.
      Disciplinary action was recommended for 6 complaints (10.3%) with action taken in
      3 (5.1%) and the member resigning in lieu of action in 3 (5.1%). The average
      number of days from receipt of complaint to final decision was 537, with an
      average of 890 days from 2004 to 2006, decreased to 184 days from 2007 to 2009.
      CONCLUSIONS: Recent revisions to the disciplinary process have increased
      efficiency and enhanced procedural safeguards. The AAN determined a mean of 12
      months, from receipt of complaint to final decision rendered, is an appropriate
      benchmark when handling complaints. The AAN's disciplinary process upholds
      standards of professional conduct for AAN members and protects members from
      unsubstantiated complaints.

PMID- 21084689
TI  - Graded reductions in oxygenation evoke graded reconfiguration of the isolated
      respiratory network.
AB  - Neurons depend on aerobic metabolism, yet are very sensitive to oxidative stress
      and, as a consequence, typically operate in a low O(2) environment. The balance
      between blood flow and metabolic activity, both of which can vary spatially and
      dynamically, suggests that local O(2) availability markedly influences network
      output. Yet the understanding of the underlying O(2)-sensing mechanisms is
      limited. Are network responses regulated by discrete O(2)-sensing mechanisms or,
      rather, are they the consequence of inherent O(2) sensitivities of mechanisms
      that generate the network activity? We hypothesized that a broad range of O(2)
      tensions progressively modulates network activity of the pre-Botzinger complex
      (preBotC), a neuronal network critical to the central control of breathing.
      Rhythmogenesis was measured from the preBotC in transverse neonatal mouse brain
      stem slices that were exposed to graded reductions in O(2) between 0 and 95%
      O(2), producing tissue oxygenation values ranging from 20 +/- 18 (mean +/- SE) to
      440 +/- 56 Torr at the slice surface, respectively. The response of the preBotC
      to graded changes in O(2) is progressive for some metrics and abrupt for others,
      suggesting that different aspects of the respiratory network have different
      sensitivities to O(2).

PMID- 21084691
TI  - The AAN disciplinary process: indispensable to neurologists.

PMID- 21084693
TI  - Suppressor of cytokine signaling 1 (SOCS1) limits NFkappaB signaling by
      decreasing p65 stability within the cell nucleus.
AB  - Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytoplasmic
      Janus kinases (Jak) and signal transducer and activator of transcription (STAT)
      signaling pathways. Previously the authors surprisingly observed that SOCS1
      translocated into the nucleus, which was because of the presence of a nuclear
      localization sequence. This report now hypothesizes that SOCS1 mediates specific
      functions within the nuclear compartment because it is instantly transported into
      the nucleus, as shown by photoactivation and live cell imaging in human HEK293
      cells. The NFkappaB component p65 is identified as an interaction partner for
      SOCS1 but not for other members of the SOCS family. SOCS1 bound to p65 only
      within the nucleus. By means of its SOCS box domain, SOCS1 operated as a
      ubiquitin ligase, leading to polyubiquitination and proteasomal degradation of
      nuclear p65. Thus, SOCS1 limited prolonged p65 signaling and terminated
      expression of NFkappaB inducible genes. Using mutants that lack either nuclear
      translocation or a functional SOCS box, this report identifies genes that are
      regulated in a manner dependent on the nuclear availability of SOCS1. Data show
      that beyond its receptor-proximal function in Jak/STAT signaling, SOCS1 also
      regulates the duration of NFkappaB signaling within the cell nucleus, thus
      exerting a heretofore unrecognized function.

PMID- 21084692
TI  - Racial/ethnic disparities in access to physician care and medications among US
      stroke survivors.
AB  - BACKGROUND: Mexican Americans and non-Hispanic blacks have higher stroke
      recurrence rates and lower rates of secondary stroke prevention than non-Hispanic
      whites. As a potential explanation for this disparity, we assessed racial/ethnic
      differences in access to physician care and medications in a national sample of
      US stroke survivors. METHODS: Among all 4,864 stroke survivors aged>=45 years who
      responded to the National Health Interview Survey years 2000-2006, we compared
      access to care within the last 12 months by race/ethnicity before and after
      stratification by age (45-64 years vs >=65 years). With logistic regression, we
      adjusted associations between access measures and race/ethnicity for sex,
      comorbidity, neurologic disability, health status, year, income, and health
      insurance. RESULTS: Among stroke survivors aged 45-64 years, Mexican Americans,
      non-Hispanic blacks, and non-Hispanic whites reported similar rates of no
      generalist physician visit (approximately 15%) and inability to afford
      medications (approximately 20%). However, among stroke survivors aged>=65 years,
      Mexican Americans and blacks, compared with whites, reported greater frequency of
      no generalist visit (15%, 12%, 8%; p=0.02) and inability to afford medications
      (20%, 11%, 6%; p<0.001). Mexican Americans and blacks more frequently reported no
      medical specialist visit (54%, 49%, 40%; p<0.001) than did whites and rates did
      not differ by age. Full covariate adjustment did not fully explain these
      racial/ethnic differences. CONCLUSIONS: Among US stroke survivors at least 65
      years old, Mexican Americans and blacks reported worse access to physician care
      and medications than whites. This reduced access may lead to inadequate risk
      factor modification and recurrent stroke in these high-risk minority groups.

PMID- 21084694
TI  - Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+
      channel polarized trafficking in vivo.
AB  - Targeted deletion of the Kcne2 potassium channel beta subunit gene ablates
      gastric acid secretion and predisposes to gastric neoplasia in mice. Here, we
      discovered that Kcne2 deletion basolaterally reroutes the Kcnq1 alpha subunit in
      vivo in parietal cells (PCs), in which the normally apical location of the Kcnq1
      Kcne2 channel facilitates its essential role in gastric acid secretion.
      Quantitative RT-PCR and Western blotting revealed that Kcne2 deletion remodeled
      fundic Kcne3 (2.9+/-0.8-fold mRNA increase, n=10; 5.3+/-0.4-fold protein
      increase, n=7) but not Kcne1, 4, or 5, and resulted in basolateral Kcnq1-Kcne3
      complex formation in Kcne2(-/-) PCs. Concomitant targeted deletion of Kcne3
      (creating Kcne2(-/-)Kcne3(-/-) mice) restored PC apical Kcnq1 localization
      without Kcne1, 4, or 5 remodeling (assessed by quantitative RT-PCR; n=5-10),
      indicating Kcne3 actively, basolaterally rerouted Kcnq1 in Kcne2(-/-) PCs.
      Despite this, Kcne3 deletion exacerbated gastric hyperplasia in Kcne2(-/-) mice,
      and both hypochlorhydria and hyperplasia in Kcne2(+/-) mice, suggesting that
      Kcne3 up-regulation was beneficial in Kcne2-depleted PCs. The findings reveal, in
      vivo, Kcne-dependent alpha subunit polarized trafficking and the existence and
      consequences of potassium channel beta subunit remodeling.

PMID- 21084695
TI  - Global dynamic conformational changes in the suppressor domain of IP3 receptor by
      stepwise binding of the two lobes of calmodulin.
AB  - The roles of calmodulin (CaM) have been key points of controversy in the
      regulation of inositol-1,4,5-trisphosphate receptor (IP(3)R). To address the
      issue, we studied the interaction between CaM and the suppressor domain of
      IP(3)R, a key allosteric regulatory domain. First, by means of a pulldown and a
      fluorescence titration experiment, we confirmed the interaction. Through
      subsequent NMR binding experiments, we observed dramatic peak disappearances of
      the suppressor domain on interaction with apo-CaM. The data indicated that apo
      CaM induces large-scale dynamic conformational changes in the suppressor domain,
      involving partial unfolding and subdomain rearrangement. Analysis of the NMR data
      of CaM surprisingly revealed that its C lobe alone can cause such changes.
      Further binding experiments showed that calcium allows the free N lobe to bind to
      the suppressor domain, which induces extra conformational changes in both of the
      proteins. These results were also confirmed with CaM deletion mutants with either
      the N or C lobe. On the basis of this novel binding mechanism, we propose a model
      in which the partial unfolding of the suppressor domain by apo-CaM and the
      stepwise binding of the N lobe of CaM to the suppressor domain are important
      elements of calcium/CaM inhibition of IP(3)R. We believe that our working model
      encompasses previous regulation mechanisms of IP(3)R by calcium/CaM and provides
      new insights into the CaM-target interaction.

PMID- 21084696
TI  - Hypertrophic phenotype in cardiac cell assemblies solely by structural cues and
      ensuing self-organization.
AB  - In vitro models of cardiac hypertrophy focus exclusively on applying "external"
      dynamic signals (electrical, mechanical, and chemical) to achieve a hypertrophic
      state. In contrast, here we set out to demonstrate the role of "self-organized"
      cellular architecture and activity in reprogramming cardiac cell/tissue function
      toward a hypertrophic phenotype. We report that in neonatal rat cardiomyocyte
      culture, subtle out-of-plane microtopographic cues alter cell attachment,
      increase biomechanical stresses, and induce not only structural remodeling, but
      also yield essential molecular and electrophysiological signatures of
      hypertrophy. Increased cell size and cell binucleation, molecular up-regulation
      of released atrial natriuretic peptide, altered expression of classic hypertrophy
      markers, ion channel remodeling, and corresponding changes in
      electrophysiological function indicate a state of hypertrophy on par with other
      in vitro and in vivo models. Clinically used antihypertrophic pharmacological
      treatments partially reversed hypertrophic behavior in this in vitro model.
      Partial least-squares regression analysis, combining gene expression and
      functional data, yielded clear separation of phenotypes (control: cells grown on
      flat surfaces; hypertrophic: cells grown on quasi-3-dimensional surfaces and
      treated). In summary, structural surface features can guide cardiac cell
      attachment, and the subsequent syncytial behavior can facilitate trophic signals,
      unexpectedly on par with externally applied mechanical, electrical, and chemical
      stimulation.

PMID- 21084697
TI  - Oxidized low-density lipoprotein and atherosclerosis.

PMID- 21084698
TI  - Vitamin D3 suppresses immune reactions in atherosclerosis, affecting regulatory T
      cells and dendritic cell function.

PMID- 21084699
TI  - Ticagrelor to prevent restenosis: new drug for an old hypothesis?

PMID- 21084700
TI  - Is NAD(P)H oxidase a missing link for air pollution-enhanced obesity?

PMID- 21084701
TI  - n-6 and n-3 Fatty acids and atherosclerosis: ratios or amounts?

PMID- 21084702
TI  - Nuclear factor-{kappa}B-mediated regulation of telomerase: the Myc link.

PMID- 21084703
TI  - Is coronary artery calcification at the intersection of vitamin D and coronary
      artery disease?

PMID- 21084704
TI  - The Sixth Pacific Vascular Symposium: the venous ulcer summit.

PMID- 21084705
TI  - Platelets unplugged: an ATVB special series focused on platelet biology.

PMID- 21084707
TI  - mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish.
AB  - Macrophages and neutrophils play important roles during the innate immune
      response, phagocytosing invading microbes and delivering antimicrobial compounds
      to the site of injury. Functional analyses of the cellular innate immune response
      in zebrafish infection/inflammation models have been aided by transgenic lines
      with fluorophore-marked neutrophils. However, it has not been possible to study
      macrophage behaviors and neutrophil/macrophage interactions in vivo directly
      because there has been no macrophage-only reporter line. To remove this
      roadblock, a macrophage-specific marker was identified (mpeg1) and its promoter
      used in mpeg1-driven transgenes. mpeg1-driven transgenes are expressed in
      macrophage-lineage cells that do not express neutrophil-marking transgenes. Using
      these lines, the different dynamic behaviors of neutrophils and macrophages after
      wounding were compared side-by-side in compound transgenics.
      Macrophage/neutrophil interactions, such as phagocytosis of senescent
      neutrophils, were readily observed in real time. These zebrafish transgenes
      provide a new resource that will contribute to the fields of inflammation,
      infection, and leukocyte biology.

PMID- 21084706
TI  - Genetic regulation of platelet receptor expression and function: application in
      clinical practice and drug development.
AB  - Understanding genetic contributions to platelet function could have profound
      clinical ramifications for personalizing platelet-directed pharmacotherapy, by
      providing insight into the risks and possible benefits associated with specific
      genotypes. This article represents an integrated summary of presentations related
      to genetic regulation of platelet receptor expression and function given at the
      Fifth Annual Platelet Colloquium in January 2010. It is supplemented with
      additional highlights from the literature covering (1) approaches to determining
      and evidence for the associations of genetic variants with platelet hypo- and
      hyperresponsive phenotypes, (2) the ramifications of these polymorphisms with
      regard to clinical responses to antiplatelet therapies, and (3) the role of
      platelet function/genetic testing in guiding antiplatelet therapy.

PMID- 21084708
TI  - Sbds is required for Rac2-mediated monocyte migration and signaling downstream of
      RANK during osteoclastogenesis.
AB  - Shwachman-Diamond syndrome (SDS) results from mutations in the SBDS gene,
      characterized by exocrine pancreatic insufficiency and hematologic and skeletal
      abnormalities. Neutropenia and neutrophil dysfunction are hallmark features of
      SDS; however, causes for the bone defects are unknown. Dysfunction of bone
      resorbing osteoclasts, formed by the fusion of monocytic progenitors derived from
      the same granulocytic precursors as neutrophils, could be responsible. We report
      that Sbds is required for in vitro and in vivo osteoclastogenesis (OCG). Sbds
      null murine monocytes formed osteoclasts of reduced number and size because of
      impaired migration and fusion required for OCG. Phenotypically, Sbds-null mice
      exhibited low-turnover osteoporosis consistent with findings in SDS patients.
      Western blotting of Rho GTPases that control actin dynamics and migration showed
      a 5-fold decrease in Rac2, whereas Rac1, Cdc42, and RhoA were unchanged or only
      mildly reduced. Although migration was rescued on Rac2 supplementation, OCG was
      not. This was attributed to impaired signaling downstream of receptor activator
      of nuclear factor-kappaB (RANK) and reduced expression of the RANK-ligand
      dependent fusion receptor DC-STAMP. We conclude that Sbds is required for OCG by
      regulating monocyte migration via Rac2 and osteoclast differentiation signaling
      downstream of RANK. Impaired osteoclast formation could disrupt bone homeostasis,
      resulting in skeletal abnormalities seen in SDS patients.

PMID- 21084709
TI  - Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17
      secreting T cells.
AB  - Mucosal-associated invariant T (MAIT) cells are very abundant in humans and have
      antimicrobial specificity, but their functions remain unclear. MAIT cells are
      CD161(hi)IL-18Ralpha(+) and either CD4(-)CD8(-) (DN) or CD8alphabeta(int) T
      cells. We now show that they display an effector-memory phenotype (CD45RA(
      )CD45RO(+)CD95(hi)CD62L(lo)), and their chemokine receptor expression pattern
      (CCR9(int)CCR7(-)CCR5(hi)CXCR6(hi)CCR6(hi)) indicates preferential homing to
      tissues and particularly the intestine and the liver. MAIT cells can represent up
      to 45% of the liver lymphocytes. They produce interferon-gamma and Granzyme-B as
      well as high levels of interleukin-17 after phorbol myristate acetate + ionomycin
      stimulation. Most MAIT cells are noncycling cells (< 1% are Ki-67(+)) and express
      the multidrug resistance transporter (ABCB1). As expected from this phenotype,
      MAIT cells are more resistant to chemotherapy than other T-cell populations.
      These features might also allow MAIT cells to resist the xenobiotics potentially
      secreted by the gut bacteria. We also show that this population does not appear
      to have antiviral specificity and that CD8 MAIT cells include almost all the
      ABCB1(+)CD161(hi) CD8 T cells. Together with their already known abundance and
      antimicrobial specificity, the gut-liver homing characteristics, high expression
      of ABCB1, and ability to secrete interleukin-17 probably participate in the
      antibacterial properties of MAIT cells.

PMID- 21084710
TI  - PRKA/AMPK: integrating energy status with fertility in pituitary gonadotrophs.

PMID- 21084711
TI  - Characterization of the estrous cycle in Octodon degus.
AB  - We characterized the reproductive cycle of Octodon degus to determine whether
      reproductive maturation is spontaneous in juveniles and if ovarian cyclicity and
      luteal function are spontaneous in adults. Laboratory-reared prepubertal and
      adult females were monitored for vaginal patency and increased wheel-running.
      Sexual receptivity was assessed by pairing adult females with a male 1)
      continuously, 2) at the time of vaginal patency, or 3) following estradiol
      treatment. Blood samples were assayed for estradiol and progesterone
      concentrations on Days 1, 4, 8, and 16 relative to vaginal opening. Ovarian
      tissues were collected 6 and 16 days after behavioral estrus and 6 days after
      copulation for histology. In juveniles, the onset of cyclic vaginal patency and
      increased wheel-running activity was spontaneous, occurred in the absence of
      proximal male cues, and appeared at regular intervals (17.5 +/- 1.4 days). In
      adults, vaginal patency and increased wheel-running occurred cyclically (21.2 +/-
      0.6 days) in the absence of proximal male cues, and these traits predicted the
      time of sexual receptivity. Corpora lutea develop spontaneously and are
      maintained for 12-14 days. The ovaries had well-developed corpora lutea 6 days
      after mating and 6 days after estrus without mating. Progesterone concentrations
      were highest in the second half of the cycle when corpora lutea were present and
      estradiol concentrations peaked on the day of estrus. Thus, female degus appear
      to exhibit a spontaneous reproductive cycle consistent with other Hystricognathi
      rodents. Octodon degus is a novel model with which to examine the mechanisms
      underlying different reproductive cycles.

PMID- 21084712
TI  - Sertoli cells dictate spermatogonial stem cell niches in the mouse testis.
AB  - Sustained spermatogenesis in adult males relies on the activity of spermatogonial
      stem cells (SSCs). In general, tissue-specific stem cell populations such as SSCs
      are influenced by contributions of support cells that form niche
      microenvironments. Previous studies have provided indirect evidence that several
      somatic cell populations and the interstitial vasculature influence SSC
      functions, but an individual orchestrator of niches has not been described. In
      this study, functional transplantation of SSCs, in combination with experimental
      alteration of Sertoli cell content by polythiouracil (PTU)-induced transient
      hypothyroidism, was used to explore the relationship of Sertoli cells with SSCs
      in testes of adult mice. Transplantation of SSCs from PTU-treated donor mice into
      seminiferous tubules of normal recipient mice revealed a greater than 3-fold
      increase in SSCs compared to those from testes of non-PTU-treated donors. In
      addition, use of PTU-treated mice as recipients for transplantation of SSCs from
      normal donors revealed a greater than 3-fold increase of accessible niches
      compared to those of testes of non-PTU treated recipient mice with normal numbers
      of Sertoli cells. Importantly, the area of seminiferous tubules bordered by
      interstitial tissue and percentage of seminiferous tubules associated with blood
      vessels was found to be no different in testes of PTU-treated mice compared to
      controls, indicating that neither the vasculature nor interstitial support cell
      populations influenced the alteration of niche number. Collectively, these
      results provide direct evidence that Sertoli cells are the key somatic cell
      population dictating the number of SSCs and niches in mammalian testes.

PMID- 21084713
TI  - SERPINE2, a serine protease inhibitor extensively expressed in adult male mouse
      reproductive tissues, may serve as a murine sperm decapacitation factor.
AB  - SERPINE2, one of the potent serine protease inhibitors that modulates the
      activity of plasminogen activator and thrombin, is implicated in many biological
      processes. In the present study, we purified SERPINE2 from mouse seminal vesicle
      secretion (SVS), using liquid chromatography and identified it by liquid
      chromatography/tandem mass spectrometry, and it showed potent inhibitory activity
      against the urokinase-type plasminogen activator. SERPINE2 was expressed
      predominantly in seminal vesicles among murine male reproductive tissues. It was
      immunolocalized to the SVS and mucosal epithelium of the seminal vesicle,
      epididymis, coagulating gland, and vas deferens. In the testes, SERPINE2 was
      immunostained in spermatogonia, spermatocytes, spermatids, Leydig cells, and
      spermatozoa. SERPINE2 was also detected on the acrosomal cap of testicular and
      epididymal sperm and was suggested to be an intrinsic sperm surface protein. The
      purified SERPINE2 protein could bind to epididymal sperm. A prominent amount of
      SERPINE2 was detected on ejaculated and oviductal spermatozoa. Nevertheless,
      SERPINE2 was detected predominantly on uncapacitated sperm, indicating that
      SERPINE2 is lost before initiation of the capacitation process. Moreover,
      SERPINE2 could inhibit in vitro bovine serum albumin-induced sperm capacitation
      and prevent sperm binding to the egg, thus blocking fertilization. It acts
      through preventing cholesterol efflux, one of the initiation events of
      capacitation, from the sperm. These findings suggest that the SERPINE2 protein
      may play a role as a sperm decapacitation factor.

PMID- 21084715
TI  - Insulin-like growth factor 3 is involved in oocyte maturation in zebrafish.
AB  - The gonad-specific expression of a recently discovered Igf subtype (Igf3) in
      teleost has indicated the important role of this novel Igf in the reproductive
      functions of fish. In the present study using zebrafish as the model organism, we
      have further examined the gene expression patterns and the physiological role of
      Igf3 in the ovary. The igf3 gene in zebrafish was found to be alternatively
      spliced into two transcripts, with transcript variant 1 exclusively expressed in
      the gonads, and transcript variant 2 only expressed during early development.
      Using specific antibodies developed for zebrafish Igf3, both the Igf3
      prepropeptide and the mature peptide forms of Igf3 were found to be predominantly
      expressed in the zebrafish ovary. Real-time PCR and in situ hybridization
      revealed that igf3 mRNA is relatively low in the early follicles, but is
      significantly increased after the mid-vitellogenic stage (midstage III), and is
      high in the full-grown follicles. In the full-grown follicles, igf3 mRNA was
      detected mainly in the somatic follicular cells with a low level of expression in
      the oocytes. Igf3 immunoreactivity was confined to the follicular cells only. The
      expression of igf3 was significantly up-regulated in both ovarian fragments and
      isolated follicles upon treatment with human chorionic gonadotropin in dose- and
      time-dependent manners. Treatment with 8-bromoadenosine 3',5'-cyclic
      monophosphate or 3-isobutyl-1-methylxanthine also up-regulated the expression of
      igf3 in full-grown follicles. Incubation of follicles with recombinant zebrafish
      Igf3 significantly enhanced oocyte maturation in time-, dose-, and stage
      dependent manners. The actions of Igf3 could be blocked by cycloheximide, but not
      by actinomycin D. Taken together, these results support an important role of Igf3
      in the ovarian functions of zebrafish, especially in oocyte maturation.

PMID- 21084714
TI  - MAPK14 cooperates with MAPK3/1 to regulate endothelin-1-mediated prostaglandin
      synthase 2 induction and survival in leiomyoma but not in normal myometrial
      cells.
AB  - We recently reported that in ELT3 uterine leiomyoma cells, but not in normal
      myometrial cells, endothelin (ET)-1 exerts a survival effect insensitive to
      MAPK3/1(ERK1/2) inhibition. In the present work, we investigated the potential
      role of MAPK14 (p38) in this ET-1-mediated effect. We demonstrated that, in ELT3,
      but not in normal myometrial cells, ET-1 activated MAPK14. Data based on
      pharmacological and siRNA approaches indicate that ETA and ETB receptors
      contributed to the activation of MAPK14 by ET-1 through a mechanism involving Gi
      protein, but not PI3-kinase. The inhibition of MAPK3/1 by U0126 did not affect
      the activation of MAPK14 by ET-1. Conversely, the inhibition of MAPK14 by
      SB203580 and the down-regulation of MAP2K3/MAP2K6 (kinases upstream of MAPK14) by
      specific siRNA did not alter the activation of MAPK3/1. These data indicate that
      MAPK14 was activated by ET-1 independently from MAPK3/1. Furthermore, ET-1
      increased protein expression of prostaglandin synthase 2 (PTGS2 or COX2),
      prostaglandin E2 (PGE2) production, and subsequent ELT3 cell survival. The
      inhibition of PTGS2 induction and subsequent survival induced by ET-1 required
      the coinhibition of MAPK14 and MAPK3/1. Our findings provide evidence that ET-1
      activated MAPK14 only in ELT3 cells, but not in normal myometrial cells. This
      MAPK14 activation was required, in addition to MAPK3/1 in ET-1-mediated survival
      through the COX2/prostaglandin axis, and may explain the absence of ET-1
      antiapoptotic effect in normal myometrial cells. Our data reinforce the role of
      ET-1 and associated signaling pathways in leiomyoma pathology.

PMID- 21084716
TI  - CO2 laser improves 45S5 bioglass interaction with dentin.
AB  - Bioglass 45S5 is a bioactive glass that can create a layer of calcium-phosphate
      crystals on mineralized hard tissues. In this study, 45S5 bioglass was mixed with
      phosphoric acid and irradiated with CO(2) laser and examined as a possible aid in
      the treatment of dentin hypersensitivity. The dentinal surface modified by the
      aforementioned technique was chemically and micro-morphologically examined with a
      field emission scanning electron microscope (FE-SEM) equipped with an energy
      dispersive x-ray spectroscope (EDS), and the crystalline structures of the
      examined dentinal surfaces were examined by x-ray diffraction (XRD). Moreover,
      the mechanical properties of the newly formed layer were examined by
      nanoindentation. The results showed that 45S5 bioglass could occlude the dentinal
      tubule orifices with calcium-phosphate crystals. The application of CO(2) laser
      potentially improved the mechanical organization of these crystals.

PMID- 21084717
TI  - BEAR, a novel virtual screening methodology for drug discovery.
AB  - BEAR (binding estimation after refinement) is a new virtual screening technology
      based on the conformational refinement of docking poses through molecular
      dynamics and prediction of binding free energies using accurate scoring
      functions. Here, the authors report the results of an extensive benchmark of the
      BEAR performance in identifying a smaller subset of known inhibitors seeded in a
      large (1.5 million) database of compounds. BEAR performance proved strikingly
      better if compared with standard docking screening methods. The validations
      performed so far showed that BEAR is a reliable tool for drug discovery. It is
      fast, modular, and automated, and it can be applied to virtual screenings against
      any biological target with known structure and any database of compounds.

PMID- 21084718
TI  - News from the brain: the GPR124 orphan receptor directs brain-specific
      angiogenesis.
AB  - During development, microvessels acquire specialized functions to meet the
      requirements of different tissues and organs. The vasculature of the brain
      constitutes one of the best examples of an organ-specific and highly specialized
      microvasculature, in which the endothelial cells that line blood vessels form an
      active permeability barrier and transport system called the blood-brain barrier
      (BBB); little is known, however, about the molecular mechanisms that instruct
      endothelial cells toward a BBB phenotype. Now Kuhnert et al. reveal that the
      orphan heterotrimeric GTP-binding protein-coupled receptor GPR124/TEM5 acts as an
      organ-specific regulator of brain angiogenesis, required for normal endothelial
      cell sprouting, migration, and expression of the BBB marker Glut-1 in the
      forebrain and neural tube. These findings add to our knowledge of brain
      vascularization and may open up possibilities for new therapeutic regimes to
      treat several diseases, including stroke, brain tumors, and vascular
      malformations.

PMID- 21084719
TI  - Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of
      globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD; also known as Krabbe disease) is an invariably
      fatal lysosomal storage disorder caused by mutations in the galactocerebrosidase
      (GALC) gene. Hematopoietic stem cell (HSC)-based gene therapy is being explored
      for GLD; however, we found that forced GALC expression was toxic to HSCs and
      early progenitors, highlighting the need for improved regulation of vector
      expression. We used a genetic reporter strategy based on lentiviral vectors to
      detect microRNA activity in hematopoietic cells at single-cell resolution. We
      report that miR-126 and miR-130a were expressed in HSCs and early progenitors
      from both mice and humans, but not in differentiated progeny. Moreover,
      repopulating HSCs could be purified solely on the basis of miRNA expression,
      providing a new method relevant for human HSC isolation. By incorporating miR-126
      target sequences into a GALC-expressing vector, we suppressed GALC expression in
      HSCs while maintaining robust expression in mature hematopoietic cells. This
      approach protected HSCs from GALC toxicity and allowed successful treatment of a
      mouse GLD model, providing a rationale to explore HSC-based gene therapy for GLD.

PMID- 21084720
TI  - Femtosecond laser-assisted cataract surgery with integrated optical coherence
      tomography.
AB  - About one-third of people in the developed world will undergo cataract surgery in
      their lifetime. Although marked improvements in surgical technique have occurred
      since the development of the current approach to lens replacement in the late
      1960s and early 1970s, some critical steps of the procedure can still only be
      executed with limited precision. Current practice requires manual formation of an
      opening in the anterior lens capsule, fragmentation and evacuation of the lens
      tissue with an ultrasound probe, and implantation of a plastic intraocular lens
      into the remaining capsular bag. The size, shape, and position of the anterior
      capsular opening (one of the most critical steps in the procedure) are controlled
      by freehand pulling and tearing of the capsular tissue. Here, we report a
      technique that improves the precision and reproducibility of cataract surgery by
      performing anterior capsulotomy, lens segmentation, and corneal incisions with a
      femtosecond laser. The placement of the cuts was determined by imaging the
      anterior segment of the eye with integrated optical coherence tomography.
      Femtosecond laser produced continuous anterior capsular incisions, which were
      twice as strong and more than five times as precise in size and shape than manual
      capsulorhexis. Lens segmentation and softening simplified its emulsification and
      removal, decreasing the perceived cataract hardness by two grades. Three
      dimensional cutting of the cornea guided by diagnostic imaging creates
      multiplanar self-sealing incisions and allows exact placement of the limbal
      relaxing incisions, potentially increasing the safety and performance of cataract
      surgery.

PMID- 21084721
TI  - Qualitative analysis of therapeutic light effects on global function in
      Alzheimer's disease.
AB  - The occurrence of Alzheimer's disease (AD) is growing, with 68% of cases
      occurring in women. Declines in global function exacerbated by reversal of day
      night patterns, disturbed sleep-wake rhythms, and excessive daytime sleepiness
      make managing AD difficult. In this study, the authors examined the effect and
      duration of effect of therapeutic light on sleep, rest-activity, and global
      function in women with AD using mixed methods in a two-group experimental design
      with repeated measures on one factor. Twenty women with AD were randomized to
      experimental or control conditions. Blue-green or dim red light was delivered via
      cap visor in the morning. Results of the qualitative analysis of serial
      interviews with family and facility caregivers regarding perceived effect of
      light on global function are presented. Themes emerged in both groups with
      respect to cognition and psychosocial function. Future studies with larger
      samples using quantitative measures of global function are warranted to verify
      findings.

PMID- 21084722
TI  - Case-control study of epidemic mortality and Cardicola forsteri-associated
      disease in farmed southern bluefin tuna (Thunnus maccoyii) of South Australia.
AB  - Cardicola forsteri is a blood fluke that is highly prevalent among cultured
      southern bluefin tuna (SBT), Thunnus maccoyii, in South Australia. The role of C
      forsteri in annual SBT mortality outbreaks, which peak 6 to 12 weeks
      poststocking, is unknown. The objective of this study was to identify lesions
      unique to cultured SBT that died during a mortality event in 2009 and to
      determine the significance of C forsteri-associated lesions. Cultured SBT were
      sampled from 4 pontoons of a single site in Spencer Gulf that experienced a
      mortality epidemic that spanned 5 to 14 weeks poststocking. Study SBT comprised 7
      that died during peak mortality, 27 that did not die, and 10 wild-caught
      (noncultured) SBT. All cultured SBT had branchitis and myocarditis due to C
      forsteri, whereas no life stages of C forsteri were histologically identified in
      any wild-caught SBT. Mortality was associated with the presence of severe
      branchitis (P<.005), and the odds of severe branchitis were 90 times greater for
      SBT that died than for SBT that were live caught during peak mortality (95%
      confidence interval, 5 to 1,684). In SBT that had died, no lesions other than
      those associated with C forsteri were of sufficient severity or physiologic
      significance to account for death. Other lesions common among cultured SBT
      included systemic granulocytic perivascular infiltrate, granulocytic gastric
      infiltrate, hepatic lipidosis, visceral granulomas, and branchial parasitic
      infestation. This study shows for the first time that a substantial proportion of
      poststocking mortality in cultured SBT is strongly associated with severe
      branchitis caused by C forsteri.

PMID- 21084723
TI  - Unmet needs for home and community-based services among frail older Americans and
      their caregivers.
AB  - OBJECTIVE: This study examined unmet needs for home- and community-based services
      (HCBS) among frail older Americans. METHOD: Using population-based sample from
      the National Long-Term Care Survey, a hierarchical logistic regression analysis
      was conducted to examine the predictors of unmet needs for seven types of HCBS.
      RESULTS: Lack of awareness, reluctance, unavailability, and affordability of
      services were the main reasons for unmet needs for HCBS. Factors that were
      associated with unmet needs included Black race/ethnicity, greater care needs
      (functional limitations and behavioral problems), and less informal support
      (substitute help and family agreement). DISCUSSION: It is important to identify
      risk factors that may lead to older adults' unmet needs for HCBS. The findings of
      this study charge researchers to look beyond service utilization and give more
      attention to service needs among those who did or could not access the services.

PMID- 21084724
TI  - Illicit and nonmedical drug use among older adults: a review.
AB  - OBJECTIVE: Substance abuse among older adults is a looming public health concern.
      The number of Americans aged 50+ years with a substance use disorder is projected
      to double from 2.8 million in 2002-2006 to 5.7 million in 2020. The authors
      provide a review of epidemiological findings for this understudied area of
      research by focusing on illicit drug use disorders and nonmedical use of
      prescription drugs among adults aged 50+ years. METHOD: MEDLINE and PsychInfo
      were searched using keywords drug use, drug abuse, drug misuse, substance use
      disorder, and prescription drug abuse. Using the related-articles link,
      additional articles were screened for inclusion. This review included articles
      published between 1990 and 2010. RESULT:  RESULTS: Rates of treatment admissions
      involving primary use of illicit and misuse of prescription drugs have increased,
      while rates involving primary use of alcohol only have decreased. Alcohol,
      opioids/heroin, and cocaine were more likely than other substances to be
      associated with treatment use. Limited research data suggested the effectiveness
      of treatments, especially for women. Furthermore, older adults appeared to be
      less likely than younger adults to perceive substance use as problematic or to
      use treatment services. DISCUSSION: There is robust evidence showing that an
      increased number of older adults will need substance abuse care in the coming
      decades. Increasing demands on the substance abuse treatment system will require
      expansion of treatment facilities and development of effective service programs
      to address emerging needs of the aging drug-using population.

PMID- 21084725
TI  - Activation of mitochondrial energy metabolism protects against cardiac failure.
AB  - Cardiac failure is the most prevalent cause of death at higher age, and is
      commonly associated with impaired energy homeostasis in the heart. Mitochondrial
      metabolism appears critical to sustain cardiac function to counteract aging. In
      this study, we generated mice transgenically over-expressing the mitochondrial
      protein frataxin, which promotes mitochondrial energy conversion by controlling
      iron-sulfur-cluster biogenesis and hereby mitochondrial electron flux. Hearts of
      transgenic mice displayed increased mitochondrial energy metabolism and induced
      stress defense mechanisms, while overall oxidative stress was decreased.
      Following standardized exposure to doxorubicin to induce experimental
      cardiomyopathy, cardiac function and survival was significantly improved in the
      transgenic mice. The insulin/IGF-1 signaling cascade is an important pathway that
      regulates survival following cytotoxic stress through the downstream targets
      protein kinase B, Akt, and glycogen synthase kinase 3. Activation of this cascade
      is markedly inhibited in the hearts of wild-type mice following induction of
      cardiomyopathy. By contrast, transgenic overexpression of frataxin rescues
      impaired insulin/IGF-1 signaling and provides a mechanism to explain enhanced
      cardiac stress resistance in transgenic mice. Taken together, these findings
      suggest that increased mitochondrial metabolism elicits an adaptive response due
      to mildly increased oxidative stress as a consequence of increased oxidative
      energy conversion, previously named mitohormesis. This in turn activates
      protective mechanisms which counteract cardiotoxic stress and promote survival in
      states of experimental cardiomyopathy. Thus, induction of mitochondrial
      metabolism may be considered part of a generally protective mechanism to prevent
      cardiomyopathy and cardiac failure.

PMID- 21084726
TI  - MKK4 as oncogene or tumor suppressor: in cancer and senescence, the story's
      getting old.

PMID- 21084727
TI  - A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3
      addiction.
AB  - The pro-oncogenic transcription factor STAT3 is constitutively activated in a
      wide variety of tumours that often become addicted to its activity, but no
      unifying view of a core function determining this widespread STAT3-dependence has
      yet emerged. We show here that constitutively active STAT3 acts as a master
      regulator of cell metabolism, inducing aerobic glycolysis and down-regulating
      mitochondrial activity both in primary fibroblasts and in STAT3-dependent tumour
      cell lines. As a result, cells are protected from apoptosis and senescence while
      becoming highly sensitive to glucose deprivation. We show that enhanced
      glycolysis is dependent on HIF-1alpha up-regulation, while reduced mitochondrial
      activity is HIF-1alpha-independent and likely caused by STAT3-mediated down
      regulation of mitochondrial proteins. The induction of aerobic glycolysis is an
      important component of STAT3 pro-oncogenic activities, since inhibition of STAT3
      tyrosine phosphorylation in the tumour cell lines down-regulates glycolysis prior
      to leading to growth arrest and cell death, both in vitro and in vivo. We propose
      that this novel, central metabolic role is at the core of the addiction for STAT3
      shown by so many biologically different tumours.

PMID- 21084728
TI  - A novel insight into aging: are there pluripotent very small embryonic-like stem
      cells (VSELs) in adult tissues overtime depleted in an Igf-1-dependent manner?
AB  - Tissue and organ rejuvenation and senescence/aging are closely related to the
      function of stem cells. Recently, we demonstrated that a population of
      pluripotent Oct-4+ SSEA-1+Sca-1+Lin-CD45- very small embryonic-like stem cells
      (VSELs) resides in the adult murine bone marrow (BM) and other murine tissues. We
      hypothesize that these pluripotent stem cells play an important role in
      tissue/organ rejuvenation, and have demonstrated that their proliferation and
      potentially premature depletion is negatively controlled by epigenetic changes of
      some imprinted genes that regulate insulin factor signaling (Igf2-H19 locus,
      Igf2R and RasGRF1). Since the attenuation of insulin/insulin growth factor
      (Ins/Igf) signaling positively correlates with longevity, we propose, based on
      our experimental data, that gradual decrease in the number of VSELs deposited in
      adult tissues, which occurs throughout life in an Ins/Igf signaling-dependent
      manner is an important mechanism of aging. In contrast, a decrease in Ins/Igf
      stimulation of VSELs that extends the half life of these cells in adult organs
      would have a beneficial effect on life span. Our preliminary data in long-living
      Igf-1-signaling-deficient mice show that these animals possess a 3-4 times higher
      number of VSELs deposited in adult BM, lending support to this novel hypothesis.

PMID- 21084730
TI  - Modeling deep brain stimulation: point source approximation versus realistic
      representation of the electrode.
AB  - Deep brain stimulation (DBS) has emerged as an effective treatment for movement
      disorders; however, the fundamental mechanisms by which DBS works are not well
      understood. Computational models of DBS can provide insights into these
      fundamental mechanisms and typically require two steps: calculation of the
      electrical potentials generated by DBS and, subsequently, determination of the
      effects of the extracellular potentials on neurons. The objective of this study
      was to assess the validity of using a point source electrode to approximate the
      DBS electrode when calculating the thresholds and spatial distribution of
      activation of a surrounding population of model neurons in response to monopolar
      DBS. Extracellular potentials in a homogenous isotropic volume conductor were
      calculated using either a point current source or a geometrically accurate finite
      element model of the Medtronic DBS 3389 lead. These extracellular potentials were
      coupled to populations of model axons, and thresholds and spatial distributions
      were determined for different electrode geometries and axon orientations. Median
      threshold differences between DBS and point source electrodes for individual
      axons varied between -20.5% and 9.5% across all orientations, monopolar
      polarities and electrode geometries utilizing the DBS 3389 electrode. Differences
      in the percentage of axons activated at a given amplitude by the point source
      electrode and the DBS electrode were between -9.0% and 12.6% across all monopolar
      configurations tested. The differences in activation between the DBS and point
      source electrodes occurred primarily in regions close to conductor-insulator
      interfaces and around the insulating tip of the DBS electrode. The robustness of
      the point source approximation in modeling several special cases--tissue
      anisotropy, a long active electrode and bipolar stimulation--was also examined.
      Under the conditions considered, the point source was shown to be a valid
      approximation for predicting excitation of populations of neurons in response to
      DBS.

PMID- 21084731
TI  - Designing a somatosensory neural prosthesis: percepts evoked by different
      patterns of thalamic stimulation.
AB  - Although major advances have been made in the development of motor prostheses,
      fine motor control requires intuitive somatosensory feedback. Here we explored
      whether a thalamic site for a somatosensory neural prosthetic could provide
      natural somatic sensation to humans. Different patterns of electrical stimulation
      (obtained from thalamic spike trains) were applied in patients undergoing deep
      brain stimulation surgery. Changes in pattern produced different sensations,
      while preserving somatotopic representation. While most percepts were reported as
      'unnatural', some stimulations produced more 'natural' sensations than others.
      However, the additional patterns did not elicit more 'natural' percepts than high
      frequency (333 Hz) electrical stimulation. These features suggest that despite
      some limitations, the thalamus may be a feasible site for a somatosensory neural
      prosthesis and different stimulation patterns may be useful in its development.

PMID- 21084729
TI  - Metformin for aging and cancer prevention.
AB  - Studies in mammals have led to the suggestion that hyperglycemia and
      hyperinsulinemia are important factors in aging. Insulin/insulin-like growth
      factor 1 (IGF-1) signaling molecules that have been linked to longevity include
      daf-2 and InR and their homologues in mammals, and inactivation of the
      corresponding genes increases life span in nematodes, fruit flies and mice. It is
      possible that the life-prolonging effect of caloric restriction is due to
      decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are
      promising candidates for both life span extension and prevention of cancer. Thus,
      antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well
      as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore
      metformin seems to decrease cancer risk in diabetic patients.

PMID- 21084732
TI  - Evaluation of novel stimulus waveforms for deep brain stimulation.
AB  - Deep brain stimulation (DBS) is an established therapy for the treatment of a
      wide range of neurological disorders. Historically, DBS and other
      neurostimulation technologies have relied on rectangular stimulation waveforms to
      impose their effects on the nervous system. Recent work has suggested that non
      rectangular waveforms may have advantages over the traditional rectangular pulse.
      Therefore, we used detailed computer models to compare a range of charge-balanced
      biphasic waveforms with rectangular, exponential, triangular, Gaussian and
      sinusoidal stimulus pulse shapes. We explored the neural activation energy of
      these waveforms for both intracellular and extracellular current-controlled
      stimulation conditions. In the context of extracellular stimulation, we compared
      their effects on both axonal fibers of passage and projection neurons. Finally,
      we evaluated the impact of delivering the waveforms through a clinical DBS
      electrode, as opposed to a theoretical point source. Our results suggest that DBS
      with a 1 ms centered-triangular pulse can decrease energy consumption by 64% when
      compared with the standard 100 us rectangular pulse (energy cost of 48 and 133
      nJ, respectively, to stimulate 50% of a distributed population of axons) and can
      decrease energy consumption by 10% when compared with the most energy efficient
      rectangular pulse (1.25 ms duration). In turn, there may be measureable energy
      savings when using appropriately designed non-rectangular pulses in clinical DBS
      applications, thereby warranting further experimental investigation.

PMID- 21084733
TI  - Cerebrospinal fluid markers for Alzheimer's disease over the lifespan: effects of
      age and the APOEepsilon4 genotype.
AB  - In Alzheimer's disease (AD), the cerebral pathological changes begin many years
      before the clinical manifestation of the disease. Biomarkers for AD, such as the
      cerebrospinal fluid (CSF) concentrations of amyloid-beta1-42 (Abeta1-42) and tau
      phosphorylated at threonine 181 (pTau181), may reflect these cerebral changes
      relatively early. Accordingly, cognitively healthy subjects at risk for AD often
      have altered CSF concentrations of Abeta1-42 and pTau181. In this study, we
      assessed the effects and interaction of two strong risk factors for AD, aging and
      the presence of the APOEepsilon4 allele, on the CSF Abeta1-42 and pTau181
      concentrations in 280 adults with normal cognition across the lifespan. For
      comparison, we further included 152 patients with probable AD. We found
      significant effects of age on the CSF Abeta1-42 and pTau181, and of the
      APOEepsilon4 genotype on the Abeta1-42 levels in the cognitively normal
      participants. Carrying the APOEepsilon4 allele was associated with a significant
      decrease of the Abeta1-42 concentrations in middle-aged and older participants.
      In the group of participants with AD, the Abeta1-42 levels were significantly
      lower in the APOEepsilon4 carriers compared to the non-carriers. These findings
      demonstrate significant age effects on the CSF Abeta1-42 and pTau181 across
      lifespan. They also suggest that the decrease of Abeta1-42, but not the increase
      of pTau181 CSF levels is accelerated by the APOEepsilon4 genotype in middle-aged
      and older adults with normal cognition.

PMID- 21084736
TI  - Two- and three-dimensional accuracy of dental impression materials: effects of
      storage time and moisture contamination.
AB  - Dental impression materials are used to create an inverse replica of the dental
      hard and soft tissues, and are used in processes such as the fabrication of
      crowns and bridges. The accuracy and dimensional stability of impression
      materials are of paramount importance to the accuracy of fit of the resultant
      prosthesis. Conventional methods for assessing the dimensional stability of
      impression materials are two-dimensional (2D), and assess shrinkage or expansion
      between selected fixed points on the impression. In this study, dimensional
      changes in four impression materials were assessed using an established 2D and an
      experimental three-dimensional (3D) technique. The former involved measurement of
      the distance between reference points on the impression; the latter a contact
      scanning method for producing a computer map of the impression surface showing
      localised expansion, contraction and warpage. Dimensional changes were assessed
      as a function of storage times and moisture contamination comparable to that
      found in clinical situations. It was evident that dimensional changes observed
      using the 3D technique were not always apparent using the 2D technique, and that
      the former offers certain advantages in terms of assessing dimensional accuracy
      and predictability of impression methods. There are, however, drawbacks
      associated with 3D techniques such as the more time-consuming nature of the data
      acquisition and difficulty in statistically analysing the data.

PMID- 21084737
TI  - Finite element analysis of the scoliotic spine under different loading
      conditions.
AB  - The role of the vertebral body's rotation and the loading conditions of the brace
      has not been clearly identified in adolescent idiopathic scoliosis. This study
      aimed to implement a finite element (FE) model of C-type scoliotic spines to
      investigate the influence of different loading conditions on variations of Cobb's
      angle and the vertebral rotation. The scoliotic FE model was constructed from C7
      to L5, and its geometry was the right thoracic type (37.4 degrees ) with an apex
      over T7. Three loading conditions included a medial-lateral (ML) and
      anteroposterior (AP) force with a magnitudes of 100-0, 80-20 and 60-40 N. Those
      forces were respectively applied over the 6th, 7th and 8th ribs. According to an
      analysis of Cobb's angle, the 100 N ML force that was applied over the 8th rib
      could achieve the best correction effect. Furthermore, the ML force was dominant
      in alterations of Cobb's angle, whereas the AP force was dominant in alterations
      of the axial vertebral rotation. Additionally, the level below the apex was the
      most appropriate level to apply the force to correct C-type scoliosis.

PMID- 21084738
TI  - Application of artificial tactile sensing approach in kidney-stone-removal
      laparoscopy.
AB  - Artificial tactile sensing is a novel method for obtaining different
      characteristics of a hard object embedded in a soft tissue. In this regard,
      artificial palpation is one of the most valuable achievements of artificial
      tactile sensing that can be used in various fields of medicine and more
      specifically in surgery. In this study, considering the present problems and
      limitations in kidney-stone-removal laparoscopy, a new application will be
      presented for artificial tactile sensing approach. Having imitated surgeon's
      palpation during open surgery and modeled it conceptually, indications of stone
      existence that appear on the surface of kidney (due to exerting mechanical load)
      were determined. A number of different cases were created and solved by the
      software. Using stress distribution contours and stress graphs, it is illustrated
      that the created stress patterns on the surface of kidney not only show the
      existence of stone inside, but also its exact location. In fact, the reliability
      and accuracy of artificial tactile sensing method in detection of kidney stone
      during laparoscopy is demonstrated by means of finite element analysis. Also, in
      this paper, the functional principles of tactile system capable of determining
      the exact location of stone during laparoscopy will be presented.

PMID- 21084739
TI  - Degradative-release as a function of drug structure from LDI-glycerol
      polyurethanes.
AB  - Naphthalene analogs with differing hydroxyl and amine functionality were
      incorporated into degradable polyurethane foams synthesized from lysine
      diisocyanate and glycerol to determine if chemical structure can be used in
      controlled release systems. Excitation and emission spectra of the various
      naphthalene analogs in aqueous solution were collected to ensure they were
      capable of being quantitatively detected in aqueous solution at low
      concentrations. The fluorescence stability of the compounds was assessed over a 2
      week period at 70 degrees C; the analogs were all found to exhibit signal decay
      to varying degrees. Polyurethane foam materials containing the naphthalene
      analogs were synthesized and examined via scanning electron microscopy;
      incorporating naphthalene ligands did not grossly alter the polyurethane
      morphology. The analog distribution was then assessed via fluorescence
      microscopy, and the naphthalene analogs were found evenly dispersed throughout
      the polyurethane materials. Foam samples containing various analogs were then
      incubated in PBS buffer solution (pH 7.4) at 4, 22, 37 and 70 degrees C for 11
      weeks. Temperature dependent release of naphthalene analogs from the polyurethane
      foams was found to depend upon the functional groups present on the naphthalene
      analog. These results suggest that the chemical structure of a drug plays a
      unique role in controlling release from hydrolytically degradable drug delivery
      systems.

PMID- 21084740
TI  - Polishing of dental porcelain by polycrystalline diamond.
AB  - Polycrystalline diamond (PCD) exhibits excellent abrasive characteristics and is
      commonly used as loose grains for precision machining of hard ceramics and other
      materials that are difficult to grind and polish. In the present study, we
      investigated using bonded PCD for polishing dental porcelain, for which a
      lustrous surface is difficult to obtain by polishing. We compared the surface
      texture and characteristics of dental porcelain after polishing with bonded PCD
      with that obtained using bonded monocrystalline diamond (MCD), which is commonly
      used for this purpose. Polishing was performed at various pressures and
      rotational speeds on a custom-built polishing apparatus using bonded PCD or MCD
      with grain sizes of 3.92 MUm on specimens consisting of VITA Omega 900 dentin
      porcelain after firing and then glazing to a specified surface roughness. The
      surface roughness of the polished porcelain and the abrasion quantity in terms of
      its polishing depth were measured, and its surface texture and characteristics
      were investigated. At low polishing pressures, PCD yielded a finer polished
      surface than MCD. The polishing depth after polishing for 20-30 min was
      approximately 2-3 MUm with PCD and 1-2 MUm with MCD. The polished surface was
      more uniform and smooth with PCD than with MCD.

PMID- 21084741
TI  - Promoted dermis healing from full-thickness skin defect by porous silk fibroin
      scaffolds (PSFSs).
AB  - Studies on skin substitutes and dermal scaffolds have been extensively carried
      out in the past several decades and some commercial products derived from
      collagen and polymers have been in marketing. Yet little research on silk fibroin
      based dermal scaffolds and products has been reported so far. In the present
      study, therefore, porous silk fibroin scaffolds (PSFSs) have been prepared by
      freeze drying method. The effects of PSFSs on skin recovery from full thickness
      defect have been examined by histological evaluation with respect to
      neovascularization, dermal regeneration and infiltration of inflammatory cells.
      In addition, tissue compatibility between PSFSs and polyvinyl alcohol (PVA)
      sponges (as control) has been semiquantitatively compared by scoring method. The
      results showed that at day 18 after implantation, new tissues formed in PSFSs
      whose structure was almost equal to normal skin structure where proportional
      distribution of functional blood vessels could be found. Furthermore,
      infiltration of inflammatory cells in PSFSs disappeared within 7 days. By
      contrast, a variety of interstices, fibrous encapsulization and moderate
      infiltration of inflammatory cells could be found in PVA sponges at day 18 after
      implantation. In summary, PSFSs has significantly promoted the skin recovery from
      full thickness defect, showing fibroin's outstanding tissue compatibility.

PMID- 21084742
TI  - Cell morphological response to low shear stress in a two-dimensional culture
      microsystem with magnitudes comparable to interstitial shear stress.
AB  - Slow interstitial flow can lead to large changes in cell morphology. Since
      conventional biological assays are adapted to two-dimensional culture protocols,
      there is a need to develop a microfluidic system that can generate physiological
      levels of interstitial flow. Here we developed a system that uses a passive
      osmotic pumping mechanism to generate sustained and steady interstitial flows for
      two-dimensional cultures. Two different cell types, fibroblasts and mesenchymal
      stem cells, were selected because they are generally exposed to interstitial
      flow. To quantify the cellular response to interstitial shear flow in terms of
      proliferation and alignment, 4 rates of flow were applied. We found that the
      proliferation rate of fibroblasts varied linearly with wall shear stress. In
      addition, alignment of fibroblast cells depended linearly on the magnitude of the
      shear stress, whereas mesenchymal stem cells were aligned regardless of the
      magnitude of shear stress. This suggested that mesenchymal stem cells are very
      sensitive to shear stresses, even at levels generated by interstitial flow. The
      results presented here emphasize the need to consider the mechanosensitivity and
      the natural role of different cell types when evaluating their responses to fluid
      flow.

PMID- 21084743
TI  - Shear stress induces a transient and VEGFR-2-dependent decrease in the motion of
      injected particles in endothelial cells.
AB  - Vascular endothelial cells form the inner lining of all blood vessels and play a
      central role in vessel physiology and disease. Endothelial cells are highly
      responsive to the mechanical stimulus of fluid shear stress that is exerted by
      blood flowing over their surface. In this study, the immediate micromechanical
      response of endothelial cells to physiological shear stress was characterized by
      tracking of ballistically injected, sub-micron, fluorescent particles. It was
      found that the mean squared displacement (MSD) of the particles decreases by a
      factor 1.5 within 10 min after the onset of shear stress. This decrease in
      particle motion is transient, since the MSD returns to control values within 15
      30 min after the onset of shear. The immediate micromechanical stiffening is
      dependent on activation of the vascular endothelial growth factor receptor
      (VEGFR)-2, because inhibition of the receptor abrogates the micromechanical
      response. This work shows that the cytoskeleton is actively involved in the
      acute, functional response of endothelial cells to shear stress.

PMID- 21084744
TI  - Drag-reducing polymers diminish near-wall concentration of platelets in
      microchannel blood flow.
AB  - The accumulation of platelets near the blood vessel wall or artificial surface is
      an important factor in the cascade of events responsible for coagulation and/or
      thrombosis. In small blood vessels and flow channels this phenomenon has been
      attributed to the blood phase separation that creates a red blood cell (RBC)-poor
      layer near the wall. We hypothesized that blood soluble drag-reducing polymers
      (DRP), which were previously shown to lessen the near-wall RBC depletion layer in
      small channels, may consequently reduce the near-wall platelet excess. This study
      investigated the effects of DRP on the lateral distribution of platelet-sized
      fluorescent particles (diam. = 2 MUm, 2.5 * 108/ml) in a glass square
      microchannel (width and depth = 100 MUm). RBC suspensions in PBS were mixed with
      particles and driven through the microchannel at flow rates of 6-18 ml/h with and
      without added DRP (10 ppm of PEO, MW = 4500 kDa). Microscopic flow visualization
      revealed an elevated concentration of particles in the near-wall region for the
      control samples at all tested flow rates (between 2.4 +/- 0.8 times at 6 ml/h and
      3.3 +/- 0.3 times at 18 ml/h). The addition of a minute concentration of DRP
      virtually eliminated the near-wall particle excess, effectively resulting in
      their even distribution across the channel, suggesting a potentially significant
      role of DRP in managing and mitigating thrombosis.

PMID- 21084745
TI  - Characterization and comparison of shear and extensional flow of sodium
      hyaluronate and human synovial fluid.
AB  - The focus of this work is on a comparative rheological characterization of sodium
      hyaluronate (NaHA) samples from fermentative production (NaHA-1, Mw = 1.7 * 106
      g/mol) and from rooster comb (NaHA-2, Mw = 4.6 * 106 g/mol) with synovial fluid
      (SF) taken post mortem from different patients above 60 years. Steady state shear
      flow and uniaxial extension experiments were carried out for different
      concentrations of NaHA in 0.01 M phosphate-buffered saline (PBS) and on several
      SF samples.The synovial fluid of older patients was found to have a
      viscoelasticity comparable to that of younger patients investigated in earlier
      studies. Comparison of steady state shear experiments revealed a comparable
      progression for the viscosity curves of NaHA-2 and SF. This behavior was also
      observed in extensional flow, where comparable results for NaHA-2 and different
      SF samples were obtained.

PMID- 21084746
TI  - Cardiac mechanoenergetic cost of elevated plasma viscosity after moderate
      hemodilution.
AB  - The purpose of this study was to investigate how plasma viscosity affects cardiac
      and vascular function during moderate hemodilution. Twelve anesthetized hamsters
      were hemodiluted by 40% of blood volume with two different viscosity plasma
      expanders. Experimental groups were based on the plasma expander viscosity,
      namely: high viscosity plasma expander (HVPE, 6.3 mPa . s) and low viscosity
      plasma expander (LVPE, 2.2 mPa . s). Left ventricular (LV) function was
      intracardiacally measured with a high temporal resolution miniaturized
      conductance catheter and concurrent pressure-volume results were used to
      calculate different LV indices. Independently of the plasma expander,
      hemodilution decreased hematocrit to 28% in both groups. LVPE hemodilution
      reduced whole blood viscosity by 40% without changing plasma viscosity, while
      HVPE hemodilution reduced whole blood viscosity by 23% and almost doubled plasma
      viscosity relative to baseline. High viscosity plasma expander hemodilution
      significantly increased cardiac output, stroke volume and stroke work compared to
      baseline, whereas LVPE hemodilution did not. Furthermore, an increase in plasma
      viscosity during moderate hemodilution produced a higher energy transfer per unit
      volume of ejected blood. Systemic vascular resistance decreased after
      hemodilution in both groups. Counter-intuitively, HVPE hemodilution showed lower
      vascular resistance and vascular hindrance than LVPE hemodilution. This result
      suggests that geometrical changes in the circulatory system are induced by the
      increase in plasma viscosity. In conclusion, an increase in plasma viscosity
      after moderate hemodilution directly influenced cardiac and vascular function by
      maintaining hydraulic power and reducing systemic vascular resistance through
      vasodilation.

PMID- 21084747
TI  - Evaluation of the function of arteriolar opening by variability in
      microcirculatory blood flow following angiotensin II administration in rats.
AB  - OBJECTIVE: We aimed to verify whether microcirculatory blood flow variability
      (MBFV) parameters calculated from beat-to-beat laser Doppler flowmetry (LDF)
      waveforms can be used instead of microcirculatory blood flow (MBF) as an index to
      discriminate different local microcirculatory regulation in terms of the opening
      condition of arteriolar openings (AO) at different sites. METHODS: Angiotensin II
      (Ang-II) was administered to nine healthy male rats. LDF probes were placed on
      their renal cortex and plantar palm. The pulse width (PW) and coefficient of
      variance of the flux (phi) for all the pulses within a data sequence was
      calculated to evaluate the AO's opening condition. RESULTS: Monitoring and
      prediction linear-regression analyses revealed significant positive phi-vs-MU
      (mean flux) and PW-vs-MU slopes at renal cortex for their changes relative to the
      baseline values. CONCLUSION: The present results suggest that these parameters
      calculated from the beat-to-beat LDF waveform could be useful for monitoring MBF
      by administering Ang-II. Moreover, possible time-domain causal relation between
      changes in MU and these parameters was revealed, which may allow the prediction
      of changes in MBF that occur 10-30 min thereafter. Deeper understanding of MBFV
      parameters could be useful in monitoring of progression of cardiovascular
      diseases and in predicting the efficacy of specific therapies.

PMID- 21084748
TI  - Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to
      a multisystem selenoprotein deficiency disorder in humans.
AB  - Selenium, a trace element that is fundamental to human health, is incorporated
      into some proteins as selenocysteine (Sec), generating a family of
      selenoproteins. Sec incorporation is mediated by a multiprotein complex that
      includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2).
      Here, we describe subjects with compound heterozygous defects in the SECISBP2
      gene. These individuals have reduced synthesis of most of the 25 known human
      selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of
      the latter stages of spermatogenesis, was associated with a lack of testis
      enriched selenoproteins. An axial muscular dystrophy was also present, with
      features similar to myopathies caused by mutations in selenoprotein N (SEPN1).
      Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and
      susceptibility to ultraviolet radiation-induced oxidative damage may mediate the
      observed photosensitivity. Reduced levels of selenoproteins in peripheral blood
      cells were associated with impaired T lymphocyte proliferation, abnormal
      mononuclear cell cytokine secretion, and telomere shortening. Paradoxically,
      raised ROS in affected subjects was associated with enhanced systemic and
      cellular insulin sensitivity, similar to findings in mice lacking the antioxidant
      selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is
      associated with a multisystem disorder with defective biosynthesis of many
      selenoproteins, highlighting their role in diverse biological processes.

PMID- 21084749
TI  - Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral
      persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity.
AB  - Having successfully developed mechanisms to evade immune clearance, hepatitis C
      virus (HCV) establishes persistent infection in approximately 75%-80% of
      patients. In these individuals, the function of HCV-specific CD8+ T cells is
      impaired by ligation of inhibitory receptors, the repertoire of which has
      expanded considerably in the past few years. We hypothesized that the
      coexpression of the negative regulatory receptors T cell immunoglobulin and mucin
      domain-containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV
      infection would identify patients at risk of developing viral persistence during
      and after acute HCV infection. The frequency of PD-1-Tim-3- HCV-specific CTLs
      greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection.
      Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the
      central memory T cell subset and within the liver. Blockade of either PD-1 or Tim
      3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent,
      whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV
      epitopes was increased exclusively by Tim-3 blockade. These results indicate that
      the coexpression of these inhibitory molecules tracks with defective T cell
      responses and that anatomical differences might account for lack of immune
      control of persistent pathogens, which suggests their manipulation may represent
      a rational target for novel immunotherapeutic approaches.

PMID- 21084750
TI  - Transplantation of mouse HSCs genetically modified to express a CD4-restricted
      TCR results in long-term immunity that destroys tumors and initiates spontaneous
      autoimmunity.
AB  - The development of effective cancer immunotherapies has been consistently
      hampered by several factors, including an inability to instigate long-term
      effective functional antitumor immunity. This is particularly true for
      immunotherapies that focus on the adoptive transfer of activated or genetically
      modified mature CD8+ T cells. In this study, we sought to alter and enhance long
      term host immunity by genetically modifying, then transplanting, mouse HSCs. We
      first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4+ TCR
      specific for the melanocyte differentiation antigen tyrosinase-related protein 1
      (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR
      transgenic mouse expressing the genes encoding this TCR. Using these tools, we
      demonstrated that both mouse and human HSCs established durable, high-efficiency
      TCR gene transfer following long-term transplantation into lethally irradiated
      mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs
      developed spontaneous autoimmune vitiligo that was associated with the presence
      of a Th1-polarized memory effector CD4+ T cell population that expressed the
      Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing
      the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant
      recipients, and these mice were able to destroy subcutaneously administered
      melanoma cells without the aid of vaccination, immune modulation, or cytokine
      administration. These results demonstrate the creation of what we believe to be a
      novel translational model of durable lentiviral gene transfer that results in
      long-term effective immunity.

PMID- 21084751
TI  - Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to
      the prevention of ChREBP-dependent hepatic steatosis in mice.
AB  - Obesity and type 2 diabetes are associated with increased lipogenesis in the
      liver. This results in fat accumulation in hepatocytes, a condition known as
      hepatic steatosis, which is a form of nonalcoholic fatty liver disease (NAFLD),
      the most common cause of liver dysfunction in the United States. Carbohydrate
      responsive element-binding protein (ChREBP), a transcriptional activator of
      glycolytic and lipogenic genes, has emerged as a major player in the development
      of hepatic steatosis in mice. However, the molecular mechanisms enhancing its
      transcriptional activity remain largely unknown. In this study, we have
      identified the histone acetyltransferase (HAT) coactivator p300 and
      serine/threonine kinase salt-inducible kinase 2 (SIK2) as key upstream regulators
      of ChREBP activity. In cultured mouse hepatocytes, we showed that glucose
      activated p300 acetylated ChREBP on Lys672 and increased its transcriptional
      activity by enhancing its recruitment to its target gene promoters. SIK2
      inhibited p300 HAT activity by direct phosphorylation on Ser89, which in turn
      decreased ChREBP-mediated lipogenesis in hepatocytes and mice overexpressing
      SIK2. Moreover, both liver-specific SIK2 knockdown and p300 overexpression
      resulted in hepatic steatosis, insulin resistance, and inflammation, phenotypes
      reversed by SIK2/p300 co-overexpression. Finally, in mouse models of type 2
      diabetes and obesity, low SIK2 activity was associated with increased p300 HAT
      activity, ChREBP hyperacetylation, and hepatic steatosis. Our findings suggest
      that inhibition of hepatic p300 activity may be beneficial for treating hepatic
      steatosis in obesity and type 2 diabetes and identify SIK2 activators and
      specific p300 inhibitors as potential targets for pharmaceutical intervention.

PMID- 21084752
TI  - Trib1 is a lipid- and myocardial infarction-associated gene that regulates
      hepatic lipogenesis and VLDL production in mice.
AB  - Recent genome-wide association studies have identified a genetic locus at human
      chromosome 8q24 as having minor alleles associated with lower levels of plasma
      triglyceride (TG) and LDL cholesterol (LDL-C), higher levels of HDL-C, as well as
      decreased risk for myocardial infarction. This locus contains only one annotated
      gene, tribbles homolog 1 (TRIB1), which has not previously been implicated in
      lipoprotein metabolism. Here we demonstrate a role for Trib1 as a regulator of
      lipoprotein metabolism in mice. Hepatic-specific overexpression of Trib1 reduced
      levels of plasma TG and cholesterol by reducing VLDL production; conversely,
      Trib1-knockout mice showed elevated levels of plasma TG and cholesterol due to
      increased VLDL production. Hepatic Trib1 expression was inversely associated with
      the expression of key lipogenic genes and measures of lipogenesis. Thus, we
      provide functional evidence for what we believe to be a novel gene regulating
      hepatic lipogenesis and VLDL production in mice that influences plasma lipids and
      risk for myocardial infarction in humans.

PMID- 21084753
TI  - The proteoglycan biglycan regulates expression of the B cell chemoattractant
      CXCL13 and aggravates murine lupus nephritis.
AB  - CXCL13 is a key B cell chemoattractant and marker of disease activity in patients
      with SLE; however, the mechanism of its induction has not been identified yet.
      Here, we have shown that the proteoglycan biglycan triggers CXCL13 expression via
      TLR2/4 in macrophages and dendritic cells. In vivo, levels of biglycan were
      markedly elevated in the plasma and kidneys of human SLE patients and lupus-prone
      (MRL/lpr) mice. Overexpression of soluble biglycan in MRL/lpr mice raised plasma
      and renal levels of CXCL13 and caused accumulation of B cells with an enhanced
      B1/B cell ratio in the kidney, worsening of organ damage, and albuminuria.
      Importantly, biglycan also triggered CXCL13 expression and B cell infiltration in
      the healthy kidney. Conversely, biglycan deficiency improved systemic and renal
      outcome in lupus-prone mice, with lower levels of autoantibodies, less
      enlargement of the spleen and lymph nodes, and reduction in renal damage and
      albuminuria. This correlated with a marked decline in circulating and renal
      CXCL13 and a reduction in the number of B cells in the kidney. Collectively, our
      results describe what we believe to be a novel mechanism for the regulation of
      CXCL13 by biglycan, a host-derived ligand for TLR2/4. Blocking biglycan-TLR2/4
      interactions might be a promising strategy for the management of SLE and other B
      cell-mediated inflammatory disease entities.

PMID- 21084754
TI  - Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs.
AB  - In individuals with type 1 diabetes, hypoglycemia is a common consequence of
      overinsulinization. Under conditions of insulin-induced hypoglycemia, glucagon is
      the most important stimulus for hepatic glucose production. In contrast, during
      euglycemia, insulin potently inhibits glucagon's effect on the liver. The first
      aim of the present study was to determine whether low blood sugar augments
      glucagon's ability to increase glucose production. Using a conscious catheterized
      dog model, we found that hypoglycemia increased glucagon's ability to overcome
      the inhibitory effect of insulin on hepatic glucose production by almost 3-fold,
      an effect exclusively attributable to marked enhancement of the effect of
      glucagon on net glycogen breakdown. To investigate the molecular mechanism by
      which this effect comes about, we analyzed hepatic biopsies from the same
      animals, and found that hypoglycemia resulted in a decrease in insulin signaling.
      Furthermore, hypoglycemia and glucagon had an additive effect on the activation
      of AMPK, which was associated with altered activity of the enzymes of glycogen
      metabolism.

PMID- 21084755
TI  - Off-pump coronary artery bypass vs percutaneous coronary intervention.
      Therapeutic strategies for 3-vessel coronary artery disease: OPCAB vs PCI(PCI
      Side).
AB  - Coronary artery bypass graft (CABG) surgery is still the best therapy for
      patients with multivessel and left main coronary artery disease. Recently, the
      introduction of percutaneous coronary intervention (PCI) with drug-eluting stents
      (DES) in these patients has improved the restenosis rate compared with bare metal
      stents. Furthermore, according to the results of the SYNTAX trial, no differences
      were found in the frequencies of mortality or myocardial infarction between CABG
      and PCI patients. PCI with DES is being increasingly performed for the treatment
      of patients with either left main trunk, diffuse, or multivessel lesions. In
      Japan, to avoid any side effects from cardiopulmonary bypass, off-pump coronary
      artery bypass (OPCAB) was performed in 66% of the total isolated CABG procedures
      in 2009, and is markedly different from the procedures performed in North America
      and Europe. However, the comparative effectiveness of PCI and OPCAB remains
      uncertain. In the present study, the current evidence from randomized trials, a
      meta-analysis and several observation studies are reviewed.

PMID- 21084756
TI  - Is angioplasty able to become the gold standard of treatment beyond bypass
      surgery for patients with multivessel coronary artery disease? Therapeutic
      strategies for 3-vessel coronary artery disease: OPCAB vs PCI(PCI-Side).
AB  - This article reviews the treatment of patients with multivessel coronary artery
      disease (CAD). Percutaneous coronary intervention (PCI) has been challenging
      coronary artery bypass grafting (CABG) as the gold standard of care for patients
      with multivessel disease; however, the application of PCI to these patients has
      been mainly limited by restenosis. Up to the beginning of the 2000s, many large
      scale, randomized trials addressed this issue by comparing CABG to PCI with
      balloon angioplasty or bare metal stents in not only Western countries but also
      in Asian countries. These studies demonstrated similar rates of all-cause death
      and myocardial infarction in both groups, although the need for revascularization
      remained significantly lower in the CABG group. PCI with drug-eluting stents
      (DES) is safe and may represent a viable alternative to CABG for selected
      patients with diabetes and multivessel CAD. Moreover, DES implantation under
      intravascular ultrasound guidance and with fractional flow reserve might have the
      potential to influence treatment strategy and reduce both DES thrombosis and
      repeat revascularization. The evolution of DES and advanced vascular imaging
      would mean that PCI continues to challenge CABG as treatment of choice for
      patients who need revascularization for a better prognosis.

PMID- 21084758
TI  - Role of cellular senescence in lifestyle-related disease.
AB  - Epidemiological studies have shown that age is the chief risk factor for
      lifestyle-related diseases such as cardiovascular disease and diabetes, but the
      molecular mechanisms that underlie the increase in the risk of such diseases
      conferred by aging remain unclear. Recently, genetic analyses using various
      animal models have identified molecules that are crucial for aging. These include
      components of the DNA repair system, the tumor suppressor pathway, the telomere
      maintenance system, the insulin/Akt pathway, and other metabolic pathways.
      Interestingly, most of the molecules that influence the phenotypic changes of
      aging also regulate cellular senescence, suggesting a causative link between
      cellular senescence and aging. This review examines the hypothesis that cellular
      senescence might contribute to lifestyle-related disease.

PMID- 21084759
TI  - Assessment of the aortic root using real-time 3D transesophageal
      echocardiography.
AB  - BACKGROUND: Precise evaluation of the aortic root geometry prior to transcatheter
      aortic valve implantation is important for procedural success in patients with
      aortic stenosis (AS). To determine the potential for 3-dimensional
      transesophageal echocardiography (3DTEE), the aims of the present study were: (1)
      to assess the accuracy of 3DTEE measurements of the aortic root using
      multidetector computed tomography (MDCT) as a reference, and (2) to examine
      whether aortic root geometry differs between patients with and without AS.
      METHODS AND RESULTS:   3DTEE and contrast-enhanced MDCT were performed in 35
      patients. Multiplanar reconstruction was used to measure the left ventricular
      outflow tract (LVOT) and aortic annulus diameter/area, aortic valve area (AVA),
      and distances between the annulus and coronary artery ostium. The same 3DTEE
      measurements were performed in patients with (n=71) and without AS (n=80). Aortic
      annular and LVOT areas measured by 3DTEE were slightly but significantly smaller
      compared with values obtained with MDCT. Both methods revealed that the aortic
      annulus and LVOT have an oval shape. Aortic annular and LVOT area, AVA and the
      distances between the aortic annulus and the coronary ostia correlated well
      between the 2 modalities. Only minor differences in aortic root geometry were
      observed between patients with AS and those without. CONCLUSIONS: The geometry of
      the aortic annulus can be reliably evaluated using 3DTEE as an alternative to
      MDCT for the assessment of aortic root.

PMID- 21084757
TI  - Cardiogenesis from human embryonic stem cells.
AB  - Over the past decade, the ability to culture and differentiate human embryonic
      stem cells (ESCs) has offered researchers a novel therapeutic that may, for the
      first time, repair regions of the damaged heart. Studies of cardiac development
      in lower organisms have led to identification of the transforming growth factor
      beta superfamily (eg, activin A and bone morphogenic protein 4) and the Wnt/beta
      catenin pathway as key inducers of mesoderm and cardiovascular differentiation.
      These factors act in a context-specific manner (eg, Wnt/beta-catenin is required
      initially to form mesoderm but must be antagonized thereafter to make cardiac
      muscle). Different lines of ESCs produce different levels of agonists and
      antagonists for these pathways, but with careful optimization, highly enriched
      populations of immature cardiomyocytes can be generated. These cardiomyocytes
      survive transplantation to infarcted hearts of experimental animals, where they
      create new human myocardial tissue and improve heart function. The grafts
      generated by cell transplantation have been small, however, leading to an
      exploration of tissue engineering as an alternate strategy. Engineered tissue
      generated from preparations of human cardiomyocytes survives poorly after
      transplantation, most likely because of ischemia. Creation of pre-organized
      vascular networks in the tissue markedly enhances survival, with human
      capillaries anastomosed to the host coronary circulation. Thus, pathways
      controlling formation of the human cardiovascular system are emerging, yielding
      the building blocks for tissue regeneration that may address the root causes of
      heart failure.

PMID- 21084760
TI  - Evaluation of pharmaceutical excipients as cosolvents in 4-methyl umbelliferone
      glucuronidation in human liver microsomes: applications for compounds with low
      solubility.
AB  - Standard incubation procedures for carrying out microsomal assays involve the use
      of less than 1% w/v organic solvents to minimize the potential inhibitory effects
      of organic solvents on metabolic activity. This presents a practical limitation
      for poorly soluble xenobiotics, which cannot be incubated at concentrations high
      enough to obtain a V(max), and therefore subsequent values for K(m) and Cl(int)
      cannot be calculated. Our goal was to study the application of a variety of
      pharmaceutical excipients to aid the solubilization of compounds in vitro in
      glucuronidation incubations, without affecting the reaction kinetics. In vitro
      glucuronidation incubations were carried out in human liver microsomes with 4
      methylumbelliferone (4-MU) and the kinetics of 4-MU glucuronidation in the
      presence of excipients were compared to that in control incubations without any
      excipients. In addition, IC(75) values were calculated for each excipient. We
      observed that HPBCD (Hydroxypropyl-beta-cyclodextrin) may be employed in in vitro
      glucuronidation incubations up to 0.5% w/v without affecting the Cl(int) of 4-MU.
      Although NMP (N-methyl-2-pyrrolidone) and DMA (N,N-dimethylacetamide); showed low
      IC(75) values approximately 0.1% w/v each, neither excipients altered the Cl(int)
      of 4-MUG (4-methylumbelliferyl-beta-D-glucuronide) formation. Our studies point
      toward possible applications of pharmaceutical excipients to carry out in vitro
      glucuronidation of substrates with poor aqueous solubility, in order to estimate
      Cl(int) and subsequently scaled organ clearance values.

PMID- 21084761
TI  - Genetic polymorphisms and haplotypes of por, encoding cytochrome p450
      oxidoreductase, in a Japanese population.
AB  - Cytochrome P450 oxidoreductase (POR) transfers electrons from NADPH to all
      microsomal cytochrome P450 (CYP) enzymes and is necessary for microsomal CYP
      activities. In this study, to find genetic variations and to elucidate the
      haplotype structures of POR, we comprehensively screened the genetic variations
      in the 5'-flanking region, all the exons and their flanking introns of POR for
      235 Japanese subjects. Seventy-five genetic variations including 26 novel ones
      were found: 7 were in the 5'-flanking region, 2 in the 5'-untranslated region (5'
      UTR, non-coding exon 1), 16 in the coding exons (10 nonsynonymous and 6
      synonymous), 45 in the introns, 4 in the 3'-UTR and 1 in the 3'-flanking region.
      Of these, 4 novel nonsynonymous variations, 86C>T (T29M), 1648C>T (R550W),
      1708C>T (R570C) and 1975G>A (A659T), were detected with allele frequencies of
      0.002. We also detected known nonsynonymous SNPs 683C>T (P228L), 1237G>A (G413S),
      1453G>A (A485T), 1508C>T (A503V), 1510G>A (G504R) and 1738G>C (E580Q) with
      frequencies of 0.002, 0.009, 0.002, 0.434, 0.002 and 0.002, respectively. Based
      on the linkage disequilibrium (LD) profiles, the analyzed region could be divided
      into two LD blocks. For Blocks 1 and 2, 14 and 46 haplotypes were inferred,
      respectively, and 2 and 6 common haplotypes found in more than 0.03 frequencies
      accounted for more than 81% of the inferred haplotypes. This study provides
      fundamental and useful information for the pharmacogenetic studies of drugs
      metabolized by CYPs in the Japanese population.

PMID- 21084762
TI  - Involvement of the immune system in idiosyncratic drug reactions.
AB  - There is strong evidence that most idiosyncratic drug reactions (IDRs) are immune
      mediated and are caused by reactive metabolites of a drug rather than by the drug
      itself. Several hypotheses have been proposed by which a drug could induce an
      immune response. The major hypotheses are the hapten hypothesis and the danger
      hypothesis; however, the characteristics and spectrum of IDRs are different with
      different drugs, and this likely reflects mechanistic differences; therefore, no
      one hypothesis is likely to explain all IDRs. Some IDRs appear to involve
      epigenetic effects, direct activation of antigen-presenting cells, or disturbing
      the normal balance of the immune system. It has been suggested that many cases of
      idiosyncratic liver injury are not immune-mediated, and other mechanisms such as
      mitochondrial injury may be involved. It is essential that any hypothesis be
      consistent with the clinical characteristics of the IDR. Although the
      characteristics of most idiosyncratic liver injury do not suggest that
      mitochondria are the major target, it is quite possible that milder mitochondrial
      injury could stimulate an immune-mediated reaction. The observation that IDRs can
      vary widely among different drugs and different patients is most easily explained
      by an immune mechanism in which the target of the immune response is different.

PMID- 21084763
TI  - Assessment of the pharmacokinetic interaction between the novel DPP-4 inhibitor
      linagliptin and a sulfonylurea, glyburide, in healthy subjects.
AB  - The aim of this study was to investigate the effect of the dipeptidyl peptidase-4
      inhibitor linagliptin on the pharmacokinetics of glyburide (a CYP2C9 and CYP3A4
      substrate) and vice versa. This randomized, open-label, three-period, two-way
      crossover study examined the effects of co-administration of multiple oral doses
      of linagliptin (5 mg/day * 6 days) and single doses of glyburide (1.75 mg/day * 1
      day) on the relative bioavailability of either compound in healthy subjects (n =
      20, age 18-55 years). Coadministration of glyburide did not alter the steady
      state pharmacokinetics of linagliptin. Geometric mean ratios (GMRs) [90% CI] for
      (linagliptin + glyburide)/linagliptin AUC(tau,ss) and C(max,ss) were 101.7% [97.7
      105.8%] and 100.8% [89.0-114.3%], respectively. For glyburide, there was a slight
      reduction in exposure of ~14% when coadministered with linagliptin (GMRs [90% CI]
      for (glyburide + linagliptin)/glyburide AUC(0-infinity) and C(max) were 85.7%
      [79.8-92.1%] and 86.2% [79.6-93.3%], respectively). However, this was not seen as
      clinically relevant due to the absence of a reliable dose-response relationship
      and the known large pharmacokinetic interindividual variability of glyburide.
      These results further support the assumption that linagliptin is not a clinically
      relevant inhibitor of CYP2C9 or CYP3A4 in vivo. Coadministration of linagliptin
      and glyburide had no clinically relevant effect on the pharmacokinetics of
      linagliptin or glyburide. Both agents were well tolerated and can be administered
      together without the need for dosage adjustments.

PMID- 21084764
TI  - Influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian
      patients.
AB  - Warfarin exhibits wide interpatient variability in dosing requirements. Recent
      studies have shown a novel polymorphism (rs2108622, V433M) in the CYP4F2 gene to
      be associated with variability in warfarin requirements in Caucasians. The
      purpose of this study was to evaluate the impact of rs2108622 on warfarin dose
      requirements in the Asian population. The mean warfarin dose was found to be
      significantly lower in patients carrying homozygous wild-type allele CC when
      compared with patients carrying variant alleles CT and TT (CC vs CT+TT: 3.0
      mg/day vs 3.75 mg/day, p = 0.033). In patients harboring VKORC1 diplotypes
      associated with low warfarin requirements, a linear regression model which
      included age, weight, CYP2C9 and CYP4F2 variants accounted for 38% of the
      variability in warfarin dose. Approximately 11% of the dose variation was
      explained by CYP4F2 rs2108622 (p = 0.004). The influence of rs2108622 in patients
      harboring VKORC1 diplotypes associated with high warfarin requirements was not
      significant. This study suggests that CYP4F2 rs2108622 may significantly affect
      warfarin dose requirements in carriers of VKORC1 low-dose-associated diplotypes.

PMID- 21084765
TI  - PDZK1 regulates organic anion transporting polypeptide Oatp1a in mouse small
      intestine.
AB  - Recent studies indicate that various members of the organic anion transporting
      polypeptide (OATP) family are expressed on apical membranes of the small
      intestine. In the present study, we investigated possible interaction of Oatp
      with the PDZ protein PDZK1 in mouse small intestine, using [3H]estrone-3-sulfate
      (E3S) as a typical substrate. After intraduodenal administration, the level of
      [3H]E3S appearing in the portal vein of pdzk1 gene knockout (pdzk1(-/-)) mice was
      much lower than that in wild-type mice. Lower intestinal absorption of [3H]E3S in
      pdzk1(-/-) mice was confirmed in Ussing-type chamber experiments, which showed
      smaller uptake of [3H]E3S from the apical side in intestinal tissues of pdzk1(-/
      ) mice compared with wild-type mice. The kinetics and inhibition profile of
      [3H]E3S uptake in the Ussing-type chamber were similar to those in HEK293 cells
      stably expressing Oatp1a5, suggesting involvement of Oatp1a5 in [3H]E3S uptake.
      Immunoreactivity to anti-Oatp1a antibody was colocalized with PDZK1 in the small
      intestine of wild-type mice, whereas apical localization of Oatp1a protein was
      reduced in pdzk1(-/-) mice. An immunoprecipitation study revealed physical
      interaction of PDZK1 with Oatp1a. Thus, PDZK1 appears to act as an adaptor for
      Oatp1a. This is the first demonstration of a regulatory protein directly
      interacting with small-intestinal OATP.

PMID- 21084766
TI  - Enhancement of drug solubility and absorption by copolymers of 2
      methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate.
AB  - Poly[2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate]s (PMBs)
      are water-soluble solid copolymers of 2-methacryloyloxyethyl phosphorylcholine
      (MPC) and n-butyl methacrylate with a molecular weight of 30,000 (PMB50T) or
      100,000 (PMB100T). Here, we characterized the solubilizing properties of PMBs
      using miconazole (MCZ), vidarabine (Ara-A) and griseofulvin (GRF), which are
      class 2, 3 and 4 compounds, respectively, in the Biopharmaceutics Classification
      System (BCS). Moreover, we evaluated the enhancement of gastric absorption of GRF
      dissolved in PMB solutions and the toxicity of PMBs in rats. PMB50T solution
      dramatically increased the solubility of GRF and MCZ compared with Ara-A, and
      these drugs became more soluble as the concentration of PMB50T was increased. The
      solubility of GRF in 10% PMB solutions was higher than with any other tested
      aqueous solubilizer. When a solution of GRF (20 mg/10 mL/kg) in 10% PMB was
      orally administered to rats, GRF absorption was greatly increased compared with
      that following administration of a suspension in water or Gelucire. After
      repeated oral administration of PMBs once daily for 14 successive days, no organ
      lesions or changes in biochemical parameters were observed. Thus, the polymers
      are expected to be useful and safe solubilizers and oral absorption enhancers for
      poorly soluble lipophilic drugs.

PMID- 21084767
TI  - Effects of sodium bicarbonate and ammonium chloride pre-treatments on PEPT2
      (SLC15A2) mediated renal clearance of cephalexin in healthy subjects.
AB  - PEPT2 mediates the H(+) gradient-driving reabsorption of di- and tri-peptides,
      and various peptidomimetic compounds in the kidney. This study examines the
      influence of urinary pH modification through sodium bicarbonate and ammonium
      chloride pre-treatments on the function of PEPT2 in healthy subjects, using
      cephalexin as the probe drug. Sixteen male subjects received a single oral dose
      of 1000 mg cephalexin under ammonium chloride and sodium bicarbonate treatment,
      respectively, with a wash-out period of one week. The study subjects were
      genotyped for PEPT2 polymorphic variants. Cephalexin concentrations in plasma and
      urine were determined by high performance liquid chromatography. The mean renal
      clearance of cephalexin was significantly higher under ammonium chloride
      treatment than that under sodium bicarbonate treatment (P < 0.01). This
      difference was significant for PEPT2*2/*2 (P = 0.017) but not for PEPT2*1/*1 (P =
      0.128). No differences were observed for other pharmacokinetic parameters. The
      findings of this study suggest that urinary pH changes may alter the
      pharmacokinetics of PEPT2's substrates. This effect was more obvious for the
      PEPT2*2/*2.

PMID- 21084769
TI  - Retraction: Focusing on the influence of testosterone on leptin and resistin in
      male hypogonads: missing link in insulin resistance?
AB  - This article released online on September 22, 2010 as advance publication was
      withdrawn at the request of the authors.

PMID- 21084768
TI  - Effect of tea beverages on aldehyde oxidase activity.
AB  - Aldehyde oxidase (AO) plays an important role in metabolizing antitumor and
      antiviral drugs, including methotrexate, cyclophosphamide and acyclovir. Green
      tea and its catechins have been shown to modulate the activities of various
      xenobiotic-metabolizing cytochrome P450 species, both in vivo and in vitro, but
      their effect on AO has not been studied. Therefore, we evaluated the effect of
      tea beverages on AO activity in rat and human liver cytosol. We also investigated
      the influence of several catechins on AO activity in rat liver cytosol. AO
      activity was evaluated in terms of oxidation of N-1-methylnicotinamide to N-1
      methyl-2-pyridone-5-carboxamide and N-1-methyl-4-pyridone-3-carboxamide. Bottled
      green tea beverages at 10% (vol/vol) inhibited AO activity by 90.0-93.5%, while
      at 1.0% (vol/vol), they reduced AO activity by 73.9-90.0%. At 0.1% (vol/vol),
      green tea II and III, which have high contents of catechins and their
      derivatives, inhibited AO activity by 24.3% and 38.8%, respectively. Bottled
      mineral water had no effect. AO activity was inhibited potently by epicatechin
      and epicatechin gallate. These results indicate that the AO-inhibitory activity
      of tea beverages is predominantly due to catechins and their derivatives. Thus,
      consumption of tea beverages may cause a decrease of AO activity, which may
      result in reduced clearance of drugs that are AO substrates.

PMID- 21084770
TI  - Correlation between baseline serum 1,5-anhydroglucitol levels and 2-hour post
      challenge glucose levels during oral glucose tolerance tests.
AB  - Since there is increasing evidence that postprandial hyperglycemia is a risk
      factor for the development of macrovascular complications, it is important to
      predict postprandial hyperglycemia in the early stages of glucose intolerance,
      and routine medical checkups provide a good opportunity to do so. The aim of this
      study was to evaluate the usability of 1,5-anhydroglucitol (1,5-AG) in routine
      medical checkups. The subjects were 77 Japanese men who participated in a routine
      medical checkup. First, we performed 75 g oral glucose tolerance tests (OGTTs),
      and examined the changes in glucose and 1,5-AG levels measured at 0, 30, 60, 90,
      120, and 180 minutes (min). 1,5-AG levels did not significantly change until 90
      min after the glucose load. Second, a linear regression analysis showed an
      inverse correlation between the 2-hour post-challenge glucose (2h-PG) and
      baseline 1,5-AG levels during the OGTT (P = 0.001, r(2) = 0.13), and the
      correlation was still significant after adjustment for age (2h-PG = 170 + 0.83 *
      (age in years) - 3.23 * (1,5-AG), P = 0.002, adjusted r(2) = 0.12). Finally, to
      investigate the test characteristics of 1,5-AG levels as a predictor of a 2h-PG
      level >=200 mg/dL, we plotted a receiver operating characteristic (ROC) curve.
      The area under the ROC curve was 0.78, and the maximal sum of sensitivity and
      specificity (78% and 72%, respectively) was obtained at a 1,5-AG cutoff level of
      <14.2ug/mL. We conclude that 1,5-AG values may provide an ancillary predictor of
      2h-PG of 75 g OGTTs in routine medical checkups.

PMID- 21084771
TI  - Isolation of rotational isomers and developments derived therefrom.
AB  - Isolation of rotational isomer models of ethane-type molecules is described. We
      could experimentally prove that, if rotational isomers whose molecular shape was
      chiral, the molecule could be optically active, even though it did not carry an
      asymmetric carbon atom. As an extension, other types of stereochemically
      fundamental and optically active molecules were isolated and their absolute
      stereochemistry was determined. One example is the model of meso-tartaric acid,
      for which optical inactivity had been attributed to internal compensation but is
      now explained as follows. On dissolution of meso-tartaric acid in a solvent, the
      molecule gives two kinds of conformers, one of which is a C(i) molecule and the
      other is a C(1) molecule. Although the latter is intrinsically optically active,
      the optical activity is cancelled by its enantiomer. The theory of internal
      compensation is recommended to be abandoned. As an extension to another area,
      some reactions of conformers are also discussed.

PMID- 21084772
TI  - Fabrication, properties, and applications of porous metals with directional
      pores.
AB  - Lotus-type porous metals with aligned long cylindrical pores are fabricated by
      unidirectional solidification from the melt with a dissolved gas such as
      hydrogen, nitrogen, or oxygen. The gas atoms can be dissolved into the melt via a
      pressurized gas atmosphere or thermal decomposition of gaseous compounds. Three
      types of solidification techniques have been developed: mold casting, continuous
      zone melting, and continuous casting techniques. The last method is superior from
      the viewpoint of mass production of lotus metals. The observed anisotropic
      behaviors of the mechanical properties, sound absorption, and thermal
      conductivity are inherent to the anisotropic porous structure. In particular, the
      remarkable anisotropy in the mechanical strength is attributed to the stress
      concentration around the pores aligned perpendicular to the loading direction.
      Heat sinks are a promising application of lotus metals due to the high cooling
      performance with a large heat transfer.

PMID- 21084774
TI  - Subterranean electrical structure of Kozu-shima volcanic island, Japan.
AB  - Following the electric current injection experiment carried out in 2009, a VLF-MT
      (Very Low Frequency Magnetotelluric) survey has been conducted in Kozu-shima
      Island to obtain further information on the subterranean electrical structure
      that might help understanding the results of our monitoring of geoelectric
      potentials. A number of VAN-type pre-seismic geoelectric potential anomalies were
      observed in 1997-2000, even showing a remarkable "Selectivity". However, similar
      pre-seismic anomalies were not observed during the Izu-Island volcano-seismic
      swarm 2000. All these observations would require extremely high degree of
      heterogeneity in the subterranean electrical structure of the volcanic island and
      its possible time changes. Several correlations between the results of this
      survey and the volcanic geology of the island and ground water distribution were
      found. Further investigation is needed for a complete explanation of the observed
      phenomena.

PMID- 21084773
TI  - Recent insights into iron homeostasis and their application in graminaceous
      crops.
AB  - Higher plants utilize various mechanisms to maintain iron homeostasis. To acquire
      sparingly soluble iron from the rhizosphere, graminaceous plants synthesize
      natural iron (III) chelators known as mugineic acid family phytosiderophores
      (MAs). Recent research has uncovered various genes involved in iron uptake and
      translocation, as well as factors regulating the expression of these genes,
      especially in rice. Manipulation of these molecular components is used to produce
      transgenic crops with enhanced tolerance to iron deficiency, or with a high seed
      iron content. Since iron homeostasis is closely linked to that of other mineral
      elements, an understanding of this phenomenon will serve as the basis for the
      production of crops with low concentrations of toxic metals and transgenic plants
      for phytoremediation.

PMID- 21084775
TI  - Single channel properties of lysenin measured in artificial lipid bilayers and
      their applications to biomolecule detection.
AB  - Single channel currents of lysenin were measured using artificial lipid bilayers
      formed on a glass micropipette tip. The single channel conductance for KCl, NaCl,
      CaCl(2), and Trimethylammonium-Cl were 474 +/- 87, 537 +/- 66, 210 +/- 14, and
      274 +/- 10 pS, respectively, while the permeability ratio P(Na)/P(Cl) was 5.8. By
      adding poly(deoxy adenine) or poly(L-lysine) to one side of the bilayer, channel
      currents were influenced when membrane voltages were applied to pass the charged
      molecules through the channel pores. Current inhibition process was concentration
      dependent with applied DNA. As the current fluctuations of alpha-hemolysin
      channels is often cited as the detector in a molecular sensor, these results
      suggest that by monitoring channel current changes, the lysenin channel has
      possibilities to detect interactions between it and certain biomolecules by its
      current fluctuations.

PMID- 21084776
TI  - Management of complicated urinary tract infections in the era of antimicrobial
      resistance.
AB  - Complicated urinary tract infections (cUTIs) are a major cause of hospital
      admissions and are associated with significant morbidity and health care costs.
      Patients presenting with a suspected UTI should be screened for the presence of
      complicating factors, such as anatomic and functional abnormalities of the
      genitourinary tract. In the setting of cUTIs, the etiology and susceptibility of
      the causative organism is not predictable; therefore, when infection is
      suspected, patients should undergo a urinalysis in addition to culture and
      sensitivity testing. Although not warranted in all cases of complicated
      pyelonephritis, blood cultures are appropriate in some clinical settings. With
      the increased prevalence of antimicrobial resistance, and the lack of well
      designed clinical trials, treatment of cUTIs can be challenging for clinicians.
      Although resistant organisms are not always implicated as the causative agent,
      all patients with cUTIs should be assessed for predisposing risk factors.
      Consideration of an optimal antimicrobial agent should be based on local
      resistance patterns, patient-specific factors, including anatomic site of
      infection and severity of disease, pharmacokinetic and pharmacodynamic
      principles, and cost. Resistance to first-line antimicrobial agents, including
      fluoroquinolones, has become increasingly common in Escherichia coli.
      Fluoroquinolones should not be used as a first-line option for empiric treatment
      of serious cUTIs, especially when patients exhibit risk factors for harboring a
      resistant organism, such as previous or recent use of fluoroquinolones.
      Fluoroquinolones, trimethoprim-sulfamethoxazole, and nitrofurantoin are still
      appropriate empiric options for mild lower cUTIs. However, empiric treatment for
      serious cUTIs, where risk factors for resistant organisms exist, should include
      broad-spectrum antibiotics such as carbapenems or piperacillin-tazobactam. Once
      organisms and susceptibilities are identified, treatment should be targeted
      accordingly. Nitrofurantoin and fosfomycin have limited utility in the setting of
      cUTIs and should be reserved as alternative treatment options for lower cUTIs
      following confirmation of the causative organism. Aminoglycosides, tigecycline,
      and polymyxins can be used for the treatment of serious cUTIs when first-line
      options are deemed to be inappropriate or patients fail therapy. The duration of
      treatment for cUTIs has not been well established; however, treatment durations
      can range from 1 to 4 weeks based on the clinical situation.

PMID- 21084777
TI  - Methicillin-resistant Staphylococcus aureus: a community health threat.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common causes
      of infections, has been traditionally recognized as a nosocomial pathogen.
      However, in recent years, its epidemiology has radically changed, being now
      observed even more frequently in the community, and accounting for > 50% of
      staphylococcal infections in the US outpatient setting. Community-acquired (CA)
      MRSA strains typically cause infections among otherwise healthy individuals, with
      risk factors differing from those of nosocomial MRSA. The clinical manifestations
      may range from a furuncle to life-threatening infections, such as necrotizing
      fasciitis and pneumonia. The antibiotic treatment of these infections may also
      differ because CA-MRSA strains often retain susceptibility to antimicrobials
      other than glycopeptides and newer agents. Moreover, the production of toxins,
      such as the Panton-Valentine leukocidin (PVL), should influence the antibiotic
      choice because in these cases the use of a combination therapy with antimicrobial
      agents able to decrease toxin production is suggested. There are still many
      unanswered key questions regarding the epidemiology, prevention, and treatment of
      CA-MRSA infections. This article reviews current knowledge of CA-MRSA.

PMID- 21084778
TI  - Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized
      individuals and Pneumocystis pneumonia patients from Spain.
AB  - Cotrimoxazole, an association of trimethoprim and sulfamethoxazole, and dapsone,
      are mainstays for the prophylaxis and treatment of Pneumocystis pneumonia (PcP).
      The inability to culture Pneumocystis prevents routine susceptibility testing and
      detection of drug resistance. Instead, molecular techniques have been used to
      detect Pneumocystis jiroveci dihydropteroate synthase (DHPS) mutations that cause
      sulfa resistance in other microorganisms. The most frequent DHPS mutations occur
      at nucleotide positions 165 and 171, which lead to an amino acid change at
      positions 55 and 57. Several studies suggest that these mutations are associated
      with the failure of chemoprophylaxis for PcP. The aim was to establish the
      frequency and characteristics of P jiroveci DHPS mutations among colonized
      individuals and PcP patients from Spain. A total of 50 colonized individuals and
      25 PcP patients were studied. DHPS polymorphisms were identified by restriction
      fragment length polymorphism assay. The analysis provided a rate of 28% of DHPS
      gene mutations in our population, with the presence of all possible polymorphisms
      described. The presence of mutations was higher in PcP patients than in colonized
      subjects (40% vs 22%), probably because of the chemoprophylaxis used in PcP
      patients. The comparison between patients with and without DHPS mutations did not
      show statistical differences due to age, sex, steroid use, sulfa drug exposure,
      or smoking. A high rate of DHPS mutations in our area of Spain, not only confined
      to patients previously exposed to sulfa drugs, is shown in this study. As well as
      PcP patients, colonized individuals who harbor P jiroveci strains with DHPS
      mutations could play a major role in the transmission cycle of these mutations,
      representing a reservoir and source of infection for susceptible individuals.
      Further research is thus warranted to assess the true scope of the problem and to
      design rational preventive strategies.

PMID- 21084779
TI  - Acute kidney injury: current perspectives.
AB  - Acute kidney injury (AKI) increases morbidity and mortality, particularly for the
      critically ill. Recent definitions standardizing AKI to reflect graded changes in
      serum creatinine and urine output (per the Risk, Injury, Failure, Loss, and End
      stage renal failure [RIFLE] and Acute Kidney Injury Network [AKIN] criteria) with
      severity of renal injury and developments in AKI pathobiology are being utilized
      to identify biomarkers of early kidney injury. These developments may be useful
      in the early intervention of preventing AKI. Although there has been progress in
      the management of AKI, therapeutic challenges include appropriate prophylaxis
      prior to contrast administration, use of diuretics, vasopressors, and the type
      and dose of renal replacement therapy. Future use of bioartificial dialyzers,
      plasma therapies, and the possibility of stem cell regeneration of injured kidney
      tissue are being actively investigated to provide alternative treatment options
      for AKI. This review aims to provide an overview of current practices, available
      therapies, and continued research in AKI therapy.

PMID- 21084780
TI  - Low agreement between the modified diet and renal disease formula and the
      Cockcroft-Gault formula for assessing chronic kidney disease in cognitively
      impaired elderly outpatients.
AB  - OBJECTIVE: Chronic kidney disease is a global public health concern. Glomerular
      filtration rate (GFR) prediction based on serum creatinine is used to assess
      renal function in the elderly. The Cockcroft-Gault (CG) formula, based on body
      surface area (CG/BSA formula), and the Modified Diet and Renal Disease formula
      (MDRD formula) are commonly used in assessing renal function in clinical
      practice. The objective of this study was to investigate the agreement between
      the GFR estimate, CG/BSA formula, and the MDRD formula in elderly outpatients.
      METHODOLOGY: An outpatient chart review was conducted on consecutive elderly
      patients aged >= 65 years over a 9-month period. Data regarding age, gender,
      cognitive status, clock drawing, weight, height, and serum creatinine were
      collected. Pearson's correlation coefficient, Bland-Altman plot, and kappa
      statistics were used for statistical analysis. RESULTS: Of the 170 patients who
      participated in the study, 71% were cognitively impaired or had dementia. Using
      the CG/BSA formula, 79% of the patients had stage 3 renal disease (GFR< 60
      mL/min); only 56% were diagnosed as such using the MDRD formula. There was a high
      correlation between the CG/BSA and MDRD formulas (Pearson correlation
      coefficient, 0.88; P < 0.0001). However, the kappa statistic was 0.47, indicating
      low agreement between the 2 formulas. CONCLUSION: The diagnosis of having stage 3
      chronic kidney disease depended on whether the CG/BSA or MDRD formula was used. A
      17% discordance rate (9.61 mL/min) was seen between the MDRD and CG/BSA formulas
      for estimating GFR, and there was low agreement between the 2 formulas. Further
      studies are needed to assess which predictive formula is appropriate for elderly
      patients.

PMID- 21084781
TI  - Multiple paragangliomas in a pregnant patient with a succinate dehydrogenase B
      mutation.
AB  - In this case report, we document the clinical course, laboratory findings, and
      imaging findings of a 21-year-old pregnant woman with multiple paragangliomas due
      to a succinate dehydrogenase B (SDHB) mutation. We also review the literature on
      previously reported cases. The patient presented with nausea, palpitations,
      angina, and amenorrhea. Her blood pressure was 170/100 mm Hg and her beta-human
      chorionic gonadotropin was positive. Her blood pressure remained high despite
      phenoxybenzamine titration. A 24-hour urine analysis revealed elevated plasma
      metanephrines. Imaging was initially deferred due to early gestational age. After
      the patient terminated the pregnancy, magnetic resonance imaging revealed a left
      suprarenal mass, a mass at the aortic bifurcation, and a left periaortic mass.
      Her blood pressure was controlled on phenoxybenzamine and labetalol. The masses
      were excised. Pathology revealed paragangliomas. Genetic testing revealed
      mutation in the SDHB gene. One month later, her blood pressure was 122/86 mm Hg
      off of medication. Paraganglioma/pheochromocytoma should be suspected when
      hypertension occurs early in pregnancy. Genetic testing is important, as this may
      impact future offspring.

PMID- 21084782
TI  - Erectile dysfunction may improve by blood pressure control in patients with high
      risk hypertension.
AB  - BACKGROUND: Blood pressure (BP) control induces reductions in target-organ damage
      and cardiovascular events. Erectile dysfunction (ED) is a multifactorial disease
      related to cardiovascular disease, but its relationship with BP control has not
      been extensively studied. AIMS: We describe the effect of BP control on ED in
      patients with high-risk hypertension who were treated with beta-blockers. STUDY
      DESIGN: This was a cross-sectional and observational study of male patients with
      hypertension treated with any beta-blocking agent for >= 6 months. Erectile
      dysfunction was assessed by the International Index of Erectile Function (IIEF).
      Statistical analysis was performed using a Chi-square test, Fisher's exact test,
      covariance analysis, and stepwise logistic regressions. RESULTS: A total of 1242
      patients were studied; 33.7% had controlled BP. Patients with uncontrolled BP had
      slightly higher mean age (64.4 years vs 58.6 years) and higher prevalence of
      diabetes and cardiac and noncardiac comorbidities. Patients with controlled BP
      had a lower crude and adjusted prevalence of ED. Erectile dysfunction was
      significantly lower in patients with controlled BP in the 2 older age quartiles
      (> 59 years). Multivariate analyses, adjusted by age, clinical features, and
      medical treatments were conducted separately in patients within the 2 younger and
      older age quartiles. In patients in the 2 younger quartiles, ED was only
      independently and inversely associated with nebivolol treatment (odds ratio [OR],
      0.22; 95% confidence interval [CI], 0.05-0.88). Conversely, BP control (OR, 0.48;
      95% CI, 0.26-0.89), diabetes (OR, 2.64; 95% CI, 1.32-5.28), and peripheral artery
      disease (OR, 3.80; 95% CI, 1.20-12.00) were independently associated with ED in
      patients in the older 2 age quartiles. CONCLUSION: In patients with high-risk
      hypertension treated with beta-blockers, BP control was associated with a lower
      prevalence of ED, independently of age, cardiovascular disease, and medical
      treatments. The effect of BP control was higher in older patients.

PMID- 21084783
TI  - Efficacy and safety of olmesartan medoxomil in patients with stage 1
      hypertension: blood pressure lowering and goal achievement.
AB  - Hypertension is a known risk factor for cardiovascular events and mortality. The
      risk of cardiovascular events increases with age and is linear above 115/75 mm
      Hg. It also doubles for every 20/10-mm Hg elevation beyond this level and at
      every age level. Although guidelines vary somewhat by country, the seventh report
      of the Joint National Committee on Prevention, Detection, Evaluation, and
      Treatment of High Blood Pressure recommends a blood pressure (BP) goal of <
      140/90 mm Hg for patients with uncomplicated hypertension and < 130/80 mm Hg for
      patients with type 2 diabetes mellitus (T2DM) or renal disease. Based on clinical
      evidence, patients with stage 1 hypertension (seated cuff systolic BP of 140-159
      mm Hg or diastolic BP of 90-99 mm Hg) should be treated to targeted BP levels to
      reduce cardiovascular morbidity and mortality. The angiotensin II receptor
      blockers (ARBs) are well tolerated and demonstrate significant BP reduction.
      Olmesartan medoxomil (OM), an ARB, has been well studied and achieves significant
      BP lowering and goal achievement with good tolerability. Moreover, combination
      therapy comprising OM plus hydrochlorothiazide can significantly increase BP goal
      achievement without significantly increasing adverse events. This review
      evaluates clinical efficacy and safety data from 5 OM-based studies: 4 dose
      titration studies and 1 factorial study. Study results demonstrate that OM +/-
      hydrochlorothiazide is highly effective in reducing BP while enabling a majority
      of patients with stage 1 hypertension to achieve BP goal. In addition, OM
      tolerability data showed that the high achievement of BP goals was not attained
      at the expense of increased adverse events. This treatment is associated with low
      discontinuation rates, even in elderly patients and individuals with T2DM. The
      clinical data presented in this review support OM-based therapy as a rational and
      safe therapeutic option for patients with stage 1 hypertension.

PMID- 21084784
TI  - Cardiopulmonary exercise testing: relevant but underused.
AB  - Cardiopulmonary exercise testing (CPX) is a relatively old technology, but has
      sustained relevance for many primary care clinical scenarios in which it is,
      ironically, rarely considered. Advancing computer technology has made CPX easier
      to administer and interpret at a time when our aging population is more prone to
      comorbidities and higher prevalence of nonspecific symptoms of exercise
      intolerance and dyspnea, for which CPX is particularly useful diagnostically and
      prognostically. These discrepancies in application are compounded by patterns in
      which CPX is often administered and interpreted by cardiology, pulmonary, or
      exercise specialists who limit their assessments to the priorities of their own
      discipline, thereby missing opportunities to distinguish symptom origins. When
      used properly, CPX enables the physician to assess fitness and uncover
      cardiopulmonary issues at earlier phases of work-up, which would therefore be
      especially useful for primary care physicians. In this article, we provide an
      overview of CPX principles and testing logistics, as well as some of the clinical
      contexts in which it can enhance patient care.

PMID- 21084785
TI  - Opioid therapy for osteoarthritis and chronic low back pain.
AB  - BACKGROUND: Chronic low back pain (CLBP) and osteoarthritis (OA) of any joint are
      highly prevalent, occurring in > 50% of US adults aged >= 60 years. Opioids are
      prescribed more frequently for CLBP and OA than for any other noncancer pain, and
      the judicious use of opioids is recommended by treatment guidelines for the
      management of CLBP and OA pain. OBJECTIVE: To review the appropriate role of
      opioid analgesics in the treatment of patients with moderate-to-severe pain due
      to CLBP or OA and provide recommendations for best practices when prescribing
      opioids. METHODS: Articles were identified through a search of PubMed. Additional
      references were identified for inclusion from the reference lists of articles
      identified via the literature search, treatment guidelines, and Cochrane Reviews.
      RESULTS: The available data suggest that opioid therapy represents a valuable
      treatment option in patients who do not respond to other analgesics and in whom
      the potential benefits of treatment outweigh the potential risks. Prescribing
      physicians need to perform vigilant patient screening and monitoring for signs of
      abuse, intervene promptly to manage or prevent adverse events and drug
      interactions, tailor opioid therapy to individual patients' comorbidities, and
      know how to switch or rotate opioids to find the best treatment option.
      CONCLUSIONS: Prescribers need to understand the place of opioid therapy in a
      multimodal treatment program that includes patient rehabilitation to reduce pain
      and improve function. The analgesic benefits of opioids must be balanced against
      concerns about addiction and abuse, adverse events, and their potential impact on
      other aspects of treatment.

PMID- 21084786
TI  - Topical nonsteroidal anti-inflammatory drugs for osteoarthritis.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of the treatment of
      osteoarthritis (OA) but have dose- and age-related risks of gastrointestinal,
      cardiovascular, and renal adverse events (AEs). As a result, US and international
      guidelines recommend caution when prescribing oral NSAIDs, particularly in older
      patients and those with significant comorbidities. For OA of the hands and knees,
      topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic
      distribution. Treatment-related cardiovascular, renal, and other serious AEs with
      topical NSAIDs have not been reported. At present, only 2 topical NSAIDs are
      approved in the United States for the treatment of OA: diclofenac sodium 1% gel
      for hand or knee OA and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide
      solution for knee OA. Clinical trial data for these products have demonstrated
      efficacy superior to placebo or similar to oral diclofenac with AE profiles
      similar to placebo, except for application site reactions. In large double-blind
      trials, gastrointestinal AEs were infrequent and did not include ulcers,
      perforations, or bleeding. The purpose of this brief review is to examine the
      data from controlled double-blind trials evaluating the use of topical NSAIDs in
      patients with OA. Articles included were identified via a search of PubMed
      covering the period from January 1, 2005 through March 31, 2010. Reference lists
      from OA treatment guidelines and meta-analyses were reviewed for additional
      citations of importance.

PMID- 21084787
TI  - Aerobic physical exercise as a possible treatment for neurocognitive dysfunction
      in bipolar disorder.
AB  - BACKGROUND: Neurocognitive dysfunction associated with bipolar disorder (BD) is
      pervasive, persistent across illness phases, and is demonstrated to predispose
      and portend psychosocial impairment. Moreover, no approved therapies for various
      phases of BD have been shown to reliably improve any dimension of neurocognitive
      performance. In this article, we emphasize that aerobic physical exercise is a
      viable neurocognitive-enhancing adjunctive treatment for patients with BD. The
      overarching aim of this review is to emphasize that aerobic physical exercise is
      a viable neurocognitive-enhancing adjunctive treatment for patients with BD.
      METHODS: We conducted PubMed and Google Scholar searches of all English-language
      articles published between January 1966 and February 2010 using the search terms
      bipolar disorder, major depressive disorder, depression, exercise, and physical
      activity cross-referenced with each other and the following terms: cognition,
      executive function, learning, memory, attention, emotion, and behavior. Articles
      selected for review were based on adequacy of sample size, use of standardized
      experimental procedures, validated assessment measures, and overall quality.
      RESULTS: Available studies have documented an array of persisting neurocognitive
      deficits across disparate bipolar populations. Abnormalities in verbal working
      memory are highly replicated; deficits in executive function, learning,
      attention, and processing speed are also a consistent abnormality. The effect
      sizes of neurocognitive deficits in BD are intermediate between those reported in
      schizophrenia and major depressive disorder. Several original reports and reviews
      have documented the neurocognitive-enhancing effects of aerobic exercise in the
      general population as well as across diverse medical populations and ages.
      Proposed mechanisms involve nonexclusive effects on neurogenesis, neurotrophism,
      immunoinflammatory systems, insulin sensitivity, and neurotransmitter systems.
      Each of these effector systems are implicated in both normal and abnormal
      neurocognitive processes in BD. CONCLUSION: Available evidence provides a
      rationale for empirically evaluating the neurocognitive benefits of aerobic
      exercise in BD.

PMID- 21084788
TI  - Vaginitis: diagnosis and management.
AB  - Vaginitis is one of the most common ambulatory problems to occur in women. It is
      a disorder responsible for > 10% of visits made to providers of women's health
      care. Although vaginal infections are the most common cause, other considerations
      include cervicitis, a normal vaginal discharge, foreign-body vaginitis, contact
      vaginitis, atrophic vaginitis, and desquamative inflammatory vaginitis. The
      medical history and examination are an important source of clues to the
      underlying diagnosis. However, making a definitive diagnosis requires skillful
      performance of office laboratory procedures, including the vaginal pool wet mount
      examination, determination of the vaginal pH, and the whiff test. Vaginal and
      cervical cultures, nucleic acid tests, and point-of-care tests are available and
      may be required in selected patients. Once a specific diagnosis is made,
      effective therapy can be prescribed. Candida vaginitis is generally treated with
      either the vaginal administration of an imidazole or triazole antifungal agent or
      the prescription of oral fluconazole. Oral nitroimidazole agents, metronidazole
      or tinidazole, are the only effective treatments for trichomoniasis in the United
      States. Bacterial vaginosis, which has been linked to important gynecologic and
      pregnancy complications, can be treated with an available oral or topical agent
      containing either a nitroimidazole or clindamycin.

PMID- 21084789
TI  - Low sexual desire--is it all in her head? Pathophysiology, diagnosis, and
      treatment of hypoactive sexual desire disorder.
AB  - Hypoactive sexual desire disorder (HSDD) is thought to be the most prevalent form
      of female sexual dysfunction (FSD), affecting up to 1 in 10 US women. Hypoactive
      sexual desire disorder is defined by the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) as persistent or
      recurrent deficiency or absence of sexual fantasies and thoughts, and/or desire
      for, or receptivity to, sexual activity, which causes personal distress or
      interpersonal difficulties and is not caused by a medical condition or drug. This
      definition has recently received criticism and recommendations for changes
      encompass the inclusion of duration, intensity, and frequency, and the
      elimination of distress as a diagnostic criterion. More recently, it has been
      suggested that arousal and desire be combined into one disorder for the upcoming
      DSM-V. Causes of low desire include chronic medical conditions, medications,
      surgeries, and psychosocial factors, but not necessarily increased age; both pre-
      and postmenopausal women can have HSDD, although the frequency appears to vary by
      age. Sexual function requires the complex interaction of multiple
      neurotransmitters and hormones, both centrally and peripherally, and sexual
      desire is considered the result of a complex balance between inhibitory and
      excitatory pathways in the brain. For example, dopamine, estrogen, progesterone,
      and testosterone play an excitatory role, whereas serotonin and prolactin are
      inhibitory. Thus, decreased sexual desire could be due to a reduced level of
      excitatory activity, an increased level of inhibitory activity, or both. A number
      of validated self-report and clinician-administered instruments are available for
      assessing female sexual function; however, most have been used primarily in
      clinical research trials. The Decreased Sexual Desire Screener (DSDS) was
      developed for practicing clinicians who are neither trained nor specialized in
      FSD to assist in making an accurate diagnosis of generalized acquired HSDD. As
      our understanding of the pathophysiology of HSDD increases, it may become easier
      for physicians to identify and treat women with low sexual desire.

PMID- 21084790
TI  - Sitcom syncope: a case series and literature review of gelastic (laughter
      induced) syncope.
AB  - Syncope is a common complaint that is frequently evaluated without identifying a
      precipitating cause. Gelastic (laughter-induced) syncope is an uncommon and
      poorly understood condition. We describe 3 patients who experienced loss of
      consciousness during vigorous laughter. Each patient had an extensive medical
      evaluation, including a comprehensive history and physical examination, 12-lead
      electrocardiography, chest radiograph, routine blood analysis, polysomnography,
      tilt table testing, 2-dimensional transthoracic echocardiography, nuclear or
      echocardiographic stress testing, and 24-hour Holter monitoring. All 3 patients
      had an abnormal response to head-up tilt table testing, with either a significant
      decrease in systolic blood pressure or inappropriate heart rate response on
      achieving an upright position. These observations together with our review of the
      literature suggest that gelastic syncope may be a variant of vasodepressor
      syncope. Knowledge of this condition, its pathophysiology, and potential
      treatment options may be of value to clinicians when evaluating patients with
      unexplained loss of consciousness.

PMID- 21084791
TI  - The relationship between sleep disorders and stroke.
AB  - Although sleep appears to be a quiescent, passive state externally, there are a
      multitude of physiological changes occurring during sleep that can affect
      cerebral homeostasis and predispose individuals to cerebrovascular disorders.
      Therefore, it is not surprising that sleep-disordered breathing causes
      significant nocturnal perturbations, such as obstructive sleep apnea (OSA), that
      can lead to cerebrovascular disorders. There is evidence to suggest that OSA is a
      risk factor for stroke, although studies have not been able to clearly discern
      the absence or presence of OSA before the stroke event. Sleep-disordered
      breathing, such as OSA and central sleep apnea, can occur as a consequence of
      stroke. Fortunately, treating OSA appears to decrease morbidity and possibly
      mortality. Unfortunately, continuous positive airway pressure compliance in this
      population group is low, and significant efforts and resources may be needed to
      improve compliance and adherence. Various other sleep disorders, such as
      insomnia, fatigue, hypersomnia, and parasomnia, can occur following a stroke, and
      physicians treating patients following a stroke need to be aware of these
      disorders in order to effectively treat such patients.

PMID- 21084792
TI  - Improving the reporting of adverse drug reactions in the hospital setting.
AB  - The US Food and Drug Administration (FDA) is perceived by the public as having a
      substantial responsibility to ensure drug safety; however, the FDA has limited
      resources for active surveillance and relies on voluntary reporting of adverse
      events and potential adverse drug reactions. Studies have shown that
      underreporting of adverse events and adverse drug reactions is widespread.
      Furthermore, a review of several studies demonstrates that most adverse drug
      reactions are reported by pharmacists and nurses, with physicians reporting the
      fewest. The hospital setting, with its clearly defined patient population
      observed around the clock, is an ideal setting in which to identify potential
      adverse drug reaction signals and to report them to either the drug manufacturer
      or the FDA. In this article we describe the present system for addressing adverse
      events, obstacles to reporting them, and the important role any hospital
      physician could play in reporting adverse events and potential adverse drug
      reactions.

PMID- 21084793
TI  - Hypogonadism, erectile dysfunction, and type 2 diabetes mellitus: what the
      clinician needs to know.
AB  - Testosterone levels and erectile function are known to decline as men age,
      leading to hypogonadism and erectile dysfunction (ED). Men with type 2 diabetes
      mellitus (T2DM) have a particularly high prevalence of hypogonadism and ED. This
      population also has an increased risk for cardiovascular diseases, as well as
      exposure to other metabolic and cardiovascular risk factors, such as obesity.
      Several professional societies have recommended screening men with T2DM for
      testosterone deficiency. Hypogonadism is generally suspected when morning levels
      for total testosterone are < 300 ng/dL and clinical signs and symptoms typically
      associated with androgen deficiency are present. While hypogonadism and ED have
      emerged as predictors of cardiovascular disease and may respond to the lifestyle
      changes commonly recommended for patients with diabetes and the metabolic
      syndrome, the literature on whether treatment with testosterone supplementation
      affects outcomes beyond well-being and sexual function is still emerging. Primary
      care providers should be aware of this dysmetabolic cluster affecting their male
      patients and its importance, and, given the common occurrence of hypogonadism,
      ED, and T2DM, diagnosis of 1 of these conditions should elicit inquiry into the
      other 2 conditions.

PMID- 21084794
TI  - Denosumab for the management of postmenopausal osteoporosis.
AB  - View the National Osteoporosis Foundation Clinician's Guide Postmenopausal
      osteoporosis is a major concern to public health. Fractures are the major
      clinical consequence of osteoporosis and are associated with substantial
      morbidity, mortality, and health care costs. Despite the availability of
      screening and treatment guidelines, osteoporosis diagnosis and treatment remain
      low. Health care providers may consult guidelines in the clinical management of
      their patients with osteoporosis, including those from the National Osteoporosis
      Foundation, and the new fracture risk assessment tool from the World Health
      Organization. Bisphosphonates are the most commonly used treatment for
      postmenopausal osteoporosis. Although these agents are effective in preventing
      fractures and bone loss, the benefits of treatment may be limited by suboptimal
      adherence and compliance. Denosumab is a human monoclonal antibody that targets
      and inhibits RANK ligand, an essential mediator of bone resorption. In clinical
      trials in postmenopausal women with osteoporosis, denosumab 60 mg given
      subcutaneously every 6 months was well tolerated and statistically significantly
      reduced the risk of vertebral, nonvertebral, and hip fractures. The introduction
      of denosumab into clinical practice provides physicians with another option for
      the treatment of postmenopausal osteoporosis, and the twice-yearly dosing regimen
      has the potential to improve adherence.

PMID- 21084795
TI  - Acute intravenous synaptamine complex variant KB220TM "normalizes" neurological
      dysregulation in patients during protracted abstinence from alcohol and opiates
      as observed using quantitative electroencephalographic and genetic analysis for
      reward polymorphisms: part 1, pilot study with 2 case reports.
AB  - It is well established that in both food- and drug-addicted individuals, there is
      dopamine resistance due to an association with the DRD2 gene A1 allele. Evidence
      is emerging whereby the potential of utilizing a natural, nonaddicting, safe,
      putative D2 agonist may find its place in recovery from reward deficiency
      syndrome (RDS) in patients addicted to psychoactive chemicals. Utilizing
      quantitative electroencephalography (qEEG) as an imaging tool, we show the impact
      of Synaptamine Complex Variant KB220TM as a putative activator of the mesolimbic
      system. We demonstrate for the first time that its intravenous administration
      reduces or "normalizes" aberrant electrophysiological parameters of the reward
      circuitry site. For this pilot study, we report that the qEEGs of an alcoholic
      and a heroin abuser with existing abnormalities (ie, widespread theta and
      widespread alpha activity, respectively) during protracted abstinence are
      significantly normalized by the administration of 1 intravenous dose of
      Synaptamine Complex Variant KB220TM. Both patients were genotyped for a number of
      neurotransmitter reward genes to determine to what extent they carry putative
      dopaminergic risk alleles that may predispose them for alcohol or heroin
      dependence, respectively. The genes tested included the dopamine transporter
      (DAT1, locus symbol SLC6A3), dopamine D4 receptor exon 3 VNTR (DRD4), DRD2 TaqIA
      (rs1800497), COMT val158 met SNP (rs4680), monoamine oxidase A upstream VNTR
      (MAOA-uVNTR), and serotonin transporter-linked polymorphic region (5HTTLPR, locus
      symbol SLC6A4). We emphasize that these are case studies, and it would be
      unlikely for all individuals to carry all putative risk alleles. Based on
      previous research and our qEEG studies (parts 1 and 2 of this study), we
      cautiously suggest that long-term activation of dopaminergic receptors (ie, DRD2
      receptors) will result in their proliferation and lead to enhanced "dopamine
      sensitivity" and an increased sense of happiness, particularly in carriers of the
      DRD2 A1 allele. This is supported by a clinical trial on Synaptamine Complex
      Variant KB220TM using intravenous administration in > 600 alcoholic patients,
      resulting in significant reductions in RDS behaviors. It is also confirmed by the
      expanded oral study on Synaptose Complex KB220ZTM, published as part 2 of this
      study. Future studies must await both functional magnetic resonance imaging and
      positron emission tomography scanning to determine the acute and chronic effects
      of oral KB220TM on numbers of D2 receptors and direct interaction at the nucleus
      accumbens. Confirmation of these results in large, population-based, case
      controlled experiments is necessary. These studies would provide important
      information that could ultimately lead to significant improvement in recovery for
      those with RDS and dopamine deficiency as a result of a multiple neurotransmitter
      signal transduction breakdown in the brain reward cascade.

PMID- 21084797
TI  - Review of the ESPRIT study: aspirin plus dipyridamole versus aspirin alone for
      prevention of vascular events after a noncardioembolic, mild-to-moderate ischemic
      stroke or transient ischemic attack.

PMID- 21084796
TI  - Overcoming qEEG abnormalities and reward gene deficits during protracted
      abstinence in male psychostimulant and polydrug abusers utilizing putative
      dopamine D2 agonist therapy: part 2.
AB  - BACKGROUND: It is well established that in both food- and drug-addicted
      individuals there is "dopamine resistance" associated with the DRD2 gene A1
      allele. Based on earlier studies, evidence is emerging wherein the potential of
      utilizing a natural, nonaddicting, safe, putative D2 agonist may play a
      significant role in the recovery of individuals with reward deficiency syndrome,
      including those addicted to psychoactive chemicals. FINDINGS: Positive outcomes
      demonstrated by quantitative electroencephalographic (qEEG) imaging in a
      randomized, triple-blind, placebo-controlled, crossover study involving oral
      Synaptose Complex KB220ZTM showed an increase of alpha waves and low beta wave
      activity in the parietal brain region. Using t statistics, significant
      differences observed between placebo and Synaptose Complex KB220ZTM consistently
      occurred in the frontal regions after week 1 and then again after week 2 of
      analyses (P = 0.03). This is the first report to demonstrate involvement of the
      prefrontal cortex in the qEEG response to a natural putative D2 agonist
      (Synaptose Complex KB220ZTM), especially evident in dopamine D2 A1 allele
      subjects. Independently, we have further supported this finding with an
      additional study of 3 serious polydrug abusers undergoing protracted abstinence
      who carried the DRD2 A1 allele. Significant qEEG differences were found between
      those who received 1 dose of placebo compared with those who were administered
      Synaptose Complex KB220ZTM. Synaptose Complex KB220ZTM induced positive
      regulation of the dysregulated electrical activity of the brain in these addicts.
      The results are indicative of a phase change from low amplitude or low power in
      the brain to a more regulated state by increasing an average of 6.169 mV(2)
      across the prefrontal cortical region. In the first experiment we found that
      while 50% of the subjects carried the DRD2 A1 allele, 100% carried >= 1 risk
      allele. Specifically, based on the proposed addiction risk score for these 14
      subjects, 72% had moderate-to-severe addiction risk. Similar findings were
      obtained by repeating the experiment in 3 additional currently abstinent polydrug
      abusers carrying the DRD2 A1 allele. CONCLUSION: This seminal work will provide
      important information that may ultimately lead to significant improvement in the
      recovery of individuals with psychostimulant and polydrug abuse problems,
      specifically those with genetically induced dopamine deficiency. Based on this
      small sample size, we are proposing that with necessary large populations
      supporting these initial results, and possibly even additional candidate genes
      and single nucleotide polymorphisms, we may eventually have the clinical ability
      to classify severity according to genotype and possession of risk alleles, along
      with offering a safe, nonaddicting, natural dopaminergic receptor agonist that
      potentially upregulates instead of downregulates dopaminergic receptors,
      preferably the D2 subtype.

PMID- 21084798
TI  - Puzzles in practice. Xanthogranulomatous pyelonephritis (XGP).

PMID- 21084799
TI  - [RNA interference for cancer therapies].
AB  - RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in
      mammalian cells and its discovery has lead to its wide application as a powerful
      tool in post-genomic research. Recently, short interfering RNA (siRNA), which
      induces RNAi, has been experimentally introduced as a cancer therapy and is
      expected to be developed as a nucleic acid-based medicine. Selection of
      appropriate gene targets is an important parameter in the potential success of
      siRNA cancer therapies. Candidate targets include genes associated with cell
      proliferation, metastasis, angiogenesis, and drug resistance. Importantly,
      silencing of such genes must not affect the functions of normal cells.
      Development of suitable drug delivery systems (DDSs) is also an important issue.
      Numerous methods to transfect siRNAs into cells have been developed, and the use
      of non-viral DDSs is preferred because it offers greater safety for clinical
      application than does the use of viral DDSs. In this article, we briefly review
      the mechanism of RNAi and non-viral DDSs. Next, we discuss some of the most
      recent findings concerning the administration of siRNAs against polo-like kinase
      1 (PLK-1), which regulates the mitotic process in mammalian cells. Finally,
      several current clinical trials of RNAi therapies against cancers are discussed.
      Results of current studies and clinical trials demonstrate that manipulation of
      the RNAi mechanism by use of targeted siRNA offers a novel and attractive
      therapeutic option against cancer.

PMID- 21084800
TI  - [DNA methylation and cancer metastasis].
AB  - Cancer cells acquire metastatic phenotypes by accumulating genetic and epigenetic
      abnormalities. DNA methylation is involved in epigenetic regulation of gene
      transcription and frequently altered with carcinogenesis. Two modes of aberrant
      DNA methylation, promoter hypermethylation and global hypomethylation, play a
      role in cancer metastasis with different mechanisms. Here, we discuss how the
      aberrant DNA methylation contributes to acquisition of metastatic phenotypes in
      cancer and review the recent trials for molecular diagnosis of cancer metastasis
      using methylation markers.

PMID- 21084801
TI  - [Metastasis and hypoxia-inducible factor].
AB  - Cancer cells undergo distinct responses including anaerobic metabolism and
      angiogenesis, to cope with their hypoxic environment. These responses are
      achieved at least partly by the action of transcriptional factors, which are
      called hypoxiainducible factors (HIFs). HIFs consist of a constitutively
      expressed subunit of HIF-1beta and an oxygen-regulated subunit of HIF-1alpha (or
      HIF-2alpha and HIF-3alpha). In hypoxia, an HIF-1alpha subunit becomes stable and
      regulates the expression of target genes. Clinical and experimental evidence
      suggest that altered gene expression induced by HIFs in response to the hypoxic
      microenvironment is a contributing factor to increasing metastatic efficiency.
      Diffusion-limited hypoxia, a consequence of tumor cells that are distant from the
      vascular supply, was the original concept behind hypoxia in tumors, and it was
      suggested that perfusion-limited hypoxia(acute or fluctuating hypoxia), due to
      fluctuations in blood flow, might play an important role in tumors. However, the
      effects of fluctuating hypoxia on gene expression induced by HIFs have yet to be
      addressed. In the present review, we focus on a number of genes that have been
      implicated in the metastatic process, and have been found to be hypoxia
      responsive.

PMID- 21084802
TI  - [Chemokine and chemokine receptor related to cancer metastasis].
AB  - The relationship has become clear between the expression of chemokine/chemokine
      receptors on cancer cells and the invasion, metastasis and peritoneal
      dissemination. Many cancer cells express chemokine receptors which are not
      expressed on the surface of normal tissues. Recently, it has been reported that
      overexpression of CXCR4/CXCL12 is related with metastasis to lung, liver, lymph
      nodes and bone marrow, while the overexpression of CCR7/CCL21 is mainly related
      with lymph node metastasis. We performed a comparative analysis of differential
      gene expressions related to chemokines/chemokine receptors, and cytokines in
      established gastric cancer cell lines by cDNA microarray. Upregulated chemokine
      genes were CCL21, CCL5, CXCL14, CCL2, CXCL1, CXCL8, CXCL7 and CXCL12, which the
      downregulated chemokines genes were MIP-1alpha and TECK. The upregulated gene of
      chemokine receptors was CCR-6. In the cancer microenvironment, cancer cells
      readily formed edematous and inflammatory conditions, easily metastasizing to
      other organs with the suppression of dendritic cells. The chemokines/chemokine
      receptors will hopefully become the new targets for cancer therapies for the
      regulation of metastasis.

PMID- 21084803
TI  - [Extracellular matrix--regulation of cancer invasion and metastasis].
AB  - Cancer cell invasion comprises steps in the destruction of the basement membrane
      and migration of cells into the connective tissue. These cells further migrate
      into lymph ducts and small vessels to reach metastasis. The extracellular matrix
      (ECM) provides a microenvironment for cells, and its destruction is associated
      with cancer cell invasion. Among matrix metalloproteinases (MMPs), both MMP-2 and
      9 digest type IV collagen, a major component of the basement membrane, and MMP
      14/MT1-MMP, a membrane-type MMP, activates MMP-2. Thus, these MMPs play a central
      role in cancer cell invasion. MMPs also cleave latent forms of growth factors and
      signaling molecules, releasing and activating them, which influence neo
      vascularization and cancer apoptosis. Like proteins, carbohydrates are known to
      be involved in cancer invasion. Hyaluronan is known to both stimulate and inhibit
      cancer invasion, depending on its molecular size. Heparanase, which digests
      heparan sulfate, is known to facilitate cancer invasion and metastasis. In
      summary, ECM provides a microenvironment that regulates cell behavior and its
      structure altered by MMPs affects cancer cell invasion.

PMID- 21084804
TI  - [Exploration of metastasis-related proteins based upon proteomic analysis].
AB  - Omics analysis is defined as a comprehensive analysis of various biological
      aspects from gene sequence to metabolite pattern via protein expression, and it
      might revolutionarily alter the design of scientific experiments as well as the
      process of biological investigation. Furthermore, omics technologies allow the
      generation of huge amounts of data at high-throughput. Particularly, proteomics
      is one of the omics technologies, which is a comprehensive analysis of protein,
      and it is hoped that proteomics accelerates translational research in the field
      of malignant neoplasm. Given the present status of proteomics technologies, we
      performed differential analysis between two categories such as a metastasis
      positive group and a negative group using the clinical materials of a single kind
      of malignant neoplasm, and detected various kinds of protein molecules associated
      with metastasis. However, we could not obtain any evidence that these molecules
      were directly related with metastasis. The close relationship between clinical
      doctors, molecular pathologists and technical experts concerning proteomics is
      essential, because an experimental design, which they would generate, is
      extremely important for the detection of the targeted molecules. Additionally, in
      this paper some recent reports concerning the exploration of metastasis-related
      molecules using proteomic technology proteomics are introduced.

PMID- 21084805
TI  - [Clinical characteristics of cases showing complete regression of the primary
      tumor after S-1 combined with cisplatin administered as neoadjuvant chemotherapy
      in advanced gastric carcinoma].
AB  - Although neoadjuvant chemotherapy has been recognized as an important option to
      improve the clinical outcome of patients with advanced gastric carcinoma, the
      precise histological effects of neoadjuvant chemotherapy on the primary and
      metastatic foci have not well been documented. The aim of the present study was
      thus to evaluate histological effects of S-1-based neoadjuvant chemotherapy on
      the resected specimens of gastric carcinoma and regional lymph nodes, and
      primarily to focus on the histology of the cases showing complete regression of
      the primary cancer cells. A total of 164 patients received neoadjuvant
      chemotherapy with the combination of S-1 (80 to 120 mg/body/day for 3 weeks) and
      cisplatin (35 to 60 mg/m2 on day 8). One course of the regimen was completed in 5
      weeks and the next course was started after 2 weeks. A total of 9 patients who
      showed complete regression of the primary gastric cancer were subjects of the
      study. A total of 77 cases (46.9%) responded to the neoadjuvant chemotherapy and
      9 cases (5.5%) showed a complete regression of the primary gastric carcinoma.
      Three out of 9 cases had remnant cancer cells in the metastatic foci; 1 in the
      liver and 2 in the regional lymph nodes. Five of 9 cases were solid-type poorly
      differentiated adenocarcinoma (por1), and the incidence of responders was the
      highest in patients with por1. A total of 8 cases were alive and the mean
      postoperative survival was 612+/-192 days. One patient died 518 days after
      gastrectomy associated with hepatic resection. S-1-based neoadjuvant chemotherapy
      has significant histological effects on gastric carcinoma and metastatic foci,
      which may further improve long-term clinical outcome in patients with advanced
      gastric carcinoma.

PMID- 21084806
TI  - [Cost-effectiveness analysis comparing carboplatin and weekly paclitaxel with
      cisplatin and docetaxel in the treatment of advanced non-small cell lung
      carcinoma].
AB  - Carboplatin plus weekly paclitaxel (CBDCA/wPTX) and cisplatin plus docetaxel
      (CDDP/DTX) are the standard regimens used in the first-line treatment of advanced
      non-small cell lung carcinoma (NSCLC), with no significant difference in efficacy
      between the two. However, because there has been no study of the cost
      effectiveness of CBDCA/wPTX versus CDDP/DTX to data, we compared these two
      regimens in the present study. Expected costs were calculated based on data from
      patients with Stage III b/IV NSCLC who were treated with either CBDCA/wPTX or
      CDDP/DTX in the Nippon Medical School Hospital. Efficacy (1-year survival rate)
      was determined by pooled analysis of studies extracted from the database. The
      cost-effectiveness ratio was calculated from expected costs and 1-year survival
      rates for both the CBDCA/wPTX and CDDP/DTX regimens. The expected costs per
      patient of the CBDCA/wPTX and CDDP/DTX regimens were Y2, 847, 514 and Y3, 513,
      195, respectively, with 1-year survival rates of 38.6% and 42.5%, respectively.
      Thus, the cost-effectiveness ratio for the CBDCA/wPTX and CDDP/DTX regimens is
      Y6, 750, 863 and Y8, 329, 054, respectively. These findings clearly suggest that,
      CBDCA/wPTX is a more cost-effective regimen than CDDP/DTX.

PMID- 21084807
TI  - [A retrospective survey on allergic reactions by oxaliplatin].
AB  - Fifty-six patients treated with oxaliplatin were examined in order to clarify the
      factors that influence the appearance of allergic reactions by oxaliplatin at
      Kyoto City Hospital between January 2009 and December 2009, retrospectively. The
      number of patients in allergic and non-allergic group was 10 and 46,
      respectively. Patients' characteristics, the presence of hepatic metastasis,
      hepatic failure and kidney failure, albumin and white blood cell counts were
      compared in both groups. In the allergic group, the rate of hepatic metastasis
      was significantly higher than that in the non-allergic group (p=0.011). In
      conclusion, hepatic metastasis was suggested to be a factor that causes allergic
      reactions after administration of oxaliplatin.

PMID- 21084808
TI  - [Prediction of gemcitabine treatment discontinuation based on platelet count
      before first administration].
AB  - Decrease in white blood cell (WBC), neutrophil or platelet (PLT) count due to
      treatment with gemcitabine (GEM) is a dose-limited factor (DLF). Even for cases
      that satisfy the standard criteria for initiation of GEM therapy, the scheduled
      therapy is reportedly occasionally discontinued because of decreased PLT or WBC
      count. Here, a retrospective study was made to predict the factor causing
      discontinuation of GEM treatment before its first administration. The results
      showed that PLT count immediately before the first administration was
      significantly less in the unfinished administration group than in the finished
      group. It was also demonstrated that a PLT count less than 16*10/4 mL before the
      first administration of GEM was the significant risk factor leading to
      discontinuation of GEM treatment. Thus, it was suggested that this result would
      be available as the dose reduction standard to determine the first dose of GEM
      treatment.

PMID- 21084809
TI  - [Results of chemotherapy in head and neck cancer patients with residual or
      recurrent tumors after initial treatment].
AB  - A study of S-1 chemotherapy treatment of patients with head and neck cancer was
      conducted in 26 patients with residual or recurrent tumors after the initial
      treatment, i. e., chemoradiotherapy, radiotherapy and operation. The treatment
      courses consisted of oral administration of S-1 at a dose of 80 to 120 mg/day
      depending on the body surface area, for 14 consecutive days followed by a 7-day
      rest period. The response rate in all patients was 34.6%(9/26). In patients with
      recurrent tumors, the response rate was 11.1% (1/9). Patients with residual
      tumors after the initial treatment had a response rate of 47.0% (8/17). The
      median survival time was 490 days. Moreover, we studied the maintenance of QOL
      (quality of life) in 15 cases whose deaths were caused by their tumors. The
      maintenance duration of QOL was 162 to 1,742 days (median 330 days). The mean QOL
      maintenance rate, i. e., the average period of extended life with stable disease
      compared to the period from the eternity time of S -1 treatment until patient
      death, was 81.1% (36.4-98.7%). S-1 is a safe anticancer drug with fewer side
      effects than other chemotherapies. S-1 did not cause any serious adverse events
      in the patients enrolled in this study. Therefore, S-1 appears to be useful for
      the treatment of patients with head and neck cancer, and it is particularly
      useful for improving the QOL of patients.

PMID- 21084810
TI  - [Effectiveness and safety of chemoradiation in a community-based population of
      patients with esophageal cancer].
AB  - BACKGROUND: In Japan, esophagectomy with three-field lymphadenectomy is the
      standard therapy for resectable esophageal cancer. However, its outcome is
      considered unsatisfactory because the 5-year survival rate is less than 50%.
      Chemoradiotherapy (CRT) is the standard therapy for unresectable esophageal
      cancer and could also be considered as an option for resectable esophageal
      cancer. We retrospectively determined the efficacy and safety of CRT for patients
      with esophageal cancer. METHODS: The study population comprised patients with
      esophageal cancer who had been treated with CRT between April 2004 and October
      2009 in our institute. Acute and late toxicity was assessed with NCI-CTC and
      RTOG/EORTC late radiation morbidity scoring scheme, respectively. Survival time
      was calculated using Kaplan-Meier methods. RESULTS: We enrolled 29 consecutive
      patients and classified them on the basis of clinical staging: stage I, 4
      patients; stage II/III, 11 patients; and stage IV, 14 patients. Complete response
      was achieved in 37.9% and 45.5% of the total study population and the stage
      II/III group, respectively. The median survival time in these groups was 12.1
      months and 15 months, respectively. Grade 3/4 acute toxicities were observed in
      62.1% of the patients. Grade 3/4 late toxicities were observed in 12% of the
      patients. The first failure after CRT was almost locoregional. CONCLUSION: CRT
      appears to be an effective therapy for esophageal cancer; however, its outcome is
      not satisfactory. Therefore, it is necessary to evaluate the role of salvage
      surgery after CRT and new chemotherapeutic agents.

PMID- 21084811
TI  - [Effects of irinotecan and 5-FU combination therapy in gastric cancer--is
      combination therapy synergic?].
AB  - The response rate of Irinotecan for gastric cancer is reported to be 18. 4%. The
      rate is improved by combination with 5-FU. However, it remains unclear whether or
      not the effect of the two drugs is synergy or antagonistic. The purpose of this
      study is to clarify whether the effect of Irinotecan and 5-FU in gastric cancer
      is synergy or antagonistic. We performed study using 13 specimens removed
      surgically and 2 specimen collected from ascites. We performed the Collagen Gel
      Droplet Embedded Culture Drug Sensitivity Test (CD-DST) with 3 assumptions. In
      the first assumption, we let 5-FU come in contact with a tumor at a level of 1
      mg/mL for 24 hours. The second assumption was SN-38 at a level of 30 mg/mL for 24
      hours and the 3rd assumption was SN-38 at a level of 30 mg/mL and 5-FU at a level
      of 1 mg/mL for 24 hours. If the combination index was more than 1, the
      combination therapy was judged as synergic; if less than 1, it was considered
      antagonistic. RESULTS: The inhibition rate of combination therapy was
      significantly higher than that of monotherapy. The inhibition rate of combination
      therapy was significantly correlate with that of monotherapy (Irinotecan;
      r=0.704, p=0.003, 5-FU; r=0.746, p=0.001). The combination index was antagonistic
      in only 6 of 15 cases. However, it was synergic in all well-differentiated
      adenocarcinomas (4/4). DISCUSSION: We conclude that combination therapy is
      antagonistic in most cases of gastric cancer in vitro. However, it may be
      synergic in well-differentiated adenocarcinomas.

PMID- 21084812
TI  - [The incidence of gastrointestinal bleeding, thromboembolic events, and
      gastrointestinal perforation in metastatic or unresectable gastric cancer during
      chemotherapy].
AB  - The incidence of gastrointestinal bleeding, thromboembolic events and
      gastrointestinal perforation during chemotherapy with metastatic or unresectable
      gastric cancer has been unknown. To clarify the incidence of these events, we
      reviewed the clinical records of our hospital. PATIENTS AND METHODS: We
      investigated metastatic or unresectable gastric cancer patients who received
      chemotherapy during January 2002 to December 2006. Grade>=3 (CTCAE v3.0) adverse
      events from the first day of chemotherapy to 1 month after the last day of
      chemotherapy were investigated. RESULTS: A total of 292 patients received
      chemotherapy. Patient characteristics were as follows: median age 63.5 years
      (range, 28 to 87); performance status 0/1/2/3: 129/129/31/3; male: female,
      206:86, histopathological type intestinal/diffuse/unclassified
      adenocarcinoma/others: 91/139/58/4. We found the incidence of Grade>=3
      gastrointestinal bleeding in 7 patients (2.4%), thromboembolic events in 5
      patients (1.7%) and gastrointestinal perforation in 3 patients (1.0%).
      Thromboembolic events in patients under 55 years of age were associated with a
      higher incidence (p=0. 0046). CONCLUSION: The incidence was not so high as
      expected. We should be aware of the frequency of these toxicities in the
      treatment of gastric cancer.

PMID- 21084813
TI  - [Risk associated with severe hematological toxicity in patients with advanced or
      recurrent colonic cancer receiving combination chemotherapy of S-1 and irinotecan
      hydrochloride].
AB  - The aim of this study was to analyze the risk factors for grade 3 to 4
      hematological toxicity after primary chemotherapy (Tegafur, gimeracil, oteracil
      potassium (S-1)/irinotecan hydrochloride (CPT-11)) in 87 (56 male, 31 female;
      median age 66.1 years) patients with unresectable or recurrent colonic cancer
      between April 2005 and May 2009, and to prepare a risk classes (low-risk,
      intermediate-risk or high-risk groups). The rate of grade 3 to 4 hematological
      toxicity was 16.1%. At multivariate analysis, risk factors for grade 3 to 4
      hematological toxicity were baseline WBC, Cr, female (p<0.05). The toxicity index
      (TI) consisted of risk factors and regression coefficient. We were stratified
      patients into three groups according to TI that was calculated for each patient.
      The group with high value was found to include patients with grade 3 to 4
      hematological toxicity with a significantly higher frequency than the group with
      low value (4.2% vs 57.1%, p=0.004). This risk classes could be useful to identify
      patients at high risk for chemotherapy-induced grade 3 to 4 hematological
      toxicity.

PMID- 21084814
TI  - [Four resected cases with basaloid carcinoma of esophagus--comparison of 5-FU
      related enzymes (thymidylate synthase (TS), dihydropyrimidine dehydrogenase
      (DPD), orotate phosphoribosyl transferase (OPRT)) between basaloid carcinoma and
      squamous cell carcinoma].
AB  - We reported herein four resected cases with basaloid carcinoma of the esophagus
      and measured the activity of 5-FU related enzymes (TS, DPD, OPRT) in cancer
      tissue. These activities compared with those in squamous cell carcinoma. Only one
      case was diagnosed as basaloid carcinoma by preoperative biopsy specimen at
      endoscopic examination. The esophagectomy was performed thoracoscopically in all
      cases, and the abdominal procedure was done with the laparoscopic approach in two
      cases. Anastomotic leakage occurred in one case. No case had lymph node
      metastasis. On the other hand, a lymphatic invasion was detected in one case, and
      venous invasion in two, respectively. Two cases had mediastinal lymph node
      recurrence. DPD activity and OPRT activity showed no difference between squamous
      cell carcinoma and basaloid carcinoma. On the other hand, the TS activity was
      significantly higher in basaloid carcinoma. From the standpoint of 5-FU-related
      enzyme activities, basaloid carcinoma possibly has more resistance to 5-FU than
      squamous cell carcinoma.

PMID- 21084815
TI  - [A case of non-small cell lung cancer responding to S-1 over a year].
AB  - A 71-year-old woman was admitted to our hospital, because of an abnormality on
      her chest radiograph findings. After extensive examination, she was diagnosed
      with primary lung adenocarcinoma (cT4N2M1, stage IV). She was treated by
      carboplatin+gemcitabine, gefitinib and docetaxel and the responses were stable
      disease in any treatment. As the fourth-line treatment, she received oral
      chemotherapy using S-1 at 100 mg/day (80 mg/m2 day) for 28 days, followed by
      withdrawal for 14 days. Tumor size was reduced 29.2% after 1 course, 62.5% after
      5 courses and 83.3% after 10 courses (14 months). Hematologic and non-hematologic
      toxicities were mild with the S-1 administration. We experienced a case of
      continuation of tumor shrinkage over a year without serious adverse events by S-1
      treatment. Therefore, oral administration of S-1 could be useful for the
      treatment of recurrent non-small cell lung cancer over a long time.

PMID- 21084816
TI  - [A case of complete resection of a squamous cell lung cancer invading diaphragm
      after neoadjuvant chemotherapy of nedaplatin and irinotecan].
AB  - The treatment for squamous cell lung cancer has remained unclear, while that for
      lung cancer according to each pathology type has advanced. This is a case of
      complete response of a squamous cell lung cancer invading the diaphragm which
      could be resected completely after neoadjuvant chemotherapy of nedaplatin (CDGP)
      and irinotecan (CPT-11). CDGP and CPT-11 might be effective for squamous cell
      lung cancer.

PMID- 21084817
TI  - [Peritoneal disseminated recurrence after total gastrectomy for perforated
      gastric malignant lymphoma--a case report].
AB  - We reported a case of peritoneal disseminated recurrence after total gastrectomy
      for perforated gastric malignant lymphoma. A 73-year-old man underwent total
      gastrectomy for perforated gastric diffuse large B cell lymphoma on day 5 of
      RCHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and
      prednisolone) chemotherapy. He has rejected chemotherapy and received no
      additional treatment after gastrectomy. Computer tomography 13 months after
      surgery revealed peritoneal dissemination and abdominal lymph node metastasis. R
      CHOP chemotherapy was performed, and after 4 courses of chemotherapy, peritoneal
      dissemination and metastatic abdominal lymph nodes disappeared. Chemotherapy was
      discontinued for a time, however, the tumors relapsed 2 months after stopping
      chemotherapy. He underwent chemotherapy with etoposide, but died of tumor
      progression 21 months after gastrectomy.

PMID- 21084818
TI  - [A case of recurrent invasive thymic cancer showing a stable disease to
      carboplatin plus paclitaxel].
AB  - A 56-year-old man was admitted to our hospital because of increasing chest
      discomfort and abnormal chest shadow. Computed tomography (CT) of the chest
      revealed an anterior mediastinal mass, pleural dissemination and lung metastasis.
      Percutaneus needle biopsy guided by CT showed that the mass was advanced thymic
      cancer (stage IV b according to the classification proposed by Masaoka). After
      failure of combination chemotherapy of cisplatin, vincristine, doxorubicin and
      etoposide (CODE), he received 4 cycles of carboplatin plus paclitaxel and then
      achieved confirmed stable disease. In terms of toxicity profile, grade 4 anemia,
      grade 2 leucopenia and neutropenia were observed, and particularly non-severe
      toxicity was not observed in terms of non-hematologic toxicity. Carboplatin plus
      paclitaxel can be an active agent against pretreated thymic cancer.

PMID- 21084819
TI  - [Two cases of HER2-positive advanced or metastatic breast cancer, responding to
      lapatinib and capecitabine].
AB  - The first patient was a 59-year-old woman who was diagnosed with invasive
      scirrhous carcinoma. The tumor was estrogen receptor (ER)-positive, progesterone
      receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)
      positive. The patient was treated with adjuvant chemotherapy and endocrine
      therapy after surgery. Liver metastases developed 5 years after surgery. She was
      treated with trastuzumab combined with vinorelbine, paclitaxel, or docetaxel. The
      liver metastases increased in size, 9 years after surgery, and she was treated
      with lapatinib and capecitabine. The efficacy of chemotherapy was judged as a
      partial response. The second patient was a 74-year-old woman who was diagnosed
      with invasive ductal carcinoma in 2005. The tumor was ER-negative, PgR-positive,
      and HER2-positive; she was treated with trastuzumab and paclitaxel. She developed
      dyspnea in January 2010. Chest radiograph showed increased lung metastases and
      left pleural effusion; she was treated with lapatinib and capecitabine. Lung
      metastases decreased and left pleural effusion disappeared after the first cycle
      of chemotherapy. The efficacy of chemotherapy was judged as a partial response.

PMID- 21084820
TI  - [Five cases of advanced gastroesophageal junction adenocarcinoma successfully
      treated with chemoradiotherapy followed by curative resection].
AB  - We reviewed five patients with advanced gastroesophageal cancer who were
      successfully treated with chemoradiotherapy followed by a curative resection.
      Patients with histologically-documented adenocarcinoma of the gastroesophageal
      junction were eligible. Direct tumor extension into the stomach (cT3 or cT4), and
      involvement of lymph nodes were observed. The patients stopped receiving orally
      administered carcinostatic drugs due to digestive stenosis or tumor bleeding.
      They received 25 mg/m2 of cisplatin and 60 mg/m2 of paclitaxel once a week on
      days 1, 8, 15 and 22. Radiation was administered concurrently at a total dose of
      45 Gy in 1.8 Gy fractions for over 25 treatments. Effectiveness of the therapy
      was evaluated 4 weeks after the chemoradiotherapy. All patients with clinical
      partial responses underwent gastrectomy (n=4) or esophagogastrectomy (n=1).
      Curative resection was performed in 5 patients (resection A/B 4/1), and no
      patient suffered from major postoperative complications. Four patients were
      downstaged according to the pathological findings. The histologically effective
      responses of all patients were Grade 2. The obvious chemotherapeutic efficacy of
      the present regimen suggested that it may be a good treatment option for advanced
      gastroesophageal cancers. Further studies including randomized controlled trials
      are needed to evaluate the significance of preoperative chemoradiotherapy.

PMID- 21084821
TI  - [Complete histological response in advanced gastric cancer with Virchow's node
      metastasis after chemotherapy including S-1/CDDP--report of a case].
AB  - A 63-year-old male complaining of jaundice was examined and diagnosed with
      advanced gastric cancer (type 3, tub 2, cT3, cN3, cH0, cM1, cStage IV), and
      obstructive jaundice due to lymph node metastasis. Since curative surgery was
      deemed not possible, we started chemotherapy with S-1+CDDP. S-1 (120 mg/day) was
      administered orally for 21 days, followed by CDDP (60 mg/m2) div on day 8. After
      the 9th course, a significant tumor reduction was obtained. Total gastrectomy and
      lymph node resection (D1) were performed. The histological diagnosis revealed
      complete disappearance of cancer cells in both the main tumor and lymph nodes.
      Herein we report this rare case with a view of the literature.

PMID- 21084822
TI  - [Analysis of four patients with advanced gastric cancer undergoing gastrectomy
      after pre-operative combination chemotherapy using docetaxel, cisplatin and S-1].
AB  - We analyzed the clinical efficacy of pre-operative combination chemotherapy using
      docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were
      enrolled and staging laparoscopy was performed. Patients received intravenous
      docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day
      1-14 every 4 weeks. Two patients received two courses of chemotherapy and two
      patients received three courses of chemotherapy. Neutropenia of more than grade 3
      was found in 3 cases. All cases were PR on preoperative imaging. Curative
      operation was performed on three cases. Histological anti-tumor effect was judged
      to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all
      patients received S-1-based adjuvant chemotherapy. The combination chemotherapy
      using docetaxel, cisplatin and S-1 plus operation was a candidate for the
      standard treatment strategy for advanced gastric cancer.

PMID- 21084823
TI  - [Complete response achieved in a case of gastric gastrointestinal stromal tumor
      by administration of imatinib mesilate with concurrent relatively high-dose
      steroid therapy to control side effects].
AB  - We present a 53-year-old man who underwent proximal gastrectomy for gastric
      gastrointestinal stromal tumor (GIST) in August 2005. Imatinib mesilate
      (imatinib) 400 mg/day was started in February 2006 for left adrenal metastasis.
      Tumor size markedly decreased by April 2006, but medication had to be
      discontinued due to a pruritic rash. A distal pancreatectomy, splenectomy, and
      left adrenectomy were performed in August for recurrent adrenal metastases.
      Imatinib 200 mg/day started postoperatively was discontinued immediately due to
      fever and pruritus. Local recurrence with peritoneal dissemination was found in
      February 2007. Imatinib 100 mg/day with prednisolone (PDL) 5 mg/day was
      discontinued in two days due to pruritic dermatitis. Imatinib 200 mg/day with PDL
      40 mg/day was restarted in April due to an increase in tumor size. Treatment
      continued without obvious side effects, and PDL dosage was tapered to 10 mg/day.
      The tumor was no longer visible on CT in May 2008, and complete response is being
      maintained as of August 2009.

PMID- 21084824
TI  - [Two cases of colorectal cancer presenting with periodic, transient elevation of
      serum iron after chemotherapy including irinotecan].
AB  - It is known that the serum iron level shows a transient elevation after
      chemotherapy in some cases; however, the cause of this phenomenon has not been
      clearly described. We report two cases of colorectal cancer whose serum iron
      level demonstrated recurrent elevation after administration of irinotecan as a
      second-line chemotherapy. The transferrin saturation rate showed marked elevation
      together with serum iron. This fact indicates that the release of non-transferrin
      bound iron (NTBI) occurs and then, NTBI binds with transferrin immediately
      thereafter. Additionally, elevation of indirect bilirubin in case 1, and mild
      anemia in case 2 were observed after every course of chemotherapy. All these
      phenomena were synchronized with the fluctuation of the serum iron level. These
      observations suggest that the transient elevation of the serum iron was related
      with the release of the NTBI from red blood cells after chemotherapy including
      irinotecan.

PMID- 21084825
TI  - [Two cases of colorectal cancer patients with poor performance status who had
      unresectable liver metastasis effectively treated by cetuximab].
AB  - We reported two cases of colorectal cancer patients with EGFR-positive
      unresectable synchronous liver metastasis effectively treated by cetuximab after
      the progression of the prior chemotherapy. Case 1: A 49-year-old female with
      unresectable synchronous liver metastasis from colon cancer received cetuximab
      monotherapy as fifth-line therapy. Then, abdominal CT showed shrinkage of the
      liver metastasis (PR) and the performance status was improved from 3 to 0 as
      upper abdominal pain reduced. Case 2: A 67-year-old female with unresectable
      liver metastasis from colon cancer received cetuximab with CPT-11 combined
      therapy as fourth-line therapy. After that, liver metastasis also decreased (PR),
      and upper abdominal pain and PS were improved from 2 to 0. These two cases of
      KRAS status on cancer tissue also showed wild-type, and in these cases cetuximab
      proved effective.

PMID- 21084826
TI  - [A case of recurrent colon cancer with angina pectoris and interstitial pneumonia
      during cetuximab therapy with death by carcinomatous lymphangiosis].
AB  - The case was a man in his 60s with no past history of heart and lung. Chest
      tightness was felt during the first course of cetuximab therapy for recurrent
      colon cancer. He was diagnosed as having vasospastic angina, and administration
      of vasodilatation agents was done. After the therapy, no chest pain attack was
      seen. Chemotherapy was continued. After 3 courses, fever elevation, chest
      tightness and dyspnea were seen. Chest X-ray and CT revealed diffuse interstitial
      pneumonia in bilateral lung. Although steroid pulse therapy and intensive therapy
      with mandatory ventilation were performed, he died of respiratory failure.
      Pathological findings of autopsy revealed remarkable metastasis of cancer cells
      to the bilateral lungs accompanied chiefly with carcinomatous lymphangiosis.
      Furthermore, acute and subacute interstitial pneumonia with diffuse alveolar
      damage were seen in the background of the lungs. Cardiopulmonary disorder as well
      as skin disorder should be considered as possible adverse events of cetuximab
      therapy.

PMID- 21084827
TI  - [A case with local recurrence of rectal cancer that responded to S-1 and PSK with
      long-term complete response].
AB  - The patient was a 65-year-old male, who underwent low anterior resection for
      rectal cancer. The pathological diagnosis showed mucinous adenocarcinoma, pSS,
      and pN0. He complained of diarrhea and melena 4 months after the surgery.
      Abdominal computed tomography and colonofiberscopy showed a local recurrence of
      rectal cancer. Because the tumor was diagnosed as unresectable, combined
      chemotherapy of S-1 (100 mg/day, per os, 4 weeks of treatment and 2 weeks of
      rest) and PSK (3 g/day, per os, the same schedule as S-1) was started. After the
      2 courses of chemotherapy, computed tomography and colonofiberscopy showed a
      complete disappearance of the tumor. The chemotherapy was continued until the 9th
      course and then stopped. Five years and 4 months since the induction of a
      complete response, the patient is still alive without disease recurrence.
      Combined chemotherapy of S-1 and PSK may be one of useful choices for recurrent
      colorectal cancer.

PMID- 21084828
TI  - [Successful treatment with cetuximab combination chemotherapy in a case of FOLFOX
      refractory rectal cancer with previously unresectable multiple liver metastases
      leading to complete resection].
AB  - Most colorectal cancer patients with liver metastases are not resectable upon
      initial diagnosis. Recently, chemotherapy improves overall survival of initially
      unresectable patients by allowing tumor downstaging and complete resection. We
      report a FOLFOX-refractory rectal cancer patient with unresectable multiple liver
      metastases, whose tumors could be downstaged and completely resected after
      initiation of FOLFIRI with cetuximab. CASE: A 41-year-old male demonstrated
      rectal cancer with unresectable multiple liver metastases. He was treated by
      FOLFOX4 therapy as first-line chemotherapy. After initiating 14 courses, he was
      treated by FOLFIRI with cetuximab because of disease progression. After
      initiation of chemotherapy, radiographic examination demonstrated remarkable
      reduction of primary rectal tumor and metastatic liver tumors. He underwent
      complete rectal tumor resection after 13 courses of chemotherapy, and metastatic
      liver tumor resection after 18 courses of chemotherapy.

PMID- 21084830
TI  - [Effect of low-dose dasatinib in an elderly patient with chronic myelogenous
      leukemia (CML)].
AB  - We experienced a case of chronic myelogenous leukemia (CML) treated successfully
      with low-dose dasatinib (20 mg/day). An 87-year-old man was diagnosed with CML in
      January 2003 and was given imatinib (200 mg/day). Although complete hematologic
      responses (CHR) were achieved, we replaced imatinib with hydroxycarbamide (HU)
      because of the renal dysfunction possibly due to imatinib. However, since the
      blood count was poorly controlled with HU, treatment with dasatinib, one of the
      second-generation tyrosine kinase inhibitors, was started at the accelerated
      phase (AP) in June 2009. Dasatinib was given in a daily dose of 20 mg, intending
      dose escalation after confirmation of its safety. White blood cells and platelets
      decreased rapidly, and after 18 days, CHR was achieved. Thereafter, daily
      dasatinib was reduced twice per week because of the cytopenia. However, the
      patient has continued CHR without developing AP for more than six months. Low
      dose dasatinib might be a useful treatment in the control of selected patients
      with CML.

PMID- 21084829
TI  - [mFOLFOX6 for treatment of anal canal cancer with disseminated carcinomatosis of
      bone marrow--a case report].
AB  - A 66-year-old man was referred to our hospital because of a two-week history off
      ever and low back pain. There was a hard anal mass on rectal examination.
      Colonoscopy and computed tomography showed anal adenocarcinoma, multiple
      metastases to lymph nodes and bones. Blood test showed severe disseminated
      intravascular coagulation (DIC). Microscopic examination of the bone marrow
      aspirate revealed disseminated carcinomatosis of the bone marrow. Systemic
      chemotherapy (mFOLFOX6) was started, then remission of DIC and shrinkage of the
      tumor were observed. Although the patient had cerebral infarction during the
      first course of chemotherapy, he received nine courses of treatment. He died six
      months later because of cerebellar hemorrhage.

PMID- 21084831
TI  - [Special diet for cancer patients with the chemotherapy-induced appetite loss
      improves the quality of life in palliative care].

PMID- 21084833
TI  - Improved postural control after dynamic balance training in older overweight
      women.
AB  - BACKGROUND AND AIMS: Many studies have reported a greater frequency of falls
      among older women than men in conditions which stress balance. Previously, we
      found an improvement in static balance in older women with an increased support
      surface area and equal load redistribution on both feet, in response to a dynamic
      balance training protocol. The aim of the present study was to examine whether
      the same training program and body composition would have effects on the postural
      control of older overweight women. METHODS: Ten healthy women (68.67 +/- 5.50
      yrs; 28.17 +/- 3.35 BMI) participated in a five-week physical activity program.
      This included dynamic balance exercises, such as heel-to-toe walking in different
      directions, putting their hands on their hips, eyes open (EO) or closed (EC),
      with a tablet on their heads, going up and down one step, and walking on a mat.
      Postural stability was assessed before and after training with an optoelectronic
      platform and a uni-pedal balance performance test. Body composition of the trunk,
      upper limbs and lower limbs was measured by bio-impedance analysis. RESULTS: The
      mean speed (MS), medial-lateral MS (MS-x), anterior-posterior MS (MS-y), sway
      path (SP) and ellipse surface area (ESA) of the pressure center was reduced after
      training in older women. However, only MS, MS-x, MS-y and SP significantly
      decreased in bipodalic conditions with EO and MS-y also with EC (p<0.05).
      Instead, in monopodalic conditions, we found a significant reduction in the ESA
      of both feet with EO and EC. These data were associated with a significant
      increase in the lean mass of lower limbs and a higher number of participants who
      improved their ability to maintain unipedal static balance. CONCLUSIONS: Our
      dynamic balance training protocol appears to be feasible, safe and repeatable for
      older overweight women and to have positive effects in improving their lateral
      and anterior-posterior postural control, mainly acting on the visual and skeletal
      muscle components of the balance control system.

PMID- 21084834
TI  - Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up
      regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle
      arrest induced by silibinin and 1,25-dihydroxyvitamin D(3).
AB  - Acute myelogenous leukemia (AML) is a disease characterized by dysregulated cell
      proliferation associated with impaired cell differentiation, and current
      treatment regimens rarely save the patient. Thus, new mechanism-based approaches
      are needed to improve prognosis of this disease. We have investigated in
      preclinical studies the potential anti-leukemia use of the plant-derived
      polyphenol Silibinin (SIL) in combination with 1,25-dihydroxyvitamin D3 (1,25D).
      Although most of the leukemic blasts ex vivo responded by differentiation to
      treatment with this combination, the reasons for the absence of SIL-1,25D synergy
      in some cases were unclear. Here we report that failure of SIL to enhance the
      action of 1,25D is likely due to the SIL-induced increase in the activity of
      differentiation-antagonizing cell components, such as ERK5. This kinase is under
      the control of Cot1/Tlp2, and inhibition of Cot1 activity by a specific
      pharmacological inhibitor 4-(3-chloro-4-fluorophenylamino)-6-(pyridin-3-yl
      methylamino-3-cyano-[1-7]-naphthyridine, or by Cot1 siRNA, increases the
      differentiation by SIL/1,25D combinations. Conversely, over-expression of a Cot1
      construct increases the cellular levels of P-ERK5, and SIL/1,25D-induced
      differentiation and cell cycle arrest are diminished. It appears that reduction
      in ERK5 activity by inhibition of Cot1 allows SIL to augment the expression of
      1,25D-induced differentiation promoting factors and cell cycle regulators such as
      p27 (Kip1) , which leads to cell cycle arrest. This study shows that in some cell
      contexts SIL/1,25D can promote expression of both differentiation-promoting and
      differentiation-inhibiting genes, and that the latter can be neutralized by a
      highly specific pharmacological inhibitor, suggesting a potential for
      supplementing treatment of AML with this combination of agents.

PMID- 21084835
TI  - Dual association by TFAP2A during activation of the p21cip/CDKN1A promoter.
AB  - The cyclin-dependent kinase inhibitor p21cip/CDKN1A is induced to promote growth
      arrest in response to a variety of stimuli in normal cells and loss of correct
      regulation of this gene is frequently observed in cancer. In particular, the
      upregulation of CDKN1A by p53 is considered to be a central mechanism of tumour
      suppression. Other transcription factors with tumour suppressor activity can also
      regulate CDKN1A, including the developmentally regulated factor, TFAP2A. Here we
      identify a novel AP-2 binding site within the proximal promoter of the CDKN1A
      gene and show this is required for optimal, p53-independent expression of
      p21cip/CDKN1A. We further describe a non-tumourgenic breast epithelial cell line
      model to study the role of endogenous TFAP2A and p53 in the control of drug
      induced p21cip expression using ChIP. Maximal expression of CDKN1A requires
      TFAP2A which binds to two regions of the promoter: the proximal region where the
      AP-2 site lies and upstream near the major p53 binding site. The pattern of
      binding alters with time post-induction, with the proximal, p53-independent site
      becoming more important at later stages of p21cip induction. This pattern of
      promoter interaction by TFAP2A is distinct from that seen for the TFAP2C family
      member which represses CDKN1A expression.

PMID- 21084836
TI  - STAT1 interacts directly with cyclin D1/Cdk4 and mediates cell cycle arrest.
AB  - In response to IFN-gamma, the latent cytoplasmic STAT1 protein is tyrosine
      phosphorylated and translocates to the nucleus where it transactivates STAT1
      responsive genes. We now present data that shows that STAT1 has additional non
      transcriptional functions. We first demonstrate that STAT1 can interact directly
      with the G1 cell cycle regulatory cyclin D1 and CDK4 proteins, suggesting a role
      for STAT1 in G1 cell cycle regulation. Acute IFN-gamma treatment dramatically
      reduced cyclin D1 protein expression and the interaction of STAT1 with cyclin D1.
      The IFN-gamma-induced reduction in cyclin D1 was dependent on the proteasome
      pathway. Interestingly, the STAT1 serine 727 phosphorylation site and not the
      STAT1 tyrosine 701 site is required for cyclin D1-dependent proteosomal
      degradation. Furthermore, IFN-gamma-STAT1 cyclin D1 reduction correlated with
      decreased amount of p-Rb Ser-795, cyclin E and increased amounts of the cell
      cycle inhibitors p27(Kip1) and p21(Cip1). Finally, STAT1 deficient cells not only
      proliferate at a greater rate, but have enhanced phosphorylated pRb-(S795),
      cyclin E and reduced p27(Kip1) and p21(Cip1). Our results suggest that there is a
      time-dependent hierarchy of events following IFN-gamma-STAT1 which begins with
      the rapid reduction of cyclin D1 levels that is dependent on STAT1 directly
      interacting with the cyclin D1/Cdk4 complex. This is then followed by a later
      sustained up-regulation of p27(Kip1) and p21(Cip1) that may be dependent on STAT1
      transcriptional activity. Thus, these results highlight a dual role of STAT1 that
      may require both its non-transcriptional as well as it known transcriptional
      function.

PMID- 21084837
TI  - Prion protein in Caenorhabditis elegans: Distinct models of anti-BAX and
      neuropathology.
AB  - The infectious agent of prion diseases is believed to be nucleic acid-free
      particles composed of misfolded conformational isomers of a host protein known as
      prion protein (PrP). Although this "protein-only" concept is generally accepted,
      decades of extensive research have not been able to elucidate the mechanisms by
      which PrP misfolding leads to neurodegeneration and infectivity. The challenges
      in studying prion diseases relate in part to the limitations of mammalian prion
      models, which include the long incubation period post-infection until symptoms
      develop, the high expense of maintaining mammals for extended periods, as well as
      safety issues. In order to develop prion models incorporating a genetically
      tractable simple system with a well-defined neuronal system, we generated
      transgenic C. elegans expressing the mouse PrP behind the pan-neuronal ric-19
      promoter (Pric-19). We show here that high expression of Pric-19::PrP in C.
      elegans can result in altered morphology, defective mobility, and shortened
      lifespan. Low expression of Pric-19::PrP, however, does not cause any detectable
      harm. Using the dopamine neuron specific promoter Pdat-1, we also show that
      expression of the murine BAX, a pro-apoptotic member of the Bcl-2 family, causes
      dopamine neuron destruction in the nematode. However, co-expression of PrP
      inhibits BAX-mediated dopamine neuron degeneration, demonstrating for the first
      time that PrP has anti-BAX activity in living animals. Thus, these distinct PrP
      transgenic C. elegans lines recapitulate a number of functional and
      neuropathological features of mammalian prion models, and provide an opportunity
      for facile identification of genetic and environmental contributors to prion
      associated pathology.

PMID- 21084838
TI  - Combination of the somatic cell nuclear transfer method and RNAi technology for
      the production of a prion gene-knockdown calf using plasmid vectors harboring the
      U6 or tRNA promoter.
AB  - By combining RNAi technology with SCNT method, we attempted to produce transgenic
      calves with knocked down bPRNP for technological assessments. The respective
      utilities of type II (tRNA) and type III (hU6) Pol III promoters in mediating
      plasmid vector-based RNAi for the production of a bPRNP-knockdown calf were
      compared. Plasmid harboring DNA for siRNA expression was introduced stably into
      the genome of primary cultured bovine cells. By inserting the transgenic cell
      into an enucleated bovine egg, SCNT embryos were produced. The ability for SCNT
      embryos to develop to blastocysts was higher in hU6 based vector groups (44-53%)
      than in a tRNA group (32%). In all, 30 hU6-embryos and 12 tRNA-embryos were
      transferred to 11 recipients. Only tRNA-embryos were able to impregnate
      recipients (6 out of 11 transfers), resulting in four aborted fetuses, one
      stillbirth, and one live-born calf. The expression of EGFP, a marker, was
      detected in all six. The bPRNP transcript levels in the nervous tissues (brain,
      cerebellum, spinal bulb, and spinal cord) from the calf, which was killed 20 days
      after birth, were reduced to 35% of those of the control calf on average, as
      determined by qRT-PCR. The PrPC levels, as estimated by western blot were reduced
      to 86% on average in the nervous tissues. These findings suggest that SCNT
      technology remains immature, that the tRNA promoter is useful, and that RNAi can
      significantly reduce PRNP mRNA levels, but insufficient reduction of PrPC levels
      exists in cattle under these conditions.

PMID- 21084839
TI  - Bacterial vaccine discovery: from "brute force" to high selectivity.

PMID- 21084841
TI  - Post-translational regulation of mitogen-activated protein kinase phosphatase-2
      (MKP-2) by ERK.
AB  - MKP-2 is a member of the dual-specificity phosphatase family that can
      dephosphorylate and inactivate mitogen-activated protein kinases (MAPKs).
      Although MKP-2 can be induced by ERK signaling, little is known about the
      regulation of MKP-2 at the post-translational level. Here we show that MKP-2 is
      phosphorylated by ERK and that such phosphorylation leads to stabilization of MKP
      2 protein. Importantly, we find that MKP-2 can be phosphorylated on Ser386 and
      Ser391 at its C-terminus. Blockage of ERK activation results in enhanced
      proteasomal degradation of MKP-2 protein. Moreover, we find that phosphorylation
      has no effect on MKP-2 phosphatase activity. Taken together, these results
      illustrate an important post-translational regulation of MKP-2 protein as a
      feedback mechanism to control ERK activity.

PMID- 21084840
TI  - The Mek1 phosphorylation cascade plays a role in meiotic recombination of
      Schizosaccharomyces pombe.
AB  - Mek1 is a Chk2/Rad53/Cds1-related protein kinase that is required for proper
      meiotic progression of Schizosaccharomyces pombe. However, the molecular
      mechanisms of Mek1 regulation and Mek1 phosphorylation targets are unclear. Here,
      we report that Mek1 is phosphorylated at serine-12 (S12), S14 and threonine-15
      (T15) by Rad3 (ATR) and/or Tel1 (ATM) kinases that are activated by meiotic
      programmed double-strand breaks (DSBs). Mutations of these sites by alanine
      replacement caused abnormal meiotic progression and recombination rates.
      Phosphorylation of these sites triggers autophosphorylation of Mek1; indeed,
      alanine replacement mutations of Mek1-T318 and -T322 residues in the activation
      loop of Mek1 reduced Mek1 kinase activity and meiotic recombination rates.
      Substrates of Mek1 include Mus81-T275, Rdh54-T6 and Rdh54-T673. Mus81-T275 is
      known to regulate the Mus81 function in DNA cleavage, whereas Rdh54-T6A/T673A
      mutant cells showed abnormal meiotic recombination. Taken together, we conclude
      that the phosphorylation of Mek1 by Rad3 or Tel1, Mek1 autophosphorylation and
      Mus81 or Rdh54 phosphorylation by Mek1 regulate meiotic progression in S. pombe.

PMID- 21084843
TI  - Endothelial cells in pancreatic islet development and function.
AB  - Endothelial cells represent one of the most abundant and widely found cell types
      in the mammalian embryo. These cells arise in close proximity with and often as
      an integral part of several organs such as the kidneys, lungs, liver and
      pancreas. In most of these organs, they play an instructive role to determine the
      fate of progenitor cells in the developing embryo. Studies carried out until now
      by Eckhard Lammert, Douglas Melton, Ken Zaret and colleagues have convincingly
      demonstrated the importance of endothelial cells in normal development of the
      pancreas. This article reviews the literature in development of endothelial and
      endodermal cells. Understanding these endothelium-derived signaling mechanisms
      that allow differentiation of endodermal cells to endocrine pancreatic lineage
      will help us develop strategies for making insulin-producing cells in vitro.

PMID- 21084844
TI  - Bone marrow transplantation stimulates pancreatic beta-cell replication after
      tissue damage.
AB  - Bone marrow transplantation has been shown to normalize hyperglycemia but the
      mechanisms underlying pancreatic beta-cell regeneration remain elusive. Here, we
      investigate the capacity of transplanted bone marrow cells to engraft into the
      pancreas, to adopt an endothelial cell phenotype and to stimulate beta-cell
      regeneration after islet damage. Genetically marked whole bone marrow from Tie2
      Cre/ZEG mice was transplanted into lethally irradiated wild-type mice. The fate
      of the transplanted cells, as well as blood glucose levels and beta-cell mass
      dynamics, was investigated in normal and hyperglycemic recipient mice. Bone
      marrow transplantation significantly increased beta-cell mass and reduced the
      hyperglycemia of mice subjected to beta-cell damage by streptozotocin (STZ). This
      was associated with enhanced replication of pre-existing beta-cells, proportional
      to the degree of beta-cell damage, whereas no evidence was obtained for islet
      neogenesis. The engrafted bone marrow-derived cells in the pancreas showed little
      capacity to differentiate into blood vessel endothelium but retained a myeloid
      cell fate. By contrast, the transplantation evoked pronounced proliferation of
      recipient endothelial cells. These findings illuminate an important adjuvant
      function of transplanted bone marrow cells in both angiogenesis and beta-cell
      regeneration. This may have interesting clinical implications, not least for
      human islet transplantation endeavours, where co-transplantation of islets with
      bone marrow cells might represent a simple means to improve islet survival and
      function.

PMID- 21084845
TI  - Activation of NFkappaB dependent apoptotic pathway in pancreatic islet cells by
      hypoxia.
AB  - Insulin producing beta-cells are exposed to hypoxic stress in the early period
      after islet transplantation. Although it has been suggested that hypoxia leads to
      islet loss, the underlying mechanisms are unclear. In this study, the early
      transcriptional profiles of b cell response to hypoxia were determined by using
      the Affymetrix Murine Genome Array U74Av2 GeneChip (about 12,422 genes). In
      addition to the upregulation of genes associated with glycolysis, genes related
      to apoptosis and stress response were also upregulated. The downregulated genes
      on hypoxia are classified as transcription and inflammatory response. These
      findings were confirmed by TUNEL assay and real-time reverse transcription-PCR
      for mRNA of genes related to apoptosis. On the other hand, we have found that the
      transcription factor NFkappaB was activated by hypoxia in islet cells. The
      affected genes involved in the activated NFkappaB pathway were mainly categorized
      as apoptosis-related genes by quantitative real-time PCR array (84 genes). Our
      comprehensive analysis of transcriptional changes of islets by hypoxia may assist
      the development of strategies that protect islet grafts from early loss.

PMID- 21084846
TI  - Factors affecting islet graft embolization in the liver of diabetic mice.
AB  - BACKGROUND: Embolic occlusion of the portal vein due to islet transplantation is
      one of the major reasons for reduced survival of transplanted islets. In this
      study, we examined the location of islets as well as the correlation between
      islet and portal vein size after intraportal islet transplantation, and evaluated
      liver and islet pathology. METHODS: BALB/c mice were intraportally transplanted
      with 800 islets and the liver was examined at postoperative day (POD) 0 (n=7),
      POD 2 (n=4) and POD 28 (n=3). Liver specimens were stained for hematoxylin and
      eosin (necrosis), insulin, and TUNEL (apoptosis). We evaluated distance from
      liver surface to islets, islet and portal vein diameter, embolic ratio (islet
      diameter/portal vein diameter), apoptosis/necrosis of islets and
      apoptosis/necrosis of the liver tissue surrounding the islet. RESULTS: The liver
      was divided into peripheral and central sites. Islet and liver apoptosis/necrosis
      were significantly higher at peripheral sites. In regions without liver apoptosis
      or necrosis, portal vein diameter was significantly larger and embolic ratios
      were significantly lower. CONCLUSION: Transplanted islets and liver tissue
      exhibited more injury at peripheral sites, in part, due to smaller diameters of
      portal venules that result in more frequent emboli following islet
      transplantation.

PMID- 21084847
TI  - Expression and regulation of osteopontin in type 1 diabetes.
AB  - Osteopontin (OPN) is a secreted acidic phosphoprotein that is involved in many
      inflammatory and immune-modulating disorders. We previously demonstrated that OPN
      is a novel islet protein and a pro survival factor that may serve as an intrinsic
      feedback regulator of nitric oxide signaling in beta-cells. Here, we investigated
      the endogenous expression of pancreatic OPN in non obese diabetic (NOD) mice and
      explored its regulation in the islets and b-cells. High levels of pancreatic OPN
      mRNA and protein were seen in the prediabetic NOD mice pancreata. The temporal
      pattern of OPN expression inversely correlated with progression of insulitis and
      beta-cell destruction. Immunostaining of pancreatic serial sections showed co
      localization of OPN with most of the islet hormones. Next we investigated the
      regulation of OPN in the islets and beta-cells. Naturally occurring early
      upregulation of OPN transcription was seen after exposure of native normoglycemic
      NOD islets and beta-cells to a high-dose combination of IL-1beta, TNF-alpha and
      IFN-gamma. To distinguish between the effect of cytokines and high glucose on OPN
      transcription, RINm5F cells were transfected with luciferase-labeled rat OPN
      promoter and treated with cytokines or glucose. Cytokines induced upregulation of
      OPN promoter activity within one hour, while glucose induced a dose-dependent
      upregulation of OPN promoter activity after 24 hrs. Long-term exposures to
      cytokines or glucose reduced OPN expression and promoter activity. Our data
      provide the first observations into the presence of a positive intrinsic
      mechanism that regulates pancreatic OPN expression. Based upon previous studies
      that support a protective role of OPN in the islets, our data suggest that
      exhaustion of this local OPN system is implicated in the associated loss of
      endogenous islet protection and progression of the destructive insulitis and
      diabetes severity in the NOD mouse model.

PMID- 21084848
TI  - Rapamycin does not adversely affect intrahepatic islet engraftment in mice and
      improves early islet engraftment in humans.
AB  - OBJECTIVE: In this study we examined the effect of rapamycin (RAPA), a key
      component of the immunosuppressive regimen in clinical islet transplantation, on
      islet engraftment and function in vivo. METHODS AND RESULTS: Diabetic C57BL/6 or
      BALB/C recipient mice were transplanted with 350 syngeneic islets through the
      portal vein (PV-Tx; C57BL/6 n = 60; BALB/C n = 22) and treated with once-daily
      oral RAPA (1 mg/kg) or vehicle. No differences in post-transplant blood glucose
      concentrations and glucose tolerance were observed between RAPA- and vehicle
      treated mice. The impact of RAPA on human islet engraftment was assessed in 10
      patients with type 1 diabetes treated with : 0.1 mg/kg/day rapamycin before islet
      transplantation. Compared to non pre-treated islet transplant recipients (n =
      12), RAPA pre-treated patients had increased blood RAPA concentrations (p =
      0.006) and fasting C-peptide concentrations (p = 0.005) in the two weeks post
      transplant. RAPA pre-treatment was associated with a reduction in chemokines CCL2
      and CCL3 concentrations pre-transplant (p < 0.01), and a dampened chemokine
      response (p = 0.005) post-transplant. Concordantly, in vitro RAPA inhibited the
      secretion of CCL2 and CCL3 by monocytes. CONCLUSION: Rapamycin does not adversely
      affect intrahepatic islet engraftment in the mouse, and potentially improves
      islet engraftment in humans by an anti-inflammatory mechanism.

PMID- 21084850
TI  - Effect of upregulation of NeuroD in insulin-producing liver cells.
AB  - NeuroD (BETA2), a bHLH transcription factor is known to be involved in early
      pancreatic endocrine as well as neuronal differentiation. NeuroD is known to
      regulate distinct sets of molecules that are important for survival and
      differentiation of pancreatic cells. We assessed whether forced expression of
      NeuroD, can induce maturation of FAO-ins liver cells to beta-like cells. To test
      this we stably transfected NeuroD into these cells that constitutively secrete
      insulin. Transfected cells showed enhanced expression of preproinsulin mRNA,
      elevated insulin content and cumulative insulin secretion. There was an up
      regulation of expression of the genes for the transcription factor Foxa2, L-type
      Ca2+ channels subunit alpha 1C and alpha 1D and secretory granular protein
      chromogranin A. These FAO-ins-hNd cells show increased insulin secretion in
      response to calcium and theophylline, but not glucose. However, secretion of
      insulin remained constitutive rather than regulated. These studies demonstrate
      that NeuroD alone may not be sufficient to induce regulated insulin release in
      insulin-producing liver cells.

PMID- 21084849
TI  - Reduction of ischemic cell death in cultured Islets of Langerhans by the
      induction of cytoglobin.
AB  - Despite the source or mechanism of origin of islets of Langerhans or islet beta
      cells, all suffer significant cell loss from ischemia after isolation, thereby
      reducing the surviving islet mass available for study or transplantation. Methods
      to reduce beta cell death after islet isolation and transplantation must be
      developed if islet transplantation is to become an accepted treatment for
      diabetes. In order to enhance intracellular oxygen delivery and utilization,
      islets were transfected with a plasmid encoding cytoglobin, an intracellular
      oxygen binding protein. Oxygen consumption, insulin secretion, and the degree of
      central islet necrosis were measured in untreated and transfected islets to test
      the effects of cytoglobin on islet survival and function in vitro. The presence
      of cytoglobin reduced islet cell loss by reducing hypoxia related central islet
      necrosis and increased insulin secretion as compared with untreated islets.
      Cytoglobin treated islets maintained a normal rate of oxygen consumption, while
      untreated islets increased the rate of oxygen consumption caused by a shift to
      anaerobic metabolism and increased reactive oxygen specie synthesis. The
      induction of cytoglobin in islets may reduce cell loss from chronic hypoxia and
      may be a useful adjunct to islet transplantation.

PMID- 21084851
TI  - Gene expression profiling of HUH7-ins: lack of a granulogenic function for
      chromogranin A.
AB  - Previously, the insulin producing liver cell line HUH7-ins has been shown to
      synthesize, store and secrete insulin in response to glucose via secretory
      granules. The current study characterized the gene expression profile of HUH7-ins
      with the aim to identify changes possibly involved in the formation of granules.
      Additionally, experiments were conducted to determine the influence of
      chromogranin A (CgA) on secretory granule biogenesis (SGB) in HUH7-ins.
      Expression of 165 genes were significantly changed in HUH7-ins,though
      interestingly the majority of secretory granule associated genes, such as the
      chromogranins were unchanged. CgA was over-expressed in glucose unresponsive HUH7
      ins cells to test whether CgA played a role in SGB and would restore the
      regulated secretory phenotype. Over-expression affected neither the storage nor
      regulated secretion of insulin. These data suggest that SGB may by regulated at a
      post-transcriptional level with no evidence to indicate that CgA regulates SGB in
      the cell line HUH7-ins.

PMID- 21084852
TI  - Identification of a novel mechanism regulating beta-cell mass: neuronal relay
      from the liver to pancreatic beta-cells.
AB  - Recent studies have demonstrated that beta-cell replication plays a central role
      in maintaining adult beta-cell mass. beta-cell proliferative activity changes
      dynamically to meet systemic needs throughout life. One condition in which beta
      cell proliferation is enhanced is obesity-related insulin resistance. However,
      the mechanism underlying this compensatory beta-cell response is not well
      understood. We have identified a neuronal relay, originating in the liver, which
      enhances both insulin secretion and pancreatic beta-cell proliferation. Blockade
      of this neural relay in murine obesity models inhibited pancreatic islet
      expansion during obesity development, showing this inter-organ communication
      system to be physiologically involved in compensatory beta-cell proliferation.
      While there is controversy about which mechanism, proliferation of pre-existing
      beta-cells or production of new beta cells from progenitor cells, plays the
      dominant role in maintaining or regulating beta-cell mass, we herein provide an
      example that proliferation of pre-existing beta-cells contributes to a beta-cell
      increment in obesity-related insulin resistance. Furthermore, we have shown the
      potential for clinical application of this inter-organ system as a therapeutic
      target for insulin-deficient diabetes.

PMID- 21084853
TI  - All together now: exocytose or fail.
AB  - Compact and complex syncytium is a normal cellulo-social context for beta-cells
      within the healthy pancreatic islet. Optimal cell-to-cell electrical coupling
      through Connexin36 (Cx36) seems to ensure coordinated plasma membrane
      depolarization pattern and insulin exocytosis. Both phenomena can be further
      modulated by rich pancreas innervation. The complex structure and coordinated
      action develop after birth during fast hypertrophy and hyperplasia of the
      endocrine tissue and are maintained throughout adult life. The properties that
      emerge from the structure and coordination can disappear due to various reasons
      later in life and can lead to glucose intolerance and diabetes mellitus. In
      majority of cases the islet structure is lost after extensive beta-cell death in
      long-term hyperglycemia.

PMID- 21084854
TI  - Autologous hematopoietic stem cell transplantation in type 1-diabetes.
AB  - A type 1-diabetes results from autoimmune destruction of the insulin producing
      beta-cells in the pancreas. Today there is no cure to the disorder, and the
      patients require life-long insulin medication to survive. Treatment with
      exogenous insulin cannot mimic the second-by second regulation of blood glucose
      levels achieved by the beta-cells, and the current regimen presents a difficult
      navigation between the Scylla of life-threatening hypoglycemia and the Charybdis
      of hyperglycemic tissue glycosylation and late-complications.

PMID- 21084855
TI  - In pursuit of ryanodine receptors gating in the plasma membrane of RINm5F
      pancreatic beta-cells.

PMID- 21084856
TI  - Expression of the new CXCL12 receptor, CXCR7, in gliomas.
AB  - Gliomas are very invasive brain tumors with poor prognosis and therefore any
      attempt to limit tumor cell dissemination in the brain is expected to improve
      glioma treatment. The recent deorphanization of CXCR7 as additional receptor for
      CXCL12 and CXCL11 has raised key issues on its interaction with the CXCL12/CXCR4
      axis as a mechanism to modulate glioma cell migration. In this work we
      investigated protein and mRNA expression of the two chemokines CXCL12 and CXCL11,
      together with their receptors CXCR4 and CXCR7 in human glioma specimens and cell
      lines by immunohistochemistry, flow cytometry and quantitative real-time PCR. The
      main purpose of this study was to find out whether and at what extent CXCR4 and
      CXCR7 are differentially expressed in glioma cells. In human glioma specimens the
      levels of CXCL11 and CXCR4 mRNA were significantly higher in glioblastomas
      compared to non-tumor controls or low grade gliomas, whilst no difference was
      found for CXCL12 and CXCR7 mRNA expression. In cell lines, flow cytometry and
      immunocytochemical experiments showed CXCR4 was mainly expressed irrespective of
      its membrane or intracellular localization. In contrast, a predominant
      intracellular localization together with a negligible membrane expression of
      CXCR7 was found in all cells examined. In in vitro experiments CXCR4 and CXCR7
      antagonists and the silencing of CXCR4 showed complete inhibition of glioma
      proliferation. Our findings, in agreement with previous data, suggest that in
      human glioma cells the prevalent intracellular localization of CXCR7 might
      modulate the functionality of CXCL11/12 either acting as a scavenger for these
      chemokines or interfering with the signaling pathways activated by the
      stimulation of CXCR4.

PMID- 21084857
TI  - Cytoplasmic compartmentalization of SOX9 abrogates the growth arrest response of
      breast cancer cells that can be rescued by trichostatin A treatment.
AB  - We have previously reported that although SOX9 is a transcription factor, it is
      often localized in the cytoplasm of some invasive and metastatic breast
      carcinomas. To determine whether cytoplasmic compartmentalization is a common
      mechanism utilized by cancer cells to proliferate indefinitely, SOX9 localization
      was examined at different stages of development in normal mouse mammary glands
      and in cancer cells. We show here that SOX9 expression is nuclear in ductal
      epithelial cells throughout mammary gland development and differentiation but is
      localized in the cytoplasm of some breast cancer cell lines (BCCLs). Furthermore,
      cytoplasmic localization of SOX9 is associated with abrogation of the growth
      arrest response of breast cancer cells and results from dysregulated HDAC
      activity rather than defects in its nuclear export. Immuno-precipitation and
      immunoblot studies revealed that inhibiting HDAC activity with Trichostatin A can
      rescue this defect by up-regulating acetylated SOX9 and p21 expression that
      results in increased cell death. Our data suggests nuclear SOX9 expression
      parallels development and differentiation but cytoplasmic SOX9 expression is
      associated with abrogation of growth arrest response of breast cancer cells. Such
      expressions may be a common mechanism utilized by some transformed breast cancer
      cells to proliferate indefinitely.

PMID- 21084858
TI  - Inhibition of tumor growth and vasculogenic mimicry by curcumin through down
      regulation of the EphA2/PI3K/MMP pathway in a murine choroidal melanoma model.
AB  - This study aims to investigate the underlying mechanism by which curcumin
      inhibits tumor growth and reduces vasculogenic mimicry (VM) in a murine choroidal
      melanoma model. Sixty mice were given subretinal injection with B16F10 cells and
      divided into a treatment and a control group. Curcumin was administered to the
      treatment group once a day at a dose of 100 mg/kg for 18 days starting at d3 (the
      day of inoculation is designated as d0); an equivalent volume of poloxamer-F68
      was administered to the control group. Immunohistochemical and histochemical
      double staining were ued to detect the different blood supply patterns. The
      amounts of epithelial cell kinase (EphA2), phosphatidylinositol-3-kinase (PI3K),
      and matrixmetalloproteinase-2 and -9 (MMP-2, MMP-9) proteins expressed in the
      tumor tissue were analyzed using immunohistochemical staining; mRNA levels were
      measured using real-time PCR analysis. Results indicate that the tumor volume is
      reduced (P=0.000) and that the numbers of VM (P=0.000), mosaic vessels (P=0.031),
      and endothelium-dependent vessels (P=0.000) are significantly decreased by
      curcumin (P=0.001). The expression levels of EphA2, PI3K, MMP-2, and -9 are also
      lower in the treatment group than in the control group (P=0.001); similarly, mRNA
      levels in the treatment group are lower than those in the control group
      (P=0.000). In conclusion, curcumin has the ability to inhibit the growth of
      engrafted melanoma VM channels through the regulation of vasculogenic factors
      that could be related to the down-regulation of the EphA2/PI3K/MMPs signaling
      pathway. Thus, curcumin has the potential of being a clinical inhibitor of VM of
      choroidal melanoma.

PMID- 21084859
TI  - CaV1.3 as pacemaker channels in adrenal chromaffin cells: specific role on exo-
      and endocytosis?
AB  - Voltage-gated L-type calcium channels (LTCCs) are expressed in adrenal chromaffin
      cells. Besides shaping the action potential (AP), LTCCs are involved in the
      excitation-secretion coupling controlling catecholamine release and in Ca (2+) 
      dependent vesicle retrieval. Of the two LTCCs expressed in chromaffin cells
      (CaV1.2 and CaV1.3), CaV1.3 possesses the prerequisites for pacemaking
      spontaneously firing cells: low-threshold, steep voltage-dependence of activation
      and slow inactivation. By using CaV1 .3 (-/-) KO mice and the AP-clamp it has
      been possible to resolve the time course of CaV1.3 pacemaker currents, which is
      similar to that regulating substantia nigra dopaminergic neurons. In mouse
      chromaffin cells CaV1.3 is coupled to fast-inactivating BK channels within
      membrane nanodomains and controls AP repolarization. The ability to carry
      subthreshold Ca (2+) currents and activate BK channels confers to CaV1.3 the
      unique feature of driving Ca (2+) loading during long interspike intervals and,
      possibly, to control the Ca (2+) -dependent exocytosis and endocytosis processes
      that regulate catecholamine secretion and vesicle recycling.

PMID- 21084860
TI  - Aggressive myeloid leukemia formation is directed by the Musashi 2/Numb pathway.
AB  - Chronic myeloid leukemia (CML) progresses from a chronic phase to a deadly blast
      crisis phase. While it is known that BCR-ABL initiates the disease and that
      secondary molecular and genetic abnormalities likely contribute to progression of
      the disease to blast crisis, details regarding the mechanism(s) of blast phase
      progression are lacking. Two recent reports identify Musashi 2 (Msi2) as a key
      regulator in the progression of CML from the chronic phase to blast crisis. These
      reports demonstrated that the cell fate determination protein, Numb, was
      downregulated in blast crisis CML and that exogenous expression of Numb inhibited
      leukemogenesis. Correspondingly, Msi2 was shown to be upregulated in blast crisis
      CML and to negatively regulate expression of Numb. Exogenous expression of Msi2
      enhanced the formation of an aggressive immature leukemia induced by BCR-ABL.
      High expression of Msi2 was also found in leukemic cells of AML patients and
      elevated Msi2 expression was shown to associate with poor prognosis in both AML
      and CML. These reports together highlight the apparent role of the Musashi-Numb
      pathway in regulating the formation of aggressive myeloid leukemia, and thus
      provide a potential molecular mechanism for the transition of chronic phase CML
      to the deadly blast crisis. Importantly, this work suggests this pathway may
      provide targets for future therapies that are desperately needed for aggressive
      forms of myeloid leukemia.

PMID- 21084861
TI  - Sir2-dependent daughter-to-mother transport of the damaged proteins in yeast is
      required to prevent high stress sensitivity of the daughters.
AB  - The budding yeast Saccharomyces cerevisiae actively transports adverse factors
      (e.g. oxidized proteins) from the daughter to mother cells. The transport is
      believed to ensure that the daughters are born "young", thus preventing clonal
      senescence. Is this the only reason for the existence of such transport? We
      subjected yeast cells to various stress conditions and compared survival of
      mother and daughter cells. It was found that replicative age-dependent mortality
      under our experimental stress conditions was U-shaped: the resistance of both
      virgin daughters and old mother cells (more than three bud scars) was lower
      compared to the young mothers. SIR2 mutants were shown to fail to maintain the
      mother-daughter asymmetry. We showed that sir2 knockout affects the relative
      stress resistance in favor of the mothers. Thus, daughter cells are more
      vulnerable to a variety of stresses than the young mothers, and Sir2-dependent
      transport of the adverse factors acts to equalize the resistance.

PMID- 21084862
TI  - Merlin's tumor suppression linked to inhibition of the E3 ubiquitin ligase CRL4
      (DCAF1).
AB  - The mechanism by which the FERM domain protein Merlin, encoded by the tumor
      suppressor NF2, restrains cell proliferation is poorly understood. Prior studies
      have suggested that Merlin exerts its antimitogenic effect by interacting with
      multiple signaling proteins located at or close to the plasma membrane. We have
      recently observed that Merlin translocates into the nucleus and binds to and
      inhibits the E3 ubiquitin ligase CRL4 (DCAF1) . Genetic evidence indicates that
      inactivation of Merlin induces oncogenic gene expression, hyperproliferation, and
      tumorigenicity by unleashing the activity of CRL4 (DCAF1) . In addition to
      providing a potential explanation for the diverse effects that loss of Merlin
      exerts in multiple cell types, these findings suggest that compounds inhibiting
      CRL4 (DCAF1) may display therapeutic efficacy in Neurofibromatosis type 2 and
      other cancers driven by Merlin inactivation.

PMID- 21084864
TI  - Astrocyte-elevated gene-1 (AEG-1) induction by hypoxia and glucose deprivation in
      glioblastoma.
AB  - Glioblastomas continue to carry poor prognoses for patients despite advances in
      surgical, chemotherapeutic, and radiation regimens. One feature of glioblastoma
      associated with poor prognosis is the degree of hypoxia and expression levels of
      hypoxia-inducible factor-1 alpha (HIF-1alpha). HIF-1alpha expression allows
      metabolic adaptation to low oxygen availability, partly through upregulation of
      VEGF and increased tumor angiogenesis. Here, we demonstrate an induced level of
      astrocyte-elevated gene-1 (AEG-1) by hypoxia in glioblastoma cells. AEG-1 has the
      capacity to promote anchorage-independent growth and cooperates with Ha-ras in
      malignant transformation. In addition, AEG-1 was recently demonstrated to serve
      as an oncogene and can induce angiogenesis in glioblastoma. Results from in vitro
      studies show that hypoxic induction of AEG-1 is dependent on HIF-1alpha
      stabilization during hypoxia and that PI3K inhibition abrogates AEG-1 induction
      during hypoxia through loss of HIF-1alpha stability. Furthermore, we show that
      AEG-1 is induced by glucose deprivation and that prevention of intracellular
      reactive oxygen species (ROS) production prevents this induction. Additionally,
      AEG-1 knockdown results in increased ROS production and increased glucose
      deprivation-induced cytotoxicity. On the other hand, AEG-1 overexpression
      prevents ROS production and decreases glucose deprivation-induced cytotoxicity,
      indicating that AEG-1 induction is necessary for cells to survive this type of
      cell stress. These observations link AEG-1 overexpression in glioblastoma with
      hypoxia and glucose deprivation, and targeting these physiological pathways may
      lead to therapeutic advances in the treatment of glioblastoma in the future.

PMID- 21084865
TI  - Induction of a fast inactivation gating on delayed rectifier Shab K(+) channels
      by the anti-inflammatory drug celecoxib.
AB  - Celecoxib is a drug designed to selectively inhibit COX-2, an inflammation
      inducible cyclooxygenase isoform, over the constitutively expressed COX-1
      isoform. In addition to this selective inhibition it is now known that celecoxib
      exerts a variety of effects on several types of ion channels, thus producing
      secondary physiological effects. In this work we demonstrate that at
      therapeutically relevant concentrations celecoxib interacts with Shab K(+)
      channels specifically promoting a fast inactivation gating (without blocking the
      pore or significantly affecting other gating processes). At least two celecoxib
      molecules bind to each channel promoting a fast inactivation that develops from
      both open and closed states. Channel inactivation in turn causes a reduction of
      the size of I(K). Taken together, our observations show that in addition to its
      intended therapeutic target celecoxib is a useful tool to further study the
      mechanism of Shab channel inactivation.

PMID- 21084863
TI  - Structural models of TREK channels and their gating mechanism.
AB  - Mechanosensitive TREK channels belong to the family of K2P channels, a family of
      widely distributed, well modulated channels that uniquely have two similar or
      identical subunits, each with two TM1-P-TM2 motifs. Our goal is to build viable
      structural models of TREK channels, as representatives of K2P channels family.
      The structures available to be used as templates belong to the 2TM channels
      superfamily. These have low sequence similarity and different structural
      features: four symmetrically arranged subunits, each having one TM1-P-TM2 motif.
      Our model building strategy used two subunits of the template (KcsA) to build one
      subunit of the target (TREK-1). Our models of the Closed channel were adjusted to
      differ substantially from those of the template, e.g., TM2 of the 2nd repeat is
      near the axis of the pore whereas TM2 of the 1st repeat is far from the axis.
      Segments linking the two repeats and immediately following the last TM segment
      were modeled ab initio as alpha-helices based on helical periodicities of
      hydrophobic and hydrophilic residues, highly conserved and poorly conserved
      residues, and statistically related positions from multiple sequence alignments.
      The models were further refined by two-fold symmetry-constrained MD simulations
      using a protocol we developed previously. We also built models of the Open state
      and suggest a possible tension-activated gating mechanism characterized by
      helical motion with two-fold symmetry. Our models are consistent with
      deletion/truncation mutagenesis and thermodynamic analysis of gating described in
      the accompanying paper.

PMID- 21084866
TI  - Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN
      anti-invasion pathway.
AB  - We have recently identified mutually antagonizing signaling pathways that
      regulate podosome formation and invasive phenotypes in Src-transformed vascular
      smooth muscle cells and fibroblasts. Cross-talks between the anti-invasion p53
      PTEN, and the pro-invasion Src-Stat3 and Src-PI3K-Akt pathways serve as a check
      and balance that dictates the outcome of either an invasive or non-invasive
      phenotype. Using a retrovirus vector encoding PTEN phosphatase mutants that
      retain either protein- or lipid-phosphatase activity on a Src(Y527F)background,
      we report here that both lipid- and protein-phosphatase activities of PTEN
      contribute to the suppression of Src-induced podosome formation and associated
      invasive phenotypes in rat aortic smooth muscle cells. This data suggests that
      p53 up-regulation of PTEN inhibits cell invasion via a two-prong mechanism:
      inactivating podosome agonists by its protein-phosphatase activity on the one
      hand, and antagonising the PI3K-Akt pathway by its lipid-phosphatase activity on
      the other.

PMID- 21084868
TI  - Perturbation of Spc25 expression affects meiotic spindle organization, chromosome
      alignment and spindle assembly checkpoint in mouse oocytes.
AB  - Spc25 is a component of the Ndc80 complex which consists of Ndc80, Nuf2, Spc24,
      and Spc25. Previous work has shown that Spc25 is involved in regulation of
      kinetochore microtubule attachment and the spindle assembly checkpoint in
      mitosis. The roles of Spc25 in meiosis remain unknown. Here, we report its
      expression, localization and functions in mouse oocyte meiosis. The Spc25 mRNA
      level gradually increased from the GV to MI stage, but decreased by MII during
      mouse oocyte meiotic maturation. Immunofluorescent staining showed that Spc25 was
      restricted to the germinal vesicle, and associated with chromosomes during all
      stages after GVBD. Overexpression of Spc25 by mRNA injection resulted in oocyte
      meiotic arrest, chromosome misalignment and spindle disruption. Conversely, Spc25
      RNAi by siRNA injection resulted in precocious polar body extrusion and caused
      severe chromosome misalignment and aberrant spindle formation. Our data suggest
      that Spc25 is required for chromosome alignment, spindle formation, and proper
      spindle checkpoint signaling during meiosis.

PMID- 21084867
TI  - Tumor viruses and cancer biology: Modulating signaling pathways for therapeutic
      intervention.
AB  - Tumor viruses have provided relatively simple genetic systems, which can be
      manipulated for understanding the molecular mechanisms of the cellular
      transformation process. A growing body of information in the tumor virology field
      provides several prospects for rationally targeted therapies. However, further
      research is needed to better understand the multiple mechanisms utilized by these
      viruses in cancer progression in order to develop therapeutic strategies.
      Initially viruses were believed to be associated with cancers as causative agents
      only in animals. It was almost half a century before the first human tumor virus,
      Epstein-Barr virus (EBV), was identified in 1964. Subsequently, several human
      tumor viruses have been identified including Kaposi sarcoma associated
      herpesvirus (KSHV), human Papillomaviruses (HPV), Hepatitis B virus (HBV),
      Hepatitis C virus (HCV), Human T lymphotropic virus (HTLV-1) and recently
      identified Merkel cell Polyomavirus (MCPyV). Tumor viruses are sub-categorized as
      either DNA viruses, which include EBV, KSHV, HPV, HBV, and MCPyV, or RNA viruses
      such as HCV and HTLV-1. Tumor-viruses induce oncogenesis through manipulating an
      array of different cellular pathways. These viruses initiate a series of cellular
      events, which lead to immortalization and proliferation of the infected cells by
      disrupting the mitotic checkpoint upon infection of the host cell. This is often
      accomplished by functional inhibition or proteasomal degradation of many tumor
      suppressor proteins by virally encoded gene products. The virally infected cells
      can either be eliminated via cell-mediated apoptosis or persist in a state of
      chronic infection. Importantly, the chronic persistence of infection by tumor
      viruses can lead to oncogenesis. This review discusses the major human tumor
      associated viruses and their ability to modulate numerous cell signaling
      pathways, which can be targeted for potential therapeutic approaches.

PMID- 21084870
TI  - Evidence-based medicine: inherent limitations.

PMID- 21084871
TI  - Using consensus to build wound care evidence: the story of SCALE.

PMID- 21084875
TI  - The 2011 OIG Work Plan has been released: clinicians must remember to read it!

PMID- 21084869
TI  - To polyadenylate or to deadenylate: that is the question.
AB  - mRNA polyadenylation and deadenylation are important processes that allow rapid
      regulation of gene expression in response to different cellular conditions.
      Almost all eukaryotic mRNA precursors undergo a co-transcriptional cleavage
      followed by polyadenylation at the 3' end. After the signals are selected,
      polyadenylation occurs to full extent, suggesting that this first round of
      polyadenylation is a default modification for most mRNAs. However, the length of
      these poly(A) tails changes by the activation of deadenylation, which might
      regulate gene expression by affecting mRNA stability, mRNA transport, or
      translation initiation. The mechanisms behind deadenylation activation are highly
      regulated and associated with cellular conditions such as development, mRNA
      surveillance, DNA damage response, cell differentiation and cancer. After
      deadenylation, depending on the cellular response, some mRNAs might undergo an
      extension of the poly(A) tail or degradation. The polyadenylation/deadenylation
      machinery itself, miRNAs, or RNA binding factors are involved in the regulation
      of polyadenylation/deadenylation. Here, we review the mechanistic connections
      between polyadenylation and deadenylation and how the two processes are regulated
      in different cellular conditions. It is our conviction that further studies of
      the interplay between polyadenylation and deadenylation will provide critical
      information required for a mechanistic understanding of several diseases,
      including cancer development.

PMID- 21084876
TI  - Evaluating antimicrobial efficacy and cost of 3 dressings containing silver
      versus a novel antimicrobial hydrogel impregnated gauze dressing containing
      Oakin, an oak extract.
AB  - PURPOSE: Antimicrobial wound dressings are becoming more popular and are
      routinely used in the treatment of chronic and problematic wounds. Despite the
      ever-growing number and types of these antimicrobial products, many practitioners
      often do not report significant clinical differences between various common
      antimicrobial wound dressings despite wide variations in cost. Although these
      dressings use different active ingredients or different presentations of a
      particular active ingredient, all attempt to protect the wound from bacterial
      colonization and promote wound repair. With so many topical antimicrobial
      dressings to choose from in the clinical setting (many having already fallen into
      disfavor due to their cytotoxic characteristics) it was of prime interest to
      determine if there was a substantial difference between some of the more commonly
      used antimicrobial dressings, with silver versus an antimicrobial wound dressing
      using Oakin (oak extract [Amerx Health Care Corporation, Clearwater, Florida]) as
      the active ingredient. METHODS: This article compares the antimicrobial efficacy
      of 4 commonly used wound dressings in vitro, utilizing a corrected zone of
      inhibition test followed by a cost analysis. RESULTS: In vitro testing
      demonstrated that there were no substantial differences in the corrected zone of
      inhibition measurements between the silver wound dressings and the less expensive
      Oakin-impregnated gauze dressing. CONCLUSION: Despite obvious limitations of this
      study, these results suggest that the biggest differences between many
      antimicrobial dressings on the market may be more in cost than in antimicrobial
      efficacy. The differences in cost are due to variances in cost per application
      and frequency of applications per week.

PMID- 21084877
TI  - Symposium celebrates silver anniversary.

PMID- 21084878
TI  - Pressure ulcer prevalence and incidence in acute care.
AB  - OBJECTIVE: The objectives of the study were to identify the incidence and
      prevalence of pressure ulcers (PrUs) in acute-care patients, including the major
      contributing factors, and to modify existing policy and practices to align with
      the Institute for Healthcare Improvement recommendations for PrU prevention.
      DESIGN: In a cross-sectional, descriptive study, PrU prevalence was measured at
      quarterly intervals on predetermined days in 2009 using a standard data
      collection form. Incidence was measured 4 days later according to the facility's
      average length of stay. Patient demographics included age, sex, primary
      diagnoses, and contributing factors toward PrU development. PATIENTS: The study
      comprised adult medical, surgical, and intensive care patients in a northern
      California hospital. RESULTS: PrU prevalence ranged from 12% to 19.7%; incidence
      ranged from 0% to 5.4%. The most common PrU sites were heel (26%), coccyx (20%),
      and ear (19%). The major contributing factors were Braden score of less than 18
      (84%), serum albumin level of less than 3 (74%), fecal and/or urine incontinence
      (73%), fragile skin (67%), and bed bound (63%). CONCLUSION: This study supports
      the importance of collecting PrU prevalence and incidence data as an effective
      measure of nursing care and patient outcomes and to identify facility trends.

PMID- 21084879
TI  - Nutrition: a critical component of wound healing.
AB  - PURPOSE: To enhance the clinician's competence in using nutrition as an integral
      part of wound healing. TARGET AUDIENCE: This continuing education activity is
      intended for physicians and nurses with an interest in skin and wound care.
      OBJECTIVES: After participating in this educational activity, the participant
      should be better able to: 1. Analyze the effects of specific nutritional
      deficiencies and patient parameters on wound healing capabilities. 2. Accurately
      interpret laboratory values related to nutritional status. 3. Apply evidence
      based nutrition guidelines for improved wound healing.

PMID- 21084881
TI  - Incorporating competency checklists.

PMID- 21084882
TI  - Role of home blood pressure telemonitoring in hypertension management: an update.
AB  - Despite the increasing use of home blood pressure monitoring (HBPM) in daily
      practice and the growing awareness in the scientific community about its positive
      impact on the diagnostic and therapeutic management of patients with high blood
      pressure (BP), the potential advantages offered by HBPM have not yet been fully
      exploited. Indeed, use of the information offered by HBPM is often incomplete and
      imprecise, with the BP values reported by patients in handwritten logbooks being
      frequently inaccurate, illegible to physicians, or unreliable. Although a
      practical solution for improvement may come from the use of devices equipped with
      a storage memory, a step forward in this regard has been taken more recently with
      the introduction and refinement of systems for the remote telemonitoring of BP
      values measured at home. However, although several studies have provided evidence
      on the clinical usefulness of HBPM, only limited data are available on the
      clinical impact of home blood pressure (HBP) telemonitoring, because of a number
      of reasons. First, most of the available studies are characterized by a small
      sample size, and in some cases, the patients were neither randomized nor even
      matched with a control group. Moreover, technological solutions used in the
      different studies carried out so far are often heterogeneous, some of them being
      particularly difficult to use for the patients, thus limiting the effectiveness
      of the results. BP monitoring programmes, number of BP readings and transmission
      schedules are often different among the various studies. In addition, patient
      selection criteria are different from study to study. Finally, different study
      objectives and important diversities in the types of centres involved (ranging
      from general practices, to specialists' offices, hospitals or university centres)
      may have also influenced the quality of results. Large-scale randomized
      controlled studies, based on easy-to-use technologies, are thus still needed to
      show the superiority and clinical usefulness of HBP telemonitoring as compared
      with conventional HBPM. This study summarizes the evidence available on the
      clinical usefulness and current limitations of this approach, highlighting the
      results of meta-analyses and randomized controlled trials on this issue. The role
      of HBP teletransmission in the context of integrated patients' management
      programmes is also addressed, with indications for further progress in this
      field.

PMID- 21084883
TI  - Evidence-based architectural and space design supports Magnet(r) empirical
      outcomes.
AB  - This department expands nursing leaders' knowledge and competencies in health
      facility design. The editor of this department, Dr Jaynelle Stichler, asked guest
      authors, Drs Ecoff and Brown, to describe the process of using the conceptual
      models of a nursing evidence-based practice model and the Magnet Recognition
      Program(r) as a structured process to lead decision making in the planning and
      design processes and to achieve desired outcomes in hospital design.

PMID- 21084885
TI  - Hospital information technology systems' impact on nurses and nursing care.
AB  - OBJECTIVE: We conducted a review of the literature to determine the impact of
      health information technologies (HITs) on nurses and nursing care. BACKGROUND:
      Nurses' effective use of HIT has the potential to produce a positive impact on
      nursing-sensitive patient outcomes, patient safety, and quality of care. METHODS:
      A review of the literature produced 564 unique references of which 74 were
      selected for review. RESULTS: Findings suggest that (1) HIT improves the quality
      of nursing documentation; (2) HIT reduces medication administration errors; (3)
      nurses are generally satisfied with HIT and have positive attitudes about it; and
      (4) nurse involvement in all stages of HIT design and implementation, and
      effective leadership throughout these processes, can improve HIT. CONCLUSION: HIT
      has had positive influences on nurse satisfaction and patient care. Effective
      nursing leadership can positively influence the effective development,
      dissemination, and use of HIT.

PMID- 21084886
TI  - Primary Stroke Center education for nurses: improving core measures.
AB  - Primary Stroke Center designation by the Joint Commission distinguishes those
      healthcare organizations with exemplary stroke prevention and management.
      However, meeting the Joint Commission's high-level excellence standards is
      challenging. This article provides nurse leaders with a stroke education
      template, based on Donabedian's quality model, which meets Primary Stroke Center
      nurse education requirements. The authors describe the structure, process, and
      outcomes of a stroke education program for nurses, recognized as Best-in-Practice
      in Connecticut, successfully implemented in a community hospital.

PMID- 21084887
TI  - Virtual journal club connects evidence to practice: an analysis of participant
      responses.
AB  - Advancing evidence-based practice in hospitals can be a challenge. To address
      this issue, a virtual journal club (VJC) was developed using available intranet
      technology. Research manuscripts are posted along with professional critiques and
      discussion questions. Comments from nurse VJC participants are reviewed by the
      hospital's nursing research council and analyzed for practice implications.
      Recommendations for practice change derived from the analysis are forwarded to
      the appropriate decision-making body for consideration. This process closes the
      loop ensuring that the VJC not only exposes the nursing staff to scientific
      evidence to support changing their practice but also may lead to institutional
      policy changes that are based on best practice evidence in the literature. The
      authors discuss the VJC and the outcomes of an evaluation project.

PMID- 21084888
TI  - Advancing the education of nurses: a call for action.
AB  - The debate over the educational preparation of RNs has raged for over a century.
      In New York, chief nursing officers are partnering with academic colleagues and
      successfully implementing a model that standardizes education requirements,
      supports seamless transition from associate to baccalaureate degree programs,
      addresses financial barriers, and identifies expected outcomes of a more educated
      workforce. Nursing leaders are perfectly positioned to advance the educational
      standards of the profession in the United States.

PMID- 21084889
TI  - Actions, behaviors, and characteristics of RNs involved in compensable injury.
AB  - Malpractice claims analysis offers valuable insight into nursing practice. A
      review of 16 malpractice claims involving 19 RNs identified their
      characteristics, actions, and behaviors that contributed to monetary
      compensation. Most events involved failure to perform a timely assessment and
      intervention. Relationships were found among nurses' characteristics and the
      severity of patient injury. Malpractice claims analysis affords nursing leaders
      the opportunity to involve RNs in correcting deficiencies that contribute to
      practice errors.

PMID- 21084890
TI  - A patient-centered model to improve metrics without cost increase: viewing all
      care through the eyes of patients and families.
AB  - The need for patient-centeredness in care delivery has been articulated for
      decades, yet meaningful progress toward patient-centered healthcare has been
      hobbled by the lack of a replicable patient-centered care model and method. The
      authors describe the patient- and family-centered care method, built around
      viewing every care experience through the eyes of the patient and family, and its
      outcomes proving the approach is replicable and sustainable while improving
      outcomes without additional cost. A follow-up article on patient and family
      shadowing will be published in the January 2011 issue.

PMID- 21084891
TI  - Lessons in innovation: role transition experiences of clinical nurse leaders.
AB  - OBJECTIVE: The purpose of this study was to describe the role transition
      experiences of 71 Clinical Nurse Leaders (CNLs) as they pioneered the role in
      practice settings. BACKGROUND: Although the impact of CNL practice is now being
      measured through a variety of evaluation projects, less is known about the role
      transition experiences of CNLs. METHODS: This was a qualitative study using an
      interpretative phenomenological analysis approach. Semistructured telephone
      interviews were conducted with 71 CNLs working in the role. RESULTS: The 5 major
      themes that emerged from the study included staying at the bedside, explaining
      who we are, keeping things from falling through the cracks, and proving our value
      and cautious about the future. CONCLUSION: The results of the study can both help
      to inform nurse leaders about introducing major changes in their organizations
      and guide future CNLs in their role transition.

PMID- 21084892
TI  - Risk of brain tumors from wireless phone use.
AB  - The debate regarding the health effects of low-intensity electromagnetic
      radiation from sources such as power lines, base stations, and cell phones has
      recently been reignited. Wireless communication has dramatically influenced our
      lifestyle; its impact on human health has not been completely assessed.
      Widespread concern continues in the community about the deleterious effects of
      radiofrequency radiations on human tissues and the subsequent potential threat of
      carcinogenesis. Exposure to low-frequency electromagnetic field has been linked
      to a variety of adverse health outcomes. This article surveys the results of
      early cell phone studies, where exposure duration was too short to expect tumor
      genesis, and 2 sets of more recent studies with longer exposure duration: the
      Interphone studies and the Swedish studies led by Hardell.

PMID- 21084893
TI  - Diffusion-weighted magnetic resonance imaging of head and neck.
AB  - Our aim was to review the clinical applications of diffusion-weighted magnetic
      resonance imaging in the head and neck. Diffusion-weighted magnetic resonance
      imaging plays a role in the differentiation of benign from malignant head and
      neck tumors, squamous cell carcinoma from lymphoma, and metastatic from benign
      lymphadenopathy as well as in the selection of the biopsy site. It can be used
      for the differentiation of recurrent tumors from posttreatment changes and in
      monitoring the patient after radiotherapy. It helps in the differentiation of
      necrotic tumors from abscesses. Additionally, it can be used for the diagnosis
      and grading of diffuse autoimmune diseases, such as Sjogren and Graves diseases.

PMID- 21084894
TI  - Automatic bone removal dual-energy CT angiography for the evaluation of
      intracranial aneurysms.
AB  - PURPOSE: To evaluate the diagnostic accuracy of dual-energy computed tomographic
      angiography (DE-CTA) in the detection of intracranial aneurysms and to determine
      whether DE-CTA provides adequate information to guide treatment choice. MATERIALS
      AND METHODS: Eighty patients (31 men and 49 women; mean [SD] ages of 52 [9]
      years) with spontaneous subarachnoid hemorrhage underwent DE-CTA. The performance
      of DE-CTA was compared with conventional CTA created from average weighted images
      and digital subtraction angiography (DSA). Sensitivity and specificity for
      aneurysm detection were determined on a per-patient and per-aneurysm basis. The
      treatment choice was assessed on the basis of aneurysm neck size and/or the
      dome/neck ratio. RESULTS: With DSA as reference standard (n = 61; 47 aneurysms in
      41 patients), DE-CTA correctly detected 45 aneurysms in 41 patients corresponding
      to sensitivity and specificity of 100% and 95.0% on a per-patient basis versus
      95.7% and 95.0% on a per-aneurysm basis, whereas conventional CTA correctly
      detected 43 aneurysms in 39 patients corresponding to sensitivity and specificity
      of 95.1% and 95.0% on a per-patient basis versus 91.5% and 95.0% on a per
      aneurysm basis. No statistical difference between DE-CTA and conventional CTA was
      found for the diagnostic evaluation of intracranial aneurysms. Surgery was
      performed to treat 38 aneurysms, coiling in 26 aneurysms, stent in one patient,
      and follow-up in the remaining 5 aneurysms. Dual-energy CTA correctly predicted
      treatment choice in 44 aneurysms, with 15 aneurysms coiled and 29 aneurysms
      clipped. CONCLUSIONS: Compared with DSA, DE-CTA had a comparable diagnostic
      accuracy for the detection of intracranial aneurysms, visualization of the
      morphology of aneurysms at the skull base, and prediction of aneurysm treatment
      choice in most patients with spontaneous subarachnoid hemorrhage based on this
      study.

PMID- 21084895
TI  - Magnetic resonance dynamic susceptibility-weighted contrast-enhanced perfusion
      imaging in the diagnosis of posterior fossa hemangioblastomas and pilocytic
      astrocytomas: initial results.
AB  - OBJECTIVE: The purpose of this study was to compare the dynamic susceptibility
      weighted contrast-enhanced (DSC) magnetic resonance (MR) perfusion and MR imaging
      findings between hemangioblastomas and pilocytic astrocytoma (PA). METHODS: We
      retrospectively identified 6 patients with hemangioblastomas and 8 patients with
      PAs who underwent MR imaging before resection. Using fluid-attenuated inversion
      recovery imaging, we graded peritumoral edema as absent, minimal, mild, moderate,
      or severe. In addition, 3 patients with hemangioblastomas and 4 patients with PAs
      underwent DSC-MR imaging before resection. RESULTS: We observed moderate to
      severe peritumoral edema in 6 patients with hemangioblastomas and none or minimal
      peritumoral edema in 8 patients with PAs. The mean relative cerebral blood volume
      was 7.7 (SD, 1.0) in patients with hemangioblastomas and 1.8 (SD, 1.8) in
      patients with PAs. CONCLUSIONS: Our preliminary findings demonstrate
      significantly higher DSC-MR imaging relative cerebral blood volumes in patients
      with hemangioblastomas when compared with patients with PAs. In addition,
      moderate to severe peritumoral edema was associated with hemangioblastomas.

PMID- 21084896
TI  - Whole-brain perfusion measurement using 320-detector row computed tomography in
      patients with cerebrovascular steno-occlusive disease: comparison with 15O
      positron emission tomography.
AB  - OBJECTIVE: The 320-detector row computed tomography (CT) can provide whole-brain
      CT perfusion (CTP) maps with continuous angiographic images by performing a
      single dynamic scan. We investigated the reliability of CTP cerebral blood flow
      (CTP-CBF) with 320-detector row CT by comparing findings with O-positron emission
      tomography (PET-CBF). METHODS: Whole-brain CTP and PET were performed in 10
      patients with chronic unilateral steno-occlusive disease. We compared absolute
      and relative CBF values of bilateral middle cerebral artery territories between
      CTP and PET. RESULTS: Although mean CTP-CBF values were approximately 30% lower
      than mean PET-CBF values, the mean ischemic-to-nonischemic CBF ratios of CTP and
      PET were almost identical (P = 0.804). Regression analysis showed a significant
      correlation between CTP-CBF and PET-CBF values for each patient (r = 0.52-0.85, P
      < 0.001). CONCLUSIONS: Whole-brain CTP using 320-detector row CT is useful for
      evaluating the degree of ischemia for the entire brain with chronic
      cerebrovascular disease.

PMID- 21084897
TI  - Proton magnetic resonance spectroscopy in differentiating glioblastomas from
      primary cerebral lymphomas and brain metastases.
AB  - OBJECTIVE: To differentiate glioblastomas, primary cerebral lymphomas (PCLs), and
      brain metastases using multivoxel proton magnetic resonance (MR) spectroscopic
      imaging. METHODS: A total of 56 patients with brain neoplasms underwent MR
      imaging and proton MR spectroscopic imaging. The data were analyzed from contrast
      enhancing and peritumoral regions (PTR). N-acetylaspartate/creatine (Cr), choline
      (Cho)/Cr, glutamate+glutamine/Cr, myo-inositol/Cr, and lipids+lactate/Cr ratios
      were computed, and pairwise comparisons between neoplasms were made using Mann
      Whitney U tests. RESULTS: The PTR demonstrated most significant differences in
      metabolite ratios. The Cho/Cr ratio in glioblastomas (0.46 [0.01]) was
      significantly higher than that in metastases (0.38 [0.02], P = 0.01).
      Significantly elevated Cho/Cr levels were also noted in PCLs (0.48 [0.03])
      compared with those in metastases (P = 0.04). In addition, PCLs also demonstrated
      significantly higher lipids+lactate/Cr levels (11.83 [2.59]) compared with
      glioblastomas (4.50 [0.59], P = 0.003) and metastases (2.79 [0.33], P = 0.001).
      CONCLUSIONS: Proton MR spectroscopic imaging from PTR may assist in the
      differentiation of glioblastomas, metastases, and PCLs.

PMID- 21084898
TI  - Echocardiogram-gated computed tomographic and magnetic resonance angiographies
      for the detection of pulsatile expansion at the intracranial arterial
      bifurcation.
AB  - OBJECTIVE: To identify the pulsatile small vascular lesion by echocardiogram
      (ECG)-gated computed tomographic (CT) and magnetic resonance (MR) angiographies.
      METHODS: Seven patients who exhibited small evagination at the cerebral artery
      bifurcations on 3-dimensional (3D) time-of-flight MR angiogram were enrolled.
      They were examined by conventional/ECG-gated CT angiogram (n = 6) and ECG-gated
      MR angiogram (n = 5). Echocardiogram-gated MR angiogram was performed with 3D
      time of flight, triggered after each time window. From ECG-gated CT and MR
      angiograms, consecutive 10-phase images within a single cardiac cycle were
      obtained. RESULTS: The pulsatile change of evagination was demonstrated on both
      ECG-gated CT angiogram (5 of 6 patients) and ECG-gated MR angiogram (all 5
      patients). Flattening of the evagination during the diastolic phase was observed
      in 4 of 6 ECG-gated CT angiograms and 3 of 5 ECG-gated MR angiograms. Of note was
      a patient with a tiny evagination (<2 * 1 mm); pulsatile change was demonstrated
      only by ECG-gated MR angiogram. CONCLUSION: The pulsatile expansion of
      evagination at the cerebral artery bifurcation can be demonstrated on ECG-gated
      CT/MR angiograms.

PMID- 21084899
TI  - Differentiation of Bosniak categories IIF and III cystic masses: what
      radiologists should know.
AB  - Based on a review of the literature, we describe old and new features that both
      old and new radiologists should be aware of (a) to determine which imaging
      features affect the differentiation of categories IIF and III masses, (b) to show
      imaging features of benign cystic renal masses preoperatively diagnosed as
      category III, and (c) to introduce imaging techniques that help to differentiate
      categories IIF and III masses without requiring the use of CT or magnetic
      resonance contrast material.

PMID- 21084900
TI  - Role of magnetic resonance imaging as an adjunct to clinical staging in cervical
      carcinoma.
AB  - Magnetic resonance imaging depicts the morphological details of the female pelvis
      and is useful for evaluating both benign and malignant cervical masses. Clinical
      assessment of the extent of cervical cancer is crucial in determining the optimal
      treatment strategy, but clinical staging by itself has limitations. Clinical
      staging, as defined by FIGO (International Federation of Gynecologic Oncology),
      is based on the findings of physical examination, lesion biopsies, chest
      radiography, cystoscopy, and renal sonography and can be erroneous, depending on
      the stage of the disease, by 16% to 65%. The prognosis of cervical cancer is
      determined not only by stage, but also by nodal status, tumor volume, and depth
      of invasion, none of which are included in the FIGO guidelines. Magnetic
      resonance imaging has been described as the most accurate, noninvasive imaging
      modality in staging cervical carcinoma. This review outlines the magnetic
      resonance features of normal cervix, primary disease (by stage), and recurrent
      disease and discusses the role of magnetic resonance imaging in staging and
      clinical decision making.

PMID- 21084901
TI  - Magnetic resonance imaging of massive ovarian edema in pregnancy.
AB  - OBJECTIVE: To investigate the MRI findings of massive ovarian edema in pregnancy.
      CONCLUSIONS: Asymmetric ovarian enlargement with a teardrop configuration and T2
      hyperintensity with or without T1 hyperintensity appear characteristic of massive
      ovarian edema in pregnancy, potentially facilitating nonoperative diagnosis and
      expectant management. These findings support the concept that massive ovarian
      edema in pregnancy reflects chronic partial ovarian torsion.

PMID- 21084902
TI  - Gd-EOB-DTPA-enhanced magnetic resonance imaging findings of nondiffuse fatty
      change of the liver.
AB  - PURPOSE: To evaluate the difference in enhancement effects between the area of
      fatty change and the area of nonfatty change in patients with nondiffuse fatty
      change of the liver at gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic
      acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging. METHODS: Thirteen
      patients with nondiffuse fatty change of the liver underwent Gd-EOB-DTPA-enhanced
      MR imaging including dynamic study using a 1.5-T MR unit. Dynamic contrast
      enhanced (DCE) MR images were obtained at pre, arterial phase (25 seconds),
      portal phase (70 seconds), equilibrium phase (3 minutes), and hepatobiliary phase
      (10, 15, 20 minutes). The percentage differences of signal enhancement ratio were
      calculated from signal intensity measurement of the liver in each phase of DCE
      study and were compared between the area of fatty change and the area of nonfatty
      change in all phases. RESULTS: In the all phases on DCE study, there were no
      significant differences in the signal enhancement ratio between the area of fatty
      change (27.7% +/- 14.8%, 58.2% +/- 14.7%, 62.7% +/- 10.6%, 80.4% +/- 15.2%, 84.9%
      +/- 16.2%, 88.0% +/- 14.3%) and the area of nonfatty change (29.9% +/- 16.6%,
      54.9% +/- 13.3%, 63.0% +/- 8.8%, 75.7% +/- 12.6%, 80.3% +/- 15.7%, 86.4% +/-
      14.5%) (P = 0.613). CONCLUSIONS: Although our results are limited by the small
      number of patients, our results showed that the presence of fatty change of the
      liver did not affect the hepatic contrast enhancement effects of Gd-EOB-DTPA in
      all phases on dynamic study. This indicates that Gd-EOB-DTPA may be a reliable
      marker to identify areas of nondiffuse fatty change of the liver.

PMID- 21084903
TI  - An optimal contrast dose indicator for the determination of hepatic enhancement
      in abdominal multidetector computed tomography: comparison of patient attenuation
      indicator with total body weight and body mass index.
AB  - PURPOSE: To evaluate a patient attenuation indicator (PAI) as compared with
      traditional patient-related factors of total body weight and body mass index
      (BMI) as a predictor of hepatic enhancement in contrast-enhanced abdominal
      multidetector computed tomography (MDCT). MATERIALS AND METHODS: Institutional
      review board approval was obtained, and the study was Health Insurance
      Portability and Accountability Act compliant. A total of 77 patients (mean age,
      53 years; male-female ratio, 32:45) underwent routine contrast-enhanced abdominal
      CT on a 16-slice multidetector CT (LightSpeed 16; GE Medical Systems, Milwaukee,
      Wis). Contrast enhancement was achieved by administering a 120-mL iodine contrast
      medium (350-mg iodine per milliliter) at an injection rate of 3 mL/s followed by
      an injection of 40-mL saline at 3 mL/s. Computed tomographic attenuation values
      (Hounsfield units [HU]) of liver parenchyma, main portal vein, and abdominal
      aorta were measured in each patient. Statistical analysis was performed with
      linear regression to determine the correlation of PAI, total body weight, and BMI
      with abdominal organ enhancement. RESULTS: The mean of PAI, total body weight,
      and BMI were 28.0 (range, 22.1-34.2), 79.0 kg (range, 49.6-112.2 kg), and 27.5
      kg/m (range, 16.8-43 kg/m), respectively. Mean hepatic enhancement was 128.2 HU
      (range, 73.6-175 HU), mean main portal vein enhancement was 214.2 HU (range, 118
      327 HU), and mean abdominal aorta enhancement was 208.9 HU (range, 116-395 HU).
      Patient attenuation indicator, total body weight, and BMI showed a negative
      correlation with liver enhancement (r = -0.55, r = -0.4, and r = -0.3,
      respectively). Patient attenuation indicator exhibited a significantly higher
      correlation with hepatic enhancement than total body weight and BMI (P < 0.01,
      respectively). CONCLUSIONS: Patient attenuation indicator exhibits a moderately
      inverse correlation with liver enhancement that is greater than those of total
      body weight and BMI. Patient attenuation indicator may be reliable in predicting
      the hepatic enhancement degree for a given dose of contrast material and has a
      potential use in customizing individual patient contrast medium dose during
      contrast-enhanced abdominal CT.

PMID- 21084904
TI  - Sensitivity of digital abdominal radiography for the detection of ureter stones
      by stone size and location.
AB  - OBJECTIVE: To assess the sensitivity of digital abdominal radiography in the
      detection of ureteral stones by stone size and location. MATERIALS AND METHODS:
      We retrospectively reviewed the digital abdominal radiography of 163 patients for
      the detection of ureteral stones. Each ureteral stone was confirmed by unenhanced
      computed tomography (CT) in the emergency department between January and
      December, 2009. Stone location was defined as proximal or distal by the level
      where the ureter crossed anterior to iliac vessels, and the stone size was
      defined as small if smaller than 5 mm and large if larger than 5 mm on unenhanced
      CT. The interpretation of digital abdominal radiography was classified as
      visible, invisible, or equivocal. RESULTS: In 163 ureteral stones, 77 stones
      (47.2%) were in the proximal ureter and 86 stones (52.8%) were in the distal
      ureter. The mean (SD) size of the ureteral stones was 3.4 (1.7) mm (range, 1-9
      mm). Overall sensitivity of digital radiography for ureteral stones was 29.4%.
      The sensitivity of digital radiography for the proximal ureteral stones was 37.7%
      and that for the distal ureteral stones was 22.1% (P < 0.05). The sensitivity of
      digital radiography for small ureteral stones was 23.6% and that for large
      ureteral stones was 50.0% (P < 0.05). As a group, the sensitivity of digital
      radiography for large proximal ureteral stones was the highest sensitivity-72.2%
      in all groups (P < 0.05). CONCLUSION: Digital abdominal radiography is useful in
      detecting large proximal ureteral stones.

PMID- 21084905
TI  - Sixty-four-multidetector-row computed tomography angiography with bolus tracking
      to time arterial-phase imaging in healthy liver: is there a correlation between
      quantitative and qualitative scores?
AB  - PURPOSE: To determine the optimal 64-multidetector-row computed tomography scan
      delay from bolus-tracking trigger for the arterial phase and the evaluation of
      vascularization in healthy liver. MATERIALS AND METHODS: One hundred twenty
      patients are randomized into 3 groups according to scan delay (5-, 10-, 15-second
      arterial phase) and underwent CT of the liver. Images were evaluated on the basis
      of quantitative and qualitative scores. A correlation analysis between them was
      managed to find the most effective scan delay for best radiologists'
      diagnostically performances. RESULTS: Scanning too early results in images that
      are acquired before the vascular peak enhancement while scanning to late results
      in the increasing of liver parenchyma portal feeding. Good performances were
      obtained with a scan delay ranging between 10 and 19 seconds from the trigger.
      CONCLUSIONS: When a 64-multidetector-row computed tomography with a bolus
      tracking program is used, only 1 arterial phase should be acquired, setting a
      scan delay of 10 to 19 seconds.

PMID- 21084906
TI  - Cytomegalovirus enterocolitis in apparently immunocompetent hosts: evaluation of
      the radiologic findings and clinical features.
AB  - OBJECTIVE: To describe the clinical and radiologic features of cytomegalovirus
      (CMV) enterocolitis in apparently immunocompetent hosts. MATERIALS AND METHODS:
      Our institutional review board approved this retrospective study, and informed
      consent was waived. Twelve apparently immunocompetent patients (7 women and 5
      men; mean age, 58 years) with pathologically proven CMV enterocolitis were
      included. Computed tomographic (CT) scans were retrospectively reviewed to
      determine the extent and the location of mural thickening, maximal mural
      thickness, enhancement pattern, that is, single-halo, double-halo, and
      homogeneous patterns, and ascites. RESULTS: Eight patients had comorbidities
      potentially affecting the host immune status, whereas 4 patients were apparently
      healthy before presentation. On CT, all patients showed mural thickening (range,
      4-11 mm) involving the colon (n = 8), the small bowel (n = 1), or both (n = 3).
      Segmental involvement was most common (n = 9 for colon and n = 2 for small
      bowel), whereas focal involvement of the rectum (n = 1) and diffuse involvement
      of the entire ileum (n = 1) or the entire small bowel and colon (n = 1) were also
      noted. Colonic lesions showed variable enhancement patterns, including the single
      halo (n = 6), homogeneous (n = 3), and double-halo patterns (n = 2), whereas all
      small-bowel lesions in 4 patients exhibited a single-ring pattern. Ascites was
      present in 7 patients. Complications requiring surgery occurred in 3 patients and
      included refractory bleeding (n = 2) and bowel perforation (n = 1). CONCLUSIONS:
      Cytomegalovirus enterocolitis in immunocompetent hosts typically develops in
      elderly subjects with comorbidities, although it may also affect relatively young
      and healthy subjects. On CT, it is characterized by mild mural thickening of the
      small bowel and the colon and frequently shows segmental involvement and a single
      halo enhancement pattern.

PMID- 21084907
TI  - Added value of multiplanar reformations to axial multi-detector row computed
      tomographic images for the differentiation of macrocystic pancreas neoplasms:
      receiver operating characteristic analysis.
AB  - PURPOSE: To retrospectively assess the added value of multiplanar reformations
      (MPR) to axial multi-detector row computed tomographic (MDCT) images in
      differentiating macrocystic pancreas neoplasms. MATERIALS AND METHODS: Approval
      from the institutional review board was obtained. Two radiologists
      retrospectively reviewed axial CT images of 48 pathologically proven pancreas
      macrocystic neoplasms with and without MPRs. They were asked to determine the
      presence of pancreatic duct (PD) communication with the lesions and whether the
      lesion is an intraductal papillary mucinous neoplasm (IPMN) or not on a 5-point
      confidence scale and to record the specific diagnoses and their confidence.
      Radiologists' performances for determining PD communication and lesion
      differentiation using axial CT with and without MPRs were evaluated using
      receiver operating characteristic analysis. To determine the accuracy of the
      specific diagnoses, Fisher exact and Mann-Whitney U tests were used.
      Interobserver agreement was also analyzed. RESULTS: With the addition of MPRs,
      receiver operating characteristic analysis revealed a tendency toward improved
      determination of PD communication and better differentiation between IPMN and non
      IPMN. However, a significant difference was found only in reviewer 2 for the
      determination of PD communication (P = 0.009). Diagnostic accuracy of specific
      diagnoses was also improved; however, the differences were not significant.
      Specific diagnoses were more confidently made with the addition of MPRs than with
      axial images alone, and a significant difference was seen for reviewer 2 (P <
      0.001). Furthermore, substantial interobserver agreement was achieved with the
      addition of MPRs, whereas fair or substantial agreement was noted with axial
      images alone. CONCLUSIONS: The addition of MPRs to axial CT images may improve
      diagnostic performance and decrease interobserver variability of MDCT for the
      determination of PD communication with macrocystic pancreatic neoplasms and
      differentiation between IPMN and non-IPMN.

PMID- 21084908
TI  - Computed tomography criterion for the diagnosis of appendicitis without
      periappendiceal inflammation in children using the maximum depth of intraluminal
      appendiceal fluid.
AB  - OBJECTIVE: The objective of this study was to evaluate whether maximum depth of
      intraluminal appendiceal fluid (DEPTH) is useful in differentiating appendicitis
      without periappendiceal inflammation from enlarged normal appendices in children.
      METHODS: We retrospectively evaluated 826 intravenously enhanced abdominal-pelvic
      computed tomographic examinations in children (aged 0-18 years) using the
      following criteria for appendicitis: (1) appendiceal wall thickness greater than
      3 mm, (2) appendiceal wall enhancement, (3) focal cecal wall thickening, (4)
      adjacent adenopathy, (5) appendicolith, and (6) DEPTH. Of 826, 192 were
      classified into the noncomplicated-normal appendix group (85 enlarged normal
      appendices [diameter >6 mm] without adjacent lesions), the complicated-normal
      appendix group (44 enlarged normal appendices with adjacent lesions), or the our
      appendicitis group (63 operatively proved appendicitis without periappendiceal
      inflammation). RESULTS: The criterion "DEPTH greater than 2.6 mm" determined by
      receiver operating characteristic analysis between our-appendicitis and
      complicated-normal appendix groups demonstrated both higher sensitivity and
      higher specificity in all groups (>90%). In contrast, the other criteria showed
      lower sensitivities (<58%) in our-appendicitis group. CONCLUSIONS: The criterion
      "DEPTH greater than 2.6 mm" is particularly useful for differentiating
      appendicitis without periappendiceal inflammation from enlarged normal appendices
      in children.

PMID- 21084909
TI  - MRI findings of angiomyolipoma of the renal sinus in 5 cases.
AB  - The magnetic resonance imaging (MRI) appearance of 5 cases of angiomyolipoma
      (AML) centered in the renal sinus is presented. All cases exhibited similar
      imaging findings, including well-circumscribed margins, minimal perceived
      enhancement without soft tissue components, insinuation around the renal
      collecting system, and localized hydrocalicosis with associated localized renal
      parenchymal atrophy but without generalized hydronephrosis. Findings in some
      cases included extension out of the renal sinus and presence of aneurysmal
      vessels. Although identification of a renal parenchymal defect has been reported
      to be useful for the differentiation of a large exophytic AML from a perirenal
      liposarcoma, none of the cases in our series demonstrated this finding on MRI. To
      our knowledge, there have been only 2 previous reported cases showing the cross
      sectional imaging appearance of an AML of the renal sinus without a renal
      parenchymal defect. In view of the shared and characteristic imaging features of
      the 5 cases in our series, we believe that the diagnosis of this condition can be
      strongly suggested by MRI despite the absence of a visible parenchymal defect.
      While histology remains the only way to definitively establish the diagnosis, the
      typical imaging appearance of this entity should enable conservative management
      with follow-up imaging in an asymptomatic patient. In some cases, embolization
      and needle biopsy could be used to avoid a surgical approach.

PMID- 21084910
TI  - In vivo assessment of coronary stents with 64-row multidetector computed
      tomography: analysis of metal artifacts.
AB  - OBJECTIVE: To evaluate stent-induced artifacts by 64-row multidetector computed
      tomography (MDCT). METHODS: We studied 26 stented patients with MDCT before
      conventional coronary angiography (CCA). The CT values were measured. Stents were
      classified as occluded, with significant stenosis, with nonsignificant stenosis,
      or patent. For the patent stents, mean in-stent and out-stent CT values were
      compared; stents 3 mm or smaller were compared with stents larger than 3 mm.
      Multidetector CT was compared with CCA. RESULTS: We analyzed 42 stents. At CCA,
      34 stents were patent, 5 were nonsignificantly stenosed, 1 was significantly
      stenosed, and 2 were occluded. At MDCT, 33 of 34 patent stents, 2 occluded
      stents, and 1 stent with significant stenosis were correctly diagnosed;
      nonsignificant stenoses were undetected, 1 patent stent was misdiagnosed as
      occluded (kappa = 0.727). The out-stent CT value was lower than in-stent CT value
      both in stents 3 mm or smaller (P = 0.001) and stents larger than 3 mm (P <
      0.001). The in-stent CT value of stents 3 mm or smaller was higher (P = 0.011)
      than that of stents larger than 3 mm. CONCLUSIONS: Metal artifacts cause
      overlooking of nonsignificant stenosis.

PMID- 21084911
TI  - Streptococcus milleri group pleuropulmonary infection in children: computed
      tomographic findings and clinical features.
AB  - OBJECTIVE: Streptococcus milleri group streptococci have recently been
      increasingly recognized as important pulmonary pathogens, but their imaging
      features have not been well documented in children. We have recently observed a
      number of cases of this infection among pediatric patients at our tertiary care,
      children's hospital. Our purpose was to investigate the computed tomographic (CT)
      findings and clinical features of S. milleri group pleuropulmonary infection in
      children. MATERIALS AND METHODS: We used our hospital information system to
      identify all consecutive pediatric patients (<18 years of age) who had both a
      microbiologically proven S. milleri group infection and a chest CT scan between
      December 1996 and May 2009. Each scan was systemically reviewed by 2 pediatric
      radiologists for pleural and lung parenchymal abnormalities. Pleural effusions
      were classified as either simple or complex and correlated with results of
      pleural fluid analysis. Computed tomographic findings were compared with chest
      radiographic findings in the subset of patients who underwent radiography within
      24 hours of CT. Microbiological data, risk factors, immune status, patient
      management, and clinical outcome were systematically reviewed. RESULTS: The final
      study cohort consisted of 15 children (6 boys and 9 girls), ranging in age from
      4.2 years to 17.7 years (mean, 10.8 years). All patients were immunocompetent
      without recognized risk factors for this infection. Thirteen pleural effusions
      were identified in 10 (67%) of the 15 patients, including 10 complex and 3 simple
      pleural effusions. All complex effusions at CT were consistent with empyemas by
      pleural fluid analysis. Lung parenchymal abnormalities were identified in 7 (47%)
      of the 15 patients, including lung abscess in 4 patients, consolidation in 2, and
      multiple bilateral pulmonary nodules and lung abscesses in 1. In the subset of 7
      patients with comparison radiographs, radiographic and CT findings were
      concordant for the detection of lung abnormalities, except one case in which
      consolidation was diagnosed on chest radiography, whereas CT scan showed a lung
      abscess. Radiographs detected all 4 complex pleural effusions seen on CT scan,
      although it was not possible to characterize the effusions as simple or complex
      on the radiographs. Interventional procedures were required in all 15 patients,
      most commonly thoracentesis (n = 11) and chest tube drainage (n = 9).
      CONCLUSIONS: In children with S. milleri group pleuropulmonary infection, CT
      often demonstrates complex pleural effusions and lung abscesses, which usually
      require interventional procedures for effective treatment.

PMID- 21084912
TI  - Repeated low-dose computed tomography in current and former smokers for
      quantification of emphysema.
AB  - OBJECTIVE: To quantify different emphysema evolution in current and former
      smokers. METHODS: We retrospectively analyzed low-dose computed tomography scans
      from a lung cancer screening study of 59 current and 75 former smokers. The
      quantitative emphysema analysis was performed using a home-built software (YACTA
      version 0.9), yielding the parameters lung volume, emphysema volume (EV),
      emphysema index (EI), mean lung density, and 15th percentile. RESULTS: The
      baseline EV and EI were significantly different (median EVformer =422 mL vs
      EVcurrent =249 mL, P = 0.0003; and median EIformer =7.6 % vs EIcurrent =4.1 %, P
      = 0.0001, respectively). On the annual repeat scan, the median EI and EV for
      former smokers had decreased significantly (DeltaEIformer = -0.257%, P = 0.004;
      and DeltaEVcurrent = -0.203 mL, P = 0.020), whereas there was no emphysema change
      in current smokers. CONCLUSIONS: We were able to demonstrate different emphysema
      evolution in current versus former smokers; emphysema parameters decreased in the
      former smokers and remained stable in current smokers.

PMID- 21084913
TI  - Demonstration of the anatomy of the esophageal artery using multidetector-row
      helical computed tomography.
AB  - OBJECTIVE: To assess the ability of multidetector-row helical computed tomography
      to depict the esophageal artery. METHODS: Patients with esophageal cancer (n =
      88) underwent multidetector-row helical computed tomography. Degree of
      visualization, branching level, angle, and length of the esophageal artery were
      investigated. RESULTS: In 79 (89.8%) of 88 patients, a total of 146 esophageal
      arteries were delineated from the origin to the insertion into the esophagus. Of
      the 146 arteries, 112 (76.7%) originated from the descending aorta and 34 (23.3%)
      from the right intercostal artery. Of the 112 aorta-originated arteries, 110
      (98.2%) originated at a level between T6 and T11 from the left side of the
      descending aorta to go into the left wall of the esophagus. Of the 34 intercostal
      originated arteries, 27 (79.4%) originated from right intercostal arteries
      between T5 and T7 to go into the esophagus. CONCLUSIONS: Multi-detector-row
      helical computed tomography depicted the esophageal artery in a high percentage
      of the patients.

PMID- 21084914
TI  - Chronic beryllium disease: computed tomographic findings.
AB  - Chronic beryllium disease is a rare multisystem granulomatous disease
      predominantly involving the lungs and resulting from an immunologic response to
      long-term occupational exposure. Computed tomography of the chest reveals
      important lung parenchymal and mediastinal findings and plays an important role
      in the diagnosis and follow-up assessment of patients with chronic beryllium
      disease. Its significance lies in the exact localization and evaluation of the
      extent of lesions. We present an overview of the subject and a pictorial review
      of the spectrum of computed tomographic features of beryllium disease.

PMID- 21084915
TI  - Texture analysis, bone mineral density, and cortical thickness of the proximal
      femur: fracture risk prediction.
AB  - OBJECTIVE: The objectives of this study were to perform a clinical study
      analyzing bone quality in multidetector computed tomographic images of the femur
      using bone mineral density (BMD), cortical thickness, and texture algorithms in
      differentiating osteoporotic fracture and control subjects; to differentiate
      fracture types. METHODS: Femoral head, trochanteric, intertrochanteric, and upper
      and lower neck were segmented (fracture, n = 30; control, n = 10). Cortical
      thickness, BMD, and texture analysis were obtained using co-occurrence matrices,
      Minkowski dimension, and functional and scaling index method. RESULTS: Bone
      mineral density and cortical thickness performed best in the neck region, and
      texture measures performed best in the trochanter. Only cortical thickness and
      texture measures differentiated femoral neck and intertrochanteric fractures.
      CONCLUSIONS: This study demonstrates that differentiation of osteoporotic
      fracture subjects and controls is achieved with texture measures, cortical
      thickness, and BMD; however, performance is region specific.

PMID- 21084916
TI  - Isolated bone infarct of the calcaneus after fracture.
AB  - The calcaneus has a rich vascular supply; therefore, avascular necrosis of the
      calcaneus is extremely rare. We report the first case of bone infarct of the
      calcaneus 9 months after a fracture. We also review the literature on
      osteonecrosis of the calcaneus to offer potential mechanisms for bone infarction
      in the calcaneus after a fracture.

PMID- 21084917
TI  - Arterial anatomy of the pancreas. Part 3: segmented computed tomography
      angiography mapping of perineural invasion.
AB  - This is the third in a series of medical graphics articles featuring the arterial
      anatomy of the pancreas as depicted on segmented computed tomography-angiography.
      These segmented computed tomography-angiography displays serve as a road map of
      the routes of tumor spread by ductal adenocarcinoma of the pancreas because
      perineural tumor invasion parallels the pancreatic arteries.

PMID- 21084919
TI  - PROFILE PD: profile of function and impairment level experience with Parkinson
      disease--clinimetric properties of a rating scale for physical therapist
      practice.
AB  - BACKGROUND AND PURPOSE: Individuals with Parkinson disease (PD) experience a
      range of deficits of body systems and activities. A clinical test is needed that
      is reliable, valid, applicable to physical therapist practice, and appropriate
      for use in early and mid-stages of the disease. PROFILE PD is one such scale,
      consisting of 24 items that would typically be assessed during the physical
      therapist's examination and evaluation of individuals with PD. The purpose of
      this article is to report on clinimetric properties of the PROFILE PD and to make
      the test available for use. METHODS: Interrater reliability was determined using
      the intraclass correlation coefficient. Construct validity was determined by
      comparing scores on the PROFILE PD with the gold standard (Unified Parkinson's
      Disease Rating Scale [UPDRS]) as well as scales of physical activity and
      participation. Construct validity and structure of the PROFILE PD were further
      examined using exploratory factor analysis using principal component analysis
      with Promax rotation that allows a correlated factor structure. RESULTS:
      Interrater reliability of the PROFILE PD was high (ICC = 0.97). Construct
      validity was demonstrated with the UPDRS (r = 0.86, P < 0.0001), Schwab & England
      Activities of Daily Living Scale (S&E) (r = -0.83, P < 0.0001), and Continuous
      Scale Physical Functional Performance test (r = -0.62, P < 0.0001). Principal
      component analysis demonstrated that the test comprises a single scale.
      CONCLUSIONS: The PROFILE PD is a reliable and valid scale that can be used to
      quantify alterations in body systems and activity of individuals in early and mid
      stages of PD. Use of the scale can provide an overall summary of the impact of PD
      on body systems and activities.

PMID- 21084920
TI  - Functional and corticomotor changes in individuals with tetraplegia following
      unimanual or bimanual massed practice training with somatosensory stimulation: a
      pilot study.
AB  - BACKGROUND AND PURPOSE: In individuals with cervical spinal cord injury (SCI),
      damage to spinal pathways results in deficits of hand function; maladaptive
      cortical changes further impair function. Unimanual massed practice (MP) training
      with somatosensory stimulation (SS) has been shown to improve hand function and
      increase corticomotor excitability after SCI. However, bimanual training may be
      more beneficial as these individuals have bilateral impairment. We compared
      clinical and corticomotor changes associated with unimanual versus bimanual MP
      training, each combined with SS. METHODS: Participants were 13 individuals with
      chronic tetraplegia who had at least minimal voluntary control of the thenar
      muscles of 1 hand. The participants were randomly assigned to unimanual MP + SS
      or bimanual MP + SS. Clinical outcome measures included tests of unimanual
      (Jebsen Taylor Hand Function Test; JTT) and bimanual hand function (Chedoke Arm
      and Hand Activity Inventory; CAHAI), sensory function (monofilament test), and
      pinch grip strength. Neurophysiological outcome measures were corticomotor map
      area, center of gravity (COG), of the corticomotor map and corticomotor threshold
      as assessed by transcranial magnetic stimulation. RESULTS: There were no
      significant differences in outcomes between the unimanual MP + SS versus bimanual
      MP + SS groups, both groups showed significant improvements in the JTT, CAHAI,
      and monofilament test. However, trends suggest that the unimanual MP + SS group
      had greater improvement in the JTT whereas the bimanual MP + SS group had greater
      improvement on the CAHAI. Functional changes were accompanied by a strong trend
      toward increased corticomotor map area. DISCUSSION AND CONCLUSION: When combined
      with SS, both unimanual and bimanual MP training improve hand function and
      sensation in individuals with tetraplegia. Changes in hand function seem to be
      associated with increased corticomotor map area.

PMID- 21084921
TI  - Split-belt treadmill training poststroke: a case study.
AB  - BACKGROUND AND PURPOSE: Even after rehabilitation, many individuals with strokes
      have residual gait deviations and limitations in functional walking. Applying the
      principles of motor adaptation through a split-belt treadmill walking paradigm
      can lead to short-term improvements in step length asymmetry after stroke. The
      focus of this case study was to determine whether it is possible to capitalize on
      these improvements for long-term gain. CASE DESCRIPTION: The participant was a 36
      year-old woman who was 1.6 years poststroke. She had a slow walking speed and
      multiple specific gait deviations, including step length asymmetry. INTERVENTION:
      The participant walked on a split-belt treadmill 3 d/wk for 4 weeks, with the
      paretic leg on the slower of the two treadmill belts. The goal was 30 minutes of
      split-belt treadmill walking each day, followed by overground walking practice to
      reinforce improvements in step length symmetry. OUTCOMES: With training, step
      length asymmetry decreased from 21% to 9% and decreased further to 7% asymmetry 1
      month after training. Self-selected walking speed increased from 0.71 m/s to 0.81
      m/s after training and 0.86 m/s 1 month later. Percent recovery, measured by the
      Stroke Impact Scale (SIS), increased from 40% to 50% posttraining and to 60% 1
      month later. DISCUSSION: Improvements in step length symmetry were observed
      following training and these improvements were maintained 1 month later.
      Concomitant changes in clinical measures were also observed, although these
      improvements were modest. The outcomes for this participant are encouraging given
      the relatively small dose of training. They suggest that after stroke, short-term
      adaptation can be capitalized on through repetitive practice and can lead to
      longer-term improvements stroke.

PMID- 21084922
TI  - Transcutaneous electrical stimulation on acupoints combined with task-related
      training to improve motor function and walking performance in an individual 7
      years poststroke: a case study.
AB  - BACKGROUND AND PURPOSE: Impaired walking function and spasticity are common
      sequelae of stroke. Prior studies have shown that a rehabilitation program
      combining transcutaneous electrical stimulation (TES) with task-related training
      (TRT) improves motor function in individuals with stroke. However, it is unclear
      if this approach is beneficial for individuals with long-standing stroke. CASE
      DESCRIPTION: The subject of this case study was a 61-year-old man who was 7 years
      poststroke. He exhibited limitations of walking function, impaired strength of
      the ankle muscles, and severe plantarflexor spasticity. INTERVENTIONS: For 4
      weeks, the patient performed a 5-day/wk home program consisting of 60 minutes of
      TES (below motor threshold) to the acupoints in the affected lower leg, followed
      by 60 minutes of TRT. He documented his daily home program activities in a log,
      and 3 times a week he received a call from the therapist to verify his adherence.
      The patient also had 8 clinic visits, which focused on instruction to ensure
      adherence to the (TES + TRT) protocol and progression of the program. OUTCOMES:
      After the 4-week program, plantarflexor spasticity decreased and ankle dorsi- and
      plantarflexor strength improved. More important, there were notable improvements
      in gait velocity, walking endurance, and functional mobility. These gains were
      maintained at 4 weeks posttreatment. DISCUSSION: This accessible home program was
      safe and effective for decreasing impairment and improving function in an
      individual with long-term, chronic stroke. The gains were maintained 4 weeks
      posttreatment. Details are provided for developing a home program integrating
      somatosensory TES and TRT.

PMID- 21084923
TI  - Translating physical therapy interventions from bench to bedside: the value of
      case studies and published protocols.

PMID- 21084930
TI  - Physical activity in US youth: effect of race/ethnicity, age, gender, and weight
      status.
AB  - PURPOSE: To describe physical activity (PA) levels by race/ethnicity, age,
      gender, and weight status in a representative sample of US youth. METHODS: Cross
      sectional data from the 2003-2004 and 2005-2006 National Health and Nutrition
      Examination Survey were combined and analyzed. Youth aged 6-19 yr with at least
      four 10-h days of PA measured by accelerometry were included (n = 3106). Outcomes
      included mean counts per minute and minutes spent in moderate-to-vigorous PA
      (MVPA). RESULTS: Among the groups, the 6- to 11-yr-olds spent more time (88
      min.d) in MVPA than the 12- to 15-yr-olds (33 min.d) and 16- to 19-yr-olds (26
      min.d; P < 0.001 for both). Females spent fewer minutes per day in MVPA than
      males (P < 0.001). Overall, obese youth spent 16 fewer minutes per day in MVPA
      than normal-weight youth. However, non-Hispanic white males spent three to four
      fewer minutes per day in vigorous PA than Mexican American (MA; P = 0.004) and
      non-Hispanic black (P < 0.001) males but had lower obesity rates and obese 12- to
      15-yr-old MA recorded similar minutes in MVPA per day as normal-weight MA (P >
      0.050). There was a significant three-way age-body mass index-race/ethnicity
      interaction for mean minutes per day in MVPA (P < 0.001). Adjustment for total
      energy intake did not qualitatively alter these results. CONCLUSIONS: Females and
      older youth were the least active groups. Obese youth were generally less active,
      but this did not hold uniformly across race/ethnic groups. Cultural or biological
      factors could moderate the association between PA and obesity in youth.

PMID- 21084931
TI  - Exercise and type 2 diabetes: American College of Sports Medicine and the
      American Diabetes Association: joint position statement. Exercise and type 2
      diabetes.
AB  - Although physical activity (PA) is a key element in the prevention and management
      of type 2 diabetes mellitus (T2DM), many with this chronic disease do not become
      or remain regularly active. High-quality studies establishing the importance of
      exercise and fitness in diabetes were lacking until recently, but it is now well
      established that participation in regular PA improves blood glucose control and
      can prevent or delay T2DM, along with positively affecting lipids, blood
      pressure, cardiovascular events, mortality, and quality of life. Structured
      interventions combining PA and modest weight loss have been shown to lower T2DM
      risk by up to 58% in high-risk populations. Most benefits of PA on diabetes
      management are realized through acute and chronic improvements in insulin action,
      accomplished with both aerobic and resistance training. The benefits of physical
      training are discussed, along with recommendations for varying activities, PA
      associated blood glucose management, diabetes prevention, gestational diabetes,
      and safe and effective practices for PA with diabetes-related complications.

PMID- 21084932
TI  - New ground with new features. Comments from the editor.

PMID- 21084933
TI  - Pregnancy complications in women with uterine duplication abnormalities.
AB  - Patients with duplication anomalies have a higher incidence of infertility,
      repeated first trimester spontaneous abortions, fetal intrauterine growth
      restriction, fetal malposition, preterm labor, and retained placenta. The role of
      imaging is not only to detect and diagnose mullerian anomalies but also to help
      distinguish surgically correctable forms of mullerian duct anomalies from
      nonsurgical forms. Imaging is also important to identify the location of the
      pregnancy, because ultrasound guidance may be needed after miscarriage or when
      pregnancies occur in an ectopic location. Attention to the position of the fetus
      within a normal-appearing uterus, with normal thickness surrounding myometrium,
      is important for recognizing an otherwise unsuspected uterine duplication
      abnormality. In this article, we review and illustrate the imaging features and
      complications of uterine duplication anomalies in pregnancy and identify
      potential mimics of duplication anomalies.

PMID- 21084934
TI  - Sonography and computed tomography of the mimics of appendicitis.
AB  - There are numerous entities that can mimic acute appendicitis. Ultrasound and
      computed tomography are the most common first-line, cross-sectional imaging
      modalities in the acute care setting. Ideally, imaging will either confirm
      appendicitis or exclude it by identifying a normal appendix. In the latter
      scenario, an alternate diagnosis can frequently be established that range from
      genitourinary, gastrointestinal, to even abdominal wall processes. Imaging is
      especially helpful in cases of patients presenting with atypical signs/symptoms
      for acute appendicitis and those presenting with a classic presentation where an
      alternative diagnosis is determined. The correct diagnosis will allow the most
      appropriate clinical management and therapy; specifically, avoiding nonindicated
      surgery is essential. Common and uncommon mimics of acute appendicitis are
      discussed with specific attention to their sonographic and computed tomographic
      appearances.

PMID- 21084935
TI  - Acute pelvic pain: what we have learned from the ER.

PMID- 21084936
TI  - ACR appropriateness criteria(c) ovarian cancer screening.
AB  - The majority of women with ovarian cancer have advanced stage disease at the time
      of diagnosis and a poor 5 year survival rate. Hence, screening has been
      investigated in the hopes of improving survival by diagnosing ovarian cancer at
      an earlier stage. Most screening methods thus far have included ultrasound and/or
      serum tumor markers. However, low prevalence of the disease, high false positive
      rate of current screening methods, and the probable rapid growth of most ovarian
      carcinomas from no defined precursor lesion, all contribute to difficulty in
      screening for ovarian cancer. While screening may be able to detect ovarian
      cancer at an earlier stage, adequate data is presently lacking on whether
      screening improves survival. The results of ongoing large clinical trials will be
      available in a few years and should provide critical information regarding the
      usefulness of screening. Pending results of those large clinical trials,
      screening is not currently recommended for women at average risk for ovarian
      cancer. Screening is most likely to be performed in women with an increased
      familial risk of ovarian cancer, but patients should be aware that even with this
      risk factor, there is currently insufficient evidence to know if screening is
      effective. New screening methods, including new or multiple serum markers and
      proteomics, are also being investigated.

PMID- 21084937
TI  - How appropriate are the american college of radiology appropriateness criteria
      for ovarian cancer screening.

PMID- 21084958
TI  - Prenatal diagnosis of renal developmental anomalies associated with an empty
      renal fossa.
AB  - Fetal kidneys are evaluated on routine obstetric ultrasounds; therefore, fetal
      renal developmental anomalies are frequently encountered with prenatal screening.
      Absence of the fetal kidney from its expected location generates a differential
      diagnosis that originates from the knowledge of the developmental origins of the
      kidneys. Many of the renal developmental anomalies demonstrate overlapping
      features in both symptoms and imaging appearance. We illustrate the pertinent
      findings of selected fetal renal anomalies in the setting of a unilateral empty
      renal fossa and suggest an algorithm for differentiating between the diagnoses.
      Discussed anomalies include horseshoe kidney, pelvic kidney, crossed fused renal
      ectopia, and renal agenesis.

PMID- 21084959
TI  - Transvaginal ultrasonographic measurement of cervical length as a predictor of
      preterm birth: a systematic review with meta-analysis.
AB  - The advent of effective interventions to prevent preterm delivery such as 17
      hydroxyprogesterone and cerclage serve as an impetus to determine whether routine
      second trimester transvaginal cervical length screening can identify which women
      would benefit from these therapies. A systematic review was conducted, 957
      abstracts were screened, 234 articles underwent full-text review, and 23 studies
      were included in the final analysis including 26,792 women. Data from relevant
      studies were pooled to produce summary estimates of sensitivity, specificity, and
      likelihood ratios using a random effects model. The ideal criteria of
      transvaginal cervical length measurements to predict preterm delivery are
      discussed.

PMID- 21084960
TI  - Postmortem computed tomography in a case of Apert Syndrome: correlation with
      conventional autopsy and prenatal ultrasound.
AB  - BACKGROUND: There have been very few small studies or case reports in the
      literature considering noninvasive postmortem imaging as supplement to autopsy,
      especially in fetuses with skeletal dysplasias. Apert syndrome accounts for 4.5%
      of all patients with craniosynostotic syndromes. It is classically characterized
      by the triad of coronal craniosynostosis, midfacial hypoplasia, and symmetric
      bony syndactyly of the hands and feet. PURPOSE: Illustrate the accuracy of a
      postmortem computed tomography compared with a conventional autopsy as well as
      review common imaging findings in a case of prenatally diagnosed Apert syndrome.
      CASE: A 31-year-old woman was seen for a routine prenatal ultrasound. A
      craniofacial syndrome was suspected by prenatal ultrasound, and the anomalies
      raised the suspicion of Apert syndrome. After genetic counseling, it was chosen
      to terminate the pregnancy. A postmortem computed tomographic scan was performed,
      followed by a conventional autopsy that confirmed the findings. DISCUSSION:
      Computed tomography provides many advantages in postmortem assessment. Postmortem
      imaging cannot replace conventional autopsy but is superior in axial and
      appendicular skeleton assessment. These studies provide supplemental information
      that may guide the autopsy. In situations where the parents wish not to pursue an
      autopsy, postmortem imaging can provide useful clinical information.

PMID- 21084961
TI  - Carotid Doppler ultrasound findings in patients with left ventricular assist
      devices.
AB  - Left ventricular assist devices (LVADs) have been used to treat advanced heart
      failure refractory to medical management, as bridge therapy to myocardial
      recovery, as bridge therapy to cardiac transplantation, or as destination therapy
      for patients with unfavorable transplant candidacy. Neurologic complications are
      some of the most common and devastating complications in these patients.
      Preoperative carotid ultrasound is, therefore, a standard evaluation in patients
      at risk for cerebrovascular disease. Postoperative carotid artery Doppler
      sonography is performed in those patients with neurologic symptoms. It is likely,
      therefore, that sonographers, radiologists, and other physicians working in a
      center where LVADs are implanted will likely encounter a carotid artery Doppler
      study in this patient group. To our knowledge, the carotid Doppler findings in
      these patients have never been published. We review the Doppler ultrasound
      findings in 6 patients after LVAD insertion.

PMID- 21084963
TI  - Diverse phenotypic profile of uterine tumors resembling ovarian sex cord tumors:
      an immunohistochemical study of 12 cases.
AB  - BACKGROUND: Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare
      neoplasms thought to be of putative endometrial stromal origin and solely
      composed of sex cord elements. Our study aimed to delineate the immunophenotype
      of these tumors and to verify whether their morphology reflects true sex cord
      like differentiation. DESIGN: Representative paraffin blocks from 12 UTROSCTs
      were selected after confirmation of the diagnosis. Cords and/or trabeculae were
      seen in all tumors, whereas tubules, diffuse areas, and a retiform pattern were
      present in 9, 6, and 2 cases, respectively. Tumors were stained for sex cord
      (inhibin, calretinin, WT1, and melan-A), epithelial (KL1 and epithelial membrane
      antigen), and smooth muscle markers (smooth muscle actin, desmin, smooth muscle
      myosin heavy chain, h-caldesmon, and histone deacetylase-8), CD10, HMB45, S100,
      and CD117. Intensity and percentage of staining were recorded. RESULTS: Six out
      of 12 tumors were positive for sex cord markers (inhibin 3 of 12, calretinin 4 of
      12, WT1 4 of 12, and melan-A 3 of 11) with 4 tumors coexpressing more than one
      marker. Half of the UTROSCTs showed positivity for KL1, with 2 tumors
      coexpressing epithelial membrane antigen. All but one tumor expressed one or more
      smooth muscle markers, with smooth muscle actin, desmin and histone deacetylase-8
      being most commonly expressed. CD10 was positive in 6 of 12 tumors, CD117 in 4 of
      12, and S100 in 2 of 11 tumors, whereas HMB45 was negative in 11 tumors tested.
      CONCLUSIONS: UTROSCTs have a diverse immunohistochemical profile often
      coexpressing sex cord, epithelial, and smooth muscle markers. The expression of
      smooth muscle markers in these tumors does not imply a smooth muscle origin as
      endometrial and sex cord stromal tumors are not infrequently positive for these
      markers. Positivity for sex cord markers supports a true sex cord/steroid
      phenotype. Although the immunohistochemical profile of these tumors overlaps with
      that of endometrial stromal tumors with sex cord-like differentiation as well as
      ovarian sex cord stromal tumors, the origin of UTROSCT remains uncertain.

PMID- 21084962
TI  - Intra-ampullary papillary-tubular neoplasm (IAPN): characterization of tumoral
      intraepithelial neoplasia occurring within the ampulla: a clinicopathologic
      analysis of 82 cases.
AB  - BACKGROUND: There has been no uniform terminology for systematic analysis of mass
      forming preinvasive neoplasms (which we term tumoral intraepithelial neoplasia)
      that occur specifically within the ampulla. Here, we provide a detailed analysis
      of these neoplasms, which we propose to refer to as intra-ampullary papillary
      tubular neoplasm (IAPN). MATERIALS AND METHODS: Three hundred and seventeen
      glandular neoplasms involving the ampulla were identified through a review of
      1469 pancreatoduodenectomies and 11 ampullectomies. Eighty-two neoplasms
      characterized by substantial preinvasive exophytic component that grew almost
      exclusively (>75%) within the ampulla (in the ampullary channel or intra
      ampullary portions of the very distal segments of the common bile duct or
      pancreatic duct) were analyzed. RESULTS: (1) Clinical: The mean age was 64 years,
      male/female ratio was 2.4, and mean tumor size was 2.7 cm. (2) Pathology: The
      tumors had a mixture of both papillary and tubular growth (each constituting at
      least 25% of the lesion) in 57%; predominantly (>75%) papillary in 23%, and
      predominantly (>75%) tubular in 20%. High-grade dysplasia was present in 94% of
      cases, of which 39% showed focal (<25% of the lesion), 28% showed substantial
      (25% to 75%), and 27% showed extensive (>75%) high-grade dysplasia. In terms of
      cell-lineage morphology, 45% had a mixture of patterns. However, when evaluated
      with a forced-binary approach as intestinal (INT) versus gastric/pancreatobiliary
      (GPB) based on the predominant pattern, 74% were classified as INT and 26% as
      GPB. (3) Immunohistochemistry: Percent sensitivity/specificity of cell-lineage
      markers were, for INT phenotype: MUC2 85/78 and CDX2 94/61; and for GBP: MUC1
      89/79, MUC5AC 95/69, and MUC6 83/76, respectively. Cytokeratin 7 and 20 were
      coexpressed in more than half. (4) Invasive carcinoma: In 64 cases (78%), there
      was an associated invasive carcinoma. Size of the tumor and amount of dysplasia
      correlated with the incidence of invasion. Invasive carcinoma was of INT-type in
      58% and of pancreatobiliary-type in 42%. Cell lineage in the invasive component
      was the same as that of the preinvasive component in 84%. All discrepant cases
      were pancreatobiliary-type invasions, which occurred in INT-type preinvasive
      lesions. (5) OUTCOME: The overall survival of invasive cases were significantly
      worse than that of noninvasive ones (57% vs. 93%; P=0.01); and 3 years, 69%
      versus 100% (P=0.08); and 5 years, 45% versus 100% (P=0.07), respectively. When
      compared with 166 conventional invasive carcinomas of the ampullary region,
      invasive IAPNs had significantly better prognosis with a mean survival of 51
      versus 31 months (P<0.001) and the 3-year survival of 69% versus 44% (P<0.01).
      CONCLUSIONS: Tumoral intraepithelial neoplasia occurring within the ampulla are
      highly analogous to pancreatic or biliary intraductal papillary and tubular
      neoplasms as evidenced by their papillary and/or tubular growth, variable cell
      lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence), and thus
      we propose to refer to these as IAPN. IAPNs are biologically indolent;
      noninvasive examples show an excellent prognosis, whereas those with invasion
      exhibit a malignant but nevertheless significantly better prognosis than typical
      invasive ampullary carcinomas unaccompanied by IAPNs. Twenty eight percent (64 of
      230) of invasive carcinomas within the ampulla arise in association with IAPNs.

PMID- 21084964
TI  - Intracystic papillary carcinoma of the breast: An in situ or invasive tumor?
      Results of immunohistochemical analysis and clinical follow-up.
AB  - Intracystic papillary carcinoma (IPC) is regarded as an intraductal neoplasm, but
      recent evidence suggests that it could be invasive, as it often lacks
      myoepithelial lining. We evaluated myoepithelial cells and collagen IV, a
      basement membrane component, in 40 IPCs from 39 (35 female and 4 male) patients
      and assessed their clinical management and follow-up. The mean patient age at
      diagnosis was 68 years, and the mean tumor size was 1.8 cm. Thirteen cases were
      pure IPC, 8 cases were IPC with or without microinvasion, and 19 cases were IPC
      with invasive carcinoma (IPC+IC), including 1 mucinous and 1 cribriform
      carcinoma. Ductal carcinoma in situ associated more often with IPC+IC (84.2%)
      than with pure IPC (61.5%) or IPC with or without microinvasion (62.5%).
      Myoepithelial cells were completely absent in 33 of 40 (82.5%) IPCs, and only
      focal in the remaining 7 of 40 cases (17.5%). Collagen IV lining was
      discontinuous in most cases (89%). All tumors were estrogen receptor positive and
      HER2 negative; most were progesterone receptor positive (93%). Eleven patients
      underwent mastectomy and 28 lumpectomy; 3 of 27 (11%) patients had lymph node
      involvement. Fourteen of all patients treated with breast conservation received
      radiation, 10 hormonal treatment, and none chemotherapy. Four patients treated
      conservatively (3 with pure IPC and 1 with IPC+IC) recurred locally, including
      one who later developed bone metastasis. We conclude that IPC constitutes a
      spectrum of intraductal and IC, with predominance of the latter. IPC rarely
      involves lymph nodes and carries very good prognosis, but can recur locally. This
      type of tumor is strongly estrogen receptor positive and hormonal therapy should
      be pursued for its management, whereas the benefit of radiation after lumpectomy
      remains unclear.

PMID- 21084965
TI  - FLI-1 distinguishes Ewing sarcoma from small cell osteosarcoma and mesenchymal
      chondrosarcoma.
AB  - Small cell osteosarcoma and mesenchymal chondrosarcoma are 2 primary bone tumors
      with a small round blue cell component, which can mimic the appearance of Ewing
      sarcoma. Distinguishing these tumors from each other on biopsy material is
      important clinically, as optimal therapy differs according to the tumor type.
      However, separating these entities on morphology alone can be challenging. FLI-1
      has been described to be a useful marker for Ewing sarcoma, particularly when
      hematolymphoid markers are negative. In small cell osteosarcoma and mesenchymal
      chondrosarcoma, the FLI-1 staining pattern has not been adequately characterized.
      Using a monoclonal FLI-1 antibody, nuclear immunoreactivity in tumor cells was
      evaluated in 10 small cell osteosarcomas, 10 mesenchymal chondrosarcomas, and 8
      Ewing sarcomas, together with a number of other small, round, blue cell tumors.
      None of the small cell osteosarcomas or mesenchymal chondrosarcomas exhibited FLI
      1 staining in the tumor cells, in contrast to the positive nuclear FLI-1 staining
      in the stromal endothelial cells. In comparison, 6 of the 8 Ewing sarcomas showed
      moderate-to-strong nuclear FLI-1 staining of the tumor cells in addition to
      strong staining of the stromal endothelial cell nuclei. With the exception of
      lymphoblastic lymphomas, FLI-1 positivity was not seen in the other small round
      blue cell tumors examined. These findings show that, in contrast to Ewing
      sarcoma, small cell osteosarcoma and mesenchymal chondrosarcoma lack FLI-1
      immunoreactivity. FLI-1 is therefore useful in the differential diagnosis of
      small round blue cell tumors of the bone.

PMID- 21084967
TI  - Simple implantation of a temporary right ventricular device for right ventricular
      failure after left ventricular device implantation via a left lateral
      thoracotomy.
AB  - Right ventricular (RV) support in the case of RV failure after left ventricular
      assist device (LVAD) implantation is a well-established surgical therapeutic
      option. However, there is a serious limitation of RV support after the insertion
      of a LVAD through lateral thoracotomy in patients who have undergone previous
      multiple cardiac operations. We describe a modified surgical approach for
      implantation of right ventricular assist devices (RVADs) via left lateral
      thoracotomy, with venous cannulation via a femoral vein and transpericardial
      outflow cannulation of the main pulmonary artery by Seldinger technique under
      echocardiographic monitoring. This technique was successfully used in a case with
      subsequent weaning from the RVAD after 10 days of support.

PMID- 21084966
TI  - Predilution versus postdilution continuous venovenous hemofiltration: no effect
      on filter life and azotemic control in critically ill patients on heparin.
AB  - In continuous venovenous hemofiltration (CVVH), the delivery of replacement fluid
      in pre- or postdilution mode remains the subject of controversy. We compared both
      modes in terms of filter life, dose, and azotemic control. All patients admitted
      to the intensive care units of a university hospital between November 2004 and
      December 2006 receiving CVVH and systemic anticoagulation with heparin were
      retrospectively studied. Thirty-six patients treated by CVVH in predilution and
      27 in postdilution mode were studied, with 132 filters in the former and 111 in
      the latter. The filter life [median +/- interquartile range (IQR)] was 24 +/- 38
      hours and 29 +/- 46 hours (p = 0.58) in the pre- and postdilution modes,
      respectively. Although the fall in creatinine and urea depended on the dose, 19%
      greater delivered dose in the post- than predilution mode did not impact on
      azotemic control. In critically ill, heparinized patients on CVVH, filter life
      and azotemic control are similar in pre- and postdilution modes and underscore
      the clinical applicability of the predilution mode.

PMID- 21084969
TI  - Masked hypertension in untreated normotensives: difference between a work day and
      a leisure day?
AB  - OBJECTIVE: To compare ambulatory blood pressure recorded during a work day with a
      leisure day regarding masked hypertension. DESIGN: A randomized crossover study
      in middle-aged normotensives. PARTICIPANTS: Thirty-seven untreated middle-aged
      normotensives (17 women), who had repeated office blood pressure less than 140/90
      mmHg. MAIN OUTCOME MEASURE: Individual difference of masked hypertension between
      a work day and a leisure day. RESULTS: Office systolic/diastolic blood pressure
      mean (SD) was 0.3/0.6 (6.4/5.2) mmHg higher during the work day. The mean (SD)
      systolic/diastolic 24-h, day and night blood pressure was 2.8/3.1 (4.5/3.6),
      2.2/2.5 (4.9/4.2) and 1.3/1.9 (4.6/4.0) mmHg higher during the work day than
      during the leisure day. Individual comparisons of occurrence of ambulatory blood
      pressure values above normal during day (systolic >=135 or diastolic >=85) showed
      a statistically significant difference between the work day and the leisure day,
      P=0.0412. The P values for the individual comparisons of occurrence of ambulatory
      blood pressure values above normal during 24 h (systolic >=130 or diastolic
      >=80), and during night (systolic >=120 or diastolic >=70 mmHg) were P=0.0771 and
      0.6171, respectively. CONCLUSION: Ambulatory blood pressure was somewhat higher
      during the work day than during the leisure day, and there was statistically
      significant individual difference concerning masked hypertension during daytime.
      Thus, in normotensives such as in hypertensives, ambulatory blood pressure during
      a work day seems to give the best information. Diastolic blood pressure values
      above normal were more common than systolic. However, systolic blood pressure is
      considered of greater importance in this age group and no participant had
      extremely high values.

PMID- 21084968
TI  - Total liquid ventilation provides superior respiratory support to conventional
      mechanical ventilation in a large animal model of severe respiratory failure.
AB  - Total liquid ventilation (TLV) has the potential to provide respiratory support
      superior to conventional mechanical ventilation (CMV) in the acute respiratory
      distress syndrome (ARDS). However, laboratory studies are limited to trials in
      small animals for no longer than 4 hours. The objective of this study was to
      compare TLV and CMV in a large animal model of ARDS for 24 hours. Ten sheep
      weighing 53 +/- 4 (SD) kg were anesthetized and ventilated with 100% oxygen.
      Oleic acid was injected into the pulmonary circulation until PaO2:FiO2 <= 60 mm
      Hg, followed by transition to a protective CMV protocol (n = 5) or TLV (n = 5)
      for 24 hours. Pathophysiology was recorded, and the lungs were harvested for
      histological analysis. Animals treated with CMV became progressively hypoxic and
      hypercarbic despite maximum ventilatory support. Sheep treated with TLV
      maintained normal blood gases with statistically greater PO2 (p < 10(-9)) and
      lower PCO2 (p < 10(-3)) than the CMV group. Survival at 24 hours in the TLV and
      CMV groups were 100% and 40%, respectively (p < 0.05). Thus, TLV provided gas
      exchange superior to CMV in this laboratory model of severe ARDS.

PMID- 21084970
TI  - A psychophysiologic reaction to application of ambulatory blood pressure monitor:
      fact or artifact?
AB  - BACKGROUND: The study investigated the clinical significance of relatively high
      blood pressure (BP) elevations during the calibration of the ambulatory blood
      pressure monitor (ABPM). METHODS: Inferences were drawn from the analysis of
      differences between 'M', the average of five manually triggered responses, and
      'W', the average daytime BP. M-W differences were calculated from ABPM recordings
      of consecutive patients (N=276), grouped diagnostically, on the basis of ABPM
      results, into normotensive (71), untreated hypertensive (77), and treated
      hypertensive (128). RESULTS: All three diagnostic groupings showed a highly
      significant preponderance of the number of positive M-W differences over negative
      ones for systolic blood pressure and diastolic blood pressure but not heart rate.
      When the criteria of substantial M-W differences were arbitrarily set to 20 mmHg
      or more for systolic blood pressure and 10 mmHg or more for diastolic blood
      pressure, a highly significant preponderance was also found for substantial
      positive M-W differences over negative ones. For each of the two results above
      there was no significant difference among groups: normotensive, untreated
      hypertensive, and treated hypertensive. BP values coinciding with the removal of
      the monitor were also significantly higher than average waking values, but the
      magnitude of the difference was smaller than that between the values at
      application. CONCLUSIONS: Results support the interpretation that the initial BP
      spikes with a substantial M-W difference represent psychophysiologic reactions
      triggered by the perceived stresses of the application of the ABPM. Substantial
      calibration spikes that connect to substantial 'first hour elevations' may be the
      start of a white coat response. The inclusion of valid calibration data in the
      analysis of the ABPM result is recommended.

PMID- 21084971
TI  - Nurses' perceptions and experiences with the implementation of a medication
      administration system.
AB  - The purpose of this article was to describe facilitators and barriers to the
      implementation of a commercially available electronic medication administration
      record system at two pediatric hospitals. Qualitative interviews were conducted
      at 6 and 18 months after implementation with a convenience sample of nurses
      working on either the medical-surgical or ICUs. The 18-month interview reassessed
      barriers identified to the adoption of the electronic medication administration
      record system at the 6-month interview. The vast majority of respondents (85%)
      indicated that the implementation plan met their expectations. The most
      significant barrier to adoption (identified by 72% of respondents) was excessive
      time for logging into the system. After 18 months, respondent satisfaction
      increased considerably as modifications to the electronic medication
      administration record system were made, and adjustments to workflow resulted in
      streamlined nurse work processes coupled with increased productivity and enhanced
      patient safety. While this study confirms that nursing staff acceptance of health
      information technology is aided by the system's ability to improve patient safety
      and accessibility of patient information, we also found that factors unrelated to
      the actual software or the system could be important determinants of users'
      satisfaction.

PMID- 21084972
TI  - Costing nursing care: using the clinical care classification system to value
      nursing intervention in an acute-care setting.
AB  - The purpose of this study was to combine an established methodology for coding
      nursing interventions and action types using the Clinical Care Classification
      System with a reliable formula (relative value units) to cost nursing services.
      Using a flat per-diem rate to cost nursing care greatly understates the actual
      costs and fails to address the high levels of variability within and across
      units. We observed nurses performing commonly executed nursing interventions and
      recorded these into an electronic database with corresponding Clinical Care
      Classification System codes. The duration of these observations was used to
      calculate intervention costs using relative value unit calculation formulas. The
      costs of the five most commonly executed interventions were nursing care
      coordination/manage-refer ($2.43), nursing status report/assess-monitor ($4.22),
      medication treatment/perform-direct ($6.33), physical examination/assess-monitor
      ($3.20), and universal precautions/perform-direct ($1.96). Future studies across
      a variety of nursing specialties and units are needed to validate the relative
      value unit for Clinical Care Classification System action types developed for use
      with the Clinical Care Classification System nursing interventions as a method to
      cost nursing care.

PMID- 21084973
TI  - Using m-learning on nursing courses to improve learning.
AB  - Modern handheld devices and wireless communications foster new kinds of
      communication and interaction that can define new approaches to teaching and
      learning. Mobile learning (m-learning) seeks to use them extensively, exactly in
      the same way in which e-learning uses personal computers and wired communication
      technologies. In this new mobile environment, new applications and educational
      models need to be created and tested to confirm (or reject) their validity and
      usefulness. In this article, we present a mobile tool aimed at self-assessment,
      which allows students to test their knowledge at any place and at any time. The
      degree to which the students' achievement improved is also evaluated, and a
      survey on the students' opinion of the new tool was also conducted. An
      experimental group of 20- to 21-year-old nursing students was chosen to test the
      tool. Results show that this kind of tool improves students' achievement and does
      not make necessary to introduce substantial changes in current teaching
      activities and methodology.

PMID- 21084974
TI  - Challenges of using the internet for behavioral research.
AB  - Using the Internet in behavioral research remains a challenge. We developed a
      video intervention and conducted a pilot study that was designed to deliver and
      test the intervention via the Internet. One aim of this study was to evaluate the
      feasibility of using the Internet to both deliver the intervention and collect
      data from participants. This article summarizes procedures for delivering the
      intervention and survey via the Internet, obstacles encountered during delivery
      of the intervention and data collection, and lessons learned that can be applied
      to future research involving the Internet.

PMID- 21084975
TI  - Graphical arterial blood gas visualization tool supports rapid and accurate data
      interpretation.
AB  - A visualization tool that integrates numeric information from an arterial blood
      gas report with novel graphics was designed for the purpose of promoting rapid
      and accurate interpretation of acid-base data. A study compared data
      interpretation performance when arterial blood gas results were presented in a
      traditional numerical list versus the graphical visualization tool. Critical-care
      nurses (n = 15) and nursing students (n = 15) were significantly more accurate
      identifying acid-base states and assessing trends in acid-base data when using
      the graphical visualization tool. Critical-care nurses and nursing students using
      traditional numerical data had an average accuracy of 69% and 74%, respectively.
      Using the visualization tool, average accuracy improved to 83% for critical-care
      nurses and 93% for nursing students. Analysis of response times demonstrated that
      the visualization tool might help nurses overcome the "speed/accuracy trade-off"
      during high-stress situations when rapid decisions must be rendered. Perceived
      mental workload was significantly reduced for nursing students when they used the
      graphical visualization tool. In this study, the effects of implementing the
      graphical visualization were greater for nursing students than for critical-care
      nurses, which may indicate that the experienced nurses needed more training and
      use of the new technology prior to testing to show similar gains. Results of the
      objective and subjective evaluations support the integration of this graphical
      visualization tool into clinical environments that require accurate and timely
      interpretation of arterial blood gas data.

PMID- 21084976
TI  - Podcasting as an instructional supplement to online learning: a pilot study.
AB  - There is increasing interest in the use of mobile technologies for nursing
      educational purposes in academic settings, but few evaluative studies exist.
      Understanding the best use of podcasting during distance learning is basic for
      instructional design. This pilot study compared online reading to a supplementary
      podcast to determine graduate nursing students' preferences and usage. Results
      indicated that students did not download the podcast to a mobile device but
      multitasked while listening. The podcast and the readings were equally supported
      as important by nursing students. Podcasting in distance-accessible courses may
      engage students by providing a human voice and thus a better virtual connection.
      Podcasting is only one method of knowledge acquisition; distance learning courses
      should consider providing multiple learner-centered delivery methods, given the
      variety of learning styles.

PMID- 21084977
TI  - Multimedia computerized smoking awareness education for low-literacy Hispanics.
AB  - To meet the needs of low-literacy, underserved, Mexican-American patients, this
      transdisciplinary team created a freestanding computer kiosk. Smoking awareness
      and cessation were the topic chosen. Focus groups were used to inform the design
      and creation of each screen to include appropriate culturally based images and
      messages. A kiosk was placed in a primary care clinic in a West Texas city. User
      feedback was collected, showing that this method of patient education is
      acceptable.

PMID- 21084978
TI  - Persistent falcine sinus and unilateral renal agenesis in a girl with Sotos
      syndrome.
AB  - Sotos syndrome is an overgrowth syndrome characterized by distinctive facial
      features, developmental delay, and macrocephaly. Here, we present a 10-year-old
      girl with prenatal and postnatal overgrowth, prominent forehead, pointed chin,
      and advanced bone age. She also has a persistent falcine sinus in the posterior
      falx cerebri, patent ductus arteriosus, unilateral renal agenesis, and scoliosis.
      A pituitary macroadenoma was also found with external compression of the inferior
      aspect of the optic chiasm. We identified a de novo missense mutation of the NSD1
      (nuclear receptor-binding SET domain protein 1) gene in this patient.
      Computational three-dimensional structural analysis revealed that the NSD1
      mutation induced major alterations.

PMID- 21084979
TI  - Cutaneous features in 17q21.31 deletion syndrome: a differential diagnosis for
      cardio-facio-cutaneous syndrome.
AB  - Microdeletion of 17q21.31 causes a recurrent recognizable dysmorphic syndrome. A
      further four patients with 17q21.31 microdeletions are reported here in whom an
      earlier diagnosis of cardio-facio-cutaneous syndrome was suggested. These
      patients have significant similarities of facial gestalt to earlier reported
      17q21.31 microdeletion patients, but a striking feature that has not been
      emphasized previously is the large number of naevi and other pigmentary skin
      abnormalities that may be present. These features, together with a coarse facial
      appearance, relative macrocephaly and significant learning disabilities, were
      what had led to the earlier diagnostic suggestion of cardio-facio-cutaneous
      syndrome in each of these four cases.

PMID- 21084980
TI  - Cardiac preload: hemodynamic physiology during thoracic surgery.
AB  - PURPOSE OF REVIEW: Operations in pleural cavity have circulatory effects both in
      pulmonary and systemic circulations. Nevertheless studies of these effects have
      yielded conflicting results. The importance of good understanding of hemodynamic
      changes during the operation in pleural cavity consists in fact that they are one
      of the factors influencing postoperative course of operated patients. RECENT
      FINDINGS: Dominating changes in the hemodynamics are represented by an increase
      of the cardiac output after opening the pleura. Changes in the arterial pressure
      are clinically unimportant and decreased cardiac output cannot be explained by
      preload as the preload is almost constant during the whole operation procedure.
      Arterial pressures in the pulmonary circulation are also increased after opening
      of pleura but only in the hip position so it depends on the body position rather
      than on the operation itself. SUMMARY: As far as it is known, circulatory and
      ventilatory consequences of thoracotomy are influenced particularly by the
      position of the patient's body on the operation table. During operation performed
      on the lung hemodynamics are influenced particularly by the individual steps of
      the operation procedure and by the position of the body. The hemodynamics are
      also influenced by metabolic functions of lungs particularly by the increased
      turnover of catecholamines in the lungs (increased total peripheral resistance
      and arterial pressures).

PMID- 21084981
TI  - Anesthetic management for lung transplantation.
AB  - PURPOSE OF REVIEW: For end-stage lung disease refractory to medical management,
      lung transplantation remains the definitive treatment. However, this procedure
      presents unique challenges for the anesthesiologist. This review summarizes the
      recent literature regarding this procedure and its anesthetic management. RECENT
      FINDINGS: Changes in the lung allocation system have had an impact on the
      characteristics of patients presenting for lung transplantation, resulting in
      patients who are older, sicker, and possibly presenting for retransplantation. In
      addition, various donor and recipient characteristics, including BMI, race, sex,
      and comorbidities such as diabetes and atrial fibrillation, have been shown to
      influence outcomes. Perioperative management, particularly colloid
      administration, adequate pain control, and treatment of pulmonary hypertension,
      may also affect outcomes. SUMMARY: Careful preoperative assessment of pulmonary
      and cardiac function and comorbidities are particularly important for this
      patient population. Lung protective strategies, intra-operative transesophageal
      echocardiogram, pulmonary artery catheterization, cardiopulmonary bypass, inhaled
      nitric oxide, and inhaled prostacyclin are all important tools for the
      anesthesiologist to optimize patient care.

PMID- 21084982
TI  - One-lung ventilation and arterial oxygenation.
AB  - PURPOSE OF REVIEW: Hypoxemia during one-lung ventilation (OLV) has become less
      common; however, it may still occur in about 10% of cases. We review recent
      developments which may affect the incidence and treatment of hypoxemia during
      OLV. RECENT FINDINGS: Changes in surgical techniques are affecting oxygenation
      during OLV. The increased use of the supine position may adversely affect the
      prevalence of hypoxemia, whereas the increased application of thoracoscopic
      techniques is limiting the treatment options. Treatment options such as global or
      selective recruitment maneuvers and drug effects of dexmedetomidine and
      epoprostenol on arterial oxygenation during OLV are discussed. Capnometry prior
      to, or early during OLV, may in fact be able to predict the degree of hypoxemia
      during OLV. Persistent controversies surrounding the effect of epidural
      anesthesia, ventilatory modalities and gravity are reviewed. SUMMARY: Interesting
      concepts have emerged from case reports and small studies on the treatment and
      prediction of hypoxemia during OLV. Definitive studies on the most effective
      ventilatory mode remain elusive. End-organ effects of OLV are an exciting new
      concept that may shape clinical practice and research going forward.

PMID- 21084983
TI  - Prevention of atrial fibrillation after cardiac surgery.
AB  - PURPOSE OF REVIEW: Atrial fibrillation after cardiac surgery remains a very
      common and vexing clinical problem. This review summarizes recent clinical and
      laboratory investigations, the results of which may lead to a more effective
      strategy for the prevention of atrial fibrillation after cardiac surgery. RECENT
      FINDINGS: The incidence of atrial fibrillation after cardiac surgery remains high
      (60% in some series), and there is no single strategy that reliably prevents it.
      Age, prior history, valvular surgery, and left atrial pathology and dysfunction
      are associated with the development of postoperative atrial fibrillation.
      Mortality in patients who develop new-onset atrial fibrillation after cardiac
      surgery is increased. Drug treatment with beta-blockers, amiodarone, statins,
      steroids, magnesium, and sotalol can be effective in preventing postoperative
      atrial fibrillation. Current guidelines for the prevention of postoperative
      atrial fibrillation are underutilized, which offers an opportunity for
      improvement. A new drug, vernakalant, has proved effective and well tolerated for
      chemical conversion of atrial fibrillation after cardiac surgery to sinus rhythm.
      SUMMARY: Atrial fibrillation after cardiac surgery remains a dysrhythmia with
      significant implications. A more comprehensive, multimodal preventive strategy,
      using preoperative beta-blockers and statins, perioperative magnesium and
      steroids, and preoperative amiodarone in high-risk patients should be rigorously
      evaluated.

PMID- 21084984
TI  - Perioperative pain management after thoracotomy.
AB  - PURPOSE OF REVIEW: Perioperative acute pain and the development of persistent
      pain after thoracotomy are major problems severely affecting health-related
      quality of life. This review examines and highlights recent strategies and
      advances in perioperative pain management in this field. RECENT FINDINGS: Despite
      the fact that thoracic epidural analgesia (TEA) is considered the 'gold standard'
      of perioperative care after thoracotomy, other local and regional techniques have
      emerged within recent years and seem to become valid alternatives to TEA. The use
      of continuous paravertebral blockade, in particular, may provide similar
      analgesia and fewer adverse effects than TEA. Multimodal systemic approaches,
      including the use of ketamine and gabapentinoids are being investigated as well
      as the effect of surgical techniques and adjuvant therapies such as
      transcutaneous electrical nerve stimulation on post-thoracotomy pain. SUMMARY:
      Even though thoracotomy is associated with significant postoperative
      complications, a growing understanding of the underlying pathophysiology and
      advances in multimodal pain therapy concepts in this specific group of patients
      are promising improved postoperative outcomes and potential reduction of the
      incidence of persistent pain.

PMID- 21084985
TI  - Surgical approach to end-stage heart failure.
AB  - PURPOSE OF REVIEW: End-stage heart failure is a challenging disease with growing
      incidence. With decreasing heart transplant rates worldwide organ preserving
      therapies become, again, of interest. The purpose of the present review is to
      examine the potential challenges of surgical therapies in patients with end-stage
      heart failure. RECENT FINDINGS: The gold-standard for end-stage heart failure is
      and will be cardiac transplantation. However, due to organ shortage this therapy
      is limited to a few patients. Therefore implantation of ventricular assist
      devices (VADs) or long-term minimal-invasive partial support devices will
      increase. Improvements in device design with smaller devices, easier implantation
      techniques, and modified anticoagulation outcome and long-term success will
      likely improve. In addition, good quality of life as destination therapy is
      almost available. Organ conservation surgery (coronary artery bypass grafting and
      surgical ventricular restoration or surgical repair of mitral valve
      regurgitation) in end-stage heart failure patients could not prove the expected
      results. Transcatheter or minimal-invasive approaches of these therapies might
      become routine in the near future. SUMMARY: Due to the overwhelming outcome
      rates, cardiac transplantation is the most established surgical therapy for end
      stage heart failure. VAD therapy is increasing and minimized VADs might further
      open the market for destination therapy/permanent support.

PMID- 21084986
TI  - Five-year incidence and progression of hearing impairment in an older population.
AB  - OBJECTIVES: There are few epidemiological surveys that have examined age-related
      hearing loss in an older Australian population. This study reports the
      prevalence, 5-yr incidence, and progression of hearing impairment in a
      representative sample of older persons. DESIGN: The Blue Mountains Hearing Study
      (BMHS) is a population-based survey of age-related hearing loss conducted among
      participants of the Blue Mountains Eye Study cohort. During the period 1997-1999,
      2956 had audiometric testing done. Of these, 870 participants without hearing
      loss and 439 with hearing loss were re-examined from 2002 to 2004. RESULTS: Some
      degree of hearing loss was present in 33.0% of this population at baseline.
      Prevalence of hearing loss increased with age, sex-adjusted (odds ratio [OR] 3.5,
      95% confidence interval [CI] 3.1-3.9), with men 70% more likely than women to
      have hearing loss. The 5-yr incidence of hearing impairment was 17.9%. For each
      decade of age older than 60 yrs, the risk of hearing loss increased threefold, OR
      3.9 (CI 2.3-3.8). Gender was not associated with incident hearing loss OR.
      However, high occupational prestige was associated with decreased incidence of
      hearing loss OR 0.6 (CI 0.40-0.94). The 5-yr progression of hearing loss defined
      as a difference in pure-tone average that exceeded 10 dB was relatively high
      (15.7%). At the baseline hearing study and at the 5-yr follow-up hearing study,
      57.4% and 59.7% of hearing impaired subjects, respectively, reported using a
      hearing aid for a maximum of 5 yrs. CONCLUSIONS: Hearing loss was a frequent
      sensory disability, with one in three persons having a hearing impairment, and of
      these, almost one in two showing a decline in hearing over a 5-yr period. This
      information can potentially contribute to the planning and resource investment in
      auditory rehabilitation services for older Australians.

PMID- 21084987
TI  - Within-subjects comparison of the HiRes and Fidelity120 speech processing
      strategies: speech perception and its relation to place-pitch sensitivity.
AB  - OBJECTIVES: Previous studies have confirmed that current steering can increase
      the number of discriminable pitches available to many cochlear implant (CI)
      users; however, the ability to perceive additional pitches has not been linked to
      improved speech perception. The primary goals of this study were to determine (1)
      whether adult CI users can achieve higher levels of spectral cue transmission
      with a speech processing strategy that implements current steering (Fidelity120)
      than with a predecessor strategy (HiRes) and, if so, (2) whether the magnitude of
      improvement can be predicted from individual differences in place-pitch
      sensitivity. A secondary goal was to determine whether Fidelity120 supports
      higher levels of speech recognition in noise than HiRes. DESIGN: A within
      subjects repeated measures design evaluated speech perception performance with
      Fidelity120 relative to HiRes in 10 adult CI users. Subjects used the novel
      strategy (either HiRes or Fidelity120) for 8 wks during the main study; a subset
      of five subjects used Fidelity120 for three additional months after the main
      study. Speech perception was assessed for the spectral cues related to vowel F1
      frequency, vowel F2 frequency, and consonant place of articulation; overall
      transmitted information for vowels and consonants; and sentence recognition in
      noise. Place-pitch sensitivity was measured for electrode pairs in the apical,
      middle, and basal regions of the implanted array using a psychophysical pitch
      ranking task. RESULTS: With one exception, there was no effect of strategy (HiRes
      versus Fidelity120) on the speech measures tested, either during the main study
      (N = 10) or after extended use of Fidelity120 (N = 5). The exception was a small
      but significant advantage for HiRes over Fidelity120 for consonant perception
      during the main study. Examination of individual subjects' data revealed that 3
      of 10 subjects demonstrated improved perception of one or more spectral cues with
      Fidelity120 relative to HiRes after 8 wks or longer experience with Fidelity120.
      Another three subjects exhibited initial decrements in spectral cue perception
      with Fidelity120 at the 8-wk time point; however, evidence from one subject
      suggested that such decrements may resolve with additional experience. Place
      pitch thresholds were inversely related to improvements in vowel F2 frequency
      perception with Fidelity120 relative to HiRes. However, no relationship was
      observed between place-pitch thresholds and the other spectral measures (vowel F1
      frequency or consonant place of articulation). CONCLUSIONS: Findings suggest that
      Fidelity120 supports small improvements in the perception of spectral speech cues
      in some Advanced Bionics CI users; however, many users show no clear benefit.
      Benefits are more likely to occur for vowel spectral cues (related to F1 and F2
      frequency) than for consonant spectral cues (related to place of articulation).
      There was an inconsistent relationship between place-pitch sensitivity and
      improvements in spectral cue perception with Fidelity120 relative to HiRes. This
      may partly reflect the small number of sites at which place-pitch thresholds were
      measured. Contrary to some previous reports, there was no clear evidence that
      Fidelity120 supports improved sentence recognition in noise.

PMID- 21084988
TI  - Endoscopic treatment of esophageal varices in advanced liver disease patients:
      band ligation versus cyanoacrylate injection.
AB  - BACKGROUND: The results of variceal band ligation (VBL) in patients with advanced
      liver disease are unknown. Cyanoacrylate injection (CI) might have a better
      outcome than VBL in the treatment of esophageal varices (EV) in these patients.
      AIM: To compare VBL and CI in the treatment of EV in patients with advanced liver
      disease. PATIENTS AND METHODS: Thirty-eight patients with medium or large EV and
      Child-Pugh index of at least eight were randomized into two groups: VBL (n=20)
      and CI (n=18). The patients were followed-up for at least 6 months after the end
      of treatment. Main outcomes were eradication, bleeding, mortality, complication,
      and recurrence rates. RESULTS: Variceal eradication rates were similar in the VBL
      and CI groups (90 vs. 72%, P=0.39). Mean number of sessions until eradication was
      3.17 and 3, respectively. Bleeding episodes until eradication were equally
      observed in both groups (P=0.17). Mortality (55 vs. 56%, P=0.52) and major
      complication rates (5 and 17%, P=0.32) were similar. Chest pain with dysphagia
      was more frequent in the CI group (55.6 vs. 10%, P=0.004). A higher risk of
      variceal recurrence was observed in the CI group (33 vs. 57%, P=0.04).
      CONCLUSION: No significant differences between the VBL and CI groups were
      observed in the treatment of EV in patients with advanced liver disease regarding
      mortality, variceal eradication, and major complications rates. However, minor
      complications and variceal recurrence were significantly more common in the CI
      group. In addition, there was a clear trend toward more bleeding episodes in
      patients included in the CI group.

PMID- 21084989
TI  - Mortality after surgery in patients with liver cirrhosis: comparison of Child
      Turcotte-Pugh, MELD and MELDNa score.
AB  - BACKGROUND/AIMS: This study was aimed at determining the postoperative mortality
      in patients with cirrhosis by Child-Turcotte-Pugh (CTP), Model for End-stage
      Liver Disease score (MELD), and Model for End-stage Liver Disease and Serum
      Sodium Concentration score (MELDNa) systems and to compare the predictability of
      the scoring systems. METHODS: Analysis was performed on clinical records of 490
      patients with cirrhosis who underwent surgery under general anesthesia from
      January 2003 to December 2008. RESULTS: (i) Ninety-day mortality in patients with
      CTP A, B, and C class were 2.1, 22.1 and 54.5%, respectively. (ii) Ninety-day
      mortality according to MELD score was as follows: 6-9, 3.5%; 10-14, 8.9%; 15-19,
      14.3%; 20-24, 12.5%; and >=25, 63.6%. (iii) Ninety-day mortality according to
      MELDNa score was as follows: 6-9, 1.9%; 10-14, 6.2%; 15-19, 13.2%; 20-24, 20.6%;
      and >=25, 50%. (iv) Multivariable analysis showed that emergency surgery,
      American Society of Anesthesiologist class >=IV, CTP score >=7, MELD score >=10,
      and MELDNa score >=10 were independent risk factors for 90-day mortality. (v) The
      area under the receiver operating curve of CTP, MELD, and MELDNa in predicting 90
      day mortality were 0.859, 0.761, 0.818, and nonparametric approach using the
      generalized U-statistic showed that the CTP score was equal to the MELDNa score
      (P=0.855) and the CTP and MELDNa scores were superior to the MELD score (P=0.027
      and 0.047) in predicting postoperative 90-day mortality. CONCLUSION: Mortality
      according to the CTP, MELD, and MELDNa scoring systems were determined and all
      scoring systems predicted postoperative mortality in patients with cirrhosis. The
      CTP score and MELDNa score were superior to the MELD score in predicting
      postoperative 90-day mortality.

PMID- 21084990
TI  - Distribution of antiretroviral treatment through self-forming groups of patients
      in Tete Province, Mozambique.
AB  - BACKGROUND: As antiretroviral treatment cohorts continue to expand, ensuring
      patient retention over time is an increasingly important concern. This, together
      with capacity and human resource constraints, has led to the consideration of out
      of-clinic models for the delivery of antiretroviral therapy (ART). In 2008,
      Medecins Sans Frontieres and the Provincial authorities launched a model of ART
      distribution and adherence monitoring by community groups in Tete Province,
      Mozambique. PROGRAMME APPROACH: Patients who were stable on ART for 6 months were
      informed about the community ART group model and invited to form groups. Group
      members had 4 key functions: facilitate monthly ART distribution to other group
      members in the community, provide adherence and social support, monitor outcomes,
      and ensure each group member undergoes a clinical consultation at least once
      every 6 months. Group members visit the health centre on a rotational basis, such
      that each group member has contact with the health service every 6 months.
      RESULTS: Between February 2008 and May 2010, 1384 members were enrolled into 291
      groups. Median follow-up time within a group was 12.9 months (IQR 8.5-14.1).
      During this time, 83 (6%) were transferred out, and of the 1301 patients still in
      community groups, 1269 (97.5%) were remaining in care, 30 (2%) had died, and 2
      (0.2%) were lost to follow-up. DISCUSSION: The Community ART Group model was
      initiated by patients to improve access, patient retention, and decongest health
      services. Early outcomes are highly satisfactory in terms of mortality and
      retention in care, lending support to such out-of-clinic approaches.

PMID- 21084991
TI  - Pandemic (H1N1) 2009 influenza virus seroconversion rates in HIV-infected
      individuals.
AB  - The impact of pandemic (H1N1) 2009 influenza in HIV-infected individuals is
      unknown. Determining the prevalence of pandemic influenza in this at-risk group
      will guide vaccination programs. After the first pandemic wave, the
      seroprevalence rate of pandemic influenza in HIV-infected individuals in western
      Sydney, New South Wales, Australia, was 34.2%, similar to the rate observed in
      the general population. However, true seroprevalence is more accurately
      determined by seroconversion, defined as a 4-fold or greater rise between
      preexposure and postexposure antibody levels, which was 14.6% in the present
      study. Seroconversion rates were independent of CD4 T-lymphocyte count and HIV
      plasma load. Neither HIV infection, nor severe immunosuppression, was a
      significant risk factor for pandemic influenza during the first southern
      hemisphere pandemic wave.

PMID- 21084992
TI  - An additive effect of protective host genetic factors correlates with HIV
      nonprogression status.
AB  - INTRODUCTION: In HIV-positive individuals, complex multifactorial mechanisms
      control viral infection. In addition to viral and immunological factors, the host
      genetic background also plays an important role. Our objective was to evaluate
      how various genetic factors associated with delayed AIDS onset. METHODS: Thirty
      HIV+ long-term nonprogressors (LTNPs) and 30 known progressors were analyzed.
      Host genes were analyzed in peripheral blood mononuclear cells DNA: CCR5 and HLA
      were polymerase chain reaction typed. HLA-C5', HCP5 polymorphisms, and CCL3L1
      copy number were determined using real-time polymerase chain reaction. RESULTS:
      The CCL3L1high-copy-CCR5 deletion genetic risk groups was overrepresented in
      LTNPs. However, separately, neither CCL3L1 nor CCR5 were significantly associated
      with clinical outcome. HLA seemed as a strong nonprogression determinant, mainly
      HLA-B and the less-studied HLA-C. HLA-Cw0102 and HLA-C5' had an impact on LTNP
      phenotype along with HLA-B5701 and B2705. The presence of allele combinations
      like HLA- B*5701-Cw0602, HLA-B*2705-Cw0102, or HLA-B*3801-Cw1203 had the
      strongest effect in non-progression. As for HCP5, no independent effect was
      observed. The studied factors had additive effects, and although the number of
      patients was small, it seemed that carrying a high number of protective alleles
      associated with progression delay. CONCLUSIONS: We showed the additive load of
      protective host factors was predictive of nonprogression, and that HLA-associated
      factors were predominant in this global effect.

PMID- 21084993
TI  - Who gets tested for HIV in a South African urban township? Implications for test
      and treat and gender-based prevention interventions.
AB  - BACKGROUND: With increasing calls for linking HIV-infected individuals to
      treatment and care via expanded testing, we examined sociodemographic and
      behavioral characteristics associated with HIV testing among men and women in
      Soweto, South Africa. METHODS: We conducted a cross-sectional household survey
      involving 1539 men and 1877 women as part of the community-randomized prevention
      trial Project ACCEPT/HPTN043 between July 2007 to October 2007. Multivariable
      logistic regression models, stratified by sex, assessed factors associated with
      HIV testing and then repeated testing. RESULTS: Most women (64.8%) and 28.9% of
      men reported ever having been tested for HIV, among whom 57.9% reported repeated
      HIV testing. In multivariable analyses, youth and students had a lower odds of
      HIV testing. Men and women who had conversations about HIV/AIDS with increasing
      frequency and who had heard about antiretroviral therapy were more likely to
      report HIV testing, and repeated testing. Men who had >= 12 years of education
      and who were of high socioeconomic status, and women who were married, who were
      of low socioeconomic status, and who had children under their care had a higher
      odds of HIV testing. Women, older individuals, those with higher levels of
      education, married individuals, and those with children under their care had a
      higher odds of reporting repeated HIV testing. Uptake of HIV testing was not
      associated with condom use, having multiple sex partners, and HIV-related stigma.
      CONCLUSIONS: Given the low uptake of HIV testing among men and youth, further
      targeted interventions could facilitate a test and treat strategy among urban
      South Africans.

PMID- 21084994
TI  - Attachment and fusion inhibitors potently prevent dendritic cell-driven HIV
      infection.
AB  - Dendritic cells (DCs) efficiently transfer captured (trans) or de novo-produced
      (cis) virus to CD4 T cells. Using monocyte-derived DCs, we evaluated entry
      inhibitors targeting HIV envelope (BMS-C, T-1249) or CCR5 (CMPD167) for their
      potency to prevent DC infection, DC-driven infection in T cells in trans and cis,
      and direct infection of DC-T-cell mixtures. Immature DC-T-cell cultures with
      distinct mechanisms of viral transfer yielded similar levels of infection and
      produced more proviral DNA compared with matched mature DC-T-cell cultures or
      infected immature DCs. Although all compounds completely blocked HIV replication,
      16 times more of each inhibitor (250 vs 15.6 nM) was required to prevent low
      level infection of DCs compared with the productive DC-T-cell cocultures. Across
      all cell systems tested, BMS-C blocked infection most potently. BMS-C was
      significantly more effective than CMPD167 at preventing DC infection. In fact,
      low doses of CMPD167 significantly enhanced DC infection. Elevated levels of CCL4
      were observed when immature DCs were cultured with CMPD167. Viral entry
      inhibitors did not interfere with Candida albicans-specific DC cytokine/chemokine
      responses. These findings indicate that an envelope-binding small molecule is a
      promising tool for topical microbicide design to prevent the infection of early
      targets needed to establish and disseminate HIV infection.

PMID- 21084996
TI  - Changes in programmatic outcomes during 7 years of scale-up at a community-based
      antiretroviral treatment service in South Africa.
AB  - OBJECTIVES: To assess sustainability of programmatic outcomes in a community
      based antiretroviral therapy (ART) service in South Africa during 7 years of
      scale-up. METHODS: Prospective cohort of treatment-naive patients aged >= 15
      years enrolled between 2002 and 2008. Data were analyzed by calendar period of
      ART initiation using time-to-event analysis and logistic regression. RESULTS: ART
      was initiated by 3162 patients (67% women; median age, 34 years) who were
      followed-up for a median of 2.4 years (interquartile range, 1.2-3.8). After 6
      years, the cumulative probability of death and loss to follow-up (LTFU) was
      37.4%. The probabilities of transfer-out to another ART service and of
      virological failure were 21.6% and 23.1%, respectively. Low mortality risk and
      excellent virological and immunological responses during the first year of ART
      were not associated with calendar period of ART initiation. In contrast, risk of
      LTFU and virological failure both increased between successive calendar periods
      in unadjusted and adjusted analyses. The number of patients per member of clinic
      staff increased markedly over time. CONCLUSIONS: Successful early outcomes (low
      mortality and good immunological and virological responses) were sustained
      between sequential calendar periods during 7 years of scale-up. In contrast, the
      increasing cumulative probabilities of LTFU or virological failure may reflect
      decreasing capacity to adequately support patients during long-term therapy as
      clinic caseload escalated.

PMID- 21084995
TI  - Pregnancy outcomes in women exposed to efavirenz and nevirapine: an appraisal of
      the IeDEA West Africa and ANRS Databases, Abidjan, Cote d'Ivoire.
AB  - BACKGROUND: An increasing number of HIV-infected women become pregnant while
      receiving efavirenz (EFV). We compared the pregnancy outcomes of women exposed to
      EFV and to nevirapine (NVP) during the first trimester. METHODS: A retrospective
      study in 4 HIV care centers participating to clinical trials and international
      cohort collaboration. All HIV-infected pregnant women who conceived on EFV-based
      or NVP-based antiretroviral therapy (ART) between 2003 and 2009 were included.
      Pregnancy outcomes were as follows: abortion (voluntary termination), miscarriage
      [unwanted termination <20 weeks of amenorrhea (WA)], stillborn (death >= 20 WA),
      preterm delivery (live-birth <37 WA), and low birth weight (LBW) (<2500 grams).
      RESULTS: Overall, 344 HIV-infected pregnant women conceived on ART (213 on EFV
      and 131 on NVP). Median age was 29 years, and median CD4 count 217 cells per
      microliter at ART initiation. The overall proportion was 11.7% for abortion, 5.2%
      for miscarriage, 6.7% for stillborn, 10.8% for preterm delivery, and 20.2% for
      LBW. There was no difference between EFV and NVP exposure, except for abortion
      (14.3% vs 7.3%; P = 0.05). No external and visible congenital malformation was
      observed neither in women exposed to EFV nor in women exposed to NVP.
      CONCLUSIONS: Among women exposed to EFV, no significant increased risk of
      unfavorable pregnancy outcome was reported except for abortion.

PMID- 21084998
TI  - Antiretroviral drugs in the cupboard are not enough: the impact of health
      systems' performance on mother-to-child transmission of HIV.
AB  - OBJECTIVE: To model the effect of health systems performance on rates of mother
      to-child HIV transmission. METHODS: We modeled the effect of variation in
      performance of the multiple steps of different prevention of mother-to-child
      transmission (PMTCT) protocols using hypothetical and reported data. SETTING:
      Data from a PMTCT program in a large province in South Africa was used to compare
      model predictions with reported outcomes for mother-to-child HIV transmission.
      MAIN OUTCOME MEASURE: Perinatal HIV transmission was predicted for infants of 6
      weeks of age. RESULTS: HIV-infected pregnant women who fulfill eligibility
      criteria are initiated on lifelong antiretroviral treatment, whereas noneligible
      HIV-infected women and their infants receive single-dose nevirapine in a health
      system functioning at reported performance levels, and the overall vertical
      transmission rate would be 19.5%. Adding azidothymidine for women not eligible
      for lifelong treatment would further decrease the overall transmission rates only
      marginally to 17%. If the same steps were accomplished at 95% reliability, then
      the overall transmission rates would be 9.4% and 4.1%, respectively. CONCLUSIONS:
      Introduction of more effective combination antiretroviral interventions will
      yield only marginal reductions in childhood HIV infections and mortality unless
      health systems achieve high levels of performance at each step of the PMTCT
      pathway. Investment in and support for the mechanisms of delivering and
      sustaining PMTCT interventions at scale are required if gains in maternal and
      child survival are to be realized in countries highly affected by HIV.

PMID- 21084997
TI  - Risk factors influencing antibody responses to Kaposi's sarcoma-associated
      herpesvirus latent and lytic antigens in patients under antiretroviral therapy.
AB  - BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) seropositivity and
      lytic antibody titer are predictors for Kaposi's sarcoma. METHODS: We examined
      demographic, viral, and immunologic factors that influence KSHV latent and lytic
      antibodies in HIV-infected patients. RESULTS: Detection rate of KSHV latent but
      not lytic antibodies was lower in patients with CD4 cells/mm3 less than 200 than
      greater than 200 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.11-0.61)
      and CD8 cells/mm3 less than 400 than greater than 400 (OR, 0.26; 95% CI, 0.07
      0.67). Overall seropositivity rate was higher in patients with CD4 cells/mm3 less
      than 200 than greater than 200 (OR, 2.34; 95% CI, 1.37-4.02) and HIV copies/mL
      greater than 400 than less than 400 (OR, 1.70; 95% CI, 1.09-2.65). Lytic antibody
      level was inversely correlated with CD4 count (P < 0.001). Lytic seropositivity
      (OR, 2.47; 95% CI, 1.35-4.50) and antibody level (adjusted difference mean
      optical density, 0.324; 95% CI, 0.16-0.46) were higher in patients with HIV
      infection greater than 15 than less than 15 years. Hispanics had higher lytic
      seropositivity rate (OR, 1.71; 95% CI, 1.07-2.73) and antibody level (adjusted
      difference mean optical density, 0.111; 95% CI, 0.03-0.18) than non-Hispanics.
      CONCLUSIONS: Lower CD4 and CD8 counts impair antibody response to KSHV latent
      antigens. Immune deterioration, long-term HIV infection, and Hispanic status are
      risk factors for Kaposi's sarcoma predictors.

PMID- 21084999
TI  - Male antenatal attendance and HIV testing are associated with decreased infant
      HIV infection and increased HIV-free survival.
AB  - OBJECTIVE: To investigate the relationship between male involvement in prevention
      of mother-to-child HIV transmission services and infant HIV acquisition and
      mortality, a prospective cohort study was undertaken between 1999 and 2005 in
      Nairobi, Kenya. METHODS: HIV-infected pregnant women were enrolled and followed
      with their infants for 1 year with infant HIV DNA testing at birth, 1, 3, 6, 9,
      and 12 months postpartum. Women were encouraged to invite male partners for
      prevention counseling and HIV testing. RESULTS: Among 456 female participants,
      140 partners (31%) attended the antenatal clinic. Eighty-two (19%) of 441 infants
      tested were HIV infected by 1 year of age. Adjusting for maternal viral load,
      vertical transmission risk was lower among women with partner attendance compared
      with those without [adjusted hazard ratio (aHR) = 0.56, 95% confidence interval
      (CI): 0.33 to 0.98; P = 0.042] and among women reporting versus not reporting
      previous partner HIV testing (aHR = 0.52, 95% CI: 0.32 to 0.84; P = 0.008). The
      combined risk of HIV acquisition or infant mortality was lower with male
      attendance (aHR = 0.55; 95% CI: 0.35 to 0.88; P = 0.012) and report of prior male
      HIV testing (aHR = 0.58; 95% CI: 0.34 to 0.88; P = 0.01) when adjusting for
      maternal viral load and breastfeeding. CONCLUSIONS: Including men in antenatal
      prevention of mother-to-child HIV transmission services with HIV testing may
      improve infant health outcomes.

PMID- 21085001
TI  - Pretreatment with different loading doses of clopidogrel influences P-selectin
      levels in patients undergoing percutaneous coronary intervention: results from
      the ARMYDA-2 (antiplatelet therapy for reduction of myocardial damage during
      angioplasty) SELECT substudy.
AB  - OBJECTIVES: ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage
      during Angioplasty) trial demonstrated improved clinical outcome in patients
      undergoing percutaneous coronary intervention (PCI) pretreated with 600 vs. 300
      mg clopidogrel loading dose. ARMYDA-2 SELECT is a prospectively planned
      subanalysis to investigate the effects of those different loading regimens on P
      selectin levels. METHODS: From the ARMYDA-2 population, we investigated a
      subgroup of 84 patients (41 randomized to a 600 mg and 43 to a 300 mg clopidogrel
      loading dose given at a mean time of 6 h before PCI), in whom soluble P-selectin
      levels were measured at baseline (at the time of clopidogrel administration),
      immediately after the procedure, and after 8 and 24 h. RESULTS: In the overall
      study population, a significant decrease of P-selectin levels was observed from
      baseline to intervention (from 91 +/- 10 to 53 +/- 15 ng/ml; P < 0.001). Baseline
      P-selectin levels were similar in the two groups, whereas at the time of
      intervention they were significantly lower in the high-dose arm (50 +/- 13 vs. 58
      +/- 15 ng/ml; P = 0.048). P-selectin values between the two arms were not
      different at the subsequent determinations. The lowest procedural P-selectin
      levels were observed in patients of the 600 mg arm who had no postprocedural
      increase of troponin-I above normal limits (P <= 0.040). CONCLUSION: Pretreatment
      with clopidogrel before PCI decreases peri-procedural P-selectin levels;
      moreover, a 600 mg clopidogrel loading dose, compared with the 300 mg regimen, is
      associated with reduction of peri-procedural myocardial damage and significant
      attenuation of P-selectin levels at the time of intervention. These results may
      help in identifying mechanisms underlying clinical benefit of the high
      clopidogrel load in PCI.

PMID- 21085000
TI  - Intraventricular conduction disturbances and paroxysmal atrioventricular block in
      a young patient with MELAS.
AB  - We present the case of a 36-year-old male patient with MELAS (mitochondrial
      encephalomyopathy, lactic acidosis and stroke-like episodes) who developed
      intraventricular conduction disturbances and syncopal episodes due to a
      paroxysmal atrioventricular block. This case suggests that in MELAS, as well as
      in other mithochondriopathies, intraventricular conduction disturbances and
      atrioventricular block can be features of the disease. In our case, progression
      toward atrioventricular block was rapid, suggesting that in MELAS patients
      presenting with worsening conduction system anomalies, pacemaker implantation has
      to be considered without delay, irrespective of age. 

PMID- 21085002
TI  - Severe acute left ventricular dysfunction in multiple sclerosis.

PMID- 21085003
TI  - Stent-triggered 'electric shock' during leg bending 2 years after emergency iliac
      artery percutaneous revascularization.
AB  - We report a case of a 41-year-old woman who underwent surgical removal of an
      uterine leiomyoma, complicated by accidental injury of the left external iliac
      artery, treated by suturing. A few days after the intervention the patient was
      treated with emergency percutaneous stent implantation for acute thrombotic
      occlusion of the external iliac artery. Two years later, the patient began to
      complain of pain in the left leg, as an 'electric shock' sensation in the leg
      during squatting and leg adduction on the trunk. An angiographic control showed a
      critical in-stent restenosis at the level of a misplaced stent. Thus the patient
      was submitted to surgical exploration and stent removal.

PMID- 21085004
TI  - Sinus escape-capture bigeminy alternating with sinus extrasystolic bigeminy: dual
      atrial response and apparent sinus escape.
AB  - We report here five cases of sinus bigeminy in which comparatively long PP
      intervals alternated with comparatively short PP intervals, suggesting 'sinus
      escape-capture bigeminy' or 'sinus extrasystolic bigeminy'. In three of the
      cases, these two forms of sinus bigeminy were found in the same patient. This is
      the first study on 'sinus escape-capture bigeminy' alternating with 'sinus
      extrasystolic bigeminy'. The electrocardiographic findings in these cases suggest
      the possibility that 'sinus escape' in the sinoatrial junction is not true
      escape. Attempts are made to explain that apparent sinoatrial junctional escape
      occurs as a result of markedly slow conduction through the slow sinoatrial
      pathway, using the concepts of 'dual sinoatrial pathways' and 'double atrial
      response'.

PMID- 21085005
TI  - Diagnosis of unicommissural unicuspid aortic valve stenosis by different imaging
      modalities.
AB  - A 32-year-old woman was admitted to our institution for further evaluation of
      aortic stenosis. Diagnosis of severe aortic stenosis was made by transthoracic
      echocardiography. Transesophageal echocardiography, live three-dimensional
      echocardiography and cardiovascular MRI allowed precise evaluation of valve
      morphology. Interestingly, valve morphology was unicuspid unicommissural with a
      posterior funnel-shaped valve opening. Surgical inspection during valve
      replacement confirmed the diagnosis of an unicuspid aortic valve. This case
      report highlights the use of different imaging modalities in characterizing
      aortic valve morphology.

PMID- 21085006
TI  - Clinical characteristics and mortality of hospitalized alcoholic hepatitis
      patients in the United States.
AB  - BACKGROUND AND AIMS: Alcoholic hepatitis (AH) is the most florid manifestation of
      alcoholic liver disease. In this study, we examined the clinical characteristics
      and risk factors associated with mortality in hospitalized AH patients in the
      United States using the 2007 Nationwide inpatient sample of the Healthcare Cost
      and Utilization Project. METHODS: Patients who were hospitalized with the primary
      diagnosis of AH in the United States in 2007 were identified using International
      Classification of Diseases-9 code. We further characterized these subjects based
      on associated symptoms (such as ascites, hepatic encephalopathy, and
      coagulopathy), complications during hospitalization (such as sepsis, pneumonia,
      spontaneous bacterial peritonitis, and acute renal failure), and categories
      pertaining to hospital characteristics, such as teaching status. The predictors
      of mortality were calculated using logistic regression analyses. RESULTS: There
      were 8,043,415 in-patient admissions, of which 56,809 (0.71%) were hospitalized
      with the primary diagnosis of AH. The mean age was 53.2 years, and 27% were
      female. The average length of stay was 6.5+/-7.7 days and 3,881 subjects (6.8%)
      died during hospitalization. Medicare and Medicaid were the main primary expected
      payer sources (51.8%) with the average total charges during hospital stay of
      $37,769. In the multivariate analyses, older age, presence of sepsis, spontaneous
      bacterial peritonitis, pneumonia, urinary tract infection, acute renal failure,
      hepatic encephalopathy, and coagulopathy were independently associated with in
      patient mortality. CONCLUSIONS: In-hospital mortality rate for AH remains high,
      especially in those with infectious complications, hepatic encephalopathy,
      coagulopathy, and acute renal failure. Our analysis documented significant
      healthcare cost and utilization among hospitalized AH patients.

PMID- 21085008
TI  - The management of gastrointestinal disease in Hermansky-Pudlak syndrome.
AB  - Hermansky-Pudlak syndrome (HPS) was first described in 1959 by Hermansky and
      Pudlak. Clinically, HPS is characterized by oculocutaneous albinism, platelet
      storage pool deficiency, and ceroid tissue accumulation. It is a rare disorder
      that has been described globally but has the highest frequency in a cluster
      population in Puerto Rico. HPS patients also have major organ involvement that
      typically includes pulmonary fibrosis and granulomatous colitis. Rarely have
      cardiomyopathy and renal dysfunction been described. We report a case of the
      oldest historical patient with HPS type 6 and the associated gastrointestinal
      management.

PMID- 21085009
TI  - Outcome of patients with systemic rheumatic diseases admitted to a medical
      intensive care unit.

PMID- 21085007
TI  - Reduced polyp detection as endoscopy shift progresses: experience with screening
      colonoscopy at a tertiary-care hospital.
AB  - GOALS: To determine whether polyp detection rates are reduced as time progresses
      through half and full-day endoscopy shifts. BACKGROUND: Polyp detection on
      colonoscopy may be reduced during colonoscopies performed later in the day.
      STUDY: Retrospective analysis of screening colonoscopies performed by attending
      physicians only between August 2003 and August 2005 at University of North
      Carolina Hospitals. The primary outcome was detection of any polyp. The secondary
      outcome was adenoma detection. Both were assessed by time of day and shift type.
      RESULTS: A total of 3421 eligible screening colonoscopies, performed by 20
      attending gastroenterologists, were analyzed. Polyp detection rate for
      colonoscopies initiated before 9 AM was 48.6%, versus 34.0% for those initiated
      after 4:00 PM (P=0.04). On multivariate analysis, each hour of the day was
      associated with reduced odds of polyp detection [adjusted odds ratio (OR) 0.93,
      95% confidence interval (CI) 0.89-0.98 for any polyp; adjusted OR: 0.94, 95% CI:
      0.89-0.98 for adenoma]. When evaluated by physician shift, the odds of polyp
      detection were reduced in the last 1.5 hours compared with the first 1.5 hours of
      the shift, regardless of the length or timing of the shift (AM shift: OR: 0.63,
      95% CI: 0.41-0.96; PM shift: OR: 0.79, 95% CI: 0.42-1.46; and full-day shift: OR:
      0.67, 95% CI: 0.44-1.00). CONCLUSIONS: Polyp detection by attending tertiary-care
      gastrointestinal physicians is reduced as time progresses during both half and
      full-day endoscopy shifts. These findings have implications for future quality
      improvement interventions.

PMID- 21085010
TI  - Asymptomatic gout in a male with meniscus injury.

PMID- 21085011
TI  - Intravenous methylprednisolone can cause an acute, vision-threatening rise in
      intraocular pressure.

PMID- 21085012
TI  - Polyarticular palindromic syndrome due to lues infection.

PMID- 21085013
TI  - Primary bone lymphoma: polyostotic disease presenting as a cauda equina syndrome.
AB  - We report a patient with B-cell primary bone lymphoma with involvement of
      multiple vertebrae at presentation and rapid development of cauda equina
      syndrome. The patient presented subacute low-back pain, initially with good
      response to corticosteroid treatment.Primary bone lymphoma is a very unusual
      disease, commonly affecting only 1 vertebra. Despite this, our case involved
      multiple levels at the onset; furthermore, there were no adenopathies. Because of
      the information of the magnetic resonance imaging, an open biopsy of the
      vertebrae was performed for diagnosis. The reported cases of radicular syndromes
      secondary to a lymphoma as an initial symptom are extremely infrequently reported
      in the literature, above all for a B-cell lymphoma.

PMID- 21085014
TI  - Testicular pain followed by microscopic hematuria, a renal mass, palpable
      purpura, polyarthritis, and hematochezia.
AB  - We present the instructive case of a man who developed progressively severe
      testicular pain. He sought the medical care of several physicians, including
      general medicine, urology, and rheumatology. What began with focal testicular
      pain evolved over the ensuing weeks to a multisystem disorder affecting at least
      3 additional organ systems beyond the genitourinary tract. Leukocytoclastic
      vasculitis was diagnosed, affecting the skin, joints, kidney, and
      gastrointestinal tract with predominant IgA deposition consistent with underlying
      Henoch-Schonlein purpura in the setting of renal cell carcinoma. This case
      illustrates and reinforces both the importance of considering an occult
      malignancy in a patient who presents with symptoms suggestive of a systemic
      vasculitis as well as the importance of considering an occult vasculitis in the
      adult male patient presenting with testicular pain.

PMID- 21085015
TI  - Biopsy diagnosis of early myositis ossificans without radiologic evidence of
      calcification: success of early surgical resection.
AB  - Myositis ossificans is an uncommon disorder, which is commonly mistaken for a
      malignant muscle disease before histologic examination. Trauma is the most common
      cause of the acquired form of the disease; however, atraumatic cases have been
      described. The factors responsible for extraosseous ossification, such as the
      role of bone morphogenic protein 4, are becoming better understood. However,
      treatment of the disorder is not well defined. We present a case of atraumatic
      myositis ossificans in a 16-year-old girl that was associated with severe pain
      and lacked radiologic evidence of calcification. She underwent early surgical
      excision, resulting in immediate resolution of her symptoms. This case
      demonstrates that waiting for complete maturation of the lesion may not be
      necessary.

PMID- 21085016
TI  - Necrotizing fasciitis and myositis caused by streptococcal flesh-eating bacteria.
AB  - Three types of group A streptococcal infections are particularly feared:
      necrotizing fasciitis, myositis, and streptococcal toxic shock syndrome (TSS). We
      present 3 cases of necrotizing fasciitis due to Streptococcus pyogenes, one in an
      immunocompromised patient who had received kidney transplant and 2 healthy
      patients. Mean age of patients was 52 years (range, 42-67 years), and all 3 were
      male. One spontaneous case in absence of any obvious portal of entry is reported.
      The clinical course was initially indolent but quickly destructive. All patients
      required emergency surgical debridement and intravenous antibiotics. In 2 cases,
      intravenous immunoglobulin therapy was added. Differential diagnoses include
      septic arthritis, cellulitis, gout, other causes of tenosynovitis, erysipelas,
      and deep vein thrombosis.Blood and soft-tissue cultures should be obtained to
      identify the bacteria, and emergency computed tomography or magnetic resonance
      imaging scan should be performed to confirm the diagnosis and define the
      extension of the necrosis. Aggressive surgical debridement in the first 24 to 48
      hours and antibiotic treatment, including penicillin and clindamycin, are the
      cornerstones in the management of these infections. Adjuvant intravenous
      immunoglobulin therapy might be useful in case of TSS. Diagnostic and treatment
      delays are the main causes of mortality in these infections.

PMID- 21085017
TI  - Benign spontaneous pneumoperitoneum in systemic sclerosis.
AB  - The gastrointestinal tract is commonly involved in patients with systemic
      sclerosis (SSc) (Am J Gastroenterol. 1972;58:30-44). Intestinal manifestations of
      SSc include impaired motility, malabsorption, bacterial overgrowth, jejunal and
      wide-mouthed colonic diverticuli, localized dilatation, pseudo-obstruction, and,
      less commonly, pneumatosis cystoides intestinalis (PCI) (Rheumatology.
      2009;48:iii36-iii39; J Clin Gastroenterol. 2008;42:5-12). Benign spontaneous
      pneumoperitoneum is a rare complication of SSc and is often associated with PCI
      (Mo Med. 1967;64:117-118). We report a case of spontaneous pneumoperitoneum
      without evidence of peritoneal irritation in a malnourished patient with long
      standing SSc. Computed tomography scan of the abdomen and pelvis on admission
      revealed pneumoperitoneum with PCI without visceral perforation. Subsequent
      imaging revealed the persistence of the pneumoperitoneum with resolution of the
      PCI. It is important for the clinician to recognize benign spontaneous
      pneumoperitoneum as a possible complication in patients with SSc and to be able
      to differentiate this from a ruptured viscus with peritonitis based on clinical
      presentation. The management of benign spontaneous pneumoperitoneum is
      supportive, thereby avoiding unnecessary surgery.

PMID- 21085018
TI  - The safety and effectiveness of a chloroform/methanol extract of Tripterygium
      wilfordii Hook F (T2) plus methotrexate in treating rheumatoid arthritis.
AB  - OBJECTIVES: The objective of the study was to assess the safety and effectiveness
      of the chloroform/methanol extract of Tripterygium wilfordii Hook F (T2) plus
      methotrexate (MTX) in treating patients with rheumatoid arthritis (RA). METHODS:
      One hundred sixty-six patients with RA, who started the combination therapy of T2
      (20 mg b.i.d. or t.i.d.) and MTX (10-12.5 mg/wk), were enrolled, and these
      patients were followed up for at least 1 year. Demographics, disease severity,
      markers of disease activity before and after the combination therapy, and
      incidence of adverse events were evaluated. RESULTS: The patients were
      predominantly female (n = 134, 81%) with a mean age of 58.0 (SD, 7.9) years
      (range, 39-79 years) and a mean disease duration of 55.0 (SD, 72.2) months
      (range, 0-456 months). A total of 161, 161, 146, and 85 patients had received at
      least 1, 3, 12, and 24 months of the combination of T2 and MTX, with a total of
      4162 patient-months' exposure to the combination therapy. The combination therapy
      reduced tender and swollen joint counts, morning stiffness, inflammatory indices
      such as ESR and CRP, and improved disease activity as measured by the DAS28
      significantly by 3 months as well as 12 months (P < 0.05). Most of the adverse
      events noted during this study were mild. Menstrual irregularity occurred in
      72.7% (16/22) of premenopausal female. Only 10 (6.0%) and 8 (4.8%) subjects
      withdrew because of adverse events or lack of efficacy, respectively. Severe
      infections were very rare. CONCLUSION: T2 plus MTX is an effective and relatively
      safe treatment for RA patients.

PMID- 21085019
TI  - Observational cross-sectional study revealing less aggressive treatment in
      Japanese elderly than nonelderly patients with rheumatoid arthritis.
AB  - BACKGROUND: Elderly patients with rheumatoid arthritis (RA) have more aging
      related complications than nonelderly patients with RA. OBJECTIVES: The objective
      of the study was to investigate the treatment status of elderly patients with RA.
      METHODS: Between January and March 2008, 969 patients with RA were enrolled in
      this observational cross-sectional study. Prescription of disease-modifying
      antirheumatic drugs (DMARDs) and corticosteroids and laboratory data related to
      RA, including matrix metalloproteinase 3, rheumatoid factor, and anti-cyclic
      citrullinated peptide antibody levels, were compared between the elderly and the
      nonelderly patients. RESULTS: Fewer DMARDs were prescribed to the elderly
      patients (1.40 [SD, 0.57] vs. 1.51 [SD, 0.61]; P = 0.029). Furthermore, a lower
      percentage of patients received methotrexate (MTX) (47.2% vs. 56.9%; P = 0.0001),
      a lower average dosage of MTX was administered (5.46 [SD, 1.66] mg/wk vs. 5.96
      [SD, 1.77] mg/wk; P = 0.0001), and fewer biologic DMARDs were used (1.46% vs.
      5.59% for infliximab, P = 0.0008; 0.58% vs. 3.19% for etanercept, P = 0.0038) in
      the elderly group. The laboratory data suggested that the disease status was
      uncontrolled to a greater extent, and complications were more common in the
      elderly group. CONCLUSION: Elderly patients with RA receive less aggressive
      treatment than nonelderly patients with RA, despite laboratory evidence for
      poorly controlled disease status among the elderly. The use of a less aggressive
      regimen could be attributed to the higher prevalence of complications and
      problems. Therefore, the elderly with RA should be considered a different patient
      population from the viewpoint of treatment and be administered specialized
      medical care.

PMID- 21085020
TI  - Evaluation of 25-hydroxyvitamin D serum levels in patients with fibromyalgia.
AB  - BACKGROUND: Fibromyalgia (FM) is a condition characterized by chronic widespread
      musculoskeletal pain often associated with sleep disorders and mood and whose
      pathophysiology is still not clearly defined. In recent years, some studies have
      hinted at a possible association between different types of pain, including the
      pain present in FM, with vitamin D deficiency. OBJECTIVE AND METHODS: The present
      work consisted of a cross-sectional study aimed at evaluating 25-hydroxyvitamin D
      (25(OH)D) serum levels in 87 patients with FM, as compared with a control group
      composed of 92 age- and sex-matched subjects with no chronic musculoskeletal
      pain. Clinical and laboratory variables that could affect the status of vitamin D
      were also considered. RESULTS: There was no statistically significant difference
      between groups either with respect to mean serum concentration of 25(OH)D or as
      to the classification of levels as deficient, insufficient, or sufficient. There
      was no correlation of 25(OH)D levels with pain intensity. CONCLUSION: This study
      showed that light to moderate deficient and insufficient 25(OH)D levels are not
      found more commonly in patients with FM.

PMID- 21085021
TI  - Screening for low literacy in a rheumatology setting: more than 10% of patients
      cannot read "cartilage," "diagnosis," "rheumatologist," or "symptom".
AB  - OBJECTIVES: The objectives of the study were to analyze literacy in 194
      consecutive patients at an academic rheumatology setting with the Rapid Estimate
      of Adult Literacy in Medicine (REALM) and an "Arthritis-Adapted" REALM (A-REALM),
      and to compare responses to one another and to demographic and clinical measures.
      METHODS: The REALM and A-REALM are two 66-item word recognition tests. Both were
      administered to 194 consecutive patients in usual rheumatology care.
      Multidimensional Health Assessment Questionnaire (MDHAQ) scores for physical
      function, pain, fatigue, and global estimate, and laboratory assessments also
      were available. Descriptive statistics and analyses of agreement were computed.
      RESULTS: REALM and A-REALM administration involved 2 to 3 minutes each. Scores
      below 61, indicating a reading level at eighth grade or less, were seen in 35
      (18%) of 194 patients on the REALM and 46 patients (24%) on the A-REALM. No
      patient was classified as having severely low literacy at or below a third-grade
      level. However, words not read correctly by 10% or more of the patients on the
      REALM included diagnosis (14%), osteoporosis (17%), and inflammatory (10%), and
      on the A-REALM, rheumatologist (11%), cartilage (14%), and symptom (14%). REALM
      and A-REALM scores were correlated significantly (Pearson r = 0.94, P < 0.001).
      Almost all patients (33/35) with REALM scores of less than 61 also had A-REALM
      scores of less than 61, less formal education, and poorer clinical status on all
      measures, most not statistically significant. CONCLUSION: Low literacy is an
      important underrecognized problem in medical care, which may be assessed easily
      in standard care using the REALM or A-REALM. Further attention to literacy
      associated barriers may reduce socioeconomic disparities in health.

PMID- 21085022
TI  - Pediatric complex divergent elbow dislocation.
AB  - A divergent dislocation of the elbow is a very rare injury, and only a few cases
      have been described in the literature. It is characterized as a dorsal
      dislocation of the ulnohumeral joint combined with a lateral dislocation of the
      proximal radius. All three articulations of the elbow joint are involved. Like in
      our case, it can be accompanied by an avulsion fracture of the coronoid and a
      distal radius fracture. For correct understanding of the injury, proper
      radiographic studies are imperative. In contrast to some earlier reports that
      advise a conservative approach, we performed a very aggressive operative
      treatment. To ensure anatomic reconstruction of the elbow, surgical exposure of
      the various injuries was performed first. After gross reduction of the joint
      dislocation, definitive osteosynthesis of the distal radius fracture was
      performed. Subsequently, the coronoid process and lateral collateral ligament
      could be repaired anatomically, improving the stability of the elbow. An
      uneventful recovery with excellent elbow motion and stability was achieved.

PMID- 21085023
TI  - Dual plating for fractures of the distal third of the humeral shaft.
AB  - In this study, we present a novel method for performing dual plating of extra
      articular fractures of the distal third of the humerus. Since 2006, we have
      treated 15 such fractures with dual plates from a single posterior midline
      incision. In the first part of the study, we provide the surgical protocol we
      have used in addressing these fractures. In the second part, the charts of these
      patients were reviewed retrospectively to examine their clinical and radiographic
      outcomes. Using this technique, we have achieved an excellent union rate without
      significant complications while allowing early and aggressive range of motion.

PMID- 21085025
TI  - Divergent elbow dislocation in the very young child: easily treated if correctly
      diagnosed.
AB  - We report a case of a 3-year-old boy that sustained a divergent elbow dislocation
      and was treated appropriately once the diagnosis was established. The purpose of
      this report is to bring attention to this rare injury.

PMID- 21085024
TI  - Use of flexion and extension radiographs of the cervical spine to rule out acute
      instability in patients with negative computed tomography scans.
AB  - OBJECTIVES: To investigate the usefulness of flexion and extension radiographs of
      the cervical spine as a screening tool for the acute evaluation of ligamentous
      injury in cases of awake blunt trauma in patients with a negative cervical
      computed tomography scan. STUDY DESIGN: Retrospective study of consecutive
      patient series. SETTING: Level I trauma center. PATIENTS: All patients admitted
      to an academic Level I trauma center over 12 months who sustained a blunt force
      injury and underwent flexion-extension radiography during hospitalization.
      INTERVENTION: The flexion-extension radiographs were interpreted for adequacy and
      pathology by two independent reviewers who were blinded to patient outcome and
      the original radiologic interpretation. Adequacy of radiographs was assessed
      using four criteria: 1) complete visualization of the cervical spine from the
      occiput to the superior end plate of the first thoracic vertebra; 2) adequate
      range of flexion and extension was defined as motion greater than 30 degrees 
      from the neutral position; 3) supplementation with a swimmer's view if the
      cervicothoracic junction was poorly visualized; and 4) no evidence of rotational
      deformity on neutral, flexion, or extension views. Radiographs were thus deemed
      either "adequate" or "inadequate." Acute instability was defined as listhesis of
      greater than 3.5 mm or 11 degrees  of relative angulation. Radiologists'
      interpretation of all studies was noted and any clinical or radiographic evidence
      of instability on follow-up within 3 months of discharge was also recorded.
      RESULTS: A total of 311 patients were included in the study. The intraobserver
      reliability for the four fixed criteria for adequacy of flexion and extension
      radiographs was excellent. Only 97 (31%) flexion and extension radiographs were
      deemed adequate. Two hundred fourteen (69%) patient radiographs were deemed
      inadequate but were interpreted as normal by the radiologists. Not a single
      radiograph was identified with evidence of acute instability (true-positive = 0).
      One hundred seventy-one (55%) of patients had follow-up within 3 months of
      discharge from the hospital of which one (0.5%) patient developed signs of
      instability necessitating surgery. The sensitivity was 0%, specificity 99%,
      positive predictive value 0%, and negative predictive value 31%. CONCLUSION:
      Flexion and extension radiographs do not appear to be clinically useful in
      assessing acute instability in patients hospitalized with blunt trauma with
      negative computed tomography scans.

PMID- 21085026
TI  - Radiographic outcomes after treatment of pediatric supracondylar humerus
      fractures using a treatment-based classification system.
AB  - OBJECTIVES: To develop a radiographic method to categorize supracondylar
      fractures into four types that have logical treatment correlations. The new
      classification is described, illustrated, and then tested to see if it is
      reproducible, safe, and effective. DESIGN: Clinical follow-up study. SETTING:
      Level I trauma center. PATIENTS: One hundred forty-one extension-type
      supracondylar fractures. INTERVENTION: According to our system, a long arm cast
      without reduction was indicated for no or little displacement (Type I), closed
      reduction and long arm casting was indicated for minimal displacement (Type II),
      closed reduction and lateral pinning was indicated for moderate displacement
      (Type III), and closed or open reduction and medial-lateral crossed pinning was
      indicated for complete displacement (Type IV). MAIN OUTCOME MEASURE: Baumann's
      angle (anteroposterior) and the shaft-condylar angle (lateral). RESULTS: : No
      significant differences were observed among the four types with respect to
      changes in Baumann's angle or the shaft-condylar angle. No patient experienced a
      major loss of reduction and no iatrogenic ulnar nerve injury was encountered.
      CONCLUSIONS: The described treatment-based classification of extension-type
      supracondylar humerus fractures demonstrates promising results.

PMID- 21085027
TI  - Supracondylar fractures with circulatory failure after reduction, pinning, and
      entrapment of the brachial artery: excellent results more than 1 year after open
      exploration and revascularization.
AB  - OBJECTIVES: Neurovascular injuries in children with dislocated supracondylar
      humeral fractures are not uncommon. Closed reduction and pin fixation usually
      will restore the circulation. In some patients, there is still compromised
      circulation and a neurologic deficit, and they are treated with open exploration
      and microvascular reconstruction. We have investigated the clinical and
      functional outcome more than 1 year after the injury in this most serious group
      of patients. DESIGN: Retrospective follow-up study. PATIENTS: During 2001 to
      2007, five patients were referred to our department with a pale, pulseless hand
      and circulatory impairment with absent or slow capillary refill after primary
      treatment with closed reduction and cross pinning at their local hospital for
      Gartland Type III supracondylar fractures. Two of the patients also had clinical
      signs of nerve injury. INTERVENTION: All were reoperated on with open exploration
      and release of the entrapped brachial artery. Vascular reconstruction was
      performed in four patients (vasodilating agent was sufficient in one patient) and
      release of the median nerve from the fracture in two. One of these two also had a
      Kirschner wire pierced through the ulnar nerve. All fractures were rereduced and
      cross-pinned. No intra- or postoperative complications were seen.
      OUTCOME/RESULTS: At follow-up more than 1 year after the injury, all patients
      exhibited normal and symmetric function in their upper extremities, including
      circulation, neurologic status, range of motion, grip strength, and key pinch
      strength. Clinical and radiologic appearance was normal. CONCLUSION: Pulseless
      arms after repositioning of dislocated supracondylar humeral fractures are a
      medical emergency. After open release and, if necessary, microvascular
      reconstruction of vessels and nerves, fracture reduction, and fixation, excellent
      clinical long-term outcome can be expected. The procedure can be carried out with
      a low rate of complications.

PMID- 21085028
TI  - Biomechanical analysis of fixation of middle third fractures of the clavicle.
AB  - OBJECTIVE: This biomechanical study compares four different techniques of
      fixation of middle third clavicular fractures. METHODS: Twenty fresh-frozen
      clavicles were randomized into four groups. Each group used a different fixation
      device (3.5 Synthes reconstruction plate, 3.5 Synthes limited contact dynamic
      compression plate, 3.5 Synthes locking compression plate, and 4.5 DePuy Rockwood
      clavicular pin). All constructs were mechanically tested in bending and torque
      modes both with and without a simulated inferior cortical defect. Bending load to
      failure was also conducted. The four groups were compared using an analysis of
      variance test. RESULTS: The plate constructs were stiffer than the pin during
      both pure bending and torque loads with or without an inferior cortical defect.
      Bending load to failure with an inferior cortical defect revealed that the
      reconstruction plate was weaker compared with the other three groups. The limited
      contact and locking plates were stiffer than the reconstruction plate but
      demonstrated statistical significance only with the cortical defect. CONCLUSIONS:
      As hypothesized, the 3.5 limited contact dynamic compression plate and 3.5
      locking compression plate demonstrated the greatest resistance to bending and
      torque loads, especially in the presence of simulated comminution of a middle
      third clavicular fracture. The reconstruction plate demonstrated lower stiffness
      and strength values compared with the other plates, especially with a cortical
      defect, whereas the pin showed poor resistance to bending and torque loads in all
      modes of testing. This information may help surgeons to choose the most
      appropriate method of fixation when treating fractures of the middle third of the
      clavicle.

PMID- 21085029
TI  - Biomechanical comparison of locking versus nonlocking volar and dorsal T-plates
      for fixation of dorsally comminuted distal radius fractures.
AB  - OBJECTIVES: The purpose of this study was to gain insight into the effect of
      plate location and screw type for fixation of extra-articular distal radius
      fractures with dorsal comminution (Orthopaedic Trauma Association Type 23-A3.2).
      METHODS: Sixteen pairs of cadaver radii were randomized to four plating
      configurations: dorsal locking, dorsal nonlocking, volar locking, and volar
      nonlocking. A standard 1-cm dorsal wedge osteotomy was used. Cyclic axial loads
      were applied for 5000 cycles. Stiffness and fragment displacement were recorded
      at 500 cycle-intervals. Pre- and postcyclic loading radiographs were analyzed. An
      axial load to failure test followed and construct stiffness and failure strength
      recorded. Biomechanical data were analyzed using a two-way analysis of variance
      (P < 0.05). Failure modes were descriptively interpreted. RESULTS: Cyclic testing
      data revealed no difference between constructs at any interval. Within all
      construct groups, displacement that occurred did so within the first 500 cycles
      of testing. Pre- and postcyclic loading radiographic analysis showed no
      differences in construct deformation. Load to failure testing revealed no
      differences between groups, whereas volar constructs approached significance (P =
      0.08) for increased failure strength. Dorsal constructs failed primarily by
      fragment subsidence and fragmentation, whereas volar constructs failed by plate
      bending. CONCLUSIONS: No difference in all measured biomechanical parameters
      supports equivalence between constructs and surgeon discretion in determining
      operative method. Minimal fragment displacement and construct deformation during
      physiological testing support previous data that early postoperative motion can
      be recommended. Fragment displacement that occurs does so in the early periods of
      motion.

PMID- 21085030
TI  - A prospective clinical study of proximal humerus fractures treated with a locking
      proximal humerus plate.
AB  - OBJECTIVES: The purpose of this prospective study was to evaluate the safety,
      efficacy, and functional outcome of the locked proximal humerus plate (LPHP) to
      treat proximal humerus fractures. DESIGN: Prospective clinical trial. SETTING:
      University orthopedic center. PATIENTS: Over a 25-month period, 64 consecutive
      patients were treated with a LPHP for an unstable or displaced proximal humerus
      fracture. INTERVENTION: Demographic data, trauma mechanisms, surgical approaches,
      and postoperative complications were collected from medical records. Fracture
      classification according to the Neer classification, radiographic head-shaft
      angle, and screw tip-articular surface distance in true anteroposterior and
      axillary lateral radiographs of the shoulder were measured postoperatively. MAIN
      OUTCOME MEASUREMENTS: The functional outcome was evaluated with a Constant-Murley
      (CM) evaluation. The CM score is a validated shoulder-specific scoring system in
      which patients report subjective findings. The physician reported the objective
      measurements of the shoulder. RESULTS: Follow-ups were completed for all of the
      patients. The overall complication rate was 35.9%, with screw penetration into
      the glenohumeral joint as the most frequent problem (7.6%). Deep wound infections
      were observed in 3.1% (n = 2) of the cases and avascular necrosis in 3.1% (n =
      2). All complications occurred in 4-part fractures. Subacromial impingement,
      frozen shoulder, rotator cuff rupture, and wound dehiscence were observed in 3.1%
      (n = 2), 3.1% (n = 2), 1.6% (n = 1), and 1.6% (n = 1) of the cases, respectively.
      Multivariate linear regression analysis revealed that the fracture pattern and
      the presence or absence of medial support were significant predictors of
      functional outcome (P = 0.026 and P = 0.003, respectively). Patient age (P =
      0.581), sex (P = 0.325), and initial tuberosity displacement (varus/extension or
      valgus/impaction; P = 0.059) were not significantly associated with the CM score.
      CONCLUSIONS: The LPHP seems to be a promising implant for the fixation of
      proximal humerus fractures. However, there are certain limitations that should be
      mentioned. The number of cases in our study was small, and no safe conclusions
      can be extracted regarding the rate of avascular necrosis. Additional studies
      with larger cohorts and longer follow-ups are necessary to better define the
      appropriate indications for and expected outcomes of this technology.

PMID- 21085031
TI  - Influence of preferred versus prescribed exercise on pain in fibromyalgia.
AB  - PURPOSE: The purpose of this study was to examine the influence of a preferred-
      versus a prescribed-intensity exercise session on pain in women with fibromyalgia
      (FM). METHODS: Twenty-one women with FM (mean age = 44 yr) completed two randomly
      assigned exercise sessions consisting of 20 min of cycle ergometry at a self
      selected intensity and a prescribed intensity. Experimental pain perception was
      assessed before and after aerobic exercise. During exercise, HR, watts, RPE, and
      muscle pain were assessed every 5 min. Clinical pain was assessed with the Short
      Form McGill Pain Questionnaire (SF-MPQ) immediately and 24, 48, 72, and 96 h
      after exercise. Data were analyzed with repeated-measures ANOVA. RESULTS: Women
      with FM preferred a lower intensity of exercise than what was prescribed as
      indicated by significantly lower HR, watts, and RPE responses (P < 0.05). Muscle
      pain in the legs, however, was similar in the two conditions and significantly
      increased during exercise (P < 0.05). Pain thresholds and pain tolerances
      increased significantly after exercise, whereas peak pain ratings decreased after
      exercise (P < 0.05). Furthermore, pain (SF-MPQ) in the follow-up period was found
      to be lower than baseline (P < 0.05). CONCLUSIONS: It is concluded that the women
      with FM who participated in this study experienced significant improvements in
      pain after exercise. The results from this study are novel and indicate that
      recommendations for exercise prescription for individuals with FM should consider
      the preferred-intensity exercise model as a strategy to reduce pain.

PMID- 21085032
TI  - Venous and arterial bubbles at rest after no-decompression air dives.
AB  - PURPOSE: During SCUBA diving, breathing at increased pressure leads to a greater
      tissue gas uptake. During ascent, tissues may become supersaturated, and the gas
      is released in the form of bubbles that typically occur on the venous side of
      circulation. These venous gas emboli (VGE) are usually eliminated as they pass
      through the lungs, although their occasional presence in systemic circulation
      (arterialization) has been reported and it was assumed to be the main cause of
      the decompression sickness. The aims of the present study were to assess the
      appearance of VGE after air dives where no stops in coming to the surface are
      required and to assess their potential occurrence and frequency in the systemic
      circulation. METHODS: Twelve male divers performed six dives with 3 d of rest
      between them following standard no-decompression dive procedures: 18/60, 18/70,
      24/30, 24/40, 33/15, and 33/20 (the first value indicates depth in meters of sea
      water and the second value indicates bottom time in minutes). VGE monitoring was
      performed ultrasonographically every 20 min for 120 min after surfacing. RESULTS:
      Diving profiles used in this study produced unexpectedly high amounts of gas
      bubbles, with most dives resulting in grade 4 (55/69 dives) on the bubble scale
      of 0-5 (no to maximal bubbles). Arterializations of gas bubbles were found in 5
      (41.7%) of 12 divers and after 11 (16%) of 69 dives. These VGE crossovers were
      only observed when a large amount of bubbles was concomitantly present in the
      right valve of the heart. CONCLUSIONS: Our findings indicate high amounts of gas
      bubbles produced after no-decompression air dives based on standardized diving
      protocols. High bubble loads were frequently associated with the crossover of VGE
      to the systemic circulation. Despite these findings, no acute decompression
      related pathology was detected.

PMID- 21085033
TI  - Disproportionate exercise load and remodeling of the athlete's right ventricle.
AB  - PURPOSE: There is evolving evidence that intense exercise may place a
      disproportionate load on the right ventricle (RV) when compared with the left
      ventricle (LV) of the heart. Using a novel method of estimating end-systolic wall
      stress (ES-sigma), we compared the RV and LV during exercise and assessed whether
      this influenced chronic ventricular remodeling in athletes. METHODS: For this
      study, 39 endurance athletes (EA) and 14 nonathletes (NA) underwent resting
      cardiac magnetic resonance (CMR), maximal oxygen uptake (VO2), and exercise
      echocardiography studies. LV and RV end-systolic wall stress (ES-sigma) were
      calculated using the Laplace relation (ES-sigma = Pr/(2h)). Ventricular size and
      wall thickness were determined by CMR; invasive and Doppler echo estimates were
      used to measure systemic and pulmonary ventricular pressures, respectively; and
      stroke volume was quantified by Doppler echocardiography and used to calculate
      changes in ventricular geometry during exercise. RESULTS: In EA, compared with
      NA, resting CMR measures showed greater RV than LV remodeling. The ratios RV
      ESV/LV ESV (1.40 +/- 0.23 vs 1.26 +/- 0.12, P = 0.007) and RV mass/LV mass (0.29
      +/- 0.04 vs 0.25 +/- 0.03, P = 0.012) were greater in EA than in NA. RVES-sigma
      was lower at rest than LVES-sigma (143 +/- 44 vs 252 +/- 49 kdyn . cm, P < 0.001)
      but increased more with strenuous exercise (125% vs 14%, P < 0.001), resulting in
      similar peak exercise ES-sigma (321 +/- 106 vs 286 +/- 77 kdyn . cm, P = 0.058).
      Peak exercise RVES-sigma was greater in EA than in NA (340 +/- 107 vs 266 +/- 82
      kdyn . cm, P = 0.028), whereas RVES-sigma at matched absolute workloads did not
      differ (P = 0.79). CONCLUSIONS: Exercise induces a relative increase in RVES
      sigma which exceeds LVES-sigma. In athletes, greater RV enlargement and greater
      wall thickening may be a product of this disproportionate load excess.

PMID- 21085034
TI  - Validation of a talking pedometer for adults with visual impairment.
AB  - Alterations in gait mechanics and mobility aid (MA) use have been observed in
      persons with visual impairment (VI) in response to environmental changes, yet the
      influence of these modifications on the accuracy of an adaptive pedometer has not
      been documented. PURPOSE: The purpose of this study was to establish validity
      evidence for the Centrios talking pedometer relative to environmental familiarity
      and MA use in adults with VI. METHODS: Thirteen adults with VI (age = 38 +/- 14
      yr) completed two walking trials over an unfamiliar, quarter-mile course while
      wearing a Centrios talking pedometer at the right and left sides of the hip.
      Walking speed, pedometer-determined steps, and actual steps were recorded during
      the first session, reflecting walking in an "unfamiliar environment." After a
      series of additional walks over the same course, outcome measures were reassessed
      during a second trial, reflecting walking in a "familiar environment." Absolute
      percent error (APE) scores were calculated between actual and pedometer
      determined steps. Paired t-tests were used to assess differences in APE relative
      to mounting position across environmental settings. RESULTS: During unfamiliar
      trials, the pedometer accurately reported steps when mounted at the hip opposite
      the user's MA (APE = 2.1%) but was significantly less accurate when mounted at
      the hip on the user's MA side (APE = 11.1%). In the familiar setting, the
      pedometer accurately reported steps when mounted at the left hip and the hip
      opposite the user's MA (APE <3%). APE values did not differ across environmental
      conditions (P > 0.05). CONCLUSIONS: In unfamiliar and familiar walking
      conditions, the Centrios pedometer accurately monitors step-based activity in
      adults with VI when mounted at the hip opposite the user's MA.

PMID- 21085035
TI  - Similar dynamic hyperinflation during arm and leg exercise at similar ventilation
      in chronic obstructive pulmonary disease.
AB  - PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) report more
      dyspnea during arm than during leg exercise. One of the major causes of dyspnea
      is dynamic hyperinflation (DH), which is caused by airflow limitation as well as
      increase in ventilation. The aims of our study were to compare DH at equal
      ventilation (isoventilation) during arm and legwork and to investigate the
      effects of breathing pattern on DH. METHODS: Thirteen clinically stable patients
      with mild to very severe COPD (forced expiratory volume in 1 s = 59% +/- 21%)
      participated in this study. Arm and leg constant work rate (CWR) ergometry were
      performed in random order with ventilation equal to that at 50% of peak armload.
      The corresponding leg load of that level of ventilation was determined from the
      incremental leg test. Respiratory physiology was measured breath-by-breath.
      Change in inspiratory capacity, measured at rest and at 2-min intervals, was used
      to reflect DH. RESULTS: At steady-state isoventilation (37 +/- 2 and 36 +/- 2 L .
      min for arm and leg CWR tests, respectively, P > 0.05), armload was 29 +/- 5 W
      and leg load was 52 +/- 6 W (P < 0.001). The level of DH, 0.32 +/- 0.09 and 0.27
      +/- 0.08 L during arm and leg exercises, respectively, was not significantly
      different. However, breathing frequency was greater during arm than during leg
      exercise (24 +/- 1 vs 21 +/- 1 breaths per minute, P < 0.01), and the opposite
      was true for tidal volume (1.56 +/- 0.15 vs 1.69 +/- 0.14 L, P < 0.01).
      CONCLUSIONS: At similar ventilation, we found a similar degree of DH during arm
      and leg CWR tests in patients with mild to very severe COPD. Although differences
      in breathing pattern were observed between arm and leg exercises, these did not
      affect the level of DH.

PMID- 21085036
TI  - Sixteen weeks of exercise reduces C-reactive protein levels in young women.
AB  - PURPOSE: Regular exercise has been shown to protect against breast cancer risk,
      and one possible mechanism is through a reduction in inflammation. The purpose of
      this study was to examine the effects of 16 wk of aerobic exercise training on
      adipokines and inflammatory markers in healthy young women. METHODS: Participants
      were 319 sedentary women aged 18-30 yr, with body mass index of 18-40 kg . m,
      randomized to an exercise intervention or no exercise for approximately 16 wk.
      Adiponectin, leptin, C-reactive protein (CRP), and amyloid A (AA) were measured
      at baseline and after 16 wk. Adiponectin was measured by enzyme-linked
      immunosorbent assay, and AA, CRP, and leptin were measured by multiplex bead
      array assays. RESULTS: Exercise significantly decreased CRP levels in the
      exercise group compared with the control group (-1.41 mg . L in exercisers vs 
      0.005 mg . L in controls, P = 0.040), and this effect was largely driven by
      changes in CRP that occurred in the obese exercisers. There was no effect of
      exercise on levels of SAA, adiponectin, or leptin. There was also no effect of
      exercise on stress and depression scores. Neither change in percent body fat nor
      change in fitness influenced the effects of exercise on these inflammatory
      markers. CONCLUSIONS: This study demonstrated that a 16-wk aerobic exercise
      program significantly decreased levels of CRP in young women, especially in those
      who were obese. There was no evidence that this effect was mediated by changes in
      perceived stress, percent body fat, or fitness. These findings suggest that
      adopting an exercise routine early in life may decrease future risk of breast
      cancer and other chronic diseases in obese women.

PMID- 21085037
TI  - Accuracy of physical activity monitors in pregnant women.
AB  - PURPOSE: To determine the step count accuracy of three pedometers and one
      accelerometer in pregnant women during treadmill walking. METHODS: Participants
      were 30 women in the second or third trimester (20-34 wk) who were screened for
      pregnancy-related risk factors. Each participant was fitted with a belt
      containing three physical activity monitors: Yamax Digiwalker SW-200 (DW), New
      Lifestyles NL 2000 (NL), and GT3X ActiGraph accelerometer (ACT). The Omron HJ
      720ITC (HJ) was placed in the pants' front pocket. Participants walked at 54, 67,
      80, and 94 m . min for 2 min each. Actual steps were determined by an
      investigator using a hand-tally counter. The mean percent of steps recorded was
      calculated for each device at each speed and compared. Pearson correlations were
      used to determine the effect of body mass index and tilt angle on pedometer
      accuracy. RESULTS: There was a significant interaction between speed and device
      (F9,20 = 7.574, P < 0.001). Across all speeds, the NL and HJ had the lowest
      error. The ACT and DW underestimated the actual steps taken, particularly at the
      slower walking speeds. At 54 m . min, the ACT averaged 77.5% of steps and the DW
      averaged 56.9% of steps. Significant differences in the mean percent of steps
      recorded were found between devices at all speeds. Body mass index was only
      significantly correlated with percent of steps recorded by the NL, and there were
      no significant correlations between steps recorded and tilt angle. CONCLUSIONS:
      In pregnant women, the ACT and DW had more error than the NL and HJ. On the basis
      of these results, the NL and HJ should be considered for use in further research
      studies and physical activity programs that focus on walking during pregnancy.

PMID- 21085038
TI  - Postpartum exercise regardless of intensity improves chronic disease risk
      factors.
AB  - PURPOSE: Women who are unable to return to a healthy weight by 6 months
      postpartum increase their risk factors for the development of chronic disease
      (CD; including metabolic syndrome, obesity, and cardiovascular disease). In a
      prospective randomized intervention study, we examined the effect of exercise
      intensity on risk factors for CD in the postpartum. We hypothesized that women
      receiving an intervention targeting healthy weight loss would have improved CD
      risk factors compared with women not receiving the intervention. Further, we
      hypothesized that nutrition control and moderate-intensity exercise would have
      the greatest improvement in CD risk factors versus low-intensity exercise.
      METHODS: Women were randomly assigned to a nutrition plus low-intensity (30% HR
      reserve; n = 20) or moderate-intensity (70% HR reserve; n = 20) exercise
      intervention group. The program consisted of supervised walking for 45 min, three
      to four times per week for 16 wk. All women were screened for CD at the beginning
      (7-8 wk postpartum) and at the end (23-25 wk postpartum) of the study. A
      historical control group of 20 sedentary postpartum women was matched by body
      mass index, age, and parity. RESULTS: The low- and moderate-intensity groups lost
      more body mass (-4.2 +/- 4.0 and -5.0 +/- 2.9 kg, respectively) compared with the
      control group (-0.1 +/- 3.3 kg, P < 0.01). Plasma low-density lipoprotein was
      reduced for the low- and moderate-intensity groups (-0.29 +/- 0.21 and -0.28 +/-
      0.17 mmol . L) compared with the control group (0.03 +/- 0.18 mmol . L, P =
      0.015). In addition, glucose concentrations were reduced and adiponectin
      concentrations increased (P = 0.037), regardless of exercise intensity, although
      the sedentary controls remained unchanged or at increased risk for CD.
      CONCLUSIONS: Women receiving a postpartum intervention targeting healthy weight
      loss, regardless of exercise intensity, improved CD risk factors compared with
      women not receiving the intervention.

PMID- 21085039
TI  - Modeling the association between HR variability and illness in elite swimmers.
AB  - PURPOSE: To determine whether HR variability (HRV), an indirect measure of
      autonomic control, is associated with upper respiratory tract and pulmonary
      infections, muscular affections, and all-type pathologies in elite swimmers.
      METHODS: For this study, 7 elite international and 11 national swimmers were
      observed weekly for 2 yr. The indexes of cardiac autonomic regulation in supine
      and orthostatic position were assessed as explanatory variables by time domain
      (SD1, SD2) and spectral analyses (high frequency [HF] = 0.15-0.40 Hz, low
      frequency [LF] = 0.04-0.15 Hz, and HF/LF ratio) of HRV. Logistic mixed models
      described the relationship between the explanatory variables and the risk of
      upper respiratory tract and pulmonary infections, muscular affections, and all
      type pathologies. RESULTS: The risk of all-type pathologies was higher for
      national swimmers and in winter (P < 0.01). An increase in the parasympathetic
      indexes (HF, SD1) in the supine position assessed 1 wk earlier was linked to a
      higher risk of upper respiratory tract and pulmonary infections (P < 0.05) and to
      a higher risk of muscular affections (increase in HF, P < 0.05). Multivariate
      analyses showed (1) a higher all-type pathologies risk in winter and for an
      increase in the total power of HRV associated with a decline SD1 in supine
      position, (2) a higher all-type pathologies risk in winter associated with a
      decline in HF assessed 1 wk earlier in orthostatic position, and (3) a higher
      risk of muscular affections in winter associated with a decrease SD1 and an
      increase LF in orthostatic position. CONCLUSIONS: Swimmers' health maintenance
      requires particular attention when autonomic balance shows a sudden increase in
      parasympathetic indices in the supine position assessed 1 wk earlier evolving
      toward sympathetic predominance in supine and orthostatic positions.

PMID- 21085040
TI  - Implications of exercise-induced pulmonary arterial hypertension.
AB  - PURPOSE: To characterize the hemodynamic and ventilatory responses to exercise in
      a group of patients with unexplained dyspnea, increased risk for pulmonary
      arterial hypertension (PAH), and an elevated mean pulmonary artery pressure
      (mPAP; >30 mm Hg) on exercise. METHODS: A total of 37 symptomatic patients at
      risk of PAH and 20 healthy controls underwent a cardiopulmonary exercise test and
      were assessed for quality of life (QOL). Patients had a pulmonary artery catheter
      in situ during the exercise test. RESULTS: Seventeen subjects had exercise
      induced PAH (EIPAH), which we defined as mPAP <= 25 mm Hg at rest, and mPAP > 30
      mm Hg and pulmonary artery wedge pressure <20 mm Hg on exercise. These subjects
      had reduced peak exercise cardiac output (72% +/- 19% predicted). Further,
      compared with matched controls, subjects with EIPAH had reduced peak oxygen
      consumption (1.2 +/- 0.4 vs 1.7 +/- 0.5 L . min, P < 0.05), an elevated
      ventilatory equivalent for carbon dioxide (41.0 +/- 7.3 vs 31.0 +/- 2.9, P <
      0.05) and reduced end-tidal carbon dioxide tension (32.6 +/- 3.6 vs 39.4 +/- 2.7
      mm Hg, P < 0.05) at the anaerobic threshold. These exercise abnormalities were
      associated with impaired QOL (P < 0.05). CONCLUSIONS: Elevated pulmonary artery
      pressure on exercise can be associated with hemodynamic and ventilatory
      abnormalities typical of PAH, along with impaired exercise capacity and reduced
      QOL.

PMID- 21085041
TI  - Neuromuscular recovery after medial collateral ligament disruption and eccentric
      rehabilitation program.
AB  - PURPOSE: Medial collateral ligament (MCL) rupture of the knee joint frequently
      occurs during sport activities. However, the optimal rehabilitation strategy
      after such lesion is unknown. The aim of this study was to assess the effects of
      progressive eccentric rehabilitation program on neuromuscular deficits induced by
      MCL transection. METHODS: Rats were randomized as follows: (i) control group (C,
      n = 10) without any surgery; (ii) lesion groups in which neuromuscular
      measurements were made 1 (L1, n = 10) and 3 wk (L3, n = 9) after MCL transection
      by a 15- to 20-min surgery (this group was designed to determine changes induced
      by the MCL transection); and (iii) eccentric group (ECC, n = 7) in which rats
      performed a progressive 2-wk eccentric rehabilitation program beginning 1 wk
      after MCL transection surgery. Dynamic functional assessments were performed at
      weeks 1 and 3 after the MCL transection by measuring the maximal and minimal knee
      angles during the stance phase of the gait cycle. Neuromuscular measurements
      included 1) modulation of H-reflex in response to a 10-mM KCl injection, 2)
      analysis of the twitch relaxation properties of the quadriceps muscle, and 3)
      recording of metabosensitive and mechanosensitive afferents activity in response
      to chemical injections and to tendon patellar vibrations, respectively. RESULTS:
      Our results indicated that H-reflex modulation induced by metabosensitive
      afferents was disturbed by MCL transection without any recovery despite
      rehabilitation program. Responses of both metabosensitive and mechanosensitive
      muscle afferents, as well as the muscle relaxation properties, were fully
      recovered after the eccentric rehabilitation program. CONCLUSIONS: Our results
      directly indicated an influence of progressive eccentric program on muscle
      afferents response after MCL section but apparently not for spinal reflex
      modulation.

PMID- 21085042
TI  - Cardiovascular risk and clinical factors in athletes: 10 years of evaluation.
AB  - PURPOSE: Preparticipation screening in athletes is a very current but
      controversial theme. Part of this controversy is due to the cost benefit,
      especially when the screening is merely used as a prevention of sudden cardiac
      death caused by rare and hereditary diseases. The purpose of this study was to
      describe the prevalence of preexisting diseases, cardiovascular risk factor for
      cardiovascular diseases development, and hematological profile in a population of
      amateur and professional athletes. METHODS: Data of 623 athletes (529 men and 94
      women), aged 13-77 yr, were analyzed to detect preexisting diseases. The
      variables total cholesterol, LDL, HDL, triglycerides, fasting glucose, body mass
      index, hemoglobin, hematocrit, and ferritin were analyzed in two groups according
      to age, that is, younger and older 35 yr old, and their prevalence (%) and
      distribution in quartiles were presented. chi test and Pearson product-moment
      correlation coefficients between variables were applied, and P < 0.05 was adopted
      for significance. RESULTS: Hypertension was the most prevalent preexisting
      diseases, although the data showed low prevalence of cardiomyopathy.
      Cardiovascular risk factors were prevalent in both genders. There were positive
      correlations between cardiovascular risk factors and age and between body mass
      index and lipid levels in male athletes. Also, there was a high prevalence of low
      ferritin levels for women, with positive correlation between the levels of
      hemoglobin and ferritin. CONCLUSIONS: In the present study, hypertension was the
      most prevalent diagnosed disease, and cardiovascular risk factors showed
      important prevalence, especially in athletes older than 35 yr. Although physical
      training represents a cardioprotective factor to the onset of cardiovascular
      disease, it does not exclude the prevalence of risk factors and diseases in
      athletes.

PMID- 21085043
TI  - Antioxidant supplementation reduces skeletal muscle mitochondrial biogenesis.
AB  - PURPOSE: Exercise increases the production of reactive oxygen species (ROS) in
      skeletal muscle, and athletes often consume antioxidant supplements in the belief
      they will attenuate ROS-related muscle damage and fatigue during exercise.
      However, exercise-induced ROS may regulate beneficial skeletal muscle
      adaptations, such as increased mitochondrial biogenesis. We therefore
      investigated the effects of long-term antioxidant supplementation with vitamin E
      and alpha-lipoic acid on changes in markers of mitochondrial biogenesis in the
      skeletal muscle of exercise-trained and sedentary rats. METHODS: Male Wistar rats
      were divided into four groups: 1) sedentary control diet, 2) sedentary
      antioxidant diet, 3) exercise control diet, and 4) exercise antioxidant diet.
      Animals ran on a treadmill 4 d . wk at ~ 70%VO2max for up to 90 min . d for 14
      wk. RESULTS: Consistent with the augmentation of skeletal muscle mitochondrial
      biogenesis and antioxidant defenses, after training there were significant
      increases in peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PGC-1alpha) messenger RNA (mRNA) and protein, cytochrome C oxidase subunit IV
      (COX IV) and cytochrome C protein abundance, citrate synthase activity, Nfe2l2,
      and SOD2 protein (P < 0.05). Antioxidant supplementation reduced PGC-1alpha mRNA,
      PGC-1alpha and COX IV protein, and citrate synthase enzyme activity (P < 0.05) in
      both sedentary and exercise-trained rats. CONCLUSIONS: Vitamin E and alpha-lipoic
      acid supplementation suppresses skeletal muscle mitochondrial biogenesis,
      regardless of training status.

PMID- 21085044
TI  - Differences in the kinematics of the baseball swing between hitters of varying
      skill.
AB  - PURPOSE: The aim of this study was to determine differences in bat swing
      kinematics in baseball hitters of varying ability. METHODS: Kinematic data for
      the upper and lower body were collected from 20 trained male baseball players
      (22.3 +/- 5.3 yr, 1.82 +/- 0.07 m, 83.5 +/- 10.9 kg), using three-dimensional
      computerized motion-analysis techniques. Participants were ranked before testing
      based on a novel coach's rating scale and seasonal batting average. They were
      subsequently separated into a relatively high-caliber group of hitters (n = 10)
      and a relatively low-caliber group of hitters (n = 10) for comparison.
      Importantly, the two groups were significantly different in terms of coach's
      rating (P < 0.01) and batting average (P < 0.05). RESULTS: The results showed a
      significant difference in maximum bat swing velocity (P < 0.05) with high-caliber
      hitters having a higher velocity (36.8 m . s) in comparison with relatively low
      caliber hitters (33.8 m . s). Lead elbow maximum angular velocity was
      significantly higher (35.9%) among relatively high-caliber hitters (P < 0.05).
      Angular velocity of the hip segment approached significance between the groups (P
      = 0.056). High-caliber hitters also had a right knee angle of 106 degrees  at
      ball contact, which was significantly (P < 0.05) higher than that of relatively
      low-caliber hitters (100 degrees ). There were no between-group differences for
      wrist and linear hip joint velocities at ball contact. CONCLUSIONS: It was
      established that bat swing velocity is a key characteristic of the baseball swing
      when identifying skill level and performance between hitters. In addition, high
      caliber hitters display greater lead elbow maximum angular velocity possibly
      because of achieving a higher angular hip segment velocity early in the swing. It
      is noted that although these attributes differentiate hitters of varying skill
      level, future research should examine whether developing these characteristics in
      players of lower ability improves batting performance.

PMID- 21085045
TI  - Significance of increased scrotal Tc-99m MDP uptake in patients with prostate
      cancer.
AB  - OBJECTIVE: We observed an unusually increased scrotal uptake as an interesting
      finding in some patients with prostate cancer who were scanned for any possible
      metastatic disease. This study was designed to investigate the significance of
      this incidental finding in the technetium-99m methylene diphosphonate
      scintigraphies. METHODS: The study population consisted of 104 patients with
      biopsy-proven prostate cancer (group I), 55 male patients with other cancers
      (group II), 30 male patients with nonmalignant diseases (group III) and finally
      15 patients with benign prostate hypertrophy (group IV). The square-shaped
      regions of interest are placed centrally on the scrotum and then on the lateral
      femoral soft tissue. Then the simple ratios of the scrotal and femoral soft
      tissue mean counts (S/Bg) were calculated. The statistical significance of
      differences among the groups in terms of scrotal uptake was determined. RESULTS:
      Group I showed increased scrotal uptake relative to the other groups. The mean
      uptake ratios (S/Bg+/-standard deviation) were 3.49+/-1.42 in group I, 2.89+/
      0.70 in group II, 2.87+/-0.75 in group III, and 2.91+/-0.60 in group IV. This
      ratio was significantly higher in patients with prostate cancer than the normal
      group (P=0.024), the group with benign prostate hypertrophy (P=0.004), and the
      patients with other cancers (P=0.004). CONCLUSION: Our results showed that
      technetium-99m methylene diphosphonate bone scintigraphy, as a routine for
      detecting metastatic disease or performed for other purposes, could give clues
      for a hidden prostate cancer. Then, in elderly male patients, we strongly
      recommend that it is wise to keep one's eye on scrotal activity when bone scans
      are read and where there is any doubt, take appropriate regions of interest to
      make quantitative evaluations.

PMID- 21085046
TI  - The role of fluorodeoxyglucose-positron emission tomography/computed tomography
      in differentiating between benign and malignant adrenal lesions.
AB  - OBJECTIVES: This retrospective study was designed to investigate the clinical
      role of whole-body positron emission tomography/computed tomography (PET/CT) by
      using 2-[18F]fluoro-2-deoxy-D-glucose (FDG), for the evaluation of adrenal
      lesions and to find the best index to distinguish benign from malignant lesions
      in various cancer patients. MATERIALS AND METHODS: A total of 81 patients (55
      male and 26 female, age range: 31-81 years, mean: 61.5) who had confirmed primary
      malignancies (lung cancer in 47 patients, gastrointestinal malignancies in 13
      patients, malignant melanoma in one patient, renal cell cancer in three patients,
      mesothelioma in two patients, breast carcinoma in nine patients, cervical cancer
      in one patient, ovarian cancer in two patients, pheochromocytoma in one patient,
      unknown primary in two patients) underwent PET/CT examinations for cancer
      screening, staging, restaging, and detection of suspected recurrence. Of the 81
      patients, 104 adrenal lesions (34 benign and 70 malignant adrenal lesions) were
      shown by CT. On visual analysis of PET/CT imaging, adrenal uptake was based on a
      three-scale grading system. For final assessment standards of references for
      adrenal malignant lesions was based on biopsy (n=2), interval growth, or
      reduction after chemotherapy. An adrenal lesion, which remained unchanged on
      clinical and imaging follow-up of at least 7 months (mean follow-up time 19.31
      months+/-6.46, range 7-30 months), was decided as a benign lesion. RESULTS: In
      adrenal malignant lesions maximum standardized uptake value (SUVmax) (8.82+/
      4.47) was higher than that of adrenal benign lesions (3.02+/-1.15, P<0.0001). In
      the differentiation of adrenal benign and malignant lesions, a CT threshold of 10
      Hounsfield units corresponded to a sensitivity of 64.7%, specificity of 98.6%,
      and accuracy of 87.5%. An SUVmax cut-off value of 2.5 corresponded to a
      sensitivity of 100%, specificity of 38.2%, and accuracy of 80%. An SUVmax cut-off
      value of 4.2 corresponded to a sensitivity of 88.6%, specificity of 88.2%, and
      accuracy of 88.5%. The ratio of tumor SUVmax to liver SUVmean was 3.61+/-1.77 for
      adrenal malignant lesions whereas it was 1.20+/-0.38 for adrenal benign lesions
      (P<0.0001). T/L SUV ratio cut-off value of 1.8 corresponded to a sensitivity of
      87%, specificity of 91%, and accuracy of 88.5%. T/L SUV ratio cut-off value of
      1.68 corresponded to a sensitivity of 90%, specificity of 91.1%, and accuracy of
      90.4%. CONCLUSION: 2-[18F]fluoro-2-deoxy-D-glucose-PET/CT improves the diagnostic
      accuracy in the differentiation of benign from malignant adrenal lesions in
      various cancer patients. Combined information obtained from PET/CT (SUVmax, T/L
      SUV ratio, visual analysis) and unenhanced CT (size, Hounsfield units
      measurement) is recommended for better differentiation.

PMID- 21085047
TI  - Evaluation of [18F]-tetrafluoroborate as a potential PET imaging agent for the
      human sodium/iodide symporter in a new colon carcinoma cell line, HCT116,
      expressing hNIS.
AB  - PURPOSE: Accumulation of iodide and other substrates via the human sodium/iodide
      symporter (hNIS) is fundamental to imaging and therapy of thyroid disease, hNIS
      reporter gene imaging and hNIS-mediated gene therapy. There is no readily
      available positron emission tomography (PET) tracer for hNIS. Our aim was to
      develop a colon carcinoma cell line stably expressing hNIS, and use it to
      evaluate a novel hNIS PET tracer, [18F]-tetrafluoroborate. METHODS: Colon
      carcinoma cell line, HCT116, was stably transfected with hNIS, thus producing a
      cell line, HCT116-C19, with high hNIS expression. A Fisher rat thyroid cell line,
      FRTL5, which expresses rat sodium/iodide symporter when stimulated with thyroid
      stimulating hormone, was used for comparison. Accumulation of [188Re]-perrhenate,
      [99mTc]-pertechnetate and [18F]-tetrafluoroborate was evaluated with and without
      perchlorate inhibition using an automated radioimmune assay system, LigandTracer.
      The affinity of [18F]-tetrafluoroborate for hNIS, and its half-maximal inhibitory
      concentration (IC50) for the inhibition of [99mTc]-pertechnetate transport were
      determined from the plateau accumulation of [18F]-tetrafluoroborate and [99mTc]
      pertechnetate, respectively, as a function of tetrafluoroborate concentration.
      RESULTS: [18F]-tetrafluoroborate accumulated effectively in both FRTL5 and HCT116
      C19 cells. The accumulation in HCT116-C19 cells (plateau accumulation 31%) was
      comparable to that of [188Re]-perrhenate (41%) and [99mTc]-pertechnetate (46%).
      Its affinity for hNIS and half-maximal inhibitory concentration (IC50) for the
      inhibition of pertechnetate uptake was approximately micromolar. CONCLUSION: We
      have produced a human colon cell line with a stable constitutive expression of
      functional hNIS (HCT116-hNIS-C19). [18F]-tetrafluoroborate accumulates in cells
      expressing hNIS or rat sodium/iodide symporter and is a potential PET imaging
      agent in thyroid disease and hNIS reporter gene imaging.

PMID- 21085048
TI  - Fluconazole loading dose pharmacokinetics and safety in infants.
AB  - BACKGROUND: Invasive candidiasis is a leading cause of morbidity and mortality in
      critically ill infants. Prompt administration of fluconazole and achievement of
      the therapeutic target (area under the curve 0 to 24 hours >400 mg*h/L) improve
      outcomes in candidemic patients. A loading dose of fluconazole is advised for
      older patients but has not been evaluated in infants. We sought to determine the
      pharmacokinetics and safety of a fluconazole loading dose in infants at risk for
      invasive fungal infection. METHODS: We enrolled 10 hospitalized infants <60 days
      old with suspected systemic fungal infection in this open-label study; 9 received
      a 25-mg/kg fluconazole loading dose followed by a maintenance dose of 12 mg/kg
      every 24 hours for 4 additional days. Plasma samples were obtained following the
      loading and steady-state doses (doses 3-5). We used a 1-compartment model to fit
      the data to estimate pharmacokinetic indices. RESULTS: Data from 57 drug
      concentrations obtained from 8 infants (median postnatal age, 16 days
      [interquartile range, 13-32] and median gestational age, 37 weeks [35-38]) showed
      that the median fluconazole area under the curve 0 to 24 hours (mg*h/L) in this
      population was 479 (347-496). Of the 8 infants who received the loading dose, 5
      (63%) achieved the therapeutic target on the first day of dosing, and all infants
      achieved a fluconazole 24-hour trough concentration >8 MUg/mL. No adverse events
      were thought to be related to fluconazole therapy. CONCLUSIONS: A loading dose of
      fluconazole (25 mg/kg) was safe in this small cohort of young infants and
      achieved the therapeutic target more rapidly than traditional dosing.

PMID- 21085049
TI  - Carried pneumococci in Massachusetts children: the contribution of clonal
      expansion and serotype switching.
AB  - BACKGROUND: Vaccination against 7 serotypes of Streptococcus pneumoniae has led
      to the near extinction of vaccine serotypes in both disease and asymptomatic
      carriage. In carriage, vaccine serotypes have been replaced by nonvaccine
      serotypes. METHODS: We used multilocus sequence typing to analyze a sample of 294
      isolates of S. pneumoniae carried by Massachusetts children (aged, 3 months-7
      years) and examine the results for serotype switching and association with
      antimicrobial resistance. RESULTS: Eighty-six distinct sequence types (STs) were
      found, 10 of which exhibited a serotype other than that which would be expected
      from previous carriage samples. We interpret this as evidence of past or recent
      serotype switching. Switched variants include ST 320, which is a common and
      increasing source of multidrug resistance in this community. Switching events
      within serogroups were more common than expected by chance (P = 0.043 by a Monte
      Carlo approach). Using multilocus sequence typing data and eBURST analysis, we
      also describe clonal dynamics within the important replacement serotypes 19A,
      15B/C, 35B, and the recently described 6C. CONCLUSIONS: Some strains generated by
      serotype switching are increasingly important parts of the carriage population.
      In the case of 19A, it appears that the majority of increase is due to ST 320, a
      recently reported switched variant. This may have consequences for the STs
      causing invasive pneumococcal disease.

PMID- 21085050
TI  - Reduced thymic size but no evidence of impaired thymic function in uninfected
      children born to human immunodeficiency virus-infected mothers.
AB  - BACKGROUND: HIV-exposed, uninfected (HIV-EU) infants present hematologic and
      immunologic abnormalities at birth, and it remains to be clarified whether these
      abnormalities persist beyond infancy, for instance, affecting vaccination
      responses. METHODS: Thymic size and thymic output were evaluated in 20 HIV-EU
      children at 15 months of age and compared with 10 age- and gender-matched
      controls. Regulatory T-cells (Tregs) and immune activation as well as cytokine
      profiles were determined, and the antibody response to Haemophilus influenzae
      Type b (Hib) vaccination was evaluated. RESULTS: Thymic size was significantly
      lower in HIV-EU children (P = 0.011). However, CD4 and CD8 counts did not differ
      between HIV-EU and control children. Likewise, thymic output estimated as CD4
      cells expressing naive (CD45RA+CD62L+CD27+, P = 0.31) or recent thymic naive
      (CD45RA+CD27+CD31+, P = 0.13) phenotype, or CD4 cells containing T-cell receptor
      excision circles (P = 0.47) were comparable. HIV-EU children and controls had
      similar levels of activated cells (CD4+CD38+HLA-DR+, P = 0.87; CD8+CD38+HLA-DR+,
      P = 0.22), Tregs (CD4+CD25+CD127(low)FOXP3+, P = 0.53), and naive Tregs
      (CD4+CD25+CD127(low)FOXP3+CD45RA+CD27+, P = 0.65). Finally, comparable titers of
      Haemophilus influenzae Type b antibodies in the 2 groups were found (P = 0.43).
      CONCLUSION: The study demonstrates reduced thymic size in HIV-EU children
      compared with children born to HIV-negative mothers, but no evidence of impaired
      thymic function, immune regulation, or antibody vaccination response was
      detected, suggesting that no qualitative immune deficits persist in HIV-EU
      children at 15 months of age.

PMID- 21085051
TI  - Effectiveness of a guideline to reduce vancomycin use in the neonatal intensive
      care unit.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommend hospitals
      develop guidelines for the appropriate use of vancomycin as part of comprehensive
      antimicrobial stewardship. The objective of this study was to evaluate the
      effectiveness and safety of a guideline to restrict vancomycin use in the
      neonatal intensive care unit (NICU). METHODS: A vancomycin use guideline was
      introduced in 2 tertiary care NICUs with low incidences of methicillin-resistant
      Staphylococcus aureus infections. We compared all infants >72 hours of age who
      were evaluated for late-onset infection before and after implementation of this
      guideline. RESULTS: Vancomycin start rates were reduced from 6.9 to 4.5 per 1000
      patient-days (35% reduction; P = 0.01) at Brigham and Women's Hospital, and from
      17 to 6.4 per 1000 patient-days (62% reduction; P < 0.0001) at Massachusetts
      General Hospital. The number of infants exposed to vancomycin decreased from 5.2
      to 3.1 per 1000 patient-days (40% reduction; P = 0.008) at Brigham and Women's
      Hospital, and 10.8 to 5.5 per 1000 patient-days (49% reduction; P = 0.009) at
      Massachusetts General Hospital. Causes of infection, duration of bacteremia, and
      incidence of complications or deaths attributable to late-onset infection did not
      change significantly at either institution. CONCLUSIONS: Implementation of a NICU
      vancomycin use guideline significantly reduced exposure of newborns to vancomycin
      without adversely affecting short-term patient safety. Further studies are
      required to evaluate the long-term effect of vancomycin restriction on NICU
      patient safety and microbial ecology, particularly among institutions with higher
      rates of methicillin-resistant Staphylococcus aureus infections.

PMID- 21085052
TI  - Association study of tryptophan hydroxylase 2 gene polymorphisms in bipolar
      disorder patients with panic disorder comorbidity.
AB  - Frequent comorbidity between panic disorder (PD) and mood disorders has been
      widely reported in clinical and epidemiological studies and, recently, an
      increasing attention has been paid to the cooccurrence of PD and bipolar disorder
      (BD). Several studies have shown that an imbalance of serotonin activity could be
      related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible
      candidates for the association with PD. The aim of this study is to investigate a
      possible association between TPH2 gene polymorphisms and the PD comorbidity
      susceptibility.Our sample consisted of 515 patients; 274 patients with BD
      (subtypes I and II), including 45 patients with lifetime panic disorder
      comorbidity and 241 controls. These patients were genotyped for eight tagging
      single nucleotide polymorphisms of the gene of human TPH2. We found significant
      differences between patients with BD, with panic disorder comorbidity, and
      controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359;
      rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731,
      P=0.011; rs4760820, P=0.0259). We also identified significant differences between
      patients with BD, with and without panic disorder comorbidity in the allelic
      analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820,
      P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis
      (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357,
      P=0.052). The haplotype analysis in the group of patients with BD, with and
      without panic disorder comorbidity, was also significant (rs4448731-rs4565946,
      P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further
      studies are needed to replicate the positive association that we observed.

PMID- 21085054
TI  - Family-based association testing of glutamate transporter genes in autism.

PMID- 21085053
TI  - Database of genetic studies of bipolar disorder.
AB  - This study describes the construction and preliminary analysis of a database of
      summary level genetic findings for bipolar disorder from the literature. The
      database is available for noncommercial use at
      http://bioprogramming.bsd.uchicago.edu/BDStudies/. This may be the first complete
      collection of published gene-specific linkage and association findings on bipolar
      disorder, including genome-wide association studies. Both the positive and
      negative findings have been incorporated so that the statistical and contextual
      significance of each finding may be compared semi-quantitatively and
      qualitatively across studies of mixed technologies. The database is appropriate
      for searching a literature populated by mainly underpowered studies, and if
      'hits' are viewed as tentative knowledge for future hypothesis generation. It can
      serve as the basis for a mega-analysis of candidate genes. Herein, we discuss the
      most robust and best replicated gene findings to date in a contextual manner.

PMID- 21085055
TI  - Methylation analysis of the NOTCH4 -25 C/T polymorphism in schizophrenia.
AB  - BACKGROUND: The major histocompatability complex on chromosome 6p has often been
      identified as containing potential risk factors for schizophrenia. The NOTCH4
      gene is located within this region (6p21.3) and sequence variants have previously
      shown association to the disease. It is further implicated from a functional
      standpoint as it plays a critical role during the neurodevelopmental process.
      METHODS: This research examined the methylation status of a region surrounding
      the NOTCH4 -25 C/T site in leukocyte genomic DNA and human brain regions. It also
      examined the polymorphism status of NOTCH4 -25 C/T. The sample included 40
      individuals (16 affected, 24 controls) and 31 regions of an adult human brain
      (from a single individual). RESULTS: This study established that the -25 C was
      the only cytosine which showed methylation in any of the blood or brain samples
      analyzed. Furthermore, -25 C (i) was always fully or partially methylated in
      blood (ii) was methylated in a similar pattern between the affected and controls
      in the blood (iii) was variably methylated in the brain, including completely
      methylated, partially methylated, subtly methylated or not methylated. It also
      established that the -25 C/T polymorphism was not associated to schizophrenia.
      CONCLUSION: The polymorphism and methylation analysis of NOTCH4 established that
      (i) the -25 C/T polymorphism and methylation status is not associated to
      schizophrenia in blood (ii) the -25 C is variably methylated in a region specific
      manner in the brain (iii) there is more variability observed within the brain of
      a single individual than in the blood among the individuals.

PMID- 21085057
TI  - What is the potential impact of adult circumcision on the HIV epidemic among men
      who have sex with men in San Francisco?
AB  - With the help of a community-based survey, we assess the potential effect of
      circumcision on the HIV epidemic among men who have sex with men (MSM) in San
      Francisco. Only a small minority of MSM would both derive benefit from
      circumcision (i.e., were uncircumcised, HIV-negative, predominantly insertive,
      and reported unprotected insertive anal sex) and be willing to participate in
      circumcision trials (0.7%) or be circumcised if proven effective as a prevention
      strategy (0.9%). Circumcision would have limited public health significance for
      MSM in San Francisco.

PMID- 21085058
TI  - Chlamydia trachomatis genotypes among men who have sex with men in Australia.
AB  - BACKGROUND: Chlamydia trachomatis is a common bacterial sexually transmitted
      infection in men who have sex with men (MSM), although little is known about its
      distribution in Australian MSM communities. METHODS: From 2004 to 2008, 612
      consecutive C. trachomatis positive anal swab and urine samples were collected
      for genotyping and quantification from MSM attending 2 sexual health centers
      (Melbourne and Sydney). RESULTS: The most common serovars detected were D
      (35.2%), G (32.7%), and J (17.7%), although these distributions changed
      significantly by year and city. C. trachomatis infections (2.8%) involved more
      than 1 serovar and only 1 lymphogranuloma venereum isolate was detected. The
      majority of serovar strains showed an identical omp1 genotype, with only 7.5%
      showing genotypic variability. Serovar G infections were not associated with
      overseas sexual activity; whilst individuals with serovar J were less likely to
      have had a prior C. trachomatis infection, and with serovar E were those who had
      prior C. trachomatis infection. Symptoms were present in 68% of urethral
      infections and 28% anal infections, and were associated with gonorrheal
      coinfection (13.8%), prior C. trachomatis infection (20.6%) and increasing age. A
      higher C. trachomatis load was identified in anal samples versus urine (1.48 *
      10(4) genome copies/anal swab; 3.72 * 10(3) copies/mL urine) and no association
      was made to concentration including the presence of symptoms and prior C.
      trachomatis infection. CONCLUSIONS: This is the largest study of C. trachomatis
      serovars in MSM: it is the first to report C. trachomatis rectal loads, and
      provides an overview on C. trachomatis serovars and genotypic variants that
      circulate in Australian MSM communities.

PMID- 21085056
TI  - Young women engaged in sex work in Phnom Penh, Cambodia, have high incidence of
      HIV and sexually transmitted infections, and amphetamine-type stimulant use: new
      challenges to HIV prevention and risk.
AB  - OBJECTIVES: To estimate prevalence and incidence of HIV and sexually transmitted
      infections (STI) and associated risk factors among young women working as sex
      workers (SWs) in Phnom Penh, Cambodia. METHODS: A prospective study of young (<29
      years) women working as SWs in brothels, entertainment establishments, and
      freelance. Sociodemographics, sexual risk, and use of amphetamine-type stimulants
      (ATS) ("yama" and "crystal") were assessed by self-report. HIV and STI (Chlamydia
      trachomatis and Neisseria gonorrhoeae) testing were conducted on blood and urine
      specimens, respectively. RESULTS: Baseline prevalences of HIV, C. trachomatis,
      and N. gonorrhoeae were 23%, 11.5%, and 7.8%, respectively. HIV incidence was 3.6
      per 100 person-years (95% confidence interval [CI], 1.2%-11.1%); STI incidence
      was 21.2 per 100 person-years (95% CI, 12.6%-35.8%). At baseline, 26.5% reported
      recent ATS use. HIV infection was associated with freelance SW (adjusted odds
      ratio, 5.85; 95% CI, 1.59-21.58) and younger age of first sex (<=15 years;
      adjusted odds ratio, 3.06; 95% CI, 1.01-8.46). Incident STI was associated with
      duration (per year) of SW (adjusted hazard ratio, 1.1; 95% CI, 1.1-1.2) and
      recent yama use (adjusted hazard ratio, 3.9; 95% CI, 1.5-10.3). CONCLUSIONS: HIV
      and STI infection rates were high among SWs working in various settings;
      freelancers had highest risk. ATS use was associated with incident STI. Venue of
      sex work and drug prevention should be considered in prevention programs.

PMID- 21085060
TI  - Long-term follow-up of 23 operational tolerant liver transplant recipients.
AB  - INTRODUCTION: This is a follow-up of a withdrawal study that we previously
      performed on 104 liver transplant patients in which immunosuppression was
      gradually withdrawn over a period of 3 years. Eighty-one patients were not able
      to be withdrawn (rejectors), and 23 patients were successfully weaned off
      immunosuppression (tolerants). METHODS: In this study, we present their follow-up
      after the end of the withdrawal study: we compared the results of the tolerant
      patients (n=23) with those of the rejectors (n=81). Follow-up was until February
      2010. RESULTS: Operational tolerant patients were off immunosuppression for an
      average of 7.27+/-0.28 years. Patient survival in the tolerant and the rejector
      groups was 63.66% and 74.25%, respectively (P=not significant). A patient in the
      rejector group received two retransplants for chronic rejection. In the rejector
      group, 19 patients presented 26 rejection episodes: clinically suspected (n=19)
      and biopsy-proven mild (n=4), moderate (n=2), and severe (n=1) rejection
      episodes. A tolerant patient had a moderate rejection episode of 5.3 years after
      immunosuppression withdrawal. In the rejector group, five patients received a
      kidney transplant and four more are on dialysis versus a tolerant patient on
      dialysis. Freedom from rejection in the tolerant and rejector groups was 95% and
      73%, respectively (P<0.05), and freedom from renal replacement treatment was
      83.33% vs. 44.58%, respectively (P=not significant). CONCLUSIONS: Long-term
      outcomes of operationally tolerant liver transplant patients are at least as good
      as those of control patients. Operational tolerance is not a permanent state, and
      continuous vigilance is required to detect rejection episodes.

PMID- 21085059
TI  - Single-nucleotide polymorphisms, acute rejection, and severity of tubulitis in
      kidney transplantation, accounting for center-to-center variation.
AB  - BACKGROUND: Acute rejection (AR) is associated with worse renal allograft
      outcomes. Therefore, this study investigated single-nucleotide polymorphisms
      (SNPs) to identify genetic variants associated with AR, accounting for center
      variation, in a multicenter, prospective, observation study. METHODS: We enrolled
      patients from six transplant centers, five in the United States and one in
      Canada. A total of 2724 SNPs were genotyped. We accounted for center variation in
      AR rates by stratifying by transplant center and using novel knowledge discovery
      methods. RESULTS: There was significant center variation in AR rates across the
      six transplant sites (P<0.0001). Accounting for this difference and clinical
      factors independently associated with AR, we identified 15 novel SNPs associated
      with AR with stratification by transplant center (P<0.05). We also identified 15
      novel SNPs associated with severity of tubulitis scores, after adjusting for
      transplant center and other clinical factors independently associated with
      severity of tubulitis (P<0.05). There was some overlap with one SNP associated
      with AR and also associated with severity of tubulitis, among the top 15 SNPs.
      CONCLUSION: Center-to-center variation is a major challenge to genomic studies
      focused on AR. The SNPs associated with AR and severity of tubulitis in this
      study will need to be validated in independent cohort of kidney transplant
      recipients.

PMID- 21085061
TI  - Glomerular filtration rate slopes have significantly improved among renal
      transplants in the United States.
AB  - INTRODUCTION: In recent years, the use of higher risk donor organs and steroid
      avoidance regimens with potential increased acute rejection risk have increased.
      We hypothesized that these patterns adversely affect changes in posttransplant
      renal function. METHODS: By using Scientific Registry of Transplant Recipients
      data and multivariable generalized linear models, we examined factors associated
      with slopes of estimated glomerular filtration rate (GFR; modification of diet in
      renal disease) from 6 to 12 months and 6 to 24 months posttransplant in solitary
      adult renal transplant recipients transplanted between 2003 and 2008 (n=91,241).
      We estimated GFR at each interval, analyzed changes within patients between
      follow-up intervals, and evaluated changes in 1-year graft and patient survival
      during the study period. RESULTS: GFR intercept at 6 months averaged 54.3
      mL/min/1.73 m2 (standard deviation [SD] 18.2 mL/min/1.73 m2). Decline in GFR
      between 6 and 12 months posttransplant averaged 0.69 mL/min/1.73 m2 (SD 10.9
      mL/min/1.73 m2) and between 6 and 24 months averaged 2.45 mL/min/1.73 m2 (SD 15.7
      mL/min/1.73 m2). However, the GFR decline was significantly attenuated during the
      study period among both deceased and living donor transplant recipients. Factors
      significantly associated with steeper GFR decline were increased pretransplant
      dialysis time, older donor age, diabetes as a primary diagnosis, low body mass
      index, African American race, retransplants, nonprivate insurance, and increased
      panel reactive antibody percent. Baseline or slope in renal function did not
      differ substantially by immunosuppressive regimen. One-year overall graft
      survival increased during the study period from 92.3% to 93.9%. CONCLUSIONS: GFR
      slopes and 1-year survival rates have improved in the United States independent
      of donor quality and immunosuppressive regimen. Findings may reflect increased
      skill in medical management and need further evaluation to determine whether
      short-term improvements translate to improved long-term survival.

PMID- 21085062
TI  - Induction of donor-specific tolerance using superagonistic CD28 antibody in rat
      renal allografts: regulatory T-cell expansion before engraftment may be
      important.
AB  - BACKGROUND: We hypothesized that a superagonistic monoclonal antibody specific
      for CD28 (CD28SA), which expands regulatory T cells (Tregs) in vivo, would
      prevent acute rejection and prolong the survival of renal allograft. METHODS: We
      examined whether CD28SA treatment induce donor-specific tolerance using our
      established rat renal allograft model (Wistar-Lewis). RESULTS: All control rats
      died within 13 days because of severe azotemia with marked destruction of graft
      tissue. In contrast, recipients treated with a triple injection of CD28SA (days 
      3, 0, and 3) showed good preservation of graft histology and function, with
      considerable infiltration of Tregs into the allografts; 92% of recipients
      survived for more than 100 days, and 77% survived by the day of harvest at 180
      days. These long-surviving recipients received secondary heterotopic bicardiac
      allografts from both donor-matched Wistar and third-party Brown Norway rats
      simultaneously 120 days after kidney transplantation, and seven of eight (87.5%)
      rats exhibited donor-specific tolerance, accepting the Wistar heart, but acutely
      rejecting the Brown Norway heart. Interestingly, a single injection of CD28SA 3
      days before (day -3), but not 3 days after (day 3), transplantation also induced
      donor-specific tolerance in some recipients. We then performed adoptive transfer
      of nonspecific CD4+CD25+ Tregs, purified from CD28SA-treated Lewis rats, with
      simultaneous injection of hepatocyte growth factor (500 MUg/kg/day,
      intravenously). The treatment induced significant prolongation of graft survival
      (P<0.0001 vs. control group), and five of eight (62.5%) recipients survived until
      the day of harvest at 180 days with successful induction of donor-specific
      tolerance. CONCLUSIONS: We have established a novel therapeutic approach for
      inducing donor-specific tolerance in rats with renal allografts.

PMID- 21085063
TI  - The role of direct presentation by donor dendritic cells in rejection of minor
      histocompatibility antigen-mismatched skin and hematopoietic cell grafts.
AB  - BACKGROUND: The success of transplantation is hampered by rejection of the graft
      by alloreactive T cells. Donor dendritic cells (DC) have been shown to be
      required for direct priming of immune responses to antigens from major
      histocompatibility complex-mismatched grafts. However, for immune responses to
      major histocompatibility complex-matched, minor histocompatibility (H) antigen
      mismatched grafts, the magnitude of the T-cell response to directly presented
      antigens is reduced, and the indirect pathway is more important. Therefore, we
      aimed to investigate the requirement for donor DC to directly present antigen
      from minor H antigen mismatched skin and hematopoietic grafts. METHODS:
      Langerhans cell- or conventional (c)DC-depleted skin or hematopoietic cells from
      male DC-specific diphtheria toxin receptor mice were grafted onto, or injected
      into, syngeneic female recipients, and survival of the male tissue was compared
      with nondepleted tissue. Activation of the alloreactive immune response was
      tracked by the expansion of T cells specific for male HY-derived epitopes.
      RESULTS: Our data demonstrate that depletion of donor Langerhans cell, dermal
      cDC, or both from skin grafts prolongs their survival but does not prevent
      rejection. Extended survival correlates with delayed expansion of HY peptide
      specific CD8 T cells. In addition, depletion of donor cDC delays rejection of
      male hematopoietic cells. CONCLUSIONS: Our results demonstrate for the first time
      that direct presentation of minor H antigens by donor DC is required for
      efficient rejection of skin and hematopoietic grafts by CD8 T cells. But, in the
      absence of donor DC, indirect presentation of minor antigens is sufficient to
      mediate the response.

PMID- 21085066
TI  - The generation of donor-specific CD4+CD25++CD45RA+ naive regulatory T cells in
      operationally tolerant patients after pediatric living-donor liver
      transplantation.
AB  - BACKGROUND: CD4+CD25++CD45RA+ cells (naive regulatory T cells [naive-Tregs]) have
      been identified as a functionally premature form of CD4+CD25+++CD45RA(-) cells
      (conventional-Tregs). However, their contribution to transplant tolerance remains
      to be elucidated. METHOD: We examined the frequency and the function of
      conventional and naive-Tregs in the peripheral blood derived from operationally
      tolerant patients after pediatric living-donor liver transplant (Gr-tol). The
      data were compared with those of patients who were unable to be weaned off
      immunosuppression due to rejection (group-intolerance [Gr-intol]), patients in
      the process of weaning immunosuppression (Gr-weaning) and healthy volunteers
      (group-healthy volunteers [Gr-vol]). RESULTS: In Gr-tol, the frequency of
      conventional-Tregs was significantly higher than that in Gr-vol and tended to be
      higher than that in Gr-intol. The frequency of naive-Tregs was significantly
      decreased in Gr-intol versus those in Gr-tol, -weaning, and -vol. In mixed
      lymphocyte reactions, donor-specific hyporesponsiveness of CD4+ cells was
      observed only in Gr-tol but not in the other groups. Depletion of conventional or
      naive-Tregs from CD4+ cells demonstrated that the suppressive properties of donor
      antigen-reactive conventional and naive-Tregs were upregulated compared with
      those of third-party antigen-reactive conventional and naive-Tregs in Gr-tol
      only. CONCLUSIONS: This is the first report providing detailed evidence that
      donor-specific naive-Tregs were generated and their suppressive properties were
      upregulated in the peripheral blood of tolerant patients, whereas their frequency
      was downregulated in intolerant patients. Therefore, we speculate that not only
      conventional-Tregs play a role in Tx tolerance but also the role of naive-Tregs
      is critical.

PMID- 21085064
TI  - Mixed chimerism, lymphocyte recovery, and evidence for early donor-specific
      unresponsiveness in patients receiving combined kidney and bone marrow
      transplantation to induce tolerance.
AB  - BACKGROUND: We have previously reported operational tolerance in patients
      receiving human leukocyte antigen-mismatched combined kidney and bone marrow
      transplantation (CKBMT). We now report on transient multilineage hematopoietic
      chimerism and lymphocyte recovery in five patients receiving a modified CKBMT
      protocol and evidence for early donor-specific unresponsiveness in one of these
      patients. METHODS: Five patients with end-stage renal disease received CKBMT from
      human leukocyte antigen-mismatched, haploidentical living-related donors after
      modified nonmyeloablative conditioning. Polychromatic flow cytometry was used to
      assess multilineage chimerism and lymphocyte recovery posttransplant. Limiting
      dilution analysis was used to assess helper T-lymphocyte reactivity to donor
      antigens. RESULTS: Transient multilineage mixed chimerism was observed in all
      patients, but chimerism became undetectable by 2 weeks post-CKBMT. A marked
      decrease in T- and B-lymphocyte counts immediately after transplant was followed
      by gradual recovery. Initially, recovering T cells were depleted of
      CD45RA+/CD45RO(-) "naive-like" cells, which have shown strong recovery in two
      patients, and CD4:CD8 ratios increased immediately after transplant but then
      declined markedly. Natural killer cells were enriched in the peripheral blood of
      all patients after transplant.For subject 2, a pretransplant limiting dilution
      assay revealed T helper cells recognizing both donor and third-party peripheral
      blood mononuclear cells. However, the antidonor response was undetectable by day
      24, whereas third-party reactivity persisted. CONCLUSION: These results
      characterize the transient multilineage mixed hematopoietic chimerism and
      recovery of lymphocyte subsets in patients receiving a modified CKBMT protocol.
      The observations are relevant to the mechanisms of donor-specific tolerance in
      this patient group.

PMID- 21085067
TI  - Technology and patient safety: only part of the solution.

PMID- 21085068
TI  - Improving communication in acute care.

PMID- 21085070
TI  - Acquired small bowel diverticular disease: a review.

PMID- 21085071
TI  - Alcohol and the pancreas.

PMID- 21085072
TI  - Surveillance for colorectal cancer in patients with inflammatory bowel disease.

PMID- 21085073
TI  - Naltrexone in the treatment of opioid dependence.

PMID- 21085074
TI  - Developmental coordination disorder.

PMID- 21085075
TI  - Medicine and management: crossing the divide.

PMID- 21085076
TI  - Interprofessional learning.

PMID- 21085077
TI  - An evaluation of the use of the mini-CEX in the foundation programme.

PMID- 21085078
TI  - Jean Henri Dunant: father of the Red Cross and Nobel laureate.
AB  - Today, the International Red Cross is the largest humanitarian organization in
      the world. This year marks the 100th anniversary of the death of its founder,
      Jean Henri Dunant. The details of his life and achievement are both incredible
      and sad.

PMID- 21085080
TI  - The acute medical abdomen: Henoch-Schonlein purpura presenting with peritonitis
      and nephritis.

PMID- 21085079
TI  - Pleural mesothelioma presenting as recurrent pneumothoraces.

PMID- 21085081
TI  - Tuberculous psoas abscess mimicking soft tissue tumour.

PMID- 21085082
TI  - Disclosure and anonymity in patient confidentiality.

PMID- 21085085
TI  - Should patients routinely be visited by the anaesthetist once they have left the
      recovery area?

PMID- 21085086
TI  - Microwave-assisted synthesis of novel 2,3-dihydro-4-pyridinones.
AB  - Novel 2,3-dihydro-4-pyridinones were synthesized via the reaction of curcumin and
      primary amines or amine acetates under microwave irradiation. Montmorillonite K
      10 was used as a catalyst. Reaction times did not exceed 120 s. The structures of
      the compounds were established by elemental analysis and from their mass, 1H- and
      13C-NMR spectra.

PMID- 21085087
TI  - Sorption speciation of lanthanides/actinides on minerals by TRLFS, EXAFS and DFT
      studies: a review.
AB  - Lanthanides/actinides sorption speciation on minerals and oxides by means of time
      resolved laser fluorescence spectroscopy (TRLFS), extended X-ray absorption fine
      structure spectroscopy (EXAFS) and density functional theory (DFT) is reviewed in
      the field of nuclear disposal safety research. The theoretical aspects of the
      methods are concisely presented. Examples of recent research results of
      lanthanide/actinide speciation and local atomic structures using TRLFS, EXAFS and
      DFT are discussed. The interaction of lanthanides/actinides with oxides and
      minerals as well as their uptake are also of common interest in radionuclide
      chemistry. Especially the sorption and inclusion of radionuclides into several
      minerals lead to an improvement in knowledge of minor components in solids. In
      the solid-liquid interface, the speciation and local atomic structures of
      Eu(III), Cm(III), U(VI), and Np(IV/VI) in several natural and synthetic minerals
      and oxides are also reviewed and discussed. The review is important to understand
      the physicochemical behavior of lanthanides/actinides at a molecular level in the
      natural environment.

PMID- 21085088
TI  - Update: cholera outbreak --- Haiti, 2010.
AB  - On October 19, 2010, the Haitian Ministry of Public Health and Population (MSPP)
      was notified of unusually high numbers of patients from Artibonite and Centre
      departments who had acute watery diarrhea and dehydration, in some cases leading
      to death. Within 4 days, the National Public Health Laboratory (LNSP) in Haiti
      isolated Vibrio cholerae serogroup O1, serotype Ogawa, from stool specimens
      obtained from patients in the affected areas by an investigation team from MSPP
      and CDC Haiti. This report describes the investigation of the initial cases, the
      ongoing outbreak of cholera in Haiti, and initial control measures. Since the
      initial identification of cholera, the outbreak has expanded to include cases in
      seven of Haiti's 10 departments and the capital city of Port-au-Prince. As of
      November 13, MSPP had reported 16,111 persons hospitalized with acute watery
      diarrhea and 992 cholera deaths, 620 of which occurred among hospitalized
      patients. Prevention and control measures implemented by MSPP with assistance
      from governmental and nongovernmental partners include 1) providing better access
      to treated drinking water; 2) providing education on improvement of sanitation,
      hygiene, and food preparation practices; 3) advising ill persons to begin using
      oral rehydration solution immediately and seek health care at the onset of watery
      diarrhea; 4) enhancing cholera treatment capacity at existing health-care
      institutions; and 5) establishing cholera treatment centers.

PMID- 21085089
TI  - Occupational transmission of Neisseria meningitidis --- California, 2009.
AB  - Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis .
      The case-fatality rate for meningococcal disease is 10%--14%; survivors can
      experience brain damage, hearing loss, limb loss, and learning disabilities . On
      December 11, 2009, the California Department of Public Health (CDPH) initiated an
      investigation of two secondary cases of meningococcal disease in a police officer
      and a respiratory therapist following occupational contact with an unconscious
      adult. This report describes the events surrounding occupational transmission of
      N. meningitidis and recommends measures to control and prevent secondary
      transmission of N. meningitidis. Breaches in infection control, notification
      delays, and lack of worker exposure assessment and postexposure chemoprophylaxis
      (PEP) likely contributed to secondary cases. Employers should provide adequate
      infection-control training to staff members, PEP to exposed workers, and report
      notifiable diseases promptly.

PMID- 21085090
TI  - Smoking restrictions in large-hub airports --- United States, 2002 and 2010.
AB  - Secondhand smoke (SHS) exposure causes death and disease in both nonsmoking
      adults and children, including cancer, cardiovascular and respiratory diseases.
      SHS exposure causes an estimated 46,000 heart disease deaths and 3,400 lung
      cancer deaths among U.S. nonsmoking adults annually. Adopting policies that
      completely eliminate smoking in all indoor areas is the only effective way to
      eliminate involuntary SHS exposure. In 2009, an estimated 696 million aircraft
      passenger boardings occurred in the United States. A 2002 survey of airport
      smoking policies found that 42% of 31 large-hub U.S. airports had policies
      requiring all indoor areas to be smoke-free. To update that finding, CDC analyzed
      the smoking policies of airports categorized as large-hub in 2010. This report
      summarizes the results of that analysis, which found that, although 22 (76%) of
      the 29 large-hub airports surveyed were smoke-free indoors, seven airports
      permitted smoking in certain indoor locations, including three of the five
      busiest airports. Although a majority of airports reported having specifically
      designated smoking areas outdoors in 2010 (79%) and/or prohibiting smoking within
      a minimum distance of entryways (69%), no airport completely prohibited smoking
      on all airport property. Smoke-free policies at the state, local, or airport
      authority level are needed for all airports to protect air travelers and workers
      at airports from SHS.

PMID- 21085091
TI  - Syringe exchange programs --- United States, 2008.
AB  - Persons who inject drugs should use a new, sterile needle and syringe for each
      injection. Syringe exchange programs (SEPs) provide free sterile syringes and
      collect used syringes from injection-drug users (IDUs) to reduce transmission of
      bloodborne pathogens, including human immunodeficiency virus (HIV), hepatitis B
      virus, and hepatitis C virus (HCV). As of March 2009, a total of 184 SEPs were
      known to be operating in 36 states, the District of Columbia (DC), and Puerto
      Rico (North American Syringe Exchange Network [NASEN], unpublished data, 2009).
      Of these, 123 (67%) SEP directors participated in a mail/telephone survey
      conducted by NASEN and Beth Israel Medical Center (New York, New York) that
      covered program operations for the calendar year 2008. To characterize SEPs in
      the United States, this report summarizes the findings from that survey and
      compares them with previous SEP survey results from the period 1994-2007. In
      2008, the 123 SEPs reported exchanging 29.1 million syringes and had budgets
      totaling $21.3 million, of which 79% came from state and local governments. Most
      of the SEPs reported offering preventive health and clinical services in addition
      to basic syringe exchange: 87% offered HIV counseling and testing, 65% offered
      hepatitis C counseling and testing, 55% offered sexually transmitted disease
      screening, and 31% offered tuberculosis screening; 89% provided referrals to
      substance abuse treatment. Providing comprehensive prevention services and
      referrals to IDUs, such as those offered by many SEPs, can help reduce the spread
      of bloodborne infections and should increase access to health care and substance
      abuse treatment, thus serving as an effective public health approach for this
      population.

PMID- 21085092
TI  - Visualisation and quantification of intracellular interactions of Neisseria
      meningitidis and human alpha-actinin by confocal imaging.
AB  - The Opc protein of Neisseria meningitidis (Nm, meningococcus) is a surface
      expressed integral outer membrane protein, which can act as an adhesin and an
      effective invasin for human epithelial and endothelial cells. We have identified
      endothelial surface-located integrins as major receptors for Opc, a process which
      requires Opc to first bind to integrin ligands such as vitronectin and via these
      to the cell-expressed receptors(1). This process leads to bacterial invasion of
      endothelial cells(2). More recently, we observed an interaction of Opc with a 100
      kDa protein found in whole cell lysates of human cells(3). We initially observed
      this interaction when host cell proteins separated by electrophoresis and blotted
      on to nitrocellulose were overlaid with Opc-expressing Nm. The interaction was
      direct and did not involve intermediate molecules. By mass spectrometry, we
      established the identity of the protein as alpha-actinin. As no surface expressed
      alpha-actinin was found on any of the eight cell lines examined, and as Opc
      interactions with endothelial cells in the presence of serum lead to bacterial
      entry into the target cells, we examined the possibility of the two proteins
      interacting intracellularly. For this, cultured human brain microvascular
      endothelial cells (HBMECs) were infected with Opc-expressing Nm for extended
      periods and the locations of internalised bacteria and alpha-actinin were
      examined by confocal microscopy. We observed time-dependent increase in
      colocalisation of Nm with the cytoskeletal protein, which was considerable after
      an eight hour period of bacterial internalisation. In addition, the use of
      quantitative imaging software enabled us to obtain a relative measure of the
      colocalisation of Nm with alpha-actinin and other cytoskeletal proteins. Here we
      present a protocol for visualisation and quantification of the colocalisation of
      the bacterium with intracellular proteins after bacterial entry into human
      endothelial cells, although the procedure is also applicable to human epithelial
      cells.

PMID- 21085093
TI  - Chronic imaging of mouse visual cortex using a thinned-skull preparation.
AB  - In vivo imaging using two-photon laser scanning microscopy (2PLSM) allows the
      study of living cells and neuronal processes in the intact brain. The technique
      presented here allows the imaging of the same area of the brain at several time
      points (chronic imaging) with microscopic resolution allowing the tracking of
      dendritic spines which are the small structures that represent the majority of
      postsynaptic excitatory sites in the CNS. The ability to clearly resolve fine
      cortical structures over several time points has many advantages, specifically in
      the study of brain plasticity in which morphological changes at synapses and
      circuit remodeling may help explain underlying mechanisms. In this video and
      supplementary material, we show a protocol for chronic in vivo imaging of the
      intact brain using a thinned-skull preparation. The thinned-skull preparation is
      a minimally invasive approach, which avoids potential damage to the dura and/or
      cortex, thus reducing the onset of an inflammatory response. When this protocol
      is performed correctly, it is possible to clearly monitor changes in dendritic
      spine characteristics in the intact brain over a prolonged period of time.

PMID- 21085094
TI  - Oral administration of rotenone using a gavage and image analysis of alpha
      synuclein inclusions in the enteric nervous system.
AB  - In Parkinson's disease (PD) patients, the associated pathology follows a
      characteristic pattern involving inter alia the enteric nervous system (ENS)
      (1,2), the olfactory bulb (OB), the dorsal motor nucleus of the vagus (DMV)(3),
      the intermediolateral nucleus of the spinal cord (4) and the substantia nigra,
      providing the basis for the neuropathological staging of the disease(4,5). The
      ENS and the OB are the most exposed nervous structures and the first ones to be
      affected. Interestingly, PD has been related to pesticide exposure(6-8). Here we
      show in detail two methods used in our previous study (9). In order to analyze
      the effects of rotenone acting locally on the ENS, we administered rotenone using
      a gavage to one-year old C57/BL6 mice. Rotenone is a widely used pesticide that
      strongly inhibits mitochondrial Complex I (10). It is highly lipophylic and
      poorly absorbed in the gastrointestinal tract (11). Our results showed that the
      administration of 5 mg/kg of rotenone did not inhibit mitochondrial Complex I
      activity in the muscle or the brain. Thus, suggesting that using our
      administration method rotenone did not cross the hepatoportal system and was
      acting solely on the ENS. Here we show a method to administer pesticides using a
      gavage and the image analysis protocol used to analyze the effects of the
      pesticide in alpha-synuclein accumulation in the ENS. The first part shows a
      method that allows intragastric administration of pesticides (rotenone) at a
      desired precise concentration. The second method shows a semi-automatic image
      analysis protocol to analyze alpha-synuclein accumulation in the ENS using an
      image analysis software.

PMID- 21085095
TI  - Isolation and culture of avian embryonic valvular progenitor cells.
AB  - Proper formation and function of embryonic heart valves is critical for
      developmental progression. The early embryonic heart is a U-shaped tube of
      endocardium surrounded by myocardium. The myocardium secretes cardiac jelly, a
      hyaluronan-rich gelatinous matrix, into the atrioventricular (AV) junction and
      outflow tract (OFT) lumen. At stage HH14 valvulogenesis begins when a subset of
      endocardial cells receive signals from the myocardium, undergo endocardial to
      mesenchymal transformation (EMT), and invade the cardiac jelly. At stage HH25 the
      valvular cushions are fully mesenchymalized, and it is this mesenchyme that
      eventually forms the valvular and septal apparatus of the heart. Understanding
      the mechanisms that initiate and modulate the process of EMT and cell
      differentiation are important because of their connection to serious congenital
      heart defects. In this study we present methods to isolate pre-EMT endocardial
      and post-EMT mesenchymal cells, which are the two different cell phenotypes of
      the prevalvular cushion. Pre-EMT endocardial cells can be cultured with or
      without the myocardium. Post-EMT AV cushion mesenchymal cells can be cultured
      inside mechanically constrained or stress-free collagen gels. These 3D in vitro
      models mimic key valvular morphogenic events and are useful for deconstructing
      the mechanisms of early and late stage valvulogenesis.

PMID- 21085096
TI  - The organotypic hippocampal slice culture model for examining neuronal injury.
AB  - Organotypic hippocampal slice culture is an in vitro method to examine mechanisms
      of neuronal injury in which the basic architecture and composition of the
      hippocampus is relatively preserved (1). The organotypic culture system allows
      for the examination of neuronal, astrocytic and microglial effects, but as an ex
      vivo preparation, does not address effects of blood flow, or recruitment of
      peripheral inflammatory cells. To that end, this culture method is frequently
      used to examine excitotoxic and hypoxic injury to pyramidal neurons of the
      hippocampus, but has also been used to examine the inflammatory response. Herein
      we describe the methods for generating hippocampal slice cultures from postnatal
      rodent brain, administering toxic stimuli to induce neuronal injury, and assaying
      and quantifying hippocampal neuronal death.

PMID- 21085097
TI  - Assessing two-dimensional crystallization trials of small membrane proteins for
      structural biology studies by electron crystallography.
AB  - Electron crystallography has evolved as a method that can be used either
      alternatively or in combination with three-dimensional crystallization and X-ray
      crystallography to study structure-function questions of membrane proteins, as
      well as soluble proteins. Screening for two-dimensional (2D) crystals by
      transmission electron microscopy (EM) is the critical step in finding,
      optimizing, and selecting samples for high-resolution data collection by cryo-EM.
      Here we describe the fundamental steps in identifying both large and ordered, as
      well as small 2D arrays, that can potentially supply critical information for
      optimization of crystallization conditions. By working with different
      magnifications at the EM, data on a range of critical parameters is obtained.
      Lower magnification supplies valuable data on the morphology and membrane size.
      At higher magnifications, possible order and 2D crystal dimensions are
      determined. In this context, it is described how CCD cameras and online-Fourier
      Transforms are used at higher magnifications to assess proteoliposomes for order
      and size. While 2D crystals of membrane proteins are most commonly grown by
      reconstitution by dialysis, the screening technique is equally applicable for
      crystals produced with the help of monolayers, native 2D crystals, and ordered
      arrays of soluble proteins. In addition, the methods described here are
      applicable to the screening for 2D crystals of even smaller as well as larger
      membrane proteins, where smaller proteins require the same amount of care in
      identification as our examples and the lattice of larger proteins might be more
      easily identifiable at earlier stages of the screening.

PMID- 21085098
TI  - Performing and processing FNA of anterior fat pad for amyloid.
AB  - Historically, heart, liver, and kidney biopsies were performed to demonstrate
      amyloid deposits in amyloidosis. Since the clinical presentation of this disease
      is so variable and non-specific, the associated risks of these biopsies are too
      great for the diagnostic yield. Other sites that have a lower biopsy risk, such
      as skin or gingival, are also relatively invasive and expensive. In addition,
      these biopsies may not always have sufficient amyloid deposits to establish a
      diagnosis. Fat pad aspiration has demonstrated good clinical correlation with low
      cost and minimal morbidity. However, there are no standardized protocols for
      performing this procedure or processing the aspirated specimen, which leads to
      variable and nonreproducible results. The most frequently utilized modality for
      detecting amyloid in tissue is an apple-green birefringence on Congo red stained
      sections using a polarizing microscope. This technique requires cell block
      preparation of aspirated material. Unfortunately, patients presenting in early
      stage of amyloidosis have minimal amounts of amyloid which greatly reduces the
      sensitivity of Congo red stained cell block sections of fat pad aspirates.
      Therefore, ultrastructural evaluation of fat pad aspirates by electron microscopy
      should be utilized, given its increased sensitivity for amyloid detection. This
      article demonstrates a simple and reproducible procedure for performing anterior
      fat pad aspiration for the detection of amyloid utilizing both Congo red staining
      of cell block sections and electron microscopy for ultrastructural
      identification.

PMID- 21085099
TI  - Comprehensive & cost effective laboratory monitoring of HIV/AIDS: an African role
      model.
AB  - We present the video about assisting anti-retroviral therapy (ART) by an apt
      laboratory service - representing a South-African role model for economical large
      scale diagnostic testing. In the low-income countries inexpensive ART has
      transformed the prospects for the survival of HIV seropositive patients but there
      are doubts whether there is a need for the laboratory monitoring of ART and at
      what costs - in situations when the overall quality of pathology services can
      still be very low. The appropriate answer is to establish economically sound
      services with better coordination and stricter internal quality assessment than
      seen in western countries. This video, photographed at location in the National
      Health Laboratory Services (NHLS-SA) at the Witwatersrand University,
      Johannesburg, South Africa, provides such a coordinated scheme expanding the
      original 2-color CD4-CD45 PanLeucoGating strategy (PLG). Thus the six modules of
      the video presentation reveal the simplicity of a 4-color flow cytometric assay
      to combine haematological, immunological and virology-related tests in a single
      tube. These video modules are: (i) the set-up of instruments; (ii) sample
      preparations; (iii) testing absolute counts and monitoring quality for each
      sample by bead-count-rate; (iv) the heamatological CD45 test for white cell
      counts and differentials; (v) the CD4 counts, and (vi) the activation of CD8+ T
      cells measured by CD38 display, a viral load related parameter. The potential
      cost-savings are remarkable. This arrangement is a prime example for the
      feasibility of performing > 800-1000 tests per day with a stricter quality
      control than that applied in western laboratories, and also with a transfer of
      technology to other laboratories within a NHLS-SA network. Expert advisors,
      laboratory managers and policy makers who carry the duty of making decisions
      about introducing modern medical technology are frequently not in a position to
      see the latest technical details as carried out in the large regional
      laboratories with huge burdens of workload. Hence this video shows details of
      these new developments.

PMID- 21085100
TI  - Label-free in situ imaging of lignification in plant cell walls.
AB  - Meeting growing energy demands safely and efficiently is a pressing global
      challenge. Therefore, research into biofuels production that seeks to find cost
      effective and sustainable solutions has become a topical and critical task.
      Lignocellulosic biomass is poised to become the primary source of biomass for the
      conversion to liquid biofuels. However, the recalcitrance of these plant cell
      wall materials to cost-effective and efficient degradation presents a major
      impediment for their use in the production of biofuels and chemicals. In
      particular, lignin, a complex and irregular poly-phenylpropanoid heteropolymer,
      becomes problematic to the postharvest deconstruction of lignocellulosic biomass.
      For example in biomass conversion for biofuels, it inhibits saccharification in
      processes aimed at producing simple sugars for fermentation. The effective use of
      plant biomass for industrial purposes is in fact largely dependent on the extent
      to which the plant cell wall is lignified. The removal of lignin is a costly and
      limiting factor and lignin has therefore become a key plant breeding and genetic
      engineering target in order to improve cell wall conversion. Analytical tools
      that permit the accurate rapid characterization of lignification of plant cell
      walls become increasingly important for evaluating a large number of breeding
      populations. Extractive procedures for the isolation of native components such as
      lignin are inevitably destructive, bringing about significant chemical and
      structural modifications. Analytical chemical in situ methods are thus invaluable
      tools for the compositional and structural characterization of lignocellulosic
      materials. Raman microscopy is a technique that relies on inelastic or Raman
      scattering of monochromatic light, like that from a laser, where the shift in
      energy of the laser photons is related to molecular vibrations and presents an
      intrinsic label-free molecular "fingerprint" of the sample. Raman microscopy can
      afford non-destructive and comparatively inexpensive measurements with minimal
      sample preparation, giving insights into chemical composition and molecular
      structure in a close to native state. Chemical imaging by confocal Raman
      microscopy has been previously used for the visualization of the spatial
      distribution of cellulose and lignin in wood cell walls. Based on these earlier
      results, we have recently adopted this method to compare lignification in wild
      type and lignin-deficient transgenic Populus trichocarpa (black cottonwood) stem
      wood. Analyzing the lignin Raman bands in the spectral region between 1,600 and
      1,700 cm-1, lignin signal intensity and localization were mapped in situ. Our
      approach visualized differences in lignin content, localization, and chemical
      composition. Most recently, we demonstrated Raman imaging of cell wall polymers
      in Arabidopsis thaliana with lateral resolution that is sub-MUm. Here, this
      method is presented affording visualization of lignin in plant cell walls and
      comparison of lignification in different tissues, samples or species without
      staining or labeling of the tissues.

PMID- 21085101
TI  - Fertilization of Xenopus oocytes using the host transfer method.
AB  - Studying the contribution of maternally inherited molecules to vertebrate early
      development is often hampered by the time and expense necessary to generate
      maternal-effect mutant animals. Additionally, many of the techniques to
      overexpress or inhibit gene function in organisms such as Xenopus and zebrafish
      fail to sufficiently target critical maternal signaling pathways, such as Wnt
      signaling. In Xenopus, manipulating gene function in cultured oocytes and
      subsequently fertilizing them can ameliorate these problems to some extent.
      Oocytes are manually defolliculated from donor ovary tissue, injected or treated
      in culture as desired, and then stimulated with progesterone to induce
      maturation. Next, the oocytes are introduced into the body cavity of an ovulating
      host female frog, whereupon they will be translocated through the host's oviduct
      and acquire modifications and jelly coats necessary for fertilization. The
      resulting embryos can then be raised to the desired stage and analyzed for the
      effects of any experimental perturbations. This host-transfer method has been
      highly effective in uncovering basic mechanisms of early development and allows a
      wide range of experimental possibilities not available in any other vertebrate
      model organism.

PMID- 21085102
TI  - An allele-specific gene expression assay to test the functional basis of genetic
      associations.
AB  - The number of significant genetic associations with common complex traits is
      constantly increasing. However, most of these associations have not been
      understood at molecular level. One of the mechanisms mediating the effect of DNA
      variants on phenotypes is gene expression, which has been shown to be
      particularly relevant for complex traits. This method tests in a cellular context
      the effect of specific DNA sequences on gene expression. The principle is to
      measure the relative abundance of transcripts arising from the two alleles of a
      gene, analysing cells which carry one copy of the DNA sequences associated with
      disease (the risk variants). Therefore, the cells used for this method should
      meet two fundamental genotypic requirements: they have to be heterozygous both
      for DNA risk variants and for DNA markers, typically coding polymorphisms, which
      can distinguish transcripts based on their chromosomal origin. DNA risk variants
      and DNA markers do not need to have the same allele frequency but the phase
      (haplotypic) relationship of the genetic markers needs to be understood. It is
      also important to choose cell types which express the gene of interest. This
      protocol refers specifically to the procedure adopted to extract nucleic acids
      from fibroblasts but the method is equally applicable to other cells types
      including primary cells. DNA and RNA are extracted from the selected cell lines
      and cDNA is generated. DNA and cDNA are analysed with a primer extension assay,
      designed to target the coding DNA markers. The primer extension assay is carried
      out using the MassARRAY (Sequenom) platform according to the manufacturer's
      specifications. Primer extension products are then analysed by matrix-assisted
      laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF/MS).
      Because the selected markers are heterozygous they will generate two peaks on the
      MS profiles. The area of each peak is proportional to the transcript abundance
      and can be measured with a function of the MassARRAY Typer software to generate
      an allelic ratio (allele 1: allele 2) calculation. The allelic ratio obtained for
      cDNA is normalized using that measured from genomic DNA, where the allelic ratio
      is expected to be 1:1 to correct for technical artifacts. Markers with a
      normalised allelic ratio significantly different to 1 indicate that the amount of
      transcript generated from the two chromosomes in the same cell is different,
      suggesting that the DNA variants associated with the phenotype have an effect on
      gene expression. Experimental controls should be used to confirm the results.

PMID- 21085103
TI  - Cargo loading onto kinesin powered molecular shuttles.
AB  - Cells have evolved sophisticated molecular machinery, such as kinesin motor
      proteins and microtubule filaments, to support active intracellular transport of
      cargo. While kinesins tail domain binds to a variety of cargoes, kinesins head
      domains utilize the chemical energy stored in ATP molecules to step along the
      microtubule lattice. The long, stiff microtubules serve as tracks for long
      distance intracellular transport. These motors and filaments can also be employed
      in microfabricated synthetic environments as components of molecular shuttles. In
      a frequently used design, kinesin motors are anchored to the track surface
      through their tails, and functionalized microtubules serve as cargo carrying
      elements, which are propelled by these motors. These shuttles can be loaded with
      cargo by utilizing the strong and selective binding between biotin and
      streptavidin. The key components (biotinylated tubulin, streptavidin, and
      biotinylated cargo) are commercially available. Building on the classic inverted
      motility assay, the construction of molecular shuttles is detailed here. Kinesin
      motor proteins are adsorbed to a surface precoated with casein; microtubules are
      polymerized from biotinylated tubulin, adhered to the kinesin and subsequently
      coated with rhodamine-labeled streptavidin. The ATP concentration is maintained
      at subsaturating concentration to achieve a microtubule gliding velocity optimal
      for loading cargo. Finally, biotinylated fluorescein-labeled nanospheres are
      added as cargo. Nanospheres attach to microtubules as a result of collisions
      between gliding microtubules and nanospheres adhering to the surface. The
      protocol can be readily modified to load a variety of cargoes such as
      biotinylated DNA, quantum dots or a wide variety of antigens via biotinylated
      antibodies.

PMID- 21085104
TI  - The C-seal: a biofragmentable drain protecting the stapled colorectal anastomosis
      from leakage.
AB  - Colorectal anastomotic leakage (AL) is a serious complication in colorectal
      surgery leading to high morbidity and mortality rates. The incidence of AL varies
      between 2.5 and 20%. Over the years, many strategies aimed at lowering the
      incidence of anastomotic leakage have been examined. The cause of AL is probably
      multifactorial. Etiological factors include insufficient arterial blood supply,
      tension on the anastomosis, hematoma and/or infection at the anastomotic site,
      and co-morbid factors of the patient as diabetes and atherosclerosis.
      Furthermore, some anastomoses may be insufficient from the start due to technical
      failure. Currently a new device is developed in our institute aimed at protecting
      the colorectal anastomosis and lowering the incidence of AL. This so called C
      seal is a biofragmentable drain, which is stapled to the anastomosis with the
      circular stapler. It covers the luminal side of the colorectal anastomosis
      thereby preventing leakage. The C-seal is a thin-walled tube-like drain, with an
      approximate diameter of 4 cm and an approximate length of 25 cm. It is a tubular
      device composed of biodegradable polyurethane. Two flaps with adhesive tape are
      found at one end of the tube. These flaps are used to attach the C-seal to the
      anvil of the circular stapler, so that after the anastomosis is made the C-seal
      can be pulled through the anus. The C-seal remains in situ for at least 10 days.
      Thereafter it will lose strength and will degrade to be secreted from the body
      together with the gastrointestinal natural contents. The C-seal does not prevent
      the formation of dehiscences. However, it prevents extravasation of faeces into
      the peritoneal cavity. This means that a gap at the anastomotic site does not
      lead to leakage. Currently, a phase II study testing the C-seal in 35 patients
      undergoing (colo-)rectal resection with stapled anastomosis is recruiting. The C
      seal can be used in both open procedures as well as laparoscopic procedures. The
      C-seal is only applied in stapled anastomoses within 15 cm from the anal verge.
      In the video, application of the C-seal is shown in an open extended sigmoid
      resection in a patient suffering from diverticular disease with a stenotic colon.

PMID- 21085105
TI  - Experimental models for study of retinal pigment epithelial physiology and
      pathophysiology.
AB  - We have developed a cell culture procedure that can produce large quantities of
      confluent monolayers of primary human fetal retinal pigment epithelium (hfRPE)
      cultures with morphological, physiological and genetic characteristics of native
      human RPE. These hfRPE cell cultures exhibit heavy pigmentation, and electron
      microscopy show extensive apical membrane microvilli. The junctional complexes
      were identified with immunofluorescence labeling of various tight junction
      proteins. Epithelial polarity and function of these easily reproducible primary
      cultures closely resemble previously studied mammalian models of native RPE,
      including human. These results were extended by the development of therapeutic
      interventions in several animal models of human eye disease. We have focused on
      strategies for the removal of abnormal fluid accumulation in the retina or
      subretinal space. The extracellular subretinal space separates the photoreceptor
      outer segments and the apical membrane of the RPE and is critical for maintenance
      of retinal attachments and a whole host of RPE/retina interactions.

PMID- 21085106
TI  - Quantitative measurement of GLUT4 translocation to the plasma membrane by flow
      cytometry.
AB  - Glucose is the main source of energy for the body, requiring constant regulation
      of its blood concentration. Insulin release by the pancreas induces glucose
      uptake by insulin-sensitive tissues, most notably the brain, skeletal muscle, and
      adipocytes. Patients suffering from type-2 diabetes and/or obesity often develop
      insulin resistance and are unable to control their glucose homeostasis. New
      insights into the mechanisms of insulin resistance may provide new treatment
      strategies for type-2 diabetes. The GLUT family of glucose transporters consists
      of thirteen members distributed on different tissues throughout the body. Glucose
      transporter type 4 (GLUT4) is the major transporter that mediates glucose uptake
      by insulin sensitive tissues, such as the skeletal muscle. Upon binding of
      insulin to its receptor, vesicles containing GLUT4 translocate from the cytoplasm
      to the plasma membrane, inducing glucose uptake. Reduced GLUT4 translocation is
      one of the causes of insulin resistance in type-2 diabetes. The translocation of
      GLUT4 from the cytoplasm to the plasma membrane can be visualized by
      immunocytochemistry, using fluorophore-conjugated GLUT4-specific antibodies.
      Here, we describe a technique to quantify total amounts of GLUT4 translocation to
      the plasma membrane of cells during a chosen duration, using flow cytometry. This
      protocol is rapid (less than 4 hours, including incubation with insulin) and
      allows the analysis of as few as 3,000 cells or as many as 1 million cells per
      condition in a single experiment. It relies on anti-GLUT4 antibodies directed to
      an external epitope of the transporter that bind to it as soon as it is exposed
      to the extracellular medium after translocation to the plasma membrane.

PMID- 21085107
TI  - Detection of functional matrix metalloproteinases by zymography.
AB  - Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases. They degrade
      proteins by cleavage of peptide bonds. More than twenty MMPs have been identified
      and are separated into six groups based on their structure and substrate
      specificity (collagenases, gelatinases, membrane type [MT-MMP], stromelysins,
      matrilysins, and others). MMPs play a critical role in cell invasion, cartilage
      degradation, tissue remodeling, wound healing, and embryogenesis. They therefore
      participate in both normal processes and in the pathogenesis of many diseases,
      such as rheumatoid arthritis, cancer, or chronic obstructive pulmonary disease.
      Here, we will focus on MMP-2 (gelatinase A, type IV collagenase), a widely
      expressed MMP. We will demonstrate how to detect MMP-2 in cell culture
      supernatants by zymography, a commonly used, simple, and yet very sensitive
      technique first described in 1980 by C. Heussen and E.B. Dowdle. This technique
      is semi-quantitative, it can therefore be used to determine MMP levels in test
      samples when known concentrations of recombinant MMP are loaded on the same gel.
      Solutions containing MMPs (e.g. cell culture supernatants, urine, or serum) are
      loaded onto a polyacrylamide gel containing sodium dodecyl sulfate (SDS; to
      linearize the proteins) and gelatin (substrate for MMP-2). The sample buffer is
      designed to increase sample viscosity (to facilitate gel loading), provide a
      tracking dye (bromophenol blue; to monitor sample migration), provide denaturing
      molecules (to linearize proteins), and control the pH of the sample. Proteins are
      then allowed to migrate under an electric current in a running buffer designed to
      provide a constant migration rate. The distance of migration is inversely
      correlated with the molecular weight of the protein (small proteins move faster
      through the gel than large proteins do and therefore migrate further down the
      gel). After migration, the gel is placed in a renaturing buffer to allow proteins
      to regain their tertiary structure, necessary for enzymatic activity. The gel is
      then placed in a developing buffer designed to allow the protease to digest its
      substrate. The developing buffer also contains p-aminophenylmercuric acetate
      (APMA) to activate the non-proteolytic pro-MMPs into active MMPs. The next step
      consists of staining the substrate (gelatin in our example). After washing the
      excess dye off the gel, areas of protease digestion appear as clear bands. The
      clearer the band, the more concentrated the protease it contains. Band staining
      intensity can then be determined by densitometry, using a software such as
      ImageJ, allowing for sample comparison.

PMID- 21085108
TI  - Antigen specific killing assay using CFSE labeled target cells.
AB  - Carboxyfluorescein diacetate succinimidyl ester (CFSE) can be used to easily and
      quickly label a cell population of interest for in vivo investigation. This
      labeling has classically been used to study proliferation and migration. In the
      method presented here, we have shortened the timeline after adoptive transfer to
      look at survival and killing of epitope specific CFSE labeled target cells. The
      level of specific killing of a CD8 + T cell clone can indicate the quality of the
      response, as their quantity may be misleading. Specific CD8+ T cells can become
      functionally exhausted over time with a decline in cytokine production and
      killing. Also, certain CD8 + T cell clones may not kill as well as others with
      differing TCR specificities. For effective Cell Mediated Immunity (CMI), antigens
      must be identified that produce not only adequate numbers of responding T cells,
      but also functionally robust responding T cells. Here we assess the percent cell
      specific killing of two peptide specific T cell clones in BALB/c mice.

PMID- 21085109
TI  - mTOR and rapamycin in the kidney: signaling and therapeutic implications beyond
      immunosuppression.
AB  - The immunosuppressive drug rapamycin has helped to identify a large signaling
      network around the target of rapamycin (TOR) protein that integrates information
      on nutrient availability and growth factors to control protein synthesis and cell
      size. Studies using rapamycin in animal models of kidney disease indicate that
      mTOR deregulation has a role in glomerular disease, polycystic kidney disease,
      and renal cancer. The role of mTOR activation in podocytes is context dependent,
      and indirect evidence suggests that mTOR may have a role in chronic podocyte
      loss. Several lines of evidence show that cyst formation in polycystic kidney
      disease (PKD) involves mTOR activation and its upstream regulator TSC. Polycystin
      1 regulates mTOR activity through different pathways, and TSC intersects with the
      primary cilium, a crucial cell organelle in the pathogenesis of PKD. Data from
      hamartoma syndromes provide clear evidence that mutation of members of the mTOR
      network results in renal cancers. The detailed analysis of renal cell carcinomas
      has revealed a positive feedback loop involving VHL and mTOR. Rapamycin and its
      derivatives have been approved for the treatment of advanced renal cancer and are
      being investigated for the treatment of PKD. Discrepancies exist between the
      effects of rapamycin in animal models and the clinical experience with patients,
      precluding the widespread use of mTOR inhibitors in kidney disease. The details
      of mTOR signaling in the kidney need to be clarified to hopefully develop
      targeted treatments for renal disease in the future.

PMID- 21085110
TI  - 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and
      oxidative stress in a hyperoxaluric rat model.
AB  - Adhesion of calcium oxalate (CaOx) crystals to kidney cells may be a key event in
      the pathogenesis of kidney stones associated with marked hyperoxaluria.
      Previously, we found that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG),
      isolated from a traditional medicinal herb, reduced CaOx crystal adhesion to
      renal epithelial cells by acting on the cells as well as on the crystal surface.
      Here we used the ethylene glycol (EG)-mediated hyperoxaluric rat model and found
      evidence of oxidant stress as indicated by decreases in the activities of the
      renal antioxidant enzymes, superoxide dismutase, catalase, and glutathione
      peroxidase, with increased kidney cell apoptosis and serum malondialdehyde
      levels, all evident by 21 days of EG treatment. These effects of hyperoxaluria
      were reversed by concurrent PGG treatment along with decreased urinary oxalate
      levels and CaOx supersaturation. Renal epithelial cell expression of the crystal
      binding molecule hyaluronan increased diffusely within 7 days of EG initiation,
      suggesting it is not a result of but precedes crystal deposition. Renal cell
      osteopontin (OPN) was also upregulated in EG-treated animals, and PGG
      significantly attenuated overexpression of both OPN and hyaluronan. Thus, our
      findings demonstrate that PGG reduces renal crystallization and oxidative renal
      cell injury, and may be a candidate chemopreventive agent for nephrolithiasis.

PMID- 21085115
TI  - Developing treatments for female sexual dysfunction.
AB  - Female sexual dysfunction (FSD) is a term that encompasses a collection of sexual
      disorders that can affect women throughout their adult life. FSD has multiple
      causes, with physiological,psychological, and social determinants.1 The
      complexity of the female sexual response with overlapping subjective and
      physiological components and the potential presence of sexual comorbidities
      present unique challenges for the design and conduct of randomized, controlled
      clinical studies.

PMID- 21085116
TI  - Dapoxetine for premature ejaculation.
AB  - Premature ejaculation (PE) is the most common form of male sexual dysfunction,
      with an estimated worldwide prevalence of 20-30%.1 Although PE is not life
      threatening, it has significant impact on quality of life. The fourth edition of
      the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)defines PE
      as "persistent or recurrent ejaculation with minimal sexual stimulation before,
      on, or shortly after penetration and before the person wishes it" that "causes
      marked distress or interpersonal difficulty" and "is not due exclusively to the
      direct effects of a substance."2 The International Society for Sexual Medicine,
      which recently modified the definition to include the threshold ejaculatory
      latency time, defines PEas "male sexual dysfunction characterized by ejaculation
      which always or nearly always occurs prior to or within 1 min of vaginal
      penetration; the inability to delay ejaculation on all or nearly all vaginal
      penetrations; and negative personal consequences such as distress, bother,
      frustration, and/or the avoidance of sexual intimacy."3 The lack of ejaculatory
      control is consistent among all clinical definitions of PE and is a highly
      sensitive predictor of the condition.

PMID- 21085111
TI  - White matter changes in healthy adolescents at familial risk for unipolar
      depression: a diffusion tensor imaging study.
AB  - Alterations in white matter integrity of several cortical and subcortical
      circuits have been reported in relation to unipolar major depressive disorder. It
      is not clear whether these white matter changes precede the onset of illness. In
      all, 13 adolescent volunteers with no personal or family history of a psychiatric
      disorder (controls) and 18 adolescent volunteers with no personal history of a
      psychiatric illness including depression, but who were at high risk for
      developing unipolar depression by virtue of parental depression (high-risk
      youth), underwent diffusion tensor imaging studies. An automated tract-based
      spatial statistics method, a whole-brain voxel-by-voxel analysis, was used to
      analyze the scans. Population average diffusion parameter values were also
      calculated for each tract. Adolescents at high risk for unipolar depression had
      lower fractional anisotropy (FA) values in the left cingulum, splenium of the
      corpus callosum, superior longitudinal fasciculi, uncinate, and inferior fronto
      occipital fasciculi than did controls. Altered white matter integrity in healthy
      adolescents at familial risk for unipolar depression suggests that it might serve
      as a vulnerability marker for the illness.

PMID- 21085117
TI  - Cap binding and immune evasion revealed by Lassa nucleoprotein structure.
AB  - Lassa virus, the causative agent of Lassa fever, causes thousands of deaths
      annually and is a biological threat agent, for which there is no vaccine and
      limited therapy. The nucleoprotein (NP) of Lassa virus has essential roles in
      viral RNA synthesis and immune suppression, the molecular mechanisms of which are
      poorly understood. Here we report the crystal structure of Lassa virus NP at 1.80
      A resolution, which reveals amino (N)- and carboxy (C)-terminal domains with
      structures unlike any of the reported viral NPs. The N domain folds into a novel
      structure with a deep cavity for binding the m7GpppN cap structure that is
      required for viral RNA transcription, whereas the C domain contains 3'-5'
      exoribonuclease activity involved in suppressing interferon induction. To our
      knowledge this is the first X-ray crystal structure solved for an arenaviral NP,
      which reveals its unexpected functions and indicates unique mechanisms in cap
      binding and immune evasion. These findings provide great potential for vaccine
      and drug development.

PMID- 21085118
TI  - Trapped antihydrogen.
AB  - Antimatter was first predicted in 1931, by Dirac. Work with high-energy
      antiparticles is now commonplace, and anti-electrons are used regularly in the
      medical technique of positron emission tomography scanning. Antihydrogen, the
      bound state of an antiproton and a positron, has been produced at low energies at
      CERN (the European Organization for Nuclear Research) since 2002. Antihydrogen is
      of interest for use in a precision test of nature's fundamental symmetries. The
      charge conjugation/parity/time reversal (CPT) theorem, a crucial part of the
      foundation of the standard model of elementary particles and interactions,
      demands that hydrogen and antihydrogen have the same spectrum. Given the current
      experimental precision of measurements on the hydrogen atom (about two parts in
      10(14) for the frequency of the 1s-to-2s transition), subjecting antihydrogen to
      rigorous spectroscopic examination would constitute a compelling, model
      independent test of CPT. Antihydrogen could also be used to study the
      gravitational behaviour of antimatter. However, so far experiments have produced
      antihydrogen that is not confined, precluding detailed study of its structure.
      Here we demonstrate trapping of antihydrogen atoms. From the interaction of about
      10(7) antiprotons and 7 * 10(8) positrons, we observed 38 annihilation events
      consistent with the controlled release of trapped antihydrogen from our magnetic
      trap; the measured background is 1.4 +/- 1.4 events. This result opens the door
      to precision measurements on anti-atoms, which can soon be subjected to the same
      techniques as developed for hydrogen.

PMID- 21085119
TI  - Acid sensing by the Drosophila olfactory system.
AB  - The odour of acids has a distinct quality that is perceived as sharp, pungent and
      often irritating. How acidity is sensed and translated into an appropriate
      behavioural response is poorly understood. Here we describe a functionally
      segregated population of olfactory sensory neurons in the fruitfly, Drosophila
      melanogaster, that are highly selective for acidity. These olfactory sensory
      neurons express IR64a, a member of the recently identified ionotropic receptor
      (IR) family of putative olfactory receptors. In vivo calcium imaging showed that
      IR64a+ neurons projecting to the DC4 glomerulus in the antennal lobe are
      specifically activated by acids. Flies in which the function of IR64a+ neurons or
      the IR64a gene is disrupted had defects in acid-evoked physiological and
      behavioural responses, but their responses to non-acidic odorants remained
      unaffected. Furthermore, artificial stimulation of IR64a+ neurons elicited
      avoidance responses. Taken together, these results identify cellular and
      molecular substrates for acid detection in the Drosophila olfactory system and
      support a labelled-line mode of acidity coding at the periphery.

PMID- 21085120
TI  - Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs.
AB  - Post-transcriptional gene regulation frequently occurs through elements in mRNA
      3' untranslated regions (UTRs). Although crucial roles for 3'UTR-mediated gene
      regulation have been found in Caenorhabditis elegans, most C. elegans genes have
      lacked annotated 3'UTRs. Here we describe a high-throughput method for reliable
      identification of polyadenylated RNA termini, and we apply this method, called
      poly(A)-position profiling by sequencing (3P-Seq), to determine C. elegans
      3'UTRs. Compared to standard methods also recently applied to C. elegans UTRs, 3P
      Seq identified 8,580 additional UTRs while excluding thousands of shorter UTR
      isoforms that do not seem to be authentic. Analysis of this expanded and
      corrected data set suggested that the high A/U content of C. elegans 3'UTRs
      facilitated genome compaction, because the elements specifying cleavage and
      polyadenylation, which are A/U rich, can more readily emerge in A/U-rich regions.
      Indeed, 30% of the protein-coding genes have mRNAs with alternative, partially
      overlapping end regions that generate another 10,480 cleavage and polyadenylation
      sites that had gone largely unnoticed and represent potential evolutionary
      intermediates of progressive UTR shortening. Moreover, a third of the
      convergently transcribed genes use palindromic arrangements of bidirectional
      elements to specify UTRs with convergent overlap, which also contributes to
      genome compaction by eliminating regions between genes. Although nematode 3'UTRs
      have median length only one-sixth that of mammalian 3'UTRs, they have twice the
      density of conserved microRNA sites, in part because additional types of seed
      complementary sites are preferentially conserved. These findings reveal the
      influence of cleavage and polyadenylation on the evolution of genome architecture
      and provide resources for studying post-transcriptional gene regulation.

PMID- 21085122
TI  - Data quality control in genetic case-control association studies.
AB  - This protocol details the steps for data quality assessment and control that are
      typically carried out during case-control association studies. The steps
      described involve the identification and removal of DNA samples and markers that
      introduce bias. These critical steps are paramount to the success of a case
      control study and are necessary before statistically testing for association. We
      describe how to use PLINK, a tool for handling SNP data, to perform assessments
      of failure rate per individual and per SNP and to assess the degree of
      relatedness between individuals. We also detail other quality-control procedures,
      including the use of SMARTPCA software for the identification of ancestral
      outliers. These platforms were selected because they are user-friendly, widely
      used and computationally efficient. Steps needed to detect and establish a
      disease association using case-control data are not discussed here. Issues
      concerning study design and marker selection in case-control studies have been
      discussed in our earlier protocols. This protocol, which is routinely used in our
      labs, should take approximately 8 h to complete.

PMID- 21085123
TI  - Simultaneous analysis of relative protein expression levels across multiple
      samples using iTRAQ isobaric tags with 2D nano LC-MS/MS.
AB  - In this paper, we describe the use of iTRAQ (isobaric Tags for Relative and
      Absolute Quantitation) tags for comparison of protein expression levels between
      multiple samples. These tags label all peptides in a protein digest before
      labeled samples are pooled, fractionated and analyzed using mass spectrometry
      (MS). As the tags are isobaric, the intensity of each peak is the sum of the
      intensity of this peptide from all samples, providing a moderate enhancement in
      sensitivity. On peptide fragmentation, amino-acid sequence ions also show this
      summed intensity, providing a sensitivity enhancement. However, the distinct
      distribution of isotopes in the tags is such that, on further fragmentation, a
      tag-specific reporter ion is released. The relative intensities of these ions
      represent the relative amount of peptide in the analytes. Integration of the
      relative quantification data for the peptides allows relative quantification of
      the protein. This protocol discusses the rationale behind design, optimization
      and performance of experiments, comparing protein samples using iTRAQ chemistries
      combined with strong cation exchange chromatographic fractionation and MS.

PMID- 21085121
TI  - Quantitative reactivity profiling predicts functional cysteines in proteomes.
AB  - Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its
      reactivity is tuned to perform diverse biochemical functions. The absence of a
      consensus sequence that defines functional cysteines in proteins has hindered
      their discovery and characterization. Here we describe a proteomics method to
      profile quantitatively the intrinsic reactivity of cysteine residues en masse
      directly in native biological systems. Hyper-reactivity was a rare feature among
      cysteines and it was found to specify a wide range of activities, including
      nucleophilic and reductive catalysis and sites of oxidative modification. Hyper
      reactive cysteines were identified in several proteins of uncharacterized
      function, including a residue conserved across eukaryotic phylogeny that we show
      is required for yeast viability and is involved in iron-sulphur protein
      biogenesis. We also demonstrate that quantitative reactivity profiling can form
      the basis for screening and functional assignment of cysteines in computationally
      designed proteins, where it discriminated catalytically active from inactive
      cysteine hydrolase designs.

PMID- 21085124
TI  - Generation of acetyllysine antibodies and affinity enrichment of acetylated
      peptides.
AB  - Lysine acetylation has emerged as one of the major post-translational
      modifications, as indicated by its roles in chromatin remodeling, activation of
      transcription factors and, most recently, regulation of metabolic enzymes.
      Identification of acetylation sites in a protein is the first essential step for
      functional characterization of acetylation in physiological regulation. However,
      the study of the acetylome is hindered by the lack of suitable physical and
      biochemical properties of the acetyl group and existence of high-abundance
      acetylated histones in the cell, and needs a robust method to overcome these
      problems. Here we present protocols for (i) using chemically acetylated ovalbumin
      and synthetic acetylated peptide to generate a pan-acetyllysine antibody and a
      site-specific antibody to Lys288-acetylated argininosuccinate lyase,
      respectively; (ii) using subcellular fractionation to reduce highly abundant
      acetylated histones; and (iii) using acetyllysine antibody affinity purification
      and mass spectrometry to characterize acetylome of human liver tissue. The entire
      characterization procedure takes ~2-3 d to complete.

PMID- 21085126
TI  - SNPs in axon guidance pathway genes and susceptibility for Parkinson's disease in
      the Korean population.
AB  - Single-nucleotide polymorphisms (SNPs) in genes of the axon guidance pathway have
      been reported to be a possible susceptibility factor for Parkinson's disease
      (PD). This study investigated whether the genetic variability in the axon
      guidance pathway is a susceptibility factor in PD patients in the Korean
      population. A total of 373 patients and 384 healthy subjects were included. A set
      of 22 SNPs was analyzed, and the risk of PD was evaluated using odds ratios in an
      unconditional and conditional logistic regression models of age- and gender
      matched subsets. A multidimensionality reduction (MDR) analysis was performed to
      explore potential gene-gene interactions. SNPs in the DCC, CHP, RRAS2 and EPHB1
      genes of the axon guidance pathway showed significant associations with PD. The
      DCC rs17468382 and EPHB1 rs2030737 SNPs may be associated with increased PD risk,
      and the CHP rs6492998 and RRAS2 rs2970332 SNPs may be associated with reduced PD
      risk. However, no significant interactions for PD risk were found in the MDR
      analysis and logistic regression analysis using SNP interaction terms. This study
      supports that only four of the selected 22 SNPs are regulating factors associated
      with PD in the Korean population. However, no interactions were found among the
      SNPs, suggesting that the effect for the pathway as a whole is not greater than
      that for single genes in the Korean population. Further investigations involving
      populations of various ethnicities and other genetic markers and models are
      warranted.

PMID- 21085125
TI  - Measurement of telomere length by the Southern blot analysis of terminal
      restriction fragment lengths.
AB  - In this protocol we describe a method to obtain telomere length parameters using
      Southern blots of terminal restriction fragments (TRFs). We use this approach
      primarily for epidemiological studies that examine leukocyte telomere length.
      However, the method can be adapted for telomere length measurements in other
      cells whose telomere lengths are within its detection boundaries. After
      extraction, DNA is inspected for integrity, digested, resolved by gel
      electrophoresis, transferred to a membrane, hybridized with labeled probes and
      exposed to X-ray film using chemiluminescence. Although precise and highly
      accurate, the method requires a considerable amount of DNA (3 MUg per sample) and
      it measures both the canonical and noncanonical components of telomeres. The
      method also provides parameters of telomere length distribution in each DNA
      sample, which are useful in answering questions beyond those focusing on the mean
      length of telomeres in a given sample. A skilled technician can measure TRF
      length in ~130 samples per week.

PMID- 21085127
TI  - A new c.1621 C > G, p.R541G lamin A/C mutation in a family with DCM and regional
      wall motion abnormalities (akinesis/dyskinesis): genotype-phenotype correlation.
AB  - Mutations in the lamin A/C gene (LMNA) are established causes of familial dilated
      cardiomyopathy (DCM) with atrio-ventricular block although relatively little is
      known about genotype-phenotype correlations. We describe a 23-year-old patient
      who presented with inferolateral wall thinning and akinesis with evidence of mid
      myocardial fibrosis on cardiac magnetic resonance. Molecular analysis driven by
      clinical similarities with a previously described case harboring the p.R541C LMNA
      mutation revealed a novel c.1621 C > G, p.R541G substitution whose pathogenicity
      was confirmed by transfection of mouse myoblasts. Our results emphasize the role
      of LMNA mutations at position R541 in DCM cases with segmental LV wall motion
      akinesis/dyskinesis.

PMID- 21085128
TI  - Closing the climategate.

PMID- 21085129
TI  - Scope for change.

PMID- 21085130
TI  - Scientists wanted.

PMID- 21085142
TI  - Scope sails into budget void.

PMID- 21085143
TI  - Good news for 'good' cholesterol.

PMID- 21085144
TI  - Antimatter held for questioning.

PMID- 21085145
TI  - Study says middle sized labs do best.

PMID- 21085146
TI  - UK science will be judged on impact.

PMID- 21085147
TI  - Germany plans for healthy future.

PMID- 21085149
TI  - No rest for the bio-wikis.

PMID- 21085150
TI  - Climate: The hottest year.

PMID- 21085151
TI  - Science communication: Scientist as star.

PMID- 21085152
TI  - The end of cheap coal.

PMID- 21085153
TI  - Questioning economic growth.

PMID- 21085160
TI  - European bounty for taxonomists.

PMID- 21085161
TI  - Reef technology to rescue Venice.

PMID- 21085162
TI  - Misreporting: a glowing report.

PMID- 21085163
TI  - Innovation in Europe - three questions.

PMID- 21085164
TI  - Benoit Mandelbrot (1924-2010).

PMID- 21085166
TI  - Spectroscopy: Clear signals from surfaces.

PMID- 21085165
TI  - Chemical biology: Synthetic metabolism goes green.

PMID- 21085168
TI  - Neuroscience: Excessive mobility interrupted.

PMID- 21085169
TI  - Quantum physics: entangled quartet.

PMID- 21085170
TI  - Fisheries: Measuring biodiversity in marine ecosystems.

PMID- 21085172
TI  - Materials chemistry: Thin films with a hidden twist.

PMID- 21085171
TI  - Reproductive ageing: Of worms and women.

PMID- 21085174
TI  - The moment of truth for WIMP dark matter.
AB  - We know that dark matter constitutes 85 per cent of all the matter in the
      Universe, but we do not know of what it is made. Amongst the many dark matter
      candidates proposed, WIMPs (weakly interacting massive particles) occupy a
      special place, because they arise naturally from new theories that seek to extend
      the standard model of particle physics. With the advent of the Large Hadron
      Collider at CERN, and a new generation of astroparticle experiments, the moment
      of truth has come for WIMPs: either we will discover them in the next five to ten
      years, or we will witness their inevitable decline.

PMID- 21085175
TI  - Entanglement of spin waves among four quantum memories.
AB  - Quantum networks are composed of quantum nodes that interact coherently through
      quantum channels, and open a broad frontier of scientific opportunities. For
      example, a quantum network can serve as a 'web' for connecting quantum processors
      for computation and communication, or as a 'simulator' allowing investigations of
      quantum critical phenomena arising from interactions among the nodes mediated by
      the channels. The physical realization of quantum networks generically requires
      dynamical systems capable of generating and storing entangled states among
      multiple quantum memories, and efficiently transferring stored entanglement into
      quantum channels for distribution across the network. Although such capabilities
      have been demonstrated for diverse bipartite systems, entangled states have not
      been achieved for interconnects capable of 'mapping' multipartite entanglement
      stored in quantum memories to quantum channels. Here we demonstrate measurement
      induced entanglement stored in four atomic memories; user-controlled, coherent
      transfer of the atomic entanglement to four photonic channels; and
      characterization of the full quadripartite entanglement using quantum uncertainty
      relations. Our work therefore constitutes an advance in the distribution of
      multipartite entanglement across quantum networks. We also show that our
      entanglement verification method is suitable for studying the entanglement order
      of condensed-matter systems in thermal equilibrium.

PMID- 21085176
TI  - Free-standing mesoporous silica films with tunable chiral nematic structures.
AB  - Chirality at the molecular level is found in diverse biological structures, such
      as polysaccharides, proteins and DNA, and is responsible for many of their unique
      properties. Introducing chirality into porous inorganic solids may produce new
      types of materials that could be useful for chiral separation, stereospecific
      catalysis, chiral recognition (sensing) and photonic materials. Template
      synthesis of inorganic solids using the self-assembly of lyotropic liquid
      crystals offers access to materials with well-defined porous structures, but only
      recently has chirality been introduced into hexagonal mesostructures through the
      use of a chiral surfactant. Efforts to impart chirality at a larger length scale
      using self-assembly are almost unknown. Here we describe the development of a
      photonic mesoporous inorganic solid that is a cast of a chiral nematic liquid
      crystal formed from nanocrystalline cellulose. These materials may be obtained as
      free-standing films with high surface area. The peak reflected wavelength of the
      films can be varied across the entire visible spectrum and into the near-infrared
      through simple changes in the synthetic conditions. To the best of our knowledge
      these are the first materials to combine mesoporosity with long-range chiral
      ordering that produces photonic properties. Our findings could lead to the
      development of new materials for applications in, for example, tuneable
      reflective filters and sensors. In addition, this type of material could be used
      as a hard template to generate other new materials with chiral nematic
      structures.

PMID- 21085177
TI  - Intrusion triggering of the 2010 Eyjafjallajokull explosive eruption.
AB  - Gradual inflation of magma chambers often precedes eruptions at highly active
      volcanoes. During such eruptions, rapid deflation occurs as magma flows out and
      pressure is reduced. Less is known about the deformation style at moderately
      active volcanoes, such as Eyjafjallajokull, Iceland, where an explosive summit
      eruption of trachyandesite beginning on 14 April 2010 caused exceptional
      disruption to air traffic, closing airspace over much of Europe for days. This
      eruption was preceded by an effusive flank eruption of basalt from 20 March to 12
      April 2010. The 2010 eruptions are the culmination of 18 years of intermittent
      volcanic unrest. Here we show that deformation associated with the eruptions was
      unusual because it did not relate to pressure changes within a single magma
      chamber. Deformation was rapid before the first eruption (>5 mm per day after 4
      March), but negligible during it. Lack of distinct co-eruptive deflation
      indicates that the net volume of magma drained from shallow depth during this
      eruption was small; rather, magma flowed from considerable depth. Before the
      eruption, a ~0.05 km(3) magmatic intrusion grew over a period of three months, in
      a temporally and spatially complex manner, as revealed by GPS (Global Positioning
      System) geodetic measurements and interferometric analysis of satellite radar
      images. The second eruption occurred within the ice-capped caldera of the
      volcano, with explosivity amplified by magma-ice interaction. Gradual contraction
      of a source, distinct from the pre-eruptive inflation sources, is evident from
      geodetic data. Eyjafjallajokull's behaviour can be attributed to its off-rift
      setting with a 'cold' subsurface structure and limited magma at shallow depth, as
      may be typical for moderately active volcanoes. Clear signs of volcanic unrest
      signals over years to weeks may indicate reawakening of such volcanoes, whereas
      immediate short-term eruption precursors may be subtle and difficult to detect.

PMID- 21085178
TI  - The trophic fingerprint of marine fisheries.
AB  - Biodiversity indicators provide a vital window on the state of the planet,
      guiding policy development and management. The most widely adopted marine
      indicator is mean trophic level (MTL) from catches, intended to detect shifts
      from high-trophic-level predators to low-trophic-level invertebrates and plankton
      feeders. This indicator underpins reported trends in human impacts, declining
      when predators collapse ("fishing down marine food webs") and when low-trophic
      level fisheries expand ("fishing through marine food webs"). The assumption is
      that catch MTL measures changes in ecosystem MTL and biodiversity. Here we
      combine model predictions with global assessments of MTL from catches, trawl
      surveys and fisheries stock assessments and find that catch MTL does not reliably
      predict changes in marine ecosystems. Instead, catch MTL trends often diverge
      from ecosystem MTL trends obtained from surveys and assessments. In contrast to
      previous findings of rapid declines in catch MTL, we observe recent increases in
      catch, survey and assessment MTL. However, catches from most trophic levels are
      rising, which can intensify fishery collapses even when MTL trends are stable or
      increasing. To detect fishing impacts on marine biodiversity, we recommend
      greater efforts to measure true abundance trends for marine species, especially
      those most vulnerable to fishing.

PMID- 21085179
TI  - A widespread family of polymorphic contact-dependent toxin delivery systems in
      bacteria.
AB  - Bacteria have developed mechanisms to communicate and compete with one another in
      diverse environments. A new form of intercellular communication, contact
      dependent growth inhibition (CDI), was discovered recently in Escherichia coli.
      CDI is mediated by the CdiB/CdiA two-partner secretion (TPS) system. CdiB
      facilitates secretion of the CdiA 'exoprotein' onto the cell surface. An
      additional small immunity protein (CdiI) protects CDI(+) cells from
      autoinhibition. The mechanisms by which CDI blocks cell growth and by which CdiI
      counteracts this growth arrest are unknown. Moreover, the existence of CDI
      activity in other bacteria has not been explored. Here we show that the CDI
      growth inhibitory activity resides within the carboxy-terminal region of CdiA
      (CdiA-CT), and that CdiI binds and inactivates cognate CdiA-CT, but not
      heterologous CdiA-CT. Bioinformatic and experimental analyses show that multiple
      bacterial species encode functional CDI systems with high sequence variability in
      the CdiA-CT and CdiI coding regions. CdiA-CT heterogeneity implies that a range
      of toxic activities are used during CDI. Indeed, CdiA-CTs from uropathogenic E.
      coli and the plant pathogen Dickeya dadantii have different nuclease activities,
      each providing a distinct mechanism of growth inhibition. Finally, we show that
      bacteria lacking the CdiA-CT and CdiI coding regions are unable to compete with
      isogenic wild-type CDI(+) cells both in laboratory media and on a eukaryotic
      host. Taken together, these results suggest that CDI systems constitute an
      intricate immunity network with an important function in bacterial competition.

PMID- 21085180
TI  - L1 retrotransposition in neurons is modulated by MeCP2.
AB  - Long interspersed nuclear elements-1 (LINE-1 or L1s) are abundant
      retrotransposons that comprise approximately 20% of mammalian genomes. Active L1
      retrotransposons can impact the genome in a variety of ways, creating insertions,
      deletions, new splice sites or gene expression fine-tuning. We have shown
      previously that L1 retrotransposons are capable of mobilization in neuronal
      progenitor cells from rodents and humans and evidence of massive L1 insertions
      was observed in adult brain tissues but not in other somatic tissues. In
      addition, L1 mobility in the adult hippocampus can be influenced by the
      environment. The neuronal specificity of somatic L1 retrotransposition in neural
      progenitors is partially due to the transition of a Sox2/HDAC1 repressor complex
      to a Wnt-mediated T-cell factor/lymphoid enhancer factor (TCF/LEF)
      transcriptional activator. The transcriptional switch accompanies chromatin
      remodelling during neuronal differentiation, allowing a transient stimulation of
      L1 transcription. The activity of L1 retrotransposons during brain development
      can have an impact on gene expression and neuronal function, thereby increasing
      brain-specific genetic mosaicism. Further understanding of the molecular
      mechanisms that regulate L1 expression should provide new insights into the role
      of L1 retrotransposition during brain development. Here we show that L1 neuronal
      transcription and retrotransposition in rodents are increased in the absence of
      methyl-CpG-binding protein 2 (MeCP2), a protein involved in global DNA
      methylation and human neurodevelopmental diseases. Using neuronal progenitor
      cells derived from human induced pluripotent stem cells and human tissues, we
      revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have
      increased susceptibility for L1 retrotransposition. Our data demonstrate that L1
      retrotransposition can be controlled in a tissue-specific manner and that disease
      related genetic mutations can influence the frequency of neuronal L1
      retrotransposition. Our findings add a new level of complexity to the molecular
      events that can lead to neurological disorders.

PMID- 21085182
TI  - Molecular coupling of Tsix regulation and pluripotency.
AB  - The reprogramming of X-chromosome inactivation during the acquisition of
      pluripotency in vivo and in vitro is accompanied by the repression of Xist, the
      trigger of X-inactivation, and the upregulation of its antisense counterpart
      Tsix. We have shown that key factors supporting pluripotency-Nanog, Oct4 and Sox2
      bind within Xist intron 1 in undifferentiated embryonic stem cells (ESC) to
      repress Xist transcription. However, the relationship between transcription
      factors of the pluripotency network and Tsix regulation has remained unclear.
      Here we show that Tsix upregulation in embryonic stem cells depends on the
      recruitment of the pluripotent marker Rex1, and of the reprogramming-associated
      factors Klf4 and c-Myc, by the DXPas34 minisatellite associated with the Tsix
      promoter. Upon deletion of DXPas34, binding of the three factors is abrogated and
      the transcriptional machinery is no longer efficiently recruited to the Tsix
      promoter. Additional analyses including knockdown experiments further demonstrate
      that Rex1 is critically important for efficient transcription elongation of Tsix.
      Hence, distinct embryonic-stem-cell-specific complexes couple X-inactivation
      reprogramming and pluripotency, with Nanog, Oct4 and Sox2 repressing Xist to
      facilitate the reactivation of the inactive X, and Klf4, c-Myc and Rex1
      activating Tsix to remodel Xist chromatin and ensure random X-inactivation upon
      differentiation. The holistic pattern of Xist/Tsix regulation by pluripotent
      factors that we have identified suggests a general direct governance of complex
      epigenetic processes by the machinery dedicated to pluripotency.

PMID- 21085181
TI  - 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family
      members.
AB  - Cellular messenger RNA (mRNA) of higher eukaryotes and many viral RNAs are
      methylated at the N-7 and 2'-O positions of the 5' guanosine cap by specific
      nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7
      methylation is essential for RNA translation and stability, the function of 2'-O
      methylation has remained uncertain since its discovery 35 years ago. Here we show
      that a West Nile virus (WNV) mutant (E218A) that lacks 2'-O MTase activity was
      attenuated in wild-type primary cells and mice but was pathogenic in the absence
      of type I interferon (IFN) signalling. 2'-O methylation of viral RNA did not
      affect IFN induction in WNV-infected fibroblasts but instead modulated the
      antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT),
      which are interferon-stimulated genes (ISGs) implicated in regulation of protein
      translation. Poxvirus and coronavirus mutants that lacked 2'-O MTase activity
      similarly showed enhanced sensitivity to the antiviral actions of IFN and,
      specifically, IFIT proteins. Our results demonstrate that the 2'-O methylation of
      the 5' cap of viral RNA functions to subvert innate host antiviral responses
      through escape of IFIT-mediated suppression, and suggest an evolutionary
      explanation for 2'-O methylation of cellular mRNA: to distinguish self from non
      self RNA. Differential methylation of cytoplasmic RNA probably serves as an
      example for pattern recognition and restriction of propagation of foreign viral
      RNA in host cells.

PMID- 21085185
TI  - Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for
      key inflammatory pathogenic circuits in psoriasis.
AB  - Psoriasis is a complex inflammatory disease mediated by tumor necrosis factor
      (TNF)-alpha and cytokines secreted by specialized T-cell populations, e.g., IL
      17, IL-22, and IFN-gamma. The mechanisms by which innate and adaptive immune
      cytokines regulate inflammation in psoriasis are not completely understood. We
      sought to investigate the effects of TNF-alpha and IL-17 on keratinocyte (KC)
      gene profile, to identify genes that might be coregulated by these cytokines and
      determine how synergistically activated genes relate to the psoriasis
      transcriptome. Primary KCs were stimulated with IL-17 or TNF-alpha alone, or in
      combination. KC responses were assessed by gene array analysis, followed by
      reverse transcriptase-PCR confirmation for significant genes. We identified 160
      genes that were synergistically upregulated by IL-17 and TNF-alpha, and 196 genes
      in which the two cytokines had at least an additive effect. Synergistically
      upregulated genes included some of the highest expressed genes in psoriatic skin
      with an impressive correlation between IL-17/TNF-alpha-induced genes and the
      psoriasis gene signature. KCs may be key drivers of pathogenic inflammation in
      psoriasis through integrating responses to TNF-alpha and IL-17. Our data predict
      that psoriasis therapy with either TNF or IL-17 antagonists will produce greater
      modulation of the synergistic/additive gene set, which consists of the most
      highly expressed genes in psoriasis skin lesions.

PMID- 21085184
TI  - Experimental priapism is associated with increased oxidative stress and
      activation of protein degradation pathways in corporal tissue.
AB  - Priapism is a debilitating disease for which there is at present no clinically
      accepted pharmacological intervention. It has been estimated that priapism
      lasting more than 24 h in patients is associated with a 44-90% rate of ED. In
      this investigation, we determined in two animal models of priapism (opiorphin
      induced priapism in the rat and priapism in a mouse model of sickle cell disease)
      if there is evidence for an increase in markers of oxidative stress in corporal
      tissue. In both animal models, we demonstrate that priapism results in increased
      levels of lipid peroxidation, glutathione S-transferase activity and oxidatively
      damaged proteins in corporal tissue. Using western blot analysis, we demonstrated
      there is upregulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2,
      and the lysosomal autophage protein, LC3. The antiapoptotic protein, Bcl-2, was
      also upregulated. Overall, we demonstrate that priapism is associated with
      increased oxidative stress in corporal tissue and the activation of protein
      degradation pathways. As oxidative stress is known to mediate the development of
      ED resulting from several etiologies (for example, ED resulting from diabetes and
      aging), we suggest that damage to erectile tissue resulting from priapism might
      be prevented by treatments targeting oxidative stress.

PMID- 21085186
TI  - Nerve growth factor partially recovers inflamed skin from stress-induced
      worsening in allergic inflammation.
AB  - Neuroimmune dysregulation characterizes atopic disease, but its nature and
      clinical impact remain ill-defined. Induced by stress, the neurotrophin nerve
      growth factor (NGF) may worsen cutaneous inflammation. We therefore studied the
      role of NGF in the cutaneous stress response in a mouse model for atopic
      dermatitis-like allergic dermatitis (AlD). Combining several methods, we found
      that stress increased cutaneous but not serum or hypothalamic NGF in telogen
      mice. Microarray analysis showed increased mRNAs of inflammatory and growth
      factors associated with NGF in the skin. In stress-worsened AlD, NGF-neutralizing
      antibodies markedly reduced epidermal thickening together with NGF, neurotrophin
      receptor (tyrosine kinase A and p75 neurotrophin receptor), and transforming
      growth factor-beta expression by keratinocytes but did not alter transepidermal
      water loss. Moreover, NGF expression by mast cells was reduced; this corresponded
      to reduced cutaneous tumor necrosis factor-alpha (TNF-alpha) mRNA levels but not
      to changes in mast cell degranulation or in the T helper type 1 (Th1)/Th2
      cytokine balance. Also, eosinophils expressed TNF receptor type 2, and we
      observed reduced eosinophil infiltration after treatment with NGF-neutralizing
      antibodies. We thus conclude that NGF acts as a local stress mediator in
      perceived stress and allergy and that increased NGF message contributes to
      worsening of cutaneous inflammation mainly by enhancing epidermal hyperplasia,
      pro-allergic cytokine induction, and allergy-characteristic cellular
      infiltration.

PMID- 21085189
TI  - The relationship between neurological disease and bullous pemphigoid: a
      population-based case-control study.
AB  - Previous small studies and case reports have suggested that neurological
      disorders may be associated with bullous pemphigoid (BP). The objective of this
      study was to assess BP risk in patients with neurological diseases. Computerized
      medical records from the Health Improvement Network, a large population-based UK
      general practice database, were used to conduct a matched case-control analysis.
      Conditional logistic regression was used to calculate odds ratios for specified
      neurological disorders. Comparing cases (n=868) to controls (n=3,453), stroke was
      seen in 8 vs. 5%, odds ratio (OR) 1.8 (1.3-2.5); dementia in 7 vs. 2%, OR 3.4
      (2.4-4.8); Parkinson's disease in 3 vs. 1%, OR 3.0 (1.8-5.0); epilepsy in 2 vs.
      1%, OR 1.7 (1.0-3.0); and multiple sclerosis in 1 vs 0.1% (OR 10.7 (2.8-40.2).
      Estimates were not altered greatly when diagnoses up to 3 years before BP were
      excluded, except the association with epilepsy was no longer significant.
      Significant associations were only observed where neurological disease was
      diagnosed before the onset of pemphigoid. Study findings, except the association
      with epilepsy, were robust to sensitivity analysis. Strong associations were
      observed between specific neurological diseases and the later development of BP,
      supporting possible causal associations. Mechanisms for disease occurrence based
      on these findings include immobility or age-related autoimmunity.

PMID- 21085190
TI  - Vitiligo autoantigen VIT75 is identified as lamin A in vitiligo by serological
      proteome analysis based on mass spectrometry.
AB  - VIT75 is a 75-kDa melanocyte membrane antigen (Ag) that had been observed, but
      not identified until now. Its immunopathogenic role in vitiligo remains unknown.
      In this study, serological proteome analysis based on mass spectrometry was
      employed to identify VIT75. Three disparate 75-, 60-, and 45-kDa proteins on two
      dimensional (2D) gel were, respectively, identified as lamin A, tyrosinase
      related protein 1, and melanin-concentrating hormone receptor 1. The latter two
      proteins are well-known Ags. Immunoreactivity analysis showed that the 75-kDa
      protein displayed on the 2D gel was recognized by human anti-lamin A IgG.
      Antibody (Ab) reactivity to lamin A was positive in 28.6% of patients' sera. Only
      3.1% healthy sera reacted with the lamin A. A total of 91.7% of the positive sera
      was from the active non-segmental vitiligo (NSV). The positive rate and mean
      titer of anti-lamin A Ab are higher for NSV with autoimmune disease than for NSV
      without autoimmune disease. These data demonstrate that VIT75 is lamin A. To our
      knowledge, this is a previously unreported vitiligo Ag. Anti-lamin A Ab may be a
      potential marker of NSV with autoimmune disease. The study indicates that the
      targets of autoantibodies in vitiligo patients can be revealed by serological
      proteome analysis.

PMID- 21085187
TI  - Comprehensive association analysis of candidate genes for generalized vitiligo
      supports XBP1, FOXP3, and TSLP.
AB  - We previously carried out a genome-wide association study of generalized vitiligo
      (GV) in non-Hispanic whites, identifying 13 confirmed susceptibility loci. In
      this study, we re-analyzed the genome-wide data set (comprising 1,392 cases and
      2,629 controls) to specifically test association of all 33 GV candidate genes
      that have previously been suggested for GV, followed by meta-analysis
      incorporating both current and previously published data. We detected association
      of three of the candidate genes tested: TSLP (rs764916, P=3.0E-04, odds ratio
      (OR)=1.60; meta-P for rs3806933=3.1E-03), XBP1 (rs6005863, P=3.6E-04, OR=1.17;
      meta-P for rs2269577=9.5E-09), and FOXP3 (rs11798415, P=5.8E-04, OR=1.19).
      Association of GV with CTLA4 (rs12992492, P=5.9E-05, OR=1.20; meta-P for
      rs231775=1.0E-04) seems to be secondary to epidemiological association with other
      concomitant autoimmune diseases. Within the major histocompatibility complex
      (MHC), at 6p21.33, association with TAP1-PSMB8 (rs3819721, P=5.2E-06) seems to
      derive from linkage disequilibrium with major primary signals in the MHC class I
      and class II regions.

PMID- 21085188
TI  - Polycomb group proteins are key regulators of keratinocyte function.
AB  - The Polycomb group (PcG) proteins are epigenetic suppressors of gene expression
      that function through modification of histones to change chromatin structure and
      modulate gene expression and cell behavior. Recent studies show that PcG proteins
      are expressed in epidermis, that their levels change during differentiation and
      in disease states, and that PcG expression is regulated by agents that influence
      cell proliferation and survival. The results indicate that PcG proteins regulate
      keratinocyte cell-cycle progression, apoptosis, senescence, and differentiation.
      These proteins are expressed in progenitor cells, in the basal layer, and in
      suprabasal keratinocytes, and the level, timing, and distribution of expression
      suggest that the PcG proteins have a central role in maintaining the balance
      between cell survival and death in multiple epidermal compartments. Additional
      studies indicate an important role in skin cancer progression.

PMID- 21085191
TI  - Staphylococcus aureus hijacks a skin commensal to intensify its virulence:
      immunization targeting beta-hemolysin and CAMP factor.
AB  - The need for a new anti-Staphylococcus aureus therapy that can effectively
      cripple bacterial infection, neutralize secretory virulence factors, and lower
      the risk of creating bacterial resistance is undisputed. Here, we propose what
      is, to our knowledge, a previously unreported infectious mechanism by which S.
      aureus may commandeer Propionibacterium acnes, a key member of the human skin
      microbiome, to spread its invasion and highlight two secretory virulence factors
      (S. aureus beta-hemolysin and P. acnes CAMP (Christie, Atkins, Munch-Peterson)
      factor) as potential molecular targets for immunotherapy against S. aureus
      infection. Our data demonstrate that the hemolysis and cytolysis by S. aureus
      were noticeably augmented when S. aureus was grown with P. acnes. The
      augmentation was significantly abrogated when the P. acnes CAMP factor was
      neutralized or beta-hemolysin of S. aureus was mutated. In addition, the
      hemolysis and cytolysis of recombinant beta-hemolysin were markedly enhanced by
      recombinant CAMP factor. Furthermore, P. acnes exacerbated S. aureus-induced skin
      lesions in vivo. The combination of CAMP factor neutralization and beta-hemolysin
      immunization cooperatively suppressed the skin lesions caused by coinfection of
      P. acnes and S. aureus. These observations suggest a previously unreported
      immunotherapy targeting the interaction of S. aureus with a skin commensal.

PMID- 21085192
TI  - MicroRNA-21 expression in CD4+ T cells is regulated by STAT3 and is
      pathologically involved in Sezary syndrome.
AB  - MicroRNAs (miRNAs) are small RNAs that control gene expression, and are involved
      in the regulation of fundamental biological processes including development, cell
      differentiation, proliferation, and apoptosis. miRNAs regulate gene expression in
      normal hematopoiesis, and aberrant miRNA expression might contribute to
      leukomogenesis. Specifically, miR-21 is abundantly expressed in various tumors
      including leukemia and lymphoma, and is functionally involved in oncogenic
      processes. We investigated a role for miR-21 in Sezary Syndrome (SS), a cutaneous
      T-cell lymphoma (CTCL) with CD4+ tumor cells (Sezary cells) present in the skin,
      lymph nodes, and peripheral blood. It was shown previously that SS is
      characterized by constitutively activated signal transducer and activator of
      transcription 3 (STAT3) signaling. In this study we show by chromatin
      immunoprecipitation that miR-21 is a direct STAT3 target in Sezary cells.
      Stimulation of Sezary cells or healthy CD4+ T cells with the common-gamma chain
      cytokine IL-21 results in a strong activation of STAT3, and subsequent
      upregulation of miR-21 expression. Both pri- and mature miR-21 expression are
      increased in Sezary cells when compared with CD4+ T cells from healthy donors.
      Silencing of miR-21 in Sezary cells results in increased apoptosis, suggesting a
      functional role for miR-21 in the leukomogenic process. Consequently, miR-21
      might represent a therapeutic target for the treatment of SS.

PMID- 21085194
TI  - Refined human artificial chromosome vectors for gene therapy and animal
      transgenesis.
AB  - Human artificial chromosomes (HACs) have several advantages as gene therapy
      vectors, including stable episomal maintenance, and the ability to carry large
      gene inserts. We previously developed HAC vectors from the normal human
      chromosomes using a chromosome engineering technique. However, endogenous genes
      were remained in these HACs, limiting their therapeutic applications. In this
      study, we refined a HAC vector without endogenous genes from human chromosome 21
      in homologous recombination-proficient chicken DT40 cells. The HAC was physically
      characterized using a transformation-associated recombination (TAR) cloning
      strategy followed by sequencing of TAR-bacterial artificial chromosome clones. No
      endogenous genes were remained in the HAC. We demonstrated that any desired gene
      can be cloned into the HAC using the Cre-loxP system in Chinese hamster ovary
      cells, or a homologous recombination system in DT40 cells. The HAC can be
      efficiently transferred to other type of cells including mouse ES cells via
      microcell-mediated chromosome transfer. The transferred HAC was stably maintained
      in vitro and in vivo. Furthermore, tumor cells containing a HAC carrying the
      suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were selectively
      killed by ganciclovir in vitro and in vivo. Thus, this novel HAC vector may be
      useful not only for gene and cell therapy, but also for animal transgenesis.

PMID- 21085193
TI  - A flexible multiplex bead-based assay for detecting germline CDKN2A and CDK4
      variants in melanoma-prone kindreds.
AB  - The presence of recurrent high-risk mutations in cyclin-dependent kinase
      inhibitor 2A/cyclin-dependent kinase 4 (CDKN2A/CDK4) among melanoma-prone
      families suggests that a high-throughput, multiplex assay could serve as an
      effective initial screening tool. To this end, we have developed a multiplex bead
      based assay for high-throughput CDKN2A/CDK4 genotyping in the context of familial
      melanoma. Genomic DNA from 1,603 subjects (1,005 in training set and 598 in
      validation set) were amplified by multiplex PCR using five CDKN2A/CDK4 primer
      sets followed by multiplex allele-specific primer extension for 39 distinct
      germline variants. The products were then sorted and analyzed using the Luminex
      xMAP system. Genotypes were compared with previously determined sequence data. In
      the Toronto training cohort, all 145 samples with known variants were detected by
      the bead assay (100% concordance). Analysis of the 598 samples from the GenoMEL
      validation set led to identification of 150/155 expected variants (96.77%).
      Overall, the bead assay correctly genotyped 1,540/1,603 (96.07%) of all
      individuals in the study and 1,540/1,545 (99.68%) of individuals whose variants
      were represented in the probe set. Out of a total of 62,517 allelic calls, 62,512
      (99.99%) were correctly assigned. The multiplex bead-based assay is an accurate
      method for genotyping CDKN2A/CDK4 variants and is potentially useful in
      genotyping low-to-moderate melanoma risk single-nucleotide polymorphisms.

PMID- 21085195
TI  - Air-assisted intranasal instillation enhances adenoviral delivery to the
      olfactory epithelium and respiratory tract.
AB  - Intranasal instillation is used to deliver adenoviral vectors to the olfactory
      epithelium and respiratory tract. The success of this approach, however, has been
      tempered by inconsistent infectivity in both the epithelium and lungs. Infection
      of the epithelium may be hampered in part by the convoluted structure of the
      cavity, the presence of mucus or poor airflow in the posterior cavity. Delivery
      of adenovirus to the lungs can be uneven in the various lobes and distal
      bronchioles may be poorly infected. Current approaches to circumvent these issues
      rely principally on intubation or intratracheal instillation. Here we describe a
      technique that significantly improves adenoviral infectivity rates without
      requiring surgical intervention. We use compressed air to increase circulation of
      instilled adenovirus, resulting in enhanced infection in both the epithelium and
      lungs. This procedure is straightforward, simple to perform and requires no
      specialized equipment. In the epithelium, neurons and sustentacular cells are
      both labeled. In the lungs, all lobes can be infected, with penetration to the
      most distal bronchioles. The use of compressed air will likely also be useful for
      enhancing the distribution of other, desired agents within the epithelium,
      central nervous system and respiratory tract.

PMID- 21085196
TI  - Pyrosequencing reveals highly diverse and species-specific microbial communities
      in sponges from the Red Sea.
AB  - Marine sponges are associated with a remarkable array of microorganisms. Using a
      tag pyrosequencing technology, this study was the first to investigate in depth
      the microbial communities associated with three Red Sea sponges, Hyrtios erectus,
      Stylissa carteri and Xestospongia testudinaria. We revealed highly diverse sponge
      associated bacterial communities with up to 1000 microbial operational taxonomic
      units (OTUs) and richness estimates of up to 2000 species. Altogether, 26
      bacterial phyla were detected from the Red Sea sponges, 11 of which were absent
      from the surrounding sea water and 4 were recorded in sponges for the first time.
      Up to 100 OTUs with richness estimates of up to 300 archaeal species were
      revealed from a single sponge species. This is by far the highest archaeal
      diversity ever recorded for sponges. A non-negligible proportion of unclassified
      reads was observed in sponges. Our results demonstrated that the sponge
      associated microbial communities remained highly consistent in the same sponge
      species from different locations, although they varied at different degrees among
      different sponge species. A significant proportion of the tag sequences from the
      sponges could be assigned to one of the sponge-specific clusters previously
      defined. In addition, the sponge-associated microbial communities were
      consistently divergent from those present in the surrounding sea water. Our
      results suggest that the Red Sea sponges possess highly sponge-specific or even
      sponge-species-specific microbial communities that are resistant to environmental
      disturbance, and much of their microbial diversity remains to be explored.

PMID- 21085197
TI  - Impact of internal waves on the spatial distribution of Planktothrix rubescens
      (cyanobacteria) in an alpine lake.
AB  - The vertical and horizontal distribution of the cyanobacterium, Planktothrix
      rubescens, was studied in a deep alpine lake (Lac du Bourget) in a 2-year
      monitoring program with 11 sampling points, and a 24-h survey at one sampling
      station. This species is known to proliferate in the metalimnic layer of numerous
      deep mesotrophic lakes in temperate areas, and also to produce hepatotoxins. When
      looking at the distribution of P. rubescens at the scale of the entire lake, we
      found large variations (up to 10  m) in the depth of the biomass peak in the
      water column. These variations were closely correlated to isotherm displacements.
      We also found significant variations in the distribution of the cyanobacterial
      biomass in the northern and southern parts of the lake. We used a physical
      modeling approach to demonstrate that two internal wave modes can explain these
      variations. Internal waves are generated by wind events, but can still be
      detected several days after the end of these events. Finally, our 24-h survey at
      one sampling point demonstrated that the V1H1 sinusoidal motion could evolve into
      nonlinear fronts. All these findings show that internal waves have a major impact
      on the distribution of P. rubescens proliferating in the metalimnic layer of a
      deep lake, and that this process could influence the growth of this species by a
      direct impact on light availability.

PMID- 21085198
TI  - Examining the global distribution of dominant archaeal populations in soil.
AB  - Archaea, primarily Crenarchaeota, are common in soil; however, the structure of
      soil archaeal communities and the factors regulating their diversity and
      abundance remain poorly understood. Here, we used barcoded pyrosequencing to
      comprehensively survey archaeal and bacterial communities in 146 soils,
      representing a multitude of soil and ecosystem types from across the globe.
      Relative archaeal abundance, the percentage of all 16S rRNA gene sequences
      recovered that were archaeal, averaged 2% across all soils and ranged from 0% to
      >10% in individual soils. Soil C:N ratio was the only factor consistently
      correlated with archaeal relative abundances, being higher in soils with lower
      C:N ratios. Soil archaea communities were dominated by just two phylotypes from a
      constrained clade within the Crenarchaeota, which together accounted for >70% of
      all archaeal sequences obtained in the survey. As one of these phylotypes was
      closely related to a previously identified putative ammonia oxidizer, we sampled
      from two long-term nitrogen (N) addition experiments to determine if this taxon
      responds to experimental manipulations of N availability. Contrary to
      expectations, the abundance of this dominant taxon, as well as archaea overall,
      tended to decline with increasing N. This trend was coupled with a concurrent
      increase in known N-oxidizing bacteria, suggesting competitive interactions
      between these groups.

PMID- 21085200
TI  - Human disease: Bound to repeat.

PMID- 21085199
TI  - Metatranscriptomic analysis of ammonia-oxidizing organisms in an estuarine
      bacterioplankton assemblage.
AB  - Quantitative PCR (qPCR) analysis revealed elevated relative abundance (1.8% of
      prokaryotes) of marine group 1 Crenarchaeota (MG1C) in two samples of
      southeastern US coastal bacterioplankton, collected in August 2008, compared with
      samples collected from the same site at different times (mean 0.026%). We
      analyzed the MG1C sequences in metatranscriptomes from these samples to gain an
      insight into the metabolism of MG1C population growing in the environment, and
      for comparison with ammonia-oxidizing bacteria (AOB) in the same samples.
      Assemblies revealed low diversity within sequences assigned to most individual
      MG1C open reading frames (ORFs) and high homology with 'Candidatus Nitrosopumilus
      maritimus' strain SCM1 genome sequences. Reads assigned to ORFs for ammonia
      uptake and oxidation accounted for 37% of all MG1C transcripts. We did not
      recover any reads for Nmar_1354-Nmar_1357, proposed to encode components of an
      alternative, nitroxyl-based ammonia oxidation pathway; however, reads from
      Nmar_1259 and Nmar_1667, annotated as encoding a multicopper oxidase with
      homology to nirK, were abundant. Reads assigned to two homologous ORFs (Nmar_1201
      and Nmar_1547), annotated as hypothetical proteins were also abundant, suggesting
      that their unknown function is important to MG1C. Superoxide dismutase and
      peroxiredoxin-like transcripts were more abundant in the MG1C transcript pool
      than in the complete metatranscriptome, suggesting an enhanced response to
      oxidative stress by the MG1C population. qPCR indicated low AOB abundance
      (0.0010% of prokaryotes), and we found no transcripts related to ammonia
      oxidation and only one RuBisCO transcript among the transcripts assigned to AOB,
      suggesting they were not responding to the same environmental cues as the MG1C
      population.

PMID- 21085201
TI  - Crop genetics: Resequencing sows the seeds.

PMID- 21085202
TI  - Molecular evolution: Concealed connections.

PMID- 21085203
TI  - Analysing biological pathways in genome-wide association studies.
AB  - Genome-wide association (GWA) studies have typically focused on the analysis of
      single markers, which often lacks the power to uncover the relatively small
      effect sizes conferred by most genetic variants. Recently, pathway-based
      approaches have been developed, which use prior biological knowledge on gene
      function to facilitate more powerful analysis of GWA study data sets. These
      approaches typically examine whether a group of related genes in the same
      functional pathway are jointly associated with a trait of interest. Here we
      review the development of pathway-based approaches for GWA studies, discuss their
      practical use and caveats, and suggest that pathway-based approaches may also be
      useful for future GWA studies with sequencing data.

PMID- 21085206
TI  - Numerical evaluation of the Luneburg integral and ray tracing.
AB  - The Luneburg integral has many applications in optics and optoelectronics, among
      which is determination of the refractive-index profile of a Luneburg lens with a
      full or nonfull aperture. Consequently, computationally efficient and accurate
      methods for evaluating this integral represent an important challenge. An
      alternative approach to numerical evaluation of the Luneburg integral that is
      five times faster than existing methods is described. Several improvements in the
      ray-tracing procedure in gradient-index media are also presented. A combination
      of these methods increases the speed of ray tracing through the generalized
      Luneburg lens by as many as 2 orders of magnitude compared with earlier
      algorithms. The precision of our method can be easily controlled.

PMID- 21085204
TI  - Phenomics: the next challenge.
AB  - A key goal of biology is to understand phenotypic characteristics, such as
      health, disease and evolutionary fitness. Phenotypic variation is produced
      through a complex web of interactions between genotype and environment, and such
      a 'genotype-phenotype' map is inaccessible without the detailed phenotypic data
      that allow these interactions to be studied. Despite this need, our ability to
      characterize phenomes - the full set of phenotypes of an individual - lags behind
      our ability to characterize genomes. Phenomics should be recognized and pursued
      as an independent discipline to enable the development and adoption of high
      throughput and high-dimensional phenotyping.

PMID- 21085207
TI  - Test optics error removal.
AB  - Wave-front or surface errors may be divided into rotationally symmetric and
      nonrotationally symmetric terms. It is shown that if either the test part or the
      reference surface in an interferometric test is rotated to N equally spaced
      positions about the optical axis and the resulting wave fronts are averaged, then
      errors in the rotated member with angular orders that are not integer multiples
      of the number of positions will be removed. Thus if the test piece is rotated to
      N equally spaced positions and the data rotated back to a common orientation in
      software, all nonrotationally symmetric errors of the interferometer except those
      of angular order kNtheta are completely removed. It is also shown how this method
      may be applied in an absolute test, giving both rotationally symmetric and
      nonsymmetric components of the surface. A general proof is given that assumes
      only that the surface or wave-front information can be described by some
      arbitrary set of orthognal polynomials in a radial coordinate r and terms in sin
      theta and cos theta. A simulation, using Zernike polynomials, is also presented.

PMID- 21085208
TI  - Modulation-transfer-function-enhanced readout for SPRITE detectors.
AB  - A new readout structure is investigated for signal-processing-in-the-element
      detectors that yields a modulation transfer function that is 3.5 dB better than
      those currently used. Experimental verification is performed in Si rather than
      HgCdTe, with similarity relations derived for the two semiconductors.

PMID- 21085209
TI  - Uniformization of the axial intensity of diffraction axicons by polychromatic
      illumination.
AB  - The axial intensity of axicons illuminated by a coherent wave usually exhibits
      rapid oscillations from diffraction on the sharp edges of the aperture of the
      element. These oscillations can be suppressed when the diffractive version of the
      axicon is illuminated from a polychromatic source. This possibility is examined
      based on the example of the annular-aperture logarithmic axicon. The estimate for
      the wavelength interval of the illuminating source required for uniformization is
      obtained with the help of the stationary-phase method. Furthermore the shape of
      the radial intensity distribution can be maintained almost unchanged. These
      findings are confirmed by numerical evaluation of the Fresnel diffraction
      integral.

PMID- 21085205
TI  - Towards identifying genes underlying ecologically relevant traits in Arabidopsis
      thaliana.
AB  - A major challenge in evolutionary biology and plant breeding is to identify the
      genetic basis of complex quantitative traits, including those that contribute to
      adaptive variation. Here we review the development of new methods and resources
      to fine-map intraspecific genetic variation that underlies natural phenotypic
      variation in plants. In particular, the analysis of 107 quantitative traits
      reported in the first genome-wide association mapping study in Arabidopsis
      thaliana sets the stage for an exciting time in our understanding of plant
      adaptation. We also argue for the need to place phenotype-genotype association
      studies in an ecological context if one is to predict the evolutionary
      trajectories of plant species.

PMID- 21085210
TI  - Chromatic aberrations of radial gradient-index lenses. I. Theory.
AB  - Chromatic effects of radial gradient-index materials have been analyzed, and
      several important conclusions have been derived in terms of material dispersion
      data. The use of Buchdahl dispersion data, both for base glass materials and ion
      exchange pairs, provides some simple relationships for chromatic aberration and
      helps in selecting suitable materials for producing achromatic radial gradient
      index lenses.

PMID- 21085211
TI  - Chromatic aberrations of radial gradient-index lenses. II. Selfoc lenses.
AB  - Simple equations used for analyzing chromatic aberrations of Selfoc lenses were
      derived in terms of Buchdahl chromatic coordinates and Buchdahl dispersion
      constants. The equations that employ gradient-index chromatic constants Psi(1)
      and Psi(2) are used for selecting suitable ion-exchange pairs to design an
      achromatic Selfoc lens.

PMID- 21085212
TI  - Evolution of intracavity fields at a nonsteady state in a dual-recycled
      interferometer.
AB  - I describe how exactly the intracavity fields in a dual-recycling cavity build up
      their power before achieving a steady-state value. The analysis is restricted to
      interferometers with lossless mirrors and a beam splitter. The complete series
      representation of intracavity lights at any stage of evolution in a nonsteady
      state is presented.

PMID- 21085213
TI  - Interferometric 45 degrees  and 60 degrees  strain rosettes: erratum.

PMID- 21085214
TI  - Applications of holographic gratings to two-dimensional spectroscopy.
AB  - Calculations are presented for a set of aberration-corrected holographic concave
      gratings for possible use in space mission instruments. It is concluded that, for
      the visible range 0.26-1.02 MUm when detectors with a 15-MUm pixel size are used,
      a total field of view of ~1 degrees  is possible at an aperture of f/7.0. For the
      infrared regions 0.9-2.5 MUm and 2.4-4.2 MUm, in which detector arrays have
      larger pixel sizes of 30-40 MUm, a spatial field of view of ~2 degrees  at f/7.0
      and ~1.0 degrees  at f/3.5 can be achieved. An exploration of spectrum lengths
      showed that performance starts to fall off sharply for lengths over 15 mm at a
      focal length of 150 mm (i.e., a spectral angular extent of~6 degrees ).

PMID- 21085215
TI  - National Institute of Standards and Technology high-accuracy cryogenic
      radiometer.
AB  - A high-accuracy cryogenic radiometer has been developed at the National Institute
      of Standards and Technology to serve as a primary standard for optical power
      measurements. This instrument is an electrical-substitution radiometer that can
      be operated at cryogenic temperatures to achieve a relative standard uncertainty
      of 0.021% at an optical power level of 0.8 mW. The construction and operation of
      the high-accuracy cryogenic radiometer and the uncertainties in optical power
      measurements are detailed.

PMID- 21085216
TI  - Conditional-sampling spectrograph detection system for fluorescence measurements
      of individual airborne biological particles.
AB  - We report the design and operation of a prototype conditional-sampling
      spectrograph detection system that can record the fluorescence spectra of
      individual, micrometer-sized aerosols as they traverse an intense 488-nm
      intracavity laser beam. The instrument's image-intensified CCD detector is gated
      by elastic scattering or by undispersed fluorescence from particles that enter
      the spectrograph's field of view. It records spectra only from particles with
      preselected scattering-fluorescence levels (a fiber-optic-photomultiplier
      subsystem provides the gating signal). This conditional-sampling procedure
      reduces data-handling rates and increases the signal-to-noise ratio by
      restricting the system's exposures to brief periods when aerosols traverse the
      beam. We demonstrate these advantages by reliably capturing spectra from
      individual fluorescent microspheres dispersed in an airstream. The conditional
      sampling procedure also permits some discrimination among different types of
      particles, so that spectra may be recorded from the few interesting particles
      present in a cloud of background aerosol. We demonstrate such discrimination by
      measuring spectra from selected fluorescent microspheres in a mixture of two
      types of microspheres, and from bacterial spores in a mixture of spores and
      nonfluorescent kaolin particles.

PMID- 21085217
TI  - Small-bore hollow waveguides for delivery of 3-um laser radiation.
AB  - Flexible hollow glass waveguides with bore diameters as small as 250 um have been
      developed for 3-um laser delivery. All the guides exhibit straight losses between
      0.10 and 1.73 dB/m, and the loss increases to between 2.4 and 5.1 dB/m upon
      bending 1 m of the guides into 15-cm-diameter coils. This behavior is shown to
      depend strongly on the launch conditions and mode quality of the input beam. The
      waveguides are capable of efficiently delivering up to 8 W of Er:YAG laser power
      with proper input coupling, and they are suitable for use in both medical and
      industrial applications.

PMID- 21085218
TI  - Linearity of the Faraday-rotation-type ac magnetic-field sensor with a
      ferrimagnetic or ferromagnetic rotator film.
AB  - We analyze the linearity and modulation depth of ac magnetic-field sensors or
      current sensors, using a ferrimagnetic or ferromagnetic film as the Faraday
      rotator and employing the detection of only the zeroth-order optical diffraction
      component from the rotator. It is theoretically shown that for this class of
      sensor the condition of a constant modulation depth and that of a constant ratio
      error give an identical series of curves for the relationship between Faraday
      rotation angle Theta and polarizer/analyzer relative angle Phi. We give some
      numerical examples to demonstrate the usefulness of the result with reference to
      a rare-earth iron garnet film as the rotator.

PMID- 21085219
TI  - Fast, automatically darkening welding filter offering an improved level of
      safety.
AB  - A mode of operation is introduced for the standard 90 degrees  twisted nematic
      (TN) liquid-crystal cell when placed together with an interference filter and
      positioned between crossed polarizers such that a small stimulating voltage of
      between +/-2.0 and +/-13.0 V is required in order to attain the light state.
      Further incrementation of the driving electronics reverts the system back to a
      darker phase. Such cells offer advantages over those of the standard 90 degrees 
      TN device operating in the normally white mode, in that the unit maintains the
      fast response time from the light to the dark state associated with the
      employment of TN cells placed between crossed polarizers. In addition, a low
      transmittance state is achieved when the unit is in the inactivated phase; this
      is an effect usually correlated with the normally black mode of operation. These
      cells are therefore ideal candidates for incorporation into fast, automatically
      darkening, welding filters that are designed to change rapidly from the light to
      the dark protective state, while offering an improved level of safety by not
      holding in a potentially hazardous light state should the controlling electronics
      malfunction. The requirement for this phenomenon to be observed is that the cell
      displays a low optical transmittance over the green wavelengths of the visible
      spectrum when in the inactivated phase and placed between crossed polarizers. The
      presence of an interference filter that possesses a peak transmittance over the
      central part of the visible spectrum is also necessary. It is shown that there
      are only two possible cell types that satisfy this criteria, and the optical
      properties of such cells are analyzed in some detail.

PMID- 21085220
TI  - Uniform-load and actuator influence functions of a thin or thick annular mirror:
      application to active mirror support optimization.
AB  - Explicit analytical expressions are derived for the elastic deformation of a thin
      or thick mirror of uniform thickness and with a central hole. Thin-plate theory
      is used to derive the general influence function, caused by uniform and/or
      discrete loads, for a mirror supported by discrete points. No symmetry
      considerations of the locations of the points constrain the model. An estimate of
      the effect of the shear forces is added to the previous pure bending model to
      take into account the effect of the mirror thickness. Two particular cases of
      general influence are considered: the actuator influence function and the uniform
      load (equivalent to gravity in the case of a thin mirror) influence function for
      a ring support of k discrete points with k-fold symmetry. The influence of the
      size of the support pads is studied. A method for optimizing an active mirror
      cell is presented that couples the minimization of the gravity influence function
      with the optimization of the combined actuator influence functions to fit low
      order aberrations. These low-spatial-frequency aberrations can be of elastic or
      optical origin. In the latter case they are due, for example, to great residual
      polishing errors corresponding to the soft polishing specifications relaxed for
      cost reductions. Results show that the correction range of the active cell can
      thus be noticeably enlarged, compared with an active cell designed as a passive
      cell, i.e., by minimizing only the deflection under gravitational loading. In the
      example treated here of the European Southern Observatory's New Technology
      Telescope I show that the active correction range can be enlarged by ~50% in the
      case of third-order astigmatic correction.

PMID- 21085221
TI  - Optimization of groove depth for cross-talk cancellation in the scheme of land
      groove recording in magneto-optic disk systems.
AB  - In the scheme of land-groove recording in magneto-optic disk data-storage
      systems, it has been shown that an optimum groove depth exists at which the cross
      talk from adjacent tracks diminishes. Crosstalk cancellation, however, is very
      sensitive to various parameters of the system, and, in particular, the presence
      of substrate birefringence can have devastating effects on system performance. We
      analyze the origin of the observed effects by using scalar diffraction theory,
      and we show the reasons behind cross-talk cancellation. We also explain the
      relation between substrate birefringence and cross talk in simple analytical
      terms. Extensive computer simulations have been performed to verify and extend
      the theoretical results of this paper; the results of some of these simulations
      are also presented.

PMID- 21085222
TI  - Optical imaging of inhomogeneous magnetic fields through the deformation of
      paramagnetic liquid films.
AB  - A new quantitative method for optical imaging of inhomogeneous weak magnetic
      fields has been developed, using a thin paramagnetic liquid film on a surface in
      the region of the magnetic field. The deformation of the paramagnetic liquid film
      reveals the magnetic field distribution. The measurements were made
      interferometrically using a version of the Michelson interferometer through which
      an image could be observed. The expected theoretical behavior was developed, and
      the method was investigated experimentally using two different liquids in two
      temperature regions.

PMID- 21085223
TI  - Comparison of two high-precision nondestructive measurement methods for
      evaluating thermal expansion differences in the 8.3-m ultralow-expansion Subaru
      primary mirror blank.
AB  - The building blocks for fabricating the 8.3-m Subaru primary mirror blank are
      ultralow-expansin solid hexagonal units that were subjected to rigorous
      ultrasonic examination to establish thermal expansion characterization as
      reported by Hagy [Appl. Opt. 12, 1440 (1973)]. Following assembly of the mirror
      by fusion and fine annealing, photoelastic analyses at hex-to-hex seals were used
      to calculate thermal expansion differences. These differences are found to be in
      excellent agreement with the ultrasonically established differences.

PMID- 21085224
TI  - Measurement of mode times of flight in multimode fibers by an interferometric
      method using polychromatic light: theoretical approach and experimental results.
AB  - The propagation of several modes in an optical fiber is not easy to study. The
      experiment that we propose permits us to measure the difference in time
      propagation between two successive modes of a multimode fiber. The same laser
      beam is coupled into the fiber to be tested and into the reference single-mode
      fiber. The correlation of output electric fields of the modes propagated by each
      fiber is realized by an interferometric system.

PMID- 21085225
TI  - Phase-based Bragg intragrating distributed strain sensor.
AB  - A strain-distribution sensing technique based on the measurement of the phase
      spectrum of the reflected light from a fiber-optic Bragg grating is described.
      When a grating is subject to a strain gradient, the grating will experience a
      chirp and therefore the resonant wavelength will vary along the grating, causing
      wavelength-dependent penetration depth. Because the group delay for each
      wavelength component is related to its penetration depth and the resonant
      wavelength is determined by strain, a measured phase spectrum can then indicate
      the local strain as a function of location within the grating. This phase-based
      Bragg grating sensing technique offers a powerful new means for studying some
      important effects over a few millimeters or centimeters in smart structures.

PMID- 21085227
TI  - Why do veins appear blue? A new look at an old question.
AB  - We investigate why vessels that contain blood, which has a red or a dark red
      color, may look bluish in human tissue. A CCD camera was used to make images of
      diffusely reflected light at different wavelengths. Measurements of reflectance
      that are due to model blood vessels in scattering media and of human skin
      containing a prominent vein are presented. Monte Carlo simulations were used to
      calculate the spatially resolved diffuse reflectance for both situations. We show
      that the color of blood vessels is determined by the following factors: (i) the
      scattering and absorption characteristics of skin at different wavelengths, (ii)
      the oxygenation state of blood, which affects its absorption properties, (iii)
      the diameter and the depth of the vessels, and (iv) the visual perception
      process.

PMID- 21085226
TI  - Multiplex in-cylinder pressure measurement utilizing an optical fiber with
      specific refractive-index composition.
AB  - An approach to multiplex in-cylinder pressure measurement that utilizes a single
      mode optical fiber with specific refractive-index composition has been proposed.
      The sensing fiber has been designed to show a certain amount of optical power
      loss with a small change in the fiber-local-bend radius. Along with pressure
      transferring diaphragms the sensing fiber was embedded into the head gasket of a
      four-cylinder gasoline engine. The internal-pressure change in each combustion
      chamber was detected on the basis of bending power loss in the fiber. Combustion
      pressure peaks for each cylinder were clearly observed.

PMID- 21085228
TI  - Triangulating laser profilometer as a navigational aid for the blind: optical
      aspects.
AB  - We propose a navigational aid approach for the blind that relies on active
      optical profilometry with real-time electrotactile interfacing on the skin. Here
      we are concerned with the optical parts of this system. We point out the
      particular requirements the profilometer must meet to meet the needs of blind
      people. We show experimentally that an adequate compromise is possible that
      consists of a compact class I IR laser-diode triangulation profilometer with the
      following characteristics: 30-cm to 30-m range, 1-deg angular resolution, 20-ms
      acquisition time per measure of distance, 60 degrees  angular scanning field.

PMID- 21085229
TI  - Optical computing: introduction by the feature editors.
AB  - This feature issue of Applied Optics: Information Processing contains 19 papers
      on Optical Computing. Many of these papers are expanded versions of presentations
      given at the Optical Society of America's Sixth Topical Meeting on Optical
      Computing held in Salt Lake City, Utah, in March 1995. This introduction provides
      a brief historical account of the series of optical computing meetings and a
      brief review of the papers contained in this special issue.

PMID- 21085230
TI  - Large arrays of spatial light modulators hybridized to silicon integrated
      circuits.
AB  - Large, high-frame-rate spatial light modulators are key components required for
      the realization of real-time optical processors. We report a 128 * 128 array of
      GaAs-based optical modulators that we hybridized to a Si integrated circuit by
      using In bump bonds to form a spatial light modulator. These optical modulators
      are composed of a series of quantum wells within an asymmetric Fabry-Perot cavity
      to control the optical properties. The resulting 128 * 128 element array operates
      in an intensity-only reflection mode at greater than 100,000 frames per second.
      This array interfaces to a 486-based personal computer through a standard
      industry standard architecture bus.

PMID- 21085231
TI  - Design and demonstration of a high-speed, multichannel, optical-sampling
      oscilloscope.
AB  - Free-space digital optical systems have demonstrated the capability to provide
      thousands of optical connections between optoelectronic chips. This dense
      concentration of channels creates substantial challenges in monitoring individual
      connections for diagnostic purposes without compromising performance. Prom the
      concept of stroboscopic techniques, we have designed and constructed a
      multichannel optical diagnostic tool that operates analogously to an electronic
      sampling oscilloscope. The tool is economically constructed by the use of
      commercially available video cameras and video-enhanced personal computers. An
      integrated software application operates the tool and displays multiple-channel
      waveforms. We demonstrate the oscilloscope-sampling optical waveforms of a two
      dimensional optoelectronic modulator array operating at data rates from 0.5 to 4
      Gbits/s.

PMID- 21085232
TI  - Decomposition of two-dimensional microlaser patterns.
AB  - For an ordinary individually addressable microlaser array, a separate control
      line is used for each microlaser, which requires a large number of control lines
      for even a small array. An organization that reduces the width of the control
      stream and simplifies packaging is matrix addressing, in which microlasers are
      arranged at the crossings of horizontal and vertical control lines. We consider
      the problem of decomposing arbitrary two-dimensional microlaser patterns into
      matrix-addressable patterns that are applied time sequentially to realize the
      target pattern. We present a mathematical model for the decomposition process and
      present an algorithm for optimal decomposition. We also consider bake factor, in
      which no more than N microlasers in a neighborhood of M (where N < M) are
      enabled, which avoids thermal overload by limiting the density of enabled
      microlasers. We conclude with a case study and show that, for completely
      arbitrary two-dimensional patterns, the average number of time-sequential
      patterns is less than the number of rows in a square array.

PMID- 21085233
TI  - Integration of refractive micro-optical elements with differential-pair optical
      thyristor arrays.
AB  - We demonstrate a refractive micr-optical system by using ion-exchange microlenses
      and microprisms, which are combined to generate a superposition of two shifted
      images. The microlenses, fabricated with field-assisted Ag-Na exchange, achieve
      diffraction-limited imaging with a single-lens system and with a double-lens
      system for a field of 800 um * 800 um. Furthermore, we demonstrate cascading of
      two separate differential-pair optical-thyristor arrays by transcribing the
      information of a source array onto a second destination array.

PMID- 21085234
TI  - Digital Fourier optics.
AB  - Analog Fourier optical processing systems can perform important classes of signal
      processing operations in parallel, but suffer from limited accuracy. Digital
      optical equivalents of such systems could be built that share many features of
      the analog systems while allowing greater accuracy. We show that the digital
      equivalent of any system consisting of an arbitrary number of lenses, niters,
      spatial light modulators, and sections of free space can be constructed. There
      are many possible applications for such systems as well as many alternative
      technologies for constructing them; this paper stresses the potential of free
      space interconnected active-device-plane-based optoelectronic architectures as a
      digital signal processing environment. Implementation of the active-device planes
      through hybridization of optoelectronic components with silicon electronics
      should allow the realization of systems whose performance exceeds that of purely
      electronic systems.

PMID- 21085235
TI  - Analysis of a microchannel interconnect based on the clustering of smart-pixel
      device windows.
AB  - A design analysis of a telecentric microchannel relay system developed for use
      with a smart-pixel-based photonic backplane is presented. The interconnect uses a
      clustered-window geometry in which optoelectronic device windows are grouped
      together about the axis of each microchannel. A Gaussian-beam propagation model
      is used to analyze the trade-off between window size, window density, transistor
      count per smart pixel, and lenslet f-number for three cases of window clustering.
      The results of this analysis show that, with this approach, a window density of
      4000 windows/cm(2) is obtained for a window size of 30 um and a device plane
      separation of 25 mm. In addition, an optical power model is developed to
      determine the nominal power requirements of a 32 * 32 smart-pixel array as a
      function of window size. The power requirements are obtained assuming a
      complementary metal-oxide semiconductor inverter-amplifier and dual-rail multiple
      quantum-well self-electro-optic-effect devices as the receiver stage of the smart
      pixel.

PMID- 21085236
TI  - Optical implementation of visible gray-image morphology with the visual-area
      coding technique.
AB  - We present a novel scheme of visible gray-image morphology with the visual-area
      coding technique (VACT). The VACT is a technique of digitized analog-optical
      computing in which data are converted into visible coded patterns and processed
      with the visible form. Because the achievable operations in the VACT are
      identical to those of mathematical morphology, mathematical morphology is adapted
      to gray-image morphology with the VACT. Computer simulation and optical
      experiments of the several operations in mathematical morphology verify the
      correctness of the proposed technique. The processing capacity of the proposed
      method is estimated in terms of the space-bandwidth product.

PMID- 21085237
TI  - Performance trade-offs for conventional lenses for free-space digital optics.
AB  - We describe the limitations on the use of conventional lenses in optical
      computing that arise from manufacturing tolerances. The consequences on maximum
      array size, minimum device size, and propagation delay of systems are discussed.
      Two experimental optical computing systems are then compared with these results.
      We show that there are maximum and minimum bounds on the focal length and the f
      number of lenses imposed when manufacturing tolerances are considered. We also
      show that there are maximum bounds on image sizes and space-bandwidth products
      and trade-offs between spot size and system latency.

PMID- 21085238
TI  - Realizing optical logic with a smart-pixel spatial light modulator.
AB  - A method of implementing optical logic has been realized experimentally with a
      novel liquid crystal on silicon spatial light modulator with an integrated lens
      arrays. The device allows for three optical inputs and one optical output per
      pixel. The different logic functions realized, OR, and, nor, nand, and xor, are
      discussed.

PMID- 21085239
TI  - Reconfigurable intelligent optical backplane for parallel computing and
      communications.
AB  - A reconfigurable intelligent optical backplane architecture for parallel
      computing and communications is described. The backplane consists of a large
      number of reconfigurable optical channels organized in a ring with relatively
      simple point-to-point optical interconnections between neighboring smart-pixel
      arrays. The intelligent backplane can implement (l) dynamically reconfigurable
      connections between any printed circuit boards, (2) dynamic embeddings of
      classical interconnection networks such as buses, rings, multidimensional meshes,
      hypercubes, shuffles, and crossbars, (3) multipoint switching, (4) sorting, (5)
      parallel-prefix operations, (6) pattern-matching operations, (7) snoopy caches
      and intelligent memory systems, and (8) media-access control functions. The smart
      pixel arrays can be enhanced to include more complex functions, such as queuing
      and routing, as the technologies mature. Descriptions of the architecture and the
      smart-pixel arrays and discussions of the system cost, availability, and
      performance are included.

PMID- 21085240
TI  - Experimental free-space optical network for massively parallel computers.
AB  - A free-space optical interconnection scheme is described for massively parallel
      processors based on the interconnection-cached network architecture. The optical
      network operates in a circuit-switching mode. Combined with a packet-switching
      operation among the circuit-switched optical channels, a high-bandwidth, low
      latency network for massively parallel processing results. The design and
      assembly of a 64-channel experimental prototype is discussed, and operational
      results are presented.

PMID- 21085241
TI  - VCSEL-array-based angle-multiplexed optoelectronic crossbar interconnects.
AB  - A large crossbar switch, which is a desirable building block for any low-latency
      interconnect network, is difficult to implement because of many practical
      problems associated with digital electronics. We propose a new method for
      implementing a large optoelectronic crossbar interconnect to take advantage of a
      unique principle of optics. Based on an emerging vertical-cavity surface-emitting
      laser (VCSEL) technology, a passive angle-multiplexed beam-steering architecture
      is proposed as a key component of the optoelectronic crossbar. Various optical
      system parameters are evaluated. Because there is no optical fan-out power loss,
      the interconnect capacity of the proposed system is determined by the diffraction
      limited receiver power cutoff, and therefore interconnection of more than 1000
      nodes with a per node bandwidth of 1 GHz is possible with today's technology. A
      64-element VCSEL-array-based proof-of-principle optical system for studying the
      interconnect scalability has been built. Details of the features of the proposed
      system, its advantages and limitations, demonstration experimental results, and
      their analyses are presented.

PMID- 21085242
TI  - Feasibility study of a scalable optical interconnection network for massively
      parallel processing systems.
AB  - The theoretical modeling of a novel topology for scalable optical interconnection
      networks, called optical multimesh hypercube (OMMH), is developed to predict
      size, bit rate, bit-error rate, power budget, noise, efficiency, interconnect
      distance, pixel density, and misalignment sensitivity. The numerical predictions
      are validated with experimental data from commercially available products to
      assess the effects of various thermal, system, and geometric parameters on the
      behavior of the sample model. OMMH is a scalable network architecture that
      combines positive features of the hypercube (small diameter, regular, symmetric,
      and fault tolerant) and the mesh (constant node degree and size scalability). The
      OMMH is implemented by a free-space imaging system incorporated with a space
      invariant hologram for the hypercube links and fiber optics to provide the mesh
      connectivity. The results of this work show that the free-space links can operate
      at 368 Mbits/s and the fiber-based links at 228 Mbits/s for a bit-error rate of
      10(-17) per channel. The predicted system size for 32 nodes in the OMMH is 4.16
      mm * 4.16 mm * 3.38 cm. Using 16-bit, bit-parallel transmission per node, the
      system can operate at a bit rate of up to 5.88 Gbits/s for a size of 1.04 cm *
      1.04 cm * 3.38 cm.

PMID- 21085243
TI  - Electrophotonic computer networks with strictly nonblocking and self-routing
      functions.
AB  - Three-stage optical interconnection networks for use in massively parallel
      processors are proposed. Wavelength-division- and space-division-multiplexing
      switches used in these networks are described, and free-space optics to assist in
      the construction of networks that are small and provide high throughput are
      discussed.

PMID- 21085244
TI  - Tolerancing of board-level-free-space optical interconnects.
AB  - For optical interconnects to become a mature technology they must be amenable to
      electronic packaging technology. Two main obstacles to including free-space
      optical interconnects are alignment and heat-dissipation issues. Here we study
      the issues of alignment tolerancing that are due to assembly and manufacturing
      variations (passive-element tolerancing) over long board-level distances (>10 cm)
      for free-space optical interconnects. We also combine these variations with
      active optoelectronic device variations (active-element tolerancing). We
      demonstrate a computer-aided analysis procedure that permits one to determine
      both active- and passive-element tolerances needed to achieve some system-level
      specification, such as yield or cost. The procedure that we employ relies on
      developing a detailed design of the system to be studied in a standard optical
      design program, such as code v. Using information from this model, we can
      determine the integrated power falling on the detector, which we term optical
      throughput, by performing Gaussian propagation or general Fresnel propagation (if
      significant vignetting occurs). This optical throughput can be used to determine
      system-level performance criteria, such as bit-error rate. With this computer
      aided analysis technique, a sensitivity analysis of all the variations under
      study is made on a system with realistic board-level interconnect distances to
      find each perturbation's relative effects (with other perturbations set to 0) on
      the power falling on the detector. This information is used to set initial
      tolerances for subsequent tolerancing analysis and design runs. A tolerancing
      analysis by Monte Carlo techniques is applied to determine if the yield or cost
      (yield is denned as the percentage of systems that have acceptable system
      performance) is acceptable. With a technique called parametric sampling, a
      subsequent tolerancing design run can be applied to optimize this yield or cost
      with little increase in computation. We study a design example and show that most
      of the tolerances can be achieved with current technology.

PMID- 21085245
TI  - Convergence of backward-error-propagation learning in photorefractive crystals.
AB  - We analytically determine that the backward-error-propagation learning algorithm
      has a well-defined region of convergence in neural learning-parameter space for
      two classes of photorefractive-based optical neural-network architectures. The
      first class uses electric-field amplitude encoding of signals and weights in a
      fully coherent system, whereas the second class uses intensity encoding of
      signals and weights in an incoherent/coherent system. Under typical assumptions
      on the grating formation in photorefractive materials used in adaptive optical
      interconnections, we compute weight updates for both classes of architectures.
      Using these weight updates, we derive a set of conditions that are sufficient for
      such a network to operate within the region of convergence. The results are
      verified empirically by simulations of the xor sample problem. The computed
      weight updates for both classes of architectures contain two neural learning
      parameters: a learning-rate coefficient and a weight-decay coefficient. We show
      that these learning parameters are directly related to two important design
      parameters: system gain and exposure energy. The system gain determines the ratio
      of the learning-rate parameter to decay-rate parameter, and the exposure energy
      determines the size of the decay-rate parameter. We conclude that convergence is
      guaranteed (assuming no spurious local minima in the error function) by using a
      sufficiently high gain and a sufficiently low exposure energy per weight update.

PMID- 21085246
TI  - Photorefractive processing for large adaptive phased arrays.
AB  - An adaptive null-steering phased-array optical processor that utilizes a
      photorefractive crystal to time integrate the adaptive weights and null out
      correlated jammers is described. This is a beam-steering processor in which the
      temporal waveform of the desired signal is known but the look direction is not.
      The processor computes the angle(s) of arrival of the desired signal and steers
      the array to look in that direction while rotating the nulls of the antenna
      pattern toward any narrow-band jammers that may be present. We have
      experimentally demonstrated a simplified version of this adaptive phased-array
      radar processor that nulls out the narrow-band jammers by using feedback
      correlation detection. In this processor it is assumed that we know a priori only
      that the signal is broadband and the jammers are narrow band. These are examples
      of a class of optical processors that use the angular selectivity of volume
      holograms to form the nulls and look directions in an adaptive phased-array-radar
      pattern and thereby to harness the computational abilities of three-dimensional
      parallelism in the volume of photorefractive crystals. The development of this
      processing in volume holographic system has led to a new algorithm for phased
      array-radar processing that uses fewer tapped-delay lines than does the classic
      time-domain beam former. The optical implementation of the new algorithm has the
      further advantage of utilization of a single photorefractive crystal to implement
      as many as a million adaptive weights, allowing the radar system to scale to
      large size with no increase in processing hardware.

PMID- 21085247
TI  - High-accuracy optical computing based on interval arithmetic and the fixed-point
      theorem.
AB  - A method for high-accuracy analog optical computing based on interval arithmetic
      and the fixed-point theorem is considered. Two-variable simultaneous equations
      are studied to investigate the proposed method. An optical implementation is
      considered by the use of spatial coding of intervals, affine transformation, and
      image magnification. Computational simulation verifies the principle of the
      method.

PMID- 21085248
TI  - Optical lateral inhibition networks that use self-linearized self-electro-optic
      effect devices: theory and experiment.
AB  - The self-linearized self-electro-optic-effect-device (SL-SEED) phenomenon
      observed with a quantum-well modulator and photodiode serial combination is one
      of the few practical routes to optical subtraction. A family of optical lateral
      inhibition architectures based on the SL-SEED that incorporate optical feedback
      is introduced and their operation confirmed in simulation. A successful
      experimental demonstration based on these ideas, performing edge-contrast
      enhancement by lateral inhibition, is described. System interconnections are both
      optical and electrical, with nonlocal interconnections being made optically by
      the use of diffractive elements.

PMID- 21085249
TI  - Plane-wave theory of a Michelson laser coupler with a dielectric slab beam
      splitter.
AB  - The plane-wave theory for the transmittance and absorbtance of a perfectly
      aligned Michelson coupler with a dielectric slab beam splitter is presented. It
      is shown that the transmittance and absorbtance vary sinusoidally and in
      quadrature. As a result of this quadrature relationship, the maximum
      transmittance occurs at a setting of the translatable coupler mirror at which the
      absorbtance is not at an extremum, and so the curve of output power as a function
      of coupler setting is asymmetrical with respect to the setting yielding maximum
      transmittance. Experimental measurements of the output power of a far-infrared
      HCN laser as a function of the coupler setting confirm this asymmetry, which
      seems to have been overlooked or ignored in previous studies.

PMID- 21085250
TI  - Optical constants of various chromites as determined by Kramers-Kronig analysis.
AB  - The infrared optical constants of a few different powders of chromites,
      XCr(2)O(4) (where X is Fe, Ni, Mg, Zn, or Cu), have been determined by Kramers
      Kronig analysis of their infrared transmission and reflection spectra. The
      knowledge of these constants allows one to predict the different thin-layer
      infrared reflection spectra and to compare them, when it is possible, with the
      reflection spectra calculated with n and k obtained by the use of the classical
      oscillator method.

PMID- 21085251
TI  - High-power dye laser using steady-state amplification with chirped pulses.
AB  - Steady-state chirped-pulse amplification was applied to a five-stage dye
      amplifier system to extract available energy over the full gain duration and at
      the same time suppress the amplified spontaneous emission (ASE). An output energy
      of 41 mJ was generated with 1.4-ns chirped pulses having an ASE of 3% and a
      pumping efficiency of 8.8% for the final amplifier. After five-stage
      amplification these pulses were compressed to 320 fs FWHM.

PMID- 21085252
TI  - Thermally induced strain and birefringence calculations for a Nd:YAG rod
      encapsulated in a solid pump light collector.
AB  - Calculations and experimental measurements of the thermally induced strain and
      birefringence are presented for a diode-pumped Nd:YAG rod that is encapsulated in
      a prismatic pump light collector. A numerical model is developed to determine the
      spatiotemporal stress-induced strain distribution across the prism, index
      matching fixant, and laser rod, and the birefringence that arises from the stress
      induced strain within the laser rod. Calculations of the birefringence are
      compared with polarscopic measurements and display good agreement. Support for
      the rod on all sides is provided by the prism and fixant, and the distribution
      and degree of the stress-induced strain (and birefringence) within the laser rod
      are therefore influenced by the geometry and composition of the prism and fixant.
      These strains are thermomechanical in origin and are primarily a function of the
      elastic modulus of the fixant and the temperature of the system. Such stress
      induced strains are additional to those strains that are produced from
      temperature gradients across the laser rod and result from the laser rod being
      constrained from expanding. Collectors utilizing index-matching fluid as the
      encapsulant display the smallest measure of birefringence relating to the
      temperature gradients in the rod. However, for collectors utilizing solid fixants
      (with significant elastic modulus), an increase in the birefringence results. In
      this case collector designs that have the laser rod located in a symmetrically
      shaped prism are effective in reducing the nonuniform pressures on the sides of
      the rod and therefore the birefringence.

PMID- 21085253
TI  - Laser-diode end-pumped Tm(3+):YAG eye-safe laser.
AB  - The lasing characteristics of a laser-diode end-pumped Tm:YAG laser were
      investigated. We obtained a laser output power of 124 mW, a slope efficiency of
      36%, and a threshold power of 77 mW with a 3% Tm-doped YAG crystal at room
      temperature. This lasing performance was improved when the crystal was cooled.
      The dependencies of both slope efficiency and threshold power on temperature were
      measured.

PMID- 21085254
TI  - Demonstration and characterization of a multibillion-shot, 2.5-mJ, 4-ns, Q
      switched Nd:YAG laser.
AB  - We have demonstrated and characterized a Q-switched Nd:YAG laser under continuous
      operation for over 7 billion shots. Through periodic monitoring of the laser's
      vital signs, the system dynamics were decoupled to identify the sources of
      degradation. The initial and the final pump-laser diode wavelengths and powers
      were measured and compared. No evidence of an accumulative effect leading to
      optical damage at a fluence lower than the single-shot threshold was observed.

PMID- 21085255
TI  - Efficient Nd:YAG laser end pumped by a high-power multistripe laser-diode bar
      with multiprism array coupling.
AB  - A 10-W laser-diode bar, a multistripe monolithic laser-diode array, has been used
      to end pump Nd:YAG. Twelve beams emitted from 12 stripes, spaced 800 um apart, of
      a 1-cm linear diode array were collimated with a multiprism array consisting of
      14 prismlets with 800-um width to pump the Nd:YAG facet. The maximum Nd:YAG cw
      output power at 1064 nm of 3 W was obtained at 10-W laser-diode-bar power with a
      slope efficiency of 35%, and a TEM(00) spatial mode with values of beam-quality
      factor M(2) of 1.29 and 1.76 in the planes perpendicular and parallel to the
      junction, respectively. A pulse width of 25.2 ns (1-kHz repetition) was obtained
      in acousto-optic Q-switched operation.

PMID- 21085256
TI  - Single-mode diode laser with a large frequency-scanning range based on weak
      grating feedback.
AB  - A single-mode GaAlAs diode laser with over 90% output-coupling power and a large
      frequency-scanning range is reported. Based on grating feedback in the Littrow
      configuration, it is demonstrated that, with weak feedback (1.5 * 10(-3) in this
      experiment), over a 7.5-GHz continuous tuning range can be achieved around tuning
      gaps of free-running operation. A frequency self-locking effect is also
      demonstrated in this system.

PMID- 21085257
TI  - Nonparaxial analysis of the far-field radiation patterns of double
      heterostructure lasers.
AB  - Previous analytical approximations for the far-field radiation patterns of a
      double-heterostructure laser have been restricted by TE-mode propagation in slab
      waveguides. A model that is applicable to both TE- and TM-mode propagation either
      in a slab waveguide or in a multiple-quantum-well structure is developed. Results
      of computations agree with the measured irradiance profiles of visible diode
      lasers of wavelengths from 635 to 670 nm. A process for deriving far-field
      expressions in terms of the diode-laser parameters listed in data books is
      suggested. Astigmatic aberration present in the wave front is determined, and the
      final result is expressed in a form convenient for diffraction analysis of
      truncated focused (or collimated) diode-laser beams.

PMID- 21085258
TI  - Optical parametric amplifiers: a discrete dynamical model of singly resonant
      operation leading to a novel approach to the design of systems for high
      efficiency amplification.
AB  - A simple plane-wave model of pulsed, singly resonant, optical-parametric
      oscillator and optical-parametric-oscillator-amplifier operation leads to a
      description of such systems in terms of a discrete dynamical system. The
      theoretical limits on conversion efficiencies derivable from this model were
      explored. Analysis of the model for an optical parametric oscillator-amplifier
      (OPOA) indicates that the effect that backconversion has in limiting efficiency
      can be avoided if one precisely shapes the time profile of the pump pulse and
      combines it with an OPOA that is Q switched. For a case of type I phase matching
      with beta-barium borate with a specific pump profile and a 65-mJ input pulse,
      under the assumption of small absorption, the following are demonstrated: (l) the
      theoretical possibility of amplification to a few joules at quantum efficiencies
      higher than 90% and (2) the possibility of amplification to approximately 1 J at
      an energy efficiency near 45% in a configuration satisfying realistic stress
      constraints. Pulse widths are in the nanosecond range, and spot sizes are in the
      millimeter range. Issues of implementation are discussed.

PMID- 21085259
TI  - Absolute frequency stabilization of an injection-seeded optical parametric
      oscillator.
AB  - A method is described that provides absolute frequency stabilization and
      calibration of the signal and idler waves generated by an injection-seeded
      optical parametric oscillator (OPO). The method makes use of a He-Ne stabilized
      transfer cavity (TC) to control the frequencies of the cw sources used to seed
      both the pump laser and OPO cavity. The TC serves as a stable calibration source
      for the signal and idler waves by providing marker fringes as the seed laser is
      scanned. Additionally, an acoustic-optic modulator (AOM) is used to shift the OPO
      seed laser's frequency before locking it onto the TC. The sidebands of the AOM
      are tunable over more than one free spectral range of the TC, thereby permitting
      stabilization of the signal and idler waves at any frequency. A +/-25-MHz
      residual error in the absolute frequency stabilities of the pump, signal, and
      idler waves is experimentally demonstrated, which is roughly 30% of the 160-MHz
      near-transform-limited linewidths of the signal and idler pulses.

PMID- 21085260
TI  - Generation of tunable, narrow-band mid-infrared radiation through a 532-nm-pumped
      KTP optical parametric amplifier.
AB  - We report generation of broadly tunable (2.5-4 um), narrow-band (0.04-0.35 cm-1)
      pulsed infrared radiation through a nanosecond optical parametric amplifier based
      on potassium titanyl phosphate (KTP) pumped by the second harmonic of a 10-Hz
      Nd:YAG laser. Input radiation at signal wavelengths of 615-662 nm was derived
      from a pulsed tunable dye laser system. Advantages of this device are simplicity,
      the broad range of infrared wavelengths to which a single dye in the dye laser
      provides access, and conversion efficiencies >10% at modest levels (<150 uJ) of
      input radiation.

PMID- 21085261
TI  - Characteristics analysis of wavelength-division-multiplexing fiber couplers
      fabricated with a microheater.
AB  - Optical properties and taper profiles of 1.3l/l.55-um wavelength-division
      multiplexing (WDM) fiber couplers have been experimentally analyzed. A newly
      developed microheater was used for the fabrication in air. The elongation lengths
      were controlled so that the fourth coupling peak would reach the 1.55-um
      wavelength. The wavelength difference Deltalambda between the peak coupling
      wavelength of 1.55 um and that around 1.31 um decreased linearly at each fusion
      temperature with the fusion time. At each fusion temperature, the Deltalambda
      value decreased linearly with the elongation length and decreased exponentially
      with the neck width. The Deltalambda value and the taper shape at the minimum
      limit of the degree of fusion were estimated. The fabrication condition and the
      taper shape for 1.31-um and 1.55-um WDM coupling were also analyzed.

PMID- 21085262
TI  - Nonlinear-index-of-refraction measurement in a resonant region by the use of a
      fiber Mach-Zehnder interferometer.
AB  - The nonlinear index of refraction in a resonant region has been determined by the
      use of a fiber-based Mach--Zehnder interferometer to measure the temporal fringe
      shift between two signals. The measurement technique is direct and does not
      require additional amplitude information for the extraction of the nonlinear
      index of refraction. This technique has been used to measure the temporal
      response of an InGaAsP semiconductor optical amplifier at 1.313 um.

PMID- 21085263
TI  - Effect of water vapor in a y-cut lithium niobate waveguide.
AB  - In z-cut lithium niobate (LiNbO3) samples, surface damage has been observed after
      diffusion in a wet atmosphere, but recent reports show that with controlled flow
      of water vapor waveguides with good surface morphology and low loss can be
      obtained. Y-cut waveguides do not show any surface damage. Fabrication of y-cut
      waveguides diffused with controlled variation of water vapor in the ambient has
      not been reported to the best of our knowledge. We show that a minimum loss in y
      cut waveguides is obtained at a particular water vapor content in the ambient,
      which is lower than the loss obtained for waveguides diffused in dry ambient. We
      have found a decrease in the waveguide loss to 0.3 dB/cm from 0.6 dB/ cm for 1 mL
      of water vapor passed per hour as compared with a dry atmosphere.

PMID- 21085264
TI  - Theoretical waveguide optimization in a Ti:LiNb0(3) Mach-Zehnder modulator by Mg
      diffusion.
AB  - Magnesium diffusion can be used to optimize the characteristics and performance
      of a Ti:LiNbO(3) Mach-Zehnder modulator. Suitable use of titanium/magnesium
      double diffusion reduces fiber-waveguide coupling loss, minimizes the modulator
      size by increasing the bend radius of curvature without increasing bend losses,
      and decreases separation of the modulator arms. The proposed method also makes it
      possible to reduce the modulating voltage by improvement of guided-wave lateral
      confinement. Secondary ion mass spectrometry and 771-line techniques are used to
      characterize Ti/Mg:LiNbO(3) waveguides. A numerical optimization procedure based
      on the full vectorial beam-propagation method is presented.

PMID- 21085265
TI  - Fabrication of channel waveguides from sol-gel-processed polyvinylpyrrolidone/
      SiO(2) composite materials.
AB  - Sol-gel-processed composite materials of polyvinylpyrrolidone (PVP) and SiO(2)
      were studied for optical waveguide applications. PVP is a polymer that can be
      crosslinked, so it is expected to have high thermal stability after crosslinking.
      However, thermal crosslinking and thermal decomposition of pure PVP take place
      around the same temperature, 200  degrees C, therefore pure PVP had a high
      optical propagation loss as a result of the absorption of the decomposed
      molecules after crosslinking. The incorporation of sol-gel-processed SiO(2)
      prevented the thermal decomposition of PVP and provided remarkably low optical
      propagation losses. The PVP/SiO(2)composite material also produced thick (>2-um)
      crack-free films when the PVP concentration was 50% or higher. An optical
      propagation loss of 0.2 dB/cm was achieved at 633 nm in the 50% PVP/SiO(2)
      composite planar waveguide. Several aspects of the thermal stability of the
      waveguides were evaluated. The slab waveguide was then used for fabrication of
      channel waveguides with a selective laser-densification technique. This technique
      used metal lines fabricated with photolithography on the slab waveguide as a
      light absorbent, and these metal lines were heated by an Ar laser. The resultant
      channel waveguide had an optical propagation loss of 0.9 dB/ cm at 633 nm. This
      technique provides lower absorption loss and scattering loss compared with the
      direct laser-densification technique, which uses UV lasers, and produces narrow
      waveguides that are difficult to fabricate with a CO(2) laser.

PMID- 21085266
TI  - Weighted distributed feedback structure for all-optical bistable devices.
AB  - We proposed to use a distributed feedback structure with a weighted coupling
      coefficient (W-DPB) in an all-optical bistable device in order to improve on
      state transmittance and to reduce threshold intensity. Through numerical
      calculations, characteristics of the W-DPB structure were discussed compared with
      those of a conventional DPB structure. The W-DPB optical bistable device exhibits
      high on-state transmittance and low-threshold input intensity. Fabrication of the
      W-DPB structure with a periodicity of 169.8 nm is demonstrated on a CdS(x)Se(1-x)
      doped glass substrate by means of holographic exposure with a double-coated
      photoresist and reactive ion etching in CHP(3).

PMID- 21085267
TI  - Iterative method to determine an averaged backscatter-to-extinction ratio in
      cirrus clouds.
AB  - An iterative method to determine an average backscatter-to-extinction ratio and
      extinction coefficient simultaneously in cirrus clouds is proposed. The method is
      based on Klett's inversion, which is constrained by the total optical depth. A
      signal-to-noise ratio greater than 3 at the cloud top is required for an error in
      the backscatter-to-extinction ratio lower than 20% to result. The method has been
      tested with simulated lidar signals. An application to an experimental lidar
      signal is discussed.

PMID- 21085268
TI  - Laboratory technique for the measurement of thermal-emission spectra of
      greenhouse gases: CFC-12.
AB  - A new technique has been developed to make possible the laboratory study of the
      infrared-emission spectra of gases of atmospheric interest. The thermal-emission
      spectra are in local thermodynamic equilibrium, just as they are in the
      atmosphere, and are not chemiluminescent. Demonstration results obtained by the
      use of this new technique are presented for dichlorodifluoromethane (CFC-12) at a
      pressure of 0.5 Torr in a cell with a path length of 5 cm. The measured cell
      spectra have been compared with simulations with the FASCD3P radiation code. The
      measurements of the emission spectra of radiatively active gases may be important
      for the atmospheric greenhouse effect and global warming.

PMID- 21085269
TI  - Mid-infrared measurements of the atmospheric emission over the South Pole using a
      radiometrically calibrated Fourier transform spectrometer.
AB  - We conducted year-round measurements of the downwelling atmospheric infrared
      emission over the South Pole in 1992. The instrument covered the 550-1600-wave
      number region with 1-wave-number resolution. We calculated the water vapor
      content for clear-sky cases and found a good correlation with the surface
      temperature, with values ranging from 0.2 to 0.8 mm. Ozone-sonde profiles were
      compared with total column abundances of O(3) retrieved from the spectra. The
      experiment is explained in detail, including the instrumentation, calibration,
      and retrieval methods used. The calibrated spectra contain information about
      several trace gases, water, clouds, temperature profiles, and aerosols.

PMID- 21085270
TI  - Optimal bandwidth for topographical differential absorption lidar detection.
AB  - A detected laser signal backscattered from a tilted target is modeled with a
      laser-pulse shape as a response of a high-pass filter to an exponential input
      that describes the gain buildup within the laser cavity before a laser pulse is
      emitted and a single-pole low-pass RC filter for the electronic amplifier. The
      model is used to maximize the signal-to-noise ratio of the detected peak signal
      with a proper choice of the integration time constant tau as a function of the
      laser-pulse shape and the tilt angle of the backscattering target.

PMID- 21085271
TI  - Discussion of two quadrature methods of evaluating beam-shape coefficients in
      generalized Lorenz-Mie theory.
AB  - A comparison between two quadrature methods of evaluating beam-shape coefficients
      in generalized Lorenz-Mie theory, in the case of incident Gaussian beams, is
      carried out. It is shown that, when the electromagnetic description of the
      Gaussian beams does not perfectly satisfy Maxwell's equations, both quadrature
      methods are basically flawed. These flaws do not prevent an accurate evaluation
      of beam-shape coefficients when their nature is correctly identified, because
      they produce artifacts that can easily be identified and removed.

PMID- 21085272
TI  - Partial-wave expansions and properties of axisymmetric light beams.
AB  - Axisymmetric light beams are defined as light beams for which the component of
      the Poynting vector in the direction of propagation does not depend on the
      azimuthal angle in suitably chosen coordinate systems to reveal the symmetric
      property of the beam. It is shown that such beams are encoded in a set of beam
      shape coefficients gn that are, however, defined in a more general way than usual
      in the case of Gaussian beams. Partial-wave expansions and properties of such
      beams are studied.

PMID- 21085273
TI  - Measurements of the four-point coherence function by the use of the coherence
      enhancement phenomenon.
AB  - We present laboratory results for measurements of the four-point coherence
      function of a spherical wave in the region of coherence enhancement after
      backscattering through turbulence. Experimental results are compared with the
      theoretical predictions. We conclude that the shape of the four-point coherence
      function in our experiment depends on the value of the inner scale of turbulence.

PMID- 21085274
TI  - Simulations of time series of atmospherically distorted wave fronts.
AB  - A comparatively simple way to generate time series of atmospherically distorted
      wave fronts is described and tested. Temporal power spectra of Zernike
      aberrations, extracted from the time series, agree very well with theoretical
      predictions. A method for generation of longer time series is also shown to give
      results in accordance with theory, except for the lowest temporal frequencies
      modeled. A way to superimpose several time series of wave fronts to generate a
      multilayer model of the atmosphere is briefly discussed.

PMID- 21085275
TI  - Refractive index of air: new equations for the visible and near infrared.
AB  - The precision of modern length interferometry and geodetic surveying far exceeds
      the accuracy, which is ultimately limited by the inadequacy of currently used
      equations for the refractive index of the atmosphere. I have critically reviewed
      recent research at the National Physical Laboratory, the International Bureau of
      Weights and Measures, and elsewhere that has led to revised formulas and data for
      the dispersion and density of the major components of the atmosphere. I have
      combined selected formulas from these sources to yield a set of equations that
      match recently reported measurements to within the experimental error, and that
      are expected to be reliable over very wide ranges of atmospheric parameters and
      wavelength.

PMID- 21085276
TI  - Modeling a variable-focus liquid-filled optical lens.
AB  - Research has been conducted on a variable-focus liquid-filled optical lens built
      from a polymer elastic-film window and a rigid plastic window with a transparent
      refractive liquid between these windows. The pressure inside the lens deforms the
      elastic film, which takes the form of a paraboloid. The absolute value of the
      tension in the film was calculated, allowing theoretical evaluation of the focal
      length of the lens and its aberrations. The developed mathematical model of the
      liquid-filled flexible lens agrees well with experimental results.

PMID- 21085277
TI  - Axial tolerance in the position of aberration compensators placed in a converging
      beam.
AB  - To perform a null test of aspherical surfaces we used a computer-generated
      hologram or a lens or a mirror compensator to compensate the aspherical
      aberration. When compensating in a convergent light beam the axial position of
      this hologram or compensator is critical. A holographic compensator to be used in
      the convergent beam of light was designed and constructed. We have established
      some relations to determine the tolerance in the axial positioning of these
      compensators.

PMID- 21085278
TI  - Variable separation in curvature sensing: fast method for solving the irradiance
      transport equation in the context of optical telescopes.
AB  - A method to evaluate wave-front aberrations in optical telescopes that is based
      on the method of curvature sensing but that solves the irradiance transport
      equation by variable separation is presented. This technique is simpler for
      processing than are previously released techniques and can perform more
      efficiently, as is required by active and adaptive optics. Testing for
      consistency of the method by evaluation of several sets of out-of-focus images
      obtained with the 2-m telescope at the Universidad Nacional Autonoma de Mexico
      was carried out, and a stability of 10% for the derived values of Zernike
      coefficients was found.

PMID- 21085279
TI  - Transient response in doped germanium photoconductors under very low background
      operation.
AB  - Doped germanium photoconductors are the most sensitive detectors for astronomy in
      the wavelength range 40-240 um. Under the extremely low background conditions
      encountered in cooled satellite instruments, these devices exhibit a number of
      transient effects, such as slow relaxation after a step change in illumination or
      bias, and spontaneous spiking at high signal levels. Such behavior can degrade
      the excellent instantaneous sensitivity of these detectors and create calibration
      uncertainties. These effects have been observed in the Ge:Be photoconductors and
      the stressed and unstressed Ge:Ga photoconductors in the Long Wavelength
      Spectrometer, one of the instruments on the Infrared Space Observatory. A
      systematic investigation of the transient response of the Long Wavelength
      Spectrometer detectors to a step change in illumination as a function of
      operating temperature, bias electric field, and illumination step size has been
      carried out to determine operating conditions that minimize the effects of this
      behavior. The transient effects appear to be due primarily to carrier sweep out,
      but they are not fully explained by existing models for transient response.

PMID- 21085280
TI  - Fresnel diffraction from curved fiber snippets with application to fiber diameter
      measurement.
AB  - Fiber curvature is examined for its effect on apparent measured fiber diameter in
      a double-diffraction-based instrument that is in widespread use in the wool
      industry. The development uses a two-dimensional Fresnel diffraction model. The
      magnitude of the effect is studied for 2-mm-long snippets of various diameters
      from 8 to 50 um and with radii of curvature of 1 m (straight), 600 um, 280 um,
      200 um, and 160 um. The two-dimensional Fresnel model gives rise to deeply nested
      vector integrations that make computations with a straightforward approach
      exceedingly time consuming and impractical. A number of simplifying techniques
      are used to facilitate and speed up the numerical computations, thereby
      permitting investigations to be carried out on a personal computer.

PMID- 21085281
TI  - Fringe formation in multiaperture speckle shear interferometry.
AB  - Multiaperture speckle shear interferometry exhibits sensitivity to in-plane
      displacement components. The response of the interferometer to in-plane
      displacement, however, depends on the location of the shear element on an
      aperture in front of the imaging lens. Two configurations with three apertures,
      with the shear element positioned at two different locations, are examined
      theoretically and experimentally.

PMID- 21085282
TI  - External phase-modulation interferometry.
AB  - We analyze and test a laboratory benchtop version of a compound interferometric
      phase sensor, a Michelson interferometer whose output is combined coherently with
      a phase-modulated local oscillator beam tapped off the Michelson input beam. This
      configuration models a whole class of external-modulation interferometers
      designed to shift signals, obscured by low-frequency intensity noise of the light
      source, into a shot-noise-limited region of the photocurrent spectrum. We find
      analytically that the shot-noise-limited sensitivity achievable with this system
      is comparable with that obtained by using internal phase modulation, with both
      schemes suffering (for different reasons) approximately a 22% sensitivity penalty
      compared with ideal shot-noise-limited direct detection. Experimentally we
      achieve true shot-noise-limited sensitivity, and we investigate trade-offs
      necessitated by commonly encountered nonideal features in any external-modulation
      system. Our analytic model, which specifically accounts for Michelson fringe
      contrast, electronic receiver noise, phase-modulation depth, and the local
      oscillator tap-off fraction, is sufficiently accurate to predict the absolute
      sensitivity of our benchtop instrument to within 0.5 dB.

PMID- 21085283
TI  - Liquid-crystal point-diffraction interferometer for wave-front measurements.
AB  - A new instrument, the liquid-crystal point-diffraction interferometer (LCPDI), is
      developed for the measurement of phase objects. This instrument maintains the
      compact, robust design of Linnik's point-diffraction interferometer and adds to
      it a phase-stepping capability for quantitative interferogram analysis. The
      result is a compact, simple to align, environmentally insensitive interferometer
      capable of accurately measuring optical wave fronts with very high data density
      and with automated data reduction. We describe the theory and design of the
      LCPDI. A focus shift was measured with the LCPDI, and the results are compared
      with theoretical results.

PMID- 21085284
TI  - Path-independent phase unwrapping of subsampled phase maps.
AB  - A technique for unwrapping subsampled phase maps is presented. The subsampled
      phase map is obtained by standard phase-shifting methods that use subsampled
      interferograms. The technique then estimates the wrapped local curvature of the
      subsampled phase map. This local curvature is then low-pass filtered with a free
      boundary low-pass filter to reduce phase noise. Finally the estimated local
      curvature of the wave front is integrated by the use of a least-squares technique
      to obtain the searched continuous wave front.

PMID- 21085285
TI  - Interferometer for measuring the absolute refractive index of liquid water as a
      function of temperature at 1.064 um.
AB  - I describe here a new simple method for measuring the absolute refractive index
      of liquid water as a function of temperature at a wavelength of 1.064 um with a
      Michelson interferometer. The mirror of the measuring arm is located in a water
      cell and displaced by a well-known distance. Compensation for a change in the
      optical path length in the reference arm of the interferometer is not necessary.

PMID- 21085286
TI  - Design of single-element laser-beam shape projectors.
AB  - The design and fabrication of several single-element laser-beam projectors are
      described. These projectors take a Gaussian laser beam and expand it into a
      uniform intensity diverging shape, which can be either a single line, circle,
      cross, star, or a D. Each element consists of a single segmented surface designed
      so as to produce the required projected shape.

PMID- 21085287
TI  - Application of the see-saw method to all refracting optical systems.
AB  - The optical see-saw diagram is a method that describes image correction to third
      order approximation over a finite field of view in rotationally symmetric systems
      that employ aspheric surfaces. The aim of this paper is to describe the
      correction of aberrations caused by plane surfaces in all refracting optical
      systems in terms of the see-saw diagram. A lens correction algorithm based on the
      see-saw method is described to correct analytically the Seidel aberrations,
      primary spherical aberration, coma, astigmatism, and distortion, in such systems.
      We then apply this lens correction algorithm to the design of equivalent
      configurations by aspherizing different surfaces of the system, and the high
      order aberrations of the equivalent configurations are evaluated by means of
      transverse-ray-aberration plots. Results indicate that this method gives
      information on what the contribution must be to the third-order aberrations that
      each component should provide to the system to give a better balance of high
      order aberrations. Examples of the lens correction algorithm applied to lenses
      with six refracting surfaces and working for both finite and infinite object
      conjugates are given.

PMID- 21085288
TI  - Tailored reflectors for illumination.
AB  - We report on tailored reflector design methods that allow the placement of
      general illumination patterns onto a target plane. The use of a new integral
      design method based on the edge-ray principle of nonimaging optics gives much
      more compact reflector shapes by eliminating the need for a gap between the
      source and the reflector profile. In addition, the reflectivity of the reflector
      is incorporated as a design parameter. We show the performance of design for
      constant irradiance on a distant plane, and we show how a leading-edge-ray method
      may be used to achieve general illumination patterns on nearby targets.

PMID- 21085289
TI  - Dimensional stability tests over time and temperature for several low-expansion
      glass ceramics.
AB  - The dimensional stabilities of five commercially available low-expansion glass
      ceramics have been measured between -40  degrees C and +90  degrees C. Materials
      tested include Zerodur, Zerodur M, Astrositall, Clearceram 55, and Clearceram 63.
      With the use of a standardized thermal testing procedure, the thermal expansion,
      isothermal shrinkage, and hysteresis behavior of the various materials are
      compared with one another. A detailed comparison of three separate melts of
      Astrositall, two separate melts of Zerodur, and one melt of Zerodur M indicates
      that between -40  degrees C and +90  degrees C the dimensional stability and
      uniformity characteristics of two of the melts of Astrositall are somewhat better
      than those of the other two materials. To my knowledge, this is the first
      published comparison of data from these glass ceramics taken with identical test
      procedures.

PMID- 21085290
TI  - Portable Fourier transform infrared spectroradiometer for field measurements of
      radiance and emissivity.
AB  - A hand-held, battery-powered Fourier transform infrared spectroradiometer
      weighing 12.5 kg has been developed for the field measurement of spectral
      radiance from the Earth's surface and atmosphere in the 3-5-um and 8-14-um
      atmospheric windows, with a 6-cm(-1) spectral resolution. Other versions of this
      instrument measure spectral radiance between 0.4 and 20 um, using different
      optical materials and detectors, with maximum spectral resolutions of 1 cm(-1).
      The instrument tested here has a measured noise-equivalent delta T of 0.01 
      degrees C, and it measures surface emissivities, in the field, with an accuracy
      of 0.02 or better in the 8-14-um window (depending on atmospheric conditions),
      and within 0.04 in accessible regions of the 3-5-um window. The unique, patented
      design of the interferometer has permitted operation in weather ranging from 0 to
      45  degrees C and 0 to 100% relative humidity, and in vibration-intensive
      environments such as moving helicopters. The instrument has made field
      measurements of radiance and emissivity for 3 yr without loss of optical
      alignment. We describe the design of the instrument and discuss methods used to
      calibrate spectral radiance and calculate spectral emissivity from radiance
      measurements. Examples of emissivity spectra are shown for both the 3-5-um and 8
      14-um atmospheric windows.

PMID- 21085291
TI  - Determination of refractive index and thickness of thick transparent films by
      variable-angle spectroscopic ellipsometry: application to benzocyclobutene films.
AB  - An analysis procedure for evaluating the refractive index and the thickness of 5
      10-um-thick transparent films has been developed based on variable-angle
      spectroscopic ellipsometry. As an example of application, results from an
      analysis of benzocyclobutene films are presented. The sensitivities in psi and
      Delta with respect to the refractive index and the thickness of the films are
      also discussed.

PMID- 21085292
TI  - Diffraction efficiency of echelles working in extremely high orders.
AB  - Aproposal to use a high-angle echelle in the vacuum UV in the 350th order
      triggered a theoretical study to determine if there were unusual obstacles to
      success. No serious obstacles were found except for efficiency limitations.

PMID- 21085293
TI  - Analysis of the viewing zone of the Cambridge autostereoscopic display.
AB  - The Cambridge autostereoscopic three-dimensional display is a time-multiplexed
      device that gives both stereo and movement parallax to the viewer without the
      need for any special glasses. This analysis derives the size and position of the
      fully illuminated, and hence useful, viewing zone for a Cambridge display. The
      viewing zone of such a display is shown to be completely determined by four
      parameters: the width of the screen, the optimal distance of the viewer from the
      screen, the width over which an image can be seen across the whole screen at this
      optimal distance, and the number of views. A display's viewing zone can thus be
      completely described without reference to the internal implementation of the
      device. An equation that describes what the eye sees from any position in front
      of the display is derived. The equations derived can be used in both the analysis
      and design of this type of time-multiplexed autostereoscopic display.

PMID- 21085294
TI  - Optimizing the constant-channel chromaticity and color gamut of CRT color
      displays by control of brightness and contrast levels.
AB  - Before a CRT color display is calibrated, the levels of the brightness and
      contrast controls should be considered. These levels have different effects on
      the relationship between the chromaticity coordinates of the red-green-blue (RGB)
      channels and the voltage applied to the gun as well as on the color gamut. Using
      three different CRT color displays, we measured both these relationships as well
      as the color gamut for different combinations of brightness and contrast levels.
      With respect to the luminance range of the white point provided by each display,
      the results show that the assumption of constant-channel chromaticity of the RGB
      channels is more valid at medium- to low-brightness levels in combination with
      high-contrast levels. In addition, this assumption holds at high contrast and
      medium- to low-brightness levels, the color gamut being optimized at these
      combinations of levels, with regard to the size of the triangle of primaries-the
      maximum luminance of the display white point.

PMID- 21085295
TI  - Calibration standard for laser beam profilers: method for absolute accuracy
      measurement with a Fresnel diffraction test pattern.
AB  - The absolute accuracy of a clip-level laser beam profiler is measured to the 0.3%
      level, by comparison of the profiler's reading to the known width of a Fresnel
      diffraction test pattern. A pair of opposed knife edges, illuminated by a quasi
      uniform and quasi-plane wave, generates the pattern whose width is determined by
      the 50% cut points in translating the edge pair across a tightly focused beam.
      The convolution of the scanning aperture with the diffraction fringe pattern is
      modeled to remove the effect of the aperture size from the accuracy test and to
      give a means of measuring the aperture width. Discussions of the experimental
      aspects of this test method show it to be an acceptable calibration standard for
      optical profilers, of use to those working on the International Standards
      Organization draft standard for laser beam parameter measurements.

PMID- 21085296
TI  - Monte Carlo calculation of backscattered light intensity by suspension:
      comparison with experimental data.
AB  - An optical device for measuring high particle concentrations is presented. The
      sensor consists of two optical fibers used for the emission and reception of the
      light scattered by particles in suspension. To describe the light path in this
      medium, we developed a Monte Carlo calculation including a mean free path, a
      phase function for particle scattering, and an absorption rate. A similarity law
      links concentration variations to a homothetic space transformation. A comparison
      between our calculation and experimental data is given for well-stirred, dense
      suspensions of silica particles with different sizes. A good fit is found when
      the model parameters (mean free path and phase function) are chosen according to
      the data given by a particle sizer.

PMID- 21085297
TI  - Performance of ion-figured silicon carbide SUMER telescope mirror in the vacuum
      ultraviolet.
AB  - Measured and theoretical encircled energy and small-angle scatter of the
      telescope mirror (SST) of the solar ultraviolet measurements of emitted radiation
      (SUMER) instrument are compared at the wavelength of 123.6 nm. Mirror performance
      modeling was accomplished with the Optical Surface Analysis Code software
      package. The modeling is based on measured mirror-surface figure error data and
      roughness characteristics covering all important spatial frequencies that affect
      imaging in the vacuum ultraviolet wavelength region. Mirror-surface errors were
      measured with a Zygo Mark IV interferometer, Bauer Model 200 Profiler, and WYKO
      Topo 2-D (two-dimensional) interferometer. Performance of the SST mirror,
      including encircled energy and small-angle scatter, was also directly measured. A
      good agreement is found between measured and theoretical encircled energy within
      6 arcsec and small-angle scatter up to ~50 arcmin from the peak. The 80%
      encircled energy diameter of the SST mirror is ~1.9 arcsec, and the amount of
      scattered light drops to approximately 1.0 * 10(-10) of peak irradiance
      (normalized to 1 arcsec(2) in the focal plane) 50 arcmin from the peak. Vacuum
      ultraviolet performance of the mirror is degraded primarily by midfrequency
      errors.

PMID- 21085298
TI  - Laboratory simulation of a turbulent layer: optical and in situ characterization.
AB  - Up to now only a few numerical or experimental simulations of atmospheric
      turbulent layers have been performed in the laboratory. These are devoted mainly
      to show the validity of Kolmogorov behavior but are not suitable to implement in
      an optical bench to test light propagation. Here we present a small size
      experimental simulation of an optical turbulent layer. With optical and in situ
      measurements, we managed to determine its characteristics: the mean variance of
      the refractive-index fluctuations integrated over the thickness of the turbulent
      flow and longitudinal and transverse structure functions of angles of arrival.
      From these measurements we found that the power spectrum of the refractive index
      is well fitted by a Von Karman function with an outer scale of 91 mm and an inner
      scale of 4.7 mm. Moreover, the temporal stationarity of these parameters
      indicates the reproducibility of this simulated turbulent flow.

PMID- 21085299
TI  - Clinical determination of tissue optical properties by endoscopic spatially
      resolved reflectometry.
AB  - A noninvasive method to measure the optical properties of a diffusing and
      absorbing medium is described. Based on the spatially resolved measurement of
      diffuse reflectance at the sample surface, this method is particularly suitable
      for investigating the in vivo optical properties of biological tissues
      endoscopically in a clinical context. The sensitivity of the measurement is
      discussed, and two optical probes for two different clinical applications are
      presented. Preliminary measurements are performed on a nonbiological medium,
      which illustrate the possibilities of the proposed method. Finally, we report on
      in vivo measurements of the optical properties of the human esophageal wall at
      630 nm.

PMID- 21085300
TI  - Absorptivity contrast in transillumination imaging of tissue abnormalities.
AB  - We calculate the time-resolved flux of photons transmitted across an optically
      turbid slab containing a partially absorbing inclusion. An analytical expression
      is obtained for the flux at a detector positioned opposite a point source (at a
      distance equal to the thickness of the slab) when the center of the inclusion
      lies on the line connecting those points. The calculation employs a discrete-time
      lattice random-walk model of photon transport. The resulting expression is used
      to assess the affects of time resolution on the detectability of the inclusion.

PMID- 21085301
TI  - Biological laser action.
AB  - The narrowing of the spectral linewidth and the increasing of the peak intensity
      characteristic of laser action were observed in emission spectra of dye-infused
      biological tissues. The tissue was infused with a solution of Rhodamine 640
      perchlorate in ethanol and then excited with frequency-doubled Q-switched Nd:YAG
      laser pulses. The dependence of emission linewidth on the excitation radiant
      exposure and dye concentration was investigated. Laser action was also observed
      in biologically compatible fluorescein sodium dye dissolved in phosphate-buffered
      saline mixed with scattering polystyrene spheres. The sharp spectral peaks of
      laser action in tissues may find applications in the detection of superficial
      disease.

PMID- 21085302
TI  - Fluorescence spectroscopy of tissue: recovery of intrinsic fluorescence from
      measured fluorescence.
AB  - We present a method for recovering the intrinsic fluorescence coefficient,
      defined as the product of the fluorophore absorption coefficient and the
      fluorescence energy yield, of an optically thick, homogeneous, turbid medium from
      a surface measurement of fluorescence and from knowledge of medium optical
      properties. The measured fluorescence signal is related to the intrinsic
      fluorescence coefficient by an optical property dependent path-length factor. A
      simple expression was developed for the path-length factor, which characterizes
      the penetration of excitation light and the escape of fluorescence from the
      medium. Experiments with fluorescent tissue phantoms demonstrated that intrinsic
      fluorescence line shape could be recovered and that fluorophore concentration
      could be estimated within +/-15%, over a wide range of optical properties.

PMID- 21085303
TI  - Measurement method of the refractive index of biotissue by total internal
      reflection.
AB  - A simple method based on total internal reflection is presented for measuring the
      refractive index of biological tissue. Anarrow laser beam and a semicylindrical
      lens in contact with a tissue specimen are used in the experimental apparatus.
      The dependence of the internal reflectivity on the angle of incidence is measured
      to determine the critical angle and therefore the refractive index of tissue. The
      experimental results for several tissue samples show that the method is reliable
      and useful for studying tissue optics. The principal advantages of the method are
      its elimination of scattering effects, suitability to a small in vitro sample,
      and excellent accuracy.

PMID- 21085304
TI  - Photon-noise limits to the detection of the closure phase in optical
      interferometry.
AB  - Michelson stellar interferometers with long baselines have been proposed as a
      means for obtaining high-resolution images of space objects. The fringes measured
      in such interferometers move randomly owing to atmospheric turbulence effects.
      For overcoming turbulence effects the fringe phase at any instant is summed
      around groups of three or more aperture pairs to create the so-called closure
      phase. The closure phase is insensitive to atmospheric turbulence effects;
      however, it is corrupted by photon-noise effects. The probability-density
      function of the error in the closure-phase estimate that is due to photon noise
      is derived as a function of the fringe visibility and is evaluated. It is shown
      that, for dim objects and low fringe visibility, several hundred to several
      thousand independent realizations of the closure phase must be averaged to obtain
      acceptable closure-phase variance.

PMID- 21085305
TI  - Shearing interferometer with a Kitty self-pumped phase-conjugate mirror.
AB  - A shearing interferometer with a Kitty-type self-pumped phase-conjugate mirror is
      developed. The measurement of the focal length of a lens is demonstrated with a
      standard deviation of 1.5%. In addition, we measured the microdisplacement in the
      range of tens of micrometers with an error less than 2% by using the
      interferometer.

PMID- 21085306
TI  - Multilayer array illuminators with binary phase plates at fractional Talbot
      distances.
AB  - We describe a Talbot array illuminator made of cascaded binary phase plates
      located at fractional Talbot distances. We compare the performance of such an
      illuminator with a conventional single-layer Talbot array illuminator in terms of
      compression ratio and technical feasibility.

PMID- 21085307
TI  - Area-time trade-offs in arrays with optical pipelined buses.
AB  - A general model for determining the computational efficiency of a particular
      class of electro-optical systems is described. The model is an abstraction of
      parallel systems that use digital electronic processors and optical pipelined
      buses for communication. Minimum requirements in terms of area (volume for three
      dimensional structures) and time necessary in order to solve a problem are
      obtained. Different applications are investigated, and a matching area-time upper
      bound is given for the barrel-shift problem, simulated on an array with
      reconfigurable optical pipelined buses. The types of problems for which these
      lower bounds seem to be realistic are described.

PMID- 21085308
TI  - Time multiplexing and control for optical cellular-hypercube arrays.
AB  - We discuss the cellular-hypercube optical free-space interconnection architecture
      and its implementation by two-dimensional smart-pixel optoelectronic cellular
      arrays. We emphasize the behavior of the cellular hypercube in performing shift
      invariant parallel shifts of data, a basic requirement of most single-instruction
      multiple-data algorithms. We present a time-multiplexing scheme for realizing the
      cellular hypercube, showing that the communication time is inversely proportional
      to the number of optical detectors per cell. We also present an improved hybrid
      interconnection network with improved performance that combines the cellular
      hypercube and mesh, using optics for the longer-distance connections and
      electronics for nearest-neighbor connections.

PMID- 21085309
TI  - Spatial light modulation based on photoinduced change in the complex refractive
      index of bacteriorhodopsin.
AB  - Bacteriorhodopsin exhibits photoinduced changes in both absorption and refractive
      index at 633 nm. To explore the possibility of exploiting this property in
      constructing a photoaddressed spatial light modulator, we investigated the
      transmission property of a Fabry-Perot interferometer containing a
      bacteriorhodopsin thin film. Film was formed that had a phase shift of pi/4 and
      sufficient interference fringe contrast for spatial light modulation. This
      establishes the possibility of constructing a spatial light modulator that
      features nonlinear input-output characteristics and can operate at moderate light
      intensities of the order of tens of milliwatts per centimeter square.

PMID- 21085310
TI  - Target detection in optically scattering media by polarization-difference
      imaging.
AB  - Polarization-difference imaging (PDI) was recently presented by us as a method of
      imaging through scattering media [Opt. Lett. 20, 608 (1995)]. Here, PDI is
      compared with conventional, polarizationblind imaging systems under a variety of
      conditions not previously studied. Through visual and numerical comparison of
      polarization-difference and polarization-sum images of metallic targets suspended
      in scattering media, target features initially visible in both types of images
      are shown to disappear in polarization-sum images as the scatterer concentration
      is increased, whereas these features remain visible in polarization-difference
      images. Target features producing an observed degree of linear polarization of
      less than 1% are visible in polarization-difference images. The ability of PDI to
      suppress partially polarized background variations selectively is demonstrated,
      and discrimination of target features on the basis of polarization information is
      discussed. Our results show that, when compared with conventional imaging, PDI
      yields a factor of 2-3 increase in the distance at which certain target features
      can be detected.

PMID- 21085311
TI  - Multiple circular-harmonic-function correlation filter providing specified
      response to in-plane rotation.
AB  - The circular-harmonic-function correlation filter originally proposed by Hsu and
      Arsenault [Appl. Opt. 21, 4016 (1982)] for in-plane rotation invariance uses only
      one harmonic, which results in poor discrimination capability of the filter.
      Various methods to use multiple harmonics were explored previously by different
      researchers. We present a new method to combine multiple circular harmonics into
      a single filter that can provide the desired correlation response to in-plane
      rotation while minimizing the correlation-plane energy. Since multiple harmonics
      are included, the filter can discriminate well, and since correlation-plane
      energy is minimized, correlation peaks tend to be sharp. Since the designer can
      specify the desired in-plane rotation response, a variety of filter behaviors
      (including complete invariance to input rotations) can be obtained. Underlying
      theory is discussed, and simulation results are presented.

PMID- 21085312
TI  - Image preprocessing for rotation-invariant pattern recognition in the presence of
      signal-dependent noise.
AB  - I propose a new method that ensures efficient rotation-invariant pattern
      recognition in the presence of signal-dependent noise by combining the
      application of rotation-invariant correlation filters with preprocessing of the
      noisy input images. The preprocessing uses local suboptimal estimators derived
      from estimation theory and implies an a priori knowledge of a model describing
      the noise source. The image noise sources considered are speckle and film-grain
      noise. Pour different metrics are used to analyze the correlation performance of
      the circular-harmonic filter, the phase-only circular-harmonic filter, and the
      binary phase-only circular-harmonic filter, with and without a preprocessing.
      Computer simulations show that signal-dependent noise can seriously degrade the
      performance of the phase-only circular-harmonic filter and the binary phase-only
      circular-harmonic filter. The most severe indication of correlation-performance
      degradation is the occurrence of false alarms in 15% to 20% of noise realizations
      of the correlation. Preprocessing increases the correlation-peak signal-to-noise
      ratio significantly and reduces the false-alarm probability by one to two orders
      of magnitude.

PMID- 21085313
TI  - Rotation- and scale-invariant feature extraction by a diffractive optical inner
      product transform.
AB  - A diffractive optical element that is capable of extracting rotation- and scale
      invariant features from input images is presented. The diffractive optical
      element performs an inner product between the input image and a set of basis
      functions. This set of basis functions is derived from that used in the Fourier
      Mellin transform. Simulated results from scaled and rotated versions of two input
      images are presented.

PMID- 21085314
TI  - Reduction in correlation-filter sensitivity to background clutter by the
      automatic spatial frequency selection algorithm.
AB  - We propose an automatic spatial frequency selection correlation filter that
      reduces the sensitivity to nonoverlapping noise or background clutter. This is
      achieved by inclusion of distorted versions of the reference images surrounded by
      nonoverlapping background clutter. Furthermore, we impose that the window
      functions of the reference images give response zero-correlation amplitudes.
      Simulation results are provided in the case of a two-class pattern-recognition
      problem and show that the results are appreciably increased. The results are
      compared with a normal automatic spatial frequency selection.

PMID- 21085315
TI  - Edge enhancement of a phase-conjugate image with a mutually pumped phase
      conjugator.
AB  - Usually edge enhancement of optical images is produced by introduction of loss
      into the low spatial frequency components of the image-bearing beam in the
      Fourier plane of a lens. We report on edge-enhanced phase-conjugate images from a
      mutually pumped conjugator accomplished by spatial filtering in the Fraunhofer
      diffraction region of the input beams. High-resolution (128-160 lines/mm) edge
      enhanced images are obtained through traditional spatial filtering in the Fourier
      plane and in the Fraunhofer regime. Amplification of these edge-enhanced images
      is observed with some loss of high spatial resolution (50 lines/mm).

PMID- 21085316
TI  - Power distribution in two-dimensional optical network channels.
AB  - The power distribution in two-dimensional optical network channels is analyzed.
      The maximum number of allowable channels as determined by the characteristics of
      optical detector is identified, in particular, for neural-network and wavelet
      transform applications.

PMID- 21085317
TI  - Improved method of exponential sum fitting of transmissions to describe the
      absorption of atmospheric gases.
AB  - For climate modeling and atmospheric research, such as investigations of global
      climate change, remote sensing of cloud properties, or the missing absorption
      problem in clouds, it is most important to describe adequately the absorption of
      radiation by atmospheric gases. An improved method for the exponential sum
      fitting of transmissions (ESPT) is developed to approximate this absorption
      accurately. Exponentials are estimated separately for any number of atmospheric
      model layers, considering the pressure and temperature dependence of the
      absorption lines directly. As long as the error of the fit exceeds a limit of
      tolerance, the number of considered exponential terms is successively increased.
      The accuracy of the method presented yields a root-mean-square error of less than
      0.03% for any atmospheric-model layer, whereas the commonly used one-layer
      techniques gain errors of up to 3% in the transmission functions for the upper
      layers. The commonly used ESPT methods consider only one atmospheric layer and
      introduce the pressure and temperature effects for the other model layers
      afterward.

PMID- 21085318
TI  - Infrared absorption by methane isotopes near 2999 cm(-1): an analytical method
      using the Zeeman split He-Ne laser line at 2999.24 cm(-1).
AB  - We report the strengths and locations of the absorption lines of CH(3)D,
      (13)CH(4), and (12)CH(4) in the vicinity of the helium-neon laser line at 2999.24
      cm(-1). In this region we find intrinsically strong lines of the rare species
      overlapping, but not precisely coincident with, intrinsically weak lines of the
      major species. In methane of normal isotopic composition, the lines of all three
      species have comparable strengths. We show how absorption measurements of the He
      Ne laser, with Zeeman splitting, can be used to determine variations of the
      concentrations of the rare species from standard concentrations at a calculated
      precision of 0.5%0.

PMID- 21085319
TI  - Ellipsometry of diffractive insect reflectors.
AB  - Scales on the wings of certain insects, such as Trichoplusia orichalcea, exhibit
      a surface micro structure resembling a fine diffraction grating. Diffraction of
      incident light by this structure is responsible for many of the optical
      properties of the wings of this moth, such as the metallic yellow color and the
      almost-specular reflection and polarization properties of the scattered
      radiation. It is shown that by the use of null ellipsometry the polarization
      characteristics can be used to obtain the optical constants of the scale
      material. Theoretical considerations and suitable experimental conditions are
      discussed and evaluated.

PMID- 21085320
TI  - Avalanche photodiodes and quenching circuits for single-photon detection.
AB  - Avalanche photodiodes, which operate above the breakdown voltage in Geiger mode
      connected with avalanche-quenching circuits, can be used to detect single photons
      and are therefore called singlephoton avalanche diodes SPAD's. Circuit
      configurations suitable for this operation mode are critically analyzed and their
      relative merits in photon counting and timing applications are assessed. Simple
      passive-quenching circuits (PQC's), which are useful for SPAD device testing and
      selection, have fairly limited application. Suitably designed active-quenching
      circuits (AQC's) make it possible to exploit the best performance of SPAD's.
      Thick silicon SPAD's that operate at high voltages (250-450 V) have photon
      detection efficiency higher than 50% from 540- to 850-nm wavelength and still ~3%
      at 1064 nm. Thin silicon SPAD's that operate at low voltages (10-50 V) have 45%
      efficiency at 500 nm, declining to 10% at 830 nm and to as little as 0.1% at 1064
      nm. The time resolution achieved in photon timing is 20 ps FWHM with thin SPAD's;
      it ranges from 350 to 150 ps FWHM with thick SPAD's. The achieved minimum
      counting dead time and maximum counting rate are 40 ns and 10 Mcps with thick
      silicon SPAD's, 10 ns and 40 Mcps with thin SPAD's. Germanium and III-V compound
      semiconductor SPAD's extend the range of photon-counting techniques in the near
      infrared region to at least 1600-nm wavelength.

PMID- 21085321
TI  - Laser with a nonlinear mirror: application for improving the output power
      stability of a cw laser.
AB  - We put forward a new method for improving the output power stability of a cw
      laser. The basic idea is to replace the output mirror of a laser with a nonlinear
      mirror that is formed by a dispersive nonlinear Fabry-Perot etalon. Based on the
      semiclassical dynamic model for this system, first we derive the static
      conditions for this laser operating with stabilized output power, then we study
      the dynamic responses of output power to gain fluctuations. Both static and
      dynamic results show that, compared with normal lasers, the output power
      stability of our laser can be improved significantly when the output power
      fluctuations are caused by the fluctuations of the gain. The improvement of the
      output power can be explained by the fact that there exists an optical servoloop
      in this laser that is produced by the nonlinear mirror.

PMID- 21085322
TI  - High heat-dissipation-efficiency discharge tube for ion lasers with an Al(2)O(3)
      ceramic-copper sandwich structure.
AB  - A high heat-dissipation-efficiency discharge tube for ion lasers is discussed and
      compared with conventional tube structures. The results show that the capability
      to dissipate heat of this Al(2)O(3) ceramic-copper sandwich structure tube is
      better than that of the BeO ceramic tube and the water-cooled Al(2)O(3) ceramic
      tungsten tube. An air-cooled argon laser constructed with this structure has been
      operating for over 2000 h.

PMID- 21085323
TI  - Photonic textile fibers.
AB  - The characterization of the emission from nylon fibers containing laser dyes and
      TIO(2) nanoparticle scatterers indicates laser behavior with linewidths as low as
      4 nm in 200- to 800-um fibers. These materials can be used to produce lasing
      textiles, which can be used to produce photonic codes for a variety of civilian
      and military applications.

PMID- 21085324
TI  - Dual-wavelength operation of a self-seeded dye laser oscillator.
AB  - We demonstrate simultaneous dual-wavelength operation of a self-seeded dye laser.
      The laser cavity consists of one dye cell, two pairs of grating and tuning
      mirrors, and two reflecting mirrors. This configuration can be decomposed with
      two grazing-incidence cavities and a standing-wave cavity. The self-seeded dual
      wavelength output beams are collinear and independently tunable. We were able to
      vary the output powers at the two wavelengths smoothly by changing the cavity
      length of a master oscillator.

PMID- 21085325
TI  - Pulsed Ti:sapphire laser seeded off the gain peak.
AB  - An external-cavity diode laser is used to seed a pulsed Ti:sapphire laser from
      839 to 860 nm. Because this wavelength range is off the gain peak of Ti:sapphire,
      a bandpass filter is used in the cavity to permit seeded operation. We describe a
      tunable, wide-field-of-view birefringent filter especially suited for use in
      seeded lasers. Measurements of the ratio of unseeded to seeded output as a
      function of seed power are also presented and demonstrate an approximately
      reciprocal dependence on the seed power.

PMID- 21085326
TI  - Theory and optimization of lens ducts.
AB  - Lens ducts are simple optical devices that have found application in the coupling
      of pump radiation from extended two-dimensional semiconductor laser diode arrays
      into solid-state laser gain media. The operation of these devices relies on the
      combined effects of lensing at their curved input surface and channeling by total
      internal reflection off their canted planar sides, to contain and couple
      semiconductor diode laser light efficiently to the input face of a solid-state
      laser crystal or glass. The lens duct provides a robust method for amplifying the
      irradiance of laser diode array pump sources and has made possible a scalable
      diode end-pumping architecture that offers the opportunity to expand
      significantly the number of ions and transitions that can be practically engaged
      in diode-pumped solid-state laser systems. An analytic model that describes the
      transfer efficiency of lens ducts and aids in the optimization of their design is
      presented.

PMID- 21085327
TI  - Optical feedback effects in Nd-doped fiber lasers with broadband spectra.
AB  - A detailed experimental and theoretical investigation of optical feedback effects
      in Nd-doped fiber lasers is presented. Of particular interest is an output
      intensity reduction attributed to the broadband nature of the laser spectrum
      combined with a mode-selection mechanism of the external Fabry-Perot cavity. The
      theoretical approach, based on a simple multimode rate-equation model, provides
      an excellent description of the experimental results.

PMID- 21085328
TI  - Laser demonstration of diode-laser-pumped neodymium-doped strontium
      fluorovanadate.
AB  - The laser properties of diode-laser-pumped neodymium-doped strontium
      fluorovanadate samples cut perpendicular to the x(a) and y axes have been
      investigated. A slope efficiency of 36% for the 1.065-um laser line and a lasing
      threshold of 6.8 mW have been measured for the x(a)-axis-cut crystal. Data are
      also presented for the laser's performance as a function of crystal temperature
      and for the variation of the central peak wavelength with the incident pump
      power.

PMID- 21085329
TI  - Regenerative amplification of femtosecond pulses at 745 nm in Ti:sapphire.
AB  - A regenerative amplifier for femtosecond pulses that operates at a wavelength off
      the peak gain of Ti:sapphire is reported. Apair of prisms and an adjustable slit
      are used in the intracavity space so that the operating wavelength can be tuned
      to 745 nm. The amplified and compressed pulse is 92 fs (Gaussian profile assumed)
      at an energy of 1 mJ. The pumping efficiency is 12.5%.

PMID- 21085330
TI  - Fluorescence and phase-conjugated signals of organic materials.
AB  - The role of fluorescence has not always been fully understood in optical
      engineering experiments that are devoted to the generation of phase-conjugated
      waves from organic materials. It is pointed out that fluorescence can appear if
      the material absorbs at the wavelength of the excitation. Therefore proper
      experimental precautions should be taken in the detection of the intrinsic phase
      conjugated signal.

PMID- 21085331
TI  - Absolute measurement of the effective nonlinearities of KTP and BBO crystals by
      optical parametric amplification.
AB  - Absolute magnitudes of the effective nonlinearity, deff, were measured for seven
      KTP and six BBO crystals. The d(eff), were derived from the parametric gain of an
      800-nm signal wave in the sample crystals when they were pumped by the frequency
      doubled, spatially filtered light from an injectionseeded, Q-switched Nd:YAG
      laser. The KTP crystals, all type II phase matched with propagation in the X-Z
      plane, had d(eff) values ranging from 1.97 to 3.50 pm/V. Measurements of gain as
      a function of phase velocity mismatch indicate that two of the KTP crystals
      clearly contain multiple ferroelectric domains. For five type I phase-matched BBO
      crystals, d(eff) ranged from 1.76 to 1.83 pm/V, and a single type II phase
      matched BBO crystal had a d(eff) of 1.56 pm/V. The uncertainty in our
      measurements of d(eff) values is +/-5% for KTP and +/-10% for BBO.

PMID- 21085332
TI  - Accurate expressions for the LP modes in a uniform circular-core curved fiber.
AB  - Accurate forms for the LP(nm) modes (n = 0 and n ? 2) in a uniform circular-core
      curved fiber are given. We show that the LP(nm) modes (n ? 2) are composed of two
      spatially orthogonal components and that, to the zeroth order, there is no
      special polarization axis for the LP modes in a uniform circular-core curved
      fiber.

PMID- 21085333
TI  - Optimum refractive-index profile of the graded-index polymer optical fiber,
      toward gigabit data links.
AB  - The optimum refractive-index distribution of the high-bandwidth graded-index
      polymer optical fiber (POP) was clarified for the first time by consideration of
      both modal and material dispersions. The ultimate bandwidth achieved by the POP
      is investigated by a quantitative estimation of the material dispersion as well
      as the modal dispersion. The results indicate that even if the refractive-index
      distribution is tightly controlled, the bandwidth of the graded-index POP is
      dominated by the material dispersion when the required bit rate becomes larger
      than a few gigabits per second. It is also confirmed that the material dispersion
      strongly depends on the matrix polymer and that the use of a fluorinated polymer
      whose material dispersion [-0.078 ns/(nm km)] is lower than that of poly(methyl
      methacrylate) [-0.305 ns/(nm km)] allows for a 10-Gb/s signal transmission.

PMID- 21085334
TI  - Theory of reflectivity of an asymmetric mirror.
AB  - By using the concept of transfer matrices and Bloch waves, we have derived a set
      of equations that provide insight into the operation of asymmetric Bragg
      reflectors that have been demonstrated to be useful in achieving high
      reflectivities in strained-material systems. These equations will be useful in
      the design of asymmetric mirrors and can be used to compare the trade-offs
      between the conventional, symmetric (quarter-wavelength), and asymmetric mirrors.

PMID- 21085335
TI  - Improved propagation-mode near-field method for refractive-index profiling of
      optical waveguides.
AB  - Experimental and theoretical improvements to the propagation-mode near-field
      technique for refractive-index profiling have been made. The measured near-field
      profile is deconvoluted with the transfer function of the optical imaging system
      in order to recover the actual near-field profile. Anew equation is also derived
      in order to use these data to reconstruct the refractive-index profile of the
      waveguide under consideration. The improved method, which is valid for all
      relevant wavelength ranges, is demonstrated in the determination of the
      refractive-index profiles of two single-mode planar waveguides.

PMID- 21085336
TI  - Low-power resonant laser ablation of copper.
AB  - We emphasize two points: (l) the properties and mechanisms of very low-fluence
      ablation of copper surfaces and (2) the sensitivity and selectivity of resonant
      laser ablation (RLA). We present results for ablation of bulk copper and copper
      thin films; spot-size effects; the effects of surface-sample preparation and beam
      polarization; and an accurate measurement of material removal rates, typically <=
      10(-3) A at 35 mJ/cm(2). Velocity distributions were Maxwellian, with peak
      velocities ~ 1-2 * 10(5) cm/s. In addition, we discuss the production of
      diffractionlike surface features, and the probable participation of nonthermal
      desorption mechanisms. RLA is shown to be a sensitive and useful diagnostic for
      studies of low-fluence laser-material interactions.

PMID- 21085337
TI  - Signal processing and calibration of continuous-wave focused CO(2) Doppler lidars
      for atmospheric backscatter measurement.
AB  - Two continuous-wave (CW) focused CO(2) Doppler lidars (9.1 and 10.6 um) were
      developed for airborne in situ aerosol backscatter measurements. The complex path
      of reliably calibrating these systems, with different signal processors, for
      accurate derivation of atmospheric backscatter coefficients is documented. Lidar
      calibration for absolute backscatter measurement for both lidars is based on
      range response over the lidar sample volume, not solely at focus. Both lidars
      were calibrated with a new technique using well-characterized aerosols as
      radiometric standard targets and related to conventional hard-target calibration.
      A digital signal processor (DSP), a surface acoustic wave spectrum analyzer, and
      manually tuned spectrum analyzer signal analyzers were used. The DSP signals were
      analyzed with an innovative method of correcting for systematic noise
      fluctuation; the noise statistics exhibit the chi-square distribution predicted
      by theory. System parametric studies and detailed calibration improved the
      accuracy of conversion from the measured signal-to-noise ratio to absolute
      backscatter. The minimum backscatter sensitivity is ~3 * 10(-12) m(-1) sr(-1) at
      9.1 um and ~9 * 10(-12) m(-1) sr(-1) at 10.6 um. Sample measurements are shown
      for a flight over the remote Pacific Ocean in 1990 as part of the NASA Global
      Backscatter Experiment (GLOBE) survey missions, the first time to our knowledge
      that 9.1-10.6-um lidar intercomparisons were made. Measurements at 9.1 um, a
      potential wavelength for space-based lidar remote-sensing applications, are to
      our knowledge the first based on the rare isotope (12)C (18)O(2) gas.

PMID- 21085338
TI  - Lidar calibration technique using laboratory-generated aerosols.
AB  - A new calibration technique for continuous-wave Doppler lidars that uses an
      aerosol scattering target has been developed. Calibrations with both single- and
      many-particle scattering were performed at the same lidar operating conditions as
      in atmospheric measurements. The calibrating targets, simulating atmospheric
      aerosols, were laboratory-generated spherical silicone oil droplets with known
      complex refractive indices and sizes, hence with known single-particle
      backscatter cross sections as obtained from Mie theory. Measurements of lidar
      efficiency with the conventional hard target calibration method were consistently
      higher by a factor of ~2 than measurements with the aerosol calibration
      technique. This result may have important implications for lidar backscatter
      estimates both for aerosol modeling efforts and for optimal design of future
      lidar systems. The aerosol calibration method provides a validation of basic
      lidar theory for particle scattering for coherent detection.

PMID- 21085339
TI  - Covariance of the absorption of phytoplankton, colored dissolved organic matter,
      and detritus in case I waters, as deduced from the Coastal Zone Color Scanner bio
      optical algorithm.
AB  - The universal bio-optical algorithm of the Coastal Zone Color Scanner (CZCS) for
      case I waters implicitly contains an average covariance of the absorption by
      phytoplankton and colored dissolved organic matter (CDOM) and detritus. We made
      that covariance explicit by combining the CZCS algorithm with an expression for
      reflectance. The spectral variation of absorption by CDOM plus detritus for case
      I waters may be estimated by the expression a(gd(lambda)) = 2a(ph)(443)*chl{exp[
      0.013(lambda - 443)].

PMID- 21085340
TI  - Spectral attenuation and aerosol particle size distribution.
AB  - The problem of the reconstruction of the spectrum of a dispersed system from data
      on its spectral attenuation is studied. The numerical algorithm for obtaining the
      particle size distribution by the use of the concept of regularization is
      thoroughly treated. The applicability of this method to the reconstruction of the
      particle size distribution of a typical marine aerosol is tested. A method of
      choosing the regularization parameter of the solution for the inverse problem
      based on an objective estimate of the validity of the obtained solution is
      proposed. Results are presented for a set of numerical experiments in which the
      radius interval for which the distribution function can be obtained with a
      satisfactory accuracy is estimated. The validity of solutions is estimated
      depending on the measuring spectral range for the attenuation, the radius
      interval, and the number and position of points within this interval. The
      possibility of extending the radius interval for which the distribution function
      can be obtained by the use of extrapolation of the distribution function tail is
      discussed.

PMID- 21085341
TI  - Measurements of hydroxyl concentrations and lifetimes in laminar flames using
      picosecond time-resolved laser-induced fluorescence.
AB  - Picosecond time-resolved laser-induced fluorescence (PITLIF) can potentially be
      used to obtain measurements of minor species concentrations in rapidly
      fluctuating flames. Previous studies demonstrated this potential for atomic
      sodium by monitoring the temporal fluorescence signal with both an equivalent
      time and a real-time sampling method. In this developmental study, PITLIF is used
      to determine hydroxyl concentrations in laminar CH(4)-O(2)-N(2) flames by the
      measurement of both the integrated fluorescence signal and the fluorescence
      lifetime. The quenching environment can be monitored with real-time sampling, and
      thus the necessary quenching rate coefficient is obtained in 348 us, which is
      fast enough for use in many turbulent flows. Fluorescence lifetimes of OH are
      also measured at different equivalence ratios in laminar flames by the use of the
      equivalent-time sampling technique. These results compare favorably with
      predicted lifetimes based on relevant quenching cross sections and calculated
      species concentrations.

PMID- 21085342
TI  - Investigation of NO detection in flames by the use of polarization spectroscopy.
AB  - Various aspects of detection of NO molecules in a premixed H(2)/N(2)O flame were
      investigated by the use of polarization spectroscopy. The signals were recorded
      in the A(2)Sigma(+)-X(2)II (0, 0) band of NO at 226 nm. Excitation spectra for
      circularly and linearly polarized pump beams are presented to illustrate the
      influence of the polarization state. The signal dependencies on the pump- and the
      probe-beam intensities were also investigated, as well as the influence of the
      setup geometry with respect to the pump-beam focusing and the crossing angle
      between the pump and the probe beams. A preliminary evaluation of temperature
      based on spectra recorded by the use of the Boltzmann plotting approach was
      performed. Finally the possibilities of two-dimensional imaging of the NO
      molecules were demonstrated.

PMID- 21085343
TI  - Range-finding by triangulation with nondiffracting beams.
AB  - Nondiffracting beams are useful for alignment applications because the size of
      the beam does not change as the beam propagates. In this research we report a
      technique that allows for distance measurements with nondiffracting beams. With
      our approach a diffractive optical element is designed that generates two off
      axis, tilted, nondiffracting Bessel function beams. These beams intersect at a
      desired distance from the input plane, producing interference. We generate these
      Bessel function arrays with a programmable spatial light modulator allowing
      external control over the intersection distance.

PMID- 21085344
TI  - Diffraction effects in the radiometry of coherent beams.
AB  - High-accuracy radiometry requires an optical beam in which all the light is
      contained within the radius of the smallest detector to be calibrated. We analyze
      a common configuration of the optical components used to prepare such a beam and
      show that diffraction rings are formed in the far field although the irradiance
      is zero along the limiting aperture's edge. The beam profile is calculated and
      used to find the radius of the smallest detector that can be calibrated with this
      beam.

PMID- 21085345
TI  - Refractive-index measurement of gradient-index microlenses by diffraction
      tomography.
AB  - Diffraction tomography is applied to reconstruction of the gradient-index
      distribution of planar gradient-index microlenses, fabricated by thermal ion
      exchange. Measurements of the single-phase projections are performed by phase
      shifting interferometry For reconstruction, the Rytov approximation for smooth
      inhomogeneities is applied. Results are compared with measurement results from
      other methods and simulation results.

PMID- 21085346
TI  - Numerical simulations of vibration in phase-shifting interferometry.
AB  - Computer simulations predict the expected rms measurement error in a phase
      shifting interferometer in the presence of mechanical vibrations. The simulations
      involve a numerical resolution of a nonlinear mathematical model and are
      performed over a range of vibrational frequencies and amplitudes for three
      different phase-shift algorithms. Experimental research with an interference
      microscope and comparison with analytical solutions verify the numerical model.

PMID- 21085347
TI  - Two-color interferometer for surface characterization using two frequency
      doublers and a four-phase-step method.
AB  - A high-accuracy, two-color interferometer for characterizing a processed surface
      is described. It is composed of two frequency doublers. It is not affected by air
      turbulence and mechanical vibration because it is a complete common-path
      interferometer, and the effects from different reflectivities of various
      materials are canceled by a four-phase-step technique that shifts the phase of
      the interference fringe in steps of pi/2. The processed surface is measured with
      subnanometer resolution.

PMID- 21085348
TI  - Numerical model estimating the capabilities and limitations of the fast Fourier
      transform technique in absolute interferometry.
AB  - Anumerical model was developed to emulate the capabilities of systems performing
      noncontact absolute distance measurements. The model incorporates known methods
      to minimize signal processing and digital sampling errors and evaluates the
      accuracy limitations imposed by spectral peak isolation by using Harming,
      Blackman, and Gaussian windows in the fast Fourier transform technique. We
      applied this model to the specific case of measuring the relative lengths of a
      compound Michelson interferometer. By processing computer-simulated data through
      our model, we project the ultimate precision for ideal data, and data containing
      AM-FM noise. The precision is shown to be limited by nonlinearities in the laser
      scan.

PMID- 21085349
TI  - Processing of interferometric phase maps as complex-valued phasor images.
AB  - Phase and amplitude information obtained from phase-shifting interferometry may
      be combined, to be a complex-valued phasor for every pixel of the image. Phasor
      image processing is presented as a simple yet effective concept for filtering,
      visualization, masking, and unwrapping interferometric phase maps. The results
      from two electronic speckle pattern interferometry data sets illustrate the new
      method.

PMID- 21085350
TI  - Optical angular properties of twisted-nematic liquid-crystal cells with twist
      angles of less than 90 degrees .
AB  - I analyze the optical angular properties of twisted-nematic liquid-crystal cells
      that operate in the normally white mode with twist angles of less than 90 degrees
      . It is demonstrated that, although a reduction of the twist angle produces an
      increase in the asymmetry of the birefringence generated by a single cell when in
      the active phase, the positioning of two cells such that the face-to-face rub
      directions are crossed gives rise to a large amount of cell compensation, giving
      an enhanced field of view. The effect of the polarizer arrangement is
      investigated, and it is shown that the configuration required in order to
      maximize the overall optical transmittance when in the inactive phase also
      maintains the asymmetry displayed by the single cell when stimulated by voltages
      lying below that of the saturation voltage. Although employment of this polarizer
      design together with a lowering of the twist angle degrades cell contrast, a fast
      optical shutter from the light to the dark state based on a double-cell
      construction possessing improved optical angular properties is introduced. Such
      systems find applications in automatically darkening welding filter visors for
      which it is critical to combine both a fast response time to the protective state
      together with a large viewing cone.

PMID- 21085351
TI  - Analysis of polarization properties of a mode-locked fiber laser gyroscope.
AB  - We investigated the polarization characteristics of a mode-locked fiber laser
      gyroscope (MLPLG) formed with a Nd-doped fiber as an optical gain medium and a
      Sagnac loop mirror. The output pulse patterns and the polarization states were
      found to be determined by fiber birefringence in the different sections of the
      MLPLG. We describe the conditions for the MLPLG to operate with automatic
      reciprocity leading to the possibility of phase-error-free operation.

PMID- 21085352
TI  - Freezing-point-blackbody radiation sources for the 29.78-1084.62  degrees C
      temperature range.
AB  - Freezing points of In, Sn, Zn, Al, Ag, Au, and Cu, along with the melting point
      of Ga, are among the defining fixed points of the International Temperature Scale
      of 1990. Accordingly blackbody sources have been commercially produced that
      utilize the freezing/melting points of the above metals for precision radiometric
      calibrations of noncontact thermometers. The cavity emissivity is estimated to be
      0.999, and the fixed point metals have a nominal purity of 99.9999%. We analyze
      the freezing plateau of a Au freezing point blackbody and show that the accuracy
      of calibrating a narrow-band radiometer at 960 nm is (-0.17 +/- 0.02) K.

PMID- 21085353
TI  - Surface temperature correction for active infrared reflectance measurements of
      natural materials.
AB  - Land surface temperature algorithms for the moderate resolution imaging
      spectroradiometer satellite instrument will require the spectral bidirectional
      reflectance distribution function (BRDF) of natural surfaces in the thermal
      infrared. We designed the spectral infrared bidirectional reflectance and
      emissivity instrument to provide such measurements by the use of a Fourier
      transform infrared spectrometer. A problem we encountered is the unavoidable
      surface heating caused by the source irradiance. For our system, the effects of
      the heating can cause a 30% error in the measured BRDF The error caused by
      heating is corrected by temporally curve fitting the radiance signal. This curve
      fitting technique isolates the radiance caused by reflected irradiance. With this
      correction, other factors dominate the BRDF error. It is now ~5% and can be
      improved further. The method is illustrated with measurements of soil BRDF.

PMID- 21085354
TI  - Visible broadband, wide-angle,thin-film multilayer polarizing beam splitter.
AB  - A method is described for the design of a thin-film all-dielectric polarizing
      beam splitter in which the transmittances for p- and s-polarized light are
      greater than 0.96 and less than 0.03, respectively, throughout the spectral
      region extending from 0.40 to 0.70 um, and for an angular field of 12 degrees 
      measured in air.

PMID- 21085355
TI  - Multilayer dielectric structure for enhancement of evanescent waves.
AB  - We describe a type of multilayer dielectric coating designed to enhance the
      intensity of evanescent waves. The coating consists of a stack of alternating
      high- and low-index quarter-wave layers followed by a final low-index layer whose
      thickness is chosen to optimize the evanescent-wave intensity. Indirect
      measurements of the film properties are in good agreement with theory.

PMID- 21085356
TI  - Differential interference contrast microscope with differential detection for
      optimizing image contrast.
AB  - A laser scanning differential interference contrast microscope using a
      differential detection method is proposed. This microscope permits observers to
      control the differential image contrast with a simple operation. Utilizing this
      function, the observers are capable of obtaining the optimized differential image
      whose contrast is most favorable for observation. A simple theoretical analysis
      and experimental considerations are described.

PMID- 21085357
TI  - Applications of the normal-incidence rotating-sample ellipsometer to high- and
      low-spatial-frequency gratings.
AB  - The normal-incidence rotating-sample ellipsometer is an instrument that can be
      used to characterize grating surfaces from the measured ratio rhoof complex
      reflection coefficients r(y)/r(x) of light polarized perpendicular and parallel
      to the grating groove direction. Experimental results at different wavelengths
      for different gratings with spatial frequencies from 150 to 5880 grooves/mm are
      presented. The groove depth of the 5880-grooves/mm gold-coated grating can be
      estimated from the measured rho and rigorous grating theory.

PMID- 21085358
TI  - Angle measurement based on the internal-reflection effect using elongated
      critical-angle prisms.
AB  - Elongated critical-angle prisms that provide multiple reflections have been used
      to increase measurement sensitivity while retaining excellent linearity in the
      recently developed angle-measurement method, angle measurement based on the
      internal-reflection effect.

PMID- 21085359
TI  - Nonimaging secondary concentrators for large rim angle parabolic troughs with
      tubular absorbers.
AB  - For parabolic trough solar collectors with tubular absorbers, we design new
      tailored secondary concentrators. The design is applicable for any rim angle of a
      parabolic reflector. With the secondary, the concentration can be increased by a
      factor of more than 2 with a compact secondary reflector consisting of a single
      piece, even for the important case of a rim angle of 90 deg. The parabolic
      reflector can be used without changes; the reduced absorber is still tubular but
      smaller than the original absorber and slightly displaced toward the primary.

PMID- 21085360
TI  - High-performance wobbling subreflector for the Millimetre and Infrared Testa
      Grigia Observatory 2.6-m telescope.
AB  - The Millimetre and Infrared Testa Grigia Observatory 2.6-m Cassegrain telescope
      has been designed to allow high-sensitivity observations in the millimeter
      spectral range. For this purpose, in order to reduce unwanted contributions from
      local foregrounds, we adopted a sky-chopping technique, by wobbling the telescope
      subreflector. We describe the design and performance of the wobbling system,
      which can endure external forced two and three fields square-wave modulation and
      includes features such as high frequency, high amplitude, high duty cycle, low
      microphonics, and high stability.

PMID- 21085361
TI  - Precise measurement of the refractive index and optical rotatory power of a
      suspension by a delayed optical heterodyne technique.
AB  - By using an optical heterodyne technique, we have demonstrated the detection of
      ballistic photons traveling through a suspension. We measured the propagation
      time of light in a sample with a variable optical delay line in the reference arm
      of an interferometer, using a superluminescent diode as a light source. The
      resolution and accuracy in propagation time measurement were 400 and 3 fs,
      respectively. The minimum detectable rotation angle of 1/10,000 deg was achieved
      with an integration time of 5 s. This system can measure the refractive index and
      optical rotatory power of the suspension in a solvent without disturbing heavy
      scattering from particles in the suspension, because ballistic photons are
      detected.

PMID- 21085362
TI  - Rainbow phenomena applied to the measurement of droplet size and velocity and to
      the detection of nonsphericity.
AB  - An experimental method is presented that detects whether a droplet is spherical.
      The method is based on a comparison between two droplet diameters deduced from
      two different optical interference patterns observed in a rainbow that is created
      by a droplet scattering laser light. Experimental validation has been carried out
      with a CCD camera. Once a rainbow pattern has been identified as coming from a
      spherical droplet, we can derive a reliable droplet velocity and diameter from
      the same interference patterns, using theories for the rainbow that are valid
      only for spherical droplets. Preliminary experiments have been carried out with a
      laser beam and a photomultiplier.

PMID- 21085363
TI  - Time-and-spatial-multiplexing tree topology for fiber-optic Bragg-grating sensors
      with interferometric wavelength-shift detection.
AB  - A combined time-and-spatial-division-multiplexed tree topology with eight fiber
      optic Bragg-grating sensors operating at the 830-nm wavelength was constructed
      and tested for both quasistatic and periodic strain and temperature measurements.
      The system uses a interferometric wavelength-shift discriminator and incorporates
      a reference channel for thermal drift compensation in the output. Dynamic sensor
      sensitivity, as determined by primary noise sources, is evaluated, and numerical
      results are presented and compared with experimental results.

PMID- 21085364
TI  - Theory of fiber-optic, evanescent-wave spectroscopy and sensors.
AB  - A general theory for fiber-optic, evanescent-wave spectroscopy and sensors is
      presented for straight, uncladded, step-index, multimode fibers. A three
      dimensional model is formulated within the framework of geometric optics. The
      model includes various launching conditions, input and output end-face Fresnel
      transmission losses, multiple Fresnel reflections, bulk absorption, and
      evanescent-wave absorption. An evanescent-wave sensor response is analyzed as a
      function of externally controlled parameters such as coupling angle, f number,
      fiber length, and diameter. Conclusions are drawn for several experimental
      apparatuses.

PMID- 21085365
TI  - Edge contribution to forward scattering by spheres.
AB  - Edge functions T1 and T2, which describe the polarization-dependent edge
      contribution to forward scattering by spheres, are derived from the exact Mie
      solution. All the relative refractive indices and the 64 < x < 2048 size
      parameter range are considered. The edge functions significantly improve the
      approximation methods that can be used to calculate forward-scattering patterns.
      For m close to 1, an asymptotic approximation is used. Otherwise, the familiar
      geometrical optics approximation and the similar physical optics approximation
      for glory rays are used. Both geometrical and physical optics equations can be
      deduced from the above-mentioned asymptotic approximation.

PMID- 21085366
TI  - Scattering by random particles on optical surfaces.
AB  - An analytical technique has been developed for calculating the angle-resolved
      light scattering by contaminant particles on smooth opaque surfaces. The
      analytical method was tested by a comparison of measured and calculated
      bidirectional reflectance distribution function (BRDF) values for contaminated
      surfaces. BRDF values were calculated from particle sizes, shapes, and areal
      densities obtained from scanning electron microscope images of the contaminated
      surfaces by a Princeton gamma-tech image analyzer. Measured and calculated BRDF
      values agreed to within the uncertainty associated with the particle
      characterization process for most scattering angles.

PMID- 21085367
TI  - Spatially resolved absolute diffuse reflectance measurements for noninvasive
      determination of the optical scattering and absorption coefficients of biological
      tissue.
AB  - The absorption and transport scattering coefficients of biological tissues
      determine the radial dependence of the diffuse reflectance that is due to a point
      source. A system is described for making remote measurements of spatially
      resolved absolute diffuse reflectance and hence noninvasive, noncontact estimates
      of the tissue optical properties. The system incorporated a laser source and a
      CCD camera. Deflection of the incident beam into the camera allowed
      characterization of the source for absolute reflectance measurements. It is shown
      that an often used solution of the diffusion equation cannot be applied for these
      measurements. Instead, a neural network, trained on the results of Monte Carlo
      simulations, was used to estimate the absorption and scattering coefficients from
      the reflectance data. Tests on tissue-simulating phantoms with transport
      scattering coefficients between 0.5 and 2.0 mm(-1) and absorption coefficients
      between 0.002 and 0.1 mm(-1) showed the rms errors of this technique to be 2.6%
      for the transport scattering coefficient and 14% for the absorption coefficients.
      The optical properties of bovine muscle, adipose, and liver tissue, as well as
      chicken muscle (breast), were also measured ex vivo at 633 and 751 nm. For muscle
      tissue it was found that the Monte Carlo simulation did not agree with
      experimental measurements of reflectance at distances less than 2 mm from the
      incident beam.

PMID- 21085368
TI  - Imaging of highly turbid media by the absorption method.
AB  - The results of a study on imaging that is based on the absorption method are
      presented. This method is based on attenuation measurements carried out in the
      presence of a sufficiently high absorption coefficient by the use of a continuous
      wave source. The benefit of absorption on image quality comes from the strong
      attenuation of photons traveling along long trajectories. When the absorption
      coefficient is increased, the received energy decreases, but the mean path length
      of received photons decreases. The effect of increasing the absorption
      coefficient is similar to that of decreasing the gating time when the time-gating
      technique is used. Experimental results showed that the spatial resolution
      obtained with the absorption technique is similar to that obtained with the time
      gating technique.

PMID- 21085369
TI  - Fluorescence-lifetime determination in tissues or other scattering media from
      measurement of excitation and emission kinetics.
AB  - Measurements of nanosecond and subnanosecond fluorescence lifetimes are
      restricted to dilute, nonscattering systems since excitation and emission photon
      times of flight significantly affect measured fluorescent decay kinetics. We
      provide the theoretical rationale for frequency-domain measurements of phase
      shift and amplitude demodulation made at excitation and emission wavelengths for
      direct determination of lifetimes in tissues and other scattering media. We
      confirm our analytical expressions using standard laser dyes such as 3,3'
      diethylthiatricarbocyanine iodide, IR- 125, and IR- 140 in polystyrene
      suspensions with similar scattering properties as tissues. Our results have
      significant implication for lifetime-based spectroscopy in tissues and other
      scattering media.

PMID- 21085370
TI  - Optical memory: introduction by the feature editors.

PMID- 21085371
TI  - Coupling kinetics of the photorefractive hologram.

PMID- 21085372
TI  - A precision tester for studies of holographic optical storage materials and
      recording physics.
AB  - The design and the realization of an advanced precision optical test stand for
      evaluating materials and developing tools and techniques for holographic digital
      data storage are described. This apparatus allows studies of holographic
      recording materials and recording physics to be performed in the context of
      practical data storage. The system concept, its implementation, and its
      performance are described, and examples of holographic storage in photorefractive
      materials are discussed.

PMID- 21085373
TI  - Compact holographic storage demonstrator with rapid access.
AB  - We discuss the design of a complete, compact holographic storage demonstrator
      based on a combination of spatial and angular multiplexing and using acousto
      optic deflectors for rapid nonmechanical access. We also describe the
      implementation of this design and preliminary results of both the analog storage
      and the retrieval of 20,000 holograms in twenty 1-mm-thick layers of a lithium
      niobate crystal and of the digital storage and error-free retrieval of color
      images by using error-correcting techniques.

PMID- 21085374
TI  - Sparse-wavelength angle-multiplexed volume holographic memory system: analysis
      and advances.
AB  - We present and analyze our hybrid wavelength-and-angle-multiplexed volume
      holographic memory system. The hybridization of wavelength and angle multiplexing
      relaxes demands on spectral-tuning sources, angle-tuning devices, and optical
      system numerical apertures while maintaining a large K-space addressability. We
      consider realistic properties of our volume holographic memory system, addressing
      practical issues such as storage density and material-dependent photon-limited
      information throughput. Finally, we present experimental results of the storage
      of 2000 sparse-wavelength angle-multiplexed volume holograms in a 1.86-cm3 volume
      of lithium niobate.

PMID- 21085375
TI  - High-density recording in photopolymer-based holographic three-dimensional disks.
AB  - The performance specifications of a holographic three-dimensional disk system are
      experimentally characterized. A surface density of 10 bits/um(2) is
      experimentally demonstrated with a 100-um-thick photopolymer as the recording
      medium.

PMID- 21085376
TI  - High-speed, acousto-optically addressed optical memory.
AB  - A page-oriented, angle-multiplexed volume holographic optical-memory recording
      system has been constructed. This memory is addressed by the use of an acousto
      optic deflector with a random-access time of 16 us per page. This enables data
      transfer rates of 5.28 Gbits/s when pages of binary data are being stored. The
      reconstruction quality of images stored as memory pages is assessed with the
      quality achieved with the acousto-optic device compared with that achieved with
      the original recording optics.

PMID- 21085377
TI  - Shift multiplexing with spherical reference waves.
AB  - Shift multiplexing is a holographic storage method particularly suitable for the
      implementation of holographic disks. We characterize the performance of shift
      multiplexed memories by using a spherical wave as the reference beam. We derive
      the shift selectivity, the cross talk, the exposure schedule, and the storage
      density of the method. We give experimental results to verify the theoretical
      predictions.

PMID- 21085378
TI  - Optical design for page access to volume optical media.
AB  - 4F lens designs are optimized for parallel access to volume holographic memories.
      Aberrations, diffraction, and component tolerancing are considered for their
      impact on parallelism, crystal information density, and overall system storage
      density. We find that a parallelism of >= 10(5) bits per page and a crystal
      information density of ~2 Mbits/mm(3) are achievable with standard optical
      elements and that advanced designs offer significant improvements. Crystal
      surface tolerance measurements show that a diffraction-limited performance is
      achievable over apertures of 7.1 mm for LiNbO(3) and 1.5 mm for KNSBN(60). Lens
      tolerancing simulations show that lens decenter degrades peak parallelism and
      peak crystal information density. Anew nonconfocal 4F system design with improved
      performance is presented.

PMID- 21085379
TI  - Signal detection for page-accessoptical memories with intersymbol interference.
AB  - We propose a technique for data detection in a two-dimensional page-access
      optical memory. The technique combines sequence detection by the use of the
      Viterbi algorithm with decision feedback to improve the bit-error-rate
      performance in a system corrupted by intersymbol interference. It has an
      advantage in that it can be operated on a row-by-row basis as data are output
      from the optical detector. Use of the proposed scheme might ease the design
      tolerances of the optical components or permit the use of large data pages.

PMID- 21085380
TI  - Photonic page buffer based on GaAs multiple-quantum-well modulators bonded
      directly over active silicon complementary-metal-oxide-semiconductor (CMOS)
      circuits.
AB  - We present a 2-kbit, 50-Mpage/s, photonic first-in, first-out page buffer based
      on gallium arsenide/aluminium-gallium arsenide multiple-quantum-well diodes that
      are flip-chip bonded to submicrometer silicon complementary-metal-oxide
      semiconductor circuits. This photonic chip provides nonvolatile storage
      (buffering), asynchronous-to-synchronous conversion, bandwidth smoothing,
      tolerance to jitter or skew, spatial format conversion, wavelength conversion,
      and independent flow control for the input and the output channels. It serves as
      an interface chip for parallel-accessed optical bit-plane data. It represents the
      first smart-pixel array that accomplishes the vertical integration of multiple
      quantum-well modulators and detectors directly over active silicon VLSI circuits
      and provides over 340 transistors per optical input-output. Results from high
      speed single-channel testing and real-time array operation of the photonic page
      buffer are reported.

PMID- 21085381
TI  - Optoelectronic-cache memory system architecture.
AB  - We present an investigation of the architecture of an optoelectronic cache that
      can integrate terabit optical memories with the electronic caches associated with
      high-performance uniprocessors and multiprocessors. The use of optoelectronic
      cache memories enables these terabit technologies to provide transparently low
      latency secondary memory with frame sizes comparable with disk pages but with
      latencies that approach those of electronic secondary-cache memories. This
      enables the implementation of terabit memories with effective access times
      comparable with the cycle times of current microprocessors. The cache design is
      based on the use of a smart-pixel array and combines parallel free-space optical
      input-output to-and-from optical memory with conventional electronic
      communication to the processor caches. This cache and the optical memory system
      to which it will interface provide a large random-access memory space that has a
      lower overall latency than that of magnetic disks and disk arrays. In addition,
      as a consequence of the high-bandwidth parallel input-output capabilities of
      optical memories, fault service times for the optoelectronic cache are
      substantially less than those currently achievable with any rotational media.

PMID- 21085382
TI  - Three-dimensional optical bit-memory recording and reading with a photorefractive
      crystal: analysis and experiment.
AB  - We analyze the three-dimensional refractive-index distribution that is induced
      locally when a laser beam is focused onto a very small region in a
      photorefractive crystal. The formation of the index distribution is deduced from
      the temporal behavior of the electron density distribution in the crystal under
      non-steady-state conditions. The density distribution is computed by the use of a
      set of the recurrence relations that was derived from Kukhtarev's equations,
      which describe the transport of electrons in time. In particular, we calculated
      the index distribution formed in Fe-doped LiNbO(3) crystals. To verify the
      validity of our analysis, we read, by using a phase-contrast microscope,
      refractive-index dots that were recorded in Fe-doped LiNbO(3) crystals. A good
      agreement was obtained between experimental results and the calculated phase
      contrast images when the characteristics of the imaging system are taken into
      account. We also found that the induced index change is largest when the c axis
      of the LiNbO(3) crystal is oriented parallel to the polarization direction of the
      reading beam. Under this optimal condition, we succeeded in recording up to 10
      layers of readable data in a LiNbO(3) crystal.

PMID- 21085383
TI  - Differential phase-contrast microscope with a split detector for the readout
      system of a multilayered optical memory.
AB  - A transmission differential phase-contrast microscope with a split detector is
      used as a readout system for a multilayered three-dimensional optical memory. The
      system is applicable to data recorded as refractive-index changes. The system is
      compact and easy to use. The three-dimensional optical transfer function for the
      system is derived. This shows that the spatial bandwidth of the system is the
      same as that of a conventional microscope with incoherent illumination but with
      much improved contrast. Six layers of information are recorded in a photopolymer
      and are read out with little cross talk and high contrast.

PMID- 21085384
TI  - Optical data storage readout with quadrant pupil detection.
AB  - A novel detection scheme that uses combinations of quadrant signals derived in a
      pupil of the optical system is described for optical storage devices. The signals
      arise because of an asymmetry in the reflected light distribution when the
      focused spot scans data with a nonzero tracking offset. Theoretical and scalar
      diffraction characterization indicates that the signals may be useful for
      improved data density by reducing intertrack interference (cross talk). The
      signals may also be useful for providing a tracking error signal.

PMID- 21085385
TI  - Two-dimensional finite-difference time-domain simulation for rewritable optical
      disk surface structure design.
AB  - A novel two-dimensional finite-difference time-domain simulation for treating the
      interaction of a focused beam with a rewritable optical disk is detailed and
      experimentally validated. In this simulation, the real material properties of the
      rewritable multilayer stack and the aperiodic nature of the disk topography are
      considered. Excellent agreement is obtained between calculated and measured push
      pull tracking servosignals for magneto-optical disks with pregrooves and infinite
      length preformat pits. To demonstrate the utility of the simulation as a design
      tool, the design process for a 0.9-um track pitch, continuous, composite
      servoformat magneto-optical disk is given.

PMID- 21085386
TI  - Pseudorandom phase-only encoding of real-time spatial light modulators.
AB  - We previously proposed a method of mapping full-complex spatial modulations into
      phase-only modulations. The Fourier transform of the encoded modulations
      approximates that of the original complex modulations. The amplitude of each
      pixel is encoded by the property that the amplitude of a random-phasor sum is
      reduced corresponding to its standard deviation. Pseudorandom encoding is
      designed for phase-only spatial light modulators that produce 360 degrees  phase
      shifts. Because such devices are rare, experiments are performed with a 326
      degrees modulator composed of two In Focus model TVT6000 liquid-crystal displays.
      Qualitative agreement with theory is achieved despite several nonideal properties
      of the modulator.

PMID- 21085387
TI  - Coherence confocal-imaging system for enhanced depth discrimination in
      transmitted light.
AB  - A system for image-plane holography that uses a spectrally and spatially broad
      radiation source is analyzed and shown to provide depth discrimination in excess
      of that offered by conventional confocal imaging. The enhanced depth
      discrimination is a consequence of two factors: the simultaneous reduction of
      both the spatial and the temporal coherence of the source, and the special
      property of certain grating interferometers of presenting a spectrally dispersed
      light beam to the object while forming achromatic fringes at the hologram
      recording plane.

PMID- 21085388
TI  - Optimum rotation-invariant filter for disjoint-noise scenes.
AB  - We introduce an optimum matched filter for rotation-invariant pattern recognition
      in scenes with disjoint noise. The optimum filter maximizes the ratio between the
      correlation-peak intensity and the correlation-output energy; in order to ensure
      rotation invariance, we assume the filter to take the form of a circular-harmonic
      function. The performance of this new filter is tested by computer simulations
      with a variety of natural and artificial backgrounds. The results obtained from
      these tests show an excellent performance much better than the classical circular
      harmonic function (the filter that maximizes the signal-to-noise ratio while
      maintaining rotation invariance).

PMID- 21085389
TI  - Fiber Raman background study and its application in setting up optical fiber
      Raman probes.
AB  - Fiber Raman background spectra of different types of fused-silica fibers are
      studied and compared. The results show the following: (a) all the background
      spectra are very similar and comparable with Raman spectra of fused silica,
      regardless of the difference in the cladding and buffer materials; (b) the
      overall background intensity increases with the fiber numerical aperture but has
      no obvious relation with the core diameter. Both experimental evidence and
      theoretical explanation have been provided for these views. A simple and
      unfiltered fiber probe for surface-enhanced Raman scattering detection with low
      fiber Raman background interference is constructed, and the optimum configuration
      of the probe is suggested and discussed based on the results of the background
      study.

PMID- 21085390
TI  - Design of a low-loss off-axis beam expander.
AB  - A method is given for the build up of simple off-axis beam expanders for Gaussian
      beams with low aberrations. In particular we show that it is possible to correct
      exactly the astigmatism in such a system. A realistic example is given.

PMID- 21085391
TI  - Iterative inversion of phase-Doppler-anemometry size distributions from sprays of
      optically inhomogeneous liquids.
AB  - Using phase Doppler anemometry (PDA) to investigate sprays of optically
      inhomogeneous liquids leads to blurred measured size distributions. The blurring
      function is formed by performance of PDA measurements on single-size droplets
      generated by a piezoelectric droplet generator. To obtain the undistorted droplet
      size distributions, a constrained iterative inversion algorithm is applied. The
      number of iteration steps to achieve the best possible restoration is determined
      by the use of synthetically generated data that has noise properties similar to
      the measured histograms. The obtained size distributions are checked by
      comparison with undistorted measurement results of an atomized optical
      homogeneous liquid.

PMID- 21085392
TI  - Real-time measurement of transverse-mode-mixing effects in a Q-switched Nd:YAG
      laser.
AB  - We describe a novel apparatus for the real-time characterization of transverse
      mode-mixing effects by monitoring the fluctuations of the M(2) factor defined by
      Siegman [Proc. Soc. Photo-Opt. Instrum. Eng. 1224, 2 (1990)]. A comparison
      between the results provided by our approach and those obtained by the use of a
      standard measurement apparatus has shown a satisfactory agreement within the
      experimental uncertainty.

PMID- 21085393
TI  - Highly efficient wideband continuum generation in a single-mode optical fiber by
      powerful broadband laser pumping.
AB  - By pumping a single-mode optical fiber with a powerful broadband nonselective dye
      laser, we obtain a high-efficiency wideband continuum (530-930 nm) with nonlinear
      conversion efficiency exceeding 90%. Experimental conditions for a coherent
      regime of broadband stimulated Raman scattering are created, which in combination
      with the broadband self-phase modulation and the four-photon parametric processes
      leads to a spectral broadening and to the continuum formation. The influence of
      the pump laser spectral linewidth on the nonlinear conversion efficiency is
      analyzed and investigated by comparative experiments at narrow-band and broadband
      laser excitations.

PMID- 21085394
TI  - Cw industrial rod YAG:Nd(3+) laser with an intracavity active bimorph mirror.
AB  - A special type of resonator with an intracavity wide-aperture active mirror was
      built, and a concave spherical bimorph active corrector was investigated. An
      increase of laser beam quality by a factor of 2-2.5 was achieved in a multimode
      regime of laser generation with an intracavity-controlled mirror. It was shown
      that various radiation mode structures could be formed at the laser output and in
      the far-field zone.

PMID- 21085396
TI  - Efficient and stable operation of a high-brightness cw 500-W Nd:YAG rod laser.
AB  - Enhanced efficiency and stabilized beam-power generation were proved for a high
      brightness cw-based 500-W Nd:YAG rod laser by compensation of the thermally
      induced bifocusing of the Nd:YAG rod. Maximum laser power of 500 W cw was
      obtained at lamp input power of 18.4 kW, with beam quality M(2) = 19 oromegatheta
      (radius x, the half-angle of divergence) = 6.4 mm mrad and power fluctuation of
      less than 1%.

PMID- 21085395
TI  - Encapsulated rod for efficient thermal management in diode-side-pumped Nd:YAG
      lasers.
AB  - Theoretical calculations of energy deposition, temperature, and thermally induced
      birefringence are presented for a diode-side-pumped Nd:YAG laser that has the
      laser rod optically fixed into a right-rectangular prism with a square cross
      section. The design provides uniform cooling of the rod and allows for a number
      of conduction-cooling techniques to be used. Average output powers >5 W are
      feasible at optical-to-optical efficiencies of ~20% for long-pulse operation and
      ~10% for Q-switched operation for quite simple and convenient cooling
      arrangements (e.g., Peltier cooling).

PMID- 21085397
TI  - Synchronization of pulsed Tksapphire lasers and its application to difference
      frequency mixing for tunable infrared generation.
AB  - A simple and effective technique for synchronizing two independent Ti: sapphire
      lasers was developed and used for difference-frequency generation. By control of
      pump intensity, buildup times of these lasers were adjusted to coincide for any
      combination of wavelengths that was needed for the production of a desired
      difference frequency. Synchronized pulses were mixed at a AgGaS(2) crystal,
      producing infrared pulses from 6.2 to 9.7 um. Characteristic features of the
      method as well as its possible extension of the tuning range are discussed.

PMID- 21085398
TI  - Ho:CaF(2) solid-state saturable-absorber Q switch for the 2-um
      Tm,Cr:Y(3)Al(5)O(12) laser.
AB  - The holmium-doped calcium fluoride (Ho:CaF(2)) crystal was shown to be an
      effective solid-state saturable-absorber Q-switch for a flash-lamp-pumped
      Tm,Cr:Y(3)Al(5)O(12) laser at 2.017 um. With a 1-cm-thick Ho(0.5%),Er(5%):CaP(2)
      saturable absorber and a 6.3% output coupler, a single Q-switched laser pulse of
      51 mJ in energy and 60 ns in duration was obtained at a flash-lamp input energy
      of 85 J. With a 14.6% output coupler, a typical Q-switched laser pulse of 84 mJ
      and 82 ns was observed.

PMID- 21085399
TI  - Megahertz-repetition-rate Nd:glass fiber laser.
AB  - Stable trains of 100-200-ns-long pulses are obtained at 0.46-1.06-MHz repetition
      rates in a Nd:glass fiber laser by driving large-amplitude relaxation
      oscillations at or below their resonance. Numerical simulations agree
      qualitatively with temporal profiles of the output power. We show that the
      maximum pulse-repetition rate of a relaxation-oscillation laser increases as the
      square root of pump power at low P and that its theoretical upper limit is close
      to the pulse rate of a mode-locked laser.

PMID- 21085400
TI  - Visible single-shot autocorrelator in BaF(2) for subpicosecond KrF laser pulses.
AB  - A single-shot autocorrelator based on the two-photon excited fluorescence of
      BaF(2) in the visible region at 400 nm has been developed for ultrashort KrF
      laser pulses at 248 nm. Operation in the visible region offers simplification in
      the required optical components as compared with previously reported systems,
      which used ultraviolet fluorescence emission. The fluorescence intensity is also
      used to measure the two-photon absorption coefficient of BaF(2), yielding a value
      of beta = 1.3 +/- 0.4 * 10(-10) cm/W.

PMID- 21085401
TI  - Electro-optic modulation in an anisotropic artificial Kerr medium.
AB  - We describe the performance of intensity and phase modulators that use an aqueous
      suspension of polytetrafluoroethylene (PTFE) microparticles. In this medium, the
      electro-optic effect is caused by the reorientation of anisotropic microparticles
      in an applied electric field. The intensity modulator was constructed in the Kerr
      geometry by the use of a sample path length of 20 um. The response time of the
      modulator is less than 25 ms, and the depth of modulation was measured to be 28
      dB for a switching voltage of 134 V(rms). The switching voltage necessary to
      achieve a pi-phase shift with the phase modulator is less than 30 (Vrms).

PMID- 21085402
TI  - Fiber-optic polarizer using birefringent crystal as a cladding.
AB  - A new type of fiber-optic polarizer has been developed in which the birefringent
      material is formed around the core fiber as a cladding. A NaNO(3) single crystal
      is used as the birefringent material. The extinction ratios for the polarized
      light are measured for fibers with cores of various radii and claddings of
      various lengths. The extinction ratios obtained are typically 31.2 dB for a core
      diameter of 6 um and a cladding length of 6 mm.

PMID- 21085403
TI  - Split-spectrum intensity-based optical fiber sensors for measurement of
      microdisplacement, strain, and pressure.
AB  - A self-referencing technique compensating for fiber losses and source
      fluctuations in reflective air-gap intensity-based optical fiber sensors is
      described. A dielectric multilayer short-wave-pass filter is fabricated onto or
      attached to the output end face of the lead-in-lead-out multimode fiber. The
      incoming broadband light from a white light or a light-emitting diode is
      partially reflected at the filter. The transmitted light through the filter
      projects onto a mirror. The light returning from the reflecting mirror is
      recoupled into the lead-in-lead-out fiber. These two reflections from the filter
      and the reflecting mirror are spectrally separated at the detector end. The power
      ratio of these two reflections is insensitive to source fluctuations and fiber
      bending loss. However, because the second optical signal depends on the air-gap
      separation between the end face of the lead-in-lead-out fiber and the reflecting
      mirror, the ratio provides the information on the air-gap length. A resolution of
      0.13 um has been obtained over a microdisplacement measurement range of 0-254 um.
      The sensor is shown to be insensitive to both fiber-bending losses and variations
      in source power. Based on this approach, a fiber-strain sensor was fabricated
      with a multilayer interference filter directly fabricated on the end face of the
      fiber. A resolution of 13.4 microstrain was obtained over a measurement range of
      0-20,000 microstrain with a gauge length of 10 mm. The split-spectrum method is
      also incorporated into a diaphragm displacement-based pressure sensor with a
      demonstrated resolution of 450 Pa over a measurement range of 0-0.8 MPa.

PMID- 21085404
TI  - Accurate method for determining the refractive-index profiles of planar
      waveguides in uniaxial media with the optical axis normal to the surface.
AB  - A new method for characterization of uniaxial planar waveguides from their
      measured effective mode indices is presented. The theory is outlined and
      expressions for efficient computer analysis are given. Uniaxial waveguide samples
      have been made in c-cut LiNbO(3) by proton exchange with and without post
      annealing in order to test the method on both steplike and graded-index profiles.
      The resulting characterization of the samples is discussed in relation to the
      inverse WKB method. Finally, the importance of incorporating the effects of
      material birefringence in the characterization of these kinds of waveguides is
      investigated.

PMID- 21085405
TI  - Experimental study of the geometric group-delay dispersion in graded-index media.
AB  - We use the highly sensitive method of spatially coherent white-light
      interferometry to measure the geometric group-delay dispersion in graded-index
      media. Our measurements confirm previous analyses that the geometric dispersion
      produced by off-axis beam propagation is anomalous (negative), hence may be used
      to eliminate the ubiquitous positive dispersion in optical systems. Fabrication
      of large index-gradient waveguides optimal for dispersion compensation is
      discussed.

PMID- 21085406
TI  - Simultaneous machining of parallel grooves in SnO(2) thin films using a Nd:YAG
      laser and a kinoform.
AB  - A kinoform is used to split the beam of a Nd:YAG laser into six beams. The laser
      beams are, by means of optical fibers and collimating-focusing optics,
      transferred to the surface to be machined. Thus multiple grooves can be machined
      simultaneously. For demonstration, 100-um-wide grooves are simultaneously
      machined into a SnO(2) thin film deposited on a glass substrate. The resulting
      grooves are well isolated. This result shows that the technique could be used,
      for example, in solar cell manufacturing to increase the efficiency of laser
      scribing.

PMID- 21085407
TI  - High-pulse-repetition-freqyency lidar system using a single telescope for
      transmission and reception.
AB  - The design, construction, and operation of a stratospheric Rayleigh lidar system
      is outlined. The lidar system was designed to operate as a Doppler lidar;
      however, for the first stage of the project it was set up to operate in a manner
      similar to a more conventional stratospheric Rayleigh lidar. This system includes
      a number of unique design features, including a high-pulse-repetition-frequency
      laser and the use of a single 1-m-diameter telescope for transmission of the
      laser pulse and reception of the backscattered light. An associated high-speed
      rotating shutter system switches the optical system from the transmission to the
      reception mode. The system was operated at Adelaide, Australia (35 degrees  S,
      138 degrees  E). Scattering ratio and temperature profiles are calculated for
      data collected during the period from 10 March 1992 to 11 May 1993. The
      scattering ratio profiles clearly show the reduction in the scattering from the
      stratospheric aerosol layer. This is due to the removal of the aerosol injected
      by the eruption of Mt. Pinatubo. The measured relative density profiles show very
      good agreement with the Cospar international reference atmosphere model
      densities, as do the temperature profiles calculated from these.

PMID- 21085408
TI  - Lidar for remote measurement of ozone in the exhaust plumes of launch vehicles.
AB  - Large quantities of chlorine and alumina particles are injected directly into the
      stratosphere by the current fleet of launch vehicles. Environmental concerns have
      been raised over the impact of the rocket exhaust on the ozone layer. Recently
      differential absorption lidar (DIAL) was selected for remote sensing of ozone
      density within the plumes of Titan IV launch vehicles. The application of DIAL to
      this very challenging problem is described, and an implementation of UV-ozone
      DIAL is discussed that holds promise for this application.

PMID- 21085410
TI  - Derivation of the aerosol size distribution from a bistatic system of a
      muitiwavelength laser with the singular value decomposition method.
AB  - Estimation of aerosol size distributions from measurements of scattered light
      intensity by the use of a bistatic system with a multiwavelength laser is
      presented. We investigated the effects of inversion of the scattered intensity on
      calculated aerosol size distribution in a numerical experiment. Two model aerosol
      size distributions were used, one a Junge type widely known as a typical example
      of the size distribution of suspended particles in the atmosphere and the other a
      log-normal type as an example of the monodisperse distribution. A singular value
      decomposition was applied to the inversion to infer the size distribution from
      the kernel function and the scattered light intensity. In the physical
      experiment, the size distributions were successfully inferred from analysis of
      the scattered light intensity from an artificial polystyrene latex aerosol.

PMID- 21085409
TI  - Multiple scattering from clear atmosphere obscured by transparent crystal clouds
      in satellite-borne lidar sensing.
AB  - The contribution of multiple scattering to a spaceborne lidar return from clear
      molecular atmosphere obscured by transparent upper-level crystal clouds is
      assessed by the use of the variance-reduction Monte Carlo technique. High
      anisotropy of scattering in the forward direction by polydispersions of ice
      crystals is the basis of a significant effect of multiple scattering for small
      values of the lidar receiver field of view. Because of scattering by large
      nonspherical crystal particles, the lidar signal backscattered from the molecular
      atmosphere under the cloud increases significantly compared with the single
      scattering return. The ratio of the multiple-to-single-scattering contributions
      from the clear atmosphere hidden by the clouds is greater than from the crystal
      clouds themselves, and it is proportional to the values of cloud optical
      thickness.

PMID- 21085411
TI  - Correction of phase anomalies of atmospheric emission spectra by the double
      differencing method.
AB  - Atmospheric emission measurements with the cryogenic airborne Michelson
      Interferometer for Passive Atmospheric Sounding revealed strongly disturbed phase
      and magnitude spectra. They were corrected with the double-differencing method:
      The phase information implied in the line structure of atmospheric spectra is
      used to specify a phase shift with respect to an instrumental phase spectrum,
      which was determined once from calibration measurements with the differencing
      method of Revercomb et al. [Appl. Opt. 27, 3210 (1988)].

PMID- 21085412
TI  - Temperature influence on light absorption by fresh water and seawater in the
      visible and near-infrared spectrum.
AB  - The influence of temperature on light transmission in the spectral range from 400
      to 760 nm has been determined in a two-cell instrument constructed especially for
      this purpose. Light transmission was measured over a 1-m path length in both a
      photometric and a spectral mode in double-ion-exchanged fresh water and filtered
      seawater with a salinity of approximately 25%?. For both groups of samples the
      temperature-dependence coefficient of the absorption was found to be -0.00091 +/-
      0.00006 m(-1) K(-1) in the range from 400 to 550 nm, in contrast to earlier
      findings. Reproducible signals could be observed only when the samples were left
      undisturbed for long periods of time between shifts in temperature. The
      temperature was scanned in alternating directions between 6 and 30  degrees C in
      steps of +/- 2  degrees C. The time for recording a set of data was between 2 and
      3 weeks. Finally, the temperature dependences of the absorption spectra were
      recorded in the range 400 to 760 nm. These measurements are only partially in
      agreement with earlier measurements.

PMID- 21085413
TI  - Coherent anti-Stokes Raman scattering measurements of N(2)(X, v) at low pressures
      corrected for stimulated Raman scattering.
AB  - Number density measurements of the populations of the vibrational states of the
      electronic ground state of molecules that use scanning coherent anti-Stokes Raman
      scattering (CARS) spectroscopy at pressures in which Doppler broadening dominates
      can be strongly influenced by population changes caused by the stimulated Raman
      process. Such measurements have been carried out in heterogeneous deactivation
      studies of vibrationally excited N(2) on various solid surfaces at 17 Torr. This
      process perturbs the populations of the states connected by the incident fields.
      It typically reduces the population difference and therefore reduces the observed
      CARS signal. Thus, as the incident laser irradiance increases, the observed
      signal exhibits saturation. A linear relationship for this effect in terms of the
      average laser powers is derived, providing a scheme for calibrating the initial
      onset of this saturation process. This calibration method permits simple
      corrections of the CARS data for saturation.

PMID- 21085414
TI  - Experimental comparison of single-shot broadband vibrational and dual-broadband
      pure rotational coherent anti-Stokes Raman scattering in hot air.
AB  - Broadband vibrational and dual-broadband pure rotational coherent anti-Stokes
      Raman scattering (CARS) have been compared in a high-temperature oven, in which
      the accuracy and single-shot precision of gas temperature and relative O(2)- and
      N(2)-concentration measurements in hot air were probed over a temperature range
      that is typical for many combustion processes. To ensure a realistic comparison,
      we used nearly the same experimental setup for both CARS techniques. Besides
      temperature information, dual-broadband pure rotational CARS offers the
      possibility of achieving simultaneous single-shot concentration measurements. The
      comparison shows that this technique also has significant advantages in
      temperature evaluation over a large temperature range in comparison with
      vibrational CARS.

PMID- 21085415
TI  - Use of sky brightness measurements from ground for remote sensing of particulate
      polydispersions.
AB  - The software code SKYEAD.pack for retrieval of aerosol size distribution and
      optical thickness from data of direct and diffuse solar radiation is described;
      measurements are carried out with sky radiometers in the wavelength range 0.369
      1.048 um. The treatment of the radiative transfer problem concerning the optical
      quantities is mainly based on the IMS (improved multiple and single scattering)
      method, which uses the delta-M approximation for the truncation of the aerosol
      phase function and corrects the solution for the first- and second-order
      scattering. Both linear and nonlinear inversion methods can be used for
      retrieving the size distribution. Improved calibration methods for both direct
      and diffuse radiation, the data-analysis procedure, the results from the proposed
      code, and several connected problems are discussed. The results can be summarized
      as follows: (a) the SKYRAD.pack code can retrieve the columnar aerosol features
      with accuracy and efficiency in several environmental situations, provided the
      input parameters are correctly given; (b) when data of both direct and diffuse
      solar radiation are used, the detectable radius interval for aerosol particles is
      approximately from 0.03 to 10 um; (c) besides the retrieval of the aerosol
      features, the data-analysis procedure also permits the determination of average
      values for three input parameters (real and imaginary aerosol refractive index,
      ground albedo) from the optical data; (d) absolute calibrations for the sky
      radiometer are not needed, and calibrations for direct and diffuse radiation can
      be carried out with field data; (e) the nonlinear inversion gives satisfactory
      results in a larger radius interval, without the unrealistic humps that occur
      with the linear inversion, but the results strongly depend on the first-guess
      spectrum; (f) aerosol features retrieved from simulated data showed a better
      agreement with the given data for the linear inversion than for the nonlinear
      inversion.

PMID- 21085416
TI  - Chirped femtosecond pulse scattering by spherical particles.
AB  - Generalized Lorentz-Mie formulas are used to study the scattering characteristics
      when a chirped femtosecond pulse illuminates a spherical particle. For a linear
      chirped Gaussian pulse with the envelope function g(tau) = exp[-pi(1 +
      ib)tau(2)], dimensionless parameter b is defined as a chirp. The calculation
      illustrated that even for pulses with a constant carrier wavelength (lambda(0) =
      0.5 um) and pulse-filling coefficient (l(0) = 1.98), the efficiencies for
      extinction and scattering differ very much between the carrier wave and the
      different chirped pulses. The slowly varying background of the extinction and the
      scattering curves is damped by the chirp. When the pulse is deeply chirped, the
      maxima and minima of the background curves reduce to the point where they
      disappear, and the efficiency curves illustrate a steplike dependence on the
      sphere size. Another feature is that the chirped-pulse scattering seems blind: it
      depends only on the amount of chirp (|b|), regardless of upchirp (b > 0) or
      downchirp (b< 0).

PMID- 21085417
TI  - Multiple scattering effects on the remote sensing of the speed of sound in the
      ocean by Brillouin scattering.
AB  - Monte Carlo calculations have been performed to investigate the effect of
      multiple scattering on the frequency spectra caused by Brillouin scattering in
      the ocean. It is shown that the use of the frequency spectra to determine the
      speed of sound profile and the hydrosol backscattering probability is stable
      under multiple scattering because the problem is limited to single backscattering
      events.

PMID- 21085418
TI  - Prediction of reverse radiation pressure by generalized Lorenz-Mie theory.
AB  - Radiation pressure exerted on a spherical particle by one extremely focused
      Gaussian beam is investigated by the use of generalized Lorenz-Mie theory (GLMT).
      Particular attention is devoted to reverse radiation pressure. GLMT predictions
      for different descriptions of the incident beam are compared with
      electrostriction predictions when the particle size is smaller than the
      wavelength and with geometric-optics predictions when the particle size is larger
      than the wavelength.

PMID- 21085419
TI  - Patents.
AB  - 5,414,555; 5,430,634; 5,436,452; 5,438,187; 5,438,198; 5,438,412; 5,442,172;
      5,446,581; 5,446,588; 5,450,196; 5,452,125; 5,456,260; 5,459,308;

PMID- 21085420
TI  - Fourier-transform spectroscopy: new methods and applications: introduction by the
      feature editors.
AB  - We are pleased to introduce this special issue of papers on Fourier-transform
      spectroscopy, which grew out of a recent topical meeting sponsored by the Optical
      Society of America. The topical meeting welcomed all researchers who practice the
      art of Fourier-transform spectroscopy in the laboratory, in the atmosphere, and
      in space. The power and the wide applicability of Fourier-transform spectroscopy
      unite these fields with a common mathematical and instrumental bond. The meeting
      probed each of these areas in depth, bringing out new ideas for instrumentation,
      analysis, and applications. There was a strong sentiment at the meeting that the
      quality of papers and posters was exceptionally high and that it would be
      important for future progress in the field to have the results of this meeting
      captured in print. This special issue is the fruit of that effort.

PMID- 21085421
TI  - Seismology with a Fourier-transform spectrometer: applications to giant planets
      and stars.
AB  - A method to detect the acoustic oscillation spectrum of giant planets and stars
      exploits the multiplex properties of a Fourier-transform spectrometer (FTS). It
      is based on measurement of the small Doppler shift related to the oscillation of
      the atmosphere measured from all the lines in a portion of the planetary or the
      stellar spectrum directly from the interferogram. The resulting amplitude
      modulation of the output signal is recorded continuously over several consecutive
      nights at a fixed path difference selected from criteria of optimum efficiency.
      Hence the Fourier transform of this signal yields the pressure-mode spectrum of
      the object. Applications to Jupiter, Saturn, and Procyon, observed in this mode
      with the step-scan FTS installed in the Canada-France-Hawaii Telescope, are
      presented. Future projects are discussed.

PMID- 21085422
TI  - Observations of the infrared solar spectrum from space by the ATMOS experiment.
AB  - The final flight of the Atmospheric Trace Molecule Spectroscopy experiment as
      part of the Atmospheric Laboratory for Applications and Science (ATLAS-3) Space
      Shuttle mission in 1994 provided a new opportunity to measure broadband (625-4800
      cm(-1), 2.1-16 um) infrared solar spectra at anunapodized resolution of 0.01 cm(
      1) from space. The majority of the observations were obtained as exoatmospheric,
      near Sun center, absorption spectra, which were later ratioed to grazing
      atmospheric measurements to compute the atmospheric transmission of the Earth's
      atmosphere and analyzed for vertical profiles of minor and trace gases. Relative
      to the SPACELAB-3 mission that produced 4800 high Sun spectra (which were
      averaged into four grand average spectra), the ATLAS-3 mission produced some
      40,000 high Sun spectra (which have been similarly averaged) with an improvement
      in signal-to-noise ratio of a factor of 3-4 in the spectral region between 1000
      and 4800 cm(-1). A brief description of the spectral calibration and spectral
      quality is given as well as the location of electronic archives of these spectra.

PMID- 21085423
TI  - Calibration of planetary brightness temperature spectra at near-millimeter and
      submillimeter wavelengths with a Fourier-transform spectrometer.
AB  - A medium-resolution Fourier-transform spectrometer for ground-based observation
      of astronomical sources at near-millimeter and submillimeter wavelengths is
      described. The steps involved in measuring and calibrating astronomical spectra
      are elaborated. The spectrometer is well suited to planetary spectroscopy, and
      initial measurements of the intrinsic brightness temperature spectra of Uranus
      and Neptune at wavelengths of 1.0 to 1.5 mm are presented.

PMID- 21085424
TI  - Application of Doppler Michelson imaging to upper atmospheric wind measurement:
      WINDII and beyond.
AB  - A solid Doppler Michelson interferometer, consisting of different refractive
      plates cemented in the two arms of the interferometer, can be designed to be
      field widened, achromatic, and thermally stable. If the mirror in one arm is
      allowed to step over one wavelength about a fixed optical path difference, then
      phase-stepping interferometry can be used to determine the phase of an input
      spectral line. This is the basis of an optical Doppler interferometer used to
      measure upper atmospheric winds from space: the wind imaging interferometer
      (WINDII) on the Upper Atmosphere Research Satellite, UARS, which was launched on
      12 September 1991 and is still operating in orbit. The instrument employs a CCD
      imager to record a sequence of images at different phase steps from which images
      of optical emission rate, wind, and temperature are derived. The WINDII concept
      is reviewed, and its implementation is described. The performance in orbit is
      then reviewed, and a summary of some of the geophysical results is given.
      Finally, some suggestions for future applications of this concept are presented.

PMID- 21085425
TI  - Remote sensing of the Earth's atmosphere from space with high-resolution Fourier
      transform spectroscopy: development and methodology of data processing for the
      Atmospheric Trace Molecule Spectroscopy experiment.
AB  - The methodology of spectroscopic remote sensing with high-resolution Fourier
      transform spectra obtained from low Earth orbit by the Atmospheric Trace Molecule
      Spectroscopy (ATMOS) experiment is discussed. During the course of the
      Atmospheric Laboratory for Applications and Science (ATLAS) shuttle missions
      (1992-1994) a flexible, yet reproducible, retrieval strategy was developed that
      culminated in the near-real-time processing of telemetry data into vertical
      profiles of atmospheric composition during the ATLAS-3 mission. The development,
      evolution, robustness, and validation of the measurements are presented and
      assessed with a summary comparison of trace-gas observations within the Antarctic
      polar vortex in November 1994.

PMID- 21085427
TI  - Calibrated 0.1-cm(-1) IR emission spectra from 80 degrees N.
AB  - Spectra from a 0.1-cm(-1) resolution absolutely calibrated emission
      interferometer installed near Eureka, Northwest Territories, Canada (80 degrees
      N, 86 degrees W), at the Arctic Stratospheric Observatory are presented. The
      Michelson-type interferometer has a maximum path difference of 10 cm and uses a
      liquid-N(2)-cooled HgCdTe detector, which covers the spectral region from 650 to
      1250 cm(-1). Spectral intervals containing CO(2), HNO(3), and ozone have been
      modeled with a line-by-line radiative-transfer code and column amounts retrieved
      for the latter two constituents. The instrument and initial measurements are
      described.

PMID- 21085426
TI  - Remote sensing of vertical profiles of atmospheric trace constituents with MlPAS
      limb-emission spectrometers.
AB  - A deeper understanding of long-term ozone trends and periods of significant ozone
      depletion as well as of the anthropogenic greenhouse effect requires the
      concerted actions of experimenters and modelers. With respect to observations,
      atmospheric constituents need to be measured simultaneously and on a global
      basis. Fourier-transform infrared spectrometers are especially suited for this
      measurement task. Apromising and challenging branch of Fourier-transform infrared
      spectroscopy is its application to limb-emission sounding by the use of cryogenic
      instrumentation. This method allows the measurements to be made independently of
      the time of the day. The MIPAS (Michelson interferometer for passive atmospheric
      sounding) balloon-borne (MIPAS-B) and space-based (MIPAS-S) experiments apply
      this technique. While the MIPAS-B instrument has already been used for several
      years for stratospheric process studies, the MIPAS-S instrument is in development
      for the European Space Agency's ENVISAT mission. Instrumental aspects of these
      MIPAS experiments are highlighted, the most important results in ozone research
      achieved with MIPAS-B are reviewed, and a brief overview of the scientific
      capabilities of the MIPAS space experiment is given.

PMID- 21085428
TI  - Determination of trace-gas amounts in plumes by the use of orthogonal digital
      filtering of thermal-emission spectra.
AB  - The thermal emission of gases in a plume can be measured by a Fourier-transform
      spectrometer that is located some distance from the plume. In order to measure
      quantitatively the amount of a particular gas of interest, in general a large
      spectrally structured background must be removed. Differencing techniques, in
      which a measured background spectrum is subtracted from a measured spectrum
      believed to contain a target, often do not remove background spectral features
      adequately. The inadequacy of two-spectrum differencing techniques is due to the
      spatial and the temporal variations in a scene. We present a method by which to
      reduce spatial and temporal spectral clutter to instrument random noise, allowing
      the measurement of gas amounts in an effluent plume. The method is applied to
      simulated data and field data to show its effectiveness.

PMID- 21085429
TI  - Pressure sounding of the middle atmosphere from ATMOS solar occultation
      measurements of atmospheric CO(2) absorption lines.
AB  - A method for retrieving the atmospheric pressure corresponding to the tangent
      point of an infrared spectrum recorded in the solar occultation mode is described
      and applied to measurements made by the Atmospheric Trace Molecule Spectroscopy
      (ATMOS) Fourier-transform spectrometer. Tangent pressure values are inferred from
      measurements of isolated CO(2) lines with temperature-insensitive strengths by
      measuring the slant-column CO(2) amount and by adjusting the viewing geometry
      until the calculated column matches the observed column. Tangent pressures are
      determined with a spectroscopic precision of l%-3%, corresponding to a tangent
      point height precision of 70-210 m. The total uncertainty is limited primarily by
      the quality of the spectra and ranges between 4% and 6% (280-420 m) for spectra
      with signal-to-noise ratios of 300:1 and between 4% and 10% for spectra with
      signal-to-noise ratios of 100:1. The retrieval of atmospheric pressure increases
      the accuracy of the retrieved-gas concentrations by minimizing the effect of
      systematic errors introduced by climatological pressure data, ephemeris
      parameters, and the uncertainties in instrumental pointing.

PMID- 21085430
TI  - University of Denver infrared spectral atlases.
AB  - Atmospheric and laboratory atlases of high-resolution infrared absorption spectra
      have been generated from data obtained with the University of Denver Michelson
      type interferometer balloon-borne spectrometer systems. The main objectives of
      the atlas work have been the identification and the detailed analysis of
      stratospheric infrared high-resolution spectral features. The stratospheric
      atlases cover many spectral intervals and provide tables of line positions and
      species identifications. High Sun spectra are used for identification of solar
      lines. Latest editions of these atlases include selected sections in the 760-1950
      and 800-1700-cm(-1) regions at 0.02- and 0.002-cm(-1) resolutions, respectively.
      In addition to the stratospheric atlases, ground-based and laboratory spectral
      atlases have also been produced. The laboratory spectra of many molecules
      relevant to stratospheric chemistry have been obtained. A number of ongoing
      spectroscopic studies have been developed on the basis of the atlas work,
      including studies of solar and atmospheric spectral features.

PMID- 21085431
TI  - 1995 Atmospheric Trace Molecule Spectroscopy (ATMOS) linelist.
AB  - The Atmospheric Trace Molecule Spectroscopy (ATMOS) experiment uses a Fourier
      transform spectrometer on board the Space Shuttle to record infrared solar
      occultation spectra of the atmosphere at 0.01-cm(-1) resolution. The current
      version of the molecular spectroscopic database used for the analysis of the data
      obtained during three Space Shuttle missions between 1992 and 1994 is described.
      It is an extension of the effort first described by Brown et al. [Appl. Opt. 26,
      5154 (1987)] to maintain an up-to-date database for the ATMOS experiment. The
      three-part ATMOS compilation contains line parameters of 49 molecular species
      between 0 and 10000 cm(-1). The main list, with nearly 700,000 entries, is an
      updated version of the HITRAN 1992 database. The second compilation contains
      supplemental line parameters, and the third set consists of absorption cross
      sections to represent the unresolvable features of heavy molecules. The
      differences between the ATMOS database and other public compilations are
      discussed.

PMID- 21085432
TI  - Time-resolved Fourier spectroscopy for activated optical materials.
AB  - A low-cost add-on to commercial Fourier-transform spectrometers that have a
      continuously scanning Michelson interferometer has been developed for high
      resolution, broadband, time-resolved spectroscopy. A number of innovations have
      been implemented to enable near-IR, visible, and UV photolumi-nescence studies.
      These include error correction and normalization of interferogram points to
      correct for laser intensity variations and missed shots, reduction of mirror
      speed variations with recognition and avoidance of the timing mistakes they
      cause, and simple white-light-interferogram advancement optics that leave high
      frequency modulation efficiency for the signal of interest unchanged in
      dynamically aligned systems. Application to energy-transfer phenomena in solid
      state-laser media is described.

PMID- 21085433
TI  - Fast time-resolved Fourier-transform spectroscopy for the study of transient
      chemical reactions.
AB  - We describe the most recent implementation of the data acquisition system which
      we have developed for fast time-resolved (FTR) Fourier transform spectroscopy
      (FTS) and report spectra that were obtained by using this instrument. This FTRPTS
      data system operates in conjunction with any continuous-scan Michelson
      interferometer, giving it the capability to record many time-delayed spectra of a
      transient event, with a minimum time resolution of 1 us. The sensitivity and the
      spectral resolution of the complete system are the same as those that would be
      obtained if the interferometer were used in conventional steady-state
      spectroscopy. To illustrate the performance of the FTRPTS system, we recorded
      emission spectra from the products of transient chemical reactions of H atoms
      with CF(3)Cl, CF(2)Cl(2), CFCL(3), and NO(2). These are laser-initiated reactions
      involving atoms with energies that correspond to a temperature of approximately
      27,000 K and lifetimes of a few microseconds, but the FTRPTS system records the
      time evolution of their products with high signal-to-noise ratio.

PMID- 21085434
TI  - High-resolution Fourier spectrometry of N(2)(+).
AB  - A new perturbation analysis of the first negative system B(2)Sigma(u)(+) ?
      X(2)Sigma(g)(+) of the (14)N(2)(+) ion is performed based on spectra excited both
      at low and high temperatures by the use of either a hollow-cathode or a
      Pointolite lamp. Preliminary results are given for a deperturbation of the
      B(2)Sigma(u)(+) (nu = 0, nu = 1) levels. Deperturbed molecular constants and
      parameters that describe the B(2)Sigma(u)(+) ~ A(2)?(u) interaction are derived.

PMID- 21085435
TI  - Fourier transform spectroscopy of LaS in the infrared.
AB  - We recorded the emission spectrum of diatomic lanthanum sulfide on the Los Alamos
      Fourier transform spectrometer. In the region 7500-16,000 cm(-1), we identified
      over 120 bands and assigned them to the A(2)?(r)-X(2)Sigma(+) and B(2)Sigma(+)
      X(2)Sigma(+) transitions. Each of these bands is four headed.

PMID- 21085436
TI  - High-resolution Fourier-transform emission spectroscopy of the A(1)II
      X(1)Sigma(+) system of AIH.
AB  - The emission spectrum of the A(1)II-X(1)Sigma(+) system of AIH, excited in a
      hollow-cathode discharge lamp, has been observed at high resolution with a
      Fourier-transform spectrometer. The rotational lines in the 0-0 and the 1-1 bands
      have been measured with a precision of +/-0.001 cm(-1). The present measurements
      provide a considerable improvement overthe previous data of Zeeman and Ritter
      [Can. J. Phys. 32, 555 (1954)]. The present data, combined with the previous high
      resolution measurements of the 1-0 vibration-rotation band by White et al. [J.
      Chem. Phys. 99, 8371 (1993)] and the J = 1-0 pure rotational line of Goto and
      Saito [Astrophys. J. 452, L147 (1995)] have been used to determine improved
      molecular constants for the A(1)!! state.

PMID- 21085437
TI  - Variable-temperature 3-m absorption cell developed for spectroscopic measurements
      of gases.
AB  - A variable-temperature absorption cell 3 m in length, which was designed and
      built for spectroscopic measurements of gases in combination with a Bruker IPS
      120 HR interferometer, is described. The cell is surrounded by a cooling system
      and a heating system. The heating system consists of a computer-controlled set of
      16 independent heating elements distributed over the length of the cell. The
      entire assembly enables measurements to be made in the temperature range from 123
      to 423 K. The temperature of the cell can be stabilized within +/-0.5 K over the
      entire length in this temperature range. The performance of the cell is discussed
      in relation to a spectroscopic temperature determination by the use of CO(2)
      intensity measurements.

PMID- 21085438
TI  - New approach to high-precision Fourier transform spectrometer design.
AB  - Laser fringes have long been used to establish the x axis in interferometric
      spectrometry, but solutions for the intensity axis have been less satisfactory.
      Now we are seeing the rapid commercial development of low-cost, medium-speed,
      sigma-delta analog-to-digital converters developed for stereo audio applications.
      A single chip provides two channels of 20-bit precision at 50 kHz, a significant
      improvement over many current systems of much greater cost and complexity. But
      while the laser works in the spatial domain, this converter operates strictly in
      the time domain; it cannot be triggered. I have developed a bridge between these
      two domains, the adaptive digital filter, which not only permits us to use this
      converter to obtain measurements at arbitrary times but as a bonus shows us how
      to move much of the complexity of an interferometric-control and data-acquisition
      system from hardware to software. For example, flexible fringe subdivision (to
      increase the free spectral range) is easily obtained with a simple and efficient
      algorithm, completely free of laser ghosts. Compensation for drive velocity
      variation is also possible, requiring only a modest increase in computer memory.

PMID- 21085439
TI  - Infrared single-mode fiber-optic Fourier-transform spectrometry and double
      Fourier interferometry.
AB  - An infrared single-mode fiber-optic Fourier-transform spectrometer constructed
      for the demonstration of the technique is described, in which beam splitting and
      beam combining are performed with fiber-optic directional couplers and the
      optical path difference scan is generated by stretching fibers. Experiments done
      with this fiber-optic Fourier-transform spectrometer are presented. A spectral
      resolution of 1328 at 2.2 um can be achieved. The experimental results show the
      feasibility of fiber-optic Fourier-transform spectrometry and double Fourier
      interferometry.

PMID- 21085440
TI  - Digital array scanned interferometer: sensors and results.
AB  - Digital array scanned interferometers (DASI) blend characteristics of a grating
      spectrometer and a two-beam interferometer for acquisition of hyperspectra.
      DASI's posses field-widened capabilities that permit very high throughput.
      Aspects of DASI design, hyperspectra, and data processing methods are presented.
      In particular, we provide data showing that photon-noise-limited hyperspectra are
      achievable for DASI data.

PMID- 21085441
TI  - Folded-beam design for a Martin-Puplett interferometer with substrate polarizers.
AB  - A polarizing interferometer requires a rotation of 45 degrees  between the input
      polarizer and beam-splitter polarizer. If substrate polarizers are used, however,
      the p polarization should be transmitted at both polarizers for highest
      efficiency. An out-of-plane configuration is presented that satisfies both
      criteria.

PMID- 21085442
TI  - ERWIN: an E-region wind interferometer.
AB  - A field-widened Michelson interferometer designed to measure upper atmospheric
      winds at three altitudes near the mesopause by using airglow emissions from
      O(1)S, OH, and O(2) is described. A very large path difference (11 cm) is used to
      suppress the fringes from the hot F-region emission of O(1)S and to facilitate
      accurate measurements. Field widening and thermal compensation are achieved over
      the large spectral range (557.7-866.0 nm) by the use of three types of glass in
      the interferometer's arms. The instrument was installed at Resolute Bay, Canada
      (74.3 N, 94.5 W), in November 1992 and has been operated remotely from Toronto
      for four winter seasons. Some examples of data are shown to illustrate ERWIN's
      performance.

PMID- 21085443
TI  - Electromechanical linear actuators for Fourier transform spectrometers: a concept
      for extended range, high-resolution, solid-state actuators.
AB  - A piezoelectric effect device is reported that provides highly controllable,
      extended linear motion in an easily usable package. Recent advances in materials,
      materials processing, and piezoelectric mechanics have been synthesized to
      demonstrate an all-solid-state electromechanical actuator for Fourier transform
      spectrometer mirror position control. This actuator is inherently linear and is
      therefore a major improvement in efficiency, size, and mass over motors and lead
      screws, which require conversion from rotary to linear actuation. Velocity
      control of 1% has been demonstrated over a range of 0.5 cm at a velocity of 1
      cm/s. Scaling to a range of 4 cm and a velocity of 4 cm/s is discussed and
      currently appears feasible.

PMID- 21085444
TI  - Bilayer free-standing beam splitter for Fourier transform infrared spectrometry.
AB  - We describe the design, fabrication, testing, and performance of a two-layer free
      standing beam splitter for use in far-infrared Fourier transform infrared
      spectrometers. This bilayer beam splitter, consisting of a low-index polymer
      layer in combination with a high-index semiconductor layer, has an efficiency
      that is higher than that of the best combination of four single-layer Mylar beam
      splitters currently in use for spectrometry from 50 to 550 cm(-1).

PMID- 21085445
TI  - New designs for far-infrared beam splitters.
AB  - We explore theoretically the design of multilayer beam splitters for the far
      infrared that are based on coated pellicles as well as on solid substrates. The
      specific design criterion considered is as high a value as possible of the
      efficiency E = 4RT throughout the 10-140-um spectral region. Here R and T are the
      reflectance and the transmittance of the beam splitter, respectively. In the
      numerical study the refractive indices of the substrates and coating materials
      varied between 1.50 and 4.00. To survey the range of designs, we make a number of
      simplifying assumptions, the significance of which is later investigated. Various
      potential manufacturing problems are considered. It is shown that the performance
      of the beam splitters is not sensitive to the accuracy with which the layer
      thicknesses can be controlled. However, it does depend strongly on the lowest
      available refractive index of the coating materials. The performance is
      particularly sensitive to the extinction coefficients of solid substrate
      materials. Multilayer designs presented should be useful for use in Fourier
      transform spectrometers, as well as in other applications that do not require as
      high a spectral resolution.

PMID- 21085446
TI  - Ghosts and artifacts in Fourier-transform spectrometry.
AB  - Ghosts in Fourier-transform spectrometry are important for three reasons: they
      can give rise to spurious coincidences of frequency differences in spectral
      analysis, distort the phase correction, and set a limit to the attainable signal
      to-noise ratio. The various types of ghost, originating from amplitude
      modulation, phase modulation, and intermodulation, are described and discussed,
      together with some hardware and software artifacts. Recipes are given for
      identifying these features and, where possible, avoiding harmful effects from
      them.

PMID- 21085447
TI  - Phase determination from mostly one-sided interferograms.
AB  - We show how to detect and correct for nonlinear phase shifts in a mainly one
      sided interferogram of an emission-line source. We simultaneously detect and
      correct for an out-of-phase emission background from the spectrometer. The method
      requires two auxiliary spectra, one of a strong continuum source, and one of an
      emission-line source with little or no continuum.

PMID- 21085448
TI  - Practical wavelength calibration considerations for UV-visible Fourier-transform
      spectroscopy.
AB  - The intrinsic wavelength scale in a modern reference laser-controlled Michelson
      interferometer-sometimes referred to as the Connes advantage-offers excellent
      wavelength accuracy with relative ease. Truly superb wavelength accuracy, with
      total relative uncertainty in line position of the order of several parts in
      10(8), should be within reach with single-point, multiplicative calibration. The
      need for correction of the wavelength scale arises from two practical effects:
      the use of a finite aperture, from which off-axis rays propagate through the
      interferometer, and imperfect geometric alignment of the sample beam with the
      reference beam and the optical axis of the moving mirror. Although an analytical
      correction can be made for the finite-aperture effect, calibration with a trusted
      wavelength standard is typically used to accomplish both corrections. Practical
      aspects of accurate calibration of an interferometer in the UV-visible region are
      discussed. Critical issues regarding accurate use of a standard external to the
      sample source and the evaluation and selection of an appropriate standard are
      addressed. Anomalous results for two different potential wavelength standards
      measured by Fabry-Perot interferometry (Ar II and (198)Hg I) are observed.

PMID- 21085449
TI  - Determination of line strengths by Fourier-transform spectroscopy.
AB  - A rigorous test of the photometric accuracy of commercial high-resolution Fourier
      transform spectrometers has been made by measuring line strengths in the pure
      rotational spectrum of carbon monoxide. Measurements have been made with a Bruker
      IPS 120 HR spectrometer (transitions: J" = 7 . . . 23) and a Bomen DA3.002
      spectrometer (J" = 27 . . . 35). A least-squares fit of individual data sets and
      the combined data gave permanent electric dipole moments in the range 0.1091
      0.1101 D and quadratic Herman-Wallis factors in the range -0.188 to -0.229 * 10(
      3), in good agreement with literature values within the overall uncertainty.
      Sources of systematic errors in the Fourier-transform spectrometer and in the
      algorithms used to reduce the data are discussed in detail. The experimental
      results show that such errors affected the retrieved line strengths by less than
      1%.

PMID- 21085450
TI  - Single-photon detection beyond 1 um: performance of commercially available
      InGaAs/lnP detectors.
AB  - Commercially available InGaAs/lnP avalanche photodiodes, designed for optical
      receivers and range finders, can be operated biased above the breakdown voltage,
      achieving single-photon sensitivity. We describe in detail how to select the
      device for photon-counting applications among commercial samples. Because of the
      high dark-counting rate the detector must be cooled to below 100 K and operated
      in a gated mode. We achieved a noise equivalent power of 3 * 10(-16) W/Hz(1/2) to
      a 1.55-um wavelength and a time resolution well below 1 ns with a best value of
      200-ps FWHM. Finally we compare these figures with the performance of state-of
      the-art detectors in the near IR, and we highlight the potentials of properly
      designed InGaAs/lnP avalanche photodiodes in single-photon detection.

PMID- 21085451
TI  - Interferometric measurement of the refractive-index gradient distribution in
      gradient-index optical blanks.
AB  - Anew interferometric method for measuring the refractive-index distribution in a
      plane-parallel section cut from a gradient-index lens blank is described. A
      standard double-pass interferometric scheme modified to provide a single pass of
      the beam through the investigated gradient-index sample is used. The two
      dimensional variation of the refractive index in dimensions transverse to the
      sample surface is measured with an accuracy of better than 1 * 10(-4).

PMID- 21085452
TI  - Dispersed fringe tracking with the multi-r(0) apertures of the Grand
      Interferometre a 2 Telescopes.
AB  - A new fringe tracker based on photon-counting detectors and real-time image
      processing has been implemented on the Grand Interferometre a 2 Telescopes at the
      Observatoire de la Cote d'Azur. Fringe visibilities have been recorded on P Cygni
      and other stars across the Halphaemission line with optical path differences
      stabilized to between 4 and 7 um rms (1% of the coherence length). We present our
      initial results and describe the principle, implementation, and performance of
      the fringe tracker.

PMID- 21085453
TI  - Distance measurements using two frequency-stabilized Nd:YAG lasers.
AB  - Two diode-pumped tunable Nd:YAG lasers locked to sub-Doppler transitions of
      (127)I(2) and (133)Cs(2) are used as a source for two-wavelength interferometry.
      The synthetic wavelength is highly stable and accurate, owing to the frequency
      stability of the locked lasers and the precise determination of the frequency
      difference between Cs(2) and I(2) transitions. The dense spectra of the two
      molecular absorbers allows selection of synthetic wavelength A over a wide range,
      between 8.5 mm and more than 1 m, thus enabling distance measurements with a
      large nonambiguity range. Fringe contrast and phase-shifting methods are used to
      measure the synthetic phase. An accuracy of 70 um is achieved for synthetic
      wavelength Lambda ~ 19 mm, corresponding to a phase interpolation accuracy
      ofLambda/260.

PMID- 21085454
TI  - Ferroelectric liquid-crystal waveguide modulation based on a switchable uniaxial
      uniaxial interface.
AB  - Liquid crystals have effective electro-optic coefficients that are orders of
      magnitude larger than other integrated optical materials such as lithium niobate.
      However, previous studies of liquid-crystal waveguides have mainly focused on
      nematic liquid crystals, which exhibit impractically large scattering losses as
      waveguides. Studies of smectic liquid crystals and liquid crystals under strong
      confinement suggest the losses in these materials may be more manageable. In this
      study, the possibility of using ferroelectric liquid crystals in active waveguide
      modulators is explored through the analysis of several modulator configurations:
      a cutoff modulator, a deflection modulator, and an input coupler. As a way to
      study these structures, a mode-matching technique was developed to analyze the
      effects of a discontinuity in a uniaxial slab waveguide whose optic axis is in
      the plane of the waveguide. The results from the mode-matching technique were
      compared with those from simple bulk models. The analysis shows that
      ferroelectric liquid-crystal modulators have many desirable performance
      characteristics and could form the basis for practical waveguide modulators.

PMID- 21085456
TI  - Radiometric description of intensity and coherence in generalized holographic
      axicon images.
AB  - The characteristics of extended-range focal-line images generated in partially
      coherent light by annular-aperture logarithmic axicons are analyzed in terms of a
      certain generalized radiometric model. This radiometric description, which makes
      use of radiance propagation along geometric rays, is valid in the asymptotic
      short-wavelength limit, and it yields both the spectral density and the spatial
      coherence distributions of the images. The radio metrically obtained values on
      the image axis and in transverse planes are assessed against direct partially
      coherent wave-theoretical calculations. It is shown that the radiometric
      technique produces remarkably accurate results for the intensity and the spatial
      coherence profiles. Compared with diffraction calculations, the radiometric
      method is much faster, especially in conditions of relatively incoherent
      illumination.

PMID- 21085455
TI  - Temperature dependence of the birefringence of optical-disk substrates.
AB  - Injection-molded polycarbonate substrates are used predominantly in read-only,
      write-once, phase-change and magneto-optic disks for data storage. The in-plane
      and vertical birefringences of these substrates adversely affect the performance
      of optical data-storage systems. The disks are typically expected to operate in
      the ambient temperature range of 5-50  degrees C. We have investigated the
      behavior of the in-plane and vertical birefringences of a polycarbonate disk
      substrate in this temperature range using a custom-built ellipsometer. This study
      reveals that the in-plane birefringence changes dramatically within the
      investigated range of temperatures, whereas the vertical birefringence remains
      essentially constant. We suspect that the change in birefringence is due
      primarily to thermally induced stress in the substrate.

PMID- 21085457
TI  - Low-reflection-loss attenuator optical coatings: theory and experiment.
AB  - Following the optical admittance matching approach, we have derived explicit
      equations to evaluate the refractive index and thickness of the matching
      dielectric layer deposited on an attenuator layer to obtain zero or near-zero
      reflection loss at one or more than one wavelength. With these equations a new
      family of optical coatings that can not only attenuate the input optical
      radiation to a required level but can also show a very low reflection loss (less
      than 0.1%) within a specified band is successfully designed and developed.
      Typical coatings, produced by electron-beam evaporation, have an average
      reflection loss of less than 1% and transmittance of 0.42 and 0.64 +/- 0.02 over
      visible and near-IR spectral regions, respectively.

PMID- 21085458
TI  - Spectral transmittance of organic dye-doped glass films obtained by the solgel
      method.
AB  - The spectral transmittance of colored glass films synthesized by the solgel
      method is presented. The film was formed on a glass slide by dipping it into an
      organic dye-doped solution and, thereafter, by putting it into a furnace for
      solidification. Three dyes, Methylene Blue, Eosin, and Uranine, were used that
      exhibit transparent blue, pink, and yellow colors, respectively, when they are
      dissolved in the starting solution. We clarify how the spectral transmittance of
      the films varies with the solidification temperature. The films doped with two of
      the three dyes that exhibit violet, orange, and green colors are also
      synthesized, and their transmittance is measured. Moreover, the chemical
      durability of the films and the transmittance change caused by aging and
      illumination are examined.

PMID- 21085459
TI  - Calculation and optimization of Narcissus using paraxial ray tracing.
AB  - The Narcissus effect occurs in IR optical systems that employ a cooled quantum
      detector and can degrade the image quality very severely. Therefore, it is
      essential that it is controlled in the design stage. A detailed description is
      given of how Narcissus can be calculated, by the use of a routine based on
      paraxial ray tracing, and reduced automatically and simultaneously with the
      system aberrations, by inclusion of its results in the merit function of a damped
      least-squares optimization program.

PMID- 21085460
TI  - Resolution-enhanced detection of moving objects embedded within scattering media
      using time-gated speckle methods.
AB  - The holographic first-arriving-light method in combination with the speckle
      differencing method is used to provide resolution-enhanced detection of moving
      objects embedded in scattering media. Results show that the first-arriving-light
      technique provides significant resolution improvements over standard speckle
      differencing.

PMID- 21085461
TI  - Maximum far-field divergence angle of a plane source.
AB  - The far-field properties of a plane source with a constant phase distribution are
      presented. It is found, for the first time to our knowledge, that for any plane
      source the theoretical upper limit of the far-field divergence angle is shown to
      be 65.5 degrees . This result is different from what previous propagation and
      diffraction theories predicted, and when the size of the source approaches zero,
      the far-field behavior of the plane source is also different from a spherical
      wave in half-space.

PMID- 21085462
TI  - Transmission gratings for beam sampling and beam splitting.
AB  - Transmission gratings have rarely been used for beam sampling because they
      require special properties from dielectric overcoatings, which, to the best of
      our knowledge, are described here for the first time. Although such gratings are
      often used as beam splitters, their nature can be modified along the same
      principles with thin metal coatings, which are described.

PMID- 21085463
TI  - Diffuse reflectance and transmittance spectra of an interference layer: 1. Model
      formulation and properties: errata.

PMID- 21085464
TI  - A geometrical model for DNA organization in bacteria.
AB  - Recent experimental studies have revealed that bacteria, such as C. crescentus,
      show a remarkable spatial ordering of their chromosome. A strong linear
      correlation has been found between the position of genes on the chromosomal map
      and their spatial position in the cellular volume. We show that this correlation
      can be explained by a purely geometrical model. Namely, self-avoidance of DNA,
      specific positioning of one or few DNA loci (such as origin or terminus) together
      with the action of DNA compaction proteins (that organize the chromosome into
      topological domains) are sufficient to get a linear arrangement of the chromosome
      along the cell axis. We develop a Monte-Carlo method that allows us to test our
      model numerically and to analyze the dependence of the spatial ordering on
      various physiologically relevant parameters. We show that the proposed
      geometrical ordering mechanism is robust and universal (i.e. does not depend on
      specific bacterial details). The geometrical mechanism should work in all
      bacteria that have compacted chromosomes with spatially fixed regions. We use our
      model to make specific and experimentally testable predictions about the spatial
      arrangement of the chromosome in mutants of C. crescentus and the growth-stage
      dependent ordering in E. coli.

PMID- 21085465
TI  - The effects of age on inflammatory and coagulation-fibrinolysis response in
      patients hospitalized for pneumonia.
AB  - OBJECTIVE: To determine whether inflammatory and hemostasis response in patients
      hospitalized for pneumonia varies by age and whether these differences explain
      higher mortality in the elderly. METHODS: In an observational cohort of subjects
      with community-acquired pneumonia (CAP) recruited from emergency departments (ED)
      in 28 hospitals, we divided subjects into 5 age groups (<50, 51-64, 65-74, 75-84,
      and >=85). We measured circulating levels of inflammatory (TNF, IL-6, and IL-10),
      hemostasis (D-dimer, Factor IX, thrombin-antithrombin complex, antithrombin and
      plasminogen-activator inhibitor-1), and cell-surface markers (TLR-2, TLR-4, and
      HLA-DR) during the first week of hospitalization and at discharge and compared 90
      day mortality. We used logistic regression to compare odds ratios (OR) for 90-day
      mortality between age groups, adjusting for differences in pre-infection factors
      alone and then additionally adjusting for immune markers. RESULTS: Of 2,183
      subjects, 495, 444, 403, 583, and 258 subjects were <50, 51-64, 65-74, 75-84, and
      >=85 years of age, respectively. Large age-related differences were observed in
      90-day mortality (0.82% vs. 3.2% vs. 6.4% vs. 12.8% vs. 13.6%, p<0.01). No age
      related differences in inflammatory and cell surface markers occurred during the
      first week. Older subjects had higher pro-coagulant markers on ED presentation
      and over first week (p <= 0.03), but these differences were modest (1.0-1.7-fold
      differences). Odds of death for older adults changed minimally in models
      incorporating differences in hemostasis and inflammatory markers (for subjects >=
      85 compared to those <50, OR = 4.36, when adjusted for pre-infection factors and
      OR = 3.49 when additionally adjusted for hemostasis markers). At discharge,
      despite clinical recovery as evidenced by normal vital signs in >85% subjects,
      older subjects had modestly increased hemostasis markers and IL-6 levels
      (p<0.01). CONCLUSIONS: Modest age-related increases in coagulation response occur
      during hospitalization for CAP; however these differences do not explain the
      large differences in mortality. Despite clinical recovery, immune resolution may
      be delayed in older adults at discharge.

PMID- 21085466
TI  - High affinity human antibody fragments to dengue virus non-structural protein 3.
AB  - BACKGROUND: The enzyme activities catalysed by flavivirus non-structural protein
      3 (NS3) are essential for virus replication. They are distributed between the N
      terminal protease domain in the first one-third and the C-terminal
      ATPase/helicase and nucleoside 5' triphosphatase domain which forms the remainder
      of the 618-aa long protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, dengue
      full-length NS3 protein with residues 49 to 66 of NS2B covalently attached via a
      flexible linker, was used as bait in biopanning with a naive human Fab phage
      display library. Using a range of truncated constructs spanning the NS2B cofactor
      region and the full-length NS3, 10 unique Fab were identified and characterized.
      Of these, monoclonal Fab 3F8 was shown to bind alpha3" (residues 526 through 531)
      within subdomain III of the helicase domain. The antibody inhibits the ATPase and
      helicase activites of NS3 in biochemical assays and reduces DENV replication in
      HEK293 cells that were previously transfected with Fab 3F8 compared with mock
      transfected cells. CONCLUSIONS/SIGNIFICANCE: Antibodies such as 3F8 are valuable
      tools for studying the molecular mechanisms of flaviviral replication and for the
      monospecific detection of replicating dengue virus in vivo.

PMID- 21085467
TI  - Control of tungiasis through intermittent application of a plant-based repellent:
      an intervention study in a resource-poor community in Brazil.
AB  - BACKGROUND: Tungiasis, an ectoparasitosis caused by the female sand flea Tunga
      penetrans, is an important health problem in many impoverished communities in the
      tropics. Sand flea disease is associated with a broad spectrum of clinical
      pathology and severe sequels are frequent. Treatment options are limited.
      METHODOLOGY/PRINCIPAL FINDINGS: We assessed the effectiveness of the intermittent
      application of the plant-based repellent Zanzarin to reduce infestation intensity
      and tungiasis-associated morbidity in a resource-poor community in Brazil,
      characterized by a very high attack rate. The study population was randomized
      into three cohorts. Initially, during a period of four weeks, the repellent was
      applied twice daily to the feet of all cohort members. This reduced the number of
      embedded sandfleas to 0 in 98% of the participants. Thereafter members of cohort
      A applied the repellent every second week twice daily for one week, members of
      cohort B every fourth week for one week, and members of cohort C served as
      controls. Infestation intensity and tungiasis-associated morbidity were monitored
      during five months. The intermittent application of Zanzarin for one week every
      second week significantly reduced infestation intensity from a median 4 lesions
      (IQR 1-9) during the whole transmission season. In contrast, in cohort B
      (application of the repellent every fourth week) the infestation intensity
      remained twice as high (median 8 lesions, IQR 9-16; p = 0.0035), and in the
      control cohort C 3.5 times as high (median 14 lesions; IQR 7-26; p = 0.004 during
      the transmission season). Tungiasis-related acute pathology remained very low in
      cohort A (median severity score 2; IQR 1-4) as compared to cohort B (median
      severity score 5; IQR 3-7; p<0.001), and control cohort C (median severity score
      6.5; IQR 4-8; p<0.001). CONCLUSIONS/SIGNIFICANCE: Our study shows that in a
      setting with intense transmission, tungiasis-associated morbidity can be
      minimized through the intermittent application of a plant-based repellent.

PMID- 21085468
TI  - Impact of schistosome infection on Plasmodium falciparum Malariometric indices
      and immune correlates in school age children in Burma Valley, Zimbabwe.
AB  - A group of children aged 6-17 years was recruited and followed up for 12 months
      to study the impact of schistosome infection on malaria parasite prevalence,
      density, distribution and anemia. Levels of cytokines, malaria specific
      antibodies in plasma and parasite growth inhibition capacities were assessed.
      Baseline results suggested an increased prevalence of malaria parasites in
      children co-infected with schistosomiasis (31%) compared to children infected
      with malaria only (25%) (p = 0.064). Moreover, children co-infected with
      schistosomes and malaria had higher sexual stage geometric mean malaria parasite
      density (189 gametocytes/ul) than children infected with malaria only (73/ul
      gametocytes) (p = 0.043). In addition, a larger percentage of co-infected
      children (57%) had gametocytes as observed by microscopy compared to the malaria
      only infected children (36%) (p = 0.06). There was no difference between the two
      groups in terms of the prevalence of anemia, which was approximately 64% in both
      groups (p = 0.9). Plasma from malaria-infected children exhibited higher malaria
      antibody activity compared to the controls (p = 0.001) but was not different
      between malaria and schistosome plus malaria infected groups (p = 0.44) and
      malaria parasite growth inhibition activity at baseline was higher in the malaria
      only infected group of children than in the co-infected group though not reaching
      statistical significance (p = 0.5). Higher prevalence and higher mean gametocyte
      density in the peripheral blood may have implications in malaria transmission
      dynamics during co-infection with helminths.

PMID- 21085469
TI  - A comprehensive genetic analysis of candidate genes regulating response to
      Trypanosoma congolense infection in mice.
AB  - BACKGROUND: African trypanosomes are protozoan parasites that cause "sleeping
      sickness" in humans and a similar disease in livestock. Trypanosomes also infect
      laboratory mice and three major quantitative trait loci (QTL) that regulate
      survival time after infection with T. congolense have been identified in two
      independent crosses between susceptible A/J and BALB/c mice, and the resistant
      C57BL/6. These were designated Tir1, Tir2 and Tir3 for Trypanosoma infection
      response, and range in size from 0.9-12 cM. PRINCIPAL FINDINGS: Mapping loci
      regulating survival time after T. congolense infection in an additional cross
      revealed that susceptible C3H/HeJ mice have alleles that reduce survival time
      after infection at Tir1 and Tir3 QTL, but not at Tir2. Next-generation
      resequencing of a 6.2 Mbp region of mouse chromosome 17, which includes Tir1,
      identified 1,632 common single nucleotide polymorphisms (SNP) including a
      probably damaging non-synonymous SNP in Pram1 (PML-RAR alpha-regulated adaptor
      molecule 1), which was the most plausible candidate QTL gene in Tir1. Genome-wide
      comparative genomic hybridisation identified 12 loci with copy number variants
      (CNV) that correlate with differential gene expression, including Cd244 (natural
      killer cell receptor 2B4), which lies close to the peak of Tir3c and has gene
      expression that correlates with CNV and phenotype, making it a strong candidate
      QTL gene at this locus. CONCLUSIONS: By systematically combining next-generation
      DNA capture and sequencing, array-based comparative genomic hybridisation (aCGH),
      gene expression data and SNP annotation we have developed a strategy that can
      generate a short list of polymorphisms in candidate QTL genes that can be
      functionally tested.

PMID- 21085470
TI  - Adaptive immunity against Leishmania nucleoside hydrolase maps its c-terminal
      domain as the target of the CD4+ T cell-driven protective response.
AB  - Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and
      bacteria. They are vital protagonists in the establishment of early infection
      and, therefore, are excellent candidates for the pathogen recognition by adaptive
      immune responses. Immune protection against NHs would prevent disease at the
      early infection of several pathogens. We have identified the domain of the NH of
      L. donovani (NH36) responsible for its immunogenicity and protective efficacy
      against murine visceral leishmaniasis (VL). Using recombinant generated peptides
      covering the whole NH36 sequence and saponin we demonstrate that protection
      against L. chagasi is related to its C-terminal domain (amino-acids 199-314) and
      is mediated mainly by a CD4+ T cell driven response with a lower contribution of
      CD8+ T cells. Immunization with this peptide exceeds in 36.73+/-12.33% the
      protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a,
      IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-gamma secretion, ratios
      of IFN-gamma/IL-10 producing CD4+ and CD8+ T cells and percents of antibody
      binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated
      mice. The increases in DTH and in ratios of TNFalpha/IL-10 CD4+ producing cells
      were however the strong correlates of protection which was confirmed by in vivo
      depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes
      and a pronounced decrease in parasite load (90.5-88.23%; p = 0.011) that was long
      lasting. No decrease in parasite load was detected after vaccination with the N
      domain of NH36, in spite of the induction of IFN-gamma/IL-10 expression by CD4+ T
      cells after challenge. Both peptides reduced the size of footpad lesions, but
      only the C-domain reduced the parasite load of mice challenged with L.
      amazonensis. The identification of the target of the immune response to NH36
      represents a basis for the rationale development of a bivalent vaccine against
      leishmaniasis and for multivalent vaccines against NHs-dependent pathogens.

PMID- 21085471
TI  - Arbovirus detection in insect vectors by rapid, high-throughput pyrosequencing.
AB  - BACKGROUND: Despite the global threat caused by arthropod-borne viruses, there is
      not an efficient method for screening vector populations to detect novel viral
      sequences. Current viral detection and surveillance methods based on culture can
      be costly and time consuming and are predicated on prior knowledge of the
      etiologic agent, as they rely on specific oligonucleotide primers or antibodies.
      Therefore, these techniques may be unsuitable for situations when the causative
      agent of an outbreak is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we
      explored the use of high-throughput pyrosequencing for surveillance of arthropod
      borne RNA viruses. Dengue virus, a member of the positive strand RNA Flavivirus
      family that is transmitted by several members of the Aedes genus of mosquitoes,
      was used as a model. Aedes aegypti mosquitoes experimentally infected with dengue
      virus type 1 (DENV-1) were pooled with noninfected mosquitoes to simulate samples
      derived from ongoing arbovirus surveillance programs. Using random-primed
      methods, total RNA was reverse-transcribed and resulting cDNA subjected to 454
      pyrosequencing. CONCLUSIONS/SIGNIFICANCE: In two types of samples, one with 5
      adult mosquitoes infected with DENV-1- and the other with 1 DENV-1 infected
      mosquito and 4 noninfected mosquitoes, we identified DENV-1 DNA sequences. DENV-1
      sequences were not detected in an uninfected control pool of 5 adult mosquitoes.
      We calculated the proportion of the Ae. aegypti metagenome contributed by each
      infecting Dengue virus genome (p(IP)), which ranged from 2.75*10(-8) to 1.08*10(
      7). DENV-1 RNA was sufficiently concentrated in the mosquito that its detection
      was feasible using current high-throughput sequencing instrumentation. We also
      identified some of the components of the mosquito microflora on the basis of the
      sequence of expressed RNA. This included members of the bacterial genera
      Pirellula and Asaia, various fungi, and a potentially uncharacterized mycovirus.

PMID- 21085472
TI  - Atlantic leatherback migratory paths and temporary residence areas.
AB  - BACKGROUND: Sea turtles are long-distance migrants with considerable behavioural
      plasticity in terms of migratory patterns, habitat use and foraging sites within
      and among populations. However, for the most widely migrating turtle, the
      leatherback turtle Dermochelys coriacea, studies combining data from individuals
      of different populations are uncommon. Such studies are however critical to
      better understand intra- and inter-population variability and take it into
      account in the implementation of conservation strategies of this critically
      endangered species. Here, we investigated the movements and diving behaviour of
      16 Atlantic leatherback turtles from three different nesting sites and one
      foraging site during their post-breeding migration to assess the potential
      determinants of intra- and inter-population variability in migratory patterns.
      METHODOLOGY/PRINCIPAL FINDINGS: Using satellite-derived behavioural and
      oceanographic data, we show that turtles used Temporary Residence Areas (TRAs)
      distributed all around the Atlantic Ocean: 9 in the neritic domain and 13 in the
      oceanic domain. These TRAs did not share a common oceanographic determinant but
      on the contrary were associated with mesoscale surface oceanographic features of
      different types (i.e., altimetric features and/or surface chlorophyll a
      concentration). Conversely, turtles exhibited relatively similar horizontal and
      vertical behaviours when in TRAs (i.e., slow swimming velocity/sinuous
      path/shallow dives) suggesting foraging activity in these productive regions.
      Migratory paths and TRAs distribution showed interesting similarities with the
      trajectories of passive satellite-tracked drifters, suggesting that the general
      dispersion pattern of adults from the nesting sites may reflect the extent of
      passive dispersion initially experienced by hatchlings. CONCLUSIONS/SIGNIFICANCE:
      Intra- and inter-population behavioural variability may therefore be linked with
      initial hatchling drift scenarios and be highly influenced by environmental
      conditions. This high degree of behavioural plasticity in Atlantic leatherback
      turtles makes species-targeted conservation strategies challenging and stresses
      the need for a larger dataset (>100 individuals) for providing general
      recommendations in terms of conservation.

PMID- 21085473
TI  - Coevolution in a one predator-two prey system.
AB  - BACKGROUND: Our understanding of coevolution in a predator-prey system is based
      mostly on pair-wise interactions. METHODOLOGY AND PRINCIPAL FINDINGS: Here I
      analyze a one-predator-two-prey system in which the predator's attack ability and
      the defense abilities of the prey all evolve. The coevolutionary consequences can
      differ dramatically depending on the initial trait value and the timing of the
      alternative prey's invasion into the original system. If the invading prey
      species has relatively low defense ability when it invades, its defense is likely
      to evolve to a lower level, stabilizing the population dynamics. In contrast, if
      when it invades its defense ability is close to that of the resident prey, its
      defense can evolve to a higher level and that of the resident prey may suddenly
      cease to evolve, destabilizing the population dynamics. Destabilization due to
      invasion is likely when the invading prey is adaptively superior (evolution of
      its defense is less constrained and fast), and it can also occur in a broad
      condition even when the invading prey is adaptively inferior. In addition,
      invasion into a resident system far from equilibrium characterized by population
      oscillations is likely to cause further destabilization. CONCLUSIONS AND
      SIGNIFICANCE: An invading prey species is thus likely to destabilize a resident
      community.

PMID- 21085475
TI  - Utilization of the primary health care services in the Tshwane Region of Gauteng
      Province, South Africa.
AB  - BACKGROUND: In South Africa, the provision of primary health care is a basic
      service designed to be cost effective and bring healthcare as close as possible
      to the population, particularly to those people of low economic status. It is a
      service which is provided free of charge by the South African government and as
      part of the millennium health goals, it is intended that the service should be
      accessible to the populace and be effectively utilized. OBJECTIVE: This study was
      designed to investigate the accessibility and utilization of the primary health
      care services in three community health care centres in the Tshwane of the
      Gauteng Province, South Africa. METHODOLOGY: Data were obtained from participants
      attending three Community Health Care Centres in the Tshwane Region using self
      administered structured questionnaires. A document review of the Community Health
      Care Centres records was conducted to investigate the utilization trends of the
      services provided and descriptive statistics were used to analyze the data
      obtained. RESULTS: The results showed that the Community Health Care Centres in
      the Tshwane Region are accessible to most participants who lived within 5 km of
      such centres and who traveled 30 minutes or less to the clinic. Using a taxi or
      walking were found to be the most common means of transport used to gain access
      to such a clinic. The findings showed that generally, participants were satisfied
      with the services provided. CONCLUSION: Participants of this study have access to
      the community health care centres in the Tshwane Region and there seems to be
      effective utilization by patients attending them.

PMID- 21085474
TI  - Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) by tirapazamine is
      dependent on eIF2alpha phosphorylation rather than the mTORC1/4E-BP1 pathway.
AB  - Hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that
      mediates the adaptation of tumor cells and tissues to the hypoxic
      microenvironment, has attracted considerable interest as a potential therapeutic
      target. Tirapazamine (TPZ), a well-characterized bioreductive anticancer agent,
      is currently in Phase II and III clinical trials. A major aspect of the
      anticancer activity of TPZ is its identity as a tumor-specific topoisomerase
      IIalpha inhibitor. In the study, for the first time, we found that TPZ acts in a
      novel manner to inhibit HIF-1alpha accumulation driven by hypoxia or growth
      factors in human cancer cells and in HepG2 cell-derived tumors in athymic nude
      mice. We investigated the mechanism of TPZ on HIF-1alpha in HeLa human cervical
      cancer cells by western blot analysis, reverse transcription-PCR assay,
      luciferase reporter assay and small interfering RNA (siRNA) assay. Mechanistic
      studies demonstrated that neither HIF-1alpha mRNA levels nor HIF-1alpha protein
      degradation are affected by TPZ. However, TPZ was found to be involved in HIF
      1alpha translational regulation. Further studies revealed that the inhibitory
      effect of TPZ on HIF-1alpha protein synthesis is dependent on the phosphorylation
      of translation initiation factor 2alpha (eIF2alpha) rather than the mTOR complex
      1/eukaryotic initiation factor 4E-binding protein-1 (mTORC1/4E-BP1) pathway.
      Immunofluorescence analysis of tumor sections provide the in vivo evidences to
      support our hypothesis. Additionally, siRNA specifically targeting topoisomerase
      IIalpha did not reverse the ability of TPZ to inhibit HIF-1alpha expression,
      suggesting that the HIF-1alpha inhibitory activity of TPZ is independent of its
      topoisomerase IIalpha inhibition. In conclusion, our findings suggest that TPZ is
      a potent regulator of HIF-1alpha and provide new insight into the potential
      molecular mechanism whereby TPZ serves to reduce HIF-1alpha expression.

PMID- 21085476
TI  - Adipokine pattern in subjects with impaired fasting glucose and impaired glucose
      tolerance in comparison to normal glucose tolerance and diabetes.
AB  - AIM: Altered adipokine serum concentrations early reflect impaired adipose tissue
      function in obese patients with type 2 diabetes (T2D). It is not entirely clear
      whether these adipokine alterations are already present in prediabetic states and
      so far there is no comprehensive adipokine panel available. Therefore, the aim of
      this study was to assess distinct adipokine profiles in patients with normal
      glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose
      tolerance (IGT) or T2D. METHODS: Based on 75 g oral glucose tolerance tests, 124
      individuals were divided into groups of IFG (n = 35), IGT (n = 45), or NGT (n =
      43). Furthermore, 56 subjects with T2D were included. Serum concentrations of
      adiponectin, chemerin, fetuin-A, leptin, interleukin (IL)-6, retinol-binding
      protein 4 (RBP4), monocyte chemoattractant protein (MCP)-1, vaspin, progranulin,
      and soluble leptin receptor (sOBR) were measured by ELISAs. RESULTS: Chemerin,
      progranulin, fetuin-A, and RBP4, IL-6, adiponectin and leptin serum
      concentrations were differentially regulated among the four investigated groups
      but only circulating chemerin was significantly different in patients with IGT
      compared to those with IFG. Compared to T2D the IFG subjects had higher serum
      chemerin, progranulin, fetuin-A and RBP4 levels which was not detectable in the
      comparison of the T2D and IGT group. CONCLUSION: Alterations in adipokine serum
      concentrations are already detectable in prediabetic states, mainly for chemerin,
      and may reflect adipose tissue dysfunction as an early pathogenetic event in T2D
      development. In addition, distinct adipokine serum patterns in individuals with
      IFG and IGT suggest a specific role of adipose tissue in the pathogenesis of
      these prediabetic states.

PMID- 21085477
TI  - Muscle physiology changes induced by every other day feeding and endurance
      exercise in mice: effects on physical performance.
AB  - Every other day feeding (EOD) and exercise induce changes in cell metabolism. The
      aim of the present work was to know if both EOD and exercise produce similar
      effects on physical capacity, studying their physiological, biochemical and
      metabolic effects on muscle. Male OF-1 mice were fed either ad libitum (AL) or
      under EOD. After 18 weeks under EOD, animals were also trained by using a
      treadmill for another 6 weeks and then analyzed for physical activity. Both, EOD
      and endurance exercise increased the resistance of animals to extenuating
      activity and improved motor coordination. Among the groups that showed the
      highest performance, AL and EOD trained animals, ALT and EODT respectively, only
      the EODT group was able to increase glucose and triglycerides levels in plasma
      after extenuating exercise. No high effects on mitochondrial respiratory chain
      activities or protein levels neither on coenzyme Q levels were found in
      gastrocnemius muscle. However, exercise and EOD did increase beta-oxidation
      activity in this muscle accompanied by increased CD36 levels in animals fed under
      EOD and by changes in shape and localization of mitochondria in muscle fibers.
      Furthermore, EOD and training decreased muscle damage after strenuous exercise.
      EOD also reduced the levels of lipid peroxidation in muscle. Our results indicate
      that EOD improves muscle performance and resistance by increasing lipid
      catabolism in muscle mitochondria at the same time that prevents lipid
      peroxidation and muscle damage.

PMID- 21085478
TI  - Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in
      Cambodia.
AB  - BACKGROUND: Cryptococcal infection is a frequent cause of mortality in Cambodian
      HIV-infected patients with CD4+ count <=100 cells/ul. This study assessed the
      cost-effectiveness of three strategies for cryptococcosis prevention in HIV
      infected patients. METHODS: A MARKOV DECISION TREE WAS USED TO COMPARE THE
      FOLLOWING STRATEGIES AT THE TIME OF HIV DIAGNOSIS: no intervention, one time
      systematic serum cryptococcal antigen (CRAG) screening and treatment of positive
      patients, and systematic primary prophylaxis with fluconazole. The trajectory of
      a hypothetical cohort of HIV-infected patients with CD4+ count <=100 cells/ul
      initiating care was simulated over a 1-year period (cotrimoxazole initiation at
      enrollment; antiretroviral therapy within 3 months). Natural history and cost
      data (US$ 2009) were from Cambodia. Efficacy data were from international
      literature. RESULTS: In a population in which 81% of patients had a CD4+ count
      <=50 cells/ ul and 19% a CD4+ count between 51-100 cells/ul, the proportion alive
      1 year after enrollment was 61% (cost $ 472) with no intervention, 70% (cost $
      483) with screening, and 72% (cost $ 492) with prophylaxis. After one year of
      follow-up, the cost-effectiveness of screening vs. no intervention was US$
      180/life year gained (LYG). The cost-effectiveness of prophylaxis vs. screening
      was $ 511/LYG. The cost-effectiveness of prophylaxis vs. screening was estimated
      at $1538/LYG if the proportion of patients with CD4+ count <=50 cells/ul
      decreased by 75%. CONCLUSION: In a high endemic area of cryptococcosis and HIV
      infection, serum CRAG screening and prophylaxis are two cost effective strategies
      to prevent AIDS associated cryptococcosis in patients with CD4+ count <=100
      cells/ul, at a short-term horizon, screening being more cost-effective but less
      effective than prophylaxis. Systematic primary prophylaxis may be preferred in
      patients with CD4+ below 50 cells/ul while systematic serum CRAG screening for
      early targeted treatment may be preferred in patients with CD4+ between 51-100
      cells/ul.

PMID- 21085479
TI  - Improving a mother to child HIV transmission programme through health system
      redesign: quality improvement, protocol adjustment and resource addition.
AB  - BACKGROUND: Health systems that deliver prevention of mother to child
      transmission (PMTCT) services in low and middle income countries continue to
      underperform, resulting in thousands of unnecessary HIV infections of newborns
      each year. We used a combination of approaches to health systems strengthening to
      reduce transmission of HIV from mother to infant in a multi-facility public
      health system in South Africa. METHODOLOGY/PRINCIPAL FINDINGS: All primary care
      sites and specialized birthing centers in a resource constrained sub-district of
      Cape Metro District, South Africa, were enrolled in a quality improvement (QI)
      programme. All pregnant women receiving antenatal, intrapartum and postnatal
      infant care in the sub-district between January 2006 and March 2009 were included
      in the intervention that had a prototype-innovation phase and a rapid spread
      phase. System changes were introduced to help frontline healthcare workers to
      identify and improve performance gaps at each step of the PMTCT pathway.
      Improvement was facilitated and spread through the use of a Breakthrough Series
      Collaborative that accelerated learning and the spread of successful changes.
      Protocol changes and additional resources were introduced by provincial and
      municipal government. The proportion of HIV-exposed infants testing positive
      declined from 7.6% to 5%. Key intermediate PMTCT processes improved (antenatal
      AZT increased from 74% to 86%, PMTCT clients on HAART at the time of labour
      increased from 10% to 25%, intrapartum AZT increased from 43% to 84%, and
      postnatal HIV testing from 79% to 95%) compared to baseline.
      CONCLUSIONS/SIGNIFICANCE: System improvement methods, protocol changes and
      addition/reallocation of resources contributed to improved PMTCT processes and
      outcomes in a resource constrained setting. The intervention requires a clear
      design, leadership buy-in, building local capacity to use systems improvement
      methods, and a reliable data system. A systems improvement approach offers a much
      needed approach to rapidly improve under-performing PMTCT implementation
      programmes at scale in sub-Saharan Africa.

PMID- 21085481
TI  - Vision impairs the abilities of bats to avoid colliding with stationary
      obstacles.
AB  - BACKGROUND: Free-flying insectivorous bats occasionally collide with stationary
      objects they should easily detect by echolocation and avoid. Collisions often
      occur with lighted objects, suggesting ambient light may deleteriously affect
      obstacle avoidance capabilities. We tested the hypothesis that free-flying bats
      may orient by vision when they collide with some obstacles. We additionally
      tested whether acoustic distractions, such as "distress calls" of other bats,
      contributed to probabilities of collision. METHODOLOGY/PRINCIPAL FINDINGS: To
      investigate the role of visual cues in the collisions of free-flying little brown
      bats (Myotis lucifugus) with stationary objects, we set up obstacles in an area
      of high bat traffic during swarming. We used combinations of light intensities
      and visually dissimilar obstacles to verify that bats orient by vision. In early
      August, bats collided more often in the light than the dark, and probabilities of
      collision varied with the visibility of obstacles. However, the probabilities of
      collisions altered in mid to late August, coincident with the start of
      behavioural, hormonal, and physiological changes occurring during swarming and
      mating. Distress calls did not distract bats and increase the incidence of
      collisions. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that visual cues are
      more important for free-flying bats than previously recognized, suggesting
      integration of multi-sensory modalities during orientation. Furthermore, our
      study highlights differences between responses of captive and wild bats,
      indicating a need for more field experiments.

PMID- 21085480
TI  - Early acquisition of neural crest competence during hESCs neuralization.
AB  - BACKGROUND: Neural crest stem cells (NCSCs) are a transient multipotent embryonic
      cell population that represents a defining characteristic of vertebrates. The
      neural crest (NC) gives rise to many derivatives including the neurons and glia
      of the sensory and autonomic ganglia of the peripheral nervous system, enteric
      neurons and glia, melanocytes, and the cartilaginous, bony and connective tissue
      of the craniofacial skeleton, cephalic neuroendocrine organs, and some heart
      vessels. METHODOLOGY/PRINCIPAL FINDINGS: We present evidence that neural crest
      (NC) competence can be acquired very early when human embryonic stem cells
      (hESCs) are selectively neuralized towards dorsal neuroepithelium in the absence
      of feeder cells in fully defined conditions. When hESC-derived neurospheres are
      plated on fibronectin, some cells emigrate onto the substrate. These early
      migratory Neural Crest Stem Cells (emNCSCs) uniformly upregulate Sox10 and
      vimentin, downregulate N-cadherin, and remodel F-actin, consistent with a
      transition from neuroepithelium to a mesenchymal NC cell. Over 13% of emNCSCs
      upregulate CD73, a marker of mesenchymal lineage characteristic of cephalic NC
      and connexin 43, found on early migratory NC cells. We demonstrated that emNCSCs
      give rise in vitro to all NC lineages, are multipotent on clonal level, and
      appropriately respond to developmental factors. We suggest that human emNCSC
      resemble cephalic NC described in model organisms. Ex vivo emNCSCs can
      differentiate into neurons in Ret.k(-) mouse embryonic gut tissue cultures and
      transplanted emNCSCs incorporate into NC-derived structures but not CNS tissues
      in chick embryos. CONCLUSIONS/SIGNIFICANCE: These findings will provide a
      framework for further studying early human NC development including the
      epithelial to mesenchymal transition during NC delamination.

PMID- 21085482
TI  - Representation of cancer in the medical literature--a bibliometric analysis.
AB  - BACKGROUND: There exists a lack of knowledge regarding the quantity and quality
      of scientific yield in relation to individual cancer types. We aimed to measure
      the proportion, quality and relevance of oncology-related articles, and to relate
      this output to their associated disease burden. By incorporating the impact
      factor(IF) and EigenfactorTM(EF) into our analysis we also assessed the
      relationship between these indices and the output under study. METHODS: All
      publications in 2007 were retrieved for the 26 most common cancers. The top 20
      journals ranked by IF and EF in general medicine and oncology, and the presence
      of each malignancy within these titles was analysed. Journals publishing most
      prolifically on each cancer were identified and their impact assessed. PRINCIPAL
      FINDINGS: 63260 (PubMed) and 126845 (WoS) entries were generated, respectively.
      26 neoplasms accounted for 25% of total output from the top medical publications.
      5 cancers dominated the first quartile of output in the top oncology journals;
      breast, prostate, lung, and intestinal cancer, and leukaemia. Journals associated
      with these cancers were associated with much higher IFs and EFs than those
      journals associated with the other cancer types under study, although these
      measures were not equivalent across all sub-specialties. In addition, yield on
      each cancer was related to its disease burden as measured by its incidence and
      prevalence. CONCLUSIONS: Oncology enjoys disproportionate representation in the
      more prestigious medical journals. 5 cancers dominate yield, although this
      attention is justified given their associated disease burden. The commonly used
      IF and the recently introduced EF do not correlate in the assessment of the
      preeminent oncology journals, nor at the level of individual malignancies; there
      is a need to delineate between proxy measures of quality and the relevance of
      output when assessing its merit. These results raise significant questions
      regarding the best method of assessment of research and scientific output in the
      field of oncology.

PMID- 21085484
TI  - Standardizing clinical trials workflow representation in UML for international
      site comparison.
AB  - BACKGROUND: With the globalization of clinical trials, a growing emphasis has
      been placed on the standardization of the workflow in order to ensure the
      reproducibility and reliability of the overall trial. Despite the importance of
      workflow evaluation, to our knowledge no previous studies have attempted to adapt
      existing modeling languages to standardize the representation of clinical trials.
      Unified Modeling Language (UML) is a computational language that can be used to
      model operational workflow, and a UML profile can be developed to standardize UML
      models within a given domain. This paper's objective is to develop a UML profile
      to extend the UML Activity Diagram schema into the clinical trials domain,
      defining a standard representation for clinical trial workflow diagrams in UML.
      METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were
      examined to model their workflow and collect time-motion data. UML modeling was
      conducted in Eclipse, and a UML profile was developed to incorporate information
      used in discrete event simulation software. RESULTS: Ethnographic observation
      revealed bottlenecks in workflow: these included tasks requiring full commitment
      of CRCs, transferring notes from paper to computers, deviations from standard
      operating procedures, and conflicts between different IT systems. Time-motion
      analysis revealed that nurses' activities took up the most time in the workflow
      and contained a high frequency of shorter duration activities. Administrative
      assistants performed more activities near the beginning and end of the workflow.
      Overall, clinical trial tasks had a greater frequency than clinic routines or
      other general activities. CONCLUSIONS: This paper describes a method for modeling
      clinical trial workflow in UML and standardizing these workflow diagrams through
      a UML profile. In the increasingly global environment of clinical trials, the
      standardization of workflow modeling is a necessary precursor to conducting a
      comparative analysis of international clinical trials workflows.

PMID- 21085483
TI  - Cell-cycle inhibition by Helicobacter pylori L-asparaginase.
AB  - Helicobacter pylori (H. pylori) is a major human pathogen causing chronic
      gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue
      lymphoma. One of the mechanisms whereby it induces damage depends on its
      interference with proliferation of host tissues. We here describe the discovery
      of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both
      of gastric and non-gastric origin. An integrated approach was adopted to isolate
      and characterise the molecule from the bacterial culture filtrate produced in a
      protein-free medium: size-exclusion chromatography, non-reducing gel
      electrophoresis, mass spectrometry, mutant analysis, recombinant protein
      expression and enzymatic assays. L-asparaginase was identified as the factor
      responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its
      effect on cell-cycle was confirmed by inhibitors, a knockout strain and the
      action of recombinant L-asparaginase on cell lines. Interference with cell-cycle
      in vitro depended on cell genotype and was related to the expression levels of
      the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution
      of L-asparaginase was also analysed along with its immunogenicity. H. pylori L
      asparaginase is a novel antigen that functions as a cell-cycle inhibitor of
      fibroblasts and gastric cell lines. We give evidence supporting a role in the
      pathogenesis of H. pylori-related diseases and discuss its potential diagnostic
      application.

PMID- 21085485
TI  - Associations of serum 25-hydroxyvitamin D, parathyroid hormone and calcium with
      cardiovascular risk factors: analysis of 3 NHANES cycles (2001-2006).
AB  - BACKGROUND: Increasing evidence suggests a role for mineral metabolism in
      cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone
      (PTH), and calcium may be directly associated with cardiovascular risk factors or
      mediated by each other. METHODOLOGY/PRINCIPAL FINDINGS: We combined data for
      adult participants in three cycles of the National Health and Nutrition
      Examination Survey (2001-2, 2003-4, 2005-6), a representative sample of the
      civilian, non-institutionalized US population (N = 3,958). Using this data we
      examined joint associations of 25(OH)D, PTH and calcium with a range of
      cardiovascular risk factors. 25(OH)D was inversely associated with fasting
      insulin (mean difference in insulin per 1 standard deviation 25(OH)D: -0.053
      (95%CI: -0.091, -0.015)), glucose (-0.046 95%CI: -0.081, -0.012) and systolic
      blood pressure (SBP) (-0.032 95%CI: -0.062, -0.001), and positively associated
      with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148),
      after adjustment for ethnicity, smoking, socio-economic status and waist
      circumference. PTH was positively associated with diastolic blood pressure
      (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not
      associated with other cardiovascular risk factors. Albumin adjusted calcium was
      associated with triglycerides (0.102 95%CI: 0.063, 0.141), postload glucose
      (0.078, 95%CI: 0.025, 0.130), fasting insulin (0.074, 95%CI: 0.044, 0.104), HbA1c
      (0.070, 95%CI: 0.036, 0.105), SBP (0.064, 95%CI: 0.028, 0.100), fasting glucose
      (0.055, 95%CI: 0.018, 0.092) and low density lipoprotein cholesterol (0.052,
      95%CI: 0.014, 0.091). With mutual adjustment for each other, these associations
      remained essentially unchanged. CONCLUSIONS/SIGNIFICANCE: Lower levels of 25(OH)D
      and higher levels of calcium and PTH appear to be associated with different
      cardiovascular risk factors and may therefore affect cardiovascular disease risk
      through different mechanisms.

PMID- 21085486
TI  - Profiles of human serum antibody responses elicited by three leading HIV vaccines
      focusing on the induction of Env-specific antibodies.
AB  - In the current report, we compared the specificities of antibody responses in
      sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using
      different immunization regimens. HIV-1 Env-specific binding antibody,
      neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and
      profiles of antibody specificity were analyzed for human immune sera collected
      from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041
      (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein
      boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN
      Study #041 had the highest neutralizing antibody activities against the sensitive
      virus along with the highest binding antibody responses, particularly those
      directed toward the V3 loop. DP6-001 sera showed a higher frequency of positive
      neutralizing antibody activities against more resistant viral isolate with a
      significantly higher CD4 binding site (CD4bs) antibody response compared to both
      HVTN studies #041 and #203. No differences were found in CD4-induced (CD4i)
      antibody responses, ADCC activity, or complement activation by Env-specific
      antibody among these sera. Given recent renewed interest in realizing the
      importance of antibody responses for next generation HIV vaccine development,
      different antibody profiles shown in the current report, based on the analysis of
      a wide range of antibody parameters, provide critical biomarker information for
      the selection of HIV vaccines for more advanced human studies and, in particular,
      those that can elicit antibodies targeting conformational-sensitive and
      functionally conserved epitopes.

PMID- 21085487
TI  - Lipocalin-7 is a matricellular regulator of angiogenesis.
AB  - BACKGROUND: Matricellular proteins are extracellular regulators of cellular
      adhesion, signaling and performing a variety of physiological behaviors such as
      proliferation, migration and differentiation. Within vascular microenvironments,
      matricellular proteins exert both positive and negative regulatory cues to
      vascular endothelium. The relative balance of these matricellular cues is
      believed to be critical for vascular homeostasis, angiogenesis activation or
      angiogenesis resolution. However, our knowledge of matricellular proteins within
      vascular microenvironments and the mechanisms by which these proteins impact
      vascular function remain largely undefined. The matricellular protein lipocalin-7
      (LCN7) is found throughout vascular microenvironments, and circumstantial
      evidence suggests that LCN7 may be an important regulator of angiogenesis.
      Therefore, we hypothesized that LCN7 may be an important regulator of vascular
      function. METHODOLOGY AND PRINCIPAL FINDINGS: To test this hypothesis, we
      examined the effect of LCN7 overexpression, recombinant protein and gene
      knockdown in a series of in vitro and in vivo models of angiogenesis. We found
      that overexpression of LCN7 in MB114 and SVEC murine endothelial cell lines or
      administration of highly purified recombinant LCN7 protein increased endothelial
      cell invasion. Similarly, LCN7 increased angiogenic sprouting from quiescent
      endothelial cell monolayers and ex vivo aortic rings. Moreover, LCN7 increased
      endothelial cell sensitivity to TGF-beta but did not affect sensitivity to other
      pro-angiogenic growth factors including bFGF and VEGF. Finally, morpholino based
      knockdown of LCN7 in zebrafish embryos specifically inhibited angiogenic
      sprouting but did not affect vasculogenesis within injected embryos. CONCLUSIONS
      AND SIGNIFICANCE: No functional analysis has previously been performed to
      elucidate the function of LCN7 in vascular or other cellular processes.
      Collectively, our results show for the first time that LCN7 is an important pro
      angiogenic matricellular protein of vascular microenvironments.

PMID- 21085488
TI  - Idiopathic male infertility is strongly associated with aberrant promoter
      methylation of methylenetetrahydrofolate reductase (MTHFR).
AB  - BACKGROUND: Abnormal germline DNA methylation in males has been proposed as a
      possible mechanism compromising spermatogenesis of some men currently diagnosed
      with idiopathic infertility. Previous studies have been focused on imprinted
      genes with DNA methylation in poor quality human sperms. However, recent but
      limited data have revealed that sperm methylation abnormalities may involve large
      numbers of genes or shown that genes that are not imprinted are also affected.
      METHODOLOGY/PRINCIPAL FINDINGS: Using the methylation-specific polymerase chain
      reaction and bisulfite sequencing method, we examined methylation patterns of the
      promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538
      1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal
      fertile controls. Subjects with idiopathic infertility were further divided into
      groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic
      infertile males had MTHFR hypermethylation (both hemimethylation and full
      methylation), compared with 15% of fertile controls (P<0.05). Subjects with
      higher methylation level of MTHFR were more likely to have idiopathic male
      infertility (P-value for trend  = 0.0007). Comparing the two groups of idiopathic
      infertile subjects with different sperm concentrations, a higher methylation
      pattern was found in the group with oligozoospermia. CONCLUSIONS:
      Hypermethylation of the promoter of MTHFR gene in sperms is associated with
      idiopathic male infertility. The functional relevance of hypermathylation of
      MTHFR to male fertility warrants further investigation.

PMID- 21085489
TI  - Applying harmonic optical microscopy for spatial alignment of atrial collagen
      fibers.
AB  - BACKGROUND: Atrial fibrosis creates a vulnerable tissue for atrial fibrillation
      (AF), but the spatial disarray of collagen fibers underlying atrial fibrosis is
      not fully elucidated. OBJECTIVE: This study hypothesizes that harmonics optical
      microscopy can illuminate the spatial mal-alignment of collagen fibers in AF via
      a layer-by-layer approach. PATIENTS AND METHODS: Atrial tissues taken from
      patients who underwent open-heart surgery were examined by harmonics optical
      microscopy. Using the two-dimensional Fourier transformation method, a spectral
      energy description of image texture was constituted and its entropy was used to
      quantify the mal-alignment of collagen fibers. The amount of collagen fiber was
      derived from its area ratio to total atrial tissue in each image. Serum C
      terminal pro-collagen pro-peptide (CICP), pro-matrix metalloproteinase-1 (pro-MMP
      1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were also
      evaluated. RESULTS: 46 patients were evaluated, including 20 with normal sinus
      rhythm and 26 with AF. The entropy of spectral-energy distribution of collagen
      alignment was significantly higher in AF than that in sinus rhythm (3.97 +/- 0.33
      vs. 2.80 +/- 0.18, p<0.005). This difference was more significant in the
      permanent AF group. The amount of collagen was also significantly higher in AF
      patients (0.39 +/- 0.13 vs. 0.18 +/- 0.06, p<0.005) but serum markers of cardiac
      fibrosis were not significantly different between the two groups. CONCLUSIONS:
      Harmonics optical microscopy can quantify the spatial mal-alignment of collagen
      fibers in AF. The entropy of spectral-energy distribution of collagen alignment
      is a potential tool for research in atrial remodeling.

PMID- 21085490
TI  - Protein kinase A binds and activates heat shock factor 1.
AB  - BACKGROUND: Many inducible transcription factors are regulated through batteries
      of posttranslational modifications that couple their activity to inducing
      stimuli. We have studied such regulation of Heat Shock Factor 1 (HSF1), a key
      protein in control of the heat shock response, and a participant in
      carcinogenisis, neurological health and aging. As the mechanisms involved in the
      intracellular regulation of HSF1 in good health and its dysregulation in disease
      are still incomplete we are investigating the role of posttranslational
      modifications in such regulation. METHODOLOGY/PRINCIPAL FINDINGS: In a proteomic
      study of HSF1 binding partners, we have discovered its association with the
      pleiotropic protein kinase A (PKA). HSF1 binds avidly to the catalytic subunit of
      PKA, (PKAcalpha) and becomes phosphorylated on a novel serine phosphorylation
      site within its central regulatory domain (serine 320 or S320), both in vitro and
      in vivo. Intracellular PKAcalpha levels and phosphorylation of HSF1 at S320 were
      both required for HSF1 to be localized to the nucleus, bind to response elements
      in the promoter of an HSF1 target gene (hsp70.1) and activate hsp70.1 after
      stress. Reduction in PKAcalpha levels by small hairpin RNA led to HSF1 exclusion
      from the nucleus, its exodus from the hsp70.1 promoter and decreased hsp70.1
      transcription. Likewise, null mutation of HSF1 at S320 by alanine substitution
      for serine led to an HSF1 species excluded from the nucleus and deficient in
      hsp70.1 activation. CONCLUSIONS: These findings of PKA regulation of HSF1 through
      S320 phosphorylation add to our knowledge of the signaling networks converging on
      this factor and may contribute to elucidating its complex roles in the stress
      response and understanding HSF1 dysregulation in disease.

PMID- 21085491
TI  - Interaction of the retinoblastoma protein with Orc1 and its recruitment to human
      origins of DNA replication.
AB  - BACKGROUND: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle
      progression by binding with E2F transcription factor and repressing the
      expression of a variety of genes required for the G1-S phase transition.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we show that Rb and E2F1 directly
      participate in the control of initiation of DNA replication in human HeLa, U2OS
      and T98G cells by specifically binding to origins of DNA replication in a cell
      cycle regulated manner. We show that, both in vitro and inside the cells, the
      largest subunit of the origin recognition complex (Orc1) specifically binds hypo
      phosphorylated Rb and that this interaction is competitive with the binding of Rb
      to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication
      marks the progression of the G1 phase of the cell cycle toward the G1-S border.
      CONCLUSIONS/SIGNIFICANCE: The participation of Rb and E2F1 in the formation of
      the multiprotein complex that binds origins of DNA replication in mammalian cells
      appears to represent an effective mechanism to couple the expression of genes
      required for cell cycle progression to the activation of DNA replication.

PMID- 21085493
TI  - Fatal cases associated with pandemic influenza A (H1N1) reported in Greece.
AB  - Between 18 May 2009 and 3 May 2010, a total of 149 fatal cases associated with
      pandemic influenza A (H1N1) were reported in Greece. Detailed case-based
      epidemiological information was available for the large majority of fatal cases.
      The time distribution follows an epidemic curve with a peak in the beginning of
      December 2009 and a second peak one month later. This is similar to that of
      laboratory confirmed cases and influenza-like illness cases from our sentinel
      surveillance system, with two weeks delay. The most commonly reported underlying
      conditions were chronic cardiovascular disease and immunosuppression, while the
      most frequently identified risk factor was obesity. These findings should be
      taken into consideration, when vaccination strategies are employed.

PMID- 21085492
TI  - Serum neurotrophin profile in systemic sclerosis.
AB  - BACKGROUND: Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts;
      they can modulate angiogenesis and sympathic vascular function. Thus, they can be
      implicated in the three pathogenic processes of systemic sclerosis (SSc). The
      aims of this study are to determine blood levels of Nerve Growth Factor (NGF),
      Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to
      correlate them with clinical and biological data. METHODS: Serum samples were
      obtained from 55 SSc patients and 32 control subjects to measure NTs levels by
      ELISA and to determine their relationships with SSc profiles. FINDINGS: Serum NGF
      levels were higher in SSc patients (288.26 +/- 170.34 pg/mL) than in control
      subjects (170.34 +/- 50.8 pg/mL, p<0.001) and correlated with gammaglobulins
      levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies
      (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls
      (1121.9 +/- 158.1 vs 1372.9 +/- 190.9 pg/mL, p<0.0001), especially in pulmonary
      arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05).
      NT-3 levels were similar in SSc and in the control group (2657.2 +/- 2296 vs
      2959.3 +/- 2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF
      levels in the SSc group (and not in controls). CONCLUSION: Low BDNF serum levels
      were not previously documented in SSc, particularly in the diffuse SSc subset and
      in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative
      correlation between NGF and BDNF levels observed in SSc and not in healthy
      controls could be implicated in sympathic vascular dysfunction in SSc.

PMID- 21085494
TI  - Generation of novel bone forming cells (monoosteophils) from the cathelicidin
      derived peptide LL-37 treated monocytes.
AB  - BACKGROUND: Bone generation and maintenance involve osteoblasts, osteoclasts, and
      osteocytes which originate from unique precursors and rely on key growth factors
      for differentiation. However, an incomplete understanding of bone forming cells
      during wound healing has led to an unfilled clinical need such as nonunion of
      bone fractures. Since circulating monocytes are often recruited to sites of
      injury and may differentiate into various cell types including osteoclasts, we
      investigated the possibility that circulating monocytes in the context of tissue
      injury may also contribute to bone repair. In particular, we hypothesized that LL
      37 (produced from hCAP-18, cathelicidin), which recruits circulating monocytes
      during injury, may play a role in bone repair. METHODS AND FINDINGS: Treatment of
      monocytes from blood with LL-37 for 6 days resulted in their differentiation to
      large adherent cells. Growth of LL-37-differentiated monocytes on osteologic
      discs reveals bone-like nodule formation by scanning electron microscopy (SEM).
      In vivo transplantation studies in NOD/SCID mice show that LL-37-differentiated
      monocytes form bone-like structures similar to endochondral bone formation.
      Importantly, LL-37-differentiated monocytes are distinct from conventional
      monocyte-derived osteoclasts, macrophages, and dendritic cells and do not express
      markers of the mesenchymal stem cells (MSC) lineage, distinguishing them from the
      conventional precursors of osteoblasts. Furthermore, LL-37 differentiated
      monocytes express intracellular proteins of both the osteoblast and osteoclast
      lineage including osteocalcin (OC), osteonectin (ON), bone sialoprotein II (BSP
      II), osteopontin (OP), RANK, RANKL, MMP-9, tartrate resistant acid phosphatase
      (TRAP), and cathepsin K (CK). CONCLUSION: Blood derived monocytes treated with LL
      37 can be differentiated into a novel bone forming cell that functions both in
      vitro and in vivo. We propose the name monoosteophil to indicate their monocyte
      derived lineage and their bone forming phenotype. These cells may have wide
      ranging implications in the clinic including repair of broken bones and treatment
      of osteoporosis.

PMID- 21085495
TI  - Role of the epigenetic regulator HP1gamma in the control of embryonic stem cell
      properties.
AB  - The unique properties of embryonic stem cells (ESC) rely on long-lasting self
      renewal and their ability to switch in all adult cell type programs. Recent
      advances have shown that regulations at the chromatin level sustain both ESC
      properties along with transcription factors. We have focused our interest on the
      epigenetic modulator HP1gamma (Heterochromatin Protein 1, isoform gamma) that
      binds histones H3 methylated at lysine 9 (meH3K9) and is highly plastic in its
      distribution and association with the transcriptional regulation of specific
      genes during cell fate transitions. These characteristics of HP1gamma make it a
      good candidate to sustain the ESC flexibility required for rapid program changes
      during differentiation. Using RNA interference, we describe the functional role
      of HP1gamma in mouse ESC. The analysis of HP1gamma deprived cells in
      proliferative and in various differentiating conditions was performed combining
      functional assays with molecular approaches (RT-qPCR, microarray). We show that
      HP1gamma deprivation slows down the cell cycle of ESC and decreases their
      resistance to differentiating conditions, rendering the cells poised to
      differentiate. In addition, HP1gamma depletion hampers the differentiation to the
      endoderm as compared with the differentiation to the neurectoderm or the
      mesoderm. Altogether, our results reveal the role of HP1gamma in ESC self-renewal
      and in the balance between the pluripotent and the differentiation programs.

PMID- 21085496
TI  - Insights into the mechanical properties of a silicone oil gel with a 'latent'
      gelator, 1-octadecylamine, and CO(2) as an 'activator'.
AB  - A detailed study of the rheological properties of silicone oil gels, made from a
      low-molecular-mass organic gelator, a combination of 1-octadecylamine (a latent
      gelator) and carbon dioxide (an 'activating' molecule), is reported. Information
      gleaned from the mechanical measurements is used to characterize the gel networks
      and how they respond to temperature and strain. It is shown, for example, that
      very precise measurements of the gel-to-sol transitions can be obtained from
      plots of viscosity versus temperature.

PMID- 21085497
TI  - Expanding the gelation properties of valine-based 3,5-diaminobenzoate
      organogelators with N-alkylurea functionalities.
AB  - A new family of valine-containing 3,5-diaminobenzoate derivatives 2 with N
      alkylurea moieties attached to the valine moieties was prepared. By appending
      these two new N-alkylurea chains to the molecular structure, their organogelating
      properties were extended from only aromatic solvents, to a wide range of other
      types of solvents such as alicyclic hydrocarbons, alcohols and polar solvents
      such as DMSO and DMF. It was also found that a longer N-alkylurea chain conferred
      improved gelation power and higher thermal stability as compared to those of the
      shorter ones.

PMID- 21085498
TI  - A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by
      the annulation of a pyrimidine derivative.
AB  - A new and facile synthesis of 2-thioxoquinazolin-4-ones by introducing a
      benzenoid system in the pyrimidine moiety by reacting ethoxymethylene derivatives
      of 1,3-diarylthiobarbituric acids (DTBA) with active methylene compounds, such as
      malononitrile and ethyl cyanoacetate, in presence of ZnCl2 has been developed.

PMID- 21085499
TI  - Catalysis: transition-state molecular recognition?
AB  - THE KEY TO UNDERSTANDING THE FUNDAMENTAL PROCESSES OF CATALYSIS IS THE TRANSITION
      STATE (TS): indeed, catalysis is a transition-state molecular recognition event.
      Practical objectives, such as the design of TS analogues as potential drugs, or
      the design of synthetic catalysts (including catalytic antibodies), require prior
      knowledge of the TS structure to be mimicked. Examples, both old and new, of
      computational modelling studies are discussed, which illustrate this fundamental
      concept. It is shown that reactant binding is intrinsically inhibitory, and that
      attempts to design catalysts that focus simply upon attractive interactions in a
      binding site may fail. Free-energy changes along the reaction coordinate for
      S(N)2 methyl transfer catalysed by the enzyme catechol-O-methyl transferase are
      described and compared with those for a model reaction in water, as computed by
      hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulations.
      The case is discussed of molecular recognition in a xylanase enzyme that
      stabilises its sugar substrate in a (normally unfavourable) boat conformation and
      in which a single-atom mutation affects the free-energy of activation
      dramatically.

PMID- 21085500
TI  - Physical organic chemistry.

PMID- 21085501
TI  - beta-Hydroxy carbocation intermediates in solvolyses of di- and tetra
      hydronaphthalene substrates.
AB  - Solvolysis of trichloroacetate esters of 2-methoxy-1,2-dihydro-1-naphthols shows
      a remarkably large difference in rates between the cis and trans isomers,
      k(cis)/k(trans) = 1800 in aqueous acetonitrile. This mirrors the behaviour of the
      acid-catalysed dehydration of cis- and trans-naphthalene-1,2-dihydrodiols to form
      2-naphthol, for which k(cis)/k(trans) = 440, but contrasts with that for
      solvolysis of tetrahydronaphthalene substrates, 1-chloro-2-hydroxy-1,2,3,4
      tetrahydronaphthalenes, for which k(cis)/k(trans) = 0.5. Evidence is presented
      showing that the trans isomer of the dihydro substrates reacts unusually slowly
      rather than the cis isomer unusually rapidly. Comparison of rates of solvolysis
      of 1-chloro-1,2,3,4-tetrahydronaphthalene and the corresponding (cis) substrate
      with a 2-hydroxy group indicates that a beta-OH slows the reaction by nearly 2000
      fold, which represents a typical inductive effect characteristic also of cis
      dihydrodiol substrates. The slow reaction of the trans-dihydrodiol substrate is
      consistent with initial formation of a beta-hydroxynaphthalenium carbocation with
      a conformation in which a C-OH occupies an axial position beta to the carbocation
      centre preventing stabilisation of the carbocation by C-H hyperconjugation, which
      would occur in the conformation initially formed from the cis isomer. It is
      suggested that C-H hyperconjugation is particularly pronounced for a beta
      hydroxynaphthalenium ion intermediate because the stability of its no-bond
      resonance structure reflects the presence of an aromatic naphthol structure.

PMID- 21085502
TI  - Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4
      diol rearrangement products of disubstituted 1,3-dithiole derivatives.
AB  - We present a series of compounds by exploiting the unusual 1,4-aryl shift
      observed for electron-rich 1,3-dithiole-2-thione and tetrathiafulvalene (TTF)
      derivatives in the presence of perchloric acid. The mechanistic features of this
      rearrangement are discussed since this synthetic strategy provides an alternative
      route for the synthesis and functionalisation of sulfur rich compounds including
      redox active compounds of TTFs, and a Ni dithiolene.

PMID- 21085503
TI  - Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical
      effects.
AB  - In this work we report on gelation properties, self-assembly motifs, chirality
      effects and morphological characteristics of gels formed by chiral retro
      dipeptidic gelators in the form of terminal diacids (1a-5a) and their dimethyl
      ester (1b-5b) and dicarboxamide (1c-5c) derivatives. Terminal free acid retro
      dipeptides (S,S)-bis(LeuLeu) 1a, (S,S)-bis(PhgPhg) 3a and (S,S)-bis(PhePhe) 5a
      showed moderate to excellent gelation of highly polar water/DMSO and water/DMF
      solvent mixtures. Retro-peptides incorporating different amino acids (S,S)
      (LeuPhg) 2a and (S,S)-(PhgLeu) 4a showed no or very weak gelation. Different
      gelation effectiveness was found for racemic and single enantiomer gelators. The
      heterochiral (S,R)-1c diastereoisomer is capable of immobilizing up to 10 and 4
      times larger volumes of dichloromethane/DMSO and toluene/DMSO solvent mixtures
      compared to homochiral (S,S)-1c. Based on the results of (1)H NMR, FTIR, CD
      investigations, molecular modeling and XRPD studies of diasteroisomeric diesters
      (S,S)-1b/(S,R)-1b and diacids (S,S)-1b/(S,R)-1a, a basic packing model in their
      gel aggregates is proposed. The intermolecular hydrogen bonding between extended
      gelator molecules utilizing both, the oxalamide and peptidic units and layered
      organization were identified as the most likely motifs appearing in the gel
      aggregates. Molecular modeling studies of (S,S)-1a/(S,R)-1a and (S,S)-1b/(S,R)-1b
      diasteroisomeric pairs revealed a decisive stereochemical influence yielding
      distinctly different low energy conformations: those of (S,R)-diastereoisomers
      with lipophilic i-Bu groups and polar carboxylic acid or ester groups located on
      the opposite sides of the oxalamide plane resembling bola amphiphilic structures
      and those of (S,S)-diasteroisomers possessing the same groups located at both
      sides of the oxalamide plane. Such conformational characteristics were found to
      strongly influence both, gelator effectiveness and morphological characteristics
      of gel aggregates.

PMID- 21085504
TI  - Towards racemizable chiral organogelators.
AB  - A chiral organogelator has been synthesized that can be racemized and self
      assembled in apolar solvents whilst at higher concentrations organogels are
      formed. Field emission scanning and transmission electron microscopy revealed the
      formation of bundle fibrils that are able to gelate the solvent. 1H NMR studies
      showed hydrogen-bond interactions between the peptide head groups of neighbouring
      organogelator molecules. The enantiomerically pure organogelator can be racemized
      by the base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) as was evident from chiral
      high-performance liquid chromatography analysis.

PMID- 21085505
TI  - Chain stopper engineering for hydrogen bonded supramolecular polymers.
AB  - Supramolecular polymers are linear chains of low molar mass monomers held
      together by reversible and directional non-covalent interactions, which can form
      gels or highly viscous solutions if the self-assembled chains are sufficiently
      long and rigid. The viscosity of these solutions can be controlled by adding
      monofunctional compounds, which interact with the chain extremities: chain
      stoppers. We have synthesized new substituted ureas and thioureas and tested them
      as chain stoppers for a bis-urea based supramolecular polymer. In particular, the
      bis-thiourea analogue of the bis-urea monomer is shown not to form a
      supramolecular polymer, but a good chain stopper, because it is a strong hydrogen
      bond donor and a weak acceptor. Moreover, all substituted ureas tested reduce the
      viscosity of the supramolecular polymer solutions, but the best chain stopper is
      obtained when two hydrogen bond acceptors are placed in the same relative
      position as for the monomer and when no hydrogen bond donor is present.

PMID- 21085506
TI  - Pyridinium based amphiphilic hydrogelators as potential antibacterial agents.
AB  - The numerous applications of hydrogelators have led to rapid expansion of this
      field. In the present work we report the facile synthesis of amphiphilic
      hydrogelators having a quaternary pyridinium unit coupled to a hydrophobic long
      alkyl chain through an amide bond. Different amphiphiles with various hydrophobic
      chain length and polar head groups were rationally designed and synthesized to
      develop a structure-property relation. A judicious combination of hydrophilic and
      hydrophobic segments led to the development of pyridinium based amphiphilic
      hydrogelators having a minimum gelation concentration of 1.7%, w/v. Field
      emission scanning electronic microscopy (FESEM), atomic force microscopy (AFM),
      photoluminescence, FTIR studies, X-ray diffraction (XRD) and 2D NOESY experiments
      were carried out to elucidate the different non-covalent interactions responsible
      for the self-assembled gelation. The formation of three-dimensional
      supramolecular aggregates originates from the interdigitated bilayer packing of
      the amphiphile leading to the development of an efficient hydrogel.
      Interestingly, the presence of the pyridinium scaffold along with the long alkyl
      chain render these amphiphiles inherently antibacterial. The amphiphilic
      hydrogelators exhibited high antibacterial activity against both Gram-positive
      and Gram-negative bacteria with minimum inhibitory concentration (MIC) values as
      low as 0.4 MUg/mL. Cytotoxicity tests using MTT assay showed 50% NIH3T3 cell
      viability with hydrogelating amphiphile 2 up to 100 MUg/mL.

PMID- 21085507
TI  - Formation of epoxide-amine oligo-adducts as OH-functionalized initiators for the
      ring-opening polymerization of epsilon-caprolactone.
AB  - Epoxide-amine oligo-adducts were synthesized via a one-pot microwave assisted
      heterogeneous catalytic transfer hydrogenation. Accordingly, 4-nitroanisole was
      reduced under microwave conditions to give 4-aminoanisole which reacted
      immediately with the diglycidyl ether of bisphenol A in an addition
      polymerization reaction to yield oligo(amino alcohol)s. The hydroxy groups of the
      new formed oligomers were used as the initiator for the ring-opening
      polymerization of epsilon-caprolactone to produce a graft copolymer.

PMID- 21085508
TI  - alpha,beta-Aziridinylphosphonates by lithium amide-induced phosphonyl migration
      from nitrogen to carbon in terminal aziridines.
AB  - N-Phosphonate terminal aziridines undergo lithium 2,2,6,6-tetramethylpiperidide
      induced N- to C-[1,2]-anionic phosphonyl group migration under experimentally
      straightforward conditions, to provide a stereocontrolled access to synthetically
      valuable trans-alpha,beta-aziridinylphosphonates. The utility of this chemistry
      has been demonstrated in the asymmetric synthesis of a beta-aminophosphonate.

PMID- 21085509
TI  - Differences between beta-Ala and Gly-Gly in the design of amino acids-based
      hydrogels.
AB  - Despite the continuous interest in organogels and hydrogels of low molecular
      weight gelators (LMWG), establishing the relationship between the molecular
      structure and the gelation mechanism is still a challenge. In this paper our
      interest focuses on the consequences of slight molecular modifications on the
      self-assembling behaviour of beta-Ala vs Gly-Gly-based hydrogelators. Previously,
      in our group, amino acid based amphiphiles i.e. Gly-Gly-His-EO2-Alk, a trimodular
      amphiphile (containing three domains: H-bond donor and
      acceptor/hydrophilic/hydrophobic domain, respectively) were reported to act as
      hydrogelators and that the gelation properties were related to hydrogen bonding,
      hydrophobic interactions and pi-pi stacking. Herein, beta-Ala-His-EO2-Alk was
      fully characterised by FT-IR, NMR, SAXS and SEM and the gelation mechanism is
      discussed. It appears that the number of amide groups determines the self
      assembling behaviour into 1D or 2D/3D networks as a result of intimate
      interactions between gelator molecules.

PMID- 21085510
TI  - Preparation and NMR spectra of four isomeric diformyl[2.2]paracyclophanes
      (cyclophanes 66).
AB  - Four isomeric dialdehydes 4, readily available from cycloaddition of propiolic
      aldehyde (2) to 1,2,4,5-hexatetraene (1), were separated by chromatography and
      recrystallization, and were characterized by their spectroscopic data. The
      individual isomers can now be easily identified from their 1H NMR spectra even if
      only one of them is present.

PMID- 21085511
TI  - Synthesis of 3-(quinolin-2-yl)- and 3,6-bis(quinolin-2-yl)-9H-carbazoles.
AB  - A simple and efficient synthesis of novel 3-(quinolin-2-yl)- and 3,6-bis(quinolin
      2-yl)-9H-carbazoles, utilizing sodium ethoxide as a catalyst via a Friedlander
      condensation reaction between 3-acetyl-9-ethyl-9H-carbazole or 3,6-diacetyl-9
      ethyl-9H-carbazole and beta-aminoaldehydes or beta-aminoketones is described. All
      of the title compounds were obtained in good yields of 52-72% and their
      structures were confirmed by IR, 1H NMR, MS, and elemental analysis.

PMID- 21085512
TI  - Donor-acceptor substituted phenylethynyltriphenylenes - excited state
      intramolecular charge transfer, solvatochromic absorption and fluorescence
      emission.
AB  - Several 2-(phenylethynyl)triphenylene derivatives bearing electron donor and
      acceptor substituents on the phenyl rings have been synthesized. The absorption
      and fluorescence emission properties of these molecules have been studied in
      solvents of different polarity. For a given derivative, solvent polarity had
      minimal effect on the absorption maxima. However, for a given solvent the
      absorption maxima red shifted with increasing conjugation of the substituent. The
      fluorescence emission of these derivatives was very sensitive to solvent
      polarity. In the presence of strongly electron withdrawing (-CN) and strongly
      electron donating (-NMe2) substituents large Stokes shifts (up to 130 nm, 7828 cm
      1) were observed in DMSO. In the presence of carbonyl substituents (-COMe and 
      COPh), the largest Stokes shift (140 nm, 8163 cm-1) was observed in ethanol.
      Linear correlation was observed for the Stokes shifts in a Lippert-Mataga plot.
      Linear correlation of Stokes shift was also observed with E(T)(30) scale for
      protic and aprotic solvents but with different slopes. These results indicate
      that the fluorescence emission arises from excited state intramolecular charge
      transfer in these molecules where the triphenylene chromophore acts either as a
      donor or as an acceptor depending upon the nature of the substituent on the
      phenyl ring. HOMO-LUMO energy gaps have been estimated from the electrochemical
      and spectral data for these derivatives. The HOMO and LUMO surfaces were obtained
      from DFT calculations.

PMID- 21085513
TI  - Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in
      propylene carbonate.
AB  - Propylene carbonate can be used as a green solvent for the asymmetric synthesis
      of cyanohydrin trimethylsilyl ethers from aldehydes and trimethylsilyl cyanide
      catalysed by VO(salen)NCS, though reactions are slower in this solvent than the
      corresponding reactions carried out in dichloromethane. A mechanistic study has
      been undertaken, comparing the catalytic activity of VO(salen)NCS in propylene
      carbonate and dichloromethane. Reactions in both solvents obey overall second
      order kinetics, the rate of reaction being dependent on the concentration of both
      the aldehyde and trimethylsilyl cyanide. The order with respect to VO(salen)NCS
      was determined and found to decrease from 1.2 in dichloromethane to 1.0 in
      propylene carbonate, indicating that in propylene carbonate, VO(salen)NCS is
      present only as a mononuclear species, whereas in dichloromethane dinuclear
      species are present which have previously been shown to be responsible for most
      of the catalytic activity. Evidence from 51V NMR spectroscopy suggested that
      propylene carbonate coordinates to VO(salen)NCS, blocking the free coordination
      site, thus inhibiting its Lewis acidity and accounting for the reduction in
      catalytic activity. This explanation was further supported by a Hammett analysis
      study, which indicated that Lewis base catalysis made a much greater contribution
      to the overall catalytic activity of VO(salen)NCS in propylene carbonate than in
      dichloromethane.

PMID- 21085514
TI  - Design and synthesis of a cyclitol-derived scaffold with axial pyridyl appendages
      and its encapsulation of the silver(I) cation.
AB  - Conversion of a myo-inositol derivative into a scyllo-inositol-derived scaffold
      with C3(v) symmetry bearing three axial pyridyl appendages is presented. This pre
      organized hexadentate ligand allows complexation of silver(I). The crystal
      structure of the complex was established.

PMID- 21085515
TI  - Total synthesis of (+/-)-coerulescine and (+/-)-horsfiline.
AB  - Wittig olefination-Claisen rearrangement protocol was applied to obtain 3-allyl
      oxindole. This oxindole was then converted to (+/-)-coerulescine and (+/-)
      horsfiline.

PMID- 21085516
TI  - Evaluation of a digital method to assess evening meal intake in a free-living
      adult population.
AB  - BACKGROUND: In recent years new applications of technologies, including digital
      images, to capture dietary behaviour in real time have been explored. OBJECTIVES:
      To validate a digital method for estimating evening meal intake in a free-living
      adult population, and to examine the feasibility of the method for recording
      evening meal intake over a prolonged period of time. DESIGN: The digital method
      was compared against weighed records of 19 participants' usual evening meals for
      five consecutive days. Two trained image analysts independently estimated the
      weight of individual foods within the meals into major food categories, and the
      nutrient content was calculated. A second study included interviews with 28
      participants recording their evening meals on weekdays for three consecutive
      weeks to get their perspective on the feasibility of the method. RESULTS: High
      correlation coefficients between the digital method and weighed records were
      found for all measured food categories and nutrients. Comparable means and
      acceptable limits of agreement (mean difference +/- 2 SD) were found with regard
      to macronutrient distribution (e.g. fat content -5 to 6 E%), energy density (-75
      to 91 kJ/100 g), and energy-adjusted foods (e.g. fruit and vegetable content -241
      to 236 g/10 MJ). The majority of the participants expressed satisfaction with the
      method and were willing to record their evening meals for 1 month or more using
      the digital method. CONCLUSION: The digital method is valid and feasible for
      evening meal estimation in real-time where a prolonged recording period of
      participants' meals is needed.

PMID- 21085517
TI  - Building capacity for public and population health research in Africa: the
      consortium for advanced research training in Africa (CARTA) model.
AB  - BACKGROUND: Globally, sub-Saharan Africa bears the greatest burden of disease.
      Strengthened research capacity to understand the social determinants of health
      among different African populations is key to addressing the drivers of poor
      health and developing interventions to improve health outcomes and health systems
      in the region. Yet, the continent clearly lacks centers of research excellence
      that can generate a strong evidence base to address the region's socio-economic
      and health problems. OBJECTIVE AND PROGRAM OVERVIEW: We describe the recently
      launched Consortium for Advanced Research Training in Africa (CARTA), which
      brings together a network of nine academic and four research institutions from
      West, East, Central, and Southern Africa, and select northern universities and
      training institutes. CARTA's program of activities comprises two primary,
      interrelated, and mutually reinforcing objectives: to strengthen research
      infrastructure and capacity at African universities; and to support doctoral
      training through the creation of a collaborative doctoral training program in
      population and public health. The ultimate goal of CARTA is to build local
      research capacity to understand the determinants of population health and
      effectively intervene to improve health outcomes and health systems. CONCLUSIONS:
      CARTA's focus on the local production of networked and high-skilled researchers
      committed to working in sub-Saharan Africa, and on the concomitant increase in
      local research and training capacity of African universities and research
      institutes addresses the inability of existing programs to create a critical mass
      of well-trained and networked researchers across the continent. The initiative's
      goal of strengthening human resources and university-wide systems critical to the
      success and sustainability of research productivity in public and population
      health will rejuvenate institutional teaching, research, and administrative
      systems.

PMID- 21085518
TI  - Ratings and rankings.
AB  - In this column, the editor of The Journal of Perinatal Education describes
      ranking systems for scholarly journals. The editor also describes the contents of
      this issue, which offer a broad range of resources, research, and inspiration for
      childbirth educators in their efforts to promote natural, safe, and healthy
      birth.

PMID- 21085519
TI  - Midwifery care: reflections of midwifery clients.
AB  - The purpose of this study was to describe the lived experience of midwifery
      clients throughout the life span. A qualitative study using a phenomenological
      approach was employed. In-depth interviews were conducted with a purposive sample
      of 12 midwifery clients. The research question was: What has been your experience
      with midwifery care? Interviews were audio-recorded and transcribed verbatim.
      Data saturation was achieved and analysis procedures from Colaizzi were used.
      Five themes emerged from the data: 1) decision to seek midwifery care; 2) working
      together in a therapeutic alliance; 3) formulating a birth plan; 4) childbirth
      education; and 5) nurse-midwives as primary health-care providers throughout the
      life span. There is much to learn from listening to the voices of midwifery
      clients.

PMID- 21085520
TI  - New columns in the Annals of Indian Academy of Neurology.

PMID- 21085521
TI  - Angiotensin-converting enzyme inhibitors will help in improving stroke outcome if
      given immediately after stroke.

PMID- 21085522
TI  - Angiotensin-converting enzyme inhibitors will not help in improving stroke
      outcome if given immediately after stroke.

PMID- 21085523
TI  - Use of angiotensin-converting enzyme inhibitors immediately after stroke:
      Commentary.

PMID- 21085524
TI  - Newer insights to the neurological diseases among biblical characters of old
      testament.
AB  - Many people over the years have studied the Bible from a medical point of view
      offering diagnoses for the symptoms and signs that appear to have afflicted
      numerous individuals in the Bible. We review the biblical characters in the Old
      Testament and offer newer insights to their neurological diseases. We first look
      at the battle between Goliath and David. Interestingly, Goliath probably suffered
      from acromegaly. We propose autism as a diagnosis for Samson which would precede
      the first known case of autism by centuries. Isaac was a diabetic, and he
      probably had autonomic neuropathy. Few verses from the books of I Samuel, Psalms,
      and Ezekiel reveal symptoms suggestive of stroke. Jacob suffered from sciatica,
      and the child of the Shunnamite woman in II Kings had a subarachnoid hemorrhage.
      These instances among others found in the Old Testament of the Bible offer newer
      insights on the history of current neurological diseases.

PMID- 21085526
TI  - Child rearing knowledge and practice scales for women with epilepsy.
AB  - BACKGROUND: Comprehensive instruments to evaluate the child rearing knowledge and
      practice are not readily available for clinical research. MATERIALS AND METHODS:
      We have designed in two phases a new instrument to evaluate the child rearing
      knowledge and practice under the four major domains of child rearing. Twenty-five
      subject experts from the field of Paediatrics, Obstetrics, Neurology and Nursing
      elicited the content validity of the instrument. The test retest reliability was
      evaluated by 25 young mothers who completed the CRKS at an interval of two weeks.
      RESULTS: The Content Validity Ratio (CVR) of individual items ranged between 0.6
      to 1. The reliability was tested for the 20 individual items of the CRKS using
      Kappa coefficient. The measurement of agreement Kappa ranged from 0.51 to 1. The
      total knowledge scores and sub scores data were analysed for correlation using
      Pearson's correlation coefficient. A significant Pearson's correlation indicated
      that the total scores were consistent over time (r = 0.89). The sub scores on
      feeding (6 items), Growth and development (4 items), protection (7 items), and
      infant stimulation (3 items) were found to have reliability of 0.91, 0.76, 0.84,
      and 0.89 respectively using Pearson's correlation. CONCLUSION: The instrument is
      found to be valid and reliable and can be used to measure child rearing knowledge
      and practice in early infancy.

PMID- 21085525
TI  - Pattern of neurological admissions in the tropics: Experience at Kano,
      Northwestern Nigeria.
AB  - BACKGROUND: Kano is the most populated state in Nigeria with a population
      totaling 9,383,682. The pattern of neurologic diseases in this area is not known.
      OBJECTIVE: To determine the of pattern of neurologic diseases warranting
      admission in a tertiary hospital in Kano and compare it with those elsewhere in
      the country with the view to using the data generated as a baseline for planning
      purposes and for future studies. MATERIALS AND METHODS: The medical records of
      all cases admitted with neurologic diseases in the Aminu Kano Teaching Hospital,
      Kano between January 2005 and September 2008, were retrospectively reviewed and
      the frequency of neurologic diseases, sex, age, and outcome of these diseases
      analyzed. RESULT: Stroke, predominantly ischemic, accounted for 77.6% of the
      neurological cases for the period of study. Central nervous system infections,
      comprising mainly of meningitis and tetanus, accounted for 6.6% (64) and 3% (29)
      of cases, respectively. The myelopathies were the cause of neurologic admissions
      in 5.4% (53) with paraplegia and quadriplegia resulting from myelopathies
      accounting for 5% (49) and 0.4% (4) of the cases. Hypertensive encephalopathy and
      status epilepticus as the causes of admissions accounted for 1.6% each. Gullain
      Barre syndrome, Parkinson's disease, and cerebral malaria were relatively rare
      causes of neurologic admissions in this study. The average duration of
      hospitalization was 25 days, and regarding outcome, 219 (22.4%) of these cases
      died. CONCLUSIONS: Stroke appeared to be the most common neurologic admission and
      the most common cause of neurologic and medical death in Kano as observed in
      other regions of the country and a little over one-fifths of stroke patients die.
      Central nervous system infections mainly meningitis and tetanus are the next
      common cause of admission. In view of these findings, the provision of a regional
      stroke unit, the improvement of the sanitary conditions of the home and
      environment; the widespread use of immunizations against meningitis, tetanus
      cannot be over-emphasized. These interventions will go a long way to reduce
      morbidity and mortality of stroke and neurologic infections.

PMID- 21085527
TI  - Effect of antihypertensive therapy on cognitive functions of patients with
      hypertension.
AB  - OBJECTIVES: Hypertension is known to be associated with cognitive decline. Many
      studies revealed that control of hypertension with antihypertensive therapy
      controls the cognitive decline associated with hypertension. While there are
      reports that suggest that antihypertensive drugs do not provide protection from
      cognitive decline, the present study is designed to evaluate the cognitive status
      of patients recently diagnosed as hypertensive and effect of 3 month long
      antihypertensive therapy on cognitive functions. MATERIALS AND METHODS: A
      predesigned pretested questionnaire was used to collect the information. The PGI
      memory scale (PGIMS) was employed to assess memory function of patients. Baseline
      memory functions were evaluated before starting the treatment with
      antihypertensive and compared with the cognitive function scores of healthy
      volunteers. After the 3 months of treatment, cognitive functions were evaluated
      again by the same scale. The unpaired t-test was used to compare the cognitive
      functions between case and control and the paired t-test was used to compare pre-
      and post-treatment score. RESULTS: This study revealed that mean scores of six
      subtests of cognitive functions were less in cases as compared to subjects in
      comparison group. After 3 months of antihypertensive therapy, scores of five sub
      tests were found to be increased. Among these five subtests, four were those
      which were found declined at the baseline. CONCLUSION: This suggests that
      antihypertensive therapy given for 3 months improved the score of those cognitive
      function tests in which hypertensive patients perform poorly during recruitment
      and there was no deterioration of any test after 3 months of antihypertensive
      therapy.

PMID- 21085528
TI  - Spontaneous supratentorial intracerebral hemorrhage: Does surgery benefit
      comatose patients?
AB  - INTRODUCTION: Treatment of spontaneous supratentorial intracerebral hemorrhage
      (SICH) is still controversial. We therefore analyzed the comatose patients
      diagnosed as having spontaneous SICH and treated by surgery. MATERIALS AND
      METHODS: We retrospectively analyzed the collected data of 25 comatose patients
      with initial Glasgow Coma Scale (GCS) <= 8 diagnosed as having spontaneous SICH
      and they had been treated by surgical evacuation between 1996 and 2008. The
      outcome was assessed using Glasgow outcome scale (GOS). The side and location of
      the hematoma and ventricular extension of the hematoma were recorded. The
      hematoma volume was graded as mild (<30 cc), moderate (30-60 cc) and massive (>60
      cc). RESULTS: Age of the patients ranged from 25 to 78 years (mean: 59.6 +/-
      15.14 years). Among the 25 patients studied, 11 (44%) were females and 14 (56%)
      were males. GCS before surgery was <5 in 8 (32%) patients and between 5 and 8 in
      17 (68%) patients. The hematoma volume was less than 30 cc in 2 patients, between
      30 and 60 cc in 9 patients and more than 60 cc in 14 patients. Fourteen of the
      patients had no ventricular connection and 11 of the hematomas were connected to
      ventricle. All the 25 patients were treated with craniotomy and evacuation of the
      hematoma was done within an average of 2 hours on admission to the emergency
      department. Postoperatively, no rebleeding occurred in our patients. The most
      important complication was infection in 14 of the patients. The mortality of our
      surgical series was 56%. GCS before surgery was one of the strongest factors
      affecting outcome GCS (oGCS) (P = 0.017). Income GCS (iGCS), however, did not
      affect GOS (P = 0.64). The volume of the hematoma also affected the outcome (P =
      0.037). Ventricular extension of the hematoma did affect the oGCS and GOS (P =
      0.002), but not the iGCS of the patients (P = 0.139). CONCLUSION: Our data
      suggest that being surgically oriented is very important to achieve successful
      outcomes in a select group of patients with SICH.

PMID- 21085529
TI  - Early outcomes after carotid angioplasty with stenting performed by neurologists.
AB  - AIMS: To evaluate the results of carotid artery angioplasty and stenting (CAS) in
      treating extracranial carotid artery stenosis performed by neurologists in our
      center and compare the results with other large published series. MATERIALS AND
      METHODS: Data for all patients who underwent CAS from January 2003 through
      November 2007, was retrieved from the Nanjing Stroke Registry. Perioperative and
      post-procedural complications within 30 days following stenting were analyzed and
      compared with that from other series. A total number of 75 patients were
      enrolled, with a mean age of 65.9 +/- 8.8 years, and 64 (85.3%) of them were
      male. RESULTS: Procedural success was achieved in 74 patients (98.7%). Pre
      treatment stenosis was 73.8 +/- 14.9 and post-treatment residual stenosis was
      less than 10%. Thirty-four patients (45.3%) had bilateral carotid artery disease
      and seven (9.3%) had tandem stenosis. The neurological complication rate was 3.9%
      (one major and two minor strokes). Bradycardia in four (5.3%) and hypotension in
      13 (17.3%) were observed during procedures. Using the Fischer's exact t test, the
      complication rate compared with the large published series did not reveal any
      statistically significant difference (P > 0.05). CONCLUSIONS: We conclude that
      neurologists, with adequate training, can develop and add this technical skill to
      the existing cognitive skill of vascular neurology and safely perform stenting.

PMID- 21085530
TI  - Functional magnetic resonance imaging in primary writing tremor and writer's
      cramp: A pilot study.
AB  - OBJECTIVES: The precise pathophysiology of primary writing tremor (PWT) and
      writer's cramp (WC) is not known. The aim of this study is to compare the
      cerebral activation patterns in patients of PWT, WC and healthy controls, during
      a task of signing on paper, using functional magnetic resonance imaging (fMRI).
      MATERIALS AND METHODS: Six subjects with PWT, three with WC and six healthy
      volunteers were examined using a 1.5-Tesla scanner. The paradigm consisted of
      three times repetition of a set of period of rest and activity. Each set
      consisted of 10 blood oxygen level dependent (BOLD) echo-planar imaging (EPI)
      acquisitions at rest followed by 10 BOLD EPI acquisitions while signing their
      names on paper using the dominant right hand. Entire brain was covered. SPM99
      analysis was done. RESULTS: IN COMPARISON TO THE HEALTHY CONTROLS, THE FOLLOWING
      DIFFERENCES IN CEREBRAL ACTIVATION WERE NOTED IN THE PATIENTS: (a) primary and
      supplementary motor areas showed overactivation in patients of PWT and
      underactivation in patients of WC, (b) the cingulate motor area showed
      underactivation in patients of PWT and overactivation in patients of WC and (c)
      the cerebellar activity was reduced in both WC and PWT. CONCLUSION: Our
      preliminary findings suggest that the cerebral and cerebellar activation patterns
      in PWT and WC during signing on paper are distinct from each other and from
      healthy controls. There may be cerebellar dysfunction in addition to motor
      dysfunctions in the pathogenesis of these disorders.

PMID- 21085532
TI  - Decompression syndrome (Caisson disease) in an Indian diver.
AB  - Acute decompression syndrome (Caisson's disease) is an acute neurological
      emergency in divers. It is caused due to release of nitrogen gas bubbles that
      impinge the blood vessels of the spinal cord and brain and result in severe
      neurodeficit. There are very few case reports in Indian literature. There are
      multiple factors in the pathogenesis of Acute decompression syndrome (Caisson's
      disease) such as health problems in divers (respiratory problems or congenital
      heart diseases like atrial septal defect, patent ductus arteriosus etc), speed of
      ascent from the depth and habits like smoking that render divers susceptible for
      such neurological emergency. Usually, immediate diagnosis of such a condition
      with MRI is not possible in hospitals in the Coastal border. Even though, MRI is
      performed, it has very low specificity and sensitivity. Facilities like
      hyperbaric oxygen treatment are virtually non-existent in these hospitals.
      Therefore, proper education of the divers and appropriate preventive measures in
      professional or recreational divers is recommended.

PMID- 21085531
TI  - Comparison of the configuration of the posterior bifurcation of the posterior
      communicating artery between fetal and adult brains: A study of a Sri Lankan
      population.
AB  - OBJECTIVE: The purpose of this study was to examine the degree of contribution
      from the vertebrobasilar and carotid systems to the origin of the PCA in fetal
      autopsy brains of last trimester of pregnancy and to compare with published data
      on the configuration of adult and fetal brains in a population of Sri Lankan
      origin. MATERIALS AND METHODS: The external diameter of the PcomA, pre
      communicating part (P1), and the post-communicating part (P2) of posterior
      cerebral artery (PCA) of 34 fetal brain in the last trimester of pregnancy (30 to
      40 weeks of gestation) was measured using a stereomicroscope equipped with a
      micrometer calibrator. RESULTS: The blood supply to the occipital lobe mainly via
      the PCA was seen in 25 (59%) of fetal brains as compared to that in the
      literature 220 (93%) in adults brains and the blood supply to the occipital lobe
      mainly via the internal carotid artery (ICA) was seen in 16 (34%) of fetal brains
      as compared to 25 (7%) of adults brains (P < 0.0001), transitional configuration
      where the PcomA is equal in diameter to P1 segment of the PCA was seen in 5
      (7.4%) of fetal brains and 8 (2%) of adults brains. CONCLUSIONS: The present
      study reveals that from the newborn to the adult there is shift from carotid
      system to the vertebrobasilar system, this justifies further studies on different
      racial and geographic regions which may give a clearer picture about the cerebral
      hemodynamics from childhood to adult.

PMID- 21085533
TI  - A study of computed tomography scan and magnetic resonance imaging findings in
      pseudohypoparathyroidism.
AB  - We report three children with pseudohypoparathyroidism aged 13-16 years who
      presented with seizures and tetany. CT scan revealed striatopallidal
      calcification in two. MRI revealed wide-spread involvement showing T1
      hyperintensity in striatopallidodentate distribution in all three and midbrain in
      one patient. T2 and FLAIR images were normal. T1 hyperintensity could represent
      early stage of calcification in whom MRI is more sensitive.

PMID- 21085534
TI  - Dramatic response to infliximab in refractory neurosarcoidosis.
AB  - Sarcoidosis is a systemic disease characterized by noncaseating granulomas in the
      involved organs. Neurologic manifestations involving the central and/or
      peripheral nervous system occur in about 5% of patients. Neurosarcoidosis is
      often refractory to conventional treatment and therefore more effective treatment
      options are needed. While the etiology of the disease is still unknown, there is
      now a better understanding of its pathogenesis on a molecular level. It is clear
      that tumor necrosis factor-alpha (TNFalpha) plays a pivotal role in the
      development of the granulomas and it is believed to be a key cytokine involved in
      the pathogenesis of the disease. Taking advantage of this better understanding of
      disease pathogenesis, anti-TNFalpha agents are being increasingly used to treat
      refractory sarcoidosis. We report a patient with refractory neurosarcoidosis who
      showed dramatic improvement in the clinical and radiological manifestations
      following treatment with infliximab; he suffered a relapse upon discontinuation
      of the medication.

PMID- 21085535
TI  - Opsoclonus-myoclonus syndrome caused by varicella-zoster virus.
AB  - Opsoclonus-myoclonus syndrome (OMS) is a rare condition that has been reported
      from all parts of the world. It is well recognized as a paraneoplastic syndrome
      in children with neuroblastoma and in adults with small-cell carcinoma of lung
      and some other cancers. It may also occur in association with various central
      nervous system infections. We report a case of OMS in a patient with varicella
      zoster virus infection. IgM antibody for varicella-zoster virus was detected in
      the serum and the cerebrospinal fluid. The patient improved after treatment with
      clonazepam and was asymptomatic at 1-month follow-up.

PMID- 21085536
TI  - An elusive diagnosis: Scedosporium apiospermum infection after near-drowning.
AB  - A 51-year-old male was admitted in our institute following an episode of near
      drowning. He later developed ventriculitis and cerebral ring-enhancing lesions.
      He died following a subarachnoid hemorrhage due to rupture of a mycotic aneurysm
      involving the right fetal posterior cerebral artery. Scedosporium apiospermum was
      isolated from the cerebrospinal fluid. Central nervous system invasion by S
      apiospermum may present insidiously in near-drowning patients and, therefore,
      requires a high index of suspicion. In cases with the characteristic cerebral
      ring-enhancing lesions and concomitant ventriculitis, treatment should be
      instituted while awaiting fungal culture. With this article we intend to alert
      neurologists, intensivists, and physicians to this near fatal infection, as early
      identification and prompt treatment with voriconazole may be life saving.

PMID- 21085537
TI  - Cerebral amyloid angiopathy: A clinicopathological study of three cases.
AB  - Cerebral amyloid angiopathy (CAA) is an important cause for intracerebral
      hemorrhage (ICH), yet often goes undiagnosed in the absence of histological
      examination of the blood vessels in the clot. In this study, we report three
      patients who presented with ICH. Two patients had no risk factors for bleed,
      whereas one patient had systemic hypertension. Tissue for analysis was obtained
      during hematoma evacuation in two patients and necropsy in the third.
      Histopathology in all three patients revealed severe degree of amyloid angiopathy
      with extensive amyloid deposits in the vessel walls, which was diagnostic of CAA.
      Both medium- and small-sized leptomeningeal and cortical vessels were affected.
      The vascular amyloid deposits stained with Congo red and displayed characteristic
      birefringence under polarizing light. In addition, vessels also showed fibrinoid
      necrosis and vascular endothelial proliferation. Immunohistochemistry
      demonstrated beta-amyloid peptide in all three cases-the protein most commonly
      involved in sporadic CAA. Senile plaques with amyloid cores were present in all
      areas, whereas neurofibrillary tangles were restricted to the medial temporal
      region in the autopsied case. CAA is an important cause for intracerebral bleed
      and may be a contributory factor even when other risk factors for ICH are
      present. Areas of hemorrhage tend to correlate with severity of CAA changes.

PMID- 21085538
TI  - Acute dengue myositis with rhabdomyolysis and acute renal failure.
AB  - Dengue is an acute mosquito-borne infection caused by dengue viruses from the
      genus flavivirus. Neurologic complications have been attributed chiefly to
      metabolic alterations and to focal and sometimes massive intracranial
      haemorrhages, but anecdotal cases and limited case series have indicated the
      possibility of viral CNS and skeletal muscle invasion causing encephalitis and
      myositis. We present a case of a 40-year-old male who presented with severe
      dengue myositis resulting in quadriparesis, respiratory failure and acute renal
      failure with red urine. His elevated serum creatine kinase (CK), serum and urine
      myoglobin levels justified rhabdomyolysis as the cause of acute renal failure. A
      muscle biopsy revealed inflammatory myositis. He required ventilator support for
      respiratory failure and was treated conservatively. This case highlights the
      severe and persistent muscle involvement in dengue which is a rarity.

PMID- 21085539
TI  - Lobar pattern of microbleeds on susceptibility-weighted magnetic resonance
      imaging.

PMID- 21085541
TI  - Optimizing antiplatelet / antithrombotic therapy.

PMID- 21085540
TI  - A 16-year old male with cortical blindness and focal motor seizures.

PMID- 21085542
TI  - Author's reply.

PMID- 21085543
TI  - Colonoscopy screening in Germany--a success story?

PMID- 21085544
TI  - Eight years of colonoscopic bowel cancer screening in Germany: initial findings
      and projections.
AB  - BACKGROUND: Screening colonoscopy has been offered in Germany since the end of
      2002. Our aim was to estimate numbers of colorectal cancers prevented or detected
      early by screening colonoscopy in 2003-2010. METHODS: Participation rates and
      prevalences of advanced adenomas and colorectal cancers at screening colonoscopy
      in 2003-2008 were obtained from the national screening colonoscopy database by
      age, sex and calendar year. For 2009 and 2010, levels were assumed to remain at
      those observed in 2008. These data were combined in Markov models with population
      figures and estimates of transition rates from advanced adenomas to preclinical
      colorectal cancer and from preclinical cancer to clinically manifest cancer,
      accounting for total mortality. RESULTS: An estimated total number of 98 734
      cases of colorectal cancer at ages 55-84 years are expected to have been
      prevented in Germany by removal of advanced adenomas by the end of 2010. These
      cancers might have become clinically manifest a median time period of 10 years
      after screening colonoscopy. Another 47 168 cases are expected to have been
      detected early at screening colonoscopy, often in a curable stage. CONCLUSION:
      Despite limited participation, the German screening colonoscopy program makes a
      major contribution to prevention and early detection of colorectal cancer.

PMID- 21085545
TI  - The origins of colorectal carcinoma: specific nomenclature for different pathways
      and precursor lesions.
AB  - BACKGROUND: The widespread application of molecular methods in pathology has
      yielded steady advances in our understanding of the origins of colorectal
      carcinoma. Multiple pathways of carcinogenesis have been demonstrated on the
      molecular level and visualized on the histopathological level. The WHO has
      accordingly proposed a number of new designations and terms, particularly for
      precursor lesions, in order to establish a uniform standard for clinical
      diagnosis. These should be put into practice at once. METHODS: In this article,
      we explain the concept of intraepithelial neoplasia, which replaces the older
      concept of dysplasia. Moreover, we use this concept in describing a new mechanism
      of carcinogenesis for colorectal carcinoma, on the basis of a selective review of
      the literature. We estimate the frequency of precursor lesions according to the
      new concept using data from our own patient collective. Finally, we discuss the
      clinical consequences, which have been addressed in the German S3 guideline for
      colorectal carcinoma. RESULTS: The new type of precursor lesion, called "sessile
      serrated adenoma" (SSA), accounts for some 7% of all adenomas in our patient
      collective and is usually found in the right hemicolon. Traditional serrated
      adenomas (TSA) made up 1% to 3% of our cases and were found mainly in the left
      hemicolon and rectum. CONCLUSION: Our observations on the frequency and location
      of serrated adenomas accord with the initial findings published in the
      international literature. In view of the risk that serrated lesions will progress
      more rapidly, it is recommended that they should be completely removed, with
      follow-up at a short interval thereafter (three years according to the German S3
      guidelines).

PMID- 21085547
TI  - Having witnesses present.

PMID- 21085548
TI  - Finding a way home.

PMID- 21085549
TI  - Adolescent bipolar disorder: a clinical vignette.
AB  - Adolescence is a vulnerable developmental phase marked by physical,
      psychological, and social changes that rapidly expose young people to a wide
      range of new stressors. When differentiating between bipolar disorder and teenage
      "acting out," a careful history is important. Adolescent bipolar disorder is a
      psychiatric illness characterized by fluctuating episodes of mood elevation and
      depression that is frequently neither recognized nor formally diagnosed.
      Adolescents with bipolar disorder often manifest a more nonepisodic, chronic
      course with continuous rapid-cycling patterns than do adults. Pharmacologic
      treatment of adolescent bipolar disorder is difficult and often requires
      combination therapy to address comorbidities like attention-deficit/hyperactivity
      disorder and anxiety disorder. Adjuncts to pharmacologic treatment of bipolar
      disorder can be beneficial. Psychosocial treatments include family education,
      enhanced parenting techniques, stress management, and the development of
      effective coping strategies.

PMID- 21085550
TI  - Use of the internet to assist in the treatment of depression and anxiety: a
      systematic review.
AB  - OBJECTIVE: This systematic review aims to describe the Internet's potential role
      in assisting patients with depression and anxiety. DATA SOURCES: A MEDLINE search
      was conducted of articles published between 1998 and 2008 using the terms
      depression and anxiety and Internet, computers and depression and anxiety,
      Internet and compliance and depression, and Internet and adherence and
      depression. STUDY SELECTION: Publications cited include articles concerned with
      the Internet in screening, supporting, educating, and treating patients with
      depression and anxiety. DATA EXTRACTION: The efficacy of Internet-based
      interventions for depression and anxiety was reviewed, alongside the quality of
      available online information regarding these disorders. DATA SYNTHESIS: Little
      progress has been made in developing a universally accepted system for quality
      assurance of medical information Web sites. Furthermore, there is a lack of
      research describing the effect of self-diagnosis sites on meaningful outcomes,
      such as the proportion of patients who go on to receive successful treatment for
      their depression. Early studies of Internet-based cognitive-behavioral therapy
      for depression were promising; however, results of clinical trials for "e
      therapy" have been variable due to methodological issues. A novel compliance
      support Web site for patients with depression and anxiety is being evaluated to
      establish whether providing such assistance can improve patient outcomes.
      CONCLUSIONS: The use of the Internet to assist patients with depression and
      anxiety is currently in its infancy. However, it appears that the Internet has
      great potential to support patients with depression and may consequently also be
      of benefit to physicians.

PMID- 21085551
TI  - A positive association between homeostasis model assessment of insulin resistance
      score and the Trp64Arg polymorphism of the beta3-Adrenergic receptor gene in
      schizophrenia patients in Taiwan.
AB  - OBJECTIVE: To investigate the possible association between the Trp64Arg
      polymorphism of the beta3-adrenergic receptor gene and the homeostasis model
      assessment of insulin resistance (HOMA-IR) index in schizophrenia patients in
      Taiwan. METHOD: A total of 203 inpatients who met DSM-IV diagnostic criteria for
      schizophrenia were recruited from a psychiatry center in Taiwan from September
      2002 to August 2003. All patients had been treated with antipsychotics for at
      least 6 months. The genotyping of the Trp64Arg polymorphism of the beta3
      adrenergic receptor gene was done by the polymerase chain reaction-restriction
      fragment length polymorphism method with the restriction enzyme MvaI. The HOMA-IR
      index was used to indicate the degree of insulin resistance. RESULTS: After
      adjusting for sex, age, and body mass index status, the association between the
      HOMA-IR index and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene
      was still positive (regression coefficient = -0.65, P = .033). CONCLUSIONS: The
      polymorphism of the beta3-adrenergic receptor gene may be related to the
      development of insulin resistance in chronic schizophrenia patients in Taiwan.

PMID- 21085552
TI  - Cognitive-behavioral therapy for chronic cardiopulmonary conditions: preliminary
      outcomes from an open trial.
AB  - OBJECTIVE: To examine the effectiveness of tailored cognitive-behavioral therapy
      (CBT) for veterans with congestive heart failure (CHF) and chronic obstructive
      pulmonary disease (COPD) with comorbid symptoms of depression and/or anxiety.
      METHOD: Twenty-three veterans with CHF and/or COPD, identified from electronic
      medical records at a large Veterans Affairs medical center, with clinically
      significant symptoms of depression (Beck Depression Inventory-II [BDI-II] score
      >= 14) and/or anxiety (State Trait Anxiety Inventory [STAI] score >= 40) were
      enrolled in an open trial from August 2007 to August 2008. All patients received
      CBT delivered mostly by advanced psychology trainees that consisted of 6 weekly
      sessions and 3 telephone booster calls. The intervention expanded traditional CBT
      techniques in order to address patients' emotional and physical health
      difficulties using in-person and telephone-based sessions. Outcomes examined
      depression (BDI-II), anxiety (STAI), and disease-specific quality of life
      (Chronic Respiratory Questionnaire [CRQ] and Kansas City Cardiomyopathy
      Questionnaire [KCCQ]) postintervention and at 3-month follow-up. RESULTS:
      Symptoms of depression (effect size = 0.97) and anxiety (effect size = 0.57) were
      improved at 8 weeks and maintained at 3-month follow-up. Physical disease
      outcomes were also improved for COPD (CRQ mastery effect size = 0.65, CRQ fatigue
      effect size = 0.75) and CHF (KCCQ overall summary score effect size = 1.19).
      CONCLUSIONS: Modifications to traditional CBT approaches have the potential to
      address the emotional and physical health challenges associated with complex
      cardiopulmonary patients. The brief duration and use of telephone-based sessions
      increase the opportunity for CBT interventions to be integrated within primary
      care settings, but additional trials are needed. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00727155.

PMID- 21085554
TI  - History of attempted suicide and reckless driving: a cross-sectional study in
      primary care.
AB  - OBJECTIVE: In this study, we explored whether a past history of suicide attempts
      is associated with a history of reckless driving (ie, driving citations). METHOD:
      Using a cross-sectional design in a consecutive sample of primary care
      outpatients from a suburban setting in Ohio, we surveyed men and women (N = 419),
      aged 18-65 years, who were seeking nonemergent medical care during April 2009.
      With yes/no response options, we queried participants about whether they (1) had
      ever attempted suicide and (2) had tried to hurt or kill themselves. We also
      asked if they had ever been cited for any of 29 driving violations. After the
      elimination of participants who responded illogically to the 2 items exploring
      suicide attempts, the working sample was reduced to 377 participants. RESULTS:
      According to statistical analyses, compared to participants who did not
      acknowledge histories of suicide attempts (n = 337), participants who
      acknowledged histories of suicide attempts (n = 40) were no more likely to report
      a greater number of different types of moving violations or automobile/motorcycle
      accidents (ie, high-risk driving behaviors). However, participants with past
      suicide attempts reported a statistically significantly greater number of
      different types of nonmoving violations (P = .001) as well as being cited for
      leaving the scene of an accident (P = .05), driving while intoxicated (P = .001),
      and having a driver's license revoked (P = .001) than those without past
      attempts. CONCLUSIONS: While a past history of suicide attempts does not appear
      to overtly predict reckless driving behavior, there appear to be other associated
      and specific problematic driving behaviors.

PMID- 21085553
TI  - Metabolic, digestive, and reproductive adverse events associated with antimanic
      treatment in children and adolescents: a retrospective cohort study.
AB  - OBJECTIVE: To identify factors associated with incident metabolic and
      reproductive adverse events in children and adolescents. METHOD: A retrospective
      cohort design evaluating Medicaid medical and pharmacy claims made in South
      Carolina between January 1996 and December 2005 was employed for 3,657 children
      and adolescents (aged 17 years old and younger) prescribed 1 of 3 antimanic
      medications (ie, lithium, carbamazepine, or valproic acid derivatives) and a
      random sample of 4,500 children and adolescents not treated with psychotropic
      medications. RESULTS: Compared to the control sample, the treated cohort was more
      likely to be diagnosed with obesity/weight gain (odds ratio [OR] = 1.89), type 2
      diabetes mellitus (OR = 2.50), dyslipidemia (OR = 1.89), nausea (OR = 1.61),
      anorexia (OR = 3.85), and sexual/reproductive adverse events (OR = 2.04). Within
      the treated cohort, incident dyslipidemia was more likely for those prescribed
      carbamazepine (OR = 1.52) compared to valproate and coprescribed antipsychotics
      (OR = 1.47) or selective serotonin reuptake inhibitors (SSRIs) (OR = 1.49)
      compared to those not taking antipsychotics or taking serotonin-norepinephrine
      reuptake inhibitor/heterocyclic (SNRI/other) antidepressants. The odds of
      developing nausea/vomiting were higher for those prescribed carbamazepine (OR =
      1.70) or lithium (OR = 1.49) compared to valproate, and those coprescribed
      psychostimulants (OR = 1.25) compared to those not taking psychostimulants. The
      odds of developing obesity/weight gain and type 2 diabetes mellitus were higher
      for those coprescribed SSRIs (ORs = 1.72, 2.58) or antipsychotics (ORs = 1.69,
      1.77) compared to those taking SNRI/other antidepressants or not taking
      antipsychotics. Incident sexual/reproductive adverse events were more likely for
      those coprescribed SSRIs (OR = 2.02) compared to those taking SNRI/other
      antidepressants. CONCLUSION: Commonly employed psychotropic agents are associated
      with clinically significant metabolic, digestive, and reproductive-related
      adverse events. Treatment decisions in young populations are usefully informed by
      the somatic consequences of the medication options.

PMID- 21085555
TI  - Patients with treatment-resistant insomnia taking nightly prescription
      medications for sleep: a retrospective assessment of diagnostic and treatment
      variables.
AB  - BACKGROUND: Some chronic insomnia patients who take nightly prescription
      medication achieve less than optimal results. The US Food and Drug Administration
      (FDA) and the American Academy of Sleep Medicine (AASM) recommend reevaluation of
      this type of patient to assess for potential psychiatric or medical causes to
      explain this "failure for insomnia to remit." METHOD: A retrospective chart
      review examined a consecutive series of chronic insomnia patients with persistent
      insomnia complaints despite current nightly use of prescription medication from
      May 2005 to February 2008. To assess the role of psychiatric influences on
      insomnia symptoms, our sample (N = 218) was divided into 2 subgroups: a group
      with a history of psychiatric complaints (psychiatric insomnia, n = 189) and a
      control group of no psychiatric complaints (insomnia, n = 29). RESULTS: The
      average patient reported insomnia for a decade and took prescription medication
      for sleep for a mean of 4.5 years. Although 100% of the sample used nightly sleep
      drugs, only 20% believed medication was the best solution for their condition. As
      evaluated by self-report and polysomnography, these patients exhibited moderately
      severe insomnia across most measures. Only a few differences were noted between
      groups. Subjective perception of insomnia severity was worse in the psychiatric
      insomnia group, which also reported significantly more insomnia-related
      interference in daily functioning, symptoms of sleep maintenance insomnia, and a
      trend toward greater daytime fatigue. The mean Apnea-Hypopnea Index score was
      19.5 events/hour, yielding an obstructive sleep apnea diagnosis in 75% of
      patients per conservative AASM nosology (79% in the insomnia group and 74% in the
      psychiatric insomnia group, P = .22). CONCLUSIONS: In this treatment-seeking
      sample of patients regularly taking sleep medications, residual insomnia was
      widespread, and patients with psychiatric insomnia may have perceived their
      condition as more problematic than a control group of insomnia patients without
      mental health complaints. Both groups exhibited high rates of objectively
      diagnosed obstructive sleep apnea, a medical condition associated with pervasive
      sleep fragmentation. These findings support FDA and AASM guidelines to reassess
      chronic insomnia patients who manifest residual symptoms despite nightly use of
      prescription medication for sleep.

PMID- 21085557
TI  - Complex dynamics in intimate partner violence: a time series study of 16 women.
AB  - OBJECTIVE: Three theories attempt to explain the dynamics of intimate partner
      violence, each representing a different dynamic pattern of violence: periodic,
      chaotic, and random. But few studies assess violence and its potential predictors
      in real time or permit assessment of the dynamics of violence. The purpose of
      this exploratory study was to estimate the degree of complexity in patterns of
      violence and identify predictors of violent events. METHOD: This time series
      study was conducted between September 2006 and April 2007 among 16 adult women
      presenting to a university-affiliated family health center who had experienced
      violence within the past month. Women completed a daily telephone assessment of
      household environment and marital relationship for 2 months. To assess the degree
      of complexity, 3 different measures were used. Lyapunov exponents and saturation
      of correlation dimension were used to approximate dynamic patterns. Vector
      autoregression identified prior-week predictors of violence. Results were pooled
      across the 16 subjects who provided daily reports using meta-analytic techniques.
      RESULTS: Most relationships exhibited complex dynamics, with all 3 distinct
      dynamic patterns found. The longer the relationship had lasted, the more
      predictable and periodic were its dynamics. The more frequent the violence, the
      more complex and sensitive to change were its dynamics. Comparing dynamic
      patterns, 3 distinct combinations of significant prior-day and prior-week
      associations were found. CONCLUSIONS: Although complex dynamics were unrelated to
      duration of violence, there was a dynamic tension between (1) the duration of the
      relationship and its periodic temporal patterns and (2) the frequency of violence
      and its complex dynamics. Identification of dynamic patterns may aid
      understanding of the phenomena of intimate partner violence and lead to novel
      targeted screening, monitoring, and intervention/treatment approaches.

PMID- 21085558
TI  - Added burden of mental disorders on health status among patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) and
      comorbid mental disorders are known to have worse health status. The association
      between these variables remains complex and poorly understood. We sought to
      better understand the association between COPD severity, mental disorders
      (depression/anxiety), and health status. METHOD: This cross-sectional study
      compared participants without COPD or with mild COPD (n = 162) to those with
      moderate (n = 25), severe (n = 38), and very severe (n = 26) COPD. We recruited
      participants from a primary care and a pulmonary clinic at a veterans affairs
      medical center between July 2001 until September 2002. We used the Patient Health
      Questionnaire to screen for depression and anxiety and the Posttraumatic Stress
      Disorder Checklist to screen for posttraumatic stress disorder. Health status was
      assessed with the veteran's version of the Medical Outcomes Study 36-item Short
      Form Health Survey (SF-36) and the Shortness of Breath Questionnaire (SOBQ).
      RESULTS: COPD severity was associated with worse physical status and dyspnea as
      measured by the SF-36 physical component summary and the SOBQ but was not
      associated with worse mental status as measured by the SF-36 mental component
      summary. At each level of COPD severity, participants with mental disorders had
      worse health status and dyspnea as measured by the SF-36 physical component
      summary, mental component summary, and SOBQ. Significant linear trends with COPD
      severity were associated with increased prevalence of any depressive disorder,
      major depressive disorder, and nonpanic/non-PTSD anxiety disorders (all tests for
      linear trend, P < .01). CONCLUSIONS: Independent of COPD severity, comorbid
      mental disorders were associated with worse health status and dyspnea. Studies
      are needed to determine whether patients with comorbid mental disorders may have
      more significant improvement in physical symptoms and functioning if providers
      focus more on psychiatric conditions.

PMID- 21085559
TI  - Akathisia causing secondary severe depression in a cancer patient.

PMID- 21085556
TI  - Accuracy of self-reported weight and height and resulting body mass index among
      obese binge eaters in primary care: relationship with eating disorder and
      associated psychopathology.
AB  - OBJECTIVE: This study assessed the accuracy of self-reported weight, height, and
      body mass index in obese patients with binge-eating disorder (DSM-IV-TR criteria)
      presenting at primary care clinics and tested whether the degree of inaccuracy
      was associated with demographic factors or eating disorder and depressive
      features. METHOD: Sixty-six participants were interviewed using the Eating
      Disorder Examination interview, completed the Eating Disorder Examination
      Questionnaire and the Beck Depression Inventory, and had their height and weight
      measured between November 2007 and May 2009. RESULTS: Self-reported and measured
      weight did not differ significantly, but participants significantly overestimated
      their height (P < .01), and this discrepancy resulted in a significantly lower
      self-reported than measured body mass index (P < .05). Discrepancy scores did not
      differ by eating disorder or depressive symptoms, sex, or ethnicity, although
      increasing age was associated with overestimation of height and underestimation
      of body mass index. CONCLUSIONS: The findings suggest that obese patients with
      binge-eating disorder in primary care settings are reasonably accurate reporters
      of weight and height and that the degree of inaccuracy does not appear to be
      systematically related to eating disorder psychopathology or depressive features.

PMID- 21085560
TI  - A case of lithium-induced symptomatic hypercalcemia.

PMID- 21085561
TI  - Venlafaxine for depression and glossovulvodynia: a case report.

PMID- 21085562
TI  - Childhood trauma and emotional reactivity to hypothetical media events: a pilot
      study.

PMID- 21085563
TI  - A rare case of fatal hyponatremia due to a combination of psychotropic
      polypharmacy and hypothyroidism.

PMID- 21085564
TI  - Severe weight gain with long-acting injectable risperidone: a case report.

PMID- 21085565
TI  - Hyponatremia and central pontine myelinolysis as a result of beer potomania: a
      case report.

PMID- 21085566
TI  - A case of neurotoxic syndrome with the use of long-acting risperidone and
      subsequent olanzapine and paroxetine.

PMID- 21085567
TI  - Qualities of a good psychiatrist: a comparison of opinions between psychiatrists
      and general practitioners.

PMID- 21085568
TI  - Uridine metabolism in HIV-1-infected patients: effect of infection, of
      antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome.
AB  - BACKGROUND: Uridine has been advocated for the treatment of HIV-1/HAART
      associated lipodystrophy (HALS), although its metabolism in HIV-1-infected
      patients is poorly understood. METHODS: Plasma uridine concentrations were
      measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15
      controls and 19 patients. The diagnosis of HALS was performed following the
      criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a
      binary gradient-elution HPLC method. Analysis of genes encoding uridine
      metabolizing enzymes in fat was performed with TaqMan RT-PCR. RESULTS: Median
      plasma uridine concentrations for HIV-1-infected patients were 3.80 umol/l
      (interquartile range: 1.60), and for controls 4.60 umol/l (IQR: 1.8) (P =
      0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein,
      respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma
      uridine level of 4.0 (IC95%: 3.40-4.80) whereas in those with isolated
      lipoatrophy it was 3.25 (2.55-4.15) umol/l/l (P = 0.0066). The expression of
      uridine cytidine kinase and uridine phosphorylase genes was significantly
      decreased in all groups of patients with respect to controls. A higher expression
      of the mRNAs for concentrative nucleoside transporters was found in HIV-1
      infected patients with respect to healthy controls. CONCLUSIONS: HIV-1 infection
      is associated with a decrease in plasma uridine and a shift of uridine to the
      adipose tissue compartment. Antiretroviral therapy was not associated with plasma
      uridine concentrations, but pure lipoatrophic HALS was associated with
      significantly lower plasma uridine concentrations.

PMID- 21085569
TI  - Epidemic levels of drug resistant tuberculosis (MDR and XDR-TB) in a high HIV
      prevalence setting in Khayelitsha, South Africa.
AB  - BACKGROUND: Although multidrug-resistant tuberculosis (MDR-TB) is emerging as a
      significant threat to tuberculosis control in high HIV prevalence countries such
      as South Africa, limited data is available on the burden of drug resistant
      tuberculosis and any association with HIV in such settings. We conducted a
      community-based representative survey to assess the MDR-TB burden in Khayelitsha,
      an urban township in South Africa with high HIV and TB prevalence.
      METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was conducted among
      adult clinic attendees suspected for pulmonary tuberculosis in two large primary
      care clinics, together constituting 50% of the tuberculosis burden in
      Khayelitsha. Drug susceptibility testing (DST) for isoniazid and rifampicin was
      conducted using a line probe assay on positive sputum cultures, and with culture
      based DST for first and second-line drugs. Between May and November 2008, culture
      positive pulmonary tuberculosis was diagnosed in 271 new and 264 previously
      treated tuberculosis suspects (sample enriched with previously treated cases).
      Among those with known HIV status, 55% and 71% were HIV infected respectively.
      MDR-TB was diagnosed in 3.3% and 7.7% of new and previously treated cases. These
      figures equate to an estimated case notification rate for MDR-TB of
      51/100,000/year, with new cases constituting 55% of the estimated MDR-TB burden.
      HIV infection was not significantly associated with rifampicin resistance in
      multivariate analyses. CONCLUSIONS/SIGNIFICANCE: There is an extremely high
      burden of MDR-TB in this setting, most likely representing ongoing transmission.
      These data highlight the need to diagnose drug resistance among all TB cases, and
      for innovative models of case detection and treatment for MDR-TB, in order to
      interrupt transmission and control this emerging epidemic.

PMID- 21085571
TI  - Identifying human kinase-specific protein phosphorylation sites by integrating
      heterogeneous information from various sources.
AB  - Phosphorylation is an important type of protein post-translational modification.
      Identification of possible phosphorylation sites of a protein is important for
      understanding its functions. Unbiased screening for phosphorylation sites by in
      vitro or in vivo experiments is time consuming and expensive; in silico
      prediction can provide functional candidates and help narrow down the
      experimental efforts. Most of the existing prediction algorithms take only the
      polypeptide sequence around the phosphorylation sites into consideration.
      However, protein phosphorylation is a very complex biological process in vivo.
      The polypeptide sequences around the potential sites are not sufficient to
      determine the phosphorylation status of those residues. In the current work, we
      integrated various data sources such as protein functional domains, protein
      subcellular location and protein-protein interactions, along with the polypeptide
      sequences to predict protein phosphorylation sites. The heterogeneous information
      significantly boosted the prediction accuracy for some kinase families. To
      demonstrate potential application of our method, we scanned a set of human
      proteins and predicted putative phosphorylation sites for Cyclin-dependent
      kinases, Casein kinase 2, Glycogen synthase kinase 3, Mitogen-activated protein
      kinases, protein kinase A, and protein kinase C families (available at
      http://cmbi.bjmu.edu.cn/huphospho). The predicted phosphorylation sites can serve
      as candidates for further experimental validation. Our strategy may also be
      applicable for the in silico identification of other post-translational
      modification substrates.

PMID- 21085570
TI  - Genetic evidence implicates the immune system and cholesterol metabolism in the
      aetiology of Alzheimer's disease.
AB  - BACKGROUND: Late Onset Alzheimer's disease (LOAD) is the leading cause of
      dementia. Recent large genome-wide association studies (GWAS) identified the
      first strongly supported LOAD susceptibility genes since the discovery of the
      involvement of APOE in the early 1990s. We have now exploited these GWAS datasets
      to uncover key LOAD pathophysiological processes. METHODOLOGY: We applied a
      recently developed tool for mining GWAS data for biologically meaningful
      information to a LOAD GWAS dataset. The principal findings were then tested in an
      independent GWAS dataset. PRINCIPAL FINDINGS: We found a significant
      overrepresentation of association signals in pathways related to cholesterol
      metabolism and the immune response in both of the two largest genome-wide
      association studies for LOAD. SIGNIFICANCE: Processes related to cholesterol
      metabolism and the innate immune response have previously been implicated by
      pathological and epidemiological studies of Alzheimer's disease, but it has been
      unclear whether those findings reflected primary aetiological events or
      consequences of the disease process. Our independent evidence from two large
      studies now demonstrates that these processes are aetiologically relevant, and
      suggests that they may be suitable targets for novel and existing therapeutic
      approaches.

PMID- 21085572
TI  - Erythropoietin improves the survival of fat tissue after its transplantation in
      nude mice.
AB  - BACKGROUND: Autologous transplanted fat has a high resorption rate, providing a
      clinical challenge for the means to reduce it. Erythropoietin (EPO) has non
      hematopoietic targets, and we hypothesized that EPO may improve long-term fat
      graft survival because it has both pro-angiogenic and anti-apoptotic properties.
      We aimed to determine the effect of EPO on the survival of human fat tissue after
      its transplantation in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: Human fat
      tissue was injected subcutaneously into immunologically-compromised nude mice,
      and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of
      the 15-week study period, the extent of angiogenesis, apoptosis, and histology
      were assessed in the fat grafts. The results were compared to vascular
      endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)
      treated fat grafts. The weight and volume of the EPO-treated grafts were higher
      than those of the PBS-treated grafts, whose weights and volumes were not
      different from those of the VEGF-treated grafts. EPO treatment also increased the
      expression of angiogenic factors and microvascular density, and reduced
      inflammation and apoptosis in a dose-dependent manner in the fat grafts.
      CONCLUSIONS/SIGNIFICANCE: Our data suggest that stimulation of angiogenesis by a
      cluster of angiogenic factors and decreased fat cell apoptosis account for
      potential mechanisms that underlie the improved long-term survival of fat
      transplants following EPO treatment.

PMID- 21085573
TI  - Newcastle disease virus in Madagascar: identification of an original genotype
      possibly deriving from a died out ancestor of genotype IV.
AB  - In Madagascar, Newcastle disease (ND) has become enzootic after the first
      documented epizootics in 1946, with recurrent annual outbreaks causing mortality
      up to 40%. Four ND viruses recently isolated in Madagascar were genotypically and
      pathotypically characterised. By phylogenetic inference based on the F and HN
      genes, and also full-genome sequence analyses, the NDV Malagasy isolates form a
      cluster distant enough to constitute a new genotype hereby proposed as genotype
      XI. This new genotype is presumably deriving from an ancestor close to genotype
      IV introduced in the island probably more than 50 years ago. Our data show also
      that all the previously described neutralising epitopes are conserved between
      Malagasy and vaccine strains. However, the potential implication in vaccination
      failures of specific amino acid substitutions predominantly found on surface
      exposed epitopes of F and HN proteins is discussed.

PMID- 21085574
TI  - MPI-PHYLIP: parallelizing computationally intensive phylogenetic analysis
      routines for the analysis of large protein families.
AB  - BACKGROUND: Phylogenetic study of protein sequences provides unique and valuable
      insights into the molecular and genetic basis of important medical and
      epidemiological problems as well as insights about the origins and development of
      physiological features in present day organisms. Consensus phylogenies based on
      the bootstrap and other resampling methods play a crucial part in analyzing the
      robustness of the trees produced for these analyses. METHODOLOGY: Our focus was
      to increase the number of bootstrap replications that can be performed on large
      protein datasets using the maximum parsimony, distance matrix, and maximum
      likelihood methods. We have modified the PHYLIP package using MPI to enable large
      scale phylogenetic study of protein sequences, using a statistically robust
      number of bootstrapped datasets, to be performed in a moderate amount of time.
      This paper discusses the methodology used to parallelize the PHYLIP programs and
      reports the performance of the parallel PHYLIP programs that are relevant to the
      study of protein evolution on several protein datasets. CONCLUSIONS: Calculations
      that currently take a few days on a state of the art desktop workstation are
      reduced to calculations that can be performed over lunchtime on a modern parallel
      computer. Of the three protein methods tested, the maximum likelihood method
      scales the best, followed by the distance method, and then the maximum parsimony
      method. However, the maximum likelihood method requires significant memory
      resources, which limits its application to more moderately sized protein
      datasets.

PMID- 21085576
TI  - The way to a man's heart is through his stomach: what about horses?
AB  - BACKGROUND: How do we bond to one another? While in some species, like humans,
      physical contact plays a role in the process of attachment, it has been suggested
      that tactile contact's value may greatly differ according to the species
      considered. Nevertheless, grooming is often considered as a pleasurable
      experience for domestic animals, even though scientific data is lacking. On
      another hand, food seems to be involved in the creation of most relationships in
      a variety of species. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the
      horse training context to test the effects of food versus grooming during
      repeated human-horse interactions. The results reveal that food certainly holds a
      key role in the attachment process, while tactile contact was here clearly
      insufficient for bonding to occur. CONCLUSION/SIGNIFICANCE: This study raises
      important questions on the way tactile contact is perceived, and shows that large
      inter-species differences are to be expected.

PMID- 21085575
TI  - The burden and characteristics of enteric fever at a healthcare facility in a
      densely populated area of Kathmandu.
AB  - Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A (S.
      Typhi and S. Paratyphi A) remains a major public health problem in many settings.
      The disease is limited to locations with poor sanitation which facilitates the
      transmission of the infecting organisms. Efficacious and inexpensive vaccines are
      available for S. Typhi, yet are not commonly deployed to control the disease.
      Lack of vaccination is due partly to uncertainty of the disease burden arising
      from a paucity of epidemiological information in key locations. We have collected
      and analyzed data from 3,898 cases of blood culture-confirmed enteric fever from
      Patan Hospital in Lalitpur Sub-Metropolitan City (LSMC), between June 2005 and
      May 2009. Demographic data was available for a subset of these patients (n = 527)
      that were resident in LSMC and who were enrolled in trials. We show a
      considerable burden of enteric fever caused by S. Typhi (2,672; 68.5%) and S.
      Paratyphi A (1,226; 31.5%) at this Hospital over a four year period, which
      correlate with seasonal fluctuations in rainfall. We found that local population
      density was not related to incidence and we identified a focus of infections in
      the east of LSMC. With data from patients resident in LSMC we found that the
      median age of those with S. Typhi (16 years) was significantly less than S.
      Paratyphi A (20 years) and that males aged 15 to 25 were disproportionately
      infected. Our findings provide a snapshot into the epidemiological patterns of
      enteric fever in Kathmandu. The uneven distribution of enteric fever patients
      within the population suggests local variation in risk factors, such as
      contaminated drinking water. These findings are important for initiating a
      vaccination scheme and improvements in sanitation. We suggest any such
      intervention should be implemented throughout the LSMC area.

PMID- 21085577
TI  - BMI, all-cause and cause-specific mortality in Chinese Singaporean men and women:
      the Singapore Chinese health study.
AB  - BACKGROUND: The optimal range of relative weight for morbidity and mortality in
      Asian populations is an important question in need of more thorough
      investigation, especially as obesity rates increase. We aimed to examine the
      association between body mass index (BMI), all cause and cause-specific mortality
      to determine the optimal range of BMI in relation to mortality in Chinese men and
      women in Singapore. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from a
      prospective cohort study of 51,251 middle-aged or older (45-74) Chinese men and
      women in the Singapore Chinese Health Study. Participants were enrolled and data
      on body weight and covariates were collected in 1993-1998 and participants were
      followed through 2008. The analysis accounted for potential methodological issues
      through stratification on smoking and age, thorough adjustment of demographic and
      lifestyle confounders and exclusion of deaths early in the follow-up.
      CONCLUSIONS/SIGNIFICANCE: Increased risk of mortality was apparent in underweight
      (<18.5) and obese BMI categories (>=27.5) independent of age and smoking.
      Regardless of age or BMI, smoking considerably increased the rate of mortality
      and modified the association between BMI and mortality. The most favorable range
      of BMI for mortality rates and risk in non-smoking persons below age 65 was 18.5
      21.4 kg/m(2), and for non-smoking persons aged 65 and above was 21.5-24.4
      kg/m(2).

PMID- 21085578
TI  - Temporal pattern of ICAM-I mediated regulatory T cell recruitment to sites of
      inflammation in adoptive transfer model of multiple sclerosis.
AB  - Migration of immune cells to the target organ plays a key role in autoimmune
      disorders like multiple sclerosis (MS). However, the exact underlying mechanisms
      of this active process during autoimmune lesion pathogenesis remain elusive. To
      test if pro-inflammatory and regulatory T cells migrate via a similar molecular
      mechanism, we analyzed the expression of different adhesion molecules, as well as
      the composition of infiltrating T cells in an in vivo model of MS, adoptive
      transfer experimental autoimmune encephalomyelitis in rats. We found that the
      upregulation of ICAM-I and VCAM-I parallels the development of clinical disease
      onset, but persists on elevated levels also in the phase of clinical remission.
      However, the composition of infiltrating T cells found in the developing versus
      resolving lesion phase changed over time, containing increased numbers of
      regulatory T cells (FoxP3) only in the phase of clinical remission. In order to
      test the relevance of the expression of cell adhesion molecules, animals were
      treated with purified antibodies to ICAM-I and VCAM-I either in the phase of
      active disease or in early remission. Treatment with a blocking ICAM-I antibody
      in the phase of disease progression led to a milder disease course. However,
      administration during early clinical remission aggravates clinical symptoms.
      Treatment with anti-VCAM-I at different timepoints had no significant effect on
      the disease course. In summary, our results indicate that adhesion molecules are
      not only important for capture and migration of pro-inflammatory T cells into the
      central nervous system, but also permit access of anti-inflammatory cells, such
      as regulatory T cells. Therefore it is likely to assume that intervention at the
      blood brain barrier is time dependent and could result in different therapeutic
      outcomes depending on the phase of CNS lesion development.

PMID- 21085579
TI  - Re-evaluation of Sinocastor (Rodentia: Castoridae) with implications on the
      origin of modern beavers.
AB  - The extant beaver, Castor, has played an important role shaping landscapes and
      ecosystems in Eurasia and North America, yet the origins and early evolution of
      this lineage remain poorly understood. Here we use a geometric morphometric
      approach to help re-evaluate the phylogenetic affinities of a fossil skull from
      the Late Miocene of China. This specimen was originally considered Sinocastor,
      and later transferred to Castor. The aim of this study was to determine whether
      this form is an early member of Castor, or if it represents a lineage outside of
      Castor. The specimen was compared to 38 specimens of modern Castor (both C.
      canadensis and C. fiber) as well as fossil specimens of C. fiber (Pleistocene),
      C. californicus (Pliocene) and the early castorids Steneofiber eseri (early
      Miocene). The results show that the specimen falls outside the Castor morphospace
      and that compared to Castor, Sinocastor possesses a: 1) narrower post-orbital
      constriction, 2) anteroposteriorly shortened basioccipital depression, 3)
      shortened incisive foramen, 4) more posteriorly located palatine foramen, 5)
      longer rostrum, and 6) longer braincase. Also the specimen shows a much shallower
      basiocciptal depression than what is seen in living Castor, as well as
      prominently rooted molars. We conclude that Sinocastor is a valid genus. Given
      the prevalence of apparently primitive traits, Sinocastor might be a near
      relative of the lineage that gave rise to Castor, implying a possible Asiatic
      origin for Castor.

PMID- 21085580
TI  - APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP
      fragments in human and rat neuronal cells.
AB  - Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes
      simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During
      these episodes, newly produced virions may also reach the central nervous system
      (CNS), causing productive but generally asymptomatic infections. Epidemiological
      and experimental findings suggest that HSV-1 might contribute to the pathogenesis
      of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is
      related to an overproduction of amyloid beta (Abeta) and other neurotoxic
      peptides, which occurs during amyloidogenic endoproteolytic processing of the
      transmembrane amyloid precursor protein (APP). The aim of our study was to
      identify the effects of productive HSV-1 infection on APP processing in neuronal
      cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat
      cortical neurons is followed by multiple cleavages of APP, which result in the
      intra- and/or extra-cellular accumulation of various neurotoxic species. These
      include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that
      comprise portions of Abeta; ii) N-terminal APP-Fs that are secreted; iii)
      intracellular C-terminal APP-Fs; and iv) Abeta(1-40) and Abeta(1-42). Western
      blot analysis of infected-cell lysates treated with formic acid suggests that APP
      F35 may be an Abeta oligomer. The multiple cleavages of APP that occur in
      infected cells are produced in part by known components of the amyloidogenic APP
      processing pathway, i.e., host-cell beta-secretase, gamma-secretase, and caspase
      3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells
      can generate multiple APP fragments with well-documented neurotoxic potentials.
      It is tempting to speculate that intra- and extracellular accumulation of these
      species in the CNS resulting from repeated HSV-1 reactivation could, in the
      presence of other risk factors, play a co-factorial role in the development of
      AD.

PMID- 21085581
TI  - Early-age-related changes in proteostasis augment immunopathogenesis of sepsis
      and acute lung injury.
AB  - BACKGROUND: The decline of proteasomal activity is known to be associated with
      the age-related disorders but the early events involved in this process are not
      apparent. To address this, we investigated the early-age-related (pediatric vs.
      adult) mechanisms that augment immunopathogenesis of sepsis and acute lung
      injury. METHODOLOGY/PRINCIPAL FINDINGS: The 3-weeks (pediatric) and 6-months
      (adult) old C57BL/6 mice were selected as the study groups. Mice were subjected
      to 1*20 cecal ligation and puncture (CLP) mediated sepsis or intratracheal
      Psuedomonas aeruginosa (Pa)-LPS induced acute lung injury (ALI).We observed a
      significant increase in basal levels of pro-inflammatory cytokine, IL-6 and
      neutrophil activity marker, myeloperoxidase (MPO) in the adult mice compared to
      the pediatric indicating the age-related constitutive increase in inflammatory
      response. Next, we found that age-related decrease in PSMB6 (proteasomal subunit)
      expression in adult mice results in accumulation of ubiquitinated proteins that
      triggers the unfolded protein response (UPR). We identified that Pa-LPS induced
      activation of UPR modifier, p97/VCP (valosin-containing protein) in the adult
      mice lungs correlates with increase in Pa-LPS induced NFkappaB levels. Moreover,
      we observed a constitutive increase in p-eIF2alpha indicating a protective ER
      stress response to accumulation of ubiquitinated-proteins. We used MG-132
      treatment of HBE cells as an in vitro model to standardize the efficacy of
      salubrinal (inhibitor of eIF2alpha de-phosphorylation) in controlling the
      accumulation of ubiquitinated proteins and the NFkappaB levels. Finally, we
      evaluated the therapeutic efficacy of salubrinal to correct proteostasis
      imbalance in the adult mice based on its ability to control CLP induced IL-6
      secretion or recruitment of pro-inflammatory cells. CONCLUSIONS/SIGNIFICANCE: Our
      data demonstrate the critical role of early-age-related proteostasis-imbalance as
      a novel mechanism that augments the NFkappaB mediated inflammation in sepsis and
      ALI. Moreover, our data suggest the therapeutic efficacy of salubrinal in
      restraining NFkappaB mediated inflammation in the adult or older subjects.

PMID- 21085583
TI  - Extensive co-operation between the Epstein-Barr virus EBNA3 proteins in the
      manipulation of host gene expression and epigenetic chromatin modification.
AB  - Epstein-Barr virus (EBV) is able to drive the transformation of B-cells,
      resulting in the generation of lymphoblastoid cell lines (LCLs) in vitro. EBV
      nuclear proteins EBNA3A and EBNA3C are necessary for efficient transformation,
      while EBNA3B is dispensable. We describe a transcriptome analysis of BL31 cells
      infected with a series of EBNA3-knockout EBVs, including one deleted for all
      three EBNA3 genes. Using Affymetrix Exon 1.0 ST microarrays analysed with the
      MMBGX algorithm, we have identified over 1000 genes whose regulation by EBV
      requires one of the EBNA3s. Remarkably, a third of the genes identified require
      more than one EBNA3 for their regulation, predominantly EBNA3C co-operating with
      either EBNA3B, EBNA3A or both. The microarray was validated by real-time PCR,
      while ChIP analysis of a selection of co-operatively repressed promoters
      indicates a role for polycomb group complexes. Targets include genes involved in
      apoptosis, cell migration and B-cell differentiation, and show a highly
      significant but subtle alteration in genes involved in mitosis. In order to
      assess the relevance of the BL31 system to LCLs, we analysed the transcriptome of
      a set of EBNA3B knockout (3BKO) LCLs. Around a third of the genes whose
      expression level in LCLs was altered in the absence of EBNA3B were also altered
      in 3BKO-BL31 cell lines.Among these are TERT and TCL1A, implying that EBV-induced
      changes in the expression of these genes are not required for B-cell
      transformation. We also identify 26 genes that require both EBNA3A and EBNA3B for
      their regulation in LCLs. Together, this shows the complexity of the interaction
      between EBV and its host, whereby multiple EBNA3 proteins co-operate to modulate
      the behaviour of the host cell.

PMID- 21085584
TI  - Morphometrics as an insight into processes beyond tooth shape variation in a bank
      vole population.
AB  - Phenotype variation is a key feature in evolution, being produced by development
      and the target of the screening by selection. We focus here on a variable
      morphological feature: the third upper molar (UM3) of the bank vole, aiming at
      identifying the sources of this variation. Size and shape of the UM3 occlusal
      surface was quantified in successive samples of a bank vole population. The first
      source of variation was the season of trapping, due to differences in the age
      structure of the population in turn affecting the wear of the teeth. The second
      direction of variation corresponded to the occurrence, or not, of an additional
      triangle on the tooth. This intra-specific variation was attributed to the space
      available at the posterior end of the UM3, allowing or not the addition of a
      further triangle.This size variation triggering the shape polymorphism is not
      controlled by the developmental cascade along the molar row. This suggests that
      other sources of size variation, possibly epigenetic, might be involved. They
      would trigger an important shape variation as side-effect by affecting the
      termination of the sequential addition of triangles on the tooth.

PMID- 21085585
TI  - Genome-wide analysis of copy number variation in type 1 diabetes.
AB  - Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a
      genetic component predisposing to disease. However, a recent large-scale genome
      wide association study concluded that identified genetic factors, single
      nucleotide polymorphisms, do not account for overall familiality. Another class
      of genetic variation is the amplification or deletion of >1 kilobase segments of
      the genome, also termed copy number variations (CNVs). We performed genome-wide
      CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl)
      cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the
      Birdsuite copy number calling software. We identified 39 CNVs as enriched or
      depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group
      of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were
      also respectively enriched or depleted in the Twin cohort, suggesting that these
      variants may be involved in the development of islet autoimmunity, as the
      presently unaffected twin is at high risk for developing islet autoimmunity and
      T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21,
      near an HLA-DQ allele. CNVs were found that were both enriched or depleted in
      patients with or at high risk for developing T1D. These regions may represent
      genetic variants contributing to development of islet autoimmunity in T1D.

PMID- 21085586
TI  - Analysis of mice lacking DNaseI hypersensitive sites at the 5' end of the IgH
      locus.
AB  - The 5' end of the IgH locus contains a cluster of DNaseI hypersensitive sites,
      one of which (HS1) was shown to be pro-B cell specific and to contain binding
      sites for the transcription factors PU.1, E2A, and Pax5. These data as well as
      the location of the hypersensitive sites at the 5' border of the IgH locus
      suggested a possible regulatory function for these elements with respect to the
      IgH locus. To test this notion, we generated mice carrying targeted deletions of
      either the pro-B cell specific site HS1 or the whole cluster of DNaseI
      hypersensitive sites. Lymphocytes carrying these deletions appear to undergo
      normal development, and mutant B cells do not exhibit any obvious defects in
      V(D)J recombination, allelic exclusion, or class switch recombination. We
      conclude that deletion of these DNaseI hypersensitive sites does not have an
      obvious impact on the IgH locus or B cell development.

PMID- 21085587
TI  - The cerebellar nodulus/uvula integrates otolith signals for the translational
      vestibulo-ocular reflex.
AB  - BACKGROUND: The otolith-driven translational vestibulo-ocular reflex (tVOR)
      generates compensatory eye movements to linear head accelerations. Studies in
      humans indicate that the cerebellum plays a critical role in the neural control
      of the tVOR, but little is known about mechanisms of this control or the
      functions of specific cerebellar structures. Here, we chose to investigate the
      contribution of the nodulus and uvula, which have been shown by prior studies to
      be involved in the processing of otolith signals in other contexts.
      METHODOLOGY/PRINCIPAL FINDINGS: We recorded eye movements in two rhesus monkeys
      during steps of linear motion along the interaural axis before and after surgical
      lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye
      velocity during constant-velocity motion but had only a small effect on the
      response to initial head acceleration. We fit eye velocity to a linear
      combination of head acceleration and velocity and to a dynamic mathematical model
      of the tVOR that incorporated a specific integrator of head acceleration. Based
      on parameter optimization, the lesion decreased the gain of the pathway
      containing this new integrator by 62%. The component of eye velocity that
      depended directly on head acceleration changed little (gain decrease of 13%). In
      a final set of simulations, we compared our data to the predictions of previous
      models of the tVOR, none of which could account for our experimental findings.
      CONCLUSIONS/ SIGNIFICANCE: Our results provide new and important information
      regarding the neural control of the tVOR. Specifically, they point to a key role
      for the cerebellar nodulus and uvula in the mathematical integration of afferent
      linear head acceleration signals. This function is likely to be critical not only
      for the tVOR but also for the otolith-mediated reflexes that control posture and
      balance.

PMID- 21085582
TI  - Environmental barcoding reveals massive dinoflagellate diversity in marine
      environments.
AB  - BACKGROUND: Dinoflagellates are an ecologically important group of protists with
      important functions as primary producers, coral symbionts and in toxic red tides.
      Although widely studied, the natural diversity of dinoflagellates is not well
      known. DNA barcoding has been utilized successfully for many protist groups. We
      used this approach to systematically sample known "species", as a reference to
      measure the natural diversity in three marine environments. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we assembled a large cytochrome c oxidase 1 (COI)
      barcode database from 8 public algal culture collections plus 3 private
      collections worldwide resulting in 336 individual barcodes linked to specific
      cultures. We demonstrate that COI can identify to the species level in 15
      dinoflagellate genera, generally in agreement with existing species names.
      Exceptions were found in species belonging to genera that were generally already
      known to be taxonomically challenging, such as Alexandrium or Symbiodinium. Using
      this barcode database as a baseline for cultured dinoflagellate diversity, we
      investigated the natural diversity in three diverse marine environments
      (Northeast Pacific, Northwest Atlantic, and Caribbean), including an evaluation
      of single-cell barcoding to identify uncultivated groups. From all three
      environments, the great majority of barcodes were not represented by any known
      cultured dinoflagellate, and we also observed an explosion in the diversity of
      genera that previously contained a modest number of known species, belonging to
      Kareniaceae. In total, 91.5% of non-identical environmental barcodes represent
      distinct species, but only 51 out of 603 unique environmental barcodes could be
      linked to cultured species using a conservative cut-off based on distances
      between cultured species. CONCLUSIONS/SIGNIFICANCE: COI barcoding was successful
      in identifying species from 70% of cultured genera. When applied to environmental
      samples, it revealed a massive amount of natural diversity in dinoflagellates.
      This highlights the extent to which we underestimate microbial diversity in the
      environment.

PMID- 21085588
TI  - Short-term environmental enrichment enhances adult neurogenesis, vascular network
      and dendritic complexity in the hippocampus of type 1 diabetic mice.
AB  - BACKGROUND: Several brain disturbances have been described in association to type
      1 diabetes in humans. In animal models, hippocampal pathological changes were
      reported together with cognitive deficits. The exposure to a variety of
      environmental stimuli during a certain period of time is able to prevent brain
      alterations and to improve learning and memory in conditions like stress, aging
      and neurodegenerative processes. METHODOLOGY/PRINCIPAL FINDINGS: We explored the
      modulation of hippocampal alterations in streptozotocin-induced type 1 diabetic
      mice by environmental enrichment. In diabetic mice housed in standard conditions
      we found a reduction of adult neurogenesis in the dentate gyrus, decreased
      dendritic complexity in CA1 neurons and a smaller vascular fractional area in the
      dentate gyrus, compared with control animals in the same housing condition. A
      short exposure -10 days- to an enriched environment was able to enhance
      proliferation, survival and dendritic arborization of newborn neurons, to recover
      dendritic tree length and spine density of pyramidal CA1 neurons and to increase
      the vascular network of the dentate gyrus in diabetic animals.
      CONCLUSIONS/SIGNIFICANCE: The environmental complexity seems to constitute a
      strong stimulator competent to rescue the diabetic brain from neurodegenerative
      progression.

PMID- 21085589
TI  - Mycobacterium tuberculosis phosphoribosylpyrophosphate synthetase: biochemical
      features of a crucial enzyme for mycobacterial cell wall biosynthesis.
AB  - The selection and soaring spread of Mycobacterium tuberculosis multidrug
      resistant (MDR-TB) and extensively drug-resistant strains (XDR-TB) is a severe
      public health problem. Currently, there is an urgent need for new drugs for
      tuberculosis treatment, with novel mechanisms of action and, moreover, the
      necessity to identify new drug targets. Mycobacterial phosphoribosylpyrophosphate
      synthetase (MtbPRPPase) is a crucial enzyme involved in the biosynthesis of
      decaprenylphosphoryl-arabinose, an essential precursor for the mycobacterial cell
      wall biosynthesis. Moreover, phosphoribosylpyrophosphate, which is the product of
      the PRPPase catalyzed reaction, is the precursor for the biosynthesis of
      nucleotides and of some amino acids such as histidine and tryptophan. In this
      context, the elucidation of the molecular and functional features of MtbPRPPase
      is mandatory. MtbPRPPase was obtained as a recombinant form, purified to
      homogeneity and characterized. According to its hexameric form, substrate
      specificity and requirement of phosphate for activity, the enzyme proved to
      belong to the class I of PRPPases. Although the sulfate mimicked the phosphate,
      it was less effective and required higher concentrations for the enzyme
      activation. MtbPRPPase showed hyperbolic response to ribose 5-phosphate, but
      sigmoidal behaviour towards Mg-ATP. The enzyme resulted to be allosterically
      activated by Mg(2+) or Mn(2+) and inhibited by Ca(2+) and Cu(2+) but, differently
      from other characterized PRPPases, it showed a better affinity for the Mn(2+) and
      Cu(2+) ions, indicating a different cation binding site geometry. Moreover, the
      enzyme from M. tuberculosis was allosterically inhibited by ADP, but less
      sensitive to inhibition by GDP. The characterization of M. tuberculosis PRPPase
      provides the starting point for the development of inhibitors for antitubercular
      drug design.

PMID- 21085590
TI  - The impact of coping style on gaze duration.
AB  - The understanding of individual differences in response to threat (e.g.,
      attentional bias) is important to better understand the development of anxiety
      disorders. Previous studies revealed only a small attentional bias in high
      anxious (HA) subjects. One explanation for this finding may be the assumption
      that all HA-subjects show a constant attentional bias. Current models distinguish
      HA-subjects depending on their level of tolerance for uncertainty and for
      arousal. These models assume that only HA-subjects with intolerance for
      uncertainty but tolerance for arousal ("sensitizers") show an attentional bias,
      compared to HA-subjects with intolerance for uncertainty and intolerance for
      arousal ("fluctuating subjects"). Further, it is assumed that repressors (defined
      as intolerance for arousal but tolerance for uncertainty) would react with
      avoidance behavior when confronted with threatening stimuli. The present study
      investigated the influence of coping styles on attentional bias. After an
      extensive recruiting phase, 36 subjects were classified into three groups
      (sensitizers, fluctuating, and repressors). All subjects were exposed to
      presentations of happy and threatening faces, while recording gaze durations with
      an eye-tracker. The results showed that only sensitizer showed an attentional
      bias: they gazed longer at the threatening face rather than at the happy face
      during the first 500 ms. The results support the findings of the relationship
      between anxiety and attention and extend these by showing variations according to
      coping styles. The differentiation of subjects according to a multifaceted coping
      style allows a better prediction of the attentional bias and contributes to an
      insight into the complex interplay of personality, coping, and behavior.

PMID- 21085591
TI  - Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic,
      recombinant modified vaccinia Ankara-HIV-1 vaccine candidate.
AB  - BACKGROUND: We conducted a Phase I randomized, dose-escalation, route-comparison
      trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified
      vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV
      sequences were derived from circulating recombinant form CRF01_AE, which
      predominates in Thailand. The objective was to evaluate safety and immunogenicity
      of MVA-CMDR in human volunteers in the US and Thailand. METHODOLOGY/PRINCIPAL
      FINDINGS: MVA-CMDR or placebo was administered intra-muscularly (IM; 10(7) or
      10(8) pfu) or intradermally (ID; 10(6) or 10(7) pfu) at months 0, 1 and 3, to 48
      healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each
      dosage group were randomized to receive MVA-CMDR or placebo (10?2). Volunteers
      were actively monitored for local and systemic reactogenicity and adverse events
      post vaccination. Cellular immunogenicity was assessed by a validated IFNgamma
      Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation
      and a (51)Cr-release assay. Humoral immunogenicity was assessed by ADCC for gp120
      and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well
      tolerated with no vaccine related serious adverse events. Cell-mediated immune
      responses were: (i) moderate in magnitude (median IFNgamma Elispot of 78
      SFC/10(6) PBMC at 10(8) pfu IM), but high in response rate (70% (51)Cr-release
      positive; 90% Elispot positive; 100% ICS positive, at 10(8) pfu IM); (ii)
      predominantly HIV Env-specific CD4(+) T cells, with a high proliferative capacity
      and durable for at least 6 months (100% LPA response rate by the IM route); (iv)
      dose- and route-dependent with 10(8) pfu IM being the most immunogenic treatment.
      Binding antibodies against gp120 and p24 were detectable in all vaccination
      groups with ADCC capacity detectable at the highest dose (40% positive at 10(8)
      pfu IM). CONCLUSIONS/SIGNIFICANCE: MVA-CMDR delivered both intramuscularly and
      intradermally was safe, well-tolerated and elicited durable cell-mediated and
      humoral immune responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00376090.

PMID- 21085592
TI  - Receiving post-conflict affiliation from the enemy's friend reconciles former
      opponents.
AB  - The adaptive function of bystander initiated post-conflict affiliation (also:
      consolation & appeasement) has been debated for 30 years. Three influential
      hypotheses compete for the most likely explanation but have not previously been
      tested with a single data set. The consolation hypothesis argues that bystander
      affiliation calms the victim and reduces their stress levels. The self-protection
      hypothesis proposes that a bystander offers affiliation to either opponent to
      protect himself from redirected aggression by this individual. The relationship
      repair hypothesis suggests a bystander can substitute for a friend to reconcile
      the friend with the friend's former opponent. Here, we contrast all three
      hypotheses and tested their predictions with data on wild chimpanzees (Pan
      troglodytes verus) of the Tai National Park, Cote d'Ivoire. We examined the first
      and second post-conflict interactions with respect to both the dyadic and triadic
      relationships between the bystander and the two opponents. Results showed that
      female bystanders offered affiliation to their aggressor friends and the victims
      of their friends, while male bystanders offered affiliation to their victim
      friends and the aggressors of their friends. For both sexes, bystander
      affiliation resulted in a subsequent interaction pattern that is expected for
      direct reconciliation. Bystander affiliation offered to the opponent's friend was
      more likely to lead to affiliation among opponents in their subsequent
      interaction. Also, tolerance levels among former opponents were reset to normal
      levels. In conclusion, this study provides strong evidence for the relationship
      repair hypothesis, moderate evidence for the consolation hypothesis and no
      evidence for the self-protection hypothesis. Furthermore, that bystanders can
      repair a relationship on behalf of their friend indicates that recipient
      chimpanzees are aware of the relationships between others, even when they are not
      kin. This presents a mechanism through which chimpanzees may gain benefits from
      social knowledge.

PMID- 21085593
TI  - Enrichment map: a network-based method for gene-set enrichment visualization and
      interpretation.
AB  - BACKGROUND: Gene-set enrichment analysis is a useful technique to help
      functionally characterize large gene lists, such as the results of gene
      expression experiments. This technique finds functionally coherent gene-sets,
      such as pathways, that are statistically over-represented in a given gene list.
      Ideally, the number of resulting sets is smaller than the number of genes in the
      list, thus simplifying interpretation. However, the increasing number and
      redundancy of gene-sets used by many current enrichment analysis software works
      against this ideal. PRINCIPAL FINDINGS: To overcome gene-set redundancy and help
      in the interpretation of large gene lists, we developed "Enrichment Map", a
      network-based visualization method for gene-set enrichment results. Gene-sets are
      organized in a network, where each set is a node and edges represent gene overlap
      between sets. Automated network layout groups related gene-sets into network
      clusters, enabling the user to quickly identify the major enriched functional
      themes and more easily interpret the enrichment results. CONCLUSIONS: Enrichment
      Map is a significant advance in the interpretation of enrichment analysis. Any
      research project that generates a list of genes can take advantage of this
      visualization framework. Enrichment Map is implemented as a freely available and
      user friendly plug-in for the Cytoscape network visualization software
      (http://baderlab.org/Software/EnrichmentMap/).

PMID- 21085594
TI  - Purification of reversibly oxidized proteins (PROP) reveals a redox switch
      controlling p38 MAP kinase activity.
AB  - Oxidation of cysteine residues of proteins is emerging as an important means of
      regulation of signal transduction, particularly of protein kinase function. Tools
      to detect and quantify cysteine oxidation of proteins have been a limiting factor
      in understanding the role of cysteine oxidation in signal transduction. As an
      example, the p38 MAP kinase is activated by several stress-related stimuli that
      are often accompanied by in vitro generation of hydrogen peroxide. We noted that
      hydrogen peroxide inhibited p38 activity despite paradoxically increasing the
      activating phosphorylation of p38. To address the possibility that cysteine
      oxidation may provide a negative regulatory effect on p38 activity, we developed
      a biochemical assay to detect reversible cysteine oxidation in intact cells. This
      procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen
      peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis
      of the potential target cysteines showed that oxidation occurred preferentially
      on residues near the surface of the p38 molecule. Cysteine oxidation thus
      controls a functional redox switch regulating the intensity or duration of p38
      activity that would not be revealed by immunodetection of phosphoprotein commonly
      interpreted as reflective of p38 activity.

PMID- 21085595
TI  - Cystatin C deficiency promotes epidermal dysplasia in K14-HPV16 transgenic mice.
AB  - BACKGROUND: Cysteine protease cathepsins are important in extracellular matrix
      protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins
      are protected from tumor progression in several animal models, suggesting that
      the regulation of cathepsin activities controls the growth of various malignant
      tumors. METHODS AND RESULTS: We tested the role of cathepsins using a mouse model
      of multistage epithelial carcinogenesis, in which the human keratin-14
      promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16)
      early region E6/E7 transgenes. During the progression of premalignant dysplasia,
      we observed increased expression of cysteine protease cathepsin S, but
      concomitantly reduced expression of cathepsin endogenous inhibitor cystatin C in
      the skin tissue extract. Absence of cystatin C in these transgenic mice resulted
      in more progression of dysplasia to carcinoma in situ on the face, ear, chest,
      and tail. Chest and ear skin extract real time PCR and immunoblot analysis, mouse
      serum sample ELISA, tissue immunohistological analysis, and tissue extract
      mediated in vitro elastinolysis and collagenolysis assays demonstrated that
      cystatin C deficiency significantly increased cathepsin expression and activity.
      In skin from both the chest and ear, we found that the absence of cystatin C
      reduced epithelial cell apoptosis but increased proliferation. From the same
      tissue preparations, we detected significantly higher levels of pro-angiogenic
      laminin 5-derived gamma2 peptides and concurrently increased neovascularization
      in cystatin C-deficient mice, compared to those from wild-type control mice.
      CONCLUSION: Enhanced cathepsin expression and activity in cystatin C-deficient
      mice contributed to the progression of dysplasia by altering premalignant tissue
      epithelial proliferation, apoptosis, and neovascularization.

PMID- 21085596
TI  - Genomic runs of homozygosity record population history and consanguinity.
AB  - The human genome is characterised by many runs of homozygous genotypes, where
      identical haplotypes were inherited from each parent. The length of each run is
      determined partly by the number of generations since the common ancestor:
      offspring of cousin marriages have long runs of homozygosity (ROH), while the
      numerous shorter tracts relate to shared ancestry tens and hundreds of
      generations ago. Human populations have experienced a wide range of demographic
      histories and hold diverse cultural attitudes to consanguinity. In a global
      population dataset, genome-wide analysis of long and shorter ROH allows
      categorisation of the mainly indigenous populations sampled here into four major
      groups in which the majority of the population are inferred to have: (a) recent
      parental relatedness (south and west Asians); (b) shared parental ancestry
      arising hundreds to thousands of years ago through long term isolation and
      restricted effective population size (N(e)), but little recent inbreeding
      (Oceanians); (c) both ancient and recent parental relatedness (Native Americans);
      and (d) only the background level of shared ancestry relating to continental N(e)
      (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan
      African agriculturalists), and the occasional cryptically inbred individual.
      Moreover, individuals can be positioned along axes representing this demographic
      historic space. Long runs of homozygosity are therefore a globally widespread and
      under-appreciated characteristic of our genomes, which record past consanguinity
      and population isolation and provide a distinctive record of the demographic
      history of an individual's ancestors. Individual ROH measures will also allow
      quantification of the disease risk arising from polygenic recessive effects.

PMID- 21085597
TI  - Matrix rigidity induces osteolytic gene expression of metastatic breast cancer
      cells.
AB  - Nearly 70% of breast cancer patients with advanced disease will develop bone
      metastases. Once established in bone, tumor cells produce factors that cause
      changes in normal bone remodeling, such as parathyroid hormone-related protein
      (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to
      resorb bone, the environmental factors driving tumor cells to express PTHrP in
      the early stages of development of metastatic bone disease are unknown. In this
      study, we have shown that tumor cells known to metastasize to bone respond to 2D
      substrates with rigidities comparable to that of the bone microenvironment by
      increasing expression and production of PTHrP. The cellular response is regulated
      by Rho-dependent actomyosin contractility mediated by TGF-beta signaling.
      Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic
      approaches decreased PTHrP expression. Furthermore, cells expressing a dominant
      negative form of the TGF-beta receptor did not respond to substrate rigidity, and
      inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-beta.
      These observations suggest a role for the differential rigidity of the
      mineralized bone microenvironment in early stages of tumor-induced osteolysis,
      which is especially important in metastatic cancer since many cancers (such as
      those of the breast and lung) preferentially metastasize to bone.

PMID- 21085598
TI  - Absolute pitch: effects of timbre on note-naming ability.
AB  - BACKGROUND: Absolute pitch (AP) is the ability to identify or produce isolated
      musical tones. It is evident primarily among individuals who started music
      lessons in early childhood. Because AP requires memory for specific pitches as
      well as learned associations with verbal labels (i.e., note names), it represents
      a unique opportunity to study interactions in memory between linguistic and
      nonlinguistic information. One untested hypothesis is that the pitch of voices
      may be difficult for AP possessors to identify. A musician's first instrument may
      also affect performance and extend the sensitive period for acquiring accurate
      AP. METHODS/PRINCIPAL FINDINGS: A large sample of AP possessors was recruited on
      line. Participants were required to identity test tones presented in four
      different timbres: piano, pure tone, natural (sung) voice, and synthesized voice.
      Note-naming accuracy was better for non-vocal (piano and pure tones) than for
      vocal (natural and synthesized voices) test tones. This difference could not be
      attributed solely to vibrato (pitch variation), which was more pronounced in the
      natural voice than in the synthesized voice. Although starting music lessons by
      age 7 was associated with enhanced note-naming accuracy, equivalent abilities
      were evident among listeners who started music lessons on piano at a later age.
      CONCLUSIONS/SIGNIFICANCE: Because the human voice is inextricably linked to
      language and meaning, it may be processed automatically by voice-specific
      mechanisms that interfere with note naming among AP possessors. Lessons on piano
      or other fixed-pitch instruments appear to enhance AP abilities and to extend the
      sensitive period for exposure to music in order to develop accurate AP.

PMID- 21085599
TI  - Enhancing oral vaccine potency by targeting intestinal M cells.
AB  - The immune system in the gastrointestinal tract plays a crucial role in the
      control of infection, as it constitutes the first line of defense against mucosal
      pathogens. The attractive features of oral immunization have led to the
      exploration of a variety of oral delivery systems. However, none of these oral
      delivery systems have been applied to existing commercial vaccines. To overcome
      this, a new generation of oral vaccine delivery systems that target antigens to
      gut-associated lymphoid tissue is required. One promising approach is to exploit
      the potential of microfold (M) cells by mimicking the entry of pathogens into
      these cells. Targeting specific receptors on the apical surface of M cells might
      enhance the entry of antigens, initiating the immune response and consequently
      leading to protection against mucosal pathogens. In this article, we briefly
      review the challenges associated with current oral vaccine delivery systems and
      discuss strategies that might potentially target mouse and human intestinal M
      cells.

PMID- 21085600
TI  - The role of lactic acid adsorption by ion exchange chromatography.
AB  - BACKGROUND: The polyacrylic resin Amberlite IRA-67 is a promising adsorbent for
      lactic acid extraction from aqueous solution, but little systematic research has
      been devoted to the separation efficiency of lactic acid under different
      operating conditions. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we
      investigated the effects of temperature, resin dose and lactic acid loading
      concentration on the adsorption of lactic acid by Amberlite IRA-67 in batch
      kinetic experiments. The obtained kinetic data followed the pseudo-second order
      model well and both the equilibrium and ultimate adsorption slightly decreased
      with the increase of the temperature at 293-323K and 42.5 g/liter lactic acid
      loading concentration. The adsorption was a chemically heterogeneous process with
      a mean free energy value of 12.18 kJ/mol. According to the Boyd(_)plot, the
      lactic acid uptake process was primarily found to be an intraparticle diffusion
      at a lower concentration (<50 g/liter) but a film diffusion at a higher
      concentration (>70 g/liter). The values of effective diffusion coefficient D(i)
      increased with temperature. By using our Equation (21), the negative values of
      DeltaG degrees  and DeltaH degrees  revealed that the adsorption process was
      spontaneous and exothermic. Moreover, the negative value of DeltaS degrees 
      reflected the decrease of solid-liquid interface randomness at the solid-liquid
      interface when adsorbing lactic acid on IRA-67. CONCLUSIONS/SIGNIFICANCE: With
      the weakly basic resin IRA-67, in situ product removal of lactic acid can be
      accomplished especially from an open and thermophilic fermentation system without
      sterilization.

PMID- 21085601
TI  - Host cell invasion and virulence mediated by Candida albicans Ssa1.
AB  - Candida albicans Ssa1 and Ssa2 are members of the HSP70 family of heat shock
      proteins that are expressed on the cell surface and function as receptors for
      antimicrobial peptides such as histatins. We investigated the role of Ssa1 and
      Ssa2 in mediating pathogenic host cell interactions and virulence. A C. albicans
      ssa1Delta/Delta mutant had attenuated virulence in murine models of disseminated
      and oropharyngeal candidiasis, whereas an ssa2Delta/Delta mutant did not. In
      vitro studies revealed that the ssa1Delta/Delta mutant caused markedly less
      damage to endothelial cells and oral epithelial cell lines. Also, the
      ssa1Delta/Delta mutant had defective binding to endothelial cell N-cadherin and
      epithelial cell E-cadherin, receptors that mediate host cell endocytosis of C.
      albicans. As a result, this mutant had impaired capacity to induce its own
      endocytosis by endothelial cells and oral epithelial cells. Latex beads coated
      with recombinant Ssa1 were avidly endocytosed by both endothelial cells and oral
      epithelial cells, demonstrating that Ssa1 is sufficient to induce host cell
      endocytosis. These results indicate that Ssa1 is a novel invasin that binds to
      host cell cadherins, induces host cell endocytosis, and is critical for C.
      albicans to cause maximal damage to host cells and induce disseminated and
      oropharyngeal disease.

PMID- 21085602
TI  - Nme gene family evolutionary history reveals pre-metazoan origins and high
      conservation between humans and the sea anemone, Nematostella vectensis.
AB  - BACKGROUND: The Nme gene family is involved in multiple physiological and
      pathological processes such as cellular differentiation, development, metastatic
      dissemination, and cilia functions. Despite the known importance of Nme genes and
      their use as clinical markers of tumor aggressiveness, the associated cellular
      mechanisms remain poorly understood. Over the last 20 years, several non
      vertebrate model species have been used to investigate Nme functions. However,
      the evolutionary history of the family remains poorly understood outside the
      vertebrate lineage. The aim of the study was thus to elucidate the evolutionary
      history of the Nme gene family in Metazoans. METHODOLOGY/PRINCIPAL FINDINGS:
      Using a total of 21 eukaryote species including 14 metazoans, the evolutionary
      history of Nme genes was reconstructed in the metazoan lineage. We demonstrated
      that the complexity of the Nme gene family, initially thought to be restricted to
      chordates, was also shared by the metazoan ancestor. We also provide evidence
      suggesting that the complexity of the family is mainly a eukaryotic innovation,
      with the exception of Nme8 that is likely to be a choanoflagellate/metazoan
      innovation. Highly conserved gene structure, genomic linkage, and protein domains
      were identified among metazoans, some features being also conserved in
      eukaryotes. When considering the entire Nme family, the starlet sea anemone is
      the studied metazoan species exhibiting the most conserved gene and protein
      sequence features with humans. In addition, we were able to show that most of the
      proteins known to interact with human NME proteins were also found in starlet sea
      anemone. CONCLUSION/SIGNIFICANCE: Together, our observations further support the
      association of Nme genes with key cellular functions that have been conserved
      throughout metazoan evolution. Future investigations of evolutionarily conserved
      Nme gene functions using the starlet sea anemone could shed new light on a wide
      variety of key developmental and cellular processes.

PMID- 21085603
TI  - Screening for familial APP mutations in sporadic cerebral amyloid angiopathy.
AB  - BACKGROUND: Advances in genetic technology have revealed that variation in the
      same gene can cause both rare familial and common sporadic forms of the same
      disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic
      intracerebral hemorrhage (ICH) in the elderly, can also occur in families in an
      autosomal dominant pattern. The majority of affected families harbor mutations in
      the Beta amyloid Peptide (Abeta) coding region of the gene for amyloid precursor
      protein (APP) or have duplications of chromosomal segments containing APP.
      METHODOLOGY/PRINCIPAL FINDINGS: A total of 58 subjects with a diagnosis of
      probable or definite CAA according to validated criteria were included in the
      present study. We sequenced the Abeta coding region of APP in 58 individuals and
      performed multiplex ligation-dependent probe amplification to determine APP gene
      dosage in 60. No patient harbored a known or novel APP mutation or gene
      duplication. The frequency of mutations investigated in the present study is
      estimated to range from 0% to 8% in individuals with probable CAA in the general
      population, based on the ascertained sample size. CONCLUSIONS/SIGNIFICANCE: We
      found no evidence that variants at loci associated with familial CAA play a role
      in sporadic CAA. Based on our findings, these rare highly-penetrant mutations are
      unlikely to be seen in sporadic CAA patients. Therefore, our results do not
      support systematic genetic screening of CAA patients who lack a strong family
      history of hemorrhage or dementia.

PMID- 21085604
TI  - Transient increase in cyclic AMP localized to macrophage phagosomes.
AB  - Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The
      importance of spatially localized intracellular gradients of cAMP is increasingly
      appreciated. Previous work in macrophages has shown that cAMP is produced during
      phagocytosis and that elevated cAMP levels suppress host defense functions,
      including generation of proinflammatory mediators, phagocytosis and killing.
      However, the spatial and kinetic characteristics of cAMP generation in
      phagocytosing macrophages have yet to be examined. Using a Forster resonance
      energy transfer (FRET)-based cAMP biosensor, we measured the generation of cAMP
      in live macrophages. We detected no difference in bulk intracellular cAMP levels
      between resting cells and cells actively phagocytosing IgG-opsonized particles.
      However, analysis with the biosensor revealed a rapid decrease in FRET signal
      corresponding to a transient burst of cAMP production localized to the forming
      phagosome. cAMP levels returned to baseline after the particle was internalized.
      These studies indicate that localized increases in cAMP accompany phagosome
      formation and provide a framework for a more complete understanding of how cAMP
      regulates macrophage host defense functions.

PMID- 21085605
TI  - T-lymphocyte responses to intestinally absorbed antigens can contribute to
      adipose tissue inflammation and glucose intolerance during high fat feeding.
AB  - BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues,
      which increases the risk for insulin resistance. Animal models suggest that T
      lymphocyte infiltration is an important early step, although it is unclear why
      these cells are attracted. We have recently demonstrated that dietary
      triglycerides, major components of high fat diets, promote intestinal absorption
      of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on
      chylomicrons, which are prominently cleared in adipose tissues. We hypothesized
      that intestinally absorbed gut antigens may cause T-lymphocyte associated
      inflammation in adipose tissue. METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride
      absorption promoted intestinal absorption of OVA into adipose tissue, in a
      chylomicron-dependent manner. Absorption tended to be higher in mesenteric than
      subcutaneous adipose tissue, and was lowest in gonadal tissue. OVA
      immunoreactivity was detected in stromal vascular cells, including endothelial
      cells. In OVA-sensitized mice, OVA feeding caused marked accumulation of CD3+ and
      osteopontin+ cells in mesenteric adipose tissue. The accumulating T-lymphocytes
      were mainly CD4+. As expected, high-fat (60% kCal) diets promoted mesenteric
      adipose tissue inflammation compared to low-fat diets (10% Kcal), as reflected by
      increased expression of osteopontin and interferon-gamma. Immune responses to
      dietary OVA further increased diet-induced osteopontin and interferon-gamma
      expression in mesenteric adipose. Inflammatory gene expression in subcutaneous
      tissue did not respond significantly to OVA or dietary fat content. Lastly,
      whereas OVA responses did not significantly affect bodyweight or adiposity, they
      significantly impaired glucose tolerance. CONCLUSIONS/SIGNIFICANCE: Our results
      suggest that loss or lack of immunological tolerance to intestinally absorbed T
      lymphocyte antigens can contribute to mesenteric adipose tissue inflammation and
      defective glucose metabolism during high-fat dieting.

PMID- 21085606
TI  - Functional interaction between acyl-CoA synthetase 4, lipooxygenases and
      cyclooxygenase-2 in the aggressive phenotype of breast cancer cells.
AB  - The acyl-CoA synthetase 4 (ACSL4) is increased in breast cancer, colon and
      hepatocellular carcinoma. ACSL4 mainly esterifies arachidonic acid (AA) into
      arachidonoyl-CoA, reducing free AA intracellular levels, which is in
      contradiction with the need for AA metabolites in tumorigenesis. Therefore, the
      causal role of ACSL4 is still not established. This study was undertaken to
      determine the role of ACSL4 in AA metabolic pathway in breast cancer cells. The
      first novel finding is that ACSL4 regulates the expression of cyclooxygenase-2
      (COX-2) and the production of prostaglandin in MDA-MB-231 cells. We also found
      that ACSL4 is significantly up-regulated in the highly aggressive MDA-MB-231
      breast cancer cells. In terms of its overexpression and inhibition, ACSL4 plays a
      causal role in the control of the aggressive phenotype. These results were
      confirmed by the increase in the aggressive behaviour of MCF-7 cells stably
      transfected with a Tet-off ACSL4 vector. Concomitantly, another significant
      finding was that intramitochondrial AA levels are significantly higher in the
      aggressive cells. Thus, the esterification of AA by ACSL4 compartmentalizes the
      release of AA in mitochondria, a mechanism that serves to drive the specific
      lipooxygenase metabolization of the fatty acid. To our knowledge, this is the
      first report that ACSL4 expression controls both lipooxygenase and cyclooxygenase
      metabolism of AA. Thus, this functional interaction represents an integrated
      system that regulates the proliferating and metastatic potential of cancer cells.
      Therefore, the development of combinatory therapies that profit from the ACSL4,
      lipooxygenase and COX-2 synergistic action may allow for lower medication doses
      and avoidance of side effects.

PMID- 21085607
TI  - Speeded near infrared spectroscopy (NIRS) response detection.
AB  - The hemodynamic response measured by Near Infrared Spectroscopy (NIRS) is
      temporally delayed from the onset of the underlying neural activity. As a
      consequence, NIRS based brain-computer-interfaces (BCIs) and neurofeedback
      learning systems, may have a latency of several seconds in responding to a change
      in participants' behavioral or mental states, severely limiting the practical use
      of such systems. To explore the possibility of reducing this delay, we used a
      multivariate pattern classification technique (linear support vector machine,
      SVM) to decode the true behavioral state from the measured neural signal and
      systematically evaluated the performance of different feature spaces (signal
      history, history gradient, oxygenated or deoxygenated hemoglobin signal and
      spatial pattern). We found that the latency to decode a change in behavioral
      state can be reduced by 50% (from 4.8 s to 2.4 s), which will enhance the
      feasibility of NIRS for real-time applications.

PMID- 21085608
TI  - Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A
      mediated imbalance of inflammatory cytokines.
AB  - Understanding how hepatitis C virus (HCV) induces and circumvents the host's
      natural killer (NK) cell-mediated immunity is of critical importance in efforts
      to design effective therapeutics. We report here the decreased expression of the
      NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell
      mediated responses. We show that chronic HCV infection is associated with
      expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules,
      on hepatocytes. However, NKG2D expression is downmodulated on circulating NK
      cells, and consequently NK cell-mediated cytotoxic capacity and interferon-gamma
      production are impaired. Using an endotoxin-free recombinant NS5A protein, we
      show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4)
      promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12
      production. In turn, IL-10 triggers secretion of TGFbeta which downmodulates
      NKG2D expression on NK cells, leading to their impaired effector functions.
      Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce
      the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can
      antagonize the TGFbeta effect and restore normal NKG2D expression on NK cells. We
      conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV
      infection, and demonstrate that this alteration can be prevented by exogenous IL
      15, which could represent a meaningful adjuvant for therapeutic intervention.

PMID- 21085609
TI  - Leishmania major survival in selective Phlebotomus papatasi sand fly vector
      requires a specific SCG-encoded lipophosphoglycan galactosylation pattern.
AB  - Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ
      greatly in their ability to support different parasite species or strains in the
      laboratory: while some show considerable selectivity, others are more permissive.
      In "selective" sand flies, Leishmania binding and survival in the fly midgut
      typically depends upon the abundant promastigote surface adhesin
      lipophosphoglycan (LPG), which exhibits species- and strain-specific
      modifications of the dominant phosphoglycan (PG) repeat units. For the
      "selective" fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications
      (scGal) of PG repeats play key roles in parasite binding. We probed the
      specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular
      Pattern) through studies of natural isolates exhibiting a wide range of
      galactosylation patterns, and of a panel of isogenic L. major engineered to
      express similar scGal-LPG diversity by transfection of SCG-encoded beta1,3
      galactosyltransferases with different activities. Surprisingly, both 'poly-scGal'
      and 'null-scGal' lines survived poorly relative to PpapJ-sympatric L. major FV1
      and other 'mono-scGal' lines. However, survival of all lines was equivalent in P.
      duboscqi, which naturally transmit L. major strains bearing 'null-scGal'-LPG
      PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for
      PpapJ midgut survival by engineering Leishmania donovani, which normally express
      unsubstituted LPG, to express a 'PpapJ-optimal' scGal-LPG PAMP. Unexpectedly,
      these "L. major FV1-cloaked" L. donovani-SCG lines remained unable to survive
      within PpapJ flies. These studies establish that midgut survival of L. major in
      PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific
      'mono-scGal' pattern. However, failure of 'mono-scGal' L. donovani-SCG lines to
      survive in selective PpapJ flies suggests a requirement for an additional, as yet
      unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP
      and additional factor(s) with sand fly midgut receptors may determine whether a
      given sand fly host is "selective" or "permissive", with important consequences
      to both disease transmission and the natural co-evolution of sand flies and
      Leishmania.

PMID- 21085610
TI  - Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix
      protein is important for viral budding.
AB  - Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma
      membrane. Matrix is the major structural protein in paramyxoviruses that mediates
      viral assembly and budding. Curiously, the matrix proteins of a few
      paramyxoviruses have been found in the nucleus, although the biological function
      associated with this nuclear localization remains obscure. We report here that
      the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M) protein and
      associated post-translational modification play a critical role in matrix
      mediated virus budding. Nipah virus (NiV) is a highly pathogenic emerging
      paramyxovirus that causes fatal encephalitis in humans, and is classified as a
      Biosafety Level 4 (BSL4) pathogen. During live NiV infection, NiV-M was first
      detected in the nucleus at early stages of infection before subsequent
      localization to the cytoplasm and the plasma membrane. Mutations in the putative
      bipartite nuclear localization signal (NLS) and the leucine-rich nuclear export
      signal (NES) found in NiV-M impaired its nuclear-cytoplasmic trafficking and also
      abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual
      functions: its positive charge was important for mediating nuclear import, and it
      was also a potential site for monoubiquitination which regulates nuclear export
      of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding
      whereas depletion of free ubiquitin in the cell (via proteasome inhibitors)
      resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah
      virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an
      FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral
      titers with an IC(50) of 2.7 nM, which is 100-fold less than the peak plasma
      concentration that can be achieved in humans. This opens up the possibility of
      using an "off-the-shelf" therapeutic against acute NiV infection.

PMID- 21085611
TI  - Escherichia coli global gene expression in urine from women with urinary tract
      infection.
AB  - Murine models of urinary tract infection (UTI) have provided substantial data
      identifying uropathogenic E. coli (UPEC) virulence factors and assessing their
      expression in vivo. However, it is unclear how gene expression in these animal
      models compares to UPEC gene expression during UTI in humans. To address this, we
      used a UPEC strain CFT073-specific microarray to measure global gene expression
      in eight E. coli isolates monitored directly from the urine of eight women
      presenting at a clinic with bacteriuria. The resulting gene expression profiles
      were compared to those of the same E. coli isolates cultured statically to
      exponential phase in pooled, sterilized human urine ex vivo. Known fitness
      factors, including iron acquisition and peptide transport systems, were highly
      expressed during human UTI and support a model in which UPEC replicates rapidly
      in vivo. While these findings were often consistent with previous data obtained
      from the murine UTI model, host-specific differences were observed. Most
      strikingly, expression of type 1 fimbrial genes, which are among the most highly
      expressed genes during murine experimental UTI and encode an essential virulence
      factor for this experimental model, was undetectable in six of the eight E. coli
      strains from women with UTI. Despite the lack of type 1 fimbrial expression in
      the urine samples, these E. coli isolates were generally capable of expressing
      type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine
      infection. The findings presented here provide insight into the metabolic and
      pathogenic profile of UPEC in urine from women with UTI and represent the first
      transcriptome analysis for any pathogenic E. coli during a naturally occurring
      infection in humans.

PMID- 21085612
TI  - HIV-1 induces DCIR expression in CD4+ T cells.
AB  - The C-type lectin receptor DCIR, which has been shown very recently to act as an
      attachment factor for HIV-1 in dendritic cells, is expressed predominantly on
      antigen-presenting cells. However, this concept was recently challenged by the
      discovery that DCIR can also be detected in CD4(+) T cells found in the synovial
      tissue from rheumatoid arthritis (RA) patients. Given that RA and HIV-1
      infections share common features such as a chronic inflammatory condition and
      polyclonal immune hyperactivation status, we hypothesized that HIV-1 could
      promote DCIR expression in CD4(+) T cells. We report here that HIV-1 drives DCIR
      expression in human primary CD4(+) T cells isolated from patients (from both
      aviremic/treated and viremic/treatment naive persons) and cells acutely infected
      in vitro (seen in both virus-infected and uninfected cells). Soluble factors
      produced by virus-infected cells are responsible for the noticed DCIR up
      regulation on uninfected cells. Infection studies with Vpr- or Nef-deleted
      viruses revealed that these two viral genes are not contributing to the mechanism
      of DCIR induction that is seen following acute infection of CD4(+) T cells with
      HIV-1. Moreover, we report that DCIR is linked to caspase-dependent (induced by a
      mitochondria-mediated generation of free radicals) and -independent intrinsic
      apoptotic pathways (involving the death effector AIF). Finally, we demonstrate
      that the higher surface expression of DCIR in CD4(+) T cells is accompanied by an
      enhancement of virus attachment/entry, replication and transfer. This study shows
      for the first time that HIV-1 induces DCIR membrane expression in CD4(+) T cells,
      a process that might promote virus dissemination throughout the infected
      organism.

PMID- 21085614
TI  - MAP kinase phosphatase-2 plays a critical role in response to infection by
      Leishmania mexicana.
AB  - In this study we generated a novel dual specific phosphatase 4 (DUSP4) deletion
      mouse using a targeted deletion strategy in order to examine the role of MAP
      kinase phosphatase-2 (MKP-2) in immune responses. Lipopolysaccharide (LPS)
      induced a rapid, time and concentration-dependent increase in MKP-2 protein
      expression in bone marrow-derived macrophages from MKP-2(+/+) but not from MKP-2(
      /-) mice. LPS-induced JNK and p38 MAP kinase phosphorylation was significantly
      increased and prolonged in MKP-2(-/-) macrophages whilst ERK phosphorylation was
      unaffected. MKP-2 deletion also potentiated LPS-stimulated induction of the
      inflammatory cytokines, IL-6, IL-12p40, TNF-alpha, and also COX-2 derived PGE(2)
      production. However surprisingly, in MKP-2(-/-) macrophages, there was a marked
      reduction in LPS or IFNgamma-induced iNOS and nitric oxide release and enhanced
      basal expression of arginase-1, suggesting that MKP-2 may have an additional
      regulatory function significant in pathogen-mediated immunity. Indeed, following
      infection with the intracellular parasite Leishmania mexicana, MKP-2(-/-) mice
      displayed increased lesion size and parasite burden, and a significantly modified
      Th1/Th2 bias compared with wild-type counterparts. However, there was no
      intrinsic defect in MKP-2(-/-) T cell function as measured by anti-CD3 induced
      IFN-gamma production. Rather, MKP-2(-/-) bone marrow-derived macrophages were
      found to be inherently more susceptible to infection with Leishmania mexicana, an
      effect reversed following treatment with the arginase inhibitor nor-NOHA. These
      findings show for the first time a role for MKP-2 in vivo and demonstrate that
      MKP-2 may be essential in orchestrating protection against intracellular
      infection at the level of the macrophage.

PMID- 21085613
TI  - Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory
      cytokines independently of TLR4.
AB  - Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and
      potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic
      cells (DC) play a key role in the initiation and instruction of adaptive
      immunity, but the effects of PLY on DC have not been widely investigated.
      Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not
      induce cytokine secretion. These effects have functional significance as adoptive
      transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T
      cell proliferation than transfer of DC exposed to antigen alone. PLY synergized
      with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL
      23, IL-6, IL-1beta, IL-1alpha and TNF-alpha by DC and enhanced cytokines
      including IL-17A and IFN-gamma by splenocytes. PLY-induced DC maturation and
      cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and
      IFN-gamma are required for protective immunity to pneumococcal infection and
      intranasal infection of mice with PLY-deficient pneumococci induced significantly
      less IFN-gamma and IL-17A in the lungs compared to infection with wild-type
      bacteria. IL-1beta plays a key role in promoting IL-17A and was previously shown
      to mediate protection against pneumococcal infection. The enhancement of IL-1beta
      secretion by whole live S. pneumoniae and by PLY in DC required NLRP3,
      identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was
      required for protective immunity against respiratory infection with S.
      pneumoniae. These results add significantly to our understanding of the
      interactions between PLY and the immune system.

PMID- 21085615
TI  - Structural basis of HIV-1 neutralization by affinity matured Fabs directed
      against the internal trimeric coiled-coil of gp41.
AB  - The conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR) of HIV
      1 gp41 is transiently exposed during the fusion process by forming a pre-hairpin
      intermediate, thus representing an attractive target for the design of fusion
      inhibitors and neutralizing antibodies. In previous studies we reported a series
      of broadly neutralizing mini-antibodies derived from a synthetic naive human
      combinatorial antibody library by panning against a mimetic of the trimeric N-HR
      coiled coil, followed by affinity maturation using targeted diversification of
      the CDR-H2 loop. Here we report crystal structures of the N-HR mimetic 5-Helix
      with two Fabs that represent the extremes of this series: Fab 8066 is broadly
      neutralizing across a wide panel of B and C type HIV-1 viruses, whereas Fab 8062
      is non-neutralizing. The crystal structures reveal important differences in the
      conformations of the CDR-H2 loops in the complexes that propagate into other
      regions of the antigen-antibody interface, and suggest that both neutralization
      properties and affinity for the target can be attributed, at least in part, to
      the differences in the interactions of the CDR-H2 loops with the antigen.
      Furthermore, modeling of the complex of an N-HR trimer with three Fabs suggests
      that the CDR-H2 loop may be involved in close intermolecular contacts between
      neighboring antibody molecules, and that such contacts may hinder the formation
      of complexes between the N-HR trimer and more than one antibody molecule
      depending on the conformation of the bound CDR-H2 loop which is defined by its
      interactions with antigen. Comparison with the crystal structure of the complex
      of 5-Helix with another neutralizing monoclonal antibody known as D5, derived
      using an entirely different antibody library and panning procedure, reveals
      remarkable convergence in the optimal sequence and conformation of the CDR-H2
      loop.

PMID- 21085617
TI  - Systematic inference of copy-number genotypes from personal genome sequencing
      data reveals extensive olfactory receptor gene content diversity.
AB  - Copy-number variations (CNVs) are widespread in the human genome, but
      comprehensive assignments of integer locus copy-numbers (i.e., copy-number
      genotypes) that, for example, enable discrimination of homozygous from
      heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel
      computational approach with an underlying statistical framework that analyzes the
      depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate
      paired-end and breakpoint junction analysis based CNV-analysis approaches, to
      infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500
      chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The
      assessed copy-number genotypes were highly concordant with our performed qPCR
      experiments (Pearson correlation coefficient 0.94), and with the published
      results of two microarray platforms (95-99% concordance). We further demonstrated
      the utility of CopySeq for analyzing gene regions enriched for segmental
      duplications by comprehensively inferring copy-number genotypes in the CNV
      enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq
      revealed that OR loci display an extensive range of locus copy-numbers across
      individuals, with zero to two copies in some OR loci, and two to nine copies in
      others. Among genetic variants affecting OR loci we identified deleterious
      variants including CNVs and SNPs affecting ~15% and ~20% of the human OR gene
      repertoire, respectively, implying that genetic variants with a possible impact
      on smell perception are widespread. Finally, we found that for several OR loci
      the reference genome appears to represent a minor-frequency variant, implying a
      necessary revision of the OR repertoire for future functional studies. CopySeq
      can ascertain genomic structural variation in specific gene families as well as
      at a genome-wide scale, where it may enable the quantitative evaluation of CNVs
      in genome-wide association studies involving high-throughput sequencing.

PMID- 21085616
TI  - The Gag cleavage product, p12, is a functional constituent of the murine leukemia
      virus pre-integration complex.
AB  - The p12 protein is a cleavage product of the Gag precursor of the murine leukemia
      virus (MLV). Specific mutations in p12 have been described that affect early
      stages of infection, rendering the virus replication-defective. Such mutants
      showed normal generation of genomic DNA but no formation of circular forms, which
      are markers of nuclear entry by the viral DNA. This suggested that p12 may
      function in early stages of infection but the precise mechanism of p12 action is
      not known. To address the function and follow the intracellular localization of
      the wt p12 protein, we generated tagged p12 proteins in the context of a
      replication-competent virus, which allowed for the detection of p12 at early
      stages of infection by immunofluorescence. p12 was found to be distributed to
      discrete puncta, indicative of macromolecular complexes. These complexes were
      localized to the cytoplasm early after infection, and thereafter accumulated
      adjacent to mitotic chromosomes. This chromosomal accumulation was impaired for
      p12 proteins with a mutation that rendered the virus integration-defective.
      Immunofluorescence demonstrated that intracellular p12 complexes co-localized
      with capsid, a known constituent of the MLV pre-integration complex (PIC), and
      immunofluorescence combined with fluorescent in situ hybridization (FISH)
      revealed co-localization of the p12 proteins with the incoming reverse
      transcribed viral DNA. Interactions of p12 with the capsid and with the viral DNA
      were also demonstrated by co-immunoprecipitation. These results imply that p12
      proteins are components of the MLV PIC. Furthermore, a large excess of wt PICs
      did not rescue the defect in integration of PICs derived from mutant p12
      particles, demonstrating that p12 exerts its function as part of this complex.
      Altogether, these results imply that p12 proteins are constituent of the MLV PIC
      and function in directing the PIC from the cytoplasm towards integration.

PMID- 21085619
TI  - Adequate reimbursement is crucial to support cost-effective rapid on-site
      cytopathology evaluations.

PMID- 21085618
TI  - Lobe specific Ca2+-calmodulin nano-domain in neuronal spines: a single molecule
      level analysis.
AB  - Calmodulin (CaM) is a ubiquitous Ca(2+) buffer and second messenger that affects
      cellular function as diverse as cardiac excitability, synaptic plasticity, and
      gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca(2+)
      dependent processes that underlie memory formation: long-term potentiation (LTP)
      and long-term depression (LTD). Induction of LTP and LTD require activation of
      Ca(2+)-CaM-dependent enzymes: Ca(2+)/CaM-dependent kinase II (CaMKII) and
      calcineurin, respectively. Yet, it remains unclear as to how Ca(2+) and CaM
      produce these two opposing effects, LTP and LTD. CaM binds 4 Ca(2+) ions: two in
      its N-terminal lobe and two in its C-terminal lobe. Experimental studies have
      shown that the N- and C-terminal lobes of CaM have different binding kinetics
      toward Ca(2+) and its downstream targets. This may suggest that each lobe of CaM
      differentially responds to Ca(2+) signal patterns. Here, we use a novel event
      driven particle-based Monte Carlo simulation and statistical point pattern
      analysis to explore the spatial and temporal dynamics of lobe-specific Ca(2+)-CaM
      interaction at the single molecule level. We show that the N-lobe of CaM, but not
      the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive
      to the location of Ca(2+) channels, and to the microscopic injection rate of
      Ca(2+) ions. We also demonstrate that Ca(2+) saturation takes place via two
      different pathways depending on the Ca(2+) injection rate, one dominated by the N
      terminal lobe, and the other one by the C-terminal lobe. Taken together, these
      results suggest that the two lobes of CaM function as distinct Ca(2+) sensors
      that can differentially transduce Ca(2+) influx to downstream targets. We discuss
      a possible role of the N-terminal lobe-specific Ca(2+)-CaM nano-domain in CaMKII
      activation required for the induction of synaptic plasticity.

PMID- 21085620
TI  - Characterization of synthetic nanocrystalline mackinawite: crystal structure,
      particle size, and specific surface area.
AB  - Iron sulfide was synthesized by reacting aqueous solutions of sodium sulfide and
      ferrous chloride for 3 days. By X-ray powder diffraction (XRPD), the resultant
      phase was determined to be primarily nanocrystalline mackinawite (space group:
      P4/nmm) with unit cell parameters a = b = 3.67 A and c = 5.20 A. Iron K-edge XAS
      analysis also indicated the dominance of mackinawite. Lattice expansion of
      synthetic mackinawite was observed along the c-axis relative to well-crystalline
      mackinawite. Compared with relatively short-aged phase, the mackinawite prepared
      here was composed of larger crystallites with less elongated lattice spacings.
      The direct observation of lattice fringes by HR-TEM verified the applicability of
      Bragg diffraction in determining the lattice parameters of nanocrystalline
      mackinawite from XRPD patterns. Estimated particle size and external specific
      surface area (SSA(ext)) of nanocrystalline mackinawite varied significantly with
      the methods used. The use of Scherrer equation for measuring crystallite size
      based on XRPD patterns is limited by uncertainty of the Scherrer constant (K) due
      to the presence of polydisperse particles. The presence of polycrystalline
      particles may also lead to inaccurate particle size estimation by Scherrer
      equation, given that crystallite and particle sizes are not equivalent. The TEM
      observation yielded the smallest SSA(ext) of 103 m(2)/g. This measurement was not
      representative of dispersed particles due to particle aggregation from drying
      during sample preparation. In contrast, EGME method and PCS measurement yielded
      higher SSA(ext) (276-345 m(2)/g by EGME and 424 +/- 130 m(2)/g by PCS). These
      were in reasonable agreement with those previously measured by the methods
      insensitive to particle aggregation.

PMID- 21085621
TI  - A Case-Series Test of the Interactive Two-step Model of Lexical Access:
      Predicting Word Repetition from Picture Naming.
AB  - Lexical access in language production, and particularly pathologies of lexical
      access, are often investigated by examining errors in picture naming and word
      repetition. In this article, we test a computational approach to lexical access,
      the two-step interactive model, by examining whether the model can quantitatively
      predict the repetition-error patterns of 65 aphasic subjects from their naming
      errors. The model's characterizations of the subjects' naming errors were taken
      from the companion paper to this one (Schwartz, Dell, N. Martin, Gahl & Sobel,
      2006), and their repetition was predicted from the model on the assumption that
      naming involves two error prone steps, word and phonological retrieval, whereas
      repetition only creates errors in the second of these steps. A version of the
      model in which lexical-semantic and lexical-phonological connections could be
      independently lesioned was generally successful in predicting repetition for the
      aphasics. An analysis of the few cases in which model predictions were inaccurate
      revealed the role of input phonology in the repetition task.

PMID- 21085622
TI  - COOPERATIVE GROUP TRIALS - SOUTHWEST ONCOLOGY GROUP (SWOG) INNOVATIONS IN
      ADVANCED PROSTATE CANCER.
AB  - The major goals of the SWOG-GU committee in the area of advanced prostate cancer
      are to improve the survival and quality of life of patients with advanced
      prostate cancer. SWOG trials have examined the role of combined androgen
      blockade, intermittent androgen deprivation, and the early application of
      chemotherapy in castration-naive disease. In addition, they have contributed to
      advancing the current chemotherapy standard of docetaxel plus prednisone, and
      ongoing trials seek to improve upon that standard. Finally, surrogate endpoints
      have been identified and markers of treatment response or resistance with novel
      technology are under active investigation. This review highlights findings from
      recent SWOG clinical trials for advanced prostate cancer, emphasizing the
      clinical impact and future applications of the data.

PMID- 21085623
TI  - Synthesis of Enantioenriched alpha,alpha-Disubstituted Cyclopentenes Catalyzed by
      N-Heterocyclic Carbenes.
AB  - The desymmetrization of 1,3-diketones using N-heterocyclic carbenes results in
      the formation of highly enantioenriched cyclopentenes in good yield. The reaction
      proceeds through a catalytic intramolecular aldol reaction and subsequent beta
      lactone formation. The expulsion of carbon dioxide at mild reaction temperatures
      affords the cyclopentene products.

PMID- 21085624
TI  - On the size and flight diversity of giant pterosaurs, the use of birds as
      pterosaur analogues and comments on pterosaur flightlessness.
AB  - The size and flight mechanics of giant pterosaurs have received considerable
      research interest for the last century but are confused by conflicting
      interpretations of pterosaur biology and flight capabilities. Avian biomechanical
      parameters have often been applied to pterosaurs in such research but, due to
      considerable differences in avian and pterosaur anatomy, have lead to systematic
      errors interpreting pterosaur flight mechanics. Such assumptions have lead to
      assertions that giant pterosaurs were extremely lightweight to facilitate flight
      or, if more realistic masses are assumed, were flightless. Reappraisal of the
      proportions, scaling and morphology of giant pterosaur fossils suggests that bird
      and pterosaur wing structure, gross anatomy and launch kinematics are too
      different to be considered mechanically interchangeable. Conclusions assuming
      such interchangeability--including those indicating that giant pterosaurs were
      flightless--are found to be based on inaccurate and poorly supported assumptions
      of structural scaling and launch kinematics. Pterosaur bone strength and flap
      gliding performance demonstrate that giant pterosaur anatomy was capable of
      generating sufficient lift and thrust for powered flight as well as resisting
      flight loading stresses. The retention of flight characteristics across giant
      pterosaur skeletons and their considerable robustness compared to similarly
      massed terrestrial animals suggest that giant pterosaurs were not flightless.
      Moreover, the term 'giant pterosaur' includes at least two radically different
      forms with very distinct palaeoecological signatures and, accordingly, all but
      the most basic sweeping conclusions about giant pterosaur flight should be
      treated with caution. Reappraisal of giant pterosaur material also reveals that
      the size of the largest pterosaurs, previously suggested to have wingspans up to
      13 m and masses up to 544 kg, have been overestimated. Scaling of fragmentary
      giant pterosaur remains have been misled by distorted fossils or used
      inappropriate scaling techniques, indicating that 10-11 m wingspans and masses of
      200-250 kg are the most reliable upper estimates of known pterosaur size.

PMID- 21085625
TI  - Prioritizing emerging zoonoses in the Netherlands.
AB  - BACKGROUND: To support the development of early warning and surveillance systems
      of emerging zoonoses, we present a general method to prioritize pathogens using a
      quantitative, stochastic multi-criteria model, parameterized for the Netherlands.
      METHODOLOGY/PRINCIPAL FINDINGS: A risk score was based on seven criteria,
      reflecting assessments of the epidemiology and impact of these pathogens on
      society. Criteria were weighed, based on the preferences of a panel of judges
      with a background in infectious disease control. CONCLUSIONS/SIGNIFICANCE:
      Pathogens with the highest risk for the Netherlands included pathogens in the
      livestock reservoir with a high actual human disease burden (e.g. Campylobacter
      spp., Toxoplasma gondii, Coxiella burnetii) or a low current but higher historic
      burden (e.g. Mycobacterium bovis), rare zoonotic pathogens in domestic animals
      with severe disease manifestations in humans (e.g. BSE prion, Capnocytophaga
      canimorsus) as well as arthropod-borne and wildlife associated pathogens which
      may pose a severe risk in future (e.g. Japanese encephalitis virus and West-Nile
      virus). These agents are key targets for development of early warning and
      surveillance.

PMID- 21085626
TI  - Investigation of a genome wide association signal for obesity: synthetic
      association and haplotype analyses at the melanocortin 4 receptor gene locus.
AB  - BACKGROUND: Independent genome-wide association studies (GWAS) showed an
      obesogenic effect of two single nucleotide polymorphisms (SNP; rs12970134 and
      rs17782313) more than 150 kb downstream of the melanocortin 4 receptor gene
      (MC4R). It is unclear if the SNPs directly influence MC4R function or expression,
      or if the SNPs are on a haplotype that predisposes to obesity or includes
      functionally relevant genetic variation (synthetic association). As both exist,
      functionally relevant mutations and polymorphisms in the MC4R coding region and a
      robust association downstream of the gene, MC4R is an ideal model to explore
      synthetic association. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed a genomic
      region (364.9 kb) encompassing the MC4R in GWAS data of 424 obesity trios
      (extremely obese child/adolescent and both parents). SNP rs12970134 showed the
      lowest p-value (p = 0.004; relative risk for the obesity effect allele: 1.37);
      conditional analyses on this SNP revealed that 7 of 78 analyzed SNPs provided
      independent signals (p<=0.05). These 8 SNPs were used to derive two-marker
      haplotypes. The three best (according to p-value) haplotype combinations were
      chosen for confirmation in 363 independent obesity trios. The confirmed obesity
      effect haplotype includes SNPs 3' and 5' of the MC4R. Including MC4R coding
      variants in a joint model had almost no impact on the effect size estimators
      expected under synthetic association. CONCLUSIONS/SIGNIFICANCE: A haplotype
      reaching from a region 5' of the MC4R to a region at least 150 kb from the 3' end
      of the gene showed a stronger association to obesity than single SNPs. Synthetic
      association analyses revealed that MC4R coding variants had almost no impact on
      the association signal. Carriers of the haplotype should be enriched for relevant
      mutations outside the MC4R coding region and could thus be used for re-sequencing
      approaches. Our data also underscore the problems underlying the identification
      of relevant mutations depicted by GWAS derived SNPs.

PMID- 21085627
TI  - High sensitivity TSS prediction: estimates of locations where TSS cannot occur.
AB  - BACKGROUND: Although transcription in mammalian genomes can initiate from various
      genomic positions (e.g., 3'UTR, coding exons, etc.), most locations on genomes
      are not prone to transcription initiation. It is of practical and theoretical
      interest to be able to estimate such collections of non-TSS locations (NTLs). The
      identification of large portions of NTLs can contribute to better focusing the
      search for TSS locations and thus contribute to promoter and gene finding. It can
      help in the assessment of 5' completeness of expressed sequences, contribute to
      more successful experimental designs, as well as more accurate gene annotation.
      METHODOLOGY: Using comprehensive collections of Cap Analysis of Gene Expression
      (CAGE) and other transcript data from mouse and human genomes, we developed a
      methodology that allows us, by performing computational TSS prediction with very
      high sensitivity, to annotate, with a high accuracy in a strand specific manner,
      locations of mammalian genomes that are highly unlikely to harbor transcription
      start sites (TSSs). The properties of the immediate genomic neighborhood of
      98,682 accurately determined mouse and 113,814 human TSSs are used to determine
      features that distinguish genomic transcription initiation locations from those
      that are not likely to initiate transcription. In our algorithm we utilize
      various constraining properties of features identified in the upstream and
      downstream regions around TSSs, as well as statistical analyses of these
      surrounding regions. CONCLUSIONS: Our analysis of human chromosomes 4, 21 and 22
      estimates ~46%, ~41% and ~27% of these chromosomes, respectively, as being NTLs.
      This suggests that on average more than 40% of the human genome can be expected
      to be highly unlikely to initiate transcription. Our method represents the first
      one that utilizes high-sensitivity TSS prediction to identify, with high
      accuracy, large portions of mammalian genomes as NTLs. The server with our
      algorithm implemented is available at http://cbrc.kaust.edu.sa/ddm/.

PMID- 21085628
TI  - A coastal cline in sodium accumulation in Arabidopsis thaliana is driven by
      natural variation of the sodium transporter AtHKT1;1.
AB  - The genetic model plant Arabidopsis thaliana, like many plant species,
      experiences a range of edaphic conditions across its natural habitat. Such
      heterogeneity may drive local adaptation, though the molecular genetic basis
      remains elusive. Here, we describe a study in which we used genome-wide
      association mapping, genetic complementation, and gene expression studies to
      identify cis-regulatory expression level polymorphisms at the AtHKT1;1 locus,
      encoding a known sodium (Na(+)) transporter, as being a major factor controlling
      natural variation in leaf Na(+) accumulation capacity across the global A.
      thaliana population. A weak allele of AtHKT1;1 that drives elevated leaf Na(+) in
      this population has been previously linked to elevated salinity tolerance.
      Inspection of the geographical distribution of this allele revealed its
      significant enrichment in populations associated with the coast and saline soils
      in Europe. The fixation of this weak AtHKT1;1 allele in these populations is
      genetic evidence supporting local adaptation to these potentially saline impacted
      environments.

PMID- 21085629
TI  - Analysis of the 10q11 cancer risk locus implicates MSMB and NCOA4 in human
      prostate tumorigenesis.
AB  - Genome-wide association studies (GWAS) have established a variant, rs10993994, on
      chromosome 10q11 as being associated with prostate cancer risk. Since the variant
      is located outside of a protein-coding region, the target genes driving
      tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB
      and NCOA4, are strong candidates for mediating the effects of rs109939934. In a
      cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is
      associated with decreased expression of two MSMB isoforms in histologically
      normal and malignant prostate tissue. In addition, the risk allele is associated
      with increased expression of five NCOA4 isoforms in histologically normal
      prostate tissue only. No consistent association with either gene is observed in
      breast or colon tissue. In conjunction with these findings, suppression of MSMB
      expression or NCOA4 overexpression promotes anchorage-independent growth of
      prostate epithelial cells, but not growth of breast epithelial cells. These data
      suggest that germline variation at chromosome 10q11 contributes to prostate
      cancer risk by influencing expression of at least two genes. More broadly, the
      findings demonstrate that disease risk alleles may influence multiple genes, and
      associations between genotype and expression may only be observed in the context
      of specific tissue and disease states.

PMID- 21085630
TI  - Role of symbiotic auxotrophy in the Rhizobium-legume symbioses.
AB  - BACKGROUND: Rhizobium leguminosarum bv. viciae mutants unable to transport
      branched-chain amino acids via the two main amino acid ABC transport complexes
      AapJQMP and BraDEFGC produce a nitrogen starvation phenotype when inoculated on
      pea (Pisum sativum) plants [1], [2]. Bacteroids in indeterminate pea nodules have
      reduced abundance and a lower chromosome number. They reduce transcription of
      pathways for branched-chain amino acid biosynthesis and become dependent on their
      provision by the host. This has been called "symbiotic auxotrophy".
      METHODOLOGY/PRINCIPAL FINDINGS: A region important in solute specificity was
      identified in AapQ and changing P144D in this region reduced branched-chain amino
      acid transport to a very low rate. Strains carrying P144D were still fully
      effective for N(2) fixation on peas demonstrating that a low rate of branched
      amino acid transport in R. leguminosarum bv. viciae supports wild-type rates of
      nitrogen fixation. The importance of branched-chain amino acid transport was then
      examined in other legume-Rhizobium symbioses. An aap bra mutant of R.
      leguminosarum bv. phaseoli also showed nitrogen starvation symptoms when
      inoculated on French bean (Phaseolus vulgaris), a plant producing determinate
      nodules. The phenotype is different from that observed on pea and is accompanied
      by reduced nodule numbers and nitrogen fixation per nodule. However, an aap bra
      double mutant of Sinorhizobium meliloti 2011 showed no phenotype on alfalfa
      (Medicago sativa). CONCLUSIONS/SIGNIFICANCE: Symbiotic auxotrophy occurs in both
      determinate pea and indeterminate bean nodules demonstrating its importance for
      bacteroid formation and nodule function in legumes with different developmental
      programmes. However, only small quantities of branched chain amino acids are
      needed and symbiotic auxotrophy did not occur in the Sinorhizobium meliloti
      alfalfa symbiosis under the conditions measured. The contrasting symbiotic
      phenotypes of aap bra mutants inoculated on different legumes probably reflects
      altered timing of amino acid availability, development of symbiotic auxotrophy
      and nodule developmental programmes.

PMID- 21085631
TI  - Whole genome sequencing highlights genetic changes associated with laboratory
      domestication of C. elegans.
AB  - Defining the mutational landscape when individuals of a species grow separately
      and diverge over many generations can provide insights into trait evolution. A
      specific example of this involves studying changes associated with domestication
      where different lines of the same wild stock have been cultivated independently
      in different standard environments. Whole genome sequence comparison of such
      lines permits estimation of mutation rates, inference of genes' ancestral states
      and ancestry of existing strains, and correction of sequencing errors in genome
      databases. Here we study domestication of the C. elegans Bristol strain as a
      model, and report the genome sequence of LSJ1 (Bristol), a sibling of the
      standard C. elegans reference wild type N2 (Bristol). The LSJ1 and N2 lines were
      cultivated separately from shortly after the Bristol strain was isolated until
      methods to freeze C. elegans were developed. We find that during this time the
      two strains have accumulated 1208 genetic differences. We describe phenotypic
      variation between N2 and LSJ1 in the rate at which embryos develop, the rate of
      production of eggs, the maturity of eggs at laying, and feeding behavior, all the
      result of post-isolation changes. We infer the ancestral alleles in the original
      Bristol isolate and highlight 2038 likely sequencing errors in the original N2
      reference genome sequence. Many of these changes modify genome annotation. Our
      study provides a starting point to further investigate genotype-phenotype
      association and offers insights into the process of selection as a result of
      laboratory domestication.

PMID- 21085632
TI  - Replication and recombination factors contributing to recombination-dependent
      bypass of DNA lesions by template switch.
AB  - Damage tolerance mechanisms mediating damage-bypass and gap-filling are crucial
      for genome integrity. A major damage tolerance pathway involves recombination and
      is referred to as template switch. Template switch intermediates were visualized
      by 2D gel electrophoresis in the proximity of replication forks as X-shaped
      structures involving sister chromatid junctions. The homologous recombination
      factor Rad51 is required for the formation/stabilization of these intermediates,
      but its mode of action remains to be investigated. By using a combination of
      genetic and physical approaches, we show that the homologous recombination
      factors Rad55 and Rad57, but not Rad59, are required for the formation of
      template switch intermediates. The replication-proficient but recombination
      defective rfa1-t11 mutant is normal in triggering a checkpoint response following
      DNA damage but is impaired in X-structure formation. The Exo1 nuclease also has
      stimulatory roles in this process. The checkpoint kinase, Rad53, is required for
      X-molecule formation and phosphorylates Rad55 robustly in response to DNA damage.
      Although Rad55 phosphorylation is thought to activate recombinational repair
      under conditions of genotoxic stress, we find that Rad55 phosphomutants do not
      affect the efficiency of X-molecule formation. We also examined the DNA
      polymerase implicated in the DNA synthesis step of template switch. Deficiencies
      in translesion synthesis polymerases do not affect X-molecule formation, whereas
      DNA polymerase delta, required also for bulk DNA synthesis, plays an important
      role. Our data indicate that a subset of homologous recombination factors,
      together with DNA polymerase delta, promote the formation of template switch
      intermediates that are then preferentially dissolved by the action of the Sgs1
      helicase in association with the Top3 topoisomerase rather than resolved by
      Holliday Junction nucleases. Our results allow us to propose the choreography
      through which different players contribute to template switch in response to DNA
      damage and to distinguish this process from other recombination-mediated
      processes promoting DNA repair.

PMID- 21085633
TI  - A buoyancy-based screen of Drosophila larvae for fat-storage mutants reveals a
      role for Sir2 in coupling fat storage to nutrient availability.
AB  - Obesity has a strong genetic component, but few of the genes that predispose to
      obesity are known. Genetic screens in invertebrates have the potential to
      identify genes and pathways that regulate the levels of stored fat, many of which
      are likely to be conserved in humans. To facilitate such screens, we have
      developed a simple buoyancy-based screening method for identifying mutant
      Drosophila larvae with increased levels of stored fat. Using this approach, we
      have identified 66 genes that when mutated increase organismal fat levels. Among
      these was a sirtuin family member, Sir2. Sirtuins regulate the storage and
      metabolism of carbohydrates and lipids by deacetylating key regulatory proteins.
      However, since mammalian sirtuins function in many tissues in different ways, it
      has been difficult to define their role in energy homeostasis accurately under
      normal feeding conditions. We show that knockdown of Sir2 in the larval fat body
      results in increased fat levels. Moreover, using genetic mosaics, we demonstrate
      that Sir2 restricts fat accumulation in individual cells of the fat body in a
      cell-autonomous manner. Consistent with this function, changes in the expression
      of metabolic enzymes in Sir2 mutants point to a shift away from catabolism.
      Surprisingly, although Sir2 is typically upregulated under conditions of
      starvation, Sir2 mutant larvae survive better than wild type under conditions of
      amino-acid starvation as long as sugars are provided. Our findings point to a
      Sir2-mediated pathway that activates a catabolic response to amino-acid
      starvation irrespective of the sugar content of the diet.

PMID- 21085634
TI  - The transcriptional regulator Rok binds A+T-rich DNA and is involved in
      repression of a mobile genetic element in Bacillus subtilis.
AB  - The rok gene of Bacillus subtilis was identified as a negative regulator of
      competence development. It also controls expression of several genes not related
      to competence. We found that Rok binds to extended regions of the B. subtilis
      genome. These regions are characterized by a high A+T content and are known or
      believed to have been acquired by horizontal gene transfer. Some of the Rok
      binding regions are in known mobile genetic elements. A deletion of rok resulted
      in higher excision of one such element, ICEBs1, a conjugative transposon found
      integrated in the B. subtilis genome. When expressed in the Gram negative E.
      coli, Rok also associated with A+T-rich DNA and a conserved C-terminal region of
      Rok contributed to this association. Together with previous work, our findings
      indicate that Rok is a nucleoid associated protein that serves to help repress
      expression of A+T-rich genes, many of which appear to have been acquired by
      horizontal gene transfer. In these ways, Rok appears to be functionally analogous
      to H-NS, a nucleoid associated protein found in Gram negative bacteria and Lsr2
      of high G+C Mycobacteria.

PMID- 21085636
TI  - Beyond QTL cloning.

PMID- 21085635
TI  - Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of
      regulatory T-cells and improves immune function in subjects on HAART.
AB  - Although HAART suppresses HIV replication, it is often unable to restore immune
      homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in
      treated individuals. This is attributed to persistent virus expression in
      reservoirs and to cell activation. Of note, in CD4(+) T cells and monocyte
      macrophages of virologically-suppressed individuals, there is continued
      expression of multi-spliced transcripts encoding HIV regulatory proteins. Among
      them, Tat is essential for virus gene expression and replication, either in
      primary infection or for virus reactivation during HAART, when Tat is expressed,
      released extracellularly and exerts, on both the virus and the immune system,
      effects that contribute to disease maintenance. Here we report results of an ad
      hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed
      HAART-treated individuals enrolled in a phase II randomized open-label
      multicentric clinical trial of therapeutic immunization with Tat (ISS T-002).
      Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a
      parallel prospective observational study at the same sites (ISS OBS T-002),
      served for intergroup comparison. Immunization with Tat was safe, induced durable
      immune responses, and modified the pattern of CD4(+) and CD8(+) cellular
      activation (CD38 and HLA-DR) together with reduction of biochemical activation
      markers and persistent increases of regulatory T cells. This was accompanied by a
      progressive increment of CD4(+) T cells and B cells with reduction of CD8(+) T
      cells and NK cells, which were independent from the type of antiretroviral
      regimen. Increase in central and effector memory and reduction in terminally
      differentiated effector memory CD4(+) and CD8(+) T cells were accompanied by
      increases of CD4(+) and CD8(+) T cell responses against Env and recall antigens.
      Of note, more immune-compromised individuals experienced greater therapeutic
      effects. In contrast, these changes were opposite, absent or partial in the OBS
      population. These findings support the use of Tat immunization to intensify HAART
      efficacy and to restore immune homeostasis. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00751595.

PMID- 21085638
TI  - PLoS Computational Biology conference postcards from ISMB 2010.

PMID- 21085637
TI  - Robustness of circadian clocks to daylight fluctuations: hints from the
      picoeucaryote Ostreococcus tauri.
AB  - The development of systemic approaches in biology has put emphasis on identifying
      genetic modules whose behavior can be modeled accurately so as to gain insight
      into their structure and function. However, most gene circuits in a cell are
      under control of external signals and thus, quantitative agreement between
      experimental data and a mathematical model is difficult. Circadian biology has
      been one notable exception: quantitative models of the internal clock that
      orchestrates biological processes over the 24-hour diurnal cycle have been
      constructed for a few organisms, from cyanobacteria to plants and mammals. In
      most cases, a complex architecture with interlocked feedback loops has been
      evidenced. Here we present the first modeling results for the circadian clock of
      the green unicellular alga Ostreococcus tauri. Two plant-like clock genes have
      been shown to play a central role in the Ostreococcus clock. We find that their
      expression time profiles can be accurately reproduced by a minimal model of a two
      gene transcriptional feedback loop. Remarkably, best adjustment of data recorded
      under light/dark alternation is obtained when assuming that the oscillator is not
      coupled to the diurnal cycle. This suggests that coupling to light is confined to
      specific time intervals and has no dynamical effect when the oscillator is
      entrained by the diurnal cycle. This intriguing property may reflect a strategy
      to minimize the impact of fluctuations in daylight intensity on the core
      circadian oscillator, a type of perturbation that has been rarely considered when
      assessing the robustness of circadian clocks.

PMID- 21085639
TI  - Local gene regulation details a recognition code within the LacI transcriptional
      factor family.
AB  - The specific binding of regulatory proteins to DNA sequences exhibits no clear
      patterns of association between amino acids (AAs) and nucleotides (NTs). This
      complexity of protein-DNA interactions raises the question of whether a simple
      set of wide-coverage recognition rules can ever be identified. Here, we analyzed
      this issue using the extensive LacI family of transcriptional factors (TFs). We
      searched for recognition patterns by introducing a new approach to phylogenetic
      footprinting, based on the pervasive presence of local regulation in prokaryotic
      transcriptional networks. We identified a set of specificity correlations-
      determined by two AAs of the TFs and two NTs in the binding sites--that is
      conserved throughout a dominant subgroup within the family regardless of the
      evolutionary distance, and that act as a relatively consistent recognition code.
      The proposed rules are confirmed with data of previous experimental studies and
      by events of convergent evolution in the phylogenetic tree. The presence of a
      code emphasizes the stable structural context of the LacI family, while defining
      a precise blueprint to reprogram TF specificity with many practical applications.

PMID- 21085640
TI  - Functional genomics complements quantitative genetics in identifying disease-gene
      associations.
AB  - An ultimate goal of genetic research is to understand the connection between
      genotype and phenotype in order to improve the diagnosis and treatment of
      diseases. The quantitative genetics field has developed a suite of statistical
      methods to associate genetic loci with diseases and phenotypes, including
      quantitative trait loci (QTL) linkage mapping and genome-wide association studies
      (GWAS). However, each of these approaches have technical and biological
      shortcomings. For example, the amount of heritable variation explained by GWAS is
      often surprisingly small and the resolution of many QTL linkage mapping studies
      is poor. The predictive power and interpretation of QTL and GWAS results are
      consequently limited. In this study, we propose a complementary approach to
      quantitative genetics by interrogating the vast amount of high-throughput genomic
      data in model organisms to functionally associate genes with phenotypes and
      diseases. Our algorithm combines the genome-wide functional relationship network
      for the laboratory mouse and a state-of-the-art machine learning method. We
      demonstrate the superior accuracy of this algorithm through predicting genes
      associated with each of 1157 diverse phenotype ontology terms. Comparison between
      our prediction results and a meta-analysis of quantitative genetic studies
      reveals both overlapping candidates and distinct, accurate predictions uniquely
      identified by our approach. Focusing on bone mineral density (BMD), a phenotype
      related to osteoporotic fracture, we experimentally validated two of our novel
      predictions (not observed in any previous GWAS/QTL studies) and found significant
      bone density defects for both Timp2 and Abcg8 deficient mice. Our results suggest
      that the integration of functional genomics data into networks, which itself is
      informative of protein function and interactions, can successfully be utilized as
      a complementary approach to quantitative genetics to predict disease risks. All
      supplementary material is available at http://cbfg.jax.org/phenotype.

PMID- 21085642
TI  - Portrait of a pathogen: the Mycobacterium tuberculosis proteome in vivo.
AB  - BACKGROUND: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis
      (TB), is a facultative intracellular pathogen that can persist within the host.
      The bacteria are thought to be in a state of reduced replication and metabolism
      as part of the chronic lung infection. Many in vitro studies have dissected the
      hypothesized environment within the infected lung, defining the bacterial
      response to pH, starvation and hypoxia. While these experiments have afforded
      great insight, the picture remains incomplete. The only way to study the combined
      effects of these environmental factors and the mycobacterial response is to study
      the bacterial response in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We used the
      guinea pig model of tuberculosis to examine the bacterial proteome during the
      early and chronic stages of disease. Lungs were harvested thirty and ninety days
      after aerosol challenge with Mtb, and analyzed by liquid chromatography-mass
      spectrometry. To date, in vivo proteomics of the tubercle bacillus has not been
      described and this work has generated the first large-scale shotgun proteomic
      data set, comprising over 500 unique protein identifications. Cell wall and cell
      wall processes, and intermediary metabolism and respiration were the two major
      functional classes of proteins represented in the infected lung. These classes of
      proteins displayed the greatest heterogeneity indicating important biological
      processes for establishment of a productive bacterial infection and its
      persistence. Proteins necessary for adaptation throughout infection, such as
      nitrate/nitrite reduction were found at both time points. The PE-PPE protein
      class, while not well characterized, represented the third most abundant category
      and showed the most consistent expression during the infection.
      CONCLUSIONS/SIGNIFICANCE: Cumulatively, the results of this work may provide the
      basis for rational drug design - identifying numerous Mtb proteins, from
      essential kinases to products involved in metal regulation and cell wall
      remodeling, all present throughout the course of infection.

PMID- 21085643
TI  - Solving navigational uncertainty using grid cells on robots.
AB  - To successfully navigate their habitats, many mammals use a combination of two
      mechanisms, path integration and calibration using landmarks, which together
      enable them to estimate their location and orientation, or pose. In large natural
      environments, both these mechanisms are characterized by uncertainty: the path
      integration process is subject to the accumulation of error, while landmark
      calibration is limited by perceptual ambiguity. It remains unclear how animals
      form coherent spatial representations in the presence of such uncertainty.
      Navigation research using robots has determined that uncertainty can be
      effectively addressed by maintaining multiple probabilistic estimates of a
      robot's pose. Here we show how conjunctive grid cells in dorsocaudal medial
      entorhinal cortex (dMEC) may maintain multiple estimates of pose using a brain
      based robot navigation system known as RatSLAM. Based both on rodent spatially
      responsive cells and functional engineering principles, the cells at the core of
      the RatSLAM computational model have similar characteristics to rodent grid
      cells, which we demonstrate by replicating the seminal Moser experiments. We
      apply the RatSLAM model to a new experimental paradigm designed to examine the
      responses of a robot or animal in the presence of perceptual ambiguity. Our
      computational approach enables us to observe short-term population coding of
      multiple location hypotheses, a phenomenon which would not be easily observable
      in rodent recordings. We present behavioral and neural evidence demonstrating
      that the conjunctive grid cells maintain and propagate multiple estimates of
      pose, enabling the correct pose estimate to be resolved over time even without
      uniquely identifying cues. While recent research has focused on the grid-like
      firing characteristics, accuracy and representational capacity of grid cells, our
      results identify a possible critical and unique role for conjunctive grid cells
      in filtering sensory uncertainty. We anticipate our study to be a starting point
      for animal experiments that test navigation in perceptually ambiguous
      environments.

PMID- 21085641
TI  - The role of oligomerization and cooperative regulation in protein function: the
      case of tryptophan synthase.
AB  - The oligomerization/co-localization of protein complexes and their cooperative
      regulation in protein function is a key feature in many biological systems. The
      synergistic regulation in different subunits often enhances the functional
      properties of the multi-enzyme complex. The present study used molecular dynamics
      and Brownian dynamics simulations to study the effects of allostery,
      oligomerization and intermediate channeling on enhancing the protein function of
      tryptophan synthase (TRPS). TRPS uses a set of alpha/beta-dimeric units to
      catalyze the last two steps of L-tryptophan biosynthesis, and the rate is
      remarkably slower in the isolated monomers. Our work shows that without their
      binding partner, the isolated monomers are stable and more rigid. The substrates
      can form fairly stable interactions with the protein in both forms when the
      protein reaches the final ligand-bound conformations. Our simulations also
      revealed that the alpha/beta-dimeric unit stabilizes the substrate-protein
      conformation in the ligand binding process, which lowers the conformation
      transition barrier and helps the protein conformations shift from an
      open/inactive form to a closed/active form. Brownian dynamics simulations with a
      coarse-grained model illustrate how protein conformations affect substrate
      channeling. The results highlight the complex roles of protein oligomerization
      and the fine balance between rigidity and dynamics in protein function.

PMID- 21085644
TI  - A new integrated variable based on thermometry, actimetry and body position (TAP)
      to evaluate circadian system status in humans.
AB  - The disruption of the circadian system in humans has been associated with the
      development of chronic illnesses and the worsening of pre-existing pathologies.
      Therefore, the assessment of human circadian system function under free living
      conditions using non-invasive techniques needs further research. Traditionally,
      overt rhythms such as activity and body temperature have been analyzed
      separately; however, a comprehensive index could reduce individual recording
      artifacts. Thus, a new variable (TAP), based on the integrated analysis of three
      simultaneous recordings: skin wrist temperature (T), motor activity (A) and body
      position (P) has been developed. Furthermore, we also tested the reliability of a
      single numerical index, the Circadian Function Index (CFI), to determine the
      circadian robustness. An actimeter and a temperature sensor were placed on the
      arm and wrist of the non-dominant hand, respectively, of 49 healthy young
      volunteers for a period of one week. T, A and P values were normalized for each
      subject. A non-parametric analysis was applied to both TAP and the separate
      variables to calculate their interdaily stability, intradaily variability and
      relative amplitude, and these values were then used for the CFI calculation.
      Modeling analyses were performed in order to determine TAP and CFI reliability.
      Each variable (T, A, P or TAP) was independently correlated with rest-activity
      logs kept by the volunteers. The highest correlation (r= -0.993, p<0.0001), along
      with highest specificity (0.870), sensitivity (0.740) and accuracy (0.904), were
      obtained when rest-activity records were compared to TAP. Furthermore, the CFI
      proved to be very sensitive to changes in circadian robustness. Our results
      demonstrate that the integrated TAP variable and the CFI calculation are powerful
      methods to assess circadian system status, improving sensitivity, specificity and
      accuracy in differentiating activity from rest over the analysis of wrist
      temperature, body position or activity alone.

PMID- 21085646
TI  - Registry-based surveillance of influenza-associated hospitalisations during the
      2009 influenza pandemic in Denmark: the hidden burden on the young.
AB  - BACKGROUND: To follow the impact of the 2009 influenza pandemic in Denmark,
      influenza surveillance was extended with a system monitoring potentially
      influenza-associated hospitalisations. METHODOLOGY/PRINCIPAL FINDINGS: National
      administrative data from 2004-2010 from the automatic reporting of all hospital
      visits and admissions in Denmark (population 5.5 million) were used. In-patient
      hospitalisations linked to ICD-10 codes for potentially influenza-associated
      conditions (influenza, viral and bacterial pneumonia, respiratory distress, and
      febrile convulsion) were aggregated by week and age groups; <5 years, 5-24 years,
      25-64 years and >=65 years. Weekly numbers of influenza-associated
      hospitalisations were plotted to follow the course of the pandemic. We calculated
      the total numbers of influenza-associated hospitalisations in each influenza
      season (week 30 to week 15, the following year). Risk ratios of being admitted
      with an influenza-associated condition in this season (2009/2010) compared to the
      previous five seasons (2004/2005-2008/2009) were calculated using binary
      regression. During the pandemic season, influenza-associated hospitalisations
      peaked in week 47, 2009. The total number of influenza-associated
      hospitalisations was 38,273 compared to the median of previous seasons of 35,662
      (p = 0.28). The risk ratio of influenza-associated hospitalisations during the
      pandemic season compared to previous seasons was 1.63 (95%CI 1.49-1.78) for 5-24
      year-olds and ranged between 0.98 and 1.08 for the other three age groups.
      CONCLUSIONS: The 2009 pandemic influenza did not lead to an overall increase in
      the number of influenza-associated hospitalisations in Denmark in the 2009/2010
      season and could be managed within existing hospital capacity. However, there was
      a disproportionally large impact on the age group 5-24 years. The influenza
      associated hospitalisations during the 2009/2010 pandemic influenza season bore
      the signature features of historical pandemics: A skewed age-pattern and early
      out of season transmission.

PMID- 21085645
TI  - Vulnerabilities in the tau network and the role of ultrasensitive points in tau
      pathophysiology.
AB  - The multifactorial nature of disease motivates the use of systems-level analyses
      to understand their pathology. We used a systems biology approach to study tau
      aggregation, one of the hallmark features of Alzheimer's disease. A mathematical
      model was constructed to capture the current state of knowledge concerning tau's
      behavior and interactions in cells. The model was implemented in silico in the
      form of ordinary differential equations. The identifiability of the model was
      assessed and parameters were estimated to generate two cellular states: a
      population of solutions that corresponds to normal tau homeostasis and a
      population of solutions that displays aggregation-prone behavior. The model of
      normal tau homeostasis was robust to perturbations, and disturbances in multiple
      processes were required to achieve an aggregation-prone state. The aggregation
      prone state was ultrasensitive to perturbations in diverse subsets of networks.
      Tau aggregation requires that multiple cellular parameters are set coordinately
      to a set of values that drive pathological assembly of tau. This model provides a
      foundation on which to build and increase our understanding of the series of
      events that lead to tau aggregation and may ultimately be used to identify
      critical intervention points that can direct the cell away from tau aggregation
      to aid in the treatment of tau-mediated (or related) aggregation diseases
      including Alzheimer's.

PMID- 21085647
TI  - Preclinical deposition of pathological prion protein in muscle of experimentally
      infected primates.
AB  - Prion diseases are transmissible fatal neurodegenerative disorders affecting
      humans and animals. A central step in disease progression is the accumulation of
      a misfolded form (PrP(Sc)) of the host encoded prion protein (PrP(C)) in neuronal
      and non-neuronal tissues. The involvement of peripheral tissues in preclinical
      states increases the risk of accidental transmission. On the other hand,
      detection of PrP(Sc) in non-neuronal easy-accessible compartments such as muscle
      may offer a novel diagnostic tool. Primate models have proven invaluable to
      investigate prion diseases. We have studied the deposition of PrP(Sc) in muscle
      and central nervous system of rhesus monkeys challenged with sporadic Creutzfeldt
      Jakob disease (sCJD), variant CJD (vCJD) and bovine spongiform encephalopathy
      (BSE) in preclinical and clinical stage using biochemical and morphological
      methods. Here, we show the preclinical presence of PrP(Sc) in muscle and central
      nervous system of rhesus monkeys experimentally infected with vCJD.

PMID- 21085648
TI  - An evolutionary framework for association testing in resequencing studies.
AB  - Sequencing technologies are becoming cheap enough to apply to large numbers of
      study participants and promise to provide new insights into human phenotypes by
      bringing to light rare and previously unknown genetic variants. We develop a new
      framework for the analysis of sequence data that incorporates all of the major
      features of previously proposed approaches, including those focused on allele
      counts and allele burden, but is both more general and more powerful. We harness
      population genetic theory to provide prior information on effect sizes and to
      create a pooling strategy for information from rare variants. Our method, EMMPAT
      (Evolutionary Mixed Model for Pooled Association Testing), generates a single
      test per gene (substantially reducing multiple testing concerns), facilitates
      graphical summaries, and improves the interpretation of results by allowing
      calculation of attributable variance. Simulations show that, relative to
      previously used approaches, our method increases the power to detect genes that
      affect phenotype when natural selection has kept alleles with large effect sizes
      rare. We demonstrate our approach on a population-based re-sequencing study of
      association between serum triglycerides and variation in ANGPTL4.

PMID- 21085649
TI  - Metabolic footprint of diabetes: a multiplatform metabolomics study in an
      epidemiological setting.
AB  - BACKGROUND: Metabolomics is the rapidly evolving field of the comprehensive
      measurement of ideally all endogenous metabolites in a biological fluid. However,
      no single analytic technique covers the entire spectrum of the human metabolome.
      Here we present results from a multiplatform study, in which we investigate what
      kind of results can presently be obtained in the field of diabetes research when
      combining metabolomics data collected on a complementary set of analytical
      platforms in the framework of an epidemiological study. METHODOLOGY/PRINCIPAL
      FINDINGS: 40 individuals with self-reported diabetes and 60 controls (male, over
      54 years) were randomly selected from the participants of the population-based
      KORA (Cooperative Health Research in the Region of Augsburg) study, representing
      an extensively phenotyped sample of the general German population. Concentrations
      of over 420 unique small molecules were determined in overnight-fasting blood
      using three different techniques, covering nuclear magnetic resonance and tandem
      mass spectrometry. Known biomarkers of diabetes could be replicated by this
      multiple metabolomic platform approach, including sugar metabolites (1,5
      anhydroglucoitol), ketone bodies (3-hydroxybutyrate), and branched chain amino
      acids. In some cases, diabetes-related medication can be detected (pioglitazone,
      salicylic acid). CONCLUSIONS/SIGNIFICANCE: Our study depicts the promising
      potential of metabolomics in diabetes research by identification of a series of
      known and also novel, deregulated metabolites that associate with diabetes. Key
      observations include perturbations of metabolic pathways linked to kidney
      dysfunction (3-indoxyl sulfate), lipid metabolism (glycerophospholipids, free
      fatty acids), and interaction with the gut microflora (bile acids). Our study
      suggests that metabolic markers hold the potential to detect diabetes-related
      complications already under sub-clinical conditions in the general population.

PMID- 21085650
TI  - Thermodynamic additivity of sequence variations: an algorithm for creating high
      affinity peptides without large libraries or structural information.
AB  - BACKGROUND: There is a significant need for affinity reagents with high target
      affinity/specificity that can be developed rapidly and inexpensively. Existing
      affinity reagent development approaches, including protein mutagenesis, directed
      evolution, and fragment-based design utilize large libraries and/or require
      structural information thereby adding time and expense. Until now, no systematic
      approach to affinity reagent development existed that could produce nanomolar
      affinity from small chemically synthesized peptide libraries without the aid of
      structural information. METHODOLOGY/PRINCIPAL FINDINGS: Based on the principle of
      additivity, we have developed an algorithm for generating high affinity peptide
      ligands. In this algorithm, point-variations in a lead sequence are screened and
      combined in a systematic manner to achieve additive binding energies. To
      demonstrate this approach, low-affinity lead peptides for multiple protein
      targets were identified from sparse random sequence space and optimized to high
      affinity in just two chemical steps. In one example, a TNF-alpha binding peptide
      with K(d) = 90 nM and high target specificity was generated. The changes in
      binding energy associated with each variation were generally additive upon
      combining variations, validating the basis of the algorithm. Interestingly,
      cooperativity between point-variations was not observed, and in a few specific
      cases, combinations were less than energetically additive.
      CONCLUSIONS/SIGNIFICANCE: By using this additivity algorithm, peptide ligands
      with high affinity for protein targets were generated. With this algorithm, one
      of the highest affinity TNF-alpha binding peptides reported to date was produced.
      Most importantly, high affinity was achieved from small, chemically-synthesized
      libraries without the need for structural information at any time during the
      process. This is significantly different than protein mutagenesis, directed
      evolution, or fragment-based design approaches, which rely on large libraries
      and/or structural guidance. With this algorithm, high affinity/specificity
      peptide ligands can be developed rapidly, inexpensively, and in an entirely
      chemical manner.

PMID- 21085652
TI  - Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR
      ligand.
AB  - Activation of hepatic stellate cells (HSCs) plays an important role in the
      development of cirrhosis through the increased production of collagen and the
      enhanced contractile response to vasoactive mediators such as endothelin-1 (ET
      1). The farnesoid X receptor (FXR) is a member of the nuclear receptor
      superfamily that is highly expressed in liver, kidneys, adrenals, and intestine.
      FXR is also expressed in HSCs and activation of FXR in HSCs is associated with
      significant decreases in collagen production. However, little is known about the
      roles of FXR in the regulation of contraction of HSCs. We report in this study
      that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist,
      significantly inhibited the HSC transdifferentiation, which was associated with
      an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells
      also showed reduced contractile response to ET-1 in comparison to HSCs without
      GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1
      mediated contraction in fully activated HSCs. To elucidate the potential
      mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK
      pathway in activated HSCs. Our studies unveiled a new mechanism that might
      contribute to the anti-cirrhotic effects of FXR ligands.

PMID- 21085651
TI  - A role for the retinoblastoma protein as a regulator of mouse osteoblast cell
      adhesion: implications for osteogenesis and osteosarcoma formation.
AB  - The retinoblastoma protein (pRb) is a cell cycle regulator inactivated in most
      human cancers. Loss of pRb function results from mutations in the gene coding for
      pRb or for any of its upstream regulators. Although pRb is predominantly known as
      a cell cycle repressor, our data point to additional pRb functions in cell
      adhesion. Our data show that pRb regulates the expression of a wide repertoire of
      cell adhesion genes and regulates the assembly of the adherens junctions required
      for cell adhesion. We conducted our studies in osteoblasts, which depend on both
      pRb and on cell-to-cell contacts for their differentiation and function. We
      generated knockout mice in which the RB gene was excised specifically in
      osteoblasts using the cre-lox P system and found that osteoblasts from pRb
      knockout mice did not assemble adherens junction at their membranes. pRb
      depletion in wild type osteoblasts using RNAi also disrupted adherens junctions.
      Microarrays comparing pRb-expressing and pRb-deficient osteoblasts showed that
      pRb controls the expression of a number of cell adhesion genes, including
      cadherins. Furthermore, pRb knockout mice showed bone abnormalities consistent
      with osteoblast adhesion defects. We also found that pRb controls the function of
      merlin, a well-known regulator of adherens junction assembly, by repressing Rac1
      and its effector Pak1. Using qRT-PCR, immunoblots, co-immunoprecipitation assays,
      and immunofluorescent labeling, we observed that pRb loss resulted in Rac1 and
      Pak1 overexpression concomitant with merlin inactivation by Pak1, merlin
      detachment from the membrane, and adherens junction loss. Our data support a pRb
      function in cell adhesion while elucidating the mechanism for this function. Our
      work suggests that in some tumor types pRb inactivation results in both a loss of
      cell cycle control that promotes initial tumor growth as well as in a loss of
      cell-to-cell contacts, which contributes to later stages of metastasis.

PMID- 21085653
TI  - Molecular characterization of the mouse superior lateral parabrachial nucleus
      through expression of the transcription factor Runx1.
AB  - BACKGROUND: The ability to precisely identify separate neuronal populations is
      essential to the understanding of the development and function of different brain
      structures. This necessity is particularly evident in regions such as the
      brainstem, where the anatomy is quite complex and little is known about the
      identity, origin, and function of a number of distinct nuclei due to the lack of
      specific cellular markers. In this regard, the gene encoding the transcription
      factor Runx1 has emerged as a specific marker of restricted neuronal populations
      in the murine central and peripheral nervous systems. The aim of this study was
      to precisely characterize the expression of Runx1 in the developing and postnatal
      mouse brainstem. METHODS AND PRINCIPAL FINDINGS: Anatomical and
      immunohistochemical studies were used to characterize mouse Runx1 expression in
      the brainstem. It is shown here that Runx1 is expressed in a restricted
      population of neurons located in the dorsolateral rostral hindbrain. These
      neurons define a structure that is ventromedial to the dorsal nucleus of the
      lateral lemniscus, dorsocaudal to the medial paralemniscal nucleus and rostral to
      the cerebellum. Runx1 expression in these cells is first observed at
      approximately gestational day 12.5, persists into the adult brain, and is lost in
      knockout mice lacking the transcription factor Atoh1, an important regulator of
      the development of neuronal lineages of the rhombic lip. Runx1-expressing neurons
      in the rostral hindbrain produce cholecystokinin and also co-express members of
      the Groucho/Transducin-like Enhancer of split protein family. CONCLUSION: Based
      on the anatomical and molecular characteristics of the Runx1-expressing cells in
      the rostral hindbrain, we propose that Runx1 expression in this region of the
      mouse brain defines the superior lateral parabrachial nucleus.

PMID- 21085654
TI  - Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of
      spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood
      characterized by marked muscle weakness. To investigate mechanisms underlying
      motor impairment in SMA, we examined the spinal and neuromuscular circuitry
      governing hindlimb ambulatory behavior in SMA model mice (SMNDelta7). In the
      neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs)
      in hindlimb muscles of SMNDelta7 mice remained fully innervated at the disease
      end stage and were capable of eliciting muscle contraction, despite a modest
      reduction in quantal content. In the spinal circuitry, we observed a ~28% loss of
      synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5,
      and a significant reduction in proprioceptive sensory neurons, which may
      contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)
      positive synapses onto SMNDelta7 motoneurons. In addition, there was an increase
      in the association of activated microglia with SMNDelta7 motoneurons. Together,
      our results present a novel concept that synaptic defects occur at multiple
      levels of the spinal and neuromuscular circuitry in SMNDelta7 mice, and that
      proprioceptive spinal synapses could be a potential target for SMA therapy.

PMID- 21085655
TI  - Flight modes in migrating European bee-eaters: heart rate may indicate low
      metabolic rate during soaring and gliding.
AB  - BACKGROUND: Many avian species soar and glide over land. Evidence from large
      birds (m(b)>0.9 kg) suggests that soaring-gliding is considerably cheaper in
      terms of energy than flapping flight, and costs about two to three times the
      basal metabolic rate (BMR). Yet, soaring-gliding is considered unfavorable for
      small birds because migration speed in small birds during soaring-gliding is
      believed to be lower than that of flapping flight. Nevertheless, several small
      bird species routinely soar and glide. METHODOLOGY/PRINCIPAL FINDINGS: To
      estimate the energetic cost of soaring-gliding flight in small birds, we measured
      heart beat frequencies of free-ranging migrating European bee-eaters (Merops
      apiaster, m(b)~55 g) using radio telemetry, and established the relationship
      between heart beat frequency and metabolic rate (by indirect calorimetry) in the
      laboratory. Heart beat frequency during sustained soaring-gliding was 2.2 to 2.5
      times lower than during flapping flight, but similar to, and not significantly
      different from, that measured in resting birds. We estimated that soaring-gliding
      metabolic rate of European bee-eaters is about twice their basal metabolic rate
      (BMR), which is similar to the value estimated in the black-browed albatross
      Thalassarche (previously Diomedea) melanophrys, m(b)~4 kg). We found that soaring
      gliding migration speed is not significantly different from flapping migration
      speed. CONCLUSIONS/SIGNIFICANCE: We found no evidence that soaring-gliding speed
      is slower than flapping flight in bee-eaters, contradicting earlier estimates
      that implied a migration speed penalty for using soaring-gliding rather than
      flapping flight. Moreover, we suggest that small birds soar and glide during
      migration, breeding, dispersal, and other stages in their annual cycle because it
      may entail a low energy cost of transport. We propose that the energy cost of
      soaring-gliding may be proportional to BMR regardless of bird size, as
      theoretically deduced by earlier studies.

PMID- 21085656
TI  - Mutations in the polycomb group gene polyhomeotic lead to epithelial instability
      in both the ovary and wing imaginal disc in Drosophila.
AB  - BACKGROUND: Most human cancers originate from epithelial tissues and cell
      polarity and adhesion defects can lead to metastasis. The Polycomb-Group of
      chromatin factors were first characterized in Drosophila as repressors of
      homeotic genes during development, while studies in mammals indicate a conserved
      role in body plan organization, as well as an implication in other processes such
      as stem cell maintenance, cell proliferation, and tumorigenesis. We have analyzed
      the function of the Drosophila Polycomb-Group gene polyhomeotic in epithelial
      cells of two different organs, the ovary and the wing imaginal disc. RESULTS:
      Clonal analysis of loss and gain of function of polyhomeotic resulted in
      segregation between mutant and wild-type cells in both the follicular and wing
      imaginal disc epithelia, without excessive cell proliferation. Both basal and
      apical expulsion of mutant cells was observed, the former characterized by
      specific reorganization of cell adhesion and polarity proteins, the latter by
      complete cytoplasmic diffusion of these proteins. Among several candidate target
      genes tested, only the homeotic gene Abdominal-B was a target of PH in both
      ovarian and wing disc cells. Although overexpression of Abdominal-B was
      sufficient to cause cell segregation in the wing disc, epistatic analysis
      indicated that the presence of Abdominal-B is not necessary for expulsion of
      polyhomeotic mutant epithelial cells suggesting that additional polyhomeotic
      targets are implicated in this phenomenon. CONCLUSION: Our results indicate that
      polyhomeotic mutations have a direct effect on epithelial integrity that can be
      uncoupled from overproliferation. We show that cells in an epithelium expressing
      different levels of polyhomeotic sort out indicating differential adhesive
      properties between the cell populations. Interestingly, we found distinct
      modalities between apical and basal expulsion of ph mutant cells and further
      studies of this phenomenon should allow parallels to be made with the modified
      adhesive and polarity properties of different types of epithelial tumors.

PMID- 21085657
TI  - Human stem cell-derived neurons: a system to study human tau function and
      dysfunction.
AB  - BACKGROUND: Intracellular filamentous deposits containing microtubule-associated
      protein tau constitute a defining characteristic of many neurodegenerative
      disorders. Current experimental models to study tau pathology in vitro do not
      usually recapitulate the tau expression pattern characteristic of adult human
      brain. In this study, we have investigated whether human embryonic stem cell
      derived neurons could be a good model to study human tau distribution, function
      and dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR,
      immunohistochemistry, western blotting and cell transfections we have
      investigated whether all 6 adult human brain tau isoforms are expressed in
      neurons derived from human embryonic and fetal stem cells and whether 4 repeat
      tau over-expression alone, or with the F3 tau repeat fragment, (amino acid 258
      380 of the 2N4R tau isoform with the DeltaK280 mutation) affects tau
      distribution. We found that the shortest 3 repeat tau isoform, similarly to human
      brain, is the first to be expressed during neuronal differentiation while the
      other 5 tau isoforms are expressed later. Over expression of tau with 4 repeats
      affects tau cellular distribution and the short tau F3 fragment appears to
      increase tau phosphorylation but this effect does not appear to be toxic for the
      cell. CONCLUSIONS: Our results indicate that human embryonic stem cell-derived
      neurons express all 6 tau isoforms and are a good model in which to study tau
      physiology and pathology.

PMID- 21085659
TI  - Urban scaling and its deviations: revealing the structure of wealth, innovation
      and crime across cities.
AB  - With urban population increasing dramatically worldwide, cities are playing an
      increasingly critical role in human societies and the sustainability of the
      planet. An obstacle to effective policy is the lack of meaningful urban metrics
      based on a quantitative understanding of cities. Typically, linear per capita
      indicators are used to characterize and rank cities. However, these implicitly
      ignore the fundamental role of nonlinear agglomeration integral to the life
      history of cities. As such, per capita indicators conflate general nonlinear
      effects, common to all cities, with local dynamics, specific to each city,
      failing to provide direct measures of the impact of local events and policy.
      Agglomeration nonlinearities are explicitly manifested by the superlinear power
      law scaling of most urban socioeconomic indicators with population size, all with
      similar exponents (1.15). As a result larger cities are disproportionally the
      centers of innovation, wealth and crime, all to approximately the same degree. We
      use these general urban laws to develop new urban metrics that disentangle
      dynamics at different scales and provide true measures of local urban
      performance. New rankings of cities and a novel and simpler perspective on urban
      systems emerge. We find that local urban dynamics display long-term memory, so
      cities under or outperforming their size expectation maintain such (dis)advantage
      for decades. Spatiotemporal correlation analyses reveal a novel functional
      taxonomy of U.S. metropolitan areas that is generally not organized
      geographically but based instead on common local economic models, innovation
      strategies and patterns of crime.

PMID- 21085658
TI  - Phosphoproteomics-based modeling defines the regulatory mechanism underlying
      aberrant EGFR signaling.
AB  - BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR) results in a
      discordant cell signaling, leading to the development of various diseases.
      However, the mechanism underlying the alteration of downstream signaling due to
      such mutation has not yet been completely understood at the system level. Here,
      we report a phosphoproteomics-based methodology for characterizing the regulatory
      mechanism underlying aberrant EGFR signaling using computational network
      modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the
      mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of
      EGFR, revealed network-wide effects of the mutation on EGF signaling in a time
      resolved manner. Computational modeling based on the temporal activation profiles
      enabled us to not only rediscover already-known protein interactions with Y992
      and internalization property of mutated EGFR but also further gain model-driven
      insights into the effect of cellular content and the regulation of EGFR
      degradation. Our kinetic model also suggested critical reactions facilitating the
      reconstruction of the diverse effects of the mutation on phosphoproteome
      dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a
      mechanistic description of the disorders of mutated EGFR signaling networks,
      which could facilitate the development of a systematic strategy toward
      controlling disease-related cell signaling.

PMID- 21085660
TI  - Levodopa-induced dyskinesia is associated with increased thyrotropin releasing
      hormone in the dorsal striatum of hemi-parkinsonian rats.
AB  - BACKGROUND: Dyskinesias associated with involuntary movements and painful muscle
      contractions are a common and severe complication of standard levodopa (L-DOPA, L
      3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic
      neuroplasticity leading to hyper-responsive dopamine receptor signaling in the
      sensorimotor striatum is thought to underlie this currently untreatable
      condition. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative real-time polymerase
      chain reaction (PCR) was employed to evaluate the molecular changes associated
      with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we
      determined that thyrotropin releasing hormone (TRH) was greatly increased in the
      dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal
      movements in response to L-DOPA therapy, relative to the levels measured in the
      contralateral non-dopamine-depleted striatum, and in the striatum of non
      dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels
      were almost absent in the dopamine-depleted striatum of control rats that did not
      develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was
      dramatically up-regulated in the striatum, particularly in the sensorimotor
      striatum. This up-regulation of TRH peptide affected striatal medium spiny
      neurons of both the direct and indirect pathways, as well as neurons in
      striosomes. CONCLUSIONS/SIGNIFICANCE: TRH is not known to be a key striatal
      neuromodulator, but intrastriatal injection of TRH in experimental animals can
      induce abnormal movements, apparently through increasing dopamine release. Our
      finding of a dramatic and selective up-regulation of TRH expression in the
      sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory
      mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper
      responsivity in Parkinson's disease.

PMID- 21085661
TI  - Key steps in developing a cognitive vaccine against traumatic flashbacks:
      visuospatial Tetris versus verbal Pub Quiz.
AB  - BACKGROUND: Flashbacks (intrusive memories of a traumatic event) are the hallmark
      feature of Post Traumatic Stress Disorder, however preventative interventions are
      lacking. Tetris may offer a 'cognitive vaccine' [1] against flashback development
      after trauma exposure. We previously reported that playing the computer game
      Tetris soon after viewing traumatic material reduced flashbacks compared to no
      task [1]. However, two criticisms need to be addressed for clinical translation:
      (1) Would all games have this effect via distraction/enjoyment, or might some
      games even be harmful? (2) Would effects be found if administered several hours
      post-trauma? Accordingly, we tested Tetris versus an alternative computer game-
      Pub Quiz--which we hypothesized not to be helpful (Experiments 1 and 2), and
      extended the intervention interval to 4 hours (Experiment 2).
      METHODOLOGY/PRINCIPAL FINDINGS: The trauma film paradigm was used as an
      experimental analog for flashback development in healthy volunteers. In both
      experiments, participants viewed traumatic film footage of death and injury
      before completing one of the following: (1) no-task control condition (2) Tetris
      or (3) Pub Quiz. Flashbacks were monitored for 1 week. Experiment 1: 30 min after
      the traumatic film, playing Tetris led to a significant reduction in flashbacks
      compared to no-task control, whereas Pub Quiz led to a significant increase in
      flashbacks. Experiment 2: 4 hours post-film, playing Tetris led to a significant
      reduction in flashbacks compared to no-task control, whereas Pub Quiz did not.
      CONCLUSIONS/SIGNIFICANCE: First, computer games can have differential effects
      post-trauma, as predicted by a cognitive science formulation of trauma memory. In
      both Experiments, playing Tetris post-trauma film reduced flashbacks. Pub Quiz
      did not have this effect, even increasing flashbacks in Experiment 1. Thus not
      all computer games are beneficial or merely distracting post-trauma - some may be
      harmful. Second, the beneficial effects of Tetris are retained at 4 hours post
      trauma. Clinically, this delivers a feasible time-window to administer a post
      trauma "cognitive vaccine".

PMID- 21085662
TI  - Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling.
AB  - Type I interferons (IFNs) function as the first line of defense against viral
      infections by modulating cell growth, establishing an antiviral state and
      influencing the activation of various immune cells. Viruses such as influenza
      have developed mechanisms to evade this defense mechanism and during infection
      with influenza A viruses, the non-structural protein 1 (NS1) encoded by the virus
      genome suppresses induction of IFNs-alpha/beta. Here we show that expression of
      avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces
      IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the
      nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1
      , STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling
      by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of
      expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated
      inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non
      tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1
      virus infection of human monocyte-derived macrophages led to inhibition of both
      ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation
      of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo
      human lung tissues with IFN-alpha results in the up-regulation of a number of IFN
      stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data
      suggest that NS1 can directly interfere with IFN signaling to enhance viral
      replication, but that treatment with IFN can nevertheless override these
      inhibitory effects to block H5N1 and H1N1 virus infections.

PMID- 21085663
TI  - Amyloid-beta oligomer specificity mediated by the IgM isotype--implications for a
      specific protective mechanism exerted by endogenous auto-antibodies.
AB  - BACKGROUND: Alzheimers disease (AD) has been strongly linked to an anomalous self
      assembly of the amyloid-beta peptide (Abeta). The correlation between clinical
      symptoms of AD and Abeta depositions is, however, weak. Instead small and soluble
      Abeta oligomers are suggested to exert the major pathological effects. In strong
      support of this notion, immunological targeting of Abeta oligomers in AD mice
      models shows that memory impairments can be restored without affecting the total
      burden of Abeta deposits. Consequently a specific immunological targeting of
      Abeta oligomers is of high therapeutic interest. METHODOLOGY/PRINCIPAL FINDINGS:
      Previously the generation of conformational-dependent oligomer specific anti
      Abeta antibodies has been described. However, to avoid the difficult task of
      identifying a molecular architecture only present on oligomers, we have focused
      on a more general approach based on the hypothesis that all oligomers expose
      multiple identical epitopes and therefore would have an increased binding to a
      multivalent receptor. Using the polyvalent IgM immunoglobulin we have developed a
      monoclonal anti-Abeta antibody (OMAB). OMAB only demonstrates a weak interaction
      with Abeta monomers and dimers having fast on and off-rate kinetics. However, as
      an effect of avidity, its interaction with Abeta-oligomers results in a strong
      complex with an exceptionally slow off-rate. Through this mechanism a selectivity
      towards Abeta oligomers is acquired and OMAB fully inhibits the cytotoxic effect
      exerted by Abeta(1-42) at highly substoichiometric ratios. Anti-Abeta auto
      antibodies of IgM isotype are frequently present in the sera of humans. Through a
      screen of endogenous anti-Abeta IgM auto-antibodies from a group of healthy
      individuals we show that all displays a preference for oligomeric Abeta.
      CONCLUSIONS/SIGNIFICANCE: Taken together we provide a simple and general
      mechanism for targeting of oligomers without the requirement of conformational
      dependent epitopes. In addition, our results suggest that IgM anti-Abeta auto
      antibodies may exert a more specific protective mechanism in vivo than previously
      anticipated.

PMID- 21085664
TI  - Inhibiting alpha-synuclein oligomerization by stable cell-penetrating beta
      synuclein fragments recovers phenotype of Parkinson's disease model flies.
AB  - The intracellular oligomerization of alpha-synuclein is associated with
      Parkinson's disease and appears to be an important target for disease-modifying
      treatment. Yet, to date, there is no specific inhibitor for this aggregation
      process. Using unbiased systematic peptide array analysis, we identified
      molecular interaction domains within the beta-synuclein polypeptide that
      specifically binds alpha-synuclein. Adding such peptide fragments to alpha
      synuclein significantly reduced both amyloid fibrils and soluble oligomer
      formation in vitro. A retro-inverso analogue of the best peptide inhibitor was
      designed to develop the identified molecular recognition module into a drug
      candidate. While this peptide shows indistinguishable activity as compared to the
      native peptide, it is stable in mouse serum and penetrates alpha-synuclein over
      expressing cells. The interaction interface between the D-amino acid peptide and
      alpha-synuclein was mapped by Nuclear Magnetic Resonance spectroscopy. Finally,
      administering the retro-inverso peptide to a Drosophila model expressing mutant
      A53T alpha-synuclein in the nervous system, resulted in a significant recovery of
      the behavioral abnormalities of the treated flies and in a significant reduction
      in alpha-synuclein accumulation in the brains of the flies. The engineered retro
      inverso peptide can serve as a lead for developing a novel class of therapeutic
      agents to treat Parkinson's disease.

PMID- 21085666
TI  - Phenotypic complexity, measurement bias, and poor phenotypic resolution
      contribute to the missing heritability problem in genetic association studies.
AB  - BACKGROUND: The variance explained by genetic variants as identified in (genome
      wide) genetic association studies is typically small compared to family-based
      heritability estimates. Explanations of this 'missing heritability' have been
      mainly genetic, such as genetic heterogeneity and complex (epi-)genetic
      mechanisms. METHODOLOGY: We used comprehensive simulation studies to show that
      three phenotypic measurement issues also provide viable explanations of the
      missing heritability: phenotypic complexity, measurement bias, and phenotypic
      resolution. We identify the circumstances in which the use of phenotypic sum
      scores and the presence of measurement bias lower the power to detect genetic
      variants. In addition, we show how the differential resolution of psychometric
      instruments (i.e., whether the instrument includes items that resolve individual
      differences in the normal range or in the clinical range of a phenotype) affects
      the power to detect genetic variants. CONCLUSION: We conclude that careful
      phenotypic data modelling can improve the genetic signal, and thus the
      statistical power to identify genetic variants by 20-99%.

PMID- 21085665
TI  - Cyclophilin B interacts with sodium-potassium ATPase and is required for pump
      activity in proximal tubule cells of the kidney.
AB  - Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are
      responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning
      several membrane proteins. Those functions are inhibited upon CsA binding. Albeit
      its great benefits as immunosuppressant, the use of CsA has been limited by
      undesirable nephrotoxic effects, including sodium retention, hypertension,
      hyperkalemia, interstial fibrosis and progressive renal failure in transplant
      recipients. In this report, we focused on the identification of novel CypB
      interacting proteins to understand the role of CypB in kidney function and, in
      turn, to gain further insight into the molecular mechanisms of CsA-induced
      toxicity. By means of yeast two-hybrid screens with human kidney cDNA, we
      discovered a novel interaction between CypB and the membrane Na/K-ATPase beta1
      subunit protein (Na/K-beta1) that was confirmed by pull-down, co
      immunoprecipitation and confocal microscopy, in proximal tubule-derived HK-2
      cells. The Na/K-ATPase pump, a key plasma membrane transporter, is responsible
      for maintenance of electrical Na+ and K+ gradients across the membrane. We showed
      that CypB silencing produced similar effects on Na/K-ATPase activity than CsA
      treatment in HK-2 cells. It was also observed an enrichment of both alpha and
      beta subunits in the ER, what suggested a possible failure on the maturation and
      routing of the pump from this compartment towards the plasma membrane. These data
      indicate that CypB through its interaction with Na/K-beta1 might regulate
      maturation and trafficking of the pump through the secretory pathway, offering
      new insights into the relationship between cyclophilins and the nephrotoxic
      effects of CsA.

PMID- 21085667
TI  - Cue-reactors: individual differences in cue-induced craving after food or smoking
      abstinence.
AB  - BACKGROUND: Pavlovian conditioning plays a critical role in both drug addiction
      and binge eating. Recent animal research suggests that certain individuals are
      highly sensitive to conditioned cues, whether they signal food or drugs. Are
      certain humans also more reactive to both food and drug cues? METHODS: We
      examined cue-induced craving for both cigarettes and food, in the same
      individuals (n = 15 adult smokers). Subjects viewed smoking-related or food
      related images after abstaining from either smoking or eating. RESULTS: Certain
      individuals reported strong cue-induced craving after both smoking and food cues.
      That is, subjects who reported strong cue-induced craving for cigarettes also
      rated stronger cue-induced food craving. CONCLUSIONS: In humans, like in
      nonhumans, there may be a "cue-reactive" phenotype, consisting of individuals who
      are highly sensitive to conditioned stimuli. This finding extends recent reports
      from nonhuman studies. Further understanding this subgroup of smokers may allow
      clinicians to individually tailor therapies for smoking cessation.

PMID- 21085668
TI  - Quantitative assessment of the sensitivity of various commercial reverse
      transcriptases based on armored HIV RNA.
AB  - BACKGROUND: The in-vitro reverse transcription of RNA to its complementary DNA,
      catalyzed by the enzyme reverse transcriptase, is the most fundamental step in
      the quantitative RNA detection in genomic studies. As such, this step should be
      as analytically sensitive, efficient and reproducible as possible, especially
      when dealing with degraded or low copy RNA samples. While there are many reverse
      transcriptases in the market, all claiming to be highly sensitive, there is need
      for a systematic independent comparison of their applicability in quantification
      of rare RNA transcripts or low copy RNA, such as those obtained from archival
      tissues. METHODOLOGY/PRINCIPAL FINDINGS: We performed RT-qPCR to assess the
      sensitivity and reproducibility of 11 commercially available reverse
      transcriptases in cDNA synthesis from low copy number RNA levels. As target RNA,
      we used a serially known number of Armored HIV RNA molecules, and observed that 9
      enzymes we tested were consistently sensitive to ~1,000 copies, seven of which
      were sensitive to ~100 copies, while only 5 were sensitive to ~10 RNA template
      copies across all replicates tested. Despite their demonstrated sensitivity,
      these five best performing enzymes (Accuscript, HIV-RT, M-MLV, Superscript III
      and Thermoscript) showed considerable variation in their reproducibility as well
      as their overall amplification efficiency. Accuscript and Superscript III were
      the most sensitive and consistent within runs, with Accuscript and Superscript II
      ranking as the most reproducible enzymes between assays.
      CONCLUSIONS/SIGNIFICANCE: We therefore recommend the use of Accuscript or
      Superscript III when dealing with low copy number RNA levels, and suggest
      purification of the RT reactions prior to downstream applications (eg qPCR) to
      augment detection. Although the results presented in this study were based on a
      viral RNA surrogate, and applied to nucleic acid lysates derived from archival
      formalin-fixed paraffin embedded tissue, their relative performance on RNA
      obtained from other tissue types may vary, and needs future evaluation.

PMID- 21085669
TI  - Functional analysis of Ficolin-3 mediated complement activation.
AB  - The recognition molecules of the lectin complement pathway are mannose-binding
      lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to
      be associated with life threatening infections. Thus, we aimed to develop a
      functional method based on the ELISA platform for evaluating Ficolin-3 mediated
      complement activation that could be applicable for research and clinical use.
      Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase
      ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was
      evaluated, as was functional complement activation assessed by C4, C3 and
      terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a
      calcium dependent manner, while only minimal binding of Ficolin-2 and no binding
      of Ficolin-1 were observed. No binding to normal BSA was seen for any of the
      Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin
      3 in appropriate serum dilutions. Deposition of down stream complement components
      correlated highly significantly with the serum concentration of Ficolin-3 but not
      with Ficolin-2 in healthy donors. To make the assay robust for clinical use a
      chemical compound was applied to the samples that inhibited interference from the
      classical pathway due to the presence of anti-BSA antibodies in some sera. We
      describe a novel functional method for measuring complement activation mediated
      by Ficolin-3 in human serum up to the formation of TCC. The assay provides the
      possibility to diagnose functional and genetic defects of Ficolin-3 and down
      stream components in the lectin complement pathway.

PMID- 21085670
TI  - Functionalized positive nanoparticles reduce mucin swelling and dispersion.
AB  - Multi-functionalized nanoparticles (NPs) have been extensively investigated for
      their potential in household and commercial products, and biomedical
      applications. Previous reports have confirmed the cellular nanotoxicity and
      adverse inflammatory effects on pulmonary systems induced by NPs. However,
      possible health hazards resulting from mucus rheological disturbances induced by
      NPs are underexplored. Accumulation of viscous, poorly dispersed, and less
      transportable mucus leading to improper mucus rheology and dysfunctional
      mucociliary clearance are typically found to associate with many respiratory
      diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive
      Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its
      operational mechanisms have not been resolved. Herein, we report that positively
      charged functionalized NPs can hinder mucin gel hydration and effectively induce
      mucin aggregation. The positively charged NPs can significantly reduce the rate
      of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly
      increase the size of aggregated mucin by approximately 30 times within 24 hrs.
      EGTA chelation of indigenous mucin crosslinkers (Ca(2+) ions) was unable to
      effectively disperse NP-induced aggregated mucins. Our results have demonstrated
      that positively charged functionalized NPs can impede mucin gel swelling by
      crosslinking the matrix. This report also highlights the unexpected health risk
      of NP-induced change in mucus rheological properties resulting in possible
      mucociliary transport impairment on epithelial mucosa and related health
      problems. In addition, our data can serve as a prospective guideline for
      designing nanocarriers for airway drug delivery applications.

PMID- 21085671
TI  - Angiogenin levels and ANG genotypes: dysregulation in amyotrophic lateral
      sclerosis.
AB  - OBJECTIVE: To determine whether 5 single nucleotide polymorphisms (SNPs)
      associate with ALS in 3 different populations. We also assessed the contribution
      of genotype to angiogenin levels in plasma and CSF. METHODS: Allelic association
      statistics were calculated for polymorphisms in the ANG gene in 859 patients and
      1047 controls from Sweden, Ireland and Poland. Plasma, serum and CSF angiogenin
      levels were quantified and stratified according to genotypes across the ANG gene.
      The contribution of SNP genotypes to variance in circulating angiogenin levels
      was estimated in patients and controls. RESULTS: All SNPs showed association with
      ALS in the Irish group. The SNP rs17114699 replicated in the Swedish cohort. No
      SNP associated in the Polish cohort. Age- and sex-corrected circulating
      angiogenin levels were significantly lower in patients than in controls
      (p<0.001). An allele dose-dependent regulation of angiogenin levels was observed
      in controls. This regulation was attenuated in the ALS cohort. A significant
      positive correlation between CSF plasma angiogenin levels was present in controls
      and abolished in ALS. CONCLUSIONS: ANG variants associate with ALS in the Irish
      and Swedish populations, but not in the Polish. There is evidence of
      dysregulation of angiogenin expression in plasma and CSF in sporadic ALS.
      Angiogenin expression is likely to be important in the pathogenesis of ALS.

PMID- 21085672
TI  - Induction of glucose metabolism in stimulated T lymphocytes is regulated by
      mitogen-activated protein kinase signaling.
AB  - T lymphocytes play a critical role in cell-mediated immune responses. During
      activation, extracellular and intracellular signals alter T cell metabolism in
      order to meet the energetic and biosynthetic needs of a proliferating, active
      cell, but control of these phenomena is not well defined. Previous studies have
      demonstrated that signaling from the costimulatory receptor CD28 enhances glucose
      utilization via the phosphatidylinositol-3-kinase (PI3K) pathway. However, since
      CD28 ligation alone does not induce glucose metabolism in resting T cells,
      contributions from T cell receptor-initiated signaling pathways must also be
      important. We therefore investigated the role of mitogen-activated protein kinase
      (MAPK) signaling in the regulation of mouse T cell glucose metabolism. T cell
      stimulation strongly induces glucose uptake and glycolysis, both of which are
      severely impaired by inhibition of extracellular signal-regulated kinase (ERK),
      whereas p38 inhibition had a much smaller effect. Activation also induced
      hexokinase activity and expression in T cells, and both were similarly dependent
      on ERK signaling. Thus, the ERK signaling pathway cooperates with PI3K to induce
      glucose utilization in activated T cells, with hexokinase serving as a potential
      point for coordinated regulation.

PMID- 21085674
TI  - Pre-clinical drug prioritization via prognosis-guided genetic interaction
      networks.
AB  - The high rates of failure in oncology drug clinical trials highlight the problems
      of using pre-clinical data to predict the clinical effects of drugs. Patient
      population heterogeneity and unpredictable physiology complicate pre-clinical
      cancer modeling efforts. We hypothesize that gene networks associated with cancer
      outcome in heterogeneous patient populations could serve as a reference for
      identifying drug effects. Here we propose a novel in vivo genetic interaction
      which we call 'synergistic outcome determination' (SOD), a concept similar to
      'Synthetic Lethality'. SOD is defined as the synergy of a gene pair with respect
      to cancer patients' outcome, whose correlation with outcome is due to
      cooperative, rather than independent, contributions of genes. The method combines
      microarray gene expression data with cancer prognostic information to identify
      synergistic gene-gene interactions that are then used to construct interaction
      networks based on gene modules (a group of genes which share similar function).
      In this way, we identified a cluster of important epigenetically regulated gene
      modules. By projecting drug sensitivity-associated genes on to the cancer
      specific inter-module network, we defined a perturbation index for each drug
      based upon its characteristic perturbation pattern on the inter-module network.
      Finally, by calculating this index for compounds in the NCI Standard Agent
      Database, we significantly discriminated successful drugs from a broad set of
      test compounds, and further revealed the mechanisms of drug combinations. Thus,
      prognosis-guided synergistic gene-gene interaction networks could serve as an
      efficient in silico tool for pre-clinical drug prioritization and rational design
      of combinatorial therapies.

PMID- 21085673
TI  - The Arabidopsis ABA-activated kinase OST1 phosphorylates the bZIP transcription
      factor ABF3 and creates a 14-3-3 binding site involved in its turnover.
AB  - BACKGROUND: Genetic evidence in Arabidopsis thaliana indicates that members of
      the Snf1-Related Kinases 2 family (SnRK2) are essential in mediating various
      stress-adaptive responses. Recent reports have indeed shown that one particular
      member, Open Stomata (OST)1, whose kinase activity is stimulated by the stress
      hormone abscisic acid (ABA), is a direct target of negative regulation by the
      core ABA co-receptor complex composed of PYR/PYL/RCAR and clade A Protein
      Phosphatase 2C (PP2C) proteins. METHODOLOGY/PRINCIPAL FINDINGS: Here, the
      substrate preference of OST1 was interrogated at a genome-wide scale. We
      phosphorylated in vitro a bank of semi-degenerate peptides designed to assess the
      relative phosphorylation efficiency on a positionally fixed serine or threonine
      caused by systematic changes in the flanking amino acid sequence. Our results
      designate the ABA-responsive-element Binding Factor 3 (ABF3), which controls part
      of the ABA-regulated transcriptome, as a genuine OST1 substrate. Bimolecular
      Fluorescence Complementation experiments indicate that ABF3 interacts directly
      with OST1 in the nuclei of living plant cells. In vitro, OST1 phosphorylates ABF3
      on multiple LXRXXpS/T preferred motifs including T451 located in the midst of a
      conserved 14-3-3 binding site. Using an antibody sensitive to the phosphorylated
      state of the preferred motif, we further show that ABF3 is phosphorylated on at
      least one such motif in response to ABA in vivo and that phospho-T451 is
      important for stabilization of ABF3. CONCLUSIONS/SIGNIFICANCE: All together, our
      results suggest that OST1 phosphorylates ABF3 in vivo on T451 to create a 14-3-3
      binding motif. In a wider physiological context, we propose that the long term
      responses to ABA that require sustained gene expression is, in part, mediated by
      the stabilization of ABFs driven by ABA-activated SnRK2s.

PMID- 21085675
TI  - Regulation of the actin cytoskeleton by an interaction of IQGAP related protein
      GAPA with filamin and cortexillin I.
AB  - Filamin and Cortexillin are F-actin crosslinking proteins in Dictyostelium
      discoideum allowing actin filaments to form three-dimensional networks. GAPA, an
      IQGAP related protein, is required for cytokinesis and localizes to the cleavage
      furrow during cytokinesis. Here we describe a novel interaction with Filamin
      which is required for cytokinesis and regulation of the F-actin content. The
      interaction occurs through the actin binding domain of Filamin and the GRD domain
      of GAPA. A similar interaction takes place with Cortexillin I. We further report
      that Filamin associates with Rac1a implying that filamin might act as a scaffold
      for small GTPases. Filamin and activated Rac associate with GAPA to regulate
      actin remodelling. Overexpression of filamin and GAPA in the various strains
      suggests that GAPA regulates the actin cytoskeleton through interaction with
      Filamin and that it controls cytokinesis through association with Filamin and
      Cortexillin.

PMID- 21085676
TI  - Expansion and characterization of human melanoma tumor-infiltrating lymphocytes
      (TILs).
AB  - BACKGROUND: Various immunotherapeutic strategies for cancer are aimed at
      augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT),
      where T cells are manipulated ex vivo and subsequently re-infused in an
      autologous manner, has been performed using T cells from various sources. Some of
      the highest clinical response rates for metastatic melanoma have been reported in
      trials using tumor-infiltrating lymphocytes (TILs). These protocols still have
      room for improvement and furthermore are currently only performed at a limited
      number of institutions. The goal of this work was to develop TILs as a
      therapeutic product at our institution. PRINCIPAL FINDINGS: TILs from 40 melanoma
      tissue specimens were expanded and characterized. Under optimized culture
      conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at
      least one culture reaching >=3*10(7) TILs within 4 weeks. Flow cytometric
      analyses showed that cultures were predominantly CD3+ T cells, with highly
      variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures
      were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor
      reactivity based on IFN-gamma production and/or cytotoxic activity. Thirteen
      percent (19/148) showed specific cytotoxic activity but not IFN-gamma production
      and only 1% (2/148) showed specific IFN-gamma production but not cytotoxic
      activity. Further expansion of TILs using a 14-day "rapid expansion protocol"
      (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to
      generate sufficient numbers of cells for current ACT protocols. Thirty-eight
      consecutive test REPs were performed with an average 1865-fold expansion (+/-
      1034-fold) after 14 days. CONCLUSIONS: TILs generally expanded efficiently and
      tumor reactivity could be detected in vitro. These preclinical data from melanoma
      TILs lay the groundwork for clinical trials of ACT.

PMID- 21085677
TI  - EBP1 is a novel E2F target gene regulated by transforming growth factor-beta.
AB  - Regulation of gene expression requires transcription factor binding to specific
      DNA elements, and a large body of work has focused on the identification of such
      sequences. However, it is becoming increasingly clear that eukaryotic
      transcription factors can exhibit widespread, nonfunctional binding to genomic
      DNA sites. Conversely, some of these proteins, such as E2F, can also modulate
      gene expression by binding to non-consensus elements. E2F comprises a family of
      transcription factors that play key roles in a wide variety of cellular
      functions, including survival, differentiation, activation during tissue
      regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding
      protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1
      promoter occurs through two tandem DNA elements that do not conform to typical
      consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking
      one, but not both sites, suggesting a degree of redundancy under certain
      conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma
      and other transformed cell lines. In contrast, in non-transformed primary
      epidermal keratinocytes, E2F, together with the retinoblastoma family of
      proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to
      growth inhibition by transforming growth factor-beta1. Thus, E2F is likely a
      central coordinator of multiple responses that culminate in regulation of EBP1
      gene expression, and which may vary depending on cell type and context.

PMID- 21085678
TI  - Finding the way with a noisy brain.
AB  - Successful navigation is fundamental to the survival of nearly every animal on
      earth, and achieved by nervous systems of vastly different sizes and
      characteristics. Yet surprisingly little is known of the detailed neural
      circuitry from any species which can accurately represent space for navigation.
      Path integration is one of the oldest and most ubiquitous navigation strategies
      in the animal kingdom. Despite a plethora of computational models, from
      equational to neural network form, there is currently no consensus, even in
      principle, of how this important phenomenon occurs neurally. Recently, all path
      integration models were examined according to a novel, unifying classification
      system. Here we combine this theoretical framework with recent insights from
      directed walk theory, and develop an intuitive yet mathematically rigorous proof
      that only one class of neural representation of space can tolerate noise during
      path integration. This result suggests many existing models of path integration
      are not biologically plausible due to their intolerance to noise. This surprising
      result imposes significant computational limitations on the neurobiological
      spatial representation of all successfully navigating animals, irrespective of
      species. Indeed, noise-tolerance may be an important functional constraint on the
      evolution of neuroarchitectural plans in the animal kingdom.

PMID- 21085679
TI  - Analysis of stochastic strategies in bacterial competence: a master equation
      approach.
AB  - Competence is a transiently differentiated state that certain bacterial cells
      reach when faced with a stressful environment. Entrance into competence can be
      attributed to the excitability of the dynamics governing the genetic circuit that
      regulates this cellular behavior. Like many biological behaviors, entrance into
      competence is a stochastic event. In this case cellular noise is responsible for
      driving the cell from a vegetative state into competence and back. In this work
      we present a novel numerical method for the analysis of stochastic biochemical
      events and use it to study the excitable dynamics responsible for competence in
      Bacillus subtilis. Starting with a Finite State Projection (FSP) solution of the
      chemical master equation (CME), we develop efficient numerical tools for
      accurately computing competence probability. Additionally, we propose a new
      approach for the sensitivity analysis of stochastic events and utilize it to
      elucidate the robustness properties of the competence regulatory genetic circuit.
      We also propose and implement a numerical method to calculate the expected time
      it takes a cell to return from competence. Although this study is focused on an
      example of cell-differentiation in Bacillus subtilis, our approach can be applied
      to a wide range of stochastic phenomena in biological systems.

PMID- 21085680
TI  - Chromosome driven spatial patterning of proteins in bacteria.
AB  - The spatial patterning of proteins in bacteria plays an important role in many
      processes, from cell division to chemotaxis. In the asymmetrically dividing
      bacteria Caulobacter crescentus, a scaffolding protein, PopZ, localizes to both
      poles and aids the differential patterning of proteins between mother and
      daughter cells during division. Polar patterning of misfolded proteins in
      Escherichia coli has also been shown, and likely plays an important role in
      cellular ageing. Recent experiments on both of the above systems suggest that the
      presence of chromosome free regions along with protein multimerization may be a
      mechanism for driving the polar localization of proteins. We have developed a
      simple physical model for protein localization using only these two driving
      mechanisms. Our model reproduces all the observed patterns of PopZ and misfolded
      protein localization--from diffuse, unipolar, and bipolar patterns and can also
      account for the observed patterns in a variety of mutants. The model also
      suggests new experiments to further test the role of the chromosome in driving
      protein patterning, and whether such a mechanism is responsible for helping to
      drive the differentiation of the cell poles.

PMID- 21085681
TI  - Spike-timing-based computation in sound localization.
AB  - Spike timing is precise in the auditory system and it has been argued that it
      conveys information about auditory stimuli, in particular about the location of a
      sound source. However, beyond simple time differences, the way in which neurons
      might extract this information is unclear and the potential computational
      advantages are unknown. The computational difficulty of this task for an animal
      is to locate the source of an unexpected sound from two monaural signals that are
      highly dependent on the unknown source signal. In neuron models consisting of
      spectro-temporal filtering and spiking nonlinearity, we found that the binaural
      structure induced by spatialized sounds is mapped to synchrony patterns that
      depend on source location rather than on source signal. Location-specific
      synchrony patterns would then result in the activation of location-specific
      assemblies of postsynaptic neurons. We designed a spiking neuron model which
      exploited this principle to locate a variety of sound sources in a virtual
      acoustic environment using measured human head-related transfer functions. The
      model was able to accurately estimate the location of previously unknown sounds
      in both azimuth and elevation (including front/back discrimination) in a known
      acoustic environment. We found that multiple representations of different
      acoustic environments could coexist as sets of overlapping neural assemblies
      which could be associated with spatial locations by Hebbian learning. The model
      demonstrates the computational relevance of relative spike timing to extract
      spatial information about sources independently of the source signal.

PMID- 21085682
TI  - Modelling vesicular release at hippocampal synapses.
AB  - We study local calcium dynamics leading to a vesicle fusion in a stochastic, and
      spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The
      kinetic model for vesicle release has two calcium sensors, a sensor for fast
      synchronous release that lasts a few tens of milliseconds and a separate sensor
      for slow asynchronous release that lasts a few hundred milliseconds. A wide range
      of data can be accounted for consistently only when a refractory period lasting a
      few milliseconds between releases is included. The inclusion of a second sensor
      for asynchronous release with a slow unbinding site, and thereby a long memory,
      affects short-term plasticity by facilitating release. Our simulations also
      reveal a third time scale of vesicle release that is correlated with the stimulus
      and is distinct from the fast and the slow releases. In these detailed Monte
      Carlo simulations all three time scales of vesicle release are insensitive to the
      spatial details of the synaptic ultrastructure. Furthermore, our simulations
      allow us to identify features of synaptic transmission that are universal and
      those that are modulated by structure.

PMID- 21085684
TI  - Phospholipase D family member 4, a transmembrane glycoprotein with no
      phospholipase D activity, expression in spleen and early postnatal microglia.
AB  - BACKGROUND: Phospholipase D (PLD) catalyzes conversion of phosphatidylcholine
      into choline and phosphatidic acid, leading to a variety of intracellular signal
      transduction events. Two classical PLDs, PLD1 and PLD2, contain
      phosphatidylinositide-binding PX and PH domains and two conserved His-x-Lys
      (x)(4)-Asp (HKD) motifs, which are critical for PLD activity. PLD4 officially
      belongs to the PLD family, because it possesses two HKD motifs. However, it lacks
      PX and PH domains and has a putative transmembrane domain instead. Nevertheless,
      little is known regarding expression, structure, and function of PLD4.
      METHODOLOGY/PRINCIPAL FINDINGS: PLD4 was analyzed in terms of expression,
      structure, and function. Expression was analyzed in developing mouse brains and
      non-neuronal tissues using microarray, in situ hybridization,
      immunohistochemistry, and immunocytochemistry. Structure was evaluated using
      bioinformatics analysis of protein domains, biochemical analyses of transmembrane
      property, and enzymatic deglycosylation. PLD activity was examined by choline
      release and transphosphatidylation assays. Results demonstrated low to modest,
      but characteristic, PLD4 mRNA expression in a subset of cells preferentially
      localized around white matter regions, including the corpus callosum and
      cerebellar white matter, during the first postnatal week. These PLD4 mRNA
      expressing cells were identified as Iba1-positive microglia. In non-neuronal
      tissues, PLD4 mRNA expression was widespread, but predominantly distributed in
      the spleen. Intense PLD4 expression was detected around the marginal zone of the
      splenic red pulp, and splenic PLD4 protein recovered from subcellular membrane
      fractions was highly N-glycosylated. PLD4 was heterologously expressed in cell
      lines and localized in the endoplasmic reticulum and Golgi apparatus. Moreover,
      heterologously expressed PLD4 proteins did not exhibit PLD enzymatic activity.
      CONCLUSIONS/SIGNIFICANCE: Results showed that PLD4 is a non-PLD, HKD motif
      carrying, transmembrane glycoprotein localized in the endoplasmic reticulum and
      Golgi apparatus. The spatiotemporally restricted expression patterns suggested
      that PLD4 might play a role in common function(s) among microglia during early
      postnatal brain development and splenic marginal zone cells.

PMID- 21085683
TI  - High ALDH activity identifies chemotherapy-resistant Ewing's sarcoma stem cells
      that retain sensitivity to EWS-FLI1 inhibition.
AB  - BACKGROUND: Cancer stem cells are a chemotherapy-resistant population capable of
      self-renewal and of regenerating the bulk tumor, thereby causing relapse and
      patient death. Ewing's sarcoma, the second most common form of bone tumor in
      adolescents and young adults, follows a clinical pattern consistent with the
      Cancer Stem Cell model - remission is easily achieved, even for patients with
      metastatic disease, but relapse remains frequent and is usually fatal.
      METHODOLOGY/PRINCIPAL FINDINGS: We have isolated a subpopulation of Ewing's
      sarcoma cells, from both human cell lines and human xenografts grown in immune
      deficient mice, which express high aldehyde dehydrogenase (ALDH(high)) activity
      and are enriched for clonogenicity, sphere-formation, and tumor initiation. The
      ALDH(high) cells are resistant to chemotherapy in vitro, but this can be overcome
      by the ATP binding cassette transport protein inhibitor, verapamil. Importantly,
      these cells are not resistant to YK-4-279, a small molecule inhibitor of EWS-FLI1
      that is selectively toxic to Ewing's sarcoma cells both in vitro and in vivo.
      CONCLUSIONS/SIGNIFICANCE: Ewing's sarcoma contains an ALDH(high) stem-like
      population of chemotherapy-resistant cells that retain sensitivity to EWS-FLI1
      inhibition. Inhibiting the EWS-FLI1 oncoprotein may prove to be an effective
      means of improving patient outcomes by targeting Ewing's sarcoma stem cells that
      survive standard chemotherapy.

PMID- 21085685
TI  - alpha-actinin-4 is essential for maintaining the spreading, motility and
      contractility of fibroblasts.
AB  - BACKGROUND: alpha-Actinins cross-link actin filaments, with this cross-linking
      activity regulating the formation of focal adhesions, intracellular tension, and
      cell migration. Most non-muscle cells such as fibroblasts express two isoforms,
      alpha-actinin-1 (ACTN1) and alpha-actinin-4 (ACTN4). The high homology between
      these two isoforms would suggest redundancy of their function, but recent studies
      have suggested different regulatory roles. Interestingly, ACTN4 is phosphorylated
      upon growth factor stimulation, and this loosens its interaction with actin.
      METHODOLOGY/PRINCIPAL FINDINGS: Using molecular, biochemical and cellular
      techniques, we probed the cellular functions of ACTN4 in fibroblasts. Knockdown
      of ACTN4 expression in murine lung fibroblasts significantly impaired cell
      migration, spreading, adhesion, and proliferation. Surprisingly, knockdown of
      ACTN4 enhanced cellular compaction and contraction force, and increased cellular
      and nuclear cross-sectional area. These results, except the increased
      contractility, are consistent with a putative role of ACTN4 in cytokinesis. For
      the transcellular tension, knockdown of ACTN4 significantly increased the
      expression of myosin light chain 2, a element of the contractility machinery. Re
      expression of wild type human ACTN4 in ACTN4 knockdown murine lung fibroblasts
      reverted cell spreading, cellular and nuclear cross-sectional area, and
      contractility back towards baseline, demonstrating that the defect was due to
      absence of ACTN4. SIGNIFICANCE: These results suggest that ACTN4 is essential for
      maintaining normal spreading, motility, cellular and nuclear cross-sectional
      area, and contractility of murine lung fibroblasts by maintaining the balance
      between transcellular contractility and cell-substratum adhesion.

PMID- 21085686
TI  - Optimizing vaccine allocation at different points in time during an epidemic.
AB  - BACKGROUND: Pandemic influenza A(H1N1) 2009 began spreading around the globe in
      April of 2009 and vaccination started in October of 2009. In most countries, by
      the time vaccination started, the second wave of pandemic H1N1 2009 was already
      under way. With limited supplies of vaccine, we are left to question whether it
      may be a good strategy to vaccinate the high-transmission groups earlier in the
      epidemic, but it might be a better use of resources to protect instead the high
      risk groups later in the epidemic. To answer this question, we develop a
      deterministic epidemic model with two age-groups (children and adults) and
      further subdivide each age group in low and high risk. METHODS AND FINDINGS: We
      COMPARE optimal vaccination strategies started at various points in time in two
      different. SETTINGS: a population in a developed country where children account
      for 24% of the population, and a population in a less developed country where
      children make up the majority of the population, 55%. For each of these
      populations, we minimize mortality or hospitalizations and we find an optimal
      vaccination strategy that gives the best vaccine allocation given a starting
      vaccination time and vaccine coverage level. We find that population structure is
      an important factor in determining the optimal vaccine distribution. Moreover,
      the optimal policy is dynamic as there is a switch in the optimal vaccination
      strategy at some time point just before the peak of the epidemic. For instance,
      with 25% vaccine coverage, it is better to protect the high-transmission groups
      before this point, but it is optimal to protect the most vulnerable groups
      afterward. CONCLUSIONS: Choosing the optimal strategy before or early in the
      epidemic makes an important difference in minimizing the number of influenza
      infections, and consequently the number of influenza deaths or hospitalizations,
      but the optimal strategy makes little difference after the peak.

PMID- 21085688
TI  - Ancient DNA indicates farmers, not just farming, spread West.

PMID- 21085687
TI  - Epigenetic silencing of spermatocyte-specific and neuronal genes by SUMO
      modification of the transcription factor Sp3.
AB  - SUMO modification of transcription factors is linked to repression of
      transcription. The physiological significance of SUMO attachment to a particular
      transcriptional regulator, however, is largely unknown. We have employed the
      ubiquitously expressed murine transcription factor Sp3 to analyze the role of
      SUMOylation in vivo. We generated mice and mouse embryonic fibroblasts (MEFs)
      carrying a subtle point mutation in the SUMO attachment sequence of Sp3
      (IKEE(553)D mutation). The E(553)D mutation impedes SUMOylation of Sp3 at
      K(551)in vivo, without affecting Sp3 protein levels. Expression profiling
      revealed that spermatocyte-specific genes, such as Dmc1 and Dnahc8, and neuronal
      genes, including Paqr6, Rims3, and Robo3, are de-repressed in non-testicular and
      extra-neuronal mouse tissues and in mouse embryonic fibroblasts expressing the
      SUMOylation-deficient Sp3E(553)D mutant protein. Chromatin immunoprecipitation
      experiments show that transcriptional de-repression of these genes is accompanied
      by the loss of repressive heterochromatic marks such as H3K9 and H4K20 tri
      methylation and impaired recruitment of repressive chromatin-modifying enzymes.
      Finally, analysis of the DNA methylation state of the Dmc1, Paqr6, and Rims3
      promoters by bisulfite sequencing revealed that these genes are highly methylated
      in Sp3wt MEFs but are unmethylated in Sp3E(553)D MEFs linking SUMOylation of Sp3
      to tissue-specific CpG methylation. Our results establish SUMO conjugation to Sp3
      as a molecular beacon for the assembly of repression machineries to maintain
      tissue-specific transcriptional gene silencing.

PMID- 21085690
TI  - Genetic control of organ shape and tissue polarity.
AB  - The mechanisms by which genes control organ shape are poorly understood. In
      principle, genes may control shape by modifying local rates and/or orientations
      of deformation. Distinguishing between these possibilities has been difficult
      because of interactions between patterns, orientations, and mechanical
      constraints during growth. Here we show how a combination of growth analysis,
      molecular genetics, and modelling can be used to dissect the factors contributing
      to shape. Using the Snapdragon (Antirrhinum) flower as an example, we show how
      shape development reflects local rates and orientations of tissue growth that
      vary spatially and temporally to form a dynamic growth field. This growth field
      is under the control of several dorsoventral genes that influence flower shape.
      The action of these genes can be modelled by assuming they modulate specified
      growth rates parallel or perpendicular to local orientations, established by a
      few key organisers of tissue polarity. Models in which dorsoventral genes only
      influence specified growth rates do not fully account for the observed growth
      fields and shapes. However, the data can be readily explained by a model in which
      dorsoventral genes also modify organisers of tissue polarity. In particular,
      genetic control of tissue polarity organisers at ventral petal junctions and
      distal boundaries allows both the shape and growth field of the flower to be
      accounted for in wild type and mutants. The results suggest that genetic control
      of tissue polarity organisers has played a key role in the development and
      evolution of shape.

PMID- 21085689
TI  - Ancient DNA from European early neolithic farmers reveals their near eastern
      affinities.
AB  - In Europe, the Neolithic transition (8,000-4,000 B.C.) from hunting and gathering
      to agricultural communities was one of the most important demographic events
      since the initial peopling of Europe by anatomically modern humans in the Upper
      Paleolithic (40,000 B.C.). However, the nature and speed of this transition is a
      matter of continuing scientific debate in archaeology, anthropology, and human
      population genetics. To date, inferences about the genetic make up of past
      populations have mostly been drawn from studies of modern-day Eurasian
      populations, but increasingly ancient DNA studies offer a direct view of the
      genetic past. We genetically characterized a population of the earliest farming
      culture in Central Europe, the Linear Pottery Culture (LBK; 5,500-4,900
      calibrated B.C.) and used comprehensive phylogeographic and population genetic
      analyses to locate its origins within the broader Eurasian region, and to trace
      potential dispersal routes into Europe. We cloned and sequenced the mitochondrial
      hypervariable segment I and designed two powerful SNP multiplex PCR systems to
      generate new mitochondrial and Y-chromosomal data from 21 individuals from a
      complete LBK graveyard at Derenburg Meerenstieg II in Germany. These results
      considerably extend the available genetic dataset for the LBK (n = 42) and permit
      the first detailed genetic analysis of the earliest Neolithic culture in Central
      Europe (5,500-4,900 calibrated B.C.). We characterized the Neolithic
      mitochondrial DNA sequence diversity and geographical affinities of the early
      farmers using a large database of extant Western Eurasian populations (n =
      23,394) and a wide range of population genetic analyses including shared
      haplotype analyses, principal component analyses, multidimensional scaling,
      geographic mapping of genetic distances, and Bayesian Serial Simcoal analyses.
      The results reveal that the LBK population shared an affinity with the modern-day
      Near East and Anatolia, supporting a major genetic input from this area during
      the advent of farming in Europe. However, the LBK population also showed unique
      genetic features including a clearly distinct distribution of mitochondrial
      haplogroup frequencies, confirming that major demographic events continued to
      take place in Europe after the early Neolithic.

PMID- 21085691
TI  - First-borns carry a higher metabolic risk in early adulthood: evidence from a
      prospective cohort study.
AB  - BACKGROUND: Birth order has been associated with early growth variability and
      subsequent increased adiposity, but the consequent effects of increased fat mass
      on metabolic risk during adulthood have not been assessed. We aimed to quantify
      the metabolic risk in young adulthood of being first-born relative to those born
      second or subsequently. METHODOLOGY AND PRINCIPAL FINDINGS: Body composition and
      metabolic risk were assessed in 2,249 men, aged 17-19 years, from a birth cohort
      in southern Brazil. Metabolic risk was assessed using a composite z-score
      integrating standardized measurements of blood pressure, total cholesterol, high
      density lipoprotein, triglycerides and fat mass. First-borns had lower birth
      weight z-score (Delta = -0.25, 95%CI -0.35, -0.15,p<0.001) but showed greater
      weight gain during infancy (change in weight z-score from birth to 20 months:
      Delta = 0.39, 95%CI 0.28-0.50, p<0.0001) and had greater mean height (Delta = 1.2
      cm, 95%CI: 0.7-1.6, p<0.0001) and weight (Delta = 0.34 kg, 95%CI: 0.13-0.55,
      p<0.002) at 43 months. This greater weight and height tracked into early
      adulthood, with first-borns being significantly taller, heavier and with
      significantly higher fat mass than later-borns. The metabolic risk z-score was
      significantly higher in first-borns. CONCLUSIONS/SIGNIFICANCE: First-born status
      is associated with significantly elevated adiposity and metabolic risk in young
      adult men in Brazil. Our results, linking cardiovascular risk with life history
      variables, suggest that metabolic risk may be associated with the worldwide trend
      to smaller family size and it may interact with changes in behavioural or
      environmental risk factors.

PMID- 21085692
TI  - Water supply and health.

PMID- 21085693
TI  - The DNA methylome of human peripheral blood mononuclear cells.
AB  - DNA methylation plays an important role in biological processes in human health
      and disease. Recent technological advances allow unbiased whole-genome DNA
      methylation (methylome) analysis to be carried out on human cells. Using whole
      genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we
      report a comprehensive (92.62%) methylome and analysis of the unique sequences in
      human peripheral blood mononuclear cells (PBMC) from the same Asian individual
      whose genome was deciphered in the YH project. PBMC constitute an important
      source for clinical blood tests world-wide. We found that 68.4% of CpG sites and
      <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine
      methylation is minor in human PBMC. Analysis of the PBMC methylome revealed a
      rich epigenomic landscape for 20 distinct genomic features, including regulatory,
      protein-coding, non-coding, RNA-coding, and repeat sequences. Integration of our
      methylome data with the YH genome sequence enabled a first comprehensive
      assessment of allele-specific methylation (ASM) between the two haploid
      methylomes of any individual and allowed the identification of 599 haploid
      differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes
      had hDMRs within 2 kb of their transcriptional start sites of which >80%
      displayed allele-specific expression (ASE). These data demonstrate that ASM is a
      recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together
      with recently reported similar studies, our study provides a comprehensive
      resource for future epigenomic research and confirms new sequencing technology as
      a paradigm for large-scale epigenomics studies.

PMID- 21085694
TI  - Hygiene, sanitation, and water: forgotten foundations of health.

PMID- 21085695
TI  - Quantitative control of organ shape by combinatorial gene activity.
AB  - The development of organs with particular shapes, like wings or flowers, depends
      on regional activity of transcription factors and signalling molecules. However,
      the mechanisms that link these molecular activities to the morphogenetic events
      underlying shape are poorly understood. Here we describe a combination of
      experimental and computational approaches that address this problem, applying
      them to a group of genes controlling flower shape in the Snapdragon
      (Antirrhinum). Four transcription factors are known to play a key role in the
      control of floral shape and asymmetry in Snapdragon. We use quantitative shape
      analysis of mutants for these factors to define principal components underlying
      flower shape variation. We show that each transcription factor has a specific
      effect on the shape and size of regions within the flower, shifting the position
      of the flower in shape space. These shifts are further analysed by generating
      double mutants and lines that express some of the genes ectopically. By
      integrating these observations with known gene expression patterns and
      interactions, we arrive at a combinatorial scheme for how regional effects on
      shape are genetically controlled. We evaluate our scheme by incorporating the
      proposed interactions into a generative model, where the developing flower is
      treated as a material sheet that grows according to how genes modify local
      polarities and growth rates. The petal shapes generated by the model show a good
      quantitative match with those observed experimentally for each petal in numerous
      genotypes, thus validating the hypothesised scheme. This article therefore shows
      how complex shapes can be accounted for by combinatorial effects of transcription
      factors on regional growth properties. This finding has implications not only for
      how shapes develop but also for how they may have evolved through tinkering with
      transcription factors and their targets.

PMID- 21085696
TI  - Strategies for increasing recruitment to randomised controlled trials: systematic
      review.
AB  - BACKGROUND: Recruitment of participants into randomised controlled trials (RCTs)
      is critical for successful trial conduct. Although there have been two previous
      systematic reviews on related topics, the results (which identified specific
      interventions) were inconclusive and not generalizable. The aim of our study was
      to evaluate the relative effectiveness of recruitment strategies for
      participation in RCTs. METHODS AND FINDINGS: A systematic review, using the
      PRISMA guideline for reporting of systematic reviews, that compared methods of
      recruiting individual study participants into an actual or mock RCT were
      included. We searched MEDLINE, Embase, The Cochrane Library, and reference lists
      of relevant studies. From over 16,000 titles or abstracts reviewed, 396 papers
      were retrieved and 37 studies were included, in which 18,812 of at least 59,354
      people approached agreed to participate in a clinical RCT. Recruitment strategies
      were broadly divided into four groups: novel trial designs (eight studies),
      recruiter differences (eight studies), incentives (two studies), and provision of
      trial information (19 studies). Strategies that increased people's awareness of
      the health problem being studied (e.g., an interactive computer program [relative
      risk (RR) 1.48, 95% confidence interval (CI) 1.00-2.18], attendance at an
      education session [RR 1.14, 95% CI 1.01-1.28], addition of a health questionnaire
      [RR 1.37, 95% CI 1.14-1.66]), or a video about the health condition (RR 1.75, 95%
      CI 1.11-2.74), and also monetary incentives (RR1.39, 95% CI 1.13-1.64 to RR 1.53,
      95% CI 1.28-1.84) improved recruitment. Increasing patients' understanding of the
      trial process, recruiter differences, and various methods of randomisation and
      consent design did not show a difference in recruitment. Consent rates were also
      higher for nonblinded trial design, but differential loss to follow up between
      groups may jeopardise the study findings. The study's main limitation was the
      necessity of modifying the search strategy with subsequent search updates because
      of changes in MEDLINE definitions. The abstracts of previous versions of this
      systematic review were published in 2002 and 2007. CONCLUSION: Recruitment
      strategies that focus on increasing potential participants' awareness of the
      health problem being studied, its potential impact on their health, and their
      engagement in the learning process appeared to increase recruitment to clinical
      studies. Further trials of recruitment strategies that target engaging
      participants to increase their awareness of the health problems being studied and
      the potential impact on their health may confirm this hypothesis. Please see
      later in the article for the Editors' Summary.

PMID- 21085697
TI  - Does cataract surgery alleviate poverty? Evidence from a multi-centre
      intervention study conducted in Kenya, the Philippines and Bangladesh.
AB  - BACKGROUND: Poverty and blindness are believed to be intimately linked, but
      empirical data supporting this purported relationship are sparse. The objective
      of this study is to assess whether there is a reduction in poverty after cataract
      surgery among visually impaired cases. METHODOLOGY/PRINCIPAL FINDINGS: A multi
      centre intervention study was conducted in three countries (Kenya, Philippines,
      Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership
      and self-rated wealth) were collected from cases aged >=50 years who were
      visually impaired due to cataract (visual acuity<6/24 in the better eye) and age
      sex matched controls with normal vision. Cases were offered free/subsidised
      cataract surgery. Approximately one year later participants were re-interviewed
      about poverty. 466 cases and 436 controls were examined at both baseline and
      follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases
      had undergone cataract surgery ("operated cases"). At baseline, operated cases
      were poorer compared to controls in terms of PCE (Kenya: $22 versus L35 p = 0.02,
      Bangladesh: $16 vs $24 p = 0.004, Philippines: $24 vs 32 p = 0.0007), assets and
      self-rated wealth. By follow-up PCE had increased significantly among operated
      cases in each of the three settings to the level of controls (Kenya: $30 versus
      L36 p = 0.49, Bangladesh: $23 vs $23 p = 0.20, Philippines: $45 vs $36 p = 0.68).
      There were smaller increases in self-rated wealth and no changes in assets.
      Changes in PCE were apparent in different socio-demographic and ocular groups.
      The largest PCE increases were apparent among the cases that were poorest at
      baseline. CONCLUSIONS/SIGNIFICANCE: This study showed that cataract surgery can
      contribute to poverty alleviation, particularly among the most vulnerable members
      of society. This study highlights the need for increased provision of cataract
      surgery to poor people and shows that a focus on blindness may help to alleviate
      poverty and achieve the Millennium Development Goals.

PMID- 21085699
TI  - Heat resistance mediated by a new plasmid encoded Clp ATPase, ClpK, as a possible
      novel mechanism for nosocomial persistence of Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae is an important opportunistic pathogen and a frequent cause
      of nosocomial infections. We have characterized a K. pneumoniae strain
      responsible for a series of critical infections in an intensive care unit over a
      two-year period. The strain was found to be remarkably thermotolerant providing a
      conceivable explanation of its persistence in the hospital environment. This
      marked phenotype is mediated by a novel type of Clp ATPase, designated ClpK. The
      clpK gene is encoded by a conjugative plasmid and we find that the clpK gene
      alone renders an otherwise sensitive E. coli strain resistant to lethal heat
      shock. Furthermore, one third of a collection of nosocomial K. pneumoniae
      isolates carry clpK and exhibit a heat resistant phenotype. The discovery of ClpK
      as a plasmid encoded factor and its profound impact on thermal stress survival
      sheds new light on the biological relevance of Clp ATPases in acquired
      environmental fitness and highlights the challenges of mobile genetic elements in
      fighting nosocomial infections.

PMID- 21085698
TI  - Delineation of the innate and adaptive T-cell immune outcome in the human host in
      response to Campylobacter jejuni infection.
AB  - BACKGROUND: Campylobacter jejuni is the most prevalent cause of bacterial
      gastroenteritis worldwide. Despite the significant health burden this infection
      presents, molecular understanding of C. jejuni-mediated disease pathogenesis
      remains poorly defined. Here, we report the characterisation of the early, innate
      immune response to C. jejuni using an ex-vivo human gut model of infection.
      Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated
      immunity was also sought. METHODOLOGY: Healthy, control paediatric terminal ileum
      or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial
      colonisation was followed by confocal microscopy and mucosal innate immune
      responses measured by ELISA. Marked induction of IFNgamma with modest increase in
      IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1beta and IL-6
      were indicative of a cytokine milieu that may modulate subsequent T-cell mediated
      immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was
      followed by analyses of T cell immune responses utilising flow cytometry and
      ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells
      and corresponding cytokines was observed. The ability of IFNgamma, IL-22 and IL
      17 cytokines to exert host defence via modulation of C. jejuni adhesion and
      invasion to intestinal epithelia was measured by standard gentamicin protection
      assay. CONCLUSIONS: Both innate and adaptive T cell-immunity to C. jejuni
      infection led to the release of IFNgamma, IL-22 and IL-17A; suggesting a critical
      role for this cytokine triad in establishing host anti-microbial immunity during
      the acute and effectors phase of infection. In addition, to their known anti
      microbial functions; IL-17A and IL-17F reduced the number of intracellular C.
      jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family
      members may contribute to protective immunity against C. jejuni.

PMID- 21085700
TI  - Advances in the use of DNA barcodes to build a community phylogeny for tropical
      trees in a Puerto Rican forest dynamics plot.
AB  - BACKGROUND: Species number, functional traits, and phylogenetic history all
      contribute to characterizing the biological diversity in plant communities. The
      phylogenetic component of diversity has been particularly difficult to quantify
      in species-rich tropical tree assemblages. The compilation of previously
      published (and often incomplete) data on evolutionary relationships of species
      into a composite phylogeny of the taxa in a forest, through such programs as
      Phylomatic, has proven useful in building community phylogenies although often of
      limited resolution. Recently, DNA barcodes have been used to construct a robust
      community phylogeny for nearly 300 tree species in a forest dynamics plot in
      Panama using a supermatrix method. In that study sequence data from three barcode
      loci were used to generate a well-resolved species-level phylogeny.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we expand upon this earlier investigation
      and present results on the use of a phylogenetic constraint tree to generate a
      community phylogeny for a diverse, tropical forest dynamics plot in Puerto Rico.
      This enhanced method of phylogenetic reconstruction insures the congruence of the
      barcode phylogeny with broadly accepted hypotheses on the phylogeny of flowering
      plants (i.e., APG III) regardless of the number and taxonomic breadth of the taxa
      sampled. We also compare maximum parsimony versus maximum likelihood estimates of
      community phylogenetic relationships as well as evaluate the effectiveness of one
      versus two- versus three-gene barcodes in resolving community evolutionary
      history. CONCLUSIONS/SIGNIFICANCE: As first demonstrated in the Panamanian forest
      dynamics plot, the results for the Puerto Rican plot illustrate that highly
      resolved phylogenies derived from DNA barcode sequence data combined with a
      constraint tree based on APG III are particularly useful in comparative analysis
      of phylogenetic diversity and will enhance research on the interface between
      community ecology and evolution.

PMID- 21085701
TI  - DNA copy number changes in human malignant fibrous histiocytomas by array
      comparative genomic hybridisation.
AB  - BACKGROUND: Malignant fibrous histiocytomas (MFHs), or undifferentiated
      pleomorphic sarcomas, are in general high-grade tumours with extensive
      chromosomal aberrations. In order to identify recurrent chromosomal regions of
      gain and loss, as well as novel gene targets of potential importance for MFH
      development and/or progression, we have analysed DNA copy number changes in 33
      MFHs using microarray-based comparative genomic hybridisation (array CGH).
      PRINCIPAL FINDINGS: In general, the tumours showed numerous gains and losses of
      large chromosomal regions. The most frequent minimal recurrent regions of gain
      were 1p33-p32.3, 1p31.3-p31.2 and 1p21.3 (all gained in 58% of the samples), as
      well as 1q21.2-q21.3 and 20q13.2 (both 55%). The most frequent minimal recurrent
      regions of loss were 10q25.3-q26.11, 13q13.3-q14.2 and 13q14.3-q21.1 (all lost in
      64% of the samples), as well as 2q36.3-q37.2 (61%), 1q41 (55%) and 16q12.1-q12.2
      (52%). Statistical analyses revealed that gain of 1p33-p32.3 and 1p21.3 was
      significantly associated with better patient survival (P = 0.021 and 0.046,
      respectively). Comparison with similar array CGH data from 44 leiomyosarcomas
      identified seven chromosomal regions; 1p36.32-p35.2, 1p21.3-p21.1, 1q32.1-q42.13,
      2q14.1-q22.2, 4q33-q34.3, 6p25.1-p21.32 and 7p22.3-p13, which were significantly
      different in copy number between the MFHs and leiomyosarcomas. CONCLUSIONS: A
      number of recurrent regions of gain and loss have been identified, some of which
      were associated with better patient survival. Several specific chromosomal
      regions with significant differences in copy number between MFHs and
      leiomyosarcomas were identified, and these aberrations may be used as additional
      tools for the differential diagnosis of MFHs and leiomyosarcomas.

PMID- 21085702
TI  - Structural relationships in the lysozyme superfamily: significant evidence for
      glycoside hydrolase signature motifs.
AB  - BACKGROUND: Chitin is a polysaccharide that forms the hard, outer shell of
      arthropods and the cell walls of fungi and some algae. Peptidoglycan is a polymer
      of sugars and amino acids constituting the cell walls of most bacteria. Enzymes
      that are able to hydrolyze these cell membrane polymers generally play important
      roles for protecting plants and animals against infection with insects and
      pathogens. A particular group of such glycoside hydrolase enzymes share some
      common features in their three-dimensional structure and in their molecular
      mechanism, forming the lysozyme superfamily. RESULTS: Besides having a similar
      fold, all known catalytic domains of glycoside hydrolase proteins of lysozyme
      superfamily (families and subfamilies GH19, GH22, GH23, GH24 and GH46) share in
      common two structural elements: the central helix of the all-alpha domain, which
      invariably contains the catalytic glutamate residue acting as general-acid
      catalyst, and a beta-hairpin pointed towards the substrate binding cleft. The
      invariant beta-hairpin structure is interestingly found to display the highest
      amino acid conservation in aligned sequences of a given family, thereby allowing
      to define signature motifs for each GH family. Most of such signature motifs are
      found to have promising performances for searching sequence databases. Our
      structural analysis further indicates that the GH motifs participate in enzymatic
      catalysis essentially by containing the catalytic water positioning residue of
      inverting mechanism. CONCLUSIONS: The seven families and subfamilies of the
      lysozyme superfamily all have in common a beta-hairpin structure which displays a
      family-specific sequence motif. These GH beta-hairpin motifs contain potentially
      important residues for the catalytic activity, thereby suggesting the
      participation of the GH motif to catalysis and also revealing a common catalytic
      scheme utilized by enzymes of the lysozyme superfamily.

PMID- 21085706
TI  - Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of
      glucose homeostasis or insulin secretion.
AB  - BACKGROUND: Insulin secretion is a complex and highly regulated process. It is
      well established that cytoplasmic calcium is a key regulator of insulin
      secretion, but how elevated intracellular calcium triggers insulin granule
      exocytosis remains unclear, and we have only begun to define the identities of
      proteins that are responsible for sensing calcium changes and for transmitting
      the calcium signal to release machineries. Synaptotagmins are primarily expressed
      in brain and endocrine cells and exhibit diverse calcium binding properties.
      Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release
      in respective brain regions, while synaptotagmin-7 is a positive regulator of
      calcium-dependent insulin release. Unlike the three neuronal calcium sensors,
      whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion
      resulted in only partial loss of calcium-dependent insulin secretion, thus
      suggesting that other calcium-sensors must participate in the regulation of
      insulin secretion. Of the other synaptotagmin isoforms that are present in
      pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at
      the highest level after synaptotagmin-7. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study we tested whether synaptotagmin-9 participates in the regulation of glucose
      stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p
      S9X) mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in
      glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in
      vivo and from isolated islets were not affected in the p-S9X mice. Single-cell
      capacitance measurements showed no difference in insulin granule exocytosis
      between p-S9X and control mice. CONCLUSIONS: Thus, synaptotagmin-9, although a
      major calcium sensor in the brain, is not involved in the regulation of glucose
      stimulated insulin release from pancreatic beta-cells.

PMID- 21085703
TI  - The roles of the Saccharomyces cerevisiae RecQ helicase SGS1 in meiotic genome
      surveillance.
AB  - BACKGROUND: The Saccharomyces cerevisiae RecQ helicase Sgs1 is essential for
      mitotic and meiotic genome stability. The stage at which Sgs1 acts during meiosis
      is subject to debate. Cytological experiments showed that a deletion of SGS1
      leads to an increase in synapsis initiation complexes and axial associations
      leading to the proposal that it has an early role in unwinding surplus strand
      invasion events. Physical studies of recombination intermediates implicate it in
      the dissolution of double Holliday junctions between sister chromatids.
      METHODOLOGY/PRINCIPAL FINDINGS: In this work, we observed an increase in meiotic
      recombination between diverged sequences (homeologous recombination) and an
      increase in unequal sister chromatid events when SGS1 is deleted. The first of
      these observations is most consistent with an early role of Sgs1 in unwinding
      inappropriate strand invasion events while the second is consistent with
      unwinding or dissolution of recombination intermediates in an Mlh1- and Top3
      dependent manner. We also provide data that suggest that Sgs1 is involved in the
      rejection of 'second strand capture' when sequence divergence is present.
      Finally, we have identified a novel class of tetrads where non-sister spores
      (pairs of spores where each contains a centromere marker from a different parent)
      are inviable. We propose a model for this unusual pattern of viability based on
      the inability of sgs1 mutants to untangle intertwined chromosomes. Our data
      suggest that this role of Sgs1 is not dependent on its interaction with Top3. We
      propose that in the absence of SGS1 chromosomes may sometimes remain entangled at
      the end of pre-meiotic replication. This, combined with reciprocal crossing over,
      could lead to physical destruction of the recombined and entangled chromosomes.
      We hypothesise that Sgs1, acting in concert with the topoisomerase Top2, resolves
      these structures. CONCLUSIONS: This work provides evidence that Sgs1 interacts
      with various partner proteins to maintain genome stability throughout meiosis.

PMID- 21085707
TI  - Integrative analysis of low- and high-resolution eQTL.
AB  - The study of expression quantitative trait loci (eQTL) is a powerful way of
      detecting transcriptional regulators at a genomic scale and for elucidating how
      natural genetic variation impacts gene expression. Power and genetic resolution
      are heavily affected by the study population: whereas recombinant inbred (RI)
      strains yield greater statistical power with low genetic resolution, using
      diverse inbred or outbred strains improves genetic resolution at the cost of
      lower power. In order to overcome the limitations of both individual approaches,
      we combine data from RI strains with genetically more diverse strains and analyze
      hippocampus eQTL data obtained from mouse RI strains (BXD) and from a panel of
      diverse inbred strains (Mouse Diversity Panel, MDP). We perform a systematic
      analysis of the consistency of eQTL independently obtained from these two
      populations and demonstrate that a significant fraction of eQTL can be
      replicated. Based on existing knowledge from pathway databases we assess
      different approaches for using the high-resolution MDP data for fine mapping BXD
      eQTL. Finally, we apply this framework to an eQTL hotspot on chromosome 1 (Qrr1),
      which has been implicated in a range of neurological traits. Here we present the
      first systematic examination of the consistency between eQTL obtained
      independently from the BXD and MDP populations. Our analysis of fine-mapping
      approaches is based on 'real life' data as opposed to simulated data and it
      allows us to propose a strategy for using MDP data to fine map BXD eQTL.
      Application of this framework to Qrr1 reveals that this eQTL hotspot is not
      caused by just one (or few) 'master regulators', but actually by a set of
      polymorphic genes specific to the central nervous system.

PMID- 21085708
TI  - Deletion of the basement membrane heparan sulfate proteoglycan type XVIII
      collagen causes hypertriglyceridemia in mice and humans.
AB  - BACKGROUND: Lipoprotein lipase (Lpl) acts on triglyceride-rich lipoproteins in
      the peripheral circulation, liberating free fatty acids for energy metabolism or
      storage. This essential enzyme is synthesized in parenchymal cells of adipose
      tissue, heart, and skeletal muscle and migrates to the luminal side of the
      vascular endothelium where it acts upon circulating lipoproteins. Prior studies
      suggested that Lpl is immobilized by way of heparan sulfate proteoglycans on the
      endothelium, but genetically altering endothelial cell heparan sulfate had no
      effect on Lpl localization or lipolysis. The objective of this study was to
      determine if extracellular matrix proteoglycans affect Lpl distribution and
      triglyceride metabolism. METHODS AND FINDINGS: We examined mutant mice defective
      in collagen XVIII (Col18), a heparan sulfate proteoglycan present in vascular
      basement membranes. Loss of Col18 reduces plasma levels of Lpl enzyme and
      activity, which results in mild fasting hypertriglyceridemia and diet-induced
      hyperchylomicronemia. Humans with Knobloch Syndrome caused by a null mutation in
      the vascular form of Col18 also present lower than normal plasma Lpl mass and
      activity and exhibit fasting hypertriglyceridemia. CONCLUSIONS: This is the first
      report demonstrating that Lpl presentation on the lumenal side of the endothelium
      depends on a basement membrane proteoglycan and demonstrates a previously
      unrecognized phenotype in patients lacking Col18.

PMID- 21085709
TI  - Evaluation of three sampling methods to monitor outcomes of antiretroviral
      treatment programmes in low- and middle-income countries.
AB  - BACKGROUND: Retention of patients on antiretroviral therapy (ART) over time is a
      proxy for quality of care and an outcome indicator to monitor ART programs. Using
      existing databases (Antiretroviral in Lower Income Countries of the International
      Databases to Evaluate AIDS and Medecins Sans Frontieres), we evaluated three
      sampling approaches to simplify the generation of outcome indicators. METHODS AND
      FINDINGS: We used individual patient data from 27 ART sites and included 27,201
      ART-naive adults (>=15 years) who initiated ART in 2005. For each site, we
      generated two outcome indicators at 12 months, retention on ART and proportion of
      patients lost to follow-up (LFU), first using all patient data and then within a
      smaller group of patients selected using three sampling methods (random,
      systematic and consecutive sampling). For each method and each site, 500 samples
      were generated, and the average result was compared with the unsampled value. The
      95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th)
      percentile values from the 500 samples. Overall, retention on ART was 76.5%
      (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9).
      Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for
      random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the
      consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6
      14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive
      sampling, 50% of sites had SD within +/-5% of the unsampled site value.
      CONCLUSIONS: Our results suggest that random, systematic or consecutive sampling
      methods are feasible for monitoring ART indicators at national level. However,
      sampling may not produce precise estimates in some sites.

PMID- 21085710
TI  - Optimizing topological cascade resilience based on the structure of terrorist
      networks.
AB  - Complex socioeconomic networks such as information, finance and even terrorist
      networks need resilience to cascades--to prevent the failure of a single node
      from causing a far-reaching domino effect. We show that terrorist and guerrilla
      networks are uniquely cascade-resilient while maintaining high efficiency, but
      they become more vulnerable beyond a certain threshold. We also introduce an
      optimization method for constructing networks with high passive cascade
      resilience. The optimal networks are found to be based on cells, where each cell
      has a star topology. Counterintuitively, we find that there are conditions where
      networks should not be modified to stop cascades because doing so would come at a
      disproportionate loss of efficiency. Implementation of these findings can lead to
      more cascade-resilient networks in many diverse areas.

PMID- 21085711
TI  - Barriers to insecticide-treated mosquito net possession 2 years after a mass free
      distribution campaign in Luangwa District, Zambia.
AB  - BACKGROUND AND METHODS: Roll Back Malaria set the goal of 100% of households in
      malaria endemic countries in Africa owning an insecticide-treated mosquito net
      (ITN) by 2010. Zambia has used mass free distribution campaigns and distribution
      through antenatal care (ANC) clinics to achieve high coverage. METHODOLOGY AND
      PRINCIPAL FINDINGS: We conducted a probability survey of 801 households in 2008
      to assess factors associated with households that lacked an ITN after mass
      distribution. Community perceptions of barriers to ITN access were also obtained
      from in-depth interviews with household heads that reported not owning an ITN.
      Nearly 74% of households in Luangwa district reported owning >=1 ITN. Logistic
      regression showed households without a child <5 years old during the ITN
      distribution campaigns were twice as likely to not have an ITN as those with a
      child <5 during distribution (Adjusted odds ratio (AOR)  = 2.43; 95% confidence
      interval (CI): 1.67-3.55). Households without a woman who attended an ANC in the
      past 2 years were more likely to be without ITNs compared to households with a
      woman who attended an ANC in the past 2 years (AOR  = 1.52; 95% CI: 1.04-2.21).
      In-depth interviews with heads of households without an ITN revealed that old age
      was a perceived barrier to receiving an ITN during distribution, and that ITNs
      wore out before they could be replaced. CONCLUSIONS AND SIGNIFICANCE: Delivery of
      a large number of ITNs does not translate directly into 100% household coverage.
      Due to their design, current ITN distribution strategies may miss households
      occupied by the elderly and those without children or ANC access. ITN
      distribution strategies targeting the elderly, those with limited access to
      distribution points, and others most likely to be missed are necessary if 100%
      ITN coverage of households is to be achieved.

PMID- 21085712
TI  - Indirect comparisons: a review of reporting and methodological quality.
AB  - BACKGROUND: The indirect comparison of two interventions can be valuable in many
      situations. However, the quality of an indirect comparison will depend on several
      factors including the chosen methodology and validity of underlying assumptions.
      Published indirect comparisons are increasingly more common in the medical
      literature, but as yet, there are no published recommendations of how they should
      be reported. Our aim is to systematically review the quality of published
      indirect comparisons to add to existing empirical data suggesting that
      improvements can be made when reporting and applying indirect comparisons.
      METHODOLOGY/FINDINGS: Reviews applying statistical methods to indirectly compare
      the clinical effectiveness of two interventions using randomised controlled
      trials were eligible. We searched (1966-2008) Database of Abstracts and Reviews
      of Effects, The Cochrane library, and Medline. Full review publications were
      assessed for eligibility. Specific criteria to assess quality were developed and
      applied. Forty-three reviews were included. Adequate methodology was used to
      calculate the indirect comparison in 41 reviews. Nineteen reviews assessed the
      similarity assumption using sensitivity analysis, subgroup analysis, or meta
      regression. Eleven reviews compared trial-level characteristics. Twenty-four
      reviews assessed statistical homogeneity. Twelve reviews investigated causes of
      heterogeneity. Seventeen reviews included direct and indirect evidence for the
      same comparison; six reviews assessed consistency. One review combined both
      evidence types. Twenty-five reviews urged caution in interpretation of results,
      and 24 reviews indicated when results were from indirect evidence by stating this
      term with the result. CONCLUSIONS: This review shows that the underlying
      assumptions are not routinely explored or reported when undertaking indirect
      comparisons. We recommend, therefore, that the quality of indirect comparisons
      should be improved, in particular, by assessing assumptions and reporting the
      assessment methods applied. We propose that the quality criteria applied in this
      article may provide a basis to help review authors carry out indirect comparisons
      and to aid appropriate interpretation.

PMID- 21085713
TI  - Localization of secondary metabolites in marine invertebrates: contribution of
      MALDI MSI for the study of saponins in Cuvierian tubules of H. forskali.
AB  - BACKGROUND: Several species of sea cucumbers of the family Holothuriidae possess
      a particular mechanical defense system called the Cuvierian tubules (Ct). It is
      also a chemical defense system as triterpene glycosides (saponins) appear to be
      particularly concentrated in Ct. In the present study, the precise localization
      of saponins in the Ct of Holothuria forskali is investigated. Classical
      histochemical labeling using lectin was firstly performed but did not generate
      any conclusive results. Thus, MALDI mass spectrometry Imaging (MALDI-MSI) was
      directly applied and completed by statistical multivariate tests. A comparison
      between the tubules of relaxed and stressed animals was realized. RESULTS: These
      analyses allowed the detection of three groups of ions, corresponding to the
      isomeric saponins of the tubules. Saponins detected at m/z 1287 and 1303 were the
      most abundant and were apparently localized in the connective tissue of the
      tubules of both relaxed and stressed individuals. Saponins at m/z 1125 and 1141
      were detected in lower amount and were present in tissues of relaxed animals.
      Finally, saponin ions at 1433, 1449, 1463 and 1479 were observed in some Ct of
      stressed holothuroids in the outer part of the connective tissue. The saponin
      group m/z 14xx seems therefore to be stress-specific and could originate from
      modifications of the saponins with m/z of 11xx. CONCLUSIONS: All the results
      taken together indicate a complex chemical defense mechanism with, for a single
      organ, different sets of saponins originating from different cell populations and
      presenting different responses to stress. The present study also reflects that
      MALDI-MSI is a valuable tool for chemical ecology studies in which specific
      chemical signalling molecules like allelochemicals or pheromones have to be
      tracked. This report represents one of the very first studies using these tools
      to provide a functional and ecological understanding of the role of natural
      products from marine invertebrates.

PMID- 21085714
TI  - Double subgenomic alphaviruses expressing multiple fluorescent proteins using a
      Rhopalosiphum padi virus internal ribosome entry site element.
AB  - Double subgenomic Sindbis virus (dsSINV) vectors are widely used for the
      expression of proteins, peptides, and RNA sequences. These recombinant RNA
      viruses permit high level expression of a heterologous sequence in a wide range
      of animals, tissues, and cells. However, the alphavirus genome structure and
      replication strategy is not readily amenable to the expression of more than one
      heterologous sequence. The Rhopalosiphum padi virus (RhPV) genome contains two
      internal ribosome entry site (IRES) elements that mediate cap-independent
      translation of the virus nonstructural and structural proteins. Most IRES
      elements that have been characterized function only in mammalian cells but
      previous work has shown that the IRES element present in the 5' untranslated
      region (UTR) of the RhPV genome functions efficiently in mammalian, insect, and
      plant systems. To determine if the 5' RhPV IRES element could be used to express
      more than one heterologous sequence from a dsSINV vector, RhPV 5' IRES sequences
      were placed between genes for two different fluorescent marker proteins in the
      dsSINV, TE/3'2J/mcs. While mammalian and insect cells infected with recombinant
      viruses containing the RhPV sequences expressed both fluorescent marker proteins,
      only single marker proteins were routinely observed in cells infected with dsSINV
      vectors in which the RhPV IRES had been replaced by a luciferase fragment, an
      antisense RhPV IRES, or no intergenic sequence. Thus, we report development of a
      versatile tool for the expression of multiple sequences in diverse cell types.

PMID- 21085715
TI  - Water quality and herbivory interactively drive coral-reef recovery patterns in
      American Samoa.
AB  - BACKGROUND: Compared with a wealth of information regarding coral-reef recovery
      patterns following major disturbances, less insight exists to explain the
      cause(s) of spatial variation in the recovery process. METHODOLOGY/PRINCIPAL
      FINDINGS: This study quantifies the influence of herbivory and water quality upon
      coral reef assemblages through space and time in Tutuila, American Samoa, a
      Pacific high island. Widespread declines in dominant corals (Acropora and
      Montipora) resulted from cyclone Heta at the end of 2003, shortly after the study
      began. Four sites that initially had similar coral reef assemblages but
      differential temporal dynamics four years following the disturbance event were
      classified by standardized measures of 'recovery status', defined by rates of
      change in ecological measures that are known to be sensitive to localized
      stressors. Status was best predicted, interactively, by water quality and
      herbivory. Expanding upon temporal trends, this study examined if similar
      dependencies existed through space; building multiple regression models to
      identify linkages between similar status measures and local stressors for 17
      localities around Tutuila. The results highlighted consistent, interactive
      interdependencies for coral reef assemblages residing upon two unique geological
      reef types. Finally, the predictive regression models produced at the island
      scale were graphically interpreted with respect to hypothesized site-specific
      recovery thresholds. CONCLUSIONS/SIGNIFICANCE: Cumulatively, our study purports
      that moving away from describing relatively well-known patterns behind recovery,
      and focusing upon understanding causes, improves our foundation to predict future
      ecological dynamics, and thus improves coral reef management.

PMID- 21085716
TI  - Behaviour and physiology: the thermal strategy of leatherback turtles.
AB  - BACKGROUND: Adult leatherback turtles (Dermochelys coriacea) exhibit thermal
      gradients between their bodies and the environment of >=8 degrees C in sub-polar
      waters and <=4 degrees C in the tropics. There has been no direct evidence for
      thermoregulation in leatherbacks although modelling and morphological studies
      have given an indication of how thermoregulation may be achieved.
      METHODOLOGY/PRINCIPAL FINDINGS: We show for the first time that leatherbacks are
      indeed capable of thermoregulation from studies on juvenile leatherbacks of 16
      and 37 kg. In cold water (< 25 degrees C), flipper stroke frequency increased,
      heat loss through the plastron, carapace and flippers was minimized, and a
      positive thermal gradient of up to 2.3 degrees C was maintained between body and
      environment. In warm water (25 - 31 degrees C), turtles were inactive and heat
      loss through their plastron, carapace and flippers increased. The thermal
      gradient was minimized (0.5 degrees C). Using a scaling model, we estimate that a
      300 kg adult leatherback is able to maintain a maximum thermal gradient of 18.2
      degrees C in cold sub-polar waters. CONCLUSIONS/SIGNIFICANCE: In juvenile
      leatherbacks, heat gain is controlled behaviourally by increasing activity while
      heat flux is regulated physiologically, presumably by regulation of blood flow
      distribution. Hence, harnessing physiology and behaviour allows leatherbacks to
      keep warm while foraging in cold sub-polar waters and to prevent overheating in a
      tropical environment.

PMID- 21085718
TI  - Controlled pore formation in organotrialkoxysilane-derived hybrids: from aerogels
      to hierarchically porous monoliths.
AB  - Porous polysilsesquioxane gels derived from sol-gel systems based on
      trifunctional silanes are reviewed. Although it is well known that trifunctional
      silanes possess inherent difficulties in forming homogeneous gels, increasing
      attention is being paid on these precursors and resultant porous
      polysilsesquioxanes because of hydrophobicity, functionality, and versatile
      mechanical properties. Much effort has been made to overcome the difficulties for
      homogeneous gelation, and a number of excellent porous materials with various
      pore properties have been explored. In this critical review, we put special
      emphasis on the formation of a well-defined macroporous structure by making use
      of phase separation, which in turn is a serious problem in obtaining homogeneous
      gels though. Porous polysilsesquioxane monoliths with the hierarchical structure
      and transparent aerogels with high mechanical durability are particularly
      highlighted (169 references).

PMID- 21085717
TI  - Contrasting genetic structure in two co-distributed species of old world fruit
      bat.
AB  - The fulvous fruit bat (Rousettus leschenaulti) and the greater short-nosed fruit
      bat (Cynopterus sphinx) are two abundant and widely co-distributed Old World
      fruit bats in Southeast and East Asia. The former species forms large colonies in
      caves while the latter roots in small groups in trees. To test whether these
      differences in social organization and roosting ecology are associated with
      contrasting patterns of gene flow, we used mtDNA and nuclear loci to characterize
      population genetic subdivision and phylogeographic histories in both species
      sampled from China, Vietnam and India. Our analyses from R. leschenaulti using
      both types of marker revealed little evidence of genetic structure across the
      study region. On the other hand, C. sphinx showed significant genetic mtDNA
      differentiation between the samples from India compared with China and Vietnam,
      as well as greater structuring of microsatellite genotypes within China.
      Demographic analyses indicated signatures of past rapid population expansion in
      both taxa, with more recent demographic growth in C. sphinx. Therefore, the
      relative genetic homogeneity in R. leschenaulti is unlikely to reflect past
      events. Instead we suggest that the absence of substructure in R. leschenaulti is
      a consequence of higher levels of gene flow among colonies, and that greater
      vagility in this species is an adaptation associated with cave roosting.

PMID- 21085719
TI  - Practical approach for macroporous structure embedded microfluidic system and the
      catalytic microchemical application.
AB  - We present a low cost and practical approach to integrate 3D ordered macroporous
      polyfluoropolyether (PFPE) patterns into a microchannel by a series of porous
      pattern fabrication processes and subsequent photolithography in a site- and
      shape-selective manner. The 3D ordered macroporous patterns with high-resolution
      edges were firstly fabricated by microtransfer molding (MU-TM) of the sacrificial
      polystyrene (PS) template infiltrated with PFPE as a non-adhesive and solvent
      resistant skeletal material. The resulting robust PFPE porous structures with
      high solvent resistance on a silicon wafer can easily be embedded into the
      microchannel with the aid of conventional photolithography, leading to a
      microfluidic system with a built-in microstructure. Moreover, catalytic Pd
      nanoparticles implanted on the surface of the porous structure were obtained by
      use of Pd nanoparticle deposited PS spheres, the porous structure embedded
      channel was utilized to perform a Suzuki coupling reaction.

PMID- 21085720
TI  - Highly diastereroselective synthesis of dihydrofurans and dihydropyrroles via
      pyridine catalyzed formal [4+1] annulation.
AB  - A pyridine-catalyzed ylide cyclization affording dihydrofurans and
      dihydropyrroles has been developed. In the presence of a catalytic amount of
      pyridine and Fe(Tcpp)Cl, alpha-ylidene-beta-diketones and alpha,beta-unsaturated
      imines react with diazoacetates providing dihydrofurans and dihydropyrroles
      respectively, in up to 96% yield with high diastereoselectivities.

PMID- 21085721
TI  - Copper proteomes, phylogenetics and evolution.
AB  - This paper is a continuation of our study of the connection between the changing
      environment and the changing use of particular elements in organisms in the
      course of their combined evolution (Decaria, Bertini and Williams, Metallomics,
      2010, 2, 706). Here we treat the changes in copper proteins in historically the
      same increasingly oxidising environmental conditions. The study is a
      bioinformatic analysis of the types and the numbers of copper domains of proteins
      from 435 DNA sequences of a wide range of organisms available in NCBI, using the
      method developed by Andreini, Bertini and Rosato in Accounts of Chemical Research
      2009, 42, 1471. The copper domains of greatest interest are found predominantly
      in copper chaperones, homeostatic proteins and redox enzymes mainly used outside
      the cytoplasm which are in themselves somewhat diverse. The multiplicity of these
      proteins is strongly marked. The contrasting use of the iron and heme iron
      proteins in oxidations, mostly in the cytoplasm, is compared with them and with
      activity of zinc fingers during evolution. It is shown that evolution is a
      coordinated development of the chemistry of elements with use of novel and
      multiple copies of their proteins as their availability rises in the environment.

PMID- 21085722
TI  - Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct.
AB  - The accumulation and cytotoxicity of a 10 MUmol L-1 equimolar human serum albumin
      cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor
      Cells (EATC) and adherent Ehrlich Lettre Ascites Cells (Lettre). HSA-Pt did not
      induce apoptosis nor was it taken up by the cells to any significant amount
      within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared
      to 10 MUmol L-1 cisplatin for which a larger accumulation and cytotoxicity were
      observed in EATC compared to Lettre. The experiment was performed with cell
      medium exchange every fourth hour as HSA-Pt and cisplatin were not stable in RPMI
      1640 with 10% serum. The stability was determined using size exclusion
      chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and
      after 4 h new platinum peaks were observed. These findings indicate that before
      conducting cell experiments, the stability of the compound in the cell medium
      should be investigated especially when long exposure times are applied.
      Furthermore, HSA-Pt was found to be stable in Hanks Balanced Saline Solution
      (HBSS) and in Phosphate Buffered Saline (PBS) at pH 5.3, 6.1 and 7.4. Thus, the
      shift in pH when HSA-cisplatin passes from blood (pH 7.4) to tumor tissue (pH 5
      6) is not capable of releasing cisplatin from HSA.

PMID- 21085723
TI  - Titania supported gold nanoparticles as photocatalyst.
AB  - This Perspective is focused on the photocatalytic activity of gold nanoparticles
      supported on titania (Au/TiO(2)). Titania is the most widely used photocatalyst,
      but its limited activity under visible light irradiation has motivated the quest
      for modified titania materials absorbing visible light. The review starts by
      justifying how doping with metallic elements is a related strategy, but
      different, to that leading to the use of Au/TiO(2) in photocatalysis. Data
      supporting and confirming the photoactivity of gold nanoparticles in colloidal
      solutions are briefly presented to justify the possibility of gold
      photosensitization of titania by electron injection into the conduction band.
      After describing the most common procedures used to prepare Au/TiO(2), the
      central part of this article is focused on the photocatalytic activity reported
      for Au/TiO(2) for hydrogen generation, dye decoloration, phenol decomposition and
      carboxylic acid degradation, among other processes. Emphasis is given to the role
      that parameters like Au loading, particle size, surface area, spatial structuring
      and others play on the photocatalytic activity. One important issue has been to
      distinguish those reports using visible light from those other in which direct
      titania excitation by UV light has been used. These Au/TiO(2) photocatalysts can
      find real applications in the near future for environmental remediation and for
      hydrogen generation.

PMID- 21085724
TI  - Reactions of in situ generated hydrated organotin cations with chelating O,O- or
      O,N-ligands: a possible structure-directing influence of the organic substituent
      on tin.
AB  - The reaction of [n-Bu(2)SnO](n) with 1,5-naphthalenedisulfonic acid tetrahydrate
      in a 1:1 stoichiometry followed by reaction with 2,2'-bipyridine-N,N'-dioxide
      (BPDO-I) afforded a 1D-coordination polymer [n-Bu(2)Sn(BPDO-I)(1,5
      C(10)H(6)(SO(3))(2))](n) (1) where the disulfonate ligand acts as a bridging
      ligand between two tin centers. An analogous reaction involving [Ph(2)SnO](n)
      afforded a trihydrated O,O'-chelated diorganotin cation [{Ph(2)Sn(BPDO
      I)(H(2)O)(3)}(2+)][C(10)H(6)(SO(3)(-))(2)].2CH(3)OH (2.2CH(3)OH). Utilizing two
      equivalents of BPDO-I in this reaction resulted in the ionic complex
      [{Ph(2)Sn(BPDO-I)(2)(H(2)O)}(2+)][C(10)H(6)(SO(3)(-))(2)].3H(2)O (3.3H(2)O). In 2
      and 3 the sulfonate ligands are not present in the coordination sphere of tin.
      Reaction of [n-Bu(2)SnO](n) and 1,5-naphthalenedisulfonic acid tetrahydrate,
      followed by reaction with [bis(diphenylphosphoryl)methane (DPPOM)] resulted in
      the formation of, [{n-Bu(2)Sn(DPPOM)(2)(H(2)O)(1,5-C(10)H(6)(SO(3))(SO(3)(
      ))}].H(2)O (4.H(2)O). Of the two coordinating groups present in DPPOM, only one
      P=O group is coordinated to the tin atom. The remaining P=O motif is free and is
      involved in intramolecular H-bonding with the tin-bound water molecule. Using
      [Ph(2)SnO](n) instead of [n-Bu(2)SnO](n) afforded the ionic complex
      [{Ph(2)Sn(DPPOM)(2)}(2+){1,5-C(10)H(6)(SO(3)(-))(2)}] (5) where the DPPOM
      functions as a chelating ligand. The reaction of [n-Bu(2)SnO](n) with 1,5
      naphthalenedisulfonic acid tetrahydrate followed by addition of one equivalent of
      8-hydroxyquinoline (8-HQ) in presence of triethylamine afforded the neutral
      dinuclear complex, [(H(2)O)(8-Q)n-Bu(2)Sn(MU-1,5-C(10)H(6)(SO(3))(2))n-Bu(2)Sn(8
      Q)(H(2)O)] (6) where the two tin atoms are bridged by the disulfonate ligand.
      Compounds 1-6 are thermally stable as shown by their thermogravimetric analyses.

PMID- 21085725
TI  - Direct conversion of methane to higher hydrocarbons using AlBr3-HBr superacid
      catalyst.
AB  - The direct gas phase catalytic oligomerization of methane at temperatures <=673 K
      has been demonstrated using AlBr(3)-HBr superacid. The reaction produces C(2)+
      hydrocarbons and hydrogen in a single step at 1 atm in a continuous flow reactor
      at a nominal residence time of 60 s. The essentially complete conversion of
      methane appears to be due to protolytic activation of methane in the presence of
      H(+)AlBr(4)(-).

PMID- 21085726
TI  - Mechanically interlocked molecular architectures functionalised with fullerenes.
AB  - The combination of fullerenes and mechanically interlocked molecular
      architectures has opened up a new field of research. A selection of
      representative examples of mechanically interlocked molecules functionalised with
      fullerenes are discussed here.

PMID- 21085727
TI  - Mechanistic investigation of organolanthanide-mediated hydroamination of
      aminoallenes: a comprehensive computational assessment of various routes for
      allene activation.
AB  - The present mechanistic study comprehensively explores alternative scenarios for
      activation of the amine-linked allene C=C linkage toward nucleophilic amido
      attack in the intramolecular hydroamination of a prototypical 1,3-disubstituted
      aminoallene by a well-characterised samarocene-amido catalyst. Firstly, the non
      insertive mechanism by Scott featuring C-N ring closure with concomitant amino
      proton delivery onto the allene unit has been explored and its key features have
      been defined. This scenario has been compared and contrasted with the classical
      stepwise Ln-N sigma-bond insertive mechanism that involves rapid substrate
      association/dissociation equilibria for the Ln-amido-substrate resting state and
      also for Ln-azacycle intermediates, facile and reversible exocyclic ring closure
      through migratory allene insertion into the Ln-N amido sigma-bond, linked to
      turnover-limiting Ln-C azacycle aminolysis. The Ln-N sigma-bond insertive
      mechanism prevails for the studied intramolecular hydroamination of 4,5-heptadien
      1-ylamine 1 by [Cp*(2)Sm-CH(TMS)(2)] starting material 2. The following aspects
      are in support of this mechanism: 1) the derived rate law is consistent with the
      observed empirical rate law; 2) the assessed effective barrier for turnover
      limiting aminolysis does agree reasonably well with empirically determined Eyring
      parameters; 3) the ring-tether double bond selectivity is consistently
      elucidated. On the other hand, this study reveals that the non-insertive
      mechanism, which features a prohibitively large barrier, is unachievable. Spatial
      demands around the lanthanide centre effect the two mechanisms differently. A
      sufficiently accessible lanthanide is a crucial requirement of the Ln-N sigma
      bond insertive mechanism and enhanced encumbrance renders the cyclisation step
      less accessible kinetically. This contrasts with the non-insertive mechanism,
      where greater lanthanide protection has a rather modest influence. The present
      study indicates that the non-insertive mechanism would prevail if the lanthanide
      centre were to be protected effectively against C=C bond approach, whilst
      ensuring a high polarity of the Ln-N sigma-bond together with a sufficiently
      acidic amino proton.

PMID- 21085728
TI  - Structural and mechanistic information on the nitrosation of model Fe(II)
      complexes containing a biomimetic S4N chelate.
AB  - In order to provide insight into the reaction pathways of nitrogen oxide redox
      species with [Fe-S] models that may parallel those existing in biology, the
      reactivity of the iron-sulfur species, {[Fe(II)(S(4)NEt(2)N)]}(2) (1) and
      [Fe(II)(CH(3)CN)(S(4)NEt(2)N)] (2), where (S(4)NEt(2)N)(2-) = 2,6-bis(2
      mercaptophenylthiomethyl)-4-diethylaminopyridine(2-), towards NO(+) (nitrosation)
      has been studied mechanistically in acetonitrile and compared with the
      corresponding reactions with NO (nitrosylation). For the nitrosation of 1, the
      reaction takes place in two steps that correspond to the nitrosation of the
      mononuclear (2) and dinuclear (1) complexes, respectively. For the corresponding
      carbonyl complex [Fe(II)(CO)(S(4)NEt(2)N)] (3), the nitrosation reaction occurs
      in a single step. The relative reactivity of the iron-sulfur species is
      approximately (1)/(2)/(3) = 1/20/10. Activation parameters for the nitrosation of
      1 (DeltaH(#) = 27 +/- 1 kJ mol(-1), DeltaS(#) = -111 +/- 2 J K(-1) mol(-1), and
      DeltaV(#) = -19 +/- 2 cm(3) mol(-1)), 2 (DeltaH(#) = 46 +/- 2 kJ mol(-1),
      DeltaS(#) = -22 +/- 7 J K(-1) mol(-1), and DeltaV(#) = -9.7 +/- 0.4 cm(3) mol(
      1)) and 3 (DeltaH(#) = 38 +/- 1 kJ mol(-1), DeltaS(#) = -44 +/- 4 J K(-1) mol(
      1), and DeltaV(#) = -7.8 +/- 0.3 cm(3) mol(-1)) were determined from variable
      temperature and pressure studies. The significantly negative DeltaS(#) and
      DeltaV(#) values found for the nitrosation reactions are consistent with an
      associative mechanism. A comparative study of the reactivity of the iron-sulfur
      species 1 to 3 towards NO(+) and NO is presented.

PMID- 21085729
TI  - Agostic or not? Detailed Density Functional Theory studies of the compounds
      [LRh(CO)Cl], [LRh(COD)Cl] and [LRhCl] (L = cyclic (alkyl)(amino)carbene, COD =
      cyclooctadiene).
AB  - Detailed Density Functional Theory (DFT) studies were conducted on the rhodium
      compounds [LRh(CO)Cl] (1), [LRhCl] (2) and [LRh(COD)Cl] (3) (L = cyclic
      (alkyl)(amino)carbene, CAAC; COD = cyclooctadiene). Particular attention was paid
      to the two cyclohexyl hydrogens of the CAAC which are in close proximity to the
      metal centre. Bader and NBO analyses confirmed an agostic interaction, and NBO
      analysis revealed that in the case of 1, the Rh-CO antibonding orbital acts as an
      acceptor. Removal of the CO ligand (2) did not significantly change the agostic
      interaction of the two cyclohexyl hydrogens or the geometry of the cyclohexyl
      ligand. Replacement of the 2e(-) donor CO with the 4e(-) donor COD gives a
      different picture. Although both cyclohexyl hydrogens are still in close
      proximity to the metal centre, neither are agostically bound to it. In fact, the
      very weak interaction of one of them is of the same order as that present in the
      Cl-H bond. We thus suggest a revised description of agostic bonding.

PMID- 21085730
TI  - Suppression of statin effectiveness by copper and zinc in yeast and human cells.
AB  - Lovastatin and other statins inhibit HMG-CoA reductase, which carries out an
      early step in the sterol biosynthesis pathway. Statins lower cholesterol and are
      widely prescribed to prevent heart disease, but like many drugs, they can
      interact with nutritionally acquired metabolites. To probe these interactions, we
      explored the effect of a diverse library of metabolites on statin effectiveness
      using a Saccharomyces cerevisiae model. In yeast, treatment with lovastatin
      results in reduced growth. We combined lovastatin with the library of
      metabolites, and found that copper and zinc ions impaired the ability of the
      statin to inhibit yeast growth. Using an integrated genomic and metabolomic
      approach, we found that lovastatin plus metal synergistically upregulated some
      sterol biosynthesis genes. This altered pattern of gene expression resulted in
      greater flux through the sterol biosynthesis pathway and an increase in
      ergosterol levels. Each sterol intermediate level was correlated with expression
      of the upstream gene. Thus, the ergosterol biosynthetic response induced by
      statin is enhanced by copper and zinc. In cultured mammalian cells, these metals
      also rescued statin growth inhibition. Because copper and zinc impair the ability
      of statin to reduce sterol biosynthesis, dietary intake of these metals could
      have clinical relevance for statin treatment in humans.

PMID- 21085732
TI  - Understanding the role of the flexible bridging linker through kinetics and
      mechanistic study of Pt(II) amphiphiles derived from a bis(2-pyridylmethyl)amine
      chelate head group.
AB  - The substitution of aqua ligands of mononuclear Pt(II) complexes of the general
      form [Pt(H(2)O)(N,N-bis(2-pyridylmethyl)-N(CH(2))(n)-CH(3); -NC(CH(3))(3); 
      NH](CF(3)SO(3))(2), n = 1 (bpea); 2 (bppa); 3 (bpba); 5 (bpha), 9 (bpda) 
      NC(CH(3))(3) (bpbta) and -NH (bpma) by thiourea nucleophiles was investigated
      under pseudo first-order conditions as a function of concentration and
      temperature using the stopped-flow technique and UV-vis spectroscopy. The
      substitution reactions occur via two separate reaction steps, each fitting to a
      single exponential curve. In the two reaction steps, the thiourea nucleophiles
      first substitute the coordinated aqua ligand followed by ring opening via
      dechelation of one of the pyridyl units. The mode of activation for both steps
      remains associative in nature and the observed rate constants can be fitted to
      the equation k(obs(1st/2nd)) = k(2(1st/2nd))[Nu]. Appending a primary alkyl
      hydrocarbon group on the trans-N donor atom of the chelate head group marginally
      increases the rate of substitution of the aqua leaving group due to the weaker
      trans-influence of its alkyl amine donor group. However, when a tert-butyl group
      is the pendant group, reactivity increases by a factor of about two, reiterating
      the inductive nature of the flow of electron density from the tailing groups
      towards the Pt(II) metal centres. A comparison of the reactivities of the studied
      complexes with their dinuclear analogues bridged by alkyl diamines has
      demonstrated that the electronic effect of the alkyl diamine bridge on the
      overall reactivity of the multinuclear Pt(II) complexes is weak and insignificant
      when compared to steric effects due to the constraining bridge.

PMID- 21085731
TI  - Multiplexed evaluation of capture agent binding kinetics using arrays of silicon
      photonic microring resonators.
AB  - High affinity capture agents recognizing biomolecular targets are essential in
      the performance of many proteomic detection methods. Herein, we report the
      application of a label-free silicon photonic biomolecular analysis platform for
      simultaneously determining kinetic association and dissociation constants for two
      representative protein capture agents: a thrombin-binding DNA aptamer and an anti
      thrombin monoclonal antibody. The scalability and inherent multiplexing
      capability of the technology make it an attractive platform for simultaneously
      evaluating the binding characteristics of multiple capture agents recognizing the
      same target antigen, and thus a tool complementary to emerging high-throughput
      capture agent generation strategies.

PMID- 21085733
TI  - Tuning the conversion of cyclohexane into cyclohexanol/one by molecular dioxygen,
      protons and reducing agents at a single non-porphyrinic iron centre and chemical
      versatility of the tris(2-pyridylmethyl)amine TPAFe(II)Cl2 complex in mild
      oxidation chemistry.
AB  - We report that the oxygen sensitivity of some Fe(II) complexes with tripodal
      ligands can be used, with benefit, in the oxidation of cyclohexane under mild
      conditions. Depending on the solvent, two very different reaction pathways are
      involved, which share the coordination of O(2) to the metal as the common initial
      step. We have synthesized a series of alpha-chlorinated tripods in the tris(2
      pyridylmethyl)amine series Cl(n)TPA (n = 1-3) and fully characterized the
      corresponding FeX(2) complexes (X = Cl, CF(3)SO(3)). The single-crystal X-ray
      structure analyses of the FeCl(2) complexes are reported. In CH(3)CN, the FeCl(2)
      complexes react smoothly with O(2), whereas the Fe(CF(3)SO(3))(2) complexes are
      non-sensitive. In CH(3)CN, the reaction of the oxygen-sensitive Cl(n)TPAFeCl(2)
      (n = 0-3) with O(2), acetic acid and zinc amalgam, in the presence of
      cyclohexane, affords a mixture of cyclohexanol/one in an ~ ol/one ratio of 3.1
      and a selectivity of the C3 degrees /C2 degrees  in the adamantane conversion
      that is consistent with a metal-oxo based oxidation. Limited efficiency (~ 2 TON)
      was observed for the parent TPAFeCl(2) complex and Cl(1)TPAFeCl(2), whereas both
      other complexes turned out to be poorly active. The TPAFeCl(2) complex was used
      to address mechanistic questions: when the reaction was carried out in pyridine,
      the ol/one ratio shifted to 0.15 while efficiency was improved by 7-fold. In
      pyridine and in the presence of a spin trap (DMPO), the radical-based character
      of the reaction was definitely established, by contrast with acetonitrile, where
      no oxygenated radicals were detected. Thus, the reactivity differences arise from
      involvement of two distinct active species. The dichotomous radical/biomimetic
      pathway is discussed to interpret these results.

PMID- 21085734
TI  - N-heterocyclic carbene tethered amido complexes of palladium and platinum.
AB  - With a view to applications in bifunctional catalysis, a modular cross-coupling
      strategy has been used to prepare amine bis(imidazolium) salts (3a and 3b) and an
      amine mono(imidazolium) salt (6) as precursors to chelating amido-NHC ligands.
      Treating the pro-ligands 3 with 3 equivalents of the bulky base KHMDS and
      Pd(OAc)(2) or PtCl(2)(COD) gave the four amido bis(N-heterocyclic carbene) pincer
      complexes [CNC-R]M-I [M = Pd (7) or Pt (8); R = i-Pr (a) or n-Bu (b)], including
      the first examples of platinum complexes of a CNC ligand. The reaction of 7a with
      AgOTf in pyridine gave the cationic complex {[CNC-i-Pr]Pd-py}OTf (9a). Heating a
      mixture of amine mono(imidazolium) salt 6 with PdCl(2) or K(2)PtCl(4), K(2)CO(3)
      and KI in pyridine at 100  degrees C gave the complexes [C,NH]MI(2)py [M = Pd
      (10) or Pt (11)], in which the amine arm of the NHC ligand is not deprotonated
      and does not coordinate to the metal. For a solution of 10 in 1,4-dioxane,
      deprotonation of the amine occurred in a biphasic reaction with aqueous KOH at 40
      degrees C, giving the dimeric amido complex {[C,N]Pd(MU-OH)}(2) (12). The more
      inert Pt analogue 11 was unreactive under the same conditions. Solid-state
      structures of the complexes 7a, 7b, 9a, 10, 11 and 12 have been determined by
      single crystal X-ray diffraction.

PMID- 21085735
TI  - A general route to synthesize supported isolated oxide and mixed-oxide
      nanoclusters at sizes below 5 nm.
AB  - A simple and efficient route to prepare supported nanocrystalline oxides is
      presented. The synthesis procedure, i.e. in situ autocombustion of a glycine
      complex, allows the production of nanocrystals in a porous matrix presenting
      larger pore size. An example of successful formation of 2-5 nm nanocrystals is
      given for a single oxide (Fe(2)O(3)), a mixed-oxide structure (LaCoO(3)
      perovskite-type) and a nickel-doped oxide.

PMID- 21085736
TI  - Design, engineering and utility of biotic games.
AB  - Games are a significant and defining part of human culture, and their utility
      beyond pure entertainment has been demonstrated with so-called 'serious games'.
      Biotechnology--despite its recent advancements--has had no impact on gaming yet.
      Here we propose the concept of 'biotic games', i.e., games that operate on
      biological processes. Utilizing a variety of biological processes we designed and
      tested a collection of games: 'Enlightenment', 'Ciliaball', 'PAC-mecium',
      'Microbash', 'Biotic Pinball', 'POND PONG', 'PolymerRace', and 'The Prisoner's
      Smellemma'. We found that biotic games exhibit unique features compared to
      existing game modalities, such as utilizing biological noise, providing a real
      life experience rather than virtual reality, and integrating the chemical senses
      into play. Analogous to video games, biotic games could have significant
      conceptual and cost-reducing effects on biotechnology and eventually healthcare;
      enable volunteers to participate in crowd-sourcing to support medical research;
      and educate society at large to support personal medical decisions and the public
      discourse on bio-related issues.

PMID- 21085738
TI  - Computational and experimental investigations of mono-septanoside binding by
      Concanavalin A: correlation of ligand stereochemistry to enthalpies of binding.
AB  - Structure-energy relationships for a small group of pyranose and septanose mono
      saccharide ligands are developed for binding to Concanavalin A (ConA). The
      affinity of ConA for methyl "manno"beta-septanoside 7 was found to be higher than
      any of the previously reported mono-septanoside ligands. Isothermal titration
      calorimetry (ITC) in conjunction with docking simulations and quantum
      mechanics/molecular mechanics (QM/MM) modeling established the specific role of
      binding enthalpy in the structure-energy relations of ConA bound to natural mono
      saccharides and unnatural mono-septanosides. An important aspect in the
      differential binding among ligands is the deformation energy required to
      reorganize internal hydroxyl groups upon binding of the ligand to ConA.

PMID- 21085739
TI  - Racemisation dynamics of torsion angle restricted biphenyl push-pull cyclophanes.
AB  - The thermodynamics of the atropisomerisation of torsion angle restricted, axial
      chiral biphenyl-based push-pull cyclophanes were studied. Using (1)H NMR
      coalescence measurements the rotation barrier around the central C-C bond was
      determined to be 50 kJ mol(-1) for the propyl-bridged biphenyl derivative 1b,
      displaying only a negligible solvent dependence. By protonation of the
      piperidinyl nitrogen as electron donor, the free energy DeltaG(?)(T) of the
      rotation barrier increased, indicating that the tendency of the push-pull system
      to planarise may be considered as a driving force for the atropisomerisation. For
      the more restricted butyl-bridged cyclophane 1c a rotation barrier of
      DeltaG(?)(T) = 90 kJ mol(-1) was measured using dynamic chromatography. The
      difference in the free energy of rotation around the central C-C bond probably
      reflects the crowdedness of the transition states.

PMID- 21085740
TI  - Chemical genetics and cereal starch metabolism: structural basis of the non
      covalent and covalent inhibition of barley beta-amylase.
AB  - There are major issues regarding the proposed pathway for starch degradation in
      germinating cereal grain. Given the commercial importance but genetic
      intractability of the problem, we have embarked on a program of chemical genetics
      studies to identify and dissect the pathway and regulation of starch degradation
      in germinating barley grains. As a precursor to in vivo studies, here we report
      systematic analysis of the reversible and irreversible inhibition of the major
      beta-amylase of the grain endosperm (BMY1). The molecular basis of inhibitor
      action was defined through high resolution X-ray crystallography studies of
      unliganded barley beta-amylase, as well as its complexes with glycone site binder
      disaccharide iminosugar G1M, irreversible inhibitors alpha-epoxypropyl and alpha
      epoxybutyl glucosides, which target the enzyme's catalytic residues, and the
      aglycone site binders acarbose and alpha-cyclodextrin.

PMID- 21085741
TI  - Catalytic performance of plate-type Cu/Fe nanocomposites on ZnO nanorods for
      oxidative steam reforming of methanol.
AB  - The unique nanoarchitecture developed in this study and the use of replaceable
      stainless steel grids as catalyst supports certainly provide a promising platform
      technique for catalytic generation of high methanol conversion, hydrogen
      production rate and durability to produce electrical energy.

PMID- 21085742
TI  - International efforts in nanoinformatics research applied to nanomedicine.
AB  - BACKGROUND: Nanomedicine and nanoinformatics are novel disciplines facing
      substantial challenges. Since nanomedicine involves complex and massive data
      analysis and management, a new discipline named nanoinformatics is now emerging
      to provide the vision and the informatics methods and tools needed for such
      purposes. Methods from biomedi-cal informatics may prove applicable with some
      adaptation despite nanomedicine involving different biophysical and biochemical
      characteristics of nanomaterials and corresponding differences in information
      complexity. OBJECTIVES: We analyze recent initiatives and opportunities for
      research in nanomedicine and nanoinformatics as well as the previous experience
      of the authors, particularly in the context of a European project named ACTION
      Grid. In this project the authors aimed to create a collaborative environment in
      biomedical and nanomedical research among countries in Europe, Western Balkans,
      Latin America, North Africa and the USA. METHODS: We review and analyze the
      rationale and scientific issues behind the new fields of nanomedicine and
      nanoinformatics. Such a review is linked to actual research projects and
      achievements of the authors within their groups. RESULTS: The work of the authors
      at the intersection between these two areas is presented. We also analyze several
      research initiatives that have recently emerged in the EU and USA context and
      highlight some ideas for future action at the international level. CONCLUSIONS:
      Nanoinformatics aims to build new bridges between medicine, nanotechnology and
      informatics, allowing the application of computational methods in the nano
      related areas. Opportunities for world-wide collaboration are already emerging
      and will be influential in advancing the field.

PMID- 21085743
TI  - The nested structure of cancer symptoms. Implications for analyzing co-occurrence
      and managing symptoms.
AB  - OBJECTIVE: Although many cancer patients experience multiple concurrent symptoms,
      most studies have either focused on the analysis of single symptoms, or have used
      methods such as factor analysis that make a priori assumptions about how the data
      is structured. This article addresses both limitations by first visually
      exploring the data to identify patterns in the co-occurrence of multiple
      symptoms, and then using those insights to select and develop quantitative
      measures to analyze and validate the results. METHODS: We used networks to
      visualize how 665 cancer patients reported 18 symptoms, and then quantitatively
      analyzed the observed patterns using degree of symptom overlap between patients,
      degree of symptom clustering using network modularity, clustering of symptoms
      based on agglomerative hierarchical clustering, and degree of nestedness of the
      symptoms based on the most frequently co-occurring symptoms for different sizes
      of symptom sets. These results were validated by assessing the statistical
      significance of the quantitative measures through comparison with random networks
      of the same size and distribution. RESULTS: The cancer symptoms tended to co
      occur in a nested structure, where there was a small set of symptoms that co
      occurred in many patients, and progressively larger sets of symptoms that co
      occurred among a few patients. CONCLUSIONS: These results suggest that cancer
      symptoms co-occur in a nested pattern as opposed to distinct clusters, thereby
      demonstrating the value of exploratory network analyses to reveal complex
      relationships between patients and symptoms. The research also extends methods
      for exploring symptom co-occurrence, including methods for quantifying the degree
      of symptom overlap and for examining nested co-occurrence in co-occurrence data.
      Finally, the analysis also suggested implications for the design of systems that
      assist in symptom assessment and management. The main limitation of the study was
      that only one dataset was considered, and future studies should attempt to
      replicate the results in new data.

PMID- 21085744
TI  - From clinical practice guidelines to computer-interpretable guidelines. A
      literature overview.
AB  - BACKGROUND: Guidelines are among us for over 30 years. Initially they were used
      as algorithmic protocols by nurses and other ancillary personnel. Many physicians
      regarded the use of guidelines as cookbook medicine. However, quality and patient
      safety issues have changed the attitude towards guidelines. Implementing
      formalized guidelines in a decision support system with an interface to an
      electronic patient record (EPR) makes the application of guidelines more personal
      and therefore acceptable at the moment of care. OBJECTIVE: To obtain, via a
      literature review, an insight into factors that influence the design and
      implementation of guidelines. METHODS: An extensive search of the scientific
      literature in PubMed was carried out with a focus on guideline characteristics,
      guideline development and implementation, and guideline dissemination. RESULTS:
      We present studies that enable us to explain the characteristics of high-quality
      guidelines, and new advanced methods for guideline formalization,
      computerization, and implementation. We show how the guidelines affect processes
      of care and the patient outcome. We discuss the reasons of low guideline
      adherence as presented in the literature and comment upon them. CONCLUSIONS:
      Developing high-quality guidelines requires a skilled team of people and
      sufficient budget. The guidelines should give personalized advice. Computer
      interpretable guidelines (CIGs) that have access to the patient's EPR are able to
      give personal advice. Because of the costs, sharing of CIGs is a critical
      requirement for guideline development, dissemination, and implementation. Until
      now this is hardly possible, because of the many models in use. However, some
      solutions have been proposed. For instance, a standardized terminology should be
      imposed so that the terms in guidelines can be matched with terms in an EPR.
      Also, a dissemination model for easy updating of guidelines should be
      established. The recommendations should be based on evidence instead of on
      consensus. To test the quality of the guideline, appraisal instruments should be
      used to assess the guideline as a whole, as well as checking the quality of the
      recommendations individually. Only in this way optimal guideline advice can be
      given on an individual basis at a reasonable cost.

PMID- 21085746
TI  - Relationship between iron deficiency and anemia in children younger than 4 years.
AB  - OBJECTIVE: To evaluate the prevalence of anemia, iron deficiency and iron
      deficiency anemia in a cohort of children. METHODS: A cohort study nested in a
      randomized field trial. Children were recruited at birth at the maternity unit of
      the only public hospital in the city of Sao Leopoldo, southern Brazil. This study
      assessed iron status (hemoglobin and serum ferritin) when children were 12-16
      months old and later at the age of 3-4 years. Anemia was defined as hemoglobin
      concentration < 11.0 g/dL; iron deficiency as serum ferritin < 15.0 ug/L; and
      iron deficiency anemia as hemoglobin concentration < 11.0 g/dL with iron
      deficiency. RESULTS: At age 12-16 months, the overall prevalence of anemia, iron
      deficiency and iron deficiency anemia was 63.7, 90.3 and 58.8%, respectively. The
      values for age group 3-4 years were 38.1, 16.1 and 7.4%, respectively. At age 12
      16 months, 95% of anemia cases were associated with iron deficiency against only
      19.3% of cases at age 3-4 years. CONCLUSIONS: Iron deficiency was the main cause
      of anemia in the second year of life, but not at age 3-4 years. Thus, we point
      out that anemia in preschool children may have other causes and deserves careful
      assessment.

PMID- 21085745
TI  - A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of
      immature myeloid cells whose numbers dramatically increase in chronic and acute
      inflammatory diseases, including cancer, autoimmune disease, trauma, burns and
      sepsis. Studied originally in cancer, these cells are potently immunosuppressive,
      particularly in their ability to suppress antigen-specific CD8(+) and CD4(+) T
      cell activation through multiple mechanisms, including depletion of extracellular
      arginine, nitrosylation of regulatory proteins, and secretion of interleukin 10,
      prostaglandins and other immunosuppressive mediators. However, additional
      properties of these cells, including increased reactive oxygen species and
      inflammatory cytokine production, as well as their universal expansion in nearly
      all inflammatory conditions, suggest that MDSCs may be more of a normal component
      of the inflammatory response ("emergency myelopoiesis") than simply a
      pathological response to a growing tumor. Recent evocative data even suggest that
      the expansion of MDSCs in acute inflammatory processes, such as burns and sepsis,
      plays a beneficial role in the host by increasing immune surveillance and innate
      immune responses. Although clinical efforts are currently underway to suppress
      MDSC numbers and function in cancer to improve antineoplastic responses, such
      approaches may not be desirable or beneficial in other clinical conditions in
      which immune surveillance and antimicrobial activities are required.

PMID- 21085747
TI  - Early-onset neonatal sepsis: cord blood cytokine levels at diagnosis and during
      treatment.
AB  - OBJECTIVE: To assess clinical and laboratory parameters and serum cytokine levels
      in 55 neonates who developed early-onset sepsis. METHODS: Clinical parameters
      associated with early-onset neonatal sepsis were assessed. White blood cell
      differential and serum C-reactive protein and glucose levels were measured upon
      diagnosis of sepsis and 48 hours later. IL-beta, IL-10, IL-6, and TNF-alpha
      levels were measured in cord blood samples obtained on the day of diagnosis and
      from samples collected 48 and 96 hours after treatment onset. RESULTS: Among
      newborns with early-onset sepsis, the length of hospital stay was inversely
      correlated with birth weight. Clinical parameters varied widely, especially body
      temperature. Blood glucose changes - particularly hypoglycemia - were common.
      Leukopenia, usually due to neutropenia, was the most prevalent change in blood
      cell count. C-reactive protein levels correlated with the immature-to-total
      neutrophil ratio. Serum TNF-alpha and IL-10 levels measured early in the course
      of sepsis were positively correlated with those detected in cord blood.
      CONCLUSIONS: Clinical and laboratory parameters varied widely among neonates with
      sepsis in this sample. In neonates who presented with increased cytokine levels
      at birth, this abnormality persisted throughout the infectious process.

PMID- 21085748
TI  - [Changes in QUALIS! criteria].

PMID- 21085749
TI  - [Titrated oral solution of misoprostol for labour induction: a pilot study].
AB  - PURPOSE: To test effectiveness and safety of the oral administration of a new
      misoprostol formulation in titrated doses for the induction of delivery of a live
      fetus at term. METHODS: An open pilot multicenter, non-randomized clinical trial
      was conducted from July to December 2008. A total of 30 patients with indications
      for induction of labor were included. The patients had a live fetus, Bishop score
      <6, vertex presentation, fetal weight <4,000g estimated by ultrasonography and
      amniotic fluid index >5. Exclusion criteria were previous uterine scar, non
      reassuring fetal heart rate tracing, multiple pregnancy, fetal growth
      restriction, genital hemorrhage and presence of genital tumors, ulcerations or
      malformations. An initial dose of 20 ug/hour of the oral misoprostol solution was
      used in the first 6 hours, and was increased progressively to 20 ug/hour every 6
      hours if labor did not start, up to a maximum dose of 80 ug/h in the first 24
      hours, maintained for additional 24 hours if necessary. RESULTS: Labor was
      satisfactorily induced in 96.7% of patients. The interval between the first dose
      and the beginning of uterine contractions was 3.8 +/- 1.8 hours. The interval
      between the initial dose and delivery varied from 6 to 24 hours. The frequency of
      vaginal delivery was 80% (24 cases). Most of the patients (60%; n=18) initiated
      labor with a dose of 20 mg/hour. Tachysystole occurred in 13.3% of women and
      meconium-stained fluid was detected in 20% of cases. There were two cases of
      Apgar scores < 7 in the first minute and no Apgar score < 7 in the fifth minute.
      CONCLUSIONS: The oral solution of misoprostol was effective and safe for the
      induction of labor. However, further randomized controlled trials are needed to
      compare this new formulation with misoprostol administered by the vaginal route.

PMID- 21085750
TI  - [Laser ablation of placental vessels for treatment of severe twin-twin
      transfusion syndrome--experience from an university center in Brazil].
AB  - PURPOSE: To describe the results of laser ablation of placental vessels for the
      treatment of severe twin-to-twin transfusion syndrome in an university center in
      Brazil. METHODS: Retrospective observational study of patients treated at UNICAMP
      from 2007 to 2009. Laser ablation of placental vessels was performed in cases of
      severe twin-twin transfusion syndrome (Quintero stages II, III and IV) diagnosed
      before 26 complete weeks of gestation. The main variables evaluated in this
      series were gestational age at delivery, survival (discharge from the nursery) of
      at least one twin and neurological damage in survivors. Logistic regression was
      used to investigate the influence of cervical length, gestational age and stage
      of the disease (before the surgery) on the occurrence of delivery/abortion and
      fetal death after the intervention, and the influence on severe preterm birth and
      survival. RESULTS: In the whole series, at least one twin survived in 63.3% of
      cases (19/30). Among patients who did not have delivery/abortion after surgery,
      the survival of at least one twin was 82.6% (19/23). In this subgroup (n=23),
      mean gestational age in delivery was 31.9 weeks and neurological damage was
      identified in one neonate (1/31; 3.2%). Cervix length influenced the occurrence
      of delivery/abortion after surgery (p-value=0.008). Among seven patients (7/30;
      23.3%) who carried this complication, five (5/7; 71.4%) had cervix length lower
      than 15 mm. Among the 23 patients who did not have delivery/abortion as a result
      of the surgery, the highest stages of the disease (III and IV) increased the risk
      of delivery prior to 32 complete weeks of gestation (p-value=0.025) and decreased
      the chance of survival of both twins (p-value=0.026). CONCLUSIONS: The results
      are similar to those available in the literature. In our series, the main factors
      associated with poorer results were short cervix (lower than 15 mm) and the
      highest stages of the disease (III and IV) at the time of the treatment.

PMID- 21085751
TI  - [Comparison between two gestational diabetes screening tests and the perinatal
      outcome].
AB  - PURPOSE: To compare two screening tests for diabetes and their results to
      pregnancy outcomes. METHODS: In total, 279 pregnant women were submitted to two
      screening tests for gestational diabetes--fasting glycemia plus risk factors (FG
      + RF) and to the simplified glucose tolerance test (GTT50g). Screening by FG + RF
      consisted of the determination of fasting glycemia and anamnesis for the
      identification of risk factors on the occasion of the first prenatal visit. The
      GTT50g was performed between the 24th and the 28th week of pregnancy and
      consisted of the determination of plasma glycemia under fasting conditions and
      one hour after an oral overload with 50 g glucose. Positive and negative results
      were compared to pregnancy outcome. The dependent variables were: type of
      delivery, gestational age, weight and ponderal index at birth, Apgar indexes <7
      in the 1st and 5th minutes, need for admission to the Intensive Care Unit (ICU),
      duration of hospitalization, and neonatal death. Data were analyzed statistically
      through the Students t-test, and the level of significance was set at 5%.
      RESULTS: Only two of the perinatal variables studied were distinguished by the
      tests. An abnormal GTT50g was associated with a greater proportion of cesarean
      deliveries (58.7 versus 34.3%) and a positive FG + RF association was related to
      a higher rate of premature births (15.4 versus 5.4%). The other dependent
      variables did not differ among patients with positive and negative results of the
      two screening tests. CONCLUSIONS: Despite the relation between prematurity and a
      positive FG + RF association, the increase of caesarean sections and the abnormal
      GTT50g, it would be a critical failure to accept these associations as
      definitive. Among others explanations, multiple intercurrent factors and the
      characteristics of the screening tests themselves should be considered.

PMID- 21085752
TI  - [Progesterone receptor gene polymorphism and recurrent spontaneous abortion].
AB  - PURPOSE: To assess a possible association between polymorphism of the
      progesterone receptor gene (PROGINS) and recurrent spontaneous abortion (RSA).
      METHODS: In this case-control study, 85 women with at least three previous
      spontaneous abortions without an identifiable cause (RSA Group) and 157 women
      with at least two previous term pregnancies without pathologies and no previous
      miscarriage (Control Group) were selected. An amount of 10 mL of peripheral blood
      was collected by venipuncture and genomic DNA was extracted by the DTAB/CTAB
      method, followed by the polymerase chain reaction (PCR) under specific conditions
      for this polymorphism and by amplification by 2% agarose gel electrophoresis. The
      bands were visualized with an ultraviolet light transilluminator and the gels
      were photographed. Differences in the PROGINS genotype and allele frequencies
      between groups were analyzed by the chi2 test, with the level of significance set
      at p<0.05. The Odds Ratio (OR) was also used, with 95% confidence intervals
      95%CI. RESULTS: PROGINS genotypic frequencies were 72.3% T1T1 and 27.7% T1T2 for
      the RSA group and 76.4% T1T1, 22.3% T1T2 and 1.3% T2T2 for the control group.
      There were no differences between groups when the genotype and allele frequencies
      were analyzed: respectively p=0.48 (OR: 0.8) and p=0.65 (OR: 0.9). CONCLUSIONS:
      Our results suggest that PROGINS polymorphism is not associated with RSA.

PMID- 21085753
TI  - [Pelvic floor muscle training in female sexual dysfunctions].
AB  - PURPOSE: To evaluate the effect of pelvic floor muscle training (PFMT) on female
      sexual dysfunctions. METHODS: Twenty-six women with a diagnosis of sexual
      dysfunction (sexual desire, arousal, orgasmic disorders and/or dyspareunia) were
      included in a clinical trial with a before/after approach . The assessment was
      carried out before, during (after five sessions) and at the end of the treatment
      (after ten sessions) by two-digit palpation (assessment of pelvic floor muscle,
      PFM, strength), intravaginal electromyography (EMG) (capture of PFM contraction
      amplitudes) and Female Sexual Function Index (FSFI, a questionnaire for the
      evaluation of sexual function). The women underwent PFMT in different positions
      for ten sessions (once or twice a week). For statistical analysis, absolute and
      relative frequencies were used for clinical characteristics and PFM strength. The
      Friedman test was used to compare the FSFI domain scores and EMG values, the
      Students t-test was used to determine the association between these values and
      the characteristics of the women, and the Wilcoxon test for percent modification
      of the EMG. The Mann-Whitney test permitted us to compare these values with
      clinical characteristics. The Spearman correlation test was used to correlate the
      EMG values with mean total score. Results were considered statistically
      significant if p<0.05. RESULTS: A significant improvement (p<0.0001) of FSFI
      scores was observed at the end of treatment compared to the values observed
      before and in the middle of treatment. Regarding the EMG, the amplitudes of tonic
      and phasic contractions increased significantly during treatment (p<0.0001).
      Pelvic floor strength increased, which 69% of the women presenting grade 4 or 5
      at the end of treatment, with a total improvement of sexual complaints.
      CONCLUSIONS: The PFMT improved muscle strength and electromyography contraction
      amplitudes, with improved sexual function, indicating that this physiotherapy
      approach may be successfully used for the treatment of female sexual
      dysfunctions.

PMID- 21085754
TI  - [Knowledge, practice and attitude about breast self-exam from women of a
      Northeastern municipality, Brazil].
AB  - PURPOSE: To assess the knowledge, attitude and practice of breast self
      examination (BSE) of women from the municipality of Sao Luis (MA), Brazil, and
      associated socio-demographic variables. METHODS: Prospective and cross-sectional
      study, with conglomerate sampling, in which 552 women from 14 census sections of
      Sao Luis were included during the period from January to September 2003. The
      knowledge, attitude and practice (dependent variables) were evaluated by means of
      analysis of the responses of the women as "adequate" or "inadequate". The main
      independent variables were: age, schooling, family income and marital and
      menopausal status. The chi2 test was used to determine the association between
      categorical variables and the measurement of the crude/adjusted Odds Ratio (OR)
      after multivariate analysis by means of logistic regression. RESULTS: Although
      1/3 of the studied population did not know about BSE, the group of women who were
      informed about it showed adequate knowledge (60.9%), practice (59.5%) and
      attitude (90%). The family history of breast cancer (8.9%) was not associated
      with better knowledge and practice. The media (63.6%) was found to be important
      in disseminating information about BSE. After multivariate analysis, women with a
      partner (OR=1.9) presented more adequate knowledge; women older than 50 years
      (OR=11.7) had a better attitude towards BSE; women with more than five years of
      schooling (OR=2) and with a partner (OR=1.7) were associated with a more correct
      practice of BSE. CONCLUSION: Most of the patients know and practice the BSE in
      Sao Luis and their attitude towards the procedure is extremely positive. There
      was a great participation of the media in the dissemination of information
      concerning BSE.

PMID- 21085755
TI  - [Quality of life of women with chronic pelvic pain: a cross-sectional analytical
      study].
AB  - PURPOSE: To compare the quality of life (QL) of women with and without chronic
      pelvic pain (CPP) and to investigate the factors associated with QL in women with
      CPP. METHODS: A cross-sectional study was conducted on 30 women with CPP and 20
      women without CPP. Sociodemographic and clinical characteristics were evaluated.
      QL was investigated by applying the SF-36 questionnaire, which contains eight
      domains: functional capacity, physical aspects, pain, general health status,
      vitality, social aspects, emotional aspects, and mental health. These domains can
      be summarized into two groups: physical component summary (PCS) and mental
      component summary (MCS). Pain intensity was investigated by applying the visual
      analogue scale. Linear regression analysis was used to compare QL scores between
      women with and without CPP and to identify factors associated with the QL of
      women with CPP. RESULTS: The mean age of women with and without CPP was 35.2 +/-
      7.5 and 36 +/- 9.3 years (p=0.77), respectively. Women with CPP had a lower
      monthly family income (p=0.04) and a higher prevalence of dysmenorrhea (87 versus
      40%; p<0.01) and depression (30 versus 5%; p=0.04) compared to women without CPP.
      Adjusted analysis for potential confounding variables revealed that women with
      CPP had lower QL scores in the pain (p<0.01) and social aspects (p<0.01) domains.
      Depression was negatively associated with the emotional aspects domain (p=0.05)
      and with the MCS (p=0.03), while pain intensity was negatively related to the
      pain domain (p<0.01) of the QL of women with CPP. CONCLUSIONS: Women with CPP
      presented a worse QL compared to women without CPP. Depression and pain intensity
      were negatively related to the QL of women with CPP. Thus, the evaluation and
      treatment of pain and depressive symptoms must be among the priorities that aim
      to improve the QL of women with CPP.

PMID- 21085756
TI  - [VI Brazilian Guidelines on Hypertension].

PMID- 21085757
TI  - [II Guidelines of Brazilian Society of Cardiology in geriatric cardiology].

PMID- 21085758
TI  - Endoscopic left sympathetic blockade in the treatment for dilated cardiomyopathy.
AB  - BACKGROUND: The level of sympathetic nervous activity is a major determinant of
      prognosis in patients with heart failure. OBJECTIVE: The purpose of this
      investigation was to perform a proof-of-principle trial of therapeutic endoscopic
      left thoracic sympathetic blockade in heart failure patients to assess safety and
      immediate effects. METHODS: Fifteen patients with dilated cardiomyopathy and left
      ventricular ejection fraction (LVEF) < 40%, New York Heart Association functional
      class II or III, and heart rate > 65 bpm, despite either adequate betablocker use
      or intolerant to it, were enrolled. Ten patients underwent left infra-stellate
      ganglion plus T3-T4 interspinal space clipping through videothoracoscopy, while
      the other five patients were randomized to a control group. RESULTS: None of the
      treated patients had any procedure-related adverse cardiovascular events at the
      perioperative period. Two patients from the surgical group died due to pulmonary
      thromboembolism or myocardial infarction within 6 months of the initial follow
      up, while three patients from the control group had heart failure progression and
      died or developed cardiogenic shock during the same period. Treated patients
      presented improvement in quality of life, level of physical activity and LVEF
      (from 25 +/- 9% to 32 +/- 8%, p=0.024) at 6 months of follow-up, whereas these
      parameters did not change in control patients. CONCLUSION: Endoscopic left
      thoracic sympathetic blockade is feasible and appears to be safe in severe heart
      failure patients. This initial study suggests that this procedure might be an
      effective alternative approach to sympathetic blockade in the treatment of
      dilated cardiomyopathies.

PMID- 21085760
TI  - Anthropometric indicators as predictors of high blood pressure in adolescents.
AB  - BACKGROUND: Hypertension is related to increased body fat, which can be evaluated
      by anthropometric indicators. OBJECTIVE: To determine the predictive power of
      anthropometric indicators and establish their cutoff points as discriminators of
      high blood pressure. METHODS: Cross-sectional study with a sample of 660
      adolescents aged 14 to 19 including 51.9% girls. We considered the following
      anthropometric indicators: body mass index (BMI), waist circumference, waist-to
      height ratio and conicity index. High blood pressure was characterized by values
      above the 90th percentile for systolic and/or diastolic blood pressure. To
      identify predictors of high blood pressure, we adopted the analysis of receiver
      operating characteristic curves (ROC) with a confidence interval of 95%.
      Subsequently, we identified the cutoff points with their relevant sensitivities
      and specificities. RESULTS: The areas under the ROC curves with confidence
      intervals were: boys--waist circumference = 0.80 (0.72 to 0.89); BMI = 0.79 (0.68
      to 0.89), waist-to-height ratio = 0.77 (0.66 to 0.88); conicity index = 0.69
      (0.56 to 0.81) and for girls--waist circumference = 0.96 (0.92 to 1.00); BMI 0.95
      (0.87 to 1.00), waist-to-height ratio = 0.93 (0.85 to 1.00); conicity index =
      0.74 (0.50 to 0.98). The different cutoff points of anthropometric indicators
      with better predictive power and their relevant sensitivities and specificities
      were identified. CONCLUSION: Although the waist-to-height ratio and BMI have
      shown good areas under the ROC curve, we suggest the use of waist circumference
      to predict high blood pressure.

PMID- 21085761
TI  - Body mass index and hypertension in adult subjects in Brazil's Midwest.
AB  - BACKGROUND: Overweight and obesity are an important public health problem in
      society, due to the growth in all age groups and their association with various
      chronic diseases, especially hypertension OBJECTIVE: To investigate possible
      factors associated with changes in body mass index (BMI). METHODS: Study
      developed in the city of Nova Andradina, State of Mato Grosso do Sul, with 369
      subjects registered in the Family Health Strategy Program in 2007. Data were
      collected at the subjects' homes, by using a semi-structured interview and by an
      anthropometric assessment. In the analysis of data, we used the Chi-square and
      Mantel Haenszel tests, for categorical responses, and ANOVA and Tukey tests, for
      continuous responses. RESULTS: The prevalence of overweight and obesity was 33.3%
      and 23.0%, respectively. Most of the individuals had the following
      characteristics: they were female (85.4%), physically inactive (89.7%), their
      waist-hip ratio (WHR) was inadequate (83.7%) and they had some chronic health
      problem (31.9%), especially hypertension. Risk factors for overweight and obesity
      may be linked to variables such as widowed status, inadequate WHR, lower income
      and health problems. On the other hand, high blood pressure may be linked only to
      obesity. CONCLUSION: The percentage of people that were overweight and those who
      did not do exercises in Nova Andradina indicates that these issues are also an
      important challenge for the health sector in smaller cities. Therefore, it is
      urgent that multidisciplinary intervention programs be implemented in primary
      health care.

PMID- 21085762
TI  - Defining reference values for TSH: nearing perfection in a imperfect world.

PMID- 21085763
TI  - The PI3K signaling pathway mediates the biological effects of leptin.
AB  - The activation of the leptin receptor recruits several intracellular signaling
      pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway. While some
      of the leptin-induced signaling pathways, such as the JAK2/STAT3 pathway, induce
      cellular responses primarily through changes in gene expression, the PI3K pathway
      affects cellular properties more rapidly, through post-translational changes such
      as protein phosphorylation. Accordingly, several studies have shown that the PI3K
      pathway is required for the acute effects of leptin, such as a leptin-induced
      decrease in food intake. Leptin signaling through PI3K also affects the
      electrophysiological properties of neurons, including changes in their membrane
      potential and firing rates. In this review, we summarize the recent advances in
      our understanding of the role played by the PI3K signaling pathway in controlling
      food intake and energy balance. In particular, we focus on the importance of the
      PI3K signaling pathway as a mediator of the effects of leptin on hypothalamic
      neurons.

PMID- 21085764
TI  - TSH reference values for adult Brazilian population.
AB  - OBJECTIVE: To establish limits of normal serum TSH for the adult (18 to 60 years)
      Brazilian population according to recommendations of the National Academy of
      Clinical Biochemistry. SUBJECTS AND METHODS: Healthy volunteers were evaluated
      and those fulfilling the following clinical criteria were selected: absence of
      known thyroid disease; no use of any interfering medications; no history of head
      and neck external radiotherapy, type 1 diabetes or autoimmune disease; no family
      history of thyroid disease, and absence of goiter or palpable nodules. Subjects
      with anti-thyroperoxidase antibodies and/or altered free T4 were excluded. The
      sample consisted of 960 subjects (480 males and 480 females). RESULTS: TSH values
      corresponding to the 2.5th and 97.5th percentiles of the sample were 0.43 and
      3.24 mIU/L, respectively. TSH values > 2.5 mIU/L were observed in 9.15% of the
      volunteers and levels > 3 mIU/L in 3.11%. CONCLUSION: The present study suggests
      an upper limit of normal TSH of approximately 3.5 mIU/L.

PMID- 21085765
TI  - Prevalence of central obesity in a large sample of adolescents from public
      schools in Recife, Brazil.
AB  - OBJECTIVE: To determine the prevalence and association of central obesity (CO)
      and hypertension and its associations with alcohol intake, smoking and physical
      activity in adolescents. SUBJECTS AND METHODS: Cross sectional study in 1,824
      students from 29 public schools in Recife. RESULTS: 89.6% were normal weight,
      6.7% overweight and 3.7% obese; 77.2% were normotensive, 5.9% prehypertensive and
      16.9% hypertensive; CO was 10.2% when the 90th percentile was used as cutoff and
      25.2% when the 75th percentile was used. There was a higher likelihood of central
      obesity among students aged 18 to 20 years, smoking and alcohol intake. The
      probability of hypertension increases if the subject is male, has a waist
      circumference (WC) >= 90, WC >= 75 and does not practice physical activity.
      CONCLUSIONS: A high prevalence of CO and hypertension was found in adolescents.
      CO was more frequent in students aged 18 to 20 years, smokers and with alcohol
      intake and hypertension was associated with male, CO and no physical activity.

PMID- 21085766
TI  - Impact of previous insulin therapy on the prognosis of diabetic patients with
      acute coronary syndromes.
AB  - OBJECTIVE: To determine whether previous insulin treatment independently
      influences subsequent outcomes in diabetic patients with ACS (acute coronary
      syndromes). SUBJECTS AND METHODS: 375 diabetic patients with ACS, divided in 2
      groups: Group A (n = 69)--previous insulin and Group B (n = 306)--without
      previous insulin. Predictors of 1-year mortality and major adverse cardiac events
      (MACE) were analyzed by Cox regression analysis. RESULTS: Group A had more
      previous stroke (17.4% vs. 9.2%, p = 0.047) and peripheral artery disease (13.0%
      vs. 3.6%, p = 0.005). They had significantly higher admission glycemia and lower
      LDL cholesterol. There were no significant differences in the type of ACS, in 1
      year mortality (18.2% vs. 10.4%, p = 0.103) or MACE (32.1% vs. 23.0%, p = 0.146)
      between groups. In multivariate analysis, insulin treatment was neither an
      independent predictor of 1-year mortality nor of MACE. CONCLUSION: Despite the
      more advanced atherosclerotic disease, diabetics under insulin had similar
      outcomes to those without insulin. Insulin may protect diabetics from the
      expected poor adverse outcome of an advanced atherosclerotic disease.

PMID- 21085767
TI  - [Retrospective study of the maternal, fetal and perinatal outcomes in diabetic
      women in twenty years of assistance in the Universidade Federal do Triangulo
      Mineiro School Hospital].
AB  - OBJECTIVES: Evaluation of the consequences of diabetes mellitus (DM) on maternal
      and fetal morbidity and mortality at Universidade Federal do Triangulo Mineiro.
      MATERIALS AND METHODS: A retrospective review of medical records of pregnant
      women with diabetes was carried out at the hospital between 1990-2009, focusing
      on maternal and neonatal data and complications. RESULTS: The last pregnancy of
      93 diabetics was evaluated. In thirty-four patients with type 1 diabetes a higher
      incidence of birth trauma (p = 0.023) and retinopathy (p = 0.023) was observed.
      Twenty-one type 2 DM subjects required progressively increased insulin therapy (p
      < 0.01) and showed a higher prevalence of smoking (p = 0.004). Thirty-eight had
      gestational diabetes. Their diabetic follow-up started at a later gestational age
      (p < 0.001), had more fetal macrosomia histories (p = 0.028) and cardiovascular
      risk factors. CONCLUSIONS: Despite improvement of glycemic control during
      pregnancy neither group attained the glycemic target. However, the majority of DM
      pregnancies evaluated in our group presented successful outcomes.

PMID- 21085768
TI  - [Evaluation of cardiovascular risk by the LAP index in non-obese patients with
      polycystic ovary syndrome].
AB  - OBJECTIVE: To analyze the cardiovascular risk of non-obese women with polycystic
      ovary syndrome (PCOS) by the LAP index (lipid accumulation product). SUBJECTS AND
      METHODS: 283 patients (18-34 years) assigned at the University Hospital of the
      Federal University of Rio Grande do Norte, Natal-RN, were divided into four
      groups: 1) lean PCOS (n = 35); 2) healthy lean (n = 162); 3) overweight PCOS (n =
      28); 4) healthy overweight (n = 58). RESULTS: Patients with PCOS showed higher
      values of the LAP index than healthy controls: lean (22.26 vs. 15.87 cm.mmol/L; p
      = 0.007); overweight (40.83 vs. 26.32 cm.mmol/L; p = 0.001). The percentage of
      women above the 75th percentile of the LAP index was also higher in the subgroups
      with PCOS: lean (17.1 vs. 6.8%; p = 0.04); overweight (37.5 vs. 13.8%; p = 0.01).
      CONCLUSIONS: In our sample, patients with PCOS showed higher cardiovascular risk
      assessed by the LAP index in relation to healthy women, even in the absence of
      obesity.

PMID- 21085769
TI  - [Analysis of several anthropometric measurements for the identification of
      metabolic syndrome, with or without disturbance of glucose metabolism].
AB  - OBJECTIVE: This study compared anthropometric measurements and insulin resistance
      indexes of individuals with or without metabolic syndrome (MS), stratified by the
      presence of glycemic abnormalities. SUBJECTS AND METHODS: 454 individuals (66%
      women, 54% Caucasians) were included, being 155 allocated to group 1 (without MS,
      without glycemic abnormality), 32 to group 2 (without MS, with glycemic
      abnormality), 104 to group 3 (with MS, without glycemic abnormality), and 163 to
      group 4 (with MS, with glycemic abnormality). Groups were compared by ANOVA.
      RESULTS: Those with MS (3 and 4) showed the worst anthropometric and lipid
      profiles; in group 2, despite higher plasma glucose levels, the mean values of
      anthropometric variables and lipids did not differ from group 1. The highest mean
      values of HOMA-IR were found in the groups with MS, while group 2 showed the
      lowest HOMA-beta. Triglyceride was the metabolic variable with the highest
      correlation coefficients with anthropometry. However, the strongest correlations
      were those of waist circumference (r = 0.503) and waist-to-height ratio (r =
      0.513) with HOMA-IR (p < 0.01). CONCLUSION: Our findings indicate that, in a
      sample of the Brazilian population, any anthropometric measure identifies
      individuals with MS, but such measurements seem to be unable to differentiate
      those with glycemic disturbance. We reinforce the strongest relationship of
      measures of central adiposity with insulin resistance, suggesting utility for the
      waist-to-height. An autoimmune component may be contributing to the deterioration
      of glucose metabolism of individuals from group 2.

PMID- 21085770
TI  - [Questionnaire of Diabetes Self-Care Activities: translation, cross-cultural
      adaptation and evaluation of psychometric properties].
AB  - OBJECTIVES: To translate into Portuguese, perform cross-cultural adaptation and
      to evaluate the psychometric properties of the Summary of Diabetes Self-Care
      Activities Questionnaire - SDSCA. MATERIALS AND METHODS: The process followed the
      international guidelines for the adaptation and evaluation of psychometric
      properties. The Cronbach's alpha (alpha) was determined to evaluate the internal
      consistency (inter-itens correlation) and the reliability (test-retest and inter
      evaluator correlation). RESULTS: The inter-itens correlation showed values of
      alpha = 0.09 to alpha = 0.86. In the test-retest evaluation, the lowest
      correlation was obtained for the item "eat sweets" (alpha = 0.15) and the highest
      correlation was obtained for the items concerning smoking (alpha = 1.00). The
      inter-evaluator correlations varied from alpha = 0.29 to alpha = 1.00.
      CONCLUSIONS: The adapted questionnaire showed psychometric properties similar to
      those of the SDSCA. Its Brazilian version provides a reliable and valid
      questionnaire to evaluate diabetic patient adherence to self-care in our
      community.

PMID- 21085771
TI  - Correlation of shift work and waist circumference, body mass index, chronotype
      and depressive symptoms.
AB  - OBJECTIVE: Correlate shift work with body mass index (BMI), waist circumference,
      chronotype and depressive symptoms. SUBJECTS AND METHODS: This study comprising
      14 shift workers and 13 day workers. Subjects were workers from the health area
      aged 25 to 60 years. Minor psychiatric disorders were accessed by Self Report
      Questionnaire (SRQ-20) and depressive symptoms by Beck Depression Inventory
      (BDI). Chronotype was accessed using Morningness-Eveningness Questionnaire (MEQ).
      Anthropometric measures were taken. RESULTS: Shift workers presented higher BMI
      (P = 0.03) and waist circumference (P = 0.004) than day workers. Years on shift
      work were significantly correlated to waist circumference (r = 0.43; P = 0.03)
      and age (r = 0.47; P = 0.02). Shift work was not correlated with depressive
      symptoms and chronotype. CONCLUSION: These results may suggest a role played by
      shift work on the development and/or the early clinic manifestations of metabolic
      disturbances, becoming a risk factor to metabolic syndrome.

PMID- 21085772
TI  - Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case
      report and review.
AB  - Spindle epithelial tumor with thymus-like element (SETTLE) is a rare malignant
      neoplasm of the thyroid, occurring predominantly in children, adolescents, and
      young adults. SETTLE usually presents itself as a thyroid mass, without
      metastases at diagnosis. It is believed to derive from branchial pouch or thymic
      remnant tissue showing primitive thymic differentiation. This article reports the
      clinical, cytological, histological and immunohistochemical features of a SETTLE
      in a 3-year-old girl. Microscopic exam revealed a nodular, highly cellular
      neoplasm displayed in the classic biphasic pattern, with mixture of prominent
      spindle cell component and a minor glandular component lined by mucinous or
      respiratory-type epithelium. The immunohistochemical study showed strong and
      diffuse positivity for pan-CK, vimentin and smooth muscle actin. The present case
      is the first SETTLE case reported in Brazil. To date, the patient described
      remains without evidence of recurrence or metastasis 5 years after surgery.

PMID- 21085773
TI  - Severe HDL-c reduction during rosiglitazone therapy in an obese woman with type 2
      diabetes.
AB  - Treatment with rosiglitazone has been associated with severe paradoxical HDL-c
      reductions. To our knowledge, there are very few reports of this reaction
      occurring when patients are treated without the combination of a fibrate. A case
      of severe HDL-c lowering in a patient treated with rosiglitazone without a
      fibrate is presented. The patient has been treated at a private practice clinic
      in southern Brazil. A 64-year-old woman with a 2-year history of type 2 diabetes
      mellitus was referred to her endocrinologist in June 2008. Rosiglitazone 4 mg
      q.d. was prescribed. Nine months later, the patient experienced a 90.90% decrease
      of her HDL-c levels. Rosiglitazone was withdrawn and the HDL-c returned to
      baseline. This paradoxical HDL-c reduction is a potentially severe adverse event.
      Patients prescribed rosiglitazone should have their HDL-c levels measured before
      and during therapy.

PMID- 21085774
TI  - Measurement of basal GH in the diagnosis of acromegaly.

PMID- 21085775
TI  - Ecohydrology for compensation of Global Change.
AB  - Water in the XXI century has become the primary factor for sustainable
      development, eradication of poverty and reversal of ecosystem degradation.
      Increasing water demand for agriculture and urbanisation, combined with
      pollution, eutrophication and amplification of the stochastic character of
      climatic processes, increases water limitations for ecosystems and societies. The
      transdisciplinary science of Ecohydrology, which has been developed in the
      framework of the International Hydrological Programme of UNESCO, provides a
      systemic approach, to regulate hydrology-ecosystem-society interplay towards: 1)
      slowing down the transfer of water from the atmosphere to the sea, still
      considered as a priority to reduce the severity of floods and droughts impact; 2)
      reducing input and regulating the allocation of excess nutrients and pollutants
      to aquatic ecosystems, toward reversing ecosystems degradation and improvement of
      human well being; and 3) harmonisation of ecosystem potential with societal needs
      within the framework of IWRM.

PMID- 21085776
TI  - Brazilian Atlantic Forest lato sensu: the most ancient Brazilian forest, and a
      biodiversity hotspot, is highly threatened by climate change.
AB  - After 500 years of exploitation and destruction, the Brazilian Atlantic Forest
      has been reduced to less the 8% of its original cover, and climate change may
      pose a new threat to the remnants of this biodiversity hotspot. In this study we
      used modelling techniques to determine present and future geographical
      distribution of 38 species of trees that are typical of the Brazilian Atlantic
      Forest (Mata Atlantica), considering two global warming scenarios. The optimistic
      scenario, based in a 0.5% increase in the concentration of CO2 in the atmosphere,
      predicts an increase of up to 2  degrees C in the Earth's average temperature; in
      the pessimistic scenario, based on a 1% increase in the concentration of CO2 in
      the atmosphere, temperature increase may reach 4  degrees C. Using these
      parameters, the occurrence points of the studied species registered in
      literature, the Genetic Algorithm for Rule-set Predictions/GARP and Maximum
      entropy modeling of species geographic distributions/MaxEnt we developed models
      of present and future possible occurrence of each species, considering Earth's
      mean temperature by 2050 with the optimistic and the pessimistic scenarios of CO2
      emission. The results obtained show an alarming reduction in the area of possible
      occurrence of the species studied, as well as a shift towards southern areas of
      Brazil. Using GARP, on average, in the optimistic scenario this reduction is of
      25% while in the pessimistic scenario it reaches 50%, and the species that will
      suffer the worst reduction in their possible area of occurrence are: Euterpe
      edulis, Mollinedia schottiana, Virola bicuhyba, Inga sessilis and Vochysia
      magnifica. Using MaxEnt, on average, in the optimistic scenario the reduction
      will be of 20% while in the pessimistic scenario it reaches 30%, and the species
      that will suffer the worst reduction are: Hyeronima alchorneoides, Schefflera
      angustissima, Andira fraxinifolia and the species of Myrtaceae studied.

PMID- 21085778
TI  - Photosynthetic efficiency of Clusia arrudae leaf tissue with and without
      Cecidomyiidae galls.
AB  - Leaf galls induced by a still undescribed new species of Cecidomyiidae (Diptera)
      are frequent on leaves of Clusia arrudae Planchon & Tirana (Clusiaceae) in the
      rupestrian fields at 1400 m a.s.l. in Serra do Cipo, Minas Gerais, Brazil. Galls
      were 7.1 +/- 0.7 mm in diameter, one chambered with only one larva inside. Gall
      tissue is green and soft. Assessments of photosynthetic capacity using
      chlorophyll-a fluorescence measurements revealed that photosynthetic performance
      of gall tissue and healthy leaf tissue were rather similar. Hence, the
      morphological changes due to gall development were not associated with
      significant changes in the photosynthetic capacity of the tissue.

PMID- 21085777
TI  - Dissolved nitrogen in rivers: comparing pristine and impacted regions of Brazil.
AB  - Riverine nitrogen distribution is increasingly controlled by anthropogenic
      activities in their watersheds, regardless of spatial scale, climate, and
      geographical zone. Consequently, modelling efforts to predict the export of
      nitrogen from rivers worldwide have used attributes such as population density,
      land use, urbanization and sanitation. These models have greatly enhanced our
      understanding of the sources and fate of nitrogen added to terrestrial systems
      and transported to rivers and streams, especially for developed countries of the
      North temperate zone. However, much of the world's population lives in developing
      countries of the tropics, where the effects of human activities on riverine N
      exports are still poorly understood. In an effort to close this gap, we compare
      riverine nitrogen data from 32 Brazilian rivers draining two contrasting regions
      in this tropical country in terms of economic development - the State of Sao
      Paulo and the Amazon. Our data include nitrogen in different dissolved forms,
      such as Dissolved Inorganic Nitrogen (DIN) and Dissolved Organic Nitrogen (DON).
      The results show that nitrogen concentrations decreased as river runoff increased
      in both study areas, and that concentrations were significantly higher in rivers
      draining the most economically developed region. The relationships between
      nitrogen concentrations and fluxes with demographic parameters such as population
      density were also determined and compared to those in temperate systems. In
      contrast to temperate watersheds, we found that nitrogen fluxes increased only
      after population densities were higher than 10 individuals per km2.

PMID- 21085779
TI  - Spectral analysis of flowers used by nectar-feeding birds in an urban area in
      Southeastern Brazil.
AB  - The objective of this study was to determine the spectral characteristic of
      nectar-producing flowers visited by nectarivorous birds in urban areas. This
      study was carried out in the central area of the city of Taubate, in the
      northeast of the State of Sao Paulo. The sample areas included green areas, such
      as squares and parks, and the vegetation of streets and avenues. Twelve plant
      species were recorded with flowers visited by five nectar-feeding birds. The most
      visited flower species were those that reflected in long wavelengths (>600 nm).
      The study discussed the birds' detection capability due to the tetrachromatic
      vision of nectar-feeding birds and the conspicuity of flowers in urban
      environments. Finally, the study assessed the scarcity of plants attractive to
      nectar-feeding birds and the need for a management strategy to favour these
      species and biodiversity in urban areas.

PMID- 21085780
TI  - Abundance and stratification of soil macroarthropods in a Caatinga Forest in
      Northeast Brazil.
AB  - In arid and semiarid environments, seasonality usually exerts a strong influence
      on the composition and dynamics of the soil community. The soil macroarthropods
      were studied in a Caatinga forest located in the Reserva Particular do Patrimonio
      Natural (RPPN) Fazenda Almas, Sao Jose dos Cordeiros, Paraiba, Brazil. Samples
      were collected during the dry and rainy seasons following the method proposed by
      the Tropical Soil Biology and Fertility Program (TSBF), with minor modifications.
      At each station, 15 soil blocks (20 * 20 * 30 cm: 12 L) were extracted and
      divided into three layers: A (0-10 cm), B (10-20 cm), and C (20-30 cm). In the
      rainy and dry seasons 1,306 +/- 543(se) and 458 +/- 212 ind.m-2 macroarthropods
      were found, respectively, with 35 and 18 respective taxa recorded. The abundance
      of individuals and taxa were significantly higher in the rainy season. Isoptera
      (57.8%) was the most abundant taxon, followed by Hymenoptera: Formicidae (17.2%),
      Coleoptera larvae (7.3%), and Araneae (3.5%). In the rainy season, abundance in
      layer A (576 +/- 138 ind.m-2) was significantly higher than that of layer C (117
      +/- 64 ind.m-2), but was not different from layer B (613 +/- 480 ind.m-2). There
      was also no difference between the layer B and C abundances. In the dry season,
      abundance in layer B (232 +/- 120 ind.m-2) was not significantly different
      compared to layer A (182 +/- 129 ind.m-2), but was significantly higher than
      abundance in layer C (44 +/- 35 ind.m-2). During the rainy season, layer A (34
      taxa) was significantly richer in taxa than layers B (19 taxa) and C (11 taxa).
      On the other hand, during the dry season the richness of layers A (12 taxa) and B
      (12 taxa) was equal, but significantly higher than that of layer C (6 taxa).
      Richness of taxa and abundance were positively correlated with soil organic
      matter and negatively correlated with soil temperature. The community of soil
      macroarthropods in the area of Caatinga studied has taxonomic and functional
      structures that are relatively complex and is therefore likely to exert an
      influence on ecosystem productivity due to its physical effects on soil profile
      and necromass fragmentation, as occurs in other arid and semiarid ecosystems
      throughout the world.

PMID- 21085781
TI  - Nutrient addition does not enhance leaf decomposition in a Southeastern Brazilian
      stream (Espinhaco mountain range).
AB  - A decomposition experiment using eucalyptus leaves was carried out in a
      Southeastern Brazilian mountain stream located at the transition between the
      Cerrado and the Atlantic Forest to test whether nutrient addition increases
      microbial and invertebrate colonisation and accelerates breakdown rates. The
      results show that none of the tested variables was significantly affected by
      nutrient addition, despite the average increase in ATP concentrations and
      invertebrate colonisation observed in the fertilised leaf bags. This could mean
      that breakdown in the stream was already at its maximum due to the relatively
      high water temperature and nutrient content, or that the breakdown rate of
      eucalyptus leaves was too fast to allow the detection of any effects of nutrient
      addition. Breakdown rates of eucalyptus leaves were much faster than the values
      reported in literature for most species in Brazilian Cerrado streams, suggesting
      that the replacement of the natural vegetation by eucalyptus may affect nutrient
      dynamics in the region.

PMID- 21085782
TI  - Cladocera of the Lencois Maranhenses (NE - Brazil): faunal composition and a
      reappraisal of Sars' Method.
AB  - We studied the Cladocera of a group of ephemeral interdunal pools in the Lencois
      Maranhenses, Maranhao State (NE - Brazil) and recorded 34 species. The fauna was
      overwhelmingly neotropical, with no evidence of invasive species. Species
      composition differed in Lagoa da Colher, an acid system. We provide notes on
      behaviour, morphology and taxonomy of some lesser-known anomopods, with emphasis
      on the Chydoridae. We figure male Oxyurella longicaudis, Chydorus eurynotus,
      Disparalona leptorhyncha, Alonella dadayi and A. clathratula. We provide notes on
      the "Sars' Method", hatching of freshwater crustaceans from dry mud, a simple
      technique that complements the information of hit-and-run surveys. About half of
      the total species number (44%) was revived through this method; 18% of species
      were additional to field-collected samples. The Sars' method also yielded
      abundant specimens of rare species, useful for identification and studies on
      behaviour.

PMID- 21085783
TI  - Phytoplankton assemblages in a reservoir cascade of a large tropical -
      subtropical river (SE, Brazil).
AB  - The phytoplankton assemblages from eight reservoirs of the Paranapanema River
      were studied during two consecutive years. Chlorophyceae and Bacillaryophyceae
      dominated in richness. The observed high number of taxa, 234, reflects the
      extensive sampling programme and evidences the necessity of considering the whole
      hydrograph basin to assess the biodiversity status of inland water ecosystems.
      The dams had a negative effect on phytoplankton richness, with higher number of
      taxa associate to riverine (non-regulated) stretches. The tributary rivers also
      exhibited high species richness, showing the importance of considering the
      lateral dimension, in addition to the longitudinal one, for aquatic biota
      inventories in large river basins/reservoirs. Richness and diversity were also
      positively influenced by the connectivity with lateral wetlands (macrophyte
      dominated lakes) due to the periphyton influence. The phytoplankton
      abundance/biomass was not influenced by higher water retention time. Higher
      values occurred in the middle basin stretches (river-passage reservoirs) due to
      the increase in the trophic conditions. There was a positive correlation with
      phosphorus. Poorer light conditions in the cascade do not limit the phytoplankton
      biomass, with assemblages dominated by species tolerant to turbulent conditions
      and high mineral turbidity. Bacillariophyceae and Cryptophyceae dominated
      numerically. The first group (unicellular forms) was prominent in the large and
      oligotrophic upstream reservoirs. The second was highly abundant in the river
      passage (low retention time), and more eutrophic, reservoirs. Cyanophyceae growth
      is probably controlled by advection processes (wash-out effect). The zooplankton
      does not control the phytoplankton biomass and the diversity of both groups is
      positively associated in the cascade. The structure of the phytoplankton
      assemblages showed to be a good indicator of the operationally distinct
      reservoirs of the Paranapanema cascade and also reflected the changes in the
      trophic conditions along the basin.

PMID- 21085784
TI  - Limnological changes in Dom Helvecio Lake (South-East Brazil): natural and
      anthropogenic causes.
AB  - In order to verify changes in physical, chemical and biological features of Dom
      Helvecio Lake (South-East Brazil), this study compares previous and recent data
      obtained from limnological investigations over three decades. Plankton species
      composition and density together with environmental data from 1978, 1983, and
      during 1999 to 2006 showed changes driven by seasonal climatic forces or by
      anthropogenic causes. Changes in diversity are shown as a consequence of
      alternation of rainy and dry periods and introduction of exotic fish species.
      Finally, suggestions are made for improving conservation efforts in the area,
      through planned actions and monitoring programmes.

PMID- 21085785
TI  - Temporal coherence among tropical coastal lagoons: a search for patterns and
      mechanisms.
AB  - Temporal coherence (i.e., the degree of synchronicity of a given variable among
      ecological units within a predefined space) has been shown for several
      limnological features among temperate lakes, allowing predictions about the
      structure and function of ecosystems. However, there is little evidence of
      temporal coherence among tropical aquatic systems, where the climatic variability
      among seasons is less pronounced. Here, we used data from long-term monitoring of
      physical, chemical and biological variables to test the degree of temporal
      coherence among 18 tropical coastal lagoons. The water temperature and
      chlorophyll-a concentration had the highest and lowest temporal coherence among
      the lagoons, respectively, whereas the salinity and water colour had intermediate
      temporal coherence. The regional climactic factors were the main factors
      responsible for the coherence patterns in the water temperature and water colour,
      whereas the landscape position and morphometric characteristics explained much of
      the variation of the salinity and water colour among the lagoons. These results
      indicate that both local (lagoon morphometry) and regional (precipitation, air
      temperature) factors regulate the physical and chemical conditions of coastal
      lagoons by adjusting the terrestrial and marine subsidies at a landscape-scale.
      On the other hand, the chlorophyll-a concentration appears to be primarily
      regulated by specific local conditions resulting in a weak temporal coherence
      among the ecosystems. We concluded that temporal coherence in tropical ecosystems
      is possible, at least for some environmental features, and should be evaluated
      for other tropical ecosystems. Our results also reinforce that aquatic ecosystems
      should be studied more broadly to accomplish a full understanding of their
      structure and function.

PMID- 21085786
TI  - Cold fronts and reservoir limnology: an integrated approach towards the
      ecological dynamics of freshwater ecosystems.
AB  - In this paper the authors discuss the effects of cold fronts on the dynamics of
      freshwater ecosystems of southeast South America. Cold fronts originating from
      the Antarctic show a monthly frequency that promotes turbulence and vertical
      mixing in reservoirs with a consequence to homogenize nutrient distribution,
      dissolved oxygen and temperature. Weak thermoclines and the athelomixis process
      immediately before, during and after the passage of cold fronts interfere with
      phytoplankton succession in reservoirs. Cyanobacteria blooms in eutrophic
      reservoirs are frequently connected with periods of stratification and stability
      of the water column. Cold fronts in the Amazon and Pantanal lakes may produce
      fish killings during the process of "friagem" associated mixing events. Further
      studies will try to implement a model to predict the impact of cold fronts and
      prepare management procedures in order to cope with cyanobacteria blooms during
      warm and stable water column periods. Changes in water quality of reservoirs are
      expected during circulation periods caused by cold fronts.

PMID- 21085787
TI  - Occurrence of Ceratium furcoides (Levander) Langhans 1925 bloom at the Billings
      Reservoir, Sao Paulo State, Brazil.
AB  - An unusual bloom of Ceratium furcoides is reported for a station of the
      Taquacetuba compartment of the Billings Reservoir. The appearance of this bloom
      is attributed to the mixing and turbulence of the water column that removed
      Ceratium cysts from the surface of the sediment and promoted conditions for the
      growth of this species in the region of mixing. Cold fronts approaching the
      Billings Reservoir are probably the cause of the mixing and bloom. Also
      turbulence induced by wind increased phosphorus concentration in the water
      column. Ceratium furcoides was the dominant species at station 1 where the
      nutrient concentrations of nitrogen and phosphorus were high. Ceratium spp.
      blooms may be a problem for water treatment and massive mortality can affect the
      dissolved oxygen of the water producing fish kill.

PMID- 21085788
TI  - Modeling the potential distribution of the invasive golden mussel Limnoperna
      fortunei in the Upper Paraguay River system using limnological variables.
AB  - The invasive golden mussel, Limnoperna fortunei (Dunker, 1857), was introduced
      into the La Plata River estuary and quickly expanded upstream to the North, into
      the Paraguay and Parana rivers. An ecological niche modeling approach, based on
      limnological variables, was used to predict the expansion of the golden mussel in
      the Paraguay River and its tributaries. We used three approaches to predict the
      geographic distribution: 1) the spatial distribution of calcium concentration and
      the saturation index for calcium carbonate (calcite); 2) the Genetic Algorithm
      for Rule-Set Production (GARP) model; and the 3) Maximum Entropy Method (Maxent)
      model. Other limnological variables such as temperature, dissolved oxygen, pH,
      and Total Suspended Solids (TSS) were used in the latter two cases. Important
      tributaries of the Paraguay River such as the Cuiaba and Miranda/Aquidauana
      rivers exhibit high risk of invasion, while lower risk was observed in the
      chemically dilute waters of the middle basin where shell calcification may be
      limited by low calcium concentrations and carbonate mineral undersaturation.

PMID- 21085789
TI  - Cianobacterial bloom and animal mass mortality in a reservoir from Central
      Argentina.
AB  - Piedras Moras reservoir (32 degrees  10'27" S and 64 degrees  16' 29" W; 832 ha),
      integrates a series of artificial lakes belonging to the Rio Tercero basin
      (Cordoba, Argentina). During March 2009 an algal bloom occurred, coinciding with
      several animal species mortality, mainly wild birds. The goal of this work was to
      establish the trophic status of the reservoir in relation to that mortality.
      Variables were evaluated in situ (temperature and water transparency) and samples
      were taken in order to identify algal species, Chl-a concentration
      (spectrophotometry) and toxins - total microcystines- (inmuno-enzymatic assay,
      ELISA). Histopathology studies were made on Fulica sp. A strong heterogenity in
      water transparency was observed, and "patches" of Potamogeton berteroanus
      distributed all along the lake, with Secchi disk minimal and medium values of
      0.15 and 0.94 m. Chl-a concentration oscillated from 35.7 to 320.9 mg.m-3.
      Predominant phytoplankton species were Anabaena spiroides and Microcystis
      aeruginosa (Cyanophyceae). Water temperature was 27.8  degrees C (+/-0.88).
      Maximal value of total microcystine concentration was 0.23 MUg.L-1. Chl-a
      concentration at the moment when mass mortality occurred (2.022 mg.m-3), and
      histopathological observations, strongly suggest that the animals' death was due
      to cianotoxins.

PMID- 21085790
TI  - Five new species of genus Astyanax Baird & Girard, 1854 from Rio Iguacu, Parana,
      Brazil (Ostariophysi, Characiformes, Characidae).
AB  - Five new species of the Neotropical characiform genus Astyanax Baird & Girard are
      described from Rio Iguacu at the border of Parana and Santa Catarina states,
      southeastern Brazil and Astyanax gymnogenis Eigenmann is redescribed. Each new
      species can be distinguished from all other Astyanax species from the upper Rio
      Parana basin by exclusive combinations of: tooth shape, number of dental cuspids,
      distance between third infraorbital and preopercle, number of lateral line
      scales, longitudinal series of scales, number of gill-rakers and differences from
      shape of body and head traits. This study proposes the species of genus Astyanax
      from Rio Iguacu as probably endemic, since all of them are absent from
      tributaries of the Rio Parana hydrographic system. The high degree of
      diversification acquired by those Astyanax species in the Iguacu basin may
      perhaps be allied to the long isolation period of this river from the Rio Parana
      basin caused by the Iguacu waterfalls. This barrier probably isolated those
      basins resulting in original groups of Characiformes and then Astyanax species,
      both isolated from one another and both different from their relatives in
      neighbouring basins.

PMID- 21085791
TI  - A new species of Notodiaptomus Kiefer (Crustacea, Copepoda, Calanoida,
      Diaptomidae) from Brazil.
AB  - Description of a new species of Diaptomidae (Crustacea, Copepoda, Calanoida)
      Notodiaptomus oliveirai is given from the material obtained at a reservoir at
      Barra Bonita, SP in 1992. The new species is very similar to Notodiaptomus
      henseni Dahl 1894 although both species can be found in the same locality,
      constituting two distinct populations. Notodiaptomus oliveirai seems to be
      endowed with great adaptability to changes in environmental conditions, extending
      its distribution to all the hydrographic basins in the state of Sao Paulo.

PMID- 21085792
TI  - Anurofauna of an Atlantic Rainforest fragment and its surroundings in Northern
      Rio de Janeiro State, Brazil.
AB  - We carried out a study on the anurofaunal community from an Atlantic Forest
      fragment (Monte Verde mountains) and the surrounding area in Cambuci
      municipality, Rio de Janeiro State, Brazil, which constitutes one of the largest
      fragments remaining in the largely deforested landscape of the northern portion
      of the State. We combined three sampling methods: plot sampling, transects and
      pit-fall traps. We recorded twenty species of amphibians, of which only eleven
      were found within the forest fragment (and five of these also occurred in the
      surrounding matrix). Two of the species recorded in the present study
      (Crossodactylus sp. and Ischnocnema cf. parva) may represent undescribed taxa.
      Our records expand the distribution range of one species (Scinax trapicheiroi) to
      the north, and fill a geographic distribution gap for another one (Ischnocnema
      oea). The estimated overall density of frogs living in the leaf litter of the
      fragment (based on results of plot sampling) was 3.1 individuals/100 m2, with
      Haddadus binotatus being the most abundant species (2.4 individuals/100 m2).
      Comparisons of our data with those of other studies suggest that anuran
      communities in forest fragments ca. 1,000 ha or smaller may be severely limited
      in their richness, and often include a large proportion of species tolerant to
      open areas, such as many hylids. Our results show the importance of increasing
      knowledge about the anurofaunal community of the northern portion of the State of
      Rio de Janeiro and preserve the forest remnants that still exist in the region.

PMID- 21085793
TI  - Biomass and production of Cladocera in Furnas Reservoir, Minas Gerais, Brazil.
AB  - Secondary production of zooplankton, the main energy pathway in many aquatic
      ecosystems, is crucial to an Understanding of functioning of these systems
      function. In this study, we analyzed the magnitude and seasonal variations of the
      population density, biomass and secondary production of Cladocera in the Furnas
      Reservoir (Brazil). Samples were carried out monthly at 6 points in the
      reservoir, from August 2006 to July 2007. Main physical and chemical variables in
      the water column were measured in situ. Data on density, biomass and development
      times were obtained and used to calculate the secondary production of eight
      Cladocera species. The total production of Cladocera varied from 0.02 to 28.6
      mgDWm-3.day-1, among the sampling sites. The highest values were recorded in
      spring and summer months (September to January), and were correlated to the
      increase in the biomass of the phytoplankton. The mean production:biomass ratio
      was 0.32. The level of production in Furnas Reservoir fell within the range of
      those reported in the literature and was of the same order of magnitude of the
      production values recorded for oligotrophic reservoirs. Cladocera production
      differed spatially inside the Sapucai compartment and also in the temporal scale,
      seasonally.

PMID- 21085794
TI  - Influence of indomethacin on the regenerative process of the tail fin of teleost:
      morphometric and ultrastructural analysis.
AB  - When partially amputated or severely injured, teleost fins suffer a regenerative
      process called epimorphic regeneration characterised by the following stages: the
      formation of a multistratified epidermal layer, the disorganisation and distal
      migration of multipotent mesenchymal cells, the proliferation of these cells in
      order to form the blastema, continuous proliferation of distal blastema to
      facilitate the growth, and differentiation of the proximal blastema in order to
      restore its lost structure. The regeneration of the fin is extremely sensitive to
      the action of some drugs that can interfere in its structure restoration. For
      this reason, and also based on papers relating that indomethacin can interfere
      somehow in the tissue restoration of many different organisms, the aim of this
      work is to evaluate the possible effects of this drug in three different doses in
      the regeneration of the teleost fish tail fin, taking into consideration the
      synthesis, the disposition and organisation of lepidotrichial matrix components,
      the restoration of actinotrichia, as well as the fin area itself. Therefore,
      histochemical, ultrastructural and morphometric analysis were done and it was
      observed that indomethacin in doses of 20 and 30 mg.L-1 caused a delay in the
      regenerative process of the dermal skeleton (lepidotrichia and actinotrichia) of
      the tail fins. These doses could have interfered, momentarily, in the process of
      blastemal cell differentiation in the cells responsible for the synthesis and
      disposition of actinotrichia and lepidotrichia or, even interfered in the
      signalling necessary for the recent differentiated cells to begin synthesising
      the components of the dermal skeleton.

PMID- 21085795
TI  - Macroinvertebrates in low-order streams in two fragments of Atlantic Forest in
      different states of conservation, in the State of Sao Paulo (Brazil).
AB  - The presence of a riparian forest is one of the main factors that act directly on
      the ecology of a fluvial system, and the relation of the forest and the lotic
      environments might have an important influence on the distribution of the
      macroinvertebrates. In this context, the benthic macroinvertebrate communities in
      four low-order streams in Sao Paulo (Brazil) were analysed, with the aim of
      assessing the state of recovery of the surrounding forest fragments. The benthic
      organisms were sampled in the winter, a period of low rainfall. Of the 6,331
      specimens of macroinvertebrates collected, 124 taxa belonging to 48 families were
      identified. The results showed greater diversity in the Canchim Farm streams and
      greater abundance in the Lake Park streams. Cluster analysis showed that the
      stream Canchim distanced itself from the others, being considered reference.

PMID- 21085796
TI  - Examining the role of microvesicles to develop prognostic and diagnostic assays.

PMID- 21085797
TI  - Dental caries profile in Monte Negro, Amazonian state of Rondonia, Brazil, in
      2008.
AB  - OBJECTIVE: This epidemiological survey assessed the dental caries profile in
      Monte Negro, a small town in the Amazonian state of Rondonia, Brazil, and its
      relationship with the northern region, national and global goals for oral health
      in the years 2000 and 2020. MATERIAL AND METHODS: The groups randomly examined
      were composed of individuals aged 5, 12, 15 to 19, 35 to 44, 65 to 74 years,
      living in both rural and urban areas. RESULTS: The means dft (standard deviation)
      and DMFT (standard deviation) for the groups were, respectively, 3.15 (3.12),
      3.41 (2.69), 5.96 (4.19), 16.00 (7.30) and 25.96 (9.82). Caries-free individuals
      were 34.42%, 14.81% and 8.16% in the preschoolchildren, schoolchildren and
      adolescent groups, respectively. The Significant Caries Index percentages applied
      to the two younger groups were 6.65 and 6.70, and they increased to 32.00 in the
      individuals aged 65 to 74 years. Care Index percentages for adolescents, adults
      and elderly groups were, respectively, 29.40, 25.00 and 1.41. The dental caries
      profile in Monte Negro in 2008 shows that, 8 years after the year 2000, no
      FDI/WHO goal for any age settled in 1982 has been achieved. Dental caries
      increased with age and the main dental problem of adult and elderly groups was
      tooth loss. CONCLUSION: Oral health promotion and prevention of oral disease
      policies are urgent needs. Setting of oral health goals and targets to people
      living in Monte Negro or Amazonia to be pursuit and achieved in a near future is
      an important action to do because of the culture, sanitary conditions and
      socioeconomic aspects of this particular population.

PMID- 21085799
TI  - Sexual harassment in dentistry: prevalence in dental school.
AB  - OBJECTIVE: Sexual harassment is unlawful in all work and educational environments
      in most nations of the world. The goals of this study were to describe the sexual
      harassment prevalence and to evaluate the experiences and attitudes of
      undergraduate students in one dental school in Brazil. MATERIAL AND METHODS: An
      18-item questionnaire was administered to 254 dental students with a completion
      rate of 82% (208). Students were requested to respond to questions about their
      background and academic level in dental school, their personal experiences with
      sexual harassment and their observation of someone else being sexually harassed.
      Bivariate statistical analyses were performed. RESULTS: Fifteen percent of the
      students reported being sexually harassed by a patient, by a relative of a
      patient or by a professor. Male students had 3 times higher probability of being
      sexually harassed than female student [OR=2.910 (1.113-7.611)]. Additionally,
      25.4% of the students reported witnessing sexual harassment at the school
      environment. The majority of students did not feel professionally prepared to
      respond to unwanted sexual behaviors. CONCLUSION: These findings demonstrate that
      sexual harassment can occur in a dental school setting. There is a need for
      ongoing sexual harassment education programs for students and university staff.
      Increased knowledge of sexual harassment during graduation can better prepare
      dental professionals to respond to sexual harassment during their practice.

PMID- 21085798
TI  - A critical analysis of the degree of conversion of resin-based luting cements.
AB  - OBJECTIVE: This study analyzed the degree of conversion (DC%) of four resin-based
      cements (All Ceram, Enforce, Rely X ARC and Variolink II) activated by two modes
      (chemical and dual), and evaluated the decrease of DC% in the dual mode promoted
      by the interposition of a 2.0-mm-thick IPS Empress 2 disc. MATERIAL AND METHODS:
      In the chemical activation, the resin-based cements were prepared by mixing equal
      amounts of base and catalyst pastes. In the dual activation, after mixing, the
      cements were light-activated at 650 mW/cm2 for 40 s. In a third group, the
      cements were light-activated through a 2.0-mm-thick IPS Empress 2 disc. The DC%
      was evaluated in a FT-IR spectrometer equipped with an attenuated total
      reflectance crystal (ATR). The data were analyzed by two-way ANOVA and Tukey's
      HSD test. RESULTS: For all resin-based cements, the DC% was significantly higher
      with dual activation, followed by dual activation through IPS Empress 2, and
      chemical activation (p<0.05). Irrespective of the activation mode, Rely X
      presented the highest DC% (p<0.05). Chemically activated Variolink and All Ceram
      showed the worst results (p<0.05). The DC% decreased significantly when
      activation was performed through a 2.0-mm-thick IPS Empress 2 disc (p<0.05).
      CONCLUSION: The results of the present study suggest that resin-based cements
      could present low DC% when the materials are dually activated through 2.0 mm of
      reinforced ceramic materials with translucency equal to or less than that of IPS
      Empress 2.

PMID- 21085800
TI  - Cariostatic effect of fluoride-containing restorative materials associated with
      fluoride gels on root dentin.
AB  - Secondary caries is still the main cause of restoration replacement, especially
      on the root surface. OBJECTIVE: This in vitro study evaluated the cariostatic
      effects of fluoride-containing restorative materials associated with fluoride
      gels, on root dentin. MATERIALS AND METHODS: A randomized complete block design
      was used to test the effects of the restorative systems, fluoride regimes and the
      interactions among them at different distances from restoration margins.
      Standardized cavities were prepared on 240 bovine root specimens and randomly
      assigned to 15 groups of treatments (n=16). Cavities were filled with the
      following restorative materials: Ketac-Fil (3M-ESPE); Vitremer (3M-ESPE);
      Dyract/Prime & Bond NT (Dentsply); Charisma/Gluma One Bond (Heraeus Kulzer) and
      the control, Z250/Single Bond (3M-ESPE). The specimens were subjected to a pH
      cycling model designed to simulate high-caries activity. During the cycles, 1.23%
      acidulated phosphate fluoride, 2.0% neutral sodium fluoride or
      deionized/distilled water (control) was applied to the specimens for 4 min. The
      surface Knoop microhardness test was performed before (KHNi) and after (KHNf) the
      pH cycles at 100, 200 and 300 mm from the margins. Dentin microhardness loss was
      represented by the difference in initial and final values (KHNi - KHNf). Data
      were analyzed by Friedman's and Wilcoxon's tests, ANOVA and Tukey's test
      (alpha=5%). RESULTS: The interaction of restorative systems and topical
      treatments was not significant (p=0.102). Dentin microhardness loss was lowest
      closer to the restoration. Ketac-fil presented the highest cariostatic effect.
      Vitremer presented a moderate effect, while Dyract and Charisma did not differ
      from the control, Z250. The effects of neutral and acidulated fluoride gels were
      similar to each other and higher than the control. CONCLUSION: Conventional and
      resin-modified glass ionomer cements as well as neutral and acidulated fluoride
      gels inhibit the progression of artificial caries adjacent to restorations. The
      associated effect of fluoride-containing restorative materials and gels could not
      be demonstrated.

PMID- 21085801
TI  - Effects of light-curing time on the cytotoxicity of a restorative composite resin
      on odontoblast-like cells.
AB  - This in vitro study evaluated the cytotoxicity of an experimental restorative
      composite resin subjected to different light-curing regimens. METHODS: Forty
      round-shaped specimens were prepared and randomly assigned to four experimental
      groups (n=10), as follows: in Group 1, no light-curing; in Groups 2, 3 and 4, the
      composite resin specimens were light-cured for 20, 40 or 60 s, respectively. In
      Group 5, filter paper discs soaked in 5 uL PBS were used as negative controls.
      The resin specimens and paper discs were placed in wells of 24-well plates in
      which the odontoblast-like cells MDPC-23 (30,000 cells/cm2) were plated and
      incubated in a humidified incubator with 5% CO2 and 95% air at 37oC for 72 h. The
      cytotoxicity was evaluated by the cell metabolism (MTT assay) and cell morphology
      (SEM). The data were analyzed statistically by Kruskal-Wallis and Mann-Whitney
      tests (p<0.05). RESULTS: In G1, cell metabolism decreased by 86.2%, indicating a
      severe cytotoxicity of the non-light-cured composite resin. On the other hand,
      cell metabolism decreased by only 13.3% and 13.5% in G2 and G3, respectively. No
      cytotoxic effects were observed in G4 and G5. In G1, only a few round-shaped
      cells with short processes on their cytoplasmic membrane were observed. In the
      other experimental groups as well as in control group, a number of spindle-shaped
      cells with long cytoplasmic processes were found. CONCLUSION: Regardless of the
      photoactivation time used in the present investigation, the experimental
      composite resin presented mild to no toxic effects to the odontoblast-like MDPC
      23 cells. However, intense cytotoxic effects occurred when no light-curing was
      performed.

PMID- 21085802
TI  - Radiodensity evaluation of dental impression materials in comparison to tooth
      structures.
AB  - In the most recent decades, several developments have been made on impression
      materials' composition, but there are very few radiodensity studies in the
      literature. It is expected that an acceptable degree of radiodensity would enable
      the detection of small fragments left inside gingival sulcus or root canals.
      OBJECTIVE: The aim of this study was to determine the radiodensity of different
      impression materials, and to compare them to human and bovine enamel and dentin.
      MATERIAL AND METHODS: Twenty-five impression materials, from 5 classes, were
      studied: addition and condensation silicones, polyether, polysulfides and
      alginates. Five 1-mm-thick samples of each material and tooth structure were
      produced. Each sample was evaluated 3 times (N=15), being exposed to x-ray over a
      phosphor plate of Digora digital system, and radiodensity was obtained by the
      software Digora for Windows 2.5 Rev 0. An aluminum stepwedge served as a control.
      Data were subjected to Kruskal-Wallis and Dunn's method (alpha=0.05). RESULTS:
      Different materials and respective classes had a different behavior with respect
      to radiodensity. Polysulfides showed high values of radiodensity, comparable to
      human enamel (p>0.05), but not to bovine enamel (p<0.05). Human dentin was
      similar only to a heavy-body addition silicon material, but bovine dentin was
      similar to several materials. Generally, heavy-body materials showed higher
      radiodensity than light-body ones (p<0.05). CONCLUSION: Impression materials'
      radiodensity are influenced by composition, and almost all of them would present
      a difficult detection against enamel or dentin background in radiographic
      examinations.

PMID- 21085803
TI  - The adhesive system and root canal region do not influence the degree of
      conversion of dual resin cement.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of two adhesive
      systems and the post space region on the degree of conversion of dual resin
      cement and its bond strength to root dentin. MATERIAL AND METHODS: One three-step
      etch-and-rinse (All-bond 2, Bisco) and another one-step self-etch (Xeno III,
      Dentsply) adhesive systems were applied on 20 (n=10) crownless bovine incisors,
      at 12-mm-deep post space preparation, and a fiber post (DT Light Post, Bisco) was
      cemented using a dual cure resin cement (Duo-Link, Bisco). Three transverse
      sections (3 mm) were obtained, being one from each study region (cervical, middle
      and apical). The degree of conversion of the dual cure resin cement was
      determined by a micro-Raman spectrometer. The data (%) were submitted to repeated
      measures analysis of variance and Tukey's test (p<0.05). RESULTS: For both
      groups, the degree of conversion means (%) (All bond 2cervical = 69.3; All bond
      2middle = 55.1; All bond 2apical= 56; Xeno IIIcervical = 68.7; Xeno IIImiddle =
      68.8; Xeno IIIapical = 54.3) were not significantly different along the post
      space regions (p<0.05). CONCLUSION: Neither the adhesive nor the post space
      region influenced the degree of conversion of the cement layer.

PMID- 21085804
TI  - Transcriptional analysis of the human PAX9 promoter.
AB  - OBJECTIVES: PAX9 belongs to the Pax family of transcriptional factor genes. This
      gene is expressed in embryonic tissues such as somites, pharyngeal pouch
      endoderm, distal limb buds and neural crest-derived mesenchyme. Polymorphisms in
      the upstream promoter region of the human PAX9 have been associated with human
      non-syndromic tooth agenesis. In the present study, we verified the in vitro mRNA
      expression of this gene and the luciferase activity of two constructs containing
      promoter sequences of the PAX9 gene. MATERIAL AND METHODS: Embryonic tissues were
      obtained from digits, face, and midbrain/hindbrain regions. Fragments containing
      PAX9 promoter sequences were cloned into reporter plasmids and were transfected
      into the different cell cultures. mRNA were extracted from primary cell cultures.
      RESULTS: The semi-quantitative RT-PCR results showed that in vitro E13.5 limb bud
      and CNS cells express PAX9, but cells derived from the facial region do not.
      Moreover, the luciferase assay showed that protein activity of the constructed
      vector was weaker than pgl3 -basic alone. CONCLUSIONS: The present results
      suggest that the promoter sequences analyzed are not sufficient to drive PAX9
      gene transcription.

PMID- 21085805
TI  - Comparative study of two commercially pure titanium casting methods.
AB  - The interest in using titanium to fabricate removable partial denture (RPD)
      frameworks has increased, but there are few studies evaluating the effects of
      casting methods on clasp behavior. OBJECTIVE: This study compared the occurrence
      of porosities and the retentive force of commercially pure titanium (CP Ti) and
      cobalt-chromium (Co-Cr) removable partial denture circumferential clasps cast by
      induction/centrifugation and plasma/vacuum-pressure. MATERIAL AND METHODS: 72
      frameworks were cast from CP Ti (n=36) and Co-Cr alloy (n=36; control group). For
      each material, 18 frameworks were casted by electromagnetic induction and
      injected by centrifugation, whereas the other 18 were casted by plasma and
      injected by vacuum-pressure. For each casting method, three subgroups (n=6) were
      formed: 0.25 mm, 0.50 mm, and 0.75 mm undercuts. The specimens were radiographed
      and subjected to an insertion/removal test simulating 5 years of framework use.
      Data were analyzed by ANOVA and Tukey's to compare materials and cast methods
      (alpha=0.05). RESULTS: Three of 18 specimens of the induction/centrifugation
      group and 9 of 18 specimens of plasma/vacuum-pressure cast presented porosities,
      but only 1 and 7 specimens, respectively, were rejected for simulation test. For
      Co-Cr alloy, no defects were found. Comparing the casting methods, statistically
      significant differences (p<0.05) were observed only for the Co-Cr alloy with 0.25
      mm and 0.50 mm undercuts. Significant differences were found for the 0.25 mm and
      0.75 mm undercuts dependent on the material used. For the 0.50 mm undercut,
      significant differences were found when the materials were induction casted.
      CONCLUSION: Although both casting methods produced satisfactory CP Ti RPD
      frameworks, the occurrence of porosities was greater in the plasma/vacuum
      pressure than in the induction/centrifugation method, the latter resulting in
      higher clasp rigidity, generating higher retention force values.

PMID- 21085806
TI  - Evaluation of two morphometric methods of bone loss percentages caused by
      periodontitis in rats in different locations.
AB  - OBJECTIVE: The present study evaluated morphometrically bone loss percentages in
      experimental periodontitis in rats, comparing different locations (lingual
      mandible, palatal maxilla and buccal maxilla) and two evaluation methods
      (distance and area methods). MATERIAL AND METHODS: Ligatures were placed around
      the maxillary right second molar and around the mandibular right first molar in
      14 female Wistar rats. The contralateral molars served as intragroup controls.
      After 4 weeks, the rats were sacrificed and their mandible and maxilla were
      removed. The specimens were dissected and stained with methylene blue dye. Bone
      loss was evaluated by two different methods on the surfaces of the defleshed jaw.
      In the first method, the distance from the cementoenamel junction (CEJ) to the
      alveolar bone crest was measured in the roots of teeth associated with ligature.
      In the second method, the area of bone loss was determined using the alveolar
      tissue bone, CEJ and the proximal region of roots associated with the ligature as
      reference. The data were converted to bone loss percentages caused by ligature:
      (ligated - unligated) x 100/ligated. RESULTS: When comparing the distance and
      area methods, no statistically significant difference was observed (p>0.05). Both
      methodologies indicated that the maxilla presented greater bone loss than the
      mandible and it was more accentuated on the buccal side than on the palatal side
      (p<0.05). CONCLUSIONS: The findings of this study show that both the area and the
      distance methods can be used to evaluate bone loss caused by ligature placement
      in rats, and suggest applying the morphometric methodology to the maxilla on the
      buccal side.

PMID- 21085807
TI  - Biocompatibility of orthodontic adhesives in rat subcutaneous tissue.
AB  - OBJECTIVE: The objective of the present study was to verify the hypothesis that
      no difference in biocompatibility exists between different orthodontic adhesives.
      MATERIAL AND METHODS: Thirty male Wistar rats were used in this study and divided
      into five groups (n=6): Group 1 (control, distilled water), Group 2 (Concise),
      Group 3 (Xeno III), Group 4 (Transbond XT), and Group 5 (Transbond plus Self
      Etching Primer). Two cavities were performed in the subcutaneous dorsum of each
      animal to place a polyvinyl sponge soaked with 2 drops of the respective adhesive
      in each surgical loci. Two animals of each group were sacrificed after 7, 15, and
      30 days, and their tissues were analyzed by using an optical microscope. RESULTS:
      At day 7, Groups 3 (Transbond XT) and 4 (Xeno III) showed intense mono- and
      polymorphonuclear inflammatory infiltrate with no differences between them,
      whereas Groups 1 (control) and 2 (Concise) showed moderate mononuclear
      inflammatory infiltrate. At day 15, severe inflammation was observed in Group 3
      (Transbond XT) compared to other groups. At day 30, the same group showed a more
      expressive mononuclear inflammatory infiltrate compared to other groups.
      CONCLUSION: Among the orthodontic adhesive analyzed, it may be concluded that
      Transbond XT exhibited the worst biocompatibility. However, one cannot interpret
      the specificity of the data generated in vivo animal models as a human response.

PMID- 21085808
TI  - Evaluation of the antimicrobial effect of super-oxidized water (Sterilox(r)) and
      sodium hypochlorite against Enterococcus faecalis in a bovine root canal model.
AB  - Ideally root canal irrigants should have, amongst other properties, antimicrobial
      action associated with a lack of toxicity against periapical tissues. Sodium
      hypochlorite (NaOCl) is a widely used root canal irrigant, however it has been
      shown to have a cytotoxic effect on vital tissue and therefore it is prudent to
      investigate alternative irrigants. Sterilox's Aquatine Alpha Electrolyte(r)
      belongs to the group of the super-oxidized waters; it consists of a mixture of
      oxidizing substances, and has been suggested to be used as root canal irrigant.
      Super-oxidized waters have been shown to provide efficient cleaning of root canal
      walls, and have been proposed to be used for the disinfection of medical
      equipment. OBJECTIVE: To compare the antimicrobial action against Enterococcus
      faecalis of NaOCl, Optident Sterilox Electrolyte Solution(r) and Sterilox's
      Aquatine Alpha Electrolyte(r) when used as irrigating solutions in a bovine root
      canal model. METHODOLOGY: Root sections were prepared and inoculated with E.
      faecalis JH2-2. After 10 days of incubation the root canals were irrigated using
      one of three solutions (NaOCl, Optident Sterilox Electrolyte Solution(r)and
      Sterilox's Aquatine Alpha Electrolyte(r)) and subsequently sampled by grinding
      dentin using drills. The debris was placed in BHI broth and dilutions were plated
      onto fresh agar plates to quantify growth. RESULTS: Sodium hypochlorite was the
      only irrigant to eliminate all bacteria. When the dilutions were made, although
      NaOCl was still statistically superior, Sterilox's Aquatine Alpha Electrolyte(r)
      solution was superior to Optident Sterilox Electrolyte Solution(r). CONCLUSIONS:
      Under the conditions of this study Sterilox's Aquatine Alpha Electrolyte(r)
      appeared to have significantly more antimicrobial action compared to the Optident
      Sterilox Electrolyte Solution(r) alone, however NaOCl was the only solution able
      to consistently eradicate E. faecalis in the model.

PMID- 21085809
TI  - Postmortem acinar autolysis in rat sublingual gland: a morphometric study.
AB  - OBJECTIVE: To analyze and to quantify morphological acinar postmortem changes in
      rat sublingual glands (SLG). MATERIAL AND METHODSs: Fifty rats were divided into
      two groups of 25 animals each. Group I was used for morphological and
      morphometric evaluations and group II for the determination of gland density and
      processed gland volume. Acinar autolytic changes were studied at 0 (control
      group), 3, 6, 12 and 24 h postmortem periods. The morphometric analysis of the
      volume density (Vv) and total volume (Vt) of intact (ia) and autolyzed (aa) acini
      was performed under light microscopy using a Zeiss II integration grid with 100
      symmetrically distributed points. RESULTS: Morphologically, temporal progressive
      nuclear alterations and gradual loss of the structural architecture of acinar
      cells were found. Regarding quantitative results, both the Vvaa and the Vvia
      showed statistically significant differences among all postmortem periods
      (p<0.05). Vvaa increased from 0.42% at 0 h to 75.84% at 24 h postmortem and Vvia
      decreased from 71.16% to 0% over the same period. For Vtaa and Vtia, no
      statistically significant differences occurred between 12-24 h and 0-3 h
      (p>0.05), respectively. Vtaa increased from 0.18 mm3 at 0 h to 38.17 mm3 at 12 h,
      while Vtia showed a decrease from 33.47 mm3 to 0 mm3 between 3-24 h postmortem.
      Data concerning Vtaa were adjusted by two-variable linear regression, obtaining
      the equation: y=-3.54+3.38x (r2=0.90). The Vtaa growth rate calculated by this
      equation was 3.38 mm3/h between 0-12 h. CONCLUSION: Acinar autolysis on rat SLG
      demonstrated the most significant signs during the first 6 h postmortem and was
      widely spread through the gland at 12 h.

PMID- 21085811
TI  - Temperature change in pig rib bone during implant site preparation by low-speed
      drilling.
AB  - OBJECTIVES: The purpose of this study was to evaluate the temperature change
      during low-speed drilling using infrared thermography. MATERIAL AND METHODS: Pig
      ribs were used to provide cortical bone of a similar quality to human mandible.
      Heat production by three implant drill systems (two conventional drilling systems
      and one low-speed drilling system) was evaluated by measuring the bone
      temperature using infrared thermography. Each system had two different bur sizes.
      The drill systems used were twist drill (2.0 mm/2.5 mm), which establishes the
      direction of the implant, and finally a 3.0 mm-pilot drill. Thermal images were
      recorded using the IRI1001 system (Infrared Integrated Systems Ltd.). Baseline
      temperature was 31+/-1oC. Measurements were repeated 10 times, and a static load
      of 10 kg was applied while drilling. Data were analyzed using descriptive
      statistics. Statistical analysis was conducted with two-way ANOVA. RESULTS AND
      CONCLUSIONS: Mean values (n=10 drill sequences) for maximum recorded temperature
      (Max ToC), change in temperature (DeltaToC) from baseline were as follows. The
      changes in temperature (DeltaToC) were 1.57oC and 2.46oC for the lowest and the
      highest values, respectively. Drilling at 50 rpm without irrigation did not
      produce overheating. There was no significant difference in heat production
      between the 3 implant drill systems (p>0.05). No implant drill system produced
      heat exceeding 47oC, which is the critical temperature for bone necrosis during
      low-speed drilling. Low-speed drilling without irrigation could be used during
      implant site preparation.

PMID- 21085810
TI  - Staining and calculus formation after 0.12% chlorhexidine rinses in plaque-free
      and plaque covered surfaces: a randomized trial.
AB  - OBJECTIVES: Studies concerning side effects of chlorhexidine as related to the
      presence of plaque are scarce. The purpose of this study was to compare the side
      effects of 0.12% chlorhexidine gluconate (CHX) on previously plaque-free (control
      group) and plaque-covered surfaces (test group). METHODS: This study had a single
      blind, randomized, split-mouth, 21 days-experimental gingivitis design, including
      20 individuals who abandoned all mechanical plaque control methods during 25
      days. After 4 days of plaque accumulation, the individuals had 2 randomized
      quadrants cleaned, remaining 2 quadrants with plaque-covered dental surfaces. On
      the fourth day, the individuals started with 0.12% CHX rinsing lasting for 21
      days. Stain index intensity and extent as well as calculus formation were
      evaluated during the experimental period. RESULTS: Intergroup comparisons showed
      statistically higher (p<0.05) stain intensity and extent index as well as
      calculus formation over the study in test surfaces as compared to control
      surfaces. Thus, 26.19% of test surfaces presented calculus, whereas calculus was
      observed in 4.52% in control surfaces. CONCLUSIONS: The presence of plaque
      increased 0.12% CHX side effects. These results strengthen the necessity of
      biofilm disruption prior to the start of CHX mouthrinses in order to reduce side
      effects.

PMID- 21085812
TI  - Effect of the simulated periodontal ligament on cast post-and-core removal using
      an ultrasonic device.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of simulated
      periodontal ligament (SPDL) on custom cast dowel and core removal by ultrasonic
      vibration. MATERIAL AND METHODS: Thirty-two human maxillary canines were included
      in resin cylinders with or without SPDL made from polyether impression material.
      In order to allow tensile testing, the roots included in resin cylinders with
      SPDL were fixed to cylinders with two stainless steel wires. Post-holes were
      prepared by standardizing the length at 8 mm and root canal impressions were made
      with self-cured resin acrylic. Cast dowel and core sets were fabricated and luted
      with Panavia F resin cement. Half of the samples were submitted to ultrasonic
      vibration before the tensile test. Data were analyzed statistically by two-way
      ANOVA and Tukey's post-hoc tests (p<0.05). RESULTS: The ultrasonic vibration
      reduced the tensile strength of the samples directly included in resin cylinders.
      There was no difference between the values, whether or not ultrasonic vibration
      was used, when the PDL was simulated. However, the presence of SPDL affected the
      tensile strength values even when no ultrasonic vibration was applied.
      CONCLUSION: Simulation of PDL has an effect on both ultrasonic vibration and
      tensile testing.

PMID- 21085813
TI  - Diclofenac in hyaluronic acid gel: an alternative treatment for actinic
      cheilitis.
AB  - OBJECTIVE: Actinic cheilitis (AC) is a precancerous lesion of the lip vermillion
      caused by prolonged exposure to ultraviolet light. The aim of this study was to
      evaluate the effect of 3% diclofenac in 2.5% hyaluronic acid gel in the treatment
      of AC. METHODS: Thirty-four patients with chronic AC were treated twice a day
      with topical diclofenac during a period of 30 to 180 days. The individuals were
      followed up every 15 days by means of clinical examination and digital
      photographic documentation. RESULTS: Of the 27 patients that completed the study,
      12 (44%) showed complete remission of the whitish plaques and exfoliative areas,
      and 15 (56%) had partial remission of the clinical picture of cheilitis. The
      latter group was submitted to excision of the leukoplakic areas which diagnosis
      varied from mild to moderate epithelial dysplasia. CONCLUSIONS: The results
      suggest a promising role for diclofenac in hyaluronic acid gel in the treatment
      of AC. This treatment has the advantages of not being invasive and showing few
      side effects.

PMID- 21085814
TI  - Pyogenic granuloma on the upper lip: an unusual location.
AB  - Pyogenic granuloma (PG) is a benign non-neoplastic mucocutaneous lesion. It is a
      reactional response to constant minor trauma and might be related to hormonal
      changes. In the mouth, PG is manifested as a sessile or pedunculated, resilient,
      erythematous, exophytic and painful papule or nodule with a smooth or lobulated
      surface that bleeds easily. PG preferentially affects the gingiva, but may also
      occur on the lips, tongue, oral mucosa and palate. The most common treatment is
      surgical excision. This paper describes a mucocutaneous PG on the upper lip,
      analyzing the clinical characteristics and discussing the features that
      distinguish this lesion from other similar oral mucosa lesions. The diagnosis of
      oral lesions is complex and leads the dentist to consider distinct lesions with
      different diagnostic methods. This case report with a 4 year-follow-up calls the
      attention to the uncommon mucocutaneous labial location of PG and to the fact
      that surgical excision is the safest method for diagnosis and treatment of PG of
      the lip, even when involving the mucosa and skin.

PMID- 21085815
TI  - Perception of asthma symptoms.

PMID- 21085816
TI  - Prevalence of and risk factors for wheezing in the first year of life.
AB  - OBJECTIVE: To determine the prevalence of and the risk factors for wheezing in
      infants under one year of age and residing in the city of Porto Alegre, Brazil.
      METHODS: This was a cross-sectional study and is part of a multicenter,
      multinational project. The parents or legal guardians of the infants were
      interviewed at primary health care clinics or during home visits. We used a
      standardized questionnaire, validated for use in Brazil. Potential risk factors
      were assessed by means of a Poisson regression model with robust variance
      estimation, using the Wald test to determine the significance of each variable in
      the model. RESULTS: The sample comprised 1,013 infants. The majority of those
      were male (53%), and the mean age was 13.5 +/- 1.2 months. In 61% of the infants,
      there had been at least one episode of wheezing, which had recurred at least
      three times in one third of those infants. The mean age at the first episode of
      wheezing was 5.16 months (median, 5 months). Over 40% of the infants with
      wheezing visited emergency rooms due to wheezing, and 17% of those were
      hospitalized at least once in the first year of life because of this symptom. In
      the multivariate analysis, the risk factors for wheezing were as follows: male
      gender; history of pneumonia; maternal smoking during pregnancy; day care center
      attendance; low maternal level of education; early weaning; multiple episodes of
      cold; first viral infection prior to 3 months of age; existence of siblings; and
      history of asthma in the nuclear family. CONCLUSIONS: The prevalence of wheezing
      is high among infants in the city of Porto Alegre. We identified various risk
      factors for wheezing in infants.

PMID- 21085817
TI  - Performance of a word labeled visual analog scale in determining the degree of
      dyspnea during exercise-induced bronchoconstriction in children and adolescents
      with asthma.
AB  - OBJECTIVE: There is an indirect relationship between airway obstruction in asthma
      and the intensity of breathlessness (dyspnea). A word labeled visual analog
      dyspnea scale with a 0-3 score has been widely used for the assessment of the
      degree of bronchoconstriction, although the perception of such obstruction varies
      considerably. The objective of this study was to determine whether children and
      adolescents are able to perceive acute exercise-induced bronchoconstriction
      (EIB), as well as to measure the discriminatory power of a word labeled visual
      analog dyspnea scale in relation to the intensity of the EIB. METHODS: A cross
      sectional study involving 134 children and adolescents with asthma and submitted
      to a six-minute steady-state exercise test on a cycle ergometer. The intensity of
      dyspnea was determined using a word labeled visual analog dyspnea scale prior to
      each determination of FEV1. The scale is scored from 0 to 3, with a logical
      sequence of pictures, ranging from "no symptoms" to "severe dyspnea". Variables
      were determined at baseline, as well as at 5, 10, and 20 min after the exercise
      test. The accuracy of the dyspnea scale in identifying the degree of EIB was
      determined by means of ROC curves for the post-exercise fall in FEV1, using cut
      off points of 10%, 20%, 30%, and 40%. RESULTS: Of the patients selected, 111
      finished the study, and 52 (46.8%) presented with EIB. The area under the ROC
      curve increased in direct proportion to increases in the degree of
      bronchoconstriction. CONCLUSIONS: Among children and adolescents with asthma, the
      accuracy of this dyspnea scale improves as the post-exercise percentage fall in
      FEV1 increases. However, the predictive value of the scale is suboptimal when the
      percentage fall in FEV1 is lower.

PMID- 21085818
TI  - Poor perception of dyspnea following methacholine challenge test in patients with
      asthma.
AB  - OBJECTIVE: To determine the proportion of asthma patients with a poor perception
      of dyspnea, correlating the level of that perception with the severity of acute
      bronchoconstriction, bronchial hyperresponsiveness, use of maintenance
      medication, and asthma control. METHODS: Uncontrolled clinical trial involving
      asthma patients treated at the Pulmonology Outpatient Clinic of the Sao Lucas
      Hospital, in Porto Alegre , Brazil. Methacholine challenge testing was performed
      using a five-breath dosimeter protocol. The perception of dyspnea after each
      breath was determined using the Borg scale. Data concerning asthma control,
      medication in use, and use of rescue short-acting bronchodilators were recorded.
      RESULTS: Of the 65 patients included in the study, 53 completed the evaluation.
      Of those, 32 (60.5%) showed adequate perception of dyspnea after the methacholine
      challenge test, whereas 21 (39.5%) did not perceive any changes in the degree of
      dyspnea even after a 20% fall in FEV1. There were no significant differences
      between the two groups regarding baseline FEV1, percentage fall in FEV1, and the
      dose of methacholine causing a 20% fall in FEV1. The perception of dyspnea was
      not significantly associated with age (p = 0.247); gender (p = 0.329); use of
      maintenance medication (p = 0.152); asthma control (p = 0.562), bronchial
      hyperresponsiveness (p = 0.082); or severity of acute bronchoconstriction (p =
      0.749). CONCLUSIONS: A significant proportion of asthma patients have a poor
      perception of dyspnea. The factors related to the inability of these patients to
      identify changes in pulmonary function have not yet been well defined. In order
      to reduce asthma-related morbidity and mortality, it is essential that this group
      of patients be identified and counseled.

PMID- 21085819
TI  - Adhesiveness and purulence of respiratory secretions: implications for
      mucociliary transport in patients with bronchiectasis.
AB  - OBJECTIVE: To analyze and compare the transport properties of respiratory
      secretions, classified by selected parameters, in individuals with bronchiectasis
      unrelated to cystic fibrosis. METHODS: We collected mucus samples from 35
      individuals with bronchiectasis unrelated to cystic fibrosis. The samples were
      first classified by their surface properties (adhesive or nonadhesive), as well
      as by their aspect (mucoid or purulent). We then tested the samples regarding
      relative transport velocity (RTV), displacement in a simulated cough machine
      (SCM), and contact angle (CA). For the proposed comparisons, we used ANOVA
      models, with a level of significance set at 5%. RESULTS: In comparison with
      nonadhesive samples, adhesive samples showed significantly less displacement in
      the SCM, as well as a significantly higher CA (6.52 +/- 1.88 cm vs. 8.93 +/- 2.81
      cm and 27.08 +/- 6.13o vs. 22.53 +/- 5.92o, respectively; p < 0.05 for both). The
      same was true in the comparison between purulent and mucoid samples (7.57 +/-
      0.22 cm vs. 9.04 +/- 2.48 cm and 25.61 +/- 6.12o vs. 21.71 +/- 5.89o; p < 0.05
      for both). There were no significant differences in RTV among the groups of
      samples, although the values were low regardless of the surface properties
      (adhesive: 0.81 +/- 0.20; nonadhesive: 0.68 +/- 0.24) or the aspect (purulent:
      0.74 +/- 0.22; mucoid: CONCLUSIONS: The respiratory secretions of patients with
      bronchiectasis showed decreased mucociliary transport. Increased adhesiveness and
      purulence cause the worsening of transport properties, as demonstrated by the
      lesser displacement in the SCM and the higher CA.

PMID- 21085820
TI  - Ventilation strategy and its influence on the functional performance of lung
      grafts in an experimental model of single lung transplantation using non-heart
      beating donors.
AB  - OBJECTIVE: To compare the influence of two different ventilation strategies
      volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV)-on
      the functional performance of lung grafts in a canine model of unilateral left
      lung transplantation using donor lungs harvested after three hours of
      normothermic cardiocirculatory arrest under mechanical ventilation. METHODS: The
      study comprised 40 mongrel dogs, randomized into two groups: VCV and PCV. Of the
      20 recipients, 5 did not survive the transplant, and 5 died before the end of the
      post-transplant assessment period. The remaining 10 survivors (5 in each group)
      were evaluated for 360 min after lung transplantation. The functional performance
      of the grafts was evaluated regarding respiratory mechanics, gas exchange, and
      lung graft histology. RESULTS: There were no significant differences between the
      groups regarding respiratory mechanics (peak inspiratory pressure, plateau
      pressure, mean airway pressure, dynamic compliance, and static compliance) or gas
      exchange variables (PaO2, venous oxygen tension, PaCO2, venous carbon dioxide
      tension, and the arterial-venous oxygen content difference). The
      histopathological findings were consistent with nonspecific acute lung injury and
      did not differ between the groups. CONCLUSIONS: This model of lung
      transplantation showed that the functional performance of lung grafts was not
      influenced by the ventilation strategy employed during the first six hours after
      reperfusion.

PMID- 21085821
TI  - Predictors of physical and mental health-related quality of life in patients with
      interstitial lung disease: a multifactorial analysis.
AB  - OBJECTIVE: To determine predictors of health-related quality of life (HRQoL) in
      patients with interstitial lung disease (ILD). METHODS: A cross-sectional study
      comprising 63 patients, all of whom underwent lung function testing and the six
      minute walk test. The following instruments were used: the Medical Outcomes Study
      36-item Shortform Survey (SF-36), the Saint George's Respiratory Questionnaire
      (SGRQ), the Beck Anxiety Inventory, the Beck Depression Inventory, and the
      Modified Medical Research Council Dyspnea Scale. Principal component analysis was
      used in order to reduce the dimensionality of the data, thereby identifying the
      predictor variables, and multiple linear regression analysis was used in order to
      identify the explanatory variables. RESULTS: Of the 63 patients, 34 were female.
      The mean age was 60.1 +/- 13.3 years, the mean FVC was 64.17 +/- 15.54% of
      predicted, and the mean DLCO was 44.21 +/- 14.47% of predicted. All of the
      patients evaluated had impaired HRQoL, scoring worst for the SF-36 physical
      functioning and SGRQ activity domains. Of the patients evaluated, 60.3% and 57.1%
      showed symptoms of anxiety and depression, respectively. The principal component
      analysis identified one predictor of physical HRQoL and one predictor of mental
      HRQoL. Depression had a strong influence on the predictor of mental HRQoL, and
      the degree of dyspnea had a strong influence on both predictors of HRQoL in the
      patients evaluated. Variables related to lung function, exercise capacity, and
      anxiety had no impact on these predictors. CONCLUSIONS: In our sample of patients
      with ILD, the degree of dyspnea had a major impact on the physical and mental
      HRQoL, and depression had an impact on mental HRQoL.

PMID- 21085822
TI  - Dyspnea in COPD: beyond the modified Medical Research Council scale.
AB  - OBJECTIVE: To determine the correlations among various dyspnea scales,
      spirometric data, exercise tolerance data, and the Body mass index, airway
      Obstruction, Dyspnea, and Exercise capacity (BODE) index in patients with COPD.
      METHODS: Between March of 2008 and July of 2009, 79 patients with COPD were
      recruited, and 50 of those patients were included in the study. After being
      regularly treated with formoterol for one month, the patients completed the
      modified Medical Research Council (mMRC, dyspnea scale), Baseline Dyspnea Index
      (BDI), Oxygen Cost Diagram (OCD), and Shortness Of Breath Questionnaire (SOBQ).
      Subsequently, the patients underwent spirometry and six-minute walk tests
      (6MWTs), with determination of the six-minute walk distance (6MWD), as well as
      initial and final SpO2. All patients also completed the Visual Analogue Scale
      (VAS) and the Borg scale. RESULTS: The best correlations were between the Borg
      scale and the VAS (r s = 0.79) and between the BDI and the SOBQ (r s = -0.73).
      Among the one-dimensional scales (the VAS, mMRC, OCD, and Borg scale), only the
      VAS correlated with the spirometric parameters, whereas the multidimensional
      scales BDI and SOBQ did correlate, but poorly. The MRC, BDI, and SOBQ correlated
      well with 6MWD. Among the spirometric data, inspiratory capacity (IC) and FVC had
      the strongest correlations with 6MWD. In the multivariate analysis, BDI and IC
      were selected as the best predictors of 6MWD. CONCLUSIONS: Multidimensional
      dyspnea scales should be applied in the evaluation of COPD patients.

PMID- 21085823
TI  - Lung alterations in a rat model of diabetes mellitus: effects of antioxidant
      therapy.
AB  - OBJECTIVE: To evaluate structural alterations of the lung in rats with diabetes
      mellitus (DM), by quantifying oxidative stress and DNA damage, as well as to
      determine the effects that exogenous superoxide dismutase (SOD) has on such
      alterations. METHODS: A controlled experimental study involving 40 male Wistar
      rats, divided into four groups (10 animals each): control; SOD-only (without DM
      but treated with SOD); IDM-only (with streptozotocininduced DM but untreated);
      and IDM+SOD (with streptozotocin-induced DM, treated with SOD). The animals were
      evaluated over a 60-day period, day 0 being defined as the day on which the
      streptozotocin-injected animals presented glycemia > 250 mg/dL. The SOD was
      administered for the last 7 days of that period. At the end of the study period,
      samples of lung tissue were collected for histopathological analysis, evaluation
      of tissue oxidative stress, and assessment of DNA damage. RESULTS: There were no
      significant differences among the groups regarding DNA damage. In the IDM-only
      group, there was a significant increase in the extracellular matrix and
      significantly greater hyperplasia of the capillary endothelium than in the SOD
      only and control groups. In addition, there were significant changes in type II
      pneumocytes and macrophages, suggesting an inflammatory process, in the IDM-only
      group. However, in the IDM+SOD group, there was a reduction in the extracellular
      matrix, as well as normalization of the capillary endothelium and of the type II
      pneumocytes. CONCLUSIONS: Exogenous SOD can reverse changes in the lungs of
      animals with induced DM.

PMID- 21085824
TI  - Evolution of performance status, body mass index, and six-minute walk distance in
      advanced lung cancer patients undergoing chemotherapy.
AB  - OBJECTIVE: To evaluate the effect of chemotherapy on the physical condition of
      patients with advanced lung cancer. METHODS: We evaluated 50 patients with non
      small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology
      Group (ECOG) performance status scale scores between zero and two. All patients
      underwent chemotherapy using paclitaxel and platinum derivatives and were
      evaluated at three time points (prechemotherapy, postchemotherapy and six months
      after starting the treatment), at which the ECOG scale, the body mass index (BMI)
      and the six-minute walk distance (6MWD) were assessed. RESULTS: Of the 50
      patients included in the study, 14 died, 5 were excluded due to the worsening of
      their performance status, and 31 completed the six-month follow-up. There was no
      statistically significant difference between the time points of assessment for
      BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six
      months later, p = 0.218) or for 6MWD. Performance status improved, and this was
      especially due to the increase in the number of asymptomatic patients after the
      six-month follow-up (p = 0.031). CONCLUSIONS: Chemotherapy had a beneficial
      effect on the performance status of the patients. No significant changes in BMI
      or 6MWD were found during the study period, which might suggest the maintenance
      of the physical condition of the patients.

PMID- 21085825
TI  - Reproducibility of the Brazilian Portuguese version of the European Organization
      for Research and Treatment of Cancer Core Quality of Life Questionnaire used in
      conjunction with its lung cancer-specific module.
AB  - OBJECTIVE: The assessment of the quality of life in patients with lung cancer has
      become one of the main goals in current clinical trials. To assess the quality of
      life of these patients, the most widely used instrument is the 30-item European
      Organization for Research and Treatment of Cancer Core Quality of Life
      Questionnaire (EORTC QLQ-C30) in conjunction with its supplemental 13-item lung
      cancer-specific module (QLQ-LC13). The objective of this study was to assess the
      reproducibility of the Brazilian Portuguese version of these questionnaires.
      METHODS: A prospective study involving 30 stable outpatients with lung cancer who
      completed the instruments on the first day of the study and two weeks later.
      RESULTS: The test-retest reproducibility using the intraclass correlation
      coefficient for the EORTC QLQ-C30 and the QLQ-LC13 ranged from 0.64 to 1.00 and
      from 0.64 to 0.95, respectively. No correlations were found between the domains
      of the instruments and clinical parameters. CONCLUSIONS: Our findings show that
      these instruments were reproducible in this sample of patients with lung cancer
      in Brazil.

PMID- 21085826
TI  - Factors that motivate smokers to seek outpatient smoking cessation treatment at a
      university general hospital.
AB  - OBJECTIVE: To describe the reasons smokers give for seeking smoking cessation
      treatment, correlating those reasons with sociodemographic characteristics,
      clinical data, stage of readiness to change, and severity of nicotine dependence.
      METHODS: Between February of 2008 and February of 2009, we evaluated 53 smokers
      who were naive to smoking cessation treatment and sought such treatment at the
      psychoactive substance abuse outpatient clinic of a university general hospital.
      The instruments used in the study were as follows: a form for the collection of
      sociodemographic and clinical data; the Fagerstrom Test for Nicotine Dependence;
      the University of Rhode Island Change Assessment scale; and a questionnaire on
      the smoking habit. RESULTS: The sample comprised 34 women and 19 men, with a mean
      age of 48.1 years. Most of the participants had less than 8 years of schooling,
      had tobacco-related diseases, started smoking during adolescence, had smoked for
      more than 20 years, and had high nicotine dependence. The decision to quit
      smoking was mainly influenced by advice from family members, and the decision to
      seek specialized smoking cessation treatment was influenced by physicians. Most
      of the men were in the contemplation stage of change, whereas the women tended to
      have a more balanced distribution of the stages (p = 0.007). The women had
      attempted to quit smoking more often than had the men (p = 0.017) and also had a
      higher level of nicotine dependence (p = 0.053). CONCLUSIONS: The findings of
      this study highlight the role of health professionals in the approach to smoking
      cessation and suggest the importance of interventions that are more targeted, in
      view of the differences between men and women.

PMID- 21085827
TI  - Comparison among three cold staining methods in the primary diagnosis of
      tuberculosis: a pilot study.
AB  - OBJECTIVE: In developing countries, sputum smear microscopy is the main tool for
      pulmonary tuberculosis case finding. The objective of the present study was to
      evaluate the diagnostic efficacy of Gabbett's staining (GS) and modified cold
      staining (MCS), both of which are two-step methods, in comparison with that of
      fluorescent staining (FS), which is a three-step method, for the detection of AFB
      in sputum smears. METHODS: Our sample comprised 260 sputum samples collected from
      individuals suspected of having pulmonary tuberculosis at Kasturba Hospital, in
      Manipal, India. Smears were prepared in triplicate: one each for FS, MCS, and GS.
      The smears were randomly numbered so that the examiner was blinded to the sample
      identities. RESULTS: Of the 260 samples, 16 (6.15%), 15 (5.77%), and 13 (5.00%)
      showed positive AFB results with FS, MCS, and GS, respectively. The sensitivity
      of GS and MCS, in comparison with that of FS, was 81.25% and 93.75%,
      respectively. The concordance of GS and MCS with FS was good (0.988 and 0.996,
      respectively), and no statistically significant differences were found.
      CONCLUSIONS: Although MCS and GS were found to be less sensitive than was FS,
      which is evaluated under fluorescence microscopy, the first two are promising
      methods for the diagnosis of tuberculosis.

PMID- 21085828
TI  - The revised tumor-node-metastasis staging system for lung cancer: changes and
      perspectives.
AB  - The tumor-node-metastasis (TNM) staging system for lung cancer has been modified
      since its first edition in the late 1960s. Its seventh edition has been recently
      published and, for the first time, a truly worldwide database was analyzed in
      order to propose modifications in the staging. Significant changes have been made
      in the tumor and metastasis descriptors. Although the recommendations for the
      node descriptor have remained unchanged, the analysis of the factors related to
      this descriptor suggests that modifications will be made in the future. The
      forthcoming revisions of the TNM staging system might take the molecular aspects
      of lung cancer into consideration, aiming at a more refined staging system.

PMID- 21085829
TI  - Tuberculosis and gender in a priority city in the state of Rio de Janeiro,
      Brazil.
AB  - The objective of this study was to compare gender differences among tuberculosis
      patients in a city with a high incidence of tuberculosis. This was a cross
      sectional questionnaire-based study involving 560 tuberculosis patients (373
      males and 187 females). Sociodemographic and clinical data, as well as data
      related to diagnostic criteria and treatment outcome, were collected (from the
      questionnaires and medical records) and subsequently compared between the
      genders. The median time from symptom onset to diagnosis was 90 days. There were
      no differences between the genders regarding the clinical presentation,
      diagnostic criteria, previous noncompliance with treatment, time from symptom
      onset, number of medical appointments prior to diagnosis, or treatment outcome.
      Gender-specific approaches are not a priority in Brazil. However, regardless of
      patient gender, the delay in diagnosis is a major concern.

PMID- 21085830
TI  - Antituberculosis drugs: drug interactions, adverse effects, and use in special
      situations. Part 1: first-line drugs.
AB  - The main objectives of tuberculosis therapy are to cure the patients and to
      minimize the possibility of transmission of the bacillus to healthy subjects.
      Adverse effects of antituberculosis drugs or drug interactions (among
      antituberculosis drugs or between antituberculosis drugs and other drugs) can
      make it necessary to modify or discontinue treatment. We briefly review the new
      guidelines for the pharmacological treatment of tuberculosis, introduced by the
      Brazilian National Ministry of Health in 2009, and describe the general mechanism
      of action, absorption, metabolization, and excretion of the first-line drugs used
      in the basic regimen. We describe adverse drug reactions and interactions (with
      other drugs, food, and antacids), as well as the most appropriate approach to
      special situations, such as pregnancy, breastfeeding, liver failure, and kidney
      failure. We also describe the mechanisms by which the interactions among the
      antituberculosis drugs used in the basic regimen can cause drug-induced
      hepatitis, and we discuss the alternatives in this situation.

PMID- 21085831
TI  - Antituberculosis drugs: drug interactions, adverse effects, and use in special
      situations. Part 2: second line drugs.
AB  - The main objectives of tuberculosis therapy are to cure the patients and to
      minimize the possibility of transmission of the bacillus to healthy subjects.
      Adverse effects of antituberculosis drugs or drug interactions (among
      antituberculosis drugs or between antituberculosis drugs and other drugs) can
      make it necessary to modify or discontinue treatment. We describe the general
      mechanism of action, absorption, metabolization, and excretion of the drugs used
      to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones,
      cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid).
      We describe adverse drug reactions and interactions (with other drugs, food, and
      antacids), as well as the most appropriate approach to special situations, such
      as pregnancy, breastfeeding, liver failure, and kidney failure.

PMID- 21085832
TI  - Lipoid pneumonia secondary to long-term use of evening primrose oil.
AB  - Lipoid pneumonia is an underdiagnosed disease that is caused by the aspiration of
      lipid particles into the lungs. Although most of the reported cases have been
      associated with the use of mineral oil as a laxative, other lipid substances can
      also cause the disease. We report the case of a 50-year-old female patient with a
      complaint of productive cough who was initially diagnosed with bronchial
      hyperresponsiveness and gastroesophageal reflux disease (GERD). The patient was
      treated for GERD. Because the productive cough persisted, the patient underwent
      chest CT, fiberoptic bronchoscopy, and open lung biopsy. She was diagnosed with
      lipoid pneumonia. The patient was questioned regarding the use of lipid
      substances, and she reported the chronic use of evening primrose oil. After the
      discontinuation of the substance and the maintenance of GERD treatment, her
      condition improved.

PMID- 21085833
TI  - Recurrent pulmonary hyalinizing granuloma.
AB  - We report the case of a 61-year-old male patient who underwent surgical excision
      of a lung mass for anatomopathological study. The patient had previously
      presented with fever, dry cough, and chest pain, together with lung masses
      detected by chest X-ray, and had undergone thoracotomy for diagnostic
      investigation on two occasions (1976 and 1981), although a conclusive diagnosis
      had not been made. A CT scan of the chest revealed large masses with areas of
      calcification in both lung fields. The anatomopathological study was consistent
      with pulmonary hyalinizing granuloma. In the postoperative period, the patient
      experienced several episodes of bronchospasm, which was reversible with the use
      of symptomatic medication. At this writing, the patient was receiving maintenance
      therapy with prednisone (40 mg/day) and had shown clinical improvement.

PMID- 21085834
TI  - Paracoccidioidomycosis and cancer.

PMID- 21085835
TI  - New reference values for maximal respiratory pressures in the Brazilian
      population: corrections.

PMID- 21085838
TI  - [New oncologic paradigm in head and neck surgery].

PMID- 21085839
TI  - [Epithelioid sarcoma: clinical behavior, prognostic factors and survival].
AB  - OBJECTIVE: To relate the clinical characteristics and evaluations of patients
      with epithelioid sarcomas. METHODS: Careful analysis of 25 epithelioid sarcoma
      cases registered in Instituto Nacional do Cancer between june 1987 and july 2005.
      RESULTS: Mean age at diagnosis was 33 years old, ranged from 10 to 70. The
      primary site of presentation was the upper extremity in twelve patients (48%).
      The size of the tumor was given in 19 cases, with the mean size of 5 cm, while
      they ranged from 1.5 to 15 cm. Surgery was made in 17 patients, with eleven
      amputation. Tumors margins were free in fifteen patients, positive in three and
      in seven were not studied. Six received any type of chemotherapy and 14 received
      treatment with radiotherapy with mean dose of 46,5 Gy. Local recurrence occurred
      in thirteen cases (52%). Nodal spread was diagnosed in nine (36%). Pulmonary
      metastases were diagnosed in seven patients (28%). Six patients underwent cancer
      treatment in its entirety at the National Institute of Cancer. At present twelve
      patients are alive without disease, two have disease and eleven patients have
      died. CONCLUSION: Epithelioid sarcoma is a rare subset of soft tissue sarcoma
      with high rate of local recurrence, regional node and distant metastases. Occurs
      predominantly in young patients, mainly on the superior member extremities.
      Surgical treatment of epithelioid sarcoma consists of early wide local resection
      to negative microscopic margins. These patients require carefully follow-up to
      evaluate local recurrence, nodal metastases, and pulmonary metastases.

PMID- 21085840
TI  - [Frequency of vomiting after emergency abdominal surgery in a reference public
      hospital].
AB  - OBJECTIVE: The objective of this study was to evaluate the frequency of the
      vomiting after urgency abdominal surgery in the Alagoas reference public
      hospital. METHODS: After approved in the Ethic and Search Committee of the
      Alagoas Federal University, the information was got in the medical records 24
      hours after urgency abdominal surgery. Fisher test and chi-square with Yates
      correction were used do compare proportions assuming a 5% significance level. Was
      calculated 95% confidence interval to proportions when was possible. RESULTS:
      Were 100 patients, 85% men (85/100, CI 95% 0.78-0.92). The vomiting frequency was
      25% without statistical difference between abdominal surgery after trauma and
      inflammatory acute abdomen (P=0.46). There was not statistical difference between
      anesthetic techniques (P=0.99). CONCLUSION: The general vomiting prevalence after
      the urgency abdominal surgery in the Alagoas reference public hospital was 25%.

PMID- 21085841
TI  - [Mesenteric cyst--clinical and pathological aspects].
AB  - OBJECTIVE: To evaluate epidemiologic, clinical, pathologic and therapeutic
      characteristics of the mesenteric cysts in hospitals of Sergipe, Brazil. METHODS:
      Mesenteric cysts were assessed by a non-interventional cross-sectional study from
      the archives of the Pathology Laboratory of Federal University of Sergipe between
      1995 and 2007. The charts of the patients were reviewed in order to find out:
      gender, age, clinical findings, complementary exams and therapeutic approach.
      RESULTS: Eighteen cases of mesenteric cysts were found. Females were more
      affected (72.2%). Mean of age of the patients was 30.46. More frequent symptoms
      were pain and abdominal mass. Ultrasonography of abdomen, performed in all
      patients, was not conclusive in half of the cases. CTscan of abdomen with
      contrast was performed in six cases, being cystic tumor well identified in all of
      them. Regarding histopathology, 6 lymphangiomas, 8 mesotheliomas, 1 hemorrhagic
      cyst in organization and 1 mucinous cyst were found. Surgical treatment was
      performed in all cases. Intracystic bleeding was the main complication in 3
      cases. CONCLUSION: The mesenteric cysts presented clinically with unspecific
      symptoms. CTscan was more effective than ultrasonography for the diagnosis.
      Lymphangiomas and mesothelioma had been found in equal ratios. The complete
      resection of the cyst was the treatment of election. There were no deaths in
      postoperative period.

PMID- 21085842
TI  - [Anal cancer and sexually transmitted diseases: what is the correlation?].
AB  - OBJECTIVE: Anal cancer is a rare tumor, which incidence is influenced by sexual
      behavior. The purpose of this paper is to verify the correlation between anal
      cancer and sexually transmitted diseases, such as HPV, HIV, Gonococci infection,
      Chlamydia infection, syphilis and others. METHODS: All the internments due to
      anal cancer, HIV, HPV, syphilis, Gonococci infection, Chlamydia infection and
      other sexually transmitted diseases in public healthy in Brazil were collected at
      Datasus site between 1998 and 2007. The Pearson correlation test was done.
      RESULTS: There was a high correlation between anal cancer and HPV admissions
      (r=0.98, p<0.001). There was negative correlation between anal cancer and
      Gonococci infection admissions (r=-0.81, p=0.005) and anal cancer and Chlamydia
      infection (r=-0.74, p=0.014). There was not statistic significant correlation
      between anal cancer and HIV admissions (r=0.40, p=0.245), between anal cancer and
      other sexually transmitted diseases (r=0.55, p=0.1), and between anal cancer and
      syphilis (r=-0.61, p=0.059). CONCLUSION: There was a high positive correlation
      between anal cancer and HPV admissions in Brazil. There were negative
      correlations between anal cancer and Gonococci infection and between anal cancer
      and Chlamydia infection admissions.

PMID- 21085843
TI  - [Analysis of complications in metastatic prostate cancer patients submitted to
      bilateral orchiectomy].
AB  - OBJECTIVE: To analyze the possible complications that the surgical hormonal
      ablation can cause to the submitted patients. METHODS: That's an analytical
      transversal study with a sample of 25 patients, between 58 to 82 years, carriers
      of metastatic prostate cancer, submitted to the bilateral orchiectomy in the
      Professor Alberto Antunes University Hospital 's (HUPAA-UFAL), in the period of
      January of 2003 to December of 2008. It was made an evaluation by an objective
      questionnaire for those who were still alive. RESULTS: Of the 25 evaluated
      patients, 56% were still alive, with average of current age of 71 years, having
      presented as more frequent complications: reduction of the libido and sexual
      impotence (100%), bone fragility (64%), problems of memory and variations of mood
      (57%), hot waves and gain of weight (50%). 86% of the interviewed ones had
      related to be satisfied with the results of the procedure and had affirmed that
      they can have a normal daily life, with significant improvement of the clinical
      stage. About the adjuvant treatments, only 36% had carried through, being most
      common, chemotherapy (36%) and x-ray (29%). CONCLUSION: The bilateral orchiectomy
      constitutes in a good alternative for metastatic prostate cancer patients, in a
      way that it is observed satisfaction of the majority of the patients in relation
      to the improvement of the symptoms and the presented complications had not great
      impact in the daily life of the same ones.

PMID- 21085845
TI  - [Expensive therapy of vascular trauma].
AB  - OBJECTIVE: To analyze all expenses paid to the first surgical approached for
      vascular lesion patients admitted at Hospital Joao XXIII/FHEMIG, between years
      2004 until 2006. METHOD: It is about an ethical approved study, retrospective and
      descriptive from audit over 70 eligible patients enrolled by Cardiovascular
      Service. RESULTS: Five (7.14%) patient's files were excluded for bad quality
      records. The costs were R$ 103,614.96 (US$ 60,949.97) and R$ 185,888.21 (US$
      109,346.0), a 44% sliding scale for endowment from Brazilian Public System and
      private medical assistance estimate, respectively. Indeed, the data showed direct
      relationship between costs and anatomic topographic and exponential increased
      expenses when blood and/or vascular prosthesis were utilized. CONCLUSION: Audit
      in health system is a must to making decision and evidences the expensive therapy
      for vascular lesions.

PMID- 21085844
TI  - [Is it possible to predict the length of knee flexor tendons by anthropometry?].
AB  - OBJECTIVE: To compare the anthropometric data and the sportive way of life with
      the hamstring tendons dimensions, prospectively, in order to create a rule to
      predetermine its dimensions. METHODS: General and anthropometric data were
      collected from 30 patients that were submitted to anterior cruciate ligament
      reconstruction. These data were correlated to the diameter and length of the
      hamstring tendons. The data collected were: height, weight, age, knee lesion
      side, body mass, sportive training level, femoral length, tibia length, thigh
      circumference, and knee circumference. The correlation was made by Pearson
      coefficient. RESULTS: Statistic significant correlation occurred only with height
      and tibia length versus the gracilis and semitendinous tendon length. Using
      linear regression the relations found could be expressed with the following
      formulas: semitendinous length = -2.276 + 0.177 x height; semitendinous length =
      13.048 + 0.46 x tibia height; gracilis length = -9.413 + 0.207 x height; gracilis
      length = 7.036 + 0.583 x tibia height. CONCLUSION: It is possible to predetermine
      hamstring tendons length through linear regression formulas before surgical
      intervention.

PMID- 21085846
TI  - [Intestinal lengthening using a gastric graft: experimental study in pigs].
AB  - OBJECTIVE: Novel experimental technique of intestinal lengthening with a gastric
      graft in swines is proposed. METHODS: Four male large white swines, weighing 15
      to 20 kg and aging 50 to 60 days were underwent an intestinal lengthening using a
      gastric graft (Figure 1). Swines were re-operated to check the aspect of the
      lengthening surgery. At this time intestinal fragments of suture lines,
      respecting a 5 cm margin, were removed and sent to histological analysis.
      RESULTS: There wasn't any graft ischemia or necrosis, residual stomach was
      already dilated by the time of relaparotomies, regaining 50% of its original
      size. Only an intense atrophy of the gastric graft mucosa with no signs of
      necrosis at histological study (Figure 2). CONCLUSION: Lengthening using a
      gastric graft is technically feasible, with viability of the graft. Studies with
      swines with SBS in a larger cohort will be necessary to analyze stomach graft
      function. In the future, this technique can be a bridge to intestinal
      transplantation.

PMID- 21085847
TI  - [Effects of gadolinium chloride on sodium taurocholate-induced pancreatitis in
      rats].
AB  - OBJECTIVE: To evaluate the effects of the use of gadolinium chloride before and
      after induction of acute pancreatitis with sodium taurocholate 3% in rats.
      METHODS: Wistar rats were divided into five groups: SF--control with saline intra
      ductal and IV; GD control with saline intra-ductal and gadolinium chloride IV; TS
      -with AP control induced by sodium taurocholate 3% and saline IV; GDTS--pre
      treatment with GD (24 hours before the induction of AP) and TSGD--treatment with
      GD (1 hour after the induction of AP). Analysis was made in serum amylase,
      transaminases and TNF-alpha; determination of the MPO activity in lung tissue,
      lung and pancreatic histology. RESULTS: The number of dead animals before the end
      of the experiment was significantly higher in TSGD (P = 0.046). The scores of
      pancreatitis and lung damage were higher in the groups that used sodium
      taurocholate compared to groups with intra-ductal infusion of saline solution.
      There were no differences in other variables studied when comparing TS, GDTS and
      TSGD groups. CONCLUSION: The benefits with the use of gadolinium chloride as a
      prophylactic and therapeutic drug were not demonstrated.

PMID- 21085848
TI  - [Low intensity laser therapy effects on cell proliferation and differentiation:
      review of the literature].
AB  - Low energy laser has been used as an adjuvant therapy or as a therapeutic tool in
      many different areas of Dentistry. It is recognized by its anti-inflammatory and
      analgesic properties, and also as a tissue repair inductor. Low intensity laser
      property in stimulate cell proliferation during wound healing and its
      biomodulation mechanisms are discussed in this paper. These properties have
      already been established for cultured benign cells, but there is a controversy
      when extended to the spectrum of the malignant neoplastic process, normally
      generating great discussions. The objective of this work was to perform a
      literature review about the low intensity laser capacity in induce cell
      proliferation. The discussion is specially concerned about its effects on
      malignant cells.

PMID- 21085849
TI  - [Cutaneous surgery workshop].
AB  - The training of physician request knowledge, skills and attitudes for the
      effective exercise of professional practice. The training of basic surgical
      techniques, used in outpatient procedures, will prepare students to work in
      different scenarios. This work presents a proposal for teaching through workshops
      for cutaneous surgery in an experimental model.

PMID- 21085850
TI  - [Commitments of medicine: reflections on the prayer of Maimonides].
AB  - Science/art millennial, medicine involves, by its nature, a strong commitment to
      basic principles of bioethics that are summarized in the pursuit of health and
      welfare of people and communities in their broadest sense. Such commitments may
      be more formal, such as obedience to the Codes of Ethics and Ethics; public, such
      as oaths, or consciousness, which are the prayers. The latter model is the Prayer
      of Maimonides, presented in this article.

PMID- 21085851
TI  - [The pleural wrap in the thoracic esophageal perforation].
AB  - The thoracic esophageal perforations frequently complicate with fistula when
      submitted to primary suture. The use of autogenous tissues, like pleura, to
      reinforce the primary suture has proved to be useful in reduce the incidence of
      fistulas or at least the severity of the leaks in case they occur. The mortality
      has reduced too, consequently. A case of an extensive esophageal perforation is
      presented, where the use of pleural wrap to reinforce the esophagography was very
      important to contain the leak and to permit a good evolution of the patient.

PMID- 21085852
TI  - [Primary hyperaldosteronism. Report of two cases].
AB  - The authors present two cases of primary hyperaldosteronism, caused by
      functioning adenoma of the adrenal's cortex. The two females patients presented
      classic symptoms of the Conn's disease, especially hypokalemia and hypertension.
      Both were operated and unilateral adrenalectomy was done, with excellent outcome
      in one and satisfactory in the other one. It is discussed many aspects related to
      the incidence, the problems with the diagnosis, indication and surgery treatment.

PMID- 21085853
TI  - [Centenary of the discovery of Chagas disease: challenges and prospects].

PMID- 21085854
TI  - Injuries and envenoming by aquatic animals in fishermen of Coxim and Corumba
      municipalities, state of Mato Grosso do Sul, Brazil: identification of the
      causative agents, clinical aspects and first aid measures.
AB  - INTRODUCTION: The fishes of continental Brazil have socioeconomic importance due
      to their potential for sport fishing and commercial and subsistence uses, as seen
      in the Upper Paraguay River Basin, particularly in the municipalities of the
      Pantanal region, where it is the second largest economic activity. Injuries
      caused in professional fishermen are common and poorly studied, as in other
      regions of the country. METHODS: Data were obtained from questionnaires and
      interviews with 100 professional fishermen, 50 in each municipality, between
      December 2008 and October 2009. RESULTS: All the fishermen reported some kind of
      injury caused by fish stings (78% of injuries) and fish, alligator and snake
      bites (22%) on the hands (46% of cases) and feet (35% of cases). Most of the
      patients had mild symptoms. The most severe cases were associated with secondary
      bacterial infections and required specific treatment and prolonged recovery
      associated with social and economic losses. CONCLUSIONS: The results of this
      study indicate that the stressful work conditions, inattention to basic
      preventive measures and carelessness were factors that contributed to accidents
      and that the toxicity and ability to inflict mechanical trauma of some aquatic
      species, plus the ineffective use of first aid and hospital treatment,
      contributed to the high morbidity and complications in many cases. Data from this
      study are relevant to the fishing communities of the Pantanal region, since they
      reveal high rates of accidents, lack of knowledge concerning first aid, initial
      treatment, injury prevention and lack of medical follow-up of the population.

PMID- 21085855
TI  - Sand fly captures with Disney traps in area of occurrence of Leishmania
      (Leishmania) amazonensis in the state of Mato Grosso do Sul, mid-western Brazil.
AB  - INTRODUCTION: The work was conducted to study phlebotomine fauna (Diptera:
      Psychodidae) and aspects of American cutaneous leishmaniasis transmission in a
      forested area where Leishmania (Leishmania) amazonensis occurs, situated in the
      municipality of Bela Vista, State of Mato Grosso do Sul, Brazil. METHODS: The
      captures were conducted with modified Disney traps, using hamster (Mesocricetus
      auratus) as bait, from May 2004 to January 2006. RESULTS: Ten species of
      phlebotomine sandflies were captured: Brumptomyia avellari, Brumptomyia brumpti,
      Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia
      longipalpis, Psathyromyia campograndensis, Psathyromyia punctigeniculata,
      Psathyromyia shannoni and Sciopemyia sordellii. The two predominant species were
      Ev bourrouli (57.3%) and Bi flaviscutellata (41.4%), present at all sampling
      sites. Two of the 36 hamsters used as bait presented natural infection with
      Leishmania. The parasite was identified as Leishmania (Leishmania) amazonensis.
      CONCLUSIONS: Analysis of the results revealed the efficiency of Disney traps for
      capturing Bichromomyia flaviscutellata and the simultaneous presence of both
      vector and the Leishmania species transmitted by the same can be considered a
      predictive factor of the occurrence of leishmaniasis outbreaks for the human
      population that occupies the location.

PMID- 21085856
TI  - Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure.
AB  - INTRODUCTION: The purpose of this study was to determine digoxin serum
      concentrations in patients with Chagas' cardiomyopathy with chronic heart
      failure, because little is known concerning this laboratory test in patients with
      this condition. METHODS: This study focuses on 29 (29%) out of 101 patients with
      chronic heart failure secondary to Chagas' cardiomyopathy receiving digoxin
      therapy. Digoxin was measured by the immune-enzymatic method. RESULTS: New York
      Heart Association Functional Class III/IV was noted in 13 (45%) patients. The
      mean potassium serum level was 4.3 +/- 0.5 mEq/L, mean creatinine serum levels
      1.4+/- 0.3dg/100ml, and left ventricular ejection fraction 34.7 +/- 13.8%. The
      median digoxin serum level was 1.27 (0.55; 1.79)ng/ml. Sixteen (55%) patients had
      digoxin serum levels higher than 1.0 ng/ml. Abnormal digoxin serum levels were
      verified in 13 (45%) patients. Digoxin serum levels correlated moderately with
      creatinine serum levels (r = 0.39; p < 0.03) and negatively with sodium serum
      levels (r= -0.38; p= 0.03). CONCLUSIONS: Digoxin serum concentration should be
      measured in patients with Chagas' cardiomyopathy with chronic heart failure
      receiving digoxin therapy due to the potential for digoxin toxicity.

PMID- 21085857
TI  - Prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infection in men
      attending STD clinics in Brazil.
AB  - INTRODUCTION: The study aimed to assess the prevalence of Neisseria gonorrhoeae
      and Chlamydia trachomatis infections and identify demographic, behavioral and
      clinical factors correlated with such infections in men attending six sexually
      transmitted disease clinics in Brazil. METHODS: Multicentric, cross-sectional
      study performed among men attending STD clinics in Brazil. The study included STD
      clinics in six cities distributed throughout the five geographic regions of
      Brazil in 2005. Patients provided 20 ml of first catch urine for testing for NG
      and CT by DNA-PCR. RESULTS: A total of 767 (92.9%) men were included in the
      study. The mean age was 26.5 (SD 8.3) years-old. Prevalence of Chlamydia
      infection was 13.1% (95%CI 10.7%-15.5%) and gonorrhea was 18.4% (95%CI 15.7%
      21.1%). Coinfection prevalence was 4.4% (95%CI 2.95%-5.85%) in men who sought
      attendance in STI clinics. Factors identified as associated with C. trachomatis
      were younger age (15-24) [OR=1.4 (95%CI 1.01-1.91)], present urethral discharge
      [OR=4.8 (95%CI 1.52-15.05)], genital warts [OR=3.0 (95%CI 1.49-5.92)] and
      previous history of urethral discharge [OR=2.4 (95%CI 1.11-5.18)]. Variables
      associated with gonorrhea were younger age (15 to 24) [OR=1.5 (95%CI 1.09-2.05)],
      presence of urethral discharge [OR=9.9 (95%CI 5.53-17.79)], genital warts
      [OR=18.3 (95%CI 8.03-41.60)] and ulcer present upon clinical examination [OR=4.9
      (95%CI 1.06-22.73)]. CONCLUSIONS: These findings have important implications for
      education and prevention actions directed toward men at risk of HIV/STD. A venue
      based approach to offer routine screening for young men in STD clinics should be
      stimulated.

PMID- 21085858
TI  - Capillaria hepatica-induced septal fibrosis in rats: a contribution to the study
      of liver fibrogenesis.
AB  - INTRODUCTION: Septal fibrosis of the liver regularly develops in rats infected
      with the nematode Capillaria hepatica. Curative treatment of the infection
      prevents the development of septal fibrosis when intervention occurs up to
      postinfection day (PID) 15, but not later. The present investigation aimed to
      demonstrate which parasitic factors are present when the process of septal
      fibrosis can no longer be prevented by curative treatment. METHODS: Wistar rats
      were infected with 600 embryonated eggs of C. hepatica administered by gavage and
      treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17
      or 20. Rats from each group and their nontreated controls, were killed and
      examined 40 days after the end of treatment. RESULTS: Findings by PID 15 were
      compatible with the stage of complete maturation of infection, when worms and
      eggs were fully developed and a complex host-parasite multifocal
      necroinflammatory reaction showed greater intensity, but with no signs of septal
      fibrosis, which appeared from PID 17 onward. CONCLUSIONS: Since the worms
      spontaneously died by PID 15, not only septal fibrosis production, but also its
      maintenance and further development appeared dependent on the presence of eggs,
      which were the only parasitic factor remaining thereafter.

PMID- 21085859
TI  - Concurrent Dengue and malaria in the Amazon region.
AB  - INTRODUCTION: The Amazon region has extensive forested areas and natural
      ecosystems, providing favorable conditions for the existence of innumerous
      arboviruses. Over 200 arboviruses have been isolated in Brazil and about 40 are
      associated with human disease. Four out of 40 are considered to be of public
      health importance in Brazil: Dengue viruses (1-4), Oropouche, Mayaro and Yellow
      Fever. Along with these viruses, about 98% of the malaria cases are restricted to
      the Legal Amazon region. METHODS: This study aimed to investigate the presence of
      arboviruses in 111 clinical serum samples from patients living in Novo
      Repartimento (Para), Placido de Castro (Acre), Porto Velho (Rondonia) and
      Oiapoque (Amapa). The viral RNA was extracted and RT-PCR was performed followed
      by a Multiplex-Nested-PCR, using Flavivirus, Alphavirus and Orthobunyavirus
      generic and species-specific primers. RESULTS: Dengue virus serotype 2 was
      detected in two patients living in Novo Repartimento (Para) that also presented
      active Plasmodium vivax infection. CONCLUSIONS: Despite scant data, this
      situation is likely to occur more frequently than detected in the Amazon region.
      Finally, it is important to remember that both diseases have similar clinical
      findings, thus the diagnosis could be made concomitantly for dengue and malaria
      in patients living or returning from areas where both diseases are endemic or
      during dengue outbreaks.

PMID- 21085860
TI  - Seroprevalence of hepatitis B virus infection and associated factors among prison
      inmates in state of Mato Grosso do Sul, Brazil.
AB  - INTRODUCTION: This study aimed to estimate the prevalence of HBV infection and
      associated factors among prison inmates in Campo Grande, MS. METHODS: A total of
      408 individuals were interviewed regarding sociodemographic characteristics,
      associated factors and HBV vaccination using a standardized questionnaire. Blood
      samples were collected from all participants and serological markers for HBV were
      detected by enzyme-linked immunosorbent assay. Hepatitis B surface antigen
      (HBsAg) and/or antibodies against hepatitis B core antigen (anti-HBc) positive
      samples were tested for HBV-DNA by polymerase chain reaction. RESULTS: The
      overall prevalence of HBV infection was 17.9% (95%CI: 14.4-22.0). The HBsAg
      carrier rate was 0.5%; 56 (13.7%) individuals had been infected and developed
      natural immunity and 15 (3.7%) were positive for anti-HBc only. Ninety eight
      (24%) prisoners had only anti-HBs, suggesting that they had low vaccine coverage.
      An occult HBV infection rate of 0% was verified among anti-HBc-positive
      individuals. Multivariate analysis of associated factors showed that age > 35
      years-old, low schooling level and illicit drug use are significantly associated
      with HBV infection. CONCLUSIONS: Analysis of the data showed HBV infection
      prevalence similar or slightly lower than that reported in other of Brazilian
      prisons. Independent predictors of HBV infection in this population include older
      age, low schooling level and illicit drug use.

PMID- 21085861
TI  - Effects of flooding of the River Parana on the temporal activity of Anopheles
      (Nyssorhynchus) darlingi Root (Diptera: Culicidae), at the border state of Mato
      Grosso do Sul and Sao Paulo, Brazil.
AB  - INTRODUCTION: Study of the temporal activity of malaria vectors during the
      implantation of a hydroelectric power station on the River Parana, intended to
      generate electrical energy. The river separates the States of Sao Paulo and Mato
      Grosso do Sul, in Brazil. The objective was to verify whether alterations
      occurred in the wealth and diversity indices of Anopheles, following two
      successive floods, extended to the temporal activity and nycthemeral rhythm
      followed over a five year period. METHODS: Mosquito capture was performed monthly
      using the Human Attraction Technique and Shannon Traps. The first, executed for
      24h, provided the nycthemeral rhythm and the second, lasting 15 h, permitted the
      tracking of Anopheles during the two floods. RESULTS: The bimodal pattern of
      Anopheles darlingi defined before these floods was modified throughout the
      environment interventions. The same effect had repercussions on the populations
      of An albitarsis s.l., An triannulatus and An galvaoi. Activity prior to twilight
      was less affected by the environment alterations. CONCLUSIONS: The dam
      construction provoked changes in Anopheles temporal activity patterns, permitting
      classification of the area as an ecologically steady and unstable situation.
      Differences observed in Anopheles behavior due to the capture methods revealed
      the influence of solo and multiple attractiveness inside the populations studied.

PMID- 21085863
TI  - High molecular mass fraction in clinical isolates of Paracoccidioides
      brasiliensis.
AB  - INTRODUCTION: Different serum levels of the IgG/IgE for Paracoccidioides
      brasiliensis high mass molecular (hMM) fraction (~366 kDa) in the acute and
      chronic forms of the disease have been reported. Considering the nonexistence of
      hMM fraction investigation involving clinical isolates of P. brasiliensis, the
      present study aimed to investigate the presence of the hMM fraction (~366 kDa) in
      cell free antigens (CFA) from P. brasiliensis clinical isolates. METHODS: CFA
      from 10 clinical isolates and a reference strain (Pb18) were submitted to SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) followed by gel image capturing and
      densitometer analysis. Additionally, CFA from 20 isolates and Pb18 were analyzed
      by capture ELISA (cELISA) using polyclonal (polAb) or monoclonal (mAb) antibodies
      to the hMM fraction. RESULTS: The presence of the hMM component was observed in
      CFA of all samples analyzed by SDS-PAGE/densitometry and by cELISA. In addition,
      Pearson's correlation test demonstrated stronger coefficients between hMM
      fraction levels using pAb and mAb (R = 0.853) in cELISA. CONCLUSIONS: The soluble
      hMM fraction was present in all the P. brasiliensis clinical isolates analyzed
      and the reference strain Pb18, which could be used as a source of this antigen.
      The work also introduces for first time, the cELISA method for P. brasiliensis
      hMM fraction detection. Analysis also suggests that detection is viable using
      polAb or mAb and this methodology may be useful for future investigation of the
      soluble hMM fraction (~366 kDa) in sera from PCM patients.

PMID- 21085862
TI  - Sporothrix schenckii associated with armadillo hunting in Southern Brazil:
      epidemiological and antifungal susceptibility profiles.
AB  - INTRODUCTION: Sporotrichosis is the most common subcutaneous mycosis observed in
      Brazil and it is generally consequent to a little trauma caused by vegetal
      particles or spines which inoculate the fungi in the subcutaneous area. Although
      sporotrichosis had been frequently mentioned with armadillo hunting this form has
      not been widely reported in Brazil until now. In this study we report ten cases
      of sporotrichosis evolving the armadillo's hunting diagnosed in some towns
      located in the central and west regions of Rio Grande do Sul State. METHODS: The
      cases were established based on clinical and classic mycological laboratorial
      techniques. The susceptibility tests were conducted by microdilution technique
      according to M38-A2 CLSI documents. RESULTS: Ten cases of sporotrichosis
      associated with armadillo hunting detected in the State of Rio Grande do Sul were
      diagnosed by mycological methods. The susceptibility tests of Sporothrix
      schenckii isolates to antifungal agents itraconazole, ketoconazole and
      terbinafine showed that all the isolates were susceptible. CONCLUSIONS: The paper
      discusses some cultural aspects related to hunting of this wild animal as well as
      possible causes of this unexpected occurrence in southern Brazil.

PMID- 21085864
TI  - Immunohistochemical expression of oestrogen and progesterone receptors during
      experimental acute and chronic murine Schistosomiasis mansoni.
AB  - INTRODUCTION: The responsibility of Schistosoma mansoni in female infertility is
      still controversial. This study was conducted to evaluate the effect of acute and
      chronic schistosomiasis mansoni infection on the endometrium using
      immunohistochemical analysis of uterine hormone receptor expression. METHODS:
      Twenty-four nonpregnant swiss albino mice were divided into three groups:
      control, noninfected; acute; and chronic Schistosoma mansoni infection.
      Histological sections of uterine specimens were examined by light microscope with
      an image analyzing system to detect structural histological, estrogen receptor
      (ER) and progesterone receptor (PR) expression in the endometrium. RESULTS: No
      secretory phase was detected in the endometrium in acute and chronic Schistosoma
      infection. Hormone receptor expression (ER and PR) showed statistically
      significant differences among the groups (p< 0.05), with significant low ER
      hormone expression in chronic infection, compared to control proliferative,
      control secretory and acute infection cases, and statistically significant high
      PR expression in both acute and chronic infection cases compared to the control
      secretory cases (p< 0.05). CONCLUSIONS: Schistosomiasis mansoni seems to have an
      important impact on the hormone expression of affected women. Further studies to
      explore the mechanism of such changes are recommended.

PMID- 21085865
TI  - [Spatial analysis of tuberculosis/HIV coinfection: its relation with
      socioeconomic levels in a city in south-eastern Brazil].
AB  - INTRODUCTION: Spatial analysis of the distribution of tuberculosis/HIV
      coinfection was performed and associated with socioeconomic indicators in Sao
      Jose do Rio Preto, from 1998 to 2006. METHODS: New TB/HIV coinfection cases were
      georeferenced and incidence coefficients were calculated for spatial units.
      Moran's index was used to evaluate spatial associations of incidences. Multiple
      regressions selected variables that could best explain the spatial association of
      incidences. The local indicator of spatial association was used to identify
      significant spatial groupings. RESULTS: Moran's index was 0.0635 (p=0.0000)
      indicating that the incidence association occurred. The variable that best
      explained the spatial association of incidence was the percentage of heads of
      families with up to three years of education. The LISA cluster map for TB/HIV
      coinfection incidence coefficients showed groups with high incidence rates in the
      North and low incidence in the South and West regions of the municipality.
      CONCLUSIONS: The study elucidated the spatial geographic distribution of TB/HIV
      coinfection and determined its association with socioeconomic variables, thus
      providing data for oriented planning, prioritizing socially disadvantaged regions
      that present a higher incidence of the disease.

PMID- 21085866
TI  - [AIDS and transmissible opportunistic diseases in the Brazilian border area].
AB  - INTRODUCTION: Person-to-person transmission of HIV and other communicable
      diseases may be associated with human geographic mobility. This article evaluated
      the incidence of transmissible opportunistic diseases among AIDS cases that had
      been reported by municipalities in the Brazilian border area. METHODS: Brazilian
      border area municipalities were grouped into three cultural regions; the source
      data was AIDS cases registered with the Ministry of Health from 1990 to 2003,
      which were classified according to CDC-adapted, Rio de Janeiro/Caracas and death
      criteria; detected communicable opportunistic diseases were categorized into
      groups according to transmission: 1) inhalation agent; 2) contaminated water
      and/or food ingestion, and 3) interpersonal contact. The descriptive evaluation
      considered cultural region, years of schooling, sex and age group. RESULTS:
      Different AIDS incidence patterns were observed among groups of opportunistic
      diseases in each cultural region. The extreme southern region showed the greatest
      incidence of AIDS; the absolute incidence of female cases was greatest in the
      category of heterosexual transmission; the number of male cases was greatest
      among intravenous drug users; transmission was most frequent in the interpersonal
      contact group, particularly incidences of candidiasis; tuberculoses and
      pneumonias were most frequent in the inhalation agent transmission group; the
      contaminated water/food ingestion transmission group showed an unchanged pattern
      of absolute incidence. CONCLUSIONS: The Brazilian border area is a very important
      and heterogeneous geographic phenomenon; AIDS programs must recognize different
      cultural geographies.

PMID- 21085867
TI  - [Rotavirus prevalence in infants and children in the public healthcare system of
      the state of Pernambuco].
AB  - INTRODUCTION: Rotaviruses are considered important etiological agents of acute
      gastroenteritis and a common cause of the hospitalization of children aged zero
      to four years-old. In Brazil, the incidence of rotavirus gastroenteritis in
      children is 12 to 42% and the distribution of infection is related to
      seasonality, which apparently occurs in different periods and intensity according
      to each region. The study investigated group A rotavirus in fecal samples of
      suspected children attended by the public health system of the State of
      Pernambuco. METHODS: Diagnosis was achieved by ELISA and the Latex agglutination
      test. RESULTS: Of the 171 samples studied, 33 (19.3%) presented positivity for
      Rotavirus A. Among positive samples, 72.7% belonged to male patients and 27.3% to
      female. Among the positive casuistic, 15.2% were vaccinated. When comparing the
      results obtained for the ELISA and Latex agglutination tests, 100% agreement
      between positivity by Latex agglutination and ELISA was verified. CONCLUSIONS:
      The high incidence of this infection reinforces the need to monitor this virus
      and define health policies concerning its diagnosis, prophylaxis, improvement in
      socioeconomic conditions and the refinement of the vaccine.

PMID- 21085868
TI  - [New records and epidemiological potential of certain species of mosquito
      (Diptera, Culicidae) in the State of Rio Grande do Sul, Brazil].
AB  - INTRODUCTION: Entomological surveillance has proven to be an important strategy
      for monitoring culicidae fauna, aimed at predicting the risk of exposure to
      pathogen vector species. The present work reports species identified for the
      first time in the State Rio Grande do Sul and discusses the epidemiological
      potential displayed by mosquito species occurring in Maquine municipality and in
      other regions of the State. METHODS: Mosquitoes were collected with Nasci vacuum
      and CDC light traps between December 2006 and December 2008, in the wild, rural
      and urban areas of Maquine. RESULTS: Fifty-five species were verified, of which
      22 were registered for the first time in the state and 10 are potential vector
      species for the Saint Louis, Oropouche, Aura, Trocara, Ilheus, Rocio, Una, West
      Nile, and eastern equine encephalitis viruses. CONCLUSIONS: These data
      demonstrate the importance of entomological surveillance as a tool for gathering
      information and promoting Health Surveillance actions.

PMID- 21085869
TI  - [Regional left ventricular dysfunction and its association with complex
      ventricular arrhythmia, in chagasic patients with normal or borderline
      electrocardiogram].
AB  - INTRODUCTION: Sudden death is the major cause of death among chagasic patients. A
      significant number of fatal events in patients without apparent heart disease and
      borderline electrocardiogram, but with contractile ventricular dysfunction, have
      been documented. This work aimed to determine the association between regional
      dysfunction and the presence of ventricular arrhythmia in chagasic patients
      without apparent heart disease. METHODS: Forty-nine patients with normal or
      borderline electrocardiogram were submitted to echocardiogram, exercise stress
      test and Holter. The presence of cardiac contractile alterations and complex
      ventricular arrhythmia was analyzed. Statistic analysis used the general Log
      Linear model. RESULTS: Mean age 56 years-old; 55% women. Regional ventricular
      dysfunction was verified in 24.5% of patients; positive Holter in 12% and
      exercise stress test in 18%. An association between complex ventricular
      arrhythmia and contractile abnormalities in the presence of mild left ventricle
      dysfunction was verified. CONCLUSIONS: Regional contractile abnormalities with
      mild left ventricle dysfunction in Chagasic patients indicate a group with higher
      risk of complex ventricular arrhythmias, who require specific follow-up.

PMID- 21085870
TI  - [Radiological study on megacolon cases in an endemic area for Chagas disease].
AB  - INTRODUCTION: A radiological study on the colon of patients from an endemic
      Chagas disease zone was conducted using the simplified opaque enema technique of
      Ximenes et al. METHODS: The study involved 291 individuals with a mean age of
      48.8 +/- 12.5 years-old, of whom 222 were seropositive for Chagas disease.
      Anteroposterior, posteroanterior and left lateral view radiographs were analyzed
      by visual inspection and measurement of the largest rectal and sigmoid diameters.
      RESULTS: From the visual inspection, megacolon was diagnosed in 14 (6.3%) Chagas
      disease patients. The mean diameter of the rectal ampulla among the Chagas
      patients was 6.3 +/- 1.0 cm, similar to the measurement in non-Chagas
      individuals: 6.2 +/- 1.0 cm (p= 0.391). The mean sigmoid loop diameter in the
      Chagas patients was 5 +/- 1.6 cm, which was larger than among the non-Chagas
      individuals: 4.4 +/- 0.8 cm (p= 0.001). CONCLUSIONS: excluding the evident and
      probable megacolon cases, the Chagas disease population continued to present a
      significantly larger mean sigmoid diameter than that observed among non-Chagas
      individuals (p= 0.003).

PMID- 21085871
TI  - [Use of an artificial neural network to predict the incidence of malaria in the
      city of Canta, state of Roraima].
AB  - INTRODUCTION: Malaria is endemic in the Brazilian Amazon region, with different
      risks for each region. The City of Canta, State of Roraima, presented one of the
      largest annual parasite indices in Brazil for the entire study period, with a
      value always greater than 50. The present study aimed to use an artificial neural
      network to predict the incidence of malaria in this city in order to assist
      health coordinators in planning and managing resources. METHODS: Data were
      collected on the website of the Ministry of Health, SIVEP--Malaria between 2003
      and 2009. An artificial neural network was structured with three neurons in the
      input layer, two intermediate layers and an output layer with one neuron. A
      sigmoid activation function was used. In training, the backpropagation method was
      used, with a learning rate of 0.05 and momentum of 0.01. The stopping criterion
      was to reach 20,000 cycles or a target of 0.001. The data from 2003 to 2008 were
      used for training and validation. The results were compared with those from a
      logistic regression model. RESULTS: The results for all periods provided showed
      that the artificial neural network had a smaller mean square error and absolute
      error compared with the regression model for the year 2009. CONCLUSIONS: The
      artificial neural network proved to be adequate for a malaria forecasting system
      in the city studied, determining smaller predictive values with absolute errors
      compared to the logistic regression model and the actual values.

PMID- 21085872
TI  - [Delayed diagnosis of malaria in a dengue endemic area in the Brazilian extra
      Amazon: recent experience of a malaria surveillance unit in state of Rio de
      Janeiro].
AB  - INTRODUCTION: The mortality of malaria in the extra-Amazon region is about 80
      times higher than in the Amazon region, where malaria is concentrated (99.8% of
      cases). In areas of dengue transmission, delay in the diagnosis and treatment of
      malaria in patients with fever who reside in areas of malaria transmission can be
      due to the confusion between the clinical diagnoses of both diseases by
      nonspecialist doctors, among other factors. This work presents some of the
      consequences of delayed diagnosis in three patients with malaria by Plasmodium
      falciparum, P. malariae and P. vivax, who, after following the usual route for
      Dengue treatment, sought our institution, where they were correctly diagnosed and
      adequately treated. METHODS: Description of three cases of malaria with delayed
      diagnosed malaria referred to the Outpatient Clinic for Acute Febrile Diseases,
      IPEC/FIOCRUZ-RJ, between 2007 and 2008. RESULTS: A Brazilian from Mozambique,
      primo-infected with P. falciparum was diagnosed with malaria six days after the
      onset of fever and died of cerebral malaria and shock. Another patient with
      P.malariae malaria presented a severe and prolonged course, but was cured after
      specific treatment. A third patient, with delayed diagnosis of P. vivax malaria,
      acquired it in the Atlantic Forest region in the State of Rio. CONCLUSIONS:
      Health professionals from non-endemic areas for malaria should be trained to
      optimize the surveillance and early treatment of malaria and prevent morbid and
      fatal outcomes. An investigation of outbreaks of autochthonous malaria in the
      State of Rio de Janeiro is suggested.

PMID- 21085873
TI  - [Identification by PCR and antifungal susceptibility of vaginal clinical Candida
      sp isolates].
AB  - INTRODUCTION: Vaginal candidiasis is a condition that affects innumerous fertile
      women. Candida albicans is the most frequently isolated species from vaginal
      discharge; however, other different species that are more resistant to antifungal
      drugs can be identified in vaginal clinical samples. METHODS: The species of 30
      vaginal Candida isolates was identified by PCR using the universal ITS4 primer
      and species-specific primers for C. albicans, C. glabrata, C. tropicalis and C.
      krusei. The sensitivity pattern to amphotericin B, fluconazole and voriconazole
      was assessed using the CLSI M27-A2 macrodilution method. RESULTS: The PCR assay
      revealed 28 C. albicans and 2 samples showed amplification for C. albicans and C.
      glabrata primers. The minimum inhibitory concentration for amphotericin B ranged
      from 0.03 ug/mL to 0.25 ug/mL, for fluconazole from 0.125 ug/ml to 16 ug/mL and
      for voriconazole from 0.03 ug/mL to 0.25 ug/m. CONCLUSIONS: Identification at
      Candida species level by PCR assay could be relevant for clinical management of
      these infections.

PMID- 21085874
TI  - [Physiotherapy intervention promotes better quality of life for individuals with
      pemphigus].
AB  - INTRODUCTION: Pemphigus is an autoimmune disease characterized by bullae, in
      which its chronicity and clinical manifestations generate alterations in the
      quality of life. In Brazil, the disease prevails in the states of the Midwest and
      Southeast. The study aimed to evaluate the profile and quality of life of
      patients with pemphigus in a Brazilian city, for the purposes of
      physiotherapeutic intervention. METHODS: The medical records of 15
      institutionalized patients were analyzed, though only 7 volunteers underwent the
      initial and final interviews using the quality of life questionnaire SF-36.
      Between data collections, physical therapy exercises were applied over a four
      month period. After this predetermined period the data were compared and analyzed
      quantitatively using the Med Calc E and the Student t test. RESULTS: The 15
      patients in treatment had a mean age of 40 years-old; 53.3% were melanoderm; 80%
      were men; 60% had contact with rural areas and 80% were from the southern region.
      The 7 patients who participated in the intervention showed a tendency for
      improvement in the areas assessed by the SF-36, except for vitality and social
      aspects. CONCLUSIONS: The profile of the population of this hospital is in
      agreement with the literature. According to the SF-36 collected before and after
      the physical therapy intervention, general improvement in the quality of life of
      these patients was verified. This research suggests that physiotherapeutic
      intervention promotes diverse benefits for patients with pemphigus.

PMID- 21085876
TI  - [Predatory activity of the nematophagous fungi Duddingtonia flagrans,
      Monacrosporium thaumasium and Arthrobotrys robusta on Strongyloides stercoralis
      infective larvae].
AB  - INTRODUCTION: Strongyloides stercoralis is a nematode that infects much of the
      population worldwide. METHODS: This study aimed to compare the ability of
      predatory nematophagous fungi Duddingtonia flagrans (AC001), Monacrosporium
      thaumasium (NF34) and Arthrobotrys robusta (I-31) on infective larvae (L3) of
      Strongyloides stercoralis in laboratory conditions on 2% water-agar. RESULTS: At
      the end of the experiment, the percentage reductions in Strongyloides stercoralis
      L3 were 83.7% (AC001), 75.5% (NF34) and 73.2% (I-31). CONCLUSIONS: The
      nematophagous fungi were able to capture and destroy the L3 in vitro and may be
      used as biological controls of Strongyloides stercoralis.

PMID- 21085875
TI  - [Air contamination levels in operating rooms during surgery of total hip and
      total knee arthroplasty, hemiarthroplasty and osteosynthesis in the surgical
      center of a Brazilian hospital].
AB  - INTRODUCTION: The air contamination levels during orthopedic surgeries were
      evaluated. METHODS: The air of operating rooms (ORs) was examined through
      exposure to microbiological plates placed near the surgical table for an hour.
      RESULTS: values above that recommended (369 CFU/m3) for conventional ORs and ORs
      with ultraclean air were determined. Contamination was predominantly by
      Staphylococcus sp (86.9%). In all surgeries a high number of people were present
      inside the ORs and the doors were opened frequently. CONCLUSIONS: The
      contamination levels are above the values accepted by regulatory agencies,
      representing risk for patients.

PMID- 21085877
TI  - [Sepsis, severe sepsis and septic shock: clinical, epidemiological and prognostic
      characteristics of patients in an intensive care unit in a university hospital].
AB  - INTRODUCTION: Sepsis is considered to be a severe disease with high mortality.
      The objective of this study was to determine the incidence and evolution of
      sepsis among critically ill patients. METHODS: Prospective surveillance of sepsis
      was performed in the adult intensive care unit, between April and December 2007.
      RESULTS: The patient frequency/day was 442. Seventy-five patients (18.6%) had
      sepsis and 72% of these cases were hospital-acquired. The rates of severe sepsis
      and septic shock per patient/day were 5.0 and 3.1, respectively. The total
      mortality was 34.6% and 61% of the cases had microbiological diagnoses.
      CONCLUSIONS: Sepsis presented with higher frequency than is usually described in
      the literature.

PMID- 21085878
TI  - [Parasitism by Amblyomma sp (Acari: Ixodidae) in humans in the City of Recife,
      State of Pernambuco, Brazil].
AB  - INTRODUCTION: The Amblyomma genus is widely distribution in Brazil and is
      important regarding the public health risk represented by the transmission of
      pathogens. METHODS: This paper reports a case of parasitism in humans by
      Amblyomma sp that occurred in the City of Recife, State of Pernambuco. RESULTS:
      Parasitism was observed in a woman where the ticks were attached to her legs and
      feet. CONCLUSIONS: This finding is unusual and is the first report of parasitism
      in humans by Amblyomma sp in State of Pernambuco.

PMID- 21085879
TI  - Piranha attacks in dammed streams used for human recreation in the State of Sao
      Paulo, Brazil.
AB  - In recent years, attacks by piranhas have become a common problem in dammed
      portions of rivers and streams in the State of Sao Paulo, Southeastern Brazil. In
      two outbreaks recorded in two neighboring counties in the Northwest region of the
      state, 74 bathers were bitten. Only one bite per person was recorded during a
      short period of the year. The bites were related to parental care and/or defense
      of spawning territory, which confirms previous studies and demystify the attacks
      by these legendary fish, as they are perceived by most people. Placement of fine
      mesh nets and removal of aquatic vegetation stopped the attacks.

PMID- 21085880
TI  - Clinical and evolutionary characteristics of four patients with pulmonary
      histoplasmosis reported in the Paraiba Paulista Valley region.
AB  - The type of pulmonary histoplasmosis presents limited lesions to the lungs, with
      symptoms that are clinically and radiological similar to chronic pulmonary
      tuberculosis. This paper describes the clinical features of four cases of
      pulmonary histoplasmosis. Aspects of diagnostic and clinical, epidemiological,
      laboratory and imaging exams are discussed, in addition to the clinical status of
      the individuals five years after disease onset. The treatment of choice was oral
      medication, following which all the patients improved. It is important to
      understand the clinical status and the difficulties concerning the differential
      diagnosis of histoplasmosis, to assist the proper indication of cases, thus
      reducing potential confusion with other diseases.

PMID- 21085881
TI  - [Hemorrhagic stroke related to snakebite by bothrops genus: a case report].
AB  - This research reports a clinical case of hemorrhagic stroke due to envenomation
      by bothrops snakebite associated with severe hypertension. Although bothrops
      snakebites are frequent in the State of Para, such associations are uncommon,
      requiring specialized and early management to avoid severe complications.

PMID- 21085882
TI  - [Sustained virological response in patients with coinfection by hepatitis C virus
      genotypes 1 and 2, after just nine weeks of antiviral therapy: case report].
AB  - A report of a 67 year-old male patient with positive serology for HCV. PCR
      revealed the presence of HCV RNA, viral load of 2,000 copies/mL and genotypes 1
      and 2. The patient was treated with peginterferon alfa-2a at 180 mcg/week and
      ribavirin at 1,000 mg/day. In week four of treatment, HCV viral load was
      undetectable. In week nine, the patient developed hematemesis, worsening of
      asthenia, anorexia and impaired general condition, so the treatment was
      discontinued. The PCR was negative six months and one year after the cessation of
      treatment. The patient remains asymptomatic.

PMID- 21085883
TI  - Left recurrent laryngeal palsy (Ortner's syndrome) in schistosomal pulmonary
      hypertension.

PMID- 21085884
TI  - Strategies to increase the sensitivity of pharmacovigilance in Portugal.
AB  - OBJECTIVE: To evaluate the results of an intervention to improve the number and
      relevance of reports of adverse drug reactions. METHODS: A cluster-randomized
      controlled trial was conducted with pharmacists working in Northern Portugal, in
      2007. After randomization, 364 individuals were placed into the intervention
      group (261 in telephone interviews and 103 in workshops), while the control group
      was comprised of 1,103 pharmacists. The following were approached in the
      educational intervention: the problem of adverse drug reaction, the impact on
      public health and spontaneous reporting. With regard to relevance, adverse
      reactions were classified into severe and unexpected. Statistical analysis was
      performed, based on the intention-to-treat principle; generalized linear mixed
      models were applied, using the penalized quasi-likelihood method. The pharmacists
      studied were followed during a period of 20 months. RESULTS: The intervention
      increased the rate of spontaneous reporting of adverse reactions three times (RR
      = 3.22; 95% CI 1.33;7.80), when compared to the control group. The relevance of
      reporting rose, with an increase in severe adverse reactions by approximately
      four times (RR = 3.87; 95% CI 1.29;11.61) and in unexpected adverse reactions by
      five times (RR = 5.02; 95% CI 1.33;18.93), compared to the control group.
      CONCLUSIONS: During a period of up to four months, educational interventions
      significantly increased the number and relevance of spontaneous reporting of
      adverse drug reactions by pharmacists in Northern Portugal.

PMID- 21085885
TI  - Direct medical costs associated with schizophrenia relapses in health care
      services in the city of Sao Paulo.
AB  - OBJECTIVE: To assess direct medical costs associated with schizophrenia relapses
      in mental health services. METHODS: The study was conducted in three health
      facilities in the city of Sao Paulo: a public state hospital; a Brazilian
      National Health System (SUS)-contracted hospital; and a community mental health
      center. Medical records of 90 patients with schizophrenia who received care in
      2006 were reviewed. Information on inpatient expenditures was collected and used
      for cost estimates. RESULTS: Mean direct medical cost of schizophrenia relapses
      per patient was US$ 4,083.50 (R$ 8,167.58) in the public state hospital; US$
      2,302.76 (R$ 4,605.46) in the community mental health center; and US$ 1,198.50
      (R$ 2,397.74) in the SUS-affiliated hospital. The main component was daily
      inpatient room rates (87% - 98%). Medication costs varied depending on the use of
      typical or atypical antipsychotic drugs. Atypical antipsychotic drugs were more
      often used in the community mental health center. CONCLUSIONS: Costs associated
      with schizophrenia relapses support investments in antipsychotic drugs and
      strategies to reduce disease relapse and the need for mental health inpatient
      services. Treating patients in a community mental health center was associated
      with medium costs and added the benefit of not depriving these patients from
      family life.

PMID- 21085886
TI  - Factors associated with breastfeeding in the first hour of life.
AB  - OBJECTIVE: To identify factors associated with breastfeeding in the first hour of
      life (Step 4 of the Baby-Friendly Hospital Initiative). METHODS: A cross
      sectional study was conducted with a representative sample of mothers who gave
      birth in maternity wards in the city of Rio de Janeiro, Southeastern Brazil,
      between 1999 and 2001. Newborns or mothers with restriction to breastfeeding were
      excluded, resulting in a sample of 8,397 pairs. A random effect--at maternity
      hospital level--Poisson model was employed in a hierarchical approach with three
      levels: distal, intermediate and proximal for characteristics of the mother, of
      the newborn, and of prenatal and hospital assistance. RESULTS: Only 16% of the
      mothers breastfed in the first hour of life. Breastfeeding in this period was
      less prevalent among neonates with immediate intercurrences after birth (PR =
      0.47; CI99% 0.15;0.80); among mothers who did not have contact with their
      newborns in the delivery room (PR = 0.62; CI99% 0.29;0.95); among mothers
      submitted to cesarean section delivery (PR = 0.48; CI99% 0.24;0.72); and among
      mothers who gave birth at private maternity hospitals (PR = 0.06; CI99%
      0.01;0.19) or at maternity hospitals contracted out to National Health System
      (SUS) (PR = 0.16; CI99% 0.01;0.30). The context effect of maternity wards was
      statistically significant. CONCLUSIONS: At an individual level, breastfeeding
      within one hour after birth was constrained by inappropriate practices in private
      or SUS-contracted maternity hospitals. The group effect of maternity hospitals
      and the absence of individual maternal-related factors that explain the outcome
      suggest that mothers have little or no autonomy to breastfeed their babies within
      the first hour of life, and depend on the institutional practices that prevail at
      the maternity hospitals.

PMID- 21085887
TI  - A clinical gamma camera-based pinhole collimated system for high resolution small
      animal SPECT imaging.
AB  - The main objective of the present study was to upgrade a clinical gamma camera to
      obtain high resolution tomographic images of small animal organs. The system is
      based on a clinical gamma camera to which we have adapted a special-purpose
      pinhole collimator and a device for positioning and rotating the target based on
      a computer-controlled step motor. We developed a software tool to reconstruct the
      target's three-dimensional distribution of emission from a set of planar
      projections, based on the maximum likelihood algorithm. We present details on the
      hardware and software implementation. We imaged phantoms and heart and kidneys of
      rats. When using pinhole collimators, the spatial resolution and sensitivity of
      the imaging system depend on parameters such as the detector-to-collimator and
      detector-to-target distances and pinhole diameter. In this study, we reached an
      object voxel size of 0.6 mm and spatial resolution better than 2.4 and 1.7 mm
      full width at half maximum when 1.5- and 1.0-mm diameter pinholes were used,
      respectively. Appropriate sensitivity to study the target of interest was
      attained in both cases. Additionally, we show that as few as 12 projections are
      sufficient to attain good quality reconstructions, a result that implies a
      significant reduction of acquisition time and opens the possibility for
      radiotracer dynamic studies. In conclusion, a high resolution single photon
      emission computed tomography (SPECT) system was developed using a commercial
      clinical gamma camera, allowing the acquisition of detailed volumetric images of
      small animal organs. This type of system has important implications for research
      areas such as Cardiology, Neurology or Oncology.

PMID- 21085888
TI  - Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation.
AB  - Clinically relevant animal models capable of simulating traumatic hemorrhagic
      shock are needed. We developed a hemorrhagic shock model with male New Zealand
      rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute
      care of a penetrating trauma victim in an urban scenario using current
      resuscitation strategies. A laparotomy was performed to reproduce tissue trauma
      and an aortic injury was created using a standardized single puncture to the left
      side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating
      mechanism. A 15-min interval was used to simulate the arrival of pre-hospital
      care. Fluid resuscitation was then applied using two regimens: normotensive
      resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals)
      and hypotensive resuscitation at 60% of baseline MAP (10 animals). Another 10
      animals were sham operated. The total time of the experiment was 85 min,
      reproducing scene, transport and emergency room times. Intra-abdominal blood loss
      was significantly greater in animals that underwent normotensive resuscitation
      compared to hypotensive resuscitation (17.1 +/- 2.0 vs 8.0 +/- 1.5 mL/kg).
      Antithrombin levels decreased significantly in normotensive resuscitated animals
      compared to baseline (102 +/- 2.0 vs 59 +/- 4.1%), sham (95 +/- 2.8 vs 59 +/-
      4.1%), and hypotensive resuscitated animals (98 +/- 7.8 vs 59 +/- 4.1%). Evidence
      of re-bleeding was also noted in the normotensive resuscitation group. A
      hypotensive resuscitation regimen resulted in decreased blood loss in a
      clinically relevant small animal model capable of reproducing hemorrhagic shock
      caused by a penetrating mechanism.

PMID- 21085889
TI  - Increased levels of glutamate in the central nervous system are associated with
      behavioral symptoms in experimental malaria.
AB  - Cerebral malaria (CM) is a severe complication resulting from Plasmodium
      falciparum infection. This condition has been associated with cognitive,
      behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms
      of CM are incompletely understood. Glutamate and other metabolites such as
      lactate have been implicated in its pathogenesis. In the present study, we
      investigated the involvement of glutamate in the behavioral symptoms of CM.
      Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P.
      berghei ANKA by the intraperitoneal route using a standardized inoculation of 106
      parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17)
      received the same volume of PBS. Behavioral and neurological symptoms were
      analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype
      Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral
      cortex and cerebrospinal fluid of infected and control mice by fluorimetric
      assay. All functional categories of the SHIRPA battery were significantly altered
      in the infected mice at 6 days post-infection (dpi) (P <= 0.05). In parallel to
      CM symptoms, we found a significant increase in glutamate levels in the cerebral
      cortex (mean +/- SEM; control: 11.62 +/- 0.90 nmol/mg protein; infected at 3 dpi:
      10.36 +/- 1.17 nmol/mg protein; infected at 6 dpi: 26.65 +/- 0.73 nmol/mg
      protein; with EGTA, control: 5.60 +/- 1.92 nmol/mg protein; infected at 3 dpi:
      6.24 +/- 1.87 nmol/mg protein; infected at 6 dpi: 14.14 +/- 0.84 nmol/mg protein)
      and in the cerebrospinal fluid (control: 128 +/- 51.23 pmol/mg protein; infected:
      301.4 +/- 22.52 pmol/mg protein) of infected mice (P <= 0.05). These findings
      suggest a role of glutamate in the central nervous system dysfunction found in
      CM.

PMID- 21085891
TI  - Effects of different levels of positive airway pressure on breathing pattern and
      heart rate variability after coronary artery bypass grafting surgery.
AB  - The application of continuous positive airway pressure (CPAP) produces important
      hemodynamic alterations, which can influence breathing pattern (BP) and heart
      rate variability (HRV). The aim of this study was to evaluate the effects of
      different levels of CPAP on postoperative BP and HRV after coronary artery bypass
      grafting (CABG) surgery and the impact of CABG surgery on these variables.
      Eighteen patients undergoing CABG were evaluated postoperatively during
      spontaneous breathing (SB) and application of four levels of CPAP applied in
      random order: sham (3 cmH2O), 5 cmH2O, 8 cmH2O, and 12 cmH2O. HRV was analyzed in
      time and frequency domains and by nonlinear methods and BP was analyzed in
      different variables (breathing frequency, inspiratory tidal volume, inspiratory
      and expiratory time, total breath time, fractional inspiratory time, percent rib
      cage inspiratory contribution to tidal volume, phase relation during inspiration,
      phase relation during expiration). There was significant postoperative impairment
      in HRV and BP after CABG surgery compared to the preoperative period and
      improvement of DFAalpha1, DFAalpha2 and SD2 indexes, and ventilatory variables
      during postoperative CPAP application, with a greater effect when 8 and 12 cmH2O
      were applied. A positive correlation (P < 0.05 and r = 0.64; Spearman) was found
      between DFAalpha1 and inspiratory time to the delta of 12 cmH2O and SB of HRV and
      respiratory values. Acute application of CPAP was able to alter cardiac autonomic
      nervous system control and BP of patients undergoing CABG surgery and 8 and 12
      cmH2O of CPAP provided the best performance of pulmonary and cardiac autonomic
      functions.

PMID- 21085890
TI  - Can course format influence the performance of students in an advanced cardiac
      life support (ACLS) program?
AB  - Advanced cardiac life support (ACLS) is a problem-based course that employs
      simulation techniques to teach the standard management techniques of
      cardiovascular emergencies. Its structure is periodically revised according to
      new versions of the American Heart Association guidelines. Since it was
      introduced in Brazil in 1996, the ACLS has been through two conceptual and
      structural changes. Detailed documented reports on the effect of these changes on
      student performance are limited. The objective of the present study was to
      evaluate the effect of conceptual and structural changes of the course on student
      ACLS performance at a Brazilian training center. This was a retrospective study
      of 3266 students divided into two groups according to the teaching model: Model 1
      (N = 1181; 1999-2003) and Model 2 (N = 2085; 2003-2007). Model 2 increased
      practical skill activities to 75% of the total versus 60% in Model 1.
      Furthermore, the teaching material provided to the students before the course was
      more objective than that used for Model 1. Scores greater than 85% in the
      theoretical evaluation and approval in the evaluation of practice by the
      instructor were considered to be a positive outcome. Multiple logistic regression
      was used to adjust for potential confounders (specialty, residency, study time,
      opportunity to enhance practical skills during the course and location where the
      course was given). Compared to Model 1, Model 2 presented odds ratios (OR)
      indicating better performance in the theoretical (OR = 1.34; 95%CI = 1.10-1.64),
      practical (OR = 1.19; 95%CI = 0.90-1.57), and combined (OR = 1.38; 95%CI = 1.13
      1.68) outcomes. Increasing the time devoted to practical skills did not improve
      the performance of ACLS students.

PMID- 21085892
TI  - Proteomic analysis of cytosolic proteins associated with petite mutations in
      Candida glabrata.
AB  - The incidence of superficial or deep-seated infections due to Candida glabrata
      has increased markedly, probably because of the low intrinsic susceptibility of
      this microorganism to azole antifungals and its relatively high propensity to
      acquire azole resistance. To determine changes in the C. glabrata proteome
      associated with petite mutations, cytosolic extracts from an azole-resistant
      petite mutant of C. glabrata induced by exposure to ethidium bromide, and from
      its azole-susceptible parent isolate were compared by two-dimensional
      polyacrylamide gel electrophoresis. Proteins of interest were identified by
      peptide mass fingerprinting or sequence tagging using a matrix-assisted laser
      desorption/ionization tandem time-of-flight mass spectrometer. Tryptic peptides
      from a total of 160 Coomassie-positive spots were analyzed for each strain. Sixty
      five different proteins were identified in the cytosolic extracts of the parent
      strain and 58 in the petite mutant. Among the proteins identified, 10 were higher
      in the mutant strain, whereas 23 were lower compared to the parent strain. The
      results revealed a significant decrease in the enzymes associated with the
      metabolic rate of mutant cells such as aconitase, transaldolase, and pyruvate
      kinase, and changes in the levels of specific heat shock proteins. Moreover,
      transketolase, aconitase and catalase activity measurements decreased
      significantly in the ethidium bromide-induced petite mutant. These data may be
      useful for designing experiments to obtain a better understanding of the nuclear
      response to impairment of mitochondrial function associated with this mutation in
      C. glabrata.

PMID- 21085893
TI  - Intravenous regional block is similar to sympathetic ganglion block for pain
      management in patients with complex regional pain syndrome type I.
AB  - Sympathetic ganglion block (SGB) or intravenous regional block (IVRB) has been
      recommended for pain management in patients with complex regional pain syndrome
      type I (CRPS-I). Forty-five patients were initially selected but only 43 were
      accepted for the study. The present study evaluated the efficacy of IVRB produced
      by combining 70 mg lidocaine with 30 ug clonidine (14 patients, 1 male/13
      females, age range: 27-50 years) versus SGB produced by the injection of 70 mg
      lidocaine alone (14 patients, 1 male/13 females, age range: 27-54 years) or
      combined with 30 ug clonidine (15 patients, 1 male/14 females, age range: 25-50
      years) into the stellate ganglion for pain management in patients with upper
      extremity CRPS-I. Each procedure was repeated five times at 7-day intervals, and
      pain intensity and duration were measured using a visual analog scale immediately
      before each procedure. A progressive and significant reduction in pain scores and
      a significant increase in the duration of analgesia were observed in all groups
      following the first three blocks, but no further improvement was obtained
      following the last two blocks. Drowsiness, the most frequent side effect, and dry
      mouth occurred only in patients submitted to SGB with lidocaine combined with
      clonidine. The three methods were similar regarding changes in pain intensity and
      duration of analgesia. However, IVRB seems to be preferable to SGB due to its
      easier execution and lower risk of undesirable effects.

PMID- 21085895
TI  - Evaluation of the immune humoral response of Brazilian patients with Rubinstein
      Taybi syndrome.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by
      craniofacial dysmorphisms, broad thumbs and toes, mental and growth deficiency,
      and recurrent respiratory infections. RTS has been associated with CREBBP gene
      mutations, but EP300 gene mutations have recently been reported in 6 individuals.
      In the present study, the humoral immune response in 16 RTS patients with
      recurrent respiratory infections of possible bacterial etiology was evaluated. No
      significant differences between patients and 16 healthy controls were detected to
      explain the high susceptibility to respiratory infections: normal or elevated
      serum immunoglobulin levels, normal salivary IgA levels, and a good antibody
      response to both polysaccharide and protein antigens were observed. However, most
      patients presented high serum IgM levels, a high number of total B cell and B
      subsets, and also high percentiles of apoptosis, suggesting that they could
      present B dysregulation. The CREBBP/p300 family gene is extremely important for B
      cell regulation, and RTS may represent an interesting human model for studying
      the molecular mechanisms involved in B-cell development.

PMID- 21085896
TI  - Follow-up of patients treated with retinoic acid for the control of radioiodine
      non-responsive advanced thyroid carcinoma.
AB  - During thyroid tumor progression, cellular de-differentiation may occur and it is
      commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic
      acid (RA) administration might increase iodine uptake in about 40% of patients,
      suggesting that RA could be a promising therapeutic option for radioiodine non
      responsive thyroid carcinoma, although a prospective study with a long-term
      follow-up has not been reported. This was a clinical prospective study assessing
      the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact
      on major outcomes such as tumor regression and cancer-related death with a long
      term follow-up of patients submitted to radioiodine (131I) therapy after RA
      administration. Sixteen patients with inoperable disease and no significant
      radioiodine uptake on post-therapy scan were selected. Patients were treated
      orally with 13-cis-RA at a dose of 1.0 to 1.5 mg.kg-1.day-1 for 5 weeks and then
      submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole
      body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST
      criteria were used to evaluate the response. An objective partial response rate
      was observed in 18.8%, a stable disease rate in 25% and a progression disease
      rate in 56.2%. Five patients died (62.5%) in the group classified as progression
      of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months,
      with a median PFS of 26.5 months. RA may be an option for advanced de
      differentiated thyroid cancer, due to the low rate of side effects.

PMID- 21085897
TI  - Women with primary ovarian insufficiency have lower bone mineral density.
AB  - The aim of the present study was to assess the prevalence of osteoporosis in a
      sample of 32 patients with spontaneous primary ovarian insufficiency (POI) in
      comparison to reference groups of 25 pre- and 55 postmenopausal women. Hip
      (lumbar) and spinal bone mineral density (BMD) measurements were performed by
      dual-energy X-ray absorptiometry in the three groups. The median age of POI
      patients at the time of diagnosis was 35 years (interquartile range: 27-37
      years). The mean +/- SD age of postmenopausal reference women (52.16 +/- 3.65
      years) was higher than that of POI (46.28 +/- 10.38 years) and premenopausal
      women (43.96 +/- 7.08; P = 0.001) at the time of BMD measurement. Twenty-seven
      (84.4%) POI women were receiving hormone replacement therapy (HRT) at the time of
      the study. In the postmenopausal reference group, 30.4% were current users of
      HRT. Lumbar BMD was significantly lower in the POI group (1.050 +/- 0.17 g/cm2)
      compared to the age-matched premenopausal reference group (1.136 +/- 0.12 g/cm2;
      P = 0.040). Moreover, 22 (68.7%) POI women had low bone density
      (osteopenia/osteoporosis by World Health Organization criteria) versus 47.3% of
      the postmenopausal reference group (P = 0.042). In conclusion, the present data
      indicate that BMD is significantly lower in patients with POI than in age-matched
      premenopausal women. Also, the prevalence of osteopenia/osteoporosis is higher in
      POI women than in women after natural menopause. Early medical interventions are
      necessary to ensure that women with POI will maintain their bonemass.

PMID- 21085898
TI  - 5-Bromo-2'-deoxyuridine induces visible morphological alteration in the DNA puffs
      of the anterior salivary gland region of Bradysia hygida (Diptera, Sciaridae).
AB  - 5-Bromo-2'-deoxyuridine (BrdUrd) has long been known to interfere with cell
      differentiation. We found that treatment of Bradysia hygida larvae with BrdUrd
      during DNA puff anlage formation in the polytene chromosomes of the salivary
      gland S1 region noticeably affects anlage morphology. However, it does not affect
      subsequent metamorphosis to the adult stage. The chromatin of the chromosomal
      sites that would normally form DNA puffs remains very compact and DNA puff
      expansion does not occur with administration of 4 to 8 mM BrdUrd. Injection of
      BrdUrd at different ages provoked a gradient of compaction of the DNA puff
      chromatin, leading to the formation of very small to almost normal puffs. By
      immunodetection, we show that the analogue is preferentially incorporated into
      the DNA puff anlages. When BrdUrd is injected in a mixture with thymidine, it is
      not incorporated into the DNA, and normal DNA puffs form. Therefore,
      incorporation of this analogue into the amplified DNA seems to be the cause of
      this extreme compaction. Autoradiographic experiments and silver grains counting
      showed that this treatment decreases the efficiency of RNA synthesis at DNA puff
      anlages.

PMID- 21085899
TI  - The modified 2VO ischemia protocol causes cognitive impairment similar to that
      induced by the standard method, but with a better survival rate.
AB  - Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has
      been established as a valid experimental model to investigate the effects of
      chronic cerebral hypoperfusion on cognitive function and neurodegenerative
      processes. Our aim was to compare the cognitive and morphological outcomes
      following the standard 2VO procedure, in which there is concomitant artery
      ligation, with those of a modified protocol, with a 1-week interval between
      artery occlusions to avoid an abrupt reduction of cerebral blood flow, as
      assessed by animal performance in the water maze and damage extension to the
      hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected
      to chronic hypoperfusion by permanent bilateral ligation of the common carotid
      arteries using either the standard or the modified protocol, with the right
      carotid being the first to be occluded. Three months after the surgical
      procedure, rat performance in the water maze was assessed to investigate long
      term effects on spatial learning and memory and their brains were processed in
      order to estimate hippocampal volume and striatal area. Both groups of
      hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001)
      and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) =
      21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no
      evidence of tissue atrophy was found in the brain structures studied. Despite
      similar behavioral and morphological outcomes, the rats submitted to the modified
      protocol showed a significant increase in survival rate, during the 3 months of
      the experiment (P < 0.02).

PMID- 21085901
TI  - Association of anthropometric, body composition and physiological measures with
      physical activity level among the children and adolescents of Asian Indian
      origin: the Calcutta obesity study.
AB  - OBJECTIVE: To look into the association between anthropometric, body
      compositional and physiological characteristics with physical activity among the
      children and adolescents of Asian Indian origin. METHODS: A total of 469 children
      and adolescents (250 boys and 219 girls) aged 8-18 years took part in the present
      cross-sectional study. A pre-designed schedule was used to collect information on
      socioeconomic characteristics and type of activities performed by them. RESULTS:
      It was observed that there was an inversely proportional trend for different
      anthropometric, body compositional and physiological measures with the duration
      of different types of physical activities. Moreover, walking, cycling and racing
      were observed to be correlated inversely with sum of four skinfold (SF4) and the
      ratio of SF4 and BMI (SF4: BMI). Furthermore, significant (p < 0.01) inverse
      correlation was observed in case of mean arterial pressure (MAP) with the
      duration of walking, cyclicing and gym. It was observed that about 14% (R2 =
      0.14) of the total variance of MAP was explained by duration of different types
      of physical activity and parental characteristics. CONCLUSIONS: Habitual moderate
      physical activity may be beneficial to prevent excess accumulation of fat during
      childhood and adolescence and warranted further investigation about the
      importance of physical activity to prevent increasing trend of childhood obesity.

PMID- 21085900
TI  - Adequacy and change in nutrient and food intakes with aging in a seven-year
      cohort study in elderly women.
AB  - OBJECTIVE: As women age total dietary intake falls which may increase the risk of
      dietary deficiencies in some individuals. The aims of this study were to
      investigate the changes in nutrient and dietary intakes that occurred with aging
      in a seven-year longitudinal study of elderly Australian women and to evaluate
      the adequacy of their dietary intakes. DESIGN: Longitudinal population based
      study on health with ageing. PARTICIPANTS AND SETTING: 911 free-living elderly
      women aged 70-85 years at baseline from a cohort of 1500 elderly women.
      MEASUREMENTS: At baseline, 60 and 84 months, self-reported Food Frequency
      Questionnaires (FFQ) and demographics were collected and anthropometry measured.
      RESULTS: During the 84 month subjects lost height (1.8 cm) and body weight (1.9
      kg). Intakes of energy and macronutrients carbohydrate, fat and protein declined
      significantly over the 84 months. Mean energy derived from saturated fat was
      above, whereas energy derived from carbohydrate was below, recommended levels of
      intake at all time points. Intakes of vitamins and minerals all declined with age
      and subjects had suboptimal intakes of folate, vitamin E and calcium at all time
      points. The serve sizes for potato and meat and the consumption of milk, bread
      and variety of vegetables declined significantly over time reflecting changes in
      nutrient intake. CONCLUSIONS: Ageing is associated with reduced food intake
      resulting in inadequate intakes in energy, and some nutrients. Nutrition policy
      for elderly women should include advice to maintain or increase intakes of
      carbohydrate, milk, vegetables and fruit whilst continuing to reduce fat intake.

PMID- 21085902
TI  - How is the risk of undernutrition associated with cardiovascular disease among
      individuals of advanced age?
AB  - BACKGROUND: The oldest old (85+) are the fastest growing population segment in
      New Zealand. Cardiovascular disease (CVD) is the main cause of death and is
      associated with various risk factors including risk of undernutrition.
      OBJECTIVES: To determine if there is an association between CVD and nutrition
      risk in advanced age. SETTING: Three North Island locations (rural and urban
      areas) in New Zealand. PARTICIPANTS: 108 participants aged 85 years (75-79 for
      Maori). MEASUREMENTS: Comprehensive health assessments were undertaken.
      Clinically manifest CVD was pre-defined and ascertained from interviews and
      hospitalisation records. Nutrition risk was assessed using a validated
      questionnaire-Seniors in the Community: Risk evaluation for eating and nutrition,
      Version II (SCREEN II). RESULTS: 72 participants (67%) had CVD (49% men); 52% of
      participants had a SCREEN II score < 50. Those with CVD had lower HDL level
      [median(IQR)] [1.4(0.7) vs. 1.6(0.6)] (p=0.041), and higher waist circumference
      [97.5(19.1) vs. 89.3(20.6)] (p=0.043) compared to those without CVD. Those with
      CVD were at no greater nutrition risk than those without CVD (SCREEN II score:
      [49(7) vs. 51(10)] (p=0.365). Using logistic regression controlling for
      confounders, SCREEN II scores trended towards an inverse association with CVD
      (p=0.10). CONCLUSION: Two thirds of the study participants had CVD and half were
      at risk of undernutrition. Nutrition risk was mildly associated with CVD. This
      study provides further evidence that those in advanced age are at risk of
      undernutrition. Further research is needed to establish how the causes and
      consequences of CVD are related to nutrition risk.

PMID- 21085903
TI  - Accuracy of Siri and Brozek equations in the percent body fat estimation in older
      adults.
AB  - OBJECTIVE: To identify which equation, Siri or Brozek, based on the two
      compartment model, provides a more accurate conversion of body density (BD) in
      percent body fat (%BF) in a group of older adults. STUDY DESIGN: Cross-sectional
      study. SETTING: Research Centre in Physical Activity, Health and Leisure, Faculty
      of Sport, University of Porto. PARTICIPANTS: 60 older adults, aged 60-92 years.
      MEASUREMENTS: Skinfold thickness was used to estimate BD through Visser et al.
      prediction equation. The conversion of BD to %BF was done with Siri (%BF-Siri)
      and Brozek (%BF-Brozek) formulas and these determined values were both compared
      to Dual-Energy X-ray Absorptiometry (%BF-DXA) evaluations. RESULTS: A strong
      correlation between the %BF-DXA value and %BF-Siri (r=0.91, p < 0.001) and %BF
      Brozek (r=0.91, p < 0.001) was found, although %BF-Siri and %BF-Brozek
      overestimated %BF-DXA (p < 0.001). The comparison of the %BF-Siri and %BF-Brozek
      mean values also revealed significant differences (p < 0.001). The %BF-Brozek
      reflects a better agreement than the %BF-Siri with %BF-DXA with respectively a
      mean difference of -4.0 %BF (limits of agreement = -10.9 to 2.9%) and -5.7 %BF (
      12.6 to 1.2). The Bland and Altman plots confirmed that %BF-Brozek reflects a
      better agreement with %BF-DXA. CONCLUSION: The results of the present study show
      that the use of Brozek equation may correspond to a more accurate alternative
      than Siri equation for the conversion of BD in %BF in older adults.

PMID- 21085904
TI  - Signs of cognitive decline in the elderly population.

PMID- 21085905
TI  - Central auditory processing in aging: the dichotic listening paradigm.
AB  - OBJECTIVE: Aging is associated with cognitive changing. Central auditory
      processing dysfunction may explain some understanding difficulties in elderly. It
      may be evaluated with the dichotic listening (DL) test, a widely-used
      experimental paradigm for studying inter-hemispheric interactions and attentional
      processes. This study examines central auditory language processing with a
      dichotic listening task in right-handed old subjects according to their age.
      DESIGN: Cross sectional-study. SETTING: memory clinic and geriatric unit.
      PARTICIPANTS: Adult group (Ad) consisted in 26 subjects (21 women and 5 men) aged
      50-69 years and an old adults group (Old-Ad) consisted in 20 subjects (19 women
      and 1 man) aged 70 to 89 years. MEASUREMENTS: DL consisted in a free-recall word
      task and a digit forced-attention task (forced-right: FR and forced-left: FL) in
      order to study central auditory language processing. In addition, we used
      neuropsychological tests to study executive functions and cognitive control,
      sustained by the prefrontal cortex. RESULTS: In the free recall condition, we
      confirmed the classic right ear advantage (REA) in both groups, particularly in
      older subjects. In the forced condition, we observed an ear advantage with a
      change in ear asymmetry as a consequence of instruction: REA in FR and a left-ear
      advantage (LEA) in FL. We compared contaminations by the contra-lateral
      inattentive ear: reports of the left ear (LE) in the FR condition and reports of
      the right ear (RE) in the FL condition. Contaminations by the RE in the FL
      condition were more pronounced in Old-Ad suggesting difficulties in competition
      between the natural tendency for the RE and the instruction. In the Old-Ad group,
      the correlation between the RE score in FL and TMT B-A/A suggests an impairment
      in mental flexibility. CONCLUSION: DL may be helpful to study central auditory
      dysfunction in aging. Our results suggest difficulties in attentional control and
      executive functions. Central auditory dysfunction should be evaluated in elderly
      because it potentially contributes to difficulty of hearing in noisy environment
      with consequences in the rehabilitation of presbyacousic subjects. More studies
      are needed to investigate the predictive value of DL as a marker of cognitive
      decline, particularly executive functions.

PMID- 21085906
TI  - Transforming growth factor beta and soluble endoglin in the healthy senior and in
      Alzheimer's disease patients.
AB  - OBJECTIVES: Senescence of the immune system and of endothelial cells can
      contribute to age-dependent vascular and neurodegenerative disorders including
      Alzheimer's disease. The aim of this study is an assessment of putative
      relationships of serum levels of transforming growth factor beta (TGFbeta) and
      soluble endoglin (sCD105) and neurodegeneration, and of changes of these
      molecules in the course of ageing. DESIGN: The subjects of the study consisted of
      three groups, the first one was 63 otherwise healthy middle - aged participants,
      31 females, 32 males, of average age 35 years. The second group was formed by 58
      healthy, self-dependent inhabitants of nursing homes, 44 females and 14 males,
      average age 83.5 years. The third group comprised of 129 Alzheimer's disease
      patients, 86 females, 43 males, of average age 80 years, with MMSE score that
      ranged from 16 to 20. MEASUREMENT: Serum levels of TGF beta and soluble endoglin
      were measured by the ELISA method in samples of peripheral blood using commercial
      kits. RESULTS: The serum level of TGFbeta was 34,339 +/- 6,420 pg/ml in the
      healthy younger group, 37,555 +/- 11,944 pg/ml in the healthy seniors, and 29,057
      +/- 11,455 pg/ml in Alzheimer's disease patients. Compared to healthy seniors,
      the serum level of TGFbeta was significantly decreased in Alzheimer's disease
      patients (p < 0.01). The serum level of endoglin were 4.88 +/- 0.95 MUg/ml in the
      healthy younger group; 6.11 +/- 1.38 MUg/ml in healthy seniors, and 7.20 +/- 1.72
      MUg/ml in patients with Alzheimer's disease, respectively. The serum level of
      endoglin was significantly higher (p < 0.001) in senescent healthy persons
      compared to the younger control group. When compared with healthy seniors,
      patients with Alzheimer's disease had significantly elevated (p < 0.001) serum
      level of endoglin. CONCLUSIONS: Decreased levels of TGF beta in Alzheimer's
      disease may result in impairment of cerebral circulation reflected in the
      increased endoglin levels. These findings may indicate involvement of the immune
      system in Alzheimer's disease pathogenesis.

PMID- 21085907
TI  - Effect of vitamin E supplementation with exercise on cognitive functions and
      total antioxidant capacity in older people.
AB  - OBJECTIVE: We investigated the effects of six months vitamin E administration on
      cognition evaluated by event-related potentials in exercising older subjects.
      DESIGN: Randomised controlled trial. SETTING: Retirement home in Antalya, Turkey.
      PARTICIPANTS: Fifty-seven adults aged 60-85 years were randomly assigned to one
      of four groups: sedentary control (C), vitamin E (V), exercise training (E) and
      vitamin E under training (EV). INTERVENTION: V and EV groups were received
      vitamin E at a dose of 900 IU/day P.O. for 6 months. Trained groups were
      subjected to walking exercise involved 3 sessions per week for 6 months. Walking
      duration was gradually increased during 8 weeks, and stayed constant until the
      end of training period. Participants were begun walking at % 70 heart rate
      reserve for 20 min/day at the first two weeks, and walking duration was increased
      by 5 minutes/day of each week until subjects were reached a level of 50 min/day
      by week 8. MEASUREMENTS: Plasma vitamin E concentration, total antioxidant
      capacity and two parameters of event-related potentials namely P3 latency and
      amplitude were performed on all study groups both before and after training.
      RESULTS: Significant improvement in P3 latency was found in exercising groups.
      However, no significant differences were found between vitamin and other groups
      for P3 latency. Amplitude measurements were found unaltered among all groups.
      CONCLUSION: We concluded that although six months training results improvement in
      P3 latency, vitamin E supplementation does not affect cognitive function
      evaluated by event-related potentials in older subjects.

PMID- 21085908
TI  - Memantine benefits functional abilities in moderate to severe Alzheimer's
      disease.
AB  - OBJECTIVE: Functional abilities are severely impacted in Alzheimer's disease
      (AD). Loss of the ability to perform complex (instrumental) and basic activities
      of daily living (ADL), leads to decreased independence and increased caregiver
      burden. This post-hoc analysis investigated the effect of memantine (20 mg/day)
      on ADLs, as measured by Alzheimer's Disease Cooperative Study-Activities of Daily
      Living 19-item (ADCS-ADL19) and 23-item (ADCS-ADL23) scales, in patients with
      moderate-to-severe AD. DESIGN: Data were pooled from six multicenter, randomized,
      placebo-controlled, double-blind, 6-month studies of memantine 20 mg/day.
      PARTICIPANTS: Male and female patients aged >= 50 years at baseline with a Mini
      Mental State Examination (MMSE) score < 20. MEASUREMENTS: ADCS-ADL19 and ADCS
      ADL23 scales were pooled, and 14 shared items, with a score range of 0-45, were
      identified and included in the analysis (ADL14). Basic ADLs (BADLs) were defined
      as: eating, walking, toileting, bathing, and grooming. Instrumental ADLs (IADLs)
      were defined as: using a telephone, watching television, conversing, clearing a
      table, finding belongings, obtaining a beverage, disposing of household rubbish,
      travelling outside the house, and being left alone. Changes from baseline on
      single-item, BADL (range: 0-15), IADL (range: 0-30), and total ADL14 scores were
      analysed for observed cases using ANCOVA, with study, center and treatment as
      categorical explanatory variables and score at baseline as a covariate. RESULTS:
      959 patients were treated with memantine and 867 patients received placebo.
      Memantine-treated patients had less decline from baseline on the ADL14 total
      score, compared with placebo (p < 0.001) at study end. Memantine also showed
      lower reductions in BADLs (p < 0.05) and IADLs (p < 0.001), for observed cases,
      compared with placebo. Memantine-treated patients showed less worsening than
      placebo recipients for the ADL items: toileting (p < 0.01), grooming (p < 0.01),
      finding belongings (p < 0.01), and travelling outside the house (p < 0.05).
      CONCLUSION: Compared with placebo, memantine shows benefits for both basic and
      instrumental ADLs in patients with moderate-to-severe AD, suggesting that
      memantine treatment may lead to a more interactive and dignified life for
      patients with moderate-to-severe AD.

PMID- 21085909
TI  - Foodservice satisfaction domains in geriatrics, rehabilitation and aged care.
AB  - OBJECTIVE: To develop a foodservice satisfaction instrument for residential aged
      care and geriatric/rehabilitation units. The quality of care and food provided
      for clients in long-term care facilities is critical for the prevention of
      malnutrition. DESIGN: Cross-sectional survey and in-depth interviews. SETTING:
      Nine residential aged care facilities and two geriatric/rehabilitation units in
      Southeast Queensland, Australia. PARTICIPANTS: A total of 103
      geriatric/rehabilitation patients and 210 aged care residents. The median age was
      84 years, with 72.1 % females. MEASUREMENTS: Candidate satisfaction items were
      obtained from: (i) secondary analysis of acute care foodservice satisfaction
      data; (ii) focus groups with expert geriatrics/rehabilitation and aged care
      dietitians; (iii) pre-testing of instrument content, presentation format and
      response-scale (n=40) and (iv) pilot testing of the instrument (n=313). Sixty-one
      items on foodservice attributes, an overall satisfaction question, and
      demographic/contextual information were tested. RESULTS: Principal components
      factor analysis and Velicer's MAP test revealed foodservice satisfaction was
      represented by 18 items within four factors: meal quality and enjoyment (alpha
      =0.91), autonomy (alpha =0.64), staff consideration (alpha =0.79), hunger and
      food quantity (alpha =0.67) and six independent items, totalling 24 foodservice
      characteristics. This represented around 40% of the variance in foodservice
      satisfaction. When a further 13 foodservice items were retained due to practical
      importance, the analysis explained around 64% of the variance in foodservice
      satisfaction. CONCLUSION: The Resident Foodservice Satisfaction Questionnaire is
      a novel measure of resident foodservice satisfaction and can be used to provide
      evidence for changes to food services that may improve or enhance resident
      satisfaction and assist in the prevention of a significant and modifiable cause
      of malnutrition.

PMID- 21085911
TI  - Risk factors for falling in community-dwelling older adults: which of them are
      associated with the recurrence of falls?
AB  - BACKGROUND: The aim of the study was to determine which risk factors were
      associated with the recurrence of falls among community-dwelling older adults.
      METHODS: Based on a cross-sectional design, 1066 community-dwelling volunteers
      aged 65 and older were recruited. The use of psychoactive drugs, the number of
      drugs taken per day, the basic mobility assessed with the Timed Up & Go test
      (TUG), the maximal isometric voluntary contraction strength of hand, the lower
      limb proprioception, the distance binocular vision, the fear of falling and the
      history of falls during the past year were recorded. Subjects were separated into
      4 groups based on the number of falls: 0, 1, 2 and >= 2 falls. RESULTS: Among the
      395 (37.1%) fallers, 291 (27.3%) were single fallers and 104 (9.8%) were
      recurrent fallers (i.e., > 2 falls). The numbers of falls increased significantly
      with age (Incident Rate Ratio (IRR)=1.03, p < 0.001), female gender (IRR=1.95, p
      < 0.001), institutionalization (IRR=1.66, p=0.002), number of drugs taken per day
      (IRR=1.05, p < 0.001), use of psychoactive drugs (IRR=1.29, p=0.009), increased
      time of TUG Test (IRR=1.02, p < 0.001), use of a walking aid (IRR=1.59, p=0.002),
      and fear of falling (IRR=3.08, p < 0.001). In addition, a high score at the
      handgrip test (IRR=0.97, p < 0.001) and distance binocular vision (IRR=0.92, p <
      0.001) were associated with a decreased number of falls. After adjustment for
      potential confounders, only female gender (IRR=1.44, p < 0.001), vision
      (IRR=0.95, p=0.006) and lower limb proprioception (IRR=0.95, p=0.046), and fear
      of falling (IRR=2.68, p < 0.001) were still significantly associated with the
      number of falls. CONCLUSION. The current study shows that female gender, poor
      vision and lower limb proprioception, and fear of falling were associated with
      the recurrence of falls.

PMID- 21085910
TI  - Waist-to-height ratio, an optimal predictor for obesity and metabolic syndrome in
      Chinese adults.
AB  - OBJECTIVE: Anthropometric indices to obesity were evaluated as predictors of
      metabolic syndrome risk factors. Our purpose was to explore an optimal or more
      reliable anthropometric indicator and optimal cut-off points for obesity on
      metabolic syndrome in Chinese adults. PARTICIPANTS AND METHODS: The survey was
      conducted involving 2947 participants, aged 20 or above with cross-sectional
      study of population. The predictive validity and optimal cut-off values were
      analyzed by receiver operating characteristic (ROC) curves, area under curve
      (AUC) and the largest Youden's index (sensitivity + specificity - 1) by gender
      group, respectively. Kappa value showed diagnostic consistency. RESULTS:
      According to the criteria of CDS 2004, IDF 2005 and AHA/NHLBI 2005, the
      prevalence of metabolic syndrome was 10.32%, 9.64% and 16.12% respectively, which
      indicated that the prevalence was higher in men than in women and increased with
      age (P < 0.05). The BMI, WC, WHR and WHtR in metabolic syndrome patients were
      greater than those in healthy volunteers and the indices in men were higher than
      those in women. With adjusted age and gender, the partial correlation coefficient
      for BMI-WC, BMI-WHR and BMI-WHtR was 0.7991, 0.5278 and 0.8196, respectively (P <
      0.05). The area under curves (AUCs) of receiver operating characteristic (ROC)
      curves for WHtR was larger (P < 0.05) than that for WC and WHR. The cut-point of
      WHtR was approximately 0.5 in both genders with a satisfactory balance between
      sensitivity and specificity, where the Kappa (k) value for WHtR-BMI was higher
      than that for WHtR-WHR, and WHtR-WC. CONCLUSIONS: The results indicated that WHtR
      might be an optimal anthropometric predictor of metabolic syndrome risk factors
      and the cut-point of WHtR was approximately 0.50 in both genders of Chinese
      adults.

PMID- 21085912
TI  - The correlation between the telomeric parameters and the clinical laboratory data
      in the patients with brain infarct and metabolic disorders.
AB  - OBJECTIVE: To elucidate the correlation between the telomere length and
      subtelomeric methylated status in peripheral leukocytes and the laboratory data
      of inpatients with brain infarction and metabolic disorders. This is the first
      report describing a link between routine clinical laboratory data and genomic
      aging. DESIGN: Cross-sectional population-based study. SETTING: Chronic disease
      ward of Kyushu University Hospital at Beppu in Japan. PARTICIPANTS: Inpatients
      with brain infarction and metabolic disorders. MEASUREMENTS: The laboratory data
      of male patients were collected and the telomeric parameters in their peripheral
      leukocytes were determined by a Southern blot analysis with methylation-sensitive
      and insensitive isoschizomers. Any correlations between the laboratory data and
      the telomeric parameters were assessed. RESULTS: The patients revealed a
      significant correlation among the fasting blood sugar, HbA1c, serum creatinine
      and urea nitrogen levels with the mean telomere length, expression of long
      telomeres ( > 9.4 kb), or the subtelomeric hypermethylation status of long
      telomeres. CONCLUSION: Our results suggested that the hyperglycemia and renal
      function of patients with metabolic disorders correlated positively with the
      aging-associated telomeric changes.

PMID- 21085913
TI  - Two cases of primary hyperparathyroidism with depressive and cognitive symptoms.

PMID- 21085914
TI  - Development of an integrated chronic obstructive pulmonary disease service model
      in an inner-city region in the UK: initial findings and 12-month results.
AB  - AIMS: To improve the management of chronic obstructive pulmonary disease (COPD)
      in Salford, UK, and to evaluate the impact of an integrated service model after
      one year. METHODS: A health needs analysis and benchmarking exercise was
      undertaken in 2007. These activities were used to develop an integrated service
      model in order to improve the diagnosis and management of COPD and reduce
      unscheduled hospital admissions and length of stay. RESULTS: Following
      implementation of the model, 811 further patients were diagnosed. Unscheduled
      hospital admissions for COPD fell from 935 to 840, length of stay was reduced
      from 8.3 to 7.7 days, and associated costs fell from L1,772, 865 to L1,528,080.
      The number of patients who completed pulmonary rehabilitation increased from 84
      to 143. CONCLUSIONS: An integrated COPD service model was successful in
      increasing diagnosis, reducing hospital admissions and reducing length of
      hospital stay - in line with the proposed National Strategy for COPD Services in
      England. It also promoted management according to National Institute of Health
      and Clinical Excellence (NICE) guidelines.

PMID- 21085915
TI  - The use of roflumilast in COPD: a primary care perspective.
AB  - Therapeutic interventions in chronic obstructive pulmonary disease (COPD) shown
      to reduce exacerbations include smoking cessation, vaccination and appropriate
      pharmacological therapy. Long-acting bronchodilators are the cornerstone of COPD
      pharmacotherapy, whereas inhaled corticosteroids and mucolytics have shown
      benefit in subgroups of patients. Despite management with existing therapies,
      clinical trials confirm the persistent nature of exacerbations throughout the
      course of the disease. Roflumilast - a phosphodiesterase-4 (PDE4) inhibitor -
      received European Marketing Approval in 2010 and represents a new class of drug
      in the management of COPD. Through selective inhibition of the PDE4 enzyme,
      roflumilast prevents the breakdown of cyclic AMP, which plays an important role
      in regulating inflammatory cell activity. Early trials in patients with a forced
      expiratory volume in one second (FEV1) less than 50% predicted suggest that
      roflumilast offers sustained and significant improvement in lung function and a
      reduction in exacerbations compared with placebo, irrespective of concomitant
      bronchodilator therapy. Common adverse events include headache, diarrhoea and
      weight loss, with the majority occurring at the beginning of treatment, being
      transient and not leading to sequelae. Serious adverse events tended to be low
      across all studies. Roflumilast is currently licensed in Europe, and is indicated
      as maintenance treatment in severe COPD (i.e. in patients with post
      bronchodilator FEV1 <50% predicted) associated with chronic bronchitis in adult
      patients with a history of frequent exacerbations as an add-on to bronchodilator
      treatment. Clear identification of patients eligible for roflumilast will require
      improved characterisation and phenotyping of patients in primary care, including
      lung function measurement, accurate health status classification, and recording
      of chronic cough and regular sputum production.

PMID- 21085916
TI  - Prevalence and characteristics of lung function changes in recreational scuba
      divers.
AB  - AIMS: To investigate the hypothesis that a salt water SCUBA dive may cause
      bronchoconstriction in some individuals. METHODS: 100 experienced recreational
      SCUBA divers acted as their own controls. Spirometry measures were taken with
      Easyone(TM) spirometers before and after a dive. Measures recorded included
      FEV1/FVC ratio and forced mid-expiratory flow (FEF25-75%). RESULTS: 60
      participants (68% male, 32% female) aged between 19-68 years (mean 47 years)
      produced data meeting ATS/ERS international standards. Of these, 23% exhibited
      pre-dive FEV1/FVC ratio values less than 75%. Statistics on paired samples of pre
      and post-parameters showed a significant decrease in FVC post-dive but did not
      show significant reductions in FEV1 or FEV1/FVC. Six (10%) were current smokers
      and 13 (21%) were former smokers. CONCLUSIONS: 25% of participants had reduced
      FEV1/FVC ratio regardless of undertaking a dive. Consideration of the clinical
      implications requires further investigation.

PMID- 21085917
TI  - [No cancer prevention with fundoplication : Results of a population-based study
      in Sweden].

PMID- 21085918
TI  - [Disappearing borders between cardiology and cardiothoracic surgery: status quo].
AB  - Cardiology and cardiothoracic surgery are closely related so that collaboration
      and communication are required to offer optimal therapy for patients. During the
      last decades many innovations have reduced the borders between cardiology and
      cardiothoracic surgery. Today, cardiologists may perform coronary interventions
      with good results that would have previously been the domain of coronary bypass
      surgery. In addition new valvular interventions have been developed, such as
      transfemoral or transapical aortic valve implantation and endovascular mitral
      valve reconstruction. New developments in cardiothoracic surgery have led to less
      invasive procedures and many surgical procedures can now be performed with
      minimally invasive techniques and without a cardiopulmonary bypass. To enable
      optimal therapy for patients, closer collaboration between cardiologists and
      cardiothoracic surgeons is required setting the stage for individualized therapy
      in the future.

PMID- 21085919
TI  - [Possibilities and limitations of the early identification of developmental
      language disorders].
AB  - BACKGROUND: It is not been proven to date that children with developmental
      language disorders can be identified by general language screening in 2-year-old
      children. The goal of the present study was to determine the predictive
      diagnostic power of the parent questionnaire SBE-2-KT. METHODS: The language
      abilities of 562 children were assessed using the SBE-2-KT at the age of 2 and
      reassessed 1 year later using the parent questionnaire SBE-3-KT. RESULTS: The
      correlation between language scores at age 2 and 3 were moderate and highly
      significant (rSp=0.59-0.68, p<0.001). Sensitivity, specificity, as well as
      positive and negative predictive values against language impairment at age 3 as a
      reference were 43%, 93%, 57% and 88%, respectively. CONCLUSIONS: The possibility
      to identify children with language disorders at the age of 2 is limited. Almost
      half of the children with delayed language development at age 2 had results on
      language screening within the normal range at 3 years. Furthermore, nearly every
      second child with subnormal language scores at age 3 is not classified as a late
      talker at age 2. Therefore, for early identification of language disorders a
      general reassessment of language skills is necessary at the age of 3.

PMID- 21085920
TI  - [Obstructive sleep apnea in children].
AB  - Obstructive sleep apnea (OSA) is a common disease in children. It is defined by
      the onset of snoring, hypopneas or apneas with impaired sleep and daytime
      function. Obstruction of the upper airway during sleep is the underlying
      pathogenetic mechanism. It is caused either by an anatomic obstruction, increased
      airway collapsibility or both. Normally OSA in children is diagnosed by its
      typical anamnesis including snoring and exerted breathing patterns. The diagnosis
      is confirmed in unclear cases using polysomnography. Treatment consists of
      conservative measures such as weight reduction and--provided appropriate
      anatomical findings exist--adenotonsillectomy or adenotonsillotomy. Surgery is an
      effective treatment for OSA in children as proven by numerous studies of high
      evidence levels.

PMID- 21085921
TI  - [Intraorbital wooden foreign body undetected on CT].
AB  - We present the case of an orbital fracture and a wooden foreign body found during
      surgery. The patient had undergone a pre-operative computed tomography scan but
      the foreign body had not been seen on these images. We discuss the difficulties
      in demonstrating wooden objects on CT and describe indicators in patient history,
      examination findings and radiological signs that might suggest the presence of a
      wooden object. We emphasise the necessity to explore any orbital injury if there
      are clinical signs suggesting an intraorbital foreign body.

PMID- 21085922
TI  - [Orbital and intracranial complications of acute sinusitis. Diagnostics and
      therapy in children and adolescents].
AB  - Orbital and intracranial complications of acute sinusitis occur more frequently
      in the pediatric population compared to adults due to anatomic differences. Since
      the introduction of antibiotics the frequency of such complications has been
      dramatically reduced. Nevertheless, even in the era of modern antibiotics these
      complications continue to occur and it is therefore of utmost importance not only
      to know about these complications but also to include them in the differential
      diagnosis. Appropriate diagnosis mainly based on CT scanning or magnetic
      resonance tomography is the basis for a rapid and sufficient and if necessary
      interdisciplinary treatment. In this CME article the diagnostic and therapeutic
      interventions in four young patients suffering from orbital or intracranial
      complications due to acute sinusitis are described and discussed in the context
      of the current literature and a clinical algorithm is introduced.

PMID- 21085924
TI  - The first ceratopsian dinosaur from South Korea.
AB  - In 2008, a new basal neoceratopsian was discovered in the Tando beds (Albian) of
      Tando Basin in South Korea. It represents the first ceratopsian dinosaur in the
      Korean peninsula and is assigned to Koreaceratops hwaseongensis gen. et sp. nov.
      Autapomorphies of Koreaceratops include very tall neural spines over five times
      higher than the associated centra in the distal caudals, and a unique astragalus
      divided into two fossae by a prominent craniocaudal ridge on the proximal
      surface. A phylogenetic analysis indicates that Koreaceratops is positioned
      between Archaeoceratops and all more derived neoceratopsians, and the elongation
      of caudal neural spines was an important derived character in non-ceratopsid
      neoceratopsians. The very tall caudal neural spines in Koreaceratops,
      Montanoceratops, Udanoceratops, Protoceratops, and Bagaceratops appear to be
      homoplasious, suggesting an independent adaptation, possibly for swimming.
      Skeletal evidence suggests that obligate quadrupedalism occurred gradually in
      neoceratopsians progressing from bipedal through facultative quadrupedalism, to
      complete quadrupedalism in Coronosauria.

PMID- 21085923
TI  - Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via
      epigenetic regulation.
AB  - Chemokines play important roles in asthma. Prostaglandin I(2) (PGI(2)) analogue
      is recently suggested as a candidate for treating asthma. However, the effects of
      PGI(2) analogues on the expression of Th1- and Th2-related chemokines are
      unknown. To this end, we investigated the in vitro effects of PGI(2) analogues on
      the expression of Th1-related chemokine interferon-gamma-inducible protein-10 (IP
      10/CXCL10) and Th2-related chemokine macrophage-derived chemokine (MDC/CCL22) in
      human monocytes. The human monocytes were pretreated with iloprost and
      treprostinil before lipopolysaccharide (LPS) stimulation. IP-10 and MDC were
      measured by ELISA. Intracellular signaling was investigated by cyclic adenosine
      monophosphate (cAMP) assay, western blot and chromatin immunoprecipitation.
      PGI(2) analogues enhanced MDC, but suppressed IP-10 expression in LPS-stimulated
      monocytes. These effects were reversed by the I prostanoid (IP) receptor
      antagonist (CAY10449), peroxisomal proliferators-activated receptor (PPAR)-alpha
      antagonist (GW6741) and PPAR-gamma antagonist (GW9662). PGI(2) analogues
      increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator,
      conferred similar effects. PGI(2) analogue-enhanced MDC expression was reduced by
      nuclear factor (NF) kappaB inhibitor (BAY 117085) and mitogen-activated protein
      kinase (MAPK)-p38 inhibitor (SB203580). PGI(2) analogues up-regulated phospho-p65
      and phospho-p38 but down-regulated phospho-ERK expression. Iloprost enhanced H3
      acetylation in MDC promoter area and suppressed H3 acetylation, H3K4, and H3K36
      trimethylation in IP-10 promoter area. PGI(2) analogues enhanced MDC expression
      via the I prostanoid-receptor-cAMP, PPAR-alpha and PPAR-gamma, NFkappaB-p65, MAPK
      p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10
      expression via the IP-receptor-cAMP, PPAR-gamma, MAPK-ERK-ELK1 pathways and
      inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes.
      PGI(2) analogues may therefore increase Th2 recruitment and inflammation.

PMID- 21085925
TI  - Biphasic activity of a jumping spider.
AB  - Individual variation is a ubiquitous and important factor that affects ecological
      dynamics. This study examined individual variation in the nest-use pattern of the
      jumping spider Phidippus audax. Although the jumping spider is a diurnal species,
      field observations in this study revealed that the majority of individuals
      remained in their nests during the day. An accompanying examination of the hunger
      level of the spiders revealed that spiders that remained in nests were more
      starved than those observed outside nests. If spiders actively forage when they
      are starved, as has been suggested by previous studies, one would expect to see
      the opposite trend (i.e., spiders that remained in nests are more satiated).
      Thus, the pattern observed in the field contradicts the known behavioral pattern
      of the spiders. An individual-based model was used to investigate the behavioral
      mechanism of the spider and the discrepancy found in the observations. A basic
      assumption of the model is that spiders possess distinct inactive and active
      phases (biphasic activity pattern), and transitions between the two phases are
      regulated by the hunger level of the spider. Data from a laboratory experiment
      were used to examine the assumptions of the model partially. The model was able
      to capture patterns observed in the data, suggesting that the pattern of
      transitions in biphasic activity is an important trait of the foraging behavior
      of the jumping spider.

PMID- 21085926
TI  - The effects of obesity and type 2 diabetes mellitus on cardiac structure and
      function in adolescents and young adults.
AB  - AIMS/HYPOTHESIS: We sought to evaluate the effects of obesity and obesity-related
      type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and
      diastolic function in adolescents and young adults. METHODS: Cardiac structure
      and function were compared by echocardiography in participants who were lean,
      obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study.
      Group differences were assessed using ANOVA. Independent determinants of cardiac
      outcome measures were evaluated with general linear models. RESULTS: Adolescents
      with obesity and obesity-related type 2 diabetes were found to have abnormal
      cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05).
      These two groups also had increased systolic function. Diastolic function
      decreased from the lean to obese to obese diabetic groups with the lowest
      diastolic function observed in the obese diabetic group (p < 0.05). Regression
      analysis showed that group, BMI z score (BMIz), group * BMIz interaction and
      systolic BP z score (BPz) were significant determinants of cardiac structure,
      while group, BMIz, systolic BPz, age and fasting glucose were significant
      determinants of the diastolic function (all p < 0.05).
      CONCLUSIONS/INTERPRETATION: Adolescents with obesity and obesity-related type 2
      diabetes demonstrate changes in cardiac geometry consistent with cardiac
      remodelling. These two groups also demonstrate decreased diastolic function
      compared with lean controls, with the greatest decrease observed in those with
      type 2 diabetes. Adults with diastolic dysfunction are known to be at increased
      risk of progressing to heart failure. Therefore, our findings suggest that
      adolescents with obesity-related type 2 diabetes may be at increased risk of
      progressing to early heart failure compared with their obese and lean
      counterparts.

PMID- 21085929
TI  - Clinical and radiographic outcomes of minimally invasive total knee arthroplasty
      through a lateral approach.
AB  - PURPOSE: With increasing confidence and surgical experience, minimally invasive
      surgery (MIS) in total knee arthroplasty (TKA) is now being applied to more
      complicated cases. The present study assessed the feasibility of MIS-TKA using a
      lateral approach for valgus knees. METHODS: Subjects comprised 26 patients with
      valgus knees who underwent MIS-TKA using a lateral subvastus approach. Five cases
      required a 1-cm snip of vastus lateralis obliquus, to shift the patella medially
      without eversion. Clinical scores and radiographic parameters of lateral MIS-TKA
      were examined and compared with those of 26 medial MIS-TKAs matched for
      preoperative patient characteristics. RESULTS: The lateral MIS-TKA group showed
      slightly longer operative time and larger skin incision than the medial MIS-TKA
      group. Nevertheless, myoglobin index and pain on a visual analog scale on
      postoperative day 7 were significantly lower in the lateral MIS-TKA group than in
      the medial MIS-TKA group. Postoperative improvement of clinical scores was quite
      comparable between lateral and medial MIS-TKA groups. Radiographic assessment
      revealed that tibiofemoral mechanical axis aligned within +/-3 degrees  from
      ideal in 24 of 26 patients after lateral MIS-TKA. MIS technique-related
      complications occurred in only 1 patient presenting with subsidence of the tibial
      component, due to malpositioning of the tibial component. CONCLUSION: From the
      perspectives of postoperative pain, clinical scores, radiographic accuracy, and
      postoperative complication rate, lateral MIS-TKA achieved comparable or superior
      results to medial MIS-TKA. This technique may offer a promising technical option
      that can be utilized for most patients with valgus knee deformity.

PMID- 21085930
TI  - Tendon-grasping strength of various suture configurations for rotator cuff
      repair.
AB  - PURPOSE: The purpose of the present study is to evaluate the mechanical
      performance and initial strength of the arthroscopic Mason-Allen, double
      mattress, inclined Mason-Allen, and lasso loop stitch configurations. METHODS:
      Using 36 sheep infraspinatus tendons, tendon widths and thicknesses were measured
      with a digital caliper to confirm standardization of the tendons. Four different
      stitch configurations (Mason-Allen, inclined Mason-Allen, double mattress, and
      lasso loop) were biomechanically tested with cyclic loading followed by load to
      failure testing. The cyclic elongation, peak-to-peak displacement, ultimate
      tensile strength, stiffness, and mode of failure were recorded. RESULTS: Mean
      tendon widths and thicknesses were statistically the same. The lasso loop (0.7 +/
      0.1 mm) demonstrated a mean cyclic elongation greater than the Mason-Allen (0.5
      +/- 0.3 mm) and double mattress (0.5 +/- 0.3 mm) groups (P = 0.011; P = 0.013).
      No differences were found in ultimate failure load, stiffness, and peak-to-peak
      displacement for the Mason-Allen (mean 99 +/- 42 N, 39 +/- 9 N/mm, 0.6 +/- 0,1
      mm), inclined Mason-Allen (113 +/- 52 N, 44 +/- 14 N/mm, 0.5 +/- 0.1 mm), double
      mattress stitch (119 +/- 68 N, 45 +/- 10 N/mm, 0.5 +/- 0.1 mm), or lasso loop
      (100 +/- 38 N, 42 +/- 7 N/mm, 0.5 +/- 0.1 mm) groups (n.s.). Each specimen failed
      at the suture-tendon interface. Three specimens (two Mason-Allen and one inclined
      Mason-Allen) failed during cyclic testing. CONCLUSION: Conventional Mason-Allen
      configuration can be applied with double-loaded suture anchor safely. Recent
      modifications of the configurations offer no biomechanical advantage.

PMID- 21085931
TI  - Patellofemoral kinematics in mobile-bearing and fixed-bearing posterior
      stabilised total knee replacements: a cadaveric study.
AB  - PURPOSE: The aim was to compare the patellar kinematics in the normal knee, fixed
      bearing (FB) and mobile-bearing total knee replacement (MB-TKR). The hypothesis
      that a mobile-bearing TKR has a more natural patellar movement was tested.
      METHODS: Computer navigation was used to track the patella in nine whole lower
      extremities in the natural knee and in the same knee with a posterior stabilised
      FB-TKR and a posterior stabilised MB-TKR from 0 degrees  to 90 degrees  flexion.
      The form and position of the trochlea in the natural knee and the patellar groove
      of the TKR femoral component was also analysed. RESULTS: There were no
      differences between the FB and MB-TKRs. But the patella in the TKRs at flexion
      angles of more than 50 degrees  had a more medial tilt compared to the natural
      knee. The patella of the natural knee tended to rotate externally with flexion,
      this was not seen in both TKR types. There were no significant differences in
      absolute mediolateral translation nor in translation relative to the patellar
      groove. During flexion, the patella lost contact with its groove earlier in the
      TKRs. The radius of the patellar groove of the femoral component was larger. The
      groove extended more superiorly and less far posteriorly, it was also positioned
      further laterally compared to the natural knee. CONCLUSIONS: There are subtle
      kinematic differences in patellar tracking between the natural knee and a TKR
      presumably due to differences in the shape and position of the patellar groove.
      There are no kinematic differences in patellar movement between the FB- and MB
      TKR.

PMID- 21085932
TI  - ACL graft re-rupture after double-bundle reconstruction: factors that influence
      the intra-articular pattern of injury.
AB  - PURPOSE: To determine the most common rupture patterns of previously
      reconstructed DB-ACL cases, seen at the time of revision surgery, and to
      determine the influence of age, gender, time between the initial ACL
      reconstruction and re-injury, tunnel angle and etiology of failure. METHODS:
      Forty patients who presented for revision surgery after previous double-bundle
      ACL reconstruction were enrolled. Three orthopedic surgeons independently
      reviewed the arthroscopic videos and determined the rupture pattern of both the
      anteromedial and posterolateral grafts. The graft rupture pattern was then
      correlated with the previously mentioned factors. RESULTS: The most common injury
      pattern seen at the time of revision ACL surgery was mid-substance AM and PL
      bundle rupture. Factors that influenced the rupture pattern (proximal vs. mid
      substance and distal rupture vs. elongated, but in continuity) were months
      between ACL reconstruction and re-injury (P = 0.002), the etiology of failure
      (traumatic vs. atraumatic) (P = 0.025) and the measured graft tunnel angle (P =
      0.048). CONCLUSIONS: The most common pattern of graft re-rupture was mid
      substance AM and mid-substance PL. As the length of time from the initial DB-ACL
      reconstruction to revision surgery increased, the pattern of injury more closely
      resembled that of the native ACL. Evaluation of patients who have undergone
      double-bundle ACL reconstruction, with a particular focus on graft maturity,
      mechanism of injury and femoral tunnel angles, and graft rupture pattern assists
      in preoperative planning for revision surgery.

PMID- 21085934
TI  - Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of
      healthy postmenopausal women living at northerly latitudes: a major cause for
      concern?
AB  - We assessed sunlight and dietary contributions to vitamin D status in British
      postmenopausal women. Our true longitudinal 25-hydroxyvitamin D (25(OH)D)
      measurements varied seasonally, being lower in the north compared to the south
      and lower in Asian women. Sunlight exposure in summer and spring provided 80%
      total annual intake of vitamin D. INTRODUCTION: Vitamin D deficiency is
      highlighted as a potential problem for countries at high latitude, but there are
      few true longitudinal, seasonal data to allow regional comparisons. We aimed to
      directly compare seasonal variation in vitamin D status (25(OH)D) in
      postmenopausal women at two northerly latitudes and to assess the relative
      contributions of sunlight exposure and diet. METHODS: Vitamin D status was
      assessed in 518 postmenopausal women (age 55-70 years) in a two-centre cohort
      study with serum collected at fixed three-monthly intervals from summer 2006 for
      immunoassay measurement of 25(OH)D and parathyroid hormone. At 57 degrees  N
      (Aberdeen, Scotland, UK), there were 338 Caucasian women; at 51 degrees  N
      (Surrey, South of England, UK), there were 144 Caucasian women and 35 Asian
      women. UVB exposure (polysulphone film badges) and dietary vitamin D intakes
      (food diaries) were also estimated. RESULTS: Caucasian women had lower 25(OH)D (p
      < 0.001) at 57 degrees  N compared to 51 degrees  N. Median (interquartile range)
      in nanomoles per litre for summer (June-August) at 57 degrees  N was 43.0 (20.9)
      and at 51 degrees  N was 62.5 (26.6) and for winter (December-February) at 57
      degrees  N was 28.3 (18.9) and at 51 degrees  N was 39.9 (24.0). For Asian women
      at 51 degrees  N, median 25(OH)D was 24.0 (15.8) nmol/L in summer and 16.9 (15.9)
      nmol/L in winter. Median dietary vitamin D intakes were 80-100 IU for Caucasians
      and 50-65 IU for the Asian women. Sunlight was the main contributor to 25(OH)D
      with spring and summer providing >80% total annual intake. CONCLUSIONS: These
      longitudinal data show significant regional and ethnic differences in UVB
      exposure and vitamin D status for postmenopausal women at northerly latitudes.
      The numbers of women who are vitamin D deficient is a major concern and public
      health problem.

PMID- 21085936
TI  - Quinolones control in milk and eggs samples by liquid chromatography using a
      surfactant-mediated mobile phase.
AB  - Four quinolones (danofloxacin, difloxacin, flumequine and marbofloxacin) were
      determined in milk and egg samples by a simplified high-performance liquid
      chromatographic procedure using a micellar mobile phase. No extraction was needed
      to precipitate the proteins from the matrices since they were solubilised in
      micelles. The only pretreatment steps required were homogenisation, dilution and
      filtration before injecting the sample into the chromatographic system. An
      adequate resolution of the quinolones was achieved by a chemometrics approach
      where retention was modelled as a first step using the retention factors in only
      five mobile phases. Afterwards, an optimisation criterion was applied to consider
      the position and shape of the chromatographic peaks. Analytical separation
      involved a C18 reversed-phase column, a hybrid micellar mobile phase of 0.05 M
      sodium dodecyl sulphate, 10% (v/v) butanol and 0.5% (v/v) triethylamine buffered
      at pH 3 and fluorimetric detection. Quinolones were eluted in less than 15 min
      without the protein band or other endogenous compounds from the food matrices
      interfering. The calculated relevant validation parameters, e.g., decision limit
      (CC(alpha)), detection capability (CC(beta)), repeatability, within-laboratory
      reproducibility, recoveries and robustness, were acceptable and complied with
      European Commission Decision 2002/657/EC. Finally, the proposed method was
      successfully employed in quantifying the four quinolones in spiked egg and milk
      samples.

PMID- 21085933
TI  - We do not have evidence based methods for the treatment of cartilage defects in
      the knee.
AB  - PURPOSE: The aim of this study was to perform a systematic review of studies
      concerning current treatment of chondral defects of the knee. METHODS: The
      relevance for evidence based data and for successful surgical treatment of
      cartilage defects was evaluated. From 56,098 evaluated studies, 133 studies could
      be further pursued. These supplied data concerning microfracturing, the
      osteochondral autograft transplantation system (OATS), the autologous chondrocyte
      implantation (ACI) and the matrix induced chondrocyte implantation (MACI). The
      modified Coleman Methodical Score (CMS) and the Level of Evidence (LOE) were
      applied to evaluate the quality. RESULTS: In these studies, a total of 6,920
      patients were reviewed with a median of 32 patients per study and a mean follow
      up of 24 months. The mean CMS was 58 of 100 points. No study reached 100 points
      in the CMS. Three studies reached a level above 90. Ten studies were Level I,
      five studies reached Level II. Seven studies reached Level III, 111 studies Level
      IV. MRI scans to verify the clinical data were used by only 72 studies. The means
      in the modified CMS were for the different procedures as follows: ACI 58 points,
      MACI 57 points, microfracturing 68 points and OATS 50 points. 24 studies applied
      the Lysholm Score (LS) for clinical evaluation of cartilage surgery. All
      operative procedures yielded comparable improvements of the LS (n.s.) meaning
      that no operative procedure proved superior. CONCLUSION: As the majority of
      studies evaluated by this review is insufficient for EBM purposes more coherent
      studies with LOE of I or II are needed. Co-relating the systems of CMS and LOE
      and validating the applied scores seems desirable.

PMID- 21085935
TI  - Subtrochanteric fractures after long-term treatment with bisphosphonates: a
      European Society on Clinical and Economic Aspects of Osteoporosis and
      Osteoarthritis, and International Osteoporosis Foundation Working Group Report.
AB  - This paper reviews the evidence for an association between atypical
      subtrochanteric fractures and long-term bisphosphonate use. Clinical case
      reports/reviews and case-control studies report this association, but
      retrospective phase III trial analyses show no increased risk. Bisphosphonate use
      may be associated with atypical subtrochanteric fractures, but the case is yet
      unproven. INTRODUCTION: A Working Group of the European Society on Clinical and
      Economic Aspects of Osteoporosis and Osteoarthritis and the International
      Osteoporosis Foundation has reviewed the evidence for a causal association
      between subtrochanteric fractures and long-term treatment with bisphosphonates,
      with the aim of identifying areas for further research and providing
      recommendations for physicians. METHODS: A PubMed search of literature from 1994
      to May 2010 was performed using key search terms, and articles pertinent to
      subtrochanteric fractures following bisphosphonate use were analysed. RESULTS:
      Several clinical case reports and case reviews report a possible association
      between atypical fractures at the subtrochanteric region of the femur in
      bisphosphonate-treated patients. Common features of these 'atypical' fractures
      include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal
      cortex and transverse fracture pattern. Some small case-control studies report
      the same association, but a large register-based study and retrospective analyses
      of phase III trials of bisphosphonates do not show an increased risk of
      subtrochanteric fractures with bisphosphonate use. The number of atypical
      subtrochanteric fractures in association with bisphosphonates is an estimated one
      per 1,000 per year. It is recommended that physicians remain vigilant in
      assessing their patients treated with bisphosphonates for the treatment or
      prevention of osteoporosis and advise patients of the potential risks.
      CONCLUSIONS: Bisphosphonate use may be associated with atypical subtrochanteric
      fractures, but the case is unproven and requires further research. Were the case
      to be proven, the risk-benefit ratio still remains favourable for use of
      bisphosphonates to prevent fractures.

PMID- 21085937
TI  - Endpoints in paediatric oncology.
AB  - PURPOSE: The purpose of this review is to address the issue of endpoints in
      paediatric oncology. Oncologists use this term to refer to an outcome they are
      trying to measure with a clinical trial, which may become accordingly the object
      of scientific articles. The outcome measured may concern both efficacy and
      safety, although from different perspectives. METHODS: Based on both literature
      and experience developed in clinical trials, the different types of endpoints
      have been critically analysed in their power to provide the highest information
      of therapeutic interest (efficacy and safety) with the least risk and discomfort
      for the individual. Primary, secondary and surrogate endpoints have been
      distinguished. The most relevant differences have been discussed in comparison
      with adult oncology settings of endpoints. RESULTS: The rarity of cancer in
      childhood and adolescence and the objective difficulty of enrolling statistically
      conceivable numbers of individuals have determined the utmost positive
      development of large scale, multinational clinical trials. The most interesting
      consequence is that the impact of multiplicity interferences, which is usually
      present in virtually all clinical trials developed for adults with cancer, is not
      a common event in paediatric oncology. Nevertheless, many of the questions
      concerning the different impact on outcome and survival of clinical trials
      developed in adult oncology remain unanswered due to the objective limitations
      still existing in terms of cure compared with paediatric oncology. The powerful
      consistency of cure rate, as the most relevant endpoint of clinical trials
      developed in paediatric oncology, addresses additional considerations to support
      the relevant differences existing between adult and paediatric oncology: both the
      development of clinical trials with different aims (confirmatory versus primary
      response) and the limited impact of multiplicity limitations may determine
      different implications regarding the meaning of endpoints in paediatric and adult
      oncology. CONCLUSION: The aim of cancer treatment is to improve survival (SUR)
      and quality of life (QoL), but some restraints on the conduct of clinical trials
      may make these goals unattainable. Clinical trial endpoints represent a measure
      method aimed to grant answers to questions addressed by the clinical trial
      itself. The effect of the new regulation is expected to stimulate high-quality
      research and provide robust information on paediatric drugs to increase the
      availability of such drugs to children.

PMID- 21085938
TI  - Clinical research in newborn infants: difficulties and specificity.
AB  - BACKGROUND: Clinical trials are essential in neonates to evaluate scientifically
      the efficacy and safety of drugs. However, major specificities condition clinical
      research in human neonates. OBJECTIVE: To review specific constraints to be taken
      into account in neonatal research studies. METHODS: A review of the literature
      and contribution of authors' opinions was carried out. RESULTS AND CONCLUSION:
      Neonatal specificities that induce obstacles in neonatal studies and proposals
      are detailed. This review also looks at recommendations recently developed by the
      European Commission to promote safe and ethical research in neonatology.

PMID- 21085939
TI  - Infection by Trypanosoma cruzi enhances anion conductance in rat neonatal
      ventricular cardiomyocytes.
AB  - Recent studies on malaria-infected erythrocytes have shown increased anion
      channel activity in the host cell membrane, increasing the exchange of solutes
      between the cytoplasm and exterior. In the present work, we addressed the
      question of whether another intracellular protozoan parasite, Trypanosoma cruzi,
      alters membrane transport systems in the host cardiac cell. Neonatal rat
      cardiomyocytes were cultured and infected with T. cruzi in vitro. Ion currents
      were measured by patch-clamp technique in the whole-cell configuration. Two small
      magnitude instantaneous anion currents, outward- and inward-rectifying, were
      recorded in all noninfected cardiomyocytes. In addition, ~10% of cardiomyocytes
      expressed a large anion-preferable, time-dependent current activated at positive
      membrane potentials. Hypotonic (230 mOsm) treatment resulted in the disappearance
      of the time-dependent current but provoked a dramatic increase of the
      instantaneous outward-rectifying one. Both instantaneous currents were suppressed
      by intracellular Mg(2+). T. cruzi infection did not provoke new anion currents in
      the host cells but caused an increase of the density of intrinsic swelling
      activated outward current, up to twice in heavily infected cells. The occurrence
      of a time-dependent current dramatically increased in infected cells in the
      presence of Mg(2+) in the intracellular solution, from ~10 to ~80%, without a
      significant change of the current density. Our findings represent one further,
      besides the known Plasmodium falciparum, example of an intracellular parasite
      which upregulates the anionic currents expressed in the host cell.

PMID- 21085941
TI  - Response to "resolution of dyssynchronous left ventricular failure via cardiac
      resynchronization and subsequent radiofrequency ablation in an infant with
      preexcitation".

PMID- 21085942
TI  - Concomitant one-stage unifocalization and bidirectional Glenn procedure.
AB  - A concomitant one-stage unifocalization and bidirectional Glenn procedure was
      performed in a patient with a functionally single ventricle, pulmonary atresia,
      and major aortopulmonary collateral arteries (MAPCAs). Reconstruction of the
      absent central pulmonary artery was achieved using the MAPCAs as well as the
      autologous pericardium. After 1 year, cineangiography and cardiac catheterization
      showed an excellent result: well-developed pulmonary arteries as well as low
      pressure in the superior vena cava. To the best of our knowledge, this is the
      first report of a successful concomitant one-stage unifocalization and
      bidirectional Glenn procedure.

PMID- 21085940
TI  - Amphotericin B membrane action: role for two types of ion channels in eliciting
      cell survival and lethal effects.
AB  - The formation of aqueous pores by the polyene antibiotic amphotericin B (AmB) is
      at the basis of its fungicidal and leishmanicidal action. However, other types of
      nonlethal and dose-dependent biphasic effects that have been associated with the
      AmB action in different cells, including a variety of survival responses, are
      difficult to reconcile with the formation of a unique type of ion channel by the
      antibiotic. In this respect, there is increasing evidence indicating that AmB
      forms nonaqueous (cation-selective) channels at concentrations below the
      threshold at which aqueous pores are formed. The main foci of this review will be
      (1) to provide a summary of the evidence supporting the formation of cation
      selective ion channels and aqueous pores by AmB in lipid membrane models and in
      the membranes of eukaryotic cells; (2) to discuss the influence of membrane
      parameters such as thickness fluctuations, the type of sterol present and the
      existence of sterol-rich specialized lipid raft microdomains in the formation
      process of such channels; and (3) to develop a cell model that serves as a
      framework for understanding how the intracellular K(+) and Na(+) concentration
      changes induced by the cation-selective AmB channels enhance multiple survival
      response pathways before they are overcome by the more sustained ion fluxes,
      Ca(2+)-dependent apoptotic events and cell lysis effects that are associated with
      the formation of AmB aqueous pores.

PMID- 21085943
TI  - Clinical spectrum in a family with tropomyosin-mediated hypertrophic
      cardiomyopathy and sudden death in childhood.
AB  - This report demonstrates variable clinical courses in several members of a family
      with tropomyosin-mediated hypertrophic cardiomyopathy (HCM) (L185R mutation). The
      index case was an 8-year-old girl who died from sudden cardiac death and was
      diagnosed with HCM on autopsy. Her father had minimal hypertrophy but had an
      implantable cardioverter defibrillator placed prophylactically with no
      appropriate shocks. Two brothers progressed from normal phenotype to HCM on
      follow-up, the younger with significant hypertrophy and the older with mild
      hypertrophy. They both had malignant arrhythmia courses with VF, which was
      terminated by ICD shock. In conclusion, family members with same genotype can
      have significantly variable phenotypes.

PMID- 21085944
TI  - Tetralogy of fallot with restrictive ventricular septal defect.
AB  - We present a case of tetralogy of Fallot with progressive restriction of the
      ventricular septal defect (VSD) by tricuspid valve tissue. The report includes
      echocardiographic and catheter images of this rare complication of tetralogy of
      Fallot. Restriction of the VSD in tetralogy of Fallot is associated with
      increased surgical-related mortality.

PMID- 21085945
TI  - Low renal oximetry correlates with acute kidney injury after infant cardiac
      surgery.
AB  - Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass
      surgery during infancy. Standard methods for evaluating renal function are not
      particularly sensitive nor are proximate indicators of renal dysfunction that
      allow intervention in real time. Near-infrared spectroscopy (NIRS) is a newer
      noninvasive technology that continuously evaluates regional oximetry and may
      correlate with renal injury and adverse outcomes after cardiac surgery in
      infants. This prospective observational study enrolled 40 infants (age, <12
      months) undergoing biventricular repair. Continuous renal oximetry data were
      collected for the first 48 postoperative hours and correlated with postoperative
      course, standard laboratory data, and the occurrence of acute renal injury.
      Subjects with low renal oximetry (below 50% for >2 h) had significantly higher
      postoperative peak creatinine levels by 48 h (0.8 +/- 0.4 vs. 0.52 +/- 0.2; p =
      0.003) and a higher incidence of AKI (50 vs. 3.1%; p = 0.003) than those with
      normal renal oximetry. These subjects also required more ventilator days and
      greater vasoactive support, and they had elevated lactate levels. Prolonged low
      renal near-infrared oximetry appears to correlate with renal dysfunction,
      decreased systemic oxygen delivery, and the overall postoperative course in
      infants with congenital heart disease undergoing biventricular repair.

PMID- 21085946
TI  - Interactions between the yeast Ogataea pini and filamentous fungi associated with
      the western pine beetle.
AB  - Ecologically important microbes other than filamentous fungi can be housed within
      the fungal-transport structures (mycangia) of Dendroctonus bark beetles. The
      yeast Ogataea pini (Saccharomycetales: Saccharomycetaceae) was isolated from the
      mycangia of western pine beetle (Dendroctonus brevicomis) populations in northern
      Arizona (USA) with a frequency of 56%. We performed a series of in vitro assays
      to test whether volatile organic compounds produced by O. pini affected radial
      growth rates of mutualistic and antagonistic species of filamentous fungi that
      are commonly found in association with the beetle including Entomocorticium sp.
      B, Ophiostoma minus, Beauvaria bassiana, and an Aspergillus sp. We determined the
      compounds O. pini produced when grown on 2% malt extract agar using a gas
      chromatography/mass spectrometry (GC/MS) analysis of headspace volatiles.
      Volatiles produced by O. pini on artificial media significantly enhanced the
      growth of the mutualistic Entomocorticium sp. B, and inhibited growth of the
      entomopathogenic fungus B. bassiana. GC/MS revealed that O. pini produced
      ethanol, carbon disulfide (CS(2)), and Delta-3-carene in headspace. The results
      of these studies implicate O. pini as an important component in D. brevicomis
      community ecology, and we introduce multiple hypotheses for future tests of the
      effects of yeasts in the symbiont assemblages associated with Dendroctonus bark
      beetles.

PMID- 21085947
TI  - Site-specific recombination system based on actinophage TG1 integrase for gene
      integration into bacterial genomes.
AB  - Phage integrases are enzymes that catalyze unidirectional site-specific
      recombination between the attachment sites of phage and host bacteria, attP and
      attB, respectively. We recently developed an in vivo intra-molecular site
      specific recombination system based on actinophage TG1 serine-type integrase that
      efficiently acts between attP and attB on a single plasmid DNA in heterologous
      Escherichia coli cells. Here, we developed an in vivo inter-molecular site
      specific recombination system that efficiently acted between the att site on
      exogenous non-replicative plasmid DNA and the corresponding att site on
      endogenous plasmid or genomic DNA in E. coli cells, and the recombination
      efficiencies increased by a factor of ~10(1-3) in cells expressing TG1 integrase
      over those without. Moreover, integration of attB-containing incoming plasmid DNA
      into attP-inserted E. coli genome was more efficient than that of the reverse
      substrate configuration. Together with our previous result that purified TG1
      integrase functions efficiently without auxiliary host factors in vitro, these in
      vivo results indicate that TG1 integrase may be able to introduce attB-containing
      circular DNAs efficiently into attP-inserted genomes of many bacterial species in
      a site-specific and unidirectional manner. This system thus may be beneficial to
      genome engineering for a wide variety of bacterial species.

PMID- 21085948
TI  - Metabolism of glucose and xylose as single and mixed feed in Debaryomyces
      nepalensis NCYC 3413: production of industrially important metabolites.
AB  - Efficient conversion of hexose and pentose (glucose and xylose) by a single
      strain is a very important factor for the production of industrially important
      metabolites using lignocellulose as the substrate. The kinetics of growth and
      polyol production by Debaryomyces nepalensis NCYC 3413 was studied under single
      and mixed substrate conditions. In the presence of glucose, the strain produced
      ethanol (35.8 +/- 2.3 g/l), glycerol (9.0 +/- 0.2 g/l), and arabitol (6.3 +/- 0.2
      g/l). In the presence of xylose, the strain produced xylitol (38 +/- 1.8 g/l) and
      glycerol (18 +/- 1.0 g/l) as major metabolites. Diauxic growth was observed when
      the strain was grown with different combinations of glucose/xylose, and glucose
      was the preferred substrate. The presence of glucose enhanced the conversion of
      xylose to xylitol. By feeding a mixture of glucose at 100 g/l and xylose at 100
      g/l, it was found that the strain produced a maximum of 72 +/- 3 g/l of xylitol.
      A study of important enzymes involved in the synthesis of xylitol (xylose
      reductase (XR) and xylitol dehydrogenase (XDH)), glycerol (glycerol-3-phosphate
      dehydrogenase (G3PDH)) and ethanol (alcohol dehydrogenase (ADH)) in cells grown
      in the presence of glucose and xylose revealed high specific activity of G3PDH
      and ADH in cells grown in the presence of glucose, whereas high specific activity
      of XR, XDH, and G3PDH was observed in cells grown in the presence of xylose. To
      our knowledge, this is the first study to elaborate the glucose and xylose
      metabolic pathway in this yeast strain.

PMID- 21085949
TI  - Protection of mice against enterotoxigenic E. coli by immunization with a
      polyvalent enterotoxin comprising a combination of LTB, STa, and STb.
AB  - Currently available enterotoxigenic Escherichia coli (ETEC) vaccines are based on
      colonization factors and/or the heat-labile enterotoxin B subunit (LTB). However,
      the induction of antitoxic responses against heat-stable enterotoxin a (STa) and
      b (STb) has merit as these two poorly immunogenic toxins are frequently
      associated with ETEC strains. In this study, we genetically constructed a
      trivalent enterotoxin fusion protein (STa-LTB-STb, abbreviated to SLS) in an
      effort to develop a single toxoid containing these three enterotoxins for
      vaccination against ETEC. Mutagenesis at one disulfide-bridge-forming cysteine in
      STa led to a dramatic reduction in the STa toxicity of SLS; however, the fusion
      peptide retained the STb-associated toxicity. Immunization of mice with SLS
      protein elicited significant antibody responses to LTB, STa, and STb.
      Significantly, the mice antisera were able to neutralize the biological activity
      of both STa and STb. In the experiment to assess the protective effect of SLS
      immunization, the mortality of mice receiving SLS was significantly lower than
      their control cohorts (P < 0.01) after intraperitoneal challenge with ETEC. These
      results show that the trivalent fusion enterotoxin SLS has the potential to serve
      as a useful toxin-based vaccine against ETEC-induced diarrheal disease via a
      single immunogen.

PMID- 21085950
TI  - Lytic enzyme discovery through multigenomic sequence analysis in Clostridium
      perfringens.
AB  - With their ability to lyse Gram-positive bacteria, phage lytic enzymes (or
      lysins) have received a great deal of attention as novel anti-infective agents.
      The number of known genes encoding these peptidoglycan hydrolases has increased
      markedly in recent years, due in large part to advances in DNA sequencing
      technology. As the genomes of more and more bacterial species/strains are
      sequenced, lysin-encoding open reading frames (ORFs) can be readily identified in
      lysogenized prophage regions. In the current study, we sought to assess lysin
      diversity for the medically relevant pathogen Clostridium perfringens. The
      sequenced genomes of nine C. perfringens strains were computationally mined for
      prophage lysins and lysin-like ORFs, revealing several dozen proteins of various
      enzymatic classes. Of these lysins, a muramidase from strain ATCC 13124 (termed
      PlyCM) was chosen for recombinant analysis based on its dissimilarity to
      previously characterized C. perfringens lysins. Following expression and
      purification, various biochemical properties of PlyCM were determined in vitro,
      including pH/salt-dependence and temperature stability. The enzyme exhibited
      activity at low MUg/ml concentrations, a typical value for phage lysins. It was
      active against 23 of 24 strains of C. perfringens tested, with virtually no
      activity against other clostridial or non-clostridial species. Overall, PlyCM
      shows potential for development as an enzybiotic agent, demonstrating how
      expanding genomic databases can serve as rich pools for biotechnologically
      relevant proteins.

PMID- 21085952
TI  - Cloning, sequencing, and overexpression in Escherichia coli of the Enterobacter
      sp. Px6-4 gene for ferulic acid decarboxylase.
AB  - Ferulic acid decarboxylase (FADase) can catalyze the transformation of ferulic
      acid into 4-vinyl guaiacol via decarboxylation in microorganisms. In this study,
      a gene encoding FADase was first isolated from the bacterium Enterobacter sp. Px6
      4 using degenerate primers and a genome walking technique. The putative encoding
      gene (fad) of FADase consists of 507-bp nucleotides, coding a polypeptide of 168
      amino acid residues. In addition, a putative gene encoding the transcriptional
      regulator was identified from the upstream of the fad gene. The deduced peptide
      sequence of the FADase from Enterobacter sp. Px6-4 showed a 51.2-53.3% sequence
      identity to decarboxylases from other bacteria. The gene fad was successfully
      expressed in Escherichia coli BL21, and the recombinant FADase was purified as a
      protein of ca. 23 kDa with an optimal activity at pH 4.0 and 28  degrees C. The
      purified FADase could convert ferulic acid to 4-vinyl guaiacol effectively, and
      its hydrolytic activity could be inhibited by Cu(2+) (99%) and Hg(2+) (99.5%). A
      phylogenetic analysis of the FADase protein from bacteria revealed several
      different clades. Our result provided a basis for further studies of the ferulic
      acid transformation pathway and for enhanced production of vanillin in the
      future.

PMID- 21085951
TI  - Metallic copper corrosion rates, moisture content, and growth medium influence
      survival of copper ion-resistant bacteria.
AB  - The rapid killing of various bacteria in contact with metallic copper is thought
      to be influenced by the influx of copper ions into the cells, but the exact
      mechanism is not fully understood. This study showed that the kinetics of contact
      killing of copper surfaces depended greatly on the amount of moisture present,
      copper content of alloys, type of medium used, and type of bacteria. We examined
      antibiotic- and copper ion-resistant strains of Escherichia coli and Enterococcus
      faecium isolated from pig farms following the use of copper sulfate as feed
      supplement. The results showed rapid killing of both copper ion-resistant E. coli
      and E. faecium strains when samples in rich medium were spread in a thin, moist
      layer on copper alloys with 85% or greater copper content. E. coli strains were
      rapidly killed under dry conditions, while E. faecium strains were less affected.
      Electroplated copper surface corrosion rates were determined from electrochemical
      polarization tests using the Stern-Geary method and revealed decreased corrosion
      rates with benzotriazole and thermal oxide coating. Copper ion-resistant E. coli
      and E. faecium cells suspended in 0.8% NaCl showed prolonged survival rates on
      electroplated copper surfaces with benzotriazole coating and thermal oxide
      coating compared to surfaces without anti-corrosion treatment. Control of surface
      corrosion affected the level of copper ion influx into bacterial cells, which
      contributed directly to bacterial killing.

PMID- 21085953
TI  - Diagnostic 131I whole-body scintigraphy 1 year after thyroablative therapy in
      patients with differentiated thyroid cancer: correlation of results to the
      individual risk profile and long-term follow-up.
AB  - PURPOSE: (131)I whole-body scan (WBS) and serum thyroglobulin (TG) are important
      in detecting thyroid remnants or recurrent disease in patients with
      differentiated thyroid cancer. Usually, a diagnostic WBS is carried out 6 months
      after ablation to exclude residual disease. We retrospectively analysed results
      of a second routine diagnostic WBS and TG measurements at 1 year after
      thyroablation and correlated these to the risk profile of patients with long-term
      follow-up. METHODS: A total of 197 patients were followed up after thyroidectomy
      and ablative (131)I therapy. Follow-up included clinical examination, radioiodine
      WBS and thyroid-stimulating hormone (TSH), free thyroxine and TG measurements at
      3-6 months and 1 year after ablation. WBS (+) patients received a therapeutic
      activity of (131)I. The risk profile of patients was defined according to
      clinical results before the 1-year control. Clinical results at 1 year after
      ablation were analysed in correlation to the patient risk profile and long-term
      follow-up data (mean 7.2 years). RESULTS: One year after thyroablation, 95.8% of
      low-risk patients had no residual disease when diagnostic WBS was carried out
      using 370 MBq (131)I; 4.2% of low-risk patients had residual disease at this time
      point. In the high-risk group of this cohort, 54.5% were disease-free 1 year
      after ablation, but 45.5% demonstrated residual disease. After the 1-year
      control, 94% of all applied radioiodine therapies were executed in the high-risk
      group, compared with 6% in the low-risk group (p < 0.01). CONCLUSION: A second
      routine WBS 1 year after thyroablation is not indicated in low-risk patients.
      Risk stratification according to the early clinical course effectively identified
      patients with higher likelihood of persistent or recurrent disease in the long
      term follow-up.

PMID- 21085954
TI  - Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator
      protein in human brain using positron emission tomography.
AB  - PURPOSE: Translocator protein (TSPO) is a promising biomarker for
      neuroinflammation. We developed two new PET ligands, (18)F-PBR06 and (11)C-PBR28,
      to image TSPOs. Although our prior studies suggest that either of the two ligands
      could be used to quantify TSPOs in human brain, the studies were done in
      different sets of subjects. In this study, we directly compared (18)F-PBR06 and
      (11)C-PBR28 in eight human subjects to determine (1) whether either ligand
      provides more precise measurements of TSPOs and (2) whether the higher in vitro
      affinity of PBR06 compared to PBR28 led to higher in vivo binding of (18)F-PBR06
      compared to (11)C-PBR28. METHODS: In vivo binding was calculated as total
      distribution volume (V(T)), using an unconstrained two-tissue compartment model.
      V(T) was corrected for plasma free fraction (f (P)) to measure ligand binding
      based on free ligand concentration in brain. RESULTS: Both ligands measured V(T)
      with similar precision, as evidenced by similarly good identifiability. However,
      V(T) for both radioligands increased with increasing lengths of data acquisition,
      consistent with the accumulation of radiometabolites in brain. Despite its higher
      lipophilicity and higher in vitro affinity, V(T)/f(P) of (18)F-PBR06 was similar
      to that of (11)C-PBR28. CONCLUSION: Both (18)F-PBR06 and (11)C-PBR28 are similar
      in terms of precision, sensitivity to accumulation of radiometabolites, and
      magnitude of in vivo binding. Thus, selection between the two radioligands will
      be primarily determined by the logistical impact of the different half-lives of
      the two radionuclides (110 vs 20 min).

PMID- 21085955
TI  - Blue rubber bleb nevus syndrome: imaging of small bowel lesions with peroral CT
      enterography.
AB  - Blue rubber bleb nevus syndrome (BRBNS) is a rare entity that consists of
      multiple venous malformations involving several organ systems, particularly the
      skin and the gastrointestinal tract. The diagnosis is based on clinical findings;
      however, imaging is required to investigate the extent of involvement and
      complications. A 17-year-old patient, with multiple blue skin nevus, was admitted
      to the emergency room of our hospital with severe gastrointestinal bleeding and
      melena. Upper endoscopy showed two wine-color vascular lesions in the duodenum,
      and colonoscopy revealed multiple lesions in the colon. Peroral CT enterography
      demonstrated multiple (more than 30) contrast-enhanced polypoid small bowel
      lesions, ranging in size from 5 to 16 mm. Some lesions contained millimetric
      calcifications representing phleboliths. The patient also had three pancreatic
      lesions which showed homogenous enhancement on the delayed images. Our findings
      show that peroral CT enterography is useful to demonstrate the extent of small
      bowel lesions of BRBNS. This is the first report of pancreatic involvement of
      BRBNS.

PMID- 21085956
TI  - Proximal humerus reconstruction after tumour resection: biological versus
      endoprosthetic reconstruction.
AB  - The purpose of this study was to compare the outcome, complications and survival
      of the three most commonly used surgical reconstructions of the proximal humerus
      after transarticular tumour resection. Between 1985 and 2005, 38 consecutive
      proximal humeral reconstructions using allograft-prosthesis composite (n = 10),
      osteoarticular allograft (n = 13) or a modular tumour prosthesis (n = 14) were
      performed in our clinic. The mean follow-up was ten years (1-25). Of these, 27
      were disease free at latest follow-up (mean 16.8 years) and ten had died of
      disease. The endoprosthetic group presented the smallest complication rate of 21%
      (n =1), compared to 40% (n = 4) in the allograft-prosthesis composite and 62% (n
      = 8) in the osteoarticular allograft group. Only one revision was performed in
      the endoprosthetic group, in a case of shoulder instability. Infection after
      revision (n = 3), pseudoarthrosis (n = 2), fracture of the allograft (n = 3) and
      shoulder instability (n = 4) were the major complications of allograft use in
      general. Kaplan-Meier analysis showed a significantly better implant survival for
      the endoprosthetic group (log-rank p = 0.002). At final follow-up the
      Musculoskeletal Tumour Society scores were an average of 72% for the allograft
      prosthetic composite (n = 7, median follow-up 17 years), 76% for the
      osteoarticular allograft (n = 3, 19 years) and 77% for the endoprosthetic
      reconstruction (n = 10, 5 years) groups. An endoprosthetic reconstruction after
      transarticular proximal humeral resection resulted in the lowest complication
      rate, highest implant survival and comparable functional results when compared to
      allograft-prosthesis composite and osteoarticular allograft use. We believe that
      the surgical approach that best preserves the abductor mechanism and provides
      sufficient surgical exposure for tumour resection contributed to better
      functional results and glenohumeral stability in the endoprosthetic group.

PMID- 21085958
TI  - Metal combs used for hair separation in scalp surgery.

PMID- 21085959
TI  - Retraction. Erratum to: Combined interventional and surgical treatment for acute
      aortic type A dissection.

PMID- 21085957
TI  - Infection in total hip replacement: meta-analysis.
AB  - While total hip arthroplasty has progressed to become one of the most successful
      surgical procedures ever developed, infection remains a serious complication. We
      have conducted a review of the literature pertaining to management of deep
      infection in total hip arthroplasty, specifically focusing on clinically relevant
      articles published in the last five years. A search was conducted using MEDLINE
      and PubMed, as well as a review of the Cochrane database, using the terms "total
      hip arthroplasty", "total hip replacement" and "infection". References for all
      selected articles were cross-checked. While the so-called two-stage revision is
      generally considered to be the gold standard for management, numerous studies now
      report outcomes for implant retention and reassessing one-stage revision
      strategies. There are encouraging reports for complex reconstruction options in
      patients with associated severe bone stock loss. The duration of antibiotic
      therapy remains controversial. There is concern about increasing bacterial
      resistance especially with the widespread use of vancomycin and ertapenem
      (carbapenem).

PMID- 21085960
TI  - Angiographic evaluation of feeding arteries of hepatocellular carcinoma in the
      caudate lobe of the liver.
AB  - PURPOSE: To evaluate the origins of feeders of hepatocellular carcinoma (HCC) in
      the caudate lobe (S1). MATERIALS AND METHODS: Eighty-eight HCCs (mean diameter
      21.4 mm) were treated by chemoembolization. The tumor-feeding caudate artery was
      confirmed when a tumor stain was demonstrated on angiogram and iodized oil was
      accumulated into the HCC and S1 on computed tomography (CT). The origins were
      divided into R(1) (right proximal), R(2) (right distal), L(1) (left proximal),
      L(2) (left distal), A (anterior segmental), P (posterior segmental), M (middle
      hepatic or medial segmental), Ph (proper hepatic), Ch (common hepatic), and Ex
      (extrahepatic). The origins of feeders supplying HCCs in the Spiegel lobe (SP; n
      = 36), the paracaval portion (PC; n = 38), and the caudate process (CP; n = 14)
      were also analyzed. RESULTS: One hundred sixteen feeders were identified: 11
      (9.5%) arose from R(1); 21 (18.1%) arose from R(2); nine arose (0.9%) from L(1);
      15 (12.9%) arose from L(2); 24 (20.7%) arose from A; 25 (21.6%) arose from P;
      seven (6.0%) arose from M; one (0.9%) arose from Ph; and three (2.6%) arose from
      Ex. HCCs in the SP and the PC were fed by feeders from both hepatic arteries (the
      ratios of right to left were 3:2 and 3:1, respectively), and HCCs in the CP were
      dominantly fed by feeders from the right hepatic artery. CONCLUSION: The caudate
      artery most frequently arises from the right hepatic artery, followed with almost
      equal frequency by the left hepatic, the anterior segmental, and the posterior
      segmental artery. The origins of the caudate arteries differ according to the
      subsegmental locations.

PMID- 21085961
TI  - Cryoplasty versus conventional angioplasty in femoropopliteal arterial
      recanalization: 3-year analysis of reintervention-free survival by treatment
      received.
AB  - PURPOSE: To compare long-term efficacy of cryoplasty therapy versus conventional
      angioplasty in the treatment of peripheral arterial atherosclerotic stenosis on
      the basis of our 3-year clinical experience. MATERIALS AND METHODS: From January
      2006 to December 2008, a total of 155 patients with 192 lesions of the
      femoropopliteal sector were randomized to receive either cryoplasty or
      conventional balloon angioplasty. The primary study end point was lesion target
      patency. Follow-up with clinical evaluation of patient's symptoms, ankle-brachial
      index, and Doppler ultrasound was scheduled at 1, 6, 9, 12, 24, and 36 months.
      RESULTS: For the cryoplasty group (n = 86), technical immediate success was
      achieved in 74.4% of lesions. Rate of significant dissection was 13.5% and rate
      of stent placement of 22%. In the long term, target lesion patency rate at 6
      months was 59.4%, with rates of 55.9, 52.6, and 49.1% at 1, 2, and 3 years,
      respectively. For the conventional angioplasty group (n = 69), the immediate
      technical success rate was 83.7%. Rate of significant dissection was 19%, and
      rate of stent placement was 72.9%. Patency rates at 6 months and at 1, 2, and 3
      years were 71.5, 61.2, 60, and 56%, respectively. CONCLUSION: Compared with
      conventional angioplasty, cryoplasty showed good immediate success rates with
      lower stent placement rates. During the 3-year follow-up, patency rates tended to
      equalize between the two modalities.

PMID- 21085963
TI  - Percutaneous cholecystostomy as a first-line therapy in chronic hemodialysis
      patients with acute cholecystitis with midterm follow-up.
AB  - PURPOSE: The purpose of this article was to share midterm results of percutaneous
      cholecystostomy (PC) as a first-line therapy in chronic hemodialysis patients
      with acute cholecystitis. METHODS: Fourteen chronic hemodialysis patients with
      acute cholecystitis underwent PC between March 2007 and May 2009 at our
      institute. On preoperative assessment, the patients were classified into the ASA
      score by the anesthesiology team. All patients were class IV because of severe
      underlying comorbidities. The patients were referred to interventional radiology
      unit for PC by consensus of the multidisciplinary team. RESULTS: The PC was
      technically successful in all the patients without minor or major complications
      related to the procedure. Clinical symptoms in three patients who presented with
      sepsis and multiorgan failure did not resolve after PC, and these patients died
      following urgent surgery, including open cholecystectomy and common bile duct
      exploration. A new cholecystitis attack was detected in one patient in the
      acalculous group at the sixth month of the follow-up period. The mean
      catheterization time was 31.7 (range, 28-41) days. The mean follow-up time was
      13.3 (range 4-21) months. CONCLUSIONS: The PC may come into consideration as a
      first-line treatment modality in the management of acute cholecystitis in poor
      surgical candidate chronic hemodialysis patients. This is the first report
      focusing on the midterm results of PC as a first-line therapy in hemodialysis
      patients with acute cholecystitis who could be operated on.

PMID- 21085962
TI  - Utility of MRI before and after uterine fibroid embolization: why to do it and
      what to look for.
AB  - The utility of magnetic resonance imaging (MRI) in the selection, procedure
      planning, and follow-up of patients undergoing arterial embolization for uterine
      fibroids is reviewed. Advantages of MRI over ultrasound include multiplanar
      imaging capability, a larger field of view, increased spatial resolution,
      improved anatomic detail, and the ability to detect other pelvic disorders. MRI
      can assess fibroid viability by detecting contrast agent enhancement. Magnetic
      resonance angiography has a useful role in evaluation of pelvic vasculature.
      Magnetic resonance parameters such as T1 and T2 relaxation times and diffusion
      weighted characteristics have an emerging role in predicting outcome before and
      after embolization. MRI may be used to evaluate technical success and to image
      potential complications after embolization.

PMID- 21085964
TI  - Intractable gastrointestinal bleeding from angiodysplasia in a patient with
      Bernard-Soulier syndrome.

PMID- 21085965
TI  - Preclinical pharmacokinetics, metabolism, and toxicity of azurin-p28 (NSC745104)
      a peptide inhibitor of p53 ubiquitination.
AB  - PURPOSE: Characterize the preclinical pharmacokinetics, metabolic profile, multi
      species toxicology, and antitumor efficacy of azurin-p28 (NSC 745104), an
      amphipathic, 28 amino acid fragment (aa 50-77) of the copper containing redox
      protein azurin that preferentially enters cancer cells and is currently under
      development for treatment of p53-positive solid tumors. METHODS: An LC/MS/MS
      assay was developed, validated, and applied to liver microsomes, serum, and tumor
      cells to assess cellular uptake and metabolic stability. Pharmacokinetics was
      established after administration of a single intravenous dose of p28 in
      preclinical species undergoing chronic toxicity testing. Antitumor efficacy was
      assessed on human tumor xenografts. A human therapeutic dose was predicted based
      on efficacy and pharmacokinetic parameters. RESULTS: p28 is stable, showed tumor
      penetration consistent with selective entry into tumor cells and significantly
      inhibited p53-positive tumor growth. Renal clearance, volume of distribution, and
      metabolic profile of p28 was relatively similar among species. p28 was non
      immunogenic and non-toxic in mice and non-human primates (NHP). The no observed
      adverse effect level (NOAEL) was 120 mg/kg iv in female mice. A NOAEL was not
      established for male mice due to decreased heart and thymus weights that was
      reversible and did not result in limiting toxicity. In contrast, the NOAEL for
      p28 in NHP was defined as the highest dose (120 mg/kg/dose; 1,440 mg/m(2)/dose)
      studied. The maximum-tolerated dose (MTD) for subchronic administration of p28 to
      mice is >240 mg/kg/dose (720 mg/m(2)/dose), while the MTD for subchronic
      administration of p28 to Cynomolgous sp. is >120 mg/kg (1,440 mg/m(2)/dose). The
      efficacious (murine) dose of p28 was 10 mg/kg ip per day. CONCLUSIONS: p28 does
      not exhibit preclinical immunogenicity or toxicity, has a similar metabolic
      profile among species, and is therapeutic in xenograft models.

PMID- 21085966
TI  - Thyroid autoimmunity may represent a predisposition for the development of
      fibromyalgia?
AB  - In our previous study, we observed that the presence of autoimmune thyroid
      disease worsens fibromyalgia (FM) symptoms. The aims of this study are to
      evaluate whether there is a predisposition for the development of FM in patients
      with Hashimoto's thyroiditis (HT) with or without subclinical hypothyroidism
      (SCH) and in patients with SCH alone and what is the weight of antithyroid
      antibody positivity and SCH on FM comorbidity. Fifty-two patients, 39 affected by
      HT with or without SCH and 13 by SCH, were matched with 37 patients affected by
      FM and 25 healthy subjects. Blood samples were collected from all study subjects
      for the determination of serum TSH, free triiodothyronine, free thyroxine,
      antithyroperoxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and non
      organ-specific autoantibodies. Clinical assessment of patients and controls
      included the "Fibromyalgia Impact Questionnaire" (FIQ), while pain severity was
      evaluated using a visual analogue scale (VAS). Patients and controls were also
      characterized by the presence of diffuse pain, fatigue, paresthesiae, muscle
      spasms, non-restful sleep, tension headache and presence of mood disorders. FM
      comorbidity resulted in twelve HT subjects (31%) and none in SCH patient. In
      particular, FM comorbidity in HT patients without SCH was 33.3% and in HT
      patients with SCH was 28.5%. Based on our data, we speculate that maybe there is
      more than a hypothesis regarding the cause-effect relation between thyroid
      autoimmunity and the presence of FM, thus suggesting a hypothetical role of
      thyroid autoimmunity in FM pathogenesis.

PMID- 21085967
TI  - Bilateral contrast-enhanced MR angiography of the hand: diagnostic image quality
      of accelerated MRI using echo sharing with interleaved stochastic trajectories
      (TWIST).
AB  - OBJECTIVES: To evaluate the image quality of time-resolved contrast-enhanced MRA
      (tr-MRA) employing echo-sharing with stochastic trajectories for the bilateral
      examination of the hands. METHODS: In this institutional review-board approved
      study, Tr-MRA was compared with multiphasic contrast-enhanced MRA (mp-MRA)
      featuring sub-systolic venous compression in 20 healthy volunteers at 3.0 T using
      the following settings: TR/TE: 2.8/1.2 ms, flip angle: 25 degrees , acceleration
      factor: 4, effective voxel size: 0.9 * 0.8 * 0.9 cm, acquisition time 4.9 s per
      3D volume. RESULTS: With tr-MRA the arterial first-pass contrast agent transit is
      clearly seen. On average the contrast agent arrived 34 s post-injection and
      reached the proper digital arteries after 44 s. The mean arterio-venous window
      was 13 s. Bilateral contrast enhancement was asynchronous in 56-62%. On a
      semiquantitative scale (0 = non-sufficient to 4 = excellent) tr-MRA (mp-MRA)
      yielded an average ranking of 2.8-3.6 (3.1-3.8) in the greater and intermediate
      sized segments and 1.3-2.0 (1.6-2.3) in the proper digital arteries. CONCLUSION:
      Compared with established multiphasic ce-MRA, time-resolved MRA allows a four
      times faster acquisition. It reflects the natural haemodynamics of the hand
      arteries with no need for sub-systolic venous compression and may be beneficial
      in the detection of hand circulation disorders. Image quality is comparable to mp
      MRA. In both techniques depiction of the proper digital arteries is limited.

PMID- 21085968
TI  - Radiation dose from volumetric helical perfusion CT of the thorax, abdomen or
      pelvis.
AB  - PURPOSE: To evaluate the radiation doses delivered during volumetric helical
      perfusion CT of the thorax, abdomen or pelvis. MATERIALS AND METHODS: The dose
      length product (DLP) and CT dose index (CTDIvol) were recorded and effective dose
      (E) determined for patients undergoing CT (4D adaptive spiral) for tumour
      evaluation. Image noise and contrast to noise (CNR) at peak enhancement were also
      assessed for quality. RESULTS: Forty two consecutive examinations were included:
      thorax (16), abdomen (10), pelvis (16). Z-axis coverage ranged from 11.4 to 15.7
      cm. Mean DLP was 1288.8 mGy.cm (range: 648 to 2456 mGy.cm). Mean CTDIvol was 96.2
      mGy (range: 32.3 to 169.4 mGy). Mean effective dose was 19.6 mSv (range: 12.3 mSv
      to 36.7 mSv). In comparison mean DLP and effective dose was 885.2 mGy.cm (range:
      504 to 1633 mGy.cm) and 13.3 mSV (range: 7.8 to 24.5 mSv) respectively for the
      standard staging CT thorax, abdomen and pelvis. Mean tumour CNR at peak
      enhancement was 1.87. CONCLUSION: The radiation dose imposed by perfusion CT was
      on average 1.5 times that of a CT thorax, abdomen and pelvis. The dose is not
      insubstantial, and must be balanced by the potential clinical utility of
      additional physiologic data. Further efforts towards dose reduction should be
      encouraged.

PMID- 21085969
TI  - Permeability properties and occludin expression in a primary cultured model gill
      epithelium from the stenohaline freshwater goldfish.
AB  - Techniques for the primary culture of fish gill epithelia on permeable supports
      have provided 'reconstructed' gill models appropriate for the study of gill
      permeability characteristics in vitro. Models developed thus far have been
      derived from euryhaline fish species that can tolerate a wide range of
      environmental salinity. This study reports on procedures for the primary culture
      of a model gill epithelium derived from goldfish, a stenohaline freshwater (FW)
      fish that cannot tolerate high environmental salt concentrations. The
      reconstructed goldfish gill epithelium was cultured on permeable filter inserts
      and using electron microscopy and immunocytochemical techniques, was determined
      to be composed exclusively of gill pavement cells. When cultured under
      symmetrical conditions (i.e. with culture medium bathing both apical and
      basolateral surfaces), epithelial preparations generated appreciable
      transepithelial resistance (TER) (e.g. 1,150 +/- 46 Omegacm(2)) within 36-42 h
      post-seeding in inserts. When apical medium was replaced with FW (asymmetrical
      conditions to mimic conditions that occur in vivo), epithelia exhibited increased
      TER and elevated paracellular permeability. Changes in permeability occurred in
      association with altered occludin-immunoreactive band position by western blot
      and no change in occludin mRNA abundance. We contend that the goldfish gill model
      will provide a useful in vitro tool for examining the molecular components of a
      stenohaline fish gill epithelium that participate in the regulation of gill
      permeability. The model will allow molecular observations to be made together
      with assessment of changing physiological properties that relate to permeability.
      Together, this will allow further insight into mechanisms that regulate gill
      permeability in fishes.

PMID- 21085970
TI  - Anoxic survival of the Pacific hagfish (Eptatretus stoutii).
AB  - It is not known how the Pacific hagfish (Eptatretus stoutii) can survive extended
      periods of anoxia. The present study used two experimental approaches to examine
      energy use during and following anoxic exposure periods of different durations
      (6, 24 and 36 h). By measuring oxygen consumption prior to anoxic exposure, we
      detected a circadian rhythm, with hagfish being active during night and showing a
      minimum routine oxygen consumption (RMR) during the daytime. By measuring the
      excess post-anoxic oxygen consumption (EPAOC) after 6 and 24 h it was possible to
      mathematically account for RMR being maintained even though heme stores of oxygen
      would have been depleted by the animal's metabolism during the first hours of
      anoxia. However, EPAOC after 36 h of anoxia could not account for RMR being
      maintained. Measurements of tissue glycogen disappearance and lactate appearance
      during anoxia showed that the degree of glycolysis and the timing of its
      activation varied among tissues. Yet, neither measurement could account for the
      RMR being maintained during even the 6-h anoxic period. Therefore, two
      independent analyses of the metabolic responses of hagfish to anoxia exposure
      suggest that hagfish utilize metabolic rate suppression as part of the strategy
      for longer-term anoxia survival.

PMID- 21085971
TI  - Identification of TCTE3 as a gene responsible for congenital diaphragmatic hernia
      using a high-resolution single-nucleotide polymorphism array.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm
      associated with pulmonary hypoplasia. Although genetic factors have been
      suggested to play a role, the etiology of CDH is still largely unknown. In this
      study, we analyzed copy number variants (CNVs) using a single-nucleotide
      polymorphism (SNP) array to examine whether microdeletions contribute to the
      pathogenesis of this disease. METHODS: A total of 28 CDH patients, including 24
      isolated and 4 non-isolated cases, were available. We performed CNV analysis
      using high-resolution SNP arrays (370K, 550K, 660K; Illumina Inc.) and CNstream
      software. Deletions in loci that have been suggested in previous studies to
      contain candidate genes affecting CDH were analyzed. RESULTS: We detected 335, 6
      and 133 deletions specific for patients in 14 (350K array), 3 (550K) and 11
      (660K) cases, respectively. Among these deletions, no segments included the
      previously suggested candidate genes with the exception of an 18-kb deletion
      observed in the candidate locus 6q27 in two non-isolated patients. This deleted
      region contains exon 4 of the t-complex-associated-testis-expressed 3 (TCTE3)
      gene. CONCLUSION: Because TCTE3 encodes a putative light chain of the outer
      dynein arm of cilia and human diseases caused by ciliary dysfunction show various
      phenotypes including skeletal defect, TCTE3 may be a genetic candidate
      influencing CDH.

PMID- 21085972
TI  - Skingineering I: engineering porcine dermo-epidermal skin analogues for
      autologous transplantation in a large animal model.
AB  - BACKGROUND: Extended full thickness skin defects still represent a considerable
      therapeutic challenge as ideal strategies for definitive autologous coverage are
      still not available. Tissue engineering of whole skin represents an equally
      attractive and ambitious novel approach. We have recently shown that laboratory
      grown human skin analogues with near normal skin anatomy can be successfully
      transplanted on immuno-incompetent rats. The goal of the present study was to
      engineer autologous porcine skin grafts for transplantation in a large animal
      model (pig study = intended preclinical study). MATERIALS AND METHODS: Skin
      biopsies were taken from the pig's abdomen. Epidermal keratinocytes and dermal
      fibroblasts were isolated and then expanded on culture dishes. Subsequently,
      highly concentrated collagen hydrogels and collagen/fibrin hydrogels
      respectively, both containing dermal fibroblasts, were prepared. Fibroblast
      survival, proliferation, and morphology were monitored using fluorescent
      labelling and laser scanning confocal microscopy. Finally, keratinocytes were
      seeded onto this dermal construct and allowed to proliferate. The resulting in
      vitro generated porcine skin substitutes were analysed by H&E staining and
      immunofluorescence. RESULTS: Dermal fibroblast proliferation and survival in pure
      collagen hydrogels was poor. Also, the cells were mainly round-shaped and they
      did not develop 3D-networks. In collagen/fibrin hydrogels, dermal fibroblast
      survival was significantly higher. The cells proliferated well, were spindle
      shaped, and formed 3D-networks. When these latter dermal constructs were seeded
      with keratinocytes, a multilayered and partly stratified epidermis readily
      developed. CONCLUSION: This study provides compelling evidence that pig cell
      derived skin analogues with near normal skin anatomy can be engineered in vitro.
      These tissue-engineered skin substitutes are needed to develop a large animal
      model to establish standardized autologous transplantation procedures for those
      studies that must be conducted before "skingineering" can eventually be
      clinically applied.

PMID- 21085973
TI  - Single payer health insurance in pediatric surgery: US impressions and Canadian
      experience.
AB  - CONTEXT: Some advocate single payer national health insurance, present in Canada,
      as a solution to problems in US health care. METHOD: Pediatric surgeons in the US
      and Canada were surveyed regarding their attitudes (US) and experience (Canada)
      under a single payer by electronic mail regarding features of a single payer
      using a Likert scale (1-strongly disagree to 5-strongly agree) on quality,
      administration, organization, and economics. RESULTS: Overall response rate of
      22% (175/835), 153 US, 22 Canadian. US and Canadian respondents predicted a
      higher quality of care for both emergency (66 and 36%, respectively) and elective
      conditions (47 and 9%) under a single payer. Both groups recognized delays for
      elective surgery. Better access to surgical care under a single payer, seen by
      most Canadians (81%), was not predicted among Americans (44%, p = 0.00012).
      Americans (68%) did not believe a single payer would address workforce shortages,
      while Canadians (68%) disagreed (p = 0.00001). Both groups agree (p = 0.7) that
      personal income is decreased. CONCLUSIONS: US surgeons anticipate benefits and
      problems that Canadian surgeons with direct experience with a single payer do not
      experience. This discrepancy must be recognized during the ongoing debate over
      the future of US health care.

PMID- 21085974
TI  - [Implementation of a palliative care concept in a geriatric acute care hospital].
AB  - To integrate palliative care patients into an acute geriatric ward requires
      extensive and continuous education and preparation of all participating
      professionals. It can be a lengthy process to integrate palliative care concepts
      despite cooperation of the hospital administration. The group of patients to be
      integrated differs from the patients of regular geriatric wards because of a
      higher percentage of relatively young oncologic patients and they differ from a
      regular palliative ward because about 50% are non-oncologic patients, while the
      average age is much higher than in normal palliative care. It is possible to
      integrate specialized palliative care into a regular geriatric ward. Patients
      admitted without palliative intention will benefit the most from ward-integrated
      palliative care if the treatment aim turns this way. Ward-integrated palliative
      care can be an integral part of treating geriatric patients in addition to acute
      geriatric medicine, rehabilitation, and prevention. It can also provide
      caretakers and patients with the benefits from continuity of treatment and care.

PMID- 21085975
TI  - Development and evaluation of vesicular system for curcumin delivery.
AB  - Creams and gels containing curcumin are popularized worldwide and marketed all
      over the world, but even after incorporation of high amount of curcumin in
      topical formulations, significant antioxidant and anti-aging effect could not be
      achieved. Objective of the present study was to develop vesicular system for
      delivery of curcumin to achieve enhanced topical bioavailability. Complex of
      curcumin with phosphatidyl choline (PC) was prepared and characterized on the
      basis of TLC, DSC, melting point and IR spectroscopic analysis. The complex was
      further converted into vesicles (phyto-vesicles). Liposomes and niosomes of
      curcumin were also prepared and all these vesicular formulations were
      incorporated into carbopol gel to make feasible for topical application on skin.
      Anti-aging effects of these formulations were compared with plain curcumin and
      physical mixture of curcumin with phosphatidyl choline in UV-induced oxidative
      stress in mice. Analytical reports along with spectroscopic data revealed the
      formation of the complex. In the present study, the phyto-vesicles were found to
      be most effective than all other formulations and plain curcumin in providing
      enhanced antioxidant and antiaging effect. This increase may be due to the
      amphiphilic nature of the complex, which greatly enhances the water and lipid
      miscibility of the curcumin. This study clearly indicates the superiority of CU
      PC complex and the phyto-vesicles prepared from CU-PC complex over others in
      providing enhanced anti-aging, antioxidant and anti-wrinkle effect.

PMID- 21085976
TI  - Long-term damage to the ENT system in Wegener's granulomatosis.
AB  - The objectives of the study are to describe long-term ENT damage and assess risk
      factors in patients with newly diagnosed and treated Wegener's granulomatosis
      (WG) using the vasculitis damage index (VDI). Data from four randomised
      controlled trials carried out by the European Vasculitis Study Group was used.
      Patients newly diagnosed with WG with complete data at 5 years were included.
      Patients enrolled into the trials without 5-year data were excluded. Total and
      ENT VDI scores were recorded at 12 months and after at least 5 years. Logistic
      regression models were constructed to assess risk factors using total ENT and
      overall VDI score over the follow-up period, the proportion of patients with
      increased VDI score and the presence or absence of damage as the main outcomes.
      One hundred and thirty-eight patients were included. Ninety patients (65%) had
      long-term damage and 81% of these (73/90) developed some damage in the first 12
      months. Positive ENT activity score (BVAS) at baseline and relapses were
      associated with higher ENT VDI scores long-term (OR = 6.90, 95% CI 2.01-23.75; OR
      = 2.65, 95% CI 1.20-5.82). Increasing BVAS score showed a trend towards lower VDI
      scores (OR = 0.93, 95% CI 0.88-0.99). Only ENT relapses and number of relapses
      were associated with an increase in VDI over time (OR = 8.38, 95% CI 3.10-22.68;
      OR = 1.79, 95% CI 1.24-2.58). In conclusion, most of the ENT damage in these
      patients was accrued within 12 months of diagnosis. We have shown an association
      between later ENT damage and the presence of ENT disease at baseline; lower
      initial BVAS and higher rate of disease relapse.

PMID- 21085977
TI  - Complications of hyoid suspension in the treatment of obstructive sleep apnea
      syndrome.
AB  - The objectives of the study are to assess adverse events and complications of
      hyoid suspension (HS) as a treatment of obstructive sleep apnea syndrome (OSAS).
      The study design was cohort. Thirty-nine patients with OSAS and obstruction at
      tongue base level, as assessed by sleep endoscopy, underwent HS. Information
      about adverse events and complications were obtained by reviewing charts and
      patient-completed questionnaires. The mean follow-up period from surgery to last
      control visit was 13.1 months (range 2-38). The charts demonstrated mainly
      adverse events. Minor complications occurred in six patients. No major
      complications were observed. The mean admission duration was 3.3 days (range 2
      5). Twenty-six patients (67%) returned their questionnaires. No association was
      found between completing questionnaires and the success of the intervention (p =
      0.73). The questionnaires were completed on average 25.9 months (range 3.5-51.5)
      after surgery. VAS scores showed a fast decline in complaints regarding taste,
      speech, swallowing and pain. No significant long-term differences were found,
      when comparing the postoperative VAS scores with the preoperative VAS scores. Of
      the 26 evaluable questionnaires, 20 patients (77%) would recommend HS to an
      acquaintance if they suffered from sleep apnea syndrome, when only taking side
      effects into consideration. The intention to give a positive recommendation did
      not seem to be related to the therapeutic success of the intervention. In
      conclusion, this study demonstrates that the complication rate of HS is low and
      that the discomfort is very acceptable.

PMID- 21085978
TI  - Choice of psychological coping in laryngectomized, head and neck squamous cell
      carcinoma patients versus multiple sclerosis patients.
AB  - To be treated for cancer must be a frightening experience. Yet quality of life
      (QoL) of successfully treated cancer patients seems to be relatively similar in
      comparison with QoL of a general population, with psychological coping partly
      responsible for this finding. When measuring choice of coping, the nature of
      coping score levels constituting appropriate scores, and whether score levels
      rely on the context of the disease has not been settled. We have studied the COPE
      coping responses as related to disease in successfully treated head and neck
      squamous cell carcinoma (HNSCC) patient groups (general and laryngectomized), as
      well as compared to multiple sclerosis (MS) patients. The COPE response patterns
      have also been compared to the Beck depression inventory (BDI) scores. Age and
      gender of patients were not directly associated with choice of coping. Within the
      problem-focused coping indexes, the coping index "active coping" was reported to
      be most utilized among HNSCC patients, whereas "coping by suppression" and
      "coping by social support" were most utilized among MS patients. Emotional
      focused coping was most prevalent among HNSCC patients and lowest among the MS
      patients. Level of avoidance coping was similar between the groups. The coping of
      the general HNSCC patients differed most from the MS patients. An association was
      shown between increased coping efforts and lowered mood. In particular, avoidance
      coping was associated with lowered mood. These associations were stronger among
      the MS patients than HNSCC patients. Drinking to cope was most prevalent among
      the laryngectomized group, and was correlated with BDI scores in all groups.
      Furthermore, adequate coping seems to be to limit avoidance coping and promote
      coping by acceptance. The response pattern of the COPE inventory seems to be
      valid among HNSCC and MS patients.

PMID- 21085979
TI  - Analysis of chemokine and chemokine receptor expression in squamous cell
      carcinoma of the head and neck (SCCHN) cell lines.
AB  - The purpose of this work was to analyze chemokine and chemokine receptor
      expression in untreated and in irradiated squamous cell carcinoma of the head and
      neck (SCCHN) tumor cell lines, aiming at the establishment of assays to test for
      the relevance of chemokine and chemokine receptor expression in the response of
      SCCHN to radiotherapy and radiochemotherapy. Five low passage and 10 established
      SCCHN lines, as well as two normal cell lines, were irradiated at 2 Gy or sham
      irradiated, and harvested between 1 and 48 h after treatment. For chemokines with
      CC and CXC structural motifs and their receptors, transcript levels of target and
      reference genes were quantified relatively by real-time PCR. In addition, CXCL1
      and CXCL12 protein expression was analyzed by ELISA. A substantial variation in
      chemokine and chemokine receptor expression between SCCHN was detected.
      Practically, all cell lines expressed CCL5 and CCL20, while CCL2 was expressed in
      normal cells and in some of the tumor cell lines. CXCL1, CXCL2, CXCL3, CXCL10,
      and CXCL11 were expressed in the vast majority of the cell lines, while the
      expression of CXCL9 and CXCL12 was restricted to fibroblasts and few tumor cell
      lines. None of the analyzed cell lines expressed the chemokines CCL3, CCL4, or
      CCL19. Of the receptors, transcript expression of CCR1, CCR2, CCR3, CCR5, CCR7,
      CCXR2, and CCXR3 was not detected, and CCR6, CXCR1, and CXCR4 expression was
      restricted to few tumor cells. Radiation caused up- and down-regulation with
      respect to chemokine expressions, while for chemokine receptor expressions down
      regulations were prevailing. CXCL1 and CXCL12 protein expression corresponded
      well with the mRNA expression. We conclude that the substantial variation in
      chemokine and chemokine receptor expression between SCCHN offer opportunities for
      the establishment of assays to test for the relevance of chemokine and chemokine
      receptor expression in the response of SCCHN to radiotherapy and
      radiochemotherapy.

PMID- 21085980
TI  - A simple and rapid method for constructing ring-X chromosomes in Drosophila
      melanogaster.
AB  - Ring chromosomes are of basic interest to the geneticist and cell biologist who
      study their behavior in meiotic and mitotic divisions. In addition, the mitotic
      instability associated with some ring-X chromosomes has proven useful in
      Drosophila as a means to produce gynandromorphs for developmental studies. We
      describe a method to construct ring-X chromosomes in Drosophila via I-CreI
      mediated exchange in rDNA, and then rapidly diagnose the recovery of ring
      chromosomes via FLP-mediated sister chromatid exchange within the ring. The
      method we describe provides a ready means to tailor the genetic content of ring-X
      chromosomes, making it suited to produce ring-X chromosomes for a variety of
      experimental purposes.

PMID- 21085981
TI  - In response to "current approach to seronegative myasthenia" by Z. Argov.

PMID- 21085982
TI  - Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid
      disease.
AB  - Citotoxin-associated gene-A (CagA)-positive Helicobacter pylori strains have been
      associated with occurrence and destabilization of coronary atherosclerotic
      plaques. However, data on the relationship between CagA-positive H. pylori
      infection and carotid artery instability are lacking. Thus, the role of CagA
      antigen in patients with symptomatic and asymptomatic carotid atherosclerotic
      plaques was investigated. A total of 64 patients with advanced carotid artery
      stenosis, including 33 patients with symptomatic and 31 patients with
      asymptomatic internal carotid artery stenosis, verified by duplex ultrasound, all
      undergoing carotid endarterectomy, were studied. The control group consisted of
      65 subjects without a history or presence of vascular diseases. Serology for H.
      pylori and CagA antigen was assessed in all participants. Specimens of
      atherosclerotic plaques obtained from all patients during carotid endarterectomy
      were analyzed immunohistochemically using anti-CagA monoclonal antibodies. The
      ultrasonographic plaque characteristics were also estimated. CagA antibody titers
      were significantly higher in symptomatic patients (8.8; range, 5.8-32.7) compared
      to asymptomatic patients (4.7; range, 2.1-8.8; P = 0.005) and the control group
      (5.0; range 2.2-7.9; P < 0.001). There was significant difference in echolucency
      (>= 25% soft material) between the symptomatic and asymptomatic groups (P =
      0.034) by ultrasonographic evaluation. Positive immunoreactivity between
      monoclonal CagA antibodies and antigens within atherosclerotic specimens was
      significantly higher among symptomatic patients compared to asymptomatic patients
      (97.0 vs. 74.2%; P = 0.009). H. pylori may play a role in the pathogenesis of the
      atherosclerotic process due to autoimmune mechanisms and even contribute to
      destabilization of carotid atherosclerotic plaques.

PMID- 21085983
TI  - Variability of cardio-respiratory, electromyographic, and perceived exertion
      responses at the walk-run transition in a sample of young men controlled for
      anthropometric and fitness characteristics.
AB  - The cardio-respiratory (heart rate, HR; oxygen uptake, VO(2;) expired carbon
      dioxide, VCO(2); ventilation, VE), electromyographic (EMG; medial gastrocnemius,
      vastus lateralis, rectus femoralis, and anterior tibialis), and perceived
      exertion (PE) responses during a protocol for the determination of the walk-run
      transition speed (WRTS) were investigated. From an initial sample of 453
      volunteers, 12 subjects matched for age, anthropometric characteristics [height,
      weight, lower limb length (LLL)], cardio-respiratory fitness (peak oxygen
      consumption, VO(2peak); ventilatory threshold, VT; maximal HR), and habitual
      physical activity levels were selected (age = 18.6 +/- 0.5 years; height = 174.5
      +/- 1.4 cm; weight = 66.4 +/- 1.1 kg; LLL = 83.3 +/- 1.2 cm, VO(2peak) = 52.2 +/-
      2.2 ml kg(-1) min(-1); VT = 39.8 +/- 2.6 ml kg(-1) min(-1)). The highly
      reproducible WRTS determination protocol (ICC = 0.92; p < 0.0001) consisted in 2
      min warm-up at 5.5 km h(-1) followed by increments of 0.1 km h(-1) every 15 s.
      Between-subjects variability of the measured variables during 24 walking and 12
      running velocities (from 80 to 120% of WRTS) was compared to WRTS variation. The
      coefficient of variation for WRTS was 7.8%, which was within the range of
      variability for age, anthropometric variables, VO(2peak), and maximal HR (from 5
      to 12%). Cardio-respiratory responses at WRTS had a greater variation (VO(2)
      about 50%; VE/VCO(2) about 35%; VE/VO(2) about 45%; HR about 30%). The highest
      variation was found for PE (from 70 to 90%) whereas EMG variables showed the
      lowest variation (from 25 to 30%). Linear regression between EMG series and VO(2)
      data showed that VO(2) reflected the increase in muscle activity only before the
      WRTS. These results support the hypothesis that the walk-run transition
      phenomenon is determined by mechanical variables such as limb length and its
      relationship to biomechanical model rather than by metabolic factors.

PMID- 21085984
TI  - Trial-to-trial sequential dependencies in a social and non-social Simon task.
AB  - Recent research has shown that joint-action effects in a social Simon task
      provide a good index of action co-representation. The present study aimed to
      specify the mechanisms underlying joint action by considering trial-to-trial
      transitions. Using non-social stimuli, we assigned a Simon task to two
      participants. Each was responsible for only one of two possible responses. This
      task was performed alone (Individual go/nogo task) and in cooperation with
      another person who was sitting alongside (Joint go/nogo task). As a further
      control task, we added a Standard Simon task. Replicating previous findings
      (Sebanz et al. in Cognition 88:B11-B21, 2003), we found no spatial compatibility
      effect in the Individual go/nogo task but we did find one in the Joint go/nogo
      task. A more detailed analysis showed that a sequential modulation of the Simon
      effect was present in both the Joint and the Individual go/nogo tasks. We found
      reliable Simon effects in trials following Simon compatible trials not only in
      the Joint go/nogo task but also to a somewhat smaller extent in the Individual
      go/nogo task. For both these go/nogo tasks, sequential modulation effects were
      stronger for nogo/go transitions than for go/go transitions. This suggests that
      low-level feature binding and repetition mechanisms contribute to the social
      Simon effect related to the specific requirement not to respond on nogo trials.

PMID- 21085985
TI  - JPEG2000 for automated quantification of immunohistochemically stained cell
      nuclei: a comparative study with standard JPEG format.
AB  - The Joint Photographic Experts Group (JPEG) standard format is one of the most
      widely used in image compression technologies. More recently, JPEG2000 format has
      emerged as a state-of-the-art technology that provides substantial improvements
      in picture quality at higher compression ratios. However, there has been no
      attempt to date to determine which of the two compression formats produces less
      variability in the automated evaluation of immunohistochemically stained digital
      images in agreement with their compression rates and complexity degrees. The
      evaluation of Ki67 and FOXP3 immunohistochemical nuclear markers was performed in
      a total of 329 digital images: 47 were captured in uncompressed Tagged Image File
      Format (TIFF), 141 were converted to three JPEG compressed formats (47 each with
      1:3, 1:23 and 1:46 compression) and 141 were converted to three JPEG2000
      compressed formats (47 each with 1:3, 1:23 and 1:46 compression). The count
      differences between images in TIFF versus JPEG formats were compared with those
      obtained between images in TIFF versus JPEG2000 formats at the three levels of
      compression. It was found that, using JPEG2000 compression, the results of the
      stained nuclei count are close enough to the results obtained with uncompressed
      images, especially in highly complex images at minimum and medium compression.
      Otherwise, in images of low complexity, JPEG and JPEG2000 had similar count
      efficiency to that of the original TIFF images at all compression levels. These
      data suggest that JPEG2000 could give rise to an efficient means of storage,
      reducing file size and storage capacity, without compromise on the
      immunohistochemical analytical quality.

PMID- 21085986
TI  - Alterations in the tumor suppressor gene p16(INK4A) are associated with
      aggressive behavior of penile carcinomas.
AB  - Alterations in the p16/cyclinD1/Rb and ARF/Mdm2/p53 pathways are frequent events
      in the pathogenesis of squamous cell carcinomas. Different mechanisms of p16
      regulation have been described for penile carcinomas so far. Therefore,
      expression of p16 and p53 was immunohistochemically detected with monoclonal
      antibodies in 52 primary invasive penile squamous cell carcinomas. The carcinomas
      were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for
      mutations in the p16(INK4A) and the p53 gene. In addition, we examined the
      promoter status of p16(INK4A) by methylation-specific PCR. The presence of human
      papilloma virus (HPV) 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Data were
      compared to clinical data. Concerning p16, 26 (50%) tumors showed positive
      immunohistochemistry, 32 (62%) tumors showed allelic loss and 22 tumors (42%)
      showed promoter hypermethylation. All tumors with negative p16
      immunohistochemistry showed LOH near the p16(INK4A) locus and/or hypermethylation
      of the p16(INK4A) promoter. HPV 16 DNA was detected in 17 tumors, ten of them
      with positive p16 immunostaining. The remaining seven tumors with negative p16
      staining showed allelic loss and/or promoter hypermethylation. Evidence of lymph
      node metastasis was significantly associated with negative p16
      immunohistochemistry as well as with combined LOH and promoter hypermethylation
      (p = 0.003 and p = 0.018, respectively). Allelic loss around p53 was found in 22
      tumors (42%), and seven mutations of the p53 gene could be demonstrated in our
      tumors. No correlations could be found between any p53 alteration and clinical
      parameters.

PMID- 21085987
TI  - Hepatic miRNA expression reprogrammed by Plasmodium chabaudi malaria.
AB  - Evidence is accumulating that miRNAs are critically implicated in the outcome of
      diseases, but little information is available for infectious diseases. This study
      investigates the hepatic miRNA signature in female C57BL/6 mice infected with
      self-healing Plasmodium chabaudi malaria. Primary infections result in
      approximately 50% peak parasitemia on day 8 p.i., approximately 80% survival, and
      development of protective immunity. The latter is evidenced as 100% survival and
      1.5% peak parasitemia upon homolog re-infections of those mice which are still
      alive on day 56 after primary infection. Such immune mice exhibit increased
      levels of IgG2a and IgG2b isotypes and still contain P. chabaudi-infected
      erythrocytes in their livers as revealed by light microscopy and PCR analysis.
      Primary infections, but not secondary infections, induce an upregulation of
      hepatic mRNAs encoding IL-1beta, TNFalpha, IFNgamma, NF-kappaB, and iNOS, and a
      downregulation of mRNAs for CYP7A1 and SULT2A2, respectively. Using miRXplore
      microarrays containing 634 mouse miRNAs in combination with quantitative RT-PCR,
      the liver is found to respond to primary infections with an upregulation of the
      three miRNA species miR-26b, MCMV-miR-M23-1-5p, and miR-1274a, and a
      downregulation of the 16 miRNA species miR-101b, let-7a, let-7g, miR-193a-3p, miR
      192, miR-142-5p, miR-465d, miR-677, miR-98, miR-694, miR-374(*), miR-450b-5p, miR
      464, miR-377, miR-20a(*), and miR-466d-3p, respectively. Surprisingly, about the
      same pattern of miRNA expression is revealed in immune mice, and this pattern is
      even sustained upon homolog re-infections of immune mice. These data suggest that
      development of protective immunity against malarial blood stages of P. chabaudi
      is associated with a reprogramming of the expression of distinct miRNA species in
      the female mouse liver.

PMID- 21085988
TI  - Echinococcus multilocularis in south-eastern Europe (Romania).
AB  - Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE)
      in humans, has been found in 4.8% of 561 red foxes originating from various
      regions of Romania. Infected foxes were identified in 8 of 15 counties with
      average prevalence rates between 1.7% and 14.6%. In previous studies, E.
      multilocularis was not found in 535 foxes from three counties, but larval stages
      (metacestodes) were present in four species of rodents. Furthermore, AE was
      diagnosed in two patients. Experiences from other European regions indicate that
      several factors (such as increasing fox populations with higher parasite
      prevalences and urban cycles of the parasite) may result in an increased
      infection risk for humans.

PMID- 21085990
TI  - Ultrastructure of spermiogenesis and mature spermatozoon of Breviscolex
      orientalis (Cestoda: Caryophyllidea).
AB  - Spermiogenesis and spermatozoon ultrastructure of the caryophyllidean cestode
      Breviscolex orientalis Kulakovskaya, 1962, first member of the family
      Capingentidae studied, a parasite of cyprinid fish Abbottina rivularis, are
      described using transmission electron microscopy. Spermiogenesis in B. orientalis
      follows the Type II pattern described by Ba and Marchand (Mem Mus Natl Hist Nat
      166:87-95, 1995) for cestodes. It begins with the formation of a zone of
      differentiation containing a large nucleus and a pair of centrioles. The
      centrioles are separated from one another by an intercentriolar body composed of
      three electron-dense layers. Each centriole is associated with typical striated
      roots. At the beginning of the spermiogenesis, an electron-dense material is
      observed in the apical region of the differentiation zone. During the initial
      stage of spermiogenesis, one of the centrioles gives rise to a free flagellum,
      which then rotates and undergoes proximodistal fusion with the cytoplasmic
      protrusion of the differentiation zone. The mature spermatozoon of B. orientalis
      corresponds to the Type III pattern described by Levron et al. (Biol Rev 85:523
      543, 2010). It is characterized by the absence of mitochondrion and crested body.
      Five regions of the mature spermatozoon are differentiated. The main
      ultrastructural characteristics are: one axoneme of 9+ "1" trepaxonematan
      pattern, cortical microtubules and nucleus. The comparison of the spermiogenesis
      of B. orientalis with those of the other caryophyllidean species demonstrates
      some variation within the order relative to the presence and morphology of the
      intercentriolar body, the presence of slight rotation of the flagellar bud and a
      complete proximodistal fusion of the free flagellum with a cytoplasmic
      protrusion.

PMID- 21085989
TI  - Analysis of differentially expressed genes in the precocious line of Eimeria
      maxima and its parent strain using suppression subtractive hybridization and cDNA
      microarrays.
AB  - The precocious line of Eimeria spp., obtained by repeated passages of oocysts
      initially collected from feces of previously infected chickens, has unique
      phenotypes and plays an important role in immunizing chickens against
      coccidiosis. However, the genetic basis of precocious phenotype in Eimeria is
      still poorly understood. To investigate gene expression changes in sporulated
      oocysts between the precocious line of E. maxima and its parent strain,
      subtractive cDNA libraries were constructed by suppression subtractive
      hybridization (SSH). A total of 3,164 cDNA fragments were selected from the SSH
      cDNA libraries to fabricate cDNA microarrays and further identify the
      differentially expressed genes. The credibility of the microarray data was
      verified by real-time PCR. A total of 360 valid expressed sequence tags (ESTs)
      were obtained, which represented 32 unique sequences. Twenty-one genes were
      validated as downregulated and 11 genes as upregulated in the precocious line.
      Homology searching of the public sequence database showed that six genes encoded
      proteins homologous with previously reported proteins, including rhomboid-like
      protein and transhydrogenase of E. tenella, serpin, and cation-transporting
      ATPase of E. acervulina, a heat-shock protein of E. maxima, and a conserved
      hypothetical protein of Toxoplasma gondii. Thus, the remaining 26 ESTs have not
      been previously reported. Further characterization of these differentially
      expressed genes will be useful in understanding the genetic basis for the
      precocious phenotype in Eimeria spp.

PMID- 21085991
TI  - Comparison of the tick repellent efficacy of chemical and biological products
      originating from Europe and the USA.
AB  - The present paper investigates the efficacy of common anti-tick repellents in
      Europe and in the USA. There were tested Ixodes ricinus, Dermacentor reticulatus,
      and Rhipcephalus sanguineus when they are placed onto hands and clothes of male
      and female humans being treated with common tick repellents. It was seen that
      DEET needed high concentrations to repel ticks, while essential oils are mostly
      inefficient. On the other hand saltidin=icaridin, p-menthan-diol and IR 3535
      showed long-lasting effects, which in the case of combinations of saltidin and
      Vitex extracts were even increased.

PMID- 21085992
TI  - Valeriana wallichii root extracts and fractions with activity against Leishmania
      spp.
AB  - Leishmanial diseases, posing a public health problem worldwide, are caused by
      Leishmania parasites with a dimorphic life cycle alternating between the
      promastigote and amastigote forms. Promastigotes transmitted by the vector are
      transformed into amastigotes residing in the host tissue macrophages. Presently,
      new antiparasitic agents are needed against Leishmania donovani and Leishmania
      major, the respective organisms causing visceral and cutaneous leishmaniasis,
      since the available treatments are unsatisfactory due to toxicity, high cost, and
      emerging drug resistance. Over the years, traditional medicinal flora throughout
      the world enriched the modern pharmacopeia. Hence, roots of 'Indian Valerian'
      (Valeriana wallichii DC) were studied for its antileishmanial activity for the
      first time. The methanol and chloroform extracts showed activity against L.
      donovani promastigotes and both promastigotes and amastigotes of L. major. The
      most active fraction, F3, obtained from the chloroform extract, showed IC(50) at
      ~ 3-7 MUg/ml against both the promastigotes and 0.3 MUg/ml against L. major
      amastigotes. On investigation of the mechanism of cytotoxicity in L. donovani
      promastigotes, the 'hall-mark' events of morphological degeneration, DNA
      fragmentation, externalization of phosphatidyl serine, and mitochondrial membrane
      depolarization indicated that F3 could induce apoptotic death in leishmanial
      cells. Therefore, the present study revealed a novel and unconventional property
      of V. wallichii root as a prospective source of effective antileishmanial agents.

PMID- 21085993
TI  - RNAi silencing of calcium-regulated heat-stable protein of 24 kDa in Schistosoma
      japonicum affects parasite growth.
AB  - The calcium-regulated heat-stable protein of 24 kDa (CRHSP-24) is a major
      calcineurin phosphoprotein that functions in multiple signal transduction
      pathways in cell metabolism. Schistosomes are multicellular parasites that infect
      200 million people worldwide, even though treatment has been available for two
      decades. To determine the function of schistosome CRHSP-24 (SjCRHSP-24), we
      successfully knocked down SjCRHSP-24 in Schistosoma japonicum by RNA interference
      (RNAi). By establishing controls for measuring off-target RNAi effects, we found
      that different double-stranded (dsRNA) sequences had different levels of
      effectiveness. While all tested dsRNAs reduced CRHSP-24 transcript levels, the S2
      dsRNA consistently reduced CRHSP-24 expression to >95% of the control. Knockdown
      of the SjCRHSP-24 gene significantly affected the morphology and vitality of S.
      japonicum.

PMID- 21085995
TI  - Stage transition and laryngeal closure in poststroke patients with dysphagia.
AB  - Timely hyolaryngeal excursion and laryngeal closure are essential for safe
      transfer of the bolus during the pharyngeal swallow. The temporal measures stage
      transition duration (STD) and laryngeal closure duration (LCD) represent these
      physiological events. The purpose of this investigation was to determine whether
      small changes in bolus consistency and volume affect these temporal measures in
      poststroke patients who aspirate, poststroke patients who do not aspirate, and
      nonneurologically impaired control subjects. STD and LCD were obtained by frame
      by-frame analysis of the videofluoroscopic examinations of 5 and 10 ml thin and
      nectar thick liquids. Using a three-way analysis of variance, STD was
      significantly different between the control group and the two poststroke groups;
      however there was no difference between the two stroke groups. There was no
      difference among the three groups on LCD. Bolus consistency and bolus volume had
      no effect. Clinical implications of these findings are discussed.

PMID- 21085994
TI  - High resolution mapping of OCA2 intragenic rearrangements and identification of a
      founder effect associated with a deletion in Polish albino patients.
AB  - Oculocutaneous albinism type 2 (OCA2) represents about 30% of OCA worldwide.
      Using quantitative multiplex fluorescent PCR and very high-resolution array-CGH
      focussed on the OCA2 gene and surrounding regions in 15q12, we identified new
      rearrangements. Deletion 1, encompassing exons 3-20, was present in three
      patients (including one in the homozygous state), and Deletion 2 (exons 1-20) was
      found in one patient (heterozygous state). The duplication (exons 3-20) was found
      in one patient in the homozygous state. Using 14 microsatellite markers we
      determined haplotypes associated with these rearrangements. Deletion 1 was
      associated with the same haplotype in three patients who were all of Polish
      origin, which is strongly in favour of a founder effect. Deletion 2 was
      associated with a distinct haplotype. The homozygous duplication was inherited
      from the two unrelated parents of the patients on two different haplotypes.
      Analysis of the sequences around the breakpoints of these rearrangements showed
      that all occurred within complex arrays of repetitive sequences. The combined use
      of very high-resolution array-CGH and of microsatellites (including new
      intragenic ones described here) constitutes a powerful approach for the precise
      characterization of OCA2 rearrangements, which have been found in more than 20%
      of OCA2 patients.

PMID- 21085996
TI  - Nonepithelial, submucosal gastric tumors: is laparoscopic wedge resection the
      optimal treatment?

PMID- 21085997
TI  - Size of mural nodule as an indicator of surgery for branch duct intraductal
      papillary mucinous neoplasm of the pancreas during follow-up.
AB  - BACKGROUND: A mural nodule is a strong predictive factor for malignancy in branch
      duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but the
      nodule size has hardly been considered. The aim of this study was to investigate
      whether a mural nodule of 10 mm was appropriate as an indicator of surgery for
      IPMN during follow-up. METHODS: The follow-up outcomes of 100 patients who had
      branch duct IPMN without mural nodules or who had branch duct IPMN with mural
      nodules of less than 9 mm in a tertiary care setting were investigated
      retrospectively. The patients underwent abdominal ultrasound (US) every 3 months
      and additional imaging examinations or cytologic examination of pancreatic juice
      when necessary. Surgery was recommended to them when a mural nodule developed or
      when a nodule enlarged and reached 10 mm. RESULTS: During an average follow-up
      period of 97 months, branch duct IPMNs developed mural nodules that reached 10 mm
      in 5 patients (0.62% per year). In one patient the IPMN was revealed to be non
      invasive carcinoma by resection, 1 IPMN was shown to be malignant by further
      follow-up, and 3 were not resected because of refusal or the patient's age. In 7
      patients, mural nodules stayed within 9 mm. The remaining 88 patients lacked
      mural nodules in their branch duct IPMNs throughout the follow-up. The occurrence
      of invasive carcinoma around the IPMN was not indicated by imaging examinations
      in any patient. Univariate analysis showed that the size of the cyst at baseline
      significantly predicted the development of a mural nodule that reached 10 mm
      during follow-up (P = 0.05). CONCLUSIONS: A mural nodule of 10 mm is appropriate
      as an indicator of surgery in the follow-up of branch duct IPMN.

PMID- 21085998
TI  - Arbuscular mycorrhizal fungal diversity and species dominance in a temperate soil
      with long-term conventional and low-input cropping systems.
AB  - The aim of this work was to study the effect of long-term contrasting cropping
      systems on the indigenous arbuscular mycorrhizal fungal (AMF) spore populations
      in the soil of a field experiment located in western Finland. Conventional and
      low-input cropping systems were compared, each with two nutrient management
      regimes. The conventional cropping system with a non-leguminous 6-year crop
      rotation (barley-barley-rye-oat-potato-oat) was fertilized at either full
      (rotation A) or half (rotation B) the recommended rate. In the low-input cropping
      system, plant residues were returned to the plots either as such (rotation C) or
      composted (rotation D). In the rotation of this system, 1 year with barley was
      replaced by clover, and oat was cultivated mixed with pea. Thus, the 6-year
      rotation was barley-red clover-rye-oat + pea-potato-oat + pea. Each rotation was
      replicated three times, starting the 6-year rotation in three different years,
      these being designated point 1, point 2, and point 3, respectively. In the low
      input system, biotite and rock phosphate were used to compensate for K and P in
      the harvested yield, while animal manure was applied at the start only. After 13
      years, rotation points 1 and 3 were studied. Barley was the standing crop in all
      plots of rotation point 1, while oat and oat + pea were grown in rotations C and
      D, respectively. AMF spores were studied by direct extraction and by trapping,
      sampled on 15 June and 15 August. In addition, a special assay was designed for
      isolation of fast colonizing, dominating AMF. The cropping system did not
      significantly affect AMF spore densities, although the low-input cropping system
      with composted plant residues had the highest density with 44 spores on average
      and the conventional system with full fertilization 24 spores per 100 cm(3) soil
      in the autumn samples. Species richness was low in the experimental area. Five
      Glomus spp., one Acaulospora, and one Scutellospora were identified at the
      species level. In addition to these, three unidentified Glomus spp. were found.
      Species richness was not affected by cropping system, rotation point, or their
      interactions. The Shannon-Wiener index of AMF spore distributions was
      significantly higher in the fully fertilized than in the half-fertilized
      conventional plots. Glomus claroideum was the most commonly identified single
      species in the experimental area. It occurred in all the cropping systems and
      their various rotation points, representing about 30% of the total number of
      identified spores. In August, G. claroideum accounted for as much as 45-55% of
      the total numbers of spores identified in the conventional system with halved
      fertilization. In contrast, Glomus mosseae occurred more commonly in June (26%)
      than in August (9%). A bioassay using roots as inoculum for isolation and culture
      of dominating AMF was successfully developed and yielded only G. claroideum. This
      indicates a high probability of being able to more generally identify, isolate,
      and culture fast colonizing generalist AMF for use as inoculants in agriculture
      and horticulture.

PMID- 21085999
TI  - Fenpropimorph and fenhexamid impact phosphorus translocation by arbuscular
      mycorrhizal fungi.
AB  - Fenpropimorph and fenhexamid are sterol biosynthesis inhibitor (SBI) molecules
      widely used to control diseases in agriculture. Both molecules, at increasing
      concentrations, have been shown to impact on the non-target arbuscular
      mycorrhizal (AM) fungi. Root colonization, spore production and mycelium
      architecture, including the branched absorbing structures which are thought to be
      involved in phosphorus (P) uptake, were affected. In the present study, we
      investigated the capacity of Glomus sp. MUCL 43204 to take up, transfer and
      translocate labelled P to Medicago truncatula in the presence of these SBI
      molecules. We used a strict in vitro cultivation system associating an
      autotrophic plant of M. truncatula with the AM fungus. In addition, the effects
      of both SBI molecules on the proportion of hyphae with alkaline phosphatases
      (ALP), succinate dehydrogenase (SDH) activity and on the expression of the
      mycorrhiza-specific plant phosphate transporter MtPT4 gene were examined. We
      demonstrated that the two SBI molecules impacted the AM fungus. This was
      particularly evidenced for fenpropimorph. A decrease in P transport and ALP and
      SDH activities associated with the extraradical mycelium and MtPT4 expression
      level was noted. These three factors were closely related to the development of
      the AM fungus, suggesting a direct impact not only on the AM fungal growth but
      also on the physiology and metabolic activities of the AM fungus. These results
      further emphasized the interest on the autotrophic in vitro culture system as an
      alternative to pot experiments to investigate the mechanisms behind the impact of
      disease control molecules on the non-target AM fungal symbionts.

PMID- 21086000
TI  - Differential response of human bone marrow stromal cells to either TGF-beta(1) or
      rhGDF-5.
AB  - Cell therapy along with growth factor injection is currently widely investigated
      to restore the intervertebral disc. However, there is increasing evidence that
      transplanted unconditioned bone marrow-derived stromal cells (BMSCs) cannot
      thrive in the intervertebral disc "niche". Moreover, uncertainty exists with
      respect to the cell phenotype that would be suitable to inject. The
      intervertebral disc cell phenotype only recently has been started to be
      characterised using transcriptomics profiling. Recent findings suggest that
      cytokeratin 19 (KRT-19) could be used as a potential candidate marker for the
      intervertebral disc, or more specifically the nucleus pulposus cell (NPC)
      phenotype. We present in vitro cell culture data using alginate bead culture of
      primary human BMSCs exposed to the standard chondrogenic stimulus, transforming
      growth factor beta-1 (TGF-beta), the growth and differentiation factor 5 and/or
      bovine NPCs to induce a potential "discogenic" pathway. Chondrogenic induction
      via TGF-beta pathway provoked down-regulation of KRT-19 gene expression in four
      out of five donors after 18 days of culture, whereas KRT-19 expression remained
      unchanged in the "discogenic" groups. In addition, the ratio of aggrecan/collagen
      II gene expression showed a remarkable difference (of at least 3 magnitudes)
      between the chondrogenic stimulus (low ratio) and the discogenic stimulus (high
      ratio). Therefore, KRT-19 and aggrecan/collagen II ratio may be potential markers
      to distinguish chondrogenic from "discogenic" differentiation.

PMID- 21086001
TI  - Chromium is not an essential trace element for mammals: effects of a "low
      chromium" diet.
AB  - Chromium was proposed to be an essential trace element over 50 years ago and has
      been accepted as an essential element for over 30 years. However, the studies on
      which chromium's status are based are methodologically flawed. Whether chromium
      is an essential element has been examined for the first time in carefully
      controlled metal-free conditions using a series of purified diets containing
      various chromium contents. Male Zucker lean rats were housed in specially
      designed metal-free cages for 6 months and fed the AIN-93G diet with no added
      chromium in the mineral mix component of the diet, the standard AIN-93G diet, the
      standard AIN-93G diet supplemented with 200 MUg Cr/kg, or the standard AIN-93G
      diet supplemented with 1,000 MUg Cr/kg. The chromium content of the diet had no
      effect on body mass or food intake. Similarly, the chromium content of the diet
      had no effect on glucose levels in glucose tolerance or insulin tolerance tests.
      However, a distinct trend toward lower insulin levels under the curve after a
      glucose challenge was observed with increasing chromium content in the diet; rats
      on the supplemented AIN-93G diets had significantly lower areas (P < 0.05) than
      rats on the low-chromium diet. The studies reveal that a diet with as little
      chromium as reasonably possible had no effect on body composition, glucose
      metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet.
      Together with the results of other recent studies, these results clearly indicate
      that chromium can no longer be considered an essential element.

PMID- 21086002
TI  - Rates of intercalator-driven platination of DNA determined by a restriction
      enzyme cleavage inhibition assay.
AB  - A restriction enzyme cleavage inhibition assay was designed to determine the
      rates of DNA platination by four non-cross-linking platinum-acridine agents
      represented by the formula [Pt(am(2))LCl](NO(3))(2), where am is a diamine
      nonleaving group and L is an acridine derived from the intercalator 1-[2-(acridin
      9-ylamino)ethyl]-1,3-dimethylthiourea (ACRAMTU). The formation of monofunctional
      adducts in the target sequence 5'-CGA was studied in a 40-base-pair probe
      containing the EcoRI restriction site GAATTC. The time dependence of endonuclease
      inhibition was quantitatively analyzed by polyacrylamide gel electrophoresis. The
      formation of monoadducts is approximately 3 times faster with double-stranded DNA
      than with simple nucleic acid fragments. Compound 1 (am(2) is ethane-1,2-diamine,
      L is ACRAMTU) reacts with a first-order rate constant of k (obs) = 1.4 +/- 0.37 *
      10(-4) s(-1) (t (1/2) = 83 +/- 22 min). Replacement of the thiourea group in
      ACRAMTU with an amidine group (compound 2) accelerates the rate by fourfold (k
      (obs) = 5.7 +/- 0.58 * 10(-4) s(-1), t (1/2) = 21 +/- 2 min), and introduction of
      a propane-1,3-diamine nonleaving group results in a 1.5-fold enhancement in
      reactivity (compound 3, k (obs) = 2.1 +/- 0.40 * 10(-4) s(-1), t (1/2) = 55 +/-
      10 min) compared with the prototype. Derivative 4, containing a 4,9-disubstituted
      acridine threading intercalator, was the least reactive compound in the series (k
      (obs) = 1.1 +/- 0.40 * 10(-4) s(-1), t (1/2) = 104 +/- 38 min). The data suggest
      a correlation may exist between the binding rates and the biological activity of
      the compounds. Potential pharmacological advantages of rapid formation of
      cytotoxic monofunctional adducts over the common purine-purine cross-links are
      discussed.

PMID- 21086003
TI  - Comparison of mesenchymal stem cells and autogenous cortical bone graft in the
      treatment of class II furcation defects in dogs.
AB  - The purpose of this study was to compare the effectiveness of mesenchymal stem
      cells (MSCs) with platelet-rich plasma (PRP) as scaffold and autogenous cortical
      bone (ACB) graft with and without PRP in the regenerative treatment of class II
      furcation defects in dogs. The mandibular second, third, and fourth premolars
      (P2, P3, P4) and maxillary P3 and P4 of both sides in three dogs were selected
      for experimentation. Class II furcation defects (5 mm in height and 2 mm in
      depth) were surgically created. Five weeks after the first operation, scaling +
      root planning (group 1), PRP (group 2), ACB (group 3), combination of ACB/PRP
      (group 4), and combination of MSCs/PRP (group 5) treatments were performed during
      open flap debridement. The percentage of cementum and alveolar bone formation was
      evaluated by histomorphometric analysis after a healing period of 8 weeks. There
      was new cementum along with periodontal ligament and coronal growth of alveolar
      bone in all groups. Cementum formation was significantly higher in groups 3, 4,
      and 5 compared to the control group (P < 0.05) with no significant difference
      between groups 2, 3, 4, and 5. Alveolar bone formation was similar in all groups
      (P > 0.05). It can be concluded that periodontal regeneration with complete
      filling of class II furcation defects with cementum, alveolar bone, and
      periodontal ligament is obtained 8 weeks after ACB, ACB/PRP, and MSCs/PRP
      treatments; however, efficacy of none is higher than another.

PMID- 21086004
TI  - Study of professional practices among rheumatologists in Burgundy: initial
      corticotherapy in polymyalgia rheumatica.
AB  - To study the initial dose of corticoids prescribed by rheumatologists in the Cote
      d'Or, a French department of Burgundy, in the treatment of polymyalgia rheumatica
      (PMR), the clinical and biological data of patients who consulted rheumatologists
      of the Cote d'Or between March 2006 and December 2008 for PMR were collected. The
      statistical analyses concerned the initially prescribed dose of prednisone: the
      median, mean, and standard deviation were calculated cumulatively and then for
      individual rheumatologists; the Mann-Whitney test was used to compare the mean
      initial doses prescribed with regard to (a) the main practice of the practitioner
      (private-practice or hospital rheumatologist), (b) the presence of clinical signs
      of severity, (c) severity of the inflammatory syndrome, and (d) the presence of
      clinical relapse with the decrease in corticoids. Ninety-nine patients were
      included (age = 72 +/- 8.6 years, 59% women). The mean dose of prednisone
      prescribed was 27.4 +/- 12.4 mg/day. Considerable inter- and intra-individual
      variabilities in the doses prescribed were noted. There was no significant
      difference concerning the dose prescribed according to the clinical severity or
      the type of practice. However, the dose was significantly higher (34.3 +/- 14.7
      vs. 25.5 +/- 11.1 mg/day) in patients with a high sedimentation rate. Clinical
      relapse was not statistically linked to the initial dose of corticoids. This
      evaluation of professional practices among French rheumatologists shows that the
      initial dose of prednisone prescribed in PMR varies considerably and is higher
      than the dose currently recommended in the literature (15 mg/day).

PMID- 21086005
TI  - Delays in recognition and management of giant cell arteritis: results from a
      retrospective audit.
AB  - Prompt institution of corticosteroids (CS) can prevent devastating neuro
      ophthalmic complications (NOC) in patients with giant cell arteritis (GCA).
      Guidelines on managing GCA place emphasis on early recognition of symptoms and
      prompt treatment of the disease where there is a high index of clinical
      suspicion. The aims of this study are to review the clinical findings in patients
      with GCA, evaluate the baseline practice in diagnosis and treatment and to
      identify delays in treating patients with NOC. The study utilised retrospective
      case notes review of patients diagnosed with GCA between 2003 and 2008. Sixty
      five patients were identified (47 females, 18 males, mean age, 75 years). A
      significant minority presented with constitutional, polymyalgic and ischaemic
      symptoms. Mean time from symptom onset to diagnosis of GCA was 35 days. CS were
      not delayed in those diagnosed with GCA. Recognition of ischaemic symptoms was
      slow. Visual loss at presentation occurred in 16 patients (24.6%). Ten patients
      (15.4%) presented with NOC in the absence of headache, seven (70%) of whom
      developed permanent visual impairment. Five (7.7%) patients had cerebrovascular
      complications. There are major delays in the recognition and treatment of GCA.
      There is a high incidence of irreversible ischaemic complications which may
      partly result from diagnostic and treatment delay.

PMID- 21086006
TI  - Appropriateness of blood culture testing parameters in routine practice. Results
      from a cross-sectional study.
AB  - We aimed to assess the appropriateness of routine blood culture testing
      parameters and antimicrobial therapy for patients with suspected bloodstream
      infection. We conducted a cross-sectional study of blood cultures registered in
      the microbiological laboratory at a university-affiliated hospital from 4 to 15
      June 2007. Using a structured implicit chart review, two infectious disease
      specialists assessed the appropriateness of the testing parameters and
      antimicrobial therapy. Overall, 2,696 blood culture bottles were collected from
      260 patients during their stay, including 955 bottles that were evaluated during
      the study period. The indication of fungal and bacterial blood cultures was rated
      as appropriate for 75% (95% confidence interval [CI], 65-83) and 91% (95% CI, 87
      95) of patients. Only 45% (95% CI, 39-52) of patients had an adequate number of
      blood cultures (i.e., two to four). An optimal volume of blood (i.e., >=10 mL)
      was inoculated in 13% (95% CI, 11-15) of adult bottles. Empirical antimicrobial
      therapy was appropriate for 60% (95% CI, 43-76) of patients with positive blood
      cultures. There is room for improvement regarding routine blood culture testing
      parameters and antimicrobial therapy. The effectiveness of multifaceted
      interventions in altering the appropriateness of blood culture parameters
      deserves further research.

PMID- 21086007
TI  - Precipitating factors in the pathogenesis of peritonsillar abscess and
      bacteriological significance of the Streptococcus milleri group.
AB  - Peritonsillar abscess (PTA) is conventionally considered to be a complication of
      acute tonsillitis, but no pathogenical association has been demonstrated. To
      investigate the precipitating factors in the pathogenesis of PTA, the clinical
      status of 117 patients with PTA and 78 patients with peritonsillar cellulitis
      (PC) were reviewed, comparing them with 188 cases of acute tonsillitis as a
      control group. The period between the onset of symptoms and the date of starting
      hospitalized medication was 4 to 5 days in all the three groups, with no
      significant differences. Higher prevalence of smoking habit was noted in the PTA
      group (odds ratio, 1.92; 95% confidence interval, 1.17-3.16). Bacteriological
      culture revealed that 55 of 67 aerobic isolates were Streptococcus subspecies,
      with the Streptococcus milleri group (SMG) as the most common (20 isolates).
      Twenty-three anaerobic species were isolated. Only 51% of the patients with
      neither the SMG nor anaerobic bacteria were smokers, whereas 90% of the patients
      with both the SMG and anaerobic bacteria were smokers. We hypothesize that delay
      or failure to receive medical care do not contribute to the pathogenesis of PTA
      or PC, and that smoking is positively correlated with the occurrence of PTA, as
      well as the bacteriological character.

PMID- 21086008
TI  - Development of a multiplexed bead-based immunoassay for the simultaneous
      detection of antibodies to 17 pneumococcal proteins.
AB  - Presently, several pneumococcal proteins are being evaluated as potential vaccine
      candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA,
      PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003,
      SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based
      immunoassay (xMAP((r)) Technology, Luminex Corporation) to simultaneously
      quantify antibodies against these 17 pneumococcal proteins in serum. The median
      fluorescence intensity (MFI) values obtained for human pooled serum with the
      multiplex assay were between 82% and 111% (median 94%) of those obtained with the
      singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged
      from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged
      from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal
      antibody levels exhibited extensive inter-individual variability in young
      children suffering from invasive pneumococcal disease. All proteins, including
      the proteins with, as yet, unknown function, were immunogenic. In conclusion, the
      multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible.
      This assay can be used to monitor anti-S. pneumoniae antibody responses in a
      material- and time-saving manner.

PMID- 21086009
TI  - The effect of a single episode of antimicrobial photodynamic therapy in the
      treatment of experimental periodontitis. Microbiological profile and cytokine
      pattern in the dog mandible.
AB  - The purpose of this study was to evaluate the effect of a single application of
      antimicrobial photodynamic therapy (aPDT) on microbiological profile and cytokine
      pattern in dogs. Periodontal disease was induced by placing 3.0 silk ligatures
      around the mandibular pre-molars bilaterally during 8 weeks. The dogs were
      randomly treated with aPDT using a dye/laser system, scaling and root planning
      (SRP), or with the association of treatments (SRP + aPDT). Plaque samples were
      collected at baseline, 1, 3, and 4 weeks, and the mean counts of 40 species were
      determined using DNA-DNA hybridization. Gingival biopsies were removed and the
      expression of tumor necrosis factor alpha (TNF-alpha), receptor activator of NF
      kB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP-1),
      interleukin (IL) 6, IL-10 and total bacterial load by analysis of 16 S rRNA gene
      were evaluated through real-time PCR. The results shows that the levels of the
      majority of the species were reduced 1 week post-therapy for all treatments,
      however, an increase in counts of Prevotella intermedia (p = 0.00), Prevotella.
      nigrescens (p = 0.00) and Tannerella forsythia (p = 0.00) was observed for aPDT
      and SRP + aPDT. After 4 weeks, a regrowth of Porphyromonas gingivalis (p = 0.00)
      and Treponema denticola (p = 0.00), was observed for all treatments. Also, a
      strikingly reduction of counts on counts of Aggregatibacter actinomycetemcomitans
      was observed for the aPDT (p = 0.00). For the cytokine pattern, the results were
      similar for all treatments, and a reduction in the expression of cytokines and
      bacterial load was observed throughout the study. Our results suggest that SRP,
      aPDT in a single application, and SRP + aPDT affects different bacterial species
      and have similar effects on the expression of cytokines evaluated during the
      treatment of ligature-induced periodontitis.

PMID- 21086010
TI  - Effects of low level laser therapy (808 nm) on physical strength training in
      humans.
AB  - Recent studies have investigated whether low level laser therapy (LLLT) can
      optimize human muscle performance in physical exercise. This study tested the
      effect of LLLT on muscle performance in physical strength training in humans
      compared with strength training only. The study involved 36 men (20.8+/-2.2 years
      old), clinically healthy, with a beginner and/or moderate physical activity
      training pattern. The subjects were randomly distributed into three groups: TLG
      (training with LLLT), TG (training only) and CG (control). The training for TG
      and TLG subjects involved the leg-press exercise with a load equal to 80% of one
      repetition maximum (1RM) in the leg-press test over 12 consecutive weeks. The
      LLLT was applied to the quadriceps muscle of both lower limbs of the TLG subjects
      immediately after the end of each training session. Using an infrared laser
      device (808 nm) with six diodes of 60 mW each a total energy of 50.4 J of LLLT
      was administered over 140 s. Muscle strength was assessed using the 1RM leg-press
      test and the isokinetic dynamometer test. The muscle volume of the thigh of the
      dominant limb was assessed by thigh perimetry. The TLG subjects showed an
      increase of 55% in the 1RM leg-press test, which was significantly higher than
      the increases in the TG subjects (26%, P = 0.033) and in the CG subjects (0.27%,
      P < 0.001). The TLG was the only group to show an increase in muscle performance
      in the isokinetic dynamometry test compared with baseline. The increases in thigh
      perimeter in the TLG subjects and TG subjects were not significantly different
      (4.52% and 2.75%, respectively; P = 0.775). Strength training associated with
      LLLT can increase muscle performance compared with strength training only.

PMID- 21086011
TI  - Questionnaire survey of the current status of radical trachelectomy in Japan.
AB  - BACKGROUND: The number of young patients with cervical cancer has been increasing
      recently in Japan. Radical trachelectomy is a potential option for patients who
      wish to preserve their fertility, but its status is not clear. The present survey
      was conducted to clarify the status of radical trachelectomy in Japan. METHODS:
      Questionnaires were mailed to 164 selected institutions based on tumor
      registration with the Japanese Obstetrics Gynecology Society. The subjects were
      patients undergoing radical trachelectomy between 2000 and 2008. RESULTS: The
      response rate to the questionnaire was 88.4% (145/164). Radical trachelectomy was
      performed on 269 patients in 26 institutions (17.9%) . Most cases (74.7%,
      201/269) underwent an abdominal approach. Three institutions had performed more
      than 21 cases (max. 61 cases), whereas 8 institutions had performed only one
      case. Twenty pregnancies and 13 deliveries were achieved and the frequency of
      delivery later than the 29th gestational week was 62% (8/13). "Tumor size <=2 cm
      (81%)" and "stage <=Ib1 (96%)" were commonly regarded as indications for radical
      trachelectomy. On the other hand, 46% of the centers did not consider the
      histological type as an indication. CONCLUSION: This survey is the first report
      on the current status of radical trachelectomy in Japan. It reveals a difference
      in the criteria for surgery applied in each institution.

PMID- 21086012
TI  - Rectal intussusception is associated with abnormal levator ani muscle structure
      and morphometry.
AB  - BACKGROUND: Anorectal symptoms are common in urogynaecological patients, and so
      are anatomical abnormalities of the anorectum associated with such symptoms. One
      such abnormality is rectal intussusception (RI). The aim of this retrospective
      study was to determine the prevalence of RI in a tertiary urogynaecological
      population and to describe the associated symptoms, signs and ultrasound
      findings, in particular those relating to pelvic floor function and anatomy. It
      was hypothesized that RI is associated with abnormal levator ani muscle anatomy
      and function. METHODS: The electronic records and volume imaging datasets of 967
      women who presented to a tertiary urogynaecological clinic between May 2005 and
      March 2009 were analysed. Rectal intussusception was diagnosed on translabial
      ultrasound and findings were analysed against symptoms and hiatal area in the
      levator ani muscle. RESULTS: Rectal intussusception was found in 38 women (3.9%)
      and was more prevalent with increasing age (p = 0.014) and vaginal parity (p =
      0.037). It was associated with symptoms of prolapse (p = 0.005), incomplete bowel
      emptying (p < 0.001), vaginal digitation (p < 0.001), and faecal incontinence (p
      = 0.022). RI was more common in patients with a clinical diagnosis of enterocele
      (p = 0.03) and rectocele (p = 0.002). On imaging, RI was associated with an
      increased hiatal area on valsalva (p < 0.001) and levator ani avulsion (p =
      0.003). CONCLUSION: Rectal intussusception is not an uncommon finding in
      urogynaecological patients. While often asymptomatic, it is associated with
      symptoms of vaginal prolapse, incomplete bowel emptying, vaginal digitation and
      faecal incontinence, and with abnormal levator ani structure and morphometry.

PMID- 21086014
TI  - Infralevator leiomyoma.

PMID- 21086013
TI  - A brief review of laparoscopic appendectomy: the issues and the evidence.
AB  - Laparoscopic appendectomy was first performed more than 25 years ago. We
      performed a systematic literature search on laparoscopic appendectomy and
      selected related topics. The technique should be considered the gold standard for
      surgical removal of the appendix in women of childbearing age (level of evidence
      Ia). There is minor but consistent evidence that it should also be advocated for
      men (level of evidence III), obese (level of evidence III), and elderly (level of
      evidence IIb) patients, while there is some evidence of unfavorable results on
      pregnant women (level of evidence IIb). Studies reporting higher incidence of
      intra-abdominal abscesses after laparoscopic appendectomy are difficult to
      interpret due to a lack of standardization of the operative technique and lack of
      uniformity related to the different grades of disease (ranging from uninflamed
      appendix to diffuse peritonitis, gangrene, or perforation of the organ). As far
      as surgical technique, the three-port procedure is superior to needleoscopy and
      single port access (level of evidence Ia). Costly high-tech instruments for
      dissection are mostly unnecessary (level Ib). Mechanical closure of the stump
      might prove safer (level Ib). The quantity of peritoneal lavage fluid is
      generally scanty (level III), and abdominal drains are not useful (level Ia).
      Fast-track protocols should be implemented (level Ic). Training and technical
      standardization are the key to devising future trials on this topic.

PMID- 21086015
TI  - Quantitative evaluation of evaporation rate during spin-coating of polymer blend
      films: Control of film structure through defined-atmosphere solvent-casting.
AB  - Thin films of polymer mixtures made by spin-coating can phase separate in two
      ways: by forming lateral domains, or by separating into distinct layers. The
      latter situation (self-stratification or vertical phase separation) could be
      advantageous in a number of practical applications, such as polymer
      optoelectronics. We demonstrate that, by controlling the evaporation rate during
      the spin-coating process, we can obtain either self-stratification or lateral
      phase separation in the same system, and we relate this to a previously
      hypothesised mechanism for phase separation during spin-coating in thin films,
      according to which a transient wetting layer breaks up due to a Marangoni-type
      instability driven by a concentration gradient of solvent within the drying film.
      Our results show that rapid evaporation leads to a laterally phase-separated
      structure, while reducing the evaporation rate suppresses the interfacial
      instability and leads to a self-stratified final film.

PMID- 21086016
TI  - Structural and thermodynamic properties of a linearly perturbed matrix model for
      RNA folding.
AB  - The structural and thermodynamic properties of a matrix model of homo-RNA folding
      with linear external interaction are studied. The interaction distinguishes
      paired bases of the homo-RNA chain from the unpaired bases hence dividing the
      possible RNA structures given by the linear model into two structural regimes.
      The genus distribution functions show that the total number of structures for any
      given length of the chain are reduced for the simple linear interaction
      considered. The partition function of the model exhibits a scaling relation with
      the matrix model in which the base pairing strength parameter is re-scaled (G.
      Vernizzi, H. Orland, A. Zee, Phys. Rev. Lett. 94, 168103 (2005)). The
      thermodynamics of the model are computed for i) largely secondary structures,
      (with tertiary structures suppressed by a factor 10(-4)) and ii) secondary plus
      tertiary structures. A structural change for large even lengths is observed in
      the free energy and specific heat. This change with largely secondary structures
      appears much before (with respect to length of the chain) than when all the
      structures (secondary and pseudoknots) are considered. The appearance of
      different structures which dominate the ensemble with varying temperatures is
      also found as a function of the interaction parameter for different types of
      structures (given by different numbers of pairings).

PMID- 21086017
TI  - Pharmacoeconomic evaluation of tiotropium bromide in the long-term treatment of
      chronic obstructive pulmonary disease (COPD) in Italy.
AB  - The randomized, double-blind trial UPLIFT((r)) demonstrated in 5,993 patients
      with moderate to very severe COPD that 4 years of tiotropium bromide therapy were
      associated with improvements in lung function, exacerbations, quality of life,
      and mortality compared with placebo. The pharmacoeconomic evaluation was
      performed through a probabilistic, patient-level simulation Markov model. Routine
      COPD care (RC) was compared with the inclusion of tiotropium bromide on it. The
      analysis was conducted over a lifetime horizon, with 1 year cycles and a 3.5%
      annual discount rate. Patients were characterized by gender, age, height, smoking
      status, and forced expiratory volume in 1 s (FEV1). FEV1 time trend was modeled
      according to the annual decline recorded in UPLIFT(r). Mortality derived from
      that of the general Italian population was adjusted by smoking status and FEV1.
      Health utilities derived from published Italian observational studies and were
      varied in time according to UPLIFT(r) data. Exacerbation rates were derived from
      a published Italian observational prospective study. The cost perspective was
      that of the Italian National Health Service. Healthcare resource consumption for
      RC and exacerbations derived from Italian observational studies were valued
      according to current price and tariffs. Simulated patients in the tiotropium arm
      gained an average (95% CI) 0.50 (-1.63 to 6.27) Life Years (LYs) and 0.42 (-0.25
      to 3.05) Quality-Adjusted Life Years (QALYs). The incremental lifetime cost
      resulted ?3,357 (-?10,669 to ?29,820). The incremental cost-effectiveness ratio
      (ICER) was ?6,698/LY and ?7,916/QALY. In the cost-effectiveness acceptability
      curve (CEAC), tiotropium had a 90% probability of being cost-effective for a
      willingness to pay (WTP) threshold of ? 10,000/QALY.

PMID- 21086018
TI  - Rigid registration of medical images using 1D and 2D binary projections.
AB  - Image registration is a necessary procedure in everyday clinical practice.
      Several techniques for rigid and non-rigid registration have been developed and
      tested and the state-of-the-art is evolving from the research setting to
      incorporate image registration techniques into clinically useful tools. In this
      paper, we develop a novel rigid medical image registration technique which
      incorporates binary projections. This technique is tested and compared to the
      standard mutual information (MI) methods. Results show that the method is
      significantly more accurate and robust compared to MI methods. The accuracy is
      well below 0.5 degrees  and 0.5 mm. This method introduces two more improvements
      over MI methods: (1)for 2D registration with the use of 1D binary projections, we
      use minimal interpolation; and (2) for 3D registration with the use of 2D binary
      projections the method converges to stable final positions, independent of the
      initial misregistration.

PMID- 21086019
TI  - The negative prognostic value of TRAIL overexpression in oral squamous cell
      carcinomas does not preclude the potential therapeutic use of recombinant TRAIL.

PMID- 21086020
TI  - Optimal conditions for multifocal VEP recording for normal Japanese population
      established by receiver operating characteristic analysis.
AB  - The purpose of this study was to establish optimal conditions for recording
      multifocal visual evoked potentials (mVEPs) in Japanese individuals, whose skull
      frame presumably differs from Caucasians. The scalp point that was extended from
      the calcarine fissure was identified using magnetic resonance imaging scans of
      200 subjects. MVEPs were recorded from 56 individuals using three single channels
      and combinations of vertical and horizontal channels. Five electrodes were placed
      at the inion, 4 cm above the inion, 2.5 cm below the inion, 4 cm to the left or 4
      cm to the right of the inion. The signal-to-noise ratio (SNR) was obtained by
      measuring the root-mean-square (RMS) amplitude of a signal window (45-150 ms)
      from each of 60-local responses that was divided by the average of the 60 RMS
      amplitudes of the noise window (325-430 ms). Receiver operating characteristic
      (ROC) analyses were performed based on the proportion of mVEP responses that
      exceeded a specific SNR criterion, calculated for both the signal window and the
      noise window. The position of the calcarine fissure relative to the inion was
      significantly lower than the value reported for Caucasians. The ROC analyses
      disclosed that bi-channel combinations (one vertical and one horizontal) had
      significantly better performance to discriminate signal from noise in 60-local
      mVEP responses compared to any single channel and performed similarly to the tri
      channel combination. Two sets of perpendicular channels should be simultaneously
      used in recording mVEP responses from Japanese people, among whom skull frame
      characteristics differ from those observed in Caucasians.

PMID- 21086022
TI  - The decline in stomach cancer mortality: exploration of future trends in seven
      European countries.
AB  - Mortality from stomach cancer has fallen steadily during the past decades. The
      aim of this paper is to assess the implication of a possible continuation of the
      decline in stomach cancer mortality until the year 2030. Annual rates of decline
      in stomach cancer mortality from 1980 to 2005 were determined for the
      Netherlands, United Kingdom, France, and four Nordic countries on the basis of
      regression analysis. Mortality rates were extrapolated until 2030, assuming the
      same rate of decline as in the past, using three possible scenarios. The absolute
      numbers of deaths were projected taking into account data on the ageing of
      national populations. Stomach cancer mortality rates declined between 1980 and
      2005 at about the same rate (3.6-4.9% per year) for both men and women in all
      countries. The rate of decline did not level off in recent years, and it was not
      smaller in countries with lower overall mortality rates in 1980. If this decline
      were to continue into the future, stomach cancer mortality rates would decline
      with about 66% between 2005 and 2030 in most populations, while the absolute
      number of stomach cancer deaths would diminish by about 50%. Thus, in view of the
      strong, stable and consistent mortality declines in recent decades, and despite
      population ageing, stomach cancer is likely to become far less important as a
      cause of death in Europe in the future.

PMID- 21086021
TI  - Heparin-associated anti-Xa activity and platelet-derived prothrombotic and
      proinflammatory biomarkers in moderate to high-risk patients with acute coronary
      syndrome.
AB  - Heparin compounds, to include fractionated and unfractionated preparations, exert
      both antithrombotic and antiinflammatory effects through combined inhibition of
      factor Xa and thrombin. The contribution of modulated platelet activity in vivo
      is less clearly defined. The SYNERGY library was a prospectively designed
      repository for candidate clinical, hemostatic, platelet, and molecular biomarkers
      from patients participating in SYNERGY--a large-scale, randomized clinical trial
      evaluating the comparative benefits of unfractionated heparin (UFH) and
      enoxaparin in high-risk patients with acute coronary syndrome (ACS). Samples were
      collected from 201 patients enrolled at 26 experienced, participating sites and
      shipped to established core laboratories for analysis of platelet, endothelium
      derived, inflammatory and coagulation activity biomarkers. Tissue factor pathway
      inhibitor (TFPI)--a vascular endothelial cell-derived factor Xa regulatory
      protein-correlated directly with plasma anti-Xa activity (unadjusted: r = 0.23, P
      < 0.0001; adjusted: beta = 0.10; P = 0.001), as did TFPI-fXa complexes
      (unadjusted: r = 0.34, P < 0.0001; adjusted: beta = 0.38; P = < 0.0001). In
      contrast, there was a direct and inverse relationship between anti-Xa activity
      and two platelet-derived biomarkers-plasminogen activator inhibitor-1
      (unadjusted: r = -0.18, P = 0.0012; adjusted: beta = -0.10; P = 0.021) and
      soluble CD40 ligand (unadjusted: r = -0.11, P = 0.05; adjusted: beta = -0.13; P =
      0.049). All measured analyte relationships persisted after adjustment for age,
      creatinine clearance, weight, sex, and duration of treatment. Differences in
      biomarkers between patients receiving UFH and those randomized to enoxaparin were
      not observed. The ability of heparin compounds to affect the prothrombotic and
      proinflammatory states which characterize ACS may involve factor Xa-related
      modulation of platelet activation and expression. Whether this potentially
      beneficial effect is direct or indirect and achieved, at least in part, through
      the release of endothelial cell-derived coagulation regulatory proteins will
      require further investigation.

PMID- 21086023
TI  - Effects of low level microwave radiation on carcinogenesis in Swiss Albino mice.
AB  - This study concerns with the multiple treatment of the target site to potent
      carcinogen and the super imposition of low level radiofrequency and microwave
      radiation. Swiss albino mice (male) were used for this investigation. The study
      has been divided in two parts, part A: a single dose of 7,12
      dimethylbenz(a)anthracene (DMBA) 100 MUg/animal was applied topically on the skin
      of mice and were exposed to 112 MHz amplitude modulated (AM) at 16 Hz (power
      density 1.0 mW/cm(2), specific absorption rate (SAR) 0.75 W/kg). Similarly after
      a single dose of DMBA, mice were exposed to 2.45 GHz radiation (power density of
      0.34 mW/cm(2), SAR, 0.1 W/kg), 2 h/day, 3 days a week for a period of 16 weeks.
      The two sets of experiments were carried out separately. Part B: mice were
      transplanted intraperitoneally (ip) with ascites 8 * 10(8) (Ehrlich-Lettre
      ascites, strain E) carcinoma cells per mouse. These mice were exposed to 112 MHz
      amplitude modulated at 16 Hz and 2.45 GHz radiation separately for a period of 14
      days. There was no tumor development in mice exposed to RF and MW. Similarly a
      topical application of single dose of DMBA followed by RF/MW exposure also did
      not produce any visible extra tumor on the skin of mice. On the other hand mice
      were transplanted intraperitoneally with ascites (8 * 10(8) cell/ml) and
      subsequently exposed to above mentioned fields for 14 days showed a slight
      increase in the cell numbers as compared to the control group. However, the
      increase is insignificant. There were insignificant differences either in the
      mortality or cell proliferation among the control and exposed group. This results
      show that low level RF or MW do not alter tumor growth and development as
      evidenced by no observable change in tumor size.

PMID- 21086024
TI  - Phytotoxic volatiles in the roots and shoots of Artemisia tridentata as detected
      by headspace solid-phase microextraction and gas chromatographic-mass
      spectrometry analysis.
AB  - In the vicinity of big sagebrush (Artemisia tridentata), the growth of Nicotiana
      attenuata is negatively affected, in part due to the alleopathic effect of methyl
      jasmonate (MeJA) which is produced in large quantities by the aerial parts of
      sagebrush. Preliminary experiments suggested that growth-inhibiting substances
      were being emitted from the sagebrush roots. To identify the allelochemical
      secondary metabolites, we tested different root extracts in seedling growth
      bioassays with the naturally co-occurring native tobacco, Nicotiana attenuata, in
      a two-chamber Petri dish assay, optimized for tests of volatiles. Fractions rich
      in volatile compounds were particularly phytotoxic. We analyzed the volatiles
      emitted from the roots of intact Artemisia tridentata plants grown in soil, sand,
      and hydroponic cultures by using dynamic headspace extraction, headspace solvent
      microextraction (HSME) and headspace solid-phase microextraction (HSPME), and GC
      MS. Camphor, 1,8-cineol, nerol, and neryl isovalerate were phytotoxic and
      released as the major constituents. In addition to the phytotoxic monoterpenes,
      himachalenes, longifolene, caryophyllene, and acetylenic spiroethers, were found
      as characteristic components in the root's volatiles. The allelopathic potential
      of these root volatiles was compared with that of methyl jasmonate (MeJA), one of
      the most active compounds emitted from above-ground parts of the plant.

PMID- 21086025
TI  - Inhibition of xanthine oxidase activity results in the inhibition of Russian
      wheat aphid-induced defense enzymes.
AB  - The role of xanthine oxidase (XO) in the defense response of wheat (Triticum
      aestivum L.) against the Russian wheat aphid (RWA) (Diuraphis noxia) was studied.
      Xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine to uric
      acid, and oxygen radicals that are formed as a by-product at both of these
      oxidation steps may participate in plant defense reactions. A resistant wheat
      cultivar (Tugela DN), and a close isogenic susceptible cultivar (Tugela), were
      infested with 20-30 aphids per plant before inhibiting xanthine oxidase by adding
      allopurinol as a soil drench to the resistant plants. Increases in H(2)O(2)
      content were detected early after infestation in the resistant wheat, and the
      downstream defense related responses, chitinase and peroxidase activities, were
      selectively induced by RWA infestation. These downstream defense responses were
      substantially inhibited in allopurinol treated-resistant wheat, presumably as a
      response to inhibition of XO, and superoxide dismutase (SOD). We conclude that
      the production of active oxygen species through the XO system plays an important
      role in the induction of defense reactions in wheat against the RWA.

PMID- 21086026
TI  - Anxiety and asthma symptoms in urban adolescents with asthma: the mediating role
      of illness perceptions.
AB  - Twenty to 40% of adolescents with asthma experience significant symptoms of
      anxiety. This study examined the mediational role of illness perceptions in the
      relationship between anxiety and asthma symptoms in adolescents. One hundred
      fifty-one urban adolescents (ages 11-18) with asthma completed measures of
      illness perceptions, and anxiety and asthma symptoms. Using the Baron and Kenny
      approach and Sobel tests, we examined whether illness perceptions mediated the
      anxiety-asthma symptom relationship. Three illness perceptions significantly
      mediated the relationship between anxiety and asthma symptoms, z = 1.97-2.13, p <
      .05; adjusted R(2) = 0.42-0.51, p < .05. Greater anxiety symptoms were associated
      with perceptions that asthma negatively impacted one's life and emotions and was
      difficult to control. These negative illness perceptions were, in turn, related
      to greater asthma symptoms. Illness perceptions helped explain the anxiety-asthma
      symptoms link in adolescents. Results suggest that targeting illness perceptions
      in adolescents with asthma and anxiety may help reduce asthma symptoms.

PMID- 21086027
TI  - Parental overprotection, perceived child vulnerability, and parenting stress: a
      cross-illness comparison.
AB  - The current study sought to investigate differences in parenting capacity
      variables across four disease groups. Parents (N = 425), the majority of whom
      were mothers, of children with either cancer, asthma, Type 1 diabetes, or cystic
      fibrosis, completed measures of parental overprotection, perceived child
      vulnerability, and parenting stress. After controlling for significant
      demographic variables, parents of children with cystic fibrosis and asthma
      reported higher perceived child vulnerability than parents of children with
      either diabetes or cancer, while parents of children with asthma and diabetes
      reported higher parenting stress than parents of children with cancer or cystic
      fibrosis. No differences between disease groups were found for parental
      overprotection. The current study provides support for an illness-specific
      approach to understanding parenting capacity variables in the context of
      childhood chronic illnesses.

PMID- 21086028
TI  - The digital divide at an urban community health center: implications for quality
      improvement and health care access.
AB  - Health care policy encourages better electronic connectivity between patient and
      the office practice. However, whether patients are able to partner with the
      practice in using communication technologies is not known. We sought to determine
      (1) the proportion of clinic patients who use internet and cell phone text
      messaging technologies, (2) the level of patient interest in using these
      technologies for the purpose of managing clinical appointments and patient
      education. Consecutive adult patients, clinicians and staff at an urban community
      health center were surveyed during a one-week period in order to estimate the
      frequency of technology use by patients. A total of 308 survey cards were
      collected during the designated week (response rate of 85% (308/362). One-third
      (34.0%, 105) of surveyed patients used the internet and text messaging daily or
      weekly, while nearly two-thirds (59.7%, 182) never used these technologies. There
      were no racial or gender differences in the proportion of patients who used the
      internet daily or weekly. In contrast, African-Americans used text messaging more
      often than whites (28.2 vs. 21.4%, P < .05), and females more than males (30.8
      vs. 18.5%, P < .05). Younger patients (>50) used the internet and text messaging
      more often than older patients (50.6 vs. 16.6%, 44.3 vs. 7.3%, respectively).
      Despite the low use of both technologies, patient's interest in managing clinic
      appointments was high (40.3% for the Internet and 56.8% for text messaging).
      Clinicians and staff estimated patient's daily/weekly use of internet and
      cellphone messaging at 40.3% (+/- 22.0), and 56.8% (+/- 25.7), respectively. Most
      patients at this urban community health center reported never using the internet
      or cell phone text messaging. Clinicians overestimated technology use by
      patients. Planning for clinic infrastructure, quality improvement, and patient
      education should include assessment of technology use patterns by patients.

PMID- 21086029
TI  - Planck-Benzinger thermal work function: thermodynamic characterization of the
      carboxy-terminus of p53 peptide fragments.
AB  - The thermodynamic parameters for six p53 carboxy-terminus peptide fragments as
      determined by analytical ultracentrifugal analysis were compared over the
      experimental temperature range of 275-310 K to evaluate the Gibbs free energy
      change as a function of temperature, DeltaG degrees (T), from 0 to 400 K using
      our general linear third-order fitting function, DeltaG degrees (T) = alpha +
      betaT2 + gammaT3. Data obtained at the typical experimental temperature range are
      not sufficient to accurately describe the variations observed in the
      oligomerization of these p53 fragments. It is necessary to determine a number of
      thermodynamic parameters, all of which can be precisely assessed using this
      general third-order linear fitting function. These are the heat of reaction,
      innate temperature-invariant enthalpy, compensatory temperatures and the
      thermodynamic molecular switch occurring at the thermal set point. This
      methodology can be used to distinguish the characteristic structure and stability
      of p53 carboxy-terminal fragments or other p53 mutants. It should be used for the
      thermodynamic characterization of any interacting biological system.

PMID- 21086030
TI  - Mitochondrial matters of the brain: mitochondrial dysfunction and oxidative
      status in epilepsy.
AB  - Epilepsy is a neurological disorder characterized by spontaneous, recurrent and
      paroxysmal cerebral discharge, clinically leading to persistent alterations in
      function and morphology of neurons. Oxidative stress is one of possible
      mechanisms in the pathogenesis of epilepsy. Oxidative stress resulting from
      mitochondrial dysfunction gradually disrupts the intracellular calcium
      homeostasis, which modulates neuronal excitability and synaptic transmission
      making neurons more vulnerable to additional stress, and leads to neuronal loss
      in epilepsy. In addition, the high oxidative status is associated with the
      severity and recurrence of epileptic seizure. Hence, treatment with antioxidants
      is critically important in epileptic patients through scavenging the excessive
      free radicals to protect the neuronal loss. In this review, we reviewed the
      recent findings that focus on the role for antioxidants in prevention of
      mitochondrial dysfunction and the correlation between oxidative status and
      disease prognosis in patients with epilepsy.

PMID- 21086031
TI  - Metabolis brain disease.

PMID- 21086032
TI  - Extracellular brain ammonia levels in association with arterial ammonia,
      intracranial pressure and the use of albumin dialysis devices in pigs with acute
      liver failure.
AB  - In acute liver failure (ALF) hyperammonemia plays a mayor role in the
      pathogenesis of hepatic encephalopathy (HE) but does not always correlate with
      the severity of mental deterioration and intracranial pressure (ICP). The aim of
      our study was to evaluate the association with extracellular brain ammonia, ICP
      and the therapeutical impact of two albumin dialysis devices. ALF was induced by
      complete hepatectomy in 13 pigs. All pigs were monitored and treated under
      intensive care conditions until death. Arterial blood and cerebral microdialysis
      samples were collected and ICP data recorded. Additionally in 5 pigs, standard
      albumin dialysis and in 3 animals an albumin dialysis prototype was initiated as
      a tool. Arterial ammonia increased straight after hepatectomy, while
      extracellular brain ammonia remained on a moderate level 10 h post ALF
      initiation. After 16 h the brain ammonia reached arterial ammonia levels before
      plateauing at 1,200 microM, though the arterial ammonia continued to rise. The
      ICP correlated with the brain ammonia levels. No impact of the different dialysis
      therapies on neither blood nor brain ammonia levels was observed. In ALF the
      extracellular brain ammonia revealed a delayed increase compared to arterial
      ammonia. It correlated strongly with the ICP and could serve as a sensitive
      marker for HE development. Albumin dialysis did not affect blood or brain ammonia
      levels.

PMID- 21086033
TI  - The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): a scale to assist
      the diagnosis of Autism Spectrum Disorder in adults: an international validation
      study.
AB  - The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) is a valid and
      reliable instrument to assist the diagnosis of adults with Autism Spectrum
      Disorders (ASD). The 80-question scale was administered to 779 subjects (201 ASD
      and 578 comparisons). All ASD subjects met inclusion criteria: DSM-IV-TR,
      ADI/ADOS diagnoses and standardized IQ testing. Mean scores for each of the
      questions and total mean ASD vs. the comparison groups' scores were significantly
      different (p < .0001). Concurrent validity with Constantino Social Responsiveness
      Scale-Adult = 95.59%. Sensitivity = 97%, specificity = 100%, test-retest
      reliability r = .987. Cronbach alpha coefficients for the subscales and 4 derived
      factors were good. We conclude that the RAADS-R is a useful adjunct diagnostic
      tool for adults with ASD.

PMID- 21086034
TI  - Public policy action and CCC implementation: benefits and hurdles.
AB  - Policy change continues to be an increasingly effective means of advancing the
      agenda of comprehensive cancer control. Efforts have moved progressively from
      describing how public policy can enhance the comprehensive cancer control agenda
      to implementation of public policy best practices at both the state and federal
      levels. The current political and economic contexts bring additional challenges
      and opportunities to the efforts surrounding comprehensive cancer control and
      policy. The purpose of this paper is to highlight recent policy successes, to
      illustrate the importance of policy as a means of advancing the comprehensive
      cancer control agenda, and to discuss continued policy action as we move forward
      in a time of healthcare reform and continuing economic uncertainty.

PMID- 21086035
TI  - Comprehensive cancer control programs and coalitions: partnering to launch
      successful colorectal cancer screening initiatives.
AB  - Colorectal cancer control has long been a focus area for Comprehensive Cancer
      Control programs and their coalitions, given the high burden of disease and the
      availability of effective screening interventions. Colorectal cancer control has
      been a growing priority at the national, state, territorial, tribal, and local
      level. This paper summarizes several national initiatives and features several
      Comprehensive Cancer Control Program colorectal cancer control successes.

PMID- 21086036
TI  - Association of progesterone receptor polymorphism with idiopathic recurrent
      pregnancy loss in Taiwanese Han population.
AB  - PURPOSE: Recurrent pregnancy loss (RPL) could be caused by insufficient
      progesterone in the luteal phase of menstruation and early pregnancy.
      Progesterone plays a critical role in oocyte maturation, embryo implantation and
      placenta maintenance in early gestation. This study was set out to investigate
      the association between polymorphisms of the progesterone receptor (PGR) gene and
      idiopathic RPL. METHODS: One hundred twenty-one women with a history of
      idiopathic recurrent pregnancy loss (RPL) and 179 control subjects were enrolled
      into the study. Six tag SNPs and two functional SNPs [PROGINS (rs1042838), +331
      C/T (rs10895068)] of the progesterone receptor gene were genotyped. RESULTS: We
      found that the allele and genotype frequencies of the functional SNP [PROGINS
      (rs1042838)] were both significantly higher in patients with idiopathic RPL than
      in the control subjects (both P values = 0.006). In addition, the C-C haplotype,
      which consists of rs590688C > G and rs11224592T > C, is associated with a
      decreased risk of RPL (p = 0.004). CONCLUSION: PROGINS polymorphism confers
      susceptibility to idiopathic recurrent pregnancy loss in Taiwanese Han women.

PMID- 21086037
TI  - Deconstructing the promise of embryonic stem-cell research.

PMID- 21086038
TI  - Subnuclear targeting of the RNA-binding motif protein RBM6 to splicing speckles
      and nascent transcripts.
AB  - RNA-binding motif (RBM) proteins comprise a large family of RNA-binding proteins
      whose functions are poorly understood. Since some RBM proteins are candidate
      alternative splicing factors we examined whether one such member of the family,
      RBM6, exhibited a pattern of nuclear distribution and targeting consistent with
      this role. Using antibodies raised against mouse RBM6 to immunostain mammalian
      cell lines we found that the endogenous protein was both distributed diffusely in
      the nucleus and concentrated in a small number of nuclear foci that corresponded
      to splicing speckles/interchromatin granule clusters (IGCs). Tagged RBM6 was also
      targeted to IGCs, although it accumulated in large bodies confined to the IGC
      periphery. The basis of this distribution pattern was suggested by the targeting
      of tagged RBM6 in the giant nuclei (or germinal vesicles (GVs)) of Xenopus
      oocytes. In spread preparations of GV contents RBM6 was localized both to
      lampbrush chromosomes and to the surface of many oocyte IGCs, where it was
      confined to up to 50 discrete patches. Each patch of RBM6 labelling corresponded
      to a bead-like structure of 0.5-1 microm diameter that assembled de novo on the
      IGC surface. Assembly of these novel structures depended on the repetitive N
      terminal region of RBM6, which acts as a multimerization domain. Without this
      domain, RBM6 was no longer excluded from the IGC interior but accumulated
      homogeneously within it. Assembly of IGC-surface structures in mammalian cell
      lines also depended on the oligomerization domain of RBM6. Oligomerization of
      RBM6 also had morphological effects on its other major target in GVs, namely the
      arrays of nascent transcripts visible in lampbrush chromosome transcription
      units. The presence of oligomerized RBM6 on many lampbrush loops caused them to
      appear as dense structures with a spiral morphology that appeared quite unlike
      normal, extended loops. This distribution pattern suggests a new role for RBM6 in
      the co-transcriptional packaging or processing of most nascent transcripts.

PMID- 21086040
TI  - No association of polymorphisms in the cell polarity gene SCRIB with breast
      cancer risk in German population.

PMID- 21086039
TI  - Many functions of the meiotic cohesin.
AB  - Sister chromatids are held together from the time of their formation in S phase
      until they segregate in anaphase by the cohesin complex. In meiosis of most
      organisms, the mitotic Mcd1/Scc1/Rad21 subunit of the cohesin complex is largely
      replaced by its paralog named Rec8. This article reviews the specialized
      functions of Rec8 that are crucial for diverse aspects of chromosome dynamics in
      meiosis, and presents some speculations relating to meiotic chromosome
      organization.

PMID- 21086041
TI  - Are fish the victims of 'speciesism'? A discussion about fear, pain and animal
      consciousness.
AB  - Fish welfare is currently a hotly debated topic; this is mainly due to the issue
      of whether or not fish have the capacity for conscious awareness, or subjective
      states. Because of the contentious nature of animal consciousness, the subject is
      often avoided in many welfare arguments, but it is argued that since welfare
      should be about how animals feel, this issue is unavoidable. There is also good
      reason to believe that the issue of assessing subjective states is not as
      insurmountable as some believe.

PMID- 21086042
TI  - An unusual case of anti-glomerular basement membrane disease presenting with
      nephrotic syndrome.
AB  - Anti-glomerular basement membrane (anti-GBM) disease is a vasculitic disease
      characterized by acute kidney injury, oliguria, hematuria and proteinuria.
      Proteinuria is rarely in the nephrotic range. A case of anti-GBM disease with
      proteinuria of 22.5 g/day is discussed. Immunofluorescence showed strong linear
      IgG deposits while electron microscopy showed widespread visceral epithelial cell
      foot cell process effacement. No electron dense immune complex-type deposits were
      identified. Pathology findings were not suggestive of simultaneous presentation
      of anti-GBM disease and other diseases associated with nephrotic range
      proteinuria. Anti-GBM disease should be considered in a comprehensive
      differential diagnosis of severe proteinuria.

PMID- 21086043
TI  - Safety and regulation of yeasts used for biocontrol or biopreservation in the
      food or feed chain.
AB  - Yeasts have been important components of spontaneous fermentations in food and
      beverage processing for millennia. More recently, the potential of utilising
      antagonistic yeasts, e.g. Pichia anomala and Candida spp., for post-harvest
      biological control of spoilage fungi during storage of plant-derived produce
      ('biopreservation') has been clearly demonstrated. Although some yeast species
      are among the safest microorganisms known, several have been reported in
      opportunistic infections in humans, including P. anomala and bakers' yeast,
      Saccharomyces cerevisiae. More research is needed about the dominant
      pathogenicity and virulence factors in opportunistic yeasts, and whether
      increased utilisation of biopreservative yeasts in general could contribute to an
      increased prevalence of yeast infections. The regulatory situation for yeasts
      used in post-harvest biocontrol is complex and the few products that have reached
      the market are mainly registered as biological pesticides. The qualified
      presumption of safety (QPS) approach to safety assessments of microorganisms
      intentionally added to food or feed, recently launched by the European Food
      Safety Authority, can lead to more efficient evaluations of new products
      containing microbial species with a sufficient body of knowledge or long-term
      experience on their safety. P. anomala is one of several yeast species that have
      been given QPS status, although the status is restricted to use of this yeast for
      enzyme and metabolite production purposes. With regard to authorisation of new
      biopreservative yeasts, we recommend that the possibility to regulate
      microorganisms for food biopreservation as food additives be considered.

PMID- 21086044
TI  - Singlet and triplet excited state properties of natural chlorophylls and
      bacteriochlorophylls.
AB  - Ten naturally occurring chlorophylls (a, b, c (2), d) and bacteriochlorophylls
      (a, b, c, d, e, g) were purified and studied using the optical spectroscopic
      techniques of both steady state and time-resolved absorption and fluorescence.
      The studies were carried out at room temperature in nucleophilic solvents in
      which the central Mg is hexacoordinated. The comprehensive studies of singlet
      excited state lifetimes show a clear dependency on the structural features of the
      macrocycle and terminal substituents. The wide-ranging studies of triplet state
      lifetime demonstrate the existence of an energy gap law for these molecules. The
      knowledge of the dynamics and the energies of the triplet state that were
      obtained in other studies allowed us to construct an energy gap law expression
      that can be used to estimate the triplet state energies of any (B)chlorophyll
      molecule from its triplet lifetime obtained in a liquid environment.

PMID- 21086045
TI  - Unintentional struck by/struck against injury mortality in the United States,
      1999-2006.
AB  - Our study described demographics and trend analysis in unintentional struck
      by/struck against fatalities in the United States from 1999 to 2006, and
      identifies the changes in deaths for specific population subgroups. Mortality
      data came from the CDC's Web-based Injury Statistics Query and Reporting System.
      Trends during 1999-2006 were analyzed by gender, age group and race. Annual
      percentage change in deaths/rates and log-linear regression was used for time
      trend analysis from 1999 to 2006, and examines its significance. During 1999
      2006, there were 7,049 deaths; 6,236 (88.5%; 0.56 per 100,000) males, 6,180
      (87.7%; 0.32 per 100,000) whites, and 1,925 (27.3%) aged 45-59 years. Overall
      deaths declined by 4.4% during 1999 to 2006 (P = 0.047 for time-related trend).
      The proportion of deaths was almost similar among males and females (1.1% vs.
      0.3%; P = 0.58), and whites and blacks (0.8% vs. 0.7%; P = 0.44). Almost 21% of
      all deaths occur in only three states of the US i.e., Texas (n = 592; 0.35 per
      100,000), California (n = 513; 0.18) and Florida (n = 375; 0.28). Sub-group
      analysis showed, injury mortality decreased 5% in males and 1% in females, this
      change was not statistically significant overtime in both sexes. Prevention
      efforts for struck by/struck against fatalities should be strengthened and
      surveillance for these deaths should continue to follow future trends.

PMID- 21086046
TI  - 1/f neural noise reduction and spike feature extraction using a subset of
      informative samples.
AB  - This article describes a study on neural noise and neural signal feature
      extraction, targeting real-time spike sorting with miniaturized microchip
      implementation. Neuronal signature, noise shaping, and adaptive bandpass
      filtering are reported as the techniques to enhance the signal-to-noise ratio
      (SNR). A subset of informative samples of the waveforms is extracted as features
      for classification. Quantitative and comparative experiments with both
      synthesized and animal data are included to evaluate different feature extraction
      approaches. In addition, a preliminary hardware implementation has been realized
      using an integrated circuit.

PMID- 21086047
TI  - Advances and challenges in phenylketonuria.

PMID- 21086048
TI  - Effects of untreated and thermally treated lupin protein on plasma and liver
      lipids of rats fed a hypercholesterolemic high fat or high carbohydrate diet.
AB  - Lupin protein is capable of reducing plasma lipids in hypercholesterolemic man
      and animals. Whether lipid-lowering properties of lupin protein will be
      influenced by thermal treatment or by other nutrients has not been elucidated. In
      a two-factorial study, rats were fed hypercholesterolemic diets based on high
      amounts of carbohydrates (HC) or fat (HF), which contained either (20.4% of
      energy) untreated or thermally treated lupin protein (steam: 120  degrees C, 30
      min) or casein as control protein. Lupin protein lowered plasma lipid
      concentrations in rats fed the HF diet but not in those fed the HC diet (P<0.05).
      Among rats fed the HF diet, plasma and VLDL triglyceride concentrations were
      lower in rats fed thermally treated (-46% and -44%, P<0.05) and untreated lupin
      protein (-47% and -46%, P<0.05) than in those fed casein; whereas liver
      triglycerides were reduced only in rats fed untreated lupin protein (P<0.05).
      Compared to casein, untreated lupin protein had slightly stronger cholesterol
      lowering effects in plasma, LDL and HDL (-34%, -37%, -35%; P<0.05) than thermally
      treated lupin protein (-23%, -29%, -31%, P<0.10). In conclusion, the lipid
      lowering effect of lupin protein strongly depends on composition of the basal
      diet, and thermal treatment is accompanied by a slight reduction of its
      hypocholesterolemic properties.

PMID- 21086049
TI  - Category cued recall following controlled encoding as a neuropsychological tool
      in the diagnosis of Alzheimer's disease: a review of the evidence.
AB  - Aim of the present review paper was to evaluate the hypothesis (included in the
      proposal of new research criteria for Alzheimer's disease; Dubois et al., Lancet
      Neurology, 6, 734-746, 2007) that a neuropsychological tool which provides
      support for the semantic encoding of memorandum at the time of study and supplies
      category cues at the time of retrieval (i.e. the Grober-Buschke paradigm) is more
      effective than traditional measures of free recall in 1) differentiating patients
      affected by the amnestic form of Mild Cognitive Impairment (MCI) or by mild to
      moderate forms of Alzheimer's disease (AD) from healthy matches, 2) predicting
      the conversion of individuals with MCI to AD, and 3) differentiating AD patients
      from individuals affected by other forms of dementia. Results of the review are
      controversial regarding the superiority of the Grober-Buschke procedure in
      differentiating individuals affected by AD or MCI from healthy individuals. The
      only study that evaluated this issue directly found that the Grober-Buschke
      procedure was more sensitive and specific than more traditional memory tests in
      predicting the conversion of MCI patients to AD. Finally, two studies reported
      that patients affected by AD or other forms of dementia showed different
      performance patterns in the free and cued recall tasks of the Grober-Buschke
      procedure. In conclusion, although encouraging results are reported in the few
      studies that investigated the ability of this procedure to predict the evolution
      of individuals with amnestic MCI and to differentiate AD patients from patients
      with other forms of cortical and subcortical dementia, more experimental work is
      needed to confirm these positive findings.

PMID- 21086050
TI  - An optimal decision making model for supporting week hospital management.
AB  - Week Hospital is an innovative inpatient health care organization and management,
      by which hospital stay services are planned in advance and delivered on week-time
      basis to elective patients. In this context, a strategic decision is the optimal
      clinical management of patients, and, in particular, devising efficient and
      effective admission and scheduling procedures, by tackling different requirements
      such as beds' availability, diagnostic resources, and treatment capabilities. The
      main aim is to maximize the patient flow, by ensuring the delivery of all
      clinical services during the week. In this paper, the optimal management of Week
      Hospital patients is considered. We have developed and validated an innovative
      integer programming model, based on clinical resources allocation and beds
      utilization. In particular, the model aims at scheduling Week Hospital patients'
      admission/discharge, possibly reducing the length of stay on the basis of an
      available timetable of clinical services. The performance of the model has been
      evaluated, in terms of efficiency and robustness, by considering real data coming
      from a Week Hospital Rheumatology Division. The experimental results have been
      satisfactory and demonstrate the effectiveness of the proposed approach.

PMID- 21086051
TI  - Controlling for quality in the hospital cost function.
AB  - This paper explores the relationship between the cost and quality of hospital
      care from the perspective of applied microeconomics. It addresses both
      theoretical and practical complexities entailed in incorporating hospital quality
      into the estimation of hospital cost functions. That literature is extended with
      an empirical analysis that examines the use of 15 Patient Safety Indicators
      (PSIs) as measures of hospital quality. A total operating cost function is
      estimated on 2,848 observations from five states drawn from the period 2001 to
      2007. In general, findings indicate that the PSIs are successful in capturing
      variation in hospital cost due to adverse patient safety events. Measures that
      rely on the aggregate number of adverse events summed over PSIs are found to be
      superior to risk-adjusted rates for individual PSIs. The marginal cost of an
      adverse event is estimated to be $22,413. The results contribute to a growing
      business case for inpatient safety in hospital services.

PMID- 21086052
TI  - Travelling bioethics.

PMID- 21086053
TI  - In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma:
      characterization of somatostatin receptor expression and role of subtype 5.
AB  - Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of
      hyperthyroidism and account for less than 2% of pituitary adenomas. Medical
      therapy with somatostatin analogues (SSAs) effectively reduces TSH secretion in
      approximately 80% of patients and induces shrinkage in about 45% of tumors.
      According with previous data, resistance to SSA treatment might be due to
      heterogeneity in somatostatin receptors (SSTRs) expression. We report the case of
      TSHoma in a 41-year-old man treated with octreotide LAR that caused a dramatic
      decrease of TSH and thyroid hormones and tumor shrinkage already after 3 months
      of pre-surgical therapy. In search of potential molecular determinants of
      octreotide effectiveness, we measured, in primary cultures from this tumor, SSTR
      and dopamine D2 receptor (D2R) expression, and octreotide and/or cabergoline
      effects on TSH secretion and cell proliferation. SSTR5 and D2R expression was
      higher than SSTR2. Octreotide significantly inhibited TSH secretion more
      effectively than cabergoline (P<0.001), whereas the combined treatment was
      comparable with cabergoline alone. Similarly, octreotide resulted more effective
      than cabergoline on cell proliferation, while the combination did not show any
      additive or synergistic effects. In conclusion, the significant antisecretive and
      antiproliferative effect of octreotide in this patient might be related to the
      high expression of SSTR5, in the presence of SSTR2. After reviewing the
      literature, indeed, in line with previous observations, we hypothesize that
      SSTR5/SSTR2 ratio in TSHomas may represent a useful marker in predicting the
      outcome of therapy with SSAs. The role of D2R should be further explored
      considering that the presence of D2R can influence SSTRs functionality.

PMID- 21086054
TI  - Same-day thyroidectomy: a review of practice patterns and outcomes for 1,168
      procedures in New York State.
AB  - BACKGROUND: There has been a shift of procedures from the inpatient to the
      outpatient setting. Same-day thyroidectomy (SDT) has been reported in high-volume
      single-institution series, but few studies have evaluated its widespread use.
      METHODS: Patients undergoing thyroidectomy for benign and malignant thyroid
      disease were abstracted from the 2004 New York State inpatient (SID) and
      ambulatory surgery (SASD) databases. SDTs were discharged on the same day as
      their surgery. Patient and provider (surgeon and hospital volume) characteristics
      were associated with outcomes, including probability of SDT versus hospital
      admission and 30-day rehospitalization, by bivariate and multivariate analyses.
      RESULTS: A total of 6,762 thyroidectomies were identified; 17% (1,168) were SDTs.
      Patients undergoing SDT compared to thyroidectomy with admission were more often
      white (80 vs. 65%, P < 0.001), with private insurance (80 vs. 70%, P < 0.001) and
      fewer comorbidities (96 vs. 89% with Charlson scores of none/low, P < 0.001). SDT
      was performed more often by high-volume surgeons (48 vs. 31%, P < 0.001) and at
      high-volume hospitals (61 vs. 35%, P < 0.001). Rehospitalization rates of 1.4 and
      2.4% were observed for SDT and inpatient thyroidectomy, respectively (P = NS). In
      multivariate analysis, thyroidectomy by a high-volume surgeon was associated with
      a higher chance of same-day discharge (odds ratio = 2.3, P < 0.001). CONCLUSION:
      Nearly 20% of thyroidectomy patients undergo SDT in New York State. They have
      different demographic and clinical characteristics than patients undergoing
      thyroidectomy who are admitted. There seem to be a few high-volume surgeons and
      centers with extensive SDT experience. More research is needed to explore
      optimized patient triage and patterns of referral to centers of excellence.

PMID- 21086055
TI  - Identification of differentially expressed microRNA in parathyroid tumors.
AB  - BACKGROUND: The molecular factors that control parathyroid tumorigenesis are
      poorly understood. In the absence of local invasion or metastasis, distinguishing
      benign from malignant parathyroid neoplasm is difficult on histologic
      examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and
      benign and malignant parathyroid tumors to better understand the molecular
      factors that may play a role in parathyroid tumorigenesis and that may serve as
      diagnostic markers for parathyroid carcinoma. METHODS: miRNA arrays containing
      825 human microRNAs with four duplicate probes per miRNA were used to profile
      parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples
      normalized to four reference normal parathyroid glands. Differentially expressed
      miRNA were validated by real-time quantitative TaqMan polymerase chain reaction
      (PCR). RESULTS: One hundred fifty-six miRNAs in parathyroid hyperplasia, 277
      microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas
      were significantly dysregulated as compared with normal parathyroid glands [false
      discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid
      carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were
      significantly dysregulated between parathyroid carcinoma and parathyroid adenoma.
      Receiver-operating characteristic curve analysis showed mir-126* was the best
      diagnostic marker, with area under the curve of 0.776. CONCLUSIONS: Most miRNAs
      are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most
      miRNAs are upregulated. miRNA profiling shows distinct differentially expressed
      miRNAs by tumor type which may serve as helpful adjunct to distinguish
      parathyroid adenoma from carcinoma.

PMID- 21086056
TI  - Investigation of the efficacy of a bevacizumab-cetuximab-cisplatin regimen in
      treating head and neck squamous cell carcinoma in mice.
AB  - The efficacy of bevacizumab plus cetuximab-based chemotherapy remains unclear in
      head and neck squamous cell carcinoma (HNSCC). The aim of this study was to
      investigate the anticancer efficacy of a bevacizumab-cetuximab-cisplatin triple
      agent combination in treating mouse HNSCC. SCC-VII tumor-bearing C3H mice were
      treated with bevacizumab, cetuximab and cisplatin either alone or in various
      combinations. In vivo results showed that the largest delay in tumor growth and
      the maximum increase in survival were not in the triple-agent combination
      therapy, but in the bevacizumab plus cisplatin therapy. TUNEL assay showed that
      the apoptosis indices in bevacizumab plus cisplatin group and a triple-agent
      combination group were 31.6 +/- 12.0% and 6.9 +/- 1.3%, respectively. Western
      blot showed that down-regulation of Bcl-2 and up-regulation of cleaved caspase-3
      contributed to the anticancer effect of a triple-agent combination and
      bevacizumab plus cisplatin. Moreover, the maximum level of cleaved caspase-3
      expression was not found in the triple-agent combination group but in the
      bevacizumab plus cisplatin group. Bevacizumab plus cisplatin therapy is better
      than bevacizumab-cetuximab-cisplatin triple therapy in the mouse HNSCC model. Our
      findings suggest that the bevacizumab-cetuximab-cisplatin regimen may not be
      suitable for treating HNSCC.

PMID- 21086057
TI  - Substance use, depression, and mental health functioning in patients seeking
      acute medical care in an inner-city ED.
AB  - The study investigated the behavioral health of a consecutive sample of 5,641
      adult emergency department (ED) patients aged 19 through 60 presenting for
      medical care in a large, inner-city hospital ED. Twenty-three percent met the
      criteria for major depression; average mental health functioning, as measured by
      the mental health component of the SF-12, was half of a standard deviation lower
      than in the general population; 15% met the criteria for alcohol or drug
      abuse/dependence in the past year. Comorbidity was high. These behavioral health
      disorders may complicate treatment and diagnosis of the chief presenting
      complaint. These findings, coupled with the high rates of these disorders,
      suggest the importance of screening and either beginning appropriate treatment or
      offering appropriate referral for such disorders in ED settings.

PMID- 21086058
TI  - Anastomotic leakage contributes to the risk for systemic recurrence in stage II
      colorectal cancer.
AB  - PURPOSE: In stage II colorectal cancer (CRC), high-risk patient selection is
      required, but no candidate markers have been elucidated. Our concern was whether
      anastomotic leakage (Lk) is a potential available clinicopathological factor for
      selecting high-risk stage II. METHODS: Two hundred seven patients with stage II
      CRC who underwent curative resection were analyzed. Clinical variables were
      tested for their relationship to survival. RESULTS: The 5-year disease-free
      survival rate (DFS) was 87.0%. The univariable prognostic analyses indicated that
      Lk (P = 0.003) was the only significant factor. The multivariable prognostic
      analysis revealed that Lk remained to be potently independent [hazard ratio (HR),
      4.21, P = 0.021), and the DFS was 58.3% in cases with Lk, while 88.7% in the
      counterpart. The multivariable logistic regression analysis revealed
      perioperative blood transfusion (P = 0.001) was independently associated with Lk.
      Intriguingly, Lk was closely associated with hematogenic recurrence (P = 0.003)
      rather than peritoneal or local recurrence. Although sustained increase of the
      serum C-reactive protein at 2 weeks after operation predicted poor prognosis, the
      mutitivariable analysis including the C-reactive protein level revealed that Lk
      still indicated the prognostic potential (HR, 3.70, P = 0.075). CONCLUSIONS: The
      findings concluded that Lk may be a high risk for systemic recurrence in stage II
      CRC.

PMID- 21086059
TI  - Assessing stress in surgery: using validated tools to improve patient safety.

PMID- 21086060
TI  - Boas' sign revisited.

PMID- 21086061
TI  - The relationship between anthropometric measures, blood gases, and lung function
      in morbidly obese white subjects.
AB  - BACKGROUND: Obesity may cause adverse effects on the respiratory system. The main
      purpose of this study was to investigate how various measures of obesity are
      related to arterial blood gases and pulmonary function. METHODS: This is a cross
      sectional study of consecutive morbidly obese patients with normal lung function.
      Blood gas samples were taken from the radial artery after 5 min of rest with
      subjects sitting upright. Lung function measurements included dynamic spirometry,
      static lung volumes, and gas diffusing capacity. RESULTS: The 149 patients (77%
      women) had a mean (SD) age of 43 years (11 years) and BMI of 45.0 kg/m(2) (6.3
      kg/m(2)). The mean expiratory reserve volume (ERV) was less than half (49%) of
      predicted value, whilst most other lung function values were within predicted
      range. Forty-two patients had an abnormally low pO2 value (<10.7 kPa [80 mmHg]),
      while eight patients had a high pCO2 value (>6.0 kPa [45 mmHg]). All
      anthropometric measures correlated significantly with decreasing pO2 and
      increasing pCO2 (all P values < 0.05). BMI, neck circumference (NC), and waist
      circumference (WC) were negatively correlated with ERV (r = -0.25, -0.19, -0.21,
      respectively, all P values < 0.05). Multiple linear regression showed that BMI,
      WC, and NC were significantly associated with pO2 after adjustments for age,
      gender, and pack-years (all P values < 0.001). The models explained 34-36% of the
      variations in pO2. BMI, NC, and WC were also significantly associated with pCO2
      (all P values < 0.05).There was no significant association between waist-to-hip
      ratio and blood gases (both P values > 0.27). CONCLUSIONS: Both central and
      overall obesity were associated with unfavorable blood gases and low ERV.

PMID- 21086062
TI  - Duodenal-jejunal bypass surgery does not increase skeletal muscle insulin signal
      transduction or glucose disposal in Goto-Kakizaki type 2 diabetic rats.
AB  - BACKGROUND: Duodenal-jejunal bypass (DJB) has been shown to reverse type 2
      diabetes (T2DM) in Goto-Kakizaki (GK) rats, a rodent model of non-obese T2DM.
      Skeletal muscle insulin resistance is a hallmark decrement in T2DM. The aim of
      the current work was to investigate the effects of DJB on skeletal muscle insulin
      signal transduction and glucose disposal. It was hypothesized that DJB would
      increase skeletal muscle insulin signal transduction and glucose disposal in GK
      rats. METHODS: DJB was performed in GK rats. Sham operations were performed in GK
      and nondiabetic Wistar-Kyoto (WKY) rats. At 2 weeks post-DJB, oral glucose
      tolerance (OGTT) was measured. At 3 weeks post-DJB, insulin-induced signal
      transduction and glucose disposal were measured in skeletal muscle. RESULTS: In
      GK rats and compared to sham operation, DJB did not (1) improve fasting glucose
      or insulin, (2) improve OGTT, or (3) increase skeletal muscle insulin signal
      transduction or glucose disposal. Interestingly, skeletal muscle glucose disposal
      was similar between WKY-Sham, GK-Sham, and GK-DJB. CONCLUSIONS: Bypassing of the
      proximal small intestine does not increase skeletal muscle glucose disposal. The
      lack of skeletal muscle insulin resistance in GK rats questions whether this
      animal model is adequate to investigate the etiology and treatments for T2DM.
      Additionally, bypassing of the foregut may lead to different findings in other
      animal models of T2DM as well as in T2DM patients.

PMID- 21086063
TI  - Clinical implications of sleeve gastrectomy as a source of spleen infarction or
      ischemia.
AB  - Splenic arterial demarcation has been observed during laparoscopic sleeve
      gastrectomy (LSG). The present study aims to detect its actual incidence during
      LSG and clarify its clinical significance. This is a prospective observational
      study of 287 consecutive patients that underwent LSG by the same surgical team
      over 3 years. In all patients, the gastric fundus was mobilized using a standard
      technique. Before withdrawal of the pneumoperitoneum, the spleen was exposed and
      carefully inspected for evidence of arterial demarcation. Patients with a clear
      demarcation were followed with Doppler ultrasound. Computed tomography scan with
      oral contrast was performed to rule out septic complications. Median preoperative
      body mass index was 46 kg/m(2) (range 35.1-78). Median operative time was 58 min
      (range 42-185), median hospital stay was 3 days (range 3-45), and overall
      morbidity rate was 8.6%. Intraoperative demarcation of the upper splenic pole was
      evident in 12 patients (4.1%). Eleven patients had uneventful postoperative
      course. One patient raised temperature of 38.5 degrees C at the 7th postoperative
      day and was readmitted for further treatment. Once afebrile, the patient was
      discharged on the 10th postoperative day and continued on prophylactic low
      molecular weight heparin (tinzaparin, 7,500 U sc.) for 20 days. Splenic
      discoloration following LSG is an uncommon complication with minimal clinical
      significance, which could be related to hematoma, venous congestion, or ischemia.
      The possibility of a late splenic abscess cannot be ruled out. No risk factors
      can be identified preoperatively.

PMID- 21086064
TI  - Decreased intake of sucrose solutions in orexin knockout mice.
AB  - Orexins are synthesized by lateral hypothalamic neurons and are suggested to be
      implicated in feeding behavior. Recent studies have shown that
      intracerebroventricular administration of orexin-A increases intake of sweet
      tasting solution. Effects of suppressing the orexin system on consumption of
      sweet-tasting solution and sensory processing with sweet taste inputs, however,
      have yet to be examined. We examined the effects of orexin deficiency on sucrose
      solution intake, locomotor activity, and preference for sweet solution using male
      orexin knockout (OxKO) and littermate wild-type (WT) mice. In the dark and over
      24-h periods, OxKO mice showed significantly less sucrose intake and lower
      locomotor activity than WT mice without alteration in food intake whereas
      preferences for 100 mM sucrose were not different between the genotypes.
      Moreover, sucrose intake of OxKO mice was significantly less than sucrose intake
      of a subgroup of WT mice with similar locomotor activity compared to that of OxKO
      mice. These results suggest that factors other than the lower energy expenditure
      due to lower locomotor activity are likely responsible for the decreased sucrose
      intake of OxKO mice. Orexin deficiency may lower the satiety threshold resulting
      in reduced sucrose intake, without altering food intake.

PMID- 21086066
TI  - Intensive insulin therapy in the neurocritical care setting is associated with
      poor clinical outcomes.
AB  - BACKGROUND: Studies devoted to intensive glucose control suggested that the
      intensive insulin therapy (IIT) approach could effectively reduce complications
      associated with critical illness. A program of IIT with the goal of achieving a
      blood glucose of 80-120 mg/dL was, therefore, adopted in this study. To explore
      the impact of this approach in patients admitted to a neurocritical care unit, we
      compared the short-term outcomes of patients treated before and after our policy
      change. METHODS: Retrospectively extracted data from the electronic medical
      records of 1913 patients admitted between Feb 1, 2005 and Aug 30, 2006 were
      included in the standard insulin therapy group (SIT targeted to maintain blood
      glucose levels less than 150 mg/dL) and 1796 patients admitted between Sept 1,
      2006 and March 30, 2008 were included in the IIT group (IIT-targeted to maintain
      blood glucose levels between 80 and 120 mg/dL). RESULTS: Mean glucose levels were
      lower in the IIT compared to SIT (136.9 mg/dL, SD 47.6 vs. 143.8 mg/dL, SD 46.4);
      however, this strategy was also associated with an increased incidence of
      hypoglycemia (OR: 1.8, and 95% CI: 1.5-2.3). The likelihood of mortality
      increased proportionally as the severity of hypoglycemia worsened (any blood
      glucose value <70 mg/dL, OR: 3.26, and 95% CI: 2.52-4.22, any blood glucose <40,
      OR: 3.65, and 95% CI: 2.21-6.02, any blood glucose <20, OR: 6.25, and 95% CI:
      2.41-16.23). CONCLUSION: IIT was not only able to reduce overall mean glucose
      levels, but also resulted in significantly more episodes of hypoglycemia,
      increased mortality, and increased length of stay. The relationship between
      hypoglycemia and mortality indicates that efforts to control glucose levels
      should also aggressively avoid induction of hypoglycemia.

PMID- 21086065
TI  - Astrocytes modulate distribution and neuronal signaling of leptin in the
      hypothalamus of obese A vy mice.
AB  - We tested the hypothesis that astrocytic activity modulates neuronal uptake and
      signaling of leptin in the adult-onset obese agouti viable yellow (A vy) mouse.
      In the immunohistochemical study, A vy mice were pretreated with the astrocyte
      metabolic inhibitor fluorocitrate or phosphate-buffered saline (PBS) vehicle
      intracerebroventricularly (icv) followed 1 h later by Alexa568-leptin. Confocal
      microscopy showed that fluorocitrate pretreatment reduced astrocytic uptake of
      Alexa568-leptin 30 min after icv while increasing neuronal uptake in the arcuate
      nucleus and dorsomedial hypothalamus. Fluorocitrate also induced mild
      astrogliosis and moderately increased pSTAT3 immunopositive neurons in response
      to Alexa568-leptin in the dorsomedial hypothalamus. In the Western blotting
      study, A vy mice were pretreated with either PBS or fluorocitrate, and received
      PBS or leptin 1 h later followed by determination of pSTAT3 and GFAP expression
      an additional 30 min afterward. The results show that fluorocitrate induced a
      mild pSTAT3 activation but attenuated leptin-induced pSTAT3 activation and
      decreased GFAP expression independently of leptin treatment. We conclude that
      inhibition of astrocytic activity resulted in enhanced neuronal leptin uptake and
      signaling. This suggests opposite roles of astrocytes and neurons in leptin's
      actions in the A vy mouse with adult-onset obesity.

PMID- 21086068
TI  - Injection of wild type embryonic stem cells into Mst1 transgenic blastocysts
      prevents adult-onset cardiomyopathy.
AB  - Embryonic stem cells have the capacity to differentiate into a wide range of cell
      types. We previously described that blastocyst injection of wild type (WT)
      embryonic stem cells (ESCs) into various knockout (KO) mouse models of human
      disease prevents disease from occurring. In this study we ask if the blastocyst
      approach can also correct defects in a mouse model of transgenic (Tg)
      overexpression of a pro-apoptotic factor. We injected ROSA26 (LacZ-marked) WT
      ESCs into human mammalian sterile 20 like-kinase 1 (Mst1) Tg blastocysts. Mst1 Tg
      mice overexpress Mst1, a pro-apoptotic factor, in a cardiac-specific manner. As a
      result, Mst1 Tg mice develop adult dilated cardiomyopathy driven by apoptosis,
      reduction in cell density and no hypertrophic compensation. Incorporation of WT
      ESCs generated WT/Mst1 chimeric mice with normal hearts at histological and
      functional levels. Accordingly, apoptosis and cell density parameters were
      normalized. The experiments suggest that an adult-onset cardiac myopathy induced
      by overexpression of the pro-apoptotic Mst1 can be reversed by developmental
      incorporation of WT ESCs. The findings also suggest that since forced expression
      of the Mst1 transgene is not abolished in the rescued chimeras, the WT ES-derived
      cells normalize pathways that lie downstream of Mst1. The results expand the
      therapeutic capability of the ESCs to mouse models that overproduce detrimental
      proteins.

PMID- 21086067
TI  - The role of otx2 in adult mesencephalic-diencephalic dopaminergic neurons.
AB  - Mesencephalic and diencephalic dopaminergic (mdDA) progenitors generate two major
      groups of neurons corresponding to the A9 neurons of the substantia nigra pars
      compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA). MdDA
      neurons control motor, sensorimotor and motivated behaviour and their
      degeneration or abnormal functioning is associated to Parkinson's disease and
      psychiatric disorders. Although relevant advances have been made, the molecular
      basis controlling identity, survival and vulnerability to neurodegeneration of
      SNpc and VTA neurons remains poorly understood. Here, we will review recent
      findings on the role exerted by the transcription factor Otx2 in adult mdDA
      neurons. Otx2 expression is restricted to a relevant fraction of VTA neurons and
      absent in the SNpc. In particular, Otx2 is prevalently excluded from neurons of
      the dorsal-lateral VTA, which expressed Girk2 and high level of the dopamine
      transporter (Dat). Loss and gain of function mouse models revealed that Otx2
      controls neuron subtype identity by antagonizing molecular and functional
      features of the dorsal-lateral VTA such as Girk2 and Dat expression as well as
      vulnerability to the parkinsonian MPTP toxin. Furthermore, when ectopically
      expressed in the SNpc, Otx2 suppresses Dat expression and confers efficient
      neuroprotection to MPTP toxicity by suppressing efficient DA uptake.

PMID- 21086069
TI  - The tissue-specific stem cell as a target for chemoprevention.
AB  - While cancer treatment modalities are gradually improving due to increased
      knowledge about tumor heterogeneity and the cancer stem cell hypothesis, there
      remains a disconnect between tumor detection and mortality rates. The increasing
      knowledge of stem cell biology and its contribution to cancer progression
      illuminates the potential for chemopreventative regimens that effectively target
      the tissue-specific stem cell. Several signaling pathways have emerged that are
      critical for regulating stem cell self-renewal and multilineage differentiation
      over a range of tissue types, including Wnt, Hedgehog, and Notch signaling.
      Dysregulation of these genes can lead to cancer, which supports the cancer stem
      cell hypothesis. Several known chemopreventative agents have recently been shown
      to impact these and other pathways in the stem cell population, suggesting that
      their efficacies may be attributed in part to maintaining homeostasis of tissue
      specific stem cells. Further understanding of the mechanisms of action of
      chemopreventative agents and of stem cell biology will generate better
      chemoprevention regimens that can be recommended especially to those in high-risk
      populations.

PMID- 21086070
TI  - Redefining the concept of standardization for pluripotent stem cells.
AB  - In this report we review the concept of standardization and propose an exhaustive
      framework for the proper management of technology on pluripotent stem cells based
      on studies of global and regional initiatives. We demonstrated detailed
      observational analysis on global initiatives for the standardization of related
      technologies as well as regional attempts with particular interest in the cases
      of the UK, the US and Japan. Consequently, we came up two fundamental issues:
      first, these initiatives and attempts tend to be limited to each of currently
      existing categories of pluripotent stem cells, whereas the technological
      opportunity to enable clinical/commercial application is equally open to all stem
      cell types. Second, the subject to be examined for standardization is set to a
      quite narrow range compared to precedent practices in other industrial sectors.
      To address these issues, we propose a strategic framework for standardization
      with an emphasis on comprehensiveness covering various technological
      opportunities and consistency to learning in the management science. By utilizing
      this framework development of intellectual property rights not only through
      patents but through taking leadership in standardization can be considered as
      means for improving research and development competence. Of particular concerns
      is the formation of quality standards for final products/services and core
      elemental technology, especially specific pluripotent stem cell lines.
      Furthermore, we inferred two stages of the standardization process,
      individualization where a particular product/service is qualified by the market,
      then standardization where the elemental technology is subsequently established
      as compatibility standards.

PMID- 21086071
TI  - Immunological barriers to stem-cell based cardiac repair.
AB  - Repair of damaged myocardium with pluripotent stem cell derived cardiomyocytes is
      becoming increasingly more feasible. Developments in stem cell research emphasize
      the need to address the foreseeable problem of immune rejection following
      transplantation. Pluripotent stem cell (PSC) derived cardiomyocytes have unique
      immune characteristics, some of which are not advantageous for transplantation.
      Here we review the possible mechanisms of PSC-derived cardiomyocytes rejection,
      summarize the current knowledge pertaining to immunogenicity of such cells and
      describe the existing controversies. Myocardial graft rejection can be reduced by
      modifying PSCs prior to their differentiation into cardiomyocytes. Overall, this
      approach facilitates the development of universal donor stem cells suitable for
      the regeneration of many different tissue types.

PMID- 21086072
TI  - Development of Marjolin's ulcer within one month of burn injury with synchronous
      primary lung squamous cell carcinoma in an elderly patient: report of a case with
      allelotyping.
AB  - Marjolin's ulcer defines the occurrence of malignancy, usually squamous cell
      carcinoma, in the setting of a post-traumatic scar often following thermal
      injury. The latency period from the time of injury to the onset of malignant
      transformation averages 30 years with the earliest documented incidence occurring
      6 weeks after injury. In addition, the occurrence of multiple primary
      malignancies is a rare event. To our knowledge, we report the first case in the
      literature of a well-differentiated squamous cell carcinoma developing within 1
      month of thermal injury to an elderly patient's right index finger with an
      incidental synchronous primary lung moderately differentiated squamous cell
      carcinoma that was morphologically and genetically different as confirmed by
      allelotyping. There is scant precedent literature on acute Marjolin's ulcers, and
      the most acute cases have arisen 6 weeks post-burn. There is also little
      published literature on the incidence of multiple primary malignancies. The
      quoted incidence of this event is <1%. Clinicians should be aware of the
      possibility of malignant transformation at the site of prior thermal injury.
      Biopsy remains the gold standard for diagnosis for Marjolin's ulcer. MRI is the
      most important diagnostic imaging tool because it will demonstrate the margins
      and extent of the lesion. Due to the aggressive nature of Marjolin's ulcer,
      treatment is usually surgical and dependent upon grading. When multiple lesions
      are detected after staging of a presumed neoplasm, the possibility of multiple
      primary maligancies should be considered. Allelotyping is a process that can be
      utilized to determine if multiple masses are related.

PMID- 21086073
TI  - Poor efficacy of BEP polychemotherapy in metastatic spermatocytic seminoma.
AB  - Metastatic spermatocytic seminoma is an extremely rare disease. No
      chemotherapeutic regimen is established and the use of adjuvant radiation therapy
      after orchiectomy as frequently performed for classical seminoma is unclear. We
      report the third case of proven spermatocytic seminoma metastatic in the
      literature and provide a review of the literature. Administering BEP
      polychemotherapy as in classical seminoma was poorly effective in reducing the
      retroperitoneal mass in a patient with spermatocytic seminoma. A review of the
      literature showed that all the three described patients developing metastatic
      disease did not receive adjuvant radiation therapy after orchiectomy, which might
      be considered in high-risk cases.

PMID- 21086074
TI  - Stroke prevention treatment of patients with atrial fibrillation: old and new.
AB  - Atrial fibrillation is the most common cause of cardioembolic ischemic stroke and
      has a rising prevalence worldwide. Stroke prevention in this condition is poised
      to take a substantial leap forward with the evolution of new anticoagulant
      medications, with superior properties compared to vitamin K antagonists. New,
      safer and more effective chronic therapy is on the horizon. However, many issues
      surrounding the management of stroke prevention after an acute stroke and during
      the course of chronic anticoagulant therapy remain to be resolved.

PMID- 21086075
TI  - Combination lipid therapy in type 2 diabetes.

PMID- 21086077
TI  - 1H, 13C, and 15N resonance assignments of reduced GrxS14 from Populus tremula *
      tremuloides.
AB  - GrxS14 is a monothiol Glutaredoxin (Grx) from Populus tremula * tremuloides,
      which has a CGFS active site. GrxS14 is located in the chloroplasts and has been
      found to occur ether as an apo form or as a holo form with a [2Fe-2S] cluster.
      The holo form contains two monomers of apo GrxS14 bridged by the iron sulphur
      center, in the presence of two external glutathione molecules (Bandyopadhyay et
      al. 2008). The NMR assignments of the GrxS14 are essential for its solution
      structure determination.

PMID- 21086076
TI  - Update on the prevention of type 2 diabetes.
AB  - Diabetes has emerged as the modern day epidemic that is currently affecting over
      220 million people worldwide and claiming at least 1.1 million lives in 2005
      alone. The rise in diabetes is largely attributed to the epidemic of obesity
      together with sedentary lifestyle as well as unhealthy dietary habits. Despite
      evidence that glycemic control as well as control of other cardiovascular disease
      (CVD) risk factors such as hypertension and dyslipidemia decreases morbidity and
      mortality in the diabetic population, control of glycemia and other CVD risk
      factors remains largely suboptimal making the concept of prevention of diabetes
      very appealing to control CVD risk, especially that such a risk is already
      increased in people in the prediabetic stage. Several large controlled trials
      have been completed testing various options for diabetes prevention. In this
      paper we present an update on prevention of type 2 diabetes highlighting the
      major recent trials completed to date in this very important area of
      investigation.

PMID- 21086078
TI  - Intensified Lipid-Lowering Therapy in Coronary Heart Disease: Is the Concept of
      "the Lower the Better" Evidence Based?

PMID- 21086079
TI  - Recognition and management of sleep-disordered breathing in chronic heart
      failure.
AB  - It is increasingly recognized that sleep-disordered breathing (SDB) is a common
      modifiable risk factor for cardiovascular disease with significant impact on
      morbidity and potentially mortality. SDB is highly prevalent in patients with
      systolic or diastolic heart failure. A high index of suspicion is necessary to
      diagnose SDB in patients with heart failure because the vast majority of affected
      patients do not report daytime symptoms. Recent clinical trials have demonstrated
      improvement in heart function, exercise tolerance, and quality of life after
      treatment of SDB in patients with heart failure. Accumulating evidence suggests
      that treatment of SDB should complement the established pharmacologic therapy for
      chronic heart failure. However, mortality benefit has yet to be demonstrated.

PMID- 21086080
TI  - Number crunching: how and when will numerical models be used in the clinical
      setting?

PMID- 21086081
TI  - Imatinib and the treatment of fibrosis: recent trials and tribulations.
AB  - Imatinib mesylate has become a therapy of interest for the treatment of systemic
      sclerosis because of its ability to inhibit c-Abl and platelet-derived growth
      factor receptor, tyrosine kinases involved in profibrotic pathways. Preclinical
      data using in vitro and murine models of fibrosis have demonstrated the
      antifibrotic properties of imatinib. Imatinib is currently used widely in the
      treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and
      other conditions, and a large amount of information is available regarding the
      safety of the medication in these patient populations. Whether imatinib will be
      tolerable or effective in the treatment of systemic sclerosis is the subject of
      several investigations. The aim of this review is to summarize this body of
      research to date.

PMID- 21086082
TI  - MR and US imaging for breast cancer patients who underwent conservation surgery
      after neoadjuvant chemotherapy: comparison of triple negative breast cancer and
      other intrinsic subtypes.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly utilized to treat operable
      breast cancer. The purpose of this study was to review the findings of
      ultrasonography (US) and magnetic resonance (MR) imaging in patients treated with
      breast conservation surgery (BCS) after NAC with a focus on intrinsic subtypes.
      METHODS: Eighty-six patients underwent BCS after NAC. The tumors were classified
      into four subgroups by receptor status. US and MR were performed before and after
      NAC. The tumor diameters in US and MR after NAC were examined for correlations
      with pathological tumor distances in the specimens from BCS after NAC. RESULTS:
      The correlation coefficient (r) of US to pathological tumor size was 0.3 in all
      tumors, 0.6 in HER2-type tumors, and 0.7 in triple negative breast cancers
      (TNBC). The correlation coefficient of tumor size in MR to pathological tumor
      size was 0.9 in TNBC, and other correlations were not statistically significant.
      CONCLUSIONS: The correlation between tumor size in MR and pathological tumor size
      in triple negative breast cancers corresponded best. This information is one of
      the clues to selecting patients for BCS after NAC.

PMID- 21086083
TI  - Response surface methodology to optimize novel fast disintegrating tablets using
      beta cyclodextrin as diluent.
AB  - The objective of this work was to apply response surface approach to investigate
      main and interaction effects of formulation parameters in optimizing novel fast
      disintegrating tablet formulation using beta cyclodextrin as a diluent. The
      variables studied were diluent (beta cyclodextrin, X (1)), superdisintegrant
      (Croscarmellose sodium, X (2)), and direct compression aid (Spray dried lactose,
      X (3)). Tablets were prepared by direct compression method on B2 rotary tablet
      press using flat plain-face punches and characterized for weight variation,
      thickness, disintegration time (Y (1)), and hardness (Y (2)). Disintegration time
      was strongly affected by quadratic terms of beta cyclodextrin, croscarmellose
      sodium, and spray-dried lactose. The positive value of regression coefficient for
      beta cyclodextrin suggested that hardness increased with increased amount of beta
      cyclodextrin. In general, disintegration of tablets has been reported to slow
      down with increase in hardness. However in the present study, higher
      concentration of beta cyclodextrin was found to improve tablet hardness without
      increasing the disintegration time. Thus, beta cyclodextrin is proposed as a
      suitable diluent to achieve fast disintegrating tablets with sufficient hardness.
      Good correlation between the predicted values and experimental data of the
      optimized formulation validated prognostic ability of response surface
      methodology in optimizing fast disintegrating tablets using beta cyclodextrin as
      a diluent.

PMID- 21086084
TI  - Inter- and intra-manufacturer variability in pharmaceutical grades and lots of
      xanthan gum.
AB  - A pharmaceutical formulation typically contains one or more excipients in
      addition to the active pharmaceutical ingredient(s). Though excipients have been
      considered inert components of a formulation, variability in their properties has
      been shown to affect the performance of drug dosage forms and delivery systems.
      This study investigates the inter- and intra-manufacturer variability among
      different NF grades and lots of xanthan gum made by two manufacturers. As many
      formulators rely on compendial standards to monitor and control the variability
      of excipients, this study focuses on the adequacy of the NF specifications, in
      particular the viscosity specification, to discern the variability in solution
      properties of different pharmaceutical grades and lots of xanthan gum. All the
      grades and lots in this study were NF grade materials. Xanthan gum solutions were
      prepared in accordance with NF test methodology and were rheologically evaluated
      using a rotational rheometer. Both steady shear measurements and small amplitude
      oscillatory measurements were carried out on 1% w/w xanthan gum solutions.
      Results showed significant inter- and intra-manufacturer variability among the NF
      grades and lots of xanthan gum that was not reflected in the NF viscosity test
      specifications.

PMID- 21086085
TI  - CREON (Pancrelipase Delayed-Release Capsules) for the treatment of exocrine
      pancreatic insufficiency.
AB  - Exocrine pancreatic insufficiency (EPI) is associated with conditions including
      cystic fibrosis (CF), chronic pancreatitis (CP), and pancreatic surgery (PS). The
      symptoms include maldigestion, malnutrition, weight loss, flatulence, and
      steatorrhea. Pancreatic enzyme replacement therapy (PERT) is the standard
      treatment for EPI; it is regulated in many countries and most recently in the USA
      following a US FDA mandate for all PERT manufacturers to submit new drug
      applications. Pancrelipase delayed-release capsules (CREON(r), Abbott, Marietta,
      GA, USA) have been available in Europe since 1984 and in the USA since 1987; a
      new formulation was the first PERT to gain approval in the USA in 2009. The
      efficacy and safety of CREON have been demonstrated in double-blind, randomized,
      placebo-controlled trials in patients with CF aged >=7 years and in patients with
      CP or post-PS. The data consistently demonstrate significantly better fat and
      nitrogen absorption with CREON versus placebo, and improvements in clinical
      symptoms, stool frequency, and body weight. Additionally, efficacy and safety of
      CREON have been shown in open-label studies in young children with CF (aged 1
      month to 6 years), with control of fat malabsorption and control of clinical
      symptoms. The most commonly reported adverse events (AEs) with PERT are
      gastrointestinal disorders and allergic skin reactions. In clinical studies,
      CREON was well tolerated with very few withdrawals due to AEs and a low frequency
      of AEs judged treatment related, regardless of patient age. To further support
      the known safety profile of PERT, all manufacturers are required to investigate
      risk factors for fibrosing colonopathy, a rare gastrointestinal complication of
      CF, and the theoretical risk of viral transmission from porcine-derived PERT
      products. Together, the clinical study data and wealth of clinical experience
      suggest that CREON is effective and safe in patients with EPI regardless of
      etiology, with a very favorable risk-benefit profile.

PMID- 21086086
TI  - Older persons with diabetes receive fewer inappropriate ICD shocks: results from
      the INTRINSIC RV trial.
AB  - In patients with heart disease, diabetes and age predict adverse outcomes. It
      remains unclear whether persons with diabetes who have implantable cardioverter
      defibrillators (ICDs) have fewer appropriate and inappropriate ICD shocks. The
      objective of this study is to determine if persons with diabetes who have ICDs
      receive a similar amount of appropriate and inappropriate shocks compared to
      persons without diabetes. In a post hoc analysis of 1,528 patients enrolled in
      the INTRINSIC RV trial, all-cause mortality and ICD shocks between persons with
      and without diabetes, stratified by age, was compared. The relationship between
      shock and mortality was also assessed. Mortality 1 year after ICD implant was
      lower for persons without diabetes vs. persons with diabetes (3.5% vs. 7.9%, p <
      0.001). Young and old persons with diabetes received a similar number of total
      and appropriate ICD shocks. However, older persons with diabetes were less likely
      to receive inappropriate ICD shocks vs. older persons without diabetes (1.9% vs.
      6.9%, p < 0.01). ICD shocks were not temporally related to mortality regardless
      of diabetes status. In the INTRINSIC RV trial, persons with diabetes and older
      persons without diabetes undergoing ICD implant were at a higher risk of death.
      Older persons with diabetes received less inappropriate shocks and still had a
      similar amount of appropriate shocks compared to persons without diabetes of
      similar age.

PMID- 21086087
TI  - External fixation in pelvic fractures.
AB  - Pelvic fractures account for 4-5% of all fracturated patients, and they occur in
      4-5% of polytraumatized patients. In the most of the cases, they are consequent
      to high-energy trauma with a high percentage of lesions of other organs
      (cerebral, thoracic, and abdominal lesions. The most of the patients (80%) who
      die are dying within the first hours after trauma for a massive hemorrhagic
      shock. When the pelvic fracture and the patient's hemodynamic conditions are both
      unstable, osteosynthesis of the fracture is mandatory. Fracture stabilization
      should be performed within the first hour after trauma (as soon as possible), and
      it should be considered as part of the resuscitation procedure. We usually make
      an urgent stabilization of pelvic fracture with an anterior external fixator
      technique. We have revised all unstable pelvic fractures treated in our
      department (Orthopaedic Clinic Pisa University) from 2000 up to the 2005 to
      determine a correct treatment protocol for these lesions. Pelvic stabilization,
      reducing the pelvic volume and bleeding from the stumps of fracture, determines
      the arrest of the hemorrhage, as evidenced by the sharp decline in the number of
      transfusions in postoperative period. In these cases, there is an absolute
      indication for an urgent pelvic stabilization. Pelvic stabilization, whether
      temporary or permanent, allows to control the bleeding because it (1) leads to a
      reduction in the volume pelvis with a containment on the retro-peritoneal
      hematoma (2) reduces bleeding from the fracture fragments (3) reduces motility
      fracture promoting the blood clotting. The stabilization of the pelvis also makes
      it easier to manage the patient and his mobilization for the implementation of
      subsequent investigations. In our experience, external fixator accounts for its
      characteristics the gold standard approach for the urgent stabilization of these
      lesions, and, for most of them, it can be used as the definitive treatment.
      External fixation is a quick and easy procedure for pelvic fractures
      stabilization for surgeons with experience with this technique.

PMID- 21086088
TI  - Prevalence of undernutrition among Kora-Mudi children aged 2-13 years in Paschim
      Medinipur District, West Bengal, India.
AB  - BACKGROUND: nutritional status of tribal children in West Bengal has not been
      investigated adequately. The present study was undertaken to determine the
      prevalence of underweight, stunting and wasting in Kora-Mudi children of Paschim
      Medinipur, West Bengal, India. METHODS: a cross sectional study was undertaken in
      two villages of the Paschim Medinipur District. Of 119 children aged 2-13 years,
      59 boys and 60 girls were studied. Height and weight measurements were made by
      standard techniques. Children were considered as underweight, stunting and
      wasting if their weight-for-age, height-for-age and weight-for-height Z-scores <
      2.0 SD of the National Center for Health Statistics reference standards. RESULTS:
      the overall prevalence of underweight, stunting and wasting was 52.9%, 49.6% and
      22.7%, respectively. About 16.0%, 24.4% and 1.7% of children were found to be
      severely underweight, stunted and wasted. The prevalence of underweight, stunting
      and wasting was higher in preschool children than in school going children. The
      chance of underweight, stunting and wasting was 1.80, 1.10 and 1.58 times greater
      in preschool children than in school going children. Moreover, the prevalence of
      underweight, stunting and wasting was higher in boys than in girls. The boys had
      1.45, 1.66 and 2.02 times greater risk to be underweight, stunted and wasted.
      According to the WHO classification of severity in malnutrition, the overall
      prevalence of underweight, stunting and wasting was as high as >= 30%, >= 40 and
      >= 15%. CONCLUSIONS: the nutritional status of Kora-Mudi children in West Bengal
      is critical. Appropriate measures should be taken by the respective authorities
      to improve childhood health and nutritional status.

PMID- 21086090
TI  - A superficial colon tumor model involving subcutaneous colon translocation and
      orthotopic transplantation of green fluorescent protein-expressing human colon
      tumor.
AB  - The orthotopic transplantation model of human tumor has been demonstrated to be
      more patient-like animal tumor model. However, observations of tumor progression
      and metastasis are limited by the deep location of the colon or limited deep
      penetration ability of fluorescence through tissue. The purpose of this study is
      to establish a superficial orthotopic model to allow easier real-time
      visualization and more sensitive monitoring of fluorescent orthotopic colon
      tumor. Human colon cancer HT-29 cells were transduced with a pLPCX expression
      retroviral vector containing green fluorescent protein and neomycin resistance
      genes. For superficial orthotopic transplantation model, the cecum was identified
      and pulled out of the peritoneal cavity, the space between the cecum and
      peritoneum was sutured, the cecum was pulled to subcutaneous tissue, and incision
      was made on the cecal serosa followed by the implantation of a 1-mm tumor tissue
      to the cecum. For comparison, a conventional orthotopic transplantation model was
      established in a separate group of mice simultaneously. When tumor sizes reached
      5 mm in diameter, half the mice in each model received 5-FU treatment. Primary
      tumor and metastases were monitored by fluorescent imaging or caliber
      measurement. Tumor fluorescence was observed as early as 3 days (median time of
      4.7 +/- 1.3 days) post-transplantation in the superficial orthotopic
      transplantation model, which was much earlier than 21 days (median time of 26.2
      +/- 9.9 days) in conventional orthotopic transplantation model. Although tumor
      growth of 5-FU-treated mice in conventional orthotopic model was lower than those
      of the untreated mice, the difference was not significant. However, in
      superficial orthotopic model, tumor growth was significantly inhibited in 5-FU
      treated mice relative to the untreated mice. Fluorescence imaging showed similar
      metastasis incidence between the superficial and conventional orthotopic
      transplantation models. The fluorescent superficial orthotopic transplantation
      colon model allows easier real-time visualization and more sensitive monitoring
      of tumor growth as well as convenient repeated sampling. It is a valuable
      orthotopic implantation model for study of colon cancer and evaluation of new
      anti-cancer therapy.

PMID- 21086091
TI  - Prognostic and predictive values of pERK1/2 and pAkt-1 expression in non-small
      cell lung cancer patients treated with adjuvant chemotherapy.
AB  - Ras/ERK and PI3K/Akt pathways are reported to play a prognostic role and
      contribute to drug resistance in many cancers. The objective of this study was to
      explore associations between the expression levels of several molecules in
      Ras/ERK and PI3K/Akt pathways and their clinical significance in predicting the
      effectiveness of postoperative adjuvant chemotherapy in patients with non-small
      cell lung cancer (NSCLC). The expressions of K-ras, Raf-1, ERK1/2, phosphorylated
      ERK1/2 (pERK1/2), Akt-1, phosphorylated Akt-1 (pAkt-1), and Bcl-2 were detected
      by immunohistochemistry in tumor specimens from 144 NSCLC patients. The
      correlations between the expression levels of these molecules and the
      clinicopathological characteristics were analyzed. Patient survival was analyzed
      by Kaplan-Meier method, log-rank test, and Cox regression. The positive
      expression rates of K-ras, Raf-1, ERK1/2, pERK1/2, Akt-1, pAkt-1, and Bcl-2 were
      21.5%, 41.7%, 59.7%, 27.1%, 50.7%, 36.1%, and 30.6%, respectively. Univariate
      analysis showed that patients with pERK1/2-positive (P = 0.01), Bcl-2-positive (P
      = 0.023), or pAkt-1 negative (P = 0.021) had significantly better recurrence-free
      survival (RFS) than those with pERK1/2-negative, Bcl-2-negative, or pAkt-1
      positive. Multivariate analysis showed that earlier stage (P <= 0.001), non
      adenocarcinoma (P <= 0.001), pERK1/2-positive (P <= 0.001), and pAkt-1-negative
      (P = 0.016) were independent prognostic factors for a better RFS in NSCLC.
      pERK1/2-positive and pAkt-1-negative proved to contribute to a better RFS in
      postoperative NSCLC patients who received adjuvant chemotherapy after taking the
      stage and histological subtype into account. pERK1/2 and pAkt-1 could be
      considered as new independent prognostic biomarkers for predicting RFS and
      selecting patients who are more likely to benefit from postoperative adjuvant
      chemotherapy.

PMID- 21086095
TI  - Conference on the 100th birthday anniversary of Ivan Malek (1909-1994); Prague,
      15-16 October 2009. Introduction.

PMID- 21086092
TI  - Expression of C-reactive protein and cyclooxygenase enzyme-2 in clear cell renal
      cell carcinoma: correlation with pathological parameters in 110 patients.
AB  - C-reactive protein is produced in response to cytokines such as interleukin (IL)
      6. It is known that increased plasma IL-6 levels induce increased hepatic and
      intratumoral production of C-reactive protein. Cyclooxygenase enzyme-2 is induced
      by various stimuli, including inflammation and various growth factors. Expression
      of these two markers has not been well studied in clear cell renal cell
      carcinoma. The objective of this study is to correlate the expression of C
      reactive protein and cyclooxygenase enzyme-2 in clear cell renal cell carcinoma
      with pathologic parameters. A search of the surgical pathology and consultation
      files at our institution was performed for nephrectomy specimens with clear cell
      renal cell carcinoma from 2007 to 2008. Immunohistochemical stains for C-reactive
      protein and cyclooxygenase enzyme-2 were performed. Staining intensity was graded
      as 0, 1+, 2+, and 3+. The staining intensity was then correlated with pathologic
      stage and Fuhrman nuclear grade for each case. A total of 110 cases were
      identified. Strong expression of C-reactive protein was associated with higher
      Fuhrman nuclear grade and pathologic stage, and the strength of correlation was
      statistically significant (p = 0.01 and p = 0.001), respectively. However,
      cyclooxygenase enzyme-2 expression did not show statistically significant
      correlation with both pathologic stage and Fuhrman nuclear grade (p = 0.1 and p =
      0.15), respectively. To our knowledge, this is the largest study to date
      correlating the expression of both C-reactive protein and cyclooxygenase enzyme-2
      in tissue with pathologic parameters in patients with clear cell renal cell
      carcinoma, which could have significant prognostic and therapeutic implications.

PMID- 21086096
TI  - Memories of a great man, Ivan Malek.

PMID- 21086097
TI  - Ivan Malek and the Institute of Microbiology.

PMID- 21086099
TI  - Do we need new antibiotics? The search for new targets and new compounds.
AB  - Resistance to antibiotics and other antimicrobial compounds continues to
      increase. There are several possibilities for protection against pathogenic
      microorganisms, for instance, preparation of new vaccines against resistant
      bacterial strains, use of specific bacteriophages, and searching for new
      antibiotics. The antibiotic search includes: (1) looking for new antibiotics from
      nontraditional or less traditional sources, (2) sequencing microbial genomes with
      the aim of finding genes specifying biosynthesis of antibiotics, (3) analyzing
      DNA from the environment (metagenomics), (4) re-examining forgotten natural
      compounds and products of their transformations, and (5) investigating new
      antibiotic targets in pathogenic bacteria.

PMID- 21086100
TI  - The impact of Ivan Malek's continuous culture concept on bioprocessing.
AB  - This paper summarizes research results and their industrial applications obtained
      by continuous culture in the former Czechoslovakia. Past achievements as well as
      recent trends and developments worldwide are presented. The term "Prague School
      of continuous culture" is put forward and its international activity is outlined.
      The impact of this school was pervasive across the entire field of applied
      microbiology and biotechnology in Czechoslovakia and, perhaps, even beyond the
      country's borders. Continuous culture is a very mature field, and since its
      establishment it has become a powerful research tool. The present activity in
      this field amounts to a renaissance of continuous culture, emphasizing new
      dimensions in bioinformatics and systems biology.

PMID- 21086098
TI  - General and molecular microbiology and microbial genetics in the IM CAS.
AB  - This review summarizes the main results obtained in the fields of general and
      molecular microbiology and microbial genetics at the Institute of Microbiology of
      the Academy of Sciences of the Czech Republic (AS CR) [formerly Czechoslovak
      Academy of Sciences (CAS)] over more than 50 years. Contribution of the founder
      of the Institute, academician Ivan Malek, to the introduction of these topics
      into the scientific program of the Institute of Microbiology and to further
      development of these studies is also included.

PMID- 21086101
TI  - Chemostat-induced uneven division of Bacillus subtilis.
AB  - Anomalous forms of Bacillus subtilis A32 produced by prolonged cultivation in a
      chemostat under nitrogen limitation are described. A change in the cultivation
      conditions brought about a transformation of these forms to bacillar rods. The
      transformation was gradual and lasted for several generations.

PMID- 21086102
TI  - Biofiltration of paint solvent mixtures in two reactor types: overloading by
      hydrophobic components.
AB  - Steady-state performance characteristics of a trickle bed reactor (TBR) and a
      biofilter (BF) in loading experiments with increasing toluene/xylenes inlet
      concentrations while maintaining a constant loading rate of hydrophilic
      components (methyl ethyl and methyl isobutyl ketones, acetone, and n-butyl
      acetate) of 4 g m-3 h-1 were evaluated and compared, along with the systems'
      dynamic responses. At the same combined substrate loading of 55 g m-3 h-1 for
      both reactors, the TBR achieved more than 1.5 times higher overall removal
      efficiency (RE(W)) than the BF. Increasing the loading rate of aromatics resulted
      in a gradual decrease of their REs. The degradation rates of acetone and n-butyl
      acetate were also inhibited at higher loads of aromatics, thus revealing a
      competition in cell catabolism. A step-drop in loading of aromatics resulted in
      an immediate increase of RE(W) with variations in the TBR, while the new steady
      state value in the BF took 6-7 h to achieve. The TBR consistently showed a
      greater performance than BF in removing toluene and xylenes. Increasing the
      loading rate of aromatics resulted in a gradual decrease of their REs. The
      degradation rates of acetone and n-butyl acetate were also lower at higher
      OL(AROM), revealing a competition in the cell catabolism. The results obtained
      are consistent with the proposed hypothesis of greater toxic effects under low
      water content, i.e., in the biofilter, caused by aromatic hydrocarbons in the
      presence of polar ketones and esters, which may improve the hydrocarbon
      partitioning into the aqueous phase.

PMID- 21086103
TI  - Microbial lipids from renewable resources: production and characterization.
AB  - A number of microorganisms belonging to the genera of algae, yeast, bacteria, and
      fungi have ability to accumulate neutral lipids under specific cultivation
      conditions. The microbial lipids contain high fractions of polyunsaturated fatty
      acids and have the potential to serve as a source of significant quantities of
      transportation fuels. This paper reviews the current state of the art of this
      field. It summarizes the various microorganism used, feed stocks available,
      environmental factors that influence growth of cells and accumulation of lipids,
      major fatty acid composition of lipids, and the technology.

PMID- 21086104
TI  - Development of soil microbiology methods: from respirometry to molecular
      approaches.
AB  - This review deals with techniques and methods used in the study of the function
      and development of microorganisms occurring in soil with emphasis on the
      contributions of Czech Academician Ivan Malek and his coworkers or fellows (Jiri
      Macura, Frantisek Kunc) to the development of basic techniques used in soil
      microbiology. Early studies, including batch cultivation and respirometric
      techniques, as well as later developments of percolation and continuous-flow
      methods of cultivation of soil microorganisms are discussed. Recent developments
      in the application of analytical chemistry (HPLC or GC) and of molecular
      biological techniques to ecological questions that have revolutionized concepts
      in soil microbiology and microbial ecology are also briefly mentioned, including
      denaturing gradient gel electrophoresis (DGGE), temperature gradient gel
      electrophoresis (TGGE), phospholipid fatty acid analysis (PLFA) and others. The
      shift of soil microbiology from the study of individual microorganisms to entire
      microbial communities, including nonculturable species, is briefly discussed.

PMID- 21086105
TI  - Wetlands as energy-dissipating systems.
AB  - Since wetlands are ecosystems that have an ample supply of water, they play an
      important role in the energy budgets of their respective landscapes due to their
      capacity to shift energy fluxes in favor of latent heat. Rates of
      evapotranspiration in wetlands are commonly as high as 6-15 mm day-1, testifying
      to the large amount of energy that is dissipated through this process. Emergent
      or semi-emergent wetland macrophytes substantially influence the solar energy
      distribution due to their high capacity for transpiration. Wetland ecosystems in
      eutrophic habitats show a high primary production of biomass because of the
      highly efficient use of solar energy in photosynthesis. In wetlands associated
      with the slow decomposition of dead organic matter, such as oligotrophic marshes
      or fens and bogs, the accumulation of biomass is also high, in spite of the
      rather low primary production of biomass. Most of the energy exchange in water
      saturated wetlands is, however, linked with heat balance, whereby the largest
      proportion of the incoming energy is dissipated during the process of
      evapotranspiration. An example is shown of energy fluxes during the course of a
      day in the wetland ecosystem of Mokre Louky (Wet Meadows) near Trebon. The
      negative consequences of the loss of wetlands for the local and regional climate
      are discussed.

PMID- 21086106
TI  - The development of microalgal biotechnology in the Czech Republic.
AB  - Microscopic algae and cyanobacteria are excellent sources of numerous compounds,
      from raw biomass rich in proteins, oils, and antioxidants to valuable secondary
      metabolites with potential medical use. In the former Czechoslovakia, microalgal
      biotechnology developed rapidly in the 1960s with the main aim of providing
      industrial, high-yield sources of algal biomass. Unique cultivation techniques
      that are still in use were successfully developed and tested. Gradually, the
      focus changed from bulk production to more sophisticated use of microalgae,
      including production of bioactive compounds. Along the way, better understanding
      of the physiology and cell biology of productive microalgal strains was achieved.
      Currently, microalgae are in the focus again, mostly as possible sources of
      bioactive compounds and next-generation biofuels for the 21st century.

PMID- 21086107
TI  - Experimental validation of a nonequilibrium model of CO2 fluxes between gas,
      liquid medium, and algae in a flat-panel photobioreactor.
AB  - Carbon dioxide (CO2) availability strongly affects the productivity of algal
      photobioreactors, where it is dynamically exchanged between different
      compartments, phases, and chemical forms. To understand the underlying processes,
      we constructed a nonequilibrium mathematical model of CO2 dynamics in a flat
      panel algal photobioreactor. The model includes mass transfer to the algal
      suspension from a stream of bubbles of CO2-enriched air and from the
      photobioreactor headspace. Also included are the hydration of dissolved CO2 to
      bicarbonate ion (HCO3-) as well as uptake and/or cycling of these two chemical
      forms by the cells. The model was validated in experiments using a laboratory
      scale flat-panel photobioreactor that controls light, temperature, and pH and
      where the concentration of dissolved CO2, and partial pressure of CO2 in the
      photobioreactor exhaust are measured. First, the model prediction was compared
      with measured CO2 dynamics that occurred in response to a stepwise change in the
      CO2 partial pressure in the gas sparger. Furthermore, the model was used to
      predict CO2 dynamics in photobioreactors with unicellular, nitrogen-fixing
      cyanobacterium Cyanothece sp. The metabolism changes dramatically during a day,
      and the distribution of CO2 is expected to exhibit a pronounced diurnal
      modulation that significantly deviates from chemical equilibrium.

PMID- 21086109
TI  - [Total elbow joint arthroplasty. Surgical approaches].
AB  - The dorsal approach to the elbow joint is commonly used for arthroplasty of the
      joint and consists of different steps. The superficial approach including the
      incision of the skin and the preparation of subcutaneous tissue precedes the deep
      approach. The latter contains preparation and transposition of the ulnar nerve,
      relief of extensors and ligaments radiating into the articular capsule.
      Concerning the preparation of the extensors three important techniques are
      differentiated, triceps splitting, triceps reflecting and triceps preserving.

PMID- 21086108
TI  - LAG-3 in Cancer Immunotherapy.
AB  - LAG-3 (CD223) is a cell surface molecule expressed on activated T cells (Huard et
      al. Immunogenetics 39:213-217, 1994), NK cells (Triebel et al. J Exp Med 171:1393
      1405, 1990), B cells (Kisielow et al. Eur J Immunol 35:2081-2088, 2005), and
      plasmacytoid dendritic cells (Workman et al. J Immunol 182:1885-1891, 2009) that
      plays an important but incompletely understood role in the function of these
      lymphocyte subsets. In addition, the interaction between LAG-3 and its major
      ligand, Class II MHC, is thought to play a role in modulating dendritic cell
      function (Andreae et al. J Immunol 168:3874-3880, 2002). Recent preclinical
      studies have documented a role for LAG-3 in CD8 T cell exhaustion (Blackburn et
      al. Nat Immunol 10:29-37, 2009), and blockade of the LAG-3/Class II interaction
      using a LAG-3 Ig fusion protein is being evaluated in a number of clinical trials
      in cancer patients. In this review, we will first discuss the basic structural
      and functional biology of LAG-3, followed by a review of preclinical and clinical
      data pertinent to a role for LAG-3 in cancer immunotherapy.

PMID- 21086110
TI  - [Endoprosthetics of the radial column after trauma].
AB  - Non-displaced fractures of the radius head are in most cases treated
      conservatively. Open reduction and anatomical internal fixation of displaced
      radius head fractures is the method of choice. In comminuted fractures of the
      radius head (Mason type III and type IV) replacement with a radius head
      prosthesis achieves joint stability and prevents secondary complications, such as
      valgus elbow deformity and proximal radial migration. Modern anatomically formed
      prostheses show promising results in the medium-term view. Typical complications
      after radius head replacement are limited range of motion in the elbow joint,
      arthritis of the capitulum and heterotopic ossifications. In cases of capitulum
      arthritis, capitulum prostheses were developed to resurface the lateral
      compartment of the elbow joint. Short-term results are encouraging with
      improvements in pain and range of movement.

PMID- 21086111
TI  - [Endoprosthesis for the fractured elbow: uni- and bicompartmental
      alloarthroplasty of the humero-ulnar joint].
AB  - Posttraumatic arthrosis or rheumatoid arthritis located at the elbow, in
      particular at the humero-ulnar joint will probably not occur in increasing
      numbers in the future due to new antirheumatic medications and modern implants.
      However, the demographic development with an increase of the geriatric population
      and the typical physical changes is evident. Due to osteoporosis with a resulting
      poor bone quality severe fracture patterns may occur at the site of the distal
      humerus after a simple collapse. The usual surgical aim consisting of an exact
      anatomic reduction may be impossible to achieve by applying the standard
      operative treatment. Several studies have proven that a prosthetic replacement of
      such a severely damaged elbow is a viable solution for elderly people. A mobile,
      pain-free and stable elbow joint promotes a fast recovery of the patient with a
      quick return to former activities. Nevertheless, elbow prostheses cannot
      withstand great strains and the surgeon has to identify those fractures which
      require a prosthetic replacement. The surgical implantation procedure requires an
      adequate knowledge of both elbow anatomy and prosthetic options.

PMID- 21086112
TI  - Short-term survival by treatment among patients hospitalized with acute heart
      failure: the global ALARM-HF registry using propensity scoring methods.
AB  - PURPOSE: To date, treatment with intravenous (IV) agents such as vasodilators,
      diuretics, and inotropes has shown marginal or mixed benefits in acute heart
      failure (AHF) trials. The aim of this study was to identify the risks and
      benefits of IV drugs in patients hospitalized with acute decompensated heart
      failure. METHODS: The AHF global survey of standard treatment (ALARM-HF) reviewed
      in-hospital treatments in eight countries. The present study was a post hoc
      analysis of ALARM-HF data in which propensity scoring was used to identify groups
      of patients who differed by treatment but had the same multivariate distribution
      of covariates. Such propensity matching allowed estimations of the effect of
      specific treatments on the outcome of in-hospital mortality. RESULTS: Unadjusted
      analysis showed a lower in-hospital mortality rate in AHF patients receiving
      "diuretics + vasodilators" (n = 1,805) compared to those receiving "diuretics
      alone" (n = 2,362) (7.6 vs. 14.2%, p < 0.0001). Propensity-based matching (n =
      1,007 matched pairs) confirmed the lower mortality of AHF patients receiving
      diuretics + vasodilators: 7.8 versus 11.0% (p = 0.016). Unadjusted analysis
      showed a much greater in-hospital mortality rate in patients receiving IV
      inotropes (25.9%) compared to those who did not (5.2%) (p < 0.0001). Propensity
      based matching (n = 954 pairs) confirmed that IV catecholamine use was associated
      with 1.5-fold increase for dopamine or dobutamine use and a >2.5-fold increase
      for norepinephrine or epinephrine use. CONCLUSIONS: In terms of in-hospital
      survival, a vasodilator in combination with a diuretic fared better than
      treatment with only a diuretic. Catecholamine inotropes should be used cautiously
      as it has been seen that they actually increase the risk for in-hospital
      mortality.

PMID- 21086113
TI  - Cardiogenic shock and nutrition: safe?
AB  - Cardiogenic shock is a common diagnosis in patients in the intensive care unit
      (ICU), and is characterized by a decreased cardiac output in the presence of
      adequate intravascular volume associated with an inadequate tissue perfusion
      including a physiological reduction in the splanchnic territory. It may occur in
      isolation as a reflection of cardiac pathology, or it may be part of a shock
      syndrome involving other pathogenic mechanisms. As the use of enteral nutrition
      (EN) is associated with an increase in mesenteric arterial output, EN could be
      deleterious by overwhelming the mechanisms of mesenteric adaptation. Accordingly,
      EN has been suspected to increase the risk of mesenteric ischaemia, bacterial
      translocation and sepsis in ICU patients with cardiogenic shock. International
      guidelines recommend a cautious use of EN within 72 h following cardiogenic
      shock. Recent evidence indicates that mesenteric arterial output may decrease
      during parenteral nutrition administration, suggesting that parenteral nutrition
      could have a protective effect on splanchnic organs in ICU patients with
      cardiogenic shock. Contrary to former beliefs, several meta-analyses have shown
      that parenteral nutrition is not associated with increased mortality. Exclusive
      EN is associated with negative energy balance and the combination of EN with
      supplemental parenteral nutrition during the first days following ICU admission
      has been proposed to prevent negative energy balance. Such a nutritional strategy
      could also be beneficial for the mesenteric circulation in cardiogenic shock, and
      consequently may improve the clinical outcome of patients with cardiogenic shock.
      Clinical trials are warranted to verify these hypotheses.

PMID- 21086114
TI  - Early life stress paradigms in rodents: potential animal models of depression?
AB  - RATIONALE: While human depressive illness is indeed uniquely human, many of its
      symptoms may be modeled in rodents. Based on human etiology, the assumption has
      been made that depression-like behavior in rats and mice can be modulated by some
      of the powerful early life programming effects that are known to occur after
      manipulations in the first weeks of life. OBJECTIVE: Here we review the evidence
      that is available in literature for early life manipulation as risk factors for
      the development of depression-like symptoms such as anhedonia, passive coping
      strategies, and neuroendocrine changes. Early life paradigms that were evaluated
      include early handling, separation, and deprivation protocols, as well as
      enriched and impoverished environments. We have also included a small number of
      stress-related pharmacological models. RESULTS: We find that for most early life
      paradigms per se, the actual validity for depression is limited. A number of
      models have not been tested with respect to classical depression-like behaviors,
      while in many cases, the outcome of such experiments is variable and depends on
      strain and additional factors. CONCLUSION: Because programming effects confer
      vulnerability rather than disease, a number of paradigms hold promise for
      usefulness in depression research, in combination with the proper genetic
      background and adult life challenges.

PMID- 21086115
TI  - JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the
      abuse-related effects of alcohol in rats.
AB  - RATIONALE: A few recent studies suggest that brain histamine levels and signaling
      via H(3) receptors play an important role in modulation of alcohol stimulation
      and reward in rodents. OBJECTIVE: The present study characterized the effects of
      a novel, selective, and brain penetrant H(3) receptor antagonist (JNJ-39220675)
      on the reinforcing effects of alcohol in rats. METHODS: The effect of JNJ
      39220675 on alcohol intake and alcohol relapse-like behavior was evaluated in
      selectively bred alcohol-preferring (P) rats using the standard two-bottle choice
      method. The compound was also tested on operant alcohol self administration in
      non-dependent rats and on alcohol-induced ataxia using the rotarod apparatus. In
      addition, alcohol-induced dopamine release in the nucleus accumbens was tested in
      freely moving rats. RESULTS: Subcutaneous administration of the selective H(3)
      receptor antagonist dose-dependently reduced both alcohol intake and preference
      in alcohol-preferring rats. JNJ-39220675 also reduced alcohol preference in the
      same strain of rats following a 3-day alcohol deprivation. The compound
      significantly and dose-dependently reduced alcohol self-administration without
      changing saccharin self-administration in alcohol non-dependent rats.
      Furthermore, the compound did not change the ataxic effects of alcohol, alcohol
      elimination rate, nor alcohol-induced dopamine release in nucleus accumbens.
      CONCLUSIONS: These results indicate that blockade of H(3) receptor should be
      considered as a new attractive mechanism for the treatment of alcoholism.

PMID- 21086116
TI  - Comparison of self-administration behavior and responsiveness to drug-paired cues
      in rats running an alley for intravenous heroin and cocaine.
AB  - RATIONALE: Evidence suggests that responsiveness to a drug-paired cue is
      predicted by the reinforcing magnitude of the drug during prior self
      administration. It remains unclear, however, if this principle holds true when
      comparisons are made across drug reinforcers. OBJECTIVE: The current study was
      therefore devised to test the hypothesis that differences in the animals'
      responsiveness to a cocaine- or heroin-paired cue presented during extinction
      would reflect differences in the patterns of prior cocaine and heroin runway self
      administration. METHODS: Rats ran a straight alley for single intravenous
      injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each
      paired with a distinct olfactory cue. Animals experienced 15 trials with each
      drug reinforcer in a counterbalanced manner. Start latencies, run times, and
      retreat behaviors (a form of approach-avoidance conflict) provided behavioral
      indices of the subjects' motivation to seek the reinforcer on each trial.
      Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of
      non-reinforced extinction trials. Other animals underwent conditioned place
      preference (CPP) testing to ensure that the two drug reinforcers were capable of
      producing drug-cue associations. RESULTS: While both drugs produced comparable
      CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced
      by faster start and run times and fewer retreats. In contrast, cocaine- but not
      heroin-paired cues produced increases in drug-seeking behavior during subsequent
      extinction trials. CONCLUSIONS: The subjects' responsiveness to drug-paired cues
      during extinction was not predicted by differences in the motivation to seek
      heroin versus cocaine during prior drug self-administration.

PMID- 21086117
TI  - Zolpidem and zopiclone impair similarly monotonous driving performance after a
      single nighttime intake in aged subjects.
AB  - RATIONALE: Although hypnotics are primarily used by older people, the residual
      effects the morning after a single nighttime intake of the two most commonly
      prescribed hypnotics, zolpidem (Zp) and zopiclone (Zc), on older middle-aged
      drivers have not been evaluated and compared. METHODS: Sixteen healthy subjects,
      55 to 65 years of age, participated in this double-blind, balanced, cross-over
      study. Zc (7.5 mg), Zp (10 mg) and flunitrazepam (Fln) (1 mg) or a placebo was
      administered at each subject's home at 11.00 pm. The next morning, at 9.00 am,
      the subjects had to drive in a simulated monotonous driving environment for 1 h.
      During each morning session, two blood samples were collected, and subjective
      feelings of alertness were completed three times. RESULTS: In comparison to
      placebo, Zp and Zc equivalently and significantly impaired the standard deviation
      of lateral position, the standard deviation of speed and the number of road
      exits. Detectable blood concentrations were found with Zp in 11 subjects at 8.30
      am and at 1.30 pm. The subjective alertness factor was significantly impaired
      with Zp. CONCLUSIONS: This is the first study revealing residual effects of Zp on
      driving performance in ageing drivers which are similar to that of Zc. Studying
      the effects of medication in different age ranges appears useful to complete the
      studies on behavioural-pharmacological effects of medication. To reduce the
      incidence of driving accidents due to prescription drugs, patients should be
      warned at the time of treatment initiation that they should avoid driving.

PMID- 21086118
TI  - Automatic recording of mediating behavior in delayed matching- and nonmatching-to
      position procedures in rats.
AB  - RATIONALE: Delayed matching-to-position and nonmatching-to-position procedures
      are widely used to model working memory in rodents. Mediating behavior-which
      enhances performance but is not explicitly required by the task-is generally
      considered an obstacle to the measurement of memory, but often occurs despite
      attempts to prevent it. The ubiquitous nature of mediating behavior suggests it
      might be analogous to rehearsal, an important component of learning and memory in
      humans. OBJECTIVES: The aim was to study an easily recordable, rehearsal-like
      mediating response in rats under baseline conditions and after treatment with
      amnestic drugs [scopolamine (0.1-0.3 mg/kg) and delta-9-tetrahydrocannabinol
      (THC; 1-5.6 mg/kg)]. METHODS: Lighted nosepoke holes were used to present
      position cues and record delayed matching or nonmatching responses. Performance
      of a distractor task was required to prevent simply waiting at the correct
      choice, but the nosepoke holes were left accessible during the delay. RESULTS:
      Each rat trained with the nonmatching task exhibited one of two mediating
      "strategies" that increased the odds of a correct choice: responding in the to-be
      correct hole during the delay or responding in the opposite hole during the
      delay. Rats trained with the matching task all showed the former strategy.
      Treatment with scopolamine disrupted performance of the mediating response.
      Scopolamine and THC both decreased the effectiveness of the mediating response,
      increasing errors even on trials when the "appropriate" mediating behavior did
      occur. CONCLUSIONS: The procedures and data analysis approach used here provide
      an objective, automated means of measuring mediating behavior, which might be
      useful as an animal model of memory rehearsal.

PMID- 21086119
TI  - A computer-automated touchscreen paired-associates learning (PAL) task for mice:
      impairments following administration of scopolamine or dicyclomine and
      improvements following donepezil.
AB  - RATIONALE: Performance on the Cambridge Neuropsychological Test Automated Battery
      touchscreen paired-associates learning (PAL) test is predictive of Alzheimer's
      disease and impaired in schizophrenia and chronic drug users. An automated
      computer touchscreen PAL task for rats has been previously established. A
      pharmacologically validated PAL task for mice would be a highly valuable tool,
      which could be useful for a number of experimental aims including drug discovery.
      OBJECTIVES: This study sought to investigate the effects of systemic
      administration of cholinergic agents on task performance in C57Bl/6 mice.
      METHODS: Scopolamine hydrobromide (0.02, 0.2, and 2.0 mg/kg), dicyclomine
      hydrochloride (M(1) receptor antagonist; 2.0, 4.0, and 8.0 mg/kg), and donepezil
      hydrochloride (cholinesterase inhibitor; 0.03, 0.1, and 0.3 mg/kg) were
      administered post-acquisition in C57Bl/6 mice performing the PAL task. RESULTS:
      Scopolamine (0.2 and 2.0 mg/kg) and dicyclomine (at all administered doses)
      significantly impaired PAL performance. A significant facilitation in PAL was
      revealed in mice following donepezil administration (0.3 mg/kg). CONCLUSIONS: The
      present study shows that mice can acquire the rodent PAL task and that the
      cholinergic system is important for PAL task performance. M(1) receptors in
      particular are likely implicated in normal performance of PAL. The finding that
      mouse PAL can detect both impairments and improvements indicates that this task
      could prove to be a highly valuable tool for a number of experimental aims
      including drug discovery.

PMID- 21086120
TI  - Selective pressure to increase charge in immunodominant epitopes of the H3
      hemagglutinin influenza protein.
AB  - The evolutionary speed and the consequent immune escape of H3N2 influenza A virus
      make it an interesting evolutionary system. Charged amino acid residues are often
      significant contributors to the free energy of binding for protein-protein
      interactions, including antibody-antigen binding and ligand-receptor binding. We
      used Markov chain theory and maximum likelihood estimation to model the evolution
      of the number of charged amino acids on the dominant epitope in the hemagglutinin
      protein of circulating H3N2 virus strains. The number of charged amino acids
      increased in the dominant epitope B of the H3N2 virus since introduction in
      humans in 1968. When epitope A became dominant in 1989, the number of charged
      amino acids increased in epitope A and decreased in epitope B. Interestingly, the
      number of charged residues in the dominant epitope of the dominant circulating
      strain is never fewer than that in the vaccine strain. We propose these results
      indicate selective pressure for charged amino acids that increase the affinity of
      the virus epitope for water and decrease the affinity for host antibodies. The
      standard PAM model of generic protein evolution is unable to capture these
      trends. The reduced alphabet Markov model (RAMM) model we introduce captures the
      increased selective pressure for charged amino acids in the dominant epitope of
      hemagglutinin of H3N2 influenza (R (2) > 0.98 between 1968 and 1988). The RAMM
      model calibrated to historical H3N2 influenza virus evolution in humans fit well
      to the H3N2/Wyoming virus evolution data from Guinea pig animal model studies.

PMID- 21086121
TI  - Frequent loss of heterozygosity in the beta2-microglobulin region of chromosome
      15 in primary human tumors.
AB  - Downregulation or total loss of HLA class I expression on tumor cells is known as
      a mechanism of cancer immune escape. Alterations of the HLA phenotype are
      frequently due to mutations affecting genes encoding the HLA class I heavy chains
      located on chromosome 6p21 or the beta2-microglobulin (beta2m) gene encoding the
      light chain of the HLA complex located on chromosome 15q21. Frequently
      irreversible total loss of HLA class I molecules is due to the coincidence of two
      molecular events, the mutation of one beta2m gene and the loss of the second
      copy. The latter is detectable as loss of heterozygosity (LOH) of microsatellite
      markers in the beta2m region on chromosome 15q21 (LOH-15q21). Thus, LOH-15q21
      might be an important event in the processes of HLA class I downregulation and
      total loss. Here we studied the frequency of LOH-15q21 in tumor tissues of
      different entities. By determining the status of heterozygosity of two
      microsatellite markers we detected LOH-15q21 in 44% of bladder carcinomas (n =
      69), in 35% of colon carcinomas (n = 95), in 16% of melanomas (n = 70) but only
      in 7% of renal cancers (n = 45). Moreover, we observed a frequent coincidence of
      LOH-15q21 and LOH-6p21 in colorectal carcinoma, bladder carcinoma and melanoma,
      but not for renal carcinoma. We believe that the high incidence of LOH-15q21 in
      some malignancies and especially the coincidence of LOH-15q21 and LOH-6p21 might
      have a strong impact on tumor immunogenicity and on the efficiency of cancer
      immunotherapy.

PMID- 21086122
TI  - Impact of MHC class II polymorphism on blood counts of CD4+ T lymphocytes in
      macaque.
AB  - While the number of peripheral blood T lymphocytes and of their two main subsets
      (CD4+CD8- and CD4-CD8+) varies little in a given healthy individual, substantial
      variation is observed between individuals. It was proposed that these counts
      could be influenced by MHC polymorphisms because of the well-established role of
      MHC molecules in thymic T lymphocyte maturation and presentation of antigenic
      peptides to peripheral T lymphocytes. To test this hypothesis, we have chosen the
      crab-eating macaque (Macaca fascicularis), an animal model phylogenetically close
      to man. We selected the Philippine macaque population because of a restriction of
      the MHC polymorphism in this islander population. Peripheral blood lymphocytes
      were counted with an automated analyzer and T lymphocyte subsets were assessed by
      immunolabeling and flow cytometry. The MHC polymorphism was investigated in 200
      unrelated subjects using 14 microsatellites markers distributed across the MHC
      and the DRB locus that was genotyped by denaturing gradient gel electrophoresis
      and sequencing. All markers were in Hardy-Weinberg equilibrium. Allelic
      associations were tested with the UNPHASED software. We revealed a significant
      influence of the MHC class II region on CD4+ T lymphocyte blood count with the
      largest effect associated with a two-locus haplotypes combining the DRACA allele
      274 and the DRB haplotype #8a (p < 8 * 10(-7)). Our data should stimulate a
      similar association study of the CD4+ T cell counts in humans.

PMID- 21086123
TI  - A possible association of EMID2 polymorphisms with aspirin hypersensitivity in
      asthma.
AB  - Aspirin-intolerant asthma (AIA) is an asthma phenotype characterized by the
      development of bronchoconstriction following ingestion of aspirin. Despite the
      well-defined pathological trigger, the underlying mechanisms of AIA are still
      unclear. With the biophysical characteristics of the human EMI domain-containing
      protein 2 (EMID2) gene in relation to the extracellular matrix deposition and
      epithelial-mesenchymal transition as pivotal characteristics of airway remodeling
      in asthma, we hypothesized that genetic polymorphisms of EMID2 might affect the
      development of AIA. In this study, the allelic associations of 49 single
      nucleotide polymorphisms (SNPs) of the human EMID2 gene were evaluated from 163
      AIA patients and 429 aspirin-tolerant asthma (ATA) subjects as controls in a
      Korean population. Logistic analysis showed that five SNPs (P = 0.01-0.04, but P
      (corr) > 0.05) and EMID2_BL2_ht2 haplotype (unique to the minor alleles of
      rs4727494 and rs13233066; P = 0.02; P (corr) = 0.02) were significantly
      associated with AIA. More interestingly, regression analysis of the decline of
      forced expiratory volume in one second (FEV(1)) by aspirin provocation revealed
      that 10 SNPs (P = 0.003-0.04) and four relevant haplotypes (P = 0.002-0.02) were
      significantly associated with the fall rate of FEV(1) by aspirin provocation,
      indicating that genetic polymorphisms of EMID2 could cause meaningful deficits in
      the upper and lower airways among AIA patients. These findings provide evidence
      that EMID2 may be a susceptible genetic factor for aspirin hypersensitivity among
      asthmatics in Korean population.

PMID- 21086124
TI  - In vivo activity of novel anti-ErbB2 antibody chA21 alone and with Paclitaxel or
      Trastuzumab in breast and ovarian cancer xenograft models.
AB  - It was well studied that ErbB2 (HER2/p185(her2/neu)) overexpression in human
      malignant cancers correlates with poor prognosis and chemo-resistance. Although
      Trastuzumab (Herceptin) has been widely used in patients with ErbB2
      overexpressing metastatic breast cancer, many patients either do not respond to
      Trastuzumab therapy or progress within 1 year of initiating Trastuzumab
      treatment. Previously, we reported a novel tumor-inhibitory antibody chA21, which
      recognized ErbB2 extracellular domain with an epitope distinct from other tumor
      inhibitory anti-ErbB2 antibodies. Here, we report that chA21 combined with
      Paclitaxel or Trastuzumab significantly enhances the tumor-inhibition effects on
      ErbB2-overexpressing breast and ovarian cancer in xenograft mice. Moreover, the
      study reveals that the effects by chA21 to cause an enhanced inhibition on cancer
      cell proliferation and angiogenesis was highly associated with the intrinsic
      ability of chA21 to down-regulate ErbB2 receptor, inhibit downstream MAPK and
      PI3K-AKT signal transduction and activate natural killer cells. Our findings show
      that chA21 may represent a unique anti-ErbB2 antibody with potentials as
      therapeutic candidate alone or combination with other anti-ErbB2 reagents in
      cancer therapy.

PMID- 21086125
TI  - Effects of virtual reality simulator training method and observational learning
      on surgical performance.
AB  - BACKGROUND: Virtual reality (VR) simulators and Web-based instructional videos
      are valuable supplemental training resources in surgical programs, but it is
      unclear how to optimally integrate them into minimally invasive surgical
      training. METHODS: Medical students were randomized to proficiency-based training
      on VR laparoscopy and endoscopy simulators by two different methods: proctored
      training (automated simulator feedback plus human expert feedback) or independent
      training (simulator feedback alone). After achieving simulator proficiency,
      trainees performed a series of laparoscopic and endoscopic tasks in a live
      porcine model. Prior to their entry into the animal lab, all trainees watched an
      instructional video of the procedure and were randomly assigned to either observe
      or not observe the actual procedure before performing it themselves. The joint
      effects of VR training method and procedure observation on time to successful
      task completion were evaluated with Cox regression models. RESULTS: Thirty-two
      students (16 proctored, 16 independent) completed VR training. Cox regression
      modeling with adjustment for relevant covariates demonstrated no significant
      difference in the likelihood of successful task completion for independent versus
      proctored training [Hazard Ratio (HR) 1.28; 95% Confidence Interval (CI) 0.96
      1.72; p=0.09]. Trainees who observed the actual procedure were more likely to be
      successful than those who watched the instructional video alone (HR 1.47; 95% CI
      1.09-1.98; p=0.01). CONCLUSIONS: Proctored VR training is no more effective than
      independent training with respect to surgical performance. Therefore, time
      consuming human expert feedback during VR training may be unnecessary.
      Instructional videos, while useful, may not be adequate substitutes for actual
      observation when trainees are learning minimally invasive surgical procedures.

PMID- 21086126
TI  - Re: Routine ultrasound and limited computed tomography for the diagnosis acute
      appendicitis. Editor's note.

PMID- 21086128
TI  - In vivo studies of Clostridium perfringens in mouse gas gangrene model.
AB  - Understanding the pathogenesis of infectious diseases requires comprehensive
      knowledge of the proteins expressed by the pathogen during in vivo growth in the
      host. Proteomics provides the tools for such analyses but the protocols required
      to purify sufficient quantities of the pathogen from the host organism are
      currently lacking. In this study, we have separated Clostridium perfringens, a
      highly virulent bacterium and potential BTW agent, from the peritoneal fluid of
      infected mice using Percoll density gradient centrifugation. The bacterium could
      be isolated in quantities sufficient to carry out meaningful proteomic
      comparisons with in vitro grown bacteria. Furthermore, the isolates were found to
      be virtually free from contaminating host proteins. Microscopy revealed major
      morphological changes under host conditions at different stages of infection.
      Profile of immunogenic proteins from in vivo- and TPYG-grown whole cell lysate
      using mouse anti-gangrene serum indicated over-expression of several proteins
      especially in the low molecular weight region. Expression of two virulence
      determinants, ornithine carbamoyl transferase (cOTC), and cystathionine beta
      lyase (CBL), under in vivo conditions has also been studied. Two-dimensional gel
      analysis revealed a host induced proteome which was apparently different in
      comparison to in vitro grown cells. Detailed proteomic elucidation of
      differentially expressed proteins shown here is likely to provide valuable
      insight towards understanding the complexity of the adaptive response of C.
      perfringens to the host environment.

PMID- 21086129
TI  - Evaluation of genetic manipulation strategies on D-lactate production by
      Escherichia coli.
AB  - In order to rationally manipulate the cellular metabolism of Escherichia coli for
      D: -lactate production, single-gene and multiple-gene deletions with mutations in
      acetate kinase (ackA), phosphotransacetylase (pta), phosphoenolpyruvate synthase
      (pps), pyruvate formate lyase (pflB), FAD-binding D-lactate dehydrogenase (dld),
      pyruvate oxidase (poxB), alcohol dehydrogenase (adhE), and fumarate reductase
      (frdA) were tested for their effects in two-phase fermentations (aerobic growth
      and oxygen-limited production). Lactate yield and productivity could be improved
      by single-gene deletions of ackA, pta, pflB, dld, poxB, and frdA in the wild type
      E. coli strain but were unfavorably affected by deletions of pps and adhE.
      However, fermentation experiments with multiple-gene mutant strains showed that
      deletion of pps in addition to ackA-pta deletions had no effect on lactate
      production, whereas the additional deletion of adhE in E. coli B0013-050 (ackA
      pta pps pflB dld poxB) increased lactate yield. Deletion of all eight genes in E.
      coli B0013 to produce B0013-070 (ackA-pta pps pflB dld poxB adhE frdA) increased
      lactate yield and productivity by twofold and reduced yields of acetate,
      succinate, formate, and ethanol by 95, 89, 100, and 93%, respectively. When
      tested in a bioreactor, E. coli B0013-070 produced 125 g/l D-lactate with an
      increased oxygen-limited lactate productivity of 0.61 g/g h (2.1-fold greater
      than E. coli B0013). These kinetic properties of D-lactate production are among
      the highest reported and the results have revealed which genetic manipulations
      improved D-lactate production by E. coli.

PMID- 21086130
TI  - Candida galli strain PGO6: a novel isolated yeast strain capable of
      transformation of isoeugenol into vanillin and vanillic acid.
AB  - Candida galli strain PGO6 isolated from oil-contaminated water is the first
      isolated yeast strain which is capable to form vanillin and vanillic acid during
      isoeugenol biotransformation. The products were confirmed by thin-layer
      chromatography (TLC), changes in the UV absorption pattern and high-performance
      liquid chromatography (HPLC). The phenotypic and physiochemical characteristics
      as well as molecular phylogenetic analysis based on amplification the ITS1-5.8S
      ITS2 rDNA regions indicated the isolated strain PGO6 was identified as C. galli
      (GenBank accession number HM641231). Resting cells of C. galli PGO6 from the late
      exponential of growth phase were used as biocatalysts for the biotransformation
      of isoeugenol. The optimal molar conversion of vanillin (48%) and vanillic acid
      (19%) was obtained after a 30 h incubation using 0.1% (v/v) of isoeugenol and 6
      mg of dry weight of cells per ml without further optimization. Under these
      conditions, the total amount of vanillin and vanillic acid was 583 mg l(-1).
      Further biotransformation was carried out using 0.5% (v/v) of isoeugenol under
      the resting cells conditions, yielding a vanillin concentration of 1.12 g l(-1)
      (molar yield 25.7%) after 60 h incubation. This study brings the first evidence
      for biotransformation of isoeugenol to vanillin and vanillic acid by a yeast
      strain.

PMID- 21086131
TI  - Cross-species induction of antimicrobial compounds, biosurfactants and quorum
      sensing inhibitors in tropical marine epibiotic bacteria by pathogens and
      biofouling microorganisms.
AB  - Enhancement or induction of antimicrobial, biosurfactant, and quorum-sensing
      inhibition property in marine bacteria due to cross-species and cross-genera
      interactions was investigated. Four marine epibiotic bacteria (Bacillus sp. S3,
      B. pumilus S8, B. licheniformis D1, and Serratia marcescens V1) displaying
      antimicrobial activity against pathogenic or biofouling fungi (Candida albicans
      CA and Yarrowia lipolytica YL), and bacteria (Pseudomonas aeruginosa PA and
      Bacillus pumilus BP) were chosen for this study. The marine epibiotic bacteria
      when co-cultivated with the aforementioned fungi or bacteria showed induction or
      enhancement in antimicrobial activity, biosurfactant production, and quorum
      sensing inhibition. Antifungal activity against Y. lipolytica YL was induced by
      co-cultivation of the pathogens or biofouling strains with the marine Bacillus
      sp. S3, B. pumilus S8, or B. licheniformis D1. Antibacterial activity against Ps.
      aeruginosa PA or B. pumilus BP was enhanced in most of the marine isolates after
      co-cultivation. Biosurfactant activity was significantly increased when cells of
      B. pumilus BP were co-cultivated with S. marcescens V1, B. pumilus S8, or B.
      licheniformis D1. Pigment reduction in the quorum-sensing inhibition indicator
      strain Chromobacterium violaceum 12472 was evident when the marine strain of
      Bacillus sp. S3 was grown in the presence of the inducer strain Ps. aeruginosa
      PA, suggesting quorum-sensing inhibition. The study has important ecological and
      biotechnological implications in terms of microbial competition in natural
      environments and enhancement of secondary metabolite production.

PMID- 21086132
TI  - Hemprich's long-eared bat (Otonycteris hemprichii) as a predator of scorpions:
      whispering echolocation, passive gleaning and prey selection.
AB  - Over 70% of the droppings of the gleaning bat Otonycteris hemprichii can contain
      scorpion fragments. Yet, some scorpions found in its desert habitat possess venom
      of the highest known toxicity, rendering them a very dangerous prey. In this
      study, we describe how O. hemprichii catches and handles scorpions, quantify its
      flight and echolocation behaviour in the field, investigate what sensory modality
      it uses to detect scorpions, and test whether it selects scorpions according to
      their size or toxicity. We confirmed that O. hemprichi is a whispering bat
      (approx. 80 dB peSPL) with short, multi-harmonic calls. In a flight room we also
      confirmed that O. hemprichii detects scorpions by their walking noises.
      Amplitudes of such noises were measured and they reach the flying bat at or below
      the level of echoes of the loess substrate. Bats dropped straight onto moving
      scorpions and were stung frequently even straight in their face. Stings did not
      change the bats' behaviour and caused no signs of poisoning. Scorpions were eaten
      including poison gland and stinger. Bats showed no preference neither for any of
      the scorpion species nor their size suggesting they are generalist predators with
      regard to scorpions.

PMID- 21086133
TI  - Absence of chromosome 19q13.41 amplification in a case of atypical
      teratoid/rhabdoid tumor with ependymoblastic differentiation.

PMID- 21086134
TI  - Early-onset bipolar disorder: how about visual-spatial skills and executive
      functions?
AB  - Early-onset bipolar disorder is an impairing condition that is strongly
      associated with genetic inheritance. Neurocognitive deficits are core traits of
      this disorder which seem to be present in both young and adult forms. Deficits in
      verbal memory and attention are persistent within euthymic phases in bipolar
      adults, adolescents, and children. In younger samples, including type I or II and
      not otherwise specified patients, executive functions are not widely impaired and
      the existence of visual-spatial deficits remains unclear. The main aim of this
      study was to compare the neurocognitive performance in young stabilized type I or
      II bipolar patients and healthy controls. Fifteen medicated adolescents with
      bipolar disorder and 15 healthy adolescents, matched in age and gender, were
      compared on visual-spatial skills (reasoning, memory, visual-motor accuracy) and
      executive functioning (attention and working memory, set-shifting, inhibition)
      using t-tests and MANCOVA. Correcting for verbal competence, MANCOVA showed that
      patients performed significantly worse than controls in letters and numbers
      sequencing (P = 0.003), copy (P < 0.001) and immediate recall (P = 0.007) of the
      Rey Complex Figure Test, interference of the Stroop Color-Word Test (P = 0.007)
      and non-perseverative errors on the Wisconsin Card Sorting Test (P = 0.038).
      Impaired cognitive performance was found in young bipolar patients in working
      memory, visual-motor skills, and inhibitory control.

PMID- 21086135
TI  - Akt and PKC are involved not only in upregulation of telomerase activity but also
      in cell differentiation-related function via mTORC2 in leukemia cells.
AB  - We have shown previously that PI3K/Akt pathway is active after cell
      differentiation in HL60 cells. In the present study, we have investigated whether
      additional molecules, such as protein kinase C (PKC), are involved in the
      regulation, not only of telomerase, but also of leukemia cell differentiation. We
      show that PKC activates telomerase and is, itself, activated following VD3- or
      ATRA-induced differentiation of HL60 cells, as was observed for PI3K/Akt. To
      clarify the significance of PI3K/Akt and PKC pathway activation in leukemia cell
      differentiation, we examined the active proteins in either the downstream or
      upstream regulation of these pathways. In conjunction with the activation of Akt
      or PKC, mTOR and S6K were phosphorylated and the protein expression levels of
      Rictor were increased, compared with Raptor, following cell differentiation.
      Silencing by Rictor siRNA resulted in the attenuation of Akt phosphorylation on
      Ser473 and PKCalpha/betaII phosphorylation, as well as the inhibition of Rictor
      itself, suggesting that Rictor is an upstream regulator of both Akt and PKC. In
      addition, in cells induced to differentiate by ATRA or VD3, Nitroblue-tetrazolium
      (NBT) reduction and esterase activity, were blocked either by LY294002, a PI3K
      inhibitor, or by BIM, a PKC inhibitor, without affecting cell surface markers
      such as CD11b or CD14. Intriguingly, the silencing of Rictor by its siRNA also
      suppressed the reducing ability of NBT following VD3-induced cell
      differentiation. Taken together, our results show that Rictor associated with
      mTOR (mTORC2) regulates the activity of both Akt and PKC that are involved in
      cell functions such as NBT reduction and esterase activity induced by leukemia
      cell differentiation.

PMID- 21086137
TI  - In situ hybridization reveals that type I and III collagens are produced by
      pericytes in the anterior pituitary gland of rats.
AB  - Type I and III collagens widely occur in the rat anterior pituitary gland and are
      the main components of the extracellular matrix (ECM). Although ECM components
      possibly play an important role in the function of the anterior pituitary gland,
      little is known about collagen-producing cells. Type I collagen is a heterotrimer
      of two alpha1(I) chains (the product of the col1a1 gene) and one alpha2(I) chain
      (the product of the col1a2 gene). Type III collagen is a homotrimer of
      alpha1(III) chains (the product of the col3a1 gene). We used in situ
      hybridization with digoxigenin-labeled cRNA probes to examine the expression of
      col1a1, col1a2, and col3a1 mRNAs in the pituitary gland of adult rats. mRNA
      expression for these collagen genes was clearly observed, and cells expressing
      col1a1, col1a2, and col3a1 mRNA were located around capillaries in the gland. We
      also investigated the possible double-staining of collagen mRNA and pituitary
      hormones, S-100 protein (a marker of folliculo-stellate cells), or desmin (a
      marker of pericytes). Col1a1 and col3a1 mRNA were identified in desmin
      immunopositive cells. Thus, only pericytes produce type I and III collagens in
      the rat anterior pituitary gland.

PMID- 21086136
TI  - Rapid evolution of a novel signalling mechanism by concerted duplication and
      divergence of a BMP ligand and its extracellular modulators.
AB  - Gene duplication and divergence is widely considered to be a fundamental
      mechanism for generating evolutionary novelties. The Bone Morphogenetic Proteins
      (BMPs) are a diverse family of signalling molecules found in all metazoan genomes
      that have evolved by duplication and divergence from a small number of ancestral
      types. In the fruit fly Drosophila, there are three BMPs: Decapentaplegic (Dpp)
      and Glass bottom boat (Gbb), which are the orthologues of vertebrate BMP2/4 and
      BMP5/6/7/8, respectively, and Screw (Scw), which, at the sequence level, is
      equally divergent from Dpp and Gbb. It has recently been shown that Scw has
      arisen from a duplication of Gbb in the lineage leading to higher Diptera. We
      show that since this duplication event, Gbb has maintained the ancestral
      BMP5/6/7/8 functionality while Scw has rapidly diverged. The evolution of Scw was
      accompanied by duplication and divergence of a suite of extracellular regulators
      that continue to diverge together in the higher Diptera. In addition, Scw has
      become restricted in its receptor specificity: Gbb proteins can signal through
      the Type I receptors Thick veins (Tkv) and Saxophone (Sax), while Scw signals
      through Sax. Thus, in a relatively short span of evolutionary time, the
      duplication event that gave rise to Scw produced not only a novel ligand but also
      a novel signalling mode that is functionally distinct from the ancestral Gbb
      mode. Our results demonstrate the plasticity of the BMP pathway not only in
      evolving new family members and new functions but also new signalling modes by
      redeploying key regulators in the pathway.

PMID- 21086138
TI  - Cloning and expression of a novel component of the CAP superfamily enhanced in
      the inflammatory response to LPS of the ascidian Ciona intestinalis.
AB  - The CAP superfamily is a group of proteins that have been linked to several
      biological functions such as reproduction, cancer, and immune defense. A
      differential screening between lipopolysaccharide (LPS)-challenged and naive
      Ciona intestinalis has been performed to identify LPS-induced genes. This
      strategy has allowed the isolation of a full-length 1471-bp cDNA encoding for a
      413-amino-acid protein (CiCAP). In silico analysis has shown that this
      polypeptide displays a modular structure with similarities to vertebrate CAP
      superfamily proteins and to a collagen-binding adhesin of Streptococcus mutans.
      Domain organization analysis and alignment of CiCAP to other vertebrate CAP
      proteins have revealed a novel structure suggesting that this protein originated
      from a common ancestor gene that gave rise to many subfamilies of mosaic proteins
      with novel functions. Quantitative mRNA expression performed by real-time
      polymerase chain reaction analysis has demonstrated that this gene is rapidly
      activated in the pharynx of C. intestinalis a few hours after LPS injection.
      Moreover, in situ hybridization has shown that CiCAP mRNA is highly expressed by
      hemocytes with large granules contained inside the pharynx vessels. Thus, CiCAP
      represents a protein with novel structural domains involved in ascidian immune
      responses.

PMID- 21086139
TI  - In vitro characterization of proliferation and differentiation of trout satellite
      cells.
AB  - Fish satellite cells have been extracted from various species, but the myogenic
      characteristics of these cells in culture remain largely unknown. We show here
      that 60%-70% of the adherent cells are myogenic based on their immunoreactivity
      for the myogenic regulatory factor MyoD. In DMEM containing 10% fetal calf serum
      (FCS), trout myoblasts display rapid expression of myogenin (18% of myogenin
      positive cells at day 2) combined with rapid fusion into myotubes (50% of
      myogenin-positive nuclei and 30% nuclei in myosin heavy chain [MyHC]-positive
      cells at day 7). These kinetics of differentiation are reminiscent of the
      behavior of fetal myoblasts in mammals. However, not all the myogenic cells
      differentiate; this subpopulation of cells might correspond to the previously
      named "reserve" cells. More than 90% of the BrdU-positive cells are also positive
      for MyoD, indicating that myogenic cells proliferate in vitro. By contrast, less
      than 1% of myogenin-positive cells are positive for BrdU suggesting that myogenin
      expression occurs only in post-mitotic cells. In order to maximize either the
      proliferation or the differentiation of cells, we have defined new culture
      conditions based on the use of a proliferation medium (F10+10%FCS) and a
      differentiation medium (DMEM+2%FCS). Three days after switching the medium, the
      differentiation index (% MyHC-positive nuclei) is 40-fold higher than that in
      proliferation medium, whereas the proliferation index (% BrdU-positive nuclei) is
      three-fold lower. Stimulation of cell proliferation by insulin-like growth factor
      1 (IGF1), IGF2, and FGF2 is greater in F10 medium. The characterization of these
      extracted muscle cells thus validates the use of this in vitro system of
      myogenesis in further studies of the myogenic activity of growth factors in
      trout.

PMID- 21086140
TI  - Remodeling of the notochord during development of vertebral fusions in Atlantic
      salmon (Salmo salar).
AB  - Histological characterization of spinal fusions in Atlantic salmon (Salmo salar)
      has demonstrated shape alterations of vertebral body endplates, a reduced
      intervertebral space, and replacement of intervertebral cells by ectopic bone.
      However, the significance of the notochord during the fusion process has not been
      addressed. We have therefore investigated structural and cellular events in the
      notochord during the development of vertebral fusions. In order to induce
      vertebral fusions, Atlantic salmon were exposed to elevated temperatures from
      fertilization until they attained a size of 15g. Based on results from
      radiography, intermediate and terminal stages of the fusion process were
      investigated by immunohistochemistry and real-time quantitative polymerase chain
      reaction. Examination of structural extracellular matrix proteins such as
      Perlecan, Aggrecan, Elastin, and Laminin revealed reduced activity and
      reorganization at early stages in the pathology. Staining for elastic fibers
      visualized a thinner elastic membrane surrounding the notochord of developing
      fusions, and immunohistochemistry for Perlecan showed that the notochordal sheath
      was stretched during fusion. These findings in the outer notochord correlated
      with the loss of Aggrecan- and Substance-P-positive signals and the further loss
      of vacuoles from the chordocytes in the central notochord. At more progressed
      stages of fusion, chordocytes condensed, and the expression of Aggrecan and
      Substance P reappeared. The hyperdense regions seem to be of importance for the
      formation of notochordal tissue into bone. Thus, the remodeling of notochord
      integrity by reduced elasticity, structural alterations, and cellular changes is
      probably involved in the development of vertebral fusions.

PMID- 21086141
TI  - Perception of healthcare providers versus patient reported incidence of
      chemotherapy-induced nausea and vomiting after the addition of NK-1 receptor
      antagonists.
AB  - PURPOSE: Physicians and nurses often underestimate the incidence of chemotherapy
      induced nausea and vomiting (CINV) after both highly emetogenic chemotherapy
      (HEC) and moderately emetogenic chemotherapy (MEC). This study assesses
      physicians' and nurses' perceptions of CINV in their own practices after the
      introduction of aprepitant. METHODS: A prospective observational study of
      patients receiving the first cycle of HEC regimens with CDDP and without CDDP or
      MEC was performed. Eligible patients completed a 6-day diary recording emetic
      episodes, nausea assessment, and antiemetic medication use. Physicians and nurses
      estimated the incidence of acute and delayed CINV after the first administration
      of HEC and MEC. The observed incidence rates of CINV were compared with the rates
      predicted by healthcare providers. Aprepitant was given to patients receiving HEC
      regimes with CDDP. RESULTS: Twenty-nine physicians and nurses and 95 patients
      (87% receiving HEC and 14% MEC) were recruited. The global control of CINV was
      66.67% for all patients and 73.33%, 47.06%, and 55.56% for patients receiving HEC
      regimens with CDDP, HEC regimens without CDDP and MEC, respectively. Physicians
      and nurses underestimated the control of acute CINV in patients receiving HEC
      regimens with CDDP, but they accurately predicted the control of delayed CINV.
      All physicians and nurses predicted the control of acute CINV after HEC regiments
      without CDDP and after MEC quite accurately, whereas they overestimated the
      control of delayed CINV after both regimens. CONCLUSIONS: Aprepitant allows for
      better control of CINV in HEC regimens with CDDP, and this control is accurately
      perceived by physicians and nurses. However, physicians and nurses overestimate
      the control of delayed CINV after HEC regimens without CDDP and after MEC. CINV
      is still an important target for improved therapeutic intervention and the
      healthcare providers must be aware of its actual incidence.

PMID- 21086145
TI  - Pyoderma gangrenosum after inguinal hernia repair.
AB  - Pyoderma gangrenosum (PG) is an uncommon, ulcerative skin disease that is often
      associated with systemic illness. In rare cases, PG occurs after surgery, which
      can lead to delayed diagnosis as other causes such as wound breakdown or
      bacterial/fungal infection are considered. We report a rare case of PG following
      the repair of an inguinal hernia, and review the presentation of this disease
      after surgery.

PMID- 21086146
TI  - Clinical presentation and treatment of distal posterior inferior cerebellar
      artery aneurysms.
AB  - Aneurysms located at the distal portion of the posterior inferior cerebellar
      artery (PICA) are rare, and their clinical features are not fully understood. We
      report the clinical features and management of 30 distal PICA aneurysms in 28
      patients treated during the past decade at Kagoshima University Hospital and
      affiliated hospitals. Our series includes 20 women and eight men. Of their 30
      aneurysms, 24 were ruptured, and six were unruptured; there were 27 saccular and
      two fusiform aneurysms; one was dissecting. Their location was at the anterior
      medullary (n = 4), lateral-medullary (n = 9), tonsillomedullary (n = 7),
      telovelotonsillar (n = 6), and cortical (n = 4) segment of the PICA. In 18
      patients, angiographic features suggested hemodynamic stress including an absent
      contralateral PICA or ipsilateral anterior inferior cerebellar artery,
      termination of the vertebral artery (VA) at the PICA, and hyperplasia or
      occlusion of the contralateral VA. As three patients died before surgery, 27
      aneurysms in 25 patients were surgically treated. Of these, 6 were unruptured
      aneurysms; 20 were clipped via midline or lateral suboccipital craniotomy, and 5
      were embolized with Guglielmi coils; in one, the PICA flow was reconstructed by
      OA-PICA anastomosis, and in the other one, the PICA was resected. Of the 25
      surgically treated patients, 22 (88%) had good outcomes. The predominant
      contributor to the development of distal PICA aneurysms is thought to be
      increased hemodynamic stress attributable to anomalies in the PICA and related
      posterior circulation. Both direct clipping and coil embolization yielded
      favorable outcomes in our series. However, considering the difficulties that may
      be encountered at direct clipping in the acute stage and the availability of
      advanced techniques and instrumentation, aneurysmal coiling is now the first
      option to address these aneurysms.

PMID- 21086147
TI  - Combination of spectral and binaurally created harmonics in a common central
      pitch processor.
AB  - A fundamental attribute of human hearing is the ability to extract a residue
      pitch from harmonic complex sounds such as those produced by musical instruments
      and the human voice. However, the neural mechanisms that underlie this processing
      are unclear, as are the locations of these mechanisms in the auditory pathway.
      The ability to extract a residue pitch corresponding to the fundamental frequency
      from individual harmonics, even when the fundamental component is absent, has
      been demonstrated separately for conventional pitches and for Huggins pitch (HP),
      a stimulus without monaural pitch information. HP is created by presenting the
      same wideband noise to both ears, except for a narrowband frequency region where
      the noise is decorrelated across the two ears. The present study investigated
      whether residue pitch can be derived by combining a component derived solely from
      binaural interaction (HP) with a spectral component for which no binaural
      processing is required. Fifteen listeners indicated which of two sequentially
      presented sounds was higher in pitch. Each sound consisted of two "harmonics,"
      which independently could be either a spectral or a HP component. Component
      frequencies were chosen such that the relative pitch judgement revealed whether a
      residue pitch was heard or not. The results showed that listeners were equally
      likely to perceive a residue pitch when one component was dichotic and the other
      was spectral as when the components were both spectral or both dichotic. This
      suggests that there exists a single mechanism for the derivation of residue pitch
      from binaurally created components and from spectral components, and that this
      mechanism operates at or after the level of the dorsal nucleus of the lateral
      lemniscus (brainstem) or the inferior colliculus (midbrain), which receive inputs
      from the medial superior olive where temporal information from the two ears is
      first combined.

PMID- 21086148
TI  - Calcium-induced cleavage of DNA topoisomerase I involves the cytoplasmic-nuclear
      shuttling of calpain 2.
AB  - Important to the function of calpains is temporal and spatial regulation of their
      proteolytic activity. Here, we demonstrate that cytoplasm-resident calpain 2
      cleaves human nuclear topoisomerase I (hTOP1) via Ca(2+)-activated proteolysis
      and nucleoplasmic shuttling of proteases. This proteolysis of hTOP1 was induced
      by either ionomycin-caused Ca(2+) influx or addition of Ca(2+) in cellular
      extracts. Ca(2+) failed to induce hTOP1 proteolysis in calpain 2-knockdown cells.
      Moreover, calpain 2 cleaved hTOP1 in vitro. Furthermore, calpain 2 entered the
      nucleus upon Ca(2+) influx, and calpastatin interfered with this process. Calpain
      2 cleavage sites were mapped at K(158) and K(183) of hTOP1. Calpain 2-truncated
      hTOP1 exhibited greater relaxation activity but remained able to interact with
      nucleolin and to form cleavable complexes. Interestingly, calpain 2 appears to be
      involved in ionomycin-induced protection from camptothecin-induced cytotoxicity.
      Thus, our data suggest that nucleocytoplasmic shuttling may serve as a novel type
      of regulation for calpain 2-mediated nuclear proteolysis.

PMID- 21086149
TI  - Dictyostelium dynamin B modulates cytoskeletal structures and membranous
      organelles.
AB  - Dictyostelium discoideum cells produce five dynamin family proteins. Here, we
      show that dynamin B is the only member of this group of proteins that is
      initially produced as a preprotein and requires processing by mitochondrial
      proteases for formation of the mature protein. Our results show that dynamin B
      depletion affects many aspects of cell motility, cell-cell and cell-surface
      adhesion, resistance to osmotic shock, and fatty acid metabolism. The mature form
      of dynamin B mediates a wide range and unique combination of functions. Dynamin B
      affects events at the plasma membrane, peroxisomes, the contractile vacuole
      system, components of the actin-based cytoskeleton, and cell adhesion sites. The
      modulating effect of dynamin B on the activity of the contractile vacuole system
      is unique for the Dictyostelium system. Other functions displayed by dynamin B
      are commonly associated with either classical dynamins or dynamin-related
      proteins.

PMID- 21086151
TI  - Effects of shear on proteins in solution.
AB  - The effects of "shear" on proteins in solution are described and discussed.
      Research on this topic covers many decades, beginning with investigations of
      possible denaturation of enzymes during processing, whilst more recent concerns
      are how the quality of therapeutic proteins might be affected by shear or shear
      related effects. The paradigm that emerges from most studies is that shear in the
      fluid mechanical sense is unlikely by itself to damage most proteins and that
      interfacial phenomena are critically important. In particular, moving gas-liquid
      interfaces can be very deleterious. Aggregation of therapeutic proteins on
      nanoparticles shed from solid surfaces is a recent concern because of potential
      consequences on patient safety. It is clear that labeling such damage as "shear"
      is a mistake as this inhibits clear investigations of, and thinking about, the
      true causes of damage to proteins in solution during processing.

PMID- 21086152
TI  - Bottom-up preparation techniques for nanocrystals of lipophilic drugs.

PMID- 21086153
TI  - Utilize common criteria methodology for secure ubiquitous healthcare environment.
AB  - RFID technology is widely used in healthcare environments to ensure patient
      safety. Therefore, the testing of RFID tags, such as performance tests and
      security evaluations, is necessary to ensure inter-operational functional
      compatibility with standards. A survey of the literature shows that while
      standards that are around RFID performance tests have been addressed, but the
      same is not true for security evaluations. Therefore, in this paper, we introduce
      the Common Criteria security evaluation methodology, also known as ISO/IEC 15408,
      for the security evaluation of RFID tags and propose a framework as a minimal
      requirement for RFID tags to improve security assurance.

PMID- 21086150
TI  - Janus head: the dual role of HLA-G in CNS immunity.
AB  - The central nervous system (CNS) is considered an immune-privileged organ that
      maintains an adaptable immune surveillance system. Dysregulated immune function
      within the CNS contributes to the development of brain tumor growth, and robust
      immune activation results in excessive inflammation. Human lymphocyte antigen-G
      (HLA-G) proteins with tolerogenic immunoreactivity have been implicated in
      various pathophysiological processes including immune surveillance, governing
      homeostasis and immune regulation. In this review, we describe the wealth of
      evidence for the involvement of HLA-G in the CNS under physiological and
      pathological conditions. Further, we review regulatory functions that may be
      applicable as beneficial strategies in the therapeutic manipulation of immune
      mediated CNS immune responses. Additionally, we try to understand how this
      molecule cooperates with other CNS-resident cells to maintain normal immune
      homeostasis, while still facilitating the development of the appropriate immune
      responses.

PMID- 21086154
TI  - Caregiver reports of serious injuries in children who remain at home after a
      child protective services investigation.
AB  - The study objectives were to examine serious injuries requiring medical attention
      among children who remain at home after a child welfare/child protective services
      (CPS) maltreatment investigation in the US and to determine whether
      child/caregiver characteristics and ongoing CPS involvement are related to
      injuries requiring medical attention. Using the National Survey of Child and
      Adolescent Well-being, we analyzed data on the subsample of children who remained
      at home (N = 3,440). A multivariate logistic regression model included child
      characteristics, chronic illness and disability in the child, level of CPS
      involvement, subsequent foster care placement, caregiver characteristics, and
      caregiver/family psychological variables. Injuries requiring medical attention
      were identified in 10.6% of the in-home population over a 15-month period, with
      no differences in rates by age. Children with a chronic medical condition (OR =
      2.07; 95% CI, 1.20-3.58) and children with depressed caregivers (OR = 2.28; 95%
      CI, 1.45-3.58) were more likely to have an injury that required medical care.
      Older caregivers (>54 years) were less likely (OR = 0.15; 95% CI, 0.03-0.69) to
      have a child with an injury requiring care. Injuries were not related to further
      involvement with CPS after the initial maltreatment investigation. Children with
      chronic medical conditions who remained in their biological homes or whose
      caregivers were depressed were likely to experience an injury requiring medical
      attention. Older caregivers were less likely to report a child injury. Extending
      existing health policies for foster children to children who remain at home
      following referral to CPS may encourage more comprehensive injury prevention for
      this population.

PMID- 21086155
TI  - The association between inadequate gestational weight gain and infant mortality
      among U.S. infants born in 2002.
AB  - The purpose of this study was to determine the relative importance of inadequate
      gestational weight gain as a cause of infant mortality. Birth and infant death
      certificate data were obtained from a random sample of 100,000 records from the
      National Center for Health Statistics (NCHS) 2002 Birth Cohort Linked
      Birth/Infant Death Data File. Descriptive and proportional hazards regression
      analyses were used to assess the odds of infant mortality associated with
      inadequate gestational weight gain compared to normal weight gain. Nearly 30% of
      women experienced inadequate weight gain. Infants born to women with inadequate
      gestational weight gain had odds of infant death that were 2.23 times the odds
      for infants born to women with normal weight gain. Increased odds remained after
      adjustment for gestational age, low birth weight, maternal age, maternal
      education, and maternal race. Among racial or ethnic subgroups, African American
      women were 1.3 times as likely as white women to have an infant die, but they
      were no more likely to have an infant die than white women if they had inadequate
      weight gain. There is a substantial and significant association between
      inadequate gestational weight gain and infant death that does not differ by race,
      ethnic group membership, or maternal age.

PMID- 21086156
TI  - Exercise participation in adolescents and their parents: evidence for genetic and
      generation specific environmental effects.
AB  - Individual differences in adolescent exercise behavior are to a large extent
      explained by shared environmental factors. The aim of this study was to explore
      to what extent this shared environment represents effects of cultural
      transmission of parents to their offspring, generation specific environmental
      effects or assortative mating. Survey data on leisure-time exercise behavior were
      available from 3,525 adolescent twins and their siblings (13-18 years) and 3,138
      parents from 1,736 families registered at the Netherlands Twin Registry. Data
      were also available from 5,471 adult twins, their siblings and spouses similar in
      age to the parents. Exercise participation (No/Yes, using a cut-off criterion of
      4 metabolic equivalents and 60 min weekly) was based on questions on type,
      frequency and duration of exercise. A model to analyze dichotomous data from
      twins, siblings and parents including differences in variance decomposition
      across sex and generation was developed. Data from adult twins and their spouses
      were used to investigate the causes of assortative mating (correlation between
      spouses = 0.41, due to phenotypic assortment). The heritability of exercise in
      the adult generation was estimated at 42%. The shared environment for exercise
      behavior in adolescents mainly represents generation specific shared
      environmental influences that seem somewhat more important in explaining familial
      clustering in girls than in boys (52 versus 41%). A small effect of vertical
      cultural transmission was found for boys only (3%). The remaining familial
      clustering for exercise behavior was explained by additive genetic factors (42%
      in boys and 36% in girls). Future studies on adolescent exercise behavior should
      focus on identification of the generation specific environmental factors.

PMID- 21086157
TI  - Proceedings of the 15th International Symposium on Chromaffin Cell Biology: the
      chromaffin cell as a stress transducer. Nov 12-16th, 2009, Yucatan, Mexico.

PMID- 21086158
TI  - Effect of Roundup(r) (glyphosate formulation) in the energy metabolism and
      reproductive traits of Hyalella castroi (Crustacea, Amphipoda, Dogielinotidae).
AB  - Roundup((r)) (glyphosate formulation) is a nonselective and posts emergent
      herbicide used for controlling aquatic weeds and different concentrations are
      used in cultures around the world. The objective of this investigation was to
      examine the effects of Roundup((r)) (glyphosate formulation) on the biochemical
      composition, levels of lipoperoxidation, Na(+)/K(+)ATPase activity and
      reproductive traits in the Hyalella castroi. Amphipods were collected in summer
      2009, in the southern Brazilian highlands. In the laboratory, the animals were
      kept in aquariums under controlled conditions for 7 days, and after this period
      they were exposed to 0.36, 0.52, 1.08 and 2.16 mg/l of glyphosate for 7 days.
      After the period of exposure, the animals were immediately frozen for
      determination of glycogen, proteins, lipids, triglycerides, cholesterol, levels
      of lipoperoxidation, and Na(+)/K(+)ATPase activity. During each day of the
      cultivation reproductive traits (number of reproductive pairs, ovigerous females
      and eggs in the marsupium) were observed. All concentrations of Roundup((r))
      induced significant decreases in all biochemical parameters and Na(+)/K(+)ATPase
      activity, and significant increase in lipoperoxidation levels. Showing this form
      a potentially toxic effect at very low concentrations, this pattern of results
      can lead to significant changes in trophic structure of limnic environments
      because these amphipods are important links in food chain in these habitats.

PMID- 21086159
TI  - Fate and effects of ivermectin on soil invertebrates in terrestrial model
      ecosystems.
AB  - The effect of ivermectin on soil organisms was assessed in Terrestrial Model
      Ecosystems (TMEs). Intact soil cores were extracted from a pasture in England and
      kept for up to 14 weeks in the laboratory. Ivermectin was applied to the soil
      surface via spiked cow dung slurry at seven concentration rates ranging from 0.25
      to 180 mg/TME, referring to concentrations of 0.19-227 mg ivermectin/kg soil dry
      weight in the uppermost (0-1 cm) soil layer. After 7, 28 and 96 days following
      the application soil cores were destructively sampled to determine ivermectin
      residues in soil and to assess possible effects on microbial biomass, nematodes,
      enchytraeids, earthworms, micro-arthropods, and bait-lamina feeding activity. No
      significant effect of ivermectin was found for microbial respiration and numbers
      of nematodes and mites. Due to a lack of dose-response patterns no effect
      concentrations could be determined for the endpoints enchytraeid and collembolan
      numbers as well as total earthworm biomass. In contrast, EC50 values for the
      endpoint feeding rate could be calculated as 0.46, 4.31 and 15.1 mg ivermectin/kg
      soil dry weight in three soil layers (0-1, 0-5 and 0-8 cm, respectively). The
      multivariate Principal Response Curve (PRC) was used to calculate the
      NOEC(community), based on earthworm, enchytraeid and collembolan abundance data,
      as 0.33 and 0.78 mg ivermectin/kg soil dw for day 7 and day 96, respectively. The
      results shown here are in line with laboratory data, indicating in general low to
      moderate effects of ivermectin on soil organisms. As shown by the results of the
      bait-lamina tests, semi-field methods such as TMEs are useful extensions of the
      battery of potential test methods since complex and ecologically relevant
      endpoints can be included.

PMID- 21086160
TI  - Bilateral follicular cysts in a water buffalo.
AB  - The present short communication puts on record a case of bilateral, multiple
      follicular cysts in a water buffalo along with a detailed description of its
      ovarian biometry and follicular fluid composition. The ovarian weight and
      biometrical parameters were much higher than in normal cycling buffaloes. A total
      of three follicular cysts were observed, two on the right ovary and one on the
      left ovary, measuring 4.9, 3.0 and 2.6 cm yielding 21, 9 and 5 ml of follicular
      fluid, respectively. The cystic fluid was deep yellow in colour with a viscous
      consistency. The follicular fluid concentrations of glucose, total protein,
      cholesterol, acid phosphatase, calcium, phosphorus and progesterone in all the
      cysts were within the range reported previously in normal buffalo follicular
      fluid; however, the alkaline phosphatase concentration in cyst 1 and total
      bilirubin concentration in cysts 1 and 2 were higher than the values in normal
      follicular fluid. In contrast, the levels of urea nitrogen in cysts 1 and 3, and
      oestradiol in cyst 3 were lower than the normal values. All the three follicles
      had an oestradiol to progesterone ratio less than 1. The results of our study
      suggest that follicular cysts in buffalo are oestrogenically inactive and have an
      altered concentration of certain biochemical and hormonal constituents.

PMID- 21086161
TI  - Effect of climate factors on conception rate of lactating dairy cows in Mexico.
AB  - The purpose of this study was to investigate the relationship between conception
      rate (CR) and climate variables. Data consisted of 24,380 inseminations of
      Holstein dairy herd in Hidalgo, Mexico. Weather records, including daily
      temperature (T), relative humidity (RH), rainfall, wind speed, and solar
      radiation, were obtained from a nearby weather station. Means for each climatic
      variable from 2 days before artificial insemination (AI) to the AI day were
      calculated for each conception date represented in the study. A significant
      negative correlation was observed between the CR and mean and minimum T, mean and
      minimum RH, mean and minimum temperature-humidity index (THI), and rainfall. The
      overall mean CR was 34.3%. The CR in lactating dairy cows followed a seasonal
      pattern, lower CRs were observed in summer months than during winter (32.1% vs.
      36.9%; P<0.01). The variables that had the greatest influence on CR were minimum
      and maximum T, minimum RH, minimum THI, wind speed, and rainfall.

PMID- 21086162
TI  - Risk factors associated with prevalence of tuberculosis-like lesions and
      associated mycobacteria in cattle slaughtered at public and export abattoirs in
      Ethiopia.
AB  - This study was aimed at investigating risk factors associated with prevalence of
      tuberculosis (TB)-like lesions and associated mycobacteria in Ethiopian cattle
      slaughtered. The study was carried out during 2006-2007 in five selected
      municipal and export abattoirs. Methods of investigation involved detailed
      necropsy examination of carcasses and isolation of mycobacteria from pathologic
      tissue specimens. Factors of animal and environment origin were recorded and
      examined as explanatory variables in relation to the presence or absence of TB
      like lesions and the presence of viable mycobacteria. Multivariable logistic
      regression analysis was used to identify risk factors associated with prevalence
      of TB-like lesions and mycobacteria. Out of 3,322 carcasses inspected, 10.2% (95%
      confidence interval (CI) [9.2-11.3]) and 3.2% (95% CI [2.6-3.8]) were positive,
      respectively, based on necropsy and bacteriologic examinations. The highest and
      lowest lesion prevalence was recorded in Adama (24.7%) and Yabello (4.2%),
      respectively. Multivariable logistic regression analysis identified age, breed,
      abattoir location, geographic origin and management system as being risk factors
      for prevalence of TB-like lesions and occurrence of viable mycobacteria in
      Ethiopian cattle. The study demonstrated mycobacterial infection as important
      infectious disease of Ethiopian cattle. The reported confirmed cases of the
      disease in different management and geographic settings in Ethiopia disproved the
      earlier held opinion of its occurrence as a low sporadic profile. In view of a
      dietary proclivity of Ethiopian communities (milk and meat are predominantly
      consumed raw) and lifestyle (close contact of people with animals), the risk of
      bovine tuberculosis as a public health threat is eminent.

PMID- 21086163
TI  - Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti
      inflammatory effect on dextran sulfate sodium-induced colitis in mice.
AB  - BACKGROUND: Endogenous carbon monoxide (CO) is one of the three products of heme
      degradation by heme oxygenase-1 (HO-1) and exerts novel anti-inflammatory and
      anti-apoptotic effects as a gaseous second messenger. The purpose of this
      investigation was to determine whether exogenous CO could modulate intestinal
      inflammation. METHODS: Acute colitis was induced with 2% DSS in male C57BL/6
      mice. CO-releasing molecule-2 (CORM-2; tricarbonyldichlororuthenium(II) dimer)
      was intraperitoneally administered twice daily and the disease activity index
      (DAI) was determined. We measured tissue-associated myeloperoxidase (MPO)
      activity as an index of neutrophil infiltration, and the production of
      keratinocyte chemoattractant (KC) and tumor necrosis factor-alpha (TNF-alpha)
      protein in the intestinal mucosa. In an in-vitro study, young adult mouse colonic
      epithelial (YAMC) cells were incubated with TNF-alpha, and KC mRNA/protein
      expression and nuclear translocation of nuclear factor-kappa B (NF-kappaB) were
      measured with or without CORM-2 treatment. RESULTS: After DSS administration, DAI
      score increased in a time-dependent manner, and this increase was ameliorated by
      CORM-2 treatment. Increases in MPO activity and in the production of KC and TNF
      alpha after DSS administration were significantly inhibited by CORM-2. TNF-alpha
      induced KC production in YAMC cells was also inhibited by CORM-2 treatment.
      Further, nuclear translocation of NF-kappaB in YAMC cells was inhibited by CORM
      2. CONCLUSION: CORM-liberated CO significantly inhibited inflammatory response in
      murine colitis by inhibition of cytokine production in the colonic epithelium.
      These results suggest that CO could become a new therapeutic molecule for
      inflammatory bowel disease.

PMID- 21086164
TI  - miR-373 negatively regulates methyl-CpG-binding domain protein 2 (MBD2) in hilar
      cholangiocarcinoma.
AB  - BACKGROUND: microRNAs (miRNAs) are a class of non-coding, single-stranded RNA
      molecules that regulate gene expression at the posttranscriptional level. Methyl
      CpG-binding domain proteins (MBPs) are transcription repressors through binding
      to methylated gene promoters. Recent studies have shown that the effect of miRNAs
      on DNA methylation by targeting DNA methyltransferase (DNMTs) and/or MBPs plays
      an important role in various human cancers. AIMS: This study focuses on the
      regulation of MBPs by miR-373 and its downstream effect in hilar
      cholangiocarcinoma. METHODS: miR-373 was investigated by TaqMan miRNA Assay; mRNA
      and protein of MBD1, MBD2, and Mecp2 were determined by QuantiTect((r)) Primer
      Assays and Western blotting, respectively; RASSF1A mRNA was measured by SYBR
      Green real-time PCR; The targeting at MBD2-3'UTR by miR-373 was evaluated by dual
      luciferase reporter gene assay. RESULTS: miR-373 decreased and closely associated
      with poor cell differentiation, advanced clinical stage, and shorter survival in
      hilar cholangiocarcinoma; MBD2 exclusively over-expressed and reciprocally
      related to miR-373; precursor miR-373 inhibited the luciferase activity of MBD2
      3'UTR construct; exogenous miR-373 suppressed the expression of MBD2 and enhanced
      RASSF1A mRNA in QBC(939) cells; anti-miR-373 inhibitor up-regulated the
      expression of MBD2 and reduced RASSF1A mRNA in HIBEpic cells. CONCLUSIONS: miR
      373 is one negative regulator of MBD2. In hilar cholangiocarcinoma, down
      expression of miR-373 leads to increase of MBD2, which in turn suppresses the
      methylation-mediated gene such as RASSF1A.

PMID- 21086165
TI  - Characterization of expression in mice of a transgene containing 3.3 kb of the
      human lactase-phlorizin hydrolase (LPH) 5' flanking sequence.
AB  - BACKGROUND AND AIM: The regulation of human intestinal lactase-phlorizin
      hydrolase remains incompletely understood. One kb of pig and 2 kb of rat 5'
      flanking sequence controls correct tissue, cell, topographic, and villus LCT
      expression. To gain insight into human LCT expression, transgenic mouse lines
      were generated from 3.3 kb of human LPH 5' flanking sequence from a lactase
      persistent individual fused to a human growth hormone (hGH) reporter bounded by
      an insulator. METHODS: Four lines were identified in which reporter expression
      was specifically detectable in the intestine and no other organ, two of which
      demonstrated hGH expression specific to small and large intestine. Quantitative
      RT-PCR was carried out on proximal to distal segments of small intestine at fetal
      days 16.5 and 18.5 and at birth, postnatal days 7 and 28 in line 22. RESULTS: In
      fetal intestine, hGH expression demonstrated a proximal to distal gradient
      similar to that in native intestine. There was no significant difference between
      hGH expression levels at 7 and 28 days in segment 3, the midpoint of the small
      intestine, where expression of endogenous lactase is maximal at 7 days and
      declines significantly by 28 days. Distal small intestine displayed high levels
      of hGH expression in enteroendocrine cells, which were shown to be a subset of
      the PYY cells. CONCLUSIONS: Thus, a 3.3-kb LPH 5' flanking sequence construct
      from a lactase persistent individual is able to maintain postnatal expression in
      transgenic mice post weaning.

PMID- 21086166
TI  - Impact of acid suppression on upper gastrointestinal pH and motility.
AB  - BACKGROUND: Proton pump inhibitors (PPIs), widely prescribed to patients with
      upper gastrointestinal symptoms, alter intragastric pH, and may affect upper
      gastrointestinal transit and motility parameters in addition to affecting the
      ability to determine Wireless Motility Capsule (WMC) gastric emptying time. AIM:
      To assess PPI effect on motility parameters of the upper gastrointestinal tract
      and to determine if PPIs confound ability of WMC to measure gastric emptying
      time. METHODS: Twenty healthy subjects were treated with esomeprazole 40 mg bid
      for 1 week. Another 50 healthy subjects underwent evaluation in absence of PPIs.
      All subjects underwent WMC test after meal ingestion. After a rapid, sustained
      luminal pH rise >= 0.5 pH units, marking potential gastric emptying time of WMC,
      an abdominal X-ray (KUB) was taken for gastric emptying time confirmation. Mean
      pH, pressure and transit time were compared between PPI-treated and untreated
      groups. RESULTS: There was no difference in gastric emptying time, small bowel
      transit time (SBTT), or pressure profiles between the groups. The pH in all cases
      rose >= 0.5 pH units. Distal small bowel pH was significantly lower in subjects
      on PPIs. Gastric emptying time was identified in all subjects treated with PPIs.
      Pressure and slope criteria were developed to confirm the time of emptying.
      CONCLUSION: PPI therapy does not have a significant impact on upper
      gastrointestinal transit and motility but it does decrease distal small bowel pH.
      The medication reduced the magnitude of pH change at gastric emptying time but
      using additional criteria based on slope and contraction frequency, WMC was able
      to measure gastric emptying time in all patients treated with PPIs.

PMID- 21086167
TI  - Development and validation of a model to predict advanced fibrosis in chronic
      hepatitis B virus-infected patients with high viral load and normal or minimally
      raised ALT.
AB  - BACKGROUND/AIMS: Treating a group of chronic hepatitis B virus (HBV)-infected
      patients with high viral load and advanced fibrosis or cirrhosis, regardless of
      their serum alanine aminotransferase (ALT) levels, is recommended. The aim of
      this study was to derive and validate a model to predict advanced fibrosis in a
      cohort of patients with viral replication and normal or minimally raised ALT [ALT
      < 2 * upper normal limit (UNL)]. METHODS: Information was collected from 124
      patients who underwent liver biopsy. The diagnostic value of predictors was
      judged using multivariate logistic modeling and area under the receiver operating
      characteristic curves (ROC area). RESULTS: Advanced fibrosis (F3 or F4 on METAVIR
      scoring schema) was diagnosed in 45.7% (95% CI, 34-57.4%) of the patients of the
      derivation set (70 patients) and in 37% (95% CI, 24.2-49.9%) of the validation
      set (54 patients). In the derivation set, age and aspartate aminotransferase
      (AST) were independent clinical predictors of advanced fibrosis. The ROC areas of
      this Age-AST model were 0.8 (95% CI, 0.7-0.9) in the derivation set and 0.82 (95%
      CI, 0.71-0.93) in the validation set, respectively. Without missing a single
      case, this model identified 11 patients (20%) without advanced fibrosis in the
      validation set. CONCLUSIONS: A substantial proportion of patients with high viral
      load and ALT < 2 * UNL have advanced fibrosis. A simple model including age and
      AST is an easily applicable tool for physicians to guide their decisions on
      whether or not to perform liver biopsy in individual patients.

PMID- 21086168
TI  - Balloon-assisted enteroscopy with prophylactic polypectomy for Peutz-Jeghers
      syndrome: experience in Taiwan.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is a very rare disease that often causes
      severe complications such as bowel obstruction or gastrointestinal tract
      bleeding. In the past, it was usually treated by using surgical intervention
      despite the associated complications. Balloon-assisted enteroscopy (BAE) has been
      documented as an effective and safe method for the diagnosis and treatment of
      small bowel lesions. Hence, we conducted this study to verify whether BAE is
      useful for patients with PJS. AIM: To evaluate the safety and efficacy of BAE
      with prophylactic polypectomy in patients with PJS. METHODS AND PATIENTS: From
      August 2005 to February 2010, 6 consecutive patients were diagnosed with PJS
      after pathological and clinical examination, and underwent BAE examination and
      polypectomy at Chang Gung Memorial Hospital, an academic tertiary referral
      center. RESULTS: Six consecutive patients (4 men and 2 women) diagnosed with PJS
      underwent BAE with polypectomy. BAE was performed 17 times for complete
      examination of the entire small bowel. The range of the diameter of the removed
      polyps was 1-6 cm. No immediate complications such as hemorrhage or hollow organ
      perforation were noted during the procedure, and no patient developed
      intussusception during the follow-up period (32 +/- 17.5 months). CONCLUSION: BAE
      with polypectomy is useful for patients with PJS in order to reduce the
      complications of the condition.

PMID- 21086169
TI  - The sacrifice of knowledge: vain debates in the social scientific study of
      religion.
AB  - Since its inception, the social scientific study of religion has been a
      battleground for scholars advocating for the advantages of one sort of
      methodology over against the other. I argue that these debates have more to do
      with the personalities of the researchers rather than any kind of justifiable
      proof that one method is better than another. I argue that the process by which
      scholars quarrel over methods is a sign of stagnation or regression in the
      academy; I draw broad implications for the health of the discipline of religious
      studies.

PMID- 21086170
TI  - Religion and addiction.
AB  - Religion with its rituals can become an object of addiction, especially when a
      child while growing up experiences neglect and abuse. It is also very common that
      such individuals transfer their feelings of anger, rage and sometimes even true
      hatred to God. Then God becomes the substitute for their displaced vengeance
      (upon those who abused them as children).

PMID- 21086171
TI  - Religious involvement, psychosocial resourcefulness, and health.
AB  - A stratified randomized sample of 525 middle age (35-64 years old) men was used
      to study the relationships between self-reported level of church attendance (CA),
      self-reported religious faith (SRRF), religious well-being (RWB), existential
      well-being (EWB), self-actualization (SA), health, lifestyle, and participation
      in physical activity (PA). Religious measures (RWB, CA, and SRRF) were found to
      be dependent on psychosocial variables in terms of their relationships with PA,
      lifestyle, and health. On the other hand, psychosocial resourcefulness (SA, EWB,
      social support, and stress management) showed independent relationships with
      lifestyle, PA, and health. These findings indicate that the positive associations
      of psychological and sociological constructs with health are not related to or
      dependent upon ego syntonic religious identity.

PMID- 21086172
TI  - Lactobacillus plantarum surface layer adhesive protein protects intestinal
      epithelial cells against tight junction injury induced by enteropathogenic
      Escherichia coli.
AB  - Lactobacillus plantarum (LP) has previously been used for the treatment and
      prevention of intestinal disorders and disease. However, the role of the LP
      surface layer adhesive protein (SLAP) in inhibition of epithelial cell disruption
      is not fully understood. The aim of the present study was to investigate the
      protective effects of purified SLAP on Caco-2 cells infected with
      enteropathogenic Escherichia coli (EPEC). The role of ERK in LP-mediated
      inhibition of tight junction (TJ) injury was also evaluated in order to determine
      the molecular mechanisms underlying the protective effects of LP in epithelial
      cells. SLAP was extracted and purified from LP cells using a porcine stomach
      mucin-Sepharose 4B column. SLAP-mediated inhibition of bacterial adhesion was
      measured using a competition-based adhesion assay. Expression of TJ-associated
      proteins, maintenance of TJ structure, and levels of extracellular signal
      regulated kinase (ERK) and ERK phosphorylation were assessed in SLAP-treated
      cells by a combination of real-time PCR, western blotting, and immunofluorescence
      microscopy. Cell permeability was analyzed by measurement of trans-epithelial
      electrical resistance (TER) and dextran permeability. The effect of SLAP on
      levels of apoptosis in epithelial cells was assessed by flow cytometry. Results
      from these experiments revealed that treatment with SLAP decreased the level of
      adhesion of EPEC to Caco-2 cells. SLAP treatment also enhanced expression of TJ
      proteins at both the mRNA and protein levels and affected F-actin distribution.
      Although ERK levels remained unchanged, ERK phosphorylation was increased by SLAP
      treatment. Caco-2 cells treated with SLAP exhibited increased TER and decreased
      macromolecular permeability, which was accompanied by a decrease in the level of
      apoptosis. Together, these results suggest that LP-produced SLAP protects
      intestinal epithelial cells from EPEC-induced injury, likely through a mechanism
      involving ERK activation.

PMID- 21086173
TI  - The complete mitochondrial genome of the hard clam Meretrix meretrix.
AB  - Veneridae is a diverse, commercially important, and cosmopolitan family. Here we
      present the complete mitochondrial genome of the hard clam Meretrix meretrix
      (Bivalvia: Veneridae). The entire mitochondrial genome (mitogenome) sequence of
      M. meretrix is 19,826 bp in length, and contains 37 genes including 12 protein
      coding genes, 2 ribosomal RNAs, and 23 tRNAs. All genes are encoded on the heavy
      strand. In contrast to the typical animal mitochondrial genome, it lacks the
      protein-coding gene ATP8, and has only one copy of the tRNA(Ser) gene, but three
      duplications of the tRNA(Gln), which is the first report among the present
      molluscan mtDNAs. We observed that the gene arrangement between M. meretrix and
      M. petechialis is same except one more tRNAGln gene in M. meretrix., and the
      sequence similarity is as high as 99%, indicating that M. petechialis and M.
      meretrix could be treated as a junior synonym of M. meretrix. Maximum Likelihood
      and Bayeslan analysis of 12 concatenated protein-coding amino acid sequences
      place the Unionidae as a sister group to other bivalves, which reflects the
      general opinion that the Unionidae deverged very early in Bivalvia evolution.

PMID- 21086174
TI  - Molecular cloning and characterization of a vacuolar H+-pyrophosphatase from
      Dunaliella viridis.
AB  - The halotolerant alga Dunaliella adapts to exceptionally high salinity and
      possesses efficient mechanisms for regulating intracellular Na(+). In plants,
      sequestration of Na(+) into the vacuole is driven by the electrochemical H(+)
      gradient generated by H(+) pumps, and this Na(+) sequestration is one mechanism
      that confers salt tolerance to plants. To investigate the role of vacuolar H(+)
      pumps in the salt tolerance of Dunaliella, we isolated the cDNA of the vacuolar
      proton-translocating inorganic pyrophosphatase (V-H(+)-PPase) from Dunaliella
      viridis. The DvVP cDNA is 2,984 bp in length, codes for a polypeptide of 762
      amino acids and has 15 transmembrane domains. The DvVP protein is highly similar
      to V-H(+)-PPases from other green algae and higher plant species, in terms of its
      amino acid sequence and its transmembrane model. A phylogenetic analysis of V
      H(+)-PPases revealed the close relationship of Dunaliella to green algal species
      of Charophyceae and land plants. The heterologous expression of DvVP in the yeast
      mutant G19 (Deltaena1-4) suppressed Na(+) hypersensitivity, and a GFP-fusion of
      DvVP localized to the vacuole membranes in yeast, indicating that DvVP encodes a
      functional V-H(+)-PPase. A northern blot analysis showed a decrease in the
      transcript abundance of DvVP at higher salinity in D. viridis cells, which is in
      contrast to the salt-induced upregulation of V-H(+)-PPase in some plants,
      suggesting that the expression of DvVP under salt stress may be regulated by
      different mechanisms in Dunaliella. This study not only enriched our knowledge
      about the biological functions of V-H(+)-PPases in different organisms but also
      improved our understanding of the molecular mechanism of salt tolerance in
      Dunaliella.

PMID- 21086175
TI  - Apicidin suppresses transcription of 17beta-hydroxysteroid dehydrogenase type 1
      in endometrial adenocarcinoma cells.
AB  - It has recently been reported that endometrial cancer cells are able to convert
      estron (E1) to 17beta estradiol (E2). We observed the presence of 17beta
      hydroxysteroid dehydrogenase type 1 (HSD17B1) transcript and protein in receptor
      positive ER(+) and negative ER(-) Ishikawa endometrial adenocarcinoma (ISH)
      cells. ER(+) ISH, but not ER(-)02 ISH, cells were significantly susceptible to
      apicidin induced death, and we further used ER(-)ISH cells to study the effect of
      apicidin on cellular levels of HSD17B1 transcript and protein. We showed that
      apicidin significantly lowered HSD17B1 transcript and protein levels in ISH
      cells. There was no significant effect on HSD17B1 transcript stability. However,
      chromatin immunoprecipitation analysis revealed that apicidin significantly
      decreased occupation of the first exon of the HSD17B1 gene by Polymerase II.
      Since intratumoral E1 to E2 conversion is a significant contributor to the
      progression of estrogen dependent cancers, and HDAC inhibitors are being tested
      in anticancer clinical trials, our observations may have clinical value.

PMID- 21086177
TI  - The CSN1S1 N and F alleles identified by PCR-SSCP and their associations with
      milk yield and composition in Chinese dairy goats.
AB  - A method was depicted to identify null allele CSN1S1 N and low allele CSN1S1 F of
      the CSN1S1 gene of goat using PCR-SSCP (polymerase chain reaction-single strand
      conformation polymorphism). First, primer A was designed to amplify the exon 9 of
      CSN1S1 gene which produced three genotypes AA, AB, and BB. Among these three
      genotypes, only AA and AB individuals had a cytosine deletion at exon 9 after DNA
      sequencing, which cannot be used to identify the N and F alleles. Therefore,
      primer B was used to amplify intron 14 of CSN1S1 of described AA and AB
      individuals. Genotypes FF, FN and NN were detected within AA individuals and
      genotypes FO and NO were detected in the above AB individuals. The frequencies of
      F and N alleles in 708 samples from Xinong Saanen (XS) and Guanzhong (GZ) dairy
      goat breeds were 0.1139, 0.0927, and 0.2376, 0.1193, respectively. In 268 XS
      samples, the individuals with NN genotype contained a significant lower protein
      content than that of other genotypes (P<0.01). Individuals of FF genotype had
      significant higher milk yield than that of NO genotype in the first milk
      lactation of 202 XS individuals (P<0.05). Therefore, the variability at CSN1S1
      locus contains enough genetic diversity to be potentially useful in improving the
      quality and production of milk in Chinese dairy goat breeds.

PMID- 21086176
TI  - Human telomerase activity regulation.
AB  - Telomerase has been recognized as a relevant factor distinguishing cancer cells
      from normal cells. Thus, it has become a very promising target for anticancer
      therapy. The cell proliferative potential can be limited by replication end
      problem, due to telomeres shortening, which is overcome in cancer cells by
      telomerase activity or by alternative telomeres lengthening (ALT) mechanism.
      However, this multisubunit enzymatic complex can be regulated at various levels,
      including expression control but also other factors contributing to the enzyme
      phosphorylation status, assembling or complex subunits transport. Thus, we show
      that the telomerase expression targeting cannot be the only possibility to
      shorten telomeres and induce cell apoptosis. It is important especially since the
      transcription expression is not always correlated with the enzyme activity which
      might result in transcription modulation failure or a possibility for the gene
      therapy to be overcome. This review summarizes the current state of knowledge of
      numerous telomerase regulation mechanisms that take place after telomerase
      subunits coding genes transcription. Thus we show the possible mechanisms of
      telomerase activity regulation which might become attractive anticancer therapy
      targets.

PMID- 21086178
TI  - Transcript profiling of antioxidant genes during biotic and abiotic stresses in
      Panax ginseng C. A. Meyer.
AB  - The regulation of reactive oxygen scavengers against biotic and abiotic
      conditions were investigated in the seedling of Panax ginseng C. A. Meyer. From
      the EST library we selected the antioxidant marker genes such as superoxide
      dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione
      peroxidase (GPX), and glutathione synthase (GS). The abiotic chilling, heat,
      osmotic, oxidative, and wounding stresses and biotic stresses with fungal
      pathogens were tested against 3-week-grown seedlings. The expression patterns of
      the genes were analyzed by means of real-time quantitative RT-PCR. The
      transcriptome result under abiotic stresses showed differential expression and
      elevated up-regulation of PgSOD, PgGPX, PgGS, and PgAPX, thus it may prove the
      generation of ROS in ginseng. Whereas, in biotic stress the up-regulation of
      transcript level merely based on the incompatible interactions. But PgAPX and
      PgCAT showed no significant change or slight down-regulation of transcript level
      during pathogen interaction. Thus it may suggest that in ginseng, plant-pathogen
      interaction triggers defense-related gene transcription via salicylic acid
      mediated signaling mechanism, and also possess crosstalk signaling networks
      between abiotic and biotic stress responses.

PMID- 21086179
TI  - Chenopodium album pollen profilin (Che a 2): homology modeling and evaluation of
      cross-reactivity with allergenic profilins based on predicted potential IgE
      epitopes and IgE reactivity analysis.
AB  - The inhalation of Chenopodium album (C. album) pollen has been reported as an
      important cause of allergic respiratory symptoms. The aim of this study was to
      produce the recombinant profilin of C. album (rChe a 2) pollen and to investigate
      its cross-reactivity with other plant-derived profilins based on potential
      conformational epitopes and IgE reactivity analysis. Che a 2-coding sequence was
      cloned, expressed, and purified using one step metal affinity chromatography to
      recover high-purity target protein. We assessed cross-reactivity and predicted
      IgE potential epitopes among rChe a 2 and other plant-derived profilins.
      Immunodetection and inhibition assays using sixteen individual sera from C. album
      allergic patients demonstrated that purified rChe a 2 could be the same as that
      in the crude extract. The results of inhibition assays among rChe a 2 and other
      plant-derived profilins were in accordance with those of the homology of
      predicted conserved conformational regions. In this study, amino acid sequence
      homology analysis showed that a high degree of IgE cross-reactivity among plant
      derived profilins may depend on predicted potential IgE epitopes.

PMID- 21086180
TI  - Plasma lipids and lipoproteins in children and young adults with major beta
      thalassemia from western Iran: influence of genotype.
AB  - To determine the plasma lipid and lipoprotein profiles and their possible
      association with the type of beta-thalassemia mutation we studied 103 major beta
      thalassemia patients including 71 children and 32 young adults compared to 102
      healthy subjects consisted of 90 children and 12 young healthy adults. The plasma
      lipid and lipoprotein levels were measured by conventional methods. Considering
      all of the patients the levels of total cholesterol (TC), LDL-cholesterol (LDL
      C), and HDL-cholesterol (HDL-C) were significantly lower compared to controls.
      However, the level of TG was significantly higher in cases than controls.
      Comparing thalassemic patients homozygous for a beta0 type of mutation with those
      homozygous for a beta+ type of mutation (IVSI.110 G:A) indicated that the levels
      of LDL-C, TC were significantly increased and TG concentration tended to be
      higher in the latter patients. In conclusion, our study indicates that hemolytic
      stress results in hypocholesterolemia in major beta-thalassemia patients and the
      presence of more severe genotype in patients is correlated with more reduction in
      TG, TC, and LDL-C levels.

PMID- 21086181
TI  - Identification and expression of caspase-1 gene under heat stress in insecticide
      susceptible and -resistant Plutella xylostella (Lepidoptera: Plutellidae).
AB  - A caspase gene in Plutella xylostella (DBM) was identified firstly and named Px
      caspase-1. It had a full-length of 1172 bp and contained 900 bp open reading
      frame that encoded 300 amino acids with 33.6 kDa. The deduced amino acid of Px
      caspase-1 had two domain profile including caspase_p20 (position 61-184) and
      caspase_p10 (position 203-298) (i.e. the big and small catalytic domains), and
      the highly conserved pentapeptide QACQG in caspase_p20 domain (the recognized
      catalytic site of caspases). Being highly homologous to effector caspase genes in
      other insect and mammalian species, Px-caspase-1 was thought to be an effector
      caspase gene. Heat stress could result in significant mortality increase on adult
      DBM. Px-caspase-1 mRNA expression and caspase-3 enzyme activity (a effector
      caspase) were elevated with age and heat treatment. And, heat stress facilitated
      the procession of Px-caspase-1 expression. Significantly higher mRNA
      transcription levels were found in a chlorpyrifos-resistant DBM strain, as
      compared to those in insecticide-susceptible DBM. The results indicated that high
      temperature could significantly promote apoptosis process resulting in an the
      increased DBM mortality rate, and that insecticide-susceptible DBM had a
      significantly higher physiological fitness at high temperatures than insecticide
      resistant DBM.

PMID- 21086184
TI  - Psychometric properties of the Spanish form of the Schedule for Meaning in Life
      Evaluation (SMiLE).
AB  - OBJECTIVE: The objective of this study was to validate the Spanish version of the
      SMiLE (Schedule for Meaning in Life Evaluation). The SMiLE is a respondent
      generated instrument: respondents are first asked to list three to seven areas,
      which provide meaning to their lives, and then to rate their current satisfaction
      with the listed areas, as well as the individual importance of each one. Indices
      of total weighting (IoW), total satisfaction (IoS), and total weighted
      satisfaction (IoWS) are calculated. METHODS: Two hundred and fifty University
      students responded to the Spanish version of the SMiLE, as well as to instruments
      for measuring self-esteem, quality of life, depression, and anxiety. RESULTS: The
      Cronbach alphas (alpha = 0.61 for IoS and alpha = 0.41 for IoW) and test-retest
      correlations were comparable to those found in the initial validation of the
      instrument (IoS: r = 0.55; IoW: r = 0.61). The SMiLE showed positive correlations
      with self-esteem (r = 0.28, P < 0.05 for IoS) and the mental dimension of the
      quality of life scale (r = 0.31, P < 0.05 for IoS), while negative correlations
      were observed with depression (r = -0.23, P < 0.01) and anxiety (r = -0.17, P <
      0.05). CONCLUSIONS: The results support the validity of the Spanish version of
      the SMiLE as an instrument for assessing meaning in life.

PMID- 21086182
TI  - beta-Arrestins: multifunctional signaling adaptors in type 2 diabetes.
AB  - beta-arrestins are not only well-known negative regulators of G protein-coupled
      receptor (GPCR) signaling, but also important adaptors in modulating the strength
      and duration of cellular signaling by scaffolding and interacting with a lot of
      cytoplasmic proteins. While beta-arrestins are rather well described signal
      mediated molecules, they are not generally associated with insulin signaling. But
      recent work has confirmed the difference from original thought. The current
      review aims to explore the emerging roles for beta-arrestins in regulating
      insulin action, inflammatory signal pathway and other cellular signaling which
      are associated with type 2 diabetes.

PMID- 21086185
TI  - Depression and QOL in patients with ALS: how do self-ratings and ratings by
      relatives differ?
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative
      disease affecting the motor nervous system and currently lacking effective means
      of treatment. The focus of ALS treatment therefore lies in palliative treatment
      from a multidisciplinary team. Published findings regarding affective components
      and patients' perceived quality-of-life (QoL) as well as comparative reports of
      family members/caregivers remain equivocal. METHODS: In this study, 41 ALS
      patients and their relatives were enrolled in a study employing the 12-item ALS
      Depression-Inventory (ADI-12) and the Munich quality-of-life dimensions list
      (MLDL). The ALS-functional rating scale (ALSFRS-R) was used to evaluate physical
      disabilities. RESULTS: The ADI-12 depression scale data identified nine patients
      with depressive disorders; the patients had satisfactory QoL outcomes on the
      MLDL. The results did not differ significantly between ALS patients and their
      relatives. CONCLUSIONS: Thus, in agreement with other studies, QoL and emerging
      depression do not automatically coincide with patients' physical impairments of
      the patients. This "well-being paradox" is currently not well understood, and
      further studies are needed to optimize the treatment of patients through the
      course of disease progression.

PMID- 21086186
TI  - Melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in
      leukocytes from elderly humans.
AB  - The mechanisms regulating neutrophil apoptosis are basically unaffected by the
      aging process. However, a significant impairment of cell survival occurs in
      elderly individuals following neutrophil challenge with pro-inflammatory stimuli,
      such as granulocyte-macrophage colony-stimulating factor (GM-CSF). The goal of
      the present study was to prove the effects of melatonin supplementation on
      apoptosis induced by calcium signaling in human leukocytes from elderly
      volunteers. Treatments with the specific inhibitor of cytosolic calcium re
      uptake, thapsigargin, and/or the calcium mobilizing agonist, N-formyl-methionyl
      leucyl-phenylalanine (fMLP), induced mitochondrial membrane depolarization,
      caspase activation, phosphatidylserine (PS) externalization, and DNA
      fragmentation in leukocytes from both young and elderly volunteers, although such
      effects were much more evident in aged leukocytes. Importantly, melatonin
      treatment substantially preserved mitochondrial membrane potential, reversed
      caspase activation, reduced PS exposure and forestalled DNA fragmentation in
      leukocytes from both age groups. In conclusion, melatonin is able to delay
      endoplasmic reticulum stress-induced apoptosis in aged leukocytes and may
      counteract, at the cellular level, age-related degenerative phenomena linked to
      oxidative stress.

PMID- 21086187
TI  - In vitro growth of microsporidia Anncaliia algerae in cell lines from warm water
      fish.
AB  - Anncaliia algerae is an aquatic microsporidium that most commonly infects
      mosquitoes but can be grown on the rabbit kidney cell line, RK-13. Spores were
      purified from RK-13 cultures and added to cell lines from warm water fish and
      from an insect. The cell lines were GFSK-S1 and GFB3C-W1 from goldfish skin and
      brain respectively, ZEB2J from zebrafish embryos, FHMT-W1 from fathead minnow
      testis, and Sf9 from ovaries of a fall armyworm moth. All cultures were
      maintained at 27 degrees C. Infection was judged to have taken place by the
      appearance of sporonts and/or spores in cells and occurred in all cell lines.
      Spores were also isolated from ZEB2J cultures and used to successfully infect new
      cultures of ZEB2J, RK-13 and Sf9. These results suggest that cells of a wide
      range of vertebrates support A. algerae growth in vitro and fish cells can
      produce spores infectious to cells of mammals, fish, and insects.

PMID- 21086188
TI  - Identification of differentially expressed genes in lung tissues of nickel
      exposed rats using suppression subtractive hybridization.
AB  - Occupational exposure to nickel compound, such as nickel refining,
      electroplating, and in conjunction with other metals, is harmful to the health,
      causing respiratory distress, and lung and nasal cancer. In this work, the
      different gene expression patterns of lung tissues from nickel-exposed rats and
      controls were investigated. The suppression subtractive hybridization (SSH)
      method was used to generate two subtracted cDNA libraries with gene transcripts
      differentially expressed after nickel inducing. Dot-blot hybridizations were used
      to confirm differential ratios of expression of obtained SSH clones. Out of 768
      unique SSH clones, which were chosen randomly from the two subtraction libraries
      (384 of each), 319 could be verified as differentially expressed. According to
      blast screening and functional annotation, 28% genes in nickel-induced cDNA
      library were related to cell differentiation, whereas 21% in driver library were
      related to oxygen transport. Two novel expressed sequence tags (ESTs; NCBI
      Accession No. FC809414 and No. FC809411) in nickel-induced cDNA library were
      obtained. The genes detected in the present study are probably important genes
      associated with nickel-induced lung cancer.

PMID- 21086189
TI  - Advantages of the use of deciduous teeth, hair, and blood analysis for lead and
      cadmium bio-monitoring in children. A study of 6-year-old children from Krakow
      (Poland).
AB  - The population of about 300 6-year-old preschool children was studied for lead
      (Pb) and cadmium (Cd) in deciduous teeth, scalp hair, and capillary blood. Zinc
      (Zn) content in hair was also measured due to its possible interferences with the
      elements studied. The Pb and Cd contents were measured by graphite furnace atomic
      absorption spectrometry with Zeeman background correction, and Zn, by flame
      method. Metal levels found were comparable to those in European countries.
      Positive correlations between Pb and Cd in the same and different tissues were
      widespread (r=0.23-0.68). A positive correlation was found between Pb in teeth
      and blood (r=0.65, p<0.001). Pb blood threshold 100 MUg L(-1) referred to 2.6 MUg
      g(-1) Pb in teeth. Predictability of this Pb teeth limit was 14% vs. 5% for Pb
      blood. Strong negative correlation was found between hair Pb and Zn (r=-0.68,
      p<0.001). Enhanced Cd and Zn levels in hair were associated with the household
      drinking water hardness. The associations with some other environmental and
      behavioral factors were also presented and discussed. The results proved the
      advantage of analysis of primary teeth for Pb exposure screening of preschool
      children.

PMID- 21086190
TI  - Effects of aminoguanidine and vitamin C on collagen type IV in diabetic
      nephropathy rats.
AB  - The aim of this article is to investigate the effects of Aminoguanidine and
      vitamin C (VitC) on type IV collagen in diabetic nephropathy rats. Diabetic
      nephropathy rats were induced by intraperitoneal injection of STZ. Rats were
      randomly divided into five groups: normal control group (n = 10), diabetes group
      (n = 10), aminoguanidine group (n = 10), VitC group (n = 10), aminoguanidine and
      VitC group (n = 10). After 16 weeks, the general conditions, blood gloucose,
      glycosylated hemoglobin, blood urea nitrogen, serum creatinine, serum type IV
      collagen, urinary albumin excretion rate, and creatinine clearance rate were
      detected, type IV collagen protein was determined by immunohistochemical analysis
      as well as the expression of collagen type IValpha1 mRNA were determined by in
      situ hybridization analysis in the kidneys of each group. The results were (1)
      diabetes mellitus and renal lesions occurred in the diabetes group,
      aminoguanidine group, VitC group, VitC and aminoguanidine group; (2)
      aminoguanidine and VitC improved the general conditions of diabetic nephropathy
      rats, decreased blood urea nitrogen, serum creatinine, and urinary albumin
      excretion rate as well as increased creatinine clearance rate. The expressions of
      collagen type IV were significantly down-regulated in treatment groups in
      contrast to the diabetes group. Aminoguanidine and VitC protect renal lesions in
      diabetic nephropathy, respectively, by inhibiting expression of type IV collagen,
      while aminoguanidine and VitC have a synergistic effect on them.

PMID- 21086191
TI  - Traumatic subarachnoid hemorrhage and the COL3A1 gene: emergence of a potential
      causal link.
AB  - We describe two previously unreported associations in four cases. The first two
      cases demonstrate an association between segmental mediolytic arteriopathy and
      vascular Ehlers-Danlos syndrome. The second two cases illustrate an association
      between vascular Ehlers-Danlos syndrome and traumatic subarachnoid hemorrhage. In
      case 1, there was acute subarachnoid hemorrhage and mesenteric artery dissection.
      In case 2, there was an acute mesenteric artery dissection with intestinal
      infarction. In both cases 1 and 2, segmental mediolytic arteriopathy was found in
      the vertebral arteries. Cases 3 and 4 were sudden deaths from traumatic
      subarachnoid hemorrhage with intracranial vertebral artery rupture. Genetic
      testing in all four cases revealed point mutations in the type 3 procollagen gene
      (COL3A1), as observed in vascular Ehlers-Danlos syndrome. Based on the first two
      cases, we propose that segmental mediolytic arteriopathy may be a marker for this
      disease. We further suggest that vascular Ehlers-Danlos syndrome may be related
      to the pathogenesis of traumatic vertebral artery injury, in some cases. We
      recommend that cases of segmental mediolytic arteriopathy and traumatic
      subarachnoid hemorrhage undergo genetic testing for COL3A1 mutations.

PMID- 21086192
TI  - Response assessment in neuro-oncology.
AB  - Accuracy and reproducibility in determining response to therapy and tumor
      progression can be difficult to achieve for nervous system tumors. Current
      response criteria vary depending on the pathology and have several limitations.
      Until recently, the most widely used criteria for gliomas were "Macdonald
      criteria," based on two-dimensional tumor measurements on neuroimaging studies.
      However, the Response Assessment in Neuro-Oncology (RANO) Working Group has
      published new recommendations in high-grade gliomas and is working on
      recommendations for other nervous system tumors. This article reviews current
      response criteria for high-grade glioma, low-grade glioma, brain metastasis,
      meningioma, and schwannoma.

PMID- 21086193
TI  - Primary prevention of variceal hemorrhage.
AB  - Variceal hemorrhage is one of the leading causes of death in patients with
      cirrhosis, with the 6-week mortality after each episode ranging from 15% to 20%.
      The two main strategies for primary prevention of variceal bleeding in patients
      with cirrhosis and varices are the administration of nonselective beta-blockers
      or the obliteration of varices with use of endoscopic band ligation. In this
      review, we present and critically review the latest data on primary prevention of
      variceal hemorrhage. We advocate that nonselective beta-blockers should be the
      first line therapy, and band ligation should be offered only in cases of
      intolerance or side effects. We also explore potential future therapies based on
      preliminary experimental and clinical data.

PMID- 21086194
TI  - Treatment of localized extranodal NK/T cell lymphoma, nasal type.
AB  - Extranodal NK/T cell lymphoma predominantly presents as a localized disease in
      the upper aerodigestive tract from the nasal cavity to the hypopharynx. Because
      radiotherapy has better outcomes than chemotherapy with reduced locoregional
      failure, it should be considered the preferred first-line therapy. However, the
      addition of chemotherapy is appropriate as part of the initial treatment because
      of the frequent systemic progression or relapse after radiotherapy. At present,
      the combination of radiotherapy and chemotherapy can be considered an effective
      treatment option, and the promising results of recent prospective studies with
      concurrent chemoradiotherapy support this treatment strategy. In contrast,
      intensive chemotherapy should be considered as initial treatment for patients
      with tumors in non-upper-aerodigestive-tract sites, such as skin or intestine
      because they usually progress to systemic disease. Likewise, for patients with
      poor prognostic factors, such as a high NK lymphoma prognostic index, autologous
      stem cell transplantation during remission and additional treatments with central
      nervous system prophylaxis may be beneficial. However, the precise role of these
      treatments needs to be clarified further by prospective clinical trials. Thus, a
      prospective study is warranted to explore a risk-adapted treatment strategy of
      applying initial chemoradiotherapy and additional consolidation treatments.

PMID- 21086195
TI  - Risk factors for revision of hip arthroplasties in patients younger than 30
      years.
AB  - BACKGROUND: Numerous reports of THAs in patients younger than 30 years indicate a
      high risk of revision. Although risk factors for revision have been reported for
      older patients, it is unclear whether these risk factors are the same as those
      for patients younger than 30 years. QUESTIONS/PURPOSES: We therefore (1)
      determined function and survivorship of revision THAs performed in patients
      younger than 30 years, and (2) assessed the risk factors for revision THAs in
      this younger population by comparison with a group of patients younger than 30
      years who did not undergo revision. PATIENTS AND METHODS: We retrospectively
      reviewed the clinical records and radiographs of 55 patients younger than 30
      years (average age at revision, 24.3 years; range, 14-30 years) who underwent 77
      hip revisions. Revision was performed, on average, 4.6 years (range, 0.4-12
      years) after the primary THA. The results for these 55 patients (77 revision
      THAs) were compared with results for a nonrevised group, including 819 THAs in
      patients younger than 30 years. Minimum followup of the revision group was 1 year
      (mean, 6.2 years; range, 1-15 years). RESULTS: At followup after the revision,
      the Merle d'Aubigne-Postel score improved from 12.2 to 14.6. The rates of
      dislocation, neurologic lesions, and fractures were 15%, 7.8%, and 14%,
      respectively. The 10-year survival rate was 36% (95% confidence interval [CI],
      21%-51%). Compared with the nonrevised group, the independent revision risk
      factors were young age at primary THA (OR 1.14 [1.07-1.19]), high number of
      previous surgeries (OR 5.41 [2.67-10.98]), and occurrence of at least one
      dislocation (OR 3.98 [1.74-9.07]). Hard-on-soft bearings had a higher risk (OR
      3.42 [1.91-6.1]) of revision compared with hard-on-hard bearings. CONCLUSIONS:
      Revision THAs are likely in patients younger than 30 years, and the complication
      rate is high. The survivorship of hip revision in this population is low and
      alternative solutions should be advocated whenever possible. LEVEL OF EVIDENCE:
      Level III, therapeutic study, case control study. See the Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 21086196
TI  - Biographical sketch: George L. Walton, MD and Walter E. Paul, MD.
AB  - This biographical sketch on George L. Walton and Walter E. Paul corresponds to
      the historic text, The Classic: Contribution to the Study of Spinal Surgery: One
      Successful and One Unsuccessful Operation for Removal of Tumor (1905), available
      at DOI 10.1007/s11999-010-1664-2 .

PMID- 21086197
TI  - Cerebellar long-term depression is deficient in Niemann-Pick type C disease mice.
AB  - Niemann-Pick type C disease (NPC) is an autosomal recessive lipidosis
      characterized by progressive neurodegeneration. Although several studies have
      revealed unusual accumulation of unesterfied cholesterol in astrocytic lysosome
      of NPC, pathophysiological basis of cerebellar neuronal dysfunction remains
      unclear. We compared parallel fiber-Purkinje cell synaptic transmission and long
      term depression (LTD) in +/+npc (nih) (npc(+/+)) and -/-npc(nih) (npc(-/-)) mice.
      Our data showed that adenosine A1 receptor agonists decreased parallel fiber
      excitatory postsynaptic current (EPSC) amplitude and mEPSC frequency while its
      antagonists increased EPSC amplitude and mEPSC frequency in wild type and mutant
      mice. Furthermore, parallel fiber LTD was deficient in npc(-/-) mice and
      supplement of adenosine triphosphate (ATP) rescued the impaired LTD. Taken
      together, these experiments suggest that synaptic strength and LTD are altered in
      npc(-/-) mice due to the decrease of ATP/adenosine release and deactivation of A1
      receptors in parallel fiber terminals. The enhanced synaptic transmission and the
      decreased LTD might result in progressive neurotoxicity of Purkinje cells in npc(
      /-) mice.

PMID- 21086198
TI  - In vitro study of the antioxidative properties of the glucose derivatives against
      oxidation of plasma components.
AB  - Oxidative stress has been implicated in the pathogenesis of variety of diseases.
      Since the endogenous antioxidant defense may be not adequate to counteract the
      enhanced generation of oxidants, a growing interest in research for exogenous
      nutrients has been observed. The present study was designed to assess in vitro
      the antioxidative properties of the glucose derivatives: calcium D-glucarate, D
      gluconic acid lactone, and sodium D-gluconate (0.5-3 mM) in the protection of
      plasma proteins and lipids, against the damage caused by 0.1 mM peroxynitrite
      (ONOO-). Exposure of plasma to ONOO- resulted in carbonyl groups increase, 3
      nitrotyrosine (3-NT) formation, reduction in thiol groups, and enhanced lipid
      peroxidation. D-gluconic acid lactone and sodium D-gluconate effectively
      decreased 3-NT formation; the antinitrative action of calcium D-glucarate was
      less effective. In plasma samples incubated with ONOO- and tested compounds, the
      level of carbonyl groups was decreased in comparison to plasma samples treated
      only with ONOO-. The level of protein -SH groups and glutathione was
      significantly higher in the presence of glucose derivatives than in plasma
      samples treated with ONOO- only. All the tested compounds had the inhibitory
      effect on the peroxynitrite-induced plasma lipids peroxidation. The results
      obtained from our work indicate that calcium D-glucarate, D-gluconic acid
      lactone, and sodium D-gluconate may partly protect plasma proteins and lipids
      against peroxynitrite-induced damages.

PMID- 21086199
TI  - Involvement of rat gonadotrope progesterone receptor in the ovary-mediated
      inhibitory action of FSH on LH synthesis.
AB  - Rat ovaries stimulated with human follicle-stimulating hormone (hFSH) overexpress
      a factor that attenuates the LH surge in the rat: the putative gonadotropin surge
      attenuating factor (GnSAF). A reduced gondadotrope progesterone receptor (PR)
      phosphorylation/activation is likely to be the main causative factor involved in
      GnSAF bioactivity on LH release. Besides, GnSAF reduces LH synthesis as well as
      LH secretion, and it is not known whether PR is involved in the inhibitory action
      of GnSAF on LH synthesis. Thus, the purpose of the present work was to evaluate
      the involvement of PR in the inhibitory effects of GnSAF on LH synthesis in
      cycling rats. To this end we used a specific radioimmunoassay and reverse
      transcription-polymerase chain reaction (RT-PCR) to study the effect on LH
      pituitary content and LHbeta mRNA expression of PR occupancy with P (3 mg/0.2 ml
      oil in diestrus) on the inhibitory effects of hFSH (0, 0.1, 1, and 10 IU) in
      metestrus (day 2) and diestrus (day 3) on LH synthesis on proestrus in intact and
      on day 4 in day 2 ovariectomized (OVX) rats injected with 5 and 10 MUg of
      estradiol benzoate (EB) on days 2 and 3, respectively. Results showed that (1)
      hFSH decreased pituitary LH content in intact, but not in OVX rats injected with
      EB, without affecting LHbeta mRNA levels, and (2) PR occupancy with P annulled
      the inhibitory action of hFSH on pituitary LH content. These results indicate
      that PR is involved in ovarian GnSAF effect on LH content probably at a post
      transcriptional level.

PMID- 21086200
TI  - The Year of the Lung: outdoor air pollution and lung health.
AB  - With reference to the Year of the Lung, current knowledge of the respiratory
      effects of current ambient air pollution is reviewed. Acute respiratory effects
      are well established. Studies such as SAPALDIA and others now shed light on the
      long-term effects on chronic pathologies and on the health benefit of air quality
      improvements. The identification of those at highest risk and of local effects of
      not yet regulated traffic-related pollutants remains a research priority.

PMID- 21086201
TI  - Childhood overweight and obesity: good news or is the worst still to come?

PMID- 21086202
TI  - 2010, International Year of the Lung.

PMID- 21086203
TI  - Chlamydia trachomatis infection in a Swiss prison: a cross sectional study.
AB  - BACKGROUND: Chlamydia trachomatis infection (CTI) is the most frequent sexually
      transmitted infection in Switzerland and its prevalence in correctional settings
      is currently unknown. The aim of this study was to determine the prevalence of
      CTI and associated risk factors in a population of inmates aged 18-35 years.
      METHODS: Inmates attending the health care unit of the largest Swiss remand
      prison from June 2008 to May 2009 were invited to participate in this cross
      sectional study. All participants completed a questionnaire and provided a first
      void urine specimen for CTI testing based on a PCR assay. Univariate and
      multivariate logistic regression analyses were used to assess risk factors
      associated with CTI. RESULTS: 214 male and 20 female inmates agreed to
      participate. Overall CTI prevalence was 6.5% in men (95% CI 3.2; 9.9) and 10%
      (95%CI 0; 23.1) in women. None of the following possible risk factors analysed
      were significantly correlated to CTI: age, origin, education, religion, number of
      sexual partners, iv drug use, subjective health status and uro-genital symptoms.
      CONCLUSION: CTI prevalence in the largest Swiss prison was two to six times
      higher than in the general population but similar to other European prison
      settings. This result should raise our awareness that this population is at
      particularly high risk for sexually transmitted infections and motivate a
      widespread surveillance of prison CT prevalence. We hesitate to consider
      systematic screening because evidence is still lacking in relation to the
      benefits of screening in males. Local cost effectiveness studies would highly
      contribute to a correct decision concerning implementation of screening.

PMID- 21086204
TI  - The impact of infections on critically ill acute heart failure patients: an
      observational study.
AB  - BACKGROUND: Hospitalised patients with acute heart failure (AHF) suffer from a
      high morbidity and mortality, which might, at least partly, be influenced by
      concomitant infections. The aim of this observational study was to investigate
      the impact of infections on the clinical course of critically ill patients with
      AHF, both present on intensive care unit (ICU) admission and acquired during the
      ICU stay. METHODS: From 178 consecutive AHF patients, 76 were treated medically
      and 21 required emergency cardiac surgery. The remaining 81 patients, who
      underwent elective cardiac surgery, were excluded from the assessment of
      infections on ICU admission, but were included in the analysis of nosocomial
      infections during the ICU stay. RESULTS: A total of 16% of patients (16/97) had
      infections on ICU admission. These patients had longer ICU (6 vs. 3 days, p =
      0.04) and hospital (19 vs. 11 days, p = 0.04) stays than patients without
      infections. Although not statistically significant, there was a trend for
      increased mortality at 30 days (44% vs. 24%, p = 0.13) and 6 months (57% vs. 31%,
      p = 0.13) in AHF patients with infections on ICU admission. Infection
      complications during the ICU stay occurred in 17% (30/178) of AHF patients and
      significantly increased their mortality at 30 days (33% vs. 14%, p = 0.02) and 6
      months (41% vs. 18%, p = 0.02). CONCLUSIONS: In this observational study,
      infections present on ICU admission or occurring during the ICU stay had a
      negative impact on the morbidity and mortality of critically ill patients with
      AHF. Future studies are needed to gain a better understanding of the interactions
      between heart failure and infections, as a better knowledge of this field may
      have an important therapeutic potential.

PMID- 21086205
TI  - Can the size of the epiphysis determine the number of secondary ossification
      centers? A mathematical approach.
AB  - Previous studies have concluded that the chemical feedback (loop) between two
      reagent molecular factors through a reaction-diffusion mechanism could explain
      the stable spatial pattern found in the origin of the secondary ossification
      centres (SOCs). Furthermore, the emergence of the SOC may depend on the size and
      shape of the head of the bone, as observed in different animals. In this paper,
      we develop new computer simulations that study the effect of the size of the
      epiphysis on the emergence of the SOC. This study determines two or more SOCs,
      that may appear in the head of long bones, depending on the size of the
      epiphysis.

PMID- 21086206
TI  - FSI simulation of asymmetric mitral valve dynamics during diastolic filling.
AB  - In this article, we present a fluid-structure interaction algorithm accounting
      for the mutual interaction between two rigid bodies. The algorithm was used to
      perform a numerical simulation of mitral valve (MV) dynamics during diastolic
      filling. In numerical simulations of intraventricular flow and MV motion, the
      asymmetry of the leaflets is often neglected. In this study the MV was rendered
      as two rigid, asymmetric leaflets. The 2D simulations incorporated the dynamic
      interaction of blood flow and leaflet motion and an imposed subject-specific,
      transient left ventricular wall movement obtained from ultrasound recordings. By
      including the full Jacobian matrix in the algorithm, the speed of the simulation
      was enhanced by more than 20% compared to using a diagonal Jacobian matrix.
      Furthermore, our results indicate that important features of the flow field may
      not be predicted by the use of symmetric leaflets or in the absence of an
      adequate model for the left atrium.

PMID- 21086207
TI  - A numerical model of the fracture healing process that describes tissue
      development and revascularisation.
AB  - A dynamic model was developed to simulate complex interactions of mechanical
      stability, revascularisation and tissue differentiation in secondary fracture
      healing. Unlike previous models, blood perfusion was included as a spatio
      temporal state variable to simulate the revascularisation process. A 2D,
      axisymmetrical finite element model described fracture callus mechanics. Fuzzy
      logic rules described the following biological processes: angiogenesis,
      intramembranous ossification, chondrogenesis, cartilage calcification and
      endochondral ossification, all of which depended on local strain state and local
      blood perfusion. In order to evaluate how the predicted revascularisation
      depended on the mechanical environment, we simulated two different healing cases
      according to two groups of transverse metatarsal osteotomies in sheep with
      different axial stability. The model predicted slower revascularisation and
      delayed bony bridging for the less stable case, which corresponded well to the
      experimental observations. A revascularisation sensitivity analysis demonstrated
      the potential of the model to account for different conditions regarding the
      blood supply.

PMID- 21086208
TI  - Health effects of an efficient vented stove in the highlands of Guatemala.
AB  - In Guatemala, as in many places throughout the world, millions of indigenous
      people cook over non-ventilated indoor open fires. Indoor air pollution and
      accidental burns are well-known problems attributed to such fires. Efforts have
      been made to improve health outcomes by placing more efficient vented stoves in
      homes to decrease such exposure. The purpose of this study is to see if there are
      any measurable improvements in health outcomes after placement of such stoves
      within a community. Specifically, this study is designed to evaluate the health
      effects of placement of the ONIL stove, a rocket-style stove that has been shown
      to decrease household carbon monoxide (CO) levels and wood-fuel use. The ONIL
      stove was installed in more than 90% of the homes in Santa Avelina, Quiche,
      Guatemala between 2002 and 2006. The number of clinic visits per year for acute
      upper- and lower-respiratory illnesses in this village was compared for the years
      2002 and 2006. Clinic visits for upper- and lower-respiratory illnesses combined
      decreased by 26%, and for acute lower respiratory solely, by 45% between 2002 and
      2006. This study suggests that the placement of an improved vented stove may be
      associated with a corresponding decrease in acute respiratory illnesses.

PMID- 21086209
TI  - Correlates of consumer trust in online health information: findings from the
      health information national trends survey.
AB  - The past few decades have witnessed a dramatic increase in consumers seeking
      health information online. However, the quality of such information remains
      questionable, and the trustworthiness of online health information has become a
      hot topic, whereas little attention has been paid to how consumers evaluate
      online health information credibility. This study builds on theoretical
      perspectives of trust such as personal-capital-based, social-capital-based, and
      transfer-based, and it examines various correlates of consumer trust in online
      health information. The author analyzed the 2007 Health Information National
      Trends Survey data (N = 7,674). Results showed that consumer trust in online
      health information did not correlate with personal capital such as income,
      education, and health status. Social capital indicated by visiting social
      networking Web sites was not associated with trust in online health information
      either. Nevertheless, trust in online health information transferred from
      traditional mass media and government health agencies to the Internet, and it
      varied by such information features as easiness to locate and to understand. Age
      appeared to be a key factor in understanding the correlates of trust in online
      health information. Theoretical and empirical implications of the results are
      discussed.

PMID- 21086210
TI  - Social influence of a religious hero: the late Cardinal Stephen Kim Sou-hwan's
      effect on cornea donation and volunteerism.
AB  - This study examined the mediated influence of a celebrated religious hero in
      South Korea, Cardinal Stephen Kim, through two forms of involvement--parasocial
      interaction and identification--on intention toward cornea donation and
      volunteerism, and it investigated how the news media diffused of his death. A
      structural equation modeling analysis with a Web-based voluntary survey of more
      than 1,200 people in South Korea revealed a multistep social influence process,
      beginning with parasocial interaction with Cardinal Kim, leading to
      identification with him, which predicted intention toward cornea donation and
      volunteerism. Additional investigations found that news of Cardinal Kim's death
      diffused rapidly through media and interpersonal communication. Results of this
      study demonstrate that religious leaders who achieve a celebrity hero status can
      prompt public discussion of important issues rather quickly through extensive
      media coverage, enabling them to promote prosocial behavior and positively affect
      public health.

PMID- 21086211
TI  - Energy and macronutrient intake in adolescent sprint athletes: a follow-up study.
AB  - Macronutrient intake, height, weight, and body composition of 60 adolescent
      sprint athletes were estimated every 6 months over 3 years. Seven-day food
      records were analysed based on the Belgian and Dutch food databanks. The age of
      participants at the start of the 3-year study was 14.8 +/- 1.6 years for female
      athletes and 14.7 +/- 1.9 years for male athletes. Girls and boys gained height
      (3.4 +/- 4.6 cm and 5.9 +/- 6.6 cm respectively) and weight (5.6 +/- 3.5 kg and
      8.7 +/- 5.5 kg respectively), whereas percent body fat remained unchanged in both
      girls and boys (around 17.0% and 8.5% respectively). Mean protein intake of
      around 1.5 g . kg-1 body weight was within recommendations on each occasion for
      both sexes. Carbohydrate intakes between 5 and 7 g . kg-1 body weight support a
      training programme of moderate intensity. Total and saturated fat intakes were
      high at the start of the study (girls: 31.8 +/- 3.5% and 12.2 +/- 2.0% of energy
      intake; boys: 30.3 +/- 4.6% and 12.0 +/- 1.9% of energy intake) and it appeared
      to be difficult to achieve and maintain lower intakes. Consistent low fluid
      intakes around 40 ml . kg-1 body weight were observed. General non-stringent
      advice for improvement of the diet resulted in significant favourable changes
      only for the consumption of wholegrain bread, vegetables, and soft drinks.
      Dietary habits of adolescent sprint athletes are not always according to
      guidelines and are relatively stable but repeated advice can induce moderate
      improvements.

PMID- 21086212
TI  - Injury patterns in young, non-professional dancers.
AB  - The aim of the present study was to assess the prevalence and types of injuries
      in 1336 young, non-professional female dancers (age 8-16 years) who participated
      in a descriptive mixed (cross-sectional/ longitudinal) cohort study. Previous and
      current injuries were diagnosed and later classified into seven major categories.
      Our results show that 569 (42.6%) of the dancers examined manifested an injury.
      Advanced age and increased exposure to dance yielded an equivalent increase in
      the prevalence of injured girls: from 1 of 10 girls in the 8-year-old age cohort
      (mean = 1.05 per 1000 h) to 1 of 3 girls in the 14-year-old age cohort (mean =
      1.25 per 1000 h). Time elapsing between first and second injuries decreased with
      age. Among the youngest group of dancers (8-9 years) the most common injury was
      tendonitis (41%), while in adolescent dancers (14-16 years) knee injuries became
      the leading cause of complaints (33%). We conclude that young, non-professional
      dancers are at high risk of injury. Dancers who had been injured in the past were
      at higher risk for re-injury. Tendonitis in the foot or ankle joint was a common
      injury among the youngest dancers, while knee injuries were common among
      adolescent dancers. A routine screening of this dancer population by an expert in
      dance medicine will reduce the risk for an injury.

PMID- 21086213
TI  - Pivot task increases knee frontal plane loading compared with sidestep and drop
      jump.
AB  - The purpose of this study was to assess kinematic and kinetic differences between
      three tasks (drop-jump, sidestep cutting, and pivot tasks) commonly used to
      evaluate anterior cruciate ligament risk factors. Nineteen female collegiate
      soccer athletes from a Division I institution participated in this study.
      Participants performed a drop-jump task, and two unanticipated tasks, sidestep
      cutting and pivot. Repeated-measures analyses of variance were conducted to
      assess differences in the kinematic and kinetic parameters between tasks. The
      pivot task had lower knee flexion (-41.2 +/- 8.8 degrees ) and a higher valgus
      angle (-7.6 +/- 10.1 degrees ) than the sidestep (-53.9 +/- 9.4 degrees  and -2.9
      +/- 10.0 degrees , respectively) at maximum vertical ground reaction force. The
      pivot task (0.8 +/- 0.3 multiples of body weight) had higher peak posterior
      ground reaction force than the drop-jump (0.3 +/- 0.06 multiples of body weight)
      and sidestep cutting (0.3 +/- 0.1 multiples of body weight), as well as higher
      internal varus moments (0.72 +/- 0.3 N . m/kg . m) than the drop-jump (0.14 +/-
      0.07 N . m/kg . m) and sidestep (0.17 +/- 0.5 N . m/kg . m) at peak stance.
      During the pivot task, the athletes presented a more erect posture and adopted
      strategies that may place higher loads on the knee joint and increase the strain
      on the anterior cruciate ligament.

PMID- 21086214
TI  - Use of dual-task methodology for skill assessment and development: examples from
      rugby league.
AB  - We assessed the attentional demands of drawing and passing in rugby league
      players and investigated the effects of single-task and dual-task training on the
      acquisition, retention, and transfer of skill in these athletes. In Study 1, high
      skilled and lesser-skilled rugby league players performed a standardized 2-on-1
      drill under single-task (primary skill in isolation) and dual-task (primary skill
      while performing a secondary verbal tone recognition task) conditions. No
      differences were detected in primary task performance between groups, although
      the performance of the high-skilled players was more resistant to skill decrement
      under dual-task conditions. In Study 2, high-performance rugby league players
      were randomly allocated to either a single-task or dual-task training group. Each
      group underwent 8 weeks of training between the pre- and post-test sessions.
      While the mean improvement for draw and pass proficiency under dual-task
      conditions in the dual-task training group was greater than in the single-task
      training group (10.0% vs. 2.3%), the differences, while providing a moderate
      effect size (d = 0.57), were not statistically significant. These results suggest
      that the attentional demands of drawing and passing are reduced in high-skilled
      rugby league players compared with their lesser-skilled counterparts. In
      addition, compared with single-task training, dual-task training appears to
      improve the ability to perform dual-task draw and pass tasks (possibly through an
      improvement in time-sharing skills). Further studies are required to verify the
      efficacy of dual-task training as a training stimulus.

PMID- 21086215
TI  - Physical activity recommendations and cardiovascular disease risk factors in
      young Hispanic women.
AB  - Despite the benefits associated with regular physical activity, there is little
      epidemiological evidence to support positive health outcomes when meeting
      physical activity guidelines in high-risk ethnic groups, such as Hispanic women.
      We compared cardiovascular disease risk factors between young Hispanic women who
      meet and those who do not meet current physical activity guidelines. Height,
      weight, waist circumference, and blood pressure were measured in 60 Hispanic
      women aged 20-39 years. Lipids, C-reactive protein, insulin, and glucose were
      assessed. Body composition and cardiovascular fitness were assessed by BodPod and
      maximal oxygen uptake (VO2(max)) respectively. Participants wore an accelerometer
      and average minutes (assessed in 10-min bouts) spent in light, moderate, and hard
      daily activity for weekdays and weekends was determined. Seventy percent of
      participants did not meet the recommended physical activity guidelines, whereas
      30% did so. Following current physical activity guidelines was associated with
      significantly lower mean cholesterol (mean +/- s: 4.2 +/- 0.8 vs. 4.7 +/- 0.9
      mmol . l-1) and triglycerides (0.7 +/- 0.3 vs. 1.1 +/- 0.6 mmol . l-1), and
      higher fat-free mass (43.3 +/- 3.8 vs. 40.2 +/- 5.1 kg) and relative (40.4 +/-
      7.6 vs. 35.6 +/- 7.0 ml . kg-1 . min-1) and absolute (2.5 +/- 0.3 vs. 2.1 +/- 0.4
      litres . min-1) VO2(max) (P < 0.05). These findings suggest an improved health
      status in women who meet versus those who did not meet current physical activity
      guidelines.

PMID- 21086216
TI  - An examination of the relationships among clients' affect regulation, in-session
      emotional processing, the working alliance, and outcome.
AB  - The objectives were to examine the relationships among clients' affect regulation
      capacities, in-session emotional processing, outcome, and the working alliance in
      66 clients who received either cognitive-behavioral therapy or process
      experiential emotion-focused therapy for depression. Clients' initial level of
      affect regulation predicted their level of emotional processing during early and
      working phases of therapy. Clients' peak emotional processing in the working
      phase of therapy mediated the relationship between their initial level of affect
      regulation and their level of affect regulation at the end of therapy; and
      clients' level of affect regulation at the end of therapy mediated the
      relationship between their peak level of emotional processing in the working
      phase of therapy and outcome. Clients' affect regulation at the end of therapy
      predicted outcome independently of the working alliance. The findings suggest
      that clients' level of affect regulation early in therapy has a significant
      impact on the quality of their in-session processing and outcome in short-term
      therapy. Limitations of the study and future directions for research are
      discussed.

PMID- 21086217
TI  - Impaired conditional task performance in a high schizotypy population: relation
      to cognitive deficits.
AB  - Cognitive impairments in schizophrenia have been characterized as reflecting a
      core deficit in the maintenance or use of task-setting cues to mediate
      appropriate ongoing behaviour. This analysis suggests that cognitive deficits in
      schizophrenia will be particularly evident when different task-setting cues
      dictate when different responses are required by the same stimuli. One simple
      task in which task-setting cues are required is a biconditional discrimination.
      Here we examined the performance of participants with high and low schizotypy
      scores (Mason, Claridge, & Jackson, 1995) on a biconditional discrimination and
      an otherwise equivalent, control discrimination that did not require the use of
      task-setting cues. Participants scoring highly on the Introvertive Anhedonia
      subscale (which has been allied to the negative and cognitive symptoms of
      schizophrenia) performed poorly on the biconditional, but not on the control,
      discrimination. No other subscales demonstrated a significant influence on either
      biconditional or control performance.

PMID- 21086218
TI  - Inferring social attributes from different face regions: evidence for holistic
      processing.
AB  - Two experiments investigated the role that different face regions play in a
      variety of social judgements that are commonly made from facial appearance (sex,
      age, distinctiveness, attractiveness, approachability, trustworthiness, and
      intelligence). These judgements lie along a continuum from those with a clear
      physical basis and high consequent accuracy (sex, age) to judgements that can
      achieve a degree of consensus between observers despite having little known
      validity (intelligence, trustworthiness). Results from Experiment 1 indicated
      that the face's internal features (eyes, nose, and mouth) provide information
      that is more useful for social inferences than the external features (hair, face
      shape, ears, and chin), especially when judging traits such as approachability
      and trustworthiness. Experiment 2 investigated how judgement agreement was
      affected when the upper head, eye, nose, or mouth regions were presented in
      isolation or when these regions were obscured. A different pattern of results
      emerged for different characteristics, indicating that different types of facial
      information are used in the various judgements. Moreover, the informativeness of
      a particular region/feature depends on whether it is presented alone or in the
      context of the whole face. These findings provide evidence for the importance of
      holistic processing in making social attributions from facial appearance.

PMID- 21086219
TI  - A practical guide to pediatric multiple sclerosis.
AB  - During the past 10 years much knowledge has been gained about multiple sclerosis
      in the pediatric population. This article summarizes the information relevant to
      the neurologist and pediatric neurologist concerning the diagnosis, differential
      diagnosis and therapy for pediatric MS.

PMID- 21086220
TI  - Melatonin: experience in its use for recording sleep EEG in children and review
      of the literature.
AB  - BACKGROUND: Sleep is known to improve the yield of EEG recording in children but
      is often difficult to obtain. In order to evaluate the efficacy and to test the
      practicability of oral melatonin in obtaining sleep for EEG recording, we studied
      its use in 70 children. RESULTS: Sleep was obtained in 56 children (80%) with a
      mean sleep latency onset of 25 +/- 7.9 min (15-45) after melatonin
      administration, and a mean sleep duration of 17.1 +/- 8.6 min (5-55). 28 children
      (50%) woke up spontaneously after 13.2 +/- 7.9 min (5-40). Among 18 children with
      severe behaviour problems that made interpretable EEG recording in the awake
      state impossible, sleep was obtained in 13 (72%) children. The rare symptoms
      reported (4%) were not reliably related to the use of melatonin. CONCLUSION: The
      study shows a very good efficacy in sleep induction for EEG recording, even in
      children with severe behaviour problems. Sleep duration was, however, short with
      a high proportion of spontaneous arousals but in all patients it was sufficient
      for an initial diagnosis or control of the evolution of epilepsy.

PMID- 21086221
TI  - Heterotopia associated with hippocampal sclerosis: an under-recognized cause of
      early onset epilepsy in children operated on for temporal lobe epilepsy.
AB  - PURPOSE: The aim of this study is to report on 52 children operated on for
      pharmacoresistant temporal lobe epilepsy, with special emphasis on histopathology
      and correlation with clinical features. METHODS: Charts were retrospectively
      analyzed. All children underwent comprehensive clinical, electrophysiological and
      radiological investigations before surgery. Surgical procedures were tailored
      according to scalp, foramen ovale and eventually depth electrode recordings.
      Histopathology was compared with clinical variables (chi (2) and Fisher's exact
      tests). Outcome was evaluated using the Engel scale. RESULTS: Developmental tumor
      was found in 14 cases, malformation of cortical development (MCD) in 26, isolated
      hippocampal sclerosis (HS) in 5 and gliosis in 7. Dual pathology (DP) affected 18
      patients and the main extrahippocampal lesion consisted of microscopic sub
      cortical heterotopias (HS-HT) for 15 patients who shared a particular clinical
      pattern: a history of febrile seizures (FS) and/or brain injury, early onset of
      epilepsy without latent period from FS to the first temporal seizure, and a
      particularly good outcome following surgery. CONCLUSION: In our pediatric
      temporal lobe surgery series, the prevalence for MCD and for DP was higher than
      in adult series. Age at seizure onset depends on pathology, and is earlier when
      involving the neocortex rather than only the hippocampus. We identify the
      association HS-HT (the most frequent DP in this series), with particular clinical
      features.

PMID- 21086222
TI  - Predictors of different types of developmental coordination problems in ADHD: the
      effect of age, gender, ADHD symptom severity and comorbidities.
AB  - It is known that developmental coordination problems in children with ADHD are
      very common. However, it is not clear whether different subtypes of coordination
      problems are associated with ADHD comorbidities, inattentiveness severity, and
      impulsivity/hyperactivity severity. A clinical sample of 122 children and
      adolescents with ADHD and their parents were interviewed. The parents completed
      the validated and reliable Farsi version of DCD-Q regarding their children. The
      internal reliability of the DCD-Q was high for the full scale and the subscales.
      The confirmatory factor analysis indicated that the fit for the hypothesized
      factor structure of the DCD-Q was poor. Linear regression analysis indicated that
      the scores of validated DCD-Q in children with ADHD, except for the fine
      motor/hand writing score, were not predicted by the variables of gender,
      handedness, age, inattentiveness score, hyperactivity/impulsivity score, and
      oppositional defiant behavior score. The fit for the hypothesized factor
      structure of the DCD-Q is poor in children with ADHD. Fine motor/hand writing was
      predicted by inattention severity. The other subtypes of developmental
      coordination problems in children with ADHD cannot be attributed to the variables
      of gender, inattentiveness severity, hyperactivity/impulsivity severity,
      comorbidity with separation anxiety symptoms and oppositional defiant behavior
      score, and handedness.

PMID- 21086223
TI  - Gastric dysmotility following orthopaedic scoliosis surgery in patients with
      cerebral palsy: a case series.
AB  - Scoliosis is a common complication in children with cerebral palsy (CP). In these
      patients, surgical correction carries a high risk of complications. CP is also
      associated with gastrointestinal dysmotility such as delayed gastric emptying and
      gastro-oesophageal reflux. We describe 5 patients with CP in whom symptoms of
      gastric dysmotility clearly exacerbated after orthopaedic scoliosis surgery. They
      all showed persisting vomiting, nausea, bloating, weight loss, and anorexia
      necessitating total parental nutrition and/or jejunal feeding. This intensified
      nutritional support resulted in weight gain. Symptoms, however, persisted in half
      of the patients. The aetiology of these gastro-intestinal motility problems
      following scoliosis surgery remains unclear. Mechanical obstruction needs to be
      ruled out. Delayed gastric emptying may be due to postprandial antral
      hypomotility as a consequence of sympathic stimulation. Malnutrition could
      further aggravate gastrointestinal dysmotility. This complication should be taken
      into account when surgery for spinal deformities in CP patients is planned,
      especially in patients with pre-existing gastrointestinal motility problems.

PMID- 21086224
TI  - Persistence of the stapedial artery associated with facial hemangioma: a case
      report.
AB  - We report on a girl with a left facial hemangioma and absence of the right ear
      and canal who also showed absence of the left vertebral and anterior cerebral
      arteries (ipsilateral to the facial hemangioma), and absence of the external
      carotid artery and presence of stapedial artery on the right side (contralateral
      to the facial hemangioma and ipsilateral to the auditory organ malformation).
      Persistence of the stapedial artery may be related to the facial hemangioma or
      with the hemifacial hypoplasia with similar possibilities. This is the first case
      to the best of our knowledge of the association between P-CIIS and a persistent
      stapedial artery.

PMID- 21086225
TI  - Usefulness of addition of CT perfusion to CT angiography for brain death
      diagnosis in a child.
AB  - CT perfusion is a new technique that is rapid, available and minimally invasive
      which provides functional vascular information and can be made after conventional
      CT and CT angiography at the same imaging session. CT perfusion applications have
      focused on ischemic stroke with only a short series of applications to brain
      death diagnosis. Instead, CT angiography is frequently performed as a
      confirmatory test of brain death, but it has not been completely validated yet.
      Hence CT perfusion may help in supporting the diagnosis of brain death. We
      present the case of a 12-year-old child with clinical criteria for brain death
      who required a confirmatory test. CT angiography and CT perfusion were performed.
      Both revealed the absence of any intracranial blood flow which supported the
      clinical diagnosis of brain death.

PMID- 21086226
TI  - A severe form of non-classic Pompe's disease with normal creatinine kinase level.
AB  - A 24-month-old boy was referred to our pediatric intensive care unit because of
      difficulty in weaning from artificial ventilation. He had 2 bronchopneumonia
      attacks in 2 months; the diagnosis of Pompe's disease was confirmed by low
      glucosidase activity in lymphocytes and cultured fibroblasts without abnormality
      in the serum creatine kinase level. Our patient's creatine kinase levels were
      permanently normal. To the best of our knowledge, our Pompe's case is the first
      in the literature who has normal creatinine kinase levels despite earlier onset
      and rapidly progressive disease.

PMID- 21086227
TI  - Contemporary management of facial soft tissue trauma.

PMID- 21086229
TI  - Lip and perioral trauma.
AB  - The management of perioral injuries is a complex topic that must take into
      consideration the unique anatomy, histology, and function of the lips to best
      restore form and function of the mouth after injury. Basic reconstructive
      principles include three-layered closure for full-thickness lip lacerations.
      Additionally, special care is needed to ensure an aesthetic repair of the
      cosmetically complex and important vermillion border, philtrum, and Cupid's bow.
      Infraorbital and mental nerve blocks provide lip anesthesia for laceration repair
      without distorting crucial aesthetic landmarks. Prophylactic antibiotics are
      usually indicated in perioral injuries due to wound contamination with saliva.
      Perioral burn management is controversial; however, most lip burns can first be
      managed conservatively. Splinting, plasties, and other reconstructive options are
      available after secondary healing of perioral burns. Hypertrophic scars are
      common in the perioral area after trauma. The mainstays of treatment for
      hypertrophic scars on the lips are silicone elastomer sheeting and intralesional
      steroid injections. For large perioral defects, a myriad of reconstructive
      options are available, ranging from primary closure, cross-lip flaps, and local
      tissue transfer, to free tissue transfers such as radial forearm free flaps,
      innervated gracilis free flaps, anterolateral thigh free flaps, and
      osteocutaneous free flaps.

PMID- 21086230
TI  - Management of acute soft tissue injury to the auricle.
AB  - The external ear is commonly involved in facial trauma. Injuries to the ear can
      range from simple lacerations to complete avulsions. We review the normal
      auricular anatomy and vascular supply, as well as the initial management of any
      auricular injury. Furthermore, we review the literature on soft tissue injuries
      of the ear and present a simple algorithm for classifying injuries. The
      classification is based on whether or not cartilage is involved. Injuries to the
      lobule do not involve cartilage and thus are more easily repaired by simple
      closure or Z-plasty. Injuries involving cartilage are further classified into
      partial or complete avulsions. A complete avulsion is then categorized by having
      a wide or narrow pedicle. There is no standardized, definitive management for the
      various types of auricular trauma, and this schema may assist in deciding which
      of the various reconstructive options is most appropriate for a particular case.

PMID- 21086231
TI  - Management of auricular hematoma and the cauliflower ear.
AB  - Acute auricular hematoma is common after blunt trauma to the side of the head. A
      network of vessels provides a rich blood supply to the ear, and the ear cartilage
      receives its nutrients from the overlying perichondrium. Prompt management of
      hematoma includes drainage and prevention of reaccumulation. If left untreated,
      an auricular hematoma can result in complications such as perichondritis,
      infection, and necrosis. Cauliflower ear may result from long-standing loss of
      blood supply to the ear cartilage and formation of neocartilage from disrupted
      perichondrium. Management of cauliflower ear involves excision of deformed
      cartilage and reshaping of the auricle.

PMID- 21086232
TI  - Management of bite wounds in the head and neck.
AB  - An estimated 50% of people in the United States will incur an animal or human
      bite wound at least once in their lifetimes. Although the majority of these
      individuals do not seek medical attention, bite wounds to the head and neck are a
      common reason for emergency department visits. Facial bites are complex injuries
      due to the functional and cosmetic nature of the area, as well as the unique
      polymicrobial infection potential that exists. We present a review of the
      epidemiology and microbiology of bite injuries to the head and neck and provide
      evidence-based recommendations regarding surgical wound closure and antibiotic
      therapy.

PMID- 21086233
TI  - Management of eyelid injuries.
AB  - Injuries to the eyelids mandate a systematic evaluation of the eye and ocular
      adnexa. Anatomic knowledge and an understanding of the etiology of periocular
      injuries are required for evaluation, optimal patient care, and to aid in
      prevention of globe dysfunction. This article also reviews the medical and
      surgical treatments and potential complications of eyelid injuries.

PMID- 21086234
TI  - Management of facial trauma: lessons of war.
AB  - Soft tissue trauma of the head and neck is encountered frequently by the
      battlefield head and neck surgeon. Repair of the soft tissue (as well as bony
      fractures) of the head and neck is undertaken with the intent of providing return
      of form and function to the injured patient. Aggressive management of head and
      neck wounds is necessary to prevent excessive tissue loss due to ischemia or
      infection. Fortunately, the battlefield head and neck surgeon is armed with an
      array of surgical advances including local, regional, and free tissue grafts as
      well as advances in wound care and wound care products to treat the head and neck
      trauma patient. Typical outcome measures after head and neck trauma include
      ability to speak with appropriate articulation, ability to swallow and breathe
      without difficulty, and acceptable facial cosmesis. Advances in timing of repair
      have enabled patients to return to a premorbid condition earlier with improved
      results.

PMID- 21086235
TI  - Fat transfer for the management of soft tissue trauma: the do's and the don'ts.
AB  - Fat transfer for the aging face is an increasingly popular method for facial
      rejuvenation. However, there are inherent risks with fat transfer due to the
      nature of a fat graft that limits its potential use in the context of soft tissue
      trauma. This article reviews these limitations and also describes techniques for
      performing fat transfer to attain safe and long-term aesthetic results in varied
      clinical settings.

PMID- 21086236
TI  - Volume-directed facial soft tissue deficit reconstruction.
AB  - Extensive facial soft tissue volume deficits can pose a significant challenge to
      the facial reconstructive surgeon. These defects are typically the result of
      trauma, tumor extirpation, or congenital defects and produce troubling cosmetic
      and functional morbidities for the patient if the appropriate reconstructive
      paradigm is not embraced. Many options are available, ranging broadly in
      invasiveness, need for donor sites, and longevity of result. Several of these
      options include recent technologies, such as injectable fillers and implantable
      biomaterials, and advances in free flap design and reductions in overall free
      tissue morbidity propel the expanding use of microvascular free tissue transfer.
      With this myriad of options, the surgeon must fully evaluate the extent and depth
      of the soft tissue injury, weigh the advantages and disadvantages of each
      reconstructive option, and finally compose a flexible and graduated
      reconstructive strategy to suit each patient and each defect. A thorough
      knowledge of these techniques is paramount. The purpose of this review is to
      broadly highlight the spectrum of reconstructive options and strategies for
      facial soft tissue volume reconstruction available to the facial reconstructive
      surgeon.

PMID- 21086237
TI  - Parotid gland trauma.
AB  - Parotid trauma can lead to both short and long-term complications such as
      bleeding, infection, facial nerve injury, sialocele, and salivary fistula,
      resulting in pain and disfigurement. Facial injuries inferior to a line extended
      from the tragus to the upper lip should raise concern for parotid injury. These
      injuries can be stratified into three regions as they relate to the masseter
      muscle. Injuries posing the greatest risk of damage to Stensen's duct include
      those anterior to the posterior border of the masseter and necessitate
      exploration. When the duct is disrupted, emphasis should be placed on primary
      repair or re-creation of the papilla; however, proximal ductal lacerations can be
      treated by ligation of the proximal segment. Isolated parenchymal injury can be
      treated with more conservative means. Sialocele and salivary fistula can
      frequently be managed nonoperatively with antibiotics, pressure dressings, and
      serial aspiration. Anticholinergic medications and the injection of botulinum
      toxin represent additional measures before resorting to surgical therapies such
      as tympanic neurectomy or parotidectomy.

PMID- 21086238
TI  - Management of traumatic facial nerve injuries.
AB  - Management of facial nerve injuries requires knowledge and skills that should be
      in every facial plastic surgeon's armamentarium. This article will briefly review
      the anatomy of the facial nerve, discuss the assessment of facial nerve injury,
      and describe the management of facial nerve injury after soft tissue trauma.

PMID- 21086239
TI  - Laser treatment of facial scars.
AB  - Laser treatment of facial scars cannot substitute for optimal initial repair.
      Nonetheless, laser treatments may serve as valuable adjunct interventions after
      initial wound healing. Proper classification of scars into atrophic,
      hypertrophic, and keloid categories enables the appropriate selection of laser
      modality.

PMID- 21086240
TI  - Nasal soft tissue trauma and management.
AB  - The nose is the most prominent of all facial structures and is susceptible to
      many types of trauma. All soft tissue injuries of the nose have the potential to
      distort its appearance and adversely affect the patient's self-image and self
      esteem. Once life-threatening injuries are stabilized, a careful history and
      physical exam should be completed and treatment individualized. The ultimate
      objective of treatment is to achieve both functional and cosmetic restoration
      with timely diagnosis and repair. Immediate nasal reconstruction is ideal when
      medically possible because this decreases long-term sequelae.

PMID- 21086241
TI  - Kinematical and EMG-classifications of a fencing attack.
AB  - 8 expert fencers were studied with a 3-dimensional motion analysis system. Each
      subject performed 10 fleche attacks toward a standardized target. Surface
      electromyography signals (EMG) were recorded of the deltoid pars clavicularis,
      infraspinatus and triceps brachii caput laterale muscles of the weapon arm. The
      recorded EMGs were averaged using EMG wavelet-transformation software. 4 phases
      were defined based on the arm kinematics and used to classify fencers into 2
      groups. A first group of 4 fencers showed an early maximal elbow extension (Early
      MEE) whereas the second group presented a late maximal elbow extension (Late
      MEE). 2 EMG-classifications were based on this kinematical classification, one in
      the time-domain and the other in the frequency-domain by using the spherical
      classification. The time-domain EMG-classification showed a significantly (
      P=0.03) higher normalized deltoid intensity for the Early MEE group (91 +/- 18%)
      than the Late MEE group (36 +/- 13%) in the attack phase. The spherical
      classification revealed that the activity of all the muscles was significantly
      classified (recognition rate 75%, P=0.04) between the 2 groups. This study of EMG
      and kinematics of the weapon upper limb in fencing proposes several
      classifications, which implies a relationship between kinematic strategies,
      muscular activations and fencing success.

PMID- 21086242
TI  - Resistance exercise and lipoproteins in postmenopausal women.
AB  - The specific aims of this study were to quantify the effects of 12 weeks of
      resistance training, as well as a single session of resistance exercise on lipids
      and lipoproteins in obese, postmenopausal women. 21 obese, postmenopausal women,
      not on hormone replacement therapy (age=65.9 +/- 0.5 yr; BMI=32.7 +/- 0.8
      kg/m(2)), were randomly assigned to control (n=12) and exercise (n=9) groups
      matched for age and BMI. For 12 weeks, 3 days/week, the exercise group performed
      10 whole body resistance exercises (3 sets at 8-RM). Fasting (10 h) blood samples
      were collected immediately prior to and 24 h after the first and last exercise
      and control session. Serum was assayed for concentrations of total cholesterol,
      triglycerides, LDL-C, HDL-C, HDL 2-C, HDL 3-C, non-HDL-C and TC:HDL and LDL:HDL
      ratios. The exercise group exhibited a significant (P<0.01) improvement in
      muscular strength, but no change in BMI, body mass or body composition post
      training. Total cholesterol, LDL-C and non-HDL-C were significantly (P<0.05)
      lower in the exercise compared to the control group following the 12 weeks of
      resistance training. Whole body resistance training provides obese,
      postmenopausal women a non-pharmacological approach for the reduction of lipid
      and lipoprotein-cholesterol concentrations.

PMID- 21086243
TI  - Gender-specific oxidative stress parameters.
AB  - The aim of the present study was to examine the association of proteins that
      regulate iron transport/storage content and acute phase response with oxidative
      stress in male and female athletes. Serum ferritin, transferrin, soluble
      transferrin receptor, C-reactive protein, interleukin-6 and oxidative stress
      parameters (reactive oxygen metabolites, superoxide anion, advanced oxidation
      protein products, lipid hydroperoxides, superoxide-dismutase and pro-oxidant
      antioxidant balance) were determined in 138 athletes (73 females and 65 males). A
      general linear model indicated significant gender differences between athletes in
      terms of reactive oxygen metabolites (307.48 +/- 61.02 VS. 276.98 +/- 50.08;
      P=0.030), superoxide-dismutase (114.60 +/- 41.64 VS. 101.42 +/- 38.76; P=0.001),
      lipid hydroperoxides (149.84 +/- 38.95 VS. 101.43 +/- 39.26; P<0.001), pro
      oxidant-antioxidant balance (512.40 +/- 148.67 VS. 413.09 +/- 120.30; P=0.002),
      advanced oxidation protein products (1.49 +/- 0.30 VS. 0.91 +/- 0.25; P<0.001)
      and superoxide (2.61 +/- 0.36 VS. 2.22 +/- 0.35; P=0.001), which were all
      significantly higher in females. Multivariate analysis of covariance indicated
      gender (P<0.001), training experience (P=0.004), C-reactive protein (P=0.002),
      soluble transferrin receptor (P=0.004) and transferrin (P<0.001) as significant
      covariates. Gender accounted for the largest proportion of variability for all
      oxidative stress parameters (46.3%) and female athletes were more susceptible to
      oxidative stress. Iron transport and storage proteins (transferrin and ferritin),
      but also acute phase reactants, were negatively related factors for oxidative
      stress. In conclusion, variation in the ferritin level may contribute to the
      different oxidative stress level between the sexes.

PMID- 21086244
TI  - The thumb during the crimp grip.
AB  - During rock-climbing, fingers grasp holds of various shapes with high force
      intensities. To ideally place the fingertips on the holds, the thumb is sometimes
      positioned on the nail of the index finger. This allows using the thumb as an
      additional actuator by exerting a supplementary force in the same direction as
      the index, middle, ring and little fingers. This study analysed how the forces
      exerted by the fingers are modified by the additional action of the thumb. The
      results showed that the thumb increases the resultant forces exerted on the hold.
      It was shown that the pathology risks of the middle, ring and little fingers were
      not modified in this condition. The finger force sharing was totally re-organized
      due to the support of the thumb. This led to the conclusion that the central
      nervous system organised the association of the 5 fingers. The results were
      discussed in regard to the established theories of the virtual fingers and the
      neutral line of the hand.

PMID- 21086245
TI  - Do clown visits improve psychological and sense of physical well-being of
      hospitalized pediatric patients? A randomized-controlled trial.
AB  - The study tested whether clown visits would be associated with an increase in
      psychological and perceived physical well-being of pediatric patients. Patients
      (6-14 years old) were randomized to a clown visit (n=50) or no-visit control
      (n=50). Patients and parents were administered a modified version of the KINDL-R
      questionnaire at pretest, immediately after the clown visit (posttest), and at a
      4-h follow-up. The experimental group showed an increase in self-reported and
      parent-reported psychological well-being at posttest. However, these effects were
      not maintained at follow-up. There was no effect of the clown visit on perceived
      physical well-being. It is concluded that clown visits appear to improve
      psychological well-being of pediatric patients, but the effects may only be short
      lived.

PMID- 21086246
TI  - Efficacy and acceptability of lanreotide Autogel(r) 120 mg at different dose
      intervals in patients with acromegaly previously treated with octreotide LAR.
AB  - OBJECTIVE: To assess the efficacy of different dosing intervals of lanreotide,
      Somatuline Autogel(r) (Lan-ATG) 120 mg in patients with acromegaly, previously
      treated with octreotide, long-acting release (Oct-LAR). PATIENTS AND STUDY
      DESIGN: Patients previously on Oct-LAR 10, 20, or 30 mg were switched to 6
      repeated deep subcutaneous injections of Lan-ATG 120 mg at intervals of 56, 42,
      or 28 days, respectively. After the third injection, dose intervals were adjusted
      on the basis of insulin-like growth factor 1 (IGF-1) levels. RESULTS: The ITT
      (Intention To Treat) population comprised 35 patients who received at least one
      dose of study medication and at least one post-baseline efficacy assessment.
      Overall, 62.9% (n=22) of patients had normalised IGF-1 levels with Lan-ATG at
      study end (one injection interval after the 6 (th) injection of Lan-ATG), which
      was similar to the proportion at baseline (60.0% [n=21]). QoL did not change from
      baseline to study end. Patient preference for Lan-ATG was highest in the 56-day
      dosing interval group: 71%, 54% and 41% of the patients in the 56, 42 and 28 day
      groups, respectively, expressed a preference for treatment with Lan-ATG
      (preference for Oct-LAR: 29%, 9% and 35%, respectively, while the remainder had
      no preference). CONCLUSION: Lan-ATG 120 mg injected at intervals of 56, 42 and 28
      days provided equivalent hormonal control and QoL to Oct-LAR 10, 20 and 30 mg
      injected every 28 days, respectively. The proportion of patients preferring Lan
      ATG treatment was greater in the longer injection interval groups.

PMID- 21086247
TI  - Relationship between thyrotropin and body mass index in euthyroid subjects.
AB  - BACKGROUND: Several studies have reported that thyrotropin (TSH) levels are
      slightly increased in obese subjects. On the contrary, other studies have
      provided no evidence for an association between thyroid status and body mass
      index (BMI). AIM: Our aim has been to evaluate the relationship between TSH and
      BMI in a group of subjects with obesity, overweight and normal weight with serum
      TSH levels within the reference range, excluding subjects with hypothyroidism and
      hyperthyroidism. SUBJECTS AND METHODS: We evaluated a cohort of 778 euthyroid
      subjects (488 women, mean age 58.5 +/- 15.9 yr) with TSH values between 0.4 and
      5.0 mU/l. There were 321 subjects with obesity (BMI >= 30 kg/m2), 319 with
      overweight (25-29.9 kg/m2) and 138 with normal weight (18.5-24.9 kg/m2). RESULTS:
      Serum TSH levels significantly increased with weight category in studied subjects
      (normal weight, median [interquartile range], 1.24 [0.94-1.72]; overweight, 1.31
      [1.00-1.93]; obesity, 1.66 [1.15-2.44] mU/l; P<0.001). Free thyroxine (T4) was
      not statistically different in subjects within the 3 weight categories. A
      significant correlation was found between TSH and BMI (r=0.217, P<0.001).
      Subjects with serum TSH levels in the upper tertile (1.84-5.0 mU/l) exhibited a
      BMI value (30.8 [26.9-34.9] kg/m2) significantly higher (P<0.001) than that found
      in subjects with TSH levels in the middle (1.13-1.83 mU/l, 28.8 [25.8-32.3]
      kg/m2) or in the lower tertile (0.4-1.12 mU/l, 27.4 [25.4-30.6] kg/m2). There
      were no differences in BMI in patients classified according to tertiles of free
      T4. However, when studying a subgroup of patients with negative thyroid
      autoimmunity (n=375), we could not observe any significant difference in TSH
      levels between obese (n=106, 1.24 [0.90-1.81] mU/l) and non-obese subjects
      (n=269, 1.23 [0.90-1.80] mU/l). No correlation was found between TSH and BMI in
      this subgroup of subjects with negative thyroid autoimmunity (r=-0.035, NS).
      CONCLUSION: These results suggest that the relationship between TSH and BMI
      observed in euthyroid subjects is lost when subjects with negative autoimmunity
      are selected.

PMID- 21086248
TI  - Low free triiodothyronine levels are related to poor prognosis in acute ischemic
      stroke.
AB  - BACKGROUND: Neuroendocrine changes are important processes which accompany
      critical illness, however, the number of clinical studies concentrating on the
      role of thyroid gland hormones in stroke pathogenesis is relatively small. The
      aim of this prospective study was to investigate the relation between free
      triiodothyronine (fT3) levels and the prognosis of patients with stroke. METHODS:
      The prospective study included 387 patients with acute (<24 h of symptoms onset)
      ischemic stroke consecutively admitted to Stroke Units. The subjects with known
      conditions that could interfere with thyroid gland metabolism were excluded. We
      analyzed: the routine blood tests, fT3, free thyroxine (fT4), thyroid-stimulating
      hormone (TSH) levels, unenhanced CT scans, initial clinical status (NIH Stroke
      Scale, NIHSS), 30- and 360- days outcome (modified Rankin Scale-mRS) and
      calculated the survival rate. RESULTS: A higher NIHSS score was in the 1 (st) fT3
      levels tertile, whereas a lower in the 3 (rd) fT3 levels tertile (p=0.006). The
      30- and 360-days mRS scores showed that patients in the lowest fT3 tertile had
      more severe neurological impairment than those in the highest tertile (p=0.001
      and p=0.03, respectively). A 1-year mortality of the patients with the first
      tertile fT3 levels was significantly higher than that of the patients with the
      third tertile hormone levels (p=0.008). Additionally, subjects with fT3 level in
      the lowest tertile demonstrated higher WBC counts and the ventricular system on
      Computed Tomography of head performed on admission to hospital was statistically
      more frequent compressed than that in the patients with fT3 level in the highest
      tertile (p=0.02 and p=0.03, respectively). CONCLUSION: In acute stroke patients
      lower free T3 levels are an important factor related to unfavorable outcome, i.
      e., severe disability and death.

PMID- 21086249
TI  - [Therapeutic options for haemangiomas of infancy].
AB  - The necessity of haemangioma treatment in infants has been controversially
      discussed for years. One reason is the favoured clinical observation of a
      potential spontaneous involution without any therapeutic approach or medical
      treatment, thus avoiding their specific risks. On the other hand, there are
      several reports on serious cases with -rapidly growing haemangiomas including
      severe consequences. There are potential complications such as loss of visus in
      cases of periorbital manifestation. A basic problem is the lack of a unique
      systematic classification, on the basis of which -diagnostic measures,
      therapeutic indications and modes could be compared. Such a classification would
      be much more competent including a sufficient comparison of treatment results.
      The basic aim in management is to achieve control of the haemangioma growth and
      induction of its sub-sequent involution back to only a cosmetic detraction. Each
      threatening functional loss can be classified as an urgent indication for
      treatment. There is a need to consider the treatment options and their values; in
      particular, cryotherapy or laser therapy in localised manifestations are mostly 
      favoured because of the convincing evidence from available data. In the case of a
      more disseminated haemangioma manifestation, the initiation of propranol
      medication is possible, a novel drug for this indication. However, there are no
      follow-up data on the mid-term or long-term outcome available at this time.
      Further studies on the subject are therefore required.

PMID- 21086250
TI  - Endoscopic submucosal dissection assisted by novel "clip fishing method" (with
      video).

PMID- 21086251
TI  - Primary eosinophilic colitis as an unusual cause of chronic diarrhea.

PMID- 21086252
TI  - Intestinal lymphangiectasia presenting with duodeno-jejunal polyposis:
      enteroscopic findings.

PMID- 21086253
TI  - Endoscopic diagnosis of a gastric small cell carcinoma with liver metastasis.

PMID- 21086254
TI  - Desquamative esophagitis due to pemphigus vulgaris.

PMID- 21086255
TI  - Ulcer in Barrett's esophagus probably related to severe kyphosis.

PMID- 21086256
TI  - Diagnostic cholangioscopy with SpyGlass probe through an endoscopic retrograde
      cholangiopancreatography cannula.

PMID- 21086257
TI  - [Hearing impairment - aetiology, diagnostik and auditive rehabilitation].

PMID- 21086258
TI  - Involvement of CYP1A1, GST, 72TP53 polymorphisms in the pathogenesis of thyroid
      nodules.
AB  - Specific genotypes appear to be related to the development of thyroid disease. We
      examined whether polymorphisms of the genes CYP1A1, GSTM1, GSTT1, and TP53 at
      codon 72 are associated with increased risk for thyroid nodules. Blood samples
      were obtained from 122 thyroid patients with nodules and from 134 healthy control
      individuals from Goiania city, GO, Brazil. We found no significant association of
      CYP1A1m1 and CYP1A1m2 genotypes with thyroid diseases (P > 0.05). The null
      genotypes of GSTM1 and GSTT1 genes were predominant in patients with nodules,
      indicating that individuals that possess these genotypes have a predisposition
      for thyroid disease. The genotype p53Arg Arg was associated with a low risk for
      thyroid cancer (OR = 0.15; P < 0.0001), indicating that the arginine allele in
      homozygosis could have a protective effect against carcinogenesis. On the other
      hand, the p53ArgPro genotype was significantly associated with malignant
      neoplastic nodules (OR = 3.65; P = 0.001). Interindividual variation in
      susceptibility to thyroid diseases could provide new perspectives for early
      diagnosis, prognosis and treatment, indicating which patients with thyroid
      nodules will benefit from treatment, depending on specific polymorphic profiles.

PMID- 21086259
TI  - Chromosomal diversity and phylogenetic inferences concerning thrips (Insecta,
      Thysanoptera) in a semi-arid region of Brazil.
AB  - The order Thysanoptera is composed of cosmopolitan phytophagous and predaceous
      insects with diverse life histories, behaviors and habits. This order is
      currently thought to form a trichotomy with Hemiptera and Psocodea; Hemiptera and
      Thysanoptera are considered to be sister groups. The interrelationships within
      Thysanoptera remain unclear and cytotaxonomic studies are scarce in thrips. We
      report, for the first time, chromosomal data on seven species of thrips collected
      from a semi-arid region in the States of Bahia and Pernambuco (Northeast Brazil).
      A distinctive chromosomal pattern was observed in Thysanoptera when compared to
      other members within the infraclass Paraneoptera. Considerable karyotypic
      differences were also found within genera and species of Thysanoptera. Based on
      these data, we suggest that Paraneoptera forms a polyphyletic group and that
      Terebrantia and Tubulifera should be regarded as sister groups. The high
      chromosomal variability observed in Thysanoptera indicates that chromosomal
      rearrangements have played a key role in their speciation pathways.

PMID- 21086261
TI  - Comparison of similarity coefficients used for cluster analysis based on RAPD
      markers in wild olives.
AB  - Five different similarity coefficients (Jaccard, Sorensen-Dice, simple matching,
      Rogers and Tanimoto, and Russel and Rao) were evaluated and 10 wild olives
      analyzed with RAPD markers. The influence of the similarity coefficients on wild
      olives clustering was investigated. Forty-five primers were used on samples from
      10 wild olives (Wild 1 and 2 obtained from Mugla province; Wild 3, 4, 5, 6, 7,
      and 8 from Manisa province and Wild 9 and 10 from Izmir province of Turkey). The
      similarity matrices obtained from RAPD markers were compared by the Mantel test.
      Cluster analysis was made with UPGMA dendrograms, and the consensus fork indexes
      between all pairs of dendrograms were calculated. The Jaccard and Sorensen-Dice
      coefficients gave the same results, due to the fact that both exclude negative co
      occurrences. The dendrograms using the simple matching and Rogers and Tanimoto
      coefficients were similar; Wild 4 (Akhisar, Manisa) and Wild 9 (Bornova, Izmir)
      olives had the closest genetic similarities. This occurred because these
      coefficients include negative co-occurrences. The Russel and Rao coefficients
      produced different results, because they include negative co-occurrences in the
      denominator. We concluded that the coefficients that do not include negative co
      occurrences are more efficient for studies of wild olives clustering based on
      RAPD markers.

PMID- 21086260
TI  - Up-regulation of Id1 in peripheral blood of psoriatic patients.
AB  - Although the precise causes of psoriasis are unclear, it is widely accepted that
      psoriasis is a disorder in which factors in the immune system, enzymes, and other
      biochemical substances that regulate skin cell division are impaired, leading to
      rapid proliferation of keratinocytes and incomplete keratinization. Expression of
      the helix-loop-helix transcription factor Id1 (inhibitor of differentiation/DNA
      binding), functioning as an inhibitor of differentiation, is known to increase in
      psoriatic skin. However, the molecular involvement of this particular biomarker
      in the psoriatic immune system remains to be elucidated. We measured Id1 mRNA
      expression in peripheral blood mononuclear cells (PBMCs) of psoriatic patients
      and healthy controls using semi-quantitative reverse transcriptase-PCR. The
      normalized level of Id1 transcripts in psoriatic patients was about 2-fold higher
      than that in controls (P < 0.05). When we examined the proliferation rate of
      PBMCs, the stimulation index obtained from the phytohemagglutinin stimulation
      assay was not significantly different in psoriatic patients. In patients with
      psoriasis, there was no correlation between the stimulation index and the
      psoriasis area severity index. We suggest that Id1 has a role in causing
      psoriatic immune cell symptoms.

PMID- 21086262
TI  - Genetic differences based on AFLP markers in the mosquito species Anopheles
      darlingi collected in versus near houses in the region of Porto Velho, RO,
      Brazil.
AB  - Anopheles darlingi is the most important malaria vector in Central and South
      America. After a dramatic reduction of malaria cases in the whole Brazilian
      territory, with the lowest abundance being attained by 1970, the disease resurged
      in the Amazon region, where it is now a great public health concern.
      Consequently, better knowledge about vector species became urgent. We examined
      the genetic diversity and population structure of A. darlingi, sampled in four
      localities in the State of Rondonia, Brazil, using 139 amplified fragment length
      polymorphism marker loci. In each locality, samples were collected in two
      environments: a peri-domicile one (in the balconies of houses) and an extra
      domicile environment (about 15 m from the house). Estimates of expected
      heterozygosity, Shannon diversity index and percentage of polymorphic loci showed
      medium to high values, with the samples from the areas closer to Porto Velho
      exhibiting the smallest values. There was evidence of small population
      differences, evaluated by F(st), genetic distance and analysis of molecular
      variance. Comparison between peri- and extra-domicile samples showed greater
      values of F(st) and genetic distance than between pairs of localities, indicating
      influence of environmental conditions on the genetics of populations.

PMID- 21086263
TI  - Nasal cavity ossifying fibrosarcoma: an unusual fibro-osseous neoplasm.
AB  - We describe the case of a 65-year-old woman who presented with left nasal
      obstruction. Clinical and radiographic examinations revealed the presence of a
      soft-tissue mass that had obliterated the left nasal cavity. The mass was
      completely excised via an endoscopic approach. Histopathologic examination
      identified the tumor as an ossifying fibrosarcoma. The patient recovered
      uneventfully and remained free of disease at the 2-year postoperative follow-up.
      To the best of our knowledge, no case of an ossifying fibrosarcoma of the nasal
      cavity has been previously reported in the English-language literature. We
      discuss the features of this case and the clinical presentation, diagnosis, and
      management of fibrosarcomas of the nasal cavity and paranasal sinuses.

PMID- 21086264
TI  - A unique case of multiple sites of pneumatization of the sinonasal bony framework
      in a pediatric patient.
AB  - Anatomic variations of the sinonasal bony framework in the pediatric population
      are quite common. In children with such variations, however, bony pneumatization
      is uncommon. Moreover, pneumatization of the inferior turbinate in children is
      extremely rare; to the best of our knowledge, only 3 cases have been previously
      reported in the literature-none of which involved additional pneumatization
      variations of the sinonasal skeleton. Herein we present a new pediatric case that
      was unique in that an inferior concha bullosa coexisted with rarely seen
      pneumatized anatomic structures.

PMID- 21086265
TI  - Orbital emphysema after a protracted episode of sneezing in a patient with no
      history of trauma or sinus surgery.
AB  - Orbital emphysema is a benign self-limiting condition. It can occur directly (as
      a result of trauma to the face) or indirectly (secondary to a blowout fracture).
      We report a case of orbital emphysema in a 38-year-old man who presented with
      ecchymosis of the right eye, pressure within the right orbit, and periorbital
      swelling following a protracted episode of vigorous sneezing. The diagnosis was
      confirmed by computed tomography. Systemic antibiotics were given, and the
      patient was cautioned to avoid blowing his nose. His signs and symptoms resolved
      within 1 week.

PMID- 21086266
TI  - Submandibular gland hemangioma: clinicopathologic features and a review of the
      literature.
AB  - We conducted a retrospective study to determine the incidence and characteristics
      of submandibular gland hemangioma at our institution. We reviewed the records of
      all patients who had undergone submandibular gland excision from January 1998
      through December 2006. We found a total of 230 such cases. Of these,
      submandibular gland hemangioma was found in 4 patients (1.7%)-3 women and 1 man,
      aged 20 to 47 years (mean 34.8). Their duration of symptoms had ranged from 26 to
      78 months (mean: 49.3). These symptoms had included submandibular swelling, pain
      or discomfort, and features of sialadenitis. Computed tomographic angiography had
      revealed that the hemangiomas were supplied by the facial and lingual arteries.
      Two of the 4 patients had undergone preoperative vascular embolization, but it
      had failed to significantly reduce the amount of intraoperative blood loss. Final
      histopathologic examination had revealed that all 4 lesions were cavernous
      hemangiomas and that they had replaced the normal glandular structure. No
      recurrence was seen during a follow-up that ranged from 47 to 72 months (mean:
      56.3).

PMID- 21086267
TI  - Adenosquamous carcinoma of the lateral oropharyngeal wall.
AB  - Adenosquamous carcinoma of the head and neck is a rare and aggressive tumor, with
      fewer than 100 cases reported in the world literature to date. We report a case
      of adenosquamous carcinoma of the oral pharynx arising as a second primary
      malignancy in a patient being treated for primary gastric MALT (mucosa-associated
      lymphoid tissue) lymphoma. We also review the literature to assess current
      treatment and long-term prognosis of this rare tumor.

PMID- 21086268
TI  - Congenital middle ear cholesteatoma.

PMID- 21086269
TI  - Endoscopic view of a maxillary antrostomy through the inferior turbinate.

PMID- 21086270
TI  - Hypopharyngeal diverticulum formation following anterior discectomy and fusion:
      case series.
AB  - Pharyngoesophageal diverticulum is a rare complication following anterior
      cervical discectomy and fusion (ACDF). Dysphagia is a well-documented
      complication associated with ACDF. It may result postoperatively from a variety
      of etiologies, including hardware displacement, pharyngeal edema, or vocal fold
      paresis. One rare cause of persistent dysphagia is the formation of a
      hypopharyngeal diverticulum, reported in the literature in 9 previous cases. Such
      diverticula after ACDF surgery may have pathogenesis that is distinct from that
      of typical Zenker diverticula. We report 3 new cases of hypopharyngeal
      diverticula in patients who underwent revision ACDFs. Variables assessed included
      age, sex, level of fusion, ACDF-related complications, and diverticulum
      management. Two patients underwent successful open surgical diverticulectomy and
      cricopharyngeal myotomy. In the third case, the patient had a small diverticulum
      close to the surgical hardware and minimal symptoms and was managed
      conservatively. Our cases, combined with the 9 previous cases, demonstrate
      commonalities, particularly with regard to the risk of revision spinal surgery
      and infection and subsequent hypopharyngeal diverticula development.
      Hypopharyngeal diverticulum can occur as a complication of ACDF and should be
      considered in patients with persistent dysphagia after surgery. In this patient
      population, open resection and cricopharyngeal myotomy are recommended.

PMID- 21086271
TI  - Price controls in medical practice.

PMID- 21086272
TI  - Solitary cysticercosis (tapeworm) of the parotid gland.

PMID- 21086274
TI  - Laryngeal candidiasis.

PMID- 21086275
TI  - MALT lymphoma.

PMID- 21086276
TI  - Salivary gland acinic cell carcinoma.

PMID- 21086277
TI  - Differential diagnosis of pediatric tumors of the nasal cavity and paranasal
      sinuses: a 45-year multi-institutional review.
AB  - We conducted a retrospective case-series review to identify the various diagnoses
      of neoplasms of the nasal cavity and paranasal sinuses in a pediatric population.
      Our study group was made up of 54 children-23 boys and 31 girls, aged 8 months to
      16 years (mean: 9 yr). All patients had been diagnosed with a tumor of the nasal
      cavity or paranasal sinuses between Jan. 1, 1955, and Dec. 31, 1999, at one of
      four university-based, tertiary care referral centers. We compiled data on
      tumoral characteristics (location, size, and histopathology), morbidity and
      mortality, and rates of recurrence. Lesions included adnexal neoplasm,
      ameloblastic fibro-odontoma, basal cell carcinoma, benign fibrous histiocytoma,
      blue nevus, chondrosarcoma, compound nevus, epithelioma adenoides cysticum,
      esthesioneuroblastoma, Ewing sarcoma, fibrosarcoma, giant cell granuloma,
      granulocytic sarcoma, hemangioma, hemangiopericytoma, Langerhans cell
      histiocytosis, lymphangioma, lymphoma, melanoma, neuroblastoma, neurofibroma,
      ossifying osteofibroma, osteochondroma, osteosarcoma, port wine stain,
      rhabdomyosarcoma, Spitz nevus, and xanthogranuloma. To the best of our knowledge,
      this is the largest such study of its kind to date. We believe that the large
      size of this study and the data on disease incidence will allow clinicians to be
      better informed of the differential diagnosis of neoplasms of the nasal cavity
      and paranasal sinuses in the pediatric population.

PMID- 21086278
TI  - Microdebrider-assisted versus laser-assisted turbinate reduction: comparison of
      improvement in nasal airway according to type of turbinate hypertrophy.
AB  - A case-control study was conducted at our secondary referral hospital to compare
      the efficacy of microdebrider-assisted turbinate reduction (MATR) with laser
      assisted turbinate reduction (LATR) and to evaluate their efficacy according to
      types of hypertrophic inferior turbinates. All patients who underwent only
      inferior turbinate surgery for refractory nasal obstruction were included. The
      required minimum follow-up period was 3 months postoperatively. Thirty-seven
      patients were enrolled in this study-22 in the MATR group and 15 in the LATR
      group. The patients were subclassified into mucosal (n = 14) and bone (n = 23)
      hypertrophy groups. Subjective (visual analogue scale) and objective (endoscopic
      score) assessments were performed prior to surgery and 3 months after surgery.
      Generally, the visual analogue scale and endoscopic score were significantly
      improved after surgery, in both the MATR and the LATR groups. In the MATR group,
      the visual analogue scale and endoscopic score improved regardless of type of
      hypertrophy. However, in the LATR group, these measurements improved only in
      cases with mucosal hypertrophy. We conclude that both MATR and LATR are good
      surgical techniques in patients with chronic hypertrophic inferior turbinates who
      have substantial nasal obstruction. However, MATR is superior to LATR, especially
      in cases with bone hypertrophy.

PMID- 21086279
TI  - Effects of chlorhexidine/benzydamine mouth spray on pain and quality of life in
      acute viral pharyngitis: a prospective, randomized, double-blind, placebo
      controlled, multicenter study.
AB  - We conducted a prospective, randomized, double-blind, placebo-controlled,
      multicenter study to assess the efficacy of chlorhexidine gluconate/benzydamine
      HCl mouth spray for reducing pain and improving quality of life in patients with
      acute viral pharyngitis. Prior to treatment, patients rated the intensity of
      their pain on a visual analog scale and evaluated their quality of life on the 36
      Item Short-Form Health Survey. Patients were then randomized to receive either
      paracetamol (acetaminophen) plus chlorhexidine/benzydamine or paracetamol plus
      placebo for 7 days. On days 3 and 7 of treatment, the participants again rated
      the intensity of their pain, and on day 7, they again rated their quality of
      life. A total of 164 patients were evaluable at study's end-80 in the
      chlorhexidine/benzydamine group and 84 in the control group. A comparison of self
      evaluations revealed that the active treatment group reported less pain on both
      day 3 (p < 0.001) and day 7 (p = 0.002). Likewise, the chlorhexidine/benzydamine
      group reported a significantly better quality of life on day 7 (p < 0.001).
      Chlorhexidine/benzydamine was well tolerated, and no serious adverse events were
      observed.

PMID- 21086280
TI  - Laryngeal paraganglioma: report of an unusual entity.
AB  - Paragangliomas are rare in the larynx. When they do occur there, the most common
      subsite is the supraglottic compartment. Unlike other neuroendocrine tumors of
      the larynx, laryngeal paragangliomas are three times as common in women as in
      men. Although a preoperative biopsy is often performed to establish the
      diagnosis, this procedure carries a considerable risk of bleeding, which may
      necessitate a tracheotomy to secure the airway. Immunohistochemical staining is
      useful in the differential diagnosis to distinguish a paraganglioma from other
      neuroendocrine tumors. Computed tomography and/or magnetic resonance imaging with
      preoperative angiography and possible embolization are important to obtain prior
      to treatment. Surgical excision is the treatment of choice.

PMID- 21086282
TI  - [Painful ejaculation: a review].
AB  - Pain at ejaculation/orgasm perceived in perineum, urethra and/or urethral meatus,
      has a profound impact on the quality of life of the affected man. Although
      underestimated, this condition is reported to have a 1-9.7% prevalence over the
      general population. METHODS. Structured review of the relevant available
      literature. RESULTS. Among the main causes of pain experienced at
      ejaculation/orgasm are: prostatevesicular causes (LUTS/BPH, prostatitis,
      ejaculatory duct obstruction, vesicular stone), postsurgical causes (radical
      prostatectomy, inguinal hernioplasty), pharmacologic causes (antidepressants),
      psychogenic causes (psychosexual conflicts, sexual abuse), rare causes. For these
      pathologies, diagnostic and therapeutic strategies have been proposed.
      CONCLUSIONS. Ejaculatory pain is associated with a high level of personal
      distress, and represents a possible request for help within the
      andrologic/urologic area. Each field specialist should be competent in correctly
      interpreting every single case, in order to manage it appropriately.

PMID- 21086281
TI  - [State of the art and controversies in the treatment of testis germ-cell tumors
      (TGT)].
AB  - Many different, intersecting strategies are available for managing germ-cell
      cancers,particularly in early-stage disease. Which is 'right' remains a matter of
      debate, and requires balancing efficacy against late effects, bearing in mind the
      complexity of treatment strategies and the available expertise.
      </font></font></i>

PMID- 21086283
TI  - [Small volume (<0.5 cc) prostate cancer: characteristics and clinical
      implications].
AB  - INTRODUCTION. It is not well known how many Small Volume Prostate Cancers (SVPC)
      may host high grade (Gleason pattern 4/5) or have extraprostatic extension in
      particular in the national setting. Features of SVPC are very interesting since
      they raise controversies in diagnosis and have important clinical implications in
      treatment strategies. The diagnosis may be difficult and the treatment ranges
      from active surveillance to radical surgery. AIM. We evaluate clinical and
      pathological features of SVPC in surgical specimens of patients who underwent
      biopsy and radical prostatectomy. METHODS. We analysed a consecutive series of
      849 radical prostatectomies performed between 2005 and 2008. Inclusion criteria
      were: biopsy specimen available, pathological tumor volume analysis according to
      standard criteria, whole-mount section 3 mm step analysis according to Stanford
      protocol, clinical parameters (PSA, DRE, number of core biopsy taken). EXCLUSION
      CRITERIA: any hormonal manipulation before surgery and cT1A/B stage. Data were
      analysed using SPSS for statistical comparison. RESULTS. 238 patients were
      evaluated. SVPC<0.5 cc was observed in 58 (24.3%). Overall in 17/58 (29.3%) a
      clinical/pathological relevant disease was observed. In 16/58 (27.5%)
      pathological Gleason Score (GS) was 7-8, in 5/58 (9%) pathological stage was T3.
      The number of tumor foci was >1 in 78.3%, tumor-involving in both lobes in 55%.
      Unifocal disease was observed in 22%. Clinically relevant disease is
      significantly associated with total cancer volume (0.20 versus 0.31, p 0.007),
      but not to tumor foci (2.5 versus 2.0). PSA, age, no. of positive cores, DRE were
      not predictive of clinical relevant disease. Six of 17 (35%) cases with SVPC -
      who were in the low risk category (PSA <10, biopsy Gleason score <7 and negative
      DRE), had clinical relevant disease. CONCLUSION. SVPC are clinically relevant in
      29.3% since they have a Gleason pattern 4 (27.5%) or have only pathological T3
      (9%). Early diagnosis techniques and treatments have to consider that SVPC
      prostate cancer may contain high risk disease in 1/4 of cases. Clinical
      parameters are not useful to accurately detect high risk SVPC.

PMID- 21086285
TI  - Early clinical experience with different mesh in correction of high-degree
      cystocele.

PMID- 21086284
TI  - [4 hands/4 ports laparoscopic radical prostatectomy].

PMID- 21086286
TI  - Reducing pain during transperineal prostatic biopsy.

PMID- 21086287
TI  - Complete duplication of bladder, urethra, clitoris and vagina associated with
      bilateral ureteral reflux in an old female patient: unique case.

PMID- 21086288
TI  - [Investigational drug therapies for overactive bladder syndrome: the potential
      alternatives to anticolinergics].

PMID- 21086289
TI  - [Second-line intravesical gemcitabine in high risk superficial bladder cancer:
      our experience].

PMID- 21086290
TI  - [The activities of Risk Management].

PMID- 21086291
TI  - [Combined endoscopic and surgical technique for the repair of posterior traumatic
      urethral stricture].

PMID- 21086292
TI  - X-ray diffraction study on human male reproductive tract and semen.

PMID- 21086293
TI  - [Sexual activity and urinary incontinence in women].

PMID- 21086294
TI  - Radical cystectomy for transitional cell carcinoma with orthotopic neobladder in
      renal transplant recipients: surgical procedure, functional and therapeutic
      evaluation.

PMID- 21086295
TI  - A rare case of hematuria from colonic adenocarcinoma spreading to the bladder via
      the stented ureter.

PMID- 21086296
TI  - [Positioning of a malleable penile prosthesis. Solving an intraoperative
      complication].

PMID- 21086297
TI  - [Integrated treatment with hyperthermia and chemotherapy for non-muscle invasive
      bladder cancer].
AB  - Oncology-applied hyperthermia is a very old form of therapy. In recent years
      hyperthermia has been investigated with the aim of improving the treatment for
      non-muscle invasive bladder cancer to prevent relapse and disease progression, in
      association with mitomycin-C, a well-known chemotherapeutic agent, to enhance its
      effect. Target patients are those with non-muscle invasive transitional cell
      carcinoma, showing medium (Ta-T1, G1-2, multifocal, diameter >3 cm) or high (T1,
      G3, multifocal or rapidly relapsing, CIS) risk for recurrence or progression. The
      treatment may be prophylactic following tumor eradication, or ablative when tumor
      cannot be otherwise eradicated. Several studies have shown the benefits of
      thermochemotherapy with lower risk for relapse than other treatment options, and
      66-80% complete responses following ablative treatment. This association of
      treatments has a synergic therapeutic effect, higher than administering
      hyperthermia and drug therapy as single treatment.

PMID- 21086298
TI  - Synchronous urinary tract metastases from breast cancer.
AB  - Breast carcinoma has a metastatic potential to any organ system. However, breast
      carcinoma metastases to the urinary tract have very rarely been described. The
      authors present the case of a patient with a synchronous right ureteral and
      vesical metastasis of a breast cancer. This is the unique case reported in
      Literature of synchronous urinary metastatic localization from breast invasive
      lobular carcinoma.

PMID- 21086299
TI  - [Role of the vesico-urethral anastomosis biopsy in the diagnosis of local
      recurrence following radical prostatectomy.Our experience].
AB  - In the long-term there is biochemical evidence of recurrent prostate carcinoma in
      approximately 40% of patients after radical prostatectomy (RP). Detecting the
      site of recurrence (local vs distant) is critical for defining the optimum
      treatment. Pathological and clinical variables (Gleason score, involvement of
      seminal vesicles or lymph nodes, margin status at surgery, and especially the
      timing and pattern of PSA recurrence) may help to predict the site of relapse.
      Transrectal ultrasonography (TRUS) of the prostatic fossa in association with
      TRUS-guided needle biopsy is considered more sensitive than a digital rectal
      examination for detecting local recurrence, especially if PSA levels are low.
      Although it cannot detect minimal tumor mass at very low PSA levels (<1 ng/mL),
      TRUS biopsy is presently the most sensitive method for detecting local
      recurrence. Nevertheless, the conclusive role of biopsy of the vesico-urethral
      anastomosis remains unclear. However, [11C]-choline tomography (which is better
      than conventional imaging for detecting metastatic tumor) has low detection rates
      for local disease and is considered complementary to TRUS in this setting.
      Patients with a high PSA after RP may be managed with external beam salvage
      radiotherapy. An initial PSA of <1 ng/mL, Gleason score < 8 and radiation dose of
      66-70 Gy seem to be key factors in determining success. Although a positive TRUS
      anastomotic biopsy may predict a better outcome after radiation therapy, the need
      of taking a biopsy in the event of PSA failure remains under investigation. The
      value of salvage radiation to the prostatic bed for PSA-only progression after RP
      remains in question.

PMID- 21086300
TI  - [Prostate cancer: transrectal high-intensity focused ultrasound for the treatment
      of local recurrence after radical prostatectomy or radiotherapy].
AB  - OBJECTIVES. To evaluate the efficacy and safety of transrectal high-intensity
      focused ultrasound (HIFU) as salvage therapy for locally recurrent prostate
      cancer after external beam radiotherapy or recurrences located in the region of
      vesicourethral anastomosis after radical prostatectomy. METHODS. Transrectal
      biopsy of the prostate (recurrence after radiotherapy) or in the region of
      vesicourethral anastomosis (recurrence after prostatectomy) was performed in all
      cases at the time of biochemical relapse. Only patients with positive biopsy were
      treated. Systemic disease was excluded by PET-CT and bone scan. All treatments
      were carried out under spinal anesthesia. The device used was Ablatherm (EDAP,
      Lion, France). The patients were followed with PSA measurement every 3 months and
      clinical examination every 6 months. In case of biochemical relapse we performed
      re-biopsy. RESULTS. From 2002 to 2008 we treated 19 patients with local
      recurrence after radiotherapy. The mean follow-up was 30 months for each patient
      (range 6-72 months). 9 patients (47%) are disease-free at last followup, with PSA
      < 1 ng/mL. 9 patients experienced biochemical failure: 8 were treated with
      androgen deprivation, 1 with salvage prostatectomy. 2 patients died of the
      disease. Adverse events related to HIFU included 1 rectourethral fistula
      (observed before the use of specific parameters dedicated to this patient
      population) and mild incontinence (2-3 pads/die) in 4 patients. From 2002 to 2008
      we treated 27 patients with a local recurrence after radical prostatectomy. Mean
      pre-HIFU PSA was 2.17 ng/mL (range 0.5-8 ng/ml); the Gleason score ranged from 5
      to 8. All patients reached a minimum follow-up of 20 months (range 20-80 months).
      Median PSA nadir was 0.2 ng/ml. The disease-free rate was 51% (14/27); these
      patients have a median PSA of 0.2 ng/ml at last follow-up. 81% (22/27) of control
      biopsies were negative. There were no intra-operative or post-operative
      complications. CONCLUSIONS. The small number of patients in our series limits our
      ability to draw any definitive conclusions. We believe that HIFU may be a
      potentially useful treatment option for patients who develop prostate cancer
      recurrence after external beam radiotherapy or in the region of vesicourethral
      anastomosis after radical prostatectomy. The procedure is safe, side effects are
      acceptable and do not add significant morbidity to the previous radical
      treatment. HIFU lesions are targeted only to the area of recurrence. It is
      important to remember that, in case of failure, the patient can undertake any
      other therapies.

PMID- 21086301
TI  - [Anterior urethral therapy].
AB  - Surgical treatment of anterior urethral stenosis encompasses a large number of
      techniques. In literature there are few prospective studies that could compare
      the efficacy of different techniques. Most of these studies are retrospective and
      not multicentric. We present a review of the literature on the treatment of
      penile and bulbar strictures, focusing the attention on different kinds and
      numbers of complication, and showing shortand long-term results of each
      technique.

PMID- 21086302
TI  - [Early vs delayed radical cystectomy compared in highgrade superficial bladder
      tumors].
AB  - Objectives. The treatment of aggressive superficial TCC of the bladder remains
      controversial. In fact, although still classified as 'superficial', it has been
      shown that the biological characteristics of T1G3 bladder tumors are the same as
      those of the muscle-invasive group (T2 and above). Even with close monitoring and
      intensive intravesical therapy, the reported risk of muscle invasion in these
      patients is 53% and 1/3 die from this disease in the long-term. The aim of this
      study is to determine whether the timing of radical cystectomy affects the
      survival of patients with aggressive superficial bladder tumor. Methods. We
      consider 74 patients who underwent radical cystectomy between November 1994 and
      October 2006 before a diagnosis of T1G3 bladder tumor. These patients were
      divided in 2 subgroups: group A (n=27, 25 M and 2 F) who underwent immediate
      radical cystectomy, and group B (n=47, 40 M and 7 F) who underwent other
      conservative treatments before radical cystectomy. Results. The two subgroups
      were similar concerning age (66.29+/-8.37 yrs vs 66.87+/-8.6 yrs, respectively, p
      NS) and the timing of follow-up (respectively 77+/-45 vs 60+/-35 mths, p NS).
      Moreover, the progression-free survival was significantly higher in subgroup A
      (53.73+/-48.54 vs 31.94+/-35.19 mths, log-rank p<0.05) as well as the overall
      survival (59.73+/-45.37 vs 36.45+/-33.96 mths respectively, log-rank p<0.05).
      Comparing the histological examinations, the two subgroups were significantly
      different concerning the T stage (superficial tumors 14/27 vs 16/47,
      respectively, p<0.05; invasive tumors 13/27 vs 31/47, respectively, p<0.00005)
      and the lymphonodal dissemination (2N+/27 vs 11N+/47, respectively, p<0.0005). .
      Delaying radical cystectomy for aggressive superficial bladder tumors leads to a
      worse progression-free survival; the overall survival is likely to be due also to
      an early lymphonodal dissemination, which occurs extending the timing between
      diagnosis and radical treatment.

PMID- 21086303
TI  - [Robot-asssisted laparoscopic radical prostatectomy (ralp). Oncological and
      functional findings after 90 cases].
AB  - The RALP is the most modern technology available for the treatment of
      intracapsular prostate cancer (CaP), which can produce a shorter learning curve
      and better results than the traditional techniques. METHODS. Between March 2005
      and March 2008, 90 patients (64.3 ys, range 52-71) with intracapsular CaP
      underwent RALP at our institute. Before surgery the patients underwent routine
      examinations and filled in IIEF, IPSS and EORTC-QLQC30/PR 25 questionnaires.
      Patients were followed up with PSA assay, physical examination and compilation of
      the questionnaires. Median follow-up was 12.5 months (range 1-35 months).
      RESULTS. Mean operative time was 230 min. Discharge and catheter removal were at
      day 7.4 and 8.2, respectively, after surgery. Pathological staging reported pT2
      and pT3 in 57 (63%) and 33 patients (37%), respectively. Positive surgical
      margins were assessed in 30 patients (33%), particularly 8.7% in pT2 tumors. The
      one-year biochemical disease-free survival rate was 90%. Regarding the functional
      results, 81 patients (90%) were perfectly continent while a mild and a moderate
      incontinence were reported in 7 (8%) and 2 (2%) patients, respectively. Mean IPSS
      score decreased from 8 to 4; among the patients who underwent bilateral nerve
      sparing RALP and no adjuvant therapy, 31 (70.4%) reported satisfactory sexual
      intercourses. Concerning postoperative quality of life, mean EORTC-QLQC30/PR 25
      questionnaires scores were very similar before and after RALP. CONCLUSIONS. After
      90 cases of RALP the oncological and functional results are definitely promising.
      However, a wider number of patients and a greater follow-up are needed to confirm
      these data particularly as regards the functional results.

PMID- 21086304
TI  - [Bladder augmentation and urinary diversions in kidney transplants].
AB  - There is some controversy about the safety of kidney transplant in patients with
      augmented or diverted urinary system: they are considered higher risk recipients
      in view of increased technical problems and infective complications leading to
      pyelonephritis and graft loss. The ureter of a transplanted kidney should be
      anastomosed into a reservoir with an adequate capacity, with low bladder
      pressure, with good compliance, and efficient voluntary empting. Ileal and
      sigmoid bladder augmentation, usually associated with clean intermittent
      catheterization, has become a well-accepted part of the urological practice and
      has been used for implantation of the transplant ureter. During the last years,
      the interest in new biomaterials for reconstructive surgery has increased.
      Experimental studies showed how these requests can be satisfied by porcine small
      intestinal submucosa SIS (StratasisTM): this can be degraded by the host and
      substituted by "new tissue". In four recent cases we have used SIS to obtain an
      augmented, normalpressure and good compliance bladder reservoir, with three
      (epithelial, muscular and adventitial) layers normally represented.

PMID- 21086305
TI  - [Penile prosthesis implantation in kidney-transplanted patients].
AB  - Most kidney transplantations are performed on middle-aged men for whom problems
      of sexual potency are still of great importance. Although a functional renal
      graft improves the problem in some patients and others resolve with oral or
      intracavernous therapy, about 20% of patients do not have a good response. In non
      responders, tricomponent penile prosthesis implantation is possible. In the last
      10 years we have implanted with no complications 7 tricomponent AMS 700
      prostheses in patients not otherwise responding. Our good results confirm that
      patients with kidney transplantation should be considered good candidates to the
      penile prosthesis if the erectile dysfunction persists after different therapies.

PMID- 21086306
TI  - [Is prophyilaxis necessary after urodynamic tests? Our experience].
AB  - Urodynamic studies should be performed only on patients with sterile urine. The
      use of prophylaxis after urodynamic investigation is debated (positive
      urinoculture in 9 to 15% of cases). The Units of Urodynamics at the Urological
      Clinic of the University of Genoa and of the Galliera Hospital of Genoa assessed
      the prevalence of bacteriuria on a sample of 336 patients (314 females and 22
      males), average age 62.3, between January and December 2006. All patients with
      sterile urine before examination underwent a complete urodynamic test.
      Concomitant diseases were: diabetes (7.7%), multiple sclerosis (3.5%),
      Parkinson's disease (1.2%), urinary retention treated by autocatheterism (1.2 %).
      Urinoculture was performed seven days after the urodynamic study. All patients
      were asymptomatic; 40/336 urinocultures were positive (E. coli 80%, Proteus M.
      10%, other 10%). The prophylaxis does not eliminate but only reduces post
      urodynamic infections; we believe that the cost-benefit ratio is unfavorable.

PMID- 21086308
TI  - ["ReMeEx", the adjustable-tension suburetral sling in the treatment of stress
      urinary incontinence due to intrinsic sphincteric dysfunction (type III)].
AB  - The anti-incontinence methods "tension free" may be insufficient in the treatment
      of stress urinary incontinence (IUS) due to intrinsic sphincteric dysfunction
      (ISD). We report our findings on the use of the suburetral sling with adjustable
      tension "Remeex" sistem in the treatment of 24 patients. METHODS. Between May
      2002 and February 2008, 24 patients with IUS of type III, were subjected to
      suburetral sling "Reemex." Positioning. The intervention provides a vaginal
      access to the positioning of suburetral sling and an access to the positioning of
      a varitensor which the wires are connected at the sling seats, recovered by the
      passage of a Stamey needle carrier of. The average operative time was
      approximately 70 minutes, the resignation was in I-II day. The tension of the
      sling was adjusted the day following intervention by turning the screw connected
      to the varitensor. Patients were followed with physical examination and completed
      the Korman's questionnaire about the quality of life. RESULTS. At a follow-up
      average 30 months, 21 patients (87.5%) were perfectly continent with improvement
      of quality of life. Among the complications, wound infection occurred in 2
      patients (8%); 1 (4%) with mild recurrence IUS; 1 (4%) reported "de novo"
      urgency, 1 (4%) reported urinary retention. CONCLUSIONS. Our data show that the
      use of the suburetral sling "ReMeEx" is a effective option in the treatment of
      IUS due to ISD which is a condition often secondary to urogynecologic surgery and
      refractory to common techniques antincontinence.

PMID- 21086309
TI  - [Using computed tomography to predict in vivo stone chemical composition].
AB  - OBJECTIVES. Several authors hypothesized the usefulness of the non-contrast
      helical computed tomography (NCHCT) with the determination of stone Hounsfield
      Unit (HU) values in order to predict urinary stone compositions. Preoperative
      knowledge of stone composition might be interesting in pre-operative decision
      making process. The aim of this study was to evaluate the possible correlation
      between stone chemical composition and correspondent stone HU value in an in-vivo
      experience. METHODS. Forty patients with urinary stones were preoperatively
      studied with abdominal NCHCT, where stone HU values were reported. Stone chemical
      composition was obtained in each patient, using the colorimetric method. The HU
      value of each stone was compared with the correspondent chemical analysis.
      Results. The median HU values of calcium oxalate (n=10), mixed calcium oxalate
      and phosphate (n=19), calcium phosphate (n=2), uric acid (n=6) and mixed uric
      acid and calcium oxalate (n=3) stones were 1060 HU [interquartile range (IQR)
      743.75-1222.5]; 900 HU (IQR 588.5-1108.5); 774 HU (range 720-828); 371 HU (IQR
      361.25-436.25) and 532 HU (range 476-626), respectively. CONCLUSIONS. Our results
      confirmed a statistically significant difference of the HU values between calcium
      and pure uric acid calculi, suggesting a correlation between stone chemical
      composition and CT-density. Hounsfield unit.

PMID- 21086307
TI  - [Vesical sequelae of transverse myelitis. Long-term urodynamics observations in
      adult patients].
AB  - Transverse myelitis is a rare autoimmune inflammatory disease often secondary to
      viral infection of the spinal cord; it frequently has vesico-sphynteric
      complications. Between January 2000 and December 2005 we performed urodynamic
      examination on 13 consecutive patients (7 females and 6 males) with previous
      diagnosis of transverse myelitis. Mean age was 54.5 years; transverse myelitis
      had been diagnosed a mean of 6.3 years earlier; etiology of myelitis was viral
      infection in 5 cases, autoimmune in 3 cases, insect bite in 1 case, unknown in 4
      cases. The neurological sequelae included paraparesis in 3 cases and tetraparesis
      in 2 cases. SYMPTOMS: dysuria 46%, slow stream 15%, pollakiuria 23%, urgency 30%;
      urge incontinence 38%, stress incontinence 15%. 3 patients performed 4 clean
      intermittent catheterisms (CIC), 2 patients 2 CICs. Eight patients had maximum
      cystometric capacity above 350 mL, the others had a mean capacity of 223 mL. Four
      patients showed no bladder sensitivity. Voluntary micturitional reflex was
      observed in 4 patients. Detrusor overactivity was diagnosed in 9 patients, 10
      patients had mean residual post-micturition (RPM) of 218 mL, 2 patients showed
      detrusor-sphincter dyssynergia, 2 patients were found to be obstructed at
      pressure-flow study. Urodynamic follow-up is indicated in these patients with or
      without neurological complications (possibility of detrusor overactivity, urinary
      retention, detrusor-sphincter dyssynergia); the follow-up personalizes the
      diagnosis and therapy, and prevents complications.

PMID- 21086310
TI  - [Solitary fibrous tumor of the kidney. A propos of a case].
AB  - Solitary Fibrous Tumors (SFT) are rare spindle cell neoplasm that typically
      originate from the pleura. However, cases of the SFT are described with origin in
      other organs, including the urinary and genital apparatus. Within the kidney,
      except from the renal pelvis, only 19 cases of SFT are described and such rarity
      of localization makes the histogenesis and the prognosis of the tumor rather
      unknown. We report the case of a 72-year-old lady who attended our Unit for a
      mass that was clinically palpable at the level of the left hemiabdomen. The
      tomodensitographic test indicated a 19cm-diameter mass of likely pertinence of
      the middle bystender of the left kidney. She had undergone left radical
      nephrectomy. The histological examination highlighted a solitary fibrous tumor
      (SFT): the presence of hypercellularity, of cellular pleiomorphism and of a high
      number of mitosis has led to a histological diagnosis of malignancy for the
      neoplasm analyzed. The SFT are of rare clinical comparison: this does not allow
      for a deep knowledge of the lesion histogenesis and prognosis; moreover, the
      clinical behavior should be more precisely defined.

PMID- 21086311
TI  - [Disease progression in bladder cancer: which developments since 1994].
AB  - Objectives The introduction of PSA in clinical practice has resulted in
      decreasing the death rate form prostate cancer and in a downward shift of the
      pathological stage in radical prostatectomy specimens. This seems not to be the
      case for bladder cancer. In order to verify this assumption, we have reviewed the
      charts of the patients operated on of radical prostatectomy and radical
      cystectomy between 1994 and 2006. METHODS 456 and 491 consecutive patients,
      respectively, underwent radical cystectomy and radical prostatectomy with
      bilateral lymph nodes dissection. We excluded all the patients who had received
      neoadjuvant treatment or did not undergo node dissection. The patients were
      divided into two consecutive groups according to the year of treatment: group 1
      included pts treated from 1994 to 2000, and group 2 pts from 2001 to 2006. The
      histopathological findings of the two groups of pts were compared. The difference
      among TNM systems has been balanced evaluating histopathological reports
      critically and converting them to the 2002 edition. RESULTS. For patients with
      prostate cancer, those in group 2 had a decrease in the incidence of
      extracapsular extension and lymph nodes invasion. The bladder cancer patients
      belonging to group 2 had a greater number of T2, but there was an increased
      number of pN+ in this group. CONCLUSIONS Even if there is a decline in locally
      advanced disease in patients with bladder cancer, our retrospective analysis did
      not show a comparable success in early diagnosis as it did for prostate cancer.
      There is undoubtedly an increase in the lymph node dissemination, whether this is
      due to a more extended lymph node dissection or to a premature dissemination
      remains questionable. Public awareness regarding bladder cancer and its risk
      factors is limited, but several studies have reported that a delay in diagnosis
      of invasive bladder cancer is an adverse prognostic factor. A higher care in the
      development of new diagnostic markers for bladder tumors and especially in the
      screening protocols together with an earlier radical therapy could hopefully
      improve the management of such a pathology, as it happened for prostate cancer.

PMID- 21086312
TI  - [Conservation of erectile function following brachytherapy for low-risk prostate
      cancer].
AB  - Brachytherapy (BT) is an effective option to treat low-risk prostate cancer
      (CaP). While oncological results are consistent with those reported following
      radical retropubic prostatectomy (RRP), attention may be given to the advantages
      in terms of functional results that a less invasive approach can ensure. The aim
      of this study is to assess the impact of the conservation of erectile function
      (EF) in patients who underwent BT with a short and medium term follow-up.
      MATERIALS AND METHODS. Between May 1999 and January 2005, 170 patients underwent
      BT for low-risk CaP (intracapsular prostate cancer, PSA , 10 ng/mL, Gleason score
      , 6). Among them, 58 patients (average age 65.6) with good preoperative erectile
      function (IIEF>22) and a minimum follow-up of 5 years were selected. The results
      were evaluated by comparing the values of pre- and postoperative IIEF
      questionnaire at 3 months, 1 and 5 years of medium follow-up. RESULTS. At a mean
      3-month follow-up, a spontaneous recovery of EF (IIEF> 17), strongly influenced
      by urinary irritative disorders, was reported by 34/58 patients (58%). At 1 and 5
      years, good EF (IIEF >22) was reported by 45/58 (78%) and 39/58 (68%) patients,
      respectively. DISCUSSION AND CONCLUSIONS. The recovery of EF was good one year
      after BT (78%). Urinary disorders are a significant limiting factor on this
      recovery. The deterioration of EF during the follow-up, which was already
      described in literature, is due not only to ageing but also to a delayed
      radioactive effect on pelvic structures.

PMID- 21086313
TI  - [Multilocular cystic renal cell carcinoma: our experience].
AB  - Multilocular cystic renal cell carcinoma is now recognized as an independent
      pattern by WHO; it is a rare malignancy with a predominantly cystic growth,
      characterized by very low oncologic evolution and then susceptible to
      conservative treatment. In the kidney cystic masses of different origin may
      arise, i.e. due to malformation, acquired disease or tumor. Renal neoplastic
      lesions may have a cystic or pseudocystic component. There are also four types of
      neoplasm with a predominantly cystic growth, including the multilocular cystic
      carcinoma, which are macroscopically very similar and impossible to differentiate
      through diagnostic pre-operative images. The Authors present four cases of
      multilocular cystic renal cell carcinoma diagnosed in the 2000-2007 period, with
      special reference to diagnostic difficulties and to pre- and intra-operative
      features of the neoplasm. In conclusion, the extemporaneous histological
      preoperative diagnosis of multilocular cystic renal cell carcinoma is not
      possible because it requires extensive sampling; furthermore, the final
      histological diagnosis sometimes needs particular immunohistochemical procedures
      to be confirmed.

PMID- 21086314
TI  - [Oncological and functional results of laparoscopic radical prostatectomy after
      100 procedures: our experience].
AB  - Laparoscopic radical prostatectomy plays an emerging role in the surgical
      management of prostatic tumors. We present our experience of the first 100 cases
      of extraperitoneal laparoscopic radical prostatectomy. Our results about
      continence, erectile function and surgical margins are reported. MATERIALS AND
      METHODS. Between January 2005 and December 2007, 100 laparoscopic radical
      prostatectomies were performed by one surgeon. We retrospectively reviewed
      margins status, operative time, blood transfusion rates, time of catheterization,
      length of hospital stay, continence and potency rates. RESULTS. The operative
      time decreased during the learning curve. The mean duration of surgery was 240
      minutes (in the first 25 procedures the median time was 320 minutes, while in the
      last 25 cases the mean duration was 200 minutes). Five conversions to open
      surgery were required owing to failure to progress. The overall rate of positive
      surgical margins was 15% in pT2 and 35% in pT3a tumors. We had 3 minor
      complications (two anastomotic leakage and one hemorrhage from the anastomosis)
      and 2 major complications (recto-urethral fistula). The mean intraoperative blood
      loss was 450 ml (range 200-1500). With regard to transfusion, 25 patients (25%)
      received their autologous units, while 2% of the patients required homologous
      units. The mean duration of catheterization was 7.8 days. The continence rate at
      12 months was 85%; the potency rate was 55% at 12 months. CONCLUSIONS. The
      results of the present study show that by using a rational approach to training,
      a general urologist with low experience in laparoscopy is able to safely perform
      laparoscopic radical prostatectomy, and with oncological and functional results
      comparable to those of other published series.

PMID- 21086315
TI  - [Coexistence of different histotypes of renal carcinoma:our experience and
      literature review].
AB  - The coexistence of multiple, synchronous primary tumors of different histology
      within the same kidney is a rare condition. We report herein a series of five
      patients with two tumors of different histology involving synchronously the same
      kidney. MATERIALS AND METHODS. We reviewed the pathology reports of a series of
      381 patients who underwent surgery for primary renal tumors at our institution
      from 2000 to 2007. In the files of all patients with synchronous tumors of
      different histology, special attention was given to the results of imaging
      studies. RESULTS. Five out of 381 patients (1.37%) had coexistence of two primary
      tumors of different histology within the same kidney. Four patients had
      ultrasonography as the first imaging procedure, one patient had ultrasonography
      as the second imaging procedure; all had preoperative CT of the abdomen. Both
      lesions were detected by preoperative CT in 4/5 of the cases; in the remaining
      one, the smaller lesion was not visible, even in retrospect. CONCLUSIONS. The
      coexistence of multiple and synchronous primary tumors of different histology
      within the same kidney has been only rarely described. To the best of our
      knowledge, in literature there are only case reports with the exception of a case
      of renal oncocytoma with evolving papillary RCC. We believe that this condition
      could be more frequent if the radiologist and the anatomopathologist try to find
      it.

PMID- 21086316
TI  - [Testicular localization of extranodal multifocal non-Hodgkin lymphoma. Report of
      two cases, review of the literature and clinical considerations].
AB  - The aim of our study is to describe two cases of testicular localization of non-
      Hodgkin Lymphoma associated with the involvement of other extranodal organs, and
      to investigate the possible causes of this association according to the evidences
      found in literature. Non-Hodgkin Lymphoma is extranodal in 25% of cases. Most of
      the times the organs involved are stomach, bowel, skin, central nervous system.
      About urological localizations, the most common is testis. Very rare is to find
      lymphoma in kidney, prostate, urinary bladder, and ureter. Testicular lymphoma is
      about 5% of testis malignancies; it is more frequent in the 7th and in the 8th
      decade. Metastases of testicular non-Hodgkin lymphoma are described also many
      years later, and also in distant organs. Primary forms are usually "diffuse large
      B cell", a high-grade histotype; metastatic ones often show Burkitt cells. The
      standard therapy used for non-Hodgkin Lymphomas does not reach testis and central
      nervous system, so that these sites are called "Therapeutic Shrines". Therefore,
      in order to prevent testicular localization, it is necessary to use radiotherapy,
      and for nervous system prophylaxis it is necessary to administer intrathecal
      chemotherapy. More than one localization of non-Hodgkin lymphoma simultaneously
      found may indicate not only a metastatic spread, but also a multicentric origin.
      We describe two patients who had one testis removed because of a big mass that
      turned out to be a non-Hodgkin lymphoma. The first patient had been treated for a
      non-Hodgkin lymphoma of maxillary sinus 20 months before. The second patient
      showed contemporary involvement of other organs. In both cases the different
      localizations of non-Hodgkin lymphoma showed the same histological features and
      cellular immunophenotype. It is important to underline that in the former patient
      staging TC, repeated many times, had always been negative, but physical
      examination of testis had been omitted, so that sinonasal localization, assumed
      to be the first one, really might have been the spread of an undetected testis
      lymphoma. In conclusion, in case of extranodal non- Hodgkin lymphoma or any other
      malignancies, manual or ultrasound examination of testis should never be omitted,
      because standard techniques of staging (TC, RMN, PET) cannot explore this organ.

PMID- 21086317
TI  - [A rare case of female splenogonadal fusion].

PMID- 21086318
TI  - [Evolution of our experience in diagnosis and therapy for urinary infections].

PMID- 21086319
TI  - [The use of flexible cystoscope in posterior urethroplasty].

PMID- 21086320
TI  - [Transperitoneal laparoscopic radical nephrectomy for a 12 cm renal mass].

PMID- 21086321
TI  - [Severe case of male external genitalia injury in a polytraumatized patient].

PMID- 21086322
TI  - [A rare case of female bladder spontaneous rupture].

PMID- 21086323
TI  - [Endocavitary prophylaxis of superficial urothelial bladder tumours: new
      compounds].
AB  - Bladder urothelial carcinoma is the fourth most frequent cancer among European
      men, accounting for about 7% of the total cancers. Transurethral resection (TUR)
      is usually indicated as the standard treatment for non-muscle invasive bladder
      cancer (NMIBC). However, TUR is unable to guarantee a complete eradication of Ta,
      T1 tumors with a recurrence rate ranging from 50 to 70%, and a progression rate
      to muscle invasive disease ranging from 10 to 15%. METHODS. The European
      Association of Urology guidelines recommend adjuvant intravesical chemotherapy
      after definitive diagnosis of intermediate/high risk NMIBC to reduce both
      recurrence and progression of the disease. To provide a comprehensive review of
      intravesical treatment options for NMIBC, we performed a search of the PubMed
      database for articles between 1980 and 2009 that reported on intravesical agents
      for treating this disease. RESULTS. A critical analysis of the findings resulting
      from large multicenter trials, phase I, II, III studies for pertinent novel
      agents and from review articles was carried out. We focused on the following
      issues: 1) the role of the treatment with Bacillus Calmette-Guerin (BCG) and the
      need of maintaining the drug schedule (with or without interferon- alpha); 2) the
      correct timing of adjuvant immuno- and chemotherapy; 3) the use of the novel
      chemotherapeutic agents; 4) the use of the novel technique of chemotherapeutic
      agents administration, with a particular interest on electromotive administration
      of mitomycin.

PMID- 21086324
TI  - [Contrast media in urogenital radiology].
AB  - BACKGROUND. Contrast media are widely used in urogenital radiology. The ideal
      contrast agent should be totally inert, causing no interactions with organism,
      and with a rapid and complete excretion. Adverse reactions could occur after
      using any type of contrast media. Contrast enhanced procedures are performed with
      increasing frequency and the patients population is progressively older and with
      multiple co-morbid conditions, thus contrast media toxicity is becoming a serious
      problem. Contrast media-induced nephropathy (CIN) is considered an important
      cause of hospital-acquired renal failure. The administration of gadolinium-based
      contrast agents has been recently associated with the development of a serious
      adverse reaction, potentially lethal in patients with renal insufficiency, named
      nephrogenic systemic fibrosis (NSF). METHODS. Literature review on contrast media
      in urogenital radiology, CIN, NSF. CONCLUSIONS. Since 1996, the Contrast Media
      Safety Committee of the European Society of Urogenital Radiology (ESUR) has
      released its guidelines regarding safety about the use of contrast media. CIN,
      and the emerging NSF, are topics of increasing interest for urologists,
      radiologists, nephrologists, dermatologists and all the clinicians. Contrast
      media have progressively become safer in the last years. Even if rare, some
      adverse reactions still occurr up to now. CIN and its prevention remain an issue
      under debate. In the past, whenever a patient required a contrast-enhanced
      imaging study, the trend was to select magnetic resonance imaging with gadolinium
      based contrast agents in order to avoid the well-known CIN of iodinated-based
      contrast agents. The awareness of NFS is changing the contrast-enhanced imaging
      in patients with renal failure. At present we have to investigate NSF
      etiopathogenesis, in order to prevent and eventually to cure it. The
      understanding of the risk factors for both CIN and NSF is an emerging need, the
      adoption of all preventive measures to reduce the risks remain a mandatory issue.

PMID- 21086325
TI  - [Management, and prevention, of intravesical therapy complications].
AB  - The urologist must prevent, identify and properly treat the complications of
      intravesical chemotherapy and immunotherapy. Both local and systemic toxicity of
      adjuvant intravesical therapy is herein analyzed. Topical toxicity is mainly due
      to the inflammation induced by the contact between the instilled agent and the
      bladder mucosa. MATERIAL AND METHODS. The factors predisposing to topical
      toxicity must be identified and removed before starting the treatment. The choice
      of the agent, its dose, concentration and dosage must be tailored, whenever
      possible, to the presence of the above mentioned factors. Mitomycin and BCG can
      rarely provoke chronic cystitis, severely compromising bladder function. RESULTS.
      The most dangerous complication of early intravesical chemotherapy is the
      instillation in presence of an unrecognized bladder perforation. Flu-like
      syndrome, fever, chills, arthralgia are reported in almost 20% of patients
      receiving BCG. If fever persists for more than 48 hours or exceeds 38.5  degrees
      C, isoniazid must be administered and BCG stopped until complete remission. BCG
      sepsis is a rare but severe complication that must be promptly recognized and
      treated. If not, a life-threatening multi-organ failure syndrome can arise.
      Isoniazid and rifampicin, adding ethambutol when required, must be administered
      for a prolonged period until complete remission. CONCLUSIONS. Granulomatous
      lesions represent the main other rare systemic complications of BCG therapy.
      Systemic toxicity of intravesical chemotherapy is rare, due to the high molecular
      weight of the drugs, limiting systemic absorption.

PMID- 21086326
TI  - [a-blockers in benign prostatic hyperplasia: the problem of "floppy iris
      syndrome". Results of a case-control study to evaluate the surgical risk through
      the meausurement of pupil diameter].
AB  - OBJECTIVES. alpha-blockers are a group of alpha-adrenoceptor antagonists used by
      urologists to treat lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia. Recent studies have suggested that these drugs - tamsulosin in
      particular - are involved in the development of iris complications during
      phacoemulsification. The objective of this study is to investigate the effects of
      alpha-blockers - especially tamsulosin - on pupil diameter. MATERIALS AND
      METHODS. We measured the photopic, mesopic and post-dilatation pupil diameters in
      both eyes of 24 patients (46 eyes in total), 16 of them treated with alpha
      blockers and 8 of them (16 eyes in total) not treated with any drugs (controls).
      RESULTS. All patients treated with tamsulosin showed minor photopic, mesopic and
      post-dilatation diameters compared to controls. Patients treated with other alpha
      blockers did not show any difference compared to controls. CONCLUSIONS. Even if a
      small number of eyes was evaluated, our study shows that tamsulosin - through its
      selective effect on alpha1A receptors - is the most involved drug in the
      Intraoperative Floppy Iris Syndrome.

PMID- 21086327
TI  - [Living donor nephrectomy: open versus laparoscopic technique].
AB  - The living donor nephrectomy has to be safe and effective, allowing a good graft
      function in the recipient. In the past, donor nephrectomy was performed only by
      open technique; more recently this nephrectomy has also been performed by
      laparoscopic technique. The best technique has not been established in
      literature. The purpose of this study is to report the results of open and
      laparoscopic nephrectomy in living donors. MATERIALS AND METHODS. From January
      1992 to August 2008, 37 living donor nephrectomies were performed. 23
      nephrectomies were achieved by laparoscopic procedure (LDN) and 14 by open
      technique (ODN). The 2 groups were comparable regarding both donor and recipient
      characteristics. RESULTS. All laparoscopic nephrectomies were successfully
      performed without conversion to open procedure. No donor deaths were reported in
      either groups. 3 complications (13%) in the LDN group and 1 (7.1%) in the ODN
      group (p=0.6) were observed. Mean operative time was higher in the LDN group
      (p<0.036). Mean warm and cold ischemia time, resumption of oral intake and
      hospital stay were shorter in the LDN group (p<0.04)( p<0.03) (p<0.0001), whereas
      the return to normal occupational life was similar (p<0.52). We had no
      significant differences in the surgical complication rates, graft and patient
      survival. CONCLUSIONS. Our experience suggests that both procedures can be used
      safely and efficiently, and assure a good renal function in the recipient.
      Laparoscopic nephrectomy, although more difficult, provides post-operative
      advantages. However, laparoscopic procedure must be performed by experienced
      centres only to prevent serious complications in the donor.

PMID- 21086328
TI  - [Brachytherapy in prostate cancer: the use of QuickLink(r) system within the real
      time technique. A new technique is presented].
AB  - INTRODUCTION. Brachytherapy with real-time technique allows the ultrasound
      transperineal implant of needles and the release of I125 seeds in the prostate,
      with intraoperative dosimetry carried out by a special software. After performing
      this seed-releasing technique on 160 patients, we present 15 cases treated with
      strand seeds using the QuickLink(r)system. MATERIALS AND METHODS. INCLUSION
      CRITERIA: CaP clinical stage T1-T2, PSA <=10 ng/ml, prostate volume <= 50g,
      Gleason score <=3+3=6, Q maximum >13-15 ml/sec., and I-PSS score <10. METHODICAL.
      In ultrasound-guided transrectal technique the needles are inserted near the
      prostatic capsule. A 5mm section plan is performed; the computer allows
      identifying the contours of prostate, rectum, urethra, and the position of
      needles to be inserted. The total activity is defined, as well as the number and
      location of the sources to be included; isodoses are calculated, the correct
      position of seeds and spacers is printed. The strand seeds are prepared on the
      basis of this scheme, using the QuickLink(r) system, and placed into the prostate
      tissue. RESULTS. The QuickLink(r) system allows reducing the operative time (110
      min, range 95-125). The pelvic CT assessing the post-planning has shown a more
      regular distribution of seeds. The cut-off of D90>=140 Gy was reached in all
      patients, with doses at urethra and rectum within the prescribed limits.
      CONCLUSIONS. The brachytherapy real-time with strand seeds QuickLink(r) combines
      the flexibility of planning intraoperative real-time with a faster process, and
      less tendency for the relocation of the seeds.

PMID- 21086329
TI  - Bulking agents: anesthesia techniques.
AB  - Bulking therapy for the minimally invasive treatment of stress urinary
      incontinence (SUI) may be offered to women with urodynamic SUI, wishing to avoid
      the complications associated with more invasive surgery, on the basis of low
      operative morbidity and low longterm success rates. These bulking agents may be
      injected by a retrograde or antegrade technique in the periurethral tissue around
      the bladder neck and proximal urethra. This therapy is strongly dependent on the
      anesthetic technique of choice; moreover its application as an outpatient
      procedure implies the potential for a cost-effective treatment for selected
      patients with SUI. In the present paper all factors affecting the choice of
      different types of anesthetic techniques are discussed.

PMID- 21086330
TI  - [Segmental testicular infarction. Report of two clinical cases and literature
      review].
AB  - Segmental testicular infarction is rare. To the best of our knowledge forty cases
      are reported in literature. We present two cases of segmental testicular
      infarction with different etiology. The first case was observed after
      herniorrhaphy and varicocelectomy. The second one occurred after acute
      epididymitis. Both cases have been treated without radical orchiectomy. We have
      also reviewed the pertinent literature in terms of differential diagnosis,
      etiology and management, with particular regard to testicular sparing.

PMID- 21086331
TI  - Iliac artery-ureteral fistula: a fatal hemorrhage in a man with
      ureterocutaneostomy.
AB  - Primary and secondary artery-ureteral fistulas are a rare condition. In this case
      report we describe a case of misunderstood iliac artery-ureteral fistula, with
      negative radiological preoperative imaging, which occurred in a man as late
      complication of ureterocutaneostomy.

PMID- 21086332
TI  - [Scrotal masses: considerations on two cases of epididymal tumors].
AB  - The scrotum is a fibromuscular sac that contains the testis, epididymis,
      spermatic cord and the associated fibrous coatings. All these components can be
      affected by different variety of pathologic phenomena, including congenital,
      inflammatory and neoplastic events. When a scrotal mass is observed, there are
      two basic questions to be answered, i.e. if the mass is intratesticular or
      extratesticular, and if it is of cystic or solid nature. Apart from a few rare
      exceptions, intratesticular solid masses should be considered malignant, while
      extratesticular masses with liquid content are generally benign. CASE REPORTS.
      Two cases of tumor are hereby presented: they originated from the epididymis, and
      their clinical presentations did not allow making a differential diagnosis
      between benign and malignant tumor during the preoperative examinations. After
      presenting the diagnostic doubts to patients, and once obtained their informed
      consent, surgeries were performed allowing for a precise histological diagnosis,
      and at the same time, proving to be also valid therapeutic tools.

PMID- 21086333
TI  - [High-intensity focused ultrasound and prostate cancer: technology, state of the
      art and future].
AB  - BACKGROUND. The potential applications of the high-intensity focused ultrasound
      (HIFU) as a minimally invasive therapy of the localized prostate cancer explain
      the growing interest of the urologic community towards this technique. HIFU has
      been assessed for its role in the treatment of localized prostate cancer in
      patients who otherwise would not have benefited from surgery, and in local
      recurrences after radiation failure. Methods. Relevant information on HIFU
      treatment was identified through a literature search of published studies.
      RESULTS. High biochemical efficacy, excellent tumor local control and favorable
      mid- and long-term oncological data with a low morbidity rate have been shown in
      many series of patients. CONCLUSIONS. Although HIFU is a recent and emerging
      technology, it has been well studied and developed to a point that HIFU will
      undoubtedly be an effective alternative to radiation therapy.

PMID- 21086334
TI  - [Methodology of clinical trials for non-muscle infiltrating bladder cancer.
      Objective evaluation: standardization requirements].
AB  - The formulation of proper evaluation criteria after superficial bladder cancer
      therapy poses several methodological problems that are often peculiar to the
      disease. The Achilles' heel of many trials is possibly found in the criteria used
      for the evaluation of the trial outcomes. As a consequence of that, total
      agreement regarding the criteria for response and the evaluation of response is
      needed. The adoption of standard response criteria should be given high priority.
      Uniform response criteria should be chosen because they meet standards of
      reliability and statistical validity. Thus, the criteria must be reproducible,
      and they should correlate with some measures of patient's benefit, such as
      quantity and quality of survival. A proposal of standardization in superficial
      bladder cancer clinical trials is presented based upon current knowledge on the
      methodology for conducting clinical trials and upon the experience coming from
      major clinical research groups.

PMID- 21086335
TI  - [Intravesical Electromotive Drug Administration(r)(EMDA)with Mitomycin-C for non
      muscle invasive bladder cancer].
AB  - Electromotive Drug Administration(r) (EMDA) offers a means of controlling and
      enhancing the tissue transport of certain drugs, when applied to a surface
      epithelium, where they have a local therapeutic effect, in order to increase
      their efficacy. One application option is the treatment of non-muscle invasive
      bladder cancer with intravesical mitomycin-C (MMC). Laboratory studies
      demonstrated that EMDA/MMC can reduce the variability and enhance the drug
      administration rate into all layers of the bladder wall, and that the applied
      electric current causes no histological damage to tissue and no chemical
      modification of MMC. A prospective randomized study, performed in patients with
      in situ carcinoma, validated the prediction that electromotive enhancement of MMC
      delivery would provide results superior to those achieved using passive MMC
      transport. A further randomized study in patients with pT1 bladder cancer
      demonstrated that a regimen combining intravesical BCG and EMDA/MMC increased the
      disease-free interval and reduced the recurrence rate, as well as the disease
      progression and mortality rate if compared with BCG alone. The possibility that
      BCG may enhance the efficacy of MMC against high-grade pT1 transitional cell
      carcinoma and in situ carcinoma represents an important new therapeutic
      perspective in the high-risk non-muscle invasive bladder cancer.

PMID- 21086336
TI  - [Transvesical prostatic adenomectomy: general or local anesthesia].
AB  - A transvesical prostatic adenomectomy is defined as an "open-sky" surgical
      procedure performed to remove a benign prostatic nodule that, growing up, could
      represent an obstacle to the normal emptying of the bladder. This operation can
      be carried out under general or loco-regional anesthesia conditions: the second
      option, however, does not provide the curarization of the patient, and could
      result in a higher endoabdominal pressure, which could significantly reduce the
      surgeon's visual field. Nevertheless, this technique allows for a complete
      analgesia and anesthesia during the first postoperative hours, avoiding the
      occurrence of abdominopelvic contractions and pain-linked hypertension, which can
      cause dangerous postoperative bleedings. As opposed to this, during surgery under
      general anesthesia conditions, the curarization ensures a wider operating field,
      free from abdominopelvic contractions, but with important postoperative pain, the
      main cause of which is the continuous bladder washing; this kind of pain is very
      difficult to treat even with oppioids: it is certainly the most important cause
      of bleedings, resulting in patient's discomfort, risk of blood transfusion or
      even reoperation. The two techniques have been compared in a randomized study on
      40 patients: the subarachnoid technique seems definitely to be more favorable,
      with its optimal antalgic effect even during the first postoperative hours, with
      no need to use high doses of antalgic iv drugs, and, most important, with no
      subsequent postoperative hypertension and bleedings.

PMID- 21086337
TI  - [Anatomy and nerve supply of the pelvic floor].
AB  - In order to guarantee urinary and fecal continence as well as correct pelvic
      statics, the perfect neuroanatomical integrity of the pelvic floor muscles is
      mandatory. As Dickinson stated: "There is no considerable muscle in the body
      whose form and function are more difficult to understand than those of the
      levator ani, and about which such nebulous impressions prevail". Clinical
      implications of pelvic floor anatomy and nerve supply are evident: a denervation
      of this muscle group and the consequent muscle dysfunction could result in
      urinary and/or fecal incontinence, as well as pelvic organ prolapse.

PMID- 21086338
TI  - [TVT and TOT: a comparison between these two techniques based on our clinical
      experience].
AB  - AIM OF THE STUDY: A retrospective evaluation and a comparison of results from two
      minimally invasive surgery techniques that we adopted for the treatment of SUI.
      MATERIALS AND METHODS. In this study we evaluated 113 selected patients who
      underwent SUI minimally invasive surgery from 1-1-2000 to 31-12-2007. 87 patients
      underwent epidural anesthesia. 26 local anesthesia. In Group A (TVT) 61 patients
      were enrolled, mean age 57.6 (+/-22). 43 patients (70%) were on menopause. In
      Group B (TOT out-in) 52 patients were enrolled (for 34 of them we used the
      Obtape(r) sling while for 18 the Obtryx(r) one), their mean age was 58.5 (+/
      20.5) and 39 patients (75%) were on menopause. Patients from both groups did not
      undergo any past previous urogynecological surgery and suffered from stress
      urinary incontinence with cervico-urethral hypermobility butno other associated
      pathology. The pre-operative work-up included an evaluation of patients based on
      ICS guidelines. RESULTS. Group A (TVT) - mean follow-up 66.3 months, dry patients
      53/61 (86.8%). Bladder perforations resolved by catheterization 3/61 (5%).
      Transient voiding dysfunction 14/61 (22.8%). "De novo" urgency 8/61 (13%). One
      patient on self-catheterization due to persistent urinary retention underwent a
      single-side section of the sling with spontaneous micturition and complete
      continence recovery. Group B (TOT out-in) - mean follow-up 35.5 months, dry
      patients 43/52 (82%). 4 patients (7.6%) complained oftransient voiding
      dysfunction, 5 patients (9.5%) for "de novo" urgency, 1 patient underwent a sling
      removal due to vaginal erosion 4 months after surgery (Obtape(r)).

PMID- 21086339
TI  - [Stone Cone(r) in ureteroscopic ballistic lithotripsy of proximal ureteral
      stones].
AB  - Stone Cone(r) (Microvasive-Boston Scientific Corp, USA) is a device which
      prevents retrograde calculus migration during endoscopic ureterolithotripsy. We
      have studied the safety and efficacy of this device in endoscopic
      ureterolithotripsy with ballistic energy in proximal ureteral stones. MATERIALS
      AND METHODS. From 01/02/2006 to 01/02/2008 we carried out 36 ureterorenoscopies
      (URS) for proximal ureteral stones (average age: 46, range: 15-73). A ballistic
      energy was used for stones fragmentation. In 18 patients (Group A) we carried out
      URS with the aid of Stone Cone(r), which was not used in the other 18 patients
      (Group B). Semirigid 8 Ch or 10 Ch Storz ureteroscope and ballistic lithotriptor
      Swiss Lithoclast Master EMS(r) were used. In cases of migration, edema, and
      ureteral damage, a ureteral stent was used. RESULTS. In Group B patients (URS
      performed without Stone Cone(r)) the migration of the whole stone, or of
      clinically significant fragments, occurred 8 times (45%). All of these patients
      underwent external shockwave lithotripsy (ESWL) at a center equipped with a
      lithotriptor. A ureteral stent was placed in 14 cases (78%). In Group A, the
      migration of a stone requiring ESWL treatment occurred only once (5%). The
      ureteral stent was placed 8 times (45%). We had no significant complications
      during the procedure. CONCLUSIONS. The Stone Cone(r) is a safe and easy-to-use
      device. The cost of this device can be balanced by the reduction of postoperative
      ESWL treatments for lithiasic fragments pushing up into the kidneys (p<0.01), and
      of ureteral stent applications at the end of the procedure (p<0.05).

PMID- 21086340
TI  - [Renal cell carcinoma associated with incidental presentation of renal artery
      aneurysm: surgical management].
AB  - The Renal Artery Aneurysm (RAA) is a relatively uncommon vascular lesion. A renal
      artery disease coexisting in patients with Renal Cell Carcinoma (RCC) is an even
      more infrequent clinical presentation. We reported on the treatment of a rare
      case of incidentally intraoperative renal artery aneurysm discovered during a
      nephron-sparing surgery for RCC. After the surgery the patient did not need
      hypertension therapy any longer. This event is well-known, in fact a number of
      possible contributions to a renin-mediated hypertension management has been
      postulated.

PMID- 21086341
TI  - [Adenoid cystic/basal cell carcinoma of the prostate:case report].
AB  - Although most prostate carcinomas belong to the conventional acinar type, unusual
      variants have been reported. The adenoid cystic/basal cell carcinoma of the
      prostate is a rare tumor with distinctive histopathologic features. There are
      quite few publications in the literature concerning the diagnosis, treatment, and
      prognosis of this neoplasm. METHODS. A 71-year-old man had an increased PSA value
      (5.11 ng/dL); the prostatic biopsy examination was positive for adenoid
      cystic/basal cell carcinoma. For this reason we proceeded with radical
      prostatectomy. The histology examination showed an acinar conventional carcinoma
      and adenoid cystic/basal cell carcinoma. At eight months the patient did not show
      any recurrence. CONCLUSIONS. Various histologic and immunohistochemical features
      are helpful in recognizing the adenoid cystic/basal cell carcinoma of the
      prostate. Clinically, the only difference from a conventional adenocarcinoma is
      that the PSA value is usually normal or only slightly increased. This tumor has a
      biological potential that can result in metastases in some cases; the current
      treatment consists primarily in the surgical resection. A close, long-term follow
      up is strongly recommended.

PMID- 21086342
TI  - [Update on epidemiology and risk factors of prostate cancer].
AB  - Prostate cancer is one of the most common malignancies in the world; more and
      more men are being diagnosed with prostate cancer worldwide. According to
      epidemiological studies, prostate cancer will become the most common male cancer
      by 2010, with 900,000 cases per year. Nevertheless, although the constant
      increase in incidence, knowledge about the aetiology and risk factors of this
      tumour is still poor. Several important issues could foster the understanding and
      prevention of this disease, such as the variation in incidence of prostate cancer
      between ethnic populations, studies on migrants, dietary and genetic factors.
      Here we provide an update on epidemiology and risk factors of prostate cancer.

PMID- 21086343
TI  - Putative tissue markers in prostate cancer*.
AB  - A variety of putative prostate cancer markers have been described in human serum,
      urine, seminal fluid, and histological specimens. These markers exhibit varying
      capacities to detect prostate cancer and to predict disease course. In order to
      be considered markers for diagnosis or prognosis of disease course, and to be
      brought forward for large-scale clinical evaluation, they should fulfill several
      criteria. Firstly, there should be a biological or therapeutic rationale for
      choosing the marker, or at least a consistent association with disease presence,
      disease characteristics such as stage, or disease aggressiveness. Secondly, there
      should be an assessment of the strength of marker association with disease
      outcome. Thirdly, the marker should be assessed as an independent predictor in a
      multivariate analysis.

PMID- 21086344
TI  - [Minimal invasiveness of radical laparoscopic prostatectomy:dreams or reality?].
AB  - To determine the systemic response to extraperitoneal laparoscopic (eLRP) and
      open retropubic radical prostatectomy (RRP). MATERIALS AND METHODS. In all, 430
      patients who had eLRP (200) or open RRP (230) were recruited; patients in both
      groups had similar preoperative staging. In addition to peri-operative variables
      (operative duration, complications, blood loss, transfusion rate,
      hospitalization, catheterization), oncological data (Gleason score, pathological
      stage, positive margins) were also compared. The extent of the systemic response
      to surgery-induced tissue trauma was measured in all patients, by assessing the
      levels of acute-phase markers C-reactive protein (CRP), serum amyloid A (SAA),
      interleukin-6 (IL-6) and IL-10 before, during and after RP. RESULTS. The duration
      of surgery, transfusion rate, hospital stay and duration of catheterization were
      comparable with those of previous studies. There was an increase in IL-6, CRP and
      SAA but no change in IL-10, and no differences between eLRP and RRP over the
      entire period assessed. CONCLUSION. The invasiveness of eLRP could not be
      substantiated objectively on the basis of the variables measured in this study.
      The surgical trauma and the associated invasiveness of both methods were
      equivalent.

PMID- 21086345
TI  - [A 7-case anatomopathology revision in the presence of renal relapse after
      conservative therapy: implications on surgical technique].
AB  - Anatomopathology revision of the cases which underwent second surgery because of
      a renal neoplasm relapsing after conservative surgery, in order to find possible
      relations with the surgical technique. MATERIALS AND METHODS. At our institution,
      Nephron-sparing surgery (NSS) is currently indicated as elective technique for
      neoplasms smaller than 4cm in diameter. The technique involves the removal of the
      neoplasm with a margin of healthy parenchyma and with the perilesional fat. The
      patients are monitored with a first CT check after 4 months and then with
      ultrasound/CT checks every 6 months in the first 2 years and then once a year. In
      the present study we analyze the records of the cases in the period 1994-2005
      undergoing a second operation for a renal tumor relapsing in the operated kidney
      after NSS. All specimens were reviewed by a single experienced uro-pathologist,
      who determined the size of the surgical margins and the relations between the
      seat of recidivism and the seat of the preceding enucleoresection. RESULTS. Seven
      cases with renal relapse were found out of 267 undergoing conservative surgery in
      the same period (incidence: 2.6%). The diagnosis had always been made lacking any
      other disease localizations at a complete re-staging; the average relapse latency
      was 19.4 months (8-46 months). In 5 cases the second tumor was found in the seat
      of the previous NSS: for these cases the minimum margin of the enucleoresection
      was lower than 3mm (median minimum margin: 1.6 mm). Differently, in the remaining
      2 cases, both with a wider surgical margin (median minimum margin: 12.0 mm), the
      seat of the first and that of the second neoplasm were distant. In particular, in
      one case a multifocal relapse with a spread microvascular embolization was found,
      while in the other the two neoplasms showed a different histotype. DISCUSSION AND
      CONCLUSIONS. In the 5 cases with a little resection margin and relapsing tumor in
      the seat of the enucleoresection, the persistence of a peritumoral microscopic
      neoplastic disease can be assumed. In the other 2 cases showing a wider surgical
      margin the relapse can be attributed to the widespread microscopic multifocality
      in one case, and to the development of a second de novo neoplasm in the other
      case. The extension of the surgical margin seems then to have played a role in
      determining a relapse in the seat of enucleoresection.

PMID- 21086346
TI  - Erectile dysfunction and alcohol intake.
AB  - The objective of this work is to evaluate in a selection of patients with
      erectile dysfunction the influence of alcohol consumption and the response to
      alcohol abstinence with and without sildenafil association. Materials and
      Methods. In a population of 150 consecutive patients with erectile dysfunction we
      studied 50 patients aged between 22 and 77 years (mean 56+/-14 SD). These 50
      patients were divided into three different treatment groups and were screened for
      three different levels of alcohol risk with two questionnaires. All patients were
      evaluated with an International Index Erectile Dysfunction (IIEF) questionnaire
      before and after one month of treatment. RESULTS. The 50 patients included 14
      patients with high alcohol risk, 34 patients with low alcohol risk and only 2
      patients with no alcohol risk. After one month, 29 patients responded to the
      therapy, and 21 did not respond. The IIEF questionnaire presented a statistically
      significant difference between the different risk groups before and after
      treatment (p<=0.05). All the patients were examined with a penile Doppler
      Ultrasound. Only 10 of them had an abnormal diastolic peak velocity (PDV) and
      only 1 presented both pathologic systolic peak velocity (PSV) and PDV. These 11
      patients did not respond to therapies and 10 of them were at high alcohol risk.
      The alcohol consumption risk was directly correlated with PDV (p=0.00001;
      R2=0.4). CONCLUSIONS. The results of this study demonstrated a significant
      relationship between alcohol consumption and erectile dysfunction. This
      underlines the important therapeutic issue of alcohol abstinence in treating
      patients with erectile dysfunction.

PMID- 21086347
TI  - Bladder and buccal mucosa graft in urethral stricture reconstruction.
AB  - Purpose. Our aim was to determine the success of urethroplasty using a free graft
      of buccal or bladder mucosa for the treatment of complex anterior urethral
      stricture in adults. MATERIALS AND METHODS. From October 2000 to February 2005,
      11 patients with complex anterior urethral stricture underwent substitution
      urethroplasty, using mucosal grafts, 6 buccal and 5 bladder. RESULTS. The mean
      follow-up time was 50 months for 8 out of 11 patients (range 24 to 72). The
      procedure was successful for 6 patients (75%). Urethral stricture recurred in 2
      patients (25%) and was treated by urethrotomy or meatoplasty with positive
      outcomes. CONCLUSION. Our limited experience with the reconstruction of a complex
      stricture of the anterior urethra confirmed that buccal and bladder mucosa grafts
      are excellent materials for substitution urethroplasty but that case selection is
      important.

PMID- 21086348
TI  - [Echo-assisted percutaneous nephrolithotomy in the supine position. Technical
      notes].
AB  - The adoption of supine position in percutaneous nephrolithotomy and the routine
      use of echography during the procedure allow for a reduction of surgical time,
      radiological exposure of patient and surgeons, and of anaesthesiological risks;
      moreover, it permits a combined anterograde-retrograde approach to the kidney in
      case of very complex lithiasis. The urologist's knowledge and experience of
      echography devices allows for a high lowering of the learning curve time.

PMID- 21086349
TI  - [Therapeutic education in urology: a fundamental resource for the sick and the
      health carers].
AB  - Therapeutic Education (TE) means to build a partnership between doctors and
      patients comparing knowledge and therapeutic procedures to manage the disease and
      its treatment. Patients cannot be a mere passive beneficiary of therapeutic
      services, but they must play an active role, be conscious and participate in
      charging proper and community health. Patient TE is a pathway characterized by an
      "educational diagnosis" including identification of patient demands about
      pathology; an "educational-therapeutic policy" based on assignment of tasks and
      rules to manage every aspect of pathology; and the "evaluation" of results of
      patients' educational process. The aim of TE is to allow the patients to know
      their pathology, to properly perform therapeutic procedures, to self-manage and
      prevent complications and to adopt a correct lifestyle. It can be useful to
      organize theoretical and practical lessons reserved to groups of patients. TE can
      be applied to urologic pathologies. These pathologies are often chronic diseases
      and affect elderly patients, who are organically and psychologically fragile.
      Urologic patients must often manage urostomies, urinary drains, complex follow-up
      plans. The patients' learning about procedures and disease management represents
      a professional duty of the urologic team: bladder and prostate cancer, urinary
      drains management are fields where we can apply a TE plan to support and
      safeguard the patients' health.

PMID- 21086350
TI  - [Acute thrombosis of the renal artery secondary to closed abdominal trauma: our
      experience and literature revision].
AB  - AIM: Thrombosis secondary to renal closed abdominal trauma is a rare event, most
      of the time it is clinically silent. We report here our experience. MATERIALS AND
      METHODS. This is the case of a boy came to our observation after a road trauma
      with motorbike fall-out. The boy arrived in ED for head injury. The patient,
      stable for haemodynamics, had lacerated and contused injuries at pelvis and right
      buttock level. He underwent chest x-rays, brain CT and neurosurgery examination:
      all resulted negative. There was no macrohematuria, nor lumbar pain. Objectively
      abdomen was treatable. The patient was referred to temporary observation for 12
      hours when he was asked to undergo abdomen ultrasound, which showed no documented
      lesions except for fluid collection at the pelvic level. To rule out all doubts,
      the patient had an abdominal CT scan, which showed a silent left kidney with
      suspected thrombosis at left renal level. The patient was sent to our attention
      after 15 hours: we decided to perform immediately selective arteriography with
      thrombus lysis. The arteriography documented a massive thrombosis. The thrombus
      lysis was impossible to be performed. To maintain the perfect functionality of
      the contralateral kidney we decided not to proceed further, but to perform only
      left nephrectomy. During surgery mesocolon laceration occurred, so the patient
      underwent also colic resection. DISCUSSION. Thrombosis secondary to a closed
      renal abdominal trauma is an uncommon event, with little clinical expression. It
      is the consequence of an injury. Deceleration produces arterial dissection, which
      alters the blood flow to the kidney, which is then twisted and complicated with
      renal thrombosis. Quite common is the association with diaphragmatic rupture or
      urethral detachment. The alterations of renal parenchyma in the early hours are
      detectable only through CT scan, which represents the method of election, and
      which can highlight a functionally silent kidney. CONCLUSIONS. Renal thrombosis
      requires that diagnosis is done within the first 12 hours; a rapid
      revascularization should be promptly attempted.

PMID- 21086351
TI  - [A rare case of fibroepithelial polyp of the proximal urethra in a young woman].
AB  - Fibroepithelial polyps are benign epithelial tumours which are rare in adults. In
      females they usually arise from the distal part of the urethra and protrude
      through the external meatus. We report a case of a twenty-seven-year-old woman,
      presenting with painless terminal gross haematuria, affected by a neoplasm
      located in the proximal urethra near the bladder neck. Transurethral resection
      was performed. Endoscopic image of the tumour and histopatological details are
      shown.

PMID- 21086352
TI  - [Angiomyofibroblastoma-like tumors].
AB  - Angiomyofibroblastomas are rare, benign, slow-growing tumors, that occurring
      predominantly in vulvar lesions of premenopausal women. In male patients only few
      cases are reported (angiomyofibroblastoma-like tumors). They occur mostly in
      scrotal and inguinal regions. We report a case of left scrotal
      angiomyofibroblastoma-like tumor in a 52-years old man. After a biopsy for
      histological examination, a complete surgical excision was performed. At 12
      months' follow-up the patient is asymptomatic, and no tumor signs were was found
      on by abdominal computed tomography.

PMID- 21086353
TI  - [Testis tumors: what is new?].
AB  - Germ-cell tumors (GCTs) are extraordinary chemosensitive neoplasms that resemble
      the model for the cure of cancer even in metastatic disease. Nonetheless, a small
      portion of patients does not achieve a long-lasting complete response and new
      efforts are then required in order to further improve their healing rate. This
      paper summarizes what is new about the management of these tumors through
      dedicated sections about biology, prognosis and treatment. Special interest is
      then focused on the Italian reality and how it participates to the advances made
      by the International community.

PMID- 21086354
TI  - [Perception of chronic pelvic pain in women: predictors and clinical
      implications].
AB  - Pain is a complex subjective experience, associated with neurovegetative,
      affective and cognitive rapid changes. Biological, psychosocial and contextual
      factors may contribute. Chronic inflammation, of whatever cause, is the leading
      contributor to chronic pain. The mast cell directs both the inflammatory process
      and the shift to chronic pain, mediating through the production of Nerve Growth
      Factor (NGF) and other neurotrophic molecules. Women, in the fertile age, are
      biologically more vulnerable to chronic inflammation, as fluctuations of
      estrogens are agonist factors of mast cells degranulation, mostly in the
      premenstrual phase. Pain is defined as "nociceptive" when it indicates an ongoing
      damage; "neuropathic" when it becomes a disease per se. Chronic Pelvic Pain (CPP)
      indicates an invalidating, persistent or recurrent pelvic pain, persisting for
      more than 6 months. CPP is the main complaint of 10-15% of gynaecologic
      consultations, leading to 40% of diagnostic laparoscopies and 15% of
      hysterectomies. Comorbidity, i.e. the coexistence of pathologies and painful
      syndromes in different pelvic organs, is another common feature. Cystitis, vulvar
      vestibulitis, endometriosis, irritable bowel syndrome all play an important role
      and contribute to identifying the hyperactive mast cell and related chronic
      inflammation as the common pathophysiologic factor. The paper reviews nociception
      characteristics, the emerging role of mast cells, the pathophysiology of
      comorbidity, biological, psychosexual and contextual predictors, and stresses the
      need to move from a "hyperspecialistic" perspective to a multisystemic reading of
      CPP, with special attention to the urologic perspective.

PMID- 21086355
TI  - [Phytotherapy in urology].
AB  - Complementary and alternative medicine (CAM) includes various practices, measures
      and products which are not presently considered as part of the conventional
      (mainstream) medicine. Herbal products, vitamins, minerals and amino acids are
      increasingly popular as dietary supplements for the treatment, improvement and
      prophylaxis of urological diseases, and as therapeutic options to improve general
      health and well-being. As these products are available for free without
      prescription, conventional healthcare providers are often unaware that their
      patients are using CAM. A particular attention is paid to herbal products by the
      public. For this reason it is essential to know that some herbal supplements may
      act in the same way as chemical drugs, and that the fact that they originate
      'from nature' does not mean that they are safe and/or with no potential harmful
      effects and/or toxicity. The possible interactions with conventional medications
      and contamination with prescription drugs and metals have been reported. The
      active components of many phytotherapeutic preparations and their mechanism(s) of
      action are still being determined and evaluated. There is scientific evidence for
      the effectiveness of some treatments, but for most of them, many important key
      questions still need to be answered through basic research and well-designed
      studies, according to established guidelines. Because of the increasing
      popularity and use of Phytotherapy, urologists should not ignore it, and be well
      informed about its benefits and potential risks.

PMID- 21086356
TI  - Is antibiotic prophylaxis in invasive urodynamics a useful procedure in
      postmenopausal subjects?
AB  - OBJECTIVES. To define the incidence rate of urinary tract infections (UTI) and
      the usefulness of antibiotic prophylaxis in postmenopausal female undergoing
      invasive urodynamics (IU). METHODS. 262 postmenopausal females underwent IU,
      being previously double-blindly randomized in 2 homogenous age-matched groups.
      Group 1 (130 patients) received oral antibiotic prophylaxis with a single 400 mg
      dose of norfloxacin. Group 2 (132 patients) was given placebo. The statistical
      analysis was performed using a Chi-Square test, in order to evaluate any
      difference between groups for UTI incidence rate. RESULTS. 54 patients out of 262
      (20.6%) developed a UTI [24 out of 130 subjects who received antibiotic
      prophylaxis (18.4%), and 30 out of 132 subjects who received placebo (22.7%)]. As
      per the UTI incidence rate, no statically significant difference (p>.05) was
      shown between patients receiving and those not receiving the antibiotic
      prophylaxis. CONCLUSIONS. The UTI incidence rate in postmenopausal women
      undergoing urodynamics is not affected by the administration of antibiotic
      prophylax.

PMID- 21086357
TI  - Calcium and magnesium in male reproductive system and in its secretion.Part II*
      within-subject variability in human seminal plasma and spermatozoa.
AB  - This study was undertaken to find out what, if any, within-subject variability
      exists in semen parameters, and calcium and magnesium levels in seminal plasma
      and spermatozoa. Significant changes (p<0.05) were found in semen volume and in
      the percentage of sluggish motile spermatozoa. No other significant changes were
      seen in semen parameters or in calcium or magnesium in spermatozoa and seminal
      plasma.

PMID- 21086358
TI  - [Efficacy of dutasteride, alfuzosin or both on Quality of Life in patients with
      prostatic hyperplasia and BOO.A two-year spontaneous, observational, self
      controlled study].
AB  - Three homogeneous groups of patients suffering from benign prostatic hypertrophy
      (BPH) were evaluated by means of a two-year observational study, in order to
      assess and compare their Quality of Life (QoL) under the following different
      medical treatments. Group 1: alfuzosin alone, Group 2: alfuzosin and dutasteride,
      Group 3: dutasteride alone. QoL was evaluated by validated indexes, such as the
      IPSS and the QoL-Vas. Although different in entity and timing, as expected, all
      the three groups showed an improvement. The best and quickest results were
      detected in the drug association of Group 2. Significant decrease in volume was
      detected in the dutasteride groups (2 and 3) but not in group 1 (alfuzosin
      alone), where a quick relief of LUTS was detected, due to its wellknown
      alphalytic action. Our results suggest that dutasteride alone does not result in
      a rapid decrease in LUTS, whereas it can help to manage the reduction of the
      prostate volume. A combination therapy seems therefore to be recommended to
      obtain LUTS relief both in the short and long term results.

PMID- 21086359
TI  - [Chronic prostatitis and PSA values].
AB  - OBJECTIVES. There is evidence of a clinical correlation between chronic
      prostatitis and elevated serum levels of prostate specific antigen (PSA). In the
      present study a system was developed to stage inflammation in benign prostate
      hyperplasia (BPH), which correlates with serum PSA. MATERIALS AND METHODS. We
      retrospectively studied 98 patients undergoing transurethral resection of
      prostate. In all patients, histological sections of prostate showed BPH and
      inflammatory cell infiltration, which could be graded as G1, G2 and G3, according
      to involvement of epithelium. PSA levels were assessed pre- and postoperatively
      by the Immulite 2000 PSA assay. RESULTS. The difference in mean serum PSA values
      between groups G1 and G3 was highly significant (G1 = 3.3+/-2.1; G3 = 7.1+/-3.9
      ng/mL; p<0.05). Mean age, prostatic weight and PSA density were similar in the
      three groups (p<0.05). CONCLUSIONS. We concluded that in patients with BPH and
      prostatitis on pathological examination there is an associated PSA elevation when
      glandular epithelium is disrupted.

PMID- 21086360
TI  - [Is phlebography crucial in Tauber varicocele sclerotherapy?].
AB  - OBJECTIVES. Our aim was to discover whether it is possible to eliminate
      retrograde phlebography in the treatment of varicocele by using Tauber procedure.
      METHODS. We treated 102 consecutive left varicocele patients between November
      2003 and May 2007. In 72 patients (Group A) we used the Tauber procedure, without
      performing preliminary retrograde phlebography, and injecting saline solution
      instead of contrast medium; in 30 patients (Group B) we performed the standard
      Tauber procedure. We followed up with scrotal color Doppler Ultrasonography and
      spermograms at 6 months. RESULTS. The patients who underwent the Tauber procedure
      without phlebography (Group A) obtained results similar to those treated with
      phlebography (Group B). With our technique, surgical time and costs are reduced
      and, most importantly, exposure to radiation is avoided. CONCLUSIONS. We believe
      that Tauber procedure for the treatment of varicocele can be performed without
      retrograde phlebography.

PMID- 21086361
TI  - [Synchronous bilateral percutaneous nephrolithotomy (PCNL)].
AB  - BACKGROUND. The management of bilateral renal stones still represents a
      therapeutic challenge and synchronous bilateral percutaneous nephrolithotomy
      (PCNL) appears to be a well tolerated, safe and relatively rapid procedure with a
      favorable cost-benefit ratio. The purpose of the present study is to report our
      experience in the synchronous percutaneous treatment of bilateral renal stones.
      METHODS. We retrospectively evaluated clinical files from 4 consecutive patients
      (BS, BE, OCB, FL), who underwent a synchronous bilateral PCNL, performed by the
      same operator (ZF), for the management of renal persistent and/or recurrent
      stones after extracorporeal shock wave lithotripsy, or other surgical maneuvers.
      From each patient's file we recorded a clinical history, any peri- and post
      operative complication, any therapeutic resolution employed and the outcomes in
      terms of stones persistence/recurrence. RESULTS. Overall, 3 men (BS, BE, FL) and
      1 woman (OCB), their age ranging from 31 up to 76 years, consecutively underwent
      synchronous bilateral PCNL. In 75% of cases a calcium- oxalate nephrolithiasis
      was found. We did not find any peri- or post-operative complication. All patients
      were stone-free after a mean follow-up of 12 months (range: 3-24 months).
      CONCLUSIONS. Synchronous bilateral PCNL is a relatively safe procedure; it may be
      performed in selected patients without increasing the morbidity of this surgical
      maneuver. The simultaneous treatment of the contra-lateral kidney may be taken
      into account only when the PCNL of the first side has been performed quickly and
      easily without any peri-operative complication.

PMID- 21086362
TI  - [Fournier's gangrene: our experience of 10 cases].
AB  - Fournier's gangrene, described for the first time by Alfred Jean Fournier in
      1883, is a very uncommon disease. It is characterized by an acute process of
      cellulites and necrotizing fasciitis of the external genitalia, perineum and
      abdominal wall; its mortality rate is about 30-50%. We retrospectively reviewed
      10 patients affected by Fournier's gangrene admitted to our Department of Urology
      from 1997 to 2006. At a mean follow-up of 37 months (range 0-108) 7 patients are
      alive and disease free, 1 patient is alive bearing the signs of the gangrene, and
      2 patients died because of the disease complications. We have noted that
      patients' survival depends on early intervention and extremely aggressive
      approach. The combination of these factors with antibiotic therapy and supportive
      care have made this disease treatable and curable.

PMID- 21086363
TI  - [Mesothelial cyst of the kidney. A rare case report of this neoformation on the
      left kidney].
AB  - The authors are hereby presenting a rare case of neoformation developing on the
      left kidney in a 80-year-old patient affected by left lumbar backache. The
      neoformation appears doubtful in nature, on ultrasonography, CT scan and MRI. The
      lesion is roundish and contiguous at the kidney convex edge; due to its clinical
      aspects, it requires a surgical management and is, therefore, easily excised. The
      histopathologic examination confirms it is a mesothelial cyst. The case is
      presented for its absolute rarity and for the preoperative diagnostic doubts it
      may generate.

PMID- 21086364
TI  - [Ricordo del professor giorgio ravasini].

PMID- 21086365
TI  - [La classificazione delle neoplasie vescicali: passato e presente].

PMID- 21086366
TI  - [La cistectomia ieri come oggi?].

PMID- 21086367
TI  - [La cistectomia radicale nel paziente anziano: 10 anni di esperienza chirurgica].

PMID- 21086368
TI  - [Surgery for renal carcinoma metastases].
AB  - During the last few years, the increasing use of diagnostic imaging (especially
      ultrasound) has allowed a remarkable rise in the detection of asymptomatic, early
      stage renal neoplasms, possibly treatable by radical surgery. Renal cell
      carcinoma, however, is still the renal neoplastic condition with the highest
      mortality rate, due in most cases to the presence of distal metastases. Because
      of a lack of agreement on an efficient systemic therapeutic approach, surgery is
      generally considered to be the most suitable option to remove metastases: it is
      technically easy to perform, it can increase survival and the patient's
      psychological compliance, though metastasectomy is unlikely to cure the
      metastatic patient. In our experience, we studied 1475 patients who underwent
      surgery for renal cell carcinoma from 1983 on. 304 (20%) developed a metastasis;
      4 subjects only (5.4%) out of the 74 having multiple metastatic anatomical sites
      were long-surviving. 39 subjects (16.9%) out of the 230 having single-site
      metastases are currently disease-free (mean follow-up: 80 months from diagnosis):
      33 out of the 111 patients who underwent metastasectomy, 4 out of the 57 who
      received a medical therapy, 1 out of the 14 being administered radiotherapy, and
      1 out of the 48 who were cared under palliative purposes only. Therefore we
      concluded that, in case of single-site (lung or adrenal) metastases, surgery is
      the most suitable and advisable therapeutic approach, being the only option able
      to achieve survival even for a small amount of patients. New biologic drugs are
      currently under investigation, which can interfere with tumor proliferation and
      angiogenesis: the study results are still preliminary, nevertheless these drugs
      open the way to a multimodal medical option of treatment for metastatic renal
      cell carcinoma.

PMID- 21086369
TI  - [Botulinum toxin in the treatment of overactive bladder].
AB  - Clinical effectiveness of botulinum toxin (BTX) in the treatment of both
      neurogenic and idiopathic detrusor overactivity has been demonstrated in several
      studies. However, different protocols and techniques have been used by authors.
      METHODS. Literature review on intradetrusor injection of BTX for detrusor
      overactivity. RESULTS. The greatest clinical experience reports the use of 200
      and 300 U Botox(r). Available data suggest that clinical efficacy, duration, and
      the side effect profile is similar at these doses. Very few data, on the other
      hand, are available regarding the clinical outcomes using the Dysport(r)
      preparation; isolated reports support that efficacy is similar when using a
      dosing range of 500 to 1000 SU with increased risk of systemic side effects using
      1000 SU. A variety of injection volumes was used, demonstrating similar efficacy
      and tolerability profile. Clinical effect duration extends six to ten months in
      the majority of studies. Data suggest that a repeated injection scheme proves
      successful in the vast majority of initial responders. CONCLUSIONS. Safety,
      effectiveness, specificity and reversibility make BTX a new attractive treatment
      modality for overactive bladder syndrome. However, more experience is needed to
      standardize the injection protocol with respect to therapeutic outcomes and
      adverse effects.

PMID- 21086370
TI  - [Psycho-relational aspects of urinary incontinence in female sexuality].
AB  - Urinary incontinence (UI) is a very common disorder in women, involving severe
      consequences on the patients' perception of quality of life and sexuality. The
      aim of this contribution is to analyze the psycho-relational aspects linked to
      UI, focusing on sexual activity, self-perception of sexual competence and self
      esteem. Urinary incontinence causes feelings of shame and inadequacy as well as
      low self-esteem; it may affect sexual activity, reducing sexual intercourse
      frequency. Many authors highlight a strong comorbidity between urinary
      incontinence and sexual dysfunctions, such as dyspareunia, vaginismus, hypo
      active sexual desire, arousal and orgasm disorders. Literature analysis shows
      that changes in sexual activity are influenced not only by urinary incontinence
      symptoms but also by the disorder self-perception, by previous sexuality,
      menopause, social status and the partner's attitude. The etiological study of
      urinary incontinence shows that several different factors play a role in this
      disorder. Therefore, an integrated therapeutic approach is suggested,
      considering, besides the organic issues, the experience and feelings of patients
      as well as the consequences on their sexual and social life.

PMID- 21086371
TI  - [Clinical evaluation of nuclear matrix protein 22 as urinary marker of
      transitional cell carcinoma of bladder].
AB  - OBJECTIVES. Biomarkers (BTA, NMP22, FDP etc.) have been and continue to be
      evaluated as adjuncts or substitutes for cystoscopy, which is invasive and
      uncomfortable for some patients. Nuclear matrix protein-22 (NMP22) is involved in
      the regulation of nuclear processes. The main objective of the present study is
      to evaluate the clinical utility of urinary NMP22 as a tumor marker in the follow
      up of transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS.
      The study included 62 patients undergoing follow-up, who had had TCC of bladder
      but who were disease-free at the beginning of the study, as confirmed by
      cystoscopy. Urine samples were collected for urinary cytology and NMP22 test
      before the cystoscopy. All samples were processed according to the instructions
      provided with the manufacturer's kit instructions. Results. 12 cases of TCC
      recurrences were detected with biopsy. Cystoscopy was positive in 8 cases, NMP22
      test was positive in 11 cases, and in only one case the cytopathology yielded
      positive results. In 14 cases NMP22 resulted as false positive. CONCLUSIONS.
      Urinary NMP22 appeared to be a potential tumor marker for detecting TCC of the
      bladder, which might rise the sensitivity of cystoscopy especially in high-grade
      cancer surveillance more than cytology might do.

PMID- 21086372
TI  - [Tadalafil versus sildenafil citrate in the treatment of ED:Italian patients'
      preferences and explanatory notes].
AB  - This is an open, multicentre, randomized, crossover study having the aim to
      evaluate the preference for sildenafil citrate or tadalafil in a population of
      Italian patients affected by ED, and to compare the efficacy and safety of these
      two drugs. MATERIAL AND METHODS. From October 2003 to November 2004, thirteen
      Italian centers enrolled ED patients (age >18) being in steady and naive relation
      to ED treatment, both through PDE5 inhibitors and any other treatment option.
      These patients were randomized to sildenafil or tadalafil for 12 weeks, after
      which they were switched to the alternative treatment for a further 12 weeks. The
      preference was evaluated through the Treatment Preference Question (TPQ): "During
      this clinical trial you have taken tadalafil and sildenafil for the treatment of
      erectile dysfunction. Which medication do you prefer to take for the next 8 weeks
      of treatment?". Moreover, patients were asked to express their preference as
      "strong" or "moderate" and to answer some questions to clarify the reasons behind
      their preference. SEP and IIEF-EF questionnaires were used for a comparison of
      efficacy. RESULTS. 167 patients were enrolled, 144 of whom completed both
      treatment periods. On being asked the TPQ, 75% of patients (n=108) decided to
      continue treatment with tadalafil, in particular because it made it possible to
      have an erection many hours after taking the medication (first or second
      preference reason for 64.8% of patients), while 25% (n=36) preferred sildenafil
      (p=0.001). Both drugs improved the IIEF-EF and SEP scores compared to baseline,
      with a slightly but significantly greater improvement with tadalafil for both
      parameters. CONCLUSIONS. Tadalafil and sildenafil are both effective and well
      tolerated. Most of the patients prefer tadalafil thanks to the possibility of
      having sexual intercourse many hours after taking the medication.

PMID- 21086373
TI  - Effects of surgery, medical therapy and combined therapeutical approach on
      spermatogenesis in patients suffering from varicocele: a prospective and
      comparative analysis.
AB  - The definite mechanisms through which varicocele affects spermatogenesis are
      still not completely understood, and consequently the exact role of the various
      approaches available for its treatment is still under debate. In this study a
      comparison of medical treatment, surgery and combined approach is reported.
      MATERIAL AND METHODS. The study was conducted as a prospective evaluation of 189
      patients suffering from varicocele and oligoasthenospermia. Patients were
      randomized in three groups on the basis of the different therapeutic approach:
      group A, treated only with varicocelectomy; group B, treated with varicocelectomy
      associated with hormonal therapy; group C, treated only with hormonal therapy.
      Randomization criteria were based on patient's preference. Spermiogram tests were
      carried out at baseline and after 3, 6 and 12 months from therapy. RESULTS. Our
      results show that patients undergoing a combined therapeutical approach (surgery
      associated with hormonal therapy) and medical therapy alone achieve a greater
      improvement of seminal parameters than patients treated by surgery only.
      CONCLUSION. Data reported in this study are in accordance with Literature review.
      Furthermore, the association between varicocelectomy and early use of hormonal
      therapy seems to improve testis functional rehabilitation with a early evidence
      of sperm parameters improvement. In the light of these results of ours, we should
      conclude that surgical treatment is not effective for the spermatogenesis
      improvement.

PMID- 21086374
TI  - Vesico-sphincter dysfunctions in Pure Cerebellar Syndrome (PCS): a possible basis
      for the study of anatomo-functional correlations.
AB  - The neurological polymorphism of Pure Cerebellar Syndromes (not including the
      heredodegenerative patterns) led the Authors to try to verify the possible
      correlations between neurological damages and urodynamic findings. MATERIAL AND
      METHODS. From 2001 to 2006 thirty patients affected by PCS were studied. They
      underwent several neurological and urological investigations, including
      videourodynamics. RESULTS. Sixteen cases (76%) showed urinary incontinence due to
      non-inhibited detrusor contractions, with no evidence of vesico-sphincter
      dyssynergia; the remaining patients showed a moderate degree of incoordination.
      CONCLUSIONS. The authors highlight the basic role of cerebellum in modulating the
      motor activities and the coordination of the bladder-sphincter structures, also
      in the light of the outcomes gathered in these patients, who were not suffering
      from other superior structure deficiencies.

PMID- 21086375
TI  - [Urologic surgical procedures in patients with uterus neoplasm and colon-rectal
      cancer].
AB  - INTRODUCTION. During the last 30 years, the multidisciplinary treatments of colon
      and uterus neoplasm have yielded an increase in total survival rates, fostering
      therefore the increase of cases with regional relapse involving the urinary
      tract. In these cases the iterative surgery can be performed, if no disease
      secondary to pelvic pain, haemostatic or debulking procedure is present, and must
      be considered and discussed with the patient, according to his/her general
      status. MATERIALS AND METHODS. From 1997 to August 2007 we performed altogether
      43 pelvic iterative surgeries, with simultaneous urologic surgical procedure
      because of pelvic tumor relapse in patients with uterus neoplasm and colon and
      rectal cancer. In 4 cases of anal cancer, the urological procedure were: one
      radical prostatectomy with continent vesicostomy in the first case, while in the
      other 3 cases radical pelvectomy with double-barrelled uretero-cutaneostomy. In
      23 cases of colon cancer, the urologic procedures were: 9 cases of radical
      cystectomy with double-barrelled uretero-cutaneostomy, 4 cases of radical
      cystectomy with uretero-ileo-cutaneostomy according to Bricker- Wallace II
      procedure, and 9 cases of partial cystectomy with pelvic ureterectomy and
      ureterocystoneostomy according to Lich-Gregoire technique (7 cases) and Lembo
      Boari (2 cases) procedure. In 16 cases of uterus cancer, the urological procedure
      were: 7 cases of partial cystectomy with pelvic ureterectomy and uretero
      cystoneostomy according to Lich-Gregoire procedure; in 3 cases, a radical
      cystectomy with urinary continent cutaneous diversion according to the Ileal T
      pouch procedure; 2 cases of total pelvectomy and double uretero-cutaneostomy, and
      4 cases of bilateral uretero-cutaneostomy. RESULTS. No patients died in the
      perioperative time; early systemic complications were: 2 esophageal candidiasis,
      1 case of venous thrombosis. CONCLUSIONS. The iterative pelvic surgery in the
      case of oncological relapse involving the urinary tract aims to achieve the best
      quality of life with the utmost oncological radicality. The equation: eradication
      of pelvic neoplasm and urinary tract reconstruction, with acceptable quality of
      life, will be the future target; nevertheless, it is not possible to establish
      guidelines beforehand, and the therapy must be adapted to each single case.

PMID- 21086376
TI  - [Use of human fibrinogen and human thrombin for urethral reconstructive surgery].
AB  - The objective of the present study is to test the use of a haemostatic sponge for
      urethral reconstructive surgery and to assess the relevant benefits. METHODS. The
      haemostatic sponge is made up of collagen with human fibrinogen and human
      thrombin. When the sponge gets in contact with fluids, such as blood, lymph or
      saline solution, the fibrinogen and thrombin are activated and form a fibrin net
      able to achieve local haemostasis and tissue regeneration. This kind of product
      was used in 30 selected patients (pts.), aged 19 - 70 (mean age: 35), who
      underwent single-stage anastomotic urethroplasty from January 2006 to March 2007:
      22 bulbar end-to-end anastomoses and 8 bulbo- prostatic anastomoses. All
      operations were performed due to post-traumatic stricture of bulbar and posterior
      urethra. The main selection criterion for the use of the haemostatic sponge has
      always been the tendency to and/or the presence of bleeding in the different
      surgical stages. The sponge imbibed in saline solution and suitably modeled for
      all specific requirements was differently placed: sleeve-shaped in the case of
      bulbar anastomoses (16 pts.); as a "patch" in the centre of spongioplasty in
      bulbo-prostatic anastomoses (8 pts.), and within the widening incisions of the
      urethral roof performed between the two cavernous bodies at level of the
      intercrural septum (5 pts.). In 1 case (obese patient) a single sponge was placed
      after the deep perineal reconstruction on the bulbo-cavernous muscle-
      subcutaneous layers because of massive bleeding. RESULTS. In all cases a perfect
      control of haemostasis could be achieved, with immediate end of bleeding in the
      points where the haemostatic sponges were used. The dressings performed on day 3
      upon removal of the compressive scrotum-perineal bandages did not show any late
      post-operative bleeding. The follow-up visits at month 1 and 3 yielded positive
      outcomes for all 30 patients, who achieved complete wound healing by first
      intention, and a perfect anastomosis especially in the bulbar end-to-end
      urethroplasty, confirmed by urethrografy at one month. CONCLUSIONS. The
      association of human fibrinogen and human thrombin in haemostatic sponges
      represents a manageable, useful product, apparently sure, not negatively
      interfering in repairing and regenerating tissue processes, and allowing a simple
      and direct control of important bleeding events occurring during urethral
      reconstructive surgery as well as other operations. It is therefore advisable to
      more widely use the product after a suitable followup period.

PMID- 21086377
TI  - [Angiomyofibroblastoma of the spermatic funiculus. A case report of this lesion
      of the spermatic funiculus].
AB  - The authors are hereby presenting a rare case of angiomyofibroblastoma of the
      funiculus in a 20-year-old patient, having a non-aching tumefaction at the left
      region of the scrotum. This tumefaction was solid and non homogeneous, both on
      ultrasonography and MRI, of about 5cm in diameter, fully separated from the
      testicle. The markers were all negative. We proceeded with surgical treatment of
      the neoformation. It is mandatory to include this lesion within the differential
      diagnosis of testicle masses. The case is presented for its absolute
      histopathologic rarity and for the difficulty in diagnosis.

PMID- 21086378
TI  - [Neuroendocrine bladder cancer: oncological emergency?].
AB  - Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of
      0.5%- 0.7%. In bladder cancers there is no evident connection between the
      neuroendocrine phenotypic expression and the clinical history. However, prognosis
      is usually poor and the survival rate at 5 years does not exceed 8%, if
      untreated. METHODS. We are here describing three case reports of bladder
      carcinoma with neuroendocrine differentiation, which is extremely aggressive and
      leads rapidly to death. At the present time, the local control of these tumors is
      achieved by radical cystectomy and radiotherapy; they can be both associated to
      chemotherapy. However, since these lesions are fairly rare, there is no gold
      standard therapy and there are no prospective studies on the management of these
      tumors. CONCLUSIONS. Considering the quick evolution and progression of any
      variant of the neuroendocrine tumors of the bladder, urologists and anesthetists
      should see them as real oncological emergencies. A prompt intervention through
      radical surgery with cystectomy and linfadenectomia, and the anathomo
      pathologist's systematic investigation of the scraps could make the approach
      therapeutic and not only palliative. Prospective studies on neo-adjuvant
      chemotherapy as well as experimental studies about target therapies may yield new
      guidelines on the tumor management.

PMID- 21086379
TI  - [Male to female transsexualism].
AB  - The transsexual is a person who suffers from a deep identity disturbance caused
      by physical characteristics which do not correspond to mental traits and
      tendencies. The persistent sense of contradiction between his or her deceptive
      sexual appearance and his or her inner perception, causes a strong desire to
      achieve harmonization of the two. This aspiration, even if modification of
      chromosomal sex is impossible, can be fulfilled by undergoing SRS (Sex
      Reassignment Surgery). SRS represents the last major step of a clinical,
      therapeutic and diagnostic program involving skilled professionals in the
      physical and psychological sciences. Their assistance and counseling helps the
      patient to calmly and consciously decide to undergo SRS. A surgeon has the
      obligation not only to validate the operation outcome, but to also to maintain a
      long-term follow-up. A transsexual is not just like any other person; he or she
      should therefore be treated with sympathy and understanding. The surgeon should
      try his best to establish a relationship of mutual trust, taking into account the
      causes of anxiety and stress felt by the patient, and keeping in mind the
      ultimate objective, which is an improvement in the quality of life. At present,
      the most widely used surgical techniques are the Simple Penile Skin Inversion,
      the Penile-scrotal flap Inversion and the enterovaginoplasty. Each surgical
      technique has its own advantages and disadvantages, and it is up to the surgeon,
      in discussion with the patient, to make the appropriate choice. The surgical
      technique performing the Simple Penile Skin Inversion seems to ensure a better
      cosmetic appearance and an adequate lubrication, but a lower rate of
      satisfaction, in relation to the neocavity depth. On the contrary, the Penile
      Scrotal Flap Inversion guarantees an adequate vaginal depth and lubrication, even
      though the cosmetic appearance is not always completely satisfactory. In our
      experience, a significant number of patients were satisfied with the chosen
      surgery and felt comfortable with their new post-operative gender. Taking into
      account all the complications involved, none of the patients did regret;
      actually, they would recommend the same operation to others. The overall results
      of some studies carried out on patient satisfaction before and after SRS show a
      marked post-surgery improvement of sexual life.

PMID- 21086380
TI  - [Regenerative medicine: applications and development in urology].
AB  - PURPOSE. Congenital abnormalities and acquired disorders can lead to organ damage
      and loss. Nowadays, transplantation represents the only effective treatment
      option. However, there is a marked decrease in the number of organ donors, which
      is even yearly worsening due to the population aging. The regenerative medicine
      represents a realistic option that allows to restore and maintain the normal
      functions of tissues and organs. This article reviews the principles of
      regenerative medicine and the recent advances with regard to its application to
      the genitourinary tract. RECENT FINDINGS. The field of regenerative medicine
      involves different areas of technology, such as tissue engineering, stem cells
      and cloning. Tissue engineering involves the field of cell transplantation,
      materials science and engineering in order to create functional replacement
      tissues. Stem cells and cloning permit the extraction of pluripotent, embryonic
      stem cells offering a potentially limitless source of cells for tissue
      engineering applications. Most current strategies for tissue engineering depend
      upon a sample of autologous cells from the patient's diseased organ. Biopsies
      from patients with extensive end-stage organ failure, however, may not yield
      enough normal cells. In these situations, stem cells are envisaged as being an
      alternative source. Stem cells can be derived from discarded human embryos (human
      embryonic stem cells), from fetal tissue or from adult sources (bone marrow, fat,
      skin). Therapeutic cloning offers a potentially limitless source of cells for
      tissue engineering applications. Regenerative medicine and tissue engineering
      scientists have increasingly applied the principles of cell transplantation,
      materials science and bioengineering to construct biological substitutes that
      will restore and maintain normal function in urological diseased and injured
      tissues such as kidney, ureter, bladder, urethra and penis. CONCLUSIONS.
      Regenerative medicine offers several applications in acquired and congenital
      genito-urinary diseases. Tissue engineering, stem cells and, mostly, cloning have
      been applied in experimental studies with excellent results. Few preliminary
      human applications have been developed with promising results.

PMID- 21086381
TI  - [Balanitis xerotica obliterans].
AB  - Balanitis xerotica obliterans (BXO), first described by Stuhmer in 1928, is a
      chronic, progressive, atrophic, sclerosing process involving prepuce, glans and
      urethra. Its aetiology is unknown. After a short terminological excursus and a
      review of the aetiological hypothesis, we have focused on BXO in daily urological
      practice. We are here describing the clinical presentation and its differential
      diagnosis with premalignant and malignant lesions of the penis. We tried to
      define the relationship between BXO and squamous cell carcinoma of the penis.
      Particular attention was then cast on urethral stenosis. Finally, we focused on
      the treatment of BXO: corticosteroid local therapy as first line treatment or as
      adjuvant therapy after circumcision, surgical therapy including circumcision,
      laser therapy of the glans lesions, meatoplasty in the stenosis of the anterior
      urethra. We also stressed the need for histological examination of the preputial
      specimen for a correct follow-up and for medicolegal reasons.

PMID- 21086382
TI  - [Endourological management of ureteral stenosis and vesicoureteral reflux after
      renal transplantation].
AB  - INTRODUCTION AND OBJECTIVES. Ureteral stenosis and vesicocoureteral reflux after
      renal transplantation represent a key concern because of their incidence and the
      associated morbidity. Prompt diagnosis and minimally invasive treatment are
      mandatory in immunosuppressed patients with single kidney. The aim of this study
      is to evaluate the success rate of the endourological techniques in the
      management of such complications. MATERIALS AND METHODS. Between January 1996 and
      December 2006, 647 kidney transplants were performed. Urinary tract continuity
      was re-established by ureteroneocystostomy according to Gregoir-Lich technique.
      We observed 13 cases of ureteral stenosis (2%) and 11 cases of symptomatic
      vesicoureteric reflux (1.7%). The endourogical procedure was performed in 13
      patients: 5 cases of II-III grade vesicoureteric reflux, 4 early ureteral
      stenosis and 4 late ureteral stenosis. Patients with vesicoureteric reflux
      underwent endoscopic injection of macroplastique in 4 cases and Durasphere in 1.
      Early ureteral stenoses were treated using balloon dilation in 2 cases, balloon
      dilation and laser endoureterotomy in 3, ureteral stent placement in the other.
      Recipients with late stenosis underwent laser incision and balloon dilation in 2
      cases, balloon dilation in 1 and a laser incision only in the last case. Combined
      antegrade and retrograde endoscopic approach was performed in 7 patients, whereas
      retrograde access in 1. RESULTS. Endourologic treatment was successful in 9 cases
      (69.2%); 2 patients required open reconstructive surgery due to endourological
      technique failure (early ureteropelvic junction stricture, late ureterovesical
      anastomotic stricture). Vesicoureteric reflux was corrected in 3 patients (60%),
      2 patients underwent uretero-ureterostomy for recurrent reflux. No technique
      related morbidity was observed. With a mean follow- up of 81.6 months, 8 patients
      show normal renal function, 5 patients have returned to haemodialysis (4 for
      chronic rejection, 1 for carcinoma in the graft). CONCLUSIONS. Considering their
      low morbidity and the satisfactory success rate, we claim that endourological
      procedures should be considered the preferred treatment for ureteral stenosis and
      vesicoureteric reflux in selected patients.

PMID- 21086383
TI  - [Amikacin: a novel modulator of vesical and prostate efferences. An in vitro
      experimental study].
AB  - The autonomic efferent neurotransmission to the bladder and prostate smooth
      muscle is a potential target for drug therapy of specific low urinary tract
      disfunction (LUTD). Since amikacin and other amynoglicosides were reported to
      affect neurotransmission by a pre-junctional mechanism, we investigated the
      effect of amikacin on isolated rat and human detrusor smooth muscle contraction
      and on isolated rat and human prostate contraction, to further evaluate its
      potential relaxant properties. MATERIALS AND METHODS. Samples of detrusor smooth
      muscle and prostate tissue, obtained from 97 rats and 16 patients undergoing
      surgery, were studied through the measurement of isometric contraction induced by
      electrical field stimulation (EFS) and other pharmacological stimuli in the
      presence or absence of 1mM amikacin in a low-Ca medium. RESULTS. Amikacin 1 mM
      significantly reduced contraction of isolated rat and human detrusor muscle and
      prostate, achieved with pre-junctional stimulation, while no significant effect
      was observed on contraction induced by pharmacological post-junctional
      stimulators. EFS contraction inhibited by amikacin was restored after addition of
      calcium chloride. The amikacin effect was comparable to the effect of magnesium
      ions, which are known to exert a pre-junctional inhibition of neurotransmitter
      release. CONCLUSIONS. Amikacin significantly inhibited rat and human detrusor and
      prostate contraction evoked by pre-junctional stimulation in vitro, suggesting a
      depressant effect on autonomic efferent neurotransmission. Further
      pharmacokinetics studies and researches on related compounds may hold potential
      for future development in the treatment of specific low urinary tract disfunction
      (LUTD).

PMID- 21086384
TI  - Enterovesical fistulas secondary to Crohn's disease:medical versus surgical
      therapies.
AB  - The purpose of this study is to evaluate the efficacy of medical therapies,
      especially infliximab, to induce remission of enteric fistulas in Crohn's disease
      (CD). Similarly to CD, chronic transmural inflammation of the bowel,
      diverticulitis and other pathologies may predispose to the development of
      fistulas. The risk of fistulization secondary to CD ranges from 17% to 80%. We
      focused on enterovesical fistulas, which statistically represent 10% of all
      fistulas secondary to CD. MATERIAL AND METHODS. In this study we decided to
      implement a therapeutic program with infliximab 5 mg/kg associated with steroids,
      which proved to be the most effective method of treatment. From January 2003 to
      March 2005, we studied 4 patients with CD and enterovesical fistulas. All
      patients underwent NMR, colonoscopy and cystoscopy combined with fistulography; a
      therapeutic strategy with cortisone, mesalazine, nutritional therapy and
      infliximab was established. RESULTS. No regression was observed; therefore, all
      the four patients underwent surgery with complete remission of symptoms.
      CONCLUSIONS. Data reported in literature and the evidence from our experience
      seem to be contradictory; we concluded therefore that it is mandatory to consider
      different therapeutic approaches, according to the fistulizing pathways, to such
      a complex disease, and to formulate some hypothesis that might explain why this
      treatment was unsuccessful in our patients.

PMID- 21086385
TI  - History and evolution of dorsal onlay urethroplasty for bulbar urethral stricture
      repair using skin or buccal mucosal grafts.
AB  - OBJECTIVES. To illustrate the history and the evolution over time of bulbar
      dorsal onlay urethroplasty, comparing outcomes when using buccal mucosa or skin
      grafts. MATERIALS AND METHODS. Ninety-four patients underwent bulbar urethral
      reconstruction using two dorsal onlay techniques, namely augmented anastomotic
      urethroplasty and dorsal onlay graft urethroplasty. Preoperative evaluation
      included clinical history, physical examination, urine culture, residual urine
      measurement, uroflowmetry and urethrography. Thirty-four patients underwent
      augmented anastomotic urethroplasty using penile skin (10 cases) or buccal mucosa
      (24 cases) grafts. Sixty patients underwent dorsal onlay graft urethroplasty
      using penile skin (38 cases) or buccal mucosa (22 cases) grafts. Forty-eight out
      of 94 patients received skin grafts and 46 buccal mucosal grafts. RESULTS. Sixty
      four (68%) out of 94 cases were successful, whereas 30 (32%) failed. The 34
      augmented anastomotic urethroplasties provided successful outcomes in 24 cases
      (70.6%), but poor outcomes in 10 (29.4%) cases. The 60 dorsal onlay graft
      urethroplasty proved to be successful in 42 cases (70%), failing in 18 (30%)
      cases. Twenty-eight (58.3%) out of 48 penile skin grafts were successful and 20
      (41.7%) failed. Thirty-six (78.3%) out of 46 buccal mucosa grafts were successful
      and 10 (21.7%) failed. The 30 failed cases were then treated with internal
      urethrotomy in 14 cases (46.7%), perineal urethrostomy in 8 cases (26.7%), two
      stage repair in 4 cases (13.3%), and one-stage repair in 4 cases (13.3%).
      CONCLUSIONS. The dorsal onlay technique used for bulbar urethral stricture repair
      has changed over time. In our experience, the buccal mucosa seems to be the best
      substitute graft material for bulbar urethroplasty using dorsal approach.

PMID- 21086386
TI  - Evaluation of the female sexual function after vaginal surgery using the FSFI
      (Female Sexual Function Index).
AB  - Urinary Incontinence (UI) and Pelvic Organ Prolapse (POP) have a detrimental
      effect on Female Sexual Function (FSF). We decided to focus on the effect of
      vaginal surgery for UI and/or POP on FSF. MATERIALS AND METHODS. 72 women (aged
      42-80, mean age: 62) were given the FSFI questionnaire after undergoing the
      following operations: 54 Tension-Free Vaginal Slings (TFVS), 12 Kelly plications,
      3 hysterectomies+Kelly, 2 Tension-Free Vaginal Slings+Kelly, 1 hysterectomy+
      Kelly+posterior IVS. RESULTS. 35 women did not answer the questionnaire, 6 women
      were sexually inactive and answered only partially; 31 patients answered
      completely. Mean pre- and postoperative scores were, respectively, 25.26 and
      25.22 (normal >26.55). 9 patients had a normal preoperative score, whereas 22 a
      pathological score. The FSFI score did not change postoperatively in 26 women; it
      worsened in 3 and improved in 2 women treated because of coital incontinence.
      CONCLUSIONS. Vaginal surgery for UI and/or POP does not seem to affect FSF in the
      great majority of cases; conditions may worsen or improve, the latter definitely
      resulting from the treatment of Coital Incontinence. The high number of patients
      not answering the questionnaire deserves further studies and it could be - at
      least partially - explained on the basis of psychological and/or cultural
      problems regarding the highly emotional issues of sex, incontinence and prolapse.

PMID- 21086387
TI  - Periorbital emphysema after laparoscopic nephrectomy: case report and literature
      review.
AB  - A 40-year-old lady presented with marked swelling and inability to open her left
      eye immediately after laparoscopic nephrectomy for a left pyelonephritic kidney.
      A diagnosis of periorbital emphysema was made and within 7 days the emphysema
      spontaneously disappeared. Periorbital emphysema is a rare benign condition that
      may complicate a laparoscopic nephrectomy.

PMID- 21086388
TI  - [Phytotherapy and diet for andrological pathologies].

PMID- 21086389
TI  - [Notes on the tumorigenesis of bladder urothelioma].
AB  - Bladder urothelioma is a common and increasingly frequent tumor, which most of
      the times involves initially the bladder mucosa only. Urotheliomas can be
      superficial, with low malignant potential despite their high relapsing activity,
      and highly aggressive ab initio. A series of events are known to influence
      urothelioma genesis, growth, cell interactions and apoptosis. Some initial
      constant changes involving chromosome 9 occur in the urothelium, whereas the 20
      30 % of cases also show an alteration on chromosome 20, which is likely to result
      in marked biological aggressiveness. The transformation of normal urothelium into
      hyperplastic, and then neoplastic, urothelium is secondary to a wide range of
      molecular changes, which are here summarized.

PMID- 21086390
TI  - [Innovations in superficial bladder cancer treatments].
AB  - Bladder cancer treatment is a challenge for both urologists and oncologists.
      Particularly during these last years many changes have been made in the
      management of superficial bladder cancer. In the case of superficial bladder
      cancer, intravesical instillation of chemo/immunotherapeutic agents after
      transurethral resection is the standard. The treatment goals include: complete
      removal of the initial tumor, prevention of recurrences and inhibition of disease
      progression. This work aims at reviewing the new developments in the therapeutic
      field of superficial bladder cancer. A growing trend involves the use of
      multimodality treatment to obtain the activation of the host immunity against the
      tumor, and to enhance the cytotoxic effects of chemotherapeutic agents. The new
      therapeutic modalities, which are under preclinical and clinical investigations,
      are showing promising results.

PMID- 21086391
TI  - [Peyronie's disease: state of the art and future perspectives].
AB  - Peyronie's disease (PD) is characterized by the onset of a fibrous plaque within
      the tunica albuginea of the penile corpora cavernosa, resulting in pain and
      bending during the erection, which can make the intercourse difficult or
      impossible. Evidence from literature supports the autoimmune etiology of PD, and
      suggests genetic and familiar conditions, penile traumatisms and history of
      genital tract diseases as risk factors, even though no definitive conclusions
      arise about the pathogenesis of the disease. Few randomized trials demonstrated
      that medical therapies, such as Vitamin E, Colchicine, Potassium amminobenzoate,
      Tamoxifen and injection therapy with Verapamil are effective in stabilizing the
      acute phase of the disease. Extracorporeal shock wave therapy (ESWT) and
      ionophoresis cannot be considered as first line or gold standard therapies.
      Satisfactory results have been published about Nesbit operation in large number
      of cases with low-stage disease, whereas plication procedures have shown
      significant rates of relapse. High incidence of long-term penile retraction have
      been reported in high-stage disease treated with plaque incision and simple graft
      insertion. Malleable, soft or inflatable prostheses combined with graft implant
      have given the best results in terms of penile straightening and lengthening and
      patients' satisfaction. In conclusion, the PD etiopathogenesis hasn't been
      clearly understood-yet, no medical therapy is fully effective; surgery remains
      therefore the gold standard in case of severe deformity and/or erectile
      dysfunction.

PMID- 21086392
TI  - [Ureterorenoscopy with a flexible instrument].
AB  - Flexible ureterorenoscopy should be routinely used at the Urological Centers that
      deal with urinary stones. Flexible instruments should be used for both diagnostic
      and therapeutic purposes, allowing a safe exploration of the whole upper urinary
      tract. Thanks to their flexibility and to the active and passive deflection of
      their distal part, these instruments allowed to successfully treat several
      difficult situations, such as renal caliceal calculi in the lower calices or even
      in some middle/upper calices or in horseshoe kidneys. The therapeutic potential
      of this approach is enhanced by the large availability of ancillary
      instrumentation, such as baskets, grasps, holmium laser fibers, etc, which is
      continuously growing. On the other side, a steep learning curve of the technique
      is usually required for the surgeon. Furthermore, the intrinsic fragility of the
      instrument components and a potentially lower quality, when compared to that of
      the rigid and semi-rigid ureteroscopes, should be considered.

PMID- 21086393
TI  - [Ligation of the native ureter in kidney transplant].
AB  - The urinary tract reconstruction in renal transplantation is usually performed by
      a ureterocystoneostomy according to Gregoire-Lich technique. In selected
      patients, native ureteral ligation with nephrectomy was done when end-to-end
      anastomosis for ureteroureterostomy was performed. Recently, some Authors have
      proposed the ligation of the native ureter without nephrectomy. We report our
      experience in the ligation of the native ureter with no associated nephrectomy.
      MATERIALS AND METHODS. In 978 renal transplantations performed from April 1986
      through December 2006, we evaluated 68 recipients (69.5%) who underwent ureteral
      ligation without nephrectomy. Mean diuresis was 314 cc/day (range 0-1200 cc/day).
      Follow-up was 1 to 187 months. RESULTS. Only one patient (1.5%) required native
      nephrectomy for fever and abdominal pain. None of the other patients showed
      infections involving native kidney or flank pain during the follow-up. DISCUSSION
      AND CONCLUSION. Our experience confirms the safety and feasibility of native
      ureter ligation without omolateral nephrectomy. Nephrectomy is indicated in the
      case of coexistent intrinsic renal disease, such as non-treatable nephrovascular
      hypertension, symptomatic polycystic kidney disease, chronic renal infection.

PMID- 21086394
TI  - A four-year experience with Holmium-YAG laser:parameters of use.
AB  - In the last years, laser has gained increasingly high popularity in Endourology.
      The newer generation Ho-YAG lasers represent the most updated laser used in
      Urology, being able to successfully treat both urinary stones and soft tissue
      lesions. The aim of this work was to report a multicentre 4-year experience using
      the Ho-YAG laser in the treatment of stones and soft tissue lesions, in order to
      offer parameters and modalities of use in several different situations. MATERIALS
      AND METHODS. Two urological Centers were asked between 2002 and 2005 to use
      Coherent Versa Pulse 20 Ho-YAG laser source in the treatment of urinary stones in
      212 patients, and urinary soft tissue lesions (urethra, ureter or bladder neck
      strictures or urinary tract tumors) in 56 patients. According to the various
      situations (either stone fragmentation or treatment of soft tissue lesions),
      pulse frequency and energy per impulse were differently dosed and set. RESULTS.
      The following parameters were identified as the starting points for the correct
      use of the Ho-YAG laser: a) lithotripsy with rigid endoscope: 365 MUm fiber, 0.8 
      1.2 Joule (J) energy and 6-8 Hz frequency; 365 MUm fiber, 0.8-1.2 J energy and
      10-12 Hz frequency; 550 MUm fiber, 1.0-1.5 J energy and 10-12 Hz frequency. b)
      lithotripsy with flexible endoscope: 270 MUm fiber, 0.6-1.0 J energy and 6-10 Hz
      frequency. c) soft tissue resection in case of: c1) ureteral stricture, 365 MUm
      fiber, 0.6 J energy and 14-16 Hz frequency; c2) urethral stricture, 365 MUm
      fiber, 0.7 J energy and 16-18 Hz frequency; c3) upper urinary tract tumors, 365
      MUm fiber, 0.7 J energy and 16 Hz frequency; c4) bladder tumors 365 MUm fiber,
      0.8 J energy and 16-20 Hz frequency; c5) bladder neck strictures, 365 MUm fiber,
      1.0 J energy and 16-18 Hz frequency. CONCLUSIONS. In the light of these
      parameters, Ho-YAG laser is a very handy instrument for the treatment of both
      urinary stones and soft tissue lesions, which allows to put aside the current
      tools used for the same purposes.

PMID- 21086395
TI  - [The use of bipolar PlasmaKinetic resectoscope in endoscopic resection of the
      prostate: our experience].
AB  - Prostatic endoscopic resection (TURP) is a reference method in the treatment of
      prostatic obstruction. In the past decades, the method used a monopolar
      resectoscope. In the last years, various technologies have been studied to
      improve the efficacy of endoscopic resection. As per our experience, we have
      thence ascertained the variations of the hematic crasis and of the mictional
      asset in TURP patients treated with bipolar knives. 20 patients underwent bipolar
      plasmakinetic resection of the prostate. Their age ranged between 58 yrs and 82
      yrs (av.: 70.2 yrs), the adenoma volume, checked with TR ultrasound scanning, was
      between 33 and 44 cc (av.: 37.6), the Qmax was between 6.4 and 9.0 mL/min (av.:
      7.42 mL/min). A 24Ch resectoscope and spinal anesthesia were used. Bleeding
      during resection was never relevant; therefore resection never had to be stopped.
      After about 36 hours from surgery, the patients' sanguification was checked
      again: a 6.53% reduction of the number of erythrocytes, compared to pre-surgery
      data, was observed, together with a 6.73% decrease of hemoglobin concentration,
      and a 6.3% decrease of hematocrit. Continuous irrigation was suspended during the
      first day, catheter was removed on the 48th hour in 15 cases, and on the 72nd in
      5 cases: the patients were discharged on day 3 in 16 cases, and on day 4 in 4
      cases. A flux evaluation was performed after 3 months, which showed a Qmax
      between 16.6 and 24 mL/min (av.: 19.11), with a significant increase in the
      maximum flow rate. The use of the new technologies in prostatic endoscopic
      resection has allowed us to improve the efficacy of such a method. Above all, the
      use of a bipolar electrosurgical knife enables us to associate a basal hemostasis
      with the resection of the prostatic tissue. Thus, the hematic loss is low, as we
      have been able to ascertain also in our own experience. This gave us the
      possibility to quickly stop continuous irrigation and to early remove the
      catheter. This way, hospitalization was sensibly reduced (av. 76.8 hours). The
      maximum flow rate, in the short term, has been good. We have been able, in our
      experience, to assess that this technology represents a useful guarantee to
      improve the results of prostatic endoscopic resection.

PMID- 21086396
TI  - [Laparoscopic transperitoneal radical prostatectomy:surgical technique. A
      personal experience].
AB  - At present, radical prostatectomy is the standard of care for localized prostate
      cancer. Several mini-invasive urological procedures have been developed during
      the last years, such as the laparoscopic radical prostatectomy, which is nowadays
      an innovative technique for urologists. This procedure shows many benefits in
      terms of anatomic accuracy, reduction of hospitalization and transurethral
      catheterization, recovery of urinary continence and sexual potency. In this study
      we have described the laparoscopic radical prostatectomy technique which is
      carried out by urologists at the "Hopital Henry Mondor" - Creteil, Paris, where
      the first author has worked for six months.

PMID- 21086398
TI  - [Fraley's syndrome. A nephron-sparing laparoscopic surgical procedure. Case
      report].
AB  - 16-year-old girl with Fraley's syndrome, which caused right flank pain and
      urinary infection. The radiologic exam showed a distended calyx and an
      infundibular obstruction caused by compression of normal renal vessels.
      Retroperitoneal laparoscopic calycectomy and closure of infundibulum with calyx
      exclusion were performed.

PMID- 21086397
TI  - [Nephron-sparing surgery versus radical nephrectomy in the treatment of renal
      cell carcinoma up to 7 cm].
AB  - To compare the oncological outcome of nephron-sparing surgery versus radical
      nephrectomy in renal cell carcinoma up to 7 cm by retrospectively reviewing our
      surgical experience. MATERIALS AND METHODS. Data collected from 1290 consecutive
      patients, who underwent surgery for renal carcinoma, have been stored since 1983
      into a dedicated database. The cases with unilateral carcinoma up to 7 cm,
      pT1a/pT1b/pT3a N0/Nx M0, followed up for a minimum of 12 months if disease-free
      were reviewed. RESULTS. 732 patients were selected (mean follow-up: 72 months);
      329 had a tumor less than 4 cm in diameter (182 cases of nephron-sparing surgery,
      147 cases of nephrectomy), while for 403 of them the tumor was 4 cm or more (57
      cases of nephron-sparing surgery, 346 cases of nephrectomy). The comparison
      between tumors less and equal to/more than 4 cm showed worse progression and
      disease-free survival rates for the latter, even though the type of surgery
      (nephron-sparing or radical) had no significant impact. Patients with
      extracapsular carcinoma >=4 cm, treated with nephron-sparing surgery, had a
      particularly poor prognosis. CONCLUSIONS. The conservative management can be
      cautiously suggested for renal cancers up to 7cm, since the prognosis worsens
      proportionally with the diameter increase, with no statistical difference for
      both nephron-sparing and radical surgery. Nephron-sparing surgery proved to be
      the suitable treatment modality also for pT3a tumors measuring <4 cm, whereas
      when the tumor size increases, an adequate intraoperative evaluation of
      peritumoral tissues is essential to rule out fat infiltration. These results
      comply with the few similar studies available in literature, and suggest the
      possibility of designing a prospective study aiming at comparing conservative and
      radical surgery in the management of renal carcinoma up to 7 cm.

PMID- 21086399
TI  - [Blind traumas of the scrotum: three case reports].
AB  - The blind traumas of the scrotum are an uncommon event; references, iconography
      and descriptions of the clinical development of scrotal syndromes are poor. The
      scrotum and the didimal or funicular structures are often involved in different
      conditions. The authors are reporting on three interesting cases (for patients'
      age, mechanism of traumatism and anatomic damage), gathered from a series of 12
      cases of blind traumas of the scrotum, observed during 2 years (2005-2006). They
      include the iconography related to each single case, and emphasize the uncertain
      role of ultrasonography with color Doppler for a correct diagnosis. The clinical
      evolution and the long-term damage to gonad functionality are presented.

PMID- 21086400
TI  - [Evolution and progress in bladder replacement].
AB  - Nowadays, the first choice after radical cystectomy both in male and in female
      patients is no more urinary diversion, but bladder replacement surgery through
      orthotopic reconstruction. In 2006 we carried out a mail interview among Italian
      Urology Departments about urinary diversions and orthotopic neobladders; the
      choice for orthotopic neobladder had increased compared to a previous interview
      administered five years before. As far as the type of orthotopic neobladders are
      concerned, it was evident that Italian urologists prefer to use the ileal
      reservoir, preferably the Studer's neobladder, followed by VIP; the use of Camey
      II is decreasing while Y-neobladder has gained many consents, being preferred to
      Hautmann's reservoir. The findings of this interview suggest that the ideal
      orthotopic neobladder hasn't been proposed, yet, and that Italian urologists are
      still looking for easier and more reliable solutions.

PMID- 21086401
TI  - [Alpha1 adrenoceptors in human urinary tract:expression, distribution and
      clinical implications].
AB  - Adrenergic receptors (ARs) are a class of proteins belonging to the G
      proteincoupled receptor family. Pharmacological and molecular studies allowed
      dividing ARs into three different categories: alpha1, alpha2 and beta. In this
      review, we focused on alpha1 ARs and alpha1 AR antagonists, since alpha1 ARs play
      an important role in the pathophysiology of a number of urinary tract (UT)
      dysfunctions. alpha1 ARs are widely expressed in human UT; in particular, the
      three ureter areas (distal, medial and proximal) show different patterns of
      receptor expression (i.e. distal > medial = proximal), giving the molecular basis
      for the use of alpha1 ARs antagonist in the expulsive therapy of distal ureter
      calculi. Bladder areas are characterized by important differences among trigone,
      detrusor and neck, the first showing a different pattern of expression compared
      to the other parts. Further, there are evidences of both density and subtype
      gender-dependent expressions. alpha1 ARs expression in prostate and detrusor is a
      widely investigated area of research, mainly due to the clinical impact of benign
      prostatic hyperplasia (BPH). Urethra has not been well studied in human, although
      it plays a role in the control of continence. Studies carried out on alpha1 AR
      subtype expression in the UT indicate that, although the presence of each subtype
      is observed, alpha1A firstly and then alpha1D ARs seem to be more expressed than
      alpha1B ARs. Thus, drugs that demonstrate high alpha1A/D AR selectivity have
      drawn the researchers' attention. As it relates specifically to the alpha1 AR
      antagonists used in the treatment of lower UT symptoms, the concept of
      uroselectivity has been operationally defined; indeed, in a number of recent
      publications uroselectivity has been defined as the degree to which a given
      compound inhibits norepinephrine-induced increase in urinary muscle contractions
      and/or its propensity to generate unwanted cardiovascular effects, such as
      decreases in blood pressure.

PMID- 21086402
TI  - [Human biobank in uro-oncological research].
AB  - PURPOSE. Uro-oncological translational research requires clinical data and human
      biological tissues collected within a biological tissue bank (BTB). We are hereby
      outlining ethic-legal, methodological and technical issues of a BTB establishment
      process, focusing particularly on prostate cancer and Italian setting. MATERIALS
      AND METHODS. Review of literature data, and national and international
      regulations and guidelines; direct field experience of urological BTB; counseling
      of the different professionals involved. RESULTS. Within a BTB establishment
      process, it is of utmost importance to protect the donors' privacy and rights
      through the programmatic adoption of the following procedures: 1) informed
      consent; 2) confidentiality protection thanks to anonymity of biological
      specimens and use of an "honest broker" method; 3) identification of a single
      responsible researcher; 4) dedicated and protected location; 5) approval of the
      Ethical Committee. There are two main organizational models of BTB: "systematic",
      i.e. collecting specimens from all patients and through the same methodology;
      "project-driven", i.e. prospectively selecting patients for a specific study and
      using the specific methods required by researchers. In the preliminary step it is
      necessary to establish detailed protocols of sampling and crioconservation
      techniques, and methods of validation and quality control. For prostate tissue
      sampling, several techniques have been described such as specimens of alternate
      slices, macro dissection, Tru-Cut. CONCLUSIONS. Today BTBs are necessary in order
      to support molecular and translational research in uro-oncology, and to overcome
      the limits of the research based only on clinicalpathological data. Ethic-legal
      and methodological issues related to BTBs are still requiring specific
      legislation and standardization of techniques.

PMID- 21086403
TI  - [Circumcision: what do we cut when we are cutting?].
AB  - The term circumcision refers to partial or complete excision of the foreskin.
      There are three types of circumcision: ritual circumcision, performed for
      religious practice, as a rite of passage, usually during neonatal or
      transpubertal age; prophylactic circumcision, as preventive measure against
      future potential diseases; therapeutic circumcision, performed because of an
      evident pathology of the foreskin with clear medical indications. The
      investigation on the meaning of the ritual circumcision goes beyond the
      boundaries of the present paper; we are referring to anthropological literature
      to better understand its origin and reasons. Prophylactic circumcision spread
      among English-speaking peoples in the nineteenth century as a means against
      masturbation. In the twentieth century prevention against cancer, urinary
      infections, sexually transmitted diseases and, eventually, AIDS took over. The
      controversy about prophylactic circumcision is increasing nowadays in the United
      States whereas in the other English-speaking countries the procedure has almost
      disappeared and this represents what Edward Wallerstein calls "the uniquely
      American medical enigma". There are many interpretations for prophylactic
      circumcision and its lasting success in the United States. Each explanation
      probably hits the target only partially because this procedure takes its roots in
      the cultural history of the above mentioned country and in the relation with its
      puritan origins. Therapeutic circumcision is performed because of a clear and
      evident pathology of the prepuce. The embryological development of the prepuce is
      completed at the sixteenth week of pregnancy. At birth, this tissue covers the
      glans without an apparent plane of cleavage and should be defined as 'non
      retractile prepuce' instead of 'phymosis'. The prepuce in its free development
      becomes completely retractile at puberty. These evolutionary concepts about
      prepuce have been described by Douglas Gairdner in 1948 and Jacob Oster in 1968.
      The prepuce is an integrant part of the male genital system. It has three
      functions: protective, immunological and sexual. The extremely complex
      innervation of the prepuce explains its sensibility and makes it an extraordinary
      erogenous zone. In view of these features, the excision of the prepuce
      necessarily interferes with the patient's sexual function, and possibly involves
      serious psychological concerns. Circumcision represents a minor surgical
      procedure but, like any other surgical techniques, can result in complications:
      A) operative: hemorrhage, removal of too much skin from the penile shaft
      infection; B) post-operative: sepsis, urethrocutaneous fistula, gangrene of the
      penis; C) long-term complications: meatal stenosis, skin bridge between the glans
      and the penile shaft. Sometimes complications are severe and can cause death of
      the patient, especially during ritual circumcision. Given these aspects, a well
      informed consent is mandatory both in terms of potential complications linked to
      surgical procedures, and in terms of sexual and psychological consequences.

PMID- 21086404
TI  - [Effect of an LH-RH analogue on adhesion molecules in human prostate cancer
      cells].
AB  - BACKGROUND. The reduction in or the loss of the cell-cell adhesion often
      characterizes epithelial tumor initiation and progression. In the present study,
      we investigated the effects of the LH-RH analogue Leuprorelin acetate (LA), alone
      or associated with Dihydrotestosterone (DHT), on the expression of the adhesion
      proteins E-cadherin, alpha-, beta- and gamma-catenin in androgen-sensitive
      (LNCaP) and -insensitive (PC-3 and DU-145) prostate cancer cells. MATERIALS AND
      METHODS. Protein expression was evaluated by Western blotting on cells treated
      for 48 h with LA (10-11 or 10-6 M) and 10-9 M DHT, alone or combined. RESULTS. In
      LNCaP cells, all the above mentioned molecules are expressed. PC-3 cells lack
      alpha-catenin, while DU-145 cells only express beta- and gamma-catenin. In both
      LNCaP and PC-3 cells two truncated forms (97 and 35 kDa) of E-cadherin are
      present other than the functional protein (120 kDa). In LNCaP cells, no
      significant changes in E-cadherin (120 and 97 kDa) level were produced by DHT,
      while the 35 kDa fragment was reduced by 34%. LA increased the full length E
      cadherin (26-30%) as well as the two fragments (30-49%). The addition of DHT to
      LA significantly reduced the analogue-induced E-cadherin raising. In LNCaP cells
      beta- and gamma-catenin were up-regulated either by DHT (24% and 20%,
      respectively) or LA (up to 18% and up to 40%, respectively), while the expression
      of alpha-catenin was not modified. The combined DHT/LA treatment results in a
      less marked increase in beta- and gamma-catenin levels. In PC-3 cells no changes
      in adhesion molecule expression were produced by LA treatment, while in DU-145
      cells the analogue determined an appreciable reduction in beta- (20%) and gamma
      catenin (up to 35%) levels. CONCLUSIONS: The up-regulation of E-cadherin, beta-
      and gamma-catenin in LNCaP cells by LA may be considered as another feature of
      the direct antitumor LH-RH analogue activity, as it may contribute to the
      maintenance/restoration of the normal architecture of prostate epithelium. The LA
      induced modifications of catenins in DU-145 cells are worth some further
      investigations.

PMID- 21086405
TI  - [Efficacy and safety of endoscopic treatment of ureteral stones in pediatric
      age].
AB  - Ureteroscopy procedures in pediatric age are becoming more and more common thanks
      to the availability of smaller caliber instruments, and of improved endoscopic
      techniques. The efficacy of this procedure in pediatric age is still discussed
      nowadays. This paper aims at reviewing all cases of ureteral lithiasis treated by
      ureteroscopy plus intracorporeal lithotripsy (ULT), as well as verifying efficacy
      and safety of this procedure in pediatric age. MATERIALS AND METHODS. From July
      2002 to May 2006, 37 patients (26 female, 11 male; mean age 7.4 years; range 2
      17) were treated by ULT for ureteral stones: 30 in distal, 4 in middle and 3 in
      proximal ureter. Median size of stones was 7mm (range 3-13mm). Dilation of the
      ureteral meatus was necessary in 2 patients only. Endoscopic procedure was
      similar to adult patients. Outcomes were statistically compared with current
      literature data. RESULTS. In 36 (97.3%) out of 37 patients ULT proved successful.
      All patients having stones in distal (30) and middle (4) ureter were stone-free
      at the end of treatment. Stone migration into the kidney pelvis occurred in 1
      patient with proximal ureter stones (66.7% stone-free rate): an ESWL treatment
      was therefore performed. 1 case only (2.7%) developed a perioperative
      complication (stone migration). Hematuria and flank pain in 4 patients (10.8%)
      were the most common reported post-operative complications. A stone-free state
      was confirmed at 1 and 3 months for all 36 patients. There was no evidence of
      ureteral strictures and/or ureteral refluxes. CONCLUSIONS. Smaller caliber
      ureteroscopes confirmed ULT as the first-choice treatment procedure in children
      affected by ureteral lithiasis, thanks to its efficacy and safety.

PMID- 21086406
TI  - [Sexual rehabilitation with intracavernous PGE1 injections and oral drug
      administration in diabetic patients non-responder to oral therapy alone].
AB  - Diabetes is an important risk factor in erectile dysfunction (ED), acting via
      several mechanisms. We assessed the efficacy of intracavernous injections (ICI)
      rehabilitation and oral systematic therapy in diabetic patients, as well as the
      response of controls to oral therapy 'on demand'. MATERIALS AND METHODS. Sixteen
      diabetic patients with ED were treated with vasoactive drugs orally when needed,
      without satisfactory erections. The patients underwent then ICI rehabilitation
      with PGE1 20 mcg twice weekly for 4 weeks, followed by the administration of oral
      drugs twice weekly for 4 weeks. Before and after rehabilitation, the patients
      completed a detailed anamnestic protocol to study their libido (always present);
      they answered questions Q3 and Q4 of the IIEF questionnaire. During ICI, a study
      with dynamic echocolordoppler (ECCD) was carried out. All patients had Type 2
      diabetes: 10 were treated with oral antidiabetics, 4 were treated with insulin,
      and in the other 2 patients, treated with insulin, a sensitive neuropathy of the
      lower limbs was diagnosed. Fourteen patients were treated with antihypertensive
      drugs. RESULTS. Before rehabilitation, the mean responses to questions 3 and 4 of
      the IIEF (International Index of Erectile Function) questionnaire were 1.6 and
      1.5 respectively; after rehabilitation, the mean responses were 2.68 and 2.5,
      respectively. The ECCD test showed an arterial component in 4 cases and a high
      end-diastolic velocity (EDV) in 14 cases. Four patients (25%), 2 of which had
      neuropathy, and 2 were in advanced age, did not respond to PGE1 or to oral
      therapy, 4 patients (25%) (2 treated with insulin and 2 by oral therapy)
      responded to ICI but not to oral therapy, while 8 patients (50%) showed a good
      response to both injectable and oral therapy, with good Q3 and Q4 scores.
      CONCLUSIONS. Good endothelial function appears to be essential for the
      maintenance of acceptable erectile function. Diabetes has a negative effect on
      this function, as does hypoxia and low perfusion. Based on the principle that a
      good erection improves endothelial function, we tried to determine if oral
      systematic and intracavernous rehabilitation would improve erectile function in
      diabetic patients. The results indicate that diabetes interferes with erectile
      function, compromising the effects of the vasoactive drugs. However, integrated
      systematic rehabilitation appears to allow a good erectile response to both
      intracavernous and oral therapy in a large number of cases. Therefore, we support
      this kind of rehabilitative protocol in the treatment of ED in diabetic patients.

PMID- 21086407
TI  - [Intravenous treatment of postoperative pain in urologic surgery: comparison
      between analgesics].
AB  - The need for efficaciously treating acute postoperative pain arises primarily
      from the observation that pain is associated with modifications of organs and
      systems that can become extremely detrimental to the patients; the antalgic
      treatment, besides its ethic aspect, plays therefore an essential role since it
      can enormously improve the patient's outcomes, significantly reducing mortality,
      morbidity and discomfort. In the postoperative antalgic therapy, it is possible
      to associate molecules of different pharmacological classes: the aim of our study
      is to compare different combinations between opioids, Ketorolac and Paracetamol
      in 75 operations of urologic surgery; to assess any side effects and the
      postoperative pain (through the VNS scale) and, if necessary, to administer
      supplementary doses of Tramadol in order to complete the pre-arranged pain
      therapy. The statistical analysis of data demonstrates first how different
      antalgic medicaments can enhance each other, highlighting the greater
      effectiveness of Ketorolac compared to Paracetamol during the awakening period,
      at the pre-established dosages. Moreover, the study presents the slight
      occurrence of side effects during the postoperative period, of no importance in
      most cases: we can therefore come to the conclusion that the association between
      different drugs could result in a reduction in the single given dosages, and
      would probably be co-responsible of the low incidence of iatrogenic sequelae.

PMID- 21086408
TI  - Three-dimensional conformal radiotherapy in localized carcinoma of prostate:
      preliminary reports of toxicity in dose-escalation treatment.
AB  - PURPOSE. Many studies confirmed the evidence of a dose-response relationship in
      prostate cancer. Escalation of dose using conventional techniques is however
      limited by rectal tolerance. IMRT and 3D-CRT have been designed to allow dose
      escalation while not exceeding rectal tolerance. We evaluated the acute and early
      late tolerance to surrounding organs upon dose escalation from 70 to 78 Gy in 3D
      CRT setting, in order to introduce the IMRT process as a routine practice in
      prostate cancer treatment. MATERIALS AND METHODS. We compared clinical data from
      35 patients with localized adenocarcinoma of the prostate, who received 70 Gy
      within a traditional reconstructed three-dimensional treatment planning, and data
      from 72 patients who received 78 Gy within a threedimensional conformal setting.
      In order to respect rectal tolerance in the higher dose group, limits were set
      for rectum doses, and simulation procedures were standardized. We evaluated
      radiation morbidity (acute and late gastrointestinal and genitourinary toxicity)
      using the Radiation Therapy Oncology Group scoring criteria (RTOG scale).
      RESULTS. Increasing doses from 70 Gy to 78 Gy resulted in no significant
      difference for acute and late effects. CONCLUSION. A procedural standardization
      aiming at minimizing day-by-day variation, as well as a more consistent dose
      distribution to critical organs may significantly reduce the risk of increased
      toxicity in dose-escalation setting.

PMID- 21086409
TI  - [Sensitivity and specificity evaluation of endorectal magnetic resonance imaging
      and transrectal sonography in the staging of prostate cancer].
AB  - OBJECTIVES. Nowadays endorectal probes for Magnetic Resonance Imaging (MRI) have
      better resolutions, which allows to acquire high-level images of prostate and to
      improve the MRI sensitivity and specificity to determine the cancer volume and
      the extraprostatic extension. The objective of the present study is to evaluate
      the sensitivity and diagnostic accuracy of endorectal MRI for identifying the
      local extension of prostate carcinoma compared to transrectal sonography (TRUS)
      of prostate. MATERIALS AND METHODS. The study included 81 patients with clinical
      suspect of cancer and/or elevated values of serum prostate specific antigen
      (PSA), who underwent endorectal MRI with 1.5 T endorectal probe before
      transrectal biopsy. Patients with localized prostate cancer underwent radical
      surgery. The results of endorectal MRI were compared to those of TRUS and
      histopathological examination outcomes. RESULTS. 15 of the 81 enrolled patients
      had extraprostatic localization of cancer, which was assessed through TRUS in 4
      cases only (26%), and through MRI in 7 cases (46%). A seminal vesicle involvement
      was present in 10 patients, detected by MRI in 5 cases and in no cases by TRUS.
      DISCUSSION AND CONCLUSIONS. Data are similar to the findings collected by several
      Authors. The endorectal MRI has a better accuracy in staging prostate cancer
      compared to TRUS. Nevertheless, this procedure has some limits: little
      availability of equipment in hospitals, physicians' little experience, and higher
      costs compared to TRUS.

PMID- 21086410
TI  - [A case of particular diffusion of prostate cancer].
AB  - Neoplastic diffusion can occur due to dissemination, continuity, through
      lymphatic or haematic vessels, or, more rarely originate from surgical
      instruments. We report a particular case of prostate cancer spread. A 64-year-old
      man was diagnosed with undifferentiated prostate cancer through prostate biopsy.
      The patient was treated with a total androgenic block allowing a decrease in PSA
      blood level. The patient, wishing to regain his sexual activity compromised by
      hormonal therapy, interrupted the treatment spontaneously and unchecked. 19
      months later he contacted us again: we had to hospitalize him due to a 12-hour
      anuresis. A urgent right transcutaneous nephrostomy was carried out, yielding an
      improvement in the patient's condition. A descending pyelography carried out by
      means of nephrostomy revealed a completely reduced urethral lumen. During the
      following surgery for transcutaneous urinary derivation we observed the two
      ureters entangled in whitish tissue, spreading bilaterally up to the renal
      pelvis. The histological examination of tissue samples showed the presence of
      neoplastic metastasis of prostatic origin. We assume that this neoplastic
      diffusion has occurred due to permeability through the lymphatic vessels of the
      urethral wall, producing a subsequent neoplasm growth: this has been limited by
      the urethral connective sheath, thus preventing its wide diffusion to the
      surrounding tissues, but fostering its spreading upwards along the ureter
      pathway.

PMID- 21086411
TI  - [Transperineal TRUS-guided prostate biopsy].
AB  - Prostate biopsy can be performed through different approaches, with several
      differences in patient preparation, procedural technique and post-biopsy patient
      management. On the basis of our personal experience, and comparing it with
      literature data, this paper presents our data reviews regarding enema and
      antibiotic prophylaxis administration, biopsy technique, prostate sampling, core
      pathological management and post-operative management. We also provide a possible
      standardization of these procedures in patients undergoing transperineal TRUS
      guided prostate biopsy. We accordingly classify antibiotic prophylaxis and bowel
      preparation as optional/advisable, ultrasound prostate examination before biopsy
      and local anaesthesia as recommended. Prostate sampling should be performed with
      at least 8 cores, to be increased proportionally to prostate volume. Each sample
      should be sent to the pathologist in single containers, according to the pre
      embedding sandwich method. Finally, the patient should be evaluated for early
      complications before discharging, and for delayed complications within one month
      after the procedure.

PMID- 21086412
TI  - [Testicular cancer. Open questions: prevention, early diagnosis and infertility].
AB  - Testicular cancer is the most common malignancy in men aged 15-35 years.
      Histologically, testicular germ-cell tumors have two main subtypes: pure seminoma
      and nonseminoma. Knowing the histopathological tumor type and detecting the
      relevant prognostic factors helps to guide the subsequent therapeutic course. At
      present there are no recommendations for testicular cancer screening in healthy
      young men, even among men showing high risk; however, a testicular cancer should
      be diagnosed as soon as a young man presents with suggestive signs and symptoms.
      Furthermore, thanks to highly effective treatments including surgery,
      chemotherapy, and radiation therapy, it is very important to effectively manage
      secondary prevention and improve these patients' quality of life. Secondary
      prevention of relapses or secondary malignancy onsets should be carried out
      through a regular follow-up of the patient; in selected cases of positive family
      history, it is possible to perform genome-wide analyses aiming at searching the
      genes possibly causing testicular germ-cell tumor in affected first-degree male
      relatives. Long-term therapies can yield infertility and sexual dysfunction,
      issues gaining more and more importance from a clinical point of view. Sperm
      cryopreservation should be systematically offered to all requiring patients;
      moreover, screening for gonadal dysfunction should be considered in the follow-up
      of testicular cancer survivors, with the aim of hormone supplementation in
      symptomatic patients.

PMID- 21086413
TI  - [Transitional cell carcinoma of the prostate].
AB  - Transitional cell carcinoma of the prostate (TCCP) has become a well recognized
      entity, showing an increasing incidence due to the growing research awareness.
      TCCP is part of the well known pan-urothelial disease: the urologist, therefore,
      is strongly recommended to consider the prostate at any time in the management of
      superficial and invasive bladder cancer. Several cases are diagnosed in
      association with bladder cancer (secondary TCCP): primary prostatic transitional
      cell carcinoma arises 'de novo' as first tumour of the prostate urothelium and is
      rare. Prognosis depends on the prostate invasion degree. No reliable staging
      systems are presently available. Non-invasive TCCP can be successfully treated
      with conservative means (TUR +/- BCG), whereas stromal invasive TCCP must be
      aggressively treated with radical cystectomy. TCCP can interphere with surgeon's
      decisions about urinary diversion in patients undergoing radical cystectomy for
      urothelial cancer.

PMID- 21086414
TI  - [Radical prostatectomy: which quality of life?].
AB  - The aim of the present study was to evaluate quality of life in patients
      submitted to radical prostatectomy, by correlating the results of the
      postoperative condition with follow- up data at 6 and 12 months. MATERIALS AND
      METHODS. Between october 2004 and december 2005, 68 patients - mean age 68 (range
      49-76) - treated with radical retro-pubic prostatectomy for localized prostate
      cancer (T2a, T2b, No, Mo) were consecutively enrolled onto the study. All
      patients underwent sexual as well as urinary incontinence rehabilitation, showing
      good compliance. We evaluated quality of life before prostatectomy (T0), 6 (T1)
      and 12 (T2) months after surgery through the Short Form 36 questionnaire, for
      which an analysis of variance for repeated measures was carried out. Patients
      were interviewed by our department psychologist regarding urinary incontinence
      and erectile dysfunction. All patients were disease-free at the time of
      evaluation. RESULTS. No significant differences were observed between physical
      and mental health indices. Conversely, a significant improvement (p<0.001) was
      seen in all SF-36-questionnaire 8 scales, comparing preoperative T0 values with
      T1 and T2 values. Of the 68 patients, 53 (78%) no longer needed pads at the T2
      follow-up, while 15 (22%) reported using 3-4 pads/day. A significant worsening of
      the sexual function (maintenance of erection) was observed in 51 (75%) patients,
      who had reported having normal sexual activity preoperatively (T0). On the other
      hand, 17 (25%) patients reported having an adequate erection to engage in sexual
      intercourse. CONCLUSIONS. Despite the differences observed in physical and mental
      health scores during the three periods evaluated (T0, T1 and T2), overall quality
      of life does not appear to have been greatly compromised by surgery. At T2 follow
      up, in fact, all 68 patients reported to be satisfied with having undergone
      radical prostatectomy because of its benefits in terms of survival and its
      limited effects on their quality of life.

PMID- 21086416
TI  - Sclerosing Sertoli cell tumor of the testis.
AB  - Sclerosing Sertoli cell tumor of the testis is a very rare neoplasm. To date only
      19 cases have been reported in the literature. We present the twentieth case in a
      39 yearold man treated with conservative surgery with a review of the
      pathological and urological literature.

PMID- 21086415
TI  - [An alternative dosing regimen with tadalafil 3 times/week in the treatment of
      erectile dysfunction:italian data from the SURE study].
AB  - To evaluate the preference for 2 dosing regimens of tadalafil 20 mg, on demand or
      3 times/week, in Italian men affected by erectile dysfunction (ED). MATERIALS AND
      METHODS. SURE is a multicenter, crossover, open-label study, involving 94 urology
      centers in Italy. Patients aged 18 or more, affected by ED for at least 3 months
      were enrolled into the study and randomized to a tadalafil 20 mg treatment on
      demand or 3 times/week for 5-6 weeks. After a 1-week washout period, patients
      were crossed over to the alternate regimen for 5-6 weeks. A treatment preference
      question (TPQ) was used to determine the preferred treatment regimen. IIEF and
      SEP questionnaires were used as efficacy measures. RESULTS. 1058 men, mean age
      54.8 years, were randomized to treatment. Overall, 59.1% of patients preferred
      the on-demand regimen and 41.9% preferred the 3 times/week dosing regimen. Both
      regimens were efficacious and well tolerated. CONCLUSIONS. Tadalafil is effective
      and well tolerated whether used both on demand and three times/week. Patients
      should be given the possibility to choose the best treatment regimen according to
      personal needs and preferences.

PMID- 21086417
TI  - [The clinical and pathological comments from a case of sarcomatoid renal
      carcinoma].
AB  - Sarcomatoid renal carcinoma represents 1-5% of primitive tumours of the kidney.
      MATERIALS AND METHODS. A young man aged 34 presented with left side colic pain,
      preceded two days earlier by hematuria without pain; no previous complaints.
      Echotomography was performed revealing a tumour lesion of the upper left renal
      pole, which was subsequently confirmed by computerized tomography scanning, with
      a maximum diameter of approximately 6cm, and evidence of multiple lymph nodes
      with increased volume. A left-side nephroadrenalectomy was performed with
      locoregional lymphadenectomy; a sarcomatoid renal carcinoma with massive
      metastases in 4/19 excised lymph nodes was shown through histological
      examination. IL-2 therapy was commenced but interrupted due to intolerance. After
      only three months the disease resumed locally with diffuse lymph nodes metastases
      and multiple encephalic metastases. A carboplatinum and vinorelbine therapy was
      started; the possibility of an allogeneic transplant with non-myeloablative
      conditioning ("miniallogeneic") was suggested, though being impossible to be
      performed due to the further rapid disease progression. The patient died after
      approximately 10 months. CONCLUSIONS. Sarcomatoid renal carcinoma is
      characterised histologically by closely interconnected epithelial and connective
      tissue elements; sarcomatous cells seem to originate from a phenotype conversion
      to carcinomatous cells, as they both belong to the same DNA clone. Their
      behaviour is very aggressive and the prognosis is unfavourable: 6-month average
      survival after diagnosis. Radical nephrectomy is still the main therapeutic
      approach, although it is has no significant influence on prognosis and survival
      rate. This case showed an approximately 10-month patient's survival, with some
      different chemotherapeutic approaches being followed (first IL-2 and then
      carboplatinum) after surgery.

PMID- 21086418
TI  - [Professor Michelangelo Rizzo].

PMID- 21086419
TI  - 1H and 13C assignments of two new macrocyclic lactones isolated from Streptomyces
      sp. 211726 and revised assignments of azalomycins F3a, F4a and F5a.
AB  - Azalomycin F(4a) 2-ethylpentyl ester (1) and Azalomycin F(5a) 2-ethylpentyl ester
      (2), two new macrocyclic lactones, along with three known compounds of
      Azalomycins F(3a) (3), F(4a) (4) and F(5a) (5), were identified from metabolites
      of Streptomyces sp. 211726 isolated from mangrove rhizosphere soil. The complete
      (1)H and (13)C assignments of these compounds were achieved by using (1)H, (13)C,
      DEPT, HSQC, (1)H-(1)H COSY and HMBC spectra, and the relative stereochemistry of
      5 was first elucidated on the basis of proton-proton coupling constants, NOESY
      and IR spectra. Moreover, some errors in the (1)H and (13)C assignments published
      of 3, 4 and 5 were found and revised. 1 and 2 were active against Candida
      albicans, and exhibited moderate cytotoxicity against HCT-116 cell line.

PMID- 21086425
TI  - Separation science and macromolecular characterization.

PMID- 21086426
TI  - Analysis of polyolefin stabilizers and their degradation products.
AB  - Polymeric materials are complex samples, as they contain various groups of
      additives, compounding ingredients, and fillers. An important group of additives
      are stabilizers. Efficient stabilization is essential especially for
      polypropylene, as it is sensitive to oxidation and radical attack due to the
      numerous tertiary carbon atoms in its structure. How long a polymer will be
      sufficiently stabilized can be deduced from the contained amount of intact
      stabilizer. Different approaches for the analysis of stabilizers in polyolefins
      are available, which include sample preparation with subsequent chromatographic
      separation as well as direct analysis techniques. In round-robin tests,
      stabilizer concentrations obtained varied strongly. This shows the demand for
      reliable and robust methods. Stabilizers get consumed while protecting the
      polymer and are then present as degradation products. They were observed while
      quantifying intact stabilizers, in migration studies, and - if volatile - in
      emission studies of polymers. Furthermore, e.g. interactions with other polymer
      ingredients or irradiation degraded stabilizers. The identification of
      degradation products provides a better insight into the reactions associated with
      stabilization. Their quantitation makes it possible to deduce the original level
      of stabilization. Furthermore, polymer ingredients degrading stabilizers can be
      identified. Knowledge on these interactions contributes significantly to improved
      polymer stabilization.

PMID- 21086427
TI  - Selective improvement of tumor necrosis factor capture in a cytokine
      hemoadsorption device using immobilized anti-tumor necrosis factor.
AB  - Sepsis is a harmful hyper-inflammatory state characterized by overproduction of
      cytokines. Removal of these cytokines using an extracorporeal device is a
      potential therapy for sepsis. We are developing a cytokine adsorption device
      (CAD) filled with porous polymer beads which efficiently depletes middle
      molecular weight cytokines from a circulating solution. However, removal of one
      of our targeted cytokines, tumor necrosis factor (TNF), has been significantly
      lower than other smaller cytokines. We addressed this issue by incorporating anti
      TNF antibodies on the outer surface of the beads. We demonstrated that covalent
      immobilization of anti-TNF increases overall TNF capture from 55% (using
      unmodified beads) to 69%. Passive adsorption increases TNF capture to over 99%.
      Beads containing adsorbed anti-TNF showed no significant loss in their ability to
      remove smaller cytokines, as tested using interleukin-6 (IL-6) and interleukin-10
      (IL-10). We also detail a novel method for quantifying surface-bound ligand on a
      solid substrate. This assay enabled us to rapidly test several methods of
      antibody immobilization and their appropriate controls using dramatically fewer
      resources. These new adsorbed anti-TNF beads provide an additional level of
      control over a device which previously was restricted to nonspecific cytokine
      adsorption. This combined approach will continue to be optimized as more
      information becomes available about which cytokines play the most important role
      in sepsis.

PMID- 21086428
TI  - Effect of trisodium citrate on electrolytic deposition of hydroxyapatite
      coatings.
AB  - Hydroxyapatite coatings were deposited on the titanium substrate by using various
      content Na3Cit as an organic modifier in electrolytes. The influence of the
      Na3Cit on the sizes of the HA crystals during electrolytic deposition was
      investigated under different molar ratio of Na3Cit to calcium ions. The
      experimental results showed that the size of HA crystal was well controlled by
      the addition of Na3Cit. When the molar ratio of Na3Cit to calcium ions was equal
      or greater than five, the obtained HA coating consisted of nanosized crystals.
      The HA nanoparticles were precipitated without a precursor phase when the molar
      ratio of Na3Cit to calcium ions was five; otherwise, the CaP coating experienced
      a phase conversion from octacalcium phosphate (OCP) to HA during the ELD. The
      effect of pH on saturation indexes with respect to hydroxyapatite, OCP, and
      dicalcium dihydrogen phosphate of these electrolytes was calculated by a computer
      program PHREEQC. The calculation showed the nucleation of OCP as the precursor
      during the deposition could be inhibited with increasing Na3Cit content in the
      electrolytes.

PMID- 21086429
TI  - Evaluation of porcine hydrated dermis augmented repair in a fascial defect model.
AB  - Surgical mesh composed of extracellular matrix promotes healing of difficult soft
      tissue and orthopedic repairs in preclinical and clinical trials. In this study,
      a novel extracellular matrix prepared from porcine hydrated dermis was evaluated
      in an in vivo fascial defect model in sheep. Fascial defects were created, and
      then acutely repaired with surgical mesh. Healed surgical sites were evaluated
      grossly, histologically, and biomechanically at 6 and 12 weeks. Porcine hydrated
      dermis extracellular matrix performed favorably compared to negative control
      empty defects and native fascia, with minimal gross adhesion, low histologic
      inflammatory scores, and significantly greater tensile strength of the healing
      surgical site when compared with native fascia.

PMID- 21086430
TI  - Controllable dual-release of dexamethasone and bovine serum albumin from
      PLGA/beta-tricalcium phosphate composite scaffolds.
AB  - Localized dual-drug delivery from biodegradable scaffolds is an important
      strategy in tissue engineering. In this study, porous poly(L-lactide-co
      glycolide) (PLGA)/beta-tricalcium phosphate scaffolds containing both
      dexamethasone (Dex) and bovine serum albumin (BSA) were prepared by incorporating
      Dex-loaded and BSA-loaded microspheres into the scaffolds. PLGA microspheres
      containing Dex or BSA were prepared by spray-drying and double emulsion/solvent
      evaporation, respectively. In vitro release studies indicated that microspheres
      prepared from PLGA in 3:1 molar ratio of L-lactide/glycolide and 89.5 kDa
      relative molecular mass showed prolonged release profiles compared with those
      prepared from PLGA in 1:1 L-lactide/glycolide molar ratio and 30.5 kDa relative
      molecular mass. Additionally, introduction of poly(ethylene glycol) in the PLGA
      chain could improve the encapsulation efficiency and reduce the release rate.
      Based on the above results, controllable dual-release of Dex and BSA with
      relatively higher or lower release rate was achieved by incorporating Dex-loaded
      and BSA-loaded microspheres with different release profiles into the PLGA/beta
      tricalcium phosphate scaffolds.

PMID- 21086437
TI  - Molecular weight determination of high molecular mass (glyco)proteins using CGE
      on-a-chip, planar SDS-PAGE and MALDI-TOF-MS.
AB  - The molecular weights (MW) of seven (glyco)proteins, of which five were plasma
      derived, with MWs higher than 200 kDa were determined with three techniques: CGE
      on-a-chip, SDS-PAGE and MALDI-TOF-MS. While the analysis of medium to high MW
      proteins with SDS-PAGE was an already well-established technique, the usefulness
      of MALDI-TOF-MS for the exact MW determination of high mass proteins was only
      partly described in literature so far. CGE-on-a-chip is the newest of all three
      applied techniques and was so far not applicable. Therefore, it was not evaluated
      for high MW (glyco)proteins. All proteins were analyzed under nonreducing as well
      as reducing conditions. In this work, it was demonstrated that all three
      described techniques were capable of determining the MW of all high molecular
      weight (glyco)proteins. The noncommercial CGE-on-a-chip assay allowed for the
      first time the electrophoretic separation of proteins in the MW range from 14 to
      1000 kDa. MW assignment was limited to 500 kDa in the case of SDS-PAGE and 660
      kDa in the case of the high MW CGE-on-a-chip assay. With the proper matrix and
      sample preparation, analysis with a standard MALDI-TOF-MS provided accurate MWs
      for all high MW proteins up to 1 MDa.

PMID- 21086438
TI  - Sensitized phosphorescence as detection method for the enantioseparation of
      bupropion by capillary electrophoresis.
AB  - A new CE detection method was developed for the chiral drug bupropion (a second
      generation antidepressant), based on phosphorescence both in the direct and in
      the sensitized mode using pulsed laser excitation at 266 nm. Electrokinetic
      chromatography using 5 mM sulfated-alpha-CD as chiral selector in 25 mM phosphate
      buffer at pH 3 allowed the separation of bupropion enantiomers with a high chiral
      resolution (Rs>3). In the sensitized phosphorescence detection mode, excitation
      energy is transferred from the analyte to an acceptor (1-bromo-4
      napthhalenesulfonic acid or biacetyl) followed by time-resolved phosphorescence
      detection under deoxygenated buffer conditions. Using 2 * 10(-4) M biacetyl as
      the acceptor an LOD of 2 * 10(-7) M was obtained for each enantiomer, about 40
      times better than in the direct mode. Under these separation conditions, no
      significantly different phosphorescence lifetimes (measured on-line) were
      obtained for the two bupropion enantiomers. The suitability of the method was
      demonstrated with the quantification of bupropion in a pharmaceutical formulation
      and its determination in a spiked urine sample.

PMID- 21086439
TI  - Effects of an antagonist of neurokinin receptors 1, 2 and 3 on reproductive
      hormones in male beagle dogs.
AB  - BACKGROUND: SCH 206272, a neurokinin 1, 2, and 3 receptor antagonist,
      administered to beagle dogs results in testicular toxicity. Therefore, a series
      of experiments were conducted to determine whether this observed toxicity was
      associated with changes in reproductive hormones and hypothalamic gonadotrophin
      releasing hormone (GnRH) levels. METHODS: Male beagle dogs were administered 30
      mg/kg SCH 206272 for up to 7 days. Blood samples were collected at the end of the
      dosing period for reproductive hormone analysis. Male reproductive organs were
      stained with hematoxylin and eosin and the hypothalamus was stained for GnRH.
      RESULTS: Intact male dogs exhibited SCH 206272-related decreases in pulsatility
      and magnitude of luteinizing hormone (LH) and testosterone, which were associated
      with seminiferous tubule degeneration, oligospermia, and epithelial atrophy in
      the prostate gland. Neutered dogs also exhibited SCH 206272-related decreases in
      LH and FSH. In a subsequent reversibility study, intact male dogs exhibited
      decreased LH, testosterone, and FSH, which exhibited recovery by 2 weeks post
      dosing; however, seminiferous tubule degeneration and oligospermia did not
      exhibit recovery by 2 weeks post-dosing. Dogs administered SCH 206272 also
      exhibited an increase in mean number of GnRH-containing neurons in the
      hypothalamus and an increase in GnRH mRNA/neuron, which exhibited recovery by 2
      weeks post-dosing. CONCLUSIONS: SCH 206272-dosed dogs exhibited rapid decreases
      in reproductive hormones and subsequent testicular pathology. Collectively, these
      changes in hormone levels suggest that the observed SCH 206272-related
      reproductive tract findings are the result of alterations in hypothalamic
      pituitary-gonadal function. However, a direct effect on the testes cannot be
      definitively ruled out.

PMID- 21086444
TI  - Exploring the factors determining the dynamics of different protein folds.
AB  - Normal mode analyses of homologous proteins at the family and superfamily level
      show that slow dynamics are similar and are preserved through evolution. This
      study investigates how the slow dynamics of proteins is affected by variation in
      the protein architecture and fold. For this purpose, we have used computer
      generated protein models based on idealized protein structures with varying
      folds. These are shown to be protein-like in their behavior, and they are used to
      investigate the influence of architecture and fold on the slow dynamics. We
      compared the dynamics of models having different folds but similar architecture
      and found the architecture to be the dominant factor for the slow dynamics.

PMID- 21086450
TI  - Single-molecule imaging of protein adsorption mechanisms to surfaces.
AB  - Protein-surface interactions cause the desirable effect of controlled protein
      adsorption onto biodevices as well as the undesirable effect of protein fouling.
      The key to controlling protein-surface adsorptions is to identify and quantify
      the main adsorption mechanisms: adsorptions that occur (1) while depositing a
      protein solution onto dry surfaces and (2) after the deposition onto wet
      surfaces. Bulk measurements cannot reveal the dynamic protein adsorption pathways
      and thus cannot differentiate between the two adsorption mechanisms. We imaged
      the interactions of single streptavidin molecules with hydrophobic fused-silica
      surfaces in real-time. We observed both adsorbed proteins on surfaces and
      diffusing proteins near surfaces and analyzed their adsorption kinetics. Our
      analysis shows that the protein solution deposition process is the primary
      mechanism of streptavidin adsorption onto surfaces at the subnanomolar to
      nanomolar protein concentrations. Furthermore, we found that hydrophilic fused
      silica surfaces can prevent the adsorption of streptavidin molecules.

PMID- 21086453
TI  - Non-label homogeneous protein detection based on laser interferometric photo
      thermal displacement measurement using aptamers.
AB  - Photo-thermal displacement measurement by laser interferometry involves the
      measurement of temperature change caused by illumination of the sample. To
      develop a system of detecting unlabeled homogeneous proteins based on laser
      interferometric measurement of photo-thermal displacement, we studied the
      interaction between aptamers and their target molecules by using thrombin and the
      thrombin aptamer as a model target and ligand, respectively. Because of the
      energy consumed by aptamer-thrombin interactions, the signals obtained from
      solutions containing aptamer-thrombin mixtures varied depending on the thrombin
      concentration. We propose that this method involving the use of aptamers and
      photo-thermal displacement measurement will provide a biomolecular detection
      system for rapid diagnosis.

PMID- 21086455
TI  - Bioethanol production from dedicated energy crops and residues in Arkansas, USA.
AB  - Globally, one of the major technologic goals is to achieve cost-effective
      lignocellulosic ethanol production from biomass feedstocks. Lignocellulosic
      biomass of four dedicated energy crops [giant reed (Arundo donax L.),
      elephantgrass (Pennisetum purpureum (Schumach), Miscanthus * giganteus (Illinois
      clone), and (clone Q42641) {hybrid of Miscanthus sinensis Anderss. and Miscanthus
      sacchariflorus (Maxim)}, Hack. called giant miscanthus, and sugarcane clone US 84
      1028 (Saccharum L. spp. hybrid)] and residues from two crops [soybean (Glycine
      max (L.) Merr.) litter and rice (Oryza sativa L.) husk] were tested for
      bioethanol production using cellulose solvent-based lignocellulose fractionation
      (CSLF) pretreatment and enzymatic (cellulase) hydrolysis. Giant miscanthus
      (Illinois), giant reed, giant miscanthus (Q42641), elephantgrass, and sugarcane
      all yielded higher amount of glucose on a biomass dry weight basis (0.290-0.331
      g/g), than did rice husk (0.181 g/g) and soybean litter (0.186 g/g). To reduce
      the capital investment for energy consumption in fermentation, we used a self
      flocculating yeast strain (SPSC01) to ferment the lignocellulosic biomass
      hydrolysates. Bioethanol production was ~0.1 g/g in dedicated energy crops and
      less in two crop residues. These methods and data can help to develop a cost
      effective downstream process for bioethanol production.

PMID- 21086461
TI  - Accumulation and distribution of cadmium and lead in wheat (Triticum aestivum L.)
      grown in contaminated soils from the oasis, north-west China.
AB  - BACKGROUND: Crops grown in soils contaminated by heavy metals are an important
      avenue for toxic metals entering the human food chain. The objectives of our
      study were to investigate the accumulation and distribution of cadmium (Cd) and
      lead (Pb) in wheat plants cultivated in arid soils spiked with different doses of
      heavy metal, as well as bioavailability of these metals in the contaminated arid
      soils from the oasis, north-west China. RESULTS: The concentrations of Cd in the
      roots of wheat plants were about 5, 14 and 8 times higher than those in the
      shoots, shells and grains, respectively. The concentrations of Pb in the roots
      were about 23, 76 and 683 times higher than those in the shoots, shells and
      grains, respectively. Grains contained 11-14% and 0.1-0.2% of Cd and Pb found in
      roots of wheat plants. The bioconcentration factor (BCF) is the ratio of metal
      concentration in plant tissues and metal concentration in their rooted soils. The
      average BCF of Cd and Pb in grains was 0.6270 and 0.0007. Cd and Pb contents in
      different parts of wheat plants mainly correlated with the bound-to-carbonate
      metal fractions in contaminated arid soils. CONCLUSION: The preliminary study
      indicated that Cd and Pb were predominantly accumulated and distributed in wheat
      roots and shoots, and only a small proportion of these metals can reach the
      grains. The carbonate fractions mainly contributed to Cd and Pb bioavailability
      in contaminated arid soils.

PMID- 21086471
TI  - 2011: an important year in the science of food and agriculture.

PMID- 21086474
TI  - Knockdown of TSP50 inhibits cell proliferation and induces apoptosis in P19
      cells.
AB  - Earlier studies identified testes-specific protease 50 (TSP50), which encodes a
      threonine protease, and showed that it was abnormally reactivated in many breast
      cancer biopsies. Further, it was shown to be negatively regulated by the p53
      gene. However, little is known about the biological function of TSP50. In this
      study, we applied RNA interference to knockdown TSP50 gene expression in P19
      murine embryonal carcinoma stem cells and tested whether this modulated the cell
      phenotype. The results showed that downregulation of TSP50 expression not only
      reduced cell proliferation, colony formation, and migration but also induced cell
      apoptosis. Further investigation revealed that knockdown of TSP50 resulted in
      greater sensitivity to doxorubicin-induced apoptosis and that activation of
      caspase-3 was involved in this process.

PMID- 21086475
TI  - The reduced form of coenzyme Q10 mediates distinct effects on cholesterol
      metabolism at the transcriptional and metabolite level in SAMP1 mice.
AB  - Studies in humans and mice indicate a role for coenzyme Q(10) (CoQ(10)) in gene
      expression. To analyze this function in relation to metabolism, SAMP1 mice were
      supplemented with the reduced (ubiquinol) or oxidized (ubiquinone) form of
      CoQ(10) (500 mg/kg BW/d) for 14 months. Microarray analyses in liver tissues of
      SAMP1 mice identified 946 genes as differentially expressed between ubiquinol
      treated and control animals (>=1.5-fold, P < 0.05). Text mining analyses revealed
      for a part of the ubiquinol-regulated genes, a functional connection in PPARalpha
      and LXR/RXR signalling pathways. Because these pathways are involved in
      cholesterol homeostasis, relevant metabolites were determined by gas
      chromatography/mass spectrometry (GC/MS). We found a significant increase of
      desmosterol (2.0-fold, P < 0.001) in the liver of ubiquinol-supplemented SAMP1
      mice when related to control animals. In agreement, cholesterol concentrations
      were also distinctly increased (1.3-fold, P = 0.057). The Q(10)H(2)-induced
      PPARalpha and LXR/RXR gene expression signatures and effects on cholesterol
      metabolism were not apparent for the oxidized form of CoQ(10). In conclusion, the
      reduced form of CoQ(10) mediates distinct effects on cholesterol metabolism at
      the transcriptional and metabolite level in SAMP1 mice.

PMID- 21086477
TI  - Nickel-catalyzed [3+2+2] cycloadditions between alkynylidenecyclopropanes and
      activated alkenes.

PMID- 21086478
TI  - A flexible nonporous heterogeneous catalyst for size-selective oxidation through
      a bottom-up approach.

PMID- 21086479
TI  - Zeotype organic-inorganic ionic crystals: facile cation exchange and controllable
      sorption properties.

PMID- 21086482
TI  - myo-Inositol trispyrophosphate: a novel allosteric effector of hemoglobin with
      high permeation selectivity across the red blood cell plasma membrane.
AB  - myo-Inositol trispyrophosphate (ITPP), a novel membrane-permeant allosteric
      effector of hemoglobin (Hb), enhances the regulated oxygen release capacity of
      red blood cells, thus counteracting the effects of hypoxia in diseases such as
      cancer and cardiovascular ailments. ITPP-induced shifting of the oxygen
      hemoglobin equilibrium curve in red blood cells (RBCs) was inhibited by DIDS and
      NAP-taurine, indicating that band 3 protein, an anion transporter mainly
      localized on the RBC membrane, allows ITPP entry into RBCs. The maximum
      intracellular concentration of ITPP, determined by ion chromatography, was
      5.5*10(-3) M, whereas a drop in concentration to the limit of detection was
      observed in NAP-taurine-treated RBCs. The dissociation constant of ITPP binding
      to RBC ghosts was found to be 1.72*10(-5) M. All data obtained indicate that ITPP
      uptake is mediated by band 3 protein and is thus highly tissue-selective towards
      RBCs, a feature of major importance for its potential therapeutic use.

PMID- 21086483
TI  - An aptamer-based nanobiosensor for real-time measurements of ATP dynamics.

PMID- 21086484
TI  - Influence of N-alkyl substituents and counterions on the structural and
      mesomorphic properties of guanidinium salts: experiment and quantum chemical
      calculations.
AB  - A series of N-4-(4'-alkoxybiphenyl)-N',N',N",N"-tetramethylguanidinium salts was
      synthesized with varying alkoxy chain lengths and additional N-alkyl
      substituents, each with a number of different counterions. X-ray crystal
      structure analyses of 1b I, 1b PF(6), 2a I, and 4a I reveal bilayer structures in
      the solid state and, for the 1b and 1b PF(6) salts, a hydrogen-bond-type
      connectivity between the guanidinium N-H group and the anion is found. For the N
      alkyl homologues 2a I and 4a I the anion is still oriented close to the head
      group, although at a larger distance. Ion pairs are present also in solution, as
      demonstrated by (1)H NMR: the N-H chemical shift shows a good linear correlation
      with the radius, and hence the hardness, of the anion. The intramolecular
      conformational flexibility of 1b I, 2b I, 3b I, and 4b I was studied by
      temperature-dependent (1)H NMR spectroscopy and discrete activation barriers were
      determined for rotations about each of the three C-N partial double bonds of the
      guanidinium core. The relative heights of the individual barriers change between
      the N-H and the N-alkylguanidinium salts. A fourth barrier is observed for the
      rotation about the N-biphenyl bond. DFT calculations of charge densities show
      that the positive charge resides primarily on the central carbon atom. Rotational
      barriers were calculated for N'-substituted 2-amino-1,3-dimethylimidazolidinium
      cations as models, and are in qualitatively good agreement with the NMR data.
      Mesomorphic properties were studied by differential-scanning calorimetry,
      polarizing optical microscopy, and X-ray diffraction (WAXS/SAXS). All liquid
      crystalline guanidinium salts exhibit smectic A mesophases. Clearing temperatures
      show a linear correlation with the anionic radius. Substitution of the N-H group
      with methyl, ethyl, or propyl results in decreasing mesophase widths and a
      concomitant shrinkage of the layer spacings.

PMID- 21086485
TI  - Temperature response of PNIPAM derivatives at planar surfaces: comparison between
      polyelectrolyte multilayers and adsorbed microgels.
AB  - Two strategies for the design of thermosensitive coatings based on poly-N
      isopropyl acrylamide (PNIPAM) derivatives are presented: 1) polyelectrolyte
      multilayers containing a diblock copolymer with a large PNIPAM block and 2)
      adsorption of PNIPAM microgels. The multilayers show only a small but
      irreversible response to the increase of outer temperature due to the strong
      interdigitation between the charged part and the temperature-sensitive block,
      while the adsorbed microgels show a pronounced and reversible response. It will
      be shown that the microgel number density can be easily controlled at the
      substrate. The swelling and shrinking of two extremes in density are
      characterized: densely packed microgels, which are considered as a film, and
      individual microgels, which are able to swell and shrink also lateral to the
      surface.

PMID- 21086490
TI  - Irreversible effects of retinoic acid pulse on Xenopus jaw morphogenesis: new
      insight into cranial neural crest specification.
AB  - Jaws are formed by cephalic neural crest (CNCCs) and mesodermal cells migrating
      to the first pharyngeal arch (PA1). A complex signaling network involving
      different PA1 components then establishes the jaw morphogenetic program. To
      gather insight on this developmental process, in this study, we analyze the
      teratogenic effects of brief (1-15 min) pulses of low doses of retinoic acid (RA:
      0.25-2 uM) or RA agonists administered to early Xenopus laevis (X.l.) embryos. We
      show that these brief pulses of RA cause permanent craniofacial defects
      specifically when treatments are performed during a 6-hr window (developmental
      stages NF15-NF23) that covers the period of CNCCs maintenance, migration, and
      specification. Earlier or later treatments have no effect. Similar treatments
      performed at slightly different developmental stages within this temporal window
      give rise to different spectra of malformations. The RA-dependent teratogenic
      effects observed in Xenopus can be partially rescued by folinic acid. We provide
      evidence suggesting that in Xenopus, as in the mouse, RA causes craniofacial
      malformations by perturbing signaling to CNCCs. Differently from the mouse, where
      RA affects CNCCs only at the end of their migration, in Xenopus, RA has an effect
      on CNCCs during all the period ranging from their exit from the neural tube until
      their arrival in the PA1. Our findings provide a conceptual framework to
      understand the origin of individual facial features and the evolution of
      different craniofacial morphotypes.

PMID- 21086491
TI  - A different approach to validating screening assays for developmental toxicity.
AB  - BACKGROUND: There continue to be many efforts around the world to develop assays
      that are shorter than the traditional embryofetal developmental toxicity assay,
      or use fewer or no mammals, or use less compound, or have all three attributes.
      Each assay developer needs to test the putative assay against a set of
      performance standards, which traditionally has involved testing the assays
      against a list of compounds that are generally recognized as "positive" or
      "negative" in vivo. However, developmental toxicity is highly conditional, being
      particularly dependent on magnitude (i.e. dose) and timing of exposure, which
      makes it difficult to develop lists of compounds neatly assigned as developmental
      toxicants or not. APPROACH: Here we offer an alternative approach for the
      evaluation of developmental toxicity assays based on exposures. Exposures are
      classified as "positive" or "negative" in a system, depending on the compound and
      the internal concentration. Although this linkage to "internal dose" departs from
      the recent approaches to validation, it fits well with widely accepted principles
      of developmental toxicology. CONCLUSIONS: This paper introduces this concept,
      discusses some of the benefits and drawbacks of such an approach, and lays out
      the steps we propose to implement it for the evaluation of developmental toxicity
      assays.

PMID- 21086492
TI  - Pushing the limits forward: transradial superficial femoral artery stenting.
AB  - Percutaneous revascularization of superficial femoral artery (SFA) is
      increasingly carried out to treat patients with peripheral vascular disease and
      either intermittent claudication or critical limb ischemia. Transradial vascular
      access is increasingly adopted for invasive procedures due to reduced access-site
      complications and improved patient's comfort, compared with transfemoral.
      However, compared with coronary interventions, the adoption of transradial access
      in peripheral procedures is limited. Concerning SFA interventions, transradial
      access is usually prevented by the distance between the vascular access and the
      target lesion, which extends over the length of the currently available devices.
      Thanks to technical improvements, resulting in specifically dedicated low-profile
      equipment with adequate shaft length availability, transradial access is now
      feasible for the treatment of selected SFA lesions. We report the first two cases
      of SFA stenting performed by transradial access with a new specifically developed
      self-expanding nitinol stent with extended delivery system length. This report
      suggests that, with proper technique and specifically dedicated equipment,
      transradial SFA stenting is feasible. Treatment of SFA disease by transradial
      route, allowing for immediate post-procedure walking and simultaneous bilateral
      interventions, may represent an alternative for effective treatment of selected
      patients with SFA lesions.

PMID- 21086493
TI  - Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a
      patient with mental retardation.
AB  - CHD6 is an ATP-dependent chromatin-remodeling enzyme, which has been implicated
      as a crucial component for maintaining and regulating chromatin structure. CHD6
      belongs to the largest subfamily, subfamily III (CHD6-9), of the chromodomain
      helicase DNA (CHD-binding protein) family of enzymes (CHD1-9). Here we report on
      a female patient with a balanced translocation t(4;20)(q33;q12) presenting with
      severe mental retardation and brachydactyly of the toes. We identified the
      translocation breakpoint in intron 27 of CHD6 at 20q12, while the 4q33 breakpoint
      was intergenic. Northern blot analysis demonstrated the CHD6 mRNA in the
      patient's lymphoblastoid cells was decreased to ~50% of the control cells. To
      investigate the cellular mechanism of diseases resulting from decreased CHD
      subfamily III proteins, we knocked down CHD6 or CHD7 by RNA interference in HeLa
      cells and analyzed chromosome alignment. The both CHD6- and CHD7-knockdown cells
      showed increased frequency of misaligned chromosomes on metaphase plates.
      Moreover, an elevated frequency of aneuploidy, the major cause of miscarriages
      and mental retardation, was observed in patients with CHD6 and CHD7
      haploinsufficiency. These results suggest that CHD6 and CHD7 play important roles
      in chromatin assembly during mitosis and that mitotic delay and/or impaired cell
      proliferation may be associated with pathogenesis of the diseases caused by CHD6
      or CHD7 mutations.

PMID- 21086494
TI  - The Kounis syndrome in everolimus-eluting stents and paclitaxel-eluting stents.

PMID- 21086498
TI  - Genetic repression of mouse VEGF expression regulates coagulation cascade.
AB  - VEGF is an important growth factor in embryonic development and functional
      maintenance of adult organs. Single allele inactivation of VEGF leads to
      embryonic lethality and many conditional disruptions show dramatic phenotypes or
      reduced viabilities. To overcome this burden, a reversible system, which was used
      in the regulation of VEGF expression and functional studies of many tissues and
      organs in adult, was developed. VEGF is known for expression in many tissues and
      high expression in platelets. Repression of VEGF expression showed significant
      defect in bleeding time and clotting time. In mouse model of LPS-induced blood
      hypercoagulation, significant reduction of plasma thrombin-antithrombin formation
      was observed in VEGF repressed mice, and tissues expressed different modes of
      damages. These results indicate that VEGF regulates coagulation cascade and may
      affect sepsis. This is the first genetic evidence of direct link between VEGF
      transcription and coagulation cascade. Studies using this system may help us to
      find out how VEGF regulates coagulation cascade and provide new strategies in
      treating coagulation related diseases.

PMID- 21086516
TI  - Improving the sensitivity of MASCOT search results validation by combining new
      features with Bayesian nonparametric model.
AB  - The probability-based search engine MASCOT has been widely used to identify
      peptides and proteins in shotgun proteomic research. Most subsequent quality
      control methods filter out ambiguous assignments according to the ion score and
      thresholds provided by MASCOT. On the basis of target-decoy database search
      strategy, we evaluated the performance of several filter methods on MASCOT search
      results and demonstrated that using filter boundaries on two-dimensional feature
      spaces, the MASCOT ion score and its relative score can improve the sensitivity
      of the filter process. Furthermore, using a linear combination of several
      characteristics of the assigned peptides, including the MASCOT scores, 15
      previously employed features, and some newly introduced features, we applied a
      Bayesian nonparametric model to MASCOT search results and validated more
      correctly identified peptides in control and complex data sets than those could
      be validated by empirical score thresholds.

PMID- 21086517
TI  - Deciphering the role of the thermodynamic and kinetic stabilities of SH3 domains
      on their aggregation inside bacteria.
AB  - The formation of insoluble deposits by globular proteins underlies the onset of
      many human diseases. Recent studies suggest a relationship between the
      thermodynamic stability of proteins and their in vivo aggregation. However, it
      has been argued that, in the cell, the occurrence of irreversible aggregation
      might shift the system from equilibrium, in such a way that it could be the rate
      of unfolding and associated kinetic stability instead of the conformational
      stability that controls protein deposition. This is an important but difficult to
      decipher question, because kinetic and thermodynamic stabilities appear usually
      correlated. Here we address this issue by comparing the in vitro folding kinetics
      and stability features of a set of non-natural SH3 domains with their aggregation
      properties when expressed in bacteria. In addition, we compare the in vitro
      stability of the isolated domains with their effective stability in conditions
      that mimic the cytosolic environment. Overall, the data argue in favor of a
      thermodynamic rather than a kinetic control of the intracellular aggregation
      propensities of small globular proteins in which folding and unfolding velocities
      largely exceed aggregation rates. These results have implications regarding the
      evolution of proteins.

PMID- 21086519
TI  - Monitoring of an ATP-binding aptamer and its conformational changes using an
      alpha-hemolysin nanopore.
AB  - An aptamer is a specific oligonucleotide sequence that spontaneously forms a
      secondary structure capable of selectively binding an analyte. An aptamer's
      conformation is the key to specific binding of a target molecule, even in the
      case of very closely related targets. Nanopores are a sensitive tool for the
      single-molecule analysis of DNA, peptides, and proteins transporting through the
      pore. Herein, a single alpha-hemolysin natural nanopore is utilized to sense the
      conformational changes of an adenosine 5'-triphosphate (ATP)-binding aptamer
      (ABA). The known DNA sequence of the ABA is used as a model to develop real-time
      monitoring of molecular conformational changes that occur by binding targets. The
      native, folded ABA structure has a nanopore unfolding time of 4.17 ms, compared
      with 0.29 ms for the ABA:ATP complex. A complementary 14-mer strand, which binds
      the ABA sequence in the key nucleic acids responsible for folding, forms linear
      duplex DNA, resulting in a nanopore transit time of 0.50 ms and a higher capture
      probability than that of the folded ABA oligomer. Competition assays between the
      ABA:ATP and ABA:reporter complexes are carried out, and the results suggest that
      the ABA:ATP complex is formed preferentially. The nanopore allows for the
      detection of an ABA in its folded, ATP-bound, and linear conformations.

PMID- 21086523
TI  - The Yearbook provides broad but thorough coverage of developments within the
      discipline. Preface.

PMID- 21086520
TI  - Mechanobiology: correlation between mechanical stability of microcapsules studied
      by AFM and impact of cell-induced stresses.

PMID- 21086524
TI  - The new biological anthropology: bringing Washburn's new physical anthropology
      into 2010 and beyond--the 2008 AAPA luncheon lecture.
AB  - Nearly 60 years ago, Sherwood Washburn issued a call for a "New Physical
      Anthropology," a transition from measurement and classification toward a focus on
      the processes and mechanisms of evolutionary change. He advocated
      multidisciplinary and interdisciplinary approaches to the understanding of human
      behavior, biology, and history. Many interpret this as a call for a practice that
      is both biological and anthropological. Is this what we do? Are we biological
      anthropologists yet? In this essay, I explore what we, Physical Anthropologists,
      as a discipline are doing in the context of a New Physical Anthropology, where we
      might be headed, and why this discussion is crucial to our relevance.

PMID- 21086525
TI  - Nonadaptive processes in primate and human evolution.
AB  - Evolutionary biology has tended to focus on adaptive evolution by positive
      selection as the primum mobile of evolutionary trajectories in species while
      underestimating the importance of nonadaptive evolutionary processes. In this
      review, I describe evidence that suggests that primate and human evolution has
      been strongly influenced by nonadaptive processes, particularly random genetic
      drift and mutation. This is evidenced by three fundamental effects: a relative
      relaxation of selective constraints (i.e., purifying selection), a relative
      increase in the fixation of slightly deleterious mutations, and a general
      reduction in the efficacy of positive selection. These effects are observed in
      protein-coding, regulatory regions, and in gene expression data, as well as in an
      augmentation of fixation of large-scale mutations, including duplicated genes,
      mobile genetic elements, and nuclear mitochondrial DNA. The evidence suggests a
      general population-level explanation such as a reduction in effective population
      size (N(e)). This would have tipped the balance between the evolutionary forces
      of natural selection and random genetic drift toward genetic drift for variants
      having small selective effects. After describing these proximate effects, I
      describe the potential consequences of these effects for primate and human
      evolution. For example, an increase in the fixation of slightly deleterious
      mutations could potentially have led to an increase in the fixation rate of
      compensatory mutations that act to suppress the effects of slightly deleterious
      substitutions. The potential consequences of compensatory evolution for the
      evolution of novel gene functions and in potentially confounding the detection of
      positively selected genes are explored. The consequences of the passive
      accumulation of large-scale genomic mutations by genetic drift are unclear,
      though evidence suggests that new gene copies as well as insertions of
      transposable elements into genes can potentially lead to adaptive phenotypes.
      Finally, because a decrease in selective constraint at the genetic level is
      expected to have effects at the morphological level, I review studies that
      compare rates of morphological change in various mammalian and island populations
      where N(e) is reduced. Furthermore, I discuss evidence that suggests that
      craniofacial morphology in the Homo lineage has shifted from an evolutionary rate
      constrained by purifying selection toward a neutral evolutionary rate.

PMID- 21086526
TI  - The big and small of it: how body size evolves.
AB  - Body size is a biological variable of fundamental importance and plays a central
      role in analyses of life history, sexual dimorphism, allometry, and natural and
      sexual selection. Yet, there remains a sizeable gulf in our understanding that
      lies between what we hypothesize influences change in size, from the point of
      view of ultimate causation, and what we know about how shifts in body size are
      regulated from a proximate perspective. I seek here to tie these two perspectives
      together, and specifically to argue that an understanding of the hormonal
      regulation of body size is necessary for constructing hypotheses regarding how
      body size evolves. Recent work using model organisms points to the
      insulin/insulin-like growth factor pathway as playing a key role in the
      regulation of growth, size, reproduction, and senescence. I review the role of
      various components of this pathway in regulating growth and size and illustrate
      the evidence for different ways in which these might work to generate differences
      in size in various organisms. Of particular interest are the tradeoffs between
      size and other life history traits produced by experimental alterations in this
      pathway. Recent work emphasizing the ways in which body size can be altered based
      on extrinsic factors provides the opportunity to link advances in uncovering the
      proximate bases of growth and size and offers an opportunity to frame new
      hypotheses regarding how variation in size evolves.

PMID- 21086527
TI  - Smell with inspiration: the evolutionary significance of olfaction.
AB  - The olfactory receptor gene family is the largest in the mammalian genome (and
      larger than any other gene family in any other species), comprising 1% of genes.
      Beginning with a genetic radiation in reptiles roughly 200 million years ago,
      terrestrial vertebrates can detect millions of odorants. Each species has an
      olfactory repertoire unique to the genetic makeup of that species. The human
      olfactory repertoire is quite diverse. Contrary to erroneously reported
      estimates, humans can detect millions of airborne odorants (volatiles) in quite
      small concentrations. We exhibit tremendous variation in our genes that control
      the receptors in our olfactory epithelium, and this may relate to variation in
      cross-cultural perception of and preference for odors. With age, humans
      experience differential olfactory dysfunction, with some odors remaining strong
      and others becoming increasingly faint. Olfactory dysfunction has been
      pathologically linked to depression and quality of life issues, neurodegenerative
      disorders, adult and childhood obesity, and decreased nutrition in elderly
      females. Human pheromones, a controversial subject, seem to be a natural
      phenomenon, with a small number identified in clinical studies. The consumer
      product industry (perfumes, food and beverage, and pesticides) devotes billions
      of dollars each year supporting olfactory research in an effort to enhance
      product design and marketing. With so many intersecting areas of research,
      anthropology has a tremendous contribution to make to this growing body of work
      that crosses traditional disciplinary lines and has a clear applied component.
      Also, anthropology could benefit from considering the power of the olfactory
      system in memory, behavioral and social cues, evolutionary history, mate choice,
      food decisions, and overall health.

PMID- 21086528
TI  - The late Middle Pleistocene hominin fossil record of eastern Asia: synthesis and
      review.
AB  - Traditionally, Middle Pleistocene hominin fossils that cannot be allocated to
      Homo erectus sensu lato or modern H. sapiens have been assigned to different
      specific taxa. For example, in eastern Asia, these hominin fossils have been
      classified as archaic, early, or premodern H. sapiens. An increasing number of
      Middle Pleistocene hominin fossils are currently being assigned to H.
      heidelbergensis. This is particularly the case for the African and European
      Middle Pleistocene hominin fossil record. There have been suggestions that
      perhaps the eastern Asian late Middle Pleistocene hominins can also be allocated
      to the H. heidelbergensis hypodigm. In this article, I review the current state
      of the late Middle Pleistocene hominin fossil record from eastern Asia and
      examine the various arguments for assigning these hominins to the different
      specific taxa. The two primary conclusions drawn from this review are as follows:
      1) little evidence currently exists in the eastern Asian Middle Pleistocene
      hominin fossil record to support their assignment to H. heidelbergensis; and 2)
      rather than add to the growing list of hominin fossil taxa by using taxonomic
      names like H. daliensis for northeast Asian fossils and H. mabaensis for
      Southeast Asian fossils, it is better to err on the side of caution and continue
      to use the term archaic H. sapiens to represent all of these hominin fossils.
      What should be evident from this review is the need for an increase in the
      quality and quantity of the eastern Asian hominin fossil data set. Fortunately,
      with the increasing number of large-scale multidisciplinary paleoanthropological
      field and laboratory research projects in eastern Asia, the record is quickly
      becoming better understood.

PMID- 21086529
TI  - Fossil evidence for the origin of Homo sapiens.
AB  - Our species Homo sapiens has never received a satisfactory morphological
      definition. Deriving partly from Linnaeus's exhortation simply to "know thyself,"
      and partly from the insistence by advocates of the Evolutionary Synthesis in the
      mid-20th Century that species are constantly transforming ephemera that by
      definition cannot be pinned down by morphology, this unfortunate situation has
      led to huge uncertainty over which hominid fossils ought to be included in H.
      sapiens, and even over which of them should be qualified as "archaic" or as
      "anatomically modern," a debate that is an oddity in the broader context of
      paleontology. Here, we propose a suite of features that seems to characterize all
      H. sapiens alive today, and we review the fossil evidence in light of those
      features, paying particular attention to the bipartite brow and the "chin" as
      examples of how, given the continuum from developmentally regulated genes to
      adult morphology, we might consider features preserved in fossil specimens in a
      comparative analysis that includes extant taxa. We also suggest that this
      perspective on the origination of novelty, which has gained a substantial
      foothold in the general field of evolutionary developmental biology, has an
      intellectual place in paleoanthropology and hominid systematics, including in
      defining our species, H. sapiens. Beginning solely with the distinctive living
      species reveals a startling variety in morphologies among late middle and late
      Pleistocene hominids, none of which can be plausibly attributed to H. sapiens/H.
      neanderthalensis admixture. Allowing for a slightly greater envelope of variation
      than exists today, basic "modern" morphology seems to have appeared significantly
      earlier in time than the first stirrings of the modern symbolic cognitive system.

PMID- 21086530
TI  - Beautiful is not (necessarily) right: overcoming the Phryne's trial syndrome.

PMID- 21086533
TI  - Binding of amyloid peptides to domain-swapped dimers of other amyloid-forming
      proteins may prevent their neurotoxicity.

PMID- 21086534
TI  - Effectiveness of melatonin treatment on circadian rhythm disturbances in
      dementia. Are there implications for delirium? A systematic review.
AB  - OBJECTIVE: Circadian rhythm disturbances, like sundowning, are seen in dementia.
      Because the circadian rhythm is regulated by the biological clock, melatonin
      might be effective in the treatment of these disturbances. We systematically
      studied the effect of melatonin treatment in patients with dementia. In addition,
      we elaborate on the possible effects one might expect of melatonin treatment in
      patients with delirium, since dementia and delirium are strongly related.
      Moreover, some evidence exists that sundowning in patients with dementia and the
      alterations in the sleep/wake cycle, seen in patients with delirium both
      originate from circadian rhythm disturbances. DESIGN: A systematic search of the
      literature, published between 1985 and April 2009, was performed using PubMed and
      other databases. All papers on melatonin treatment in dementia were retrieved.
      Effects of melatonin on circadian rhythm disturbances were scored by means of
      scoring sundowning/agitated behaviour, sleep quality and daytime functioning.
      RESULTS: Nine papers, including four randomised controlled trials (RCTs) (n =
      243), and five case series (n = 87) were reviewed. Two of the RCTs found a
      significant improvement on sundowning/agitated behaviour. All five case series
      found an improvement. The results on sleep quality and daytime functioning were
      inconclusive. CONCLUSION: Sundowning/agitated behaviour improves with melatonin
      treatment in patients with dementia. There are several arguments that sundowning
      in patients with dementia and the alterations in the sleep/wake cycle in patients
      with delirium have a common background, namely a disturbance of the circadian
      rhythm. This suggests that melatonin treatment could also have the same positive
      effects in patients with delirium.

PMID- 21086535
TI  - Late-life depression and the death of Queen Victoria.
AB  - OBJECTIVE: The objective of this study was to evaluate relationships between the
      death of Queen Victoria and the depressive episode she experienced during the
      last year of her life. METHODS: The last volume of Queen Victoria's personal
      Journal was reviewed from a geriatrician's perspective, tracing the onset and
      course of depressive symptoms from entries beginning on 17 August 1900 and ending
      on 13 January 1901, 9 days before her death. The Queen's own words are
      supplemented with observations from contemporaneous secondary sources. RESULTS:
      The antecedents of Queen Victoria's late-life depression, including multiple
      losses, disabilities, and chronic pain, taken together with the presentation of
      vegetative, affective, and late cognitive symptoms, suggested the presence of a
      distinctively geriatric major depressive disorder. The absence of any other
      medical condition to explain the clinical picture seemed probable but not
      certain. CONCLUSIONS: Although historians and biographers have long been aware of
      Queen Victoria's final depression, the emphasis has mostly been on her earlier
      and prolonged mourning for her husband Prince Albert. Re-examined now, the
      Queen's Journal suggests that a severe late-life depressive episode occurring
      approximately in her last 5 months contributed meaningfully to her death.

PMID- 21086536
TI  - Differences in perceptions regarding driving between young and old drivers and
      non-drivers in Japan.
AB  - OBJECTIVE: The issue of driving cessation for dementia patients is one of the
      urgent public health priorities in Japan and is often complicated, with family or
      social barriers yet to be sufficiently addressed. Because the possibility of
      dementia or family caregiving can befall anyone, we focused on the disparity in
      people's perceptions of driving as possible barriers. The present study aimed to
      assess perceptions of driving among the general public and examine differences in
      perceptions based on age and driving status. METHODS: A survey was conducted in a
      sample of the general public aged 40 and over in Japan. Respondents were 1010
      people who received a self-administered questionnaire that included questions
      regarding perceptions about driving and sociodemographic factors. RESULTS: The
      drivers that participated in this study tended to highly agree that 'driving is a
      "right" which we all deserve', compared with the non-drivers. The most common
      reason for reluctance to stop driving among drivers was the possible loss of
      personal mobility. Apart from transportation, older drivers were more likely than
      younger drivers to value the qualitative aspects of driving, for example, driving
      was viewed as 'a motivating factor in my life'. CONCLUSIONS: These disparities in
      the general public's perceptions about driving may be possible family or social
      barriers to driving cessation in the case of drivers with dementia. Our findings
      also suggest that when addressing the need for driving retirement, not only
      mobility but also the qualitative aspects of driving be paid more attention.

PMID- 21086537
TI  - Association between alcohol consumption and cognitive impairment in Southern
      Chinese older adults.
AB  - BACKGROUND: There is limited data on the effects of alcohol consumption on
      cognitive impairment in Chinese populations. OBJECTIVES: To investigate the
      association between alcohol consumption and the risk of cognitive impairment in
      Southern Chinese older adults in Hong Kong. METHOD: This was a cross-sectional
      study of 314 Chinese older participants, aged 65 years or over. Participants'
      socio-demographic, co-morbid diseases, alcohol drinking habits, and Mini Mental
      State Examination (MMSE) for cognitive function were obtained by a face-to-face
      interview. Participants were categorized into normal cognitive and cognitively
      impaired groups by education-adjusted MMSE cut-off scores. RESULT: The mean (SD)
      age of the participants was 79.9 (6.5) years. The average weekly alcohol
      consumption in the cognitively impaired group was significantly higher than that
      of the normal cognition group [mean (SD): 861.89 (673.03) versus 241.21 (276.26)
      grams per week respectively; p < 0.001, t-test]. Drinkers with light to moderate
      alcohol consumption were associated with higher MMSE scores than non-drinkers and
      heavy drinkers. Logistic regression analyses showed that heavy drinkers (> 400 g
      alcohol for men and > 280 g for women) were associated with an increased risk of
      cognitive impairment (OR = 4.99, 95%CI = 1.8-13.82), while light drinkers and
      moderated drinkers (< 400 g for men and < 280 g for women) were associated with
      reduced risks (OR = 0.32, 95%CI = 0.12-0.86; OR = 0.17, 95%CI = 0.06-0.51,
      respectively). Exercise and age were independent protective and risk factors
      respectively. CONCLUSION: Heavy alcohol consumption is associated with an
      increased risk of cognitive impairment while light to moderate alcohol
      consumption is associated with reduced risk among Southern Chinese older adults
      in Hong Kong.

PMID- 21086538
TI  - Detecting prodromal Alzheimer's disease in mild cognitive impairment: utility of
      the CAMCOG and other neuropsychological predictors.
AB  - BACKGROUND: The Cambridge cognitive examination (CAMCOG) is a mini
      neuropsychological battery which is well established and widely used. The utility
      of the CAMCOG in detecting prodromal Alzheimer's disease (AD) in patients with
      mild cognitive impairment (MCI) has not been determined. The objectives of this
      study are: to establish which subtests of cognitive domains contained within the
      CAMCOG are predictive of conversion to AD, to compare these with an extended
      version of the delayed word recall (DWR) test and to establish optimal cut points
      for all measures used. METHODS: 182 patients with MCI were identified from
      consecutive referrals to a memory clinic. Logistic regression, cox regression and
      receiver operating characteristic curve (ROC) analyses were conducted. RESULTS:
      The DWR displayed the best sensitivity (77%) and specificity (76%). The composite
      memory score contained within the CAMCOG achieved similar sensitivity (78%) and
      specificity (74%). The recognition component of the extended DWR demonstrated
      good specificity (85%) but poor sensitivity (57%). The optimal predictive model
      combined category fluency with the DWR and achieved predictive accuracy of 83%.
      CONCLUSION: The DWR, which is a test specifically designed to have high
      predictive accuracy for AD, performed best. The composite measure of memory
      contained within the CAMCOG performed similarly well. The DWR has the advantage
      of being brief, easy to administer and suitable for use in non-specialist
      settings. The CAMCOG takes longer to administer but provides information
      regarding additional cognitive domains and is sensitive to change over time.
      Category fluency may be usefully combined with the DWR to improve predictive
      accuracy.

PMID- 21086539
TI  - Effect of mood symptoms on recovery one year after stroke.
AB  - BACKGROUND: Depression and anxiety are the most common mood symptoms and
      psychological consequences of stroke. This study aimed to examine the influence
      of acute depression and anxiety symptoms on functional recovery and health
      related quality of life (HRQoL) one year after stroke. METHODS: At one month and
      one year after stroke, the prevalence and severity of depression and anxiety
      symptoms were examined in consecutively admitted patients, using the Hospital
      Anxiety and Depression Scale (HADS). Functional recovery was assessed using the
      Nottingham Extended Activities of Daily Living (NEADL) and HRQoL using the Stroke
      Specific Quality of Life scale (SSQOL). RESULTS: In 107 patients, the prevalence
      of depression and anxiety symptoms was 35% at one month and 36% and 34%,
      respectively, at one year. Depression symptoms were significantly associated with
      functional ability (r = -0.19, p < 0.05) and HRQoL (r = -0.41, p < 0.001) at one
      year. Anxiety symptoms were significantly associated with HRQoL (r = -0.33, p <
      0.001) only. Multivariate analyses indicated that both depression (beta = -0.33,
      p < 0.001) and anxiety (beta = -0.26, p < 0.01) symptoms explained some variance
      in HRQoL at one month and did not predict functional recovery or HRQoL at one
      year, after controlling for other independent variables such as stroke severity
      and pre-morbid conditions. DISCUSSION: Mood symptoms following acute stroke were
      associated with a poorer HRQoL one year later but only depression symptoms
      influenced functional recovery. Other clinical factors such as pre-morbid
      conditions may need to be taken into consideration when determining the effect of
      mood symptoms on stroke recovery.

PMID- 21086540
TI  - Citalopram versus other antidepressants for late-life depression: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To determine the efficacy and tolerability of citalopram when compared
      to other antidepressants for late-life depression (LLD). METHODS: We searched
      electronic databases and trial registries to identify randomized controlled
      trials comparing citalopram to other antidepressants for LLD. Study quality was
      assessed using the Cochrane collaboration risk of bias tool. We summarized the
      efficacy of citalopram compared to other antidepressants by examining rates of
      depression remission, depression response and change in depression symptom
      scores. Medication tolerability was assessed through trial withdrawals due
      adverse events and withdrawals due to any cause. We used meta-analysis to
      determine the odds ratios (OR) of efficacy and tolerability outcomes for
      citalopram compared to other antidepressants. RESULTS: Seven studies comparing
      citalopram (N = 647) to other antidepressants (N = 641) for LLD were identified
      including four studies with tricyclic comparators and three studies with non
      tricyclic comparators. Most of the studies had methodological limitations that
      placed them at risk for potential bias. The majority of studies reported no
      significant differences between citalopram and comparator medications for
      depression efficacy or tolerability outcomes. Meta-analysis did not find any
      significant differences between citalopram and other antidepressants for
      depression remission [OR = 0.84; 95%CI: 0.56-1.28] or for trial withdrawals due
      to adverse effects [OR = 0.70; 95%CI: 0.48-1.02]. CONCLUSIONS: Currently there
      are few studies directly comparing citalopram to other antidepressants for LLD.
      The small number of studies and methodological issues in many studies limit any
      conclusions about the relative efficacy and tolerability of citalopram compared
      to other antidepressants. Well-designed studies comparing citalopram to other
      antidepressants for LLD are required.

PMID- 21086541
TI  - Peritraumatic distress predicts posttraumatic stress symptoms in older people.

PMID- 21086542
TI  - Does treating Alzheimer's disease early, delay institutionalisation?

PMID- 21086543
TI  - The effects of music therapy on reducing agitation in patients with Alzheimer's
      disease, a pre-post study.

PMID- 21086544
TI  - The effect of four coffee types on normotensive rats and normal/hypertensive
      human volunteers.
AB  - Coffee is a commonly consumed beverage. The purpose of this study was to
      determine the effect of the four coffee types on blood pressure (BP). The
      caffeine percentage was tested on one cup (250 mL) of each type of coffee
      (Arabian, Turkish, American and an instant coffee preparation) using two methods.
      65 adult male rats and 400 healthy human volunteers were used in this study.
      Normotensive rats were treated orally with a single dose of normal saline with
      varying types of coffee. Normotensive and mildly hypertensive human volunteers
      were administered a cup (250 mL) of any type of coffee separately. Tail cuff and
      a strain-gauge plethysmograph were used to measure the systolic blood pressure
      (SBP), diastolic blood pressure (DBP) and heart rate (HR) of the rats, and
      volunteers, respectively before and 0.5, 1.0, 1.5, and 2 h post administration.
      The mean arterial pressure (MAP) was calculated mathematically using SBP and DBP.
      The alkaloidal percentage of different types of coffee showed the presence
      variable contents and amount of active materials. The study showed that Arabian,
      Turkish, American and instant coffee all have the potential to cause a BP
      lowering effect. Variable antimicrobial activities were recorded for the
      different types of coffee when tested bacteria.

PMID- 21086545
TI  - Effects of Nelumbo nucifera rhizome extract on cell proliferation and neuroblast
      differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia
      animal model.
AB  - A large aquatic herb, Nelumbo nucifera Gaertn, has psychopharmacological effects
      similar to minor tranquillizers and antistress agents. This study examined the
      effects of Nelumbo nucifera rhizome extracts (NRE) on cell proliferation and
      neuroblast differentiation in the hippocampal dentate gyrus (DG) of a rat model
      of scopolamine-induced amnesia. Immunohistochemical markers included Ki67, an
      endogenous marker for active cell cycle, and doublecortin (DCX), a marker for
      immature neurons and migratory neuroblasts. Scopolamine was administered for 28
      days via an ALzet minipump (44 mg/mL delivered at 2.5 uL/h). NRE was administered
      by gavage, 1 g/kg per day for 28 days. The administration of scopolamine
      significantly reduced the number of Ki67- and DCX-immunoreactive cells in the DG,
      whereas scopolamine did not induce any significant changes in mature neurons in
      the DG. The administration of NRE significantly ameliorated the scopolamine
      induced reduction of Ki67- and DCX-immunoreactive cells in the DG. In addition,
      the administration of NRE significantly restored the scopolamine-induced
      reduction of brain-derived neurotrophic factor in DG homogenates. These results
      suggest that NRE can ameliorate the scopolamine-induced reductions of cell
      proliferation, neuroblast differentiation and BDNF levels.

PMID- 21086546
TI  - Effect of berberine and Berberis aetnensis C. Presl. alkaloid extract on
      glutamate-evoked tissue transglutaminase up-regulation in astroglial cell
      cultures.
AB  - Berberis aetnensis C. Presl. is a bushy-spiny shrub common on Mount Etna (Sicily,
      Italy), containing various alkaloids with several pharmacological properties.
      This study assessed the effect of berberine and of the alkaloid extract of B.
      aetnensis roots on the glutamate-evoked tissue transglutaminase (TG2) up
      regulation in rat astrocyte primary cultures, used as an in vitro model of
      excitotoxicity. The findings show that the alkaloid extract of B. aetnensis roots
      consists mainly of berberine. Furthermore, berberine and the alkaloid extract of
      B. aetnensis roots were able to restore the oxidative status modified by
      glutamate and the levels of TG2 to control values. It was found that berberine or
      the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive
      production of glutamate, protein misfolding and aggregation, mitochondrial
      fragmentation, and neurodegeneration. Thus, it is suggested that berberine and
      the alkaloid extract of B. aetnensis roots, may represent a natural therapeutic
      strategy in the neuropathological conditions associated with excitotoxicity.

PMID- 21086547
TI  - Compared ability of garlic (Allium sativum) extract or alpha-tocopherol +
      magnesium association to reduce metabolic disorders and oxidative stress in
      diabetic rats.
AB  - Since some complications of diabetes mellitus may be caused or exacerbated by an
      oxidative stress, the protective effects of (1) a garlic (Allium sativum) aqueous
      extract or (2) a combination of alpha-tocopherol and magnesium were investigated
      comparatively in alloxan-diabetic rats. Garlic extract (1 mL of extract
      corresponding to 300 mg fresh garlic/kg) or alpha-tocopherol (100 mg/kg) +
      MgCl(2) (200 mg/kg body weight) were i.p. injected to rats, once a day for 4
      weeks. Lipid peroxidation levels and the activities of superoxide-dismutase,
      catalase and glutathione peroxidase were then measured in liver and pancreas.
      Under our experimental conditions, garlic extract or alpha-tocopherol + Mg were
      found to (1) significantly reduce the plasma levels of glucose, total cholesterol
      and triglyceride and (2) lactate dehydrogenase, alkaline phosphatase and
      transaminase activities in blood of diabetic animals. In addition, treatment with
      garlic extract or alpha-tocopherol + magnesium appeared to exert an antioxidative
      activity demonstrated (1) by the increase of catalase, superoxide-dismutase and
      glutathione-peroxidase activities in liver and pancreas, and (2) a lowering of
      lipid peroxidation level in these organs. In conclusion, both garlic extract and
      alpha-tocopherol + magnesium association were found to alleviate diabetes
      associated metabolic disorders and oxidative stress in rats.

PMID- 21086548
TI  - Inhibition of adhesion of Neisseria meningitidis to human epithelial cells by
      berry juice polyphenolic fractions.
AB  - The adhesion of pathogens to host tissues is the requirement for the initiation
      of the majority of infectious diseases. It was shown recently that the binding of
      Neisseria meningitidis pili to immobilized human epithelial cells is inhibited by
      molecular size fractions (10-100 kDa) of berry juices. Additionally, the isolated
      meningococcal pili bound to polyphenolic fractions of berry juices. The present
      study investigated the antiadhesive effects of berry juice polyphenolics against
      living meningococcal bacteria in a human epithelial cell culture model. The
      ability of bilberry, cranberry, crowberry and lingonberry juice polyphenolic
      fractions to inhibit the attachment of N. meningitidis bacteria to HEC-1B human
      epithelial cells in a cell culture model was examined. The antibacterial effect
      of the fractions was tested using a microtiter broth microdilution assay. The
      most effective adhesion inhibition of 75% was achieved with cranberry juice
      polyphenolic fraction followed by crowberry (63%), bilberry (63%) and lingonberry
      (57%) juice polyphenolic fractions. Bacterial survival rates after incubation
      with the fractions varied between 75-100%. The present results suggest berry
      juice polyphenols as inhibitors of adherence of N. meningitidis. Thus the binding
      of meningococci to berry juice polyphenols might be protective for the host
      against the infection.

PMID- 21086549
TI  - Sensitivity of beamformer source analysis to deficiencies in forward modeling.
AB  - Beamforming approaches have recently been developed for the field of
      electroencephalography (EEG) and magnetoencephalography (MEG) source analysis and
      opened up new applications within various fields of neuroscience. While the
      number of beamformer applications thus increases fast-paced, fundamental
      methodological considerations, especially the dependence of beamformer
      performance on leadfield accuracy, is still quite unclear. In this article, we
      present a systematic study on the influence of improper volume conductor modeling
      on the source reconstruction performance of an EEG-data based synthetic aperture
      magnetometry (SAM) beamforming approach. A finite element model of a human head
      is derived from multimodal MR images and serves as a realistic volume conductor
      model. By means of a theoretical analysis followed by a series of computer
      simulations insight is gained into beamformer performance with respect to
      reconstruction errors in peak location, peak amplitude, and peak width resulting
      from geometry and anisotropy volume conductor misspecifications, sensor noise,
      and insufficient sensor coverage. We conclude that depending on source position,
      sensor coverage, and accuracy of the volume conductor model, localization errors
      up to several centimeters must be expected. As we could show that the beamformer
      tries to find the best fitting leadfield (least squares) with respect to its
      scanning space, this result can be generalized to other localization methods.
      More specific, amplitude, and width of the beamformer peaks significantly depend
      on the interaction between noise and accuracy of the volume conductor model. The
      beamformer can strongly profit from a high signal-to-noise ratio, but this
      requires a sufficiently realistic volume conductor model.

PMID- 21086550
TI  - Mapping reliability in multicenter MRI: voxel-based morphometry and cortical
      thickness.
AB  - Multicenter structural MRI studies can have greater statistical power than single
      center studies. However, across-center differences in contrast sensitivity,
      spatial uniformity, etc., may lead to tissue classification or image registration
      differences that could reduce or wholly offset the enhanced statistical power of
      multicenter data. Prior work has validated volumetric multicenter MRI, but robust
      methods for assessing reliability and power of multisite analyses with voxel
      based morphometry (VBM) and cortical thickness measurement (CORT) are not yet
      available. We developed quantitative methods to investigate the reproducibility
      of VBM and CORT to detect group differences and estimate heritability when MRI
      scans from different scanners running different acquisition protocols in a
      multicenter setup are included. The method produces brain maps displaying
      information such as lowest detectable effect size (or heritability) and effective
      number of subjects in the multicenter study. We applied the method to a five-site
      multicenter calibration study using scanners from four different manufacturers,
      running different acquisition protocols. The reliability maps showed an overall
      good comparability between the sites, providing a reasonable gain in sensitivity
      in most parts of the brain. In large parts of the cerebrum and cortex scan
      pooling improved heritability estimates, with "effective-N" values upto the
      theoretical maximum. For some areas, "optimal-pool" maps indicated that leaving
      out a site would give better results. The reliability maps also reveal which
      brain regions are in any case difficult to measure reliably (e.g., around the
      thalamus). These tools will facilitate the design and analysis of multisite VBM
      and CORT studies for detecting group differences and estimating heritability.

PMID- 21086553
TI  - Relationships between the transcriptome and physiological indicators of
      reproduction in female rainbow trout over an annual cycle.
AB  - Normal transcriptomic patterns along the brain-pituitary-gonad-liver (BPGL) axis
      should be better characterized if endocrine-disrupting compound-induced changes
      in gene expression are to be understood. Female rainbow trout were studied over a
      complete year-long reproductive cycle. Tissue samples from pituitary, ovary, and
      liver were collected for microarray analysis using the 16K Genomic Research on
      Atlantic Salmon Project (GRASP) microarray and for quantitative polymerase chain
      reaction measures of estrogen receptor (ER) isoform messenger RNA (mRNA) levels.
      Plasma was collected to determine levels of circulating estradiol-17beta (E2),
      follicle-stimulating hormone (FSH), and luteinizing hormone (LH). As an a priori
      hypothesis, changes in gene expression were correlated to either circulating
      levels of E2, FSH, and LH, or ER mRNAs quantified by quantitative polymerase
      chain reaction. In the liver, most transcriptomic patterns correlated to levels
      of either E2, LH, or ERs. Fewer ovarian transcripts could be correlated to levels
      of E2, ERalpha, or FSH. No significant associations were obvious in the
      pituitary. As a post hoc hypothesis, changes in transcript abundance were
      compared with microarray features with known roles in gonadal maturation. Many
      altered transcripts in the ovary correlated to transcript levels of estradiol 17
      beta-dehydrogenase 8 or 17 B HSD12, or to glycoprotein alpha chain 1 or 2. In the
      pituitary, genes involved with the growth axis (e.g., growth hormone, insulin
      related growth factor binding protein) correlated with the most transcripts.
      These results suggest that transcriptional networks along the BPGL axis may be
      regulated by factors other than circulating steroid hormones.

PMID- 21086554
TI  - Tissue residue concentrations of organohalogens and trace elements in adult
      Pacific salmon returning to the Fraser River, British Columbia, Canada.
AB  - We report measured concentrations of organohalogens and trace elements in muscle
      and eggs of returning wild Pacific sockeye and chinook salmon during their 2007
      migration through the Fraser River watershed in Canada. Chemical analyses
      revealed the presence of ppb to ppm levels of a wide variety of contaminants in
      these fish, including polychlorinated biphenyls (PCBs); polychlorinated dibenzo-p
      dioxins (PCDDs); polychlorinated dibenzofurans (PCDFs); polybrominated diphenyl
      ethers (PBDEs); organochlorine pesticides (OCPs) such as DDTs,
      hexachlorocyclohexanes (HCHs), octachlorostyrene, and cyclodienes; and Hg, As,
      Cd, Pb, and several other trace elements. Body weights and flesh lipid contents
      declined during upstream migration, resulting in significantly higher (p < 0.05)
      lipid-normalized concentrations of lipophilic organohalogens (PCBs, PCDD/Fs,
      pesticides) in those spawning salmon. Postmigration magnification factors (MFs)
      of organohalogens (0.1-10) were comparable to previous observations and model
      predictions. MFs generally increased with increasing hydrophobicity (K(OW)). For
      example, MFs of tetra- and pentachlorobenzenes and HCH isomers (log K(OW) range:
      3.8-5) were relatively low (between 0.1 and 1.7) compared with those of more
      lipophilic compounds (log K(OW) > 6) such as PCBs, DDTs, and mirex (MFs between 5
      and 10). Lipid-normalized muscle:egg ratios in female salmon, which varied
      between 0.1 and 8, also exhibited a positive relationship with chemical K(OW).
      The results indicate that lipophilic compounds (K(OW) > 10(6)) can be magnified
      in flesh lipids of Pacific salmon during spawning migration, but maternal
      transfer kinetics (deposition to eggs) of those chemicals are relatively slow
      compared with less hydrophobic compounds. 2,3,7,8-TCDD toxic equivalents
      (SigmaTEQs) in eggs of these spawning salmon, calculated using WHO toxic
      equivalency factors (WHO-TEFs) for fish health, in some cases exceeded the 0.3
      pg.g(-1) threshold level associated with 30% salmonid egg mortality, indicating
      the potential for reproductive impacts in Fraser River salmon populations.

PMID- 21086556
TI  - Prevention of recurrence after surgery for Crohn's disease: efficacy of
      infliximab.
AB  - After surgery for Crohn's disease (CD), early endoscopic lesions are frequently
      observed despite no symptomatic recurrence. The severity of lesions found at
      postoperative endoscopy is reported to be a strong predictive factor for future
      clinical recurrence. If endoscopic lesions in the early postoperative period can
      be reduced with medications, symptomatic recurrence will likely be delayed and
      decreased. Before the introduction of biologic therapies, various medications
      were used for the maintenance of clinical remission after surgery; however, few
      demonstrated consistent efficacy. Infliximab is a recombinant anti-tumor necrosis
      factor-alpha antibody. Although infliximab is one of the most effective
      medications in the management of CD, its efficacy for early endoscopic lesions
      after surgery has not yet been assessed. The author and colleagues recently
      conducted a prospective study in order to investigate the impact of infliximab on
      early endoscopic lesions after resection for CD. We found that infliximab therapy
      showed clear suppressive effects on clinical and endoscopic disease activity in
      patients with early endoscopic lesions after resection.

PMID- 21086555
TI  - Role of bacteria in carcinogenesis, with special reference to carcinoma of the
      gallbladder.
AB  - Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract
      cancer and is endemic in several countries. The interplay of genetic
      susceptibility, infections, and life style factors has been proposed to be
      responsible for carcinogenesis of gallbladder. Persistence of infection leading
      to chronic inflammation, and production of certain toxins and metabolites with
      carcinogenic potentials, by certain bacteria has been speculated to be involved
      in the transformation of the gallbladder epithelium. Therefore, any bacteria that
      have evolved to acquire both of the above carcinogenic mechanisms can cause
      cancer. Salmonella typhi has been found to be prominently associated with CaGB.
      Chronic typhoid carriage (persistence) and production of mediators of chronic
      inflammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also
      known for this bacterium. Furthermore, the natural concentrating function of the
      gallbladder might amplify the carcinogenic effect of the mediators of
      carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H.
      bilis and H. hepaticus) and Escherichia coli have also been implicated in
      carcinogenesis. As the isolation rate is very poor with the presently available
      culture techniques, the existence of bacteria in a viable but non-cultivable
      state is quite likely; therefore, sensitive and specific molecular techniques
      might reveal the etiological role of bacterial infection in gallbladder
      carcinogenesis. If bacteria are found to be causing cancers, then eradication of
      such infections might help in reducing the incidence of some cancers.

PMID- 21086557
TI  - Anatomy of the lateral ligaments of the rectum: a controversial point of view.
AB  - The existence and composition of the lateral ligaments of the rectum (LLR) are
      still the subjects of anatomical confusion and surgical misconception up to now.
      Since Miles proposed abdominoperineal excision as radical surgery for rectal
      cancer, the identification by "hooking them on the finger" has been accepted by
      many surgeons with no doubt; clamping, dividing and ligating are considered to be
      essential procedures in mobilization of the rectum in many surgical textbooks.
      But in cadaveric studies, many anatomists could not find LLR described by the
      textbooks, and more and more surgeons also failed to find LLR during the
      proctectomy according to the principle of total mesorectal excision. The anatomy
      of LLR has diverse descriptions in literatures. According to our clinical
      observations, the traditional anatomical structures of LLR do exist; LLR are
      constant dense connective bundles which are located in either lateral side of the
      lower part of the rectum, run between rectal visceral fascia and pelvic parietal
      fascia above the levator ani, and covered by superior fascia of pelvic diaphragm.
      They are pathways of blood vessels and nerve fibers toward the rectum and
      lymphatic vessels from the lower rectum toward the iliac lymph nodes.

PMID- 21086558
TI  - Monitoring early responses to irradiation with dual-tracer micro-PET in dual
      tumor bearing mice.
AB  - AIM: To monitor the early responses to irradiation in primary and metastatic
      colorectal cancer (CRC) with (18)F-fluorothymidine ((18)F-FLT) and (18)F
      fluorodeoxyglucose ((18)F-FDG) small-animal position emission tomography (micro
      PET). METHODS: The primary and metastatic CRC cell lines, SW480 and SW620, were
      irradiated with 5, 10 and 20 Gy. After 24 h, the cell cycle phases were analyzed.
      A dual-tumor-bearing mouse model of primary and metastatic cancer was established
      by injecting SW480 and SW620 cells into mice. micro-PET with (18)F-FLT and (18)F
      FDG was performed before and 24 h after irradiation with 5, 10 and 20 Gy. The
      region of interest (ROI) was drawn over the tumor and background to calculate the
      ratio of tumor to non-tumor (T/NT) in tissues. Immunohistochemical assay and
      Western blotting were used to examine the levels of integrin beta(3,) Ki-67,
      vascular endothelial growth factor receptor 2 (VEGFR2) and heat shock protein 27
      (HSP27). RESULTS: The proportion of SW480 and SW620 cells in the G(2)-M phase was
      decreased with an increasing radiation dose. The proportion of SW480 cells in the
      G(0)-G(1) phase was increased from 48.33% +/- 4.55% to 87.09% +/- 7.43% (P <
      0.001) and that of SW620 cells in the S-phase was elevated from 43.57% +/- 2.65%
      to 66.59% +/- 7.37% (P = 0.021). In micro-PET study, with increasing dose of
      radiation, (18)F-FLT uptake was significantly reduced from 3.65 +/- 0.51 to 2.87
      +/- 0.47 (P = 0.008) in SW480 tumors and from 2.22 +/- 0.42 to 1.76 +/- 0.45 (P =
      0.026) in SW620 tumors. (18)F-FDG uptake in SW480 and SW620 tumors was reduced
      but not significantly (F = 0.582, P = 0.633 vs F = 0.273, P = 0.845). Dose of
      radiation was negatively correlated with (18)F-FLT uptake in both SW480 and SW620
      tumors (r = -0.727, P = 0.004; and r = -0.664, P = 0.009). No significant
      correlation was found between (18)F-FDG uptake and radiation dose in SW480 or
      SW620 tumors. HSP27 and integrin beta(3) expression was higher in SW480 than in
      SW620 tumors. The T/NT ratio for (18)F-FLT uptake was positively correlated with
      HSP27 and integrin beta(3) expression (r = 0.924, P = 0.004; and r = 0.813, P =
      0.025). CONCLUSION: (18)F-FLT is more suitable than (18)F-FDG in monitoring early
      responses to irradiation in both primary and metastatic lesions of colorectal
      cancer.

PMID- 21086560
TI  - Absence of high amplitude propagating contractions in subjects with chronic
      spinal cord injury.
AB  - AIM: To investigate the presence or absence of high amplitude propagating
      contractions (HAPC), as well as the other measures of colonic motility, in
      persons with spinal cord injury (SCI). METHODS: Prolonged colonic ambulatory
      manometric studies were performed on 14 male volunteers: 8 with SCI (mean age, 59
      +/- 13 years; mean duration of injury, 13 +/- 4 years) and 6 healthy able-bodied
      controls (mean age, 57 +/- 10 years). A solid-state manometry catheter was
      endoscopically clipped to the splenic flexure. Recording was performed for > 24 h
      after manometric catheter placement. RESULTS: HAPC were absent in individuals
      with SCI during pre-sleep, sleep, and post-sleep phases. HAPC were significantly
      increased after awakening in non-SCI controls (0.8 +/- 0.2 HAPC/h vs 10.5 +/- 2.0
      HAPC/h, P < 0.005). The motility index was lower in those with SCI than in
      controls pre- and post-sleep (SCI vs non-SCI: Pre-sleep, 2.4 +/- 0.4 vs 8.8 +/-
      1.9, P < 0.01; Post-sleep, 4.3 +/- 0.8 vs 16.5 +/- 4.5, P < 0.05). However, a
      sleep-induced depression of colonic motility was observed in both the SCI and non
      SCI groups (Pre-sleep vs Sleep, non-SCI: 8.8 +/- 1.9 vs 2.1 +/- 0.9, P < 0.002;
      SCI: 2.4 +/- 0.4 vs 0.2 +/- 0.03, P < 0.001), with the motility index of those
      with SCI during sleep not significantly different than that of the controls.
      CONCLUSION: HAPC were not observed in individuals with SCI pre- or post-sleep. A
      sleep-induced depression in general colonic motility was evident in SCI and
      control subjects.

PMID- 21086559
TI  - Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury and
      represents a potential therapeutic target.
AB  - AIM: To evaluate the role of leptin in the internal disorders during hepatic
      ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic
      ischemia/reperfusion injury was established, with groups of sham-operation
      (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and
      I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum
      glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and
      diamine oxidase were determined by relevant kits, while histological alterations
      and protein levels of leptin in the lung, liver and duodenum were examined by
      hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation
      between leptin and other variables or grading of tissue impairment were analyzed
      simultaneously. RESULTS: Serum leptin in I60'R360' was significantly higher than
      in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was
      higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation
      capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and
      I60'R150'groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and
      I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine
      transaminase in the four reperfusion groups were higher than in the Sham group
      (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P <
      0.05). Histological impairment in the lung, liver and duodenum at the early phase
      of this injury was more serious, but the impairment at the later phase was
      lessened gradually. Protein levels of leptin in the lung in the four reperfusion
      groups were significantly lower than in the Sham group (all P < 0.01), decreasing
      in the order of I60'R150', I60'R60', I60'R360' and I60'R240'; the levels in the
      liver in I60'R60' and I60'R240' were higher than in the Sham group (both P <
      0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60'
      (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher
      than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150'
      was lower than in I60'R60' (P < 0.05). There was a significantly positive
      correlation between serum leptin and alanine transaminase (rho = 0.344, P =
      0.021), a significantly negative correlation between the protein level of leptin
      in the lung and its damage scores (rho = -0.313, P = 0.036), and a significantly
      positive correlation between the protein level of leptin in the liver and its
      damage scores (rho = 0.297, P = 0.047). CONCLUSION: Endogenous leptin fluctuates
      in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the
      internal disorders and represents a potential target for supportive therapy.

PMID- 21086561
TI  - Cortical and spinal evoked potential response to electrical stimulation in human
      rectum.
AB  - AIM: To study a novel technique to record spinal and cortical evoked potentials
      (EPs) simultaneously in response to electrical stimulation in the human rectum.
      METHODS: Eight male and nine female healthy volunteers participated. Stimulating
      electrodes were attached to the rectal mucosa at 15 cm and 12 cm above the
      dentate line. Recording skin electrodes were positioned over vertebrae L4 through
      S2. The electrical stimulus was a square wave of 0.2 ms duration and the
      intensity of the stimulus varied between 0 and 100 mA. EP responses were recorded
      using a Nicolet Viking IV programmable signal conditioner. RESULTS: Simultaneous
      recording of cortical and spinal EPs was obtained in > 80% of the trials. The EP
      responses increased with the intensity of the electrical stimulation, were
      reproducible overtime, and were blocked by application of Lidocaine jelly at the
      site of stimulation. The morphology (N1/P1), mean +/- SD for latency (spinal N1,
      4.6 +/- 0.4 ms; P1, 6.8 +/- 0.5 ms; cortical N1, 136.1 +/- 4.2 ms; P1, 233.6 +/-
      12.8 ms) and amplitude (N1/P1, spinal, 38 +/- 7 MUV; cortical 19 +/- 3 MUV) data
      for the EP responses were consistent with those in the published literature.
      Reliable and reproducible EP recordings were obtained with the attachment of the
      electrodes to the rectal mucosa at predetermined locations between 16 and 8 cm
      above the anal verge, and the distance between the attachment sites of the
      electrodes (the optimal distance being approximately 3.0 cm between the two
      electrodes). CONCLUSION: This technique can be used to assess potential
      abnormalities in primary afferent neural pathways innervating the rectum in
      several neurodegenerative and functional pain disorders.

PMID- 21086562
TI  - Entecavir as treatment for reactivation of hepatitis B in immunosuppressed
      patients.
AB  - AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy
      for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four
      patients that were treated with different immunosuppressive regimens for
      hematological malignancies, who presented with HBV reactivation were treated with
      ETV. Clinical outcome, biochemical and virological factors, including
      quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all
      patients, ETV induced suppression of HBV, and rapid clinical improvement without
      side effects. In one patient with an alanine aminotransferase (ALT) flare,
      tenofovir was added after 3 mo of treatment. Until death from disease progression
      at 6 mo after treatment initiation, this patient did not clear HBV infection.
      Retrospectively, it is highly probable that the patient had been non-adherent. In
      the other three patients, the virological responses were associated with an
      expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and
      all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau
      after 3 mo, before becoming undetectable after 1 year, despite early ALT
      normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be
      effective and safe treatment for HBV reactivation. Monitoring of quantitative
      HBsAg might be an additional useful tool to monitor treatment response.

PMID- 21086563
TI  - Endotics system vs colonoscopy for the detection of polyps.
AB  - AIM: To compare the endotics system (ES), a set of new medical equipment for
      diagnostic colonoscopy, with video-colonoscopy in the detection of polyps.
      METHODS: Patients with clinical or familial risk of colonic polyps/carcinomas
      were eligible for this study. After a standard colonic cleaning, detection of
      polyps by the ES and by video-colonoscopy was performed in each patient on the
      same day. In each single patient, the assessment of the presence of polyps was
      performed by two independent endoscopists, who were randomly assigned to
      evaluate, in a blind fashion, the presence of polyps either by ES or by standard
      colonoscopy. The frequency of successful procedures (i.e. reaching to the cecum),
      the time for endoscopy, and the need for sedation were recorded. Sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      of the ES were also calculated. RESULTS: A total of 71 patients (40 men, mean age
      51.9 +/- 12.0 years) were enrolled. The cecum was reached in 81.6% of ES
      examinations and in 94.3% of colonoscopies (P = 0.03). The average time of
      endoscopy was 45.1 +/- 18.5 and 23.7 +/- 7.2 min for the ES and traditional
      colonoscopy, respectively (P < 0.0001). No patient required sedation during ES
      examination, compared with 19.7% of patients undergoing colonoscopy (P < 0.0001).
      The sensitivity and specificity of ES for detecting polyps were 93.3% (95% CI: 68
      98) and 100% (95% CI: 76.8-100), respectively. PPV was 100% (95% CI: 76.8-100)
      and NPV was 97.7% (95% CI: 88-99.9). CONCLUSION: The ES allows the visualization
      of the entire colonic mucosa in most patients, with good sensitivity/specificity
      for the detection of lesions and without requiring sedation.

PMID- 21086564
TI  - Incidence of congenital hemolytic anemias in young cholelithiasis patients.
AB  - AIM: To clarify the incidence of congenital hemolytic anemias (CHA) in young
      cholelithiasis patients and to determine a possible screening test based on the
      results. METHODS: Young cholelithiasis patients (< 35 years) were invited to our
      outpatient clinic. Participants were asked for comorbidities and family history.
      The number of gallstones were recorded. Blood samples were obtained to perform a
      complete blood count, standard Wright-Giemsa staining, reticulocyte count,
      hemoglobin (Hb) electrophoresis, serum lactate dehydrogenase and bilirubin
      levels, and lipid profile. RESULTS: Of 3226 cholecystectomy patients, 199 were
      under 35 years, and 190 with no diagnosis of CHA were invited to take part in the
      study. Fifty three patients consented to the study. The median age was 29 years
      (range, 17-35 years), 5 were male and 48 were female. Twelve patients (22.6%)
      were diagnosed as thalassemia trait and/or iron-deficiency anemia. Hb levels were
      significantly lower (P = 0.046), and mean corpuscular volume (MCV) and hematocrit
      levels were slightly lower (P = 0.072 and 0.082, respectively) than normal. There
      was also a significantly lower number of gallstones with the diagnosis (P =
      0.007). CONCLUSION: In endemic regions, for young cholelithiasis patients (age
      under 35) with 2-5 gallstones, the clinician/surgeon should pay attention to MCV
      and Hb levels as indicative of CHA.

PMID- 21086565
TI  - Traction-assisted endoscopic mucosal resection for polypectomy in the large
      intestine.
AB  - AIM: To evaluate if traction-assisted endoscopic mucosal resection (TA-EMR) is
      feasible and if it enables en bloc resection of colorectal lesions. METHODS:
      Seven patients with a total of 12 colorectal adenomas were prospectively
      enrolled. All lesions were removed by TA-EMR: one hemostatic clip tied to a white
      silk suture was applied to the base of the lesion to allow traction through the
      working channel of the colonoscope. A conventional polypectomy snare was mounted
      over the suture and the lesion was pulled into the snare and resected in one
      piece. RESULTS: All 12 lesions (nine sessile) were resected en bloc with free
      lateral and vertical margins by using this novel technique, including five
      lesions (5/12, 41.6%) in less-accessible positions, where TA-EMR enabled complete
      visualization of the base before resection. Mean longest lesion and specimen
      sizes were 9 mm (range: 6-25 mm) and 11 mm in diameter (range: 7-17 mm),
      respectively. No serious procedure-related complications were observed.
      CONCLUSION: TA-EMR through the endoscope using a hemostatic clip and suture
      material is technically feasible. Visualization of colorectal lesions in less
      accessible locations can be improved.

PMID- 21086566
TI  - Increased osteopontin and liver stiffness measurement by transient elastography
      in biliary atresia.
AB  - AIM: To analyze plasma osteopontin levels and liver stiffness using transient
      elastography in postoperative biliary atresia (BA) children compared with healthy
      controls. METHODS: Thirty children with postoperative BA and 10 normal controls
      were enrolled. The patients were categorized into two groups according to their
      jaundice status. Plasma levels of osteopontin were determined using commercially
      available enzyme-linked immunosorbent assay. Liver stiffness was measured by
      using transient elastography (Fibroscan). Ten validated Fibroscan measurements
      were performed in each patient and control with the result expressed in
      kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA
      children compared with that of healthy controls (47.0 +/- 56.4 ng/mL vs 15.1 +/-
      15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in
      the patients with BA compared with that of controls (26.9 +/- 24.6 kPa vs 3.9 +/-
      0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice
      had more pronounced plasma osteopontin levels than those without jaundice (87.1
      +/- 61.6 ng/mL vs 11.9 +/- 6.1 ng/mL, P = 0.001). Furthermore, the mean liver
      stiffness was significantly greater in the jaundiced BA patients compared with
      non-jaundiced patients (47.7 +/- 21.8 kPa vs 8.7 +/- 3.0 kPa, P = 0.001).
      Additionally, plasma osteopontin was positively related to serum total bilirubin
      (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin
      and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma
      osteopontin positively correlated with degree of hepatic fibrosis and could be
      used as a biochemical parameter reflecting disease severity in postoperative BA
      children.

PMID- 21086567
TI  - Evaluation of non-ampullary duodenal polyps: comparison of non-neoplastic and
      neoplastic lesions.
AB  - AIM: To evaluate duodenal polyps, divided into non-neoplastic and neoplastic
      lesions. In addition, the clinical characteristics of duodenal hyperplastic
      polyps are determined. METHODS: We analyzed medical records of 50,114 consecutive
      patients submitted to for first diagnostic esophago-gastroduodenoscopy between
      January 2004 and December 2009. We excluded lesions on the ampulla of Vater and
      submucosal tumors. We studied 510 cases that were diagnosed endoscopically with
      duodenal polyps and enrolled a total of 221 cases that had undergone tissue
      biopsy. We analyzed the differences between non-neoplastic and neoplastic
      lesions, and determined the clinical features of duodenal hyperplastic polyps.
      RESULTS: Non-neoplastic lesions were found in 196 patients and neoplastic lesions
      in 25 patients. On univariate analysis, there were significant differences in
      shape, location, and size. Polyps more than 10 mm in diameter or polyps in the
      second portion had independent risk factors for being neoplastic lesions, as
      identified by multivariate analysis. In 23 cases of hyperplastic polyps (79.3%),
      they were accompanied by gastro-duodenal pathology, which was possibly associated
      with Helicobacter pylori. CONCLUSION: Polyps of more than 10 mm or polyps in the
      second portion of the duodenum should be evaluated by histological examination.

PMID- 21086568
TI  - Brain activity following esophageal acid infusion using positron emission
      tomography.
AB  - AIM: To investigate symptoms and brain activity following esophageal acid
      infusion. METHODS: Fifteen healthy volunteers were recruited for the study.
      Hydrochloric acid (pH 1 and 2) and distilled water (pH 7) were randomly and
      repeatedly infused into the esophagus. The brain activity was evaluated by
      positron emission tomography. The severity of heartburn elicited by the infusion
      was rated on an auditory analog scale of 0-10. RESULTS: The severity of heartburn
      following each infusion showed a step-wise increase with increasing acidity of
      the perfusate. The heartburn scores were significantly higher in the second pH 1
      infusion compared with the first infusion. Acid and distilled water infusion
      induced activation of various brain areas such as the anterior insula, temporal
      gyrus, and anterior/posterior cingulate cortex. At pH 1 or 2, in particular,
      activation was observed in some emotion-related brain areas such as the more
      anterior part of the anterior cingulate cortex, parahippocampal gyrus, or the
      temporal pole. Strong activation of the orbitofrontal cortex was found by
      subtraction analysis of the two second pH 1 infusions, with a significant
      increase of heartburn symptoms. CONCLUSION: Emotion-related brain areas were
      activated by esophageal acid stimulation. The orbitofrontal area might be
      involved in symptom processing, with esophageal sensitization induced by repeated
      acid stimulation.

PMID- 21086569
TI  - Predictors of rebleeding after initial hemostasis with epinephrine injection in
      high-risk ulcers.
AB  - AIM: To identify the predictors of rebleeding after initial hemostasis with
      epinephrine injection (EI) in patients with high-risk ulcers. METHODS: Recent
      studies have revealed that endoscopic thermocoagulation, or clips alone or
      combined with EI are superior to EI alone to arrest ulcer bleeding. However, the
      reality is that EI monotherapy is still common in clinical practice. From October
      2006 to April 2008, high-risk ulcer patients in whom hemorrhage was stopped after
      EI monotherapy were studied using clinical, laboratory and endoscopic variables.
      The patients were divided into 2 groups: sustained hemostasis and rebleeding.
      RESULTS: A total of 175 patients (144, sustained hemostasis; 31, rebleeding) were
      enrolled. Univariate analysis revealed that older age (>= 60 years), advanced
      American Society of Anesthesiology (ASA) status (category III, IV and V), shock,
      severe anemia (hemoglobin < 80 g/L), EI dose >= 12 mL and severe bleeding signs
      (SBS) including hematemesis or hematochezia were the factors which predicted
      rebleeding. However, only older age, severe anemia, high EI dose and SBS were
      independent predictors. Among 31 rebleeding patients, 10 (32.2%) underwent
      surgical hemostasis, 15 (48.4%) suffered from delayed hemostasis causing major
      complications and 13 (41.9%) died of these complications. CONCLUSION: Endoscopic
      EI monotherapy in patients with high-risk ulcers should be avoided. Initial
      hemostasis with thermocoagulation, clips or additional hemostasis after EI is
      mandatory for such patients to ensure better hemostatic status and to prevent
      subsequent rebleeding, surgery, morbidity and mortality.

PMID- 21086570
TI  - Gastric juice acidity in upper gastrointestinal diseases.
AB  - AIM: To search the independent factors determining gastric juice acidity and to
      investigate the acidity of gastric juices in various benign and malignant upper
      gastrointestinal diseases. METHODS: Fasting gastric juice acidity of 165 healthy
      subjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n =
      136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and
      compared. Additionally, gastric specimens were taken from the antrum and body for
      rapid urease test and histological examination. RESULTS: Multivariate analysis
      revealed that bile stain of gastric juice, high acute inflammatory score of the
      corpus, and atrophy of the corpus were independent risk factors for the
      development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1
      (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer
      patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric
      juices than healthy subjects. In contrast, gastric ulcer and gastric cancer
      patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy
      controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects,
      esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients,
      respectively. CONCLUSION: Bile reflux, atrophy and dense neutrophil infiltrate of
      the corpus are three independent factors determining the acidity of gastric
      juice.

PMID- 21086571
TI  - FOXP3 expression and clinical characteristics of hepatocellular carcinoma.
AB  - AIM: To study the biological and clinical characteristics of transcription factor
      forkhead box protein 3 (FOXP3) in hepatocellular carcinoma (HCC). METHODS: We
      analyzed the expression and localization of FOXP3 in HCC tissues and cell lines
      to evaluate its biological features. The relationship between FOXP3 staining and
      clinical risk factors of HCC was assessed to identify the clinical
      characteristics of FOXP3 in HCC. RESULTS: The mRNA and protein expression of
      FOXP3 were found in some hepatoma cell lines. Immunohistochemical (IHC) analysis
      of HCC sections revealed that 48% of HCC displayed FOXP3 staining, but we did not
      find any FOXP3 staining in normal liver tissues and para-tumor tissues. IHC and
      Confocal analysis showed that the expressions of FOXP3 were mainly present in the
      nucleus and cytoplasm of tumor cells in tissues or cell lines. In HCC, the
      distribution of FOXP3 was similar to that of the cirrhosis, but not to the
      hepatitis B virus. Those findings implicate that FOXP3 staining seems to be
      associated with the high risk of HCC. CONCLUSION: The clinical characteristics of
      FOXP3 in HCC warrants further studies to explore its functions and roles in the
      cirrhosis and development of HCC.

PMID- 21086572
TI  - Cyclooxygenase-2 polymorphisms and susceptibility to gastric carcinoma: a meta
      analysis.
AB  - AIM: To investigate the association of the cyclooxygenases-2 (COX-2)
      polymorphisms and susceptibility to gastric cancer (GC) by means of meta
      analysis. METHODS: Publications addressing the association between polymorphisms
      of COX-2 and susceptibility to GC were selected from the MEDLINE, EMBASE and
      CBMdisc databases. Data was extracted from the studies by 2 independent
      reviewers. The meta-analyses were performed by RevMan 5.0.23. From these data,
      odds ratio (OR) with 95% confidence interval (CI) was calculated. RESULTS: Ten
      studies were retrieved reporting a total of 11 COX-2 polymorphisms. Carriers of 
      765C, -1195A, -1290G, *2430T alleles and *429TT genotype revealed increased risk
      for GC (OR = 1.71, 95% CI: 1.01-2.90, P = 0.05; OR = 1.58, 95% CI: 1.05-2.38, P =
      0.03; OR = 1.55, 95% CI: 1.01-2.39, P = 0.05; OR = 2.62, 95% CI: 1.20-5.73, P =
      0.02 and OR = 0.74, 95% CI: 0.59-0.95, P = 0.02, respectively). CONCLUSION: The 
      765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms
      were determined a significant association with susceptibility to GC.

PMID- 21086573
TI  - Sirolimus plus sorafenib in treating HCC recurrence after liver transplantation:
      a case report.
AB  - A case of hepatocellular carcinoma (HCC) with pulmonary recurrence after liver
      transplantation for HCC is presented in this report. The patient showed disease
      progression on sorafenib therapy demonstrated by computed tomography scans as
      well as serial serum alpha-fetoprotein (AFP) elevation. After his
      immunosuppression therapy was successfully transitioned to sirolimus and a
      continuation of sorafenib, he achieved partial remission based on RECIST criteria
      and normalization of AFP. Mammalian target of rapamycin inhibitors including
      sirolimus alone or in conjunction with sorafenib may be useful in the treatment
      of post transplant HCC.

PMID- 21086576
TI  - [Image of the month. Recurrent hemangioma of skeletal muscle].

PMID- 21086577
TI  - [How I treat...paroxysmal narrow complex QRS tachycardia].
AB  - Paroxysmal narrow complex QRS tachycardias are a clinical entity characterized by
      abrupt onset and termination of palpitations, dyspnea, dizziness. They depend on
      mechanisms of reentry within the atrio-ventricular node or with the participation
      of an accessory pathway (reciprocating orthodromic tachycardia). We review the
      clinical and electrocardiographical diagnosis as well as the acute and long term
      treatment of these tachycardias.

PMID- 21086579
TI  - [Sulfonylureas dosage: from therapeutic monitoring to differential diagnosis of
      hyperinsulinism].
AB  - More than fifty years after their marketing, sulfonylureas remain one of the most
      prescribed drugs for the treatment of non-insulino-dependent diabetes mellitus.
      However, these products are sometimes responsible of unexplained and severe
      hypoglycaemias observed in patient without diabetic pathology. These typical
      hypoglycemias, qualified as factious, are one of the clinical expressions of the
      Munchausen syndrome, a psychiatric disorder characterized by the need for the
      subject to simulate a pathology. The hypoglycemia is associated with an
      endogenous hyperinsulinism, also observed in a rare endocrine pathology, the
      insulinoma. This article aims to show the interest of the determination of
      sulfonylureas in blood for the differential diagnostic of endogenous
      hyperinsulinisms. The confirmation of a factious hypoglycemia is capital to avoid
      a partial or subtotal pancreatectomy, surgical treatment when an insulinoma is
      suspected. Ultra liquid chromatography coupled with the mass spectrometry tandem
      (UPLC-MS-MS) technique had been used. The technique allowed the identification
      and quantification of the most used sulfonylureas and repaglinide in blood, and
      will be a method of choice to confirm a non-appropriate consumption of
      sulfonylureas.

PMID- 21086578
TI  - [Malignant peritoneal mesothelioma: a case report].
AB  - I report two cases of malignant peritoneal mesothelioma. Mesothelioma is mostly a
      pleural disease whether visceral or parietal. Infra-diaphragmatic Mesothelioma
      accounts for only 10-20% of all mesotheliomas. In over 80% of the cases the
      pathogenesis is related to asbestos and radiation exposure. However cases with no
      past history of such exposures appear in the literature. One of our two patients
      has non past history of exposure to asbestos. In both cases the diagnosis was
      establishes through both biopsy conducted by laparoscopy and ascites fluid
      cytology. The disease is most common in males over the age of 40. In case of
      localised disease cytoreductive surgery using hyperthermic intraperitoneal
      chemotherapy is recommended. Sadly the disease is often unveiled at an advanced
      stage requiring palliative chemotherapy usually with a platin derivative or in a
      small percentage of the cases with abdominal radiotherapy to alleviate pain.
      Prognosis for patients with malignant peritoneal mesothelioma is very poor with a
      mean survival of 5,4 months versus 12.5 months for pleural mesothelioma.
      Peritoneal mesothelioma, although rare, should be considered among the
      differential diagnosis of ascites differential diagnosis work up.

PMID- 21086580
TI  - [The endocrine effects of smoking].
AB  - Almost one third of men and women smoke in Belgium. Besides the well known
      tobacco's neck and cardiopulmonary systems adverse effects as well as associated
      neoplasms, today we recognize other deleterious consequences of tobacco on the
      neuroendocrine, thyroid and reproductive systems. Not only active smokers but
      also the fetus carried by a smoking mother is at risk for important health
      problems. Tobacco is a recognized risk factor of occurrence of ophtalmopathy.
      Some of the active components of tobacco as the thiocyanates are goitrogenic.
      Tobacco is a risk factor for men and women's infertility. Newborns from parents
      that smoke are at risk for sudden death. These consequences represent a major
      public health issue. A campaign for smoking cessation has been recently launched
      by the Federation of Public Health Service and the INAMI in Belgium.

PMID- 21086581
TI  - [Hurting the "black, yellow, red" dogma of leg ulcers].
AB  - The medical history of a leg ulcer is spangled with episodes contributing to its
      chronicity before leading to possible healing. The complexity of the involved
      biological factors is undisputable. In order to simplify the management of these
      lesions, some doctors and nurses summarize the evolution of a leg ulcer in 3
      phases according to the colour of the wound bed: black, yellow and red. The
      latter stage is commonly considered as a favourable condition for skin healing.
      We criticize such a concept by showing the anatomo-functional heterogeneity of
      the red wound bed.

PMID- 21086582
TI  - [Pyoderma gangrenosum: 6 cases].
AB  - Pyoderma gangrenosum (PG) is an uncommon extensive cutaneous ulceration belonging
      to the neutrophilic disease spectrum. It is associated to a systemic disease in
      almost 50% of cases. The diagnosis primarily relies on clinico-pathological
      features and the treatment is empirical. We report a retrospective series of 6
      observations of PG (4 women and 2 men, median age = 43 years) enrolled over 15
      years. The diagnosis was established based on the presence of 2 major criteria
      and 2 minor criteria of the disease. In 3 patients, PG was associated to an
      already known ulcerative colitis. The treatment consisted in general
      corticotherapy.

PMID- 21086583
TI  - [Puerperal uterine inversion].
AB  - The uterine inversion defines itself anatomically as the invagination of the
      uterine bottom "finger of glove" until be able to at most express itself in the
      vulva. It is a dramatic accident of the delivery and a sporadic occurrence in
      countries with low medical entity, this rarity which can mislead the
      practitioner, the delay of the diagnosis ends in redoubtable complications even
      the maternal death. Through a retrospective study concerning six case reports
      brought together within CHU Hassan II of Fez spreading out over eight years and
      review of literature, we try to describe different aspects epidemiological,
      etiologic, therapeutic and prognosis of this rather particular entity.

PMID- 21086584
TI  - [Sarcopenia: a physical marker of frailty].
AB  - Sarcopenia is defined by loss of muscular mass, strength and quality that occur
      in elderly. Multiple factors underlie this process: low physical activity, low
      steroids hormones, increase of cytokines, loss of motoneurons, decrease of
      protein synthesis...However, the role of these factors is not yet well understood
      and consensual clinical definition and assessment are still needed. It has become
      an important area of research because of its frequency and the influence in the
      disability of old people. It is a major component of frailty. So far, no
      pharmacological treatment has proven definitive evidence to treat or prevent
      sarcopenia. Nevertheless, it needs a multidimensional approach based on physical
      activity and prevention of malnutrition.

PMID- 21086585
TI  - [How I explore...skin by photodiagnosis using skin fluorescence and its
      functional imaging].
AB  - Under specific light illumination, skin produces peculiar fluorescent aspects.
      Such property can be used to provide diagnostic arguments or to disclose some
      peculiar functions of the skin. Some superficial infections (erythrasma, tinea
      versicolor, dermatophytic tinea,..) reveal fluorescence that may be intense. The
      pilosebaceous follicles enriched in Propionibacterium spp show fluorescence. Such
      property is lost during some anti-acne treatments. A quenching effect is observed
      after application of sunscreens. The (pre)neoplastic areas prepared for dynamic
      phototherapy become fluorescent. Pyranine labeling of the stratum corneum
      exhibits fluorescence allowing the assessment of the renewal activity of the
      epidermis.

PMID- 21086587
TI  - [Clinical study of the month. Accord-lipid and accord-eye: towards a new
      positioning of fenofibrate in the management of type 2 diabetes].
AB  - Fenofibrate has been evaluated in the ACCORD trial, in combination with a statin,
      to prevent vascular complications in patients with type 2 diabetes. In ACCORD
      Lipid, the addition of fenofibrate was not able to significantly reduce the
      incidence of a composite cardiovascular endpoint (no positive effect was also
      observed with the intensification of blood glucose or blood pressure control in
      this population). However, an interaction effect was observed according to basal
      lipid profile, suggesting a better protection by fenofibrate in patients with
      hypertriglyceridaemia and low HDL cholesterol (so-called atherogenic
      dyslipidaemia). In ACCORD-Eye, the addition of fenofibrate to a basal statin
      therapy resulted in a significant reduction of the progression of diabetic
      retinopathy, in a similar manner as that observed with intensifying blood glucose
      control (but with a good safety profile and without increasing the risk of
      hypoglycaemia). These observations, confirming earlier results from FIELD also
      with this fibrate, open new perspectives for a useful prescription of fenofibrate
      in patients with type 2 diabetes.

PMID- 21086586
TI  - [Saxagliptin (Onglyza): new inhibitor of the dipeptidylpeptidase-4 for the oral
      treatment of type 2 diabetes].
AB  - Saxagliptin (Onglyza) is a specific and reversible inhibitor of
      dipeptidylpeptidase-4 (DPP-4), which inhibits the activity of the enzyme for at
      least 24 hours after one single oral administration. It increases the circulating
      levels of incretin hormones (GLP-1, GIP), which contributes to amplify the
      insulin secretory response to meals and to reduce postprandial hyperglycaemia
      and, subsequently, fasting glycaemia. Saxagliptin, 5 mg once daily, has been
      shown to be effective in patients with type 2 diabetes treated with diet alone,
      metformin, sulfonylurea or glitazone, with a favourable tolerance profile.
      Reduction in glycated haemoglobin (HbA(1c)) averaged 0.6-0.8%, without increasing
      the risk of hypoglycaemia or promoting weight gain. The only indication of
      saxagliptin that is currently reimbursed in Belgium is the treatment of patients
      not controlled with metformin, the oral antidiabetic agent that is recommended as
      first line therapy in the management of type 2 diabetes.

PMID- 21086588
TI  - [Dynamics of postural dysfunction in patients with Parkinson's disease under the
      action of vibrational therapy].
AB  - This experimental study was designed to reveal changes of the postural function
      in patients with Parkinson's disease (PD) under the action of vibrational
      therapy. It was shown that application of classical passive vibrostimulation
      employed under clinical conditions can be recommended to patients presenting with
      the rigid-trembling form of Parkinson's disease owing to the fact that their
      system of regulation of the vertical posture readily responds to vibration
      loading. This effect is attributable to low muscular activity.

PMID- 21086589
TI  - [The effect of different regimes of motor activity on age-specific dynamics of
      the main functional systems of the organism].
AB  - The present study included 229 healthy men having different habitual patterns of
      daily locomotor activity. They were allocated to 4 groups encompassing subjects
      of different age. Group 1 consisted of medium-level athletes and subjects
      regularly engaged in physical exercises, group 2 included former high-level
      athletes continuing active physical training, group 3 was comprised of former
      high-level athletes living a sedentary life style, and group 4 included subjects
      who were never engaged in physical exercises. All the participants of the study
      were examined using an AMSAT-COVERT automated diagnostic system designed for
      rapid topical evaluation of the human functional state. The results of the study
      indicate that the regime of daily locomotor activity and previous experience with
      physical training have marked effect on the age-specific dynamics of the main
      functional systems of the organism. Continuation of physical activity in former
      athletes permits them to preserve a higher functional status of the main
      functional systems of the organism compared with former high-level athletes
      living a sedentary life style and subject who were never engaged in physical
      exercises.

PMID- 21086590
TI  - [Application of the pulsed low-frequency electrostatic field in the early
      rehabilitative treatment of patients following surgery for the correction of
      valgus deformation of the first toe].
AB  - This paper describes the method and results of application of the pulsed low
      frequency electrostatic field (PLFESF) to the lower extremities of the patients
      who underwent surgical treatment for the correction of valgus deformation of the
      first toe. The efficiency of the method used in the early period of
      rehabilitative treatment was estimated at 93.3% compared with 96.7% in the
      patients who were managed by the same therapy in combination with polyoxdonium.

PMID- 21086591
TI  - [The use of magnetic-laser therapy in the combined treatment of osteoarthrosis in
      workers exposed to inorganic fluoride compounds].
AB  - The present study included 67 patients who had been exposed to the impact of
      inorganic fluoride compounds. It demonstrated beneficial effect of magnetolaser
      therapy in combination with whole body iodine-bromide-sodium chlorine baths,
      physical exercises, and massage on clinical manifestations of the primary disease
      and concomitant pathologies. Simultaneously, metabolic processes in the articular
      cartilage and bone tissue were normalized, lipid peroxidation was improved and
      optimization of antioxidative protection achieved. These changes are indicative
      of high therapeutic efficiency of the combined treatment employed in this study
      and its favourable influence on the quality of life of the patients.

PMID- 21086592
TI  - [Combined application of electric myo-stimulation and meso-therapy for the
      correction of age-related changes of the facial skin].
AB  - The objective of the present study was to evaluate effects of mesotherapy (MT)
      and electrostimulation (EMS) on age-related changes of the facial skin. The
      secondary objective was to identify factors influencing the therapeutic
      efficiency of these methods. The study included 60 women aged from 30 to 59
      years. All the patients were examined prior to the onset and in the end (after
      one month) of the corrective treatment. Facial skin conditions were assessed
      using a Skin XP Pro system and skin microcirculation by laser Doppler flowmetry
      (LDF). The psychological status of the patients was evaluated with the help of
      the Well-being-Activity-Mood test. After the primary examination, the
      participants of the study were randomly divided into two groups. Group 1 (n=30)
      included women treated by MT and EMS, the control group 2 (n=30) was comprised of
      the patients who did not receive the above treatment. The results of the study
      indicate that combine MT + EMS therapy significantly improves the state of facial
      skin, decreases its pigmentation, reduces the number and depth of wrinkles,
      enhances skin moisture, improves its elasticity and decreases porosity. Dynamics
      of these parameters and overall effect of correction were shown to correlate with
      the severity of skin changes before the treatment. Age-related changes in the
      facial skin were especially well-apparent in women with the lowered activity
      level and impaired mood. Characteristics of mood in the course of therapeutic
      correction correlated with dynamics of skin smoothness and elasticity.

PMID- 21086593
TI  - [Application of physical therapeutic techniques for the improvement of the
      efficacy of dental implantation].
AB  - This study included 230 patients presenting with defects of tooth alignments. It
      has demonstrated that the physiotherapeutic treatment before and after dental
      implantation using a KAP-Parodontolog stomatological system markedly improved the
      outcome of implantation.

PMID- 21086594
TI  - [Rehabilitative treatment of metabolic syndrome in a sanatorium].
AB  - This study included 386 patients with metabolic syndrome admitted for the
      treatment to a health spa facility. Diagnosis was established using the specially
      developed program of combined clinical examination, functional tests, and
      laboratory analyses. A specific feature of the present spa and resort treatment
      was the extensive application of carefully selected non-medicinal therapeutic
      modalities in combination with pharmaceutical preparations. The study has
      demonstrated that the use of the active treatment program produced beneficial
      effect in the majority of the patients.

PMID- 21086595
TI  - [Chrono- and reflexotherapy for the treatment of the biliary tract dysfunctions].
AB  - The objective of this work was to develop a scientifically sound rationale for
      the method of reflex correction of biliary tract dysfunction based on
      chronobiological data concerning functioning of the acupuncture points
      corresponding to biliary ducts. It was shown that patients presenting with
      biliary dyskinesia (i.e., forming desynchronism) experience a shift of both skin
      temperature and electrical resistance at the acupuncture points. The
      chronoreflexotherapeutic technique employed in this study makes it possible to
      rapidly restore disturbed biorhythms of functioning of the biliary system,
      normalize the motor-evacuating activity of the gallbladder, and eliminate
      clinical manifestations of the disease.

PMID- 21086596
TI  - [The use of microwave resonance therapy in the combined treatment of chronic
      pyelonephritis].
AB  - The inclusion of microwave resonance therapy with 'fluctuating' frequency and a
      varied wave range in the combined treatment of patients with chronic
      pyelonephritis is well-founded pathogenetically since this method allows for the
      correction of lipid peroxidation level and parameters of the prooxidative
      antioxidative activity in the blood serum. Moreover, it has beneficial effect on
      regulation of physico-chemical properties of biological membranes.

PMID- 21086598
TI  - [The use of air cryotherapy for the rehabilitative treatment of patients with
      osteoarthrosis and soft-tissue diseases. Ministry of Health and Social
      Development of Russian Federation. Russian Scientific Center of Rehabilitation
      Medicine and Balneology ].

PMID- 21086597
TI  - [Modern technologies for extraction of balneological medicines from mineral
      waters].
AB  - A new technology for isolation of medicinal balneological preparations from
      mineral waters has been developed. It is based on the extraction of biologically
      active compounds (BAC) from mineral waters with ethanol following oxidative
      hydrolysis and water vapour distillation. This technology has no analogs both in
      this country and abroad. Unlike ordinary balneological medicines, those obtained
      by the new method do not contain inorganic matrix, show higher activity, and
      remain stable for a longer period. The primary composition of BACs isolated by
      the above technology was studied using solid-phase extraction and chromatomass
      spectrometry. Analysis of Extramine, a medicinal preparation from Novonukutskaya
      hydrogen sulfide mineral water (Siberian Matsesta), allowed to identify active
      components responsible for its therapeutic effects and elucidate mechanisms of
      their action. The 15-year-long experience with practical application of BACs
      obtained with the help of the new technology has demonstrated that they possesses
      antiallergic, antiviral, and analeptic activities. These compounds increase
      general resistance of the organism to infection, promote removal of toxic
      substances, accelerate wound and injury healing, and prevent the development of
      herpes infection.

PMID- 21086599
TI  - [Diagnosis and treatment of patients with primary "empty" sella turcica syndrome
      at the stage of sanatorium-and-spa rehabilitation].
AB  - The authors report the first attempt to develop the treatment strategy for
      patients with primary "empty" sella turcica syndrome based at a health resort
      facility. It is shown that combined therapy including radon baths and acupuncture
      at specific auricular points makes it possible to improve functioning of the
      pituitary-ovarian system, decrease body weight, normalize blood prolactin level,
      eliminate visceral obesity, enhance tissue sensitivity to insulin, reduce
      hyperinsulimenia and fertility problems (anovulation, hyperandrogenism, and
      hypoluteinism) associated with insulin resistance.

PMID- 21086600
TI  - [Modern methods of balneotherapy of digestive pathology at the Caucasian Mineral
      Waters spa-and-resort complex].
AB  - Scientists of Pyatigorsky State Research Institute of Balneotherapeutics are
      actively engaged in developing new medical technologies for rehabilitative
      treatment of patients with a variety of pathological conditions based on the
      current knowledge about mechanisms of action of natural therapeutic factors. Most
      of these original methods are included in the State Inventory of novel medical
      technologies by the Federal Supervisory Health and Social Development Service.
      The proposed medical technologies based on the application of natural and man
      made physical factors improved general effect of balneotherapy by 15-20% and
      accelerated recovery from the disease. Specifically, the length of post-treatment
      remission increased to 7-12 months and duration of temporary disability decreased
      2.5-3 times. Sick list payouts and economic expenditures of the state and the
      patients for medicinal preparations were reduced 3-4-fold while the quality of
      life and clinical prognosis significantly improved.

PMID- 21086601
TI  - [Myographic biofeedback training in combination with post-isometric relaxation of
      spastic muscles in patients with infantile cerebral paralysis].
AB  - Neurodynamic mechanisms underlying regulation of muscular tone are considered in
      the context of the integral systemic approach to the analysis of efficiency of
      adaptive preparation of spastic muscles to kinesitherapeutic procedures
      exemplified by myographic biological feedback (BFB) training of the affected
      muscles in children suffering cerebral paralysis. It is shown that the
      application of the post-isometric relaxation method immediately before
      biofeedback training seances increases effectiveness of these procedures and
      combined therapy of locomotor disorders at large.

PMID- 21086602
TI  - [Health improvement in children with ecological dysadaptation syndrome treated at
      a health resort].
AB  - A method for the spa-and-resort treatment of children residing under conditions
      of ecological discomfort has been developed. It includes drinking weakly
      mineralized hydrocarbonate-sodium sulfate-sodium-calcium carbon dioxide water
      from the Slavyanovsk spring and slightly carbonaceous mineral baths in
      combination with magnetotherapy. This treatment is shown to improve
      characteristics of somatic and neurological status, activate metabolic processes,
      accelerate lymphokinesis and blood circulation. Collectively, these effects
      enhanced the children's health potential.

PMID- 21086603
TI  - [Balneotherapy to the treatment of patients with hysteromyoma].
AB  - Patients with hysteromyoma are treated by radon therapy and balneotherapy with
      the use of iodine-bromine water. Radon therapy is known to produce a more
      pronounced effect than drinking of iodine-bromine water. At the same time, the
      latter treatment activates hyperemic processes in the skin and mucous membranes
      and thereby decreases density of myometrial nodular lesions and compact foci. It
      is concluded that radon therapy and the use of iodine-bromine water are the
      methods of choice for balneotherapy of patients with hysteromyoma.

PMID- 21086604
TI  - [On the development of a system of medical weather forecast for the Caucasian
      Mineral Waters spa-and-resort complex].
AB  - A system of medical weather forecast for the Caucasian Mineral Waters spa-and
      resort complex has been modified and updated based on the results of long-term
      observations of weather conditions in the region of interest with special
      reference to the bioclimatic regime, atmospheric circulation, aerosol pollution
      of the near-ground air, ultraviolet radiation, heliomagnetic activity, and
      meteopathic effects. This system provides a basis for the timely emergency
      meteopreventive treatment of meteodependent patients and therefore can be
      instrumental in enhancing efficiency of spa-and-resort rehabilitative therapy.

PMID- 21086605
TI  - [Effect of algal preparations on immunological and biochemical characteristics of
      rats with adjuvant arthritis].
AB  - Investigations with the use of a rat model of adjuvant arthritis have
      demonstrated long-term immune, biochemical, and anti-inflammatory effects of
      preparations based on green and brown marine algae from the Anapa region (the
      Black Sea). Comparative studies showed that the algal preparations are in many
      cases as efficient in terms of various biological actions as local therapeutic
      muds.

PMID- 21086606
TI  - [Predictive significance of initial morpho-functional characteristics for the
      evaluation of effectiveness of remedial correction of arterial hypertension].
AB  - Analysis of effectiveness of spa-and-resort treatment of 154 patients with
      arterial hypertension and metabolic disturbances has demonstrated predictive
      value of variations of biological characteristics which suggests their important
      contribution to beneficial outcome of rehabilitative therapy. Results of the
      study made it possible to distinguish the most essential aspects of metabolism
      and its regulation related to the success of spa-and-resort treatment.

PMID- 21086607
TI  - [The rationale for the use of microwave resonance therapy in combined treatment
      of patients with community-acquired pneumonia].
AB  - Inclusion of microwave resonance therapy using waves of various frequency and
      alternating wavelength ranges in the combined treatment of patients with
      community-acquired pneumonia promoted normalization of their disturbed prooxidant
      antioxidant status, correction of physico-chemical properties and functional
      activity of membranes.

PMID- 21086608
TI  - [The clinical scale for the assessment of psychic status of patients with chronic
      somatic diseases].
AB  - Diagnostic potential of the clinical scale for the assessment of psychic status
      (CSPS) of patients with chronic somatic diseases (CSD) was evaluated based on the
      results of observations that involved a total of 1,294 patients. For comparison,
      their conditions were estimated using a concise multifactorial questionnaire
      (CMFQ) to assess personality characteristics, 16-factor Kettell personality test,
      Spielberger's anxiety scale, and Beck depression inventory. Results of the study
      show that CSPS meets all requirements to psychometric tests as producing reliable
      and valid data. Specifically, it is characterized by high discriminative capacity
      and may be used to reveal a leading psychopathological syndrome and determine its
      severity for the choice of differential therapeutic strategies, assessment of
      dynamics of the psychic status in the course of therapy, estimation of its
      efficiency, and development of prognosis of the disease.

PMID- 21086610
TI  - [Psycho-physiological criteria for overtraining in athletes].
AB  - The objective of this work was to study major early signs of overstrain in
      athletes based on dynamic patterns of the most sensitive psycho-physiological
      symptoms during physical exercises and the post-training recovery period. The
      study included sport game players examined in the contest season. It was shown
      that reduction of simple visiomotor reaction time soon after cessation of
      training compared with that at rest may be indicative of adequate response of the
      central nervous system to physical exercise that activates central regulatory
      mechanisms under physiological conditions. It is concluded that these
      observations may be of use for the choice of exercise intensity on an individual
      basis and timely correction of training plans.

PMID- 21086609
TI  - [Problems of pelvic girdle asymmetry in patients with spinal osteochondrosis and
      remedial gymnastics].
AB  - This paper deals with the problems of pelvic girdle asymmetry in patients with
      spinal osteochondrosis. Effectiveness of medicamentous and rehabilitative
      treatment of such patients is compromised by destructive changes in the
      vertebrae. Analysis of locomotor disturbances and their dynamics under effect of
      remedial gymnastics prescribed on an individual basis showed that the main factor
      limiting success of osteochondrosis therapy is muscular disbalance in the pelvic
      girdle. This dictates the necessity to start prevention or treatment of the
      disease and rehabilitation of the patients from the correction of muscular
      asymmetry. The muscular corset should be formed so as to ensure dynamic
      equilibrium of muscular tone (between antagonist muscles) bearing in mind that
      disbalance in the tone of flexor and extensor muscles (both homo- and
      contralateral ones) contributes to recurring pain syndrome and further aggravates
      pelvic asymmetry. Its correction in due time constitutes a major condition for
      the prevention of diseases affecting not only joints of the lower extremities but
      also lumbar spine especially in patients subject to intense occupational and
      sports exertion.

PMID- 21086611
TI  - [Non-medicamentous methods for the treatment of chronic venous insufficiency:
      current state of the art].
AB  - Physical and balneotherapy along with medicamentous and compression therapy are
      basic components of conservative treatment of patients with chronic venous
      insufficiency of the lower extremities. Modern rehabilitative medical
      technologies help to prevent complications of this pathology, enhance clinical
      efficiency of the treatment, and improve the patients' quality of life provided
      they are applied with due regard for the stage of the disease and underlying
      pathogenetic factors.

PMID- 21086612
TI  - [Efficiency of medical and economic activities of a sanatorium-and-spa facility
      in the active phase of the public health system reform under macroeconomic
      instability].
AB  - Results of a comprehensive study have demonstrated that the reform of the public
      health system currently underway in this country provides conditions for the
      extension of medical care based at sanatorium-and-spa facilities with
      simultaneous rise in relevant expenses. Bearing in mind the unstable
      macroeconomic situation, this requires thorough monitoring medical and economic
      activities of health resorts for the purpose of enhancing cost efficiency. The
      goal of optimization can be achieved by increasing competitive capacity based on
      strict control of expenditures and income redistribution for financing the most
      promising projects.

PMID- 21086613
TI  - [The topical issues of the terminology, classification, and statistics of acute
      forms of ischemic heart disease].
AB  - The paper discusses the problems in the formation of statistical information on
      acute forms of coronary heart disease (IHD) in Russia and possible ways of their
      solution. Among other problems, there is the detection and notification of cases
      of sudden coronary death as an independent nosological entity that belongs to the
      acute forms of IHD. The terminology and classification of the acute forms of IHD,
      which affect the formation of statistical data, are considered. The consequences
      of underestimates of the role of a postmortem study, as the most important
      postmortem diagnostic method, in modern practical health care are discussed. The
      paper is largely debatable and intended for a wide circle of readers in order to
      attract their attention to the detection and notification of the acute forms of
      IHD in clinical practice, especially in cases of death from acute IHD in the
      prehospital stage.

PMID- 21086614
TI  - [Risk factors for myocardial infarction recurrence in young and middle-aged
      males].
AB  - AIM: To assess a set of risk factors (RF) for coronary heart disease in
      myocardial reinfarction patients aged less than 60 years. SUBJECTS AND METHODS: A
      multitude of probable RFs that might predispose to the development of MI or
      provoke its occurrence were studied in 526 male patients aged less than 60 years,
      who had primary (n = 281) and repeated (n = 245) myocardial infarction (MI) from
      the results of hospital treatment. RESULTS: Lipid metabolic disturbances,
      smoking, arterial hypertension (AH), foci of chronic infection, and overweight
      were ascertained to be the most common RFs in patients less than 60 years. There
      was a history of dyslipidemia (100%), AH, heart failure, and cardiac arrhythmias
      in the complicated course of repeated MI. When these RFs are combined, the
      likelihood of disease complications and death increases. CONCLUSION: According to
      the results of estimation of the spread of RFs for myocardial reinfarction, it is
      proposed to enhance the monitoring of lipidogram readings, blood pressure value,
      magnitude of the symptoms of heart failure, and serum glucose levels, and
      infection foci sanitization and to improve patients' awareness about a risk from
      smoking and lower physical activity.

PMID- 21086615
TI  - [Association of the serum level of apolipoprotein E with coronary artery disease
      and carotid artery atherosclerosis in Kyrgyz men with dyslipidemia].
AB  - AIM: To study an association of the serum level of apolipoprotein E (apo-E) with
      risk factors for coronary heart disease (CHD), blood lipids and that with CHD and
      carotid artery (CA) atherosclerotic lesion in Kyrgyz men with dyslipidemia.
      SUBJECTS AND METHODS: One hundred and three Kyrgyz men, including 48 with CHD and
      55 without this disease, were examined. A clinical examination was performed and
      blood lipid composition and serum glucose and apo-E levels were determined. The
      diagnosis of CHD was established in accordance with the conventional criteria.
      Whether atherosclerosis was present was determined by ultrasound duplex scanning.
      RESULTS: Low serum apo-E concentrations were associated with the presence of
      obesity, the higher blood levels of glucose and triglycerides. There was no
      correlation with other lipid metabolic parameters and the presence of CHD. A
      nonlinear relationship was noted between serum apo-E levels and CA
      atherosclerotic lesion, which was more frequently observed in patients with the
      apo-E level in the lower and upper quartiles. CONCLUSION: Low serum apo-E content
      is a poor factor and associated with obesity, hypertriglyceridemia, elevated
      serum glucose levels, and the development of CA atherosclerosis.

PMID- 21086617
TI  - [Influence of genetic factors on the development of target organ lesions in
      relation to age in diagnosis of arterial hypertension].
AB  - AIM: To analyze the impact of polymorphism of a group of genes encoding for
      endothelial function on the development of target organ lesions in arterial
      hypertension (AH) in relation to age. SUBJECTS AND METHODS: Six hundred and
      seventy-two AH patients (mean age 50.6 years; men 67%) were examined.
      Microalbuminuria (MAU) was estimated. Electrocardiography, echocardiography, and
      carotid ultrasonography were performed. A control group comprised 184 subjects.
      Single-nucleotide substitutions genotyping of the Glu298Asp endothelial NO
      synthase (eNOS), p22phox of NADPH oxidase subunit C242T, and angiotensin II type
      1 receptor (ATR1) A1166C gene polymorphisms was conducted by a polymerase chain
      reaction (PCR) via restriction fragment length polymorphism analysis, and M235T
      substitution genotyping of the G-6A polymorphism of the angiotensinogen gene was
      performed by a real-time allele-specific PCR. The impact of the polymorphisms on
      the development of MAU, left ventricular hypertrophy (LVH), carotid lesion was
      analyzed in the groups: AH was diagnosed in subjects aged less than 35 years (n =
      128) or older. The ultrasound signs of carotid lesion, LVH, and MAU were revealed
      in 65, 39, and 10.5% of the patients with AH, respectively. RESULTS: The
      subgroups showed differences in the distribution of polymorphisms of the study
      genes in relation to age at AH detection. CONCLUSION: In patients with AH
      diagnosed at less than 35 years of age, pathological changes in the carotid are
      associated with a G allele of the Glu298Asp eNOS polymorphism (odds ratio (OR) =
      2.3; p = 0.016) and with an T allele of the p22phox of NADPH oxidase subunit
      C242T polymorphism (OR 1.7; p = 0.049). In this age subgroup, LVH was associated
      with an A allele of the Glu298Asp eNOS polymorphism (OR = 1.9; p = 0.037), MAU
      was with an A allele of the Glu298Asp eNOS polymorphism (OR = 3.6; p = 0.02) and
      a C allele of the ATR1 A1166C gene polymorphism (OR = 2.6; p = 0.034).

PMID- 21086616
TI  - [Trends in subclinical atherosclerosis in patients with arterial hypertension
      associated with diabetes mellitus: a relationship between blood pressure achieved
      with antihypertensive therapy and body weight].
AB  - AIM: To analyze carotid artery morphofunctional changes in patients with arterial
      hypertension (AH) associated with type 2 diabetes mellitus (CD2) on regular
      antihypertensive and sugar-lowering therapy in relation with the changes in the
      diurnal blood pressure (BP) profile, the quality of metabolic control, and
      baseline clinical and laboratory data. MATERIALS AND METHODS: Seven-six patients
      with CD2-associated AH who had received regular antihypertensive and sugar
      lowering treatment without statins for 12 months were examined. The intima-media
      thickness (IMT) in the common carotid artery (CCA) was estimated by ultrasound
      scanning; the compliance and stiffness indices were calculated. The values of 24
      hour BP monitoring, glycemic control, and blood lipids were studied. RESULTS:
      Among the patients with increased CCA IMT (Group 1), women were three times more
      than among those without it (Group 2). Subclinical atherosclerosis progression as
      an annual average CCA IMT increment of 0.08 mm was detected in the absence of a
      less than 7-mm Hg decrease in 24-hour mean systolic BP and/or a 24-hour mean BP
      of less than 134/80 mm Hg or if, during adequate BP control, HbA1 exceeded 9%.
      Group 1 women showed increased body mass index and a trend for worse vascular
      elastic properties. Group 2 displayed not only a CCA IMT reduction (from 0.94 +/-
      0.03 to 0.83 +/- 0.03 mm; p < 0.01), but also a CCA decrease that seemed to show
      reduced vessel wall thickness. There were no changes in the CCA lumen in Group 1.
      Comparable control of glycemia and blood lipid-transport system indices was
      achieved in both groups. The magnitude for 24-hour BP reduction in which there
      was no subclinical atherosclerosis under stable glycemic control was determined.
      CONCLUSION: The results of the study suggest a correlation between a inadequate
      BP reduction, worse elastic properties of large-sized arteries, and higher body
      mass index in patients (mainly women) with CD2 and underline the importance of
      correcting body weight and achieving goal BP in this group of patients.

PMID- 21086618
TI  - [Psychological status of hypertensive patients consuming higher amounts of table
      salt].
AB  - AIM: To estimate a possible relationship of neurotic personality disorders to
      increased dietary salt intake. SUBJECTS AND METHODS: Two hundred and thirty
      patients with essential hypertension were examined. Salt taste sensitivity
      threshold and daily urinary sodium excretion were determined; the psychological
      status of the patients was rated by the Mini-Mental State Examination
      questionnaire; their attitude towards to disease was assessed by the Bekhterev
      Institute personality questionnaire, the severity of depression was evaluated by
      the Beck depression inventory. RESULTS: The hypertensive patients consuming
      excessive amounts of salt have been ascertained to complain of cardiovascular and
      neurotic disorders more frequently; their disease is accompanied by frequently
      evolving hypertensive crises. Anxiety and tension are prevalent in their
      psychological status. Almost 50% of the patients have depression. A harmonious
      disease attitude is seen in only a third of cases whereas the neurasthenic and
      anxious types play a dominant role. CONCLUSION: The patients taking higher salt
      amounts are observed to seek medical advice on the one hand and to show a
      predominance of neurasthenic and anxious disease attitudes with a tendency
      towards incompliance on the other. The findings show it necessary to notify
      hypertensive patients during their examination and management.

PMID- 21086619
TI  - [Determinants of the respiratory system status in hypertensive disease].
AB  - AIM: To analyze the respiratory system in hypertensive disease (HD). SUBJECTS AND
      METHODS: Forty-six hypertensive patients (mean age 43.2 +/- 4.0 years) were
      examined. Office blood pressure (BP) was measured. Electrocardiography,
      echocardiography, color Doppler ultrasonography of the brachial artery, 24-hour
      BP monitoring, spirography, body plethysmography, and study of the diffusion lung
      capacity for carbon monoxide were performed. The serum levels of interleukins 6,
      8, and 10, tumor necrosis factor (TNF), and C-reactive protein (CRP) were
      measured. RESULTS: Inflammatory processes have been ascertained to contribute to
      the development and progression of HD. The increase in HD degree and stage is
      attended by a significant elevation of the plasma concentrations of
      proinflammatory cytokines, TNF, and CRP, which is due to the contribution of
      inflammatory processes in the vessel wall to the development of endothelial
      dysfunction, vascular remodeling, and organ lesions, including diminished lung
      function in HD. CONCLUSION: Arterial hypertension, inflammatory indicators,
      endothelial function, and the degree of lesions to organs, including those in the
      respiratory system, are related. The basis for this relation is the common
      neurohumoral mechanisms of progression of nonspecific inflammation, endothelial
      dysfunction, and target organ lesions.

PMID- 21086620
TI  - [The specific features of left cardiac cavity remodeling in patients with chronic
      obstructive pulmonary disease and chronic cor pulmonale].
AB  - AIM: To study left ventricular structural and functional changes in patients with
      chronic obstructive pulmonary disease (COPD) and chronic cor pulmonale (CCP) at
      different stages of a cardiac remodeling process. SUBJECTS AND METHODS:
      Echocardiography was used to examine 98 patients with COPD complicated by the
      development of CCP in a number of cases. The significant signs of CCP were absent
      in 19 patients; the signs of compensated and decompensated CCP in 41 and 38
      patients, respectively. RESULTS: In the patients with COPD, the formation of CCP
      during remodeling of the heart involves its left cavities whose changes lie in
      the occurrence of left ventricular (LV) diastolic dysfunction, mainly of the
      restrictive type, in ventricular spherization, higher myocardial systolic
      tension, in tendencies towards increases in LV mass index, left atrial sizes, and
      in the indices reflecting LV systolic dysfunction. The LV diastolic dysfunction
      correlates with the degree of right ventricular hypertrophy and dilatation and
      the presence of complete right bundle-branch block. CONCLUSION: Progressive
      worsening of diagnostic filling of the left ventricle and its systolic function
      is an additional factor aggravating hemodynamic disorders in patients with COPD
      and CCP, which should be kept in mind on choosing an appropriate therapy for
      patients with CCP.

PMID- 21086621
TI  - [Thromboxane-prostacyclin balance and platelet aggregability in patients with
      minor cardiac abnormalities].
AB  - AIM: To reveal changes in the thromboxane-prostacyclin balance and platelet
      aggregability in patients with various variants of minor cardiac abnormalities.
      SUBJECTS AND METHODS: Six-five patients (mean age 23.0 +/- 0.7 years) with minor
      cardiac abnormalities and 10 apparently healthy individuals were examined.
      Platelet aggregation induced by adrenaline, adenosine diphosphate, collagen) and
      the plasma levels of thromboxane B2 (TxB) and 6-keto-prostaglandin F1alpha (6
      keto-PGF1alpha) were determined. RESULTS: Patients with abnormally located
      chordae (ALC) were found to have no deviations in the thromboxane-prostacyclin
      balance and platelet aggregability. Only decreased collagen aggregation was
      recorded in the groups of first-degree mitral prolapse (MP) and first-degree MP +
      ALC; in second-degree MP and second-degree MP + ALC, there was a reduction in
      platelet aggregation on all inductors and an increase in TxB2. Patients with
      myxomatous degeneration of the mitral valve exhibited reduced collagen-induced
      platelet aggregation and lower plasma 6-keto-PGF1alpha levels. CONCLUSION: The
      most pronounced changes in the thromboxane-prostacyclin balance and platelet
      aggregability were found in patients with MP and second-degree regurgitation,
      three intracardiac micro-abnormalities, and myxomatous degeneration of the mitral
      valve.

PMID- 21086622
TI  - [Renin inhibitors--new direction in the treatment of arterial hypertension].
AB  - The paper covers current problems in the treatment of arterial hypertension.
      Renin is an important and promising therapeutic target. The direct renin
      inhibitor aliskiren (Rasilez) is a promising current effective antihypertensive
      agent that has cardio- and nephroprotective effects. The paper considers a number
      of clinical studies that have proven the antihypertensive effect of aliskiren and
      revealed its benefits versus other drugs recommended for blood pressure lowering.
      It is assumed that this agent may be used in combinations with angiotensin
      converting enzyme inhibitors, thiazide or thiazide-like diuretics, and calcium
      antagonists. Moreover, aliskiren neutralizes the effect of feedback in the
      compensatory increase in the activity of plasma renin.

PMID- 21086623
TI  - [Aortic aneurysm: diagnosis and treatment].
AB  - The paper deals with the topical issues of diagnosis of aortic aneurysms and with
      the current possibilities of treating this pathology. It presents epidemiological
      data, assessment of the risk of aortic rupture, a patient management regimen
      according to screening results, and information on the new miniinvasive aortic
      aneurysm treatment--endovascular replacement using self-expandable stent-grafts.

PMID- 21086624
TI  - [The clinical value of determination of natriuretic peptides in acute coronary
      syndrome].
AB  - The production and release of natriuretic peptides (NPs) into the bloodstream are
      stimulated by increased left ventricular wall tension during volume overload. In
      ischemia, NPs are secreted by myocardial cells in response to stress or overload,
      particularly in the development of myocardial systolic dysfunction. The review
      details the time course of changes in amino acid N-terminal proBNP in acute
      coronary syndrome (ACS) with and without ST-segment elevation and discusses the
      role of the index in defining the tactics of treatment and prognosis in patients
      with ACS.

PMID- 21086625
TI  - [The diagnostic value and clinical significance of a method for estimating the
      arterial stiffness by cardio-ankle vascular index].
AB  - The review presents the data of clinical studies of a new method for estimating
      the arterial stiffness by cardio-ankle vascular index (CAVI). The most
      significant factors influencing the vascular wall are analyzed and a CAVI
      measuring procedure and a calculation algorithm are described in detail. An
      association of the estimation of CAVI with other procedures determining the
      rigidity of the arterial wall is analyzed. A possibility for the practical
      application of this index to the study of the elastic properties of the vascular
      wall and for its use as a surrogate criterion to evaluate the vasoprotective
      effect of antihypertensive agents is considered.

PMID- 21086626
TI  - [Broken heart syndrome or Takotsubo cardiomyopathy. (Literature review and
      clinical observations)].
AB  - Takotsubo cardiomyopathy is an acute cardiac syndrome that mimics ST segment
      elevation myocardial infarction. It is characterized by transient local
      contractility disturbances as akinesis of the apical and middle segments of the
      left ventricle concurrent with hyperkinesis of its basal portions in the absence
      of significant coronary artery changes. A description of 2 clinical cases and a
      review of literature on this rare myocardial disease are given.

PMID- 21086627
TI  - [Interaction of the neurohumoral and immune mechanisms of progression of
      myocardial damage].
AB  - The review summarizes data on the interference of the neuroendocrine and immune
      mechanisms of myocardial remodeling. It shows a role of the effectors of the
      renin-angiotensin-aldosterone (aldosterone and angiotensin II) and
      sympathoadrenal (noradrenaline) systems in the activation of macrophages, the
      production of proinflammatory cytokines and inflammatory cell chemoattractants.
      It is noted that proinflammatory cytokines in turn promote the activation of
      these neuroendocrine systems. Natriuretic peptides exert an anti-inflammatory
      effect, but their production can be activated by proinflammatory cytokines.

PMID- 21086628
TI  - [Expression of matrix metalloproteinases 2 and 9 and their tissue inhibitors 1
      and 2 in papillary thyroid cancer: an association with the clinical,
      morphological and ultrastructural characteristics of a tumor].
AB  - Papillary thyroid cancer (PTC) was ascertained to be characterized by a
      significant expression of matrix metalloproteinases (MMP-2 and 9) and a TIMP-2
      inhibitor and decreased TIMP-1 accumulation in the cytoplasm of tumor cells; at
      the same time a combination of high cytoplasmic MMP-9 expression with no TIMP-1,
      as well as triple positive co-expression of MMP-2, MMP-9, and TIMP-2 are poor
      immunohistochemical indicators. The results of the performed study suggest that
      the detection of the types of expression of MMP-9+/TIMP-1 and MMP-2+/MMP-9+/TIMP
      2+ is associated with the possible progression of a tumor process and concurrent
      with poor clinical and morphological signs, such as the large size of the tumor,
      the presence of intravascular invasion and regional metastases, organ capsular
      invasion, and low ultrastructural tumor cell differentiation. Thus, changes in
      the tumor expression of the extracellular matrix enzymes MMR-2 and MMP-9 and
      their inhibitors TIMP-1 and TIMP-2 along with the major clinical, morphological,
      and ultrastructural signs of the disease are important additional indicators for
      analyzing the malignant potential of PTC.

PMID- 21086629
TI  - [The morphological and immunohiochemical features of foci of adenomyosis: in its
      concurrence with endometrial adenocarcinoma].
AB  - The purpose of the investigation was to study the morphological variants and
      molecular changes of the endothelial component of adenomyosis (AM) concurrent
      with endometrial adenocarcinoma (EAC). Monoclonal and polyclonal antibodies to
      ApoCas, Cl 2, 3, and 5, Ki-7, MMP-2, MMP-9, TIMP-1, E-cadherin, COX-2, EGFR, and
      VEGF were used as primary antibodies. The AM foci displayed the following types
      of epithelial changes: the epithelium corresponding to the proliferation stage;
      epithelial hyperplasia with and without atypia; atrophic epithelium. There was an
      increased expression of ApoCas, Ki-67, MMP-2, MMP-9, COX-2, VEGF, and EGFR, which
      increased from proliferation to hyperplasia with atypia. The maximum expression
      of the markers was seen in EAC. The foci of AM, which corresponded to epithelial
      hyperplasia with atypia, were characterized by the oncomarker changes supporting
      its malignant potential: elevated Ki-67 and EGRF, reduced E-cadherin, changes in
      MMP-2, MMP-9, TIMP-1, and claudins-2, -3, and -5.

PMID- 21086630
TI  - [Precancerous changes in the epithelium of the cervix uteri: terminology and
      principles of differential diagnosis].
AB  - Three most popular classifications of precancerous changes in the epithelium of
      the cervix uteri, their merits and demerits, morphological criteria, and
      principles of differential diagnosis are considered. The advantage of the SIL
      classification is the more accurate reflection of the biology of the process and
      a common terminological base proposed for histological and cytological
      classifications, which is particularly important to overcome difficulties in
      clinical interpretation. LGSIL provides a high rate of diagnostic errors;
      therefore elaboration of unique criteria for histological evaluation is a problem
      of great importance. HGSIL should be differentiated with regenerative and
      atrophic processes in the cervix uteri with a special accuracy.

PMID- 21086631
TI  - [Argyrophilic nucleolar organizer region associated proteins in adenomas with
      varying colonic dysplasia and adenocarcinoma].
AB  - Argyrophilic nucleolar organizer region associated (Ag-NOR) proteins were studied
      in rectosigmoid epithelial tumors for diagnostic purposes. Silver nitrate
      staining was carried out in accordance with the standardized protocol. The
      quantity, area, area index of Ag-NOR proteins were automatically determined by
      computer image analysis. There were statistically significant differences in the
      quantity, area, area index of Ag-NOR proteins between the groups: the mucosa
      (lower 2/3 crypts), mild, moderate, and severe dysplasia of adenoma. Only the
      estimation of the area index of Ag-NOR proteins indicated statistically
      significant differences between severe dysplasia and highly differentiated
      adenocarcinoma. Colonic adenomas showed a correlation of the activity of Ag-NOR
      proteins with epithelial dysplasia, but no correlation with the size and
      histological type of their structure.

PMID- 21086632
TI  - [Intraoperative telediagnosis of breast biopsies].
AB  - Intraoperative real-time telediagnosis from cryostat sections of the breast can
      increase the quality of postmortem diagnosis. Moreover, the average accuracy of
      histological diagnosis was as high as 93.5% or increased by 4.4% as compared with
      traditional microscopy. According to the nature of the pathological process, this
      increase reached 86.7% (by 5.4%) for nontumor pathology and 95.9 (by 5.1%) and
      95.8% (by 1.9%) for benign and malignant neoplasms, respectively. Intraoperative
      telediagnosis was most effective in a rare breast pathology that presented
      difficulties in the use of traditional microscopy, by calling for discussion of
      the histological pattern and colleagues' consultative support.

PMID- 21086634
TI  - [Molecular genetic study of benign pigmented neoplasms by fluorescence in situ
      hybridization].
AB  - Twenty samples of benign pigmented neoplasms of the skin, including 9 intradermal
      nevi and 11 complex ones, were investigated. Fluorescence in situ hybridization
      was used to detect the copy number of the RREB1 (6p25), MYB (6q23), and CCND1
      (11q13) genes. Analysis of the findings revealed no significant changes
      characteristic of melanoma in the nevi. However, the authors established that
      there was a direct correlation between the copy number of the MYB and RREB1 genes
      and that the amount of the MYB gene most frequently deviated from the normal
      values. In addition, a relationship was found between the number of MYB gene
      copies and the depth of the epidermal layer. In cases of an intradermal nevus,
      the copy numbers of the CCND1 and MYB genes were shown to vary more greatly than
      in cases of a complex nevus.

PMID- 21086633
TI  - [Are human papillomaviruses responsible for the occurrence of bladder cancer].
AB  - A female patient with recurrent bladder cancer underwent complex examination. The
      primary tumor removed in 2004 showed human papillomavirus (HPV) 16 DNA, mRNA
      corresponding to HPV16 oncogene E7, as well as HPV16 protein E7. The patient is a
      smoker who has been working at a chemical factory for over 20 years. During tumor
      recurrence in 2009, there was no DNA of high-risk HPV types in the cancer cells.
      HPV16 E7protein and cellular p 16(INK4alpha), an indicator of HPV-induced
      carcinogenesis, were not found. Colposcopy revealed no precancerous changes in
      the epithelium of the cervix uteri. The cervical epitheliocytes contained no high
      risk HPV DNA, E7 and p16(INK4alpha) proteins. It seems expedient to continue in
      vitro studies of the possible role of HPV in urothelial carcinogenesis on an
      experimental model.

PMID- 21086635
TI  - [The mechanism of lung tissue remodeling in the progression of idiopathic
      pulmonary fibrosis].
AB  - The aim of the investigation was to study the specific features of morphological
      manifestations and the molecular bases of lung tissue remodeling in progressive
      idiopathic pulmonary fibrosis (IPF). The investigation used open and
      transbronchial biopsy specimens from 110 patients with IPE/idiopathic pneumonia
      syndrome in 1997 to 2008. Immunohistochemical analysis was carried out on serial
      paraffin-embedded lung tissue slices from 20 patients with IPF and 20 control
      patients. Immunohistochemical staining for the detection of antigens in the
      paraffin-embedded slices was made using the antibodies to MMP-1, MMP-2, MMP-7,
      TIMP-4, Apo-CAS, PCNA, PDGF, EGFR, CD34, and SMA. Nonparametric statistical
      methods were employed. Our findings have indicated that in early-stage IPF, there
      are proliferating myofibroblasts in the myofibroblastic foci, mainly in the
      bronchioloalveolar transitional zone (BATZ), which express PCNA and PDGF. Both in
      early- and late-stage IPF, there were signs of increased readiness of the
      alveolar and bronchiolar epithelium of BATZ for apoptosis, as judged from Apo-CAS
      expression. At the same time no Apo-CAS expression was recorded in the
      myofibroblasts. In the early stage of the disease, the expression of MMP-1, MMP
      2, MMP-7, and TIMP-4 in the epitheliocytes, macrophages, fibroblasts, and
      myofibroblasts was higher than that in the late stage of IPF. At the same time,
      late-stage IPF was characterized by the higher expression in all lung tissue
      cells than was early-stage IPF. There was also a significant increase in vessel
      density in both early and late stages of IPF as compared with intact lung tissue
      particularly in the BATZ in the control group. Thus, lung tissue remodeling in
      the progression of IPF from the early to late stage of the disease comprises
      interrelated processes that are largely localized in the BATZ, such as immune
      inflammation with pathological reparation, neoangiogenesis, apoptosis, and
      proliferation of epitheliocytes and myofibroblasts, which lead to the development
      of interstitial fibrosis and adenomatosis of the lung.

PMID- 21086636
TI  - [Acute gastroduodenal erosions and ulcers in coronary heart disease,
      cerebrovascular disease, and chronic obstructive pulmonary disease].
AB  - A total of 4684 autopsies made at Moscow multidisciplinary hospitals in 2002-2008
      were studied to reveal the incidence and morphological features of acute
      gastroduodenal erosions and ulcers in coronary heart disease (CHD),
      cerebrovascular disease (CVD), and chronic obstructive pulmonary disease (COPD).
      Cases with combined, background, and concomitant diseases that could be
      independent causes of gastroduodenal lesions were excluded. Patients older than
      60 years with infarctions of the myocardium or brain, a concurrence of CHD, CVD,
      and COPD, and various diseases with chronic heart failure syndrome, particularly
      in the presence of arterial hypertension and diabetes mellitus should be referred
      to as a risk group for acute gastroduodenal erosions and ulcers and their induced
      hemorrhages.

PMID- 21086637
TI  - [Prognostic value of morphological signs of the activity of tuberculous
      inflammation in patients with circumscribed drug-resistant pulmonary
      tuberculosis].
AB  - The paper provides the morphological characteristics of a specific process in
      patients with drug-resistant pulmonary tuberculosis. Morphological study of
      intraoperative samples has shown a predominance of common active inflammatory
      changes in most cases. There is evidence for an association of the morphological
      activity of a tuberculous process with the clinical types and duration of the
      disease and their spectrum of drug resistance. The high morphological activity of
      specific inflammation (IV-V) substantially increases the risk of specific
      postoperative complications and relapses in the late follow-up periods.

PMID- 21086638
TI  - [Retinal lesion in experimental chlamydia eye infection].
AB  - Until the present time, ophthalmic chlamydiasis has been generally associated
      with diseases of auxiliary organs of the eye and its anterior segment:
      conjunctivitis and iridocyclitis. The morphological substrate of eye posterior
      segment lesion caused by C. trachomatis and C. pneumonia was studied in this
      investigation. The pathomorphological pattern characteristic of chlamydia-induced
      rabbit retinal and vitreous body lesions is composed of vitreoretinal lymphocyte
      macrophageal infiltrations of varying intensity, posterior hyaloid membrane
      detachment, peripheral foci or folding of the retina, impaired nuclei of
      photoreceptors and bipolar neurons, pigment epithelial damage occurring in
      different concurrences in relation to the species of a causative agent and the
      clinical picture.

PMID- 21086639
TI  - [Morphofunctional characteristics of the fetoplacental complex in pregnant women
      with an exacerbation of herpes virus infection and pathomorphological changes in
      fetal organs].
AB  - Impaired placental cholesterol synthesis in a pregnant woman with an exacerbation
      of herpesvirus infection is characterized by disturbances in placental hormone
      biosynthesis, causing severe morphological changes in fetal organs (liver,
      adrenals, lungs, and thymus).

PMID- 21086640
TI  - [Prognistic value of a study of the expression of argyrophilic nucleolar
      organizer region associated proteins in case of papillary thyroid cancer].
AB  - The prognosis in papillary thyroid cancer (PTC) is usually good. Ten-year
      survival can be seen in 90-98% of patients. Immunohistochemical study (antigen K
      67) ascertained that a female patient with PTC had a low number of proliferating
      cells, which is usually seen in the favorable course of the disease. However, in
      the presented case, PTC was highly aggressive and showed a significant invasive
      growth, provided regional and distant metastases, rapidly progressed and, despite
      the performed surgical treatment, the patient died due to disease progression 3
      months after surgery. This discrepancy between the number of proliferating cells
      and the aggressive course of PTC should be explained by the high expression of
      argyrophilic nucleolar organizer region associated proteins nucleofozmin and
      nucleolin, detected by immunohistochemical study, which is known to cause an
      increase in the rate of a mitotic cycle rate and to promote intercellular
      adhesion and enhancement of invasive growth and metastatic spread. Various
      factors involved in the regulation of proliferation of cells and their capacity
      for invasion and metastasis should be studied to make the most objective
      estimation of the degree of malignancy of a tumor and its prognosis.

PMID- 21086642
TI  - [Aneurysmal bone cyst in children].
AB  - Aneurysmal bone cyst (ABC), a tumor-like destructive lesion, is characterized by
      the presence of cavities of different sizes, which are filled with blood,
      connective tissue-septated with fibroblasts, histiocytes, osteoclast
      multinucleated giant cells, osteoids, bone trabecules, and accompanied by high
      intraosseous pressure. ABC most frequently occurs in the second decade of life.
      ABC is located in the metaphyseal area in children, by displacing to the
      diaphysis during their growth. Surgery is a basic treatment for ABC. Its relapses
      frequently occur, which depends on the method of a surgical intervention,
      methodic activity, and the belonging to a risk group (including a combination of
      age, cyst size, process phase, and location).

PMID- 21086641
TI  - [Multiple gliosarcoma metastases in the cauda equina roots].
AB  - The authors report a rare a case of gliosarcoma metastases in a 28-year-old male
      patient. The cauda equina roots were involved after brain tumor 16 months ago,
      which, on microscopic study, had a biphasic pattern and heterogeneous staining in
      the reaction with antibody to GFAP and vimentin; the tumor cells did not express
      EMA, EA, and desmin. Gliosarcoma was diagnosed, by taking into account
      morphological and immunohistochemical data. Tumor tissue of the cauda equine
      roots had the same immunophenotype as the brain tumor with a predominance of
      glial component, which permitted the source of metastases to be ascertained.

PMID- 21086643
TI  - [Current views of the molecular mechanisms of gastric cancer progression].
AB  - The available technologies have expanded our knowledge about the mechanisms of
      oncoprogression. Studies of the Wnt signaling pathway in the neoplastic cells
      could identify new promising markers in assessing the course and prognosis of
      this disease. beta-catenin as a key protein of the Wnt pathway is involved in the
      regulation of tumor proliferative activity and in the processes of epithelial
      mesenchymal transformation, by regulating E-cadherin metabolism and affecting the
      close contacts of the gastric epithelium. A competitive interaction between P
      cadherin and beta-catenin without forming reasonably close contacts is another
      cause of impaired intercellular interactions and tumor metastases. Claudin-1
      expression in the tumor pool as a marker of invasion requires further
      investigations. Traditional markers of proliferation and apoptosis, such as Ki
      67, p53, and bcl-2, may be further used to estimate the rate of tumor growth.

PMID- 21086644
TI  - [Effect of new polyprenol drug ropren on anxiety-depressive-like behavior in rats
      with experimental Alzheimer disease].
AB  - Influence of the chronic administration of ropren (Trademark)--a plant
      preparation based on the neutral fraction of extract of spruce and pine needles-
      on affective status in male rats with amyloid peptide (Abeta(25-35)) induced
      amnesia has been studied. Ropren was administered per os in a dose of 8.6 mg/kg
      for 28 days. Anxiety, depressive-like behavior, and behavioral reactions were
      assessed in the elevated plus maze, forced swimming, and open field tests. The
      four-week treatment revealed significant anxiolytic and antidepressant effects of
      the drug. Ropren administration improved various behavioral parameters. The
      obtained results show that ropren ameliorates behavioral deficits in animal model
      relevant to Alzheimer's disease and indicate that Ropren is potentially active in
      the management of affective impairments in the experimental model under
      consideration. It also has a profound beneficial effect on the anxiety and
      depressive-like behavior in rats with model Alzheimer's type dementia, and thus
      may prove to be a novel natural treatment.

PMID- 21086645
TI  - [Anxiolytic afobazole action self-evaluated by patients with anxiety-asthenic
      disorders].
AB  - Self-evaluation of single-dose (15 mg) action and course treatment (30 mg daily)
      results were studied in patients with anxiety and asthenic disorders treated with
      the new anxiolytic afobazole. Also, relationships between self-evaluated
      parameters and personal features, clinician-rated therapeutic changes, and
      treatment effectiveness were analyzed. The study was conducted according to
      formalized protocol using standard scales and methods. Results suggest that
      higher self-rated tolerability and patient acceptability were associated with
      afobazole treatment in comparison to benzodiazepines. The results revealed
      relationships between self-evaluated single-dose effects of afobazole and other
      parameters, personal features, cognitive impairments severity, main drug effects,
      and overall treatment effectiveness.

PMID- 21086646
TI  - [Effect of tropoxin on cerebrovascular effects of meta-chlorophenylpiperazine and
      serotonin].
AB  - Experiments on rats showed that meta-chlorophenylpiperazine, as well as
      serotonin, decreases cerebral blood flow registered in internal carotid artery of
      narcotized animals. Therefore, this agonist of postsynaptic 5HT(2B/2C) receptors
      can be used for directed search of new antimigraine drugs. Tropoxin (10 mg/kg)
      substantially reduces constrictor reactions of cerebral blood vessels induced by
      meta-chlorophenylpiperazine. The effect was observed during both prophylaxis and
      treatment of the model disorder with this drug.

PMID- 21086647
TI  - [Effect of magnesium sulfate on characteristics of cerebral hemodynamics under
      conditions of postischemic brain injury].
AB  - Effect of magnesium sulfate (50 and 100 mg/kg) as a corrector of postishemic
      brain injury has been experimentally studied. It is established that both
      therapeutic and preventive introduction of magnesium sulfate limits early
      postishemic hypoperfusion and hypotension.

PMID- 21086648
TI  - [Integrated assessment of endothelio- and cardioprotective activity of macrolide
      antibiotics in nitric oxide deficiency model].
AB  - Experiments on laboratory animals with nitric oxide deficiency modeled by the
      introduction of L-NAME (NO-synthase inhibitor) revealed the endothelio- and
      cardioprotective effects of clarithromycin, josamycin, roxithromycin, midecamycin
      and azythromycin. The administration of these macrolides leads to a decrease in
      the resulting area of the diagram of functional indices of the state of vessels
      and myocardium, which is approaching the corresponding area for intact animals.

PMID- 21086649
TI  - [Effect of hepatoprotector remaxol infusion on liver function in obstructive
      jaundice model in rats].
AB  - Remaxol is a new infusion hepatoprotector that contains succinic acid, inosine,
      methionine and methylglucamine. The hepatoprotective effect of remaxol on the
      liver function has been studied on the model of obstructive jaundice in rats, on
      the terms of one and two weeks after ligation of the common bile duct (M. A.
      Aller, et al., 2004). Sixty rats were randomly divided into six groups: sham
      operated rats with cholestasis, 0.9% NaCl treated rats with cholestasis, and
      remaxol treated rats with cholestasis, all on the one week (per os n=10) and two
      weeks (n=10) terms. Remaxol was injected into the tail vein in a dose of 1 ml/100
      g during the first week after the induction of cholestasis. The rats were removed
      from the experiment after one and two weeks of postoperative period,
      respectively. The size and weight of the liver and the degree of ascites were
      measured, and the blood samples were taken to analyze for bilirubin, alkaline
      phosphatase, gamma-glutamyl transpeptidase, alanineaminotransferase,
      aspartataminotransferase. Morphological changes in the liver were also studied.
      The biochemical parameters of blood and morphological evolution of tissue of
      liver in both one and two weeks after the induction of cholestasis showed a
      significant hepatoprotective effect of remaxol.

PMID- 21086650
TI  - [Correction of antioxidant system disorders in children with acute intestinal
      infection].
AB  - Administration of reamberin leads to rapid reduction of the intoxication
      symptoms, improves general condition, and reduces fever stage duration. The
      dynamics of inflammatory symptoms is characterized by decreasing duration of
      hemocolitis in comparison that in patients receiving glucose-salt solutions.
      Reamberin accelerates normalization of the chemiluminescence indices, reduces the
      intensity of oxidative processes (to within 3-5 days) in patients with high level
      of free-radical oxidation, and leads to decreasing endogenous intoxication on
      early terms of the disease. Removal of the dysbalance between oxidation and
      antioxidant systems, especially in cases of serious shigellosis and in patients
      with high level of lipid peroxidation, favors a decrease in the damaging action
      of free radicals and eliminates metabolic disturbances in children within early
      reconvalesce period.

PMID- 21086651
TI  - [Efficiency of emoxipine in treatment of multiple organ failure in newborns].
AB  - Prospective, placebo-controlled, simple "blind" randomized study of the effect of
      emoxipine (2-ethyl-6-methyl-3-oxypyridine hydrochloride) on the dynamics of
      central hemodynamics, content of lipid peroxidation products in tracheo-bronchial
      lavage, and severity of clinical sickness was performed in newborn children with
      multiple organ failures (MOF). The obtained results showed that a 10-day course
      of the intravenous administration of emoxipine in a single dose of 10 mg/kg
      improved the systolic function of myocardium of left ventricle, limited lipid
      peroxidation in broncho-pulmonary system, and increased oxygen delivery to
      tissues. These effects of emoxipine were accompanied by a clinically significant
      improvement of neurological status, reduction of the need for artificial
      ventilation of lungs, and decrease of mortality in newborns with MOF diagnosis.

PMID- 21086652
TI  - [Antiproliferative and antioxidant activity of new dihydroquercetin derivatives].
AB  - Effect of nine new derivatives of dihydroquercetin (taxifolin) on the viability
      of cultivated normal and tumor cells, their antioxidant activity, and
      interconnection of the antioxidant activity with the chemical structure have been
      studied. Among these dihydroquercetin derivatives, the maximum antiproliferative
      activity on the model of rat fibroblast culture exhibited KN-2, KN-4, KN-7, and
      KN-8 compounds, while KN-7 and KN-8 compounds also showed maximum activity on the
      model of MCF-7 tumor cell culture (human breast cancer). The maximum general
      antioxidant activity was observed for the native dihydroquercetin and KN-8
      compound. There is a strong correlation (with a correlation coefficient of 0.93)
      between the antiproliferative effects of dihydroquercetin derivatives on murine
      skin fibroblasts and MCF-7 cells (human breast cancer).

PMID- 21086653
TI  - [Humic substances: pharmacological properties, mechanisms of action, and
      prospects for use in medicine].
AB  - In recent years, the group of natural compounds called humic substances has drawn
      increasing interest of researchers both in, Russia and abroad. The properties of
      humic substances were studied and attempts of creating related medical
      preparations were undertaken. The article summarizes and reviews information
      about the pharmacological properties of humic substances and their possible
      mechanisms of action, analyzes relationships and separates the primary and
      secondary factors, and assesses prospects of using humic substances in medicine.

PMID- 21086654
TI  - [Construction and validation of a quantitative assessment of speech
      intelligibility for speech disorders].
AB  - Intelligibility of speech measure is based on the perception of the listeners.
      OBJECTIVE: The aim of this study was the construction and the validation of a
      quantitative test of speech disorders severity allowing the the follow up and the
      measure of management impact. MATERIAL AND METHOD: After a first step of
      construction and feasibility, the psychometric validation was performed. 37
      patients with a speech disorder and 13 normal subjects were recorded. The
      reference was the global score obtained by reading a text. The whole recordings
      were scored by a panel of 5 judges. The test was composed by a automatic series
      of words (the months of the year) with a phono-orthographic score, the semantic
      transcription of a list of words and sentences, a qualitative score of
      spontaneous speech obtained by the description of a photography. RESULTS: The
      intra and inter judges reliability are correct (intraclasse coefficient of 0.97
      and 0.98). The different parts of the test are well correlated to the reference
      proof (r = 0.75 to 0.82). Chronbach alpha is 0.98, the limits of agreement are
      14.88 +/- 3 on a maximum score of 88. The dispersion is enough for a good
      differentiation of the patients. (11 to 88, avec mean 62.93, SD 22.45) with a
      significant difference p < 0.002 between the control group and the population
      with speech disorders. CONCLUSION: This test constructed on the concept of a
      composite assessment is validated.

PMID- 21086655
TI  - [Preliminary experimental studies of whispered voice: subglottal pressure and
      postural aspects].
AB  - OBJECTIVES: Whispered voice is investigated from the energetic point of view. Our
      hypothese is that whispered voice, and mainly the forced whispers are very
      similar to vocal effort, for non acoustic vocal parameters, and body movements.
      DESIGN: Two experiments are combined. The first experiment focused on the
      laryngeal aspects, mainly the subglottal pressure, and also the
      electroglottography. The second experiment analyzed the body movements associated
      with loud whispered voice. RESULTS: No electroglottograhic wave was observed
      during the two experiments. The vocal intensity was always lower during whispered
      voice than during comfortable voice (p < 0.001). In experiment 1, subglottal
      pressure was significantly higher during forced whisper than during the other
      conditions (p < 0.001). In experiment 2, the amplitude of the trunk movements in
      the sagittal plane were greater during loud whisper than during comfortable voice
      (p < 0.001). CONCLUSION: Whispered voice can be close to vocal loading,
      especially the loud whispered voice.

PMID- 21086656
TI  - [The ultra-rapid cinematography of the larynx, its contributions in speech
      pathology].
AB  - The development in the medical field of high speed cinematography and its
      dissemination in the field of speech pathology will probably change the way we
      view the larynx and diagnose its disorders. So far only the stroboscope could
      inform us about the appearance of vocal cord vibration but with certain
      limitations. Indeed the wave motion of the vocal cords is really only apparent
      motion. It is made possible through the phenomenon of retinal persistence of
      images and light intermittent vocal folds set to the frequency of the voice and
      out of phase by a few Hertz. This technique has several disadvantages: The need
      for the voice to trigger the strobe light; a low number of frames per second (25
      fps) recorded; frame loss for the period between unlit two flashes; limitation in
      the study of the upper voice spectrum (gearing). The ultra-rapid cinematography
      brings a big difference in design since the digital recording can shoot up to
      4000 frames per second with permanent lighting of the larynx. The slow reading of
      short sequences permits us to view the actual movement of vibrating structures,
      and to analyze the behavior of the vibrator during the transitional phases of the
      attack, depreciation and termination of sound. The footage in high resolution
      permits a detailed analysis of the movements of opening and closing of the vocal
      cords in phonation and respiration, and the diagnosis of lesions.

PMID- 21086657
TI  - [Callas or the trajectory of the meteor].
AB  - The lyric career of Maria Callas, though exceptional, is also noteworthy for its
      brevity. The first signs of downturn appeared at the age of 36 and her voice fell
      silent at only 40. Though the literature has massively commented on this
      premature worsening, few analyses of its characteristics have been made public so
      far The purpose of our study was to realise a perceptual and acoustical analysis
      of recorded arias by the artist at the climax to the fall. The audible
      impairments were first verbally described, and then compared to acoustical
      observations based on spectrographic analyses and fundamental-frequency
      measurements.

PMID- 21086658
TI  - [Evaluation in clinical practice of the quality of life of patients with VADS
      cancer: an ethical justification or a fad?].
AB  - Now that the treatment of head and neck cancer has been perfectly standardized
      and the complications and sequelae are well known, many authors have started to
      investigate health-related quality of life (QoL). The use of generic and cancer
      specific QoL instruments remains limited to the field of research, but can this
      approach be transposed to clinical oncology? This study was designed to answer
      this question by identifying the ethical problems related to QoL assessment. The
      methodology used is based on a questionnaire survey of a cohort of 40 volunteer
      patients, conducted some time after their initial treatment in order to optimally
      assess their expectations and questions in relation to these aspects. The
      validity of the instrumental approach cannot be guaranteed due to conceptual
      limits, and the sociocultural level and cognitive state of the target population.
      A more subtle approach to QoL assessment in routine clinical practice would
      consist of a mixed approach harmoniously combining quantitative and qualitative
      aspects based on questionnaire and interview.

PMID- 21086659
TI  - [CT scan, MR imaging and anatomopathologic correlation in the glottic carcinoma
      T1-T2].
AB  - OBJECTIVES: Endoscopy and imaging are necessary to diagnose glottis carcinoma.
      Today, CT scan is the gold standard but MR imaging should be more sensitive for
      neoplastic invasion detection. The purpose of this study was to determine which
      exam to perform (CT scan or MRI) for neoplastic invasion. MATERIAL AND METHODS:
      This prospective study span a 18 months period. Seven patients with glottis
      carcinoma (TI-T2) underwent CT and MR imaging before surgery. Findings at imaging
      and pathologic examination were compared. RESULTS: Both CT and MR imaging were
      interesting, more specific (90%) than sensitive (74%). The anterior commissure,
      ventricles, subglottis, thyroid and arytenoid cartilages are the more difficult
      area analyzing. CONCLUSION: CT imaging stays the gold standard. MR imaging is
      more effective on second intention to refine the data. Indications are being
      improved, with complete cure and more preserved laryngealfunctions.

PMID- 21086660
TI  - [Partiturogram: (new) tool in the evaluation of an opera roles].
AB  - The partiturogram is a tool that was defined in the 1990s by Franco Fussi. It
      aims to display all the music notes of an opera role as a histogram. Several
      parameters are then calculated in order to define the vocal profile of the role,
      as well as help the singer choose from various options. We have decided to use
      this tool to study Norma and Sonnambula, two roles which were specifically
      written for the same singer described as a dramatic soprano. Over time, both
      roles have been allocated to radically different voices. The partiturogram
      confirms the similarity of the vocal types of both roles, but gives no
      explanation as to the differences in the casting decisions. We have therefore
      established its limits, and we have submitted a study including new parameters in
      order to refine the characterization of roles.

PMID- 21086661
TI  - [Evaluation of a dysphonic population. Interest of a therapeutic team composed by
      the phoniatrician and the speech therapist].
AB  - PURPOSE: To evaluate a population of dysphonic treated in rehabilitation by
      comparing the VHI score and GRB scale. MATERIALS AND METHODS: 300 questionnaires
      were completed, only 42 cases were matched before and after 15 rehabilitation
      sessions; that is 84 questionnaires. Patients were divided into two groups: group
      1 (impaired mobility of the vocal cords), group 2 (benign mucosal lesions). All
      patients completed a VHI questionnaire, a questionnaire evaluating subjective
      voice abuse (SSVS), a GRB score. The two tests were correlated to the diagnosis
      of voice pathology but also used for follow up after voice therapy. The tests
      used for statistical studies were: comparison by pathology by unpaired series
      tests (theoretical deviation=0); mean tests, Wilcoxon type. RESULTS: Patients
      were more handicapped by impaired mobility of the vocal cord than by a nodule or
      a cyst. The patients' vocal handicap (VHI) was significantly lower after 15
      therapy sessions, in all of its components. The perceptual evaluation GRB is also
      significantly better for these patients after 15 therapy sessions. We could not
      demonstrate a favorable evolution, that is a diminution of the SSVS before and
      after 15 sessions. CONCLUSION: The efficacy of speech therapy for certain vocal
      cord pathologies has been demonstrated both in respect of the Vocal Handicap felt
      by the patient as well as the Hirano scale.

PMID- 21086662
TI  - [Rehabilitation strategies of dysfunctional dysphonias in relation to posture].
AB  - OBJECTIVE: To improve rehabilitation strategies of functional dysphonias in
      relation to posture after clinical asssessment and recordings of posture obtained
      using a stabilometric platform and EquiTest. MATERIAL AND METHOD: 2 groups were
      compared: group 1 (58 dysphonic patients; 44 women and 14 men), group 2 (19
      nondysphonic singers; 11 women and 8 men). They all had a vocal assessment, a
      test of Freeman and an EquiTest. Their vocal handicap was evaluated by the Voice
      Handicap Index (VHI) and the WONCA questionnaire. The same assessment was
      repeated after rehabilitation. RESULTS: In dysphonic subjects before
      rehabilitation, the center of gravity during vocal projection and without vocal
      projection is rather off-set forwards and their postural stability is worse than
      the group 2 subjects. Vestibular information is less used with a less effective
      balance strategy. After vocal rehabilitation the voice is improved, vestibular
      information and the balance strategy are more effective. The VHI Score after
      rehabilitation goes from 40.36 to 26.35 for a total score of 120. CONCLUSION:
      Rehabilitation must be focused on the training of new gestures allowing better
      postural control thus releasing the phonatory potentials. This is actually
      possible with several known or modified exercises.

PMID- 21086663
TI  - [Definitely exciting].

PMID- 21086664
TI  - [Certified nurses turn their backs on full time jobs - DBfK shows politics the
      yellow card. "100 percent cannot be tolerated"].

PMID- 21086665
TI  - [Editorial board member comments on the decision of the nursing grade system: a
      welcome regulation!].

PMID- 21086666
TI  - [Crisis communication as a part of risk management: preventing lasting image
      damages].

PMID- 21086667
TI  - [Joachim Prolss shares insight into his responsibility as new director of nursing
      at UKE: "Here I can contribute at the top of the hierarchy as well" (interview by
      Ruth Mamerow)].

PMID- 21086668
TI  - [The process of organ donation: nurses are assigned a key role].

PMID- 21086669
TI  - [Special requirements for medical textiles: with silver ions against viruses and
      odor].

PMID- 21086670
TI  - [Extreme situations in nursing - peers support professionals: not abandoning
      nurses].

PMID- 21086671
TI  - [Transfer of the Maslow needs pyramid to inpatient geriatric nursing: promoting
      motivation].

PMID- 21086672
TI  - [Strategies of biography oriented simulated world construction: preventing stress
      and overload].

PMID- 21086673
TI  - [Value of the person centered approach for nursing culture: promoting trust based
      interactions].

PMID- 21086674
TI  - [Smoke free in nursing: breaking through the addiction spiral].

PMID- 21086675
TI  - [Will inpatient care still be financeable? Effects of the minimum wage to
      operators].
AB  - Due to demographic and social developments nursing service will continueto be a
      growth industry in the long run. The requirement for this is the political
      volition of a sufficient funding. A minimum wage in nursing service tends to
      increase prices of the offered services. Stated justifications for a minimum wage
      are wage dumping protection (inter alia against the background of the upcoming
      opening of the single market in 2011) as well as raising rivals' costs.
      Protection is focused on the 266,000 non-skilled workers in basic care owing to
      the strong tightening of the labour market for caregivers. Operative minimum
      wages will lead to adjustments by optimising operations, intensification of work,
      and rationalisation of workflow by increased employment of capital as well as
      technical substitution of relatively expensive non-skilled workers. In addition
      there will be increased pressure on prices for nursing services and private co
      payments. There will be an increased supply and demand for illegal services.
      Suppliers who had been tied to collective contracts so far will achieve a
      relative advantage in competition.

PMID- 21086676
TI  - [Decubitus ulcer in the malpractice process: fully controllable risk?].

PMID- 21086677
TI  - [Planning a practical instruction situation - 11: Nursing care of the newborn
      infant].

PMID- 21086678
TI  - [From case to case: staying on the safe side].

PMID- 21086679
TI  - [Recognizing and understanding illness: in focus: transitory ischemic attacks -
      TIA].

PMID- 21086680
TI  - [Controversial interpretations of the Lorsch medical codex].
AB  - Next to the late Heinrich Schipperges, Gundolf Keil, M.D. and Ph.D. (Medieval
      German), ranks as one of the foremost German medical historians of the Western
      Middle Ages. Among his lasting merits is the publication of the MS Bamb. med. 1,
      called by him Lorscher Arzneibuch (Lorsch Medical Manual), which was written
      during the first years of the 9th century in the abbey of Lorsch (near Worms).
      Keil maintained that this work was not only the first medical book copied in the
      German-speaking area but that it was also drawn up in Lorsch and contained e.g.
      an unequivocal statement of Carolingian health policy, and that it referred, for
      the first time in the early Middle Ages, to the therapeutic uses of penicillin,
      glycosides, and hypericin (an active ingredient of St John's wort). Such
      interpretations will be scrutinized and challenged in the following article.

PMID- 21086681
TI  - [Development and popularization of medical breastfeeding recommendations in
      twentieth-century Germany].
AB  - SUMMARY: Breastfeeding is considered to be the key variable for infant health.
      Consequently, UNICEF and the World Health Organization promote the beginning of
      breastfeeding within the first hour after birth and recommend to exclusively
      breastfeed the infant during the first six months. The origins of these modern
      breastfeeding campaigns can be traced back to the beginning of the twentieth
      century. Whereas high infant mortality rates traditionally were considered to be
      a matter of fate, declining birth rates towards the end of the nineteenth century
      raised fears about the nation's future and led to the emergence of an increasing
      infant welfare movement in Imperial Germany. As low breastfeeding rates were
      identified as a key factor behind the high infant mortality rates, the main
      objective of the infant care movement was to increase breastfeeding. The paper,
      therefore, focuses on medical breastfeeding recommendations and the attempts to
      popularize breastfeeding. At first, a sketch of medical doctrines will be
      presented, followed by a short survey of popular parental guidelines. Finally,
      two famous manuals of infant raising from the early twentieth century will be
      analysed in more detail. On the whole, the paper covers the period from the
      beginnings of social paediatrics at the beginning of the 20th century, the
      nutrition recommendations embedded into Nazi ideology during the Third Reich,
      until the declining breastfeeding ratios and the "feeding on demand"-movement in
      the 1970s as well as the ideological differences between West and East Germany
      during the Cold War.

PMID- 21086683
TI  - [Hypothyroidism is common in bile duct stone patients].
AB  - For decades, one well-known risk factor for the development of gallbladder stones
      has been hypothyroidism. Recent studies have reported that the risk for common
      bile duct stones particularly increases both in clinical and subclinical
      hypothyroidism. There are multiple factors that may contribute to the formation
      and/or accumulation of common bile duct stones in hypothyroid patients, including
      decreased liver cholesterol metabolism, diminished bile secretion, and reduced
      sphincter of Oddi relaxation. When treating patients with common bile duct stones
      or microlithiasis, the clinicians should be aware of the possible hypothyroid
      background, and consider the need for thyroid function assessment in these
      patients.

PMID- 21086684
TI  - [New antiarrhythmic drugs for treatment of atrial fibrillation].
AB  - Pharmacotherapy of atrial fibrillation (AF) is demanding, because currently
      available antiarrhythmic drugs have low efficacy and many side effects. In drug
      development, the focus has been on amiodarone-like multichannel blockers, atrial
      specific ion channel blockers, and novel non-channel agents targeting atrial
      remodelling. Dronedarone, an amiodarone analogue without iodine, was recently
      approved for treatment of AF. It is less effective than amiodarone, but serious
      adverse events are rare. Vernakalant, an atrial-selective drug with low
      proarrhythmic risk, is effective in cardioversion and it may also prevent AF
      recurrences. So-called upstream therapy with angiotensin converting enzyme and
      angiotensin receptor inhibitors, statins and omega-3 fatty acids needs further
      clinical validation.

PMID- 21086685
TI  - [Quality of life of psychiatric patients].
AB  - Quality of life is difficult to define and utilizes hundreds of indicators partly
      arriving at different results. By measuring losses of the quality of life,
      general psychiatric disorders compare with the most severe chronic somatic
      diseases. The effects of anxiety and affective symptoms are major, calling for
      more attention on their treatment. Patients with schizophrenia often have life
      quality assessments that are more positive than those of the surrounding people,
      a fact that should be considered in setting of the objectives of their treatment.
      The losses of the quality of life of the patients' close relatives should also be
      taken into account.

PMID- 21086682
TI  - [Incidence, treatment and prognosis of acute respiratory failure in Finland--the
      FINNALI study].
AB  - In a cohort study covering whole Finland, the incidence of acute respiratory
      failure was higher than in previous international studies. The number of patients
      fulfilling the diagnostic criteria for acute lung injury and acute respiratory
      failure remained, however, smaller than that reported in international
      comparative data. The 90-day mortality was 31% and one-year mortality 35%.
      Recommended airway pressure levels were followed in ventilatory support
      treatment, but tidal volumes were larger than those in recent therapeutic trials.
      Patients outcome could probably be further improved by centralizing intensive
      care services.

PMID- 21086686
TI  - [Determination of troponin].
AB  - The determination of troponin from a blood sample is the most sensitive means to
      prove a recent myocardial injury. An elevating troponin level associated with
      acute coronary syndrome indicates an increased risk of death and reinfarction,
      serving as an indication for an invasive investigation of coronary anatomy.
      Troponin is also frequently elevated in injuries not caused by cardiac
      infarction. The use of troponin should be focused on situations involving a
      suspicion of myocardial ischemia on clinical grounds. We analyzed the causes of
      an elevated troponin level from the emergency discharge diagnoses of 301 patients
      referred to internal medicine emergency.

PMID- 21086687
TI  - [Update on current care guidelines. Parkinson's disease].
AB  - Following the diagnosis of Parkinson's disease, treatment may be initiated with
      MAO-B-inhibitor, even prior to the development of any functional deficit. For
      patients with a functional deficit who are younger (usually under 75 years of
      age) and otherwise in good condition, treatment should be started with a dopamine
      agonist or MAO-B-inhibitor. In other patients, initial treatment with levodopa is
      recommended. In the case of difficult on-off-symptoms and dyskinesias in spite of
      optimal treatment, surgical procedures and duodenal levodopa infusion should be
      considered. Rehabilitation should be targeted at specific problems associated
      with functional skills.

PMID- 21086688
TI  - [Genetics of multifactorial diseases].
AB  - Multifactorial diseases refer to diseases having a genesis known to be influenced
      both by the genome and the environment. Examples include cardiovascular diseases,
      asthma, autoimmune diseases and various neurological and psychiatric diseases.
      Technical development has made possible a considerably more accurate measurement
      of genetic variation, having already led to the identification of hundreds of
      predisposing genes. We do not, however, still understand enough about the
      mechanisms of action of genes. The increasing progress in DNA sequencing
      techniques is currently changing the prospects of research more quickly than ever
      before.

PMID- 21086689
TI  - [Finnish disease heritage].
AB  - The Finnish disease heritage refers to rare hereditary diseases that occur in the
      Finnish population in a relatively larger proportion than in other populations.
      The genes underlying all of the 36 diseases of the disease heritage have been
      identified. Together with her group and collaborators, Leena Palotie identified
      15 of these, and this review includes the description of some of these
      achievements. As a result of the so-called founder effect, one predominant
      mutation underlying these diseases occurs in our population, facilitating the
      diagnostics of these diseases in our country.

PMID- 21086690
TI  - [From fingerprints to DNA tags].
AB  - Decisions concerning individuals are made based on the DNA fingerprinting
      technique, e.g. in the courts of law. Currently applied DNA markers and the
      technique associated with their analysis have changed significantly from those of
      the original DNA fingerprint. The digital nature of today's DNA tag determination
      has enabled the application of powerful DNA registers in crime investigations.
      Application of DNA tags has expanded from paternity, crime and cadaver
      identification to the prediction of external features such as hair or eye color
      in criminal investigation. In the early 1990's pioneering work on PCR-based DNA
      identification was carried out in Finland.

PMID- 21086691
TI  - [Role and integration of technical prevention figures in the management system].
AB  - The multifarious issues of health and safety at work require multi-disciplinary
      skills, both in the risk assessment and in the subsequent definition and
      management of preventive measures, and this requires a renewed operational
      protocol that supports integration and co-operation between the technical
      prevention figures. Thus, between occupational physicians and technical advisers
      there should be a concrete and fruitful interaction, which should not be episodic
      or occasional, but a modus operandi systematic and constant. In this contribution
      is discussed as the technical prevention figures should be included in the Health
      and Safety Management System and should make a specific contribution in defining
      corporate policies on prevention. In particular it is outlined the role that the
      occupational physician may play in the development of prevention and health
      promotion activities within the strategies of corporate social responsibility.

PMID- 21086692
TI  - [The occupational physician and communication to workers].
AB  - Communication ability is essential for the Physician to the proper management of
      ambulatory activity and corporate training. The aim of this work is describe the
      communication strategies to be adopted in everyday healthcare practice. When the
      occupational physician relates with an employee his message must act both verbal
      both non-verbal. The medical history should be collected carefully and during the
      physical examination is important to put the employee at ease by adopting a
      discreet and attentive attitude. The clinical findings and the capacity to work
      with any limitations will be discussed at the end of health surveillance using
      understandable terminology to the worker. During the training-information process
      is important to define the primary objectives, organize the program and bring the
      display materials. The worker should be actively involved and encouraged to learn
      throughout the course information. In the text will also be shown the main
      aspects of information on line.

PMID- 21086693
TI  - [The development of organizational comfort: organizational training as strategic
      instrument for changing].
AB  - The organizational comfort has been defined as the relationship between people
      and work environment. The supervisor's functions imply organizing and relation
      competences, listening and observation, communication and negotiation.
      Unfortunately, the reality is quite different: there are often situations of
      communication disorder between the supervisor and the worker, where the first,
      unaware of his role and responsibility, doesn't understand the worker's needs,
      doesn't communicate rightly the risk, doesn't develop any emphatic attitude and
      organize work without thinking to individual inclinations and limitations. The
      worker perceives this situation as increasing sensation of tiredness and working
      stress. The workers, often involved in this organization, have to ask overtime
      medical examinations to obtain some limitations. Observing this big increase of
      limitations in some firms with working people relatively young, we have decided
      to elaborate an experimental project involving both the occupational doctor and
      the psychologist. We analyzed the relations between the supervisor and the
      worker, with the aim to increase organizational comfort, through the diffusion of
      anonymous questionnaires or training courses about behaviour analyses and
      communication strategies, verifying any possible modifications of the
      organization after our intervention.

PMID- 21086694
TI  - [Managment system in safety and health at work organization. An Italian example
      in public sector: Inps].
AB  - The Istituto Nazionale della Previdenza Sociale (Inps) is one of the biggest
      Public Sector organizations in Italy; about 30.000 people work in his structures.
      Fifteen years ago, Inps launched a long term project with the objective to create
      a complex and efficient safety and health at work organization. Italian law
      contemplates a specific kind of physician working on safety and health at work,
      called "Medico competente", and 85 Inps's physicians work also as "Medico
      competente". This work describes how IT improved coordination and efficiency in
      this occupational health's management system.

PMID- 21086696
TI  - [Techniques of communication and information-formation of the workers].
AB  - Communication has always had a very important role among human activities.
      Communication is: a Source sending a Message to an Addressee within a Context
      through a Contact thanks to a Code. In 1965 Umberto Eco developed the concept of
      Aberrant Decoding that is the wrong decoding of the message by the addressee. As
      to communication D.Lgs81/08 e s.m.i. fixes the following rules. Information of
      workers (Art. 36/1)--The employer is responsible for the workers to have the
      right information about risks for health and safety in their specific workplaces,
      etc. Formation of workers (Art 37/1)--The employer is responsible for the workers
      to have adequate and proper formation as to health and safety with regard to
      linguistic knowledge. Therefore it is really important for a Company to establish
      real communication between management and workers and among workers, to have a
      frequent feedback and to let information circulate in order to have all safety
      regulations followed properly.

PMID- 21086695
TI  - [Communication skills and their influence on prevention strategies in workplace].
AB  - Communication is a process which enables groups and individuals to increase their
      control over determining health factors acting on people's lifestyles to promote
      health. Good communication is fundamental to the health sector in a globalized
      world, since it may influence national and local policies, health promotion
      campaigns and correct operational practices. Our study analyses four significant
      incidents related to instances of bad communication and covers questions which
      have produced rather incoherent results provoking unjustified alarm. It is
      therefore necessary to prescribe a way of approaching these issues which will
      firstly lead to a more careful analysis of the risk involved and therefore to
      make known correct public information. It is necessary to improve the skills of
      experts in prevention, to promote educational initiatives at school, universities
      and in workplaces always focussing more on interdisciplinarity and developing new
      ways of approaching problems concerning health and safety.

PMID- 21086697
TI  - [Organizational and management companies models].
AB  - With the legislative decree 81/08 and s.m.i. it's explicitly defined a model of
      management and corporate organization that can contribute to prevent security
      risks in work environments. The realization of the model is not obligatory, but
      desirable because the result of its implementation is a decrease of company's
      risks and costs for safety. Our study group has developed the structure of an
      organizational and management model for corporate safety and the tools necessary
      for its realization. The realization of a model is structured in various phases:
      initial exam, safety policy, planification, implementation, monitoring, system
      retest and improvement. Such a model, in continuous evolution, is based on the
      responsibilities of the different corporate figures through an accurate analysis
      of the measured risks and the measures adopted.

PMID- 21086698
TI  - [Regional programs and opportunities for the occupational health physician].
AB  - It is a well known fact that, in amending, Title V of the Italian Constitution,
      constitutional law no. 3/2001 inserted "Workplace health and safety" in paragraph
      3 of article 117 as an issue assigned to the legal competence of regional
      governments. In this perspective, the role to be played by the regional
      governments, with due regard for the restrictions of national laws, is both broad
      and composite. Firstly, it is a active participatory role in the formulation of
      national legislation through the permanent conference for relations between
      central, regional and autonomous provincial governments. A second important level
      is adaptation, via the regional laws passed by the national parliament, to local
      economic and productive contexts. Thirdly, there is the planning and
      coordination, via the regional committees set up specifically for this purpose,
      of all health and safety measures.

PMID- 21086700
TI  - [Professional activity of "competent physician": actual troubles and future
      perspectives].
AB  - In recent years, Health has experienced a great transformation, due to the latest
      technological breakthroughs, the discovery of new drugs and changing social and
      economic conditions of our country. The professional activity of the "competent
      physician", even, from the definition of art. 33 of DPR 303/56, result in today's
      complex set of procedural formalities that make your role as a great professional
      and social responsibility. However, there are still areas of uncertainty in the
      law and different interpretations that make it difficult to work. The competent
      physicians faced with a series of problems that hinder the development of their
      work, instead, should be free from interference in order to always get the
      expected results in preserving the worker's health. After a brief discussion of
      the main weaknesses found, are made some concrete proposals to ensure that the
      physician in the foreseeable future is increasingly a qualified professional
      capable of responding adequately to the needs arising from modern scientific
      evidence and the expectations of workers and the whole society.

PMID- 21086699
TI  - [Ideas, reflections and tools for a modern role of the occupational physician].
AB  - Over the last few years, following new legislations, events of media impact,
      transitions in workplaces, Occupational Medicine is at stake. Often, debate is
      strong about technical-scientific issues in Occupational Physician (OP)
      activities, ethics and deontology, professional independence, dignity, training
      and education. The present work develops through personal thoughts, literature
      data, reporting of concrete personal experience across various occupational
      settings and risks, with the aim of promoting a "new" role for the OP, enhance
      his autonomy, professional skills, uniqueness, quality, credibility, while being
      convinced that it is certainly necessary and possible to conjugate ethics and
      scientific approach within daily professional activity of the OP, who in turn
      should be prone to change pace, evaluate effectiveness of his actions, abandon
      obsolete and useless practices, focussing on a new, proactive, clinical
      diagnostic and managerial role, through good medical practices.

PMID- 21086701
TI  - [The Occupational Doctor working in private services appointed by the employer
      for medical surveillance (Law Decree 81/08, article 39 paragraph 2 letter a):
      professional, organisational, juridical and forensic implications].
AB  - The Italian Health and Safety Law (D.Lgs. vo 81/08) allows the Employer to commit
      to a private H&S Service the execution of the medical surveillance, being the
      Occupational Doctor ("Medico Competente") an Employee or Collaborator of the
      Service itself rather than a "freelancer" Professional. The implications of such
      a choice are discussed, taking in account the point of view of the Employer, the
      Occupational Doctor and the Control Authority.

PMID- 21086702
TI  - [The occupational physicians' responsibilities].
AB  - Occupational physicians can commit two kind of crimes: they can violate rules of
      safety and health at work with no immediate consequences for the employees but
      anyway creating a potential danger for them, or they can cause, because of their
      blame, occupational diseases or accidents at work to the employees. In both cases
      they can be punished. If we want to understand in detail this kind of
      responsibility, we must read the Supreme Court's judgements (Supreme Court,
      19099/2009; 26539/2008; 20220/2006; 17838/2005; 26439/2007; 24290/2005). The
      numberless innovations introduced in recent years in the body of occupational
      safety and health laws called for a different reading of the meaning and the
      content of occupational physicians' functions, requiring them to collaborate,
      more than in the past, in the assessment of workplace risks. The responsibility
      of occupational physicians should be seen also in relation to the responsibility
      of employers and managers (see the link between health surveillance and art. 18
      paragraph 1 letter c) of Legislative Decree no. 81/08). In the occupational
      safety and health context, the employer and his managers must also require (and
      ensure) occupational physicians to fulfill their obligations and professional
      duties.

PMID- 21086703
TI  - [Shift work and breast cancer].
AB  - The International Agency on Research on Cancer (IARC) has recently classified
      "shiftwork that involves circadian disruption" as "probably carcinogenic to
      humans" (Group 2A) on the basis of "limited evidence in humans for the
      carcinogenicity of shift-work that involves nightwork", and "sufficient evidence
      in experimental animals for the carcinogenicity of light during the daily dark
      period (biological night)". The epidemiologic evidence of a relationship between
      shift and night work and breast cancer in women is based upon nine studies, six
      of which suggest a moderately increased risk to develop breast cancer after
      prolonged exposure to shift and night work. The aim of this paper is to summarize
      the possible physio-pathological mechanisms (internal disruption of biological
      circadian rhythms and clock genes, melatonin suppression through light by night,
      sleep deprivation) and the problems connected with a proper risk assessment of
      the risk for breast cancer risk in women shift workers.

PMID- 21086704
TI  - [Protection of working woman's health].
AB  - INTRODUCTION: In the past the role of women was mainly that of wife and mother,
      over the centuries, this role has changed: women assert themselves in every
      social field and workplace. OBJECTIVES: Analyze the history of women's work, from
      prehistory to the present day highlighting the evolution of women's role over the
      centuries. Identify which may be the different occupational stressors, in
      particular the organizational and psycho-social ones, to which is submitted a
      working woman. MATERIALS AND METHODS: The authors have analyzed the most relevant
      data from literature, in particular on the issue of mental health. RESULTS:
      Provide the main forms of prevention that have to be implemented. DISCUSSION: The
      main challenge for women today, is to balance work outside the home and
      housework. This added to job stressors, may interfere with the psychological and
      physical wellbeing of the worker.

PMID- 21086705
TI  - [Endocrine disruptors and reproductive health].
AB  - Endocrine disruptors (EDs) are dangerous chemicals widely used daily and spread
      in the environment and able to impair male and female fertility by interfering
      with the endocrine regulation of reproductive system. Many epidemiological
      studies showed the role of the EDs in the pathogenesis of reproductive
      pathologies such as infertility, recurrent abortions, malformations and
      endometriosis. Personal data show a significant correlation between phthalates
      and bisphenols and endometriosis. Further studies are needed to assess a clear
      relationship between environmental exposure to ED and reproductive pathologies
      and to find exposure's markers for environmental pollutants in biological fluids
      with the aim to have useful instruments for monitoring and preserving the
      reproductive health of women at risk of occupational/environmental exposure to
      ED.

PMID- 21086706
TI  - [What are the causes and the reason why of diseases prevalence and incidence in
      occupational sample of women].
AB  - Aim of this study has been the evaluation of health status change among women and
      men engaged in different occupational activities. METHODS: In a sample of 1,145
      women and 3,110, collected in a time span of 10 years, were calculated prevalence
      and incidence of diseases related to occupational and non occupational variables:
      physical work load and job timing, civil status and family engagement.
      Differences between sexes were calculated by X-square and mean difference test.
      RESULTS: In women subset, cardiovascular and vertebral degenerative disease,
      skin, wrist and elbow (carpal canal and epicondylitis) pathologies were much more
      represented than in men's ones. Psychiatric and psychosomatic symptoms and
      diseases were much more represented in the women sample and furthermore at
      younger age. In women, heavier work load has been the most responsible factor of
      degenerative diseases, while shift work of psychiatric and psychosomatic
      diseases. In the same gender, the stable living together and family charge
      increased the incidence of chronic degenerative diseases, suggesting an
      empowering effect coming from the occupation. In conclusion, from data analysis
      it is possible to speculate that working women's health profile is sensible to
      various determinants with synergic effect; consequently the clinical emergence of
      diseases is shown up earlier.

PMID- 21086707
TI  - [Gender at work: from theory to practice].
AB  - INTRODUCTION: In Italy a recent legislation introduced norms concerning gender
      based risk assessment. METHODS: Collection of recent european and international
      publication and network Congresses on gender. RESULTS: Italy has now the
      scientific knowledge to start a gender oriented risk assessment. DISCUSSION:
      Gender sensitive good practices can represent a good way to improve women working
      conditions in Italy

PMID- 21086708
TI  - [Angiotensin II type 1 receptor blockade and risk of cancer].

PMID- 21086709
TI  - Bariatric surgery in Finland - quo vadis?

PMID- 21086710
TI  - How to prevent glucocorticoid-induced osteoporosis.

PMID- 21086711
TI  - [Should fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity
      be treated in psychiatric services? 3].

PMID- 21086712
TI  - Thrombolysis: attempting to reduce postcode prescribing in Scotland?
AB  - The literature is littered with reports presenting the proportion of patients
      admitted with ischaemic stroke receiving thrombolysis. This gives some measure of
      activity and the efficiency of prehospital and hospital triage. Some stroke
      centres have reported rates of thrombolysis as high as 20%, but without knowing
      the population that such services serve, these proportions do not indicate how
      well or equitably the treatment is being delivered. Here, we explore various
      metrics to monitor our efforts to provide equitable access to stroke thrombolysis
      in Lothian, a region in the South East of Scotland.

PMID- 21086713
TI  - Hypothermia for Stroke: call to action 2010.
AB  - The European Hypothermia Stroke Research Workshop was held in January 2010, in
      response to the alarming prospects of a significant increase of stroke expected
      in the coming years globally. Considering that a minority of patients (around
      10%) are currently eligible for thrombolytic treatment, there is a need for an
      efficacious, cost-effective novel therapy that can be implemented broadly within
      European health care systems. Accordingly, the primary objective of the workshop
      was the definition of a research agenda aiming to assess the therapeutic benefits
      of hypothermia in patients with acute ischaemic stroke. The meeting was organised
      by the European Stroke Research Network for Hypothermia (EuroHyp) and attended by
      the representatives of World Stroke Organisation, European Stroke Organisation,
      Stroke Alliance for Europe, Society for Cryobiology and other organisations-
      specifically the European Space Agency, and small- and medium-sized enterprises
      based in EU member states. The participants adopted the 'Hypothermia for Stroke-
      Call to Action 2010', a declaration specifying the priorities for hypothermia
      research in acute ischaemic stroke. The research programme outlined--a clinical
      study programme designed to identify and validate therapeutic cooling as a novel
      treatment providing benefit to a large number of stroke patients--contains a well
      integrated series of Phase II studies aiming to refine the intervention (depth,
      duration, and mode of cooling; antishivering strategy; patient selection) and a
      pivotal Phase III clinical trial. The proposed integrated Phase II and III
      clinical study programme would test the effectiveness of this optimised
      intervention, and would allow the development of evidence-based Clinical Practice
      Guidelines describing the optimal use of therapeutic hypothermia as a treatment
      strategy for stroke.

PMID- 21086715
TI  - [Mammography screening saves life].

PMID- 21086714
TI  - [Rely on your back].

PMID- 21086716
TI  - Dominant T-cell epitopes of filarial BmALT-2 and their cytokine profile in BALB/c
      mice.
AB  - Filarial nematodes down-regulate the host immune response to establish infection
      by inducing IL-10-mediated T-cell suppression.Abundant larval transcript (ALT)
      proteins are of major interest as they are expressed abundantly in the L3 stage,
      implicated in protective immunity and may play a role in immune evasion. The T
      cell epitopes of BmALT-2 and the cytokine responses induced by these peptides
      were investigated in a mouse model using synthetic peptides, which could be
      exploited in the design of a potent epitope-based vaccine. Five regions were
      found to carry T-cell epitopes inducing high levels of cellular proliferation.
      The regions 55-68 and 73-91 of ALT-2 induced very high levels of IL-10 secretion
      and hence could be involved in immunomodulation in the host.

PMID- 21086717
TI  - SerpinB2 deficiency modulates Th1/Th2 responses after schistosome infection.
AB  - SerpinB2, also known as plasminogen activator inhibitor type-2, is a major
      product of macrophages and is upregulated during many infections. Although
      SerpinB2 inhibits urokinase plasminogen activator in vitro, evidence that this
      represents its physiological role in vivo is not compelling. We have recently
      shown that SerpinB2-/-mice generate enhanced Th1 responses after immunization
      with a Th1 immunogen. Herein,we show that Schistosoma japonicum granulomas
      induced liver SerpinB2 mRNA expression by >600-fold in wild-type mice. In
      SerpinB2-/- mice, worm and egg burden, and granuloma number and volume were
      unaffected. However, granulomas in these mice were associated with reduced
      fibrosis (as determined by Sirius red staining and image analysis) and increased
      iNOS, IL-6, IL-10 and TNFa and decreased Arg 1 and IL-13 mRNA expression.
      SerpinB2-/- mice immunized with soluble egg antigen (SEA) also showed reduced
      levels of SEA-specific IgG1. SerpinB2 deficiency thus promoted certain Th1 and
      reduced certain Th2 responses in response to this Th2 immunogen.

PMID- 21086718
TI  - The expression of TLR9 in human cutaneous leishmaniasis is associated with
      granuloma.
AB  - The Toll-like receptor (TLR) signalling pathway is the first system that defends
      against Leishmania. After recognising Leishmania as nonself, TLRs trigger NF
      kappaB expression.NF-kappaB proceeds to the nucleus and promotes the
      transcription of pro-inflammatory cytokines. TLR9 is thus an important factor in
      the induction of an effective immune response against Leishmania. We examined the
      pattern of TLR9 expression in 12 patients with cutaneous leishmaniasis caused by
      Leishmania braziliensis detected by polymerase chain reaction. Normal skin was
      analysed as a negative control. TLR9 expression was examined in the dermis and
      epidermis by immunohistochemical analysis of paraffin-embedded biopsy tissue.
      TLR9 expression was primarily observed in the granuloma. The protein was detected
      in a few cells in the dermis. A lower expression level was detected in the
      epidermis of patients with leishmaniasis when compared with normal skin. The
      presence of TLR9 in the skin of patients with cutaneous leishmaniasis is
      associated with granuloma and expressed by macrophages.

PMID- 21086719
TI  - Caspase-12 deficiency enhances cytokine responses but does not protect against
      lethal Plasmodium yoelii 17XL infection.
AB  - To investigate the effect of caspase-12 deficiency on IFN-gamma- independent
      control of blood-stage malaria, we compared lethal Plasmodium yoelii 17XL
      infection in wild-type C57BL / 6J and caspase-12-/-mice. Infected caspase-12-/-
      mice exhibited higher parasitaemia than WT mice on days 8 and 9 post-inoculation,
      but all WT and caspase-12-/- mice succumbed by day 10. In addition, infected
      caspase-12-/-mice had significantly elevated levels of IFN-gamma, TNF, IL-18,and
      IL-10 in sera compared to infected WT mice. At the terminal stage of disease,
      there were no differences in cytokine levels in the tissues of infected WT and
      caspase-12-/- mice. However, liver pathology was more severe in infected caspase
      12-/- mice compared to infected WT mice. Together, these findings indicate that
      although caspase-12 deficiency results in enhanced pro-inflammatory and
      immunoregulatory cytokine levels in sera during P. yoelii 17XL infection, these
      responses are not essential for protection against lethal malaria infection.

PMID- 21086720
TI  - Cathepsins: fundamental effectors of endolysosomal proteolysis.
AB  - Intracellular protein degradation is a universal feature of eukaryotic cells and
      vital for nutrition, protein turnover, intracellular signaling, development and
      other major physiological processes like antigen presentation and immunity. One
      of the major compartments of intracellular proteolysis is the endosome-lysosome
      system. The latter offers a highly orchestrated, vesicular pathway for protein
      transport and ultimate degradation in lysosomes. Though lysosomes are the
      classical organelles of complex, multi-enzymatic degradation, it is increasingly
      evident that endosomes conduct much more than mere transport functions. Endosomes
      contain significant levels of proteases like cathepsins and are sites of potent
      intracellular proteolysis. Further, discrete classes of endosomes harbor specific
      cathepsins and perform selective and exclusive functions. Hence, extra-lysosomal
      proteolytic machinery within the endocytic pathway enjoys spatial and temporal
      control over proteolytic functions. The review outlines the structural
      association and function(s) of major endolysosomal cathepsins.

PMID- 21086721
TI  - Optimized conditions for high-level expression and purification of recombinant
      human interleukin-2 in E. coli.
AB  - Interleukin-2 (IL-2), a potent cytokine has been used in anti-cancer therapy for
      over a decade now. IL-2, originally identified as a growth factor for T
      lymphocytes is a 15 kDa hydrophobic glycoprotein that induces the activation,
      clonal proliferation and differentiation of T and B-lymphocytes and enhances the
      cytotoxicity of monocytes and natural killer (NK) cells. Here, we report a simple
      method for the cloning, high-level expression and purification of IL-2 protein,
      which can be easily extended to other bioactive therapeutic proteins. The IL-2
      gene was amplified from human spleen cDNA and cloned in a prokaryotic (E. coli)
      expression system. An optimal expression of the IL-2 protein was determined by
      varying the expression conditions like temperature, inducer concentration and
      duration of induction. The protein was expressed as inclusion bodies and a panel
      of reagents including detergents, urea and guanidine hydrochloride were used to
      solubilize it. After solubilization, the protein was renatured and subjected to a
      single step gel-filtration chromatography to yield immunobioactive IL-2 protein
      with > 99% purity.

PMID- 21086722
TI  - Optimized expression, solubilization and purification of nuclear inclusion
      protein b of cardamom mosaic virus.
AB  - All RNA viruses encode an RNA-dependent RNA polymerase (RdRP) that is required
      for replication of the viral genome. Nuclear inclusion b (NIb) gene codes for the
      RdRp in Potyviridae viruses. In this study, expression, solubilization and
      purification of NIb protein of Cardamom mosaic virus (CdMV) is reported. The
      objective of the present study was to express and purify the NIb protein of CdMV
      on a large scale for structural characterization, as the structure of the RdRp
      from a plant virus is yet to be determined. However, the expression of NIb
      protein with hexa-histidine tag in Escherichia coli led to insoluble aggregates.
      Out of all the approaches [making truncated versions to reduce the size of
      protein; replacing an amino acid residue likely to be involved in hydrophobic
      intermolecular interactions with a hydrophilic one; expressing the protein along
      with chaperones; expression in Origami cells for proper disulphide bond
      formation, in E. coli as a fusion with maltose-binding protein (MBP) and in
      Nicotiana tabacum] to obtain the RdRp in a soluble form, only expression in E.
      coli as a fusion with MBP and its expression in N. tabacum were successful. The
      NIb expressed in plant or as a fusion with MBP in E. coli can be scaled up for
      further work.

PMID- 21086723
TI  - Optimized culture conditions for bacteriocin production by Pediococcus
      acidilactici LAB 5 and its characterization.
AB  - A strain of Pediococcus acidilactici LAB 5 was isolated from vacuum-packed
      fermented meat product, in order to obtain a novel bacteriocin from food-grade
      organisms. Optimized culture conditions for bacteriocin production in different
      media (viz., MRS, TGE, TGE + buffer, TGE + Tween 80, and TGE + Tween 80 + buffer)
      and at different temperatures and pH conditions were reported. TGE + Tween 80 +
      buffer medium was found to be most effective for bacteriocin production (about
      2400 AU/ml) by this strain, when incubated at 37 degrees C for 24 h. Bacteriocin,
      partially purified by adsorption-desorption method showed molecular mass of 10.3
      kDa and produced prominent inhibition zone in activity gel. It showed significant
      storage stability both at high as well as in low temperatures for up to 6 months
      and retained its activity in a number of organic solvents, except in 2
      mercaptoethanol. The treatment with amylase and lysozyme did not change its
      activity, but it lost its activity on proteinase K treatment. Antibacterial
      efficacy of bacteriocin was proved against some food spoilage and human
      pathogenic bacteria like Enterococcus, Leuconostoc, Listeria, Staphylococcus and
      Streptococcus.

PMID- 21086724
TI  - Co-immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase and
      peroxidase on to aryl amine glass beads affixed on plastic strip for
      determination of triglycerides in serum.
AB  - Commercial lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and
      peroxidase (POD) have been co-immobilized covalently on to arylamine glass beads
      affixed on a plastic strip through diazotization with a conjugation yield of 89.1
      mg/g support and 64.1% retention of specific activity. The co-immobilized enzymes
      showed maximum activity at pH 7.5, when incubated at 40 degrees C for 20 min. The
      strip was employed for determination of serum triglycerides (Tgs). The minimum
      detection limit of the method was 0.20 mM/L. The recovery of added Tgs was 88.0%.
      Within day and between day coefficient of variations were <7.0 % and <11.0%,
      respectively. A good correlation (r = 0.982) was observed between total serum Tgs
      values obtained by present method and the most commonly used enzymic colorimetric
      method, employing free enzymes. Among the various serum substances tested at
      their physiological concentrations, only cholesterol, ascorbic acid and bilirubin
      caused 30%, 15%, and 20% inhibition of strip-bound enzymes, respectively. The
      strip lost 50% of its activity after 150 regular uses over a period of 33 days,
      when stored in reaction buffer at 4 degrees C. The method reported here has the
      advantage over other existing methods, as it provides higher sensitivity, better
      stability and reusability of co-immobilized enzymes and is also economical.

PMID- 21086725
TI  - Genetic screening in couples experiencing recurrent assisted procreation failure.
AB  - Infertility is a major health problem affecting about 10-20% of couples in the
      reproductive age group. Male factor is assumed to be responsible in about 50%
      cases of infertility. The origin of reduced testicular sperm function is unknown
      in about 50-70% of cases and for such couples assisted reproduction techniques
      (ART) are a boon. Male infertility is often due to poor semen quality and may be
      associated with genetic defects. ART has revolutionized management of infertility
      and intracytoplasmic sperm injection (ICSI) is the ART procedure of choice in 60
      80% cases. Despite major technological advancements and professional expertise in
      ART, the success rate and carry-home live birth rate of ICSI is low (18-25%).
      This study was aimed to understand the genetic etiopathology of recurrent ART
      failure. For this, 110 couples with 3 or more failed ART cycles were recruited. A
      detailed history was taken and only idiopathic ART failure cases were enrolled
      for this study. They were subjected to cytogenetic and Yq microdeletion analysis.
      Genetic abnormalities were detected in 19 couples. Since a large number (18.2%)
      cases harboured genetic abnormalities, it is important for all couples opting for
      ART to undergo a thorough genetic analysis to prevent recurrent emotional,
      physical and financial stress.

PMID- 21086727
TI  - Mitochondrial complex I impairment and differential carbon monoxide sensitivity
      of cytochrome c oxidase in wild type and CMS II mutants of Nicotiana sylvestris.
AB  - Plant mitochondria unlike their animal counterpart have some unique features with
      highly branched respiratory chain. The present work was undertaken in order to
      investigate the effect of loss/dysfunction of plant mitochondrial complex I on
      the relative flux of electrons through alternative oxidase (AOX) and cytochrome
      oxidase. Loss of a major subunit of mitochondrial complex I in cytoplasmic male
      sterile II (CMS II) mutant of Nicotiana sylvestris caused respiratory redox
      perturbations, as evident from the differential CO sensitivity of cytochrome
      oxidase. The leaf segments of CMS II mutant when exposed to CO under dark aerobic
      condition were insensitive to the inhibition of cytochrome oxidase, as against
      the wild type (WT). The differential CO response of WT and CMS II mutants
      appeared to be due to differences in the redox state of cytochrome a3 (cyt a3),
      the terminal electron acceptor during in situ respiration. Cyt a3 appeared to be
      more in its oxidized form in CMS II and hence unable to form cyt a3-CO complex.
      Pre-treatment of CMS II leaves with 2,4-dinitrophenol, an uncoupler of oxidative
      phosphorylation increased the CO response. The slight increase in rotenone
      insensitive respiration of CMS II could be attributed partly to enhanced flux of
      electrons through cytochrome pathway to compensate for the loss of
      phosphorylation site and partly through AOX, which was induced by nitrate.

PMID- 21086726
TI  - Identification and partial characterization of juvenile hormone esterase from
      cotton pest Dysdercus cingulatus.
AB  - Juvenile hormone esterase (JHE), a selective enzyme that hydrolyzes the methyl
      ester of insect juvenile hormone plays an important role in regulating
      metamorphosis in nymphs as well as reproduction in adults. Studies on JH
      degradation provide insight into the possibilities of physiological disruption in
      the insects. In the present study, the JH degrading enzyme, JHE from the cotton
      pest Dysdercus cingulatus (Heteroptera) is characterized. Electrophoretic
      analysis of haemolymph during various developmental stages showed the JHE bands
      prominent only on the final day of 5th instar nymph, and the esterase substrate
      specificity confirmed the presence of JHE isoforms. In an attempt to clone cDNA
      of JHE gene from the final instar nymphs, mRNA isolated from fat bodies was
      coupled with JHE gene-specific primers and the cDNA was synthesized using RT-PCR.
      The PCR amplified cDNA showed the presence of JHE isoforms in D. cingulatus.

PMID- 21086728
TI  - SFRR-India satellite meeting report 2008.

PMID- 21086729
TI  - Brain tumors and epilepsy.
AB  - Brain tumors are a common cause of epilepsy. Tumor type and location are
      determining factors that significantly influence seizure frequency. The aim of
      this study was to analyze clinical data of patients diagnosed with brain tumors
      and epilepsy. Data for this study were obtained from patient medical records over
      a 6-year period (2000-2005). Patient history and findings obtained by diagnostic
      methods such as electroencephalography, computerized tomography and magnetic
      resonance were analyzed. Data were analyzed by appropriate statistical methods
      and the structure, prevalence, mean and standard deviation were calculated. The
      significance of results was tested by use of t-test and chi2-test. A total of 15
      933 patient charts were analyzed. Out of 15 933 patients, 10.8% were diagnosed
      with epilepsy and 175 (1.09%) patients had brain tumor, 75 (42.86%) of which were
      significantly associated with epilepsy (P > 0.05). Almost forty-three percent
      (42.86%) of tumors were epileptogenic, with no significant sex difference
      (confidence level of 95%). Fifty-seven (32.5%) brain tumor patients were aged 51
      60. The mean age of all patients with brain tumors was 41.6 years. Focal
      sensorimotor seizures were dominant in 40 (53.3%) cases. Among epilepsy cases
      with known etiology, 75 (6.8%) patients had epileptogenic tumors. Types of
      seizures in patients with epilepsy were different from seizures provoked by brain
      tumors. The most common tumor site was temporal region (43.4%). There was no
      significant difference according to epileptogenesis. Focal sensorimotor seizures
      were common in patients with frontal and parietal region tumors.

PMID- 21086730
TI  - Avoidance coping and lymphocyte count.
AB  - Stress is the key psychological activator of the hypothalamic-pituitary-adrenal
      axis and therefore an important risk factor for diminished immunocompetence. The
      aim of the study was to assess the connection between the strategies of coping
      with stress and lymphocyte counts in soldiers. Coping strategies were evaluated
      in 61 Slovenian Army members using the Coping Responses Inventory. White blood
      cell count with detailed lymphocyte analysis by use of flow cytometry was
      assessed in 33 soldiers. Factor analysis identified two factors of coping, i.e.,
      avoidance coping and approach coping. Statistically significant negative
      correlations were recorded between avoidance strategies and monocyte, lymphocyte
      and T-lymphocyte concentrations. Approach strategies, which are thought to be
      more adaptive, did not correlate with the immune system measures. These findings
      support the notion that each person's individual coping styles are reflected in
      their immune characteristics. We presume that avoidance coping might be an
      important mediating variable influencing the effects of stress on immune
      measures.

PMID- 21086731
TI  - Blindness and visual impairment in diabetic patients in Croatia.
AB  - New estimates show reduction in the number of people who are blind or suffer from
      vision impairment as a sequel of infectious diseases, while there is an increase
      in the number of people who are blind due to conditions related to longer life
      span and diabetes. Diabetic retinopathy is the leading cause of blindness in
      active population in developed countries. Epidemiological studies evaluated the
      incidence and describe many facets of this disease the incidence of which is
      being followed in most countries. The aim of this paper is to present some
      epidemiological data on diabetic retinopathy caused by type 1 diabetes in
      Croatia, to compare them with other countries, and to evaluate its importance in
      causing severe visual impairments and blindness. These data are considered highly
      relevant because they are changing constantly and require continuous monitoring
      in spite of all advances in understanding the distribution, causes and severity
      of diabetic retinopathy. It is of great importance because the increasing burden
      of diabetes will pose ever greater burden on the population at large and on
      healthcare systems providing care for these patents.

PMID- 21086733
TI  - A case of signet-ring cell carcinoma of the gallbladder: immunohistochemistry and
      differential diagnosis.
AB  - The morphological spectrum of gallbladder carcinoma is broad and variable. Most
      of these tumors are tubular adenocarcinomas. There are some tumors with unusual
      morphology that may be difficult to classify due to their rarity. One of such
      tumors is the signet-ring cell carcinoma, which is a highly aggressive, mucin
      producing variant of gallbladder adenocarcinoma predominantly or exclusively
      composed of signet-ring cells. Histologically, these tumors are similar to their
      counterparts in other organs such as stomach, colon and breast, and should not be
      misinterpreted as metastatic carcinoma from one of these primary sites. The
      literature about this variant of carcinoma is sparse and little is known about
      it. We found only three cases of signet-ring cell carcinoma of the gallbladder
      previously reported. We present the case of an 86-year-old woman with signet-ring
      cell carcinoma of the gallbladder and discuss the potential diagnostic dilemmas

PMID- 21086732
TI  - Functional outcome after thrombolytic therapy.
AB  - In this paper, we report our experience from a prospective study in 40 ischemic
      stroke patients admitted during the last two years at University Department of
      Neurology Stroke Unit, Banja Luka Clinical Center, in order to assess the safety
      and efficacy of thrombolytic therapy, the impact of age, sex and risk factors,
      and functional outcome at 6 months of intravenous tissue plasminogen activator
      treatment. According to the National Institutes of Health Stroke Scale, there
      were 5 mild, 22 moderate and 13 severe stroke cases in the study group. The
      outcome measures at 6 months of thrombolytic treatment were taken in 38 (100%)
      patients, yielding a Functional Independent Measure score > or=90 (good clinical
      outcome) in 21 (52.50%) and modified Rankin Score < or =2 (good clinical outcome)
      in 22 (55%) patients. The rate of symptomatic intracerebral hemorrhage in tissue
      plasminogen activator treated patients was 5%, with a mortality rate of 17.50%.
      The outcomes were comparable with those found in the NINDS t-PA trial. Current
      guidelines recommend a 'door-to-needle' time of less than 60 minutes and
      emphasize that 'time is brain'.

PMID- 21086734
TI  - Nontraumatic bilateral subdural hematoma caused by antiaggregation therapy: case
      report and review of the literature.
AB  - A 64-year-old female receiving clopidogrel and aspirin antiaggregation therapy
      after percutaneous coronary intervention for non-STEMI myocardial infarction
      developed nontraumatic bilateral subdural hematoma with dizziness, vertigo and
      headache. Craniotomy had to be postponed because of reduced ADP platelet
      aggregability. Four days after clopidogrel withdrawal and transfusion of 12
      platelet concentrate units, ADP aggregation transiently normalized and bilateral
      trepanation with hematoma evacuation was performed. The procedure was followed by
      excellent neurologic and clinical recovery; however, decreased platelet
      aggregability was recorded by postoperative day 12 despite strict clopidogrel and
      other platelet inhibitor withdrawal. Suspicion of Glanzmann thrombastenia was
      excluded by flow cytometry. Two weeks after neurosurgery, the right femoral vein
      thrombosis was detected by color doppler ultrasonography and therapy with
      fractionated heparin was initiated, followed by warfarin. The risk and incidence
      of hemorrhagic complications of antiaggregation and anticoagulation therapy are
      discussed. Caution is warranted on prescribing this potentially harmful therapy
      to older patients, generally burdened with other chronic comorbidities.

PMID- 21086735
TI  - Synchronous rectal adenocarcinoma and bilateral clear cell renal carcinoma.
AB  - A 69-year-old man was admitted for resection of rectal adenocarcinoma diagnosed
      by colonoscopy. Preoperative computed tomography scan and abdominal
      ultrasonography revealed bilateral renal tumors measuring up to 2 and 2.8 cm in
      largest diameter, respectively. The patient underwent partial colectomy and
      bilateral partial nephrectomy. Microscopically, rectal adenocarcinoma penetrated
      the submucosa, without invasion of the muscularis propria. Both renal tumors were
      clear cell renal carcinomas of Fuhrmann nuclear grade 2. To our knowledge, this
      is the first case of synchronous adenocarcinoma of the rectum and bilateral clear
      cell renal cell carcinoma described in the literature to date.

PMID- 21086736
TI  - Denied pregnancy.
AB  - Two cases of non-psychotic denied pregnancy are presented and discussed.
      Following obstetric expertise, the forensic-criminal evaluation should
      investigate the reported crimes of denied pregnancy associated infanticide or
      criminal abortion as well as the potential involvement of other persons in these
      crimes. All this would require close collaboration between obstetricians,
      psychiatrists and crime investigation experts in the forensic expertise of these
      criminal offences.

PMID- 21086737
TI  - An unusual case of acute urinary retention.
AB  - A 47-year-old male was referred to Emergency Department of our hospital for acute
      urinary retention. Physical examination showed electrical cable with proximal
      part introduced into the urethra. Plain abdominal radiograph demonstrated a
      metallic object in the pelvis and the patient underwent an operation. We used
      suprapubic cystostomy approach, and the wire was removed from the bladder and
      urethra.

PMID- 21086738
TI  - Creutzfeldt-Jakob disease: case report and review of the literature.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disease caused
      by an infectious protein called prion and is characterized by spongiform changes,
      neuronal loss, reactive astrocytic proliferation and accumulation of pathologic
      cellular protein, occurring in 3 general forms: sporadic or spontaneous, genetic
      or familial, and acquired form including a variant form of CJD. Clinical
      presentation of CJD is characterized by progressive dementia, neurologic symptoms
      and visual impairment, development of akinetic mutism, and eventually death,
      usually from respiratory infection. The diagnosis is based on clinical
      presentation, electroencephalogram, and typical cerebrospinal fluid and magnetic
      resonance imaging findings. A case is presented of a 56-year-old woman with
      progressive dementia, typical neurologic symptoms, positive cerebrospinal fluid
      and typical magnetic resonance imaging findings. The clinical, pathologic and
      imaging findings of this rare condition are also discussed.

PMID- 21086739
TI  - Osteochondritis dissecans of the knee in a subadult from a medieval (ninth
      century A.D.) site in Croatia.
AB  - Although osteochondritis dissecans of the knee has been known for a long time, we
      still do not fully understand why it develops. This prompted us to present and
      describe an example of osteochondritis dissecans identified in the Osteological
      Collection of the Croatian Academy of Sciences and Arts. The case of
      osteochondritis dissecans described in this report was recovered from the Gluvine
      kuce cemetery in the Dalmatian hinterland, approximately 28 km north-east of
      Split. A total of 77 graves were excavated and the individual exhibiting
      osteochondritis dissecans was recovered from grave number 16 that belongs to the
      younger phase of the cemetery that lasted during the second half of the 9th
      century A.D. Osteochondritis dissecans was noted in a subadult individual. The
      pathological changes consistent with osteochondritis dissecans are present on
      both medial femoral condyles. The lesion on the right femoral condyle is an oval
      crater-like defect with well defined margins and a porous floor of rough
      trabecular bone. The lesion on the left femoral condyle is basically, with two
      small provisions, identical to the one on the right side. The first is that it is
      slightly smaller, while the second is that unlike its antimere, it has a well
      preserved bone fragment that fits perfectly into the ostechondritic pit.
      Radiographic analyses of the femoral condyles support a diagnosis of
      osteochondritis dissecans and show a well-demarcated radiolucent defect in the
      articular surfaces of both joints surrounded by a thin sclerotic repair zone.
      According to the classification systems this degree of change corresponds to
      stage 3 or grade 3 osteochondritis dissecans--a detached but non-displaced
      fragment. Returning, for a second, to the opinion that prompted us to present
      this case, it is clear that during the last 1100 years there have been no
      significant morphological or radiological changes in the characteristics of
      osteochondritis dissecans.

PMID- 21086740
TI  - Hemoperitoneum caused by a bleeding myoma in pregnancy.
AB  - The prevalence of uterine myomas during pregnancy is estimated to range from 0.3%
      to 2.6%. Although leiomyomas usually remain asymptomatic, in one often cases they
      may be complicated. The management of uterine fibroids during pregnancy is
      largely conservative and surgical removal is generally delayed until post partum.
      A 37-year-old pregnant woman (15 weeks) with a history of gynecologic examination
      several hours before presented with lower abdominal pain and signs of acute
      abdomen. She was para-2, as she had delivered a healthy child 12 years before,
      and current pregnancy was uncomplicated until presentation. Intra-abdominal
      hemorrhage was suspected and she underwent immediate exploratory laparotomy,
      which revealed massive hemoperitoneum. A subserous uterine leiomyoma of 8.5x6.5
      cm was found in the fundus area, with an actively bleeding ruptured vessel on its
      dome. Myomectomy was successfully performed and 1.5 liter of blood and blood
      clots were evacuated from the peritoneal cavity. The histology report showed
      sections of interlacing bundles of smooth muscles with areas of bleeding and
      necrotic degeneration. The postoperative course and subsequent antenatal period
      were uneventful. The woman went into spontaneous labor at 38 weeks and delivered
      vaginally a healthy male baby. This rare case ofintra-abdominal hemorrhage due to
      bleeding myoma supports other recent studies, which have demonstrated that
      myomectomy may be successfully performed during pregnancy in selected
      circumstances.

PMID- 21086748
TI  - Effect of curcumin and ferulic acid on modulation of expression pattern of p53
      and bcl-2 proteins in 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch
      carcinogenesis.
AB  - The modulating effect of curcumin and ferulic acid was investigated on expression
      pattern of apoptosis regulatory p53 and bcl-2 proteins in oral squamous cell
      carcinoma (OSCC). The OSCC was induced in the buccal pouch of golden Syrian
      hamster by painting with 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) three-times a
      week for 14 weeks. The expression pattern of p53 and bcl-2 proteins was analyzed
      by immunohistochemical staining. We noticed 100% tumor formation in hamsters
      painted with DMBA alone for 14 weeks. Overexpression of p53 and bcl-2 proteins
      was observed in the buccal mucosa of tumor-bearing hamsters. Oral administration
      of curcumin (80 mg/kg body wt) and ferulic acid (40 mg/kg body wt) to DMBA
      painted hamsters on days alternate to DMBA painting for 14 weeks completely
      inhibited tumor formation and down-regulated the expression pattern of p53 and
      bcl-2 proteins. Our results thus demonstrated the protective role of curcumin and
      ferulic acid on DMBA-induced abnormal expression of p53 and bcl-2 proteins in the
      buccal mucosa of golden Syrian hamsters.

PMID- 21086749
TI  - Arginase isoforms in frog and lizard tissues.
AB  - Isoforms of arginase in the liver and kidney tissues of the ureotelic frog (Rana
      tigerina) and uricotelic lizard (Calotes versicolor) were fractionated by DEAE
      cellulose chromatography (pH 8.3). Four molecular forms, designated as A'1, A2,
      A3 and A4 based on the KCl concentration required for their elution from the ion
      exchange column, were detected in lizard liver, while only two forms were found
      in lizard kidney (A3 and A4) and frog liver and kidney (A2 and A3). No major
      differences were found in the pH optimum, substrate affinity and molecular weight
      of the isoenzymes. The isoforms in lizard tissues were either totally unaffected
      or only partially immunoprecipitated by antibodies raised against rat liver and
      beef liver arginases, but those in frog tissues were significantly activated by
      the two antibodies. While the physiological importance of the presence of four
      isoforms in lizard liver remains enigmatic, different sets of isoenzymes were
      present in the liver of the two ureotelic vertebrates, rat and frog. Hence, it
      appeared that a given mode of nitrotelism was not associated with a specific set
      of isoenzymes. Also, the data were not consistent with the generally held view
      that a basic isoform of arginase served as a component of the urea cycle in liver
      and a neutral/slightly acidic form functions in the synthesis of proline,
      glutamate and polyamines in extra-hepatic tissues. The isoforms appeared to show
      considerable functional overlap.

PMID- 21086750
TI  - Amelioration of alcohol-induced oxidative stress by Emblica officinalis (amla) in
      rats.
AB  - The present study was aimed at investigating the ameliorative effect of Emblica
      (Phyllanthus Emblica L) fruit extract (EFE) against alcohol-induced oxidative
      changes in plasma biochemical profile in rats. Alcohol administration (5 g/kg
      body wt/day) for 60 days resulted in significantly (P<0.05) higher levels of
      plasma nitrite/nitrate (NOx), total bilirubin, creatinine, and abnormalities in
      lipid and lipoproteins. Moreover, alcohol receiving rats showed significantly
      (P<0.05) lowered plasma total protein, albumin/globulin (A/G) ratio and uric
      acid, with no significant change in glucose level. The EFE administration (250
      mg/kg body wt/day) to alcohol-administered rats significantly modulated plasma
      lipids and lipoprotein patterns and also decreased nitrite/nitrate, total
      bilirubin and creatinine levels. EFE administration to alcohol receiving rats
      showed a significant (P<0.05) increase in plasma total protein, A/G ratio and
      uric acid levels. Total cholesterol (r = 0.466), triglycerides (r = 0.574), VLDL
      C (r = 0.578), LDL-C (r = 0.225) and total bilirubin (r = 0.419) showed a
      stronger positive correlation with that of NOx in alcohol-treated rats. The
      concentration of nitric oxide (NOx) was negatively correlated with HDL-C (r = 
      0.285) and uric acid (r = 0.392) in alcohol-treated rats. The amelioration of
      alcohol-induced oxidative stress might be due to the combined effect of
      phytophenols, such as tannins and flavonoid compounds and vitamin C.

PMID- 21086751
TI  - Protective effect of Morus rubra L. leaf extract on diet-induced atherosclerosis
      in diabetic rats.
AB  - The antiatherosclerotic effect of aqueous leaves extract of Morus rubra was
      studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath)
      diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mg
      cholesterol] for 5 consecutive days. A short-term toxicity assessment was also
      conducted in healthy rats to examine toxic effects of the extract. Oral
      administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight
      per day for a period of 30 days) produced significant (p<0.001) fall in fasting
      blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400
      mg/kg) showed significant (p<0.001) improvement in body weight and serum lipid
      profile i.e., total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol
      and VLDL-cholesterol, when compared with diabetic control. Endothelial
      dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels and oxidized LDL),
      apolipoprotein A and apolipoprotein B were significantly (p<0.001) reversed to
      near normal, following treatment with the extract. Thus, our study shows that
      aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the
      homeostasis of glucose and fat and possesses significant anti-atherosclerotic
      activity.

PMID- 21086752
TI  - Protective effect of resveratrol and vitamin E against ethanol-induced oxidative
      damage in mice: biochemical and immunological basis.
AB  - The metabolism of ethanol gives rise to the generation of excess amounts of
      reactive oxygen species and is also associated with immune dysfunction. We
      examined the efficacy of resveratrol and vitamin E on the immunomodulatory
      activity and vascular function in mice with liver abnormalities induced by
      chronic ethanol consumption by measuring the protein, liver-specific transaminase
      enzymes, antioxidant enzymes and non-enzymes such as reduced glutathione (GSH)
      content, thiobarbituric acid reactive substance (TBARS) level, nitrite level, and
      activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase
      (GR) and glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and
      cytokines such as interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor (TNF)
      alpha, gamma interferon (IFN-gamma), vascular endothelial growth factor (VEGF)-A
      and transforming growth factor (TGF)-beta1 in mice blood. Ethanol (1.6 g/kg body
      wt/day) exposure for 12 wks significantly increased TBARS and nitrite levels and
      GST activity, and significantly decreased GSH content and the activities of SOD,
      CAT, GR and GPx in whole blood hemolyzate of 8-10 wks-old male BALB/c mice
      (weighing 20-30 g). Ethanol exposure also elevated the activities of transaminase
      enzymes (AST and ALT), IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1, while
      decreasing the albumin concentration and IL-4 activity in the serum. Both
      resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) treatment
      significantly reduced AST, ALT, GST, IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF
      beta1 activities and levels of TBARS and nitrite, and elevated albumin content,
      GSH level and activities of SOD, CAT, GR and GPx, compared to ethanol-treated
      group. Thus, results from the study demonstrated that both resveratrol (5 mg kg(
      1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) can effectively ameliorate
      ethanol (1.6 g kg(-1) day(-1))-induced oxidative challenges, immunomodulatory
      activity and angiogenesis processes.

PMID- 21086753
TI  - Antioxidant levels in blood and seminal plasma and their impact on sperm
      parameters in infertile men.
AB  - Excess reactive oxygen species (ROS) beyond the scavenging capacity of
      antioxidants leads to DNA damage and oxidation of lipoprotein components at the
      cellular and subcellular level. The oxidative stress (OS) adversely affects sperm
      function by altering membrane fluidity, permeability and impairs sperm functional
      competence. In the present study, the OS status in seminal plasma and blood serum
      in infertile men and its relationship with spermatozoa parameters have been
      investigated. Four groups of infertile men viz., oligozoospermic (n = 15),
      asthenozoospermic (n = 17), teratozoospermic (n = 19), and
      oligoasthenoteratozoospermic (n = 9), and healthy fertile controls (n = 40) have
      been analyzed for superoxide dismutase (SOD), catalase (CAT), glutathione (GSH)
      and malondialdehyde (MDA) in seminal plasma and blood serum. Significant
      correlation between blood serum SOD and sperm count has been observed in patients
      (p = 0.018) and controls (p = 0.021). Similarly, significant correlation between
      blood serum GSH and sperm progressive motility in patients (p = 0.036) and
      controls (p = 0.029) is observed. The low seminal MDA is associated with increase
      in sperm progressive motility in patients (p = 0.039) and controls (p = 0.028).
      Positive correlation is found between increased seminal MDA levels and abnormal
      sperm morphology in both patients and controls (r = 0.523, p = 0.029; r = 0.612,
      p = 0.034 respectively). Correlations between blood SOD and sperm count and
      between blood GSH levels and progressive motility suggest that these can be
      important biochemical markers in assaying the sperm count and motility. A
      negative correlation of motility with seminal MDA indicates that sperm membrane
      lipid peroxidation affects the fluidity and thus mobility of sperm axoneme. This
      affects functional competence of the sperm and acts like a biological safeguard.
      The results of the present study suggest the prospects of using the blood serum
      and seminal plasma antioxidants as a valuable tool to evaluate the sperm
      reproductive capacity and functional competence.

PMID- 21086754
TI  - Effect of metformin on renal microsomal proteins, lipid peroxidation and
      antioxidant status in dexamethasone-induced type-2 diabetic mice.
AB  - An SDS-PAGE analysis of renal microsomal fraction of albino mice was performed to
      study the involvement of proteins in dexamethasone-induced type-2 diabetes
      mellitus (DM) and their alterations by metformin, a widely accepted oral
      antidiabetic drug. In addition, changes in renal lipid peroxidation (LPO),
      activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione
      (GSH) content, as well as renal somatic index (RSI) and daily rate of water
      consumption were also investigated. While dexamethasone administration (1.0 mg/kg
      for 21 days) expressed two renal proteins (43 kDa and 63.23 kDa), in addition to
      the increased fasting serum levels of glucose and insulin, renal LPO, RSI and
      daily rate of water consumption, a parallel decrease in renal SOD, CAT and GSH
      was also observed. Treatment with metformin normalized these alterations
      including the renal proteins and LPO, confirming its efficacy in ameliorating
      dexamethasone-induced type-2 DM and also the association of two proteins with
      type-2 DM.

PMID- 21086756
TI  - Isolation of 1,4-naphthalenedione, an antibacterial principle from the leaves of
      Holoptelea integrifolia and its activity against beta-lactam resistant
      Staphylococcus aureus.
AB  - Antimicrobials derived from plants have been receiving increasing attention in
      recent years. Antimicrobial activities of a number of phytochemicals have been
      reported. Many present day antibiotics are ineffective against several pathogenic
      organisms. About 90% of Staphylococcus aureus isolates from clinical specimens is
      reported to have resistance against beta-lactam antibiotics. In the present
      study, the effect of hexane, diethyl ether, acetone and water extracts of leaves
      of a medicinal plant Holoptelea integrifolia has been tested against beta-lactam
      resistant strain of S. aureus in presence of antibiotics such as ampicillin,
      amoxicillin, cefotaxime and ceftriaxone. The diethyl ether extract has shown the
      maximum antibacterial activity and the active principle is found to be 1,4
      naphthalenedione which is characterized by GC-MS and FTIR spectroscopy. The
      minimum inhibitory concentration (MIC) of the compound is found to be 4 mg/ml.
      Structural similarity of this compound with a functional group of a beta
      lactamase-resistant antibiotic indicates that 1,4-naphthlenedione may be acting
      as an inhibitor to beta-lactamase.

PMID- 21086755
TI  - In vitro antioxidant activity of Hedyotis corymbosa (L.) Lam. aerial parts.
AB  - The methanolic extract of the aerial part of Hedyotis corymbosa (L.) Lam.
      (Rubiaceae) was screened for antioxidant activity using 1,1-diphenyl-2-picryl
      hydroxyl (DPPH) quenching assay, 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic
      acid (ABTS) cation decolorization test, ferric reducing power (FRP), scavenging
      capacity towards hydroxyl ion (OH*) radicals and nitric oxide (NO) radical
      inhibition activity using established assay procedures. Total phenolics and total
      flavonoid contents were, also determined. The plant yielded 210 mg gallic acid
      equivalent/100 g phenolic content and 55 mg quercetin equivalent/100 g flavonoid
      content. The extract exhibited high antiradical activity against DPPH, ABTS,
      nitric oxide and hydroxyl radicals with EC50 value of 82, 150, 130, and 170
      microg/ml, respectively. The FRP increased with increasing concentration of the
      sample. The antioxidant activity of the extract was comparable with that of the
      standard butylated hydroxyl toluene (BHT). High correlation between total
      phenolic/flavonoid contents and scavenging potential of different reactive oxygen
      species (R2 = 0.785-0.998) indicated the polyphenols as the main antioxidants.

PMID- 21086757
TI  - Preparation and characterization of biopolymeric nanoparticles used in drug
      delivery.
AB  - Nanotechnology plays an important role in advanced biology and medicine research
      particularly in the development of potential site-specific delivery systems with
      lower drug toxicity and greater efficiency. These include microcapsules,
      liposomes, polymeric microspheres, microemulsions, polymer micelles, hydrogels,
      solid nanoparticles etc. In the present study, preparation and characterization
      of biopolymeric gelatin nanoparticles for encapsulating the antimicrobial drug
      sulfadiazine and its in vivo drug release in phosphate buffer saline (PBS) have
      been investigated. The nanoparticles prepared by second desolvation process
      varied in a size range 200 nm and 600 nm with a drug entrapment efficiency of 50%
      characterized by atomic force microscopy and dynamic light scattering. The drug
      release from the nanoparticles occurred up to 30% in a controlled manner.

PMID- 21086758
TI  - Age-related progressive synaptic dysfunction: the critical role of presenilin 1.
AB  - Mutations in presenilin 1 gene (PS1) account for the majority of early-onset
      familial Alzheimer's disease (FAD) cases. The disease is characterized by
      intracellular neurofibrillary tangles and extracellular amyloid fibrils composed
      of amyloid beta peptides (Abeta). Two successive cleavages are necessary to free
      the Abeta peptide from the amyloid precursor protein (APP). Gamma-secretase
      catalyzes the final cleavage of APP to generate Abeta peptides. PS1 is a
      catalytic subunit of gamma-secretase and is also involved in the cleavage of many
      membrane proteins. PS1 also has functional interactions with many other proteins.
      The use of animal models of AD has initiated the deciphering of these molecular
      pathways and mechanisms. Transgenic mouse models are useful to study the features
      of FAD and to investigate the nature of the neural-tissue changes of the disease
      and their evolution during aging. When expressed alone, mutations in human PS1 do
      not induce any detectable lesions, although they do increase Abeta peptides. This
      absence has led to the criticism that PS1 mouse models are not valuable for the
      study of AD. In this review we present how studies using PS1 transgenic mice have
      raised new questions related to pathological mechanisms of AD and are useful
      models for the study of (1) progressive cognitive decline, (2) early-occurring
      synaptic dysfunction, and (3) mechanisms other than amyloidogenesis that can be
      involved in disease pathogenesis.

PMID- 21086759
TI  - Pathogenic TARDBP mutations in amyotrophic lateral sclerosis and frontotemporal
      dementia: disease-associated pathways.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are late
      onset neurodegenerative disorders that are associated with mutations in the
      TARDBP gene. The product of this gene, TDP-43, has also been identified as the
      main component of the intracellular inclusions typical of most cases of ALS and
      FTD. Recent evidence suggests that TDP-43 is essential for proper development and
      involved in several fundamental cellular processes, including gene transcription,
      RNA processing, and the spatial regulation of mRNA translation. Pathogenic TARDBP
      mutations that impair TDP-43 function could therefore be related to neuronal
      degeneration in ALS and FTD. Conversely, cellular and animal studies have shown
      that pathogenic TARDBP mutations induce neuronal toxicity through mislocalization
      or elevated concentrations of TDP-43, consistent with a gain-of-function
      mechanism. In this review, we focus on the physiologic functions of TDP-43 within
      the central nervous system and discuss how these functions may be perturbed or
      pathologically altered by disease-associated mutations.

PMID- 21086760
TI  - Antibody therapy in neurodegenerative disease.
AB  - Advances in medical science have led to increased life expectancy and increased
      median age in the population. Because the symptoms of neurodegenerative diseases
      generally onset in mid- to late-life, a concomitant increase in the number of
      persons afflicted with these devastating diseases has occurred. Developing
      therapies for neurodegenerative diseases is of the highest priority due to the
      enormous cost of medical care required, as well as for the human suffering
      involved. Although caused by a variety of genetic and environmental insults, such
      diseases share commonalities. Many of these diseases are proteinopathies-
      diseases caused by misfolded, aggregating proteins. Antibodies that can recognize
      and remove misfolded proteins are ideally suited for proteinopathy therapeutics.
      The numerous intriguing advances in antibody-based therapies for
      neurodegenerative diseases are discussed in this review.

PMID- 21086761
TI  - Dopaminergic impact on cortical excitability in humans.
AB  - Dopamine is a major neuromodulatory agent of the central nervous system. The
      neurotransmitter has a non-linear dose-dependent effect on cortical excitability
      and activity, which depends on spontaneous activity, dopamine concentration, and
      dopaminergic sub-receptors, amongst others. By its impact on cortical and
      subcortical network activity and excitability, dopamine modulates such cognitive
      performance as attention, as well as learning and memory formation. Although
      animal studies have enhanced our knowledge about the physiology of dopamine
      considerably, the transferability of the results to conscious humans is limited
      due to altered spontaneous neuronal activity in anesthetized animals or slice
      experiments. Recently emerged noninvasive brain stimulation techniques enable the
      exploration of cortical excitability in humans. Here we review the respective
      experimental results and derive conclusions about how dopamine might affect the
      cortical excitability of the human brain.

PMID- 21086762
TI  - NF-kappaB signaling in neurite growth and neuronal survival.
AB  - The nuclear factor kappa B (NF-kappaB) transcription factor system plays multiple
      roles in the function of the nervous system during development and postnatal
      physiology. In the developing nervous system, neurite outgrowth could be
      regulated by both canonical and alternative NF-kappaB signaling pathways. The
      degree and site of NF-kappaB activation could promote or inhibit neuronal
      survival in a complex, signal and subunit-dependent manner. The significance and
      mechanistic basis of some of NF-kappaB activity in neurons have remained
      controversial. We discuss our current understanding and recent findings with
      regard to the roles of NF-kappaB in the neurite outgrowth and neuronal survival,
      and how NF-kappaB activation is associated with the pathophysiology of ischemic/
      traumatic injuries and neurodegenerative diseases.

PMID- 21086763
TI  - SORLA/SORL1, a neuronal sorting receptor implicated in Alzheimer's disease.
AB  - The proteolytic breakdown of the amyloid precursor protein (APP) to neurotoxic
      amyloid-beta peptides in the brain has been recognized as a major pathological
      pathway in Alzheimer's disease (AD). Yet, the factors that control the processing
      of APP and their potential contribution to the common sporadic form of AD remain
      poorly understood. Here, we review recent findings from studies in patients and
      in animal models that led to the identification of a unique sorting receptor for
      APP in neurons, designated SORLA/SORL1, that emerges as a key player in
      amyloidogenic processing and as major genetic risk factor for AD.

PMID- 21086764
TI  - Ten years development of human resources in Serbian health system.
AB  - A key component of any healthcare reform process is to ensure that the services
      are delivered by the right numbers of staff with appropriate skills and training.
      In 2007, public health institutions in Serbia had 2% more employees than before
      the economic transition. Nevertheless, the trend of the total number of employees
      in the Serbian health care system still preserved a mild rising trend. The most
      prominent changes in the structure of human resources were effectuated in the
      total numbers of physicians, nurses and administrative and technical staff.
      Development of medical science and practice in Serbia is characterized by more
      intensive processes of specializations, resulting in increased number of
      specialists among medical doctors. Health care provided in in-patient
      institutions still employs most of the doctors. The number of unemployed
      physicians, dentists and pharmacists has been rising since 2000. Another aspect
      that explains the rise of unemployed, university educated human resources is the
      rising number of graduated physicians, dentist and pharmacists. Health care
      policy makers may recognize the need for more integrated planning of human
      resources in health care, in particular, making management of human resources
      responsive to system needs and design, instead of vice versa.

PMID- 21086765
TI  - Implementation of the action plan for human resources in the health system of
      Serbia--facing inherited problems.
AB  - It is through an objective insight into the situation of the health system, in
      the period of a ten-year isolation of the country, that the policy of planning
      staff has been defined. The Ministry of Health of the Republic of Serbia has
      produced an Action Plan for Human Resources for 2005-2010, after having performed
      the analysis of the situation. It is based on the evaluation of the health status
      of the inhabitants and its internal migrations. The Action Plan is focused on the
      efforts to meet international standards with respect to the building of human
      resources in the health sector. The consistent implementation of defined norms is
      an important issue for further development of the health system and the
      maintenance of its sustainability.

PMID- 21086766
TI  - Human resources data collection--Central Information Service.
AB  - The Central Information Service--(CIS) is located at the Institute of Public
      Health of Serbia, which maintains and upgrades it. CIS has been developed through
      the Serbia Health Project, a project developed by the Ministry of Health and
      funded by the World Bank loan. Through its web portal CIS ensures that all health
      institutions enter and maintain HR and other resource data, at the same time
      enabling all users of the system (Ministry of Health, Health Insurance Fund,
      Institutions of Public Health, all health institutions) to use CIS data in
      accordance with the pre-established rights. In the following period CIS will
      offer its services to the private sector as well, and it shall be a basis for the
      establishment of Serbia e-Health portal for citizens.

PMID- 21086767
TI  - An approach to assess trends of pharmacist workforce production and density rate
      in Serbia.
AB  - The policy dialog on human resource in health care is one of the central issues
      of the ongoing health care system reform in the Republic of Serbia. Pharmacists
      are the third largest health care professional group, after nurses and doctors.
      This study's objective was to analyze population coverage with pharmacists
      employed in the public sector of health care system of Serbia during 1961 - 2007,
      and to project their density by 2017. In this respect, additionally, time-series
      of annual number of enrolled and graduate pharmacy students were modelled. Time
      trends of routinely collected national statistical data, concerning the
      pharmacists, were analyzed by join point regression program, according to grid
      search method. During the observed period of time, in Serbia, pharmacist
      workforce production and deployment trends were generally positive, but with
      different annual dynamic. Key findings were the slow rise of pharmacist workforce
      density rates per 100,000 population; the insufficient balance between
      pharmacists workforce supply side (annual number of enrolled and graduated
      students) and the public health care sector's ability to absorb annual number of
      pharmacy graduates. For ten years ahead, density rates of publicly active
      pharmacist workforce would probably increase for 46%, if no policy interventions
      were planned to adverse trends of pharmacist workforce production and deployment
      in public health care sector. The study results may be useful for variety of
      stakeholders to better understand how and why the supply and deployment of
      pharmacists were changing; and that the coordination among policy interventions
      is a crucial successes factor for a health workforce development plan
      implementation. The repercussions of any changes made to the pharmacy workforce,
      need to be considered carefully in advance.

PMID- 21086768
TI  - Job satisfaction among health care workers in Serbia.
AB  - According to literature review there seems to be a general agreement that job
      satisfaction among doctors is declining. This study's objective was to identify
      job satisfaction levels and their causes among health care workers, employed at
      the public health institutions. A job satisfaction survey of health care workers
      was therefore carried out in 197 public health centers in the Republic of Serbia,
      157 primary health care centers and 40 general hospitals, in 2008. A satisfaction
      questionnaire, containing 24 items was used to investigate job satisfaction.
      Respondents (23.259), working in primary health care, indicated an average job
      satisfaction level of 3.08 +/- 0.67 on a 5-point scale. Respondents (11.302),
      working in general hospitals, indicated a lower average job satisfaction level of
      2.96 +/- 0.63. The reported level of satisfaction was the highest for their
      opportunities to use their abilities, cooperation with colleagues and fellow
      workers, and freedom to choose their own methods of work. Doctors, working in
      primary health care centers, reported higher level of job satisfaction than
      hospital doctors. Overall, job satisfaction of doctors and nurses is relatively
      low. Increased pay rate and more adequate equipment, as well as possibilities for
      education and career improvement, would enhance their job satisfaction.

PMID- 21086769
TI  - Health care managers as a crucial component of health care workforce in Serbia.
AB  - The aim of the paper was to describe and analyse health services management in
      Serbia, commencing with present status and projecting, as accurately as possible,
      future changes over the next years, skills and required competencies of the
      health management workforce. The study was done as a part of Ministry of
      Health/EU funded Project "Preparation for Health Management Training Programme in
      Serbia" by a desk review of current and draft legislation, related projects in
      the health sector and relevant local and international literature; semi
      structured interviews with key local and international stakeholders and a
      structural analysis of the health management sector. The results of the study
      have shown that there was a big gap in knowledge and skills regarding Health
      Management in Serbia and a true need for such type of education.

PMID- 21086770
TI  - Smoking habits of employees in public-health institutes.
AB  - This study's aim is to gain the insight on smoking prevalence at the Institutes
      of Public Health in Serbia. METHOD: All Institutes of Public Health in Serbia
      have participated in the study. All employees have participated in an
      epidemiology survey, which is used to collect data. RESULTS: The questionnaire on
      smoking was completed by 83,2% (2458) of employees in the public-health
      institutes and institutions in the Republic of Serbia. The questionnaire was
      filled in by 27,1% males, and 72,95% females, in other words, the gender ratio
      was 1:2,7 respectively, which corresponds to gender ratio of the total number of
      employees in these institutes and institutions. Smoking prevalence among the
      employees according to the Occupation: Of the total number of questioned
      employees in Serbian public-health institutes and institutions 1078 are smokers
      (43,8%). Smoking habits among the employees according to occupation are as
      follows: Physician smokers 31.1% (134), Secondary-school medical staff smokers
      48.1% (507), and non-medical staff smokers 45.0% (437). CONCLUSION: Even though
      medical personnel hold a key-role in smoking prevention and quitting smoking,
      smoking among them is at a high rate. Taking into consideration that institutes
      and institutions of public health have a promotional anti tobacco and prevention
      role, the first step in carrying out the National strategy of tobacco control
      should be the appliance of the Codex of behavior of medical personnel in tobacco
      control, and the decrease in the number of smokers among the employees in health
      institutes.

PMID- 21086771
TI  - Continuous medical education (CME) of general practitioners (GP) in primary
      health care settings in the field of identification and diagnosis of alcoholism.
AB  - Institute of Public Health of Serbia (IPHS) is developing new function related to
      better monitoring of alcohol related diseases and injuries, actions focusing on
      alcohol as a lifestyle related factor using integrated strategic approaches for
      both population and individual risk reduction. In that regard the long term
      objective of the IPHS is to study, monitor, promote and safeguard public health-
      from the point of view of mental health and alcohol abuse--by means of research,
      development and the provision of expert services. Starting point in the
      aforementioned need for the capacity building in the area of mental health and
      alcohol abuse is the Program of education of general practitioners (GPs) in
      primary health care settings for identification and diagnosis of alcoholism. This
      is because GPs have the widest contact with the general population. Their
      education related to recognition of alcohol abuse and appropriate diagnostic
      tools application is first, but very important step in providing direction of the
      health service and other sectors for problem solving and would bring the largest
      benefit for the whole population. In the year 2010 National program against
      alcohol abuse and alcoholism will be developed. Program of education of GPs is
      very important complementary activity which outcome will have great impact on the
      National program implementation.

PMID- 21086773
TI  - Mental health research and practice: current challenges and opportunities for
      nursing.

PMID- 21086772
TI  - Lynn McDonald: champion of Florence Nightingale.

PMID- 21086774
TI  - The next steps in the promotion and protection of positive mental health.

PMID- 21086775
TI  - Mental health challenges and strengths of street-involved youth: the need for a
      multi-determined approach.
AB  - The social environments and activities of homeless youth frequently create a
      downward spiral, leading to drug abuse and survival sex as well as self-harm
      behaviours and suicidality. This study employed a mixed-methods approach to
      assess the mental health challenges and strengths of street-involved youth. A
      convenience sample of 70 homeless young people completed a series of standardized
      questionnaires evaluating mental health symptoms as well as resilience and self
      esteem. Two focus groups were also held to capture the perceived mental health
      needs of street-involved youth. These young people (aged 16-24) were found to
      have high levels of mental health symptoms compared to other groups of young
      adults. However, they also exhibited moderately high levels of resilience and
      self-esteem. Therefore, multi-component mental health programs and interventions
      that address both strengths and challenges may well help street-involved youth to
      work towards social re-integration and, ultimately, improved quality of life.

PMID- 21086776
TI  - Addressing the determinants of child mental health: intersectionality as a guide
      to primary health care renewal.
AB  - Primary health care (PHC) renewal was designed explicitly to attend to the
      multidimensional factors impacting on health, including the social determinants
      of health. These determinants are central considerations in the development of
      integrated, cross-sectoral, and multi-jurisdictional policies such as those that
      inform models of shared mental health care for children. However, there are
      complex theoretical challenges in translating these multidimensional issues into
      policy. One of these is the rarely discussed interrelationships among the social
      determinants of health and identities such as race, gender, age, sexuality, and
      social class within the added confluence of geographic contexts. An
      intersectionality lens is used to examine the complex interrelationships among
      the factors affecting child mental health and the associated policy challenges
      surrounding PHC renewal. The authors argue that an understanding of the
      intersections of social determinants of health, identity, and geography is
      pivotal in guiding policy-makers as they address child mental health inequities
      using a PHC renewal agenda.

PMID- 21086777
TI  - Depression in nurses.
AB  - Patient outcomes are reliant on nursing calibre, which in turn is dependent on
      the health of work environments and practice settings. The National Survey of the
      Work and Health of Nurses (NSWHN) examined a broad spectrum of nurses' work and
      health, with one finding of particular concern: Nurses have a higher rate of
      depression (1 in 10) than their counterparts (as found in other national
      surveys). This secondary analysis of the data focused on the outcome of
      depression in a subsample of the nurses surveyed by the NSWHN and examined
      associations between depression and work-related variables such as job strain,
      role overload, respect, social and employer supports, and nurses' perception of
      the quality of the care they provided. A multivariate logistic regression found
      an increased risk of depression in nurses experiencing job strain, role overload,
      and a lack of respect.

PMID- 21086778
TI  - Mental health differences among middle-aged sawmill workers in rural compared to
      urban British Columbia.
AB  - The study sought to determine whether differences in mental health outcomes were
      observable in a cohort of workers living in rural compared to urban places in the
      Canadian province of British Columbia. The study was based on a cohort of male
      sawmill workers. The cohort was probabilistically linked to the BC Linked Health
      Database in order to yield objective mental health outcomes. A nested case
      control design was used. Univariate and multivariate models were constructed
      using conditional logistic regression. While results differed according to the
      particular mental health outcome, after controlling for socio-economic
      confounders it was found that workers who remained in or migrated to rural places
      tended to have better mental health outcomes than workers who remained in or
      migrated to urban places.

PMID- 21086779
TI  - The Mental Health Commission of Canada is three years old: an update and
      reflection.

PMID- 21086781
TI  - Addressing physical health problems experienced by people with schizophrenia in
      Canada: a critical literature review.
AB  - The authors present a critical review of the literature produced by Canadian
      researchers regarding medical co-morbidities and the resources and strategies
      they recommend for assessing and managing the physical health problems of people
      with schizophrenia. Scientific production in the field consists of 9 original
      research articles and 6 literature reviews, revealing a dearth of studies in this
      area in Canada. The studies examined show that diabetes, obesity, heart disease,
      and substance abuse are the most frequent co-morbidities affecting people with
      schizophrenia. Another finding is that most researchers are challenged
      methodologically to generalize results due to limitations in design or sample
      characteristics. The authors point to the need for more research to better
      understand the role of treatment, individual characteristics, lifestyle, and
      structural issues in the development of co-morbidities among people with
      schizophrenia. They also discuss the importance of addressing these topics in
      nursing practice and education.

PMID- 21086780
TI  - Uptake of critical knowledge in nursing practice: lessons learned from a
      knowledge translation study.
AB  - This article is based on a knowledge translation (KT) study of the transition of
      patients from hospital to home. It focuses on the lessons learned about the
      challenges of translating research-derived critical knowledge in practice
      settings. The authors situate the article in current discourses about KT; discuss
      their understanding of the nature of critical knowledge; and present themes from
      their body of research, which comprises the knowledge that was translated. The
      findings have the potential to guide future KT research that focuses on the
      uptake of critical knowledge in nursing practice.

PMID- 21086782
TI  - Concentrations of sRAGE in serum and follicular fluid in assisted reproductive
      cycles--a preliminary study.
AB  - BACKGROUND: To investigate inflammatory processes during ovarian
      hyperstimulation, we have studied the soluble receptor for advanced glycation end
      products (sRAGE) levels in sera and follicular fluids of women undergoing in
      vitro fertilisation (IVF) cycle. METHODS: A total of thirty-three women
      undergoing IVF treatment were recruited, the number of follicles in investigated
      IVF cycles was 18 +/- 10 (mean +/- SD), oocytes 12 +/- 8, and the clinical
      pregnancy rate was 42% (14/33). The control group of serum samples was comprised
      of 35 healthy female blood donors. Sera and follicular fluids were examined for
      sRAGE levels by enzyme-linked immunosorbent assay (sRAGE ELISA, Quantikine, R&D
      Systems). RESULTS: Serum levels of sRAGE in women after ovarian hyperstimulation
      and induction of ovulation (1039 +/- 493 pg/mL) were significantly lower than in
      healthy blood donors (1535 +/- 438 pg/mL), p = 0.045. Follicular sRAGE levels
      (4355 +/- 1100 pg/mL) were significantly higher than serum levels (1039 +/- 493
      pg/ml), p < 0.001. Serum sRAGE levels showed significant negative correlation
      with the number of stimulated follicles (r = -0.71, p = 0.01) and retrieved
      oocytes (r = -0.54, p = 0.048). Women who successfully conceived after the IVF
      showed significantly higher sRAGE levels in follicular fluid (4595 +/- 925 pg/mL)
      compared to women who did not conceive (3986 +/- 806 pg/mL), p = 0.031.
      CONCLUSIONS: Concentration of sRAGE in follicular fluid is several-fold higher
      compared to serum and most other biological fluids investigated until this time.
      It supports the hypothesis that mammalian ovulation can be compared to an
      inflammatory event. A significant negative correlation of serum sRAGE with the
      yield of follicles and oocytes, together with the high follicular sRAGE levels,
      in particular in women who conceive after the IVF, could be explained by the
      essential outflow of sRAGE to the follicular compartment.

PMID- 21086783
TI  - Evaluation of a new monoclonal anti-k (anti-KEL2) reagent.
AB  - BACKGROUND: The first monoclonal anti-k (anti-KEL2) reagent of the IgM-class
      (clone: LK1) for the tube spin method is now commercially available. As this
      reagent is directly agglutinating in contrast to conventional polyclonal anti-k
      reagents requiring an indirect antiglobulin test, we studied the reaction
      characteristics of this new reagent carefully before starting its use in our
      routine blood grouping laboratory. METHODS: The titer of the monoclonal anti-k
      reagent (manufacturer: Biotest, D-63303 Dreieich) was compared with that of two
      polyclonal anti-k reagents. The avidity was tested with 2 K+k+ red blood cells
      (RBCs). The reactivity was examined by 10 K+k+ and 3 K-k+ blood samples.
      Specificity was tested with 12 k- RBCs from several antibody identification
      panels and from well known blood donors. The influence of a positive direct
      antiglobulin test was examined by using antibody-loaded RBCs. RESULTS: The titer
      of the monoclonal reagent was the same as that of one of the polyclonal reagents
      and one geometrical titer step lower than that of the other. At immediate spin
      and after 5, 10 and 15 minutes incubation at room temperature the reactions of
      the monoclonal reagent were clear. All 10 K+k+ and all 3 K-k+ blood samples were
      detected. No false positive reactions were found with RBCs carrying the most
      important antigens of the ABO, Lewis, P, Rhesus, Kell, Duffy, Kidd, Lutheran,
      Colton, and Cartwright system. After loading k- D+ RBCs with an incomplete anti-D
      no false positive reactions were seen. Loading K-k+ RBCs with incomplete anti-k
      also had no significant influence on the reaction. CONCLUSIONS: Several general
      advantages of monoclonal reagents of the IgM-class were seen in the new
      monoclonal anti-k as well: direct agglutination without an indirect antiglobulin
      test; rapid and simple performance; use in a saline milieu also allowing the
      examination of RBCs with a positive direct antiglobulin test; lack of false
      positive reactions caused by contaminating antibodies in the reagent. As in
      Germany two different reagents must be used for testing a RBC antigen, a further
      anti-k reagent with a different monoclonal antibody of the IgM-class would be a
      useful addition.

PMID- 21086784
TI  - Stability of red blood cell folate in whole blood and haemolysate.
AB  - BACKGROUND: Folate, a water soluble B vitamin, is necessary for normal cell
      growth and DNA synthesis. A deficiency leads to megaloblastic anaemia and
      possible neurological sequelae. Since we receive samples from distant clinics and
      experience problems due to the long transit times to our laboratory, we carried
      out a folate stability study. METHODS: Fasting blood samples were drawn from 40
      healthy volunteers. We determined the baseline red blood cell (RBC) folate in
      duplicate on each sample. Half the sample was then stored at various temperatures
      prior to haemolysate formation and RBC folate was determined regularly to
      determine sample stability. The other half was haemolysed, the haemolysate stored
      at various temperatures and analysed regularly to determine haemolysate
      stability. A statistical test of equivalence was applied using 18% as a pre
      defined limit. RESULTS: We found that whole blood was stable at 4 degrees C up to
      72 hours. At room temperature stability has been proven up to 24 hours. Results
      of additional experiments with haemolysate support stability under all conditions
      for 12 hours. CONCLUSIONS: Samples for RBC folate determination transported from
      distant clinics are stable for up to 72 hours at 4 degrees C or at room
      temperature for at least 24 hours. The prepared haemolysates may be stored at -20
      degrees C. Our experiments show that sample transportation at higher temperature
      does not affect folate stability within our predefined limits.

PMID- 21086785
TI  - Assessment of cellular and plasma oxidative stress in SAHS patients before and
      after continuous positive airway pressure treatment.
AB  - BACKGROUND: Several indirect techniques have been used for measuring oxidative
      stress in sleep apnoea-hypopnoea syndrome (SAHS) patients. The purpose of this
      study was to find out if both, cellular or plasma oxidative stress evaluations,
      are good estimators to assess oxidative stress in SAHS patients before and after
      one month's CPAP treatment. METHODS: The study included 28 SAHS patients
      requiring CPAP treatment and 15 healthy control subjects. Plasma and serum
      oxidative stress biomarkers (lipid peroxidation, total antioxidant capacity, and
      the activities of glutathione peroxidase, glutathione reductase, glutathione s
      transferase, catalase and superoxide dismutase) were measured using commercial
      kits. Cellular oxidative stress biomarkers (mitochondrial membrane potential,
      intracellular glutathione, superoxide anion, and hydrogen peroxide) were analysed
      by flow cytometry. The Wilcoxon test for paired samples was used to compare
      oxidative stress and clinical parameters in patients before and after treatment
      with CPAP. Relationships in oxidative stress markers between controls and
      patients were analyzed using the Mann-Whitney U test. The Spearman correlation
      coefficient was calculated to estimate the linear correlations between variables.
      RESULTS: Oxidative stress was notably decreased after CPAP. Before CPAP, SAHS
      severity positively correlated with hydrogen peroxide levels, while negative
      correlations were observed between SAHS severity and plasma TAC in patients.
      Also, plasma glutathione peroxidase activity negatively correlated with cellular
      superoxide anion, while plasma superoxide dismutase activity positively
      correlated with intracellular glutathione. After CPAP, plasma TAC and glutathione
      peroxidase activity negatively correlated with cellular hydrogen peroxide and
      superoxide anion. CONCLUSIONS: In conclusion, this study seems to confirm that
      plasma and cellular assessment reflect, in the same way, the oxidative stress
      status of the studied patients. Furthermore, plasma total antioxidant capacity as
      well as cellular hydrogen peroxide levels can be good markers for assessing
      oxidative stress in SAHS patients.

PMID- 21086786
TI  - The relationship between methylation of the Syk gene in the promoter region and
      the genesis of lung cancer.
AB  - BACKGROUND: To study the expression of the Syk (Spleen Tyrosine Kinase) gene and
      methylation in its promoter region in lung cancer. To investigate the
      relationship between silencing of the Syk gene and DNA methylation of the Syk
      promoter region. METHODS: RT-PCR (Semi-quantitative reverse transcription PCR),
      Real-time PCR (Real-time quantitative PCR) and immunohistochemistry technique,
      the expression of Syk in specimens from 3 lung cancer cell lines and 16 lung
      cancer patients (tumor tissues and adjacent normal tissues). MSP (Methylation
      specific PCR) was used to analyze the methylation status of the Syk promoter
      region. Then we also investigated the role of restoring Syk expression by using a
      DNA methyltransferase inhibitor, 5-aza-CdR (5-aza-2'-deoxycytidine), in
      suppressing invasion of lung cell lines. RESULTS: No expression of the Syk gene
      was detected in the 3 lung cancer cell lines. In the 16 lung patient samples, Syk
      expression was significantly lower in the tumor tissues than in the adjacent
      normal tissues (P < 0.05). Consistently, immunohistochemistry analyses of Syk
      protein expression showed that in the cancer tissues Syk protein expression
      accounted for 5% (1/20), and in the adjacent normal tissues the rate of
      expression was 100% (20/20). The correlation was highly significant (chi2 =
      36.19, P < 0.005). In the only case that showed a positive expression of cancer
      textus, the level was inferior to the adjacent tissue. In the two lung cancer
      cell lines (L9981, A549) that lack the endogenous Syk epression, 4uM
      demethylation agent 5-aza-CdR treatment was able to reactivate the Syk gene
      expression. CONCLUSIONS: Hypermethylation leads to silencing of the Syk gene in
      human lung carcinoma. Methylation of the Syk promoter and loss of Syk expression
      in lung cancer are independent biomarkers, a determination which may offer
      guidance for selecting appropriate diagnoses and treatments. Syk may be a
      potential tumor suppressor in human lung cancer.

PMID- 21086787
TI  - An approach to establish reference intervals for thyrotropin in pregnancy using
      the ADVIA Centaur analyzer.
AB  - BACKGROUND: Reference values for thyrotropin (TSH) from weeks 5 to 17 of
      pregnancy in women living in a moderately iodine-deficient area in Italy have
      never been calculated using the Advia Centaur analyzer. METHODS: TSH was measured
      in surplus blood samples drawn from 657 pregnant women: 101 in weeks 5-6 (group
      I), 333 in weeks 7-8 (group II), 139 in weeks 9-10 (group III), 44 in weeks 11-12
      (group IV), and 40 in weeks 13-17 (group V) of pregnancy. Health-Related Limits
      (HRLs) were calculated with GraphROC software using the indirect Kairisto's
      procedure and the "robust method" advocated by the CLSI C28-A3 Guideline.
      RESULTS: The HRLs of TSH concentration (indirect method) were 0.36 - 3.78 mU/L in
      group I, 0.19 - 3.07 mU/L in group II, 0.23 - 2.90 mU/L in group III, 0.13 - 3.28
      mU/L in group IV, and 0.45 - 3.90 mU/L in group V. The Upper Reference Limit
      calculated using the robust method decreased in group II-IV and increased in
      group V. CONCLUSIONS: TSH concentration decreases in the second half of the first
      trimester of pregnancy and increases in the second trimester. The indirect method
      is reliable for calculating HRLs for TSH in pregnancy, as confirmed by the robust
      method. The TSH concentrations in group I were statistically different from those
      of groups II, III, and IV, but not of those of group V.

PMID- 21086788
TI  - Potassium, calcium, magnesium, and sodium levels in biological samples of
      Pakistani myocardial infarction patients at different stages as related to
      controls.
AB  - BACKGROUND: Many studies have examined the association between cardiovascular
      disease (CVD) mortality and the intake of essential micronutrients (potassium
      (K+), calcium (Ca(2+)), magnesium (Mg(2+)), and sodium (Na+)). They may
      separately reduce the CVD incidence to a small degree over the short term levels.
      The aim of the present study was to compare the levels of micronutrients in
      biological samples (whole blood, urine, and scalp hair) of myocardial infarction
      (MI) patients of both genders where ages ranged from 45 to 60 years at first,
      second and third heart attack (n = 232). For comparison purposes, healthy age
      matched referent subjects (n = 103) and patients with cardiovascular without MI,
      of both genders were also selected. METHODS: The elemental concentrations in
      scalp hair and whole blood were measured by flame atomic absorption
      spectrophotometer prior to microwave-induced acid digestion. The validity and
      accuracy was checked by means of certified reference materials. RESULTS: The
      results of this study showed that the mean values of K+ and Mg(2+) were
      significantly reduced, while the Na+ level was higher in blood and scalp hair
      samples of MI patients as com-pared to control subjects of both genders (p <
      0.05). The levels of Ca(2+) in the biological samples of MI patients were found
      to be higher than in referents, but the difference was not significant (p >
      0.05). The urinary levels of these elements were found to be higher in MI
      patients than in the age-matched healthy controls. CONCLUSIONS: Although these
      data do not prove a causal relationship, these results are consistent with the
      hypothesis that deficiency and efficiency of some essential micronutrients may
      play a role in the development of heart disease. The micronutrient supplements
      containing K+ and Mg(2+) may be beneficial, but because of potential risks, use
      should be carefully monitored and restricted to men taking potassium-losing
      diuretics.

PMID- 21086789
TI  - Carbonyl proteins as a clinical marker in Alzheimer's disease and its relation to
      tryptophan degradation and immune activation.
AB  - BACKGROUND: The question arises whether oxidative stress is connected with
      systemic immune activation in Alzheimer's disease (AD) and mild cognitive
      impairment (MCI). During immune response interferon-gamma stimulates the
      kynurenine (Kyn) pathway, a major route of L-tryptophan (Trp) degradation.
      METHODS: Plasma Kyn, Trp and the Kyn to Trp ratio (Kyn/Trp), carbonyl proteins
      (CP) as oxidative stress parameter and homocysteine, neopterin, folate and
      vitamin B12 were measured from patients with AD and MCI (n = 16: 6 females and 4
      males with AD, 3 females and 3 males with MCI; 63.3 +/- 13.7 years), and an age
      matched healthy control group (n = 15: 11 females and 4 males; 62.8 +/- 3.6
      years). We correlated the oxidative stress parameter CP with the degradation of
      Trp creating a new quotient CP/Trp and calculated the sensitivity, specificity,
      and cut-off values for CP, Trp, CP/Trp, and Kyn/Trp using discriminate analysis.
      RESULTS: CP was significantly higher in AD/MCI (930 +/- 265 pmol/mg; p < 0.001)
      compared to controls (300 +/- 120 pmol/mg), Trp was significantly lower in AD/MCI
      (48.9 +/- 9.0 micromol/L; p < 0.001) than controls (65.2 +/- 10.7 micromol/L).
      While Kyn showed no significant difference between AD/MCI (1.72 +/- 0.56
      micromol/L) and controls (1.53 +/- 0.29 micromol/L), Kyn/Trp was significantly
      higher in AD/MCI (35.2 +/- 8.8 micromol/mmol; p < 0.001) than in controls (23.7
      +/- 4.2 micromol/mmol). CP/Trp ratio was more than 4 fold higher in the AD/MCI
      group (19.8 +/- 7.76 [(pmol/mg)/(micromol/L)]; p < 0.001) compared to controls
      (4.79 +/- 2.26 [(pmol/mg)/(micromol/L)]). Homocysteine, folate, vitamin B12, and
      neopterin showed no significant difference. Discriminant analysis provided CP
      alone as the best clinical marker with highest sensitivity and highest
      specificity for AD/MCI followed by the ratio of CP/Trp. ROC curve analysis
      provided the best result for CP/Trp. CONCLUSIONS: These preliminary results
      support the hypothesis that oxidative damage to proteins is directly connected
      with Trp degradation and Kyn pathway in the systemic immune activation.

PMID- 21086791
TI  - Bone marrow mitogen-stimulated direct antiglobulin test in a case of
      erythroblastic synartesis.
AB  - In this article we report a case of erythroblastic synartesis, a rare disease
      characterized by ineffective erythropoiesis, clusters of erythroblasts due to
      membrane invaginations, in which an autoimmune pathogenesis is hypothesized. We
      investigated the presence of anti-erythroblast autoimmunity in bone marrow
      cultures using a mitogen-stimulated direct antiglobulin test, a method reported
      to be able to disclose a latent autoimmunity in various diseases. The test
      revealed the presence of erythroblast-bound IgG, supporting the hypothesis of the
      autoimmune pathogenesis of erythroblastic synartesis. Supernatants induced the
      same specific morphological features, i.e erythroblastic clustering and
      diserythropoietic signs (multiple nuclei, nuclear inclusions, and intercellular
      bridges) in normal progenitors.

PMID- 21086790
TI  - Increased soluble OX40L is associated with carotid intima-media thickness.
AB  - BACKGROUND: Recent studies indicated that soluble OX40 ligand (OX40L) levels were
      increased in acute coronary syndrome. But the association between sOX40L and
      carotid intima-media thickness (IMT) has not been evaluated. METHODS: We measured
      plasma soluble OX40L (sOX40L) and Interleukin-10 (IL-10) levels in 35 patients
      with stable angina pectoris, 30 patients with risk factors of coronary artery
      disease, and 20 age and sex-matched controls. Carotid (IMT) was measured by B
      mode ultrasound. RESULTS: Plasma sOX40L levels were positively correlated with
      Carotid IMT (r = 0.376, P = 0.001) and inversely correlated with IL-10 (P = 
      0.394, P = 0.000). Multivariate linear regression analysis revealed that sOX40L
      (p = 0.019) was an independent predictor for Carotid IMT progression after
      adjusting for the classical cardiovascular risk factors. CONCLUSIONS: sOX40L is
      independently related to Carotid IMT, suggesting the possible relationship of
      OX40L to atherosclerosis. The positive relation of sOX40L to C-reactive protein
      (CRP) and the negative relation to IL-10 indicated the possible proinflammatory
      effects of OX40L on the pathogenesis of atherosclerois.

PMID- 21086792
TI  - Lipoprotein(a) and ageing.
AB  - BACKGROUND: Lipoprotein(a) (Lp(a)) is an independent risk factor for
      cardiovascular disease. There is as yet controversy on serum Lp(a) concentrations
      in the elderly population. METHODS: We investigated 2128 medical outpatients who
      consecutively attended our laboratory between January 2006 and June 2008 for
      Lp(a) and routine serum lipid assessment. The cohort included 299 (88 men and 211
      women) elderly outpatients aged > or = 75 yrs and 1829 (828 men and 1001 women)
      patients aged < 75 yrs. RESULTS: Compared with those aged <75 yrs, elderly male
      patients had an overall more favourable traditional lipid profile, including
      lower values of cholesterol, triglycerides, LDL-C, total to HDL-C ratio,
      atherogenic index of plasma and higher values of HDL-C. Conversely, no
      significant differences could be observed between women aged < 75 yrs and the
      elderly patients. In both genders, elderly patients had significantly higher
      Lp(a) median concentrations. However, after stratification of patients according
      to the current 300 mg/L cardiovascular risk threshold for Lp(a), the percentages
      of those > or = 75 yrs having Lp(a) levels above this threshold were marginally,
      but not significantly, higher in both genders (men: 28% versus 25%, p = 0.499;
      women: 35% versus 30%, p = 0.374). CONCLUSIONS: The results of the present
      investigation suggests that elderly patients have similar or even greater Lp(a)
      values than those observed in a general population aged < 75 yrs. Accordingly,
      elevated serum Lp(a) concentrations may be compatible with longevity.

PMID- 21086793
TI  - Investigation of GJB6 large deletions in Iranian patients using quantitative real
      time PCR.
AB  - BACKGROUND: Hearing loss is a serious sensory defect in the world. Mutations in
      the GJB2 and GJB6 genes are the major causes of autosomal recessive nonsyndromic
      hearing loss (NSHL). Recently, three major large deletions in the GJB6 gene
      including del(GJB6-D13S1830), del(GJB6-D13S1854), and a > 920 kb deletion have
      been reported to form double heterozygosity with GJB2. This may suggest that
      deletions involving GJB6 may be responsible for some NSHL. METHODS: We designed a
      real time SYBR green-based PCR to quantify a common deleted region in GJB6 gene.
      The amplified region covers the area which has been seen to be deleted in all of
      the above reports. We selected nine families heterozygous for different mutations
      in GJB2 gene to investigate the presence of deletions in the GJB6 gene. The
      samples were run along with controls for normal hearing and heterozygous and
      homozygous for GJB2 mutations to optimize our method. As a reference gene or
      external standard, a segment of the CLCN7 gene was also quantified as well.
      RESULTS: We did not detect any deletion in the GJB6 gene. CONCLUSIONS: Using this
      method, any deletion involving GJB6 gene can be detected in a rapid and sensitive
      way.

PMID- 21086794
TI  - Development of a high throughput single nucleotide polymorphism screening method
      for the cytochrome P450 1A2 polymorphisms CYP1A2*1C and CYP1A2*1F: are they
      useful as predictive markers in mental disorders?
AB  - BACKGROUND: The cytochrome P450 1A2 (CYP1A2) gene encodes one of the most
      important enzymes of the Phase I drug metabolism, which is involved in the
      metabolism of many lipophilic xenobiotics, such as haloperidol, theophylline,
      phenacetine, and others. The recently discovered single nucleotide polymorphisms
      CYP1A2*1C (-3860G-->A) in the 5' flanking region of the gene and CYP1A2*1F (-163C
      ->A) in intron 1 seem to interfere with the expression rate or catalytic function
      of the enzyme. Polymorphism carriers may either have a risk of reduced drug
      degradation and side effects, or may present with an increased induction of
      enzymatic activity resulting in clinical non-response to the prescribed therapy.
      We investigated two populations, a mental disease group and a healthy control
      group, to identify whether these two genetic variants are correlated with the
      general development of a mental disorder and if they could potentially be used as
      predictive markers for manifestation of the same. METHODS: Using specifically
      designed primers, we established a high-throughput multiplex screening realtime
      PCR method for the two polymorphisms on the CYP1A2 gene with the Roche
      LightCycler instrument. RESULTS: We analysed the two cohorts to identify whether
      one of the two described genetic variants may be associated with the
      manifestation of a mental disorder in general. For the CYP1A2*1C variant, we
      identified an allele frequency of 1.7% for both cohorts. For the CYP1A*1F
      polymorphism, we found an allele frequency of 74.5% for the mental disease group
      and 68.6% for the healthy control group. CONCLUSIONS: This new diagnostic method
      of multiplex detection may be helpful to routinely identify carriers of CYP1A2
      variants and to improve the therapeutic effectiveness by selection of the most
      appropriate therapeutic regimen. As a result of this pilot study, there appeared
      to be no significant correlation between the existence of one of the investigated
      genetic variants and the development of a mental disorder.

PMID- 21086795
TI  - The implications of case results.

PMID- 21086796
TI  - It is time to change our strategy.

PMID- 21086797
TI  - The three golden rules occlusion.

PMID- 21086799
TI  - Endodontic treatment planning in the fourth dimension.

PMID- 21086798
TI  - Autistic spectrum disorder: the challenge for dentists.
AB  - Those who actively work with children are, with increasing frequency,
      encountering patients who have been diagnosed with autistic disorders. Often,
      dentists may be the first healthcare providers to recognize that a 1- or 2-year
      old child has some type of extraordinary pervasive behavioral disorder that a
      parent, fearing the worst, may have suspected instinctively and emotionally but
      never faced objectively. Currently, there are no empirical biological tests (eg,
      blood tests or brain scans) for ASD that are reliable. The definitive diagnosis
      of ASD is usually made by pediatricians, psychologists, or psychiatrists who
      institute a process of analysis which involves a developmental and clinical
      history, tests for cognitive function, and assessment of receptive and expressive
      language skills. The etiology of ASD is an enigma. Highly regarded researchers
      are of the opinion that there is probably more than one cause since the disorder
      can have such disparate manifestations. Genetics, environmental poisons,
      neurologic psychopathy, dietary deficiencies, and allergies have all been
      implicated. Pervasive developmental disorders, Asperger's syndrome, Rett
      syndrome, and childhood degenerative disorders are all considered a part of the
      ASD group, but the distinction between the various entities is not always clear.
      Given the fact that the etiology and the increased incidence of the various ASDs
      are scientifically puzzling, treatment modalities tend to be wide ranging and
      very much trial and error, especially since there is no cure. Dental
      professionals who treat patients with ASDs should be knowledgeable about the
      special needs of not only these patients, but also of their parents.

PMID- 21086800
TI  - Reclaiming endodontics and reinventing restorative, Part I.

PMID- 21086801
TI  - Extraoral cementation of implant crowns.

PMID- 21086802
TI  - Clinical pearls for surgical implant dentistry: Part 3.

PMID- 21086803
TI  - Evidence-based treatment for the edentulous patient.

PMID- 21086804
TI  - Air abrasion: the new renaissance with an H2O twist.

PMID- 21086805
TI  - Effective hemostasis and tissue management.

PMID- 21086806
TI  - Accurate impression technique: a key to successful prosthetics.

PMID- 21086807
TI  - Water: the elixir of life.

PMID- 21086808
TI  - Sex and germs: always a risky mixture.

PMID- 21086809
TI  - Men's health.

PMID- 21086810
TI  - A short tale of some known knowns, some known unknowns and one major unknown
      unknown.

PMID- 21086811
TI  - Water world.

PMID- 21086812
TI  - Plumbing--vital to global health.

PMID- 21086813
TI  - If you have health you have hope, if you have hope you have everything.

PMID- 21086814
TI  - The implication of water on public health: the case of China.

PMID- 21086815
TI  - Need for community water fluoridation in areas with suboptimal fluoride levels in
      India.

PMID- 21086816
TI  - Blending skills for water gain.

PMID- 21086817
TI  - How health professionals can leverage health gains from improved water,
      sanitation and hygiene practices.
AB  - Emerging evidence suggests that widespread failure in coordination and
      collaboration between the health and WaSH sectors contributes to the substantive
      disease burden associated with inadequate water, sanitation and hygiene (WaSH).
      This results in missed opportunities at every level starting with access to water
      and sanitation and adequate hygiene practices in primary health facilities. This
      paper describes the application of an established health system functions
      framework to the WaSH sector and summarizes examples of successful health system
      action including the roles played by diverse health professionals.

PMID- 21086818
TI  - Interim report: review of evidence of the health impact of famine in Ethiopia.
AB  - Historical accounts of famines in Ethiopia go as far back as the 9th century,
      however, evidence on its impact on health only started to emerge from the 15th
      century onwards. Unfortunately, famine has been endemic in Ethiopia in the last
      few decades. The 1973 famine is reported to have claimed over 300,000 lives. In
      1985 approximately 10 million people were reported to be starving, with
      approximately 300,000 already dead and about 1000 dying daily. In the following
      years, droughts leading to food shortage have had local and national adverse
      health effects, in particular in 1999/2000. This paper describes the initial
      findings of a literature review of evidence on the health impact of droughts
      leading to famine in Ethiopia and highlights gaps in knowledge. The key finding,
      thus far, is the marked paucity of health impact data. This review also
      highlights the fact that adverse health impacts of famines are probably complex
      and long lasting. Interpretation of any health impact data is difficult as there
      are few baseline data to compare. Health effects also impact livelihoods.
      Livelihood disruption following famine does not just affect one generation but
      also subsequent generations. Surveillance systems are needed so that records of
      the health impacts of a drought that leads to famine can inform action. With
      climate change bringing increased likelihood of drought and famine in some parts
      of the world, the findings of this review could be beneficial not just for
      Ethiopia but also elsewhere.

PMID- 21086819
TI  - Water and health: a forgotten connection?
AB  - There are frequent and doom-laden messages concerning impending water shortages
      but the consequential negative effects on the availability of waters for healing
      and the factors underlying the decline in the use of water therapies in some
      parts of the world are ignored. This article reviews the evidence for the
      medicinal uses of water, past and present, showing how ancient Egyptian, Greek,
      Roman, Celtic and Hebrew societies all used water for medicinal purposes,
      sometimes in conjunction with herbal medicine. Water treatments consisted of
      hydrotherapy (techniques of therapeutic bathing and use of water), balneotherapy
      (therapeutic bathing in medicinal and thermal springs) and thalassotherapy (the
      therapeutic use of ocean bathing and marine products) and these treatments
      continue to be used to the present day although their use in the Anglo-Saxon
      world is diminised. Factors in this decline are the lack of research funding and
      the availability of allopathic medicine. In ancient society, the factors
      underlying the efficacious healing properties of water may have been ignored and
      its benefits instead attributed to divine sources. Latterday science, however,
      from the 19th century to the present, has isolated those factors in water that
      have health-giving properties.

PMID- 21086820
TI  - Will drivers for home energy efficiency harm occupant health?
AB  - The U.K. government has committed to an 80% reduction in carbon emissions by
      2050, with housing accounting for 27% of total current emissions. There are
      several drivers both to reduce emissions from homes and to reduce fuel poverty,
      promoting a range of building and behavioural measures in homes. The health
      benefits of warmer homes in winter have been described, but there has been less
      consideration of the potential negative impacts of some of these measures. We
      examine the changes in U.K. homes, and the possible consequences for health. The
      main concerns for health surround the potential for poor indoor air quality if
      ventilation is insufficient and the possible risks of overheating in heatwave
      conditions. This paper notes a limited evidence base and the need for further
      research on the health effects of energy-efficient homes, particularly with
      regard to ventilation.

PMID- 21086821
TI  - Including self-reported race to improve cancer surveillance data for American
      Indians and Alaska Natives in Washington state.
AB  - BACKGROUND: American Indians and Alaska Natives (AI/AN) are frequently
      misclassified as another race in cancer surveillance systems, resulting in
      underestimated morbidity and mortality. Linkage methods with administrative
      records have been used to correct AI/AN misclassification, but AI/AN populations
      living in urban areas, and those who self-identify as AI/AN race, continue to be
      under-ascertained. The aim of this study was to evaluate racial misclassification
      in two cancer registries in Washington State using an urban AI/AN patient roster
      linked with a list of Indian Health Service (IHS) enrollees. METHODS: We
      conducted probabilistic record linkages to identify racial misclassification
      using a combined demographic dataset of self-identified AI/AN patients of a
      large, urban Indian health center, and administratively-identified AI/AN enrolled
      with the IHS. Age-adjusted incidence rates were calculated for 3 linkage
      populations: AI/ AN originally coded in each cancer registry, post-linkage AI/AN
      identified through the IHS roster alone, and post-linkage AI/AN identified
      through either the urban or IHS file. RESULTS: In the state and regional cancer
      registries, 11% and 18%, respectively, of matched cases were originally coded as
      a race other than AI/AN; approximately 35% of these were identified by the urban
      file alone. Incidence rate estimates increased after linkage with the IHS file,
      and further increased with the addition of urban records. Matches identified by
      the urban patient file resulted in the largest relative incidence change being
      demonstrated for King County (which includes Seattle); the all-site invasive
      cancer rate increased 8.8%, from 443 to 482 per 100,000. CONCLUSIONS: Inclusion
      of urban and self-identified AI/AN records can increase case ascertainment in
      cancer surveillance systems beyond linkage methods using only administrative
      sources.

PMID- 21086822
TI  - Improving geocoding outcomes for the Nebraska Cancer Registry: learning from
      proven practices.
AB  - This report summarizes geocoding improvement experiments in the Nebraska Cancer
      Registry. An initial assessment of previous geocoding suggests that some proven
      geocoding procedures have not been followed, and overall results were
      unacceptable. This study concluded that when updating different address files
      from different time periods, it is sufficient to use the most recent street
      centerline database. The combination of match score of 80 and spelling
      sensitivity of 80 in ESRI's ArcGIS geocoder is sufficient for most geocoding
      purposes. Given the sizable number of unmatched addresses, the Google Maps
      geocoding service was used. A comparison of 1500 high-quality addresses that were
      matched by both Google Maps and ArcGIS geocoders shows that, in most cases, the
      location discrepancies between the two were acceptable. The median distance
      between each pair of 1500 coded locations was 36.6 meters, with an average of
      92.8 meters. Distance discrepancies were larger in urban fringe areas and smaller
      toward urban centers. It was concluded that by strictly following proven
      procedures including address coding specification, Internet-based White Pages for
      reverse address finding, and Internet-based geocoding, a 90% or even a 95% match
      rate is achievable.

PMID- 21086824
TI  - Implementing measures to improve cancer program practice profile report (CP3R)
      compliance rates for breast, colon, and rectal cancers.

PMID- 21086823
TI  - Obtaining data on comorbid diabetes among patients in a U.S. population-based
      tumor registry.
AB  - Comorbid diabetes mellitus has been shown to be associated with outcomes among
      cancer patients, but population-based data have been limited to elderly patients
      through linkages between the US National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) Program database and Medicare databases.
      Reporting of comorbidity to the population-based Connecticut SEER registry is not
      required, but the extent of voluntary reporting of comorbid diabetes was assessed
      in this preliminary study. Of 15,145 Connecticut residents diagnosed at age 20+
      years with invasive cancer in 2006, who were ascertained from 33 registry
      sources, 8688 (57.4%) from 21 sources were included in the analysis of comorbid
      diabetes. The prevalence of comorbid diabetes was 12.5%, and was lowest for
      patients with prostate cancer (8.5%) and highest for with liver-pancreas cancer
      (25.9%), consistent with the literature. Diabetes prevalence was substantial
      (9.5%) within the non-elderly subgroup aged 20-64 years at cancer diagnosis who
      comprised 45% of the 8688 patients. These results indicate an opportunity for
      future large-scale studies of the impact of diabetes on outcomes among all newly
      diagnosed cancer patients (both non-elderly and elderly) in the Connecticut SEER
      registry and other US central cancer registries.

PMID- 21086825
TI  - Training and retaining staff in the cancer registry.

PMID- 21086826
TI  - The inquiry and response system: knowledge is power: chapter 7, Cancer program
      standards, 2009, revised edition.

PMID- 21086827
TI  - Adobe Reader tools for CSv2 and the Heme coding manual.

PMID- 21086828
TI  - Act like you belong.

PMID- 21086829
TI  - Fast track training needed to hit health visitor target.

PMID- 21086830
TI  - The white paper offers infection control nurses new opportunities.

PMID- 21086831
TI  - Using the lived experiences of patients with Clostridium difficile infection to
      improve care.
AB  - AIM: To better understand the lived experiences and needs of patients who have
      Clostridium difficile infection. METHOD: Interviews were conducted with 15
      patients in an acute hospital using an interpretative phenomenological approach.
      RESULTS: Experiences vary and depend onthe severity of each individual patient's
      condition, among other factors. Four main themes were identified: physical
      suffering impacting on activities of daily living; lack of control over bowel
      function; a lack of understanding of the illness; and issues around privacy and
      dignity. CONCLUSION: Nursing and medical staff need a better understanding of the
      experiences of patients who have C difficile in order to provide them with the
      knowledge, reassurance and dignity they need.

PMID- 21086832
TI  - How to reduce the negative psychological impact of MRSA isolation on patients.
AB  - MRSA is contagious and difficult to treat, and the isolation of infected patients
      is recommended by the Department of Health. However, isolation can have a
      negative psychological impact on patients and is controversial. This literature
      review explores the effects of isolation based on three themes: isolation
      environment and psychological impact; stigma of MRSA; and nursing care.

PMID- 21086833
TI  - Developing satellite roles within infection prevention teams to fulfil
      responsibilities.
AB  - Changing demands on infection control services require managers to think about
      roles and responsibilities within the infection prevention team. Satellite roles
      focus on specific job functions to complement the role of the clinical nurse
      specialist and are related to one area or subject within the remit of the
      clinical nurse specialist. This article outlines the development of satellite
      roles in an infection control team, which resulted in reduced healthcare
      associated infections, improved clinical practice and patient satisfaction.

PMID- 21086834
TI  - Using the Waterlow tool to predict Clostridium difficile infection risk in
      hospital settings.
AB  - C difficile is the most important cause of infectious healthcare acquired
      diarrhoea and risk of infection is a public concern. Many acute and primary care
      trusts are working to further reduce rates of C difficile and targets have been
      set. Global reduction strategies include prudent antibiotic prescribing and
      intensive cleaning programmes. While risk assessment tools for C difficile exist,
      they are not easy to use in hospital. This article introduces an inexpensive and
      easy to use assessment tool and outlines how nurses can apply a reduction
      strategy using it to identify patients who are at risk on admission and then
      target interventions to reduce this risk.

PMID- 21086835
TI  - Pregnancy checks before surgery.

PMID- 21086836
TI  - Preparation for a post antibiotic era must start now.

PMID- 21086837
TI  - Our small roles are part of a bigger picture.

PMID- 21086839
TI  - Patients benefit from quality targets.

PMID- 21086838
TI  - Acute trusts rely on nurses to earn quality payments.

PMID- 21086840
TI  - Why are we doing so badly in treating incontinence?

PMID- 21086841
TI  - Developing a joined up approach to smoking cessation in primary and secondary
      care.
AB  - Nurses are well placed to give patients help and advice on giving up smoking.
      This article describes how a groundbreaking nurse led project has increased
      referrals to smoking cessation services and encouraged thousands of patients to
      quit. It discusses the importance of healthcare professionals working together to
      support patients to stop smoking and the need for training to ensure staff are
      engaged with the "quit journey".

PMID- 21086842
TI  - Understanding the subjective experiences and needs of patients as they approach
      death.
AB  - When patients are approaching the end of life their spiritual as well as physical
      needs should be considered. This article considers how nurses can best support
      patients who are dying and work to ensure they experience a peaceful transition
      to death. Attending to their spiritual needs is shown to be of utmost importance;
      the near death and end of life experiences that some patients may have are also
      taken into consideration.

PMID- 21086843
TI  - Using biofeedback to treat constipation, faecal incontinence and other bowel
      disorders.
AB  - Biofeedback is a behavioural therapy used to treat people with bowel dysfunction,
      such as constipation or faecal incontinence, who do not respond to standard
      treatment. This article highlights how biofeedback therapy is used to treat these
      problems and improve patients' quality of life.

PMID- 21086844
TI  - Improving the quality of nursing documentation on an acute medicine unit.
AB  - BACKGROUND: An action research project was undertaken to explore issues
      underpinning poor quality documentation and how improvement in assessment can be
      achieved and sustained. AIM: To improve nursing documentation, as well as the
      quality of nursing assessments and evaluation in an acute medicine unit using
      anaction research approach. METHOD: Nurses from an acute medicine unit helped
      develop a new process for assessment documentation. Five pieces of documentation
      were radically changed and three new pieces developed. During testing, four
      cycles of action research w ere completed; as a result, focused interventions
      were made to the documentation and assessment process to promote improvement in
      the areas that demonstrated poor completion or compliance. The new documentation
      was evaluated for degree of completion and compliance with the new process.
      RESULTS DOCUMENTATION: the quality of entries recorded, and compliance improved.
      Documentation was also more up to date. Staff commitment helped unravel issues
      underpinning poor completion/compliance to the original documentation and
      assessment process. CONCLUSION: Care planning must be taught in pre-registration
      training as a fundamental principle of care. Understanding issues pertinent to a
      busy area and designing a process that makes completion of documentation easier
      means changes can be sustained long after the active stages of action research
      have been completed.

PMID- 21086845
TI  - NICE aims to save thousands of lives with guidance on preventing cardiovascular
      disease.

PMID- 21086846
TI  - Nurses need to speak the language of compassion.

PMID- 21086847
TI  - The phoney war just got a bit more real.

PMID- 21086848
TI  - Notes for the new nurse.

PMID- 21086849
TI  - Surviving and thriving in the workplace. Soy, probiotics...and willow trees?

PMID- 21086850
TI  - Health policy report.

PMID- 21086851
TI  - Breathing the miasma: are you prepared to protect your patients from the flu?

PMID- 21086852
TI  - Stressing the importance of dealing with stress.

PMID- 21086853
TI  - The nursing list. "Do's & don'ts" when dealing with childhood obesity.
AB  - "If you're not part of the solution, you're part of the problem." This saying can
      go far when it comes to nurses doing all they can to help literacy challenged
      families deal with childhood obesity. For nurses, the challenge is to be an
      educator now so as not to have to be a provider later--helping families prevent
      the unhealthy situation in hopes that the condition never presents itself.

PMID- 21086854
TI  - What are medical homes? What is the state of medical home development in Ohio?

PMID- 21086855
TI  - Workplace wisdom. Safe/no lifting culture can prevent injuries.

PMID- 21086857
TI  - Cultural differences in asymmetric beliefs of interpersonal knowledge in vertical
      and horizontal relationships.
AB  - Previous studies have reported that our interpersonal knowledge shows an
      asymmetry; that is, we tend to believe that we know and understand other people's
      thoughts and feelings better than other people know and understand our own
      thoughts and feelings. In the present study, the authors compared American (114
      men, 192 women) and Korean (99 men and 98 women) students to examine whether the
      asymmetry is greater in collectivistic than in individualistic culture in two
      types of relationships: horizontal (with best friends) and vertical (with
      parents). On all three items--Know, Understand, and Visibility--asymmetry was
      found for both horizontal and vertical relationships. Further, the Understand and
      Visibility items showed greater asymmetry for the Korean group than for the
      American group. It was concluded that asymmetry is greater in collectivistic than
      in individualistic culture. The cultural differences can be explained by self
      consistency, sensitivity to social consequences, parent-child interaction, and
      living arrangement.

PMID- 21086856
TI  - Evidence that episodic memory impairment during tobacco abstinence is independent
      of attentional mechanisms.
AB  - Previous studies have demonstrated reductions in episodic memory during nicotine
      withdrawal. However, these studies have been unable to dissociate memory
      reductions from losses in attention associated with tobacco abstinence. In the
      present study, the authors sought to determine whether episodic memory reduction
      is a primary effect of nicotine withdrawal during tobacco abstinence. Heavy
      smokers were tested when smoking normally and following 24 hrs of abstinence.
      Participants were tested with a recognition memory task in which items were
      studied under full and divided attention conditions. Forward digit span and
      backward digit span were also included as control measures. Withdrawal was
      associated with a reduction in memory performance that was independent of
      attention at encoding. The authors conclude that impairment of episodic memory is
      a primary effect of nicotine withdrawal during tobacco abstinence. Further
      research is required to determine if this is associated with continued use of
      tobacco and cessation failures.

PMID- 21086858
TI  - Using system-wide trust theory to make predictions about dependence on four
      diagnostic aids.
AB  - System-wide trust strategy can occur when operators are exposed to multiple aids
      of different reliabilities. D. Keller and S. Rice (2009) showed that when a
      perfectly reliable aid was presented concurrently with an unreliable aid,
      participants tended to treat the 2 aids as a unit (system-wide trust) rather than
      as different units with different reliabilities (component-specific trust).
      Limitations to their original study prevented the authors from making strong
      conclusions about a pervasive system-wide trust strategy across domains. The
      current study revisits this theoretical issue by increasing the number of aids,
      manipulating the amount of information and feedback participants were given, and
      using a single-task paradigm rather than a dual-task paradigm. Results were
      conclusive. While providing information and feedback were beneficial to overall
      performance, dependence measures indicated that system-wide trust strategies were
      pervasive across almost all of the manipulations. We discuss the theoretical and
      applied implications of these data.

PMID- 21086859
TI  - The effect of humor on memory: constrained by the pun.
AB  - In a series of experiments, we investigated the effect of pun humor on memory. In
      all experiments, the participants were exposed to knock-knock jokes in either the
      original form retaining the pun or in a modified form that removed the pun. In
      Experiment 1, the authors found that pun humor improved both recall and
      recognition memory following incidental encoding. In Experiment 2, they found
      evidence that rehearsal is not the cause of the humor effect on memory. In
      Experiments 3 and 4, the authors found that the constraints imposed by puns and
      incongruity may account for the humor effects observed. Puns constrain and limit
      the information that can fit in the final line of a joke and thus make recall
      easier.

PMID- 21086860
TI  - National Hospital Discharge Survey: 2007 summary.
AB  - OBJECTIVES: This report presents national estimates of hospital inpatient care in
      the United States during 2007 and selected trend data. Numbers and rates of
      discharges, diagnoses, and procedures are shown by age and sex. Average lengths
      of stay are presented for all discharges and for selected diagnostic categories
      by age and by sex. METHODS: The estimates are based on data collected through the
      2007 National Hospital Discharge Survey, an annual national probability sample
      survey of discharges from nonfederal, general, and short-stay hospitals. Sample
      data are weighted to produce annual estimates of inpatient care, excluding
      newborns. Diagnoses and procedures are coded using the International
      Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: In
      2007, there were an estimated 34.4 million hospital discharges, excluding
      newborns. The total hospitalization rate leveled off from 1995 to 2007 after
      declining during the period from 1980 to 1995. Throughout the period from 1970 to
      2007 the rates for those aged 65 years and over were significantly higher than
      the rates for the younger groups. Although those aged 65 years and over accounted
      for only 13 percent of the total population, they comprised 37 percent of
      hospital discharges and 43 percent of hospital days. One-quarter of inpatients
      under age 15 years were hospitalized for respiratory diseases. There were 45
      million inpatient procedures during 2007 and 15 percent of these were
      cardiovascular. Males aged 45-64 and 65 years and over had higher cardiac
      catheterization rates than females in these age groups each year from 1997 to
      2007. From 2002 to 2007 the rate of inpatient cardiac catheterization procedures
      declined.

PMID- 21086861
TI  - The NLN Education Competencies Model: our foundation for the future.

PMID- 21086863
TI  - Faculty matters: Suzan Kardong-Edgren.

PMID- 21086862
TI  - Energetic engagement: the leadership challenge for nurse educators.

PMID- 21086864
TI  - Cultural competency of graduating BSN nursing students.
AB  - Providing culturally appropriate care is an essential nursing competency for new
      graduates. Multiple curricular approaches are being used to achieve this end.
      When measured by Campinha-Bacote's Inventory for Assessing the Process of
      Cultural Competency Among Healthcare Professionals-R, graduating students (n =
      515) from six different BSN programs scored, on average, in the culturally aware
      range. These results suggest that no one curricular approach is proving to be
      more effective than another in achieving essential cultural competency.

PMID- 21086865
TI  - A peer mentor tutor program for academic success in nursing.
AB  - Due to the difficult and rigorous nature of nursing education, student retention
      and attrition are major concerns for faculty. This article describes the
      implementation and outcomes of a peer-based mentor tutor program (PMTP) for at
      risk students in a traditional baccalaureate program. Funding was obtained to
      provide scholarship incentives for student participants and cover costs of
      training and materials. Criteria were determined for the selection of student
      mentors-tutors and the identification of at-risk students. Interventions
      consisted of weekly PMTP sessions offered for the first four semesters of nursing
      courses. Course grades were used to determine outcome differences between control
      and intervention groups. Students in the intervention group were found to score
      significantly higher than the control group on both summative and final grades.

PMID- 21086866
TI  - A constructivist model for teaching evidence-based practice.
AB  - The Institute of Medicine has reported that it takes roughly 17 years for
      evidence generated through research to move into clinical practice. Bridging that
      gap is an urgent need and will require educators to rethink how nurses are
      prepared for evidence-based practice. The constructivist theory for learning--in
      which it is assumed that students construct knowledge and meaning for themselves
      as they learn--may provide a framework for a redesigned baccalaureate curriculum,
      one that supports evidence-based practice throughout a nursing student's
      education.

PMID- 21086867
TI  - Academic and clinical immersion in an accelerated nursing program to foster
      learning in the adult student.
AB  - Second-degree accelerated nursing programs provide an expedited pathway to enter
      the nursing profession. Most students in such programs are adult learners with
      high expectations for their own performance and equally high expectations for the
      curriculum of the chosen program. Clinical and academic immersions are curriculum
      strategies that are particularly suited to the adult learner in a second-degree
      accelerated program. This article discusses the development of an accelerated
      program, with a focus on the intended and unexpected challenges and outcomes
      associated with planning and implementing immersion learning for academic and
      clinical experiences. Content linkage as a teaching strategy is also described.
      The immersion year enhances collaboration and socialization among students,
      faculty, and staff nurses.

PMID- 21086868
TI  - Practical considerations in establishing sustainable international nursing
      experiences.
AB  - An understanding of global health and the development of cultural competence are
      important outcomes of today's baccalaureate nursing programs. Thoughtfully
      designed international experiences can provide excellent opportunities to achieve
      those outcomes. Based on 16 years of providing international experiences within a
      baccalaureate curriculum, components are identified that contribute to the
      development of a sustainable international program. Areas addressed in the
      article are evaluating the fit with university and college mission, establishing
      the program within the university operational structure, selecting faculty and
      students, developing sites, designing a course, and program evaluation.

PMID- 21086869
TI  - HeartCode BLS with voice assisted manikin for teaching nursing students:
      preliminary results.
AB  - The purpose of this study was to evaluate the effectiveness of HeartCode BLS, a
      self-directed, computer-based course for obtaining basic life support (BLS)
      certification. For part 2 of the course, students learned and practiced their
      cardiopulmonary resuscitation (CPR) psychomotor skills on a voice assisted
      manikin (VAM). Students from 10 schools of nursing were randomly assigned to two
      types of CPR training: HeartCode BLS with VAM or the standard, instructor-led
      (IL) course with manikins that were not voice assisted; 264 students trained
      using HeartCode BLS and 339 had an IL course. When students passed their
      respective courses and were certified in BLS, their CPR skills were tested using
      the Laerdal PC SkillReporting System. Students who trained using HeartCode BLS
      and practiced their CPR skills on VAMs were significantly more accurate in their
      ventilations, compressions, and single-rescuer CPR than students who had the
      standard, IL course with regular manikins.

PMID- 21086870
TI  - High-fidelity patient simulation: considerations for effective learning.
AB  - This article explores a case of the implementation of high-fidelity simulation
      (HFS) in an undergraduate preregistration nursing program in a Canadian school of
      nursing. A small practice collaborative project to develop reusable simulation
      resources for team-based simulations is described, using HFS technology.
      Considerations for effective learning resulting from faculty and student
      evaluations of the project are discussed. Students identified positive learning
      experiences and indicated that real-time patient status changes proved valuable
      to them. Also, using these techniques offered a safe environment for improving
      competence. The use of reflective debriefing appeared to be a focal area for
      learning that requires emphasis in the planning of HFS experiences. This
      template, team-focused learning approach also appeared to offer a cost-efficient
      strategy for HFS.

PMID- 21086871
TI  - Immersive virtual reality simulations in nursing education.
AB  - This article explores immersive virtual reality as a potential educational
      strategy for nursing education and describes an immersive learning experience now
      being developed for nurses. This pioneering project is a virtual reality
      application targeting speed and accuracy of nurse response in emergency
      situations requiring cardiopulmonary resuscitation. Other potential uses and
      implications for the development of virtual reality learning programs are
      discussed.

PMID- 21086872
TI  - Back to school: what's in your students' backpacks?

PMID- 21086873
TI  - Ageless wonders.

PMID- 21086874
TI  - Using an honors program to engage undergraduate students in research.

PMID- 21086875
TI  - The ACES framework: guiding nursing education and clinical practice to provide
      competent, individualized, and humanistic care to older adults.

PMID- 21086877
TI  - A prospective crossover pilot study to evaluate the use of a topical wound gel in
      patients with cutaneous toxicity caused by epidermal growth factor receptor
      inhibitors.
AB  - One of the dose-limiting toxicities of epidermal growth factor receptor
      inhibitors (EGFRIs) is a papulopustular rash that is often pruritic and painful.
      Secondary skin infection can occur from scratching to relieve the pruritus.
      Studies suggest that this rash might be a surrogate marker for efficacy;
      therefore, effective rash management is needed to allow patients to use EGFRIs
      without unnecessary dose modifications. In this single-center, prospective,
      crossover study, we evaluated the use of a topical gel (Regenecare Wound Gel) for
      relieving the pruritus and pain of EGFRI-induced rash among oncology patients.
      The secondary end points were patient satisfaction, adverse effects, and EGFRI
      dose modifications. At the occurrence of grade 2 skin rash, patients started
      applying the study gel to the right side of their face; after 1 week, they began
      applying it to both sides of their face for up to an additional 5 weeks. Each
      week, providers performed a facial evaluation and patients rated their symptoms
      and satisfaction on questionnaires. Of the 20 patients enrolled, 13 were
      evaluable. Reduction in itch at the end of week 1 was greater on the right
      (treated) side in 69% of patients greater on the left (untreated) side in 8%, and
      the same in 23% (P = 0.01). The pattern was similar for pain, but the differences
      were not significant. On average, patients rated the gel as being moderately to
      extremely effective for alleviating symptoms, improving rash appearance, and
      promoting healing and found it easy to apply. No adverse effects were documented.
      Four patients (31%) required EGFRI dose modifications because of rash. Taken
      together, these findings suggest that the topical wound gel is effective in
      relieving rash-associated itching in patients receiving EGFRIs and is associated
      with high patient satisfaction.

PMID- 21086876
TI  - Longitudinal effects of social support and adaptive coping on the emotional well
      being of survivors of localized prostate cancer.
AB  - Survivors of prostate cancer experience treatment-related physical side effects
      that can compromise emotional well-being for years post-treatment. There is
      limited research investigating how social support and the use of coping may
      affect the emotional well-being of this population following treatment. The aim
      of this study was to investigate how social support and coping impact emotional
      well-being 2 years after treatment in survivors of localized prostate cancer who
      have received either radical prostatectomy or radiotherapy. Psychosocial and
      disease-specific measures were administered to an ethnically and demographically
      diverse sample of 180 men treated for localized prostate cancer at baseline and
      at 2-year follow-up. Regression analyses demonstrated that higher levels of
      social support at baseline predicted better emotional well-being 2 years later.
      Furthermore, higher levels of adaptive coping at baseline partially mediated the
      relationship between social support and emotional well-being. Supportive
      relationships may contribute to improved emotional well-being following treatment
      by facilitating the use of adaptive coping strategies. Attention should be given
      to strengthening social support networks and educating survivors of prostate
      cancer on adaptive coping techniques.

PMID- 21086878
TI  - Androgen deprivation therapy in patients with advanced prostate cancer.

PMID- 21086879
TI  - Preventing and managing vesicant chemotherapy extravasations.
AB  - Although vesicant chemotherapy extravasations cannot be entirely prevented, the
      risk of extravasation can be reduced by adhering to guidelines for safe vesicant
      administration. These include engaging patients in extravasation-prevention
      efforts, thoroughly assessing patients receiving vesicants, selecting an
      appropriate administration site for peripheral vesicant administration, and
      checking for a blood return prior to and during vesicant administration. In
      addition, whenever an extravasation occurs or is suspected, vesicant
      administration must immediately cease, and the appropriate antidote or treatment
      needs to be promptly administered.

PMID- 21086880
TI  - "Tell me what you understand": the importance of checking for patient
      understanding.

PMID- 21086881
TI  - Dimensional versus categorical use of the PHQ-9 depression scale among persons
      with non-small-cell lung cancer: a pilot study including quality-of-life
      comparisons.
AB  - The debate over the relative usefulness of categorical (yes/no) versus
      dimensional (continuous scales) assessments for determining mental illness has
      been running strong for nearly a half century. In order to address the utility of
      each of these assessment methods within the cancer population, in the present
      study, the dimensional and categorical scoring systems of the nine-item Patient
      Health Questionnaire (PHQ-9) for depression were compared among patients (n = 14)
      in the pretreatment stages for locally advanced non-small-cell lung cancer
      (NSCLC). Also included in the study was an additional dimensional measure of
      depression, the Beck Depression Inventory-II (BDI-II). As predicted, dimensional
      assessments resulted in higher estimates of depression than did the categorical
      assessment. As predicted, the dimensional depression assessments, including the
      PHQ-9 and the BDI-II, which showed depression prevalence rates of 43% and 36%,
      respectively, produced higher estimates of depression than did the categorical
      system of the PHQ-9, whose use did not result in any patients being diagnosed
      with major depression or other depression. Also, as predicted, in terms of
      quality of life, patients found to be depressed by both the BDI-II and the
      dimensional PHQ-9 reported significantly worse physical, functional, and
      emotional well-being than did their nondepressed counterparts. Study findings
      suggest a need for further investigation into the possibility that patients who
      score highly on the dimensional scoring system of the PHQ-9 but at values below
      threshold on the more commonly accepted categorical scoring system of the same
      measure would benefit from consideration for psychotherapeutic treatment.

PMID- 21086882
TI  - Are free drug samples in the best interest of our patients?

PMID- 21086883
TI  - Metoclopramide for migraines; how to stock a first aid kit.

PMID- 21086884
TI  - Unusual depressed areas on the arm and buttock.

PMID- 21086885
TI  - Concussion: assessment of traumatic brain injuries.

PMID- 21086886
TI  - Neuroblastoma: management of a common childhood malignacy.

PMID- 21086887
TI  - Small bowel necrosis in association with jejunal tube feeding.
AB  - Early recognition and appropriate treatment of bowel ischemia is imperative to
      reduce morbidity and mortality in any situation, including in conjunction with
      enteral tube feeding. GI intolerance can manifest as increased nasogastric tube
      output, unexplained abdominal pain/distension, and pneumatosis intestinalis in
      critically ill patients who are on tube feedings and may be experiencing periods
      of splanchnic hypotension. Recommendations are to immediately cease tube feedings
      when these signs and symptoms are recognized, and total parenteral nutrition
      should be considered. Surgical exploration during the early stages should be
      considered to prevent the usual and fatal catastrophic cascade of widespread bowl
      infarction.

PMID- 21086888
TI  - Educating patients about the value of umbilical cord blood donation.

PMID- 21086889
TI  - Physician assistants working in the Department of Veterans Affairs.
AB  - There is broad consensus among medical workforce analysts that the demand for
      physician assistants (PAs), physicians, nurses, allied health, and other medical
      providers has substantially increased since the late 1990s. While researchers
      tend to examine the deployment of various providers in private medical offices,
      they often overlook federally-employed PAs. Since the late 1980s, the Department
      of Veterans Affairs (VA) has been a major employer of PAs. The demand for
      services is projected to increase by 30% over the next decade as the VA undergoes
      expansion. We examined the characteristics of PAs in the Veterans Health
      Administration (VHA), the medical arm of the VA. In 2010, 1,878 PAs were employed
      in 153 VA medical centers and many of the more than 900 community-based
      outpatient clinics. The majority work full time, and 49% are female. VHA PAs are
      distributed broadly across medical services (38%), surgery (47%), mental health
      (11%), and other services (4%). Thirty-one percent of PAs have prior military
      experience. The average years of VHA PA employment is 10.5, and the average age
      of a VHA PA is 49 years (range 23-74 years); one-third (34%) are within 5 years
      of retirement eligibility. Annual attrition for PAs is 9%, consistent with
      doctors, nurses, and pharmacists in the VHA. Projected demand for PA services in
      the VHA is expected to grow to 2,550 by 2018. Strategies are under way to improve
      the PA workforce in the VA.

PMID- 21086891
TI  - Serving the underserved.

PMID- 21086890
TI  - Irritable bowel syndrome: relieving the symptoms, and the frustration.

PMID- 21086892
TI  - Quick recertification series: Chlamydia.

PMID- 21086893
TI  - Quick recertification series. Gonorrhea.

PMID- 21086894
TI  - When the patient asks. Can folic acid lower heart attack risk?

PMID- 21086896
TI  - Rare conditions: where do primary care and genetic diseases intersect?

PMID- 21086895
TI  - A boy's ankle injury reveals a more serious condition.

PMID- 21086897
TI  - Case of the month. Acute myocardial infarction (MI).

PMID- 21086898
TI  - Sarcoidosis requiring systemic treatment: why not a steroid-sparing regimen up
      front?

PMID- 21086899
TI  - Ultrasound endoscopy (EBUS, EUS) as a sophisticated tool for morphological
      confirmation of sarcoidosis: do we need to find new answers for an old quest?

PMID- 21086900
TI  - Epithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary
      fibrosis.
AB  - New paradigms have been recently proposed in the pathogenesis of idiopathic
      pulmonary fibrosis (IPF), evidencing that in IPF the cumulative action of an
      accelerated parenchymal senescence determined by either telomere dysfunction or
      genetic defects, together with the concurrent noxious activity of tobacco
      smoking, are able to severely compromise the regenerative potential of
      parenchymal epithelial stem cells, triggering a cascade of molecular signals and
      events (scarring, bronchiolar proliferation, abnormal remodelling) eventually
      leading to severe and irreversible functional impairment. New pathogenic schemes
      focus on the complex molecular mechanisms driving in a vicious circle the
      different signalling pathways (e.g. Wnt/ -catenin, TGF-beta, caveolin-1, etc.)
      potentially involved in epithelial-mesenchymal transition and irreversible lung
      remodelling.

PMID- 21086901
TI  - Is tobacco smoking protective for sarcoidosis? A case-control study from North
      India.
AB  - BACKGROUND: While tobacco smoking is commonly believed to be negatively
      associated with the occurrence of sarcoidosis, the relationship of environmental
      tobacco smoke (ETS) exposure with sarcoidosis is largely un-explored. We studied
      the impact of active smoking and ETS exposure on disease severity in newly
      diagnosed cases of sarcoidosis from India. METHODS: Data on demographic
      variables, smoking habits and exposure to environmental tobacco smoke (ETS) among
      non-smoker sarcoidosis patients was collected prospectively. Presence of smoking
      and ETS exposure were compared among cases and controls. Among the sarcoidosis
      patients, clinical manifestations, radiology, spirometry and histopathological
      grading of lung biopsy were compared between the smokers vs. non-smokers and ETS
      exposed vs. not-exposed. RESULTS: We studied 98 newly diagnosed cases of
      sarcoidosis and 196 age, sex and religion- matched healthy volunteers. The study
      group comprised of 62 (63%) men and 36 (37%) women. The prevalence of smoking was
      similar in cases and controls (12.2% vs. 15.3%, p = 0.48). Among the never smoker
      patients with sarcoidosis, 20 (23%) reported ETS exposure vis-a-vis 57 (34%) in
      the matched controls. A conditional logistic regression analyses showed
      insignificant negative association with active smoking (OR 0.75; 95% CI, 0.35
      1.56) or ETS exposure (OR 0.58; 95% CI, 0.32-1.06) after adjusting for age,
      gender, religion, and education. There were no differences in the clinical
      manifestations, radiological staging, spirometry and histopathological grading of
      lung biopsy in any of the group comparisons studied. CONCLUSION: Smoking or ETS
      exposure may not have significant negative association with sarcoidosis. Also,
      tobacco smoke might not have any effect on the clinical behavior or disease
      severity in sarcoidosis. The belief that smoking is protective for sarcoidosis is
      not substantiated in this study and appears to be misfounded.

PMID- 21086902
TI  - Significance of plasma NT-proBNP levels as a biomarker in the assessment of
      cardiac involvement and pulmonary hypertension in patients with sarcoidosis.
AB  - BACKGROUND: Cardiac involvement and pulmonary hypertension (PH) are life
      threatening complications in sarcoidosis. OBJECTIVE: This study aimed to
      investigate the utility of plasma NT-proBNP in the assessment of these conditions
      in sarcoidosis patients. STUDY DESIGN AND METHODS: A prospective, observational
      study was performed on 150 consecutive Japanese sarcoidosis patients. Doppler
      echocardiography was performed in all subjects, and those who were successfully
      evaluated for PH status were included in the analysis. Cardiac sarcoidosis was
      diagnosed based on Japanese guidelines, and PH was defined as estimated systolic
      pulmonary artery pressure (sPAP) > or = 35 mmHg. The diagnostic accuracy of NT
      proBNP according to the presence of cardiac sarcoidosis and PH was assessed based
      on receiver-operator characteristic (ROC) curves. RESULTS: 130 subjects were
      successfully evaluated for PH status. Of these, 29 met the diagnostic criteria of
      cardiac sarcoidosis, and 21 were diagnosed with PH. Plasma NT-proBNP levels were
      significantly higher in patients with cardiac sarcoidosis (p < 0.0001). Stepwise
      regression analysis showed that presence of cardiac sarcoidosis, decreased
      ejection fraction and increased sPAP were all independently associated with
      higher plasma NT-proBNP levels. Plasma NT-proBNP showed good accuracy in
      identifying patients with cardiac sarcoidosis (area under the ROC curve; AURC =
      0.913). However, even when patients with cardiac sarcoidosis were excluded,
      plasma NT-proBNP levels could not be used reliably to identify patients with PH
      (AURC = 0.681). CONCLUSION: In patients with sarcoidosis, plasma NT-proBNP levels
      are a useful biomarker to identify cardiac involvement, but not to identify PH.

PMID- 21086903
TI  - Perceptions and beliefs in sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a chronic multisystem disease with a high prevalence
      of depression although this is often not recognised. It is not known how patients
      perceive their disease or the medications required for treatment. We hypothesised
      that perceptions of illness and beliefs about medications may relate to
      psychological distress in this condition. METHODS: 81(42 female) patients with
      sarcoidosis completed the following: Hospital Anxiety and Depression Scale,
      Illness Perception Questionnaire, Beliefs about Medications Questionnaire.
      Demographic and clinical data were collected and the physician's perception of
      symptom severity and relationship to sarcoidosis recorded. RESULTS: The
      prevalence of depression (23%) and anxiety (33%) was high and related to self
      reported symptoms of sarcoidosis. Those on current treatment reported different
      illness perceptions than those not, and illness perceptions related to anxiety
      and depression scores. The majority of the sample felt that sarcoid medications
      were unnecessary but few patients reported concerns about potential adverse
      consequences of taking them. Beliefs about medications were related to illness
      perceptions but not associated with anxiety or depression scores or with clinical
      perception of disease state. There were significant gender differences in
      perceptions of illness and beliefs about medications. CONCLUSIONS: These data
      confirm earlier reports that anxiety and depression are common in patients with
      sarcoidosis and in turn perceptions of illness impact on emotional wellness in
      this disorder. Use of the Illness Perceptions Questionnaire in clinical practice
      may help to identify those patients who would benefit from interventions to
      change their perceptions of illness.

PMID- 21086904
TI  - Minimally invasive diagnosis of sarcoidosis by EBUS when conventional diagnostics
      fail.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial fine-needle aspiration
      (EBUS) is a minimally invasive method used routinely for mediastinal staging of
      patients with lung cancer. EBUS has also proved to be a valuable diagnostic tool
      for patients with different intrathoracic lesions who remain undiagnosed despite
      bronchoscopy and CT-guided fine-needle aspiration. OBJECTIVE: The present study
      focused on EBUS for diagnosing sarcoidosis. DESIGN: During a 3-year period 308 of
      601 patients who underwent EBUS at our institution were referred for further
      diagnostic of a radiologically suspicious lesion in the lung parenchyma (n =
      195), enlarged lymph nodes in the mediastinum (n = 89), a suspicious tumor in the
      mediastinum or pleural disease (n = 24) but no one had a definite histological
      diagnosis. All charts were reviewed retrospectively. RESULTS: Of the 308 patients
      43 (14%) were eventually diagnosed with sarcoidosis. Thirty-three (77%) were
      diagnosed with EBUS. In the remaining 10 patients EBUS did not provide adequate
      tissue samples in 4 (9%) and in 6 patients (14%) EBUS provided adequate tissue
      but no definite diagnosis. EBUS was significantly better to establish the
      diagnosis in patients with enlarged mediastinal lymph nodes compared with
      isolated lung parenchymal involvement (85% vs 63%, p < 0.05). CONCLUSION: EBUS is
      a valuable minimally invasive diagnostic modality to establish the diagnosis of
      sarcoidosis of unselected patients with undiagnosed intrathoracic lesions after
      conventional work up--particularly if patients have enlarged mediastinal lymph
      nodes. This minimally invasive procedure provides a final diagnosis without
      exposing the patient to the risk of complications from more invasive procedures.

PMID- 21086905
TI  - C-reactive protein predicts response to infliximab in patients with chronic
      sarcoidosis.
AB  - BACKGROUND: This study assessed the value of C-reactive protein as a predictor of
      disease severity and response to infliximab therapy in patients with chronic
      pulmonary sarcoidosis. DESIGN: Sera were collected through week 52 from 138
      patients with chronic pulmonary sarcoidosis who received placebo or infliximab in
      a randomized, double-blind, placebo-controlled study. We evaluated the response
      to therapy by baseline CRP using a dichotomous cutpoint (0.8 mg/dL) for the
      change from baseline in percent-predicted forced vital capacity (FVC), Saint
      George's Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), Borg's
      CR10 dyspnea score, and Physician Organ Assessment (POA). RESULTS: CRP was
      elevated in 36% of patients at baseline, and was significantly reduced by
      infliximab by week 2. Among patients with elevated baseline CRP, infliximab
      treated patients improved significantly compared with placebo-treated patients in
      percent-predicted FVC (+2.5 versus -2.6%), 6MWD (+8.0 versus -34.1), Borg's CR10
      dyspnea score (pre-6MWD -0.8 versus +0.9, post-6MWD -1.1 versus +0.8), and POA (
      3.1 versus -0.3). Patients with lower CRP levels at baseline did not show
      significant differences between the placebo and infliximab groups in most
      endpoints evaluated. CONCLUSIONS: In chronic sarcoidosis patients, elevated CRP
      appears to identify a subset with more severe disease who may respond better to
      treatment with infliximab.

PMID- 21086906
TI  - Cathepsin-K is a sensitive immunohistochemical marker for detection of micro
      granulomas in hypersensitivity pneumonitis.
AB  - Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that occurs
      upon exposure to a variety of inhaled organic antigens. The presence of small non
      caseating granulomas and isolated giant cells is not specific, but is considered
      a relevant histological feature for HP. The detection of granulomas is widely
      considered as easy on standard histological stains, but microgranuloma detection
      can be difficult and/or time consuming, especially in chronic HP cases. Cathepsin
      K (Cath-K) is a potent cysteine protease expressed at high levels in activated
      macrophages (osteoclasts, and epithelioid cells in granulomas), but is not
      expressed in resident macrophages thus representing a promising marker to rapidly
      detect and quantitatively evaluate microgranulomas in interstitial lung diseases.
      We analyzed the expression of Cath-K by immunohistochemistry in 22 subacute and
      chronic HP cases, using semi-quantitative scores. Control samples included normal
      lung tissue, and a variety of interstitial lung diseases: 3 Wegener's
      granulomatosis, 3 sarcoidosis, 3 tuberculosis, 1 berylliosis, 20 idiopathic
      pulmonary fibrosis (IPF), 2 Langerhans' cell histiocytosis, 5 nonspecific
      interstitial pneumonia (NSIP), 5 cryptogenic organising-pneumonia (COP), 2 Airway
      Centered Interstitial Fibrosis (ACIF), 5 desquamative interstitial pneumonia
      (DIP), 3 respiratory bronchiolitis interstitial lung disease (RB-ILD). Intense
      expression of Cath-K was demonstrated in epithelioid and giant cells in all cases
      containing granulomas (HP, sarcoidosis, Wegener's granulomatosis, berylliosis,
      tuberculosis). Among HP cases 19/22 (86.3%) contained granulomas that could be
      semiquantitatively evaluated. In all HP and control cases alveolar macrophages
      did not express Cath-K, including cases characterised by large collections of
      alveolar macrophages such as DIP and RB-ILD. CONCLUSIONS: Cath-K represents a
      sensitive and specific marker to detect and quantitate granulomatous reactions in
      interstitial lung diseases, and is particularly useful in chronic HP cases.

PMID- 21086907
TI  - CD24 gene exon 2 dimorphism does not affect disease susceptibility in Japanese
      sarcoidosis patients.
AB  - BACKGROUND: CD24 proteins are expressed on several inflammatory cells, and play
      an important role for the T-cell activation. OBJECTIVES: The aim of this study is
      to investigate the relationship of a CD24 gene polymorphism to disease
      susceptibility or clinical findings including bronchoalveolar lavage (BAL) cell
      profiles in Japanese sarcoidosis patients. METHODS: A previously reported
      functional single nucleotide polymorphism (SNP) of CD24 gene exon 2 was examined
      in 186 Japanese sarcoidosis patients and 146 sex and age-matched healthy controls
      using restriction fragment length polymorphism method. The distribution of
      genotypes was compared between the two groups. The association between genotypes
      or alleles and clinical features or BAL cell profiles was also examined. RESULTS:
      There were no significant differences in the distribution of genotypes or allele
      frequencies between sarcoidosis and controls. There were also no significant
      differences in clinical features or BAL cell profiles among patients with
      different genotypes of CD24. CONCLUSIONS: There was no relationship between a
      CD24 exon 2 SNP and disease susceptibility or clinical findings in Japanese
      sarcoidosis patients.

PMID- 21086908
TI  - Cytokine gene polymorphisms in sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a disease characterized by granuloma formation in many
      organs, but mostly in lung and lymph nodes. The immunopathogenic background of
      the disease is probably based on disregulation of immune response to different
      antigens. The imbalance of immune reactivity might be influenced by genetic
      background. In our study, we have investigated cytokine genetic polymorphisms in
      sarcoidosis group and compared the results with that of a group of healthy
      volunteers. METHODS: Thirty one sarcoidosis patients were enrolled to our study.
      Basic demographic data were collected. Polymorphisms in the promoter regions of
      the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, TNF
      alpha, IFN-gamma and in the translated regions of the TGF-beta, IL-1 beta, IL-2,
      IL-4 and IL-4RA genes were characterized. RESULTS: For IL-10, the (-819) and (
      592) CC homozygosity was statistically more frequent in the sarcoidosis group
      compared to healthy controls. According to the haplotypes, the majority of
      sarcoidosis patients had IL-10 (-1082)(-819)(-592) ACC haplotype 2 compared to
      controls with ATA in most of the cases. CONCLUSIONS: The results of our study
      support the hypothesis of a genetically encoded immune regulation imbalance in
      sarcoidosis. The high-producer IL-10 (-819) and (-592) CC genotypes and
      intermediate- producer IL-10 (-1082) (-819) (-592) ACC haplotype 2 present in the
      majority of our sarcoidosis patients could support the role of genetically
      encoded disregulation of cell- mediated immune response to an unknown antigen.

PMID- 21086910
TI  - Presidential papers.

PMID- 21086909
TI  - Massive pleural effusion and bronchopleural fistula in Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is characterized by systemic granulomatous
      necrotizing vasculitis, primarily affecting the respiratory tract and kidneys. We
      describe a rare case in a 28-year-old woman with WG, presenting with a massive
      lateral pleural effusion, accompanied by an aseptic bronchopleural fistula formed
      during immunosuppressive treatment. Although any organ can be involved in WG,
      only left pleuritis and a purpuric lesion on the neck were detected in this case.
      The pleural effusion and bronchopleural fistula resolved following
      immunosuppressive treatment for six months. Thus, WG should be considered in the
      differential diagnosis of a massive pleural effusion, and fistula formation is a
      possible complication of treatment. Moreover, immunosuppressive treatment was
      sufficient to resolve the massive pleural effusion and fistula formation without
      infection (120 words).

PMID- 21086911
TI  - Let's all share the wealth.

PMID- 21086912
TI  - Concept of the Global Oral Health Initiative: a project of the Alpha Omega
      International Dental Fraternity.

PMID- 21086913
TI  - Global Oral Health Task Force.

PMID- 21086914
TI  - Abayudaya update.

PMID- 21086915
TI  - DVI: vision, commitment, and future.

PMID- 21086916
TI  - Dentist's work routine includes regular volunteer time in Jerusalem and Chicago.

PMID- 21086917
TI  - Tomorrow's SMILES: helping prepare teens for success.

PMID- 21086918
TI  - Alpha Omega in Riga, Latvia.

PMID- 21086919
TI  - Volunteering in Guatemala, AO style.

PMID- 21086920
TI  - Special Olympics Special Smiles: the Detroit Alumni Chapter perspective.

PMID- 21086921
TI  - Report on the Jewish Immigrant Assistance Service Dental Clinic.

PMID- 21086922
TI  - Dental reflections from Ethiopia.

PMID- 21086923
TI  - On learning and giving: a voluntary community project.

PMID- 21086924
TI  - Message from the head of the School.

PMID- 21086925
TI  - A complex cyst characterized into its individual components: a shared
      pathogenesis from the superior tibiofibular joint.
AB  - In a patient with a peroneal neuropathy, magnetic resonance imaging (MRI) allowed
      characterization of a complex para-articular cyst into three different types of
      cysts, all derived from the superior tibiofibular joint: 1) an intraneural cyst
      extending along the articular branch to the common peroneal nerve; an
      interconnected intraneural component extending within the extensor digitorum
      muscle neural branch, penetrating the fascia of the anterior compartment, and
      reaching the subcutaneous tissues; 2) an intraosseous cyst isolated to the
      fibular head and neck, and 3) an extraneural cyst heading toward the tibial nerve
      and vessels. Joint resection and articular branch disconnection led to excellent
      functional recovery; an MRI confirmed no cyst recurrence. This case illustrates
      that different types of cysts can derive from a single joint of origin and extend
      in various locations and that the articular (synovial) theory is versatile for
      demonstrating a joint connection, even in unusual appearing combinations of
      cysts.

PMID- 21086926
TI  - Traumatic closed transection of the triceps brachii: a case report.
AB  - There are only a few reports about intramuscular injury to the triceps brachii,
      offering the surgeon limited clinical options and estimates of prognosis. This is
      a case report of a patient with a traumatic closed tear of his triceps brachii
      who was treated surgically. This report presents the initial surgical management
      and data throughout 64 months of follow-up, during which time the patient showed
      continual, gradual improvement in function with no functional limitations.

PMID- 21086927
TI  - Noninstrumented facet fusion in patients undergoing lumbar laminectomy for
      degenerative spondylolisthesis.
AB  - The purpose of this retrospective study was to evaluate the radiographic and
      clinical efficacy of uninstrumented facet fusion in elderly patients undergoing
      lumbar laminectomy for spinal stenosis due to a single-level degenerative
      spondylolisthesis. Several studies have clearly demonstrated the beneficial
      effects of concomitant spinal fusion with laminectomy in degenerative
      spondylolisthesis. Controversy, however, persists regarding the virtues of fusion
      in this patient population. This study included 62 patients with a single-level
      grade I or II degenerative spondylolisthesis who underwent laminectomy and
      uninstrumented facet fusion for unremitting symptoms of spinal stenosis. Group 1
      (39 patients) had a fixed degenerative spondylolisthesis with no measurable
      translation on flexion/extension radiographs, while group 2 (23 patients) had a
      mobile degenerative spondylolisthesis with preoperative translation.
      Postoperatively, the 62 listhetic levels were analyzed for radiographic signs of
      instability on flexion/extension radiographs for a minimum of 24 months. Clinical
      outcome was assessed in each patient at the time of final follow-up. In group 1
      (patients with no preoperative translation), 64% of the index listhetic facet
      fusion levels had < or = 2 mm of motion on postoperative flexion/extension
      radiographs, while the other 36% had > 2 mm to < or = 15 mm of motion. Ninety-six
      percent of patients with < or = 2 mm of postoperative motion were "much better"
      after surgery, whereas only 50% of patients with > 10 mm of postoperative motion
      had similar results. Similar trends were also observed in group 2 with 52% of
      levels having < or = 2 mm motion and patient "much better" outcomes being
      observed with less motion postoperatively. The overall postoperative radiographic
      stabilization rate and improved patient outcomes were higher in group 1 than in
      group 2. In patients undergoing laminectomy for a grade I or II fixed or mobile
      degenerative spondylolisthesis, concomitant facet fusion decreases motion and
      stabilizes the spine via a bony fusion or a stable pseudarthrosis. In general,
      patients with less motion on postoperative flexion/extension radiographs had a
      better clinical outcome than those with more motion.

PMID- 21086928
TI  - Utility of magnetic resonance imaging obtained before evaluation by the hand
      surgeon.
AB  - The objective of this study was to assess prospectively the utility of magnetic
      resonance imaging (MRI) obtained before evaluation by a hand surgeon. Over a 4
      week period, the hand surgeon documented the type of imaging used in each
      encounter, which prereferral MRIs were useful, and if he agreed with the
      radiologist's interpretation. Of 396 consecutive patients, 14 (4%) presented with
      an MRI. Of those MRIs, 10 were found to be useful. The hand surgeons agreed with
      the radiologist's interpretation on 13 of the 14. Eleven patients presented with
      only an MRI, and 10 of those were helpful. In contrast, none (0 of 3) of the MRIs
      of patients who presented with both radiographs and an MRI were useful (p = .01).
      These results suggest that previous retrospective studies may be confounded by
      recall bias. The data support the selective ordering of MRIs by referring
      physicians; however, ordering more than one imaging modality is less likely to be
      helpful.

PMID- 21086929
TI  - Beta-blocker prophylaxis for total knee arthroplasty patients: a case series.
AB  - Cardiac complications are an infrequent yet undesirable cause of morbidity and
      mortality following total knee arthroplasty. Perioperative prophylaxis with beta
      blocker medication has been shown to reduce in-hospital cardiac deaths in
      noncardiac surgical patients. This study evaluated the safety and in-hospital
      cardiac complications of a consecutive cohort of 267 total knee arthroplasties in
      patients who followed a perioperative beta-blocker prophylaxis institutional
      protocol. The patients were categorized into three groups: A, already on a beta
      blocker; B, beta-blocker prescribed by orthopaedic surgeon; and C, not given the
      medication. The 90-day mortality and in-hospital cardiac complications were
      evaluated. Of the patients who had 267 procedures, 203 (76%) received beta
      blocker prophylaxis perioperatively: 110 (41.2%) were already on the medication
      preoperatively, 93 (34.8%) were prescribed the medication by the surgeon, and 64
      (24%) did not receive this medication. There were no deaths within the first 90
      days. There were two nonfatal myocardial infarctions (0.7%) and six other cardiac
      complications (2.2%). With a beta-blocker prophylaxis protocol implemented by one
      surgeon, 76% of total knee arthroplasty patients were given the medication and it
      was prescribed in 34.8% by the orthopaedic surgeon. In-hospital cardiac
      complications were low.

PMID- 21086930
TI  - Effectiveness of the cavus foot orthosis.
AB  - This study investigated the use of a custom cavus foot orthosis (CFO) in the
      treatment of ankle instability and pain associated with the subtle cavus foot, a
      common pathological foot alignment in the United States population. Patients
      referred by a single orthopedic foot and ankle surgeon to a single pedorthotist
      for a CFO over a 2-year period were eligible. Pain score pre-and postorthosis and
      number of instability events pre- and postorthosis were retrospectively
      evaluated. Ninety-three of 174 eligible patients participated. Average age was 48
      years (range, 20-75) and patients suffered a variety of foot pathologies. Average
      pre-CFO pain score was 7.22 (0 no pain, 10 worst pain). Post-CFO pain score
      average was 2.41 (p < .0005). Ninety-two percent of patients reporting ankle
      instability as a problem experienced a decrease in the frequency of instability
      events post-CFO. The custom cavus foot orthosis is effective at relieving pain
      and reducing ankle instability in the patient with the subtle cavus foot
      alignment.

PMID- 21086931
TI  - The effect of footwear on preoperative gait mechanics in a group of total ankle
      replacement patients.
AB  - Debate exists within the current clinical literature as to whether patients
      should be tested barefoot or in shoes either before or following surgical
      interventions. The objective of this study was to determine the effect of shod
      versus barefoot walking on spatiotemporal gait parameters before total ankle
      arthroplasty (TAA). Twenty patients who were scheduled for TAA were asked to walk
      four trials in shoes and four barefoot trials over a GaitRite mat while
      spatiotemporal variables were recorded. A series of repeated measures analysis of
      variance were performed to determine significant differences (alpha = 0.05). Step
      length, stride length, double support time, and walking velocity were
      significantly increased in the shod condition. However, step width, swing time,
      and support time were significantly decreased in the shod condition. The results
      of this study indicate the importance of testing clinical populations barefoot in
      order to more accurately assess gait pathology.

PMID- 21086932
TI  - Infection rate and risk factor analysis in an orthopaedic ambulatory surgical
      center.
AB  - Surgical site infections (SSI) are a costly problem. The purpose of this study
      was to determine the rate of infection and identify patient and technical risk
      factors for SSI in an orthopaedic ambulatory surgical center. Over 11,000
      consecutive orthopaedic surgeries over 5 years were reviewed for SSI as well as
      demographic, medical, and surgical risk factors. Nearly 400 noninfected patients
      served as statistical controls. The overall infection rate was 0.33%, which
      compares favorably to previous studies of outpatient surgery and appears to be
      substantially lower than SSI rates previously reported for inpatient orthopaedic
      surgery. Male sex, smoking, and diabetes demonstrated significantly higher risk
      for infection. Surgery time and duration of anesthesia administration were also
      associated statistically with SSI. A history of cancer, hypertension, or thyroid
      problems were all associated with higher but statistically insignificant risk of
      SSI. Patient age and number of past surgeries were equal in the SSI and control
      groups.

PMID- 21086933
TI  - Clinical observations on surgical details of resection of heterotopic
      ossification at the hip in traumatic brain-injured adult.
AB  - Heterotopic ossification (HO) complicated with neurovascular bundle can be a very
      challenging operation. Preoperative planning before any HO resection is
      imperative. Plans to reconstruct nerve or artery should be in place. A case study
      is presented that involved a large bone mass of HO in hip joint which enclosed
      the sciatic nerve. Preoperative planning, microsurgical techniques, and equipment
      necessary for this complicated surgical procedure are reviewed.

PMID- 21086934
TI  - Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in
      clinical practice in patients with inflammatory bowel diseases.
AB  - Thiopurines (TP) are widely used in the management of inflammatory bowel
      diseases. Side-effects and inefficacy are a major concern as they lead to
      withdrawal of the drug. Tools investigating TP metabolism are useful to avoid
      inadequate cessation of TP therapy. TP metabolism is complex and many enzymes are
      involved. Among them, Thiopurine methyltransferase (TPMT) is the only one
      routinely measured by pheno- or genotyping. In this review, the rationale for
      TPMT and thiopurine metabolites, 6-thioguanine nucleotides and 6
      methylmercaptopurine, determination in clinical practice is discussed,
      specifically in case of thiopurine failure and recommendations are given about
      their interpretation and potential dose optimization of TP drugs.

PMID- 21086935
TI  - Covered stents are better than uncovered stents for transjugular intrahepatic
      portosystemic shunts in cirrhotic patients with refractory ascites: a
      retrospective cohort study.
AB  - BACKGROUND AND STUDY AIMS: Transjugular intrahepatic portosystemic shunt (TIPS)
      is an accepted interventional technique to treat refractory ascites in cirrhotic
      patients with severe portal hypertension. The expanded-polytetrafluoroethylene (e
      PTFE) covered stent-graft (cs-TIPS) gives a better shunt patency rate than
      uncovered stents (ncs-TIPS). Our aim was to retrospectively evaluate whether cs
      TIPS indeed improves refractory ascites and overall survival in a more effective
      way than ncs-TIPS in patients with cirrhosis. PATIENTS AND METHODS: From 1992 to
      2006, 222 cirrhotic patients with refractory ascites underwent a TIPS-procedure.
      In 126 patients a ncs-TIPS was inserted, in the remaining 96 patients a csTIPS
      was inserted. Liver transplantation and/or death were the end points of the
      follow-up. RESULTS: The baseline characteristics of both groups were similar: age
      (55 +/- 11 years, ncs-TIPS/56 +/- 10 years, cs-TIPS), alcoholic cirrhosis (73%
      ncs-TIPS/80% cs-TIPS), Child-Pugh (9 +/- 2.0 ncs-TIPS/9.2 +/- 1.3 cs-TIPS) and
      MELD (15 +/- 6 ncs-TIPS/15 +/- 4.9 cs-TIPS), except that the bilirubin level was
      higher in the cs-TIPS group (2.5 +/- 2.7 mg/dL in cs-TIPS vs. 1.5 +/- 3.6 mg/dL
      in ncs-TIPS). One year shunt dysfunction occurred in 49% (n=63) of the ncs-TIPS
      vs. 19% (n = 18) of the cs-TIPS (P < 0.0001) and post TIPS encephalopathy in 56%
      (n=70) of the ncs-TIPS vs. 22% (n = 22) in the cs-TIPS group. Ascites control and
      overall survival were better in the cs-TIPS (P = 0.0071). The gain in survival in
      the cs-TIPS patients occurred especially in patients with a baseline MELD score
      <16 (P < 0.0001). Post TIPS encephalopathy and ncs-TIPS were independently
      related with poor survival (P < 0.0001, P = 0.0150; respectively). CONCLUSIONS:
      In cirrhotic patients with refractory ascites cs-TIPS offers better symptomatic
      control of the ascites at one year follow-up and a better overall survival,
      especially in patients with a MELD score of <16 at baseline.

PMID- 21086936
TI  - Biological agents in paediatric inflammatory bowel disease: a clinical
      observation study from Greece.
AB  - OBJECTIVES: Biological agents have contributed significantly in controlling
      inflammatory bowel disease during the last 15 years. This study aimed at
      recording and evaluating paediatric data regarding the efficacy and safety of
      infliximab and adalimumab during the last decade. PATIENTS AND METHODS: A total
      of 31 patients (43% males) with a mean age of 13.5 +/- 3.0 years were included
      and the majority (74%) had Crohn's disease (CD). Failure of previous treatment
      and steroid dependency were the main reasons for initiating anti-TNF-alpha
      therapy. Mean age at the first infusion was 11.0 +/- 2.8 years, while the mean
      disease duration at the introduction of infliximab was 2.6 +/- 2.7 years. The
      number of infusions per patient ranged from 1-25 (median 7, IQR: 4-13). RESULTS:
      Initial response was achieved in 82.8% of patients. After one year of treatment
      the estimated rate of remission was 53%. The rate of surgery-free disease at 12,
      36 and 60 months, after the first dose of infliximab, was 89.6%, 89.6% and 74.7%
      respectively. The incidence of serious anaphylaxis was 4/268 infusions (1.5%) or
      4/31 patients (12.3%). At three months after the first infusion only 2 children
      were on steroids. Adalimumab was administered to 5 patients for a mean duration
      of 7.4 months, as a second option after infliximab failure or infusion reaction.
      Two out of five patients failed to achieve remission with adalimumab and these
      two patients were also infliximab failures. CONCLUSION: Biological agents are
      valuable and safe options for children with refractory IBD. The results, so far,
      have been satisfactory, although, long-term outcomes remain yet to be determined.

PMID- 21086937
TI  - Gastrointestinal stromal tumors: review on morphology, molecular pathology,
      diagnostics, prognosis and treatment options.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common non-epithelial
      mesenchymal tumors of the gastrointestinal tract. GISTs represent a specific
      group of mesenchymal tumors with uncertain biological behaviors. These tumors are
      assumed to originate from progenitor cells, usually unable to self-regenerate,
      which differentiate towards Cajal cells. Apart from common GISTs that occur
      predominantly in adulthood, a heterogeneous group of tumors has been described
      that are morphologically identical with GIST, but have a specific clinical
      presentation and biological properties. Approximately 30% of newly diagnosed
      GISTs are malignant or have a high potential for malignancy. Currently, GISTs are
      routinely identified with histological, immunohistochemical, and molecular
      genetic assays. However, clinical diagnoses, particularly of small or intramural
      GISTs, might be difficult. The most useful techniques for imaging and monitoring
      disease progression are endoscopic examinations and fused PET/CT imaging.
      Surgical treatment is the first-line treatment and the only method that might
      lead to full remission in patients with a primary GIST. There is currently no
      consensus on the issues of whether to perform resections in patients with
      positive margins or resections of metastases. Endoscopic resection could
      represent a relatively simple and less aggressive alternative as compared to
      traditional surgery in the treatment of small sized GISTs. Biological therapy
      with imatinib mesylate is recommended for patients with newly diagnosed, locally
      advanced, inoperable, or metastasizing gastrointestinal GISTs that express the c
      KIT protein. Treatment may reduce a primary tumor to a size small enough for
      surgical excision. Current research is focusing on the development of new
      therapies for the treatment of advanced disease and/or disease prophylaxis.

PMID- 21086938
TI  - Functional dyspepsia: still a serious challenge for medical practitioners and new
      drug investigators? A Belgian, French, German and Hungarian opinion.
AB  - The diagnosis of Functional Dyspepsia is based on the identification of long term
      specific symptoms and the absence of organic lesions. Many pathophysiological
      mechanisms are intricate and, at least, partially responsible for the syndrome.
      Widely accepted technical procedures for the identification of these mechanisms
      are missing. The final etiopathology is not yet established. The relationship
      between symptoms and putative mechanisms is unclear. At the moment of the
      prescription, the physician faces a real therapeutic gap. Moreover, Functional
      Dyspepsia is an evolving area of study and knowledge has to be updated regularly.
      As a result, consultations for Functional Dyspepsia are usually very challenging
      and patients look desperately for medical support. It is likely that this disease
      is both under-diagnosed and under-treated. Classifying patients into symptomatic
      subgroups is a promising approach proposed by Rome III. It is assumed that these
      subgroups are based on different pathophysiological mechanisms, and may allow for
      more specific therapeutic approaches. However the assessment of the symptomatic
      profiles of patients is time-consuming. It is also a risky process, because the
      Rome III subgroups have yet to be validated. There are currently no translations
      of the definitions in the different European languages. Interviews of the
      patients are biased by cultural, educational and subjective factors.
      Identification of suitable subjects for clinical trials is uneasy for the same
      reasons and can explain several recent Research and Development (R&D) failures.
      Therefore, there is a need for an updated, step by step approach, a real
      diagnostic algorithm of the consultation including the use of simple, clear,
      universal and cross-cultural validated tools, as word-figure questionnaires,
      designed to establish the symptomatic profiles of the patients.

PMID- 21086940
TI  - The ministransplant procedure in liver transplantation.
AB  - In order to ameliorate early recovery after liver transplantation a reduction of
      invasiveness of the abdominal incision has been tested and compared with more
      extended incisions. This approach named "minitransplant procedure" resulted in
      better early and late outcome results irrespective of preoperative patients' risk
      factors as previous upper abdominal surgery, Body Mass Index and Model of End
      Stage Liver Disease score.

PMID- 21086941
TI  - The compromised arterial tree: how to deal with?
AB  - It is accepted that for achieving a successful liver transplantation one of the
      most important points is the arterial revascularization of the graft. Sometimes
      the recipient's hepatic artery is not suitable for anastomosis. In this review,
      we will discuss the different options to deal with a compromised arterial tree in
      cadaveric orthotopic liver transplantation with whole graft.

PMID- 21086942
TI  - Alternative transplant procedures for acute liver failure.
AB  - Acute liver failure (ALF) is associated with significant morbidity and mortality.
      The outcome is highly unpredictable and recovery depends on several factors.
      Patients can deteriorate with increasing encephalopathy, coagulopathy and
      progress to multiorgan failure (MOF). In such patients, liver transplantation
      (LT) is the only current potential cure. Orthotopic liver transplantation remains
      the standard procedure for LT in ALF, however, other surgical options have been
      explored. This review summarises the use of a variety of alternative transplant
      procures for the treatment of acute liver failure including: Two stage OLT,
      Auxiliary liver transplant, Living donor liver transplantation (LDLT), and ABO
      incompatible liver transplant.

PMID- 21086943
TI  - Liver transplantation in HIV infected patients: indications and results.
AB  - Liver transplantation (LT) is now feasible in HIV infected patients. To date,
      criteria of liver transplantation are no different from the other indications of
      liver transplantation; however an undetectable HIV viral load at the time of
      liver transplantation is desirable goal. History of opportunistic infections and
      CD4+ count < 100/mL do not constitute exclusion criteria. Long-term outcomes for
      HBV/HIV are excellent. Outcomes for HCV/HIV coinfected patients are more variable
      because of potentially severe recurrence on the liver graft. More effective
      antiviral therapy at an early stage post LT is required.

PMID- 21086944
TI  - Psychological evaluation of living liver donors--a single centre experience.
AB  - The psychological evaluation of living liver donors is a substantial part of the
      preoperative evaluation of donors in many transplantation centres around the
      globe and aims at securing decision autonomy and informed consent, verifying the
      psychological stability of the donor and ruling out psychosocial risks. The aims
      of this paper are to present a short overview of the current state of the
      psychosocial evaluation of living donors based on the existing literature and to
      discuss our centre's experience in the psychological evaluation of donors, the
      lessons we have learned in the past 10 years and an agenda for the future
      evaluation of donors and research.

PMID- 21086945
TI  - Seroconversion of acute hepatitis B by antiretroviral therapy in an HIV-1
      infected patient.
AB  - A 33-year-old man with human immunodeficiency virus type1 (HIV-1) infection was
      admitted because of acute hepatitis B. His serum alanine aminotransferase level
      was 1200 IU/mL and CD4 cells count was 268/mm3. Antiretroviral therapy including
      tenofovir and emtricitabine, which suppresses both HIV and hepatitis B virus
      (HBV) replication, was initiated. The liver enzymes decreased dramatically. The
      viral loads of both HIV-1 and HBV were suppressed below detectable limits.
      Seroconversion from hepatitis B surface antigen to hepatitis B surface antibody
      was acquired 19 weeks later. In this case, the initiation of antiretroviral
      therapy with anti-HBV activity during the acute phase of hepatitis B had a
      favourable effect on HBV serostatus.

PMID- 21086946
TI  - Whipple's disease. A classic case report and review of the literature.
AB  - We report the case of a 43-year-old carpenter with abdominal complaints and
      progressive weight loss. The HLA-B27 positive male had been suffering migratory
      arthropathy for five years, only partially under control with corticosteroids and
      methotrexate therapy. Endoscopic investigation showed dark staining of the
      duodenal mucosa and the ileal mucosa had an erythematous aspect with multiple
      white spots. Abundant periodic acid Schiff positive macrophages were seen on
      histologic examination of biopsy samples. This is a classic presentation of
      Whipple's disease, a rare multisystemic disease caused by the Tropheryma
      whipplei. Typical symptoms are arthropathy, weight loss, abdominal pain and
      diarrhea, but also systemic and neurological manifestations may occur. The
      otherwise lethal disease can be treated with long term antibiotics.

PMID- 21086948
TI  - Daily cannabis use and the digestive tract: an underrecognized relationship.
AB  - A 33-year-old man presented with recurrent episodes of hyperemesis with symptom
      free intervals since eight years. The diagnosis of cyclic vomiting syndrome due
      to longstanding and daily cannabis use was retained, after exclusion of any
      organic cause of vomiting. Although the patient was informed that the clinical
      response after cessation of smoking is proven to be spectacular, he continued the
      use of cannabis and kept on presenting with cyclic symptoms of hyperemesis.

PMID- 21086947
TI  - Second primary malignancies in patients with a gastrointestinal neuroendocrine
      tumour: a case report and review of the literature.
AB  - A second primary malignancy (SPM) is frequently reported in patients with a
      gastrointestinal neuroendocrine tumour (NET). The majority of SPM are located in
      the gastrointestinal tract, but malignancies at other sites are described as
      well. This phenomenon might just be coincidental due to high incidence rates of
      asymptomatic NET lesions in patients who are operated or who undergo autopsy for
      another primary malignancy. However, other theories have been developed since the
      observed incidences rates seem to be double as high as expected. Some authors
      suggest a common genetic predisposition, while others report tumourigenic
      properties of various neuroendocrine peptides, including secretin, gastrin and
      cholecystokinin. This review is illustrated by a case report of a patient in whom
      the radiological diagnosis of a diffuse liver metastasized adenocarcinoma of the
      rectum changed dramatically after positron emission tomography and explorative
      laparoscopy to a curable adenocarcinoma of the rectum with a simultaneous well
      differentiated neuroendocrine carcinoma.

PMID- 21086949
TI  - Endoscopic removal of a bleeding colonic polypoid angiodysplasia: case report.
AB  - Arteriovenous malformations are common causes of lower gastrointestinal bleeding
      in the elderly. Among them, angiodysplasia is one subtype that appears on
      endoscopy as red, flat superficial lesions, and sometimes slightly elevated.
      Colonic angiodysplasia is very rarely seen as a polypoid lesion. The present case
      describes a bleeding large polypoid colonic angiodysplasia in a 60-year-old man.
      It was removed endoscopically using a PolyLoop ligature device without
      complications.

PMID- 21086950
TI  - Giant appendix as result of chronic appendicitis: report of a case.

PMID- 21086951
TI  - Protein-losing enteropathy caused by spontaneous superior mesenteric artery
      dissection with thrombosis.

PMID- 21086953
TI  - Cutaneous metastases from carcinoma of the bile duct.

PMID- 21086952
TI  - A case of intestinal obstruction caused by a peritoneal loose body mimicking
      gallstone ileus.

PMID- 21086954
TI  - Federalism, intergovernmental relations, and the challenge of the medically
      uninsurable: a retrospective on high risk pools in the states.
AB  - While relatively overlooked in health policy research and analysis, state high
      risk insurance pools play a notable role in contemporary health policy
      arrangements. Also know as State Comprehensive Health Insurance Plans, high-risk
      pools emerged in the late 1970s as states began to grapple with the challenges of
      the medically uninsured. Today, thirty-five states operate these programs. To
      further our understanding of health and human services administration, it is
      important to examine these plans, especially in context of intergovernmental
      health policy in the United States. This analysis provides an overview of high
      risk pool evolution and gives attention to forces that have shaped their
      development, such as model legislation, funding arrangements, and increasing
      federal-level interest in their use as platforms to advance national policy
      initiatives.

PMID- 21086955
TI  - The influence of environmental and organizational factors on hospitals' clinical
      IT sophistication.
AB  - The present study examines the separate and combined effects of environmental and
      organizational variables on hospitals' clinical IT sophistication in a
      multivariate framework. The analyses focused on two distinct but related
      questions. First, in the context of the bivariate hypotheses, what is the
      relative significance empirically of each of the environmental and organizational
      classes of variables? And second, within classes and on an overall basis, which
      specific variables make the largest contribution to explained variance in the
      dependent variable hospitals' clinical IT sophistication when all other variables
      are held constant? Data collected from 99 Texas hospitals are analyzed to assess
      the effects of the antecedent variables both within and across classes. Our
      findings suggest the bigger contribution of environmental antecedents to the
      level of clinical IT sophistication in hospitals, compared to that of
      organizational antecedents. We end by discussing the limitations and implications
      of the study.

PMID- 21086956
TI  - Illness onset as status passage for people with multiple sclerosis (MS).
AB  - The lived experience of the Illness Onset Status Passage for people with Multiple
      Sclerosis (MS) is explored here. Glaser and Strauss' (1971) status passage is
      used to analyse the properties of this Status Passage. The Illness Onset Status
      Passage for people with MS includes three key phases: (1) An Unknown Passage
      lived as either what are thought to be "Harmless" Symptoms or, conversely, as
      Alarming Symptoms, both of which are experienced without knowledge of having MS;
      (2) Incomplete Knowledge (ie accompanying initial diagnosis) Lived as Felt Stigma
      arising as a result of the person's own lack of useful knowledge of the disease
      at the point of diagnosis, and compounded by negative community stereotypes about
      MS; and, (3) Living Thrownness, where the person with MS is thrown into turmoil
      and ill equipped to deal with their changed life. While it is acknowledged that
      the life journey for people with MS will contain multiple status passages, this
      initial status passage--the Illness Onset Status Passage--needs to be better
      understood so that people with MS get the support that they need from health care
      professionals and others at such a critical time in their lives.

PMID- 21086957
TI  - Impact of the health services utilization and improvement model (HUIM) on self
      efficacy and satisfaction among a head start population.
AB  - The aim of this paper is to evaluate and report the impact of the Health Services
      Utilization Improvement Model (HUIM) on utilization and satisfaction with care,
      as well as knowledge regarding prevention, detection, and treatment of asthma,
      diabetes, tuberculosis, and child injury among low income health services
      consumers. HUIM outcomes data shows that the coupling of parental education and
      ecological factors (service linkage and provider orientation) impacts the health
      services utilization experience of low income consumers evidenced by improved
      self-efficacy (knowledge and voice), and satisfaction with care from a child's
      regular provider. Participation in HUIM activities also improved the low income
      consumer's knowledge of disease identification, self-care and prevention.

PMID- 21086959
TI  - Synthesis of diverse N,O-bridged calix[1]arene[4]pyridine-C(60) dyads and triads
      and formation of intramolecular self-inclusion complexes.
AB  - Starting from both the bridging nitrogen atom-functionalized and the upper rim
      functionalized N,O-bridged calix[1]arene[4]pyridine reactants, different types of
      heteracalixaromatics-C(60) dyads and triads of varied spacers were expediently
      synthesized using mainly the click reaction as the key step. By means of various
      spectroscopic methods, the heteracalixaromatics-C(60) dyads and triads obtained
      have been shown to form intramolecular self-inclusion complexes rather than
      oligomers or polymers in solution because of a flexible spacer in between the
      heteracalixaromatic ring and C(60) moiety. The current study, coupled with
      previous investigations, would provide the guideline for the construction of
      supramolecular fullerene motifs based on molecular design of the dyads and
      triads.

PMID- 21086958
TI  - CAN-mediated oxidations for the synthesis of xanthones and related products.
AB  - Reaction of (2,4,5-trimethoxyphenyl)(2-hydroxyphenyl)methanone with ceric
      ammonium nitrate furnished the xanthone, 2,3-dimethoxy-9H-xanthen-9-one. Under
      the same conditions the related (1,4-dimethoxynaphthalen-2-yl)(2
      hydroxyphenyl)methanone resulted in the formation of 12a-methoxy-5H
      benzo[c]xanthenes 5,7(12aH)-dione. Other examples of this novel transformation
      are also outlined.

PMID- 21086960
TI  - Uncatalyzed, diastereoselective vinylogous Mukaiyama aldol reactions on aqueous
      media: pyrrole vs furan 2-silyloxy dienes.
AB  - The first uncatalyzed, diastereoselective vinylogous Mukaiyama aldol reaction is
      reported, between pyrrole/furan-based dienoxy silanes and aromatic aldehydes on
      salty water/methanol medium, at almost human body temperature, under ultrasonic
      irradiation. With pyrrole dienes the reaction is anti-selective, while that of
      furan dienes is syn-selective. The dual role of water as both reaction medium and
      promoter is highlighted.

PMID- 21086962
TI  - Weak epitaxy growth of phthalocyanine on 2,5-bis(4-1,1':4',1''-terphenyl)
      thiophene and the effect of phase state of inducing layer.
AB  - The growth of ultrathin films of 2,5-bis(4-1,1':4',1''-terphenyl)-thiophene (3PT)
      and weak epitaxy growth (WEG) behavior of phthalocyanines (H(2)Pc and ZnPc) on
      3PT ultrathin films were investigated by atomic force microscopy, X-ray
      diffraction (XRD), and select area electron diffraction (SAED). Domain size of
      the monolayer films can reach 10 MUm at the substrate temperature of 190  degrees
      C. The second layer films begin to show Volmer-Weber growth mode. This growth
      mode transformed without a concomitant phase transition. The XRD and SAED
      measurements indicate the monolayer and double-layer films of 3PT have identical
      in-plane and out-of-plane structure. The epitaxial ZnPc films have a similar
      orientation or intertexture shape utilizing 3PT monolayer and double-layer films
      as the inducing layer. By comparison with utilizing para-sexiphenyl (p-6P) as the
      inducing layer, the morphology with clear borderline of epitaxial films with
      different orientations on joint of neighboring 3PT monolayer domains disclosed
      that the 3PT monolayer films have characteristics of crystal. Meanwhile the
      distinguishing effects of inducing layer phase state on morphology of epitaxial
      films were shown, respectively.

PMID- 21086961
TI  - Heterogeneities in gelatin film formation using single-sided NMR.
AB  - Gelatin solutions were prepared in D(2)O. The drying process of cast solutions
      was followed with a single-sided nuclear magnetic resonance (NMR) scanner until
      complete solidification occurred. Spin-spin relaxation times (T(2)) were measured
      at different layers with microscopic resolution and were correlated with the
      drying process during film formation. Additionally, the evaporation of the
      gelatin solution was observed optically from the reduction of the sample
      thickness, revealing that at the macroscopic level, the rate of evaporation is
      not uniform throughout the experiment. A crossover in the spatial evolution of
      the drying process is observed from the NMR results. At the early stages, the gel
      appears to be drier in the upper layers near the evaporation front, while this
      tendency is inverted at the later stages, when drying is faster from the bottom.
      XRD (X-ray diffraction) data showed that a structural heterogeneity persists in
      the final film.

PMID- 21086963
TI  - Polarized cluster dynamics at the paraelectric to ferroelectric phase transition
      in BaTiO3.
AB  - The mechanism of the prototype ferroelectric phase transition in BaTiO(3) is a
      matter of intense debate and to a large extent still wrapped in mystery.
      Precursor phenomena in the form of polarized clusters in paraelectric BaTiO(3)
      are by now believed to represent a key step into the ferroelectric phenomenon.
      The determination of a slower dynamics of cluster polarization flipping along
      with a faster order-disorder Ti hopping mode among <111> off-center sites
      suggests coexistence, instead of mutual exclusion, of displacive and order
      disorder types, initially proposed as distinct models. However, no clear picture
      of the transition state has been proposed so far, which is able to provide
      insight into the coexistence of the paraelectric and ferroelectric phenomena.
      Here, by means of a dedicated molecular dynamics approach, we provide a detailed
      atomistic picture of intermediate regions along the transition. Therein,
      different time and length scales coexist as they characterize different portions
      of the same material. From an imbalance of dynamically and more statically
      polarized clusters in this highly inhomogeneous intermediate, a symmetry breaking
      step naturally results. Further, we find that ferroelectric nanodomains may host
      antiferroelectric defects, which appear as an intrinsic feature of the growing
      BaTiO(3) ferroelectric material.

PMID- 21086964
TI  - Relaxation processes in the adsorption of surface layer proteins to lipid
      membranes.
AB  - The present work evaluates the kinetics of the interaction of S-layer protein
      from Lactobacillus brevis with lipid monolayers by measuring the changes in the
      surface pressure as a function of time for different lipid compositions and at
      different lateral compressions. At high surface pressures, or at high cholesterol
      ratios, in which membrane rigidity and surface polarity are increased, the
      kinetics can be described by a pure diffusional process. At low pressures or in
      the absence of cholesterol, the kinetics of protein interaction can be
      interpreted as a consequence of a relaxation process of the membrane structure
      coupled to diffusion. As the less packed monolayers are more hydrated, the
      relaxation processes at low initial surface pressures could be ascribed to
      changes in water organization in the membrane. These observations denote that
      kinetic insertion of proteins can be modulated by components that modify the
      hydration state of the interface.

PMID- 21086965
TI  - Pairwise substitution effects, inter- and intramolecular hydrogen bonds in
      methoxyphenols and dimethoxybenzenes. Thermochemistry, calorimetry, and first
      principles calculations.
AB  - Methoxyphenols are the structural fragments of different antioxidants and
      biologically active molecules, which are able to form strong intermolecular and
      intramolecular hydrogen bonds in condensed matter. In the present work,
      thermochemical, Fourier transform infrared (FTIR)-spectroscopic and quantum
      chemical studies of methoxyphenols and its H-bonded complexes in solution and gas
      phase have been carried out. Thermodynamic properties (standard molar enthalpies
      of formation, vapor pressure, vaporization enthalpies, sublimation enthalpies,
      and fusion enthalpies) of 2-methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, 1,2
      dimethoxybenzene, 1,3-dimethoxybenzene, and 1,4-dimethoxybenzene have been
      studied in this work. To verify the experimental data, ab initio calculations of
      all compounds have been performed using density functional theory (DFT), MP2, and
      G3 methods. The quantitative analysis of ortho, meta, and para pairwise
      substituent effects in methoxyphenols has been performed. Solution enthalpies of
      methoxyphenols at infinite dilution in proton acceptor solvents have been
      measured. Calorimetric data shows that intermolecular hydrogen bond strength in
      complexes of 2-methoxyphenol with organic bases is less than that for 4
      methoxyphenol. Two experimental approaches for determination of enthalpy of
      intramolecular hydrogen bonds in ortho-methoxyphenols were proposed. The new
      results help to resolve uncertainties in the available thermochemical data on
      methoxyphenols and dimethoxybenzenes and to realize relations among properties
      and structures for these compounds.

PMID- 21086966
TI  - Mo(CO)(6)-mediated carbamoylation of aryl halides.
AB  - A simple method for the synthesis of amides has been developed by molybdenum
      mediated carbamoylation of aryl halides. Whereas the conventional palladium
      catalyzed three-component coupling reaction requires a large excess of gaseous
      carbon monoxide, the incorporation of carbon monoxide in this Mo-mediated
      carbamoylation reaction is so efficient that it requires only a slight excess
      amount of carbon monoxide in the form of its molybdenum complex, Mo(CO)(6). The
      reaction is applicable for the synthesis of a wide variety of not only secondary
      and tertiary amides but also primary amides by using aqueous ammonia.

PMID- 21086967
TI  - Molecular simulations on the thermal stabilization of DNA by hyperthermophilic
      chromatin protein Sac7d, and associated conformational transitions.
AB  - Sac7d belongs to a family of chromosomal proteins, which are crucial for thermal
      stabilization of DNA at higher growth temperatures. It is capable of binding DNA
      nonspecifically, and is responsible for the increase in the melting temperature
      of DNA in the bound form up to 85  degrees C. Molecular dynamics (MD) simulations
      were performed at different temperatures on two protein-DNA complexes of Sac7d.
      Various structural and energetic parameters were calculated to examine the DNA
      stability and to investigate the conformational changes in DNA and the protein
      DNA interactions. Room temperature simulations indicated very good agreement with
      the experimental structures. The protein structure is nearly unchanged at both
      300 and 360 K, and only up to five base pairs of the DNA are stabilized by Sac7d
      at 360 K. However, the MD simulations on DNA alone systems show that they lose
      their helical structures at 360 K further supporting the role of Sac7d in
      stabilizing the oligomers. At higher temperatures (420 and 480 K), DNA undergoes
      denaturation in the presence and the absence of the protein. The DNA molecules
      were found to undergo B- to A-form transitions consistent with experimental
      studies, and the extent of these transitions are examined in detail. The extent
      of sampling B- and A-form regions was found to show temperature and sequence
      dependence. Multiple MD simulations yielded similar results validating the
      proposed model. Interaction energy calculations corresponding to protein-DNA
      binding indicates major contribution due to DNA backbone, explaining the
      nonspecific interactions of Sac7d.

PMID- 21086968
TI  - Free energy landscape for glucose condensation reactions.
AB  - Ab initio molecular dynamics and metadynamics simulations were used to determine
      the free energy surfaces (FES) for the acid catalyzed beta-D-glucose condensation
      reaction. Protonation of C1-OH on the beta-D-glucose, breakage of the C1-O1 bond,
      and the formation of C1 carbocation is the rate-limiting step. The effects of
      solvent on the reaction were investigated by determining the FES both in the
      absence and presence of solvent water. It was found that water played a critical
      role in these reactions. The reaction barrier for the proton-catalyzed glucose
      condensation reaction is solvent induced because of proton's high affinity for
      water. During these simulations, beta-D-glucose conversion to alpha-d-glucose
      process via the C1 carbocation was also observed. The associated free energy
      change and activation barrier for this reaction were determined.

PMID- 21086969
TI  - Pitfalls in assessing the alpha-effect: reactions of substituted phenyl
      methanesulfonates with HOO(-), OH(-), and substituted phenoxides in H(2)O.
AB  - Toward resolving the current controversy regarding the validity of the alpha
      effect, we have examined the reactions of Y-substituted phenyl methanesulfonates
      1a-1l with HOO(-), OH(-), and Z-substituted phenoxides in the gas phase versus
      solution (H(2)O). Criteria examined in this work are the following: (1) Bronsted
      type and Hammett plots for reactions with HOO(-)and OH(-), (2) comparison of
      beta(lg) values reported previously for the reactions of Y-substituted phenyl
      benzenesulfonates 2a-2k with HOO(-) (beta(lg) = -0.73) and OH(-) (beta(lg) = 
      0.55), and for those of 1a-1l with HOO(-) (beta(lg) = -0.69) and OH(-) (beta(lg)
      = -1.35), and (3) Bronsted-type plot showing extreme deviation of OH(-) for
      reactions of 2,4-dintrophenyl methanesulfonate 1a with aryloxides, HOO(-), and
      OH(-), signifying extreme solvation vs different mechanisms. The results reveal
      significant pitfalls in assessing the validity of current interpretations of the
      alpha-effect. The extreme negative deviation by OH(-) must be due, in part, to
      the difference in their reaction mechanisms. Thus, the apparent dependence of the
      alpha-effect on leaving-group basicity found in this study has no significant
      meaning due to the difference in operating mechanisms. The current results argue
      in favor of a further criterion, i.e., a consistency in mechanism for the alpha
      nucleophiles and normal nucleophiles.

PMID- 21086970
TI  - Density functional steric analysis of linear and branched alkanes.
AB  - Branched alkane hydrocarbons are thermodynamically more stable than straight
      chain linear alkanes. This thermodynamic stability is also manifest in alkane
      bond separation energies. To understand the physical differences between branched
      and linear alkanes, we have utilized a novel density functional theory (DFT)
      definition of steric energy based on the Weizacker kinetic energy. Using the M06
      2X functional, the total DFT energy was partitioned into a steric energy term
      (E(s)[rho]), an electrostatic energy term (E(e)[rho]), and a fermionic quantum
      energy term (E(q)[rho]). This analysis revealed that branched alkanes have less
      (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of
      branched alkanes is mitigated by an equal and opposite quantum energy term that
      contains the Pauli component of the kinetic energy and exchange-correlation
      energy. Because the steric and quantum energy terms cancel, this leaves the
      electrostatic energy term that favors alkane branching. Electrostatic effects,
      combined with correlation energy, explains why branched alkanes are more stable
      than linear alkanes.

PMID- 21086971
TI  - Reduction of mercury(II) by the carbon dioxide radical anion: a theoretical and
      experimental investigation.
AB  - The laser flash photolysis technique (lambda(exc) = 266 nm) was used to
      investigate the mechanism of the HgCl(2) reduction mediated by CO(2)(.-) radicals
      in the temperature range 291.7-308.0 K. For this purpose, the CO(2)(.-) radicals
      were generated by scavenging of sulfate radicals by formic acid. The absorbance
      of the reduced radical of methyl viologen, a competitive scavenger of CO(2)(.-),
      was monitored at 390 nm. Moreover, theoretical calculations, including solvent
      effects, were also performed within the framework of the density functional
      theory for various chemical species of Hg(I) and Hg(II) to aid in the modeling of
      the reaction of reduction of HgCl(2) by CO(2)(.-).

PMID- 21086972
TI  - Theoretical and experimental insights into the mechanism of the nucleophilic
      addition of water and methanol to dicyanonitrosomethanide.
AB  - In this work the nucleophilic addition of water and methanol to the
      dicyanonitrosomethanide anion (dcnm, [C(CN)(2)(NO)](-)) in the absence of the
      usual transition metal promoters was investigated. Experimentally it was shown
      that a quantitative conversion of the dcnm anion to
      carbamoylcyanonitrosomethanide (ccnm, [C(CN)(CONH(2))(NO)](-)) by the addition of
      1 equiv of water to a nitrile group is complete in 48 h at 100  degrees C, or in
      1.5 h at 150  degrees C when the reaction is conducted in a microwave reactor.
      Attempts to add a second equivalent of water to the anion failed with thermal
      degradation of the anion occurring at 200  degrees C. Ab initio calculations show
      that the reaction proceeds via three distinct transition states: (1) the transfer
      of a proton from a water molecule to the nitrile group, (2) the subsequent attack
      of the generated hydroxide anion on the carbon atom of the nitrile group, and (3)
      a rapid proton transfer to form a carbamoyl group. The attacking water molecule
      is shown to be a stronger proton donor when modeled as part of a hydrogen-bonded
      three water molecule chain, leading to a significant reduction in the reaction
      barrier. Only the anti-ccnm anion is formed in the reaction. There is a high
      energy barrier to the formation of the syn isomer by the rotation of the nitroso
      group. While the syn isomer of ccnm is shown to be the more thermodynamically
      stable conformation, examination of the HOMO-1 molecular orbital that arises
      during the second transition state of the reaction indicates the addition of the
      hydroxide anion to the carbon atom is forbidden due to orbital symmetry, with a
      similar effect responsible for the failure of a second equivalent of water to add
      to the ccnm anion. Under analogous reaction conditions the addition of 1 equiv of
      methanol to dcnm to form cyano(imino(methoxy)methyl)nitrosomethanide (cmnm,
      [C(CN)(C(OMe)NH)(NO)](-)) failed, although ab initio calculations initially
      indicated the reaction should proceed more readily than the addition of water.
      When the energy required to break the hydrogen-bonded cyclic hexamers in methanol
      is taken into consideration, the energy barrier to the first transition step is
      greatly increased. The addition of a second equivalent of methanol to cmnm is
      unlikely to occur even in the presence of a transition metal as the resultant
      anion would be marginally thermodynamically unstable.

PMID- 21086973
TI  - Influence of structure on the spectroscopic properties of the polymorphs of
      piroxicam.
AB  - The complete (13)C NMR chemical-shift tensors for the carbon sites of the two
      polymorphic forms (P(I) and P(II)) and the monohydrate form (PM) of the analgesic
      drug, piroxicam, are reported. The NMR parameters (isotropic chemical shifts,
      chemical-shielding anisotropies and asymmetries, and dipolar couplings), X-ray
      powder diffraction, and density functional calculations of piroxicam are analyzed
      in terms of hydrogen bonding and structure. The integration of all the data gives
      an improved model of the local solid-state structures of the polymorphs. In
      particular, the solid-state NMR spectra demonstrate that the asymmetric unit of
      the monohydrate, PM, contains two zwitterionic piroxicam molecules.

PMID- 21086974
TI  - Difference in hydration between carboxybetaine and sulfobetaine.
AB  - In this work, we report a study on the differential hydration of carboxybetaine
      and sulfobetaine using molecular simulations. The coordination number, spatial
      distribution, dipole orientation distribution, and residence time of water
      molecules around the positively charged group (N(CH(3))(3)(+)) and negatively
      charged group (COO(-) for carboxybetaine and SO(3)(-) for sulfobetaine) were
      investigated to compare the hydration of these two betaines. The results show
      that the negatively charged group of sulfobetaine has more water molecules around
      it than that of carboxybetaine, while the water molecules around the negatively
      charged group of the carboxybetaine have a sharper spatial distribution, more
      preferential dipole orientation, and longer residence time. The behavior of water
      molecules around the positively charged group of sulfobetaine is similar to those
      around the positively charged group of carboxybetaine. For both sulfobetaine and
      carboxybetaine, the positively charged groups are surrounded by more water
      molecules than the negatively charged groups, whereas the water molecules around
      the negatively charged groups are more ordered than those around the positively
      charged ones. We also investigated the hydration free energy of these two
      molecules with the free energy perturbation method and found that their values
      are all considerably lower than that of oligo(ethylene glycol).

PMID- 21086975
TI  - Rapid, accurate and simple model to predict NMR chemical shifts for biological
      molecules.
AB  - We present a new model to predict chemical shifts for biological molecules. It is
      simple, fast, and involves a limited number of parameters. It is particularly
      adapted to be used in molecular dynamics studies with a molecular mechanic
      potential. We test the model for polyamines, which are rather small molecules, as
      well as for proteins for which a lot of NMR chemical shifts are available. The
      tests show that our simple and fast model is competitive, by its accuracy, with
      sophisticated models specifically developed for proteins. It was also seen to be
      successful for polyamines.

PMID- 21086976
TI  - Molecular dynamics investigation of dipeptide-transition metal salts in aqueous
      solutions.
AB  - Molecular dynamics (MD) simulations of glycylglycine dipeptide with transition
      metal ions (Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+)) in aqueous
      solutions have been carried out to get an insight into the solvation structure,
      intermolecular interactions, and salt effects in these systems. The solvation
      structure and hydrogen bonding were described in terms of radial distribution
      function (RDF) and spatial distribution function (SDF). The dynamical properties
      of the solvation structure were also analyzed in terms of diffusion and residence
      times. The simulation results show the presence of a well-defined first hydration
      shell around the dipeptide, with water molecules forming hydrogen bonds to the
      polar groups of the dipeptide. This shell is, however, affected by the strong
      electric field of divalent metal ions, which at higher ion concentrations lead to
      the shift in the dipeptide-water RDFs. Higher salt concentrations lead also to
      increased residence times and slower diffusion rates. In general, smaller ions
      (Cu(2+), Zn(2+)) demonstrate stronger binding to dipeptide than the larger ones
      (Fe(2+), Mn(2+)). Simulations do not show any stronger association of peptide
      molecules indicating their dissolution in water. The above results may be of
      potential interest to future researchers on these molecular interactions.

PMID- 21086977
TI  - New method based on capillary electrophoresis with laser-induced fluorescence
      detection (CE-LIF) to monitor interaction between nanoparticles and the amyloid
      beta peptide.
AB  - A novel application of capillary electrophoresis with laser-induced fluorescence
      detection (CE-LIF) was proposed to efficiently detect and monitor the interaction
      between polymeric nanoparticles and the beta-Amyloid peptide (Abeta(1-42)), a
      biomarker for Alzheimer's Disease (AD), at concentrations close to physiological
      conditions. The CE-LIF method allowed the interaction between PEGylated
      poly(alkyl cyanoacrylate) nanoparticles (NPs) and the soluble Abeta(1-42) peptide
      monomers to be highlighted. These results were confirmed by surface plasmon
      resonance (SPR) and confocal laser scanning microscopy (CLSM). Whereas SPR showed
      an interaction between the NPs and the Abeta(1-42) peptide, CLSM allowed the
      formation of large aggregates/assemblies at high NP and peptide concentrations to
      be visualized. All these results suggested that these nanoparticles could bind
      the Abeta(1-42) peptide and influence its aggregation kinetics. Interestingly,
      the non-PEGylated poly(alkyl cyanoacrylate) NPs did not alter the aggregation
      kinetics of the Abeta(1-42) peptide, thus emphasizing the high level of
      discrimination of the CE-LIF method with respect to NPs.

PMID- 21086978
TI  - Tamoxifen metabolite isomer separation and quantification by liquid
      chromatography-tandem mass spectrometry.
AB  - Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast
      cancer is a pro-drug that is converted to its major active metabolites, endoxifen
      and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which
      cytochrome P450-2D6 (CYP2D6) is key. The usual Tam dose is 20 mg daily; however,
      the plasma active metabolite concentrations vary due to common genetic variants
      encoding the biotransformation enzymes and environmental factors (e.g.,
      concomitant drugs) that inhibit these enzymes. Effective treatment depends on
      adequate Tam conversion to its active isomers. To monitor metabolite plasma
      levels, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      was developed to separate and quantitate Tam, N-desmethyl-tamoxifen (ND-Tam), and
      tamoxifen-N-oxide (Tam-N-oxide), and the E, Z, and Z' isomers of endoxifen and 4
      OH-Tam. Known standards were used to identify each metabolite/isomer.
      Quantitation of these metabolites in plasma was linear from 0.6 to 2000 nM. Intra
      and inter-assay reproducibilities were 0.2-8.4% and 0.6-6.3%, respectively.
      Accuracy determined by spike experiments with known standards was 86-103%.
      Endoxifen, 4-OH-Tam, and their isomers were stable in fresh frozen plasma for >=6
      months. This method provides the first sensitive, specific, accurate, and
      reproducible quantitation of Tam and its metabolite isomers for monitoring Tam
      treated breast cancer patients.

PMID- 21086979
TI  - NMR study on hydroxy protons of kappa- and kappa/MU-hybrid carrageenan
      oligosaccharides: experimental evidence of hydrogen bonding and chemical exchange
      interactions in kappa/MU oligosaccharides.
AB  - The hydroxy protons of kappa- and kappa/MU-hybrid carrageenan oligosaccharides
      have been studied by NMR spectroscopy in 85% H(2)O/15% acetone-d(6). Hydration
      and hydrogen bonding interactions in di- (kappa), tetra- (kappakappa), hexa
      (kappakappakappa), and octa- (kappakappakappakappa) kappa-oligosaccharides and
      hexa- (kappaMUkappa), octa- (kappaMUMUkappa), and deca- (kappaMUMUMUkappa)
      kappa/MU-oligosaccharides have been investigated by measuring the chemical
      shifts, temperature coefficients, and chemical exchange of the hydroxy protons.
      These NMR parameters indicate that no strong and persistent intramolecular
      hydrogen bonds involving hydroxy protons stabilize the structure of kappa
      carrageenan oligosaccharides in aqueous solution. In the kappa/MU
      oligosaccharides, the presence of chemical exchange between OH3 of alpha-d-Gal-6
      sulfate (D6S) and OH2 of beta-d-Gal-4-sulfate (G4S) across the beta-d-Gal-4-S-(1
      >4)-alpha-d-Gal-6-S linkage reveals the existence of a weak hydrogen bond
      interaction between the two hydroxyl groups. The smaller temperature coefficients
      of OH2_D6S and OH3_D6S indicate reduced hydration, interpreted as spatial
      proximity to the 4-sulfate group and O5 ring oxygen of the neighboring G4S
      residues, respectively. These first experimental results on the conformation of
      kappa/MU-carrageenan oligosaccharides shine light on the potential role of
      "kinks" in the properties of the three-dimensional carrageenan gel network.

PMID- 21086980
TI  - Ligand-mediated highly effective and selective C-N coupling for synthesizing
      bioactive N-aryltriazole acyclonucleosides.
AB  - N-aryltriazole nucleosides are new chemical entities with potential biological
      activity. The two phosphor ligands, Synphos and Xantphos, had a selective and
      effective impact on Pd-catalyzed C-N coupling with the 5- and 3-bromotriazole
      acyclonucleoside isomers, affording the corresponding and otherwise difficult to
      achieve N-aryltriazole nucleosides with good to excellent yields. In addition,
      two of the synthesized nucleosides showed superior anticancer activity against
      drug-resistant pancreatic cancer, compared to the reference drug gemcitabine.

PMID- 21086981
TI  - Shape-controlled synthesis of cobalt-based nanocubes, nanodiscs, and nanoflowers
      and their comparative lithium-storage properties.
AB  - Facile hydrothermal methods have been developed to synthesize large Co3O4
      nanocubes, beta-Co(OH)2 hexagonal nanodiscs and nanoflowers. Samples are
      thoroughly characterized by field-emission scanning electron microscopy,
      transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller
      method, and thermogravimetric analysis. The Co3O4 nanocubes have an average size
      of about 350 nm with a perfect cubic shape, and the beta-Co(OH)2 nanodiscs are
      uniform hexagonal platelets, whereas the beta-Co(OH)2 nanoflowers are assembled
      from large sheetlike subunits. After thermal annealing in air at a moderate
      temperature, the as-prepared beta-Co(OH)2 samples can be converted into spinel
      Co3O4 without significant alterations in morphology. We have also investigated
      the comparative lithium storage properties of these three Co3O4 samples with
      distinct morphologies. The nanoflower sample shows highly reversible lithium
      storage capability after 100 charge-discharge cycles.

PMID- 21086982
TI  - Target-specific cellular uptake of taxol-loaded heparin-PEG-folate nanoparticles.
AB  - To enhance site-specific intracellular delivery against folate receptor, heparin
      PEG-folate (H-PEG-F) containing succinylated-heparin conjugated with folate via
      PEG 1000/3000 spacers has been prepared. Due to covalent strategy, H-PEG-F
      displays amphiphilic property, which is capable of entrapping a hydrophobic
      agent, like taxol, to form heparin-PEG-folate-taxol nanoparticles (H-PEG-F-T NPs)
      in aqueous solution. Hydrophobic agents can be entrapped within the core, while
      the H-PEG-F conjugates can stabilize the nanoparticles with exposing folate
      moieties on the surface. The structure of carrier and naoparticles has been
      characterized by(1)H NMR, and the content of folate and taxol has been
      quantitatively analyzed by UV method. The morphology and size of H-PEG-F-T NPs
      have been measured by field emission scanning electron microscopy (FESEM) and
      dynamic lighting scatter (DLS). All the NPs are in spherical shape and the sizes
      are less than 200 nm. The sizes of the NPs increases with increasing PEG segment
      length. By employing the flow cytomery method, the extent of cellular uptake has
      been comparatively evaluated under various conditions. The results of cellular
      uptake demonstrate that the cellular uptake of the carrier and the NPs is
      exceedingly higher for KB-3-1 cells (folate receptor overexpressing cell line)
      than for A549 cells (folate receptor deficiency cell line); H-PEG-F-T NPs show
      far greater extent of cellular uptake than that of H-PEG-F conjugates against
      A549 cells; when the content of folate is fixed at the same value, the extent of
      cellular uptake for the carrier and NPs ascends with the increase of PEG chain
      length against KB-3-1 cells. It suggests folate-receptor-mediated endocytosis and
      formation of nanoparticle and spacer length are considered to coaffect the
      cellular uptake efficiency of H-PEG-F-T NPs and H-PEG-F conjugates. Flow
      cytometry analysis depicts that KB-3-1 cells treated with H-PEG-F-T are arrested
      in the G(2)/M phase of the cell cycle, which states the similar inhibition
      mechanism as taxol. The strategy based on the formation of H-PEG-F-T NPs could be
      potentially applied for cancer cell targeted delivery of various therapeutic
      agents.

PMID- 21086983
TI  - Natural electroactive hydrogel from soy protein isolation.
AB  - A natural electroactive protein hydrogel was prepared from soy protein isolate
      (SPI) solution by cross-linking with epichlorohydrin. Under electrical stimulus,
      such SPI hydrogel quickly bends toward one electrode, showing a good
      electroactivity. Because of its amphoteric nature, the SPI hydrogel bends either
      toward the anode (pH < 6) or cathode (pH > 6), depending on the pH of the
      electrolyte solution. Other factors, such as electric field strength, ionic
      strength and gel thickness also influence the electromechanical behavior of the
      SPI hydrogels. Moreover, this SPI hydrogel exhibits a good electroactive behavior
      under strong acidic (pH = 2 - 3) or basic (pH = 11 - 12) solutions, which is a
      significant improvement over two other kinds of natural electroactive hydrogels,
      i.e., chitosan/carboxymethylcellulose and chitosan/carboxymethylchitosan
      hydrogel, which we reported previously. The wide pH range and good
      electroactivity of this natural protein hydrogel suggests its great potential for
      microsensor and actuator applications, especially in the biomedical field, and
      also to increase the scope of natural polymer-based electroactive hydrogels.

PMID- 21086984
TI  - Thermodynamic, electrochemical, high-pressure kinetic, and mechanistic studies of
      the formation of oxo Fe(IV)-TAML species in water.
AB  - Stopped-flow kinetic studies of the oxidation of Fe(III)-TAML catalysts, [ F
      e{1,2-X(2)C(6)H(2)-4,5-( NCOCMe(2) NCO)(2)CMe(2)}(OH(2))](-) (1), by t-BuOOH and
      H(2)O(2) in water affording Fe(IV) species has helped to clarify the mechanism of
      the interaction of 1 with primary oxidants. The data collected for substituted
      Fe(III)-TAMLs at pH 6.0-13.8 and 17-45  degrees C has confirmed that the reaction
      is first order both in 1 and in peroxides. Bell-shaped pH profiles of the
      effective second-order rate constants k(I) have maximum values in the pH range of
      10.5-12.5 depending on the nature of 1 and the selected peroxide. The "acidic"
      part is governed by the deprotonation of the diaqua form of 1 and therefore
      electron-withdrawing groups move the lower pH limit of the reactivity toward
      neutral pH, although the rate constants k(I) do not change much. The dissection
      of k(I) into individual intrinsic rate constants k(1) ([FeL(OH(2))(2)](-) +
      ROOH), k(2) ([FeL(OH(2))OH)](2-) + ROOH), k(3) ([FeL(OH(2))(2)](-) + ROO(-)), and
      k(4) ([FeL(OH(2))OH)](2-) + ROO(-)) provides a model for understanding the bell
      shaped pH-profiles. Analysis of the pressure and substituent effects on the
      reaction kinetics suggest that the k(2) pathway is (i) more probable than the
      kinetically indistinguishable k(3) pathway, and (ii) presumably mechanistically
      similar to the induced cleavage of the peroxide O-O bond postulated for
      cytochrome P450 enzymes. The redox titration of 1 by Ir(IV) and electrochemical
      data suggest that under basic conditions the reduction potential for the half
      reaction [Fe(IV)L(=O)(OH(2))](2-) + e(-) + H(2)O -> [Fe(III)L(OH)(OH(2))](2-) +
      OH(-) is close to 0.87 V (vs NHE).

PMID- 21086985
TI  - Ozone impacts of natural gas development in the Haynesville Shale.
AB  - The Haynesville Shale is a subsurface rock formation located beneath the
      Northeast Texas/Northwest Louisiana border near Shreveport. This formation is
      estimated to contain very large recoverable reserves of natural gas, and during
      the two years since the drilling of the first highly productive wells in 2008,
      has been the focus of intensive leasing and exploration activity. The development
      of natural gas resources within the Haynesville Shale is likely to be
      economically important but may also generate significant emissions of ozone
      precursors. Using well production data from state regulatory agencies and a
      review of the available literature, projections of future year Haynesville Shale
      natural gas production were derived for 2009-2020 for three scenarios
      corresponding to limited, moderate, and aggressive development. These production
      estimates were then used to develop an emission inventory for each of the three
      scenarios. Photochemical modeling of the year 2012 showed increases in 2012 8-h
      ozone design values of up to 5 ppb within Northeast Texas and Northwest Louisiana
      resulting from development in the Haynesville Shale. Ozone increases due to
      Haynesville Shale emissions can affect regions outside Northeast Texas and
      Northwest Louisiana due to ozone transport. This study evaluates only near-term
      ozone impacts, but the emission inventory projections indicate that Haynesville
      emissions may be expected to increase through 2020.

PMID- 21086986
TI  - Flexible nets of malleable guardians: intrinsically disordered chaperones in
      neurodegenerative diseases.

PMID- 21086987
TI  - Ordered mesoporous MFe(2)O(4) (M = Co, Cu, Mg, Ni, Zn) thin films with
      nanocrystalline walls, uniform 16 nm diameter pores and high thermal stability:
      template-directed synthesis and characterization of redox active trevorite.
AB  - In this paper, we report on ordered mesoporous NiFe(2)O(4) thin films synthesized
      via co-assembly of hydrated ferric nitrate and nickel chloride with an
      amphiphilic diblock copolymer, referred to as KLE. We establish that the
      NiFe(2)O(4) samples are highly crystalline after calcination at 600  degrees C,
      and that the conversion of the amorphous inorganic framework comes at little cost
      to the ordering of the high quality cubic network of pores averaging 16 nm in
      diameter. We further show that the synthesis method employed in this work can be
      readily extended to other ferrites, such as CoFe(2)O(4), CuFe(2)O(4),
      MgFe(2)O(4), and ZnFe(2)O(4), which could pave the way for innovative device
      design. While this article focuses on the self-assembly and characterization of
      these materials using various state-of-the-art techniques, including electron
      microscopy, grazing incidence small-angle X-ray scattering (GISAXS), time-of
      flight secondary ion mass spectrometry (TOF-SIMS), X-ray photoelectron
      spectroscopy (XPS), as well as UV-vis and Raman spectroscopy, we also examine the
      electrochemical properties and show the benefits of combining a continuous
      mesoporosity with nanocrystalline films. KLE-templated NiFe(2)O(4) electrodes
      exhibit reasonable levels of lithium ion storage at short charging times which
      stem from facile pseudocapacitance.

PMID- 21086988
TI  - Single-source materials for metal-doped titanium oxide: syntheses, structures,
      and properties of a series of heterometallic transition-metal titanium oxo cages.
AB  - Titanium dioxide (TiO(2)) doped with transition-metal ions (M) has potentially
      broad applications in photocatalysis, photovoltaics, and photosensors. One
      approach to these materials is through controlled hydrolysis of well-defined
      transition-metal titanium oxo cage compounds. However, to date very few such
      cages have been unequivocally characterized, a situation which we have sought to
      address here with the development of a simple synthetic approach which allows the
      incorporation of a range of metal ions into titanium oxo cage arrangements. The
      solvothermal reactions of Ti(OEt)(4) with transition-metal dichlorides
      (M(II)Cl(2), M = Co, Zn, Fe, Cu) give the heterometallic transition-metal
      titanium oxo cages [Ti(4)O(OEt)(15)(MCl)] [M = Co (2), Zn (3), Fe (4), Cu (5)],
      having similar MTi(4)(MU(4)-O) structural arrangements involving ion pairing of
      [Ti(4)O(OEt)(15)](-) anion units with MCl(+) fragments. In the case of the
      reaction of MnCl(2), however, two Mn(II) ions are incorporated into this
      framework, giving the hexanuclear Mn(2)Ti(4)(MU(4)-O) cage
      [Ti(4)O(OEt)(15)(Mn(2)Cl(3))] (6) in which the MCl(+) fragments in 2-5 are
      replaced by a [ClMn(MU-Cl)MnCl](+) unit. Emphasizing that the nature of the
      heterometallic cage is dependent on the metal ion (M) present, the reaction of
      Ti(OEt)(4) with NiCl(2) gives [Ti(2)(OEt)(9)(NiCl)](2) (7), which has a dimeric
      Ni(MU-Cl)(2)Ni bridged arrangement arising from the association of
      [Ti(2)(OEt)(9)](-) ions with NiCl(+) units. The syntheses, solid-state
      structures, spectroscopic and magnetic properties of 2-7 are presented, a first
      step toward their applications as precursor materials.

PMID- 21086989
TI  - Synthesis and in vitro cancer cell targeting of folate-functionalized
      biodegradable amphiphilic dendrimer-like star polymers.
AB  - By coupling a well-defined PLLA star polymer with six carboxylic acid-terminated
      polyester dendrons based on 2,2-bis(hydroxymethyl)propionic acid, a biodegradable
      dendrimer-like star polymer (DLSP) with multiple carboxylic acid groups at the
      outer surface was successfully synthesized. Conjugation of amine-functionalized
      folic acids (FA) onto the DLSP yielded a folate-DLSP hybrid as a carrier for
      targeted drug delivery. The chemical structures were proven by proton nuclear
      magnetic resonance and size exclusion chromatography. The DLSPs could form
      unimolecular micelles with a mean particle size of about 18 nm, as determined by
      dynamic light scattering. Flow cytometry and confocal microscope studies revealed
      that the cellular uptake of the folate-DLSP hybrid against KB cells
      (overexpressed folate-receptor) was much higher than that of the neat DLSP
      (without FA) due to the folate receptor-mediated binding.

PMID- 21086990
TI  - Molecule-electrode bonding design for high single-molecule conductance.
AB  - We report the application of an intermolecular interaction design for organic
      conductor crystals with a high conductance to a molecule-electrode design for a
      high single-molecule conductance by using dithiol and diselenol terthiophenes. We
      found that dithiol and diselenol single-molecule junctions show the highest
      single-molecule conductance among single-molecule junctions with Au-S and Au-Se
      bonds, and that diselenol single-molecule junctions have a higher single-molecule
      conductance than dithiol ones. We demonstrate that replacing S atoms with Se
      atoms is a promising molecule-electrode bonding design for a high single-molecule
      conductance.

PMID- 21086991
TI  - Electrostatic chameleons in biological systems.
AB  - Due to large equilibrium fluctuations of protons at physiological pH, the
      orthophosphate ion as well as the imidazole group on histidine substantially
      regulate their charge upon approaching charged interfaces. This implies that
      these-and comparable-ions function as electostatic "proximity switches" when
      interacting with lipid membranes, DNA, proteins, etc. Using straightforward
      statistical thermodynamics as well as mesoscopic computer simulations we quantify
      the charge regulation mechanism and argue that it is important in a range of
      biological as well as technical processes.

PMID- 21086993
TI  - Reorganization and caging of DPPC, DPPE, DPPG, and DPPS monolayers caused by
      dimethylsulfoxide observed using Brewster angle microscopy.
AB  - The interaction between dimethylsulfoxide (DMSO) and phospholipid monolayers with
      different polar headgroups was studied using "in situ" Brewster angle microscopy
      (BAM) coupled to a Langmuir trough. For a 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) monolayer, DMSO was shown to significantly impact the
      structure of the liquid expanded (LE) and gaseous phases. The domains reorganized
      to much larger domain structures. Domains in the liquid condensed (LC) phase were
      formed on the DMSO-containing subphase at the mean molecular area where only
      gaseous and LE phases were previously observed on the pure water subphase. These
      results clearly demonstrate the condensing and caging effect of DMSO molecules on
      the DPPC monolayer. Similar effects were found on dipalmitoyl phosphatidyl
      ethanolamine, glycerol, and serine phospholipids, indicating that the condensing
      and caging effect is not dependent upon the phospholipid headgroup structure. The
      DMSO-induced condensing and caging effect is the molecular mechanism that may
      account for the enhanced permeability of membranes upon exposure to DMSO.

PMID- 21086994
TI  - Synthesis of well-defined graft copolymers by combination of enzymatic
      polycondensation and "click" chemistry.
AB  - Aliphatic polyesters having pendant azide groups were prepared by enzymatic
      polycondensation in the presence of lipase from Candida antarctica type B (CAL
      B). The grafting reaction to the N(3)-functional polyester was carried out
      quantitatively at room temperature using copper-catalyzed azide-alkyne
      cycloaddition (CuAAC, "click" reaction) with monoalkyne-functional poly(ethylene
      oxide) (alkyne-PEO, M(n) = 750 g/mol). Furthermore, both enzymatic
      polycondensation and "click" reaction were carried out successfully in sequential
      one-pot reaction. The graft copolymer was surface-active and self-assembled in
      water. The graft copolymer had a critical aggregation concentration (cac) of 3 *
      10(-2) MUM in water determined by surface tension measurements. Above cac, the
      graft copolymer formed single chains and aggregates having a hydrodynamic radius
      of ~75 nm. Furthermore, the surface activity of the polymers at the air-water
      interface was studied by Langmuir trough measurements. The Langmuir isotherm of
      the graft polymer showed a pseudoplateau resulting from desorption of PEO chains
      into the subphase upon compression.

PMID- 21086995
TI  - Controlled buckling and crumpling of nanoparticle-coated droplets.
AB  - We introduce a new experimental approach to study the structural transitions of
      large numbers of nanoparticle-coated droplets as their volume is reduced. We use
      an emulsion system where the dispersed phase is slightly soluble in the
      continuous phase. By adding a fixed amount of unsaturated continuous phase, the
      volume of the droplets can be controllably reduced, causing them to buckle or
      crumple, thereby becoming nonspherical. The resultant morphologies depend both on
      the extent of volume reduction and the average droplet size. The buckling and
      crumpling behavior implies that the droplet surfaces are solid.

PMID- 21086996
TI  - A novel method of fabrication of latex-stabilized water-core colloidosomes at
      room temperature.
AB  - Colloidosomes have attracted great interest in recent years because of the
      capability of storage and delivery of useful materials in various fields. In this
      article, a novel technique for formation of colloidosomes at room temperature
      suitable for encapsulation of biomaterials was examined. We demonstrate the
      formation of colloidosomes of 18.0 MUm in size at room temperature by adding a
      small amount of ethanol into the continuous phase of sunflower oil. Poly(methyl
      methacrylate-co-butyl acrylate) latex particles of 185 nm in size, used in this
      study, were found to aggregate when ethanol was added to their suspension. We
      suggest that the shell of the water-core emulsions was locked by the aggregation
      of latex particles due to the diffusion of ethanol into the aqueous latex
      suspension.

PMID- 21086997
TI  - Nature's design of hierarchical superhydrophobic surfaces of a water strider for
      low adhesion and low-energy dissipation.
AB  - The mechanics of wet adhesion between a water strider's legs and a water surface
      was studied. First, we showed that the nanoscale to microscale hierarchical
      surface structure on striders' legs is crucial to the stable water-repellent
      properties of the legs. The smallest structure is made for the sake of a stable
      Cassie state even under harsh environment conditions, which sets an upper limit
      for the dimension of the smallest structure. The maximum stress and the maximum
      deformation of the surface structures at the contact line are size-dependent
      because of the asymmetric surface tension, which sets a lower limit for the
      dimension of the smallest structure. The surface hierarchy can largely reduce the
      adhesion between the water and the legs by stabilizing the Cassie state,
      increasing the apparent contact angle, and reducing the contact area and the
      length of the contact line. Second, the processes of the legs pressing on and
      detaching from the water surface were analyzed with a 2D model. We found that the
      superhydrophobicity of the legs' surface is critically important to reducing the
      detaching force and detaching energy. Finally, the dynamic process of the legs
      striking the water surface, mimicking the maneuvering of water striders, was
      analyzed. We found that the large length of the legs not only reduces the energy
      dissipation in the quasi-static pressing and pulling processes but also enhances
      the efficiency of energy transfer from bioenergy to kinetic energy in the dynamic
      process during the maneuvering of the water striders. The mechanical principles
      found in this study may provide useful guidelines for the design of superior
      water-repellent surfaces and novel aquatic robots.

PMID- 21086998
TI  - Solar UVB response of bioactives in strawberry (Fragaria * ananassa Duch. L.): a
      comparison of protected and open-field cultivation.
AB  - Strawberries (Fragaria * ananassa Duch. cvs. Everest, Elsanta) were grown in a
      tunnel covered with two films, which were distinguished in their ultraviolet
      transparency, as well as under open-field conditions. One applied film was not
      transparent for UVB radiation, and the second film transmitted 70% of UVB
      radiation. During the present study, the nutritional value and quality parameters
      of the fruits were evaluated. Strawberries were UV-unresponsive in view of the
      content of ascorbic acid and sum parameters like total anthocyanins and
      antioxidant capacity measured with TEAC (trolox equivalent antioxidant capacity),
      ORAC (oxygen radical absorbance capacity) and total phenols. These parameters
      were mainly affected by sampling date and cultivar. However, HPLC analysis showed
      that individual phenolics were affected in the absence of UV radiation. The
      content of the anthocyanin cyanidin 3-glucoside and the flavonols quercetin 3
      glucuronide and kaempferol 3-glucoside was decreased in the fruits grown under UV
      blocking film compared to open-field grown strawberries. By means of the UV
      transparent film the content of the mentioned flavonoids could be enhanced up to
      similar amounts like in open-field grown strawberries. All other phenolics were
      not consistently affected by UV radiation. This result was independent of
      cultivar.

PMID- 21086999
TI  - Concentrated diffusing colloidal probes of Ca2+-dependent cadherin interactions.
AB  - We report video microscopy measurements and inverse simulation analyses of
      specific Ca(2+)-dependent interactions between N-cadherin fragments attached to
      supported lipid bilayer-coated silica colloids in quasi-2D concentrated
      configurations. Our results include characterization of the bilayer formation and
      fluidity and the attachment of active extracellular cadherin fragments on
      bilayers. Direct measurements of interaction potentials show nonspecific
      macromolecular repulsion between cadherin fragments in the absence of Ca(2+) and
      irreversible bilayer fusion via cadherin-mediated attraction at >100 MUM Ca(2+).
      Analysis of Ca(2+)-dependent N-cadherin bond formation in quasi-2D concentrated
      configurations using inverse Monte Carlo and Brownian Dynamics simulations show
      measurable attraction starting at 0.1 MUM Ca(2+), a concentration significantly
      below previously reported values.

PMID- 21087000
TI  - Reactivity of functionalized N,S-ketene acetal: regioselective construction of
      tetrahydrobenzo[b]pyran and chromeno[2,3-b]quinoline derivatives.
AB  - Regioselective synthesis of functionalized tetrahydrobenzo[b]pyrans has been
      developed by multicomponent reactions (MCRs) and tandem [3 + 3] annulations of
      beta-benzoylthioacetanilides or beta-(2-haloaroyl)thioacetanilides as valuable
      sources with aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione catalyzed
      by triethylamine. This MCR followed by a postcondensation cyclization via an
      intramolecular S(N)Ar in the presence of K(2)CO(3) led to an unprecedented novel
      chromeno[2,3-b]quinoline framework containing an important chromene moiety in
      good yields. The reactions were very mild, convenient, and o-selective to form
      new fused tetracyclic target molecules.

PMID- 21087001
TI  - Exciton formation, relaxation, and decay in PCDTBT.
AB  - The nature and time evolution of the primary excitations in the pristine
      conjugated polymer, PCDTBT, are investigated by femtosecond-resolved fluorescence
      up-conversion spectroscopy. The extensive study includes data from PCDTBT thin
      film and from PCDTBT in chlorobenzene solution, compares the fluorescence
      dynamics for several excitation and emission wavelengths, and is complemented by
      polarization-sensitive measurements. The results are consistent with the
      photogeneration of mobile electrons and holes by interband pi-pi* transitions,
      which then self-localize within about 100 fs and evolve to a bound singlet
      exciton state in less than 1 ps. The excitons subsequently undergo successive
      migrations to lower energy localized states, which exist as a result of disorder.
      In parallel, there is also slow conformational relaxation of the polymer
      backbone. While the initial self-localization occurs faster than the time
      resolution of our experiment, the exciton formation, exciton migration, and
      conformational changes lead to a progressive relaxation of the inhomogeneously
      broadened emission spectrum with time constants ranging from about 500 fs to tens
      of picoseconds. The time scales found here for the relaxation processes in
      pristine PCDTBT are compared to the time scale (<0.2 ps) previously reported for
      photoinduced charge transfer in phase-separated PCDTBT:fullerene blends (Phys.
      Rev. B 2010, 81, 125210). We point out that exciton formation and migration in
      PCDTBT occur at times much longer than the ultrafast photoinduced electron
      transfer time in PCDTBT:fullerene blends. This disparity in time scales is not
      consistent with the commonly proposed idea that photoinduced charge separation
      occurs after diffusion of the polymer exciton to a fullerene interface. We
      therefore discuss alternative mechanisms that are consistent with ultrafast
      charge separation before localization of the primary excitation to form a bound
      exciton.

PMID- 21087002
TI  - Functional hollow carbon nanospheres by latex templating.
AB  - A facile and sustainable synthesis of hollow carbonaceous nanospheres is
      presented, offering a scalable and multifunctional route to the generation of
      useful nanocontainers, which critically possess the stability not offered by
      polymeric equivalents and functionality not afforded by other nanocarbons.
      Carbonization temperature provides a subtle but elegant mechanism to control
      structure and thereby hydrophobicity, nanopartitioning, and permeation between
      the inner and outer space.

PMID- 21087003
TI  - Palladium-catalyzed asymmetric synthesis of allylic fluorides.
AB  - The enantioselective fluorination of readily available cyclic allylic chlorides
      with AgF has been accomplished using a Pd(0) catalyst and Trost bisphosphine
      ligand. The reactions proceed with unprecedented ease of operation for Pd
      mediated nucleophilic fluorination, allowing access to highly enantioenriched
      cyclic allylic fluorides that bear diverse functional groups. Evidence that
      supports a mechanism in which C-F bond formation occurs by an S(N)2-type attack
      of fluoride on a Pd(II)-allyl intermediate is presented.

PMID- 21087004
TI  - Electromagnetic micropores: fabrication and operation.
AB  - We describe the fabrication and characterization of electromagnetic micropores.
      These devices consist of a micropore encompassed by a microelectromagnetic trap.
      Fabrication of the device involves multiple photolithographic steps, combined
      with deep reactive ion etching and subsequent insulation steps. When immersed in
      an electrolyte solution, application of a constant potential across the micropore
      results in an ionic current. Energizing the electromagnetic trap surrounding the
      micropore produces regions of high magnetic field gradients in the vicinity of
      the micropore that can direct motion of a ferrofluid onto or off of the
      micropore. This results in dynamic gating of the ion current through the
      micropore structure. In this report, we detail fabrication and characterize the
      electrical and ionic properties of the prepared electromagnetic micropores.

PMID- 21087005
TI  - Adsorption, desorption, and surface-promoted hydrolysis of glucose-1-phosphate in
      aqueous goethite (alpha-FeOOH) suspensions.
AB  - Adsorption, desorption, and precipitation reactions at environmental interfaces
      govern the fate of phosphorus in terrestrial and aquatic environments. Typically,
      a substantial part of the total pool of phosphorus consists of organophosphate,
      and in this study we have focused on the interactions between glucose-1-phosphate
      (G1P) and goethite (alpha-FeOOH) particles. The adsorption and surface-promoted
      hydrolysis reactions have been studied at room temperature as a function of pH,
      time, and total concentration of G1P by means of quantitative batch experiments
      in combination with infrared spectroscopy. A novel simultaneous infrared and
      potentiometric titration (SIPT) technique has also been used to study the rates
      and mechanisms of desorption of the surface complexes. The results have shown
      that G1P adsorption occurs over a wide pH interval and at pH values above the
      isoelectric point of goethite (IEP(goethite) = 9.4), indicating a comparatively
      strong interaction with the particle surfaces. As evidenced by IR spectroscopy,
      G1P formed pH-dependent surface complexes on goethite, and investigations of both
      adsorption and desorption processes were consistent with a model including three
      types of surface complexes. These complexes interact monodentately with surface
      Fe but differ in hydrogen bonding interactions via the auxiliary oxygens of the
      phosphate group. The apparent desorption rates were shown to be influenced by
      reaction pathways that include interconversion of surface species, which
      highlights the difficulty in determining the intrinsic desorption rates of
      individual surface complexes. Desorption results have also indicated that the
      molecular structures of surface complexes and the surface charge are two
      important determinants of G1P desorption rates. Finally, this study has shown
      that surface-promoted hydrolysis of G1P by goethite is base-catalyzed but that
      the extent of hydrolysis was small.

PMID- 21087006
TI  - Tethering hydrophobic peptides to functionalized self-assembled monolayers on
      gold through two chemical linkers using the Huisgen cycloaddition.
AB  - Gold surfaces functionalized with an alpha-helical peptide have been generated by
      reacting an azide-terminated self-assembled monolayer with structured peptides
      containing two cyanophenylalanines through a Huisgen cycloaddition. Mixed
      monolayers of a reactive bromine-terminated thiol and inert alkane thiol were
      prepared at various concentrations of the Br-terminated moiety. These were
      reacted with sodium azide to form azide-terminated monolayers with controlled
      concentration of the reactive azide. These surfaces were studied through
      ellipsometry and X-ray photoelectron spectroscopy, which demonstrated that the
      concentration of the reactive azide group on the surface is controlled by the
      chemical conditions under which the monolayer is prepared. Grazing incident angle
      surface infrared spectroscopy (GRAS-IR) of the azide-terminated surface
      demonstrated that the azide is approximately perpendicular to the plane of the
      surface, as expected. These surfaces were then exposed to an alpha-helical
      peptide composed of alternating leucine and lysine residues, with two residues
      replaced with cyanophenylalanine to react with two neighboring surface-bound
      azide groups to bind the peptide to the surface through two covalent bonds. The
      yield of this reaction was quantified through monitoring the absorption of the
      azide group by GRAS-IR. Despite damage to the monolayer during the reaction,
      reaction yields of 80-98% were determined for optimized reaction conditions.
      Although the peptide retains its alpha-helical configuration under the reaction
      conditions, GRAS-IR analysis of the amide I and II modes of the surface-bound
      peptide showed that it is probably randomly oriented on the surface.

PMID- 21087007
TI  - Effect of hydrophilic groups of Ca surfactants and hydrophobic chains of C(n)DMAO
      on coordinated vesicle formation.
AB  - The effects of hydrophilic headgroups of Ca surfactants, calcium dodecylsulfate
      (Ca(DS)(2)), calcium dodecylsulfonate (Ca(DSA)(2)), and calcium laurate (CaL(2))
      and hydrophobic chains of alkyldimethylamine oxide (C(n)DMAO, n = 12, 14, 16) on
      the formation of Ca(2+)-ligand coordinated vesicles was investigated in detail.
      On the basis of phase behavior studies, rheological properties and freeze
      fracture transmission electron microscope (FF-TEM) images were measured. Quite
      different phase behaviors were observed in different surfactant systems. For a Ca
      surfactant with a highly polar group, Ca(DS)(2), vesicles were observed in all
      Ca(DS)(2)/C(n)DMAO (n = 12, 14, and 16) systems, whereas for Ca surfactant with
      lower polar group, Ca(DSA)(2), vesicles can form in Ca(DSA)(2)/C(n)DMAO systems
      of n = 14 and 16 but not for n = 12. For CaL(2), the surfactant with the least
      polar group, vesicles form only in the CaL(2)/C(16)DMAO system. The results
      demonstrate that in the systems formed by Ca surfactants and C(n)DMAO, the
      formation of vesicles is driven not only by interaction between Ca(2+) and the N 
      > O groups of C(n)DMAO but also by electrostatic and hydrophobic interactions.
      Vesicles prefer to form in Ca surfactants with highly polar headgroups and
      C(n)DMAO with long chain length.

PMID- 21087008
TI  - Toward the total synthesis of maoecrystal V: establishment of contiguous
      quaternary stereocenters.
AB  - A synthetic strategy toward maoecrystal V has been identified. It has been shaped
      by the necessity to maneuver in sterically hindered molecular environments.

PMID- 21087009
TI  - Serendipitous discovery of alpha-hydroxyalkyl esters as beta-lactamase
      substrates.
AB  - O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously
      decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl)
      hydroxamates. While the former molecules do not react rapidly with serine beta
      lactamases, the latter are quite good substrates of representative class A and C,
      but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze
      hydrolysis of these compounds to a mixture of the alpha-hydroxy acid and
      hydroxamate. Analogous compounds containing aryloxy leaving groups rather that
      hydroxamates are also substrates. Structure-activity experiments showed that the
      alpha-hydroxyl group was required for any substantial substrate activity.
      Although both d- and l-alpha-hydroxy acid derivatives were substrates, the former
      were preferred. The response of the class C activity to pH and to alternative
      nucleophiles (methanol and d-phenylalanine) suggested that the same active site
      functional groups participated in catalysis as for classical substrates.
      Molecular modeling was employed to explore how the alpha-hydroxy group might
      interact with the class C beta-lactamase active site. Incorporation of the alpha
      hydroxyalkyl moiety into novel inhibitors will be of considerable interest.

PMID- 21087010
TI  - Hierarchical self-assembly of bolaamphiphiles with a hybrid spacer and L-glutamic
      acid headgroup: pH- and surface-triggered hydrogels, vesicles, nanofibers, and
      nanotubes.
AB  - Bolaamphiphiles with L-glutamic acid headgroups and hybrid linkers, each composed
      of two rigid benzene rings and different polymethylene units, were designed, and
      morphological controls of the hierarchical self-assemblies were realized via
      changing solution pH and application to solid surfaces. At a low pH of 3,
      bolaamphiphiles formed hydrogels with water and molecules with short and long
      spacers formed nanofibers and helical nanoribbon-nanotubes, respectively. In a pH
      12 aqueous solution, vesicles were observed from cryo-TEM measurements for
      amphiphiles with short spacers that could transfer to huge vesicles when cast
      onto a mica surface. Amphiphiles with longer spacers self-assembled into
      nanoparticles in a pH 12 aqueous solution while micellar fibers were formed on a
      mica surface. Those assemblies were characterized with UV-vis, CD, and FT-IR
      spectroscopy and AFM and TEM observations. With molecular structure modification
      and the fine tuning of conditions, morphology transitions between various
      nanostructures were obtained from the self-assembled bolaamphiphiles. The
      environmental pH can induce different interaction modes between the headgroups,
      and at high pH, there are strong interactions between molecular assemblies and
      the mica surface. It is suggested that the active headgroups, rigid necks, and
      flexible linkers with different lengths render molecules with diverse aggregation
      morphologies.

PMID- 21087011
TI  - Phosphite-containing ligands for asymmetric catalysis.

PMID- 21087012
TI  - Catalysis by palladium pincer complexes.

PMID- 21087013
TI  - Elucidating the ionomer-electrified metal interface.
AB  - The competitive adsorption of Nafion functional groups induce complex potential
      dependencies (Stark tuning) of vibrational modes of CO adsorbed (CO(ads)) on the
      Pt of operating fuel cell electrodes. Operando infrared (IR) spectroscopy,
      polarization modulated IR spectroscopy (PM-IRRAS) of Pt-Nafion interfaces, and
      attenuated total reflectance IR spectroscopy of bulk Nafion were correlated by
      density functional theory (DFT) calculated spectra to elucidate Nafion functional
      group coadsorption responsible for the Stark tuning of CO(ads) on high surface
      area fuel cell electrodes. The DFT calculations and observed spectra suggest that
      the side-chain CF3, CF2 groups (i.e., of the backbone and side chain) and the
      SO3(-) are ordered by the platinum surface. A model of the Nafion-Pt interface
      with appropriate dihedral and native bond angles, consistent with experimental
      and calculated spectra, suggest direct adsorption of the CF3 and SO3(-)
      functional groups on Pt. Such adsorption partially orders the Nafion backbone
      and/or side-chain CF2 groups relative to the Pt surface. The coadsorption of CF3
      is further supported by Mulliken partial charge calculations: The CF3 fluorine
      atoms have the highest average charge among all types of Nafion fluorine atoms
      and are second only to the sulfonate oxygen atoms.

PMID- 21087015
TI  - Structure-induced ferromagnetic stabilization in free-standing hexagonal
      Fe(1.3)Ge nanowires.
AB  - Single-crystalline free-standing hexagonal Fe(1.3)Ge nanowires (NWs) are
      synthesized for the first time using a chemical vapor transport process without
      using any catalyst. Interestingly, Fe(1.3)Ge NWs are found to be ferromagnetic at
      room temperature, while bulk Fe(1.3)Ge has the lower critical temperature of 200
      K. We perform first-principles density functional calculations and suggest that
      the observed strong ferromagnetism is attributed to the reduced distances between
      Fe atoms, increased number of Fe-Fe bonds, and the enhanced Fe magnetic moments.
      Both experimental and theoretical studies show that the magnetic moments are
      enhanced in the NWs, as compared to bulk Fe(1.3)Ge. We also modulate the
      composition ratio of as-grown iron germanide NWs by adjusting experimental
      conditions. It is shown that uniaxial strain on the hexagonal plane also enhances
      the ferromagnetic stability.

PMID- 21087014
TI  - Carborane-conjugated 2-quinolinecarboxamide ligands of the translocator protein
      for boron neutron capture therapy.
AB  - Potential boron neutron capture therapy (BNCT) agents have been designed on the
      basis of the evidence about translocator protein (TSPO) overexpression on the
      outer mitochondrial membrane of tumor cells. The structure of the first TSPO
      ligand bearing a carborane cage (compound 2d) has been modified in order to find
      a suitable candidate for in vivo studies. The designed compounds were synthesized
      and evaluated for their potential interaction with TSPO and tumor cells. In vitro
      biological evaluation showed in the case of fluoromethyl derivative 4b a
      nanomolar TSPO affinity very similar to that of 2d, a significantly lower
      cytotoxicity, and a slightly superior performance as boron carrier toward breast
      cancer cells. Moreover, compound 4b could be used as a 19F magnetic resonance
      imaging (MRI) agent as well as labeled with 11C or 18F to obtain positron
      emission tomography (PET) radiotracers in order to apply the "see and treat"
      strategy in BNCT.

PMID- 21087016
TI  - Hydration is a major determinant of the G-quadruplex stability and conformation
      of the human telomere 3' sequence of d(AG3(TTAG3)3).
AB  - The factors that determine the conformation and stability of G-quadruplex forming
      sequences remain poorly understood. Here we demonstrate the influence of
      cosolvents on the conformation and stability of the human telomeric sequence
      d(A(GGGTTA)3GGG)) in both K(+) and Na(+) containing solutions using a combination
      of circular dichroism, NMR, and thermodynamics. Molecular crowding arguments have
      previously been used to suggest that the parallel quadruplex form may be
      biologically relevant. However, the small cosolvents previously used, PEG 200 and
      400, are actually dehydrating agents. We have used acetonitrile as a non-hydrogen
      bonding dehydrating agent; similar conformational transitions were observed in
      K(+) solution. Moreover, NMR analysis shows that the resulting structure contains
      non-anti guanine glycosyl torsion angles suggesting that the conformation present
      in acetonitrile is not identical to the all-parallel crystal structure, despite
      the supposed parallel type CD spectrum.

PMID- 21087017
TI  - Triterpenoids from Aglaia abbreviata and their cytotoxic activities.
AB  - Six new triterpenoids (1-6), along with 10 known compounds, were isolated from
      the stems of Aglaia abbreviata. The structures of 1-6 were elucidated on the
      basis of their spectroscopic data. Compounds 1-6 were evaluated for their
      cytotoxic activities against a small panel of human tumor cell lines.

PMID- 21087018
TI  - The agminosides: naturally acetylated glycolipids from the New Zealand marine
      sponge Raspailia agminata.
AB  - Examination of the New Zealand sponge Raspailia agminata resulted in the
      isolation of five members of a novel family of glycolipids, agminosides A-E (1
      5). These large and complex molecules contain up to six partially acetylated
      glucose residues. The chromatographic separation of these compounds was a
      challenge due to the similarity of the congeners and their lack of a chromophore.
      MS-guided isolation followed by extensive NMR analysis and chemical
      derivatization eventually led to the purification and identification of 1-5.

PMID- 21087020
TI  - Mixed valency across hydrogen bonds.
AB  - An oxo-centered triruthenium cluster with one pyridine-4-carboxylic acid ligand
      forms a mixed valence monoanionic dicarboxylic acid dimer upon partial reduction.
      Dimerization is not observed in DMSO or in the deprotonated carboxylate complex.
      Infrared spectroscopy reveals the mixed valence dimer as a charge localized
      species, and UV/vis/NIR spectroscopy suggests a large stabilization of the ground
      state by mixed valency across hydrogen bonds, on the order of 2500 cm(-1), or 7
      kcal/mol, relative to the hydrogen bonded but isovalent fully reduced dimer. The
      stabilization is a combination of hydrogen bonding and electronic coupling.

PMID- 21087019
TI  - Protective effects of baicalin against ischemia/reperfusion injury in rat liver.
AB  - The cytoprotective properties of baicalin (1), a flavonoid glycoside isolated
      from Scutellaria baicalensis, have been investigated against injury to the liver
      caused by ischemia/reperfusion (I/R). Rats were subjected to 60 min of ischemia
      followed by 5 h of reperfusion, and 1 was administered intraperitoneally 24 and 1
      h before ischemia. Following I/R, the levels of serum alanine aminotransferase
      and hepatic lipid peroxidation were elevated, whereas the hepatic glutathione
      content was decreased, with these changes attenuated by 1. Serum levels of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 were markedly increased
      by I/R, but suppressed by 1. Baicalin attenuated increases in inducible nitric
      oxide synthase, cyclooxygenase (COX)-2, and TNF receptor 1-associated protein
      expression and augmented an increase in heme oxygenase-1 (HO-1). The increase in
      TNF-alpha, IL-6, and, COX-2 mRNA expression was attenuated by 1, while the
      increase in HO-1 mRNA expression was augmented. Nuclear factor-kappaB nuclear
      localization was inhibited by 1, and this compound limited the rate of
      mitochondrial swelling and the activation of caspases-3 and -8 observed in I/R
      rats. Rats treated with 1 had markedly fewer apoptotic cells than I/R rats. It
      was concluded that baicalin (1) exhibits antioxidant, anti-inflammatory, and
      antiapoptotic effects, which protect against hepatocellular I/R-induced damage.

PMID- 21087021
TI  - Kinetic resolution of homoaldols via catalytic asymmetric transacetalization.
AB  - The highly enantioselective kinetic resolution of homoaldols via a
      transacetalization reaction has been achieved. A novel phosphoric acid, STRIP,
      based on a spirocyclic 1,1'-spirobiindane backbone was designed and identified as
      a superior catalyst for this transformation. Remarkably, both secondary and
      tertiary homoaldols gave equally excellent results.

PMID- 21087022
TI  - Hypersonic vibrations of Ag@SiO2 (cubic core)-shell nanospheres.
AB  - The intriguing optical and catalytic properties of metal-silica core-shell
      nanoparticles, inherited from their plasmonic metallic cores together with the
      rich surface chemistry and increased stability offered by their silica shells,
      have enabled a wide variety of applications. In this work, we investigate the
      confined vibrational modes of a series of monodisperse Ag@SiO(2) (cubic core)
      shell nanospheres synthesized using a modified Stober sol-gel method. The
      particle-size dependence of their mode frequencies has been mapped by Brillouin
      light scattering, a powerful tool for probing hypersonic vibrations. Unlike the
      larger particles, the observed spheroidal-like mode frequencies of the smaller
      ones do not scale with inverse diameter. Interestingly, the onset of the
      deviation from this linearity occurs at a smaller particle size for higher-energy
      modes than for lower-energy ones. Finite element simulations show that the mode
      displacement profiles of the Ag@SiO(2) core-shells closely resemble those of a
      homogeneous SiO(2) sphere. Simulations have also been performed to ascertain the
      effects that the core shape and the relative hardness of the core and shell
      materials have on the vibrations of the core-shell as a whole. As the vibrational
      modes of a particle have a bearing on its thermal and mechanical properties, the
      findings would be of value in designing core-shell nanostructures with customized
      thermal and mechanical characteristics.

PMID- 21087023
TI  - Heat of freezing for supercooled water: measurements at atmospheric pressure.
AB  - Unlike reversible phase transitions, the amount of heat released upon freezing of
      a metastable supercooled liquid depends on the degree of supercooling. Although
      terrestrial supercooled water is ubiquitous and has implications for cloud
      dynamics and nucleation, measurements of its heat of freezing are scarce. We have
      performed calorimetric measurements of the heat released by freezing water at
      atmospheric pressure as a function of supercooling. Our measurements show that
      the heat of freezing can be considerably below one predicted from a reversible
      hydrostatic process. Our measurements also indicate that the state of the
      resulting ice is not fully specified by the final pressure and temperature; the
      ice is likely to be strained on a variety of scales, implying a higher vapor
      pressure. This would reduce the vapor gradient between supercooled water and ice
      in mixed phase atmospheric clouds.

PMID- 21087024
TI  - Studies on the structure and stability of cyclic peptide based nanotubes using
      oligomeric approach: a computational chemistry investigation.
AB  - In this study, an attempt has been made to investigate the structure, dynamics,
      and stability of cyclic peptide nanotubes (CPNTs) formed by the self-assembly of
      cyclic peptides (CPs) using classical molecular dynamics (MD) simulation and
      semiempirical quantum chemistry calculation employing PM6 Hamiltonian with the
      dispersion correction and hydrogen-bonding interaction (DH2). The structure and
      energetics of monomer and various oligomeric CPNTs have been investigated by
      considering the (cyclo-[(D-Ala-L-Ala)(4)]) peptide as the model for CP. Although
      the formation of CPNTs has been intensively studied, the present study adds
      valuable information to the de novo design of CPNTs. Various geometrical
      parameters extracted from the MD simulation reveal that the terminal residues are
      loosely hydrogen bonded to the inner subunits regardless of degree of
      oligomerization. The hydrogen bonds present in the inner core regions are
      stronger than the terminal residues. As the degree of oligomerization increases,
      the stability of the tube increases due to the hydrogen-bonding and stacking
      interactions between the subunits. The results show that the binding free energy
      increases with the extent of oligomerization and reaches saturation beyond
      pentamer CPNT. In addition, hydrophobic and electrostatic interactions play
      crucial roles in the formation of CPNTs. Analysis of both structure and
      energetics of the formation of CPNTs unveils that the self-assembly of dimer,
      trimer, and tetramer CPNTs are the essential steps in the growth of CPNTs.

PMID- 21087025
TI  - Examining India's groundwater quality management.

PMID- 21087026
TI  - Immobilization of acetylcholinesterase in lipid membranes deposited on self
      assembled monolayers.
AB  - Human red blood cell acetylcholinesterase was incorporated into planar lipid
      membranes deposited on alkanethiol self-assembled monolayers (SAMs) on gold
      substrates. Activity of the protein in the membrane was detected with a standard
      photometric assay and was determined to be similar to the protein in detergent
      solution or incorporated in lipid vesicles. Monolayer and bilayer lipid membranes
      were generated by fusing liposomes to hydrophobic and hydrophilic SAMs,
      respectively. Liposomes were formed by the injection method using the lipid
      dimyristoylphosphatidylcholine (DMPC). The formation of alkanethiol SAMs and
      lipid monolayers on SAMs was confirmed by sessile drop goniometry, ellipsometry,
      and electrochemical impedance spectroscopy. In this work, we report
      acetylcholinesterase immobilization in lipid membranes deposited on SAMs formed
      on the gold surface and compare its activity to enzyme in solution.

PMID- 21087027
TI  - Proton transport properties in zwitterion blends with Bronsted acids.
AB  - We describe zwitterion, 3-(1-butyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate
      (Bimps), mixtures with 1,1,1-trifluoro-N
      (trifluoromethylsulfonyl)methanesulfoneamide (HN(Tf)(2)) as new proton transport
      electrolytes. We report proton transport mechanisms in the mixtures based on
      results from several methods including thermal analyses, the complex-impedance
      method, and the pulsed field gradient spin echo NMR (pfg-NMR) method. The glass
      transition temperature (Tg) of the mixtures decreased with increasing HN(Tf)(2)
      concentration up to 50 mol %. The Tg remained constant at -55  degrees C with
      further acid doping. The ionic conductivity of HN(Tf)(2) mixtures increased with
      the HN(Tf)(2) content up to 50 mol %. Beyond that ratio, the mixtures showed no
      increase in ionic conductivity (10(-4) S cm(-1) at room temperature). This
      tendency agrees well with that of Tg. However, the self-diffusion coefficients
      obtained from the pfg-NMR method increased with HN(Tf)(2) content even above 50
      mol % for all component ions. At HN(Tf)(2) 50 mol %, the proton diffusion of
      HN(Tf)(2) was the fastest in the mixture. These results suggest that Bimps cannot
      dissociate excess HN(Tf)(2), that is, the excess HN(Tf)(2) exists as molecular
      HN(Tf)(2) in the mixtures. The zwitterion, Bimps, forms a 1:1 complex with
      HN(Tf)(2) and the proton transport property in this mixture is superior to those
      of other mixing ratios. Furthermore, CH(3)SO(3)H and CF(3)SO(3)H were mixed with
      Bimps for comparison. Both systems showed a similar tendency, which differed from
      that of the HN(Tf)(2) system. The Tg decreased linearly with increasing acid
      content for every mixing ratio, while the ionic conductivity increased linearly.
      Proton transport properties in zwitterion/acid mixtures were strongly affected by
      the acid species added.

PMID- 21087028
TI  - Domain architecture of the DRpp29 protein and its interaction with the RNA
      subunit of Dictyostelium discoideum RNase P.
AB  - Dictyostelium discoideum nuclear RNase P is a ribonucleoprotein complex that
      displays similarities with its counterparts from higher eukaryotes such as the
      human enzyme, but at the same time it retains distinctive characteristics. In the
      present study, we report the molecular cloning and interaction details of DRpp29
      and RNase P RNA, two subunits of the RNase P holoenzyme from D. discoideum.
      Electrophoretic mobility shift assays exhibited that DRpp29 binds specifically to
      the RNase P RNA subunit, a feature that was further confirmed by the molecular
      modeling of the DRpp29 structure. Moreover, deletion mutants of DRpp29 were
      constructed in order to investigate the domains of DRpp29 that contribute to
      and/or are responsible for the direct interaction with the D. discoideum RNase P
      RNA. A eukaryotic specific, lysine- and arginine-rich region was revealed, which
      seems to facilitate the interaction between these two subunits. Furthermore, we
      tested the ability of wild-type and mutant DRpp29 to form active RNase P
      enzymatic particles with the Escherichia coli RNase P RNA.

PMID- 21087029
TI  - Cleavage of an RNA model catalyzed by dinuclear Zn(II) complexes containing rate
      accelerating pendants. Comparison of the catalytic benefits of H-bonding and
      hydrophobic substituents.
AB  - The transesterification of a simple RNA model, 2-hydroxypropyl p-nitrophenyl
      phosphate (2, HpNPP) promoted by seven dinuclear Zn(II) catalysts
      (3,4,5,6,7,8,9:Zn(II)2:(-OCH3)) based on the bis[bis(2-substituted-pyridinyl-6
      methyl)]amine ligand system was investigated in methanol under sspH-controlled
      conditions at 25.0 +/- 0.1  degrees C. The two metal complexing ligands were
      joined together via the amino N connected to a m-xylyl linker (3, 4, 5, 6, 7)
      where the 2-pyridinyl substituent = H, CH3, (CH)4, NH2, and NH(C?O)CH3,
      respectively, and a propyl linker (8, 9) where the ring substituent = H and CH3.
      All of the dinuclear complexes except 8:Zn(II)2 exhibit saturation kinetics for
      the kobs versus [catalyst] plots from which one can determine catalyst:substrate
      binding constants (KM), the catalytic rate constants for their decomposition
      (kcat), and the second order catalytic rate constants (k2cat = kcat/KM). In the
      case of 8:Zn(II)2, the plots of kobs versus [catalyst] as a function of sspH are
      linear, and the catalytic rate constants (k2cat) are defined as the gradients of
      the plots. Analysis of all of the data at the sspH optimum for each reaction
      indicates that the presence of the amino and acetamido H-bonding groups and the
      CH3 group provides similar increases of the kcat terms of 25-50 times that
      exhibited by the parent complex 3:Zn(II)2. However, in terms of substrate
      catalyst binding (KM), there is no clear trend that H-bonding groups or the CH3
      group provides stronger binding than the parent complex. In terms of the overall
      second order catalytic rate constant, the CH3, amino, and NH(C?O)CH3 groups
      provide 20, 10, and 68 times the k2cat observed for the parent complex. In the
      case of 9:Zn(II)2, the presence of the methyl groups provides a 1000-fold
      increase in activity (judged by k2cat) over the parent complex 8:Zn(II)2. The
      results are interpreted to indicate that H-bonding effects may be important for
      catalysis and less so for substrate binding, but the steric effect and impact on
      the local polarity provided by a methyl substituent is just as effective and in
      fact may form part of the acceleratory effect attributed to H-bonding in related
      systems.

PMID- 21087030
TI  - Thermal stability of 5-o-caffeoylquinic acid in aqueous solutions at different
      heating conditions.
AB  - Chlorogenic acid is a naturally occurring phenolic compound found in all higher
      plants. This component, being the ester of caffeic acid with quinic acid, is an
      important biosynthetic intermediate and plays an important role in the plant's
      response to stress. Potential uses of chlorogenic acid are suggested in
      pharmaceuticals, foodstuffs, feed additives, and cosmetics due to its recently
      discovered biomedical activity. This finding caused new interest in chlorogenic
      acid properties, its isomers, and its natural occurrence. It has been found that
      as many as nine compounds (chlorogenic acid derivatives and its reaction product
      with water) can be formed from 5-o-caffeoylquinic acid during the heating of its
      water solution. Three of them, two hydroxylated 5-o-caffeoylquinic acid
      derivatives and 4,5-dicaffeoylquinic acid, have been not reported, yet. The
      amount of each formed component depends on the heating time and temperature. The
      presented results are important for researchers investigating plant metabolism
      and looking for new plant components. The transformation product can be
      mistakenly treated as a new component, not found before in the examined plant, or
      can be a cause of erroneous quantitative estimations of plant composition.

PMID- 21087031
TI  - Cross-linking of hen egg white lysozyme by microbial transglutaminase under high
      hydrostatic pressure: localization of reactive amino acid side chains.
AB  - After incubation of hen egg white lysozyme (HEWL) with microbial transglutaminase
      (mTG) under high pressure (400-600 MPa for 30 min at 40  degrees C), the
      formation of HEWL oligomers was observed via SDS electrophoresis. At atmospheric
      pressure, HEWL represents no substrate for mTG. Likewise, enzymatic treatment
      following a pretreatment with high pressure did not lead to oligomerization.
      Reactive amino acid side chains were identified by peptide mapping after tryptic
      digestion using RP-HPLC with ESI-TOF-MS. Isopeptide-containing peptide fragments
      were found only in HEWL samples simultaneously treated with enzyme and pressure.
      It was found that mTG exclusively cross-links HEWL under high pressure by
      formation of an isopeptide between lysine at position 1 and glutamine at position
      121 in the peptide chain. Therefore, a pressure-induced partial and reversible
      unfolding of the protein with exposure of lysine and glutamine side chains has to
      occur, resulting in a site-directed oligomerization of HEWL by mTG. The enzymatic
      modification of HEWL by mTG under high pressure offers interesting perspectives
      for further functionalization reactions.

PMID- 21087032
TI  - Small molecule probes of cellular pathways and networks.
AB  - Small molecules are important not only as therapeutics to treat disease but also
      as chemical tools to probe complex biological processes. The discovery of novel
      bioactive small molecules has largely been catalyzed by screening diverse
      chemical libraries for alterations in specific activities in pure proteins assays
      or in generating cell-based phenotypes. New approaches are needed to close the
      vast gap between the ability to study either single proteins or whole cellular
      processes. This Review focuses on the growing number of studies aimed at
      understanding in more detail how small molecules perturb particular signaling
      pathways and larger networks to yield distinct cellular phenotypes. This type of
      pathway-level analysis and phenotypic profiling provides valuable insight into
      mechanistic action of small molecules and can reveal off-target effects and
      improve our understanding of how proteins within a pathway regulate signaling.

PMID- 21087035
TI  - Total synthesis of (+)-cymbodiacetal: a re-evaluation of the biomimetic route.
AB  - A total synthesis of (+)-cymbodiacetal (1) has been completed from (R)-(+)
      limonene oxide using a hetero-Diels-Alder cycloaddition as a key step. The key
      Diels-Alder cycloaddition proceeds with endo-selectivity (2:1, endo/exo) in
      quantitative yield, and the two diastereomeric spirochroman products are
      isolable, stable products. Furthermore, the exo- and the endo-hetero-Diels-Alder
      cycloaddition products (2 and 7) can be oxidized with m-CPBA to produce (+)
      cymbodiacetal (1) and the C(2)-symmetric bis-hemiacetal structure 8,
      respectively. The isomeric hemiacetal 9 is produced in both oxidation reactions.
      The structures of (+)-cymbodiacetal (1), its C(2)-symmetric diastereoisomer 8,
      and the isomeric hemiacetal 9 were confirmed using X-ray crystallography.

PMID- 21087034
TI  - Facile trypsin immobilization in polymeric membranes for rapid, efficient protein
      digestion.
AB  - Sequential adsorption of poly(styrene sulfonate) and trypsin in nylon membranes
      provides a simple, inexpensive method to create stable, microporous reactors for
      fast protein digestion. The high local trypsin concentration and short radial
      diffusion distances in membrane pores facilitate proteolysis in residence times
      of a few seconds, and the minimal pressure drop across the thin membranes allows
      their use in syringe filters. Membrane digestion and subsequent MS analysis of
      bovine serum albumin provide 84% sequence coverage, which is higher than the 71%
      coverage obtained with in-solution digestion for 16 h or the <50% sequence
      coverages of other methods that employ immobilized trypsin. Moreover, trypsin
      modified membranes digest protein in the presence of 0.05 wt % sodium dodecyl
      sulfate (SDS), whereas in-solution digestion under similar conditions yields no
      peptide signals in mass spectra even after removal of SDS. These membrane
      reactors, which can be easily prepared in any laboratory, have a shelf life of
      several months and continuously digest protein for at least 33 h without
      significant loss of activity.

PMID- 21087036
TI  - (4S,5S)-2,2,4-Triethyl-5-methyl-1,3-dioxolane: a new volatile released by a
      triatomine bug.
AB  - Adults of the triatomine bug Triatoma brasiliensis release 2,2,4-triethyl-5
      methyl-1,3-dioxolane (1) as a mixture of the (4S,5S)- and (4R,5R)-enantiomers in
      a ratio of 4:1. Among the volatile acetals identified from insects so far, this
      is the first example resulting from an intermolecular condensation of a carbonyl
      moiety and a diol substructure.

PMID- 21087038
TI  - Cross-reactivity of antibodies in some commercial deoxynivalenol test kits
      against some fusariotoxins.
AB  - Cross-reactivity of antibodies in AGRAQUANT, DON EIA, VERATOX, ROSA LF-DONQ, and
      MYCONTROLDON designed for deoxynivalenol (DON) determination in food and
      feedstuffs was evaluated against nivalenol, 3-acetylDON, 15-acetylDON, de-epoxy
      metabolite 1 of DON, DON-3beta-glucoside, T2-toxin, HT2-toxin, fusarenone X,
      diacetoxyscirpenol, verrucarol, and zearalenone. Cross-reactivity measurements
      were run in water using the 50% reduction of absorbance of the blank for ELISA
      kits or through direct DON determination upon using the standards of mycotoxins
      via ROSA LF-DONQ or MYCONTROLDON. For the tested toxin concentrations, all DON
      kits have low cross-reactivity toward diacetoxyscirpenol, T2-toxin, HT2-toxin,
      verrucarol, and zearalenone and moderate cross-reactivity toward 15-AcetylDON and
      fusarenone X. AGRAQUANT, DON EIA, and VERATOX kits showed high cross-reactivity
      in various ranking orders against DON-3-Glc, DOM-1, and 3AcDON. DON EIA showed
      also high cross-reactivity against nivalenol and fusarenone X. These mycotoxins
      could coexist in food or feedstuffs, and analytical results can be wrongly
      interpreted. Cross-reactivity does not allow checking the compliance with the
      legal norms, but it does allow an overall risk assessment for the consumers.
      Updating regularly the cross-reactivity evaluation of the produced batches is
      recommended for 3-acetylDON, nivalenol, DON-3-Glc, de-epoxy metabolite 1, and
      fusarenone X.

PMID- 21087037
TI  - Glycosyl alkoxythioimidates as complementary building blocks for chemical
      glycosylation.
AB  - It is reported that S-glycosyl O-methyl phenylcarbamothioates (SNea
      carbamothioates) have a fully orthogonal character in comparison to S
      benzoxazolyl (SBox) glycosides. This complete orthogonality was revealed by
      performing competitive glycosylation experiments in the presence of various
      promoters. The results obtained indicate that SNea carbamothioates have a very
      similar reactivity profile to that of glycosyl thiocyanates, yet are
      significantly more stable and tolerate selected protecting group manipulations.
      These features make the SNea carbamothioates new promising building blocks for
      further utilization in oligosaccharide synthesis.

PMID- 21087039
TI  - 2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 6-methoxy-benzoxazolin
      2-one (MBOA) levels in the wheat rhizosphere and their effect on the soil
      microbial community structure.
AB  - Despite increasing knowledge of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one
      (DIMBOA) and 6-methoxy-benzoxazolin-2-one (MBOA) as allelochemicals involved in
      the defense of wheat against pests, relatively little is known about their levels
      in the rhizosphere and interactions with the soil microbial community. This study
      quantified DIMBOA and MBOA in the wheat rhizosphere and analyzed the soil
      microbial community structure. MBOA rather than DIMBAO was found in the wheat
      rhizosphere, and its concentration varied with cultivars, plant densities, and
      growth conditions. Wheat could detect the presence of competing weeds and respond
      by increased MBOA in the rhizosphere. There was a linear positive relationship
      between the MBOA level in the wheat rhizosphere and soil fungi/bacteria. When
      DIMBOA was applied to soil, yielding MBOA increased soil fungi. There were
      different phospholipid fatty acid (PLFA) patterns in soil incubated with DIMBOA
      and MBOA. These results suggested that DIMBOA and MBOA could affect the soil
      microbial community structure to their advantage through the change in fungi
      populations.

PMID- 21087040
TI  - Rapid release and changing sources of Pb in a mountainous watershed during
      extreme rainfall events.
AB  - Although atmospheric Pb is known to accumulate in forest soils over time, little
      is known about the hydrologic Pb export from mountain forest soils. Short-term
      changes in Pb release and its sources during monsoon rainfall events were
      investigated in a mountainous watershed in the northern extreme of South Korea by
      combining intensive storm sampling with measurements of Pb concentrations and
      isotope ratios in soils and size-fractionated sediments. Biweekly monitoring of
      forest and agricultural streams showed relatively low dissolved Pb concentrations
      compared to those found in precipitation. Particulate Pb concentrations in both
      streams were higher than the dissolved concentrations and increased rapidly
      during rainfall events. Particulate Pb concentrations were substantially higher
      in the agricultural stream; the highest concentrations were associated with silt
      size sediment followed by sand. A comparison of (206)Pb/(207)Pb and
      (208)Pb/(206)Pb among sediment fractions and source soils indicated that major
      sources for silt- and sand-associated Pb in the agricultural stream change
      between streambank and cropland soils, whereas Pb in the forest stream is
      primarily derived from forest floors. The results suggest that Pb isotopes can be
      efficiently applied to tracing short-term changes in sediment and Pb sources and
      that extreme rainfall events can significantly increase Pb mobilization from
      erosion-prone mountain soils.

PMID- 21087041
TI  - Forward modeling of metal complexation by NOM: II. prediction of binding site
      properties.
AB  - An a priori model of metal complexation by natural organic matter (NOM) has
      previously been shown to predict experimental data at pH 7.0 and 0.1 M ionic
      strength (Cabaniss, S. E. Environ. Sci. Technol. 2009). Unlike macroscopic models
      based only on stoichiometry and thermodynamics, this a priori model also predicts
      the ligand groups and properties of complexed (occupied) molecules. Ligand
      molecules with strong binding sites form complexes at low metal concentrations
      and have average properties (molecular weight, charge, aromaticity) which can
      differ significantly from the average properties of bulk NOM. Cu(II), Ni(II) and
      Pb(II) preferentially bind to strong amine-containing sites which are often
      located on small (MW < 1000), lower-aromaticity molecules. Cd(II) and Zn(II) show
      generally weaker binding, although they also prefer amine-containing sites to
      pure carboxylates and bind to smaller, less aromatic molecules. Ca(II) shows no
      real preference for amine over carboxylate ligand groups, preferentially binding
      to larger and more negatively charged molecules. Al(III) has a unique preference
      for phenol-containing sites and larger, more aromatic molecules. While some
      predictions of this model are consistent with a variety of experimental data from
      the literature, others await validation by molecular-level analysis.

PMID- 21087043
TI  - Gold(I)-catalyzed intramolecular tandem addition/Friedel-Crafts reactions between
      acyclic enamides and 1-arylalkynes.
AB  - Electron-deficient acyclic enamine derivatives react with electron-rich 1
      arylalkynes using cationic gold(I) species as catalysts in an intramolecular
      process to form annulated 1-amido-substituted indene derivatives as the major
      products. Yields for this process range between 21% and 98%. In some cases, a two
      step process that includes a subsequent alkene isomerization is needed.

PMID- 21087042
TI  - Carbon and nitrogen natural stable isotopes in Slovene honey: adulteration and
      botanical and geographical aspects.
AB  - Isotope parameters (delta(13)C(honey), delta(13)C(protein), delta(15)N) were
      determined for 271 honey samples of 7 types (black locust, multifloral, lime,
      chestnut, forest, spruce, and fir honeys) from 4 natural geographical regions of
      Slovenia. Carbon and nitrogen stable isotope ratios were measured to elucidate
      the applicability of this method in the identification of the botanical and
      geographical origin of honey and in honey adulteration. Only 2.2% of the samples
      were adulterated according to the internal standard carbon isotope ratio analysis
      method. Botanical origin did not have any major influence on the honey isotope
      profiles; only black locust honey showed higher delta(13)C values. Some
      differences were seen across different production years, indicating that the
      influence of season should be further tested. Statistical and multivariate
      analyses demonstrated differences among honeys of various geographical origins.
      Those from the Alpine region had low delta(13)C (-26.00/00) and delta(15)N values
      (1.10/00); those from the Mediterranean region, high delta(13)C (-24.60/00) and
      medium delta(15)N values (2.20/00); those from the Pannonian region, medium
      delta(13)C (-25.60/00) and high delta(15)N value (3.00/00); and those from the
      Dinaric region, medium delta(13)C (-25.70/00) and low delta(15)N values
      (1.40/00).

PMID- 21087044
TI  - Remote stereoinduction in the acylation of fully substituted enolates: tandem
      Reformatsky/quaternary Claisen condensations of silyl glyoxylates and beta
      lactones.
AB  - Reformatsky reagents react sequentially with silyl glyoxylates and beta-lactones
      to give highly functionalized Claisen condensation products. A heretofore
      undocumented instance of stereochemical 1,4-induction results in efficient
      transmission of beta-lactone stereochemistry to the emerging fully substituted
      stereocenter. Second-stage transformations reveal that the five heteroatom
      containing functionalities embedded within the products are entirely chemo
      differentiated, a circumstance that permits rapid assembly of the leustroducsin B
      core substructure.

PMID- 21087045
TI  - Relationship between endogenous protein disulfide isomerase family proteins and
      glutenin macropolymer.
AB  - The effects of endogenous protein disulfide isomerase (PDI) family proteins on
      the properties of gluten proteins in dough during breadmaking were determined
      using bacitracin, an inhibitor of PDI. Bread loaf volume in the presence of
      bacitracin was increased to 118% of that in the absence of bacitracin. The
      addition of bacitracin caused a decrease in the extension tolerance of the dough.
      The amount of sodium dodecyl sulfate (SDS)-insoluble glutenin macropolymer (GMP)
      in dough decreased to approximately 70% of that in flour during the 20 min of
      mixing for doughmaking. The addition of bacitracin to dough caused a dramatic GMP
      decrease, corresponding to ~20-30% of that in flour during the 20 min of mixing.
      The decrease in GMP was compensated by an increase in SDS-soluble glutenin
      polymer. Taken together, these results suggest that the endogenous PDI family
      proteins in flour suppress the depolymerization of GMP during dough mixing.

PMID- 21087046
TI  - Isobaric labeling approach to the tracking and relative quantitation of peptide
      damage at the primary structural level.
AB  - Protein oxidative damage lies behind skin and hair degradation and the
      deterioration of protein-based products, such as wool and meat, in addition to a
      range of serious health problems. Effective strategies to ameliorate degenerative
      processes require detailed fundamental knowledge of the chemistry at the
      molecular level, including specific residue-level products and their relative
      abundance. This paper presents a new means of tracking damage-induced side-chain
      modification in peptides using a novel application for isobaric label
      quantification. Following exposure to heat and UVA and UVB irradiation,
      tryptophan and tyrosine damage products in synthetic peptides were characterized
      and tracked using ESI-MS/MS and iTRAQ labeling-based relative quantification. An
      in-depth degradation profile of these peptides was generated, enabling the
      formation of even low-abundance single-residue-level modifications to be
      sensitively monitored. The development of this novel approach to profiling and
      tracking residue-level protein damage offers significant potential for
      application in the development and validation of protein protection treatments.

PMID- 21087047
TI  - DRIFT study on cerium-tungsten/titania catalyst for selective catalytic reduction
      of NOx with NH3.
AB  - CeO(2)/TiO(2) and CeO(2)-WO(3)/TiO(2) catalysts prepared by impregnation method
      assisted with ultrasonic energy were investigated on the selective catalytic
      reduction (SCR) of NO(x) (NO and NO(2)) by NH(3). The catalytic activity of 10%
      CeO(2)/TiO(2) (CeTi) was greatly enhanced by the addition of 6% WO(3) in the
      broad temperature range of 200-500  degrees C, the promotion mechanism was
      proposed on basis of the results of in situ diffuse reflectance infrared
      transform spectroscopy (DRIFT). When NH(3) was introduced into both catalysts
      preadsorbed with NO + O(2), SCR would not proceed except for the reaction between
      NO(2) and ammonia. For CeO(2)/TiO(2) catalysts, coordinated NH(3) linked to Lewis
      acid sites were the main adsorbed ammonia species. When NO + O(2) was introduced,
      all the ammonia species consumed rapidly, indicating that these species could
      react with NO(x) effectively. Two different reaction routes, L-H mechanism at low
      temperature (<200  degrees C) and E-R mechanism at high temperatures (>200 
      degrees C), were presented for SCR reaction over CeO(2)/TiO(2) catalyst. For
      CeO(2)-WO(3)/TiO(2) catalysts, the Lewis acid sites on Ce(4+) state could be
      converted to Bronsted acid sites due to the unsaturated coordination of Ce(n+)
      and W(n+) ions. When NO + O(2) was introduced, the reaction proceeded more
      quickly than that on CeO(2)/TiO(2). The reaction route mainly followed E-R
      mechanism in the temperature range investigated (150-350  degrees C) over CeO(2)
      WO(3)/TiO(2) catalysts. Tungstation was beneficial for the formation of Ce(3+),
      which would influence the active sites of the catalyst and further change the
      mechanisms of SCR reaction. In this way, the cooperation of tungstation and the
      presence of Ce(3+) state resulted in the better activity of CeO(2)-WO(3)/TiO(2)
      compared to that of CeO(2)/TiO(2).

PMID- 21087048
TI  - Abiotic reduction of pendimethalin and trifluralin in controlled and natural
      systems containing Fe(II) and dissolved organic matter.
AB  - The environmental fate of dinitroaniline herbicides is poorly understood, despite
      their classification as Persistent Bioaccumulative Toxins by the U.S.
      Environmental Protection Agency. This study investigated the abiotic reduction of
      pendimethalin and trifluralin in controlled laboratory systems in the presence of
      Fe(II) and fulvic acids isolated from various surface waters and in sediment pore
      waters containing naturally abundant levels of dissolved Fe(II) and dissolved
      organic matter (DOM). It was found that Fe(II) was necessary for pendimethalin
      and trifluralin reduction to occur in controlled systems and that higher
      concentrations of DOM slowed Fe(II)-mediated reactions. Pendimethalin and
      trifluralin reduction in natural pore waters was roughly an order of magnitude
      slower compared to controlled Fe(II)-DOM solutions, indicating that the reactive
      Fe(II) species responsible for reduction are concentration-limited in natural
      pore waters relative to controlled systems. The results show that caution must be
      exercised when extrapolating results from controlled system reactions to natural
      systems and that abiotic reduction of both trifluralin and pendimethalin is
      observed within 3-7 days in anaerobic sedimentary pore waters containing high
      concentrations of both dissolved Fe(II) and DOM.

PMID- 21087049
TI  - Flexible low-voltage organic thin-film transistors enabled by low-temperature,
      ambient solution-processable inorganic/organic hybrid gate dielectrics.
AB  - We report here on the design, synthesis, processing, and dielectric properties of
      novel cross-linked inorganic/organic hybrid blend (CHB) dielectric films which
      enable low-voltage organic thin-film transistor (OTFT) operation. CHB thin films
      (20-43 nm thick) are readily fabricated by spin-coating a zirconium chloride
      precursor plus an alpha,omega-disilylalkane cross-linker solution in ambient
      conditions, followed by curing at low temperatures (~150  degrees C). The very
      smooth CHB dielectrics exhibit excellent insulating properties (leakage current
      densities ~10(-7) A/cm(2)), tunable capacitance (95-365 nF/cm(2)), and high
      dielectric constants (5.0-10.2). OTFTs fabricated with pentacene as the organic
      semiconductor function well at low voltages (<-4.0 V). The morphologies and
      microstructures of representative semiconductor films grown on CHB dielectrics
      prepared with incrementally varied compositions and processing conditions are
      investigated and shown to correlate closely with the OTFT response.

PMID- 21087050
TI  - Macromolecular inhibition of quorum sensing: enzymes, antibodies, and beyond.

PMID- 21087051
TI  - Research in olive oil: challenges for the near future.
AB  - Olive oil, a traditional food product with thousands of years of history, is
      continually evolving toward a more competitive global market. Being one of the
      most studied foods across different disciplines, olive oil still needs intensive
      research activity to face some vulnerabilities and challenges. This perspective
      describes some of them and shows a vision of research on olive oil for the near
      future, bringing together those aspects that are more relevant for better
      understanding and protection of this edible oil. To accomplish the most urgent
      challenges, some possible strategies are outlined, taking advantage of the latest
      analytical advances, considering six areas: (i) olive growing; (ii) processing,
      byproduct, and environmental issues; (iii) virgin olive oil sensory quality; (iv)
      purity, authentication, and traceability; (v) health and nutrition; (vi)
      consumers. The coming research, besides achieving those challenges, would
      increase the understanding of some aspects that are still the subject of debate
      and controversy among scientists focused on olive oil.

PMID- 21087052
TI  - Synthesis of stilbene and distyrylbenzene derivatives through rhodium-catalyzed
      ortho-olefination and decarboxylation of benzoic acids.
AB  - Ortho-substituted benzoic acids efficiently undergo precisely ordered ortho
      olefination/decarboxylation upon treatment with styrenes in the presence of a
      rhodium catalyst and silver salt oxidant to afford the corresponding meta
      substituted stilbene derivatives. The selective syntheses of 1,3- and 1,4
      distyrylbenzenes have also been realized through the reactions of simple benzoic
      acid and phthalic acid, respectively, with styrene under similar conditions.

PMID- 21087055
TI  - H-shaped oligothiophenes with low band gaps and amphoteric redox properties.
AB  - H-shaped bridged oligothiophenes HT-1 and HT-2 were synthesized by two different
      approaches. Different from normal oligothiophenes, HT-1 and HT-2 showed low band
      gaps and amphoteric redox behaviors due to intramolecular charge transfer, which
      is further supported by time-dependent DFT calculations.

PMID- 21087054
TI  - Quantum dot and Cy5.5 labeled nanoparticles to investigate lipoprotein
      biointeractions via Forster resonance energy transfer.
AB  - The study of lipoproteins, natural nanoparticles comprised of lipids and
      apolipoproteins that transport fats throughout the body, is of key importance to
      better understand, treat, and prevent cardiovascular disease. In the current
      study, we have developed a lipoprotein-based nanoparticle that consists of a
      quantum dot (QD) core and Cy5.5 labeled lipidic coating. The methodology allows
      judicious tuning of the QD/Cy5.5 ratio, which enabled us to optimize Forster
      resonance energy transfer (FRET) between the QD core and the Cy5.5-labeled
      coating. This phenomenon allowed us to study lipoprotein-lipoprotein
      interactions, lipid exchange dynamics, and the influence of apolipoproteins on
      these processes. Moreover, we were able to study HDL-cell interactions and
      exploit FRET to visualize HDL association with live macrophage cells.

PMID- 21087056
TI  - Synthetic development and mechanistic study on Pd(II)-catalyzed cyclization of
      enediynes to benzo[a]carbazoles.
AB  - Treatment of N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines (1) with 10 mol
      % of palladium chloride and 2 equiv of cupric chloride in refluxing THF gave
      benzo[a]carbazoles (6) in good yields. A mechanistic study showed that this
      reaction must proceed through formation of haloindole (7) followed by a
      palladium(II)-catalyzed atom transfer cyclization reaction to give the
      benzo[a]carbazoles.

PMID- 21087057
TI  - Metabolomic approach with LC-QTOF to study the effect of a nutraceutical
      treatment on urine of diabetic rats.
AB  - The rat treated with streptozotocin has been proposed as the most appropriate
      model of systemic oxidative stress for studying antioxidant therapies. In that
      sense, rosemary extracts have long been recognized as having antioxidant
      properties, and folic acid may be able to improve endothelial progenitor cell
      function. A mixture containing both has been tested as a possible nutraceutical
      to improve health complications in diabetes. We have developed the methodology to
      evaluate metabolic changes in the urine of streptozotocin-induced diabetic rats
      after supplementing their diet with rosemary extract obtained with supercritical
      fluids (SFE) containing 10% folic acid in an acute but short-term study. It has
      been done with a metabolomics approach using LC-QTOF as an analytical tool. About
      20 endogenous metabolites have been identified by databases and MS/MS showing
      statistically significant changes. Among them, several amino acids and their
      metabolites point to changes due to the effect of the gut microbiota. In
      addition, the comparison between control and streptozotocin-diabetic rats has
      permitted the showing of some metabolic coincidences between type 1 diabetes and
      other (possible) autoimmune diseases such as autism and/or Crohn's disease, and
      the nutraceutical intervention has succeeded in inducing changes in such
      biomarkers.

PMID- 21087058
TI  - In silico calculation of acidity constants of carbonic acid conformers.
AB  - In order to explore the aqueous acid chemistry of carbonic acid, we employ a
      constrained ab initio molecular dynamics (AIMD) technique to study acid
      dissociations of its three conformers including CC (cis-cis), CT (cis-trans), and
      TT (trans-trans). The simulations of reagent states reveal similar hydration
      characteristics for them: the hydroxyls donate H-bonds to solvating waters but no
      obvious H-bonding exists between hydroxyl oxygen atoms and waters. It is found
      that the CC conformer dissociates spontaneously to bicarbonate within picoseconds
      whereas the other two can stay for relatively long simulation times. This
      suggests that CC has the strongest acidity among the three conformers and it is
      not stable in water. The simulations indicate that the symmetrical hydroxyls of
      TT conformer have a pKa value of 3.11 and the two asymmetrical hydroxyls of CT
      show different pKa values: 2.60 and 3.75, respectively. Overall, these results
      confirm the recent experimental measurement: about 4.0 for deuterated carbonic
      acid. By analyzing the dissociation processes, it is revealed that the
      differences of the acid constants stem from the initial steps of hydroxyls
      stretches. This simulation study provides a quantitative and microscopic basis
      for better understanding the reactivity of aqueous carbonate species.

PMID- 21087059
TI  - pH effect on the photochemistry of 4-methylcoumarin phosphate esters: caged
      phosphate case study.
AB  - There are numerous reports of coumarin ester derivatives, in particular phosphate
      esters, as photocleavable cages in biological systems. Despite the comprehensive
      analysis of the photocleavage mechanism, studies of 4-methylcoumarin caged
      phosphates and/or nucleotides were always performed at constant pH. In this work,
      we present the study of the pH effect on the photochemistry of (7
      diethylaminocoumarin-4-yl)methyl phosphate (DEACM-P). Fluorescence and
      photocleavage quantum yields, as well as the fluorescence decay times were
      measured as a function of the pH. It was found that the pH produces significant
      changes in the overall photochemical quantum yield of DEACM-P, and the observed
      changes are complementary to those obtained from the fluorescence quantum yield.
      Deprotonation of DEACM-HPO(4)(-) to yield DEACM-PO(4)(2-), produces a decrease in
      the photochemical quantum yield (from 0.0045 to 0.0003) and an increase in the
      fluorescence quantum yield (from 0.072 to 0.092). Moreover, from the analysis of
      the decay times, we have also found that hydroxyl ion is not only relevant, but
      it is mechanistically involved in the photoreaction of DEACM-HPO(4)(-).

PMID- 21087060
TI  - Investigation on the inclusions of PCB52 with cyclodextrins by performing DFT
      calculations and molecular dynamics simulations.
AB  - The effective enrichment and identification of lowly concentrated polychlorinated
      biphenyls (PCBs) in the environment is attracting enormous research attention due
      to human health concerns. Cyclodextrins (CDs) are known to be capable of forming
      inclusion complexes with a variety of organic molecules. The purpose of this
      study is to provide theoretical evidence of whether CDs as host molecules can
      include the guest molecules PCBs to form stable host-guest inclusion complexes,
      and if so, whether the general infrared and Raman techniques are suitable for the
      direction of CD-modified PCBs. Focusing on a representative PCB molecule,
      2,2',5,5'-tetrachlorobiphenyl (PCB52), we carried out density functional theory
      calculations and molecular dynamics (MD) simulations on its complexes with alpha
      , beta-, and gamma-CDs with different host-guest stoichiometry ratios, including
      1:1, 1:2, 2:1, and 2:2. On the basis of both the optimized geometries and
      calculated energy changes raised from encapsulating the guest molecule into the
      cavities of CDs, the CDs are believed to be suitable hosts for accommodating
      PCB52 guest molecules. The stability of inclusion complexes depends on both the
      type of CD and host-guest stoichiometry ratio. MD simulations give a clear
      picture of the scene on how the PCB52 molecule enters the cavity of beta-CD. The
      vibrational analyses on the 1:1 complexes of CDs provide information for the
      spectral characterization of the inclusion complexes: Raman spectroscopy can
      deliver the characteristic bands of PCB52, whereas IR spectroscopy cannot
      uniquely assign them, implying that Raman spectroscopy is a useful technique for
      the identification of CD-modified PCBs. The present theoretical results are
      expected to provide guidance for the relevant experimental research.

PMID- 21087061
TI  - Photoelectron imaging and theoretical studies of group 11 cyanides MCN (M = Cu,
      Ag, Au).
AB  - Photodetachment of group 11 cyanide anions MCN(-) (M = Cu, Ag, Au) has been
      investigated using photoelectron velocity-map imaging. The electron affinities
      (EAs) of CuCN (1.468(26)) and AgCN (1.602(22)) are larger, while that of AuCN
      (2.066(8)) is smaller than those of the free atoms. This intriguing observation
      was confirmed by theoretical studies and was assigned to the transition between
      ionic and covalent bond properties. The harmonic frequencies of the extended
      vibrational progressions in the M-C stretching mode are 460(50), 385(27), and
      502(10) cm(-1), respectively, which suggests a stronger bond for Au-CN than for
      Ag-CN. Electronic structure analysis and model calculations suggest that all M-C
      bonds in group 11 cyanides are best described as single bonds. A model has been
      proposed to explain how the relativistic effects influence the Au-C bond strength
      in AuCN.

PMID- 21087062
TI  - A theoretical study on small iridium clusters: structural evolution, electronic
      and magnetic properties, and reactivity predictors.
AB  - The structural, electronic, and magnetic properties of iridium clusters with
      sizes of n = 2-15 are investigated by employing the generalized gradient
      approximation of density functional theory. Simple cube evolution pattern is
      revealed for Ir(2-15) clusters, as predicted by previous reports. It is
      remarkable that for Ir(10), Ir(11) clusters, new generated isomers with higher
      stabilities relative to those reported in previous studies are obtained. The even
      sized clusters are more stable than the odd-sized species. The Ir-Ir bonds in the
      cubic Ir(8) and Ir(12) clusters, which are considered as the basic units in the
      structural evolution present covalent character. Starting from n = 8, the
      magnetic moments of Ir(n) clusters decrease sharply. The moments of magnetic
      clusters show 5d characters. The reactive site selectivity of studied clusters
      with n = 5-15 is analyzed with condensed Fukui function. The capped atoms in
      certain clusters (Ir(9), Ir(10), Ir(11), and Ir(13)) generally show extraordinary
      activity for both nucleophilic and electrophilic attack.

PMID- 21087063
TI  - Experimental and computational thermochemical study of alpha-alanine (DL) and
      beta-alanine.
AB  - This paper reports an experimental and theoretical study of the gas phase
      standard (p degrees  = 0.1 MPa) molar enthalpies of formation, at T = 298.15 K,
      of alpha-alanine (DL) and beta-alanine. The standard (p degrees  = 0.1 MPa) molar
      enthalpies of formation of crystalline alpha-alanine (DL) and beta-alanine were
      calculated from the standard molar energies of combustion, in oxygen, to yield
      CO2(g), N2(g), and H2O(l), measured by static-bomb combustion calorimetry at T =
      298.15 K. The vapor pressures of both amino acids were measured as function of
      temperature by the Knudsen effusion mass-loss technique. The standard molar
      enthalpies of sublimation at T = 298.15 K was derived from the Clausius-Clapeyron
      equation. The experimental values were used to calculate the standard (p degrees 
      = 0.1 MPa) enthalpy of formation of alpha-alanine (DL) and beta-alanine in the
      gaseous phase, Delta(f)H(m) degrees (g), as -426.3 +/- 2.9 and -421.2 +/- 1.9
      kJ.mol(-1), respectively. Standard ab initio molecular orbital calculations at
      the G3 level were performed. Enthalpies of formation, using atomization
      reactions, were calculated and compared with experimental data. Detailed
      inspections of the molecular and electronic structures of the compounds studied
      were carried out.

PMID- 21087065
TI  - Comparison of published explicit criteria for potentially inappropriate
      medications in older adults.
AB  - Several sets of explicit criteria for potentially inappropriate medications
      (PIMs) have been developed by expert consensus. The purpose of this review is to
      summarize and compare existing criteria to enable more informed choices about
      their use. After a systematic literature search was conducted, seven examples of
      criteria published between 1991 and 2009 were included in the review and their
      individual characteristics are presented. Common medications listed in the
      majority of these criteria are also summarized. PIMs listed regardless of co
      morbidities in all seven criteria sets were long-acting benzodiazepines and
      tricyclic antidepressants. PIMs regardless of co-morbidities were most similar
      among the Beers, Rancourt and Winit-Watjana criteria. Several drug-disease
      interactions such as benzodiazepines and falls were cited in most criteria. With
      respect to drug-drug interactions, most criteria agreed that concomitant use of
      warfarin and NSAIDs should be avoided. The prevalence of PIMs varied with patient
      population, availability of medications in local markets, the specialties of the
      prescribing physicians and the assessment instruments used. The associations
      between PIMs use and health outcomes were largely inconclusive because of limited
      data. Further research is necessary to validate these published criteria in terms
      of reducing the incidence of adverse drug reactions and improving health outcomes
      among older adults. Incorporation of these criteria into computer-assisted order
      entry systems would increase their utilization in daily practice.

PMID- 21087067
TI  - Botanical extracts as anti-aging preparations for the skin: a systematic review.
AB  - Although topical creams and other anti-aging products purport to reduce the
      appearance of aging and skin wrinkling, there has been no critical analysis in
      the scientific literature of their effectiveness. This systematic review
      critically evaluates the evidence for the effectiveness or efficacy of botanical
      treatments in reducing skin aging and wrinkling. MEDLINE, Embase, CINAHL(r),
      CENTRAL and AMED databases were searched from their inception until October 2009.
      Reference lists of retrieved articles were hand-searched. Manufacturers and
      professional associations were contacted in order to identify further non
      published studies. No language restrictions were applied. Only randomized
      clinical trials or controlled clinical trials assessing the effectiveness of
      botanical extracts in reducing wrinkling and aging of the skin were included.
      Data were extracted by two independent reviewers and methodological quality was
      assessed using the Jadad score and key aspects of the Cochrane risk of bias tool.
      Of 36 potentially relevant studies, 11 trials of botanical extracts for reducing
      skin wrinkling and the appearance of aging met all the inclusion criteria. No
      trials were identified following contact with anti-aging and cosmetic
      organizations, companies and professional bodies. A significant reduction in skin
      wrinkling was noted for date kernel extract, cork extract, soy extract, Rosaceae
      and peony extract. No significant reduction was noted for green tea,
      Vitaphenol(r) (a combination of green and white teas, mangosteen and pomegranate
      extract) or maca root. All trials were of poor methodological quality. Adverse
      effects were frequently not reported. In summary, there is some weak evidence to
      suggest that several botanical extracts may be effective in reducing the
      appearance of skin aging but no evidence that this effect is enduring.
      Independent replications with larger, more diverse samples, longer treatment
      durations and more rigorous study designs are required to validate these
      preliminary findings.

PMID- 21087066
TI  - Lipid lowering for secondary prevention of cardiovascular disease in older
      adults.
AB  - A perceived lack of evidence for benefit and safety concerns may lead to
      underprescription of HMG-CoA reductase inhibitors (statins) in older adults. This
      article reviews clinical data regarding the effect of lipid-lowering therapies on
      cardiovascular outcomes in older adults with a focus on secondary prevention and
      safety considerations in this population. A literature search of the PubMed
      database (January 1984 to April 2009) was performed using search terms that
      included: 'aged' (MeSH heading), 'elderly', 'anticholesteremic agents',
      'antilipemic agents', 'hydroxymethylglutaryl-CoA reductase inhibitors',
      'cardiovascular diseases', 'randomized controlled trial', 'meta-analysis' and
      'drug safety'. Results from large, randomized, controlled trials show that statin
      therapy lowers both all-cause and coronary heart disease mortality and reduces
      myocardial infarction, stroke and the need for revascularization in individuals
      aged >=65 years who have a history of coronary heart disease. Given the high rate
      of recurrent cardiovascular events in older adults, there is substantial
      potential for statin treatment to provide benefits in this population. When older
      patients are prescribed statins, attention should be given to potential drug
      interactions, age-related changes in drug pharmacokinetics, adverse effects such
      as myopathy and risks arising from co-morbid conditions. Additional studies on
      the benefits and risks of lipid-lowering therapy in individuals aged >=70 years
      who have no history of cardiovascular disease, and particularly in those aged
      >=80 years, are needed. Other available lipid-modifying drugs - bile acid
      sequestrants (bile acid binding protein modulators), ezetimibe, niacin and
      fibrates (fibric acid derivatives) - may be required in patients who are statin
      intolerant or have mixed dyslipidaemia, or in whom standard doses of statins may
      not be sufficient to achieve low-density lipoprotein cholesterol goals.

PMID- 21087068
TI  - Prevalence and predictors of anticholinergic medication use in elderly nursing
      home residents with dementia: analysis of data from the 2004 National Nursing
      Home Survey.
AB  - BACKGROUND: Medications with anticholinergic properties are frequently used in
      the elderly population. However, evidence suggests that these medications are
      associated with significant adverse effects and may lead to worsening of
      cognitive impairment, particularly in elderly patients with dementia. OBJECTIVE:
      To examine the utilization of anticholinergic medications and factors associated
      with anticholinergic medication use in elderly nursing home patients with
      dementia. METHODS: The study examined anticholinergic medication utilization for
      patients aged >=65 years with dementia, using the 2004 US National Nursing Home
      Survey (NNHS) data. Anticholinergic drugs were identified using the
      Anticholinergic Drug Scale (ADS), which classifies anticholinergic drugs into
      four levels in increasing order of their anticholinergic activity. Descriptive
      analysis was conducted using sampling weights to determine the prevalence of
      anticholinergic medication use. Multiple logistic regression within the
      conceptual framework of the Andersen Behavioral Model was used to examine the
      factors associated with anticholinergic medication use in the study population.
      Use of medications with marked anticholinergic activities (ADS level 2 or 3) was
      the dependent variable, and independent variables were the various predisposing,
      enabling and need factors. RESULTS: According to the 2004 NNHS, 509,931 (95% CI
      490,160, 529,702) or 73.62% (95% CI 72.23, 75.00) of elderly patients with
      dementia used anticholinergic medications. The highest prevalence of
      anticholinergic medication use among elderly patients with dementia was seen for
      level-1 medications (67.96%; 95% CI 66.51, 69.41), and 21.27% (95% CI 19.93,
      22.60) used ADS level-2 or level-3 medications. Multivariate regression analysis
      showed that the predisposing factor of age was negatively associated with the use
      of medications with marked anticholinergic activities (ADS level 2 or 3) and the
      enabling factor of Medicaid as the source of payment increased the likelihood of
      receiving these higher-level anticholinergics. Among the need factors, dependence
      in decision-making ability and behavioural symptoms decreased the likelihood of
      receiving higher-level anticholinergics, whereas factors such as total number of
      medications, depressed mood indicators and diagnoses of schizophrenia, anxiety
      and Parkinson's disease increased the likelihood of use of such medications.
      CONCLUSIONS: Over one in five elderly nursing home residents with dementia used
      medications with marked anticholinergic activities. The study findings suggest
      the need to optimize the use of anticholinergic medications in vulnerable
      patients with dementia given the potentially severe adverse cognitive effects of
      these agents.

PMID- 21087069
TI  - Older women's views about prescription osteoporosis medication: a cross
      sectional, qualitative study.
AB  - BACKGROUND: Osteoporosis is a significant health problem, especially for older
      women. Prescription osteoporosis medication can reduce fractures, but many women
      do not accept treatment or discontinue treatment before benefits are achieved.
      OBJECTIVES: To explore older women's views about prescription osteoporosis
      medication use in depth and to identify specific beliefs and experiences that
      influence these views. METHODS: We conducted in-depth telephone interviews with
      women aged >=65 years with clinically confirmed osteoporosis. Interviewees were
      asked about their beliefs and experiences related to osteoporosis and
      osteoporosis treatment. Interviews were recorded and transcribed; key themes were
      identified using qualitative analysis. RESULTS: Perceived need, medication
      effectiveness and medication safety were identified as critical influences on
      women's views about prescription osteoporosis medication. These perceptions were
      in turn influenced by various beliefs, experiences and behaviours, including
      interactions with the physician, personal experience and behaviours, and
      vicarious experience. CONCLUSIONS: Older women with osteoporosis need clear
      information about their condition, including the diagnosis, the implications of
      the diagnosis, treatment options, medication effectiveness and side effects.
      Physicians should check with their patients to confirm understanding and address
      concerns, as older women may not always voice their reservations and concerns.

PMID- 21087070
TI  - Reduction of inappropriate medications among older nursing-home residents: a
      nurse-led, pre/post-design, intervention study.
AB  - BACKGROUND: Medication-related problems are common in the growing population of
      older adults and inappropriate prescribing is a preventable risk factor. Explicit
      criteria such as the Beers criteria provide a valid instrument for describing the
      rate of inappropriate medication (IM) prescriptions among older adults.
      OBJECTIVE: To reduce IM prescriptions based on explicit Beers criteria using a
      nurse-led intervention in a nursing-home (NH) setting. STUDY DESIGN: The pre/post
      design included IM assessment at study start (pre-intervention), a 4-month
      intervention period, IM assessment after the intervention period (post
      intervention) and a further IM assessment at 1-year follow-up. SETTING: 204-bed
      inpatient NH in Bern, Switzerland. PARTICIPANTS: NH residents aged >=60 years.
      INTERVENTION: The intervention included four key intervention elements: (i)
      adaptation of Beers criteria to the Swiss setting; (ii) IM identification; (iii)
      IM discontinuation; and (iv) staff training. MAIN OUTCOME MEASURE: IM
      prescription at study start, after the 4-month intervention period and at 1-year
      follow-up. RESULTS: The mean +/- SD resident age was 80.3 +/- 8.8 years.
      Residents were prescribed a mean +/- SD 7.8 +/- 4.0 medications. The prescription
      rate of IMs decreased from 14.5% pre-intervention to 2.8% post-intervention
      (relative risk [RR] = 0.2; 95% CI 0.06, 0.5). The risk of IM prescription
      increased nonstatistically significantly in the 1-year follow-up period compared
      with post-intervention (RR = 1.6; 95% CI 0.5, 6.1). CONCLUSIONS: This
      intervention to reduce IM prescriptions based on explicit Beers criteria was
      feasible, easy to implement in an NH setting, and resulted in a substantial
      decrease in IMs. These results underscore the importance of involving nursing
      staff in the medication prescription process in a long-term care setting.

PMID- 21087071
TI  - Prevalence and risk of polypharmacy among the elderly in an outpatient setting: a
      retrospective cohort study in the Emilia-Romagna region, Italy.
AB  - BACKGROUND: Polypharmacy, the simultaneous taking of many medications, has been
      well documented and is a topic of much concern for those looking to improve the
      quality of care for the elderly. Elderly patients often develop complicated and
      multifactorial health states that require extensive pharmacotherapy, leaving this
      population at risk for exposure to drug-drug interactions and other adverse
      events. Previous literature supports an association between an increase in the
      rate of adverse events as the number of drugs taken by a patient increases.
      OBJECTIVE: We sought to evaluate the prevalence of polypharmacy, and to determine
      patient characteristics that are predictive of exposure to polypharmacy, in the
      elderly population of the Emilia-Romagna region in Italy. METHODS: We conducted a
      retrospective cohort study of the 2007 Emilia-Romagna outpatient pharmacy
      database linked with patient information available from a demographic file of
      approximately 1 million Emilia-Romagna residents aged >=65 years. The cohort
      comprised 887,165 elderly subjects who had at least one prescription filled
      during the study year. Using the WHO's defined daily dose (DDD) to determine the
      duration of treatment for a given drug, we defined a polypharmacy episode as
      overlapping treatment with five or more medications occurring for at least 1 day.
      The prevalence of polypharmacy was measured together with subject characteristics
      found to be predictive of polypharmacy exposure. RESULTS: A total of 349,689
      elderly people in the population (39.4%) were exposed to at least one episode of
      polypharmacy during the study period. The prevalence of polypharmacy
      substantially increased with age and with a higher number of chronic conditions.
      Over 35% of those exposed to polypharmacy were exposed for 101 or more days of
      the year. The top three classes of medications involved in polypharmacy were
      antithrombotics, peptic ulcer disease and gastro-oesophageal reflux disease
      agents, and ACE inhibitors. The odds of exposure to polypharmacy were higher for
      older subjects, males and subjects living in urban areas. CONCLUSIONS: This study
      provides evidence that the prevalence of polypharmacy in the elderly in Emilia
      Romagna is substantial. Educational programmes should be developed to inform
      clinicians about the magnitude of the polypharmacy phenomenon and the patient
      characteristics associated with polypharmacy. Raising physicians' awareness of
      polypharmacy may help to ensure safe, effective and appropriate use of medication
      in the elderly.

PMID- 21087072
TI  - Computerized alert reduced D-dimer testing in the elderly.
AB  - OBJECTIVE: To assess the effect of a targeted age-specific computerized alert to
      reduce D-dimer testing in elderly patients. STUDY DESIGN: A single-crossover
      cluster randomized trial of computerized alerts during physician order entry
      involving 8 ambulatory care clinics in a group-model integrated care delivery
      system. METHODS: The rate of completed D-dimer tests per 1000 patient visits,
      ratio of completed venous ultrasonography to completed D-dimer tests, and rate of
      completed venous ultrasonography per 1000 patient visits. RESULTS: The rate of
      completed D-dimer tests per 1000 visits among patients 65 years and older in
      intervention clinics decreased from 5.02 to 1.52 (95% confidence interval [CI], 
      4.20 to -2.80; P <.001), which persisted throughout the study period. The rate of
      completed D-dimer tests per 1000 visits among patients 65 years and older in
      control clinics decreased from 3.14 to 2.11 (95% CI, -1.66 to -0.04; P <.001 for
      interaction). After activation of the alert in control clinics, the rate of
      completed D-dimer tests per 1000 visits among patients 65 years and older
      decreased from 2.11 to 0.81 (95% Cl, -1.79 to -0.80; P <.001). After activation
      of the alert in each clinic group, the ratios of completed venous ultrasonography
      to completed D-dimer tests increased from 1.17 to 4.05 (95% CI, 2.52-3.22) and
      from 2.25 to 7.29 (95% CI, 3.74-6.35) in intervention clinics and control
      clinics, respectively (P <.001 for both). CONCLUSION: An electronic age-specific
      alert targeted to a specific condition reduced D-dimer testing in this elderly
      population of outpatients and demonstrated a persistent effect.

PMID- 21087073
TI  - Dental capitation insurance provider compensation: a fair deal?
AB  - OBJECTIVE: To investigate the fairness of dental capitation insurance provider
      compensation amounts being paid by one of the nation's largest capitation
      insurance companies. STUDY DESIGN: Analysis of insurance company documents.
      METHODS: The article first reports and then analyzes the capitation amounts paid
      by one of the nation's largest capitation plans over the past 13 years as
      retrieved directly from the insurance company documents. The annual rates of
      change in the capitation amounts are then compared with the annual rates of
      change in the mean dental office overhead expenses across the United States, as
      well as with the rates of change in income and expenses of the average US worker.
      RESULTS: The compensation (capitation amount) paid to participating providers
      decreased dramatically every year over the past 13 years, while the mean office
      overhead costs of participating providers increased every year. CONCLUSIONS: Solo
      general dentists with office overhead costs greater than or equal to the national
      mean likely find that the capitation amounts paid by insurance companies are an
      unfair compensation or are incompatible with their income objectives.
      Participation by solo general practitioners in capitation plans with such
      compensation levels would be problematic or unlikely.

PMID- 21087074
TI  - Persistent asthma defined using HEDIS versus survey criteria.
AB  - OBJECTIVES: To describe the relationships between persistent asthma defined by
      administrative versus survey data and their stability over time. STUDY DESIGN:
      Longitudinal survey and retrospective administrative database. METHODS:
      Administrative data were used to identify patients meeting the Healthcare
      Effectiveness Data and Information Set (HEDIS) criteria for persistent asthma in
      year 1 (2006). At the end of year 2 and on 3 occasions during year 3, patients
      were mailed a survey to define persistent asthma based on symptoms and medication
      use in the prior month and exacerbations in the prior 12 months. Administrative
      data were also used to define medical utilization for asthma in year 3. RESULTS:
      Of 13,833 eligible patients, 2895 (20.9%) returned the survey; 2751 of these
      respondents reported physician-diagnosed asthma, of whom 2517 (91.5%) had survey
      defined persistent asthma. Patients having survey-defined persistent asthma
      (68.0%) were more likely to requalify as having HEDIS-defined persistent asthma
      in year 2 than patients not having survey-defined persistent asthma (22.2%).
      However, 81.6% of survey respondents who did not requalify as having HEDIS
      defined persistent asthma in year 2 had survey-defined persistent asthma.
      Patients with survey-defined persistent asthma in year 2 had significantly more
      medical utilization for asthma in year 3 than patients without survey-defined
      persistent asthma. Approximately 82% of the 799 patients completing all 4 surveys
      had persistent asthma on all surveys. CONCLUSIONS: HEDIS-defined persistent
      asthma is generally consistent with survey-defined persistent asthma. Persistent
      asthma usually remains persistent over a 3-year period, indicating that it is a
      stable characteristic of asthma for most patients. The low survey response rate
      suggests that further population-based studies will be necessary to confirm the
      validity and generalizability of our study findings regarding persistent asthma.

PMID- 21087075
TI  - Changing costs and the impact on RSV prophylaxis.
AB  - OBJECTIVE: Acquisition costs of palivizumab have increased in Canada since 2007.
      This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada
      for premature infants born between 32 and 35 weeks' gestational age using updated
      2010 healthcare costs compared to those used in a 2007 decision analytic model.
      METHODS: New costs (CAN$) were acquired from the same Health Canada and Ontario
      Ministry of Health sources that were utilized in the previously published 2007
      model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as
      of August 2010. RESULTS: Incremental cost-effectiveness ratios (ICERs) rose by
      $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a
      range of $801,297 to $820,701 for infants with zero risk factors to a decrease
      from $808 to $192 for infants with four or more risk factors. CONCLUSIONS:
      Palivizumab ICERs remained fairly stable from 2007 to 2010. The original
      recommendation stating that palivizumab is cost effective in infants born between
      32 and 35 weeks' GA with two or more risk factors, or who are at moderate-to-high
      risk based on a risk assessment model, does not change. Analyses founded on
      evolving country-specific variables are needed in order to accurately reassess
      the cost effectiveness of interventions as costs change worldwide. LIMITATIONS:
      There are a limited number of publications reporting mortality in premature
      Canadian infants with RSV as a primary outcome. In addition, conclusions drawn
      from this analysis are country-specific and limited to premature infants dwelling
      in Canada.

PMID- 21087076
TI  - Topoisomerases and site-specific recombinases: similarities in structure and
      mechanism.
AB  - The processes of DNA topoisomerization and site-specific recombination are
      fundamentally similar: DNA cleavage by forming a phospho-protein covalent
      linkage, DNA topological rearrangement, and DNA ligation coupled with protein
      regeneration. Type IB DNA topoisomerases are structurally and mechanistically
      homologous to tyrosine recombinases. Both enzymes nick DNA double helices
      independent of metal ions, form 3'-phosphotyrosine intermediates, and rearrange
      the free 5' ends relative to the uncut strands by swiveling. In contrast, serine
      recombinases generate 5'-phospho-serine intermediates. A 180 degrees  relative
      rotation of the two halves of a 100 kDa terameric serine recombinase and DNA
      complex has been proposed as the mechanism of strand exchange. Here I propose an
      alternative mechanism. Interestingly, the catalytic domain of serine recombinases
      has structural similarity to the TOPRIM domain, conserved among all Type IA and
      Type II topoisomerases and responsible for metal binding and DNA cleavage. TOPRIM
      topoisomerases also cleave DNA to generate 5'-phosphate and 3'-OH groups. Based
      on the existing biochemical data and crystal structures of topoisomerase II and
      serine recombinases bound to pre- and post-cleavage DNA, I suggest a strand
      passage mechanism for DNA recombination by serine recombinases. This mechanism is
      reminiscent of DNA topoisomerization and does not require subunit rotation.

PMID- 21087077
TI  - The potential effect and mechanism of high-mobility group box 1 protein on
      regulatory T cell-mediated immunosuppression.
AB  - To investigate the effect of high-mobility group box 1 (HMGB1) protein on the
      regulatory T cells (Tregs) in vitro and its potential regulating mechanism in
      mice. Splenic CD4(+)CD25(+) Tregs and CD4(+)CD25(-) T cells were isolated. The
      time-dependent and dose-dependent responses between HMGB1 stimulation and
      cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and forkhead/winged helix
      transcription factor p3 (Foxp3) expressions were analyzed. The secretion of
      various cytokines in the cell suspensions and the proliferation of CD4(+)CD25(-)
      T cells were determined. HMGB1 was found to be able to markedly down-regulate the
      expressions of CTLA-4 and Foxp3, especially at 72 h group and in 1,000 ng/mL
      group (both P < 0.01). The expression of Foxp3 mRNA showed a similar tendency as
      Foxp3 protein (P < 0.05 or P < 0.01). The secretion of interleukin (IL)-10 from
      Tregs was decreased when the concentration of HMGB1 was increased. The
      suppressive activity of proliferation of CD4(+)CD25(-) T cells exceeded 90% when
      the ratio of Tregs to CD4(+)CD25(-) T cells was 1:1; meanwhile, the proliferation
      of CD4(+)CD25(-) T cells was enhanced when cultured with HMGB1-stimulated Tregs.
      In the culture of HMGB1-stimulated Tregs, IL-2 and interferon-gamma levels were
      elevated; whereas IL-4 and IL-10 decreased in CD4(+)CD25(-) T cells after the
      increased concentration of HMGB1 in comparison with unstimulated-Treg group.
      HMGB1 stimulation can result in markedly down-regulatory expressions of CTLA-4 as
      well as in Foxp3 expression and secretion of IL-10 from splenic Tregs in mice.
      HMGB1 appears to be involved in modulating cell-mediated immunity by influencing
      proliferation of effector T cells, secretion of IL-2, and cell polarization.

PMID- 21087078
TI  - Genetic and environmental influences on the plasma interleukin-6 concentration in
      patients with a recent myocardial infarction: a case-control study.
AB  - The aim was to study the stimuli responsible for triggering and sustaining the
      plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients
      with a first myocardial infarction before the age of 60 and healthy control
      subjects matched for age and sex. The plasma IL-6 concentration, antibodies
      against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter
      pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single
      nucleotide polymorphism were determined 3 months after the acute event. The
      results showed that patients had higher IL-6 levels than control subjects,
      whereas there were no differences regarding individual or total number (pathogen
      burden) of positive antibody tests against the different pathogens or IL6
      genotype distribution. The plasma IL-6 concentration was associated with the
      number of positive antibody tests in patients and control subjects, whereas
      patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis,
      including traditional coronary heart disease risk factors, antibodies against
      pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6
      concentration. Neither pathogen burden nor IL6 genotype did contribute to the
      variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension,
      case-control status, and age were determinants of the plasma IL-6 concentration.

PMID- 21087079
TI  - Outcome in males with first-episode schizophrenia: 7-year follow-up.
AB  - OBJECTIVES: The early course of schizophrenia is highly variable. We assessed
      outcomes of patients with first-episode schizophrenia at 7-year follow-up.
      METHODS: Consecutively hospitalized male patients were included if they were
      experiencing their first admission for first-episode schizophrenia and were
      reassessed at 1-, 4- and 7-year follow-ups. The psychopathology was evaluated
      using the PANSS, relative decrease of PANSS and remission status based on
      severity of core symptoms. RESULTS: Forty-four of 76 patients were reassessed
      three times. At the end of index hospitalization 73% of patients achieved
      remission; however, after 1, 4 and 7 years, the percentage had dropped to 50, 50
      and 52%, respectively. When compared post-hoc there was no significant difference
      in PANSS and response to treatment between remitters and non-remitters during the
      index hospitalization; however, a significant difference in psychopathology
      emerged first after 1, 4 and 7 years. All patients who had not achieve remission
      after 1 year also failed to achieve remission after 4 and 7 years. CONCLUSIONS:
      Response to treatment during the first psychotic break-through may not be a
      decisive indicator for the outlook of the disease. Our data suggest that when
      deterioration occurs, it does so early after the first episode.

PMID- 21087080
TI  - Calcium-induced apoptosis is delayed by HER1 receptor signalling through the Akt
      and PLCgamma pathways in bladder cancer cells.
AB  - The level of extracellular calcium has been demonstrated to regulate important
      physiological processes like cell growth and apoptosis. We demonstrate that in
      the bladder cancer cell line RT4, an increased extracellular calcium level
      induces apoptosis and that the HER1 receptor functions as a cell survival factor
      and delays apoptosis. After 12 h of calcium treatment (10 mM) apoptosis was
      detected in the RT4 cells. Increased activation of the HER1 receptor was detected
      as soon as 30 min after calcium addition, and the activation decreased again
      after 12 h of incubation, coinciding with the time when apoptosis was detectable.
      Inhibition of HER1 with Gefitinib (5 MUM) or Tyrphostin (AG1478) (20 MUM)
      augmented the calcium-induced apoptosis, and with HER1 inhibition apoptosis was
      detectable after 6 h. Analysis of downstream signalling molecules showed an
      increased activation of Akt, PLCgamma and MAPK in response to calcium treatment.
      The activation of Akt and PLCgamma was abolished by inhibition of HER1 with
      Gefitinib (5 MUM), whereas this had no effect on the activity of MAPK. In
      addition, incubation with inhibitors of Akt and PLCgamma significantly augmented
      calcium-induced apoptosis, whereas this was not seen with MAPK inhibition.
      Finally a significant increase in PKCdelta activity was observed with calcium
      treatment alone and was augmented further with HER1 inhibition. In conclusion we
      show that calcium-induced apoptosis in bladder cancer cells is delayed by HER1
      receptor activation involving the Akt and PLCgamma signalling pathways.

PMID- 21087081
TI  - Dietary sodium reduction in the United States: its importance for women.
AB  - This article highlights sodium intake and risk for cardiovascular disease among
      women in the U.S. population and reviews selected interventions to promote sodium
      reduction conducted by CDC's Division for Heart Disease and Stroke Prevention.

PMID- 21087083
TI  - Characterization of a mutant R11H alphaB-crystallin associated with human
      inherited cataract.
AB  - alphaB-Crystallin plays an important part in cataract development. A novel
      mutation (R11H) was previously detected by our group. In the present study, we
      set out to investigate the possible molecular mechanism by which the R11H
      mutation causes cataract. We found that the mutant alphaB-crystallin exhibits
      folding defects, decreased surface hydrophobicity and enhanced chaperone-like
      activity compared with the wild-type alphaB-crystallin. The mutant protein shows
      nearly the same molecular mass and thermal stability as the wild-type form.
      Transfection studies revealed that the R11H mutant was remarkably similar to the
      wild-type protein in its subcellular distribution, but has an abnormal ability to
      induce cell apoptosis. These results suggest that the changes in hydrophobic
      exposure and the abnormal ability to induce programmed cell death of the mutant
      protein are likely to be responsible for the onset of cataract.

PMID- 21087084
TI  - Advance agreements for mental health care: an examination of process and
      outcomes.
AB  - OBJECTIVE: Despite high demand for anticipatory planning tools in mental health
      there is little Australian research about their implementation. This study
      examines the processes and outcomes of the introduction of structured mental
      health advanced agreements in the Australian Capital Territory. METHOD: Thirty
      three patients with serious mental illness collaborated with a key clinician to
      develop an advanced agreement. Patients and clinicians were provided with
      appropriate education, workbooks and materials. The process and outcomes
      associated with developing and completing an agreement were evaluated with
      patient and clinician interviews and self-report measures. RESULTS: The process
      was strongly accepted by the patients with only 16% discontinuing for reasons
      related to the advanced agreement. Participants strongly endorsed benefits both
      to themselves and to the management of patients' illnesses. Service level
      impediments, particularly clinician acceptance, limited treatment options, and
      the lack of legal force of the agreement were identified. CONCLUSIONS: When
      supported, mental health patients can work collaboratively with clinicians to
      produce anticipatory treatment requests which are beneficial, feasible and
      consistent with good care. Implementation of anticipatory planning in mental
      health will require service-level changes to promote clinician acceptance and to
      embed practices which facilitate these tools as part of routine care.

PMID- 21087085
TI  - Murine aldo-keto reductase family 1 subfamily B: identification of AKR1B8 as an
      ortholog of human AKR1B10.
AB  - Aldo-keto reductase family 1 member B10 (AKR1B10), over-expressed in multiple
      human cancers, might be implicated in cancer development and progression via
      detoxifying cytotoxic carbonyls and regulating fatty acid synthesis. In the
      present study, we investigated the ortholog of AKR1B10 in mice, an ideal modeling
      organism greatly contributing to human disease investigations. In the mouse,
      there are three aldo-keto reductase family 1 subfamily B (AKR1B) members, i.e.,
      AKR1B3, AKR1B7, and AKR1B8. Among them, AKR1B8 has the highest similarity to
      human AKR1B10 in terms of amino acid sequence, computer-modeled structures,
      substrate spectra and specificity, and tissue distribution. More importantly,
      similar to human AKR1B10, mouse AKR1B8 associates with murine acetyl-CoA
      carboxylase-alpha and mediates fatty acid synthesis in colon cancer cells. Taken
      together, our data suggest that murine AKR1B8 is the ortholog of human AKR1B10.

PMID- 21087086
TI  - Increase of SARS-CoV 3CL peptidase activity due to macromolecular crowding
      effects in the milieu composition.
AB  - The 3C-like peptidase of the severe acute respiratory syndrome virus (SARS-CoV)
      is strictly required for viral replication, thus being a potential target for the
      development of antiviral agents. In contrast to monomeric picornavirus 3C
      peptidases, SARS-CoV 3CLpro exists in equilibrium between the monomer and dimer
      forms in solution, and only the dimer is proteolytically active in dilute buffer
      solutions. In this study, the increase of SARS-CoV 3CLpro peptidase activity in
      presence of kosmotropic salts and crowding agents is described. The activation
      followed the Hofmeister series of anions, with two orders of magnitude
      enhancement in the presence of Na2SO4, whereas the crowding agents polyethylene
      glycol and bovine serum albumin increased the hydrolytic rate up to 3 times.
      Kinetic determinations of the monomer dimer dissociation constant (K(d))
      indicated that activation was a result of a more active dimer, without
      significant changes in K(d) values. The activation was found to be independent of
      substrate length and was derived from both k(cat) increase and K(m) decrease. The
      viral peptidase activation described here could be related to the crowded
      intracellular environment and indicates a further fine-tuning mechanism for
      biological control, particularly in the microenvironment of the vesicles that are
      induced in host cells during positive strand RNA virus infection.

PMID- 21087087
TI  - Obsessive-compulsive symptoms in first episode psychosis and in subjects at ultra
      high risk for developing psychosis; onset and relationship to psychotic symptoms.
AB  - OBJECTIVE: To determine the prevalence of obsessive-compulsive symptoms and
      obsessive-compulsive disorder in patients with schizophrenia or related disorders
      or subjects at ultra high risk for development of psychosis. Secondly, to
      determine the time of occurrence of obsessive-compulsive symptoms related to the
      onset of first psychosis. METHOD: We collected data on all patients who were
      referred consecutively to our specialized clinic for first episode psychosis
      patients and ultra high risk subjects in Amsterdam between 1 July 2006 and 1 July
      2008. Diagnosis of psychotic disorders was established using the Comprehensive
      Assessment of Symptoms and History schedule. Obsessions and compulsions were
      defined in accordance with DSM-III-R criteria and assessed by clinicians. We
      analyzed the onset of obsessive-compulsive symptoms and its relation to the onset
      of first episode psychosis. RESULTS: When a strict definition of obsessive
      compulsive symptoms is used, 9.3% (n = 18) of patients with schizophrenia or a
      related disorder exhibited obsessive-compulsive symptoms and 1.5% also met
      criteria for obsessive-compulsive disorder. The onset of obsessive-compulsive
      symptoms occurred before, concurrent with and after onset of first episode
      psychosis in the following proportion of patients: 7/18, 3/18, 8/18. We found a
      prevalence of 20.7% of obsessive-compulsive symptoms in ultra high risk subjects.
      CONCLUSION: Using a strict definition of obsessive-compulsive symptoms, we found
      relatively low prevalence rates of obsessive-compulsive symptoms and obsessive
      compulsive disorder in patients with schizophrenia or related disorders; the
      rates are even lower than known rates of obsessive-compulsive symptoms and
      obsessive-compulsive disorder in the general population. Obsessive-compulsive
      symptoms rates in ultra high risk subjects are comparable to those in the general
      population. Further investigation of the predictive validity of obsessive
      compulsive symptoms in ultra high risk subjects for developing psychosis is
      needed. Obsessive-compulsive symptoms either develop prior, during or after the
      onset of first episode psychosis.

PMID- 21087088
TI  - Secretion of hepatoma-derived growth factor is regulated by N-terminal
      processing.
AB  - Hepatoma-derived growth factor (HDGF) was first purified as a growth factor
      secreted by hepatoma cells. It promotes angiogenesis and has been related to
      tumorigenesis. To date, little is known about the molecular mechanisms of HDGF
      functions and especially its routes or regulation of secretion. Here we show that
      secretion of HDGF requires the N-terminal 10 amino acids and that this peptide
      can mediate secretion of other proteins, such as enhanced green fluorescent
      protein, if fused to their N-terminus. Our results further demonstrate that
      cysteine residues at positions 12 and 108 are linked via an intramolecular
      disulfide bridge. Surprisingly, phosphorylation of serine 165 in the C-terminal
      part of HDGF plays a critical role in the secretion process. If this serine is
      replaced by alanine, the N-terminus is truncated, the intramolecular disulfide
      bridge is not formed and the protein is not secreted. In summary, these
      observations provide a model of how phosphorylation, a disulfide bridge and
      proteolytic cleavage are involved in HDGF secretion.

PMID- 21087089
TI  - Characterization of plant miRNAs and small RNAs derived from potato spindle tuber
      viroid (PSTVd) in infected tomato.
AB  - To defend against invading pathogens, plants possess RNA silencing mechanisms
      involving small RNAs (miRNAs, siRNAs). Also viroids - plant infectious, non
      coding, unencapsidated RNA - cause the production of viroid-specific small RNAs
      (vsRNA), but viroids do escape the cytoplasmic silencing mechanism. Viroids with
      minor sequence variations can produce different symptoms in infected plants,
      suggesting an involvement of vsRNAs in symptom production. We analyzed by deep
      sequencing the spectrum of vsRNAs induced by the PSTVd strain AS1, which causes
      strong symptoms such as dwarfing and necrosis upon infection of tomato plants cv
      Rutgers. Indeed, vsRNAs found with highest frequency mapped to the pathogenicity
      modulating domain of PSTVd, supporting an involvement of vsRNAs in symptom
      production. Furthermore, in PSTVd AS1-infected plants the accumulation of some
      endogenous miRNAs, which are involved in leaf development via regulation of
      transcription factors, is suppressed. The latter finding supports the hypothesis
      that a miRNA-dependent (mis)regulation of transcription factors causes the viroid
      symptoms.

PMID- 21087090
TI  - Physiology and pathophysiology of the RANKL/RANK system.
AB  - The TNF family molecule RANKL and its receptor RANK are key regulators of bone
      remodeling, lymph node formation, and mammary gland development during pregnancy.
      RANKL and RANK are also expressed in the central nervous systems (CNS). However,
      the functional relevance of RANKL/RANK in the brain was entirely unknown.
      Recently, our group reported that the RANKL/RANK signaling pathway has an
      essential role in the central regulation of body temperature via the
      prostaglandin axis. This review discusses novel aspects of the RANKL/RANK system
      as key regulators of fever and female basal body temperature in the CNS.

PMID- 21087091
TI  - Quantitative determination of haptoglobin glycoform variants in psoriasis.
AB  - Haptoglobin is an acute phase glycoprotein, secreted by hepatocytes and other
      types of cells including keratinocytes. Haptoglobin has been suggested to impair
      the immune response, inhibit gelatinases in the extracellular matrix and promote
      angiogenesis, but its role in psoriasis is obscure to date. Changes in
      haptoglobin glycan structure were observed in several diseases. The aim of this
      study was to investigate whether haptoglobin displays glycan variations in
      psoriasis. We found that the pattern of plasma haptoglobin glycoforms, following
      two-dimensional electrophoresis, exhibited significant quantitative differences
      in spot intensities between patients and controls. Quantitative and qualitative
      differences in glycan mass, between patients and controls, were found by mass
      spectrometry of glycopeptides from tryptic digests of protein isolated from both
      patients and controls. The number of distinct fucosylated glycoforms of peptides
      NLFLNHSENATAK and MVSHHNLTTGATLINEQWLLTTAK was higher in patients than in
      controls, but no fucosylated glycan was detected on peptide VVLHPNYSQ-VDIGLIK in
      either case. The number of peptides with distinct triantennary and tetraantennary
      glycans was higher in patients than in controls. Abundance or structure of
      specific glycans, which are present in haptoglobin from patients and are
      different or missing in normal haptoglobin, might be associated with disease
      activity.

PMID- 21087092
TI  - Oral health: locus of control, health behavior, self-rated oral health and socio
      demographic factors in Istanbul adults.
AB  - OBJECTIVES: To determine oral health control beliefs of Istanbul adults using the
      Multidimensional Oral Health Locus of Control Scale (MOHLCS) after confirming its
      factorial validity and to examine the relationships between these beliefs, self
      rated oral health, oral health behaviors and socio-demographic factors. MATERIAL
      AND METHODS: The MOHLCS was administered to a sample of 1200 subjects aged >=18
      years in Istanbul chosen using a quota-sampling method (response 88%). The
      relationship between the MOHLCS and oral health behaviors, self-rated oral health
      and socio-demographic factors was assessed after confirming the factorial
      validity of the MOHLCS. RESULTS: The MOHLCS demonstrated satisfactory internal
      reliability. Factor analysis results showed a new four-factor solution, namely
      Internal, Dentist, Chance, and Socialization agents. Multivariate analysis showed
      that female gender, younger age, higher socioeconomic status, more frequent daily
      toothbrushing, and regular dental check-ups were associated with higher Internal
      beliefs, while older age, lower educational level, lower socioeconomic status,
      low toothbrushing frequency, and symptom-orientated dental attendance were
      associated with higher Chance beliefs. Being unmarried and low toothbrushing
      frequency were associated with lower Dentist beliefs. Males and older subjects
      had lower Socialization agents beliefs. Internal, Dentist and Chance beliefs were
      significantly associated with self-rated oral health. CONCLUSIONS: Compared with
      the original factor structure, the new factor structure had better goodness of
      fit for this sample. Self-rated oral health, socio-demographic factors, and oral
      health behaviors were significantly associated with oral health control beliefs.
      These beliefs may be useful for planning oral health promotion programs and for
      formulating advice given by oral health professionals about their patients' oral
      health behaviors.

PMID- 21087093
TI  - Psychotic symptoms in refugees diagnosed with PTSD: a series of case reports.
AB  - BACKGROUND: In our clinical work, we treat refugees who have been exposed to
      trauma and who subsequently develop psychotic symptoms. However, the literature
      does not address the relationship between refugees with depression, post
      traumatic stress disorder (PTSD) and psychotic symptoms. Therefore the aim of
      this study is firstly to present a series of cases showing how psychotic symptoms
      may present in refugees diagnosed with PTSD, and secondly to discuss the
      underlying explanations of the involved psychopathology. METHODS: The study is
      based on a presentation of a series of cases. All six cases were selected as they
      fulfilled the following criteria for inclusion: 1) had a refugee background, 2)
      fulfilled the PTSD (F43.1) diagnosis upon treatment start and 3) revealed
      psychotic symptoms during treatment. All six were outpatients at the Psychiatric
      Trauma Clinic for Refugees at Psychiatric Centre Gentofte in Copenhagen during
      2009. RESULTS: Our cases were all characterized by having severe symptoms of
      depression and PTSD. Before treatment start they had a score on the Harvard
      Trauma Questionnaire between 2.9 and 3.8 (cut-off: 2.5), and a score on the
      Hopkins Symptom Checklist-25 between 2.8 and 3.6 (cut-off: 1.8). Additionally,
      all cases suffered from varying degrees of positive psychotic symptoms, including
      auditory hallucinations, olfactory and visual hallucinations, as well as
      persecutory delusions and delusions of reference. CONCLUSION: In conclusion,
      research is needed into the prevalence of psychotic symptoms among refugees with
      depression and PTSD, including the qualitative dimensions of the symptoms in
      order to optimize diagnosis and treatment among this group of psychiatric
      patients.

PMID- 21087094
TI  - Conditional expression of full-length humanized anti-prion protein antibodies in
      Chinese hamster ovary cells.
AB  - Because of their high antigen specificity and metabolic stability, genetically
      engineered human monoclonal antibodies are on the way to becoming one of the most
      promising medical diagnostics and therapeutics. In order to establish an in vitro
      system capable of producing such biosimilar antibodies, we used human constant
      chain sequences to design the novel human antibody expressing vector cassette
      pMAB-ABX. A bidirectional tetracycline (tet)-controllable promotor was used for
      harmonized expression of immunoglobulin type G (IgG) heavy and light chains. As
      an example we used anti-prion protein (anti-PrP) IgGs. Therefore, the variable
      heavy (V(H)) and light chain (V(L)) sequences of anti-PrP antibodies, previously
      generated in our laboratory by DNA immunization of prion protein knock-out mice,
      were isolated from murine hybridoma cell lines and inserted into pMAB-ABX vector.
      After transfection of Chinese hamster ovary (CHO) cells, a number of stable
      antibody producing cell clones were selected. One cell line (pMAB-ABX-13F10/3B5)
      stably expressing the recombinant humanized antibody (rechuAb) 13F10/3B5 was
      selected for detailed characterization by Western blot, immunofluorescence, and
      flow cytometric analyses. The full-length recombinant humanized IgG antibody
      showed a high level of expression in the cytoplasm. In conclusion, the new cell
      system described here is a suitable tool to produce functional intact full-length
      humanized IgG antibodies.

PMID- 21087095
TI  - Comparison of three techniques for generation of tolerogenic dendritic cells:
      siRNA, oligonucleotide antisense, and antibody blocking.
AB  - In recent years, a new view of dendritic cells (DCs) as a main regulator of
      immunity to induce and maintain tolerance has been established. In vitro
      manipulation of their development and maturation is a topic of DC therapeutic
      application, which utilizes their inherent tolerogenicity. In this field, the
      therapeutic potential of antisense, siRNA, and blocking antibody are an
      interesting goal. In the present study, the efficiency of these three methods-
      siRNA, antisense, and blocking antibody--against CD40 molecule and its function
      in DCs and BCL1 cell line are compared. DCs were separated from mouse spleen and
      then cultured in vitro using Lipofectamine 2000 to deliver both silencers; the
      efficacy of transfection was estimated by flow cytometry. mRNA expression and
      protein synthesis were assessed by real time-PCR and flow cytometry,
      respectively. By Annexin V and propidium iodine staining, we could evaluate the
      viability of transfected cells. Knocking down the CD40 gene into separate groups
      of DCs by siRNA, antisense, and blocking antibody treated DCs can cause an
      increase in IL-4, decrease in IL-12, IFN-gamma production, and allostimulation
      activity. Our results indicated that, in comparison to antisense and blocking
      antibody, siRNAs appear to be quantitatively more efficient in CD40
      downregulation and their differences are significant.

PMID- 21087096
TI  - Preparation and characterization of polyclonal antibody against severe acute
      respiratory syndrome-associated coronavirus spike protein.
AB  - A truncated gene (designated S1) encoding the receptor-binding domain (RBD) in
      the spike (S) protein of severe acute respiratory syndrome-associated coronavirus
      (SARS-CoV) was amplified by PCR. The gene was cloned into prokaryotic expression
      vector pGEX-6P-1, resulting in a recombinant plasmid pGEX-SARS-S1. Subsequently,
      pGEX-SARS-S1 was transformed into host cells BL21(DE3)pLysS, and the expression
      of the S1 protein was induced by isopropyl beta-D-thiogalactoside (IPTG).
      Polyclonal antibody against SARS-CoV S1 protein was generated in a rabbit
      immunized with the purified S1 protein. The reactivity of the antibody to the
      SARS-CoV S1 protein was confirmed by Western blot analysis. ELISA indicated that
      the antibody against SARS-CoV S1 protein had no cross reaction with S1 proteins
      of transmissible gastroenteritis virus, a porcine coronavirus, and infectious
      bronchitis virus, an avian coronavirus. The SARS-CoV S1 protein and its antibody
      are valuable reagents for related studies.

PMID- 21087097
TI  - Interleukin-32 gamma specific monoclonal antibody and developing IL-32 specific
      ELISA.
AB  - Cytokines are essential coordinators of defensive immune responses for resolving
      the invasion of pathogens such as bacteria, virus, and fungi. However,
      dysregulated cytokines are the main cause of various autoinflammatory immune
      disorders such as rheumatoid arthritis, inflammatory bowel disease, and
      psoriasis. Interleukin-32 (IL-32) is a recently described cytokine and
      characterized as a proinflammatory cytokine. IL-32 stimulates monocytes and
      macrophages to induce important proinflammatory cytokines (IL-1beta, IL-6, and
      TNFalpha) and chemokines (IL-8 and MIP-2) by activating the NF-kappaB and p38
      mitogen-activated protein (MAP) kinase pathways. The biological activities of IL
      32 are associated with epidemic pathogens, Mycobacterium tuberculosis, influenza
      A virus, and human immunodeficiency virus (HIV). IL-32 is transcribed as six
      alternative splice variants (alpha, beta, gamma, delta, E, and zeta), with IL
      32gamma being the most active isoform. However, it is unclear which isoform is
      related to specific disease activities since there are no high quality antibodies
      available to measure circulating IL-32 in biological samples of patients.
      Therefore, we developed specific anti-human IL-32gamma monoclonal antibodies from
      recombinant human IL-32gamma, which was expressed in Escherichia coli. The IL
      32gamma specific monoclonal antibodies recognized IL-32 in cell culture
      supernatants and serum of IL-32gamma transgenic mice. The newly developed IL
      32gamma monoclonal antibodies will be a useful tool to measure IL-32 level in
      serum samples of various inflammatory diseases. These monoclonal antibodies will
      be helpful in investigating the precise function of IL-32 in immune responses and
      in autoinflammatory diseases.

PMID- 21087098
TI  - Development of isoform-specific monoclonal antibodies against human IL-18 binding
      protein.
AB  - Interleukin-18 binding protein (IL-18BP) is a soluble antagonist of IL-18
      originally discovered while attempting to isolate a soluble receptor by using IL
      18-ligand affinity column. IL-18BP has four isoforms (a, b, c, and d) in humans
      and two isoforms (c and d) in mice. The human isoforms IL-18BPa and IL-18BPc
      neutralize IL-18 activity sufficiently at an equimolar ratio; however IL-18BPb
      and IL-18BPd isoforms lack a complete Ig domain at C-terminus and lose the
      ability to neutralize IL-18 activity. Mouse IL-18BPc and IL-18BPd isoforms,
      possessing a similar complete Ig domain, also neutralize the biological activity
      of mouse IL-18 at an equimolar ratio. Here we expressed recombinant proteins of
      the active human IL-18BP isoforms and developed monoclonal antibodies (MAbs)
      against human IL-18BP a and c isoforms. We obtained two MAbs (78-4 and 38-3) of
      human IL-18BPa and two MAbs (18-7 and 29-6) of human IL-18BPc. The MAb clones 18
      7 and 29-6 specifically recognized recombinant IL-18BPc in Western blot analyses
      and ELISA, whereas the MAb clone 78-4 recognized both isoforms in Western blot
      analyses, but only human IL-18BPa isoform in ELISA. We developed a sandwich ELISA
      by using the monoclonal antibody specific to human IL-18BPa isoform. The isoform
      specific anti-human IL-18BP MAb may be a useful tool in categorizing a distinct
      group of patients from various autoimmune diseases related to IL-18BP.

PMID- 21087099
TI  - Antibody against biologically active p40 subunit of porcine interleukin-12
      expressed in Escherichia coli.
AB  - A truncated p40 subunit of porcine interleukin-12 (pIL-12) gene without the N
      terminal signal peptide sequence was amplified by PCR and cloned into prokaryotic
      expression vector pGEX-6P-1. The resulting recombinant plasmid pGEX-IL12-40 was
      transformed into host cells BL21(DE3)pLysS, and the expression of the p40 subunit
      was induced using isopropyl beta-D-thiogalactoside (IPTG). An anti-p40 polyclonal
      antibody was generated by immunizing a rabbit with the purified protein.
      Immunoreactivities of the p40 protein and the antibody were confirmed by
      immunoblotting. At the same time, a recombinant plasmid expressing the entire pIL
      12 consisting of p35 and p40 genes was constructed by splicing by overlap
      extension (SOE)-PCR and transiently transfected into BHK-21 cells. Expression of
      p40 subunit on the surface of the transfected cells was identified using the anti
      p40 antibody. The p40 protein and the specific antibody are biologically active
      and can be used as detecting reagents.

PMID- 21087100
TI  - Expression, antibody generation, and biological analysis of chicken interleukin
      18.
AB  - The gene encoding mature chicken interleukin-18 (ChIL-18) was cloned into
      prokaryotic expression vector pET-30a(+), resulting in a recombinant plasmid pET
      30a-ChIL-18. After pET-30a-ChIL-18 was transformed into Escherichia coli Rosseta,
      the expression of ChIL-18 induced by 1 mM IPTG at 37 degrees C was analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The expressed fusion
      protein of 26 kDa was purified with a Ni-NTA affinity column and used to generate
      a hyperimmune antiserum in a rabbit. The specificity and titer of anti-ChIL-18
      serum were analyzed by the enzyme-linked immunosorbent assay. Western blot and
      immunofluorescence assays indicated that the anti-ChIL-18 antibody specifically
      reacted with the ChIL-18 expressed from E. coli or ChIL-18-transfected eukaryotic
      cells. Moreover, the renatured ChIL-18 stimulated the production of nitric oxide
      (NO) from macrophages via eliciting the secreting of IFN-gamma from lymphocytes.

PMID- 21087102
TI  - What do the next 100 years hold for pneumococcal vaccination?

PMID- 21087101
TI  - Expression, purification, and characterization of anti-plumbagin single-chain
      variable fragment antibody in Sf9 insect cell.
AB  - Plumbagin (PL; 5-hydroxy-2-methyl-1, 4-naphthoquinone) is an important secondary
      metabolite, mainly produced in the Plumbago zeylanica L. (Plumbaginaceae). A
      single-chain variable fragment (scFv) antibody, fusion of the variable regions of
      the heavy chain and light chain of immunoglobulin against PL (PL-scFv) was
      expressed by Bac-to-Bac Baculovirus Expression System using Spodoptera frugiperda
      (Sf9) insect cells and characterized to investigate potential use of PL-scFv as a
      tool for plant immunomodulation. Functional PL-scFv expressed in the Sf9 insect
      cells were purified using cation exchange chromatography followed by immobilized
      metal ion affinity chromatography (IMAC). The yields of the purified PL-scFv in
      the culture supernatant and Sf9 insect cells were 2.0 mg and 5.2 mg per 1 liter
      of Sf9 culture medium, respectively. Recombinant purified PL-scFv was then
      characterized by the indirect competitive enzyme-linked immunosorbent assay
      (ELISA). The cross-reactivity and sensitivity of PL-scFv expressed in Sf9 insect
      cells were compared with PL-scFv expressed in Escherichia coli and its parental
      anti-plumbagin monoclonal antibody (MAb 3A3) secreted from hybridoma cells.
      Intriguingly, the specificity of the PL-scFv expressed in Sf9 insect cells was
      found to be different from that expressed in E. coli and parental MAb 3A3,
      although the detectable level (0.2-25 MUg/mL) was the same in ELISA using each
      antibody. Even more interestingly, the characteristics of PL-scFv, which have
      wide cross-reactivity against 1,4-napththoquinone, suggest its potential use as a
      tool for plant immunomodulation not only for breeding Plumbaginacea family
      containing PL but also for breeding other medicinal plants containing bioactive
      naphthoquinones.

PMID- 21087103
TI  - Nanomedicine and immunotherapy.

PMID- 21087105
TI  - Liposomes modified by carbohydrate ligands can target B cells for the treatment
      of B-cell lymphomas.
AB  - Evaluation of: Chen WC, Completo GC, Sigal DS, Crocker PR, Saven A, Paulson JC.
      In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood 115(23),
      4778-4786 (2010). A strategy has been developed to deliver selectively
      chemotherapeutic drugs to B cells by employing doxorubicin-loaded liposomes
      modified by a ligand for the B-cell-specific cell-surface protein CD22, also
      known as Siglec-2. The liposomes bound in a rapid and saturable manner to the
      human Burkitt lymphoma Daudi B-cell line and exhibited significantly higher
      cytotoxicity in vitro and in vivo compared with similar untargeted liposomes. The
      CD22-targeted liposome bound to B cells isolated from lymphoma patients and
      although binding was proportional to CD22 expression on the cell surface, low
      levels of expression on chronic lymphocytic leukemia cells were sufficient to
      effect cell neutralization. The glycan-based strategy for delivery of
      chemotherapeutic agents may provide a new strategy for the treatment of B-cell
      lymphomas.

PMID- 21087106
TI  - Carbohydrate-based vaccines: challenges and opportunities.
AB  - Advances in the synthesis of oligo- or polysaccharides and new technologies
      developed in glycobiology studies have opened a new avenue in carbohydrate
      vaccine design. In principle, various types of cell-surface epitopes,
      characteristic of the invading organism or related to aberrant growth of cells,
      can be applied to develop vaccines. Numerous promising carbohydrate-based vaccine
      candidates have been prepared in recent years. This article, primarily for
      general readers, briefly presents the recent advances involving carbohydrate
      based vaccines, including antibacterial, antiparasite, anticancer and antivirus
      vaccines.

PMID- 21087107
TI  - Use of attenuated paramyxoviruses for cancer therapy.
AB  - Paramyxoviruses, measles virus (MV), mumps virus (MuV) and Newcastle disease
      virus (NDV), are well known for causing measles and mumps in humans and Newcastle
      disease in birds. These viruses have been tamed (attenuated) and successfully
      used as vaccines to immunize their hosts. Remarkably, pathogenic MuV and vaccine
      strains of MuV, MV and NDV efficiently infect and kill cancer cells and are
      consequently being investigated as novel cancer therapies (oncolytic
      virotherapy). Phase I/II clinical trials have shown promise but treatment
      efficacy needs to be enhanced. Technologies being developed to increase treatment
      efficacy include: virotherapy in combination with immunosuppressive drugs
      (cyclophosphamide); retargeting of viruses to specific tumor types or tumor
      vasculature; using infected cell carriers to protect and deliver the virus to
      tumors; and genetic manipulation of the virus to increase viral spread and/or
      express transgenes during viral replication. Transgenes have enabled noninvasive
      imaging or tracking of viral gene expression and enhancement of tumor
      destruction.

PMID- 21087109
TI  - Respective roles of TLR, RIG-I and NLRP3 in influenza virus infection and
      immunity: impact on vaccine design.
AB  - Influenza A virus is the etiological agent of a highly contagious acute
      respiratory disease that causes epidemics and considerable mortality annually. It
      has become increasingly evident that influenza viral infection is recognized by
      at least three classes of pattern-recognition receptors, including TLR-7, the
      retinoic acid inducible gene-I and nucleotide-binding domain and leucine-rich
      repeat-containing protein 3, a member of the Nod-like receptor family. This
      article highlights the roles of different types of innate immune receptors in
      influenza virus immunity versus immunopathology.

PMID- 21087108
TI  - Update on the current status of cytomegalovirus vaccines.
AB  - Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most
      commonly recognized cause of congenital viral infection in developed countries.
      On the basis of the economic costs saved and the improvement in quality of life
      that could potentially be conferred by a successful vaccine for prevention of
      congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine
      development as a major public health priority. An effective vaccine could
      potentially also be beneficial in preventing or ameliorating HCMV disease in
      immunocompromised individuals. Although there are no licensed HCMV vaccines
      currently available, enormous progress has been made in the last decade, as
      evidenced by the recently reported results of a Phase II trial of a glycoprotein
      B vaccine for the prevention of HCMV infection in seronegative women of
      childbearing age. HCMV vaccines currently in clinical trials include:
      glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA
      vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also
      being examined in preclinical systems and animal models of infection. These
      include: recombinant vesicular stomatitis virus vaccines; recombinant modified
      vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and
      recombinant live-attenuated virus vaccines generated by mutagenesis of cloned
      rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia
      coli. In this article, we provide an overview of the current state of clinical
      trials and preclinical development of vaccines against HCMV, with an emphasis on
      studies that have been conducted in the past 5 years. We also summarize a number
      of recent advances in the study of the biology of HCMV, particularly with respect
      to epithelial and endothelial cell entry of the virus, which have implications
      for future vaccine design.

PMID- 21087110
TI  - Cross-protective immunity to influenza A viruses.
AB  - Antigenic changes in influenza virus occur gradually, owing to mutations
      (antigenic drift), and abruptly, owing to reassortment among subtypes (antigenic
      shift). Availability of strain-matched vaccines often lags behind these changes,
      resulting in a shortfall in public health. In animal models, cross-protection by
      vaccines based on conserved antigens does not completely prevent infection, but
      greatly reduces morbidity, mortality, virus replication and, thus, viral shedding
      and spread. Such immunity is especially effective and long-lasting with mucosal
      administration. Cross-protective immunity in humans is controversial, but is
      suggested by some epidemiological findings. 'Universal' vaccines protective
      against all influenza A viruses might substantially reduce severity of infection
      and limit spread of disease during outbreaks. These vaccines could be used 'off
      the shelf' early in an outbreak or pandemic, before strain-matched vaccines are
      available.

PMID- 21087111
TI  - Vaccine presentation in the USA: economics of prefilled syringes versus multidose
      vials for influenza vaccination.
AB  - In the USA, influenza vaccines are available as parenteral injections or as an
      intranasal preparation. Injectable influenza vaccines are available in either
      multidose vial (MDV), single-dose vial or prefilled syringe (PFS) presentations.
      PFSs have gained market share in the USA but have not yet reached the levels of
      uptake currently seen in Western Europe. Here, we review the topic of vaccine
      presentation in the USA, with a special focus on influenza vaccines. Second, we
      present the results of a time-motion study that measured administration costs of
      influenza vaccination comparing MDVs versus PFSs during the 2009/2010 influenza
      campaign. Vaccinating with MDVs took an average 37.3 s longer than PFSs. The cost
      of administering 1000 immunizations in 2009 using MDVs were US$8596 versus
      US$8920.21 using PFSs. In a pandemic situation where 300 million Americans would
      require vaccination, PFSs would save 3.12 million h in healthcare worker time,
      worth US$111.1 million. The higher acquisition costs of PFS vaccines compared
      with MDVs are offset by lower administrative costs and increased safety.

PMID- 21087114
TI  - Presence and ex vivo formation of acridone in blood of patients routinely treated
      with carbamazepine: exploration of the 9-acridinecarboxaldehyde pathway.
AB  - Carbamazepine (CBZ) is a useful anticonvulsive drug associated with rare severe
      adverse drug reactions. The physio-pathological mechanisms of these reactions are
      unknown although evidence of immunological activation has been reported. The
      ability of 9-acridinecarboxaldehyde, a CBZ metabolite, to interact with leukocyte
      constituents was demonstrated, and catabolism of this compound into acridine (AI)
      and acridone (AO) was observed in vitro. In this study, we have assessed ex vivo
      the role of the extra-hepatic 9-acridinecarboxaldehyde pathway in the metabolism
      of CBZ. First, we verified the presence of the terminal metabolites AI and AO in
      CBZ-treated patients. Then, we tested ex vivo the transformation of CBZ, epoxy
      CBZ, iminostilbene, and AI into AO in the blood of these patients. We observed no
      direct formation of hydroxylated CBZ metabolites in isolated blood, and CBZ did
      not react with blood cells. Conversely, we detected a dose-dependent
      transformation of epoxy CBZ, iminostilbene, and AI into AO with individual
      variations from patient to patient. AO might thus be considered as a metabolite
      of 9-acridinecarboxaldehyde that does not react with cells (detoxicant pathway)
      as well as a marker of the formation of toxic AI derivatives (toxicant pathway).

PMID- 21087113
TI  - Disturbance in cerebral spinal fluid sphingolipid content is associated with
      memory impairment in subjects infected with the human immunodeficiency virus.
AB  - Despite widespread use of antiretroviral therapies to control replication of the
      human immunodeficiency virus (HIV), dysfunctions of cognition that are
      collectively termed HIV-associated neurocognitive disorders (HAND) still occur in
      approximately 50% of those infected by the virus. Currently there is not a
      biomarker that can identify HIV-infected people who are at risk for the
      development of HAND. Previous studies have identified particular sphingolipid
      species that are dysregulated in HAND, but the neurocognitive correlates of these
      biochemical findings are not currently understood. To address this question, we
      compared cerebrospinal fluid (CSF) levels of sphingomyelin, ceramide, and sterol
      species with performance on standard neurological tests designed to assess the
      function of multiple cognitive and motor domains in HIV-infected subjects. We
      found that sphingomyelin:ceramide ratios for acyl chain lengths of C16:0, C18:0,
      C22:0, and C24:0 were associated with worse performance on several indices of
      memory. The most striking finding was for the acyl chain of C18:0 that
      consistently associated with performance on multiple tests of memory. These
      findings suggest that the sphingomyelin:ceramide ratio for C18:0 may be a
      reasonable surrogate marker for memory dysfunction in HIV-infected subjects.

PMID- 21087115
TI  - Application of cytochrome P450 BM3 mutants as biocatalysts for the profiling of
      estrogen receptor binding metabolites of the mycotoxin zearalenone.
AB  - The estrogenic mycotoxin zearalenone (ZEN) can undergo hepatic reductive
      metabolism to form the estrogenic alpha and beta isomers of zearalenol. ZEN also
      undergoes cytochrome P450 monooxygenase (P450)-mediated oxidative metabolism to
      form monohydroxylated products, but until now nothing is known about the
      estrogenic potency of these metabolites. This study aimed at investigating the
      metabolism of ZEN by different P450 isoforms and to determine the estrogen
      receptor alpha (ERalpha) affinities of the in vitro P450-generated ZEN
      metabolites in an online high-resolution screening (HRS) setup. Human liver
      microsomes (HLM), recombinant P450s, and mutants of the bacterial P450 BM3 were
      used to investigate the oxidative metabolism of ZEN. It was shown that mutants of
      the bacterial P450 BM3 could be used to produce the human relevant 13- and 15-OH
      ZEN catechol metabolites at such levels that their ERalpha affinity could be
      determined in an HRS setup, which was not possible with HLM. It was demonstrated
      that P450-mediated hydroxylation at the 13 and 15 positions of ZEN resulted in a
      loss of ERalpha affinity. The approach presented here can be used for the
      elucidation of the metabolism of other endocrine disrupting compounds and
      xenobiotics to get clear pictures of the total effects of these compounds and
      their metabolites.

PMID- 21087117
TI  - In vitro metabolism study of 2-isopropyl-9H-thioxanthen-9-one (2-ITX) in rat and
      human: evidence for the formation of an epoxide metabolite.
AB  - 1. 2-Isopropyl-9H-thioxanthen-9-one (2-ITX) is one of the most extensively used
      photoinitiators in inks found in paper and/or packaging materials for foodstuffs.
      Recently, traces of 2-ITX as a contaminant were discovered in baby milk and other
      foodstuffs at a level sufficient to pose a risk to human health. However, little
      is known about the toxicological profile of 2-ITX. 2. The high lipophilicity of
      this substance would suggest that it could be a good substrate for hepatic
      metabolizing enzymes and that these metabolites could have a role in the
      toxicological properties of 2-ITX. 3. The metabolism of 2-ITX, using both rat and
      human subcellular preparations, was studied and has resulted in the formation of
      eight polar metabolites (M1-M8) as revealed in the liquid
      chromatograpy/ultraviolet (LC/UV) and liquid chromatograpy/mass spectrometry
      (LC/MS) analyses. Their structures highlight a marked regioselectivity in the
      metabolism of 2-ITX; it is directed mainly toward the isopropyl moiety and the
      sulfur atom. 4. The unsaturated metabolite 6 causes the formation of a reactive
      epoxide metabolite 7. This finding was supported by identification in microsomal
      incubations of 1,2-diol metabolite 8 arising from the epoxide by hydrolysis and
      it was validated by incubating in the same conditions the synthetic epoxide 7:
      the formation of metabolite 8 was again observed. 5. On the basis of these data,
      we propose that the metabolite 6 could be included in toxicological studies of 2
      ITX.

PMID- 21087116
TI  - Metabolism of alpha-thujone in human hepatic preparations in vitro.
AB  - This study aims to characterize the metabolism of alpha-thujone in human liver
      preparations in vitro and to identify the role of cytochrome P450 (CYP) and
      possibly other enzymes catalyzing alpha-thujone biotransformations. With a liquid
      chromatography-mass spectrometry (LC-MS) method developed for measuring alpha
      thujone and four potential metabolites, it was demonstrated that human liver
      microsomes produced two major (7- and 4-hydroxy-thujone) and two minor (2-hydroxy
      thujone and carvacrol) metabolites. Glutathione and cysteine conjugates were
      detected in human liver homogenates, but not quantified. No glucuronide or
      sulphate conjugates were detected. Major hydroxylations accounted for more than
      90% of the primary microsomal metabolism of alpha-thujone. Screening of alpha
      thujone metabolism with CYP recombinant enzymes indicated that CYP2A6 was
      principally responsible for the major 7- and 4-hydroxylation reactions, although
      CYP3A4 and CYP2B6 participated to a lesser extent and CYP3A4 and CYP2B6 catalyzed
      minor 2-hydroxylation. Based on the intrinsic efficiencies of different
      recombinant CYP enzymes and average abundances of these enzymes in human liver
      microsomes, CYP2A6 was calculated to be the most active enzyme in human liver
      microsomes, responsible for 70-80% of the metabolism on average. Inhibition
      screening indicated that alpha-thujone inhibited both CYP2A6 and CYP2B6, with 50%
      inhibitory concentration values of 15.4 and 17.5 uM, respectively.

PMID- 21087118
TI  - Gender differences in quality of schoolwork task performance among typically
      developing students and students at risk of or with mild disabilities.
AB  - AIM: As no studies have examined for gender differences in quality of schoolwork
      task performance, the purpose of this study was to examine whether there is a
      gender difference in quality of schoolwork task performance among students at
      risk of or with mild disabilities, and to compare any identified differences to
      those that might exist among their typically developing peers. METHODS: The
      participants were 2510 students (typically developing = 412 girls, 422 boys; at
      risk = 147 girls, 379 boys; mild = 242 girls, 901 boys), 4-10 years of age.
      Schoolwork task performance was measured using the School Version of the
      Assessment of Motor and Process Skills (School AMPS). RESULTS: Regression
      analyses revealed no significant gender or age-by-gender interaction effects for
      any of the three groups (typically developing, at risk, mild). INTERPRETATION:
      The results, focused on occupational performance, complement prior research that
      has focused on examining for gender differences in behaviour, academic
      achievement, and coordination among students with mild disabilities. These
      results also suggest that current School AMPS normative values, based on combined
      gender means, are valid.

PMID- 21087119
TI  - Cut-off levels and diagnostic accuracy of infliximab trough levels and anti
      infliximab antibodies in Crohn's disease.
AB  - INTRODUCTION: Reasons for infliximab failure in Crohn's disease and ulcerative
      colitis are debated. Serum levels of infliximab and anti-infliximab antibodies
      have been associated with loss of response. We aimed at determining cut-off
      levels for infliximab and anti-infliximab antibody concentrations associated with
      clinical response to infliximab maintenance therapy. METHODS: Patients with
      inflammatory bowel disease (n = 106) were retrospectively classified as having
      maintained response or loss of response to infliximab maintenance therapy. Trough
      concentrations were measured by fluid-phase radioimmunoassays. RESULTS:
      Infliximab levels were significantly lower, and anti-infliximab antibody levels
      significantly higher, in Crohn's disease patients with loss of response (median
      infliximab 0 MUg/ml, median anti-infliximab antibodies 35 U/ml) compared to
      patients with maintained response (median infliximab 2.8 MUg/ml, median anti
      infliximab antibodies 0 U/ml; p < 0.0001). Receiver operating characteristic
      (ROC) analysis identified optimal cut-off values: infliximab <0.5 MUg/ml, which
      was associated with loss of response with sensitivity 86% [64-97] and specificity
      85% [72-94]; and anti-infliximab antibodies >=10 U/ml yielding a sensitivity of
      81% [61-93] and specificity 90% [79-96]. Combined measurements of infliximab and
      anti-infliximab antibodies using these cut-off values had higher accuracy
      yielding a sensitivity of 81% [57-94] and specificity 94% [82-98]. Similar
      pattern was observed in a smaller cohort of patients with ulcerative colitis.
      CONCLUSIONS: Combined measurements of infliximab and anti-infliximab antibodies
      using cut-off levels provided high accuracy for discriminating between clinical
      response types to infliximab maintenance therapy. Cut-off levels are considered a
      prerequisite to further investigations of clinical usefulness of measurements of
      infliximab and anti-infliximab antibodies in patients failing infliximab therapy.

PMID- 21087120
TI  - Smarcc1 expression: a significant predictor of disease-specific survival in
      patients with clinically localized prostate cancer treated with no intention to
      cure.
AB  - OBJECTIVE: The clinical outcome of prostate cancer (PC) is extremely variable and
      therefore difficult to predict at the early stage of the disease. Since curative
      intended therapies are bound up with the risk of severe adverse events,
      identification of new prognostic markers in PC is essential in individualized
      clinical treatment. The Smarcc1 protein, a part of the intranuclear SWI/SNF
      complex, is up-regulated in PC, and has been suggested to be implicated in tumour
      dedifferentiation, progression and biochemical recurrence. This makes Smarcc1 a
      possible candidate marker for PC survival. MATERIAL AND METHODS:
      Immunohistochemistry was used to measure protein expression levels of Smarcc1in
      on a tissue microarray containing specimens from 100 patients suffering from
      clinically localized PC treated with no intention to cure and followed to death.
      RESULTS: The median age at diagnosis was 75.5 years (55-95 years) and the median
      survival time was 5 years (0.01-15 years). In total, 41 patients (41%) died of
      PC. Statistically, there was no significant association between Smarcc1
      immunostaining (negative/positive) and Gleason score (p = 0.7/0.8) or the
      clinical T stage (p = 0.9). Positive staining for Smarcc1 in patients with
      clinically localized PC correlated with a prolonged disease-free survival as
      opposed to negative staining (p = 0.025). CONCLUSION: In patients with clinically
      localized PC treated without intention of cure, Smarcc1 expression was a
      statistically significant and independent predictor of disease-specific survival.

PMID- 21087121
TI  - Transnational comparison: A retrospective study on e-health in sparsely populated
      areas of the northern periphery.
AB  - Healthcare delivery in the northern periphery of Europe is challenged by
      dispersed populations, geographical complexities (including mountainous terrain
      and inhabited islands), ageing populations, and rising patient expectations. It
      is challenged further by variations in transport networks and information
      communication technology infrastructure. This article provides an overview of e
      health development across the northern periphery areas of four northern European
      countries (Finland, Sweden, Norway, and Scotland) by summarizing the outcomes of
      a mixed methods e-health mapping exercise and subsequently identifying service
      needs and gaps. A total of 148 applications, with a range of applied e-health
      solutions, were identified and the findings have promoted the sharing and
      transfer of e-health innovation across the four countries. The supporting
      telecommunications infrastructure and development of innovative telemedicine
      appear slower in sparsely populated areas of Scotland in comparison to its
      northern peripheral counterparts. All four countries have, however, demonstrated
      a clear commitment to the development of e-health within their remote and rural
      regions.

PMID- 21087122
TI  - Two-way text messaging for health behavior change among human immunodeficiency
      virus-positive individuals.
AB  - BACKGROUND: text-messaging systems have been used to promote a range of health
      behaviors, including medication adherence among human immunodeficiency virus
      positive individuals. However, little is currently known about the specific
      characteristics of messaging systems that promote user engagement. OBJECTIVE:
      using data from a randomized controlled trial involving a pager-based text
      messaging system, this study sought to examine the overall usability of the
      system, user evaluation of the system, demographic and psychosocial correlates of
      usability, and its performance as an adherence assessment tool. MATERIALS AND
      METHODS: the messaging system consisted of an alphanumeric pager capable of
      sending and receiving individualized text messages and the software necessary to
      program and track communication. The system was evaluated using behavioral
      outcomes (pager message response rate), self-report survey responses, focus group
      discussions, and data from electronic medication monitoring pill bottles.
      RESULTS: Although the majority of participants reported that the system was
      effective in reminding them to take medication doses, the overall response rate
      to system messages was relatively low (42.8%) and dropped significantly over the
      course of the 3-month intervention period. In addition, user engagement did not
      differ significantly by most demographic and psychosocial variables. CONCLUSIONS:
      the pager-based text messaging system was received well by participants and
      appears to be applicable to a broad population; however, the system did not
      actively engage all participants over the course of the trial. Future research
      should determine whether systems customized to personal preference in
      notification style, frequency, and user device can increase use and provide
      further assistance to achieve optimal medication adherence.

PMID- 21087123
TI  - Seamless integration of ISO/IEEE11073 personal health devices and ISO/EN13606
      electronic health records into an end-to-end interoperable solution.
AB  - The new paradigm of personal health demands open standards and middleware
      components that permit transparent integration and end-to-end interoperability
      from new personal health devices to healthcare information system. The use of
      standards seems to be the internationally accepted way to face this challenge. In
      this article, the implementation of an end-to-end standard-based personal health
      solution is presented. It integrates the ISO/IEEE11073 standard for the
      interoperability of personal health devices in the patient environment and the
      ISO/EN13606 standard for the interoperable exchange of electronic healthcare
      records and proposes a new approach for the end-to-end ISO/IEEE11073-ISO/EN13606
      communication. The design strictly fulfills all the technical requirements of the
      most recent versions of both standards. An entire prototype has been designed,
      developed, and tested as a proof-of-concept of a personal health solution.

PMID- 21087124
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) carriage in 10 nursing homes
      in Orange County, California.

PMID- 21087125
TI  - Clustered randomized controlled trial of a hand hygiene intervention involving
      pocket-sized containers of alcohol-based hand rub for the control of infections
      in long-term care facilities.
AB  - OBJECTIVE: To investigate the effectiveness of a multifaceted hand hygiene
      program involving the use of pocket-sized containers of antiseptic gel in long
      term care facilities (LTCFs) with elderly residents. METHODS: In this clustered
      randomized controlled trial, Hong Kong LTCFs for elderly persons were recruited
      via snowball sampling. Staff hand hygiene adherence was directly observed, and
      residents' infections necessitating hospitalization were recorded. After a 3
      month preintervention period, LTCFs were randomized to receive pocket-sized
      containers of alcohol-based gel, reminder materials, and education for all HCWs
      (treatment group) or to receive basic life support education and workshops for
      all healthcare workers (HCWs) (control group). A 2-week intervention period
      (April 1-15, 2007) was followed by 7 months of postintervention observations.
      RESULTS: In the 3 treatment LTCFs, adherence to hand rubbing increased from 5
      (1.5%) of 333 to 233 (15.9%) of 1,465 hand hygiene opportunities (P = .001)and
      total hand hygiene adherence increased from 86 (25.8%) of 333 to 488 (33.3%) of
      1,465 opportunities (P = .01)after intervention; the 3 control LTCFs showed no
      significant change. In the treatment group, the incidence of serious infections
      decreased from 31 cases in 21,862 resident-days (1.42 cases per 1,000 resident
      days) to 33 cases in 50,441 resident-days (0.65 cases per 1,000 resident-days) (P
      = .002), whereas in the control group, it increased from 16 cases in 32,726
      resident-days (0.49 cases per 1,000 resident-days) to 85 cases in 81,177 resident
      days (1.05 cases per 1,000 resident-days) (P = .004]). In the treatment group,
      the incidence of pneumonia decreased from 0.91 to 0.28 cases per 1,000 resident
      days (P = .001) and the death rate due to infection decreased from 0.37 to 0.10
      deaths per 1,000 resident-days (P = .01); the control group revealed no
      significant change. CONCLUSIONS: A hand hygiene program involving the use of
      pocket-sized containers of antiseptic gel and education could effectively
      increase adherence to hand rubbing and reduce the incidence of serious infections
      in LTCFs with elderly residents.

PMID- 21087126
TI  - Role of patient awareness in prevention of peripheral vascular catheter-related
      bloodstream infection.

PMID- 21087127
TI  - Hospital capacity during an influenza pandemic-Buenos Aires, Argentina, 2009.
AB  - At a major referral hospital in the Southern Hemisphere, the 2009 influenza A
      (H1N1) pandemic brought increased critical care demand and more unscheduled
      nursing absences. Because of careful preparedness planning, including rapid
      expansion and redistribution of the numbers of available beds and staff, hospital
      surge capacity was not exceeded.

PMID- 21087128
TI  - Oncologic outcome of robot-assisted laparoscopic prostatectomy in the high-risk
      setting.
AB  - BACKGROUND AND PURPOSE: Previous studies have demonstrated the feasibility of
      open radical prostatectomy in the high-risk setting. Management of high-risk
      disease with robot-assisted laparoscopic radical prostatectomy (RALP) is
      controversial. We examined biochemical recurrence in a selected cohort of high
      risk patients who were undergoing RALP. PATIENTS AND METHODS: Men with high-risk
      prostate cancer who underwent bilateral nerve-sparing, nonsalvage RALP by a
      single surgeon without adjuvant or neoadjuvant therapy of any kind were
      identified. High risk was defined by preoperative prostate-specific antigen (PSA)
      level >10 ng/dL, Gleason score >=8 on final pathologic evaluation, or stage
      >=pT(3). Postoperative PSA value >=0.2 ng/dL defined biochemical recurrence.
      RESULTS: A total of 73 men were identified. There was no significant difference
      in surgical margin positivity (38% overall) or prostate size between recurrence
      and nonrecurrence cohorts. Biochemical failure was significantly associated with
      higher pathologic Gleason score (P = 0.0085) but not pathologic stage (P = 0.22)
      or preoperative PSA level (P = 0.18). With follow-up to 85 months (mean 31.8
      mos), biochemical recurrence-free survival was 77% with mean time to recurrence
      of 7.7 months. Recurrence occurred significantly earlier than later (P < 0.001).
      CONCLUSIONS: Reasonable short- to intermediate-term biochemical outcomes can be
      achieved in a recurrence-prone group of high-risk men who are undergoing RALP.
      RALP is feasible in a selected cohort of high-risk men who are undergoing
      aggressive local therapy.

PMID- 21087140
TI  - Increasing CTL targeting of conserved sequences during early HIV-1 infection is
      correlated to decreasing viremia.
AB  - Early HIV-1 infection is marked by rapid evolution of both CD8(+) T lymphocyte
      (CTL) epitope targeting and viral sequences, while chronic infection demonstrates
      relative stability of these parameters. To examine the interactions of changing
      CTL targeting and viremia in early infection, we assessed CTL targeting and
      viremia levels in persons during early HIV-1 infection (estimated 15-271 days
      post-infection) who were placed on effective antiretroviral therapy. Pre-therapy,
      CTL targeting of viral proteins varied between persons depending on time after
      infection. Across individuals, increasing time after infection was associated
      with increasing Gag and Pol targeting, suggesting increasing targeting of
      conserved sequences. The intensity of Gag targeting correlated to lower viremia
      levels, while Env targeting correlated to higher viremia levels during early
      infection. This suggested that shifted targeting towards more conserved sequences
      is involved with the drop of viremia during early infection, consistent with
      prior observations of correlation between Gag targeting and lower viremia during
      chronic infection. After suppressive antiretroviral therapy, CTL targeting was
      generally static, indicating that HIV-1 replication and evolution drives the
      evolution of CTL targeting in early infection. Overall, these data suggest that
      early CTL targeting is directed towards more variable epitopes, causing escape
      and re-targeting until more conserved epitopes are recognized stably in chronic
      infection. Circumventing this natural history by pre-targeting CTL against more
      conserved epitopes with a vaccine could minimize the initial period of viral
      escape and immune damage during acute infection, improving long-term containment
      of HIV-1.

PMID- 21087141
TI  - Unusual cluster of HIV type 1 dual infections in Groningen, The Netherlands.
AB  - In 2007, 14 Dutch men having sex with men (MSM) filed a criminal case against
      three other men, accusing them of administering sedative drugs, sexual abuse, and
      deliberate subcutaneous injections with HIV-1-infected blood. Medical files
      showed that 9 of 17 men presented with an acute HIV-1 infection syndrome during
      2006-2007. Two men were not infected with HIV. Analysis of viral strains in the
      12 MSM and the three alleged donors showed that one donor and six recipients were
      double infected with two distinct HIV-1 subtype B strains, while another five
      recipients and one donor were single infected with either strain. Two men were
      infected with unrelated strains. The finding of multiple double infections with
      very similar HIV-1 strains is without precedent.

PMID- 21087142
TI  - A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child.
AB  - An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe
      headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG)
      test was positive, the histology on the lymph node biopsy revealed budding yeast
      cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal
      fluid. He was treated with intravenous amphotericin B followed by oral
      fluconazole with a good response. Therefore cryptococcal lymphadenitis should be
      considered in the differential diagnosis of children presenting with
      lymphadenopathy and a positive serum CRAG.

PMID- 21087143
TI  - Genetic analysis of the near full-length genome of an HIV type 1 A1/C unique
      recombinant form from northern South Africa.
AB  - Human immunodeficiency virus type 1 (HIV-1) has a high propensity for
      recombination. The epidemic in South Africa is predominantly driven by HIV-1
      subtype C with occasional description of non-subtype C and intersubtype
      recombinant viruses. This report presents the genetic analysis of a unique
      recombinant variant from northern South Africa comprised exclusively of
      subsubtype A1 and subtype C parental viruses. Boot scanning analysis of the near
      full-length genome with the jumping profile Hidden Markov Model revealed a
      genomic arrangement with seven breakpoints of recombination alternating between
      subsubtype A1 and subtype C. Apparently, this is the first report of a unique HIV
      1 A1/C recombinant form from northern South Africa and probably the fifth from
      South Africa. The epidemiologic implication of this variant is unknown.

PMID- 21087144
TI  - The p53/p21(WAF/CIP) pathway mediates oxidative stress and senescence in
      dyskeratosis congenita cells with telomerase insufficiency.
AB  - Telomere attrition is a natural process that occurs due to inadequate telomere
      maintenance. Once at a critically short threshold, telomeres signal growth
      arrest, leading to senescence. Telomeres can be elongated by the enzyme
      telomerase, which adds de novo telomere repeats to the ends of chromosomes.
      Mutations in genes for telomere binding proteins or components of telomerase give
      rise to the premature aging disorder dyskeratosis congenita (DC), which is
      characterized by extremely short telomeres and an aging phenotype. The current
      study demonstrates that DC cells signal a DNA damage response through p53 and its
      downstream mediator, p21(WAF/CIP), which is accompanied by an elevation in steady
      state levels of superoxide and percent glutathione disulfide, both indicators of
      oxidative stress. Poor proliferation of DC cells can be partially overcome by
      reducing O(2) tension from 21% to 4%. Further, restoring telomerase activity or
      inhibiting p53 or p21(WAF/CIP) significantly mitigated growth inhibition as well
      as caused a significant decrease in steady-state levels of superoxide. Our
      results support a model in which telomerase insufficiency in DC leads to
      p21(WAF/CIP) signaling, via p53, to cause increased steady-state levels of
      superoxide, metabolic oxidative stress, and senescence.

PMID- 21087146
TI  - Intrathecal lentiviral-mediated RNA interference targeting PKCgamma attenuates
      chronic constriction injury-induced neuropathic pain in rats.
AB  - In the spinal cord, protein kinase C isoform gamma (PKCgamma) plays an important
      role in the development of central pain sensitization. However, there are
      currently no specific PKCgamma inhibitors available. Therefore, the aim of the
      present study was to assess the role of PKCgamma in the modulation of pain using
      a more selective experimental tool. Although small interfering RNAs have been
      used to silence genes in neurons, in vivo delivery of RNA interference (RNAi)
      remains a major challenge, thus limiting its applications. Here we developed a
      highly efficient method of lentiviral-mediated delivery of short-hairpin RNAs
      targeting PKCgamma for in vivo gene silencing in the spinal cord of rats. This
      method decreased the expression of PKCgamma mRNA and protein, and additionally
      attenuated chronic constriction injury-induced mechanical allodynia and thermal
      hyperalgesia for more than 6 weeks. Our study suggests that PKCgamma is a
      potential RNAi target for neuropathic pain. Furthermore, the lentiviral vector
      delivery strategy holds great promise as a novel approach for the treatment of
      neuropathic pain and study of PKCgamma gene function.

PMID- 21087147
TI  - Evolution of synchronization and desynchronization in digital organisms.
AB  - We present a study in the evolution of temporal behavior, specifically
      synchronization and desynchronization, through digital evolution and group
      selection. In digital evolution, a population of self-replicating computer
      programs exists in a user-defined computational environment and is subject to
      instruction-level mutations and natural selection. Group selection links the
      survival of the individual to the survival of its group, thus encouraging
      cooperation. Previous approaches to engineering synchronization and
      desynchronization algorithms have taken inspiration from nature: In the well
      known firefly model, the only form of communication between agents is in the form
      of flash messages among neighbors. Here we demonstrate that populations of
      digital organisms, provided with a similar mechanism and minimal information
      about their environment, are capable of evolving algorithms for synchronization
      and desynchronization, and that the evolved behaviors are robust to message loss.
      We further describe how the evolved behavior for synchronization mimics that of
      the well-known Ermentrout model for firefly synchronization in biology. In
      addition to discovering self-organizing behaviors for distributed computing
      systems, this result indicates that digital evolution may be used to further our
      understanding of synchronization in biology.

PMID- 21087148
TI  - Noise and the evolution of neural network modularity.
AB  - We study the selective advantage of modularity in artificially evolved networks.
      Modularity abounds in complex systems in the real world. However, experimental
      evidence for the selective advantage of network modularity has been elusive
      unless it has been supported or mandated by the genetic representation. The
      evolutionary origin of modularity is thus still debated: whether networks are
      modular because of the process that created them, or the process has evolved to
      produce modular networks. It is commonly argued that network modularity is
      beneficial under noisy conditions, but experimental support for this is still
      very limited. In this article, we evolve nonlinear artificial neural network
      classifiers for a binary classification task with a modular structure. When noise
      is added to the edge weights of the networks, modular network topologies evolve,
      even without representational support.

PMID- 21087150
TI  - Identifying patterns from one-rule-firing cellular automata.
AB  - A new firing scheme for cellular automata in which only one rule is fired at a
      time produces myriad patterns. In addition to geometric patterns, natural
      patterns such as flowers and snow crystals were also generated. This study
      proposes an efficient method identifying the patterns using a minimal number of
      digits. Complexity of the generated patterns is discussed in terms of the shapes
      and colors of the patterns.

PMID- 21087151
TI  - Artificial cybernetic living individuals based on supramolecular-level
      organization as dispersed individuals.
AB  - One of the most characteristic features of spontaneously originating biological
      systems is that their most fundamental structure and especially functioning is
      based on molecular-level organization. This property is particularly important
      when natural living individuals composed of organic compounds of carbon are
      compared with (hypothetical) artificial living individuals based on metals,
      plastic, glass, silicon, and so on, whose most basic structural and functional
      units appear at the supramolecular level. The cybernetic definition of a living
      individual I proposed previously is used in the present work. I argue that
      artificial, supramolecular living individuals existing self-dependently in the
      environment of some distant planet must have the form of dispersed individuals
      composed of several separate subindividuals that are integrated functionally, but
      not structurally. These subindividuals would be analogous to such modules of
      human technical civilization as machines, robots, steelworks, chemical plants,
      electronic factories, power stations, and mines. Such dispersed individuals would
      resemble colonies of social insects and moles, which are also composed of
      separate subindividuals (particular insects and moles) carrying out different
      specialized functions.

PMID- 21087153
TI  - Discontinuous gas exchange in insects: is it all in their heads?
AB  - Some insects display an intermittent pattern of gas exchange while at rest, often
      going hours between breaths. These discontinuous gas exchange cycles (DGCs) are
      known to have evolved independently within five insect orders, but their possible
      adaptive benefit and evolutionary origin remain an enigma. Current research is
      primarily concerned with testing three adaptive hypotheses: that DGCs originally
      evolved or are currently maintained to (1) limit respiratory water loss, (2)
      enhance gas exchange in subterranean environments, or (3) limit oxidative damage.
      These adaptive explanations fail to unite a range of apparently contradictory
      observations regarding the insects that display DGCs and the conditions under
      which they occur. Here we argue that DGCs are explained by circadian,
      developmental, or artificially induced reductions in brain activity. We conclude
      that this pattern results from the thoracic and abdominal ganglia regulating
      ventilation in the absence of control from higher neural centers, and it is
      indicative of a sleeplike state.

PMID- 21087152
TI  - The therapeutic role of very low-density lipoprotein receptor gene in
      hyperlipidemia in type 2 diabetic rats.
AB  - Hyperlipidemia is a common feature of type 2 diabetes and is related to
      cardiovascular disease. The very low-density lipoprotein receptor (VLDLR) binds
      to and internalizes triglyceride-rich lipoproteins with high specificity. In this
      study, we evaluated the role of VLDLR in hyperlipidemia in type 2 diabetic rats.
      Type 2 diabetes was induced in male Wistar rats by injection of low-dose
      streptozotocin coupled with a high-fat diet. Recombinant adeno-associated viral
      (rAAV) vectors encoding the human VLDLR gene (rAAV.VLDLR) were intravenously
      administered to diabetic rats. Results showed that in vivo, total VLDLR mRNA and
      protein levels were significantly decreased in skeletal muscle (type I VLDLR
      mainly reduced) and adipose tissue (type II VLDLR mainly reduced) but not in
      heart in hypercholesterolemic, hypertriglyceridemic diabetic rats compared with
      normal rats. And in vitro, in 3T3-L1 adipocytes, insulin-induced (1.0 mmol/liter)
      insulin resistance significantly decreased VLDLR mRNA expression. In rats,
      rAAV.VLDLR delivery resulted in a reduction in serum cholesterol and triglyceride
      that lasted for the duration of the study (12 weeks). Fasting blood insulin was
      significantly lower in the rAAV.VLDLR group versus untreated diabetic rats
      although fasting blood glucose levels were not significantly different in both
      groups at the end of the study. rAAV.VLDLR-treated animals had significantly
      increased lipoprotein lipase activity and reduced aortic atherosclerosis. Taken
      together, our data suggest that type 2 diabetes and related insulin resistance
      manifest decreased VLDLR with elevated serum cholesterol and triglyceride levels,
      and overexpression of VLDLR through a single injection of rAAV.VLDLR reversed
      these effects and consequentially attenuated aorta atherosclerotic plaque
      progression.

PMID- 21087154
TI  - Placentation and maternal investment in mammals.
AB  - The mammalian placenta exhibits striking interspecific morphological variation,
      yet the implications of such diversity for reproductive strategies and fetal
      development remain obscure. More invasive hemochorial placentas, in which fetal
      tissues directly contact the maternal blood supply, are believed to facilitate
      nutrient transfer, resulting in higher fetal growth rates, and to be a state of
      relative fetal advantage in the evolution of maternal-offspring conflict. The
      extent of interdigitation between maternal and fetal tissues has received less
      attention than invasiveness but is also potentially important because it
      influences the surface area for exchange. We show that although increased
      placental invasiveness and interdigitation are both associated with shorter
      gestations, interdigitation is the key variable. Gestation times associated with
      highly interdigitated labyrinthine placentas are 44% of those associated with
      less interdigitated villous and trabecular placentas. There is, however, no
      relationship between placental traits and neonatal body and brain size. Hence,
      species with more interdigitated placentas produce neonates of similar body and
      brain size but in less than half the time. We suggest that the effects of
      placental interdigitation on growth rates and the way that these are traded off
      against gestation length may be promising avenues for understanding the
      evolutionary dynamics of parent-offspring conflict.

PMID- 21087155
TI  - Induced differentiation of neural stem cells of astrocytic origin to motor
      neurons in the rat.
AB  - Destruction of the motor neurons will lead to loss of innervation of the somatic
      muscle, which has long been considered an illness with no remedy. The only
      possible treatment is to substitute the injured motor neurons by neurons
      differentiated from stem cells. It has been recently reported that embryonic
      stems cells can be induced to differentiate to motor neurons. However, the use of
      embryonic stem cells has innate problems. The ideal source of motor neurons
      should be the cells from the patients themselves, which have the potential to be
      induced to motor neurons. Our previous study demonstrated that mature astrocyte
      has the potential of being dedifferentiated to neural stem cell. The present
      study was aimed to investigate if the neural stem cells of astrocytic origin can
      be induced to motor neurons. The results demonstrated that neural stem cells of
      astrocytic origin could be induced to differentiate into motor neurons and their
      progenitor cells with rich harvest. Further, it has been reported that astrocytes
      can be readily obtained via biopsy from the cerebral cortex of the patient,
      rendering autologous transplantation possible. In conclusion, matured astrocytes
      can be induced to motor neurons and be autologously transplanted to patients
      suffering from motor neuron destruction.

PMID- 21087145
TI  - Glutathione peroxidase-1 in health and disease: from molecular mechanisms to
      therapeutic opportunities.
AB  - Reactive oxygen species, such as superoxide and hydrogen peroxide, are generated
      in all cells by mitochondrial and enzymatic sources. Left unchecked, these
      reactive species can cause oxidative damage to DNA, proteins, and membrane
      lipids. Glutathione peroxidase-1 (GPx-1) is an intracellular antioxidant enzyme
      that enzymatically reduces hydrogen peroxide to water to limit its harmful
      effects. Certain reactive oxygen species, such as hydrogen peroxide, are also
      essential for growth factor-mediated signal transduction, mitochondrial function,
      and maintenance of normal thiol redox-balance. Thus, by limiting hydrogen
      peroxide accumulation, GPx-1 also modulates these processes. This review explores
      the molecular mechanisms involved in regulating the expression and function of
      GPx-1, with an emphasis on the role of GPx-1 in modulating cellular oxidant
      stress and redox-mediated responses. As a selenocysteine-containing enzyme, GPx-1
      expression is subject to unique forms of regulation involving the trace mineral
      selenium and selenocysteine incorporation during translation. In addition, GPx-1
      has been implicated in the development and prevention of many common and complex
      diseases, including cancer and cardiovascular disease. This review discusses the
      role of GPx-1 in these diseases and speculates on potential future therapies to
      harness the beneficial effects of this ubiquitous antioxidant enzyme.

PMID- 21087156
TI  - Characterization of a graded cervical hemicontusion spinal cord injury model in
      adult male rats.
AB  - Most experimental models of spinal cord injury (SCI) in rodents induce damage in
      the thoracic cord and subsequently examine hindlimb function as an indicator of
      recovery. In these models, functional recovery is most attributable to white
      matter preservation and is less influenced by grey-matter sparing. In contrast,
      most clinical cases of SCI occur at the lower cervical levels, a region in which
      both grey-matter and white-matter sparing contribute to functional motor
      recovery. Thus experimental cervical SCI models are beginning to be developed and
      used to assess protective and pharmacological interventions following SCI. The
      objective of this study was to characterize a model of graded cervical
      hemicontusion SCI with regard to several histological and behavioral outcome
      measures, including novel forelimb behavioral tasks. Using a commercially
      available rodent spinal cord impactor, adult male rats received hemicontusion SCI
      at vertebral level C5 at 100, 200, or 300 kdyn force, to produce mild, moderate,
      or severe injury severities. Tests of skilled and unskilled forelimb and
      locomotor function were employed to assess functional recovery, and spinal cord
      tissue was collected to assess lesion severity. Deficits in skilled and unskilled
      forelimb function and locomotion relating to injury severity were observed, as
      well as decreases in neuronal numbers, white-matter area, and white-matter
      gliosis. Significant correlations were observed between behavioral and
      histological data. Taken together, these data suggest that the forelimb
      functional and locomotor assessments employed here are sensitive enough to
      measure functional changes, and that this hemicontusion model can be used to
      evaluate potential protective and regenerative therapeutic strategies.

PMID- 21087158
TI  - Raman spectroscopic analysis of a desert cyanobacterium Nostoc sp. in response to
      UVB radiation.
AB  - Cyanobacteria are capable of tolerating environmental extremes. To survive in
      extreme environments, cyanobacteria have developed the capability to adapt to a
      variety of stresses. For example, cyanobacteria have adopted a number of
      strategies with which to survive UV stress, including expression of UV-screening
      pigments and antioxidant systems. We have previously shown that several
      antioxidants are significantly expressed in Nostoc sp. by UVB irradiation. We
      report here that the content of UV-responsive biomarkers such as beta-carotene
      and scytonemin can be easily detected by Fourier transform Raman spectroscopy
      with use of a small sample size and that the content of beta-carotene is
      dependant on the UVB intensity and exposure time. Our results indicate that Raman
      spectroscopy may be a helpful tool to analyze UV-protective molecules of
      cyanobacterium in astrobiological studies without access to large sample sizes
      and complicated extractions, which are needed by other analytical techniques such
      as high-performance liquid chromatography and mass spectrometry.

PMID- 21087157
TI  - The formation of sulfate and elemental sulfur aerosols under varying laboratory
      conditions: implications for early earth.
AB  - The presence of sulfur mass-independent fractionation (S-MIF) in sediments more
      than 2.45 * 10(9) years old is thought to be evidence for an early anoxic
      atmosphere. Photolysis of sulfur dioxide (SO(2)) by UV light with lambda < 220 nm
      has been shown in models and some initial laboratory studies to create a S-MIF;
      however, sulfur must leave the atmosphere in at least two chemically different
      forms to preserve any S-MIF signature. Two commonly cited examples of chemically
      different sulfur species that could have exited the atmosphere are elemental
      sulfur (S(8)) and sulfuric acid (H(2)SO(4)) aerosols. Here, we use real-time
      aerosol mass spectrometry to directly detect the sulfur-containing aerosols
      formed when SO(2) either photolyzes at wavelengths from 115 to 400 nm, to
      simulate the UV solar spectrum, or interacts with high-energy electrons, to
      simulate lightning. We found that sulfur-containing aerosols form under all
      laboratory conditions. Further, the addition of a reducing gas, in our
      experiments hydrogen (H(2)) or methane (CH(4)), increased the formation of S(8).
      With UV photolysis, formation of S(8) aerosols is highly dependent on the initial
      SO(2) pressure; and S(8) is only formed at a 2% SO(2) mixing ratio and greater in
      the absence of a reductant, and at a 0.2% SO(2) mixing ratio and greater in the
      presence of 1000 ppmv CH(4). We also found that organosulfur compounds are formed
      from the photolysis of CH(4) and moderate amounts of SO(2). The implications for
      sulfur aerosols on early Earth are discussed. Key Words: S-MIF-Archean atmosphere
      Early Earth-Sulfur aerosols.

PMID- 21087159
TI  - Implications of subzero metabolic activity on long-term microbial survival in
      terrestrial and extraterrestrial permafrost.
AB  - The survival of microorganisms over extended time frames in frozen subsurface
      environments may be limited by chemical (i.e., via hydrolysis and oxidation) and
      ionizing radiation-induced damage to chromosomal DNA. In an effort to improve
      estimates for the survival of bacteria in icy terrestrial and extraterrestrial
      environments, we determined rates of macromolecular synthesis at temperatures
      down to -15 degrees C in bacteria isolated from Siberian permafrost
      (Psychrobacter cryohalolentis K5 and P. arcticus 273-4) and the sensitivity of P.
      cryohalolentis to ionizing radiation. Based on experiments conducted over ~400
      days at -15 degrees C, the rates of protein and DNA synthesis in P.
      cryohalolentis were <1 to 16 proteins cell(-1) d(-1) and 83 to 150 base pairs
      (bp) cell(-1) d(-1), respectively; P. arcticus synthesized DNA at rates of 20 to
      1625 bp cell(-1) d(-1) at -15 degrees C under the conditions tested. The dose of
      ionizing radiation at which 37% of the cells survive (D(37)) of frozen
      suspensions of P. cryohalolentis was 136 Gy, which was ~2-fold higher (71 Gy)
      than identical samples exposed as liquid suspensions. Laboratory measurements of
      [(3)H]thymidine incorporation demonstrate the physiological potential for DNA
      metabolism at -15 degrees C and suggest a sufficient activity is possible to
      offset chromosomal damage incurred in near-subsurface terrestrial and martian
      permafrost. Thus, our data imply that the longevity of microorganisms actively
      metabolizing within permafrost environments is not constrained by chromosomal DNA
      damage resulting from ionizing radiation or entropic degradation over geological
      time.

PMID- 21087160
TI  - Design, fabrication, and test of a hydrothermal reactor for origin-of-life
      experiments.
AB  - We describe a continuous high-pressure flow reactor designed to simulate the
      unforced convective interaction of hydrothermal solutions and ocean waters with
      submarine crust on early Earth-conditions appropriate to those that may have led
      to the onset of life. The experimental operating conditions are appropriate for
      investigating kinetic hydrothermal processes in the early history of any sizable
      wet, rocky planet. Beyond the description of the fabrication, we report an
      initial experiment that tested the design and investigated the feasibility of
      sulfide and silica dissolution in alkaline solution from iron sulfide and
      basaltic rock, and their possible subsequent transport as HS(-) and H(2)SiO(2
      )(4) in hot alkaline solutions. Delivery of hydrogen sulfide and dihydrogen
      silicate ions would have led to the precipitation of ferrous hydroxide,
      hydroxysilicates, and iron sulfides as integral mineral components of an off
      ridge compartmentalized hydrothermal mound in the Hadean. Such a mound could, we
      contend, have acted as a natural chemical and electrochemical reactor and,
      ultimately, as the source of all biochemistry on our planet. In the event, we
      show that an average of ~1 mM/kg of both sulfide and silica were released
      throughout, though over 10 mM/kg of HS(-) was recorded for ~100 minutes in the
      early stages of the experiment. This alkaline effluent from the reactor was
      injected into a reservoir of a simulacrum of ferrous iron-bearing "Hadean Ocean"
      water in an experiment that demonstrated the capacity of such fluids to generate
      hydrothermal chimneys and a variety of contiguous inorganic microgeode
      precipitates bearing disseminations of discrete metal sulfides. Comparable
      natural composite structures may have acted as hatcheries for emergent life in
      the Hadean.

PMID- 21087161
TI  - Thyroid cell growth: sphingomyelin metabolism as non-invasive marker for cell
      damage acquired during spaceflight.
AB  - Prolonged spaceflights are known to elicit changes in human cardiovascular,
      musculoskeletal, and nervous systems, whose functions are regulated by the
      thyroid gland. It is known that sphingomyelin metabolism is involved in apoptosis
      (programmed cell death) of thyroid cells induced by UVC radiation, but at present
      no data exists with regard to this phenomenon, which occurs during space
      missions. The aim of this study was to analyze, for the first time, the effect of
      spaceflight on the enzymes of sphingomyelin metabolism, sphingomyelinase, and
      sphingomyelin synthase, and to determine whether the ratio between the two
      enzymes might be used as a possible marker for thyroid activity during space
      missions. Both quiescent thyroid cells and thyroid cells stimulated to
      proliferate with thyrotropin (TSH) were cultured during the Eneide and Esperia
      missions on the International Space Station. The results show that during space
      missions the cells treated with TSH grew only 1.5 +/- 0.65-fold and, thus, behave
      similarly to quiescent cells, while on the ground the same cells, maintained in
      experimental conditions that reproduced those of the flight, grew 7.71 +/- 0.67
      fold. Comparison of the sphingomyelinase/sphingomyelin-synthase ratio and the
      levels of Bax, STAT3, and RNA polymerase II in proliferating, quiescent, pro
      apoptotic, or apoptotic cells demonstrated that thyroid cells during space
      missions were induced into a pro-apoptotic state. Given its specificity and the
      small amount of cells needed for analysis, we propose the use of the
      sphingomyelinase/sphingomyelin-synthase ratio as a marker of functional status of
      thyroid cells during space missions. Further studies could lead to its use in
      real time during prolonged spaceflights.

PMID- 21087162
TI  - Astrobiology through the ages of Mars: the study of terrestrial analogues to
      understand the habitability of Mars.
AB  - Mars has undergone three main climatic stages throughout its geological history,
      beginning with a water-rich epoch, followed by a cold and semi-arid era, and
      transitioning into present-day arid and very cold desert conditions. These global
      climatic eras also represent three different stages of planetary habitability: an
      early, potentially habitable stage when the basic requisites for life as we know
      it were present (liquid water and energy); an intermediate extreme stage, when
      liquid solutions became scarce or very challenging for life; and the most recent
      stage during which conditions on the surface have been largely uninhabitable,
      except perhaps in some isolated niches. Our understanding of the evolution of
      Mars is now sufficient to assign specific terrestrial environments to each of
      these periods. Through the study of Mars terrestrial analogues, we have assessed
      and constrained the habitability conditions for each of these stages, the
      geochemistry of the surface, and the likelihood for the preservation of organic
      and inorganic biosignatures. The study of these analog environments provides
      important information to better understand past and current mission results as
      well as to support the design and selection of instruments and the planning for
      future exploratory missions to Mars.

PMID- 21087163
TI  - Setting a standard: the limulus amebocyte lysate assay and the assessment of
      microbial contamination on spacecraft surfaces.
AB  - Historically, colony-forming units as determined by plate cultures have been the
      standard unit for microbiological analysis of environmental samples, medical
      diagnostics, and products for human use. However, the time and materials required
      make plate cultures expensive and potentially hazardous in the closed
      environments of future NASA missions aboard the International Space Station and
      missions to other Solar System targets. The Limulus Amebocyte Lysate (LAL) assay
      is an established method for ensuring the sterility and cleanliness of samples in
      the meat-packing and pharmaceutical industries. Each of these industries has
      verified numerical requirements for the correct interpretation of results from
      this assay. The LAL assay is a rapid, point-of-use, verified assay that has
      already been approved by NASA Planetary Protection as an alternate, molecular
      method for the examination of outbound spacecraft. We hypothesize that standards
      for molecular techniques, similar to those used by the pharmaceutical and meat
      packing industries, need to be set by space agencies to ensure accurate data
      interpretation and subsequent decision making. In support of this idea, we
      present research that has been conducted to relate the LAL assay to plate
      cultures, and we recommend values obtained from these investigations that could
      assist in interpretation and analysis of data obtained from the LAL assay.

PMID- 21087164
TI  - A comment on "the far future of exoplanet direct characterization"--the case for
      interstellar space probes.
AB  - Following on from ideas presented in a recent paper by Schneider et al. on "The
      Far Future of Exoplanet Direct Characterization," I argue that they have
      exaggerated the technical obstacles to performing such "direct characterization"
      by means of fast (order 0.1c) interstellar space probes. A brief summary of rapid
      interstellar spaceflight concepts that may be found in the literature is
      presented. I argue that the presence of interstellar dust grains, while certainly
      something that will need to be allowed for in interstellar vehicle design, is
      unlikely to be the kind of showstopper suggested by Schneider et al. Astrobiology
      as a discipline would be a major beneficiary of developing an interstellar
      spaceflight capability, albeit in the longer term, and I argue that
      astrobiologists should keep an open mind to the possibilities.

PMID- 21087166
TI  - Comparison of induction of labor with vaginal misoprostol plus oxytocin versus
      oxytocin alone in term primigravidae.
AB  - OBJECTIVE: To compare the efficacy and complications of intravaginal misoprostol
      application before starting oxytocin infusion with oxytocin infusion alone for
      labor induction in term primigravidae pregnancies with low-Bishop score. METHODS:
      This randomized study included 101 primigravidae women with singleton pregnancies
      >38 weeks and a Bishop score of <6. Group 1 (50 patients) received a 50-MUg dose
      of intravaginal misoprostol, with an oxytocin infusion started 3 h later. Group 2
      (51 patients) received only an oxytocin infusion for labor induction. The time
      from induction to delivery, the route of delivery and complications were
      analyzed. RESULTS: The mean time from induction to delivery was 10.4 +/- 2.1 h in
      Group 1 and 13.7 +/- 3.4 in Group 2 (p < 0.001). The rates of vaginal delivery,
      Apgar scores at 1st and 5th min, placental abruption, and postpartum hemorrhage
      were similar between the two groups. CONCLUSION: Intravaginal application of 50
      MUg misoprostol before starting oxytocin infusion is a more effective method of
      labor induction than oxytocin infusion alone in term primigravidae pregnant women
      with low-Bishop scores.

PMID- 21087167
TI  - Nuclear magnetic resonance spectroscopy-based metabonomic investigation of
      biochemical effects in serum of gamma-irradiated mice.
AB  - PURPOSE: Radiation exposure induces change in many biological compounds. It is
      important to assess the physiological and biochemical response to an absorbed
      dose of ionising radiation due to intentional or accidental event and to predict
      medical consequences for medical management. In the present study, nuclear
      magnetic resonance (NMR) spectroscopy-based metabolic profiling was used in mice
      serum for identification of radiation-induced changes at metabolite level.
      MATERIALS AND METHODS: Mice were irradiated with 3, 5 and 8 Gray of gamma
      radiation dose and serum samples collected at day 1, 3 and 5 post irradiation
      were analysed by proton nuclear magnetic resonance (1H NMR) spectroscopy. 1H NMR
      spectra of serum were analysed by pattern recognition using principal component
      analysis. RESULTS: Irradiated mice serum showed distinct metabonomic phenotypes
      and revealed dose- and time-dependent clustering of irradiated groups. 1H NMR
      spectral analysis exhibited increased lactate, amino acids, choline and lipid
      signals as well as decreased glucose signals. These findings indicate radiation
      induced disturbed energy, lipid and protein metabolism. CONCLUSIONS: The
      information obtained from this study reflects multiple physiological
      dysfunctions. The study promises the application of NMR-based metabonomics in the
      field of radiobiology, for development of metabolic-based markers for screening
      of risk populations and medical management in these cases.

PMID- 21087168
TI  - Protection by methylproamine of irradiated human keratinocytes correlates with
      reduction of DNA damage.
AB  - PURPOSE: The therapeutic ratio for ionising radiation treatment of tumour is a
      trade-off between normal tissue side-effects and tumour control. Application of a
      radioprotector to normal tissue can reduce side-effects. Here we study the
      effects of a new radioprotector on the cellular response to radiation.
      Methylproamine is a DNA-binding radioprotector which, on the basis of published
      pulse radiolysis studies, acts by repair of transient radiation-induced oxidative
      species on DNA. To substantiate this hypothesis, we studied protection by
      methylproamine at both clonogenic survival and radiation-induced DNA damage,
      assessed by gammaH2AX (histone 2AX phosphorylation at serine 139) focus formation
      endpoints. MATERIALS AND METHODS: The human keratinocyte cell line FEP1811 was
      used to study clonogenic survival and yield of gammaH2AX foci following
      irradiation (137Cs gamma-rays) of cells exposed to various concentrations of
      methylproamine. Uptake of methylproamine into cell nuclei was measured in
      parallel. RESULTS: The extent of radioprotection at the clonogenic survival
      endpoint increased with methylproamine concentration up to a maximum dose
      modification factor (DMF) of 2.0 at 10 MUM. At least 0.1 fmole/nucleus of
      methylproamine is required to achieve a substantial level of radioprotection (DMF
      of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The
      gammaH2AX focus yield per cell nucleus 45 min after irradiation decreased with
      drug concentration with a DMF of 2.5 at 10 MUM. CONCLUSIONS: These results are
      consistent with the hypothesis that radioprotection by methylproamine is mediated
      by attenuation of the extent of initial DNA damage.

PMID- 21087169
TI  - Structural chromosomal aberrations, aneuploidy, and mosaicism in early cleavage
      mouse embryos derived from spermatozoa exposed to gamma-rays.
AB  - PURPOSE: To quantitatively and qualitatively investigate the changes in
      chromosomal aberrations during early cleavage in mouse embryos derived from gamma
      irradiated spermatozoa. MATERIALS AND METHODS: Mature males were exposed to 2 Gy
      or 4 Gy of 137Cs gamma-rays, and their spermatozoa were used to produce embryos
      via in vitro fertilisation (IVF). The metaphase chromosomes were prepared from
      one-cell, two-cell, and four-cell embryos. In the chromosome preparations from
      two-cell and four-cell embryos, the separation of the sister blastomeres was
      precluded by treatment of the embryos with concanavalin A. The incidence of
      embryos with structural chromosomal aberrations, aneuploidy, or mosaicism was
      estimated. The fates of the different types of gamma-ray-induced structural
      chromosomal aberrations were also investigated in those embryos. RESULTS: The
      exposure of spermatozoa to 2 Gy or 4 Gy gamma-rays caused structural chromosomal
      aberrations in 25.9% and 35.7% of the resultant one-cell embryos, respectively.
      At two-cell embryonic stage, the incidence of structural chromosomal aberrations
      was 17.4% in the 2 Gy group and 27.1% in the 4 Gy group. At the four-cell
      embryonic stage, although the incidence of control embryos with structural
      chromosomal aberrations was considerably high, the net incidence of embryos with
      radiation-induced structural chromosomal aberrations was similar to that at the
      one-cell stage. The incidence of aneuploidy was high in two-cell and four-cell
      embryos after both doses of gamma-rays. The incidence of mosaicism increased
      significantly in dose- and embryonic-stage-dependent manners. Anaphase lag, and
      the degeneration and non-disjunction of the aberrant chromosomes were frequently
      observed in aneuploid and mosaic embryos. CONCLUSIONS: Mouse sperm DNA is highly
      vulnerable to gamma-rays. The structural chromosomal aberrations of sperm origin
      are unstable in their behaviour and structure during cleavage, and therefore
      cause secondary aneuploidy and mosaicism in the early cleavage embryos.

PMID- 21087170
TI  - The influence of irradiation on the potential chondroprotective effect of aqueous
      extract of propolis in rats.
AB  - PURPOSE: Cartilage degradation usually results as a consequence of inflammatory
      processes in the joints. To study this phenomenon experimentally, adjuvant
      induced arthritis (AIA) was used as a model of chronic inflammation under the
      influence of irradiation. The potential chondroprotective effect of 13% aqueous
      extract of propolis (AEP) in arthritic rats was investigated. MATERIALS AND
      METHODS: The influence of whole body irradiation on the arthritic inflammatory
      response was investigated by subjecting rats to a Gamma source before the
      induction of arthritis. 13% AEP was injected intraperitoneally in a dose of 5
      ml/kg and diclofenac was used as reference non-steroidal anti-inflammatory drug
      (NSAID) in a dose of 3 mg/kg. The chosen parameters for cartilage integrity were
      glycosaminoglycan (GAG), hydroxyproline contents in cartilage and cartilage
      oligomeric matrix protein (COMP) in serum. The serum levels of tumour necrosis
      factor-alpha (TNF-alpha), nitric oxide (NO) and the oxidative stress biomarkers
      such as blood glutathione (GSH) and plasma malondialdehyde (MDA) levels. RESULTS:
      Induction of arthritis led to a reduction in GAG and hydroxyproline content of
      femoral cartilage and a corresponding rise in COMP in serum. Previous exposure to
      irradiation resulted in a milder reduction of GAG and hydroxyproline and a lesser
      rise in COMP. Treatment of arthritic irradiated and non-irradiated rats with 13%
      AEP markedly prevented the breakdown of cartilage in a much more effective manner
      than diclofenac. Both AEP and diclofenac were equipotent in reducing the level of
      TNF-alpha and were able to normalize NO and the oxidative stress biomarkers in
      non-irradiated and irradiated arthritic rats. CONCLUSION: The ability of propolis
      to protect cartilage degradation could therefore prove of value in the treatment
      of chronic arthritic diseases, offering an advantage over some NSAID,
      particularly those with a potential detrimental effect on cartilage integrity.

PMID- 21087171
TI  - Germline minisatellite mutations in survivors of childhood and young adult cancer
      treated with radiation.
AB  - PURPOSE: To investigate minisatellite germline mutation rates in survivors of
      childhood and young adult cancer who received radiotherapy. MATERIALS AND
      METHODS: DNA samples from 100 families, where one parent was a cancer survivor,
      were analysed for mutations at eight hypervariable minisatellite loci (B6.7,
      CEB1, CEB15, CEB25, CEB36, MS1, MS31, MS32) by Southern hybridisation. RESULTS:
      No significant difference was observed between the paternal mutation rate of 5.6%
      in exposed fathers with a mean preconceptional testicular dose of 1.23 Gy (56
      mutations in 998 informative alleles) and that of 5.8% in unexposed fathers (17
      in 295 informative alleles). Subgrouping the exposed fathers into dose groups of
      < 0.10 Gy, 0.10-0.99 Gy, 1.00-1.99 Gy, >= 2.00 Gy revealed no significant
      differences in paternal mutation rate in comparison with the unexposed fathers.
      Maternal mutation rates of 1.6% in cancer survivor mothers with a mean
      preconceptional ovarian dose of 0.58 Gy (five mutations in 304 informative
      alleles) and 2.1% in unexposed mothers (21 in 987 informative alleles) were not
      significantly different. There were no differences in minisatellite mutation
      rates associated with treatment with chemotherapeutic agents. CONCLUSIONS: This
      study provides evidence that preconception radiotherapy for childhood or early
      adulthood cancer does not increase the germline minisatellite mutation rate.

PMID- 21087172
TI  - Impact of metabolic syndrome on erectile dysfunction and lower urinary tract
      symptoms in benign prostatic hyperplasia patients.
AB  - INTRODUCTION: The aim of this study was to investigate the relationship among
      metabolic syndrome (MetS), erectile dysfunction (ED) and lower urinary tract
      symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). METHODS: Our
      study included 106 patients with BPH, 33 (31.1%) of whom had MetS. Blood
      pressures, waist circumferences, serum levels of fasting blood glucose, high
      density lipoprotein and triglyceride of patients were recorded. Erectile
      functions of the patients were evaluated by International Index of Erectile
      Function (IIEF). Patients were divided into two groups according to IIEF scores,
      namely 'mild/no ED' and 'moderate/severe ED'. IIEF scores of ED groups were
      between 17 and 30 and 6-16 in turn. LUTS severities were assessed by
      International Prostate Symptom Score (IPSS) and classified as mild (IPSS 0-7),
      moderate (IPSS 8-19) and severe (IPSS 20-35). RESULTS: There was a significant
      difference between ED groups concerning MetS presence (p=0.032). MetS presence
      was not found to be associated with the severity of LUTS (p=0.144). There was no
      correlation between ED groups regarding LUTS severity (p=0.303). CONCLUSION:
      Results of the present study showed a correlation between MetS presence and ED.
      In the light of our results, MetS seems to play an important role in the
      etiopathogenesis of ED in patients with BPH.

PMID- 21087173
TI  - Thyroid cancer in older men.
AB  - This article reviews most common types of thyroid cancer focusing on older males
      worldwide. Thyroid carcinoma is the most common endocrine malignancy. It includes
      tumour types that range from localised papillary carcinomas to lethal anaplastic
      disease. Among elderly population, male gender seems to be highly correlated with
      the risk and aggressiveness of thyroid cancer. Early diagnosis and urgent
      aggressive treatment are important for aging patients. This article includes
      numerous studies which evaluate prevalence, morbidity and mortality of thyroid
      cancer in older males.

PMID- 21087174
TI  - Inverse association between total testosterone concentrations, incident
      hypertension and blood pressure.
AB  - BACKGROUND: Studies on the relationship between testosterone concentrations and
      blood pressure have yielded inconsistent results. Therefore, this study
      investigated the prospective association of total testosterone (TT)
      concentrations with risk of incident hypertension and blood pressure change in
      1,484 men aged 20-79 years. METHODS: Data from the population-based Study of
      Health in Pomerania, Germany, were used. Serum TT concentrations, measured by
      chemiluminescent enzyme immunoassays, were categorised into age-specific
      quartiles. Generalised Estimating Equation (GEE) models, adjusted for age, waist
      circumference, physical activity, smoking and alcohol consumption were specified.
      RESULTS: During a median follow-up time of 5.0 years, the prevalence of
      hypertension increased from 50.6% to 57.1%. TT concentrations were significantly
      lower in men with baseline and incident hypertension. Analyses revealed that men
      with baseline TT concentrations in the lowest quartile had an increased risk of
      incident hypertension (odds ratio (OR), 1.19 (95% CI, 1.10-1.28)) compared to men
      with higher TT concentrations. Furthermore, we found a significant inverse
      association of TT concentrations and blood pressure, showing that men with
      baseline TT concentrations in the lowest quartile showed the slightest change in
      systolic blood pressure (-6.01 mmHg), diastolic blood pressure (-2.11 mmHg) and
      pulse pressure (-3.98 mmHg). Sensitivity analyses in a subpopulation of men
      without antihypertensive medication confirmed these findings. CONCLUSION: These
      results show that low male TT concentrations are predictive of hypertension,
      suggesting TT as a potential biomarker of increased cardiovascular risk.

PMID- 21087175
TI  - The development of anti-cancer programs in Canada for the geriatric population:
      an integrated nursing and medical approach.
AB  - Cancer control in Canada refers to the development of comprehensive programs
      utilising modern techniques, tools and approaches that actively prevent, cure or
      manage cancer. The scope of such programs is quite vast. They range from
      prevention, early detection and screening, comprehensive treatment both curative
      and palliative to comprehensive palliative care. Cancer is a disease associated
      with the aging population, and as the population ages the incidence of cancer
      would be expected to rise as well. This in itself poses a great challenge. In
      addition, the aging population demographics with the projected rise in the
      numbers of senior citizens, especially the over 80 group in the next decade,
      poses its own creative challenges to health planners. In Canada, health care is
      centrally administered, and controlled by the provincial governments of Canada,
      under the Canada Health Act. The challenge of developing comprehensive programs
      for the geriatric population requires changes in the care models and care
      pathways. The patient-centred models that have been adapted require a
      multidisciplinary approach to the clientele and their families that integrates
      cancer therapy and geriatric care and realities. This requires changes in the
      nursing and medical approach, as well as education in the subtleties of the two
      intersecting medical realities.

PMID- 21087176
TI  - More than half of the men in a Swedish population of men aged 55, 65 and 75
      believe in 'a male climacteric'.
AB  - AIM: Symptoms of late-onset hypogonadism (LOH) are often unspecific, and the
      existence of a male climacteric has been much debated. In this study, we
      investigate aging men's thoughts about, and beliefs, in a 'male climacteric'.
      METHODS: A questionnaire was developed including background demographic data,
      symptoms possibly related to LOH and questions about men's thoughts and beliefs
      in a 'male climacteric'. All men, 55-, 65- and 75-years old, living in Linkoping,
      Sweden (n=1885) received the questionnaire. RESULTS: One thousand three hundred
      fifty-six (72%) questionnaires were eligible for evaluation, 65.4% of the
      responders had heard of a 'male climacteric', and 42.2% believed it existed but
      only 3% had sought medical advice for these symptoms. More than half believed
      that a 'male climacteric' was related to decreased libido and less strong
      erections. Almost half of the men thought that decreased memory and/or dystymia
      and anxiousness were related to a male climacteric. CONCLUSIONS: The majority of
      men have heard of a male climacteric, but only a minority had consulted a
      practitioner about their symptoms. More information and knowledge are needed, for
      the general population to better motivate men to seek medical advice and also for
      the health care professionals to better deal with the symptoms of LOH.

PMID- 21087177
TI  - Genotypic characteristics of HIV type 1 based on gp120 hypervariable region 3 of
      isolates from Southern Brazil.
AB  - The aim of this study was to investigate HIV-1 molecular diversity and the
      epidemiological profile of HIV-1-infected patients from Ribeirao Preto, Brazil. A
      nested PCR followed by sequencing of a 302-base pair fragment of the env gene (C2
      V3 region) was performed in samples from HIV-1-positive patients. A total of 45
      sequences were aligned with final manual adjustments. The phylogenetic analyses
      showed a higher prevalence of HIV-1 subtype B in the studied population (97.8%)
      with only one sample yielding an F1 subtype. The viral genotyping prediction
      showed that CCR5 tropism was the most prevalent in the studied cohort. Geno2pheno
      analysis showed that R5 and CXCR4 prediction were 69% and 31%, respectively.
      There was no statistical significance, either in viral load or in CD4(+) T cell
      count when R5 and X4 prediction groups were compared. Moreover, the GPGR tetramer
      was the most common V3 loop core motif identified in the HIV-1 strains studied
      (34.1%) followed by GWGR, identified in 18.1% of the samples. The high level of B
      subtype in this Brazilian population reinforces the nature of the HIV epidemic in
      Brazil, and corroborates previous data obtained in the Brazilian HIV-infected
      population.

PMID- 21087178
TI  - Highlight: xenobiotics and cell signaling.

PMID- 21087182
TI  - The skin is the body's largest organ.

PMID- 21087183
TI  - Routine recording of dermoscopic images as an aid to diagnosis.
AB  - Dermoscopy has been described as a useful tool for the early diagnosis of
      malignant melanoma. The authors were asked to routinely produce high-quality
      Dermoscopic images which could be used at Dermatology Multi-disciplinary team
      meetings as an aid in the evaluation of moles on patients. The process
      facilitating this procedure is described.

PMID- 21087184
TI  - Teledermatology - the Cardiff experience.
AB  - This paper describes the development and on-going management of an email-based
      teledermatology service, providing General Practitioners in the metropolitan area
      of Cardiff, UK, with rapid access to a hospital-based Consultant Dermatologist.
      The paper describes the ethos behind the establishment of the service, details
      the equipment and methods used to deliver it, and presents results from the first
      four years of operation. It also discusses the lessons learnt in moving from an
      initial pilot to a supported service.

PMID- 21087187
TI  - Vitiligo.

PMID- 21087188
TI  - The use of dermoscopy in medical photography for the early detection of skin
      cancer.

PMID- 21087191
TI  - Photography in dermatology: a dermatologist's perspective.

PMID- 21087193
TI  - Inhibition of lipoxygenase (LOX) and anticancer activity caused by gold(I) mixed
      ligands complexes of triphenylphosphine and thioamides.
AB  - Four mixed ligand gold(I) complexes with the thioamides 2-mercapto-thiazolidine
      (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole
      (ClmbztH) and triphenylphosphine (tpp) of formulae [Au(tpp)Cl] (1)
      [Au(tpp)(mtzd)] (2), [Au(tpp)(mbzt)] (3) and [Au(tpp)(Clmbzt)] (4), already
      known, were used to study their mechanism of inhibition activity towards the
      catalytic oxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme
      lipoxygenase (LOX), kinetically and theoretically. The results are compared to
      those of cisplatin. In addition, the anticancer cell screening results against
      leimyosarcoma (LMS) cells have shown that 2-4 complexes were more active than
      cisplatin. The uptake of complexes in LMS cells were also studied with
      electrospray ionisation mass spectrometry spectroscopy.

PMID- 21087195
TI  - Early-onset progressive myoclonic epilepsy with dystonia mapping to 16pter-p13.3.
AB  - The authors present three patients from a consanguineous family afflicted with
      novel recessive myoclonic epilepsy characterized by very early onset and a
      steadily progressive course. The onset is in early infancy, and death occurs in
      the first decade. In addition to various types of myoclonic seizures, episodic
      phenomena such as dystonias, postictal enduring hemipareses, autonomic
      involvements, and periods of obtundation and lethargy were also observed.
      Developmental and neurological retardation, coupled with systemic infections,
      leads to a full deterioration. The authors designated the disease progressive
      myoclonic epilepsy with dystonia (PMED). A genome scan for the family and
      subsequent fine mapping localized the gene responsible for the disease to the
      most telomeric 6.73 mega base pairs at the p-terminus of chromosome 16, with a
      maximum multipoint logarithm-of-odds score of 7.83 and a maximum two-point score
      of 4.25. A candidate gene was analyzed for mutations in patients, but no mutation
      was found.

PMID- 21087194
TI  - Selection of behaviors and segmental coordination during larval locomotion is
      disrupted by nuclear polyglutamine inclusions in a new Drosophila Huntington's
      disease-like model.
AB  - Huntington's disease is an autosomal dominant neurodegenerative disorder that is
      caused by abnormal expansion of a polyglutamine tract in the huntingtin protein,
      resulting in intracellular aggregate formation and neurodegeneration. How
      neuronal cells are affected by such a polyglutamine tract expansion remains
      obscure. To dissect the ways in which polyglutamine expansion can cause neural
      dysfunction, the authors generated Drosophila transgenic strains expressing
      either a nuclear targeted or cytoplasmic form of pathogenic (NHtt-152Q(NLS), NHtt
      152Q), or nonpathogenic (NHtt-18Q(NLS), NHtt-18Q) N-terminal human huntingtin.
      These proteins were expressed in the dendritic arborization neurons of the larval
      peripheral nervous system and their effects on neuronal survival, morphology, and
      larval locomotion were examined. The authors found that NHtt-152Q(NLS) larvae had
      altered dendrite morphology and larval locomotion, whereas NHtt-152Q, NHtt
      18Q(NLS), and NHtt-18Q larvae did not. Furthermore, the authors examined the
      physiological defect underlying this disrupted larval locomotion in detail by
      recording spontaneous ongoing segmental nerve activity. NHtt-152Q(NLS) larvae
      displayed uncoordinated activity between anterior and posterior segments.
      Moreover, anterior segments had shorter bursts and longer interburst intervals in
      NHtt-152Q(NLS) larvae than in NHtt-18Q(NLS) larvae, whereas posterior segments
      had longer bursts and shorter interburst intervals. These results suggest that
      the pathogenic protein disrupts neuron function without inducing cell death, and
      describe how this dysfunction leads to a locomotor defect. These results also
      suggest that sensory inputs are necessary for the coordination of anterior and
      posterior body parts during locomotion. From these analyses the authors show that
      examination of motor behaviors in the Drosophila larvae is a powerful new model
      to dissect non-cell-lethal mechanisms of mutant Htt toxicity.

PMID- 21087196
TI  - Recent HIV type 1 infection among participants in a same-day mobile testing pilot
      study in Zimbabwe.
AB  - We estimated HIV-1 incidence and characterized risk factors associated with
      recent infection among participants of a mobile HIV voluntary counseling and
      testing (VCT) pilot program in two communities in Zimbabwe (N = 1096). HIV-1
      infection was diagnosed using a parallel rapid testing algorithm. Recent HIV-1
      infections were characterized using the BED immunoglobulin G capture enzyme
      immunoassay (BED-CEIA). HIV prevalence was 28.9% overall and nearly twice as high
      in women compared to men (39.5% vs. 21.4%, p < 0.001). HIV-1 incidence was 1.91%
      and was comparable between men and women (1.99% vs.1.88%; p = 0.626). Although
      not significant, the proportion of recent infections among all infections was
      highest among persons ages 25 to 34 years old (10.5%) for both men (11.9%) and
      women (9.2%). Persons recently infected compared to those with long-term
      infections were more likely to report STD symptoms (33% vs. 13%; OR = 3.2; p =
      0.075) and prior STD treatment (13% vs. 6%; OR = 3.4; p = 0.187) in the previous
      6 months. There were no associations found between recent versus long-term HIV
      infection status and perceived risk or expectation of negative test results.
      Recent HIV-1 infection detection among mobile VCT participants is a valuable
      measure for tracking the spread of the epidemic among persons who might otherwise
      not have access to HIV testing due to practical and logistical barriers. Mobile
      VCT presents opportunities to expand HIV testing services and evaluate at-risk
      populations within community settings. Given the challenges of longitudinal
      cohort studies, recent infection may be a practical endpoint for community-based
      prevention intervention trials employing mobile testing.

PMID- 21087197
TI  - Lack of high-level resistance mutations in HIV type 1 BF recombinant strains
      circulating in northeast Brazil.
AB  - Abstract The genetic variability and the prevalence of drug resistance-associated
      mutations (DRAM) of HIV-1 isolates from 50 women and 8 children from Feira de
      Santana, Bahia, Brazil were investigated. DNA samples were obtained and pol
      sequences were generated by PCR and direct sequencing. Phylogenetic analysis
      showed that 39 (67.2%) samples were subtype B, four (6.9%) F, one (1.7%) C, and
      14 (24.1%) BF recombinants. Four different BF recombination patterns were
      detected. Twelve (20.7%) samples shared the same breakpoint within the reverse
      transcriptase (RT) sequence. Fifty-five (94.8%) isolates showed several
      resistance-associated mutations in the RT and the protease (PR) genes. Ten
      (17.2%) isolates presented mutations associated with a high level of resistance:
      nine (15.5%) to nucleoside RT inhibitors (NRTI), four (6.9%) to nonnucleoside RT
      inhibitors (NNRTI), and three (5.2%) to PR inhibitors (PIs). Subtype B-infected
      patients had, on average, 0.5 high-level DRAM per sequence while no mutations
      were observed in BF recombinants, although the two groups were under ARV for a
      similar period of time. Our data indicate the predominance of the subtype B,
      followed by BF recombinants in this population, and the dissemination of a
      recombinant strain in Bahia, which could be related to adaptive advantages of
      these variants over the predominant subtype B.

PMID- 21087198
TI  - Presence of drug resistance mutations among drug-naive patients in Morocco.
AB  - The aim of the present study was to determine viral subtypes and resistance
      mutations to antiretroviral treatment (ART) in HIV-1-infected treatment-naive
      patients from Rabat, Morocco during the period 2005-2009. The protease and
      reverse transcriptase (RT) genes were sequenced, the phylogenetic trees were
      inferred, and the resistance-associated mutations to NRTIs, NNRTIs, and PIs were
      recorded according to the international list of surveillance drug resistance
      mutations (SDRMs). The viral subtypes were subtype B (74%), CRF02_AG (15%), A1
      (6%), C (2%), F1 (1%), CRF09 (1%), and CRF25_cpx (1%). The presence of DRMs was
      found in four (5.06%) of 91 patients; resistance mutations to NRTIs were M184V
      and T215I/S revertant mutations; resistance to NNRTIs was associated with K103N
      and resistance to PIs with V82A. These findings have relevant implications for
      the local molecular mapping of HIV-1 and future ART surveillance studies in the
      region.

PMID- 21087200
TI  - T-type calcium channels inhibitors: a patent review.
AB  - IMPORTANCE OF THE FIELD: T-type calcium channels are transmembrane proteins that
      regulate calcium entry in the cell in a voltage-dependent manner. Intracellular
      calcium levels are the key to many physiological processes, ranging from neuron
      firing to cardiac pacemaking. Inhibition of T-type calcium channels is heralded
      as a potential treatment to peripheral and CNS disorders, including hypertension,
      heart failure, sleep, epilepsy, drug addiction and neuropathic pain. AREAS
      COVERED IN THIS REVIEW: A comprehensive summary of patent literature disclosing T
      type calcium channels inhibitors is provided. WHAT THE READER WILL GAIN: In all,
      46 patent applications including 15 chemical structure classes are reviewed.
      Available in vitro, in vivo and clinical results are also discussed. TAKE HOME
      MESSAGE: Several selective T-type calcium channels inhibitors with demonstrated
      in vitro and in vivo effects, including one Phase I clinical candidate, are now
      available. While future clinical results will be paramount to assess target
      validity in patients, these novel inhibitors represent excellent tools to further
      investigate the role of T-type channels in pathophysiological conditions.

PMID- 21087199
TI  - Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells
      in self-gelling alginate discs reveals novel chondrogenic signature gene
      clusters.
AB  - We have used a disc-shaped self-gelling alginate hydrogel as a scaffold for in
      vitro chondrogenic differentiation of human bone marrow-derived mesenchymal stem
      cells. The comparison of monolayer cells and alginate embedded cells with or
      without differentiation medium allowed us to perform a detailed kinetic study of
      the expression of a range of genes and proteins known to be involved in
      chondrogenesis, using real-time polymerase chain reaction, fluorescence
      immunohistochemistry, and glycosaminoglycan measurement in the supernatant. mRNA
      encoding type II collagen (COL2), COL10, aggrecan, and SOX5, 6, and 9 were
      greatly elevated already at day 7, whereas COL1 and versican mRNA were gradually
      reduced. COL2 and aggrecan were dispersed throughout the extracellular matrix at
      day 21, whereas COL10 distribution was mainly intra/pericellular. COL1 seemed to
      be produced by only some of the cells. SOX proteins were predominantly localized
      in the nuclei. Then, using microarray analysis, we identified a signature cluster
      of extracellular matrix and transcription factor genes upregulated during
      chondrogenesis similar to COL2A1, and clusters of genes involved in immune
      responses, blood vessel development, and cell adhesion downregulated similar to
      the chemokine CXCL12. Analysis of the signature chondrogenic clusters, including
      novel potential marker genes identified here, may provide a better understanding
      of how the stem cell fate could be directed to produce perfect hyaline cartilage
      implants.

PMID- 21087201
TI  - Traumatic brain injuries.

PMID- 21087202
TI  - Endoscopic third ventriculostomy in adults: a technique for dealing with the
      neural (opaque) floor.
AB  - OBJECT: An opaque (neural) floor of the third ventricle is considered an obstacle
      to safe penetration of the floor of the third ventricle in endoscopic third
      ventriculostomy (ETV). The direct technique of endoscopic coring ("cookie cut")
      of the opaque (neural) floor of the third ventricle is described in 41 cases
      among a total of 101 consecutive adult ETVs. METHODS: A 0 degrees  endoscope in a
      4.6-mm irrigating sheath was used to press and core ("cookie cut") a section of
      the tuber cinereum, thereby exposing the underlying membranes and vasculature.
      Thereafter, the endoscopic apparatus was used to penetrate the membrane into the
      prepontine space. RESULTS: Among 101 consecutive ETVs performed in adults, there
      were 41 instances of an opaque floor in which the coring technique was used. The
      basilar artery (BA) complex was in the intended path of penetration in 13 cases.
      There were no perioperative deaths or vascular injuries. No cases were aborted
      because of the opaque floor or the configuration of the BA complex. The clinical
      success rate in the opaque floor group was 80% (33 of 41 patients). CONCLUSIONS:
      An opaque (neural) floor is frequently seen in adults during ETV. Removing the
      floor by the core ("cookie cut") method is a safe means of revealing the
      underlying BA complex and membranous structures prior to penetration into the
      prepontine cistern. On occasion, the BA complex may be in the path of
      penetration, and one can maneuver the endoscope to displace the vasculature to
      successfully accomplish the ETV.

PMID- 21087203
TI  - Comparison of mannitol and hypertonic saline in the treatment of severe brain
      injuries.
AB  - OBJECT: The purpose of this study was to compare the effects of mannitol and
      hypertonic saline in doses of similar osmotic burden for the treatment of
      intracranial hypertension in patients with severe traumatic brain injury.
      METHODS: The authors used an alternating treatment protocol to compare the effect
      of hypertonic saline with that of mannitol given for episodes of increased
      intracranial pressure in patients treated for severe head injury at their
      hospital during 2006-2008. Standard guidelines for the management of severe
      traumatic brain injury were followed. Elevated intracranial pressure (ICP) was
      treated either with mannitol or hypertonic saline. Doses of similar osmotic
      burden (mannitol 20%, 2 ml/kg, infused over 20 minutes, or saline 15%, 0.42
      ml/kg, administered as a bolus via a central venous catheter) were given
      alternately to the individual patient with severe brain injury during episodes of
      increased pressure. The dependent variables were the extent and duration of
      reduction of increased ICP. The choice of agent for treatment of the initial
      hypertensive event was determined on a randomized basis; treatment was alternated
      for every subsequent event in each individual patient. Reduction of ICP and
      duration of action were recorded after each event. Results obtained after
      mannitol administration were statistically compared with those obtained after
      hypertonic saline administration. RESULTS: Data pertaining to 199 hypertensive
      events in 29 patients were collected. The mean decrease in ICP obtained with
      mannitol was 7.96 mm Hg and that obtained with hypertonic saline was 8.43 mm Hg
      (p = 0.586, equal variances assumed). The mean duration of effect was 3 hours 33
      minutes for mannitol and 4 hours 17 minutes for hypertonic saline (p = 0.40,
      equal variances assumed). CONCLUSIONS: No difference between the 2 medications
      could be found with respect to the extent of reduction of ICP or duration of
      action.

PMID- 21087204
TI  - Scalable production of cardiomyocytes derived from c-Myc free induced pluripotent
      stem cells.
AB  - Cardiomyocytes derived from induced pluripotent stem (iPS) cells hold great
      promise for basic and translational cardiovascular research. For the successful
      implementation of this unique technology, however, it is essential to establish
      efficient, reproducible, and safe strategies to produce cardiomyocytes in a
      scalable manner. The aim of the current study was to establish scalable
      bioprocess that allows direct embryoid bodies formation for the differentiation
      of murine iPS cells (generated without the oncogene c-Myc) into cardiomyocytes.
      The cardiomyocytes' structural, molecular, and functional properties were then
      compared to ones derived by the well-established static culture system. Similar
      gene expression patterns were observed in both differentiation systems with the
      sequential expression of mesoderm markers, cardiac transcription factors, and
      cardiomyocyte structural genes. Cells in the contracting embryoid bodies were
      stained positively for cardiac troponin-I, sarcomeric alpha-actinin, cardiac
      troponin-T, and connexin-43. Electrophysiological measurements using
      multielectrode array recordings demonstrated that the bioreactor-derived
      cardiomyocytes were functionally similar to static derived cardiomyocytes and
      responded appropriately to different drugs, including adrenergic and muscarinic
      agonists (isoproterenol and carbamylcholine, respectively) and the gap junction
      uncoupler heptanol. Our study describes, for the first time, a strategy for
      scalable differentiation of c-Myc-free iPS cells into cardiomyocytes with the
      appropriate molecular, structural, and functional properties. The result of this
      study should have important implications for several cardiovascular research
      areas and specifically for the emerging field of regenerative medicine.

PMID- 21087205
TI  - Effects of non-steroidal anti-inflammatory drugs on proliferation,
      differentiation and migration in equine mesenchymal stem cells.
AB  - In equine medicine, stem cell therapies for orthopaedic diseases are routinely
      accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs).
      Thus, it has to be analysed how NSAIDs actually affect the growth and
      differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to
      predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and
      flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated
      regarding cell viability and proliferation. Additionally, the multilineage
      differentiation capacity and cell migration was analysed. NSAIDs at lower
      concentrations (0.1-1 MUM for celecoxib and meloxicam and 10-50 MUM for flunixin)
      exert a positive effect on cell proliferation and migration, while at higher
      concentrations (10-200 MUM for celecoxib and meloxicam and 100-1000 MUM for
      flunixin and phenylbutazone), there is rather a negative influence. While there
      is hardly any influence on the adipogenic as well as on the chondrogenic MSC
      differentiation, the osteogenic differentiation potential, as demonstrated with
      the von Kossa staining, is significantly disturbed. Thus, it can be concluded
      that the effects of NSAIDs on MSCs are largely dependent on the concentrations
      used. Additionally, for some differentiation lineages, also the choice of NSAID
      is critical.

PMID- 21087206
TI  - L-arginine promotes DNA repair in cultured bronchial epithelial cells exposed to
      ozone: involvement of the ATM pathway.
AB  - Ozone may lead to DNA breaks in airway epithelial cells. p-ATM (phosphorylated
      ataxia telangiectasia mutated) plays a pivotal role in DNA repair. Derivatives of
      NO (nitric oxide) are regulators of the phosphorylation, and NO is increased
      under oxidative stress. The present study was aimed to study the effect of NO
      donor L-arg (L-arginine) on DNA damage repair in human bronchial epithelial cells
      exposed to ozone and the potential mechanisms involved. HBECs (human bronchial
      epithelial cells) were cultured with or without ozone (1.5 ppm, 30 min), DNA
      breaks were measured with a comet assay and agarose gel electrophoresis, cell
      cycling was determined by flow cytometry and p-ATM was measured by
      immunofluorescence and Western blot. Data were analysed by ANOVA (analysis of
      variance). P<0.05 was considered as significant. Ozone induced marked DNA breaks,
      G1-phase arrest and increased expression of p-ATM in HBECs, while wortmannin
      reduced the levels of p-ATM induced by ozone; the NO donor, L-arg, minimized the
      effects of ozone-induced DNA breaks and increased the level of p-ATM, while the
      NO synthase inhibitor, L-NMMA [N(G)-minomethyl-L-arginine], restrained those
      effects of L-arg. The effect of L-arg on DNA repair is NO-mediated, and p-ATM is
      implicated in the processes of DNA repair.

PMID- 21087207
TI  - Analysis of apoptosis and DNA damage in bovine cumulus cells after exposure in
      vitro to different zinc concentrations.
AB  - The purpose of this study was to investigate the effect of Zn (zinc)
      concentration on CCs (cumulus cells) during in vitro maturation. For this
      purpose, DNA integrity of CCs by addition of different Zn concentrations [0
      (control); 0.7 MUg/ml (Zn1); 1.1 MUg/ml (Zn2) and 1.5 MUg/ml (Zn3)] to the
      culture medium was evaluated by comet assay. In addition, early apoptosis was
      analysed by annexin staining assay. CCs treated with Zn showed a significant
      decrease in the DNA damage in a dose-dependent manner. Comet assay analysed for
      TM (tail moment) was significantly higher in cells cultured without Zn (control,
      P<0.01) with respect to cells treated with Zn (control: 5.24+/-16.05; Zn1: 1.13+/
      5.31; Zn2: 0.10+/-0.36; Zn3: 0.017+/-0.06). All treatments were statistically
      different from the control (P = 0.014 for Zn1; P<0.01 for Zn2 and Zn3). The
      frequency of apoptotic cells was higher in the control group (control: 0.142+/
      0.07; Zn1: 0.109+/-0.0328; Zn2:0.102+/-0.013; Zn3: 0.0577+/-0.019). Statistical
      differences were found between control and Zn1 (P = 0.0308), control and Zn2 (P =
      0.0077), control and Zn3 (P<0.0001), Zn1 and Zn3 (P<0.001) and Zn2 and Zn3 (P =
      0.0004). No differences were found between Zn1 and Zn2. In conclusion, low Zn
      concentrations increase DNA damage and apoptosis in CCs cultured in vitro.
      However, adequate Zn concentrations 'protect' the integrity of DNA molecule and
      diminish the percentage of apoptotic CC.

PMID- 21087208
TI  - Divergence in enzyme regulation between Caenorhabditis elegans and human tyrosine
      hydroxylase, the key enzyme in the synthesis of dopamine.
AB  - TH (tyrosine hydroxylase) is the rate-limiting enzyme in the synthesis of
      catecholamines. The cat-2 gene of the nematode Caenorhabditis elegans is
      expressed in mechanosensory dopaminergic neurons and has been proposed to encode
      a putative TH. In the present paper, we report the cloning of C. elegans full
      length cat-2 cDNA and a detailed biochemical characterization of the encoded CAT
      2 protein. Similar to other THs, C. elegans CAT-2 is composed of an N-terminal
      regulatory domain followed by a catalytic domain and a C-terminal oligomerization
      domain and shows high substrate specificity for L-tyrosine. Like hTH (human TH),
      CAT-2 is tetrameric and is phosphorylated at Ser35 (equivalent to Ser40 in hTH)
      by PKA (cAMP-dependent protein kinase). However, CAT-2 is devoid of
      characteristic regulatory mechanisms present in hTH, such as negative co
      operativity for the cofactor, substrate inhibition or feedback inhibition exerted
      by catecholamines, end-products of the pathway. Thus TH activity in C. elegans
      displays a weaker regulation in comparison with the human orthologue, resembling
      a constitutively active enzyme. Overall, our data suggest that the intricate
      regulation characteristic of mammalian TH might have evolved from more simple
      models to adjust to the increasing complexity of the higher eukaryotes
      neuroendocrine systems.

PMID- 21087209
TI  - Hunting for fibrosis progression genes in hepatitis C patients.
AB  - HCV (hepatitis C virus) represents one of the major health problems worldwide, as
      almost 170 million people are infected and most of these develop a chronic
      disease, often with the progression to cirrhosis and its complications. In the
      present issue of Clinical Science, Iwata and co-workers report an association
      between a variant of a gene regulating bile acid levels, ABCB11 1331T>C (where
      ABCB11 encodes ATP-binding cassette, subfamily B, member 11), and the progression
      to cirrhosis in patients with HCV, but not in fatty liver patients. They
      correlate this genetic variant with increased serum bile acid levels as a marker
      of cholestasis. These findings have important implications for researchers
      working to dissect the molecular mechanisms underlying liver fibrogenesis and
      disease progression; however, the implications for clinical hepatologists are
      less immediate.

PMID- 21087210
TI  - Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1.
AB  - PDK1 (3-phosphoinositide-dependent protein kinase 1) activates a group of protein
      kinases belonging to the AGC [PKA (protein kinase A)/PKG (protein kinase G)/PKC
      (protein kinase C)]-kinase family that play important roles in mediating diverse
      biological processes. Many cancer-driving mutations induce activation of PDK1
      targets including Akt, S6K (p70 ribosomal S6 kinase) and SGK (serum- and
      glucocorticoid-induced protein kinase). In the present paper, we describe the
      small molecule GSK2334470, which inhibits PDK1 with an IC50 of ~10 nM, but does
      not suppress the activity of 93 other protein kinases including 13 AGC-kinases
      most related to PDK1 at 500-fold higher concentrations. Addition of GSK2334470 to
      HEK (human embryonic kidney)-293, U87 or MEF (mouse embryonic fibroblast) cells
      ablated T-loop residue phosphorylation and activation of SGK isoforms and S6K1
      induced by serum or IGF1 (insulin-like growth factor 1). GSK2334470 also
      inhibited T-loop phosphorylation and activation of Akt, but was more efficient at
      inhibiting Akt in response to stimuli such as serum that activated the PI3K
      (phosphoinositide 3-kinase) pathway weakly. GSK2334470 inhibited activation of an
      Akt1 mutant lacking the PH domain (pleckstrin homology domain) more potently than
      full-length Akt1, suggesting that GSK2334470 is more effective at inhibiting PDK1
      substrates that are activated in the cytosol rather than at the plasma membrane.
      Consistent with this, GSK2334470 inhibited Akt activation in knock-in embryonic
      stem cells expressing a mutant of PDK1 that is unable to interact with
      phosphoinositides more potently than in wild-type cells. GSK2334470 also
      suppressed T-loop phosphorylation and activation of RSK2 (p90 ribosomal S6 kinase
      2), another PDK1 target activated by the ERK (extracellular-signal-regulated
      kinase) pathway. However, prolonged treatment of cells with inhibitor was
      required to observe inhibition of RSK2, indicating that PDK1 substrates possess
      distinct T-loop dephosphorylation kinetics. Our data define how PDK1 inhibitors
      affect AGC signalling pathways and suggest that GSK2334470 will be a useful tool
      for delineating the roles of PDK1 in biological processes.

PMID- 21087211
TI  - ERK/p90(RSK)/14-3-3 signalling has an impact on expression of PEA3 Ets
      transcription factors via the transcriptional repressor capicua.
AB  - Compounds that inhibit signalling upstream of ERK (extracellular-signal-regulated
      kinase) are promising anticancer therapies, motivating research to define how
      this pathway promotes cancers. In the present study, we show that human capicua
      represses mRNA expression for PEA3 (polyoma enhancer activator 3) Ets
      transcription factors ETV1, ETV4 and ETV5 (ETV is Ets translocation variant), and
      this repression is relieved by multisite controls of capicua by ERK, p90(RSK)
      (p90 ribosomal S6 kinase) and 14-3-3 proteins. Specifically, 14-3-3 binds to
      p90(RSK)-phosphorylated Ser173 of capicua thereby modulating DNA binding to its
      HMG (high-mobility group) box, whereas ERK phosphorylations prevent binding of a
      C-terminal NLS (nuclear localization sequence) to importin alpha4 (KPNA3). ETV1,
      ETV4 and ETV5 mRNA levels in melanoma cells are elevated by siRNA (small
      interfering RNA) knockdown of capicua, and decreased by inhibiting ERK and/or
      expressing a form of capicua that cannot bind to 14-3-3 proteins. Capicua
      knockdown also enhances cell migration. The findings of the present study give
      further mechanistic insights into why ETV1 is highly expressed in certain
      cancers, indicate that loss of capicua can desensitize cells to the effects of
      ERK pathway inhibitors, and highlight interconnections among growth factor
      signalling, spinocerebellar ataxias and cancers.

PMID- 21087212
TI  - Renin, (pro)renin and receptor: an update.
AB  - PRR [(pro)renin receptor] was named after its biological characteristics, namely
      the binding of renin and of its inactive precursor prorenin, that triggers
      intracellular signalling involving ERK (extracellular-signal-regulated kinase)
      1/2. However the gene encoding for PRR is named ATP6ap2 (ATPase 6 accessory
      protein 2) because PRR was initially found as a truncated form co-purifying with
      V-ATPase (vacuolar H+-ATPase). There are now data showing that this interaction
      is not only physical, but also functional in the kidney and the heart. However,
      the newest and most fascinating development of PRR is its involvement in both the
      canonical Wnt/beta-catenin and non-canonical Wnt/PCP (planar cell polarity)
      pathways, which are essential for adult and embryonic stem cell biology,
      embryonic development and disease, including cancer. In the Wnt/beta-catenin
      pathway, it has been shown that PRR acts as an adaptor between the Wnt receptor
      LRP5/6 (low-density lipoprotein receptor-related protein 5/6) and Fz (frizzled)
      and that the proton gradient generated by the V-ATPase in endosomes is necessary
      for LRP5/6 phosphorylation and beta-catenin activation. In the Wnt/PCP pathway,
      PRR binds to Fz and controls its asymetrical subcellular distribution and
      therefore the polarization of the cells in a plane of a tissue. These essential
      cellular functions of PRR are independent of renin and open new avenues on the
      pathophysiological role of PRR. The present review will summarize our knowledge
      of (pro)renin-dependent functions of PRR and will discuss the newly recognized
      functions of PRR related to the V-ATPase and to Wnt signalling.

PMID- 21087213
TI  - Co-transfection and tandem transfection of HEK293A cells for overexpression and
      RNAi experiments.
AB  - pIRES2-EGFP was employed and a non-target shRNA expressing plasmid was
      constructed to simulate overexpression and RNAi (RNA interference) experiments.
      Transfection of pIRES2-EGFP into HEK293A cells by cationic lipids VigoFect
      demonstrated that transfection efficiency increased in a dose-dependent manner
      with amount of DNA plasmid used, and optimal transfection time and cell density
      should be identified to reach a compromise of higher transfection efficiency and
      lower toxicity. Co-transfection experiments indicated that the two co-transfected
      plasmids were equivalently delivered into the same cells, and the co-transfection
      efficiency was rarely affected by cell density and proportion of the two
      plasmids. However, plasmid-receipted cells seemed indisposed to accept plasmid
      again during the second transfection, and very low co-transfection efficiency was
      observed in tandem transfection.

PMID- 21087214
TI  - Staphylococci and staphylococcal superantigens in asthma and rhinitis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There is a need for new treatment options of allergic respiratory
      diseases based on a better knowledge of their pathogenesis. An association
      between bacterial products and allergic airway diseases has been suggested by the
      results of human and animal studies that describe a link between Staphylococcus
      aureus enterotoxins and atopic diseases. The aim of the systematic review is to
      assess the evidence for a role of Staphylococcus aureus enterotoxins, as an
      environmental risk factor, for the development and/or the severity of asthma and
      allergic rhinitis. METHODS: We performed a systematic review of controlled
      clinical studies in adults and/or children affected by asthma/early wheeze and/or
      allergic rhinitis. To be eligible, studies had to use reproducible methods to
      provide evidence of exposure to S. aureus, clinical outcome and disease severity.
      RESULTS: Ten studies, published between 2000 and 2007, fulfilled all eligibility
      criteria. Patients with asthma or allergic rhinitis showed an increased
      prevalence of positivity for measures of exposure to S. aureus in nine studies:
      differences were statistically significant (P < 0.05) in seven studies. In a meta
      analysis of study results, patients with asthma were more likely than controls to
      have serum-specific IgE to Staphylococcus aureus enterotoxins (OR = 3.3, 95% CI:
      1.6-7.1, P = 0.002); similarly, patients with allergic rhinitis were more likely
      than controls to test positive for local or systemic exposure to Staphylococcus
      aureus and/or or its enterotoxins (OR = 2.4, 95% CI: 1.3-4.7, P = 0.008).
      CONCLUSIONS: A potential role of S. aureus superantigens in allergic respiratory
      diseases is supported by results of this meta-analysis of clinical studies.

PMID- 21087215
TI  - Viruses and bacteria in acute asthma exacerbations--a GA2 LEN-DARE systematic
      review.
AB  - A major part of the burden of asthma is caused by acute exacerbations.
      Exacerbations have been strongly and consistently associated with respiratory
      infections. Respiratory viruses and bacteria are therefore possible treatment
      targets. To have a reasonable estimate of the burden of disease induced by such
      infectious agents on asthmatic patients, it is necessary to understand their
      nature and be able to identify them in clinical samples by employing accurate and
      sensitive methodologies. This systematic review summarizes current knowledge and
      developments in infection epidemiology of acute asthma in children and adults,
      describing the known impact for each individual agent and highlighting knowledge
      gaps. Among infectious agents, human rhinoviruses are the most prevalent in
      regard to asthma exacerbations. The newly identified type-C rhinoviruses may
      prove to be particularly relevant. Respiratory syncytial virus and
      metapneumovirus are important in infants, while influenza viruses seem to induce
      severe exacerbations mostly in adults. Other agents are relatively less or not
      clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved
      more with asthma persistence rather than with disease exacerbations. Recent data
      suggest that common bacteria may also be involved, but this should be confirmed.
      Although current information is considerable, improvements in detection
      methodologies, as well as the wide variation in respect to location, time and
      populations, underline the need for additional studies that should also take into
      account interacting factors.

PMID- 21087216
TI  - Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells
      predominate the microenvironment within distinct oral mucosal sites.
AB  - BACKGROUND: Most local oral vaccine strategies use the sublingual region for drug
      application. Only little is known about the cytokine micromilieu, the nature of T
      cell subtypes and expression of target structures for adjuvants at different oral
      mucosal regions (OMR). However, targeting the optimal OMR might ensure highest
      efficiency of drug uptake and lowest risk for adverse effects. METHODS:
      Expression of TGF-beta1, IL10 as well as Th1, Th2 and Th17 cytokines and
      transcription factors was investigated at different OMR and skin by quantitative
      real-time PCR, immunohistochemistry or flow cytometry. RESULTS: Highest number of
      T cells was located in vestibular/buccal region (VBR). In contrast to skin (SK),
      OMR T cells produced TGF-beta1, IL-10, IFN-gamma and IL-17. Significantly higher
      TGF-beta1 mRNA expression in the VBR compared with the sublingual region (SLR)
      and skin could be detected, while equal transcripts of IL-10 and regulatory T
      cell-associated transcription factor FoxP3 could be demonstrated. Expression of
      Th17-associated IL-17A, IL-17F, IL-22 and IL-26 mRNA could be demonstrated in VBR
      and SLR but not in SK. Interestingly, compared to SK, significantly higher
      expression of TGF-beta1 and IFN-gamma could be detected in OMR. Moreover,
      expression of toll-like receptor (TLR) 2 and TLR4 was highest in VBR with
      significant expression on dendritic cells in OMR. CONCLUSION: From this data, we
      conclude that (i) VBR and SLR represent a protolerogenic micromilieu, (ii) both
      regions form a Th1 cytokine-predominated microenvironment, but also express mRNA
      for Th17 cytokines and (iii) TLRs detectable in VBR and SLR might serve as a
      target structures for adjuvants.

PMID- 21087217
TI  - Atopy and current intestinal parasite infection: a systematic review and meta
      analysis.
AB  - BACKGROUND: The rate of increase in prevalence of allergic disease in some
      countries implies environmental exposures may be important etiological factors.
      Our aim was to undertake a systematic review and meta-analysis of epidemiological
      studies to quantify the association between current intestinal parasite infection
      and the presence of atopy and to determine whether this relation is species
      specific. METHODS: We searched MEDLINE, EMBASE, LILIACS and CAB Abstracts (to
      March 2009); reviews; and reference lists from publications. No language
      restrictions were applied. We included studies that measured current parasite
      infection using direct fecal microscopy and defined atopy as allergen skin
      sensitization or presence of specific IgE. We estimated pooled odds ratios (OR)
      and 95% confidence intervals (95% CI) using data extracted from published papers
      using random-effects model. RESULTS: Twenty-one studies met our inclusion
      criteria. Current parasite infection was associated with a reduced risk of
      allergen skin sensitization OR 0.69 (95% CI 0.60-0.79; P < 0.01). When we
      restricted our analyses to current geohelminth infection, the size of effect
      remained similar OR 0.68 (95% CI 0.60-0.76; P < 0.01). In species-specific
      analysis, a consistent protective effect was found for infection with Ascaris
      lumbricoides, Tricuris trichuria, hookworm and Schistosomiasis. There were
      insufficient data to pool results for atopy defined by the presence of specific
      IgE. CONCLUSION: Intestinal parasite infection appears to protect against
      allergic sensitization. Work should continue to identify the mechanisms of this
      effect and means of harnessing these to reduce the global burden of allergic
      disease.

PMID- 21087218
TI  - Familiarity breeds progeny: sociality increases reproductive success in adult
      male ring-tailed coatis (Nasua nasua).
AB  - The ring-tailed coati (Nasua nasua) is the only coati species in which social
      groups contain an adult male year round, although most males live solitarily. We
      compared reproductive success of group living and solitary adult male coatis to
      determine the degree to which sociality affects reproductive success. Coati
      mating is highly seasonal and groups of female coatis come into oestrus during
      the same 1-2 week period. During the mating season, solitary adult males followed
      groups and fought with the group living male. This aggression was presumably to
      gain access to receptive females. We expected that high reproductive synchrony
      would make it difficult or impossible for the one group living male to monopolize
      and defend the group of oestrous females. However, we found that group living
      males sired between 67-91% of the offspring in their groups. This reproductive
      monopolization is much higher than other species of mammals with comparably short
      mating seasons. Clearly, living in a group greatly enhanced a male's reproductive
      success. At the same time, at least 50% of coati litters contained offspring
      sired by extra-group males (usually only one offspring per litter); thus,
      resident males could not prevent extra-group matings. The resident male's
      reproductive advantage may reflect female preference for a resident male strong
      enough to fend off competing males.

PMID- 21087219
TI  - Depressive symptoms, chronic diseases, and physical disabilities as predictors of
      cognitive functioning trajectories in older Americans.
AB  - OBJECTIVES: To determine the concurrent influence of depressive symptoms, medical
      conditions, and disabilities in activities of daily living (ADLs) on rates of
      decline in cognitive function of older Americans. DESIGN: Prospective cohort.
      SETTING: National population based. PARTICIPANTS: A national sample of 6,476
      adults born before 1924. MEASUREMENTS: Differences in cognitive function
      trajectories were determined according to prevalence and incidence of depressive
      symptoms, chronic diseases, and ADL disabilities. Cognitive performance was
      tested five times between 1993 and 2002 using a multifaceted inventory examined
      as a global measure (range 0-35, standard deviation (SD) 6.0) and word recall
      (range 0-20, SD 3.8) analyzed separately. RESULTS: Baseline prevalence of
      depressive symptoms, stroke, and ADL limitations were independently and strongly
      associated with lower baseline cognition scores but did not predict future
      cognitive decline. Each incident depressive symptom was independently associated
      with a 0.06-point lower (95% confidence interval (CI)=0.02-0.10) recall score,
      incident stroke with a 0.59-point lower total score (95% CI=0.20-0.98), each new
      basic ADL limitation with a 0.07-point lower recall score (95% CI=0.01-0.14) and
      a 0.16-point lower total score (95% CI=0.07-0.25), and each incident instrumental
      ADL limitation with a 0.20-point lower recall score (95% CI=0.10-0.30) and a 0.52
      point lower total score (95% CI=0.37-0.67). CONCLUSION: Prevalent and incident
      depressive symptoms, stroke, and ADL disabilities contribute independently to
      poorer cognitive functioning in older Americans but do not appear to influence
      rates of future cognitive decline. Prevention, early identification, and
      aggressive treatment of these conditions may ameliorate the burdens of cognitive
      impairment.

PMID- 21087220
TI  - The effect of homebound status on older persons.
AB  - OBJECTIVES: To examine the effect of homebound status of older persons in Israel
      on mortality, mental health and function, future homebound status, and
      institutionalization. DESIGN: Cross-sectional and longitudinal analysis using
      existing data sets of a national survey. SETTING: A national survey.
      PARTICIPANTS: The analyzed sample was drawn from a representative cohort of 1,191
      older persons in Israel (mean age 83.1+/-5.3) in the first wave of the Cross
      Sectional and Longitudinal Aging Study and 621 participants in the second wave of
      the study. MEASUREMENTS: Homebound status, health, function, environment, mental
      health, distal events, mortality, activities daily living (ADLs), instrumental
      activities of daily living (IADLs), Orientation-Memory-Concentration Test, and
      Center for Epidemiologic Studies Depression Scale. Mortality data were recorded
      from the Israeli National Population Registry. RESULTS: Homebound participants
      had a significantly higher risk of mortality than their non-homebound
      counterparts, even after controlling for background variables, health, and
      function (risk ratio=1.33, 95% confidence interval=1.08-1.63). In cross-sectional
      analysis, homebound status was related to depressed affect even after controlling
      for demographics, health, and function. In longitudinal analysis, homebound
      status predicted future depressed affect and ADL and IADL difficulties when
      controlling for demographics and health, but only IADL prediction was
      statistically significant when baseline levels of the outcome variable were
      entered into the regression. CONCLUSION: The results highlight the detrimental
      effects of homebound status, underscoring the importance of preventing this
      state, of interventions to assist those who are homebound, and of future research
      to examine the efficacy and coverage of services to this population.

PMID- 21087221
TI  - Cognition moderates the relationship between facility characteristics, personal
      impairments, and nursing home residents' activities of daily living.
AB  - OBJECTIVES: To determine whether cognition moderates the association between
      facility-level characteristics and individual-level impairments and activity of
      daily living (ADL) dependency. DESIGN: Longitudinal cohort study. SETTINGS:
      Nursing homes (NHs) in Minnesota. PARTICIPANTS: Four thousand nine hundred forty
      two NH residents admitted to 377 Minnesota NHs during 2004 were followed for 4 to
      8 months. MEASUREMENTS: According to the Minimum Data Set (MDS) Cognition Scale
      3,132 residents had high cognitive function, and 1,810 had low cognitive
      function. Total ADL score and scores on three ADL tasks at follow-up were used as
      outcome variables. MDS-derived impairment measures at admission of pain,
      depression, incontinence, balance dysfunction, and fall history were used to
      predict ADL changes. Fifteen resident-level and eight facility-level control
      variables were included in all four ADL models. RESULTS: Effects of NHs and
      impairments on ADLs tended to be weaker for residents with low cognitive
      function. Bladder incontinence significantly predicted more dependence in total
      ADLs, toileting, and personal hygiene in both cognitive groups. Balance
      dysfunction significantly predicted worse total ADLs, toileting, and personal
      hygiene in the high-cognition group but only worse toileting function in the low
      cognition group. In neither subgroup did any impairment predict worse eating
      function. Cognition did not modify the relationships between pain, depression,
      and recent falls and ADLs. CONCLUSION: Current NH environments and care processes
      may be inadequate to facilitate ADL changes for residents with severe cognitive
      impairment. More innovative structural designs, higher staffing levels, and
      better care processes may be indicated.

PMID- 21087222
TI  - Individualized nutritional intervention during and after hospitalization: the
      nutrition intervention study clinical trial.
AB  - OBJECTIVES: To test the hypothesis that individualized nutritional treatment
      during and after discharge from acute hospitalization will reduce mortality and
      improve nutritional outcomes. DESIGN: Randomized, controlled trial. SETTING:
      Internal medicine departments. PARTICIPANTS: Two hundred fifty-nine hospitalized
      adults aged 65 and older at nutritional risk were recruited and randomized
      according to hospitalization ward into one intervention and two control groups
      during hospitalization. INTERVENTION: Group 1 (intervention group) received
      individualized nutritional treatment from a dietitian in the hospital and three
      home visits after discharge. Group 2 received one meeting with a dietitian in the
      hospital. Group 3 received standard care. Groups 2 and 3 were combined into a
      single group that served as the control group in the analysis. MEASUREMENTS:
      Mortality, health status, nutritional outcomes, blood tests, cognition,
      emotional, and functional parameters were assessed at baseline and after 6
      months. All participants were contacted monthly. RESULTS: The overall dropout
      rate was 25.8%. After 6 months, rise in Mini Nutritional Assessment score,
      adjusted for education and hospitalization ward, was significantly higher in the
      intervention group than in the control groups (3.01 +/- 2.65 vs 1.81 +/- 2.97, P
      =.004) mainly on the subjective assessment part (0.34 +/- 0.86 vs. -0.04 +/-
      0.87, P=.004). The only laboratory parameter for which a difference was observed
      between the groups was albumin; 9.7% of the intervention group had serum albumin
      levels of less than 3.5 g/dL, versus 22.9% of the control group (P =.03).
      Mortality was significantly lower in the intervention group (3.8%) than in the
      control group (11.6%, P =.046). CONCLUSION: Lower mortality and moderate
      improvement in nutritional status were found in patients receiving individualized
      nutritional treatment during and after acute hospitalization.

PMID- 21087223
TI  - Does nonresponse bias the results of retrospective surveys of end-of-life care?
AB  - OBJECTIVES: To evaluate the effect of nonresponse bias on reports of the quality
      of end-of-life care that older adults receive. DESIGN: Nationwide retrospective
      survey of end-of-life care. SETTING: Sixty-two Veterans Affairs Medical Centers.
      PARTICIPANTS: Patients were eligible if they died in a participating facility.
      One family member per patient was selected from medical records and invited to
      participate. MEASUREMENTS: The telephone survey included 14 items describing
      important aspects of the patient's care in the last month of life. Scores (0-100)
      reflect the percentage of items for which the family member reported that the
      patient received the best possible care, and a global item defined the proportion
      of families who said the patient received "excellent" care. To examine the effect
      of nonresponse bias, a model was created to predict the likelihood of response
      based on patient and family characteristics; then this model was used to apply
      weights that were equivalent to the inverse of the probability of response for
      that individual. RESULTS: Interviews were completed with family members of 3,897
      of 7,110 patients (55%). Once results were weighted to account for nonresponse
      bias, the change in mean individual scores was 2% of families reporting
      "excellent" care. Of the 62 facilities in the sample, the scores of only 19
      facilities (31%) changed more than 1% in either direction, and only 10 (16%)
      changed more than 2%. CONCLUSION: Although nonresponse bias is a theoretical
      concern, it does not appear to have a significant effect on the facility-level
      results of this retrospective family survey.

PMID- 21087224
TI  - Correlates of alcohol-related discussions between older adults and their
      physicians.
AB  - OBJECTIVES: To identify predictors of alcohol-related patient-physician
      discussions. DESIGN: Cross-sectional study using baseline data from a randomized
      controlled trial. SETTING: Community-based group practice. PARTICIPANTS: Thirty
      one physicians in Project Senior Health and Alcohol Risk Education and 3,305 of
      their patients aged 60 and older who use alcohol and completed a survey that
      included the Comorbidity Alcohol Risk Evaluation Tool (CARET). MEASUREMENTS: At
      study baseline, older adults were asked whether alcohol-related discussions with
      a physician had occurred in the prior year. This outcome was modeled using
      logistic regression models with physician random effects. Predictor variables
      included patient-level variables such as demographics and seven CARET-defined
      risk factors, specifically a medical or psychiatric comorbidity that alcohol
      might worsen, a potentially alcohol-related symptom, use of a medication that may
      interact negatively with alcohol, excessive quantity or frequency of alcohol use,
      binge drinking, concern from others about drinking, and drinking and driving.
      Physician-level predictors (age, sex, years since graduation, specialty) were
      also included. RESULTS: The probability of reporting alcohol-related discussions
      declined with patient age (e.g., odds ratio (OR)=0.40 for patients aged >=80) and
      was significantly lower for Latinos (OR=0.38). Drinking and driving (OR=1.69) or
      concern from others (OR=6.04) were significantly associated with alcohol-related
      discussions; having comorbidities or using medications that may interact with
      alcohol were not. CONCLUSION: Although patient demographics, including age and
      ethnicity, are associated with the occurrence of alcohol-related discussions,
      clinical factors that may negatively interact with alcohol to increase risk are
      not. This suggests that physicians may not be attuned to the entire spectrum of
      alcohol-related risks for older adults.

PMID- 21087226
TI  - Alcohol use trajectories in two cohorts of U.S. women aged 50 to 65 at baseline.
AB  - OBJECTIVES: To examine drinking trajectories followed by two cohorts of older
      women over 8 to 10 years of follow-up. DESIGN: Longitudinal analyses of two
      nationally representative cohorts using semiparametric group-based models
      weighted and adjusted for baseline age. SETTING: Study data were obtained from
      detailed interviews conducted in the home or by telephone. PARTICIPANTS: One
      cohort included 5,231 women in the Health and Retirement Study (HRS) aged 50 to
      65 in 1996; the other included 1,658 women in the National Longitudinal Survey
      (NLS) aged 50 to 65 in 1995. MEASUREMENTS: Both cohorts reported any recent
      drinking and average number of drinks per drinking day using similar but not
      identical questions. HRS women completed six interviews (one every other year)
      from 1996 to 2006. NLS women completed five interviews from 1995 to 2003.
      RESULTS: All trajectory models yielded similar results. For HRS women, four
      trajectory groups were observed in the model based on drinks per day: increasing
      drinkers (4.9% of cohort), infrequent and nondrinkers (61.8%), consistent
      drinkers (25.9%), and decreasing drinkers (7.4%). Corresponding NLS values from
      the drinks per day model were 8.8%, 61.4%, 21.2%, and 8.6%, respectively. In
      2006, the average number of drinks per day for HRS women in the increasing
      drinker and consistent drinker trajectories was 1.31 and 1.59, respectively. In
      2003, these values for NLS women were 0.99 and 1.38, respectively. CONCLUSION:
      Most women do not markedly change their drinking behavior after age 50, but some
      increase their alcohol use substantially, whereas others continue to exceed
      current recommendations. These findings underscore the importance of periodically
      asking older women about their drinking to assess, advise, and assist those who
      may be at risk for developing alcohol-related problems.

PMID- 21087225
TI  - Burden in caregivers of older adults with advanced illness.
AB  - OBJECTIVES: To examine caregiver burden over time in caregivers of patients with
      advanced chronic disease. DESIGN: Observational cohort with interviews over 12
      months. SETTING: Community. PARTICIPANTS: Caregivers of 179 community-living
      persons aged 60 and older with advanced cancer, heart failure (HF), or chronic
      obstructive pulmonary disease (COPD). MEASUREMENTS: Caregiver burden was assessed
      using a short-form of the Zarit Burden Inventory to measure psychosocial
      distress. RESULTS: At baseline, the median caregiver burden was 5 (interquartile
      range (IQR) 1-11), which indicates that the caregiver endorsed having at least
      two of 10 distressing concerns at least some of the time. Only 10% reported no
      burden. Although scores increased modestly over time, the association between
      time and burden was not significant in longitudinal multivariable analysis. High
      burden was associated with caregiver need for more help with daily tasks (odds
      ratio (OR)=23.13, 95% confidence interval (CI)=5.94-90.06) and desire for greater
      communication with the patient (OR=2.53, 95% CI=1.16-5.53). The longitudinal
      multivariable analysis did not yield evidence of associations between burden and
      patient sociodemographic or health characteristics. CONCLUSION: Caregiver burden
      was common in caregivers of patients with cancer, HF, and COPD. High burden was
      associated with the caregiver's report of need for greater help with daily tasks
      but not with objective measures of the patient's need for assistance, such as
      symptoms or functional status, suggesting that burden may be a measure of the
      caregiver's ability to adapt to the caregiving role.

PMID- 21087227
TI  - Pragmatic approach to the clinical work-up of patients with putative allergic
      disease to metallic orthopaedic implants before and after surgery.
AB  - Allergic complications following insertion of metallic orthopaedic implants
      include allergic dermatitis reactions but also extracutaneous complications. As
      metal-allergic patients and/or surgeons may ask dermatologists and allergologists
      for advice prior to planned orthopaedic implant surgery, and as surgeons may
      refer patients with complications following total joint arthroplasty for
      diagnostic work-up, there is a continuous need for updated guidelines. This
      review presents published evidence for patch testing prior to surgery and
      proposes tentative diagnostic criteria which clinicians can rely on in the work
      up of patients with putative allergic complications following surgery. Few
      studies have investigated whether subjects with metal contact allergy have
      increased risk of developing complications following orthopaedic implant
      insertion. Metal allergy might in a minority increase the risk of complications
      caused by a delayed-type hypersensitivity reaction. At present, we do not know
      how to identify the subgroups of metal contact allergic patients with a
      potentially increased risk of complications following insertion of a metal
      implant. We recommend that clinicians should refrain from routine patch testing
      prior to surgery unless the patient has already had implant surgery with
      complications suspected to be allergic or has a history of clinical metal
      intolerance of sufficient magnitude to be of concern to the patient or a health
      provider. The clinical work-up of a patient suspected of having an allergic
      reaction to a metal implant should include patch testing and possibly in vitro
      testing. We propose diagnostic criteria for allergic dermatitis reactions as well
      as noneczematous complications caused by metal implants.

PMID- 21087228
TI  - Interleukin-18 is elevated in the horny layer in patients with atopic dermatitis
      and is associated with Staphylococcus aureus colonization.
AB  - BACKGROUND: An increase in interleukin (IL)-18 production from epidermal cells
      has been reported in an atopic dermatitis (AD) mouse model, and subsequent
      topical application of Staphylococcus aureus results in severe dermatitis.
      OBJECTIVES: To reveal the relationship between S. aureus colonization of skin
      lesions and keratinocyte IL-18 production, particularly in AD with relatively low
      serum IgE levels. We also aimed to establish a simple and noninvasive method of
      assaying IL-18 produced by epidermal keratinocytes to evaluate local skin
      inflammation and therapeutic effects in patients with AD. METHODS: IL-18 in the
      horny layer of the skin was collected via a tape-stripping method and measured in
      95 patients with AD and 40 healthy controls by enzyme-linked immunosorbent assay
      (ELISA). Clinical severity, blood data and S. aureus skin colonization were
      evaluated before and after treatment. RESULTS: IL-18 levels in the horny layer
      were significantly higher in the skin lesions of patients with AD than in healthy
      controls and correlated with SCORAD, levels of serum IL-18, IgE, lactate
      dehydrogenase, thymus and activation-regulated chemokine, blood eosinophils and
      transepidermal water loss. In the AD group with serum IgE < 1500 IU mL(-1) ,
      significantly higher IL-18 levels were observed in the horny layer of patients
      colonized with S. aureus compared with those who were not. CONCLUSIONS: Epidermal
      IL-18 production was associated with the severity of AD. Staphylococcus aureus
      colonization seems to contribute to this IL-18 production, especially in the AD
      group with relatively low IgE production. Tape stripping provides an easy and
      noninvasive method to assess epidermal IL-18 production by ELISA.

PMID- 21087229
TI  - Correlation between serum 25-hydroxyvitamin D levels and severity of atopic
      dermatitis in children.
AB  - BACKGROUND: Vitamin D deficiency could be associated with the prevalence of
      atopic dermatitis (AD). OBJECTIVES: We carried out a study to see whether
      deficient/insufficient levels of vitamin D correlate with the severity of atopic
      skin disease. METHODS: Using the SCORAD index, we evaluated the severity of
      disease in 37 children (17 girls and 20 boys) aged between 8 months and 12 years
      with AD, consecutively enrolled in the study. Serum levels of 25-hydroxyvitamin D
      [25(OH)D] were determined by a chemiluminescent method. Specific IgE (sIgE) to
      Staphylococcus aureus enterotoxins and sIgE to Malassezia furfur were assayed by
      the ImmunoCAP system. anova and the Pearson correlation test were used for
      statistical evaluation. RESULTS: We found severe, moderate and mild AD in nine
      (24%), 13 (35%) and 15 (41%) children, respectively. Mean +/- SD serum levels of
      25(OH)D were significantly higher (P < 0.05) in patients with mild disease (36.9
      +/- 15.7 ng mL(-1)) compared with those with moderate (27.5 +/- 8.3 ng mL(-1)) or
      severe AD (20.5 +/- 5.9 ng mL(-1)). The prevalence of patients with sIgE to
      microbial antigens increased in relation to vitamin D deficiency and AD severity.
      CONCLUSIONS: These data suggest that vitamin D deficiency may be related to the
      severity of AD and advocate the need for studies evaluating the use of vitamin D
      as a potential treatment in patients with this disease.

PMID- 21087230
TI  - Noninvasive cutaneous blood flow as a response predictor for visible light
      therapy on segmental vitiligo: a prospective pilot study.
AB  - BACKGROUND: Visible light is a treatment option for segmental vitiligo (SV), and
      visible light-induced repigmentation is associated with normalization of
      sympathetic dysfunction. Currently, it is difficult to predict individual
      patients' response to visible light therapy. OBJECTIVES: To test whether
      cutaneous blood flow can serve as a response predictor for visible light on
      treating SV. METHODS: Fourteen patients with SV were recruited in this
      prospective pilot study. Laser Doppler flowmetry was used to evaluate the
      cutaneous blood flow over SV lesions and contralateral normal skin. The
      pretreatment blood flow evaluation consisted of two stages: stage 1, following
      cold stress without prior visible light irradiation, and stage 2, following cold
      stress with prior visible light irradiation. Subsequently, the patients received
      regular visible light treatment for 3months, and a comparison of the pretreatment
      blood flow patterns between the visible light responding and nonresponding groups
      was carried out at the end of the study period. RESULTS: The SV lesions showed
      different blood flow profiles as compared with the contralateral normal skin. At
      the end of the 3-month study period, seven (50%) patients showed clinical
      repigmentation of >25%. The visible light responding group showed a more
      consistent occurrence of increased blood flow after stage 2 of the pretreatment
      evaluation while the nonresponding counterpart showed no significant changes.
      CONCLUSIONS: Normalization of sympathetic dysfunction may account for the
      efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with
      and without prior visible light irradiation on cold-stressed SV lesions may serve
      as a treatment response predictor.

PMID- 21087231
TI  - Whole-exome sequencing: a powerful technique for identifying novel genes of
      complex disorders.

PMID- 21087232
TI  - Magnetic resonance imaging of the fetus.
AB  - Fetal magnetic resonance imaging (MRI) has become established as part of clinical
      practice in many centres worldwide especially when visualization of the central
      nervous system pathology is required. In this review we summarize the recent
      literature and provide an overview of fetal development and the commonly
      encountered fetal pathologies visualized with MRI and illustrated with numerous
      MR images. We aim to convey the role of fetal MRI in clinical practice and its
      value as an additional investigation alongside ultrasound yet emphasize the need
      for caution when interpreting fetal MR images especially where experience is
      limited.

PMID- 21087233
TI  - Development and reliability of a classification system for gross motor function
      in children with metachromatic leucodystrophy.
AB  - AIM: Motor deterioration is a key feature of late infantile and juvenile
      metachromatic leucodystrophy (MLD). Assessment of the disease course implies the
      need for a standardized description of motor decline. The aim of this study was
      to establish a classification system for gross motor function in MLD and to
      assess its interrater reliability. METHOD: The Gross Motor Function
      Classification in MLD (GMFC-MLD) was modelled analogous to the Gross Motor
      Function Classification System in cerebral palsy. Motor data from 59 individuals
      (27 male; 32 female) with MLD (21 late infantile; 38 juvenile) born between 1970
      and 2007 were gathered from a nationwide survey and classified by six independent
      raters. Median age at onset was 17 months (range 9-27 mo) for the late infantile
      group and 74 months (35-168 mo) for the juvenile group. RESULTS: The GMFC-MLD
      consists of seven levels and is applicable from the age of 18 months. It
      represents all clinically relevant stages from normal (level 0) to loss of all
      gross motor function (level 6). The kappa coefficient was 0.90 for overall rater
      agreement. There were no significant differences between level-specific kappa
      coefficients. INTERPRETATION: The GMFC-MLD is a highly reliable, feasible tool
      for standardized assessment of gross motor function in MLD which can be used for
      the description of the natural course of the disease and for evaluation of
      therapeutic options such as stem cell transplantation and enzyme replacement,
      both of which are topics of current research.

PMID- 21087234
TI  - Pre-existing neurodevelopmental and neuropsychiatric difficulties in children
      with brain tumours: implications for future outcome studies.

PMID- 21087235
TI  - Aetiology of intellectual disability in paediatric outpatients in Northern India.
AB  - AIM: To study the aetiology of intellectual disability in patients presenting to
      hospital and the diagnostic yield of a standardized examination. METHOD: Over a 1
      year period, the first three children presenting to the paediatric outpatients
      department (OPD) on 2 selected weekdays with developmental delay, suspected
      intellectual disability, or school failure were enrolled for study if they
      satisfied standard definitions of global developmental delay (GDD), or
      intellectual disability as tested by scales for Indian children: Developmental
      Assessment for Indian Infants, Binet Karnat Test, and the Vineland Social
      Maturity Scale (Malin's Adaptation). Detailed history, and physical and
      neurological examinations were recorded. An algorithmic approach to
      investigations was followed. Also, neuroimaging, thyroid function,
      electroencephalograph, karyotyping, and studies for fragile-X syndrome were
      conducted. Aetiological diagnosis was considered established only if clinical
      features were supported by investigations. Clinical features associated with a
      successful aetiological diagnosis were computed. RESULTS: A total of 122 children
      were enrolled in a cross-sectional analytic study (mean age 43.5 mo [SD 40.66];
      84 males, 38 females). Of these, a definite aetiology could be assigned in 66
      children (54.1%); 17 prenatal, 38 perinatal/neonatal, and 11 postneonatal.
      Factors associated with reaching a definite diagnosis included younger age at
      presentation, presence of seizures, microcephaly, adverse neonatal events, and
      abnormal motor signs. Clinical history and examination gave important clues to
      the aetiology in 89 (72.9%) patients. Neuroimaging was abnormal in 91 out of 114
      children, with aetiological findings in 48 children. INTERPRETATION:
      Perinatal/neonatal causes predominate as the cause of GDD or intellectual
      disability in India. The study highlights that a large majority of cases seen
      here were preventable.

PMID- 21087236
TI  - From stem cells to neural networks: recent advances and perspectives for
      neurodevelopmental disorders.
AB  - Embryonic or induced pluripotent stem cells, available in mouse and human, have
      emerged as powerful tools to address complex questions in neurobiology. This
      review focuses on major advances relating to brain development and developmental
      disorders. Stem cells can differentiate into many different neuronal subtypes
      using in vitro models mimicking relevant in vivo developmental processes, and the
      underlying molecular and cellular mechanisms. Disease-specific human embryonic
      stem cells (ESCs) and induced pluripotent stem (iPS) cells are now available and
      allow for the study in vitro of the pathophysiology of degenerative and
      neurodevelopmental hereditary and sporadic disorders, including in the near
      future those of the human cortex. Finally, some recent studies have shown that
      stem cell-derived neural progenitors and neurons could help to rebuild damaged
      brain circuitry, opening the possibility of cell therapy.

PMID- 21087237
TI  - The clinical relevance of selecting resting data at different points in an energy
      cost of walking test in cerebral palsy.
AB  - AIM: Energy cost of walking (ECOW) is defined as 'walking oxygen consumption
      minus resting oxygen consumption divided by speed', where 'resting' data can be
      obtained either at the start or cessation of a test. This study aimed to
      ascertain when resting data should be taken during an ECOW test in children with
      cerebral palsy (CP). METHOD: Resting oxygen consumption per unit mass (VO(2) )
      and heart rate were recorded in children without physical impairment (18 males,
      13 females; mean age 11 y [SD 2 y 1 mo]) and children with diplegic CP (18 males,
      13 females; mean age 11 y [SD 2 y 6 mo, Gross Motor Function Classification
      System levels I and II]) at three stages, namely pre- and posttest sitting and
      pretest standing before and after an 8-minute ECOW test using the Cosmed K4b.
      RESULTS: Heart rate and VO(2) differed significantly between groups and stages (p
      <= 0.05) except for heart rate in standing and posttest sitting in the unimpaired
      children and for VO(2) during pretest sitting between groups. These differences
      impacted on the calculation of non-dimensional net oxygen cost (NDNOC) and
      physiological cost index (PCI) in CP but not in the unimpaired group. PCI was
      correlated with NDNOC in CP but not in the unimpaired cohort. INTERPRETATION:
      Pretest sitting resting data appear to be the most appropriate for use in the
      calculation of NDNOC and PCI. PCI may still have relevance in pathology where
      walking efficiency is compromised.

PMID- 21087238
TI  - Neuronox versus BOTOX for spastic equinus gait in children with cerebral palsy: a
      randomized, double-blinded, controlled multicentre clinical trial.
AB  - AIM: The aim of this study was to evaluate the efficacy and safety of a newly
      manufactured botulinum toxin, Neuronox, compared with BOTOX for the treatment of
      the spastic equinus gait in children with cerebral palsy. METHOD: A total of 127
      children with cerebral palsy, aged 2 to 10 years, who presented at three
      university hospitals with spastic equinus gait were assessed for eligibility to
      participate in this double-blinded, randomized, controlled trial. Of the 119
      eligible participants (mean age 4.33 y; SD 2.07; 76 males and 43 females; 79 with
      diplegia and 40 with hemiplegia), 57 were classified as Gross Motor Function
      Classification System level I, 29 as level II, and 33 as level III. Participants
      were randomly assigned to receive an injection of Neuronox (n=60) or BOTOX (n=59)
      to the calf muscles at a dose of 4U/kg for those with hemiplegia and 6U/kg for
      those with diplegia. Assessments were performed at baseline (V1) and at 4 (V2),
      12 (V3), and 24 (V4) weeks after the intervention. The primary outcome measure
      was response rate at V3, with a positive response being defined as at least a 2
      point increase in the Physicians' Rating Scale (PRS) score. The non-inferiority
      margin was set as -20% for the difference in the response rate. The secondary
      outcome measures included PRS score, passive range of motion (PROM) of the ankle
      and knee, and Gross Motor Function Measure 88 (GMFM-88). Any adverse events were
      investigated for safety implications. RESULTS: The response rate of the Neuronox
      group at V3 was not inferior to that of the BOTOX group (90% lower limit=
      11.58%). There were significant improvements in PRS, PROM of ankle dorsiflexion,
      and GMFM scores at V2, V3, and V4 in both groups. The changes in PRS score were
      not statistically different between the two groups in serial evaluation (p=0.96).
      PROM of the ankle dorsiflexion increased without any significant difference
      between the two groups, either overall (p=0.56) or at each visit (V2, p=0.32; V3,
      p=0.66; V4, p=0.90). The increase in GMFM score in serial measurements were not
      significantly different between the two groups (p=0.16), whereas it was larger in
      the BOTOX group than in the Neuronox group at V2 and V4 (p=0.03 and 0.05
      respectively). The frequency of adverse events was not significantly different
      between the two groups (p=0.97), and drug-related complications of Neuronox
      treatment were not addressed. INTERPRETATION: The outcomes of Neuronox, based on
      PRS, proved to be as effective and safe as those of BOTOX for the treatment of
      spasticity in individuals with cerebral palsy.

PMID- 21087239
TI  - Paediatric electromyography in the modern world: a personal view.
AB  - Paediatric electromyography (EMG) is an invaluable diagnostic test for the
      investigation of neuromuscular disease, but its use is inconsistent between and
      within different countries. One perception is that the procedure is painful;
      however, in comparison with common investigations performed routinely in
      children, EMG is better tolerated. While some developments, such as those within
      clinical genetics, would appear to mark its demise, paradoxically the more
      genetic abnormalities that are discovered in conditions such as hereditary
      neuropathy, the more precise a delineation of the phenotype is required. EMG has
      particular strengths in the diagnosis of neuropathies, motor neuronopathy and
      neuromuscular transmission disorders such as myasthenia. Also, it can supplement
      the investigation of myopathies. Areas of development include the diagnosis of
      myasthenia, delineation of bulbar palsy as a cause of dysphagia, more accurate
      and earlier prediction of prognosis in neonatal brachial palsy and investigation
      of channelopathies. It is a valuable diagnostic tool in developed countries and
      those with limited resources.

PMID- 21087240
TI  - Gillette Functional Assessment Questionnaire 22-item skill set: factor and Rasch
      analyses.
AB  - AIM: To determine dimensionality and item-level properties of the Gillette
      Functional Assessment Questionnaire (FAQ) 22-item skill set using factor and
      Rasch analyses. METHOD: A retrospective review of parent-reported FAQ 22-item
      skill set data was conducted of 485 individuals (273 males, 212 females; mean age
      9 y 10 mo, SD 3 y 10 mo), including 289 with cerebral palsy and 196 with a
      variety of other neuromusculoskeletal conditions with orthopedic impairments.
      Factor analyses to validate unidimensionality of the skill set and Rasch analyses
      to determine relative item difficulty, item and test level information, and
      content coverage of the item set were performed. Differential item functioning
      analysis of sub-groups based on sex, diagnosis grouping, and age was conducted.
      Precision of score estimates for the item set was analyzed. RESULTS: The FAQ 22
      item skill set demonstrates unidimensional structure and good item fit
      statistics. No floor or ceiling effects were noted. Differential item functioning
      (DIF) based on age was noted for seven items, four items showed diagnosis group
      related DIF, and one item sex-related DIF. Precision was adequate in the mid
      range range of abilities. INTERPRETATION: Based on this analysis, the FAQ 22-item
      skill set is a hierarchical set of interval scaled items suitable for measuring
      locomotor skill ability in children.

PMID- 21087241
TI  - Early numeracy in cerebral palsy: review and future research.
AB  - Children with cerebral palsy (CP) often have problems with arithmetic, but the
      development of numerical abilities in these children has received only minor
      attention. In comparison, detailed accounts have been written on the arithmetic
      abilities of typically developing children, but a theoretical framework is still
      lacking. A promising perspective is the embodied cognition framework, which
      focuses on the influence of perception and action behaviours on cognition. We
      searched the literature to find the available studies on the early numeracy
      capacities of children with CP. We reviewed eight studies in which primary school
      aged children with CP with a verbal IQ of at least 70 participated. The selected
      studies showed that these children are regularly delayed in performing simple
      arithmetic operations compared with their typically developing peers. However,
      owing to the limited number of studies no definite conclusions can be drawn
      regarding the precursors and developmental trajectories of arithmetic abilities
      in children with CP. We argue that the embodied cognition framework is well
      suited to scrutinize the arithmetic abilities of children with CP and provide
      future directions for research.

PMID- 21087242
TI  - Early continuous video electroencephalography in neonatal stroke.
AB  - Perinatal stroke is the second most common cause of neonatal seizures, and can
      result in long-term neurological impairment. Diagnosis is often delayed until
      after seizure onset, owing to the subtle nature of associated signs. We report
      the early electroencephalographic (EEG) findings in a female infant with a
      perinatal infarction, born at 41 weeks 2 days and weighing 3.42 kg. Before the
      onset of seizures, the EEG from 3 hours after delivery demonstrated occasional
      focal sharp waves over the affected region. After electroclinical seizures, focal
      sharp waves became more frequent, complex, and of higher amplitude, particularly
      in 'quiet sleep'. In 'active sleep', sharp waves often disappeared. Diffusion
      weighted imaging confirmed the infarct, demonstrating left frontal and parietal
      diffusion restriction. At 9 months, the infant has had no further seizures, and
      neurological examination is normal. To our knowledge, this report is the first to
      describe the EEG findings in perinatal stroke before seizures, and highlights the
      evolution of characteristic background EEG features.

PMID- 21087243
TI  - Video-EEG monitoring: safety and adverse events in 507 consecutive patients.
AB  - PURPOSE: Video-electroencephalography (EEG) monitoring plays a central role in
      the presurgical evaluation of medically refractory epilepsies and the diagnosis
      of nonepileptic attack disorders (NEADs). The aim of this study was to analyze
      safety and adverse events (AEs) during video-EEG monitoring. METHODS: We
      retrospectively evaluated 596 video-EEG sessions in 507 patients (233 men, mean
      age 36 years, standard deviation = 14, range 9-80 years) within a 6-year period.
      AEs were examined in detail and their risk factors were assessed using multiple
      logistic regression analysis. KEY FINDINGS: Forty-four patients (9%) experienced
      53 AEs: 20 had psychiatric events (17 postictal psychosis, 2 panic attacks, 1
      interictal psychosis), 15 had injuries (14 falls with minor injuries, 2 falls
      with fractures, 2 fractures without fall, 1 fall with epidural hematoma), 10
      patients had 13 episodes of status epilepticus (SE), and one AE was treatment
      related (valproic acid--induced encephalopathy). Patients with AEs were older (p
      = 0.036) and had a longer duration of epilepsy (p = 0.019). All AEs resulted in a
      prolonged hospital stay (p < 0.001). Ninety-one percent of the AEs occurred
      within the first 4 days of monitoring. Independent risk factors were duration of
      epilepsy >17 years [odds ratio (OR) 3.096; 95% confidence interval (CI) 1.548
      6.189], a previous history of psychiatric illness (OR 16.882; 95% CI 5.469
      52.110), a history of seizure-related injuries (OR 3.542; 95% CI 1.069-11.739),
      or a history of SE (OR 3.334; 95% CI 1.297-8.565). SIGNIFICANCE:   The most
      common AEs were postictal psychosis, falls, and SE. Patients with an older age,
      long disease duration, psychiatric comorbidity, history of injuries, and SE have
      a higher risk.

PMID- 21087244
TI  - The effect of surgery in encephalopathy with electrical status epilepticus during
      sleep.
AB  - PURPOSE: We analyzed clinical and electroencephalography (EEG) outcomes of 13
      patients with pharmacoresistant encephalopathy with electrical status epilepticus
      during sleep (ESES) following epilepsy surgery. METHODS: All patients had
      symptomatic etiology of ESES and preoperative neuropsychological deterioration.
      Ten patients had daily atypical absences. Clinical outcome was assessed at 6
      months and at 2 years after surgery. Clinical and EEG data were reviewed
      retrospectively. The spike propagation pattern and area and source strength in
      source montage were analyzed from preoperative and postoperative EEG studies. KEY
      FINDINGS: Preoperative sleep EEG showed electrical status epilepticus during
      sleep (SES) with one-way interhemispheric propagation in nine patients and with
      two-way interhemispheric propagation in four. The age of the patients at the time
      of surgery ranged from 3.6-9.9 years. Focal resection (two patients) or
      hemispherotomy (one patient with postoperative EEG) either terminated SES or
      restricted the discharge to one region. Either reduced SES propagation area or
      source strength was found in four of eight callosotomy patients with
      postoperative EEG. Of patients who had seizures preoperatively, Engel class I-II
      seizure outcome was observed in two of three children after focal resection or
      hemispherotomy and in two of eight children after callosotomy. None of these
      patients with Engel class I-II outcome had SES with two-way interhemispheric
      propagation on preoperative EEG. Cognitive deterioration was halted
      postoperatively in all except one patient. Cognitive catch-up of more than 10 IQ
      points was seen in three patients, all of whom had shown a first measured IQ of
      >75. SIGNIFICANCE: Patients with pharmacoresistant ESES based on symptomatic
      etiology may benefit from resective surgery or corpus callosotomy regarding both
      seizure outcome and cognitive prognosis.

PMID- 21087245
TI  - Statistical mapping of ictal high-frequency oscillations in epileptic spasms.
AB  - PURPOSE: We assessed 636 epileptic spasms seen in 11 children (median 44 spasms
      per child) and determined the spatial and temporal characteristics of ictal high
      frequency oscillations (HFOs) in relation to the onset of spasms. METHODS:
      Electrocorticography (ECoG) signals were sampled from 104-148 cortical sites per
      child, and the dynamic changes of ictal HFOs were animated on each individual's
      three-dimensional (3D) magnetic resonance (MR) image surface. KEY FINDINGS:
      Visual assessment of ictal ECoG recordings revealed that each spasm event was
      characterized by augmentation of HFOs. Time-frequency analysis demonstrated that
      ictal augmentation of HFOs at 80-200 Hz was most prominent and generally preceded
      those at 210-300 Hz and at 70 Hz and slower. Recruitment of HFOs in the rolandic
      cortex preceded the clinical onset objectively visualized as electromyographic
      deflection. The presence or absence of ictal motor symptoms was related more to
      the amplitude of HFOs in the Rolandic cortex than in the seizure-onset zone. In a
      substantial proportion of epileptic spasms, seizure termination began at the
      seizure-onset zone and propagated to the surrounding areas; we referred to this
      observation as the "ictal doughnut phenomenon." Univariate analysis suggested
      that complete resection of the sites showing the earliest augmentation of ictal
      HFOs was associated with a good surgical outcome. SIGNIFICANCE: Recruitment of
      HFOs at 80-200 Hz in the rolandic area may play a role in determining seizure
      semiology in epileptic spasms. Our study using macroelectrodes demonstrated that
      ictal HFOs at 80-200 Hz preceded those at 210-300 Hz.

PMID- 21087246
TI  - Deficits in oculomotor performance in pediatric epilepsy.
AB  - PURPOSE: Given evidence of limitations in neuropsychological performance in
      epilepsy, we probed the integrity of components of cognition--including speed of
      processing, response inhibition, and spatial working memory--supporting executive
      function in pediatric epilepsy patients and matched controls. METHODS: A total of
      44 pairs of controls and medically treated pediatric epilepsy patients with no
      known brain pathology completed cognitive oculomotor tasks, computerized
      neuropsychological testing, and psychiatric assessment. KEY FINDINGS: Patients
      showed slower reaction time to initiate a saccadic response compared to controls
      but had intact saccade accuracy. Cognitively driven responses including response
      inhibition were impaired in the patient group. Patients had increased incidence
      of comorbid psychopathology, but comorbidity did not predict worse functioning
      compared to patients with no Attention Deficit Hyperactivity Disorder (ADHD).
      Epilepsy type and medication status were not predictive of outcome. More complex
      neuropsychological performance was impaired in tasks requiring visual memory and
      sequential processing, which was correlated with inhibitory control and
      antisaccade accuracy. SIGNIFICANCE: Pediatric epilepsy may be associated with
      vulnerabilities that specifically undermine speed of processing and response
      inhibition but not working memory, and may underlie known neuropsychological
      performance limitations. This particular profile of abnormalities may be
      associated with seizure-mediated compromises in brain maturation early in
      development.

PMID- 21087247
TI  - Development and reliability of a correction factor for parent-reported adherence
      to pediatric antiepileptic drug therapy.
AB  - PURPOSE: Study aims were (1) to document and examine associations between parent
      report and electronic monitoring (EM) of pediatric antiepileptic drug (AED)
      adherence, (2) to determine the sensitivity and specificity of parent-reported
      adherence, and (3) to develop a correction factor for parent-reported adherence.
      METHODS: Participants included 111 consecutive children with new-onset epilepsy
      (M(age) = 7.2 +/- 2.0; 61.3% male; 75.8% Caucasian) and their primary caregivers.
      AED adherence was electronically monitored for 3 months prior to the 4-month
      clinic follow-up visit. Parent-reported adherence captured adherence 1-week prior
      to the clinic visit. For specificity/sensitivity analyses of parent-reported
      adherence, cut points of 50%, 80%, and 90% were used with electronically
      monitored adherence calculated 1-week prior to the clinic visit as the reference
      criterion. KEY FINDINGS: Electronically monitored adherence (80.3%) was
      significantly lower than parent-reported adherence (96.5%; p < 0.0001) 1-week
      prior to the clinic visit, but both were significantly correlated (rho = 0.46, p
      < 0.001). The 90% parent-reported adherence cut point demonstrated the most
      sensitivity and specificity to electronically monitored adherence; however,
      specificity was still only 28%. A correction factor of 0.83 was identified as a
      reliable adjustment for parent-reported adherence when compared to electronically
      monitored adherence. SIGNIFICANCE: Although EM is the gold standard of adherence
      measurement for pediatric epilepsy, it is often not clinically feasible to
      integrate it into routine clinical care. Therefore, use of a correction factor
      for interpreting parent-reported adherence holds promise as a reliable clinical
      tool. With reliable adherence measurement, clinicians can provide adherence
      interventions with the hope of optimizing health outcomes for children with
      epilepsy.

PMID- 21087248
TI  - River-induced flow dynamics in long-screen wells and impact on aqueous samples.
AB  - Previously published field investigations and modeling studies have demonstrated
      the potential for sample bias associated with vertical wellbore flow in
      conventional monitoring wells constructed with long-screened intervals. This
      article builds on the existing body of literature by (1) demonstrating the
      utility of continuous (i.e., hourly measurements for ~1 month) ambient wellbore
      flow monitoring and (2) presenting results from a field experiment where
      relatively large wellbore flows (up to 4 L/min) were induced by aquifer
      hydrodynamics associated with a fluctuating river boundary located approximately
      250 m from the test well. The observed vertical wellbore flows were strongly
      correlated with fluctuations in river stage, alternating between upward and
      downward flow throughout the monitoring period in response to changes in river
      stage. Continuous monitoring of ambient wellbore flows using an electromagnetic
      borehole flowmeter allowed these effects to be evaluated in concert with
      continuously monitored river-stage elevations (hourly) and aqueous uranium
      concentrations (daily) in a long-screen well and an adjacent multilevel well
      cluster. This study demonstrates that when contaminant concentrations within the
      aquifer vary significantly over the depth interval interrogated, river-induced
      vertical wellbore flow can result in variations in measured concentration that
      nearly encompass the full range of variation in aquifer contaminant concentration
      with depth.

PMID- 21087249
TI  - A simple method to hide data loggers safely in observation wells.
AB  - Submersible data loggers are widely used for groundwater monitoring, but their
      application often runs the risk of hardware and data loss through vandalism or
      theft. During a field study in India, the authors of this article experienced
      that well locks attract the attention of unauthorized persons and do not provide
      secure protection in unattended areas. To minimize the risk of losing data
      loggers, a cheap and simple solution has been invented to hide the instruments
      and associated attachments below the ground surface, inside observation wells. It
      relies on attaching the logger to a length of small-diameter pipe that is
      submerged at the bottom of the well, instead of attaching it to the top of the
      well. The small-diameter pipe with the logger is connected to a small bottle
      containing a magnet that floats on the water surface of the well and can be
      recovered using another bottle also with a magnet. A logger that is concealed in
      this way is difficult to detect and access without knowledge of the method and
      adequate removal tools. The system was tested and successfully applied for
      monitoring shallow observation wells at three field sites in Greater Delhi,
      India.

PMID- 21087250
TI  - Coherence among climate signals, precipitation, and groundwater.
AB  - Climate signals may affect groundwater level at different time scales in
      different geographical regions, and those patterns or time scales can be
      estimated using coherence analysis. This study shows that the synthesis effort
      required to search for patterns at the physical geography scale is possible, and
      this approach should be applicable in other regions of the world. The relations
      between climate signals, Southern Oscillation Index, Pacific Decadal Oscillation,
      North Atlantic Oscillation, North Pacific Pattern (SOI, PDO, NAO, and NP),
      precipitation, and groundwater level in three geographical areas of Wisconsin are
      examined using a three-tiered coherence analysis. In the high frequency band (<4(
      1) cycles/year), there is a significant coherence between four climate signals
      and groundwater level in all three areas. In the low frequency band (>8(-1) to
      <=23(-1) cycles/year), we found significant coherence between the SOI and NP
      signals and groundwater level in the forested area, characterized by shallow
      wells constructed in sand and gravel aquifers. In the high frequency band, there
      is significant coherence between the four climate signals and precipitation in
      all three areas. In the low frequency band, the four climate signals have effect
      on precipitation in the agricultural area, and SOI and NP have effect on
      precipitation in the forested and driftless areas. Precipitation affects
      groundwater level in all three areas, and in high, low and intermediate frequency
      bands. In the agricultural area, deeper aquifers and a more complex
      hydrostratigraphy and land use dilute the effect of precipitation on groundwater
      level for interdecadal frequencies.

PMID- 21087251
TI  - Effects of multiscale anisotropy on basin and hyporheic groundwater flow.
AB  - Various subsurface flow systems exhibit a combination of small-scale to large
      scale anisotropy in hydraulic conductivity (K). The large-scale anisotropy
      results from systematic trends (e.g., exponential decrease or increase) of K with
      depth. We present a general two-dimensional solution for calculation of
      topography-driven groundwater flow considering both small- and large-scale
      anisotropy in K. This solution can be applied to diverse systems with arbitrary
      head distribution and geometry of the water table boundary, such as basin or
      hyporheic flow. In a special case, this solution reduces to the well-known Toth
      model of uniform isotropic basin. We introduce an integral measure of flushing
      intensity that quantifies flushing at different depths. Using this solution, we
      simulate heads and streamlines and provide analyses of flow structure in the flow
      domain, relevant to basin analyses or hyporheic flow. It is shown that
      interactions between small-scale anisotropy and large-scale anisotropy strongly
      control the flow structure. In the classic Toth flow model, the flushing
      intensity curves exhibit quasi-exponential decrease with depth. The new measure
      is capable of capturing subtle changes in the flow structure. Our study shows
      that both small- and large-scale anisotropy characteristics have substantial
      effects that need to be integrated into analysis of topography-driven flow.

PMID- 21087252
TI  - Confined aquifer loading: implications for groundwater management.

PMID- 21087254
TI  - Implementation of California state school competitive food and beverage
      standards.
AB  - BACKGROUND: Competitive foods and beverages are available on most US school
      campuses. States and school districts are adopting nutrition standards to
      regulate these products, but few studies have reported on the extent to which
      schools are able to adhere to competitive regulations. The purpose of this study
      was to describe the extent to which schools in disadvantaged communities were
      able to implement California competitive food and beverage standards. METHODS:
      Data on the competitive foods (n = 1019) and beverages (n = 572) offered for sale
      on 19 school campuses were collected in 2005 and 2008. Descriptive statistics
      were generated on overall adherence rates to school nutrition standards and
      adherence rates by venue and school level. Logistic regression models tested
      predictors of adherence by continuous and categorical variables (eg, venue, item
      selling price). RESULTS: Data show an increase from 2005 to 2008 in average
      adherence to the California standards. Several predictors had statistically
      significant associations with adherence or nonadherence. Adherence was higher for
      competitive foods sold in school stores than foods sold in vending machines.
      Higher selling price was associated with lower adherence. Competitive foods
      classified as entrees were more likely to adhere than snack items, and larger
      total size (in fluid ounces) beverages were associated with higher adherence.
      CONCLUSIONS: Schools have begun to implement competitive food and beverage
      policies. However, school environments, particularly in secondary schools, are
      not 100% compliant with school nutrition standards. These findings can inform
      policymakers and school officials about the feasibility of implementing
      competitive food standards in schools.

PMID- 21087253
TI  - Physical education resources, class management, and student physical activity
      levels: a structure-process-outcome approach to evaluating physical education
      effectiveness.
AB  - BACKGROUND: This study was conducted to empirically evaluate specific human,
      curricular, and material resources that maximize student opportunities for
      physical activity during physical education (PE) class time. A structure-process
      outcome model was proposed to identify the resources that influence the frequency
      of PE and intensity of physical activity during PE. The proportion of class time
      devoted to management was evaluated as a potential mediator of the relations
      between resource availability and student activity levels. METHODS: Data for this
      cross-sectional study were collected from interviews conducted with 46 physical
      educators and the systematic observation of 184 PE sessions in 34 schools.
      Regression analyses were conducted to test for the main effects of resource
      availability and the mediating role of class management. RESULTS: Students who
      attended schools with a low student-to-physical educator ratio had more PE time
      and engaged in higher levels of physical activity during class time. Access to
      adequate PE equipment and facilities was positively associated with student
      activity levels. The availability of a greater number of physical educators per
      student was found to impact student activity levels by reducing the amount of
      session time devoted to class management. CONCLUSION: The identification of
      structure and process predictors of student activity levels in PE will support
      the allocation of resources and encourage instructional practices that best
      support increased student activity levels in the most cost-effective way
      possible. Implications for PE policies and programs are discussed.

PMID- 21087255
TI  - A review of gastrointestinal outbreaks in schools: effective infection control
      interventions.
AB  - BACKGROUND: The purpose of this study was to review documented outbreaks of
      gastrointestinal illness in schools, published in the last 10 years, to identify
      etiology, mode of transmission, the number of children affected, morbidity and
      mortality patterns, and interventions for control and prevention. METHODS:
      Searches of electronic databases, public health publications, and federal, state,
      and provincial public health Web sites were completed. RESULTS: Of the 121
      outbreaks that met the inclusion criteria, 51% were bacterial, 40% viral, 7% were
      from Cryptosporidium, and 2% from multiple organisms. Transmission routes
      recorded in 101 reports included foodborne (45%), person-to-person (16%),
      waterborne (12%), and animal contact (11%). Actions to control outbreaks included
      alerting medical and public health authorities or the community to the outbreak
      (13%), treating cases (12%), enhancing hand washing (11%), and increased
      vigilance during food preparation (8%). Recommendations to prevent future
      outbreaks were compared with previously published studies that demonstrated
      effectiveness. CONCLUSIONS: The risk of foodborne illness was reduced when food
      handlers practiced effective hand washing technique and received food safety
      training and certification. Student training programs on hand hygiene, enhanced
      cleaning and disinfection of the school, and hepatitis A vaccination were found
      effective. Children should be supervised on farm visits, hand washing strictly
      enforced, and food eaten in an area separated from the animals. Staff and
      students should have a positive, continuous communication with public health
      authorities including educational sessions and immediate reporting of possible
      outbreaks.

PMID- 21087256
TI  - Variation in school health policies and programs by demographic characteristics
      of US schools, 2006.
AB  - BACKGROUND: To identify whether school health policies and programs vary by
      demographic characteristics of schools, using data from the School Health
      Policies and Programs Study (SHPPS) 2006. This study updates a similar study
      conducted with SHPPS 2000 data and assesses several additional policies and
      programs measured for the first time in SHPPS 2006. METHODS: SHPPS 2006 assessed
      the status of 8 components of the coordinated school health model using a
      nationally representative sample of public, Catholic, and private schools at the
      elementary, middle, and high school levels. Data were collected from school
      faculty and staff using computer-assisted personal interviews and then linked
      with extant data on school characteristics. RESULTS: Results from a series of
      regression analyses indicated that a number of school policies and programs
      varied by school type (public, Catholic, or private), urbanicity, school size,
      discretionary dollars per pupil, percentage of white students, percentage of
      students qualifying for free lunch funds, and, among high schools, percentage of
      college-bound students. Catholic and private schools, smaller schools, and those
      with low discretionary dollars per pupil did not have as many key school health
      policies and programs as did schools that were public, larger, and had higher
      discretionary dollars per pupil. However, no single type of school had all key
      components of a coordinated school health program in place. CONCLUSIONS: Although
      some categories of schools had fewer policies and programs in place, all had both
      strengths and weaknesses. Regardless of school characteristics, all schools have
      the potential to implement a quality school health program.

PMID- 21087257
TI  - Cyberbullying and self-esteem.
AB  - BACKGROUND: This article examines the relationship between middle school
      students' experience with cyberbullying and their level of self-esteem. Previous
      research on traditional bullying among adolescents has found a relatively
      consistent link between victimization and lower self-esteem, while finding an
      inconsistent relationship between offending and lower self-esteem. It is
      therefore important to extend this body of research by determining how bullying
      augmented through the use of technology (such as computers and cell phones) is
      linked to differing levels of self-esteem. METHODS: During March and April 2007,
      a random sample of 1963 middle school students (mean age 12.6) from 30 schools in
      one of the largest school districts in the United States completed a self-report
      survey of Internet use and cyberbullying experiences. RESULTS: This work found
      that students who experienced cyberbullying, both as a victim and an offender,
      had significantly lower self-esteem than those who had little or no experience
      with cyberbullying. CONCLUSIONS: A moderate and statistically significant
      relationship exists between low self-esteem and experiences with cyberbullying.
      As such, bullying prevention programs incorporated in school curricula should
      also include substantive instruction on cyberbullying. Moreover, educators need
      to intervene in cyberbullying incidents, as failure to do so may impact the
      ability of students to be successful at school.

PMID- 21087259
TI  - Invasive forbs differ functionally from native graminoids, but are similar to
      native forbs.
AB  - * Exotic plant invasions can alter ecosystem processes, particularly if the
      invasive species are functionally different from native species. We investigated
      whether such alterations can be explained by differences in functional traits
      between native and invasive plants of the same functional group or by differences
      in functional group affiliation. * We compared six invasive forbs in Europe with
      six native forbs and six native graminoids in leaf and whole-plant traits,
      plasticity in response to nutrient supply and interspecific competition, litter
      decomposition rate, effects on soil nutrient availability, and allelopathy. All
      traits were measured in a series of pot experiments, and leaf traits additionally
      in the field. * Invasive forbs differed from native forbs for only a few traits;
      they had less leaf chlorophyll and lower phosphorus (P) uptake from soil, but
      they tended to have a stronger allelopathic effect. The invasive forbs differed
      in many traits from the native graminoids, their leaves had lower tissue
      densities and a shorter life span, their litter decomposed faster and they had a
      lower nitrogen-use efficiency. * Our results suggest that invasive forbs have the
      potential to alter ecosystem properties when invading graminoid-dominated and
      displacing native graminoids but not when displacing native forbs.

PMID- 21087260
TI  - Relationship between gibberellin, ethylene and nodulation in Pisum sativum.
AB  - * Gibberellin (GA) deficiency resulting from the na mutation in pea (Pisum
      sativum) causes a reduction in nodulation. Nodules that do form are aberrant,
      having poorly developed meristems and a lack of enlarged cells. Studies using
      additional GA-biosynthesis double mutants indicate that this results from severe
      GA deficiency of the roots rather than simply dwarf shoot stature. * Double
      mutants isolated from crosses between na and three supernodulating pea mutants
      exhibit a supernodulation phenotype, but the nodule structures are aberrant. This
      suggests that severely reduced GA concentrations are not entirely inhibitory to
      nodule initiation, but that higher GA concentrations are required for proper
      nodule development. * na mutants evolve more than double the amount of ethylene
      produced by wild-type plants, indicating that low GA concentrations can promote
      ethylene production. The excess ethylene may contribute to the reduced nodulation
      of na plants, as application of an ethylene biosynthesis inhibitor increased na
      nodule numbers. However, these nodules were still aberrant in structure. *
      Constitutive GA signalling mutants also form significantly fewer nodules than
      wild-type plants. This suggests that there is an optimum degree of GA signalling
      required for nodule formation and that the GA signal, and not the concentration
      of bioactive GA per se, is important for nodulation.

PMID- 21087261
TI  - Water quality as a threat to aquatic plants: discriminating between the effects
      of nitrate, phosphate, boron and heavy metals on charophytes.
AB  - * Eutrophication is a threat to wetlands worldwide. Elevated phosphorus
      concentration is often the main driver of loss of biodiversity and ecosystem
      function, but effects of phosphorus and nitrogen have proved largely inseparable,
      because they vary colinearly. Charophytes, aquatic algae that are very close to
      the evolutionary link with the land-plant lineage, provide a sensitive system for
      disentangling complex pollutant threats. * Here, we investigated aquatic
      vegetation and water quality at the principal sites for charophyte biodiversity
      in the UK and used hierarchical partitioning to discriminate independent effects
      of pollutants on their occurrence. A laboratory experiment examined the growth
      responses of a representative species (Chara globularis) to nitrate. * Nitrate-N
      exerted the greatest detrimental effect on charophyte occurrence in the field.
      Furthermore, growth of C. globularis in the laboratory was inhibited above very
      low concentrations. Smaller independent effects of copper (Cu), cadmium (Cd),
      cobalt (Co), phosphate-P, nickel (Ni), boron (B) and manganese (Mn) on charophyte
      occurrence were discriminated. * It is possible to separate the deleterious
      effects of phosphorus and nitrogen on aquatic organisms in the field. Nitrate is
      a critical factor and a mean annual average concentration limit of c. 2 mg l-1
      nitrate-N is necessary to protect charophytes and their services within wetland
      ecosystems.

PMID- 21087262
TI  - Innate immunity: has poplar made its BED?
AB  - The perennial plant model species Populus trichocarpa has received considerable
      attention in the last 5 yr because of its potential use as a bioenergy crop. The
      completion of its genome sequence revealed extensive homologies with the
      herbaceous annual species Arabidopsis thaliana. This review highlights the
      similarities and differences at the qualitative defence response components
      level, notably in putative NBS-LRR protein content and downstream defence
      regulators. With almost a twofold NBS-LRR gene complement compared with A.
      thaliana, P. trichocarpa also encodes some putative R-proteins with unusual
      architectures and possible DNA-binding capacity. P. trichocarpa also possesses
      all the known main components characteristic of TIR-NB-LRR and CC-NB-LRR
      signalling. However, very little has been done with regard to the components
      involved in the poplar qualitative response to pathogens. In addition, the
      relationship between plant-biotroph perception/signalling and the role of
      salicylic acid, an important defence compound, remains uncertain. This review
      aims to identify the genomic components present in poplar that could potentially
      participate in the qualitative response and highlights where efforts should be
      devoted to obtain a better understanding of the poplar qualitative defence
      response.

PMID- 21087264
TI  - Temperature-dependent changes in Photosystem II heterogeneity of attached leaves
      under high light.
AB  - Attached leaves of pumpkin (Cucurbita pepo L. cv. Jattilaismeloni) were exposed
      to high light intensity at room temperature (ca 23 degrees C) and at 1 degrees C.
      Fluorescence parameters and electron transport activities measured from isolated
      thylakoids indicated faster photoinhibition of PSII at low temperature.
      Separation of the alpha and beta components of the complementary area above the
      fluorescence induction curve of dichlorophenyl-dimethylurea-poisoned thylakoids
      revealed that at low temperature only the alpha-centers declined during exposure
      to high light intensity while the content of functional beta-centers remained
      constant. Freeze-fracture electron microscopy showed no decrease in the density
      of particles on the appressed exoplasmic fracture face, indicating that the
      photoinhibited alpha-centers remained in the appressed membranes at 1 degrees C.
      Because of the function of the repair and protective mechanisms of PSII, strong
      light induced less photoinhibition at room temperature, but more complicated
      changes occurred in the alpha/beta-heterogeneity of PSII. During the first 30 min
      at high light intensity the decrease in alpha-centers was almost as large as at 1
      degrees C, but in contrast to the situation at low temperature the decrease in
      alpha-centers was compensated for by a significant increase in PSIIbeta-centers.
      Changes in the density and size of freeze-fracture particles suggest that this
      increase in beta-centers was due to migration of phosphorylated light-harvesting
      complex from appressed to non-appressed thylakoid membranes while the PSII core
      remained in the appressed membranes. This situation, however, was only transient
      and was followed by a rapid decrease in the functionalbeta-centers.

PMID- 21087263
TI  - SOS3 mediates lateral root development under low salt stress through regulation
      of auxin redistribution and maxima in Arabidopsis.
AB  - * The SOS signaling pathway plays an important role in plant salt tolerance.
      However, little is known about how the SOS pathway modulates organ development in
      response to salt stress. Here, the involvement of SOS signaling in NaCl-induced
      lateral root (LR) development in Arabidopsis was assessed. * Wild-type and sos3-1
      mutant seedlings on iso-osmotic concentrations of NaCl and mannitol were
      analyzed. The marker lines for auxin accumulation, auxin transport, cell division
      activity and stem cells were also examined. * The results showed that ionic
      effect alleviates the inhibitory effects of osmotic stress on LR development. LR
      development of the sos3-1 mutant showed increased sensitivity specifically to low
      salt. Under low-salt conditions, auxin in cotyledons and LR primordia (LRP) of
      the sos3-1 mutant was markedly reduced. Decreases in auxin polar transport of
      mutant roots may cause insufficient auxin supply, resulting in defects not only
      in LR initiation but also in cell division activity in LRP. * Our data uncover a
      novel role of the SOS3 gene in modulation of LR developmental plasticity and
      adaptation in response to low salt stress, and reveal a new mechanism for plants
      to sense and adapt to small changes of salt.

PMID- 21087265
TI  - Assessment of the potential of the blue light gradient in soybean pulvini as a
      leaf orientation signal.
AB  - Blue light gradients in the pulvini of soybean (Glycine max var. Northrup King
      S1346) leaves with different laminar orientations were examined with a fiber
      optic microprobe. The gradients changed markedly as a function of both incident
      light angle and leaf position and were determined largely by the amount of light
      present in the adaxial side of the pulvinus. The steepest gradient for inclined
      leaves was with light incident at 90 degrees  whereas for declined leaves it
      occurred when the light was incident at 150 degrees . A proposed pulvinar
      mechanism which allows for the detection of light direction and leaf position by
      using the blue light gradient as an orientation signal could account for solar
      tracking by soybean.

PMID- 21087266
TI  - Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings.
AB  - Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the
      cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe
      transport was measured and its tissue distribution determined. In the mesocotyl,
      there is an apoplastic barrier between cortex and stele. This barrier creates two
      apoplastic domains which are non-communicating. A kinetic barrier exists between
      the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic
      barrier is not absolute and there is limited communication between the apoplasts
      of the two regions. This kinetic barrier effectively creates two sub-domains. In
      the coleoptile, there is communication between the apoplast of the vascular
      strands and that of the surrounding cortical tissue. No apoplastic communication
      was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the
      apoplastic space of the coleoptile cortex is a sub-domain of the integrated
      coleoptile domain and is separate from that of the apoplastic domain of the
      mesocotyl cortex.

PMID- 21087267
TI  - Tissue to tissue symplastic communication in the shoots of etiolated corn
      seedlings.
AB  - Carboxyfluorescein, a symplastic probe, was applied to the cut mesocotyl base or
      coleoptile apex of etiolated Zea mays cv. Silver Queen seedlings and its
      transport measured and tissue distribution determined. Long-distance longitudinal
      symplastic transport of the carboxyfluorescein was mainly in the vascular stele.
      It moved laterally from the mesocotyl stele to the mesocotyl cortex but the
      presence of a weak barrier limited the movement. A partial symplastic barrier was
      also present near the coleoptile-mesocotyl node.

PMID- 21087268
TI  - Distribution of isoflavones in lupin hypocotyls. Possible control of cell wall
      peroxidase activity involved in lignification.
AB  - The distribution of 4 key isoflavones (luteone, genistein, 2'-hydroxygenistein
      and wighteone) in lupin (Lupinus albus L. cv. multolupa) hypocotyls shows a
      gradient that diminishes from young to old tissues. A spatial gradient occurs
      within the hypocotyl, and a temporal gradient in both the outermost vascular and
      epidermal tissues. Not only does a gradient exist in respect to the quantity of
      isoflavones, but there is also a gradient in respect to the type of isoflavone.
      Thus, wighteone is mainly associated with the non-meristematic zones of the lupin
      hypocotyl. A close relationship was found between the distribution and the
      localization in the walls of phloem cells of both peroxidase (EC 1.11.1.7) and
      isoflavones. This observation suggests an in vivo peroxidase-isoflavone
      interconnection. In fact, lupin isoflavones are able to inhibit the peroxidase
      catalyzed oxidation of the lignin precursor coniferyl alcohol, probably due to
      the co-oxidation of isoflavones in the reaction media. The results are discussed
      on the basis of a possible role for isoflavones in controlling cell
      wallperoxidase activity involved in the lignification of phloem cells.

PMID- 21087269
TI  - Photoinhibition at chilling temperatures and effects of freezing stress on cold
      acclimated spinach leaves in the field. A fluorescence study.
AB  - The role of high light stress in a natural environment was studied on spinach
      plants (Spinacia oleracea L. cv. Wolter) grown in the field during the winter
      season. Fluorescence induction (at 293 K and 77 K) of leaves was used to
      characterize the stress effects. Night frost with minimum temperatures between -
      1.5 degrees C and -7.5 degrees C (i.e. above the'frost killing point'at ca. -11.5
      degrees C) led to impaired photosynthesis. This was seen as increased initial
      fluorescence (F(o) ), decreased ratio of variable to maximum fluorescence (F(V)
      /F(M) ) and lowered rates of O(2) evolution. The freezing injury was reversible
      within several frostless days. Exposure to high light (about 900 mol m(-2) s(-1)
      ) at chilling temperatures in the field caused photoinhibition, manifested as
      decreased variable fluorescence (F(V) ) and F(V) /F(M) ratio without changes in
      F(O) . The photoinhibitory fluorescence quenching was not stronger after frost
      than after frostless nights; synergism between light stress and preceding
      freezing stress was not observed. Fluorescence induction signals at 77 K showed
      that F(V) of photosystems I and II decreased to the same extent, indicating
      increased thermal deactivation of excited chlorophyll. Photoinhibition was fully
      reversible at +4 degrees C within 1 h in low light, but only partially in
      moderate light. Preceding night frosts did not affect the recovery. The
      photoinhibition observed here is regarded as a protective system of thermal
      dissipation of excess light energy.

PMID- 21087270
TI  - Purification of an anionic isoperoxidase from peach seeds and its immunological
      comparison with other anionic isoperoxidases.
AB  - A soluble anionic isoperoxidase (EC 1,11,1,7) was purified from peach (Prunus
      persica L. Batsch cv. Merry) seeds. Purification was achieved by DEAE-Sephacel,
      Sephacryl S-300 and CM-cellulose chromatography. The purified isoperoxidase de
      carboxylated indole-3-acetic acid (S(0.5) 0.13 mM, Hill coefficient 1.7).
      Molecular mass, determined by gel filtration and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, was ca 60 kDa. Polyclonal antibodies were
      raised in rabbit against this isoperoxidase. Using immunoprecipitation this
      isoenzyme was found to be immunologically different from other soluble anionic
      isoperoxidases isolated from peach seeds.

PMID- 21087271
TI  - Relation between relative growth rate, endogenous gibberellins, and the response
      to applied gibberellic acid for Plantago major.
AB  - Relationships between relative growth rate (RGR), endogenous gibberellin (GA)
      concentration and the response to application of gibberellic acid (GA(3) ) were
      studied for two inbred lines of Plantago major L., which differed in RGR. A4, the
      fast-growing inbred line, had a higher free GA concentration than the slow
      growing W9, as analyzed by enzyme immunoassay. GA(3) application increased total
      plant weight and RGR(3) particularly for the slow-growing line. Chlorophyll a
      content and photosynthetic activity per unit leaf area were decreased, while
      transpiration rate was unaffected by GA(3) application. The increase in RGR by
      GA(3) application was associated with an increased leaf weight ratio; specific
      leaf area and percentage of dry matter in the leaves were only temporarily
      affected. Root respiration rate per unit dry weight was unaffected. The
      correlation between low RGR, low GA concentration and high responsiveness to
      applied GA(3) supports the contention that gibberellins are involved in the
      regulation of RGR. However, the transient influence of GA(3) application on some
      growth components suggests the involvement of other regulatory factors in
      addition to GA.

PMID- 21087272
TI  - Failure to corroborate claims that the developing endosperm of wheat (Triticum
      aestivum) contains significant activities of fructose-1,6-bisphosphatase.
AB  - This work was done to test claims (Sangwan and Singh, Physiol. Plant. 73: 21-26)
      that the developing endosperm of wheat (Triticum aestivum L.) contains a
      cytosolic and a plastidic fructose- 1,6-bisphosphatase (EC 3.1.3.11; FBPase).
      Repetition of the procedure of Sangwan and Singh with extracts of developing
      endosperm of Triticum aestivum cv. Mercia produced two peaks of apparent FBPase
      activity on elution from DEAE-cellulose. Both peaks showed high activity of
      pyrophosphate:fructose-6-phos-phate 1-phosphotransferase [EC 2.7.1.90; PFK(PP(i)
      )]. The apparent FBPase activity in both peaks was stimulated by 20 MUM fructose
      2,6-bisphosphate and inhibited by antibodies to PFK(PP(i) ). Antibody to
      plastidic FBPase did not react positively in an immunoblot analysis with any
      protein of M(r) comparable to that of known FBPase in either peak. It is argued
      that the ability of each peak to convert fructose-1,6-bisphosphate to fructose-6
      phosphate was due to PFK(PP(i) ). and that there remains no substantiated
      evidence for the presence of a plastidic FBPase in the developing endosperm of
      wheat.

PMID- 21087273
TI  - Plastid microtubule-like structures in wheat are insensitive to microtubule
      inhibitors.
AB  - The effects of microtubule inhibitors on the spectral properties of leaves of
      wheat (Triticum aestivum L. cv. Walde) and on the presence of plastid microtubule
      like structures (MTLS) during etioplast to chloroplast transformation were
      examined. Amiprophos-methyl (APM, 0.1 mM), fed to leaf sections of 7-day-old dark
      grown wheat, reduced the ration of phototransformable to non-phototransformable
      proto-chlorophyllide (PChlide), decreased the rate of the Shibata shift, and
      inhibited chlorophyll accumulation and grana stacking. The spectral properties of
      isolated etioplasts were not affected by APM. Colchicine (10 mM), fed to leaf
      sections, inhibited greening but had no effect on the PChlide ratio or the
      Shibata shift. MTLS were still visible on electron micrographs after treatment
      with APM or colchicine at frequencies similar to controls. A third inhibitor,
      vinblastine, had no effect on the spectral properties of non-irradiated or
      irradiated etiolated leaves except at concentrations that produced visible tissue
      damage before the irradiation. The effects of APM and colchicine may reflect
      inhibitions of respiration and protein synthesis, respectively. It is concluded
      that MTLS are insensitive to microtubule inhibitors and thus are probably not
      composed of tubulin.

PMID- 21087274
TI  - Effect of low growth temperature on coupling between electron transport and
      proton flux in Vicia faba thylakoids.
AB  - Coupling between electron transport and proton flux has been compared in
      chloroplasts from Vicia faba (cv. Windsor) plants grown at 20 and 5 degrees C.
      Proton uptake by warm-grown thylakoids was sensitive to external pH and
      stimulated by micromolar adenine nucleotide above pH 7.0. Electron transport was
      modulated by pH, adenine nucleotide and energy transfer inhibitors (triphenyltin
      and Hg(2+) ). By contrast, proton uptake by cold-grown thylakoids was generally
      lower and was insensitive to micromolar ATP. The rate of non-phosphorylating
      electron flow in cold-grown thylakoids was relatively insensitive to pH and
      Hg(2+) and was not modulated by adenine nucleotides or triphenyltin. Stimulation
      of electron transport by phosphorylating conditions in cold-grown thylakoids was
      generally lower and insensitive to pH. It is concluded that the control of proton
      efflux through CF(0) -CF(1) differs in thylakoids of V. faba grown at warm and
      cold temperatures.

PMID- 21087275
TI  - [(14) C]-Assimilate translocation in the light and dark in celery (Apium
      graveokns) leaves of different ages.
AB  - The 2 major photosynthetic products and translocated carbohydrates in celery
      (Apium graveolens L.) are sucrose and the sugar alcohol, mannitol. Sucrose is
      produced and utilized in leaves of all ages. Mannitol, however, is synthesized
      primarily in mature leaves, utilized in young leaves and stored in all leaves.
      Here we show that mannitol export was lower from young, expanding leaves than
      from older leaves. After a 10 min pulse of (14) CO(2) and a 2 h chase in the
      light or dark there was more radioactivity in sucrose than in mannitol in petiole
      tissues from leaves of all ages. However, after a chase of 15 h in the dark or 6
      h in the light followed by 9 h in the dark, mannitol was the predominant [(14) C]
      labeled carbohydrate remaining in all leaf and petiole tissues. Thus, newly
      synthesized sucrose was apparently exported at a faster rate than mannitol and
      more mannitol was partitioned into vacuolar storage pools than was sucrose. It
      also appears that in the light both sucrose and mannitol were exported, but in
      the dark, once sucrose pools were depleted, mannitol remained as the predominant
      substance translocated. Both mannitol and sucrose were unloaded into petiole
      storage parenchyma tissue, but sucrose was hydrolyzed prior to storage.

PMID- 21087276
TI  - The relationship between phosphate status and cyanide-resistant respiration in
      bean roots.
AB  - Bean (Phaseolus vulgaris L.) seedlings were cultured on complete or phosphate
      deficient nutrient medium. After 14 days of culture on phosphate-deficient medium
      the visible symptoms of P(i) deficiency were observed only in the shoot, the
      fresh and dry weights of the roots were slightly higher than in control plants.
      The decreased P(i) content in the roots had little effect on total respiration
      rate but had an effect on the level of inhibition of respiration by cyanide. The
      high resistance of respiration to cyanide observed in P(i) -deficient roots was
      the result of the suppression of cytochrome path activity and an increased
      participation of the alternative, cyanide-resistant pathway. The cytochrome
      pathway activity increased when inorganic phosphate was supplied to P(i) 
      deficient roots for 1 or 3.5 h. It is speculated that the suppression of
      cytochrome pathway in P(i) -deficient roots may result from restriction of the
      phosphorylating capacity or a partial inhibition of cytochrome oxidase activity.

PMID- 21087277
TI  - Photomorphogenic responses to UV radiation: Involvement of phytochrome and UV
      photoreceptors in the control of hypocotyl elongation in Lycopersicon esculentum.
AB  - The photo-inhibition of Lycopersicon esculentum Mill, hypocotyl growth induced by
      UV radiation may be mediated by both phytochrome and UV-absorbing receptors. The
      inhibition of growth induced by continuous irradiation with high fluence rate UV
      radiation is similar in the au mutant, which is severely deficient in
      spectrophoto metrically and immunochemically detectable phytochrome, and in the
      isogenic wild type. Parallel irradiation with 692 nm light, which is equivalent
      to UV radiation for the phytochrome system in our experimental conditions,
      induced at high photon fluence rates a significant increase in hypocotyl growth
      in the au mutant. The same light treatments inhibited the hypocotyl growth of the
      wild type. The responses of water-grown seedlings and chlorophyll-free seedlings
      (streptomycin and norflurazon treated seedlings) were compared. Water-grown and
      chlorophyll-free seedlings responded similarly to UV radiation. The presence of
      chlorophyll correlates with a significant increase in hypocotyl growth of au
      mutants irradiated with 692 nm light. These results support the conclusion that
      UV-induced inhibition of growth in the au mutant is independent of phytochrome.

PMID- 21087278
TI  - Growth and development of Brassica genotypes differing in endogenous gibberellin
      content. I. Leaf and reproductive development.
AB  - Leaf and reproductive development were compared in 3 rapid cycling Brassica rapa
      genotypes grown for 4 weeks under greenhouse conditions. The dwarf mutant,
      rosette (ros), is gibberellin (GA)-deficient, while the tall mutant, elongated
      internode (ein), has enhanced endogenous GA levels. Germination was delayed in
      ros and a selection of a more severe form of ros, named dormant (do), has even
      more retarded germination and some seeds entirely fail to germinate. Seeds of do
      and ros respond to exogenous GA, by rapid germination. The 3 genotypes, ros,
      normal and ein, displayed similar developmental sequences, although floral bud
      formation and subsequent floral development and anthesis were delayed in ros.
      Conversely, anthesis was slightly accelerated in ein. Individual leaf areas were
      reduced in both ros and ein relative to the normal genotype, but leaf numbers
      were similar in all 3 genotypes. Differences in leaf morphology (heterophylly)
      were also observed; the normal genotype and ein plants possessed uniform leaf
      shapes and relatively smooth leaf margins, although petiole length was increased
      in ein. The mutant ros had scalloped leaf margins and convoluted leaf blades in
      addition to shortened petioles. These phenotypes suggest a role for GA in the
      regulation of germination and reproductive and leaf development in Brassica.

PMID- 21087279
TI  - Growth and development of Brassica genotypes differing in endogenous gibberellin
      content. II. Gibberellin content, growth analyses and cell size.
AB  - Three rapid cycling Brassica rapa genotypes were grown in greenhouse conditions
      to investigate the possible relationships between endogenous gibberellin (GA)
      content and shoot growth. Endogenous GA(1) GA(3) and GA(20) were extracted from
      stem samples harvested at 3 weekly intervals and analyzed by gas chromatography
      mass spectrometry with selected ion monitoring, using [(2) H(2) ]-GA(1) and [(2)
      H(2) ]-GA(20) as quantitative internal standards. During the first 2 weeks, GA
      levels of the dwarf, rosette (ros), averaged 36% of levels in normal plants (on a
      per stem basis). Levels in the tall mutant, elongated internode (ein), were
      consistently higher, averaging 305% of levels in normal plants. Differences in
      shoot height across the genotypes resulted from varying internode length which
      resulted from epidermal cell length and number being increased in ein and
      decreased in ros relative to the normal genotype. The exogenous application of
      GA(3) to normal plants increased cell length while the application of
      paclobutrazol (PP333), a triazole plant growth retardant, reduced cell size.
      Thus, exogenous GA manipulations mimicked the influence of the mutant genes ros
      and ein. The dwarf, ros, had reduced shoot dry weights and relative growth rates
      compared to the other genotypes. Total dry weights were similar in ein and the
      normal genotype but stem weights were increased in ein, compensating for
      decreased leaf weights. Thus, the gibberellin-deficiency of ros resulted in
      generally reduced shoot growth. The overproduction of endogenous GA by ein did
      not result in enhanced shoot growth but rather a specific enhancement of
      internode elongation and stem growth at the expense of leaf size.

PMID- 21087280
TI  - Influx and efflux of K(+) in sunflower roots after transfer between solutions
      with different K(+) concentrations.
AB  - It was investigated whether K(+) efflux, like K(+) influx, is affected when roots
      are transferred between solutions with different K(+) concentrations. Sunflower
      plants (Hehanthus annuus L. cv. Uniflorus) were grown on complete nutrient
      solutions with 0.1, 1.0, 10 or 25 mM K(+) . This produced plants with K(+)
      concentrations in the roots varying between 9 and 110 MUmol (g fresh weight)(-1)
      . At the beginning of the experiments the plants were transferred to an (86) Rb
      labelled experimental solution initially containing 0.1 mM K(+) . At intervals
      during 6.5 h samples were removed from the solution and analyzed for K(+) and
      radioactivity. Based on the analyses K(+) ((86) Rb) influx, K(+) net uptake and
      K(+) efflux could be computed. In'low K(+) 'roots, K(+) ((86) Rb) influx and K(+)
      net uptake agreed, suggesting a very low K(+) efflux. This was contrary to'high
      K(+) 'roots, where K(+) efflux was initially higher than K(+) ((86) Rb) influx.
      After about 4 h, K(+) efflux declined to a low value also in these roots. When 2
      4-dinitrophenol was included in the experimental solution, K(+) ((86) Rb) influx
      was generally depressed, whereas K(+) efflux was high throughout the experiment
      and directly proportional to the K(+) status of the roots. Our hypothesis is that
      after transfer of'high K(+) 'roots to a solution with low K(+) concentration, the
      K(+) efflux from the vacuoles of root cells transiently increases, until a new
      electrochemical equilibrium is attained.

PMID- 21087281
TI  - Direct isolation of vacuoles from leaf tissue of lettuce (Lactuca sativa)
      retaining protoplasts within the leaves.
AB  - A procedure is described in which vacuoles are isolated from leaf tissue of
      lettuce (Lactuca sativa L.). After incubation in an enzyme solution, the vacuoles
      are directly extracted from the leaf tissue by osmotic shock using a phosphate
      buffer. In this method no protoplasts are released from the leaf tissue. This
      procedure avoids the problems of separating vacuoles from protoplasts with
      similar density. To evaluate the purity of the vacuoles, the activity of glucan
      synthetase 11 (EC 2.4.1.34), NAD(P) H-cytochrome c reductase (EC 1.6.99.3) and
      malate dehydrogenase (EC 1.1.1.37) was measured. To measure vanadate- and nitrate
      sensitive ATPase activity (EC 3.6.1.8) vesicles were prepared from the vacuoles
      and ATP-dependent vesicle acidification was measured as acridine orange
      quenching. Nitrate inhibited the quenching, while addition of vanadate had no
      effect. It was concluded that the vacuoles were not contaminated with plasma
      membranes. To evaluate the viability of the vacuoles [(14) C]-malate uptake was
      measured. The vacuoles showed a constant rate of [(14) C]-malate uptake during 45
      min. This rate was maximal at pH 6.8.

PMID- 21087282
TI  - A new theory of phototropism - its regulation by a light-induced gradient of
      auxin-inhibiting substances.
AB  - Against the wholly indirect evidence of a lateral gradient of auxin as an
      explanation of phototropic curvature according to the Cholodny-Went theory,
      direct measurement of free. extractable or diffusable indoleacetic acid from
      phototropically curving hypocotyls and coleoptiles invariably shows an even
      distribution of auxin. On the contrary, growth inhibitors extracted or diffused
      from these organs turn out to be accumulated at the irradiated side, as proposed
      already by A. H. Blaauw (Z. Bot. 7: 465. 1915). the classical experiment by F. W.
      Went (Rec. Trav. Bot. Neerl. 25:1, 1928) has to be interpreted as evidence for a
      lateral gradient of substance(s) inhibiting auxin activity Phototropic curvature
      is thus a matter of differential auxin sensitivity across the unilaterally
      irradiated organ.

PMID- 21087283
TI  - Potassium ion channels in the plasmalemma.
AB  - The potassium ion is an indispensible cytosolic component of living cells and a
      key osmolyte of plant cells, crossing the plasmalemma to drive physiological
      processes like cell growth and motor cell activity. K(+) transport across the
      plasmalemma may be passive through channels, driven by the electrochemical
      gradient, K(+) equilibrium potential (E(K) ) - membrane potential (V(m) ), or
      secondary active by coupling through a carrier to the inward driving force of
      H(+) or Na(+) . Known K(+) channels are permeable to monovalent cations, a
      permeability order being K(+) > Rb(+) > NH(4) (+) > Na(+) >= Li(+) > Cs(+) . The
      macroscopic K(+) currents across a cell or protoplast surface commonly show
      rectification, i.e. a V(m) -dependent conductance which in turn, may be
      controlled by the cytosolic activity of Ca(2+) , of K(+) , of H(+) , or by the
      K(+) driving force. Analysis by the patch clamp technique reveals that plant K(+)
      channels are similar to animal channels in their single channel conductance (4 to
      100 pS), but different in that a given channel population slowly activates and
      may not inactivate at all. Single-channel kinetics reveal a broad range of open
      times (ms to s) and closed times (up to 100 s). Further progress in elucidating
      plant K(+) channels will critically depend on molecular cloning, and the
      availability of channel-specific (phyto)toxins.

PMID- 21087284
TI  - Utilization of blood transfusion among older adults in the United States.
AB  - BACKGROUND: While there have been epidemiologic studies of blood donors, the
      characteristics of individuals who receive transfusions have not been well
      described for the US population. STUDY DESIGN AND METHODS: Subjects were from the
      nationally representative Health and Retirement Study whose data were linked to
      Medicare files from 1991 through 2007 (n = 16,377). A cohort study was conducted
      to assess the frequency of transfusion in older Americans over time and to
      describe the characteristics of blood recipients. RESULTS: Thirty-one percent
      (95% confidence interval [CI], 30%-33%) of older Americans received at least one
      transfusion within a 10-year period and 5.8% (95% CI, 5.4%-6.2%) experienced
      repeated transfusion-related visits within 30 days. The mean number of
      transfusion-related visits was 2.3 over a 10-year period (95% CI, 2.2-2.4). Older
      Americans who lived in the South were most likely to receive a transfusion (34%),
      independent of demographic and health-related factors, while those who lived in
      the western United States were the least likely (26%). Predictors of transfusion
      included smoking, low body mass index, and a history of cancer, diabetes
      mellitus, end-stage renal disease, and heart disease. African-Americans and
      Mexican-Americans had greater rates of blood utilization than other races and
      other Hispanics (respectively). There were also differences in transfusion
      utilization by education, marital status, religion, and alcohol use. CONCLUSIONS:
      Transfusion is common in older Americans. Regional variations in blood use are
      not explained by patient characteristics alone.

PMID- 21087286
TI  - A cluster of human immunodeficiency virus Type 1 recombinant form escaping
      detection by commercial genomic amplification assays.
AB  - BACKGROUND: Nucleic acid testing (NAT)-based methods for the detection and
      quantification of human immunodeficiency virus Type 1 (HIV-1) RNA are used to
      increase transfusion safety and to diagnose and manage HIV-1-infected patients.
      We describe a novel HIV-1 recombinant form associated with lack of reactivity or
      substantial underestimation of viral load by commercial NAT assays. STUDY DESIGN
      AND METHODS: We observed a repeat blood donor seroconverting to anti-HIV in whom
      HIV RNA was initially undetectable with routine NAT was observed. During donor
      follow-up, HIV RNA became detectable, but the viral load was 2 to 3 log lower
      than measured with other NATs targeting different genome regions. Genome
      sequencing revealed a novel B/F recombinant with mutations affecting primers and
      probe annealing accounting for the poor performance of routine NAT. A total of
      553 HIV-1-infected patients attending the hospital clinic were subsequently
      tested prospectively using the routine assay and an in-house assay specifically
      designed to detect the B/F strains. RESULTS: The routine assay substantially
      underestimated viremia (1-5 log) in 19 cases (3.5%), 11 (58%) of which were
      infected with the same B/F strain observed in the index donor samples. Two other
      non-B circulating recombinant forms of HIV-1 (A/G, B/G subtypes) were identified
      as poorly detected. Newly introduced NATs targeting two HIV-1 regions improved
      assay performance. CONCLUSION: HIV-1 increasing heterogeneity affects the
      efficiency of NATs and consequently the safety of the blood supply as well as
      diagnosis and patient management.

PMID- 21087285
TI  - Agreement among HLA antibody detection assays is higher in ever-pregnant donors
      and improved using a consensus cutoff.
AB  - BACKGROUND: HLA antibodies might contribute to the pathogenesis of transfusion
      related acute lung injury (TRALI). HLA antibody detection methods include ELISA,
      flow cytometry, and multiplex bead-based assays, as well as the older
      lymphocytotoxicity assay, and it is not obvious how to compare results across
      platforms. STUDY DESIGN AND METHODS: Five hundred twenty-five serum samples were
      selected from 7841 donors in the Leukocyte Antibody Prevalence Study (LAPS)
      repository based on risk for the development of HLA antibodies, using the number
      of pregnancies as the risk factor. Subjects included 81 males and females with 0
      (n = 187), 1 (n = 67), or 2+ pregnancies (n = 190). Replicate frozen serum
      aliquots were sent blinded to four different HLA antibody assay manufacturers for
      detection using five different assays. RESULTS: The flow cytometry and multiplex
      bead based-assays typically resulted in a larger proportion of HLA antibody
      positive samples compared with ELISA based assays. Latent variable analysis was
      used to derive a new set of consensus cutoffs, which yielded similar
      sensitivities across test platforms and increased concordance amongst assays.
      Assay agreement was higher in ever pregnant females than in males and never
      pregnant females. CONCLUSIONS: Different assays resulted in varied positivity
      rates when the manufacturer's suggested cutoffs were used, demonstrating that
      care needs to be taken when comparing clinical outcomes data generated using
      different HLA antibody assays and testing platforms. The method used here,
      involving latent variable analysis, presents one possible approach to calculating
      comparable cutoffs that result in broad agreement across assays with respect to
      positivity designation.

PMID- 21087287
TI  - Liver iron overloading in captive muriquis (Brachyteles spp.).
AB  - BACKGROUND: Iron accumulation was investigated qualitatively and quantitatively
      in the liver of 15 captive Brachyteles spp. METHODS: Hepatic hemosiderosis index
      (HHI) was determined as the area percentage of the liver parenchyma occupied by
      hemosiderin and ferritin deposits, through computerized histomorphometric
      analysis of Prussian blue-stained histologic sections. RESULTS: All studied
      animals presented liver hemosiderosis, and HHI ranged from 0.2% to 41.7%. There
      were no significant differences in HHI between muriqui species or genders, and no
      correlations were detected among HHI and age, time in captivity or body mass.
      Iron deposits were accompanied by other hepatic disorders. CONCLUSIONS: This is
      the first study addressing the occurrence and consequences of iron overloading in
      the liver of muriquis. We propose that hemosiderosis may act as a contribute
      factor for the development of hepatic injuries. Further studies are advised to
      clarify the role of diet in the pathogenesis of hemosiderosis in these atelids.

PMID- 21087288
TI  - A placebo-controlled, randomized clinical trial using testosterone undecanoate
      with injectable norethisterone enanthate: effect on anthropometric, metabolic and
      biochemical parameters.
AB  - Testosterone administered alone or in combination with progestogens in male
      contraception induces reversible oligo-azoospermia, but its effects on body
      composition and metabolism are less known. We analysed anthropometric and
      metabolic parameters in five groups of 10 males: four receiving testosterone
      undecanoate (TU: 1000 mg) plus norethisterone enanthate (NETE: 200 mg) at
      different intervals (every 8 weeks: NETE-8; every 12 weeks: NETE-12; every 6
      weeks for 12 weeks and then every 12 weeks: NETE-6/12; every 6 weeks for 12 weeks
      and then TU plus placebo every 12 weeks: NETE-6/12/0) and one placebo (NETE-0/0)
      for a total of 48 weeks. Body mass index (BMI) and waist circumference did not
      change in any groups except for the NETE-8 in which BMI increased significantly
      (p = 0.02) at the end of the treatment period. Lean body mass (MAMC or AMA)
      increased significantly in the highest hormonal dose groups (p = 0.04, NETE-6/12;
      p = 0.004, NETE-8). No differences were observed in glucose levels, insulin
      sensitivity index and lipid profile as well as in biochemical and cell count
      parameters in any groups. In conclusion, NETE and TU for 48 weeks were not
      accompanied by any metabolic changes and any adverse effects. The weight gain of
      the highest NETE plus TU dosage was mainly because of gain in muscle mass.

PMID- 21087289
TI  - The importance of glucocorticoids in alcohol dependence and neurotoxicity.
AB  - Alterations in hypothalamo-pituitary adrenal (HPA) function have been described
      in alcoholics and in rodents after chronic alcohol consumption but the role of
      glucocorticoids in alcohol consumption, and the mechanisms involved, has received
      little attention until recently. Both alcohol consumption and withdrawal from
      chronic alcohol intake raise circulating glucocorticoid levels, and prolonged
      high concentrations of glucocorticoids are known to have detrimental effects on
      neuronal function and cognition. This minireview covers the ways in which
      glucocorticoids may be involved in drinking behavior, from social drinking to
      dependence, and the negative consequences of alcohol consumption seen during
      withdrawal which may have a detrimental effect on treatment outcome. Research
      shows prolonged increases in brain glucocorticoid concentrations and decreased
      brain glucocorticoid receptor availability (consistent with increased levels of
      endogenous ligand) after withdrawal from chronic alcohol treatment. Evidence
      suggests that increased glucocorticoid levels in the brain after chronic alcohol
      treatment are associated with the cognitive deficits seen during abstinence which
      impact on treatment efficacy and quality of life. Studies on organotypic cultures
      also demonstrate the importance of glucocorticoids in the neuropathological
      consequences of alcohol dependence.

PMID- 21087291
TI  - Decision-making in people who relapsed to driving under the influence of alcohol.
AB  - BACKGROUND: Alcohol use has been previously associated with neurocognitive
      impairments, especially in decision-making cognition. However, some studies have
      shown little to no decision-making deficits in relation to different
      characteristics of people with drinking problems. Relapsing to driving under the
      influence (DUI) of alcohol is an important issue with legal and psychosocial
      aspects. We evaluated decision-making performance in second-time DUI offenders by
      using the Iowa Gambling Task (IGT). METHOD: Thirty-four male second-time DUI
      offenders who had been selected for an official psychoeducational rehabilitation
      program and 31 healthy controls that were matched for age, education, and alcohol
      use were included. Along with psychiatric assessment, we applied conventional
      neuropsychological testing comprising cognitive set-shifting, response
      inhibition, attention, and visuospatial abilities. Also, we used the Temperament
      and Character Inventory (TCI) to assess personality patterns. A computerized
      version of IGT was used. RESULTS: No significant differences were found between
      the groups in regard to sociodemographics and conventional neuropsychological
      testing. DUI participants had significantly higher scores only in "self
      transcendence" subdomain of TCI. On the fifth block of the IGT, DUI participants
      had significantly lower net scores than controls (U = 380.0, p < 0.05). Also, DUI
      participants chose significantly more risky decks compared to controls.
      CONCLUSIONS: Our results suggest that there may be subtle decision-making
      deficits in DUI participants, which goes undetected on conventional
      neuropsychological testing and which is not correlated with TCI subdomains
      related with impulsivity patterns.

PMID- 21087290
TI  - Body mass index is associated with brain metabolite levels in alcohol dependence-
      a multimodal magnetic resonance study.
AB  - BACKGROUND: Recent studies demonstrated that alcohol dependence and excessive
      alcohol consumption are associated with increased rates of obesity. In healthy
      light-drinkers, we and others have observed associations between elevated body
      mass index (BMI) and reductions in brain volumes, lower concentrations of N
      acetyl-aspartate (NAA, marker of neuronal viability) and choline-containing
      compounds (Cho, involved in membrane turnover), and lower glucose utilization,
      particularly in frontal lobe-a brain region that is particularly vulnerable to
      the effects of alcohol dependence. Here, we evaluated whether BMI in alcohol
      dependent individuals was independently associated with regional measures of
      brain structure, metabolite concentrations, and neocortical blood flow. METHODS:
      As part of a study on the effects of alcohol dependence on neurobiology, we
      analyzed retrospectively data from 54 alcohol-dependent males, abstinent from
      alcohol for about 1 month and with BMI between 20 and 37 kg/m(2) by structural
      MRI, perfusion MRI (blood flow), and proton magnetic resonance spectroscopic
      imaging. RESULTS: After correction for age, smoking status, and various measures
      of alcohol consumption, higher BMI was associated with lower concentrations of
      NAA, Cho, creatine and phosphocreatine (Cr, involved in high energy metabolism),
      and myo-inositol (m-Ino, a putative marker of astrocytes) primarily in the
      frontal lobe, in subcortical nuclei, and cerebellar vermis (p < 0.004). Regional
      brain volumes and perfusion were not significantly related to BMI. Furthermore,
      comorbid conditions, clinical laboratory measures, and nutritional assessments
      were not significant predictors of these MR-based measures. CONCLUSIONS: The
      results suggest that BMI, independent of age, alcohol consumption, and common
      comorbidities, is related to regional NAA, Cho, Cr, and m-Ino concentrations in
      this cohort of alcohol-dependent individuals. Additionally, as some common
      comorbid conditions in alcohol dependence such as cigarette smoking are
      associated with BMI, their associations with regional brain metabolite levels in
      alcohol-dependent individuals may also be influenced by BMI.

PMID- 21087292
TI  - Intraprocedural imaging of left atrium and pulmonary veins: a comparison study
      between rotational angiography and cardiac computed tomography.
AB  - BACKGROUND: Atrial fibrillation (AF) ablation is facilitated by anatomical
      visualization of the left atrium (LA) and the pulmonary veins (PVs). The purpose
      of this study was to compare accuracy, radiation exposure, and costs between
      three-dimensional atriography (3D-ATG) and cardiac computed tomography (CCT).
      METHODS: Seventy patients with an indication for AF ablation were included.
      Contrast-enhanced CCT was performed preoperatively for all patients. In addition,
      intraoperative 3D-ATG was performed with contrast medium injection either
      indirectly into the pulmonary arteries during a breath-hold (Ind.-RTA, n = 25) or
      directly into the LA, during adenosine-induced asystole (Ad.-RTA, n = 23), or
      rapid ventricular pacing (VP-RTA, n = 22). We evaluated vertical ostial PV
      diameters and LA volume, time needed to perform, radiation exposure, and
      procedural cost for each imaging method. RESULTS: The correlation coefficient
      between 3D-ATG and CCT for the ostial PV diameters was r = 0.83 for Ind.-RTA,
      0.91 for Ad.-RTA, and 0.88 for the VP-RTA method (P > 0.05). The volume
      correlations were r = 0.87 for Ind.-RTA, 0.82 for Ad.-RTA, and 0.8 for VP-RTA (P
      > 0.05). Time to perform was 13 +/- 5 minutes for ATG and 46 +/- 9 minutes for
      CCT (P < 0.05). Effective radiation dose was 2.2 +/- 0.2 mSv for ATG and 20.4 +/-
      7.4 mSv for CCT (P < 0.05). The procedural cost was estimated at 91-95 ? for ATG
      and at 126-151 ? for CCT. CONCLUSIONS: 3D-ATG is an intraprocedural imaging
      modality that provides anatomical accuracy comparable to that of CCT with
      significantly lower radiation dose, in less time and at less financial expense
      (PACE 2011; 34:315-322).

PMID- 21087293
TI  - Mental health and sense of coherence among Swedish adults with cystic fibrosis.
AB  - The purpose of this study was to describe mental health among adult Swedish
      patients with cystic fibrosis (CF) and to study if mental health and the
      salutogene factor sense of coherence (SOC) intercorrelate with good medical
      status. Women and men were compared. The patient group (n=59) attended the
      Stockholm CF Center. Mental health was measured with the General Health
      Questionnaire (GHQ-28) and the salutogenesis by SOC-3. Medical status included
      forced vital capacity and forced expiratory volume in 1 second in per cent of
      predicted as well as Body Mass Index. The differences within and between groups
      were tested with t-tests and the relations between the variables were described
      by Spearman's correlation coefficient. The patients had on the whole good mental
      health, but the group with a risk of mental ill-health (n=19) experienced life as
      difficult to manage, meaningless and hard to understand compared to the group
      with a small risk of mental ill-health (n=40). Women at risk of mental ill-health
      (n=10) experienced difficulties in managing life to a greater extent than women
      with a small risk of mental ill-health (n=16). Men at risk of mental ill-health
      (n=9) found life hard to understand. Mental health and SOC did not correlate
      significantly with the medical status of the CF patients. The conclusion was that
      there were comparably few problems of mental health among the patients with CF.
      The problems that were found were not related to the seriousness of their CF.
      Women had a more complex pattern of problems in mental health and SOC than men
      had.

PMID- 21087294
TI  - Immediate non-occlusal loading of single implants in the aesthetic zone: a
      randomized clinical trial.
AB  - AIM: this study compared the outcome of immediate non-occlusal loading with
      conventional loading for single implants in the maxillary aesthetic zone. It was
      hypothesized that immediate non-occlusal loading is not inferior to conventional
      loading. MATERIALS AND METHODS: sixty-two patients with a missing maxillary
      anterior tooth were randomly assigned to be treated with an implant that was
      either restored with a non-occluding temporary crown within 24 h after implant
      placement (the "immediate group") or was restored according to a two-stage
      procedure after 3 months (the "conventional group"). All implants were installed
      in healed sites. Follow-up visits were conducted after 6 and 18 months post
      implant placement. Outcome measures were radiographic marginal bone-level
      changes, survival, soft tissue aspects (probing depth, plaque, bleeding, soft
      tissue level), aesthetics and patient satisfaction. RESULTS: no significant
      differences were found between both study groups regarding marginal bone loss
      (immediate group 0.91 +/- 0.61 mm, conventional group 0.90 +/- 0.57 mm), survival
      (immediate group 96.8%: one implant lost, conventional group 100%), soft tissue
      aspects, aesthetic outcome and patient satisfaction. CONCLUSION: within the
      limitations of this study (sample size, follow-up duration), it was demonstrated
      that, for single implants in the anterior maxilla, the outcome of immediate non
      occlusal loading was not less favourable than conventional loading.

PMID- 21087295
TI  - What is the right dose for children?

PMID- 21087296
TI  - Identification and differentiation of Cryptosporidium species by capillary
      electrophoresis single-strand conformation polymorphism.
AB  - Cryptosporidium species generally lack distinguishing morphological traits, and
      consequently, molecular methods are commonly used for parasite identification.
      Various methods for Cryptosporidium identification have been proposed, each with
      their advantages and disadvantages. In this study, we show that capillary
      electrophoresis coupled with single-strand conformation polymorphism (CE-SSCP) is
      a rapid, simple and cost-effective method for the identification of
      Cryptosporidium species and genotypes. Species could be readily differentiated
      based on the SSCP mobility of amplified 18S rRNA gene molecules. Clones that
      differed by single-nucleotide polymorphisms could be distinguished on CE-SSCP
      mobility. Profiles of species known to have heterogenic copies of 18S rRNA gene
      contained multiple peaks. Cloning and sequencing of Cryptosporidium parvum,
      Cryptosporidium hominis, Cryptosporidium fayeri and Cryptosporidium possum
      genotype 18S rRNA gene amplicons confirmed that these multiple peaks represented
      type A and type B 18S rRNA gene copies. CE-SSCP provides a reliable and sensitive
      analysis for epidemiological studies, environmental detection and diversity
      screening.

PMID- 21087297
TI  - Metabolism of organochlorine pesticide heptachlor and its metabolite heptachlor
      epoxide by white rot fungi, belonging to genus Phlebia.
AB  - White rot fungi of the genus Phlebia have demonstrated a high capacity to degrade
      organic pollutants, including polychlorinated dibenzo-p-dioxins and
      polychlorinated biphenyls. In this study, we evaluated the ability of 18 white
      rot fungi species of genus Phlebia to degrade heptachlor and heptachlor epoxide,
      and described the metabolic pathways by selected white rot fungi. Phlebia
      tremellosa, Phlebia brevispora and Phlebia acanthocystis removed about 71%, 74%
      and 90% of heptachlor, respectively, after 14 days of incubation. A large amount
      of heptachlor epoxide and a small amount of 1-hydroxychlordene and 1-hydroxy-2,3
      epoxychlordene were detected as metabolic products of heptachlor from most fungal
      cultures. The screening of heptachlor epoxide-degrading fungi revealed that
      several fungi are capable of degrading heptachlor epoxide, which is a
      recalcitrant metabolite of heptachlor. Phlebia acanthocystis, P. brevispora,
      Phlebia lindtneri and Phlebia aurea removed about 16%, 16%, 22% and 25% of
      heptachlor epoxide, respectively, after 14 days of incubation. Heptachlor diol
      and 1-hydroxy-2,3-epoxychlordene were produced in these fungal cultures as
      metabolites, suggesting that the hydrolysis and hydroxylation reaction occur in
      the epoxide ring and in position 1 of heptachlor epoxide, respectively.

PMID- 21087298
TI  - Nickel allergy: localized, id, and systemic manifestations in children.
AB  - Nickel is the most common allergen causing allergic contact dermatitis in patch
      tested children, especially in female children. Allergy to this metal can
      manifest in a variety of ways. In this case series, we present four children to
      illustrate the different presentations of nickel allergy confirmed by patch
      testing. Localized, id, and systemic nickel reactions are reviewed, as well as
      the diagnosis and management of nickel allergic contact dermatitis. While
      localized dermatitis in areas of direct contact to the allergen is the most
      common and easiest form of nickel allergy to identify, recognition of varying
      presentations is critical as these can result in more chronic and severe
      symptoms, and can be misdiagnosed as atopic dermatitis.

PMID- 21087299
TI  - A primer on the responsibilities and abuses of scientific authorship.

PMID- 21087300
TI  - Condom use and stages of change among college students in Taiwan.
AB  - OBJECTIVES: To explore the correlates for nonuse of condoms and the factors that
      affect stages of change for regular condom use among college students in Taiwan.
      DESIGN AND SAMPLE: Cross-sectional, quantitative survey design. A total of 996
      college students were recruited from two universities in Northern Taiwan.
      MEASURES: Questionnaires collected data on demographic information, condom use,
      HIV/AIDS knowledge, confidence in using condoms in different situations, and
      perceived benefits and barriers to using condoms. RESULTS: The common reasons for
      not using condoms were trust in the partner (21.30%), partner dislike for condoms
      (19.49%), and perception of low risk (18.77%). Most sexually active students
      (52.4%) were in the earliest 2 stages of readiness to change (i.e.,
      precontemplation, contemplation). Participants in action/maintenance were (a)
      43.4% less likely to show a high knowledge score, (b) 4.08 times more likely to
      present high self-efficacy, and (c) 2.24 times more likely to be more religious
      than those in contemplation/preparation. CONCLUSIONS: Among a highly literate
      group, college students, condom use is inconsistent and readiness to change is
      not imminent. This study reveals that preventive steps targeted at young adults
      should address other concerns related to condom use such as trust in partners and
      the alleged appeal of unprotected sex.

PMID- 21087301
TI  - A needs assessment of clients with HIV in a home-based care program in Guyana.
AB  - OBJECTIVE: To assess the needs of clients in a home-based care (HBC) program
      aimed at improving the quality of lives of people living with HIV in Region 4 of
      Guyana (Demerara-Mahaica region) following their involvement with the HBC
      program, volunteers, and nurse providers. DESIGN AND SAMPLE: A cross-sectional
      analysis of a needs assessment conducted through a verbally administered
      questionnaire. We collected a cross-sectional sample of 84 HBC clients living
      with HIV from Region 4 in Guyana. MEASURES: Respondents were administered a
      questionnaire that asked questions regarding the demographics; services received;
      quality of service delivery; and mental health and substance abuse. RESULTS: The
      services most commonly received by respondents included nutritional assessment
      and counseling, HIV prevention education, emotional support, hygiene education,
      support for antiretroviral adherence, and support for HIV disclosure. Respondents
      reported further need of referrals to income-generation opportunities, food and
      nutritional supplement support, and support for children. Forty-two percent of
      the respondents screened positive for probable depression, and 37% of respondents
      screened positive for being at risk for a drinking problem. CONCLUSIONS: While a
      substantial portion of needs were addressed by the HBC program, outstanding needs
      included linking people living with HIV to income-generation opportunities, food
      support, mental health, and services for children. We suggest that mental health
      and substance use services be factored into HIV programming and that referral
      systems be strengthened to ensure access to support services for people living
      with HIV.

PMID- 21087303
TI  - Perceived barriers to prostate cancer screenings among middle-aged men in north
      eastern Germany.
AB  - OBJECTIVES: Prostate cancer ranks high in mortality. Only 18% of men entitled for
      screenings take advantage of this. Social-cognitive models of health psychology
      describe and predict health behavior. This study investigates what barriers men
      perceive that impede the utilization of cancer screenings. DESIGN AND SAMPLE:
      Semistructured interviews were conducted in 2 general practices and 3 hospital
      wards. One hundred and seventy-eight men over 45 years were addressed; 64
      utilized cancer screenings regularly, 3 had a diagnosis of prostate cancer, and
      18 declined participation. MEASURES: Content analyses were conducted with 83
      interviews. The interview tapped into the following domains: barriers, risk
      perception, outcome expectancies, self-efficacy, and intentions. RESULTS: 57 men
      regarded their health as very important, while 47 had never utilized cancer
      screenings. Barriers were divided into emotional/cognitive versus
      organizational/structural. Sixty-four men did not utilize cancer screenings
      because of lack of symptoms, 22 feared a positive result, 20 had more pertinent
      health issues, and 18 assumed that their physicians would screen for cancer
      "automatically." CONCLUSIONS: Mainly emotional/cognitive barriers were seen as
      important for nonutilization, especially the absence of symptoms. Following the
      reasoning of social-cognitive models, a first step to enhance utilization rates
      would be to enhance risk perception.

PMID- 21087302
TI  - Associations of employment frustration with self-rated physical and mental health
      among Asian American immigrants in the U.S. Labor force.
AB  - OBJECTIVE: This study examined the associations between employment frustration
      and both self-rated physical health (SRPH) and self-rated mental health (SRMH)
      among Asian American immigrants. DESIGN AND SAMPLE: A cross-sectional
      quantitative analysis was conducted utilizing data from 1,181 Asian immigrants
      participating in the National Latino and Asian American Study. MEASURES:
      Employment frustration was measured by self-report of having difficulty finding
      the work one wants because of being of Asian descent. SRPH and SRMH were each
      assessed using a global one-item measure, with responses ranging from poor to
      excellent. Control variables included gender, age, ethnicity, education,
      occupation, income, whether immigrated for employment, years in the United
      States, English proficiency, and a general measure for everyday discrimination.
      RESULTS: Ordered logistic regression showed that employment frustration was
      negatively associated with SRPH. This relationship, however, was no longer
      significant in multivariate models including English proficiency. The negative
      association between employment frustration and SRMH persisted even when including
      all control variables. CONCLUSIONS: The findings suggest that Asian immigrants in
      the United States who experience employment frustration report lower levels of
      both physical and mental health. However, English proficiency may attenuate the
      relationship of employment frustration with physical health.

PMID- 21087304
TI  - A volunteer citizen-servant pilot program using tailored messages to empower
      Alabamians to live healthier lives.
AB  - OBJECTIVES: This study examines the use of tailored messages as a learning tool
      to volunteer citizen servants to promote health and empower Alabama citizens to
      live healthier lives. DESIGN AND SAMPLE: Descriptive data of formative and
      summative questionnaires were analyzed from convenience sampling in this study,
      which encompassed 12 months. MEASURES: Researchers formed unique partnerships
      among community service organizations (CSO), faith-based organizations (FBO),
      author affiliated school of nursing, and community organizations to implement
      Healthy People 2010 goals. The program provided "health information stations" to
      focus on delivery of monthly culturally relevant messages to meet the health
      needs in the community. RESULTS: This program provided tailored health messages
      to 11 CSO and FBO. Outcome measures include an increase in health promotion
      knowledge, desire for furtherance and expansion of programs, and improved
      contacts within the community. CONCLUSIONS: The results from this study provide
      achievement of overall program goals, suggestions for improved evaluation
      strategies, implementation plans, and examples of specific topical messages.

PMID- 21087305
TI  - Mammography promotion in the emergency department: a pilot study.
AB  - OBJECTIVES: The objective of this pilot study is to assess the need, desire, and
      applicability of a mammography promotion project in the emergency department
      (ED). DESIGN AND SAMPLE: A convenience sample from the ED of a public University
      hospital was surveyed to determine their mammography status, interest in a
      program to promote mammography, and barriers to mammography. MEASURES: The survey
      included demographics information, health care access, including health insurance
      and primary care provider, mammography status and date of mammogram, as well as a
      checklist of potential barriers. Participants were also asked whether they would
      be interested in mammography promotion in this setting. RESULTS: More than 15% of
      the 197 women surveyed had never received a mammogram, and more than half had not
      received 1 in the past year. The most common barriers to mammography were
      competing demands and money. Three quarters of the women said they would be
      interested in mammography promotion while waiting for care in the ED.
      CONCLUSIONS: This study provides promise that mammography promotion activities
      may be appropriately placed in the ED and provides a solid platform from which
      researchers and nurses may launch efforts to develop preventive health
      interventions in innovative public health care settings.

PMID- 21087306
TI  - Perspectives on healthy behaviors among low-income Latino and non-Latino adults
      in two rural counties.
AB  - OBJECTIVES: Rural populations and individuals with low incomes are less likely
      than the general population to achieve recommended levels of physical activity
      and fruit and vegetable consumption. The purpose of this study was to describe
      the perspectives of low-income adults in 2 rural Wisconsin counties on the
      factors that influence physical activity and healthy eating. DESIGN AND SAMPLE: A
      qualitative descriptive study was conducted using 4 focus groups: 2 in English
      and 2 in Spanish. A convenience sample (N=20) was recruited. MEASURES: Focus
      group questions and data analysis were based on an ecological framework. A team
      of 3 researchers performed content analysis of focus group transcripts. RESULTS:
      Participants reported individual, social, and community influences on health
      behaviors. Individual barriers included lack of motivation and lack of knowledge.
      Participants described the importance of family, friends, and the community
      social climate for health behaviors. Latinos emphasized the need for resources
      such as community gardens and public spaces for physical activity, while non
      Latinos recommended community education related to healthy eating. CONCLUSIONS:
      The results suggest that relevant health promotion strategies in rural, low
      income populations include multilevel approaches, the development of schools as
      health promotion resources, and strategies to build social connections among
      community residents.

PMID- 21087307
TI  - Services delivered by faith-community nurses to individuals with elevated blood
      pressure.
AB  - OBJECTIVE: Our study describes the services faith-community nurses provide to a
      community-dwelling sample of patients with elevated blood pressure. DESIGN AND
      SAMPLE: The faith-community nurses completed a survey describing services
      provided to study participants at each patient encounter. We describe the type of
      contact and the frequency and types of services provided to these patients. From
      October 2006 to October 2007, we conducted a partnered study with a faith
      community nursing program and enrolled 100 adults with elevated blood pressure
      from church health fairs. MEASURES: Patient demographics and faith-community
      nurse services provided. RESULTS: Data from 63 of 108 (58%) visits to faith
      community nurses made by 33 participants were collected from surveys completed by
      the nurses. The majority of the participants were female (64%), Latino (61%),
      with an average age of 59 (SD=11) years and incomes below US$30,000 (83%). The
      most frequent services patients received from faith-community nurses were blood
      pressure measurement (73%), hypertension-specific education on dietary changes
      (67%), and supportive counseling (56%). CONCLUSIONS: Faith-community nurses
      represent a new method of supportive self-management for low-income individuals
      with a chronic condition who may otherwise have limited access to health
      services. Further research is needed to understand the effect of faith-community
      nurse interventions on improving chronic disease health outcomes in these
      communities.

PMID- 21087308
TI  - Training and experience of public health nurses in using behavior change
      counseling.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness,
      feasibility, and usefulness of a behavior change counseling (BCC) training
      program for public health nurses to facilitate behavior change in patients.
      DESIGN AND SAMPLE: This was a quasi-experimental feasibility study. Twelve rural
      public health nurses participated in the study. MEASURES: Nurses participated in
      a 1-day BCC training workshop and 2 follow-up telephone calls within 8 weeks.
      Their pre- and posttraining BCC skills were evaluated based on audio-taped
      interactions using the Behavior Change Counseling Index (BECCI). Additionally,
      interviews were conducted with the nurses to understand their experience with the
      training in the use of BCC in their practice. RESULTS: Descriptive statistics
      demonstrated increased BECCI scores after training. Nurses described the training
      workshop as valuable. Training in BCC helped nurses realize and improve their
      communication skills to facilitate patients' behavior changes. Nurses believed
      that additional training using BCC techniques in typical patient situations would
      help them improve their skill and confidence in using this method. CONCLUSION:
      Nurses found BCC to be a useful tool to facilitate patients' behavioral changes.
      Although training resulted in increased skill in using BCC, nurses felt that they
      needed additional training to master BCC skills.

PMID- 21087309
TI  - Increasing community capacity to reduce tobacco-related health disparities in
      African American communities.
AB  - OBJECTIVE: The purpose of this study was to understand the processes and
      interactions that African American tobacco control organizations use to engage
      African American communities in tobacco control efforts. DESIGN AND SAMPLE: The
      study used grounded theory methods to interpret participant's perspectives on
      tobacco control. The study sample consisted of African American tobacco control
      program directors from African American tobacco control organizations throughout
      the United States. MEASURES: Data collection involved 1 interview per participant
      using a semistructured interview at a location selected by the participant. Each
      interview lasted approximately 30-90 min. RESULTS: The results showed that
      organizations used specific strategies to involve African Americans in tobacco
      control. The tobacco control organizations built community capacity using 3
      processes: developing relationships and partnerships, raising awareness, and
      creating collective power. CONCLUSION: Contextual, cultural processes, and
      historical references used by African American tobacco control organizations
      provide insight into how to engage African American communities in tobacco
      control efforts and achieve tobacco-related health parity. Public health
      professionals and nurses should be aware of these and other strategies that may
      increase the involvement of African American communities in tobacco control.

PMID- 21087310
TI  - Social integration and heath policy issues for international marriage migrant
      women in South Korea.
AB  - Until very recently, Korea was largely considered to be a homogenous, racially
      intolerant country that had little or no experience with large-scale immigration.
      However, this paradigm is in the process of changing. For the first time in the
      country's history, large numbers of foreigners are immigrating to work and live
      in Korea, and many are seeking to become Koreans. In particular, international
      marriage migrations, especially those of women entering the country through
      marriages to Korean men, have become common in South Korea. This has given rise
      to serious challenges within the country. Although conventional ideologies
      portray Korea as a country of a single race, culture, and language, the growing
      number of immigrants has disrupted this homogenous monoculture. Indeed, there are
      signs that Korea has reached a turning point, with an increasingly permanent and
      visible migrant population challenging the country's national identity. This
      article explores the statistics and trends related to international marriage
      migrant women in South Korea, particularly in terms of their social insecurities
      and health-related problems. In addition, some aspects of Korean governmental
      policies for the social integration and health promotion of these women are
      examined, and some suggestions are made for ways in which public health nursing
      and nursing education may be changed in response to the current trends.

PMID- 21087311
TI  - School nursing on the iron range in a public health nursing model.
AB  - Frontier nursing in the public health model might invoke images of school nurses
      on horseback in rural Kentucky or the wilds of the western prairies. Northern
      Minnesota was a frontier in the last decade of the 19th century, due to the
      discovery of one of the richest seams of iron ore on the North American
      continent. Immigrants from Europe responded to the opportunities this discovery
      created. Among the many Finns arriving on the Iron Range of Minnesota, as it came
      to be named, were the parents of Lillian Augusta Wilhelmena Beck, John and Hulda
      Beck. Over her more than nine decades of life, their daughter became one of the
      most well known school nurses on the Iron Range. Her story evokes memories of the
      creation of school nursing in the public health model by nurses at the Henry
      Street Settlement in New York City.

PMID- 21087312
TI  - Beneficial effects of melatonin on obesity and lipid profile in young Zucker
      diabetic fatty rats.
AB  - The study objective was to investigate the effects of melatonin on obesity and
      obesity-associated systolic hypertension and dyslipidemia in young male Zucker
      diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF
      rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean
      and fatty animals were subdivided into three groups (n=10): naive (N), vehicle
      treated (V), and melatonin-treated (M) (10mg/kg/day) for 6wk. Vehicle and
      melatonin were added to the drinking water. Melatonin reduced mean weight gain
      (51+/-2/100g BW) versus N-ZDF group (58+/-3, P<0.05) without food intake
      differences. M-ZDF rats showed an apparent reduction in systolic hypertension
      that proved not to be statistically significant, and a significant improvement in
      dyslipidemia, with a reduction in hypertriglyceridemia from 580+/-40 to 420.6+/
      40.9mg/dL (P<0.01). Melatonin raised high-density-lipoprotein (HDL) cholesterol
      in ZDF (from 81.6+/-4.9 to 103.1+/-4.5mg/dL, P<0.01) and ZL rats (from 62.8+/-4.8
      to 73.5+/-4.8mg/dL, P<0.05) and significantly reduced low-density-lipoprotein
      (LDL) cholesterol in ZDF rats from 5.20+/-0.4 to 4.14+/-0.3 mg/dL (P<0.05) but
      had no effect on total cholesterol levels. To our knowledge, this is the first
      evidence of a positive effect of melatonin on overweight and lipid pattern of
      obese Zucker diabetic rats, supporting the proposition that melatonin
      administration may ameliorate overweight and lipid metabolism in humans. Because
      these benefits occurred in youth, before advanced metabolic and vascular
      complications, melatonin might help to prevent cardiovascular disease associated
      with obesity and dyslipidemia.

PMID- 21087313
TI  - Analysis of nonsexual injuries of the male genitals in children and adolescents.
AB  - AIM: This study analysed nonsexual male genital injuries in boys with regards to
      aetiology, age, management and outcome. METHODS: Patients were identified from
      the hospital database (between 1999 and 2009) were analysed retrospectively.
      RESULTS: Seventy-four patients (2-17 years) were identified which included 24
      toddlers and small children (2-5 years), 36 school age children (6-12 years) and
      14 adolescents (13-17 years). Traumas were related to falls (n=14), kicks (n=11),
      sport (n=10), toilet seats (n=9), motor vehicles (n=8), bicycle (n=4), outdoor
      activities (n=4) and others causes (n=14). The leading cause of injuries in (i)
      toddler and small children was related to toilet seat (n=7) and falls (n=7), (ii)
      school age children to sport (n=8), kicks (n=7) and falls (n=6), and (iii)
      adolescents to motorcycle accidents (n=5). There were 45 scrotal and 29 penile
      injuries ranging from lacerations to contusions. Sixty-eight patients required
      hospital stay (0.5-36 days, Sigma=2.4 days). Follow-up examinations were
      uneventful, except for one minor wound infection. CONCLUSION: Nonsexual traumas
      to the male external genitalia occur mostly in 6- to 12-year-old boys, with sport
      accidents, kicks and falls being the major causes. Scrotal and penile lacerations
      and testicular contusions are the most common injuries. Complications after
      injuries to the male genitals in children are rare.

PMID- 21087314
TI  - Implant-supported fixed prostheses in the edentulous maxilla: 8-year prospective
      results.
AB  - OBJECTIVE: The purpose of this prospective study was to evaluate the long-term
      survival and success rates of implants and screw-retained, full-arch prostheses
      placed in edentulous maxillae over 8 years of function. MATERIALS AND METHODS: A
      total of 106 Astra Tech implants were placed in the maxillae of 17 edentulous
      patients in a one-stage surgical approach. After a healing period of 6 months,
      the patients received fixed screw-retained bridges. Follow-up visits, including
      clinical and radiographic examinations, were performed after 6 months and at
      yearly intervals. Implant survival, implant success, and marginal bone-level
      changes were defined as the primary outcome variables. The secondary aims were to
      report periodontal pathogens at 5 years' follow-up and patients' satisfaction at
      the 8-year follow-up. RESULTS: The overall observation time was 8 years. One
      patient died during the study and one implant failed during the healing period,
      yielding an 8-year cumulative implant survival rate of 99%. The prosthetic
      survival rate was 100%. The mean crestal bone loss amounted to 0.3 +/- 0.72 mm.
      Patients' subjective evaluations demonstrated an overall high level of
      satisfaction. In all cases, except for one, microbiologic probing of the peri
      implant sulcus after 5 years showed no higher incidence of periodontal pathogens.
      CONCLUSIONS: Screw-retained, full-arch restorations on six implants in an
      edentulous maxilla are a predictable and highly successful treatment concept as
      observed throughout this study with an observation period of 8 years of function,
      in particular with respect to low crestal bone loss and high patient
      satisfaction.

PMID- 21087315
TI  - Apical and marginal bone alterations around implants in maxillary sinus
      augmentation grafted with autogenous bone or bovine bone material and
      simultaneous or delayed dental implant positioning.
AB  - OBJECTIVE: A re-pneumatization phenomenon was recorded in sinuses grafted with
      different materials. The specific aims of this paper were to assess the dental
      implant survival rate and the behavior of marginal and apical bone remodeling
      around dental implants placed following sinus augmentation. MATERIALS AND
      METHODS: A retrospective study was conducted on consecutive patients treated in
      two surgical centers. Different surgical techniques were adopted for sinus
      augmentation: simultaneous or delayed dental implant insertion with bovine bone
      material augmentation or autologous bone grafting (chin and iliac crest).
      Survival rates were recorded for the overall number of implants (patients of
      group A). Apical and marginal bone levels (ABL and MBL, respectively) were
      radiographically measured, and statistical analysis was performed in implants of
      a subgroup of patients (group B). RESULTS: A total of 282 dental implants were
      positioned. Recorded cumulative survival rates (CSRs) were 95.6% and 100% for
      autogenous and bovine bone material, respectively, while CSRs at 2-year follow-up
      for immediate and delayed procedures were 99.3% and 96.5%. For the subgroup B, 57
      sinus augmentation procedures were performed in 39 patients, with the positioning
      of 154 implants. Generally, the apical- and marginal-bone resorption of the
      bovine bone-material group was less than that of the autogenous group. The
      differences between the ABL values of the bovine bone-material and iliac-crest
      groups were statistically significant at 1 year, whereas this significance
      disappeared at the 2-year follow-up; tests showed that a statistical difference
      was recorded in the bovine bone-material group between the 1- and 2-year follow
      ups. With regard to MBL comparisons between simultaneous and delayed
      implantation, the differences maintained their significance at the 2-year follow
      up also. CONCLUSIONS: Differences regarding apical bone alteration between
      autogenous bone from the iliac crest and bovine bone material at the 1- and 2
      year follow-ups, as well as in the bovine bone-material group between the 1- and
      2-year follow-ups, attested to slower but more prolonged physiologic bone
      remodeling in the bovine-graft-material group than in the autogenous-bone group.
      The MBL analysis showed that remodeling in the delayed implant group demonstrated
      a greater resorption in the cervical portion than was seen in the simultaneous
      implant group.

PMID- 21087316
TI  - Cortical porosity of the mandible in an osteoporotic sheep model.
AB  - OBJECTIVES: Cortical porosity and thickness of the axial and the appendicular
      skeleton are predictors of osteoporotic fractures. In the jawbone, however,
      cortical porosity and thickness may affect the mechanical stability of dental
      implants. We have shown previously that the jawbone of osteoporotic sheep has
      impaired trabecular structures, but whether catabolic bone turnover also accounts
      for the cortical bone porosity remains unknown. MATERIAL AND METHODS: We compared
      mandibular bone from six geriatric sheep subjected to ovariectomy,
      calcium/vitamin D restriction, and methylprednisolone administration to those of
      six healthy adult control sheep. Histological ground sections were prepared from
      the diastema, first and second premolars, and postmolar region. Cortical porosity
      and thickness were assessed by histomorphometry. RESULTS: Cortical porosity was
      higher in osteoporotic sheep than in adult controls in the diastema and in the
      first and second premolar region. In the postmolar region, the difference failed
      to reach the level of significance. The changes were even more prominent when
      histomorphometry was restricted to the inner millimeter of the mandibular cortex.
      In contrast, induction of osteoporosis did not have a discernable effect on
      cortical thickness. CONCLUSION: These results demonstrate that cortical porosity
      of mandibles is more pronounced in geriatric osteoporotic sheep than in adult
      controls.

PMID- 21087317
TI  - Sinus floor augmentation using large (1-2 mm) or small (0.25-1 mm) bovine bone
      mineral particles: a prospective, intra-individual controlled clinical, micro
      computerized tomography and histomorphometric study.
AB  - OBJECTIVES: To compare the amount of newly formed bone after sinus floor
      augmentation with two different particle sizes of bovine bone mineral (BBM) using
      clinical, micro-computerized tomography (CT) and histological techniques.
      METHODS: Bilateral sinus floor augmentations were performed in 10 patients. Six
      to 9 months later, bone samples were retrieved and analyzed. RESULTS: Results:
      Both groups were not different in vertical bone height achieved after
      augmentation, post-operative complications and maximal torque for the insertion
      of implants. Micro-CT measurements could not detect a statistically significant
      difference in bone volume between the groups (with a tendency for new more bone
      in the small granules group). Histomorphometric analysis revealed that both
      granule sizes produced the same pattern of bone formation, surrounding the graft
      granules, and producing a shape of a network, "bridging" between the BBM
      particles. Multi-nucleated giant cells, probably osteoclasts, were observed
      directly on the BBM particle surface in both groups. The osteoclast-like cells
      preferred the small-size BBM particles and not the large particles both in the
      small-size and the large-size granules group. CONCLUSION: Both sizes of BBM
      granules preformed equally and achieved the aim of the sinus floor augmentation
      procedure clinically and histologically.

PMID- 21087319
TI  - Progress and trends in patients' mindset on dental implants. I: level of
      information, sources of information and need for patient information.
AB  - OBJECTIVES: Little is known about the level of information on implant dentistry
      in the public. A representative opinion poll on dental implants in the Austrian
      population was published in 2003 (Clinical Oral Implants Research 14:621-642).
      Seven years later, the poll was rerun to assess the up-to-date information level
      and evaluate recent progress and trends in patients' mindset on dental implants.
      MATERIAL AND METHODS: One thousand adults--representative for the Austrian
      population--were presented with a total of 19 questionnaire items regarding the
      level and the sources of information about dental implants as well as the
      subjective and objective need for patient information. RESULTS: Compared with the
      survey of 2003, the subjective level of patient information about implant
      dentistry has significantly increased in the Austrian population. The patients'
      implant awareness rate was 79%. The objective level of general knowledge about
      dental implants was still all but satisfactory revealing unrealistic patient
      expectations. Three-quarters trusted their dentists for information about dental
      implants, while one-quarter turned to the media. The patients' wish for high
      quality implant restorations was significantly higher than in 2003, yet the
      majority felt that only specialists should perform implant dentistry.
      CONCLUSIONS: This representative survey reveals that dentists are still the main
      source of patient information, but throws doubt on the quality of their public
      relations work. Dentists must improve communication strategies to provide their
      patients with comprehensible, legally tenable information on dental implants and
      bridge information gaps in the future.

PMID- 21087318
TI  - Titanium nitride oxide coating on rough titanium stimulates the proliferation of
      human primary osteoblasts.
AB  - OBJECTIVES: Titanium is widely used in contemporary endosseous implantology and
      there is considerable thrust to further promote osseointegration by implant
      surface modifications. The aim of this study was to evaluate the effect of a
      titanium-nitride-oxide (TiNOx) coating on commercially pure microroughened
      titanium by assessing the proliferation and differentiation of human primary
      osteoblasts. MATERIALS AND METHODS: Cell proliferation, gene expression, alkaline
      phosphatase activity, osteoprotegerin and osteocalcin secretion were analyzed for
      a time course of 3 weeks, with or without additional stimulation by 1.25(OH)(2)
      vitamin D(3) 100 nM. RESULTS: A 1.5-fold increase in the proliferation rate of
      cells grown on TiNOx-coated titanium as compared with uncoated surfaces was
      observed. SEM views indicated that the cells' normal morphology with their
      numerous extensions was maintained. The differentiation process on the TiNOx
      surface was only affected to a minor degree and translated into a slight delay in
      osteoblast maturation when compared to uncoated titanium. CONCLUSION: Pending
      confirmation of these results in vivo, TiNOx coatings could potentially
      accelerate and enhance osseointegration.

PMID- 21087320
TI  - Primary stability, insertion torque and bone density of cylindric implant ad
      modum Branemark: is there a relationship? An in vitro study.
AB  - OBJECTIVES: Protocols of immediate loading have been reported in several studies.
      It has also been demonstrated that the cause of failure of immediate loaded
      implants is due to the micromotion on the bone-implant interface induced by
      immediate loading. There should be a minimum gap between the implant and the peri
      implant bone, without micromotions occurring above a definite threshold risk as
      they induce bone resorption and fibrosis around the implant. Measurement of the
      torque necessary to insert an implant in the bone is a parameter for measuring
      initial stability. The higher the implant insertion torque, the higher the
      initial stability attained. The aim of this study was to evaluate in vitro the
      correlation between the micromotion of cylindric screw implants ad modum
      Branemark and the insertion torque in bone of different densities. MATERIAL AND
      METHODS: The test was carried out on 2 * 2 cm samples of fresh bovine bone of
      three different densities: hard (H), medium (M) and soft (S). One hundred and
      fifty hexa implants ad modum Branemark were used, 3.75 mm in diameter and 9 mm
      long. To screw in the implants, a customized manual key was used, controlled
      digitally to evaluate the peak insertion torques. Ten implants were prepared for
      each torque (20, 35, 45, 70 and 100 N/cm). The bone sample was then fixed on a
      loading device, which allowed evaluating the micromotion. On each sample, we
      applied a 25 N horizontal force. RESULTS: The results indicate that the peak
      insertion torque and the implant micromotion are statistically correlated, and
      statistically significant differences in H and M bone were found compared with S
      bone. In S bone, we noted a micromotion significantly higher than the risk
      threshold, and it was not possible to reach peak insertion torque above 35 N/cm.
      In H and M bone, the micromotion is below the threshold of all insertion torques.
      CONCLUSIONS: Increasing the peak insertion torque, we can reduce the extent of
      the micromotion between the implant and the bone when submitted to lateral forces
      in vitro. In soft bone, the micromotion was always high; hence, immediate loading
      of implants in low-density bone should be evaluated with care.

PMID- 21087321
TI  - In vivo investigation on connective tissue healing to polished surfaces with
      different surface wettability.
AB  - OBJECTIVES: Connective tissue in contact to transgingival/-dermal implants
      presents itself as tight scar formation. Although rough surfaces support the
      attachment they increase bacterial colonisation as well. In contrast to surface
      roughness, little is known about the influence of surface wettability on soft
      tissue healing in vivo. We therefore investigated the influence of different
      surface wettabilities on connective tissue healing at polished implant surfaces
      in vivo. MATERIAL AND METHODS: Three polished experimental groups (titanium,
      titanium coated with hydrophobic nano-crystalline diamond (H-NCD) and titanium
      coated with hydrophilic nano-crystalline diamond (O-NCD) were inserted into the
      subcutaneous connective tissue of the abdominal wall of 24 rats. Animals were
      sacrificed after 1 and 4 weeks resulting in eight specimen per group per time
      point. Specimen were subjected to histological evaluation (van Giesson's
      staining) and immunohistochemistry staining for proliferating cell nuclear
      antigen (PCNA), fibronectin and tumour necrosis factor-alpha (TNF-alpha).
      RESULTS: Histological evaluation revealed dense scar formation at the titanium
      and H-NCD surfaces. In contrast, the connective tissue was loose at the O-NCD
      surface with a significantly higher number of cells after 4 weeks. O-NCD
      demonstrated a strong expression of PCNA and fibronectin but a weak expression of
      TNF-alpha. In contrast, the PCNA and fibronectin expression was low at the
      titanium and H-NCD, with a strong signal of TNF-alpha at the H-NCD surface.
      CONCLUSIONS: Hydrophilicity influences the connective tissue healing at polished
      implant surfaces in vivo positively. The attachment of connective tissue and the
      number of cells in contact to the surface were increased. Moreover, the
      inflammatory response is decreased at the hydrophilic surface.

PMID- 21087322
TI  - Response of experimental malignant melanoma models to the pan-Aurora kinase
      inhibitor VE-465.
AB  - Aurora kinases represent promising novel cancer therapy targets. Genomic analyses
      of human cutaneous melanoma (CMM) models (N = 51, low passage) by classical
      and/or array CGH revealed frequent gains at chromosome 20q (65%, amplifications
      in 45%) repeatedly including the Aurora A gene locus. Accordingly, the majority
      of CMM cell cultures overexpressed Aurora A when compared to proliferating non
      malignant cells. Moreover, CMM cells even when arrested in G1/S cell cycle phase
      contained readily detectable levels of Aurora A indicating incomplete degradation
      during mitosis. Already at low concentrations (10-100 nm), long-term (7-10 days)
      application of the pan-Aurora kinase inhibitor VE-465 completely prevented colony
      formation in all CMM models tested. In contrast, blockade of cell
      survival/proliferation and DNA synthesis as well as the induction of apoptosis by
      VE-465 distinctly differed in short-term experiments (up to 72 h exposure). Both
      cell cycle arrest and DNA synthesis blockade depended on the level of VE-465
      mediated p53/p21 activation while p53/p21 unresponsiveness led to repetitive
      endoreduplication (>8n DNA content). In contrast, apoptosis induction by VE-465
      and Aurora A siRNA did not correlate with p53/p21 responsiveness and DNA
      synthesis blockade. Moreover, application of the Aurora B-specific inhibitor
      ZM447439 and siRNA was less efficient to induce CMM cell death proofing that
      apoptosis induction by VE-465 depended predominantly on Aurora A targeting. In
      combination experiments with chemotherapeutic agents, VE-465 acted additive to
      antagonistic when applied concomitantly but in several cases even synergistic
      when applied consecutively. In summary, we suggest that the Aurora A kinase might
      represent a promising target of well-designed novel antimelanoma strategies.

PMID- 21087323
TI  - Hint for association of single nucleotide polymorphisms and haplotype in SPINK5
      gene with atopic dermatitis in Koreans.
AB  - Clinical studies, including twin studies, support the concept that the risk of
      atopic dermatitis (AD) may be mediated through skin-specific genes, rather than
      simply through systemic immune or atopy risk genes. The SPINK5 gene is expressed
      on epithelial surfaces and may provide protection against other allergenic serine
      proteases. Mutations in the SPINK5 gene result in Netherton syndrome, a disorder
      characterised by AD, ichthyosis, and elevated serum IgE levels. We genotyped 21
      single nucleotide polymorphisms (SNPs) from the SPINK5 gene for 1090 case-control
      samples (631 patients with AD and 459 normal controls) and analysed the SNPs and
      haplotypes in this gene and also searched for gene-gene interactions between
      SPINK5 and the DEFB1 gene that we previously reported. Six SNPs [rs17718511 (P =
      0.026), rs17860502 (P = 0.024), KN0001820 (P = 0.045), rs60978485 (P = 0.007),
      rs17718737 (P = 0.02), and rs1422985 (P = 0.038)] and the haplotype TAA
      (rs60978485, rs6892205, rs2303064; P = 0.023) in the SPINK5 gene showed
      significant different allelic or genotypic distributions between the AD group and
      the control group. We also found that four SNPs [rs17718511 (P = 0.033),
      rs17860502 (P = 0.031), rs60978485 (P = 0.005), rs17718737 (P = 0.023)] and the
      haplotype TAA (P = 0.02) in the SPINK5 gene showed associations with the
      susceptibility of the allergic type of AD (ADe). In addition to this finding, we
      speculate that the SNPs from DEFB1 and SPINK5 affect the individual
      susceptibility to development of ADe in an additive manner. This study provides
      evidence for a significant interaction between allergens and the SPINK5 gene that
      may contribute to ADe susceptibility.

PMID- 21087324
TI  - Strong exercise stress exacerbates dermatitis in atopic model mice, NC/Nga mice,
      while proper exercise reduces it.
AB  - Atopic dermatitis is well known to exacerbate by stress. How the influence of
      exercise stress on the skin symptoms in patients with atopic dermatitis has not
      been clarified. The purpose of our research is to investigate how different
      strength of exercise stress acts on atopic dermatitis. Specific pathogen-free
      (SPF) and conventional NC/Nga male mice were used for the experiments.
      Conventional mice but not SPF group spontaneously develop dermal symptom similar
      to that of patients with atopic dermatitis at their age of 7 weeks. They were
      given two types of stress, mild (20 m/min for 60 min) or strong exercise (25
      m/min for 90 min), using a treadmill four times per day. The dermal symptom of
      the conventional group was strongly exacerbated by strong exercise but
      ameliorated by mild exercise. Under the standard experimental conditions, plasma
      concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH), transforming
      growth factor-beta (TGF-beta) and substance P in conventional mice increased
      markedly with concomitant exacerbation of the symptom. The plasma concentrations
      of these proteins elevated after strong exercise but decreased after mild
      exercise. Under the conventional conditions, plasma levels of beta-endorphin
      increased with time by some mechanisms enhanced by the mild exercise. These
      observations suggested that exercise-induced stress significantly affect the
      symptom of atopic dermatitis in a pivotal manner depending on the plasma levels
      of TGF-beta, alpha-MSH, substance P and beta-endorphin.

PMID- 21087325
TI  - Phylogeography of the Afromontane Prunus africana reveals a former migration
      corridor between East and West African highlands.
AB  - Scattered populations of the same tree species in montane forests through Africa
      have led to speculations on the origins of distributions. Here, we inferred the
      colonization history of the Afromontane tree Prunus africana using seven
      chloroplast DNA loci to study 582 individuals from 32 populations sampled in a
      range-wide survey from across Africa, revealing 22 haplotypes. The predominant
      haplotype, HT1a, occurred in 13 populations of eastern and southern Africa, while
      a second common haplotype, HT1m, occurred in populations of western Uganda and
      western Africa. The high differentiation observed between populations in East
      Africa was unexpected, with stands in western Uganda belonging with the western
      African lineage. High genetic differentiation among populations revealed using
      ordered alleles (N(ST) = 0.840) compared with unordered alleles (G(ST) = 0.735),
      indicated a clear phylogeographic pattern. Bayesian coalescence modelling
      suggested that 'east' and 'west' African types likely split early during
      southward migration of the species, while further more recent splitting events
      occurred among populations in the East of the continent. The high genetic
      similarity found between western Uganda and west African populations indicates
      that a former Afromontane migration corridor may have existed through Equatorial
      Africa.

PMID- 21087326
TI  - Nitrogen deposition mediates the effects and importance of chance in changing
      biodiversity.
AB  - Nitrogen deposition is changing biodiversity on Earth. We need to understand the
      underlying mechanisms to conserve biodiversity better. Both selection and chance
      are potential mechanisms, and they may operate concurrently. Then, what are the
      respective effects of selection and chance, what is their relative importance and
      how do they change with increasing nitrogen deposition rate? Here, we performed a
      6-year nitrogen addition experiment (0-28 g N/m(2) /year) in a typical steppe
      ecosystem of Inner Mongolia to investigate the community structure of plants,
      bacteria and ammonia-oxidizing Archaea (AOA). We developed an experimentally
      based calculation method to first separate the structural variations between
      plots into the effects of selection (S) and chance (C), and then calculate their
      relative importance. Our results showed that as nitrogen addition rate increased,
      S for both plants and bacteria increased, but C for plants first increased and
      then decreased, and C for bacteria also increased; meanwhile, both S and C for
      AOA changed nonlinearly. As nitrogen addition rate increased, the importance of
      chance decreased on the whole for all these communities, but it decreased
      nonlinearly for plants and bacteria, with a local increase at certain
      intermediate rates. At all treatments, the importance of chance was <0.5 for
      plants, but >0.5 for AOA. These results demonstrated that nitrogen deposition
      changed biodiversity by mediating the effects and importance of chance,
      implicating different strategies should be adopted in conserving biodiversity
      according to nitrogen deposition rate and community properties.

PMID- 21087327
TI  - Ablation of right-sided accessory pathways with atrial insertion far from the
      tricuspid annulus using an electroanatomical mapping system.
AB  - BACKGROUND: It is difficult to ablate a right-sided accessory pathway (AP) with
      atrial insertion far from the tricuspid annulus (TA). We report our initial
      experience of ablating this rare AP by a 3-dimensional electroanatomical mapping
      system (CARTO). METHODS: From January of 2006 to April of 2008, 18 patients with
      right-sided APs who failed previous outside ablations were enrolled in this
      study. Retrograde AP conduction was mapped during pacing at the right ventricular
      apex by activation-mapping the right atrium (RA) using a 3-dimensional
      electroanatomical mapping system. AP atrial insertion was defined as the earliest
      retrograde atrial activations and successful ablation of the APs at this site.
      RESULTS: Among the 18 patients who had failed previous ablation, 10 patients (7
      patients with right manifest APs and 3 patients with right conceal APs) had
      atrial insertions far from the TA. Of the 10 patients, the atrial insertions were
      found at the base of the RA appendage in 3 patients, at the high lateral RA in 5
      patients, at the low lateral RA in other 2 patients. Ablation at the atrial
      insertions successfully abolished the AP conduction. The mean distance between
      the atrial insertion sites and the TA was 20.2 +/- 2.7 mm. No patients reported
      recovered AP conduction or recurrent tachycardias after 6-month follow-up.
      CONCLUSIONS: The right-sided APs may have atrial insertion far from the TA. These
      uncommon variation of APs can be reliably identified and ablated using CARTO
      system.

PMID- 21087328
TI  - Physiologic resynchronization therapy: a case of his bundle pacing reversing
      physiologic conduction in a patient with CHF and LBBB during 2 years of
      observation.
AB  - This is a case of a patient with congestive heart failure and left bundle branch
      block who was referred for cardiac resynchronization therapy implantation.
      Instead, a His bundle pacing was achieved with a narrow QRS complex. During 27
      months of observation, the patient improved dramatically from NYHA class IV to I.
      Echo parameters improved significantly the LV diameter from 75/50 to 60/40 mm, EF
      from 28 to 50%, and mitral regurgitation from 4 to 2 degrees .

PMID- 21087330
TI  - Endothelial dysfunction and atrial fibrillation: what is the relationship?

PMID- 21087329
TI  - Trends in US hospitalization rates and rhythm control therapies following
      publication of the AFFIRM and RACE trials.
AB  - INTRODUCTION: The impact of trials comparing rate versus rhythm control for AF on
      subsequent use of rhythm control therapies and hospitalizations at a national
      level has not been described. METHODS AND RESULTS: We queried the Healthcare Cost
      & Utilization Project on the frequency of hospital admissions and performance of
      specific rhythm control procedures from 1998-2006. We analyzed trends in
      hospitalization for AF as principal diagnosis before and after the publication of
      key rate versus rhythm trials in 2002. We also reviewed the use of electrical
      cardioversion and catheter ablation as principal procedures during hospital
      admissions for any cause and for AF as principal diagnosis. We additionally
      appraised the overall outpatient utilization of antiarrhythmic drugs during this
      same time frame using IMS Health's National Prescription Audit.TM Admissions for
      AF as a principal diagnosis increased at 5%/year from 1998-2002. Following
      publication of the AFFIRM and RACE trials in 2002, admissions declined by 2%/year
      from 2002-2004, before rising again from 2004-2006. In-hospital electrical
      cardioversion followed a similar pattern. National prescription volumes for
      antiarrhythmic drugs grew at <1% per year from 2002 to 2006, with a marked
      decline in the use of class I-A agents, while catheter ablations during
      admissions for AF as the principal diagnosis increased at 30% per year.
      CONCLUSION: The use of rhythm control therapies in the US declined significantly
      in the first few years after publication of AFFIRM and RACE. This trend reversed
      by 2005, at which time rapid growth in the use of catheter ablation for AF was
      observed.

PMID- 21087331
TI  - Appropriate and inappropriate electrical therapies delivered by an implantable
      cardioverter-defibrillator: effect on intracardiac electrogram.
AB  - INTRODUCTION: Local injury current (LIC) seen after induced ventricular
      fibrillation rescue implantable cardioverter-defibrillator (ICD) shock predicts
      heart failure progression. We sought to determine the frequency of LIC after
      spontaneous events in patients receiving ICD therapies. METHODS AND RESULTS: Near
      field (NF) right ventricular (RV) EGM during 10 seconds after delivered ICD
      therapy was compared with baseline EGM in 420 events that occurred in 134
      patients (mean age 60.8 +/- 14.8, 106 [79%] male). The magnitude of elevated or
      depressed potential immediately after the major fast EGM deflection was defined
      as LIC, and its ratio to the peak-to-peak EGM amplitude was defined as relative
      LIC. LIC of at least 1 mV or relative LIC of at least 15% was considered
      significant. LIC was observed in 121 events (28.8%) and was detected more
      frequently after appropriate (43 [60.6%] events) and inappropriate (56 [64.4%]
      events) ICD shocks, as compared with appropriate (8 [9.2%] events) and
      inappropriate (3 [4.7%] events) antitachycardia pacing (ATP) or nonsustained
      ventricular tachycardia (11 [9.9%] events) [ANOVA P < 0.0001]. Type of ICD
      therapy (ICD shock vs ATP) was the most significant predictor of LIC (ATP beta
      coefficient -0.81; 95%CI-1.19 to 0.44); P < 0.0001), along with cycle length of
      tachycardia (beta coefficient -0.0117; 95%CI -0.0167 to -0.0068, P < 0.00001) and
      shock energy (beta coefficient 0.024; 95%CI 0.003-0.045, P = 0.025). CONCLUSION:
      Appropriate and inappropriate ICD shocks are frequently characterized by the
      development of LIC in patients with structural heart disease. Type of electrical
      ICD therapy, shock energy and cycle length of ventricular arrhythmia are
      important determinants of LIC.

PMID- 21087332
TI  - Selective CFAE targeting for atrial fibrillation study (SELECT AF): clinical
      rationale, design, and implementation.
AB  - BACKGROUND: Adjuvant ablation of complex fractionated atrial electrograms (CFAE)
      in addition to pulmonary vein isolation (PVI) likely improves procedural outcome
      compared to PVI alone, particularly in patients with persistent atrial
      fibrillation (AF). However, CFAE regions can be extensive, occasionally requiring
      a large amount of extra ablation. Some CFAE regions may also represent passive
      wavefront collision and may not require ablation. Thus, there is interest in
      identifying more selective CFAE sites that are critical to AF perpetuation,
      minimizing the amount of adjuvant ablation that must be performed. OBJECTIVE: The
      SELECT AF study is a prospective, multicenter, randomized trial comparing a
      strategy of PVI plus generalized CFAE ablation versus a strategy of PVI plus
      selective CFAE ablation, focusing on regions of continuous electrical activity
      (CEA). The primary efficacy endpoint is freedom from atrial arrhythmia at 1 year
      and the primary safety endpoint is total radiofrequency (RF) delivery time per
      procedure. METHODS: Patients undergoing a first time ablation procedure for
      symptomatic persistent AF will be included. Patients with permanent AF or with
      left atrial size >=55 mm will be excluded. Patients will all receive PVI at the
      time of their ablation, but will be randomized 1:1 to receive adjuvant CFAE
      ablation using the traditional "generalized" approach, or a "selective" approach
      targeting only CEA regions. Both strategies will be guided by automated mapping
      algorithms. This study will enroll a minimum of 80 evaluable subjects; 40 in each
      randomization group. CONCLUSIONS: SELECT AF is a randomized trial in patients
      with persistent AF to evaluate the efficacy of selective versus generalized CFAE
      ablation in addition to traditional PVI.

PMID- 21087333
TI  - Methods for evaluation of humoral immune responses in human genital tract
      secretions.
AB  - The compilation of epidemiological, virological, and immunological data clearly
      indicates that HIV-1 infection must be considered primarily as a disease of the
      mucosal immune system. The earliest and most dramatic alterations of the immune
      system occur in the mucosal compartment. However, the mucosal immune systems of
      the genital and intestinal tracts display remarkable immunological differences
      that must be considered in the evaluation of humoral immune responses in HIV-1
      infected individuals or in volunteers immunized with experimental HIV vaccines.
      In this regard, marked differences in the dominant Ig isotypes, molecular forms
      of HIV-1-specific antibodies, and their distinct effector functions in the
      genital versus intestinal tracts must be carefully evaluated and considered in
      the measurement and interpretation of humoral immune responses. Appropriate
      controls and alternative immunochemical assays should be used to complement and
      confirm results generated by ELISA, which are prone to false positivity. Special
      precautions and rigorous controls must be used in the evaluation of antibody
      mediated virus neutralization in external secretions of the genital and
      intestinal tracts.

PMID- 21087334
TI  - High Frequency of anti-protein Z IgM and IgG autoantibodies in women with
      idiopathic recurrent spontaneous miscarriage.
AB  - PROBLEM:  Protein Z (PZ) system is an anticoagulant pathway involved in the
      physiologic regulation of coagulation, and PZ deficiency reportedly enhances
      prothrombophilic mechanisms, including those implicated with idiopathic recurrent
      miscarriage (RSM). We investigate plasma anti-PZ IgM and IgG levels in RSM women
      and in multiparous control women. METHODS: Anti-PZ IgM and IgG levels were
      measured in 265 RSM women and 283 age-matched control women by ELISA. RESULTS:
      Elevated anti-PZ IgG (P < 0.001) and IgM (p < 0.001) titers were seen in
      patients. The areas under the curves for ROC curve for anti-PZ IgM (0.898 +/-
      0.044) and IgG (0.898 +/- 0.042) demonstrated no variation in diagnostic
      capacity. Multivariate analysis confirmed the association of elevated anti-PZ IgM
      [adjusted odds ratio, aOR (95% CI) = 6.46 (2.44-17.11)] and IgG [aOR (95% CI) =
      7.44 (2.54-21.79)] as independent predictors of RSM after adjusting for
      confounding covariates and demonstrated a clear gradation of increasing RSM risk
      associated with increased antibody titers. CONCLUSION: The presence of anti-PZ
      IgM and IgG antibodies are risk factors for RSM.

PMID- 21087335
TI  - Fas-FasL system in molar pregnancy.
AB  - PROBLEM: Hydatidiform mole (molar pregnancy) is the commonest form of Gestational
      Trophoblastic Disease, with the risk of undergoing malignant transformation. The
      molecular pathway leading to pathogenesis and progression of molar pregnancy is
      barely understood. The study focuses on Fas/FasL system which represents one of
      the main apoptotic pathways controlling placental morphogenesis. METHOD OF STUDY:
      Placental tissues from 52 patients with complete hydatidiform moles (CHMs) and
      55 age-matched controls were examined for Fas and FasL expression using
      immunohistochemistry, immunofluorescence and Western blotting. The protein
      expression was also correlated with trophoblast apoptosis (assessed by M30 Cyto
      DEATH), clinico-pathological parameters and disease progression. RESULTS:  
      Immunohistochemistry and immunofluorescence revealed both cytoplasmic and
      membranous expression of Fas in villous syncytiotrophoblast as well as
      cytotrophoblast but FasL was confined merely to the cytoplasm of
      syncytiotrophoblast. Both Fas (cytoplasm and membrane) and FasL were
      significantly upregulated in syncytiotrophoblast of CHMs (P = 0.004, P < 0.0001
      and P < 0.0002 respectively) and showed a positive association between them (P =
      0.019). However, none of the proteins reveal any correlation with M30 index. The
      results were revalidated using Western blotting. CONCLUSION: This study
      demonstrated differential expression of Fas and FasL in CHMs and its implications
      in the pathogenesis of molar pregnancy has been discussed.

PMID- 21087336
TI  - Focal increases of fetal macrophages in placentas from pregnancies with
      histological chorioamnionitis: potential role of fibroblast monocyte chemotactic
      protein-1.
AB  - PROBLEM:  Histopathological chorioamnionitis (HCA) is caused by microbial-driven
      infiltration of leukocytes to the maternal-fetal interface resulting in adverse
      neonatal outcomes in a subset of pregnancies. The role of placental villus
      macrophages (i.e. Hofbauer cells, HBCs) in the pathophysiology of HCA is
      unelucidated. METHOD OF STUDY:  The number of HBCs in human term placental villi
      in HCA and control groups was compared using immunohistochemistry. Levels of
      monocyte chemotactic protein (MCP-1) expression were measured in primary cultures
      of syncytioytrophoblasts (SCTs) and fibroblasts (FIBs) treated with bacterial
      compounds [lipopolysaccharide (LPS) and peptidoglycan] and pro-inflammatory
      cytokines (TNF-alpha and IL-1beta) using ELISA and quantitative real-time PCR.
      RESULTS:  Immunohistochemistry revealed a focal increase in HBCs in HCA.
      Treatment of FIBs with LPS, IL-1beta, and TNF-alpha significantly increased MCP-1
      mRNA and protein expression. Conversely, MCP-1 mRNA and protein levels were
      virtually undetectable in treated and untreated SCTs. CONCLUSION:  These results
      demonstrate cell-type-specific regulation of MCP-1 expression in human placenta.
      A model is presented in which bacterial products and inflammatory cytokines
      initiate a fibroblast-driven cytokine cascade resulting in recruitment of fetal
      monocytes to placenta which focally increases levels of HBCs in pregnancies
      complicated by HCA.

PMID- 21087337
TI  - Pathophysiological roles of chemokines in human reproduction: an overview.
AB  - Chemokines are a group of small cytokines that have an ability to induce
      leukocyte migration. Chemokines exert their functions by binding and activating
      specific G protein-coupled receptors. Studies have unveiled pleiotropic
      bioactivities of chemokines in various phenomena ranging from immunomodulation,
      embryogenesis, and homeostasis to pathogenesis. In the mammalian reproductive
      system, chemokines unexceptionally serve in multimodal events that are closely
      associated with establishment, maintenance, and deterioration of fecundity. The
      aim of this review is to update the knowledge on chemokines in male and female
      genital organs, with a focus on their potential pathophysiological roles in human
      reproduction.

PMID- 21087339
TI  - Role of semen in HIV-1 transmission: inhibitor or facilitator?
AB  - Sexual transmission of human immunodeficiency virus type 1 (HIV-1) accounts for
      60-90% of new infections, especially in developing countries. During male-to
      female transmission, the virus is typically deposited in the vagina as cell-free
      and cell-associated virions carried by semen. But semen is more than just a
      carrier for HIV-1. Evidence from in vitro and in vivo studies supports both
      inhibitory and enhancing effects. Intrinsic antiviral activity mediated by
      cationic antimicrobial peptides, cytotoxicity, and blockage of HIV-dendritic cell
      interactions are seminal plasma properties that inhibit HIV-1 infection. On the
      contrary, neutralization of vaginal acidic pH, enhanced virus-target cell
      attachment by seminal amyloid fibrils, opsonization by complement fragments, and
      electrostatic interactions are factors that facilitate HIV-1 infection. The end
      result, i.e., inhibition or enhancement of HIV mucosal infection, in vivo, likely
      depends on the summation of all these biological effects. More research is
      needed, especially in animal models, to dissect the role of these factors and
      establish their relevance in HIV-1 transmission.

PMID- 21087338
TI  - Hormonal contraception and HIV-1 transmission.
AB  - Safe and effective contraceptive choices are essential for women with HIV-1
      infection and at risk for HIV-1 infection. Epidemiological and laboratory-based
      studies suggest that hormonal contraception may influence HIV-1 transmission.
      Several large studies in high-risk populations indicate that hormonal
      contraceptive use may modestly increase the risk of HIV-1 acquisition. In
      addition, HIV-1-infected users of hormonal contraceptives may be more infectious
      to their uninfected partners, although no studies have directly measured HIV-1
      transmission risk from women to men. However, several studies failed to
      demonstrate a link between contraceptive use and HIV-1 acquisition or
      transmission, and interpretation of many studies limited by methodological
      considerations, such as infrequent measurements of contraceptive exposure and HIV
      1 status. As a result, many questions remain, and high-quality studies remain
      needed. It is clear that hormonal contraceptives are not protective against HIV-1
      infection and that dual protection with condoms should be the goal for women
      using hormonal contraception.

PMID- 21087340
TI  - Cortical bone stress distribution in mandibles with different configurations
      restored with prefabricated bar-prosthesis protocol: a three-dimensional finite
      element analysis.
AB  - PURPOSE: To evaluate stress distribution in different horizontal mandibular arch
      formats restored by protocol-type prostheses using three-dimensional finite
      element analysis (3D-FEA). MATERIALS AND METHODS: A representative model (M) of a
      completely edentulous mandible restored with a prefabricated bar using four
      interforaminal implants was created using SolidWorks 2010 software (Inovart, Sao
      Paulo, Brazil) and analyzed by Ansys Workbench 10.0 (Swanson Analysis Inc.,
      Houston, PA) to obtain the stress fields. Three mandibular arch sizes were
      considered for analysis, regular (M), small (MS), and large (ML). Three
      unilateral posterior loads (L) (150 N) were used: perpendicular to the
      prefabricated bar (L1); 30 degrees  oblique in a buccolingual direction (L2); 30
      degrees  oblique in a lingual-buccal direction (L3). The maximum and minimum
      principal stresses (sigma(max), sigma(min)), the equivalent von Mises
      (sigma(vM)), and the maximum principal strain (sigma(max) ) were obtained for
      type I (M.I) and type II (M.II) cortical bones. RESULTS: Tensile stress was more
      evident than compression stress in type I and II bone; however, type II bone
      showed lower stress values. The L2 condition showed highest values for all
      parameters (sigma(vM), sigma(max), sigma(min), E(max)). The sigma(vM) was highest
      for the large and small mandibular arches. CONCLUSION: The large arch model had a
      higher influence on sigma(max) values than did the other formats, mainly for type
      I bone. Vertical and buccolingual loads showed considerable influence on both
      sigma(max) and sigma(min) stresses.

PMID- 21087341
TI  - A prospective analysis of immediate provisionalization of single implants.
AB  - PURPOSE: The purpose of this prospective study was to evaluate the viability of
      immediately provisionalized single-tooth implants. MATERIALS AND METHODS: One
      hundred forty patients (86 female, 54 male) with a mean age at implant placement
      of 45 years (range, 15-88 years) needing single-tooth replacement, were treated
      between July 1999 and December 2004. Single-tooth implants were placed and
      provisionalized the day of the surgery. All implants were manufactured by Nobel
      Biocare (Yorba Linda, CA) and had multiple diameters and configurations. The
      majority of the implants used in this study had oxidized titanium surfaces. The
      contours of the restorations were designed to mimic the original teeth and root
      forms. The morphology of the restorations provides support of the labial gingiva.
      RESULTS: Over 5.5 years, 164 implants were placed and immediately
      provisionalized. Sixty-four implants were placed immediately post extraction.
      Seven implants failed, yielding an overall survival rate of 95.73%. CONCLUSION:
      The application of an immediate provisionalization protocol to a single implant
      can be successful if the proper precautions are taken in achieving passive
      occlusion.

PMID- 21087342
TI  - The expression of CXCR4 and its relationship with matrix metalloproteinase
      9/vascular endothelial growth factor in esophageal squamous cell cancer.
AB  - Esophageal cancer (EC) is a highly aggressive neoplasm with poor prognosis. The
      main reason for this disappointing outcome is the strong behavior of esophageal
      cancer cell's invasion and metastasis. CXC chemokine receptor 4 (CXCR4) was found
      to be expressed in many tumors and significantly correlated with invasion,
      angiogenesis, metastasis, and prognosis. In the present study, we investigated
      the expressions of CXCR4, matrix metalloproteinase-9 (MMP-9), and vascular
      endothelial growth factor (VEGF) in esophageal squamous cell cancer (ESCC) and
      analyzed the relationship among the three proteins. Sections of paraffin-embedded
      tissues were obtained from 127 patients with ESCC undergoing esophagectomy at
      Zhongshan Hospital, Fudan University in 2005. The CXCR4, MMP-9, and VEGF
      expressions in EC tissues were evaluated according to the immunohistochemical
      staining area and intensity. The correlations between patients' prognosis and
      covariates were analyzed by Kaplan--Meier method (univariate analysis) and Cox
      regression (multivariate analysis). The overall expression rate of CXCR4, MMP-9,
      and VEGF was 88.2%, 93.7%, and 79.5%, respectively. CXCR4 expression was
      significantly associated with tumor grade, tumor size, tumor depth, regional
      lymph node metastasis, and tumor, node, metastasis (TNM) stage (P < 0.05). MMP-9
      expression was significantly associated with age and tumor grade (P < 0.05). VEGF
      expression was significantly associated with tumor grade, tumor depth, and TNM
      stage (P < 0.05). CXCR4 expression was positively correlated with MMP-9
      expression (P < 0.01, r= 0.365) and VEGF expression (P < 0.01, r= 0.380).
      However, there was no significant correlation between MMP-9 and VEGF expression
      (P > 0.05). In univariate analysis, CXCR4 expression, tumor size, tumor depth,
      lymph node metastasis, and TNM stage were correlated with patients' prognosis (P
      < 0.05); in multivariate analysis, tumor size and lymph node metastasis were the
      independent factors of poor prognosis. CXCR4 was highly expressed in ESCC and
      correlated with MMP-9, VEGF, clinicopathological features and prognosis. We
      speculated CXCR4 play an important role during the progression of this disease
      and there might be some regulatory mechanism existing between CXCR4 and MMP
      9/VEGF in ESCC.

PMID- 21087343
TI  - Effects of ursodeoxycholic acid in esophageal motility and the role of the
      mucosa. An experimental study.
AB  - Esophageal motor abnormalities are frequently found in patients with
      gastroesophageal reflux disease. The role of bile in reflux-induced dysmotility
      is still elusive. Furthermore, it is questionable weather mucosal or muscular
      stimulation leads to motor dysfunction. The aims of this study were to analyze
      (i) the effect of bile in the amplitude of esophageal contractions; and (ii) the
      effect of mucosal versus muscular stimulation. Eighteen guinea pig esophagi were
      isolated, and its contractility assessed with force transducers. Three groups
      were studied. In group A (n= 6), the entire esophagus was incubated in 100 umL
      ursodeoxycholic acid for 1 hour; in group B (n= 6) the mucosal layer was removed
      and the muscular layer incubated in 100 umL ursodeoxycholic acid for 1 hour; and
      in group C (n= 6) (control group) the entire esophagus was incubated in saline
      solution. In all groups, five sequential contractions induced by 40 mm KCl spaced
      by 5 minutes were measured before and after incubation. Contractions amplitudes
      before incubation were 1.319 g, 0.306 g, and 1.795 g, for groups A, B, and C,
      respectively. There were no differences between groups A and C (P= 0.633), but
      there were differences between groups A and B (P= 0.039), and B and C (P= 0.048).
      After incubation amplitude of contraction were 0.709 g, 0.278 g, and 1.353 g for
      groups A, B, and C, respectively. Only group A showed difference when pre and
      post-stimulation amplitudes were compared (P= 0.030). Our results show that (i)
      bile exposure decreases esophageal contraction amplitude; and (ii) the esophageal
      mucosa seems to play an important role in esophageal motility.

PMID- 21087344
TI  - The radiosensitization effect of NS398 on esophageal cancer stem cell-like
      radioresistant cells.
AB  - This study aimed to investigate the cancer stem cell (CSC) properties of
      radioresistant esophageal cancer cells and the radiosensitization effect of
      NS398, a cyclooxygenase (COX)-2 inhibitor, on them. Fractionated irradiation was
      applied to acquire radioresistant esophageal cancer cells. Clone formation assay
      was employed to detect cell radiosensitivity and cloning formation ability. Cell
      viability was determined by methyl tetrazolium colorimetry assay. Cell cycle
      distribution and apoptosis were detected by flow cytometry. Tumorigenicity was
      investigated by xenograft tumorigenicity assay. Expression levels of beta-catenin
      were detected by reverse transcription polymerase chain reaction or Western blot.
      As results, radioresistant Eca109R50Gy cells were obtained through fractional
      irradiation from Eca109 cells; Eca109R50Gy cells displayed higher ability of
      proliferation, colony-formation, and 40 times tumorigenic ability as high as that
      of the Eca109 cells in vivo. Meantime stem cell marker beta-catenin was elevated
      in Eca109R50Gy cells. All of the above implied that Eca109R50Gy cells have some
      properties of CSCs. NS398 enhanced the radiosensitivity of Eca109R50Gy cells
      accompanied by down-regulating the expression of beta-catenin. In conclusion,
      radioresistant Eca109R50Gy cells carried some CSC-like properties; NS398 enhanced
      the radiosensitivity of CSC-like Eca109R50Gy cells and this function may partly
      through down-regulating the expression of beta-catenin. These findings both
      stress the important role of CSCs in esophageal cancer radioresistance and
      provide new insight on possible application of COX-2 inhibitors on CSCs.

PMID- 21087345
TI  - Simultaneous operation of concomitant diseases in the esophagus and lung.
AB  - The aim of this study was to retrospectively review our experience of performing
      simultaneous operations on concomitant diseases in the esophagus and lungs. From
      January 1998 to July 2009, simultaneous operations were performed on 13 patients
      with concomitant esophageal and pulmonary diseases, using coordinated surgical
      approaches. Among the 13 patients, six had primary cancers in the esophagus and
      lungs, five had primary esophageal cancer accompanied by a benign pulmonary
      disease, one had benign diseases in both esophagus and lung, and one had primary
      esophageal cancer with metastasis to the left lower lung. All patients survived
      the operations. Two major complications occurred postoperatively. One
      complication was bronchopleural fistula and the other was intrathoracic gastric
      laceration. Both patients recovered after additional treatments. Simultaneous
      operation of concomitant diseases in the esophagus and lungs is feasible and safe
      in selected patients who have received careful preoperative assessment, well
      designed surgical approach, and proper perioperative management.

PMID- 21087346
TI  - Persistent dysphagia after removal of an adjustable gastric band for morbid
      obesity: a rare complication.
AB  - Esophageal and gastric pouch dilatations are not uncommon after laparoscopic
      adjustable gastric banding for morbid obesity. Most of the cases are treated by
      gastric band deflation or removal. We report here the case of a 44-year-old woman
      with vomiting and severe dysphagia persisting despite gastric band removal, in
      relation with a scar stenosis and a gastric pouch trapped in the thorax, treated
      by laparoscopic surgery. This case underlines the usefulness of high-resolution
      manometry in the diagnostic work-up of these often difficult cases.

PMID- 21087347
TI  - Submucosal tumor appearance is a useful endoscopic predictor of early primary
      site recurrence after definitive chemoradiotherapy for esophageal squamous cell
      carcinoma.
AB  - Chemoradiotherapy (CRT) for esophageal cancer is disadvantageous because of a
      high locoregional failure rate. Detecting early small recurrent cancers at the
      primary site is necessary for potential salvage treatment. However, most
      endoscopists are inexperienced and therefore, a role for surveillance endoscopy
      after complete remission (CR) has not been established. We retrospectively
      evaluated serial surveillance endoscopic images from patients eventually proved
      to have primary-site recurrence in order to identify useful endoscopic features
      for early diagnosis. From January 2000 to December 2004, 303 patients with
      esophageal squamous cell carcinoma underwent definitive CRT, and 133 of them
      achieved CR. The surveillance endoscopic images stored at intervals of 1-3 months
      for the 16 patients with recurrence only at the primary tumor site and the 61
      patients with no recurrence were collected for reexamination. Among 133 patients
      who achieved CR, 16 (12%) developed only local recurrence at the primary site.
      Thirteen of the 16 primary-site recurrent tumors (81%) appeared as submucosal
      tumors (SMT), with the remaining appearing as erosions or mild strictures. Of
      biopsy-proven recurrences, 81% were preceded by newly developed lesions such as
      SMT, erosions, or mild strictures detected by earlier surveillance endoscopies.
      For all 77 patients achieving CR with no metastasis, 86% of the evolving SMT with
      negative biopsies were eventually confirmed as cancer at later endoscopies.
      Thirteen of the 21 evolving lesions were subsequently confirmed as recurrent
      cancer. Early primary-site recurrence of esophageal cancer after a complete
      response to CRT is detectable with frequent endoscopic surveillance. SMT
      appearance is a useful endoscopic sign of early recurrence, as well as a
      predictor of subsequent diagnosis of recurrence.

PMID- 21087348
TI  - Aspergillus fumigatus colonization in cystic fibrosis: implications for lung
      function?
AB  - Aspergillus fumigatus is commonly found in the respiratory secretions of patients
      with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis
      (ABPA) is associated with deterioration of lung function, the effects of A.
      fumigatus colonization on lung function in the absence of ABPA are not clear.
      This study was performed in 259 adults and children with CF, without ABPA. A.
      fumigatus colonization was defined as positivity of >50% of respiratory cultures
      in a given year. A cross-sectional analysis was performed to study clinical
      characteristics associated with A. fumigatus colonization. A retrospective cohort
      analysis was performed to study the effect of A. fumigatus colonization on lung
      function observed between 2002 and 2007. Longitudinal data were analysed with a
      linear mixed model. Sixty-one of 259 patients were at least intermittently
      colonized with A. fumigatus. An association was found between A. fumigatus
      colonization and increased age and use of inhaled antibiotics. In the
      longitudinal analysis, 163 patients were grouped according to duration of
      colonization. After adjustment for confounders, there was no significant
      difference in lung function between patients colonized for 0 or 1 year and
      patients with 2-3 or more than 3 years of colonization (p 0.40 and p 0.64)
      throughout the study. There was no significant difference in lung function
      decline between groups. Although colonization with A. fumigatus is more commonly
      found in patients with more severe lung disease and increased treatment burden,
      it is not independently associated with lower lung function or more severe lung
      function decline over a 5-year period.

PMID- 21087349
TI  - New HCV therapies on the horizon.
AB  - Improved understanding of the hepatitis C virus (HCV) life cycle has led to the
      discovery of numerous potential targets for antiviral therapy. HCV polyprotein
      processing and replication have been identified as the most promising viral
      targets. However, viral entry and fusion, RNA translation, virus assembly and
      release and several host cell factors may provide alternative attractive targets
      for future anti-HCV therapies. Inhibitors of the HCV NS3/4A protease are
      currently the most advanced in clinical development. Monotherapy with protease
      inhibitors has shown high antiviral activity, but is associated with frequent
      selection of resistant HCV variants, often resulting in viral breakthrough.
      However, there is encouraging evidence from phase 2/3 trials indicating that the
      addition of a protease inhibitor (e.g. telaprevir and boceprevir) to pegylated
      interferon-alpha/ribavirin substantially improves sustained virological response
      rates in both treatment-naive and treatment-experienced patients with HCV
      genotype 1. Nucleos(t)ide inhibitors of the HCV NS5B polymerase have shown
      variable antiviral activity against different HCV genotypes, but seem to have a
      higher genetic barrier to resistance than protease inhibitors. In addition,
      several allosteric binding sites have been identified for non-nucleoside
      inhibitors of the NS5B polymerase. However, the development of a substance with
      high antiviral activity and a high genetic barrier to resistance seems to be
      difficult. Among the different host cell-targeting compounds in early clinical
      development, cyclophilin inhibitors have shown the most promising results.
      Although advances have also been made in improving interferons, combinations of
      antiviral agents with different mechanisms of action may lead to the eventual
      possibility of interferon-free regimens.

PMID- 21087350
TI  - Long interspersed nuclear element-1 hypomethylation is a potential biomarker for
      the prediction of response to oral fluoropyrimidines in microsatellite stable and
      CpG island methylator phenotype-negative colorectal cancer.
AB  - We investigated the clinical value of methylation of long interspersed nuclear
      element-1 (LINE-1) for the prognosis of colorectal cancer (CRC) and for the
      survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. LINE-1
      methylation in tumor DNA was measured by quantitative methylation-specific PCR in
      155 samples of stage II and stage III CRC. The presence of microsatellite
      instability and CpG island methylator phenotype (CIMP) were assessed and 131
      microsatellite stable/CIMP- cases were selected for survival analysis, of which
      77 patients had received postoperative adjuvant chemotherapy with oral
      fluoropyrimidines. The CRC cell lines were used to investigate possible
      mechanistic links between LINE-1 methylation and effects of 5-fluorouracil (5
      FU). High LINE-1 methylation was a marker for better prognosis in patients
      treated by surgery alone. Patients with low LINE-1 methylation who were treated
      with adjuvant chemotherapy survived longer than those treated by surgery alone,
      suggestive of a survival benefit from the use of oral fluoropyrimidines. In
      contrast, a survival benefit from chemotherapy was not observed for patients with
      high LINE-1 methylation. The CRC cell lines treated with 5-FU showed increased
      expression of LINE-1 mRNA. This was associated with upregulation of the phospho
      histone H2A.X in cells with low LINE-1 methylation, but not in cells with high
      LINE-1 methylation. The 5-FU-mediated induction of phospho-histone H2A.X, a
      marker of DNA damage, was inhibited by knockdown of LINE-1. These results suggest
      that LINE-1 methylation is a novel predictive marker for survival benefit from
      adjuvant chemotherapy with oral fluoropyrimidines in CRC patients. This finding
      could be important for achieving personalized chemotherapy.

PMID- 21087351
TI  - Hispidulin, a small flavonoid molecule, suppresses the angiogenesis and growth of
      human pancreatic cancer by targeting vascular endothelial growth factor receptor
      2-mediated PI3K/Akt/mTOR signaling pathway.
AB  - Hispidulin, an active component from Artemisia vestita, a traditional Tibetan
      medicinal plant, has been shown to possess anti-inflammatory and anti-oxidative
      activities. However, the functional role of hispidulin on tumor growth and
      angiogenesis has not been elucidated. We found that hispidulin significantly
      inhibited human pancreatic tumor growth in xenograft mice when s.c. treated at a
      dosage of 20 mg/kg daily, and this effect was accompanied with a potent
      inhibition on angiogenesis. When examining the cytotoxicity of hispidulin on
      HUVECs and pancreatic cancer cells in vitro, we found that HUVECs were more
      susceptible to the treatment, suggesting angiogenesis might be the primary target
      of hispidulin. Our results further showed that hispidulin inhibited vascular
      endothelial growth factor (VEGF)-induced cell migration, invasion, and capillary
      like structure formation of HUVECs in a dose-dependent manner. In ex vivo and in
      vivo angiogenesis assays, we showed that hispidulin suppressed VEGF-induced
      microvessel sprouting of rat aortic rings and corneal neovascularization in
      C57/BL6 mice. To understand the underlying molecular basis, we next examined the
      effects of hispidulin on different molecular components in treated HUVECs, and
      found that hispidulin suppressed the VEGF-triggered activation of VEGF receptor
      2, PI3K, Akt, mTOR, and ribosomal protein S6 kinase, but had little effect on
      focal adhesion kinase or extracellular signal-regulated kinase at an effective
      concentration. Taken together, our results indicate that hispidulin targets the
      VEGF receptor 2-mediated PI3K/Akt/mTOR signaling pathway in endothelial cells,
      leading to the suppression of pancreatic tumor growth and angiogenesis.

PMID- 21087352
TI  - Peptides derived from human insulin-like growth factor-II mRNA binding protein 3
      can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive
      to cancer cells.
AB  - Insulin-like growth factor-II mRNA binding protein 3 (IMP-3) is an oncofetal
      protein expressed in various malignancies including lung cancer. This study aimed
      to identify immunogenic peptides derived from IMP-3 that can induce tumor
      reactive and human leukocyte antigen (HLA)-A2 (A*02:01)-restricted cytotoxic T
      lymphocytes (CTL) for lung cancer immunotherapy. Forty human IMP-3-derived
      peptides predicted to bind to HLA-A2 were analyzed to determine their capacity to
      induce HLA-A2-restricted T cells in HLA-A2.1 (HHD) transgenic mice (Tgm). We
      found that three IMP-3 peptides primed HLA-A2-restricted CTL in the HLA-A2.1 Tgm.
      Among them, human CTL lines reactive to IMP-3 (515) NLSSAEVVV(523) were
      reproducibly established from HLA-A2-positive healthy donors and lung cancer
      patients. On the other hand, IMP-3 (199) RLLVPTQFV(207) reproducibly induced IMP
      3-specific and HLA-A2-restricted CTL from healthy donors, but did not sensitize
      CTL in the HLA-A2.1 Tgm. Importantly, these two IMP-3 peptide-specific CTL
      generated from healthy donors and cancer patients effectively killed the cancer
      cells naturally expressing both IMP-3 and HLA-A2. Cytotoxicity was significantly
      inhibited by anti-HLA class I and anti-HLA-A2 monoclonal antibodies, but not by
      the anti-HLA-class II monoclonal antibody. In addition, natural processing of
      these two epitopes derived from the IMP-3 protein was confirmed by specific
      killing of HLA-A2-positive IMP-3-transfectants but not the parental IMP-negative
      cell line by peptide-induced CTL. This suggests that these two IMP-3-derived
      peptides represent highly immunogenic CTL epitopes that may be attractive targets
      for lung cancer immunotherapy.

PMID- 21087353
TI  - Enhanced expression of nuclear factor I/B in oxaliplatin-resistant human cancer
      cell lines.
AB  - Oxaliplatin is a third-generation platinum drug that has favorable activity in
      cisplatin-resistant cells. However, the molecular mechanisms underlying
      oxaliplatin resistance are not well understood. To investigate the molecular
      mechanisms involved, resistant cell lines were independently derived from colon
      cancer (DLD1) and bladder cancer (T24) cells. Oxaliplatin-resistant DLD1 OX1 and
      DLD1 OX2 cell lines were approximately 16.3-fold and 17.8-fold more resistant to
      oxaliplatin than the parent cell lines, respectively, and had 1.7- and 2.2-fold
      higher cross-resistance to cisplatin, respectively. Oxaliplatin-resistant T24 OX2
      and T24 OX3 cell lines were approximately 5.0-fold more resistant to oxaliplatin
      than the parent cell line and had 1.9-fold higher cross-resistance to cisplatin.
      One hundred and fifty-eight genes commonly upregulated in both DLD1 OX1 and DLD1
      OX2 were identified by microarray analysis. These genes were mainly involved in
      the function of transcriptional regulators (14.6%), metabolic molecules (14.6%),
      and transporters (9.5%). Of these, nuclear factor I/B (NFIB) was upregulated in
      all oxaliplatin-resistant cells. Downregulation of NFIB rendered cells sensitive
      to oxaliplatin, but not to cisplatin. Forced expression of NFIB induced
      resistance to oxaliplatin, but not to cisplatin. Taken together, these results
      suggest that NFIB is a novel and specific biomarker for oxaliplatin resistance in
      human cancers.

PMID- 21087354
TI  - Glial cell line-derived neurotrophic factor is a key neurotrophin in the
      postnatal enteric nervous system.
AB  - BACKGROUND: The enteric nervous system (ENS) continues its structural and
      functional growth after birth, with formation of ganglia and the innervation of
      growing smooth muscle. However, little is known about factors in the postnatal
      intestine that influence these processes. METHODS: We examined the presence and
      potential role of glial cell line-derived nerve growth factor (GDNF) in the rat
      postnatal ENS using neonatal tissue, primary co-cultures of the myenteric plexus,
      smooth muscle, and glial cells as well as cell lines of smooth muscle or glial
      cells. KEY RESULTS: Western blot analysis showed that GDNF and its co-receptors
      rearranged during transfection (RET) and GDNF family receptor alpha-1 were
      expressed in the muscle layer of the neonatal and adult rat intestine.
      Immunohistochemistry localized the receptors for GDNF to myenteric neurons, while
      GDNF was localized to smooth muscle cells. In a co-culture model, GDNF but not
      nerve growth factor, brain derived neurotrophic factor or neurotrophin-3
      significantly increased neuronal survival and more than doubled the numbers of
      neurites in vitro. RT-PCR, qPCR, Western blotting, ELISA, and immunocytochemistry
      as well as bioassays of neuronal survival and of RET phosphorylation all
      identified intestinal smooth muscle as the source of GDNF in vitro. GDNF also
      induced morphological changes in the structure and organization of neurons and
      axons, causing marked aggregation of neuronal cell bodies and collinear
      development of axons. As well, GDNF (50-150 ng mL(-1)) significantly increased
      [(3)H]-choline uptake and stimulated [(3)H]-acetylcholine release. CONCLUSIONS &
      INFERENCES: We conclude that GDNF derived from intestinal smooth muscle cells is
      a key factor influencing the structural and functional development of postnatal
      myenteric neurons.

PMID- 21087355
TI  - Concomitant irritable bowel syndrome is associated with failure of step-down on
      demand proton pump inhibitor treatment in patients with gastro-esophageal reflux
      disease.
AB  - BACKGROUND: The predictors for treatment failure of on-demand proton pump
      inhibitor (PPI) therapy in gastro-esophageal reflux disease (GERD) patients are
      unclear. We studied the efficacy and predictors for treatment failure of step
      down on-demand PPI therapy in patients with non-erosive reflux disease (NERD) and
      those with low grade erosive esophagitis. METHODS: Consecutive symptomatic GERD
      patients who had positive esophageal pH studies and complete symptom resolution
      with initial treatment of esomeprazole were given step-down on-demand
      esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C
      or above and recent use of PPI were excluded. Treatment failure was defined as an
      inadequate relief of reflux symptoms using global symptom assessment. Potential
      predictors of treatment failure were determined using multivariate analysis. KEY
      RESULTS: One hundred and sixty three NERD and 102 esophagitis patients were
      studied. The 26-week probability of treatment failure was 36.2% (95% CI: 23.9
      46.5%) in NERD group and 20.1% (95% CI: 10.9-28.3%) in esophagitis group,
      respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5
      3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7,
      95% CI: 1.9-4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio:
      1.7, 95% CI: 1.1-2.8, P = 0.04), were independent predictors for treatment
      failure. CONCLUSIONS & INFERENCES: Compared to patients with esophagitis, NERD
      patients have higher failure rate of on-demand PPI therapy. Concomitant irritable
      bowel syndrome, in addition to daily reflux symptom and dyspepsia, is associated
      with the failure of on-demand PPI in these patients.

PMID- 21087356
TI  - Measurement of gastric emptying of a high-nutrient liquid by 3D ultrasonography
      in diabetic gastroparesis.
AB  - BACKGROUND: Gastric emptying (GE) is delayed in 30-50% of patients with
      longstanding diabetes. Scintigraphy represents the 'gold standard' for
      measurement of GE, but is associated with a radiation burden. Three-dimensional
      (3D) ultrasonography has recently been demonstrated to provide a valid measure of
      liquid GE in healthy subjects; however, the technique has not been validated in
      patients with gastroparesis. The primary aim of this study was to compare
      measurements of GE of a high-nutrient glucose drink by 3D ultrasonography and
      scintigraphy in diabetic gastroparesis. METHODS: Ten patients (eight type 1, two
      type 2, 6M, 4F, aged 46.1 +/- 4.5 years, BMI 29.1 +/- 1.6 kg m(-2), duration 19.6
      +/- 3.3 years) with diabetic gastroparesis [defined as retention at 100 min of
      solid (100 g minced beef) >= 61% and/or 50% emptying time (T50) of liquid (150 mL
      10% dextrose) >= 31 min], were studied. Concurrent measurements of GE by
      scintigraphy and 3D ultrasonography were performed following ingestion of 75 g
      glucose in 300 mL water labeled with 20 MBq (99m) Tc-sulfur colloid. KEY RESULTS:
      There was no significant difference in GE between the two techniques (T50s:
      scintigraphy - 103.3 +/- 10.0 min VS 3D ultrasonography - 98.8 +/- 10.4 min; P =
      0.60). There was a significant correlation between scintigraphic and
      ultrasonographic T50s (r = 0.67, P = 0.03). The limits of agreement for the T50s
      were -57.22 min and +48.22 min (mean difference -4.5 min). Blood glucose after
      the drink was greater when GE was relatively more rapid (e.g. at t = 60 min;
      scintigraphy: r = -0.65, P = 0.04; 3D ultrasonography: r = -0.78, P = 0.008).
      CONCLUSIONS & INFERENCES: Three-dimensional ultrasonography appears to provide a
      valid, and non-invasive, measure of GE of high-nutrient liquids in diabetic
      gastroparesis.

PMID- 21087357
TI  - Extracellular signal-regulated kinase (ERK) is involved in LPS-induced
      disturbances in intestinal motility.
AB  - BACKGROUND: Lipopolysaccharide (LPS) is a causative agent of sepsis. A
      relationship has been described between LPS, free radicals, and cyclooxygenase-2
      (COX-2). Here, we investigate the role of extracellular signal-regulated kinase
      (ERK) mitogen-activated protein kinases (MAPK) in the effect of LPS on intestinal
      motility, oxidative stress status, and COX-2 expression. METHODS: Rabbits were
      injected with (i) saline, (ii) LPS, (iii) U0126, an ERK MAPK inhibitor, or (iv)
      U0126+LPS. Duodenal contractility was studied in an organ bath with
      acetylcholine, prostaglandin E(2), and KCl added. Neuromuscular function was
      assessed by electrical field stimulation (EFS). Neurotransmitter blockers were
      used to study the EFS-elicited contractile response. The formation of products of
      oxidative damage to proteins (carbonyls), lipids, [malondialdehyde (MDA), and 4
      hydroxyalkenals (4-HDA)] was quantified in plasma and intestine. The protein
      expression of phospho-ERK (p-ERK), total ERK, and COX-2 in the intestine was
      measured by western blot, and p-ERK was localized by immunohistochemistry. KEY
      RESULTS: Acetylcholine, prostaglandin E(2), and KCl-induced contractions
      decreased with LPS. Electrical field stimulation induced a neurogenic contraction
      that was reduced by LPS. Lipopolysaccharide increased p-ERK and COX-2 expression
      and the levels of carbonyls and MDA+4-HDA. U0126 blocked the effect of LPS on
      acetylcholine, prostaglandin E(2), KCl, and EFS-induced contractions, the levels
      of carbonyls and MDA+4-HDA and p-ERK and COX-2 expression. Phospho-ERK was
      detected mostly in the neurons of the myenteric and submucosal ganglia.
      CONCLUSIONS & INFERENCES: We can suggest that ERK is involved in the mechanism of
      action of LPS in the intestine.

PMID- 21087359
TI  - Valacyclovir neurotoxicity can be effectively managed by hemodialysis.

PMID- 21087360
TI  - Evaluation of health-related quality of life, fatigue and depression in
      neuromyelitis optica.
AB  - BACKGROUND: The burden of multiple sclerosis (MS) includes fatigue, depression
      and worsening of health-related quality of life (HRQOL). These changes have not
      been yet measured in neuromyelitis optica (NMO). Our aim was to assess the HRQOL,
      fatigue and depression in NMO. METHODS: We administered French validated self
      questionnaires on HRQOL (SEP-59), fatigue (EMIF-SEP) and depression (EHD) to 40
      patients followed up in two centres. We assessed the relationship of these
      parameters with gender, age, disability, disease duration, visual acuity and NMO
      antibody status and also compared our results with equivalent data in MS and
      normal subjects derived from previous studies. RESULTS: Health-related quality of
      life scores were lower (P < 0.01) in patients with NMO when compared to normal
      subjects. No significant difference was noted between patients with NMO and MS
      for most scores, the exceptions being HRQOL related to cognitive function (better
      in NMO than in MS), HRQOL related to sphincter dysfunction (worse in NMO than in
      MS) and the psychological dimension of fatigue (milder in NMO than in MS).
      Disability was the main predictive factor of an unfavourable evolution.
      DISCUSSION: This study reveals the strong impact of NMO on HRQOL, fatigue and
      depression and the importance of screening patients, especially the more
      disabled, so as to initiate suitable treatment.

PMID- 21087361
TI  - Childhood refractory focal epilepsy following acute febrile encephalopathy.
AB  - BACKGROUND: We describe a group of previously normal children who developed
      severe focal epilepsy after an acute/sub-acute illness resembling encephalitis.
      METHODS: This is a retrospective study. An acute phase
      (encephalitis/encephalopathy period) and a chronic phase (chronic focal resistant
      epilepsy) were defined. RESULTS: Eight patients were enrolled. The median age at
      onset was 6.6 years (range 8 months-17.6 years). In the acute phase, fever was
      the first symptom in all cases and was associated with seizures and status
      epilepticus. All patients had focal seizures arising in both hemispheres. Seizure
      onset occurred in the frontal and temporal regions. EEGs showed slowing
      background activity associated with focal or diffuse slow waves with rare
      epileptiform abnormalities. Cerebrospinal fluid oligoclonal bands were observed
      in four out of six patients tested. MRI images showed bilateral peri-insular
      hyperintensity in four cases. Five patients received corticosteroids, and in four
      cases, they were given along with intravenous immunoglobulins. The median
      duration of the acute phase was 19 days (range 15-30 days). During the chronic
      phase, which followed the acute phase without interval, patients presented with
      drug-resistant focal seizures and neuropsychological deficits, which ranged from
      hyperactivity and attention deficits to short-term verbal memory deficit,
      pervasive developmental disorders, and language delay. CONCLUSION: Considering
      the clinical presentations, EEG findings, and the associated occurrence of non
      specific immunological activations, a possible immune-mediated pathogenesis can
      be hypothesized, although firm conclusions cannot be drawn out.

PMID- 21087362
TI  - Low frequency stimulation of the nucleus tegmenti pedunculopontini increases
      cortical metabolism in parkinsonian patients.
AB  - BACKGROUND AND PURPOSE: To evaluate the effects of 25-Hz deep brain stimulation
      of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity.
      METHODS: Six patients with Parkinson's disease (PD) who had bilateral
      stereotactic implantation of PPTg at least 12 months prior to evaluation were
      included in our study. All underwent, in separate sessions, 18-FDG-PET in core
      assessment programme for intra-cerebral transplantation as well as motor
      evaluation [Unified Parkinson's disease rating scale (UPDRS)--Section III] and a
      battery of cognitive testing. RESULTS: PPTg-ON (low bipolar contacts, 25 Hz)
      promoted a significant increase of glucose utilization in bilateral prefrontal
      areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito-frontal
      cortex (BA47), anterior cingulate (BA 25-32), superior frontal gyrus (BA 10) and
      supramarginal gyrus (BA40); a significant increase of uptake and consumption of
      FDG also occurred in the left ventral striatum, left subgyral (BA 46), right
      insula (BA 13) and right superior temporal gyrus (BA 22). PPTg-ON was associated
      with a significant decrease of glucose utilization in the left cerebellar
      anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same
      patients, PPTg-ON improved delayed recall (P < 0.05) and executive functions
      whilst the UPDRS revealed a modest (-21%) and variable treatment effect.
      CONCLUSIONS: Low frequency stimulation of PPTg, a sub-region of the
      pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar
      profile of cognitive improvement associated with a significant increase in FDG
      consumption in both prefrontal areas and mono-lateral ventral striatum. These
      data are consistent with multiple limbic and/or associative domains modulated by
      PPTg stimulation in our patients with PD.

PMID- 21087363
TI  - Perimetric and peri-papillary nerve fibre layer thickness findings in multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Several previous studies have employed optical coherence
      tomography (OCT) of the optic disc and 'white-on-white' automated perimetry to
      evaluate optic neuritis (ON) associated with multiple sclerosis (MS). This study
      employed OCT, white-on-white automated perimetry as well as 'blue-on-yellow'
      automated perimetry to evaluate MS patients with or without episodes of ON.
      METHODS: The MS group consisted of 56 patients with MS (27 patients with no
      history of ON in both eyes and 29 patients with at least one ON attack in one or
      both eyes), whereas the control group consisted of 56 age- and sex-matched
      healthy subjects. All patients underwent a complete neurological and
      ophthalmological examination. Peri-papillary retinal nerve fibre layer thickness
      (RNFLT) was evaluated using OCT. The mean defect and pattern standard deviation
      for both white-on-white and blue-on-yellow perimetry were also recorded. RESULTS:
      RNFLT and perimetric scores were significantly lower in MS group without a
      history of ON and in the unaffected eyes of MS group with unilateral ON, compared
      with controls. MS group with more than one ON episodes had significantly
      compromised blue-on-yellow perimetric indices, compared with patients with one ON
      episode, whereas respective differences for white-on-white perimetry were not
      statistically significant. CONCLUSIONS: The significantly lower RNFLT and
      perimetric scores in MS group patients without ON, compared with control group,
      may possibly be attributed to sub-clinical episodes of ON or to retrograde
      degeneration of nerve cells from sub-clinical post-chiasmal lesions. Blue-on
      yellow perimetry may be advantageous over white-on-white perimetry in evaluating
      MS-associated functional defects.

PMID- 21087364
TI  - VPS54 genetic analysis in ALS Italian cohort.

PMID- 21087365
TI  - Evaluation of nurse-led discharge following laparoscopic surgery.
AB  - INTRODUCTION: The United Kingdom's Department of Health has identified reducing
      delays in patient discharge as a key aim for Health Service development.
      Laparoscopic cholecystectomy and laparoscopic inguinal hernia repair may be
      safely performed on a short stay basis, but day case rates remain low, with
      delays in discharge identified as a major contributing factor. Nurse-led
      discharge has been widely advocated to speed patient discharge across varied
      specialities, but objective evidence to support its use is lacking. This study
      aimed to assess the effectiveness of nurse-led discharge following laparoscopic
      surgery. METHODS: A retrospective comparison of doctor-led and nurse-led
      discharge following laparoscopic surgery was performed by analysis of two
      consecutive 4-month periods, prior to and following the introduction of nurse-led
      discharge by a laparoscopic nurse specialist. Outcomes assessed included time to
      discharge, reasons for delayed discharge, hospital readmissions and primary care
      episodes following discharge. RESULTS: A total of 128 patients were included in
      the study, with each discharge group containing 64 patients. Patients in the
      nurse-led discharge group were significantly more likely to be discharged on the
      day of surgery than patients in the doctor-led discharge group (17.2% vs. 4.7%; P
      = 0.023), with a highly significant difference in same day discharge rates noted
      among patients operated on during morning theatre lists (44.0% vs. 10.7%; P =
      0.006). There was no significant difference between the discharge groups in
      readmission rates or in the number of patients seeking primary care attention
      following discharge. CONCLUSIONS: Nurse-led discharge may speed discharge
      following laparoscopic surgery with no apparent detriment to patient care.

PMID- 21087366
TI  - Clinical audit and quality improvement - time for a rethink?
AB  - RATIONALE AND AIM: Evidence of the benefits of clinical audit to patient care is
      limited, despite its longevity. Additionally, numerous attitudinal, professional
      and organizational barriers impede its effectiveness. Yet, audit remains a
      favoured quality improvement (QI) policy lever. Growing interest in QI techniques
      suggest it is timely to re-examine audit. Clinical audit advisors assist health
      care teams, so hold unique cross-cutting perspectives on the strategic and
      practical application of audit in NHS organizations. We aimed to explore their
      views and experiences of their role in supporting health care teams in the audit
      process. METHOD: Qualitative study using semi-structured and focus group
      interviews. Participants were purposively sampled (n = 21) across health sectors
      in two large Scottish NHS Boards. Interviews were audio-taped, transcribed and a
      thematic analysis performed. RESULTS: Work pressure and lack of protected time
      were cited as audit barriers, but these hide other reasons for non-engagement.
      Different professions experience varying opportunities to participate. Doctors
      have more opportunities and may dominate or frustrate the process. Audit is
      perceived as a time-consuming, additional chore and a managerially driven
      exercise with no associated professional rewards. Management failure to support
      and resource changes fuels low motivation and disillusionment. Audit is regarded
      as a 'political' tool stifled by inter-professional differences and contextual
      constraints. CONCLUSIONS: The findings echo previous studies. We found limited
      evidence that audit as presently defined and used is meeting policy makers'
      aspirations. The quality and safety improvement focus is shifting towards
      'alternative' systems-based QI methods, but research to suggest that these will
      be any more impactful is also lacking. Additionally, identified professional,
      educational and organizational barriers still need to be overcome. A debate on
      how best to overcome the limitations of audit and its place alongside other
      approaches to QI is necessary.

PMID- 21087367
TI  - The evidence-based medicine model of clinical practice: scientific teaching or
      belief-based preaching?
AB  - RATIONALE: Evidence-based medicine (EBM) is commonly advocated as a 'gold
      standard' of clinical practice. A prominent definition of EBM is: the integration
      of best research evidence with clinical expertise and patient values. Over time,
      various versions of a conceptual model or framework for implementing EBM (i.e.
      how to practice EBM) have been developed. AIMS AND OBJECTIVES: This paper (i)
      traces the evolution of the different versions of the conceptual model; (ii)
      tries to make explicit the underlying goals, assumptions and logic of the various
      versions by exploring the definitions and meaning of the components identified in
      each model, and the methods suggested for integrating these into clinical
      practice; and (iii) offers an analytic critique of the various model iterations.
      METHODS: A literature review was undertaken to identify, summarize, and compare
      the content of articles and books discussing EBM as a conceptual model to guide
      physicians in clinical practice. RESULTS: Our findings suggest that the EBM model
      of clinical practice, as it has evolved over time, is largely belief-based,
      because it is lacking in empirical evidence and theoretical support. The model is
      not well developed and articulated in terms of defining model components,
      justifying their inclusion and suggesting ways to integrate these in clinical
      practice. CONCLUSION: These findings are significant because without a model that
      clearly defines what constitutes an EBM approach to clinical practice we cannot
      (i) consistently teach clinicians how to do it and (ii) evaluate whether it is
      being done.

PMID- 21087368
TI  - The application of pharmacoeconomic modelling to estimate a value-based price for
      new cancer drugs.
AB  - RATIONALE, AIMS AND OBJECTIVES: Value-based pricing has recently been discussed
      by international bodies as a means to estimate a drug price that is linked to the
      benefits it offers patients and society. The World Health Organization (WHO) has
      recommended using three times a country's per capita gross domestic product (GDP)
      as the threshold for economic value. Using the WHO criteria, pharmacoeconomic
      modelling was used to illustrate the application of value-based price towards
      bevacizumab, a relatively new drug that provides a 1.4-month survival benefit to
      patients with metastatic colorectal cancer (mCRC). METHODS: A decision model was
      developed to simulate outcomes in mCRC patients receiving chemotherapy +/-
      bevacizumab. Clinical data were obtained from randomized trials and costs from
      Canadian cancer centres. Utility estimates were determined by interviewing 24
      oncology nurses and pharmacists. A price per dose of bevacizumab was then
      estimated using a target threshold of $CAD117,000 per quality adjusted life year
      gained, which is three times the Canadian per capita GDP. RESULTS: For a 1.4
      month survival benefit, a price of $CAD830 per dose would be considered cost
      effective from the Canadian public health care perspective. If the drug were able
      to improve patient quality of life or survival from 1.4 to 3 months, the drug
      price could increase to $CAD1560 and $CAD2180 and still be considered cost
      effective. DISCUSSION: The use of the WHO criteria for estimating a value-based
      price is feasible, but a balance between what patients/governments can afford to
      pay and the commercial viability of the product in the reference country would be
      required.

PMID- 21087369
TI  - Patientsmate(c): the implementation and evaluation of an online prospective audit
      system.
AB  - INTRODUCTION: Inaccuracy in Hospital Inpatient Enquiry (HIPE)/Casemix-based data
      has been reported as high as 26%. This results in financial waste and makes
      effective audit impossible. We aimed to develop a novel web-based outcome audit
      system. METHODS: A web-based online audit system, Patientsmate(c), was developed
      using an integrated database system written in the programme language PHP. Data
      were inputted by the surgical team responsible for the patients care. A
      prospective comparison study of the new Patientsmate(c) and the standard HIPE
      systems, was performed over a 1-month period and involving two general surgical
      teams in April 2010. In addition, a Likert-scale based questionnaire was designed
      and hosted within the Patientsmate(c) system. A focus group of those clinicians
      directly involved in data accessing and input were then invited to complete the
      questionnaire in order to assess usability of the system. RESULTS: During the
      study period there were a total of 108 patients and 88 procedures. Our study
      confirms the accuracy of clinician derived data, with the Patientsmate(c) system
      more accurately recording number of patients (83% vs. 80.6%), number of
      procedures (85.2% vs. 68.1%) and hospital day case rate (52% vs. 47.1%).
      Inputting data using Patientsmate(c) for a single patient took 6-7 minutes. Of
      those using the system, 75% reported feeling comfortable after using it once only
      and 100% were satisfied with the layout of the online interface. CONCLUSION: The
      Patientsmate(c) system allows for increased accuracy in outcome-based data as
      compared with the HIPE system, facilitating audit, financial savings and the
      appropriate allocation of services.

PMID- 21087370
TI  - Measuring how well the NHS looks after its own staff: methodology of the first
      national clinical audits of occupational health services in the NHS.
AB  - RATIONALE, AIMS AND OBJECTIVES: Little is known about the quality of occupational
      health care provided to National Health Service (NHS) staff. We designed the
      first national clinical audits of occupational health care in England. We chose
      to audit depression and back pain as health care workers have high levels of both
      conditions compared with other employment sectors. The aim of the audits was to
      drive up quality of care for staff with these conditions. The object of this
      paper is to describe how we developed an audit methodology and overcame
      challenges presented by the organization and delivery of occupational health care
      for NHS staff. METHODS: We designed two retrospective case note audits which ran
      simultaneously. Sites submitted up to 40 cases for each audit. We used duplicate
      case entry to test inter-rater reliability and performed selection bias checks.
      Participants received their site's audit results, benchmarked against the
      national average, within 4 months of the end of the data entry period. We used
      electronic voting at a results dissemination conference to inform implementation
      activities. RESULTS: Occupational Health departments providing services to 278
      (83%) trusts in England participated in one or both audits. Median kappa scores
      were above 0.7 for both pilot and full audits, indicating 'good' levels of inter
      rater reliability. In total, 79% of participants at a dissemination conference
      said that they had changed their clinical practice either during data collection
      (52%) or following receipt of their audit results (27%). CONCLUSIONS: Clinical
      audit can be conducted successfully in the occupational health setting. We
      obtained meaningful data that have stimulated local and national quality
      improvement activities. Our methodology would be transferable to occupational
      health settings outside the NHS and in other countries.

PMID- 21087371
TI  - Person-centred integrative care.
AB  - RATIONALE, AIMS AND OBJECTIVES: The essential ingredients of effective person
      centred integrative care are described and its benefits are documented in terms
      of influence on compliance with care, drop-out rates, enhancement of well-being
      and reduction in ill-being. METHOD: Prior literature on efficacy of person
      centred treatment in medicine and psychology is reviewed and related to
      definitions of health and well-being. RESULTS: The general characteristics of
      person-centred care involve multiple elements. First, the doctor must be aware of
      the personality of the individual in order to enter into a humanistic dialogue
      with the person. Second, for a therapeutic alliance, there must be agreement that
      doctor and patient are working toward common goals. Third, calm reassurance,
      hope, and respect need to be communicated. Fourth, the doctor and patient need to
      be empathic and reflective. Fifth, they must identify and implement practical
      means of promoting health with available resources and a realistic understanding
      of facts. CONCLUSION: Awareness of who the person is in a therapeutic encounter
      allows cultivation of a humanistic dialogue, which in turn accounts for most of
      the variation in clinical outcomes.

PMID- 21087372
TI  - The value of tailored communication for person-centred outcomes.
AB  - RATIONALE: When entering a consulting room a person becomes a patient with double
      needs, that is, the need to feel known and understood and the need to know and
      understand, also referred to as affective and instrumental needs, respectively.
      The fulfilment of these needs highly depends on the communication skills of both
      doctor and patient, which help to bridge the inherent distance that exists
      between these two persons. There is ample evidence that this bridge becomes
      stronger the more the communication is tailored to the person behind the patient.
      Besides, such tailored communication may also prove to be effective for reaching
      favourable health outcomes. METHODS: Descriptive study focusing on the value of
      tailored communication in promoting person-centred instrumental and affective
      health outcomes. RESULTS: Research shows that tailored communication contributes
      to health outcomes known to be crucial for recovery and quality of life, that is,
      information recall, medication adherence, reassurance and need fulfilment.
      CONCLUSION: There is empirical evidence for the value of tailored communication
      for person-centred outcomes. Communicating in a purposeful way while at the same
      time respecting patients' values and feelings should therefore become the
      standard in health care practice.

PMID- 21087373
TI  - Patients' beliefs about medicines in a primary care setting in Germany.
AB  - OBJECTIVES: The aim of this study was to explore patients' beliefs about
      medicines by administering the German version of the Beliefs about Medicines
      Questionnaire (BMQ) in a primary care setting among chronically ill patients and
      to examine its psychometric properties. The BMQ assesses patients' beliefs about
      their individual prescribed medication as well as their beliefs about medicines
      in general. METHODS: A cross-sectional survey of 485 chronically ill patients was
      performed. The German version of the BMQ was evaluated in terms of internal
      consistency, validity and scale structure. To assess validity the Medication
      Adherence Report Scale (MARS-D) and the Satisfaction with Information about
      Medicines Scale (SIMS-D) were applied. RESULTS: The BMQ showed good internal
      consistency (Cronbach's alpha 0.79-0.83). Patients' belief about the specific
      necessity of their medicines correlated positively with the MARS-D (rho = 0.202;
      P < 0.01). There were significant correlations in the predicted direction between
      the MARS-D and all the BMQ subscales with the exception of the General-Overuse
      subscale (rho = -0.06; P = 0.30). Relationship to the SIMS-D was comparable to
      the original study. Factor analysis corroborated the scale structure.
      CONCLUSIONS: The BMQ is a suitable instrument to measure patients' beliefs in
      medicines in German primary care settings. Most patients in our sample had
      positive beliefs concerning the necessity of their medication. Their levels of
      concern were associated with higher non-adherence.

PMID- 21087375
TI  - Duration of cough, TB suspects' characteristics and service factors determine the
      yield of smear microscopy.
AB  - OBJECTIVE: To determine the efficiency of routine tuberculosis (TB) case
      detection by examining sputum smear positivity for acid-fast bacilli in relation
      to duration of cough, characteristics of TB suspects examined and health service
      factors. METHOD: We combined patient interviews with routine data from laboratory
      registers in 6 health care facilities in San Juan de Lurigancho district, Lima,
      Peru. A TB case was defined as a TB suspect with at least one positive sputum
      smear. We calculated adjusted odds ratios with 95% confidence intervals for the
      association between smear positivity and health service and patient's
      characteristics. RESULTS:   Smear positivity was 7.3% (321/4376). Of the 4376
      adults submitting sputa, 55.3% (2418) reported cough for <14 days. In this group,
      smear microscopy yielded 3.2% (78/2418) positive results vs. 12.4% (243/1958) in
      patients coughing for 14 or more days. Having cough for >2 weeks, being referred
      by health care staff, attending a secondary-level health care facility, male sex
      and age between 15 and 44 years were independent determinants of smear
      positivity. CONCLUSIONS: Routine case detection yields a low proportion of smear
      positive cases because of the inclusion of a high proportion of patients without
      cough or coughing for <2 weeks. Adherence to the national TB control programme
      guidelines on the selection of TB suspects would have a positive impact on the
      smear positivity rate, reduce laboratory costs and workload and possibly improve
      the reading quality of smear microscopy.

PMID- 21087376
TI  - Immunovirological outcomes and resistance patterns at 4 years of antiretroviral
      therapy use in HIV-infected patients in Cambodia.
AB  - OBJECTIVES: To report immunovirological outcomes and resistance patterns in
      adults treated with triple combination antiretroviral therapy (cART) for 4 years
      in an HIV programme of Phnom Penh, Cambodia. METHODS: It is a longitudinal study
      and cross-sectional evaluation of adults receiving cART for 4 years. CD4 cell
      counts and HIV-1 RNA were quantified, and resistance patterns were determined.
      Drug-related toxicity was assessed by clinicians and through laboratory testing.
      RESULTS: After 4 years of cART start, the cumulative probability of retention in
      care was 0.80 and survival among patients not lost to follow-up was 0.85. A total
      of 349 patients (98% of eligible) participated in the cross-sectional evaluation.
      Ninety per cent were receiving first-line therapy, 29% stavudine- and 58%
      zidovudine-containing regimens (compared with 94% and 3% at cART initiation).
      Ninety-three per cent of patients were clinically asymptomatic, and severe
      lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively.
      Good treatment adherence was reported by 83% of patients. Median CD4 T-cell count
      was 410 cells/MUl [IQR 290-511], and 90% of patients had >200 cells/MUl. Only 15
      (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/MUl), five
      had thymidine analogue mutations, and nine were resistant to two drug classes. In
      an intention-to-treat analysis, 26.1% (95% CI 22.0-30.5) of patients had failed
      first-line therapy. CONCLUSIONS: In this Cambodian cohort of adults who started
      cART at an advanced stage of HIV disease, we observed good clinical and
      immunovirological outcomes and self-reported treatment adherence at 4 years of
      therapy.

PMID- 21087378
TI  - Genetic variability in Plasmodium vivax aldolase gene in Korean isolates and the
      sensitivity of the Binax Now malaria test.
AB  - Introduction of rapid malaria diagnostic tests (RDT) initiated numerous field
      evaluations in various epidemiologic settings. But the efficiency of some RTD
      kits based on aldolase raised reservations for direct implementation of RDT into
      clinical settings. We performed Binax Now malaria test in 84 Korean Plasmodium
      vivax isolates and compared it with the traditional Giemsa stain microscopy test
      as the reference standard. The sensitivity of Binax Now was 62.0% for P. vivax
      cases (52/84, 95% CI 51.2-71.6%) with 100.0% specificity (50/50, 95% confidence
      interval 92.9-100%). After the aldolase gene sequence analysis of 84 isolates,
      two synonymous mutations in aldolase gene were identified in both Binax Now
      positive and negative samples. No significant association between the mutations
      and Binax Now malaria tests was found. Thus, the genetic variability would not
      explain the poor performance of P. vivax RDTs by detecting aldolase in ROK
      isolates.

PMID- 21087379
TI  - Would rational use of antibiotics be compromised in the era of test-based
      management of malaria?

PMID- 21087377
TI  - Long-term effectiveness and safety of didanosine combined with lamivudine and
      efavirenz or nevirapine in antiretroviral-naive patients: a 9-year cohort study
      in Senegal.
AB  - OBJECTIVE: The use of didanosine (ddI) in first-line antiretroviral therapy has
      been recently promoted for resource-limited settings. We therefore compared the
      long-term effectiveness and safety of the regimen combining ddI, lamivudine, and
      efavirenz or nevirapine with that of the WHO-recommended regimen of zidovudine
      (ZDV), lamivudine, and efavirenz or nevirapine in antiretroviral-naive patients
      in Senegal. METHODS: Observational cohort study of patients enrolled between
      January 2000 and April 2002 in the Senegalese antiretroviral drug access
      initiative. Multivariate analyses were performed to compare, between the ddI and
      ZDV groups, the proportion of patients with a viral load <500 copies/ml during
      follow-up; the increase in the CD4 cell count; survival; treatment changes and
      severe adverse events. RESULTS: Of 151 patients, 71 received the ddI-based
      treatment and 80 received the ZDV-based treatment. Throughout follow-up, 80-95%
      of patients had a viral load below 500 copies/ml in both the ddI and ZDV groups
      (P = 0.5). The CD4 cell count increased after treatment initiation from 176 to
      497 cells/mm(3) in the ddI group and from 176 to 567 cells/mm(3) in the ZDV group
      (P > 0.3). The rate of death tended to be higher in the ddI group (P = 0.06). ddI
      was less commonly discontinued than ZDV (P = 0.03). CONCLUSION: The combination
      of ddI, lamivudine, and efavirenz or nevirapine resulted in sustained viral
      suppression and immunological recovery.

PMID- 21087380
TI  - Functional landscape heterogeneity and animal biodiversity in agricultural
      landscapes.
AB  - Biodiversity in agricultural landscapes can be increased with conversion of some
      production lands into 'more-natural'- unmanaged or extensively managed - lands.
      However, it remains unknown to what extent biodiversity can be enhanced by
      altering landscape pattern without reducing agricultural production. We propose a
      framework for this problem, considering separately compositional heterogeneity
      (the number and proportions of different cover types) and configurational
      heterogeneity (the spatial arrangement of cover types). Cover type classification
      and mapping is based on species requirements, such as feeding and nesting,
      resulting in measures of 'functional landscape heterogeneity'. We then identify
      three important questions: does biodiversity increase with (1) increasing
      heterogeneity of the more-natural areas, (2) increasing compositional
      heterogeneity of production cover types and (3) increasing configurational
      heterogeneity of production cover types? We discuss approaches for addressing
      these questions. Such studies should have high priority because biodiversity
      protection globally depends increasingly on maintaining biodiversity in human
      dominated landscapes.

PMID- 21087381
TI  - Occurrence, genes and expression of the W/Se-containing class II benzoyl-coenzyme
      A reductases in anaerobic bacteria.
AB  - Benzoyl-coenzyme A (CoA) reductases (BCRs) are key enzymes in the anaerobic
      degradation of aromatic compounds and catalyse the reductive dearomatization of
      benzoyl-CoA to cyclohexa-1,5-dienoyl-1-carboxyl-CoA. Class I BCRs are ATP
      dependent FeS enzymes, whereas class II BCRs are supposed to be ATP-independent
      and contain W, FeS clusters, and most probably selenocysteine. The active site
      components of a putative eight subunit class II BCR, BamBCDEFGHI, were recently
      characterized in Geobacter metallireducens. In this organism bamB was identified
      as structural gene for the W-containing active site subunit; bamF was predicted
      to code for a selenocysteine containing electron transfer subunit. In this work
      the occurrence and expression of BCRs in a number of anaerobic, aromatic compound
      degrading model microorganisms was investigated with a focus on the BamB and BamF
      components. Benzoate-induced class II BCR in vitro activities were determined in
      the soluble protein fraction in all obligately anaerobic bacteria tested. Where
      applicable, the results were in agreement with Western blot analysis using BamB
      targeting antibodies. By establishing a specific bamB targeting PCR assay, bamB
      homologues were identified in all tested obligately anaerobic bacteria with the
      capacity to degrade aromatic compounds; a number of bamB sequences from Gram
      negative/positive sulfate-reducing bacteria were newly sequenced. In several
      organisms at least two bamB paralogues per genome were identified; however, in
      nearly all cases only one of them was transcribed during growth on an aromatic
      substrate. These benzoate-induced bamB genes are proposed to code for the active
      site subunit of class II BCRs; the major part of them group into a phylogenetic
      subcluster within the bamB homologues. Results from in silico analysis suggested
      that all class II BCRs contain selenocysteine in the BamF, and in many cases also
      in the BamE subunit. The results obtained indicate that the distribution of the
      two classes of BCRs in anaerobic bacteria appears to be strictly ruled by the
      available free energy from the oxidation of the aromatic carbon source rather
      than by phylogenetic relationships.

PMID- 21087382
TI  - Root exudates modify bacterial diversity of phenanthrene degraders in PAH
      polluted soil but not phenanthrene degradation rates.
AB  - To determine whether the diversity of phenanthrene-degrading bacteria in an aged
      polycyclic aromatic hydrocarbon (PAH) contaminated soil is affected by the
      addition of plant root exudates, DNA stable isotope probing (SIP) was used.
      Microcosms of soil with and without addition of ryegrass exudates and with 13C
      labelled phenanthrene (PHE) were monitored over 12 days. PHE degradation was
      slightly delayed in the presence of added exudate after 4 days of incubation.
      After 12 days, 68% of added PHE disappeared both with and without exudate. Carbon
      balance using isotopic analyses indicated that a part of the 13C-PHE was not
      totally mineralized as 13CO2 but unidentified 13C-compounds (i.e. 13C-PHE or 13C
      labelled metabolites) were trapped into the soil matrix. Temporal thermal
      gradient gel electrophoresis (TTGE) analyses of 16S rRNA genes were performed on
      recovered 13C-enriched DNA fractions. 16S rRNA gene banding showed the impact of
      root exudates on diversity of PHE-degrading bacteria. With PHE as a fresh sole
      carbon source, Pseudoxanthomonas sp. and Microbacterium sp. were the major PHE
      degraders, while in the presence of exudates, Pseudomonas sp. and Arthrobacter
      sp. were favoured. These two different PHE-degrading bacterial populations were
      also distinguished through detection of PAH-ring hydroxylating dioxygenase (PAH
      RHD(alpha)) genes by real-time PCR. Root exudates favoured the development of a
      higher diversity of bacteria and increased the abundance of bacteria containing
      known PAH-RHD(alpha) genes.

PMID- 21087383
TI  - Cells dispersed from Marinobacter hydrocarbonoclasticus SP17 biofilm exhibit a
      specific protein profile associated with a higher ability to reinitiate biofilm
      development at the hexadecane-water interface.
AB  - Biofilm formation by marine hydrocarbonoclastic bacteria is commonly observed and
      has been recognized as an important mechanism for the biodegradation of
      hydrocarbons. In order to colonize new oil-water interfaces, surface-attached
      communities of hydrocarbonoclastic bacteria must release cells into the
      environment. Here we explored the physiology of cells freshly dispersed from a
      biofilm of Marinobacter hydrocarbonoclasticus developing at the hexadecane-water
      interface, by combining proteomic and physiological approaches. The comparison of
      the dispersed cells' proteome with those of biofilm, logarithmic- and stationary
      phase planktonic cells indicated that dispersed cells had lost most of the
      biofilm phenotype and expressed a specific proteome. Two proteins involved in
      cell envelope maturation, DsbA and CtpA, were exclusively detected in dispersed
      cells, suggesting a reshaping of the cell envelopes during biofilm dispersal.
      Furthermore, dispersed cells exhibited a higher affinity for hexadecane and
      initiated more rapidly biofilm formation on hexadecane than the reference
      planktonic cells. Interestingly, storage wax esters were rapidly degraded in
      dispersed cells, suggesting that their observed physiological properties may rely
      on reserve mobilization. Thus, by promoting oil surface colonization, cells
      emigrating from the biofilm could contribute to the success of marine
      hydrocarbonoclastic bacteria in polluted environments.

PMID- 21087385
TI  - Diversity at its best: bacterial taxis.
AB  - Bacterial taxis is one of the most investigated signal transduction mechanisms.
      Studies of taxis have primarily used Escherichia coli and Salmonella as model
      organism. However, more recent studies of other bacterial species revealed a
      significant diversity in the chemotaxis mechanisms which are reviewed here.
      Differences include the genomic abundance, size and topology of chemoreceptors,
      the mode of signal binding, the presence of additional cytoplasmic signal
      transduction proteins or the motor mechanism. This diversity of chemotactic
      mechanisms is partly due to the diverse nature of input signals. However, the
      physiological reasons for the majority of differences in the taxis systems are
      poorly understood and its elucidation represents a major research need.

PMID- 21087384
TI  - Molecular biology of surface colonization by Listeria monocytogenes: an
      additional facet of an opportunistic Gram-positive foodborne pathogen.
AB  - The opportunistic and facultative intracellular pathogenic bacterium Listeria
      monocytogenes causes a rare but severe foodborne disease called listeriosis, the
      outcome of which can be fatal. The infection cycle and key virulence factors are
      now well characterized in this species. Nonetheless, this knowledge has not
      prevented the re-emergence of listeriosis, as recently reported in several
      European countries. Listeria monocytogenes is particularly problematic in the
      food industry since it can survive and multiply under conditions frequently used
      for food preservation. Moreover, this foodborne pathogen also forms biofilms,
      which increase its persistence and resistance in industrial production lines,
      leading to contamination of food products. Significant differences have been
      reported regarding the ability of different isolates to form biofilms, but no
      clear correlation can be established with serovars or lineages. The architecture
      of listerial biofilms varies greatly from one strain to another as it ranges from
      bacterial monolayers to the most recently described network of knitted chains.
      While the role of polysaccharides as part of the extracellular matrix
      contributing to listerial biofilm formation remains elusive, the importance of
      eDNA has been demonstrated. The involvement of flagella in biofilm formation has
      also been pointed out, but their exact role in the process remains to be
      clarified because of conflicting results. Two cell-cell communication systems
      LuxS and Agr have been shown to take part in the regulation of biofilm formation.
      Several additional molecular determinants have been identified by functional
      genetic analyses, such as the (p)ppGpp synthetase RelA and more recently BapL.
      Future directions and questions about the molecular mechanisms of biofilm
      formation in L. monocytogenes are further discussed, such as correlation between
      clonal complexes as revealed by MLST and biofilm formation, the swarming over
      swimming regulation hypothesis regarding the role of the flagella, and the
      involvement of microbial surface components recognizing adhesive matrix molecules
      in the colonization of abiotic and biotic surfaces.

PMID- 21087386
TI  - Mucosectomy and stapled pouch-anal anastomosis in familial adenomatous polyposis.
AB  - AIM: In familial adenomatous polyposis, a restorative proctocolectomy with an
      ileo-anal pouch may be performed either with a mucosectomy and a hand-sewn
      anastomosis or as a stapled anastomosis without a mucosectomy. The disadvantage
      of the former is suboptimal bowel function and the disadvantage of the latter is
      a high risk of recurrent adenomas in the rectal mucosal remnant. METHOD: A
      procedure is presented that combines the advantages of mucosectomy and stapled
      ileo-anal anastomosis. RESULTS: No severe complications were seen in 14 patients.
      After a median follow up of 29 (range 7-144) months, 13 (93%) patients were fully
      continent day and night with a median frequency of defecation of 5 (range 2-8)/24
      h. No adenomas were found at the annual endoscopic follow up. CONCLUSION:
      Mucosectomy with a stapled ileo-anal pouch has few complications. Short-term
      results show good function and a very low risk of recurrent adenoma development.

PMID- 21087387
TI  - Online signal processing of internal anal sphincter activity during pelvic
      autonomic nerve stimulation: a new method to improve the reliability of intra
      operative neuromonitoring signals.
AB  - AIM: Intra-operative neuromonitoring is increasingly applied in several surgical
      disciplines and has been introduced to facilitate pelvic autonomic nerve
      preservation. Nevertheless, it has been considered a questionable tool for the
      minimization of risk, as the results are variable and might be misleading. The
      aim of the present experimental study was to develop an intra-operative
      neuromonitoring system with improved reliability for monitoring pelvic autonomic
      nerve function. METHOD: Fifteen pigs underwent low anterior rectal resection with
      pelvic autonomic nerve preservation. Intra-operative neuromonitoring was
      performed under autonomic nerve stimulation with observation of electromyographic
      signals of the internal anal sphincter and bladder manometry. As the internal
      anal sphincter frequency spectrum during stimulation was found to be mainly in
      the range of 5-20 Hz, intra-operative neuromonitoring signals were
      postoperatively processed by implementation of matching band pass filters.
      RESULTS: In 10 preliminary experiments, signal processing was performed offline
      in the postoperative analysis. Of 163 stimulations intra-operatively assessed by
      the surgeon as positive responses, 135 (83%) were confirmed after signal
      processing. In the following five consecutive experiments intra-operative online
      signal processing was realized and demonstrated reliable intra-operative
      neuromonitoring signals of internal anal sphincter activity with significant
      increase during pelvic autonomic nerve stimulation [0.5 MUV (interquartile range
      = 0.3-0.7) vs 4.8 MUV (interquartile range = 2.5-7.5); P < 0.001]. CONCLUSION:
      Online signal processing of internal anal sphincter activity aids reliable
      identification of pelvic autonomic nerves with potential for improvement of intra
      operative neuromonitoring in pelvic surgery.

PMID- 21087388
TI  - Laparoscopic surgery for recurrent ileocolic Crohn's disease is as safe and
      effective as primary resection.
AB  - AIM: The safety and short-term outcome of laparoscopic surgery for recurrent
      ileocolic Crohn's disease was compared with the outcome following primary
      resection. METHOD: Between June 2002 and June 2010, 59 consecutive unselected
      patients (30 of whom had recurrent disease) underwent laparoscopic ileocolic
      resection. Four primary resections and one revision were performed as a single
      incision laparoscopic surgery (SILS) procedure. RESULTS: There was no difference
      between the two groups in terms of age, body mass index, American Society of
      Anesthesiology (ASA) grade or the presence or absence of fistulating disease. The
      median operating time was significantly longer for the revision group (125 min vs
      85 min; P < 0.001). The rate of conversion was 8.5%, morbidity was 20% and
      mortality was 0% (P = not significant between groups). Risk factors for
      conversion included a complex fistula, fibrosis and the need to carry out
      multiple stricturoplasty. Patients in whom surgery was converted had a longer
      hospital stay and a higher morbidity (40%). The median hospital stay was 3 days,
      the return to theatre rate was 5% and the re-admission rate was 5% (P = not
      significant between groups). CONCLUSION: Laparoscopic surgery for recurrent
      ileocolic Crohn's disease is safe and can lead to significant short-term benefit,
      including earlier discharge. Conversion increases the length of stay in hospital
      and the overall morbidity.

PMID- 21087389
TI  - Renal cell carcinoma: stage, grade and histology migration over the last 15 years
      in a large Australian surgical series.
AB  - OBJECTIVE: * To verify whether migration towards earlier-stage renal cell
      carcinoma (RCC), which has been observed in the USA over the last decade, also
      applies to Australia. PATIENTS AND METHODS: * Between January 1993 and December
      2007, 547 nephrectomies performed in public and private hospitals in western
      Sydney were analysed from a retrospectively collected database. * Data were
      divided into three consecutive time groups. * Tumour-node-metastasis (TNM) stage
      as well as patient demographics, size, grade and histology of tumours and
      proportion of benign tumours were also assessed. RESULTS: * In all, 499
      nephrectomies were performed for RCC. The median age was 62 years, with a
      male:female ratio of 1.9 : 1. Similarly sized tumours were identified in each
      time group [group 1 (1993-1997), 54.8 mm; group 2 (1998-2002), 52.0 mm; group 3
      (2003-2007), 52.2 mm, P= 0.6]. * Pathological stage II disease decreased from
      18.1 to 11.1%, but stage III disease showed an increase from 13.9 to 21.5% over
      that time period (P= 0.02). * The proportion of stage I and stage IV disease has
      remained relatively the same. There has been a statistically significant upward
      histological migration for the papillary subtype from 1.3 to 10.2% (P= 0.01). *
      There has also been an increasing representation of Fuhrman grade III tumours
      over time, from 17.6 to 30.8%, and a decreasing proportion of Fuhrman grade I
      tumours from 16.2 to 7.1% (P= 0.03). * There was a decrease in the incidence of
      benign tumours originally thought to be malignant on preoperative investigations,
      from 10% in group 1 to 4% in group 3 (P= 0.03). CONCLUSION: * The recent US
      phenomenon of migration towards earlier-stage, smaller RCCs as well as increased
      representation of benign tumours was not observed in the present study. The
      results of the present study, however, show an upward histological migration for
      papillary RCCs and an increasing representation of more aggressive Fuhrman grade
      III tumours.

PMID- 21087390
TI  - Trends in the care of radical prostatectomy in the United States from 2003 to
      2006.
AB  - OBJECTIVE: * o determine differences in surgical outcomes by surgical approach
      during a period of rapid adoption of minimally invasive surgical approaches in
      radical prostatectomy. PATIENTS AND METHODS: * We identified 19 542 men
      undergoing minimally invasive (MIRP), perineal (PRP), and retropubic (RRP)
      radical prostatectomy from 2003 to 2006 from the MarketScan(r) Medstat database,
      a national employer-based administrative database. * We assessed for temporal
      trends in perioperative complications, use of postoperative cystography and
      anastomotic strictures by surgical approach. RESULTS: * Between 2003 and 2006,
      MIRP use increased 33.6% vs 31.8% and 1.7% decreases in RRP and PRP,
      respectively. During the 4-year study, median length of stay for MIRP decreased
      from 2.0 to 1.0 day (P = 0.004) and overall perioperative complications decreased
      from 13.8 to 10.7%, (P = 0.023). * These findings were driven by reductions in
      genitourinary complications (3.3 to 2.5%, P = 0.049), miscellaneous surgical
      complications (3.6 to 2.3%, P = 0.006) and intestinal injury (1.5 to 0.1%, P=
      0.009). * Median length of stay for RRP decreased from 3.2 to 2.9 days, (P <
      0.001), overall perioperative complications decreased from 18.1 to 14.6%, (P =
      0.007), because of reductions in both wound/bleeding complications (2.0 to 1.1%,
      P = 0.002) and heterologous blood transfusions. * Men undergoing MIRP vs RRP were
      less likely to have perioperative complications (12.5 vs 17.1%, P < 0.001), blood
      transfusions (1.5 vs 8.9%, P < 0.001) and anastomotic strictures (6.3 vs 12.8%, P
      < 0.001), and they had shorter mean lengths of stay (1.8 vs 3.1 days, P < 0.001)
      during the study period. CONCLUSION: * The increased use of MIRP corresponds with
      a decreasing trend for complications, blood transfusions, lengths of stay and
      need for reoperation. Additionally, MIRP was found to have fewer associated
      complications compared with men undergoing open procedures. Further study is
      needed to assess the impact of tumour characteristics and surgeon volume on these
      perioperative outcomes as well as effects on long-term cancer control.

PMID- 21087391
TI  - Renal nephrometry score is associated with urine leak after partial nephrectomy.
AB  - OBJECTIVE: * To determine if the RENAL nephrometry score is associated with urine
      leak after partial nephrectomy for tumours <= 7 cm. PATIENTS AND METHODS: *
      Thirty-one patients who developed urine leak after partial nephrectomy between
      1998 and 2006 were identified. Each patient was individually matched (1 : 4 by
      age, gender and surgery date) to 124 patients who had undergone partial
      nephrectomy but without urine leak. * Associations of RENAL nephrometry scores
      and each component of the score (Radius; Endophytic; Nearness to collecting
      system; and Location) with urine leak were evaluated using conditional logistic
      regression. RESULTS: * Mean tumour size for the 31 patients who developed urine
      leak was 3.4 cm (median 3.5; range 1.5-5.9). Mean RENAL score was 8 (median 8;
      range 5-11). * Each unit increase in RENAL score was associated with a 35%
      increased odds of urine leak (OR 1.35; 95% CI 1.08-1.69; P= 0.009). * On
      multivariable analysis, tumours that were <50% exophytic (OR 16.65; 95% CI 2.75
      100.71; P= 0.002), completely endophytic (OR 17.02; 95% CI 2.88-100.55; P=
      0.002), or located at the renal pole (OR 4.34; 95% CI 1.30-14.53; P= 0.017) were
      associated with urine leak. * If the score attributed to tumour location was
      reversed (polar location given a higher score), each unit increase in RENAL score
      was associated with an 89% increased odds of urine leak (OR 1.89; 95% CI 1.40
      2.55; P < 0.001). CONCLUSION: * The RENAL nephrometry score is associated with
      risk of urine leak after partial nephrectomy. When assessing risk of urine leak,
      reversal of the score attributed to tumour location may improve risk prediction.

PMID- 21087392
TI  - Temporal diabetes and diuresis-induced alteration of nerves and vasculature of
      the urinary bladder in the rat.
AB  - OBJECTIVE: * To characterize the temporal changes of the nerves and vasculature
      of the bladder in diabetic rats. MATERIALS AND METHODS: * A total of 36 Sprague
      Dawley rats were divided into three groups: streptozotocin-induced diabetics, 5%
      sucrose-induced diuretics and age-matched controls. * The characteristics of the
      nerves and vasculature in the equatorial cross-sectional areas of the bladder
      were examined by immunofluorescence staining of their specific markers,
      neurofilament 200 (NF200) and CD31, at 1, 9 or 20 weeks after induction. * The
      distributions of the nerves and blood vessels were observed and the densities
      were quantified. RESULTS: * Diabetes caused a significant reduction in body
      weight. Bladder weight increased in diabetic and diuretic rats, but not in
      controls. * The total cross-sectional wall area and detrusor muscle area at the
      equatorial midline were greater in bladders of diabetic and diuretic rats than in
      controls. * Neurofilament 200-immunoreactive (NF200-IR) nerves were mainly
      distributed in the detrusor muscle. CD31-immunoreactive blood vessels were mainly
      distributed in the mucosa/submucosa. * There were no significant differences in
      the NF200-IR nerve terminal area among control, diabetic and diuretic groups.
      However nerve density was decreased at 9 and 20 weeks in the muscle, and at 20
      weeks in the mucosa/submucosa in diabetic and diuretic animals. * Blood vessel
      density decreased in the diabetic and diuretic groups at 20 weeks in the muscle.
      CONCLUSIONS: * Diabetes induced time-dependent changes in the density of the
      nerves and vasculature in the bladder tissues. * Diabetes-related polyuria plays
      an important role in these changes.

PMID- 21087394
TI  - Attenuation of bladder overactivity in KIT mutant rats.
AB  - OBJECTIVES: To investigate morphological and physiological findings in the
      bladder of KIT mutant (WsRCWs/Ws) rats to clarify whether the disturbance of KIT
      pathways affects bladder activity. To discuss the potential role of KIT-positive
      interstitial cells of Cajal (ICC)-like cells in the urinary bladder. MATERIALS
      AND METHODS: Reverse transcriptase-polymerase chain reaction and western blotting
      was used to confirm the absence of c-kit mRNA and protein in the bladders of 12
      week-old WsRCWs/Ws rats. Light and transmission electron microscopy was used to
      identify the differences in morphological and ultrastructural characteristics of
      the bladder between WsRCWs/Ws and wild-type (WsRC+/+) rats. The voiding pattern
      of WsRCWs/Ws rats and the effects of cyclophosphamide (CYP) and protamine
      sulphate on bladder function were examined using cystometry. RESULTS: In WsRC+/+
      rats, c-kit mRNA and KIT protein expression were observed in the urinary bladder,
      while they were not detectable in WsRCWs/Ws rats. Deformation of ICC-like cells
      with the collapse of the organelle was not observed in the bladders of WsRCWs/Ws
      rats. Each cystometry variable in WsRCWs/Ws rats was similar to that in WsRC+/+
      rats. The reduction in the intercontraction intervals in WsRCWs/Ws rats with
      chemically (CYP and protamine sulphate) induced cystitis was significantly lower
      than in WsRC+/+ rats (P < 0.05). CONCLUSION: Certain voiding disturbances might
      be associated with impaired KIT signalling in ICC-like cells, therefore, KIT
      could be a candidate target for medical therapy in the future.

PMID- 21087393
TI  - Risk group stratification to predict recurrence after transurethral resection in
      Japanese patients with stage Ta and T1 bladder tumours: validation study on the
      European Association of Urology guidelines.
AB  - OBJECTIVE: * To validate the European Association of Urology (EAU) guidelines on
      risk group stratification to predict recurrence in Japanese patients with stage
      Ta and T1 bladder tumours. PATIENTS AND METHODS: * A cohort of 592 Japanese
      patients who were treated with transurethral resection (TUR) and
      histopathologically diagnosed with Ta and T1 urothelial carcinoma of the bladder
      were enrolled in this retrospective study. * The primary endpoint of the present
      study was recurrence-free survival, and the median follow-up duration was 37
      months in recurrence-free survivors. RESULTS: * Multivariate Cox proportional
      hazards regression analysis showed that the Eastern Cooperative Oncology Group
      performance status (ECOG PS), prior recurrence rate, number of tumours and T
      category were independent predictors of time to recurrence (P < 0.05). According
      to the EAU guidelines for predicting recurrence, the vast majority of Japanese
      patients were classified into intermediate risk. * The intermediate-risk patients
      were further divided into intermediate-low-risk and intermediate-high-risk
      subgroups based on the European Organization for Research and Treatment of Cancer
      risk table, and a significant difference in the recurrence-free survival rates
      was found between these subgroups (P < 0.001). * It was also found that patients
      with high risk combined with intermediate-high risk had significantly poorer
      recurrence-free survival rates than those with low risk combined with
      intermediate-low risk (P < 0.001). CONCLUSIONS: * This is the first report on the
      ECOG PS as a potentially useful predictor for bladder tumour recurrence. * The
      risk group stratification of the EAU guidelines for recurrence might not be
      applicable to Japanese patients with Ta and T1 bladder tumours, but the subgroup
      classification of intermediate risk could be appropriate.

PMID- 21087395
TI  - Radical prostatectomy for cT3-4 disease: an evaluation of the pathological
      outcomes and patterns of care for adjuvant radiation in a national cohort.
AB  - OBJECTIVE: * To use the Surveillance, Epidemiology and End Results Database to
      evaluate the pathological outcomes for patients with clinically staged T3-4
      disease who undergo radical prostatectomy and to analyze whether these patients
      are receiving adjuvant radiation. PATIENTS AND METHODS: * We identified patients
      who were clinically staged as having T3-4N0M0 prostate cancer and underwent
      radical prostatectomy between 2004 and 2006. Clinical data regarding preoperative
      prostate-specific antigen, as well as pathological Gleason score, were also
      collected. * Descriptive analyses were performed regarding the pathological
      extent of disease for these patients. * Logistic regression analysis was
      performed to identify unadjusted and adjusted predictors of radiation use for
      those with non-organ-confined disease or positive margins. RESULTS: * A total of
      718 patients were identified. Of these, 10.2% had organ-confined disease (8.1%
      with negative margins and 2.1% with positive margins). The median number of lymph
      nodes removed was three, with 9.9% of patients having pathologically positive
      lymph nodes. * The clinical accuracy of staging was found to be 81.4% for T3a,
      77.4% for T3b and 70.1% for T4. Of those who had non-organ-confined disease or
      positive margins pathologically, 21.1% received adjuvant radiation. Logistic
      regression analysis revealed that those with Gleason 8-10 disease were most
      likely to receive adjuvant radiation. CONCLUSIONS: * In this large series from a
      population-based cohort, clinical staging of T3-T4 disease was highly accurate in
      predicting pathological extent, with only 10.2% of patients found to have
      pathological T2 disease. * Most patients with confirmed pathological T3-T4
      disease did not receive adjuvant radiation.

PMID- 21087396
TI  - Reduced cardiac vagal activity in obese children and adolescents.
AB  - OBJECTIVE:   Obese children present with various cardiovascular risk factors
      affecting their future health. In adults, cardiac autonomic function is a major
      risk factor, predicting cardiovascular morbidity and mortality. We hypothesized
      that obese children and adolescents had a lower cardiac vagal activity than lean
      subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS),
      reflecting the dynamic regulation of cardiac vagal function, in large groups of
      obese and lean young individuals. METHODS AND RESULTS:   Cardiac BRS, using the
      sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls)
      and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared
      to both overweight and lean subjects [16+/-7 versus 21+/-9 (P<0.01) and 22+/-10
      ms per mmHg (P<0.0001), respectively]. The differences remained after correcting
      for age, gender and pubertal status. CONCLUSION:   Children with obesity had low
      vagal activity at rest, and there was no gender difference.

PMID- 21087397
TI  - Assessments of skin and tongue microcirculation reveals major changes in porcine
      sepsis.
AB  - AIM:   To examine the relation between central hemodynamics, clinical severity
      and microvascular findings in tongue and skin during sepsis. MATERIALS AND
      METHODS:   Skin and tongue microcirculation was examined using laser Doppler and
      video microscopy techniques before and 200 min after inducing sepsis in pigs
      (n=6) by inactivated Neisseria meningitides and in two control animals. RESULTS: 
      All infected pigs developed clinical signs of sepsis. Pericapillary bleedings
      developed in the tongue in the two pigs with the most severe disease. Capillary
      density increased in the groin skin in infected pigs after 200 min as compared to
      baseline (P<0.02). In the same period, mean capillary flow velocity was reduced
      in groin skin and tongue in septic pigs (P<0.02). At 200 min a fraction of
      capillaries had developed 'no flow' or 'brisk flow', patterns hardly seen at
      baseline. Laser Doppler perfusion was reduced in ear and tongue after 200 min
      (P<0.02 for both). The described pathology was more pronounced in the pigs with
      the most severe sepsis. CONCLUSION:   Capillary bleedings may be used as an early
      indication of severe sepsis. Examination of skin and tongue microcirculations may
      be used to characterize severity of sepsis and possibly to assess effect of
      treatment.

PMID- 21087398
TI  - Iliac crest autogenous bone graft versus alloplastic graft and guided bone
      regeneration in the reconstruction of atrophic maxillae: a 5-year retrospective
      study on cost-effectiveness and clinical outcome.
AB  - BACKGROUND: Reconstruction of the atrophic maxillae with autogenous bone graft
      and jawbone-anchored bridges is a well-proven technique. However, the morbidity
      associated with the concept should not be neglected. Furthermore, the costs for
      such treatment, including general anesthesia and hospital stay, are significant.
      Little data are found in the literature with regard to a cost-benefit approach to
      various treatment alternates. PURPOSE: The aim of this retrospective study was to
      compare from a health-economical and clinical perspective the reconstruction of
      the atrophic maxillae prior to oral implant treatment either with autogenous bone
      grafts harvested from the iliac crest or the use of demineralized freeze-dried
      bone (DFDB) in combination with a thermoplastic carrier (Regeneration
      Technologies Inc., Alachua, FL, USA) and guided bone regeneration (GBR).
      MATERIALS AND METHODS: A total of 26 patients (13 + 13) were selected and matched
      with regard to indication, sex, and age. The study was performed 5 years after
      the completion of the treatment. Implant survival, morbidity, and complications
      were analyzed. Furthermore, a detailed analysis of the total cost for the
      respective treatment modality was performed, including material, costs for staff,
      sick leave, etc. RESULTS: The study revealed no statistical difference with
      regard to implant survival for the respective groups. The average total cost, per
      patient, for the DFDB group was 22.5% of the total cost for a patient treated
      with autogenous bone grafting procedures. CONCLUSIONS: The study concluded that
      reconstruction of atrophic maxillae with a bone substitute material (DFDB) in
      combination with GBR can be performed with an equal treatment outcome and with
      less resources and a significant reduced cost in selected cases compared with
      autogenous bone grafts from the iliac crest.

PMID- 21087400
TI  - Radiculopathy in degenerative lumbar scoliosis: correlation of stenosis with
      relief from selective nerve root steroid injections.
AB  - OBJECTIVE: The purpose is to define the origin of radiculopathy of patients with
      degenerative lumbar scoliosis-stenosis and to assess the correlation between
      percentage of initial radicular leg pain relief with selective nerve root
      injections and lateral canal dimensions. DESIGN: Retrospective clinical study.
      SETTING AND PATIENTS: Thirty-six consecutive patients (average age 72) from Twin
      Cities Spine Center with degenerative lumbar scoliosis (average major curve 25
      degrees ) and radicular symptoms were studied. INTERVENTIONS: Patients underwent
      46 selective steroid injections of nerve roots concordant with clinical
      symptomatology. OUTCOME MEASURES: Radiographic measurements included major and
      lumbosacral curve Cobb angle. Computerized measurements of magnetic resonance
      imaging (MRI) included minimum subarticular height and foramen cross-sectional
      area of the nerve roots that were injected. Initial response from the nerve root
      injections was also rated. RESULTS: Twenty-five percent of nerve root symptoms
      were coming from the major curve, 72.2% from the lumbosacral hemicurve and 2.8%
      from both (P<0.001). The affected nerve roots were more frequently the L4 (34.8%)
      and L5 (28.3%) nerve roots. A total of 71.7% of radicular symptoms were
      originating from the concavity of the curve and 28.7% from the convexity
      (P<0.001). The relief from injections was more than 50% in 75% of the patients at
      15 days postinjection. There was no statistical significant correlation (P>0.05)
      between the lateral canal dimensions and the initial response to injection of
      anesthetic plus steroid injection. CONCLUSIONS: In degenerative lumbar scoliotic
      curves, radicular symptoms are attributed mainly to nerve roots exiting from the
      concavity of the lumbosacral hemicurve. No evidence was found that the rate of
      initial relief from selective nerve root injections correlates with the degree of
      stenosis noted in the MRI.

PMID- 21087399
TI  - Gene expression of inflammation and bone healing in peri-implant crevicular fluid
      after placement and loading of dental implants. A kinetic clinical pilot study
      using quantitative real-time PCR.
AB  - PURPOSE: Early detection of healing complications after placement of dental
      implants is a pressing but elusive goal. This paper proposes a non-invasive
      diagnostic tool for monitoring healing- and peri-implant disease specific genes,
      complementary to clinical evaluations. MATERIAL AND METHODS: Eighteen partially
      edentulous patients were recruited to this pilot study. Three Branemark
      TiUnite(r) implants/patient (Nobel Biocare) were placed in a one-stage procedure.
      Abutments with smooth or rough (TiUnite(r)) surface were placed. The test group
      (n = 9) received fixed bridges (immediate loading), whereas the control group (n
      = 9) implants were loaded 3 months after surgery. In addition to clinical
      measurements, crevicular fluid was collected using paper strips at the implant
      abutments 2, 14, 28, and 90 days postoperative. mRNA was extracted, purified, and
      converted to cDNA. Quantitative PCR assays for IL-1beta, TNF-alpha, Osteocalcin
      (OC), Alkaline Phosphatase (ALP), Cathepsin K, Tartrate Resistant Acid
      Phosphatase, and 18S ribosomal RNA were designed and validated. Relative gene
      expression levels were calculated. RESULTS: One implant was lost in the control
      group and three in the test group. In one test patient, one implant showed
      lowered stability after 2 to 4 weeks and was unloaded. Later implant stability
      improved which allowed for loading after 3 to 4 months. TNF-alpha and ALP most
      commonly showed correlation with clinical parameters followed by IL-1beta and OC.
      The strongest correlation was found for TNF-alpha with clinical complications at
      2 and 14 days (p = .01/r = -048, and p = .0004/r = -0.56, respectively; test and
      control groups together). In some cases, gene expression predicted clinical
      complications (TNF-alpha, ALP, CK). CONCLUSION: This study is based on samples
      from few individuals; still, some genes showed correlation with clinical
      findings. Further studies are needed to refine and optimize the sampling process,
      to find the appropriate panel, and to validate gene expression for monitoring
      implant healing.

PMID- 21087401
TI  - Preclinic group education sessions reduce waiting times and costs at public pain
      medicine units.
AB  - OBJECTIVE: To assess the effects of preclinic group education sessions and system
      redesign on tertiary pain medicine units and patient outcomes. DESIGN:
      Prospective cohort study. SETTING: Two public hospital multidisciplinary pain
      medicine units. PATIENTS: People with persistent pain. INTERVENTIONS: A system
      redesign from a "traditional" model (initial individual medical appointments) to
      a model that delivers group education sessions prior to individual appointments.
      Based on Patient Triage Questionnaires patients were scheduled to attend Self
      Training Educative Pain Sessions (STEPS), a two day eight hour group education
      program, followed by optional patient-initiated clinic appointments. OUTCOME
      MEASURES: Number of patients completing STEPS who subsequently requested
      individual outpatient clinic appointment(s); wait-times; unit cost per new
      patient referred; recurrent health care utilization; patient satisfaction; Global
      Perceived Impression of Change (GPIC); and utilized pain management strategies.
      RESULTS: Following STEPS 48% of attendees requested individual outpatient
      appointments. Wait times reduced from 105.6 to 16.1 weeks at one pain unit and
      37.3 to 15.2 weeks at the second. Unit cost per new patient appointed reduced
      from $1,805 Australian Dollars (AUD) to AUD$541 (for STEPS). At 3 months,
      patients scored their satisfaction with "the treatment received for their pain"
      more positively than at baseline (change score=0.88; P=0.0003), GPIC improved
      (change score=0.46; P<0.0001) and mean number of active strategies utilized
      increased by 4.12 per patient (P=0.0004). CONCLUSIONS: The introduction of STEPS
      was associated with reduced wait-times and costs at public pain medicine units
      and increased both the use of active pain management strategies and patient
      satisfaction.

PMID- 21087402
TI  - Pain catastrophizing and pain coping among methadone-maintained patients.
AB  - OBJECTIVE: The aim of this study was to examine the association of pain
      catastrophizing and pain coping strategies with characteristic pain intensity (an
      average of worst, least, and typical pain intensity in the past week) and recent
      pain-related disability (an average of three measures of past week pain
      interference) in opioid-dependent patients enrolled in a methadone maintenance
      treatment program (MMTP) who reported recent pain. DESIGN: Cross-sectional
      survey. PATIENTS: One hundred and eight MMTP patients who reported recent pain.
      MEASURES: Participants completed measures of demographics, pain status (i.e.,
      "chronic severe pain" [pain lasting at least 6 months with at least moderate pain
      intensity or significant pain interference in the past week] vs "some pain" [pain
      in the past week not meeting the threshold of chronic severe pain]),
      characteristic pain intensity, recent pain-related disability, somatization,
      depression, catastrophizing, and pain coping strategies. RESULTS:  
      Catastrophizing explained a significant proportion of the variance in
      characteristic pain intensity (14%) and recent pain-related disability (11%)
      after controlling for demographics, pain status, somatization, and depression.
      Mirroring the findings of studies of non-opioid-dependent chronic pain patients,
      greater catastrophizing was associated with greater pain intensity and increases
      in recent pain-related disability. On average, the "chronic severe pain" group
      reported higher levels of catastrophizing than the "some pain" group. CONCLUSION:
      Consistent with studies of patients with chronic pain who are not opioid
      dependent, our findings emphasize the importance of assessing and addressing
      catastrophizing in MMTP patients with pain.

PMID- 21087404
TI  - Deep breathing treatment for idiopathic trigeminal neuralgia.

PMID- 21087405
TI  - Fear of movement, quality of life, and self-reported disability in obese patients
      with chronic lumbar pain.
AB  - OBJECTIVE: To compare fear of movement between obese and non-obese individuals
      seeking therapy for chronic low back pain and to examine whether fear of movement
      predicted disability due to back pain, self-reported walking disability, and
      flexibility. DESIGN: This was a cross-sectional study. SETTING: Outpatient
      physical therapy clinic associated with a tertiary care hospital. PATIENTS:
      Patients with chronic low back pain (N=192; 48.2+/-18.8 years) were stratified
      into obese (average body mass index [BMI] 36.9+/-7.1 kg/m(2) ) or non-obese
      status (average BMI 24.5+/-3.4 kg/m(2) ). OUTCOME MEASURES: The Tampa Scale of
      Kinesiophobia (TSK), Short-Form 8 (SF-8), and Oswestry Disability Survey results
      were main outcome measures. METHODS: Retrospective review of medical charts was
      performed. Hierarchical regression modeling determined the contribution of TSK
      scores to the variance of self-reported disability with walking, overall Oswestry
      score, and flexibility. RESULTS: TSK scores were higher in obese than non-obese
      patients (26.2+/-7.5 vs 23.9+/-6.8 points; P=0.032). The SF-8 physical and mental
      subscores were 6-10% lower in the obese than non-obese patients. Oswestry survey
      scores were higher in the obese patients (40.6 vs 31.6 points; P<0.001). TSK
      scores contributed to self-reported disability with walking and Oswestry
      disability score (both P<0.001), but not flexibility. CONCLUSIONS: Among obese
      patients with chronic lumbar pain, pain-related fear of movement enhanced
      prediction of self-reported disability with walking and overall Oswestry scores.
      The TSK might be a useful clinical assessment to identify obese patients at
      higher risk for future low back disability.

PMID- 21087406
TI  - A longitudinal assessment of painful diabetic peripheral neuropathy on health
      status, productivity, and health care utilization and cost.
AB  - OBJECTIVE: The aim of the current study was to examine the health outcomes of
      patients suffering from painful diabetic peripheral neuropathy (pDPN) over a 3
      year period, relative to patients with diabetes but without neuropathic pain and
      controls. DESIGN: The current study included participants who completed three
      consecutive waves of the National Health and Wellness Survey (2006-2008). These
      participants were categorized into one of three groups: those with pDPN (N=290),
      those with diabetes but without pDPN ("diabetes without pDPN group"; N=1,037),
      and those not diagnosed with diabetes ("control group"; N=8,162). OUTCOME
      MEASURES: Health status (Short Form-12v2), work productivity (Work Productivity
      and Activity Impairment Questionnaire), and resource use were examined with
      repeated-measures models adjusting for demographic and clinical factors. RESULTS:
      The pDPN group reported significantly lower levels of physical quality of life.
      Moreover, physical quality of life scores for the pDPN group decreased at a
      significantly faster rate over a 3-year period relative to other groups. In
      addition, the pDPN patients reported significantly higher levels of impairment of
      work productivity and activity, greater resource use, and higher total 3-year per
      patient costs. CONCLUSIONS: Confirming and expanding upon the literature, our
      results indicate a significantly worse trajectory of quality of life outcomes
      over time and long-term increased total costs for pDPN patients relative to non
      pDPN diabetes patients and controls.

PMID- 21087403
TI  - A multicenter, randomized, double-blind, controlled study of NGX-4010, a high
      concentration capsaicin patch, for the treatment of postherpetic neuralgia.
AB  - OBJECTIVES: To confirm the efficacy, tolerability, and safety of NGX-4010, an 8%
      capsaicin dermal patch (capsaicin 640 ug/cm(2) ), in patients with postherpetic
      neuralgia (PHN). PHN is a chronic pain disorder that can be difficult to treat
      and for which current treatment options are often limited by poor tolerability.
      DESIGN: A total of 418 patients were randomized to receive a single 60-minute
      application of NGX-4010 or a 0.04% capsaicin control patch (3.2 ug/cm(2) ) in a
      multicenter, double-blind, confirmatory, phase 3 study. PATIENTS: Patients were
      18-90 years old with a diagnosis of PHN, pain for at least 6 months, and an
      average baseline Numeric Pain Rating Scale (NPRS) score of 3-9. OUTCOME MEASURES:
      The primary efficacy end point was the percentage change in NPRS score from
      baseline to weeks 2-8. RESULTS: NGX-4010 recipients had a significantly greater
      mean reduction from baseline in pain during weeks 2-8 compared with the control
      group (32.0% vs 24.4%; P=0.011). A >= 30% reduction in mean NPRS scores was
      achieved in 46% of NGX-4010 recipients compared with 34% of controls (P=0.02).
      Pain was significantly lower in NGX-4010 recipients than controls by week 2, and
      greater pain reduction was maintained throughout the remaining 12-week study
      period. Most treatment-emergent adverse events were application site specific
      (notably erythema and pain), transient, and generally mild to moderate in
      severity. CONCLUSIONS: In patients with PHN, a single 60-minute application of
      NGX-4010 produced significant reduction in pain that was maintained over a 12
      week period.

PMID- 21087407
TI  - Predictors of homicide-suicide affirmation in acute and chronic pain patients.
AB  - OBJECTIVES: 1) Determine and compare prevalence for homicide-suicide (H-S)
      affirmation in community non-patients (N=478), community patients (N=158), acute
      pain patients (APPs; N=326), and chronic pain patients (CPPs; N=341); and 2)
      Develop H-S predictor models in APPs and CPPs. DESIGN: A large set of items
      containing the H-S item was administered to the above groups, who were compared
      statistically for H-S endorsement. APPs and CPPs affirming the H-S item were
      compared with those not affirming on all available variables including the
      Battery for Health Improvement (BHI 2) with significant variables (P<= 0.001)
      utilized in predictor models for H-S in APPs and CPPs. SETTING: Community plus
      rehabilitation facilities. RESULTS: The above population groups affirmed the H-S
      item according to the following percentages: healthy community 1.88%, community
      patients 3.16%, rehabilitation patients without pain 3.64%, rehabilitation AAPs
      3.99%, and rehabilitation CPPs 4.40%. For both APPs and CPPs, the H-S item was
      significantly correlated with some suicidality items and some homicide items. The
      model for APPs identified "having a suicide plan" as being predictive of H-S
      affirmation. For CPPs, the items of having thoughts of revenge killing, being
      motivated to seek revenge without any verbal warning, and the Doctor
      Dissatisfaction Scale of the BHI 2 predicted H-S affirmation. The APPs model
      classified 96% of the APPs correctly, while the CPPs model classified 97% of the
      CPPs correctly. These predictor rates, however, were no better than the base
      rate. CONCLUSION: The prevalence of H-S affirmation within APPs and CPPs is not
      insignificant. The APPs predictor model points to a close association between H-S
      affirmation and suicidality. The CPPs model indicates that there is a close
      association between H-S affirmation, and anger/hostility and anger directed at
      physicians. These results, however, should not lead to the belief that CPPs are
      at greater risk for actual H-S completion for the following reasons: 1) H-S is an
      extremely rare event; and 2) predictive validity of the H-S item for actual H-S
      completion has not been determined.

PMID- 21087409
TI  - Epidural blood patch for postdural puncture positional vertigo.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report an unusual case of refractory
      positional vertigo without headache that developed after the placement of an
      epidural catheter for postoperative pain and that was treated with an epidural
      blood patch. SUMMARY OF THE BACKGROUND DATA:   Although it is common practice to
      use epidural blood patch (EBP) to treat positional headache from postdural
      puncture (PDP), the literature is limited to one letter to the editor describing
      PDP positional vertigo treated with EBP. METHODS: Description of a clinical case.
      RESULTS: Here we present a case where the patient presented with the complaint of
      vertigo without headache and had a characteristic onset with upright position and
      marked relief when lying down. The patient received an EBP with complete
      resolution of her symptoms. CONCLUSIONS: This case illustrates patient can
      present with an isolated symptom such as dizziness without headache after PDP.
      The patient received an EBP with complete resolution of her symptom of postdural
      dizziness.

PMID- 21087408
TI  - Toward more useful pressure-controlled discography: in vitro evaluation of
      injection speed, sensor location, and tube length.
AB  - OBJECTIVE: Pressure-controlled manometric discography is used by clinicians to
      evaluate discogenic pain. However, some would improve diagnostic accuracy. The
      goal of this study was to investigate potential confounding factors that might
      affect discographic results. Pressure differences depending on different speed of
      injection, lengths of connecting tubing and locations of sensors were evaluated
      using an in vitro model system. METHODS: Two sets of automated discography
      devices were arranged to record post-syringeal pressure pressures (PSPs) and
      intradiscal pressures (IDPs) in an "air chamber disk model" representing
      intradiscal pressure. PSPs and IDPs were measured simultaneously while varying
      injection speeds, and using intrasyringeal and extrasyringeal pressure sensors
      and contrast medium-filled tubing of different lengths. All pressure/volume
      curves were collected and viewed dynamically, and stored for further analysis.
      RESULTS: At injection speed of 0.1 cc/second, the mean pressure difference (mean
      DeltaP) between PSP and IDP was 38.1 psi. As injection speed was reduced, mean
      DeltaP was proportionally decreased. Mean DeltaP was 5.3 psi at injection speed
      of 0.01 cc/second and 0.7 psi at 0.005 cc/second. Mean DeltaP values were
      significantly higher when pressures were recorded using intrasyringeal sensor: at
      injection speed of 0.1 cc/second, PSP and IDP values were 82.9 and 30.1 psi,
      respectively, compared with 50.6 and 12.5 psi measured by extrasyringeal sensor.
      Mean DeltaP due to increased length of tubing was not significant. CONCLUSION:
      Discography can be better performed with low speed injection (<=0.01 cc/second),
      using an extrasyringeal sensor. Difference of length of connecting tubings did
      not cause significant pressure differences. These data suggest that automated
      discography is a helpful adjunct to improve diagnostic accuracy, due to
      extrasyringeal location of pressure sensor and greater control of injection
      speed.

PMID- 21087410
TI  - Radiofrequency ablation within the first intercoccygeal disk for coccygodynia: a
      case report.
AB  - Interventional procedures for coccydynia (coccygodynia) are limited. This is a
      case report of long-term improvement following radiofrequency ablation (RFA)
      within the 1st intercoccygeal disk. CASE PRESENTATION:   A 44-year-old female
      presented with a 1 year history of coccydynia following a fall. Examination under
      fluoroscopy localized her pain at the disk between the 1st and 2nd coccygeal
      vertebrae. Provocation with needle entry reproduced the patient's pain, and the
      1st intercoccygeal disk was injected with 40 mg of methylprednisolone. This gave
      the patient excellent relief for about 3 weeks. The procedure was repeated at 4
      weeks, providing with the same response. Decision was then made to proceed with
      RFA. Her symptoms were reproduced in response to stimulation at 50 Hz with 0.9 V,
      and stimulation at 2 Hz at 2 V did not result in any motor stimulation. RFA was
      then carried out at 70 degrees C for 80 seconds, followed by injection of 20 mg
      of methylprednisolone. The patient's Numeric Rating Scale pain score decreased
      from 9/10 to 3/10 after the RFA. She had about 70% relief for about 6 months.
      DISCUSSION:   There is evidence that intercoccygeal disks can be a source of
      coccydynia. Immunohistochemistry has shown mechanoreceptors in intercoccygeal
      disks, and coccygeal discography has been shown to reproduce coccygeal pain.
      Intercoccygeal disk injection is described as a therapeutic option in the
      literature. Because various RFA techniques have been successfully used for
      intervertebral diskogenic pain, the decision was made to attempt RFA at the 1st
      intercoccygeal disk with resultant significant long-term improvement.

PMID- 21087411
TI  - An open-label comparison of nabilone and gabapentin as adjuvant therapy or
      monotherapy in the management of neuropathic pain in patients with peripheral
      neuropathy.
AB  - Neuropathic pain (NeP) is prevalent in patients with peripheral neuropathy (PN),
      regardless of etiology. We sought to compare the efficacy of the cannabinoid
      nabilone as either monotherapy or adjuvant therapy with a first-line medication
      for NeP, gabapentin, in a patient population with PN-NeP. Patients diagnosed with
      PN-NeP were permitted to initiate monotherapy (nabilone or gabapentin) or add one
      of these two medications (adjuvant therapy) to their existing NeP treatment
      regimen in a non-randomized open-label nature. Baseline data collected included a
      primary outcome (visual analog scores [VAS] of pain) and secondary outcomes
      (quality of life [EuroQol 5 Domains and Short-Form 36] assessments and
      assessments of sleep [Medical Outcomes Sleep Study Scale {MOSSS}], anxiety and
      depression [Hospital Anxiety and Depression Scale], and pain [Brief Pain
      Inventory]). Reassessment and modulation of dosing and/or medications occurred at
      3- and 6-month intervals. Medication adverse effects and drug efficacy, as well
      as questionnaires, were assessed at 6 months. Matched analysis of variance
      testing was performed to compare 3- and 6-month scores with baseline, as well as
      to compare therapies at equal time points. Significant improvements in pain VAS
      were seen in all treatment groups at 6 months. Numerous sleep parameters within
      MOSSS, Brief Pain Inventory, and Short-Form 36 improved in patients receiving
      nabilone or gabapentin either as monotherapy or adjuvant treatment. Hospital
      Anxiety and Depression Scale-A scores were significantly improved in all
      treatment groups. Sleep adequacy and the sleep problems index within the MOSSS
      improved in nabilone monotherapy patients in particular. The benefits of
      monotherapy or adjuvant therapy with nabilone appear comparable to gabapentin for
      management of NeP. We advocate for head-to-head randomized, double-blind studies
      for current therapies for NeP in order to determine potential advantages
      beneficial in this patient population.

PMID- 21087412
TI  - The noninferiority trial: don't don't do it.

PMID- 21087413
TI  - First case of Toxocara eosinophilic ascites after combined pancreas and kidney
      transplantation.

PMID- 21087414
TI  - Height contributes to the gender difference in wait-list mortality under the MELD
      based liver allocation system.
AB  - This study examined factors associated with the gender disparity in wait-list
      mortality in the MELD era. Adult patients listed for liver transplantation from
      2002 to 2008 were included. Females [12 585(36%)] and males [22 126(64%)]
      differed clinically by age (54 vs. 52 years), height (1.6 vs. 1.8 m), listing
      estimated glomerular filtration rate [(eGFR); 70 vs. 83 mL/min] and cirrhosis
      etiology. Holding MELD constant, females were at 19% (95% CI, 1.13-1.25, p <
      0.001) higher risk of wait-list mortality than males under the current allocation
      system. The relative hazard increased with worsening renal function, whether
      measured by serum creatinine or eGFR. Adjustment for MELD, age, African-American
      race, cirrhosis etiology, region and ABO group attenuated this relative hazard
      (HR 1.16; 95% CI, 1.10-1.22; p < 0.001) but additional adjustment for height
      completely explained this gender disparity in wait-list mortality (HR 1.05; 95%
      CI, 0.98-1.12; p = 0.2). Transplantation rates, however, remained lower among
      females, even after adjustment for height (HR 0.88; 95% CI, 0.82-0.92; p <
      0.001). In conclusion, under the current liver allocation system, women have a
      19% increased risk of wait-list mortality compared to men with the same MELD
      scores. Height contributes to this gender disparity, possibly reflecting
      differences in transplantation rates for shorter individuals.

PMID- 21087415
TI  - Usefulness of exhaled nitric oxide to guide risk stratification for bronchiolitis
      obliterans syndrome after lung transplantation.
AB  - The aim of this study was to assess fractional exhaled nitric oxide (FeNO) for
      the early diagnosis of bronchiolitis obliterans syndrome (BOS) after lung
      transplantation (LTX). 611 FeNO measurements in 166 consecutive patients were
      classified depending on BOS stage at the time of assessment and course during
      minimum follow-up of 3 months: (1) stable non-BOS, (2) unstable non-BOS, (3)
      stable BOS and (4) unstable BOS. Unstable course was defined as new onset of
      BOS>=1 or progression of BOS. FeNO before unstable course was significantly
      increased in comparison to their stable counterparts (non-BOS: 28.9 +/- 1.2 ppb,
      n = 40 vs. 16.4 +/- 0.8 ppb, n = 131 and BOS: 32.5 +/- 1.3 ppb, n = 35 vs. 15.3
      +/- 0.8 ppb, n = 26; p = 0.01 each). Average time from FeNO reading to onset of
      deterioration was 117 +/- 9 days in non-BOS and 136 +/- 9 days in BOS patients.
      The positive and negative predictive value of FeNO >20 ppb for BOS was 69.0% and
      96.9%, respectively. Serial measurements demonstrated significantly lower mean
      individual variation in stable recipients as compared to stable patients
      switching to unstable course (3.2 +/- 0.3 ppb vs. 12.7 +/- 1.4 ppb, p = 0.02). In
      particular, the excellent negative predictive value of persistently low FeNO
      readings for future BOS make FeNO assessments a useful tool for continuous risk
      stratification after LTX.

PMID- 21087416
TI  - Coccidioidomycosis in liver transplant recipients in an endemic area.
AB  - Coccidioidomycosis is an infection caused by Coccidioides species, which are
      endemic for the Southwestern United States and parts of Central America and South
      America. Most infected individuals are asymptomatic or have mild-to-moderate
      respiratory illness. Coccidioidomycosis is more severe in patients with depressed
      cellular immunity, such as organ transplant recipients. We retrospectively
      reviewed charts of 391 liver transplant recipients (mean follow-up, 38.7 months;
      range, 2-105 months). Before transplantation, 12 patients had a history of
      coccidioidomycosis and 13 patients had asymptomatic seropositivity. Of these 25
      patients, 23 had no active coccidioidomycosis posttransplantation and 2 had
      reactivated infection. One of 5 patients with indeterminate serology before
      transplantation died of disseminated coccidioidomycosis shortly after
      transplantation. De novo coccidioidomycosis developed in 12 patients (3%) who had
      no evidence of coccidioidomycosis pretransplantation. Of 15 total episodes of
      posttransplantation coccidioidomycosis, 10 (66%) occurred during the first year.
      Dissemination was noted in 33% of active coccidioidomycosis after
      transplantation; two patients (13%) died of coccidioidomycosis. Because most
      coccidioidal infections occurred in the first posttransplantation year despite
      targeted antifungal prophylaxis, we recommend a new strategy of universal
      antifungal prophylaxis for 6-12 months for liver transplant recipients who reside
      in the endemic area.

PMID- 21087417
TI  - Body mass index, waist circumference and mortality in kidney transplant
      recipients.
AB  - Higher body mass index (BMI) appears paradoxically associated with better
      outcomes in patients with chronic kidney disease. Whereas higher BMI reflects
      both increased visceral and subcutaneous fat and/or muscle mass, a combined
      assessment of BMI and waist circumference may enable differentiation of visceral
      adiposity from muscle and/or nonvisceral fat mass. We examined the association of
      BMI and waist circumference with all-cause mortality in a prospective cohort of
      993 kidney transplant recipients. Associations were examined in Cox models with
      adjustment for demographic and comorbid conditions and for inflammatory markers.
      Unadjusted death hazard ratios (95%CI) associated with one standard deviation
      higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20
      (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower
      mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p <
      0.001), and higher waist circumference was more strongly associated with higher
      mortality after adjustment for BMI (2.18 [1.55-3.08], p < 0.001). The
      associations of waist circumference with mortality remained significant after
      additional multivariable adjustments. Higher BMI and waist circumference display
      opposite associations with mortality in kidney transplant recipients. Waist
      circumference appears to be a better prognostic marker for obesity than BMI.

PMID- 21087418
TI  - Late cerebral ischaemia after subarachnoid haemorrhage: is cerebrovascular
      receptor upregulation the mechanism behind?
AB  - Late cerebral ischaemia after subarachnoid haemorrhage (SAH) carries high
      morbidity and mortality because of reduced cerebral blood flow (CBF) and
      subsequent cerebral ischaemia. This is associated with upregulation of
      contractile receptors in cerebral artery smooth muscles via the activation of
      intracellular signalling. In addition, delayed cerebral ischaemia after SAH is
      associated with inflammation and disruption of the blood-brain barrier (BBB).
      This article reviews recent evidence concerning the roles of vasoconstrictor
      receptor upregulation, inflammation and BBB breakdown in delayed cerebral
      ischaemia after SAH. In addition, recent studies investigating the role of
      various intracellular signalling pathways in these processes and the
      possibilities of targeting signalling components in SAH treatment are discussed.
      Studies using a rat SAH model have demonstrated that cerebral arteries increase
      their sensitivity to endogenous agonists such as ET-1 and 5-HT by increasing
      their smooth muscle expression of receptors for these after SAH. This is
      associated with reduced CBF and neurological deficits. A number of signal
      transduction components mediating this receptor upregulation have been
      identified, including the MEK-ERK1/2 pathway. Inhibition of MEK-ERK1/2 signalling
      has been shown to prevent cerebrovascular receptor upregulation and normalize CBF
      and neurological function after SAH in rats. At the same time, in rat SAH,
      certain cytokines and BBB-regulating proteins are upregulated in cerebral artery
      smooth muscles and treatment with MEK-ERK1/2 inhibitors prevents the induction of
      these proteins. Thus, inhibitors of MEK-ERK1/2 signalling exert multimodal
      beneficial effects in SAH.

PMID- 21087419
TI  - Core body temperature and the thermoneutral zone: a longitudinal study of normal
      human pregnancy.
AB  - AIM: Using a longitudinal study design, we investigated changes in maternal core
      temperature and ambient temperatures before and after a localized cooling
      procedure to the right hand. METHODS: Fifteen pregnant women participated. The
      experiments were sequentially performed for 21 month periods on each subject:
      from the 8th week of gestation to 1 year after delivery on seven separate
      occasions (gestational weeks 8, 16, 26, 36 and 12, 24, 52 weeks post-partum). The
      experiments were conducted in a climactic chamber, allowing ambient temperature
      adjustment to each subjects' thermoneutral zone determined using Doppler
      ultrasound of the digital artery. RESULTS: Maternal core temperature decreased
      from 37.1  degrees C (week 8) towards term, reaching a nadir (36.4  degrees C) at
      12 weeks post-partum (P < 0.001). The ambient temperature required to reach the
      thermoneutral zone changed significantly from 26.5  degrees C (week 8) falling to
      its lowest point: 23.0  degrees C (week 36) (P < 0.001), then stabilized from 24
      weeks post-partum. CONCLUSION: Maternal core temperature is highest in the first
      trimester but falls during pregnancy to a nadir 3 months post-partum. The ambient
      temperature required to reach the thermoneutral zone was 4  degrees C lower at 36
      weeks of gestation compared with early pregnancy and late post-partum. Human
      temperature regulation is altered in pregnancy and for at least 3 months post
      partum.

PMID- 21087420
TI  - Integrins: versatile receptors controlling melanocyte adhesion, migration and
      proliferation.
AB  - From the onset of melanocyte specification from the neural crest, throughout
      their migration during embryogenesis and until they reside in their niche in the
      basal keratinocyte layer, melanocytes interact in dynamic ways with the
      extracellular environment of the growing embryo. To recognize and to adhere to
      their environment, melanocytes depend on heterodimeric cell surface receptors of
      the family of integrins. In addition to the control of adhesive interactions
      between melanocytes and the extracellular matrix scaffold secreted by fibroblasts
      and keratinocytes, the integrin receptors allow cells also to sense the
      mechanical condition of the extracellular environment, responding by
      intracellular signaling, triggering cell survival, proliferation or migration
      events. In this review, we summarize the recently emerged concepts that explain
      integrin-dependent adhesion and how this adhesion system interfaces with integrin
      dependent signaling events. The gained information will help to understand
      melanocyte behavior in pathological situations such as melanoma growth and
      metastasis formation.

PMID- 21087421
TI  - Congenital heart disease--a great year.

PMID- 21087422
TI  - Left ventricular non compaction in children.
AB  - Left ventricular non compaction (LVNC) is a myocardial disease characterized by a
      hypertrabeculated myocardium. The hypertrabeculations in the left ventricular
      wall define deep recesses communicating with the left ventricular chamber where
      blood penetrates with increased risk of blood clots in the meshwork of the
      prominent trabeculations. The left ventricular apex and the free wall are
      particularly affected. During in utero ventriculogenesis, myocardial blood supply
      is initially linked to the presence of sinusoids, in which blood penetrates and
      diffuses nutriments and oxygen to myocardial cells. Progressively, with the
      development of the heart and the increase of cells demand of blood, coronary
      arteries system develops. This step is associated with myocardial modification
      that leads to compaction of hypertrabeculated myocardial net. Probably, the
      premature interruption of this process leads to ventricular noncompaction. Many
      studies have been conducted in adults with hypertrabeculated myocardium. To date,
      data regarding childhood LVNC are sparse. The aim of this review is to summarize
      the clinical and preclinical knowledge about LVNC in children.

PMID- 21087423
TI  - The fetal ductus arteriosus and its abnormalities--a review.
AB  - The ductus arteriosus (DA) is a small vessel with major functional importance for
      the integrity of the fetal circulation. Technical advances in prenatal
      diagnostics facilitate appropriate echocardiographic estimation of the ductal
      flow and its abnormalities. Despite the emerging knowledge of its embryological
      background and developmental processes during advancing gestation we still have
      to face unresolved questions regarding the identification and optimal
      surveillance of fetuses at risk of premature closure of the ductus. Prenatal
      administration of tocolytics such as indomethacin should be monitored by close
      Doppler sonographic scans to follow the ductal circulation. Understanding the
      transcriptional regulation of normal DA development, maturation, and closure of
      the arterial duct as well as the hemodynamic changes during pregnancy and after
      delivery may provide additional targets for rational drug design to either close
      or open the DA, both antenatally and postnatally.

PMID- 21087424
TI  - Echocardiographic parameters that predict outcome in aortic atresia patients
      undergoing comprehensive stage II procedure.
AB  - BACKGROUND: The hybrid procedure is one option for palliating patients with
      hypoplastic left heart syndrome. As experience increases with this palliation,
      the physiology and its influence on outcome can be better assessed. The goal of
      this study was to determine if echocardiographic parameters correlate with post
      operative variables in patients with aortic atresia undergoing the comprehensive
      Stage II procedure. METHODS: Retrospective chart review on all patients with
      aortic atresia, who underwent the comprehensive Stage II procedure from January
      2002 to December 2008, was performed. Echocardiographic indices were evaluated
      and correlations were made with peri-operative and hospital variables. Pair-wise
      Pearson's correlation tests were used to analyze the associations between
      continuous measures. RESULTS: Thirty-four patients met inclusion criteria. Age at
      comprehensive Stage II procedure was 0.45 +/- 0.13 years and body surface area
      was 0.31 +/- 0.04 m(2). Right ventricle (RV) percentage change was 45 +/- 10%,
      eccentricity index was 1.96 +/- 0.45, estimated systemic cardiac output was 7.68
      +/- 2.56 L/min/m(2) and estimated effective systemic cardiac output was 5.15 +/-
      2.24 L/min/m(2). Retrograde patent ductus arteriosu (PDA) velocity time integral
      (VTI) correlated with log pre-bypass lactate and maximum lactate (r = 0.53,
      0.44). PDA regurgitant fraction correlated with log post-bypass lactate, length
      of intubation, and urine output on day four (r = 0.39, 0.46, -0.37). RV
      percentage change correlated with log pre-bypass lactate, and urine output on
      days four and five (r =-0.38, 0.43, 0.54). No echocardiographic parameter
      predicted renal or liver insufficiency, dialysis, extracorporeal membrane
      oxygenation use, or hospital death. CONCLUSION: Retrograde PDA VTI and RV percent
      change correlated with some peri-operative variables though no echocardiographic
      parameter was associated with any major morbidities or mortality. Newer
      echocardiographic techniques may better predict comprehensive stage II outcomes.

PMID- 21087425
TI  - Hemodynamics and cerebral oxygenation following repair of tetralogy of Fallot:
      the effects of converting from positive pressure ventilation to spontaneous
      breathing.
AB  - PURPOSE: Following corrective surgery for tetralogy of Fallot (TOF),
      approximately one-third of these patients develop low cardiac output (CO) due to
      right ventricular (RV) diastolic heart failure. Extubation is beneficial in these
      patients because the fall in intrathoracic pressure that occurs with conversion
      from positive pressure breathing to spontaneous breathing improves venous return,
      RV filling and CO. We hypothesized that if CO were to increase but remain limited
      following extubation, the obligatory increase in perfusion to the respiratory
      pump that occurs with loading of the respiratory musculature may occur at the
      expense of other vital organs, including the brain. MATERIALS AND METHODS: We
      conducted a retrospective analysis of all patients undergoing repair of TOF and
      monitoring of cerebral oxygenation using near infrared spectroscopy. We evaluated
      the following parameters two hours prior to and following extubation: mean and
      systolic arterial blood pressure (MBP, SBP), right atrial pressure (RAP), heart
      rate (HR) and cerebral oxygenation. RESULTS: The study included 22 patients. With
      extubation, MBP and SBP increased significantly from 67.3 +/- 6.5 to 71.1 +/- 8.4
      mm Hg (P= 0.004) and from 87.2 +/- 8.6 to 95.9 +/- 10.9 mm Hg (P= 0.001),
      respectively, while the HR remained unchanged (145 vs. 146 bpm). The RAP remained
      unchanged following extubation (11.9 vs. 12.0 mm Hg). Following extubation,
      cerebral oxygen saturations increased significantly from 68.5 +/- 8.4 to 74.2 +/-
      7.9% (P < 0.0001). Cerebral oxygen saturations increased by >=5% in 11 of 22
      patients and by >=10% in 5 of 22 patients. CONCLUSION: We conclude that
      converting from positive pressure ventilation to spontaneous negative pressure
      breathing following repair of TOF significantly improves arterial blood pressure
      and cerebral oxygenation.

PMID- 21087426
TI  - Adrenal insufficiency in hemodynamically unstable neonates after open-heart
      surgery.
AB  - OBJECTIVE: To investigate if the low dose (1 ug) ACTH stimulation test
      appropriately assesses adrenal responsiveness in neonates undergoing open-heart
      surgery requiring cardio-pulmonary bypass. DESIGN: In this retrospective study,
      adrenal axis response was assessed on the first post-operative day with the low
      dose (1 ug) ACTH stimulation test. Age, gender, weight, RACHS category, inotrope
      score, and baseline and post-stimulation cortisol levels were collected. The
      association between basal serum cortisol levels and degree of response to the
      ACTH stimulation test was also investigated. SETTING: Tertiary care referral
      center. PATIENTS: Twenty-one neonates who underwent neonatal cardiac surgery on
      cardiopulmonary bypass and underwent an ACTH stimulation test. Interventions. 
      Hydrocortisone 50 mg/m(2) bolus in four divided doses daily. OUTCOME MEASURES:
      Response to the low dose (1 ug) ACTH stimulation was assessed. RESULTS: All
      neonates with hemodynamic instability in the immediate post-operative period had
      low basal serum cortisol levels. The basal mean serum cortisol level for the 21
      patients who underwent the low dose ACTH stimulation test was 7.3 ug/dL (median
      2.2, range 0.7-42). The mean serum cortisol level increased after the ACTH
      stimulation test in the 21 patients to 39.6 ug/dL (median 38, range 79-17). The
      mean inotrope score in the first 24 hours after surgery was 24 (median 17.5,
      range 7-76.5) and decreased to 17 (median 14, range 5-52.3) 24-48 hours after
      surgery. At 48 hours post-surgery the mean arterial pressure in the groups with a
      serum cortisol increase after ACTH stimulation (<30 ug/dL vs. >50 ug/dL) was
      significantly different (P value 0.026). CONCLUSIONS: The low dose (1 ug) ACTH
      stimulation test is a valid test to assess adrenal responsiveness among neonates
      after open heart surgery requiring CPB. Traditionally used basal serum cortisol
      level cutoff of <20 ug/dL used to define relative adrenal insufficiency may not
      be applicable in neonates undergoing open heart surgery on CPB thus indicating
      the need for re-defining adrenal insufficiency in this patient population.

PMID- 21087427
TI  - Arrhythmia recurrence in adult patients with single ventricle physiology
      following surgical Fontan conversion.
AB  - OBJECTIVES: To evaluate the incidence of atrial tachy-arrhythmia (AT) recurrence
      following conversion from right atrial-pulmonary artery (RA-PA) Fontan to total
      cavopulmonary connection (TCPC) in adults. BACKGROUND: AT is a recognized sequel
      of Fontan palliation, especially in RA-PA Fontans, and is associated with
      significant morbidity. While catheter ablation achieves fairly reliable short
      term success with low morbidity, conversion to TCPC with arrhythmia surgery is a
      highly effective treatment option for the classical Fontan patients with
      incessant AT. METHODS: Single center retrospective review. RESULTS: Twenty-seven
      adults underwent Fontan conversion from RA-PA to TCPC, mostly for AT indications
      (n = 24). Nine (33%) underwent conversion to a lateral tunnel (LT) and 18 (67%)
      to an extracardiac (EC) Fontan. Two patients died <30 days post-operatively. Both
      had liver failure and had been turned down for cardiac/liver transplantation. In
      hospital complications occurred in 15/27 patients (55%), including recurrence of
      AT requiring cardioversion in six patients (22%) and persistent pleural effusions
      in 4 (15%). Mean follow-up was 4.2 years (range 3 months-14 years). Functional
      capacity improved from mean New York Heart Association (NYHA) class 1.8 pre
      conversion to 1.2 post-conversion (P= 0.008). Twenty-one patients had concomitant
      arrhythmia surgery (MAZE in 12 patients with IART and Cox-MAZE in nine patients
      with A-Fib +/- IART). Of these, 3/21 (14%) had AT recurrence >3 months following
      conversion. CONCLUSIONS: Conversion from RA-PA Fontan to TCPC, with arrhythmia
      surgery, decreases AT recurrence and improves functional capacity. The risk of
      peri-operative mortality is highest in patients with cirrhosis. AT recurred in
      14% of patients.

PMID- 21087428
TI  - Sepsis in premature newborns with congenital heart disease.
AB  - OBJECTIVE: To determine the incidence and distribution of neonatal sepsis in
      premature newborns with congenital heart disease (CHD) according to gestational
      and postnatal age, time of onset, and type and frequency of causing agents, and
      compare it with premature newborns without CHD. DESIGN, SETTING, PATIENTS: A
      clinical investigation on 80 premature newborns admitted to neonatal intensive
      care unit (NICU) of Pediatric Clinic University Medical Center Sarajevo, Bosnia
      and Herzegovina, between October 23, 2007 and March 18, 2009. We analyzed the
      incidence and distribution of neonatal sepsis in premature newborns with CHD
      according to gestational and postnatal age, time of onset, and type and frequency
      of causing agents, and compared it with premature NICU patients without CHD.
      RESULTS: Of the 80 premature newborns included in our study, 14 had CHD with
      patent ductus arteriosus as the most common type of anomaly. Culture-proven
      sepsis was diagnosed in 28.57% premature newborns with CHD and 12.12% premature
      newborns without CHD. The three most common causing agents were Staphylococcus
      aureus, Klebsiella species, and Serratia species. CONCLUSION: Premature newborns
      with CHD have a higher risk of acquiring sepsis during hospitalization in NICU,
      probably because of longer duration of hospitalization and need for invasive
      procedures such as mechanical ventilation, central venous catheters, and
      parenteral nutrition.

PMID- 21087429
TI  - Device closure of patent ductus arteriosus in Marfan patients: safety and effect
      on the aortic root diameter.
AB  - OBJECTIVES: There is little evidence in the medical literature about safety of
      PDA device closure and its effects on aortic root diameter in Marfan patients. We
      reported on nine Marfan patients whose ducts were occluded by coil or Amplatzer
      Duct Occluder. PATIENTS AND INTERVENTIONS: Two patients had aneurismal type E
      ducts which were closed by a single coil, respectively. The others had conical
      ducts for which even Amplatzer occluder, stiff, or double coils were used.
      RESULTS: No untoward consequence was found during a median follow up period of
      18.5 months (range 3 months to 6.33 years). Two patients had small residual
      shunts. The observed change in the mean ratio of aortic root diameter to its
      estimated value was statistically insignificant in seven patients who had
      complete data on their aortic root diameter before PDA closure and during the
      follow up. CONCLUSIONS: We concluded that PDA device closure in Marfan patients
      is safe. Risk of residual shunt is higher even after closure of small ducts.

PMID- 21087430
TI  - Short-term outcome of infants presenting to pediatric intensive care unit with
      new cardiac diagnoses.
AB  - AIMS: To outline the etiology, clinical course, short-term survival to discharge
      and neurological outcome of infants (<1 yr) with new cardiac diagnoses presenting
      to a pediatric intensive care (PICU) unit with acute cardiac compromise. METHODS:
      Retrospective search of a computerized database and medical case notes for all
      acute cardiac admissions to PICU from June 2001 to 2006. Pre-existing hospital
      based patients with new cardiac diagnoses were excluded. RESULTS: Seventy
      patients were identified, 38 (54%) of whom were male. There were six main
      subgroups: obstructive left heart lesions (n= 20), transposition of the great
      arteries (TGA) (n= 9), total anomalous pulmonary venous drainage (TAPVD) (n= 7),
      dilated cardiomyopathy (n= 11), arrhythmia (n= 12), and others (n= 11). Fifty
      nine patients (84%) were external referrals to our center. The median age at
      presentation was 13.5 days (0-272) with median duration of symptoms of 1 day (0
      21). The median base deficit at presentation was -7.6 mEq/L (-43 to +4.2). Fifty
      three patients (76%) required respiratory support with a median duration of
      ventilation of 4 days (1-49). Fifty-six patients (80%) required inotropic
      support. The median PICU stay was 7 days (1-64) with a median total hospital stay
      of 16 days (1-71). Six patients (9%) died prior to discharge. Of the survivors 7
      (11%) had seizure activity or evolving clinical neurological abnormalities.
      CONCLUSIONS: Cardiovascular compromise due to previously unrecognized congenital
      or acquired heart disease is associated with clinically significant morbidity and
      mortality. Longer term follow-up is required to evaluate the initial effect of
      poor cardiac output and hypoxia on long-term neurodevelopmental outcome.

PMID- 21087432
TI  - Pentalogy of Cantrell with left ventricular diverticulum: a case report and
      review of literature.
AB  - Pentalogy of Cantrell is a rare congenital anomaly involving deficiency of the
      following structures: anterior diaphragm, supraumbilical abdominal wall,
      diaphragmatic pericardium, lower sternum, and associated congenital intracardiac
      abnormality. We describe a 3-month-old child with this syndrome having left
      ventricular diverticulum along with omphalocele who presented to us with a
      pulsating mass in the epigastrium. The defect was evaluated and defined by
      computed tomography scan. A team of pediatric, cardiac, and plastic surgeons
      successfully repaired the defects. This case report discusses the review of
      literature along with management options and concludes that there must be an
      emphasis on early repair of left ventricular diverticulum to prevent
      complications. Antenatal ultrasound can also detect the anomaly, and early
      postnatal diagnosis of the syndrome, followed by immediate surgical repair, can
      prevent lethal complications.

PMID- 21087431
TI  - Craniorachischisis and heterotaxia with heart disease in twins: link or change
      nature?
AB  - Craniorachischisis is a rare neural tube defect in which both acrania and a
      complete schisis of the vertebral column are present. Heterotaxy results from
      failure to establish normal left-right asymmetry during embryonic development and
      is characterized by a variable group of congenital anomalies that include complex
      cardiac malformations and situs inversus or situs ambiguous. We report a
      diamniotic twin pregnancy with two malformed fetuses affected one by
      craniorachischisis and the other by heterotaxya with paired right-sided viscera,
      asplenia, and complex congenital heart disease. The occurrence of severe
      congenital anomalies in both members of the twin pair implies a strong influence
      of genetic factors. At present, the genetic basis determining the different
      phenotypes observed in our twins is unknown. Our case with the simultaneous
      presence of both midline and laterality defects in twins supports the hypothesis
      that the midline plays a critical role in establishing left-right asymmetry in
      the body and that a mutation in a gene responsible for both heterotaxy and
      midline defects may be strongly supposed.

PMID- 21087433
TI  - Rate dependent QS pattern in an acute Kawasaki disease.
AB  - Kawasaki disease (KD) is associated with pancarditis and complicated by coronary
      artery (CA) inflammation. In the present case, we were confronted with a very ill
      KD patient with first degree atrioventricular block and QS pattern on the
      electrocardiogram. This unusual pattern was transient and intermittent. It
      reflected a conduction disturbance in the context of an acute myocarditis rather
      than an immediate CA complication. We herein discuss the differential diagnoses
      of a rarely observed electrocardiographic finding in the young.

PMID- 21087434
TI  - Anomalous origin of the left coronary artery from the pulmonary artery in
      Alagille syndrome.
AB  - Alagille syndrome is a dominantly inherited multisystem disorder involving
      multiple organs including the liver, heart, eyes, face, and skeleton. Congenital
      heart defects, the majority of which are right-sided, contribute significantly to
      the mortality of these patients. We report a patient with Alagille syndrome who
      presented with mitral valve regurgitation requiring valvuloplasty and subsequent
      mitral valve replacement. The patient was ultimately diagnosed with anomalous
      origin of the left coronary artery from the pulmonary artery and underwent
      successful reimplantation.

PMID- 21087435
TI  - Catheter ablation of primary supraventricular tachycardia substrate presenting as
      atrial fibrillation in adolescents.
AB  - BACKGROUND: Atrial fibrillation is rarely encountered in children and
      adolescents, and these cases are usually secondary to myocardial diseases,
      electrical abnormalities, or scar related in postoperative congenital heart
      disease patients. Untreated sustained atrial fibrillation may lead to tachycardia
      induced cardiomyopathy and/or systemic thromboembolization. OBJECTIVE: The
      objective here is to describe our findings in four adolescent patients presenting
      with recurrent atrial fibrillation. DESIGN: We report here the results of the
      findings in four patients who presented with recurrent clinical atrial
      fibrillation. RESULTS: Each of the four underwent electrophysiologic study that
      revealed a primary reentry or automatic supraventricular tachycardia (SVT)
      substrate, which was able to be treated with radiofrequency ablation. In three of
      the four cases, elimination of the primary substrate prevented subsequent
      recurrence of SVT symptoms or documented SVT and/or atrial fibrillation.
      CONCLUSION: Children and adolescents presenting with atrial fibrillation warrant
      an exhaustive search for a treatable primary cause of myocardial or electrical
      disease. If present, a primary SVT substrate may be successfully ablated to
      prevent recurrence of atrial fibrillation and any associated complications.
      Pulmonary vein isolation is rarely indicated in adolescents and should be
      avoided.

PMID- 21087436
TI  - Successful correction of a total anomalous venous connection in a 63-year-old
      male--case report and review of the literature.
AB  - Total anomalous pulmonary venous connection is a rare variant of cyanotic
      congenital heart disease and usually requires surgical correction within the
      first few months of life. We report midterm results of a 63-year-old male with
      intracardiac total anomalous venous return into the coronary sinus who presented
      with congestive predominantly right heart failure and underwent corrective
      surgery with unroofing of the coronary sinus and patch closure of the secundum
      atrial septal defect.

PMID- 21087437
TI  - Successful pregnancies in two women with hypoplastic left heart syndrome.
AB  - OBJECTIVE: Hypoplastic left heart syndrome (HLHS) is a relatively common complex
      congenital heart defect. Prior to development of staged reconstruction (i.e.,
      Norwood procedure), HLHS was almost universally fatal within months of birth.
      Early survivors of the Norwood procedure are now reaching reproductive age. We
      report successful pregnancies in two such women. PATIENTS: The first patient was
      a 20-year-old woman transferred from a community hospital at 33 3/7 weeks
      gestation because of preterm labor, suspected preeclampsia, and mild chronic
      hypoxemia. She had normal systemic ventricular shortening without significant
      valvar regurgitation but severe neoaortic dilatation. A fetal ultrasound
      demonstrated intrauterine growth restriction. An urgent Cesarean section was
      performed at 33 6/7 weeks gestation, given breech position and intractable
      preterm labor. The second patient, a 23-year-old woman followed at this
      institution through pregnancy, presented with preterm labor at 36 weeks
      gestation. Her systemic ventricular shortening was normal, with mild tricuspid
      regurgitation but without neoaortic dilation or regurgitation. She developed
      active labor at 36 3/6 weeks, and had a spontaneous vaginal delivery of a small
      for gestational age infant. Both women tolerated labor and childbirth without
      complication. Neither infant had evidence of structural heart disease on fetal
      echocardiography or physical examination. CONCLUSIONS: These cases, the first
      reported successful pregnancies in mothers with HLHS, highlight the challenges of
      pregnancy among women with complex congenital heart disease in general and raise
      several considerations specific to HLHS.

PMID- 21087438
TI  - Fetal goiter mimicking anomalous pulmonary venous connection.
AB  - Fetal thyroid dysfunction is a well-recognized cause of secondary cardiac
      disease, including arrhythmias and hydrops fetalis, but has not previously been
      reported to mimic structural heart disease. We describe a case of fetal goiter
      presenting as suspected anomalous pulmonary venous connection and highlight
      lessons for the obstetrician and pediatric cardiologist with regard to imaging as
      well as communication.

PMID- 21087439
TI  - A newborn with congenital complete atrioventricular block, lissencephaly, and
      skeletal abnormalities: a case of suspected cytomegalovirus infection.
AB  - We present a case of congenital complete atrioventricular block in a preterm
      microcephalic male with multiple additional congenital anomalies, including
      spinal and rib abnormalities. The heart was structurally normal, and maternal
      tests for autoimmune disorders were negative. The brain had an immature
      lissencephalic appearance, suggestive of an insult early in gestation. Genetic
      testing was normal, virtually excluding chromosomal disorders that are known to
      cause lissencephaly. Viral studies were suggestive of cytomegalovirus infection
      during early gestation, and we believe that the patient's clinical presentation
      was most likely the result of an early cytomegalovirus infection. The finding of
      complete atrioventricular block in a patient with presumed cytomegalovirus
      infection would represent a very rare complication. "Isolated" complete
      atrioventricular block in a fetus should be considered an incentive for an
      extensive work-up in search for a possible etiology, rather than accepted as a
      final diagnosis.

PMID- 21087442
TI  - Pharmacological recruitment of the GABAergic tail of the ventral tegmental area
      by acute drug exposure.
AB  - BACKGROUND AND PURPOSE: The tail of the ventral tegmental area (tVTA), also
      called the rostromedial tegmental nucleus, is a newly defined brain structure and
      a potential control centre for dopaminergic activity. It was identified by the
      induction of DeltaFosB following chronic cocaine exposure. In this work, we
      screened 20 drugs for their ability to induce FosB/DeltaFosB in the tVTA.
      EXPERIMENTAL APPROACH: Immunohistochemistry following systemic drug
      administration was used to study FosB/DeltaFosB induction in the tVTA of adult
      rats. Double-staining was used to determine whether dopamine or GABA neurones are
      involved in this induction. KEY RESULTS: The acute injection of the
      psychostimulant drugs cocaine, D-amphetamine, (+/-)-3,4
      methylenedioxymethamphetamine (MDMA), methylphenidate or caffeine, induced the
      expression of FosB/DeltaFosB in the tVTA GABAergic cells. No induction was
      observed following exposure to ethanol, diazepam, gamma-hydroxybutyric acid
      (GHB), morphine, ketamine, phencyclidine (PCP), Delta(9)-tetrahydrocannabinol
      (THC), sodium valproic acid or gabapentin. To evaluate the role of monoamine
      transporters in the psychostimulant-induced expression of FosB/DeltaFosB, we
      tested the antidepressant drugs reboxetine, nortriptyline, fluoxetine and
      venlafaxine (which target the noradrenaline and/or the 5-hydroxytryptamine
      transporters), the 5-hydroxytryptamine releasing agent dexfenfluramine, and the
      dopamine transporter inhibitor GBR12909. Only GBR12909 was able to induce
      FosB/DeltaFosB expression in the tVTA, showing that this induction is mediated by
      dopamine. CONCLUSIONS AND IMPLICATIONS: Newly described brain structures may help
      to increase our knowledge of brain function, pathology and targets for
      treatments. FosB/DeltaFosB induction in the tVTA is a common feature of drugs
      sharing psychostimulant properties but not of drugs sharing risk of abuse.

PMID- 21087444
TI  - Oral administration of Parabacteroides distasonis antigens attenuates
      experimental murine colitis through modulation of immunity and microbiota
      composition.
AB  - Commensal bacteria have been shown to modulate the host mucosal immune system.
      Here, we report that oral treatment of BALB/c mice with components from the
      commensal, Parabacteroides distasonis, significantly reduces the severity of
      intestinal inflammation in murine models of acute and chronic colitis induced by
      dextran sulphate sodium (DSS). The membranous fraction of P. distasonis (mPd)
      prevented DSS-induced increases in several proinflammatory cytokines, increased
      mPd-specific serum antibodies and stabilized the intestinal microbial ecology.
      The anti-colitic effect of oral mPd was not observed in severe combined
      immunodeficient mice and probably involved induction of specific antibody
      responses and stabilization of the intestinal microbiota. Our results suggest
      that specific bacterial components derived from the commensal bacterium, P.
      distasonis, may be useful in the development of new therapeutic strategies for
      chronic inflammatory disorders such as inflammatory bowel disease.

PMID- 21087443
TI  - Prolonged recurrence-free survival following OK432-stimulated dendritic cell
      transfer into hepatocellular carcinoma during transarterial embolization.
AB  - Despite curative locoregional treatments for hepatocellular carcinoma (HCC),
      tumour recurrence rates remain high. The current study was designed to assess the
      safety and bioactivity of infusion of dendritic cells (DCs) stimulated with
      OK432, a streptococcus-derived anti-cancer immunotherapeutic agent, into tumour
      tissues following transcatheter hepatic arterial embolization (TAE) treatment in
      patients with HCC. DCs were derived from peripheral blood monocytes of patients
      with hepatitis C virus-related cirrhosis and HCC in the presence of interleukin
      (IL)-4 and granulocyte-macrophage colony-stimulating factor and stimulated with
      0.1 KE/ml OK432 for 2 days. Thirteen patients were administered with 5 * 106 of
      DCs through arterial catheter during the procedures of TAE treatment on day 7.
      The immunomodulatory effects and clinical responses were evaluated in comparison
      with a group of 22 historical controls treated with TAE but without DC transfer.
      OK432 stimulation of immature DCs promoted their maturation towards cells with
      activated phenotypes, high expression of a homing receptor, fairly well-preserved
      phagocytic capacity, greatly enhanced cytokine production and effective
      tumoricidal activity. Administration of OK432-stimulated DCs to patients was
      found to be feasible and safe. Kaplan-Meier analysis revealed prolonged
      recurrence-free survival of patients treated in this manner compared with the
      historical controls (P = 0.046, log-rank test). The bioactivity of the
      transferred DCs was reflected in higher serum concentrations of the cytokines IL
      9, IL-15 and tumour necrosis factor-alpha and the chemokines CCL4 and CCL11.
      Collectively, this study suggests that a DC-based, active immunotherapeutic
      strategy in combination with locoregional treatments exerts beneficial anti
      tumour effects against liver cancer.

PMID- 21087445
TI  - Identification of a novel cell type-specific intronic enhancer of macrophage
      migration inhibitory factor (MIF) and its regulation by mithramycin.
AB  - The aim of this study was to determine the genetic regulation of macrophage
      migration inhibitory factor (MIF). DNase I hypersensitivity was used to identify
      potential hypersensitive sites (HS) across the MIF gene locus. Reporter gene
      assays were performed in different human cell lines with constructs containing
      the native or mutated HS element. Following phylogenetic and transcription factor
      binding profiling, electrophoretic mobility shift assay (EMSA) and RNA
      interference were performed and the effects of incubation with mithramycin, an
      antibiotic that binds GC boxes, were also studied. An HS centred on the first
      intron of MIF was identified. The HS acted as an enhancer in human T lymphoblasts
      (CEMC7A), human embryonic kidney cells (HEK293T) and human monocytic cells (THP
      1), but not in a fibroblast-like synoviocyte (FLS) cell line (SW982) or cultured
      FLS derived from rheumatoid arthritis (RA) patients. Two cis-elements within the
      first intron were found to be responsible for the enhancer activity. Mutation of
      the consensus Sp1 GC box on each cis-element abrogated enhancer activity and EMSA
      indicated Sp1 binding to one of the cis-elements contained in the intron. SiRNA
      knock-down of Sp1 alone or Sp1 and Sp3 together was incomplete and did not alter
      the enhancer activity. Mithramycin inhibited expression of MIF in CEMC7A cells.
      This effect was specific to the intronic enhancer and was not seen on the MIF
      promoter. These results identify a novel, cell type-specific enhancer of MIF. The
      enhancer appears to be driven by Sp1 or related Sp family members and is highly
      sensitive to inhibition via mithramycin.

PMID- 21087447
TI  - The imprecision of heterozygosity-fitness correlations hinders the detection of
      inbreeding and inbreeding depression in a threatened species.
AB  - In nonpedigreed wild populations, inbreeding depression is often quantified
      through the use of heterozygosity-fitness correlations (HFCs), based on molecular
      estimates of relatedness. Although such correlations are typically interpreted as
      evidence of inbreeding depression, by assuming that the marker heterozygosity is
      a proxy for genome-wide heterozygosity, theory predicts that these relationships
      should be difficult to detect. Until now, the vast majority of empirical research
      in this area has been performed on generally outbred, nonbottlenecked
      populations, but differences in population genetic processes may limit
      extrapolation of results to threatened populations. Here, we present an analysis
      of HFCs, and their implications for the interpretation of inbreeding, in a free
      ranging pedigreed population of a bottlenecked species: the endangered takahe
      (Porphyrio hochstetteri). Pedigree-based inbreeding depression has already been
      detected in this species. Using 23 microsatellite loci, we observed only weak
      evidence of the expected relationship between multilocus heterozygosity and
      fitness at individual life-history stages (such as survival to hatching and
      fledging), and parameter estimates were imprecise (had high error). Furthermore,
      our molecular data set could not accurately predict the inbreeding status of
      individuals (as 'inbred' or 'outbred', determined from pedigrees), nor could we
      show that the observed HFCs were the result of genome-wide identity
      disequilibrium. These results may be attributed to high variance in
      heterozygosity within inbreeding classes. This study is an empirical example from
      a free-ranging endangered species, suggesting that even relatively large numbers
      (>20) of microsatellites may give poor precision for estimating individual genome
      wide heterozygosity. We argue that pedigree methods remain the most effective
      method of quantifying inbreeding in wild populations, particularly those that
      have gone through severe bottlenecks.

PMID- 21087446
TI  - Increased numbers of immature plasma cells in peripheral blood specifically
      overexpress chemokine receptor CXCR3 and CXCR4 in patients with ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disease featuring
      infiltration by plasma cells producing immunoglobulins. We have reported
      previously the specific and significant proliferation of immature plasma cells in
      the inflamed colonic and pouch mucosa of UC patients. The aim of this study was
      to characterize peripheral blood immature plasma cells and the migration
      mechanisms of such immature plasma cells to inflamed sites in UC. The
      characteristics of peripheral blood immature plasma cells and chemokine receptor
      expression were examined by flow cytometry. Expression of mucosal chemokine was
      quantified using real-time reverse transcription-polymerase chain reaction and
      immunohistochemistry. The number of peripheral blood immature plasma cells was
      significantly higher in patients with active UC and active Crohn's disease (CD)
      than in healthy controls. The proportion of immature plasma cells was correlated
      positively with clinical activities of UC and CD. Many peripheral blood immature
      plasma cells were positive for CXCR3, CXCR4, CCR9 and CCR10. Expression of CXCR3
      and CXCR4 in UC patients was significantly higher than in controls. CXCL9, CXCL10
      and CXCL11 mRNA levels in colonic mucosa of inflamed IBD were higher than in
      controls. Immunofluorescence study also showed abundant CXCR3-positive immature
      plasma cells in the inflamed colonic mucosa of UC. Increased numbers of immature
      plasma cells may migrate towards inflammatory sites of UC via the CXCR3 axis, and
      may participate in UC pathogenesis.

PMID- 21087448
TI  - The transcriptomics of sympatric dwarf and normal lake whitefish (Coregonus
      clupeaformis spp., Salmonidae) divergence as revealed by next-generation
      sequencing.
AB  - Gene expression divergence is one of the mechanisms thought to be involved in the
      emergence of incipient species. Next-generation sequencing has become an
      extremely valuable tool for the study of this process by allowing whole
      transcriptome sequencing, or RNA-Seq. We have conducted a 454 GS-FLX
      pyrosequencing experiment to refine our understanding of adaptive divergence
      between dwarf and normal lake whitefish species (Coregonus clupeaformis spp.).
      The objectives were to: (i) investigate transcriptomic divergence as measured by
      liver RNA-Seq; (ii) test the correlation between divergence in expression and
      sequence polymorphism; and (iii) investigate the extent of allelic imbalance. We
      also compared the results of RNA-seq with those of a previous microarray study
      performed on the same fish. Following de novo assembly, results showed that
      normal whitefish overexpressed more contigs associated with protein synthesis
      while dwarf fish overexpressed more contigs related to energy metabolism,
      immunity and DNA replication and repair. Moreover, 63 SNPs showed significant
      allelic imbalance, and this phenomenon prevailed in the recently diverged dwarf
      whitefish. Results also showed an absence of correlation between gene expression
      divergence as measured by RNA-Seq and either polymorphism rate or sequence
      divergence between normal and dwarf whitefish. This study reiterates an important
      role for gene expression divergence, and provides evidence for allele-specific
      expression divergence as well as evolutionary decoupling of regulatory and coding
      sequences in the adaptive divergence of normal and dwarf whitefish. It also
      demonstrates how next-generation sequencing can lead to a more comprehensive
      understanding of transcriptomic divergence in a young species pair.

PMID- 21087449
TI  - Management of tinnitus in English NHS audiology departments: an evaluation of
      current practice.
AB  - RATIONALE, AIM AND OBJECTIVE: In 2009, the UK Department of Health formalized
      recommended National Health Service practices for the management of tinnitus from
      primary care onwards. It is timely therefore to evaluate the perceived
      practicality, utility and impact of those guidelines in the context of current
      practice. METHODS: We surveyed current practice by posting a 36-item
      questionnaire to all audiology and hearing therapy staff that we were able to
      identify as being involved in tinnitus patient care in England. RESULTS: In
      total, 138 out of 351 clinicians responded (39% response rate). The findings
      indicate a consensus opinion that management should be tailored to individual
      symptom profiles but that there is little standardization of assessment
      procedures or tools in use. CONCLUSIONS: While the lack of standardized practice
      might provide flexibility to meet local demand, it has drawbacks. It makes it
      difficult to ascertain key standards of best practice, it complicates the process
      of clinical audit, it implies unequal patient access to care, and it limits the
      implementation of translational research outcomes. We recommend that core
      elements of practice should be standardized, including use of a validated
      tinnitus questionnaires and an agreed pathway for decision making to better
      understand the rationale for management strategies offered.

PMID- 21087450
TI  - Quality of pathological reporting for renal cell cancer: implications for
      systemic therapy, prognostication and surveillance.
AB  - OBJECTIVE: * To evaluate whether current nephrectomy pathology reports are
      sufficient to allow clinicians to use prognostic nomograms, tailor surveillance,
      enroll patients into adjuvant trials and select systemic therapy for renal cell
      carcinoma (RCC). PATIENTS AND METHODS: * Nephrectomy pathology reports were
      obtained from the LA County Tumor Registry. Key reporting elements identified by
      the College of American Pathology (CAP) and utilized in RCC prognostic models
      were abstracted. Hospital type was coded as community, teaching or cancer centre.
      * Reporting quality was assessed across hospital type and year. RESULTS: * A
      total of 317 of 344 sampled reports (92.2%) met the inclusion criteria. Tumour
      size and margin status were commonly reported. Some 90.2% and 84.2% of reports
      provided data on histology and Fuhrman grade. Tumour classification was omitted
      in 27.8%. * Microvascular invasion and necrosis were infrequently reported (44.5%
      and 25.6%, respectively). Only 59.9% of reports met CAP guidelines for tumour
      classification, margin, size, histology and grade. * Two prognostic nomograms
      (Stage, Size, Grade and Necrosis system and Kattan) could rarely be utilized
      (15.8% and 12.3%, respectively), whereas the UCLA Integrated Staging System could
      be used frequently (65.6%). There were discrepancies satisfying CAP guidelines
      between community, teaching and cancer centre hospitals, with 54.7%, 70.5% and
      75% of reports meeting CAP criteria (P= 0.0102). CONCLUSIONS: * Current RCC
      pathology reporting fails to satisfy CAP guidelines, does not permit the use of
      prognostic systems, and may hinder enrollment into adjuvant trials and the
      selection of systemic therapy. Important reporting discrepancies exist between
      hospital types, with cancer centres performing best. * Quality improvement
      initiatives to encourage consistent, comprehensive and clinically relevant
      pathology reports would improve the quality of RCC patient care.

PMID- 21087451
TI  - The role of transrectal saturation biopsy in tumour localization: pathological
      correlation after retropubic radical prostatectomy and implication for focal
      ablative therapy.
AB  - OBJECTIVE: * To evaluate the accuracy of an initial 24-core prostate biopsy
      scheme (PBx24) in predicting unilateral prostate cancer (PCa) in radical
      prostatectomy (RP) specimens. PATIENTS AND METHODS: * Between 2005 and 2008, 203
      consecutive patients underwent PBx24 followed by RP for PCa. The area under the
      curve (AUC) was used to evaluate the accuracy of unilateral PCa on PBx24 to
      predict unilateral PCa in RP specimens. * The positive predictive value (PPV) and
      negative predictive value (NPV) were also calculated. Moreover, in patients with
      unilateral PCa on biopsy, univariable and multivariable logistic regression
      analyses tested the relationship between the presence of unilateral PCa in an RP
      specimen and the variables: age, prostate-specific antigen (PSA), total prostate
      volume, clinical stage, primary Gleason grade, secondary Gleason grade and the
      number of positive cores. RESULTS: * PCa cores were unilateral in 115 patients
      (56.7%) on biopsy. Of those, only 26 (22.6%) had unilateral PCa in the RP
      specimen (AUC, 72.9%; PPV, 22.6%; NPV, 98.8%). In patients with clinically low
      risk tumours, only 17 of 63 (27%) had a unilateral PCa on PBx24 and in the RP
      specimen (AUC, 59.1%; PPV, 27.0%; NPV, 100.0%). * None of the examined variables
      was an independent predictor of the presence of unilateral PCa in the RP specimen
      (all P > 0.05). CONCLUSIONS: * Initial PBx24 is not sufficiently accurate to be
      dependable as a method of predicting tumour laterality in RP specimens.
      Therefore, the use of PBx24 to guide hemi-ablation therapy of PCa may lead to
      mistreatment in a considerable proportion of patients. * Moreover, none of the
      routinely available clinical and pathological characteristics appears to improve
      the ability of unilateral PCa on biopsy to predict unilateral PCa in the RP
      specimen.

PMID- 21087452
TI  - A prospective, randomized trial comparing the Vienna nomogram to an eight-core
      prostate biopsy protocol.
AB  - OBJECTIVE: * To compare prostate cancer detection rates using the Vienna nomogram
      versus an 8-core prostate biopsy protocol. To compare the complication rates of
      transrectal prostate biopsy in the two groups. PATIENTS AND METHODS: * In a
      prospective randomized trial, men with a serum PSA >= 2.5 ng/ml were stratified
      according to serum PSA (I = PSA 2.5-10; II = PSA 10.1-30; III = PSA 30.1-50
      ng/mL) and were then randomized to group A (number of cores determined according
      to the Vienna nomogram) or group B (8-core prostate biopsy). * Statistical
      analysis was performed using Student's t-test for parametric data, Mann-Whitney
      test for nonparametric data and Fisher's exact test for contingency tables. A two
      tailed p-value <0.05 was accepted as statistically significant. RESULTS: * In the
      period July 2006 to July 2009, 303 patients were randomized to group A (n = 152)
      or group B (n = 151). There were no significant differences in serum PSA,
      prostate volume, PSA density or post-biopsy complications between the groups. *
      The cancer detection rate was lower in group A than in group B for the whole
      study cohort (35.5% vs 38.4%), for those with PSA < 10 ng/ml (28.1% vs 33%) and
      for those with prostate volume >50 ml (22% vs 25.8%). These differences were not
      statistically significant (NSS). CONCLUSION: * These findings suggest that there
      is no significant advantage in using the Vienna nomogram to determine the number
      of prostate biopsy cores to be taken, compared to an 8-core biopsy protocol.

PMID- 21087454
TI  - Hematopoietic differentiation from human ESCs as a model for developmental
      studies and future clinical translations. Invited review following the FEBS
      Anniversary Prize received on 5 July 2009 at the 34th FEBS Congress in Prague.
AB  - Human embryonic stem cells (hESCs) and induced pluripotent stem cells are
      excellent models for the study of embryonic hematopoiesis in vitro, aiding the
      design of new differentiation models that may be applicable to cell-replacement
      therapies. Adult and fetal hematopoietic stem cells are currently being used in
      biomedical applications; however, the latest advances in regenerative medicine
      and stem cell biology suggest that hESC-derived hematopoietic stem cells are an
      outstanding tool for enhancing immunotherapy and treatments for blood disorders
      and cancer, for example. In this review, we compare various methods used for
      inducing in vitro hematopoietic differentiation from hESCs, based on co-culture
      with stromal cells or formation of embryoid bodies, and analyse their ability to
      give rise to hematopoietic precursors, with emphasis on their engraftment
      potential as a measure of their functionality in vivo.

PMID- 21087453
TI  - Prognostic risk stratification of pathological stage T2N0 bladder cancer after
      radical cystectomy.
AB  - OBJECTIVE: * To stratify risk of pathological (p) T2N0 urothelial carcinoma of
      the bladder after radical cystectomy (RC) based on pathological factors to
      facilitate the development of adjuvant therapy trials for high-risk patients.
      PATIENTS AND METHODS: * The study comprised 707 patients from a database of
      patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and
      not received perioperative chemotherapy. * The effect of residual pT-stage at RC,
      age, grade, lymphovascular invasion and number of lymph nodes removed on
      recurrence-free survival was evaluated using Cox regression analyses. A weighted
      prognostic model was devised with significant variables. RESULTS: * The median
      follow up was 60.9 months. In multivariable analyses, residual disease at RC
      (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both
      compared with <pT2), high-grade (HR 2.127, P = 0.09) and lymphovascular invasion
      (HR 2.234, P < 0.001) were associated with recurrence-free survival (c = 0.70). *
      Three risk groups were devised based on weighted variables with 5-year recurrence
      free survival of 95% (95% CI 87-98), 86% (95% CI 81-90) and 62% (95% CI 54-69) in
      the good-risk, intermediate-risk and poor-risk groups, respectively (c = 0.68).
      The primary limitation is the retrospective and multicenter feature. CONCLUSIONS:
      * A prognostic risk model for patients with pT2N0 bladder cancer undergoing RC
      with generally adequate lymph node dissection was constructed based on residual
      pathological stage at RC, grade and lymphovascular invasion. * These data warrant
      validation and may enable the selection of patients with high-risk pT2N0
      urothelial carcinoma of the bladder for adjuvant therapy trials.

PMID- 21087455
TI  - Copines-1, -2, -3, -6 and -7 show different calcium-dependent intracellular
      membrane translocation and targeting.
AB  - The copines are a family of C2- and von Willebrand factor A-domain-containing
      proteins that have been proposed to respond to increases in intracellular calcium
      by translocating to the plasma membrane. The copines have been reported to
      interact with a range of cell signalling and cytoskeletal proteins, which may
      therefore be targeted to the membrane following increases in cellular calcium.
      However, neither the function of the copines, nor their actual movement to the
      plasma membrane, has been fully established in mammalian cells. Here, we show
      that copines-1, -2, -3, -6 and -7 respond differently to a methacholine-evoked
      intracellular increase in calcium in human embryonic kidney cell line-293 cells,
      and that their membrane association requires different levels of intracellular
      calcium. We demonstrate that two of these copines associate with different
      intracellular vesicles following calcium entry into cells, and identify a novel
      conserved amino acid sequence that is required for their membrane translocation
      in living cells. Our data show that the von Willebrand factor A-domain of the
      copines modulates their calcium sensitivity and intracellular targeting.
      Together, these findings suggest a different set of roles for the members of this
      protein family in mediating calcium-dependent processes in mammalian cells.

PMID- 21087457
TI  - Roles of matrix metalloproteinases in cancer progression and their
      pharmacological targeting.
AB  - Matrix metalloproteinases (MMPs) consist of a multigene family of zinc-dependent
      extracellular matrix (ECM) remodeling endopeptidases implicated in pathological
      processes, such as carcinogenesis. In this regard, their activity plays a pivotal
      role in tumor growth and the multistep processes of invasion and metastasis,
      including proteolytic degradation of ECM, alteration of the cell-cell and cell
      ECM interactions, migration and angiogenesis. The underlying premise of the
      current minireview is that MMPs are able to proteolytically process substrates in
      the extracellular milieu and, in so doing, promote tumor progression. However,
      certain members of the MMP family exert contradicting roles at different stages
      during cancer progression, depending among other factors on the tumor stage,
      tumor site, enzyme localization and substrate profile. MMPs are therefore
      amenable to therapeutic intervention by synthetic and natural inhibitors,
      providing perspectives for future studies. Multiple therapeutic agents, called
      matrix metalloproteinase inhibitors (MMPIs) have been developed to target MMPs,
      attempting to control their enzymatic activity. Even though clinical trials with
      these compounds do not show the expected results in most cases, the field of
      MMPIs is ongoing. This minireview critically evaluates the role of MMPs in
      relation to cancer progression, and highlights the challenges, as well as future
      prospects, for the design, development and efficacy of MMPIs.

PMID- 21087456
TI  - Localizing matrix metalloproteinase activities in the pericellular environment.
AB  - Matrix metalloproteinases (MMPs) are a group of structurally related proteolytic
      enzymes containing a zinc ion in the active site. They are secreted from cells or
      bound to the plasma membrane and hydrolyze extracellular matrix (ECM) and cell
      surface-bound molecules. They therefore play key roles in morphogenesis, wound
      healing, tissue repair and remodeling in diseases such as cancer and arthritis.
      Although the cell anchored membrane-type MMPs (MT-MMPs) function pericellularly,
      the secreted MMPs have been considered to act within the ECM, away from the cells
      from which they are synthesized. However, recent studies have shown that secreted
      MMPs bind to specific cell surface receptors, membrane-anchored proteins or cell
      associated ECM molecules and function pericellularly at focussed locations. This
      minireview describes examples of cell surface and pericellular partners of MMPs,
      as well as how they alter enzyme function and cellular behaviour.

PMID- 21087458
TI  - Regulation of matrix metalloproteinase activity in health and disease.
AB  - The activity of matrix metalloproteinases (MMPs) is regulated at several levels,
      including enzyme activation, inhibition, complex formation and
      compartmentalization. Regulation at the transcriptional level is also important,
      although this is not a subject of the present minireview. Most MMPs are secreted
      and have their function in the extracellular environment. This is also the case
      for the membrane-type MMPs (MT-MMPs). MMPs are also found inside cells, both in
      the nucleus, cytosol and organelles. The role of intracellular located MMPs is
      still poorly understood, although recent studies have unraveled some of their
      functions. The localization, activation and activity of MMPs are regulated by
      their interactions with other proteins, proteoglycan core proteins and/or their
      glycosaminoglycan chains, as well as other molecules. Complexes formed between
      MMPs and various molecules may also include interactions with noncatalytic sites.
      Such exosites are regions involved in substrate processing, localized outside the
      active site, and are potential binding sites of specific MMP inhibitors.
      Knowledge about regulation of MMP activity is essential for understanding various
      physiological processes and pathogenesis of diseases, as well as for the
      development of new MMP targeting drugs.

PMID- 21087459
TI  - Primate communities are structured more by dispersal limitation than by niches.
AB  - 1. A major goal in community ecology is to identify mechanisms that govern the
      assembly and maintenance of ecological communities. Current models of
      metacommunity dynamics differ chiefly in the relative emphasis placed on
      dispersal limitation and niche differentiation as causal mechanisms structuring
      ecological communities. Herein we investigate the relative roles of these two
      mechanisms in structuring primate communities in Africa, South America,
      Madagascar and Borneo. 2. We hypothesized that if dispersal limitation is
      important in structuring communities, then community similarity should depend on
      geographical proximity even after controlling for ecological similarity.
      Conversely, if communities are assembled primarily through niche processes, then
      community similarity should be determined by ecological similarity regardless of
      geographical proximity. 3. We performed Mantel and partial Mantel tests to
      investigate correlations among primate community similarity, ecological distance
      and geographical distance. Results showed significant and strongly negative
      relationships between diurnal primate community similarity and both ecological
      similarity and geographical distance in Madagascar, but significant and stronger
      negative relationships between community similarity and geographical distance in
      African, South American and Bornean metacommunities. 4. We conclude that
      dispersal limitation is an important determinant of primate community structure
      and may play a stronger role in shaping the structure of some terrestrial
      vertebrate communities than niche differentiation. These patterns are consistent
      with neutral theory. We recommend tests of functional equivalence to determine
      the extent to which neutral theory may explain primate community composition.

PMID- 21087460
TI  - How many mosquito nets are needed to achieve universal coverage? Recommendations
      for the quantification and allocation of long-lasting insecticidal nets for mass
      campaigns.
AB  - BACKGROUND: Long-lasting insecticidal nets are an effective tool for malaria
      prevention, and "universal coverage" with such nets is increasingly the goal of
      national malaria control programmes. However, national level campaigns in several
      countries have run out of nets in the course of distribution, indicating a
      problem in the method used to estimate the quantity needed. PRESENTATION OF
      HYPOTHESIS: A major reason for the shortfall in estimation is the mismatch
      between the quantification factor used to plan procurement and the allocation
      algorithm used at community level, in particular the effect of needing to add an
      additional net to households with an odd number of inhabitants. To solve this
      problem a revised quantification factor is suggested. TESTING HYPOTHESIS: Based
      on data from a broad range of household surveys across Africa, the effect of odd
      numbered households on numbers of nets distributed is estimated via two
      frequently used allocation methods. The impact of these algorithms on the
      proportion of households reaching a person to net ratio of 2:1, a frequently used
      marker of universal coverage is then calculated. IMPLICATIONS: In order to avoid
      stock-outs of nets during national coverage campaigns, it is recommended to use a
      quantification factor of 1.78 people per net, with an additional allocation
      factor suggested to account for other common problems at the community level
      resulting in a final recommended ratio of 1.60 people per net. It is also
      recommend that community level allocation procedures be aligned with procurement
      estimates to reduce shortages of nets during campaign distributions. These
      analyses should enable programme managers to make evidence-based decisions and
      support a more efficient and effective use of LLIN distribution campaign
      resources.

PMID- 21087463
TI  - Management of irritable bowel syndrome in primary care: feasibility randomised
      controlled trial of mebeverine, methylcellulose, placebo and a patient self
      management cognitive behavioural therapy website. (MIBS trial).
AB  - BACKGROUND: IBS affects 10-22% of the UK population. Abdominal pain, bloating and
      altered bowel habit affect quality of life, social functioning and time off work.
      Current GP treatment relies on a positive diagnosis, reassurance, lifestyle
      advice and drug therapies, but many suffer ongoing symptoms.A recent Cochrane
      review highlighted the lack of research evidence for IBS drugs. Neither GPs, nor
      patients have good evidence to inform prescribing decisions. However, IBS drugs
      are widely used: In 2005 the NHS costs were nearly L10 million for mebeverine and
      over L8 million for fibre-based bulking agents. CBT and self-management can be
      helpful, but poor availability in the NHS restricts their use. We have developed
      a web-based CBT self-management programme, Regul8, based on an existing evidence
      based self-management manual and in partnership with patients. This could
      increase access with minimal increased costs. METHODS/DESIGN: The aim is to
      undertake a feasibility factorial RCT to assess the effectiveness of the commonly
      prescribed medications in UK general practice for IBS: mebeverine (anti
      spasmodic) and methylcellulose (bulking-agent) and Regul8, the CBT based self
      management website.135 patients aged 16 to 60 years with IBS symptoms fulfilling
      Rome III criteria, recruited via GP practices, will be randomised to 1 of 3
      levels of the drug condition: mebeverine, methylcellulose or placebo for 6 weeks
      and to 1 of 3 levels of the website condition, Regul8 with a nurse telephone
      session and email support, Regul8 with minimal email support, or no website, thus
      creating 9 groups. OUTCOMES: Irritable bowel symptom severity scale and IBS-QOL
      will be measured at baseline, 6 and 12 weeks as the primary outcomes. An
      intention to treat analysis will be undertaken by ANCOVA for a factorial trial.
      DISCUSSION: This pilot will provide valuable information for a larger trial.
      Determining the effectiveness of commonly used drug treatments will help patients
      and doctors make informed treatment decisions regarding drug management of IBS
      symptoms, enabling better targeting of treatment. A web-based self-management CBT
      programme for IBS developed in partnership with patients has the potential to
      benefit large numbers of patients with low cost to the NHS. Assessment of the
      amount of email or therapist support required for the website will enable
      economic analysis to be undertaken.

PMID- 21087462
TI  - Prediction of conformational changes by single mutation in the hepatitis B virus
      surface antigen (HBsAg) identified in HBsAg-negative blood donors.
AB  - BACKGROUND: Selection of hepatitis B virus (HBV) by host immunity has been
      suggested to give rise to variants with amino acid substitutions at or around the
      'a' determinant of the surface antigen (HBsAg), the main target of antibody
      neutralization and diagnostic assays. However, there have never been successful
      attempts to provide evidence for this hypothesis, partly because the 3 D
      structure of HBsAg molecules has not been determined. Tertiary structure
      prediction of HBsAg solely from its primary amino acid sequence may reveal the
      molecular energetic of the mutated proteins. We carried out this preliminary
      study to analyze the predicted HBsAg conformation changes of HBV variants
      isolated from Indonesian blood donors undetectable by HBsAg assays and its
      significance, compared to other previously-reported variants that were associated
      with diagnostic failure. RESULTS: Three HBV variants (T123A, M133L and T143M) and
      a wild type sequence were analyzed together with frequently emerged variants
      T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for
      calculating antigenic index, the first two amino acid substitutions resulted in
      slight changes in the antigenicity of the 'a' determinant, while all four of the
      comparative variants showed relatively more significant changes. In the pattern
      T143M, changes in antigenic index were more significant, both in its coverage and
      magnitude, even when compared to variant T143L. These data were also partially
      supported by the tertiary structure prediction, in which the pattern T143M showed
      larger shift in the HBsAg second loop structure compared to the others.
      CONCLUSIONS: Single amino acid substitutions within or near the 'a' determinant
      of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown
      by both its antigenic index and predicted 3 D conformation. Findings in this
      study emphasize the significance of variant T143M, the prevalent isolate with
      highest degree of antigenicity changes found in Indonesian blood donors. This
      highlights the importance of evaluating the effects of protein structure
      alterations on the sensitivity of screening methods being used in detection of
      ongoing HBV infection, as well as the use of vaccines and immunoglobulin therapy
      in contributing to the selection of HBV variants.

PMID- 21087461
TI  - Insights into the role of differential gene expression on the ecological
      adaptation of the snail Littorina saxatilis.
AB  - BACKGROUND: In the past 40 years, there has been increasing acceptance that
      variation in levels of gene expression represents a major source of evolutionary
      novelty. Gene expression divergence is therefore likely to be involved in the
      emergence of incipient species, namely, in a context of adaptive radiation. In
      this study, a genome-wide expression profiling approach (cDNA-AFLP), validated by
      quantitative real-time polymerase chain reaction (qPCR) were used to get insights
      into the role of differential gene expression on the ecological adaptation of the
      marine snail Littorina saxatilis. This gastropod displays two sympatric ecotypes
      (RB and SU) which are becoming one of the best studied systems for ecological
      speciation. RESULTS: Among the 99 transcripts shared between ecotypes, 12.12%
      showed significant differential expression. At least 4% of these transcripts
      still displayed significant differences after correction for multiple tests,
      highlighting that gene expression can differ considerably between subpopulations
      adapted to alternative habitats in the face of gene flow. One of the transcripts
      identified was Cytochrome c Oxidase subunit I (COI). In addition, 6 possible
      reference genes were validated to normalize and confirm this result using qPCR.
      alpha-Tubulin and histone H3.3 showed the more stable expression levels, being
      therefore chosen as the best option for normalization. The qPCR analysis
      confirmed a higher COI expression in SU individuals. CONCLUSIONS: At least 4% of
      the transcriptome studied is being differentially expressed between ecotypes
      living in alternative habitats, even when gene flow is still substantial between
      ecotypes. We could identify a candidate transcript of such ecotype
      differentiation: Cytochrome c Oxidase Subunit I (COI), a mitochondrial gene
      involved in energy metabolism. Quantitative PCR was used to confirm the
      differences found in COI and its over-expression in the SU ecotype.
      Interestingly, COI is involved in the oxidative phosphorylation, suggesting an
      enhanced mitochondrial gene expression (or increased number of mitochondria) to
      improve energy supply in the ecotype subjected to the strongest wave action.

PMID- 21087464
TI  - Semi-automatic identification of punching areas for tissue microarray building:
      the tubular breast cancer pilot study.
AB  - BACKGROUND: Tissue MicroArray technology aims to perform immunohistochemical
      staining on hundreds of different tissue samples simultaneously. It allows faster
      analysis, considerably reducing costs incurred in staining. A time consuming
      phase of the methodology is the selection of tissue areas within paraffin blocks:
      no utilities have been developed for the identification of areas to be punched
      from the donor block and assembled in the recipient block. RESULTS: The presented
      work supports, in the specific case of a primary subtype of breast cancer
      (tubular breast cancer), the semi-automatic discrimination and localization
      between normal and pathological regions within the tissues. The diagnosis is
      performed by analysing specific morphological features of the sample such as the
      absence of a double layer of cells around the lumen and the decay of a regular
      glands-and-lobules structure. These features are analysed using an algorithm
      which performs the extraction of morphological parameters from images and
      compares them to experimentally validated threshold values. Results are
      satisfactory since in most of the cases the automatic diagnosis matches the
      response of the pathologists. In particular, on a total of 1296 sub-images
      showing normal and pathological areas of breast specimens, algorithm accuracy,
      sensitivity and specificity are respectively 89%, 84% and 94%. CONCLUSIONS: The
      proposed work is a first attempt to demonstrate that automation in the Tissue
      MicroArray field is feasible and it can represent an important tool for
      scientists to cope with this high-throughput technique.

PMID- 21087466
TI  - Validation of population-based disease simulation models: a review of concepts
      and methods.
AB  - BACKGROUND: Computer simulation models are used increasingly to support public
      health research and policy, but questions about their quality persist. The
      purpose of this article is to review the principles and methods for validation of
      population-based disease simulation models. METHODS: We developed a comprehensive
      framework for validating population-based chronic disease simulation models and
      used this framework in a review of published model validation guidelines. Based
      on the review, we formulated a set of recommendations for gathering evidence of
      model credibility. RESULTS: Evidence of model credibility derives from examining:
      1) the process of model development, 2) the performance of a model, and 3) the
      quality of decisions based on the model. Many important issues in model
      validation are insufficiently addressed by current guidelines. These issues
      include a detailed evaluation of different data sources, graphical representation
      of models, computer programming, model calibration, between-model comparisons,
      sensitivity analysis, and predictive validity. The role of external data in model
      validation depends on the purpose of the model (e.g., decision analysis versus
      prediction). More research is needed on the methods of comparing the quality of
      decisions based on different models. CONCLUSION: As the role of simulation
      modeling in population health is increasing and models are becoming more complex,
      there is a need for further improvements in model validation methodology and
      common standards for evaluating model credibility.

PMID- 21087465
TI  - Classification of rice (Oryza sativa L. Japonica nipponbare) immunophilins
      (FKBPs, CYPs) and expression patterns under water stress.
AB  - BACKGROUND: FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant
      and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase
      (PPIase) superfamily, which regulate much of metabolism through a chaperone or an
      isomerization of proline residues during protein folding. They are collectively
      referred to as immunophilin (IMM), being present in almost all cellular organs.
      In particular, a number of IMMs relate to environmental stresses. RESULTS: FKBP
      and CYP proteins in rice (Oryza sativa cv. Japonica) were identified and
      classified, and given the appropriate name for each IMM, considering the ortholog
      relation with Arabidopsis and Chlamydomonas or molecular weight of the proteins.
      29 FKBP and 27 CYP genes can putatively be identified in rice; among them, a
      number of genes can be putatively classified as orthologs of Arabidopsis IMMs.
      However, some genes were novel, did not match with those of Arabidopsis and
      Chlamydomonas, and several genes were paralogs by genetic duplication. Among 56
      IMMs in rice, a significant number are regulated by salt and/or desiccation
      stress. In addition, their expression levels responding to the water-stress have
      been analyzed in different tissues, and some subcellular IMMs located by means of
      tagging with GFP protein. CONCLUSION: Like other green photosynthetic organisms
      such as Arabidopsis (23 FKBPs and 29 CYPs) and Chlamydomonas (23 FKBs and 26
      CYNs), rice has the highest number of IMM genes among organisms reported so far,
      suggesting that the numbers relate closely to photosynthesis. Classification of
      the putative FKBPs and CYPs in rice provides the information about their
      evolutional/functional significance when comparisons are drawn with the
      relatively well studied genera, Arabidopsis and Chlamydomonas. In addition, many
      of the genes upregulated by water stress offer the possibility of manipulating
      the stress responses in rice.

PMID- 21087468
TI  - Using mammographic density to predict breast cancer risk: dense area or
      percentage dense area.
AB  - INTRODUCTION: Mammographic density (MD) is one of the strongest risk factors for
      breast cancer. It is not clear whether this association is best expressed in
      terms of absolute dense area or percentage dense area (PDA). METHODS: We measured
      MD, including nondense area (here a surrogate for weight), in the mediolateral
      oblique (MLO) mammogram using a computer-assisted thresholding technique for 634
      cases and 1,880 age-matched controls from the Cambridge and Norwich Breast
      Screening programs. Conditional logistic regression was used to estimate the risk
      of breast cancer, and fits of the models were compared using likelihood ratio
      tests and the Bayesian information criteria (BIC). All P values were two-sided.
      RESULTS: Square-root dense area was the best single predictor (for example, chi12
      = 53.2 versus 44.4 for PDA). Addition of PDA and/or square-root nondense area did
      not improve the fit (both P > 0.3). Addition of nondense area improved the fit of
      the model with PDA (chi12 = 11.6; P < 0.001). According to the BIC, the PDA and
      nondense area model did not provide a better fit than the dense area alone model.
      The fitted values of the two models were highly correlated (r = 0.97). When a
      measure of body size is included with PDA, the predicted risk is almost identical
      to that from fitting dense area alone. CONCLUSIONS: As a single parameter, dense
      area provides more information than PDA on breast cancer risk.

PMID- 21087467
TI  - Knowledge of general practitioners about nasopharyngeal cancer at the Puskesmas
      in Yogyakarta, Indonesia.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the leading causes of cancer
      death in Indonesia. At initial diagnosis, 80% of the patients present with
      advanced stage disease. In Indonesia, primary medical care is generally provided
      by the health care centres; named Puskesmas. The lack of knowledge of various
      aspects of NPC of the General practitioners (GPs) working in these centers might
      contribute to the diagnostic delay. The aim of this study was to assess the
      knowledge of these GPs on different aspects of NPC including symptoms, risk
      factors and incidence. METHODS: One hundred six GPs in the Puskesmas in the
      Yogyakarta province were subjected to a questionnaire on different aspects of NPC
      based on literature and interviews with Head and Neck Surgeons. RESULTS: All GPs
      approached participated and in total 106 questionnaires were filled in. All
      participants were aware of NPC as a disease and 89% confirmed that it is a
      serious problem in Indonesia. However, 50% of the participants believed NPC has a
      low incidence in their region. The question on early symptoms gave a mean 4.2
      answers of which 50% were incorrect.The GPs provided a total of 318 answers when
      asked for the risk factors of NPC, 75% of which were incorrect. Fifty seven GPs
      (54%) stated that they did not receive sufficient education on NPC at the
      university and insufficient knowledge was gained during daily practice. Ninety
      two percent of the GPs were interested in additional education, preferably in
      form of lectures, meetings or folders. CONCLUSION: This study revealed that GPs
      in the Puskesmas in Yogyakarta lack knowledge on all aspects of NPC. This is an
      important finding as NPC is endemic in Indonesia and the Puskesmas are the
      institutions which provide primary medical health care in the country. Further
      education of the GPs in these endemic areas could be a first step to increase the
      rate of early detection. Therefore, we suggest 1) to conduct a medical awareness
      campaign for GPs on the most important subjects concerning NPC, and 2) as soon as
      NPC awareness among GPs has risen, provide further education on the risk factors,
      the early symptoms and the incidence, education to the community. We propose to
      extend this study to other areas in Indonesia (i.e. Jakarta, Surabaya, Central
      Java), using models that have been developed in Yogyakarta.

PMID- 21087469
TI  - Developing a computer delivered, theory based intervention for guideline
      implementation in general practice.
AB  - BACKGROUND: Non-adherence to clinical guidelines has been identified as a
      consistent finding in general practice. The purpose of this study was to develop
      theory-informed, computer-delivered interventions to promote the implementation
      of guidelines in general practice. Specifically, our aim was to develop computer
      delivered prompts to promote guideline adherence for antibiotic prescribing in
      respiratory tract infections (RTIs), and adherence to recommendations for
      secondary stroke prevention. METHODS: A qualitative design was used involving 33
      face-to-face interviews with general practitioners (GPs). The prompts used in the
      interventions were initially developed using aspects of social cognitive theory,
      drawing on nationally recommended standards for clinical content. The prompts
      were then presented to GPs during interviews, and iteratively modified and
      refined based on interview feedback. Inductive thematic analysis was employed to
      identify responses to the prompts and factors involved in the decision to use
      them. RESULTS: GPs reported being more likely to use the prompts if they were
      perceived as offering support and choice, but less likely to use them if they
      were perceived as being a method of enforcement. Attitudes towards using the
      prompts were also related to anticipated patient outcomes, individual prescriber
      differences, accessibility and presentation of prompts and acceptability of
      guidelines. Comments on the prompts were largely positive after modifying them
      based on participant feedback. CONCLUSIONS: Acceptability and satisfaction with
      computer-delivered prompts to follow guidelines may be increased by working with
      practitioners to ensure that the prompts will be perceived as valuable tools that
      can support GPs' practice.

PMID- 21087470
TI  - Brake response time before and after total knee arthroplasty: a prospective
      cohort study.
AB  - BACKGROUND: Although the numbers of total knee arthroplasty (TKA) are increasing,
      there is only a small number of studies investigating driving safety after TKA.
      The parameter 'Brake Response Time (BRT)' is one of the most important criteria
      for driving safety and was therefore chosen for investigation.The present study
      was conducted to test the hypotheses that patients with right- or left-sided TKA
      show a significant increase in BRT from pre-operative (pre-op, 1 day before
      surgery) to post-operative (post-op, 2 weeks post surgery), and a significant
      decrease in BRT from post-op to the follow-up investigation (FU, 8 weeks post
      surgery). Additionally, it was hypothesized that the BRT of patients after TKA is
      significantly higher than that of healthy controls. METHODS: 31 of 70 consecutive
      patients (mean age 65.7 +/- 10.2 years) receiving TKA were tested for their BRT
      pre-op, post-op and at FU. BRT was assessed using a custom-made driving
      simulator. We used normative BRT data from 31 healthy controls for comparison.
      RESULTS: There were no significant increases between pre-op and post-op BRT
      values for patients who had undergone left- or right-sided TKA. Even the
      proportion of patients above a BRT threshold of 700 ms was not significantly
      increased postop. Controls had a BRT which was significantly better than the BRT
      of patients with right- or left-sided TKA at all three time points. CONCLUSION:
      The present study showed a small and insignificant postoperative increase in the
      BRT of patients who had undergone right- or left-sided TKA. Therefore, we believe
      it is not justified to impair the patient's quality of social and occupational
      life post-surgery by imposing restrictions on driving motor vehicles beyond an
      interval of two weeks after surgery.

PMID- 21087471
TI  - Analysis of the dihydrofolate reductase-thymidylate synthase gene sequences in
      Plasmodium vivax field isolates that failed chloroquine treatment.
AB  - BACKGROUND: To use pyrimethamine as an alternative anti-malarial drug for
      chloroquine-resistant malaria parasites, it was necessary to determine the
      enzyme's genetic variation in dihydrofolate reductase-thymidylate syntase (DHFR
      TS) among Korean strains. METHODS: Genetic variation of dhfr-ts genes of
      Plasmodium vivax clinical isolates from patients who did not respond to drug
      treatment (n = 11) in Korea were analysed. The genes were amplified using the
      polymerase chain reaction (PCR) with genomic DNA as a template. RESULTS: Sequence
      analysis showed that the open reading frame (ORF) of 1,857 nucleotides encoded a
      deduced protein of 618 amino acids (aa). Alignment with the DHFR-TS genes of
      other malaria parasites showed that a 231-residue DHFR domain and a 286-residue
      TS domain were seperated by a 101-aa linker region. This ORF shows 98.7% homology
      with the P. vivax Sal I strain (XM001615032) in the DHFR domain, 100% in the
      linker region and 99% in the TS domain. Comparison of the DHFR sequences from
      pyrimethamine-sensitive and pyrimethamine-resistant P. vivax isolates revealed
      that nine isolates belonged to the sensitive strain, whereas two isolates met the
      criteria for resistance. In these two isolates, the amino acid at position 117 is
      changed from serine to asparagine (S117N). Additionally, all Korean isolates
      showed a deletion mutant of THGGDN in short tandem repetitive sequences between
      88 and 106 amino acid. CONCLUSIONS: These results suggest that sequence
      variations in the DHFR-TS represent the prevalence of antifolate-resistant P.
      vivax in Korea. Two of 11 isolates have the Ser to Asn mutation in codon 117,
      which is the major determinant of pyrimethamine resistance in P. vivax.
      Therefore, the introduction of pyrimethamine for the treatment of chloroquine
      resistant vivax malaria as alternative drug in Korea should be seriously
      considered.

PMID- 21087472
TI  - Acute pancreatitis with organ dysfunction associates with abnormal blood
      lymphocyte signaling: controlled laboratory study.
AB  - INTRODUCTION: Severe acute pancreatitis is associated with systemic inflammation,
      compensatory immune suppression, secondary infections, vital organ dysfunction,
      and death.Our study purpose was to delineate signaling profiles of circulating
      lymphocytes in acute pancreatitis complicated by organ dysfunction. METHODS:
      Sixteen patients with acute pancreatitis, dysfunction of vital organ(s), and
      immune suppression (proportion of HLA-DR Human Leukocyte Antigen - DR - positive
      monocytes < 80%) participated. Healthy volunteers served as reference subjects.
      Using phospho-specific whole blood flow cytometry we studied lymphocyte
      phosphorylation of nuclear factor-kappaB (NFkappaB), mitogen-activated protein
      kinases p38 and extracellular signal-regulated kinases (ERK)1/2, and signal
      transducers and activators of transcription (STATs) 1, 3, and 6. Statistical
      comparisons were performed with the Wilcoxon-Mann-Whitney test. RESULTS: In blood
      samples supplemented with tumor necrosis factor, E. coli or S. aureus,
      phosphorylation levels of NFkappaB were lower and levels of p38 were higher in
      patients with acute pancreatitis than healthy subjects. Low NFkappaB activation
      involved CD3+CD4+ and CD3+CD8+ lymphocytes. ERK1/2 phosphorylation induced by co
      stimulation with phorbol 12-myristate 13-acetate and calcium ionophore A23187 was
      depressed in patients. STAT3 was constitutively activated in patients' CD3+CD4+
      and CD3+CD8+ lymphocytes. Also, IL-6-induced STAT1 phosphorylation was impaired
      while IL-4-induced STAT6 phosphorylation was enhanced. CONCLUSIONS: Lymphocytes
      of patients with acute pancreatitis, organ dysfunction and immune suppression
      show impaired NFkappaB activation, which increases infection risk and enhanced
      p38 activation, which sustains inflammation. Secondly, they indicate constitutive
      STAT3 activation, which may favor Th17 lineage of CD4+ lymphocyte
      differentiation. Thirdly, they reveal impaired STAT1 activation and enhanced
      STAT6 activation, denoting a shift from Th1 towards Th2 differentiation.

PMID- 21087473
TI  - Functional dissection of the alphavirus capsid protease: sequence requirements
      for activity.
AB  - BACKGROUND: The alphavirus capsid is multifunctional and plays a key role in the
      viral life cycle. The nucleocapsid domain is released by the self-cleavage
      activity of the serine protease domain within the capsid. All alphaviruses
      analyzed to date show this autocatalytic cleavage. Here we have analyzed the
      sequence requirements for the cleavage activity of Chikungunya virus capsid
      protease of genus alphavirus. RESULTS: Amongst alphaviruses, the C-terminal amino
      acid tryptophan (W261) is conserved and found to be important for the cleavage.
      Mutating tryptophan to alanine (W261A) completely inactivated the protease. Other
      amino acids near W261 were not having any effect on the activity of this
      protease. However, serine protease inhibitor AEBSF did not inhibit the activity.
      Through error-prone PCR we found that isoleucine 227 is important for the
      effective activity. The loss of activity was analyzed further by molecular
      modelling and comparison of WT and mutant structures. It was found that lysine
      introduced at position 227 is spatially very close to the catalytic triad and may
      disrupt electrostatic interactions in the catalytic site and thus inactivate the
      enzyme. We are also examining other sequence requirements for this protease
      activity. CONCLUSIONS: We analyzed various amino acid sequence requirements for
      the activity of ChikV capsid protease and found that amino acids outside the
      catalytic triads are important for the activity.

PMID- 21087474
TI  - Effects of general practitioner training and family support services on the care
      of home-dwelling dementia patients--results of a controlled cluster-randomized
      study.
AB  - BACKGROUND: More than 90% of dementia patients are cared for by their general
      practitioners, who are decisively involved in the diagnosis, therapy and
      recommendation of support services. OBJECTIVE: To test whether special training
      of general practitioners alters the care of dementia patients through their
      systematic recommendation of caregiver counseling and support groups. METHOD: 129
      general practitioners enrolled 390 dementia patients and their informal
      caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A
      constituted usual care, in Arm B and C support groups and caregiver counseling
      (in Arm B one year after baseline, in Arm C at baseline) were recommended by the
      general practitioners. The general practitioners received arm-specific training.
      Diagnostic and therapeutic behavior of physicians was recorded at baseline.
      Informal caregivers were questioned in follow-up after 2 years about the
      utilization of support services. RESULTS: The diagnostic behavior of the general
      practitioners conforms to relevant guidelines. The procedure in newly-diagnosed
      patients does not differ from previously diagnosed patients with the exception of
      the rate of referral to a specialist. About one-third of the newly-diagnosed
      dementia patients are given an anti-dementia drug. The utilization of support
      groups and counseling increased five- and fourfold, respectively. Utilization of
      other support services remained low (< 10%), with the exception of home nursing
      and institutional short-term nursing. CONCLUSION: Trained general practitioners
      usually act in conformity with guidelines with respect to diagnosing dementia,
      and partly in conformity with the guidelines with respect to recommended drug
      therapy. Recommendations of support services for informal caregivers by the
      general practitioner are successful. They result in a marked increase in the
      utilization rate for the recommended services compared to offers which are not
      recommended by the general practitioner. TRIAL REGISTRATION: ISRCTN68329593.

PMID- 21087475
TI  - Contribution of diet and major depression to incidence of acute myocardial
      infarction (AMI).
AB  - BACKGROUND: Despite significant improvements in the treatment of coronary heart
      disease (CHD), it is still a major cause of mortality and morbidity among the
      Iranian population. Epidemiological studies have documented that risk factors
      including smoking and the biochemical profile are responsible for the development
      of acute myocardial infarction (AMI). Psychological factors have been discussed
      as potential risk factors for coronary heart disease. Among emotional factors,
      depression correlates with coronary heart disease, particularly myocardial
      infarction. METHODS: This case-control study was conducted on 120 cases (69 males
      and 51 females) of acute myocardial infarction (AMI) and 120 controls, with a
      mean age of 62.48 +/- 15.39 years. Cases and controls were matched by age,
      residence and sex. RESULTS: The results revealed that severe depression was
      independently associated with the risk of AMI (P = 0.025, OR = 2.6, 95% CI 1.1
      5.8). The analysis of variables indicated that risk factors for developing
      depression were unmarried, low levels of polyunsaturated fatty acids (PUFAs),
      total dietary fiber (TDF) and carbohydrates. The levels of these dietary factors
      were lowest in severely depressed patients compared to those categorised as
      moderate or mild cases. Furthermore, severely depressed subjects were associated
      with higher levels of total cholesterol, high systolic blood pressure (SBP) and
      WHR. Age, income, a family history of coronary heart disease, education level,
      sex, employment and smoking were not associated with severe depression.
      CONCLUSION: The present study demonstrated that severe depression symptoms are
      independent risk factors for AMI. Furthermore, severe depression was associated
      with an unhealthy diet and AMI risk factors.

PMID- 21087476
TI  - Genome-wide promoter analysis of histone modifications in human monocyte-derived
      antigen presenting cells.
AB  - BACKGROUND: Monocyte-derived macrophages and dendritic cells (DCs) are important
      in inflammatory processes and are often used for immunotherapeutic approaches.
      Blood monocytes can be differentiated into macrophages and DCs, which is
      accompanied with transcriptional changes in many genes, including chemokines and
      cell surface markers. RESULTS: To study the chromatin modifications associated
      with this differentiation, we performed a genome wide analysis of histone H3
      trimethylation on lysine 4 (H3K4me3) and 27 (H3K27me3) as well as acetylation of
      H3 lysines (AcH3) in promoter regions. We report that both H3K4me3 and AcH3 marks
      significantly correlate with transcriptionally active genes whereas H3K27me3 mark
      is associated with inactive gene promoters. During differentiation, the H3K4me3
      levels decreased on monocyte-specific CD14, CCR2 and CX3CR1 but increased on DC
      specific TM7SF4/DC-STAMP, TREM2 and CD209/DC-SIGN genes. Genes associated with
      phagocytosis and antigen presentation were marked by H3K4me3 modifications. We
      also report that H3K4me3 levels on clustered chemokine and surface marker genes
      often correlate with transcriptional activity. CONCLUSION: Our results provide a
      basis for further functional correlations between gene expression and histone
      modifications in monocyte-derived macrophages and DCs.

PMID- 21087478
TI  - Modeling cardiac beta-adrenergic signaling with normalized-Hill differential
      equations: comparison with a biochemical model.
AB  - BACKGROUND: New approaches are needed for large-scale predictive modeling of
      cellular signaling networks. While mass action and enzyme kinetic approaches
      require extensive biochemical data, current logic-based approaches are used
      primarily for qualitative predictions and have lacked direct quantitative
      comparison with biochemical models. RESULTS: We developed a logic-based
      differential equation modeling approach for cell signaling networks based on
      normalized Hill activation/inhibition functions controlled by logical AND and OR
      operators to characterize signaling crosstalk. Using this approach, we modeled
      the cardiac beta1-adrenergic signaling network, including 36 reactions and 25
      species. Direct comparison of this model to an extensively characterized and
      validated biochemical model of the same network revealed that the new model gave
      reasonably accurate predictions of key network properties, even with default
      parameters. Normalized Hill functions improved quantitative predictions of global
      functional relationships compared with prior logic-based approaches.
      Comprehensive sensitivity analysis revealed the significant role of PKA negative
      feedback on upstream signaling and the importance of phosphodiesterases as key
      negative regulators of the network. The model was then extended to incorporate
      recently identified protein interaction data involving integrin-mediated
      mechanotransduction. CONCLUSIONS: The normalized-Hill differential equation
      modeling approach allows quantitative prediction of network functional
      relationships and dynamics, even in systems with limited biochemical data.

PMID- 21087477
TI  - A GA microsatellite in the Fli1 promoter modulates gene expression and is
      associated with systemic lupus erythematosus patients without nephritis.
AB  - INTRODUCTION: The transcription factor Fli1 is implicated in the pathogenesis of
      systemic lupus erythematosus (SLE). Recently, a GA(n) polymorphic microsatellite
      was characterized in the mouse Fli1 promoter that modulates promoter activity and
      is truncated in two lupus mouse models compared to non-autoimmune prone mice. In
      this work, we characterize a homologous GA(n) microsatellite in the human Fli1
      promoter. The purpose of this study is to determine the effect of the
      microsatellite length on Fli1 promoter activity in vitro and to determine if the
      length of the GA(n) microsatellite is associated with SLE and/or specific disease
      characteristics. METHODS: Constructs with variable lengths of the GA(n)
      microsatellite in the Fli1 promoter were generated and analyzed in
      promoter/reporter (P/R) assays in a human T cell line. Using three SLE patient
      cohorts and matched controls, microsatellite length was measured and association
      with the presence of disease and the occurrence of specific disease
      manifestations was assessed. RESULTS: P/R assays demonstrated that the presence
      of a shorter microsatellite resulted in higher Fli1 promoter activity. A
      significant association was observed in the lupus cohort SLE in Gullah Health
      (SLEIGH) between the GA(26) base pair allele and absence of nephritis.
      CONCLUSIONS: This study demonstrates that a GA(n) microsatellite in the human
      Fli1 promoter is highly polymorphic. The length of the microsatellite is
      inversely correlated to Fli1 promoter activity in a human T cell line. Although
      no association between microsatellite length and lupus was observed, an
      association between a specific microsatellite length and patients without
      nephritis in the SLEIGH cohort was observed.

PMID- 21087479
TI  - Primary retroperitoneal carcinosarcoma in a child: a case report.
AB  - Carcinosarcoma is a rare biphasic malignancy consisting of intermixed epithelial
      and mesenchymal elements. Carcinosarcoma is particularly rare among children. We
      accepted a 7 year old patient with retroperitoneal carcinosarcoma. The tumor was
      totally resected and no recurrence is found 11 months after operation.
      Literatures has been reviewed and there are few reports of primary
      retroperitoneal carcinosarcoma in children up to date. So we report the patient's
      clinical character, surgical resection, pathological and immunohistochemical
      analysis.

PMID- 21087480
TI  - Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine
      in biliary tract and gallbladder carcinomas.
AB  - BACKGROUND: Advanced biliary tract carcinomas (BTCs) have poor prognosis and
      limited therapeutic options. Therefore, it is crucial to combine standard
      therapies with molecular targeting. In this study EGFR, HER2, and their molecular
      transducers were analysed in terms of mutations, amplifications and over
      expression in a BTC case series. Furthermore, we tested the efficacy of drugs
      targeting these molecules, as single agents or in combination with gemcitabine,
      the standard therapeutic agent against BTC. METHODS: Immunohistochemistry, FISH
      and mutational analysis were performed on 49 BTC samples of intrahepatic (ICCs),
      extrahepatic (ECCs), and gallbladder (GBCs) origin. The effect on cell
      proliferation of different EGFR/HER2 pathway inhibitors as single agents or in
      combination with gemcitabine was investigated on BTC cell lines. Western blot
      analyses were performed to investigate molecular mechanisms of targeted drugs.
      RESULTS: EGFR is expressed in 100% of ICCs, 52.6% of ECCs, and in 38.5% of GBCs.
      P-MAPK and p-Akt are highly expressed in ICCs (>58% of samples), and to a lower
      extent in ECCs and GBCs (<46%), indicating EGFR pathway activation. HER2 is
      overexpressed in 10% of GBCs (with genomic amplification), and 26.3% of ECCs
      (half of which has genomic amplification). EGFR or its signal transducers are
      mutated in 26.5% of cases: 4 samples bear mutations of PI3K (8.2%), 3 cases
      (6.1%) in K-RAS, 4 (8.2%) in B-RAF, and 2 cases (4.1%) in PTEN, but no loss of
      PTEN expression is detected. EGI-1 cell line is highly sensitive to gemcitabine,
      TFK1 and TGBC1-TKB cell lines are responsive and HuH28 cell line is resistant. In
      EGI-1 cells, combination with gefitinib further increases the antiproliferative
      effect of gemcitabine. In TFK1 and TGBC1-TKB cells, the efficacy of gemcitabine
      is increased with addiction of sorafenib and everolimus. In TGBC1-TKB cells,
      lapatinib also has a synergic effect with gemcitabine. HuH28 becomes responsive
      if treated in combination with erlotinib. Moreover, HuH28 cells are sensitive to
      lapatinib as a single agent. Molecular mechanisms were confirmed by western blot
      analysis. CONCLUSION: These data demonstrate that EGFR and HER2 pathways are
      suitable therapeutic targets for BTCs. The combination of gemcitabine with drugs
      targeting these pathways gives encouraging results and further clinical studies
      could be warranted.

PMID- 21087481
TI  - Prospective case-control study of premenopausal serum estradiol and testosterone
      levels and breast cancer risk.
AB  - INTRODUCTION: Breast cancer is frequently a hormonally dependent cancer, and
      associations of circulating estrogens and androgens with subsequent breast cancer
      risk are well established in postmenopausal women. Associations of serum
      estrogens and androgens with breast cancer risk in premenopausal women are less
      well studied. The objective of this study was to determine whether estradiol and
      testosterone levels in serum collected before menopause are associated with
      subsequent breast cancer risk. METHODS: We conducted a prospective case-control
      study of 266 participants who were registered in the Columbia, Missouri, Serum
      Bank and not using exogenous hormones at the time of blood collection. Each of 98
      in situ or invasive breast cancer cases with prediagnostic serum collected before
      menopause was matched to two controls by age, date, menstrual cycle day, and time
      of day of blood collection. Estradiol and testosterone concentrations were
      quantified by using specific radioimmunoassays, and sex hormone-binding globulin
      (SHBG) was quantified with a chemiluminescent immunoassay to allow calculation of
      the non-SHBG bound hormone fractions. Data were analyzed by using conditional
      logistic regression. All tests of statistical significance were two-sided.
      RESULTS: Serum testosterone was strongly and significantly associated with breast
      cancer risk. The relative odds (OR) for increasing quartiles of total
      testosterone were 1.0, 2.1 (95% confidence interval (CI) 0.9 to 4.8), 1.5 (95%
      CI, 0.6 to 3.4), and 3.3 (95% CI, 1.5 to 7.5, P(trend) = 0.006). Comparable ORs
      for the non-SHBG bound fraction of testosterone that is bioavailable were 1.0,
      1.7 (95% CI, 0.7 to 4.2), 1.7 (95% CI, 0.7 to 4.0), and 4.2 (95% CI, 1.6 to 10.9,
      P(trend) = 0.002). Total and non-SHBG-bound estradiol were not associated with
      breast cancer, but extreme variation in levels across the menstrual cycle coupled
      with relatively small numbers, particularly for analyses stratified by cycle
      phase, limited the power to detect associations. CONCLUSIONS: Results suggest
      that premenopausal women with elevated serum testosterone levels are at an
      increased risk of breast cancer.

PMID- 21087482
TI  - Parents' beliefs about appropriate infant size, growth and feeding behaviour:
      implications for the prevention of childhood obesity.
AB  - BACKGROUND: A number of risk factors are associated with the development of
      childhood obesity which can be identified during infancy. These include infant
      feeding practices, parental response to infant temperament and parental
      perception of infant growth and appetite. Parental beliefs and understanding are
      crucial determinants of infant feeding behaviour; therefore any intervention
      would need to take account of their views. This study aimed to explore UK
      parents' beliefs concerning their infant's size, growth and feeding behaviour and
      parental receptiveness to early intervention aimed at reducing the risk of
      childhood obesity. METHOD: Six focus groups were undertaken in a range of
      different demographic localities, with parents of infants less than one year of
      age. The focus groups were audio-recorded, transcribed verbatim and thematic
      analysis applied using an interpretative, inductive approach. RESULTS: 38 parents
      (n=36 female, n=2 male), age range 19-45 years (mean 30.1 years, SD 6.28)
      participated in the focus groups. 12/38 were overweight (BMI 25-29.99) and 8/38
      obese (BMI>30). Five main themes were identified. These were a) parental concern
      about breast milk, infant contentment and growth; b) the belief that the main
      cause of infant distress is hunger is widespread and drives inappropriate
      feeding; c) rationalisation for infants' larger size; d) parental uncertainty
      about identifying and managing infants at risk of obesity and e) intentions and
      behaviour in relation to a healthy lifestyle. CONCLUSIONS: There are a number of
      barriers to early intervention with parents of infants at risk of developing
      obesity. Parents are receptive to prevention prior to weaning and need better
      support with best practice in infant feeding. In particular, this should focus on
      helping them understand the physiology of breast feeding, how to differentiate
      between infant distress caused by hunger and other causes and the timing of
      weaning. Some parents also need guidance about how to recognize and prepare
      healthy foods and facilitate physical activity for their infants.

PMID- 21087483
TI  - The effects of low frequency electrical stimulation on satellite cell activity in
      rat skeletal muscle during hindlimb suspension.
AB  - BACKGROUND: The ability of skeletal muscle to grow and regenerate is dependent on
      resident stem cells called satellite cells. It has been shown that chronic
      hindlimb unloading downregulates the satellite cell activity. This study
      investigated the role of low-frequency electrical stimulation on satellite cell
      activity during a 28 d hindlimb suspension in rats. RESULTS: Mechanical unloading
      resulted in a 44% reduction in the myofiber cross-sectional area as well as a 29%
      and 34% reduction in the number of myonuclei and myonuclear domains,
      respectively, in the soleus muscles (P < 0.001 vs the weight-bearing control).
      The number of quiescent (M-cadherin(+)), proliferating (BrdU(+) and myoD(+)), and
      differentiated (myogenin(+)) satellite cells was also reduced by 48-57% compared
      to the weight-bearing animals (P < 0.01 for all). Daily application of electrical
      stimulation (2 * 3 h at a 20 Hz frequency) partially attenuated the reduction of
      the fiber cross-sectional area, satellite cell activity, and myonuclear domain (P
      < 0.05 for all). Extensor digitorum longus muscles were not significantly altered
      by hindlimb unloading. CONCLUSION: This study shows that electrical stimulation
      partially attenuated the decrease in muscle size and satellite cells during
      hindlimb unloading. The causal relationship between satellite cell activation and
      electrical stimulation remain to be established.

PMID- 21087485
TI  - HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in
      saliva and peripheral blood among children and their mothers in the uganda sickle
      cell anemia KSHV Study.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or
      HHV8) is a gamma-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence
      rates vary geographically with variable rates recorded in different sub Sahara
      African countries, suggesting that effects of genetic and/or environmental
      factors may influence the risk of infection. One study conducted in South Africa,
      where KSHV seroprevalence is relatively low, found that carriage of human
      leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04
      was associated with increased shedding of KSHV DNA in saliva. Confirmation of
      those results would strengthen the hypothesis that genetic factors may influence
      KSHV distribution by modulating KSHV shedding in saliva. To explore these
      associations in another setting, we used high resolution HLA-A, B, and DRB1
      typing on residual samples from the Uganda Sickle Cell Anemia KSHV study,
      conducted in a high KSHV seroprevalence region, to investigate associations
      between HLA and KSHV shedding in saliva or peripheral blood among 233 children
      and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV
      shedding in our study, but our study was small and was not adequately powered to
      exclude small associations. In exploratory analyses, we found marginal
      association of KSHV DNA shedding in saliva but not in peripheral blood among
      children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in
      peripheral blood but not in saliva among children carrying HLA- B*0801 alleles.
      The contribution of individual HLA polymorphisms to KSHV shedding is important
      but it may vary in different populations. Larger population-based studies are
      needed to estimate the magnitude and direction of association of HLA with KSHV
      shedding and viral control.

PMID- 21087486
TI  - Microbiological contamination of cubicle curtains in an out-patient podiatry
      clinic.
AB  - BACKGROUND: Exposure to potential pathogens on contaminated healthcare garments
      and curtains can occur through direct or indirect contact. This study aimed to
      identify the microorganisms present on podiatry clinic curtains and measure the
      contamination pre and post a standard hospital laundry process. METHOD: Baseline
      swabs were taken to determine colony counts present on cubical curtains before
      laundering. Curtains were swabbed again immediately after, one and three weeks
      post laundering. Total colony counts were calculated and compared to baseline,
      with identification of micro-organisms. RESULTS: Total colony counts increased
      very slightly by 3% immediately after laundry, which was not statistically
      significant, and declined significantly (p = 0.0002) by 56% one-week post
      laundry. Three weeks post laundry colony counts had increased by 16%; although
      clinically relevant, this was not statistically significant. The two most
      frequent microorganisms present throughout were Coagulase Negative Staphylococcus
      and Micrococcus species. Laundering was not completely effective, as both species
      demonstrated no significant change following laundry. CONCLUSION: This work
      suggests current laundry procedures may not be 100% effective in killing all
      microorganisms found on curtains, although a delayed decrease in total colony
      counts was evident. Cubicle curtains may act as a reservoir for microorganisms
      creating potential for cross contamination. This highlights the need for
      additional cleaning methods to decrease the risk of cross infection and the
      importance of maintaining good hand hygiene.

PMID- 21087484
TI  - Immunomodulatory dietary polysaccharides: a systematic review of the literature.
AB  - BACKGROUND: A large body of literature suggests that certain polysaccharides
      affect immune system function. Much of this literature, however, consists of in
      vitro studies or studies in which polysaccharides were injected. Their
      immunologic effects following oral administration is less clear. The purpose of
      this systematic review was to consolidate and evaluate the available data
      regarding the specific immunologic effects of dietary polysaccharides. METHODS:
      Studies were identified by conducting PubMed and Google Scholar electronic
      searches and through reviews of polysaccharide article bibliographies. Only
      articles published in English were included in this review. Two researchers
      reviewed data on study design, control, sample size, results, and nature of
      outcome measures. Subsequent searches were conducted to gather information about
      polysaccharide safety, structure and composition, and disposition. RESULTS: We
      found 62 publications reporting statistically significant effects of orally
      ingested glucans, pectins, heteroglycans, glucomannans, fucoidans,
      galactomannans, arabinogalactans and mixed polysaccharide products in rodents.
      Fifteen controlled human studies reported that oral glucans, arabinogalactans,
      heteroglycans, and fucoidans exerted significant effects. Although some studies
      investigated anti-inflammatory effects, most studies investigated the ability of
      oral polysaccharides to stimulate the immune system. These studies, as well as
      safety and toxicity studies, suggest that these polysaccharide products appear to
      be largely well-tolerated. CONCLUSIONS: Taken as a whole, the oral polysaccharide
      literature is highly heterogenous and is not sufficient to support broad product
      structure/function generalizations. Numerous dietary polysaccharides,
      particularly glucans, appear to elicit diverse immunomodulatory effects in
      numerous animal tissues, including the blood, GI tract and spleen. Glucan
      extracts from the Trametes versicolor mushroom improved survival and immune
      function in human RCTs of cancer patients; glucans, arabinogalactans and
      fucoidans elicited immunomodulatory effects in controlled studies of healthy
      adults and patients with canker sores and seasonal allergies. This review
      provides a foundation that can serve to guide future research on immune
      modulation by well-characterized polysaccharide compounds.

PMID- 21087487
TI  - Identification and developmental expression of the full complement of Cytochrome
      P450 genes in Zebrafish.
AB  - BACKGROUND: Increasing use of zebrafish in drug discovery and mechanistic
      toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and
      function. CYP enzymes catalyze oxidative transformation leading to activation or
      inactivation of many endogenous and exogenous chemicals, with consequences for
      normal physiology and disease processes. Many CYPs potentially have roles in
      developmental specification, and many chemicals that cause developmental
      abnormalities are substrates for CYPs. Here we identify and annotate the full
      suite of CYP genes in zebrafish, compare these to the human CYP gene complement,
      and determine the expression of CYP genes during normal development. RESULTS:
      Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found
      also in mammals. There are 32 genes in CYP families 5 to 51, most of which are
      direct orthologs of human CYPs that are involved in endogenous functions
      including synthesis or inactivation of regulatory molecules. The high degree of
      sequence similarity suggests conservation of enzyme activities for these CYPs,
      confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase;
      CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid
      hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which
      include CYPs prominent in metabolism of drugs and pollutants, as well as of
      endogenous substrates. There are orthologous relationships for some CYP1 s and
      some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2
      genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as
      orthologous based on sequence. Analysis of shared synteny identified CYP2 gene
      clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters.
      CONCLUSIONS: Transcript profiling by microarray and quantitative PCR revealed
      that the majority of zebrafish CYP genes are expressed in embryos, with waves of
      expression of different sets of genes over the course of development. Transcripts
      of some CYP occur also in oocytes. The results provide a foundation for the use
      of zebrafish as a model in toxicological, pharmacological and chemical disease
      research.

PMID- 21087489
TI  - Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated
      neuroinflammation and reduces spontaneous recurrent seizures.
AB  - Under certain experimental conditions, neurotrophic factors may reduce
      epileptogenesis. We have previously reported that local, intrahippocampal
      supplementation of fibroblast growth factor-2 (FGF-2) and brain-derived
      neurotrophic factor (BDNF) increases neurogenesis, reduces neuronal loss, and
      reduces the occurrence of spontaneous seizures in a model of damage-associated
      epilepsy. Here, we asked if these possibly anti-epileptogenic effects might
      involve anti-inflammatory mechanisms. Thus, we used a Herpes-based vector to
      supplement FGF-2 and BDNF in rat hippocampus after pilocarpine-induced status
      epilepticus that established an epileptogenic lesion. This model causes intense
      neuroinflammation, especially in the phase that precedes the occurrence of
      spontaneous seizures. The supplementation of FGF-2 and BDNF attenuated various
      parameters of inflammation, including astrocytosis, microcytosis and IL-1beta
      expression. The effect appeared to be most prominent on IL-1beta, whose
      expression was almost completely prevented. Further studies will be needed to
      elucidate the molecular mechanism(s) for these effects, and for that on IL-1beta
      in particular. Nonetheless, the concept that neurotrophic factors affect
      neuroinflammation in vivo may be highly relevant for the understanding of the
      epileptogenic process.

PMID- 21087488
TI  - Genital herpes evaluation by quantitative TaqMan PCR: correlating single
      detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross
      sectional and longitudinal clinical data.
AB  - OBJECTIVE: To evaluate the utility of a single quantitative PCR (qPCR)
      measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens
      collected from women with predominantly chronic HSV-2 infection in assessing
      genital HSV shedding and the clinical course of genital herpes (GH) within a
      cohort with semiannual schedule of follow up and collection of specimens.
      METHODS: Two previously described methods used for detection of HSV DNA in
      mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs.
      Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV
      DNA were explored in relation to observed cross-sectional and longitudinal
      clinical data. RESULTS: The PCR assay was sensitive and reproducible with a limit
      of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples
      were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR:
      2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL
      directly correlated with the clinical signs and symptoms of presence of active
      symptomatic disease with frequent recurrences. CONCLUSION: Single qPCR
      measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection
      provided useful information for assessing GH in the setting of infrequent
      sampling of specimens. Observed positive correlation of the presence and quantity
      of HSV-2 DNA with the presence of active and more severe course of HSV-2
      infection may have clinical significance in the evaluation and management of HSV
      2 infected patients.

PMID- 21087490
TI  - The common ancestry of life.
AB  - BACKGROUND: It is common belief that all cellular life forms on earth have a
      common origin. This view is supported by the universality of the genetic code and
      the universal conservation of multiple genes, particularly those that encode key
      components of the translation system. A remarkable recent study claims to provide
      a formal, homology independent test of the Universal Common Ancestry hypothesis
      by comparing the ability of a common-ancestry model and a multiple-ancestry model
      to predict sequences of universally conserved proteins. RESULTS: We devised a
      computational experiment on a concatenated alignment of universally conserved
      proteins which shows that the purported demonstration of the universal common
      ancestry is a trivial consequence of significant sequence similarity between the
      analyzed proteins. The nature and origin of this similarity are irrelevant for
      the prediction of "common ancestry" of by the model-comparison approach. Thus,
      homology (common origin) of the compared proteins remains an inference from
      sequence similarity rather than an independent property demonstrated by the
      likelihood analysis. CONCLUSION: A formal demonstration of the Universal Common
      Ancestry hypothesis has not been achieved and is unlikely to be feasible in
      principle. Nevertheless, the evidence in support of this hypothesis provided by
      comparative genomics is overwhelming.

PMID- 21087491
TI  - Genomic evolution and complexity of the Anaphase-promoting Complex (APC) in land
      plants.
AB  - BACKGROUND: The orderly progression through mitosis is regulated by the Anaphase
      Promoting Complex (APC), a large multiprotein E3 ubiquitin ligase that targets
      key cell-cycle regulators for destruction by the 26 S proteasome. The APC is
      composed of at least 11 subunits and associates with additional regulatory
      activators during mitosis and interphase cycles. Despite extensive research on
      APC and activator functions in the cell cycle, only a few components have been
      functionally characterized in plants. RESULTS: Here, we describe an in-depth
      search for APC subunits and activator genes in the Arabidopsis, rice and poplar
      genomes. Also, searches in other genomes that are not completely sequenced were
      performed. Phylogenetic analyses indicate that some APC subunits and activator
      genes have experienced gene duplication events in plants, in contrast to animals.
      Expression patterns of paralog subunits and activators in rice could indicate
      that this duplication, rather than complete redundancy, could reflect initial
      specialization steps. The absence of subunit APC7 from the genome of some green
      algae species and as well as from early metazoan lineages, could mean that APC7
      is not required for APC function in unicellular organisms and it may be a result
      of duplication of another tetratricopeptide (TPR) subunit. Analyses of TPR
      evolution suggest that duplications of subunits started from the central domains.
      CONCLUSIONS: The increased complexity of the APC gene structure, tied to the
      diversification of expression paths, suggests that land plants developed
      sophisticated mechanisms of APC regulation to cope with the sedentary life style
      and its associated environmental exposures.

PMID- 21087492
TI  - From an electrophoretic mobility shift assay to isolated transcription factors: a
      fast genomic-proteomic approach.
AB  - BACKGROUND: Hypocrea jecorina (anamorph Trichoderma reesei) is a filamentous
      ascomycete of industrial importance due to its hydrolases (e.g., xylanases and
      cellulases). The regulation of gene expression can influence the composition of
      the hydrolase cocktail, and thus, transcription factors are a major target of
      current research. Here, we design an approach for identifying a repressor of a
      xylanase-encoding gene. RESULTS: We used streptavidin affinity chromatography to
      isolate the Xylanase promoter-binding protein 1 (Xpp1). The optimal conditions
      and templates for the chromatography step were chosen according to the results of
      an electrophoretic mobility shift assay performed under repressing conditions,
      which yielded a DNA-protein complex specific to the AGAA-box (the previously
      identified, tetranucleotide cis-acting element). After isolating AGAA-box binding
      proteins, the eluted proteins were identified with Nano-HPLC/tandem MS-coupled
      detection. We compared the identified peptides to sequences in the H. jecorina
      genome and predicted in silico the function and DNA-binding ability of the
      identified proteins. With the results from these analyses, we eliminated all but
      three candidate proteins. We verified the transcription of these candidates and
      tested their ability to specifically bind the AGAA-box. In the end, only one
      candidate protein remained. We generated this protein with in vitro translation
      and used an EMSA to demonstrate the existence of an AGAA-box-specific protein-DNA
      complex. We found that the expression of this gene is elevated under repressing
      conditions relative to de-repressing or inducing conditions. CONCLUSIONS: We
      identified a putative transcription factor that is potentially involved in
      repressing xylanase 2 expression. We also identified two additional potential
      regulatory proteins that bind to the xyn2 promoter. Thus, we succeeded in
      identifying novel, putative transcription factors for the regulation of xylanase
      expression in H. jecorina.

PMID- 21087495
TI  - Evaluation of resident attitudes and self-reported competencies in health
      advocacy.
AB  - BACKGROUND: The CanMEDS Health Advocate role, one of seven roles mandated by the
      Royal College of Physicians and Surgeons Canada, pertains to a physician's
      responsibility to use their expertise and influence to advance the wellbeing of
      patients, communities, and populations. We conducted our study to examine
      resident attitudes and self-reported competencies related to health advocacy, due
      to limited information in the literature on this topic. METHODS: We conducted a
      pilot experience with seven internal medicine residents participating in a
      community health promotion event. The residents provided narrative feedback after
      the event and the information was used to generate items for a health advocacy
      survey. Face validity was established by having the same residents review the
      survey. Content validity was established by inviting an expert physician panel to
      review the survey. The refined survey was then distributed to a cohort of core
      Internal Medicine residents electronically after attendance at an academic
      retreat teaching residents about advocacy through didactic sessions. RESULTS: The
      survey was completed by 76 residents with a response rate of 68%. The majority
      agreed to accept an advocacy role for societal health needs beyond caring for
      individual patients. Most confirmed their ability to identify health determinants
      and reaffirmed the inherent requirements for health advocacy. While involvement
      in health advocacy was common during high school and undergraduate studies, 76%
      of residents reported no current engagement in advocacy activity, and 36% were
      undecided if they would engage in advocacy during their remaining time as
      residents, fellows or staff. The common barriers reported were insufficient time,
      rest and stress. CONCLUSIONS: Medical residents endorsed the role of health
      advocate and reported proficiency in determining the medical and bio-psychosocial
      determinants of individuals and communities. Few residents, however, were
      actively involved in health advocacy beyond an individual level during residency
      due to multiple barriers. Further studies should address these barriers to
      advocacy and identify the reasons for the discordance we found between advocacy
      endorsement and lack of engagement.

PMID- 21087494
TI  - Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of
      an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in
      glutathione S-transferase in a cross-sectional study.
AB  - INTRODUCTION: A deletion polymorphism in glutathione S-transferase Mu-1 (GSTM1
      null) has previously been implicated to play a role in rheumatoid arthritis (RA)
      risk and progression, although no prior investigations have examined its
      associations with anticitrullinated protein antibody (ACPA) positivity. The
      purpose of this study was to examine the associations of GSTM1-null with ACPA
      positivity in RA and to assess for evidence of interaction between GSTM1 and HLA
      DRB1 shared epitope (SE). METHODS: Associations of GSTM1-null with ACPA
      positivity were examined separately in two RA cohorts, the Veterans Affairs
      Rheumatoid Arthritis (VARA) registry (n = 703) and the Study of New-Onset RA
      (SONORA; n = 610). Interactions were examined by calculating an attributable
      proportion (AP) due to interaction. RESULTS: A majority of patients in the VARA
      registry (76%) and SONORA (69%) were positive for ACPA with a similar frequency
      of GSTM1-null (53% and 52%, respectively) and HLA-DRB1 SE positivity (76% and
      71%, respectively). The parameter of patients who had ever smoked was more common
      in the VARA registry (80%) than in SONORA (65%). GSTM1-null was significantly
      associated with ACPA positivity in the VARA registry (odds ratio (OR), 1.45; 95%
      confidence interval (CI), 1.02 to 2.05), but not in SONORA (OR, 1.00; 95% CI,
      0.71 to 1.42). There were significant additive interactions between GSTM1 and HLA
      DRB1 SE in the VARA registry (AP, 0.49; 95% CI, 0.21 to 0.77; P < 0.001) in ACPA
      positivity, an interaction replicated in SONORA (AP, 0.38; 95% CI, 0.00 to 0.76;
      P = 0.050). CONCLUSIONS: This study is the first to show that the GSTM1-null
      genotype, a common genetic variant, exerts significant additive interaction with
      HLA-DRB1 SE on the risk of ACPA positivity in RA. Since GSTM1 has known
      antioxidant functions, these data suggest that oxidative stress may be important
      in the development of RA-specific autoimmunity in genetically susceptible
      individuals.

PMID- 21087493
TI  - Zinc in innate and adaptive tumor immunity.
AB  - Zinc is important. It is the second most abundant trace metal with 2-4 grams in
      humans. It is an essential trace element, critical for cell growth, development
      and differentiation, DNA synthesis, RNA transcription, cell division, and cell
      activation. Zinc deficiency has adverse consequences during embryogenesis and
      early childhood development, particularly on immune functioning. It is essential
      in members of all enzyme classes, including over 300 signaling molecules and
      transcription factors. Free zinc in immune and tumor cells is regulated by 14
      distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces
      cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while
      sufficient zinc levels allows maintenance of autophagy. Cancer cells have
      upregulated zinc importers, and frequently increased zinc levels, which allow
      them to survive. Based on this novel synthesis, approaches which locally regulate
      zinc levels to promote survival of immune cells and/or induce tumor apoptosis are
      in order.

PMID- 21087496
TI  - Microbicide excipients can greatly increase susceptibility to genital herpes
      transmission in the mouse.
AB  - BACKGROUND: Several active ingredients proposed as vaginal microbicides have been
      shown paradoxically to increase susceptibility to infection in mouse genital
      herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition,
      "inactive ingredients" (or excipients) used in topical products to formulate and
      deliver the active ingredient might also cause epithelial toxicities that
      increase viral susceptibility. However, excipients have not previously been
      tested in susceptibility models. METHODS: Excipients commonly used in topical
      products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or
      other formulations as specified. Twelve hours after exposure to the excipient or
      a control treatment, mice were challenged with a vaginal dose of HSV-2, and three
      days later were assessed for infection by vaginal lavage culture to assess
      susceptibility. RESULTS: The following excipients markedly increased
      susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML)
      formulated in K-Y(r) Warming Jelly, 5% GML as a colloidal suspension in phosphate
      buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent
      ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in
      the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend
      toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1%
      disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did
      not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus
      0.02% propylparaben, and 1% benzyl alcohol. CONCLUSIONS: As reported with other
      surfactants, the surfactant/emulsifier GML markedly increased susceptibility to
      HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted
      propylene glycol and PEG-8 greatly increased susceptibility.

PMID- 21087497
TI  - Cellulosic ethanol: interactions between cultivar and enzyme loading in wheat
      straw processing.
AB  - BACKGROUND: Variations in sugar yield due to genotypic qualities of feedstock are
      largely undescribed for pilot-scale ethanol processing. Our objectives were to
      compare glucose and xylose yield (conversion and total sugar yield) from straw of
      five winter wheat cultivars at three enzyme loadings (2.5, 5 and 10 FPU g-1 dm
      pretreated straw) and to compare particle size distribution of cultivars after
      pilot-scale hydrothermal pretreatment. RESULTS: Significant interactions between
      enzyme loading and cultivars show that breeding for cultivars with high sugar
      yields under modest enzyme loading could be warranted. At an enzyme loading of 5
      FPU g-1 dm pretreated straw, a significant difference in sugar yields of 17% was
      found between the highest and lowest yielding cultivars. Sugar yield from
      separately hydrolyzed particle-size fractions of each cultivar showed that finer
      particles had 11% to 21% higher yields than coarse particles. The amount of
      coarse particles from the cultivar with lowest sugar yield was negatively
      correlated with sugar conversion. CONCLUSIONS: We conclude that genetic
      differences in sugar yield and response to enzyme loading exist for wheat straw
      at pilot scale, depending on differences in removal of hemicellulose,
      accumulation of ash and particle-size distribution introduced by the
      pretreatment.

PMID- 21087498
TI  - One life ends, another begins: Management of a brain-dead pregnant mother-A
      systematic review-.
AB  - BACKGROUND: An accident or a catastrophic disease may occasionally lead to brain
      death (BD) during pregnancy. Management of brain-dead pregnant patients needs to
      follow special strategies to support the mother in a way that she can deliver a
      viable and healthy child and, whenever possible, also be an organ donor. This
      review discusses the management of brain-dead mothers and gives an overview of
      recommendations concerning the organ supporting therapy. METHODS: To obtain
      information on brain-dead pregnant women, we performed a systematic review of
      Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL).
      The collected data included the age of the mother, the cause of brain death,
      maternal medical complications, gestational age at BD, duration of extended life
      support, gestational age at delivery, indication of delivery, neonatal outcome,
      organ donation of the mothers and patient and graft outcome. RESULTS: In our
      search of the literature, we found 30 cases reported between 1982 and 2010. A
      nontraumatic brain injury was the cause of BD in 26 of 30 mothers. The maternal
      mean age at the time of BD was 26.5 years. The mean gestational age at the time
      of BD and the mean gestational age at delivery were 22 and 29.5 weeks,
      respectively. Twelve viable infants were born and survived the neonatal period.
      CONCLUSION: The management of a brain-dead pregnant woman requires a
      multidisciplinary team which should follow available standards, guidelines and
      recommendations both for a nontraumatic therapy of the fetus and for an organ
      preserving treatment of the potential donor.

PMID- 21087499
TI  - Study protocol: safety and efficacy of propranolol in newborns with Retinopathy
      of Prematurity (PROP-ROP): ISRCTN18523491.
AB  - BACKGROUND: Despite new therapeutic approaches have improved the prognosis of
      newborns with retinopathy of prematurity (ROP), an unfavourable structural and
      functional outcome still remains high. There is high pressure to develop new
      drugs to prevent and treat ROP. There is increasing enthusiasm for anti-VEGF
      drugs, but angiogenic inhibitors selective for abnormal blood vessels would be
      considered as an optimal treatment.In an animal experimental model of
      proliferative retinopathy, we have recently demonstrated that the pharmacological
      blockade of beta-adrenoreceptors improves retinal neovascularization and blood
      retinal barrier breakdown consequent to hypoxia. The purpose of this study is to
      evaluate the propranolol administration in preterm newborns suffering from a
      precocious phase of ROP in terms of safety and efficacy in counteracting the
      progression of retinopathy. METHODS/DESIGN: Preterm newborns (gestational age at
      birth lower than 32 weeks) with stage 2 ROP (zone II-III without plus) will be
      randomized, according to their gestational age, to receive propranolol added to
      standard treatment (treatment adopted by the ETROP Cooperative Group) or standard
      treatment alone. Propranolol will be administered until retinal vascularization
      will be completely developed, but not more than 90 days. Forty-four participants
      will be recruited into the study. To evaluate the safety of propranolol
      administration, cardiac and respiratory parameters will be continuously
      monitored. Blood samplings will be performed to check renal, liver and metabolic
      balance. To evaluate the efficacy of propranolol, the progression of the disease,
      the number of laser treatments or vitrectomies, the incidence of retinal
      detachment or blindness, will be evaluated by serial ophthalmologic examinations.
      Visual function will be evaluated by means of behavioural standardized tests.
      DISCUSSION: This pilot study is the first research that explores the possible
      therapeutic role of beta blockers in ROP. The objective of this research is
      highly ambitious: to find a treatment simple, inexpensive, well tolerated and
      with few adverse effects, able to counteract one of the major complications of
      the prematurity. Any favourable results of this research could open new
      perspectives and original scenarios about the treatment or the prevention of this
      and other proliferative retinopathies. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN18523491; ClinicalTrials.gov Identifier NCT01079715; EudraCT Number
      2010-018737-21.

PMID- 21087500
TI  - Molecular measurement of BCR-ABL transcript variations in chronic myeloid
      leukemia patients in cytogenetic remission.
AB  - BACKGROUND: The monitoring of BCR-ABL transcript levels by real-time quantitative
      polymerase chain reaction (RT-qPCR) has become important to assess minimal
      residual disease (MRD) and standard of care in the treatment of chronic myeloid
      leukemia (CML). In this study, we performed a prospective, sequential analysis
      using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91
      CML patients in chronic phase (CP) who achieved complete cytogenetic remission
      (CCyR) and major molecular remission (MMR) throughout imatinib treatment.
      METHODS: The absolute level of BCR-ABL transcript from peripheral blood was
      serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%,
      according to the international scale, was considered positive. Sequential
      cytogenetic analysis was also performed in bone marrow samples from all patients
      using standard protocols. RESULTS: Based on sequential analysis of BCR-ABL
      transcripts, the 91 patients were divided into three categories: (A) 57 (62.6%)
      had no variation on sequential analysis; (B) 30 (32.9%) had a single positive
      variation result obtained in a single sample; and (C) 4 (4.39%) had variations of
      BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who
      had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR
      ABL/BCR ratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a
      >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them
      showed mutations in the ABL gene. Transient cytogenetic alterations in Ph
      negative cells were observed in five (5.5%) patients, and none of whom lost CCyR.
      CONCLUSIONS: Despite an increase levels of BCR-ABL/BCR ratio variations by RT
      qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single
      variations should neither be considered predictive of subsequent failure and nor
      an indication for altering imatinib dose or switching to second generation
      therapy. Changing of imatinib on the basis of BCR-ABL/BCR% sustained increase and
      mutational studies is a prudent approach for preserving other therapeutic options
      in imatinib-resistant patients.

PMID- 21087501
TI  - Evolution of dengue virus type 3 genotype III in Venezuela: diversification,
      rates and population dynamics.
AB  - BACKGROUND: Dengue virus (DENV) is a member of the genus Flavivirus of the family
      Flaviviridae. DENV are comprised of four distinct serotypes (DENV-1 through DENV
      4) and each serotype can be divided in different genotypes. Currently, there is a
      dramatic emergence of DENV-3 genotype III in Latin America. Nevertheless, we
      still have an incomplete understanding of the evolutionary forces underlying the
      evolution of this genotype in this region of the world. In order to gain insight
      into the degree of genetic variability, rates and patterns of evolution of this
      genotype in Venezuela and the South American region, phylogenetic analysis, based
      on a large number (n = 119) of envelope gene sequences from DENV-3 genotype III
      strains isolated in Venezuela from 2001 to 2008, were performed. RESULTS:
      Phylogenetic analysis revealed an in situ evolution of DENV-3 genotype III
      following its introduction in the Latin American region, where three different
      genetic clusters (A to C) can be observed among the DENV-3 genotype III strains
      circulating in this region. Bayesian coalescent inference analyses revealed an
      evolutionary rate of 8.48 x 10-4 substitutions/site/year (s/s/y) for strains of
      cluster A, composed entirely of strains isolated in Venezuela. Amino acid
      substitution at position 329 of domain III of the E protein (A->V) was found in
      almost all E proteins from Cluster A strains. CONCLUSIONS: A significant
      evolutionary change between DENV-3 genotype III strains that circulated in the
      initial years of the introduction in the continent and strains isolated in the
      Latin American region in recent years was observed. The presence of DENV-3
      genotype III strains belonging to different clusters was observed in Venezuela,
      revealing several introduction events into this country. The evolutionary rate
      found for Cluster A strains circulating in Venezuela is similar to the others
      previously established for this genotype in other regions of the world. This
      suggests a lack of correlation among DENV genotype III substitution rate and
      ecological pattern of virus spread.

PMID- 21087502
TI  - An experimental study of pathologist's navigation patterns in virtual microscopy.
AB  - In virtual microscopy, a sequential process of captures of microscopical fields,
      allows to construct a virtual slide which is visualized using a specialized
      software, called the virtual microscopy viewer. This tool allows useful
      exploration of images, composed of thousands of microscopical fields of view at
      different levels of magnification, emulating an actual microscopical examination.
      The aim of this study was to establish the main pathologist's navigation patterns
      when exploring virtual microscopy slides, using a graphical user interface,
      adapted to the pathologist's workflow. Four pathologists with a similar level of
      experience, graduated from the same pathology program, navigated six virtual
      slides. Different issues were evaluated, namely, the percentage of common visited
      image regions, the time spent at each and its coincidence level, that is to say,
      the region of interest location. In addition, navigation patterns were also
      assessed, i.e., mouse movement velocities and linearity of the diagnostic paths.
      Results suggest that regions of interest are determined by a complex combination
      of the visited area, the time spent at each visit and the coincidence level among
      pathologists. Additionally, linear trajectories and particular velocity patterns
      were found for the registered diagnostic paths.

PMID- 21087504
TI  - Predicting genome-wide redundancy using machine learning.
AB  - BACKGROUND: Gene duplication can lead to genetic redundancy, which masks the
      function of mutated genes in genetic analyses. Methods to increase sensitivity in
      identifying genetic redundancy can improve the efficiency of reverse genetics and
      lend insights into the evolutionary outcomes of gene duplication. Machine
      learning techniques are well suited to classifying gene family members into
      redundant and non-redundant gene pairs in model species where sufficient genetic
      and genomic data is available, such as Arabidopsis thaliana, the test case used
      here. RESULTS: Machine learning techniques that combine multiple attributes led
      to a dramatic improvement in predicting genetic redundancy over single trait
      classifiers alone, such as BLAST E-values or expression correlation. In
      withholding analysis, one of the methods used here, Support Vector Machines, was
      two-fold more precise than single attribute classifiers, reaching a level where
      the majority of redundant calls were correctly labeled. Using this higher
      confidence in identifying redundancy, machine learning predicts that about half
      of all genes in Arabidopsis showed the signature of predicted redundancy with at
      least one but typically less than three other family members. Interestingly, a
      large proportion of predicted redundant gene pairs were relatively old
      duplications (e.g., Ks > 1), suggesting that redundancy is stable over long
      evolutionary periods. CONCLUSIONS: Machine learning predicts that most genes will
      have a functionally redundant paralog but will exhibit redundancy with relatively
      few genes within a family. The predictions and gene pair attributes for
      Arabidopsis provide a new resource for research in genetics and genome evolution.
      These techniques can now be applied to other organisms.

PMID- 21087505
TI  - The Rx for Change database: a first-in-class tool for optimal prescribing and
      medicines use.
AB  - BACKGROUND: Globally, suboptimal prescribing practices and medication errors are
      common. Guidance to health professionals and consumers alone is not sufficient to
      optimise behaviours, therefore strategies to promote evidence-based decision
      making and practice, such as decision support tools or reminders, are important.
      The literature in this area is growing, but is of variable quality and dispersed
      across sources, which makes it difficult to identify, access, and assess. To
      overcome these problems, by synthesizing and evaluating the data from systematic
      reviews, we have developed Rx for Change to provide a comprehensive, online
      database of the evidence for strategies to improve drug prescribing and use.
      METHODS: We use reliable and valid methods to search and screen the literature,
      and to appraise and analyse the evidence from relevant systematic reviews. We
      then present the findings in an online format which allows users to easily access
      pertinent information related to prescribing and medicines use. The database is a
      result of the collaboration between the Canadian Agency for Drugs and
      Technologies in Health (CADTH) and two Cochrane review groups. RESULTS: To
      capture the body of evidence on interventions to improve prescribing and
      medicines use, we conduct comprehensive and regular searches in multiple
      databases, and hand-searches of relevant journals. We screen articles to identify
      relevant systematic reviews, and include them if they are of moderate or high
      methodological quality. Two researchers screen, assess quality, and extract data
      on demographic details, intervention characteristics, and outcome data. We report
      the results of our analysis of each systematic review using a standardised
      quantitative and qualitative format. Rx for Change currently contains over 200
      summarised reviews, structured in a multi-level format. The reviews included in
      the database are diverse, covering various settings, conditions, or diseases and
      targeting a range of professional and consumer behaviors. CONCLUSIONS: Rx for
      Change is a novel database that synthesizes current research evidence about the
      effects of interventions to improve drug prescribing practices and medicines use.

PMID- 21087503
TI  - Hypercholesterolemia and microvascular dysfunction: interventional strategies.
AB  - Hypercholesterolemia is defined as excessively high plasma cholesterol levels,
      and is a strong risk factor for many negative cardiovascular events. Total
      cholesterol levels above 200 mg/dl have repeatedly been correlated as an
      independent risk factor for development of peripheral vascular (PVD) and coronary
      artery disease (CAD), and considerable attention has been directed toward
      evaluating mechanisms by which hypercholesterolemia may impact vascular outcomes;
      these include both results of direct cholesterol lowering therapies and
      alternative interventions for improving vascular function. With specific
      relevance to the microcirculation, it has been clearly demonstrated that
      evolution of hypercholesterolemia is associated with endothelial cell
      dysfunction, a near-complete abrogation in vascular nitric oxide bioavailability,
      elevated oxidant stress, and the creation of a strongly pro-inflammatory
      condition; symptoms which can culminate in profound impairments/alterations to
      vascular reactivity. Effective interventional treatments can be challenging as
      certain genetic risk factors simply cannot be ignored. However, some
      hypercholesterolemia treatment options that have become widely used, including
      pharmaceutical therapies which can decrease circulating cholesterol by preventing
      either its formation in the liver or its absorption in the intestine, also have
      pleiotropic effects with can directly improve peripheral vascular outcomes. While
      physical activity is known to decrease PVD/CAD risk factors, including obesity,
      psychological stress, impaired glycemic control, and hypertension, this will also
      increase circulating levels of high density lipoprotein and improving both
      cardiac and vascular function. This review will provide an overview of the
      mechanistic consequences of the predominant pharmaceutical interventions and
      chronic exercise to treat hypercholesterolemia through their impacts on chronic
      sub-acute inflammation, oxidative stress, and microvascular structure/function
      relationships.

PMID- 21087506
TI  - Alcohol use among amateur sportsmen in Ireland.
AB  - BACKGROUND: The objective of this study was to establish baseline data on alcohol
      consumption patterns, behaviours and harms among amateur sportsmen in the
      Republic of Ireland. FINDINGS: The study presents findings from the baseline
      survey for a cluster randomised controlled trial to evaluate the effectiveness of
      a community intervention programme to reduce problem alcohol use among a
      representative sample of Gaelic Athletic Association (GAA) clubs in two counties
      in the Republic of Ireland. Self reported alcohol use, prevalence of binge
      drinking, AUDIT scores and alcohol-related harms were assessed in amateur GAA
      sportsmen aged 16 years and over.Nine hundred and sixty (960) players completed
      questionnaires (72% response rate). Mean age was 24.0 years (S.D. 5.2). Of those
      aged 18 years or over, 75% had post-primary education; most (864, 90%) were
      current drinkers and 8.2% were regular smokers. The self-reported average yearly
      alcohol consumption was 12.5 litres. Almost one third (31%) of current drinkers
      reported drinking over the recommended limit of 21 standard drinks per week and
      just over half (54.3%) reported drinking 6 or more standard drinks in a row at
      least once a week (regular binge drinking). Of those who (self) completed the
      Alcohol Use Disorder Identification Test (AUDIT) questionnaire, three-quarters
      (74.7%) had a score of 8 or more; 11.5% had a score of 20 or above warranting
      referral for diagnostic evaluation and treatment. Almost all (87.6%) of the 864
      drinkers reported experiencing at least one harm due to their drinking. These
      alcohol misuse outcomes were higher than those found in a nationally
      representative sample of males of a similar age. There were strong associations
      between regular binge drinking and reporting harms such as being in a fight
      (adjusted odds ratio (OR) 2.02, p < 0.001), missing time from work or college
      (adjusted OR 1.39, p = 0.04) or being in an accident (adjusted OR 1.78, p =
      0.04). CONCLUSIONS: These male amateur sportsmen reported high rates of alcohol
      consumption and alcohol-related harm.

PMID- 21087507
TI  - Effects of human mesenchymal stem cells on ER-positive human breast carcinoma
      cells mediated through ER-SDF-1/CXCR4 crosstalk.
AB  - BACKGROUND: Adult human mesenchymal stem cells (hMSC) have been shown to home to
      sites of carcinoma and affect biological processes, including tumour growth and
      metastasis. Previous findings have been conflicting and a clear understanding of
      the effects of hMSCs on cancer remains to be established. Therefore, we set out
      to investigate the impact of hMSCs on the oestrogen receptor positive, hormone
      dependent breast carcinoma cell line MCF-7. RESULTS: In this study, we show the
      effects of hMSCs on cancer cells are mediated through a secreted factor(s) which
      are enhanced by cancer cell-hMSC contact/communication. In addition to enhanced
      proliferation when in co-culture with hMSCs, MCF-7 cells were found to have
      increased migration potential in vitro. Inhibition of ER signalling by the pure
      anti-oestrogen ICI 182,780 decreased the effect of hMSCs on MCF-7 cell
      proliferation and migration supporting a role for ER signalling in the hMSC/MCF-7
      cell interaction. Additionally, hMSCs have been shown to secrete a wide variety
      of growth factors and chemokines including stromal cell-derived factor-1 (SDF-1).
      This coupled with the knowledge that SDF-1 is an ER-mediated gene linked with
      hormone-independence and metastasis led to the investigation of the SDF-1/CXCR4
      signalling axis in hMSC-MCF-7 cell interaction. Experiments revealed an increase
      in SDF-1 gene expression both in vivo and in vitro when MCF-7 cells were cultured
      with hMSCs. SDF-1 treatment of MCF-7 cells alone increased proliferation to just
      below that seen with hMSC co-culture. Additionally, blocking SDF-1 signalling
      using a CXCR4-specific inhibitor decreased hMSC induced proliferation and
      migration of MCF-7. However, the combined treatment of ICI and AMD3100 reduced
      MCF-7 cell proliferation and migration below control levels, indicating targeting
      both the ER and CXCR4 pathways is effective in decreasing the hMSCs induction of
      MCF-7 cell proliferation and migration. CONCLUSIONS: The sum of these data
      reveals the relationship between tumour microenvironment and tumour growth and
      progression. Better understanding of the mechanisms involved in this tumour
      stroma cell interaction may provide novel targets for the development of
      treatment strategies for oestrogen receptor positive, hormone-independent, and
      endocrine-resistant breast carcinoma.

PMID- 21087509
TI  - Comparative study of unsupervised dimension reduction techniques for the
      visualization of microarray gene expression data.
AB  - BACKGROUND: Visualization of DNA microarray data in two or three dimensional
      spaces is an important exploratory analysis step in order to detect quality
      issues or to generate new hypotheses. Principal Component Analysis (PCA) is a
      widely used linear method to define the mapping between the high-dimensional data
      and its low-dimensional representation. During the last decade, many new
      nonlinear methods for dimension reduction have been proposed, but it is still
      unclear how well these methods capture the underlying structure of microarray
      gene expression data. In this study, we assessed the performance of the PCA
      approach and of six nonlinear dimension reduction methods, namely Kernel PCA,
      Locally Linear Embedding, Isomap, Diffusion Maps, Laplacian Eigenmaps and Maximum
      Variance Unfolding, in terms of visualization of microarray data. RESULTS: A
      systematic benchmark, consisting of Support Vector Machine classification,
      cluster validation and noise evaluations was applied to ten microarray and
      several simulated datasets. Significant differences between PCA and most of the
      nonlinear methods were observed in two and three dimensional target spaces. With
      an increasing number of dimensions and an increasing number of differentially
      expressed genes, all methods showed similar performance. PCA and Diffusion Maps
      responded less sensitive to noise than the other nonlinear methods. CONCLUSIONS:
      Locally Linear Embedding and Isomap showed a superior performance on all
      datasets. In very low-dimensional representations and with few differentially
      expressed genes, these two methods preserve more of the underlying structure of
      the data than PCA, and thus are favorable alternatives for the visualization of
      microarray data.

PMID- 21087508
TI  - MATH5 controls the acquisition of multiple retinal cell fates.
AB  - Math5-null mutation results in the loss of retinal ganglion cells (RGCs) and in a
      concurrent increase of amacrine and cone cells. However, it remains unclear
      whether there is a cell fate switch of Math5-lineage cells in the absence of
      Math5 and whether MATH5 cell-autonomously regulates the differentiation of the
      above retinal neurons. Here, we performed a lineage analysis of Math5-expressing
      cells in developing mouse retinas using a conditional GFP reporter (Z/EG)
      activated by a Math5-Cre knock-in allele. We show that during normal
      retinogenesis, Math5-lineage cells mostly develop into RGCs, horizontal cells,
      cone photoreceptors, rod photoreceptors, and amacrine cells. Interestingly,
      amacrine cells of Math5-lineage cells are predominately of GABAergic,
      cholinergic, and A2 subtypes, indicating that Math5 plays a role in amacrine
      subtype specification. In the absence of Math5, more Math5-lineage cells undergo
      cell fate conversion from RGCs to the above retinal cell subtypes, and
      occasionally to cone-bipolar cells and Muller cells. This change in cell fate
      choices is accompanied by an up-regulation of NEUROD1, RXRgamma and BHLHB5, the
      transcription factors essential for the differentiation of retinal cells other
      than RGCs. Additionally, loss of Math5 causes the failure of early progenitors to
      exit cell cycle and leads to a significant increase of Math5-lineage cells
      remaining in cell cycle. Collectively, these data suggest that Math5 regulates
      the generation of multiple retinal cell types via different mechanisms during
      retinogenesis.

PMID- 21087510
TI  - Difference in gene duplicability may explain the difference in overall structure
      of protein-protein interaction networks among eukaryotes.
AB  - BACKGROUND: A protein-protein interaction network (PIN) was suggested to be a
      disassortative network, in which interactions between high- and low-degree nodes
      are favored while hub-hub interactions are suppressed. It was postulated that a
      disassortative structure minimizes unfavorable cross-talks between different hub
      centric functional modules and was positively selected in evolution. However, by
      re-examining yeast PIN data, several researchers reported that the disassortative
      structure observed in a PIN might be an experimental artifact. Therefore, the
      existence of a disassortative structure and its possible evolutionary mechanism
      remains unclear. RESULTS: In this study, we investigated PINs from the yeast,
      worm, fly, human, and malaria parasite including four different yeast PIN
      datasets. The analyses showed that the yeast, worm, fly, and human PINs are
      disassortative while the malaria parasite PIN is not. By conducting simulation
      studies on the basis of a duplication-divergence model, we demonstrated that a
      preferential duplication of low- and high-degree nodes can generate
      disassortative and non-disassortative networks, respectively. From this
      observation, we hypothesized that the difference in degree dependence on gene
      duplications accounts for the difference in assortativity of PINs among species.
      Comparison of 55 proteomes in eukaryotes revealed that genes with lower degrees
      showed higher gene duplicabilities in the yeast, worm, and fly, while high-degree
      genes tend to have high duplicabilities in the malaria parasite, supporting the
      above hypothesis. CONCLUSIONS: These results suggest that disassortative
      structures observed in PINs are merely a byproduct of preferential duplications
      of low-degree genes, which might be caused by an organism's living environment.

PMID- 21087512
TI  - Small cell carcinoma in ulcerative colitis--new treatment option: a case report.
AB  - BACKGROUND: The most common type of carcinoma associated with ulcerative colitis
      (UC) is adenocarcinoma. We present a case of primary rectal small cell carcinoma
      in a patient with a history of UC. METHODS: A 34-year-old male diagnosed with UC
      for 10 years was not consistent with the usual annual follow-up and presented
      with mucoid-bloody diarrhea. Colonoscopy revealed a rectal mass 2 cm distant from
      the anal verge. The patient underwent a total proctocolectomy with preservation
      of the anal sphincters, construction of an ileal reservoir, anastomosis of the
      reservoir to the anus (J configuration) and protective loop ileostomy. RESULTS:
      Histological examination showed undifferentiated small cell carcinoma.
      CONCLUSIONS: This is the first case of small cell carcinoma in a background of UC
      reported to be treated surgically and the patient and has no recurrence 18 months
      postoperatively.

PMID- 21087511
TI  - Retention of progenitor cell phenotype in otospheres from guinea pig and mouse
      cochlea.
AB  - BACKGROUND: Culturing otospheres from dissociated organ of Corti is an
      appropriate starting point aiming at the development of cell therapy for hair
      cell loss. Although guinea pigs have been widely used as an excellent
      experimental model for studying the biology of the inner ear, the mouse cochlea
      has been more suitable for yielding otospheres in vitro. The aim of this study
      was to compare conditions and outcomes of otosphere suspension cultures from
      dissociated organ of Corti of either mouse or guinea pig at postnatal day three
      (P3), and to evaluate the guinea pig as a potential cochlea donor for preclinical
      cell therapy. METHODS: Organs of Corti were surgically isolated from P3 guinea
      pig or mouse cochlea, dissociated and cultivated under non-adherent conditions.
      Cultures were maintained in serum-free DMEM:F12 medium, supplemented with
      epidermal growth factor (EGF) plus either basic fibroblast growth factor (bFGF)
      or transforming growth factor alpha (TGFalpha). Immunofluorescence assays were
      conducted for phenotype characterization. RESULTS: The TGFalpha group presented a
      number of spheres significantly higher than the bFGF group. Although mouse
      cultures yielded more cells per sphere than guinea pig cultures, sox2 and nestin
      distributed similarly in otosphere cells from both organisms. We present evidence
      that otospheres retain properties of inner ear progenitor cells such as self
      renewal, proliferation, and differentiation into hair cells or supporting cells.
      CONCLUSIONS: Dissociated guinea pig cochlea produced otospheres in vitro,
      expressing sox2 and nestin similarly to mouse otospheres. Our data is supporting
      evidence for the presence of inner ear progenitor cells in the postnatal guinea
      pig. However, there is limited viability for these cells in neonatal guinea pig
      cochlea when compared to the differentiation potential observed for the mouse
      organ of Corti at the same developmental stage.

PMID- 21087513
TI  - Status, challenges and facilitators of consumer involvement in Australian health
      and medical research.
AB  - BACKGROUND: The emergent international practice of involving consumers in health
      research is driven, in part, by the growing share of health research that can
      only be applied in and emerge from knowledge that is shaped by human values and
      societal contexts. This is the first investigation of its kind to identify the
      current prevalence, challenges, enabling factors and range of approaches to
      consumer involvement in health and medical research in Australia. METHODS: A
      nation-wide survey of research funding organisations and organisations that
      conduct research was performed during 2008-2009. RESULTS: Marked variation in
      consumer involvement experience and perceptions exists between research funders
      and researchers. Research funders were over eight times more likely than
      organisations conducting research to involve consumers in identifying research
      needs and prioritising research topics. Across both groups, practical and time
      constraints were reported as key challenges to involving consumers, while
      guidelines on consumer involvement and evidence of effect were the most important
      potential enablers. More than a third of research organisations indicated that
      when consumer involvement was a condition of research funding, it was an
      important facilitator of involvement. CONCLUSION: It is no longer simply enough
      to keep society informed of important scientific breakthroughs. If Australian
      health research is to take into account important social contexts and
      consequences, it must involve consumers. A set of minimum consumer involvement
      standards and associated guidelines, that are agreed and routinely adopted, could
      ensure that consumers and the Australian community they represent, are given an
      opportunity to shed light on experiences and local circumstance, and express
      views and concerns relevant to health research.

PMID- 21087514
TI  - Grammatical evolution decision trees for detecting gene-gene interactions.
AB  - BACKGROUND: A fundamental goal of human genetics is the discovery of
      polymorphisms that predict common, complex diseases. It is hypothesized that
      complex diseases are due to a myriad of factors including environmental exposures
      and complex genetic risk models, including gene-gene interactions. Such epistatic
      models present an important analytical challenge, requiring that methods perform
      not only statistical modeling, but also variable selection to generate testable
      genetic model hypotheses. This challenge is amplified by recent advances in
      genotyping technology, as the number of potential predictor variables is rapidly
      increasing. METHODS: Decision trees are a highly successful, easily interpretable
      data-mining method that are typically optimized with a hierarchical model
      building approach, which limits their potential to identify interacting effects.
      To overcome this limitation, we utilize evolutionary computation, specifically
      grammatical evolution, to build decision trees to detect and model gene-gene
      interactions. In the current study, we introduce the Grammatical Evolution
      Decision Trees (GEDT) method and software and evaluate this approach on simulated
      data representing gene-gene interaction models of a range of effect sizes. We
      compare the performance of the method to a traditional decision tree algorithm
      and a random search approach and demonstrate the improved performance of the
      method to detect purely epistatic interactions. RESULTS: The results of our
      simulations demonstrate that GEDT has high power to detect even very moderate
      genetic risk models. GEDT has high power to detect interactions with and without
      main effects. CONCLUSIONS: GEDT, while still in its initial stages of
      development, is a promising new approach for identifying gene-gene interactions
      in genetic association studies.

PMID- 21087515
TI  - Multiple phenotypic changes in mice after knockout of the B3gnt5 gene, encoding
      Lc3 synthase--a key enzyme in lacto-neolacto ganglioside synthesis.
AB  - BACKGROUND: Ganglioside biosynthesis occurs through a multi-enzymatic pathway
      which at the lactosylceramide step is branched into several biosynthetic series.
      Lc3 synthase utilizes a variety of galactose-terminated glycolipids as acceptors
      by establishing a glycosidic bond in the beta-1,3-linkage to GlcNaAc to extend
      the lacto- and neolacto-series gangliosides. In order to examine the lacto-series
      ganglioside functions in mice, we used gene knockout technology to generate Lc3
      synthase gene B3gnt5-deficient mice by two different strategies and compared the
      phenotypes of the two null mouse groups with each other and with their wild-type
      counterparts. RESULTS: B3gnt5 gene knockout mutant mice appeared normal in the
      embryonic stage and, if they survived delivery, remained normal during early
      life. However, about 9% developed early-stage growth retardation, 11% died
      postnatally in less than 2 months, and adults tended to die in 5-15 months,
      demonstrating splenomegaly and notably enlarged lymph nodes. Without lacto
      neolacto series gangliosides, both homozygous and heterozygous mice gradually
      displayed fur loss or obesity, and breeding mice demonstrated reproductive
      defects. Furthermore, B3gnt5 gene knockout disrupted the functional integrity of
      B cells, as manifested by a decrease in B-cell numbers in the spleen, germinal
      center disappearance, and less efficiency to proliferate in hybridoma fusion.
      CONCLUSIONS: These novel results demonstrate unequivocally that lacto-neolacto
      series gangliosides are essential to multiple physiological functions, especially
      the control of reproductive output, and spleen B-cell abnormality. We also report
      the generation of anti-IgG response against the lacto-series gangliosides 3'
      isoLM1 and 3',6'-isoLD1.

PMID- 21087516
TI  - Developing a performance measurement framework and indicators for community
      health service facilities in urban China.
AB  - BACKGROUND: China has had no effective and systematic information system to
      provide guidance for strengthening PHC (Primary Health Care) or account to
      citizens on progress. We report on the development of the China results-based
      Logic Model for Community Health Facilities and Stations (CHS) and a set of
      relevant PHC indicators intended to measure CHS priorities. METHODS: We adapted
      the PHC Results Based Logic Model developed in Canada and current work conducted
      in the community health system in China to create the China CHS Logic Model
      framework. We used a staged approach by first constructing the framework and
      indicators and then validating their content through an interactive process
      involving policy analysis, critical review of relevant literature and multiple
      stakeholder consultation. RESULTS: The China CHS Logic Model includes inputs,
      activities, outputs and outcomes with a total of 287 detailed performance
      indicators. In these indicators, 31 indicators measure inputs, 64 measure
      activities, 105 measure outputs, and 87 measure immediate (n = 65), intermediate
      (n = 15), or final (n = 7) outcomes. CONCLUSION: A Logic Model framework can be
      useful in planning, implementation, analysis and evaluation of PHC at a system
      and service level. The development and content validation of the China CHS Logic
      Model and subsequent indicators provides a means for stronger accountability and
      a clearer sense of overall direction and purpose needed to renew and strengthen
      the PHC system in China. Moreover, this work will be useful in moving towards
      developing a PHC information system and performance measurement across districts
      in urban China, and guiding the pursuit of quality in PHC.

PMID- 21087518
TI  - Association analysis of PRNP gene region with chronic wasting disease in Rocky
      Mountain elk.
AB  - BACKGROUND: Chronic wasting disease (CWD) is a transmissible spongiform
      encephalopathy (TSE) of cervids including white-tailed (Odocoileus virginianus)
      and mule deer (Odocoileus hemionus), Rocky Mountain elk (Cervus elaphus nelsoni),
      and moose (Alces alces). A leucine variant at position 132 (132L) in prion
      protein of Rocky Mountain elk confers a long incubation time with CWD, but not
      complete resistance. However, variants in regulatory regions outside the open
      reading frame of PRNP have been associated with varying degrees of susceptibility
      to prion disease in other species, and some variants have been observed in
      similar regions of Rocky Mountain elk PRNP. Thus, additional genetic variants
      might provide increased protection, either alone or in combination with 132L.
      FINDINGS: This study provided genomic sequence of all exons for PRNP of Rocky
      Mountain elk. Many functional sites in and around the PRNP gene region were
      sequenced, and this report approximately doubled (to 75) the number of known
      variants in this region. A haplotype-tagging approach was used to reduce the
      number of genetic variants required to survey this variation in the PRNP gene
      region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies
      over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited
      genetic diversity in the PRNP gene region. CONCLUSIONS: The presence of 132L cut
      odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar
      to a previous report. However after accounting for 132L, no association with CWD
      was found for any additional variants in the PRNP region (P > 0.05).

PMID- 21087517
TI  - Heme and blood-feeding parasites: friends or foes?
AB  - Hemoparasites, like malaria and schistosomes, are constantly faced with the
      challenges of storing and detoxifying large quantities of heme, released from
      their catabolism of host erythrocytes. Heme is an essential prosthetic group that
      forms the reactive core of numerous hemoproteins with diverse biological
      functions. However, due to its reactive nature, it is also a potentially toxic
      molecule. Thus, the acquisition and detoxification of heme is likely to be
      paramount for the survival and establishment of parasitism. Understanding the
      underlying mechanism involved in this interaction could possibly provide
      potential novel targets for drug and vaccine development, and disease treatment.
      However, there remains a wide gap in our understanding of these mechanisms. This
      review summarizes the biological importance of heme for hemoparasite, and the
      adaptations utilized in its sequestration and detoxification.

PMID- 21087519
TI  - A hereditary spastic paraplegia mutation in kinesin-1A/KIF5A disrupts
      neurofilament transport.
AB  - BACKGROUND: Hereditary spastic paraplegias are a group of neurological disorders
      characterized by progressive distal degeneration of the longest ascending and
      descending axons in the spinal cord, leading to lower limb spasticity and
      weakness. One of the dominantly inherited forms of this disease (spastic gait
      type 10, or SPG10) is caused by point mutations in kinesin-1A (also known as
      KIF5A), which is thought to be an anterograde motor for neurofilaments. RESULTS:
      We investigated the effect of an SPG10 mutation in kinesin-1A (N256S-kinesin-1A)
      on neurofilament transport in cultured mouse cortical neurons using live-cell
      fluorescent imaging. N256S-kinesin-1A decreased both anterograde and retrograde
      neurofilament transport flux by decreasing the frequency of anterograde and
      retrograde movements. Anterograde velocity was not affected, whereas retrograde
      velocity actually increased. CONCLUSIONS: These data reveal subtle complexities
      to the functional interdependence of the anterograde and retrograde neurofilament
      motors and they also raise the possibility that anterograde and retrograde
      neurofilament transport may be disrupted in patients with SPG10.

PMID- 21087520
TI  - Determinants of leptospirosis in Sri Lanka: study protocol.
AB  - BACKGROUND: Leptospirosis is becoming a major public health threat in Sri Lanka
      as well as in other countries. We designed a case control study to determine the
      factors associated with local transmission of leptospirosis in Sri Lanka, in
      order to identify major modifiable determinants of leptospirosis. The purpose of
      this paper is to describe the study protocol in detail prior to the publishing of
      the study results, so that the readership will be able to understand and
      interpret the study results effectively. METHODS: A hospital based partially
      matched case control design is proposed. The study will be conducted in three
      selected leptospirosis endemic districts in central Sri Lanka. Case selection
      will include screening all acute fever patients admitted to selected wards to
      select probable cases of leptospirosis and case confirmation using an array of
      standard laboratory criteria. Age and sex matched group of acute fever patients
      with other confirmed diagnosis will be used as controls. Case to control ratio
      will be 1:2. A minimum sample of 144 cases is required to detect 20% exposure
      with 95% two sided confidence level and 80% power. A pre tested interviewer
      administered structured questionnaire will be used to collect data from
      participants. Variables included in the proposed study will be evaluated using
      conceptual hierarch of variables in three levels; Exposure variables as proximal;
      reservoir and environmental variables as intermediate; socio-demographic
      variables as distal. This conceptual hierarch hypothesised that the distal and
      intermediate variables are mediated through the proximal variables but not
      directly. A logistic regression model will be used to analyse the probable
      determinants of leptospirosis. This model will evaluate the effect of same level
      and upper level variables on the outcome leptospirosis, using three blocks.
      DISCUSSION: The present national control programme of leptospirosis is hampered
      by lack of baseline data on leptospirosis disease transmission. The present study
      will be able to provide these essential information for formulation of better
      control strategies.

PMID- 21087522
TI  - Efficacy of postural techniques assessed by videofluoroscopy for myasthenia
      gravis with dysphagia as the presenting symptom: a case report.
AB  - INTRODUCTION: Oropharyngeal weakness leading to dysphagia is rarely the
      presenting symptom of myasthenia gravis, but it can be a significant source of
      morbidity and mortality. The earliest possible diagnosis of myasthenia gravis
      should be made for better management of this cause of treatable dysphagia. A
      detailed evaluation of swallowing by videofluoroscopy can assist in making an
      accurate diagnosis and in individualizing appropriate diet compensatory
      techniques. CASE PRESENTATION: We present the case of a 57-year-old Taiwanese man
      with dysphagia as the presenting symptom of myasthenia gravis, and evaluate the
      pathological findings of swallowing and effectiveness of compensatory postural
      techniques for dysphagia using videofluoroscopy. CONCLUSIONS: Videofluoroscopy is
      a valuable technique for evaluating myasthenia gravis dysphagia, because it
      allows swallowing interventions to be precisely individualized in accordance with
      the results obtained.

PMID- 21087521
TI  - Development of loop-mediated isothermal amplification (LAMP) assays for rapid
      detection of Ehrlichia ruminantium.
AB  - BACKGROUND: The rickettsial bacterium Ehrlichia ruminantium is the causative
      agent of heartwater, a potential zoonotic disease of ruminants transmitted by
      ticks of the genus Amblyomma. The disease is distributed in nearly all of sub
      Saharan Africa and some islands of the Caribbean, from where it threatens the
      American mainland. This report describes the development of two different loop
      mediated isothermal amplification (LAMP) assays for sensitive and specific
      detection of E. ruminantium. RESULTS: Two sets of LAMP primers were designed from
      the pCS20 and sodB genes. The detection limits for each assay were 10 copies for
      pCS20 and 5 copies for sodB, which is at least 10 times higher than that of the
      conventional pCS20 PCR assay. DNA amplification was completed within 60 min. The
      assays detected 16 different isolates of E. ruminantium from geographically
      distinct countries as well as two attenuated vaccine isolates. No cross-reaction
      was observed with genetically related Rickettsiales, including zoonotic Ehrlichia
      species from the USA. LAMP detected more positive samples than conventional PCR
      but less than real-time PCR, when tested with field samples collected in sub
      Saharan countries. CONCLUSIONS: Due to its simplicity and specificity, LAMP has
      the potential for use in resource-poor settings and also for active screening of
      E. ruminantium in both heartwater-endemic areas and regions that are at risk of
      contracting the disease.

PMID- 21087523
TI  - Exploring the molecular mechanisms underlying the potentiation of exogenous
      growth hormone on alcohol-induced fatty liver diseases in mice.
AB  - BACKGROUND: Growth hormone (GH) is an essential regulator of intrahepatic lipid
      metabolism by activating multiple complex hepatic signaling cascades. Here, we
      examined whether chronic exogenous GH administration (via gene therapy) could
      ameliorate liver steatosis in animal models of alcoholic fatty liver disease
      (AFLD) and explored the underlying molecular mechanisms. METHODS: Male C57BL/6J
      mice were fed either an alcohol or a control liquid diet with or without GH
      therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress
      markers, and serum high molecular weight (HMW) adiponectin were measured.
      Quantitative real-time PCR and western blotting were also conducted to determine
      the underlying molecular mechanism. RESULTS: Serum HMW adiponectin levels were
      significantly higher in the GH1-treated control group than in the control group
      (3.98 +/- 0.71 MUg/mL vs. 3.07 +/- 0.55 MUg/mL; P < 0.001). GH1 therapy reversed
      HMW adiponectin levels to the normal levels in the alcohol-fed group. Alcohol
      feeding significantly reduced hepatic adipoR2 mRNA expression compared with that
      in the control group (0.71 +/- 0.17 vs. 1.03 +/- 0.19; P < 0.001), which was
      reversed by GH therapy. GH1 therapy also significantly increased the relative
      mRNA (1.98 +/- 0.15 vs. 0.98 +/- 0.15) and protein levels of SIRT1 (2.18 +/- 0.37
      vs. 0.99 +/- 0.17) in the alcohol-fed group compared with those in the control
      group (both, P < 0.001). The alcohol diet decreased the phosphorylated and total
      protein levels of hepatic AMP-activated kinase-alpha (AMPKalpha) (phosphorylated
      protein: 0.40 +/- 0.14 vs. 1.00 +/- 0.12; total protein: 0.32 +/- 0.12 vs. 1.00
      +/- 0.14; both, P < 0.001) and peroxisome proliferator activated receptor-alpha
      (PPARalpha) (phosphorylated protein: 0.30 +/- 0.09 vs. 1.00 +/- 0.09; total
      protein: 0.27 +/- 0.10 vs. 1.00 +/- 0.13; both, P < 0.001), which were restored
      by GH1 therapy. GH therapy also decreased the severity of fatty liver in alcohol
      fed mice. CONCLUSIONS: GH therapy had positive effects on AFLD and may offer a
      promising approach to prevent or treat AFLD. These beneficial effects of GH on
      AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK
      and PPARalpha-AMPK signaling systems.

PMID- 21087524
TI  - Prescriber and staff perceptions of an electronic prescribing system in primary
      care: a qualitative assessment.
AB  - BACKGROUND: The United States (US) Health Information Technology for Economic and
      Clinical Health Act of 2009 has spurred adoption of electronic health records.
      The corresponding meaningful use criteria proposed by the Centers for Medicare
      and Medicaid Services mandates use of computerized provider order entry (CPOE)
      systems. Yet, adoption in the US and other Western countries is low and
      descriptions of successful implementations are primarily from the inpatient
      setting; less frequently the ambulatory setting. We describe prescriber and staff
      perceptions of implementation of a CPOE system for medications (electronic- or e
      prescribing system) in the ambulatory setting. METHODS: Using a cross-sectional
      study design, we conducted eight focus groups at three primary care sites in an
      independent medical group. Each site represented a unique stage of e-prescribing
      implementation - pre/transition/post. We used a theoretically based, semi
      structured questionnaire to elicit physician (n = 17) and staff (n = 53)
      perceptions of implementation of the e-prescribing system. We conducted a
      thematic analysis of focus group discussions using formal qualitative analytic
      techniques (i.e. deductive framework and grounded theory). Two coders
      independently coded to theoretical saturation and resolved discrepancies through
      discussions. RESULTS: Ten themes emerged that describe perceptions of e
      prescribing implementation: 1) improved availability of clinical information
      resulted in prescribing efficiencies and more coordinated care; 2) improved
      documentation resulted in safer care; 3) efficiencies were gained by using fewer
      paper charts; 4) organizational support facilitated adoption; 5) transition
      required time; resulted in workload shift to staff; 6) hardware configurations
      and network stability were important in facilitating workflow; 7) e-prescribing
      was time-neutral or time-saving; 8) changes in patient interactions enhanced
      patient care but required education; 9) pharmacy communications were enhanced but
      required education; 10) positive attitudes facilitated adoption. CONCLUSIONS:
      Prescribers and staff worked through the transition to successfully adopt e
      prescribing, and noted the benefits. Overall impressions were favorable. No one
      wished to return to paper-based prescribing.

PMID- 21087525
TI  - Scale-adaptive surface modeling of vascular structures.
AB  - BACKGROUND: The effective geometric modeling of vascular structures is crucial
      for diagnosis, therapy planning and medical education. These applications require
      good balance with respect to surface smoothness, surface accuracy, triangle
      quality and surface size. METHODS: Our method first extracts the vascular
      boundary voxels from the segmentation result, and utilizes these voxels to build
      a three-dimensional (3D) point cloud whose normal vectors are estimated via
      covariance analysis. Then a 3D implicit indicator function is computed from the
      oriented 3D point cloud by solving a Poisson equation. Finally the vessel surface
      is generated by a proposed adaptive polygonization algorithm for explicit 3D
      visualization. RESULTS: Experiments carried out on several typical vascular
      structures demonstrate that the presented method yields both a smooth
      morphologically correct and a topologically preserved two-manifold surface, which
      is scale-adaptive to the local curvature of the surface. Furthermore, the
      presented method produces fewer and better-shaped triangles with satisfactory
      surface quality and accuracy. CONCLUSIONS: Compared to other state-of-the-art
      approaches, our method reaches good balance in terms of smoothness, accuracy,
      triangle quality and surface size. The vessel surfaces produced by our method are
      suitable for applications such as computational fluid dynamics simulations and
      real-time virtual interventional surgery.

PMID- 21087526
TI  - The nature and combination of subunits used in epitope-based Schistosoma
      japonicum vaccine formulations affect their efficacy.
AB  - BACKGROUND: Schistosomiasis remains a major public health problem in endemic
      countries and is caused by infections with any one of three primary schistosome
      species. Although there are no vaccines available to date, this strategy appears
      feasible since natural immunity develops in individuals suffering from repeated
      infection during a lifetime. Since vaccinations resulting in both Th1- and Th2
      type responses have been shown to contribute to protective immunity, a vaccine
      formulation with the capacity for stimulating multiple arms of the immune
      response will likely be the most effective. Previously we developed partially
      protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV)
      (T3-PDDV and B3-PDDV, respectively) capable of eliciting immune responses against
      the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6) and a 62 kDa
      fragment of myosin (Sj62), respectively. RESULTS: In this study, we developed
      PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and
      Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated
      vaccine potential in vivo. Results showed that mice immunized with a single
      epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice
      immunized with either the T3- or B3- single-epitope PDDV formulation were
      partially protected against infection. However, mice immunized with a
      multicomponent (3 PDDV components) formulation elicited variable immune responses
      that were less immunoprotective than single-epitope PDDV formulations.
      CONCLUSIONS: Our data show that combining these different antigens did not result
      in a more effective vaccine formulation when compared to each component
      administered individually, and further suggest that immune interference resulting
      from immunizations with antigenically distinct vaccine targets may be an
      important consideration in the development of multicomponent vaccine
      preparations.

PMID- 21087527
TI  - HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice.
AB  - Several approaches have been explored to eradicate HIV; however, a multigene
      vaccine appears to be the best option, given their proven potential to elicit
      broad, effective responses in animal models. The Pr55Gag protein is an excellent
      vaccine candidate in its own right, given that it can assemble into large,
      enveloped, virus-like particles (VLPs) which are highly immunogenic, and can
      moreover be used as a scaffold for the presentation of other large non-structural
      HIV antigens. In this study, we evaluated the potential of two novel chimaeric
      HIV-1 Pr55Gag-based VLP constructs - C-terminal fusions with reverse
      transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN
      respectively - to enhance a cellular response in mice when used as boost
      components in two types of heterologous prime-boost vaccine strategies. A vaccine
      regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced
      strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The
      enhanced cellular responses induced by the DNA prime-VLP boost were two- to three
      fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN
      VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP
      vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The
      results demonstrate the promising potential of these chimaeric VLPs as vaccine
      candidates against HIV-1.

PMID- 21087528
TI  - p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and
      enhances chemosensitivity to cisplatin in lung carcinoma cell.
AB  - BACKGROUND: Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and
      are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a
      cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in
      many in vitro cellular models. RNA activation (RNAa) is a transcriptional
      activation phenomena guided by double-strand RNA (dsRNA) targeting promoter
      region of target gene. METHODS: In this study, we explored the effect of up
      regulation of p21 gene expression on drug-resistance in A549 non-small-cell lung
      carcinoma cells by transfecting the dsRNA targeting the promoter region of p21
      into A549 cells. RESULTS: Enhanced p21 expression was observed in A549 cells
      after transfection of dsRNA, which was correlated with a significant growth
      inhibition and enhancement of chemosensitivity to cisplatin in A549 cells in
      vitro. Moreover, in vivo experiment showed that saRNA targeting the promoter
      region of p21 could significantly inhibit A549 xenograft tumor growth.
      CONCLUSIONS: These results indicate that p21 plays a role in lung cancer drug
      resistance process. In addition, this study also provides evidence for the usage
      of saRNA as a therapeutic option for up-regulating lower-expression genes in lung
      cancer.

PMID- 21087529
TI  - The reported thoracic injuries in Homer's Iliad.
AB  - Homer's Iliad is considered to be a prominent and representative work of the
      tradition of the ancient Greek epic poetry. In this poem Homer presents the
      battles which took place during the last year of the 10-year lasting Trojan War
      between Achaeans and Trojans. We wanted to examine the chest wounds, especially
      those which are described in detail, according to their localization, severity
      and mortality. Finally, there are reported 54 consecutive thoracic injuries in
      the Iliad. The mostly used weapons were the spear (63%), the stones (7.4%), the
      arrow (5.5%) and the sword (5.5%). We divided the injuries according to their
      severity in mild (those which did not cause serious injury to the victim), medium
      (those which cause the victim to abandon the battlefield), and severe (those
      which cause death of the victim). According to this classification, the reported
      injuries were mild in 11.11%, medium in 18.52%, and severe in the last 70.37% of
      the reported cases. In other words, 89% of the injuries belong to the medium or
      severe category of thoracic injury. As far as the mortality of the injuries is
      concerned, 38 out of 54 thoracic injuries include death, which makes the
      mortality percentage reach 70.37%. Concerning the "allocation of the roles", the
      Achaean were in 68% perpetrators and the Trojans in only 32%. In terms of
      gravity, out of 38 mortal injuries 30 involve a Trojan (78.95%) and the remaining
      8 an Achaean (21.05%). The excellent and detailed description of the injuries by
      Homer, as well as of the symptoms, may reveal a man with knowledge of anatomy and
      medicine who cared for the injured warriors in the battlefield.

PMID- 21087531
TI  - African trypanosomiasis: new insights for disease control. Preface.

PMID- 21087530
TI  - Comparison of the collagen haemostat Sangustop(r) versus a carrier-bound fibrin
      sealant during liver resection; ESSCALIVER-Study.
AB  - BACKGROUND: Haemostasis in liver surgery remains a challenge despite improved
      resection techniques. Oozing from blood vessels too small to be ligated
      necessitate a treatment with haemostats in order to prevent complications
      attributed to bleeding. There is good evidence from randomised trials for the
      efficacy of fibrin sealants, on their own or in combination with a carrier
      material. A new haemostatic device is Sangustop(r). It is a collagen based
      material without any coagulation factors. Pre-clinical data for Sangustop(r)
      showed superior haemostatic effect. This present study aims to show that in the
      clinical situation Sangustop(r) is not inferior to a carrier-bound fibrin sealant
      (Tachosil(r)) as a haemostatic treatment in hepatic resection. METHODS/DESIGN:
      This is a multi-centre, patient-blinded, intra-operatively randomised controlled
      trial. A total of 126 patients planned for an elective liver resection will be
      enrolled in eight surgical centres. The primary objective of this study is to
      show the non-inferiority of Sangustop(r) versus a carrier-bound fibrin sealant
      (Tachosil(r)) in achieving haemostasis after hepatic resection. The surgical
      intervention is standardised with regard to devices and techniques used for
      resection and primary haemostasis. Patients will be followed-up for three months
      for complications and adverse events. DISCUSSION: This randomised controlled
      trial (ESSCALIVER) aims to compare the new collagen haemostat Sangustop(r) with a
      carrier-bound fibrin sealant which can be seen as a "gold standard" in hepatic
      and other visceral organ surgery. If non-inferiority is shown other criteria than
      the haemostatic efficacy (e.g. costs, adverse events rate) may be considered for
      the choice of the most appropriate treatment. TRIAL REGISTRATION: NCT00918619.

PMID- 21087532
TI  - Modulation of innate immunity by African trypanosomes.
AB  - The experimental studies of Brucei group trypanosomes presented here demonstrate
      that the balance of host and parasite factors, especially IFN-gamma GPI-sVSG
      respectively, and the timing of cellular exposure to them, dictate the
      predominant MP and DC activation profiles present at any given time during
      infection and within specific tissues. The timing of changes in innate immune
      cell functions following infection consistently support the conclusion that the
      key events controlling host resistance occur within a short time following
      initial exposure to the parasite GPI substituents. Once the changes in MP and DC
      activities are initiated, there appears little that the host can do to reverse
      these changes and alter the final outcome of these regulatory events. Instead,
      despite the availability of multiple innate and adaptive immune mechanisms that
      can control parasites, there is an inability to control trypanosome numbers
      sufficiently to prevent the emergence and establishment of virulent trypanosomes
      that eventually kill the host. Overall it appears that trypanosomes have
      carefully orchestrated the host innate and adaptive immune response so that
      parasite survival and transmission, and alterations of host immunity, are to its
      ultimate benefit.

PMID- 21087533
TI  - Phylogeny and taxonomy of Potamotrygonocotyle Mayes, Brooks & Thorson, 1981
      (Monogenoidea: Monocotylidae) with a description of four new species.
AB  - The marine-derived stingrays of Potamotrygonidae, endemic to South American river
      systems, host an interesting parasite fauna equally related to marine lineages.
      Among those lineages, the diversity and phylogenetic relationships within
      Potamotrygonocotyle - a monocotylid monogenoidean specific to potamotrygonids -
      are poorly known, since 9 of 10 species attributed to this genus have been
      described in the past 3 years. Here, we readdress the diversity of
      Potamotrygonocotyle after examining the gills of 436 potamotrygonid individuals
      representing 12 described and 14 potentially undescribed species of freshwater
      stingrays from 19 major river systems of South America (i.e. sub-basins). We
      recognized 12 valid species within the parasite genus, of which four are
      described in this study. Our taxonomic decisions were based on the phylogenetic
      analysis of 14 ingroup terminal taxa and 12 morphological characters, which
      resulted in the following hypothesis of sister-group relationships: ((P.
      dromedarius, P. tatianae sp. nov.), (P. rionegrense, P. auriculocotyle sp. nov.,
      ((P. quadracotyle, P. umbella), (P. septemcotyle sp. nov., (P. chisholmae, P.
      uruguayense)), (P. tsalickisi, P. eurypotamoxenus, P. rarum, (P. tocantinsense
      sp. nov., P. aramasae))))). According to our hypothesis, the absence of
      autapomorphic features for some nominal species, and the re-evaluation of
      morphological variation among populations, led us to consider P. eurypotamoxenus
      and P. uruguayense as junior synonymys of P. tsalicksi and P. chisholmae,
      respectively. Finally, we address the importance of biogeographic and host
      representation, in order to fully understand the patterns of morphological
      variation and host specificity within this group. We found that hypotheses of
      species delimitation depend greatly on efforts to sample specimens throughout its
      distributional range and that host specificity within this genus varies
      dramatically among lineages.

PMID- 21087534
TI  - Heterorhabditis atacamensis n. sp. (Nematoda: Heterorhabditidae), a new
      entomopathogenic nematode from the Atacama Desert, Chile.
AB  - A new Heterorhabditis species of entomopathogenic nematode was isolated from soil
      of the Atacama Desert in Chile. The new species is characterized by morphometrics
      of the infective juvenile (IJ) with length (L) = 611 (578-666) MUm, head to
      excretory pore length (EP) = 115 (101-126) MUm, tail = 69 (62-79) MUm long,
      (EP/tail) * 100 (E%) = 165 (149-182) and L/maximum body diameter (ratio a) = 28
      (25-31). The male has spicules 45 (40-49) MUm long, gubernaculum 20 (17-22) MUm
      long and (spicule length/anal body diameter) * 100 (SW%) = 205 (179-249). The
      hermaphroditic adult has shallow cuticular folds immediately anterior and
      posterior to the vulva, a slight post-anal swelling and a finely rounded tail
      terminus. Morphologically, H. atacamensis n. sp. resembles H. safricana, H.
      marelatus, H. downesi and H. amazonensis, but can be distinguished by characters
      of adult and IJ stages. In particular, for adult males, H. atacamensis n. sp.
      differs from H. amazonensis by the number and orientation of the genital papillae
      and from H. downesi by the position of the excretory pore; by the shape of the
      female tail terminus from H. downesi and by the position of the IJ hemizonid from
      H. marelatus. Heterorhabditis atacamensis n. sp. is further characterized by
      internal transcribed spacer (ITS) and D2D3 rDNA sequences, the closest species,
      H. safricana, being separated by 13 bp across 730 bp of the ITS (incorporating
      ITS1 (partial sequence), 5.8S (complete sequence), ITS2 (complete sequence)) and
      5 bp across 592 bp of the partial 28S (incorporating D2D3) sequence. The
      morphological and molecular data confirm that H. atacamensis n. sp. is a valid
      species.

PMID- 21087535
TI  - Retrospective cohort study of an outbreak of cryptosporidiosis caused by a rare
      Cryptosporidium parvum subgenotype.
AB  - The occurrence of a gastrointestinal illness among a class of 96 undergraduate
      veterinary students in New Zealand prompted laboratory and questionnaire-based
      investigations. Cryptosporidium parvum was the only enteropathogen identified in
      4/7 faecal specimens analysed. The C. parvum isolates carried a rare IIa GP60
      allele, indicating a point-source outbreak. The infection source could not be
      microbiologically traced, but the investigation suggested contact with calves
      during a practical class as the most likely exposure. A total of 25/80
      respondents to a questionnaire were defined as cases using a clinical case
      definition (31% attack rate). The inferred median incubation period was 5 days
      (range 0-11 days), and the median illness duration was 5-6 days (range 2-23
      days), corroborating previous observations in experimental cryptosporidiosis.
      Disease was self-limiting, characterized by abdominal discomfort, diarrhoea, and
      in some cases, vomiting. Originating from a rural area and having had previously
      handled ruminants were associated with a significant risk reduction in males. All
      the three students who reported chronic use of steroid inhalers for treatment of
      asthma were cases. This case highlighted, once again, the potential hazard for
      explosive outbreaks of cryptosporidiosis.

PMID- 21087536
TI  - Perioperative antibiotic prophylaxis: improved compliance and impact on infection
      rates.
AB  - The aims of this study were to determine adherence to the perioperative
      antibiotic prophylaxis (PAP) protocol used at a large Italian teaching hospital
      during a 6-year period, to assess the variables associated with inappropriate
      administration, and to measure the impact on surgical site infection (SSI) rates.
      There were 28 621 patients surveyed of which 74.6% received PAP. An improvement
      in adherence to the PAP protocol was registered for 58.8% of patients.
      Significant risk factors were an American Society of Anesthesiologists (ASA)
      score >= 2 [odds ratios (OR) from 1.28 (95% confidence interval (CI) 1.19-1.37)
      to 1.87 (95% CI 1.43-2.44)], prolonged duration of surgery (OR 1.68, 95% CI 1.56
      1.82) and urgent surgery (OR 2.16, 95% CI 1.96-2.37). During the study period, a
      significant reduction in SSIs rates was detected. We concluded that the global
      reduction of inadequate PAP administration signifies the efficacy of a
      multidisciplinary quality improvement initiative on antimicrobial utilization,
      and this is supported by the observed reduction of the SSI rate.

PMID- 21087537
TI  - Assessment of the underestimation of childhood diarrhoeal disease burden in
      Israel.
AB  - We determined the extent by which mandatory reporting on isolates of Shigella and
      Salmonella underestimates the burden of diarrhoeal diseases in individuals aged
      <17 years in Israel and examined paediatricians' knowledge, attitudes and
      practices related to patient visits with diarrhoeal diseases. Sources of data
      were a nationwide population-based telephone survey for presence of diarrhoeal
      diseases, Maccabi Healthcare Services databases and a mail survey among its
      paediatricians. Monte Carlo simulation and rate estimates for all stages, from
      visit to physician to reporting on a culture-confirmed case of shigellosis or
      salmonellosis, were used to determine the underestimation factor. Of 1492
      children, 5.7% reported a diarrhoeal episode during the 2 weeks prior to
      interview. The rate of visiting a physician with and without fever was 86% and
      16%, respectively. A stool culture was performed for around 20% of patients and
      the isolation rates were 7.1% for Shigella and 2.1% for Salmonella.
      Paediatricians (n=214) ranked very young age of patient and the complaint 'bloody
      diarrhoea' as the most important determinants. We estimated that one reported
      isolate of Shigella or Salmonella represented 152 diarrhoeal episodes of all
      aetiologies. This estimate is important for further assessments of the true
      burden of diarrhoeal diseases.

PMID- 21087538
TI  - Classification algorithms to improve the accuracy of identifying patients
      hospitalized with community-acquired pneumonia using administrative data.
AB  - In epidemiological studies of community-acquired pneumonia (CAP) that utilize
      administrative data, cases are typically defined by the presence of a pneumonia
      hospital discharge diagnosis code. However, not all such hospitalizations
      represent true CAP cases. We identified 3991 hospitalizations during 1997-2005 in
      a managed care organization, and validated them as CAP or not by reviewing
      medical records. To improve the accuracy of CAP identification, classification
      algorithms that incorporated additional administrative information associated
      with the hospitalization were developed using the classification and regression
      tree analysis. We found that a pneumonia code designated as the primary discharge
      diagnosis and duration of hospital stay improved the classification of CAP
      hospitalizations. Compared to the commonly used method that is based on the
      presence of a primary discharge diagnosis code of pneumonia alone, these
      algorithms had higher sensitivity (81-98%) and positive predictive values (82
      84%) with only modest decreases in specificity (48-82%) and negative predictive
      values (75-90%).

PMID- 21087539
TI  - Estimating time to onset of swine influenza symptoms after initial novel A(H1N1v)
      viral infection.
AB  - Characterization of the incubation time from infection to onset is important for
      understanding the natural history of infectious diseases. Attempts to estimate
      the incubation time distribution for novel A(H1N1v) have been, up to now, based
      on limited data or peculiar samples. We characterized this distribution for a
      generic group of symptomatic cases using laboratory-confirmed swine influenza
      case-information. Estimates of the incubation distribution for the pandemic
      influenza were derived through parametric time-to-event analyses of data on onset
      of symptoms and exposure dates, accounting for interval censoring. We estimated a
      mean of about 1.6-1.7 days with a standard deviation of 2 days for the incubation
      time distribution in those who became symptomatic after infection with the
      A(H1N1v) virus strain. Separate analyses for the <15 years and >= 15 years age
      groups showed a significant (P<0.02) difference with a longer mean incubation
      time in the older age group.

PMID- 21087540
TI  - Hospitalization rates associated with hepatitis B and HIV co-infection, age and
      sex in a population-based cohort of people diagnosed with hepatitis C.
AB  - To determine the extent age, sex and co-infection affect morbidity in people
      infected with hepatitis C virus (HCV), we performed a population-based study
      linking HCV notifications in New South Wales, Australia with their hospital (July
      2000 to June 2006), hepatitis B virus (HBV) and HIV notification, and death
      records. Poisson models were used to calculate hospitalization rate ratios (RRs)
      for all-cause, illicit drug and liver-related admissions. Co-infection RRs were
      used to estimate attributable risk (AR). The 86 501 people notified with HCV
      contributed 422 761 person-years of observation; 0.8% had HIV, 3.7% HBV, and
      0.04% had both. RRs for males were equal to or lower than for females in younger
      ages, but higher in older ages (P for interaction ?0.013). HBV/HIV co-infection
      resulted in ARs of over 70% for liver disease and 30-60% otherwise. However, at
      the cohort level the impact was minimal (population ARs 1.3-8.7%). Our findings
      highlight the importance and success of public health measures, such as needle
      and syringe exchange programmes, which have helped to minimize the prevalence of
      co-infection in Australia. The findings also suggest that the age of study
      participants needs to be considered whenever the burden of HCV-related morbidity
      is reported by sex. The results are likely to be representative of patterns in
      hospital-related morbidity for the entire HCV-infected population in Australia
      and the ARs generalizable to other developed countries.

PMID- 21087541
TI  - First detection of spotted fever group rickettsiae in Ixodes ricinus and
      Dermacentor reticulatus ticks in the UK.
AB  - A preliminary study was conducted to determine the presence of spotted fever
      rickettsiae in two species of British tick (Ixodes ricinus and Dermacentor
      reticulatus). The 16S rRNA gene of Rickettsia spp. was detected in 39/401 (9.7%)
      of ticks tested, including 22/338 (6.5%) I. ricinus and 17/63 (27%) D.
      reticulatus. Some positive I. ricinus samples showed 100% homology with
      Rickettsia helvetica (10/22), and most positive D. reticulatus showed 100%
      homology with R. raoultii (13/17). Five other Rickettsia spp. were detected
      exhibiting 96-99% homology. Ticks positive for rickettsiae were collected from
      various hosts and from vegetation from eight counties across Great Britain. The
      distribution of R. helvetica in various engorged and unfed stages of I. ricinus
      suggests that R. helvetica is widespread. R. raoultii was found in questing adult
      D. reticulatus in Wales and England. This is the first evidence of potentially
      pathogenic spotted fever rickettsiae in British ticks.

PMID- 21087542
TI  - Antibiotic therapy for acute Q fever in The Netherlands in 2007 and 2008 and its
      relation to hospitalization.
AB  - Data about the effectiveness of different antibiotic regimens for the treatment
      of acute Q fever from clinical studies is scarce. We analysed the antibiotic
      treatment regimens of acute Q fever patients in 2007 and 2008 in The Netherlands
      and assessed whether hospitalization after a minimum of 2 days antibiotic therapy
      was related to the initial antibiotic therapy. Clinical data on antibiotic
      treatment and risk factors of acute Q fever patients were obtained from general
      practitioner medical records and self-reported by patients. For the 438 study
      patients, doxycycline was the most commonly prescribed initial antibiotic in both
      study years. After adjustments for confounding factors, doxycycline (200 mg/day),
      moxifloxacin, as well as other possibly effective antibiotics [including other
      new fluoroquinolones and doxycycline (100 mg/day)] showed significant lower risks
      for hospitalization compared to beta-lactam antibiotics and azithromycin
      (reference group), with the lowest risk for doxycycline (200 mg/day) (odds ratio
      0.04, 95% confidence interval 0.01-0.22). These data support current guidelines
      that recommend doxycycline as the first choice antibiotic for treating acute Q
      fever.

PMID- 21087543
TI  - Note on 'Age, influenza pandemics and disease dynamics' by Greer et al. (2010).

PMID- 21087544
TI  - Detecting new and emerging diseases on livestock farms using an early detection
      system.
AB  - The monitoring and surveillance of animal diseases is becoming increasingly
      important to policy-makers in Great Britain particularly given recent incursions
      of avian influenza and the emergence of bovine spongiform encephalopathy. To meet
      this surveillance objective, data from British livestock is collected and
      analysed retrospectively on an ongoing basis. However, these data can also be
      analysed prospectively within an early detection system which raises alerts to
      significant increases in disease reporting soon after they occur in the field.
      The feasibility of such an approach has been examined previously for Salmonella.
      This paper applied the approach to a further subset of surveillance data to alert
      those monitoring disease to increases in potentially new and emerging diseases.
      Thus far, the analysis, conducted on a quarterly basis, has proved a useful
      additional tool in enhanced surveillance by raising alerts to significant
      increases in several syndromes in both sheep and cattle.

PMID- 21087545
TI  - A new look at lunar soil collected from the sea of tranquility during the Apollo
      11 mission.
AB  - Complementary state-of-the-art optical, scanning electron, and X-ray microscopy
      techniques have been used to study the morphology of Apollo 11 lunar soil
      particles (10084-47). The combination of innovative lighting geometries with
      image processing of a through focal series of images has allowed us to obtain a
      unique collection of high-resolution light micrographs of these fascinating
      particles. Scanning electron microscopy (SEM) stereo-pair imaging has been
      exploited to illustrate some of the unique morphological properties of lunar
      regolith. In addition, for the first time, X-ray micrographs with submicron
      resolution have been taken of individual particles using X-ray ultramicroscopy
      (XuM). This SEM-based technique lends itself readily to the imaging of pores,
      cracks, and inclusions and allows the internal structure of an entire particle to
      be viewed. Rotational SEM and XuM movies have also been constructed from a series
      of images collected at sequential angles through 360 degrees . These offer a new
      and insightful view of these complex particles providing size, shape, and spatial
      information on many of their internal features.

PMID- 21087546
TI  - Micromorphology of epicuticular waxes and epistomatal chambers of pine species by
      electron microscopy and white light scanning interferometry.
AB  - High-resolution imaging and quantitative surface analysis of epicuticular waxes
      and epistomatal chambers of pine species were performed by field emission
      scanning electron microscopy and white light scanning interferometry. Both
      juvenile and adult needles were collected from the two-year-old seedlings of
      Pinus rigida and Pinus densiflora and subjected to surface observations.
      Epicuticular wax structures developed on the cuticle layer as well as in the
      epistomatal chambers and appeared to occlude the cavities in the two pine
      species. The stomata of P. densiflora were characterized by more distinctly
      raised rings around openings than P. rigida. The most common epicuticular wax
      structures of the two pine species included tubules with terminal openings and
      coiled rodlets. Wax platelets were deposited on epistomatal chambers. Either
      rodlets or tubules seemed to be longer and thicker in P. rigida than those in P.
      densiflora. White light scanning interferometry revealed quantitative surface
      profiles, demonstrating more ridged (ca. 4 MUm high) stomatal apertures and
      nearly twofold deeper (ca. 20 MUm deep) epistomatal chambers of P. densiflora
      than those of P. rigida. These results suggest that white light scanning
      interferometry can be applied to unravel the quantitative surface features of
      epicuticular sculptures on plant leaves.

PMID- 21087547
TI  - Critical consideration of precipitate analysis of Fe-1 at.% Cu using atom probe
      and small-angle neutron scattering.
AB  - An Fe-1 at.% Cu model alloy was examined by atom probe (3DAP) and small-angle
      neutron scattering (SANS) to verify the accordance of the gained results. The Fe
      Cu alloy was heat-treated for various times at 500 degrees C, forming Cu-rich
      precipitates within the Fe matrix. The chemical compositions of the precipitates
      and matrix found by 3DAP were used to calculate the magnetic scattering contrast.
      Additionally, a magnetic moment of the precipitates that contain a significant
      amount of Fe was taken into account for the calculation of magnetic scattering
      contrast. This in turn is used for the evaluation of the magnetic scattering
      curves gained by SANS. Both the 3DAP data as well as the scattering curves were
      analyzed with regard to radius, number density, and volume fraction of the
      precipitates as a function of aging time. The results yielded by both techniques
      are in good agreement and correspond to the development of the hardness of the
      alloy. Minor differences can be related to the cluster search algorithm used for
      the analysis of the 3DAP data as well as Fe overestimation based on different
      field phases.

PMID- 21087548
TI  - Characterization of mesoporosity in ceria particles using electron microscopy.
AB  - The geometry and three-dimensional (3D) morphology of the ceria particles
      synthesized by spray pyrolysis (SP) from two different precursors--cerium acetate
      hydrate and cerium nitrate hydrate (CeA and CeN ceria particles)--were
      characterized by transmission electron microscopy and electron tomography.
      Results were compared with surface area measurements, confirming that the surface
      area of CeA ceria particles is twice as large as that of CeN ceria particles.
      This result was supported by 3D microstructural observations, which have revealed
      that CeA ceria particles contain open pores (connected to surfaces) and closed
      pores (embedded in particles), while CeN ceria particles only contained closed
      pores. This experimental result suggests that the type of porosity is controlled
      by the precursors and could be related to their melting temperature during the
      heating process in SP.

PMID- 21087549
TI  - Microphotometry of underwater shadowing by a moss from a Niagara Escarpment
      waterfall.
AB  - Microscope and fiber-optic spectrophotometry of transmittance and backscattering
      both showed moss leaves to be capable of casting strong shadows, with a single
      leaf blocking approximately 90% of incident light from a point source. In leaves
      with only one layer of cells, the transmittance through the cytoplasm of single
      cells was similar to that for whole leaves. Analysis of cell wall birefringence
      by polarized-light interferometry indicated that cell walls might normally
      scatter rather than transmit light. Spectra transmitted through, or backscattered
      from, the upper green layers of moss were dominated by selective absorbance from
      chlorophyll, but there was also evidence of wavelength-dependent scattering, as
      detected in the lower layers of brown, dead moss. Specular reflectance from moss
      leaves was detected by polarimetry and may have contributed to the relatively
      high macroscopic transmittance of stationary moss in water. Shadowing by moss
      leaves was confirmed by dynamic measurements of mosses in turbulent water without
      bubbles. Flicker patterns from leaves were superimposed on the underwater flicker
      pattern created at the air-water interface, thus flecks of light were reduced in
      intensity, increased in frequency, and decreased in duration. This was detected
      with both point source and diffuse illumination of samples.

PMID- 21087550
TI  - Quantitative analysis of particle distributions by comparison with simulations.
AB  - In characterization of metal nanoparticle doped spherical composites, the two
      dimensional nature of transmission electron microscopy (TEM) images leads to
      ambiguities about the true location of the nanoparticles. Walking-in of simulated
      projections in comparison with actual TEM images leads to quantitative results
      such as location-dependent particle sizes and particle number density. This
      method takes advantage of the strength of fuzzy neural network computations via
      the human hunter-gatherer's visual system's evolved superiority while still
      allowing quantitative results by use of exact numerical simulations.

PMID- 21087551
TI  - Dislocation associated incubational domain formation in lightly gadolinium-doped
      ceria.
AB  - Nanosized incubational domain was observed in 10 at.% gadolinium-doped ceria
      (GDC) using high-resolution transmission electron microscopy. Dislocations were
      extensively observed in 10 at.% GDC instead of heavily doped 25 at.% GDC. By Fast
      Fourier Transform and Inverse Fast Fourier Transform analysis, it was noticed
      that the incubational domain existing in 10 at.% GDC has different lattice
      spacing and orientation from the neighboring ceria matrix. Furthermore,
      dislocations were usually observed in the interface region between the
      incubational domain and the ceria matrix. Based on experimental results, the
      formation mechanism of dislocation associated incubational domain in lightly
      gadolinium-doped ceria is rationalized.

PMID- 21087552
TI  - Partial agonists in schizophrenia--why some work and others do not: insights from
      preclinical animal models.
AB  - While dopamine D2 receptor partial agonists (PAs) have been long considered for
      treating schizophrenia, only one, aripiprazole, is clinically available for
      therapeutic use. This raises critically important questions as to what is unique
      about aripiprazole and to what extent animal models can predict therapeutic
      success. A number of PAs whose clinical fate is known: aripiprazole, preclamol,
      terguride, OPC-4392 and bifeprunox were compared to haloperidol (a reference
      antipsychotic) in several convergent preclinical animal models; i.e. amphetamine
      induced locomotion (AIL) and conditioned avoidance response (CAR), predictive of
      antipsychotic effects; unilateral nigrostriatal lesioned rats, a model of hypo
      dopaminergia; striatal Fos induction, a molecular marker for antipsychotic
      activity; and side-effects common to this class of drugs: catalepsy (motor side
      effects) and prolactaemia. The results were compared across drugs with reference
      to their measured striatal D2 receptor occupancy. All the PAs occupied striatal
      D2 receptors in a dose dependent manner, inhibited AIL and CAR, and lacked motor
      side-effects or prolactinaemia despite D2 receptor occupancy exceeding 80%. At
      comparative doses, aripiprazole distinguished itself from the other PAs by
      causing the least rotation in the hypo-dopaminergic model (indicating the least
      intrinsic activity) and showed the highest Fos expression in the nucleus
      accumbens (indicating functional D2 antagonism). Although a number of PAs are
      active in antipsychotic animal models, not all of them succeed. Given that only
      aripiprazole is clinically available, it can be inferred that low functional
      intrinsic activity coupled with sufficient functional antagonism as reflected in
      the animal models may be a marker of success.

PMID- 21087554
TI  - Introduction to the supplement: rare and challenging congenital cardiac lesions:
      an interdisciplinary approach.

PMID- 21087553
TI  - A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate
      induced acute panic-like responses.
AB  - Corticotropin releasing factor (CRF) is implicated in a variety of stress-related
      disorders such as depression and anxiety, and blocking CRF receptors is a
      putative strategy for treating such disorders. Using a well-studied animal model
      of panic, we tested the efficacy of JNJ19567470/CRA5626, a selective, non
      peptidergic CRF type 1 receptor (CRF1) antagonist (3, 10 and 40 mg/kg
      intraperitoneal injection), in preventing the sodium lactate (NaLac)-induced
      panic-like behavioural and cardiovascular responses. Adult male rats with chronic
      reduction of GABA levels (by inhibition of GABA synthesis with l-allyglycine, a
      glutamic acid decarboxylase inhibitor) in the dorsomedial/perifornical
      hypothalamus are highly anxious and exhibit physiological and behavioural
      responses to intravenous NaLac infusions similar to patients with panic disorder.
      These 'panic-prone' rats pre-treated with vehicle injections displayed NaLac
      induced increases in autonomic responses (i.e. tachycardia and hypertensive
      responses), anxiety-like behaviour in the social interaction test, and flight
      like increases in locomotor activity. However, systemically injecting such panic
      prone rats with the highest dose of CRF1 receptor antagonist prior to NaLac
      infusions blocked all NaLac-induced behaviour and cardiovascular responses. These
      data suggest that selective CRF1 receptor antagonists could be a novel target for
      developing anti-panic drugs that are as effective as benzodiazepines in acute
      treatment of a panic attack without the deleterious side-effects (e.g. sedation
      and cognitive impairment) associated with benzodiazepines.

PMID- 21087555
TI  - Anomalies of the coronary arteries: nomenclature and classification.
AB  - Abnormalities of the coronary arterial circulation represent a broad spectrum of
      anomalies. Some of these coronary arterial anomalies are of little clinical
      significance and are generally discovered either as incidental findings at
      autopsy or at the time of diagnostic coronary angiography in patients with
      atherosclerotic ischaemic cardiac disease. Some of these coronary arterial
      anomalies, however, are associated with a markedly abnormal natural history that
      may include significant cardiac morbidity very early in infancy, or increased
      risk of cardiac sudden death in childhood or adolescence. It is therefore
      important that we have a system for the naming and classification of these
      anomalies, to stratify them according to the associated risk and to develop
      rational approaches to evaluation and management. To apply any system of
      nomenclature reliably and responsibly, it is essential that each term be
      associated with a definition that is known and accepted by users of terminology.
      Such definitions are included in the specifications of both the Society of
      Thoracic Surgeons Congenital Heart Surgery Database and the European Association
      for Cardio-Thoracic Surgery Congenital Heart Surgery Database. These databases
      use the Diagnostic Short List of the version of the International Paediatric and
      Congenital Cardiac Code derived from the nomenclature of the International
      Congenital Heart Surgery Nomenclature and Database Project of the European
      Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons.
      This article will provide the nomenclature and definitions used by these
      databases for anomalies of the coronary arteries.

PMID- 21087556
TI  - Anomalous origin and course of the coronary arteries.
AB  - In the normal heart, the right and left coronary arteries arise from the aortic
      valvar sinuses adjacent to the pulmonary trunk. The right coronary artery then
      directly enters the right atrioventricular groove, whereas the main stem of the
      left coronary artery runs a short course before dividing to become the anterior
      interventricular and circumflex arteries. These arteries can have an anomalous
      origin from either the aorta or pulmonary trunk; their branches can have various
      anomalous origins relative to arterial pedicles. Other abnormal situations
      include myocardial bridging, abnormal communications, solitary coronary arteries,
      and duplicated arteries. Understanding of these variations is key to determining
      those anomalous patterns associated with sudden cardiac death. In the most common
      variant of an anomalous origin from the pulmonary trunk, the main stem of the
      left coronary artery arises from the sinus of the pulmonary trunk adjacent to the
      anticipated left coronary arterial aortic sinus. The artery can, however, arise
      from a pulmonary artery, or the right coronary artery can have an anomalous
      pulmonary origin. The key feature in the anomalous aortic origin is the potential
      for squeezing of the artery, produced by either the so-called intramural origin
      from the aorta, or the passage of the abnormal artery between the aortic root and
      the subpulmonary infundibulum.

PMID- 21087557
TI  - Echocardiographic imaging of anomalous origin of the coronary arteries.
AB  - In the past, coronary arterial anomalies have been difficult to diagnose by non
      invasive methods. Identification of coronary arterial origins is now a routine
      part of the standard paediatric echocardiogram. Anomalous origin of a coronary
      artery from the pulmonary trunk is an extremely important diagnosis to make. Many
      echocardiographic features are not directly related to the visualisation of the
      coronary arterial origin. Left ventricular dilation and abnormal ventricular
      performance are common, along with mitral regurgitation and evidence of
      collateralisation of the flow from the coronary artery that has an aortic origin.
      In some cases, the anomalous coronary artery can be seen to arise directly from
      the pulmonary trunk. Congenital atresia of the main stem of the left coronary
      artery has a similar echocardiographic presentation, except that its aortic
      origin is not determined. Anomalous aortic origin of the coronary artery has
      important implications, as the first presenting symptom can be sudden death. With
      meticulous attention to the origins of the coronary arteries, echocardiographic
      diagnosis can also be achieved. In contrast to the anomalous origin of a coronary
      artery from the pulmonary trunk, ventricular performance is usually normal.
      Whenever there is doubt as to the definition of the origin of the coronary
      arteries and, indeed, when there is serious clinical concern that a coronary
      artery has an anomalous origin, other testing, such as cine-computed tomography,
      magnetic resonance imaging, or cardiac catheterisation may be indicated for
      confirmation or to provide greater anatomic detail.

PMID- 21087558
TI  - Surgery and critical care for anomalous coronary artery from the pulmonary
      artery.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery is a rare
      congenital cardiac malformation that accounts for 0.25-0.50% of children with
      congenital cardiac disease and can cause myocardial dysfunction in young infants.
      In any infant presenting with ventricular dysfunction, the diagnosis of anomalous
      origin of the left coronary artery from the pulmonary artery must be suspected
      and the origin of the coronary arteries must be confirmed. The diagnosis of
      anomalous origin of the left coronary artery from the pulmonary artery is an
      indication for surgical repair. A two-coronary arterial system is the goal and is
      almost always achievable. The goal of surgical therapy is the creation of a two
      coronary arterial system, which appears to provide better long-term survival and
      protection from left ventricular dysfunction and mitral valvar regurgitation than
      does simple ligation of the anomalous coronary artery. Direct reimplantation of
      the anomalous coronary artery is the procedure of choice. It is straightforward
      and borrows from well-practised techniques commonly used in other procedures such
      as the arterial switch operation. For the rare patient in whom direct
      reimplantation is not possible, strategies to lengthen the anomalous coronary
      artery, or baffle it within the pulmonary root, are available. Mitral valvar
      regurgitation is common at presentation, but following the establishment of a two
      coronary arterial system and satisfactory myocardial perfusion, regurgitation of
      the mitral valve resolves in the vast majority. Therefore, mitral valvuloplasty
      at the time of initial surgery for anomalous origin of the left coronary artery
      from the pulmonary artery is not indicated. Post-operative care requires careful
      manipulation of inotropic support and reduction of afterload. Mechanical support,
      with either extracorporeal membrane oxygenation or left ventricular assist
      device, should be available for use if necessary.

PMID- 21087559
TI  - Anomalous aortic origin of a coronary artery: a universally applicable surgical
      strategy.
AB  - The most commonly reported coronary arterial malformation, in accounts of sudden
      deaths, is anomalous aortic origin of a coronary artery. Anomalous coronary
      arteries may arise from the left, right, or non-coronary sinuses of Valsalva.
      Importantly, although the left coronary artery from the right sinus has the worst
      prognosis, sudden death has been reported in all variants of origin from the
      various sinuses of Valsalva. This paper describes a technique that addresses all
      of the problems relating to anomalous aortic origin of a coronary artery from the
      wrong sinus of Valsalva. This technique includes the transection of the ascending
      aorta and pulmonary trunk, coronary arterial enlargement with a pericardial
      patch, and lateral translocation of the pulmonary trunk to the left pulmonary
      artery. Anomalous aortic origin of a coronary artery from the wrong sinus of
      Valsalva is a potentially lethal cardiac anomaly that can be corrected in all
      cases using this simplified surgical technique that addresses the major anatomic
      and physiological problems.

PMID- 21087560
TI  - The registry of anomalous aortic origin of the coronary artery of the Congenital
      Heart Surgeons' Society.
AB  - The anomalous aortic origin of a coronary artery from the wrong sinus of Valsalva
      with interarterial, intramural, and/or intraconal course is a rare congenital
      anomaly that is associated with a high risk of sudden death in children. The
      Congenital Heart Surgeons' Society established the Registry of Anomalous Aortic
      Origin of the Coronary Artery to help determine the outcome of children and young
      adults managed with surgical intervention versus observation and to test the
      hypothesis that subsets of patients with anomalous aortic origin of a coronary
      artery can be identified in whom the risk of intervention is less than the risk
      of observation. All institutional members of the Congenital Heart Surgeons'
      Society were recruited for participation. The registry consists of a
      retrospective cohort of patients diagnosed between 1 January, 1998 and 20
      January, 2009 and a prospective, population-based cohort of patients newly
      diagnosed from 21 January, 2009 onwards. Baseline demographics, diagnoses, and
      results of tests will be obtained through a review of the medical records. Annual
      follow-up data will be collected. Data will be analysed for different factors of
      risk at diagnosis, different strategies of treatment, and the impact of both on
      the outcomes of the patients. As of June 2010, 28 institutions had applied for
      approval from their institutional review board and 16 institutions had received
      approval from their institutional review board. Seventy-four patients have
      enrolled to date. We hope to use the established Pediatric Cardiomyopathy
      Registry as a guide to successful implementation, with a cooperative effort
      between institutions. The overall purpose of the Registry of Anomalous Aortic
      Origin of the Coronary Artery is to determine the outcome of surgical
      intervention versus observation in children and young adults with anomalous
      aortic origin of a coronary artery, and to describe the natural and "unnatural"
      history of these patients over the course of their lifetime. In this report, we
      describe the creation and design of the Registry of Anomalous Aortic Origin of
      the Coronary Artery. Data from the registry will be published at a later date.

PMID- 21087561
TI  - The electrocardiogram as an adjunct in diagnosing congenital coronary arterial
      anomalies.
AB  - Congenital coronary arterial abnormalities as isolated lesions are exceedingly
      rare. The electrocardiogram, while a reasonable adjunct in the diagnosis of
      coronary arterial abnormalities, should not supplant a good history and physical
      examination. Careful attention must be devoted to any signs or symptoms of
      ischaemic pain in the chest or syncope, which must not be overlooked. Exertional
      pain in the chest and exertional syncope should prompt an extensive evaluation by
      both the echocardiographer and the electrophysiologist. Clearance for
      participation in sports should be curtailed until a complete evaluation has ruled
      out the presence of any of the following disorders: a channelopathic mutation, a
      cardiomyopathy, or a congenital coronary arterial anomaly. Major abnormalities in
      the coronary arteries may present in the first few months of life or remain
      dormant until the exertional demands of adolescence unmask symptoms of myocardial
      ischaemia. Congenital coronary arterial anomalies may be analysed in the
      following major diagnostic groups: anomalous origin of the left coronary artery
      from the pulmonary artery, anomalous aortic origin of a coronary artery from the
      wrong aortic sinus of Valsalva, atresia of the left main coronary artery,
      myocardial bridges, and coronary arterial fistulas. The advent of state-of-the
      art modalities of imaging seems, at times, to have supplanted the
      electrocardiogram in making the diagnosis of potentially serious coronary artery
      abnormalities, especially in asymptomatic patients. However, as is also the case
      for a detailed history and physical examination, the electrocardiogram provides a
      potentially insightful look at the coronary arteries. Furthermore, the past
      decade has witnessed an increase in the use of the electrocardiogram as a
      screening tool in the assessment of the risk of sudden cardiac death in athletes
      in high school.

PMID- 21087562
TI  - Surgical management of congenital coronary arterial anomalies in adults.
AB  - Congenital anomalies of the coronary arteries are an uncommon, but important,
      cause of pain in the chest, myocardial ischaemia and even sudden cardiac death,
      especially in young individuals. This paper focuses on the surgical treatment of
      congenital anomalies of the coronary arteries in adults; indications for surgery
      and the different surgical options will be reviewed.

PMID- 21087563
TI  - Fistulous communications with the coronary arteries in the setting of hypoplastic
      ventricles.
AB  - Neonates born with hypoplastic left heart syndrome now have a remarkably improved
      prognosis compared with the situation existing before the development of the
      Norwood sequence of operative procedures. Some of those born with hypoplastic
      right ventricles in the setting of pulmonary atresia with an intact ventricular
      septum, however, still have a relatively poor prognosis. In part this reflects
      the presence of fistulous communication between the cavity of the right
      hypoplastic right ventricle and the coronary arterial tree. Such fistulous
      communications are now increasingly recognised as being important in the setting
      of hypoplastic left heart syndrome. In this brief review, we describe the anatomy
      of the communications. Those found with hypoplastic right ventricles are seen
      most frequently when the cavity of the ventricle effectively represents only the
      inlet, this in turn reflecting mural overgrowth of the apical trabecular and
      outlet components during foetal development. This almost certainly reflects an
      earlier appearance of the pulmonary valvar lesion that promotes the cavitary
      hypoplasia. In those with hypoplastic left ventricles, the key feature
      differentiating those with fistulous communications is the presence of a patent
      mitral valve, since the left ventricle is typically no more than a virtual slit
      in postero-inferior ventricular wall in the setting of mitral valvar atresia or
      absence of the left atrioventricular connection.

PMID- 21087564
TI  - Development of the outflow tracts with reference to aortopulmonary windows and
      aortoventricular tunnels.
AB  - Although malformations involving the ventricular outflow tracts are often
      described as conotruncal malformations, there is no consensus as to the lesions
      included in, or excluded from, this category, reflecting, in part, the current
      lack of precise definitions of the embryonic truncus and conus. Analysis of
      development of the outflow tract in terms of proximal, intermediate, and distal
      components greatly facilitates understanding of the morphology of the
      aortopulmonary window and aortoventricular tunnels. The aortopulmonary windows
      reflect failure to close the embryonic aortopulmonary foramen, the space between
      the distal end of the cushions that divide the lumen of the outflow tract itself
      and the dorsal wall of the aortic sac. The aortopulmonary tunnels are produced
      subsequent to abnormal development of the cushions themselves. The distal ends of
      these cushions excavate to produce the sinuses and leaflets of the arterial
      valves. The proximal parts of the cushions muscularise to form the subpulmonary
      infundibulum. The middle part of the cushion mass disappears to provide a tissue
      plane between the infundibulum and the aortic root. Abnormal formation of this
      area accounts for the various types of aortoventricular tunnel. In our brief
      review, we show how the anatomy of these lesions correlates with development of
      the outflow tract.

PMID- 21087565
TI  - Echocardiography of the aortopulmonary window, aorto-ventricular tunnels, and
      aneurysm of the sinuses of Valsalva.
AB  - There is a collection of rare congenital cardiac defects that can produce
      significant haemodynamic embarrassment. Owing to their rarity, these lesions may
      be overlooked or mistaken for other more common congenital cardiac defects. Using
      careful segmental echocardiographic techniques, such as multiple planes of
      imaging and inferential Doppler findings, it is possible to identify these
      lesions and thus plan surgical management. Some of the lesions of importance
      reviewed include the aortopulmonary window, the aorto-ventricular tunnels, the
      aorto-atrial tunnels, and aneurysm of the sinuses of Valsalva. Some conditions
      such as the aortopulmonary window and aneurysm of the sinuses of Valsalva often
      occur in the setting of other congenital cardiac lesions. At times, the presence
      of coexisting lesions may mask some of the characteristic features of these
      defects. With prompt identification, all of these rare conditions are amenable to
      complete surgical repair. Newer modalities such as three-dimensional
      echocardiography can further enhance surgical planning.

PMID- 21087567
TI  - Rare problems associated with the Fontan circulation.
AB  - The Fontan operation, originally described for the surgical management of
      tricuspid atresia, is now the final surgery in the strategy of staged palliation
      for a number of different forms of congenital cardiac disease with a functionally
      univentricular heart. Despite the improved technical outcomes of the Fontan
      operation, staged palliation does not recreate a normal physiology. Without a
      pumping chamber delivering blood to the lungs, the cardiovascular system is less
      efficient; cardiac output is generally diminished, and the systemic venous
      pressure is increased. As a result, patients with "Fontan physiology" may face a
      number of rare but potentially life-threatening complications including hepatic
      dysfunction, abnormalities of coagulation, protein-losing enteropathy, and
      plastic bronchitis. Despite the staged palliation resulting in remarkable
      survival, the possible complications for this group of patients are complex,
      involve multiple organ systems, and can be life threatening. Identifying the
      mechanisms associated with each of the rare complications, and developing
      strategies to treat them, requires the work of many people at many institutions.
      Continued collaboration between sub-specialists and between institutions will be
      required to optimise the care for this group of survivors with functionally
      univentricular hearts.

PMID- 21087568
TI  - The current surgical perspective to repair of atrioventricular septal defect with
      common atrioventricular junction.
AB  - Atrioventricular septal defect with common atrioventricular junction is a
      relatively common congenital cardiac malformation. It sometimes presents
      challenging surgical problems, especially when seen in combination with tetralogy
      of Fallot. We describe herein our current concepts regarding surgical repair of
      atrioventricular septal defect with and without tetralogy, discussing indications
      for surgery, timing, technical aspects, and outcomes.

PMID- 21087566
TI  - Unnatural history of the right ventricle in patients with congenitally malformed
      hearts.
AB  - The long-term outcome of patients with congenitally malformed hearts involving
      abnormal right ventricular morphology and haemodynamics is variable. In most
      instances, the patients are at risk for right ventricular failure, in part due to
      morphological differences between the right and left ventricles and their
      response to chronic volume and pressure overload. In patients after repair of
      tetralogy of Fallot, and after balloon valvotomy for valvar pulmonary stenosis,
      pulmonary regurgitation is the most significant risk factor for right ventricular
      dysfunction. In patients with a dominant right ventricle after Fontan palliation,
      and in those with systemic right ventricles in association with surgically or
      congenitally corrected transposition, the right ventricle is not morphologically
      capable of dealing with chronic exposure to the high afterload of the systemic
      circulation. In patients with Ebstein's malformation of the tricuspid valve, the
      degree of atrialisation of the right ventricle determines how well the right
      ventricle will function as the pump for the pulmonary vascular bed.

PMID- 21087569
TI  - An institutional approach to, and results for, patient with tetralogy with
      pulmonary atresia and major systemic-to-pulmonary collateral arteries.
AB  - BACKGROUND: Tetralogy of Fallot with pulmonary atresia and diminutive or absent
      intrapericardial pulmonary arteries is a rare congenital abnormality, with high
      morbidity and mortality. Despite great advances in surgical- and catheter-based
      therapies, management remains challenging and controversial. We describe the
      surgical methods and the results from our institution. METHODS: We performed a
      retrospective study of the medical records of patients included in our
      institutional database with tetralogy and pulmonary atresia, concentrating on
      those predominantly managed by our programme over their lifetime. We obtained
      demographics and records of all catheterisations and operations, and established
      mortality. We assessed the current state of those surviving in terms of clinical
      function at their most recent clinical evaluation and right ventricular function
      by echocardiography. RESULTS: We assessed 38 patients, with 89% follow-up. The
      mean number of catheterisations for each patients was 5, with a range from 1 to
      15. The mean number of operations was 2.2, with a range from 1 to 6.
      Unifocalisation had been performed in 26 patients, with 12 undergoing procedures
      to recruit the native pulmonary vasculature. Of the overall cohort, eight
      patients died. The ventricular septal defect had been closed in all but two
      patients. Most patients have no or mild exercise intolerance. Right ventricle
      dysfunction has been a continuing hazard for 15 years. CONCLUSIONS: An
      individualised approach, using unifocalisation as well as aggressive attempts to
      recruit the available native pulmonary vasculature, achieves outcomes in the
      intermediate term superior to the natural history of the lesions, and comparable
      with those of other studies.

PMID- 21087570
TI  - The role of the cardiologist in the evaluation of dysautonomia.
AB  - Dysfunction of the autonomic nervous system, or dysautonomia, is an uncommon
      disease. Postural orthostatic tachycardia syndrome is one of the several types of
      dysautonomia. Postural orthostatic tachycardia syndrome, also known as chronic
      orthostatic intolerance, is the most common but least severe of the dysautonomic
      disorders; it will serve as the model for evaluation and management of the other
      dysautonomias. Overall, these patients can have variable dysfunction of the
      autonomic nervous system that is more severe than that observed in typical
      neurocardiogenic syncope. Frequently, providers are not familiar with either the
      evaluation or the management of this syndrome, or are just not interested in
      doing so. This article attempts to describe strategies for evaluation and
      management of postural orthostatic tachycardia syndrome. The diagnosis of
      postural orthostatic tachycardia syndrome is made by the finding of orthostatic
      intolerance associated with a pulse greater than 120 beats per minute in the
      first 10 minutes of upright position or an elevation in pulse greater than 30
      beats per minute in the first 10 minutes of upright position. Overall, these
      patients can have variable dysfunction of the autonomic nervous system that is
      more severe than that seen in typical neurocardiogenic syncope. A wide variety of
      associated symptoms may exist and these symptoms can have tremendous impact on
      the lives of the patients and their families. Management of these patients can be
      difficult as well as rewarding. It is helpful to perform an extensive education
      up front with these patients and their families. Interventions for patients with
      postural orthostatic tachycardia syndrome typically fall into two broad
      categories: non-pharmacological and pharmacological. Non-pharmacological
      therapies are varied, but are based primarily on ensuring adequate status of
      intravascular fluid. Polypharmacy may be required to control symptoms associated
      with postural orthostatic tachycardia syndrome. On account of the severity of
      their symptoms, these patients frequently have difficulty in completing their
      school assignments. The physician may need to help support the attempts of the
      family to work with the school to help the patient stay in school. As postural
      orthostatic tachycardia syndrome is underdiagnosed and poorly understood, it is a
      disease that provides an excellent opportunity to perform research. The most
      important studies would be those that aim to elucidate an aetiology and a
      pathophysiology of postural orthostatic tachycardia syndrome. In the final
      analysis, the role of the cardiologist in the evaluation and management of a
      patient with dysautonomia is to help a patient with severe disability to feel as
      if they are normal, or much closer to it.

PMID- 21087571
TI  - Commentary on the adoption of the electronic health record.
AB  - The promise of the electronic health record is to provide multiple functions
      including the ability to easily share information among providers, the ability to
      order studies, the ability to improve the safety of patients, and the ability to
      coordinate plans of care. Efforts to achieve these goals face multiple challenges
      including large expenditures of money, large expenditures of time and effort, and
      a persistent communication gap between the designers and the users of these
      electronic medical records.

PMID- 21087572
TI  - Patient-reported outcomes in congenital cardiac disease: are they as good as you
      think they are?
AB  - Patient-reported outcomes are "any outcome based on data provided by patients or
      patient proxy as opposed to data provided from other sources". Examples of
      patient-reported outcomes are quality of life, well-being, functional status,
      symptoms, adherence to treatment, satisfaction with treatment, and utility or
      preference-based measures. The main question of this manuscript is whether
      patient-reported outcomes in patients with congenital cardiac disease are as good
      as we think they are. In general, we could say yes, because numerous studies show
      that patients with congenital cardiac disease have an excellent quality of life.
      By contrast, we could say no, because patients generally overestimate their
      functioning, and up to two out of three patients are not compliant with the
      prescribed therapy or recommendations for follow-up. However, most importantly,
      we have to say that we do not know whether the patient-reported outcomes are
      good, because research with patient-reported outcomes in congenital cardiac
      disease is limited. Hence, patient-reported outcomes should be a priority on the
      agenda for research in the domain of congenital cardiac disease.

PMID- 21087573
TI  - Feeding, growth, and nutrition in children with congenitally malformed hearts.
AB  - In the United States of America, approximately 40,000 infants are born annually
      with congenitally malformed hearts. Children with defects that require complex
      surgical palliation, or definitive repair, face many challenges in achieving
      optimal short-term and long-term growth. The presence of associated chromosomal
      abnormalities, cyanosis, and cardiac failure adds to the complexity and
      challenge. In this review, we address three themes related to feeding, growth,
      and nutrition of infants after neonatal cardiac surgery: nutritional challenges
      after chylothorax; breastfeeding after surgery; and the challenges of feeding
      after discharge. Chylothorax is a rare complication following cardiothoracic
      surgery in children. Children with chylothorax have nutritional depletion
      secondary to protein losses in chylous fluid, hypovolaemia, and electrolyte
      losses. In spite of the evidence supporting the use of human milk and
      breastfeeding in preterm infants, barriers to its use appear to persist in
      infants with critical cardiac disease. Yet, human milk is the preferred form of
      nutrition for well, preterm, or ill infants. It is well documented that after
      complex neonatal cardiac surgery medical teams and families struggle with infant
      feeding problems. Parents have described feeding their children as difficult,
      time consuming, and anxiety producing. Medical complications such as chylothorax,
      limited access to human milk, and parental concerns and stress about feeding are
      but three of the myriad of factors that may contribute to poor outcomes regarding
      nutrition and growth. Compelling evidence exists that this multi-factorial
      problem must be addressed with both physiological and behavioural strategies.

PMID- 21087574
TI  - 9th Annual William J. Rashkind Memorial Lecture in paediatric cardiology: "the
      reimbursement tsunami: preserving the passion".
AB  - In the early 1980s cardiology was dominated by "triple threat individuals" -
      doctors who were the very best clinicians, very best researchers, and very best
      teachers. This type of individual usually became the director of the division.
      Now, however, the amount of knowledge and specialisation in each of these three
      areas of expertise has exploded. It is not certain that triple threat individuals
      can or do exist today. Instead, we need to be aiming higher, for a "quintuple
      threat profession". Not only do we need expertise in clinical care, teaching, and
      research, but also we now require business leadership and alignment. No single
      person can be expert in all five of these areas. In paediatric cardiology we need
      to invest in the right people. Our new "quintuple threat profession" needs to
      match the expertise and passion of the right people with our current and future
      needs. Going forward, we should focus on leadership, teams, and alignment. We
      need to identify, develop, and empower leaders at all levels within our
      profession, including physicians, nurses, and hospital administrators.
      Ultimately, we need a profession that remains clinically led, but professionally
      managed. The second step of the formula is the development of successful teams,
      and teamwork. Successful "team behaviour" is not a part of traditional medical
      education. The third step is alignment. Alignment can be defined as representing
      the degree to which physicians and organisations, such as hospitals, acting out
      of enlightened self-interest, operate inside a common vision, mutual goals, and
      the acceptance of a shared destiny. Imagine the benefits to our profession and
      our kids if we can provide a new level of leadership, teamwork, and alignment
      going forward.

PMID- 21087575
TI  - Immune responses against Marek's disease virus.
AB  - It is more than a century since Marek's disease (MD) was first reported in
      chickens and since then there have been concerted efforts to better understand
      this disease, its causative agent and various approaches for control of this
      disease. Recently, there have been several outbreaks of the disease in various
      regions, due to the evolving nature of MD virus (MDV), which necessitates the
      implementation of improved prophylactic approaches. It is therefore essential to
      better understand the interactions between chickens and the virus. The chicken
      immune system is directly involved in controlling the entry and the spread of the
      virus. It employs two distinct but interrelated mechanisms to tackle viral
      invasion. Innate defense mechanisms comprise secretion of soluble factors as well
      as cells such as macrophages and natural killer cells as the first line of
      defense. These innate responses provide the adaptive arm of the immune system
      including antibody- and cell-mediated immune responses to be tailored more
      specifically against MDV. In addition to the immune system, genetic and
      epigenetic mechanisms contribute to the outcome of MDV infection in chickens.
      This review discusses our current understanding of immune responses elicited
      against MDV and genetic factors that contribute to the nature of the response.

PMID- 21087576
TI  - Epidemiology and horizontal transmission of porcine circovirus type 2 (PCV2).
AB  - Porcine circovirus type 2 (PCV2) is a small, non-enveloped, circular, single
      stranded DNA virus of economic importance in the swine industry worldwide. Based
      on the sequence analyses of PCV2 strains, isolates can be divided into five
      subtypes (PCV2a-e). PCV2 is an ubiquitous virus based on serological and viremia
      data from countries worldwide. In addition, PCV2 DNA was discovered in archived
      samples prior to the first recognition of clinical disease. Recently, a worldwide
      shift in PCV2 subtype from PCV2a to PCV2b occurred. PCV2 DNA can be detected in
      fecal, nasal, oral and tonsillar swabs as well as in urine and feces from both
      naturally and experimentally infected pigs. PCV2 DNA can be detected early in the
      infectious process and persists for extended periods of time. The effectiveness
      of disinfectants for reducing PCV2 in vitro is variable and PCV2 is very stable
      in the pig environment. Limited data exist on the horizontal transmission of
      PCV2. Direct transmission of PCV2 between experimentally or naturally infected
      animals and naive animals has been documented and the incorporation of clinical
      or subclinically infected animals into a population represents a risk to the
      herd. Indirect transmission through the oral, aerosol or vaccine routes is likely
      a lesser risk for the transmission of PCV2 in most swine populations but may be
      worth evaluating in high heath herds. The objective of this review was to discuss
      data on the epidemiology and horizontal transmission of PCV2.

PMID- 21087577
TI  - Semiautomatic algorithm for lymph node analysis corrected for partial volume
      effects in combined positron emission tomography-computed tomography.
AB  - Positron emission tomography-computed tomography (PET-CT) is superior compared to
      stand-alone PET in evaluation of malignancies. Few studies have employed high
      resolution structural information to correct PET. We designed a semiautomatic
      algorithm using CT and PET to obtain a partial volume corrected (PVC)
      standardized uptake value (SUV) and a combined morphologic and functional
      parameter (multimodal SUV) for lymph node assessment. Lesions were segmented by a
      semiautomatic algorithm in CT images. Lesion volume was used for PVC and for
      calculating the multimodal SUV. The method was applied to 47 lymph nodes (30
      patients) characterized as suspicious in 18F-fluorodeoxyglucose-PET-CT. In
      phantoms, PVC improved significantly the measured uptake of the lesion. In
      patients, 36 lymph nodes could be segmented without problems; in 11 lesions, a
      manual interaction was necessary. SUVs before PVC (mean 1.29) increased
      significantly (p < .0005) after PVC (mean 2.8). If SUV 2.5 was used as a
      threshold value to distinguish between benign and malignant lesions, 11 of the 47
      lesions changed from benign to malignant after the PVC. The mean multimodal SUV
      was 0.39 mL for the benign lesions and 4.47 mL for the malignant lesions. In this
      work we presented a method for quantitative analysis of lymph nodes in PET-CT.
      PVC leads to significant differences in SUV.

PMID- 21087579
TI  - The potential for a concerted system for the rapid monitoring of excess mortality
      throughout Europe.
AB  - We present the results of a survey conducted in the context of the project
      European Monitoring of Excess Mortality for Public Health Action (EuroMOMO),
      which is being conducted to develop a routine public health mortality monitoring
      system for the timely detection of excess deaths related to public health threats
      in Europe. The survey was conducted in 32 European countries using two
      questionnaires on: i) the existing and planned mortality monitoring systems, and
      ii) the routine collection of mortality data. Nine existing mortality monitoring
      systems were identified in seven countries (Belgium, Germany, France (two
      systems), Italy (two systems), Portugal, Spain, and Switzerland), as well as
      several systems that were in a pilot or planning state. Each system is described
      in detail. The results will be used for the subsequent phases of EuroMOMO, in
      particular for identifying the minimum requirements for the planned European
      system and for selecting countries to be included in the project's pilot phase.

PMID- 21087580
TI  - Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass
      spectrometry as a tool for rapid diagnosis of potentially toxigenic
      Corynebacterium species in the laboratory management of diphtheria-associated
      bacteria.
AB  - The rapid identification of the potentially toxigenic Corynebacterium species, C.
      diphtheriae, C. ulcerans and C. pseudotuberculosis is essential for diagnosis and
      treatment of diphtheria and diphtheria-like diseases. We used matrix-assisted
      laser desorption/ionisation time-of-flight mass spectrometry (MALDIT-OF MS) in
      comparison with classical microbiological and molecular methods on 116
      Corynebacterium strains. All 90 potentially toxigenic Corynebacterium strains
      collected by the German National Consiliary Laboratory on Diphtheria in a period
      of more than ten years were correctly identified by MALDI-TOF MS. We propose an
      algorithm for fast and reliable diagnosis of diphtheria incorporating MALDI-TOF
      MS, real-time tox PCR and Elek testing.

PMID- 21087582
TI  - Spotlight on measles 2010: ongoing measles outbreak in Northern Ireland following
      an imported case, September-October 2010.
AB  - We report an ongoing outbreak of measles with five laboratory-confirmed and four
      epidemiologically linked cases in Northern Ireland as at 26 October 2010. The
      index case was an unvaccinated non-Northern Ireland resident with subsequent
      genotyping suggesting that infection originated in the usual country of residence
      of this case. Confirmed cases include one patient with a history of two measles
      mumps-rubella vaccine doses.

PMID- 21087584
TI  - The field epidemiology manual (FEM) wiki: a collaborative eLearning online portal
      to be launched at ESCAIDE.

PMID- 21087581
TI  - Molecular surveillance of pandemic influenza A(H1N1) viruses circulating in Italy
      from May 2009 to February 2010: association between haemagglutinin mutations and
      clinical outcome.
AB  - Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in
      Italy were examined, focusing on amino acid changes at position 222 because of
      its suggested pathogenic relevance. Among 169 patients, the D222G substitution
      was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild
      cases, whereas the D222E mutation was more frequent and evenly distributed in
      mild (31.6%) and severe cases (38.4%). A cluster of D222E viruses among school
      children confirms reported human-to-human transmission of viruses mutated at
      amino acid position 222.

PMID- 21087585
TI  - Guidelines for the laboratory diagnosis of genital herpes in eastern European
      countries.
AB  - These guidelines aim to provide comprehensive information about sexually
      transmitted herpes simplex virus (HSV) infection and its laboratory diagnosis in
      eastern European countries. They are primarily intended for professionals testing
      specimens from patients at a sexual healthcare clinic but may also be helpful for
      community-based screening programmes. In particular, the guidelines recommend:
      (i) either viral culture or validated and approved nucleic acid amplification
      tests (NAATs) as the tests of choice for symptomatic patients, which should be
      promoted for laboratory confirmation of HSV infection; (ii) if culture or NAATs
      are not available, antigen detection--a direct immunofluorescence test or enzyme
      immunoassay from samples from symptomatic patients--could be employed, but HSV
      type determination is of importance; (iii) only type-specific serology should be
      used for detecting asymptomatic individuals, testing pregnant women at risk of
      acquiring HSV infection close to delivery, men who have sex with men and people
      who are HIV positive; (iv) widespread screening for HSV antibodies should be
      discouraged; and (v) any non-validated diagnostic tests should be validated
      against a recommended, approved gold standard.

PMID- 21087586
TI  - Differences in national influenza vaccination policies across the European Union,
      Norway and Iceland 2008-2009.
AB  - In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine
      European New Integrated Collaboration Effort (VENICE) project across 27 European
      Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in
      official national seasonal influenza vaccination policies since a survey
      undertaken in 2008 and to compare the estimates of vaccination coverage between
      countries using data obtained from both surveys. Of 27 responding countries, all
      recommended vaccination against seasonal influenza to the older adult population.
      Six countries recommended vaccination of children aged between six months and <18
      years old. Most countries recommended influenza vaccination for those individuals
      with chronic medical conditions. Recommendations for vaccination of healthcare
      workers (HCW) in various settings existed in most, but not all countries. Staff
      in hospitals and long-term care facilities were recommended vaccination in 23
      countries, and staff in out-patient clinics in 22 countries. In the 2009 survey,
      the reported national estimates on vaccine coverage varied by country and risk
      group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9%
      -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries
      that recommend the influenza vaccination do not monitor the coverage in risk
      groups. In 2008 and 2009 most countries recommended influenza vaccination for the
      main risk groups. However, despite general consensus and recommendations for
      vaccination of high risk groups, many countries do not achieve high coverage in
      these groups. The reported vaccination coverage still needs to be improved in
      order to achieve EU and World Health Organization goals.

PMID- 21087587
TI  - National outbreak of Salmonella Typhimurium (Dutch) phage-type 132 in the
      Netherlands, October to December 2009.
AB  - Between October and December 2009, 23 cases of Salmonella Typhimurium (Dutch)
      phage type 132, each with an identical multiple-locus variable-number tandem
      repeat analysis (MLVA) profile (02-20-08-11-212), were reported from across the
      Netherlands. A case-control study was conducted using the food-consumption
      component of responses to a routine population-based survey as a control group.
      The mean age of cases was 17 years (median: 10 years, range: 1-68). Sixteen cases
      were aged 16 years or under. Raw or undercooked beef products were identified as
      the probable source of infection. Consumers, in particular parents of young
      children, should be reminded of the potential danger of eating raw or undercooked
      meat.

PMID- 21087588
TI  - Cohort study of a campylobacteriosis outbreak associated with chicken liver
      parfait, United Kingdom, June 2010.
AB  - In an outbreak of 24 cases of gastroenteritis among guests at a wedding
      reception, 13 cases had confirmed Campylobacter infection. In a cohort study,
      univariate analysis revealed a strong association with consumption of chicken
      liver parfait: risk ratio (RR): 30.08, 95% confidence interval (CI): 4.34-208.44,
      p<0.001, which remained after adjustment for potential confounders in a
      multivariable model: RR=27.8, 95% CI=3.9-199.7, p=0.001. These analyses strongly
      support the hypothesis that this outbreak was caused by the consumption of
      chicken liver parfait.

PMID- 21087589
TI  - The European Centre for Disease Prevention and Control launches call for external
      experts.

PMID- 21087590
TI  - Outbreak of 2009 pandemic influenza A(H1N1) in a Finnish garrison--a serological
      survey.
AB  - In September 2009, an outbreak of 2009 pandemic influenza A(H1N1) took place in a
      Finnish garrison. In November 2009, we performed a serological survey among 984
      recruits undergoing their military service at the garrison and related the
      results to self-reported upper respiratory tract infection (URTI) with or without
      fever. Of 346 volunteers who donated a blood sample, 169 (49%) had pandemic
      influenza A(H1N1) virus-specific antibodies. Of those, 84 (50%) reported no
      recent history of URTI, suggesting that a major part of those infected with
      pandemic influenza A(H1N1) virus may be asymptomatic.

PMID- 21087591
TI  - Introduction and control of three invasive mosquito species in the Netherlands,
      July-October 2010.
AB  - In July 2010, during routine mosquito surveillance inspections at companies that
      import used tires, three invasive species were found at five locations in the
      Netherlands: the yellow fever mosquito (Aedes aegypti), the Asian tiger mosquito
      (Ae. albopictus), and the American rock-pool mosquito (Ae. atropalpus). This is
      the first time that Ae. aegypti is reported from the Netherlands. Mosquito
      control was initiated one week after the first invasive mosquito was found, using
      adulticides and larvicides. The available data suggest that the implemented
      control measures have been effective for this season.

PMID- 21087592
TI  - Increasing case numbers of adenovirus conjunctivitis in Germany, 2010.
AB  - In 2010 (as of 13 October 2010), the number of adenovirus conjunctivitis cases
      reported to the Robert Koch Institute in Berlin, Germany, has increased by more
      than 250% compared with same period in the previous two years. An investigation
      was initiated to identify spatial or temporal clusters, possible sources of
      infection and potential connections to cases abroad. The analysis did not show a
      disproportionately affected sex or age group, but many infections were preceded
      by exposure to ophthalmological facilities, communal facilities or public places.

PMID- 21087593
TI  - Increased incidence of Mycoplasma pneumoniae infections detected by laboratory
      based surveillance in Denmark in 2010.
AB  - In Denmark recurrent epidemics of Mycoplasma pneumoniae infections have been
      described since the 1950s at intervals of approximately four to six years. The
      latest epidemic occurred in 2004/05 followed by two years of high incidence and
      more than three years of low incidence. Due to a recent increase in diagnosed
      cases since late summer 2010, we conducted a survey of positive M. pneumoniae PCR
      tests performed by clinical microbiology departments in Denmark, which indicated
      that a new epidemic may be underway.

PMID- 21087594
TI  - The acute toxicity of fipronil to two non-target invertebrates associated with
      mosquito breeding sites in Australia.
AB  - Mosquito-borne arboviruses are a significant health issue in the irrigation areas
      of south-eastern Australia. Fipronil, a pyrazole insecticide with strong activity
      against larval Culex species, was tested for its acute effects on Simocephalus
      elizabethae (Daphniidae) and Polypedilum nubiferum (Chironomidae), two non-target
      invertebrates associated with Australian rice field mosquito habitats. Technical
      and formulated fipronil were assessed in the presence or absence of particulate
      artificial diets in 48 h static bioassays. LC(50) values for neonate S.
      elizabethae ranged from 11.13 to 19.12 MUgl(-1) whilst those for final instar P.
      nubiferum ranged from 0.89 to 2.18 MUgl(-1). Feeding during exposure
      significantly reduced the susceptibility of P. nubiferum to both technical and
      formulated fipronil. The effect of feeding was less consistent in Simocephalus
      bioassays, where much less food was present. We investigated whether adsorption
      to unconsumed food particles may have limited fipronil bioavailability by using
      solid-phase microextraction and gas chromatography to measure the available
      fipronil from fed and unfed systems 24h after establishment. Differences between
      the systems were not significant (P>0.05). The significantly higher LC(50) values
      in the fed Polypedilum bioassays do not appear to be a consequence of reduced
      fipronil bioavailability. Observed differences in toxicity probably reflect
      increased stresses associated with food deprivation in the unfed bioassays. Our
      results support published data on the toxicity of fipronil to aquatic
      invertebrates which suggest that the use of this material as a mosquito larvicide
      may cause disruption to aquatic ecosystems.

PMID- 21087595
TI  - Theoretical levels of control as a function of mean temperature and spray
      efficacy in the aerial spraying of tsetse fly.
AB  - The hypothetical impact of aerial spraying on tsetse fly populations is
      investigated. Spray cycles are scheduled at intervals two days short of the first
      interlarval period and halted once the last of the female flies that originated
      from pre-spray-deposited pupae have been sprayed twice. The effect of temperature
      on the aerial spraying of tsetse, through its reproductive cycle and general
      population dynamics, is of particular interest, given that cooler weather is
      preferred for the settling of insecticidal droplets. Spray efficacy is found to
      come at a price due to the greater number of cycles necessitated by cooler
      weather. The extra cost is argued to be worth while. Pupae, still in the ground
      at the end of spraying, are identified as the main threat to a successful
      operation. They are slightly more vulnerable at the low temperature extreme of
      tsetse habitat (16 degrees C), when the cumulative, natural pupal mortality is
      high. One can otherwise base one's expectations on the closeness with which the
      time to the third last spray approaches one puparial duration. A disparity of
      anything close to the length of a spray cycle advocates caution, whereas one
      which comes close to vanishing should be interpreted as being auspicious. Three
      such key temperatures, just below which one can anticipate an improved outcome
      and just above which caution should be exercised, are 17.146 degrees C, 19.278
      degrees C and 23.645 degrees C. A refinement of the existing formulae for the
      puparial duration and the first interlarval period might be prudent in the South
      African context of a sympatric Glossina brevipalpis-Glossina austeni, tsetse
      population. The resulting aerial spraying strategy would then be formulated using
      a G. brevipalpis puparial duration and a G. austeni first interlarval period.

PMID- 21087596
TI  - Multistate unfolding of alpha-mannosidase from Canavalia ensiformis (Jack Bean):
      evidence for the thermostable molten globule.
AB  - The relevance of partially ordered states of proteins (such as the molten-globule
      state) in cellular processes is beginning to be understood. We examined the
      conformational transitions in a multimeric and high molecular weight class II
      alpha-mannosidase from Canavalia ensiformis (Jack Bean) (Jbalpha-man) utilizing
      intrinsic fluorescence, solute quenching, hydrophobic dye binding, size exclusion
      chromatography and circular dichroism (CD) spectroscopy for the protein in
      presence of Guanidine hydrochloride (GdnHCl). The decomposition analysis of the
      protein spectra obtained during unfolding showed progressive appearance of class
      S, I, II and III trp. The parameter A and spectral center of mass showed multi
      state unfolding of the protein and phase diagram analysis revealed formation of
      an intermediate of Jbalpha-man in the vicinity of 1 M GdnHCl. The intermediate
      exhibited compact secondary and distorted tertiary structure with exposed
      hydrophobic amino acids on the surface, indicating the molten-globule nature. The
      dissociation, partial unfolding and aggregation of Jbalpha-man occurred
      simultaneously during chemical denaturation. The molten-globule possessed
      slightly higher hydrodynamic radius, perturbance in the structure up to 60 
      degrees C and stability of the structure up to 80  degrees C unlike the native
      Jack Bean alpha-mannosidase. The modes of chemical and thermal denaturation of
      the native protein were different. The solute quenching parameters confirmed the
      altered confirmation of the intermediate. Taken together, our results constitute
      one of the early reports of formation of GdnHCl induced molten globule in a class
      II alpha-mannosidase.

PMID- 21087597
TI  - Synergistic antimicrotubule therapy for prostate cancer.
AB  - Prostate cancer has been widely viewed as a chemoresistant neoplasm. Perhaps, the
      most prevalent antimicrotubule strategy involves docetaxel administration at its
      maximum-tolerated dose (MTD). Although the goal is to obtain total eradication of
      cancer cells, debilitating toxicities are presented by docetaxel therapy,
      including myelosuppression, immunosuppression, gastrointestinal toxicity and
      peripheral neuropathy. In addition, solubility limitations necessitate infusion
      of high-doses intravenously once or twice a week followed by a rest period, which
      allows recovery of normal proliferating cells to counter-balance efficacy. An
      emerging notion is that more of a toxic drug at its MTD is not necessarily
      better. It is likely that combinatorial antimicrotubule therapy with drugs
      occupying different sites on tubulin may enhance efficacy while reducing
      toxicity. Here we show that bromonoscapine (EM011), a microtubule-modulating
      noscapine analog, displays synergism with docetaxel as seen by cell viability and
      proliferation assays. Cell-cycle data demonstrated that lower dose-levels of
      docetaxel (25nM) in combination with EM011 caused an additive increase in
      proapoptotic activity. Since docetaxel alone caused severe mitotic arrest
      followed by mitotic slippage and endoreduplication, we strategized a sequential
      treatment regime that involved initial pretreatment with docetaxel followed by
      addition of EM011 to maximize mitotic arrest and subsequent apoptosis. In vivo
      studies with docetaxel and EM011 in combination showed a marked inhibition of
      tumor growth compared to docetaxel or EM011 as single-agents. Our studies suggest
      the potential usefulness of EM011 in the clinic to enhance docetaxel activity.
      This would reduce toxicity, thus improving the quality of life of docetaxel
      treated patients.

PMID- 21087598
TI  - Eriodictyol: a flavonoid antagonist of the TRPV1 receptor with antioxidant
      activity.
AB  - The transient potential vanilloid 1 receptor (TRPV1) is a calcium-permeable
      channel responsible for the transduction and modulation of acute and chronic pain
      signaling. As such, this receptor is a potential target for the treatment of a
      number of pain disorders. However, AMG517, a TRPV1 antagonist, presents several
      clinical limitations that include the induction of severe hyperthermia. The aim
      of this study was to investigate the possible interaction of the flavonoid
      eriodictyol with the TRPV1 receptor and to determine its putative antinociceptive
      and hyperthermic effects. Eriodictyol was able to displace [(3)H]-resiniferatoxin
      binding (IC(50)=47; 21-119nM) and to inhibit calcium influx mediated by capsaicin
      (IC(50)=44; 16-125nM), suggesting that eriodictyol acts as a TRPV1 antagonist.
      Moreover, eriodictyol induced antinociception in the intraplantar capsaicin test,
      with maximal inhibition of 49+/-10 and 64+/-4% for oral (ID(50)=2.3; 1.1
      5.7mg/kg) and intrathecal (ID(50)=2.2; 1.7-2.9nmol/site) administration,
      respectively. Eriodictyol did not induce any change in body temperature or
      locomotor activity. Orally administered eriodictyol (4.5mg/kg) prevented the
      nociception induced by intrathecal injections of capsaicin, as well as the non
      protein thiol loss and 3-nitrotyrosine (3-NT) formation induced by capsaicin in
      spinal cord. Eriodictyol also reduced the thermal hyperalgesia and mechanical
      allodynia elicited by complete Freund's adjuvant (CFA) paw injection. In
      conclusion, eriodictyol acts as an antagonist of the TRPV1 receptor and as an
      antioxidant; it induces antinociception without some of the side effects and
      limitations such as hyperthermia that are expected for TRPV1 antagonists.

PMID- 21087599
TI  - ABC50 modulates sensitivity of HL60 leukemic cells to endoplasmic reticulum (ER)
      stress-induced cell death.
AB  - ABC50 (aka ABCF1) is a member of the ATP Binding Cassette protein family. ABC50
      stimulates complex formation between eIF2, GTP and Met-tRNA implicating it in
      translation initiation. Econazole (Ec) is an imidazole anti-fungal that induces
      endoplasmic reticulum (ER) stress in mammalian cells by promoting ER Ca(2+)
      depletion and sustained protein synthesis inhibition. HL60 cells selected for Ec
      resistance were found to exhibit a multi-drug resistance phenotype associated
      specifically with ER stress. Differential Display was used to identify ABC50 as
      an overexpressed gene in resistant cells. ABC50 knockdown (KD) in Ec-resistant
      HL60 cells partially restored Ec sensitivity. In parental HL60 cells, ABC50 KD
      increased sensitivity to Ec, thapsigargin and tunicamycin but not to serum
      withdrawal or etoposide. ABC50 overexpression (OE) partially and specifically
      decreased sensitivity to ER stress agents. ABC50 KD or OE had no effect on ROS
      generation by Ec, ER Ca(2+) stores or thapsigargin-stimulated influx. Increased
      eIF2alpha phosphorylation in response to ER stress was observed in the KD cells
      while decreased phosphorylation was observed in the OE cells. Ribosomal content
      was reduced in ABC50 KD cells and increased in OE cells. Knockdown suppressed
      protein synthesis while OE increased it. Protein synthesis was sustained in ABC50
      OE cells exposed to Ec. ABC50 OE promoted ER stress resistance and increased
      antibody production in the hybridoma GK1.5 suggesting it may be useful for the
      overproduction of specific proteins. Taken together, these results indicate that
      ABC50 modulates sensitivity to Ec and other ER stress agents primarily through
      its effects on protein synthesis.

PMID- 21087600
TI  - Characterization of the c.(-203)A>G variant in the glucocerebrosidase gene and
      its association with phenotype in Gaucher disease.
AB  - BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive disorder caused
      mainly by mutations in the glucocerebrosidase (GBA) gene. Great phenotypic
      variability has been observed among patients with the same genotype, suggesting
      other factors, such as polymorphic variants, might influence GD phenotypes. We
      previously reported the c.(-203)A>G (g.1256A>G) variant in exon 1 of the GBA gene
      in Spanish GD patients. METHODS: We analyzed the frequency and transcriptional
      activity of the promoter carrying the G-allele using restriction isotyping,
      electrophoretic mobility shift assay, cell culture, transfection, and luciferase
      assays. RESULTS: We found the variant is present at a similar frequency to the
      control group. In our patients, the G-allele was always found in combination with
      another mutation in the same allele, and patients carrying the c.(-203)A>G
      variant showed a more severe GD phenotype. The promoter containing the G-allele
      showed a 35% reduction in promoter activity when transfected into HepG2 cells.
      CONCLUSION: The c.(-203)A>G variant seems to be a polymorphism resulting in a
      decrease in activity of the GBA promoter. The change, per se, is not enough to
      elicit a GD phenotype, but it may produce a more severe phenotype in GD patients
      when combined with an already defective GBA protein.

PMID- 21087601
TI  - Ectodermal Wnt/beta-catenin signaling shapes the mouse face.
AB  - The canonical Wnt/beta-catenin pathway is an essential component of multiple
      developmental processes. To investigate the role of this pathway in the ectoderm
      during facial morphogenesis, we generated conditional beta-catenin mouse mutants
      using a novel ectoderm-specific Cre recombinase transgenic line. Our results
      demonstrate that ablating or stabilizing beta-catenin in the embryonic ectoderm
      causes dramatic changes in facial morphology. There are accompanying alterations
      in the expression of Fgf8 and Shh, key molecules that establish a signaling
      center critical for facial patterning, the frontonasal ectodermal zone (FEZ).
      These data indicate that Wnt/beta-catenin signaling within the ectoderm is
      critical for facial development and further suggest that this pathway is an
      important mechanism for generating the diverse facial shapes of vertebrates
      during evolution.

PMID- 21087603
TI  - The tumor suppressor protein DLC1 is regulated by PKD-mediated GAP domain
      phosphorylation.
AB  - Deleted in liver cancer 1 (DLC1) is a tumor suppressor protein that is frequently
      downregulated in various tumor types. DLC1 contains a Rho GTPase activating
      protein (GAP) domain that appears to be required for its tumor suppressive
      functions. Little is known about the molecular mechanisms that regulate DLC1. By
      mass spectrometry we have mapped a novel phosphorylation site within the DLC1 GAP
      domain on serine 807. Using a phospho-S807-specific antibody, our results
      identify protein kinase D (PKD) to phosphorylate this site in DLC1 in intact
      cells. Although phosphorylation on serine 807 did not directly impact on in vitro
      GAP activity, a DLC1 serine-to-alanine exchange mutant inhibited colony formation
      more potently than the wild type protein. Our results thus show that PKD-mediated
      phosphorylation of DLC1 on serine 807 negatively regulates DLC1 cellular
      function.

PMID- 21087602
TI  - Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in
      vitro and in vivo.
AB  - Voltage-gated potassium (Kv) channels are widely expressed in the plasma
      membranes of numerous cells and contribute to a variety of cellular functions in
      both excitable neuronal cells and non-excitable epithelial cells. Recently, it
      has been demonstrated that Kv channels are associated with the proliferation of
      several types of cancer cells. In the present study, we investigated the effects
      of suppression of Kv1.3 expression on cell proliferation and cell cycle
      progression in human lung adenocarcinoma, A549 cells. Treatment with margatoxin
      (MgTX), a selective blocker of Kv1.3 or short hairpin RNA (shRNA) against Kv1.3,
      significantly blocked A549 cells' proliferation. In addition, selective
      inhibition of Kv1.3 significantly increased expression level of p21(Waf1/Cip1)
      and significantly decreased the expression level of Cdk4 and cyclin D3. We also
      applied the MgTX into a xenograft model using nude mice, and MgTX caused a
      reduction of tumor volume when it was injected into the tumor tissues. These
      results suggest that Kv1.3 may serve as a novel therapeutic target for lung
      adenocarcinoma therapy.

PMID- 21087604
TI  - Paracrine regulation of growth factor signaling by shed leucine-rich repeats and
      immunoglobulin-like domains 1.
AB  - Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a recently
      discovered negative regulator of growth factor signaling. The LRIG1 integral
      membrane protein has been demonstrated to regulate various oncogenic receptor
      tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR), by
      cell-autonomous mechanisms. Here, we investigated whether LRIG1 ectodomains were
      shed, and if LRIG1 could regulate cell proliferation and EGF signaling in a
      paracrine manner. Cells constitutively shed LRIG1 ectodomains in vitro, and
      shedding was modulated by known regulators of metalloproteases, including the
      ADAM17 specific inhibitor TAPI-2. Furthermore, shedding was enhanced by ectopic
      expression of Adam17. LRIG1 ectodomains appeared to be shed in vivo, as well, as
      demonstrated by immunoblotting of mouse and human tissue lysates. Ectopic
      expression of LRIG1 in lymphocytes suppressed EGF signaling in co-cultured
      fibroblastoid cells, demonstrating that shed LRIG1 ectodomains can function in a
      paracrine fashion. Purified LRIG1 ectodomains suppressed EGF signaling without
      any apparent downregulation of EGFR levels. Taken together, the results show that
      the LRIG1 ectodomain can be proteolytically shed and can function as a non-cell
      autonomous regulator of growth factor signaling. Thus, LRIG1 or its ectodomain
      could have therapeutic potential in the treatment of growth factor receptor
      dependent cancers.

PMID- 21087605
TI  - Let-7b-mediated suppression of basigin expression and metastasis in mouse
      melanoma cells.
AB  - Basigin (Bsg), also called extracellular matrix metalloproteinase inducer
      (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates
      adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps).
      It has been shown that Bsg plays an important role in growth, development, cell
      differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short
      endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as
      post-transcriptional regulators of gene expression by base-pairing to their
      target mRNAs and thereby mediate cleavage of target mRNAs or translational
      repression. In this study, let-7b, one of the let-7 family members, was
      investigated for its effect on the growth and invasiveness of the mouse melanoma
      cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg
      in B16-F10 cells and also provided evidence that this suppression could result in
      the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with
      let-7b to invade or migrate was significantly reduced. In addition, let-7b
      transfected B16-F10 cells displayed an inhibition of both cellular proliferation
      and colony formation. Furthermore, it was shown that the overexpression of let-7b
      in B16-F10 cells could reduce lung metastasis. Taken together, the present study
      identifies let-7b as a tumor suppressor that represses cancer cell proliferation
      and migration as well as tumor metastasis in mouse melanoma cells.

PMID- 21087606
TI  - Intravenous human umbilical cord blood transplantation for stroke: impact on
      infarct volume and caspase-3-dependent cell death in spontaneously hypertensive
      rats.
AB  - Transplantation of human umbilical cord blood cells (HUCBC) produces reliable
      behavioral and morphological improvements in animal models of stroke. However,
      the mechanisms of action still have not been fully elucidated. The aim of the
      present study is the evaluation of potential neuroprotective effects produced by
      HUCBC in terms of reduced infarct volume and caspase-3-dependent cell death.
      Permanent middle cerebral artery occlusion was induced in 90 spontaneously
      hypertensive rats. The animals were randomly assigned to the control group (n=49)
      or the verum group (n=41). The cell suspension (8 * 10(6) HUCBC per kilogram
      bodyweight) or vehicle solution was intravenously administered 24h after stroke
      onset. Fifty subjects (n=25/25) were sacrificed after 25, 48, 72 and 96h, and
      brain specimens were removed for immunohistochemistry for MAP2, cleaved caspase-3
      (casp3) and GFAP. Another 42 animals (n=26/16) were sacrificed after 0, 6, 24, 36
      and 48h and their brains processed for quantitative PCR for casp3 and survivin.
      The infarct volume remained stable over the entire experimental period. However,
      cleaved casp3 activity increased significantly in the infarct border zone within
      the same time frame. Numerous cleaved casp3-positive cells were colocalized with
      the astrocytic marker GFAP, whereas cleavage of neuronal casp3 was observed
      rarely. Neither the infarct volume nor casp3 activity was significantly affected
      by cell transplantation. Delayed systemic transplantation of HUCBC failed to
      produce neuroprotective effects in a permanent stroke model using premorbid
      subjects.

PMID- 21087607
TI  - Postural control in Parkinson patients: a proprioceptive problem?

PMID- 21087608
TI  - Experimentally delayed hatching triggers a magnified stress response in a long
      lived bird.
AB  - In birds, the timing of breeding is a key life-history trait with crucial fitness
      consequences. We predicted that parents may value a brood less if it hatched
      later than expected, thereby decreasing their parental effort. In addition,
      breeding effort would be further modulated by the age-specific decline of future
      breeding opportunities. We experimentally investigated whether snow petrels,
      Pagodroma nivea, were less committed to care for a chick that hatched later than
      expected. The timing of hatching was manipulated by swapping eggs between early
      and late known-age pairs (7-44 years old), and investigations on hormonal and
      behavioral adjustments were conducted. As a hormonal gauge of parental commitment
      to the brood, we measured the corticosterone stress response of guarding adults.
      Indeed, an acute stress response mediates energy allocation towards survival at
      the expense of current reproduction and is magnified when the current brood value
      is low, as it is expected to be in young and/or delayed parents. As predicted,
      egg desertion and the magnitude of the stress response was stronger in delayed
      pairs compared to control ones. However, the treatment did not decrease the
      length of the guarding period, chick condition and chick survival. In addition,
      old parents resisted stress better (lower stress-induced corticosterone levels)
      than young ones. Our study provides evidence that snow petrels, as prudent
      parents, may value a brood less if it hatched later than expected. Thus, in long
      lived birds, the responsiveness to stressors appeared to be adjusted according to
      the individual prospect of future breeding opportunities (age) and to the current
      brood value (timing of breeding).

PMID- 21087609
TI  - Stress effects on AVT and CRF systems in two strains of rainbow trout
      (Oncorhynchus mykiss) divergent in stress responsiveness.
AB  - The aim for this study was to examine whether the F4 generation of two strains of
      rainbow trout divergent in their plasma cortisol response to confinement stress
      (HR: high responder or LR: low responder) would also differ in stress-induced
      effects on forebrain concentrations of mRNA for corticotropin-releasing factor
      (CRF), arginine vasotocin (AVT), CRF receptor type 1 (CRF-R1), CRF receptor type
      2 (CRF-R2) and AVT receptor (AVT-R). In addition, plasma cortisol concentrations,
      brainstem levels of monoamines and monoamine metabolites, and behaviour during
      confinement were monitored. The results confirm that HR and LR trout differ in
      their cortisol response to confinement and show that fish of these strains also
      differ in their behavioural response to confinement. The HR trout displayed
      significantly higher locomotor activity while in confinement than LR trout.
      Moreover, following 180 min of confinement HR fish showed significantly higher
      forebrain concentrations of CRF mRNA than LR fish. Also, when subjected to 30 min
      of confinement HR fish showed significantly lower CRF-R2 mRNA concentrations than
      LR fish, whereas there were no differences in CRF-R1, AVT or AVT-R mRNA
      expression between LR and HR fish either at 30 or 180 min of confinement.
      Differences in the expression of CRF and CRF-R2 mRNA may be related to the
      divergence in stress coping displayed by these rainbow trout strains.

PMID- 21087610
TI  - Does access to the bluestreak cleaner wrasse Labroides dimidiatus affect
      indicators of stress and health in resident reef fishes in the Red Sea?
AB  - Interactions between the bluestreak cleaner wrasse Labroides dimidiatus and its
      client reef fish are a textbook example of interspecific mutualism. The fact that
      clients actively visit cleaners and invite inspection, together with evidence
      that cleaners eat many client ectoparasites per day, indeed strongly suggests a
      mutualistic relationship. What remains unknown is how parasite removal affects
      the physiology of clients and thereby their body condition, health, and immune
      function. Here we addressed these issues in a field study in Ras Mohammed
      National Park, Egypt. In our study area, small reef patches are inter-spaced with
      areas of sandy substrate, thereby preventing many species (i.e., residents,
      including cleaner wrasses) from travelling between the reef patches. This habitat
      structure leads to a mosaic of resident clients with and without access to
      bluestreak cleaner wrasses, further referred to as "cleaner access", on which we
      focused our study. We found that residents with cleaner access had higher body
      condition than residents without cleaner access. However, indicators of stress
      like variation in cortisol levels corrected for handling time and various immune
      parameters were apparently unaffected by cleaner access. In fact antibody
      responses were significantly higher in fishes without cleaner access. This
      suggests that cleaner access decreases the need for active immunity and that this
      releases resources that might be allocated to other functions such as somatic
      growth and reproduction.

PMID- 21087611
TI  - No shot in the dark: myxozoans chemically detect fresh fish.
AB  - This work reports the discovery of an hitherto unknown chemical recognition trait
      enabling a parasitic life cycle in aquatic habitats. We believe this is the first
      record of a natural, host-derived chemical molecule identified as a recognition
      cue for the phylum Myxozoa. The actinospores of these parasites attach to fish
      hosts via polar filaments that are extruded upon mechanical stimulation after
      preceding recognition of a chemical trigger contained in surface mucus. Our goal
      was to identify this signal. We separated compounds from a purified active
      fraction derived from trout mucus by a novel HPLC method. By subsequent nuclear
      magnetic resonance analysis of distinct components and testing in bioassays we
      elicited stimulation of polar filament discharge and sporoplasm emission in
      actinospores of three myxozoan spp., Myxobolus cerebralis, Myxobolus pseudodispar
      and Henneguya nuesslini, by the free nucleosides inosine, 2'-deoxyinosine and
      guanosine. These nucleosides also activated sporoplasm emission. Nucleosides
      appear to be appropriate cues for rapid host recognition by the waterborne
      parasite stages since they are continuously released into surface mucus. The
      recognition mechanism is not specific for susceptible host species, at least in
      the myxozoan spp. examined. In addition, a novel function of nucleobase
      derivatives as semiochemicals was uncovered and a wider impact of this molecule
      class in parasite recognition systems and aquatic chemical ecology is predicted.
      The relevance for disease prevention and cell culturing remains to be explored.

PMID- 21087612
TI  - Recognition of mitochondrial targeting sequences by the import receptors Tom20
      and Tom22.
AB  - The Tom20 and Tom22 receptor subunits of the TOM (translocase of the outer
      mitochondrial membrane) complex recognize N-terminal presequences of proteins
      that are to be imported into the mitochondrion. In plants, Tom20 is C-terminally
      anchored in the mitochondrial membrane, whereas Tom20 is N-terminally anchored in
      animals and fungi. Furthermore, the cytosolic domain of Tom22 in plants is
      smaller than its animal/fungal counterpart and contains fewer acidic residues.
      Here, NMR spectroscopy was used to explore presequence interactions with the
      cytosolic regions of receptors from the plant Arabidopsis thaliana and the fungus
      Saccharomyces cerevisiae (i.e., AtTom20, AtTom22, and ScTom22). It was found that
      AtTom20 possesses a discontinuous bidentate hydrophobic binding site for
      presequences. The presequences on plant mitochondrial proteins comprise two or
      more hydrophobic binding regions to match this bidentate site. NMR data suggested
      that while these presequences bind to ScTom22, they do not bind to AtTom22.
      AtTom22, however, binds to AtTom20 at the same binding site as presequences,
      suggesting that this domain competes with the presequences of imported proteins,
      thereby enabling their progression along the import pathway.

PMID- 21087613
TI  - Synaptotagmin 1 and SNAREs form a complex that is structurally heterogeneous.
AB  - Synaptotagmin 1 (syt1) functions as a Ca(2+)-sensor for neuronal exocytosis.
      Here, site-directed spin labeling was used to examine the complex formed between
      a soluble fragment of syt1, which contains its two C2 domains, and the neuronal
      core soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) complex. Changes in electron paramagnetic resonance lineshape and
      accessibility for spin-labeled syt1 mutants indicate that in solution, the
      assembled core SNARE complex contacts syt1 in several regions. For the C2B
      domain, contact occurs in the polybasic face and sites opposite the Ca(2+)
      binding loops. For the C2A domain, contact is seen with the SNARE complex in a
      region near loop 2. Double electron-electron resonance was used to estimate
      distances between the two C2 domains of syt1. These distances have broad
      distributions in solution, which do not significantly change when syt1 is fully
      associated with the core SNARE complex. The broad distance distributions indicate
      that syt1 is structurally heterogeneous when bound to the SNAREs and does not
      assume a well-defined structure. Simulated annealing using electron paramagnetic
      resonance-derived distance restraints produces a family of syt1 structures where
      the Ca(2+)-binding regions of each domain face in roughly opposite directions.
      The results suggest that when associated with the SNAREs, syt1 is configured to
      bind opposing bilayers, but that the syt1/SNARE complex samples multiple
      conformational states.

PMID- 21087614
TI  - Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded.
AB  - The Wnt pathway tumor-suppressor protein Axin coordinates the formation of a
      critical multiprotein destruction complex that serves to downregulate beta
      catenin protein levels, thereby preventing target gene activation. Given the lack
      of structural information on some of the major functional parts of Axin, it
      remains unresolved how the recruitment and positioning of Wnt pathway kinases,
      such as glycogen synthase kinase 3beta, are coordinated to bring about beta
      catenin phosphorylation. Using various biochemical and biophysical methods, we
      demonstrate here that the central region of Axin that is implicated in binding
      glycogen synthase kinase 3beta and beta-catenin is natively unfolded. Our results
      support a model in which the unfolded nature of these critical scaffolding
      regions in Axin facilitates dynamic interactions with a kinase and its substrate,
      which in turn act upon each other.

PMID- 21087615
TI  - Concerted dynamics link allosteric sites in the PBX homeodomain.
AB  - The PBX1 homeodomain (PBX-HD) cooperatively binds DNA with Hox transcription
      factors and helps to regulate gene expression during vertebrate development.
      Allostery plays an important role in these interactions. DNA binding on one
      surface of PBX-HD enhances interactions with Hox proteins at a different
      interface. In addition, DNA binding causes a 15-residue extension at the C
      terminus of PBX-HD to undergo a disorder-to-helix transition, although this
      region does not directly contact the DNA. Deletion of the C-terminal extension
      reduces both the DNA affinity of PBX-HD and the cooperativity of forming the
      DNA/Hox/PBX-HD ternary complex. To better understand the mechanism underlying
      these allosteric interactions, we used NMR relaxation dispersion dynamics
      experiments to characterize millisecond-timescale motions in PBX-HD over a range
      of temperatures. The data show that the C-terminal extension folds to form a
      fourth alpha-helix to a level of 5-10%, even in the absence of binding partners.
      This suggests that PBX-HD transiently preorganizes prior to binding DNA,
      reminiscent of the "conformational selection" model of molecular recognition.
      Folding of the C-terminal extension in the unbound protein is accompanied by
      structural rearrangements in both the DNA binding site and the Hox binding site,
      suggesting a possible role for these dynamics in the allosteric mechanism of PBX
      HD.

PMID- 21087616
TI  - Specific inhibition of the aspartate aminotransferase of Plasmodium falciparum.
AB  - Aspartate aminotransferases (AspATs; EC 2.6.1.1) catalyze the conversion of
      aspartate and alpha-ketoglutarate into oxaloacetate and glutamate and are key
      enzymes in the nitrogen metabolism of all organisms. Recent findings suggest that
      the plasmodial enzyme [Plasmodium falciparum aspartate aminotransferase
      (PfAspAT)] may also play a pivotal role in energy metabolism and in the de novo
      biosynthesis of pyrimidines. However, while PfAspAT is a potential drug target,
      the high homology between the active sites of currently available AspAT
      structures hinders the development of specific inhibitors of these enzymes. In
      this article, we report the X-ray structure of the PfAspAT homodimer at a
      resolution of 2.8 A. While the overall fold is similar to the currently available
      structures of other AspATs, the structure presented shows a significant
      divergence in the conformation of the N-terminal residues. Deletion of these
      divergent PfAspAT N-terminal residues results in a loss of activity for the
      recombinant protein, and addition of a peptide containing these 13 N-terminal
      residues results in inhibition both in vitro and in a lysate isolated from
      cultured parasites, while the activity of human cytosolic AspAT is unaffected.
      The finding that the divergent N-terminal amino acids of PfAspAT play a role in
      catalytic activity indicates that specific inhibition of the enzyme may provide a
      lead for the development of novel compounds in the treatment of malaria. We also
      report on the localization of PfAspAT to the parasite cytosol and discuss the
      implications of the role of PfAspAT in the supply of malate to the parasite
      mitochondria.

PMID- 21087617
TI  - Development of a variational scheme for model inversion of multi-area model of
      brain. Part II: VBEM method.
AB  - In Part I and Part II of these two companion papers (henceforth called Part I and
      Part II), we develop and evaluate a variational Bayesian expectation maximization
      (VBEM) method for model inversion of our multi-area extended neural mass model
      (MEN). In this paper, we develop the VBEM method to estimate posterior
      distributions of parameters of MEN. We choose suitable prior distributions for
      the model parameters in order to use properties of a conjugate-exponential model
      in implementing VBEM. Consequently, VBEM leads to analytically tractable forms.
      The proposed VBEM algorithm starts with initialization and consists of repeated
      iterations of a variational Bayesian expectation step (VB E-step) and a
      variational Bayesian maximization step (VB M-step). Posterior distributions of
      the model parameters are updated in the VB M-step. Distribution of the hidden
      state is updated in the VB E-step. We develop a variational extended Kalman
      smoother (VEKS) to infer the distribution of the hidden state in the VB E-step
      and derive the forward and backward passes of VEKS, analogous to the Kalman
      smoother. In Part I, we evaluate and validate the VBEM method using simulation
      studies.

PMID- 21087618
TI  - Differential efficiency of simvastatin and lipoic acid treatments on Bothrops
      jararaca envenomation-induced acute kidney injury in mice.
AB  - Snake bite accidents by Bothrops genus is an important public health issue in
      Brazil and one of its most serious complications is the acute kidney injury
      (AKI). Here we evaluated the effects of Bothrops jararaca venom (vBj) and the
      treatments with lipoic acid (LA) and simvastatin (SA) on renal function,
      aminopeptidase (AP) activities and renal redox status. Primordial events for
      establishment of AKI by vBj were hyperuricemia, hypercreatinemia, urinary
      hyperosmolality, renal oxidative stress and reduction of hematocrit and protein
      content in the membrane of renal cortex and medulla and in the plasma. In the
      renal cortex and medulla the changes caused by vBj in soluble and membrane-bound
      AP activities had a similar pattern. The beneficial effects of LA and SA on
      envenomed mice were similar on the hyperuricemia, renal oxidative stress and
      reduction of hematocrit. LA mitigated the hypercreatinemia, but exacerbated the
      urinary urea and creatinine, whereas SA mitigated the decrease of plasma urea,
      urinary hyperosmolality and hypercreatinuria induced by vBj. The beneficial
      effects of LA and especially of SA on renal effects of vBj open a new perspective
      for clinical investigations of these drugs as coadjuvant agents in the
      serotherapy of Bothrops envenomation.

PMID- 21087619
TI  - Clinical and pathological effects of Calotropis procera exposure in sheep and
      rats.
AB  - This study aimed to describe the toxic effects resulting from the administration
      of Calotropis procera (Aiton) W. T. Aiton latex to rats and C. procera leaves to
      sheep. We studied male sheep that received C. procera leaves by gavage. Twenty
      male rats were separated into 5 groups and were subjected to an intra-peritoneal
      injection of fresh C. procera latex (without carrier solvent) at 1.0, 0.6, 0.3 or
      0.1 ml of latex/kg of body weight, and control animals were injected with 0.9%
      NaCl. All rats were treated with the highest dose, but none of the rats from the
      other groups, died. The histological lesions were restricted to rats dosed with
      1.0 ml of latex/kg body weight and included multi-focal coagulation necrosis of
      cardiac fibers and vacuolized hepatocytes. Subsequently, three groups of two
      sheep were treated with (1) a single dose of 30 g/kg, (2) a single dose of 60
      g/kg or (3) 60 g/kg per day for 10 consecutive days. Exposure to the C. procera
      leaves was responsible for tachycardia and transitory cardiac arrhythmias in
      sheep from all groups. Gross pathological analysis of sheep dosed with 60 g/kg
      per day for 10 days revealed mild ascites, exudates on the trachea, pulmonary
      edema, mild hemorrhage in the liver, hydropericardium, flaccid heart, ulcers on
      the abomasum and kidneys presenting pale juxtamedullary cortex. The histological
      findings of the rat and sheep studies were similar and included multi-focal
      coagulation necrosis of cardiac fibers and vacuolized hepatocytes. In conclusion,
      our findings indicate that C. procera is a cardiotoxic and hepatotoxic plant.

PMID- 21087620
TI  - Protection against age-dependent renal injury in the F344xBrown Norway male rat
      is associated with maintained nitric oxide synthase.
AB  - Age-dependent renal damage is influenced by genetic background and the
      Fisher344xBrown Norway (F344xBN) rat is resistant to glomerular injury. In
      vulnerable strains, a fall in renal nitric oxide synthase (NOS) contributes to
      age-dependent renal damage. Here, we investigated renal NOS in young (3 months)
      and old (30 months) male F344xBN to test the hypothesis that renal NOS is
      maintained in "protected" strains. We also examined if 6 months of renin
      angiotensin system (RAS) blockade using angiotensin converting enzyme inhibition
      (ACEI) and angiotensin receptor blockade (ARB) provides further benefit in these
      "protected" old rats. Aging increased tubulointerstitial injury but glomerular
      sclerosis was minimal and NOS and superoxide dismutase abundance increased. There
      was no change in the NOS inhibitor, ADMA (asymmetric dimethylarginine) or its
      regulatory enzymes. RAS blockade with ARB protected against tubulointerstitial
      injury and increased nNOSalpha, but ACEI, which also increased nNOSalpha, had no
      protective effect on the tubulointerstitium. We conclude that the glomerular
      sclerosis-resistant aged male F344xBN rat maintains renal NOS, thus reinforcing
      our hypothesis that progressive glomerular injury is related to renal NOS
      deficiency. The tubulointerstitial injury seen with aging is reversed with 6
      months of ARB but not ACEI and is not associated with renal NOS.

PMID- 21087621
TI  - Antitumor and immunomodulatory activity of arabinoxylans: a major constituent of
      wheat bran.
AB  - We aimed to investigate the antitumor activity of wheat bran arabinoxylans,
      including the role of its immunostimulatory effect. In S180 tumor-bearing mice
      arabinoxylan administration significantly inhibited the growth of mouse
      transplantable tumors and remarkably promoted thymus and spleen indexes,
      splenocyte proliferation, natural killer cell and macrophage phagocytosis
      activity, interleukin 2 production, and delayed-type hypersensitivity reaction.
      In addition, it increased peripheral leukocyte count, and bone-marrow cellularity
      in tumor-bearing mice. As the antitumor activity of arabinoxylans may be mediated
      via the improvement in the immune response, they can be considered an antitumor
      agent with immunomodulatory activity.

PMID- 21087622
TI  - Fructose-induced modifications of myoglobin: Change of structure from met (Fe3+)
      to oxy (Fe2+) form.
AB  - We studied structural modifications of metmyoglobin (Mb) after short-term (6
      days) and long-term (30 days) glycation by fructose (fructation). Fructation
      caused gradual changes in the structure of the protein with respect to increased
      absorbance at 280 nm, enhanced fluorescence emission (with excitation at 285 nm),
      increased surface accessible tryptophan residues and reduced alpha-helix content
      and change in tertiary structure. However, long-term fructation changed Mb to
      oxymyoglobin (MbO2), as demonstrated by different spectroscopic (absorption,
      fluorescence, circular dichroic and electron paramagnetic resonance) studies and
      trifluoperazine-induced oxygen release experiment. Fructation appeared to modify
      Arg139 to arg-pyrimidine, which exhibited antioxidative activity and might be
      involved in the conversion of met (Fe3+) to oxy (Fe2+) form of myoglobin.

PMID- 21087623
TI  - Enzymatic degradation of Antheraea pernyi silk fibroin 3D scaffolds and fibers.
AB  - In this study, the in vitro enzymatic degradation behavior of the regenerated
      Antheraea pernyi silk fibroin (Ap-SF) three-dimensional (3D) scaffolds and the
      natural Ap-SF fibers exposed to enzyme solutions of alpha-chymotrypsin,
      collagenase IA and protease XIV were investigated. The results indicated that all
      three proteases could degrade the Ap-SF 3D scaffolds, and the degradation ability
      was in the order protease XIV>collagenase IA>alpha-chymotrypsin. The regenerated
      Ap-SF 3D scaffold could be degraded completely in 18 days when exposed to 1.0
      U/ml protease XIV at 37 degrees C, whereas under the same condition, the natural
      Ap-SF fiber only lost 5.6% of its weight, revealing its long-term degradation
      characteristics. There were abundant peptides and some free amino acids in the Ap
      SF degradation products, but no free alanine. We suggested that the polyalanine
      block in the regenerated Ap-SF 3D scaffolds had strong resistance to enzyme
      attack. The proteolytic attack occurred in the non-polyalanine block of Ap-SF.
      The degradation rate of Ap-SF materials depended on the molecular conformation of
      Ap-SF, which could be controlled in the manufacturing process.

PMID- 21087624
TI  - Physiological and biochemical consequences of host-plasmid interaction--a case
      study with Corynebacterium renale, a multiple cryptic plasmid containing strain.
AB  - Corynebacterium renale harbors four small cryptic plasmids, pCR1, pCR2, pCR3 and
      pCR4, and can be a good system for understanding host-plasmid interactions. In
      the present study, effect of plasmid loss and their subsequent introduction on
      various properties of the host was evaluated. Loss of plasmids caused a reduction
      in bacterial size and also slowed down their growth rate, MU, and respiratory
      rate, r. Both MU and r values were partially recovered in C. renale R, obtained
      by retransformation of the cured strain with all the four cryptic plasmids.
      Further delineation revealed that a 3153bp plasmid pCR2 alone is sufficient for
      the observed increase in MU in C. renale R. The advantages conferred by the
      remaining three plasmids may be are two subtle to be seen under laboratory
      conditions. Overall, the observations point to the gross metabolic crisis in the
      host partly as a result of loss of plasmids. Based on the findings, a mutualistic
      relationship between the host and the plasmids resulting from their coevolution
      is proposed.

PMID- 21087625
TI  - Construction, modification and evaluation of apolipoprotein A-I promoter-driven
      shRNA expression vectors against hTERT.
AB  - Liver-specific gene knockdown cannot be achieved by short hairpin RNA (shRNA)
      generated by RNA polymerase III promoter. Here we constructed, modified and
      evaluated apolipoprotein A-I (ApoA-I) promoter-driven shRNA expression vectors
      against human telomerase reverse transcriptase (hTERT) in SMMC-7721 cells. The
      roles of the cis-acting hammerhead ribozyme and the specific pausing site MAZ,
      the liver-specific promoter ApoA-I, as well as SV40 and CMV enhancers were first
      individually evaluated, and then they were incorporated to construct a liver
      specific shRNA expression plasmid against hTERT, and the inhibitory effects on
      hTERT were examined in SMMC-7721 cells. The results showed that the introduction
      of the cis-acting hammerhead ribozyme and the specific pausing site MAZ did not
      change gene knockdown efficiency significantly, but eliminated the off-target
      effect. Green fluorescent protein (GFP) expressing plasmid under the control of
      ApoA-I promoter can produce liver-specific GFP expression, but at a much lower
      level compared to the CMV promoter. The CMV or SV40 enhancer-modified ApoA-I
      promoter caused a four or two folds increase in mRNA expression of GFP relative
      to ApoA-I alone, respectively. The liver-specific shRNA expression plasmid
      against hTERT under the control of CMV enhancer-modified ApoA-I promoter with the
      sequences of the cis-acting hammerhead ribozyme and MAZ, induced significant
      inhibitory effect on hTERT at both mRNA and protein levels in SMMC-7721 cells.
      Therefore, liver-specific gene therapy is made possible by utilizing shRNA
      expression vector under the control of CMV enhancer-modified ApoA-I promoter.

PMID- 21087626
TI  - Antibiotic resistant mutants of Escherichia coli K12 show increases in
      heterologous gene expression.
AB  - Using a variety of antibiotics, it was found that nine separate isolates of
      spontaneous antibiotic resistant mutants of Escherichia coli K12 pPSX-vioABCDE
      overproduce the anti-tumour antibiotic violacein. Subsequent analysis showed that
      seven of these mutations occurred on the plasmid pPSX-vioABCDE. The other two
      overproducing strains carried spontaneous chromosomal mutations to lincomycin and
      kanamycin. The kanamycin resistant mutant of E. coli K12 DH10B (AA23) and a
      lincomycin resistant mutant of E. coli K12 LE392 (AA24) increased the synthesis
      of violacein. The plasmid pPSX-vioABCDE opv-1 contains a violacein over
      production (opv-1) mutation which when introduced into either E. coli K12 AA23 or
      AA24, resulted in a hyper-production of violacein. Remarkably, E. coli K12 AA23
      pPSX-vioABCDE opv-1 produced 41 times the normal level of violacein. In addition,
      both E. coli K12 AA23 and E. coli K12 AA24 demonstrated an increase in expression
      of an alpha amylase gene from Streptomyces lividans and the urease gene cluster
      from Klebsiella oxytoca. These results suggest that selection of antibiotic
      resistant mutants can increase heterologous gene expression in E. coli K12.
      Additionally, the increased expression is a general effect applicable to genes
      and gene clusters cloned into E. coli K12 from both Gram-positive and Gram
      negative bacteria.

PMID- 21087627
TI  - Streptomyces turgidiscabies Car8 contains a modular pathogenicity island that
      shares virulence genes with other actinobacterial plant pathogens.
AB  - Streptomyces turgidiscabies Car8 is an actinobacterium that causes the
      economically important disease potato scab. Pathogenesis in this species is
      associated with a mobile pathogenicity island (PAISt) that site specifically
      inserts into the bacA gene in Streptomyces spp. Here we provide the 674,223 bp
      sequence of PAISt, which consists of two non-overlapping modules of 105,364 and
      568,859 bp. These modules are delimited by three copies of an 8 bp palindromic
      sequence (TTCATGAA), that also is the integration site (att) of the element.
      Putative tyrosine recombinase (IntSt) and excisionase (XisSt) proteins are
      encoded just upstream of att-R. PAISt has regions of synteny to pathogenic,
      symbiotic and saprophytic actinomycetes. The 105,364 bp PAISt module is identical
      to a genomic island in Streptomyces scabies 87-22, while the 568,859 bp module
      contains only a short region of synteny to that genome. However, both modules
      contain previously characterized and candidate virulence genes.

PMID- 21087628
TI  - EV71 viral secretion by symptomatic hand foot and mouth disease patients and
      their asymptomatic close contacts.

PMID- 21087629
TI  - Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to
      the C6-peptide in Lyme neuroborreliosis.
AB  - OBJECTIVES: The aim of this study was to evaluate the chemokine CXCL13 and C6
      antibodies separately and in combination in paired serum/cerebrospinal fluid
      (CSF) samples in the laboratory diagnosis of Lyme neuroborreliosis (LNB).
      METHODS: A large retrospective material with paired serum/CSF samples from 261
      patients with clinically suspected LNB was investigated. Patients were divided
      into three main diagnostic groups based on original results of CSF pleocytosis
      and intrathecal anti-borrelia antibodies (purified flagellum). Levels of CXCL13,
      albumin, total IgM and IgG in paired samples and C6 antibodies in CSF were
      compared across diagnostic groups. RESULTS: A sensitivity of 99% and a
      specificity of 96% were achieved for CSF-Serum CXCL13 ratio. CSF-C6 antibodies
      performed with a sensitivity of 99% and a specificity of 88.0%. A combination of
      CSF-Serum CXCL13 ratio and CSF-C6 antibodies, evaluated in parallel, revealed a
      sensitivity of 99% and specificity of 98%. CONCLUSIONS: This study confirms CSF
      CXCL13 as a reliable marker of LNB and suggests improved diagnostic performance
      especially in children with possible LNB.

PMID- 21087630
TI  - Hepatitis A, B, C and HIV infections among Finnish female prisoners--young
      females a risk group.
AB  - OBJECTIVES: Previous prison studies have shown that the female gender is
      associated with higher hepatitis C prevalence. However, there are few prison
      studies of gender differences concerning the risk factors of hepatitis C
      infections. We studied the prevalence of hepatitis and HIV infections and the
      risk factors among Finnish female prisoners. METHODS: The material consisted of
      88 females and 300 male prisoners as controls. RESULTS: The prevalence of
      hepatitis C virus antibodies was 52%, hepatitis B surface antigen 0%, hepatitis A
      virus antibodies 38% and HIV antibodies 1% among women, and 44%, 0.7%, 4% and
      0.7% respectively among men. Among women, 71% of the age group 16-24 had HCV.
      There was no significant association between gender and HCV. Women were more
      commonly sharing syringes/needles and had unsafe sexual habits. Among women, HCV
      was associated only with IDU and syringe/needle sharing whereas among men also
      with tattoos, cumulative years in prison and age. CONCLUSIONS: Especially young
      females had a high prevalence of HCV. The study showed that the risk factors are
      differentiated by gender. This should be taken into account when assessing
      earlier studies which mainly concentrate on men.

PMID- 21087631
TI  - In honour of Gaosheng Huang on the occasion of his 65th birthday.

PMID- 21087633
TI  - Feasibility of using an artificial neural network model to estimate the elbow
      flexion force from mechanomyography.
AB  - The goal of this study was to demonstrate the feasibility of using artificial
      neural network (ANN) models to estimate the elbow flexion forces from
      mechanomyography (MMG) under isometric muscle contraction and compare the
      performance of the ANN models with the performance from multiple linear
      regression (MLR) models. Five participants (mean+/-SD age=25.4+/-2.96 yrs)
      performed ten predefined and ten randomly ordered elbow flexions from 0% to 80%
      maximal voluntary contractions (MVCs). The MMG signals were recorded from the
      biceps brachii (BR) and brachioradialis (BRD), both of which contribute to elbow
      flexion. Inputs into the model included the root-mean-square (RMS), a temporal
      characterization feature, which resulted in a slightly higher signal-to-noise
      ratio (SNR) than when using the mean absolute value (MAV), and the zero-crossing
      (ZC) as spectral characterization features. Additionally, how the RMS and the ZC
      as model inputs affected the estimation accuracy was investigated. A cross
      subject validation test was performed to determine if the established model of
      one subject could be applied to another subject. It was observed that the ANN
      model provided a more accurate estimation based on the values of the normalized
      root mean square error (NRMSE=0.141+/-0.023) and the cross-correlation
      coefficient (CORR=0.883+/-0.030) than the estimations from the MLR model
      (NRMSE=0.164+/-0.030, CORR=0.846+/-0.033). The estimation results from the same
      subject validation test were significantly better than those of the cross-subject
      validation test. Thus, using an ANN model on a subject-by-subject basis to
      quantify and track changes in the temporal and spectral responses of MMG signals
      to estimate the elbow flexion force is a reliable method.

PMID- 21087634
TI  - Optimization of a contextual conditioning protocol for rats using combined
      measurements of startle amplitude and freezing: the effects of shock intensity
      and different types of conditioning.
AB  - Contextual conditioning in rats is typically quantified using startle amplitude
      or freezing time. Our goal was to create a robust contextual conditioning
      protocol combining both startle amplitude and freezing time as measures of
      contextual anxiety. Comparison of 0.8 mA - 250 ms shocks with an established
      shock configuration (0.3 mA - 1 s) favoured the first parameters. Subsequently,
      we systematically investigated the effect of shock intensity (0.6 mA, 0.8 mA or
      1.0 mA) and concurrently compared two different contextual conditioning
      procedures (shocks alone versus unpaired shock-tone presentations). In future
      experiments, this second type of contextual conditioning may form the optimal
      contrasting condition for a cued fear conditioning group, trained with explicit
      cue-shock pairings. The 0.8 mA shocks produced significant contextual freezing
      and startle potentiation, whereas the 0.6 mA and 1.0 mA shocks only led to a
      significant increase of freezing time. We found no major differences between the
      two types of conditioning, implying that these procedures might be equivalent. In
      conclusion, training with ten 0.8 mA - 250 ms shocks produced reliable contextual
      conditioning as measured with both startle amplitude and freezing time.

PMID- 21087635
TI  - A multi-slice recording system for stable late phase hippocampal long-term
      potentiation experiments.
AB  - A major challenge in neuroscience is identifying the cellular and molecular
      processes underlying learning and memory formation. In the past decades,
      significant progress has been made in understanding cellular and synaptic
      mechanisms underlying hippocampal learning and memory using long-term
      potentiation (LTP) experiments in brain slices as a model system. To expedite LTP
      measurements it is helpful to further optimize such recording systems. Here, we
      describe a modification of a multi-slice recording system (SliceMaster,
      Scientifica Limited, East Sussex, UK) that allows absolutely stable measurements
      of field excitatory postsynaptic potentials (fEPSPs) for up to 8 h in up to eight
      slices simultaneously. The software Notocord((r)) was used for on-line data
      acquisition and to control the digital pattern generator which can generate
      different patterns for slice stimulation, inducing different types of LTP.
      Moreover, in contrast to common gravity-driven perfusion systems, a Pumped
      Perfusion System was employed to recycle drug solutions applied to the
      hippocampal slice. In addition, slices were positioned on two stacked grids for
      optimal recording of fEPSPs. These two stacked grids were placed in the measuring
      chambers allowing recordings for several hours without any perturbances. In
      summary, this modified slice-recording system improves throughput and allows for
      better statistical design, increases number of used slices per animal and enables
      very robust LTP measurements for up to 7 h. Hence, this system is suitable not
      only to investigate molecular mechanisms underlying the late phase of LTP, but
      also to screen candidate compounds in the context of drug discovery.

PMID- 21087632
TI  - Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of
      cellular fat stores.
AB  - Lipolysis is the biochemical pathway responsible for the catabolism of
      triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage
      of TAG generates non-esterified fatty acids, which are subsequently used as
      energy substrates, essential precursors for lipid and membrane synthesis, or
      mediators in cell signaling processes. Consistent with its central importance in
      lipid and energy homeostasis, lipolysis occurs in essentially all tissues and
      cell types, it is most abundant, however, in white and brown adipose tissue. Over
      the last 5years, important enzymes and regulatory protein factors involved in
      lipolysis have been identified. These include an essential TAG hydrolase named
      adipose triglyceride lipase (ATGL) [annotated as patatin-like phospholipase
      domain-containing protein A2], the ATGL activator comparative gene identification
      58 [annotated as alpha/beta hydrolase containing protein 5], and the ATGL
      inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive
      lipase [annotated as lipase E] and monoglyceride lipase, these proteins
      constitute the basic "lipolytic machinery". Additionally, a large number of
      hormonal signaling pathways and lipid droplet-associated protein factors regulate
      substrate access and the activity of the "lipolysome". This review summarizes the
      current knowledge concerning the enzymes and regulatory processes governing
      lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will
      be given to ATGL, its regulation, and physiological function.

PMID- 21087636
TI  - Twenty-four mini-pool HCV RNA screening in a routine clinical virology laboratory
      setting: a six-year prospective study.
AB  - The usefulness of combined anti-HCV and 24 mini-pool HCV RNA screening strategy
      was re-evaluated after a six-year continuous routine use in a clinical virology
      laboratory, at which more than half of newly diagnosed hepatitis C patients are
      intravenous drug users. Pools of 24 samples were prepared from 20,448 anti-HCV
      negative serum samples and tested using an automated commercial PCR assay with a
      lower limit of detection of 50 IU/ml. After detection of anti-HCV negative/HCV
      RNA positive patients, responsible physicians provided follow-up samples. Thirty
      eight (0.19%) anti-HCV negative/HCV RNA positive samples from 30 patients (28
      intravenous drug users) were detected. Follow-up samples were available for 27/30
      patients. Twenty, six and one patient seroconverted in the second, third and
      fourth available samples, respectively. The interval between the first HCV RNA
      positive and the first available anti-HCV positive sample was 17-517 days. The
      costs of detecting a single anti-HCV negative/HCV RNA positive patient were 1227
      Euros. Combined anti-HCV and 24 mini-pool HCV RNA screening is a useful and cost
      effective strategy, not only in blood-transfusion settings but also in a routine
      clinical virology laboratory, at which a significant proportion of the tested
      population belongs to a high-risk population.

PMID- 21087637
TI  - Validation of commercial real-time RT-PCR kits for detection of influenza A
      viruses in porcine samples and differentiation of pandemic (H1N1) 2009 virus in
      pigs.
AB  - Swine influenza, apart from its importance in animal health, may also be of
      public health significance. Although the first human infections with the multi
      reassortant H1N1 virus (pH1N1/09) responsible for the 2009 pandemic were not
      related to pig exposure, this virus was shown to be related genetically to swine
      influenza viruses (SIV) and easily transmissible to pigs. In addition to direct
      animal health concerns, transmission and possible adaptation of the pH1N1/09
      virus in pigs may have serious consequences on the risk of human infection by
      increasing the reservoir of this virus and the risk of possible emergence of new
      reassortant viruses with increased virulence for pigs and/or humans. Sensitive
      tools to monitor and detect rapidly such an infection are therefore mandatory. In
      this study, five commercial real-time RT-PCR assays developed by manufacturers
      LSI and Adiagene were assessed and validated, (i) for rapid detection of
      influenza A viruses, including pH1N1/09, in pig and (ii) for the differentiation
      of pH1N1/09 in that species. Two kits target the influenza A virus M gene, two
      others amplify the pH1N1/09 virus H1 gene and one kit targets the pH1N1/09 virus
      N1 gene. All five kits are ready-to-use, one-step duplex RT-PCR and contain an
      internal positive control (IPC), appropriate for porcine biological samples, for
      assessing RNA extraction efficiency and the presence of PCR inhibitors. They have
      been used successfully by veterinary laboratories and shown to be powerful tools
      for the diagnosis and epidemiological surveillance of influenza virus infections
      in pigs.

PMID- 21087638
TI  - Development of a dot immunoblot method for differentiation of animals infected
      with foot-and-mouth disease virus from vaccinated animals using non-structural
      proteins expressed prokaryotically.
AB  - Five non-structural proteins (NSPs) of foot-and-mouth disease virus (FMDV) were
      expressed in E. coli to develop a dot immunoblot (dot blot) assay for the
      differentiation of FMDV infected animals from vaccinated animals (DIVA). The five
      NSPs were 3A (24 kDa), 3B (15 kDa), major B-cell epitope regions of 2C (23 kDa),
      partial 3D (44 kDa) and 3ABC (59 kDa). The criteria for the dot blot were
      determined and are described as follows: a test sample is considered positive if
      four or more NSPs demonstrate staining densities equal to or higher than those of
      their appropriate controls; a sample is considered negative if two or more
      antigens demonstrate densities below their negative control. A specificity of
      100% was observed based on testing of sera from clinical healthy animals with or
      without vaccination; the sensitivity of the dot blot was 96.1% and 65.8% for
      testing of samples from infected cattle and swine, respectively, at an early
      stage of the infection. Meanwhile, high rates of concordance were observed
      between the dot blot and the PrioCHECK(r) FMDV-NS test. The dot blot has the
      potential to act as a confirmatory method for DIVA by 3ABC-ELISA.

PMID- 21087639
TI  - Quantitation of ranaviruses in cell culture and tissue samples.
AB  - A quantitative real-time PCR (qPCR) based on a standard curve was developed for
      detection and quantitation of ranaviruses. The target gene for the qPCR was viral
      DNA polymerase (DNApol). All ten ranavirus isolates studied (Epizootic
      haematopoietic necrosis virus, EHNV; European catfish virus, ECV; European
      sheatfish virus, ESV; Frog virus 3, FV3; Bohle iridovirus, BIV; Doctor fish
      virus, DFV; Guppy virus 6, GV6; Pike-perch iridovirus, PPIV; Rana esculenta virus
      Italy 282/I02, REV282/I02 and Short-finned eel ranavirus, SERV) were detected
      with the qPCR assay. In addition, two fish cell lines - epithelioma papulosum
      cyprini (EPC) and bluegill fry (BF-2) - were infected with four of the isolates
      (EHNV, ECV, FV3 and DFV), and the viral quantity was determined from seven time
      points during the first three days after infection. The qPCR was also used to
      determine the viral load in tissue samples from pike (Esox lucius) fry challenged
      experimentally with EHNV.

PMID- 21087640
TI  - Replication of biotinylated human immunodeficiency viruses.
AB  - Previous work demonstrated recently the adaptation of the Escherichia coli biotin
      ligase BirA - biotin acceptor sequence (BAS) labeling system to produce human
      immunodeficiency virus type 1 viruses with biotinylated integrase (NLXIN(B)) and
      matrix (NLXMA(B)) proteins (Belshan et al., 2009). This report describes the
      construction of an HIV permissive cell line stably expressing BirA (SupT1.BirA).
      Consistent with the results in the previous report, NLXMA(B) replicated similar
      to wild-type levels and expressed biotinylated Gag and MA proteins in the
      SupT1.BirA cells, whereas the replication of NLXIN(B) was reduced severely. Three
      additional HIV type 2 (HIV-2) viruses were constructed with the BAS inserted into
      the vpx and vpr accessory genes. Two BAS insertions were made into the C-terminal
      half of the Vpx, including one internal insertion, and one at the N-terminus of
      Vpr. All three viruses were replication competent in the SupT1.BirA cells and
      their target proteins biotinylated efficiently and incorporated into virions.
      These results demonstrate the potential utility of the biotinylation system to
      label and capture HIV protein complexes in the context of replicating virus.

PMID- 21087641
TI  - Differential activation of mitogen-activated protein kinases and glial cells in
      the trigeminal sensory nuclear complex following lingual nerve injury.
AB  - Mitogen-activated protein kinases (MAPKs) play a pivotal role in the mediation of
      cellular responses to a variety of signaling molecules. The current study
      demonstrates phosphorylation of extracellular signal-regulated kinase (ERK) and
      p38 MAPK in each subdivision of the trigeminal sensory nuclear complex (TSNC)
      following lingual nerve injury. Immunohistochemical labeling for phosphorylated
      ERK (p-ERK) or phosphorylated p38 (p-p38) MAPK was performed in histological
      sections of the brainstem. A transient increase in the immunoreactivity for p-ERK
      was found in each subdivision of the TSNC followed by a prolonged increase in the
      immunoreactivity for p-p38 MAPK after nerve injury. Double immunofluorescence
      labeling with cell-specific markers revealed that ERK and p38 MAPK were
      phosphorylated predominantly by OX-42-positive microglia or GFAP-positive
      astrocytes. Increased immunofluorescence labeling for OX-42 and GFAP indicated
      that microglia and astrocytes were activated by nerve injury in the TSNC.
      Activation of MAPKs and glial cells in the rostral subdivisions of the TSNC was
      comparable with that in the subnucleus caudalis of the trigeminal spinal tract
      nucleus (Vc). We conclude that differential activation of MAPKs and glial cells
      in the rostral subdivisions of the TSNC as well as the Vc may have a substantial
      role in the pathogenesis of neuropathic pain following trigeminal nerve injury.

PMID- 21087642
TI  - Effect of protein structural integrity on cross-linking by tyrosinase evidenced
      by multidimensional heteronuclear magnetic resonance spectroscopy.
AB  - Enzymatic cross-linking of proteins can be catalyzed either by transferase-type
      enzymes, e.g., transglutaminases, or by oxidoreductases, e.g., tyrosinases or
      laccases. Three-dimensional structure of protein substrate plays a key role in
      these reactions, that is, the reactivity and end product are strongly modulated
      by the accessibility of target amino acid residues to the cross-linking enzyme.
      Typically structural integrity of protein can be distorted by heat, pH, or
      mechanical action, as well as by varying ionic concentration of the solution. In
      this study we used partially unfolded protein (wild-type DrkN SH3) and its
      structurally stabilized mutant (T22G) to investigate the impact of
      folded/unfolded conformations on cross-linking by Trichoderma reesei tyrosinase.
      Our results clearly showed formation of intermolecular cross-links solely between
      unfolded conformations, making them superior substrates to folded proteins when
      using tyrosinase as a cross-linking enzyme. Multidimensional heteronuclear
      magnetic resonance experiments in solution state were employed to investigate
      cross-linked end-products. The results presented in this study form basis for
      application development in food, medical, cosmetic, textile, packing and other
      sectors. In addition, the outcome of this study has a high value for the basic
      understanding of reaction mechanism of tyrosinases on proteins.

PMID- 21087643
TI  - RhizoRegNet--a database of rhizobial transcription factors and regulatory
      networks.
AB  - Sinorhizobium meliloti is a symbiotic soil bacterium that forms nitrogen-fixing
      nodules on roots of leguminous plants, including Medicago truncatula (barrel
      medic), and M. sativa (alfalfa). The Sinorhizobium-Medicago symbiosis is an
      important symbiosis model system. Knowledge gained from this system can be
      extended to other agriculturally important "rhizobial" symbioses. Since the
      publication of the S. meliloti genome in 2001, many new genetic, biochemical and
      physiological data have been generated. Effective methods to organize, store, and
      mine this postgenome data are crucial for continued success of the S. meliloti
      model system. In 2009, we introduced a portal for rhizobial genomes, RhizoGATE
      (Becker et al., J. Biotechnol. 140, 45-50). The RhizoGATE portal combines
      continuously updated S. meliloti genome annotation with postgenome data
      resources. Here we report integration of a new component, RhizoRegNet, to
      RhizoGATE. RhizoRegNet combines transcriptome data and operon predictions with
      published data on regulatory interactions. By allowing searching and
      visualisation of complex transcriptional regulatory networks, RhizoRegNet
      advances our understanding of transcriptional regulation in S. meliloti. The
      current version of RhizoRegNet is divided into 13 functional modules containing
      information for 114 regulators, 475 regulated genes, and 178 transcription factor
      binding motifs. In this report, we provide an example of how RhizoRegNet
      facilitates visualisation and analysis of the regulatory network for
      exopolysaccharide biosynthesis and motility. Presently, RhizoRegNet contains
      regulatory network information for S. meliloti and the closely related bacterium,
      S. medicae, but can be expanded to include other rhizobial species.

PMID- 21087644
TI  - Gene delivery to human bone marrow mesenchymal stem cells by microporation.
AB  - Electroporation has been considered one of the most efficient non-viral based
      methods to deliver genes regardless of frequently observed high cell mortality.
      In this study we used a microporation technique to optimise the delivery of
      plasmid DNA encoding green fluorescence protein (GFP) to human bone marrow
      mesenchymal stem cells (BM-MSC). Using resuspension buffer (RB) and as low as 1.5
      x 105 cells and 1 MUg of DNA, we achieved 40% of cells expressing the transgene,
      with cell recovery and cell viabilities of 85% and 90%, respectively. An increase
      in DNA amount did not significantly increase the number of transfected cells but
      clearly reduced cell recovery. A face-centered composite design was used to
      unveil the conditions giving rise to optimal plasmid delivery efficiencies when
      using a sucrose based microporation buffer (SBB). The BM-MSC proliferation
      kinetics were mainly affected by the presence of plasmid and not due to the
      microporation process itself although no effect was observed on their
      immunophenotypic characteristics and differentiative potential. Based on the data
      shown herein microporation demonstrated to be a reliable and efficient method to
      genetically modify hard-to-transfect cells giving rise to the highest levels of
      cell survival reported so far along with superior gene delivery efficiencies.

PMID- 21087645
TI  - Selective follicular targeting by modification of the particle sizes.
AB  - Hair follicles represent interesting target sites for topically applied
      substances such as topical vaccinations or agents used in the field of
      regenerative medicine. In recent years, it could be shown that particles
      penetrate very effectively into the hair follicles. In the present study, the
      influence of particle size on the follicular penetration depths was examined. The
      penetration depths of two different types of particles sized 122 to 1000 nm were
      determined in vitro on porcine skin. The results revealed that the particles of
      medium size (643 and 646 nm, respectively) penetrated deeper into the porcine
      hair follicles than smaller or larger particles. It was concluded that by varying
      the particle size, different sites within the porcine hair follicle can be
      targeted selectively. For the human terminal hair follicle, the situation can be
      expected to be similar due to a similar size ratio of the hair follicles.

PMID- 21087646
TI  - Comparison of five different targeting ligands to enhance accumulation of
      liposomes into the brain.
AB  - In many different studies nanocarriers modified with targeting ligands have been
      used to target to the brain. Many ligands have been successful, but it is
      difficult to compare results from different studies to determine which targeting
      ligand is the best. Therefore, we selected five targeting ligands (transferrin,
      RI7217, COG133, angiopep-2, and CRM197) and compared their ability to target
      liposomes to the brain in vitro and in vivo. In vitro, only CRM197-modified
      liposomes were able to bind to murine endothelial cells (bEnd.3). Both CRM197 and
      RI7217-modified liposomes associated with human endothelial cells (hCMEC/D3). In
      vivo, uptake of targeted liposomes was tested at 12h after iv injection. For some
      of the ligands, additional time points of 1 and 6h were tested. Only the RI7217
      was able to significantly enhance brain uptake in vivo at all time points. Uptake
      in the brain capillaries was up to 10 times higher compared to untargeted
      liposomes, and uptake in the brain parenchyma was up to 4.3 times higher.
      Additionally, these results show that many targeting ligands that have been
      described for brain targeting, do not target to the brain in vivo when coupled to
      a liposomal delivery vehicle.

PMID- 21087647
TI  - Peptidomic analysis of skin secretions from the bullfrog Lithobates catesbeianus
      (Ranidae) identifies multiple peptides with potent insulin-releasing activity.
AB  - Using a combination of reversed-phase HPLC and electrospray mass spectrometry,
      peptidomic analysis of norepinephrine-stimulated skin secretions of the American
      bullfrog Lithobates catesbeianus Shaw, 1802 led to the identification and
      characterization of five newly described peptides (ranatuerin-1CBb, ranatuerin
      2CBc, and -CBd, palustrin-2CBa, and temporin-CBf) together with seven peptides
      previously isolated on the basis of their antimicrobial activity (ranatuerin
      1CBa, ranatuerin-2CBa, brevinin-1CBa, and -1CBb, temporin-CBa, -CBb, and -CBd).
      The abilities of the most abundant of the purified peptides to stimulate the
      release of insulin from the rat BRIN-BD11 clonal beta cell line were evaluated.
      Ranatuerin-2CBd (GFLDIIKNLGKTFAGHMLDKIRCTIGTCPPSP) was the most potent peptide
      producing a significant stimulation of insulin release (119% of basal rate,
      P<0.01) from BRIN-BD11 cells at a concentration of 30nM, with a maximum response
      (236% of basal rate, P<0.001) at a concentration of 3MUM. Ranatuerin-2CBd did not
      stimulate release of the cytosolic enzyme, lactate dehydrogenase at
      concentrations up to 3MUM, indicating that the integrity of the plasma membrane
      had been preserved. Brevinin-1CBb (FLPFIARLAAKVFPSIICSVTKKC) produced the maximum
      stimulation of insulin release (285% of basal rate, P<0.001 at 3MUM) but the
      peptide was cytotoxic at this concentration.

PMID- 21087648
TI  - Induction of cell surface human leukocyte antigen-G expression in pandemic H1N1
      2009 and seasonal H1N1 influenza virus-infected patients.
AB  - A novel H1N1 virus of swine origin (H1N1v) recently caused a pandemic; however,
      knowledge of immunologic aspects of the virus infection are limited. Human
      leukocyte antigen-G (HLA-G) was speculated to play critical roles in viral
      infection, although its clinical relevance in H1N1 infection remains unknown. In
      this study, HLA-G expression in peripheral T lymphocytes, monocytes, and CD4(+)
      CD25(+) FoxP3+ regulatory T (Treg) cells (in 50 H1N1v-infected and 41 seasonal
      H1N1-infected patients and 27 control subjects) were analyzed by flow cytometry.
      Plasma-soluble HLA-G (sHLA-G, in 28 H1N1v-infected, 29 seasonal H1N1-infected
      patients and 85 control subjects) were determined with enzyme-linked
      immunosorbent assay. The percentage of HLA-G-positive T lymphocytes and monocytes
      among patients with H1N1v and seasonal H1N1 infections was dramatically increased
      compared with controls (all p < 0.001). Treg was markedly increased among H1N1v-
      infected patients compared with normal controls (p = 0.041), but not for the
      seasonal H1N1-infected patients. Meanwhile, no significant difference was
      observed for sHLA-G levels between the groups. Together, cell surface HLA-G
      expression was markedly induced in H1N1v-infected and seasonal H1N1-infected
      patients, and increased Treg was observed only in H1N1v-infected patients. Given
      its immune-suppressive property, elevated cell surface HLA-G expression may help
      to explain the virus escaping from host immune responses.

PMID- 21087649
TI  - Psychopharmacological comparison of schizophrenia spectrum disorder with and
      without cannabis dependency.
AB  - BACKGROUND: Although incidence of schizophrenia is higher among cannabis users
      and marijuana is the most common abused drug by adolescents, etiological linkage
      between schizophrenia and cannabis use is still not clarified. Clinical
      experiences suggest that regular cannabis user can show similar psychotic episode
      to schizophrenic disorders but it is still unclear if chronic cannabis use with
      schizophreniform disorder is a distinct entity requiring special therapy or it
      can be treated as classical schizophrenia. There are no data available on the
      comparison of pharmacotherapy between schizophreniform patients with and without
      cannabis use. METHODS: Clinical data of 85 patients with schizophrenia spectrum
      disorder were analyzed retrospectively. Cannabis use was not reported by 43
      persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least
      1 year (Cnbs1 subgroup). Comparison of anamnesis, family history, social
      demographic condition, positive and negative symptoms, acute and long-term
      therapies recorded by clinical interviews was performed with chi square tests,
      logistic binary regression and t-tests using SPSS 13.0 for Windows software.
      RESULTS: Men were over-represented in cannabis dependent group while mean age was
      lower among them compared to Cnbs0 subgroup. Prevalence of suicidal attempt was
      increased in men without cannabis use (OR = 5.25, p = 0.016). Patients without
      cannabis use spent more time in hospital (p = 0.026) and smoking was more
      frequent among them (OR = 1.36, p = 0.047). The chance to get olanzapine for
      acute therapy and aripiprazol for long term therapy was more than two fold in
      Cnbs1 subgroup (OR = 2.66, OR = 3.67, respectively). However, aripiprazol was
      used for acute therapy with significantly lower risk in Cnbs1 subgroup (OR =
      0.47, p = 0.023). Olanzapine was administered for long term therapy in a higher
      dose to Cnbs0 patients (p = 0.040). Also higher dose of risperidon LAI was used
      in women without cannabis dependency compared to women of Cnbs1 subgroup
      (p=0.020). Positive and negative symptoms and family history did not differ
      significantly between the two subgroups. CONCLUSION: Although symptom profile was
      similar, hospitalization time, suicidal anamnesis, smoking habit and also dosage,
      intensity and lasting of therapy were different between the two subgroups.
      Further prospective studies are required for the investigation of the clinical
      and molecular background of this discrepancy in order to determine a relevant
      protocol of prevention and treatment of the chronic cannabis use related
      psychotic disorder.

PMID- 21087650
TI  - Genotoxic and apoptotic activities of the food flavourings myristicin and eugenol
      in AA8 and XRCC1 deficient EM9 cells.
AB  - Some food flavourings, such as safrole and methyleugenol, are known for their
      genotoxic and hepatocarcinogenic properties whereas for others, such as
      myristicin, there is less data. Myristicin and eugenol are both alkenylbenzenes,
      and we compared their direct genotoxicity in repair proficient (AA8) and repair
      deficient XRCC(-) (EM9) Chinese hamster ovary cells. Cell viability was assessed
      by the MTT assay. The comet assay was used to evaluate DNA breaks, and the gamma
      H2AX assay to evaluate induction of double strand breaks. We assessed apoptosis
      by measuring caspases activation, and the TUNEL assay. Reduction of cell
      viability was similar in AA8 and EM9 cells, for both compounds. After 1h eugenol
      produced DNA strand breaks in the comet assay and induced double strand breaks in
      the gamma-H2AX assay in AA8 cells, while myristicin was not genotoxic in both the
      comet and the gamma-H2AX assays. Both flavourings were negative in EM9 cells.
      After 24h eugenol and myristicin induced DNA fragmentation detected by TUNEL in
      both cell lines, but only myristicin activated caspases. Myristicin was more
      apoptotic than eugenol, in both cell lines. The XRCC1 protein does not influence
      the apoptotic activity of either compound.

PMID- 21087651
TI  - Mission impossible? Regulatory and enforcement issues to ensure safety of dietary
      supplements.
AB  - Dietary supplements are widely used across all ages and user groups and
      constitute a considerable business sector in most developed countries. Hazards
      relating to concentration, composition, individual contaminants and supplement
      interactions present an increasing public health concern. The aim of this paper
      is to review the literature for reported supplement contaminations (occurs in ca
      25% of supplements, with anabolic steroids being the most common) and complement
      these findings with notifications logged in the EU's Rapid Alert System for Food
      and Feed (RASFF) through imports or market surveillance, typically logged for
      poor quality control issues. Notifications in the RASFF have steadily increased
      by sixfold for supplements in the past 7 years with the USA and China being the
      major transgressors. Finland and Italy lead in detections, mainly notifying
      unpermitted substances and contaminants in sexual-enhancing or weight-loss
      supplements. This paper highlights the paucity of enforcement. Regulating
      supplements as a foodstuff and not a medicine, coupled with the fact that a
      significant proportion of the supplement market is distributed via the Internet
      (hence absent from routine border control and surveillance), make ensuring and
      enforcing safety a very challenging task. The need for better quality control,
      compliance and public awareness is evident.

PMID- 21087652
TI  - Transient neutropenia after granulocyte-colony stimulating factor administration
      is associated with neutrophil accumulation in pulmonary vasculature.
AB  - OBJECTIVE: To better define the nature of the transient neutropenia shortly
      following granulocyte-colony stimulating factor (G-CSF) administration. MATERIALS
      AND METHODS: To evaluate the disappearance of neutrophils, we investigated
      neutrophil trafficking. Ratios of neutrophil number to background cellularity for
      C57BL/6 LysM-EGFP knock-in mice and rhesus macaques were determined in the lung,
      liver, spleen, and kidney after G-CSF administration. RESULTS: For the C57BL/6
      LysM-EGFP knock-in mice, the enhanced green fluorescent protein expression
      (EGFP(+)) cells increased in the lung and spleen within 15 minutes of
      administering 50 MUg/kg G-CSF subcutaneously, and continued to increase in the
      lung and spleen from 15 minutes to 30 minutes. At 240 minutes, the pulmonary
      infiltrate declined to a level comparable to the level at 15 minutes, while in
      the spleen EGFP(+) cells continued to increase. For rhesus macaques, CD18(+)
      cells also significantly increased in the lung 30 minutes after administration of
      10 MUg/kg G-CSF subcutaneously compared to the control level. CONCLUSIONS: These
      results suggest that the transient neutropenia following G-CSF administration in
      the mouse and nonhuman primate is associated with an accumulation of neutrophils
      within pulmonary and splenic vasculature.

PMID- 21087653
TI  - Differential survival of AML subpopulations in NOD/SCID mice.
AB  - OBJECTIVE: Leukemia-initiating cells can retrospectively be defined by
      tumorigenicity in immunodeficient mice and be characterized by surface markers.
      The latter still being discussed for acute myeloid leukemia (AML), nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice were used to evaluate
      long-time reconstitution and expansion of AML subpopulations. MATERIALS AND
      METHODS: Bone marrow cells from patients with AML were separated according to
      CD34 expression, aldehyde dehydrogenase (ALDH) activity, and divisional kinetics
      in comparison to cord blood-derived CD34(+) hematopoietic stem cells, evaluating
      survival and expansion in NOD/SCID mice. The AML long-term surviving capacity of
      subpopulations recovered from NOD/SCID mice was confirmed by ex vivo survival.
      RESULTS: AML mononuclear cells were detected in bone marrow and spleen of
      NOD/SCID mice 12 weeks after transplantation. The majority of recovered cells
      were CD34(+) and significantly more CD34(+) cells were recovered after
      application of ALDH(bright) (high ALDH activity), CD34(+), or slowly dividing
      (PKH(bright)) than after ALDH(dim), CD34(-), or fast dividing (PKH(dim)) cell
      application. CD123(+), CD63(+), and CD44v7(+) cells were also more abundant after
      the transfer of ALDH(bright) or CD34(+) AML mononuclear cells. In the spleen,
      large AML cell clusters were only recovered after ALDH(bright), CD34(+), or
      PKH(bright) cell transfer. Importantly, in secondary long-term in vitro cultures,
      quite exclusively CD34(+) AML mononuclear cells survived and expanded.
      CONCLUSIONS: Separation of ALDH(bright), CD34(+), or PKH(bright) cells enriches
      for AML long-term surviving capacity, which reside in the CD34(+) subpopulation,
      as rather exclusively CD34(+) cells survived and expanded in vivo and ex vivo.
      Long-term survival capacity may be supported by CD44v7 expression.

PMID- 21087654
TI  - Kv7 (KCNQ) channel openers induce hypothermia in the mouse.
AB  - Kv7 channels, encoded by corresponding kcnq genes, are expressed both centrally
      and peripherally where they serve to dampen neuronal activity. While Kv7 channel
      openers have shown efficacy in neurological and neuropsychiatric disease models,
      the impact of Kv7 channel activation on physiological endpoint markers have not
      been addressed in detail. In this study we assessed the effect of a range of Kv7
      channel openers with different affinity for neuronal Kv7.2-5 channel subunits on
      body temperature regulation in mice. Female NMRI mice were acutely exposed to
      vehicle (10% Tween-80, i.p.), retigabine (3-30 mg/kg, i.p., pan-Kv7 channel
      opener), (S)BMS-204352 (60-240 mg/kg, i.p., Kv7.4/5 channel-preferring opener),
      ICA-27243 (1-10mg/kg, i.p., Kv7.2/3 channel-preferring opener), or S-(1) (10-60
      mg/kg, i.p., Kv7.2/3 channel-preferring opener), and rectal body temperature was
      measured 15-120 min post-injection. Retigabine (>10mg/kg), ICA-27243 (>= 10
      mg/kg), and S-(1) (>= 30 mg/kg) dose-dependently lowered rectal body temperature
      with maximal doses of each Kv7 channel opener inducing a marked drop (>4 degrees
      C) in rectal temperature. The Kv7 channel openers showed differential temporal
      pharmacodynamics, which likely reflects their different pharmacokinetic profiles.
      Pretreatment with the pan-Kv7 channel blocker XE-991 (1.0mg/kg, i.p.) completely
      reversed the hypothermic effect of the pan-Kv7 opener, retigabine (15 mg/kg),
      whereas ICA-27243-induced hypothermia (10mg/kg) could only be partially prevented
      by XE-991. Because ICA-27743 and S-(1) are Kv7.2/3 channel subunit-preferring
      compounds, this suggests that the Kv7.2/3 channel isoform is the predominant
      substrate for Kv7 channel opener-evoked hypothermia. These data indicate the
      physiological relevance of Kv7 channel function on body temperature regulation
      which may potentially reside from central inhibitory Kv7 channel activity.

PMID- 21087655
TI  - Automatic cortical responses to sound movement: a magnetoencephalography study.
AB  - The aim of the present study was to clarify what change detection process leads
      to the elicitation of the auditory change-sensitive N1ms using
      magnetoencephalography (MEG). We brought our attention to whether these N1ms
      would be elicited if physical changes to the stimulus are eliminated. For this
      purpose, sound movement (SM), which entails a very subtle change only to the
      manner of stimuli presentation, was used in the present study. SM presentation
      was achieved by inserting an interaural time difference to one ear. The results
      indicate that both SM and the onset of the control stimulus (ON) elicited MEG
      responses at the superior temporal gyrus (STG) of both hemispheres. ON-N1m peak
      latencies were significantly shorter than those of SM-N1m as well. Interestingly,
      the pre-event (ON or SM) length (PreEL) was a significant factor determining the
      amplitude of the STG activity. Due to these findings, we hypothesize that both ON
      and SM activate similar groups of neurons or even an identical group of neurons.
      In addition, since correlations between PreEL and ON/SM-N1m amplitude exist, it
      is suggestible that N1m is not merely a nonspecific automatic response to
      physical change, but rather a much more sophisticated change-sensitive response
      employing a memory mechanism.

PMID- 21087657
TI  - Technical aspects of spinal cord injections for cell transplantation. Clinical
      and translational considerations.
AB  - Spinal cord injections may be used to transplant cellular suspensions for the
      experimental treatment of spinal cord injury. These injections cause some
      additional injury due to needle penetration, spinal cord motion during injection,
      creation of intraparenchymal pressure gradients and hydrodynamic dissection,
      instillation of a deforming cell mass and possible cord ischemia. It is important
      to understand these variables to maximize the safety of injections and avoid
      injury to spared structures. Surprisingly little knowledge exists regarding these
      variables. Further complicating spinal cord injections is the fact that
      intraparenchymal events are not evident during injections. As cell injections for
      spinal cord injury enter extensive clinical testing it is important to both
      optimize the procedures, and reduce the probability of technical failures. In
      this review current knowledge and key areas for knowledge advance are identified.
      These include a need for a more thorough understanding of how the spinal cord is
      affected by needle entry and dwell, needle-cord relative motion, instillation of
      highly concentrated cellular volumes, compliance of intact and damaged spinal
      cord tissue, radial tensile stresses and hydrodynamic forces created by
      injection, and the rates of pressure gradient dissipation in damaged and intact
      tissue. We propose that if the variables associated with injury can be
      identified, injection injury may be reduced and we illustrate the use of
      ultrasound to monitor injection in a spinal cord model. We also suggest that
      injectate backout or extrusion be reinterpreted as a clear indicator of excessive
      intraparenchymal pressure. The strengths and weaknesses of alternatives to direct
      intraparenchymal injection are also discussed.

PMID- 21087656
TI  - Haptic touch reduces sway by increasing axial tone.
AB  - It is unclear how haptic touch with a stable surface reduces postural sway. We
      hypothesized that haptic input enhances postural stability due to alterations in
      axial postural tone. We measured the influence of heavy and light touch (LT) of
      the hands on a stable bar on axial postural tone and postural sway during stance
      in 14 healthy adults. A unique "Twister" device measured hip torque by fixing the
      upper body in space while oscillating the surface in yaw +/-10 at 1 deg/s.
      Subjects were tested while: (1) standing quietly with their arms at their sides,
      (2) lightly touching a rigid bar in front of them and (3) firmly gripping the
      bar. Horizontal and vertical sway was not restricted by the device's yaw
      fixation, therefore, the subjects remained in a state of active postural control
      during the three touch conditions. Haptic touch significantly increased hip
      postural tone by 44% during light touch, from 2.5+/-0.9 to 3.6+/-1.0 Nm
      (P=0.005), and by 40% during firm grip to 3.5+/-0.8 Nm (P=0.005). Increases in
      hip postural tone were associated with a reduction in postural sway (r=-0.55,
      P=0.001). This is the first study showing that axial postural tone can be
      modified by remote somatosensory input and provides a potential explanation for
      how light touch improves postural stability. Changes in subjects' perception from
      trunk to surface rotation when changing from no touch (NT) to haptic touch,
      suggests that the CNS changes from using a global, to a local, trunk reference
      frame for control of posture during touch. The increase of hip postural tone
      during touching and gripping can be explained as a suppression of hip muscle
      shortening reactions that normally assist axial rotation.

PMID- 21087658
TI  - Leopard frog priorities in choosing between prey at different locations.
AB  - Frogs are able to respond to a prey stimulus throughout their 360 degrees  ground
      level visual field as well as in the superior visual field. We compared the
      likelihood of frogs choosing between a more nasally located, ground-level prey
      versus a more temporally located ground-level prey, when the prey at the nasal
      location is further away from the frog. Two crickets were presented
      simultaneously at 9 pairs of angles that included both crickets in the binocular
      visual field, both crickets in the monocular visual field, or one cricket in the
      binocular field and one in the monocular field. Frogs chose the more nasally
      located prey at least 71% of the time when the more temporal prey was in the
      monocular field; and 64% of the time when both prey were in the binocular field.
      Frogs tended to choose the more nasally located prey, even though it takes the
      frog longer to reach the prey. In addition, when given a choice between a prey
      located at ground level versus a prey located in the superior field, frogs tend
      to choose the prey at ground-level. These results suggest that there is a neural
      mechanism that biases frogs' responses to prey stimuli.

PMID- 21087659
TI  - Formaldehyde interferes with airway epithelium integrity and functions in a dose-
      and time-dependent manner.
AB  - Formaldehyde (HCHO) is a common indoor air pollutant. To assess its potential
      role and mechanism of action in asthma, we exposed the bronchial epithelial cell
      lines Calu-3 and 16HBE to HCHO (70-7000 MUM) according to two exposure schedules
      (30 min and 24 h), before measuring cell viability, necrosis and apoptosis,
      reactive oxygen species production, cytokine release, as well as trans-epithelial
      electrical resistance (TEER) of cell monolayers. Whereas exposure to HCHO for 30
      min had a limited effect on cell viability, exposure for 24h to 1400-7000 MUM
      HCHO induced a pronounced dose-dependent cell death. The important decrease in
      cell viability observed after 24h exposure to the highest concentrations of HCHO
      (1400-7000 MUM) was accompanied by important LDH release and ROS production,
      whereas a 4h exposure to lower HCHO concentrations (350 MUM) induced cell
      apoptosis. Also, exposure to HCHO for 30 min dose-dependently inhibited basal and
      lipopolysaccharide-induced interleukin-6 (IL-6) and IL-8 production by bronchial
      epithelial cells. As well, HCHO triggered a dose- and time-dependent decrease in
      TEER of Calu-3 cell monolayers. The present work demonstrates that HCHO
      interferes with airway epithelium integrity and functions, and may thus modulate
      the onset and the severity of asthma. However, importantly, conditions of
      exposure to HCHO, e.g. level and duration, are determinant in the nature of the
      effects triggered by the pollutant.

PMID- 21087660
TI  - Tumor selectivity of stealth multi-functionalized superparamagnetic iron oxide
      nanoparticles.
AB  - Superparamagnetic iron oxide nanoparticles (SPIO-NPs) have traditionally been
      used as MRI contrast agent for disease imaging via passive targeting. However,
      there has been an increasing interest in the development of SPIO-NPs to cellular
      specific targeting for imaging and drug delivery currently. The objective of our
      study was to develop a novel active tumor-targeting SPIO-NPs system by surface
      modifying superparamagnetic iron oxide nanoparticles (SPIO-NPs) with o
      carboxymethyl chitosans (OCMCS) and folic acid (FA) to improve their
      biocompatibility and ability to target specific tumor cells as well as to evade
      reticuloendothelial system (RES). The results in vitro indicated the covalent
      surface-modification of SPIO-NPs with OCMCS significantly reduced not only the
      nano-cytotoxicity but also the capture of SPIO-NPs by macrophage cells. On the
      other hand, the folic acid modification promoted the uptake of nanoparticles by
      FR-positive tumor cell lines, but had little impact on other cells without folate
      receptor (FR). MRI image and tumor histological analysis demonstrated the FA
      OCMCS-SPIO-NPs had the ability to target tumor cells with FR in vivo. OCMCS and
      folic acid modification of SPIO-NPs could significantly improve both the SPIO-NPs
      biocompatibility and the FR target for MRI imaging, potential carrier for drug
      targeting and hyperthermia.

PMID- 21087661
TI  - Distribution of catecholaminergic and peptidergic cells in the gerbil medial
      amygdala, caudal preoptic area and caudal bed nuclei of the stria terminalis with
      a focus on areas activated at ejaculation.
AB  - The posterodorsal preoptic nucleus (PdPN), lateral part of the posterodorsal
      medial amygdala (MeApd) and medial part of the medial preoptic nucleus (MPNm) are
      activated at ejaculation in male gerbils as assessed by Fos expression. We sought
      to immunocytochemically visualize substance P (SP), cholecystokinin (CCK),
      oxytocin, vasopressin and tyrosine hydroxylase (TH), a catecholaminergic marker,
      in the mating-activated cells, but the need for colchicine precluded behavioral
      testing. Instead, we detailed distributions of cells containing these molecules
      in the medial amygdala, caudal preoptic area and caudal bed nuclei of the stria
      terminalis (BST) and quantified their densities in the PdPN, MPNm and lateral
      MeApd for comparison to densities previously assessed for mating-activated
      efferents from these sites. TH cells were as dense in the PdPN and lateral MeApd
      as activated efferents to the anteroventral periventricular nucleus. In the
      lateral MeApd, TH cells were grouped where cells activated at ejaculation are
      clustered and where CCK cells form a ball. Lateral MeApd CCK cells and PdPN SP
      cells were as dense as activated efferents to the principal BST. Oxytocinergic
      PdPN cells and SP cells in the MPNm were as dense as mating-activated efferents
      to the lateral MeApd. If some oxytocin cells in the PdPN project to the
      neurohypophysis, as in rats, they could be a source of the oxytocin secreted at
      ejaculation. Since gerbils are monogamous and biparental, it was also interesting
      that, unlike monogamous prairie voles, they had few TH cells in the MeApd or
      dorsal BST, resembling promiscuous rats, hamsters and meadow voles.

PMID- 21087662
TI  - The "thrifty" gene encoding Ahsg/Fetuin-A meets the insulin receptor: Insights
      into the mechanism of insulin resistance.
AB  - Ahsg (fetuin-A) is a 55-59kDa phosphorylated glycoprotein synthesized in the
      adult predominantly by hepatocytes, from which it enters the circulation. When
      dysregulated, this glycoprotein operates to influence the clinical sequelae of
      insulin resistance-type 2 diabetes and cardiovascular disease. The pathological
      sequelae likely arise from two separable molecular "faces" of Ahsg-one acting at
      the level of the insulin receptor and a second face influencing ectopic
      biomineralization in the intima. A detailed understanding of these two functional
      faces of Ahsg is not yet clear for lack of structural studies. Ahsg has a
      physiological role in the biomineralization of bone, which when dysregulated can
      lead to ectopic calcification of soft tissues in the vasculature. Ahsg has a
      second physiological function in regulating how insulin signals through its
      receptor, a transmembrane tyrosine kinase. Dysregulation of this "face" of Ahsg
      results in morbid sequelae such as impaired glucose disposal and fatty liver.
      Ahsg binds to tandem fibronectin type 3 (Fn3) domains present in the 194 amino
      acid residue extracellular portion of the beta-subunit of the insulin receptor,
      distant from the high-affinity pocket formed by two complementing alpha-subunits
      where insulin binds. Only two proteins are known to bind directly to the insulin
      receptor ectodomain - insulin and Ahsg - the former turns on the receptor's
      intrinsic tyrosine kinase (TK) activity, and the latter shuts it down. Recent X
      ray crystallographic studies of the ectodomain of the insulin receptor now
      sharpen our understanding of the receptor's extracellular alpha-subunit and
      linked beta-subunit. Ahsg genotype and its circulating level have been correlated
      with body morphometrics (obese versus lean and visceral adiposity) in
      epidemiological studies enrolling thousands of patients. Epidemiological studies
      from the clinic reveal high levels of circulating Ahsg in insulin resistance and
      diabetes. This review endeavors to explain how one protein can mediate diverse
      pathologies, but specifically addresses its metabolic "face" blunting insulin
      receptor activity, an action leading to insulin resistance.

PMID- 21087663
TI  - Assemblage of drug release modules: effect of module shape and position in the
      assembled systems on floating behavior and release rate.
AB  - The aim of this work was to study the clindamycin release kinetics from floating
      delivery systems consisting of two modules assembled in void configuration,
      according to the modified release technology platform known as Dome Matrix(r).
      Two modules differently shaped, i.e., female and male, formulated as swellable
      matrices and containing clindamycin, were assembled by friction interlocking.
      Then, by stacking additional female modules without drug on the assembled two
      module floating system, modulation of clindamycin release rate and kinetics was
      attained. The additional modules stacked on the assembled system acted as a
      transient barrier to clindamycin release from the void configuration. Inertness,
      dissolution/erosion or swelling behavior characterized their performance as
      matrices in simulated gastric fluid. In particular, we found that stacking
      additional barrier modules on the bases of void configuration, the drug release
      rate and kinetics of the assembled system were modified in dependence on the
      composition of module added. In particular, the quickly soluble module exerted an
      influence on the release rate in the late time of delivery. The swellable module
      produced a significant reduction in release rate of void assembly, but the
      release mechanism remained the same. Finally, the inert module led to a
      substantial linearization of the release profile with a minimal reduction in
      release rate.

PMID- 21087664
TI  - BRCA1/BARD1 complex interacts with steroidogenic factor 1--A potential mechanism
      for regulation of aromatase expression by BRCA1.
AB  - Germline mutations in BRCA1 predispose women to early onset of breast and ovarian
      cancers. Findings from previous studies support the notion that the tissue- and
      gender-specific tumor suppression function of BRCA1 is associated with its role
      in negative regulation of aromatase expression, the rate-limiting step in
      estrogen biosynthesis. The molecular mechanism of BRCA1 in regulating aromatase
      promoter activity remains to be elucidated. In this study, we demonstrate that,
      in an ovarian granulosa cell line KGN, steroidogenic factor 1 (SF-1) is required
      for aromatase PII promoter basal activity as well as the elevated aromatase
      expression mediated by BRCA1 knockdown. Furthermore, BRCA1 in KGN cells exists
      mainly as a heterodimer with BARD1. We provide evidence that the BRCA1/BARD1
      complex interacts with SF-1 both in vivo and in vitro. However, the intrinsic
      ubiquitin E3 ligase activity of BRCA1/BARD1 does not appear to contribute to
      ubiquitynation of SF-1. We propose that the interaction between SF-1 and
      BRCA1/BARD1 may recruit BRCA1/BARD1 complex to the aromatase PII promoter for
      BRCA1/BARD1-mediate transcriptional repression.

PMID- 21087665
TI  - Inhibitors of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3): overview and
      structural insights.
AB  - There is considerable interest in the development of an inhibitor of aldo-keto
      reductase (AKR) 1C3 (type 5 17beta-hydroxysteroid dehydrogenase and prostaglandin
      F synthase) as a potential therapeutic for both hormone-dependent and hormone
      independent cancers. AKR1C3 catalyzes the reduction of 4-androstene-3,17-dione to
      testosterone and estrone to 17beta-estradiol in target tissues, which will
      promote the proliferation of hormone dependent prostate and breast cancers,
      respectively. AKR1C3 also catalyzes the reduction of prostaglandin (PG) H(2) to
      PGF(2alpha) and PGD(2) to 9alpha,11beta-PGF(2), which will limit the formation of
      anti-proliferative prostaglandins, including 15-deoxy-Delta(12,14)-PGJ(2), and
      contribute to proliferative signaling. AKR1C3 is overexpressed in a wide variety
      of cancers, including breast and prostate cancer. An inhibitor of AKR1C3 should
      not inhibit the closely related isoforms AKR1C1 and AKR1C2, as they are involved
      in other key steroid hormone biotransformations in target tissues. Several
      structural leads have been explored as inhibitors of AKR1C3, including non
      steroidal anti-inflammatory drugs, steroid hormone analogues, flavonoids,
      cyclopentanes, and benzodiazepines. Inspection of the available crystal
      structures of AKR1C3 with multiple ligands bound, along with the crystal
      structures of the other AKR1C isoforms, provides a structural basis for the
      rational design of isoform specific inhibitors of AKR1C3. We find that there are
      subpockets involved in ligand binding that are considerably different in AKR1C3
      relative to the closely related AKR1C1 or AKR1C2 isoforms. These pockets can be
      used to further improve the binding affinity and selectivity of the currently
      available AKR1C3 inhibitors. Article from the special issue on Targeted
      Inhibitors.

PMID- 21087667
TI  - Applications of analytical ultracentrifugation to protein size-and-shape
      distribution and structure-and-function analyses.
AB  - The rebirth of modern analytical ultracentrifugation (AUC) began in 1990s. Since
      then many advanced AUC detectors have been developed that provide a vast range of
      versatile choices when characterizing the physical and chemical features of
      macromolecules. In addition, there have been remarkable advances in software that
      allow the analysis of AUC data using more sophisticated models, including
      quaternary structures, conformational changes, and biomolecular interactions.
      Here we report the application of AUC to protein size-and-shape distribution
      analysis and structure-and-function analysis in the presence of ligands or
      lipids. Using band-sedimentation velocity, quaternary structural changes and an
      enzyme's catalytic activity can be observed simultaneously. This provides direct
      insights into the correlation between quaternary structure and catalytic activity
      of the enzyme. On the other hand, also in this study, we have applied size-and
      shape distribution analysis to a lipid-binding protein in either an aqueous or
      lipid environment. The sedimentation velocity data for the protein with or
      without lipid were evaluated using the c(s,f(r)) two-dimensional distribution
      model, which provides a precise and quantitative means of analyzing the protein's
      conformational changes.

PMID- 21087668
TI  - Expression, purification, detergent screening and solution NMR backbone
      assignment of the human potassium channel accessory subunit MiRP1.
AB  - MiRP1 (MinK related protein 1) is a membrane protein in the KCNE family. It can
      associate with and modulate various voltage gated potassium channels. Mutations
      in human MiRP1 have been found to cause many congenital and acquired long QT
      syndromes, which are potentially life-threatening cardiac arrhythmias. Here,
      human MiRP1 was over-expressed in Escherichia coli, purified and eluted into
      different detergents. Two dimensional (1)H-(15)N correlated solution nuclear
      magnetic resonance (NMR) spectra of the human MiRP1 in four different detergent
      micelles indicated that high resolution solution NMR spectrum can be obtained for
      human MiRP1 in detergent lyso-myristoylphosphatidylglycerol (LMPG). Circular
      dichroism (CD) spectroscopy of human MiRP1 indicated a high content of alpha
      helical secondary structure in LMPG. Backbone assignments of most MiRP1 residues
      were achieved through a series of triple resonance NMR experiments. Secondary
      structure analysis based on backbone chemical shifts showed several stretches of
      alpha-helices along the primary sequence of MiRP1 in LMPG.

PMID- 21087666
TI  - NF-kappaB in the mechanism of brain edema in acute liver failure: studies in
      transgenic mice.
AB  - Astrocyte swelling and brain edema are major complications of the acute form of
      hepatic encephalopathy (acute liver failure, ALF). While elevated brain ammonia
      level is a well-known etiological factor in ALF, the mechanism by which ammonia
      brings about astrocyte swelling is not well understood. We recently found that
      astrocyte cultures exposed to ammonia activated nuclear factor-kappaB (NF
      kappaB), and that pharmacological inhibition of such activation led to a
      reduction in astrocyte swelling. Although these findings suggest the involvement
      of NF-kappaB in astrocyte swelling in vitro, it is not known whether NF-kappaB
      contributes to the development of brain edema in ALF in vivo. Furthermore,
      pharmacological agents used to inhibit NF-kappaB may have non-specific effects.
      Accordingly, we used transgenic (Tg) mice that have a functional inactivation of
      astrocytic NF-kappaB and examined whether these mice are resistant to ALF
      associated brain edema. ALF was induced in mice by treatment with the hepatotoxin
      thioacetamide (TAA). Wild type (WT) mice treated with TAA showed a significant
      increase in brain water content (1.65%) along with prominent astrocyte swelling
      and spongiosis of the neuropil, consistent with the presence of cytotoxic edema.
      These changes were not observed in Tg mice treated with TAA. Additionally, WT
      mice with ALF showed an increase in inducible nitric oxide synthase (iNOS)
      immunoreactivity in astrocytes from WT mice treated with TAA (iNOS is known to be
      activated by NF-kappaB and to contribute to cell swelling). By contrast, Tg mice
      treated with TAA did not exhibit brain edema, histological changes nor an
      increase in iNOS immunoreactivity. We also examined astrocytes cultures derived
      from Tg mice to determine whether these cells exhibit a lesser degree of swelling
      and cytopathological changes following exposure to ammonia. Astrocyte cultures
      derived from Tg mice showed no cell swelling nor morphological abnormalities when
      exposed to ammonia for 24h. By contrast, ammonia significantly increased cell
      swelling (31.7%) in cultured astrocytes from WT mice and displayed cytological
      abnormalities. Moreover, we observed a lesser increment in iNOS and NADPH oxidase
      activity (the latter is also known to be activated by NF-kappaB and to contribute
      to astrocyte swelling) in astrocyte cultures from Tg mice treated with ammonia,
      as compared to ammonia-treated WT mice astrocytes. These findings strongly
      suggest that activation of NF-kappaB is a critical factor in the development of
      astrocyte swelling/brain edema in ALF.

PMID- 21087669
TI  - Molecular cloning, characterization and expression analysis of macrophage
      migration inhibitory protein (MIF) in Chinese mitten crab, Eriocheir sinensis.
AB  - Macrophage migration inhibitory factor (MIF) as a multi-functional cytokine
      mediating both innate and adaptive immune responses, however, their function
      within the innate immune system of invertebrates remains largely unknown.
      Therefore, we investigated the immune functionality of MIF in Chinese mitten crab
      (Eriocheir sinensis), a commercially important and disease vulnerable aquaculture
      species. The full-length MIF cDNA (704 bp) was cloned via PCR based upon an
      initial expressed sequence tag (EST) isolated from a E. sinensis cDNA library.
      The MIF cDNA contained a 363 bp open reading frame (ORF) that encoded a putative
      120 amino acid (aa) protein. Comparisons with other reported invertebrate and
      vertebrate MIF sequences revealed conserved enzyme active sites. MIF mRNA
      expression in E. sinensis was (a) tissue-specific, with the highest expression
      observed in hepatotpancreas, and (b) responsive in hemocytes, hepatopancreas and
      gill to a Vibrio anguillarum challenge, with peak exposure observed 8 h, 12 h and
      12 h post-injection, respectively. Collectively, data demonstrate the successful
      isolation of MIF from the Chinese mitten crab, and its involvement in the innate
      immune system of an invertebrate.

PMID- 21087670
TI  - Molecular cloning, characterization and expression analysis of TLR9, MyD88 and
      TRAF6 genes in common carp (Cyprinus carpio).
AB  - Induction of innate immune pathways is critical for early host defense, but there
      is limited understanding of how teleost fishes recognize pathogen molecules and
      activate these pathways. In mammals, cells of the innate immune system detect
      pathogenic molecular structures using pattern recognition receptors (PRRs). TLR9
      functions as a PRR that recognizes CpG motifs in bacterial and viral DNA and
      requires adaptor molecules MyD88 and TRAF6 for signal transduction. Here we
      report full-length cDNA isolation, structural characterization and tissue mRNA
      expression analysis of the common carp (cc) TLR9, MyD88 and TRAF6 gene orthologs.
      The ccTLR9 open-reading frame (ORF) is predicted to encode a 1064-amino acid (aa)
      protein. We found that MyD88 and TRAF6 genes are duplicated in common carp. This
      is the first report of TRAF6 duplication in a vertebrate genome and stronger
      evidence in support of MyD88 duplication is provided. The ccMyD88a and b ORFs are
      predicted to encode 288-aa and 284-aa peptides, respectively. They share 91% aa
      sequence identity between paralogs. The ccTRAF6a and b ORFs are both predicted to
      encode 543-aa peptides sharing 95% aa sequence identity between paralogs. The
      ccTLR9 gene is contained in a single large exon. The ccMyD88a and ccMyD88b coding
      sequences span five exons. The TRAF6b gene spans six exons. PCR amplification to
      obtain the entire coding sequence of ccTRAF6a gene was not successful. The 2104
      bp fragment amplified covers the 3' end of the gene and it contains a partial
      sequence of one exon and three complete exons. The predicated protein domains of
      the ccTLR9, ccMyD88 and ccTRAF6 are conserved and resemble orthologs from other
      vertebrates. Real-time quantitative PCR assays of the ccTLR9, MyD88a and b, and
      TRAF6a and b gene transcripts in healthy common carp indicated that mRNA
      expression varied between tissues. Differential expression of duplicate copies
      were found for ccMyD88 and ccTRAF6 in white and red muscle tissues, suggesting
      that paralogs may have evolved and attained a new function. The genomic
      information we describe in this paper provides evidence of sequence and
      structural conservation of immune response genes in common carp.

PMID- 21087671
TI  - Men and women are different: diffusion tensor imaging reveals sexual dimorphism
      in the microstructure of the thalamus, corpus callosum and cingulum.
AB  - INTRODUCTION: Numerous magnetic resonance imaging (MRI) studies have addressed
      the question of morphological differences of the brain of men and women,
      reporting conflicting results regarding brain size and the ratio of gray and
      white matter. In the present study, we used diffusion tensor imaging (DTI) to
      delineate sex differences of brain white matter. METHODS: We investigated brain
      microstructure in 25 male and 25 female healthy subjects using a 3T MRI scanner.
      Whole-head DTI scans were analyzed without a-priori hypothesis using Tract-Based
      Spatial Statistics (TBSS) calculating maps of fractional anisotropy (FA), radial
      diffusivity (RD, a potential marker of glial alteration and changes in
      myelination) and axial diffusivity (AD, a potential marker of axonal changes).
      RESULTS: DTI revealed regional microstructural differences between the brains of
      male and female subjects. Those were prominent in the thalamus, corpus callosum
      and cingulum. Men showed significantly (p<0.0001) higher values of fractional
      anisotropy and lower radial diffusivity in these areas, suggesting that the
      observed differences are mainly due to differences in myelination. DISCUSSION: As
      a novel finding we showed widespread differences in thalamic microstructure that
      have not been described previously. Additionally, the present study confirmed
      earlier DTI studies focusing on sexual dimorphism in the corpus callosum and
      cingulum. All changes appear to be based on differences in myelination. The sex
      differences in thalamic microstructure call for further studies on the underlying
      cause and the behavioral correlates of this sexual dimorphism. Future DTI group
      studies may carefully control for gender to avoid confounding.

PMID- 21087672
TI  - Beneficial network effects of methylene blue in an amnestic model.
AB  - Posterior cingulate/retrosplenial cortex (PCC) hypometabolism is a common feature
      in amnestic mild cognitive impairment and Alzheimer's disease. In rats, PCC
      hypometabolism induced by mitochondrial dysfunction induces oxidative damage,
      neurodegeneration and memory deficits. USP methylene blue (MB) is a
      diaminophenothiazine drug with antioxidant and metabolic-enhancing properties. In
      rats, MB facilitates memory and prevents neurodegeneration induced by
      mitochondrial dysfunction. This study tested the memory-enhancing properties of
      systemic MB in rats that received an infusion of sodium azide, a cytochrome
      oxidase inhibitor, directly into the PCC. Lesion volumes were estimated with
      unbiased stereology. MB's network-level mechanism of action was analyzed using
      graph theory and structural equation modeling based on cytochrome oxidase
      histochemistry-derived metabolic mapping data. Sodium azide infusions induced PCC
      hypometabolism and impaired visuospatial memory in a holeboard food-search task.
      Isolated PCC cytochrome oxidase inhibition disrupted the cingulo-thalamo
      hippocampal effective connectivity, decreased the PCC functional networks and
      created functional redundancy within the thalamus. An intraperitoneal dose of 4
      mg/kg MB prevented the memory impairment, reduced the PCC metabolic lesion volume
      and partially restored the cingulo-thalamo-hippocampal network effects. The
      effects of MB were dependent upon the local sub-network necessary for memory
      retrieval. The data support that MB's metabolic-enhancing effects are contingent
      upon the neural context, and that MB is able to boost coherent and orchestrated
      adaptations in response to physical alterations to the network involved in
      visuospatial memory. These results implicate MB as a candidate intervention to
      improve memory. Because of its neuroprotective properties, MB may have disease
      modifying effects in amnestic conditions associated with hypometabolism.

PMID- 21087673
TI  - D2 receptor genotype and striatal dopamine signaling predict motor cortical
      activity and behavior in humans.
AB  - OBJECTIVE: Pre-synaptic D2 receptors regulate striatal dopamine release and DAT
      activity, key factors for modulation of motor pathways. A functional SNP of DRD2
      (rs1076560 G>T) is associated with alternative splicing such that the relative
      expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor
      isoforms is decreased in subjects with the T allele with a putative increase of
      striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine
      signaling predict motor cortical activity and behavior in humans, we have
      investigated the association of rs1076560 with BOLD fMRI activity during a motor
      task. To further evaluate the relationship of this circuitry with dopamine
      signaling, we also explored the correlation between genotype based differences in
      motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I]
      FP-CIT SPECT. METHODS: Fifty healthy subjects, genotyped for DRD2 rs1076560 were
      studied with BOLD-fMRI at 3T while performing a visually paced motor task with
      their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT.
      SPM5 random-effects models were used for statistical analyses. RESULTS: Subjects
      carrying the T allele had greater BOLD responses in left basal ganglia, thalamus,
      supplementary motor area, and primary motor cortex, whose activity was also
      negatively correlated with reaction time at the task. Moreover, left striatal DAT
      binding and activity of left supplementary motor area were negatively correlated.
      INTERPRETATION: The present results suggest that DRD2 genetic variation was
      associated with focusing of responses in the whole motor network, in which
      activity of predictable nodes was correlated with reaction time and with striatal
      pre-synaptic dopamine signaling. Our results in humans may help shed light on
      genetic risk for neurobiological mechanisms involved in the pathophysiology of
      disorders with dysregulation of striatal dopamine like Parkinson's disease.

PMID- 21087674
TI  - Adding trastuzumab to standard chemotherapy in HER2-positive esophagogastric
      adenocarcinoma: a further step toward personalized medicine.

PMID- 21087675
TI  - Diagnosis of early hepatocellular carcinoma: ideal goal, but not yet there.

PMID- 21087677
TI  - In vivo structural analysis of subchondral trabecular bone in osteoarthritis of
      the hip using multi-detector row CT.
AB  - OBJECTIVE: With developments in clinical computed tomography (CT), in vivo
      analysis of patients' bone microstructure has become increasingly possible. We
      analyzed the subchondral trabecular bone of hip osteoarthritis (OA) patients
      using multi-detector row CT (MDCT) to closely examine the structural changes that
      occur as OA progresses. DESIGN: 47 female hip joints were studied: 20 with OA
      secondary to hip dysplasia (11 advanced OA, nine early-moderate OA), seven with
      hip dysplasia without OA, and 20 normal. The images' maximal spatial resolution
      was 280 * 280 * 500 MUm. Regions of interest (ROIs) were the subchondral
      trabecular bones of the acetabulum and femoral head. Measurement parameters were
      bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number
      (Tb.N), trabecular separation (Tb.Sp), structure model index (SMI), trabecular
      bone pattern factor (TBPf), Euler's number, and degree of anisotropy (DA).
      Relationships between joint space volume and these parameters were analyzed.
      RESULTS: With decreasing joint space, Tb.Th and BV/TV increased, and Tb.Sp, Tb.N,
      SMI, TBPf, and DA decreased significantly. The microstructures were significantly
      different between the early to advanced OA groups and the normal and dysplasia
      groups; there was no significant difference between the normal and dysplasia
      groups. CONCLUSIONS: Changes of subchondral trabecular bone structure in OA could
      be evaluated using MDCT, despite imperfect spatial resolution and limited
      accuracy. Trabecular bone thickening and associated structural changes may be
      closely related to OA. Changes were observed in early to advanced OA, but not in
      dysplasia. This method may help to further elucidate OA pathogenesis, determine
      the therapeutic strategy, and evaluate therapy.

PMID- 21087676
TI  - PTHrP overexpression partially inhibits a mechanical strain-induced arthritic
      phenotype in chondrocytes.
AB  - OBJECTIVE: Cell-based tissue engineering strategies are currently in clinical use
      and continue to be developed at a rapid pace for the repair of cartilage defects.
      Regardless of the repair methodology, chondrocytes within newly regenerated
      cartilage remain susceptible to the abnormal inflammatory and mechanical
      environments that underlie osteoarthritic disease, likely compromising the
      implant's integration, function, and longevity. The present study investigates
      the use of parathyroid hormone-related peptide (PTHrP) overexpression for
      chondroprotection. DESIGN: Bovine articular chondrocytes were transfected with
      human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious
      cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 h. mRNA expression
      of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes
      were examined with real-time reverse transcription polymerase chain reaction.
      Nitric oxide (NO) and prostaglandin E2 (PGE2) production were measured using the
      Griess assay and enzyme immunoassay (EIA), respectively. RESULTS: CTS-induced an
      arthritic phenotype in articular chondrocytes as indicated by increased gene
      expression of collagenases and aggrecanases and increased production of NO and
      PGE2. Additionally, CTS increased collagen type X (Col10a1) mRNA expression,
      whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1
      gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE2
      production, and neither hPTHrP isoform had any significant effect on apoptotic
      genes. CONCLUSIONS: Our results suggest that chondrocytes overexpressing PTHrP
      resist mechanical strain-induced hypertrophic-like changes. Therapeutic PTHrP
      gene transfer may be considered for chondroprotection applications in newly
      regenerated cartilage.

PMID- 21087678
TI  - Generic immunosuppressants in hematopoietic cell transplantation.

PMID- 21087680
TI  - Galactomannan testing in bronchoalveolar lavage fluid facilitates the diagnosis
      of invasive pulmonary aspergillosis in patients with hematologic malignancies and
      stem cell transplant recipients.
AB  - Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients
      with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA
      improves survival but is difficult to make. We evaluated the effectiveness of
      bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these
      populations by retrospectively reviewing records of 67 consecutive patients, in
      whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL
      sample linked to the IPA episode was analyzed. Eighty samples were associated
      with proven, 12 with probable, and 32 with possible invasive fungal infections
      (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had
      proven, 11 probable, and 32 possible IPA. Using BAL GM >= 0.5 (cutoff for serum
      GM) and >= 0.85 (optimal cutoff identified by receiver-operating characteristic
      curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and
      67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At
      these cutoffs, positive and negative predictive values were 73% (11/15) and 83%
      (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive
      than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%,
      2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was >= 0.85 and >= 0.5
      in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received
      a mold-active agent for <= 3 days. BAL GM added sensitivity to serum GM and other
      means of diagnosing IPA, and was not impacted by short courses of mold-active
      agents.

PMID- 21087679
TI  - Unrelated donor transplantation for acute myelogenous leukemia in first
      remission.
AB  - We retrospectively analyzed the outcomes of all acute myelogenous leukemia (AML)
      patients in first remission (n = 44; median age = 48 years; high-risk
      cytogenetics = 59%) who received unrelated donor hematopoietic cell
      transplantation (HCT) with myeloablative conditioning regimen of i.v. busulfan,
      fludarabine, and antithymocyte globulin (ATG) between January 2002 and November
      2009 at our institution. Donor-recipient pairs were matched by high-resolution
      HLA-A, -B, -C, -DRB1, and -DQB1 typing (10/10 matches, n = 41; 9/10 matches, n =
      3). With a median follow-up of 34 months, actuarial 3-year event-free survival
      (EFS) and overall survival (OS) is 70% and 78%, respectively. The 3-year EFS and
      OS in patients with and without poor risk cytogenetics is similar (63% versus
      82%, P = 0.43 and 78% versus 82%, P = .89, respectively). The 3-year EFS and OS
      is also similar in patients above age 55 year versus patients age 55 year or
      younger (80% versus 67%, P = .47 and 80% versus 78%, P = .81, respectively). The
      100-day and 3-year cumulative incidence of transplant-related mortality is 5% and
      15%, respectively. Six patients have relapsed, and 3 of them are alive and in
      remission after salvage therapy, with a median follow-up of 23 months. These
      results indicate that the majority of AML patients eligible for this treatment
      can achieve long-term disease control.

PMID- 21087682
TI  - Inappropriate implantable cardioverter-defibrillator therapy due to
      electromagnetic interference in patient with a HeartWare HVAD left ventricular
      assist device.

PMID- 21087681
TI  - Involvement of host calpain in the invasion of Cryptosporidium parvum.
AB  - Cryptosporidium parvum induces the formation of an actin-dense plaque which is
      essential for the successful invasion of epithelial cells. Host molecules that
      are involved in the regulation of this cytoskeleton reorganization are unknown.
      Here we identified that calcium-dependent thiol protease calpain is critical for
      regulating parasite-induced actin polymerization. C. parvum invasion induced
      activation of calpain. Inhibition of calpain activity by overexpression of the
      endogenous inhibitor calpastatin diminished the formation of the actin-dense
      plaque and decreased the initial invasion of parasites. Our data indicates a key
      role of calpain activity of host cell in C. parvum infection via regulating
      cytoskeleton reorganization.

PMID- 21087683
TI  - Re: Meta-analysis of the use of glyceryl trinitrate ointment after
      haemorrhoidectomy as an analgesic and in promoting wound healing.

PMID- 21087684
TI  - Brain abscess: an overview.
AB  - Intracranial abscess is a formidable entity. Despite the advent of newer
      antibiotics and surgical strategies, the overall outcome and quality of life
      issues in brain abscess patients still remain a continuous challenge for the
      neurosurgical community. It is a direct interplay between the virulence of the
      offending microorganism and the immune response of the host. An analysis of our
      experience in the 289 cases of surgically treated pyogenic brain abscess is
      presented along with an overview of intra-cranial abscess of varied etiology and
      in different locations. The etiology, pathogenesis, radiological advances and
      treatment modalities of brain abscess are discussed in light of current
      literature.

PMID- 21087685
TI  - The effect of preoperative renal dysfunction with or without dialysis on early
      postoperative outcome following cardiac surgery.
AB  - OBJECTIVES: Although previous studies have shown increased mortality in renal
      dysfunction patients undergoing cardiac surgery, there is lack of data on the
      pattern of postoperative complications that occur in such patients and their
      distribution among dialysis and non-dialysis dependent renal dysfunction.
      METHODS: This is a retrospective review of prospectively collected data over 8
      year period of cardiac surgery patients. Our cohort consisted of 3598 consecutive
      patients divided into: normal kidneys (n = 3276, 91%), renal dysfunction (n =
      277, 8%) and dialysis (n = 45, 1%). Postoperative complications and mortality
      were analysed. Multivariate analysis was conducted to adjust for the potential
      confounders in the association between renal dysfunction and postoperative
      complications. RESULTS: Univariate analysis showed increased risk of the
      following complications among renal dysfunction and dialysis patients: low
      cardiac output, arrhythmias, reoperation, prolonged ventilation, readmission to
      intensive care, blood transfusion and prolonged hospital stay. Mortality rate was
      highest in dialysis patients compared to renal dysfunction and normal kidney
      patients (11% vs. 7% vs. 3%, respectively p-value <0.001). Multivariate analysis
      showed that renal dysfunction with or without dialysis is an independent
      predictor of postoperative low cardiac output, blood transfusion, prolonged
      ventilation, and mortality. The odd ratios were higher for dialysis than non
      dialysis dependent patients. This effect persisted after adjusting for potential
      confounders such as age and gender. CONCLUSION: The presence of renal dysfunction
      preoperatively increases the rate of postoperative complications and mortality
      following cardiac surgery. Prior knowledge of these complications can help in
      developing preventative strategies to reduce the associated risk.

PMID- 21087686
TI  - Age-related changes in bone density, geometry and biomechanical properties of the
      proximal femur: CT-based 3D hip structure analysis in normal postmenopausal
      women.
AB  - The geometry as well as bone mineral density (BMD) of the proximal femur
      contributes to fracture risk. How and the extent to which they change due to
      natural aging is not fully understood. We assessed BMD and geometry in the
      femoral neck and shaft separately, in 59 normal Japanese postmenopausal women
      aged 54-84 years, using clinical computed tomography (CT) and commercially
      available software, at baseline and 2-year follow-up. This system detected
      significant reductions over the 2-year interval in total BMD (%change/year = 
      0.900 +/- 0.257, p < 0.0005), cortical cross-sectional area (CSA) (-0.800 +/-
      0.423%/year, p < 0.05) and cortical thickness (-1.120 +/- 0.453%/year, p < 0.01)
      in the femoral neck. In the femoral shaft, cortical BMD decreased significantly (
      0.642 +/- 0.188%/year, p < 0.005). Regarding biomechanical parameters in the
      femoral neck, the cross-sectional moment of inertia (CSMI) and section modulus
      (SM) decreased (-1.38 +/- 3.65%/year, p < 0.01 and -1.37 +/- 2.96%/year, p <
      0.005) and the buckling ratio (BR) increased significantly (1.48 +/- 4.81%/year,
      p < 0.05), whereas no changes were found in the femoral shaft. The distinct
      patterns of age-related changes in the geometry and biomechanical properties in
      the femoral neck and shaft suggest that improved geometric measures are possible
      with the current non-invasive method using clinical CT.

PMID- 21087687
TI  - The use of immunization registry-based data in vaccine effectiveness studies.
AB  - Vaccine effectiveness (VE) studies provide a measure of population-based vaccine
      performance by combining immunization history data with rates of disease
      incidence. This review assessed the feasibility of using electronic immunization
      registry data sources in VE studies. Electronic databases were searched through
      January 31, 2010. Out of 17 studies, only one paper assessed data accuracy (71%),
      and three papers assessed population coverage of the registry (estimates ranged
      from 25% to 90%). This review shows that registry-based data sources can be used
      to conduct VE studies in a variety of settings and populations. However, we found
      little information regarding the quality of this data source in VE studies and
      future evaluations should investigate their reliability, accuracy, and potential
      bias.

PMID- 21087689
TI  - An alpha-GalCer analogue with branched acyl chain enhances protective immune
      responses in a nasal influenza vaccine.
AB  - alpha-Galactosylceramide (alpha-GalCer) is a safe and effective adjuvant for
      nasal vaccines and induces protective immune responses against tumors and viral
      infections. In our previous study, the fatty acyl chains of alpha-GalCer were
      modified based on the CD1d/glycolipid structure to generate alpha-GalCer
      analogues with branched acyl chains. In this study, two alpha-GalCer analogues,
      KBC-007 and KBC-009, that have different branched chain lengths were prepared and
      evaluated for their efficacy as nasal influenza vaccine adjuvants. These
      analogues displayed improved solubility over alpha-GalCer and potently stimulated
      NKT cells in both murine and in vitro human systems. Examination of serum
      cytokines in vivo revealed that these analogues elicited different cytokine
      release profiles compared to alpha-GalCer. KBC-009 induced both Th1/Th2
      cytokines, whereas KBC-007 induced a more Th2-polarized cytokine response with
      diminished IFN-gamma production. We found that a single immunization of
      inactivated influenza virus A/PR/8/34 (PR8) combined with alpha-GalCer analogues
      enhanced PR8-specific humoral and cellular immune responses in both systemic and
      mucosal compartments. Notably, KBC-009 exhibited potent adjuvant effects,
      inducing significantly higher systemic IgG and mucosal IgA antibody titers and
      enhancing cytotoxic T lymphocyte generation when compared to immunization with
      inactivated PR8 alone. In contrast, addition of KBC-007 to inactivated PR8 only
      marginally increased PR8-specific immune responses. The protective effect of KBC
      009 against challenge infection was comparable to the effect produced by alpha
      GalCer. These results suggest that an alpha-GalCer analogue with a branched acyl
      chain could be used as an effective mucosal adjuvant for the induction of
      protective immune responses against influenza virus infection.

PMID- 21087698
TI  - The benefits of having a National Institute of Child Health and Human
      Development.

PMID- 21087690
TI  - Evaluation of three recombinant multi-antigenic vaccines composed of surface and
      secretory antigens of Toxoplasma gondii in murine models of experimental
      toxoplasmosis.
AB  - The great clinical and economical impact of Toxoplasma gondii infections makes
      the development of an effective vaccine for controlling toxoplasmosis an
      extremely important aim. In the presented study, we evaluate the protective and
      immunogenic properties of three recombinant subunit vaccines composed of
      rROP2+rGRA4+rSAG1, rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 proteins of T. gondii
      in an experimental toxoplasmosis model in the C3H/HeJ and C57BL/6 mouse strains.
      All three recombinant vaccines induced partial protection as measured by the
      reduction of brain cyst burden following challenge with five tissue cysts of the
      low virulence DX T. gondii strain. The level of protection was dependent on the
      antigen composition of the vaccine and the genetic background of the laboratory
      animals. The strongest protection against chronic toxoplasmosis was induced in
      both C3H/HeJ and C57BL/6 mice by the mixture of rhoptry proteins rROP2 and rROP4
      combined with tachyzoite major protein rSAG1. The average parasite burden in
      these groups of mice was reduced by 71% and 90%, respectively, compared to non
      vaccinated mice. The observed protective effect was related to the vaccine
      induced cellular and humoral immune responses, as measured by the antigen-induced
      release of the Th1 cytokines IFN-gamma and IL-2, the antigen-stimulated
      proliferation of spleen cells of vaccinated animals in comparison to control
      animals and the development of systemic antigen-specific IgG1 and IgG2a (C3H/HeJ)
      or IgG2c (C57BL/6) antibodies. Our studies show that recombinant rROP2, rROP4,
      rGRA4 and rSAG1 antigens may be promising candidates for a subunit vaccine
      against toxoplasmosis. Additionally, we demonstrate that the ideal composition of
      vaccine antigens can be equally effective in mice with different genetic
      backgrounds and variable levels of innate resistance to toxoplasmosis, resulting
      in strong protection against T. gondii invasion.

PMID- 21087704
TI  - Paradoxical embolism via an atrial septal defect: in flagrante delicto.

PMID- 21087705
TI  - The evolving role of inflammatory biomarkers in risk assessment after stent
      implantation.
AB  - The main adverse reactions to coronary stents are in-stent restenosis (ISR) and
      stent thrombosis. Along with procedural factors, individual susceptibility to
      these events plays an important role. In particular, inflammatory status, as
      assessed by C-reactive protein levels, predicts the risk of ISR after bare-metal
      stent implantation, although it does not predict the risk of stent thrombosis.
      Conversely, C-reactive protein levels fail to predict the risk of ISR after drug
      eluting stent (DES) implantation, although they appear to predict the risk of
      stent thrombosis. Of note, DES have abated ISR rates occurring in the classical 1
      year window, but new concern is emerging regarding late restenosis and
      thrombosis. The pathogenesis of these late events seems to be related to delayed
      healing and allergic reactions to polymers, a process in which eosinophils seem
      to play an important role by enhancing restenosis and thrombosis. The
      identification of high-risk individuals based on biomarker assessment may be
      important for the management of patients receiving stent implantation. In this
      report, we review the evolving role of inflammatory biomarkers in predicting the
      risk of ISR and stent thrombosis.

PMID- 21087706
TI  - Randomized, controlled trial of individualized heparin and protamine management
      in infants undergoing cardiac surgery with cardiopulmonary bypass.
AB  - OBJECTIVES: We sought to determine whether infants (younger than 1 year old) had
      similar clinical benefits with individualized anticoagulation management as older
      children and adult undergoing cardiopulmonary bypass (CPB). BACKGROUND:
      Individualized heparin and protamine management in older children and adults
      undergoing CPB has been associated with improved clinical outcomes. METHODS:
      Ninety infants younger than 1 year of age undergoing CPB were enrolled in a
      randomized, controlled trial comparing weight-based anticoagulation management
      using activated clotting time (ACT) to individualized management with Hemostasis
      Management System Plus. Manufacturer's guidelines were followed for the first 33
      patients. A modified protocol was used for the last 57 patients with adjustments
      for coagulation system immaturity and hemodilution on CPB. RESULTS: The
      hemostasis management system (HMS) device consistently underestimated plasma anti
      Xa levels, leading to an overestimated required heparin dose. After a blinded
      interim analysis revealed poor outcomes in the experimental HMS group using
      manufacturer guidelines, the safety committee suspended the study pending
      protocol modifications. The use of the HMS device following the modified protocol
      resulted in more stable anti-Xa levels during CPB with improved post-operative
      outcomes including reduced need for transfusions (71 ml/kg vs. 80 ml/kg; p =
      0.003), ventilation time (33 h vs. 49 h; p = 0.04), intensive care (88 h vs. 99
      h; p = 0.003), and hospital length of stay (192 h vs. 216 h; p < 0.001), compared
      with the weight-based protocol. CONCLUSIONS: This study supports the use of the
      HMS device, with a modified protocol for infants younger than 1 year of age, for
      anticoagulation management during CPB. Clinical guidelines for the use of the HMS
      device should be modified for infants younger than 1 year of age.

PMID- 21087707
TI  - Urban particulate matter air pollution is associated with subclinical
      atherosclerosis: results from the HNR (Heinz Nixdorf Recall) study.
AB  - OBJECTIVES: The aim of this study was to investigate the association of long-term
      residential exposure to fine particles with carotid intima-media thickness
      (CIMT). BACKGROUND: Experimental and epidemiological evidence suggest that long
      term exposure to air pollution might have a causal role in atherogenesis, but
      epidemiological findings are still inconsistent. We investigate whether urban
      particulate matter (PM) air pollution is associated with CIMT, a marker of
      subclinical atherosclerosis. METHODS: We used baseline data (2000 to 2003) from
      the HNR (Heinz Nixdorf Recall) study, a population-based cohort of 4,814
      participants, 45 to 75 years of age. We assessed residential long-term exposure
      to PM with a chemistry transport model and measured distance to high traffic.
      Multiple linear regression was used to estimate associations of air pollutants
      and traffic with CIMT, adjusting for each other, city of residence, age, sex,
      diabetes, and lifestyle variables. RESULTS: Median CIMT of the 3,380 analyzed
      participants was 0.66 mm (interquartile range 0.16 mm). An interdecile range
      increase in PM(2.5) (4.2 MUg/m(3)), PM(10) (6.7 MUg/m(3)), and distance to high
      traffic (1,939 m) was associated with a 4.3% (95% confidence interval [CI]: 1.9%
      to 6.7%), 1.7% (95% CI: -0.7% to 4.1%), and 1.2% (95% CI: -0.2% to 2.6%) increase
      in CIMT, respectively. CONCLUSIONS: Our study shows a clear association of long
      term exposure to PM(2.5) with atherosclerosis. This finding strengthens the
      hypothesized role of PM(2.5) as a risk factor for atherogenesis.

PMID- 21087708
TI  - Does air pollution accelerate progression of atherosclerosis?

PMID- 21087709
TI  - Longitudinal and circumferential strain rate, left ventricular remodeling, and
      prognosis after myocardial infarction.
AB  - OBJECTIVES: We sought to investigate the clinical prognostic value of
      longitudinal and circumferential strain (S) and strain rate (SR) in patients
      after high-risk myocardial infarction (MI). BACKGROUND: Left ventricular (LV)
      contractile performance after MI is an important predictor of long-term outcome.
      Tissue deformation imaging might more closely reflect myocardial contractility
      than traditional measures of systolic functions. METHODS: The VALIANT (Valsartan
      in Acute Myocardial Infarction Trial) Echo study enrolled 603 patients with LV
      dysfunction, heart failure, or both 5 days after MI. We measured global peak
      longitudinal S and systolic SR (SRs) from apical 4- and 2-chamber views and
      global circumferential S and SRs from parasternal short-axis view with speckle
      tracking software (Velocity Vector Imaging, Siemens, Inc., Mountain View,
      California). We related global S and SRs to LV remodeling at 20-month follow-up
      and to clinical outcomes. RESULTS: Both longitudinal (mean: -5.1 +/- 1.6 100/ms)
      and circumferential SRs (mean: -8.0 +/- 2.8 100/ms) were predictive of death or
      hospital stay for heart failure (hazard ratio: 2.4, 95% confidence interval [CI]:
      2.0 to 3.1, p < 0.001; hazard ratio: 1.3, 95% CI: 1.2 to 1.4, p < 0.001,
      respectively) after adjustment for clinical covariates by Cox proportional
      hazards, and longitudinal SRs further improved in predicting 18-month survivor on
      a model based on clinical and standard echocardiographic measures (increase in
      area under the receiver-operator characteristic curve: 0.13, p = 0.009). With
      multivariable logistic regression, circumferential SRs, but not longitudinal SRs,
      was strongly predictive of remodeling (odds ratio: 1.3, 95% CI: 1.1 to 1.4, p <
      0.001). CONCLUSIONS: Both longitudinal and circumferential SRs were independent
      predictors of outcomes after MI, whereas only circumferential SRs was predictive
      of remodeling, suggesting that preserved circumferential function might serve to
      restrain ventricular enlargement after MI.

PMID- 21087710
TI  - Risk stratification after myocardial infarction: toward novel quantitative
      assessment of left ventricular mechanics?

PMID- 21087711
TI  - Cardiac resynchronization therapy in asymptomatic or mildly symptomatic heart
      failure patients in relation to etiology: results from the REVERSE
      (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction)
      study.
AB  - OBJECTIVES: The purpose of this study was to determine the effects of cardiac
      resynchronization therapy (CRT) with respect to heart failure etiology among
      patients in the REVERSE (REsynchronization reVErses Remodeling in Systolic Left
      vEntricular Dysfunction) study. BACKGROUND: CRT improves outcomes in New York
      Heart Association functional class III/IV heart failure with wide QRS with a more
      pronounced effect on left ventricular (LV) reverse remodeling in nonischemic
      patients. METHODS: A total of 277 patients with nonischemic heart disease (IHD)
      and 333 with IHD etiology in New York Heart Association functional class I or II
      with QRS >=120 ms and left ventricular ejection fraction <=40% received a CRT (+/
      implantable cardioverter-defibrillator) and were randomized to CRT-ON or CRT-OFF
      for 12 months. The primary end point was the percentage of patients worsened by
      the HF clinical composite response, and multiple prespecified secondary end
      points were evaluated regarding etiology using univariable and multivariable
      analysis. RESULTS: At baseline, IHD patients were significantly older and had
      more comorbidities and less dyssynchrony than non-IHD patients. In non-IHD
      patients, 10% worsened in CRT-ON compared with 19% in CRT-OFF (p = 0.01). In IHD
      patients, 20% worsened in the CRT-ON compared with 24% in the CRT-OFF group (p =
      0.10). Non-IHD patients assigned to CRT-ON improved more in left ventricular end
      systolic volume index than IHD patients. Randomization to CRT, left bundle branch
      block, and wider QRS duration independently predicted response to both end
      points, whereas non-IHD etiology was an independent predictor only for left
      ventricular end-systolic volume index. CONCLUSIONS: This substudy of REVERSE
      shows that CRT reverses left ventricular remodeling with a more extensive effect
      on nonischemic patients. Etiology was, however, not an independent predictor of
      clinical response. (REsynchronization reVErses Remodeling in Systolic Left
      vEntricular Dysfunction [REVERSE]; NCT00271154).

PMID- 21087712
TI  - Real-time dynamic carbon dioxide administration: a novel treatment strategy for
      stabilization of periodic breathing with potential application to central sleep
      apnea.
AB  - OBJECTIVES: This study targeted carbon dioxide (CO(2)) oscillations seen in
      oscillatory ventilation with dynamic pre-emptive CO(2) administration.
      BACKGROUND: Oscillations in end-tidal CO(2) (et-CO(2)) drive the ventilatory
      oscillations of periodic breathing (PB) and central sleep apnea in heart failure
      (HF). METHODS: Seven healthy volunteers simulated PB, while undergoing dynamic
      CO(2) administration delivered by an automated algorithm at different
      concentrations and phases within the PB cycle. The algorithm was then tested in 7
      patients with HF and PB. RESULTS: In voluntary PB, the greatest reduction (74%, p
      < 0.0001) in et-CO(2) oscillations was achieved when dynamic CO(2) was delivered
      at hyperventilation; when delivered at the opposite phase, the amplitude of et
      CO(2) oscillations increased (35%, p = 0.001). In HF patients, oscillations in et
      CO(2) were reduced by 43% and ventilatory oscillations by 68% (both p < 0.05).
      During dynamic CO(2) administration, mean et-CO(2) and ventilation levels
      remained unchanged. Static CO(2) (2%, constant flow) administration also
      attenuated spontaneous PB in HF patients (p = 0.02) but increased mean et-CO(2)
      (p = 0.03) and ventilation (by 45%, p = 0.03). CONCLUSIONS: Dynamic CO(2)
      administration, delivered at an appropriate time during PB, can almost eliminate
      oscillations in et-CO(2) and ventilation. This dynamic approach might be
      developed to treat central sleep apnea, as well as minimizing undesirable
      increases in et-CO(2) and ventilation.

PMID- 21087713
TI  - Respiratory instability in patients with chronic heart failure.

PMID- 21087714
TI  - Endothelial function and vascular response to mental stress are impaired in
      patients with apical ballooning syndrome.
AB  - OBJECTIVES: The aim of the current study was to test the hypothesis that vascular
      and endothelial functional responses to acute mental stress are abnormal in
      patients with apical ballooning syndrome (ABS). BACKGROUND: Apical ballooning
      syndrome is a transient cardiomyopathy that occurs predominantly in post
      menopausal women and may be triggered by acute mental stress. The mechanism for
      ABS is unknown. METHODS: Reactive hyperemia as a parameter of endothelial
      function and vascular responses to acute mental stress were measured using
      peripheral arterial tonometry (PAT) at baseline and following 3 acute mental
      stress tests in female patients with ABS (n = 12, at least 6 months after being
      hospitalized or diagnosed with ABS), post-menopausal female controls (n = 12),
      and female patients with myocardial infarction (MI) (n = 4). Plasma catecholamine
      levels were measured at baseline and following the 3 mental stress tests.
      RESULTS: Reactive hyperemia PAT scores following mental stress were significantly
      lower in patients with ABS compared with post-menopausal controls (p < 0.05). The
      PAT scores during mental stress were significantly lower in patients with ABS
      compared with patients with MI and post-menopausal controls (p < 0.05). There
      were no differences in PAT scores during acute mental stress in patients with MI
      versus post-menopausal controls. Furthermore, catecholamine levels were
      significantly increased in patients with ABS, compared with post-menopausal
      controls, following acute mental stress testing (p < 0.05). CONCLUSIONS: There is
      increased vascular reactivity and decreased endothelial function in response to
      acute mental stress in patients with a prior episode of ABS. The findings
      implicate vasomotor dysfunction as a potential mechanism involved in the
      pathogenesis of this unique cardiomyopathy.

PMID- 21087715
TI  - A new monocyte chemotactic protein-1/chemokine CC motif ligand-2 competitor
      limiting neointima formation and myocardial ischemia/reperfusion injury in mice.
AB  - OBJECTIVES: A nonagonist monocyte chemotactic protein-1 (MCP-1/CCL2) mutant
      (PA508) with increased affinity for glycosaminoglycans and thus competing with
      CCL2 was evaluated as a candidate for preventing neointima formation or
      myocardial ischemia/reperfusion injury. BACKGROUND: Myocardial infarction (MI)
      remains a major cause of death worldwide despite improved interventional and
      therapeutic options. Therefore, the discovery of drugs that limit restenosis
      after intervention and post-MI damage remains an important challenge. METHODS:
      The function of PA508 was assessed in functional assays in vitro and in mouse
      models of wire-induced neointima formation and experimental MI. RESULTS: PA508
      was functionally inactive in CC chemokine receptor 2 (CCR2) binding and calcium
      influx but inhibited monocyte chemotaxis or transendothelial migration toward
      CCL2, suggesting that it interferes with CCL2 presentation. In wild-type but not
      CCR2-deficient mice, PA508 reduced inflammatory leukocyte recruitment without
      affecting differential leukocyte counts, CCL2 levels, organ function, or
      morphology, indicating that it specifically attenuates the CCL2-CCR2 axis.
      Compared with vehicle, daily intraperitoneal injection of PA508 significantly (p
      < 0.05, n = 5) reduced neointimal plaque area and mononuclear cell infiltration
      in carotid arteries of hyperlipidemic apolipoprotein E-deficient mice while
      increasing smooth muscle cell content. In C57Bl/6J mice that underwent myocardial
      ischemia/reperfusion, treatment with PA508 significantly reduced infarction size,
      monocyte infiltration, and collagen and myofibroblast content in the infarction
      area and preserved heart function compared with vehicle (p < 0.05, n = 4 to 8).
      CONCLUSIONS: Here we demonstrate that administration of a rationally designed
      CCL2 competitor reduced inflammatory monocyte recruitment, limited neointimal
      hyperplasia, and attenuated myocardial ischemia/reperfusion injury in mice and
      could therefore be envisioned as a combined therapeutic approach for restenosis
      and MI.

PMID- 21087716
TI  - A picture is worth a thousand words: giant aneurysm of the interatrial septum.

PMID- 21087717
TI  - Drug therapy for hypercholesterolemia: time to end the double standard.

PMID- 21087719
TI  - Misinterpretation of prostate cancer data.

PMID- 21087722
TI  - [Scientific activities and publications of the College of the pulmonologists of
      the general French hospital centers (CPHG)].

PMID- 21087721
TI  - ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for
      cardiac computed tomography. A report of the American College of Cardiology
      Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular
      Computed Tomography, the American College of Radiology, the American Heart
      Association, the American Society of Echocardiography, the American Society of
      Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the
      Society for Cardiovascular Angiography and Interventions, and the Society for
      Cardiovascular Magnetic Resonance.
AB  - The American College of Cardiology Foundation (ACCF), along with key specialty
      and subspecialty societies, conducted an appropriate use review of common
      clinical scenarios where cardiac computed tomography (CCT) is frequently
      considered. The present document is an update to the original CCT/cardiac
      magnetic resonance (CMR) appropriateness criteria published in 2006, written to
      reflect changes in test utilization, to incorporate new clinical data, and to
      clarify CCT use where omissions or lack of clarity existed in the original
      criteria (1). The indications for this review were drawn from common applications
      or anticipated uses, as well as from current clinical practice guidelines. Ninety
      three clinical scenarios were developed by a writing group and scored by a
      separate technical panel on a scale of 1 to 9 to designate appropriate use,
      inappropriate use, or uncertain use. In general, use of CCT angiography for
      diagnosis and risk assessment in patients with low or intermediate risk or
      pretest probability for coronary artery disease (CAD) was viewed favorably,
      whereas testing in high-risk patients, routine repeat testing, and general
      screening in certain clinical scenarios were viewed less favorably. Use of
      noncontrast computed tomography (CT) for calcium scoring was rated as appropriate
      within intermediate- and selected low-risk patients. Appropriate applications of
      CCT are also within the category of cardiac structural and functional evaluation.
      It is anticipated that these results will have an impact on physician decision
      making, performance, and reimbursement policy, and that they will help guide
      future research.

PMID- 21087723
TI  - [First intention management of obstructive sleep apnea syndrome (OSAS) by custom
      made mandibular advancement device: the medium-term results. Prospective study by
      the General Hospital Pneumologists College (CPHG)].
AB  - OBJECTIVES: To demonstrate the efficacy and tolerance of present generation
      mandibular advancement devices in the first intention treatment for obstructive
      sleep apnea syndrome (OSAS), even when severe, after one year. METHODS: Between
      June 2006 and December 2007, 152 patients (male: 77%; age: 50.9+/-10.9 years;
      BMI: 26.3+/-3.6 kg/m(2); AHI: 25.5+/-13.9), without previous treatment,
      requesting management other than continuous positive pressure and dentally apt
      for a mandibular advancement device, were pre-included in a prospective one-year
      multicenter study (13 general hospitals). RESULTS: One hundred and twenty-nine
      patients were assessed at least once after fitting. The efficacy was noted as of
      day 90: the overall AHI fell from 24.8 to 10.8 (from 40.6 to 17.7 in the 40
      patients with AHI>30) and the Epworth index decreased from 11.2 to 6.9 (12.8 to
      8.1 for AHI>30). The AHI reduction was independent of gender, age, BMI and
      baseline AHI. The efficacy was maintained throughout the study period. Only eight
      patients withdrew for adverse events and seven for reasons of therapeutic
      failure. CONCLUSION: Mandibular advancement devices proved effective in first
      intention, including severe OSAS. No predictive individual efficacy factors
      emerged.

PMID- 21087724
TI  - [Pleuropulmonary manifestations of necrotising vasculitis].
AB  - The pleuropulmonary manifestations of necrotising vasculitis are frequent and
      polymorphic. If the existence of extrapulmonary signs and the presence of
      neutrophil polynuclear anticytoplasmic antibodies are helpful for the diagnosis
      of a bout of vasculitis, the existence of pleuropulmonary symptoms can also make
      for discussion of infections or iatrogenic effects induced by immunosuppressive
      treatments.

PMID- 21087725
TI  - [Treatment specifics for spontaneous pneumothorax in flight personnel].
AB  - Spontaneous pneumothorax is one cause of aeronautical unfitness in flight
      personnel, because of the risk of recurrence in flight, making it an issue of
      flight safety. Specific treatment is required for fighter pilots, pilots flying
      single-pilot and pilots in professional training: surgical synthesis via video
      thoracoscopy is obligatory from the first episode. Considering the exposure to an
      accumulation of aeronautical factors that are likely to encourage pneumothorax
      recurrence in flight, it is apical pleurectomy together with abrasion of the
      remaining pleura and resection of bullae/blebs that is required for fighter
      pilots to allow them to recover aeronautical fitness unrestrictedly. For all
      other categories of flight personnel, treatment is no different from that of the
      common patient. Knowledge of these treatment specifics is essential, to avoid
      unnecessary systematic surgical indication for all flight personnel, or
      jeopardise professional fitness in some of them due to inappropriate treatment.

PMID- 21087726
TI  - [Mediastinal pathology: pathological treatment of frozen section].
AB  - Tumoral pathology of the mediastinum is extremely varied, with different
      prognoses and treatments. The pathological examination is essential, both
      etiologically and prognostically. Mediastinoscopy is generally used to check for
      lymph node metastases, bronchopulmonary carcinoma, but also, to a lesser degree,
      for the exploration of isolated mediastinal adenopathy. Finally, this technique
      enables a diagnostic approach to mediastinal tumours. The frozen section has its
      place, at the first indication, making it possible to prescribe neoadjuvant
      chemotherapy, and in the other situations to make sure that the quantity of
      material removed is sufficient or even to carry out complementary techniques.

PMID- 21087728
TI  - [Pulmonary vein leiomyosarcoma extending into the left atrium].
AB  - In this paper, the authors report the case of a 28-year-old man with pulmonary
      vein leiomyosarcoma presenting subacute respiratory distress. Thoracic computed
      tomography and transoesophagal ultrasonographic examination of the heart
      suggested the diagnosis of a heart tumour revealed by the obstruction of the
      mitral valve and pulmonary oedema. Emergency cardiac surgery revealed the mass to
      be a leiomyosarcoma, probably extending from the right inferior pulmonary vein
      and extending into the left atrium. The clinical evolution was complicated
      because of a sudden local relapse. The patient underwent a second cardiac
      intervention involving lower right lobectomy followed by adjuvant chemotherapy
      with an ifosfamide-adriamycin combination. This treatment failed to control the
      disease and a third cardiac intervention was necessary with second-line
      gemcitabine-paclitaxel adjuvant chemotherapy. Further recurrences were observed
      with metastases first in the scalp and then in the spine and adrenal glands
      leading to the death of the patient 2 years after the diagnosis.

PMID- 21087727
TI  - [Impact of positron emission tomography on clinical management of potentially
      resectable non-small-cell lung cancer: a French prospective multicenter study].
AB  - BACKGROUND: Whole-body (18)F-deoxyglucose positron emission tomography (FDG-PET)
      has the potential to improve the management of non-small-cell lung cancer
      (NSCLC). We prospectively evaluated the impact of combining FDG-PET with
      conventional staging methods, including computed tomography (CT), on the staging
      and management of patients with potentially resectable NSCLC. METHODS: Ninety
      four consecutive patients with newly diagnosed/suspected NSCLC were enrolled.
      Each patient was first staged by using conventional methods, and then by FDG-PET.
      FDG-PET results were forwarded in a sealed envelope and divulged at the weekly
      staff meeting on staging and treatment, only after "Decision 1", based on
      conventional staging, had been reached by consensus; reevaluation taking FDG-PET
      into account yielded "Decision 2". The validity of these latter decisions was
      analyzed retrospectively. RESULTS: Eighty-nine patients were eligible. Relative
      to standard imaging, FDG-PET led to clinical staging changes in 26 (29.2%)
      patients. The stage was lowered in eight cases (9%) and raised in 18 cases
      (20.2%). "Decision 2" differed from "Decision 1" in 19 patients, modifying the
      surgical procedure in four cases, indicating other investigations to confirm FDG
      PET evidence of metastases in 12 cases, or modifying the medical treatment in
      three cases. These modifications were retrospectively justified in 9/19 cases,
      and consisted of 2/4 modifications of the surgical procedure (one hilar and one
      adrenal metastasis not confirmed histologically), 4/12 further investigations
      (axillary and liver biopsies, mediastinoscopy, occult colon cancer) and three
      indications for palliative treatment, in patients who all died within 3 months
      after FDG-PET. CONCLUSIONS: Based on FDG-PET, management was modified in 19/89
      (21.3%) patients, but these changes were justified in only 9/89 patients (10.1%).
      FDG-PET can detect asymptomatic local and distant metastases and improves the
      preoperative assessment of NSCLC, thereby avoiding unnecessary surgery. However,
      histological verification is required because of the risk of false-positive
      results.

PMID- 21087729
TI  - [Pulmonary fibrosis and arterial hypertension revealing a chronic pulmonary
      schistosomiasis. An unusual diagnosis in Europe].
AB  - We report on the case of a Senegalese woman who was hospitalised in Paris for
      dyspnea on exertion, revealing pulmonary fibrosis and arterial hypertension. With
      no evident etiology of this fibrosis, a surgical pulmonary biopsy was performed
      and revealed granulomatosis due to schistosomiasis. Diagnosis of chronic
      pulmonary schistosomiasis was obtained. The manifestations of the chronic
      pulmonary schistosomiasis include miliary and pulmonary arterial hypertension.
      Certain forms can lead to fibrosis as our case study illustrates and pose
      diagnostic problems outside parasitic endemic areas. Beside cases of acute
      schistosomiasis observed in tourists, the possibility of chronic forms of the
      disease in migrant originating from endemic areas should be recognised in
      industrialised countries.

PMID- 21087730
TI  - [Lymph node supraclavicular metastasis of thymic carcinoma: an inaugural and
      unusual feature of a rare disease].
AB  - Among the epithelial tumours of the thymus, thymic carcinomas are rare, involving
      more aggressive locoregional behaviour and a poor prognosis. More than one-third
      of cases present lymph node metastasis during an evaluation of the extension of a
      primitive mediastinal tumour of thymic origin. The authors report an unusual case
      in a 46-year-old woman presenting a metastatic form. The diagnosis of epidermoid
      thymic carcinoma was based on the histopathological examination of a right
      supraclavicular lymph node, associated with an anterior radiological mediastinal
      tumoral syndrome, raising the delicate problem of its diagnosis and treatment.

PMID- 21087731
TI  - Diarrhoea risk factors in enterally tube fed critically ill patients: a
      retrospective audit.
AB  - OBJECTIVE: Diarrhoea in the enterally tube fed (ETF) intensive care unit (ICU)
      patient is a multi-factorial problem. Diarrhoeal aetiologies in this patient
      cohort remain debatable; however, the consequences of diarrhoea have been well
      established and include electrolyte imbalance, dehydration, bacterial
      translocation, peri anal wound contamination and sleep deprivation. This study
      examined the incidence of diarrhoea and explored factors contributing to the
      development of diarrhoea in the ETF, critically ill, adult patient. METHOD: After
      institutional ethical review and approval, a single centre medical chart audit
      was undertaken to examine the incidence of diarrhoea in ETF, critically ill
      patients. Retrospective, non-probability sequential sampling was used of all
      emergency admission adult ICU patients who met the inclusion/exclusion criteria.
      RESULTS: Fifty patients were audited. Faecal frequency, consistency and quantity
      were considered important criteria in defining ETF diarrhoea. The incidence of
      diarrhoea was 78%. Total patient diarrhoea days (r=0.422; p=0.02) and total
      diarrhoea frequency (r=0.313; p=0.027) increased when the patient was ETF for
      longer periods of time. Increased severity of illness, peripheral oxygen
      saturation (Sp02), glucose control, albumin and white cell count were found to be
      statistically significant factors for the development of diarrhoea. CONCLUSION:
      Diarrhoea in ETF critically ill patients is multi-factorial. The early
      identification of diarrhoea risk factors and the development of a diarrhoea risk
      management algorithm is recommended.

PMID- 21087732
TI  - Biomarker promise for Parkinson's disease.

PMID- 21087733
TI  - Gene therapy for Parkinson's disease: do we have the cure?

PMID- 21087735
TI  - Measuring muscle strength in clinical trials.

PMID- 21087736
TI  - Accurate prevalence and uptake of testing for Huntington's disease.

PMID- 21087737
TI  - Vaccination and Dravet syndrome.

PMID- 21087739
TI  - Stroke scans and radiation risk.

PMID- 21087740
TI  - Alim-Louis Benabid: stimulation and serendipity.

PMID- 21087743
TI  - Neurological complications of systemic cancer.
AB  - Neurological complications of systemic cancer-those arising outside the nervous
      system-can be distressing, disabling, and sometimes fatal. Diagnosis is often
      difficult because different neurological disorders may present with similar signs
      and symptoms. Furthermore, comorbid neurological illnesses, common in elderly
      patients with cancer, can complicate diagnosis. Early diagnosis and aggressive
      treatment can improve neurological symptoms and can substantially enhance a
      patient's quality of life. We approach the problem of neurological complications
      of systemic cancer as would a neurologist: first by identifying the anatomical
      area or areas that are affected (ie, brain, spinal cord, peripheral nerve), then
      by evaluating the diagnostic approach, considering the symptoms and signs and
      including appropriate laboratory tests, and finally, by recommending treatment.
      We focus on disorders that are difficult to diagnose, need neurological
      consultation, and for which effective treatments exist.

PMID- 21087742
TI  - Pharmacological management of symptoms in multiple sclerosis: current approaches
      and future directions.
AB  - Management of symptoms in multiple sclerosis (MS) has received little attention
      compared with disease-modifying treatments. However, the effect of these symptoms
      on quality of life can be profound. Clinical trials of pharmacological drugs to
      treat symptoms of MS have often been underpowered and have used inappropriate
      measures of outcome. Many currently used symptomatic drugs were introduced
      decades ago, when study quality was considerably below current standards.
      Therefore, the evidence base on which to make clinical decisions is less than
      adequate. Interest in pharmacological treatment of symptoms in MS has increased
      in recent years, and several large randomised controlled trials have been
      reported. Pharmacological strategies are a core component of the treatment of
      these symptoms, but it is imperative to remember that a multidisciplinary
      rehabilitation approach is needed for effective management.

PMID- 21087744
TI  - The global experience with percutaneous aortic valve replacement.
AB  - Transcatheter aortic valve replacement is now a viable option in the treatment of
      high-risk severe symptomatic aortic stenosis. This review describes the current
      data with this technology and also the potential for the future role of the
      technology, including potential ways to yet further improve the short- and longer
      term results.

PMID- 21087745
TI  - Outcomes after transcatheter aortic valve implantation with both Edwards-SAPIEN
      and CoreValve devices in a single center: the Milan experience.
AB  - OBJECTIVES: Our aim was to assess clinical outcome after transcatheter aortic
      valve implantation (TAVI) performed with the 2 commercially available valves with
      3 delivery approaches selected in a stepwise fashion. BACKGROUND: Limited data
      exist on the results of a comprehensive TAVI program using different valves with
      transfemoral, transapical, and transaxillary approaches for treatment of severe
      aortic stenosis. METHODS: We report 30-day and 6-month outcomes of high-risk
      patients consecutively treated in a single center with either the Medtronic
      CoreValve (MCV) (Medtronic, Minneapolis, Minnesota) or Edwards-SAPIEN valve (ESV)
      (Edwards Lifesciences, Irvine, California) delivered via the transfemoral or
      transaxillary approaches and ESV via the transapical approach. RESULTS: A total
      of 137 patients underwent TAVI: 107 via transfemoral (46 MCV and 61 ESV), 15 via
      transaxillary (12 MCV and 3 ESV), and 15 via transapical approach. After the
      transfemoral approach, the procedural success rate was 93.5%, and major vascular
      complication rate was 20.6%. No intra-procedural deaths occurred. The procedural
      success rates of transapical and transaxillary approaches were 86.6% and 93.3%,
      respectively. The 30-day mortality rate was 0.9% in transfemoral group and 13.3%
      in transapical, and no deaths occurred after transaxillary access. Cumulative
      death rate at 6 months was 12.2% in transfemoral, 26.6% in transapical, and 18.2%
      in transaxillary groups. At multivariable analysis, logistic European System for
      Cardiac Operative Risk Evaluation, body surface area, and history of
      cerebrovascular disease were significantly associated with an increased risk of
      major adverse cardiac and cerebrovascular events. CONCLUSIONS: Routine TAVI using
      both MCV and ESV with a selection of approaches is feasible and allows treatment
      of a wide range of patients with good overall procedural success rates and 30-day
      and 6-month outcomes.

PMID- 21087746
TI  - Transcatheter aortic valve implantation in patients with bicuspid aortic valve
      stenosis.
AB  - OBJECTIVES: We evaluated transcatheter aortic valve implantation (TAVI) in high
      risk patients with bicuspid aortic valve (BAV) stenosis. BACKGROUND: TAVI shows
      promise in the treatment of severe stenosis of triscupid aortic valves,
      especially in high-risk patients. However, BAV stenosis has been considered a
      contraindication to TAVI. METHODS: Eleven patients (age 52 to 90 years) with
      symptomatic severe BAV stenosis underwent TAVI at 3 Canadian tertiary hospitals
      between May 2006 and April 2010. All patients were considered high risk for
      surgical aortic valve replacement. Edwards-SAPIEN transcatheter heart valves
      (Edwards Lifesciences, Inc., Irvine, California) were used. Transfemoral or
      transapical access was selected, depending on the adequacy of femoral access.
      RESULTS: Access was transfemoral in 7 patients and transapical in 4 patients.
      There were no intraprocedural complications. Significant symptomatic and
      hemodynamic improvement was observed in 10 of 11 patients. Baseline aortic valve
      area of 0.65 +/- 0.17 cm(2) and mean transaortic pressure gradient of 41 +/- 22.4
      mm Hg were improved to 1.45 +/- 0.3 cm(2) and 13.4 +/- 5.7 mm Hg, respectively.
      Two patients had moderate perivalvular leaks. At the 30-day follow-up there were
      2 deaths due to multisystem failure in 2 transapical patients. In 1 patient an
      undersized, suboptimally positioned, unstable valve required late conversion to
      open surgery. CONCLUSIONS: TAVI in selected high-risk patients with severe BAV
      stenosis can be successfully performed with acceptable clinical outcomes but will
      require further evaluation.

PMID- 21087747
TI  - Embolic cerebral insults after transapical aortic valve implantation detected by
      magnetic resonance imaging.
AB  - OBJECTIVES: This study assessed the rate of periprocedural embolic ischemic brain
      injury during transapical aortic valve replacement in 25 consecutive patients.
      BACKGROUND: Transcatheter aortic valve implantation is rapidly being established
      as a new therapeutic approach for aortic valve stenosis. Although initial
      clinical results are promising, it is unknown whether mobilization and
      embolization of calcified particles may lead to cerebral ischemia. METHODS:
      Twenty-five consecutive patients (10 men, 15 women, mean age: 81 +/- 5 years,
      mean log EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 32 +/
      10%) scheduled for transapical aortic valve implantation were included. All
      patients received a baseline cerebral magnetic resonance imaging scan. The scan
      was repeated approximately 6 days after valve implantation. The magnetic
      resonance imaging studies included axial diffusion-weighted, T(2)-weighted, fluid
      attenuated inversion recovery-weighted, and T(2) gradient echo sequences.
      Standardized assessment of the neurologic status was performed before aortic
      valve replacement and post-operatively. RESULTS: Transapical aortic valve
      implantation was successfully performed in all patients. In 17 patients (68%),
      new cerebral lesions could be detected, whereas 8 patients showed no new cerebral
      insults. The pattern of distribution and morphology were typical of embolic
      origin. Despite the high incidence of morphologically detectable lesions, only 5
      patients showed clinical neurologic alterations. Out of these patients, only 1
      suffered from a permanent stroke. CONCLUSIONS: New embolic ischemic cerebral
      insults are detected in 68% of patients after transapical valve implantation.
      Clinical symptoms are rare and usually transitory. Larger trials will need to
      establish the clinical significance of asymptomatic ischemic lesions as well as
      the rate of ischemic events in patients undergoing transfemoral valve
      replacement.

PMID- 21087748
TI  - An embolic deflection device for aortic valve interventions.
AB  - OBJECTIVES: We describe initial human experience with a novel cerebral embolic
      protection device. BACKGROUND: Cerebral emboli are the major cause of procedural
      stroke during percutaneous aortic valve interventions. METHODS: With right radial
      artery access, the embolic protection device is advanced into the aortic arch.
      Once deployed a porous membrane shields the brachiocephalic trunk and the left
      carotid artery deflecting emboli away from the cerebral circulation. Embolic
      material is not contained or removed by the device. The device was used in 4
      patients (mean age 90 years) with severe aortic stenosis undergoing aortic
      balloon valvuloplasty (n = 1) or transcatheter aortic valve implantation (n = 3).
      RESULTS: Correct placement of the embolic protection device was achieved without
      difficulty in all patients. Continuous brachiocephalic and aortic pressure
      monitoring documented equal pressures without evidence of obstruction to cerebral
      perfusion. Additional procedural time due to the use of the device was 13 min
      (interquartile range: 12 to 16 min). There were no procedural complications. Pre
      discharge cerebral magnetic resonance imaging found no new defects in any of 3
      patients undergoing transcatheter aortic valve implantation and a new 5-mm acute
      cortical infarct in 1 asymptomatic patient after balloon valvuloplasty alone. No
      patient developed new neurological symptoms or clinical findings of stroke.
      CONCLUSIONS: Embolic protection during transcatheter aortic valve intervention
      seems feasible and might have the potential to reduce the risk of cerebral
      embolism and stroke.

PMID- 21087749
TI  - Front stroke, back stroke: the "emerging" interest of stroke in transcatheter
      aortic valve implantation.

PMID- 21087751
TI  - Complications and outcome of balloon aortic valvuloplasty in high-risk or
      inoperable patients.
AB  - OBJECTIVES: This study aimed to determine the success, complications, and
      survival of patients after balloon aortic valvuloplasty (BAV). BACKGROUND: The
      introduction of transcatheter aortic valve implantation (TAVI) BAV has led to a
      revival in the treatment of patients with severe aortic stenosis. METHODS: A
      cohort of 262 patients with severe aortic stenosis underwent 301 BAV procedures.
      Of these, 39 (14.8%) patients had >=2 BAV procedures. Clinical, hemodynamic, and
      follow-up mortality data were collected. RESULTS: The cohort mean age was 81.7 +/
      9.8 years, and the mean Society of Thoracic Surgeons and logistic EuroSCORE
      (European System for Cardiac Operative Risk Evaluation) was 13.3 +/- 6.7 and 45.6
      +/- 21.6, respectively. BAV was performed as a bridge to TAVI or to surgical
      aortic valve replacement in 28 patients (10.6%) and for symptom relief in 234
      (89.4%). The mean aortic valve area (AVA) increased from 0.58 +/- 0.3 cm(2) to
      0.96 +/- 0.3 cm(2) (p < 0.001). Of these, 111 (45.0%) had final AVA >1 cm(2), and
      in 195 patients (79%), AVA increased by >40%. De novo BAV resulted in a higher
      mean increase in AVA 0.41 +/- 0.24 cm(2) versus 0.28 +/- 0.24 cm(2) in redo BAV
      (p = 0.003). Serious adverse events occurred in 47 patients (15.6%),
      intraprocedural death in 5 (1.6%), stroke in 6 (1.99%), coronary occlusion in 2
      (0.66%), severe aortic regurgitation in 4 (1.3%), resuscitation/cardioversion in
      5 (1.6%), tamponade in 1 (0.33%), and permanent pacemaker in 3 (0.99%). A
      vascular complication occurred in 21 patients (6.9%); 34 (11.3%) had a post
      procedure rise in creatinine >50%; and 3 (0.99%) required hemodialysis. During
      median follow-up of 181 days, the mortality rate was 50% (n = 131). The mortality
      rate in the group with final AVA >1 cm(2) was significantly lower than in the
      group with final AVA of <1 cm(2) (36.4% vs. 57.9%, p < 0.001). Final AVA was
      associated with lower mortality (hazard ratio: 0.46, p = 0.03). BAV as a bridge
      to TAVI or surgical aortic valve replacement had a better outcome compared with
      BAV alone: mortality rate 7 (25%) versus 124 (52.9%), respectively (p < 0.0001).
      CONCLUSIONS: Long-term survival is poor after BAV alone. BAV as a bridge to
      percutaneous or surgical aortic valve replacement is feasible, safe, and
      associated with better outcome than BAV alone.

PMID- 21087750
TI  - Renal function as predictor of mortality in patients after percutaneous
      transcatheter aortic valve implantation.
AB  - OBJECTIVES: The aim of this study was to determine the influence of baseline
      renal function and periprocedural acute kidney injury (AKI) on prognosis after
      transcatheter aortic valve implantation (TAVI). BACKGROUND: Evidence is growing
      that renal function is a major predictor of mortality in patients after TAVI.
      METHODS: TAVI was performed with the 18-F CoreValve prosthesis via transfemoral
      access. All-cause mortality was determined 30 days and 1 year after TAVI in 77
      patients with a mean Society of Thoracic Surgeons mortality score of 9.3 +/- 6.1%
      and a mean logistic European System for Cardiac Operative Risk Evaluation of 31.2
      +/- 17.6%. RESULTS: Overall procedural success rate was 98% with 1 periprocedural
      death. The 30-day mortality was 10%, and 1-year mortality was 26%. The mortality
      risk increased stepwise across quartiles of baseline serum creatinine. An AKI
      occurred in 20 of 77 patients: 12 patients (60%) with AKI died during follow-up.
      The incidence of AKI was related to peripheral arterial disease (65% vs. 39%; p =
      0.04), the occurrence of a systemic inflammatory response syndrome (60% vs. 21%,
      p = 0.002), and post-procedural peri-prosthetic regurgitation >=2+ (35% vs. 9%, p
      = 0.02). Impaired renal function at baseline reflected by serum creatinine >=1.58
      mg/dl (hazard ratio: 3.9, 95% confidence interval: 1.6 to 9.5; p = 0.002) and the
      occurrence of AKI (hazard ratio: 5.9, 95% confidence interval: 2.4 to 14.5, p <
      0.001) that was not related to the amount of contrast dye were strong predictors
      of 1-year mortality after TAVI. CONCLUSIONS: Impaired renal function at baseline
      and the occurrence of periprocedural AKI, independent whether renal function
      returns to baseline or not, are strong predictors of 30-day and 1-year mortality
      after TAVI.

PMID- 21087752
TI  - Multislice computed tomography for prediction of optimal angiographic deployment
      projections during transcatheter aortic valve implantation.
AB  - OBJECTIVES: This study assessed whether multislice computed tomography (MSCT)
      could predict optimal angiographic projections for visualizing the plane of the
      native valve and facilitate accurate positioning during transcatheter aortic
      valve implantation (TAVI). BACKGROUND: Accurate device positioning during TAVI
      depends on valve deployment in angiographic projections perpendicular to the
      native valve plane, but these may be difficult to determine. METHODS: Twenty
      patients underwent MSCT before TAVI. Using a novel technique, multiple
      angiographic projections accurately representing the native valve plane in
      multiple axes were determined. The accuracy of all predicted projections was
      determined post-procedure using angiography according to new criteria, based on
      valve perpendicularity and the degree of strut overlap (defined as excellent,
      satisfactory, or poor). The accuracy of valve deployment using MSCT was compared
      with the results of 20 consecutive patients undergoing TAVI without such MSCT
      angle prediction. RESULTS: Correct final deployment projections were more
      frequent in the MSCT-guided compared with non-MSCT-guided group: excellent or
      satisfactory projections (90% vs. 65%, p = 0.06). The MSCT angle prediction was
      accurate but dependent on optimal images (optimal images: 93% of predicted angles
      were excellent or satisfactory, suboptimal images: 73% of predicted angles were
      poor). A "line of perpendicularity" could be generated with optimal projections
      across the right-to-left anterior oblique plane by adding the correct cranial or
      caudal angulation. CONCLUSIONS: Pre-procedural MSCT can predict optimal
      angiographic deployment projections for implantation of transcatheter valves. An
      ideal deployment angle curve or "line of perpendicularity" can be generated.
      Understanding and applying these principles improves the accuracy of valve
      deployment and may improve outcomes.

PMID- 21087753
TI  - Use of anticoagulant agents and risk of bleeding among patients admitted with
      myocardial infarction: a report from the NCDR ACTION Registry--GWTG (National
      Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes
      Network Registry--Get With the Guidelines).
AB  - OBJECTIVES: The aim of this study was to evaluate anticoagulant use patterns and
      bleeding risk in a contemporary population of patients with acute coronary
      syndrome. BACKGROUND: Current practice guidelines support the use of
      unfractionated heparin, low molecular weight heparin, bivalirudin, or
      fondaparinux in non-ST-segment elevation myocardial infarction (NSTEMI) and ST
      segment elevation myocardial infarction (STEMI). Little is known about how these
      agents are selected in clinical practice. METHODS: Between January 2007 and June
      2009, data were captured for 72,699 patients with NSTEMI and 48,943 patients with
      STEMI at 360 U.S. hospitals for the NCDR ACTION Registry-GWTG (National
      Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes
      Network Registry-Get With the Guidelines). Patients were categorized based on
      anticoagulant strategy selected during hospitalization and their CRUSADE (Can
      Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes
      With Early Implementation of ACC/AHA [American College of Cardiology/American
      Heart Association] Guidelines) bleeding risk category. RESULTS: At least 1
      anticoagulant was administered to 66,279 patients (91.2%) with NSTEMI and 46,149
      patients (94.3%) with STEMI. Among STEMI patients, unfractionated heparin was
      most commonly used (66%), followed by bivalirudin (14%) and low molecular weight
      heparin (8%). In NSTEMI patients, unfractionated heparin was also the most
      commonly used anticoagulant (42%), followed by low molecular weight heparin (27%)
      and then bivalirudin (13%). There were significant differences in anticoagulant
      use by age, risk factors, concomitant medications, and invasive care. There was a
      5-fold difference in the rate of bleeding between patients in the lowest and
      highest CRUSADE bleeding risk groups, which was consistently observed in most
      anticoagulant groups. CONCLUSIONS: There is a wide variability in the use of
      anticoagulant regimens with significant differences according to baseline
      characteristics and concomitant therapies. Major bleeding is common, though a
      great degree of the variability in the rate of bleeding is largely based on
      differences in baseline characteristics, comorbidities, and invasive treatment
      strategies, rather than specific anticoagulant regimens.

PMID- 21087754
TI  - Rear-view mirror observations on bleeding in acute coronary syndromes.

PMID- 21087755
TI  - The effect of shear stress on neointimal response following sirolimus- and
      paclitaxel-eluting stent implantation compared with bare-metal stents in humans.
AB  - OBJECTIVES: We aimed to explore the relationship of neointimal thickness (NT) to
      shear stress (SS) after implantation of sirolimus-eluting stents (SES) and
      paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS). We then
      tested the hypothesis that drug elution attenuates the SS effect. BACKGROUND:
      Neointimal thickness after BMS implantation has been associated with SS;
      pertinent data for drug-eluting stents (DES) are limited. METHODS: Three
      dimensional coronary artery and stent reconstruction was performed in 30 patients
      at 6-month follow-up after SES (n = 10), PES (n = 10), or BMS (n = 10)
      implantation. Baseline SS at the stent surface was calculated using computational
      fluid dynamics and NT at follow-up was computed in 3-dimensional space. RESULTS:
      Neointimal thickness was lower in DES versus BMS (0.03 +/- 0.07 mm vs. 0.16 +/-
      0.08 mm, p < 0.001) and maximum NT was reduced in SES versus PES (0.33 +/- 0.13
      mm vs. 0.46 +/- 0.13 mm, p = 0.025). In the total population, both SS (slope: 
      0.05 mm/Pa, p < 0.001) and DES (coefficient for DES vs. BMS: -0.17 mm, p = 0.003)
      were independent predictors of NT. Subgroup analysis demonstrated a significant
      negative relationship of NT to SS in PES (slope: -0.05 mm/Pa, p = 0.016) and BMS
      (slope: -0.05 mm/Pa, p = 0.001). Sirolimus elution significantly attenuated the
      effect of SS on NT (interaction coefficient for SES vs. BMS: 0.04 mm/Pa, p =
      0.023), whereas the SS effect remained unchanged in PES (interaction coefficient
      for PES vs. BMS: 0.01 mm/Pa, p = 0.71). CONCLUSIONS: Neointimal thickness is
      significantly correlated (inversely) to SS in PES as in BMS. Sirolimus elution
      abrogates the SS effect on the neointimal response following stent implantation,
      whereas the SS effect is unchanged in PES.

PMID- 21087756
TI  - A comparison of the conformability of everolimus-eluting bioresorbable vascular
      scaffolds to metal platform coronary stents.
AB  - OBJECTIVES: The aim of this study was to assess the differences in terms of
      curvature and angulation of the treated vessel after the deployment of either a
      metallic stent or a polymeric scaffold device. BACKGROUND: Conformability of
      metallic platform stents (MPS) is the major determinant of geometric changes in
      coronary arteries caused by the stent deployment. It is not known how
      bioresorbable polymeric devices perform in this setting. METHODS: This
      retrospective study compares 102 patients who received an MPS (Multi-link Vision
      or Xience V, Abbott Vascular, Santa Clara, California) in the SPIRIT FIRST and II
      trials with 89 patients treated with the Revision 1.1 everolimus-eluting
      bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California)
      from cohort B of the ABSORB (A bioabsorbable everolimus-eluting coronary stent
      system) trial. All patients were treated with a single 3 * 18 mm device.
      Curvature and angulation were measured with dedicated software by angiography.
      RESULTS: Both the MPS and BVS groups had significant changes in relative region
      curvature (MPS vs. BVS: 28.7% vs. 7.5%) and angulation (MPS vs. BVS: 25.4% vs.
      13.4%) after deployment. The unadjusted comparisons between the 2 groups showed
      for BVS a nonsignificant trend for less change in region curvature after
      deployment (MPS vs. BVS: 0.085 cm(-1) vs. 0.056 cm(-1), p = 0.06) and a
      significantly lower modification of angulation (MPS vs. BVS 6.4 degrees  vs. 4.3
      degrees , p = 0.03). By multivariate regression analysis, the independent
      predictors of changes in curvature and angulation were the pre-treatment region
      curvature, the pre-treatment region angulation, and the used device. CONCLUSIONS:
      Bioresorbable vascular scaffolds have better conformability than conventional
      MPS. The clinical significance of the observed differences will require further
      investigation.

PMID- 21087757
TI  - In vivo assessment of local intravascular hemodynamics and arterial morphology to
      investigate vascular outcomes: a growing field coming of age.

PMID- 21087758
TI  - Neovascular microchannels in sirolimus-eluting stent occlusion at late phase.

PMID- 21087759
TI  - Acute coronary syndrome with clear coronary artery: the case for concealed
      coronary hematoma.

PMID- 21087760
TI  - Trials, triumphs, and tribulations.

PMID- 21087764
TI  - Identification of multiple compartments present during the mastication of solid
      food.
AB  - The particle size distributions (PSDs) of two portion sizes (2g and 4g) of five
      foods (cake, cereal bar, muesli bar, cooked pasta and peanuts) after human
      mastication were determined. The PSD of the expectorated bolus and residual
      'debris' rinsed from the mouth were each determined by wet sieving. There were
      significant differences in the PSD between food types, between portion sizes in
      the debris fraction and between the bolus and debris fractions. The latter
      suggests the existence of a two compartment system where particles are comminuted
      in at least one compartment within the oral cavity.

PMID- 21087763
TI  - Genome-wide screen identifies rs646776 near sortilin as a regulator of
      progranulin levels in human plasma.
AB  - Recent studies suggest progranulin (GRN) is a neurotrophic factor. Loss-of
      function mutations in the progranulin gene (GRN) cause frontotemporal lobar
      degeneration (FTLD), a progressive neurodegenerative disease affecting ~10% of
      early-onset dementia patients. Using an enzyme-linked immunosorbent assay, we
      previously showed that GRN is detectable in human plasma and can be used to
      predict GRN mutation status. This study also showed a wide range in plasma GRN
      levels in non-GRN mutation carriers, including controls. We have now performed a
      genome-wide association study of 313,504 single-nucleotide polymorphisms (SNPs)
      in 533 control samples and identified on chromosome 1p13.3 two SNPs with genome
      wide significant association with plasma GRN levels (top SNP rs646776; p = 1.7 *
      10-30). The association of rs646776 with plasma GRN levels was replicated in two
      independent series of 508 controls (p = 1.9 * 10-19) and 197 FTLD patients (p =
      6.4 * 10-12). Overall, each copy of the minor C allele decreased GRN levels by
      ~15%. SNP rs646776 is located near sortilin (SORT1), and the minor C allele of
      rs646776 was previously associated with increased SORT1 mRNA levels. Supporting
      these findings, overexpression of SORT1 in cultured HeLa cells dramatically
      reduced GRN levels in the conditioned media, whereas knockdown of SORT1 increased
      extracellular GRN levels. In summary, we identified significant association of a
      locus on chromosome 1p13.3 with plasma GRN levels through an unbiased genome-wide
      screening approach and implicated SORT1 as an important regulator of GRN levels.
      This finding opens avenues for future research into GRN biology and the
      pathophysiology of neurodegenerative diseases.

PMID- 21087765
TI  - Comorbid major depression in obsessive-compulsive disorder patients.
AB  - Although major depressive disorder (MDD) has been consistently considered the
      most frequent complication of obsessive-compulsive disorder (OCD), little is
      known about the clinical characteristics of patients with both disorders. This
      study assessed 815 Brazilian OCD patients using a comprehensive psychiatric
      evaluation. Clinical and demographic variables, including OCD symptom dimensions,
      were compared among OCD patients with and without MDD. Our findings showed that
      prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for
      both sexes in this study. In addition, patients with comorbid MDD had higher
      severity scores of OCD symptoms. There was no preferential association of MDD
      with any particular OCD symptom dimension. This study supports the notion that
      depressed OCD patients present more severe general psychopathology.

PMID- 21087767
TI  - Associations between maternal characteristics and pregnancy-related stress among
      low-risk mothers: an observational cross-sectional study.
AB  - BACKGROUND: Pregnancy is viewed as a major life event and, while the majority of
      healthy, low-risk women adapt well to pregnancy, there are those whose levels of
      stress are heightened by the experience. OBJECTIVES: To determine the level of
      pregnancy-related stress experienced by a group of healthy, low-risk pregnant
      women and to relate the level of stress with a number of maternal
      characteristics. DESIGN: An observational cross-sectional study. SETTING: A
      large, urban maternity centre in Northern Ireland. PARTICIPANTS: Of the 306
      pregnant women who were invited to participate, 278 provided informed consent and
      were administered one self-complete questionnaire. Due to the withdrawal
      criteria, 15 questionnaires were removed from the analysis, resulting in a final
      sample of 263 healthy, low-risk pregnant women. METHODS: Levels of stress were
      measured using a self-report measure designed to assess specific worries and
      concerns relating to pregnancy. Maternal characteristics collected included age,
      marital status, social status, parity, obstetric history, perceived health status
      and 'wantedness' for the pregnancy. Regression analysis was undertaken using an
      ordinary linear regression model. RESULTS: The mean prenatal distress score in
      the sample was 15.1 (SD=7.4; range 0-46). The regression model showed that women
      who had had previous pregnancies, with or without complications, had
      significantly lower mean prenatal distress scores than primiparous women
      (p<0.01). Women reporting poorer physical health had higher mean prenatal
      distress scores than those who reported at least average health, while women aged
      16-20 experienced a mean increase in the reported prenatal distress score
      (p<0.05) in comparison to the reference group of 36 years and over. CONCLUSIONS:
      This study brings to light the prevalence of pregnancy-related stress within a
      sample representative of healthy, low-risk women. Current antenatal care is ill
      equipped to identify women suffering from high levels of stress; yet a growing
      body of research evidence links stress with adverse pregnancy outcomes. This
      study emphasises that healthy, low-risk women experience a range of pregnancy
      related stress and identification of stress levels, either through the use of a
      simple stress measurement tool or through the associated factors identified
      within this research study, provides valuable data on maternal well-being.

PMID- 21087768
TI  - Mechanical properties of bovine pia-arachnoid complex in shear.
AB  - Traumatic brain injury (TBI) has become a major public health and socioeconomic
      problem that affects 1.5 million Americans annually. Finite element methods have
      been widely used to investigate TBI mechanisms. The pia-arachnoid complex (PAC)
      covering the brain plays an important role in the mechanical response of the
      brain during impact or inertial loading. Existing finite element brain models
      have tended to oversimplify the response of the PAC due to a lack of accurately
      defined material properties of this structure, possibly resulting in a loss of
      accuracy in the model predictions. The objectives of this study were to
      experimentally determine the material properties of the PAC under shear loading.
      Bovine PAC was selected in the current study in view of its availability and
      comparability with previous studies. Tangential shear tests were conducted at
      0.8, 7.3, and 72 s(-1). The mean shear moduli were 11.73, 20.04, and 22.37 kPa at
      the three strain rates tested. The ultimate stress, at the three strain rates,
      was 9.21, 17.01, and 22.26 kPa, while the ultimate strain was 1.52, 1.58, and
      1.81. Results from the current study provide essential information to properly
      model the PAC membrane, an important component in the skull/brain interface, in a
      computational model of the human/animal head. Such an improved representation of
      the in vivo skull/brain interface will enhance future studies investigating brain
      injury mechanisms under various loading conditions.

PMID- 21087769
TI  - Mechanical force characterization in manipulating live cells with optical
      tweezers.
AB  - Laser trapping with optical tweezers is a noninvasive manipulation technique and
      has received increasing attentions in biological applications. Understanding
      forces exerted on live cells is essential to cell biomechanical
      characterizations. Traditional numerical or experimental force measurement
      assumes live cells as ideal objects, ignoring their complicated inner structures
      and rough membranes. In this paper, we propose a new experimental method to
      calibrate the trapping and drag forces acted on live cells. Binding a micro
      polystyrene sphere to a live cell and moving the mixture with optical tweezers,
      we can obtain the drag force on the cell by subtracting the drag force on the
      sphere from the total drag force on the mixture, under the condition of extremely
      low Reynolds number. The trapping force on the cell is then obtained from the
      drag force when the cell is in force equilibrium state. Experiments on numerous
      live cells demonstrate the effectiveness of the proposed force calibration
      approach.

PMID- 21087766
TI  - A review of diffusion tensor magnetic resonance imaging computational methods and
      software tools.
AB  - In this work we provide an up-to-date short review of computational magnetic
      resonance imaging (MRI) and software tools that are widely used to process and
      analyze diffusion-weighted MRI data. A review of different methods used to
      acquire, model and analyze diffusion-weighted imaging data (DWI) is first
      provided with focus on diffusion tensor imaging (DTI). The major preprocessing,
      processing and post-processing procedures applied to DTI data are discussed. A
      list of freely available software packages to analyze diffusion MRI data is also
      provided.

PMID- 21087770
TI  - Fast high-throughput method for the determination of acidity constants by
      capillary electrophoresis. II. Acidic internal standards.
AB  - A fast method for the determination of acidity constants by CZE has been recently
      developed. This method is based on the use of an internal standard of pK(a)
      similar to that of the analyte. In this paper we establish the reference pK(a)
      values of a set of 24 monoprotic neutral acids of varied structure that we
      propose as internal standards. These compounds cover the most usual working pH
      range in CZE and facilitate the selection of adequate internal standards for a
      given determination. The reference pK(a) values of the acids have been
      established by the own internal standard method, i.e. from the mobility
      differences between different acids of similar pK(a) in the same pH buffers. The
      determined pK(a) values have been contrasted to the literature pK(a) values and
      confirmed by determination of the pK(a) values of some acids of the set by the
      classical CE method. Some systematic deviations of mobilities have been observed
      in NaOH buffer in reference to the other used buffers, overcoming the use of NaOH
      in the classical CE method. However, the deviations affect in a similar degree to
      the test compounds and internal standards allowing thus, the use of NaOH buffer
      in the internal standard method. This fact demonstrates the better performance of
      the internal standard method over the classical method to correct mobility
      deviations, which together with its fastness makes it an interesting method for
      the routine determination of accurate pK(a) values of new pharmaceutical drugs
      and drug precursors.

PMID- 21087771
TI  - Exploring the fatty acids of vernix caseosa in form of their methyl esters by off
      line coupling of non-aqueous reversed phase high performance liquid
      chromatography and gas chromatography coupled to mass spectrometry.
AB  - Vernix caseosa is a greasy biofilm formed on the skin of the human fetus in the
      last period of pregnancy. This matrix is known to contain a range of uncommon
      branched chain fatty acids. In this study, we studied the fatty acid composition
      of vernix caseosa by non-aqueous reversed phase high performance liquid
      chromatography (RP-HPLC) fractionation followed by gas chromatography-electron
      ionization mass spectrometry (GC/EI-MS) of the fractions. For this purpose the
      fatty acids from vernix caseosa were converted into the corresponding methyl
      esters. These were fractionated by non-aqueous RP-HPLC using three serially
      connected C(18)-columns and pure methanol as the eluent. Aliquots of the HPLC
      fractions were directly analyzed by GC/EI-MS in the selected ion monitoring mode.
      Data analysis and visualization were performed by the creation of a two
      dimensional (2D) contour plot, in which GC retention times were plotted against
      the HPLC fractions. Inspection of the plot resulted in the detection of 133
      different fatty acids but only 16 of them contributed more than 1% to the total
      fatty acids detected. Identification was based on HPLC and GC retention data,
      GC/MS-SIM and full scan data, as well as plotting the logarithmic retention times
      against the longest straight carbon chain. In selected cases, aliquots of the
      HPLC fractions were hydrogenated or studied by means of the picolinyl esters.
      Using these techniques, the number of double bonds could be unequivocally
      assigned to all fatty acids. Moreover, the number of methyl branches, and in many
      cases the positions of methyl branches could be determined. The enantioselective
      analysis of chiral anteiso-fatty acids resulted in the dominance of the S
      enantiomers. However, high proportions of R-a13:0, R-a15:0, and R-a17:1 were also
      detected while a17:0 was virtually S-enantiopure.

PMID- 21087772
TI  - Structure and reactivity of the calcite-water interface.
AB  - The zetapotential of calcite in contact with aqueous solutions of varying
      composition is determined for pre-equilibrated suspensions by means of
      electrophoretic measurements and for non-equilibrium solutions by means of
      streaming potential measurements. Carbonate and calcium are identified as charge
      determining ions. Studies of the equilibrium solutions show a shift of
      isoelectric point with changing CO(2) partial pressure. Changes in pH have only a
      weak effect in non-equilibrium solutions. The surface structure of (104)-faces of
      single crystal calcite in contact to solutions corresponding to those of the
      zetapotential investigations is determined from surface diffraction measurements.
      The results reveal no direct indication of calcium or carbonate inner-sphere
      surface species. The surface ions are found to relax only slightly from their
      bulk positions; the most significant relaxation is a ~4 degrees  tilt of the
      surface carbonate ions towards the surface. Two ordered layers of water molecules
      are identified, the first at 2.35+/-0.05A above surface calcium ions and the
      second layer at 3.24+/-0.06A above the surface associated with surface carbonate
      ions. A Basic-Stern surface complexation model is developed to model observed
      zetapotentials, while only considering outer-sphere complexes of ions other than
      protons and hydroxide. The Basic-Stern SCM successfully reproduces the
      zetapotential data and gives reasonable values for the inner Helmholtz
      capacitance, which are in line with the Stern layer thickness estimated from
      surface diffraction results.

PMID- 21087773
TI  - Fluorescence of commercial Pluronic F127 samples: Temperature-dependent
      micellization.
AB  - We present a novel approach of using the butylated hydroxytoluene (BHT)
      antioxidant found in commercial Pluronic F127 samples as a marker of polymer
      aggregation. The BHT marker was compared to the pyrene dye and static light
      scattering methods as a way to measure the critical micelle concentration (CMC)
      and critical micelle temperature (CMT). The n->pi(*) transitions of BHT are
      sensitive to the microenvironment as demonstrated by plotting the fractional
      intensities of its excitation (~280nm) and emission (~325nm) peaks. BHT is more
      sensitive to changes in temperature than concentration. The partition coefficient
      increases ~40-fold for pyrene compared to ~2-fold for BHT when the temperature is
      increased from 25 to 37 degrees C. CMT values determined using the BHT
      fluorescence decrease with increasing F127 concentration. Our results show that
      BHT can be used as a reliable marker of changes in the microenvironment of
      Pluronic F127.

PMID- 21087774
TI  - Evaluating alternative electrostatic potential models for polyacrylamide-co
      acrylate in aqueous solution.
AB  - The capabilities of three simplified analytical equations to accurately model
      electrostatic interactions during proton binding and release by linear anionic
      polyelectrolytes in aqueous solution were evaluated. The impermeable sphere (IS),
      Donnan (DN), and cylindrical (CY) electrostatic models were fit to experimental
      acid-base titration curves of linear polyacrylamide-co-acrylate having ionizable
      site densities ranging from ca. 10-35%. The titrations were conducted in 0.003
      0.12M NaCl solutions and the sum of squared errors from modeled and experimental
      data was used as a comparative index of each model's capability. In addition, the
      relative size of each polyelectrolyte was estimated from its measured specific
      viscosity and then compared against the values obtained from the fitting
      procedure for the size parameter that each model contained. Although the IS and
      DN electrostatic models could be used to obtain reasonably good fits to each
      titration curve, the size parameter values obtained by each model were not
      reflective of the actual polyelectrolyte sizes, indicating that the models had
      limited physical meaning and that the size parameter was essentially just an
      additional fitting parameter in each model. In contrast, the CY model was not
      only more effective in its ability to fit the titration data but also provided a
      better physical representation of the polyelectrolyte size. Therefore, for
      polyelectrolytes that remain essentially linear or are only loosely coiled such
      that counter ions are free to travel throughout the polymer structure, we
      conclude that the CY model and its morphological representation of a cylindrical
      polyelectrolyte are more valid and realistic than the IS and DN models and their
      representation of polyelectrolytes as spheres.

PMID- 21087775
TI  - Are tones phones?
AB  - The psycholinguistic status of lexical tones and phones is indexed via
      phonological and tonological awareness (PA and TA, respectively) using Thai
      speech. In Experiment 1 (Thai participants, alphabetic script and
      orthographically explicit phones/tones), PA was better than TA in children and
      primary school-educated adults, and TA improved to PA levels only in tertiary
      educated adults. In Experiment 2 (Cantonese participants, logographic script and
      no orthographically explicit phones/tones), children and primary-educated adults
      had better PA than TA, and PA and TA were equivalent in tertiary-educated adults,
      but were nevertheless still below the level of their Thai counterparts.
      Experiment 3 (English-language participants, alphabetic script and nontonal)
      showed better PA than TA. Regression analyses showed that both TA and PA are
      predicted by reading ability for Thai children but by general nonorthographic age
      related variables for Cantonese children, whereas for English children reading
      ability predicts PA but not TA. The results show a phone>tone perceptual
      advantage over both age and languages that is affected by availability of
      orthographically relevant information and metalinguistic maturity. More
      generally, both the perception and the psycholinguistic representation of phones
      and tones differ.

PMID- 21087776
TI  - [Prevalence of obesity in pregnant women of Canary Islands, Spain].
AB  - BACKGROUND AND OBJECTIVE: Different epidemiological studies have shown that
      maternal excess of weight during pregnancy is associated with adverse outcomes of
      pregnancy, childbirth and morbidity of the neonate. Prevalence of obesity in a
      pregnant population of Canary Islands is reported here. SUBJECTS AND METHODS: The
      group studied was an integrated cohort of all the pregnant women being followed
      up at the Materno-Infant University Hospital of the Canarias [Hospital
      Universitario Materno-Infantil de Canarias; HUMIC] and who concluded their
      gestation during the year 2008 (n=6693). BMI was measured at the beginning of the
      pregnancy. RESULTS: 25.0% of the sample of pregnant women were overweight and
      17.1% were obese, increasing both with age and not influenced with the
      educational level. CONCLUSIONS: The prevalence of obesity and overweight among
      pregnant women from the Canary Islands is high. Among the values available from
      other European countries, only the UK reported values greater than our study
      sample.

PMID- 21087777
TI  - Similar to adiponectin, serum levels of osteoprotegerin are associated with
      obesity in healthy subjects.
AB  - An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes
      mellitus, the severity of vascular calcification, and coronary artery disease.
      Obesity is a risk factor for diabetes and cardiovascular disease, but little is
      known about the relationship between OPG and obesity. The purpose of this study
      was to determine if changes in body mass index (BMI) and insulin sensitivity
      influence circulating OPG in healthy subjects. A total of 100 subjects (36 lean,
      41 overweight, and 23 obese) with normal glucose tolerance, blood pressure, and
      electrocardiogram stress test result volunteered for this study. Insulin
      sensitivity was estimated using a 2-hour oral glucose tolerance test with oral
      glucose insulin sensitivity analysis. Osteoprotegerin, tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL),soluble receptor activator of nuclear
      factor-kappabeta ligand (sRANKL), and adiponectin were analyzed using
      commercially available enzyme-linked immunosorbent assays. Osteoprotegerin (P <
      .01) and adiponectin (P < .001) were significantly decreased in the obese
      compared with lean subjects. There was no significant difference between BMI
      categories for TRAIL or sRANKL. Controlling for age and sex, there was a
      significant correlation between OPG and adiponectin (r = 0.391, P < .001), BMI (r
      = -0.331, P < .001), waist circumference (r = -0.268, P < .01), homeostasis model
      assessment of insulin resistance (r = -0.222, P < .05), and oral glucose insulin
      sensitivity (r = 0.221, P < .05). Both OPG and adiponectin were negatively
      correlated with body weight, BMI, waist circumference, and fasting plasma insulin
      while being positively correlated with insulin sensitivity (P < .05). Controlling
      for age, sex, and BMI, TRAIL was positively related to fat mass (r = 0.373, P <
      .001) and waist circumference (r = 0.257, P < .05). In contrast to patients with
      type 2 diabetes mellitus, circulating OPG is lower in obese, but otherwise
      healthy subjects and is positively correlated with indices of insulin
      sensitivity.

PMID- 21087778
TI  - [A case of unilateral dislocation of C3 right facet joint treated with lateral
      mass plating].
AB  - Facet joint dislocations of the cervical spine are distractive-flexion injuries
      that account for 6 to 10 % of traumatic lesions of the subaxial cervical spine.
      Distractive-flexion injuries of the cervical spine were classified into four
      stages by Allen and Fergusson. These unstable lesions predominate at the fifth
      and sixth levels and all aspects of their management are subject to controversy,
      including their classification. Attempting reduction before surgery, performing
      MRI before or after closed reduction, choosing between surgery and external
      contention, the anterior versus the posterior approach are still matters of
      controversy between experts. The authors report a stage 2 distractive-flexion
      injury of the right facet joint of the third cervical vertebra treated by lateral
      mass plating as described by Roy-Camille (1995).

PMID- 21087779
TI  - [A case of cervical intradural extramedullary mature cystic teratoma: diagnosis
      and management].
AB  - Spinal intradural extramedullary teratoma is a rare condition that develops more
      commonly in children than in adults. It may be associated with spinal dysraphism.
      We report an exceptional case of adult-onset intradural extramedullary teratoma
      of the cervical spinal cord and bulbomedullary junction with no evidence of
      spinal dysraphism and no history of previous spinal surgery and/or lumbar
      puncture. The patient was a 38-year-old woman whose chief complaint was
      progressive installation of a tetraparesis. Magnetic resonance imaging showed a
      cystic tumor on both sides of the foramen magnum compressing the bulbomedullary
      junction. The tumor was totally surgically resected. The histopathological
      diagnosis was a mature teratoma.

PMID- 21087780
TI  - Purification and partial biochemical characterization of polyphenol oxidase from
      mamey (Pouteria sapota).
AB  - While a long shelf life for fruit products is highly desired, enzymatic browning
      is the main cause of quality loss in fruits and is therefore a main problem for
      the food industry. In this study polyphenol oxidase (PPO), the main enzyme
      responsible for browning was isolated from mamey fruit (Pouteria sapota) and
      characterized biochemically. Two isoenzymes (PPO 1 and PPO 2) were obtained upon
      ammonium sulfate precipitation and hydrophobic and ion exchange chromatography;
      PPO 1 was purified up to 6.6-fold with 0.28% yield, while PPO 2 could not be
      characterized as enzyme activity was completely lost after 24 h of storage. PPO 1
      molecular weight was estimated to be 16.1 and 18 kDa by gel filtration and SDS
      PAGE, respectively, indicating that the native state of the PPO 1 is a monomer.
      The optimum pH for PPO 1 activity was 7. The PPO 1 was determined to be maximum
      thermally stable up to 35 degrees C. Kinetic constants for PPO 1 were K(m)=44 mM
      and K(m)=1.3 mM using catechol and pyrogallol as substrate, respectively. The
      best substrates for PPO 1 were pyrogallol, 4-methylcatechol and catechol, while
      ascorbic acid and sodium metabisulfite were the most effective inhibitors.

PMID- 21087781
TI  - Detection of specific antibodies anti-Neospora caninum in the fallow deer (Dama
      dama).
AB  - Sera from 335 farmed fallow deer (Dama dama) at the breeding station in Kosewo
      Gorne in the Mazurian Lake District, North-East Poland, were investigated for the
      presence of antibodies against Neospora caninum. The distribution of age groups
      was as follow: >4 years - 154 animals; 2 years - 76 animals; 1 year - 105
      animals. Ten sera with the optical density exceeding 0.159 absorbance units
      (i.e., cut-off value) in ELISA test were also analyzed by Western blot. Western
      blot analysis revealed seroreactivity against immunodominant N. caninum antigens
      of 37, 25, and 16kDa; however, in some sera additional bands were also visible.
      This is the first screening studies for antibodies against N. caninum in farmed
      fallow deer in Poland, in the region where neosporosis was confirmed in cattle
      and in farmed and free-ranging European red deer (Cervus elaphus).

PMID- 21087782
TI  - [Movement disorders and neurometabolic diseases].
AB  - Movement disorders, especially dystonia, are a frequent manifestation of
      neurometabolic diseases. Proper characterization and classification of movement
      disorders is crucial but may be challenging in this setting. The diagnostic work
      up should be focused first on treatable disease. Mixed movement disorders, marked
      orofacial involvement and associated neurological and extra-neurological features
      should prompt the clinician to consider the possibility of an underlying
      neurometabolic disorder. The diagnostic approach is based on the abrupt,
      paroxysmal or insidious nature of onset of the movement disorders, the clinical
      picture including neurological and systemic signs and symptoms, and the presence
      or absence of abnormalities on the brain MRI. In addition to specific treatment
      for the metabolic disease, when available, symptomatic treatment of the movement
      disorders can be proposed, remembering that these patients are particularly
      vulnerability to iatrogenesis.

PMID- 21087783
TI  - [Autosomal recessive cerebellar ataxias].
AB  - INTRODUCTION: Autosomal recessive cerebellar ataxias (ARCA) are heterogeneous and
      complex inherited neurodegenerative diseases that may affect the cerebellum
      and/or the spinocerebellar tract, the posterior column of the spinal cord and the
      peripheral nerves. Cerebellar ataxia is frequently proeminent and mostly
      associated with several neurological or extra-neurological signs, leading to a
      major disability before the age of 30. STATE OF ART: Friedreich's ataxia (FRDA)
      is clearly the most frequent ARCA and several rarer entities have been described
      during the past fifteen years such as ataxia with oculomotor apraxia type 1
      (AOA1) and type 2 (AOA2), ataxia with vitamin E deficiency (AVED) and autosomal
      recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The ACAR are
      characterized by both allelic and non-allelic genetic heterogeneity. They may be
      divided into three groups: spino-cerebellar ataxia with pure sensory neuropathy;
      cerebellar ataxia with sensori-motor axonal neuropathy; pure cerebellar ataxia
      (i.e. ataxia of purely cerebellar origin that may be associated with other
      symptoms). Common physiological pathways are involved in several ARCA, such as
      DNA repair deficiency (AOA1, ataxia telangiectasia [AT]...), RNA termination
      disorder (AOA2), mitochondrial defect (FRDA, sensory ataxic neuropathy with
      dysarthria and ophthalmoplegia [Sando]...), lipoprotein assembly defects (AVED,
      abetalipoproteinemia [ABL]), chaperon protein disorders (ARSACS, Marinesco
      Sjogren syndrome [MSS]) or peroxysomal diseases (Refsum disease [RD]).
      PERSPECTIVES: New nanotechnology methods and high throughput gene analysis as
      well as bioinformatics should lead to the identification of several new ARCAs in
      the next few years despite the rarity of these entities. However, the challenge
      of the next decades will be the discovery of efficient treatments for these
      disabling neurodegenerative disorders. CONCLUSION: Clinicians should be aware of
      the more frequent ARCAs, especially FRDA, in addition to ARCAs for which
      treatment is available (FRDA, AVED, ABL and RD for instance).

PMID- 21087784
TI  - Opalski syndrome detected on DWI MRI: A rare lateral medullary infarction. Case
      report and review.
AB  - INTRODUCTION: Wallenberg's syndrome and ipsilateral paresis due to combined
      infarction of the lateral medullary and cervical spinal infarction is known as
      Opalski syndrome. This rarely described syndrome was reported, to our knowledge,
      with DWI MRI, only once. CASE REPORT: We report the case of a 43-year-old man
      with autosomal dominant polycystic kidney disease who, after a brief episode of
      coma, developed Wallenberg syndrome and ipsilateral hemiparesis. Initial
      diffusion weighted-imaging MRI showed a high-intensity signal involving the
      lateral medulla oblongata and the spinal cord; but FLAIR MRI sequences showed
      bilateral high-intensity signals in the lateral medulla oblongata and spinal cord
      and high-intensity signals in the right and left cerebellar hemisphere in the
      PICA territories. MRI performed one year later showed an infarction involving the
      left medullary area and adjacent spinal segments alone. CONCLUSION: This
      observation illustrates a rare syndrome of lateral medullary infarction,
      associated with spinal cord infarction related to a possible transient basilar
      occlusion.

PMID- 21087786
TI  - Estimation of the environmental risk posed by landfills using chemical,
      microbiological and ecotoxicological testing of leachates.
AB  - The leachates from 22 municipal solid waste (MSW) landfill sites in Southern
      Poland were characterized by evaluation of chemical, microbiological and
      ecotoxicological parameters. Chemical analyses were mainly focused on the
      identification of the priority hazardous substances according to Directive on
      Priority Substances, 2008/105/EC (a daughter directive of the WFD) in leachates.
      As showed, only five substances (Cd, Hg, hexachlorobutadiene, pentachlorobenzene
      and PAHs) were detected in the leachates. The compounds tested were absent or
      present at very low concentrations. Among them, only PAHs were found in all
      samples in the range from 0.057 to 77.2 MUg L-1. The leachates were contaminated
      with bacteria, including aerobic, psychrophilic and mesophilic bacteria, coliform
      and fecal coliforms, and spore-forming-bacteria, including Clostridium
      perfringens, and with filamentous fungi. From the analysis of specific
      microorganism groups (indicators of environmental pollution by pathogenic or
      opportunistic pathogenic organisms) it can be concluded that the landfill
      leachates showed sanitary and epidemiological hazard. In the ecotoxicological
      study, a battery of tests comprised of 5 bioassays, i.e. Microtox((r)), Spirotox,
      Rotoxkit FTM, Thamnotoxkit FTM and Daphtoxkit FTM magna was applied. The leachate
      samples were classified as toxic in 13.6%, highly toxic in 54.6% and very highly
      toxic in 31.8%. The Spirotox test was the most sensitive bioassay used. The
      percentage of class weight score was very high - above 60%; these samples could
      definitely be considered seriously hazardous and acutely toxic to the fauna and
      microflora. No correlations were found between the toxicity values and chemical
      parameters. The toxicity of leachate samples cannot be explained by low levels of
      the priority pollutants. It seems that other kinds of xenobiotics present in the
      samples at subacute levels gave the high aggregate toxic effect. The chemical,
      ecotoxicological and microbiological parameters of the landfill leachates should
      be analyzed together to assess the environmental risk posed by landfill
      emissions.

PMID- 21087785
TI  - Multiple retroviral infection by HTLV type 1, 2, 3 and simian foamy virus in a
      family of Pygmies from Cameroon.
AB  - To better understand the origins and modes of transmission of HTLV-3 and to
      search for other retroviral infections (HTLV-1, HTLV-2, foamy viruses), we
      studied the family of a HTLV-3-infected individual (Pyl43), from Cameroon. Thirty
      five persons were included. All adult men were still actively hunting nonhuman
      primates (NHP). All women were also butchering and cutting-up animals. Five
      persons reported a bite by an NHP. While HTLV-3 infection was only found in
      Pyl43, HTLV-1 and HTLV-2 infections were found, respectively, in 5 and 9 persons
      with one being co-infected by both retroviruses. Phylogenetic analysis suggested
      intra-familial transmission of HTLV-1 subtypes B and D and HTLV-2. One man was
      infected by a chimpanzee foamy virus, acquired probably 45 years ago, through a
      bite. Acquisition of retroviral infections still occurs in central Africa
      involving to various extent not only intra-familial transmission for HTLV-1/HTLV
      2 but also direct interspecies transmission from NHP for foamy virus and possibly
      for HTLV-1 and HTLV-3.

PMID- 21087787
TI  - Removal of estrogens through water disinfection processes and formation of by
      products.
AB  - Estrogens constitute a recognized group of environmental emerging contaminants
      which have been proven to induce estrogenic effects in aquatic organisms exposed
      to them. Low removal efficiency in wastewater treatment plants results in the
      presence of this type of contaminants in surface waters and also even in finished
      drinking water. This manuscript reviews the environmental occurrence of natural
      (estrone, estradiol and estriol) and synthetic (ethynyl estradiol) estrogens in
      different water matrices (waste, surface, ground and drinking water), and their
      removal mainly via chemical oxidative processes. Oxidative treatments have been
      observed to be very efficient in eliminating estrogens present in water; however,
      disinfection by-products (DBPs) are generated during the process.
      Characterization of these DBPs is essential to assess the risk that drinking
      water may potentially pose to human health since these DBPs may also have
      endocrine disrupting properties. This manuscript reviews the DBPs generated
      during oxidative processes identified so far in the literature and the
      estrogenicity generated by the characterized DBPs and/or by the applied
      disinfection technology.

PMID- 21087788
TI  - Prospective evaluation of longitudinal changes in human papillomavirus genotype
      and phylogenetic clade associated with cervical disease progression.
AB  - OBJECTIVE: Changes in the HPV genotype detected in patients over time could alter
      cervical disease progression. Identification of patterns in the alteration of HPV
      genotype should also be related to cytological and histological findings. Thus,
      we assessed the risk for low-grade squamous intraepithelial lesion (LSIL) or high
      grade SIL (HSIL)/squamous cell carcinoma (SCC) associated with alterations in the
      HPV genotype detected, presence of multiple HPV genotypes, and individual
      genotyping or HPV clade grouping. METHODS: The 1052 participants were monitored
      by HPV chip and Pap smear. We calculated odds ratios and applied sequential
      association analysis (SAA) and decision tree analysis (DTA). RESULTS: We
      classified HPV alteration as persistence, regression (spontaneous vs.
      therapeutic), or metatyping (progressive vs. regressive). Spontaneous regression
      occurred in 71.9% of patients. Metatyping was strongly associated with
      progression (RR: 3.9, p=0.0242), with progressive metatyping showing a higher
      risk of progression (RR: 31.49, p=0.00448). Few patients with multiple infections
      were identified in the initial screen but 30.8% of patients had multiple
      infections in the final analysis. HPV-16, -35, -52, and -58 were commonly
      associated with HPV persistence. Univariate analysis determined that final
      diagnosis significantly associated with HPV type at the endpoint (p<0.0001),
      persistence (p=0.0001), and progressive metatyping (p=0.0022). SAA determined
      that HPV-66, -68, and -69 were significantly associated with HSIL, and HPV-16 and
      -18 persistence significantly association with SCC. DTA indicated an age less
      than 28 years had a peak in LSIL, and an age between 32 and 48 years had a peak
      in HSIL. A bimodal peak in SCC for HR-2 at the endpoint was observed in
      participants less than 32 and greater than 48 years of age. CONCLUSIONS: The
      alteration patterns of HPV infection detected included persistence, regression,
      and metatyping. HPV persistence and progressive metatyping are significant
      signatures of disease progression.

PMID- 21087789
TI  - The incorporation of casein phosphopeptide-amorphous calcium phosphate into a
      glass ionomer cement.
AB  - OBJECTIVES: The aim of this study was to measure the effect of incorporating CPP
      ACP into an autocure GIC on physical and mechanical properties, ion release and
      enamel demineralization inhibition. METHODS: Physical and mechanical properties
      were evaluated using tests specified by the International Organization for
      Standardization (ISO). Concentrations of fluoride, calcium and inorganic
      phosphate in deionized water (pH 6.9) and lactic acid (pH 4.8) were measured up
      to five months. Cavities on human extracted molars were prepared, restored with
      GIC (control), CPP-ACP modified GIC or resin composite, then stored in 50mM
      lactic acid solution at pH 4.8 for 4 days. Sections of demineralized enamel were
      examined using polarized light microscopy followed by lesion area measurement.
      RESULTS: The incorporation of up to 5% CPP-ACP into Fuji VII decreased the
      cements' strength and prolonged setting time. However, values remained within ISO
      limits. The incorporation of 3 or 5% CPP-ACP significantly decreased fluoride
      release, while higher calcium and inorganic phosphate release occurred. The
      demineralized enamel area adjacent to GIC with 3 or 5% CPP-ACP was significantly
      smaller compared to GIC control. SIGNIFICANCE: The incorporation of 3% CPP-ACP
      into GIC has the potential to improve its anticariogenic ability without
      adversely affecting its mechanical properties.

PMID- 21087790
TI  - The galanin peptide family in inflammation.
AB  - The immune system defends the organism against invading pathogens. In recent
      decades it became evident that elimination of such pathogens, termination of
      inflammation, and restoration of host homeostasis all depend on bidirectional
      crosstalk between the immune system and the neuroendocrine system. This crosstalk
      is mediated by a complex network of interacting molecules that modulates
      inflammation and cell growth. Among these mediators are neuropeptides released
      from neuronal and non-neuronal components of the central and peripheral nervous
      systems, endocrine tissues, and cells of the immune system. Neuropeptide
      circuitry controls tissue inflammation and maintenance, and an imbalance of pro-
      and anti-inflammatory neuropeptides results in loss of host homeostasis and
      triggers inflammatory diseases. The galanin peptide family is undoubtedly
      involved in the regulation of inflammatory processes, and the aim of this review
      is to provide up-to-date knowledge from the literature concerning the regulation
      of galanin and its receptors in the nervous system and peripheral tissues in
      experimental models of inflammation. We also highlight the effects of galanin and
      other members of the galanin peptide family on experimentally induced
      inflammation and discuss these data in light of an anti-inflammatory role for
      this family of peptides.

PMID- 21087792
TI  - Introduction to an occasional series.

PMID- 21087791
TI  - Evaluation of TET2 deletions in myeloid disorders: a fluorescence in situ
      hybridization analysis of 109 cases.
AB  - Alterations of the ten-eleven translocation-2 (TET2) gene have been recently
      identified in patients with myeloid malignancies using molecular, comparative
      genomic hybridization and single nucleotide polymorphism array techniques. We
      have performed TET2 fluorescence in situ hybridization analysis in a cohort of
      patients with myeloid disorders including myeloid malignancies and chronic
      idiopathic neutropenia, aiming to determine the usefulness of the technique in
      the identification of TET2 gene alterations. A TET2 deletion was found in one
      patient with chronic myelomonocytic leukemia suggesting that fluorescence in situ
      hybridization may have a role in identification of TET2 deletions, at least in
      this group of patients.

PMID- 21087793
TI  - Absence of mutations of the histone methyltransferase gene EZH2 in splenic b-cell
      marginal zone lymphoma.

PMID- 21087794
TI  - Genotoxicity of 4-nonylphenol and nonylphenol ethoxylate mixtures by the use of
      Saccharomyces cerevisiae D7 mutation assay and use of this text to evaluate the
      efficiency of biodegradation treatments.
AB  - Nonylphenol ethoxylates (NPnEOs, where n is the number of ethoxylic units in the
      molecule) are non-ionic surfactants widely used for domestic and industrial
      purposes. 4-Nonylphenol (4-NP), the main product of NPnEO biodegradation, is a
      toxic xenobiotic compound classified as endocrine disrupter. While numerous
      studies reported the toxicity and oestrogenic activity of nonylphenols, little is
      known about the mutagenicity of these compounds. In this paper, the genotoxicity
      of 4-NP and NPnEO mixtures was evaluated by using the D7 strain of Saccharomyces
      cerevisiae as experimental model. The same genotoxicity tests were applied to
      effluents deriving from experimental packed-bed bioreactors, developed for the
      treatment of NPnEO contaminated wastewater, in order to evaluate the residual
      genotoxic potential with respect to the influent waste. The target compounds fed
      to the bioreactors were 4-NP and NPnEO mixtures possessing an average of 5 or 1.5
      ethoxylic units (Igepal CO-520 and Igepal CO-210, respectively). The results
      showed that 4-NP induced significant cytotoxic effect on S. cerevisiae cells at
      50 mg/L, as well as mutagenic effects at the lowest tested concentrations (12 and
      25 mg/L). 4-NP was the most genotoxic compound among those assayed, followed by
      Igepal CO-210, whereas Igepal CO-520 did not induce genotoxicity at any of the
      assayed concentrations. The genotoxic effects of 4-NP on yeast cells disappeared
      after the treatment of 4-NP artificially contaminated water in the bioreactor.
      This indicates that the biological treatment is capable of removing not only the
      pollutant, but also the toxicity associated to the compound and its degradation
      metabolites. This study represents, to the best of our knowledge, the first
      report that evaluates the genotoxicity of both 4-NP, NPnEOs and their potential
      aerobic degradation products on an eukaryotic organism. The obtained results
      suggest that the S. cerevisiae D7 strain is a very effective model microorganism
      to study the induction of genotoxic damage by the compounds under study.
      Moreover, this yeast assay has been proved effective to evaluate the
      detoxification effect deriving from biotreatment processes.

PMID- 21087795
TI  - Water pollution in Pakistan and its impact on public health--a review.
AB  - Water pollution is one of the major threats to public health in Pakistan.
      Drinking water quality is poorly managed and monitored. Pakistan ranks at number
      80 among 122 nations regarding drinking water quality. Drinking water sources,
      both surface and groundwater are contaminated with coliforms, toxic metals and
      pesticides throughout the country. Various drinking water quality parameters set
      by WHO are frequently violated. Human activities like improper disposal of
      municipal and industrial effluents and indiscriminate applications of
      agrochemicals in agriculture are the main factors contributing to the
      deterioration of water quality. Microbial and chemical pollutants are the main
      factors responsible exclusively or in combination for various public health
      problems. This review discusses a detailed layout of drinking water quality in
      Pakistan with special emphasis on major pollutants, sources of pollution and the
      consequent health problems. The data presented in this review are extracted from
      various studies published in national and international journals. Also reports
      released by the government and non-governmental organizations are included.

PMID- 21087796
TI  - Morphine decreases early peritoneal innate immunity responses in Swiss-Webster
      and C57BL6/J mice through the inhibition of mast cell TNF-alpha release.
AB  - OBJECTIVE: To characterize immunosuppressive effects of morphine on the early
      innate immunity response of cytokine production in peritoneal cavity after LPS
      challenge. METHODS: The effects of a single i.p. administration of morphine (3.1
      or 31 mg/kg) on LPS-induced tumor necrosis factor alpha (TNF-alpha) and monocyte
      chemoattractant protein-1 (CCL2) intraperitoneal release was tested in Swiss
      Webster, C57BL/6J, mast cell deficient Kit(Wsh/Wsh) (W-sh) and mast cell
      reconstituted (W-sh-rec) mice. RESULTS: Morphine was found to inhibit LPS-induced
      TNF-alpha but not CCL2 release in the peritoneal cavity. Studies on mast cell
      deficient and reconstituted mice indicate that resident mast cells mediate
      selective morphine immunosuppression in the peritoneal cavity.

PMID- 21087797
TI  - Gene biomarkers in diatom Thalassiosira pseudonana exposed to polycyclic aromatic
      hydrocarbons from contaminated marine surface sediments.
AB  - Marine diatoms have a key role in the global carbon fixation and therefore in the
      ecosystem. We used Thalassiosira pseudonana as a model organism to assess the
      effects of exposure to environmental pollutants at the gene expression level.
      Diatoms were exposed to polycyclic aromatic hydrocarbons mixture (PAH) from
      surface sediments collected at a highly PAH contaminated area of the
      Mediterranean Sea (Genoa, Italy), due to intense industrial and harbor
      activities. The gene expression data for exposure to the sediment-derived PAH
      mixture was compared with gene expression data for in vitro exposure to specific
      polycyclic aromatic hydrocarbons. The data shows that genes involved in stress
      response, silica uptake, and metabolism were regulated both upon exposure to the
      sediment-derived PAH mixture and to the single component. Complementary
      monitoring of silica in the diatom cultures provide further evidence of a reduced
      cellular uptake of silica as an end-point for benzo[a]pyrene exposure that could
      be linked with the reduced gene and protein expression of the silicon transporter
      protein. However some genes showed differences in regulation indicating that
      mixtures of structurally related chemical compounds can elicit a slightly
      different gene expression response compared to that of a single component. The
      paper provides indications on the specific pathways affected by PAH exposure and
      shows that selected genes (silicon transporter, and silaffin 3) involved in
      silica uptake and metabolism could be suitable molecular biomarkers of exposure
      to PAHs.

PMID- 21087798
TI  - Active bio-monitoring of contamination in aquatic systems--an in situ
      translocation experiment applying the PICT concept.
AB  - The environmental risk assessment of toxicants is often derived from chemical
      monitoring, based on single species tests performed in the laboratory. However,
      to provide ecologically relevant information, community approaches are required.
      The aim of this study was to causally link prometryn exposure to community-level
      effects in complex field situations and to identify response times of adaptation
      to pollution and recovery from pollution. For this reason sensitivity shifts in
      communities were detected and related to structural changes within the periphyton
      community. Furthermore, it was intended to illustrate the possibility of a
      combined approach of community translocation and sensitivity assessment for
      active monitoring of polluted sites. Periphyton was grown at a reference (R) and
      at a polluted (P) site of the river Elbe basin for 26 days, was subsequently
      transferred from the polluted site to the reference site and vice versa.
      Sensitivity of communities to prometryn was determined according to the pollution
      induced community tolerance (PICT)-concept in short-term tests by measuring
      photosynthesis inhibition and was related to structural changes in algal class
      and diatom species composition. Exposure to prometryn was determined using polar
      organic integrative samplers (POCIS), giving time-weighted average
      concentrations. Environmental concentrations of prometryn were significantly
      higher at the polluted site compared to the reference site. Communities grown at
      the polluted site showed a higher tolerance to prometryn in comparison to the
      reference site. 17 Days after the translocation to the reference site, EC(50)
      decreased 2-fold compared to the non-translocated P-community of the same age. By
      contrast, EC(50) of the community grown at the reference site was 5 times higher
      after 17 days exposure at the polluted site. Furthermore, P-R communities were
      less sensitive to prometryn (higher EC(50)) than R-P communities, 24 days after
      translocation. These changes in sensitivity to prometryn were consistent with
      changes in species composition and clearly indicate that the exposure history of
      communities is defining the time-response of recovery and adaptation. In
      conclusion, the PICT-concept is shown to be a suitable tool for analysis of
      recovery and adaptation processes of communities under natural conditions.
      Therefore, it improves the link between cause and effect in field situations. In
      situ translocation studies provide an ecological relevant assessment of pesticide
      effects under field conditions and could be used as a diagnostic tool in active
      monitoring for decision-making frameworks as used in the implementation of the
      European Water Framework Directive (WFD).

PMID- 21087799
TI  - A new kaolin-based hemostatic bandage use after coronary diagnostic and
      interventional procedures.
AB  - BACKGROUND: Bleeding and vascular access site complications are an important
      cause of morbidity after percutaneous femoral procedures. Together with collagen
      based and suture-based vascular closure devices, new hemostatic dressings have
      been developed to control heavy bleeding. AIM OF STUDY: To evaluate safety and
      efficacy results of the first clinical QuikClot Interventional Hemostatic Bandage
      use for femoral artery closure after diagnostic or interventional procedures.
      METHODS: The first European safety study was performed at the Centro Cardiologico
      Monzino in Milan, Italy, on January 2010. Forty consecutive patients (75% male,
      mean age 68 +/- 11years) undergoing diagnostic angiography (62%) or PCI (38%) by
      femoral approach with a 6- (90%) or 7-Fr (10%) size introducer, received arterial
      sheath removal with the QuikClot Interventional gauze use. The mean ACT value at
      hemostasis time was 138 +/- 24s (range 95-186s). Hemostasis was achieved in a
      mean time of 4.9 +/- 0.5 min. Only one hemostasis failure occurred requiring
      prolonged mechanical compression. Neither major bleeding, re-bleeding nor
      hematoma occurred after early (4h after procedure) ambulation. CONCLUSIONS:
      QuikClot Interventional Bandage obtained prompt hemostasis and allowed for an
      early ambulation without clinical complications.

PMID- 21087800
TI  - Circular permutation: a different way to engineer enzyme structure and function.
AB  - Protein engineers traditionally rely on amino acid substitutions to alter the
      functional properties of biomacromolecules, yet have largely overlooked the
      potential benefits of reorganizing the polypeptide chain of a protein by circular
      permutation (CP). By connecting the native protein termini via a covalent linker
      and introducing new ends through the cleavage of an existing peptide bond, CP can
      perturb local tertiary structure and protein dynamics, as well as introduce
      possible quaternary structure changes. In several recent studies, these effects
      have successfully been exploited to manipulate protein scaffolds, resulting in
      improved catalytic activity and altered substrate or ligand binding affinity, as
      well as enabling the design of novel biocatalysts and biosensors.

PMID- 21087801
TI  - Radiation Oncology Safety Information System (ROSIS)--profiles of participants
      and the first 1074 incident reports.
AB  - BACKGROUND AND PURPOSE: The Radiation Oncology Safety Information System (ROSIS)
      was established in 2001. The aim of ROSIS is to collate and share information on
      incidents and near-incidents in radiotherapy, and to learn from these incidents
      in the context of departmental infrastructure and procedures. MATERIALS AND
      METHODS: A voluntary web-based cross-organisational and international reporting
      and learning system was developed (cf. the www.rosis.info website). Data is
      collected via online Department Description and Incident Report Forms. A total of
      101 departments, and 1074 incident reports are reviewed. RESULTS: The ROSIS
      departments represent about 150,000 patients, 343 megavoltage (MV) units, and 114
      brachytherapy units. On average, there are 437 patients per MV unit, 281 per
      radiation oncologist, 387 per physicist and 353 per radiation therapy
      technologist (RT/RTT). Only 14 departments have a completely networked system of
      electronic data transfer, while 10 departments have no electronic data transfer.
      On average seven quality assurance (QA) or quality control (QC) methods are used
      at each department. A total of 1074 ROSIS reports are analysed; 97.7% relate to
      external beam radiation treatment and 50% resulted in incorrect irradiation. Many
      incidents arise during pre-treatment but are not detected until later in the
      treatment process. Where an incident is not detected prior to treatment, an
      average of 22% of the prescribed treatment fractions were delivered incorrectly.
      The most commonly reported detection methods were "found at time of patient
      treatment" and during "chart-check". CONCLUSION: While the majority of the
      incidents that reported to this international cross-organisational reporting
      system are of minor dosimetric consequence, they affect on average more than 20%
      of the patient's treatment fractions. Nonetheless, defence-in-depth is apparent
      in departments registered with ROSIS. This indicates a need for further
      evaluation of the effectiveness of quality controls.

PMID- 21087802
TI  - Listeria monocytogenes in Irish Farmhouse cheese processing environments.
AB  - Sixteen cheesemaking facilities were sampled during the production season at
      monthly intervals over a two-year period. Thirteen facilities were found to have
      samples positive for Listeria monocytogenes. Samples were divided into 4
      categories; cheese, raw milk, processing environment and external to the
      processing environment (samples from the farm such as silage, bedding, and pooled
      water). In order to attempt to identify the source, persistence and putative
      transfer routes of contamination with the L. monocytogenes isolates, they were
      differentiated using PFGE and serotyping. Of the 250 isolates, there were 52
      different pulsotypes. No pulsotype was found at more than one facility. Two
      facilities had persistent pulsotypes that were isolated on sampling occasions at
      least 6 months apart. Of the samples tested, 6.3% of milk, 13.1% of processing
      environment and 12.3% of samples external to the processing environment,
      respectively, were positive for L. monocytogenes. Pulsotypes found in raw milk
      were also found in the processing environment, however, one of the pulsotypes
      from raw milk was found in cheese on only one occasion. One of the pulsotypes
      isolated from the environment external to the processing facility was found on
      the surface of cheese, however, a number of them were found in the processing
      environment. The results suggest that the farm environment external to the
      processing environment may in some cases be the source of processing environment
      contamination with L. monocytogenes.

PMID- 21087803
TI  - Anemia--the overlooked factor in bleeding related to liver disease.

PMID- 21087804
TI  - TGF-beta1 mediated activation of Rho kinase induces TGF-beta2 and endothelin-1
      expression in human hepatic stellate cells.
AB  - BACKGROUND & AIMS: TGF-beta1 a key pro-fibrotic factor activates signaling via
      the canonical ALK/SMAD as well as the Rho GTPase pathways. Rho kinase is a major
      downstream effector of Rho GTPase signaling. To understand the contribution of
      Rho kinase activation towards the synthesis of fibrotic mediators by hepatic
      stellate cells (HSC), we first profiled activated HSC and fibrotic liver tissues
      to identify common transcripts that were most significantly up-regulated across
      all samples. We then applied a pharmacologic as well as a genomics approach in a
      TGF-beta1 activated human HSC line (LX-2) to study the involvement of Rho kinase
      signaling in the expression of a subset of these up-regulated fibrotic genes.
      METHODS: Total RNA was profiled using microarray chips. Data analysis was
      performed using Ingenuity Pathway Analysis software. LX-2 cells were activated
      with 10 ng/ml of TGF-beta1 for 24 h. Activation of downstream pathways was
      assessed by Western blotting with phospho-specific target biomarker antibodies.
      Targeted knockdown of Rho kinase isoforms 1 and 2 was achieved with RNAi.
      Secreted levels of endothelin-1, TGF-beta2, and thrombospondin-1 were measured by
      ELISA. RESULTS: TGF-beta1 activated Rho kinase and Smad pathways in LX-2 cells.
      The syntheses of endothelin-1 and TGF-beta2 were significantly inhibited in TGF
      beta1 treated LX-2 cells, by isoform non-selective Rho kinase inhibitors. siRNA
      knockdown of each isoform suggested that endothelin-1 synthesis was largely
      mediated by the Rho kinase-1 isoform, while both isoforms contributed to the
      synthesis of TGF-beta2. CONCLUSIONS: The TGF-beta1 mediated secretion of
      endothelin-1 and TGF-beta2 is mediated by Rho kinase activation in human HSC.

PMID- 21087805
TI  - Obliterative portal venopathy: portal hypertension is not always present at
      diagnosis.
AB  - BACKGROUND & AIMS: Previous studies on obliterative portal venopathy (OPV) have
      been biased due to the selection of patients with non-cirrhotic portal
      hypertension. The aim of this study was to clarify the characteristics of OVP
      diagnosed by liver biopsy. METHODS: Fifty-nine consecutive patients with OPV were
      retrospectively selected on strict histological criteria. Clinical, laboratory,
      portal vein patency, and associated disorders potentially involving vascular
      alterations were analyzed. The occurrence of complications was recorded during
      follow-up. RESULTS: Mean age at diagnosis was 38.5+/-15 years old. Initial
      presentation was portal hypertension (64% of patients) and/or extrahepatic portal
      vein thrombosis (EHPVT) (22%) or isolated abnormal laboratory tests (20%).
      Associated diseases found at diagnosis were: prothrombotic disorders (30% of
      patients) and immune-mediated disorders (17%); 53% of patients had no causal
      factor (idiopathic OPV). During follow-up (median 8.6 years, range 1-23 years),
      features of portal hypertension worsened in 46% of patients; EHPVT and portal
      hypertension were finally found in 44% and 88% of patients. Anti-coagulation and
      beta-blockers were administered in 47% and 59% of patients, respectively. Severe
      complications (liver transplantation and/or death) occurred in 11 (19%) patients,
      8 had idiopathic OPV. Patients with prothrombotic disorders received earlier
      anticoagulation therapy; all survived without transplantation. CONCLUSIONS: A
      confident diagnosis of OPV can be done by biopsy and is conceivable in patients
      under 40 years without clinically significant portal hypertension. Poor outcome
      was noted in 19% of patients, most of them affected with idiopathic OPV. Patients
      with prothrombotic disorders received early anticoagulation and appeared to have
      a better outcome despite a high proportion of EHPVT.

PMID- 21087806
TI  - First-line assessment of patients with chronic liver disease with non-invasive
      techniques and without recourse to liver biopsy.

PMID- 21087807
TI  - Focus.

PMID- 21087808
TI  - The social side of Homo economicus.
AB  - Many recent experiments in the field of behavioural economics appear to
      demonstrate a willingness of humans to behave altruistically, even when it is not
      in their interest to do so. This has led to the assertion that humans have
      evolved a special predisposition towards altruism. Recent studies have questioned
      this, and demonstrated that selfless cooperation does not hold up in controlled
      experiments. As I discuss here, this calls for more economic 'field experiments'
      and highlights the need for greater integration of the evolutionary and economic
      sciences.

PMID- 21087809
TI  - Blebbing dynamics during endothelial cell spreading.
AB  - Cell spreading is a critical component of numerous physiological phenomena
      including cancer metastasis, embryonic development, and mitosis. We have
      previously illustrated that cellular blebs appear after abrupt cell-substrate
      detachment and play a critical role in regulating membrane tension; however, the
      dynamics of bleb-substrate interactions during spreading remains unclear. Here we
      explore the role of blebs during endothelial cell spreading using chemical and
      osmotic modifications to either induce or inhibit bleb formation. We track cell
      substrate dynamics as well as individual blebs using surface sensitive
      microscopic techniques. Blebbing cells (both control and chemically induced)
      exhibit increased lag times prior to fast growth. Interestingly, lamellae appear
      later for blebbing compared to non-blebbing cells, and in all cases, lamellae
      signal the start of fast spreading. Our results indicate that cellular blebs play
      a key role in the early stage of cell spreading, first by controling the initial
      cell adhesion and then by presenting a dynamic inhibition of cell spreading until
      a lamella appears and fast spreading ensues.

PMID- 21087810
TI  - Identification of a novel heteroglycan-interacting protein, HIP 1.3, from
      Arabidopsis thaliana.
AB  - Plastidial degradation of transitory starch yields mainly maltose and glucose.
      Following the export into the cytosol, maltose acts as donor for a glucosyl
      transfer to cytosolic heteroglycans as mediated by a cytosolic transglucosidase
      (DPE2; EC 2.4.1.25) and the second glucosyl residue is liberated as glucose. The
      cytosolic phosphorylase (Pho2/PHS2; EC 2.4.1.1) also interacts with heteroglycans
      using the same intramolecular sites as DPE2. Thus, the two glucosyl transferases
      interconnect the cytosolic pools of glucose and glucose 1-phosphate. Due to the
      complex monosaccharide pattern, other heteroglycan-interacting proteins (HIPs)
      are expected to exist. Identification of those proteins was approached by using
      two types of affinity chromatography. Heteroglycans from leaves of Arabidopsis
      thaliana (Col-0) covalently bound to Sepharose served as ligands that were
      reacted with a complex mixture of buffer-soluble proteins from Arabidopsis
      leaves. Binding proteins were eluted by sodium chloride. For identification, SDS
      PAGE, tryptic digestion and MALDI-TOF analyses were applied. A strongly
      interacting polypeptide (approximately 40kDa; designated as HIP1.3) was observed
      as product of locus At1g09340. Arabidopsis mutants deficient in HIP1.3 were
      reduced in growth and contained heteroglycans displaying an altered
      monosaccharide pattern. Wild type plants express HIP1.3 most strongly in leaves.
      As revealed by immuno fluorescence, HIP1.3 is located in the cytosol of mesophyll
      cells but mostly associated with the cytosolic surface of the chloroplast
      envelope membranes. In an HIP1.3-deficient mutant the immunosignal was
      undetectable. Metabolic profiles from leaves of this mutant and wild type plants
      as well were determined by GC-MS. As compared to the wild type control, more than
      ten metabolites, such as ascorbic acid, fructose, fructose bisphosphate, glucose,
      glycine, were elevated in darkness but decreased in the light. Although the
      biochemical function of HIP1.3 has not yet been elucidated, it is likely to
      possess an important function in the central carbon metabolism of higher plants.

PMID- 21087811
TI  - [Clinical polymorphism of myasthenia gravis beginning with isolated ocular
      symptoms; a five years retrospective analysis].
AB  - INTRODUCTION: myasthenia gravis is a neuromuscular junction disorder that can
      jeopardize the patient's life and has a high clinical polymorphism that makes it
      difficult to diagnose. PATIENTS AND METHODS: after reviewing the disease
      physiology, its clinical symptoms, and the different means to diagnose and treat
      it, we present a 15-patient series that we cared for at the Rothschild
      ophthalmologic foundation from 2002 to 2007 for myasthenia gravis that began with
      isolated ocular symptoms, so as to highlight the clinical diversity of this
      pathology. RESULTS: when the disease was diagnosed, 11 patients out of 15 had a
      ptosis with diplopia, two had an isolated ptosis, and two had isolated diplopia.
      After investigations, we discovered that three patients had a malignant thymoma
      and one had thymic hyperplasia. An autoimmune disease association was found in
      two patients: the first one had Hashimoto thyroiditis and the second one
      developed optical neuromyelitis a few years after his myasthenia gravis. Only
      three patients secondarily developed a generalized myasthenia gravis. DISCUSSION:
      our series of patients has a low disease generalization rate in comparison with
      the published data in the medical literature, indicating that two-thirds of
      patients with ocular myasthenia gravis should develop generalized myasthenia
      gravis within approximately 2 years after the beginning of their illness. This
      could be explained by the early consultation of these patients and the common
      prescription of an immunosuppressive therapy, reducing the risk of secondarily
      generalized myasthenia gravis according to some studies. CONCLUSION: despite the
      small number of patients, this study underlines the clinical polymorphism of
      ocular myasthenia gravis and the risks it may cause. Close collaboration between
      ophthalmologists and neurologists is needed to ensure good care for these
      patients.

PMID- 21087812
TI  - [Double prepapillary arterial loop and arterial occlusion].
AB  - The prepapillary vascular loops are rare congenital vascular anomalies. Often
      unilateral and asymptomatic, they may be complicated by ischemic events by
      twisting or thrombosis of the loop. We report a rare case of double prepapillary
      arterial loop complicated by left retinal ischemia due to thrombosis of the loop.

PMID- 21087813
TI  - [Description of the mental processes occurring during clinical reasoning].
AB  - Clinical reasoning is a highly complex system with multiple inter-dependent
      mental activities. Gaining a better understanding of those cognitive processes
      has two practical implications: for physicians, being able to analyse their own
      reasoning method may prove to be helpful in diagnostic dead end; for medical
      teachers, identifying problem-solving strategies used by medical students may
      foster an appropriate individual feed-back aiming at improving their clinical
      reasoning skills. On the basis of a detailed literature review, the main
      diagnostic strategies and their related pattern of mental processes are described
      and illustrated with a concrete example, going from the patient's complaint to
      the chosen solution. Inductive, abductive and deductive diagnostic approaches are
      detailed. Different strategies for collecting data (exhaustive or oriented) and
      for problem-building are described. The place of problem solving strategies such
      as pattern-recognition, scheme inductive process, using of clinical script,
      syndrome grouping and mental hypotheses test is considered. This work aims at
      breaking up mental activities in process within clinical reasoning reminding that
      expert reasoning is characterised by the ability to use and structure the whole
      of these activities in a coherent system, using combined strategies in order to
      guarantee a better accuracy of their diagnosis.

PMID- 21087814
TI  - Kidney transplant patients' perceptions, beliefs, and barriers related to regular
      nephrology outpatient visits.
AB  - BACKGROUND: Our previous work has shown substantial national variation in the
      frequency of nephrology visits after kidney transplant. The low frequency of
      nephrology visits was associated with increased risk of transplant failure.
      METHODS: We performed a qualitative study that included interviews and 5 focus
      groups of transplant recipients. The study took place at a transplant center in
      the Upper Midwest. Participants (N = 39) were selected if they had at least one
      of the previously described risk factors for decreased nephrology visits: ethnic
      minority, lower median household income, and residence less than 10 miles from
      the transplant center. The goal was to assess patients' perceptions and beliefs
      and perceived barriers to regular nephrology outpatient visits. All transcripts
      were coded using software for qualitative data analysis. RESULTS: Transplant
      recipients understood the importance of keeping nephrology appointments and
      reflected positively on them. Regardless, they perceived barriers to adhering to
      the visit schedule, such as a value on self-reliance, which they described as
      increasing over time since transplant; a growing sense that they could interpret
      their bodies independently without needing to see the physician as regularly; and
      finally, the multitude of physical and mental health challenges inherent to
      posttransplant life. Other factors motivated patients to keep their regular
      nephrology visits, such as peer-support relationships and talking to other
      patients on dialysis therapy. Patients reported that talking to patients who had
      received a transplant before them helped them anticipate and cope with the mental
      and physical challenges associated with life posttransplant. A study limitation
      was that all participants were from a single transplant center. CONCLUSIONS:
      Although kidney transplant recipients understood the importance of keeping
      nephrology appointments, there were significant perceived barriers to these
      visits. Future interventions should address perceived barriers and motivate
      patients to keep regular nephrology visits posttransplant as a way to improve
      transplant outcomes.

PMID- 21087815
TI  - Filling the gap in CKD: The health care workforce and faculty development.
AB  - Given limited resources, adding another chronic illness to the panoply of chronic
      disease care is problematic. Nevertheless, chronic kidney disease (CKD) is
      increasing in recognition and prevalence across the world, and a management
      strategy for this growing population is necessary. A diverse group of health care
      professionals interacts with patients with CKD and their family members,
      including nurses, nurse practitioners, dieticians, social workers, pharmacists,
      physicians, physical therapists, physician assistants, and public health workers.
      All these individuals have the opportunity to reinforce CKD management. This
      potentially would bring a broader health care workforce to bear on CKD, reducing
      the impact of the nephrology workforce shortage. To realize such a strategy, it
      is necessary to bolster CKD awareness and knowledge in the diverse health care
      workforce. A faculty development program that extends CKD awareness to existing
      health care workers also has the possibility of migrating into the learner
      curriculum in health professional schools. This approach would expand CKD
      education, creating a skilled diverse health care workforce.

PMID- 21087816
TI  - A case of phospholipase A2 receptor-positive membranous nephropathy preceding
      sarcoid-associated granulomatous tubulointerstitial nephritis.
AB  - We report the case of a 29-year-old man with membranous nephropathy that was
      associated with a sarcoidosic granulomatous tubulointerstitial nephritis, but was
      without an apparent calcium metabolism disorder. Corticosteroid treatment was
      associated with remission of nephrotic syndrome. We discuss the relationship
      between membranous nephropathy and sarcoidosis based on the close appearance of
      the 2 diseases and the detection of phospholipase A2 receptor in glomerular
      immune deposits.

PMID- 21087817
TI  - CKD awareness and blood pressure control in the primary care hypertensive
      population.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with poor renal and
      cardiovascular outcomes, and early identification largely depends on general
      practitioners' (GPs') awareness of it. To date, no study has evaluated CKD
      prevalence in patients with hypertension in primary care. STUDY DESIGN: Cross
      sectional evaluation of the Italian GPs' database. SETTING & PARTICIPANTS: 39,525
      patients with hypertension representative of the Italian hypertensive population
      followed up by GPs in 2005. FACTOR: Estimated glomerular filtration rate (eGFR);
      eGFR <60 mL/min/1.73 m2 was defined as CKD. OUTCOMES: GPs' awareness of CKD
      assessed using International Classification of Diseases, Ninth Revision, Clinical
      Modification diagnostic codes for CKD, and blood pressure (BP) control.
      MEASUREMENTS: Data concerning serum creatinine levels, BPs, and antihypertensive
      medications were obtained for each patient from the GPs' database; eGFR was
      calculated according to the 4-variable Modification of Diet in Renal Disease
      (MDRD) Study equation. RESULTS: CKD prevalence was 23%, but kidney disease was
      diagnosed by GPs in only 3.9% of patients. BP control was inadequate in patients
      with CKD and those with eGFR >60 mL/min/1.73 m2, with only 44% of patients
      reaching a BP target <140/90 mm Hg and 11% achieving <130/80 mm Hg. Patients with
      eGFR <60 mL/min/1.73 m2 whose GPs were aware of CKD were more likely to reach
      recommended BP target values (OR, 1.35; 95% CI, 1.15-1.59; P < 0.001).
      LIMITATIONS: The prevalence of decreased eGFR may be overestimated because of the
      lack of creatinine calibration. Proteinuria data were not available. CONCLUSIONS:
      Awareness of CKD by GPs is critical for achieving the recommended guideline BP
      targets. However, awareness of CKD by GPs is still far too low, highlighting the
      need to systematically adopt eGFR for more accurate identification of CKD in high
      risk populations.

PMID- 21087818
TI  - DNA methylation in thoracic neoplasms.
AB  - Thoracic neoplasms, which include lung cancers, esophageal carcinoma, and thymic
      epithelial tumors, are the leading causes of tumor-related death and a major
      health concern worldwide. The development of neoplasms is a multistep process
      involving both genetic and epigenetic alterations. A growing body of research
      provides evidence that aberrant DNA methylation, including DNA hypermethylation
      in promoter regions, global DNA hypomethylation and the overexpression of DNA
      methyltransferases, plays an important role in tumorigenesis. In this review, we
      summarize published observations of methylation pattern disruptions in thoracic
      tumors, and discuss how these abnormalities contribute to the development of
      cancers. We review recent findings showing that suppressing the activity of the
      DNA methylating enzymes DNMTs can have potent anti-cancer effects, and discuss
      the possibility of developing novel therapies for thoracic tumors based on DNMT
      inhibition.

PMID- 21087819
TI  - Iminodiacetic acid functionalized cation exchange resin for adsorptive removal of
      Cr(VI), Cd(II), Ni(II) and Pb(II) from their aqueous solutions.
AB  - Iminodiacetic acid functionality has been introduced on styrene-divinyl benzene
      co-polymeric beads and characterized by FT-IR in order to develop weak acid based
      cation exchange resin. This resin was evaluated for the removal of different
      heavy metal ions namely Cd(II), Cr(VI), Ni(II) and Pb(II) from their aqueous
      solutions. The results showed greater affinity of resin towards Cr(VI) for which
      99.7% removal achieved in optimal conditions following the order
      Ni(II)>Pb(II)>Cd(II) with 65%, 59% and 28% removal. Experiments were also
      directed towards kinetic studies of adsorption and found to follow first order
      reversible kinetic model with the overall rate constants 0.3250, 0.2393, 0.4290
      and 0.2968 for Cr(VI), Ni(II), Pb(II) and Cd(II) removal respectively. Detailed
      studies of Cr(VI) removal has been carried out to see the effect of pH, resin
      dose and metal ion concentration on adsorption and concluded that complexation
      enhanced the chromium removal efficacy of resin drastically, which is strongly pH
      dependent. The findings were also supported by the comparison of FT-IR spectra of
      neat resin with the chromium-adsorbed resin.

PMID- 21087820
TI  - Removal of cephalexin from aqueous solutions by original and Cu(II)/Fe(III)
      impregnated activated carbons developed from lotus stalks Kinetics and
      equilibrium studies.
AB  - Lotus stalk activated carbon (AC) was produced by ultrasound digestion of lotus
      stalks in H(3)PO(4). Copper nitrate and iron nitrate were used to impregnate AC,
      producing Cu(II)-impregnated AC (AC-Cu) and Fe(III)-impregnated AC (AC-Fe). The
      modified ACs were characterized by N(2) adsorption-desorption isotherms, Fourier
      transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The
      adsorption kinetics and isotherms of cephalexin (CEX) in aqueous solution were
      studied for AC, AC-Cu and AC-Fe. The kinetics and equilibrium data agreed well
      with the pseudo-second-order kinetics model and Freundlich isotherm model for all
      three adsorbents. The results also showed that the adsorption capacities of AC-Cu
      and AC-Fe were larger than the capacity of AC and AC-Fe was found to be the most
      effective at the removal of CEX in solution. Furthermore, batch experiments were
      conducted to study the effects of pH (2.5-10.5), initial concentration of CEX (4
      16 mg/L), ionic strength (10-1000 mM) on CEX removal.

PMID- 21087821
TI  - Simultaneous exposure of non-diabetics to high levels of dioxins and mercury
      increases their risk of insulin resistance.
AB  - Insulin resistance and the defective function of pancreatic beta-cells can occur
      several years before the development of type 2 diabetes. It is necessary to
      investigate and clarify the integrated effects of moderate-to-high exposure to
      dioxins and mercury on the pancreatic endocrine function. This cross-sectional
      study investigated 1449 non-diabetic residents near a deserted pentachlorophenol
      and chloralkali factory. Metabolic syndrome related factors were measured to
      examine associations with serum dioxin and blood mercury. We also investigated
      associations between insulin resistance (HOMA-IR > 75th percentile), defective
      pancreatic beta-cells function (HOMA beta-cell > 75th percentile), serum dioxins
      and blood mercury. After adjusting for confounding factors, we found that insulin
      resistance increased with serum dioxins (b = 0.13, P < 0.001) and blood mercury
      (b = 0.01, P < 0.001). Moreover, participants with higher serum dioxins or blood
      mercury were at a significantly increasing risk for insulin resistance (P(trend)
      < 0.001). The joint highest tertile of serum dioxins and blood mercury was
      associated with elevated HOMA-IR at 11 times the odds of the joint lowest tertile
      (AOR 11.00, 95% CI: 4.87, 26.63). We hypothesize that simultaneous exposure to
      dioxins and mercury heightens the risk of insulin resistance more than does
      individual exposure.

PMID- 21087822
TI  - The fate and transport of RDX, HMX, TNT and DNT in the volcanic soils of Hawaii:
      a laboratory and modeling study.
AB  - The adsorption and degradation behavior of RDX, HMX, TNT and DNT and the impact
      of pH, ionic strength and dissolved organic matter on sorption were examined for
      two volcanic soils of a former military training area on Hawaii Island, Hawaii,
      USA. The transport of these chemicals in the soil was also studied in small
      packed columns and simulated using a water-flow and solute-transport model,
      HYDRUS_1D. The results show that HMX and RDX are both significantly more mobile
      than TNT and DNT. The adsorbability of the four chemicals was ranked as:
      RDX<HMX<TNT<DNT and their half-lives were ranked as: HMX>RDX>DNT>TNT. No
      significant trend was observed for the effect of ionic strength, pH and dissolved
      organic carbon (DOC) on the adsorption of explosive compounds within the
      concentrations and pH ranges evaluated. The simulation results show that TNT and
      DNT would not leach beyond a depth of 30cm soil profile whereas a significant
      amount of HMX and RDX would pass the 30cm depth. It seems that the risk for
      contamination of groundwater is much higher for both HMX and RDX than for DNT and
      TNT as the substratum in this area consists of highly permeable lavas.

PMID- 21087823
TI  - Moving differently in pain: a new theory to explain the adaptation to pain.

PMID- 21087824
TI  - From descending pain modulation to obesity via the medullary raphe.

PMID- 21087825
TI  - Intravenous arginine and human skin graft donor site healing: a randomized
      controlled trial.
AB  - BACKGROUND AND AIMS: Studies evaluating the effect of arginine supplementation in
      human wound healing are inhomogeneous with conflicting results. This study aims
      to clarify the role of arginine supplementation in the healing of human skin
      graft donor sites. METHODS: 35 subjects undergoing skin autografting were
      randomly assigned to receive intravenous arginine (n = 16) or placebo (n = 19)
      for 5 days in a dose of 30 g of arginine or an isovolumetric amount of placebo
      (25.2g of alanine). Wound healing was evaluated at the donor sites by
      objectifying angiogenesis, reepithelialization and neutrophil influx. Plasma
      amino acid concentrations were measured to evaluate our intervention. RESULTS:
      The two groups were comparable in age, morbidity and nutritional, metabolic and
      inflammatory state. Plasma arginine and alanine levels increased significantly
      upon supplementation in the two groups, respectively. No differences were found
      between the arginine supplementation group and the placebo group in the studied
      parameters. Placebo vs. arginine; mean +/- SD: neutrophil influx on day 2: 6.67
      +/- 3.0 vs. 6.57 +/- 3.3, p = 0.66; angiogenesis on day 10: 8.0 +/- 2.8 vs. 8.9
      +/- 3.1; reepithelialization in % on day 10: 81 +/- 8.5 vs. 85 +/- 7.1.
      CONCLUSION: Intravenous arginine supplementation does not improve angiogenesis,
      reepithelialization or neutrophil influx in healing of human skin graft donor
      sites.

PMID- 21087826
TI  - Evaluation of infrastructure, equipment and training of 28 burn units/burn
      centers in Germany, Austria and Switzerland.
AB  - Treatment of burn patients requires special training and skills, and an adequate
      infrastructure. In the United States, burn center referral criteria and
      requirements of burn centers are defined by the American Burn Association (ABA)
      in the Guidelines for the Operation of Burn Centers, and in Germany, by the
      German Society for Burn Treatment (DGV). The European Burn centers in Austria and
      the German-speaking part of Switzerland share the standards in the setting of the
      German-speaking Association for Burn Therapy (DAV) with some modifications. The
      aim of this study was to evaluate the current infrastructure of burn centers in
      the three German-speaking countries with respect to the existing guidelines.
      Therefore, guidelines for burn center referral criteria and burn center
      requirements were compared between the USA (ABA) and Germany (DGV). In addition,
      a questionnaire was sent to all burn centers in Germany, Austria and the German
      speaking part of Switzerland, in order to collect current information regarding
      the architectural and medical infrastructure, available equipment and care
      providing personnel. The comparison of guidelines for the USA and Germany
      revealed similar burn center referral criteria for both countries. With respect
      to burn center requirements, both the USA and Germany have similar requirements,
      albeit with different focus points. In Germany, the main focus lies on the
      infrastructural requirements for burn centers, while in the US, the main focus
      lies on the requirements for medical and nursing personnel. Critical review of
      the responses from the burn centers of German-speaking countries revealed that
      the biggest infrastructural differences among centers were observed in burn units
      providing pediatric care, as compared to adult burn centers. In summary, the DGV
      guidelines for German-speaking countries reflect an overall adoption of the ABA
      guidelines, and the burn centers included in this study met those requirements.
      As a result of the positive experience and effective treatment of burn patients
      in German-speaking countries, we recommend an adoption of the ABA guidelines to
      those countries and societies that are in need of appropriate standards of burn
      care.

PMID- 21087827
TI  - Another possible cell source for cardiac regenerative medicine: reprogramming
      adult fibroblasts to cardiomyocytes and endothelial progenitor cells.
AB  - Ischemic heart disease (IHD) is a significant burden to healthcare systems in the
      world despite substantial advances in risk modification, pharmacological therapy
      and revascularization therapy. Stem cell therapy is emerging as a novel
      therapeutic paradigm for myocardial repair. Several cell types including
      embryonic stem cells, adult stem cells and induced pluripotent stem (iPS) cells
      have been used for the treatment of ischemic heart disease. But all these
      engrafted cells must be systematically or locally administered after being
      expanded in vitro, the rare differentiation into cardiomyocytes and low cellular
      survival of engrafted cells also limited the efficacy of stem cell therapy.
      Recent research indicated that it was feasible to reprogramme one mature cell
      type into another cell type directly by introducing several transcription
      factors, which was called transdifferentiation. We speculate that cell
      reprogramming might provide potential new cell sources for therapeutic cardiac
      regeneration. For these reasons, we hypothesize that converting cardiac
      fibroblasts to cardiomyocytes and endothelial progenitor cells (EPCs) either in
      vivo or in vitro might be a possible way for future therapeutic cardiac
      regeneration. Furthermore we also analyzed the possible difficulties we might
      face on way to realize this hypothesis.

PMID- 21087828
TI  - Anorexia nervosa and the insula.
AB  - Anorexia nervosa is a serious illness with major physical and psychological
      morbidity. It has largely been understood in terms of cultural and environmental
      explanations. However these are insufficient to explain the diverse clinical
      features of the illness, nor its rarity given the universality of sociocultural
      factors. Over the last 20 years, there has been a steady accumulation of
      neurobiological evidence requiring a re-formulation of current causal models. We
      now offer a new empirically-derived hypothesis implicating underlying rate
      limiting dysfunction of insula cortex as a crucial risk factor for the
      development of anorexia nervosa. Supporting evidence for this hypothesis is drawn
      from anatomical and clinical research of insula cortex damage in humans and
      neuroscientific studies of relevant clinical features including taste, pain
      perception and reward processing. This hypothesis, if sustainable, would be the
      first fully to explain the disorder and predicts promising novel treatment
      possibilities including Cognitive Remediation and Motivation Enhancement
      Therapies. The knowledge that the challenging behaviours, so characteristic of
      AN, are the result of underlying cerebral dysfunction, rather than being purely
      volitional, could help to reduce the stigma patients experience and improve the
      therapeutic alliance in this poorly understood and difficult to treat disorder.

PMID- 21087829
TI  - Upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1
      promotes the progression of human gliomas.
AB  - Matrix metalloproteinases (MMPs) have been proposed to be involved in remodeling
      the tumor-stromal microenvironment. The protease-activated receptors (PARs) are
      the latest MMP targets. Recent studies have revealed that stromal-derived MMP-1
      acts as a signaling molecule by cleaving PAR1 to cause tumor migration and
      invasion of various cancers. However, the involvement of MMP-1/PAR1 signaling
      pathway in the progression and prognosis of human gliomas remains to be
      identified. Immunohistochemical staining was performed to detect the expression
      patterns of MMP-1 and PAR1 in biopsies from 108 patients with primary gliomas.
      Kaplan-Meier survival and Cox regression analyzes were performed to evaluate the
      prognosis of patients. Immunostaining revealed MMP-1 to be expressed in 83.3%
      (90/108) and PAR1 in 76.9% (83/108) of the biopsies. PAR1 expression was
      significantly correlated with that of MMP-1 (r = 0.786, p<0.0001). The total IHC
      scores for MMP-1 and PAR1 were significantly higher in high-grade tumors than in
      low-grade tumors (both p = 0.001). In addition, patients with high MMP-1 and high
      PAR1 expression have lower Karnofsky performance scale (KPS) scores than patients
      with low MMP-1 and low PAR1 expression (both p = 0.008). Moreover, MMP-1 and PAR1
      expression was shown to be a strong prognostic marker for decreased overall
      survival (p = 0.002 and 0.003, respectively). Furthermore, Cox multi-factor
      analysis showed that KPS (p = 0.008), WHO grade (p = 0.006), MMP-1 (p = 0.006),
      and PAR1 (p = 0.008) were independent prognostic factors for human gliomas. Our
      results suggest that in gliomas, the upregulation of MMP-1 and PAR1 correlates
      with histological malignancy grade and clinical outcome. Also, MMP-1 and PAR1
      immunostaining supplements the current histological grading by offering
      additional prognostic and predictive information.

PMID- 21087830
TI  - Colorimetric detection of urea nitrate: the missing link.
AB  - Traces of the improvised explosive urea nitrate can be characterized by a
      sensitive colorimetric reaction with p-dimethylaminocinnamalaldehyde (p-DMAC, UN
      1 reagent). As recently shown, the dark red product has a structure of a
      protonated Schiff base. The unprotonated free base, previously postulated in the
      literature to be the colored product, was now prepared and fully characterized.
      It shows totally different spectroscopic properties from the dark red compound.
      Similarly, the analogous free base of the reaction between urea nitrate and the
      one-vinyl shorter reagent, p-dimethylaminobenzaldehyde, was synthesized and
      characterized. Similar differences between the free and protonated forms were
      observed. The protonated Schiff base spontaneously decomposes to the free base
      over time. This study provides the missing link in the elucidation of the
      colorimetric reaction between urea nitrate and UN-1. Both colored products show
      characteristics of typical acid-base indicators.

PMID- 21087831
TI  - [Mitral valve endocarditis complicated by septic pulmonary emboli].

PMID- 21087832
TI  - [Assessment of adherence to Afssaps guidelines for the prescription of
      antifungals in pediatric hemato-oncology].
AB  - OBJECTIVE: This study had for aim to identify factors limiting the implementation
      of clinical guidelines related to the use of expensive antifungal drugs in
      pediatric hemato-oncology. DESIGN: A retrospective study was conducted in a Lyon
      teaching hospital (France), from February to December 2008. The compliance of
      antifungal prescription to French guidelines was assessed. Audit findings were
      interpreted using both semi-directed interviews of six prescribers (qualitative
      approach) and statistical analysis of prescriptions (quantitative approach).
      RESULTS: Fifty antifungal prescriptions were studied. The compliance with
      clinical guidelines reached 66% (CI 95% 52-80%). The semi-directed interviews
      revealed that five issues may have influenced the adherence of prescribers with
      recommended practices: the guidelines, the molecule, the prescriber, the child,
      and practice settings. The statistical analysis did not reveal any link between
      the prescriber's activities or his department and the compliance with guidelines.
      A significant association was found between the documentation of infection and
      the non-conformity of antifungal prescriptions (p=0.02). CONCLUSIONS: This study,
      combining qualitative and quantitative assessments, addressed potential issues
      related to the implementation of guidelines in specific patient groups or to
      their adaptation in the context of pediatric hematology-oncology. Harmonization
      of practices related to the widespread use of antifungal associations is
      required.

PMID- 21087833
TI  - Local infections after oral sex.

PMID- 21087834
TI  - Herpes zoster in a 13-year-old healthy immunocompetent female patient.

PMID- 21087835
TI  - Radiological and clinical outcome after operations in patients with congenital
      deficiencies of the wrist and hand.
AB  - PURPOSE: To evaluate the incidence, therapy results, complications and radiologic
      workup of operatively treated congenital disorders of the hand and wrist in a
      large university center during a 10-year period. METHODS: The institutional
      database was retrospectively analysed for patients with congenital disorders of
      the hand and wrist treated operatively during a 10-year period (1998-2007).
      Disorders were classified according to Van Schoonhoven into 11 different
      entities. For each entity the incidence, the patients' age at the time of
      operation, the pre- and postoperative clinical and radiological workup and the
      frequency of complications and reoperations were evaluated. RESULTS: A total of
      278 patients was treated operatively for congenital disorders of the hand and
      wrist with syndactyly being present in 112, thumb hypoplasia in 15, polydactyly
      in 11, radial clubhand in 7, radioulnar synostosis in 6, clinodactyly in 6, thumb
      duplication in 6, brachydactyly in 4 and macrodactyly in 4 cases. Patients' age
      at the time of operation varied substantially between the different entities with
      a mean age between 0.9 and 6.2 years. There were 9 complications (3%, n = 278)-
      all of them infections. There were 28 reoperations (10%, n = 278), 13 of them
      (5%, n = 278) due to reoccurring webs in syndactyly. CONCLUSION: Congenital
      disorders of the hand and wrist include various rare diseases with syndactyly and
      thumb hypoplasia being the most frequent entities. As a rule, diagnosis is
      obtained clinically. Radiologic workup typically consists of plain radiography.
      Complications are rare, whereas reoperations are frequent, mostly due to
      reoccurring webs in syndactyly.

PMID- 21087836
TI  - In-line reaction monitoring of entacapone synthesis by Raman spectroscopy and
      multivariate analysis.
AB  - In-line Raman spectroscopy and multivariate analysis were used to monitor
      Knoevenagel condensation reaction, the final step in preparation of drug
      entacapone. By applying a fiber optical Raman probe immersed into a reaction
      vessel Raman spectra of the reaction mixture were recorded in situ during the
      entacapone synthesis in toluene, heptane and isobutyl acetate. Due to the
      complexity of the measured spectra, the obtained data were analyzed and
      interpreted by means of principal component analysis. It has been shown that
      progress of this reaction can be monitored in real-time and reaction end points
      can be determined in different solvents. The reaction was found to be the fastest
      in heptane due to the lower loss of the catalyst. For a comparison the reaction
      was independently monitored by off-line Raman spectroscopy and liquid
      chromatography which confirmed the results obtained in-line. The results
      presented here have shown that this in-line approach can be used as a fast, non
      destructive and reliable method to monitor the Knoevenagel reaction in real time.
      The knowledge gained in this study can further be exploited for the industrial
      process control.

PMID- 21087837
TI  - The quality of mental disorder information websites: a review.
AB  - OBJECTIVE: This paper reviews studies assessing the quality of websites providing
      information about mental disorders. METHODS: The review included 31 articles
      identified by searching research databases in March 2010. Topics covered included
      affective disorders, anxiety disorders, eating disorders, substance use disorders
      and schizophrenia/psychosis. RESULTS: The largest number of articles (13)
      reported studies assessing affective disorder information quality. Methodologies
      varied in site selection and rating methods, with some of limited validity. Most
      concluded that quality was poor, although quality of affective disorder sites may
      be improving. CONCLUSION: There is currently very little understanding of the
      influence of website quality on user behaviour. Future quality assessments might
      use the criteria informed by key behaviour change theories. PRACTICE
      IMPLICATIONS: A possible approach to research on websites and user behaviour
      might be to develop an evaluation framework incorporating strategies from
      behaviour change models, key mental health literacy elements and health outcomes
      relevant to mental health promotion.

PMID- 21087838
TI  - Adolescent mothers' perspectives regarding their own psychosocial and health
      needs: a qualitative exploratory study in Belgium.
AB  - OBJECTIVES: We looked at early pregnancy and parenthood as an opportunity to
      broaden our understanding of the reproductive health education needs met by
      adolescent girls. METHODS: We conducted an in-depth interview study with 12
      adolescent mothers. RESULTS: To become a mother at a young age was perceived as
      meaningful to all the participants. The participants expressed a need to be
      addressed as adult parents, who want the best for their child. A variety of
      psychosocial and health needs emerged over a time span ranging from starting to
      be sexually active to after the child was born. Social isolation was found to be
      an important factor of vulnerability. CONCLUSION: The health needs of adolescent
      mothers extend well beyond counselling around the decision to continue or
      terminate pregnancy, and subsequent information on contraception methods to avoid
      further pregnancies. Adolescent mothers need to be supported in their transition
      to parenthood, and special care should be provided to girls who are socially
      isolated. PRACTICE IMPLICATIONS: We identified several avenues for health
      education and counselling to adolescent mothers, from primary prevention to
      reduce incidence of early pregnancies to tertiary prevention to reduce negative
      health outcomes for both mother and child.

PMID- 21087839
TI  - [Lymphatic system: Anatomy, histology and physiology].
AB  - Our knowledge of the anatomy of the lymphatic system may have changed little, if
      at all, since the first descriptions of this system in the 17th and 18th
      centuries, but the identification of specific markers of lymphatic endothelial
      cells and of some of the genes involved in the occurrence of lymphoedema in
      humans has revolutionized our understanding. This article provides an overview of
      current fundamental knowledge relating to lymphoedema based on both the
      historical anatomy description and the most recent data about lymphangiogenesis.

PMID- 21087840
TI  - Differential hyaluronan homeostasis and expression of proteoglycans in juvenile
      and adult human skin.

PMID- 21087841
TI  - Self-assembled micelles of novel graft amphiphilic copolymers for drug controlled
      release.
AB  - In this study, with the aim of designing an ideal anticancer drug carrier, we
      synthesized novel amphiphilic graft copolymers, P(Glu-alt-PEG)-graft-PCLA, based
      on poly(ethylene glycol) (PEG) segments and glutamic acid (Glu) units as the
      hydrophilic main chain, and poly(E-caprolactone-co-lactide) (PCLA) as hydrophobic
      branches. The chemical structure of the copolymers was characterized by (1)H MNR
      and FT-IR. The self-assembly of the copolymers to form micelles was studied by
      TEM, DLS and fluorescence spectroscopy. In vitro doxorubicin controlled release
      studies demonstrated that these graft copolymer micelles had high drug loading
      capacity and good controlled released properties, demonstrating their potential
      as a novel anticancer drug carrier. The drug loaded graft copolymer micelles
      exhibited efficient inhibition of HeLa cells in in vitro studies.

PMID- 21087842
TI  - Controllable biodegradability, drug release behavior and hemocompatibility of PTX
      eluting magnesium stents.
AB  - Cardiovascular magnesium-based stents have been already applied in patients.
      However, their high corrosion rate hinders their clinical application. In this
      study, we adopt a new approach in the design of a Mg-based stent to improve the
      biodegradation rate and the drug release rate. By fabricating a micro-arc
      oxidation/poly-l-lactic acid (MAO/PLLA) composite coating on the magnesium alloy
      AZ81 substrate, the corrosion resistance decreased and the biodegradation rate
      became controllable. The drug release coating was composed of one Poly(dl-lactide
      co-glycolide)/paclitaxel (PLGA/PTX) layer and one pure PLGA blank layer without
      paclitaxel, and this coating also functions to provide controlled biodegradation
      rate of the stent. The drug release rate was controlled by controlling the ratio
      of the LA:GA of the PLGA without PTX. The scanning electron microscopy (SEM)
      images were used to demonstrate the morphology of the samples before and after
      this modification. The blood compatibility of the samples was demonstrated by the
      platelet adhesion test. The drug release was determined by ultraviolet-visible
      (UV-visible) spectrophotometer. The result showed that the PLLA effectively
      sealed the micro-cracks and micro-holes on the surface of the MAO coating to give
      controllable biodegradation of the AZ81. The drug release rate of PTX exhibited a
      nearly linear sustained-release profile with no significant burst releases that
      would come from the uncontrolled oxidation/corrosion of AZ81. The samples
      modified had better hemocompatibility than 316L stainless steel.

PMID- 21087843
TI  - Biosynthesis of silver, gold and bimetallic nanoparticles using the filamentous
      fungus Neurospora crassa.
AB  - The development of production processes that can reduce the environmental impact,
      offer waste reduction and increase energy efficiency is an important step in the
      field of application of nanotechnology. In this work the filamentous fungus
      Neurospora crassa was screened and found to be successful for the production of
      mono and bimetallic Au/Ag nanoparticles (NPs). Analysis by scanning electron
      microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and transmission
      electron microscopy (TEM) confirmed the biosynthesis of NPs by the fungus. The
      shape of NPs was found to be mainly spherical with average diameter of 11nm for
      silver and 32nm for gold, when the fungus was exposed to the aqueous solutions of
      10(-3)M of AgNO(3) and HAuCl(4), respectively. EDS analysis also confirmed the
      formation of alloy-type Au/Ag bimetallic NPs when three different ratios of
      AgNO(3)/HAuCl(4) were used. TEM images of thin sections of N. crassa cells
      confirmed the intracellular formation of silver and gold NPs. The results
      obtained indicate that N. crassa can be a potential "nanofactory" for the
      synthesis of metallic NPs. The use of this organism will offer several advantages
      since it is considered as a non-pathogenic organism, has a fast growth rate,
      rapid capacity of metallic ions reduction, NPs stabilization and facile and
      economical biomass handling.

PMID- 21087844
TI  - [Recurrent flaccid paralysis indicative of acute intermittent porphyria in a
      child].
AB  - Porphyrias are inherited metabolic diseases characterized by accumulation and
      increased excretion of porphyrins due to enzyme deficiencies involved in the
      biosynthesis of heme. Porphyrias are monogenic autosomal and mostly dominant
      disorders. CASE REPORT: A 10-year-old boy was diagnosed with acute intermittent
      porphyria on the basis of recurrent flaccid paralysis with red urine.
      Confirmation was obtained by measurement of urinary porphyrin precursors and
      chromatography of porphyrins. CONCLUSION: Acute intermittent porphyria is a
      severe form of hereditary porphyria with severe neurological complications during
      an acute episode. Specific investigations should be performed early and urgently
      in the presence of suggestive signs in a child.

PMID- 21087845
TI  - [Benign but not harmless intracranial hypertension: a case report].
AB  - Benign intracranial hypertension (BIH) is characterized as an intracranial
      pressure increase occurring in the absence of brain tumour, sinus thrombosis or
      hydrocephaly. But contrary to what its designation might suggest, it threatens
      the visual prognosis. We report the case of a 15-year-old girl with lymphocytic
      meningitis, developing secondary a BIH. Cerebrospinal fluid pressure was 70cm
      water, without enlargement of the cerebral ventricles. Along with the
      progression, bilateral 6th nerve palsy, impairment of visual acuity and bilateral
      papilledema appeared. No cause was found after a complete assessment. Treatment
      consisted in oral acetazolamide and 9 depletive spinal taps. Clinical
      examination, fundus examination and Goldmann visual field normalized after 8
      weeks. No relapse occurred after a 1-year follow-up. This case shows that BIH,
      which is not a well-known disorder, is incorrectly referred to as benign: both
      prompt diagnosis and proper management are of major importance.

PMID- 21087846
TI  - [Neonatal screening for sickle cell disease at the Nice University Hospital: the
      last 8 years].
AB  - INTRODUCTION: Screening for sickle cell disease, the most common of recessive
      autosomic hemoglobin disorders, allows detection of sickle cell disease SCD
      (homozygous sickle cell disease, compound heterozygote SC, and S beta
      thalassemia) in a target population. Our objective was to evaluate its
      effectiveness at the Nice University Hospital. POPULATION AND METHODS: This
      prospective study was conducted between 1 January 2000 and 31 December 2008. The
      national targeted newborn screening, run together with the Guthrie test on the
      3rd day of life, offered at-risk newborns (based on ethnicity and family
      history), allow the detection of qualitative hemoglobin abnormalities. A
      confirmatory test is performed when positive. Gender, ethnicity, type of
      hemoglobin found, zygosity, age at diagnosis, the presence at a 2nd consultation
      of the families identified, and acceptance of the confirmatory test were
      collected and analyzed. RESULTS: A total of 19,775 children were born in Nice
      University Hospital during this period, among whom screening detected 151
      hemoglobinopathies: 139 heterozygotes and 12 major sickle cell syndrome (9 SS and
      3 S beta-thalassemia). The prevalence of SCD on the targeted and the total
      population was, respectively, 1 out of 659 and 1 out of 1648 and the prevalence
      of heterozygotes was 1 out of 57 and 1 out of 142. The sex ratio was close to 1.
      Hemoglobin S predominated (74% of pathogens Hb). The Maghreb and sub-Saharan
      Africa were the 2 main areas of origin. One hundred and four of 151 families,
      including 12 cases of SCD, returned to consultation after they received a letter
      requesting attendance at a 2nd consultation. For 80 children, the confirmatory
      test was accepted. Feedback was possible for 72 of the 80 families. DISCUSSION:
      The number of children screened is increasing, thanks to better awareness among
      medical staff. The prevalence of SCD and heterozygotes found in Nice University
      Hospital is similar to what is described in the literature. With screening, early
      diagnosis allows early treatment at the age of 2 months before the occurrence of
      complications, reducing morbidity and mortality. CONCLUSION: Screening for sickle
      cell disease appears effective in Nice. It seems necessary to continue focusing
      on the importance of screening among maternity healthcare actors.

PMID- 21087847
TI  - Regulation of immunity and autoimmunity by B cells.
AB  - Compelling evidence has demonstrated that IL-10-producing regulatory B cells
      (B(regs)) are specialized to suppress immune responses and control various
      immunopathologies. Several reports have provided information on the phenotype,
      generation, and mechanism of action of B(regs). Recent work has also identified
      B(regs) in humans and has begun to unravel their phenotype and mode of
      suppression. A complete analysis of their function in immune-mediated diseases is
      required for possible future use of B(regs) as a part of new clinical strategies
      for treating autoimmune diseases and in the induction of transplant tolerance.

PMID- 21087848
TI  - IL-17 and IL-22 in atopic allergic disease.
AB  - A long standing paradigm is that antigen-specific Th2 cells and their cytokines
      such as IL-4, IL-5, and IL-13 orchestrate the characteristic features of atopic
      allergy. The discovery of a role for IL-17-producing (Th17) and IL-22-producing
      (Th22) T helper cells in inflammatory diseases has added an additional layer of
      complexity to the understanding of the pathogenesis of allergic diseases. Here we
      re-evaluate the role of T helper cells, with special focus on the Th17 and Th22
      subsets in allergic asthma and atopic dermatitis. Whereas sparse data point to a
      protective role of the increasing amounts of Th22 cells that are found in chronic
      stages of both allergies, the data on Th17 cells paint different pictures for the
      contribution of Th17 cells during subsequent stages of these two forms of
      allergy.

PMID- 21087850
TI  - Workers' exposure to dust, endotoxin and beta-(1-3) glucan at four large-scale
      composting facilities.
AB  - OBJECTIVES: To characterise compost workers' exposure to dust, endotoxin and beta
      (1-3) glucan during various operational practices and investigate whether dust
      concentrations are a useful indicator of endotoxin exposure in compost workers.
      METHODS: This study assessed inhalable dust fractions, bacterial endotoxin and
      beta-(1-3) glucan in 117 personal samples and 88 ambient samples from four large
      scale composting facilities. RESULTS: Employees' exposures to inhalable dust,
      endotoxin and beta-(1-3) glucan exhibited a large range. Inhalable dust was found
      to be generally low (GM 0.99 mg/m(3), GSD 2.99 mg/m(3)). Analysis of the
      biological component of the dust showed that employees' exposures to endotoxin
      were elevated (GM 35.10 EU/m(3), GSD 9.97 EU/m(3)). Employees' exposure to beta
      (1-3) glucan was low (GM 0.98 ng/m(3), GSD 13.39 ng/m(3)). Dust levels were
      elevated during manual sorting and screening of waste and high levels of
      endotoxin and beta-(1-3) glucan were observed during all practices involving the
      movement of waste. A significant correlation was observed between the personal
      dust levels and personal endotoxin concentrations (r=0.783, p<0.05) and that
      personal inhalable dust concentration may be a valuable predictor for personal
      endotoxin concentration in the sites studied. CONCLUSIONS: Workers at composting
      sites are exposed to high levels of bacterial endotoxin consistent with adverse
      respiratory outcomes even though in most cases, their personal dust exposure is
      below the suggested regulatory levels. Dose-response data for the biological
      components present in the dust encountered at composting sites are not well
      established at this time and site operators should adopt precautionary measures
      when assessing and managing these potential risks.

PMID- 21087851
TI  - The effect of bed properties on methane removal in an aerated biofilter--model
      studies.
AB  - The capacity of laboratory-scale aerated biofilters to oxidize methane was
      investigated. Four types of organic and mineral-organic materials were flushed
      with a mixture of CH(4), CO(2) and air (1:1:8 by volume) during a six-month
      period. The filter bed materials were as follows: (1) municipal waste compost,
      (2) an organic horticultural substrate, (3) a composite of expanded perlite and
      compost amended with zeolite, and (4) the same mixture of perlite and compost
      amended with bentonite. Methanotrophic capacity during the six months of the
      experiment reached maximum values of between 889 and 1036 gm(-2)d(-1). Batch
      incubation tests were carried out in order to determine the influence of methane
      and oxygen concentrations, as well as the addition of sewage sludge, on
      methanotrophic activity. Michaelis constants K(M) for CH(4) and O(2) were 4.6
      14.9%, and 0.7-12.3%, respectively. Maximum methanotrophic activities V(max) were
      between 1.3 and 11.6 cm(3)g(-1)d(-1). The activity significantly increased when
      sewage sludge was added. The main conclusion is that the type of filter bed
      material (differing significantly in organic matter content, water-holding
      capacity, or gas diffusion coefficient) was not an important factor in
      determining methanotrophic capacity when oxygen was supplied to the biofilter.

PMID- 21087849
TI  - Protein misfolding disorders and macroautophagy.
AB  - A large group of diseases, termed protein misfolding disorders, share the common
      feature of the accumulation of misfolded proteins. The possibility of a common
      mechanism underlying either the pathogenesis or therapy for these diseases is
      appealing. Thus, there is great interest in the role of protein degradation via
      autophagy in such conditions where the protein is found in the cytoplasm. Here we
      review the growing evidence supporting a role for autophagic dysregulation as a
      contributing factor to protein accumulation and cellular toxicity in certain
      protein misfolding disorders and discuss the available evidence that upregulation
      of autophagy may be a valuable therapeutic strategy.

PMID- 21087852
TI  - Development and application of a real-time capacitive sensor.
AB  - A real-time capacitive sensor based on a potentiostatic step method was
      developed. It can display in real-time the evoked current waveform, capacitance
      and the electrical resistance of elements serially connected to the insulation
      layer on the electrode as a function of time as well as the ohmic resistance of
      the insulation layer. These features enable the user to observe the association
      and dissociation of the affinity binding pairs and to evaluate the insulating
      property of the electrode surface during measurement. The system allows the
      setting of potential pulse height, pulse interval, gain, filter, and sampling
      frequency, enabling the system to be more flexible. The performance of the system
      was firstly evaluated with equivalent circuits. Under suitable parameter settings
      it provided good accuracy of both the capacitance and resistance. Using the
      affinity binding pair of human serum albumin (HSA) and anti human serum albumin
      (anti-HSA) the measured capacitance change was used for the direct detection of
      HSA. The developed system provided the same sensitivity as the commercially
      available potentiostat (P>0.05). The proposed system was then applied to analyse
      HSA in real urine samples and the results agreed well with the
      immunoturbidimetric assay (P>0.05). The proposed system can be applied for
      capacitance measurement to directly detect other target analytes using different
      affinity binding pairs. Other applications such as kinetics analysis of the
      interaction between affinity bindings, thickness analysis, and the study of the
      insulation property of the modified layer are also promising.

PMID- 21087853
TI  - A genome-wide perspective on the response and tolerance to food-relevant stresses
      in Saccharomyces cerevisiae.
AB  - The success of food and beverage production processes carried out by
      Saccharomyces cerevisiae and the thriving of food spoilage fungi are dependent on
      the ability of a cell to cope with the many environmental insults imposed during
      food production and preservation processes. Post-genomic approaches, especially
      transcriptomics, proteomics and chemogenomics, applied to S. cerevisiae made
      possible the unveiling of general and specific genome-wide adaptive response
      programs against stress induced by weak acids, ethanol, sulfite, heat and cold
      shock, osmotic pressure and nutrient limitation. These programs and the
      underlying signaling pathways are overviewed herein, highlighting the recent
      identification of genes and pathways found to be involved in stress response and
      tolerance. These are good candidate targets for genetic engineering aiming at the
      development of improved strains. The extension of the data gathered in S.
      cerevisiae to food spoilage fungi is considered. The relevance of the different
      genome-wide approaches in this context is also discussed.

PMID- 21087854
TI  - Chromatin: a molecular interface between cancer and aging.
AB  - To prevent cancer, mammals have evolved potent tumor suppression mechanisms,
      including senescence and apoptosis. These processes depend on regulation of
      chromatin. Chromatin-dependent tumor suppressor pathways are activated in
      premalignant cells and tissues harboring cancer-causing genetic alterations, and
      also in normal aged tissue, the latter likely due to accumulation of genetic and
      cellular damage. Paradoxically, however, disruption of chromatin structure may
      also promote cancer. Apparent defects in chromatin structure accumulate with age,
      the biggest single risk factor for cancer. Evidence suggests that these age
      associated perturbations in chromatin structure contribute to the age-associated
      increase in incidence of cancer. Thus, alterations in chromatin structure can
      both suppress and promote the onset of cancer, and both activities are
      inextricably linked to aging.

PMID- 21087856
TI  - Prognostic value of serial blood S100B determinations in stage IIB-III melanoma
      patients: a corollary study to EORTC trial 18952.
AB  - S100B is a prognostic factor for melanoma as elevated levels correlate with
      disease progression and poor outcome. We determined its prognostic value based on
      updated information using serial determinations in stage IIb/III melanoma
      patients. 211 Patients who participated in the EORTC 18952 trial, evaluating
      efficacy of adjuvant intermediate doses of interferon alpha2b (IFN) versus
      observation, entered a corollary study. Over a period of 36 months, 918 serum
      samples were collected. The Cox time-dependent model was used to assess
      prognostic value of the latest (most recent) S100B determination. At first
      measurement, 178 patients had S100B values <0.2 MUg/l and 33 >= 0.2 MUg/l. Within
      the first group, 61 patients had, later on, an increased value of S100B (>= 0.2
      MUg/l). An initial increased value of S100B, or during follow-up, was associated
      with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B >=
      0.2 versus S100B < 0.2 was 5.57 (95% confidence interval (CI) 3.81-8.16), P <
      0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb
      patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage
      III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI
      4.50-10.16). Similar results were observed regarding overall survival (OS).
      Serial determination of S100B in stage IIb-III melanoma is a strong independent
      prognostic marker, even stronger compared to stage and number of positive lymph
      nodes. The prognostic impact of S100B >= 0.2 MUg/l is more pronounced in stage
      III disease compared with stage IIb.

PMID- 21087855
TI  - Genetic dissection of synaptic specificity.
AB  - Nervous systems are built of a myriad of neurons connected by an even larger
      number of synapses. While it has been long known that neurons specifically select
      their synaptic partners among many possible choices during development, we only
      begin to understand how they make those decisions. Recent findings have started
      to elucidate the molecular mechanisms underlying synaptic target selection
      including positive as well as negative cues from synaptic partners, intermediate
      targets and surrounding tissues. Furthermore, emerging evidence suggests that
      synaptic connections are not only formed among specific sets of neurons, but also
      targeted to specific subcellular domains. Finally, spatial and temporal
      transcriptional regulation of these molecular cues represents an additional,
      versatile mechanism to provide wiring specificity.

PMID- 21087857
TI  - The excess burden of side-effects from treatment in men allocated to screening
      for prostate cancer. The Goteborg randomised population-based prostate cancer
      screening trial.
AB  - BACKGROUND: The number of men needed to treat to prevent one death is rather high
      in prostate cancer screening. How this affects the burden of treatment-related
      side-effects is unclear. The aim of this study was to evaluate the treatment
      related morbidity following radical prostatectomy in men participating in the
      Goteborg randomised population-based prostate cancer screening trial. METHODS: In
      1995, 20,000 men aged 50-64 years were randomly allocated (1:1) to biennial PSA
      screening or to a control group not invited. A subset of prostate cancer patients
      undergoing radical prostatectomy between 2001 and 2008 responded to
      questionnaires preoperatively and at 18 months postoperatively. The primary
      endpoint was patient-reported frequencies of erectile dysfunction as measured by
      the validated International Index of Erectile Function-5 questionnaire and
      urinary incontinence as assessed by use of pads. Analyses were made according to
      intention to screen. FINDINGS: After 14 years of follow-up, a total of 1849 men
      were detected with prostate cancer (1138 screened versus 711 controls, excluding
      7 cancers detected at autopsy in the control group). Overall, 1047 received
      treatment with curative intent and radical prostatectomy was performed in 829
      cases (79.2%). In this study, 294 of these men participated (205 screened and 89
      controls). Of preoperatively potent men 79.1% (91/115) in the screening-group and
      90.7% (49/54) in the control-group became impotent or sexually inactive 18 months
      postoperatively, whereas 14.3% (29/203) of screened men and 20.5% (18/88) of
      controls were considered postoperatively incontinent (regular use of pads).
      Extrapolated data yields that 120/10,000 more men become impotent and 25/10,000
      more men will have the need of pads among men invited to regular PSA screening.
      The 'cost' per life saved at the same follow-up of screening is four men impotent
      and less than one man incontinent. INTERPRETATION: Despite the relatively high
      risk of erectile dysfunction and incontinence following radical prostatectomy for
      prostate cancer, the excess burden of permanent side-effects after population
      based screening can be regarded as relatively low, when related to the number of
      men saved from prostate cancer death. These data can be useful when calculating
      the harms and benefits of screening. However, the outcome on a population-level
      may differ from the benefit for the individual.

PMID- 21087858
TI  - Sulfide enhances methanogenesis in nitrate-containing methanogenic cultures.
AB  - The effects of sulfide on nitrate reduction and methanogenesis using butyrate as
      a carbon source were investigated in a mixed mesophilic, methanogenic culture. In
      the sulfide-free medium, 25-75 mg l(-1) nitrate markedly inhibited the
      efficiencies of acetogenesis and methanogenesis processes. Adding 25 mg-S l(-1)
      increased methane production in nitrate-amended medium. Low sulfide levels
      shifted the nitrate reduction pathway from denitrification to dissimilatory
      nitrate reduction to ammonia (DNRA), thereby reducing the amounts of toxic nitric
      oxide and nitrous oxide produced that inhibit methanogenesis. The dose of 25 mg
      l(-1) sulfide was oxidized completely, during which heterotrophic DNRA
      predominated. The oxidized forms of sulfide reformed, limiting induction of the
      heterotrophic denitrification pathway. The actions of heterotrophic and
      autotrophic DNRA bacteria, denitrifiers, sulfate-reducing bacteria and
      methanogens mitigate nitrate toxicity during methanogenesis in an anaerobic
      process.

PMID- 21087859
TI  - Antitumor agents 281. Design, synthesis, and biological activity of substituted 4
      amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one analogs (ATBO) as potent in
      vitro anticancer agents.
AB  - In our exploration of new biologically active chemical entities, we designed and
      synthesized a novel class of antitumor agents, substituted 4-amino-7,8,9,10
      tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogs. We evaluated their cytotoxic
      activity against seven human tumor cell lines from different tissues, and
      established preliminary structure-activity relationships (SAR). All analogs,
      except 8, 9, and 25-27, displayed potent tumor cell growth inhibitory activity.
      Especially, compounds 15 and 33 with a 4-methoxyphenyl group at position C-4 were
      extremely potent with ED(50) values of 0.008-0.064 and 0.035-0.32 MUM,
      respectively. Compound 15 was the most potent analog compared with structurally
      related neo-tanshinlactone (e.g., 1) and 4-amino-2H-benzo[h]chromen-2-one (ABO,
      e.g., 4) analogs, and thus merits further exploration as an anti-cancer drug
      candidate.

PMID- 21087860
TI  - Design and efficient synthesis of A-278637 derivatives as potential potassium
      channel opener.
AB  - A series of thieno[3,2-b]quinoline derivatives designed based on A-278637
      scaffold, were synthesized efficiently via one-pot three-component reaction under
      solvent-free and catalyst-free conditions. This work provides a new compound
      library with potential biological activity for biomedical screening.

PMID- 21087861
TI  - Discovery of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors
      of HIV-1 capsid assembly.
AB  - The discovery of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of
      inhibitors of HIV-1 capsid assembly is described. Synthesis of analogs of the 1,5
      dihydrobenzo[b][1,4]diazepine-2,4-dione hit established structure-activity
      relationships. Replacement of the enamine functionality of the hit series with
      either an imidazole or a pyrazole ring led to compounds that inhibited both
      capsid assembly and reverse transcriptase. Optimization of the bicyclic
      benzodiazepine scaffold to include a 3-phenyl substituent led to lead compound
      48, a pure capsid assembly inhibitor with improved antiviral activity.

PMID- 21087862
TI  - Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: synthesis, SAR,
      PK/PD and activity in a preclinical model of rheumatoid arthritis.
AB  - The synthesis, structure-activity relationships (SAR) and biological evaluation
      of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was
      determined to be orally efficacious in a murine model of rheumatoid arthritis.

PMID- 21087864
TI  - Two dimeric lignans with an unusual alpha,beta-unsaturated ketone motif from
      Zanthoxylum podocarpum and their inhibitory effects on nitric oxide production.
AB  - Two new dimeric lignans, zanthpodocarpins A (1) and B (2), and five known
      lignans, eudesmin (3), (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4
      dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (4), dimethoxysamin (5), rel
      (1R,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octan-2-one (6),
      and magnone A (7), were isolated from the barks of Zanthoxylum podocarpum. Their
      structures were identified by using spectroscopic methods. Compounds 1 and 2 are
      rare dilignans bearing an unusual alpha,beta-unsaturated ketone group from a
      natural source. Bioassay showed that compounds 1 and 2 could inhibit nitric oxide
      (NO) production in LPS stimulated RAW 264.7 cells with IC(50) values of 5.31 MUM
      and 12.15 MUM, respectively.

PMID- 21087863
TI  - Synthesis and biological characterisation of novel dithiocarbamate containing 5
      nitroimidazole (99m)Tc-complexes as potential agents for targeting hypoxia.
AB  - With the aim to develop new potential (99m)Tc-radiopharmaceuticals for imaging
      hypoxia based on the formation of Tc-nitrido complexes, two novel dithiocarbamate
      containing metronidazole derivatives (L1 and L2) have been prepared and
      characterised. The synthesis of L1 and L2 was achieved in excellent yield and
      high purity. Labelling with (99m)Tc was successfully performed using a low ligand
      concentration (approximately 2-3mg) and the desired products were obtained with
      high radiochemical purity (>90%). Lipophilicity, plasma protein binding, and
      biodistribution in normal- and tumour-bearing-CD1 mice studies were performed to
      asses the potentiality for nuclear medicine oncology. According to the
      physicochemical and biological behaviour both in healthy animals and in animals
      bearing solid tumours complex dtcTc1 could be considered as a starting point for
      the development of new radiopharmaceuticals for imaging hypoxia.

PMID- 21087865
TI  - Assessing and training standing balance in older adults: a novel approach using
      the 'Nintendo Wii' Balance Board.
AB  - Older adults, deemed to be at a high risk of falling, are often unable to
      participate in dynamic exercises due to physical constraints and/or a fear of
      falling. Using the Nintendo 'Wii Balance Board' (WBB) (Nintendo, Kyoto, Japan),
      we have developed an interface that allows a user to accurately calculate a
      participant's centre of pressure (COP) and incorporate it into a virtual
      environment to create bespoke diagnostic or training programmes that exploit real
      time visual feedback of current COP position. This platform allows researchers to
      design, control and validate tasks that both train and test balance function.
      This technology provides a safe, adaptable and low-cost balance training/testing
      solution for older adults, particularly those at high-risk of falling.

PMID- 21087866
TI  - Age-related effects of a memorizing spatial task in the adults and elderly
      postural control.
AB  - The aim of this study was to evaluate the age-related changes in postural control
      during a simple quiet standing task and a dual-task paradigm (applying a memory
      spatial task and quiet standing). Thirty-five subjects were divided in two age
      related groups: both younger (Y: 20-26 years) and older (O: 60-77 years) groups
      performed a simple postural task (quiet standing) and a dual-task (a visual
      memory task combined with quiet standing). Measures of the center of pressure
      (CoP) were recorded and its two components, the center of gravity (CG) and the
      differential CoP-CG, were evaluated. An age-related effect was observed in static
      postural performance during dual-tasking. Postural stability led to improved
      performance in younger subjects during the dual-task and but not in the elderly.
      Of the results suggest there is a "cognition first" principle for the younger
      adults, that is, the mirror image of the "posture first" principle observed in
      older adults under dual-tasking situations.

PMID- 21087867
TI  - Synthesis and SAR study of new phenylimidazole-pyrazolo[1,5-c]quinazolines as
      potent phosphodiesterase 10A inhibitors.
AB  - A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a-q was designed,
      synthesized and characterised as a novel class of potent phophodiesterase 10A
      (PDE10A) inhibitors. In this series, 2,9-dimethyl-5-(2-(1-methyl-4-phenyl-1H
      imidazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline (1q) showed the highest affinity
      for PDE10A enzyme (IC(50)=16nM).

PMID- 21087868
TI  - In silico discovery of acylated flavonol monorhamnosides from Eriobotrya japonica
      as natural, small-molecular weight inhibitors of XIAP BIR3.
AB  - Targeting the baculoviral inhibitor of apoptosis proteins repeat (BIR) 3 of X
      linked inhibitor of apoptosis proteins (XIAP) represents an innovative strategy
      for the design of chemosensitizers. Acylated flavonol monorhamnosides (AFMR) from
      Eriobotrya japonica Lindl. (Rosaceae) were virtually predicted as ligands of the
      XIAP BIR3 domain by using a previously generated pharmacophore model. From the
      methanol leaf extract of E. japonica an enriched mixture of AFMR was obtained
      showing chemosensitizing potential in combination with etoposide in XIAP
      overexpressing Jurkat cells. The HPLC-SPE-NMR hyphenated technique facilitated
      the structure elucidation of three known and two new natural AFMR. The main
      constituent and virtual hit, kaempferol-3-O-alpha-l-(2",4"-di-E-p-coumaroyl)
      rhamnoside (3) was isolated from the enriched fraction. Applying a fluorescence
      polarization based binding assay, 3 was identified as XIAP BIR3 ligand with a
      dose-dependent affinity (IC50 10.4 MUM). Further, 3 induced apoptosis in XIAP
      overexpressing Jurkat cells and activated caspase-9 in combination with
      etoposide. Docking experiments revealed a major impact of the coumaric acid and
      sugar moieties of 3 on XIAP BIR3 binding, which was experimentally confirmed. To
      conclude, this study elucidates 3 as natural, small-molecular weight XIAP BIR3
      inhibitor using a combination of in silico and HPLC-SPE-NMR hyphenated
      techniques.

PMID- 21087869
TI  - Assessing the structure and function of single biomolecules with scanning
      transmission electron and atomic force microscopes.
AB  - The scanning transmission electron microscope (STEM) and the atomic force
      microscope (AFM) have provided a wealth of useful information on a wide variety
      of biological structures. These instruments have in common that they raster-scan
      a probe over a sample and are able to address single molecules. In the STEM the
      probe is a focused electron beam that is deflected by the scan-coils. Detectors
      collecting the scattered electrons provide quantitative information for each sub
      nanometer sized sample volume irradiated. These electron scattering data can be
      reconstituted to images of single macromolecules or can be integrated to provide
      the mass of the macromolecules. Samples need to be dehydrated for such
      quantitative STEM imaging. In contrast, the AFM raster-scans a sharp tip over a
      sample surface submerged in a buffer solution to acquire information on the
      sample's surface topography at sub-nanometer resolution. Direct observation of
      function-related structural changes induced by variation of temperature, pH,
      ionic strength, and applied force provides insight into the structure-function
      relationship of macromolecules. Further, the AFM allows single molecules to be
      addressed and quantitatively unfolded using the tip as nano-tweezers. The
      performance of these two scanning probe approaches is illustrated by several
      examples including the chaperonin GroEL, bacterial surface layers, protein
      crystals, and bacterial appendices.

PMID- 21087870
TI  - Prevalence and clinical significance of elevated preoperative glycosylated
      hemoglobin in diabetic patients scheduled for coronary artery surgery.
AB  - OBJECTIVE: To establish what is the prevalence of elevated HbA1c among diabetic
      patients scheduled for coronary surgery and whether this may influence their
      postoperative outcome. METHODS: We performed a retrospective review of our
      departmental cardiac surgical database over a 3-year period (2006-2008). Among
      the 2665 patients, who underwent coronary revascularization, 782 (29.3%) patients
      had diabetes mellitus, with 735 (94.0%) patients having their HbA1c assessed
      preoperatively up to 3 days before the start of the procedure. Patients with
      preoperative normal or elevated HbA1c (>7%) were compared regarding their
      hospital mortality, morbidity (defined as any postoperative complication such as
      stroke, renal failure, wound infection, perioperative myocardial infarction (MI),
      and others) as well as mean intensive care unit (ICU) and hospital stay. Patients
      for comparisons were matched to achieve similar preoperative status with a use of
      a Greedy matching procedure. Chi-square test was performed to compare variables
      of interest; p<0.05 was considered significant. RESULTS: Elevated HbA1c levels
      were present in 38.4% of diabetic patients - 57.1% of patients among insulin
      dependent diabetics, 27.3% of patients on oral medication, and in 7.7% of
      patients whose diabetes was treated with diet only. In a direct comparison and
      after matching for preoperative variables, elevated HbA1c levels increased only
      the frequency of perioperative MI (p=0.01). Other complications, length of ICU
      and hospital stay as well as early mortality were similar in both the groups.
      CONCLUSIONS: Elevated HbA1c levels are common among diabetic patients scheduled
      for coronary surgery, particularly in patients receiving insulin, and are
      associated with more frequent occurrence of perioperative MI.

PMID- 21087872
TI  - The electromyographic fatigue threshold is not a valid tool to assess muscle
      function.
AB  - The present study aimed at determining the electromyographic fatigue threshold
      (EMG(FT)) from the EMG activity level and the EMG frequency content of the First
      Dorsal Interosseous. Thirty-seven healthy subjects performed seven isometric
      index abductions at randomly ordered percentages of maximal voluntary contraction
      (i.e., 20%, 25%, 30%, 35%, 40%, 50% and 60%). During these bouts, surface EMG was
      measured using a linear electrodes array (i.e., seven EMG channels) in the First
      Dorsal Interosseous. For each subject the EMG(FT) was determined from both Root
      Mean Square (RMS) and Mean Power Frequency (MPF) values, only if the following
      criteria were met: (i) significant positive linear regression (P<0.05) between
      force and slope coefficient, (ii) an adjusted coefficient of determination for
      force versus slope coefficient relationship greater than 0.85, and (iii) a
      standard error for the EMG(FT) below 5% of MVC. The results showed the inability
      to determine an EMG(FT) in all of the 37 subjects from both RMS (9 out of 37
      subjects) and MPF (27 out of 37 subjects). In addition, for the 12 subjects
      tested twice, the reproducibility of the EMG(FT) determination was weak (ICC=
      0.029 and SEM=7.5% of MVC for EMG(FT) determined from MPF). The present results
      suggest that the EMG(FT) is not a valid tool to assess muscle function.

PMID- 21087873
TI  - Depersonalization: a selective impairment of self-awareness.
AB  - Depersonalization is characterised by a profound disruption of self-awareness
      mainly characterised by feelings of disembodiment and subjective emotional
      numbing. It has been proposed that depersonalization is caused by a fronto-limbic
      (particularly anterior insula) suppressive mechanism--presumably mediated via
      attention--which manifests subjectively as emotional numbing, and disables the
      process by which perception and cognition normally become emotionally coloured,
      giving rise to a subjective feeling of 'unreality'. Our functional neuroimaging
      and psychophysiological studies support the above model and indicate that,
      compared with normal and clinical controls, DPD patients show increased
      prefrontal activation as well as reduced activation in insula/limbic-related
      areas to aversive, arousing emotional stimuli. Although a putative inhibitory
      mechanism on emotional processing might account for the emotional numbing and
      characteristic perceptual detachment, it is likely, as suggested by some studies,
      that parietal mechanisms underpin feelings of disembodiment and lack of agency
      feelings.

PMID- 21087874
TI  - A genetic predisposition for bovine neonatal pancytopenia is not due to mutations
      in coagulation factor XI.
AB  - Bovine neonatal pancytopenia (BNP) is a newly emerging disease in many European
      countries that causes haemorrhagic diathesis and mortality in neonatal calves.
      This study tested the hypothesis that genetic factors might be involved in BNP,
      since genetic defects resulting in coagulation disorders have been described in
      many species, including cattle. A familial pattern of occurrence of BNP cases was
      observed in an experimental population of cattle in Germany and BNP was diagnosed
      in nine calves on an experimental dairy herd from May 2007 to December 2009. All
      affected calves were descendents of a single F(1) sire in a specific F(2)
      resource population generated from Charolais and German Holstein bloodlines.
      Sequence analysis of the bovine coagulation factor XI (F11) gene as a functional
      candidate gene for BNP revealed an unusually high number of non-synonymous
      mutations within the gene compared to a whole genome mutation screen in cattle
      targetting random sequences. However, none of the mutations in the F11 gene were
      concordant with BNP status. Although these data and further pedigree analysis
      excluded a simple mode of inheritance of the BNP phenotype, there was a
      statistically significant (P=0.0001) accumulation of BNP cases in the specific
      pedigree examined, suggesting that a genetic component is involved in the
      development of BNP.

PMID- 21087875
TI  - Epizootic rabbit enteropathy: comparison of PCR-based RAPD fingerprints from
      virulent and non-virulent samples.
AB  - Epizootic rabbit enteropathy is a gastrointestinal disorder of unknown aetiology
      of farmed rabbits characterised by inanition and mortality. Genomic analyses of
      virulent and non-virulent samples of inocula were performed using random
      amplification of polymorphic DNA (RAPD). Differences in bacterial DNA composition
      were found between inocula, but specific sequences were not linked with field
      cases of epizootic rabbit enteropathy.

PMID- 21087876
TI  - [Rate of genotypic mutations and resistance to antiretroviral drugs in a general
      hospital].
AB  - OBJECTIVES: The objective is to describe the resistance mutation rate in protease
      and reverse transcriptase genes and sensitivity to different antiretrovirals in
      our environment. METHODS: We performed an observational descriptive study in
      which we examined the samples provided at the clinical immunology laboratory
      between April 2004 and April 2009. We analysed both the resistance tests and the
      sensitivity to different drugs in patients with therapeutic failure using trugene
      hiv01 genotyping kits((r)). RESULTS: We registered samples from 242 patients, 61
      of which had no detectable resistance. The most prevalent mutations according to
      drug families were: for nucleoside analog reverse transcriptase inhibitors
      T215A/C/D/F/L/N/S/Y (24.10%), M184G/I/V/W (14.66%), M41J/L/R/T/W (11.24%) and
      K219E/G/H/N/R/T/W (10.24%). The highest levels of resistance corresponded to
      stavudine and lamivudine/emtricitabine, and tenofovir produced the least
      resistance in our environment. The non-analogues were K103N/R (23.98%),
      V179D/E/I/M/T (10.82%), A98E/G/S (10.53%) y K101E/P/Q/R (9.06%). Nevirapine
      presented greater resistance than efavirenz. Protease inhibitors were L10F/I/V
      (15.95%), M36I/L (13.81%), A71I/T/V (13.10%) and 154L/S/V (7.38%). The
      combination darunavir/ritonavir combination was that which presented the least
      resistance, and tipranavir/ritonavir and lopinavir/ritonavir the most resistance.
      CONCLUSIONS: Antiretroviral resistance and sensitivity to retroviral treatment in
      our environment was similar to results from other studies in Spain, but differed
      in the high level of resistance to lamivudine/emtricitabine and
      lopinavir/ritonavir.

PMID- 21087877
TI  - Disseminated bone involvement in systemic sarcoidosis mimicking bone metastases.
      A multimodality imaging approach.

PMID- 21087878
TI  - [Use of the vascularized upper tibial crest at the wrist and hand].
AB  - The choice of a technique for reconstruction of bone loss to the lower end of the
      forearm is often difficult, especially in cases of nonunion. Vascularized bone is
      essential in these indications. We present cases of post-traumatic hand and wrist
      reconstruction with upper tibial corticocancellous transfer. It is a reliable
      reconstructive procedure for forearm bone loss to cover limited size bone
      defects, leaving no complication to the donor site.

PMID- 21087879
TI  - [Should we reconstruct the flexor retinaculum in the carpal tunnel?].
AB  - Conflicting data in the literature justify this review about the flexor
      retinaculum (FR). Reconstruction of the FR following carpal tunnel open release
      has been recommended in order to limit the drawbacks of open carpal tunnel
      release; these drawbacks have been reported in wide series of results published
      between 1956 and 1988. This paper includes a review of the literature, a survey
      of the practice of the members of the French society for surgery of the hand
      (GEM), a self-evaluation of grip strength as well as a summary of indications.

PMID- 21087880
TI  - [Vascularized rotatory transfer of the trapezoid-trapeziometacarpal bi-articular
      complex for treatment of severe TMC-joint arthritis].
AB  - A new surgical technique to reconstruct the basal joint of the thumb, to treat
      persistent pain, restore stability and function, due to severe degenerative osteo
      arthritis, is here presented. Our research on the anatomo-topographical and bio
      mechanical aspect of the Trapezium-Trapezoid-Metacarpal bi-articular complex (TM
      TZM) has led us to observe that trapezoid-metacarpal joint (TZM) is a working
      joint, which has remained inactive for many years, a true joint bank for the TM
      joint. When it is transposed at the base of the thumb column, it is obliged to
      move according to the active movements of the intrinsic and the extrinsic
      muscles. Since January 1998, 34 patients have been operated on, replacing the
      trapezio-metacarpal (TM) joint with trapezoid-metacarpal (TZM) joint and vice
      versa. Rotatory transfer of trapezoid-metacarpal pro-trapezio-metacarpal joint
      was achieved preserving entirely the intrinsic ligaments and the dorsal branch of
      the radial artery, which rotates palmarly with the biarticular complex thus
      ensuring vascular supply. Procedure consists in a wrist dorso-radial approach,
      metaphyseal osteotomy of first and second metacarpal bases, capsulotomy all
      around and rotatory transfer of the bi-articular complex, stabilization with K
      wires of osteotomies and capsulo-ligamentous reconstruction. Follow-up evaluation
      of the patients ranged between 3 months and 10 years (mean 4 years). Results have
      been excellent in 24 cases and good in 10. Painless motion, stability due to the
      first metacarpal ray length reconstruction with a subsequent redistribution of
      forces along the entire axis, restored thumb opposition, pinch and grip strength
      of the hand have been obtained. In conclusion, this technique represents now a
      new surgical opportunity for a surgeon to choose a straightforward and reliable
      treatment in a wider range of care for degenerative arthritis or severe and
      destructive trauma of the TMC joint. A greater number of cases and a longer
      follow-up are necessary for a wider evaluation of the procedure.

PMID- 21087881
TI  - [Bone scintigraphy in evaluation of bone vascularisation at wrist and hand].
AB  - Diphosphonate bone scintigraphy is used since the 1970s for studying bone
      pathology; it is increasingly common because of increased physical activity of
      the population. The disphosphonate uptake in bone requires the preservation of
      bone vascularity and reflects osteoblastic activity; it allows studying the
      viability of bone. Using data from the literature and our experience, we tried to
      take stock of its main uses in routine emphasizing the study of vascular and
      describe its use in fractures of the scaphoid and in the study of vascularised
      bone transfers. If the value of scintigraphy is well known, the use made by means
      of pinhole collimator and the market entry of new and more sensitive detectors
      with better resolution could allow the side of the imaging anatomy of improving
      the study of the vascularisation of small bone transfers which are increasingly
      used, particularly at wrist and hand.

PMID- 21087882
TI  - [Zaidemberg's vascularized radial graft].
AB  - In 1991, Carlos Zaidemberg described a new technique to repair scaphoid non
      unions with a vascularized bone graft harvested from the radial styloid process.
      An anatomic study based on 30 dissections after colorized latex injection
      established the constancy of the radial styloid process's artery, while showing
      that its origin, course and length were subject to variations. In a retrospective
      series of 38 cases over a period of 10 years, the vascularized bone graft was
      indicated for: (1) scaphoid non-union with the presence of avascular changes of
      the proximal fragment (23 cases); (2) failed prior reconstruction with bone graft
      and internal fixation (nine cases); (3) degenerative styloid-scaphoid arthritis
      (three cases); (4) fracture on Preiser dystrophy (three cases). The five steps of
      the simplified operative technique without dissection of the vascular pedicle
      include: (1) longitudinal dorso-radial approach, identification of the periosteal
      portion of the radial styloid process artery; (2) incision of the first and
      second compartments, longitudinal arthrotomy under the second compartment; (3)
      styloidectomy and transversal resection of the scaphoid non-union and sclerotic
      bone; (4) elevation of the vascularized bone graft; (5) transversal and radial
      insertion of the vascularized bone graft, osteosynthesis by two or three K-wire
      touching the scaphoid's radial edge. Scaphoid union was obtained in 33 cases out
      of 38. The only postoperative complications were two transient radial
      paresthesia. The standardized surgical procedure using vascularized bone graft
      harvested from the radial styloid process provides an efficient scaphoid
      reconstruction.

PMID- 21087883
TI  - [Free vascularized fibular flap in distal radius reconstruction].
AB  - Free vascularized bone transfers are indicated to reconstruct large bone loss,
      either after traumatism or bone tumor resection. Free vascularized fibular
      transplant is particularly well designed for reconstruction of large defect of
      the distal radius. Anatomy is constant and harvesting is versatile and reliable.
      It may be used as bony transplant alone, osteocutaneous or osteocutaneomuscular.
      The length of the fibula harvested can be up to 25 cm. In children bone
      reconstruction, the proximal physis of the fibula can be transferred to allow
      secondary bone growth but there is a need for double anastomosis of the
      anteriotibial and the fibular bundles. Donor site sequelae are minimal.

PMID- 21087884
TI  - [Pedicled joint transfers in the fingers].
AB  - OBJECTIVES: We report a retrospective series of 27 cases of composite island
      homodigital distal interphalangeal joint to replace proximal destroyed
      interphalangeal joint. Results of our series are compared with other procedures
      available in order to specify the place of pedicled articular transfers mainly
      for the proximal interphalangeal joint which is recognized as the most important
      joint in the finger. METHODS: The series included 27 cases of destroyed proximal
      interphalangeal joints with preservation of the distal interphalangeal joint, the
      flexor tendon and vascular pedicles. The mean age was 32 years, 26 male, all
      manual workers. All fingers were concerned mainly the third (13 cases) and the
      fourth (10 cases). RESULTS: No vascular failure. Pain quotation improved from 7
      preoperatively to 2 postoperatively. Average flexion-extension motion arc was 43
      degrees . The grip strength was 54% compared to the opposite side. The average
      time off work was 7 months. Complications were few, all of them due to technical
      imperfections underlining the difficulty of this procedure. This transfer
      deserves his use due to the better mobility he gives compared to the other
      techniques available. CONCLUSIONS: Reconstruction of important articular loss of
      substance in a digit remains an unsolved problem, especially for the proximal
      interphalangeal joint representing the anatomical and functional center of the
      digit. However, in certain good indications, especially in emergency it deserves
      to be used.

PMID- 21087885
TI  - [An unusual cause of hand nodule: peri-tendon dirofilariasis].
AB  - Dirofilariasis is a zoonosis affecting dogs and cats. It was transmitted to man
      by mosquito bites. Human dirofilariasis is rare. We report a case of 4-year-old
      girl presented with a subcutaneous palmar nodule of the hand. Surgical excision
      shows a nodule encircling the forth flexor tendon. The histological examination
      established the diagnosis by the presence of an adult worm identified as
      Dirofilaria repens. Surgical excision was curative.

PMID- 21087886
TI  - [Distal radius fracture with dorsal displacement: correlation between functional
      score, reduction quality and fixation].
AB  - Appropriate treatment for fractures of the distal radius with dorsal displacement
      remains a subject of debate. Intrafocal pinning is the most widely used technique
      in France. Plate fixation has been developed to avoid secondary displacement and
      stiffness sometimes observed after pinning. We compared three osteosynthesis
      techniques for the same type of fracture (extra-articular with dorsal
      displacement). Sixty-two consecutive patients underwent osteosynthesis using the
      following techniques successively: posterior plates (20 patients mean age 59.9
      years [range 25-87 years]), intra- and extrafocal pinning (22 patients mean age
      55.6 years [range 17-83 years]), the anterior plate (20 patients mean age 57.1
      years [range 17-78 years]). An independent operator evaluated all patients using
      the Herzberg, Gartland and Werley and Dash scores. The radial slope in the
      frontal plane, sagittal tilt, and ulnar variance were measured and compared
      between the preoperative and last follow-up values. Kruskall-Wallis or ANOVA were
      applied as appropriate for continuous variables and the Chi-square test for non
      continuous variables. P<0.05 was considered significant. Mean operative time was
      equivalent for the two plates fixation techniques and twice as long as for
      pinning. There were more complications in the posterior plating group (32%) and
      less satisfactory function score despite a two-fold longer follow-up and a
      smaller number of operators. The best results were obtained with the anterior
      plating group in terms of range of motion (flexion-extension), DASH score,
      preservation of ulnar variance and presence of a largest number of excellent and
      very good outcomes according to Gartland. The pinning group provided the best
      results in terms of sagittal slope. The pinning and anterior plating groups had
      equivalent range of motion for pronation-supination and the same rate of
      complications (5%). Irrespective of the treatment arm, the Herzberg scores and
      the Gartland and Dash scores were better: in men, in patients aged less than 30
      years, in patients with an associated fracture of the apex of the ulnar syloid
      process rather than its base. For these extra-articular fractures, pinning can
      provide good functional results like anterior plating but each treatment has
      advantages that functional analysis detected.

PMID- 21087887
TI  - Medial femoral condyle vascularized bone grafts for scaphoid nonunions.
AB  - Free vascularized bone grafts from the medial femoral condyle provide both
      structural support and blood supply to promote union in the difficult subset of
      scaphoid nonunions complicated by humpback deformity and proximal pole avascular
      necrosis. These nonunions have not consistently achieved union when treated with
      grafts which fail to restore scaphoid geometry or vascularity. The rationale,
      indications, contraindications, technique and results of bone grafting scaphoid
      nonunions with grafts harvested from the medial femoral condyle are presented.

PMID- 21087888
TI  - Vascularized bone grafting from the dorsal distal radius for Kienbock's disease:
      technique, indications and review of the literature.
AB  - The goals of surgical procedures in Kienbock's disease are to preserve wrist
      function, revascularize the necrotic lunate and maintain normal wrist kinematics
      when possible. Of the various treatment options, pedicled vascularized bone
      grafts from the dorsal distal radius permit the transfer of vascularized osseous
      tissue to the necrotic lunate in order to revascularize it. Vascularized bone
      grafting is an attractive alternative to conventional bone grafting by improving
      the local biological environment and thereby promoting revascularization. Recent
      advances in the anatomy and physiology of vascularized pedicled bone grafts have
      increased our ability to apply them to the treatment of Kienbock's disease. The
      purpose of this article is to describe the detailed vascular anatomy of the
      dorsal distal radius, the surgical technique, indications as well as
      contraindications of our preferred method of pedicled vascularized bone grafts of
      Kienbock's disease.

PMID- 21087889
TI  - Evaluation of sleeved implant fixation using a rat model.
AB  - Cementless hip implants have some osteolysis, stress shielding, and/or revision
      problems while the cemented ones have cement fracture problems. To overcome these
      problems, a new concept of implant fixation using a sleeve between the implant
      and the bone is proposed. This is a cementless fixation using a sleeve in place
      of the cement with a press-fit stem. The sleeved implant fixation is compared
      with the conventional cemented fixation by measuring the bone volume fraction and
      interface strength in a rat model. The tapered implant was manufactured using a
      stainless-steel Kirschner-wire with a diameter of 1.6mm, and PEEK
      (polyetheretherketone) was used for the sleeve. The Sprague-Dawley rats had
      implantations in their bilateral diaphyseal cut femurs using cemented and sleeved
      fixation, respectively. The rats were sacrificed at 2, 4, and 12 weeks after the
      implantation, and micro-CT scanning as well as push-out testing were performed.
      There was no significant difference between the cemented fixation and the sleeved
      fixation in areas of both BV/TV (bone volume/total volume) (p=0.838) and the
      apparent interface strength (p=0.530). However, the decrease in the BV/TV over
      time was significant in the cemented fixation (p=0.021) while not in the sleeved
      fixation (p=0.603). The sleeved fixation showed a gain in strength with time
      while the cemented fixation showed a reverse tendency but the difference was not
      significant (p=0.125). The results showed the feasibility of the sleeved fixation
      even though the advantage of sleeved fixation was not clearly confirmed because
      of the small sample size and high variance as well as the suboptimal surface
      finish of the sleeve.

PMID- 21087890
TI  - BION microstimulators: a case study in the engineering of an electronic
      implantable medical device.
AB  - The BION (Bionic Neuron) is a single channel implantable neurostimulator of
      unique design that can be delivered by injection. The development of the BION
      injectable neurostimulators exemplifies a challenging, but well posed medical
      design problem addressed with a successful strategy for prioritizing and
      resolving the biomedical and technological challenges. Though some performance
      requirements required post-evaluation revision, all fundamental goals were
      realized. A small number of significant design corrections occurred because the
      device requirements did not include the full scope of environmental demands. The
      design has spawned a number of variants optimized for diverse biomedical
      applications, and its clinical applications continue to evolve. The BION
      development history demonstrates design successes worth emulating and design
      pitfalls that may be avoidable for future medical device development teams. This
      paper serves as an introduction to the BION microstimulator technology and as an
      analysis of the design process used to develop the early clinical devices.

PMID- 21087891
TI  - Is plant ecology more siliceous than we realise?
AB  - Although silicon occurs in all plants, it is an element that is largely
      overlooked by many plant ecologists and most plant-related research on silicon
      comes from agronomy, archaeology, palaeontology and biogeochemistry. Plant
      silicon has many functions, acting biochemically as silicic acid and physically
      as amorphous silica. It contributes to cell and plant strength and enables plants
      to respond adaptively to environmental stresses. Consequently, plant silicon can
      increase plant fitness in many fundamental aspects of ecology, including plant
      herbivore interactions, light interception, pathogen resistance and alleviation
      of abiotic stresses. Here, we provide an ecological perspective to research
      outcomes from diverse disciplines, showing that silicon is an important element
      in plant ecology that is worthy of greater attention.

PMID- 21087892
TI  - Integrating '-omics' and natural product discovery platforms to investigate
      metabolic exchange in microbiomes.
AB  - The microbiome is an abundance of microorganisms within a host (e.g. human
      microbiome). These microorganisms produce small molecules and metabolites that
      have been shown to affect and dictate the physiology of an individual. Functional
      knowledge of these molecules, often produced for communication or defense, will
      reveal the interplay between microbes and host in health and disease. The vast
      diversity in structure and function of microbiome-associated small molecules
      necessitate tools that will utilize multiple '-omics' strategies to understand
      the interactions within the human microbiome. This review discusses the
      importance of these investigations and the integration of current '-omics'
      technologies with tools established in natural product discovery in order to
      identify and characterize uncharacterized small molecules in the effort towards
      diagnostic modeling of the human microbiome.

PMID- 21087893
TI  - The SNO-proteome: causation and classifications.
AB  - Cell signaling is a complex and highly regulated process. Post-translational
      modifications of proteins serve to sense and transduce cellular signals in a
      precisely coordinated manner. It is increasingly recognized that protein S
      nitrosylation, the addition of a nitric oxide group to cysteine thiols, serves an
      important role in a wide range of signaling pathways. In spite of the large
      number of SNO-proteins now identified (~1000), the observed specificity of S
      nitrosylation in terms of target proteins and specific cysteines within modified
      proteins is incompletely understood. Here we review the progress made in S
      nitrosylation detection methods that have facilitated the study of the SNO
      proteome under physiological and pathophysiological conditions, and some factors
      important in determining the SNO-proteome. Classification schemes for emergent
      denitrosylases and prospective 'protein S-nitrosylases' are provided.

PMID- 21087895
TI  - The effects of attention and conscious state on the detection of gaps in long
      duration auditory stimuli.
AB  - OBJECTIVE: To determine the extent to which the detection of a gap occurring in a
      long duration stimulus is affected by attention and conscious state. METHODS: The
      first experiment manipulated the extent to which active processing was required
      for the detection of a 20 ms gap in a 1.4 s duration pure tone stimulus. In a
      second experiment carried out during all-night sleep, a gap was presented in a
      1.5 s noise segment having an intensity of 60 or 80 dB SPL. RESULTS: The gap
      elicited N1 did not significantly vary with the extent of active processing
      during wakefulness. N1 was not elicited by the gap during NREM sleep and was much
      reduced during REM sleep. A large P2 and later N350 was however observed, varying
      directly in amplitude with the intensity of the noise segment. CONCLUSIONS: The
      operations required for the detection of a physical gap function early in
      processing, at a pre-conscious level. SIGNIFICANCE: Attention had relatively
      little effect on the detection of a gap as indexed by the amplitude of N1.
      Detection of a gap also appears to be made during sleep, as indexed by a large
      amplitude P2.

PMID- 21087894
TI  - Proteomic analysis of polyketide and nonribosomal peptide biosynthesis.
AB  - Polyketides and non-ribosomal peptides are in a class of natural products
      important both as drug sources and as dangerous toxins and virulence factors.
      While studies over the last two decades have provided substantial
      characterization of the modular synthases that produce these compounds at the
      genetic level, their understanding at the protein level is much less understood.
      New proteomic platforms called an orthogonal active site identification system
      (OASIS) and proteomic interrogation of secondary metabolism (PrISM) have been
      developed to identify and quantify natural product synthase enzymes. Reviewed
      here, these tools offer the means to discover and analyze modular synthetic
      pathways that are limited by genetic techniques, opening the tools of
      contemporary proteomics to natural product sciences.

PMID- 21087896
TI  - Prevalence and correlates of insomnia in the Swedish population aged 19-75 years.
AB  - OBJECTIVE: To assess the prevalence of insomnia symptoms, their associated
      factors and daytime symptoms in the general population of Sweden. METHODS: This
      is a cross-sectional postal survey performed in the general population of Sweden
      aged between 19 and 75 years (6 million inhabitants). A total of 1209 out of 1705
      randomly selected participants from the National Register of the Total Population
      completed the questionnaire. The participation rate was 71.3%. Participants
      filled out a paper-pencil questionnaire composed of 157 items covering
      sociodemographic characteristics, sleeping habits and environment, sleep quality
      and sleep symptoms, and health status. RESULTS: We found 32.1% (95% confidence
      interval: 29.5-34.8%) of the sample reported having difficulty initiating (DIS)
      or maintaining sleep (DMS) or non-restorative sleep accompanied with sufficient
      sleep (NRS) at least 4 nights per week: 6.3% of the sample had DIS, 14.5% had DMS
      and 18.0% had NRS. Results from logistic regressions showed that restless legs
      symptoms, breathing pauses during sleep and depressive or anxious mood were
      associated with DIS and DMS but not NRS. Living in an urban area (OR:2.0) and
      drinking alcohol daily (OR:4.6) were associated only with NRS. Daytime symptoms
      were reported by over 75% of subjects with insomnia symptoms. DIS, DMS and NRS
      were associated with daytime fatigue but not excessive sleepiness as measured by
      the Epworth scale. DIS was associated with the use of sleeping pills or natural
      sleeping aid compounds in multivariate models. CONCLUSIONS: Insomnia symptoms
      occurring at least 4 nights per week are frequent in Sweden, affecting about a
      third of the population. Subjects with NRS have a distinctly different profile
      than those with DIS or DMS, which suggests different etiological causes for this
      symptom.

PMID- 21087897
TI  - Part 1. International Classification of Functioning, Disability and Health (ICF)
      Core Sets for persons with sleep disorders: results of the consensus process
      integrating evidence from preparatory studies.
AB  - BACKGROUND/OBJECTIVES: The International Classification of Functioning,
      Disability and Health (ICF) provides a comprehensive and universally accepted
      framework to classify changes in functioning related to health conditions.
      Comprehensive and Brief Core Sets have been defined for various disorders but not
      for sleep disorders. Such a Core Set would greatly enhance the techniques
      available to describe the impact of sleep disorders on patients. The overarching
      purpose of this paper is to report on phase 1 of the international and World
      Health Organization (WHO) endorsed consensus process in identifying ICF Core Sets
      for sleep disorders. METHODS: A formal decision-making and consensus process
      which integrated evidence gathered from preparatory studies was carried out.
      Relevant ICF categories were selected by a sample of international experts from
      different backgrounds using the nominal group technique. RESULTS: Twenty-six
      experts from 22 countries and different professional backgrounds attended the
      consensus conference. Altogether 120 second- or third-level ICF categories were
      included in the Comprehensive ICF Core Set with the following ICF component
      split: 49 categories from body functions, 8 from body structures, 31 from
      activities and participation and 32 from environmental factors. The Brief ICF
      Core Set included a total of 15 second-level categories: 5 body functions (sleep,
      energy and drive, attention, consciousness, respiration functions); 3 body
      structures (brain, respiratory system, pharynx); 4 activities and participation
      (focusing attention, driving, handling stress and other psychological demands,
      carrying out daily routine); and 3 environmental factors (immediate family;
      health services, systems, and policies; and health professionals). CONCLUSION: A
      formal consensus process integrating evidence and expert opinion led to the first
      version of the ICF Core Sets for persons with sleep disorders. Further validation
      of the Core Set is needed.

PMID- 21087898
TI  - Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast
      cancer: 10-year analysis of the ATAC trial.
AB  - BACKGROUND: The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial was
      designed to compare the efficacy and safety of anastrozole (1 mg) with tamoxifen
      (20 mg), both given orally every day for 5 years, as adjuvant treatment for
      postmenopausal women with early-stage breast cancer. In this analysis, we assess
      the long-term outcomes after a median follow-up of 120 months. METHODS: We used a
      proportional hazards model to assess the primary endpoint of disease-free
      survival, and the secondary endpoints of time to recurrence, time to distant
      recurrence, incidence of new contralateral breast cancer, overall survival, and
      death with or without recurrence in all randomised patients (anastrozole n=3125,
      tamoxifen n=3116) and hormone-receptor-positive patients (anastrozole n=2618,
      tamoxifen n=2598). After treatment completion, we continued to collect data on
      fractures and serious adverse events in a masked fashion (safety population:
      anastrozole n=3092, tamoxifen n=3094). This study is registered as an
      International Standard Randomised Controlled Trial, number ISRCTN18233230.
      FINDINGS: Patients were followed up for a median of 120 months (range 0-145);
      there were 24,522 woman-years of follow-up in the anastrozole group and 23,950
      woman-years in the tamoxifen group. In the full study population, there were
      significant improvements in the anastrozole group compared with the tamoxifen
      group for disease-free survival (hazard ratio [HR] 0.91, 95% CI 0.83-0.99;
      p=0.04), time to recurrence (0.84, 0.75-0.93; p=0.001), and time to distant
      recurrence (0.87, 0.77-0.99; p=0.03). For hormone-receptor-positive patients, the
      results were also significantly in favour of the anastrozole group for disease
      free survival (HR 0.86, 95% CI 0.78-0.95; p=0.003), time to recurrence (0.79,
      0.70-0.89; p=0.0002), and time to distant recurrence (0.85, 0.73-0.98; p=0.02).
      In hormone-receptor-positive patients, absolute differences in time to recurrence
      between anastrozole and tamoxifen increased over time (2.7% at 5 years and 4.3%
      at 10 years) and recurrence rates remained significantly lower on anastrozole
      than tamoxifen after treatment completion (HR 0.81, 95% CI 0.67-0.98; p=0.03),
      although the carryover benefit was smaller after 8 years. There was weak evidence
      of fewer deaths after recurrence with anastrozole compared with tamoxifen
      treatment in the hormone-receptor-positive subgroup (HR 0.87, 95% CI 0.74-1.02;
      p=0.09), but there was little difference in overall mortality (0.95, 95% CI 0.84
      1.06; p=0.4). Fractures were more frequent during active treatment in patients
      receiving anastrozole than those receiving tamoxifen (451 vs 351; OR 1.33, 95% CI
      1.15-1.55; p<0.0001), but were similar in the post-treatment follow-up period
      (110 vs 112; OR 0.98, 95% CI 0.74-1.30; p=0.9). Treatment-related serious adverse
      events were less common in the anastrozole group than the tamoxifen group (223
      anastrozole vs 369 tamoxifen; OR 0.57, 95% CI 0.48-0.69; p<0.0001), but were
      similar after treatment completion (66 vs 78; OR 0.84, 95% CI 0.60-1.19; p=0.3).
      No differences in non-breast cancer causes of death were apparent and the
      incidence of other cancers was similar between groups (425 vs 431) and continue
      to be higher with anastrozole for colorectal (66 vs 44) and lung cancer (51 vs
      34), and lower for endometrial cancer (six vs 24), melanoma (eight vs 19), and
      ovarian cancer (17 vs 28). No new safety concerns were reported. INTERPRETATION:
      These data confirm the long-term superior efficacy and safety of anastrozole over
      tamoxifen as initial adjuvant therapy for postmenopausal women with hormone
      sensitive early breast cancer.

PMID- 21087899
TI  - Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics.
AB  - Defects in p53 function, which occur frequently in human cancers due to mutations
      in TP53 or disruptions in the p53 regulatory pathway, render cells dependent on
      CHK1 (Checkpoint Kinase 1) to activate cell cycle checkpoints. In the presence of
      DNA damage or replication stress, inhibition of CHK1 leads to "mitotic
      catastrophe" and cell death in p53-deficient tumors while sparing p53-proficient
      cells. CHK1 inhibitors sensitize tumors to a variety of DNA-damaging agents or
      antimetabolites in preclinical models and are being evaluated in early phase
      clinical trials. In this review, we summarize recent advances and controversies
      in the development and application of CHK1 inhibitors as cancer therapeutics.

PMID- 21087900
TI  - NKT cell costimulation: experimental progress and therapeutic promise.
AB  - Invariant natural killer T (iNKT) cells are innate lymphocytes with unique
      specificity for glycolipid antigens and remarkable immunomodulatory properties.
      The role of costimulatory interactions in iNKT cell responses has recently come
      under scrutiny. Although iNKT cells and their prototype glycolipid agonist alpha
      galactosylceramide (alpha-GalCer) have shown promise in several clinical trials
      conducted in patients with cancer or viral diseases, current iNKT cell-based
      therapies are far from effective. The concomitant targeting of T cell receptors
      (TCRs) and costimulatory molecules on iNKT cells represents an exciting new
      opportunity to optimize such therapeutic approaches. Here, we review recent
      advances in our understanding of iNKT cell costimulation and discuss potential
      treatment modalities based on the responsiveness of iNKT cells to disease
      tailored glycolipids and select costimulatory ligands.

PMID- 21087902
TI  - A new regimen of bowel preparation for PillCam colon capsule endoscopy: a pilot
      study.
AB  - BACKGROUND: Colon capsule endoscopy (CCE) represents a new diagnostic, endoscopic
      technology for colonic exploration. Current protocols of preparation led to
      discordant rates of adequate cleansing level or CCE excretion. AIM: To evaluate
      the effect of a new regimen of bowel preparation for CCE on colon cleansing
      levels and on rate of capsule excretion. STUDY: 60 patients were prospectively
      enrolled. The new regimen of preparation consisted of a split regimen of PEG
      administration and of a 45 mL dose of sodium phosphate (NaP). Four senna tablets
      and a low-residue diet were also included. CCE excretion rate, colon cleansing,
      and accuracy were assessed. RESULTS: Forty-six patients were included in the
      final analysis, 13 patients (22%) being excluded because of preparation protocol
      deviations and one due to CCE technical failure (2%). At CCE, bowel preparation
      was rated as good in 78% of patients, fair in 20% and poor in 2%. CCE excretion
      rate occurred in 83% of patients. CCE sensitivity and specificity for significant
      findings was 100% and 95%, respectively. CONCLUSIONS: The combination of a split
      dose of PEG solution with a low dose of NaP boosters resulted in high rates of
      adequate cleansing level and CCE excretion.

PMID- 21087901
TI  - Nanotechnology for synthetic high-density lipoproteins.
AB  - Atherosclerosis is the disease mechanism responsible for coronary heart disease
      (CHD), the leading cause of death worldwide. One strategy to combat
      atherosclerosis is to increase the amount of circulating high-density
      lipoproteins (HDL), which transport cholesterol from peripheral tissues to the
      liver for excretion. The process, known as reverse cholesterol transport, is
      thought to be one of the main reasons for the significant inverse correlation
      observed between HDL blood levels and the development of CHD. This article
      highlights the most common strategies for treating atherosclerosis using HDL. We
      further detail potential treatment opportunities that utilize nanotechnology to
      increase the amount of HDL in circulation. The synthesis of biomimetic HDL
      nanostructures that replicate the chemical and physical properties of natural HDL
      provides novel materials for investigating the structure-function relationships
      of HDL and for potential new therapeutics to combat CHD.

PMID- 21087904
TI  - Linkage and linkage disequilibrium analysis of X-STRs in Italian families.
AB  - Twenty X-chromosomal short tandem repeat (STR) loci were typed in 80 families of
      Italian descent, composed by mother and two or more sons, for a total of 93
      meiosis. The analyzed X-STR panel included six clusters of closely linked markers
      (each spanning<3cM): DXS10135-DXS10148-DXS8378 (Xp22); DXS7132-DXS10074-DXS10079
      (Xq12); DXS6801-DXS6809-DXS6789 (Xq21); DXS7424-DXS101 (Xq22); DXS10103-HPRTB
      DXS10101 (Xq26); DXS8377-DXS10134-DXS7423-DXS10146 (Xq28). Recombination
      fractions between pairs of markers calculated by pedigree analysis were compared
      with those obtained from the second-generation Rutgers combined linkage-physical
      map of the human genome. The observed differences confirm that recombination is
      not homogeneous along the X chromosome and that the conventional subdivision of X
      STRs in four groups of completely unlinked markers cannot be regarded as true.
      Significant linkage disequilibrium was found between markers DXS6801 and DXS6809
      (p=0.017). The effect on likelihood calculations of inferring haplotype
      frequencies from allele distributions rather than haplotype count in the relevant
      population was evaluated.

PMID- 21087905
TI  - Early prediction of femoral head avascular necrosis following neck fracture.
AB  - Femoral neck fracture puts at risk functional prognosis in young patients and can
      be life-threatening in the elderly. The present study reviews methods of femoral
      head vascularity assessment following neck fracture, to address the following
      issues: what is the risk of osteonecrosis? And what, in the light of this risk,
      is the best-adapted treatment to avoid iterative surgery? Femoral head
      vascularity depends on retinacular vessels and especially the lateral epiphyseal
      artery, which contributes from 70 to 80% of the femoral head vascular supply.
      Fracture causes vascular lesions, which are in turn the prime cause of necrosis.
      Other factors combine with this: hematoma tamponade effect, reduced joint space
      and increased pressure due to lower extremity positioning in extension/internal
      rotation/abduction during surgery. Head deformity is not due to direct cell death
      but to the repair process originating from the surrounding living bone. In post
      traumatic necrosis, proliferation rapidly invades the head, with significant
      osteogenesis. Pathologic fractures occur at the boundary between the new and dead
      bone. Many techniques have been reported to help assess residual hemodynamics and
      risk of necrosis. Some are invasive: superselective angiography, intra-osseous
      oxygen pressure measurement, or Doppler-laser hemodynamic measurement; others
      involve imaging: scintigraphy, conventionnal or dynamic MRI. The future seems to
      lie with dynamic MRI, which allows a new classification of femoral neck
      fractures, based on a non-invasive assessment of femoral head vascularity.

PMID- 21087903
TI  - The interaction between the superhero ideal and maladaptive perfectionism as
      predictors of unhealthy eating attitudes and body esteem.
AB  - Unhealthy eating attitudes and poor body esteem often lead to adverse outcomes
      (e.g., eating disorders). Prior research has identified two risk factors for
      these outcomes--endorsement of the superhero ideal and maladaptive perfectionism-
      and has suggested that these factors may interact to predict unhealthy eating
      attitudes and body esteem. The current study examined the interaction between the
      superhero ideal and maladaptive perfectionism as predictors of unhealthy eating
      attitudes and body esteem among 161 12- to 14-year-olds (74 males, 87 females).
      Maladaptive perfectionism moderated the relation between endorsement of the
      superhero ideal and unhealthy eating attitudes for girls only, such that
      endorsement of the superhero ideal was significantly associated with unhealthy
      eating attitudes only for adolescents with high levels of maladaptive
      perfectionism. The moderation model was not significant for body esteem.
      Prevention strategies should focus on reducing endorsement of the superhero ideal
      when there are high levels of maladaptive perfectionism.

PMID- 21087906
TI  - Function and quality of life following medial unicompartmental knee arthroplasty
      in patients 60 years of age or younger.
AB  - INTRODUCTION: UKA is an appropriate bone-sparing solution for focal advanced knee
      osteoarthritis in young patients. As the expectations of patients younger than 60
      years of age are different from those in an older population, we aimed to
      evaluate quality of life and the quality of sports activity after UKA in this
      population. PATIENTS AND METHODS: Sixty-five UKAs in 62 patients younger than 60
      (mean age: 54.7 years; mean BMI: 28 kg/m(2)) performed between 1989 and 2006 were
      included. At last follow-up (minimum 2 years), before the objective evaluation,
      patients were asked to fill in a KOOS questionnaire and a specific sports
      questionnaire including the UCLA score and questions from the Mohtadi score.
      RESULTS: With a mean follow-up of 11.2+/-5 years (range, 2-19 years), the KOOS
      score was higher than 75 points in 90% of the patients for the quality-of-life
      categories but also for the score's four other categories: 83.4% of the patients
      had resumed their sports activities and the mean UCLA score was 6.8 (range, 4-9);
      90% of the patients reported no or slight limitation during sports activities.
      The function KSS improved from 52+/-4 to 95+/-3 points postoperatively and the
      Knee KSS from 50+/-4 to 94+/-4 points. With three patients undergoing revision
      for an isolated insert exchange, one for septic loosening and three for
      osteoarthritis in the external compartment, the 12-year Kaplan-Meier survivorship
      was 94%. DISCUSSION AND CONCLUSION: These results confirmed that UKA can provide
      good patient-rated outcomes, which is very important in this demanding
      population. As for TKA, wear remains a problem in this active population. LEVEL
      OF EVIDENCE: Therapeutic study, level IV.

PMID- 21087907
TI  - Thyroplasty for unilateral vocal fold paralysis using an adjustable implant in
      porous titanium.
AB  - OBJECTIVES: The aim of this study was to describe a new porous titanium
      thyroplasty implant that can be adjusted with a screw. MATERIAL AND METHODS:
      Retrospective study of 15 patients with unilateral vocal fold paralysis
      undergoing type I thyroplasty under local anaesthesia. Each patient's dysphonia
      and swallowing disorders were evaluated both objectively and subjectively before
      and 3 months after thyroplasty. RESULTS: Speech and swallowing disorders were
      improved in all the cases, except when the patients were suffering from severe
      associated neurological disorders (n=3). The postoperative complications were
      minor including a laryngeal edema treated by corticotherapy per os (n=1) and a
      superficial cervical haematoma (n=1). CONCLUSIONS: This implant is easy to insert
      and the results show high tolerance of the biomaterial and above all the
      improvement of functions comparable to other laryngeal implants.

PMID- 21087910
TI  - Preliminary findings on the efficacy of selamectin in the treatment of dogs
      naturally infected with Dirofilaria repens.
AB  - Subcutaneous dirofilariosis caused by Dirofilaria repens is common in dogs and it
      is an emerging helminthozoonosis in Europe, Asia, Africa and also in Hungary.
      Macrocyclic lactones are used for preventing the infection; however, their
      activity against the microfilariae and mature stages of this species is
      questionable. Selamectin is widely used for the prophylaxis of heartworm (D.
      immitis) infection. The objective of the present study was to test the
      microfilaricidal efficacy of the topical formulation of selamectin in dogs
      naturally infected with D. repens . A total of 78 Beagle dogs were examined for
      the presence of circulating microfilariae by Knott's test. Twenty-three of the
      microfilaraemic dogs were divided into four groups and included in the trial. The
      dogs received monthly or biweekly selamectin treatment and were subjected to
      monthly blood testing for a period of 252 or 336 days. At the end of the study,
      65% of the dogs were not microfilaraemic and the rest had low number of
      microfilariae in their blood. These results indicate that chronic spot-on
      selamectin treatment may be a useful tool also in the control of canine
      subcutaneous dirofilariosis.

PMID- 21087909
TI  - Diesel particulate matter induces receptor for advanced glycation end-products
      (RAGE) expression in pulmonary epithelial cells, and RAGE signaling influences NF
      kappaB-mediated inflammation.
AB  - BACKGROUND: Receptors for advanced glycation end-products (RAGE) are cell-surface
      receptors expressed by alveolar type I (ATI) epithelial cells and are implicated
      in mechanisms of alveolar development and sustained pulmonary inflammation.
      OBJECTIVES: In the present study, we tested the hypothesis that diesel
      particulate matter (DPM) up-regulates RAGE in rat ATI-like R3/1 cells and human
      primary small airway epithelial cells (SAECs), leading to an inflammatory
      response. METHODS AND RESULTS: Using real-time reverse transcriptase polymerase
      chain reaction and immunoblotting, we found that RAGE mRNA and protein are up
      regulated in cells exposed to DPM for 2 hr. Use of a luciferase reporter
      containing nuclear factor-kappaB (NF-kappaB) response elements revealed decreased
      NF-kappaB activation in cells transfected with small interfering RNA (siRNA) for
      RAGE (siRAGE) before DPM exposure compared with cells transfected with scrambled
      control siRNA (siControl). In addition, immunostaining revealed diminished
      nuclear translocation of NF-kappaB in DPM-exposed cells transfected with siRAGE
      compared with cells transfected with siControl before DPM stimulation. Enzyme
      linked immunosorbent assay demonstrated that in R3/1 cells DPM induced secretion
      of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), two
      cytokines induced by NF-kappaB and associated with leukocyte chemotaxis during an
      inflammatory response. Incorporating siRAGE was sufficient to significantly
      decrease DPM-induced MCP-1 and IL-8 secretion compared with cells transfected
      with siControl. CONCLUSIONS: These data offer novel insights into potential
      mechanisms whereby RAGE influences pulmonary inflammation exacerbated by DPM
      exposure. Further research may demonstrate that molecules involved in RAGE
      signaling are potential targets in lessening the degree of particulate matter
      induced exacerbations of inflammatory lung disease.

PMID- 21087911
TI  - Vertebral osteomyelitis and meningomyelitis caused by Pasteurella canis in a dog-
      clinicopathological case report.
AB  - A clinicopathological case study of vertebral osteomyelitis caused by Pasteurella
      canis in a 2.5-year-old male Jack Russell Terrier is presented. The case was
      characterised by a chronic course with signs of spinal pain and acute paraplegia.
      The diagnosis was established by radiography, myelography, post-myelographic CT
      examination, and laboratory tests including routine blood work and cerebrospinal
      fluid (CSF) cytology, and confirmed by postmortem pathological and
      microbiological examinations. Diagnostic imaging showed severe osteolysis,
      ventral spondylosis and spinal cord compression at the 4th and 5th lumbar
      vertebrae. The blood tests revealed mild leukocytosis and anaemia, while CSF
      cytology showed lymphocytic and mononuclear pleocytosis. Necropsy demonstrated
      severe osteomyelitis and meningomyelitis, but the source of infection could not
      be established. To the authors' knowledge, this is the first description of
      canine vertebral osteomyelitis caused by this organism.

PMID- 21087912
TI  - Immunohistochemical detection of arteriolar hyperplasia in canine liver biopsy
      samples using the claudin-5 antibody.
AB  - Claudins are key tight junctional proteins between adjacent epithelial,
      mesothelial or endothelial cells, which are responsible for the permeability of
      the paracellular space. This paper describes that the endothelial cells of normal
      hepatic arterioles, portal venules and portal lymphatics as well as the
      endothelium of sinusoids from dogs show strong membranous claudin-5 cross
      reactivity. In 25 liver biopsy samples taken from dogs with portal vein
      hypoperfusion, an increased number of arterioles was detected in the portal areas
      (PAs) by the use of humanised anti-claudin-5 antibody. The increased number of
      hyperplastic hepatic arterioles per PA was 5-6, 8-12 and 15-20 in the case of
      small, medium-sized and large PAs, respectively. It is suggested that the claudin
      5 marker can improve the detection of hepatic arteriolar proliferation in the PAs
      of liver samples.

PMID- 21087913
TI  - In situ complex adenocarcinoma on the femoral part of the hindlimb in an Asian
      Leaf Turtle (Cyclemys dentata).
AB  - A heterotopic in situ complex adenocarcinoma developing on the hindlimb is
      reported for the first time from an Asian Leaf Turtle (Cyclemys dentata). The
      tumour mechanically hampered the movement of the animal. The turtle refused to
      eat and consequently developed a poor condition. Histopathology of the tumour
      revealed all characteristics of a well-differentiated adenocarcinoma originating
      from apocrine gland-like tissue: the irregular, tubular structures varying in
      size were generally lined by two to four layers of cuboidal to columnar
      neoplastic epithelial cells. Claudin-5, pancytokeratin, cytokeratin, vimentin,
      alpha-SMA and Ki-67 immunohistochemical antibodies were employed for
      characterising the tumour. The diagnosis was a complex adenocarcinoma originating
      from apocrine gland-like tissue in a turtle.

PMID- 21087914
TI  - Haemangiomas, leiomyosarcoma and myeloma caused by subgroup J avian leukosis
      virus in a commercial layer flock.
AB  - An outbreak of simultaneously occurring haemangiomas, leiomyosarcoma and myeloma
      was observed in a commercial layer flock in China. The sick chickens were
      extremely thin and dehydrated. Scattered haemangiomas were found on the claws,
      breast and wings. At necropsy, haemangiomas and some other nodular tumours were
      also found in the internal organs. In addition, diffuse enlargement of the liver
      and spleen appeared in some birds. Histopathologically, haemangiomas were
      typically cavernous haemangiomas and haemangioendothelioma. In the diffusely
      swollen liver and spleen, multifocal or widespread marrow tumour cells filled
      with ball-like acidophilic particles in cytosol were observed, which are the
      characteristic pathological changes of avian myelocytomatosis. The nodular tumour
      cells formed by muscle bundles were of variable size, irregular shape, poorly
      differentiated and malaligned. Immunohistochemistry for vimentin, cytokeratin,
      actin (smooth muscle) and actin (sarcomeric) and Masson's staining confirmed the
      different cell lineage of the nodular tumour, thus leading to the diagnosis of
      leiomyosarcoma. The seroprevalence of avian leukosis subgroup J (ALV-J)
      antibodies was 13.46% (7/52), while ALV-A/B and reticuloendotheliosis virus (REV)
      antibodies were not detectable. The DF-1 cells inoculated by virus extracted from
      liver samples from 24 infected chickens were cultured and the group-specific
      antigen (GSA) was identified by ELISA. All samples were positive for ALV, which
      was further identified as ALV-J by immunofluorescence assay (IFA). PCR analysis
      revealed that three isolates of ALV-J proviral sequence were close to the HPRS
      103 prototype strain and other Chinese field strains isolated in recent years,
      while one isolate (DP01) had a lower homology with them. This is the first report
      that ALV-J infection caused the simultaneous occurrence of haemangiomas,
      leiomyosarcoma and myeloma in a commercial layer flock.

PMID- 21087915
TI  - PUFA-dependent alteration of oxidative parameters of a canine mastocytoma cell
      line.
AB  - Mast cells play a key role in the immune response. Thereby, the balance of
      oxidative metabolism is of importance in mast cell mediator synthesis and
      release. Fatty acids may modify mast cell function in several ways. In this
      study, we investigated the influence of polyunsaturated fatty acids (PUFAs) on
      oxidative parameters of a canine mastocytoma cell line. C2 cells were cultured in
      media supplemented with linoleic acid, arachidonic acid, alpha-linolenic acid and
      eicosapentaenoic acid, respectively. Production of reactive oxygen species (ROS)
      as well as lipid peroxides was tested. Furthermore, stressor-induced DNA damage
      was measured. Exposure of the cells to PUFAs resulted in a significant increase
      in the synthesis of both ROS and lipid peroxides. Distinct differences between
      the PUFAs tested underline the impact of the unsaturation degree of fatty acids
      as well as the position of double bonds on mast cells.

PMID- 21087916
TI  - Development of bovine embryos cultured in CR1aa and IVD101 media using different
      oxygen tensions and culture systems.
AB  - The aim of the present study was to optimise the culture conditions for the in
      vitro production of bovine embryos. The development of in vitro fertilised bovine
      oocytes in CR1aa supplemented with 5% calf serum and IVD101 culture media were
      compared using traditional microdrops and Well of the Well (WOW) culture systems
      either under 5% or 20% oxygen tension. After 7 days of culture, a significantly
      higher blastocyst formation rate was obtained for embryos cultured in CR1aa
      medium compared to those cultured in IVD101, irrespective of O2 tensions and
      culture systems. The blastocyst formation in IVD101 was suppressed under 20% O2
      compared to 5% O2 . Despite their similar total cell numbers, higher rates of
      inner cell mass (ICM) cells were observed in blastocysts developed in IVD101
      medium than in those developed in CR1aa, irrespective of O2 tensions. There was
      no significant difference in blastocyst formation, total, ICM and trophectoderm
      (TE) cell numbers between embryos obtained by microdrop and WOW culture systems
      irrespective of the culture media and O2 tensions used. In conclusion, CR1aa
      resulted in higher blastocyst formation rates irrespective of O2 tension, whereas
      IVD101 supported blastocyst formation only under low O2 levels but enhanced the
      proliferation of ICM cells.

PMID- 21087917
TI  - Prevalence of porcine circoviruses in Transylvanian wild boars, detected by real
      time PCR--short communication.
AB  - Porcine circoviruses (PCV) are widespread in domestic pigs worldwide and there is
      growing information about the presence of PCV in other suid species. Based on
      serological studies with sera of wild boars, it was established that PCV1 was
      present in these animals and antibodies specific to PCV2 were also detected in
      wild boars living in captivity or in sylvatic areas, both with or without
      clinical signs of PMWS. Studies including PCV2 genome or antigen detection
      confirmed the previous findings. This is the first report about the presence of
      PCV in Transylvanian wild boar populations. Four hundred and sixty-nine samples
      were collected and grouped according to geographic origin, tested for the
      presence of PCV DNA using a real-time quantitative polymerase chain reaction
      assay, and 13.52% of the animals proved to be positive for one or in three cases
      both of the PCV genotypes. PCV2 was detected in all of the PCV-positive samples.

PMID- 21087918
TI  - Distribution of porcine circovirus 2 cap antigen in the lymphoid tissue of pigs
      affected by postweaning multisystemic wasting syndrome.
AB  - The lymphatic organs of 50 pigs from a total of eight farms located at different
      sites in the epizootiological region of North Backa County were studied to obtain
      data on the prevalence of circoviral infections in Serbia. All of the pigs
      examined had clinical signs suggestive of postweaning multisystemic wasting
      syndrome (PMWS). All pigs underwent necropsy and tissue samples were taken for
      histopathological, immunohistochemical (IHC) and PCR analysis. The presence of
      porcine circovirus 2 (PCV2) was established by PCR analysis in the organs of the
      pigs tested. The most frequent histopathological lesions of lymphoid tissue
      linked with the presence of positive immunostaining for PCV2 Cap antigen
      confirmed the existence of PMWS in all farms tested in North Backa County. Using
      PCR, histopathological and IHC techniques, the presence of PMWS was proved in the
      Republic of Serbia. During necropsy, generalised enlargement of the lymph nodes
      was evident. The most common histopathological finding was lymphocyte depletion
      in the follicular and perifollicular areas of lymph nodes. Infiltration by
      macrophages was also recorded. By IHC analysis, the cytoplasm of macrophages was
      shown to contain a large amount of the ORF2-coded Cap antigen of PCV2. Lymphocyte
      depletion and large numbers of macrophages were recorded in the tonsils, spleen,
      intestinal lymphatic tissue, Peyer's patches and ileocaecal valve. The presence
      of typical granulomatous lesions with multinuclear giant cells (MGCs) was also
      recorded in the lymphatic tissue. Cap antigen was shown to be present in
      macrophages and less often in lymphocytes.

PMID- 21087919
TI  - Biological properties of a naturally attenuated infectious bursal disease virus
      isolated from a backyard chicken flock.
AB  - The biological properties of an infectious bursal disease (IBD) virus isolated
      from bursas collected during an outbreak in a village chicken flock in Macedonia
      are described. The mortality rate was 50%. Two viruses coexisted in the bursas of
      infected chickens (IBDVwt and IBDVtc). The virus termed IBDVtc grows on chicken
      embryo fibroblast (CEF) cells from the first passage. Specific pathogen free
      chickens inoculated with IBDVtc at passage level 4 did not develop any clinical
      signs of disease. Some discrete bleeding on the leg muscles was seen and the
      bursa of Fabricius revealed pathological lesions similar to those caused by
      classical strains. However, the bursa recovered quickly (bursa lesion score 2) by
      14 days post infection (PI). We also found evidence of bursal repopulation by
      means of perinuclear antigen staining. Strong CD3 influx was evident at 4 days
      PI, and at 33 days PI the CD3+ cell finding was comparable to the control. The
      mean antibody titre was 9.2 log 2 at 14 days PI. The amino acid composition of
      VP2 in IBDVwt (222 Ala, 242 Ile, 253 Gln, 256 Ile, 279 Asp, 284 Ala, 294 Ile and
      299 Ser) is described. The same sequence was found in IBDVtc, except for two
      point mutations, at Gln253->His and Ala284->Thr. Such amino acid substitution is
      responsible for partial attenuation and the ability of the strain to replicate in
      cell culture. None of the commercial vaccine viruses has a similar arrangement of
      amino acids in the variable domain of IBDV. This strongly suggests that IBDVtc
      originates from a very virulent strain. To the best of our knowledge, this is the
      first report of a concomitant infection of chickens with highly pathogenic IBDV
      and its mutant counterpart.

PMID- 21087920
TI  - Vaccine production in plant systems--an aid to the control of viral diseases in
      domestic animals: a review.
AB  - Plants have been identified as promising expression systems for the commercial
      production of vaccines because of the possibility of introducing exogenous genes
      into them, which permits the development of a new generation of biological
      products called edible vaccines. The advantages of oral vaccines of this new type
      are that they induce mucosal, humoral, cellular and protective immunity, they are
      cheaper, easier to store, distribute and administer, they do not require cold
      chain management, and some species can be stored for long periods of time without
      any spoilage and may be administered as purified proteins. Owing to these
      benefits, plant-produced vaccines represent a valuable option for animal health.
      The aim of this paper is to present a review of plant-produced vaccines against
      viruses affecting domestic animals. Some aspects of the feasibility of their use
      and the immune response elicited by such vaccines are also discussed, as the
      balance between tolerance and immunogenicity is a major concern for the use of
      plant-based vaccines.

PMID- 21087921
TI  - Abstracts of the 5th International Meeting of the Onassis Cardiac Surgery Center 
      16-18 September 2010, Athens, Greece.

PMID- 21087922
TI  - Engagement and retention: measuring breadth and depth of participant use of an
      online intervention.
AB  - BACKGROUND: The Internet provides us with tools (user metrics or paradata) to
      evaluate how users interact with online interventions. Analysis of these paradata
      can lead to design improvements. OBJECTIVE: The objective was to explore the
      qualities of online participant engagement in an online intervention. We analyzed
      the paradata in a randomized controlled trial of alternative versions of an
      online intervention designed to promote consumption of fruit and vegetables.
      METHODS: Volunteers were randomized to 1 of 3 study arms involving several online
      sessions. We created 2 indirect measures of breadth and depth to measure
      different dimensions and dynamics of program engagement based on factor analysis
      of paradata measures of Web pages visited and time spent online with the
      intervention materials. Multiple regression was used to assess influence of
      engagement on retention and change in dietary intake. RESULTS: Baseline surveys
      were completed by 2513 enrolled participants. Of these, 86.3% (n = 2168)
      completed the follow-up surveys at 3 months, 79.6% (n = 2027) at 6 months, and
      79.4% (n = 1995) at 12 months. The 2 tailored intervention arms exhibited
      significantly more engagement than the untailored arm (P < .01). Breadth and
      depth measures of engagement were significantly associated with completion of
      follow-up surveys (odds ratios [OR] = 4.11 and 2.12, respectively, both P values
      < .001). The breadth measure of engagement was also significantly positively
      associated with a key study outcome, the mean increase in fruit and vegetable
      consumption (P < .001). CONCLUSIONS: By exploring participants' exposures to
      online interventions, paradata are valuable in explaining the effects of
      tailoring in increasing participant engagement in the intervention. Controlling
      for intervention arm, greater engagement is also associated with retention of
      participants and positive change in a key outcome of the intervention, dietary
      change. This paper demonstrates the utility of paradata capture and analysis for
      evaluating online health interventions. TRIAL REGISTRATION: NCT00169312;
      http://clinicaltrials.gov/ct2/show/NCT00169312 (Archived by WebCite at
      http://www.webcitation.org/5u8sSr0Ty).

PMID- 21087923
TI  - Patients with traumatic brain injury are at high risk of developing chronic sleep
      wake disturbances.

PMID- 21087924
TI  - Do twin studies still have anything to teach us about the genetics of amyotrophic
      lateral sclerosis?

PMID- 21087925
TI  - Insights into the mechanism of type I dehydroquinate dehydratases from structures
      of reaction intermediates.
AB  - The biosynthetic shikimate pathway consists of seven enzymes that catalyze
      sequential reactions to generate chorismate, a critical branch point in the
      synthesis of the aromatic amino acids. The third enzyme in the pathway,
      dehydroquinate dehydratase (DHQD), catalyzes the dehydration of 3-dehydroquinate
      to 3-dehydroshikimate. We present three crystal structures of the type I DHQD
      from the intestinal pathogens Clostridium difficile and Salmonella enterica.
      Structures of the enzyme with substrate and covalent pre- and post-dehydration
      reaction intermediates provide snapshots of successive steps along the type I
      DHQD-catalyzed reaction coordinate. These structures reveal that the position of
      the substrate within the active site does not appreciably change upon Schiff base
      formation. The intermediate state structures reveal a reaction state-dependent
      behavior of His-143 in which the residue adopts a conformation proximal to the
      site of catalytic dehydration only when the leaving group is present. We
      speculate that His-143 is likely to assume differing catalytic roles in each of
      its observed conformations. One conformation of His-143 positions the residue for
      the formation/hydrolysis of the covalent Schiff base intermediates, whereas the
      other conformation positions the residue for a role in the catalytic dehydration
      event. The fact that the shikimate pathway is absent from humans makes the
      enzymes of the pathway potential targets for the development of non-toxic
      antimicrobials. The structures and mechanistic insight presented here may inform
      the design of type I DHQD enzyme inhibitors.

PMID- 21087926
TI  - Epigenomic reorganization of the clustered Hox genes in embryonic stem cells
      induced by retinoic acid.
AB  - Retinoic acid (RA) regulates clustered Hox gene expression during embryogenesis
      and is required to establish the anterior-posterior body plan. Using mutant
      embryonic stem cell lines deficient in the RA receptor gamma (RARgamma) or Hoxa1
      3'-RA-responsive element, we studied the kinetics of transcriptional and
      epigenomic patterning responses to RA. RARgamma is essential for RA-induced Hox
      transcriptional activation, and deletion of its binding site in the Hoxa1
      enhancer attenuates transcriptional and epigenomic activation of both Hoxa and
      Hoxb gene clusters. The kinetics of epigenomic reorganization demonstrate that
      complete erasure of the polycomb repressive mark H3K27me3 is not necessary to
      initiate Hox transcription. RARgamma is not required to establish the bivalent
      character of Hox clusters, but RA/RARgamma signaling is necessary to erase
      H3K27me3 from activated Hox genes during embryonic stem cell differentiation.
      Highly coordinated, long range epigenetic Hox cluster reorganization is closely
      linked to transcriptional activation and is triggered by RARgamma located at the
      Hoxa1 3'-RA-responsive element.

PMID- 21087927
TI  - Paired immunoglobulin-like receptor B knockout does not enhance axonal
      regeneration or locomotor recovery after spinal cord injury.
AB  - Myelin components that inhibit axonal regeneration are believed to contribute
      significantly to the lack of axonal regeneration noted in the adult central
      nervous system. Three proteins found in myelin, Nogo, myelin-associated
      glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth
      in vitro. All of these proteins interact with the same receptors, namely, the
      Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per
      previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR
      knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration
      in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using
      the Basso mouse scale, footprint test, inclined plane test, and beam walking
      test, did not differ between the PIR-B-knock-out and wild-type mice after dorsal
      hemisection of the spinal cord. Further, tracing of the CST fibers after injury
      did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B
      knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B
      knock-out mice did not enhance the regenerative response. These results indicate
      that PIR-B knock-out is not sufficient to induce extensive axonal regeneration
      after spinal cord injury.

PMID- 21087928
TI  - HoxA10 regulates transcription of the gene encoding transforming growth factor
      beta2 (TGFbeta2) in myeloid cells.
AB  - HoxA10 is a homeodomain transcription factor that is maximally expressed in
      myeloid progenitor cells. HoxA10 is overexpressed in a poor prognosis subset of
      human acute myeloid leukemia (AML) and in vivo overexpression of HoxA10 in murine
      bone marrow induces myeloid leukemia. HoxA10 contributes to myeloid progenitor
      expansion and differentiation block, but few target genes have been identified
      that explain the influence of HoxA10 on these processes. The current study
      identifies the gene encoding transforming growth factor beta2 (TGFbeta2) as a
      HoxA10 target gene. We found that HoxA10 activated TGFbeta2 transcription by
      interacting with tandem cis elements in the promoter. We also determined that
      HoxA10 overexpression in myeloid progenitor cells increased Tgfbeta2 production
      by the cells. Tgfbeta2 stimulates proliferation of hematopoietic stem and
      progenitor cells. Therefore, these studies identified autocrine stimulation of
      myeloid progenitors by Tgfbeta2 as one mechanism by which HoxA10 expands this
      population. Because HoxA proteins had not been previously known to influence
      expression of pro-proliferative cytokines, this has implications for
      understanding molecular mechanisms involved in progenitor expansion and the
      pathobiology of AML.

PMID- 21087929
TI  - The intra-S phase checkpoint protein Tof1 collaborates with the helicase Rrm3 and
      the F-box protein Dia2 to maintain genome stability in Saccharomyces cerevisiae.
AB  - The intra-S phase checkpoint protein complex Tof1/Csm3 of Saccharomyces
      cerevisiae antagonizes Rrm3 helicase to modulate replication fork arrest not only
      at the replication termini of rDNA but also at strong nonhistone protein binding
      sites throughout the genome. We investigated whether these checkpoint proteins
      acted either antagonistically or synergistically with Rrm3 in mediating other
      important functions such as maintenance of genome stability. High retromobility
      of a normally quiescent retrovirus-like transposable element Ty1 of S. cerevisiae
      is a form of genome instability, because the transposition events induce
      mutations. We measured the transposition of Ty1 in various genetic backgrounds
      and discovered that Tof1 suppressed excessive retromobility in collaboration with
      either Rrm3 or the F-box protein Dia2. Although both Rrm3 and Dia2 are believed
      to facilitate fork movement, fork stalling at DNA-protein complexes did not
      appear to be a major contributor to enhancement of retromobility. Absence of the
      aforementioned proteins either individually or in pair-wise combinations caused
      karyotype changes as revealed by the altered migrations of the individual
      chromosomes in pulsed field gels. The mobility changes were RNase H-resistant and
      therefore, unlikely to have been caused by extensive R loop formation. These
      mutations also resulted in alterations of telomere lengths. However, the latter
      changes could not fully account for the magnitude of the observed karyotypic
      alterations. We conclude that unlike other checkpoint proteins that are known to
      be required for elevated retromobility, Tof1 suppressed high frequency
      retrotransposition and maintained karyotype stability in collaboration with the
      aforementioned proteins.

PMID- 21087930
TI  - Role of RecJ-like protein with 5'-3' exonuclease activity in
      oligo(deoxy)nucleotide degradation.
AB  - RecJ-like proteins belonging to the DHH family have been proposed to function as
      oligoribonucleases and 3'-phosphoadenosine 5'-phosphate (pAp) phosphatases in
      bacteria and archaea, which do not have Orn (oligoribonuclease) and CysQ (pAp
      phosphatase) homologs. In this study, we analyzed the biochemical and
      physiological characterization of the RecJ-like protein TTHA0118 from Thermus
      thermophilus HB8. TTHA0118 had high enzymatic activity as an
      oligodeoxyribonucleotide- and oligoribonucleotide-specific exonuclease and as pAp
      phosphatase. The polarity of degradation was 5' to 3', in contrast to previous
      reports about Bacillus subtilis NrnA, a RecJ-like protein. TTHA0118
      preferentially hydrolyzed short oligodeoxyribonucleotides and
      oligoribonucleotides, whereas the RecJ exonuclease from T. thermophilus HB8
      showed no such length dependence on oligodeoxyribonucleotide substrates. An
      insertion mutation of the ttha0118 gene led to growth reduction in minimum
      essential medium. Added 5'-mononucleotides, nucleosides, and cysteine increased
      growth of the ttha0118 mutant in minimum essential medium. The RecJ-like protein
      Mpn140 from Mycoplasma pneumoniae M129, which cannot synthesize nucleic acid
      precursors de novo, showed similar biochemical features to TTHA0118. Furthermore,
      B. subtilis NrnA also hydrolyzed oligo(deoxy)ribonucleotides in a 5'-3'
      direction. These results suggested that these RecJ-like proteins act in recycling
      short oligonucleotides to mononucleotides and in controlling pAp concentrations
      in vivo.

PMID- 21087931
TI  - A p27(kip1)-binding protein, p27RF-Rho, promotes cancer metastasis via activation
      of RhoA and RhoC.
AB  - Rho family proteins regulate multiple cellular functions including motility and
      invasion through regulation of the actin cytoskeleton and gene expression.
      Activation of Rho proteins is controlled precisely by multiple regulators in a
      spatiotemporal manner. RhoA and/or RhoC are key players that regulate the
      metastatic activity of malignant tumor cells, and it is therefore of particular
      interest to understand how activation of these Rho proteins is controlled. We
      recently identified an upstream regulator of RhoA activation, p27RF-Rho
      (p27(kip1) releasing factor from RhoA) that acts by freeing RhoA from inhibition
      by p27(kip1). p27(kip1) is a cell cycle regulator when it is localized to the
      nucleus, but it binds RhoA and inhibits activation of the latter when it is
      localized to the cytoplasm. Here, we show that a metastatic variant of mouse
      melanoma B16 cells (F10) exhibits greater expression of p27RF-Rho, RhoA, and RhoC
      than the nonmetastatic parental cells (F0). Injection of F10 cells into mouse
      tail vein resulted in the formation of metastatic lung colonies, whereas prior
      knockdown of expression of either one of the three proteins using specific shRNA
      sequences decreased metastasis markedly. p27RF-Rho regulated the activation of
      RhoA and RhoC and thereby modulated cellular adhesion and motility, in addition
      to pericellular proteolysis. The Rho activities enhanced by p27RF-Rho had a
      marked effect upon efficiency of lodging of F10 cells in the lung, which
      represents an early step of metastasis. p27RF-Rho also regulated metastasis of
      human melanoma and fibrosarcoma cells. Thus, p27RF-Rho is a key upstream
      regulator of RhoA and RhoC that controls spreading of tumor cells.

PMID- 21087932
TI  - Prolylcarboxypeptidase regulates proliferation, autophagy, and resistance to 4
      hydroxytamoxifen-induced cytotoxicity in estrogen receptor-positive breast cancer
      cells.
AB  - Endocrine therapy with tamoxifen (TAM) significantly improves outcomes for
      patients with estrogen receptor-positive breast cancer. However, intrinsic (de
      novo) or acquired resistance to TAM occurs in a significant proportion of treated
      patients. To identify genes involved in resistance to TAM, we introduced full
      length cDNA expression library into estrogen receptor-positive MCF7 cells and
      exposed them to a cytotoxic dose of 4-hydroxytamoxifen (4OHTAM). Four different
      library inserts were isolated from surviving clones. Re-introduction of the genes
      individually into naive MCF7 cells made them resistant to 4OHTAM. Cells
      overexpressing these genes had an increase in acidic autophagic vacuoles induced
      by 4OHTAM, suggesting their role in autophagy. One of them,
      prolylcarboxypeptidase (PRCP), was investigated further. Overexpression of PRCP
      increased cell proliferation, boosted several established markers of autophagy,
      including expression of LC3-2, sequestration of monodansylcadaverine, and
      proteolysis of BSA in an ER-alpha dependent manner, and increased resistance to
      4OHTAM. Conversely, knockdown of endogenous PRCP in MCF7 cells increased cell
      sensitivity to 4OHTAM and at the same time decreased cell proliferation and
      expression of LC3-2, sequestration of monodansylcadaverine, and proteolysis of
      BSA. Inhibition of enzymatic activity of PRCP enhanced 4OHTAM-induced
      cytotoxicity in MCF7 cells. Cells with acquired resistance to 4OHTAM exhibited
      increased PRCP activity, although inhibition of PRCP prevented development of
      4OHTAM resistance in parental MCF7 cells and restored response to 4OHTAM in MCF7
      cells with acquired resistance to 4OHTAM. Thus, we have for the first time
      identified PRCP as a resistance factor for 4OHTAM resistance in estrogen receptor
      positive breast cancer cells.

PMID- 21087934
TI  - Degeneration of the mid-cingulate cortex in amyotrophic lateral sclerosis
      detected in vivo with MR spectroscopy.
AB  - BACKGROUND AND PURPOSE: Various lines of evidence implicate cerebral involvement
      beyond the motor cortex in ALS, including the cingulate gyrus and the thalamus.
      The purpose of this study was to assess neurodegeneration in these regions in
      vivo by using MRSI. MATERIALS AND METHODS: Fourteen patients with ALS and 14
      healthy controls underwent MRSI by using a coronal acquisition scheme. The
      NAA/Cho ratio was quantified in the MCC, thalamus, and motor cortex (PCG).
      RESULTS: NAA/Cho was reduced in the MCC in patients with ALS compared with the
      controls (P = .0004). There was no difference in NAA/Cho in the thalamus (P =
      .59). We also found a strong correlation of NAA/Cho among the PCG, MCC, and the
      thalamus in controls, which was absent in patients with ALS. CONCLUSIONS:
      Neurodegeneration beyond the motor cortex is present in the MCC in ALS. The
      significant correlation of NAA/Cho among the PCG, MCC, and the thalamus in
      healthy subjects likely reflects the neuronal connectivity among these regions.
      The loss of these relationships in patients with ALS suggests that such
      connectivity is not responsible for the pattern of degeneration in these regions.

PMID- 21087933
TI  - Low cholesterol triggers membrane microdomain-dependent CD44 shedding and
      suppresses tumor cell migration.
AB  - CD44 is a cell surface adhesion molecule for hyaluronan and is implicated in
      tumor invasion and metastasis. Proteolytic cleavage of CD44 plays a critical role
      in the migration of tumor cells and is regulated by factors present in the tumor
      microenvironment, such as hyaluronan oligosaccharides and epidermal growth
      factor. However, molecular mechanisms underlying the proteolytic cleavage on
      membranes remain poorly understood. In this study, we demonstrated that
      cholesterol depletion with methyl-beta-cyclodextrin, which disintegrates membrane
      lipid rafts, enhances CD44 shedding mediated by a disintegrin and
      metalloproteinase 10 (ADAM10) and that cholesterol depletion disorders CD44
      localization to the lipid raft. We also evaluated the effect of long term
      cholesterol reduction using a statin agent and demonstrated that statin enhances
      CD44 shedding and suppresses tumor cell migration on a hyaluronan-coated
      substrate. Our results indicate that membrane lipid organization regulates CD44
      shedding and propose a possible molecular mechanism by which cholesterol
      reduction might be effective for preventing and treating the progression of
      malignant tumors.

PMID- 21087935
TI  - Quantitative diffusion-weighted and dynamic susceptibility-weighted contrast
      enhanced perfusion MR imaging analysis of T2 hypointense lesion components in
      pediatric diffuse intrinsic pontine glioma.
AB  - BACKGROUND AND PURPOSE: Focal anaplasia characterized by T2 hypointensity, signal
      intensity enhancement on postcontrast T1-weighted MR imaging and restricted water
      diffusion has been reported in a patient with juvenile pilocytic astrocytoma. We
      identified T2(HOF) with these MR imaging characteristics in children with DIPG
      and hypothesized that these represent areas of focal anaplasia; and may,
      therefore, have increased perfusion properties and should be characterized by
      increased perfusion. Thus, we used DSC to investigate our hypothesis. MATERIALS
      AND METHODS: We retrospectively reviewed the baseline MR imaging scans of 86
      patients (49 girls, 37 boys; median age, 6.1 years; range, 1.1-17.6 years)
      treated for DIPG at our hospital (2004-2009). T2(HOF) with the described MR
      imaging characteristics was identified in 10 patients. We used a region of
      interest-based approach to compare the ADC, FA, rCBV, rCBF, and rMTT of T2(HOF)
      with those of the typical T2(HRT). RESULTS: The ADC of T2(HOF) with the specified
      MR imaging characteristics was significantly lower than that of T2(HRT) (range,
      0.71-1.95 MUm(2)/ms versus 1.36-2.13 MUm(2)/ms; P < .01); and the FA (range, 0.12
      0.34 versus 0.07-0.24; P = .03) and rCBV (range, 0.4-2.62 versus 0.23-1.57; P =
      .01) values of T2(HOF)s were significantly higher. CONCLUSIONS: Our data suggest
      that T2(HOF) in DIPG may represent areas of focal anaplasia and underline the
      importance of regional, rather than global, tumor-field analysis. T2(HOF) may be
      the ideal target when stereotactic biopsy of tumors that present with an
      inhomogeneous T2 signal intensity is considered.

PMID- 21087936
TI  - Anomalous extraocular muscles with strabismus.
AB  - SUMMARY: An 8-month-old boy with Gorlin syndrome presented with a large right
      face turn and constant exotropia of the left eye. Eight-millimeter recession of
      the left lateral rectus muscle was performed at 23 months of age without complete
      postoperative improvement. Orbital imaging revealed bilateral anomalous
      extraocular muscles inferolateral to the optic nerves. Surgical resection of the
      tissue confirmed the accessory musculature with postoperative correction of the
      strabismus. To our knowledge, this appears to be the first reported case in the
      radiologic literature.

PMID- 21087937
TI  - Efficacy and safety of ethanol ablation for thyroglossal duct cysts.
AB  - BACKGROUND AND PURPOSE: TGDC is a common congenital neck lesion, which has been
      treated by surgery. Although surgery is curative, it has drawbacks such as scars
      and surgical morbidity. Therefore, we applied EA as an alternative treatment
      technique. The purpose of this study was the evaluation of the efficacy and
      safety of EA for TGDC. MATERIALS AND METHODS: Between May 2005 and July 2008, we
      performed EA in 11 patients with TGDC who refused surgery. All patients were
      confirmed as having benign lesions before treatment. US-guided aspiration of the
      cystic fluid was followed by injection of absolute ethanol (99%). The injected
      volume of ethanol was 50%-80% of the volume of fluid aspirated. We evaluated the
      therapeutic outcome, including volume reduction of the TGDC, improvement of
      cosmetic problems and symptoms, and complications. RESULTS: The initial volume of
      the cysts ranged from 0.67 to 29.39 mL (mean, 6.0 mL). The procedure was
      performed in 1-3 sessions (mean, 1.4 sessions). Follow-up US was performed in 10
      patients from 3 to 29 months (mean, 13.6 months). The mean volume of the cyst was
      6.0 +/- 8.4 mL, and volume reduction was 43.9%-100% (mean, 81.3%, P = .005) at
      last follow-up. Therapeutic success (volume reduction of >50%) was observed in 8
      patients (8/10, 80%). Significant improvement of symptom- (P = .005) and cosmetic
      grading scores (P = .003) was observed at last follow-up. No significant
      complications were observed during the procedure or follow-up periods.
      CONCLUSIONS: EA seems to be an effective and safe treatment method for TGDC.

PMID- 21087938
TI  - Optimization and initial experience of a multisection balanced steady-state free
      precession cine sequence for the assessment of fetal behavior in utero.
AB  - BACKGROUND AND PURPOSE: The assessment of motor function is an essential
      component of neurologic examinations, which imaging studies have extended to the
      fetus. US assessment is hampered by a limited FOV, whereas MR imaging has the
      potential to be an alternative. Our objectives were to optimize a cine MR imaging
      sequence for capturing fetal movements and to perform a pilot analysis of the
      relationship between the frequency of movements and uterine spatial constrictions
      in healthy fetuses. MATERIALS AND METHODS: Initially, a bSSFP cine sequence was
      selected for optimization, and various compromises were explored in all
      acquisition parameters to achieve an effective balance between anatomic coverage
      of the fetus and the temporal resolution of cine data, with the aim of maximizing
      both. Subsequently, cross-sectional qualitative and quantitative analyses of
      fetal movements were performed prospectively by using a cohort of 37 healthy
      fetuses (median GA, 29 weeks; range, 20-37 weeks) with the optimized cine
      protocol. Two smaller subgroups were selected for representative sampling of
      overall behavior patterns by using cine data of longer duration and for
      volumetric quantification of free intrauterine space. RESULTS: The optimized cine
      sequence, with TR/TE of 3.21/1.59 ms, coupled with parallel imaging and partial
      Fourier imaging, resulted in a section-acquisition time of 0.303 seconds.
      Anatomic coverage was enhanced by using a combination of thick sagittal sections
      (30-40 mm) and multisection acquisitions to display movements in all fetal limbs,
      head, and trunk simultaneously. All expected motor patterns were observed
      throughout this gestational period, and a significant decreasing trend in overall
      movement frequency with age was demonstrated (r = -0.514, P = .0011). Also a
      significant negative correlation was found between overall movement frequency and
      the total intrauterine free space (r = -0.703, P = .0001). Furthermore, a
      significant decrease in the frequency of leg movements was shown in fetuses older
      then 30 weeks' GA compared with those younger than that (P = .015). CONCLUSIONS:
      Cine MR imaging is effective for observing fetal movements from midgestation with
      near full-body coverage. Also, reductions in free space with increasing GA appear
      to be a factor in the gradual reductions in overall levels of fetal activity as
      well as in restrictions in movement within specific regions of the fetal anatomy.

PMID- 21087939
TI  - A sparse intraoperative data-driven biomechanical model to compensate for brain
      shift during neuronavigation.
AB  - BACKGROUND AND PURPOSE: Intraoperative brain deformation is an important factor
      compromising the accuracy of image-guided neurosurgery. The purpose of this study
      was to elucidate the role of a model-updated image in the compensation of
      intraoperative brain shift. MATERIALS AND METHODS: An FE linear elastic model was
      built and evaluated in 11 patients with craniotomies. To build this model, we
      provided a novel model-guided segmentation algorithm. After craniotomy, the
      sparse intraoperative data (the deformed cortical surface) were tracked by a 3D
      LRS. The surface deformation, calculated by an extended RPM algorithm, was
      applied on the FE model as a boundary condition to estimate the entire brain
      shift. The compensation accuracy of this model was validated by the real-time
      image data of brain deformation acquired by intraoperative MR imaging. RESULTS:
      The prediction error of this model ranged from 1.29 to 1.91 mm (mean, 1.62 +/-
      0.22 mm), and the compensation accuracy ranged from 62.8% to 81.4% (mean, 69.2 +/
      5.3%). The compensation accuracy on the displacement of subcortical structures
      was higher than that of deep structures (71.3 +/- 6.1%:66.8 +/- 5.0%, P < .01).
      In addition, the compensation accuracy in the group with a horizontal bone window
      was higher than that in the group with a nonhorizontal bone window (72.0 +/-
      5.3%:65.7 +/- 2.9%, P < .05). CONCLUSIONS: Combined with our novel model-guided
      segmentation and extended RPM algorithms, this sparse data-driven biomechanical
      model is expected to be a reliable, efficient, and convenient approach for
      compensation of intraoperative brain shift in image-guided surgery.

PMID- 21087940
TI  - Direct thrombus retrieval using the reperfusion catheter of the penumbra system:
      forced-suction thrombectomy in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Although the PS has been the most promising mechanical
      thrombectomy device in terms of recanalization rates, even the PS cannot
      recanalize all cases of occlusion. Under such circumstances, we simply modified
      the PS, identified certain advantages, and applied this modification as a primary
      technique for recanalization. Here we describe and discuss the technical details
      and results of our preliminary experience. MATERIALS AND METHODS: This study
      included 22 consecutive patients with acute ischemic stroke secondary to large
      artery occlusion who underwent modified thrombectomy by using the PS for
      recanalization. Direct wedging between the tip of the reperfusion catheter and
      the proximal part of the clot followed by forceful suction by using a 20- or 50
      mL syringe is a unique feature of this technique. What is distinctive is that
      this does not require use of a separator or aspiration pump. RESULTS: All treated
      vessels (100%) were successfully recanalized. A TICI scale of 2b or 3 was
      achieved in 81.9% of patients. A 3-month favorable functional outcome (mRS score,
      0-2) was achieved in 45.5% of patients. The only procedural complication was a
      transient dissection of the proximal ICA, which developed while advancing the
      guide catheter. CONCLUSIONS: Forced-suction thrombectomy is a simple modification
      of the PS. On the basis of our data, this technique allows safe and effective
      revascularization in acute large-vessel occlusion. Thus, for achieving the best
      outcome, the modified PS technique is proposed as a viable option for acute
      stroke management, either by itself or in conjunction with other devices or
      drugs.

PMID- 21087941
TI  - MR imaging of partially thrombosed cerebral aneurysms: characteristics and
      evolution.
AB  - BACKGROUND AND PURPOSE: A comprehensive evaluation of aneurysmal morphometry
      requires appreciation of both the vascular lumen and the intraluminal thrombus.
      MR imaging methods can both evaluate the lumen and directly image the vessel
      wall. We investigated the ability of T1-weighted, T2-weighted, and steady-state
      MR imaging techniques to delineate thrombus morphology and reveal changes with
      time. MATERIALS AND METHODS: Nine patients with fusiform basilar or intracranial
      vertebral artery aneurysms that contained intraluminal thrombus were studied with
      MR imaging. All patients underwent at least 2 imaging sessions, which were
      separated by 4-22 months. Analysis of signal intensity to determine the mean
      signal intensity from thrombus, blood, CSF, and brain in matched regions was
      performed. Aneurysm maximal diameter and cross-sectional area were determined
      with and without thrombus. RESULTS: Thrombus was identified on all image
      sequences, and its general appearance was consistent between imaging sessions.
      Thrombus produced the highest and most consistent signal intensities with T1
      weighted and steady-state techniques, though the latter showed superior contrast
      between luminal blood and thrombus. Heterogeneity within clot was evident in 4/9
      of patients, with peripheral hyperintensity being a common feature. CONCLUSIONS:
      Steady-state imaging was found to be superior to T1- and T2-weighted imaging for
      delineating and characterizing intraluminal thrombus within aneurysms. The
      imaging characteristics of intraluminal thrombus proved to be very consistent for
      long periods. Assessment of overall aneurysm size, including thrombosed portions,
      permits more accurate evaluation of aneurysm growth and concomitantly may permit
      more informed clinical decision-making with regard to the timing and need for
      aneurysm treatment.

PMID- 21087942
TI  - Acute hyperammonemic encephalopathy in adults: imaging findings.
AB  - BACKGROUND AND PURPOSE: Acute hyperammonemic encephalopathy has significant
      morbidity and mortality unless promptly treated. We describe the MR imaging
      findings of acute hyperammonemic encephalopathy, which are not well-recognized in
      adult patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical
      and imaging data and outcome of consecutive patients with documented
      hyperammonemic encephalopathy seen at our institution. All patients underwent
      cranial MR imaging at 1.5T. RESULTS: Four patients (2 women; mean age, 42 +/- 13
      years; range, 24-55 years) were included. Causes included acute fulminant hepatic
      failure, and sepsis with a background of chronic hepatic failure and post-heart
      lung transplantation with various systemic complications. Plasma ammonia levels
      ranged from 55 to 168 MUmol/L. Bilateral symmetric signal-intensity
      abnormalities, often with associated restricted diffusion involving the insular
      cortex and cingulate gyrus, were seen in all cases, with additional cortical
      involvement commonly seen elsewhere but much more variable and asymmetric.
      Involvement of the subcortical white matter was seen in 1 patient only. Another
      patient showed involvement of the basal ganglia, thalami, and midbrain. Two
      patients died (1 with fulminant cerebral edema), and 2 patients survived (1
      neurologically intact and the other with significant intellectual impairment).
      CONCLUSIONS: The striking common imaging finding was symmetric involvement of the
      cingulate gyrus and insular cortex in all patients, with more variable and
      asymmetric additional cortical involvement. These specific imaging features
      should alert the radiologist to the possibility of acute hyperammonemic
      encephalopathy.

PMID- 21087943
TI  - Low Incidence of neurologic complications during thoracic epidurals: anatomic
      explanation.

PMID- 21087944
TI  - Statistical properties of the branch-site test of positive selection.
AB  - The branch-site test is a likelihood ratio test to detect positive selection
      along prespecified lineages on a phylogeny that affects only a subset of codons
      in a protein-coding gene, with positive selection indicated by accelerated
      nonsynonymous substitutions (with omega = d(N)/d(S) > 1). This test may have more
      power than earlier methods, which average nucleotide substitution rates over
      sites in the protein and/or over branches on the tree. However, a few recent
      studies questioned the statistical basis of the test and claimed that the test
      generated too many false positives. In this paper, we examine the null
      distribution of the test and conduct a computer simulation to examine the false
      positive rate and the power of the test. The results suggest that the asymptotic
      theory is reliable for typical data sets, and indeed in our simulations, the
      large-sample null distribution was reliable with as few as 20-50 codons in the
      alignment. We examined the impact of sequence length, the strength of positive
      selection, and the proportion of sites under positive selection on the power of
      the branch-site test. We found that the test was far more powerful in detecting
      episodic positive selection than branch-based tests, which average substitution
      rates over all codons in the gene and thus miss the signal when most codons are
      under strong selective constraint. Recent claims of statistical problems with the
      branch-site test are due to misinterpretations of simulation results. Our
      results, as well as previous simulation studies that have demonstrated the
      robustness of the test, suggest that the branch-site test may be a useful tool
      for detecting episodic positive selection and for generating biological
      hypotheses for mutation studies and functional analyses. The test is sensitive to
      sequence and alignment errors and caution should be exercised concerning its use
      when data quality is in doubt.

PMID- 21087946
TI  - Probabilistic classifiers with high-dimensional data.
AB  - For medical classification problems, it is often desirable to have a probability
      associated with each class. Probabilistic classifiers have received relatively
      little attention for small n large p classification problems despite of their
      importance in medical decision making. In this paper, we introduce 2 criteria for
      assessment of probabilistic classifiers: well-calibratedness and refinement and
      develop corresponding evaluation measures. We evaluated several published high
      dimensional probabilistic classifiers and developed 2 extensions of the Bayesian
      compound covariate classifier. Based on simulation studies and analysis of gene
      expression microarray data, we found that proper probabilistic classification is
      more difficult than deterministic classification. It is important to ensure that
      a probabilistic classifier is well calibrated or at least not "anticonservative"
      using the methods developed here. We provide this evaluation for several
      probabilistic classifiers and also evaluate their refinement as a function of
      sample size under weak and strong signal conditions. We also present a cross
      validation method for evaluating the calibration and refinement of any
      probabilistic classifier on any data set.

PMID- 21087945
TI  - Unexpected repertoire of metazoan transcription factors in the unicellular
      holozoan Capsaspora owczarzaki.
AB  - How animals (metazoans) originated from their single-celled ancestors remains a
      major question in biology. As transcriptional regulation is crucial to animal
      development, deciphering the early evolution of associated transcription factors
      (TFs) is critical to understanding metazoan origins. In this study, we uncovered
      the repertoire of 17 metazoan TFs in the amoeboid holozoan Capsaspora owczarzaki,
      a representative of a unicellular lineage that is closely related to
      choanoflagellates and metazoans. Phylogenetic and comparative genomic analyses
      with the broadest possible taxonomic sampling allowed us to formulate new
      hypotheses regarding the origin and evolution of developmental metazoan TFs. We
      show that the complexity of the TF repertoire in C. owczarzaki is strikingly
      high, pushing back further the origin of some TFs formerly thought to be metazoan
      specific, such as T-box or Runx. Nonetheless, TF families whose beginnings
      antedate the origin of the animal kingdom, such as homeodomain or basic helix
      loop-helix, underwent significant expansion and diversification along metazoan
      and eumetazoan stems.

PMID- 21087947
TI  - Electroconvulsive therapy in palliative care.
AB  - Electroconvulsive therapy (ECT) is a highly effective psychiatric treatment for
      states of depression, mania, psychosis, or behavioral agitation in dementia. As
      it does involve intravenous access, general anesthesia, and significant side
      effects, it may be viewed as too ''invasive'' for patients on palliative care
      measures. However, we describe several patients treated on our busy ECT service
      at a tertiary hospital, who were receiving palliative care who, on balance, were
      felt to have better quality of life with continued use of ECT. We conclude that
      ECT should not be automatically discarded in patients receiving palliative care
      and offer some guidelines for its use in this population.

PMID- 21087948
TI  - Supporting the volunteer career of male hospice-palliative care volunteers.
AB  - We invited men to discuss their volunteer careers with hospice-palliative care
      (HPC) to better understand how to recruit and train, retain and support, and then
      successfully end their volunteer experience. Nine male current or former HPC
      volunteers participated in face-to-face interviews which were transcribed and
      analyzed. The men described a complex interplay of individual characteristics
      with the unique roles available to HPC volunteers. The men's recruitment
      experiences coalesced around both individually based and organizationally based
      themes. Results pertaining to retention revealed the interchange between their
      personalities, the perks and pitfalls of the unique experiences of an HPC
      volunteer, and the value of the organization's support for these volunteers. Our
      interpretation of these experiences can help HPC organizations enhance their
      recruitment, retention, and support of male volunteers.

PMID- 21087950
TI  - Editorial: Bioinformatics education in the 21st century.

PMID- 21087949
TI  - Ranking prognosis markers in cancer genomic studies.
AB  - In cancer research, high-throughput genomic studies have been extensively
      conducted, searching for markers associated with cancer diagnosis, prognosis and
      variation in response to treatment. In this article, we analyze cancer prognosis
      studies and investigate ranking markers based on their marginal prognosis power.
      To avoid ambiguity, we focus on microarray gene expression studies where genes
      are the markers, but note that the methodology and results are applicable to
      other high-throughput studies. The objectives of this study are 2-fold. First, we
      investigate ranking markers under three commonly adopted semiparametric models,
      namely the Cox, accelerated failure time and additive risk models. Data analysis
      shows that the ranking may vary significantly under different models. Second, we
      describe a nonparametric concordance measure, which has roots in the time
      dependent ROC (receiver operating characteristic) framework and relies on much
      weaker assumptions than the semiparametric models. In simulation, it is shown
      that ranking using the concordance measure is not sensitive to model
      specification whereas ranking under the semiparametric models is. In data
      analysis, the concordance measure generates rankings significantly different from
      those under the semiparametric models.

PMID- 21087951
TI  - Venous gas embolism during foam sclerotherapy of saphenous veins despite
      recommended treatment modifications.
AB  - OBJECTIVE: To investigate the effectiveness of methods proposed to prevent venous
      gas embolism during foam sclerotherapy. METHODS: Transthoracic echocardiography
      was performed concurrent with ultrasound-guided sclerotherapy (UGS) of great or
      small saphenous veins. A volume of 2.5 mL of 3% sodium tetradecyl sulphate foam
      was prepared following the Tessari method and injected slowly 5-10 cm away from
      saphenous junctions. The procedure was repeated with modifications including
      using a 5 um filter to generate microfoam, carbon dioxide as the foaming gas, leg
      elevation before or after the injection and immobility post-treatment. RESULTS:
      Bubbles entered the right heart in less than 60 seconds and continued for up to
      50 minutes despite all treatment modifications. None of the patients had a patent
      foramen ovale and none developed any neurological or cardiac symptoms.
      CONCLUSION: Bubble emboli entered the heart during foam UGS of saphenous veins
      despite all treatment modifications and low volumes of foam used.

PMID- 21087952
TI  - Cycloplegic and noncycloplegic refractions of Chinese neonatal infants.
AB  - PURPOSE: To examine Chinese neonatal infants with both cycloplegic and
      noncycloplegic retinoscopy and to compare the distribution of refractive errors
      for the two techniques. METHODS: Cycloplegic retinoscopy was performed by two
      experienced pediatric ophthalmologists on 81 neonatal infants randomly selected
      from a group of 185 neonates who had undergone noncycloplegic retinoscopy. All
      infants were between 1 day and 6 days of age and were born without incident at
      full term. RESULTS: The mean cycloplegic spherical equivalent (CSE) was highly
      hyperopic (+3.55 diopters [D] +/- 2.39 D). The mean noncycloplegic spherical
      equivalent (nCSE) was +0.58 D +/- 2.32 D. The high reliability of the refractive
      measurements was demonstrated by high correlations between examiners (CSE: OD, r
      = 0.96; OS, r = 0.97; nCSE: OD, r = 0.94; OS, r = 0.93 OS) and between eyes (CSE:
      examiner 1, r = 0.94; examiner 2, r = 0.95; nCSE: examiner 1, r = 0.95; examiner
      2, r = 0.97). The correlation between CSE and nCSE was much lower (examiner 1:
      OD, r = 0.76; OS, r = 0.73; examiner 2: OD, r = 0.72; OS, r = 0.70). Prevalence
      of astigmatism was very low (1.6% >= 1.0 D). CONCLUSIONS: The level of hyperopia
      was very high in these infants, and the offsetting tonic accommodation
      demonstrated by the difference between CSE and nCSE was much higher than in any
      previous report. Low amounts of infantile hyperopia and high astigmatism are
      associated with future myopia in the West. The Chinese neonates in this study had
      high amounts of hyperopia and little astigmatism, yet they are at high risk to
      become myopic.

PMID- 21087954
TI  - Stereotactic radiosurgery for AMD: a Monte Carlo-based assessment of patient
      specific tissue doses.
AB  - PURPOSE: To define the radiation doses to nontargeted ocular and adnexal tissues
      with Monte-Carlo simulation using a stereotactic low-voltage x-ray irradiation
      system for the treatment of wet age-related macular degeneration. METHODS: Thirty
      two right/left eye models were created from three-dimensional reconstructions of
      1-mm computed tomography images of the head and orbital region. The resultant
      geometric models were voxelized and imported to the MCNPX 2.5.0 radiation
      transport code for Monte Carlo-based simulations of AMD treatment. Clinically,
      treatment is delivered noninvasively by three divergent 100-kVp photon beams
      entering through the sclera and overlapping on the macula cumulating in a
      therapeutic dose. Tissue-averaged doses, localized point doses, and color-coded
      dose contour maps are reported from Monte Carlo simulations of x-ray energy
      deposition for several tissues of interest, including the lens, optic nerve,
      macula, brain, and orbital bone. RESULTS: For all eye models in this study (n =
      32), tissues at risk did not receive tissue-averaged doses over the generally
      accepted thresholds for serious complication, specifically the formation of
      cataracts or radiation-induced optic neuropathy. Dose contour maps are included
      for three patients, each from separate groups defined by coherence to clinically
      realistic treatment setups. Doses to the brain and orbital bone were found to be
      insignificant. CONCLUSIONS: The computational assessment performed indicates that
      a previously established therapeutic dose can be delivered effectively to the
      macula with the scheme described so that the potential for complications to
      nontargeted radiosensitive tissues might be reduced.

PMID- 21087953
TI  - Longitudinal study of cone photoreceptors during retinal degeneration and in
      response to ciliary neurotrophic factor treatment.
AB  - PURPOSE: To study cone photoreceptor structure and function in patients with
      inherited retinal degenerations treated with sustained-release ciliary
      neurotrophic factor (CNTF). METHODS: Two patients with retinitis pigmentosa and
      one with Usher syndrome type 2 who participated in a phase 2 clinical trial
      received CNTF delivered by an encapsulated cell technology implant in one eye and
      sham surgery in the contralateral eye. Patients were followed longitudinally over
      30 to 35 months. Adaptive optics scanning laser ophthalmoscopy (AOSLO) provided
      high-resolution images at baseline and at 3, 6, 12, 18, and 24 months. AOSLO
      measures of cone spacing and density and optical coherence tomography measures of
      retinal thickness were correlated with visual function, including visual acuity
      (VA), visual field sensitivity, and full-field electroretinography (ERG).
      RESULTS: No significant changes in VA, visual field sensitivity, or ERG responses
      were observed in either eye of the three patients over 24 months. Outer retinal
      layers were significantly thicker in CNTF-treated eyes than in sham-treated eyes
      (P < 0.005). Cone spacing increased by 2.9% more per year in sham-treated eyes
      than in CNTF-treated eyes (P < 0.001, linear mixed model), and cone density
      decreased by 9.1%, or 223 cones/degree(2) more per year in sham-treated than in
      CNTF-treated eyes (P = 0.002, linear mixed model). CONCLUSIONS: AOSLO images
      provided a sensitive measure of disease progression and treatment response in
      patients with inherited retinal degenerations. Larger studies of cone structure
      using high-resolution imaging techniques are urgently needed to evaluate the
      effect of CNTF treatment in patients with inherited retinal degenerations.

PMID- 21087955
TI  - Age-related gene response of human corneal endothelium to oxidative stress and
      DNA damage.
AB  - PURPOSE: Nuclear oxidative DNA damage increases with age in human corneal
      endothelial cells (HCECs) and contributes to their decreased proliferative
      capacity. These studies investigated whether HCECs respond to this damage by
      upregulating their expression of oxidative stress and DNA damage-signaling genes
      in an age-dependent manner. METHODS: HCECs were dissected from the corneas of
      young (30 years and younger) and older (50 years and older) donors. Total RNA was
      isolated and reverse-transcribed. Oxidative stress and DNA damage-signaling gene
      expression were analyzed using commercial PCR-based microarrays. Western blot
      analyses were conducted on selected proteins to verify the microarray results.
      Nuclear DNA damage foci were detected in the endothelium of ex vivo corneas by
      immunostaining for H2AX-Ser139. RESULTS: Four of 84 genes showed a statistically
      significant age-related difference in the expression of oxidative stress-related
      genes; however, Western blot analysis demonstrated an age-related increase in
      only 2 (cytoglobin and GPX-1) of 11 proteins tested. No age-related differences
      were detected in the expression of DNA damage-signaling genes. Western blot
      analysis of seven DNA damage-related proteins verified this finding. Intense
      nuclear staining of DNA damage foci was observed in nuclei within the central
      endothelium of older donors. Central endothelium from young donors consistently
      showed a low level of positive staining. CONCLUSIONS: HCECs respond to age
      related increases in oxidative nuclear DNA damage by forming DNA damage repair
      foci; however, they do not vigorously defend against or repair this damage by
      upregulating the expression of multiple oxidative stress or DNA damage-signaling
      genes.

PMID- 21087956
TI  - Figure ground discrimination in age-related macular degeneration.
AB  - PURPOSE: To investigate impairment in discriminating a figure from its background
      and to study its relation to visual acuity and lesion size in patients with
      neovascular age-related macular degeneration (AMD). METHODS: Seventeen patients
      with neovascular AMD and visual acuity <20/50 were included. Seventeen age
      matched healthy subjects participated as controls. Complete ophthalmologic
      examination was performed on all participants. The stimuli were photographs of
      scenes containing animals (targets) or other objects (distractors), displayed on
      a computer monitor screen. Performance was compared in four background
      conditions: the target in the natural scene; the target isolated on a white
      background; the target separated by a white space from a structured scene; the
      target separated by a white space from a nonstructured, shapeless background.
      Target discriminability (d') was recorded. RESULTS: Performance was lower for
      patients than for controls. For the patients, it was easier to detect the target
      when it was separated from its background (under isolated, structured, and
      nonstructured conditions) than it was when located in a scene. Performance was
      improved in patients with increasing exposure time but remained lower in
      controls. Correlations were found between visual acuity, lesion size, and
      sensitivity for patients. CONCLUSIONS: Figure/ground segregation is impaired in
      patients with AMD. A white space surrounding an object is sufficient to improve
      the object's detection and to facilitate figure/ground segregation. These results
      may have practical applications to the rehabilitation of the environment in
      patients with AMD.

PMID- 21087958
TI  - Predictors of short-term visual outcome after anti-VEGF therapy of macular edema
      due to central retinal vein occlusion.
AB  - PURPOSE: The purpose of this study was to analyze predictive factors for best
      corrected visual acuity (BCVA) after anti-VEGF treatment in patients with macular
      edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This
      prospective study enrolled treatment-naive patients with ME secondary to CRVO.
      BCVA, ophthalmoscopy, fundus photography, and spectral domain optical coherence
      tomography (SD-OCT) imaging were performed. SD-OCT was analyzed for integrity of
      the external limiting membrane (ELM), photoreceptor inner segments (IS), and
      outer segments (OS). Patients were treated with intravitreal bevacizumab (1.25
      mg) or ranibizumab (0.5 mg). BCVA outcome was analyzed 4 weeks after the first
      injection. RESULTS: Sixty-two eyes of 62 patients (39 men, 23 women; mean age: 67
      +/-16 years) were included. In 55%, the ELM was intact. These eyes also showed
      intact photoreceptor IS/OS in horizontal and vertical single scans. Disturbed ELM
      was seen in 45% and was accompanied by focal disintegration of IS/OS. Four weeks
      after injection, 58% showed clinically relevant increases of BCVA (>=5 letters).
      Mean BCVA ranged from 20 to 86 letters. The mean BCVA increase was 18 +/- 12
      letters in eyes with intact ELM compared with 4 +/- 10 letters with disturbed ELM
      (P < 0.001). CONCLUSIONS: Depending on the integrity of the outer retinal layers,
      the authors observed rapid and clinically relevant improvement in BCVA after the
      first anti-VEGF injection. In the development of an optimal treatment regime, the
      indication for treatment and re-treatment should be based on functional and
      morphologic findings, such as the deterioration of outer retinal layers. Intact
      ELM in SD-OCT imaging is associated with better visual outcomes after
      intravitreal anti-VEGF treatment in patients with ME secondary to CRVO.

PMID- 21087957
TI  - Polarized secretion of PEDF from human embryonic stem cell-derived RPE promotes
      retinal progenitor cell survival.
AB  - PURPOSE: Human embryonic stem cell-derived RPE (hES-RPE) transplantation is a
      promising therapy for atrophic age-related macular degeneration (AMD); however,
      future therapeutic approaches may consider co-transplantation of hES-RPE with
      retinal progenitor cells (RPCs) as a replacement source for lost photoreceptors.
      The purpose of this study was to determine the effect of polarization of hES-RPE
      monolayers on their ability to promote survival of RPCs. METHODS: The hES-3 cell
      line was used for derivation of RPE. Polarization of hES-RPE was achieved by
      prolonged growth on permeable inserts. RPCs were isolated from 16- to 18-week
      gestation human fetal eyes. ELISA was performed to measure pigment epithelium
      derived factor (PEDF) levels from conditioned media. RESULTS: Pigmented RPE-like
      cells appeared as early as 4 weeks in culture and were subcultured at 8 weeks.
      Differentiated hES-RPE had a normal chromosomal karyotype. Phenotypically
      polarized hES-RPE cells showed expression of RPE-specific genes. Polarized hES
      RPE showed prominent expression of PEDF in apical cytoplasm and a marked increase
      in secretion of PEDF into the medium compared with nonpolarized culture. RPCs
      grown in the presence of supernatants from polarized hES-RPE showed enhanced
      survival, which was ablated by the presence of anti-PEDF antibody. CONCLUSIONS:
      hES-3 cells can be differentiated into functionally polarized hES-RPE cells that
      exhibit characteristics similar to those of native RPE. On polarization, hES-RPE
      cells secrete high levels of PEDF that can support RPC survival. These
      experiments suggest that polarization of hES-RPE would be an important feature
      for promotion of RPC survival in future cell therapy for atrophic AMD.

PMID- 21087959
TI  - Three-dimensional imaging of macular inner structures in glaucoma by using
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To profile macular thickness changes in glaucoma by using three
      dimensional spectral-domain optical coherence tomography (3D-SD-OCT). METHODS:
      The study included 30 eyes with suspected glaucoma and preperimetric glaucoma
      (SGPPG) and 35 healthy eyes. The macular thickness, including those of the total
      retina, nerve fiber layer (NFL), and combined inner retinal layers (IRLs)
      NFL+ganglion cell layer (GCL)+inner plexiform layer (IPL)-was measured by 3D-SD
      OCT raster scans in a 6 mm(2) region. The average and sectoral thicknesses were
      calculated on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart and
      a ETDRS chart with a 45 degrees  rotation (glaucoma sector chart, GSC). RESULTS:
      The mean IRL thickness was significantly less in the SGPPG eyes than in the
      healthy eyes, but the mean total retinal and macular NFL thicknesses were not. In
      the SGPPG eyes, the IRLs were thinner in the outer macula than in the inner
      macula, in the inferior hemisphere than in the superior hemisphere, and in the
      temporal hemisphere than in the nasal hemisphere. The significantly thinned
      sectors were nearly identical on the GSC but only slightly overlapped on the
      ETDRS chart. The IRLs in the inferior temporal outer sector (GSC) had the
      greatest area under the receiver operating characteristic curve, which was
      significantly greater than those for the IRLs over the entire macula, inferior
      hemiretinal region, and inferior outer hemicircular region (macular subfields),
      and that for the circumpapillary NFL in the inferior sectors (P = 0.001-0.036).
      CONCLUSIONS: Macular IRL thickness measured by using 3D-SD-OCT is useful for
      profiling macular atrophy in SGPPG.

PMID- 21087960
TI  - Tear film, contact lens, and patient factors associated with corneal staining.
AB  - PURPOSE: The purpose of this study was to examine ocular surface and tear film,
      contact lens, care solution, medical, and patient-related factors that are
      associated with corneal staining in contact lens wearers. METHODS: In this cross
      sectional/nested case-control study, in addition to the assessment of corneal
      staining with fluorescein, a variety of tear film and ocular surface, contact
      lens, and patient-related factors were examined. Poisson regression models were
      used to examine the relation between corneal staining and these factors. RESULTS:
      Data from 413 patients were eligible for the analyses described. The average age
      was 30.6 +/- 11.1 years, and 277 (67.1%) of the patients were women. Several
      factors were shown to be related to increased corneal staining in multivariate
      modeling, including increased daily wearing times (P = 0.0006), lower income (P =
      0.0008), lissamine green conjunctival staining (P = 0.002), contact lens
      deposition (P = 0.007), increased tear meniscus height (P = 0.007), and decreased
      hydrogel nominal water content (P = 0.02). The wearing of silicone hydrogels (as
      opposed to hydrogels) was protective against corneal staining (P = 0.0004).
      Notably, neither contact lens care solutions nor disinfectants were associated
      with corneal staining. CONCLUSIONS: Corneal staining in contact lens wearers
      continues to be a frequent, but not well understood, outcome. These data suggest
      that contact lens factors (water content, material, wearing time, and deposition)
      are more generally associated with corneal staining than are contact lens care
      solutions or other ocular surface and tear film, demographic, or medical factors.

PMID- 21087961
TI  - Low levels of hydrogen peroxide stimulate corneal epithelial cell adhesion,
      migration, and wound healing.
AB  - PURPOSE: Intracellular reactive oxygen species have been reported to associate
      with growth factor and integrin signalings in promoting cell adhesion in many
      cell types. This study is to explore if exogenous H(2)O(2) at low levels can be
      beneficial to cell adhesion, migration, and wound healing. METHODS: Primary
      rabbit corneal epithelial cells treated with 0-70 MUM H(2)O(2) were tested for
      viability by MTT assay, adhesion by centrifugation assay, focal contacts of
      vinculin and F-actin by immunofluorescence, activated Src(pY416), EGF receptor
      (pY845), vinculin(pY1065), FAK(pY397), and FAK(pY576) by immunoblotting. Cell
      migration was examined with 0-50 MUM H(2)O(2) using the scratch wound technique.
      Corneal wound healing of ex vivo pig model and in vivo mouse model was examined
      using H(2)O(2) with and without antioxidant N-acetylcysteine (NAC). RESULTS:
      Compared with the untreated control, H(2)O(2) at 10-50 MUM stimulated cell
      viability and facilitated adhesion and migration with clear induction of vinculin
      rich focal adhesions and F-actin-containing stress fibers by increasing activated
      Src, FAK(pY576), and vinculin(pY1065). H(2)O(2) also increased phosphorylation of
      EGFR(Y845) parallel to that of activated Src, but both were eliminated by NAC and
      PP1 (Src inhibitor). Finally, H(2)O(2) induced faster wound healing in cornea
      both in vitro and in vivo, but the healing was diminished by NAC. CONCLUSIONS:
      These findings suggest that H(2)O(2) at low levels promotes cell adhesion,
      migration, and wound healing in cornea cells or tissue, and the interaction of
      H(2)O(2) with Src plays a major role.

PMID- 21087962
TI  - Transcriptional regulation of activating transcription factor 4 under oxidative
      stress in retinal pigment epithelial ARPE-19/HPV-16 cells.
AB  - PURPOSE: Oxidative stress plays an important role in the pathogenesis of various
      ocular diseases such as retinopathy, glaucoma, and age-related macular
      degeneration. Activating transcription factor 4 (ATF4) is induced by various
      stressors, including endoplasmic reticulum (ER) and oxidative stress, and ATF4
      expression is regulated translationally through the PERK pathway of eIF2alpha
      phosphorylation. Transcriptional regulation of the ATF4 gene under oxidative
      stress was investigated in human papillomavirus 16 (HPV-16)-transformed retinal
      pigment epithelial ARPE-19/HPV-16 cells. METHODS: Retinal pigment epithelial
      cells, trabecular meshwork cells, and corneal endothelial cells were treated with
      anoxia and thapsigargin (TG). Gene expression of ATF4 and nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2) and transcription factors was investigated by
      Western blot analysis, reporter assays, chromatin immunoprecipitation (ChIP)
      assays, and small interfering (si)RNA strategies. Cellular sensitivity to
      oxidative stress was determined. RESULTS: The expression of two transcriptional
      factors, ATF4 and Nrf2, was significantly induced by anoxia and TG. The Nrf2
      regulator Keap1 was downregulated by anoxia. Downregulation of Nrf2 abolished
      ATF4 expression. On the other hand, downregulation of Keap1 enhanced the
      expression of both Nrf2 and ATF4. The promoter activity of ATF4 was
      transactivated by the co-transfection of Nrf2 expression plasmids and reduced by
      the transfection of Nrf2-specific siRNA. The ChIP assays demonstrated that Nrf2
      bound to the promoter of the ATF4 gene. Nrf2 downregulation nearly abolished the
      ATF4 induction by anoxia and TG. Consistent with these findings, the promoter
      activity of ATF4 was augmented by treatment with TG, HCA, H(2)O(2), and anoxia.
      However, stress induction of ATF4 promoter activity was observed, even when a
      mutation was introduced into the antioxidant-responsive elements site.
      Furthermore, stress induction of the ATF4 promoter was completely abolished when
      the 5' untranslated region of the ATF4 gene was deleted. Downregulation of ATF4
      rendered ARPE-19/HPV-16 cells sensitive to oxidative stress. CONCLUSIONS: These
      results suggest that the stress induction of ATF4 is significantly regulated
      transcriptionally through a Nrf2-dependent mechanism and may be a double-edged
      sword in the pathogenesis of various retinopathies.

PMID- 21087964
TI  - The use of mucoadhesive polymers to enhance the hypotensive effect of a melatonin
      analogue, 5-MCA-NAT, in rabbit eyes.
AB  - PURPOSE: 5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin
      receptor agonist) produces a clear intraocular pressure (IOP) reduction in New
      Zealand White rabbits and glaucomatous monkeys. The goal of this study was to
      evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence
      of cellulose derivatives, some of them with bioadhesive properties, as well as to
      determine whether these formulations were well tolerated by the ocular surface.
      METHODS: Formulations were prepared with propylene glycol (0.275%), carboxymethyl
      cellulose (CMC, 0.5% and 1.0%) of low and medium viscosity and
      hydroxypropylmethyl cellulose (0.3%). Quantification of 5-MCA-NAT (100 MUM) was
      assessed by HPLC. In vitro tolerance was evaluated by the MTT method in human
      corneal-limbal epithelial cells and normal human conjunctival cells. In vivo
      tolerance was analyzed by biomicroscopy and specular microscopy in rabbit eyes.
      The ocular hypotensive effect was evaluated measuring IOP for 8 hours in rabbit
      eyes. RESULTS: All the formulations demonstrated good in vitro and in vivo
      tolerance. 5-MCA-NAT in CMC medium viscosity 0.5% was the most effective at
      reducing IOP (maximum IOP reduction, 30.27%), and its effect lasted approximately
      7 hours. CONCLUSIONS: The hypotensive effect of 5-MCA-NAT was increased by using
      bioadhesive polymers in formulations that are suitable for the ocular surface and
      also protective of the eye in long-term therapies. The use of 5-MCA-NAT combined
      with bioadhesive polymers is a good strategy in the treatment of ocular
      hypertension and glaucoma.

PMID- 21087963
TI  - Lacritin, a novel human tear glycoprotein, promotes sustained basal tearing and
      is well tolerated.
AB  - PURPOSE: Lacritin is a novel human tear glycoprotein that promotes basal tear
      peroxidase secretion by rat lacrimal acinar cells in vitro. This study
      investigates whether lacritin is prosecretory when added topically to the ocular
      surface of normal living rabbits, and if so, what is its efficacy and
      tolerability versus cyclosporine and artificial tears. METHODS: Purified
      recombinant human lacritin (1, 10, 50, or 100 MUg/mL), inactive lacritin
      truncation mutant C-25 (10 MUg/mL), cyclosporine (0.05%), or artificial tears
      were topically administered to eyes of normal New Zealand White rabbits either as
      a single dose or three times daily for 14 days with monitoring of basal tear
      production. Basal tearing under proparacaine anesthesia was repeatedly assessed
      throughout and 1 week after chronic treatment ceased. Eyes were examined weekly
      by slit-lamp biomicroscopy. RESULTS: Lacritin acutely increased basal tearing to
      30% over vehicle at 240 minutes. Three times daily treatment with 10-100 MUg/mL
      lacritin was well tolerated. Basal tearing became progressively elevated 4, 7,
      and 14 days later and was 50% over baseline (50 MUg/mL lacritin) 1 week after
      treatment had ceased. Cyclosporine elevated tearing to a similar level on days 4
      and 7 but had little or no effect on day 14 and had returned to baseline 1 week
      after ending treatment. C-25 and artificial tears had no effect. CONCLUSIONS:
      Lacritin acutely stimulates basal tear flow that is sustained for at least 240
      minutes. Two weeks of lacritin treatment three times daily was well tolerated and
      progressively elevated the basal tear flow. One week after treatment ended, basal
      tearing was still 50% over baseline. In contrast, cyclosporine triggered mild to
      moderate corneal irritation and a temporary elevation in tearing.

PMID- 21087965
TI  - Impaired angiogenic response in the cornea of mice lacking tenascin C.
AB  - PURPOSE: This study investigated the effects of loss of tenascin C (TNC) in the
      development of neovascularization in a corneal stroma in mice. Cell culture study
      was also conducted to clarify the roles of TNC in the expression of vascular
      endothelial growth factor (VEGF) and transforming growth factor (TGF)beta1 in
      fibroblasts and macrophages. METHODS: Ocular fibroblasts and macrophages from
      wild-type (WT) and TNC-null (KO) mice were used to study the role of TNC in the
      expression of VEGF and TGFbeta1. The effects of the absence of TNC on angiogenic
      gene expression, inflammatory cell invasion, and cornea neovascularization in the
      corneal stroma were then evaluated after cauterization of the center of the
      cornea in mice. Histologic, immunohistochemical, and mRNA expression analyses
      were performed. RESULTS: Absence of TNC suppressed expression of VEGF and
      counteracted upregulation of TGFbeta1 by exogenous TGFbeta1 in ocular fibroblast
      culture. Such effects of the absence of TNC were not observed in cultured
      macrophages. Absence of TNC attenuated expression of both VEGF and TGFbeta1 mRNA
      as well as neovascularization into the stroma after cauterization at the center
      of the cornea in mice. Absence of TNC suppressed macrophages, but not
      neutrophils, invading the cauterized cornea. CONCLUSIONS: TNC is involved in
      angiogenic gene expression in ocular fibroblasts in vitro and in vivo and is
      required for macrophage invasion and neovascularization of injured corneal
      stroma.

PMID- 21087966
TI  - Predictors of normal optic nerve head, retinal nerve fiber layer, and macular
      parameters measured by spectral domain optical coherence tomography.
AB  - PURPOSE: To evaluate the effects of signal strength, age, sex, optic disc size,
      and axial length on the normal optic nerve head (ONH), retinal nerve fiber layer
      (RNFL), and macular measurements with spectral domain optical coherence
      tomography (SD-OCT). METHODS: In an observational, cross-sectional study, 119
      eyes of 60 normal subjects of Indian origin underwent ONH, RNFL, and macular
      imaging with SD-OCT during the same visit. Linear mixed-modeling methods were
      used to evaluate the effects of signal strength, age, sex, optic disc area, and
      axial length on ONH, RNFL, and macular measurements. RESULTS: ONH rim
      measurements increased and cup measurements decreased with increasing signal
      strengths. For a 10-unit increase in signal strength, total rim area increased by
      a mean of 0.1 mm(2). ONH measurements also increased with increasing optic disc
      size. Rim measurements decreased and cup measurements increased with increasing
      axial length. None of the predictors influenced RNFL measurements. Macular inner
      retinal thickness decreased by a mean of 1.7 MUm and macular full retinal
      thickness decreased by an average of 3.4 MUm for every decade's increase in age.
      Sex did not influence any of the measurements. CONCLUSIONS: Signal strength,
      optic disc size, and axial length had a significant effect on ONH measurements,
      whereas age had a significant effect on macular measurements. None of the
      predictors evaluated influenced the RNFL measurements. These predictors should be
      considered when evaluating change in the structural measurements in glaucoma over
      time.

PMID- 21087967
TI  - Modulating neuromuscular junction density changes in botulinum toxin-treated
      orbicularis oculi muscle.
AB  - PURPOSE: Botulinum toxin A is the most commonly used treatment for blepharospasm,
      hemifacial spasm, and other focal dystonias. Its main drawback is its relatively
      short duration of effect. The goal of this study was to examine the ability of
      corticotropin releasing factor (CRF) or antibody to insulin growth factor I
      receptor (anti-IGFIR) to reduce the up-regulation of neuromuscular junctions that
      are associated with return of muscle function after botulinum toxin treatment.
      METHODS: Eyelids of adult rabbits were locally injected with either botulinum
      toxin alone or botulinum toxin treatment followed by injection of either CRF or
      anti-IGFIR. After one, two, or four weeks, the orbicularis oculi muscles within
      the treated eyelids were examined for density of neuromuscular junctions
      histologically. RESULTS: Injection of botulinum toxin into rabbit eyelids
      resulted in a significant increase in the density of neuromuscular junctions at
      one and two weeks, and an even greater increase in neuromuscular junction density
      by four weeks after treatment. Treatment with either CRF or anti-IGFIR completely
      prevented this increase in neuromuscular junction density. CONCLUSIONS: The
      return of function after botulinum toxin-induced muscle paralysis is due to
      terminal sprouting and formation of new neuromuscular junctions within the
      paralyzed muscles. Injection with CRF or anti-IGFIR after botulinum toxin
      treatment prevents this sprouting, which in turn should increase the duration of
      effectiveness of single botulinum toxin treatments. Future physiology studies
      will address this. Prolonging botulinum toxin's clinical efficacy should decrease
      the number of injections needed for patient muscle spasm relief, decreasing the
      risk of negative side effects and changes in drug effectiveness that often occurs
      over a lifetime of botulinum toxin exposure.

PMID- 21087968
TI  - In vivo efficacy of bone marrow stromal cells coated with beta-tricalcium
      phosphate for the reconstruction of orbital defects in canines.
AB  - PURPOSE: To repair the segmental orbital rim defects of dogs with three
      dimensional (3D) tissue-engineered constructs derived from culturing autogenous
      bone marrow stromal cells (BMSCs) on beta-tricalcium phosphate (beta-TCP)
      scaffolds. METHODS: A 25-mm segmental defect on the canine inferior orbital rim
      was created. BMSCs were isolated and osteogenically induced in vitro, then were
      seeded onto 3D beta-TCP scaffolds and implanted to repair the orbital defects
      after 5 days of cultivation. The group of noninduced BMSC/beta-TCP, beta-TCP
      alone, and the normal inferior orbital rim were set as controls. The orbits of
      all groups had spiral computed tomography (CT) scans 1, 4, 8, and 12 weeks after
      surgery. Gross examination, bone density, microCT, and histologic measurements
      were performed 12 weeks after surgery. The results were analyzed to evaluate the
      extent of bone repair. RESULTS: Twelve weeks after surgery, CT examination
      revealed good inferior orbital rim recovery in the induced BMSC/beta-TCP group,
      and the bone density was 0.30 +/- 0.03 g/cm(2) with no dominant variance,
      compared with the normal control (P > 0.05). MicroCT and histologic examination
      confirmed that the implantations led to good repair of the defects. Pore-like
      spongy bone surrounded the implants through the section plane, with some residue
      remaining in the center. In contrast, the noninduced BMSC/beta-TCP implants were
      not fully repaired, and nonunion was evident. The bony density for this group was
      0.23 +/- 0.07 g/cm(2), which was significantly lower than that of the control
      group (P < 0.05). The beta-TCP group was largely held by fibrous tissues.
      CONCLUSIONS: Engineered bone from induced BMSCs and 3D biodegradable beta-TCP can
      efficiently repair critical-sized segmental orbital defects in dogs.

PMID- 21087969
TI  - Non-damaging retinal phototherapy: dynamic range of heat shock protein
      expression.
AB  - PURPOSE: Subthreshold retinal phototherapy demonstrated clinical efficacy for the
      treatment of diabetic macular edema without visible signs of retinal damage. To
      assess the range of cellular responses to sublethal hyperthermia, expression of
      the gene encoding a 70 kDa heat shock protein (HSP70) was evaluated after laser
      irradiation using a transgenic reporter mouse. METHODS: One hundred millisecond,
      532 nm laser exposures with 400 MUm beam diameter were applied to the retina
      surrounding the optic nerve in 32 mice. Transcription from the HSP70 promoter was
      assessed relative to the control eye using a bioluminescence assay at 7 hours
      after laser application. The retinal pigmented epithelium (RPE) viability
      threshold was determined with a fluorescence assay. A computational model was
      developed to estimate temperature and the extent of cell damage. RESULTS: A
      significant increase in HSP70 transcription was found at exposures over 20 mW,
      half the threshold power for RPE cell death. Computational modeling estimated
      peak temperature T = 49 degrees C at HSP70 expression threshold. At RPE viability
      threshold, T = 57 degrees C. Similar temperatures and damage indices were
      calculated for clinical subvisible retinal treatment parameters. CONCLUSIONS:
      Beneficial effects of laser therapy have been previously shown to extend beyond
      those resulting from destruction of tissue. One hundred millisecond laser
      exposures at approximately half the threshold power of RPE damage induced
      transcription of HSP70, an indication of cellular response to sublethal thermal
      stress. A computational model of retinal hyperthermia can guide further
      optimization of laser parameters for nondamaging phototherapy.

PMID- 21087970
TI  - Repeatability of manual subfoveal choroidal thickness measurements in healthy
      subjects using the technique of enhanced depth imaging optical coherence
      tomography.
AB  - PURPOSE: The aim of this study was to investigate the repeatability of manual
      measurements of choroidal thickness in healthy subjects imaged on spectral domain
      optical coherence tomography (OCT) using the enhanced depth imaging (EDI)
      technique. METHODS: Fifty consecutive, healthy, young, adult volunteers with no
      known eye disease were enrolled prospectively. Two good-quality horizontal and
      vertical line scans through the fovea were obtained for each eye. Using the
      manual calipers provided by the software of the proprietary device, two
      experienced OCT readers measured the subfoveal choroidal thickness (SFCT) of the
      horizontal and vertical line scans for all eyes. The readers were masked to each
      other's readings. Intraobserver, interobserver, and intrasession coefficients of
      repeatability (CRs) were calculated. RESULTS: Mean (standard deviation [SD]) age
      of the study subjects was 38 (5) years (range, 30-49 years). Mean (SD) subfoveal
      choroidal thickness was 332 (90) MUm (right eyes) and 332 (91) MUm (left eyes).
      Intraobserver CR was approximately 23 (95% confidence interval [CI], 19-26) MUm,
      whereas interobserver and intrasession CRs were greater at 32 (95% CI, 30-34) and
      34 (95% CI, 32-36) MUm, respectively. There was no significant difference in SFCT
      between all pairs of SFCT measurements except for the two intrasession vertical
      line scans. CONCLUSION: A change of >32 MUm was likely to exceed interobserver
      variability in SFCT. Future studies are required to estimate the repeatability of
      SFCT measurements in patients with chorioretinal pathology.

PMID- 21087971
TI  - Agonists at the serotonin receptor (5-HT(1A)) protect the retina from severe
      photo-oxidative stress.
AB  - PURPOSE: 5-HT(1A) agonists are neuroprotective in CNS injury models. The authors
      evaluated the efficacy of 5-HT(1A) agonists to protect the retina from severe
      blue light-induced photo-oxidative damage. METHODS: Albino rats were dosed
      (subcutaneously) with AL-8309A, 8-OH DPAT, or buspirone once or three times
      before 6-hour exposure to blue light. Electroretinograms (ERGs) were measured to
      assess retinal function, and retinal damage was evaluated by light microscopy.
      Topical ocular dosing with 1.75% AL-8309B was also evaluated. Rats were dosed
      with WAY-100635, a 5-HT(1A) antagonist, to determine whether protection required
      activation of the 5-HT(1A) receptor. RESULTS: ERG response amplitudes were
      significantly (P < 0.05) depressed more than 66% in vehicle-dosed rats after
      light exposure. ERGs were significantly higher in rats treated with AL-8309A (0.1
      30 mg/kg), 8-OH DPAT (0.1-1 mg/kg), buspirone (5-20 mg/kg) or topical ocular with
      1.75% AL-8309B. Retinas from AL-8309A and 8-OH DPAT-treated rats were devoid of
      histologic lesions. Significant protection was measured in rats dosed once 0, 24,
      or 48 hours before light exposure. Protection provided by dosing with AL-8309B or
      8-OH DPAT was inhibited in rats predosed with WAY-100635. CONCLUSIONS: 5-HT(1A)
      agonists provided potent and complete functional and structural protection.
      Protection was inhibited by treatment with WAY-100635, confirming the requirement
      for activating the 5-HT(1A) receptor in initiating this survival pathway. Single
      dose experiments with AL-8309A suggest that the mechanism of protection is
      rapidly activated and protection persists for 48 hours. AL-8309B (1.75%) was
      effective after topical ocular dosing. AL-8309B is under evaluation in the clinic
      and may be useful in treating age-related macular degeneration.

PMID- 21087972
TI  - Improving reading speed for people with central vision loss through perceptual
      learning.
AB  - PURPOSE: Perceptual learning has been shown to be effective in improving visual
      functions in the normal adult visual system, as well as in adults with amblyopia.
      In this study, the feasibility of applying perceptual learning to enhance reading
      speed in people with long-standing central vision loss was evaluated. METHODS:
      Six observers (mean age, 73.8) with long-standing central vision loss practiced
      an oral sentence-reading task, with words presented sequentially using rapid
      serial visual presentation (RSVP). A pre-test consisted of measurements of visual
      acuities, RSVP reading speeds for six print sizes, the location of the preferred
      retinal locus for fixation (fPRL), and fixation stability. Training consisted of
      six weekly sessions of RSVP reading, with 300 sentences presented per session. A
      post-test, identical with the pre-test, followed the training. RESULTS: All
      observers showed improved RSVP reading speed after training. The improvement
      averaged 53% (range, 34-70%). Comparisons of pre- and post-test measurements
      revealed little changes in visual acuity, critical print size, location of the
      fPRL, and fixation stability. CONCLUSIONS: The specificity of the learning
      effect, and the lack of changes to the fPRL location and fixation stability
      suggest that the improvements are not due to observers adopting a retinal
      location with better visual capability, or an improvement in fixation. Rather,
      the improvements are likely to represent genuine plasticity of the visual system
      despite the older ages of the observers, coupled with long-standing sensory
      deficits. Perceptual learning might be an effective way of enhancing visual
      performance for people with central vision loss.

PMID- 21087973
TI  - Relationship of central corneal thickness with optic disc parameters: the
      Singapore Malay Eye Study.
AB  - PURPOSE: To examine the relationship of central corneal thickness (CCT) with
      optic disc parameters measured by confocal scanning laser ophthalmoloscopy in a
      Malay population. METHODS: This was a population-based cross-sectional study of
      Asian Malay adults aged 40-80 years living in Singapore. Participants had a
      standardized interview, examination, and imaging at a study clinic. CCT was
      measured with an ultrasound pachymeter. Confocal scanning laser imaging was
      performed on all participants to obtain optic disc parameters. Multivariate
      regression analyses controlling for age, sex, intraocular pressure, and other
      potentially confounding factors were conducted separately for disc area, rim
      area, cup-to-disc ratio, and mean cup depth. RESULTS: Of the 3280 participants in
      the study, 2525 (77.0%) right eyes with reliable confocal scanning laser
      tomography images were included in this analysis, with 48 eyes defined to have
      primary open-angle glaucoma (POAG). In POAG subjects, CCT was positively
      correlated with rim area (regression coefficient of 0.372 mm(2) per 100 MUm CCT
      increase; P = 0.035) and negatively correlated with cup-to-disc area ratio (
      0.160 per 100 MUm CCT increase; P = 0.024). There was no relationship between CCT
      and disc size (P = 0.088). In the 2468 subjects without glaucoma, there were no
      associations between CCT and confocal scanning laser tomography parameters.
      CONCLUSIONS: In this population-based study, decreased CCT was associated with
      lower rim area and greater cup-to-disc area in subjects with POAG, but not in
      subjects without glaucoma.

PMID- 21087977
TI  - Clinical implication of the antidiuretic hormone (ADH) receptor antagonist
      mozavaptan hydrochloride in patients with ectopic ADH syndrome.
AB  - Ectopic antidiuretic hormone syndrome is a medical emergency characterized by
      dilutional hyponatremia. Clinical effectiveness of the vasopressin V2 receptor
      antagonist mozavaptan was evaluated in 16 patients. In short-term (7-day)
      treatment with the drug, serum sodium concentration (mean +/- standard deviation)
      significantly (P = 0.002) increased from 122.8 +/- 6.7 to 133.3 +/- 8.3 mEq/l,
      and symptoms due to hyponatremia were improved. On the basis of these results,
      mozavaptan (Physuline((r))) was approved as an orphan drug for the treatment of
      the syndrome in 2006 in Japan. During the 43 months following its launch, 100
      patients have been treated with the drug; overall clinical effects of the drug
      were found similar to those of this clinical trial. Clinically, mozavaptan may
      allow hyponatremic patients to be treated by aggressive cancer chemotherapy with
      platinum-containing drugs. Moreover, the drug may free patients from strict fluid
      intake restrictions and thereby improve their quality of life.

PMID- 21087978
TI  - Spermatocytic seminoma: review of the literature and description of a new case of
      the anaplastic variant.
AB  - The aims of this paper were to review the literature of Spermatocytic Seminoma
      (SS) updating its clinico-pathological features and to present a new case of the
      exceptionally rare variant of this tumor known as anaplastic which only five
      cases have been reported. Many studies have confirmed that SS is a distinct
      neoplasm both clinically and pathologically from classical Seminoma and it
      differs from the latter especially in regard to behavior, characterized by an
      almost complete inability to metastasize with only very few convincing examples
      described with metastatic behavior. There is general agreement that orchidectomy
      is sufficient therapy for SS and that surveillance following surgery is the
      preferred management option. Surprisingly, the presence of an anaplastic
      component does not seem to impact on this excellent prognosis. Very different is
      the case of sarcomatous transformation, for which further therapy after
      orchiectomy is advisable.

PMID- 21087979
TI  - Colonization of intestinal endometriosis by benign colonic mucosa: a pattern
      potentially misdiagnosed as invasive mucinous carcinoma.
AB  - Endometriosis is well known for creating diagnostic pitfalls for pathologists. It
      may produce masses mimicking neoplasms or cause diagnostic quandaries,
      particularly when the patient age, location, and/or epithelial appearance are
      atypical. This study reports a patient with endometriosis causing rectal bleeding
      and involving the cecum. It produced a mass clinically considered appendiceal.
      The endometriosis was focally lined by intestinal epithelium including Paneth
      cells. In the deep endometriotic glands embedded within intestinal wall, direct
      fusion of the intestinal and the endometrial epithelium-the benign intestinal
      epithelium apparently colonizing the endometriotic foci-was found. The mass
      effect, plus deep-seated intestinal epithelium, closely mimicked invasive well
      differentiated mucinous carcinoma. This is yet another peculiar presentation of
      endometriosis with potential for misinterpretation as a more serious condition,
      specifically well-differentiated mucinous carcinoma of the cecum or appendix.

PMID- 21087980
TI  - Unusual presentation of benign cystic brenner tumor with exuberant psammomatous
      calcifications.
AB  - Transitional cell tumors of the ovary comprise about 1% to 2% of all ovarian
      neoplasms. Most of these tumors are benign Brenner tumors and account for about
      5% of benign surface epithelial-stromal tumors. Spicules of calcifications are
      found in the stroma of about 50% of benign Brenner tumors. Although diagnostic
      challenges might occur more frequently with either of the borderline or malignant
      Brenner tumors, this problem is not that common when diagnosing a benign Brenner
      tumor. This study reports a case of benign Brenner tumor with exuberant
      dystrophic calcifications that obscured most of the epithelium and posed a
      diagnostic challenge in differentiating it from the more common malignant
      counterparts such as serous carcinoma and specifically psammocarcinoma.

PMID- 21087981
TI  - Assessment of immunohistochemistry for p16INK4 and high-risk HPV DNA by in situ
      hybridization in esophageal squamous cell carcinoma.
AB  - The role of high-risk human papillomavirus (HPV) in the pathogenesis of
      esophageal squamous cell carcinoma (ESCC) remains unclear. p16(INK4) is used as a
      surrogate marker to detect HPV-related tumors but has had discrepant results in
      ESCC. In this study, 32 cases of ESCC were examined to determine the relationship
      between p16(INK4) expression and high-risk HPV. All the tumors were stained by
      immunohistochemistry for p16(INK4). Tumors having p16(INK4) nuclear and/or
      nuclear and cytoplasmic expression were considered positive. Tumors positive for
      p16(INK4) expression were tested for high-risk HPV by in situ hybridization
      (ISH). In all, 20 cases of ESCC (63%) showed only cytoplasmic staining for
      p16(INK4), and 11 cases (34%) showed both cytoplasmic and nuclear staining for
      p16(INK4); 4 cases (13%) showed no staining for p16(INK4). None of the p16(INK4) 
      positive cases were positive for high-risk HPV by ISH. These results indicate
      that p16(INK4) expression in ESCC does not correlate with the presence of high
      risk HPV DNA by ISH. High-risk HPV does not seem to play a major role in the
      carcinogenesis of ESCC in low-risk areas.

PMID- 21087982
TI  - Morphological parameters associated with perineural invasion (PNI) in carcinoma
      of the cervix uteri.
AB  - The study determines morphological features that are associated with perineural
      invasion (PNI) in patients with cervical carcinoma (CX). Histological slides from
      194 patients from surgically treated squamous cell carcinoma were re-examined for
      PNI and correlated to morphological factors of tumor growth. Material from 68
      patients (35.1%) represented PNI. PNI was significantly correlated with advanced
      tumor stage (P < .001). Patients with deep cervical stromal invasion (>66%)
      showed more PNI than those with more superficial invasion (41% vs 16.9%; P =
      .001). Tumors with spray-like PI showed significantly more PNI (48.4%) when
      compared with finger-like PI (26.7%) and those with pushing borders (18.8%; P =
      .007). Strong peritumoral desmoplastic stromal reaction and absence of
      peritumoral inflammation were associated with a higher frequency of PNI (P <
      .001). PNI is associated with advanced tumor stage, deep cervical stromal
      invasion (>66%), high grade of tumor cell dissociation (ie, spray-like pattern of
      invasion), strong peritumoral desmoplastic stromal reaction, and reduced
      peritumoral inflammation.

PMID- 21087983
TI  - CD34, CD117, and Ki-67 expression in phyllodes tumor of the breast: an
      immunohistochemical study of 33 cases.
AB  - Phyllodes tumors (PTs) of the breast are biphasic lesions, comprising an
      epithelial component set within a neoplastic spindle-celled stroma. These tumors
      have been classified as benign, borderline, and malignant based on a combination
      of histological criteria, including stromal cellularity, nuclear pleomorphism,
      mitotic rate, stromal overgrowth, and margin appearance. The aim of this study
      was to evaluate the expression of CD34, CD117 (c-kit), and Ki-67 in PT of the
      breast and attempt to correlate the staining pattern with tumor grade by
      morphology. Immunohistochemical expression of CD117, CD34, and Ki-67 was studied
      on formalin-fixed, paraffin-embedded archival tissue material from 33 cases of
      PT. Histologically, there were 21 benign, 6 borderline, and 6 malignant (high
      grade) tumors. All 6 histologically malignant PTs were positive for CD117 (100%),
      but only 1 marked with CD34 (16.7%). Borderline PTs frequently coexpressed CD34
      and CD117 (66.7%). The benign PTs, on the other hand, most commonly (52.4%)
      showed a CD34(+)/CD117(-) immunoprofile with 33.3% cases coexpressing the
      markers: that is, CD34(+)/CD117(+). Although most benign PTs (80.6%) showed a Ki
      67 of <2%, a few cases showed slightly higher proliferation indices. This study
      indicates that CD34 and CD117 are differentially expressed in benign and
      malignant PTs. These markers, therefore, in combination, may be used as an
      adjunct to morphology in the subclassification of PTs.

PMID- 21087984
TI  - Benign salivary gland tissue inclusion in a pulmonary hilar lymph node from a
      patient with invasive well-differentiated adenocarcinoma of the lung: a potential
      misinterpretation for the staging of carcinoma.
AB  - Benign epithelial and nonepithelial inclusions have been found in lymph nodes in
      multiple body sites. These inclusions have been seen in cervical, axillary,
      mediastinal, abdominal, and pelvic lymph nodes. They appear as benign epithelial,
      parathyroid, decidual, mesothelial, angiolipomatous, nevus cells, or Tamm
      Horsfall protein. Although heterotopic salivary gland tissue is not infrequent in
      paraparotid lymph nodes, it has only been described in lymph nodes of the
      pulmonary hilum once. A 68-year-old woman with gastric lymphoma now in remission
      presented for routine follow-up and was found to have a lung mass. After a fine
      needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph node
      dissection were performed. Histological sections of lung demonstrated a well
      differentiated adenocarcinoma and one lymph node, which displayed a subcapsular
      nest of well-formed salivary glands occupying approximately one third of the
      nodal tissue. The inclusion was composed of acinar cells of both serous and
      mucinous types, but ductal type of cells were not seen. Identification of
      heterotopic tissue in lymph nodes is of great importance for patient management.
      Misdiagnosing benign glandular inclusions for metastasis could potentially lead
      to incorrect tumor staging. Benign salivary gland tissue inclusions should be
      considered in the differential diagnosis when evaluating for metastatic
      adenocarcinoma. The salivary gland inclusion in pulmonary hilar lymph node may be
      histogenetically related to the minor salivary glands, which are located within
      the bronchial submucosa.

PMID- 21087985
TI  - Chondroid tenosynovial giant cell tumor: a clinicopathological and
      immunohistochemical analysis of 5 new cases.
AB  - Tenosynovial giant cell tumor (TGCT) arises from the synovium of joints or tendon
      sheaths. Chondroid metaplasia in TGCT is rare with only 4 well-documented cases
      reported in the literature. The authors describe the morphological features and
      immunophenotype of 5 new cases of chondroid TGCT emphasizing a broader range of
      matrix patterns in these tumors and an expanded immunophenotype, specifically,
      staining for clusterin and podoplanin which have recently been found to be
      expressed in conventional TGCTs. Chondroid metaplasia was extensive in 3 cases.
      Matrix patterns included chondromyxoid, chondro-osseous, hyaline-like, and lace
      like calcification similar to that seen in chondroblastoma. The authors conclude
      that chondroid TGCT is a rare, distinct synovial tumor with a predilection for
      the temporomandibular joint that has a similar immunophenotype as conventional
      TGCT. Chondroid metaplasia may be extensive and have a variety of matrix
      patterns. Chondroid TGCT needs to be distinguished from other chondroid lesions,
      including chondroblastoma and chondrosarcoma.

PMID- 21087986
TI  - Diffuse large B-cell lymphoma involving the central nervous system.
AB  - Lymphomas involving the central nervous system are recognized increasingly in
      immunocompetent as well as immunosuppressed individuals, and the majority of the
      cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to
      compare the immunophenotype, clinicopathological features, and association with
      Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3
      different clinical situations: primary, in immunocompetent patients; "primary,"
      in immunosuppressed patients; and in patients with secondary involvement by
      systemic lymphoma. The authors reviewed the clinicopathological features,
      morphology, immunophenotype (according to germinal-center B-cell-like and
      nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL
      of the CNS, including 25 primary cases, 5 associated with immunosuppression, and
      6 cases with secondary involvement. Survival was evaluated in 15 cases of primary
      CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of
      lymphomas were EBV-positive; both occurred in immunosuppressed patients.
      Separation into germinal-center and non-germinal center subtypes by an
      immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83%
      of the cases associated with immunosuppression were of non-germinal-center
      subtype, respectively. Patients with non-germinal-center immunophenotype showed
      significantly worse survival than those with CNS lymphomas of the germinal-center
      subtype.

PMID- 21087987
TI  - Angiolipoma of the female breast: clinicomorphological correlation of 52 cases.
AB  - The authors analyzed 52 cases of female breast angiolipoma (AL). Age distribution
      was 25 to 80 years of age (56.81 +/- 12.78). Most cases showed vascularity below
      50%, and 14 cases had vascularity >50%. Cellular and low-vascularity ALs had
      different clinical and radiological presentations. The mean size was 7.00 +/-
      3.62 mm for cellular ALs and 19.61 +/- 7.58 mm for low-vascularity ALs. In any
      paucicellular area, the authors could identify a cluster of at least 3
      interconnected vessels. The endothelium was mostly flat with uniform,
      hyperchromatic nuclei, and mitoses and nucleoli were absent. Fibrin thrombi in
      proliferating capillaries were noted in 96% of cases. Low-vascularity AL can be
      reliably distinguished on needle core biopsy from other lipomatous and vascular
      tumors of the breast. Tortuosity and proliferation of capillaries with at least 3
      interconnected capillary channels in 1 focus with associated fibrin thrombi
      constitute a very strong clue for the diagnosis of AL on a breast needle core
      biopsy. Definite diagnosis of cellular AL is not always feasible because of rare
      cases with mitotic activity and cellular atypia. Excision is often recommended
      for cellular AL.

PMID- 21087988
TI  - Multidimensional assessment of older people with asthma and COPD: clinical
      management and health status.
AB  - BACKGROUND: the diagnosis and management of obstructive airway diseases (OADs)
      such as asthma and chronic obstructive pulmonary disease (COPD) can be
      challenging in older people. OBJECTIVE: to assess the clinical, functional,
      biological and behavioural characteristics relevant to the management of older
      people with OAD. METHODS: a cross-sectional study was conducted in a tertiary
      teaching hospital. Older people (> 55 years) (n = 100) with an OAD underwent a
      multidimensional assessment (MDA) involving questionnaires, clinical assessments,
      physiological measurements and biomarkers. RESULTS: the assessment identified a
      mean (SD) of 11.3 (2.5) clinical management issues and 3.1 (1.8) comorbid
      conditions per participant. Common problems were: airways hyper-responsiveness
      (80%); airway inflammation (74%); activity limitation (74%) and systemic
      inflammation (60.5%). The number and type of issues were similar irrespective of
      a diagnosis of asthma or COPD (P = 0.2). The degree of health status impairment
      correlated significantly with the number of clinical management issues detected
      (r = 0.59; P < 0.0001). CONCLUSIONS: older people with OAD experience multiple
      clinical issues that adversely impact their health status. The number and type
      are similar irrespective of diagnosis. This MDA identifies significant clinical
      issues that may not be addressed in a diagnosis centred approach suggesting that
      a multidisciplinary approach is necessary when assessing and managing older
      people with OAD.

PMID- 21087989
TI  - Driving anxiety and fear in young older adults in New Zealand.
AB  - BACKGROUND: driving anxiety and fear can have a marked impact on mobility and
      independence, although there is no data on the prevalence of this problem, and
      specific information about the rate of driving anxiety and fear in older adults
      is unknown. METHODS: the present study examines the prevalence of self-reported
      driving anxiety and fear in a sample of 2,491 adults aged 55-72 from a
      longitudinal survey of health and ageing in New Zealand. RESULTS: most of the
      sample (90%) described themselves as drivers who drove daily or weekly. Around
      70% of the sample reported no driving anxiety or fear, yet 17-20% endorsed a mild
      and 4-6% rated a moderate to severe level of driving anxiety and fear. Women
      reported higher levels of anxiety and fear about driving than men, but there were
      no age differences. Those who reported some level of driving anxiety engaged
      various alternative modes of transport, and a small number (2.4%) reported that
      their driving anxiety had affected their usual activities or work for at least a
      day in the previous month. Duration of driving anxiety was highly variable, from
      relatively recent onset to being present for much of some participants'
      lifetimes. CONCLUSION: driving anxiety and fear may be a significant problem for
      some young older adults that is likely to affect their independence and mobility.
      Further research to clarify the content and nature of driving anxiety, pathways
      to driving anxiety and the effect of factors associated with ageing on driving
      anxiety is needed in order to better understand this experience for older adults
      and develop effective interventions.

PMID- 21087990
TI  - Hip fracture risk and subsequent mortality among Alzheimer's disease patients in
      the United Kingdom, 1988-2007.
AB  - BACKGROUND: hip fractures result in a significant burden to the patient, their
      caregivers and the health care system. Patients with Alzheimer's disease (AD)
      have a higher incidence of hip fracture compared with other older people without
      AD, although it is not clear if AD is an independent risk factor for hip
      fracture. METHODS: a retrospective cohort study was conducted using anonymised
      electronic medical records from primary care practices in the United Kingdom.
      Proportional hazards regression modelling with adjustment for potential
      confounders was used to evaluate AD as an independent risk factor for predicting
      hip fractures. RESULTS: the incidence of hip fracture among patients with and
      without AD was 17.4 (95% CI, 15.7-19.2) and 6.6 (95% CI, 5.8-7.6) per 1,000
      person years, respectively. Patients with AD had a hazard that was 3.2 (95% CI,
      2.4-4.2) times that of non-AD patients after controlling for potential
      confounders. AD patients who experienced a hip fracture also had an increased
      mortality rate compared with non-AD patients who experienced a hip fracture
      (hazard ratio = 1.5; 95% CI, 1.1-1.9). CONCLUSION: patients with AD and their
      caregivers should be advised on how to prevent hip fractures and more attention
      should be given to AD patients who are undergoing rehabilitation following a hip
      fracture.

PMID- 21087991
TI  - Cyber infrastructure for Fusarium: three integrated platforms supporting strain
      identification, phylogenetics, comparative genomics and knowledge sharing.
AB  - The fungal genus Fusarium includes many plant and/or animal pathogenic species
      and produces diverse toxins. Although accurate species identification is critical
      for managing such threats, it is difficult to identify Fusarium morphologically.
      Fortunately, extensive molecular phylogenetic studies, founded on well-preserved
      culture collections, have established a robust foundation for Fusarium
      classification. Genomes of four Fusarium species have been published with more
      being currently sequenced. The Cyber infrastructure for Fusarium (CiF;
      http://www.fusariumdb.org/) was built to support archiving and utilization of
      rapidly increasing data and knowledge and consists of Fusarium-ID, Fusarium
      Comparative Genomics Platform (FCGP) and Fusarium Community Platform (FCP). The
      Fusarium-ID archives phylogenetic marker sequences from most known species along
      with information associated with characterized isolates and supports strain
      identification and phylogenetic analyses. The FCGP currently archives five
      genomes from four species. Besides supporting genome browsing and analysis, the
      FCGP presents computed characteristics of multiple gene families and functional
      groups. The Cart/Favorite function allows users to collect sequences from
      Fusarium-ID and the FCGP and analyze them later using multiple tools without
      requiring repeated copying-and-pasting of sequences. The FCP is designed to serve
      as an online community forum for sharing and preserving accumulated experience
      and knowledge to support future research and education.

PMID- 21087992
TI  - CLIPZ: a database and analysis environment for experimentally determined binding
      sites of RNA-binding proteins.
AB  - The stability, localization and translation rate of mRNAs are regulated by a
      multitude of RNA-binding proteins (RBPs) that find their targets directly or with
      the help of guide RNAs. Among the experimental methods for mapping RBP binding
      sites, cross-linking and immunoprecipitation (CLIP) coupled with deep sequencing
      provides transcriptome-wide coverage as well as high resolution. However, partly
      due to their vast volume, the data that were so far generated in CLIP experiments
      have not been put in a form that enables fast and interactive exploration of
      binding sites. To address this need, we have developed the CLIPZ database and
      analysis environment. Binding site data for RBPs such as Argonaute 1-4, Insulin
      like growth factor II mRNA-binding protein 1-3, TNRC6 proteins A-C, Pumilio 2,
      Quaking and Polypyrimidine tract binding protein can be visualized at the level
      of the genome and of individual transcripts. Individual users can upload their
      own sequence data sets while being able to limit the access to these data to
      specific users, and analyses of the public and private data sets can be performed
      interactively. CLIPZ, available at http://www.clipz.unibas.ch, aims to provide an
      open access repository of information for post-transcriptional regulatory
      elements.

PMID- 21087993
TI  - Change of tRNA identity leads to a divergent orthogonal histidyl-tRNA
      synthetase/tRNAHis pair.
AB  - Mature tRNA(His) has at its 5'-terminus an extra guanylate, designated as G(-1).
      This is the major recognition element for histidyl-tRNA synthetase (HisRS) to
      permit acylation of tRNA(His) with histidine. However, it was reported that
      tRNA(His) of a subgroup of alpha-proteobacteria, including Caulobacter
      crescentus, lacks the critical G(-1) residue. Here we show that recombinant C.
      crescentus HisRS allowed complete histidylation of a C. crescentus tRNA(His)
      transcript (lacking G(-1)). The addition of G(-1) did not improve aminoacylation
      by C. crescentus HisRS. However, mutations in the tRNA(His) anticodon caused a
      drastic loss of in vitro histidylation, and mutations of bases A73 and U72 also
      reduced charging. Thus, the major recognition elements in C. crescentus tRNA(His)
      are the anticodon, the discriminator base and U72, which are recognized by the
      divergent (based on sequence similarity) C. crescentus HisRS. Transplantation of
      these recognition elements into an Escherichia coli tRNA(His) template, together
      with addition of base U20a, created a competent substrate for C. crescentus
      HisRS. These results illustrate how a conserved tRNA recognition pattern changed
      during evolution. The data also uncovered a divergent orthogonal HisRS/tRNA(His)
      pair.

PMID- 21087994
TI  - IUPHAR-DB: new receptors and tools for easy searching and visualization of
      pharmacological data.
AB  - The IUPHAR database is an established online reference resource for several
      important classes of human drug targets and related proteins. As well as
      providing recommended nomenclature, the database integrates information on the
      chemical, genetic, functional and pathophysiological properties of receptors and
      ion channels, curated and peer-reviewed from the biomedical literature by a
      network of experts. The database now includes information on 616 gene products
      from four superfamilies in human and rodent model organisms: G protein-coupled
      receptors, voltage- and ligand-gated ion channels and, in a recent update, 49
      nuclear hormone receptors (NHRs). New data types for NHRs include details on co
      regulators, DNA binding motifs, target genes and 3D structures. Other recent
      developments include curation of the chemical structures of approximately 2000
      ligand molecules, providing electronic descriptors, identifiers, link-outs and
      calculated molecular properties, all available via enhanced ligand pages. The
      interface now provides intelligent tools for the visualization and exploration of
      ligand structure-activity relationships and the structural diversity of compounds
      active at each target. The database is freely available at http://www.iuphar
      db.org.

PMID- 21087995
TI  - Laminin database: a tool to retrieve high-throughput and curated data for studies
      on laminins.
AB  - The Laminin(LM)-database, hosted at http://www.lm.lncc.br, is the first database
      focusing a non-collagenous extracellular matrix protein family, the LMs. Part of
      the knowledge available in this website is automatically retrieved, whereas a
      significant amount of information is curated and annotated, thus placing LM
      database beyond a simple repository of data. In its home page, an overview of the
      rationale for the database is seen and readers can access a tutorial to
      facilitate navigation in the website, which in turn is presented with tabs
      subdivided into LMs, receptors, extracellular binding and other related proteins.
      Each tab opens into a given LM or LM-related molecule, where the reader finds a
      series of further tabs for 'protein', 'gene structure', 'gene expression' and
      'tissue distribution' and 'therapy'. Data are separated as a function of species,
      comprising Homo sapiens, Mus musculus and Rattus novergicus. Furthermore, there
      is specific tab displaying the LM nomenclatures. In another tab, a direct link to
      PubMed, which can be then consulted in a specific way, in terms of the biological
      functions of each molecule, knockout animals and genetic diseases, immune
      response and lymphomas/leukemias. LM-database will hopefully be a relevant tool
      for retrieving information concerning LMs in health and disease, particularly
      regarding the hemopoietic system.

PMID- 21087996
TI  - Structural insight into the functional mechanism of Nep1/Emg1 N1-specific
      pseudouridine methyltransferase in ribosome biogenesis.
AB  - Nucleolar Essential Protein 1 (Nep1) is required for small subunit (SSU)
      ribosomal RNA (rRNA) maturation and is mutated in Bowen-Conradi Syndrome.
      Although yeast (Saccharomyces cerevisiae) Nep1 interacts with a consensus
      sequence found in three regions of SSU rRNA, the molecular details of the
      interaction are unknown. Nep1 is a SPOUT RNA methyltransferase, and can catalyze
      methylation at the N1 of pseudouridine. Nep1 is also involved in assembly of
      Rps19, an SSU ribosomal protein. Mutations in Nep1 that result in decreased
      methyl donor binding do not result in lethality, suggesting that enzymatic
      activity may not be required for function, and RNA binding may play a more
      important role. To study these interactions, the crystal structures of the scNep1
      dimer and its complexes with RNA were determined. The results demonstrate that
      Nep1 recognizes its RNA site via base-specific interactions and stabilizes a stem
      loop in the bound RNA. Furthermore, the RNA structure observed contradicts the
      predicted structures of the Nep1-binding sites within mature rRNA, suggesting
      that the Nep1 changes rRNA structure upon binding. Finally, a uridine base is
      bound in the active site of Nep1, positioned for a methyltransfer at the C5
      position, supporting its role as an N1-specific pseudouridine methyltransferase.

PMID- 21087997
TI  - CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double
      strand breaks in G1.
AB  - Topoisomerases class II (topoII) cleave and re-ligate the DNA double helix to
      allow the passage of an intact DNA strand through it. Chemotherapeutic drugs such
      as etoposide target topoII, interfere with the normal enzymatic cleavage/re
      ligation reaction and create a DNA double-strand break (DSB) with the enzyme
      covalently bound to the 5'-end of the DNA. Such DSBs are repaired by one of the
      two major DSB repair pathways, non-homologous end-joining (NHEJ) or homologous
      recombination. However, prior to repair, the covalently bound topoII needs to be
      removed from the DNA end, a process requiring the MRX complex and ctp1 in fission
      yeast. CtIP, the mammalian ortholog of ctp1, is known to promote homologous
      recombination by resecting DSB ends. Here, we show that human cells arrested in
      G0/G1 repair etoposide-induced DSBs by NHEJ and, surprisingly, require the MRN
      complex (the ortholog of MRX) and CtIP. CtIP's function for repairing etoposide
      induced DSBs by NHEJ in G0/G1 requires the Thr-847 but not the Ser-327
      phosphorylation site, both of which are needed for resection during HR. This
      finding establishes that CtIP promotes NHEJ of etoposide-induced DSBs during
      G0/G1 phase with an end-processing function that is distinct to its resection
      function.

PMID- 21087999
TI  - dictyBase update 2011: web 2.0 functionality and the initial steps towards a
      genome portal for the Amoebozoa.
AB  - dictyBase (http://www.dictybase.org), the model organism database for
      Dictyostelium, aims to provide the broad biomedical research community with well
      integrated, high quality data and tools for Dictyostelium discoideum and related
      species. dictyBase houses the complete genome sequence, ESTs, and the entire body
      of literature relevant to Dictyostelium. This information is curated to provide
      accurate gene models and functional annotations, with the goal of fully
      annotating the genome to provide a 'reference genome' in the Amoebozoa clade. We
      highlight several new features in the present update: (i) new annotations; (ii)
      improved interface with web 2.0 functionality; (iii) the initial steps towards a
      genome portal for the Amoebozoa; (iv) ortholog display; and (v) the complete
      integration of the Dicty Stock Center with dictyBase.

PMID- 21087998
TI  - 7SK small nuclear RNA directly affects HMGA1 function in transcription
      regulation.
AB  - Non-coding (nc) RNAs are increasingly recognized to play important regulatory
      roles in eukaryotic gene expression. The highly abundant and essential 7SK ncRNA
      has been shown to negatively regulate RNA Polymerase II transcription by
      inactivating the positive transcription elongation factor b (P-TEFb) in cellular
      and Tat-dependent HIV transcription. Here, we identify a more general, P-TEFb
      independent role of 7SK RNA in directly affecting the function of the
      architectural transcription factor and chromatin regulator HMGA1. An important
      regulatory role of 7SK RNA in HMGA1-dependent cell differentiation and
      proliferation regulation is uncovered with the identification of over 1500 7SK
      responsive HMGA1 target genes. Elevated HMGA1 expression is observed in nearly
      every type of cancer making the use of a 7SK substructure in the inhibition of
      HMGA1 activity, as pioneered here, potentially useful in therapy. The 7SK-HMGA1
      interaction not only adds an essential facet to the comprehension of
      transcriptional plasticity at the coupling of initiation and elongation, but also
      might provide a molecular link between HIV reprogramming of cellular gene
      expression-associated oncogenesis.

PMID- 21088001
TI  - Outcome of anatomic ganglionated plexi ablation to treat paroxysmal atrial
      fibrillation: a 3-year follow-up study.
AB  - AIMS: A new strategy for anatomically based ganglionated plexi (GP) ablation for
      the treatment of paroxysmal atrial fibrillation (AF) has been proposed recently.
      We aimed to assess the long-term outcome of patients undergoing anatomic GP
      ablation for paroxysmal AF, in comparison with circumferential pulmonary vein
      (PV) isolation. METHODS AND RESULTS: The study population consisted of 70
      patients (mean age 56.6 +/- 10.9 years; 41 males) with paroxysmal AF and no
      history of structural heart disease: 35 subjects underwent anatomic GP ablation,
      while 35 consecutive patients had circumferential PV isolation (CPVI) (control
      group). The groups were not different in demographic and clinical parameters.
      Anatomic GP ablation required more ablation points (85.6 +/- 5.5 vs. 74.4 +/-
      6.2, P < 0.05) and equal duration of total procedure and fluoroscopy times.
      During a mean follow-up period of 36.3 +/- 2.3 months, freedom from any atrial
      tachyarrhythmia without antiarrhythmics was achieved in 34.3% patients after
      anatomic GP ablation and 65.7% patients after CPVI (log-rank test P = 0.008).
      Early arrhythmia recurrences and anatomic GP ablation were independent predictors
      of late recurrence [HR 6.44 (CI 95%; 3.14-13.18; P < 0.001) and HR 2.08 (CI 95%;
      1.03-4.22; P = 0.04), respectively]. Six patients in the group of GP ablation
      underwent subsequent CPVI, plus peri-mitral flutter ablation in two of them, with
      no further arrhythmia episodes in five patients. CONCLUSION: Anatomic GP ablation
      yields a significantly lower success rate over the long-term follow-up period,
      when compared with CPVI. Recurrences include AF and macro re-entrant atrial
      tachycardias.

PMID- 21088002
TI  - The history of diagnosing carotid sinus hypersensitivity: why are the current
      criteria too sensitive?
AB  - The carotid sinus syndrome and carotid sinus hypersensitivity (CSH) are closely
      related disorders. The first is characterized by syncope triggered by
      manipulation of the carotid sinus in daily life (e.g. shaving). According to the
      current European Society of Cardiology guidelines, CSH is diagnosed when carotid
      sinus massage elicits >=3 s asystole, a fall in systolic blood pressure of >=50
      mmHg, or both, with symptoms. The question is, however, whether symptoms can be
      expected when these criteria are met. Although they are widely accepted, we will
      show that their basis is primarily in arbitrary clinical observations and that in
      the original publications the link between classification and clinical symptoms
      was often dubious. The current criteria for CSH are thus too sensitive,
      explaining the reported high prevalence of CSH in the general older population.
      The review will conclude with suggesting a stricter set of criteria for CSH that
      should be evaluated in future studies.

PMID- 21088003
TI  - Transseptal puncture in situs inversus totalis using a conventional fluoroscopic
      approach.
AB  - Situs inversus totalis (SIT) is a congenital disorder characterized by mirror
      reversal of the thoracic and abdominal organs. The underlying cardiovascular
      malpositions complicate transseptal catheterization. In the present report, we
      present the case of a patient with SIT, where access in the morphologic left
      atrium was gained with conventional fluoroscopic approach without the use of
      intracardiac imaging modalities.

PMID- 21088000
TI  - Epigenetic control of a VDR-governed feed-forward loop that regulates
      p21(waf1/cip1) expression and function in non-malignant prostate cells.
AB  - In non-malignant RWPE-1 prostate epithelial cells signaling by the nuclear
      receptor Vitamin D Receptor (VDR, NR1I1) induces cell cycle arrest through
      targets including CDKN1A (encodes p21((waf1/cip1))). VDR dynamically induced
      individual histone modification patterns at three VDR binding sites (R1, 2, 3) on
      the CDKN1A promoter. The magnitude of these modifications was specific to each
      phase of the cell cycle. For example, H3K9ac enrichment occurred rapidly only at
      R2, whereas parallel accumulation of H3K27me3 occurred at R1; these events were
      significantly enriched in G(1) and S phase cells, respectively. The epigenetic
      events appeared to allow VDR actions to combine with p53 to enhance
      p21((waf1/cip1)) activation further. In parallel, VDR binding to the MCM7 gene
      induced H3K9ac enrichment associated with rapid mRNA up-regulation to generate
      miR-106b and consequently regulate p21((waf1/cip1)) expression. We conclude that
      VDR binding site- and promoter-specific patterns of histone modifications combine
      with miRNA co-regulation to form a VDR-regulated feed-forward loop to control
      p21((waf1/cip1)) expression and cell cycle arrest. Dissection of this feed
      forward loop in a non-malignant prostate cell system illuminates mechanisms of
      sensitivity and therefore possible resistance in prostate and other VDR
      responsive cancers.

PMID- 21088004
TI  - An improved algorithm for intraoperative registration of computed tomographic
      left atrial images.
AB  - AIMS: Although anatomically accurate and highly detailed, preoperative computed
      tomographic (CT) images of the left atrium (LA) are of limited utility for
      guiding catheter navigation, in part because of changes in LA shape which occur
      between preoperative and intraoperative settings. Such changes may produce errors
      in spatial juxtaposition, or 'registration', of the CT image to the
      intraoperative environment. The goal of this study was to assess a new algorithm
      for CT image registration. METHODS AND RESULTS: In each of 10 patients, CT images
      were registered using LA endocardial points derived from intraoperative
      intracardiac echocardiography (CartoSound, Biosense). Two registration algorithms
      were compared: (i) CartoMerge (Biosense), a 'rigid' algorithm in which the CT
      image was not malleable; (ii) ImageMorph, a non-rigid algorithm in which CT image
      was malleable and was altered so as to more precisely fit the intraoperative
      point locations. There were no significant differences in LA volume or pulmonary
      vein antral dimensions on CT images after registration using CartoMerge vs.
      ImageMorph. Shape changes induced by ImageMorph were not concentrated in any one
      LA region. Registration quality was significantly better using ImageMorph, as was
      mock circumferential ablation accuracy. CONCLUSION: The potential for improved CT
      image-guided ablation accuracy using ImageMorph calls for further study to
      discern whether this algorithm yields tangible procedural and clinical benefits
      relative to currently available algorithms.

PMID- 21088005
TI  - Drug-eluting stents for the treatment of pulmonary vein stenosis after atrial
      fibrillation ablation.
AB  - AIMS: Pulmonary vein (PV) stenosis (PVS) is a complication of radiofrequency PV
      isolation (PVI). Reported restenosis rates after balloon dilatation and bare
      metal stent implantation are high. Drug-eluting stent implantation (DES) has not
      been reported in the setting of PVS. METHODS AND RESULTS: Patients suspected of
      having PVS after PVI based on clinical symptoms and transesophageal
      echocardiography (TEE) follow-up (FU) were referred for PV DES. One or more
      branches of the affected PV as documented by angiography were stented (paclitaxel
      or zotarolimus DES). Follow-up consisted of repeat PV angiography and TEE. Over a
      period of 2 years, five patients were treated with a total of eight DES. A
      paclitaxel DES was used in seven of eight implants. Mean FU was 12 +/- 14 months
      during which all patients remained asymptomatic. Transesophageal echocardiography
      Doppler maximal flow velocity (V(max)) of the affected PVs rose from 58 +/- 6
      cm/s pre-PVI to 207 +/- 20 cm/s pre-DES (+358%, P < 0.0001). After DES, V(max)
      decreased acutely with 86 +/- 15 cm/s (-58%, P < 0.01). During FU, V(max)
      remained stable in three patients and increased moderately in one. Angiography at
      3 months confirmed absence of restenosis in the first three patients and moderate
      (40%) restenosis in one patient. In one patient, an increase of V(max) back to
      pre-DES values correlated with a 65% peri-stent stenosis, treated with a redo
      DES. In total, after seven primary DES only one (asymptomatic) proximal margin
      restenosis required re-stenting. CONCLUSION: Initial experience with DES for PV
      stenosis suggests an excellent stent patency rate. Transesophageal
      echocardiography Doppler measurements provide a viable way of monitoring stent
      patency.

PMID- 21088006
TI  - The impact of social and cultural capital variables on parental rating of child
      health in Australia.
AB  - The aim of this paper is to study the effects of factors broadly captured under
      the rubric of parental social and cultural capital on child health. The setting
      was 11 disadvantaged communities in Victoria, Australia during the conduct and
      evaluation of Best Start, an early childhood initiative of the Victorian State
      Government. Questionnaires were sent to parents of 3-year-old children in 2004
      and 2006. The principal dependent variable was parental global rating of their
      child's health. Social capital variables focussed, for example, on community
      support for parent's child rearing practices. Cultural capital variables
      focussed, for example, on parent's reading to their child. Socio-economic status
      and other potential confounding variables were also measured. Stepwise
      multivariable logistic regression was used. There were consistent independent
      effects for the cultural capital variables-'Age started reading to the child' and
      'Confident being a good parent', and only one of a number of social capital
      variables-'Community support for childrearing' as well as for some other
      variables particularly that 'Child had a chronic health/medical condition'.
      Dichotomizing parent's global ratings of their child's health differently had
      some effects on results. Cultural capital and, to a lesser extent, social capital
      variables were associated with parent's rating of the child's health. It is now
      timely to conduct and evaluate programs aimed at improving parents' cultural
      capital. Better measures or inventories of parent's cultural capital will be
      essential for this.

PMID- 21088007
TI  - Health-promoting organization and organizational effectiveness of health
      promotion in hospitals: a national cross-sectional survey in Taiwan.
AB  - To assess the organizational health-promotion (HP) status and its effect on the
      organizational effectiveness of HP in a national cross-sectional survey of all
      hospitals above the local community hospital level in Taiwan's hospitals,
      questionnaires were sent to 474 hospitals, of which 162 (34.18%) hospitals
      returned them and were rendered valid. The results of the organizational HP
      status reveal that the standardized overall score achieved is 76.26, suggesting
      that there is considerable room for improvement. The results of correlation
      analysis partially support the proposition of this study, suggesting that the
      higher the organizational HP status, the better the self-evaluated overall
      organizational and administrative effectiveness of its HP. When hierarchical
      multiple regression was performed, support for ownership (private hospitals),
      hospital accreditation grades (academic medical centers) and overall score of the
      Organizational Health of Hospital Assessment Scale were significant predicators
      of self-evaluated overall organizational effectiveness (F = 11.097, p < 0.01,
      R(2) = 0.369). Moreover, drafted annually, HP policies and plans and the number
      of staff HP training activities were found to partially mediate the relation
      between the organizational HP status, hospital characteristics and self-evaluated
      overall organizational effectiveness. The results contribute to clarify the
      conception of health-promoting hospital organizations and to identify a number of
      dimensions of health-promoting organizations related to the organizational
      effectiveness of HP in hospitals, which could allow hospitals to establish a
      healthier organization and more effective HP programs. This study also supplies
      the research field with important data and insights that can be used in future
      research.

PMID- 21088008
TI  - Species delimitation under the general lineage concept: an empirical example
      using wild North American hops (Cannabaceae: Humulus lupulus).
AB  - There is an emerging consensus that the intent of most species concepts is to
      identify evolutionarily distinct lineages. However, the criteria used to identify
      lineages differ among concepts depending on the perceived importance of various
      attributes of evolving populations. We have examined five different species
      criteria to ask whether the three taxonomic varieties of Humulus lupulus (hops)
      native to North America are distinct lineages. Three criteria (monophyly, absence
      of genetic intermediates, and diagnosability) focus on evolutionary patterns and
      two (intrinsic reproductive isolation and niche specialization) consider
      evolutionary processes. Phylogenetic analysis of amplified fragment length
      polymorphism (AFLP) data under a relaxed molecular clock, a stochastic Dollo
      substitution model, and parsimony identified all varieties as monophyletic, thus
      they satisfy the monophyly criterion for species delimitation. Principal
      coordinate analysis and a Bayesian assignment procedure revealed deep genetic
      subdivisions and little admixture between varieties, indicating an absence of
      genetic intermediates and compliance with the genotypic cluster species
      criterion. Diagnostic morphological and AFLP characters were found for all
      varieties, thus they meet the diagnosability criterion. Natural history
      information suggests that reproductive isolating barriers may have evolved in
      var. pubescens, potentially qualifying it as a species under a criterion of
      intrinsic reproductive isolation. Environmental niche modeling showed that the
      preferred habitat of var. neomexicanus is climatically unique, suggesting niche
      specialization and thus compliance with an ecological species criterion.
      Isolation by distance coupled with imperfect sampling can lead to erroneous
      lineage identification using some species criteria. Compliance with complementary
      pattern- and process-oriented criteria provides powerful corroboration for a
      species hypothesis and mitigates the necessity for comprehensive sampling of the
      entire species range, a practical impossibility in many systems. We hypothesize
      that var. pubescens maintains its genetic identity, despite substantial niche
      overlap with var. lupuloides, via the evolution of partial reproductive isolating
      mechanisms. Variety neomexicanus, conversely, will likely persist as a distinct
      lineage, regardless of limited gene flow with vars. lupuloides and pubescens
      because of ecological isolation--adaptation to the unique conditions of the Rocky
      Mountain cordillera. Thus, we support recognition of vars. neomexicanus and
      pubescens as species, but delay making a recommendation for var. lupuloides until
      sampling of genetic variation is complete or a stable biological process can be
      identified to explain its observed genetic divergence.

PMID- 21088009
TI  - The accuracy of species tree estimation under simulation: a comparison of
      methods.
AB  - Numerous simulation studies have investigated the accuracy of phylogenetic
      inference of gene trees under maximum parsimony, maximum likelihood, and Bayesian
      techniques. The relative accuracy of species tree inference methods under
      simulation has received less study. The number of analytical techniques available
      for inferring species trees is increasing rapidly, and in this paper, we compare
      the performance of several species tree inference techniques at estimating recent
      species divergences using computer simulation. Simulating gene trees within
      species trees of different shapes and with varying tree lengths (T) and
      population sizes (), and evolving sequences on those gene trees, allows us to
      determine how phylogenetic accuracy changes in relation to different levels of
      deep coalescence and phylogenetic signal. When the probability of discordance
      between the gene trees and the species tree is high (i.e., T is small and/or is
      large), Bayesian species tree inference using the multispecies coalescent (BEST)
      outperforms other methods. The performance of all methods improves as the total
      length of the species tree is increased, which reflects the combined benefits of
      decreasing the probability of discordance between species trees and gene trees
      and gaining more accurate estimates for gene trees. Decreasing the probability of
      deep coalescences by reducing also leads to accuracy gains for most methods.
      Increasing the number of loci from 10 to 100 improves accuracy under difficult
      demographic scenarios (i.e., coalescent units <= 4N(e)), but 10 loci are adequate
      for estimating the correct species tree in cases where deep coalescence is
      limited or absent. In general, the correlation between the phylogenetic accuracy
      and the posterior probability values obtained from BEST is high, although
      posterior probabilities are overestimated when the prior distribution for is
      misspecified.

PMID- 21088010
TI  - Chronic vagal nerve stimulation for the treatment of human heart failure:
      progress in translating a vision into reality.

PMID- 21088012
TI  - How health insurance design affects access to care and costs, by income, in
      eleven countries.
AB  - This 2010 survey examines the insurance-related experiences of adults in
      Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden,
      Switzerland, the United States, and the United Kingdom. The countries all have
      different systems of coverage, ranging from public systems to hybrid systems of
      public and private insurance, and with varying levels of cost sharing. Overall,
      the study found significant differences in access, cost burdens, and problems
      with health insurance that are associated with insurance design. US adults were
      the most likely to incur high medical expenses, even when insured, and to spend
      time on insurance paperwork and disputes or to have payments denied. Germans
      reported spending time on paperwork at rates similar to US rates but were well
      protected against out-of-pocket spending. Swiss out-of-pocket spending was high,
      yet few Swiss had access concerns or problems paying bills. For US adults,
      comprehensive health reforms could lead to improvements in many of these areas,
      including reducing differences by income observed in the study.

PMID- 21088011
TI  - Genome-wide association study identifies a new locus for coronary artery disease
      on chromosome 10p11.23.
AB  - AIMS: Recent genome-wide association (GWA) studies identified 10 chromosomal loci
      for coronary artery disease (CAD) or myocardial infarction (MI). However, these
      loci explain only a small proportion of the genetic variability of these
      pertinent diseases. We sought to identify additional CAD/MI loci by applying a
      three-stage approach. METHODS AND RESULTS: We genotyped n = 1157 MI cases and n =
      1748 controls from a population-based study population [German MI Family Study
      (GerMIFS) III (KORA)] with genome-wide SNP arrays. At this first stage, n = 462
      SNPs showed association with MI at P<1 * 10(-3) in two-sided logistic regression.
      In a second stage, 415 of these SNPs were evaluated in silico in two independent
      GWA samples, the GerMIFS I (875 cases/1644 controls) and GerMIFS II (1222
      cases/1298 controls). Nine SNPs, representing three regions, displayed consistent
      replication in this in silico analysis (P<0.05 for each GWA sample): five SNPs at
      9p21.3, a well-known CAD/MI locus, two SNPs at 10p11.21, and two SNPs at 2p24.3.
      Wet-lab replication, i.e. the third stage, of SNP rs3739998 (representing the
      novel locus at 10p11.21, p.S1002T in the KIAA1462 gene) in additional 5790 cases
      and 5302 controls confirmed the association (P=9.54 * 10(-4)), but not for the
      2p24.3 locus. The combined P-value across all stages for SNP rs3739998 is P=1.27
      * 10(-11) [odds ratio (OR) = 1.15 (1.11-1.20)]. CONCLUSION: Analysis of a GWA
      study followed by in silico and wet-lab replication steps identified the KIAA1462
      gene, encoding a yet uncharacterized protein, on chromosome 10p11.23 with genome
      wide significant association for CAD/MI. Further studies are needed to
      characterize the functional role of this locus in the aetiology of these
      diseases.

PMID- 21088013
TI  - A novel embryo identification system by direct tagging of mouse embryos using
      silicon-based barcodes.
AB  - BACKGROUND: Measures to prevent assisted reproductive technologies (ART) mix-ups,
      such as labeling of all labware and double-witnessing protocols, are currently in
      place in fertility clinics worldwide. Technological solutions for electronic
      witnessing are also being developed. However, none of these solutions eliminate
      the risk of identification errors, because gametes and embryos must be
      transferred between containers several times during an ART cycle. Thus, the
      objective of this study was to provide a proof of concept for a direct embryo
      labeling system using silicon-based barcodes. METHODS: Three different types of
      silicon-based barcodes (A, B and C) were designed and manufactured, and
      microinjected into the perivitelline space of mouse pronuclear embryos (one to
      four barcodes per embryo). Embryos were cultured in vitro until the blastocyst
      stage, and rates of embryo development, retention of the barcodes in the
      perivitelline space and embryo identification were assessed every 24 h. Release
      of the barcodes after embryo hatching was also determined. Finally, embryos
      microinjected with barcodes were frozen and thawed at the 2-cell stage to test
      the validity of the system after cryopreservation. RESULTS: Barcodes present in
      the perivitelline space, independently of their type and number, did not affect
      embryo development rates. The majority of embryos (>90%) retained at least one of
      the microinjected barcodes in their perivitelline space up to the blastocyst
      stage. Increasing the number of barcodes per embryo resulted in a significant
      increase in embryo identification rates, but a significant decrease in the
      barcode release rates after embryo hatching. The highest rates of successful
      embryo identification (97%) were achieved with the microinjection of four type C
      barcodes, and were not affected by cryopreservation. CONCLUSIONS: Our results
      demonstrate the feasibility of a direct embryo labeling system and constitute the
      starting point in the development of such systems.

PMID- 21088014
TI  - Characteristics of men willing to act as sperm donors in the context of identity
      release legislation.
AB  - BACKGROUND: Although ongoing legislative changes are important to protect the
      rights of all involved in assisted reproductive technologies, it cannot be
      guaranteed that legislation will ensure the successful operation of reproductive
      health clinics, as is indicated by ongoing reports of a dearth of donor sperm in
      clinics in some countries. METHODS: Data were 1428 profiles taken from a website
      that aims to facilitate relationships between those seeking donor sperm and men
      willing to donate their sperm. Data were coded as three independent variables:
      age, relationship status and country, and four dependent variables: motivation to
      donate, willingness to be identified, willingness to be involved with children
      conceived of donations and beliefs about who should determine the level of
      involvement. RESULTS: Non-parametric testing indicated that men aged under 26 or
      over 46, and who were either single or in a same-sex relationship, were most
      likely to be willing to be identified to children (P< 0.05), and to desire
      involvement with children (P< 0.01). A significant proportion of men aged between
      26 and 46 years of age (P< 0.001) were motivated by a desire to procreate and
      were unwilling to be identified, as were a significant number of men in opposite
      sex relationships (P< 0.001). CONCLUSIONS: Although limited by its reliance upon
      a sample constituted by men living in western countries who completed a self
      report profile and who had not received counselling about their potential role as
      donors, this study draws attention to the potential impact of age and sexual
      orientation upon intentions to donate.

PMID- 21088015
TI  - Assessment of acrosome and nuclear abnormalities in human spermatozoa with large
      vacuoles.
AB  - BACKGROUND: Spermatozoa with large vacuoles (SLV) may have a negative impact on
      embryo development. The origin of these vacuoles is unknown. We evaluated
      acrosome and nucleus alterations in isolated SLV, versus unselected spermatozoa.
      METHODS: We studied 20 patients with teratozoospermia. Spermatozoa from the
      native semen sample and spermatozoa presenting a vacuole occupying >13.0% total
      head area, isolated under high magnification (*6600), were assessed. Confocal and
      transmission electron microscope evaluations were performed on SLV and native
      sperm, respectively. Acrosome morphology and DNA fragmentation were analysed
      using proacrosin immunolabelling (monoclonal antibody 4D4) and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Chromatin
      condensation was evaluated with aniline blue staining. Sperm aneuploidy was
      assessed using fluorescence in situ hybridization. RESULTS: SLV represented 38.0
      +/- 5.10% of motile spermatozoa obtained after gradient density centrifugation.
      Vacuoles were mainly in the anterior and median sperm head (45.7 +/- 2.90 and
      46.1 +/- 3.00%, respectively). Abnormal acrosomes were increased in SLV compared
      with unselected spermatozoa (77.8 +/- 2.49 versus 70.6 +/- 2.62%; P = 0.014).
      Microscopic observations showed an exclusively nuclear localization of large
      vacuoles. Complete DNA fragmentation was higher in native spermatozoa (P <
      0.0001) than SLV, while chromatin condensation was altered in SLV (P < 0.0001).
      Aneuploidy and diploidy rates were increased in SLV (P < 0.0001). CONCLUSIONS:
      Sperm vacuoles were exclusively nuclear. In our selected teratozoospermic
      population, aneuploidy and chromatin condensation defects were the main
      alterations observed in SLV. Based on results from this small sample of
      spermatozoa, we propose a global impairment of the spermatogenesis process as a
      common origin of the morphological alterations.

PMID- 21088016
TI  - High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and
      a reduced risk of abdominal obesity in women with polycystic ovary syndrome.
AB  - BACKGROUND: Women with polycystic ovary syndrome (PCOS) are known to have high
      prevalence of acne and elevated androgen levels. The current study aims to
      determine if dehydroepiandrosterone sulfate (DHEAS) level is associated with the
      presence of acne and reduced risk of abdominal obesity in women with PCOS, after
      considering the concurrent high testosterone level and insulin resistance (IR).
      METHODS: Three hundred and eighteen untreated consecutive Taiwanese women with
      PCOS were enrolled. Phenotypic hyperandrogenism was recorded, and BMI, waist
      circumference, waist-to-hip ratio, lipid profiles, fasting glucose and insulin
      levels and hormone profiles were measured. RESULTS: Women with acne were younger,
      had higher serum DHEAS levels (6.01 +/- 3.45 versus 4.87 +/- 2.49 MUmol/l, P =
      0.002) and a lower BMI (P = 0.0006), but comparable serum testosterone levels, in
      comparison with women without acne. The aggravating effect of elevated DHEAS on
      the risk of acne (odds ratio = 2.15, 95% confidence interval: 1.25-3.68, P =
      0.005 for DHEAS cut-off of 6.68 MUmol/l) still exited after adjustment for age
      and BMI. The DHEAS level was positively correlated with the testosterone level,
      but inversely related to waist circumference, waist-to-hip ratio, BMI, IR index,
      low-density lipoprotein-cholesterol and triglycerides. Women with PCOS in the
      highest quartile of DHEAS had the lowest risk of abdominal obesity after
      adjustment for age, IR, dyslipidemia, testosterone and estradiol levels.
      CONCLUSIONS: Our results demonstrated the high serum DHEAS in women with PCOS was
      associated with the presence of acne and a significantly reduced risk of
      abdominal obesity, independent of serum testosterone concentration and IR.

PMID- 21088017
TI  - Malignancies among women who gave birth after in vitro fertilization.
AB  - BACKGROUND: Relatively few studies published to date have investigated IVF and
      cancer risk. In this study we compared the occurrence of cancer in women who gave
      birth after IVF with all other women who gave birth in the study period. METHODS:
      All women who were treated with IVF and gave birth during the years 1982-2006 in
      Sweden were identified from all IVF clinics, and the occurrence of cancer in
      these women was identified by linkage with the nationwide Swedish cancer
      register. Comparison was made with Mantel-Haenszel odds ratios (ORs), adjusting
      for year of delivery and maternal age, parity and smoking. Cancer before IVF was
      only studied in first parity women. Specific cancer forms were also studied.
      RESULTS: Among 24058 women who had been treated with IVF, 1279 appeared in the
      cancer register. The total number of women studied in the population was 1 394
      061, and 95 775 of these were registered in the cancer register. The risk for
      cancer before IVF was increased [OR 1.37, 95% confidence interval (CI) 1.27-1.48]
      and was especially high for ovarian cancer (3.93). The risk for cancer after IVF
      was significantly lower (OR 0.74, 95% CI 0.67-0.82), mainly due to a lower than
      expected risk for breast and cervical cancer. The risk for ovarian cancer was
      increased but lower than the risk before IVF (2.13). CONCLUSIONS: Cancer or
      cancer treatment may increase the risk for infertility leading to IVF. After IVF,
      in most cases with treatment with fertility hormones, a significantly low cancer
      risk was found. Ovarian cancer showed an increased risk, although lower than
      before IVF. One possible reason is ovarian pathology causing both infertility and
      an increased cancer risk.

PMID- 21088018
TI  - The capacity of hysterosalpingography and laparoscopy to predict natural
      conception.
AB  - BACKGROUND: Laparoscopy has been claimed to be superior to hysterosalpingography
      (HSG) in predicting fertility. Whether this conclusion is applicable to a general
      subfertile population can be questioned as data in support of this claim were
      collected in third line centres. The aim of this study was to assess the
      prognostic capacity of HSG and laparoscopy in a general subfertile population.
      METHODS: In 38 centres, we prospectively studied a cohort of patients referred
      for subfertility between 2002 and 2004, who underwent HSG and/or laparoscopy as
      part of their subfertility work-up. Follow-up started immediately after tubal
      testing and ended 12 months thereafter. Time to pregnancy was censored at the of
      date last contact, when the woman was not pregnant or at the start of treatment.
      Kaplan-Meier curves for the occurrence of spontaneous intrauterine pregnancy were
      constructed for patients without tubal pathology, for those with unilateral tubal
      pathology and for patients with bilateral tubal pathology at HSG or laparoscopy.
      Multivariable Cox regression analysis was used to calculate fecundity rate ratios
      (FRRs) to express associations between tubal pathology and the occurrence of an
      intrauterine pregnancy. RESULTS: Of the 3301 included patients, 2043 underwent
      HSG only, 747 underwent diagnostic laparoscopy only and 511 underwent both. At
      HSG, 322 (13%) patients showed unilateral tubal pathology and 135 (5%) showed
      bilateral tubal pathology. At laparoscopy, 167 (13%) showed unilateral tubal
      pathology and 215 (17%) showed bilateral tubal pathology. Multivariable analysis
      resulted in FRRs of 0.81 [95% confidence interval (CI): 0.59-1.1] for unilateral,
      and 0.28 (95% CI: 0.13-0.59) for bilateral, tubal pathology at HSG. The FRRs at
      laparoscopy were 0.85 (95% CI: 0.47-1.52) for unilateral, and 0.24 (95% CI: 0.11
      0.54) for bilateral, tubal pathology. CONCLUSIONS: Patients with unilateral tubal
      pathology at HSG and laparoscopy had a moderate reduction in pregnancy chances,
      whereas those with bilateral tubal pathology at HSG and laparoscopy had a severe
      reduction in pregnancy chances. This reduction was similar for HSG and
      laparoscopy, suggesting that HSG and laparoscopy have a comparable predictive
      capacity for natural conception.

PMID- 21088020
TI  - Effect of overexpression of small non-coding DsrA RNA on multidrug efflux in
      Escherichia coli.
AB  - OBJECTIVES: Several putative and proven drug efflux pumps are present in
      Escherichia coli. Because many such efflux pumps have overlapping substrate
      spectra, it is intriguing that bacteria, with their economically organized
      genomes, harbour such large sets of multidrug efflux genes. To understand how
      bacteria utilize these multiple efflux pumps, it is important to elucidate the
      process of pump expression regulation. The aim of this study was to determine a
      regulator of the multidrug efflux pump in this organism. METHODS: We screened a
      genomic library of E. coli for genes that decreased drug susceptibility in this
      organism. The library was developed from the chromosomal DNA of the MG1655
      strain, and then the recombinant plasmids were transformed into an acrB-deleted
      strain. Transformants were screened for resistance to various antibiotics
      including oxacillin. RESULTS: We found that the multidrug susceptibilities of the
      acrB-deleted strain were decreased by the overexpression of small non-coding DsrA
      RNA as well as by the overexpression of known regulators of multidrug efflux
      pumps. Plasmids carrying the dsrA gene conferred resistance to oxacillin,
      cloxacillin, erythromycin, rhodamine 6G and novobiocin. DsrA decreased the
      accumulation of ethidium bromide in E. coli cells. Furthermore, expression of
      mdtE was significantly increased by dsrA overexpression, and the decreased
      multidrug susceptibilities modulated by DsrA were dependent on the MdtEF efflux
      pump. CONCLUSIONS: These results indicate that DsrA modulates multidrug efflux
      through activation of genes encoding the MdtEF pump in E. coli.

PMID- 21088019
TI  - Changing carbapenemase gene pattern in an epidemic multidrug-resistant
      Acinetobacter baumannii lineage causing multiple outbreaks in central Italy.
AB  - OBJECTIVES: infections caused by multidrug-resistant (MDR) Acinetobacter
      baumannii are a challenging problem worldwide. Here, the molecular epidemiology
      and the genetic basis of antibiotic resistance in 111 MDR A. baumannii strains
      isolated from June 2005 to March 2009 from infected patients in 10 intensive care
      units (ICUs) in central Italy were investigated. METHODS: epidemiological typing
      was performed by random amplification of polymorphic DNA, PCR-based sequence
      grouping and macrorestriction analysis. MICs of antibiotics were determined by
      the broth microdilution method. Genes for OXA carbapenemases, metallo-beta
      lactamases and the CarO porin were searched for by PCR. RESULTS: molecular
      genotyping identified one predominant A. baumannii lineage, related to the
      international clonal lineage II, accounting for 95.6% of isolates. Isolates
      referable to this lineage were recovered from all ICUs surveyed and were
      resistant to nearly all classes of antimicrobials, with the exception of
      tigecycline and colistin. A high percentage (60.5%) of A. baumannii isolates
      showed elevated resistance to imipenem (MICs >=  128 mg/L), concomitant with
      resistance to meropenem. Carbapenem resistance was associated with the presence
      of either bla(OXA-58)-like (22.8%) or bla(OXA-23)-like (71.1%) carbapenemase
      genes. Molecular typing showed that the epidemic lineage encoding OXA-23 emerged
      in 2007 and displaced a genetically related clone encoding OXA-58 that had been
      responsible for previous ICU outbreaks in the same region. CONCLUSIONS: emergence
      of the OXA-23 epidemic lineage could result from selective advantage conferred by
      the bla(OXA-23)-like determinant, which provides increased resistance to
      carbapenems.

PMID- 21088021
TI  - Intercomparison exercise within a distributed-dosimetry network.
AB  - The results of an intercomparison exercise within the US Navy dosimetric network
      (USN-DN) are presented and discussed. The USN-DN uses a commercially available
      LiF:Mg,Cu,P thermoluminescent dosemeter (TLD) model Harshaw 8840/8841 and TLD
      reader model Harshaw 8800 manufactured by Thermo Fisher Scientific. The USN-DN
      consists of a single calibration facility and 16 satellite dosimetry reading
      facilities throughout the world with ~ 40 model 8800 TLD readers and in excess of
      350 000 TLD cards in circulation. The Naval Dosimetry Center (NDC) is the primary
      calibration site responsible for the distribution and calibration of all TLD
      cards and their associated holders. In turn, each satellite facility is assigned
      a subpopulation of cards, which are utilised for servicing their local customers.
      Consistency of the NDC calibration of 150 dosemeters (calibrated at NDC) and 27
      locally calibrated remote readers was evaluated in the framework of this
      intercomparison. Accuracy of TLDs' calibration, performed at the NDC, was found
      to be <3 % throughout the entire network. Accuracy of the readers' calibration,
      performed with the NDC issued calibration dosemeters at remote sites, was found
      to be better than 4 % for most readers. The worst performance was found for
      reader Channel 3, which is calibrated using the thinnest chip of the Harshaw
      8840/8841 dosemeter. The loss of sensitivity of this chip may be caused by time
      temperature profile that has been designed for all four chips without
      consideration of chip thickness.

PMID- 21088022
TI  - Leprosy: down but not out.
AB  - Leprosy is a chronic disabling disease and there are areas of high endemicity in
      India. Case findings and management strategies suffer a setback when disease
      manifestations are not picked up in time by health-care providers. This article
      attempts to estimate the annual incidents of leprosy and to study the confounding
      factors which may potentially cause delays in diagnosis in an office-based,
      tertiary health-care setting.

PMID- 21088023
TI  - Five-minute Giemsa stain for rapid detection of malaria parasites in blood
      smears.
AB  - The Giemsa stain is used as the gold standard for the diagnosis of malaria on
      blood smears. The classical staining procedure requires between 30 and 45 min. We
      modified the Giemsa stain and reduced the staining time to 5 min without any loss
      of quality.

PMID- 21088025
TI  - SAMStat: monitoring biases in next generation sequencing data.
AB  - MOTIVATION: The sequence alignment/map format (SAM) is a commonly used format to
      store the alignments between millions of short reads and a reference genome.
      Often certain positions within the reads are inherently more likely to contain
      errors due to the protocols used to prepare the samples. Such biases can have
      adverse effects on both mapping rate and accuracy. To understand the relationship
      between potential protocol biases and poor mapping we wrote SAMstat, a simple C
      program plotting nucleotide overrepresentation and other statistics in mapped and
      unmapped reads in a concise html page. Collecting such statistics also makes it
      easy to highlight problems in the data processing and enables non-experts to
      track data quality over time. RESULTS: We demonstrate that studying sequence
      features in mapped data can be used to identify biases particular to one
      sequencing protocol. Once identified, such biases can be considered in the
      downstream analysis or even be removed by read trimming or filtering techniques.
      AVAILABILITY: SAMStat is open source and freely available as a C program running
      on all Unix-compatible platforms. The source code is available from
      http://samstat.sourceforge.net. CONTACT: timolassmann@gmail.com.

PMID- 21088026
TI  - Scoring-and-unfolding trimmed tree assembler: concepts, constructs and
      comparisons.
AB  - MOTIVATION: Mired by its connection to a well-known -complete combinatorial
      optimization problem-namely, the Shortest Common Superstring Problem (SCSP)
      historically, the whole-genome sequence assembly (WGSA) problem has been assumed
      to be amenable only to greedy and heuristic methods. By placing efficiency as
      their first priority, these methods opted to rely only on local searches, and are
      thus inherently approximate, ambiguous or error prone, especially, for genomes
      with complex structures. Furthermore, since choice of the best heuristics
      depended critically on the properties of (e.g. errors in) the input data and the
      available long range information, these approaches hindered designing an error
      free WGSA pipeline. RESULTS: We dispense with the idea of limiting the solutions
      to just the approximated ones, and instead favor an approach that could
      potentially lead to an exhaustive (exponential-time) search of all possible
      layouts. Its computational complexity thus must be tamed through a constrained
      search (Branch-and-Bound) and quick identification and pruning of implausible
      overlays. For his purpose, such a method necessarily relies on a set of score
      functions (oracles) that can combine different structural properties (e.g.
      transitivity, coverage, physical maps, etc.). We give a detailed description of
      this novel assembly framework, referred to as Scoring-and-Unfolding Trimmed Tree
      Assembler (SUTTA), and present experimental results on several bacterial genomes
      using next-generation sequencing technology data. We also report experimental
      evidence that the assembly quality strongly depends on the choice of the minimum
      overlap parameter k. AVAILABILITY AND IMPLEMENTATION: SUTTA's binaries are freely
      available to non-profit institutions for research and educational purposes at
      http://www.bioinformatics.nyu.edu.

PMID- 21088024
TI  - PETcofold: predicting conserved interactions and structures of two multiple
      alignments of RNA sequences.
AB  - MOTIVATION: Predicting RNA-RNA interactions is essential for determining the
      function of putative non-coding RNAs. Existing methods for the prediction of
      interactions are all based on single sequences. Since comparative methods have
      already been useful in RNA structure determination, we assume that conserved RNA
      RNA interactions also imply conserved function. Of these, we further assume that
      a non-negligible amount of the existing RNA-RNA interactions have also acquired
      compensating base changes throughout evolution. We implement a method, PETcofold,
      that can take covariance information in intra-molecular and inter-molecular base
      pairs into account to predict interactions and secondary structures of two
      multiple alignments of RNA sequences. RESULTS: PETcofold's ability to predict RNA
      RNA interactions was evaluated on a carefully curated dataset of 32 bacterial
      small RNAs and their targets, which was manually extracted from the literature.
      For evaluation of both RNA-RNA interaction and structure prediction, we were able
      to extract only a few high-quality examples: one vertebrate small nucleolar RNA
      and four bacterial small RNAs. For these we show that the prediction can be
      improved by our comparative approach. Furthermore, PETcofold was evaluated on
      controlled data with phylogenetically simulated sequences enriched for covariance
      patterns at the interaction sites. We observed increased performance with
      increased amounts of covariance. AVAILABILITY: The program PETcofold is available
      as source code and can be downloaded from http://rth.dk/resources/petcofold.

PMID- 21088027
TI  - GPU-BLAST: using graphics processors to accelerate protein sequence alignment.
AB  - MOTIVATION: The Basic Local Alignment Search Tool (BLAST) is one of the most
      widely used bioinformatics tools. The widespread impact of BLAST is reflected in
      over 53,000 citations that this software has received in the past two decades,
      and the use of the word 'blast' as a verb referring to biological sequence
      comparison. Any improvement in the execution speed of BLAST would be of great
      importance in the practice of bioinformatics, and facilitate coping with ever
      increasing sizes of biomolecular databases. RESULTS: Using a general-purpose
      graphics processing unit (GPU), we have developed GPU-BLAST, an accelerated
      version of the popular NCBI-BLAST. The implementation is based on the source code
      of NCBI-BLAST, thus maintaining the same input and output interface while
      producing identical results. In comparison to the sequential NCBI-BLAST, the
      speedups achieved by GPU-BLAST range mostly between 3 and 4. AVAILABILITY: The
      source code of GPU-BLAST is freely available at
      http://archimedes.cheme.cmu.edu/biosoftware.html.

PMID- 21088028
TI  - GSearcher: agile attribute querying for biological networks.
AB  - SUMMARY: GSearcher provides a highly interactive user experience in navigating
      attribute data associated with large and complex biological networks. The user
      may either perform a quick search using keywords, phrases or regular expressions,
      or build a complex query with a group of filters for efficient and flexible
      exploration of large datasets. AVAILABILITY:
      http://brainarray.mbni.med.umich.edu/gsearcher/.

PMID- 21088029
TI  - Efficient change point detection for genomic sequences of continuous
      measurements.
AB  - MOTIVATION: Knowing the exact locations of multiple change points in genomic
      sequences serves several biological needs, for instance when data represent aCGH
      profiles and it is of interest to identify possibly damaged genes involved in
      cancer and other diseases. Only a few of the currently available methods deal
      explicitly with estimation of the number and location of change points, and
      moreover these methods may be somewhat vulnerable to deviations of model
      assumptions usually employed. RESULTS: We present a computationally efficient
      method to obtain estimates of the number and location of the change points. The
      method is based on a simple transformation of data and it provides results quite
      robust to model misspecifications. The efficiency of the method guarantees
      moderate computational times regardless of the series length and the number of
      change points. AVAILABILITY: The methods described in this article are
      implemented in the new R package cumSeg available from the Comprehensive R
      Archive Network at http://CRAN.R-project.org/package=cumSeg.

PMID- 21088030
TI  - Anatomy of a hash-based long read sequence mapping algorithm for next generation
      DNA sequencing.
AB  - MOTIVATION: Recently, a number of programs have been proposed for mapping short
      reads to a reference genome. Many of them are heavily optimized for short-read
      mapping and hence are very efficient for shorter queries, but that makes them
      inefficient or not applicable for reads longer than 200 bp. However, many
      sequencers are already generating longer reads and more are expected to follow.
      For long read sequence mapping, there are limited options; BLAT, SSAHA2, FANGS
      and BWA-SW are among the popular ones. However, resequencing and personalized
      medicine need much faster software to map these long sequencing reads to a
      reference genome to identify SNPs or rare transcripts. RESULTS: We present AGILE
      (AliGnIng Long rEads), a hash table based high-throughput sequence mapping
      algorithm for longer 454 reads that uses diagonal multiple seed-match criteria,
      customized q-gram filtering and a dynamic incremental search approach among other
      heuristics to optimize every step of the mapping process. In our experiments, we
      observe that AGILE is more accurate than BLAT, and comparable to BWA-SW and
      SSAHA2. For practical error rates (< 5%) and read lengths (200-1000 bp), AGILE is
      significantly faster than BLAT, SSAHA2 and BWA-SW. Even for the other cases,
      AGILE is comparable to BWA-SW and several times faster than BLAT and SSAHA2.
      AVAILABILITY: http://www.ece.northwestern.edu/~smi539/agile.html.

PMID- 21088031
TI  - Comparison of dipyrone/propofol versus fentanyl/propofol anaesthesia during
      surgery in rabbits.
AB  - In this study, the investigation of the intraoperative effects of dipyrone
      (metamizol) on heart rate (HR), mean arterial pressure (MAP) and analgesic
      efficacy in rabbits is described for the first time. This was carried out to
      evaluate the cardiovascular stability achieved using dipyrone compared with
      fentanyl. In this prospective study, 17 female New Zealand White rabbits were
      randomly allocated to either one of two groups: dipyrone/propofol (DP) or
      fentanyl/propofol (FP). Anaesthesia was induced in both groups using propofol to
      effect (4.0-8.0 mg/kg intravenously) until the swallowing reflex was lost for
      intubation. After induction, anaesthesia was maintained with continuous infusion
      of propofol 1.5-1.7 mg/kg/min intravenously. Analgesics were then injected in
      defined boluses of either dipyrone 65 mg/kg or fentanyl 0.0053 mg/kg. After
      surgical tolerance, defined as loss of the ear pinch reflex and loss of the
      anterior and posterior pedal withdrawal reflex, was achieved, two surgical
      procedures were performed. The surgical procedures (implantation of either a
      pacemaker or an electrocardiogram transmitter), both require a comparable level
      of analgesic depth. During and after surgery, clinical variables, such as MAP,
      HR, peripheral arterial oxygen saturation (SpO2) and end-tidal CO2 (P(E')CO2)
      were recorded simultaneously every 2 min. Eight time points were chosen for
      comparison: baseline, surgical tolerance (ST), values at 10, 20 and 30 min after
      reaching ST, values at the end of propofol infusion (EI) and data at 10 and 20
      min after EI. Both FP and DP combinations provided effective anaesthesia and
      analgesia in rabbits. In both groups a significant decrease of HR and MAP was
      measured. The results of this study indicate that the non-opioid drug dipyrone
      produces similar analgesic and even better cardiovascular effects by trend in
      rabbits. Therefore we conclude that dipyrone in combination with propofol can be
      used as an alternative to FP for intraoperative analgesia.

PMID- 21088032
TI  - The Gold Standard Publication Checklist (GSPC) for improved design, reporting and
      scientific quality of animal studies GSPC versus ARRIVE guidelines.

PMID- 21088033
TI  - A study of psychological symptoms, family function, marital and life
      satisfactions of polygamous and monogamous women: the Palestinian case.
AB  - BACKGROUND: Polygamy is defined as a marriage in which a spouse of either gender
      has more than one mate at the same time. Polygamy is considered a valid form of
      marriage in many countries and communities around the globe. AIM: The purpose of
      this study is to examine the psychological symptoms, family function, marital
      satisfaction, life satisfaction and the degree of agreement with the practice of
      polygamy among 'senior wives' - the first wife in the polygamous marriage - and
      women in monogamous marriages in the West Bank, Palestine. METHOD: A convenience
      sample of 309 women, 187 from polygamous and 122 from monogamous families,
      participated in this study. All women from polygamous families were senior wives.
      The following instruments were deployed: the McMaster Family Assessment Device
      (FAD), the ENRICH marital satisfaction questionnaire, the SCL-90 mental health
      symptoms checklist, the Rosenberg self-esteem (SE) scale, the Diener et al.
      (1985), a life satisfaction scale, and a basic socio-demographic scale, including
      the degree of agreement of the practice of polygamy. RESULTS: The findings
      revealed significant differences between senior wives in polygamous marriages and
      wives in monogamous marriages with regard to family functioning, marital
      satisfaction, self-esteem and life satisfaction. Likewise, many of the mental
      health symptoms were different. Particularly noteworthy were somatization,
      depression, hostility psychotism and the General Severity Index (a global index
      of distress). More women in polygamous marriages agreed with the practice of
      polygamy than their monogamous counterparts. CONCLUSION: Practitioners and policy
      makers need to be aware of the consequences of polygamy on first wives and on
      society as whole.

PMID- 21088034
TI  - Burden of care among relatives of patients with schizophrenia in midwestern
      Nigeria.
AB  - BACKGROUND: Schizophrenia is a devastating mental disorder which places immense
      burden on family members. There are few studies that have explored the enormity
      of burden experienced by caregivers in sub-Saharan Africa. METHOD: Two hundred
      caregivers who were relatives of 200 consecutive outpatients with a diagnosis of
      schizophrenia and undergoing treatment at the Federal Psychiatric Hospital,
      Uselu, Benin, between August and November 2008, were studied. The degree of
      burden experienced by the caregivers was assessed using the Burden Questionnaire
      (BQ). The patients' symptomatology was assessed using the Positive and Negative
      Syndrome Scale (PANSS). RESULTS: Mean financial burden score was significantly
      greater than the mean scores for burden of disruption of family routine and
      interaction, social stigma and subjective distress. Caregivers of unemployed
      patients had significantly higher mean burden scores compared to those of
      employed patients. Level of burden showed significant associations with
      caregivers' educational level, age of patient, employment status of patients and
      global rating of difficulty in coping with caregiving. CONCLUSION: Caregivers of
      patients with schizophrenia experience immense burden. Public health education as
      well as targeted interventions in the area of employment, financial and other
      support for persons with mental disorders would help to ameliorate this burden.

PMID- 21088035
TI  - Examining differences in the stigma of depression and schizophrenia.
AB  - BACKGROUND: Although there is evidence of greater stigmatization of schizophrenia
      in comparison to depression, there has been little investigation of the reasons
      for this difference. AIMS: To examine the role of beliefs about depression and
      schizophrenia in mediating the difference in preferred social distance towards
      individuals with these two disorders. METHODS: In Study I, 200 undergraduates
      completed questionnaires concerning beliefs about depression or schizophrenia and
      willingness to interact with an individual who has one of the two disorders. In
      Study II, 103 members of a community service club completed similar measures.
      RESULTS: For both samples, beliefs about likely appropriateness of social
      behaviour showed evidence of mediating differences in preferred level of social
      distance. In addition, differences in perceived danger may have been a mediator
      for the undergraduate sample and perceived prognosis for the service club
      respondents. CONCLUSIONS: Beliefs about social appropriateness, danger and
      prognosis, which have implications for likely costs and benefits of interaction,
      are more likely to mediate differences in social distance towards the disorders
      than beliefs concerning causation or continuity with normal experience.

PMID- 21088036
TI  - Powhiri process in mental health research.
AB  - Within the health research context, indigenous people globally have a commitment
      to provide their own solutions. Maori, the indigenous people of Aotearoa (New
      Zealand) value the traditional Powhiri process of engagement and participation in
      mental health research. The practices and protocols within the Powhiri process
      (use in the Doctorate of Philosophy (2010) and Auckland University) are premised
      on the notion of respect and positive relationships between the tangata whenua
      (hosts or research participants) and manuwhiri (guests or researchers). This
      paper briefly describes the Powhiri process, which may be a model applicable to
      research with other indigenous cultures.

PMID- 21088037
TI  - Employment status influences suicide mortality in Europe.
AB  - BACKGROUND: The present study attempted to assess the relationship between
      suicide mortality and employment status in Europe. METHODS: Suicide trends were
      obtained from the World Health Organization, employment rates from the Conference
      Board Total Economy Database, and questions about citizens' attitudes towards
      employment from the European Social Survey. Correlations were analysed.
      Differences between mean scores for attitudes in Western and Eastern Europe were
      calculated. RESULTS: Employment and suicide trends are negatively correlated in
      most countries. Suicide mortality is associated with unemployment risk and
      expectations of inadequate financial resources during unemployment, and
      negatively correlated with an assured high standard of living for the unemployed.
      Suicide mortality and the degree of conviction that the government should ensure
      jobs for all are weakly correlated. Attitudes towards employment and unemployment
      in Eastern and Western Europe diverge. CONCLUSIONS: Changes in employment rates
      influence suicide mortality in many European countries. Factors that increase
      suicide mortality include lack of confidence in employment status and unemployed
      people's expectations of insufficient income and low living standards. Suicidal
      behaviour is more strongly related to attitudes linked with employment status
      among males than females. In Eastern Europe the status of being unemployed is
      feared more, and people rely more on the government.

PMID- 21088038
TI  - The impact of LABA+ICS fixed combinations on morbidity and economic burden of
      COPD in Italy: a six-year observational study.
AB  - BACKGROUND: In Italy, chronic obstructive pulmonary disease (COPD) has
      progressively received increasing attention in the last decade, and its impact
      has been investigated extensively in both clinical and pharmacoeconomic terms.
      METHODS: In 2004, the national health authorities stated the appropriateness of
      long-acting beta(2) agonists (LABA) and inhaled corticosteroids (ICS) fixed
      combinations for treating COPD, even though this pharmaceutical option was
      limited to the severe and very severe stages of the disease (forced expiratory
      volume in one second [FEV(1)] <50% predicted). The effectiveness in primary care
      of this official recommendation has been investigated in 1125 COPD patients
      together with the appropriateness of the therapeutic approach to the disease.
      RESULTS: and conclusions: Clinical and economic outcomes were monitored over the
      3 years before (2001-2003) and the 3 years following this recommendation (2004
      2006), and statistically compared (t-test). In general, the overall impact of
      COPD changed progressively after the pronunciation of the public health
      authorities. In particular, since the point when LABA/ICS fixed combinations were
      officially recommended, both morbidity of COPD and the corresponding consumption
      of healthcare resources have progressively lowered. Moreover, the appropriateness
      of the pharmaceutical approach increased in the same period, thus emphasizing the
      importance of the optimization of therapeutic strategies in reducing the long
      term impact of the disease.

PMID- 21088039
TI  - Correlation of rat cortical Fas-associated death domain (FADD) protein
      phosphorylation with the severity of spontaneous morphine abstinence syndrome:
      role of alpha(2)-adrenoceptors and extracellular signal-regulated kinases.
AB  - Fas-associated death domain (FADD) phosphorylation was recently implicated in
      opiate-induced neuroplasticity. To further explore the role of FADD in the
      mechanisms of morphine-induced physical dependence, the regulation of cortical p
      FADD (and their interactions with alpha(2)-adrenoceptors and other signalling
      pathways) was assessed during spontaneous opiate withdrawal (SW) in morphine
      dependent rats (10-100 mg/kg for 6 days). The main results indicated that
      oligomeric p-FADD in the cerebral cortex mirrored the time course of morphine SW
      (12-96 h), which resulted in a striking correlation between p-FADD and the
      intensity (behavioural scores) of morphine abstinence (Spearman correlation
      coefficient: 0.59, n = 39, p < 0.0001). The inactivation of brain alpha(2)
      adrenoceptors (EEDQ at SW 12 h) further enhanced morphine abstinence intensity
      and cortical p-FADD content at SW 24 h. The disruption of ERK1/2 signalling (SL
      327 at SW 4 h and SW 8 h) did not alter morphine abstinence at SW 12 h, but it
      attenuated the behavioural syndrome at SW 24 h. This inhibition of ERK1/2,
      however, did not prevent the up-regulation of oligomeric p-FADD at SW 12 h and 24
      h. These data indicate that cortical oligomeric p-FADD, mainly through an
      interaction with inhibitory alpha(2)-adrenoceptors, plays a functional role in
      the behavioural expression of morphine abstinence in rats.

PMID- 21088040
TI  - Increased expression of the 5-HT6 receptor by viral mediated gene transfer into
      posterior but not anterior dorsomedial striatum interferes with acquisition of a
      discrete action-outcome task.
AB  - Serotonin plays a role in reinforcement learning; however, it is not known which
      serotonin receptors mediate these effects. Serotonin 6 (5-HT(6)) receptors are
      abundant in the striatum, a brain area that is involved in reinforcement
      learning. We previously found that 5-HT(6) receptors in the dorsomedial striatum
      (DMS) affect reinforcement learning or consolidation over several days. We use
      viral-mediated gene transfer to discern the role that 5-HT(6) receptors play in
      mediating post-synaptic responses in anterior versus posterior DMS. Male Long
      Evans rats were used to study learning acquisition during a single session of 100
      trials on a fixed interval of 20 seconds. In a discrete action-outcome learning
      task, rats had 10 seconds to press a lever to induce lever retraction and sucrose
      pellet delivery. In another group of rats, the task had a lever that was
      continuously extended but only active every 20 seconds, allowing for repetitive,
      mostly non-reinforced, lever pressing. Results demonstrate that increased
      expression of 5-HT(6) receptors in the posterior DMS interferes with earning
      sucrose pellets in only the former task. We take this to indicate that 5-HT(6)
      receptor signaling in the posterior DMS interferes with acquisition of discrete
      action-outcome responding.

PMID- 21088041
TI  - Clinical practice with anti-dementia drugs: a revised (second) consensus
      statement from the British Association for Psychopharmacology.
AB  - The British Association for Psychopharmacology (BAP) coordinated a meeting of
      experts to review and revise its first (2006) Guidelines for clinical practice
      with anti-dementia drugs. As before, levels of evidence were rated using accepted
      standards which were then translated into grades of recommendation A to D, with A
      having the strongest evidence base (from randomized controlled trials) and D the
      weakest (case studies or expert opinion). Current clinical diagnostic criteria
      for dementia have sufficient accuracy to be applied in clinical practice (B) and
      brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors
      (donepezil, rivastigmine, and galantamine) are effective for mild to moderate
      Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease
      (A). Until further evidence is available other drugs, including statins, anti
      inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for
      the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase
      inhibitors nor memantine are effective in those with mild cognitive impairment
      (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and
      may cause agitation (A), though selective serotonin reuptake inhibitors may help
      behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be
      used for the treatment of people with Lewy body dementias (Parkinson's disease
      dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric
      symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive
      improvements in DLB (A). There is no clear evidence that any intervention can
      prevent or delay the onset of dementia. Although the consensus statement focuses
      on medication, psychological interventions can be effective in addition to
      pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel
      pharmacological approaches involving strategies to reduce amyloid and/or tau
      deposition are in progress. Although results of pivotal studies are awaited,
      results to date have been equivocal and no disease-modifying agents are either
      licensed or can be currently recommended for clinical use.

PMID- 21088042
TI  - PD168077, a D(4) receptor agonist, reverses object recognition deficits in rats:
      potential role for D(4) receptor mechanisms in improving cognitive dysfunction in
      schizophrenia.
AB  - This study investigated the effects of the dopamine D(4) receptor agonist,
      PD168077, on recognition memory using a novel object recognition task, which
      detects disruption and improvement of recognition memory in rats by measuring
      their ability to discriminate between familiar and novel objects. When
      acquisition and test were 6 h apart (experiment 1), control rats failed to
      discriminate between familiar and novel objects at test. Rats given low doses of
      PD168077 (0.3; 1.0 mg/kg) also failed to discriminate between the objects, while
      rats given higher doses (3.0; 10.0 mg/kg) explored the novel object more than the
      familiar object, indicating retained memory of the familiar object. Thus, at
      higher doses, PD168077 improved recognition memory in rats. Experiment 2 tested
      whether PD168077 would attenuate deficits in novel object recognition induced by
      sub-chronic phencyclidine. Testing was 1 min after acquisition, such that vehicle
      pre-treated rats differentiated between the novel and familiar objects: however,
      sub-chronic phencyclidine-treated rats failed to discriminate between the two,
      indicating disruption of recognition memory. PD168077 (10 mg/kg) restored the
      ability of phencyclidine-treated rats to differentiate between the novel and
      familiar objects, indicating improved recognition memory. The results suggest
      that D(4) receptor activation can improve cognitive dysfunction in an animal
      model relevant to schizophrenia.

PMID- 21088043
TI  - Effect of antipsychotics on spontaneous hyperactivity and hypersensitivity to MK
      801-induced hyperactivity in rats prenatally exposed to methylazoxymethanol.
AB  - Exposure to methylazoxymethanol (MAM) at embryonic day 17 (E17) in the rat has
      been proposed to be a promising model for schizophrenia that mimics behavioural
      abnormalities and deficits in prefrontal cortex (PFC) networks. In this study, we
      investigated for the first time the effects of antipsychotics on abnormal
      behaviours observed in prenatally MAM-exposed rats. We first examined spontaneous
      and MK-801-induced locomotor activity in an open field in adult E17 MAM- or
      saline-exposed rats. Then, the effect of single injections of haloperidol,
      clozapine and risperidone was investigated in MAM- or sham-exposed rats on
      spontaneous and MK-801 (0.05 mg/kg)-induced hyperactivity. Risperidone more
      selectively counteracted the spontaneous hyperactivity in MAM than in sham rats,
      while haloperidol and clozapine induced similar effects on spontaneous locomotion
      in both groups. The main result of this study is that all the tested
      antipsychotics were more effective in attenuating the MK-801-induced
      hyperlocomotion in MAM than in sham rats. These findings further support the
      validity of E17 MAM exposure as a model for schizophrenia and add to its
      heuristic value in screening therapies for schizophrenia.

PMID- 21088044
TI  - The efficacy of natalizumab in patients with multiple sclerosis according to
      level of disability: results of an observational study.
AB  - BACKGROUND: Little is known about how the level of disability at the start of
      treatment with natalizumab affects its efficacy. OBJECTIVES: The aim of this
      study was to investigate the effect of natalizumab on relapses in patients with
      different levels of baseline disability associated with MS. METHODS: This single
      centre observational study collected demographic data for patients followed
      prospectively and who were scheduled to start natalizumab therapy due to the
      presence of disease activity. The annualized relapse rate (ARR) and Kurtzke
      Expanded Disability Status Scale scores were analysed for the previous year, on
      starting treatment (baseline) and 1 year after starting therapy. RESULTS: Seventy
      seven patients (mean age: 39.0 years, mean disease duration: 12.4 years) were
      included. The difference between ARR before and after starting treatment was 0.92
      for baseline Expanded Disability Status Scale <= 3.5 (p < 0.0005), 0.70 for
      Expanded Disability Status Scale 4.0-6.0 (p < 0.007) and 0.57 for Expanded
      Disability Status Scale >= 6 (p = 0.386). Expanded Disability Status Scale did
      not vary during the study. One patient discontinued treatment due to an adverse
      event and nine patients discontinued due to positive anti-natalizumab antibodies.
      CONCLUSIONS: The findings support the efficacy of natalizumab in reducing ARR in
      the year after starting treatment in patients with baseline Expanded Disability
      Status Scale <= 6.

PMID- 21088045
TI  - Comparison of temperature rise interpretations in the rabbit pyrogen test among
      Chinese, Japanese, European, and United States pharmacopeias and 2-2-2
      theoretical models proposed by S. Hoffmann.
AB  - Although the rabbit pyrogen test is one of the crucial methods included in each
      pharmacopeia to evaluate the safety of parenteral medicine, the experimental
      procedures and pyrogen result judgment algorithms (PRJAs) are still greatly
      different from one another. In the first stage of testing, original data of 879
      batches from a total of 2637 rabbits in our laboratory were judged by PRJAs in
      the Chinese Pharmacopoeia 2005 III, the Japanese Pharmacopoeia XIV, the Japanese
      Pharmacopoeia XV, the European Pharmacopeia 6.0, the United States Pharmacopoeia
      32 NF27 and two theoretical models proposed by S. Hoffmann, respectively. The
      results were analyzed to evaluate the effects of various PRJAs. It was shown
      that: (i) the significant differences in the results judged by various
      pharmacopeias and Hoffmann's theoretical models were mainly due to the PRJAs and
      the great differences in PRJAs should be harmonized throughout the world based on
      balance of reducing animal use and guaranteeing the safety of medicines; (ii) it
      is better to use PRJAs that depend on the threshold of the sum of temperature
      rise of all tested rabbits than those that depend on the number of rabbits that
      are over the threshold of temperature rise of individual rabbit according to
      clinical proof and the experimental data; and (iii) the PRJA of the Japanese
      Pharmacopoeia XV has obvious advantages when the total suspicious rate of samples
      was less than 10%. Additionally, a new PRJA designed for reducing the additional
      experiment stages and animal consumption is promoted for evaluation.

PMID- 21088046
TI  - Immune alterations after selective rapid eye movement or total sleep deprivation
      in healthy male volunteers.
AB  - We investigated the impact of two nights of total sleep deprivation (SD) or four
      nights of rapid eye movement (REM) SD on immunological parameters in healthy men.
      Thirty-two volunteers were randomly assigned to three protocols (control, total
      SD or REM SD). Both SD protocols were followed by three nights of sleep recovery.
      The control and REM SD groups had regular nights of sleep monitored by
      polysomnography. Circulating white blood cells (WBCs), T- (CD4/CD8) and B
      lymphocytes, Ig classes, complement and cytokine levels were assessed daily. Two
      nights of total SD increased the numbers of leukocytes and neutrophils compared
      with baseline levels, and these levels returned to baseline after 24 h of sleep
      recovery. The CD4(+) T-cells increased during the total SD period (one and two
      nights) and IgA levels decreased during the entire period of REM SD. These levels
      did not return to baseline after three nights of sleep recovery. Levels of
      monocytes, eosinophils, basophils and cytokines (IL-1beta, IL-2, IL-4, IL-6, IL
      10, TNF-alpha and IFN-gamma) remained unchanged by both protocols of SD. Our
      findings suggest that both protocols affected the human immune profile, although
      in different parameters, and that CD4(+) T-cells and IgA levels were not re
      established after sleep recovery.

PMID- 21088047
TI  - Both inflammatory and classical lipolytic pathways are involved in
      lipopolysaccharide-induced lipolysis in human adipocytes.
AB  - High fat diet-induced endotoxaemia triggers low-grade inflammation and lipid
      release from adipose tissue. This study aims to unravel the cellular mechanisms
      leading to the lipopolysaccharide (LPS) effects in human adipocytes. Subcutaneous
      pre-adipocytes surgically isolated from patients were differentiated into mature
      adipocytes in vitro. Lipolysis was assessed by measurement of glycerol release
      and mRNA expression of pro-inflammatory cytokines were evaluated by real-time
      PCR. Treatment with LPS for 24 h induced a dose-dependent increase in interleukin
      (IL)-6 and IL-8 mRNA expression. At 1 ug/ml LPS, IL-6 and IL-8 were induced to
      19.5 +/- 1.8-fold and 662.7 +/- 91.5-fold (P < 0.01 vs basal), respectively. From
      100 ng/ml to 1 ug/ml, LPS-induced lipolysis increased to a plateau of 3.1-fold
      above basal level (P < 0.001 vs basal). Co-treatment with inhibitors of
      inhibitory kappa B kinase kinase beta (IKKbeta) or NF-kappaB inhibited LPS
      induced glycerol release. Co-treatment with the protein kinase A (PKA) inhibitor
      H-89, the lipase inhibitor orlistat or the hormone-sensitive lipase (HSL)
      inhibitor CAY10499 abolished the lipolytic effects of LPS. Co-treatment with the
      MAPK inhibitor, U0126 also reduced LPS-induced glycerol release. Inhibition of
      lipolysis by orlistat or CAY10499 reduced LPS-induced IL-6 and IL-8 mRNA
      expression. Induction of lipolysis by the synthetic catecholamine isoproterenol
      or the phosphodiesterase type III inhibitor milrinone did not alter basal IL-6
      and IL-8 mRNA expression after 24 treatments whereas these compounds enhanced LPS
      induced IL-6 and IL-8 mRNA expression. Both the inflammatory IKKbeta/NF-kappaB
      pathway and the lipolytic PKA/HSL pathways mediate LPS-induced lipolysis. In
      turn, LPS-induced lipolysis reinforces the expression of pro-inflammatory
      cytokines and, thereby, triggers its own lipolytic activity.

PMID- 21088048
TI  - Ron receptor deficient alveolar myeloid cells exacerbate LPS-induced acute lung
      injury in the murine lung.
AB  - Previous studies have shown that the Ron receptor tyrosine kinase is an important
      regulator of the acute lung inflammatory response induced by intranasal
      administration of bacterial LPS. Compared to wild-type mice, complete loss of the
      Ron receptor in all cell types in vivo was associated with increased lung damage
      as determined by histological analyses and several markers of lung injury
      including increases in pro-inflammatory cytokines such as TNF-alpha. Tumor
      necrosis factor-alpha is a multifunctional cytokine secreted by macrophages,
      which plays a major role in inflammation and is a central mediator of several
      disease states including rheumatoid arthritis and sepsis. Based on increased TNF
      alpha production observed in the Ron-deficient mice, we hypothesized that Ron
      receptor function in the inflammatory cell compartment is essential for the
      regulating lung injury in vivo. To test this hypothesis, we generated myeloid
      lineage-specific Ron-deficient mice. In this study, we report that loss of Ron
      signaling selectively in myeloid cells results in increased lung injury following
      intranasal administration of LPS as measured by increases in TNF-alpha
      production, ensuing neutrophil accumulation and increased lung histopathology.
      These findings corroborate the role of Ron receptor tyrosine kinase as a negative
      regulator of inflammation and further demonstrate the in vivo significance of Ron
      signaling selectively in myeloid cells as a major regulator of this response in
      vivo. These data authenticate Ron as a potential target in innate immunity and
      TNF-alpha-mediated pathologies.

PMID- 21088049
TI  - Association of genetic variants of mannan-binding (MBL) lectin-2 gene, MBL levels
      and function in ulcerative colitis and Crohn's disease.
AB  - Ulcerative colitis and Crohn's disease are the two major forms of inflammatory
      bowel disease (IBD). A series of reports have hypothesized interplay of genetic
      and environmental factors in the pathogenesis of IBD. Polymorphism in the mannan
      binding lectin-2 (MBL-2) gene is known to affect the structural assembly and
      function thereby predisposing subjects to various diseases. The present study was
      designed to evaluate effect of MBL-2 gene polymorphism on MBL levels and function
      in IBD patients. Genomic DNA was isolated from blood samples collected from 157
      ulcerative colitis, 42 Crohn's disease and 204 control subjects. Genotyping for
      different polymorphic sites at exon1 of MBL-2 gene was performed by refractory
      mutation system-PCR and amplification followed by restriction digestion (PCR
      RFLP). Serum MBL concentration and C4 deposition levels were estimated using
      ELISA. Mannan-binding lectin-2 genotypic variants were calculated in IBD and
      healthy controls. The frequency of single nucleotide polymorphisms at codon 54
      was significantly higher in ulcerative colitis patients than controls (P <
      0.0001). Ulcerative colitis patients with 'codon 54'-variation showed low serum
      MBL concentrations coupled with altered MBL function compared to controls. In
      conclusion, single nucleotide polymorphism in the MBL-2 gene is an important risk
      factor significantly affecting MBL levels and function in the development of
      ulcerative colitis among Indians.

PMID- 21088050
TI  - CXC chemokine ligand 4 (CXCL4) down-regulates CC chemokine receptor expression on
      human monocytes.
AB  - During acute inflammation, monocytes are essential in abolishing invading micro
      organisms and encouraging wound healing. Recruitment by CC chemokines is an
      important step in targeting monocytes to the inflamed tissue. However, cell
      surface expression of the corresponding chemokine receptors is subject to
      regulation by various endogenous stimuli which so far have not been
      comprehensively identified. We report that the platelet-derived CXC chemokine
      ligand 4 (CXCL4), a known activator of human monocytes, induces down-regulation
      of CC chemokine receptors (CCR) 1, -2, and -5, resulting in drastic impairment of
      monocyte chemotactic migration towards cognate CC chemokine ligands (CCL) for
      these receptors. Interestingly, CXCL4-mediated down-regulation of CCR1, CCR2 and
      CCR5 was strongly dependent on the chemokine's ability to stimulate
      autocrine/paracrine release of TNF-alpha. In turn, TNF-alpha induced the
      secretion CCL3 and CCL4, two chemokines selective for CCR1 and CCR5, while the
      secretion of CCR2-ligand CCL2 was TNF-alpha-independent. Culture supernatants of
      CXCL4-stimulated monocytes as well as chemokine-enriched preparations thereof
      reproduced CXCL4-induced CCR down-regulation. In conclusion, CXCL4 may act as a
      selective regulator of monocyte migration by stimulating the release of
      autocrine, receptor-desensitizing chemokine ligands. Our results stress a co
      ordinating role for CXCL4 in the cross-talk between platelets and monocytes
      during early inflammation.

PMID- 21088051
TI  - Nucleotide-binding oligomerization domain-containing protein 2 regulates
      suppressor of cytokine signaling 3 expression in Burkholderia pseudomallei
      infected mouse macrophage cell line RAW 264.7.
AB  - Burkholderia pseudomallei, a causative agent of melioidosis, is a facultative
      intracellular Gram-negative bacterium that can survive and multiply inside the
      macrophages. Toll-like receptors are one class of pattern recognition receptors
      (PRRs) that have been documented to play significant role in B. pseudomallei
      infection. In the present study, we investigated a potential role of nucleotide
      binding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2),
      cytoplasmic pattern recognition receptors, in B. pseudomallei-infected mouse
      macrophage cell line RAW 264.7. Both live and heat-killed B. pseudomallei were
      able to up-regulate NOD1 and NOD2 expression in a time-dependent manner. Marked
      reduction of a negative regulator, suppressor of cytokine signaling 3 (SOCS3),
      expression was observed only in B. pseudomallei-infected NOD2-depleted
      macrophages and not in NOD1-depleted macrophages. The decrease in SOCS3
      expression also led to an increase in IFN-gamma responsiveness as judged by an
      enhanced STAT-1 phosphorylation on tyrosine 701 in the B. pseudomallei-infected
      macrophages. Together, these results suggested that, in addition to using other
      PRRs to evade macrophage defense, B. pseudomallei may also use NOD2 to regulate a
      negative regulator like SOCS3.

PMID- 21088052
TI  - Neisseria meningitidis lipid A mutant LPSs function as LPS antagonists in humans
      by inhibiting TLR 4-dependent cytokine production.
AB  - Lipopolysaccharide is a major constituent of the outer membrane of Gram-negative
      bacteria and important in the induction of pro-inflammatory responses. Recently,
      novel LPS species derived from Neisseria meningitidis H44/76 by insertional
      inactivation of the lpxL1 and lpxL2 genes have been created with a lipid A
      portion consisting of five (penta-acylated lpxL1) or four (tetra-acylated lpxL2)
      fatty acids connected to the glucosamine backbone instead of six fatty acids in
      the wild-type LPS. We show that these mutant LPS-types are poor inducers of
      cytokines (tumor-necrosis factor-alpha, IL-1beta, IL-10, IL-RA) in human
      mononuclear cells. Both penta- and tetra-acylated meningococcal LPSs were able to
      inhibit cytokine production by wild-type Escherichia coli or meningococcal LPS.
      Binding of FITC-labelled E. coli LPS TLR4 transfected Chinese hamster ovary (CHO)
      cells was inhibited by both mutant LPS-types. Experiments with CHO fibroblasts
      transfected with human CD14 and TLR4 showed that the antagonizing effect was
      dependent on the expression of human TLR4. In contrast to the situation in
      humans, lpxL1 LPS has agonistic activity for cytokine production in peritoneal
      macrophages of DBA mice, and exacerbated arthritis in murine collagen induced
      arthritis model. N. meningitidis lipid A mutant LPSs lpxL1 and lpxL2 function as
      LPS antagonists in humans by inhibiting TLR4-dependent cytokine production but
      have agonistic activity in mice.

PMID- 21088053
TI  - Neuropsychiatric disorders and risk factors in carbon monoxide intoxication.
AB  - Neuropsychiatric sequelae may be observed in the late phases of carbon monoxide
      (CO) intoxication. Establishing a link between CO-related neuropsychiatric
      disorders and associated risk factors may decrease morbidity and mortality by
      means of appropriate treatment and counseling. The aim of the present study was
      to determine the relationship between neuropsychiatric outcomes of CO
      intoxication and demographic and clinical variables. Thirty patients who
      presented with CO intoxication and had no known neuropsychiatric disease, and 30
      healthy controls were included. Physical examinations and laboratory tests were
      performed. Following the 1st therapy, they underwent mental and psychiatric tests
      5 times (the time of discharge, during the 1st week, and during the 1st, 3rd, and
      6th months). They underwent cerebral magnetic resonance imaging (MRI) at the end
      of the 1st month. They were evaluated by cognitive function tests at the 6th
      month. Lesions relevant to CO intoxication were detected in 46.7% of the patients
      via cranial computed tomography and in 13.3% via MRI. Evaluation of psychiatric
      tests revealed a clear decrease in cognitive functions, such as immediate memory,
      learning, reaching the criterion, spontaneous recall, attention, visual memory,
      and logical memory. It was found that the patients had anxiety within the 1st
      month, and the frequency of anxiety reached to the value of the control group by
      the end of the 6th month. In conclusion, we suggested that CO intoxication might
      lead to neuropsychiatric disorders. Our results emphasized that in addition to
      standard treatment, neuropsychiatric evaluation should also be performed in
      patients with CO intoxication.

PMID- 21088054
TI  - Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats.
AB  - The aim of this study was designed to evaluate the possible protective effects of
      thymoquinone (TQ) on the lung injury in rats after chronic toluene exposure. The
      rats were randomly allotted into one of three experimental groups: control,
      toluene-treated and toluene-treated with TQ; each group contain 10 animals.
      Control group received 1 mL serum physiologic and toluene treatment was performed
      by inhalation of 3000 parts per million (ppm) toluene, in an 8-hr/day and 6
      day/week order for 12 weeks. The rats in TQ treated group was given TQ (50 mg/kg
      body weight) once a day orally for 12 weeks starting just after toluene exposure.
      Tissue samples were obtained for histopathological investigation. To date, no
      histopathological changes of lung in rats after chronic toluene exposure by TQ
      treatment have been reported. Our study showed that TQ treatment inhibits the
      inflammatory pulmonary responses reducing significantly peribronchial
      inflammatory cell infiltration, alveolar septal infiltration, alveolar edema,
      alveolar exudate, interstitial fibrosis and necrosis formation in toluene-treated
      rats. Our data indicate a significant reduction in the activity of in situ
      identification of apoptosis using terminal dUTP nick end-labeling (TUNEL),
      inducible nitric oxide synthase (iNOS) and a rise in the expression of surfactant
      protein D in lung tissue of toluene-treated with TQ therapy. We believe that
      further preclinical research into the utility of TQ may indicate its usefulness
      as a potential treatment on lung injury after chronic toluene exposure in rats.

PMID- 21088055
TI  - Effect of ELF electric field on some on biochemistry characters in the rat serum.
AB  - The present study has investigated the potential effects of extremely low
      frequency (ELF) electric field exposure on plasma cholesterol and triglyceride
      levels of adult male rats. Sixty rats have been divided into three independent
      groups randomly, 20 of which arranged as controls (without exposure to 50 Hz
      electric field), 20 of which have been exposed to a 50 Hz electric field for 10
      days and 20 of which have been exposed to a 50-Hz electric field for 30 days.
      Levels of total cholesterol and triglyceride in plasma samples have been
      measured. Total cholesterol concentration of the plasma in group 2 with short
      term exposure and group 3 with long-term exposure to 50 Hz EF (65.33 +/- 15.31
      mg/dL and 59.55 +/- 15.01 mg/dL, respectively) has showed significant decrease
      when compared with control groups (70.44 +/- 19.60 mg/dL). Also, plasma
      triglyceride showed similar changes (control: 84.44 +/- 16.79 mg/dL, 67.33 +/-
      15.63 and 51.53 +/- 14.17 mg/dL in group 1 and 2, respectively). Fifty Hz
      electric field may decrease plasma total cholesterol and triglyceride levels in
      rodents significantly, especially with long-term exposure.

PMID- 21088057
TI  - Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy.
AB  - OBJECTIVE: Ipilimumab is a fully human MAB against cytotoxic T-lymphocyte antigen
      4 (CTLA4). CTLA4 negatively regulates immune cell activation. In patients with
      metastatic melanoma, ipilimumab increases survival time and induces complete
      remission in some patients. However, immune-related adverse events including
      endocrinopathies have been reported. Bevacizumab, an angiogenesis inhibitor, has
      been used in combination with ipilimumab in patients with advanced melanoma.
      PATIENTS AND METHODS: In this study, we report three patients who received
      ipilimumab alone or combined with bevacizumab therapy and developed thyroiditis,
      and the first report of euthyroid Graves' ophthalmopathy. RESULTS: Case 1 is a 51
      year-old female who presented with severe eye pain, proptosis, and periorbital
      edema. Laboratory results revealed normal TSH, elevated thyroid antibodies but
      low titer of anti-TSH receptor antibody. Imaging was consistent with Graves'
      ophthalmopathy. Cases 2 and 3 were referred for hyperthyroidism, and workup
      revealed thyroiditis. These three cases suggest that patients with advanced
      melanoma treated with ipilimumab +/- bevacizumab may be susceptible to a variety
      of thyroid disorders. CONCLUSIONS: Anti-CTLA4 therapy has shown promising results
      in treating advanced malignancy such as melanoma and renal carcinoma. A number of
      endocrinopathies, including thyroid disorders, may develop during ipilimumab
      therapy. The association of bevacizumab with endocrinopathies is not clear,
      although a few reports suggest a link to hypothyroidism. All patients on
      ipilimumab and/or bevacizumab therapy should be monitored for signs or symptoms
      of thyroiditis.

PMID- 21088056
TI  - beta-cell function and metabolic control in latent autoimmune diabetes in adults
      with early insulin versus conventional treatment: a 3-year follow-up.
AB  - OBJECTIVES: The optimal treatment of latent autoimmune diabetes in adults (LADA)
      is not established. We explored whether early insulin treatment, which has shown
      beneficial effects in rodents and in human pilot studies, would result in better
      preservation of beta-cell function or metabolic control, compared with
      conventional treatment. SUBJECTS AND METHODS: Glucagon-stimulated C-peptide and
      HbAlc were evaluated at baseline and after 12, 24 and 36 months in 37 patients
      recently diagnosed with diabetes, aged >= 30 years, non-insulin-requiring and
      GADAb and/or ICA positive. Twenty patients received early insulin and 17 received
      conventional treatment (diet +/- oral hypoglycaemic agents (OHA), metformin, some
      and/or sulfonylurea) and insulin when necessary. RESULTS: Level of metabolic
      control, HbAlc, was preserved in the early insulin treated, while it
      significantly deteriorated in the conventionally treated. There was no
      significant difference between the groups in C-peptide after 12, 24 or 36 months,
      or in the decline of C-peptide. Only baseline C-peptide predicted a C-peptide of
      >= 0.5 nmol/l at 36 months. Gender, body mass index, antibody titres or HbAlc did
      not influence the levels of C-peptide or HbAlc at baseline or end-of-study, or
      the decline in C-peptide. Among the diet +/- OHA-treated, 5/17 (30%) developed
      insulin dependency during the follow-up. No major hypoglycaemic events occurred.
      CONCLUSIONS: Early insulin treatment in LADA leads to better preservation of
      metabolic control and was safe. Superior preservation of C-peptide could not be
      significantly demonstrated. Only baseline level of C-peptide significantly
      influenced C-peptide level after 3 years. Further studies exploring the best
      treatment in LADA are warranted.

PMID- 21088058
TI  - Growth retardation in untreated autosomal dominant familial neurohypophyseal
      diabetes insipidus caused by one recurring and two novel mutations in the
      vasopressin-neurophysin II gene.
AB  - OBJECTIVE: Autosomal dominant familial neurohypophyseal diabetes insipidus
      (adFNDI), a disorder caused by mutations in the vasopressin (AVP)-neurophysin II
      (NPII) gene, manifests gradually during early childhood with progressive polyuria
      and polydipsia. Patients are usually treated with synthetic AVP analog. If
      unlimited access to water is provided, prognosis is usually good even in the
      absence of specific treatment. In this study, we describe three families with
      adFNDI, in which growth failure was a prominent complaint, on the clinical and
      molecular level. DESIGN/METHODS: Histories from affected and unaffected family
      members were taken. Height and weight of index patients were recorded
      longitudinally. Patients underwent water deprivation tests, magnetic resonance
      imaging, and genetic analysis. One mutant was studied by heterologous expression
      in cell culture. RESULTS: A total of ten affected individuals were studied. In
      two of the three pedigrees, a novel mutation in the AVP-NPII gene was found. The
      index children in each pedigree showed growth retardation, which was the reason
      for referral in two. In these cases, water intake was tightly restricted by the
      parents in an attempt to overcome suspected psychogenic polydipsia and to improve
      appetite. Once the children were treated by hormone replacement, they rapidly
      caught up to normal weight and height. CONCLUSIONS: Genetic testing and
      appropriate parent counseling should be enforced in adFNDI families to ensure
      adequate treatment and avoid chronic water deprivation, which causes failure to
      thrive.

PMID- 21088059
TI  - Economic evaluation of the removal of tobacco promotional displays in Ireland.
AB  - AIM: To evaluate the short-term economic impact of legislation removing point of
      sale tobacco promotional displays (ie, tobacco displays and other point of sale
      tobacco advertising) in Ireland, implemented July 2009, on cigarette sales across
      a range of categories of retail outlets. METHODS: Cigarette sales were evaluated
      using scanning (weekly data since January 2006) and audit data (bimonthly since
      November 2007) within different retail categories using data sourced from AC
      Nielsen, Ireland. Visual inspection and time-series regression techniques were
      used where appropriate to assess changes in sales over time and in relation to
      the legislation. RESULTS: No change was observed in sales data in any retail
      category over and above seasonal patterns and an underlying downward trend over
      time. Similarly, where available data enabled statistical analysis, there was no
      significant effect in the short term (up to 12 months after implementation) on
      retail sales of tobacco products, over and above seasonal and long-term trends.
      CONCLUSIONS Recent claims of substantial revenue losses and closures of small
      retailers as a direct result of the removal of point of sale tobacco promotional
      displays in Ireland are not borne out by these data. The removal of point of sale
      displays is aimed at reducing the pernicious effects of tobacco advertising on
      children and is therefore likely to have an impact on sales over a much more
      protracted time period. This should enable retailers to adapt over time, perhaps
      using such regulations as an opportunity to play a role in promoting healthier
      products in the local community.

PMID- 21088060
TI  - Evaluation of the removal of point-of-sale tobacco displays in Ireland.
AB  - AIM: To evaluate the short-term impacts of removing point-of-sale tobacco
      displays in Ireland, implemented in July 2009. METHODS: Retailer compliance was
      assessed using audit surveys in 2007, 2008 and 2009. Using a monthly survey of
      1000 adults carried out since 2002, changes in smoking prevalence were assessed;
      attitudes were measured using extra questions added for a 10-month period before
      and after the law. Youth responses were assessed using a cohort of 180 13-15 year
      olds, interviewed in June and August 2009. RESULTS: Immediately following
      implementation, compliance was 97%. Support for the law increased among adults
      after implementation (58% Apr-Jun vs 66% Jul-Dec, p<0.001). Recall of displays
      decreased significantly for adults (49% to 22%; p<0.001), more so among teenagers
      (81% to 22%; p<0.001). There were no significant short-term changes in prevalence
      among youths or adults. The proportion of youths believing more than a fifth of
      children their age smoked decreased from 62% to 46%, p<0.001). Post-legislation,
      14% of adult smokers thought the law had made it easier to quit smoking and 38%
      of teenagers thought it would make it easier for children not to smoke.
      CONCLUSIONS: Compliance was very high and the law was well supported. Recall of
      displays dropped significantly among adults and teenagers post-legislation and
      there were encouraging signs that the law helped de-normalise smoking.

PMID- 21088061
TI  - Uneasy money: the Instituto Carlos Slim de la Salud, tobacco philanthropy and
      conflict of interest in global health.
AB  - In May 2007, the Instituto Carso de la Salud-now Instituto Carlos Slim de la
      Salud (ICSS)-was endowed with US$500 million to focus on priority health issues
      in Latin America, notably issues of 'globalisation and non-communicable
      diseases'. ICSS was soon criticised, however, on the grounds that its funding was
      derived from tobacco industry profits and that its founder Carlos Slim Helu
      remained an active industry principal. Collaboration with ICSS was said to run
      counter to the WHO Framework Convention on Tobacco Control. The Institute's then
      Executive President Julio Frenk disputed these charges. This research employs an
      archive of tobacco industry documents triangulated with materials from
      commercial, media, regulatory and NGO sources to examine the financial relations
      between Slim and the tobacco industry. The paper analyses Slim's continuing
      service to the industry and role in ICSS. It demonstrates a prima facie conflict
      of interest between ICSS's health mission and its founder's involvement in
      cigarette manufacturing and marketing, reflected on ICSS's website as a
      resounding silence on issues of tobacco and health. It is concluded that the
      reliance of international health agencies upon the commercial sector requires
      more robust institutional policies to effectively regulate conflicts of interest.

PMID- 21088062
TI  - Tobacco money and public health.

PMID- 21088064
TI  - Teaching kids to cope with anger: peer education.
AB  - Anger could be an early warning signal of violent behavior. Early peer education
      health promotion in relation to anger management could help children before
      uncontrolled anger becomes a problem in adolescence and adulthood. Peer education
      has been identified as a viable intervention strategy worldwide with various
      prevention programs for youth. The purpose of this article is to describe an
      anger management program (Teaching Kids to Cope with Anger, TKC-A 4th-8th
      graders) co-led by high school peer educators in an urban school district's
      summer school enhancement program. A program of five modules will be described.
      This paper discusses the peer educator implementation and recommendations for
      future implementation.

PMID- 21088065
TI  - An approach to the arsenic status in cardiovascular tissues of patients with
      coronary heart disease.
AB  - Among non-cancer effects of arsenic, cardiovascular diseases have been well
      documented; however, few are known about the arsenic fate in cardiovascular
      tissues. We studied the analytic bioinorganic arsenic behaviour in cardiovascular
      tissues from an arsenic exposure coronary heart disease patient group from
      Antofagasta-Chile against a small unexposed arsenic coronary heart patient group.
      Total arsenic concentrations were measured in pieces of cardiovascular tissues of
      the arsenic-exposed and unexposed coronary heart patient groups by hydride
      generation atomic absorption spectrometry (HG-AAS); speciation analysis was made
      by high performance liquid chromatography-inductively coupled plasma-mass
      spectrometry (HPLC-ICP-MS). Pieces of auricle (AU), mammary artery (MAM),
      saphenous vein (SAP) and fat residuals (FAT) were considered in this study. The
      arsenic concentrations in AU and MAM tissues were significantly different between
      both groups of patients. Also, it was demonstrated that the AU is an 'As(3+)
      target tissue.' Otherwise, linking of the total concentrations of arsenic with
      conditional variables and variables related to medical geology factors allowed us
      to infer that the latter are more important for the cardiovascular risk of
      arsenic exposure in the Antofagasta region. Knowledge of total arsenic and the
      prevalence of the trivalent ion (As(3+)) in the AU of patients could contribute
      to understanding the effect of arsenic on cardiovascular diseases.

PMID- 21088066
TI  - Study of nosocomial urinary tract infections in a pediatric intensive care unit.
AB  - Nosocomial urinary tract infections (NUTI) are one of the commonest infections in
      a Pediatric Intensive Care Unit (PICU). This prospective study was conducted in
      PICU between January and December 2008 to study the incidence, organisms and risk
      factors for NUTI. A total of 287 consecutive patients with >48 h PICU stay and
      sterile admission urine culture, were enrolled and monitored for NUTI (defined as
      per CDC criteria 1988) till discharge or death. Patients with and without NUTI
      were compared with respect to demographics, PRISM scores, primary diagnosis,
      nutritional status and device utilization to identify risk factors. Outcome was
      defined as length of PICU stay and survival or death. There were 69 episodes of
      UTI in 60 (20.9%) patients; incidence being 18 episodes/1000 patient days.
      Candida (52.1%) and Enterococcus (13%) were commonest followed by Escherichia
      coli (11.6%) and Klebsiella pneumoniae (10.1%). Catheterization and duration of
      catheterization were the risk factors for NUTI (p < 0.001). The median length of
      PICU stay was significantly longer in NUTI group compared to non-NUTI group (19
      vs. 8 days, p = 0.001). Mortality rates in both the groups were similar.

PMID- 21088067
TI  - Better surveillance is needed to halt spread of artemisinin resistant malaria.

PMID- 21088070
TI  - New head of US Medicare defends health reforms in brief Senate hearing.

PMID- 21088071
TI  - US healthcare continues to lag behind other countries despite double the costs.

PMID- 21088072
TI  - Depressive symptoms in children and adolescents with chronic physical illness: an
      updated meta-analysis.
AB  - OBJECTIVE: To integrate results of available studies that compared levels of
      depressive symptoms of children and adolescents with chronic physical illness to
      healthy peers or test norms. METHODS: Random-effects meta-analysis was computed
      with 340 studies and 450 subsamples. RESULTS: Children and adolescents with
      chronic illness have, on average, higher levels of depressive symptoms than their
      healthy peers (d = .19 SD units). Differences are strongest for chronic fatigue
      syndrome (d = .94), fibromyalgia (d = .59), cleft lip and palate (d = .54),
      migraine/tension head ache (d = .51), and epilepsy (d = .39). Larger effect sizes
      were found in studies with higher proportion of girls, with a healthy control
      group, from developing countries, published before 1990, and that used parent
      rating or clinician ratings rather than child ratings. CONCLUSIONS: Pediatricians
      and others working with children with chronic illnesses should screen children
      with chronic physical illness for symptoms of psychological distress and make
      appropriate referrals for mental health services, when needed.

PMID- 21088073
TI  - Coprescription of clopidogrel and proton pump inhibitors.

PMID- 21088075
TI  - Wide inequities in health are hidden in urban settings, says report.

PMID- 21088074
TI  - The relation of price of antiretroviral drugs and foreign assistance with
      coverage of HIV treatment in Africa: retrospective study.
AB  - OBJECTIVE: To determine the association of reductions in price of antiretroviral
      drugs and foreign assistance for HIV with coverage of antiretroviral treatment.
      DESIGN: Retrospective study. SETTING: Africa. PARTICIPANTS: 13 African countries,
      2003-8. MAIN OUTCOME MEASURES: A price index of first line antiretroviral therapy
      with data on foreign assistance for HIV was used to estimate the associations of
      prices and foreign assistance with antiretroviral coverage (percentage of people
      with advanced HIV infection receiving antiretroviral therapy), controlling for
      national public health spending, HIV prevalence, governance, and fixed effects
      for countries and years. RESULTS: Between 2003 and 2008 the annual price of first
      line antiretroviral therapy decreased from $1177 (L733; ?844) to $96 and foreign
      assistance for HIV per capita increased from $0.4 to $13.8. At an annual price of
      $100, a $10 decrease was associated with a 0.16% adjusted increase in coverage
      (95% confidence interval 0.11% to 0.20%; 0.19% unadjusted, 0.14% to 0.24%). Each
      additional $1 per capita in foreign assistance for HIV was associated with a 1.0%
      adjusted increase in coverage (0.7% to 1.2%; 1.4% unadjusted, 1.1% to 1.6%). If
      the annual price of antiretroviral therapy stayed at $100, foreign assistance
      would need to quadruple to $64 per capita to be associated with universal
      coverage. Government effectiveness and national public health expenditures were
      also positively associated with increasing coverage. CONCLUSIONS: Reductions in
      price of antiretroviral drugs were important in broadening coverage of HIV
      treatment in Africa from 2003 to 2008, but their future role may be limited.
      Foreign assistance and national public health expenditures for HIV seem more
      important in expanding future coverage.

PMID- 21088078
TI  - Socio-economic differences in dysglycemia and lifestyle-related risk factors in
      the Finnish middle-aged population.
AB  - BACKGROUND: The aim of this study was to investigate the association of socio
      economic status (SES) with dysglycemia and the lifestyle-related risk factors,
      and to analyze to which extent known risk factors explain socio-economic
      differences in diabetes risk. METHODS: Two population-based cross-sectional
      surveys in Finland including 1696 men and 1946 women aged 45-64 years who
      participated in a health examination in 2004 or 2007. Dysglycemia was determined
      by an oral glucose tolerance test. Total type 2 diabetes (including previously
      known and screen-detected type 2 diabetes), impaired glucose tolerance and
      impaired fasting glucose formed the category of total dysglycemia. Questionnaires
      and clinical examination were completed to assess risk factors for dysglycemia.
      SES was defined by education and household income. RESULTS: In both genders, the
      prevalence of total dysglycemia differed statistically significantly between
      educational groups. Low education was statistically significantly associated with
      higher risk of total type 2 diabetes in women. The household income level was
      inversely associated with total type 2 diabetes in women and with total
      dysglycemia in men. Obesity, unhealthy diet and smoking were all inversely
      related to SES in both men and women. The observed association between education
      and dysglycemia was slightly attenuated after adjustment for obesity and other
      risk factors for diabetes. CONCLUSIONS: Low education was associated with an
      increased risk of dysglycemia more strongly than the low household income. Risk
      factors, especially obesity, explained only partly the observed associations
      between dysglycemia and education.

PMID- 21088079
TI  - Women's perception as a barrier to focused antenatal care in Nigeria: the issue
      of fewer antenatal visits.
AB  - The attitude of pregnant women to a new antenatal care model with four antenatal
      visits (focused antenatal care) is examined using a cross-sectional survey in
      Enugu, Nigeria. Only 20.3% of the parturients desired a change to the new model.
      Parturients who defaulted from antenatal care three or more times, those
      dissatisfied with their current antenatal care, senior civil servants and
      parturients who received secondary school education or less most commonly desired
      a change to the new model (P < 0.05). Default from antenatal care and
      dissatisfaction with current antenatal care were most predictive of the desire
      for change in multiple logistic regression analysis. The most common reasons for
      desiring the change were convenience (65.1%) and cost considerations (24.1%).
      Reasons given for the rejection of the new model were: fear of inadequate
      learning during antenatal care (45.7%), the suspicion that four visits were
      inadequate for familiarization with care providers (12.9%), the need for early
      detection of disease (6.7%) and social satisfaction from antenatal visits (6.7%).
      These concerns are amenable to change by health education and social
      mobilization.

PMID- 21088080
TI  - Ureteric sarcoidosis--a rare entity.
AB  - Primary ureteric involvement in sarcoidosis is very rare; to our knowledge, only
      a few cases have been reported in the literature. We present here a rare case of
      ureteric sarcoidosis presenting with obstructive uropathy.

PMID- 21088081
TI  - Cardiac magnetic resonance imaging illustrating Anderson-Fabry disease
      progression.
AB  - Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from a
      deficiency of the enzyme alpha-galactosidase A (alpha-Gal A) and subsequent
      cellular storage of the enzyme's substrate globotriaosylceramide (Gb3) and
      related glycosphingolipids. We report a case of Anderson-Fabry disease with
      cardiac involvement evaluated with cardiovascular MRI. Disease progression was
      observed despite enzyme replacement therapy.

PMID- 21088082
TI  - Hepatic artery pseudoaneurysms arising from within a hepatocellular carcinoma.
AB  - We report a case of a 70-year-old man with a large hepatocellular carcinoma (HCC)
      containing two pseudoaneurysms measuring up to 2 cm in diameter. The
      pseudoaneurysms and part of the HCC were supplied by branches from the middle
      colic artery, which arises from the superior mesenteric artery. This complex
      arterial vasculature was visualised on CT and confirmed with conventional
      angiography.

PMID- 21088083
TI  - A case of pneumonitis and encephalitis associated with human herpesvirus 6 (HHV
      6) infection after bone marrow transplantation.
AB  - Human herpesvirus 6 (HHV-6)-associated encephalitis or pneumonitis has been
      reported in immunocompetent and immunosuppressed individuals. Several MRI studies
      in patients with HHV-6-associated encephalitis have been presented. However, to
      the best of our knowledge, no studies describing thin-section CT imaging in
      patients with HHV-6-associated pneumonitis have been reported. Here we describe a
      case of HHV-6-associated encephalitis and pneumonitis that developed after bone
      marrow transplantation. Thin-section CT images of the chest revealed ground-glass
      attenuation, consolidation and centrilobular nodules in both lungs.

PMID- 21088084
TI  - Metastatic meningioma: positron emission tomography CT imaging findings.
AB  - The imaging findings of a case of metastasing meningioma are described. The case
      illustrates a number of rare and interesting features. The patient presented with
      haemoptysis 22 years after the initial resection of an intracranial meningioma.
      CT demonstrated heterogeneous masses with avid peripheral enhancement without
      central enhancement. Blood supply to the larger lesion was partially from small
      feeding vessels from the inferior pulmonary vein. These findings correlate with a
      previously published case in which there was avid uptake of fluoro-18
      deoxyglucose peripherally with lesser uptake centrally. The diagnosis of
      metastasing meningioma was confirmed on percutaneous lung tissue biopsy.

PMID- 21088085
TI  - Molecular radiotherapy--the radionuclide raffle?

PMID- 21088087
TI  - Treatment of acute middle cerebral artery occlusion with a Solitaire AB stent:
      preliminary experience.
AB  - We report our initial experience with a Solitaire AB neurovascular remodeling
      stent device in performing cerebral embolectomy in seven patients presenting to
      our institution with acute stroke who were resistant to iv thrombolytic drug
      treatment. The main inclusion criteria were: National Institutes of Health Stroke
      Scale (NIHSS) score >=10; treatment performed within 8 h from the onset of
      symptoms and no large hypodensity on CT; and occlusion of a major cerebral artery
      on the CT angiogram. An admission and a post-interventional NIHSS score were
      calculated for all patients by two different neurologists. Efficacy was assessed
      radiologically by post-treatment thrombolysis in myocardial infarction (TIMI)
      scores and clinically by a 30-day Modified Rankin Scale (MRS) score. The mean
      duration of neurointerventional treatment was 84 min. All interventions were
      successful, with TIMI scores of 2 or 3 achieved in 100% of patients. There was
      one procedural complication in our series owing to a self-detached stent and one
      patient had a small asymptomatic basal ganglia haemorrhage. There was improvement
      of more than 4 points on the NIHSS score in 5 (72%) of the patients following
      treatment, of whom 4 (57%) had a 30-day MRS score of <=2. The use of a Solitaire
      stent in acute stroke was safe, time-efficient and encouraging; however, a larger
      sample size will be required to further evaluate the use of this device, which
      could benefit a significant number of stroke patients.

PMID- 21088086
TI  - Pneumonia in the immunocompetent patient.
AB  - Pneumonia is an acute inflammation of the lower respiratory tract. Lower
      respiratory tract infection is a major cause of mortality worldwide. Pneumonia is
      most common at the extremes of life. Predisposing factors in children include an
      under-developed immune system together with other factors, such as malnutrition
      and over-crowding. In adults, tobacco smoking is the single most important
      preventable risk factor. The commonest infecting organisms in children are
      respiratory viruses and Streptoccocus pneumoniae. In adults, pneumonia can be
      broadly classified, on the basis of chest radiographic appearance, into lobar
      pneumonia, bronchopneumonia and pneumonia producing an interstitial pattern.
      Lobar pneumonia is most commonly associated with community acquired pneumonia,
      bronchopneumonia with hospital acquired infection and an interstitial pattern
      with the so called atypical pneumonias, which can be caused by viruses or
      organisms such as Mycoplasma pneumoniae. Most cases of pneumonia can be managed
      with chest radiographs as the only form of imaging, but CT can detect pneumonia
      not visible on the chest radiograph and may be of value, particularly in the
      hospital setting. Complications of pneumonia include pleural effusion, empyema
      and lung abscess. The chest radiograph may initially indicate an effusion but
      ultrasound is more sensitive, allows characterisation in some cases and can guide
      catheter placement for drainage. CT can also be used to characterise and estimate
      the extent of pleural disease. Most lung abscesses respond to medical therapy,
      with surgery and image guided catheter drainage serving as options for those
      cases who do not respond.

PMID- 21088088
TI  - Radiation dose evaluation in multidetector-row CT imaging for acute stroke with
      an anthropomorphic phantom.
AB  - This study evaluated radiation dose and dose reduction in CT imaging for acute
      stroke. Radiation doses in three types of CT imaging (i.e. non-contrast-enhanced
      CT, CT perfusion (CTP) and CT angiography (CTA)) were measured with an in-phantom
      dosimetry system for 4-, 16- and 64-detector CT scanners in 5 hospitals. To
      examine the relationship between image quality and radiation dose in CTA, image
      contrast-to-noise ratio was evaluated. Doses to the brain, lens, salivary glands
      and local skin obtained with scan protocols in routine use were: 42-71 mGy, 30-88
      mGy, 3.9-7.3 mGy and 40-97 mGy in non-contrast-enhanced CT; 41-75 mGy, 9.9-10
      mGy, 1.5-2.1 mGy and 107-143 mGy in CTP; and 8.2-55 mGy, 26-69 mGy, 2.0-73 mGy
      and 32-72 mGy in CTA. For the combination of these CT examinations, on average a
      patient would receive 236 mGy for the maximum local skin dose and 4.2 mSv for the
      effective dose evaluated by the International Commission on Radiological
      Protection (ICRP) 103. Effective doses in CTP in this study were less than those
      obtained with representative protocols of Western countries. Average effective
      doses in each CT examination were not more than 1.5 mSv. The use of reduced kV
      and a narrow scan range would be effective in dose reduction of CTA and CTP, and
      intermittent scanning would be essential in CTP. Although lens and maximum local
      skin doses were far less than the thresholds for deterministic effects, since
      radiation risks would be increased in repeated CT examinations, efforts should be
      devoted to dose reduction in stroke CT examinations.

PMID- 21088089
TI  - Population exposure to ionising radiation from CT examinations in Aosta Valley
      between 2001 and 2008.
AB  - Recent and continuous advances in CT, such as the development of multislice CT,
      have promoted a rapid increase in its clinical application. Today, CT accounts
      for approximately 10% of the total number of medical radiographic procedures
      worldwide. However, the growing performance of the new CT generations have
      increased not only the diagnostic opportunities, but also the radiation dose to
      the patient. The relative contribution to the collective radiation dose is now
      estimated to be approximately 50%. Several papers have been published concerning
      the intensive use of CT and its contribution to the collective dose. However,
      most of the literature concerns the years 1997-2003 and the dosimetric
      evaluations are generally limited to the main standard protocols (chest, head and
      abdomen), deriving the effective dose by the simple application of the diagnostic
      reference levels. Only specific dosimetric analyses of single and innovative
      procedures have been published recently. Moreover, few data comes from Italian
      radiology departments. This paper aims to bridge these gaps. Firstly, it
      characterises in terms of measured CT dose index (CTDI) two last-generation
      scanners of the Radiological Department of Aosta Hospital. Secondly, it evaluates
      the effective dose from most of the CT examinations performed from 2001 to 2008
      to compare protocols and technologies in line with the suggestions of the 2007
      Recommendations of the International Commission on Radiological Protection,
      Publication 103. Finally, it estimates the collective dose to the population.

PMID- 21088091
TI  - Coverage of axillary lymph nodes with high tangential fields in breast
      radiotherapy.
AB  - The aim of this study is to evaluate the coverage of axillary nodal volumes with
      high tangent fields (HTF) in breast radiotherapy and to determine the utility of
      customised blocking. The treatment plans of 30 consecutive patients with early
      breast cancer were evaluated. The prescription dose was 50 Gy to the whole
      breast. Axillary level I-II lymph node volumes were delineated and the cranial
      border of the tangential fields was set just below the humeral head to create
      HTF. Dose-volume histograms (DVH) were used to calculate the doses received by
      axillary nodal volumes. In a second planning set, HTF were modified with
      multileaf collimators (MLC-HTF) to obtain an adequate dose coverage of axillary
      nodes. The mean doses of the axillary nodes, the ipsilateral lung and heart were
      compared between the two plans (HTF vs MLC-HTF) using a paired sample t-test. The
      doses received by 95% of the breast volumes were not significantly different for
      the two plans. The doses received by 95% of the level I and II axillary volumes
      were 16.79 Gy and 11.59 Gy, respectively, for HTF, increasing to 47.2 Gy and
      45.03 Gy, respectively, for MLC-HTF. Mean lung doses and per cent volume of the
      ipsilateral lung receiving 20 Gy (V20) were also increased from 6.47 Gy and
      10.47%, respectively, for HTF, to 9.56 Gy and 16.77%, respectively, for MLC-HTF.
      Our results suggest that HTF do not adequately cover the level I and II axillary
      lymph node regions. Modification of HTF with MLC is necessary to obtain an
      adequate coverage of axillary levels without compromising healthy tissue in the
      majority of the patients.

PMID- 21088090
TI  - CT evaluations of focal liver reactions following stereotactic body radiotherapy
      for small hepatocellular carcinoma with cirrhosis: relationship between imaging
      appearance and baseline liver function.
AB  - This study aimed to assess the imaging appearances of focal liver reactions
      following stereotactic body radiotherapy (SBRT) for small hepatocellular
      carcinoma (HCC) and to examine relationships between imaging appearance and
      baseline liver function. We retrospectively studied 50 lesions in 47 patients
      treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for
      more than 6 months. After SBRT, all patients underwent regular follow-ups with
      blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2
      43.7 months), all lesions but one were controlled. 3 density patterns describing
      focal normal liver reactions around HCC tumours were identified in pre-contrast,
      arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A),
      low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients
      (Type C). Imaging changes in the normal liver surrounding the treated HCC began
      at a median of 3 months after SBRT, peaked at a median of 6 months and
      disappeared 9 months later. Liver function, as assessed by the Child-Pugh
      classification, was the only factor that differed significantly between reactions
      to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C)
      appearances in CT. Hence, liver tissue with preserved function is more likely to
      be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The
      CT appearances of normal liver seen in reaction to the treatment of an HCC by
      SBRT were therefore related to background liver function and should not be
      misread as recurrence of HCC.

PMID- 21088092
TI  - CT-guided radiofrequency liver tumour ablation: use of a two-step coaxial system
      with a fine guide needle wire unit for high-risk cases.
AB  - Accurate radiofrequency (RF) needle targeting to liver lesions under CT guidance
      is technically difficult and generally requires multiple needle manipulations,
      which carries potential risk. This approach is hardly applicable for precariously
      located lesions or for patients who have difficulty holding their breath. The aim
      of this study was to develop a novel two-step coaxial system to facilitate CT
      guided RF ablation in difficult cases. The study group comprised 11 patients with
      12 hepatic lesions. The coaxial system consisted of two parts: a 21-gauge pencil
      tip guide needle wire (GNW) unit comprising a 150-mm-long needle segment and a
      250-mm-long wire segment; and a 140-mm-long outer cannula with its stylet, which
      accepts a 17-gauge RF electrode needle. The GNW was inserted until the route of
      the GNW was confirmed to be positioned correctly. The cannula with the stylet was
      then advanced along the GNW. Lesions were successfully accessed using the GNW,
      even in patients who could not hold their breath, and manipulation was feasible
      within the limited space of the CT gantry. The light GNW also facilitated step-by
      step CT-guided angular manipulations, unlike heavy RF electrodes, which are
      unstable during hands-free use unless deeply inserted. Therefore, this system
      enabled sequential ablations of large tumours by ensuring three different routes
      in advance by using the GNW. Insertion of the cannula along the GNW was simple.
      In conclusion, the two-step coaxial system enabled CT-guided RF tumour ablation
      to be performed in cases conventionally contraindicated owing to high risk of
      serious complications.

PMID- 21088093
TI  - An atypical cause of trigeminal neuralgia and panhypopituitarism.

PMID- 21088095
TI  - Efficacy and safety of nebivolol in Hispanics with stage I-II hypertension: a
      randomized placebo-controlled trial.
AB  - OBJECTIVE: Hispanics have lower rates of hypertension control compared with black
      and white patients. Nebivolol is a vasodilatory beta1-selective blocker, with
      neutral metabolic effects. This phase IV trial evaluated the efficacy and safety
      of nebivolol in Hispanics with stage I-II hypertension. METHODS: Self-identified
      Hispanics with stage I-II hypertension were randomized to receive a double-blind
      treatment: placebo (n = 136) or nebivolol (n = 141, starting dose 5 mg/day) for 8
      weeks. Nebivolol dosage could be uptitrated at 2-week intervals to 10, 20, or 40
      mg/day, as needed to achieve diastolic blood pressure (DBP) control (JNC7
      criteria). Efficacy outcome measures were the mean changes from baseline to the
      end of week 8 in trough-seated DBP (primary) and systolic blood pressure (SBP)
      (secondary). Safety and tolerability were also assessed. RESULTS: Baseline
      SBP/DBP (mmHg) was similar in both treatment groups (nebivolol: 156/100; placebo:
      157/101). A total of 135 (96%) and 121 (89%) nebivolol- and placebo-treated
      participants completed the double-blind phase, respectively. Compared with the
      placebo, nebivolol treatment was associated with significant mean reductions in
      both trough-seated DBP and SBP (DBP: -11.1 mmHg vs. -7.3 mmHg, p < 0.0001; SBP: 
      14.1 mmHg vs. -9.3 mmHg; p = 0.001). Treatment-emergent adverse event (TEAE)
      rates were 17% (nebivolol) and 22% (placebo); the most frequent TEAEs were
      headache (4% vs. 6%, respectively), upper respiratory tract infection (2% vs.
      2%), and dizziness (1% vs. 3%). CONCLUSIONS: In Hispanics with stage I-II
      hypertension, 8-week nebivolol monotherapy resulted in significant reductions in
      blood pressure. The safety and tolerability profile of nebivolol was similar to
      that of placebo.

PMID- 21088097
TI  - The content of talk about health conditions and medications during appointments
      involving interpreters.
AB  - INTRODUCTION: Interpreters often join immigrants and physicians to permit
      communication. OBJECTIVE: To describe the content of talk about health problems
      and medications during clinical encounters involving interpreters [professionals
      (PI) or family members (FI)]. METHODS: We analysed one regularly scheduled
      encounter for each of 16 adult patients with his family physician and their usual
      interpreter (10 with a PI and 6 with a FI). A different PI, not involved in the
      consultations, translated the non-English or French parts. We coded all
      utterances about each medical problem and each medication using six health
      problem and 16 medication topics from MEDICODE, a validated coding scheme.
      RESULTS: Physicians and patients addressed an average of 3.6 problems and 3
      medications per encounter. No psychosocial problems were discussed in encounters
      involving FIs. On average, three topics were discussed per problem. In order of
      frequency, they were follow-up, explanations of the condition, non-drug
      management, consequences, self-management and emotions about the problem.
      Encounters involving PIs were more likely than encounters with FIs to include
      discussions of emotions about the problem (42% versus 4%, P = 0.001) and
      indications for follow-up (88% versus 28%, P < 0.001). An average of 6.5 topics
      was discussed per medication. Commonest topics discussed were medication class,
      how the drug was being used, achieved effect and expected effect. CONCLUSIONS:
      One can address multiple problems and share vital information even in the
      presence of a language barrier. When FIs are interpreting, physicians would do
      well to make a particular effort to bring the patient's psychological and
      emotional issues into the interaction.

PMID- 21088098
TI  - Transhumanism, metaphysics, and the posthuman god.
AB  - After describing Heidegger's critique of metaphysics as ontotheology, I unpack
      the metaphysical assumptions of several transhumanist philosophers. I claim that
      they deploy an ontology of power and that they also deploy a kind of theology, as
      Heidegger meant it. I also describe the way in which this metaphysics begets its
      own politics and ethics. In order to transcend the human condition, they must
      transgress the human.

PMID- 21088099
TI  - Editorial: Child and community mental health in cultural perspective.

PMID- 21088100
TI  - The McDonaldization of childhood: children's mental health in neo-liberal market
      cultures.
AB  - As the failings of neo-liberalism have recently been revealed through the
      collapse of much of the banking and financial services sector, it seems an
      opportune time to think about the impact this economic, political, and social
      value system has had on the well-being of children. After analyzing how our
      beliefs and practices around children and families are shaped by a variety of
      economic, political, and cultural pressures, I discuss how policies that promote
      a particular form of aggressive capitalism lead to a narcissistic value system
      that permeates social institutions, including those that deal with children. Not
      only does this impact children's emotional well-being, but it also shapes the way
      we conceptualize children and their problems. These dynamics facilitate the rapid
      growth of child psychiatric diagnoses and the tendency to deal with aberrant
      behavior or emotions in children through technical--particularly pharmaceutical-
      interventions, a phenomenon I refer to as the 'McDonaldization' of children's
      mental health. The present article seeks to challenge many of the unhelpful
      cultural assumptions regarding childhood embedded within the narrow biomedical
      frame that neo-liberalism has encouraged.

PMID- 21088101
TI  - Multicultural evidence-based assessment of child and adolescent psychopathology.
AB  - This article presents multicultural ways to advance knowledge of children's
      problems, to fashion conceptual and practical mental health tools, and to use
      these tools to help children. Diagnostically based scales and statistically
      derived syndromes are scored from parallel forms completed by population samples
      of parents, caregivers, teachers, and youths in many societies. The scores are
      incorporated into multicultural norms for evaluating individual children, as
      rated by different respondents in relation to relevant norms, such as norms for
      host societies where immigrant children reside and norms for their families' home
      societies. Syndrome structures have been supported in 44 societies. Certain age,
      gender, and SES effects are consistent across many societies. As reported in over
      7000 publications from 85 societies and cultural groups, evidence-based
      assessment provides a common data language for clinicians, trainees, and
      researchers around the world.

PMID- 21088102
TI  - Social ecology of child soldiers: child, family, and community determinants of
      mental health, psychosocial well-being, and reintegration in Nepal.
AB  - This study employed a social ecology framework to evaluate psychosocial well
      being in a cross-sectional sample of 142 former child soldiers in Nepal. Outcome
      measures included the Depression Self Rating Scale (DSRS), Child Posttraumatic
      Stress Disorder Symptom Scale (CPSS), and locally developed measures of
      functional impairment and reintegration. Hierarchical linear modeling was used to
      examine the contribution of factors at multiple levels. At the child level,
      traumatic exposures, especially torture, predicted poor outcomes, while education
      improved outcomes. At the family level, conflict-related death of a relative,
      physical abuse in the household, and loss of wealth during the conflict predicted
      poor outcomes. At the community level, living in high caste Hindu communities
      predicted lack of reintegration supports. Ultimately, social ecology is well
      suited to identify intervention foci across ecological levels based on community
      differences in vulnerability and protective factors.

PMID- 21088104
TI  - Mental health service utilization of Somali adolescents: religion, community, and
      school as gateways to healing.
AB  - This mixed-method study examines the utility of the Gateway Provider Model (GPM)
      in understanding service utilization and pathways to help for Somali refugee
      adolescents. Somali adolescents living in the Northeastern United States, and
      their caregivers, were interviewed. Results revealed low rates of use of mental
      health services. However other sources of help, such as religious and school
      personnel, were accessed more frequently. The GPM provides a helpful model for
      understanding refugee youth access to services, and an elaborated model is
      presented showing how existing pathways to help could be built upon to improve
      refugee youth access to services.

PMID- 21088103
TI  - Development of a measure of "acculturation" for ethnic Fijians: methodologic and
      conceptual considerations for application to eating disorders research.
AB  - Acculturation has been examined as a risk factor for eating disorders, but
      interpretation of findings has been limited by inconsistent operationalization of
      this construct across studies. The study aim was to develop and evaluate a
      population-specific measure of acculturation for ethnic Fijian adolescent
      schoolgirls, to use in future analyses related to eating disorders. Our findings
      suggest that acculturation is a multidimensional construct characterized by
      distinct, though related, dimensions of orientation to ethnic Fijian and/or
      western/global culture with respect to a range of behaviors and attitudes. In
      contrast to theoretical models positing uni-dimensional, orthogonal, or oblique
      relations between cultural identities in individuals undergoing acculturation,
      our study findings support a heterogeneous pattern among correlations of
      dimensions across contrasting cultural identities. We suggest multidimensional
      measures of acculturation are optimal--and socio-demographic proxies inadequate-
      for characterization of this complex process for health research.

PMID- 21088105
TI  - The role of acculturation in suicidal ideation among second-generation immigrant
      adolescents in France.
AB  - This study explored the contributions of sociocultural and psychopathological
      factors to suicidal ideation among adolescents. A sample of 292 French high
      school students with an immigrant background completed a questionnaire assessing
      suicidal ideation, borderline personality traits, depressive symptoms, parental
      attachment, life events, acculturation orientations, ethnic identity, cannabis
      and alcohol consumption, socioeconomic status and academic failure. Although
      stressful life events, depressive symptoms, and individualism were risk factors,
      and attachment to parents a protective factor for both boys and girls, some
      gender differences emerged. Borderline traits (risk factor), assimilation and
      marginalization (both protective factors) were significant predictors only among
      girls.

PMID- 21088106
TI  - Associations between genetic variation in RUNX1, RUNX2, RUNX3, MAPK1 and eIF4E
      and riskof colon and rectal cancer: additional support for a TGF-beta-signaling
      pathway.
AB  - The Runt-related transcription factors (RUNX), mitogen-activated protein kinase
      (MAPK) 1 and eukaryotic translation initiation factor 4E (eIF4E) are potentially
      involved in tumorigenesis. We evaluated genetic variation in RUNX1 (40 tagSNPs),
      RUNX2 (19 tagSNPs), RUNX3 (9 tagSNPs), MAPK1 (6 tagSNPs), eIF4E (3 tagSNPs),
      eIF4EBP2 (2 tagSNP) and eIF4EBP3 (2 tagSNPs) to determine associations with
      colorectal cancer (CRC). We used data from population-based studies (colon cancer
      n = 1555 cases, 1956 controls; rectal cancer n = 754 cases, 959 controls with
      complete genotype data). Four statistically significant tagSNPs were identified
      with colon cancer and three tagSNPs were identified with rectal cancer. Whereas
      the independent risk estimates for each of the tagSNPs ranged from 1.21 to 1.52,
      the combined risk was greater than additive for any of the three combined high
      risk genotypes {combined risk range 1.98 [95% confidence interval (CI) 1.45,
      2.70] for eIF4E, RUNX1 and RUNX3 to 3.32 [95% CI 1.34, 8.23] for eIF43, RUNX2 and
      RUNX3}. For rectal cancer, the strongest association was detected for the
      combined genotype of RUNX1 and RUNX3 (odds ratio 1.87 95% CI 1.22, 2.87).
      Associations with specific molecular tumor phenotypes showed consistent and
      strong associations for CIMP+/MSI+ tumors where the risk estimates were
      consistently >10-fold and lower confidence bounds were over 3.00 for high-risk
      genotypes defined by RUNX1, RUNX2 and RUNX3. For CIMP+/KRAS2-mutated colon
      tumors, the combined risk for high-risk genotypes of RUNX2, eIF4E and RUNX1 was
      7.47 (95% CI 1.58, 35.3). Although the associations need confirmation, the
      findings and their internal consistency underline the importance of genetic
      variation in these genes for the etiology of CRC.

PMID- 21088107
TI  - Anabaena sp. strain PCC 7120 conR contains a LytR-CpsA-Psr domain, is
      developmentally regulated, and is essential for diazotrophic growth and
      heterocyst morphogenesis.
AB  - The conR (all0187) gene of the filamentous cyanobacterium Anabaena (Nostoc) sp.
      strain PCC 7120 is predicted to be part of a family of proteins that contain the
      LytR-CpsA-Psr domain associated with septum formation and cell wall maintenance.
      The conR gene was originally misannotated as a transcription regulator. Northern
      RNA blot analysis showed that conR expression was upregulated 8 h after nitrogen
      step-down. Fluorescence microscopy of a P(conR)-gfp reporter strain revealed
      increased GFP fluorescence in proheterocysts and heterocysts beginning 9 h after
      nitrogen step-down. Insertional inactivation of conR caused a septum-formation
      defect of vegetative cells grown in nitrate-containing medium. In nitrate-free
      medium, mutant filaments formed abnormally long heterocysts and were defective
      for diazotrophic growth. Septum formation between heterocysts and adjacent
      vegetative cells was abnormal, often with one or both poles of the heterocysts
      appearing partially open. In a conR mutant, expression of nifH was delayed after
      nitrogen step-down and nitrogenase activity was approximately 70 % of wild-type
      activity, indicating that heterocysts of the conR mutant strain are partially
      functional. We hypothesize that the diazotrophic growth defect is caused by an
      inability of the heterocysts to transport fixed nitrogen to the neighbouring
      vegetative cells.

PMID- 21088109
TI  - Non-nearest-neighbor dependence of the stability for RNA group II single
      nucleotide bulge loops.
AB  - Thirty-one RNA duplexes containing single-nucleotide bulge loops were optically
      melted in 1 M NaCl, and the thermodynamic parameters DeltaH degrees , DeltaS
      degrees , DeltaG degrees (37), and T(M) for each sequence were determined. The
      bulge loops were of the group II variety, where the bulged nucleotide is
      identical to one of its nearest neighbors, leading to ambiguity as to the exact
      position of the bulge. The data were used to develop a model to predict the free
      energy of an RNA duplex containing a single-nucleotide bulge. The destabilization
      of the duplex by the bulge was primarily related to the stability of the stems
      adjacent to the bulge. Specifically, there was a direct correlation between the
      destabilization of the duplex and the stability of the less stable duplex stem.
      Since there is an ambiguity of the bulge position for group II bulges, several
      different stem combinations are possible. The destabilization of group II bulge
      loops is similar to the destabilization of group I bulge loops, if the second
      least stable stem is used to predict the influence of the group II bulge. In-line
      structure probing of the group II bulge loop embedded in a hairpin indicates that
      the bulged nucleotide is the one positioned farther from the hairpin loop.

PMID- 21088108
TI  - Contributions of chaperone/usher systems to cell binding, biofilm formation and
      Yersinia pestis virulence.
AB  - Yersinia pestis genome sequencing projects have revealed six intact
      uncharacterized chaperone/usher systems with the potential to play roles in
      plague pathogenesis. We cloned each locus and expressed them in the Deltafim
      Escherichia coli strain AAEC185 to test the assembled Y. pestis surface
      structures for various activities. Expression of each chaperone/usher locus gave
      rise to specific novel fibrillar structures on the surface of E. coli. One locus,
      y0561-0563, was able to mediate attachment to human epithelial cells (HEp-2) and
      human macrophages (THP-1) but not mouse macrophages (RAW264.7), while several
      loci were able to facilitate E. coli biofilm formation. When each chaperone/usher
      locus was deleted in Y. pestis, only deletion of the previously described pH 6
      antigen (Psa) chaperone/usher system resulted in decreased adhesion and biofilm
      formation. Quantitative RT-PCR (qRT-PCR) revealed low expression levels for each
      novel chaperone/usher system in vitro as well as in mouse tissues following
      intravenous infection. However, a Y. pestis mutant in the chaperone/usher locus
      y1858-1862 was attenuated for virulence in mice via the intravenous route of
      infection, suggesting that expression of this locus is, at some stage, sufficient
      to affect the outcome of a plague infection. qRT-PCR experiments also indicated
      that expression of the chaperone/usher-dependent capsule locus, caf1, was
      influenced by oxygen availability and that the well-described chaperone/usher
      dependent pilus, Psa, was strongly induced in minimal medium even at 28  degrees
      C rather than 37  degrees C, a temperature previously believed to be required for
      Psa expression. These data indicate several potential roles for the novel
      chaperone/usher systems of Y. pestis in pathogenesis and infection-related
      functions such as cell adhesion and biofilm formation.

PMID- 21088110
TI  - Enhanced excitation-coupled Ca(2+) entry induces nuclear translocation of NFAT
      and contributes to IL-6 release from myotubes from patients with central core
      disease.
AB  - Prolonged depolarization of skeletal muscle cells induces entry of extracellular
      calcium into muscle cells, an event referred to as excitation-coupled calcium
      entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction
      between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine
      receptor on the sarcoplasmic reticulum membrane. In this study, we directly
      measured excitation-coupled calcium entry by total internal reflection
      fluorescence microscopy in human skeletal muscle myotubes harbouring mutations in
      the RYR1 gene linked to malignant hyperthermia (MH) and central core disease
      (CCD). We found that excitation-coupled calcium entry is strongly enhanced in
      cells from patients with CCD compared with individuals with MH and controls.
      Furthermore, excitation-coupled calcium entry induces generation of reactive
      nitrogen species and enhances nuclear localization of NFATc1, which in turn may
      be responsible for the increased IL-6 released by myotubes from patients with
      CCD.

PMID- 21088111
TI  - Absence of progeria-like disease phenotypes in knock-in mice expressing a non
      farnesylated version of progerin.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutant prelamin A,
      progerin, that terminates with a farnesylcysteine. HGPS knock-in mice
      (Lmna(HG/+)) develop severe progeria-like disease phenotypes. These phenotypes
      can be ameliorated with a protein farnesyltransferase inhibitor (FTI), suggesting
      that progerin's farnesyl lipid is important for disease pathogenesis and raising
      the possibility that FTIs could be useful for treating humans with HGPS.
      Subsequent studies showed that mice expressing non-farnesylated progerin
      (Lmna(nHG/+) mice, in which progerin's carboxyl-terminal -CSIM motif was changed
      to -SSIM) also develop severe progeria, raising doubts about whether any
      treatment targeting protein prenylation would be particularly effective. We
      suspected that those doubts might be premature and hypothesized that the
      persistent disease in Lmna(nHG/+) mice could be an unanticipated consequence of
      the cysteine-to-serine substitution that was used to eliminate farnesylation. To
      test this hypothesis, we generated a second knock-in allele yielding non
      farnesylated progerin (Lmna(csmHG)) in which the carboxyl-terminal -CSIM motif
      was changed to -CSM. We then compared disease phenotypes in mice harboring the
      Lmna(nHG) or Lmna(csmHG) allele. As expected, Lmna(nHG/+) and Lmna(nHG/nHG) mice
      developed severe progeria-like disease phenotypes, including osteolytic lesions
      and rib fractures, osteoporosis, slow growth and reduced survival. In contrast,
      Lmna(csmHG/+) and Lmna(csmHG/csmHG) mice exhibited no bone disease and displayed
      entirely normal body weights and survival. The frequencies of misshapen cell
      nuclei were lower in Lmna(csmHG/+) and Lmna(csmHG/csmHG) fibroblasts. These
      studies show that the ability of non-farnesylated progerin to elicit disease
      depends on the carboxyl-terminal mutation used to eliminate protein prenylation.

PMID- 21088112
TI  - Bidirectional transcription stimulates expansion and contraction of expanded
      (CTG)*(CAG) repeats.
AB  - More than 12 neurogenetic disorders are caused by unstable expansions of
      (CTG)*(CAG) repeats. The expanded repeats are unstable in germline and somatic
      cells, with potential consequences for disease severity. Previous studies have
      shown that contractions of (CAG)(95) are more frequent when the repeat tract is
      transcribed. Here we determined whether transcription can promote repeat
      expansion, using (CTG)*(CAG) repeat tracts in the size range that is typical for
      myotonic dystrophy type 1. We derived normal human fibroblasts having single-copy
      genomic integrations of 800 CTG repeats. The repeat tract showed modest
      instability when it was not transcribed, yielding an estimated mutation rate of
      0.28% per generation. Instability was enhanced several-fold by transcription in
      the forward or reverse transcription, and 30-fold by bidirectional transcription,
      yielding many expansions and contractions of more than 200 repeats. These results
      suggest that convergent bidirectional transcription, which has been reported at
      several disease loci, could contribute to somatic instability of highly expanded
      (CTG)*(CAG) repeats.

PMID- 21088113
TI  - HuD interacts with survival motor neuron protein and can rescue spinal muscular
      atrophy-like neuronal defects.
AB  - Spinal muscular atrophy is an autosomal-recessive neuromuscular disease caused by
      disruption of the survival of motor neuron (SMN) gene, which promotes cytoplasmic
      assembly of the splicing core machinery. It remains unclear how a deficiency in
      SMN results in a disorder leading to selective degeneration of lower motor
      neurons. We report here that SMN interacts with RNA-binding protein HuD in
      neurites of motorneuron-derived MN-1 cells. This interaction is mediated through
      the Tudor domain of SMN and, importantly, naturally occurring Tudor mutations
      found in patients with severe spinal muscular atrophy (SMA) completely abrogate
      the interaction, underscoring its relevance to the disease process. We also
      characterized a regulatory pathway involving coactivator-associated arginine
      methyltransferase 1 (CARM1) and HuD. Specifically, we show that CARM1 expression
      is rapidly downregulated, at the protein level, following induction of
      differentiation through retinoid and neurotrophic signaling. Using purified
      proteins, we demonstrate that methylation of HuD by CARM1 reduces its interaction
      with the p21(cip1/waf1) mRNA, showing that CARM1 can directly influence RNA
      binding activity. We further demonstrate that this CARM1-dependent regulatory
      switch mainly controls the activity of HuD in promoting cell-cycle exit, whereas
      the interaction between HuD and SMN is required for proper recruitment of HuD and
      its mRNA targets in neuronal RNA granules. Finally, we were able to rescue SMA
      like defects in a hypomorphic Smn knockdown MN-1 cell line through overexpression
      of HuD. Together, these findings extend our understanding of specific role(s) of
      SMN in motor neurons and provide crucial insights into potential new avenues for
      SMA therapeutic strategies.

PMID- 21088114
TI  - Comparison of the effect of low-dose ciclesonide and fixed-dose fluticasone
      propionate and salmeterol combination on long-term asthma control.
AB  - BACKGROUND: Patients with mild persistent asthma constitute about 70% of the
      asthma population; thus, it is important to know which first-line treatment is
      best for the management of mild asthma. We compared benefits of first-line
      treatment with ciclesonide and a combination of fluticasone and salmeterol in
      patients with mild asthma. METHODS: Patients aged 12 to 75 years with mild
      persistent asthma were enrolled in a randomized, double-blind, placebo-controlled
      study. After run-in, patients were randomized to ciclesonide 160 MUg once daily
      (CIC160), fluticasone propionate/salmeterol 100/50 MUg bid (FP200/S100), or
      placebo for 52 weeks. The primary variable was time to first severe asthma
      exacerbation; the coprimary variable was the percentage of poorly controlled
      asthma days. Patients recorded asthma symptoms and salbutamol use in electronic
      diaries and completed a standardized version of the Asthma Quality of Life
      Questionnaire. RESULTS: Compared with placebo, the time to first severe asthma
      exacerbation was prolonged, and lung function was improved with FP200/S100
      treatment (P = .0002) but not with CIC160. Both CIC160 and FP200/S100 provided
      significantly fewer poorly controlled asthma days than placebo (P <= .0016 for
      both active treatments). Moreover, both active treatments provided significantly
      more asthma symptom-free days (P <= .0001), rescue medication-free days (P =
      .0005, one-sided), and days with asthma control (P <= .0033). Overall Asthma
      Quality of Life Questionnaire scores were significantly higher in both active
      treatment groups than placebo (P <= .0017). CONCLUSIONS: In mild asthma,
      FP200/S100 prolonged time to first severe asthma exacerbation, and CIC160 and
      FP200/S100 were clinically equieffective for most measures of asthma control.
      TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00163358; URL:
      www.clinicaltrials.gov.

PMID- 21088115
TI  - Urokinase receptor mediates mobilization, migration, and differentiation of
      mesenchymal stem cells.
AB  - AIMS: Multipotent mesenchymal stem cells (MSCs) have regenerative properties and
      are recognized as putative players in the pathogenesis of cardiovascular
      diseases. The underlying molecular mechanisms remain, however, sparsely explored.
      Our study was designed to elucidate a probable role for the multifunctional
      urokinase (uPA)/urokinase receptor (uPAR) system in MSC regulation. Though uPAR
      has been implicated in a broad spectrum of pathophysiological processes, nothing
      is known about uPAR in MSCs. METHODS AND RESULTS: uPAR was required to mobilize
      MSCs from the bone marrow (BM) of mice stimulated with granulocyte colony
      stimulating factor (G-CSF) in vivo. An insignificant amount of MSCs was mobilized
      in uPAR(-/-) C57BL/6J mice, whereas in wild-type animals G-CSF induced an eight
      fold increase of mobilized MSCs. uPAR(-/-) mice revealed up-regulated expression
      of G-CSF and stromal cell-derived factor 1 (CXCR4) receptors in BM. uPAR down
      regulation leads to inhibition of human MSC migration, as shown in different
      migration assays. uPAR down- or up-regulation resulted in inhibition or
      stimulation of MSC differentiation into vascular smooth muscle cells (VSMCs)
      correspondingly, as monitored by changes in cell morphology and expression of
      specific marker proteins. Injection of fluorescently labelled MSCs in non-obese
      diabetic/severe combined immunodeficiency (NOD/SCID) mice after femoral artery
      wire injury demonstrated impaired engraftment of uPAR-deficient MSCs at the place
      of injury. CONCLUSIONS: These data suggest a multifaceted function of uPAR in MSC
      biology contributing to vascular repair. uPAR might guide and control the
      trafficking of MSCs to the vascular wall in response to injury or ischaemia and
      their differentiation towards functional VSMCs at the site of arterial injury.

PMID- 21088117
TI  - Supervised exercises compared with radial extracorporeal shock-wave therapy for
      subacromial shoulder pain: 1-year results of a single-blind randomized controlled
      trial.
AB  - BACKGROUND: Evidence from a recent randomized controlled trial indicated that
      supervised exercises (SE) were more effective than radial extracorporeal shock
      wave therapy (rESWT) for the treatment of subacromial shoulder pain in the short
      to medium term. Little knowledge exists about the long-term results of rESWT for
      subacromial pain. OBJECTIVE: The aim of this study was to evaluate the results of
      rESWT and SE provided to patients with subacromial shoulder pain after 1 year.
      DESIGN: This was a single-blind randomized controlled trial. SETTING: The study
      was conducted in the outpatient clinic of the Physical Medicine and
      Rehabilitation Department at Oslo University Hospital, Ullevaal, Norway.
      PATIENTS: One hundred four patients with subacromial shoulder pain lasting at
      least 3 months participated. Patients were randomly assigned to either an rESWT
      group (n=52) or an SE group (n=52). INTERVENTION: The rESWT intervention
      consisted of one session weekly for 4 to 6 weeks. The SE intervention consisted
      of two 45-minute sessions per week for up to 12 weeks. MEASUREMENTS: The primary
      outcome measure was the Shoulder Pain and Disability Index. Secondary outcome
      measures were questions regarding pain and function and work status. RESULTS:
      After 1 year, an intention-to-treat analysis showed no significant differences
      between the 2 groups for the primary outcome measure (-7.6 points, 95% confidence
      interval=-16.6 to 0.5) and pain, function, and medication use. Twenty-nine
      participants (60%) in the SE group versus 24 participants (52%) in the rESWT
      group were categorized as clinically improved. Thirty-eight participants in the
      SE group were at work compared with 30 participants in the rESWT group (odds
      ratio=1.1, 95% confidence interval=1.0 to 1.2). Fewer patients in the SE group
      had received additional treatments between 18 weeks and 1 year. LIMITATIONS: The
      lack of a placebo control group, the lack of a cost-benefit analysis, and the
      small sample size were limitations of the study. CONCLUSION: No significant
      difference was found between the SE and rESWT groups at the 1-year follow-up.
      More participants in the SE group had returned to work.

PMID- 21088116
TI  - A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and
      impairs insulin signalling.
AB  - AIMS: Obesity and hyperlipidaemia are associated with insulin resistance (IR);
      however, the mechanisms responsible remain incompletely understood. Pro
      atherogenic hyperlipidaemic states are characterized by inflammation, oxidant
      stress, and pathophysiologic oxidized lipids, including ligands for the scavenger
      receptor CD36. Here we tested the hypothesis that the absence of CD36 protects
      mice from IR associated with diet-induced obesity and hyperlipidaemia. METHODS
      AND RESULTS: Adipose tissue from CD36(-/-) mice demonstrated a less inflammatory
      phenotype and improved insulin signalling in vivo and at the level of the
      adipocyte and macrophage. The pathophysiologic ligand oxidized low-density
      lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin
      signalling in both adipocytes and macrophages in a CD36-dependent manner.
      Macrophages isolated from CD36(-/-) mice after high-fat diet feeding elicited
      less JNK activation and inhibition of insulin signalling in adipocytes after co
      culture compared with wild-type macrophages. CONCLUSION: These data suggest that
      a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages
      facilitates chronic inflammation and contributes to IR common in obesity and
      dyslipidaemia.

PMID- 21088118
TI  - Boxing training for patients with Parkinson disease: a case series.
AB  - BACKGROUND AND PURPOSE: A nontraditional form of exercise recently applied for
      patients with Parkinson disease (PD) is boxing training. The primary purpose of
      this case series is to describe the effects of disease severity and duration of
      boxing training (short term and long term) on changes in balance, mobility, and
      quality of life for patients with mild or moderate to severe PD. The feasibility
      and safety of the boxing training program also were assessed. CASE DESCRIPTION:
      Six patients with idiopathic PD attended 24 to 36 boxing training sessions for 12
      weeks, with the option of continuing the training for an additional 24 weeks (a
      seventh patient attended sessions for only 4 weeks). The 90-minute sessions
      included boxing drills and traditional stretching, strengthening, and endurance
      exercises. Outcomes were tested at the baseline and after 12, 24, and 36 weeks of
      boxing sessions (12-, 24-, and 36-week tests). The outcome measures were the
      Functional Reach Test, Berg Balance Scale, Activities-specific Balance Confidence
      Scale, Timed "Up & Go" Test, Six-Minute Walk Test, gait speed, cadence, stride
      length, step width, activities of daily living and motor examination subscales of
      the Unified Parkinson Disease Rating Scale, and Parkinson Disease Quality of Life
      Scale. OUTCOMES: Six patients completed all phases of the case series, showed
      improvements on at least 5 of the 12 outcome measures over the baseline at the 12
      week test, and showed continued improvements at the 24- and 36-week tests.
      Patients with mild PD typically showed improvements earlier than those with
      moderate to severe PD. DISCUSSION: Despite the progressive nature of PD, the
      patients in this case series showed short-term and long-term improvements in
      balance, gait, activities of daily living, and quality of life after the boxing
      training program. A longer duration of training was necessary for patients with
      moderate to severe PD to show maximal training outcomes. The boxing training
      program was feasible and safe for these patients with PD.

PMID- 21088119
TI  - Potential link between ozone and recurrent stroke.

PMID- 21088120
TI  - Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial
      infarction: a systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the accuracy of heart-type fatty acid-binding protein (H
      FABP) as a new and early cardiac biomarker in the early diagnosis of acute
      myocardial infarction (AMI). The introduction of early and safe biomarkers could
      lead to (a) a large reduction in unnecessary hospital referrals of patients
      suspected of, but not, having AMI and (b) an earlier start of treatment in
      patients with AMI. DESIGN: Diagnostic meta-analysis. SETTING: Hospital and pre
      hospital. PATIENTS: Consecutive patients suspected of having AMI. MAIN OUTCOME
      MEASURES: A summary estimate for sensitivity and specificity was calculated using
      the bivariate random-effects approach, and covariate analysis was used to examine
      sources of heterogeneity between studies. RESULTS: A systematic search yielded 16
      studies (3709 patients, prevalence of AMI 13-74%, male gender 49-84%, median age
      64-76 years). The summary estimate was 84% (95% CI 76% to 90%) for sensitivity
      and 84% (95% CI 76% to 89%) for specificity. Covariate analyses revealed that the
      use of troponin in the reference standard for AMI (as opposed to creatine kinase
      or creatine kinase-myocardial band) had a significant impact on sensitivity.
      CONCLUSION: H-FABP does not fulfil the requirements needed for a safe and early
      diagnosis of AMI when used as a stand-alone test. Sound diagnostic studies
      examining the additional role of H-FABP combined with clinical findings and other
      diagnostic tests are needed to further clarify a potential future role for this
      cardiac biomarker.

PMID- 21088121
TI  - Insights into genotype-phenotype correlation in hypertrophic cardiomyopathy.
      Findings from 18 Spanish families with a single mutation in MYBPC3.
AB  - BACKGROUND: Mutations in the cardiac myosin-binding protein C (MYBPC3) gene are
      frequently found as a cause of hypertrophic cardiomyopathy (HCM). However, only a
      few studies have analysed genotype-phenotype correlations in small series of
      patients. The present study sought to determine the clinical characteristics,
      penetrance and prognosis of HCM with an identical mutation in MYBPC3. METHODS:
      154 non-related patients with HCM (aged 55+/-16 years, 100 (64.9%) males) were
      studied. 18 (11.7%) were found to have an identical mutation in the MYBPC3 gene
      (IVS23+1G->A). Pedigree analysis, including both clinical evaluation and
      genotyping, was performed. RESULTS: 152 individuals (mean age 37+/-18 years,
      53.3% males) from 18 families were evaluated. 65 carriers of the IVS23+1G->A
      mutation were identified, 61.5% of whom met HCM diagnostic criteria. Penetrance
      of the disease increased with age, with 50% affected at 46 years of age. Males
      tended to develop the disease earlier than females. 7 (15.6%) had systolic
      dysfunction. Compared with the rest of the HCM cohort, probands with the mutation
      had more hypertrophy and were younger at diagnosis. There was a trend towards a
      reduced survival free from sudden death (SD) (HR 1.71; 95% CI 0.98 to 2.98,
      p=0.059). There were 17 SD cases in 12 families with the mutation. CONCLUSIONS:
      The MYBPC3 IVS23+1G->A mutation is associated with middle-age onset disease and
      poor outcome, with a significant proportion of patients developing systolic
      impairment and a high SD risk profile.

PMID- 21088122
TI  - Echocardiographic assessment of raised pulmonary vascular resistance: application
      to diagnosis and follow-up of pulmonary hypertension.
AB  - OBJECTIVE: To optimise an echocardiographic estimation of pulmonary vascular
      resistance (PVR(e)) for diagnosis and follow-up of pulmonary hypertension (PHT).
      DESIGN: Cross-sectional study. SETTING: Tertiary referral centre. PATIENTS:
      Patients undergoing right heart catheterisation and echocardiography for
      assessment of suspected PHT. METHODS: PVR(e) ([tricuspid regurgitation velocity
      *10/(right ventricular outflow tract velocity-time integral+0.16) and invasive
      PVR(i) ((mean pulmonary artery systolic pressure-wedge pressure)/cardiac output)
      were compared in 72 patients. Other echo data included right ventricular systolic
      pressure (RVSP), estimated right atrial pressure, and E/e' ratio. Difference
      between PVR(e) and PVR(i) at various levels of PVR was sought using Bland-Altman
      analysis. Corrected PVR(c) ((RVSP-E/e')/RVOT(VTI)) (RVOT, RV outflow time; VTI,
      velocity time integral) was developed in the training group and tested in a
      separate validation group of 42 patients with established PHT. RESULTS:
      PVR(e)>2.0 had high sensitivity (93%) and specificity (91%) for recognition of
      PVR(i)>2.0, and PVR(c) provided similar sensitivities and specificities. PVR(e)
      and PVR(i) correlated well (r=0.77, p<0.01), but PVR(e) underestimated marked
      elevation of PVR(i)-a trend avoided by PVR(c). PVR(c) and PVR(e) were tested
      against PVR(i) in a separate validation group (n=42). The mean difference between
      PVR(e) and PVR(i) exceeded that between PVR(c) and PVR(i) (2.8+/-2.7 vs 0.8+/-3.0
      Wood units; p<0.001). A drop in PVR(i) by at least one SD occurred in 10 patients
      over 6 months; this was detected in one patient by PVR(e) and eight patients by
      PVR(c) (p=0.002). CONCLUSION: PVR(e) distinguishes normal from abnormal PVR(i)
      but underestimates high PVR(i). PVR(c) identifies the severity of PHT and may be
      used to assess treatment response.

PMID- 21088123
TI  - Exercise induces biventricular mechanical dyssynchrony in children with repaired
      tetralogy of Fallot.
AB  - OBJECTIVE: The mechanisms underlying adverse electro-mechanical interaction after
      tetralogy of Fallot (TOF) repair remain unclear. This study investigated
      biventricular dyssynchrony in children with TOF and its relationship to exercise,
      QRS duration (QRSd) and ventricular mechanics. METHODS: 29 asymptomatic children
      (5-18 years) with repaired TOF were prospectively evaluated by MRI,
      cardiopulmonary exercise testing and echocardiography at rest and during bicycle
      exertion. Their dyssynchrony results were compared with those of 44 resting and
      27 exercising, age- and sex-matched controls. An intraventricular dyssynchrony
      index was calculated from the SD of regional time intervals in 12 left
      ventricular (LV) 'Ts LV-12SD' and eight right ventricular (RV) 'Ts RV-8SD'
      segments. Ventricular size, volumes, ejection fractions, pulmonary regurgitant
      volumes and peak oxygen consumption and N-terminal BNP levels were quantified in
      the patients. RESULTS: Despite moderate RV dilatation (median indexed RV end
      diastolic volume 145.2 ml/m(2)) and right bundle branch block (median QRSd 130
      ms) compared with controls, children with TOF demonstrated neither RV nor LV
      dyssynchrony at rest (Ts RV-8SD, 37.9+/-10.2 vs 44.3+/-10.3, 95% CI -11.8 to 
      0.99, p=0.02; Ts LV-12SD, 38.6+/-16.8 vs 34.0+/-10.8, 95% CI -1.8 to 11.0,
      p=0.16). Exercise stress induced biventricular dyssynchrony in patients with TOF
      but not in controls (Ts RV-8SD, 59.9+/-34.4 vs 28.2+/-10.4, p<0.0001, 95% CI 17.2
      to 46.3; Ts LV-12SD, 48.0+/-18.6 vs 31.9+/-10.7, 95% CI 7.9 to 24.4, p=0.002).
      This was unrelated to QRSd, ventricular volumes and function, or peak oxygen
      consumption. CONCLUSION: Exercise induces biventricular mechanical dyssynchrony
      in children with TOF.

PMID- 21088124
TI  - Non-invasive evaluation of myocardial fibrosis: implications for the clinician.

PMID- 21088125
TI  - Exercise training in heart failure: practical guidance.

PMID- 21088126
TI  - Two dimensional speckle tracking echocardiography: clinical applications.

PMID- 21088127
TI  - Microbiological and immunological effects of enteral feeding on the upper
      gastrointestinal tract.
AB  - Enteral feeding via a percutaneous endoscopic gastrostomy tube is required for
      nutritional support in patients with dysphagia. Enteral tube feeding bypasses the
      innate defence mechanisms in the upper gastrointestinal tract. This study
      examined the surface-associated microbial populations and immune response in the
      gastric and duodenal mucosae of eight enteral nutrition (EN) patients and ten
      controls. Real-time PCR and fluorescence in situ hybridization were employed to
      assess microbiota composition and mucosal pro-inflammatory cytokine expression.
      The results showed that EN patients had significantly higher levels of bacterial
      DNA in mucosal biopsies from the stomach and duodenum (P<0.05) than the controls,
      and that enterobacteria were the predominant colonizing species on mucosal
      surfaces in these individuals. Expression of the pro-inflammatory cytokines
      interleukin (IL)-1alpha, IL-6 and tumour necrosis factor-alpha was significantly
      higher in gastric and small intestinal mucosae from patients fed normal diets in
      comparison with those receiving EN (P<0.05). These results indicate that EN can
      lead to significant bacterial overgrowth on upper gastrointestinal tract mucosae
      and a significantly diminished pro-inflammatory cytokine response.

PMID- 21088128
TI  - Virulence properties and integron-associated antibiotic resistance of Klebsiella
      mobilis strains isolated from clinical specimens.
AB  - This study examined Klebsiella mobilis isolates cultured from clinical specimens
      for virulence-associated properties and antibiotic resistance. The strains
      produced a number of siderophores, including enterobactin, aerobactin and
      yersiniabactin. All isolates were able to adhere to and invade epithelial cells.
      They had cytotoxic activity, which caused destruction of human laryngeal
      epithelial HEp-2 cells and evoked lysis of murine macrophage J774 cells. Analyses
      of HEp-2 and J774 cellular morphology and DNA fragmentation in the cells showed
      features typical of cells undergoing apoptosis. Some K. mobilis strains harboured
      class 1 integrons carrying the aadA1 gene encoding an aminoglycoside
      adenyltransferase.

PMID- 21088129
TI  - Gas emissions from biodegradable waste in United Kingdom landfills.
AB  - The aim of this research was to predict the effect that the biodegradable
      municipal waste (BMW) diversion targets in the European Union landfill directive
      (99/31/EC) would have on landfill gas emissions. This is important for continued
      mitigation of these emissions. Work was undertaken in three stages using the
      GasSim model (v1.03) developed by the Environment Agency (England and Wales). The
      first stage considered the contribution to gas emissions made by each
      biodegradable component of the waste stream. The second stage considered how gas
      emissions from a landfill accepting biodegradable wastes with reduced
      biodegradable content would be affected. The third stage looked at the
      contribution to gas emissions from real samples of biologically pretreated BMW.
      For the first two stages, data on the waste components were available in the
      model. For the third stage samples were obtained from four different biological
      treatment facilities and the required parameters determined experimentally. The
      results of stage 1 indicated that in the first 15 years of the landfill the
      putrescible fraction makes the most significant contribution, after which
      paper/card becomes the most significant. The second stage found that
      biodegradability must be reduced by at least 60% to achieve a reduction in
      overall methane generation. The third stage found that emissions from samples of
      biologically pretreated BMW would result in a significant reduction in gas
      emissions over untreated waste, particularly in the early stage of the landfill
      lifetime; however, low level emissions would continue to occur for the long term.

PMID- 21088130
TI  - How long and how well: oncologists' attitudes toward the relative value of life
      prolonging v. quality of life-enhancing treatments.
AB  - OBJECTIVE: To determine how oncologists value quality-enhancing v. life
      prolonging outcomes attributable to chemotherapy. METHODS: The authors surveyed a
      random sample of 1379 US medical oncologists (members of the American Society of
      Clinical Oncology), presenting them with 2 scenarios involving a hypothetical new
      chemotherapy drug. Given their responses, the authors derived the implicit cost
      effectiveness ratios each physician attributed to quality-enhancing and life
      prolonging chemotherapies. RESULTS: The authors received responses from 58% of
      the oncologists surveyed. On average, the responses implied that oncologists were
      willing to prescribe treatments that cost $245,972 per quality-adjusted life-year
      (QALY; SD $243,663 per QALY) in life-prolonging situations v. only $119,082 per
      QALY (SD $197,048 per QALY) for treatments that improve quality of life but do
      not prolong survival (P < 0.001). This difference did not depend on age, gender,
      percentage of time in clinical work, or self-reported preparedness to use and
      interpret cost-effectiveness information (P > 0.05 for all specifications).
      Differences across these situations persisted even among those who considered
      themselves to be "well-prepared" to make cost-effectiveness decisions.
      CONCLUSION: Cost-effectiveness thresholds for oncologists vary widely for life
      prolonging chemotherapy compared to treatments that only enhance quality of life.
      This difference suggests that oncologists value length of survival more highly
      than quality of life when making chemotherapy decisions.

PMID- 21088131
TI  - Investing in deliberation: a definition and classification of decision support
      interventions for people facing difficult health decisions.
AB  - This article provides an analysis of 'decision aids', interventions to support
      patients facing tough decisions. Interest has increased since the concept of
      shared decision making has become widely considered to be a means of achieving
      desirable clinical outcomes. We consider the aims of these interventions and
      examine assumptions about their use. We propose three categories, interventions
      that are used in face-to-face encounters, those designed for use outside clinical
      encounters and those which are mediated, using telephone or other communication
      media. We propose the following definition: decision support interventions help
      people think about choices they face; they describe where and why choice exists;
      they provide information about options, including, where reasonable, the option
      of taking no action. These interventions help people to deliberate, independently
      or in collaboration with others, about options, by considering
      relevantattributes; they support people to forecast how they might feel about
      short, intermediate and long-term outcomes which have relevant consequences, in
      ways which help the process of constructing preferences and eventual decision
      making, appropriate to their individual situation. Although quality standards
      have been published for these interventions, we are also cautious about premature
      closure and consider that the need for short versions for use inside clinical
      encounters and long versions for external use requires further research. More
      work is also needed on the use of narrative formats and the translation of theory
      into practical designs. The interest in decision support interventions for
      patients heralds a transformation in clinical practice although many important
      areas remain unresolved.

PMID- 21088133
TI  - Transplantation of human fetal blood stem cells in the osteogenesis imperfecta
      mouse leads to improvement in multiscale tissue properties.
AB  - Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective
      tissues caused by mutations in the collagen genes. We previously showed that
      intrauterine transplantation of human blood fetal stem/stromal cells in OI mice
      (oim) resulted in a significant reduction of bone fracture. This work examines
      the cellular mechanisms and mechanical bone modifications underlying these
      therapeutic effects, particularly examining the direct effects of donor collagen
      expression on bone material properties. In this study, we found an 84% reduction
      in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells
      engrafted in bones, differentiated into mature osteoblasts, expressed
      osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The
      presence of normal collagen decreased hydroxyproline content in bones, altered
      the apatite crystal structure, increased the bone matrix stiffness, and reduced
      bone brittleness. In conclusion, expression of normal collagen from mature
      osteoblast of donor origin significantly decreased bone brittleness by improving
      the mechanical integrity of the bone at the molecular, tissue, and whole bone
      levels.

PMID- 21088132
TI  - Lymphomas differ in their dependence on Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) encodes oncogenic information and, oftentimes
      concomitant with host immunosuppression, gives rise to malignancies in all major
      categories of lymphoma defined by the World Health Organization. Here, we
      conditionally evicted the viral extrachromosomal genome from tumor cells in vitro
      to examine the role of EBV in different lymphomas, including Burkitt lymphoma
      (BL) and posttransplant lymphoproliferative disorder. Cells derived from 2
      canonical BLs were found to have the least dependence on the virus; some required
      EBV to prevent the inefficient induction of apoptosis. In contrast, cells derived
      from a subset of BL, Wp-restricted BL, required EBV to block a robust apoptotic
      program that involves the up-regulation of the proapoptotic protein Bim. Wp
      restricted BL cells also relied on the virus to promote efficient proliferation,
      a distinction that highlights the multiple contributions EBV makes to affect
      proliferation of its host cells. Like Wp-BL cells, posttransplant
      lymphoproliferative disorder cells depended on the virus to inhibit apoptosis.
      They furthermore required the virus to drive them out of G(1)/G(0). Together,
      these results reveal a graded dependence on EBV among tumor cells that directly
      correlates with the number of viral genes expressed in the tumor cell.

PMID- 21088134
TI  - CD8+ T-cell expansion and maintenance after recombinant adenovirus immunization
      rely upon cooperation between hematopoietic and nonhematopoietic antigen
      presenting cells.
AB  - We have recently reported that CD8(+) T-cell memory maintenance after
      immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon
      persistent transgene expression beyond the peak of the response. In this report,
      we have further investigated the location and nature of the cell populations
      responsible for this sustained response. The draining lymph nodes were found to
      be important for primary expansion but not for memory maintenance, suggesting
      that antigen presentation through a nonlymphoid source was required. Using bone
      marrow chimeric mice, we determined that antigen presentation by nonhematopoietic
      antigen-presenting cells (APCs) was sufficient for maintenance of CD8(+) T-cell
      numbers. However, antigen presentation by this mechanism alone yielded a memory
      population that displayed alterations in phenotype, cytokine production and
      protective capacity, indicating that antigen presentation through both
      hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8(+) T
      cell response produced by rHuAd5. These results shed new light on the
      immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8(+) T
      cell expansion and memory maintenance that relies upon both hematopoietic and
      nonhematopoietic APCs.

PMID- 21088135
TI  - B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation
      and hyperactivation and cause inflammation and autoimmunity in aged mice.
AB  - The ubiquitin-editing enzyme A20/TNFAIP3 is essential for controlling signals
      inducing the activation of nuclear factor-kappaB transcription factors.
      Polymorphisms and mutations in the TNFAIP3 gene are linked to various human
      autoimmune conditions, and inactivation of A20 is a frequent event in human B
      cell lymphomas characterized by constitutive nuclear factor-kappaB activity.
      Through B cell-specific ablation in the mouse, we show here that A20 is required
      for the normal differentiation of the marginal zone B and B1 cell subsets.
      However, loss of A20 in B cells lowers their activation threshold and enhances
      proliferation and survival in a gene-dose-dependent fashion. Through the
      expression of proinflammatory cytokines, most notably interleukin-6, A20
      deficient B cells trigger a progressive inflammatory reaction in naive mice
      characterized by the expansion of myeloid cells, effector-type T cells, and
      regulatory T cells. This culminates in old mice in an autoimmune syndrome
      characterized by splenomegaly, plasma cell hyperplasia, and the presence of class
      switched, tissue-specific autoantibodies.

PMID- 21088136
TI  - PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and
      thrombosis in a transgenic mouse model.
AB  - Heparin-induced thrombocytopenia (HIT) is a major cause of morbidity and
      mortality resulting from the associated thrombosis. Extensive studies using our
      transgenic mouse model of HIT have shown that antibodies reactive with heparin
      platelet factor 4 complexes lead to FcgammaRIIA-mediated platelet activation in
      vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318
      (PRT318), a novel selective inhibitor of the tyrosine kinase Syk, as an approach
      to HIT treatment. PRT318 completely inhibited HIT immune complex-induced
      aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT
      model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and
      heparin. The experimental group received orally dosed PRT318, whereas the control
      group received vehicle. Nadir platelet counts of PRT318-treated mice were
      significantly higher than those of control mice. When examined with a novel
      thrombosis visualization technique, mice treated with PRT318 had significantly
      reduced thrombosis. The Syk inhibitor PRT318 thus prevented both HIT immune
      complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its
      activity in HIT.

PMID- 21088137
TI  - Genomic profiling combined with gene expression profiling in primary central
      nervous system lymphoma.
AB  - Of the genetic changes in primary central nervous system lymphoma (PCNSL), little
      is known. To detect copy number alterations and differentially expressed genes in
      PCNSL, we analyzed a total of 12 PCNSL samples with high-resolution array-based
      comparative genomic hybridization and performed expression profiling in 7 of the
      12 samples. The most frequent deletion found in 8 patients (66.7%) occurred in
      9p21.3 containing CDKN2A. We compiled the top 96 genes (family-wise error rate, P
      < .05) showing the greatest differential expression between PCNSL and normal
      lymph node tissues. From these, we selected 8 candidate genes (NPFFR2, C4orf7,
      OSMR, EMCN, TPO, FNDC1, COL12A1, and MSC) in which expression changes were
      associated with copy number aberrations. All 8 genes showed both down-regulation
      in expression microarray and deletion in array-based comparative genomic
      hybridization analyses. These genes participate in cell signaling or cell
      adhesion. In addition, low mRNA expression of C4orf7 was significantly associated
      with poor survival (P = .0425). Using gene set enrichment analysis, we identified
      several signal transduction pathways, such as Janus kinase-signal transducers and
      activators of transcription pathway and adhesion-related pathways, which may be
      involved in pathogenesis of PCNSL. In conclusion, this study identified novel
      tumor suppressor genes that may serve as therapeutic targets of PCNSL.

PMID- 21088138
TI  - Platelets suppress Treg recruitment.

PMID- 21088139
TI  - Dismounting the MDR horse.

PMID- 21088140
TI  - Tracing C/EBPalpha+ cells and their progeny.

PMID- 21088141
TI  - Abnormalities in Th17 T cells in aplastic anemia.

PMID- 21088142
TI  - Micro-mismanaging sickle cell stress.

PMID- 21088143
TI  - Size matters for polyP to clot.

PMID- 21088144
TI  - Podoplanin-Fc burns out platelets.

PMID- 21088145
TI  - N-acetyl cysteine protects TMJ chondrocytes from oxidative stress.
AB  - Temporomandibular joint (TMJ) inflammation is closely associated with oxidative
      stress. This study tested the potential of N-acetyl cysteine (NAC), an anti
      oxidant amino-acid derivative, in alleviating oxidative stress-related damage in
      TMJ chondrocytes. The inflammatory condition was simulated by the addition of
      hydrogen peroxide (H2O2) to TMJ-derived chondrocyte cultures. Exposure to H2O2
      decreased the cell population by half within 2 days as a result of induced
      apoptosis and reduced proliferation. Gene expression of aggrecan and collagen II,
      as well as glycosaminoglycan production, were reduced by more than 70%. These
      compromised chondrocyte viability and function were fully restored by the
      addition of NAC to the cultures. NAC reduced the H2O2-elevated intracellular
      reactive oxygen species to the normal level and increased cellular glutathione
      reserves. These results indicate that NAC restores oxidative stress-induced cell
      death and severe functional impairment in TMJ chondrocytes, and warrant in vivo
      testing to explore its therapeutic potential as an anti-inflammatory agent.

PMID- 21088146
TI  - Proteases of an early colonizer can hinder Streptococcus mutans colonization in
      vitro.
AB  - Streptococcus mutans is the primary cariogen that produces several virulence
      factors that are modulated by a competence-stimulating peptide (CSP) signaling
      system. In this study, we sought to determine if proteases produced by early
      dental plaque colonizers such as Streptococcus gordonii interfere with the
      subsequent colonization of S. mutans BM71 on the existing streptococcal biofilms.
      We demonstrated that S. mutans BM71 colonized much less efficiently in vitro on
      streptococcal biofilms than on Actinomyces naeslundii biofilms. Several oral
      streptococci, relative to A. naeslundii, produced proteases that inactivated the
      S. mutans CSP. We further demonstrated that cell protein extracts from S.
      gordonii, but not from A. naeslundii, interfered with S. mutans BM71
      colonization. In addition, S. mutans BM71 colonized more efficiently on the sgc
      protease knockout mutant of S. gordonii than on the parent biofilms. In
      conclusion, proteases of early colonizers can interfere with subsequent
      colonization by S. mutans in vitro.

PMID- 21088147
TI  - Development and validation of a simple cell-based fluorescence assay for
      dipeptidyl peptidase 1 (DPP1) activity.
AB  - Dipeptidyl peptidase 1 (DPP1) (EC 3.4.14.1; also known as cathepsin C, cathepsin
      J, dipeptidyl aminopeptidase, and dipeptidyl aminotransferase) is a lysosomal
      cysteinyl protease of the papain family involved in the intracellular degradation
      of proteins. Isolated enzyme assays for DPP1 activity using a variety of
      synthetic substrates such as dipeptide or peptide linked to amino-methyl-coumarin
      (AMC) or other fluorophores are well established. There is, however, no report of
      a simple whole-cell-based assay for measuring lysosomal DPP1 activity other than
      the use of flow cytometry (fluorescence-activated cell sorting) or the use of
      invasive activity-based probes or the production of physiological products such
      as neutrophil elastase. The authors investigated a number of DPP1 fluorogenic
      substrates that have the potential to access the lysosome and enable the
      measurement of DPP1 enzyme activity in situ. They describe the development and
      evaluation of a simple noninvasive fluorescence assay for measuring DPP1 activity
      in fresh or cryopreserved human THP-1 cells using the substrate H-Gly-Phe-AFC
      (amino-fluoro-coumarin). This cell-based fluorescence assay can be performed in a
      96-well plate format and is ideally suited for determining the cell potency of
      potential DPP1 enzyme inhibitors.

PMID- 21088148
TI  - Molecular and immunohistologic analyses cannot reliably solve diagnostic
      variation of flat intraepithelial lesions of the urinary bladder.
AB  - We examined diagnostic variation of flat intraurothelial lesions with comparison
      with immunohistochemical and fluorescence in situ hybridization (FISH) analyses.
      Nine uropathologists diagnosed 23 biopsy samples from the urinary bladder. The
      samples were analyzed by immunohistochemical expression of cytokeratin 20, high
      molecular-weight cytokeratin, Ki-67, p53, and p16(INK4a), and multicolor FISH
      using the UroVysion probe set (Vysis, Abbott, Des Plaines, IL). Diagnostic
      agreement for each classification and for nonneoplastic or neoplastic lesions was
      obtained in 8 (35%) and 16 (70%) of 23 lesions, respectively. The preference
      ratio of neoplasia to nonneoplasia (0.9 to 4.8) or carcinoma in situ to dysplasia
      (0.2 to 4.0) also varied among the pathologists. In 6 ancillary analyses, the
      majority of neoplastic lesions with diagnostic agreement indicated more than 2
      aberrant results, whereas the majority of lesions without diagnostic agreement
      showed no or only 1 aberrant result. The molecular and immunohistochemical
      analyses can discriminate between neoplastic and nonneoplastic lesions; however,
      they cannot reliably solve diagnostic variation of flat intraepithelial lesions.

PMID- 21088149
TI  - Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type
      and grade.
AB  - Carbonic anhydrase IX (CAIX), a hypoxia-induced protein, is expressed in some
      renal tumors. We evaluated its immunohistochemical expression in 317 primary and
      42 metastatic renal neoplasms (186 clear cell, 52 papillary, 35 chromophobe, 47
      unclassified, and 15 Xp11.2 translocation renal cell carcinomas [RCCs]; 26
      oncocytomas; 2 metanephric adenomas; 1 urothelial carcinoma; 1 mixed epithelial
      and stromal tumor; and 1 angiomyolipoma); 7 neoplasms were unknown as to whether
      they were primary or metastatic. We also correlated expression with tumor type
      and grade. Variable staining was seen in clear cell, papillary, unclassified, and
      Xp11.2 translocation carcinomas. One chromophobe carcinoma had focal expression.
      No staining was seen with other tumors. An association was found between high
      expression and clear cell vs non-clear cell carcinomas with all cases (P < .01)
      and primary (P < .01) cases. An association between CAIX expression and grade (P
      < .01) in primary clear cell carcinomas was found. CAIX expression is more common
      in clear cell RCC than other renal tumor types and is associated with grade.

PMID- 21088150
TI  - Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma.
AB  - HER2 overexpression and amplification have been studied as a therapeutic and
      prognostic target in a number of human cancers, including esophageal, gastric,
      and colorectal adenocarcinomas. However, HER2 status has not been well
      investigated in primary small intestinal adenocarcinoma, probably because of its
      rarity. In this study, we conducted immunohistochemical analysis and fluorescence
      in situ hybridization (FISH) for HER2 on 49 primary nonampullar small intestinal
      adenocarcinomas. The results showed a complete lack of HER2 protein expression in
      47 cases (96%) by immunohistochemical analysis. Only 2 cases (4%) showed a 1+
      staining pattern. No tumors exhibited 2+ or 3+ HER2 immunoreactivity. By FISH,
      none of the tumors, including those with 1+ HER2 immunoreactivity, exhibited HER2
      gene amplification. These observations demonstrate that HER2 protein
      overexpression and gene amplification are infrequent events, if they occur at
      all, in small intestinal adenocarcinoma. Thus, routine immunohistochemical and/or
      FISH testing for HER2 for potential targeted anti-HER2 therapy may not be
      beneficial for patients with primary small intestinal adenocarcinoma.

PMID- 21088151
TI  - Aseptic lymphocyte-dominated vasculitis-associated lesion: a clinicopathologic
      review of an underrecognized cause of prosthetic failure.
AB  - It is estimated that 35% of total hip arthroplasties (THAs) involve a second
      generation metal-on-metal (MOM) prosthesis. A novel complication has appeared in
      a subset of patients with MOM THAs that is described as an aseptic, lymphocyte
      dominated vasculitis-associated lesion (ALVAL). The clinical features of ALVAL
      are nonspecific, but patients complain of pain and may develop "pseudotumors." It
      is hypothesized that metal ions are released from the prosthesis and form haptens
      with native proteins that elicit a type IV hypersensitivity response in the local
      soft tissues. Histopathologic descriptions of ALVAL are similar to those of
      failed arthroplasty in general, with the addition of a dense perivascular
      inflammatory infiltrate that is the hallmark of ALVAL. We report 3 cases of ALVAL
      with clinical, radiographic, and histologic findings. Accurate assessment is
      crucial because an intraoperative diagnosis of chronic inflammation suggestive of
      ALVAL will necessitate a replacement of the prosthetic component surfaces.

PMID- 21088152
TI  - Aspiration cytomorphology of fetal adenocarcinoma of the lung.
AB  - Fetal adenocarcinoma (FA) of the lung is an exceedingly rare malignancy. Many
      patients with the well-differentiated form are relatively young and with the high
      grade variant are older. We describe the cases of 4 women with FA examined by
      fine-needle aspiration biopsy. Aspirates were moderately cellular with malignant,
      mostly aggregated cells. Glands and acini were present. The columnar neoplastic
      epithelial cells had homogeneous round nuclei with fine chromatin, smooth
      membranes, and indistinct nucleoli. With the rapid Romanowsky stain, subnuclear
      vacuoles were evident in some tumor cells; at times, this was associated with a
      focal extracellular tigroid pattern. Morule formation was present in the 3
      specimens. Immunochemically, all tumors manifested epithelial and neuroendocrine
      differentiation. Cytomorphologic attributes included the following: (1) distinct
      subnuclear vacuoles, sometimes with an associated tigroid picture; (2) small,
      uniform, round nuclei; (3) morules; and (4) neuroendocrine differentiation in
      glandular epithelial cells.

PMID- 21088153
TI  - A new approach for identifying patients with ovarian epithelial neoplasms based
      on high-resolution mass spectrometry.
AB  - We investigated the serum profiles of patients with ovarian neoplasm using high
      performance liquid chromatography (HPLC) and high-resolution mass spectrometry
      (HRMS) to obtain serum "fingerprints" for use in identifying patients with these
      neoplasms. We used HPLC-HRMS to analyze serum samples from patients with ovarian
      neoplasms and control subjects. Serum samples from 145 patients were analyzed,
      including 85 with ovarian epithelial neoplasms. We also compared the results of
      this serum-fingerprinting approach with the results of the CA-125 test and
      imaging. Fingerprinting successfully permitted the separation of control patients
      and patients with ovarian neoplasms. The sensitivity and specificity of the test
      were between 96% and 100%. When the results of this test were concordant with the
      results of the CA-125 test, 99% of serum samples were correctly classified as
      being from a patient with an ovarian neoplasm or with no ovarian neoplasm. We
      found that a metabolite of molecular weight 472 is the main metabolite in the
      separation of patients with ovarian neoplasms from control subjects. HPLC-HRMS
      serum profiling could become a screening test for ovarian neoplasms.

PMID- 21088154
TI  - Rapid identification of 2009 H1N1 influenza A virus using fluorescent antibody
      methods.
AB  - Identification of the 2009 H1N1 influenza A virus requires emergency use
      authorized (EUA) molecular reverse transcriptase-polymerase chain reaction.
      Laboratories lacking molecular capabilities outsource testing, which is costly
      and may delay result reporting. A fluorescent antibody (FA; D(3) Ultra 2009 H1N1
      influenza A virus ID Kit, Diagnostic Hybrids, Athens, OH) recently received Food
      and Drug Administration EUA status for 2009 H1N1 virus identification. The
      performance of this FA reagent was evaluated in this study. Influenza A-positive
      nasopharyngeal specimens (seasonal H1, H3, and 2009 H1N1) were prepared for
      culture and FA testing and were stained using influenza A antibodies and the 2009
      H1N1 reagent. Other respiratory viruses were also evaluated. The FA reagent
      demonstrated 100% sensitivity and specificity. Bright, apple-green fluorescence
      was effortlessly identified in culture-positive cells, particularly around cell
      membrane perimeters. Laboratory-prepared slides were preferred over bedside
      prepared specimens because background fluorescence obscured identification in the
      latter. The new FA reagent provides an accurate, rapid, and inexpensive assay for
      identifying the 2009 H1N1 virus in nonmolecular diagnostic laboratories.

PMID- 21088155
TI  - Viral drug sensitivity testing using quantitative PCR: effect of tyrosine kinase
      inhibitors on polyomavirus BK replication.
AB  - Our objective was to determine whether quantitative polymerase chain reaction
      (PCR) can be used to measure the effect of tyrosine kinase (TK) inhibition on
      polyomavirus BK (BKV) replication. The BKV was grown in a cell culture system.
      The rate of viral replication in the presence or absence of the drug being tested
      was assessed by amplifying the viral genome using primers directed against the
      viral capsid 1 protein. Dasatinib, erlotinib, gefitinib, imatinib, sunitinib, and
      sorafenib all showed antiviral activity at micromolar concentrations. The 50%
      effective concentration for erlotinib and sorafenib was within blood
      concentrations readily achieved in human subjects. Quantitative PCR is a
      convenient method for viral drug sensitivity testing for slow-growing viruses
      that do not readily produce cytopathic effect. TK inhibitors deserve further
      consideration as a potential therapeutic option for BKV-associated nephropathy
      and hemorrhagic cystitis.

PMID- 21088156
TI  - Identification of two borderline oxacillin-resistant strains of Staphylococcus
      aureus from routine nares swab specimens by one of three chromogenic agars
      evaluated for the detection of MRSA.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of
      nosocomial infections that result in extended hospital stays and increased
      mortality. Therefore, rapid, cost-effective techniques for surveillance and
      detection of MRSA are critical to the containment and prevention of the spread of
      MRSA within the health care environment. We examined the ability of 3 chromogenic
      media (Spectra MRSA, Remel, Lenexa, KS; MRSA Select, Bio-Rad, Redmond, WA; and
      ChromID MRSA, bioMerieux, Marcy l'Etoile, France) to detect MRSA from routine
      surveillance specimens following 18, 24, and 48 hours of incubation. Our results
      indicate that detection of MRSA using all 3 chromogenic media is optimal
      following 24 hours of incubation. Early examination reduced sensitivity, while
      extended incubation reduced specificity. In addition, Spectra MRSA identified 2
      borderline oxacillin-resistant strains of S aureus that were not detected by the
      other 2 chromogenic agars evaluated. These strains demonstrate increased basal
      and inducible resistance to beta-lactam antibiotics.

PMID- 21088157
TI  - Performance characteristics of six intact parathyroid hormone assays.
AB  - The aim of this study was to evaluate the performance characteristics of 6 intact
      parathyroid hormone assays: Access 2 (Beckman Coulter, Fullerton, CA), ARCHITECT
      i2000(SR) (Abbott Diagnostics, Abbott Park, IL), ADVIA Centaur (Siemens
      Healthcare Diagnostics, Deerfield, IL), Modular E170 (Roche Diagnostics,
      Indianapolis, IN), IMMULITE 2000 (Siemens Healthcare Diagnostics), and LIAISON
      (DiaSorin, Stillwater, MN). Sample collection tubes and storage conditions were
      compared. Imprecision studies were performed using commercial quality control
      materials. Linearity was assessed using pools prepared from samples. For method
      comparison, serum and EDTA plasma samples were tested by all methods, and the
      ARCHITECT was used as the comparison method. Reference intervals were determined
      using various vitamin D cutoffs. The types of collection tubes and storage
      conditions are more important for some methods than others. Total coefficients of
      variation were 10.9% or less. The maximum deviation from the target recovery for
      linearity ranged from 5.0% to 82.2%. Bland-Altman plots demonstrated percentage
      biases ranging from -36.3% to 24.4%. The lower limit of the reference interval
      was not influenced by vitamin D status, whereas the upper reference limit was
      affected.

PMID- 21088158
TI  - Use of likelihood ratios improves interpretation of laboratory testing for
      pulmonary sarcoidosis.
AB  - Laboratory tests for pulmonary sarcoidosis (percentage lymphocytes and CD4/CD8
      ratio in bronchoalveolar lavage fluid and serum angiotensin-converting enzyme
      activity) lack sensitivity and specificity. In a retrospective study of 153
      subjects under suspicion of pulmonary sarcoidosis (36 cases and 117 patients with
      other diseases [control patients]), we defined likelihood ratios (LRs) for
      rationally selected result intervals of these tests, which improve clinical
      interpretation as compared with dichotomous interpretation based on a single
      cutoff value. By using logistic regression analysis, we further integrated the 3
      individual tests into a unified algorithm that could rule out diagnosis in 57
      (48.7%) of the 177 control subjects and confirm diagnosis in 12 (33%) of the 36
      pulmonary sarcoidosis cases. We conclude that use of LRs improves interpretation
      of laboratory tests for pulmonary sarcoidosis. In addition, we present a
      prediction algorithm based on the combination of laboratory tests that helps
      clinicians confirm or exclude diagnosis in almost half of the study population.

PMID- 21088159
TI  - Evaluation of heparin assay for coagulation management in newborns undergoing
      ECMO.
AB  - The objective was to identify the usefulness of heparin level by anti-factor Xa
      (anti-Xa) assay vs activated partial thromboplastin time (PTT) or activated
      clotting time (ACT) in neonates undergoing extracorporeal membrane oxygenation
      (ECMO). A retrospective record review of 21 patients in the neonatal intensive
      care unit (mean ECMO initiation age, 2 days; range, 0-4 days; male/female ratio,
      1:1) undergoing ECMO from 2006 to 2008 was performed. Linear regression
      correlations between anti-Xa, PTT, and ACT were determined by extrapolating PTT
      and ACT therapeutic ranges that corresponded with the ECMO heparin target range
      of 0.3 to 0.6 U/mL. Pearson correlation coefficients between heparin levels and
      PTT (-0.903 to 0.984), PTT less than 40 seconds after correction using PTT
      heparinase (-0.903 to 1.000), and ACT (-0.951 to 0.891) in this patient
      population were widely variable. Inconsistency of PTT and ACT therapeutic ranges
      corresponding to heparin levels of 0.3 to 0.6 U/mL prompts a multifactorial
      approach to ECMO management because no single laboratory test can be used to
      determine appropriate anticoagulation management.

PMID- 21088160
TI  - Development of North American consensus guidelines for medical laboratories that
      perform and interpret platelet function testing using light transmission
      aggregometry.
AB  - Platelet function testing is important for the diagnostic evaluation of common
      and rare bleeding disorders. Our study goals were to promote best practices and
      reduce unnecessary testing variances by developing North American guidelines on
      platelet function testing. Guidelines were developed by consensus for expert
      recommendations (minimum level for approval, 70%) that included recommendations
      on the evaluation and interpretation of light transmission platelet aggregometry
      (LTA). To assess consensus, medical opinions on recommendations were gathered
      from diagnostic laboratories that perform LTA, in collaboration with the Quality
      Management Program-Laboratory Services (QMP-LS) in Ontario, Canada (10
      laboratories), and the North American Specialized Coagulation Laboratory
      Association (NASCOLA; 47 laboratories, 5 overlapping the QMP-LS group). Adequate
      consensus was achieved for all and 89% of recommendations for the QMP-LS and
      NASCOLA groups, respectively. The recommendations adopted provide North American
      laboratories with additional guidance on platelet function testing, including how
      to interpret LTA abnormalities.

PMID- 21088161
TI  - Increases in quantitative D-dimer levels correlate with progressive disease
      better than circulating tumor cell counts in patients with refractory prostate
      cancer.
AB  - Changes in quantitative D-dimer levels, circulating tumor cell (CTC) counts, and
      prostate-specific antigen (PSA) levels were measured in 28 patients with
      refractory castration-resistant prostate cancer to assess their concordance
      during the course of therapy and their relationship with risk of progressive
      disease. A significant correlation was identified between changes in PSA and both
      CTC counts and D-dimer levels (r = 0.67 and 0.58, respectively; P < .001). In
      addition, there was a significant correlation between changes in CTC count and D
      dimer level (r = 0.62; P < .001). A significantly stronger concordance between
      these biomarkers was noted for increasing values (sensitivity, 72%-77.8%)
      compared with decreasing values (specificity, 43.8%-71.4%). Notably, increases in
      PSA and D-dimer levels, not CTC counts, were associated with increased risks for
      progressive disease (P < .024). Increases in quantitative D-dimer levels
      correlate with progressive disease better than CTC counts in patients with
      refractory prostate cancer.

PMID- 21088162
TI  - Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene
      rearrangement.
AB  - Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade
      lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We
      present the first report of a case of FL that transformed to plasmablastic
      lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical
      IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/
      BCL2 translocation was retained in the PBL, which also acquired c-myc gene
      rearrangement. Genealogic analysis based on somatic hypermutation of the
      rearranged IGH genes of both FL and PBL suggests that transformation of the FL to
      PBL occurred most likely by divergent evolution from a common progenitor cell
      rather than direct evolution from the FL clone. Our study of this unusual case
      expands the histologic spectrum of FL transformation and increases our
      understanding of the pathogenetic mechanisms of transformation of indolent
      lymphomas to aggressive lymphomas.

PMID- 21088163
TI  - Necessity of bilateral bone marrow biopsies for ancillary cytogenetic studies in
      the pediatric population.
AB  - The need for bilateral pediatric bone marrow biopsies for cytogenetic and
      fluorescent in situ hybridization (FISH) studies has not been clearly delineated.
      We retrospectively identified 166 pediatric bilateral bone marrow biopsy
      specimens obtained from patients with a variety of clinical diagnoses, including
      solid tumors, lymphoma, leukemia, and other hematologic conditions. The cases
      included all pediatric bilateral bone marrow biopsies performed at our hospital
      spanning the years of 1992 to 2008. Agreement of FISH and classical cytogenetic
      results between the 2 sides was assessed. Of a total of 166 bilateral cases, 2
      cases showed disagreement (1.2%), both from patients with solid tumors. One case
      was a rhabdomyosarcoma, in which FISH only was performed; the second was a
      neuroblastoma in which FISH and cytogenetics were performed (both FISH and
      classical cytogenetic results disagreed). The remainder of the cases showed
      complete agreement between the 2 sides (total 98.8%). We conclude that it is
      usually not necessary to perform bilateral bone marrow biopsies for FISH and
      cytogenetics in the pediatric population outside of the setting of solid tumor
      staging.

PMID- 21088165
TI  - Enhanced pathologic analysis for pericolonic tumor deposits: is it worth it?

PMID- 21088166
TI  - Atypical transmissible spongiform encephalopathies in ruminants: a challenge for
      disease surveillance and control.
AB  - Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel
      disease in cattle, enormous efforts were undertaken to monitor and control the
      disease in ruminants worldwide. The driving force was its high economic impact,
      which resulted from trade restrictions and the loss of consumer confidence in
      beef products, the latter because BSE turned out to be a fatal zoonosis, causing
      variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal
      in livestock feed and the removal of specified risk materials from the food chain
      were the main measures to successfully prevent infection in cattle and to protect
      human beings from BSE exposure. However, although BSE is now under control,
      previously unknown, so-called atypical transmissible spongiform encephalopathies
      (TSEs) in cattle and small ruminants have been identified by enhanced disease
      surveillance. This report briefly reviews and summarizes the current level of
      knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the
      question of the extent to which such atypical TSEs have an effect on disease
      surveillance and control strategies.

PMID- 21088167
TI  - Diagnostic assays used to control small ruminant lentiviruses.
AB  - The serologic diagnostic tests, such as the agar gel immunodiffusion assay and
      various types of enzyme-linked immunosorbent assays (ELISAs), have contributed to
      the reduction of small ruminant lentivirus (SRLV) infections worldwide. Because
      there are no treatments or efficacious vaccines, the serologic diagnostic tests
      have supported most of the eradication efforts by testing and removal or
      separation of adult animals that generate antibodies to SRLVs. With the advent of
      molecular diagnostics, standard and quantitative polymerase chain reaction (PCR)
      based assays for the detection of provirus in peripheral blood cells are becoming
      more common and aid in the detection of infected goats and sheep before antibody
      detection by ELISA in some animals. Performance of the serologic and molecular
      diagnostic tests is dependent upon a number of factors, including the format of
      the assay, the percentage of identity between the viral nucleotide sequences in a
      flock or herd of a certain geographic region and the sequences used to generate
      SRLV test reagents, and the intrinsic pathogenesis or amount of provirus and SRLV
      antibody generated in a species or individual small ruminant. In addition, small
      ruminant genomics may help with establishing genetic markers of SRLV infection
      and disease, which could also aid eradication or reduction of SRLVs from herds
      and flocks throughout the world.

PMID- 21088168
TI  - Development, validation, and utilization of a competitive enzyme-linked
      immunosorbent assay for the detection of antibodies against Brucella species in
      marine mammals.
AB  - A competitive enzyme-linked immunosorbent assay (cELISA) was developed by using a
      whole-cell antigen from a marine Brucella sp. isolated from a harbor seal (Phoca
      vitulina). The assay was designed to screen sera from multiple marine mammal
      species for the presence of antibodies against marine-origin Brucella. Based on
      comparisons with culture-confirmed cases, specificity and sensitivity for
      cetacean samples tested were 73% and 100%, respectively. For pinniped samples,
      specificity and sensitivity values were 77% and 67%, respectively. Hawaiian monk
      seal (Monachus schauinslandi; n  =  28) and bottlenose dolphin (Tursiops
      truncatus; n  =  48) serum samples were tested, and the results were compared
      with several other assays designed to detect Brucella abortus antibodies. The
      comparison testing revealed the marine-origin cELISA to be more sensitive than
      the B. abortus tests by the detection of additional positive serum samples. The
      newly developed cELISA is an effective serologic method for detection of the
      presence of antibodies against marine-origin Brucella sp. in marine mammals.

PMID- 21088169
TI  - Atypical scrapie/Nor98 in a sheep from New Zealand.
AB  - In a consignment of sheep brains from New Zealand, to be used in Europe as
      negative control material in scrapie rapid screening test evaluations, brain
      samples from 1 sheep (no. 1512) gave the following initially confusing results in
      various screening tests: the brainstem repeatedly produced negative results in 2
      very similar screening kits (enzyme-linked immunosorbent assay [ELISA]-1, ELISA
      2), a macerate made from brainstem and cerebellum returned a clearly positive
      result in ELISA-2, and the macerate and a brainstem sample gave negative results
      in a third screening test (ELISA-3). In subsequent testing, cerebellum tissue
      alone tested strongly positive in ELISA-1 and produced a banding pattern very
      similar to atypical scrapie/Nor98 in a confirmatory Western blot (WB). The
      macerate showed weak staining in the confirmatory WB but presented a staining
      pattern identical to atypical scrapie/Nor98 in the scrapie-associated fibril WB.
      The latter test confirmed conclusively the first case of atypical scrapie/Nor98
      in a sheep from New Zealand. Other parts of the brain either tested negative or
      very weak positive in ELISA-2 and in WBs, or tested with negative results by
      histopathology and immunohistochemistry. It appears that sheep no. 1512 is a case
      of atypical scrapie/Nor98 in which the abnormal prion protein was detected mainly
      in the cerebellum. This case emphasizes the need to retain brainstem, and
      cerebral and cerebellar tissues, as frozen and fixed materials, for conclusive
      confirmatory testing. Furthermore, consideration should be given to which
      screening method to use.

PMID- 21088170
TI  - Inflammatory myopathy with severe tongue atrophy in Pembroke Welsh Corgi dogs.
AB  - A disease characterized by tongue and facial muscle atrophy has been recognized
      sporadically among Pembroke Welsh Corgi (PWC) dogs in Japan. The present study
      describes the pathologic findings of this canine syndrome. Histopathologic
      examinations were performed in 2 dogs, including a case of muscular biopsy.
      Identification and characterization of autoantibodies were attempted by
      fluorescent antibody test (FAT) and Western blot (WB) by using sera from 7 PWC
      dogs with typical clinical features, 6 PWC dogs with other clinical signs, and 2
      from other breeds with polymyositis. Clinically, the 7 affected PWC dogs
      exhibited dysphagia with severe tongue atrophy, facial muscular atrophy, and
      occasional walking difficulty. Histopathologic examinations of the 2 dogs with
      clinical symptoms revealed moderate to severe inflammatory lesions characterized
      by lymphohistiocytic infiltration and muscular atrophy in the tongue and/or
      femoral muscles. The tongue lesions were very severe and accompanied by diffuse
      fatty infiltration. There were no major lesions in the nervous tissues examined.
      By FAT, an autoantibody against the cross striation of skeletal muscle was
      detected in sera from 5 affected PWC dogs. By using WB analysis, the
      autoantibodies recognized a 42-kDa molecule in striated muscle but not in the
      nervous tissues. All of the findings indicated that the unique disease of PWC
      dogs might be generalized inflammatory myopathy, whereas the detailed etiology
      concerning the dominant involvement of tongue muscles and the role of the
      autoantibody in the canine disease remain to be clarified.

PMID- 21088171
TI  - Detection of infectious pancreatic necrosis virus in subclinically infected
      Atlantic salmon by virus isolation in cell culture or real-time reverse
      transcription polymerase chain reaction: influence of sample preservation and
      storage.
AB  - Infectious pancreatic necrosis, an important problem of the salmon industry
      worldwide, is caused by Infectious pancreatic necrosis virus (IPNV). Fish
      surviving an IPNV infection become virus carriers, and the identification of
      infected fish is highly relevant to disease control. The target organ for IPNV
      diagnosis is the kidney, where the virus persists, usually with low virus loads.
      The current study documents a real-time reverse transcription polymerase chain
      reaction (real-time RT-PCR) assay that proved 100 times more sensitive than a
      conventional RT-PCR. Cell culture and real-time RT-PCR were compared for their
      ability to detect IPNV in carrier Atlantic salmon kidney samples after different
      preservation and storage procedures. Storage of whole tissue at -80 degrees C for
      1 month and storage of tissue homogenized in transport medium (TM) at +4 degrees
      C for 1 week before investigation in cell cultures resulted in a marked reduction
      of virus infectivity. For detection by real-time RT-PCR, storage of whole tissue
      was suboptimal, whereas storage of tissue homogenized in TM did not affect virus
      detection. The results of the present study demonstrate that both cell culture
      and real-time RT-PCR are reliable tests for the detection of low amounts of IPNV
      in kidneys of carrier Atlantic salmon, and both methods are relatively robust
      against minor preservation and storage deviations, or both. Preservation of
      tissues in RNA stabilization solution seems only necessary when samples are to be
      shipped at ambient temperatures or when laboratory testing might be delayed.
      Independent of detection method, these results indicate that for long-term
      storage, samples are best kept at -80 degrees C after homogenization in TM.

PMID- 21088172
TI  - Effect of sampling method and storage conditions on albumin, retinol-binding
      protein, and N-acetyl-beta-D-glucosaminidase concentrations in canine urine
      samples.
AB  - Urinary markers for renal dysfunction are gaining interest, but effects of
      sampling method, storage conditions, and urinary tract inflammation or infection
      on these markers are unclear. Therefore, the objectives of the current study were
      to determine the difference in urinary albumin (uALB), urinary retinol-binding
      protein (uRBP), and urinary N-acetyl-beta-D-glucosaminidase (uNAG) concentrations
      in cystocentesis and voided samples and to investigate concentration changes
      after storage at -20 degrees C and at -80 degrees C. Effects of a protease
      inhibitor were also assessed in samples stored at -80 degrees C for 12 months. In
      a pilot experiment, influence of in vitro hematuria, pyuria, and bacteriuria on
      the urinary markers was evaluated. A mixed model was used to calculate mean
      differences and 95% confidence intervals. Urinary ALB, uNAG, and uRBP
      concentrations were similar in voided and cystocentesis samples. After storage
      for 4 months at -20 degrees C, uALB concentration was not affected, and uRBP
      concentration showed a mild and clinically irrelevant decrease, whereas uNAG
      activity was significantly lower compared with fresh samples. After storage for
      12 months at -80 degrees C, uALB and uRBP concentrations did not differ from
      fresh samples, but uNAG activity was severely decreased. Protease inhibitor
      addition did not preserve uNAG activity. Experimental hematuria, pyuria, and
      bacteriuria did not seem to affect urinary markers, although further research is
      needed.

PMID- 21088173
TI  - Comparison of blood lead and blood and plasma delta-aminolevulinic acid
      concentrations as biomarkers for lead poisoning in cattle.
AB  - Lead (Pb) concentrations in whole blood and delta-aminolevulinic acid (ALA)
      concentrations in plasma and whole blood from 37 cattle with suspected Pb
      exposure were determined in order to investigate the usefulness of ALA as a
      biological indicator for Pb poisoning in cattle. Cows were divided into 4 groups
      based on blood Pb, as follows: <30 ppb (group 1), 30-100 ppb (group 2), 100-300
      ppb (group 3), and >300 ppb (group 4). The derivatization reaction for ALA was
      improved by a greater than 2-fold measure in whole blood and by a 10-fold measure
      in plasma by adding 75 and 50 ul of 0.1 N HCl, respectively. Blood Pb
      concentrations ranged from <25 ppb to 1,006 ppb (185.5 +/- 254.9 ppb), with 17
      samples containing >50 ppb Pb. Delta-aminolevulinic acid concentrations in whole
      blood and plasma ranged from <62.7 ppb to 96.9 ppb (77.4 +/- 8.4 ppb) and from
      <5.0 ppb to 24.0 ppb (4.6 +/- 3.8 ppb), respectively. Whole blood ALA did not
      correlate with blood lead concentrations in any group. Increase in plasma ALA
      concentration was dependent on blood Pb concentration. There was no correlation
      between blood Pb concentration and plasma ALA concentration in group 2 (n  =  4),
      but correlation coefficients were 0.736 in group 3 and 0.807 in group 4,
      respectively. The correlation coefficient was increased to 0.851 when groups 3
      and 4 were combined. Based on these observations, in cattle, plasma ALA is a more
      reliable biological biomarker for Pb exposure than is blood ALA.

PMID- 21088174
TI  - Bi-antigenic immunoassay models based on the recombinant PvpA proteins for
      Mycoplasma gallisepticum diagnosis in chickens.
AB  - The present study aimed to produce the relatively conserved central fragment of
      the Mycoplasma gallisepticum PvpA cytadhesin as recombinant antigen and to
      determine its species-specific diagnostic potential in comparison with the full
      length recombinant rPvpA336 protein. For this purpose, a recombinant protein
      (rPvpA134) consisting of 134 amino acids with apparent molecular mass of 27 kD
      was produced and highly purified. The rPvpA134 protein was composed of the amino
      acid residues at positions 133-265 with respect to the wild-type PvpA. Two bi
      antigenic diagnostic models based on Western blot and enzymatic rapid
      immunofiltration assay (ERIFA) were developed to compare simultaneously the
      diagnostic potential of the recombinant antigens rPvpA134 and rPvpA336. Although
      40% of the confirmed rPvpA336-positive chicken sera were detected as reactive
      with rPvpA134, this protein would be a useful secondary diagnostic antigen with
      which to confirm species-specific antibody response for monitoring M.
      gallisepticum infections. It can be concluded from the present study that 2 bi
      antigenic models were successfully adapted to the specific diagnosis of chicken
      M. gallisepticum. Furthermore, by virtue of its simplicity and rapidity, the
      ERIFA model has multi-antigenic application potential, making it an alternative
      field test that is widely applicable in the veterinary diagnostic field.

PMID- 21088175
TI  - A diagnostic algorithm for detection of antibodies to influenza A viruses in dogs
      in Italy (2006-2008).
AB  - Since 2004, there have been several reports of Influenza A virus (FLUAV)
      infection in dogs. Dogs have been infected with equine influenza H3N8, avian
      influenza H3N2 and H5N1, and the pandemic H1N1 virus. Because of recent avian and
      equine influenza outbreaks in Italy, the objectives of the present study were to
      estimate the level of exposure of Italian dogs to influenza A viruses and to
      assess a diagnostic algorithm for detection of FLUAV exposure in dogs. Sera
      collected from 6,858 dogs from 2006 to 2008 were screened in a competitive enzyme
      linked immunosorbent assay (cELISA) for antibodies to the highly conserved
      influenza A nucleoprotein. Samples positive in the cELISA were confirmed by
      testing in hemagglutination inhibition (HI) and fluorescent antibody test (FAT).
      Two seropositive dogs had antibodies to H3 hemagglutinin proteins, consistent
      with exposure to recent canine and equine subtype H3N8 viruses. Using a Bayesian
      model, the sensitivity and specificity of the cELISA were estimated as 93.98%
      (probability intervals [PI]: 81.67-99.08%) and 98.71% (PI: 98.43-98.96%),
      respectively. After accounting for the imperfect sensitivity and specificity of
      the cELISA, the Bayesian posterior prevalence of FLUAV exposure among tested
      Italian dogs was 0.5% (PI: 0.1-1.4%). The study results indicate that screening
      with a cELISA for influenza A nucleoprotein antibody, followed by confirmatory
      testing with HI and/or FAT, is a highly sensitive and highly specific approach
      for diagnosing FLUAV exposure in dogs.

PMID- 21088177
TI  - A multiphasic typing approach to subtype Streptococcus equi subspecies equi.
AB  - The objective of the present investigation was to differentiate between strains
      of Streptococcus equi subspecies equi implicated in abscess formation in
      vaccinated horses. Streptococcus equi isolates recovered from clinical specimens
      associated with equine strangles cases submitted to the University of Illinois
      Veterinary Diagnostic Laboratory were compared with S. equi isolates representing
      at least 12 lots of a commercial modified live vaccine (MLV) to determine whether
      the isolates obtained from the abscesses were vaccine or wild type. Genotyping
      techniques evaluated included enterobacterial repetitive intergenic consensus
      polymerase chain reaction (PCR), repetitive extragenic palindrome PCR, BOX
      element PCR, ribotyping, and pulsed-field gel electrophoresis (PFGE). Phenotypic
      evaluations were performed using the Biolog GP2 Microplate (hereafter, Biolog).
      In cases where Biolog and PFGE results did not coincide, a single nucleotide
      polymorphism located in the upstream regulatory region of szp gene was used to
      identify the S. equi strains. PFGE and Biolog successfully differentiated wild
      type S. equi strains isolated from clinical submissions from isolates of the MLV.
      PFGE genotyping enabled further subtyping of the wild-type strains, whereas
      Biolog combined with szp sequencing was useful in differentiating the MLV strain
      from its wild-type progenitor. Deletion of a single guanine residue located in
      the upstream regulatory region of the szp gene appears to be conserved among
      vaccine isolates, and shows a 98.5% correlation to Biolog identification. This
      multiphasic approach can be used to answer specific diagnostic questions
      pertaining to the source of infection and/or outbreak, or to address quarantine
      concerns.

PMID- 21088176
TI  - Histologic and bacteriologic findings in valvular endocarditis of slaughter-age
      pigs.
AB  - Endocarditis lesions from 117 slaughter pigs were examined pathologically and
      etiologically in addition to 90 control hearts with cardiac valves. Lesions were
      located on the valves; however, the lesions had extended to the walls in 21 cases
      (18%). Lesions predominated on the mitral valve (59%). A total of 28 cases, from
      which no growth was obtained or a contamination flora was grown, were screened by
      fluorescence in situ hybridization (FISH) for bacteria (general bacterial probe)
      and probes specific for Streptococcus suis and Erysipelothrix rhusiopathiae,
      respectively. Using FISH, an additional 10 cases of endocarditis due to S. suis
      and E. rhusiopathiae were disclosed. Within lesions, streptococci predominated
      (53%) followed by E. rhusiopathiae (30%). Distinct features of both the lesions
      and the shape and localization of bacterial colonies were related to streptococci
      and E. rhusiopathiae. The propensity for streptococci to be localized on more
      than 1 valve in single hearts may be because S. suis-infected pigs tend to have
      been infected for a longer period compared with E. rhusiopathiae. Mineralization
      of endocarditis lesions was significantly associated with infection by
      streptococci, and was seen in 71% of the cases, whereas it was present in only
      28% of lesions caused by E. rhusiopathiae. In addition, areas with mineralization
      were significantly correlated to the presence of a granulomatous reaction.
      Granulomatous endocarditis is likely a result of a foreign body reaction due to
      dystrophic mineralization. Local proliferation of valvular endothelial cells,
      found in 9 hearts in the current study, may increase the risk of developing
      thrombosing endocarditis in pigs.

PMID- 21088178
TI  - Comparison of the fibers of Fowl adenovirus A serotype 1 isolates from chickens
      with gizzard erosions in Europe and apathogenic reference strains.
AB  - A total of 18 samples from 4 outbreaks of gizzard erosions in broiler chickens in
      Europe were used in the current study. Fowl adenoviruses were found in samples
      from all 4 outbreaks, and isolates were identified as Fowl adenovirus A (FAdV-A)
      serotype 1. As described earlier, polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) analysis of the long fiber gene was conducted.
      However, all 18 samples showed the same pattern as apathogenic FAdV-1 strains:
      Ote and chicken embryo lethal orphan (CELO) viruses. Nucleotide and amino acid
      sequences of the long and short fiber of several isolates from broiler chickens
      with gizzard erosions were analyzed, and 100% identity between the field isolates
      on the protein level was revealed. Only 1 nonsynonymous mutation (T->A) was
      present in the long fiber of studied isolates compared to the CELO strain. The
      same mutation was also present in the Ote strain. Four nonsynonymous mutations
      were present in the long fiber of studied isolates compared to Ote strain. In the
      short fiber, 6 nonsynonymous mutations were found in the studied isolates
      compared to the CELO strain. However, the short fiber of pathogenic isolates was
      100% identical to apathogenic Ote strain. In conclusion, the usefulness of PCR
      RFLP analysis of the long fiber gene of FAdV-1 isolates in distinguishing between
      those that induce gizzard erosions and those that do not remains questionable for
      the isolates obtained from European poultry flocks. The role of certain FAdV-1
      strains with their long and short fiber in pathogenicity regarding gizzard
      erosions is still not clear.

PMID- 21088179
TI  - Diagnostic application of H3N8-specific equine influenza real-time reverse
      transcription polymerase chain reaction assays for the detection of Canine
      influenza virus in clinical specimens.
AB  - The objective of the current study was to determine the capability of 3 recently
      described one-step TaqMan real-time reverse transcription polymerase chain
      reaction (real-time RT-PCR) assays targeting the nucleoprotein (NP), matrix (M),
      and hemagglutinin (HA) genes of H3N8 Equine influenza virus (EIV NP, EIV M, and
      EIV HA3 assays, respectively) to detect Canine influenza virus (CIV). The assays
      were initially evaluated with nucleic acid extracted from tissue culture fluid
      (TCF) containing the A/canine/FL/43/04 strain of Influenza A virus associated
      with the 2004 canine influenza outbreak in Florida. The EIV NP, EIV M, and EIV
      HA3 assays could detect CIV nucleic acid at threshold cycle (Ct) values of 16.31,
      23.71, and 15.28, respectively. Three assays using TCF or allantoic fluid (AF)
      samples containing CIV (n  =  13) and archived canine nasal swab samples (n  = 
      20) originally submitted for laboratory diagnosis of CIV were further evaluated.
      All TCF and AF samples, together with 10 nasal swab samples that previously
      tested positive for virus by attempted isolation in embryonated hens' eggs or
      Madin-Darby canine kidney cells, were positive in all 3 real-time RT-PCR assays.
      None of the 3 assays detected the H1N1 Swine influenza virus strain in current
      circulation. These findings demonstrate that previously described real-time RT
      PCR assays targeting NP, M, and H3 HA gene segments of H3N8 EIV are also valuable
      for the diagnosis of CIV infection in dogs. The assays could expedite the
      detection and identification of CIV.

PMID- 21088180
TI  - Consistent detection of Felis domesticus papillomavirus 2 DNA sequences within
      feline viral plaques.
AB  - Viral plaques are well recognized skin lesions of cats. They are thought to be
      caused by papillomavirus infection; however, the causative papillomavirus is
      uncertain. In the current study, polymerase chain reaction using 2 consensus
      primer sets and 1 primer set specific for Felis domesticus papillomavirus 2 (FdPV
      2) was used to amplify DNA from a series of 14 feline viral plaques. The FdPV-2
      sequences were detected in all 14 viral plaques by the specific primers but in
      only 1 of 14 feline cutaneous trichoblastomas. Papillomavirus DNA was amplified
      from 8 plaques using the consensus primers. Sequences from FdPV-2 were amplified
      using the consensus primers from 4 plaques. In addition, 3 plaques contained
      papillomavirus DNA sequences from Felis domesticus papillomavirus sequence MY1,
      and a previously unreported papillomavirus DNA sequence was amplified from 1
      plaque. As FdPV-2 was consistently present within the plaques, this suggests that
      this papillomavirus is the likely etiologic agent. Feline viral plaques can
      undergo neoplastic transformation to Bowenoid in situ carcinomas (BISCs). As FdPV
      2 DNA is frequently present within BISCs, this suggests that FdPV-2 induces viral
      plaque formation and then remains detectible after neoplastic transformation.

PMID- 21088181
TI  - The 51-chromium-labeled ethylenediamine tetra-acetic acid intestinal permeability
      blood test in healthy Beagle dogs: a comparison between serum and plasma levels.
AB  - A 51-chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA)
      permeability blood test was validated as a method to assess damage to the small
      intestine in dogs. The test was performed by calculating various percentages from
      sera after an orally ingested dose solution. The aim of the current study was to
      determine whether the use of serum or plasma had any influence on the results of
      the test. A test solution with 3.7 megabecquerel (100 uCi) of (51)Cr-EDTA was
      delivered through an orogastric tube to 13 healthy laboratory Beagle dogs. From
      each dog, 2 concurrent blood samples were withdrawn from cephalic veins using
      clotting-factor activator tubes for serum and heparinized tubes for plasma. The
      samples (n  =  26) were taken at 3 and 5 hr after administration of the test
      solution. Percentages of the orally ingested dose were then calculated in serum
      and plasma, and their relationship was assessed using correlation analysis. The
      mean +/- standard deviation percentages in serum and plasma after 3 hr were 0.85
      +/- 0.43% and 0.88 +/- 0.49%, respectively, whereas respective percentages in
      serum and plasma after 5 hr were 0.78 +/- 0.52% and 0.81 +/- 0.51%. The combined
      correlation coefficient between the percentages from the sera and plasma samples
      was excellent (R  =  0.98). It was concluded that the (51)Cr-EDTA permeability
      test in blood may be performed using serum or plasma of dogs, and the choice
      between the 2 samples is one of convenience.

PMID- 21088182
TI  - Retrospective study of necropsy-associated coagulase-positive staphylococci in
      horses.
AB  - Coagulase-positive staphylococci (CoPS) are potential causative agents of equine
      infections, but they are rarely responsible for the death of the animal. In the
      current study, staphylococci implicated in the death or euthanasia of horses were
      retrospectively studied in 3,457 necropsies performed over a decade (1995-2006).
      Morbidity associated with CoPS was 1.7%, representing 60 isolates of CoPS, which
      were identified as Staphylococcus aureus (59) and Staphylococcus pseudintermedius
      (1). Coagulase-positive staphylococci (alone or in association with another
      bacterial species) were associated with the death or euthanasia of 90% of the
      cases (54/60). Proportions of antibiotic resistance to penicillin G and
      tetracycline reached 62.7% and 23.7%, respectively. Virulence genes were detected
      in 91.7% of the strains, with a majority of seh or sei enterotoxin genes.
      Finally, 3 methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging
      to the t064 spa-type were identified. One strain was isolated in 2003 and might
      thus be one of the first cases of equine MRSA in France.

PMID- 21088183
TI  - Mycoplasma bovis real-time polymerase chain reaction assay validation and
      diagnostic performance.
AB  - Mycoplasma bovis is an important bacterial pathogen in cattle, producing a
      variety of clinical diseases. The organism, which requires specialized culture
      conditions and extended incubation times to isolate and identify, is frequently
      associated with concurrent infection with other pathogens which can potentially
      be more easily identified. Real-time polymerase chain reaction (real-time PCR) is
      a valuable diagnostic technique that can rapidly identify infectious agents in
      clinical specimens. A real-time PCR assay was designed based on the uvrC gene to
      identify M. bovis in diagnostic samples. Using culture as the gold standard test,
      the assay performed well in a variety of diagnostic matrices. Initial validation
      testing was conducted on 122 milk samples (sensitivity: 88.9% [95% confidence
      interval (CI): 68.4-100%], specificity: 100%); 154 lung tissues (sensitivity:
      89.0% [95% CI: 83.1-94.9%], specificity: 97.8% [95% CI: 93.5-100%]); 70 joint
      tissue/fluid specimens (sensitivity: 92.3% [95% CI: 82.1-100%], specificity:
      95.5% [95% CI: 89.3-100%]); and 26 nasal swabs (sensitivity: 75.0% [95% CI: 45.0
      100%], specificity: 83.3% [95% CI: 66.1-100%]). Low numbers of other sample
      matrices showed good agreement between results of culture and PCR. A review of
      clinical cases from 2009 revealed that, in general, PCR was used much more
      frequently than culture and provided useful diagnostic information in conjunction
      with clinical signs, signalment, and gross and histopathologic lesions.
      Diagnostic performance of the real-time PCR assay developed as a testing method
      indicates that it is a rapid, accurate assay that is adaptable to a variety of
      PCR platforms and can provide reliable results on an array of clinical samples.

PMID- 21088184
TI  - Proventricular dilatation disease associated with Avian bornavirus in a scarlet
      macaw (Ara macao).
AB  - A case of proventricular dilatation disease is described in a scarlet macaw (Ara
      macao) from clinical presentation to diagnosis with molecular methods. The
      initial clinical signs were depression progressing to head pressing over several
      days. A leukocytosis with toxic heterophil changes, hypoalbuminemia, and
      increased serum activity of aspartate aminotransferase and creatine kinase were
      present. Lead and zinc assays were within reference ranges, and results from
      Chlamydophila and polyomavirus testing were negative. Contrast-enhanced
      fluoroscopy revealed normal gastrointestinal transit times and motility as well
      as the presence of 2 small metallic foreign bodies in the ventriculus. The macaw
      was treated with antimicrobials, analgesics, vitamins E and B complex, force
      feeding, and fluid administration with little improvement. Euthanasia was
      elected, and histologic examination of brain tissue revealed a perivascular
      lymphoplasmacytic infiltration, while the lungs had evidence of a fungal
      pneumonia. Tissue samples from the brain and proventriculus tested positive for
      the presence of Avian bornavirus genotype 2, while serology confirmed Avian
      bornavirus infection.

PMID- 21088185
TI  - Chronic myositis in an Australian alpaca (Llama pacos) associated with
      Sarcocystis spp.
AB  - An alpaca (Llama pacos), born and raised in Australia, was presented with
      multiple subcutaneous abscesses. Histological findings indicated a severe
      necrotizing and histiocytic myositis and cellulitis associated with central
      caseation and multiple sarcocysts. Ultrastructural examination supported the
      diagnosis; however, cyst wall characteristics were not consistent with the 2
      known species found in alpacas. While seroconversion in camelids is reported to
      be near ubiquitous, myositis is rare, and this is the first case reported outside
      of the Americas.

PMID- 21088186
TI  - Clinical course of a malignant peripheral nerve sheath tumor in a Siberian tiger
      (Panthera tigris altaica).
AB  - A 14-year-old male Siberian tiger (Panthera tigris altaica) was admitted with an
      ulcerating mass on the right thoracic wall. Radiographic and computed tomographic
      evaluation indicated 2 isolated cutaneous masses without any signs of metastasis.
      Histology of a Tru-Cut biopsy revealed an anaplastic sarcoma with giant cells.
      Both tumors were resected with appropriate normal tissue margins. The size of the
      defect did not allow primary closure of the wound; therefore, a mesh expansion
      technique was attempted. Three months later, the tiger had to be euthanized due
      to extensive metastasis to the lungs. Histomorphological features and
      immunohistochemical results confirmed the diagnosis of malignant peripheral nerve
      sheath tumor. In contrast to domestic animal experience, the tumor had spread
      extensively to the lungs without local reccurrence in a short period of time.
      Correct diagnosis requires various immunohistochemical evaluations of the tumor
      tissue.

PMID- 21088187
TI  - Necrotizing sialometaplasia of the parotid gland in a dog.
AB  - Necrotizing sialometaplasia (NS) is a self-limiting, benign, ischemic,
      inflammatory disease that is most often described in the submandibular glands of
      dogs, with clinical and histologic features that resemble malignancy. Unilateral
      swelling of the parotid salivary gland in a 7-year-old Cocker Spaniel dog was
      diagnosed as NS. The dog also had otitis externa on the same side as the parotid
      gland lesions. The main histologic features were included lobular necrosis of
      salivary tissue; fibrinoid necrosis of some arteries; marked squamous metaplasia
      of duct and/or acinar epithelium, with intercellular bridge formation;
      preservation of salivary lobular morphology; and variable inflammation and
      fibrosis. Etiologic factors for NS in both humans and animals remain obscure.

PMID- 21088188
TI  - Desmoplastic ganglioglioma of the spinal cord in a western European hedgehog
      (Erinaceus europaeus).
AB  - Gangliogliomas are composed of neoplastic glial and neuronal cells and are
      extremely rare tumors of the central nervous system of domestic animals. The
      present report describes the clinical presentation and the pathomorphological and
      immunophenotypical characteristics of a desmoplastic ganglioglioma in the spinal
      cord of a 3-year-old male western European hedgehog (Erinaceus europaeus).
      Clinically, the hedgehog exhibited a skin wound and therapy-resistant paresis of
      the left hind limb. Necropsy showed dilatation of the urinary bladder. Histologic
      examination of the thoracic spinal cord revealed a focally extensive infiltrative
      mass, which consisted of multiple nodules of smaller bipolar or oligopolar glial
      cells and variably sized polygonal, ganglionic, neuron-like cells embedded in
      variable amounts of microcystic neuropilic matrix. An area of spindle-shaped
      cells arranged in interwoven fascicles and surrounded by a prominent network of
      reticulin fibers was interpreted as desmoplastic leptomeningeal stroma.
      Immunohistochemistry revealed a moderate number of glial fibrillary acidic
      protein and S-100-positive cells and processes. In addition, the ganglionic
      neuron-like cells expressed neurofilament, microtubule-associated protein-2, and
      neuron-specific enolase. In summary, this spinal cord tumor was composed of
      astroglial and neuronal cellular elements, justifying the diagnosis of a
      desmoplastic ganglioglioma.

PMID- 21088189
TI  - Chromophobe renal cell carcinoma with sarcomatoid transformation in a dog.
AB  - A 12-year-old spayed female Siberian husky dog presented with hematuria and
      weight loss. An abdominal ultrasonographic examination revealed a left renal
      tumor measuring 8 cm in diameter, and a nephrectomy was performed. The resected
      kidney contained a cavitated tumor with a white solid region. Histologically,
      this tumor was composed of large polygonal cells with abundant and cloudy
      cytoplasm and focal sarcomatoid change. The neoplastic epithelial cells were
      reactive with colloidal iron staining; Dolichos biflorus agglutinin, peanut
      agglutinin, and Ulex europaeus agglutinin I lectins; and cluster of
      differentiation 10 and c-KIT antigens but not for periodic acid-Schiff or
      vimentin stain. Neoplastic sarcomatoid cells stained positive for vimentin.
      Because these histopathologic features are identical to those of human
      chromophobe renal cell carcinoma, the present case was diagnosed as canine
      chromophobe renal cell carcinoma.

PMID- 21088190
TI  - Ameloblastic fibro-odontoma associated with a retained molar in an Oldenburg
      mare.
AB  - An 11-year-old Oldenburg mare presented with a 3-month history of weight loss and
      swelling of the posterior right mandible. Physical examination and radiographs
      showed a soft-tissue mass in the right mandible with foci of mineralization,
      periosteal proliferation, and a retained molar. The tumor increased in size over
      several weeks, and the mare was euthanized. On necropsy, a 24 cm * 15 cm * 15 cm
      firm, white mass had obliterated the posterior right mandible. The mass was
      multinodular with discrete clusters of blood-filled cystic spaces.
      Histologically, the mass was composed of neoplastic odontogenic epithelium and
      pulpal mesenchyme with an accumulation of eosinophilic material resembling dentin
      or enamel. Microscopic and immunohistochemical staining features of the neoplasm
      were most consistent with an ameloblastic fibro-odontoma.

PMID- 21088191
TI  - Spontaneous pneumothorax in a dog secondary to Dirofilaria immitis infection.
AB  - A 5-year-old female spayed Labrador Retriever dog was referred to the Louisiana
      State University Veterinary Teaching Hospital for treatment of pneumothorax.
      Thoracic radiographs and computed tomography showed spontaneous pneumothorax,
      thoracic lymphadenopathy, pulmonary hypertension, and multifocal pulmonary bulla
      lesions. At surgery, numerous adult nematodes protruded from the parenchyma of
      the left caudal and accessory lung lobes and pulmonary arteries. On
      histopathology, multiple adult filarid nematodes were observed within the
      pulmonary blood vessels. Broad foci of necrosis of the pulmonary parenchyma were
      present. The tunica intima of the pulmonary arteries was markedly thickened by
      intimal fibrosis and medial hypertrophy. The final diagnosis was severe
      Dirofilaria immitis infection that resulted in pulmonary vascular lesions and
      focally extensive infarcts of the pulmonary parenchyma with bulla formation and
      rupture causing spontaneous pneumothorax. The dog received antibiotic and steroid
      therapy, as well as adulticide treatment, and recovered.

PMID- 21088193
TI  - Spontaneous odontoameloblastoma in a female Sprague Dawley rat.
AB  - The present report describes a spontaneously developing, highly infiltrative, and
      expansile neoplasm in the mandible of a 9-month-old female Sprague Dawley rat.
      The lesion consisted of abundant odontogenic epithelium with induction of
      osteodentin in the adjacent mesenchyme and was classified therefore as an
      odontoameloblastoma. Odontoameloblastomas are reported uncommonly in domestic
      animals, and the histologic and histochemical features of this neoplasm are
      reported herein along with a review of the veterinary literature.

PMID- 21088192
TI  - Bovine subclinical mastitis caused by Mannheimia granulomatis.
AB  - Mannheimia granulomatis was isolated for 10 months from the milk of a cow with
      elevated somatic cell counts. The infection was self-limiting. Phenotypic and
      molecular characteristics of the isolate were determined.

PMID- 21088194
TI  - Lycoperdonosis in two dogs.
AB  - Lycoperdonosis is a rare respiratory disease that results from the inhalation of
      spores released from the Lycoperdon (puffball) mushroom. In the present study, 2
      cases of confirmed canine lycoperdonosis are described. The first case presented
      to the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania, and
      the second case was submitted for postmortem examination to the University of
      Tennessee Veterinary Teaching Hospital. Both dogs presented in respiratory
      distress, and owners reported that the dogs had been playing or digging in areas
      with puffball mushrooms prior to the onset of clinical signs. In the initial
      case, thoracic radiographs revealed a diffuse interstitial and multifocal
      alveolar pulmonary pattern. Despite aggressive medical treatment and mechanical
      ventilation, the dog continued to worsen and was euthanized. Postmortem
      examination revealed firm lung lobes and enlarged tracheobronchial lymph nodes.
      Histologically, there was a severe diffuse histiocytic and pyogranulomatous
      bronchointerstitial pneumonia. Throughout the lung and lymph nodes, most commonly
      within macrophages, were round, 3-5 um in diameter, Gomori methenamine silver
      positive structures, consistent with Lycoperdon spores. An approximately 750-base
      pair DNA fragment was amplified from lung of both cases by polymerase chain
      reaction using primers specific to yeast ribosomal DNA, and the sequence of the
      fragment was determined to be most closely related to Lycoperdon pyriforme.
      Importantly, reexamination of an endotracheal wash from the initial case revealed
      intrahistiocytic spores, suggesting that airway sampling may assist in diagnosing
      lycoperdonosis.

PMID- 21088195
TI  - Mammary carcinoma in a ewe.
AB  - Mammary tumors of all types are rare in herbivores, and there is a particular
      paucity of reports in sheep. The present report describes a case of mammary
      carcinoma in a 6-year-old uniparous ewe. The tumor was present for at least 18
      months, during which time the ewe remained clinically well. At postmortem
      examination, the mass was found to be multilobulated with occasional cysts.
      Histologically, the lobules consisted of tubules lined by cuboidal to low
      columnar epithelium with loss of polarity and moderate anisokaryosis within a
      moderately extensive fibrous stroma. It was classified as a low-grade carcinoma.
      The histologic classification and lack of evidence of invasion correlated well
      with the slow clinical progression.

PMID- 21088196
TI  - Retroperitoneal pulmonary choristoma in a newborn calf.
AB  - A newborn male Romagnola calf, who had died a few hours after birth, was
      submitted for postmortem examination. Necropsy revealed a 23 cm * 22 cm * 5 cm,
      pale pink, lobulated, elastic, partially fluctuant mass that protruded from the
      dorsal retroperitoneal space into the abdominal cavity, extending from the
      diaphragm to the left kidney. The mass consisted of mature pulmonary tissue and
      was consistent with a pulmonary choristoma. The gross and microscopic appearance
      of this rare tumor-like congenital lesion and the possible pathogenesis are
      discussed.

PMID- 21088197
TI  - Intrapericardial ectopic thyroid carcinoma in a cat.
AB  - A 7-year-old spayed female domestic shorthair feline presented with tachycardia
      and was later euthanized due to a declining condition. On gross examination, the
      thoracic cavity contained an expansile, multiloculated mass that displaced the
      lungs dorsocaudally. The mass, within the pericardial sac, compressed adjacent
      myocardium. Cut surface revealed variably sized, fluid-filled spaces with
      multiple foci of hemorrhage and necrosis. Histologically, the mass was composed
      of solid foci of polygonal cells admixed with colloid-containing follicles.
      Immunohistochemical staining for thyroglobulin was positive, and staining for
      calcitonin was negative. Grossly, thyroid glands were normal, and serum thyroxine
      was within reference intervals.

PMID- 21088198
TI  - Endocardial fibrosarcoma in a reticulated python (Python reticularis).
AB  - A female, reticulated python (Python reticularis) of unknown age was presented
      with a history of lethargy, weakness, and distended coelom. Physical examination
      revealed severe dystocia and stomatitis. The reticulated python was euthanized
      due to a poor clinical prognosis. Postmortem examination revealed marked
      distention of the reproductive tract with 26 eggs (10-12 cm in diameter),
      pericardial effusion, and a slightly firm, pale tan mass (3-4 cm in diameter)
      adhered to the endocardium at the base of aorta. Based on histopathologic and
      transmission electron microscopic findings, the diagnosis of endocardial
      fibrosarcoma was made.

PMID- 21088201
TI  - In patients undergoing mitral surgery for ischaemic mitral regurgitation is it
      preferable to repair or replace the mitral valve?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether patients undergoing coronary bypass grafting and
      mitral intervention for moderate to severe ischaemic mitral regurgitation are
      best treated with mitral repair or replacement. Five hundred and fifty papers
      were found using the reported search. Based on the 14 non-randomised studies
      judged to represent best evidence, we concluded that whilst there is some
      evidence that the operative mortality may be less following mitral valve repair,
      long-term data are equivocal. Even with contemporary techniques, recurrent mitral
      regurgitation is not uncommon following repair. Replacement was more frequently
      performed for patients with greater co-morbidity. Whilst two studies attempted to
      control for this using propensity analysis, in the majority of studies this
      introduced considerable bias. No data was available on long-term functional
      outcomes and quality of life. As there is currently insufficient evidence to
      inform clinical practice, a randomised trial is warranted in this important area.

PMID- 21088200
TI  - Hepatocyte nuclear factor 4alpha regulates expression of the mouse female
      specific Cyp3a41 gene in the liver.
AB  - CYP3A41 is a female-specific cytochrome P450 in mouse liver. A putative
      hepatocyte nuclear factor 4alpha (HNF4alpha)-binding site was found at -99/-87 in
      the promoter of Cyp3a41 by reporter assays performed in the hepatocytes of female
      mice. Cotransfection of an HNF4alpha expression plasmid significantly increased
      transcription of the reporter gene. Although electrophoretic mobility shift
      assays with liver nuclear extracts did not show a sex-related difference,
      chromatin immunoprecipitation (ChIP) assays showed that larger amounts of
      HNF4alpha bound to Cyp3a41 in female than in male mice. A relation between the
      amount of HNF4alpha on the Cyp3a41 gene and mRNA expression was observed in
      hepatic tissue sets, which differ in mRNA expression depending on the sex, age,
      or endocrine status of mice. The degree of histone-3-lysine-4 dimethylation and
      histone-3-lysine-27 trimethylation around the HNF4alpha-binding site was higher
      in females and males, respectively. Moreover, the ChIP assay indicated greater
      acetylation of histone-4-lysine-8 of the Cyp3a41 chromatin in females than in
      males. HNF4alpha plays an important role in the transcriptional activation of the
      Cyp3a41 gene, and a sex difference in chromatin structure may contribute to the
      female-specific expression of Cyp3a41 in the livers of mice.

PMID- 21088202
TI  - Effect of acute high-intensity interval exercise on postexercise biventricular
      function in mild heart failure.
AB  - We studied the acute effect of high-intensity interval exercise on biventricular
      function using cardiac magnetic resonance imaging in nine patients [age: 49 +/-
      16 yr; left ventricular (LV) ejection fraction (EF): 35.8 +/- 7.2%] with
      nonischemic mild heart failure (HF). We hypothesized that a significant
      impairment in the immediate postexercise end-systolic volume (ESV) and end
      diastolic volume (EDV) would contribute to a reduction in EF. We found that
      immediately following acute high-intensity interval exercise, LV ESV decreased by
      6% and LV systolic annular velocity increased by 21% (both P < 0.05). Thirty
      minutes following exercise (+30 min), there was an absolute increase in LV EF of
      2.4% (P < 0.05). Measures of preload, left atrial volume and LV EDV, were reduced
      immediately following exercise. Similar responses were observed for right
      ventricular volumes. Early filling velocity, filling rate, and diastolic annular
      velocity remained unchanged, while LV untwisting rate increased 24% immediately
      following exercise (P < 0.05) and remained 18% above baseline at +30 min (P <
      0.05). The major novel findings of this investigation are 1) that acute high
      intensity interval exercise decreases the immediate postexercise LV ESV and
      increases LV EF at +30 min in patients with mild HF, and this is associated with
      a reduction in LV afterload and maintenance of contractility, and 2) that despite
      a reduction in left atrial volume and LV EDV immediately postexercise, diastolic
      function is preserved and may be modulated by enhanced LV peak untwisting rate.
      Acute high-intensity interval exercise does not impair postexercise biventricular
      function in patients with nonischemic mild HF.

PMID- 21088203
TI  - Increased brachial artery retrograde shear rate at exercise onset is abolished
      during prolonged cycling: role of thermoregulatory vasodilation.
AB  - Acute leg exercise increases brachial artery retrograde shear rate (SR), while
      chronic exercise improves vasomotor function. These combined observations are
      perplexing given the proatherogenic impacts of retrograde shear stress on the
      vascular endothelium and may be the result of brief protocols used to study acute
      exercise responses. Therefore, we hypothesized that brachial artery retrograde SR
      increases initially but subsequently decreases in magnitude during prolonged leg
      cycling. Additionally, we tested the role of cutaneous vasodilation in the
      elimination of increased retrograde SR during prolonged exercise. Brachial artery
      diameter and velocity profiles and forearm skin blood flow and temperature were
      measured at rest and during 50 min of steady-state, semirecumbent leg cycling
      (120 W) in 14 males. Exercise decreased forearm vascular conductance (FVC) and
      increased retrograde SR at 5 min (both P < 0.05), but subsequently forearm and
      cutaneous vascular conductance (CVC) rose while retrograde SR returned toward
      baseline values. The elimination of increased retrograde SR was related to the
      increase in FVC (r(2) = 0.58; P < 0.05) and CVC (r(2) = 0.32; P < 0.05).
      Moreover, when the forearm was cooled via a water-perfused suit between minutes
      30 and 40 to blunt cutaneous vasodilation attending exercise, FVC was reduced and
      the magnitude of retrograde SR was increased from -49.7 +/- 13.6 to -78.4 +/-
      16.5 s(-1) (P < 0.05). Importantly, these responses resolved with removal of
      cooling during the final 10 min of exercise (retrograde SR: -46.9 +/- 12.5 s(
      1)). We conclude that increased brachial artery retrograde SR at the onset of leg
      cycling subsequently returns toward baseline values due in part to
      thermoregulatory cutaneous vasodilation during prolonged exercise.

PMID- 21088204
TI  - Understanding the regulation of muscle plasticity.

PMID- 21088205
TI  - Enhanced technique to measure proteins in single segments of human skeletal
      muscle fibers: fiber-type dependence of AMPK-alpha1 and -beta1.
AB  - Human physiological studies typically use skeletal muscle biopsies from the
      heterogeneous vastus lateralis muscle comprised of both fast-twitch and slow
      twitch fiber types. It is likely that potential changes of physiological
      importance are overlooked because fiber-type specific responses may not be
      apparent in the whole muscle preparation. A technological advance in Western
      blotting is presented where proteins are analyzed in just one small segment (<2
      mm) of individual fibers dissected from freeze-dried muscle samples using
      standard laboratory equipment. A significant advance is being able to classify
      every fiber at the level of both contractile (myosin heavy chain and tropomyosin)
      and sarcoplasmic reticulum [sarco(endo)plasmic reticulum Ca(2+)-ATPase type 1]
      properties and then being able to measure specific proteins in the very same
      segments. This removes the need to fiber type segments before further analyses
      and, as such, dramatically reduces the time required for sample collection.
      Compared with slow-twitch fibers, there was less AMP-activated protein kinase
      (AMPK)-alpha(1) (~25%) and AMPK-beta(1) (~60%) in fast-twitch fibers from human
      skeletal muscle biopsies.

PMID- 21088206
TI  - Influence of training and maturity status on the cardiopulmonary responses to
      ramp incremental cycle and upper body exercise in girls.
AB  - It has been suggested that the potential for training to alter the physiological
      responses to exercise in children is related to a "maturational threshold". To
      address this, we investigated the interaction of swim-training status and
      maturity on cardiovascular and metabolic responses to lower and upper body
      exercise. Twenty-one prepubertal [Pre: 11 trained (T), 10 untrained (UT)], 30
      pubertal (Pub: 14 T, 16 UT), and 18 postpubertal (Post: 8 T, 10 UT) girls
      completed ramp incremental exercise on a cycle and an upper body ergometer. In
      addition to pulmonary gas exchange measurements, stroke volume and cardiac output
      were estimated by thoracic bioelectrical impedance, and muscle oxygenation status
      was assessed using near-infrared spectroscopy. All T girls had a higher peak O(2)
      uptake during cycle (Pre: T 49 +/- 5 vs. UT 40 +/- 4; Pub: T 46 +/- 5 vs. UT 36
      +/- 4; Post: T 48 +/- 5 vs. UT 39 +/- 8 ml.kg(-1).min(-1); all P < 0.05) and
      upper body exercise (Pre: T 37 +/- 6 vs. UT 32 +/- 5; Pub: T 36 +/- 5 vs. UT 28
      +/- 5; Post: T 39 +/- 3 vs. UT 28 +/- 7 ml.kg(-1).min(-1); all P < 0.05). T girls
      also had a higher peak cardiac output during both modalities, and this reached
      significance in Pub (cycle: T 21 +/- 3 vs. UT 18 +/- 3; upper body: T 20 +/- 4
      vs. UT 15 +/- 4 l/min; all P < 0.05) and Post girls (cycle: T 21 +/- 4 vs. UT 17
      +/- 2; upper body: T 22 +/- 3 vs. UT 18 +/- 2 l/min; all P < 0.05). None of the
      measured pulmonary, cardiovascular, or metabolic parameters interacted with
      maturity, and the magnitude of the difference between T and UT girls was similar,
      irrespective of maturity stage. These results challenge the notion that
      differences in training status in young people are only evident once a
      maturational threshold has been exceeded.

PMID- 21088207
TI  - Absence of cross-limb transfer of performance gains following ballistic motor
      practice in older adults.
AB  - The phenomenon of cross-limb transfer, in which unilateral strength training can
      result in bilateral strength gains, has recently been tested for ballistic
      movements. Performance gains associated with repetitive motor practice, and the
      associated transfer, occur within a few minutes. In this study, young and older
      adults were trained to perform ballistic abductions of their dominant (right)
      index finger as quickly as possible. Performance was assessed bilaterally before,
      during, and after this training. Both groups exhibited large performance gains in
      the right hand as a result of training (P < 0.001; young 84% improvement, older
      70% improvement), which were not significantly different between groups (P =
      0.40). Transcranial magnetic stimulation revealed that the performance
      improvements were accompanied by increases in excitability, together with
      decreases in intracortical inhibition, of the projections to both the trained
      muscle and the homologous muscle in the contralateral limb (P < 0.05). The young
      group also exhibited performance improvements as a result of cross-limb transfer
      in the left (untrained) hand (P < 0.005), equivalent to 75% of the performance
      increase in the trained hand. In contrast, there were no significant performance
      gains in the left hand for the older group (P = 0.23). This was surprising given
      that the older group exhibited a significantly greater degree of mirror activity
      than the young group (P < 0.01) in the left first dorsal interosseus muscle (FDI)
      during right hand movements. Our findings suggest that older adults exhibit a
      reduced capacity for cross-limb transfer, which may have implications for motor
      rehabilitation programs after stroke.

PMID- 21088208
TI  - Reduced hyperthermia-induced cutaneous vasodilation and enhanced exercise-induced
      plasma water loss at simulated high altitude (3,200 m) in humans.
AB  - We examined whether less convective heat loss during exercise at high altitude
      than at sea level was partially caused by reduced cutaneous vasodilation due to
      enhanced plasma water loss into contracting muscles and whether it was caused by
      hypoxia rather than by hypobaria. Seven young men performed cycling exercise for
      40 min at 50% peak aerobic power in normoxia at (710 mmHg) 610 m, determined
      before the experiments, in three trials: 1) normobaric normoxia at 610 m (CNT),
      2) hypobaric hypoxia [low pressure and low oxygen (LPLO)] at 3,200 m (510 mmHg),
      3) normobaric hypoxia [normal pressure and low oxygen (NPLO)] at 610 m, in an
      artificial climate chamber where atmospheric temperature and relative humidity
      were maintained at 30 degrees C and 50%, respectively. Subjects in CNT and LPLO
      breathed room air, whereas those in NPLO breathed a mixed gas of 14% O2 balanced
      N2, equivalent to the gas composition in LPLO. We measured change in PV
      (DeltaPV), oxygen consumption rate (Vo2), mean arterial blood pressure (MBP),
      esophageal temperature (T(es)), mean skin temperature (T(sk)), forearm skin blood
      flow (FBF), and sweat rate (SR) during exercise. Although Vo2, MBP, T(sk), and SR
      responses during exercise were similar between trials (P > 0.05), the sensitivity
      of forearm vascular conductance (FBF/MBP) in response to increased T(es) was
      lower in LPLO and NPLO than in CNT (P < 0.05), whereas that of SR was not,
      resulting in a greater increase in T(es) from minute 5 to 40 of exercise in LPLO
      and NPLO than in CNT (P = 0.026 and P = 0.011, respectively). DeltaPV during
      exercise was twofold greater in LPLO and NPLO than in CNT. These variables were
      not significantly different between LPLO and NPLO. Thus reduced convective heat
      loss during exercise at 3,200 m was partially caused by reduced cutaneous
      vasodilation due to enhanced PV loss. Moreover, this may be caused by hypoxia
      rather than by hypobaria.

PMID- 21088209
TI  - Effects of acute Rho kinase inhibition on chronic hypoxia-induced changes in
      proximal and distal pulmonary arterial structure and function.
AB  - Hypoxic pulmonary hypertension (HPH) is initially a disease of the small
      pulmonary arteries. Its severity is usually quantified by pulmonary vascular
      resistance (PVR). Acute Rho kinase inhibition has been found to reduce PVR toward
      control values in animal models, suggesting that persistent pulmonary
      vasoconstriction is the dominant mechanism for increased PVR. However, HPH may
      also cause proximal arterial changes, which are relevant to right ventricular
      (RV) afterload. RV afterload can be quantified by pulmonary vascular impedance,
      which is obtained via spectral analysis of pulsatile pressure-flow relationships.
      To determine the effects of HPH independent of persistent pulmonary
      vasoconstriction in proximal and distal arteries, we quantified pulsatile
      pressure-flow relationships before and after acute Rho kinase inhibition and
      measured pulmonary arterial structure with microcomputed tomography. In control
      lungs, Rho kinase inhibition decreased 0 Hz impedance (Z0), which is equivalent
      to PVR, from 2.1 +/- 0.4 to 1.5 +/- 0.2 mmHg.min.ml-1 (P < 0.05) and tended to
      increase characteristic impedance (Z(C)) from 0.21 +/- 0.01 to 0.22 +/- 0.01
      mmHg.min.ml-1. In HPH lungs, Rho kinase inhibition decreased Z0 (P < 0.05)
      without affecting Z(C). Microcomputed tomography measurements performed on lungs
      after acute Rho kinase inhibition demonstrated that HPH significantly decreased
      the unstressed diameter of the main pulmonary artery (760 +/- 60 vs. 650 +/- 80
      MUm; P < 0.05), decreased right pulmonary artery compliance, and reduced the
      frequency of arteries of diameter 50-100 MUm (both P < 0.05). These results
      demonstrate that acute Rho kinase inhibition reverses many but not all HPH
      induced changes in distal pulmonary arteries but does not affect HPH-induced
      changes in the conduit arteries that impact RV afterload.

PMID- 21088210
TI  - Diet-induced impaired glucose tolerance and gestational diabetes in the dog.
AB  - Glucose metabolism was compared in dogs consuming a chow/meat diet throughout
      pregnancy (P group, n = 6) and dogs switched to a high-fat/high-fructose (HFF)
      diet during the 4th-5th gestational week (gestation ?9 wk; P-HFF group; n = 6).
      An oral glucose tolerance test (OGTT; 0.9 g/kg) was administered in the 6th-7th
      gestational week, and a hyperinsulinemic [0-120 min: 1.8 pmol.kg(-1).min(-1) (low
      insulin); 120-240 min: 9 pmol.kg(-1).min(-1) (high insulin)] euglycemic clamp was
      performed the following week. Nonpregnant (NP) female dogs underwent OGTTs but
      not clamp studies. All P-HFF dogs exhibited impaired glucose tolerance (IGT) or
      gestational diabetes (GDM), but only one P dog had IGT. Insulin concentrations in
      P and P-HFF dogs were significantly lower than in NP dogs 30 and 60 min after the
      OGTT. Therefore, mean islet size and area were evaluated in P and NP dogs. These
      values did not differ between groups, and proliferating endocrine cells were rare
      in pregnancy. During exposure to high insulin, glucose infusion rate and hindlimb
      glucose uptake were ~30% greater (P < 0.05) and net hepatic glucose output was
      more suppressed (-5.5 +/- 6.1 vs. 7.8 +/- 2.8 mg.100 g liver(-1).min(-1), P <
      0.05) in P than in P-HFF dogs. In conclusion, in the 2nd trimester the canine
      pancreas does not exhibit islet hypertrophy, hyperplasia, or neogenesis. Combined
      with the lack of pancreatic adaptation, a HFF diet during late pregnancy produces
      a canine model of IGT and GDM without hyperinsulinemia but exhibiting liver and
      muscle insulin resistance.

PMID- 21088211
TI  - High dietary salt intake increases carotid blood pressure and wave reflection in
      normotensive healthy young men.
AB  - Dietary salt intake is associated with high brachial blood pressure (BP) and
      increased risk of cardiovascular disease. We investigated whether changes in
      dietary salt intake are associated with changes in central BP and wave reflection
      in healthy volunteers. Ten healthy normotensive male volunteers (22-40 yr)
      participated in a 6-wk double-blind randomized crossover study to compare a low
      dietary salt intake (60-80 mmol sodium/day) with a high-salt intake (low salt
      intake supplemented with 128 mmol sodium/day) on central BP and wave reflection.
      Brachial and carotid BP, carotid blood flow velocity, forward (P(f)) and backward
      (P(b)) pressure, wave intensity, body weight, and urinary electrolyte excretion
      were measured at the end of each crossover period. High salt intake significantly
      increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and
      increased wave reflection [ratio of backward to forward pressure (P(b)/P(f)) 0.13
      (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP
      [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body
      weight were also increased following high salt intake. High salt intake
      disproportionately increases central BP compared with brachial BP as a result of
      enhanced wave reflection. These effects may contribute to the adverse effect of
      high dietary salt intake on the risk of cardiovascular disease.

PMID- 21088212
TI  - Effects of acute cold exposure on carotid and femoral wave intensity indexes:
      evidence for reflection coefficient as a measure of distal vascular resistance.
AB  - Our aim was to investigate the effects of acute cold pressor test (CPT) on
      augmentation index (AI) and wave intensity (WI) indexes from right common carotid
      artery (RCCA) and right common femoral artery (RCFA) and to test whether the
      reflection coefficient (RC) from wave intensity analysis can reflect the distal
      vascular resistance (DVR) accurately. Forty-three healthy males were randomly
      selected for measurements at baseline and 1 min after CPT at RCCA or RCFA. CPT
      induced similar increases of heart rate and blood pressure in RCCA and RCFA
      groups with their pulse pressures unchanged. The W(2) (the second peak of WI) was
      too obscure in RCFA to be analyzed. The W(1) (the first peak of WI) of both
      arteries, W(1)-W(2) (interval between W(1) and W(2)), and NA (negative area
      between W(1) and W(2), indicating reflected waves) of RCCA and the R-W(1)
      (interval between the R wave of ECG and W(1)) of RCFA decreased obviously,
      whereas the W(2) and R-W(1) of RCCA and the RC (calculated as NA/W(1)) of RCFA
      increased with no changes in the RC of RCCA and the NA of RCFA during CPT
      compared with baseline. The AIs from both arteries increased significantly after
      CPT. These results suggested that acute CPT has opposing effects on cerebral and
      peripheral vascular resistances, with the former decreased and the latter
      increased. The RCs from RCCA and RCFA are more associated with the changes of
      cerebral and peripheral vascular resistances, respectively, than the NA and AI,
      and the RC is of guiding value in assessing DVR.

PMID- 21088213
TI  - Poor diets, abnormal breathing, and SIDS risk.

PMID- 21088214
TI  - MicroRNAs: playing a big role in explaining skeletal muscle adaptation?

PMID- 21088215
TI  - Links between progressive HIV-1 infection of humanized mice and viral
      neuropathogenesis.
AB  - Few rodent models of human immunodeficiency virus type one (HIV-1) infection can
      reflect the course of viral infection in humans. To this end, we investigated the
      relationships between progressive HIV-1 infection, immune compromise, and
      neuroinflammatory responses in NOD/scid-IL-2Rgamma(c)(null) mice reconstituted
      with human hematopoietic CD34(+) stem cells. Human blood-borne macrophages
      repopulated the meninges and perivascular spaces of chimeric animals. Viral
      infection in lymphoid tissue led to the accelerated entry of human cells into the
      brain, marked neuroinflammation, and HIV-1 replication in human mononuclear
      phagocytes. A meningitis and less commonly an encephalitis followed cM-T807
      antibody-mediated CD8(+) cell depletion. We conclude that HIV-1-infected NOD/scid
      IL-2Rgamma(c)(null) humanized mice can, at least in part, recapitulate lentiviral
      neuropathobiology. This model of neuroAIDS reflects the virological,
      immunological, and early disease-associated neuropathological components of human
      disease.

PMID- 21088216
TI  - CD40.FasL and CTLA-4.FasL fusion proteins induce apoptosis in malignant cell
      lines by dual signaling.
AB  - Evolution of apoptosis resistance in both lymphoma and leukemia cells is well
      documented, and induction of apoptosis in malignant cells is a major goal of
      cancer therapy. Up-regulation of anti-apoptotic signals is one of the mechanisms
      whereby resistance to apoptosis emerges. We have previously described the fusion
      proteins CD40.FasL and CTLA-4.FasL, which are formed from two functional membrane
      proteins and induce apoptosis of activated T cells. The present study explores
      the potential use of CD40.FasL and CTLA-4.FasL for the killing of malignant cells
      of lymphatic origin. Using malignant B and T cell lines that differ in surface
      expression of costimulatory molecules, we found that CTLA-4.FasL induces
      effective apoptosis of cells expressing CD95 and activates caspases 3, 8, and 9.
      Only B7-expressing B cells responded to CTLA-4.FasL with rapid abrogation of
      cFLIP expression. CD40.FasL effectively killed only the T cells that express high
      levels of CD40L in addition to CD95. In these cells, CD40.FasL significantly
      diminished cFLIP expression. Importantly, each of the fusion proteins is more
      potent than its respective components parts, alone or in combination. Thus, the
      proteins with their two functional ends deliver a pro-apoptotic signal and, in
      parallel, inhibit an anti-apoptotic signal, thus optimizing the wanted, death
      inducing effect. Therefore, these proteins emerge as promising agents to be used
      for targeted and specific tumor cell killing.

PMID- 21088217
TI  - A Western-type diet accelerates tumor progression in an autochthonous mouse model
      of prostate cancer.
AB  - Epidemiological studies have provided evidence suggesting an important role for
      diet and obesity in the development of cancer. Specifically, lipid nutrients of
      the diet have been identified as important regulators of tumor development and
      progression. In the present study, we have examined the role of dietary fat and
      cholesterol in the initiation and progression of prostate cancer using the well
      characterized TRAMP mouse model. Consumption of a Western-type diet--that is,
      enriched in both fat and cholesterol--accelerated prostate tumor incidence and
      tumor burden compared to mice fed a control chow diet. Furthermore, we also show
      that this diet increased the extent and the histological grade of prostate
      tumors. These findings were confirmed by the presence of increased levels of
      protein markers of advanced tumors in prostates obtained from animals fed a
      Western-type diet compared to those obtained from control animals. Increased lung
      metastases in animals fed a Western-type diet were also observed. In addition, we
      found that with a Western diet, animals bearing tumors presented with reduced
      plasma cholesterol levels compared with animals fed a control diet. Finally, we
      show that tumors obtained from animals fed a Western-type diet displayed
      increased expression of the high-density lipoprotein receptor SR-BI and increased
      angiogenesis. Taken together, our data suggest that dietary fat and cholesterol
      play an important role in the development of prostate cancer.

PMID- 21088219
TI  - Herbivore-induced and floral homoterpene volatiles are biosynthesized by a single
      P450 enzyme (CYP82G1) in Arabidopsis.
AB  - Terpene volatiles play important roles in plant-organism interactions as
      attractants of pollinators or as defense compounds against herbivores. Among the
      most common plant volatiles are homoterpenes, which are often emitted from night
      scented flowers and from aerial tissues upon herbivore attack. Homoterpene
      volatiles released from herbivore-damaged tissue are thought to contribute to
      indirect plant defense by attracting natural enemies of pests. Moreover,
      homoterpenes have been demonstrated to induce defensive responses in plant-plant
      interaction. Although early steps in the biosynthesis of homoterpenes have been
      elucidated, the identity of the enzyme responsible for the direct formation of
      these volatiles has remained unknown. Here, we demonstrate that CYP82G1
      (At3g25180), a cytochrome P450 monooxygenase of the Arabidopsis CYP82 family, is
      responsible for the breakdown of the C(20)-precursor (E,E)-geranyllinalool to the
      insect-induced C(16)-homoterpene (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene
      (TMTT). Recombinant CYP82G1 shows narrow substrate specificity for (E,E)
      geranyllinalool and its C(15)-analog (E)-nerolidol, which is converted to the
      respective C(11)-homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT). Homology
      based modeling and substrate docking support an oxidative bond cleavage of the
      alcohol substrate via syn-elimination of the polar head, together with an allylic
      C-5 hydrogen atom. CYP82G1 is constitutively expressed in Arabidopsis stems and
      inflorescences and shows highly coordinated herbivore-induced expression with
      geranyllinalool synthase in leaves depending on the F-box protein COI-1. CYP82G1
      represents a unique characterized enzyme in the plant CYP82 family with a
      function as a DMNT/TMTT homoterpene synthase.

PMID- 21088218
TI  - Transgenic mice overexpressing APP and transforming growth factor-beta1 feature
      cognitive and vascular hallmarks of Alzheimer's disease.
AB  - High brain levels of amyloid-beta (Abeta) and transforming growth factor-beta1
      (TGF-beta1) have been implicated in the cognitive and cerebrovascular alterations
      of Alzheimer's disease (AD). We sought to investigate the impact of combined
      increases in Abeta and TGF-beta1 on cerebrovascular, neuronal, and mnemonic
      function using transgenic mice overproducing these peptides (A/T mice). In
      particular, we measured cerebrovascular reactivity, evoked cerebral blood flow
      and glucose uptake during brain activation, cholinergic status, and spatial
      memory, along with cerebrovascular fibrosis, amyloidosis, and astrogliosis, and
      their evolution with age. An assessment of perfusion and metabolic responses was
      considered timely, given ongoing efforts for their validation as AD biomarkers.
      Relative to wild-type littermates, A/T mice displayed an early progressive
      decline in cerebrovascular dilatory ability, preserved contractility, and
      reduction in constitutive nitric oxide synthesis that establishes resting vessel
      tone. Altered levels of vasodilator-synthesizing enzymes and fibrotic proteins,
      resistance to antioxidant treatment, and unchanged levels of the antioxidant
      enzyme, superoxide dismutase-2, accompanied these impairments. A/T mice featured
      deficient neurovascular and neurometabolic coupling to whisker stimulation,
      cholinergic denervation, cerebral and cerebrovascular Abeta deposition, astrocyte
      activation, and impaired Morris water maze performance, which gained severity
      with age. The combined Abeta- and TGF-beta1-driven pathology recapitulates
      salient cerebrovascular, neuronal, and cognitive AD landmarks and yields a
      versatile model toward highly anticipated diagnostic and therapeutic tools for
      patients featuring Abeta and TGF-beta1 increments.

PMID- 21088220
TI  - Ca2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a
      receptor with guanylyl cyclase activity, and cGMP-activated Ca2+ channels.
AB  - A family of peptide signaling molecules (AtPeps) and their plasma membrane
      receptor AtPepR1 are known to act in pathogen-defense signaling cascades in
      plants. Little is currently known about the molecular mechanisms that link these
      signaling peptides and their receptor, a leucine-rich repeat receptor-like
      kinase, to downstream pathogen-defense responses. We identify some cellular
      activities of these molecules that provide the context for a model for their
      action in signaling cascades. AtPeps activate plasma membrane inwardly conducting
      Ca(2+) permeable channels in mesophyll cells, resulting in cytosolic Ca(2+)
      elevation. This activity is dependent on their receptor as well as a cyclic
      nucleotide-gated channel (CNGC2). We also show that the leucine-rich repeat
      receptor-like kinase receptor AtPepR1 has guanylyl cyclase activity, generating
      cGMP from GTP, and that cGMP can activate CNGC2-dependent cytosolic Ca(2+)
      elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3,
      and WRKY33) is mediated by the Ca(2+) signaling pathway associated with AtPep
      peptides and their receptor. The work presented here indicates that extracellular
      AtPeps, which can act as danger-associated molecular patterns, signal by
      interaction with their receptor, AtPepR1, a plasma membrane protein that can
      generate cGMP. Downstream from AtPep and AtPepR1 in a signaling cascade, the cGMP
      activated channel CNGC2 is involved in AtPep- and AtPepR1-dependent inward Ca(2+)
      conductance and resulting cytosolic Ca(2+) elevation. The signaling cascade
      initiated by AtPeps leads to expression of pathogen-defense genes in a Ca(2+)
      dependent manner.

PMID- 21088221
TI  - Evolution of diverse mechanisms for protecting chromosome ends by Drosophila TART
      telomere retrotransposons.
AB  - The retrotransposons HeT-A, TART, and TAHRE, which maintain Drosophila telomeres,
      transpose specifically onto chromosome ends to form long arrays that extend the
      chromosome and compensate for terminal loss. Because they transpose by target
      primed reverse transcription, each element is oriented so that its 5' end serves
      as the extreme end of the chromosome until another element transposes to occupy
      the terminal position. Thus 5' sequences are at risk for terminal erosion while
      the element is at the chromosome end. Here we report that TART elements in
      Drosophila melanogaster and Drosophila virilis show species-specific innovations
      in promoter architecture that buffer loss of sequence exposed at chromosome ends.
      The two elements have evolved different ways to effect this protection. The D.
      virilis TART (TART(vir)) promoter is found in the 3' UTR of the element directly
      upstream of the element transcribed. Transcription starts within the upstream
      element so that a "Tag" of extra sequence is added to the 5' end of the newly
      transcribed RNA. This Tag provides expendable sequence to buffer end erosion of
      essential 5' sequence after the RNA is reverse transcribed onto the chromosome.
      In contrast, the D. melanogaster TART (TART(mel)) promoter initiates
      transcription deep within the 5' UTR, but the element is able to replace and
      extend the 5' UTR sequence by copying sequence from its 3' UTR, we believe while
      being reverse transcribed onto the chromosome end. Astonishingly, end-protection
      in TART(vir) and HeT-A(mel) are essentially identical (using Tags), whereas HeT
      A(vir) is clearly protected from end erosion by an as-yet-unspecified program.

PMID- 21088222
TI  - Transcription factor E4F1 is essential for epidermal stem cell maintenance and
      skin homeostasis.
AB  - A growing body of evidence suggests that the multifunctional protein E4F1 is
      involved in signaling pathways that play essential roles during normal
      development and tumorigenesis. We generated E4F1 conditional knockout mice to
      address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in
      the entire skin or in the basal compartment of the epidermis induces skin
      homeostasis defects, as evidenced by transient hyperplasia in the interfollicular
      epithelium and alteration of keratinocyte differentiation, followed by loss of
      cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters
      clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion
      of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant
      skin result, at least in part, from cell-autonomous alterations in ESC
      maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1
      overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice
      is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies.
      Our data identify a regulatory axis essential for ESC-dependent skin homeostasis
      implicating E4F1 and the Bmi1-Arf-p53 pathway.

PMID- 21088224
TI  - The novel UDP glycosyltransferase 3A2: cloning, catalytic properties, and tissue
      distribution.
AB  - The human UDP glycosyltransferase (UGT) 3A family is one of three families
      involved in the metabolism of small lipophilic compounds. Members of these
      families catalyze the addition of sugar residues to chemicals, which enhances
      their excretion from the body. The UGT1 and UGT2 family members primarily use UDP
      glucuronic acid to glucuronidate numerous compounds, such as steroids, bile
      acids, and therapeutic drugs. We showed recently that UGT3A1, the first member of
      the UGT3 family to be characterized, is unusual in using UDP N-acetylglucosamine
      as sugar donor, rather than UDP glucuronic acid or other UDP sugar nucleotides (J
      Biol Chem 283:36205-36210, 2008). Here, we report the cloning, expression, and
      characterization of UGT3A2, the second member of the UGT3 family. Like UGT3A1,
      UGT3A2 is inactive with UDP glucuronic acid as sugar donor. However, in contrast
      to UGT3A1, UGT3A2 uses both UDP glucose and UDP xylose but not UDP N
      acetylglucosamine to glycosidate a broad range of substrates including 4
      methylumbelliferone, 1-hydroxypyrene, bioflavones, and estrogens. It has low
      activity toward bile acids and androgens. UGT3A2 transcripts are found in the
      thymus, testis, and kidney but are barely detectable in the liver and
      gastrointestinal tract. The low expression of UGT3A2 in the latter, which are the
      main organs of drug metabolism, suggests that UGT3A2 has a more selective role in
      protecting the organs in which it is expressed against toxic insult rather than a
      more generalized role in drug metabolism. The broad substrate and novel UDP sugar
      specificity of UGT3A2 would be advantageous for such a function.

PMID- 21088225
TI  - Different effects of the different natural CC chemokine receptor 2b ligands on
      beta-arrestin recruitment, Galphai signaling, and receptor internalization.
AB  - The chemokine receptor CCR2, which has been implicated in a variety of
      inflammatory, autoimmune, and cardiovascular conditions, binds several natural
      chemokine ligands. Here, we assessed the recruitment of beta-arrestin to CCR2 in
      response to these ligands using bioluminescence resonance energy transfer
      technology. Compared with CCL2, which was considered as a full agonist, other
      CCR2 ligands were partial agonists with reduced efficacy and potency. Agonist
      potencies were not a function of their affinity for CCR2. Efficacy of arrestin
      recruitment matched that of agonist-induced CCR2 internalization. Although the
      potency and efficacy rank orders of the ligands in arrestin recruitment were
      similar to those observed for Galpha(i1) activation, arrestin recruitment was at
      least in part resistant to Galpha(i/o)-inactivating pertussis toxin, suggesting
      partial independence from Galpha(i/o). The degree of pertussis toxin resistance
      of arrestin recruitment was different between the chemokines. Moreover,
      qualitative differences between the arrestin responses to the different ligands
      were identified in the stability of the response: although CCL7-induced arrestin
      recruitment had a half-life of less than 15 min, CCL8 and CCL13 induced stable
      CCR2-arrestin interactions. Finally, the ligands stabilized different
      conformations of the CCR2 homodimer. Our results support the validity of models
      for receptor-ligand interactions in which different ligands stabilize different
      receptor conformations also for endogenous receptor ligands, with corresponding
      implications for drug development targeting CCR2.

PMID- 21088223
TI  - Health benefits and cost-effectiveness of primary genetic screening for Lynch
      syndrome in the general population.
AB  - In current clinical practice, genetic testing to detect Lynch syndrome mutations
      ideally begins with diagnostic testing of an individual affected with cancer
      before offering predictive testing to at-risk relatives. An alternative strategy
      that warrants exploration involves screening unaffected individuals via
      demographic and family histories, and offering genetic testing to those
      individuals whose risks for carrying a mutation exceed a selected threshold.
      Whether this approach would improve health outcomes in a manner that is cost
      effective relative to current standards of care has yet to be demonstrated. To do
      so, we developed a simulation framework that integrated models of colorectal and
      endometrial cancers with a 5-generation family history model to predict health
      and economic outcomes of 20 primary screening strategies (at a wide range of
      compliance levels) aimed at detecting individuals with mismatch repair gene
      mutations and their at-risk relatives. These strategies were characterized by (i)
      different screening ages for starting risk assessment and (ii) different risk
      thresholds above which to implement genetic testing. For each strategy, 100,000
      simulated individuals, representative of the U.S. population, were followed from
      the age of 20, and the outcomes were compared with current practice. Findings
      indicated that risk assessment starting at ages 25, 30, or 35, followed by
      genetic testing of those with mutation risks exceeding 5%, reduced colorectal and
      endometrial cancer incidence in mutation carriers by approximately 12.4% and
      8.8%, respectively. For a population of 100,000 individuals containing 392
      mutation carriers, this strategy increased quality-adjusted life-years (QALY) by
      approximately 135 with an average cost-effectiveness ratio of $26,000 per QALY.
      The cost-effectiveness of screening for mismatch repair gene mutations is
      comparable to that of accepted cancer screening activities in the general
      population such as colorectal cancer screening, cervical cancer screening, and
      breast cancer screening. These results suggest that primary screening of
      individuals for mismatch repair gene mutations, starting with risk assessment
      between the ages of 25 and 35, followed by genetic testing of those whose risk
      exceeds 5%, is a strategy that could improve health outcomes in a cost-effective
      manner relative to current practice.

PMID- 21088226
TI  - Does enhanced photosynthesis enhance growth? Lessons learned from CO2 enrichment
      studies.

PMID- 21088227
TI  - Genetic dissection of barley morphology and development.
AB  - Since the early 20th century, barley (Hordeum vulgare) has been a model for
      investigating the effects of physical and chemical mutagens and for exploring the
      potential of mutation breeding in crop improvement. As a consequence, extensive
      and well-characterized collections of morphological and developmental mutants
      have been assembled that represent a valuable resource for exploring a wide range
      of complex and fundamental biological processes. We constructed a collection of
      881 backcrossed lines containing mutant alleles that induce a majority of the
      morphological and developmental variation described in this species. After
      genotyping these lines with up to 3,072 single nucleotide polymorphisms,
      comparison to their recurrent parent defined the genetic location of 426 mutant
      alleles to chromosomal segments, each representing on average <3% of the barley
      genetic map. We show how the gene content in these segments can be predicted
      through conservation of synteny with model cereal genomes, providing a route to
      rapid gene identification.

PMID- 21088228
TI  - Manganese limitation induces changes in the activity and in the organization of
      photosynthetic complexes in the cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - Manganese (Mn) ions are essential for oxygen evolution activity in
      photoautotrophs. In this paper, we demonstrate the dynamic response of the
      photosynthetic apparatus to changes in Mn bioavailability in cyanobacteria.
      Cultures of the cyanobacterium Synechocystis PCC 6803 could grow on Mn
      concentrations as low as 100 nm without any observable effect on their
      physiology. Below this threshold, a decline in the photochemical activity of
      photosystem II (PSII) occurred, as evident by lower oxygen evolution rates, lower
      maximal photosynthetic yield of PSII values, and faster Q(A) reoxidation rates.
      In 77 K chlorophyll fluorescence spectroscopy, a peak at 682 nm was observed.
      After ruling out the contribution of phycobilisome and iron stress-induced IsiA
      proteins, this band was attributed to the accumulation of partially assembled
      PSII. Surprisingly, the increase in the 682-nm peak was paralleled by a decrease
      in the 720-nm peak, dominated by PSI fluorescence. The effect on PSI was
      confirmed by measurements of the P(700) photochemical activity. The loss of
      activity was the result of two processes: loss of PSI core proteins and changes
      in the organization of PSI complexes. Blue native-polyacrylamide gel
      electrophoresis analysis revealed a Mn limitation-dependent dissociation of PSI
      trimers into monomers. The sensitive range for changes in the organization of the
      photosynthetic apparatus overlaps with the range of Mn concentrations measured in
      natural environments. We suggest that the ability to manipulate PSI content and
      organization allows cyanobacteria to balance electron transport rates between the
      photosystems. At naturally occurring Mn concentrations, such a mechanism will
      provide important protection against light-induced damage.

PMID- 21088229
TI  - DNA fragmentation in morphologically normal spermatozoa: how much should we be
      concerned in the ICSI era?
AB  - Intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of male
      infertility. However, there are still unanswered questions about the safety of
      this technique. During ICSI, only morphologically normal and motile spermatozoa
      are typically used to fertilize an oocyte. We recently reported that in infertile
      men, spermatozoa with apparently normal morphology may have DNA fragmentation.
      This finding consequently raised the possibility that spermatozoa with normal
      shaped appearance but with DNA fragmentation could be mistakenly selected to
      fertilize oocytes during ICSI. This concern became more clinically significant
      following the subsequent finding that the presence of an increased proportion of
      normal spermatozoa with damaged DNA was negatively associated with embryo quality
      and pregnancy outcome after ICSI. Herein, we propose and discuss the hypothesis
      that the examination of DNA integrity in the subpopulation of highly motile
      (hence viable) and morphologically normal cells (and not in the total sperm
      population) may provide optimized information in prediction of ICSI success. More
      importantly, this new way of evaluation may provide reassurance about genomic
      normalcy and minimal risk of transmission of genetic disease and guide the
      development of improved methods of selection of spermatozoa with intact DNA to be
      used in assisted reproduction.

PMID- 21088230
TI  - Effects of chemotherapeutic agents for testicular cancer on rat spermatogonial
      stem/progenitor cells.
AB  - Spermatogonial stem cells (SSCs) are responsible for the production of
      spermatozoa throughout adulthood and for the recovery of spermatogenesis
      following exposure to cytotoxic agents. Previously, we have shown that the
      combined administration of bleomycin, etoposide, and cisplatin (BEP) used in the
      treatment of testicular cancer causes impaired spermatogenesis and reduced sperm
      production in the rat. However, definitive evidence about the potential impact of
      such chemotherapy on SSCs is still lacking. The objective of this study was to
      determine whether chronic exposure to BEP treatment causes adverse effects on rat
      SSC activity. We first investigated the effects of BEP treatment on the clonal
      organization of undifferentiated spermatogonia by staining whole-mount
      preparations of rat seminiferous tubules for GFRA1 and ZBTB16 (previously known
      as PLZF), 2 established markers of undifferentiated spermatogonia. We found that
      BEP treatment drastically reduced the number of A-aligned spermatogonia while
      sparing A-single and A-paired cells from the effect. Next, we determined the SSC
      activity following BEP exposure. Adult transgenic rats carrying EGFP expression
      in the germ line were treated with BEP for 9 weeks, and SSCs were quantified
      using spermatogonial transplantation. We found that BEP treatment significantly
      decreased SSC numbers, which were restored to the control level after a 9-week
      recovery period. These results demonstrate that BEP treatment transiently affects
      the activity of rat SSCs.

PMID- 21088231
TI  - GLUTs and mammalian sperm metabolism.
AB  - Mammalian cells use glucides as a substrate that can be catabolized through
      glycolitic pathways or oxidative phosphorylation, used as a source of reducing
      potential, or used for anabolic aims. An important role in supplying cells with
      energy is played by different membrane proteins that can actively (sodium
      dependent glucose transporters) or passively (glucose transporters; GLUT)
      transport hexoses through the lipidic bilayer. In particular, GLUTs are a family
      of 13 proteins that facilitate the transport of sugars and have a peculiar
      distribution in different tissues as well as a particular affinity for
      substrates. These proteins are also present in mature sperm cells, which, in
      fact, need carriers for uptake energetic sources that are important for
      maintaining cell basic activity as well as specific functions, such as motility
      and fertilization ability. Likewise, several GLUTs have been studied in various
      mammalian species (man, bull, rat, mouse, boar, dog, stallion, and donkey) to
      point out both their actual presence or absence and their localization on plasma
      membrane. The aim of this work is to give an overall picture of the studies
      available on GLUTs in mammalian spermatozoa at this moment, pointing out the
      species peculiarity, the possible role of these proteins, and the potential
      future research on this item.

PMID- 21088232
TI  - Osmotic stress stimulates phosphorylation and cellular expression of heat shock
      proteins in rhesus macaque sperm.
AB  - The cryosurvival of sperm requires cell signaling mechanisms to adapt to
      anisotonic conditions during the freezing and thawing process. Chaperone proteins
      heat shock protein 70 (HSP 70) and heat shock protein 90 (HSP 90; recently
      renamed HSPA and HSPC, respectively) facilitate some of these cell signaling
      events in somatic cells. Sperm were evaluated for their cellular expression and
      levels of phosphorylation of both HSP 70 and HSP 90 under anisotonic conditions
      as a potential model for cell signaling during the cryopreservation of macaque
      spermatozoa. In order to monitor the level of stress, the motility and viability
      parameters were evaluated at various time points. Cells were then either prepared
      for phosphoprotein enrichment or indirect immunocytochemistry. As controls, the
      phosphoserine, phosphothreonine, and phosphotyrosine levels were measured under
      capacitation and cryopreservation conditions and were compared with the
      phosphoprotein levels expressed under osmotic conditions. As expected, there was
      an increase in the level of tyrosine phosphorylation under capacitation and
      cryopreservation conditions. There was also a significant increase in the level
      of all phosphoproteins under hyperosmotic conditions. There was no change in the
      level of expression of HSP 70 or 90 under osmotic stress conditions as measured
      by Western blot. The enrichment of phosphoproteins followed by Western
      immunoblotting revealed an increase in the phosphorylation of HSP 70 but not HSP
      90 under osmotic stress conditions. Indirect immunofluorescence localized HSP 70
      to the postacrosomal region of sperm, and the level of membrane expression of HSP
      70 was significantly affected by anisotonic conditions, as measured by flow
      cytometry. Taken together, these results suggest a differential role for HSP 70
      and HSP 90 during osmotic stress conditions in rhesus macaque sperm.

PMID- 21088233
TI  - Effects of carbon monoxide on ion transport across rat distal colon.
AB  - The aim of the present study was to investigate whether carbon monoxide (CO)
      induces changes in ion transport across the distal colon of rats and to study the
      mechanisms involved. In Ussing chamber experiments,
      tricarbonyldichlororuthenium(II) dimer (CORM-2), a CO donor, evoked a
      concentration-dependent increase in short-circuit current (I(sc)). A maximal
      response was achieved at a concentration of 2.5.10(-4) mol/l. Repeated
      application of CORM-2 resulted in a pronounced desensitization of the tissue.
      Anion substitution experiments suggest that a secretion of Cl(-) and HCO(3)(-)
      underlie the CORM-2-induced current. Glibenclamide, a blocker of the apical
      cystic fibrosis transmembrane regulator channel, inhibited the I(sc) induced by
      the CO donor. Similarly, bumetanide, a blocker of the basolateral Na(+)-K(+)-2Cl(
      ) cotransporter, combined with 4-acetamido-4'-isothiocyanato-stilbene-2,2'
      disulfonic acid sodium salt, an inhibitor of the basolateral Cl(-)/HCO(3)(-)
      exchanger, inhibited the CORM-2-induced I(sc). Membrane permeabilization
      experiments indicated an activation of basolateral K(+) and apical Cl(-) channels
      by CORM-2. A partial inhibition by the neurotoxin, tetrodotoxin, suggests the
      involvement of secretomotor neurons in this response. In imaging experiments at
      fura-2-loaded colonic crypts, CORM-2 induced an increase of the cytosolic Ca(2+)
      concentration. This increase depended on the influx of extracellular Ca(2+), but
      not on the release of Ca(2+) from intracellular stores. Both enzymes for CO
      production, heme oxygenase I and II, are expressed in the colon as observed
      immunohistochemically and by RT-PCR. Consequently, endogenous CO might be a
      physiological modulator of colonic ion transport.

PMID- 21088235
TI  - A stem cell marker-expressing subset of enteroendocrine cells resides at the
      crypt base in the small intestine.
AB  - The spatial orientation of the enteroendocrine cells along the crypt-villus axis
      is closely associated with their differentiation in the intestine. Here we
      studied this relationship using primary duodenal crypts and an ex vivo organoid
      system established from cholecystokinin-green fluorescent protein (CCK-GFP)
      transgenic mice. In the primary duodenal crypts, GFP+ cells were found not only
      in the upper crypt but also at the crypt base, where the stem cells reside. Many
      GFP+ cells below +4 position were positive for the putative intestinal stem cell
      markers, leucine-rich repeat-containing G protein-coupled receptor 5, CD133, and
      doublecortin and CaM kinase-like-1, and also for the neuroendocrine transcription
      factor neurogenin 3. However, these cells were neither stem nor transient
      amplifying precursor cells because they were negative for both Ki-67 and phospho
      Histone H3 and positive for the mature endocrine marker chromogranin A.
      Furthermore, these cells expressed multiple endocrine hormones. Tracking of GFP+
      cells in the organoids from CCK-GFP mice indicated that GFP+ cells were first
      observed around the +4 position, some of which localized to the crypt base later
      in the culture period. These results suggest that a subset of enteroendocrine
      cells migrates down to the crypt base or stays localized at the crypt base, where
      they express stem and postmitotic endocrine markers. Further investigation of the
      function of this subset may provide novel insights into the genesis and
      development of enteroendocrine cells as well as enteroendocrine tumorigenesis.

PMID- 21088234
TI  - Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in
      mammalian intestine.
AB  - The inflammasome is a multiprotein complex whose formation is triggered when a
      NOD-like receptor binds a pathogen ligand, resulting in activated caspase-1,
      which converts certain interleukins (IL-1beta, IL-18, and IL-33) to their active
      forms. There is currently no information on regulation of this system around the
      time of birth. We employed transcript profiling of fetal rat intestinal and lung
      RNA at embryonic days 16 (E16) and 20 (E20) with out-of-sample validation using
      quantitative RT-PCR. Transcript profiling and quantitative RT-PCR demonstrated
      that transcripts of core components of the NOD-like receptor Nlrp6 inflammasome
      (Nlrp6, Pycard, Caspase-1) and one of its substrates, IL-18, were increased at
      E20 compared with E16 in fetal intestine and not lung. Immunohistochemistry
      demonstrated increased Pycard in intestinal epithelium. Western blotting
      demonstrated that IL-18 was undetectable at E16, clearly detectable at E20 in its
      inactive form, and detectable postnatally in both its inactive and active form.
      Dramatic upregulation of IL-18 was also observed in the fetal sheep jejunum in
      late gestation (P = 0.006). Transcription factor binding analysis of the rat
      array data revealed an overrepresentation of nuclear transcription factor binding
      sites peroxisome proliferator-activated receptor gamma (PPAR-gamma) and retinoid
      X receptor-alpha and chicken ovalbumin upstream promoter transcription factor 1
      in the region 1,000 bp upstream of the transcription start site. Rosiglitazone, a
      PPAR-gamma agonist, more than doubled levels of NLRP6 mRNA in human intestinal
      epithelial (Caco2) cells. These observations provide the first evidence, to our
      knowledge, linking activity of PPAR-gamma to expression of a NOD-like receptor
      and adds to a growing body of evidence linking pattern recognition receptors of
      the innate immune system and intestinal colonization.

PMID- 21088236
TI  - Snail1 transcription factor is a critical mediator of hepatic stellate cell
      activation following hepatic injury.
AB  - Following liver injury, the wound-healing process is characterized by hepatic
      stellate cell (HSC) activation from the quiescent fat-storing phenotype to a
      highly proliferative myofibroblast-like phenotype. Snail1 is a transcription
      factor best known for its ability to trigger epithelial-mesenchymal transition,
      to influence mesoderm formation during embryonic development, and to favor cell
      survival. In this study, we evaluated the expression of Snail1 in experimental
      and human liver fibrosis and analyzed its role in the HSC transdifferentiation
      process. Liver samples from patients with liver fibrosis and from mice treated by
      either carbon tetrachloride (CCl(4)) or thioacetamide (TAA) were evaluated for
      mRNA expression of Snail1. The transcription factor expression was investigated
      by immunostaining and real-time quantitative RT-PCR (qRT-PCR) on in vitro and in
      vivo activated murine HSC. Snail1 knockdown studies on cultured HSC and on CCl(4)
      treated mice were performed by adenoviral delivery of short-hairpin RNA;
      activation-related genes were quantitated by real-time qRT-PCR and Western
      blotting. Snail1 mRNA expression resulted upregulated in murine experimental
      models of liver injury and in human hepatic fibrosis. In vitro studies showed
      that Snail1 is expressed by HSC and that its transcription is augmented in in
      vitro and in vivo activated HSC compared with quiescent HSC. At the protein
      level, we could observe the nuclear translocation of Snail1 in activated HSC.
      Snail1 knockdown resulted in the downregulation of activation-related genes both
      in vitro and in vivo. Our data support a role for Snail1 transcription factor in
      the hepatic wound-healing response and its involvement in the HSC
      transdifferentiation process.

PMID- 21088239
TI  - Immunodepression after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: immunodepression after stroke is associated with
      complications like high infection rate, but its role in aneurysmal subarachnoid
      hemorrhage (aSAH) is unclear. This pilot study aimed to assess the presence of
      immunodepression and its association with infections after aSAH. METHODS: sixteen
      aSAH patients were enrolled in a prospective study on immune function in a single
      institution. Detailed immune monitoring (peripheral blood leukocyte subsets,
      monocyte human leukocyte antigen-DR expression, ex vivo lipopolysaccharide
      induced monocytic, Concanavalin A-induced lymphocytic cytokine secretion) was
      performed until day 10 after aSAH. Occurrence of infection was assessed within 14
      days after aSAH. RESULTS: sixteen consecutive aSAH patients (53.1 +/- 10.2 years;
      mean +/- SD) met the inclusion criteria, classified as asymptomatic (World
      Federation of Neurological Surgeons; median, 1; quartile, 1-1; n=7) and
      symptomatic (median, 4; quartile, 3-5; n=9), all presenting with acute
      neurological deficits, and 5 of these had additional delayed cerebral ischemia. T
      lymphopenia, impaired ex vivo lymphocytic/monocytic cytokine secretion, and
      decreased monocyte human leukocyte antigen-DR expression occurred over all World
      Federation of Neurological Surgeons grades but persisted beyond day 3 only in
      symptomatic patients. Pneumonia (67%; P=0.011) was more frequent in symptomatic
      patients. Already at day 1, patients with pneumonia showed significantly lower T
      cell counts and mitogen-induced interferon-gamma production compared to patients
      without infections. CONCLUSIONS: a pronounced SAH-induced immunodepression was
      observed early after aSAH but persisted only in symptomatic patients.
      Immunodepression was associated with a high incidence of pneumonia. Early
      diagnosis of immunodepression might allow targeted treatment to prevent
      infectious complications after aSAH.

PMID- 21088238
TI  - Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a
      rat model.
AB  - Patients with chemotherapy-induced gastrointestinal mucositis suffer from
      anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition.
      When the intestinal function during mucositis would be known, a rational feeding
      strategy might improve the nutritional state, accelerate recuperation, and
      increase survival of mucositis patients. We developed a methotrexate (MTX)
      induced mucositis rat model to study nutrient digestion and absorption. To
      determine lactose digestion and absorption of its derivative glucose during
      mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl
      (controls). Four days later, we orally administered trace amounts of [1
      (13)C]lactose and [U-(13)C]glucose and quantified the appearance of labeled
      glucose in the blood for 3 h. Finally, we determined plasma citrulline level and
      harvested the small intestine to assess histology, myeloperoxidase level,
      glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX
      treated rats showed profound villus atrophy and epithelial damage. During the
      experimental period, the absorption of lactose-derived [1-(13)C]glucose was 4.2
      fold decreased in MTX-treated rats compared with controls (P < 0.01). Lactose
      derived [1-(13)C]glucose absorption correlated strongly with villus length (rho =
      0.86, P < 0.001) and with plasma citrulline level (rho = 0.81, P < 0.001). MTX
      treatment decreased jejunal lactase activity (19.5-fold, P < 0.01) and
      immunohistochemical protein and mRNA expression (39.7-fold, P < 0.01) compared
      with controls. Interestingly, MTX treatment did not affect the absorption of [U
      (13)C]glucose during the experimental period. We conclude that lactose digestion
      is severely decreased during mucositis while glucose absorption is still intact,
      when supplied in trace amounts. Plasma citrulline level might be a useful
      objective, noninvasive marker for lactose maldigestion during mucositis in
      clinic.

PMID- 21088240
TI  - Effect of baseline CT scan appearance and time to recanalization on clinical
      outcomes in endovascular thrombectomy of acute ischemic strokes.
AB  - BACKGROUND AND PURPOSE: the Penumbra Pivotal Stroke Trial reported a 25% good
      outcome (modified Rankin scale score <= 2) despite an 81% recanalization rate. We
      evaluated the association of a favorable initial noncontrast CT and a short time
      to recanalization in predicting good outcome. METHODS: data were from the
      Penumbra Pivotal Stroke Trial. Baseline scans were evaluated by 2 experienced
      readers blinded to outcomes using ASPECTS. ASPECTS scores were dichotomized into
      >7 and <= 7 for primary analysis. Data on degree of recanalization based on
      thrombolysis in myocardial infarction scores, stroke onset to recanalization, and
      CT to recanalization times were obtained. Primary outcome was modified Rankin
      scale score <= 2 at 3 months. RESULTS: median baseline NIHSS was 18 (range, 8-34)
      and median baseline ASPECTS score was 6 (range, 0-10); 81.2% achieved
      recanalization (thrombolysis in myocardial infarction, 2-3) and (27.7%) achieved
      good outcome. Good outcome was significantly higher in the ASPECTS score >7 group
      when compared to the ASPECTS score <= 7 group (50% vs 15%; RR, 3.3; 95% CI, 1.6
      6.8; P=0.0001). No patient with an ASPECTS score <= 4 (n=28) or without
      recanalization (n=16) had a good outcome. There was an interaction between
      baseline ASPECTS score (>7 and <= 7) and onset to recanalization time (<= 300
      minutes and >300 minutes) in predicting good outcome (P=0.06). CONCLUSIONS:
      patients with baseline CT ASPECTS score <= 4 do not benefit from recanalization.
      Fast recanalization may benefit patients with evident damage on the CT scan
      (ASPECTS score >4). Overall, patients benefit the most with early recanalization
      and a favorable baseline CT scan (ASPECTS score >7).

PMID- 21088237
TI  - Advances in the understanding of mineral and bone metabolism in inflammatory
      bowel diseases.
AB  - Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect
      bone metabolism and are frequently associated with the presence of osteopenia,
      osteoporosis, and increased risk of fractures. Although several mechanisms may
      contribute to skeletal abnormalities in IBD patients, inflammation and
      inflammatory mediators such as TNF, IL-1beta, and IL-6 may be the most critical.
      It is not clear whether the changes in bone metabolism leading to decreased
      mineral density are the result of decreased bone formation, increased bone
      resorption, or both, with varying results reported in experimental models of IBD
      and in pediatric and adult IBD patients. New data, including our own, challenge
      the conventional views, and contributes to the unraveling of an increasingly
      complex network of interactions leading to the inflammation-associated bone loss.
      Since nutritional interventions (dietary calcium and vitamin D supplementation)
      are of limited efficacy in IBD patients, understanding the pathophysiology of
      osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical
      for the correct choice of available treatments or the development of new targeted
      therapies. In this review, we discuss current concepts explaining the effects of
      inflammation, inflammatory mediators and their signaling effectors on calcium and
      phosphate homeostasis, osteoblast and osteoclast function, and the potential
      limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD.

PMID- 21088241
TI  - Computed tomographic angiography and venography for young or nonhypertensive
      patients with acute spontaneous intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: we compared the effectiveness of using computed
      tomographic angiography and venography (CTAV) with digital subtraction
      angiography (DSA) in young or nonhypertensive patients with acute spontaneous
      intracerebral hemorrhage. METHODS: we prospectively recruited 109 young (age
      between 18 and 45 years) or nonhypertensive patients with acute spontaneous
      intracerebral hemorrhage for this comparative study. All patients had CTAV using
      multidetector CT with 64 detectors. They were then scheduled to have catheter
      angiography the next day. Radiological data were collected for blinded analysis.
      RESULTS: DSA-positive pathologies causing hemorrhage were identified in 37 (33%)
      patients, which included cerebral arteriovenous malformation in 22 cases. The
      positive and negative predictive values of CTAV for DSA-positive pathologies
      causing hemorrhage were 97.3% (95% CI, 88.3%-99.9%) and 100% (95% CI, 95.9%
      100%), respectively. CONCLUSIONS: CTAV was able to detect DSA-positive
      pathologies causing acute spontaneous intracerebral hemorrhage in young (age
      between 18 and 45 years) or nonhypertensive patients with high positive and
      negative predictive values.

PMID- 21088243
TI  - Ipsilateral stroke in a patient with horizontal gaze palsy with progressive
      scoliosis and a subcortical infarct.
AB  - BACKGROUND AND PURPOSE: horizontal gaze palsy with progressive scoliosis (HGPPS)
      is a rare congenital disorder caused by mutation in the ROBO3 gene. It is
      characterized by absent horizontal eye movements with progressive scoliosis
      developing in childhood and adolescence. To our knowledge, both diffusion tensor
      imaging evaluation in HGPPS patients who present with stroke and truncating stop
      codon mutation in the ROBO3 gene have yet to be reported. SUMMARY OF CASE: we
      present a man with HGPPS who experienced a left pure motor stroke as a result of
      a left corona radiata infarct on diffusion-weighted imaging. Diffusion tensor
      imaging tractography confirmed the presence of uncrossed corticospinal tracts,
      accounting for the ipsilateral deficit. He was also found to possess a novel
      ROBO3 stop codon mutation on genetic testing. CONCLUSIONS: patients with HGPPS
      may present with stroke symptoms on the ipsilateral side of the infarct in view
      of uncrossed corticospinal tracts. Truncating mutation in ROBO3 may provide
      additional pathophysiologic insights.

PMID- 21088242
TI  - Sickle cell disease and transcranial Doppler imaging: inter-hemispheric
      differences in blood flow Doppler parameters.
AB  - BACKGROUND AND PURPOSE: to establish reference values of interhemispheric
      differences and ratios of blood flow Doppler parameters in the terminal internal
      carotid artery, middle cerebral artery, and anterior cerebral artery in children
      with sickle cell anemia. METHODS: fifty-seven out of 74 recruited children (mean
      age, 7.8 +/- 3.4 years; range limits, 3-14 years), who were free of neurological
      deficits and intracranial narrowing detectable by MRA and had flow velocities
      <170 cm/s by conventional transcranial Doppler ultrasound, underwent transcranial
      color-coded duplex ultrasonography. Reference limits of flow parameters corrected
      and uncorrected for the angle of insonation were estimated using tolerance
      intervals, with P=0.90 for all possible data values from 95% of a population.
      RESULTS: reference limits for left-to-right differences in cm/s in the mean angle
      corrected and uncorrected flow velocities were -56 to 53 and -72 to 75 for middle
      cerebral artery, -49 to 57 and -81 to 91 for anterior cerebral artery, and -55 to
      64 and -73 to 78 for terminal internal carotid artery, respectively. Respective
      reference limits for left-to-right velocity ratios were 0.31 to 1.84 and 0.38 to
      1.75 for middle cerebral artery, 0.48 to 2.99 and 0.46 to 2.89 for anterior
      cerebral artery, and 0.61 to 2.56 and 0.56 to 2.23 for terminal internal carotid
      artery. CONCLUSIONS: the study provides reference limits of interhemispheric
      differences and ratios of blood flow Doppler parameters that may be helpful in
      identification of intracranial arterial narrowing in children with sickle cell
      disease undergoing ultrasound screening for stroke prevention.

PMID- 21088244
TI  - Delayed anti-nogo-a therapy improves function after chronic stroke in adult rats.
AB  - BACKGROUND AND PURPOSE: we have shown that anti-Nogo-A immunotherapy to
      neutralize the neurite growth inhibitory protein Nogo-A results in functional
      improvement and enhanced plasticity after ischemic stroke in the adult rat. The
      present study investigated whether functional improvement and neuronal plasticity
      can be induced by this immunotherapy when administered to the chronic stroke
      impaired rat. METHODS: adult rats were trained to perform the skilled forelimb
      reaching test, followed by permanent middle cerebral artery occlusion to impair
      the preferred forelimb. Nine weeks after stroke, animals showing a profound
      deficit were randomly distributed to 3 groups: no treatment, control antibody, or
      anti-Nogo-A antibody (11C7). Animals were tested weekly after stroke surgery and
      daily after antibody treatment until the end of the study. Biotin dextran amine
      tracing was injected into the nonlesioned forelimb motor cortex at the end of
      behavioral testing to determine axonal plasticity. RESULTS: all rats showed
      similar forelimb impairment before treatment. Animals treated with anti-Nogo-A
      immunotherapy started to show improvement 3 weeks after treatment. Such
      improvement became significantly better than stroke-only control and control Ab
      treated animals, and persisted to the end of the study. Biotin dextran amine
      labeled axonal fiber analysis also showed significant enhanced corticorubral
      axonal sprouting from the contralesional forelimb motor cortex to the
      deafferented red nucleus in the anti-Nogo-A immunotherapy rats. CONCLUSIONS:
      these results indicate that improvement of chronic neurological deficits and
      enhancement of neuronal plasticity can be induced in the adult rat with anti-Nogo
      A immunotherapy, and that this therapy may be used to restore function even when
      administered long after ischemic brain damage has occurred.

PMID- 21088246
TI  - Prevalence of coronary atherosclerosis in patients with cerebral infarction.
AB  - BACKGROUND AND PURPOSE: there is an overlap between stroke and coronary heart
      disease, but the exact prevalence of coronary artery disease in patients with
      nonfatal cerebral infarction is unclear, particularly when there is no known
      history of coronary heart disease. METHODS: we consecutively enrolled 405
      patients presenting with acute cerebral infarction documented by neuroimaging who
      underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound
      examinations. Of the 342 patients with no known coronary heart disease, 315
      underwent coronary angiography a median of 8 days (interquartile range, 6-11)
      after stroke onset. RESULTS: coronary plaques on angiography, regardless of
      stenosis severity, were present in 61.9% of patients (95% confidence interval
      [CI], 56.5-67.3) and coronary stenoses >= 50% were found in 25.7% (95% CI, 20.9
      30.5). The overall prevalence of coronary plaque increased with the number of
      arterial territories (carotid or femoral arteries) involved, with an adjusted
      odds ratio of coronary artery disease of 1.25 (95% CI, 0.58-2.71) for presence of
      plaque in 1 territory, and 4.31 (95% CI, 1.92-9.68) for presence of plaque in
      both territories, compared with no plaque in either territory. The presence of
      plaque in both femoral and carotid arteries had an age- and sex-adjusted positive
      predictive value of 84% for presence of coronary plaque and a negative predictive
      value of 44%. CONCLUSIONS: there is a high burden of silent coronary artery
      disease in patients with nonfatal cerebral infarction and no known coronary heart
      disease, even in the absence of systemic atherosclerosis. The prevalence is even
      higher in patients with evidence of carotid and/or femoral plaque.

PMID- 21088245
TI  - Accuracy of susceptibility-weighted imaging for the detection of arteriovenous
      shunting in vascular malformations of the brain.
AB  - BACKGROUND AND PURPOSE: to determine the accuracy of susceptibility-weighted MRI
      (SWI) for the detection of arteriovenous shunting (AVS) in vascular malformations
      of the brain (BVM). METHODS: we retrospectively identified 60 patients who had
      been evaluated for known or suspected BVM by both SWI and digital subtraction
      angiography, without intervening treatment, during a 3-year period. SWI images
      were retrospectively assessed by 2 independent reviewers for the presence of AVS
      as determined by the presence of signal hyperintensity within a venous structure
      in the vicinity of the BVM. Discrepancies were resolved by consensus among a
      panel of 3 neuroradiologists. Accuracy parameters of SWI for the detection of AVS
      were calculated using digital subtraction angiography as the reference standard.
      RESULTS: a total of 80 BVM were identified in the 60 patients included in our
      study. Of the 29 BVM with AVS on digital subtraction angiography, 14 were
      untreated arteriovenous malformations, 10 were previously treated arteriovenous
      malformations, and 5 were untreated dural arteriovenous fistulas. Overall, SWI
      was 93% sensitive and 98% specific for the detection of AVS in BVM, with
      excellent interobserver agreement (kappa=0.94). In the 14 previously treated
      arteriovenous malformations, SWI was 100% sensitive and specific for the
      detection of AVS. In the 28 BVM associated with intracerebral hemorrhage, SWI was
      100% sensitive and 96% specific for the detection of AVS. CONCLUSIONS: SWI is
      accurate for the detection of arteriovenous shunting in vascular malformations of
      the brain and, for some patients, SWI may offer a noninvasive alternative to
      angiography in screening for or follow-up of treated BVM.

PMID- 21088247
TI  - N-substituted benztropine analogs: selective dopamine transporter ligands with a
      fast onset of action and minimal cocaine-like behavioral effects.
AB  - Previous studies suggested that differences between the behavioral effects of
      cocaine and analogs of benztropine were related to the relatively slow onset of
      action of the latter compounds. Several N-substituted benztropine analogs with a
      relatively fast onset of effects were studied to assess whether a fast onset of
      effects would render the effects more similar to those of cocaine. Only one of
      the compounds increased locomotor activity, and the increases were modest
      compared with those of 10 to 20 mg/kg cocaine. In rats trained to discriminate 10
      mg/kg cocaine from saline none of the compounds produced more than 40% cocaine
      like responds up to 2 h after injection. None of the compounds produced place
      conditioning when examined up to 90 min after injection, indicating minimal abuse
      liability. The compounds had 5.6 to 30 nM affinities at the dopamine transporter
      (DAT), with uniformly lower affinities at norepinephrine and serotonin
      transporters (from 490-4600 and 1420-7350 nM, respectively). Affinities at
      muscarinic M(1) receptors were from 100- to 300-fold lower than DAT affinities,
      suggesting minimal contribution of those sites to the behavioral effects of the
      compounds. Affinities at histaminic H(1) sites were from 11- to 43-fold lower
      than those for the DAT. The compounds also had affinity for sigma, 5
      hydroxytryptamine(1) (5-HT(1)), and 5-HT(2) receptors that may have contributed
      to their behavioral effects. Together, the results indicate that a slow onset of
      action is not a necessary condition for reduced cocaine-like effects of atypical
      DAT ligands and suggest several mechanisms that may contribute to the reduced
      cocaine-like efficacy of these compounds.

PMID- 21088249
TI  - High-mobility group box protein 1 neutralization reduces development of diet
      induced atherosclerosis in apolipoprotein e-deficient mice.
AB  - OBJECTIVE: High-mobility group box protein 1 (HMGB1) is a DNA-binding protein and
      cytokine highly expressed in atherosclerotic lesions, but its pathophysiological
      role in atherosclerosis is unknown. We investigated its role in the development
      of atherosclerosis in ApoE-/- mice. METHODS AND RESULTS: Apolipoprotein E
      deficient (ApoE-/-) mice fed a high-fat diet were administered a monoclonal anti
      HMGB1 neutralizing antibody, and the effects on lesion size, immune cell
      accumulation, and proinflammatory mediators were assessed using Oil Red O,
      immunohistochemistry, and real-time polymerase chain reaction. As with human
      atherosclerotic lesions, lesions in ApoE-/- mice expressed HMGB1. Treatment with
      the neutralizing antibody attenuated atherosclerosis by 55%. Macrophage
      accumulation was reduced by 43%, and vascular cell adhesion molecule-1 and
      monocyte chemoattractant protein-1 expression was attenuated by 48% and 72%,
      respectively. CD11c+ dendritic cells were reduced by 65%, and the mature (CD83+)
      population was reduced by 60%. Treatment also reduced CD4+ cells by nearly 50%.
      mRNAs in lesions encoding tumor necrosis factor-alpha and interleukin-1beta
      tended to be reduced. Mechanistically, HMGB1 stimulated macrophage migration in
      vitro and in vivo; in vivo, it markedly augmented the accumulation of F4/80+Gr
      1(Ly-6C)+ macrophages and also increased F4/80+CD11b+ macrophage numbers.
      CONCLUSIONS: HMGB1 exerts proatherogenic effects augmenting lesion development by
      stimulating macrophage migration, modulating proinflammatory mediators, and
      encouraging the accumulation of immune and smooth muscle cells.

PMID- 21088248
TI  - Vascular smooth muscle cell peroxisome proliferator-activated receptor-gamma
      mediates pioglitazone-reduced vascular lesion formation.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been
      reported to decrease vascular lesion formation. However, the critical role of
      vascular smooth muscle cell (VSMC) PPARgamma in vascular lesion formation
      following transplantation is not well understood. In this study, we investigated
      the role of VSMC PPARgamma-mediated signaling in transplantation-associated
      vascular lesion formation. METHODS AND RESULTS: Carotid arteries from smooth
      muscle cell-selective PPARgamma knockout (SMPG KO) and wild-type mice were
      transplanted to CBA/CaJ recipient mice. The recipient mice received a control
      diet or pioglitazone-containing diet. Pioglitazone reduced vascular lesion
      formation in transplanted wild-type, but not in SMPG KO carotid arteries.
      Histological analysis suggested that PPARgamma attenuates vascular lesion
      formation through antiinflammatory signaling, as evidenced by the increase of
      intimal inflammatory cells and tumor necrosis factor-alpha expression in SMPG KO
      allografts. Intravital microscopy revealed increased inflammatory cell rolling
      and attachment to endothelial cells in small blood vessels of SMPG KO mice
      following cytokine stimulation. SMPG KO mice, as shown by Western blotting, have
      elevated vascular cell adhesion molecule-1 (VCAM-1) expression. Furthermore,
      immunohistochemistry demonstrated SMPG KO allografts have increased VCAM-1.
      CONCLUSIONS: Loss of PPARgamma in VSMC promotes transplantation-associated
      vascular lesion formation through increased VCAM-1 expression. VSMC PPARgamma
      also mediates pioglitazone-reduced vascular lesion formation.

PMID- 21088250
TI  - Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II
      induced abdominal aortic aneurysm formation.
AB  - OBJECTIVE: Abdominal aortic aneurysms (AAA) are an age-related vascular disease
      and an important cause of morbidity and mortality. In this study, we sought to
      determine whether the catalytic component of telomerase, telomerase reverse
      transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation.
      METHODS AND RESULTS: Low-density lipoprotein receptor-deficient (LDLr-/-) mice
      were lethally irradiated and reconstituted with bone marrow-derived cells from
      TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a
      diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of
      Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived
      cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice
      revealed modest telomere attrition in circulating leukocytes at the study end
      point without any overt effect of the donor genotype on white blood cell counts.
      In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2
      (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased
      expression and activity of MMP-2 in response to stimulation with Ang II. Finally,
      we demonstrated in transient transfection studies that TERT overexpression
      activates the MMP-2 promoter in macrophages. CONCLUSIONS: TERT deficiency in bone
      marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/-
      mice and decreases MMP-2 expression. These results point to a previously
      unrecognized role of TERT in the pathogenesis of AAA.

PMID- 21088251
TI  - Deletion of EP4 on bone marrow-derived cells enhances inflammation and
      angiotensin II-induced abdominal aortic aneurysm formation.
AB  - OBJECTIVE: To examine whether a lack of prostaglandin E receptor 4 (EP4) on bone
      marrow-derived cells would increase local inflammation and enhance the formation
      of abdominal aortic aneurysm (AAA) in vivo. METHODS AND RESULTS: Prostaglandin
      E(2) (PGE(2)) through activation of EP4, can mute inflammation.
      Hypercholesterolemic low-density lipoprotein receptor knockout (LDLR(-/-)) mice
      transplanted with either EP4(+/+) (EP4(+/+)/LDLR(-/-)) or EP4(-/-) (EP4(-/
      )/LDLR(-/-)) bone marrow received infusions of angiotensin II to induce AAA.
      Deficiency of EP4 on bone marrow-derived cells increased the incidence (50% of
      male EP4(+/+)/LDLR(-/-) mice versus 88.9% of male EP4(-/-)/LDLR(-/-) mice
      developed AAA; and 22% of female EP4(+/+)/LDLR(-/-) mice versus 83.3% of female
      EP4(-/-)/LDLR(-/-) mice developed AAA) and severity of AAA, increased monocyte
      chemoattractant protein-1 (2.72-fold in males and 1.64-fold in females), and
      enhanced infiltration of macrophages (3.8-fold in males and 2.44-fold in females)
      and T cells (1.88-fold in males and 1.66-fold in females) into AAA lesions. Lack
      of EP4 on bone marrow-derived cells augmented elastin fragmentation, increased
      apoptotic markers, and decreased smooth muscle cell accumulation within AAA
      lesions. CONCLUSIONS: Deficiency of EP4 on bone marrow-derived cells boosted
      inflammation and AAA formation induced by angiotensin II in hyperlipidemic mice.
      This study affirms the pathophysiologic importance of PGE(2) signaling through
      EP4 as an endogenous anti-inflammatory pathway involved in experimental aneurysm
      formation.

PMID- 21088252
TI  - Flavopiridol protects against inflammation by attenuating leukocyte-endothelial
      interaction via inhibition of cyclin-dependent kinase 9.
AB  - OBJECTIVE: The cyclin-dependent kinase (CDK) inhibitor flavopiridol is currently
      being tested in clinical trials as anticancer drug. Beyond its cell death
      inducing action, we hypothesized that flavopiridol affects inflammatory
      processes. Therefore, we elucidated the action of flavopiridol on leukocyte
      endothelial cell interaction and endothelial activation in vivo and in vitro and
      studied the underlying molecular mechanisms. METHODS AND RESULTS: Flavopiridol
      suppressed concanavalin A-induced hepatitis and neutrophil infiltration into
      liver tissue. Flavopiridol also inhibited tumor necrosis factor-alpha-induced
      leukocyte-endothelial cell interaction in the mouse cremaster muscle. Endothelial
      cells were found to be the major target of flavopiridol, which blocked the
      expression of endothelial cell adhesion molecules (intercellular adhesion
      molecule-1, vascular cell adhesion molecule-1, and E-selectin), as well as NF
      kappaB-dependent transcription. Flavopiridol did not affect inhibitor of kappaB
      (IkappaB) kinase, the degradation and phosphorylation of IkappaBalpha, nuclear
      translocation of p65, or nuclear factor-kappaB (NF-kappaB) DNA-binding activity.
      By performing a cellular kinome array and a kinase activity panel, we found LIM
      domain kinase-1 (LIMK1), casein kinase 2, c-Jun N-terminal kinase (JNK), protein
      kinase C (PKC), CDK4, CDK6, CDK8, and CDK9 to be influenced by flavopiridol.
      Using specific inhibitors, as well as RNA interference (RNAi), we revealed that
      only CDK9 is responsible for the action of flavopiridol. CONCLUSIONS: Our study
      highlights flavopiridol as a promising antiinflammatory compound and inhibition
      of CDK9 as a novel approach for the treatment of inflammation-associated
      diseases.

PMID- 21088254
TI  - Tumor suppressor CHK2: regulator of DNA damage response and mediator of
      chromosomal stability.
AB  - CHK2 is a multiorgan tumor susceptibility gene that encodes for a
      serine/threonine protein kinase involved in the response to cellular DNA damage.
      After ATM-mediated phosphorylation, the activated Chk2 kinase can act as a signal
      transducer and phosphorylate a variety of substrates, including the Cdc25
      phosphatases, p53, PML, E2F-1, and Brca1, which has been associated with halting
      the cell cycle, the initiation of DNA repair, and the induction of apoptosis
      after DNA damage. In addition, recent work has revealed another, DNA-damage
      independent function of Chk2 during mitosis that is required for proper mitotic
      spindle assembly and maintenance of chromosomal stability. This novel role
      involves a mitotic phosphorylation of the tumor suppressor Brca1 by the Chk2
      kinase. On the basis of its role during DNA damage response, Chk2 has been
      suggested as an anticancer therapy target, but given its recently discovered new
      function and its role as a tumor suppressor, it is questionable whether
      inhibition of Chk2 is indeed beneficial for anticancer treatment. However,
      investigators may be able to exploit the loss of CHK2 in human tumors to develop
      novel therapies based on synthetic lethal interactions.

PMID- 21088253
TI  - The bilirubin-increasing drug atazanavir improves endothelial function in
      patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: In type 2 diabetes mellitus (T2DM), oxidative stress gives rise to
      endothelial dysfunction. Bilirubin, a powerful endogenous antioxidant,
      significantly attenuates endothelial dysfunction in preclinical experiments. The
      Gilbert syndrome is accompanied by a mild and lifelong hyperbilirubinemia and
      associated with only one third of the usual cardiovascular mortality risk. The
      hyperbilirubinemia caused by atazanavir treatment closely resembles the Gilbert
      syndrome. We thus hypothesized that treatment with atazanavir would ameliorate
      oxidative stress and vascular inflammation and improve endothelial function in
      T2DM. METHODS AND RESULTS: In a double-blind, placebo-controlled crossover
      design, we induced a moderate hyperbilirubinemia by a 3-day atazanavir treatment
      in 16 subjects experiencing T2DM. On the fourth day, endothelial function was
      assessed by venous occlusion plethysmography. Endothelium-dependent and
      endothelium-independent vasodilation were assessed by intraarterial infusion of
      acetylcholine and nitroglycerin, respectively. Atazanavir treatment induced an
      increase in average bilirubin levels from 7 MUmol/L (0.4 mg/dL) to 64 MUmol/L
      (3.8 mg/dL). A significant improvement in plasma antioxidant capacity (P<0.001)
      and endothelium-dependent vasodilation (P=0.036) and a decrease in plasma von
      Willebrand factor (P=0.052) were observed. CONCLUSIONS: Experimental
      hyperbilirubinemia is associated with a significant improvement of endothelial
      function in T2DM.

PMID- 21088255
TI  - Fine-needle aspiration biopsies for gene expression ratio-based diagnostic and
      prognostic tests in malignant pleural mesothelioma.
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive disease associated
      with median survival between 9 and 12 months. The correct diagnosis of MPM is
      sometimes challenging and usually requires solid tissue biopsies rather than fine
      needle aspiration biopsies (FNA). We postulated that the accuracy of FNA-based
      diagnosis might be improved by the addition of molecular tests using a gene
      expression ratio-based algorithm and that prognostic tests could be similarly
      performed. EXPERIMENTAL DESIGN: Two MPM and 2 lung cancer cell lines were used to
      establish the minimal quantity of RNA required to perform the gene ratio test. On
      the basis of these results, 276 ex vivo FNA biopsies from 63 MPM patients and 250
      ex vivo FNA samples from 92 lung cancer patients were analyzed using previously
      described diagnostic and prognostic tests based on gene expression ratios.
      RESULTS: We found that the sensitivity of the diagnostic test for MPM was 100%
      [95% confidence interval (CI): 95%-100%] and the specificity in primary lung
      adenocarcinoma was 90% (95% CI: 81%-95%). The FNA-based prognostic classification
      was concordant among 76% (95% CI: 65%-87%) of patients with the risk assignment
      in a subset of the matched surgical specimens previously analyzed by the
      prognostic test. CONCLUSIONS: Sufficient RNA can be extracted from most FNA
      biopsies to perform gene expression molecular tests. In particular, we show that
      the gene expression ratio algorithms performed well when applied to diagnosis and
      prognosis in MPM. This study provides support for the development of additional
      RNA molecular tests that may enhance the utility of FNA in the management of
      other solid cancers.

PMID- 21088256
TI  - beta-catenin activation is associated with specific clinical and pathologic
      characteristics and a poor outcome in adrenocortical carcinoma.
AB  - PURPOSE: Activation of the Wnt/beta-catenin signaling pathway is frequent in
      adrenocortical carcinoma (ACC) and might be associated with a more aggressive
      phenotype. The objective of this study was to assess the prognostic value of beta
      catenin immunohistochemistry and CTNNB1 (beta-catenin gene)/APC (adenomatous
      polyposis coli gene) mutations in patients with resected primary ACC.
      EXPERIMENTAL DESIGN: In 79 patients with resected primary ACC from a French
      cohort (Cochin-COMETE), beta-catenin expression was assessed on tumor specimens
      by immunohistochemistry. For patients with available DNA (n = 49), CTNNB1, and
      APC hotspot (mutation cluster region), were sequenced. Association between these
      results and the clinicopathologic characteristics of the ACC and overall and
      disease-free survival were studied. Results were confirmed on a tissue microarray
      from an independent multicentric cohort of 92 ACC from Germany (German-ENSAT
      cohort). RESULTS: In the Cochin-COMETE cohort, the presence of a beta-catenin
      nuclear staining was significantly associated with a higher ENSAT tumor stage
      (i.e., stages III and IV), higher Weiss score, more frequent necrosis, mitoses,
      and CTNNB1/APC mutations. beta-Catenin nuclear staining and the presence of
      CTNNB1/APC mutations were both associated with decreased overall and disease-free
      survival, and were independent predictive factors of survival in multivariate
      analysis. The same results were observed in the German-ENSAT cohort. CONCLUSIONS:
      Wnt/beta-catenin activation, confirmed by the presence of beta-catenin nuclear
      staining, is an independent prognostic factor of overall and disease-free
      survival in patients with resected primary ACC.

PMID- 21088257
TI  - Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS
      penetration and intracellular accumulation.
AB  - PURPOSE: To study the role of drug transporters in central nervous system (CNS)
      penetration and cellular accumulation of erlotinib and its metabolite, OSI-420.
      EXPERIMENTAL DESIGN: After oral erlotinib administration to wild-type and ATP
      binding cassette (ABC) transporter-knockout mice (Mdr1a/b(-/-), Abcg2(-/-),
      Mdr1a/b(-/-)Abcg2(-/-), and Abcc4(-/-)), plasma was collected and brain
      extracellular fluid (ECF) was sampled using intracerebral microdialysis. A
      pharmacokinetic model was fit to erlotinib and OSI-420 concentration-time data,
      and brain penetration (P(Brain)) was estimated by the ratio of ECF-to-unbound
      plasma area under concentration-time curves. Intracellular accumulation of
      erlotinib was assessed in cells overexpressing human ABC transporters or SLC22A
      solute carriers. RESULTS: P(Brain) in wild-type mice was 0.27 +/- 0.11 and 0.07
      +/- 0.02 (mean +/- SD) for erlotinib and OSI-420, respectively. Erlotinib and OSI
      420 P(Brain) in Abcg2(-/-) and Mdr1a/b(-/-)Abcg2(-/-) mice were significantly
      higher than in wild-type mice. Mdr1a/b(-/-) mice showed similar brain ECF
      penetration as wild-type mice (0.49 +/- 0.37 and 0.04 +/- 0.02 for erlotinib and
      OSI-420, respectively). In vitro, erlotinib and OSI-420 accumulation was
      significantly lower in cells overexpressing breast cancer resistance protein
      (BCRP) than in control cells. Only OSI-420, not erlotinib, showed lower
      accumulation in cells overexpressing P-glycoprotein (P-gp) than in control cells.
      The P-gp/BCRP inhibitor elacridar increased erlotinib and OSI-420 accumulation in
      BCRP-overexpressing cells. Erlotinib uptake was higher in OAT3- and OCT2
      transfected cells than in empty vector control cells. CONCLUSION: Abcg2 is the
      main efflux transporter preventing erlotinib and OSI-420 penetration in mouse
      brain. Erlotinib and OSI-420 are substrates for SLC22A family members OAT3 and
      OCT2. Our findings provide a mechanistic basis for erlotinib CNS penetration,
      cellular uptake, and efflux mechanisms.

PMID- 21088259
TI  - MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to
      apoptosis induced by the RAF inhibitor PLX4720.
AB  - PURPOSE: To examine mechanisms that determine long-term responses of B-RAF(V600E)
      melanoma cells to B-RAF inhibitors. EXPERIMENTAL DESIGN: B-RAF(V600E) melanoma
      cells were exposed to the B-RAF inhibitor PLX4720 for prolonged periods to select
      for cells resistant to apoptosis induced by the inhibitor. The resultant cells
      were analyzed for activation of extracellular signal regulated kinase (ERK),
      MAP/ERK kinase (MEK), and Akt, and related signals. Their roles in survival of
      the cells were also examined. RESULTS: B-RAF(V600E) melanoma cells selected for
      resistant to PLX4720-induced apoptosis retained the V600E mutation in B-RAF, and
      proliferated steadily in the presence of the inhibitor, albeit with slow growth
      rate. These cells displayed high levels of ERK activation, that is, at least in
      part, independent of the conventional RAF/MEK/ERK pathway, as MEK activation was
      low and inhibition of MEK did not significantly block activation of ERK. In
      contrast, extracellular signals appeared involved. This was associated with
      elevated activation of the phosphoinositide 3-kinase (PI3k)/Akt pathway and could
      be inhibited by serum starvation and inhibition of PI3k/Akt. Inhibition of MEK
      did not impact on survival of these cells, whereas serum starvation, inhibition
      of PI3K/Akt, and inhibition of ERK1/2 reduced their viability. CONCLUSIONS: These
      results indicate that sensitivity to induction of apoptosis may be a major
      determinant of long-term responses of B-RAF(V600E) melanomas to specific
      inhibitors and suggest that rebound melanoma growth after initial treatment with
      the inhibitors may not be responsive to MEK inhibitors, but may be susceptible to
      inhibition of the PI3k/Akt pathway.

PMID- 21088258
TI  - Carbon nanotubes enhance CpG uptake and potentiate antiglioma immunity.
AB  - PURPOSE: Stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides
      (CpG) has been shown to counteract the immunosuppressive microenvironment and to
      inhibit tumor growth in glioma models. Because TLR9 is located intracellularly,
      we hypothesized that methods that enhance its internalization may also potentiate
      its immunostimulatory response. The goal of this study was to evaluate carbon
      nanotubes (CNT) as a CpG delivery vehicle in brain tumor models. EXPERIMENTAL
      DESIGN: Functionalized single-walled CNTs were conjugated with CpG (CNT-CpG) and
      evaluated in vitro and in mice bearing intracranial GL261 gliomas. Flow cytometry
      was used to assess CNT-CpG uptake and antiglioma immune response. Tumor growth
      was measured by bioluminescent imaging, histology, and animal survival. RESULTS:
      CNT-CpG was nontoxic and enhanced CpG uptake both in vitro and intracranial
      gliomas. CNT-mediated CpG delivery also potentiated proinflammatory cytokine
      production by primary monocytes. Interestingly, a single intracranial injection
      of low-dose CNT-CpG (but not free CpG or blank CNT) eradicated intracranial GL261
      gliomas in half of tumor-bearing mice. Moreover, surviving animals exhibited
      durable tumor-free remission (>3 months), and were protected from intracranial
      tumor rechallenge, demonstrating induction of long-term antitumor immunity.
      CONCLUSIONS: These findings suggest that CNTs can potentiate CpG immunopotency by
      enhancing its delivery into tumor-associated inflammatory cells.

PMID- 21088260
TI  - Dynamic treatment regimes for managing chronic health conditions: a statistical
      perspective.
AB  - Dynamic treatment regimes are an emerging and important methodological area in
      health research, particularly in the management of chronic health conditions.
      This paradigm encompasses the ideological shift in research from the acute care
      model to the chronic care model. It allows individualization of treatment (type,
      dosage, timing) at each stage of intervention. Constructing evidence-based
      dynamic treatment regimes requires implementation of cutting-edge design and
      analysis tools. Here I briefly discuss some of these modern tools, namely the
      sequential multiple assignment randomized trial (SMART) design and a regression
      based analysis approach called Q-learning.

PMID- 21088262
TI  - Associations of workplace aggression with work-related well-being among nurses in
      the Philippines.
AB  - OBJECTIVES: We examined whether workplace aggression was associated with self
      rated health and work-related injury and illness among nurses in the Philippines.
      METHODS: Our data came from a cross-sectional survey of nurses (n = 687) in the
      Philippines. We assessed the associations of self-reported physical assault and
      verbal abuse with self-rated health, work-related injury and illness, and missed
      workdays with Poisson regression. Control variables included demographic and work
      characteristics (e.g., hours worked, work setting, shift). RESULTS: Verbal abuse
      was associated with poor general health (prevalence ratio [PR] = 1.94; 95%
      confidence interval [CI] = 1.09, 3.45). Both physical assault and verbal abuse
      were associated with work-related injury (PR = 1.48; 95% CI = 1.00, 2.20; PR =
      1.72; 95% CI = 1.34, 2.23, respectively) and work-related illness (PR = 1.46; 95%
      CI = 0.99, 2.15; PR = 1.68; 95% CI = 1.32, 2.14, respectively) after demographic
      and work characteristics were accounted for in the model. In addition, physical
      assault was associated with missed workdays (PR = 1.56; 95% CI = 1.02, 2.33).
      CONCLUSIONS: Workplace aggression was associated with increased risks of poor
      general health and adverse work-related health outcomes among nurses in the
      Philippines.

PMID- 21088261
TI  - Timing of first dental visits for newly Medicaid-enrolled children with an
      intellectual or developmental disability in Iowa, 2005-2007.
AB  - OBJECTIVES: We evaluated the relationship between having an intellectual or
      developmental disability (IDD) and the timing of the first dental visit for
      children who were newly enrolled in Medicaid in Iowa. METHODS: We identified
      children aged 3 to 8 years with and without IDD who were newly enrolled in the
      Iowa Medicaid program in 2005 (N = 5391). We gathered data on presence of IDD,
      health status, age at baseline, gender, length of Medicaid enrollment, medical
      care visits, household Medicaid enrollment, urbanization, residence in a
      federally designated Health Professional Shortage Area (HPSA), and time of first
      dental visit through 2007. RESULTS: About 32% of children had a first dental
      visit within 6 months of enrollment; this proportion increased to 49%, 64%, and
      74% by years 1, 2, and 3, respectively. In the unadjusted models, there was no
      significant difference between children with and without IDD in time to first
      dental visit (P = .22). After adjusting for model covariates, however, children
      with IDD were 31% more likely to have a delayed first dental visit (P = .04).
      CONCLUSIONS: Newly Medicaid-enrolled children aged 3 to 8 years with IDD in Iowa
      were significantly more likely to have a later first dental visit. Future
      interventions should focus on ensuring timely access to first dental visits for
      all Medicaid-enrolled children, with an emphasis on those with IDD.

PMID- 21088263
TI  - The neighborhood food environment and adult weight status: estimates from
      longitudinal data.
AB  - OBJECTIVES: I used longitudinal data to consider the relationship between the
      neighborhood food environment and adult weight status. METHODS: I combined
      individual-level data on adults from the 1998 through 2004 survey years of the
      National Longitudinal Survey of Youth 1979 with zip code-level data on the
      neighborhood food environment. I estimated ordinary least squares models of
      obesity, body mass index (BMI), and change in BMI. RESULTS: For residents of
      urban areas, the neighborhood density of small grocery stores was positively and
      significantly related to obesity and BMI. For individuals who moved from a rural
      area to an urban area over a 2-year period, changes in neighborhood supermarket
      density, small grocery store density, and full-service restaurant density were
      significantly related to the change in BMI over that period. CONCLUSIONS:
      Residents of urban neighborhoods with a higher concentration of small grocery
      stores may be more likely to patronize these stores and consume more calories
      because small grocery stores tend to offer more unhealthy food options than
      healthy food options. Moving to an urban area may expose movers to a wider
      variety of food options that may influence calorie consumption.

PMID- 21088264
TI  - The differential association between education and infant mortality by nativity
      status of Chinese American mothers: a life-course perspective.
AB  - OBJECTIVES: Integrating evidence from demography and epidemiology, we
      investigated whether the association between maternal achieved status (education)
      and infant mortality differed by maternal place of origin (nativity) over the
      life course of Chinese Americans. METHODS: We conducted a population-based cohort
      study of singleton live births to US-resident Chinese American mothers using
      National Center for Health Statistics 1995 to 2000 linked live birth and infant
      death cohort files. We categorized mothers by nativity (US born [n = 15 040] or
      foreign born [n = 150 620]) and education (>= 16 years, 13-15 years, or <= 12
      years), forming 6 life-course trajectories. We performed Cox proportional hazards
      regressions of infant mortality. RESULTS: We found significant nativity-by
      education interaction via stratified analyses and testing interaction terms (P <
      .03) and substantial differentials in infant mortality across divergent maternal
      life-course trajectories. Low education was more detrimental for the US born,
      with the highest risk among US-born mothers with 12 years or less of education
      (adjusted hazard ratio = 2.39; 95% confidence interval = 1.33, 4.27).
      CONCLUSIONS: Maternal nativity and education synergistically affect infant
      mortality among Chinese Americans, suggesting the importance of searching for
      potential mechanisms over the maternal life course and targeting identified high
      risk groups and potential downward mobility.

PMID- 21088266
TI  - HIV risk among young African American men who have sex with men: a case-control
      study in Mississippi.
AB  - OBJECTIVES: We conducted a case-control study in the Jackson, Mississippi, area
      to identify factors associated with HIV infection among young African American
      men who have sex with men (MSM). METHODS: During February to April 2008, we used
      surveillance records to identify young (16-25 years old) African American MSM
      diagnosed with HIV between 2006 and 2008 (case participants) and recruited young
      African American MSM who did not have HIV (controls). Logistic regression
      analysis was used to assess factors associated with HIV infection. RESULTS: In a
      multivariable analysis of 25 case participants and 85 controls, having older male
      partners (adjusted odds ratio [OR] = 5.5; 95% confidence interval [CI] = 1.8,
      17.3), engaging in unprotected anal intercourse with casual male partners
      (adjusted OR = 6.3; 95% CI = 1.8, 22.3), and being likely to give in to a partner
      who wanted to have unprotected sex (adjusted OR = 5.0; 95% CI = 1.2, 20.6) were
      associated with HIV infection. CONCLUSIONS: Given the high prevalence of risk
      behaviors among the young African American MSM in our study, HIV prevention
      efforts must begin before or during early adolescence and need to focus on
      improving negotiation and communication regarding sex.

PMID- 21088265
TI  - An examination of periodontal treatment, dental care, and pregnancy outcomes in
      an insured population in the United States.
AB  - OBJECTIVES: We examined whether periodontal treatment or other dental care is
      associated with adverse birth outcomes within a medical and dental insurance
      database. METHODS: In a retrospective cohort study, we examined the records of
      23,441 women enrolled in a national insurance plan who delivered live births from
      singleton pregnancies in the United States between January 1, 2003, and September
      30, 2006, for adverse birth outcomes on the basis of dental treatment received.
      We compared rates of low birthweight and preterm birth among 5 groups, specifying
      the relative timing and type of dental treatment received. We used logistic
      regression analysis to compare outcome rates across treatment groups while
      adjusting for duration of continuous dental coverage, maternal age, pregnancy
      complications, neighborhood-level income, and race/ethnicity. RESULTS: Analyses
      showed that women who received preventive dental care had better birth outcomes
      than did those who received no treatment (P < .001). We observed no evidence of
      increased odds of adverse birth outcomes from dental or periodontal treatment.
      CONCLUSIONS: For women with medical and dental insurance, preventive care is
      associated with a lower incidence of adverse birth outcomes.

PMID- 21088268
TI  - Blood lead levels of refugee children resettled in Massachusetts, 2000 to 2007.
AB  - OBJECTIVES: We described elevated blood lead level (BLL; >= 10 MUg/dL) prevalence
      among newly arrived refugee children in Massachusetts. We also investigated the
      incidence of BLL increases and BLLs newly elevated to 20 MUg/dL or higher in the
      year following initial testing, along with associated factors. METHODS: We merged
      data from the Massachusetts Department of Public Health's Refugee and Immigrant
      Health Program and the Childhood Lead Poisoning Prevention Program on 1148
      refugee children younger than 7 years who arrived in Massachusetts from 2000 to
      2007. RESULTS: Elevated BLL prevalence was 16% among newly arrived refugee
      children. The rate ratio for BLL elevation to 20 MUg/dL or higher after arrival
      was 12.3 (95% confidence interval [CI] = 6.2, 24.5) compared with children in
      communities the state defines as high-risk for childhood lead exposure. Residence
      in a census tract with older housing (median year built before 1950) was
      associated with a higher rate of BLL increases after resettlement (hazard ratio =
      1.7; 95% CI = 1.2, 2.3). CONCLUSIONS: Refugee children are at high risk of lead
      exposure before and after resettlement in Massachusetts. A national surveillance
      system of refugee children's BLLs following resettlement would allow more in
      depth analysis.

PMID- 21088267
TI  - Spatial access to syringe exchange programs and pharmacies selling over-the
      counter syringes as predictors of drug injectors' use of sterile syringes.
AB  - OBJECTIVES: We examined relationships of spatial access to syringe exchange
      programs (SEPs) and pharmacies selling over-the-counter (OTC) syringes with New
      York City drug injectors' harm reduction practices. METHODS: Each year from 1995
      to 2006, we measured the percentage of 42 city health districts' surface area
      that was within 1 mile of an SEP or OTC pharmacy. We applied hierarchical
      generalized linear models to investigate relationships between these exposures
      and the odds that injectors (n = 4003) used a sterile syringe for at least 75% of
      injections in the past 6 months. RESULTS: A 1-unit increase in the natural log of
      the percentage of a district's surface area within a mile of an SEP in 1995 was
      associated with a 26% increase in the odds of injecting with a sterile syringe; a
      1-unit increase in this exposure over time increased these odds 23%. A 1-unit
      increase in the natural log of OTC pharmacy access improved these odds 15%.
      CONCLUSIONS: Greater spatial access to SEPs and OTC pharmacies improved
      injectors' capacity to engage in harm reduction practices that reduce HIV and HCV
      transmission.

PMID- 21088269
TI  - Should we end military recruiting in high schools as a matter of child protection
      and public health?
AB  - Recruiters for the various US armed forces have free access to our nation's high
      schools, as mandated by the No Child Left Behind Act. Military recruiter
      behaviors are disturbingly similar to predatory grooming. Adults in the active
      military service are reported to experience increased mental health risks,
      including stress, substance abuse, and suicide, and the youngest soldiers
      consistently show the worst health effects, suggesting military service is
      associated with disproportionately poor health for this population. We describe
      the actions of a high school parent teacher student association in Seattle,
      Washington, which sought to limit the aggressive recruitment of children younger
      than 18 years into the military.

PMID- 21088270
TI  - Potential national and state medical care savings from primary disease
      prevention.
AB  - OBJECTIVES: We estimated national and state-level potential medical care cost
      savings achievable through modest reductions in the prevalence of several
      diseases associated with the same lifestyle-related risk factors. METHODS: Using
      Medical Expenditure Panel Survey Household Component data (2003-2005), we
      estimated the effects on medical spending over time of reductions in the
      prevalence of diabetes, hypertension, and related conditions amenable to primary
      prevention by comparing simulated counterfactual morbidity and medical care
      expenditures to actual disease and expenditure patterns. We produced state-level
      estimates of spending by using multivariate reweighting techniques. RESULTS:
      Nationally, we estimated that reducing diabetes and hypertension prevalence by 5%
      would save approximately $9 billion annually in the near term. With resulting
      reductions in comorbidities and selected related conditions, savings could rise
      to approximately $24.7 billion annually in the medium term. Returns were greatest
      in absolute terms for private payers, but greatest in percentage terms for public
      payers. State savings varied with demographic makeup and prevailing morbidity.
      CONCLUSIONS: Well-designed interventions that achieve improvements in lifestyle
      related risk factors could result in sufficient savings in the short and medium
      term to substantially offset intervention costs.

PMID- 21088272
TI  - Graphic-output temperature data loggers for monitoring vaccine refrigeration:
      implications for pertussis.
AB  - We conducted the first US study using graphic-output temperature data loggers in
      quantifying cold chain failure. Fifty-four vaccine refrigerators of a county
      outpatient health system were studied. Forty-eight percent maintained
      temperatures of 2 degrees C to 8 degrees C and 24% had protracted periods of
      temperatures less than 0 degrees C. The correlation between the percentage of
      refrigerators with freezing temperatures and the pertussis rate for each health
      region was r = 0.76. The findings suggest that improper vaccine storage may have
      contributed to recent increases in pertussis rates.

PMID- 21088271
TI  - Posttraumatic stress disorder and HIV risk among poor, inner-city women receiving
      care in an emergency department.
AB  - OBJECTIVES: We examined the associations between posttraumatic stress disorder
      (PTSD) and HIV risk behaviors among a random sample of 241 low-income women
      receiving care in an urban emergency department. METHODS: We recruited
      participants from the emergency department waiting room during randomly selected
      6-hour blocks of time. Multivariate analyses and propensity score weighting were
      used to examine the associations between PTSD and HIV risk after adjustment for
      potentially confounding sociodemographic variables, substance use, childhood
      sexual abuse, and intimate partner violence. RESULTS: A large majority of the
      sample self-identified as Latina (49%) or African American (44%). Almost one
      third (29%) of the participants met PTSD criteria. Women who exhibited symptoms
      in 1 or more PTSD symptom clusters were more likely than women who did not to
      report having had sex with multiple sexual partners, having had sex with a risky
      partner, and having experienced partner violence related to condom use in the
      preceding 6 months. CONCLUSIONS: The high rate of PTSD found in this sample and
      the significant associations between PTSD symptom clusters and partner-related
      risk behaviors highlight the need to take PTSD into account when designing HIV
      prevention interventions for low-income, urban women.

PMID- 21088274
TI  - Pleasing the masses: messages for daily life management in African American
      women's popular media sources.
AB  - OBJECTIVES: Using African American women's insights on their own health
      experiences, we explored how their daily life management was linked to the
      "strong Black woman" (SBW) script, and the health implications of that script.
      METHODS: Using the search term "strong Black woman," we identified 20 articles
      from African American women's magazines and 10 blog sites linked to the SBW
      script and analyzed their content. We created thematic categories (role
      management, coping, and self-care) and extracted issues relevant to African
      American women's health. RESULTS: Adherence to the SBW script was linked to
      women's daily life management and health experiences. Themes such as self
      sacrificial role management ("please the masses"), emotional suppression ("game
      face"), and postponement of self-care ("last on the list") incited internal
      distress and evinced negative health consequences. CONCLUSIONS: Scientists,
      activists, and health care professionals would be aided in forming initiatives
      aimed at reducing health disparities among African American women by heeding the
      insights on their health experiences that they express in popular media sources.

PMID- 21088273
TI  - A qualitative assessment of community-based breast health navigation services for
      Southeast Asian women in Southern California: recommendations for developing a
      navigator training curriculum.
AB  - OBJECTIVES: We identified key elements required for a training curriculum for
      Southeast Asian community-based health navigators (CBHNs), who help low-income,
      immigrant Cambodian, Laotian, Thai, and Vietnamese women negotiate cultural and
      systemic barriers to breast cancer screening and care in the United States.
      METHODS: We gathered the perspectives of 3 groups: CBHNs, community members, and
      their providers. We conducted 16 focus groups with 110 women representing
      different stages of the cancer care continuum and in-depth interviews with 15
      providers and 10 navigators to identify the essential roles, skills, and
      interpersonal qualities that characterize successful CBHNs. RESULTS: The most
      important areas identified for training CBHNs were information (e.g., knowing
      pertinent medical information and how to navigate resources), logistics
      (transportation, interpretation), and affective interpersonal skills
      (understanding the language and cultural beliefs of patients, communicating with
      providers, establishing trust). CONCLUSIONS: CBHNs serve a crucial role in
      building trust and making screening practices culturally meaningful, accessible,
      usable, and acceptable. Future research should focus on developing training
      curricula, policies, resources, and funding to better maximize the expertise and
      services that CBHNs provide and to expand our findings to other underserved
      communities.

PMID- 21088275
TI  - Nanotechnology takes a new look at old drugs.

PMID- 21088276
TI  - Oncologists want FDA to rethink REMS.

PMID- 21088278
TI  - Gene variants offer clues to high-risk childhood ALL.

PMID- 21088279
TI  - Re: Breast tissue composition and susceptibility to breast cancer.

PMID- 21088277
TI  - Effect of nitroxoline on angiogenesis and growth of human bladder cancer.
AB  - BACKGROUND: Angiogenesis plays an important role in tumor growth and metastasis;
      therefore, inhibition of angiogenesis is a promising strategy for developing new
      anticancer drugs. Type 2 methionine aminopeptidase (MetAP2) protein is likely a
      molecular target of angiogenesis inhibitors. METHODS: Nitroxoline, an antibiotic
      used to treat urinary tract infections, was identified from a high-throughput
      screen of a library of 175,000 compounds for MetAP2 inhibitors and from a
      parallel screen using the Johns Hopkins Drug Library to identify currently used
      clinical drugs that can also inhibit human umbilical vein endothelial cells
      (HUVEC) proliferation. To investigate the mechanism of action of nitroxoline,
      inhibition of MetAP2 activity and induction of senescence were assessed in HUVEC.
      To test the antiangiogenic activity of nitroxoline, endothelial tube formation in
      Matrigel and microvessel formation in Matrigel plugs in vivo were assessed.
      Antitumor efficacy of nitroxoline was evaluated in mouse models of human breast
      cancer xenograft (n = 10) and bladder cancer orthotopic xenograft (n = 11).
      Furthermore, the mechanism of action of nitroxoline was investigated in vivo.
      RESULTS: Nitroxoline inhibited MetAP2 activity in vitro (half maximal inhibitory
      concentration [IC(50)] = 54.8 nM, 95% confidence interval [CI] = 22.6 to 132.8
      nM) and HUVEC proliferation (IC(50) = 1.9 MUM, 95% CI = 1.54 to 2.39 MUM).
      Nitroxoline inhibited MetAP2 activity in HUVEC in a dose-dependent manner and
      induced premature senescence in a biphasic manner. Nitroxoline inhibited
      endothelial tube formation in Matrigel and reduced microvessel density in vivo.
      Mice (five per group) treated with nitroxoline showed a 60% reduction in tumor
      volume in breast cancer xenografts (tumor volume on day 30, vehicle vs
      nitroxoline, mean = 215.4 vs 86.5 mm(3), difference = 128.9 mm(3), 95% CI = 32.9
      to 225.0 mm(3), P = .012) and statistically significantly inhibited growth of
      bladder cancer in an orthotopic mouse model (tumor bioluminescence intensities of
      vehicle [n = 5] vs nitroxoline [n = 6], P = .045). CONCLUSION: Nitroxoline shows
      promise as a potential therapeutic antiangiogenic agent.

PMID- 21088280
TI  - NCI's clinical trial system: efficiencies grow, debate goes on.

PMID- 21088281
TI  - StatBite: Current ESA usage among cancer patients.

PMID- 21088283
TI  - Blood quantum and perceptions of black-white biracial targets: the black ancestry
      prototype model of affirmative action.
AB  - The present study examined the causal role of amount of Black ancestry in
      targets' perceived fit with Black prototypes and perceivers' categorization of
      biracial targets. Greater Black ancestry increased the likelihood that perceivers
      categorized biracial targets as Black and perceived targets as fitting Black
      prototypes (e.g., experiencing racial discrimination, possessing stereotypic
      traits). These results persisted, controlling for perceptions of phenotype that
      stem from ancestry information. Perceivers' beliefs about how society would
      categorize the biracial targets predicted perceptions of discrimination, whereas
      perceivers' beliefs about the targets' self-categorization predicted trait
      perceptions. The results of this study support the Black ancestry prototype model
      of affirmative action, which reveals the downstream consequences of Black
      ancestry for the distribution of minority resources (e.g., affirmative action) to
      biracial targets.

PMID- 21088282
TI  - Tissue-specific disallowance of housekeeping genes: the other face of cell
      differentiation.
AB  - We report on a hitherto poorly characterized class of genes that are expressed in
      all tissues, except in one. Often, these genes have been classified as
      housekeeping genes, based on their nearly ubiquitous expression. However, the
      specific repression in one tissue defines a special class of "disallowed genes."
      In this paper, we used the intersection-union test to screen for such genes in a
      multi-tissue panel of genome-wide mRNA expression data. We propose that
      disallowed genes need to be repressed in the specific target tissue to ensure
      correct tissue function. We provide mechanistic data of repression with two
      metabolic examples, exercise-induced inappropriate insulin release and
      interference with ketogenesis in liver. Developmentally, this repression is
      established during tissue maturation in the early postnatal period involving
      epigenetic changes in histone methylation. In addition, tissue-specific
      expression of microRNAs can further diminish these repressed mRNAs. Together, we
      provide a systematic analysis of tissue-specific repression of housekeeping
      genes, a phenomenon that has not been studied so far on a genome-wide basis and,
      when perturbed, can lead to human disease.

PMID- 21088284
TI  - Trends in Diseases Reported on US Death Certificates That Mentioned HIV
      Infection, 1996-2006.
AB  - OBJECTIVE: We examined trends during 1996-2006 in diseases reported on death
      certificates that mentioned HIV infection. METHODS: We analyzed multiple-cause
      mortality data compiled from all US death certificates with any mention of HIV to
      determine the annual percentages of deaths with various diseases. RESULTS: Deaths
      reported with HIV during 1996-2006 decreased from 35 340 to 13 750. Standardized
      percentages of death certificates reporting AIDS-defining opportunistic
      infections also decreased: pneumocytosis (6.3% to 5.1%), nontuberculous
      mycobacteriosis (5.5% to 1.8%), cytomegalovirus (5.7% to 1.2%). Non-Hodgkin's
      lymphoma rose from 4.8% in 1996 to 6.4% in 1997 and declined to 5.0% in 2001,
      while Kaposi's sarcoma declined from 3.7% in 1996 to 1.7% in 2001; these AIDS
      defining cancers had stable percentages after 2001. All other cancers increased
      during 1996-2006 (2.7% to 7.3%). The percentage of deaths with diseases not
      specifically attributable to HIV increased: liver disease (5.8% to 13.0%), kidney
      disease (7.9% to 12.0%), and heart disease (4.9% to 10.2%). CONCLUSION: Among
      deaths reported with HIV, the percentages reported with HIV-attributable diseases
      decreased, while the percentages reported with other diseases increased.
      Consequently, these other life-threatening diseases need more attention in the
      management of HIV-infected persons.

PMID- 21088285
TI  - Myocyte turnover in the aging human heart.
AB  - RATIONALE: The turnover of cardiomyocytes in the aging female and male heart is
      currently unknown, emphasizing the need to define human myocardial biology.
      OBJECTIVE: The effects of age and gender on the magnitude of myocyte regeneration
      and the origin of newly formed cardiomyocytes were determined. METHODS AND
      RESULTS: The interaction of myocyte replacement, cellular senescence, growth
      inhibition, and apoptosis was measured in normal female (n=32) and male (n=42)
      human hearts collected from patients 19 to 104 years of age who died from causes
      other than cardiovascular diseases. A progressive loss of telomeric DNA in human
      cardiac stem cells (hCSCs) occurs with aging and the newly formed cardiomyocytes
      inherit short telomeres and rapidly reach the senescent phenotype. Our data
      provide novel information on the superior ability of the female heart to sustain
      the multiple variables associated with the development of the senescent myopathy.
      At all ages, the female heart is equipped with a larger pool of functionally
      competent hCSCs and younger myocytes than the male myocardium. The replicative
      potential is higher and telomeres are longer in female hCSCs than in male hCSCs.
      In the female heart, myocyte turnover occurs at a rate of 10%, 14%, and 40% per
      year at 20, 60, and 100 years of age, respectively. Corresponding values in the
      male heart are 7%, 12%, and 32% per year, documenting that cardiomyogenesis
      involves a large and progressively increasing number of parenchymal cells with
      aging. From 20 to 100 years of age, the myocyte compartment is replaced 15 times
      in women and 11 times in men. CONCLUSIONS: The human heart is a highly dynamic
      organ regulated by a pool of resident hCSCs that modulate cardiac homeostasis and
      condition organ aging.

PMID- 21088286
TI  - Determinants and prognostic significance of electrocardiographic left ventricular
      hypertrophy criteria in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis of left ventricular hypertrophy (LVH)
      has prognostic value in the general population. However, among those with chronic
      kidney disease (CKD), the determinants of electrocardiographic (EKG) LVH and its
      prognostic value are not clear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      cross-sectional study was performed among 387 consenting consecutive patients
      from a veterans hospital with a longitudinal follow-up. RESULTS: The overall
      prevalence of EKG-LVH by the Sokolow-Lyon criteria was 8% and by the Cornell
      voltage-duration product was 11%. Compared with non-CKD controls, CKD patients
      had unadjusted odds ratio (OR) for LVH by Cornell criteria of 2.52 (95% CI 1.18
      to 5.42). Significance was lost after adjustment. The unadjusted OR for LVH by
      Sokolow-Lyon criteria was 2.24 (95% CI 0.95 to 5.33). This OR remained
      statistically insignificant after multivariate adjustment. Anemia, proteinuria,
      and 24-hour ambulatory systolic BP were associated with EKG-LVH regardless of
      diagnostic criteria. After a 7.5-year median follow-up, the hazard ratio for all
      cause mortality was not associated with EKG-LVH diagnosed by the Sokolow-Lyon
      criteria; however, multivariable adjustments made EKG-LVH significant. A
      statistically significant relationship was seen between mortality and Cornell
      criteria; however, multivariable adjustments made EKG-LVH nonsignificant.
      CONCLUSIONS: The Sokolow-Lyon and Cornell EKG-LVH criteria cannot be used
      interchangeably to diagnose LVH or determine prognosis. Among those with CKD,
      ambulatory systolic BP predicts all-cause mortality. Moreover, the duration and
      severity of BP elevation presumably reflected in EKG-LVH diagnosed by Sokolow
      Lyon criteria is also of prognostic significance; the Cornell criteria do not
      carry independent prognostic information.

PMID- 21088287
TI  - Single time point immune function assay (ImmuKnow) testing does not aid in the
      prediction of future opportunistic infections or acute rejection.
AB  - BACKGROUND AND OBJECTIVES: Current assays and tests that are used to determine
      the degree of immunosuppression in renal transplant recipients are suboptimal.
      The ImmuKnow assay (Cylex), a measure of intracellular CD4+ T cell ATP release
      proposed as a means to quantify cell-mediated immunity in transplant recipients,
      could be considered as a potential tool to identify patients at risk for
      opportunistic infections (OI) or acute rejection (AR). DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We retrospectively analyzed 1330 ImmuKnow assay
      values in 583 renal transplant recipients at a single center from 2004 to 2009
      and correlated these values with episodes of OI and AR in the subsequent 90 days.
      Assay values were compared with a control population matched for age, gender, and
      time post-transplantation. RESULTS: In patients with OI (n=94), there were no
      differences in prior mean assay values compared with matched controls (386 versus
      417 ng/ml, P=0.24). In 47 patients with AR, again no differences were detected in
      prior assay results (390 versus 432 ng/ml, P=0.25) when compared with controls.
      "Low" values (<=225 ng/ml) lacked sensitivity and specificity as a predictive
      test for subsequent OI, as did "strong" (>=525 ng/ml) values as a predictive test
      for subsequent AR. CONCLUSIONS: Our results fail to show an association between
      single time point ImmuKnow assay values and the subsequent development of an
      adverse event in the subsequent 90 days. The optimal use of the ImmuKnow assay in
      kidney transplantation has yet to be determined.

PMID- 21088288
TI  - Decreased cumulative access survival in arteriovenous fistulas requiring
      interventions to promote maturation.
AB  - BACKGROUND AND OBJECTIVES: New arteriovenous fistulas (AVF) are frequently
      unsuitable for hemodialysis because of AVF nonmaturation. Aggressive endovascular
      or surgical interventions are often undertaken to salvage nonmaturing AVFs. The
      effect of early interventions to promote AVF maturation on subsequent long-term
      AVF outcomes is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      evaluated 173 hemodialysis patients from two academic centers who received a new
      AVF. Of these, 96 (56%) required no further intervention, 54 (31%) required one
      intervention, and 23 (13%) required two or more interventions to achieve
      suitability for dialysis. We calculated AVF survival and frequency of
      postmaturation interventions in each group. RESULTS: Cumulative AVF survival
      (access cannulation to permanent failure) in patients with two or more versus one
      versus zero interventions before maturation was 68% versus 78% versus 92% at 1
      year, 57% versus 71% versus 85% at 2 years, and 42% versus 57% versus 75% at 3
      years. Using Cox regression analysis with interventions before maturation, age,
      sex, race, diabetes, peripheral vascular disease, access site, and obesity in the
      model, intervention before maturation (two or more) was the only factor
      associated with cumulative AVF survival. The number of interventions required to
      maintain patency after maturation was 3.51 +/- 2.20 versus 1.37 +/- 0.31 versus
      0.76 +/- 0.10 per year in patients with two or more versus one versus zero
      interventions before maturation. CONCLUSIONS: Compared with AVF that mature
      without interventions, AVF that require interventions have decreased cumulative
      survival and require more interventions to maintain their patency for
      hemodialysis.

PMID- 21088289
TI  - Nonlinear relationship between mycophenolate mofetil dose and mycophenolic acid
      exposure: implications for therapeutic drug monitoring.
AB  - BACKGROUND AND OBJECTIVES: Mycophenolate mofetil (MMF) is an immunosuppressive
      drug used in renal transplant patients. Upon oral administration it is hydrolyzed
      to the active agent mycophenolic acid (MPA). In renal transplant recipients, MMF
      therapy is optimal when the area under the curve of MPA is 30 to 60 mg.h/L. When
      MMF doses are adjusted, a linear relationship between dose and MPA exposure is
      assumed. In this study, the linearity of MMF pharmacokinetics was investigated.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MPA concentration-time profiles
      from renal transplant recipients cotreated with cyclosporine (n = 140) or
      tacrolimus (n = 101) were analyzed retrospectively using nonlinear mixed-effects
      modeling. The correlation between the MMF dose and the pharmacokinetics
      parameters was evaluated. RESULTS: In the developed population pharmacokinetics
      model MPA clearance and the central volume of distribution were correlated with
      cyclosporine coadministration and time posttransplantation. The pharmacokinetics
      of MPA were not linear. Bioavailability decreased with increasing MMF doses.
      Compared with an MMF dose of 1000 mg (=100%), relative bioavailability was 123%,
      111%, 94%, and 90% in patients receiving MMF doses of 250, 500, 1500, and 2000 mg
      in combination with cyclosporine (P < 0.001); respective values in tacrolimus
      cotreated patients were 176%, 133%, 85%, and 76% (P < 0.001). Because of the
      decreasing relative bioavailability, MPA exposure will increase less than
      proportionally with increasing MMF doses. CONCLUSIONS: MMF exhibits nonlinear
      pharmacokinetics. This should be taken into account when performing therapeutic
      drug monitoring.

PMID- 21088290
TI  - Potentially modifiable factors affecting the progression of autosomal dominant
      polycystic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The Consortium for Radiologic Imaging Studies of
      Polycystic Kidney Disease (CRISP) was created to identify markers of disease
      progression in patients with autosomal dominant polycystic kidney disease
      (ADPKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Linear mixed models were
      utilized to model effects of baseline parameters on changes in natural-log (ln)
      transformed total kidney volume (TKV) and iothalamate clearance (GFR) across time
      in CRISP participants (creatinine clearance at entry >70 ml/min). Stepwise
      selection was used to obtain a final main effect model. RESULTS: TKV increased
      from year to year, whereas GFR uncorrected for body surface area (BSA) decreased
      only at year 6. Higher lnTKV and urine sodium excretion (U(Na)V), lower serum HDL
      cholesterol, and younger age at baseline associated with greater lnTKV growth
      from baseline to year 3 and to year 6. Higher lnTKV at baseline associated with
      greater GFR decline from year 1 to year 3 and to year 6. Higher BSA and 24-hour
      urine osmolality at baseline associated with greater GFR decline from year 1 to
      year 6. Higher U(Na)V and lower serum HDL-cholesterol at baseline associated with
      greater GFR decline from year 1 to year 6 by univariate analysis only.
      Associations seen during year 1 to year 6 (not seen during year 1 to year 3)
      reflect the time lag between structural and functional disease progression.
      CONCLUSIONS: Serum HDL-cholesterol, U(Na)V, and 24-hour urine osmolality likely
      affect ADPKD progression. To what extent their modification may influence the
      clinical course of ADPKD remains to be determined.

PMID- 21088291
TI  - Microvolt T-wave alternans in end-stage renal disease patients--associations with
      uremic cardiomyopathy.
AB  - BACKGROUND AND OBJECTIVES: Premature cardiovascular (CV) events, especially
      sudden cardiac death, are common in ESRD patients and associated with uremic
      cardiomyopathy. Identification of high-risk patients is difficult. Microvolt T
      wave alternans (MTWA) is a noninvasive method of detecting variability in
      electrocardiogram (ECG) T-wave morphology and is a promising technique for
      identifying patients at high risk of ventricular tachyarrhythmias. MTWA results
      of ESRD and hypertensive left ventricular hypertrophy (LVH) patients were
      assessed to determine the prevalence of abnormal results and associations with
      uremic cardiomyopathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this
      single-center observational study, 200 ESRD and 30 LVH patients underwent
      assessment including CV history, ECG, cardiac magnetic resonance imaging, and an
      MTWA exercise test. MTWA results were classified as "negative" or "abnormal" on
      the basis of previously published reports. RESULTS: An abnormal MTWA result was
      more common in ESRD compared with LVH patients (57.5% versus 26.7%, respectively;
      P = 0.002). In ESRD patients, MTWA was significantly associated with uremic
      cardiomyopathy, clinical history of atherosclerosis (coronary, cerebral,
      peripheral) and diabetes mellitus, older age, and hemodialysis therapy.
      Independent associations with an abnormal MTWA result were older age,
      macrovascular disease, increased left ventricle (LV) mass, and LV dilation.
      CONCLUSIONS: Features of uremic cardiomyopathy are associated with an abnormal
      MTWA result.

PMID- 21088293
TI  - Prediction modeling to assess the prognostic significance of a biomarker panel.

PMID- 21088292
TI  - Folic acid therapy and cardiovascular disease in ESRD or advanced chronic kidney
      disease: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: The efficacy of folic acid therapy to lower
      homocysteine (Hcy) levels in an effort to reduce cardiovascular disease (CVD)
      risk in patients with ESRD or advanced chronic kidney disease (ACKD; creatinine
      clearance, <30 ml/min) remains inconclusive. We conducted a meta-analysis of
      relevant randomized trials to further examine this issue. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This meta-analysis included 3886 patients with
      ESRD/ACKD from seven qualified randomized trials using folic acid therapy and
      with CVD reported as one of the end points. RESULTS: When pooling the seven
      trials, folic acid therapy reduced the risk of CVD by 15% (RR, 0.85; 95% CI, 0.76
      to 0.96; P = 0.009). A greater beneficial effect was observed among those trials
      with a treatment duration >24 months (RR, 0.84; 95% CI, 0.72 to 0.98; P = 0.02),
      a decrease in Hcy level >20% (RR, 0.83; 95% CI, 0.73 to 0.95; P = 0.007), and no
      or partial folic acid fortification (RR, 0.80; 95% CI, 0.65 to 0.99; P = 0.04).
      The beneficial effect also was seen when Hcy levels decreased >20%, even in the
      presence of folic acid fortification (RR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04).
      In the corresponding comparison groups, the estimated RRs were attenuated and
      insignificant. CONCLUSIONS: Folic acid therapy can reduce CVD risk in patients
      with ESRD/ACKD by 15%. A greater beneficial effect was observed among those
      trials with no or partial folic acid fortification or a decrease in Hcy level
      >20% regardless of folic acid fortification.

PMID- 21088294
TI  - Molecular basis of decreased Kir4.1 function in SeSAME/EAST syndrome.
AB  - SeSAME/EAST syndrome is a channelopathy consisting of a hypokalemic,
      hypomagnesemic, metabolic alkalosis associated with seizures, sensorineural
      deafness, ataxia, and developmental abnormalities. This disease links to
      autosomal recessive mutations in KCNJ10, which encodes the Kir4.1 potassium
      channel, but the functional consequences of these mutations are not well
      understood. In Xenopus oocytes, all of the disease-associated mutant channels
      (R65P, R65P/R199X, G77R, C140R, T164I, and A167V/R297C) had decreased K(+)
      current (0 to 23% of wild-type levels). Immunofluorescence demonstrated decreased
      surface expression of G77R, C140R, and A167V expressed in HEK293 cells. When we
      coexpressed mutant and wild-type subunits to mimic the heterozygous state, R199X,
      C140R, and G77R currents decreased to 55, 40, and 20% of wild-type levels,
      respectively, suggesting that carriers of these mutations may present with an
      abnormal phenotype. Because Kir4.1 subunits can form heteromeric channels with
      Kir5.1, we coexpressed the aforementioned mutants with Kir5.1 and found that
      currents were reduced at least as much as observed when we expressed mutants
      alone. Reduction of pH(i) from approximately 7.4 to 6.8 significantly decreased
      currents of all mutants except R199X but did not affect wild-type channels. In
      conclusion, perturbed pH gating may underlie the loss of channel function for the
      disease-associated mutant Kir4.1 channels and may have important physiologic
      consequences.

PMID- 21088295
TI  - Local renal autoantibody production in lupus nephritis.
AB  - Autoantibodies are central to the pathogenesis of several autoimmune diseases
      including systemic lupus erythematosus. Plasma cells secrete these
      autoantibodies, but the anatomical sites of these cells are not well defined.
      Here, we found that although dsDNA-specific plasma cells in NZB/W mice were
      present in spleen and bone marrow, a large number were in the kidneys and their
      number correlated with the serum dsDNA-IgG titer. We observed renal plasma cells
      only in mice with nephritis, where they located mainly to the tubulointerstitium
      of the cortex and outer medulla. These cells had the phenotypic characteristics
      of fully differentiated plasma cells and, similar to long-lived bone marrow
      plasma cells, they were not in cell cycle. In patients with lupus nephritis,
      plasma cells were often present in the medulla in those with the most severe
      disease, especially combined proliferative and membranous lupus nephritis. The
      identification of the kidney as a major site of autoreactive plasma cells has
      implications for our understanding of the pathogenesis of lupus nephritis and for
      strategies to deplete autoreactive plasma cells, a long-standing therapeutic aim.

PMID- 21088296
TI  - Activation state of alpha4beta1 integrin on sickle red blood cells is linked to
      the duffy antigen receptor for chemokines (DARC) expression.
AB  - In sickle cell anemia, reticulocytes express enhanced levels of alpha4beta1
      integrin that interact mainly with vascular cell adhesion molecule-1 and
      fibronectin, promoting vaso-occlusion. These interactions are known to be highly
      sensitive to the inflammatory chemokine IL-8. The Duffy antigen receptor for
      chemokines (DARC) modulates the function of inflammatory processes. However, the
      link between alpha4beta1 activation by chemokines and DARC erythroid expression
      is not or poorly explored. Therefore, the capacity of alpha4beta1 to mediate
      Duffy-negative and Duffy-positive sickle reticulocyte (SRe) adhesion to
      immobilized vascular cell adhesion molecule-1 and fibronectin was evaluated.
      Using static adhesion assays, we found that, under basal conditions, Duffy
      positive SRe adhesion was 2-fold higher than that of Duffy-negative SRes.
      Incubating the cells with IL-8 or RANTES (regulated on activation normal T cell
      expressed and secreted) increased Duffy-positive SRe adhesion only, whereas
      Mn(2+) increased cell adhesion independently of the Duffy phenotype. Flow
      cytometry analyses performed with anti-beta1 and anti-alpha4 antibodies,
      including a conformation-sensitive one, in the presence or absence of IL-8,
      revealed that Duffy-positive and Duffy-negative SRes displayed similar erythroid
      alpha4beta1 expression levels, but with distinct activation states. IL-8 did not
      affect alpha4beta1 affinity in Duffy-positive SRes but induced its clustering as
      corroborated by immunofluorescence microscopy. Our results indicate that in Duffy
      negative SRes alpha4beta1 integrin is constitutively expressed in a low affinity
      state, whereas in Duffy-positive SRes alpha4beta1 is expressed in a higher
      chemokine-sensitive affinity state. This activation state associated with DARC
      RBC expression may influence the intensity of the inflammatory responses
      encountered in sickle cell anemia and participate in its interindividual clinical
      expression variability.

PMID- 21088298
TI  - The biosynthesis characteristics of TTP and TNF can be regulated through a
      posttranscriptional molecular loop.
AB  - The abundant expression of tumor necrosis factor (TNF) is a hallmark of chronic
      inflammation of the gastrointestinal tract. Prolonged inflammation can lead to
      inflammatory bowel disease. TNF biosynthesis is regulated both at transcription
      and posttranscriptional levels. However, the stimulation-induced increase in
      translation rate is much larger. This might indicate the possibility of a
      posttranscriptional regulatory mechanism. How, during basal conditions, is the
      free concentration of TNF tightly regulated at low levels? The stability and
      translational efficiency of TNF transcript are regulated by an AU-rich element
      (ARE) in the 3'-UTR of messenger RNA. A transacting protein, TTP, binds to ARE
      and enhances the mRNA turnover. Here, we examine a proposal that TNF homeostasis
      is regulated by a TTP-TNF interaction loop at the posttranscriptional level. We
      propose a computational framework of this regulatory loop by modeling the role of
      AREs in mediating the messenger RNA stability and translation. This
      posttranscriptional regulatory loop between TTP and TNF is composed of two
      feedback loops (i.e. positive and negative). The mutual interaction of these
      feedback loops regulates the biosynthesis response of TNF during basal and
      inflammatory conditions. Here, we also propose an explanation for why the p38
      inhibitors become insensitive for TTP knock-out mice.

PMID- 21088297
TI  - Abscisic acid regulates inflammation via ligand-binding domain-independent
      activation of peroxisome proliferator-activated receptor gamma.
AB  - Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and
      inflammation; however, its molecular targets and the mechanisms of action
      underlying its immunomodulatory effects remain unclear. This study investigates
      the role of peroxisome proliferator-activated receptor gamma (PPAR gamma) and
      lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We
      demonstrate that ABA increases PPAR gamma reporter activity in RAW 264.7
      macrophages and increases ppar gamma expression in vivo, although it does not
      bind to the ligand-binding domain of PPAR gamma. LANCL2 knockdown studies provide
      evidence that ABA-mediated activation of macrophage PPAR gamma is dependent on
      lancl2 expression. Consistent with the association of LANCL2 with G proteins, we
      provide evidence that ABA increases cAMP accumulation in immune cells. ABA
      suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR gamma
      dependent mechanism possibly involving activation of PPAR gamma and suppression
      of NF-kappaB and nuclear factor of activated T cells. LPS challenge studies in
      PPAR gamma-expressing and immune cell-specific PPAR gamma null mice demonstrate
      that ABA down-regulates toll-like receptor 4 expression in macrophages and T
      cells in vivo through a PPAR gamma-dependent mechanism. Global transcriptomic
      profiling and confirmatory quantitative RT-PCR suggest novel candidate targets
      and demonstrate that ABA treatment mitigates the effect of LPS on the expression
      of genes involved in inflammation, metabolism, and cell signaling, in part,
      through PPAR gamma. In conclusion, ABA decreases LPS-mediated inflammation and
      regulates innate immune responses through a bifurcating pathway involving LANCL2
      and an alternative, ligand-binding domain-independent mechanism of PPAR gamma
      activation.

PMID- 21088299
TI  - Reliability and validity of the Sedentary Behavior Questionnaire (SBQ) for
      adults.
AB  - BACKGROUND: Sedentary behavior is related to obesity, but measures of sedentary
      behaviors are lacking for adults. The purpose of this study was to examine the
      reliability and validity of the Sedentary Behavior Questionnaire (SBQ) among
      overweight adults. METHODS: Participants were 49 adults for the 2 week test
      retest reliability study (67% female, 53% white, mean age = 20) and 401
      overweight women (mean age = 41, 61% white) and 441 overweight men (mean age =
      44, 81% white) for the validity study. The SBQ consisted of reports of time spent
      in 9 sedentary behaviors. Outcomes for validity included accelerometer measured
      inactivity, sitting time (International Physical Activity Questionnaire), and
      BMI. Intraclass correlation coefficients (ICCs) assessed reliability and partial
      correlations assessed validity. RESULTS: ICCs were acceptable for all items and
      the total scale (range = .51-.93). For men, there were significant relationships
      of SBQ items with IPAQ sitting time and BMI. For women, there were relationships
      between the SBQ and accelerometer inactivity minutes, IPAQ sitting time, and BMI.
      CONCLUSIONS: The SBQ has acceptable measurement properties for use among
      overweight adults. Specific measures of sedentary behavior should be included in
      studies and population surveillance.

PMID- 21088300
TI  - Invariance of wearing location of Omron-BI pedometers: a validation study.
AB  - BACKGROUND: The purpose of this study was to investigate the validity and
      reliability evidences of the Omron BI pedometer, which could count steps taken
      even when worn at different locations on the body. METHODS: Forty (20 males and
      20 females) adults were recruited to walk wearing 5 sets, 1 set at a time, of 10
      BI pedometers during testing, 1 each at 10 different locations. For comparison,
      they also wore 2 Yamax Digi-Walker SW-200 pedometers and a Dynastream AMP 331
      activity monitor. The subjects walked in 3 free-living conditions: a flat
      sidewalk, stairs, and mixed conditions. RESULTS: Except for a slight decrease in
      accuracy in the pant pocket locations, Omron BI pedometers counted steps
      accurately across other locations when subjects walked on the flat sidewalk, and
      the performance was consistent across devices and trials. When the subjects
      climbed up stairs, however, the absolute error % of the pant pocket locations
      increased significantly (P < .05) and similar or higher error rates were found in
      the AMP 331 and SW-200s. CONCLUSIONS: The Omron BI pedometer can accurately count
      steps when worn at various locations on the body in free-living conditions except
      for front pant pocket locations, especially when climbing stairs.

PMID- 21088301
TI  - Physical activity levels by occupational category in non-metropolitan Australian
      adults.
AB  - BACKGROUND: The aim of this study was to examine the relationship between
      occupational category and 3 health-related behaviors: participation in leisure
      time physical activity, active transport (AT) and occupational sitting in a
      sample of employed Australian adults. METHODS: A random, cross-sectional sample
      of 592 adults aged 18 to 71 years completed a telephone survey in
      October/November 2006. Reported occupations were categorized as professional (n =
      332, 56.1%), white-collar (n = 181, 30.6%), and blue-collar (n = 79, 13.3%).
      Relationships between occupational category and AT, sufficient physical activity
      and occupational sitting were examined using logistic regression. RESULTS: White
      collar employees (OR = 0.36, 95% CI 0.14-0.95) were less likely to engage in AT
      and more likely to engage in occupational sitting (OR = 3.10, 95% CI 1.63-5.92)
      when compared with blue-collar workers. Professionals (OR = 3.04, 95% CI 1.94
      4.76) were also more likely to engage in occupational sitting compared with blue
      collar workers. No relationship was observed between occupational category and
      engagement in sufficient physical activity. CONCLUSIONS: No association between
      occupational category and sufficient physical activity levels was observed,
      although white-collar and professionals were likely to engage in high levels of
      occupational sitting. Innovative and sustainable strategies are required to
      reduce occupational sitting to improve health.

PMID- 21088302
TI  - Step activity in persons with Parkinson's disease.
AB  - BACKGROUND: UPDRS and PDQ-39 are reliable and valid assessments of quality of
      life and physical function in persons with Parkinson's disease (PD). However,
      these measures were not designed to track day-to-day or week-to-week changes in
      community activity in persons with PD. METHODS: Twelve individuals with PD (stage
      1 to 3, Hoehn and Yahr) who were active members of a health and wellness facility
      were recruited for this study. Investigators collected health history
      information, asked questions about the amount and frequency of weekly exercise,
      and assessed motor symptoms and ADL skills using the UPDRS, and provided
      participants with Step Activity Monitor (SAM). SAM data were collected for a
      continuous 7-day period. RESULTS: Participants averaged 8996 steps/day, had an
      average of 322 minutes of step activity per day, but were inactive (minIA) 77% of
      their time per day. On the days that participants visited the health and wellness
      facility they took an average of 802 more steps with 12 minutes more activity per
      day. CONCLUSIONS: A SAM can be used to capture activity levels in persons with
      PD. These pilot data indicate that persons with mild to moderate PD can achieve
      step activity levels similar to healthy older adults.

PMID- 21088303
TI  - Step counts of non-white minority children and youth by gender, grade level,
      race/ethnicity, and mode of school transportation.
AB  - BACKGROUND: The purposes of this study were to describe and analyze the steps/d
      of nonwhite minority children and youth by gender, grade level, race/ethnicity,
      and mode of school transportation. A secondary purpose was to compare the steps/d
      of minority children and youth to their Caucasian grade-level counterparts.
      METHODS: Participants were 547 minority youth grades 5 to 8 from 4 urban schools.
      Participants wore sealed pedometers for 6 consecutive week/school days. Three
      hundred and ten participants responded to a questionnaire concerning their mode
      of transportation to and from school. RESULTS: Statistical analyses indicated a
      main effect for gender (F(3, 546) = 13.50, P < .001) with no interaction. Boys
      (12,589 +/- 3921) accumulated significantly more steps/d than girls (9,539 +/-
      3,135). Further analyses also revealed a significant main effect for mode of
      school transportation (F(2, 309) = 15.97, P <= .001). Walkers (12,614 +/- 4169)
      obtained significantly more steps/d than car (10,021 +/- 2856) or bus (10,230 +/-
      3666) transit users. CONCLUSIONS: Minority boys obtain similar steps/d as their
      Caucasian grade-level counterparts; minority girls obtain less steps/d than their
      Caucasian grade-level counterparts. Minority youth who actively commute are more
      likely to meet PA recommendations than nonactive commuters.

PMID- 21088304
TI  - The effects of an incremental approach to 10,000 steps/day on metabolic syndrome
      components in sedentary overweight women.
AB  - BACKGROUND: Pedometer programs can increase physical activity in sedentary
      individuals, a population that is at risk for developing metabolic syndrome and
      each of its individual components. Although the popular 10,000 steps/day
      recommendation has shown to induce many favorable health benefits, it may be out
      of reach for sedentary individuals. This study observed the effects of
      incremental increases in steps/day on metabolic syndrome components in sedentary
      overweight women. METHODS: This study was a longitudinal, quasi-experimental
      design. Participants were recruited from a 12-week work-site pedometer program
      and grouped as either 'active' or 'control' after the intervention based on their
      steps/day improvement. Self-reported physical activity, pedometer assessed
      physical activity, BMI, resting heart rate, waist circumference, blood pressure,
      triglycerides, HDL-C, and fasting glucose were measured before and after the
      program. RESULTS: The active group showed significant within-group improvements
      in waist circumference and fasting glucose. Significant group differences were
      observed in resting heart rate, BMI, and systolic blood pressure; however, the
      changes observed in systolic blood pressure were not independent of weight loss.
      CONCLUSIONS: Incremental increases in steps/day induced favorable changes in some
      MetS components suggesting that this approach is a viable starting point for
      sedentary individuals that may find it difficult to initially accumulate 10,000
      steps/day.

PMID- 21088305
TI  - Associations of cardiorespiratory fitness and fatness with cardiovascular risk
      factors among adolescents: the NHANES 1999-2002.
AB  - BACKGROUND: This study aimed to examine combined and independent effects of
      cardiorespiratory fitness and fatness on cardiovascular risk factors among U.S.
      adolescents. METHODS: Data from adolescents age 12 to 19 years participating in
      the NHANES 1999 to 2002 were used. Fitness level was determined by submaximal
      treadmill test and was dichotomized as 'not fit' or 'fit' according to the
      FITNESSGRAM. Fatness level was categorized as 'not fat' or 'fat' based on the CDC
      BMI growth charts. Gender-specific multivariable linear regression analyses were
      conducted to compare age-, race/ethnicity-, fatness-, and waist circumference
      adjusted means of blood pressure, lipids, lipoproteins, C-peptide, insulin, and C
      reactive protein (CRP) levels. RESULTS: A total of 3202 adolescents (1629 boys)
      were included for data analysis. Among boys, total cholesterol, triglycerides,
      insulin, and CRP mean levels were significantly higher (P < .05) in the 'not fit'
      group than in the 'fit' group, after adjustment for fatness level and waist
      circumference. Among girls, the fatness level- and waist circumference-adjusted
      means of total cholesterol (P < .01) and LDL-C (P < .09) were higher in the 'not
      fit' than 'fit' groups. CONCLUSION: Cardiorespiratory fitness, independent of
      fatness, may have beneficial effects on lipid profiles among girls, and on lipid
      profiles, insulin metabolism, and inflammation levels among boys.

PMID- 21088306
TI  - The physical activity behaviors outside school and BMI in adolescents.
AB  - BACKGROUND: The aim of this study is to investigate the associations between
      active transport (AT), nonorganized out of school physical activity (NOPA) and
      organized out of school PA (OPA) with BMI in Portuguese adolescents. METHODS: The
      sample comprised 1121 adolescents age 13 to 17 years-old, which were assigned to
      1 of 4 PA groups according to the sum of participation in different physical
      activity behaviors outside of school [AT, OPA, and NOPA]. RESULTS: In boys but
      not in girls, BMI was lower as the participation in more PA behaviors outside
      school increased. For those who only carry out 1 PA behavior, AT was the most
      common behavior (boys = 48.9%; girls = 55.1%). On the other hand, NOPA was the
      most common behavior for those engaged in 2 types of PA (girls = 51.6%; boys =
      46%). For those that carried out all the PA behaviors outside school OPA was the
      most common choice in both girls (59.5%) and boys (54%). AT, NOPA and OPA are
      different sources of PA outside school that accrued in different ways to the
      increased level of PA. CONCLUSIONS: In boys but not in girls, BMI was lower as
      the participation in more PA behaviors outside school increased.

PMID- 21088308
TI  - Adolescent gender and ethnicity differences in physical activity perceptions and
      behavior.
AB  - OBJECTIVES: To examine gender and ethnicity differences in adolescents' physical
      activity (PA) behavior and perceptions. METHODS: Surveys designed to measure PA
      behavior and perception were completed by 175 adolescents. Gender and ethnicity
      differences in PA behavior were examined using chi-square tests. A two-way
      between groups MANOVA was used to examine perception. RESULTS: No significant
      differences were found between gender groups for PA. Caucasian students were more
      likely to be active and to perceive that PA makes their health better. Hispanics
      were more likely to perceive that PA requires more time than Caucasians.
      CONCLUSIONS: Findings suggest greater consideration be given to the ethnic
      orientation of PA behavior antecedents when promoting PA to adolescents.

PMID- 21088307
TI  - Physical activity and injuries during pregnancy.
AB  - BACKGROUND: Although physical activity can provide health benefits to pregnant
      women, population-based research on the circumstances surrounding injuries from
      physical activity during pregnancy is lacking. METHODS: Physical activity and
      subsequent injuries among a cohort of 1469 pregnant women in North Carolina were
      examined prospectively from the third phase of the Pregnancy, Infection, and
      Nutrition Study between 2001 and 2005. Chi-square analyses were used to compare
      distributions of maternal characteristics among women who sustained injuries from
      physical activity and women who reported no injuries during pregnancy. Injury
      incidence rates were calculated. RESULTS: Few pregnant women (N = 34) reported a
      physical activity-related injury during pregnancy. The rates of physical activity
      related and exercise-related injuries during pregnancy were 3.2 per 1000 physical
      activity hours and 4.1 per 1000 exercise hours, respectively. The most common
      types of injuries were bruises or scrapes (55%). Among all injuries, 33% resulted
      from exercise and 67% resulted from nonexercise physical activities. Sixty-four
      percent of all injuries were due to falls. CONCLUSIONS: The incidence of injury
      from physical activity was low during pregnancy. Women should continue to be
      encouraged to maintain involvement in physical activity during pregnancy, while
      being aware of the potential for injury, particularly falls, from these
      activities.

PMID- 21088309
TI  - Correlates of children and parents being physically active together.
AB  - BACKGROUND: Co-physical activity (between parents and children), as an outcome
      variable, and its correlates have not been examined previously. The purpose of
      this study was to investigate correlates of co-physical activity among a
      nationally representative sample of 9- to 13-year-old children and their parents.
      METHODS: Data were from the 2004 Youth Media Campaign Longitudinal Survey, a
      national survey of 5177 child-parent dyads. Parents of 9- to 13-year-old children
      were asked to report co-physical activity. Parents and children responded to a
      series of sociodemographic, behavioral, and psychosocial measures. Co-physical
      activity was treated as a dichotomous variable (ie, some or none). Logistic
      regression was used to assess associations of correlates directly and possible
      interactions between correlates. RESULTS: More than three-quarters of parents
      reported co-physical activity at least 1 day in the prior week. Age,
      race/ethnicity, sports team participation, eating meals together, parental
      confidence to influence the child's organized activity, and the child's
      perception of parental support were significantly associated with co-physical
      activity. CONCLUSION: The majority of respondents reported participating in co
      physical activity, and multiple sociodemographic, behavioral, and psychosocial
      correlates were significantly associated with co-physical activity. This study
      provides insight for physical activity interventions that might involve parents.

PMID- 21088310
TI  - An acute exercise session increases self-efficacy in sedentary endometrial cancer
      survivors and controls.
AB  - BACKGROUND: Self-efficacy can be affected by mastery experiences and somatic
      sensations. A novel exercise experience and associated sensations may impact self
      efficacy and subsequent behaviors. We investigated the effect of a single
      exercise session on self-efficacy for sedentary endometrial cancer survivors
      compared with sedentary women of a similar age, but with no cancer history.
      METHODS: Twenty survivors and 19 controls completed an exercise session performed
      as a submaximal cycle ergometry test. Sensations and efficacy were measured
      before and after exercise. Repeated measures analysis of variance (ANOVA) was
      performed. Regression models were used to determine predictors of self-efficacy
      and subsequent exercise. RESULTS: Self-efficacy increased for both survivors and
      controls, but survivors had a higher rate of increase, and the change predicted
      subsequent exercise. The association between exercise-related somatic sensations
      and self-efficacy differed between the 2 groups. CONCLUSIONS: A novel exercise
      experience had a larger effect on self-efficacy and subsequent exercise activity
      for endometrial cancer survivors than controls. Somatic sensations experienced
      during exercise may differ for survivors, which may be related to the experience
      of having cancer. Understanding factors affecting confidence in novel exercise
      experiences for populations with specific cancer histories is of the utmost
      importance in the adoption of exercise behaviors.

PMID- 21088311
TI  - Development and assessment of a physical activity guidebook for the Colon Health
      and Life-Long Exercise Change (CHALLENGE) trial (NCIC CO.21).
AB  - BACKGROUND: We report the development and assessment of a physical activity (PA)
      guidebook called Step Up to the Challenge that is being used to support a PA
      behavior change intervention in a randomized trial examining PA and disease-free
      survival in colon cancer survivors. METHODS: Content for the PA guidebook was
      constructed based on the Theory of Planned Behavior (TPB). Expert judges (N = 51)
      included oncologists, rehabilitation practitioners, colon cancer survivors, and
      TPB researchers. All expert judges completed the Maine Area Health Education
      Center checklist for evaluating written health information. A subset of TPB
      expert judges (n = 11) also assessed the degree of match between the guidebook
      content and TPB constructs. RESULTS: Expert judges indicated that the PA
      guidebook achieved desirable attributes for organization, writing style,
      appearance, appeal, feasibility, and appropriateness. For the TPB assessment, all
      mean item-content relevance ratings indicated at least a "very good match"
      between the PA guidebook content and the TPB constructs. CONCLUSIONS: Our
      guidebook successfully targets the TPB constructs known to influence PA behavior
      change and contains suitable and appropriate written health information. This
      guidebook will be an integral component of the behavioral support program
      designed to determine the effects of PA on disease-free survival in colon cancer
      survivors.

PMID- 21088312
TI  - Perceived neighborhood environment and park use as mediators of the effect of
      area socio-economic status on walking behaviors.
AB  - BACKGROUND: Access to local parks can affect walking levels. Neighborhood
      environment and park use may influence relationships between neighborhood
      socioeconomic status (SES) and walking. METHODS: Self-report data on perceived
      park features, neighborhood environment, park use, neighborhood walking and
      sociodemographics were obtained from a sample of Australian adults, living in
      high/low SES areas. Surveys were mailed to 250 randomly selected households
      within 500m of 12 matched parks. Mediating effects of perceived environment
      attributes and park use on relationships between area-SES and walking were
      examined. RESULTS: Mean frequency of local park use was higher for high-SES
      residents (4.36 vs 3.16 times/wk, P < .01), who also reported higher levels of
      park safety, maintenance, attractiveness, opportunities for socialization, and
      neighborhood crime safety, aesthetics, and traffic safety. Safety and opportunity
      for socialization were independently positively related to monthly frequency of
      visits to a local park which, in turn, was positively associated with walking for
      recreation and total walking. Residents of higher SES areas reported an average
      22% (95% CI: 5%, 37%) more weekly minutes of recreational walking than their low
      SES counterparts. CONCLUSION: Residents of high-SES areas live in environments
      that promote park use, which positively contributes to their weekly amounts of
      overall and recreational walking.

PMID- 21088314
TI  - Examining public open spaces by neighborhood-level walkability and deprivation.
AB  - BACKGROUND: Public open spaces (POS) are recognized as important to promote
      physical activity engagement. However, it is unclear how POS attributes, such as
      activities available, environmental quality, amenities present, and safety, are
      associated with neighborhood-level walkability and deprivation. METHODS: Twelve
      neighborhoods were selected within 1 constituent city of Auckland, New Zealand
      based on higher (n = 6) or lower (n = 6) walkability characteristics.
      Neighborhoods were dichotomized as more (n = 7) or less (n = 5) socioeconomically
      deprived. POS (n = 69) were identified within these neighborhoods and audited
      using the New Zealand-Public Open Space Tool. Unpaired 1-way analysis of variance
      tests were applied to compare differences in attributes and overall score of POS
      by neighborhood walkability and deprivation. RESULTS: POS located in more
      walkable neighborhoods have significantly higher overall scores when compared
      with less walkable neighborhoods. Deprivation comparisons identified POS located
      in less deprived communities have better quality environments, but fewer
      activities and safety features present when compared with more deprived
      neighborhoods. CONCLUSIONS: A positive relationship existed between presence of
      POS attributes and neighborhood walkability, but the relationship between POS and
      neighborhood-level deprivation was less clear. Variation in neighborhood POS
      quality alone is unlikely to explain poorer health outcomes for residents in more
      deprived areas.

PMID- 21088315
TI  - Decomposition of complex line drawings with hidden lines for 3D planar-faced
      manifold object reconstruction.
AB  - Three-dimensional object reconstruction from a single 2D line drawing is an
      important problem in computer vision. Many methods have been presented to solve
      this problem, but they usually fail when the geometric structure of a 3D object
      becomes complex. In this paper, a novel approach based on a divide-and-conquer
      strategy is proposed to handle the 3D reconstruction of a planar-faced complex
      manifold object from its 2D line drawing with hidden lines visible. The approach
      consists of four steps: 1) identifying the internal faces of the line drawing, 2)
      decomposing the line drawing into multiple simpler ones based on the internal
      faces, 3) reconstructing the 3D shapes from these simpler line drawings, and 4)
      merging the 3D shapes into one complete object represented by the original line
      drawing. A number of examples are provided to show that our approach can handle
      3D reconstruction of more complex objects than previous methods.

PMID- 21088313
TI  - The physical activity climate in Minnesota middle and high schools.
AB  - BACKGROUND: This article describes policies, practices, and facilities that form
      the physical activity climate in Minneapolis/St. Paul, Minnesota metro area
      middle and high schools and examines how the physical activity climate varies by
      school characteristics, including public/private, school location and grade
      level. METHODS: Surveys examining school physical activity practices, policies
      and environment were administered to principals and physical education department
      heads from 115 middle and high schools participating in the Transdisciplinary
      Research on Energetics and Cancer-Identifying Determinants of Eating and Activity
      (TREC-IDEA) study. RESULTS: While some supportive practices were highly prevalent
      in the schools studied (such as prohibiting substitution of other classes for
      physical education); other practices were less common (such as providing
      opportunity for intramural (noncompetitive) sports). Public schools vs. private
      schools and schools with a larger school enrollment were more likely to have a
      school climate supportive of physical activity. CONCLUSIONS: Although schools
      reported elements of positive physical activity climates, discrepancies exist by
      school characteristics. Of note, public schools were more than twice as likely as
      private schools to have supportive physical activity environments. Establishing
      more consistent physical activity expectations and funding at the state and
      national level is necessary to increase regular school physical activity.

PMID- 21088316
TI  - Turbo segmentation of textured images.
AB  - We consider the problem of semi-supervised segmentation of textured images.
      Existing model-based approaches model the intensity field of textured images as a
      Gauss-Markov random field to take into account the local spatial dependencies
      between the pixels. Classical Bayesian segmentation consists of also modeling the
      label field as a Markov random field to ensure that neighboring pixels correspond
      to the same texture class with high probability. Well-known relaxation techniques
      are available which find the optimal label field with respect to the maximum a
      posteriori or the maximum posterior mode criterion. But, these techniques are
      usually computationally intensive because they require a large number of
      iterations to converge. In this paper, we propose a new Bayesian framework by
      modeling two-dimensional textured images as the concatenation of two one
      dimensional hidden Markov autoregressive models for the lines and the columns,
      respectively. A segmentation algorithm, which is similar to turbo decoding in the
      context of error-correcting codes, is obtained based on a factor graph approach.
      The proposed method estimates the unknown parameters using the Expectation
      Maximization algorithm.

PMID- 21088317
TI  - Bilayer segmentation of webcam videos using tree-based classifiers.
AB  - This paper presents an automatic segmentation algorithm for video frames captured
      by a (monocular) webcam that closely approximates depth segmentation from a
      stereo camera. The frames are segmented into foreground and background layers
      that comprise a subject (participant) and other objects and individuals. The
      algorithm produces correct segmentations even in the presence of large background
      motion with a nearly stationary foreground. This research makes three key
      contributions: First, we introduce a novel motion representation, referred to as
      "motons," inspired by research in object recognition. Second, we propose
      estimating the segmentation likelihood from the spatial context of motion. The
      estimation is efficiently learned by random forests. Third, we introduce a
      general taxonomy of tree-based classifiers that facilitates both theoretical and
      experimental comparisons of several known classification algorithms and generates
      new ones. In our bilayer segmentation algorithm, diverse visual cues such as
      motion, motion context, color, contrast, and spatial priors are fused by means of
      a conditional random field (CRF) model. Segmentation is then achieved by binary
      min-cut. Experiments on many sequences of our videochat application demonstrate
      that our algorithm, which requires no initialization, is effective in a variety
      of scenes, and the segmentation results are comparable to those obtained by
      stereo systems.

PMID- 21088318
TI  - Discriminative learning of local image descriptors.
AB  - In this paper, we explore methods for learning local image descriptors from
      training data. We describe a set of building blocks for constructing descriptors
      which can be combined together and jointly optimized so as to minimize the error
      of a nearest-neighbor classifier. We consider both linear and nonlinear
      transforms with dimensionality reduction, and make use of discriminant learning
      techniques such as Linear Discriminant Analysis (LDA) and Powell minimization to
      solve for the parameters. Using these techniques, we obtain descriptors that
      exceed state-of-the-art performance with low dimensionality. In addition to new
      experiments and recommendations for descriptor learning, we are also making
      available a new and realistic ground truth data set based on multiview stereo
      data.

PMID- 21088319
TI  - Flexible depth of field photography.
AB  - The range of scene depths that appear focused in an image is known as the depth
      of field (DOF). Conventional cameras are limited by a fundamental trade-off
      between depth of field and signal-to-noise ratio (SNR). For a dark scene, the
      aperture of the lens must be opened up to maintain SNR, which causes the DOF to
      reduce. Also, today's cameras have DOFs that correspond to a single slab that is
      perpendicular to the optical axis. In this paper, we present an imaging system
      that enables one to control the DOF in new and powerful ways. Our approach is to
      vary the position and/or orientation of the image detector during the integration
      time of a single photograph. Even when the detector motion is very small (tens of
      microns), a large range of scene depths (several meters) is captured, both in and
      out of focus. Our prototype camera uses a micro-actuator to translate the
      detector along the optical axis during image integration. Using this device, we
      demonstrate four applications of flexible DOF. First, we describe extended DOF
      where a large depth range is captured with a very wide aperture (low noise) but
      with nearly depth-independent defocus blur. Deconvolving a captured image with a
      single blur kernel gives an image with extended DOF and high SNR. Next, we show
      the capture of images with discontinuous DOFs. For instance, near and far objects
      can be imaged with sharpness, while objects in between are severely blurred.
      Third, we show that our camera can capture images with tilted DOFs (Scheimpflug
      imaging) without tilting the image detector. Finally, we demonstrate how our
      camera can be used to realize nonplanar DOFs. We believe flexible DOF imaging can
      open a new creative dimension in photography and lead to new capabilities in
      scientific imaging, vision, and graphics.

PMID- 21088320
TI  - Global ridge orientation modeling for partial fingerprint identification.
AB  - Identifying incomplete or partial fingerprints from a large fingerprint database
      remains a difficult challenge today. Existing studies on partial fingerprints
      focus on one-to-one matching using local ridge details. In this paper, we
      investigate the problem of retrieving candidate lists for matching partial
      fingerprints by exploiting global topological features. Specifically, we propose
      an analytical approach for reconstructing the global topology representation from
      a partial fingerprint. First, we present an inverse orientation model for
      describing the reconstruction problem. Then, we provide a general expression for
      all valid solutions to the inverse model. This allows us to preserve data
      fidelity in the existing segments while exploring missing structures in the
      unknown parts. We have further developed algorithms for estimating the missing
      orientation structures based on some a priori knowledge of ridge topology
      features. Our statistical experiments show that our proposed model-based approach
      can effectively reduce the number of candidates for pair-wised fingerprint
      matching, and thus significantly improve the system retrieval performance for
      partial fingerprint identification.

PMID- 21088321
TI  - Latent fingerprint matching.
AB  - Latent fingerprint identification is of critical importance to law enforcement
      agencies in identifying suspects: Latent fingerprints are inadvertent impressions
      left by fingers on surfaces of objects. While tremendous progress has been made
      in plain and rolled fingerprint matching, latent fingerprint matching continues
      to be a difficult problem. Poor quality of ridge impressions, small finger area,
      and large nonlinear distortion are the main difficulties in latent fingerprint
      matching compared to plain or rolled fingerprint matching. We propose a system
      for matching latent fingerprints found at crime scenes to rolled fingerprints
      enrolled in law enforcement databases. In addition to minutiae, we also use
      extended features, including singularity, ridge quality map, ridge flow map,
      ridge wavelength map, and skeleton. We tested our system by matching 258 latents
      in the NIST SD27 database against a background database of 29,257 rolled
      fingerprints obtained by combining the NIST SD4, SD14, and SD27 databases. The
      minutiae-based baseline rank-1 identification rate of 34.9 percent was improved
      to 74 percent when extended features were used. In order to evaluate the relative
      importance of each extended feature, these features were incrementally used in
      the order of their cost in marking by latent experts. The experimental results
      indicate that singularity, ridge quality map, and ridge flow map are the most
      effective features in improving the matching accuracy.

PMID- 21088322
TI  - Multiperson visual focus of attention from head pose and meeting contextual cues.
AB  - This paper introduces a novel contextual model for the recognition of people's
      visual focus of attention (VFOA) in meetings from audio-visual perceptual cues.
      More specifically, instead of independently recognizing the VFOA of each meeting
      participant from his own head pose, we propose to jointly recognize the
      participants' visual attention in order to introduce context-dependent
      interaction models that relate to group activity and the social dynamics of
      communication. Meeting contextual information is represented by the location of
      people, conversational events identifying floor holding patterns, and a
      presentation activity variable. By modeling the interactions between the
      different contexts and their combined and sometimes contradictory impact on the
      gazing behavior, our model allows us to handle VFOA recognition in difficult task
      based meetings involving artifacts, presentations, and moving people. We
      validated our model through rigorous evaluation on a publicly available and
      challenging data set of 12 real meetings (5 hours of data). The results
      demonstrated that the integration of the presentation and conversation dynamical
      context using our model can lead to significant performance improvements.

PMID- 21088323
TI  - Product quantization for nearest neighbor search.
AB  - This paper introduces a product quantization-based approach for approximate
      nearest neighbor search. The idea is to decompose the space into a Cartesian
      product of low-dimensional subspaces and to quantize each subspace separately. A
      vector is represented by a short code composed of its subspace quantization
      indices. The euclidean distance between two vectors can be efficiently estimated
      from their codes. An asymmetric version increases precision, as it computes the
      approximate distance between a vector and a code. Experimental results show that
      our approach searches for nearest neighbors efficiently, in particular in
      combination with an inverted file system. Results for SIFT and GIST image
      descriptors show excellent search accuracy, outperforming three state-of-the-art
      approaches. The scalability of our approach is validated on a data set of two
      billion vectors.

PMID- 21088324
TI  - Tracking with occlusions via graph cuts.
AB  - This work presents a new method for tracking and segmenting along time
      interacting objects within an image sequence. One major contribution of the paper
      is the formalization of the notion of visible and occluded parts. For each
      object, we aim at tracking these two parts. Assuming that the velocity of each
      object is driven by a dynamical law, predictions can be used to guide the
      successive estimations. Separating these predicted areas into good and bad parts
      with respect to the final segmentation and representing the objects with their
      visible and occluded parts permit handling partial and complete occlusions. To
      achieve this tracking, a label is assigned to each object and an energy function
      representing the multilabel problem is minimized via a graph cuts optimization.
      This energy contains terms based on image intensities which enable segmenting and
      regularizing the visible parts of the objects. It also includes terms dedicated
      to the management of the occluded and disappearing areas, which are defined on
      the areas of prediction of the objects. The results on several challenging
      sequences prove the strength of the proposed approach.

PMID- 21088325
TI  - Video registration using dynamic textures.
AB  - We consider the problem of spatially and temporally registering multiple video
      sequences of dynamical scenes which contain, but are not limited to, nonrigid
      objects such as fireworks, flags fluttering in the wind, etc., taken from
      different vantage points. This problem is extremely challenging due to the
      presence of complex variations in the appearance of such dynamic scenes. In this
      paper, we propose a simple algorithm for matching such complex scenes. Our
      algorithm does not require the cameras to be synchronized, and is not based on
      frame-by-frame or volume-by-volume registration. Instead, we model each video as
      the output of a linear dynamical system and transform the task of registering the
      video sequences to that of registering the parameters of the corresponding
      dynamical models. As these parameters are not uniquely defined, one cannot
      directly compare them to perform registration. We resolve these ambiguities by
      jointly identifying the parameters from multiple video sequences, and converting
      the identified parameters to a canonical form. This reduces the video
      registration problem to a multiple image registration problem, which can be
      efficiently solved using existing image matching techniques. We test our
      algorithm on a wide variety of challenging video sequences and show that it
      matches the performance of significantly more computationally expensive existing
      methods.

PMID- 21088326
TI  - View-independent action recognition from temporal self-similarities.
AB  - This paper addresses recognition of human actions under view changes. We explore
      self-similarities of action sequences over time and observe the striking
      stability of such measures across views. Building upon this key observation, we
      develop an action descriptor that captures the structure of temporal similarities
      and dissimilarities within an action sequence. Despite this temporal self
      similarity descriptor not being strictly view-invariant, we provide intuition and
      experimental validation demonstrating its high stability under view changes. Self
      similarity descriptors are also shown to be stable under performance variations
      within a class of actions when individual speed fluctuations are ignored. If
      required, such fluctuations between two different instances of the same action
      class can be explicitly recovered with dynamic time warping, as will be
      demonstrated, to achieve cross-view action synchronization. More central to the
      current work, temporal ordering of local self-similarity descriptors can simply
      be ignored within a bag-of-features type of approach. Sufficient action
      discrimination is still retained in this way to build a view-independent action
      recognition system. Interestingly, self-similarities computed from different
      image features possess similar properties and can be used in a complementary
      fashion. Our method is simple and requires neither structure recovery nor
      multiview correspondence estimation. Instead, it relies on weak geometric
      properties and combines them with machine learning for efficient cross-view
      action recognition. The method is validated on three public data sets. It has
      similar or superior performance compared to related methods and it performs well
      even in extreme conditions, such as when recognizing actions from top views while
      using side views only for training.

PMID- 21088327
TI  - Local vapor transport synthesis of zinc oxide nanowires for ultraviolet-enhanced
      gas sensing.
AB  - A novel local vapor transport technique via induction heating is presented to
      enable selective, localized synthesis and self-assembly of nanowires, providing a
      simple and fast method for the direct integration of nanowires into functional
      devices. The single-crystalline zinc oxide (ZnO) nanowires are grown locally
      across the silicon-on-insulator microelectrodes within minutes, and the
      enhancement of gas sensing of ZnO nanowires is demonstrated under ultraviolet
      (UV) illumination at room temperature. Experiments indicate that when suspended
      nanowires are exposed to UV light, a twelve-fold increase in conductance and a
      near five-fold improvement in oxygen response are measured. Furthermore, the UV
      enhanced transient responses exhibit a two-level photocurrent decay attributed to
      carrier recombination and oxygen readsorption. As such, the local vapor transport
      synthesis and UV-enhanced sensing scheme could provide a promising approach for
      the construction of miniaturized and highly responsive nanowire-based gas
      sensors.

PMID- 21088328
TI  - Sympathoinhibitory effects of atorvastatin in hypertension.

PMID- 21088329
TI  - The nitric oxide synthase family and left ventricular diastolic function.

PMID- 21088330
TI  - Energy States in mitochondrial cardiomyopathy. In vivo functional imaging and L
      arginine therapy.

PMID- 21088331
TI  - Exercise training in post-CABG patients at low prognostic risk. Beyond recovery
      from surgery.

PMID- 21088332
TI  - Is what you see in color intravascular ultrasound what you want to get?

PMID- 21088333
TI  - Gene mutations associated with atrioventricular block complicated by long QT
      syndrome.

PMID- 21088334
TI  - Does remodeling of gap junctions and connexin expression contribute to
      arrhythmogenesis? Study in an immobilization rat model.

PMID- 21088335
TI  - Metabolic syndrome and heart failure.

PMID- 21088336
TI  - Patients with chronic hepatitis C may be more sensitive to iron hepatotoxicity
      than patients with HFE-hemochromatosis.
AB  - AIM: In chronic hepatitis C, iron might play an important role as a hepatotoxic
      co-factor. Therefore, venesection, a standard treatment for hemochromatosis, has
      been proposed as an alternative for patients who respond poorly to anti-viral
      therapy. To improve our understanding of iron-induced hepatotoxicity, we compared
      the responses to venesection between patients with chronic hepatitis C and those
      with HFE-hemochromatosis. METHODS: Fourteen Japanese patients with chronic
      hepatitis C and eight Italian patients with HFE-hemochromatosis underwent
      repeated venesection with a serum ferritin endpoint of 20 and 50 ng/mL,
      respectively. Serum iron indices and liver function tests were measured in pre-
      and post treatment blood samples from each patient. Body iron stores were
      calculated using the removed blood volume. RESULTS: In both patients with
      hepatitis and hemochromatosis, serum ferritin, aminotransferase and hepcidin 25
      were reduced after venesection. The serum aminotransferase activity, but not the
      serum ferritin level, was predictive of effective iron removal treatment.
      Hepcidin regulation was set at an inappropriately low level in hemochromatosis
      patients (11.1 +/- 9.2 ng/mL), but not so in hepatitis patients (30.7 +/- 14.5
      ng/mL). Inversely, the estimated body iron stores of hemochromatosis patients
      were 5,960 +/- 2,750 mg, while those of hepatitis patients were 730 +/- 560 mg.
      Judging from the liver enzyme reduction ratio, patients with hepatitis seemed to
      be more sensitive to iron hepatotoxicity than hemochromatosis patients.
      CONCLUSION: Even though the threshold of iron hepatotoxicity and benefit of its
      removal differ between patients with chronic hepatitis C and those with HFE
      hemochromatosis, venesection is a valid choice of treatment to reduce liver
      disease activity in both diseases.

PMID- 21088337
TI  - Hemodialysis is an independent predictor of coronary in-stent restenosis after
      paclitaxel eluting stent implantation.
AB  - OBJECTIVE: A drug eluting stent is often used for high-risk patients with
      complications such as diabetes mellitus (DM) and hemodialysis (HD), however the
      factors to predict restenosis after paclitaxel-eluting stent (PES) placement have
      not been reported to date. METHODS: Between May 2007 and August 2009, 165
      consecutive patients (231 stents) received PES in our hospital. Stent diameter
      and length were determined by the use of intravascular ultrasound (IVUS). All
      patients continued to take 2 types of anti-platelet agents (aspirin and
      Clopidogrel or Ticlopidine). Ninety percent of the subjects received a follow-up
      coronary angiogram 6 months later. RESULTS: Underlying diseases were hypertension
      in 75%, hyperlipidemia in 78% and DM in 60% (15% on insulin), and 14% of the
      subjects received HD. Eighty-three percent of the patients had orally taken
      Statin, 85% ACE/ARB and 68% had beta blockers. Mean length and diameter of PES
      were 21.6 +/- 7.2 mm and 2.9 +/- 0.3 mm, respectively. Target lesion
      revascularization (TLR) rate 6 months after PES placement was 14.6% overall. In
      HD patients TLR was 43%, hypertension 15.0%, hyperlipemia 12.4%, DM with oral
      medication 12.5%, DM with insulin 12.0%, respectively. In multivariate analysis,
      HD was an independent risk factor for TLR (p=0.0001, OR: 6.61, 95% C.I.: 2.34
      18.6). CONCLUSION: HD had the greatest influence on TLR after PES even though
      risk factors were well controlled. It is necessary to develop new PCI techniques
      and stents that are useful for HD patients.

PMID- 21088338
TI  - Familial aggregation of lone atrial fibrillation in the Chinese population.
AB  - OBJECTIVE: Atrial fibrillation (AF) is the most common sustained cardiac
      arrhythmia associated with substantial morbidity and significant mortality. The
      familial aggregation of AF elsewhere in the world has been documented. This
      investigation sought to evaluate familial aggregation of lone AF in the Chinese
      population. METHODS: The study population included 382 unrelated patients with
      lone AF, and their 6,856 relatives. The controls were 15,507 age-sex-matched
      individuals from the general population. The prevalence of AF in each class of
      relatives was compared to that in each subgroup of the age- and sex- comparable
      control individuals. RESULTS: The relatives of patients with lone AF had a
      significantly increased risk of the arrhythmia as compared to the general
      population. The relative risk (95% confidence intervals) of AF for relatives
      compared to the general population was: 37.36 (12.71-109.9) for sons, 166.6
      (22.06-1258) for daughters, 27.39 (14.63-51.26) for brothers, 24.49 (14.01-42.83)
      for sisters, 4.87 (2.84-8.35) for mothers, and 4.78 (3.00-7.59) for fathers.
      CONCLUSION: These findings provide evidence suggesting that there is a
      significant familial aggregation of lone AF among Chinese families and a
      Mendelian genetic component involved in the pathogenesis of this prevalent
      disorder.

PMID- 21088339
TI  - Elevated levels of thioredoxin 1 in the lungs and sera of idiopathic pulmonary
      fibrosis, non-specific interstitial pneumonia and cryptogenic organizing
      pneumonia.
AB  - OBJECTIVE: Oxidant stress is thought to be involved in the establishment of
      idiopathic interstitial pneumonia (IIP). Thioredoxin 1 (TRX1) plays a role as a
      strong antioxidant in vivo, suggesting that TRX1 may be involved in the
      pathogenesis of IIPs. However, there is no report on TRX1 levels in the sera of
      IIPs. In addition, TRX1 expression in the lungs of non-specific interstitial
      pneumonia (NSIP) and cryptogenic organizing pneumonia (COP) patients also has not
      been reported. Here, we investigated whether or not TRX1 levels are altered in
      the lungs and sera of patients with idiopathic pulmonary fibrosis (IPF), NSIP,
      and COP. METHODS: Immunohistochemical analysis was performed to examine the
      expression of TRX1. TRX1 levels in sera were measured using an ELISA kit.
      RESULTS: TRX1 was expressed in the bronchiole-alveolar epithelium, especially
      with regenerative or metaplastic feature, and in alveolar macrophages in usual
      interstitial pneumonia (UIP) and fibrotic NSIP. TRX1 was weakly expressed in the
      lungs of cellular NSIP and COP. TRX1 producing cells in UIP (n=16), fibrotic NSIP
      (n=15), cellular NSIP (n=4), and COP (n=5) were significantly increased when
      compared to nonsmokers (n=7). TRX1 producing cells in UIP and fibrotic NSIP were
      significantly increased when compared to cellular NSIP and COP. TRX1 levels in
      the sera of the patients with IPF (n=32; 74.2 +/- 7.5 ng/mL), fibrotic NSIP (n=7;
      82.5 +/- 18.4 ng/mL), cellular NSIP (n=3; 62.2 +/- 3.2 ng/mL) and COP (n=17; 88.8
      +/- 19.7 ng/mL) were significantly higher than those of control subjects (n=74;
      35.3 +/- 2.7 ng/mL). Furthermore, TRX1 levels in the sera of IPF patients who
      later showed acute exacerbation (n=7; 106.6 +/- 16.3 ng/mL) were significantly
      higher than those of IPF patients without acute exacerbation (n=25; 65.1 +/- 7.6
      ng/mL). CONCLUSION: Overproduction of TRX1 in the lungs and sera may play an
      important role in the pathogenesis of IIPs.

PMID- 21088340
TI  - 24-hour recording of parkinsonian gait using a portable gait rhythmogram.
AB  - OBJECTIVE: In the advanced stage of Parkinson's disease (PD), motor fluctuation
      is a frequent and a disabling problem. Despite its importance, motor fluctuation
      has received little scientific analysis probably due to limitation in objective
      assessment. Here, we focused on gait disorders to estimate motor fluctuation in
      daily activities. PATIENTS AND METHODS: Using a new device, the portable gait
      rhythmogram, we recorded gait rhythm continuously over 24 hours in 22 patients
      with PD and in 11 normal controls, for quantitative evaluation of motor
      fluctuation. The duration of one gait cycle was measured. RESULTS: Continuous 24
      hour recording identified changes in gait rhythm, which correlated with
      fluctuation of PD symptoms. Different motor fluctuations were observed; a shift
      to a faster gait cycle was noted in patients with short-step walking, festination
      or freezing of gait, whereas a shift to a slower gait cycle was observed in
      patients with bradykinesia or instability. CONCLUSION: Characterization of motor
      fluctuation using this device could help in the selection of appropriate anti-PD
      medications.

PMID- 21088341
TI  - Prevalence of autosomal dominant cerebellar ataxia in Aomori, the northernmost
      prefecture of Honshu, Japan.
AB  - OBJECTIVE: The frequency of autosomal dominant cerebellar ataxia (ADCA) varies
      between different regions of Japan. This is the first report on the prevalence of
      ADCA subtypes in Aomori, Japan. METHODS AND PATIENTS: Sixty-five familial
      spinocerebellar ataxia (SCA) patients and 15 sporadic SCA patients were
      genetically examined. For only the SCA2 patients (n = 8), the magnetic resonance
      imaging (MRI) data were analyzed in detail. RESULTS: Spinocerebellar ataxia (SCA)
      type 6 was often observed (77.7% of cases), with SCA2 (10.6% of cases) being the
      next most common form. In contrast, only one of the eighty patients had SCA1.
      Among the 15 sporadic SCA patients, genetic mutations for SCA2, SCA6, SCA17, and
      SCA31 were identified, indicating that ADCAs should be considered in sporadic
      cases of ataxia. Furthermore, in SCA2 cases, brainstem atrophy, pontine midline
      linear hyperintensity, and atrophy of the frontal lobes were frequently observed
      using MRI. CONCLUSION: The present data indicate that the prevalence of ADCA in
      Aomori differs from other prefectures in the Tohoku District. MRI findings are
      very similar between SCA2 and multiple system atrophy (MSA), and thus care must
      be taken to prevent the misdiagnosis of sporadic SCA2 as MSA.

PMID- 21088342
TI  - Different clinical characteristics between polymicrobial and monomicrobial
      Aeromonas bacteremia--a study of 216 cases.
AB  - BACKGROUND: Part of Aeromonas bacteremia is polymicrobial infection. However, a
      clinical comparison of monomicrobial and polymicrobial Aeromonas bacteremia has
      not hitherto been reported. METHODS: A retrospective analysis of medical records
      of patients with Aeromonas bacteremia at three large referral hospitals in Taiwan
      for an 8-year period (2001-2008) was conducted. RESULTS: There were 154 patients
      with monomicrobial Aeromonas bacteremia and 62 patients with polymicrobial
      Aeromonas bacteremia. In the polymicrobial infections, E. coli was the most
      common combined pathogen (42%), followed by Klebsiella spp. (24%) and
      Enterobacter spp. (16%). Multivariate logistic regression analysis revealed solid
      cancer as the risk factor for polymicrobial Aeromonas bacteremia, with male
      gender and cirrhosis as risk factors for monomicrobial Aeromonas bacteremia.
      However, of all types of solid cancer, hepatoma was associated with monomicrobial
      Aeromonas bacteremia. APACHE II score was the most important prognostic factor in
      both groups. CONCLUSION: Aeromonas bacteremia in patients with cirrhosis or male
      gender tended to be monomicrobial. Polymicrobial Aeromonas bacteremia was
      associated with solid cancers. In either polymicrobial or monomicrobial Aeromonas
      bacteremia, prognosis could be predicted according to disease severity measured
      by APACHE II score.

PMID- 21088343
TI  - Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of
      acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Sivelestat is neutrophil elastase inhibitor, which is widely used
      in Japan for the treatment of acute lung injury. However, the clinical efficacy
      of the medication has not been convincingly demonstrated. METHODS: We conducted a
      systematic review and meta-analysis of randomized controlled trials on sivelestat
      for the treatment of acute lung injury and acute respiratory distress syndrome.
      Studies were identified using MEDLINE, EMBASE, Cochrane library, conference
      proceedings, and references of included studies. Authors were contacted if
      necessary. ICHUSHI, the Japanese database for medical literature and conference
      proceedings was also used for the search, since many studies on sivelestat were
      published in Japanese language and not registered in major databases such as
      MEDLINE. The primary outcome was mortality within 28-30 days after randomization.
      Relative risks were pooled with the random effect model. RESULTS: 8 trials were
      included in the analysis. There was no difference in mortality within 28-30 days
      after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26).
      Subgroup analysis conducted only on studies conducted in Japan showed the same
      result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation
      days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was
      associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56).
      Heterogeneity was not significant for the main analysis and funnel plot did not
      suggest publication bias. CONCLUSION: Sivelestat was not associated with
      decreased mortality, even when including studies published in Japanese language.

PMID- 21088344
TI  - Clinical and epidemiological features of Clostridium perfringens bacteremia: a
      review of 18 cases over 8 year-period in a tertiary care center in metropolitan
      Tokyo area in Japan.
AB  - OBJECTIVE: Clostridial sepsis has a very poor prognosis, owing to the life
      threatening combination of shock and acute massive hemolysis. No papers have
      described the clinical features of clostridial sepsis cases in Japan. Therefore,
      we retrospectively examined the clinical features of patients with systemic
      inflammatory response syndrome (SIRS) from whose blood cultures Clostridium
      perfringens was isolated. SUBJECTS AND MATERIALS: Blood samples were obtained
      from SIRS patients and cultured between January 1, 2001 and June 30, 2009. The
      samples were retrospectively reviewed, and 18 samples were positive for C.
      perfringens. The medical records of these 18 patients were reviewed for age,
      gender, underlying disease, past illnesses, results of physical and laboratory
      testing, and radiographic data. RESULTS: All patients were diagnosed with SIRS.
      Fifteen patients (83.3%) were >65 years old -mean age, 75+/-2 years (range, 59-88
      years). There were more men (13) than women (5). The blood cultures were obtained
      from patients in various wards: tertiary care center (8), emergency room (5),
      surgical ward (4), and medical ward (1). Hepatobiliary tract diseases such as
      gallbladder stones and hepatic carcinoma were the most frequent underlying
      diseases (8). Five patients died, resulting in an overall mortality rate at 30
      days of 27%. In the non-survival group, patients presented with septic shock (4)
      and gas-forming infection (2), and with significantly lower fibrinogen levels
      than those in the survival group. Septic shock at initial presentation was
      significantly associated with 30-day mortality for C. perfringens infection.
      DISCUSSION AND CONCLUSION: There were no specific characteristics among clinical
      features of C. perfringens infection accompanied with SIRS. This may indicate
      that, in emergency rooms, diagnosing and initiating appropriate treatment for C.
      perfringens infection may be considerably difficult. It is important to be
      especially vigilant in identifying patients with C. perfringens infection
      underlying SIRS, and accompanied by shock.

PMID- 21088345
TI  - Relation between serum Pro-Brain natriuretic peptide, myoglobin, CK levels and
      morbidity and mortality in high voltage electrical injuries.
AB  - OBJECTIVE: In our study, in addition to evaluating the relation between Pro-Brain
      natriuretic peptide (Pro-BNP), myoglobin and creatinine kinase (CK) levels and
      morbidity and mortality, we aimed at identifying the demographic characteristics
      of patients admited to emergency service after exposure to high electrical
      voltage. METHODS: In this prospective study, 48 emergency service patients
      exposed to high electric voltage were included; 19 healthy individuals were
      included as the control group. Their blood samples and electrocardiographies
      (ECG) were taken at the time of recourse upon their written approval. Demographic
      data and laboratory data were checked and compared among the patient group. We
      investigated the correlation between inpatients that had special clinical
      manifestations (escaratomy, fasciotomy, exitus, myoglobulinuria, third-degree
      burn, arrhythmia and etc.) and serum Pro-BNP, myoglobin and CK levels. RESULTS:
      When serum Pro-BNP, myoglobulin and CK levels were compared for the special
      clinical manifestations; the pro-BNP levels were statistically significantly
      higher in patients who had arrhythmia than in those without arrhythmia, and
      significantly higher in patients who died than in those who healed (respectively
      p=0.002 and p=0.007). In contrast, serum CK and myoglobin levels were not
      statistically significant. The serum CK and myoglobin levels were statistically
      significantly higher in patients who had third-degree burn than the others
      (p<0.001). CONCLUSION: Serum pro-BNP level is a marker that can be used for
      mortality and morbidity with patients exposed to high voltage electrical
      injuries.

PMID- 21088346
TI  - Guillain-Barre syndrome after streptokinase therapy for acute myocardial
      infarction.
AB  - Some drugs including streptokinase have been reported to precipitate Guillain
      Barre syndrome. We report a 70-year-old man with acute anterior myocardial
      infarction who developed Guillain-Barre syndrome seven days after thrombolytic
      therapy with streptokinase.

PMID- 21088347
TI  - A case of early carcinoma of the papilla of Vater confined to the mucosa and
      continuative epithelium of glands in Oddi's sphincter (m-God) treated by
      endoscopic papillectomy.
AB  - We herein report a case of early stage ampullary cancer, treated by endoscopic
      papillectomy, in which tumor extension was confined to the mucosa and adjacent
      epithelium of the glands in Oddi's sphincter. A 77-year-old man underwent
      screening esophagogastroduodenoscopy, which revealed a mass in the papilla of
      Vater, which was well-differentiated adenocarcinoma as proven by biopsy. The
      tumor was diagnosed as T1 and endoscopic papillectomy was performed. Histological
      examination showed adenocarcinoma limited to the mucosa of the common channel and
      continuative epithelium of the neighboring glands in Oddi's sphincter. No signs
      of recurrence have been observed during a follow-up of 23 months.

PMID- 21088348
TI  - Left main coronary artery thrombosis complicating an idiopathic retroperitoneal
      fibrosis in a 37-year-old man with long-standing type I diabetes mellitus.
AB  - Retroperitoneal fibrosis is an uncommon collagen vascular disease of unknown
      etiology, characterized by the replacement of normal retroperitoneal tissue with
      fibrosis and/or chronic inflammation usually surrounding the abdominal aorta and
      the iliac arteries and extending into adjacent anatomic structures. No cases of
      acute coronary syndrome in the setting of retroperitoneal disorder have been
      published as yet. We report a 37-year-old man with a 14-year history of type I
      diabetes mellitus who was admitted to the endocrinology department for a routine
      check up and glycemic re-equilibration and who was later diagnosed to have an
      idiopathic retroperitoneal fibrosis. The patient presented during his
      hospitalisation with a non ST elevation myocardial infarction caused by an
      isolated thrombus located inside the left main coronary artery successfully
      treated with manual thrombectomy.

PMID- 21088349
TI  - Successful blood pressure control with additive administration of eplerenone, an
      aldosterone receptor blocker, in a patient with bilateral renovascular
      hypertension treated with angioplasty.
AB  - A 29-year-old woman with refractory hypertension who previously suffered from
      subarchnoid hemorrhage visited our facility. The diagnosis of renovascular
      hypertension due to fibromuscular dysplasia was made based on a high level of
      plasma renin activity (PRA) and aldosterone concentration (AC), and computed
      tomographic image of bilateral renal artery stenosis/obstruction. Angioplasty,
      which could be performed only to the left renal artery, failed to regain
      sufficient BP control. The addition of eplerenone, an aldosterone receptor
      blocker, to the conventional antihypertensive drugs successfully and safely
      lowered BP and preserved the renal function despite the persistence of high PRA
      and AC values.

PMID- 21088350
TI  - Rapidly progressing aneurysm of infected thoracic aorta with pseudoaneurysm
      formation.
AB  - A 60-year-old man presented with chest discomfort with fever and high C-reactive
      protein (CRP). Chest computed tomography (CT) disclosed a mediastinal soft tissue
      swelling originating from the aortic arch, and gallium-67 single-photon emission
      CT revealed intense uptake in the same region. We initially suspected
      mediastinitis and/or a thoracic aortic infection. Antibiotics improved his
      symptoms and CRP levels. However, a follow-up CT scan 33 days later, revealed an
      aortic arch aneurysm and the patient was diagnosed with infective aortic
      aneurysm. Here, we report a rare case of a rapidly progressing aneurysm of
      infected aorta aortic infection with pseudoaneurysm formation.

PMID- 21088351
TI  - A case of adolescent hyperlipoproteinemia with xanthoma and acute pancreatitis,
      associated with decreased activities of lipoprotein lipase and hepatic
      triglyceride lipase.
AB  - Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) enhance the
      hydrolysis of triglycerides (TG) transported by chylomicron (CM) and very-low
      density lipoprotein (VLDL). We report a case of severe hyperchylomicronemia with
      high levels of remnant lipoprotein and total cholesterol (T-Chol) in a 15-year
      old boy. Precise examination of the lipid profile showed decreased activities of
      both LPL and HTGL, although the protein mass for LPL and HTGL were maintained. In
      addition, bezafibrate treatment effectively ameliorated hypertriglyceridemia in
      this case. This is the first case of hyperchylomicronemia with decreased
      activities and unaffected protein masses for both LPL and HTGL, without overt
      immuno-dysfunction.

PMID- 21088352
TI  - Colon perforation as a critical complication of exertional heat stroke.
AB  - Although reduced intestinal blood flow causing barrier dysfunction and
      endotoxemia is well documented in the pathogenesis of heat stroke (HS),
      complications of the gastrointestinal tract are less appreciated in HS patients.
      Herein, we report the case of a young man with exertional HS complicated with
      colon perforation. Acute abdomen, bloody diarrhea, dilated bowel loop, and
      unexplained shock should be considered as warning signs of colonic ischemia and
      consequent perforation. Early recognition is the key factor for improving the
      outcome of HS patients complicated with colon perforation.

PMID- 21088353
TI  - Absence of hypoalbuminemia despite nephrotic proteinuria in focal segmental
      glomerulosclerosis secondary to polycythemia vera.
AB  - In addition to displaying geographic variation, focal segmental
      glomerulosclerosis (FSGS) has become the commonest cause of the nephrotic
      syndrome seen in adults in recent years. Secondary FSGS in particular, is
      observed when glomerular workload is increased. Polycythemia vera (PV) is a
      hematological disease characterized by abnormal proliferation in the erythroid
      series. The number of case reports belonging to glomerulonephritis secondary to
      PV is limited. In the literature, there are few reports of FSGS. One study
      pointed out that the presence of normoalbuminemia was detected in patients with
      FSGS secondary to hyperfiltration when there was nephrotic proteinuria. Here, we
      report a case of FSGS following a course with normoalbuminemia despite nephrotic
      range proteinuria developing secondary to PV. Our case is the first report in the
      literature with thes characteristics.

PMID- 21088354
TI  - Pleuritis caused by Campylobacter jejuni subspecies jejuni in a patient
      undergoing long-term hemodialysis.
AB  - A 73-year-old female hemodialysis patient experienced fever, shortness of breath
      on effort, and chest discomfort. A decrease in breath sounds in the right lung
      field, leukocytosis, elevated CRP level, and a right massive pleural effusion
      were observed. The patient was diagnosed with bacterial pleuritis based on
      leukocyte-predominant exudative pleural effusion, and treated with ceftriaxone.
      Her symptoms, however, were not improved, so thoracic drainage was attempted.
      Campylobacter species were isolated from cultured pleural fluid samples, and
      Campylobacter jejuni subspecies jejuni was detected on the multiplex PCR assay.
      The antibiotic was therefore changed to minocycline following pazufloxacin, and
      her symptoms were improved.

PMID- 21088355
TI  - Juvenile pulmonary hypertension associated with fibromuscular dysplasia.
AB  - A 20-year-old female diagnosed as idiopathic pulmonary arterial hypertension at 7
      years of age was referred with worsening dyspnea and chest pain. Several imaging
      studies and right cardiac catheterization showed multiple stenoses in the
      peripheral pulmonary arteries with severe pulmonary hypertension and multiple
      systemic arterial stenoses lacking in systemic hypertension. No evidence of
      inflammatory or autoimmune disease was detected. Fibromuscular dysplasia was
      clinically diagnosed because of the narrowed systemic and pulmonary arterial
      stenoses which included dilatation and aneurysms that appeared similar to a
      string of beads. Treatment with sildenafil yielded a temporary improvement in her
      disease state.

PMID- 21088356
TI  - Spinal myeloid sarcoma in two non-leukemic patients.
AB  - Myeloid sarcoma, formerly termed granulocytic sarcoma or chloroma, consists of
      neoplastic granulocytic precursors and myeloblasts. Isolated chloromas
      (granulocytic sarcomas) are rare tumors. Spinal complications of chloromas, such
      as cord compression secondary to epidural tumor or cauda equine syndrome have
      been described but are rare. We herein report two cases with spinal granulocytic
      sarcomas in non-leukemic patients. The case of a previously healthy 22-year-old
      man diagnosed with multiple spinal granulocytic sarcomas with no evidence of bone
      marrow or other hematological involvement is described. And, a 43-year-old woman
      diagnosed cervical spinal granulocytic sarcoma with no evidence of bone marrow or
      other hematological involvement is described. The tumor was totally removed by
      microsurgery. The histopathological examination was consistent with granulocytic
      sarcoma. Granulocytic sarcoma should be considered in the differential diagnosis
      of an epidural mass in patients with or without acute leukemia, because early
      diagnosis followed by appropriate combined chemotherapy and radiation may obviate
      surgical intervention and eventually prevent leukemic transformation.

PMID- 21088357
TI  - Successful treatment of systemic Geotrichum capitatum infection by liposomal
      amphotericin-B, itraconazole, and voriconazole in a Japanese man.
AB  - Severe systemic Geotrichum capitatum (G. capitatum) infection is rare, especially
      in Japan. G. capitatum infection has been reported mainly in immunocompromised
      patients and the prognosis is poor with a mortality rate of approximately 50-75%.
      Here, we report a Japanese case of systemic G. capitatum infection in a severe
      neutropenic patient who was receiving chemotherapy for acute myelogeneous
      leukemia with multilineage dysplasia. G. capitatum was isolated from blood
      cultures, and also formed multiple nodular lesions in lung fields. The infection
      was successfully cured with a combination of amphotericin B, itraconazole, and
      voriconazole.

PMID- 21088358
TI  - L-asparaginase-induced complete response in a relapsed patient with Epstein-Barr
      virus and cytotoxic peripheral T-cell lymphoma not otherwise specified.
AB  - We present a patient with Epstein-Barr virus (EBV)-positive cytotoxic peripheral
      T-cell lymphoma, not otherwise specified (PTCL-NOS) who was successfully treated
      using only L-asparaginase. A 46-year-old Japanese man was diagnosed with EBV
      positive cytotoxic PTCL-NOS. Although he underwent chemotherapy using multiple
      agents, he relapsed with hemophagocytic syndrome. L-asparaginase treatment was
      initiated at 6,000 U/m(2) on days 1, 3, 5, 10, and 12 together with prednisolone
      at 1 mg/kg. Although he developed grade 2 liver dysfunction and grade 2
      coagulopathy, the patient achieved complete response status. Finally, he
      underwent allogeneic bone marrow stem cell transplantation, and he is currently
      still alive without disease at 24 months after the start of L-asparaginase
      therapy.

PMID- 21088359
TI  - Mefloquine treatment in a patient suffering from progressive multifocal
      leukoencephalopathy after umbilical cord blood transplant.
AB  - We report herein the case of a 37-year-old man who developed probable progressive
      multifocal leukoencephalopathy (PML) following an umbilical cord blood
      transplant. The patient showed favorable clinical, neuroradiological and
      virological responses after treatment with mefloquine, an anti-malarial drug.
      Mefloquine may offer some benefits as a treatment for PML in patients with or
      without human immunodeficiency virus type-1 infection. This report highlights the
      need to gather sufficient data to confirm the efficacy of mefloquine against this
      devastating viral disease of the central nervous system.

PMID- 21088360
TI  - Diphenylhydantoin-induced severe yet reversible anemia during pregnancy.
AB  - Diphenylhydantoin (DPH) therapy, often used in treating epileptic seizures, can
      cause anemia in some patients. A 26-year-old female suffered from convulsions due
      to encephalitis and was placed on DPH therapy. About two months after the
      initiation of DPH therapy, her hemoglobin level was 3.8 g/dL. Her anemia improved
      after the discontinuation of DPH, confirming that the anemia was caused by DPH.
      Pure red-cell aplasia (PRCA) combined with hemolytic anemia was indicated by
      results such as erythroid aplasia, an increased LDH level, and a decreased
      haptoglobin level. PRCA complicated by hemolytic anemia could be responsible for
      anemia associated with DPH.

PMID- 21088361
TI  - Pedunculated leiomyomatous polyp (pedunculated leiomyoma) of the transverse
      colon.

PMID- 21088362
TI  - Torsades de pointes mimicking monomorphic ventricular tachycardia.

PMID- 21088363
TI  - Computed tomographic demonstration of an acquired aortopulmonary fistula.

PMID- 21088364
TI  - Ectopic (pelvic) autosomal dominant polycystic kidney disease.

PMID- 21088365
TI  - Association of primary myeloperoxidase deficiency and myeloproliferative
      neoplasm.

PMID- 21088366
TI  - Monoparesis of the leg caused by parasagittal meningioma.

PMID- 21088367
TI  - Successful interferon-alpha treatment in a patient with IgA nephropathy
      associated with hepatitis C virus infection.

PMID- 21088368
TI  - Recent progress in antithrombotic therapy for atrial fibrillation.
AB  - Atrial fibrillation (AF) is becoming a major health care burden as elderly
      populations increase. The increased risk of stroke and thromboembolisms in
      patients with AF is well documented and anti-coagulation with adjusted-dose
      warfarin is highly effective in reducing stroke risk, being superior to
      antiplatelet agents. Despite recognition of the epidemiological problem and the
      sound evidence base for thromboprophylaxis, as well as major guidelines
      recommending treatment, anticoagulation use is still suboptimal, given the dis
      utility and limitations associated with warfarin. Recent developments in
      thromboprophylaxis for AF include efforts for better risk stratification for
      predictions of thromboembolic risk. Constant efforts are underway to develop
      newer, less cumbersome, alternatives to warfarin with similar (or better)
      efficacy. This review article provides an overview of the recent progress made,
      the potential challenges involved and the future of these therapeutic approaches.

PMID- 21088369
TI  - Association and prognostic impact of heart rate and micro- albuminuria in
      patients with type 2 diabetes and cardiovascular disease: results from the
      PROactive trial.
AB  - AIM: Microalbuminuria (MAU) and heart rate are established predictors of an
      adverse cardiovascular outcome. Recently, heart rate was described as an
      independent predictor of MAU in hypertensive patients, raising the question of a
      causal link. METHODS: In post-hoc analysis of the PROactive trial we examined the
      association of the baseline heart rate and MAU in diabetic patients with
      cardiovascular disease (n = 5,110, mean age 62 +/- 8, 66% male) using logistic
      regression. Cox regression analysis was used to examine the independent impact of
      heart rate and MAU on the composite endpoint of all-cause mortality, myocardial
      infarction and stroke. RESULTS: Baseline heart rate was not associated with a
      significantly increased risk for MAU at baseline (OR 1.01 per 10 bpm, 95% CI 0.97
      1.06, p = 0.48) or MAU at the final visit (OR per 10 bpm 1.04, 95% CI 0.98-1.11,
      p = 0.20). Similar results were observed in subgroups of patients with
      hypertensive blood pressure at baseline (OR 0.98 per 10 bpm, 95% CI 0.93-1.03, p
      = 0.42) or patients with a history of hypertension (OR 1.02 per 10 bpm, 95% CI
      0.98-1.07, p = 0.31), respectively. Stratification by use of an ACE inhibitor/AT1
      receptor blocker did also not change the results. In multivariate analysis, both
      heart rate and MAU were significantly predictive of a cardiovascular outcome.
      CONCLUSION: There was no evidence of an association between heart rate and MAU in
      diabetic patients with cardiovascular disease, independently of whether
      hypertension was present or not, but both markers were independently predictive
      of a cardiovascular outcome. These results do not support a causal link between
      heart rate and MAU.

PMID- 21088370
TI  - Smoking during pregnancy increases risks of various obstetric complications: a
      case-cohort study of the Japan Perinatal Registry Network database.
AB  - BACKGROUND: The adverse effects of maternal smoking on the health of pregnant
      women have been examined mostly on a disease-by-disease basis. The aims of this
      study were to evaluate simultaneously the effects of smoking during pregnancy on
      various obstetric complications, using data from a large medical database, and to
      investigate the expediency of using a case-cohort design for such an analysis.
      METHODS: A case-cohort study was conducted within the Japan Perinatal Registry
      Network database. Perinatal information on infant deliveries was entered into the
      database at 125 medical centers in Japan. The base population of the study was
      180 855 pregnant women registered in the database from 2001 through 2005. The
      outcome measures were the incidences of 11 different obstetric complications.
      Logistic regression models were used to estimate age-adjusted risk ratios (aRRs)
      and relative excess incidence proportions (REIs). RESULTS: The overall prevalence
      of smoking during pregnancy was 5.8% in the base cohort, and the prevalence was
      higher among younger women. A comparison of the cases and control cohort showed
      that smokers during pregnancy had statistically significant higher risks for
      preterm rupture of the membrane (aRR: 1.67, 95% confidence interval [CI]: 1.43
      1.96; REI: 40.2%, 95% CI: 29.9%-49.1%), chorioamnionitis (1.65, 1.36-2.00; 39.4%,
      26.4%-50.0%), incompetent cervix (1.63, 1.35-1.96; 38.5%, 25.8%-49.1%),
      threatened premature delivery (1.38, 1.17-1.64; 27.7%, 14.5%-38.9%), placental
      abruption (1.37, 1.10-1.72; 27.1%, 8.8%-41.7%), and pregnancy-induced
      hypertension (1.20, 1.01-1.41; 16.4%, 1.2%-29.3%). CONCLUSIONS: Maternal smoking
      was associated with a number of obstetric complications. This highlights the
      importance of smoking cessation during pregnancy. In addition, case-cohort
      analysis proved useful in estimating RRs for multiple outcomes in a large
      database.

PMID- 21088371
TI  - Avoidance and inhibition do not predict nonrespondent bias among patients with
      inflammatory bowel disease.
AB  - BACKGROUND: It has been suggested that participant withdrawal from studies can
      bias estimates. However, this is only possible when withdrawers and
      nonwithdrawers differ in an important way. We tested the hypothesis that
      withdrawers are more likely than nonwithdrawers to be avoidant and negatively
      affected. METHODS: A total of 1160 participants with inflammatory bowel disease
      were recruited at different sites in Switzerland. Their levels of avoidance
      coping and negative affectivity were rated by means of 2 short baseline
      questionnaires. One year later, they were sent a longer follow-up questionnaire.
      The primary outcome was return versus non-return of the follow-up questionnaire
      within 3 months. After controlling for potential confounders identified in an
      extensive literature search, we estimated the odds of returning the follow-up
      questionnaire for 1 standard deviation of avoidance coping and negative
      affectivity. RESULTS: The odds ratio for 1 standard deviation was 1.03 (95%
      confidence interval: 0.89-1.18) for avoidance coping and 1.02 (0.89-1.17) for
      negative affectivity. CONCLUSIONS: The odds of returning the questionnaires did
      not depend on avoidance coping or negative affectivity.

PMID- 21088372
TI  - Time series analysis of incidence data of influenza in Japan.
AB  - BACKGROUND: Much effort has been expended on interpreting the mechanism of
      influenza epidemics, so as to better predict them. In addition to the obvious
      annual cycle of influenza epidemics, longer-term incidence patterns are present.
      These so-called interepidemic periods have long been a focus of epidemiology.
      However, there has been less investigation of the interepidemic period of
      influenza epidemics. In the present study, we used spectral analysis of influenza
      morbidity records to indentify the interepidemic period of influenza epidemics in
      Japan. METHODS: We used time series data of the monthly incidence of influenza in
      Japan from January 1948 through December 1998. To evaluate the incidence data, we
      conducted maximum entropy method (MEM) spectral analysis, which is useful in
      investigating the periodicities of shorter time series, such as that of the
      incidence data used in the present study. We also conducted a segment time series
      analysis and obtained a 3-dimensional spectral array. RESULTS: Based on the
      results of power spectral density (PSD) obtained from MEM spectral analysis, we
      identified 3 periodic modes as the interepidemic periods of the incidence data.
      Segment time series analysis revealed that the amount of amplitude of the
      interepidemic periods increased during the occurrence of influenza pandemics and
      decreased when vaccine programs were introduced. CONCLUSIONS: The findings
      suggest that the temporal behavior of the interepidemic periods of influenza
      epidemics is correlated with the magnitude of cross-reactive immune responses.

PMID- 21088373
TI  - Isolated renal artery thrombosis because of blunt trauma abdomen: report of a
      case with review of the literature.
AB  - BACKGROUND: Isolated renal trauma in case of blunt trauma abdomen (BTA) is not
      common. Renal artery occlusion by thrombosis in such cases is seen very rarely.
      These cases had been traditionally treated by early nephrectomy, but nowadays,
      renal preservation is considered whenever possible. Treatment options to do so
      are being developed. METHODS: Recently we came across one such case of isolated
      unilateral renal artery thrombosis (RAT) because of BTA. Relevant literature
      especially on various therapeutic techniques has been critically reviewed briefly
      along with case presentation. RESULTS: Isolated blunt traumatic RAT has an
      incidence of less than 1%. Only about 400 cases have been reported. It must be
      diagnosed and treated as soon as possible to avoid progressive permanent loss of
      renal function. Contrast-enhanced CT scanning is the preferred modality for
      evaluation and follow-up of RAT. Conservative treatment is reserved for
      unilateral cases. For bilateral cases and when RAT occurs in a solitary kidney,
      revascularization either surgically or more preferably by less invasive
      percutaneous techniques has been recommended. CONCLUSION: Renal arterial
      thrombosis because of blunt abdominal trauma is still an underreported entity,
      treatment for which has not yet been established. Both early nephrectomy and
      delayed revascularization are not justified treatment options.

PMID- 21088374
TI  - Sex and the frontal cortex: A developmental CT study in the spotted hyena.
AB  - The purpose of this study was to examine developmental and individual variation
      in total endocranial volume and regional brain volumes, including the anterior
      cerebrum, posterior cerebrum and cerebellum/brain stem, in the spotted hyena
      (Crocuta crocuta). The spotted hyena is a highly gregarious animal noted for
      living in large, hierarchically organized groups. The social lives of male and
      female spotted hyenas do not differ until after puberty, when males disperse from
      the natal group, while females remain philopatric. Here we sought to determine
      whether the divergent life histories of male and female spotted hyenas are linked
      to differences in brain size or organization. Three-dimensional virtual endocasts
      were created using computed tomography from 46 spotted hyenas skulls (23 females,
      22 males, 1 unknown sex) ranging in age from 1 day to 18 years. Brain volume and
      skull length were highly correlated (r = 0.91), and both reached asymptotic
      values by 34 months of age. Analyses of total endocranial volume (relative to
      skull length) and cerebellum/brain stem volume (relative to total endocranial
      volume) revealed no sex differences. However, relative anterior cerebrum volume,
      comprised mainly of frontal cortex, was significantly greater in adult males than
      adult females, and relative posterior cerebrum volume was greater in adult
      females than adult males. We hypothesize that the demands of neural processing
      underlying enhanced social cognition required for successful male transfer
      between matriarchical social groups at dispersal may be greater than cognitive
      demands on philopatric females.

PMID- 21088375
TI  - Imaging of fetal cytomegalovirus infection.
AB  - Fetuses with congenital cytomegalovirus infection may remain asymptomatic or
      present with a wide range of brain pathologies. These findings are not always
      obvious but may on some occasions be demonstrated by ultrasound and MRI, they
      include ventriculomegaly, microcephaly, increased periventricular echogenicity,
      calcifications, periventricular pseudocysts, intraventricular synechia,
      malformations of cortical development, cerebellar lesions and T2 abnormal
      temporal signals. The purpose of this mini-review is to describe US and MRI
      findings characteristic of congenital cytomegalovirus infection, with particular
      emphasis on their time of appearance, frequency and specificity.

PMID- 21088377
TI  - Clusterin immunoreactivity as a predictive factor for progression of non-muscle
      invasive bladder carcinoma.
AB  - INTRODUCTION: There is a need for prognostic markers which can predict the subset
      of patients who will not respond sufficiently to conservative management in non
      muscle-invasive bladder carcinoma. We analyzed the association of clusterin (CLU)
      with clinicopathological factors. MATERIALS AND METHODS: Immunohistochemical CLU
      expression was investigated in paraffin-embedded archival tissues of initial
      transurethral resection specimens of 46 patients with non-muscle-invasive bladder
      carcinoma. The result was expressed as the proportion of the number of CLU
      containing tumor cells to the total number of tumor cells detected in each slide
      and 'percent CLU expression' was calculated for each patient. RESULTS: Of the 46
      cases (35 male, 11 female), 18 were >= 65 years of age. CLU expression was
      significantly higher in male and elderly patients. Following the initial
      transurethral resection, 39 patients showed tumor recurrence, and progression was
      seen in 25 patients, of whom 17 progressed to muscle invasion during follow-up.
      Although there was no significant correlation between CLU expression and
      recurrence, significant correlation with overall progression and progression to
      muscle-invasive disease was observed in this cohort of patients (p = 0.001 and p
      = 0.014, respectively). Among the patients with progression to muscle invasion,
      13 underwent radical cystectomy with pT2 tumor in 5 patients in the final
      pathology of surgical specimens and pT3 and higher in the remainder. CONCLUSIONS:
      CLU immunoreactivity showed correlation with age, gender and progression, mainly
      progression to muscle invasion. Thus, CLU can be used as a molecular marker to
      predict the potential of progression to muscle-invasive disease in a particular
      tumor which in turn may prove useful in the decision-making process for early
      cystectomy without losing time with conservative management.

PMID- 21088378
TI  - The nature of neuroethology.

PMID- 21088376
TI  - Priming of neutrophils and differentiated PLB-985 cells by pathophysiological
      concentrations of TNF-alpha is partially oxygen dependent.
AB  - Activation of polymorphonuclear leukocytes (PMN) can be modulated to intermediate
      'primed' states characterized by enhanced responsiveness to subsequent stimuli.
      We studied priming in response to TNF-alpha in human PMN and PLB-985 cells, a
      myeloid cell line differentiated to a neutrophilic phenotype (PLB-D). PMN
      generated reactive oxygen species (ROS) in response to TNF-alpha alone, and NADPH
      oxidase activity increased in response to stimulation with formyl-Met-Leu-Phe
      after priming. PLB-D cells also demonstrated priming of NADPH oxidase activity.
      Similar to priming by endotoxin, priming of the respiratory burst by TNF-alpha
      was predominantly oxygen dependent, with marked attenuation of ROS generation if
      primed anaerobically. Both PMN and PLB-D cells displayed significant increases in
      cell surface CD11b and gp91(phox) expression after TNF-alpha priming and PMN
      displayed activation of MAPK. In response to TNF-alpha priming, neither
      mobilization of intracellular proteins nor activation of MAPK pathways was NADPH
      oxidase dependent. Priming of PMN and PLB-D cells by low TNF-alpha concentrations
      enhanced chemotaxis. These data demonstrate that pathophysiological
      concentrations of TNF-alpha elicit NADPH oxidase-derived ROS and prime cells for
      enhanced surface protein expression, activation of p38 and ERK1/2 MAPK pathways,
      and increased chemotaxis. Furthermore, PLB-D cells undergo TNF-alpha priming and
      provide a genetically modifiable model to study priming mechanisms.

PMID- 21088379
TI  - The Karyology of Uraeotyphlus gansi, and Its Implications for the Systematics and
      Evolution of Uraeotyphlidae (Amphibia: Gymnophiona).
AB  - The gross karyotype of the uraeotyphlid caecilian Uraeotyphlus gansi is described
      as comprising 2n = 42 and fundamental number = 58. These are the first karyotype
      data for any species of malabaricus-group Uraeotyphlus, and the diploid number is
      the same as those ichthyophiids thus far studied and differs from the oxyurus
      group Uraeotyphlus (2n = 36). These data support the recognition of two species
      groups within Uraeotyphlus, the monophyly of the oxyurus group, and the
      understanding that the ancestral diatriatan was more ichthyophiid- than
      uraeotyphlid-like.

PMID- 21088380
TI  - Identification of new susceptibility regions for X;Y translocations in patients
      with testicular disorder of sex development.
AB  - Testicular disorder of sex development in the presence of a 46,XX karyotype is a
      rare condition. In most instances, it is caused by an X;Y translocation in the
      paternal gametes, causing SRY to be transferred on the X chromosome. An abnormal
      recombination event between homologous genes PRKX and PRKY is implicated in
      approximately one third of the cases. In this study, we report the
      characterization by fluorescence in situ hybridization of four patients with a
      46,X,der(X)t(X;Y) constitution: two monozygotic adult twins, one adult male and a
      young boy. Molecular cytogenetic analyses using BAC clones specific to the X and
      Y chromosomes revealed that the translocation is not mediated by an abnormal PRKX
      PRKY recombination event in any of our patients. On the other hand, the twins and
      the adult male have similar breakpoints, having almost the entire short arm of
      the Y chromosome translocated on their der(X). On their der(X) chromosome,
      breakpoints are located close to PRKX, in an interval of less than 200 kb. As for
      the young boy, his breakpoints are located approximately 300 kb proximal to SRY,
      in Yp11.31, and at the beginning of the pseudoautosomal region in Xp22.33. Our
      data suggest that some regions are prone to breakage on the sex chromosomes and
      that these regions represent possible hot spots for X;Y translocations that are
      not mediated by abnormal recombination.

PMID- 21088381
TI  - Male fertility, chromosome abnormalities, and nuclear organization.
AB  - Numerous studies have implicated the role of gross genomic rearrangements in male
      infertility, e.g., constitutional aneuploidy, translocations, inversions, Y
      chromosome deletions, elevated sperm disomy, and DNA damage. The primary purpose
      of this paper is to review male fertility studies associated with such
      abnormalities. In addition, we speculate whether altered nuclear organization,
      another chromosomal/whole genome-associated phenomenon, is also concomitant with
      male factor infertility. Nuclear organization has been studied in a range of
      systems and implicated in several diseases. For many applications the measurement
      of the relative position of chromosome territories is sufficient to determine
      patterns of nuclear organization. Initial evidence has suggested that, unlike in
      the more usual 'size-related' or 'gene density-related' models, mammalian
      (including human) sperm heads display a highly organized pattern including a
      chromocenter with the centromeres located to the center of the nucleus and the
      telomeres near the periphery. More recent evidence, however, suggests there may
      be size- and gene density-related components to nuclear organization in sperm. It
      seems reasonable to hypothesize therefore that alterations in this pattern may be
      associated with male factor infertility. A small handful of studies have
      addressed this issue; however, to date it remains an exciting avenue for future
      research with possible implications for diagnosis and therapy.

PMID- 21088382
TI  - Aminoguanidine improves epididymal sperm parameters in varicocelized rats.
AB  - INTRODUCTION: Increased levels of nitric oxide (NO) in the spermatic veins of men
      affected by varicocele have already been reported. But there is no study to
      discriminate the subtype of catalytic enzyme for synthesis of NO. In this study,
      aminoguanidine (AG), an inducible NO synthase inhibitor, has been used to
      investigate its effect on sperm parameters. METHODS: Twenty-four male Wistar rats
      were divided into four groups. In groups A and B, left experimental varicocele
      was induced by a 20-gauge needle. Group C (sham) underwent a similar procedure to
      groups A and B, but the spermatic vein was left intact, and group D served as
      control group. The animals in group A were killed 10 weeks later and their sperm
      count, motility, morphology and vitality were evaluated. Group B received 50
      mg/kg AG with i.p. injection daily for 10 weeks. RESULTS: Sperm count, motility,
      morphology and vitality were significantly decreased in group A in comparison to
      control group (p <= 0.05). In group B, sperm parameters improved in comparison to
      group A (p <= 0.01). Group C did not show any significant alterations in sperm
      parameters compared with control group. CONCLUSION: These findings may support
      the concept that AG can improve the sperm count, motility, morphology and
      vitality in infertile rats with varicocele.

PMID- 21088384
TI  - Epigenetic control of estrogen receptor expression and tumor suppressor genes is
      modulated by bioactive food compounds.
AB  - BACKGROUND: The tumor suppressor genes p15(INK)4(b) and p16(INK)4(a) as well as
      the estrogen receptor-alpha (ESR1) gene are abnormally methylated and expressed
      in colon cancer. The cancer-preventative abilities of several bioactive food
      components have been linked to their estrogenic and epigenetic activities.
      METHODS: The effect of folic acid, zebularine, resveratrol, genistein and
      epigallocatechin-3-gallate (EGCG) on tumor cell growth, promoter methylation of
      ESR1, p15(INK)4(b) and p16(INK)4(a) and gene expression of ESR1 and ESR2 was
      analyzed in Caco-2 cells. Gene expression was measured using real-time PCR, and
      promoter CpG methylation was assessed using bisulfite conversion and methylation
      specific PCR. RESULTS: After exposure to a high concentration of folic acid (20
      MUmol/l), enhanced cancer cell growth and concomitant increased methylation of
      the ESR1 (3.6-fold), p16(INK)4(a) and p15(INK)4(b) promoters was observed. A
      lower concentration of folic acid (2 MUmol/l) decreased cell growth. The
      phytoestrogens genistein and resveratrol enhanced expression of ESR1 (genistein
      200 MUmol/l: 2.1-fold; resveratrol 50 MUmol/l: 6.3-fold) and ESR2 (2.6- and 3.6
      fold, respectively). Genistein and resveratrol treatment increased promoter
      methylation of ESR1 (genistein 200 MUmol/l: 2.9-fold; resveratrol 50 MUmol/l: 1.4
      fold). For p16(INK)4(a), increased methylation was found after exposure to 10
      MUmol/l resveratrol, but for p15(INK)4(b), decreased methylation was found. Both
      components showed growth-inhibitory activities. For EGCG, growth inhibition at
      100 MUmol/l and suppressed promoter methylation of tumor suppressor genes
      (p16(INK)4(a): 0.9-fold; p15(INK)4(b): 0.6-fold) was seen. CONCLUSIONS: Our
      results show that these food compounds regulate ESR and tumor suppressor gene
      expression by multiple mechanisms including epigenetic processes. An improved
      understanding of these epigenetic effects could therefore support specific
      dietary concepts of epigenetic cancer prevention and intervention.

PMID- 21088383
TI  - Effect of antioxidant vitamins on the plasma homocysteine level in a free-living
      elderly population.
AB  - BACKGROUND: The factors influencing total plasma homocysteine levels (tHcy) are
      of special interest in the attempt to reduce cardiovascular risk. AIM: This
      investigation aimed to assess the independent effects of antioxidant vitamins on
      tHcy in elderly people. METHODS: Our cross-sectional analysis included data of
      184 subjects (>=60 years) from the longitudinal study in an aging population in
      Giessen (GISELA), Germany. We examined the effects of plasma levels, intake and
      supplementation of vitamin C, vitamin E, and beta-carotene on tHcy. RESULTS: The
      mean tHcy was within the normal range in this population. Serum folate, the
      estimated glomerular filtration rate (eGFR), and plasma vitamin C showed a
      negative association with tHcy in simple regression analysis. In a subsequent
      multiple regression analysis, eGFR, serum folate, and plasma vitamin C were the
      relevant independent predictors of tHcy. Intake and supplementation of vitamin C,
      as well as plasma levels, intake and supplementation of vitamin E, and beta
      carotene were not associated with tHcy. CONCLUSION: Vitamin C may be an
      independent predictor of tHcy in free-living elderly people and, therefore,
      should be considered in attempts to reduce tHcy.

PMID- 21088385
TI  - Hypocupremia-related myeloneuropathy following gastrojejunal bypass surgery.
AB  - Gastrojejunal bypass surgery may be complicated by nutritional deficiencies,
      including trace elements. Copper, which is absorbed in the duodenum and proximal
      jejunum, is poorly absorbed when a significant portion of the proximal small
      intestine is bypassed. However, despite this theoretical risk of hypocupremia in
      the gastrojejunal bypass patient, reports of symptomatic copper deficiency are
      very rare, and even then the deficiency is often potentiated by an accelerant,
      such as concomitant zinc ingestion. We report a case of hypocupremia resulting in
      hematologic abnormalities and myeloneuropathy after gastrojejunal bypass surgery
      for morbid obesity. It stresses the importance of recognizing nutritional
      deficiencies, particularly copper deficiency, because of the possible and serious
      sequelae of bone marrow suppression and myeloneuropathy. The early recognition
      and treatment of the symptoms of hypocupremia is emphasized to avoid these long
      term sequelae. With the rapidly growing number of patients undergoing
      gastrojejunal bypass surgery for morbid obesity, the index of suspicion for
      hypocupremia must be heightened.

PMID- 21088386
TI  - Nutrition transition and cardiovascular disease risk factors in Middle East and
      North Africa countries: reviewing the evidence.
AB  - AIM: To examine the burden of cardiovascular disease (CVD) risk factors in Middle
      East and North Africa countries and their associations with dietary behaviors as
      nutrition transition is unfolding in the region. DATA: Data on CVD risk factors
      were collected from scholarly papers and a systematic review of published
      articles was performed. Dietary patterns were derived from the WHO Food and
      Agriculture Organization Statistical Databases. RESULTS: Wide variations exist
      across countries in the prevalence of CVD risk factors, namely obesity, diabetes,
      hypertension, hyperlipidemia, smoking and physical inactivity, with some
      countries showing high values of certain factors which approach those observed in
      the developed world. In particular, obesity prevalence rates have reached
      alarming levels, particularly among women in the oil-rich countries (over 40%),
      making it the most pressing health concern in the region. Trends in the dietary
      pattern illustrated a consistent rise in total energy supply by approximately 730
      kcal per capita per day between 1970 and 2005. Dietary patterns showed an
      increased consumption of fat and animal protein and a decreased intake of
      carbohydrates, particularly whole grain cereals, and fresh fruits and vegetables.
      CONCLUSION: Regional differences were attributed to differences in lifestyle,
      occupation and a shift from traditional food habits. Our understanding of the CVD
      disparities across various geographic regions is key to our effort in planning
      relevant intervention programs. Public health efforts should focus on obesity,
      physical inactivity and unhealthy dietary practices. The success of these
      interventions depends on governmental commitment, multisectoral partnership and a
      consideration of the sociocultural norms of the target population.

PMID- 21088387
TI  - Effect of weight loss maintenance on arterial compliance and metabolic and
      inflammatory parameters: a three-year follow-up study.
AB  - BACKGROUND/AIMS: To evaluate the effect of long-term weight loss maintenance on
      arterial compliance, and metabolic and inflammatory parameters in obese patients
      who participated in a 6-month weight loss program featuring nutritional and
      exercise intervention. METHODS: Sixty-seven obese subjects who participated in a
      6-month weight loss program were followed for an additional 30 months. The 47
      patients who fully completed the 3-year follow-up were divided into two groups
      according to change in BMI from the end of the weight loss program to the long
      term follow-up visit. Group 1 included 22 patients whose BMI decreased or
      remained stable; group 2 included 25 patients whose BMI increased after program
      discontinuation. Arterial compliance and metabolic measures were evaluated at
      baseline, and at 3, 6 and 36 months of follow-up. RESULTS: BMI changed from 35.4
      +/- 6.9 to 32.6 +/- 6.6 after 6 months and to 33.4 +/- 7.0 after 36 months. While
      53% of participants regained weight after program discontinuation, the mean
      weight at 3 years remained lower than at entry into the study. Large artery
      elasticity index (LAEI) as well as small artery elasticity index (SAEI) increased
      during initial weight loss program in both groups. After program discontinuation,
      significant improvement in SAEI was observed in patients who decreased or did not
      change BMI, whereas SAEI decreased in subjects who gained weight. LAEI increased
      marginally in group 1, while it significantly decreased in group 2. CONCLUSIONS:
      Obese subjects who successfully completed a 6-month behavioral weight loss
      program and decreased or maintained weight during 30 additional months exhibited
      improved arterial stiffness compared to subjects who regained weight.

PMID- 21088388
TI  - Greater consumption of sweetened beverages and added sugars is associated with
      obesity among US young adults.
AB  - BACKGROUND/AIMS: This study sought to examine the associations of the consumption
      of sugar-sweetened beverages and of added sugars with total and abdominal obesity
      in American adults aged 20-39 years who participated in the 1999-2000 National
      Health and Nutrition Examination Survey in the U.S. METHODS: This was a cross
      sectional study based on a sample of 947 adults (aged 20-39 years): 424 non
      Hispanic whites, 222 non-Hispanic blacks, and 301 Mexican-Americans. Obesity was
      defined as a body mass index >=30 and abdominal obesity as a waist circumference
      >102 cm in men or >88 cm in women. The use of sweetened beverages and added
      sugars was stratified into quartiles of intake. Odds ratios (ORs) for total and
      abdominal obesity were estimated with logistic regression models. RESULTS:
      Compared to the lowest intake quartile of sweetened beverages, those with the
      highest intake had a higher intake of energy, added sugars, and carbohydrates, as
      well as a lower intake of fiber, orange juice, and low-fat milk. A greater intake
      of sweetened beverages was associated with a higher risk of total and abdominal
      obesity (p(trend) <0.02 for both). The adjusted ORs comparing 2 extreme quartiles
      of sweetened beverages were 2.1 (95% CI 1.2-3.7) for total obesity and 2.0 (95%
      CI 1.1-3.6) for abdominal obesity. CONCLUSIONS: An increased consumption of
      sweetened beverages was associated with total and abdominal obesity in US adults
      aged 20-39 years. Further investigation of the potential role of sweetened
      beverages and other dietary components, and of the mechanisms by which these
      intakes contribute to weight gain, is needed to accelerate our efforts to halt or
      somewhat alleviate the current obesity epidemic facing the American population.

PMID- 21088389
TI  - Uric acid in hypertension and renal disease: the chicken or the egg?
AB  - After uric acid was recognized as the causative factor in gout, increased
      prevalence of renal disease and hypertension in this patient population caught
      the attention of the medical community. Thus, it has been proposed that uric acid
      might have caused these disorders. However, uric acid suffered a long period of
      ignorance in which it was considered a metabolically inert substance. However,
      recent years has witnessed a resurrection of interest. Experimental studies
      showed an association between increased uric acid and renal arteriolar disease
      and hypertension. These preliminary results were supported with clinical studies.
      However, controversy regarding the precise pathophysiologic role of uric acid in
      inducing hypertension and renal disease remains to be elucidated. Despite being
      limited at this time, a few randomized intervention studies showed that even
      treatment of asymptomatic hyperuricemia was beneficial in terms of blood pressure
      regulation and kidney function. In this review, we focus on the pathophysiologic
      role of uric acid in the development and progression of renal disease and
      hypertension. We also discuss recent clinical evidence suggesting a causal role
      of uric acid in these disease states.

PMID- 21088390
TI  - Risk of recurrent cerebrovascular events in patients with cryptogenic stroke or
      transient ischemic attack and patent foramen ovale: the FORI (Foramen Ovale
      Registro Italiano) study.
AB  - BACKGROUND: The optimal management of patients with cryptogenic ischemic stroke
      found to have a patent foramen ovale (PFO) at diagnostic workup remains unclear.
      The aims of this observational multicenter study were to evaluate: (1) the risk
      of recurrent cerebrovascular events in patients with cryptogenic minor ischemic
      stroke or transient ischemic attack (TIA) and PFO who either underwent
      percutaneous PFO closure or received only medical treatment, and (2) the risk
      factors associated with recurrent events. METHODS: Consecutive patients (aged 55
      years or less) with first-ever cryptogenic minor ischemic stroke or TIA and PFO
      were recruited in 13 Italian hospitals between January 2006 and September 2007
      and followed up for 2 years. RESULTS: 238 patients were included in the study
      (mean age 42.2 +/- 10.0 years; 118 males); 117 patients (49.2%) received only
      antithrombotic therapy while 121 patients underwent percutaneous PFO closure
      (50.8%). Stroke as the qualifying event was more common in the medical treatment
      group (p = 0.01). The presence of atrial septal aneurysm and evidence of 20
      bubbles or more on transcranial Doppler were more common in the PFO closure group
      (p = 0.002 and 0.02). Eight patients (6.6%) experienced a nonfatal complication
      during PFO closure. At the 2-year follow-up, 17 recurrent events (TIA or stroke;
      3.6% per year) were observed; 7 of these events (2.9% per year) occurred in the
      percutaneous PFO closure group and 10 events (4.2% per year) in the medical
      treatment group. The rate of recurrent stroke was 0.4% per year in patients who
      underwent percutaneous closure (1 event) and 3.4% per year in patients who
      received medical treatment (8 events). On multivariate analysis, percutaneous
      closure was not protective in preventing recurrent TIA or stroke (OR = 0.1, 95%
      CI = 0.02-1.5, p = 0.1), while it was barely protective in preventing recurrent
      stroke (OR = 0.1, 95% CI = 0.0-1.0, p = 0.053). CONCLUSIONS: The results of this
      observational, nonrandomized study suggest that PFO closure might be superior to
      medical therapy for the prevention of recurrent stroke. Periprocedural
      complications were the trade-off for this clinical benefit. Controlled randomized
      clinical trials comparing percutaneous closure with medical management are
      required.

PMID- 21088391
TI  - Exploration of a hypothesized independent association of a common 9p21.3 gene
      variant and ischemic stroke in patients with and without angiographic coronary
      artery disease.
AB  - BACKGROUND: Single-nucleotide polymorphisms (SNPs) at the chromosome 9p21.3 locus
      are associated with coronary artery disease (CAD). An association of this genomic
      region with ischemic stroke independent of its effect on CAD could suggest an
      additional, stroke-specific pathophysiological relationship. METHODS: Medical
      record review was used to identify 548 patients without a history of
      cerebrovascular disease and 232 who had a verified ischemic stroke or transient
      ischemic attack (TIA) from the Duke CATHGEN biorepository of patients who had a
      cardiac catheterization. ANCOVA and multivariable logistic regression modeling
      were performed to determine independent genetic associations between the key
      chromosome 9p21.3 SNP, rs10757278, and ischemic stroke by comparing allele
      frequencies between 229 patients with stroke or TIA and an equal number of
      matched nonstroke controls, adjusting for other risk factors. In a secondary
      analysis, controls were further divided based on the presence (n = 353) or
      absence (n = 195) of angiographic CAD. RESULTS: Allele frequencies were similar
      between patients with and without a history of ischemic stroke in both additive
      (p = 0.83) and dominant (p = 0.92) models of genetic risk. There was no
      association between rs10757278 allele frequency and stroke status based on the
      presence or absence of angiographically demonstrated CAD in nonstroke controls
      (ANCOVA, p = 0.99). CONCLUSION: These results provide no evidence of a stroke
      specific association of the 9p21.3 locus regardless of the presence or absence of
      angiographic CAD and highlight the need for larger studies to further evaluate
      this hypothesized relationship.

PMID- 21088392
TI  - Reduced estimated glomerular filtration rate is associated with stroke outcome
      after intravenous rt-PA: the Stroke Acute Management with Urgent Risk-Factor
      Assessment and Improvement (SAMURAI) rt-PA registry.
AB  - BACKGROUND: The aim of this study was to determine whether renal dysfunction
      affects the outcome of stroke patients treated with recombinant tissue
      plasminogen activator (rt-PA). METHODS: A retrospective, multicenter,
      observational study was conducted to identify the effects of underlying risk
      factors on intravenous rt-PA therapy using 0.6 mg/kg alteplase in 10 stroke
      centers in Japan. Consecutive stroke patients with a premorbid modified Rankin
      Scale (mRS) score <=3 who received rt-PA were studied. Renal dysfunction was
      defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 on
      admission. The outcome measures were any intracerebral hemorrhage (ICH) and
      symptomatic ICH within the initial 36 h; favorable (mRS 0-1) outcome, poor
      outcome (mRS 4-6) and mortality at 3 months. RESULTS: Of a total of 578 patients
      (372 men; 64.4%, 71.4 +/- 11.7 years old), renal dysfunction was present in 186
      patients (32.2%). These patients were older and more commonly had hypertension,
      atrial fibrillation, prior ischemic heart disease and prior use of antithrombotic
      agents than patients without renal dysfunction. ICH (27.4 vs. 16.6%) and
      symptomatic ICH (8.1 vs. 2.6%) was more common in patients with renal dysfunction
      than in those without. At 3 months, patients with renal dysfunction had higher
      median mRS scores than those without (3 vs. 2). After multivariate adjustment for
      established outcome predictors, renal dysfunction was related to any ICH (odds
      ratio 1.81, 95% confidence interval 1.16-2.84), symptomatic ICH (2.64, 1.10
      6.56), poor outcome (1.55, 1.01-2.38), and mortality (2.94, 1.38-6.42).
      CONCLUSIONS: Reduced eGFR was associated with early ICH and 3-month unfavorable
      outcome in stroke patients receiving intravenous rt-PA.

PMID- 21088393
TI  - Compassionate use of linezolid for adult Taiwanese patients with bone and joint
      infections.
AB  - BACKGROUND: Compassionate use of linezolid for bone and joint infections has been
      reported and hematological adverse reactions are a cause for concern. A similar
      experience in Asian people has not been reported. METHODS: Adult cases that
      received linezolid for bone and joint infections at 3 Taiwanese medical centers
      from 2002 to 2006 were analyzed. We investigated factors associated with
      treatment outcome and hematological adverse reactions. RESULTS: Of the 51 cases
      that received linezolid for more than 3 days, 41 (80.4%) had a favorable outcome
      and 10 had a failed outcome. Based on univariate analysis, patients with
      renal/urinary tract diseases, gastrointestinal diseases, higher WBC counts, a
      higher alanine aminotransferase level, or a higher creatinine level prior to
      linezolid treatment were significantly associated with a failed outcome. Based on
      multivariate analysis, underlying gastrointestinal disease was the only
      significant factor for a failed outcome. Six patients stopped linezolid use due
      to adverse reactions. A failed outcome was significantly associated with anemia
      caused by linezolid. CONCLUSION: Linezolid is an effective salvage agent for bone
      and joint infections. However, adverse effects, especially hematological
      reactions, may cause drug discontinuation.

PMID- 21088394
TI  - Effect of S-1 adjuvant chemotherapy on survival following recurrence and efficacy
      of first-line treatment in recurrent gastric cancer.
AB  - BACKGROUND: As S-1 monotherapy has recently become the standard adjuvant regimen
      for stage II-III gastric cancer patients after curative gastrectomy in Japan, the
      question whether adjuvant S-1 affects the subsequent clinical course of relapsed
      patients has attracted great concern. PATIENTS AND METHODS: We retrospectively
      evaluated the effect of adjuvant S-1 on survival following recurrence and
      efficacy of first-line treatment in patients with recurrent gastric cancer after
      curative gastrectomy. A total of 89 patients were evaluated. Thirty patients
      received adjuvant S-1 (cohort A), 10 patients were given adjuvant chemotherapy
      with other oral 5-FU agents (cohort B) and 49 patients received no adjuvant
      chemotherapy (cohort C). RESULTS: Median survival time following recurrence was
      287 days in cohort A, 451 days in B and 547 days in C, with a significant
      difference between A and C (p = 0.0034). Response rates of the first-line
      chemotherapy after recurrence were 6.7, 30.0 and 42.9% in cohorts A, B and C,
      respectively, with a significant difference between A and C (p = 0.0007). On
      multivariate analysis, S-1 adjuvant chemotherapy was independently associated
      with poor prognosis after recurrence (hazard ratio 2.64). CONCLUSION: S-1
      adjuvant chemotherapy significantly reduced survival and response to first-line
      chemotherapy following recurrence in patients with recurrent gastric cancer.

PMID- 21088395
TI  - In vitro activity of dalbavancin against staphylococci isolated in Istanbul,
      Turkey.
AB  - BACKGROUND: Staphylococci are a major cause of both community- and hospital
      acquired infections. Dalbavancin is a new bactericidal second-generation
      lipoglycopeptide antibiotic to use in the treatment of multidrug-resistant
      staphylococcal infections. It is important to determine its activity against
      staphylococci isolated in Turkey. Dalbavancin has not yet been used in
      antimicrobial therapy in our country. METHOD: Dalbavancin was tested against a
      total of 453 staphylococcal strains by using the reference broth microdilution
      method. Organisms tested included: methicillin-resistant Staphylococcus aureus
      (MRSA; 237 strains), methicillin-susceptible S. aureus (MSSA; 144 strains) and
      methicillin- resistant coagulase-negative staphylococci (MR-CoNS; 72 strains).
      RESULTS: MIC(50) and MIC(90) values of dalbavancin against MRSA, MSSA and MR-CoNS
      were found as <=0.008 and 0.25 mg/l; 0.016 and 0.125 mg/l; and 0.016 and 0.5
      mg/l, respectively. The overall distribution of dalbavancin MIC values ranged
      from <=0.008 to 2 mg/l. If the interpretive breakpoint MIC value is <=1 mg/l, the
      susceptibility rates of MRSA, MSSA and MR-CoNS strains were determined as 99.6,
      100 and 98.6%, respectively. CONCLUSION: The MIC results for dalbavancin have
      demonstrated a good activity against both methicillin-sensitive and -resistant
      staphylococci isolated from hospitalized patients.

PMID- 21088396
TI  - Resistance status and evolution trends of Klebsiella pneumoniae isolates in a
      university hospital in Greece: ineffectiveness of carbapenems and increasing
      resistance to colistin.
AB  - BACKGROUND: Due to its increased non-susceptibility rates, Klebsiella pneumoniae
      has emerged as one of the most problematic pathogens. METHODS: The level of
      resistance to 25 antimicrobials of K. pneumoniae isolates from a teaching
      hospital in Greece and the evolution trends during 2 decades were examined.
      RESULTS: A statistically significant increase in non-susceptibility rates was
      found for almost all antimicrobials examined. During 2008, the isolates presented
      non-susceptibility rates to aminoglycosides >50% and to quinolones >60%.
      Nowadays, 1 out of 10 isolates is non-susceptible to colistin. Moreover, the
      isolates non-susceptible to imipenem were almost doubled between 2007 (29%) and
      2008 (50%). Among the imipenem-resistant isolates, 1 out of 4 was also resistant
      to colistin. CONCLUSION: The effectiveness of carbapenems has been compromised
      and the increase in resistance to colistin is rapid and steep.

PMID- 21088397
TI  - Phase I study of S-1 plus nedaplatin in patients with advanced/recurrent head and
      neck cancer.
AB  - BACKGROUND: Cisplatin plus fluorouracil is widely used for the treatment of head
      and neck cancer. However, the cisplatin plus fluorouracil regimen necessitates
      hospitalization. Therefore, we planned to develop a new regimen that can be
      administered on an outpatient basis and performed a phase I study of S-1 +
      nedaplatin. METHODS: S-1 was given orally at a fixed dose for 14 days, and
      nedaplatin was administered intravenously on day 8 of S-1 administration. The
      dose of nedaplatin was increased in 10-mg/m(2) steps to find the maximum
      tolerated dose, depending on the appearance of dose-limiting toxicities. RESULTS:
      A total of 14 patients were registered. The maximum tolerated dose of nedaplatin
      was determined to be 90 mg/m(2). The main toxicities were neutropenia and
      thrombocytopenia. The response rate was 57.1%. CONCLUSION: The recommended dose
      of nedaplatin for a phase II study was determined to be 80 mg/m(2). We concluded
      that our regimen was well tolerated and that the response rate was acceptable.

PMID- 21088398
TI  - Meta-analysis of incidence and risk of hypomagnesemia with cetuximab for advanced
      cancer.
AB  - BACKGROUND: Cetuximab is often used in patients with colorectal cancer, head and
      neck cancer, and other cancers. Hypomagnesemia is a major adverse event that was
      often ignored in studies. The aim of this meta-analysis is to gain a better
      understanding of the overall incidence and risk of hypomagnesemia in patients who
      received cetuximab-based therapy. METHODS: Databases, including Pubmed, EMBASE,
      The Cochrane Library, American Society of Clinical Oncology (2000-2008), and Web
      of Science, were searched to identify relevant studies. Eligible studies were
      prospective phase II/III clinical trials of patients with cancer assigned
      cetuximab at a dose of 400 mg/m(2) i.v. on day 1 and 250 mg/m(2) weekly
      thereafter. The primary endpoint was incidence of hypomagnesemia. RESULTS:
      Nineteen clinical reports were identified which included a total of 4,559
      patients available for analysis, with 3,081 patients assigned cetuximab-based
      treatment. This result showed a high incidence of grade 3 and 4 hypomagnesemia
      (5.6%; 95% CI = 3.0-10.2) and a high incidence of all-grade hypomagnesemia
      associated with cetuximab-based therapy for advanced cancer (36.7%; 95% CI = 22
      54.4). Compared with non-cetuximab therapy, cetuximab-based therapy has a higher
      risk of grade 3 and 4 hypomagnesemia (4.75; 95% CI = 3.661-6.18) and all-grade
      hypomagnesemia (4.75; 95% CI = 3.661-6.18). CONCLUSION: Cetuximab-based therapy
      is associated with a significant risk of hypomagnesemia. Early monitoring and
      effective management of hypomagnesemia are important for patients that received
      cetuximab-based therapy.

PMID- 21088399
TI  - Postantibiotic effects of tigecycline, colistin sulfate, and levofloxacin alone
      or tigecycline-colistin sulfate and tigecycline-levofloxacin combinations against
      Acinetobacter baumannii.
AB  - BACKGROUND: Colistin sulfate and levofloxacin, alone and in combination with
      tigecycline, were investigated for their in vitro activities and postantibiotic
      effects (PAEs) on6 meropenem-resistant Acinetobacter baumannii. METHODS: The in
      vitro activities of colistin sulfate and levofloxacin in combination with
      tigecycline were determined using a microbroth checkerboard technique. The
      results were interpreted based on the fractional inhibitory concentration index.
      To determine the PAEs, A. baumannii strains in the logarithmic phase of growth
      were exposed for 1 h to antibiotics, alone and in combination. Recovery periods
      of test cultures were evaluated using viable counting after centrifugation.
      RESULTS: One synergistic interaction was observed for each of the tigecycline
      colistin sulfate and tigecycline-levofloxacin combinations. Colistin sulfate
      produced a strong PAE ranging from 2.50 to 7.0 h in a concentration-dependent
      manner. PAEs were induced by levofloxacin (ranging from 0.35 to 2.45 h) and
      tigecycline (ranging from 0.05 to 1.40 h). In combination, tigecycline slightly
      changed the PAE of colistin sulfate and levofloxacin against the studied strains.
      CONCLUSION: This study's findings could have important implications for the
      timing of doses during antimicrobial therapy with tigecycline, colistin sulfate,
      and levofloxacin alone and in combination.

PMID- 21088400
TI  - Low lymphocyte ratio as a novel prognostic factor in acute heart failure: results
      from the Pre-RELAX-AHF study.
AB  - BACKGROUND: Previous studies have suggested that a lower lymphocyte ratio (Ly%)
      in the white blood cell (WBC) differential count is related to worse outcomes in
      patients with acute heart failure (AHF) and other cardiovascular disorders.
      METHODS: In the Pre-RELAX-AHF study, 234 patients with AHF, systolic blood
      pressure >125 mm Hg and brain natriuretic peptide >=350 pg/ml or equivalent were
      randomized to 1 of 4 intravenous doses of relaxin or placebo and followed up for
      6 months following randomization. Complete blood count and differential were
      performed by a central laboratory at baseline and then daily to day 5 and on day
      14. RESULTS: The WBC count by itself was not associated with measures of disease
      severity or outcome, and patients with Ly% <13% had similar baseline
      characteristics to patients with Ly% >13%, except for a higher baseline WBC
      count, elevated baseline glucose, older age and higher rates of peripheral
      vascular disease. However, patients with Ly% <13% had less improvement of
      dyspnea, greater worsening of heart failure, longer length of initial hospital
      stay and fewer days alive and out of hospital. Statistical significance was
      reached for all-cause death by days 60 and 180 (hazard ratio = 1.11 per percent
      decrease, 95% confidence interval 1.03-1.19; p = 0.0048). CONCLUSIONS: Despite no
      association with any baseline characteristic known to strongly predict outcome in
      AHF, low Ly% is associated with less symptom relief and worse in-hospital and
      postdischarge clinical outcomes.

PMID- 21088402
TI  - Saliva substitutes in combination with highly concentrated fluorides and
      brushing: in vitro effects on enamel subsurface lesions.
AB  - Hyposalivation is often associated with high caries activity, in particular in
      patients undergoing irradiation in the head/neck area. Besides the use of saliva
      substitutes to relieve the oral symptoms, daily application of fluoride gels or
      toothpaste (5,000 MUg F-/g) is recommended for caries prevention. The aim of this
      study was to evaluate potentially remineralising effects of these fluoride agents
      in combination with saliva substitutes on enamel subsurface lesions.
      Demineralised bovine specimens were either stored in mineral water [control;
      saturation with respect to octacalcium phosphate (S(OCP)): 0.8], a demineralising
      saliva substitute (Glandosane; S(OCP): 0.3) or in a modified (with respect to
      S(OCP)) saliva substitute [Saliva natura (SN); S(OCP): 1.9] for 5 weeks (37
      degrees C). The following treatments were applied twice daily (11-13/group): no
      treatment (0), ProSchmelz fluoride gel (PS; 10 min application), Duraphat
      toothpaste (DP; 10 s; brushing with toothpaste/storage solution slurry),
      combination of DP+PS. Mineral parameters before/after storage were evaluated from
      microradiographs. Storage in Glandosane led to significant demineralisation (p <
      0.05; paired t test), whereas additional use of fluoride agents neutralised the
      demineralising effect (p > 0.05). Storage in water alone resulted in no changes
      in mineral parameters (p > 0.05), whereas in combination with fluorides
      remineralisation could be shown (p < 0.05). For SN alone, remineralisation was
      observed (p < 0.05), but no additional beneficial effects of fluorides were
      detected. Under the conditions chosen, the fluoride agents reduce the
      demineralising effects of Glandosane and promote the remineralisation of
      specimens stored in water. Remineralising effects of SN could not be enhanced by
      the fluorides.

PMID- 21088401
TI  - Sealing distal proximal caries lesions in first primary molars: efficacy after
      2.5 years.
AB  - BACKGROUND: The prevalence of proximal caries in primary molar teeth is high in
      many countries. AIMS: (1) To study by means of a split-mouth design the 1- and
      2.5-year efficacy of sealing proximal lesions vs. flossing instructions (control)
      on primary molar teeth. (2) To assess children's behaviour and pain perception
      during the procedure. METHODS: Ninety-one 4- to 6-year-old children from Bogota,
      Colombia participated. Participants had to have at least two proximal lesions
      scored according to the following radiographic classification system:
      radiolucency (1) in enamel outer half, (2) restricted to enamel-dentine junction,
      or (3) restricted to dentine outer third. Baseline, 1- and 2.5-year follow-up
      bitewing radiographs were taken. Test and control lesions were randomly selected.
      After temporary separation test lesions were sealed (adhesive).
      Parents/caregivers received a flossing leaflet for their children. Progression of
      the lesions was assessed by means of independent reading of conventional bitewing
      radiographs. RESULTS: One-year (n = 73) test vs. control lesion progression was
      27.4 vs. 50.7%, respectively (p < 0.01, McNemar's test), and 2.5-year (n = 56)
      test vs. control lesion progression was 46.4 vs. 71.4%, respectively (p < 0.01).
      The dropouts did not differ from those who remained in the study regarding
      relevant caries baseline data. More than 88% of the participants presented
      positive to definitively positive behaviour and very low or low pain intensity at
      both first and second appointments. CONCLUSION: The sealing technique was
      superior to flossing instructions both after 1 and 2.5 years of follow-up and the
      majority of the participants had no anxiety or pain during the treatment.

PMID- 21088403
TI  - Chronic inflammation is an important risk factor for the development of
      gastrointestinal cancer. Preface.

PMID- 21088404
TI  - Inflammation and immunity in the tumor environment.
AB  - The relationship between inflammation, innate immunity and cancer is widely
      accepted. Cancer-associated inflammation includes infiltrating leukocytes,
      cytokines, chemokines, growth factors, lipid messengers and matrix-degrading
      enzymes. Tumor-associated macrophages and lymphocyte subpopulations are major
      components of the leukocyte infiltrate in most tumors. However, the cytokine and
      chemokine expression profile of the tumor microenvironment may be more relevant
      than its specific immune cell content. Apart from inflammatory cells, tumor
      stroma consists of new blood vessels and connective tissue. Many factors produced
      by tumor cells promote tumor angiogenesis and generation of extracellular matrix.
      Investigations regarding the link between inflammation and cancer are vital for
      identifying cell or protein targets for cancer prevention and therapy. Based on
      the relation between inflammation and cancer, different forms of immunotherapy
      have been developed. In a mouse model, we investigated the potential of
      Streptococcus pyogenes to achieve a bacteria-related immune response against
      tumor cells followed by tumor regression. As a model of pancreatic carcinoma, the
      aggressively growing and poorly immunogenic Panc02 tumor model was chosen. Our
      findings showed that a local application of bacteria mediates complete tumor
      regression. Future investigations should focus on the optimization of
      immunotherapeutic approaches that incorporate live bacteria or bacterial
      components.

PMID- 21088405
TI  - Oxidative stress and inducible nitric oxide synthase induction in carcinogenesis.
AB  - BACKGROUND: Chronic inflammation is linked to an increased risk of cancer. The
      molecular mechanisms underlying this correlation have been long investigated and
      it is well known that the inflammatory cells recruited in the inflamed tissues
      release chemical mediators, in particular reactive oxygen species (ROS). With
      respect to digestive systems, ROS have been implicated in a number of
      pathologies, including Helicobacter pylori-related gastritis, Barrett's
      esophagus, inflammatory disease of the lower gastrointestinal tract, alcoholic
      liver disease and several other types of toxic and virus-mediated liver injury.
      ROS levels within cells and tissues are controlled by numerous antioxidant
      defense mechanisms, but in inflammation, ROS overproduction exceeds defenses and
      damage intracellular macromolecules, including nucleic acids, with formation of
      potentially mutagenic and carcinogenic DNA adducts. AIMS: This paper summarizes
      our own experience investigating the link between inflammation, ROS production
      and oxidative DNA damage as well as the impact of the above events on cytokine
      and growth factor release, oncogene activation, telomere instability and microRNA
      in H. pylori-related gastritis, Barrett's esophagus and, in particular, hepatitis
      C virus-related liver disease. The paper also describes, at least in part, the
      complex scenario involving nitric oxide production and its impact in some
      gastrointestinal diseases, as well as a number of other molecular and biochemical
      changes related to ROS production and inflammation. CONCLUSIONS: The paper falls
      obviously short of being an exhaustive summary of our understanding, but the data
      reported are intended as a stimulus to broaden the knowledge on the topic, also
      in view of the possible therapeutic implications of any advance obtained.

PMID- 21088406
TI  - Role of cyclooxygenase-2 in pathogenesis and prevention of colorectal cancer.
AB  - Chemoprevention of colorectal cancer is a promising science that has particular
      importance due to the limited success of current treatments for most advanced
      common malignancies. Many chemopreventive agents have been studied including
      cyclooxygenase (COX) inhibitors. Two isoforms of the COX enzymes are COX-1 and
      COX-2. COX-1 is constitutively expressed in normal tissue, serving an important
      role in tissue homeostasis, whereas COX-2 is an inducible enzyme, which is
      markedly overexpressed at sites of inflammation and colorectal neoplasms. The
      preventive efficacy of traditional nonsteroidal anti-inflammatory drugs (NSAIDs),
      which inhibit COX-1 and/or COX-2, has considerable support from animal and
      epidemiological studies; however, there are well-documented toxicities associated
      with NSAID use. These adverse effects are attributed to NSAIDs' inhibition of COX
      1. The development of COX-2 specific inhibitors gave hopes of bypassing the
      associated traditional NSAID toxicities while better targeting tissues sustaining
      inflammation and neoplasia. The PrsSAP, APC and APPROVe trials demonstrated the
      efficacy of COX-2 specific inhibitors in preventing the recurrence of sporadic
      colorectal polyps. However, the trials were terminated early due to discovery of
      significant cardiovascular toxicity, although the exact extent of this toxicity
      remains unclear. The exact mechanisms through which NSAIDs exert their cancer
      preventing effects are currently unknown; inhibition of COX-2 is of great
      importance, but COX-2 independent pathways exist as well. In addition, the
      efficacy of NSAID use for cancer prevention can differ significantly between
      individuals. Personalized medicine in this field is also greatly anticipated.
      Combination therapy is under extensive research in order to improve efficacy
      while reducing toxicity profiles. Chemoprevention of colorectal cancer is largely
      possible, but the ultimate drug and proper patient selection, among other
      elements of the cancer prevention equation, are still needed.

PMID- 21088407
TI  - Chronic inflammation, colorectal cancer and gene polymorphisms.
AB  - Chronic inflammation is commonly present in gastrointestinal mucosal sites at
      increased risk for cancer, such as in inflammatory bowel disease (IBD) or chronic
      gastritis caused by Helicobacter pylori infection. Why some patients have more
      mucosal inflammation than others, and why certain individuals with chronic
      inflammation develop cancer, are problems that have not been solved. Unlike the
      case for the syndromic forms of familial colorectal cancer (CRC), the risks for
      IBD and other forms of chronic inflammation have not been linked to highly
      penetrant single gene mutations. Single nucleotide polymorphisms (SNP) are
      variations in DNA sequence that can be linked to any phenotype (cancer, chronic
      inflammation, etc.) in genome-wide association studies (GWAS). CRC has been
      linked to several highly penetrant single gene loci, as well as multiple SNP. The
      propensity to develop IBD has not been linked to single gene mutations in most
      instances, but has been linked to SNP in the NOD2 locus (which appear to create
      hypomorphic alleles for this bacterial response gene), the IL23R locus, the
      autophagy gene ATG16L1 and a wide range of other loci including the Toll-like
      receptors, JAK2 and STAT3, and perhaps 70 more. At present, the problem in
      predicting risk for chronic inflammation is that there are many genetic
      polymorphisms with relatively modest individual effects. Our challenge is to
      understand how the SNPs that are linked to variations in the inflammatory
      response interact with one another (i.e. to understand the 'epistasis' involved),
      and to integrate this with the variety of individual environmental exposures.
      This represents an opportunity for informatics science to help personalize our
      approach to chronic inflammatory diseases of the gut and identify those at
      greatest risk for cancer.

PMID- 21088408
TI  - Chronic liver diseases as liver tumor precursors.
AB  - Liver cancer is a major global health problem and hepatocellular carcinoma (HCC)
      accounts for 75% of all liver carcinoma. HCC occurs more often in men than in
      women and mostly in people 50 to 60 years old. The disease is more common in
      parts of sub-Saharan Africa and Asia than in North and South America and Europe.
      Nevertheless its incidence increased over the past 4 decades in some Western
      countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most
      common cause of cancer mortality (behind only lung and colorectal cancer) with
      approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC
      almost entirely develops in the context of inflammation and organ injury and is
      related to cirrhosis in about 85% of the cases. Among underlying etiologies of
      liver cirrhosis, most frequent are viral infection and toxic substances, mostly
      alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus
      infection. Hepatitis C virus infection is the main risk factor in Western
      countries. Hereditary hemochromatosis is not a very frequent cause of liver
      cirrhosis, but these patients are at higher risk for HCC compared with other
      etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of
      plant mold, can play a role in some countries in Asia and Africa, and can have a
      synergistic effect with hepatitis B infection.

PMID- 21088409
TI  - Gastric cancer: epidemiology and risk factors.
AB  - The incidence of gastric cancer is decreasing and lies between 10 and 15 new
      cases per 100,000 population per year in most Western countries. Peak age is
      between 60 and 80 years. While distal gastric cancers account for the overall
      decrease in gastric cancer, tumors in the proximal stomach (cardia and
      esophagogastric junction) are on the rise. Recognized risk factors for gastric
      cancer are infection with Helicobacter pylori, dietary factors (e.g. high intake
      of salt-preserved foods), smoking, pernicious anemia and a history of partial
      gastrectomy.

PMID- 21088410
TI  - Molecular pathogenesis of Helicobacter pylori infection: the role of bacterial
      virulence factors.
AB  - Helicobacter pylori is one of the most common pathogens affecting humankind,
      infecting approximately 50% of the world's population. Of those infected, many
      will develop asymptomatic gastritis, but 10% develop gastric or duodenal ulcers.
      The clinical outcome of the infection may involve a combination of bacterial
      factors, host factors and environmental factors. In the process of development of
      gastritis, ulceration and cancer, several cellular and molecular steps follow
      each other. Infection, acid survival, adhesion, cytotoxicity, epithelial cell
      turnover changes, inflammation, regeneration or pathological alteration towards
      erosions, ulceration, and cancer can be observed on the cellular level. Bacterial
      factors like urease, AmiE, AmiF, hydrogenase and arginase are needed for survival
      in the acidic gastric environment. The bacterial flagellae are essential to move
      the bacteria towards the epithelial surface. Adhesive factors like BabA, SabA and
      ureaseA are necessary for adhesion against MHC-II complexes and Le antigens. The
      bacteria VacA and CagA are cytotoxic factors. The Cag type IV secretion system
      delivers these proteins inside the epithelial cells. After disruption of
      epithelial cell junctions, the bacteria can pass through the gastric wall facing
      direct immune response from neutrophils, lymphocytes, mast cells and dendritic
      cells. This review describes and summarizes our present molecular biological
      information and knowledge about the Helicobacter infective component, cell
      functions and processes. The possible role of host counter responses and
      interactions with gastric epithelia and immune cells are also detailed.

PMID- 21088411
TI  - From gastric inflammation to gastric cancer.
AB  - The majority of gastric adenocarcinomas are related to chronic inflammation
      induced by Helicobacter pylori infection. For intestinal-type gastric cancer, a
      multistep process of mucosal alterations leading from gastritis via glandular
      atrophy, intestinal metaplasia and dysplasia to invasive carcinoma is well
      recognized. Ongoing clinical studies focus on a 'point of no return'. It is
      defined as a situation when certain alterations are no longer reversible by H.
      pylori eradication and progression to gastric cancer may continue. H. pylori
      affects the mucosal as well as the systemic immune response by secretion of
      cytokines and the recruitment of distinct inflammatory cells. The immune response
      is characterized by a balance between a Th1-dominated response and the
      recruitment of antigen-specific regulatory T cells that allow the bacteria to
      persist in human gastric mucosa. Besides immune-mediated effects, H. pylori
      induces cellular alterations as well as genetic alterations in genes that are
      essential for the epigenetic integrity and mucosal homeostasis. These genetic
      alterations during gastric cancer development are in focus of intensive research
      and should ultimately allow the identification of risk factors involved in
      gastric carcinogenesis. The detection of individuals at high risk for gastric
      cancer would help to design appropriate strategies for prevention and
      surveillance.

PMID- 21088412
TI  - Multimodal therapy of gastric cancer.
AB  - Adenocarcinoma of the stomach is the 2nd most common cancer worldwide. The 5-year
      survival rates after curative surgical resection decline from 60-90% in stage I,
      to 30-50% in stage II and finally drop to only to 10-25% for patients in stage
      III of this disease. Surgical treatment is the only therapeutic modality that has
      a potentially curative effect. According to certain criteria, early gastric
      cancer limited to the mucosa or submucosa is indicated for endoscopic mucosal
      resection. In advanced gastric cancer with surgical approach, the questions of
      type of resection, extent of lymph node dissection and indication for splenectomy
      do arise. R0 resection represented with macroscopic- and microscopic-free
      resection margins is the ultimate goal for a surgeon. Chemotherapy is the
      treatment of choice in stage IV for unresectable disease. According to numerous
      randomized controlled trials, adjuvant chemotherapy versus chemoradiotherapy have
      been accepted for stages Ib-IIIb of this disease. Combination chemotherapy seems
      to be more effective than monotherapy. Neoadjuvant chemotherapy is administered
      with the aim to downstage a locally advanced tumor prior to attempting curative
      resection. New therapeutic possibilities include agents like angiogenesis
      inhibitors, human epidermal growth factor receptor family inhibitors and
      inhibitors of small molecules (tyrosine kinase inhibitors). Survival rates in
      resectable gastric cancer are influenced mainly by the depth of invasion through
      the gastric wall and by the presence or absence of regional lymph node
      involvement. Positive margins in resected patients are associated with very poor
      prognosis.

PMID- 21088413
TI  - Inflammatory bowel disease as a risk factor for colorectal cancer.
AB  - Patients with long-term inflammatory bowel disease (IBD), ulcerative colitis (UC)
      and Crohn's colonic disease (CD) have an increased risk of colorectal carcinoma
      (CRC). Eaden's meta-analysis has shown that the risk for CRC in UC patients is 2%
      at 10 years, 8% at 20 years and 18% at 30 years of disease duration. It is now
      accepted that the risk of colorectal cancer is equivalent in both (UC and CD)
      conditions. Duration of disease is recognized to be the most important risk
      factor for CRC development. Extent of disease in another major risk factor. Most
      cancers arise in patients with extensive disease, which is generally defined as
      extension of inflammation beyond the hepatic flexure. It was demonstrated that
      proctitis and proctosigmoiditis posed no increased risk for patients with UC.
      Recent data from case control studies suggests that greater degrees of
      colonoscopic or histologically active inflammation are associated with an
      increased risk of CRC. Recently, it has been proven that shortened tubular colon,
      colonic stricture and postinflammatory polyps should be considered strong risk
      factors for CRC development. Primary sclerosing cholangitis (PSC) in patients
      with UC is associated with substantial risk of CRC. Screening colonoscopy should
      be performed in patients with UC after 8-10 years of disease. The interval
      between surveillance examinations is dependent on each individual's personal risk
      factors. In patients with a previous history of PSC, ongoing active inflammation,
      previous history of dysplasia or strictures, and strong family history of bowel
      cancer, annual surveillance is recommended. Colectomy is strictly recommended for
      patients who were diagnosed with flat high-grade dysplasia (HGD) or CRC and where
      the diagnosis was confirmed by expert gastrointestinal pathologists. In patients
      with a biopsy specimen considered indefinite for dysplasia, guidelines suggest
      colonoscopy between 3 and 12 months. Multifocal low-grade dysplasia (LGD) is a
      stronger indication for colectomy. The optimal colonoscopic surveillance interval
      for patients who were diagnosed with a flat LGD is still unknown, but 3-6 months
      is often recommended. Chemopreventive agents should be used to minimize the risk
      of developing dysplasia or CRC in IBD patients. It has been shown that mesalazine
      has a preventive effect for CRC and dysplasia.

PMID- 21088414
TI  - The use of molecular markers in the diagnosis of colorectal cancer screening.
AB  - BACKGROUND: Colorectal cancer (CRC) is among the most prevalent cancers. Despite
      remarkable advances in detection and treatment of the illness, more than a third
      of patients diagnosed with CRC ultimately succumb to the neoplastic lesions,
      mostly due to metastases. Chromosomal instability, DNA mismatch repair defects,
      epigenetic silencing due to aberrant methylation of promoters, defects in base
      excision repair and activation of oncogenic pathways are the prerequisites for
      CRC development. Early detection of CRC is of paramount importance and the key to
      ultimately curing the vast majority of patients. METHODS: Additionally to testing
      for fecal occult blood, assays for the detection of CRC-specific mutations and
      aberrant promoter methylation of fecal DNA and of DNA isolated from blood have
      been established. Moreover, assays for profiling DNA, RNA and proteins in plasma
      to detect CRC in early stages have been the focus of intense research. RESULTS:
      The improved and newly developed assays described in this article show the
      potential for strongly improved sensitivity at high specificity. Comparison of
      various assays shows that the accuracy of the tests strongly depends on the
      experimental setup and the samples used (e.g. blood vs. stool DNA, early vs. late
      cancer stage). CONCLUSION: The broad implementation of screens for CRC with high
      sensitivity and specificity, as developed in recent years, should strongly
      increase the early detection of neoplastic transformations and thereby, the
      survival rate of cancer patients.

PMID- 21088415
TI  - Advanced endoscopic imaging methods for colon neoplasia.
AB  - The main goal of lumenal endoscopic visualization of the colon is to detect
      mucosal pathologies, which when removed will result in cure or palliation of a
      disease process. Whereas traditionally endoscopic imaging was performed with
      fiber-optic technology, currently there are many new methods that improve our
      visual acuity when evaluating the colon mucosa. Most of these methods are
      collectively called 'advanced colonic imaging'. The 2 main aims of standard
      (white light) and advanced colonic imaging are to enhance the superficial mucosal
      detail (i.e. 'pit pattern') and allow a detailed view of the submucosal capillary
      pattern, thus potentially improving the detection characterization of
      pathological lesions. However, the current literature dealing with most methods
      used for advanced endoscopic imaging of the colon is fraught with many
      controversial findings which have resulted in opposing views regarding its
      utility. Whereas some investigators vehemently support the use of most of these
      methods in routine clinical practice, most experts and practicing endoscopists
      still refuse to accept that these methods aid in the clinical routine. For now,
      white light video-colonoscopy and high-definition white light video-colonoscopy
      will remain the standard endoscopic methods for investigating the colon mucosa
      until new methods convincingly and clearly prove their superiority over white
      light endoscopy.

PMID- 21088416
TI  - Etiology and risk factors for esophageal carcinoma.
AB  - Trends toward increasing incidence rates were observed for esophageal and gastric
      cardia adenocarcinoma in Western countries and were associated with trends toward
      stabilizing or declining incidence rates for esophageal squamous cell carcinoma,
      suggesting that these tumors might be associated with distinct risk factors.
      Overweight and obesity have been consistently related to esophageal
      adenocarcinoma, but not to squamous cell carcinoma. Body mass index seems to be
      inversely related to the risk of esophageal squamous cell carcinoma. The
      influence of obesity on esophageal adenocarcinoma and gastric cardia
      adenocarcinoma may be related to higher incidence of gastroesophageal reflux in
      obese persons since the risk of gastroesophageal reflux is strongly related to
      the risk for Barrett's esophagus. Tobacco smoking is a strong risk factor for
      esophageal squamous cell carcinoma, but is only a weak risk factor for esophageal
      adenocarcinoma. Alcohol consumption is a strong risk factor for esophageal
      squamous cell carcinoma, but is not consistently related to esophageal
      adenocarcinoma. Selenium, dietary fiber, fruits, vegetables and antioxidants are
      seen as protective factors. Male gender seems to be a risk factor for both types
      of tumors in the region, while infection with human papillomavirus does not seem
      to play a major part in the development of esophageal cancers. Infection with
      Helicobacter pylori is, however, an interesting factor to this region of tumors
      as discussed in many reports. It has been suggested that infection with H. pylori
      is protective to adenocarcinoma, but might be a risk factor for squamous cell
      carcinoma, although the role of H. pylori in the etiology of these cancers
      remains somewhat unclear.

PMID- 21088417
TI  - Epidemiology of pancreatic cancer: an update.
AB  - Pancreatic cancer, although infrequent, has a very poor prognosis, making it one
      of the 4 or 5 most common causes of cancer mortality in developed countries. Its
      incidence varies greatly across regions, which suggests that lifestyle factors
      such as diet, and environmental factors, such as vitamin D exposure, play a role.
      Because pancreatic cancer is strongly age-dependent, increasing population
      longevity and ageing will lead to an increase of the global burden of pancreatic
      cancer in the coming decades. Smoking is the most common known risk factor,
      causing 20-25% of all pancreatic tumors. Although a common cause of pancreatitis,
      heavy alcohol intake is associated only with a modest increased risk of
      pancreatic cancer. While viruses do not represent a major risk factor, people
      infected with Helicobacter pylori appeared to be at high risk of pancreatic
      cancer. Many factors associated with the metabolic syndrome, including overweight
      and obesity, impaired glucose tolerance, and long-standing diabetes also increase
      the risk disease, while atopic allergy and use of metformin as a treatment for
      diabetes have been associated with a reduced risk of pancreatic cancer. A family
      history of pancreatic cancer is associated with an increased risk of pancreatic
      cancer and it is estimated that 5-10% of patients with pancreatic cancer have an
      underlying germline disorder. Having a non-O blood group, another inherited
      characteristic, has also been steadily associated with an increased risk of
      pancreatic cancer. While many risk factors for pancreatic cancer are not
      modifiable, adopting a healthy lifestyle could substantially reduce pancreatic
      cancer risk.

PMID- 21088418
TI  - Trends of primary and subsequent cancers of the gastrointestinal tract in the
      Czech population, 1976-2005.
AB  - A total of 355,624 new gastrointestinal (GI) cancers were registered in 1976-2005
      in the Czech Cancer Registry. Of these, there were 14,744 (4.1%) primary and
      26,790 (7.5%) subsequent cases, of which all were GI multiple cancers (12.1%
      males and 11.1% females). The primary GI cancers were followed by 16,362 other
      neoplasms (60.7% males, 39.3% females); the subsequent GI cancers were preceded
      by 31,519 other neoplasms (55.8% males, 44.2% females). Double neoplasms were
      higher in females, and multiple cases were higher in males. The number of primary
      cases peaked in 1997, the number of subsequent cases increased until 2005. Almost
      half of the cases were registered in the age group of 50-69 years. The average
      interval between primary GI cancers and subsequent neoplasms was 6.1 years; the
      ratio of synchronous to metachronous cases was 1:3.6 in males and 1:5 in females.
      The most frequent synchronous cases in males were cancers of other GI, urinary,
      genital and respiratory tract; in females these were cancers of other GI, genital
      and urinary tract and the breast. The most frequent cancers preceding the next
      subsequent GI cancer included primary cancers of the skin, other GI, genital,
      urinary and respiratory tract for males, and those of the skin, genital and other
      GI tract and breast cancer for females. The 23,462 subsequent GI cancers reported
      as a 2nd cancer included early stages in 29.6% of males and 27.9% of females,
      advanced stages in 31.2% males and 31.3% females, and unknown stages in 39.3%
      males and 40.8% females. Of 3,562 primary neoplasms of advanced stages before
      subsequent GI cancers, 2,093 were cases at stage III (51.4% males, 48.6% females)
      and 1,469 cases were at stage IV (60.2% males, 39.8% females); the most frequent
      in males were primary cancers of other GI, respiratory and genital tract, and
      cancers of other GI, breast and genital cancers in females. Of 9,568 primary
      neoplasms before subsequent GI cancers at advantage stages, 3,325 cases were
      registered before stage III (53.9% males, 46.1% females) and 6,243 cases before
      stage IV (57.7% males, 42.3% females). The most frequent in males were primary
      cancers of skin, other GI, genital and urinary tract; for women, the most
      frequent were those of the skin, genital cancers, breast and other GI tract. Up
      to October 2007, 78.2% males died and 21.8% survived primary GI cancers; for
      women, 76.6% of died and 23.4% survived. Of the subsequent GI cancers, 86.7%
      males died and 13.3% survived; for women, 85.7% died and 14.3% survived.

PMID- 21088419
TI  - Is early diagnosis of pancreatic cancer fiction? Surveillance of individuals at
      high risk for pancreatic cancer.
AB  - Pancreatic cancer represents one of the most deadly human malignancies with an
      overall 5-year survival of less than 5%. Despite improvements in imaging
      techniques and surgical techniques, survival statistics have hardly improved over
      the past decades. To improve the dismal outlook it would be highly desirable to
      develop a program to detect precursor lesions or small asymptomatic early cancers
      at the time when the disease is still at a curable stage. Screening the general
      population for disease presence is not feasible at present because of the
      relatively low disease incidence and the lack of a noninvasive, reliable and
      cheap screening tool. Targeted surveillance programs, however, in individuals at
      high risk for developing pancreatic cancer, like mutation carriers of pancreatic
      cancer prone hereditary (tumor) syndromes or individuals with a strong family
      history of pancreatic cancer without a known underlying genetic defect, might be
      feasible. Careful consideration of the criteria put forward by Wilson and Jungner
      as published by the World Health Organization on the principles and practice of
      screening for disease, indicate that surveillance in this high-risk population by
      means of endosonography (EUS) and/or magnetic resonance imaging (MRI) represents
      a promising development, though experimental. It nicely points out which open
      questions need to be addressed. Among others, these include how to acquire a
      better understanding of the natural behavior and progression of precursor lesions
      towards invasive cancer, how to firmly establish the performance characteristics
      of EUS and MRI for the detection of (early) lesions in individuals at high risk
      for pancreatic cancer, and how to determine which lesions can be safely observed
      with continued surveillance and which lesions justify resection.

PMID- 21088420
TI  - What's new in therapy of pancreatic cancer?
AB  - BACKGROUND: Pancreatic cancer remains a dismal disease with a median survival
      after diagnosis of about 6 months. METHODS: Clinical trials with regard to
      treatment of pancreatic cancer, published as full manuscripts within the last 3
      years and available via PubMed, were evaluated. RESULTS: Several factors have
      positive influences on survival after pancreas resection: well-differentiated
      tumor grade, low tumor size, no duodenal or major vessel invasion, no perineural
      invasion, negative lymph node status, resection margin negativity (R0), high
      volume centers, presence of human equilibrative nucleoside transporter 1 in
      patients treated with gemcitabine, low preoperative tumor marker CA 19-9, and low
      bilirubin level. The following factors seem to have no influence on survival
      after pancreas resection: age, blood loss and transfusion requirements following
      resection, location of tumor, and type of resection. Adjuvant chemotherapy after
      R0 resection is standard: gemcitabine seems to be superior to 5-FU or no therapy.
      Nevertheless, only a few patients survive for at least 5 years after R0 resection
      and adjuvant chemotherapy. Most patients need palliative treatment. Besides best
      supportive care including nutritional support, therapy for pain and endoscopic
      treatment of jaundice, gemcitabine is standard in both locally advanced and
      metastatic disease. The addition of the tyrosine kinase inhibitor erlotinib
      prolongs median survival for only 2 weeks. Erlotinib has only beneficial effects
      in patients who develop a skin rash. None of the studied combinations of various
      therapies have demonstrated any additional benefits. CONCLUSION: There are no
      real medical breakthroughs with regards to improving the prognosis of pancreatic
      cancer.

PMID- 21088421
TI  - Adjuvant therapy in pancreatic cancer.
AB  - Pancreatic cancer is one of the major causes of cancer death in Europe with a 5
      year survival rate of less than 5%. Although surgery cannot guarantee a cure, the
      5-year survival does improve to around 10% following resection and increases to
      20-30% with adjuvant chemotherapy. The European Study Group for Pancreatic Cancer
      (ESPAC) 1 trial was the first adequately powered, randomized study to assess
      chemoradiotherapy (CRT), concurrent with 5-fluorouracil (5-FU) and chemotherapy
      [5-FU/folinic acid (FA)] in resected pancreatic cancer. There was a survival
      benefit for adjuvant chemotherapy, but not for adjuvant CRT. Adjuvant CRT also
      did not improve survival in the EORTC multicenter prospective randomized trial by
      Klinkenbijl et al. (1999). The phase 3 RTOG 9704 trial compared pre- and
      postchemoradiation gemcitabine to pre- and postchemoradiation 5-FU. Overall there
      was no difference in overall survival between the 2 arms. Adjuvant gemcitabine
      significantly improved disease-free survival and later overall survival compared
      to surgery alone in the CONKO-001 randomized trial. The ESPAC-3(v2) trial
      compared adjuvant gemcitabine versus 5-FU/FA. The final 2-year analysis
      demonstrated median survival from resection of patients treated with 5-FU/FA was
      23.0 months (95% CI: 21.1, 25.0) and 23.6 months (95% CI: 21.4, 26.4) for
      patients treated with gemcitabine. Further randomized studies will assess the
      role of adjuvant combination chemotherapy (ESPAC-4). The key to the future of
      adjuvant therapy in pancreatic cancer will be the identification of novel and
      effective agents, and better biomarker technology underpinned by translational
      research which will inform the design of future trials.

PMID- 21088422
TI  - Abdominal fat, adipose-derived hormones and mild cognitive impairment: the J
      SHIPP study.
AB  - BACKGROUND/AIM: Lower body weight in later life has been shown to be associated
      with dementia. However, abdominal fat distribution under conditions of mild
      cognitive impairment (MCI) and the possible involvement of leptin and adiponectin
      in MCI have not been fully investigated. METHODS: We analyzed 517 middle-aged-to
      elderly community-dwelling persons. Abdominal subcutaneous fat and visceral fat
      areas were determined using computed tomography, and plasma leptin and
      adiponectin concentrations were measured in fasting samples. MCI was assessed
      using the Japanese version of the MCI screening method. RESULTS: In men, the
      abdominal subcutaneous fat area was significantly lower in participants with MCI
      than in those with normal cognitive function [median (interquartile range): 107.4
      (85.9, 133.1) cm2 vs. 136.4 (93.1, 161.4) cm2; p = 0.002]. Logistic regression
      analyses with confounding factors including age and abdominal subcutaneous fat
      area showed that a 10 mg/l increase in plasma adiponectin had a protective effect
      against the development of MCI in men (odds ratio: 0.46; 95% CI: 0.20-0.97; p =
      0.041). In contrast, MCI was not found to be associated with abdominal fat area
      or adipose-derived hormones in women. CONCLUSION: Reduced amounts of subcutaneous
      fat and low levels of plasma adiponectin were found to be associated with MCI in
      men.

PMID- 21088424
TI  - Restless legs syndrome and pregnancy: follow-up of pregnant women before and
      after delivery.
AB  - AIMS: To describe the frequency of restless legs syndrome (RLS) in a French
      population of randomly selected women during their third trimester of pregnancy
      and its evolution up to 3 months after delivery and to identify potential factors
      associated with the improvement of RLS after delivery. METHODS: A cross-sectional
      questionnaire survey. RESULTS: 186 pregnant women living in a French town were
      included. 32% of women were affected by RLS during the third trimester of their
      pregnancy. Multiple pregnancies and iron intake during pregnancy were
      significantly associated with RLS during the third trimester. RLS disappeared
      after delivery among 64.8% of the women, and by less than 2 weeks after delivery
      in half of them. This improvement after delivery was not associated with the
      number of previous pregnancies, the RLS severity and iron intake during
      pregnancy, peridural anaesthesia, caesarean section, delivery complications,
      newborn weight, breastfeeding, dopaminergic agent intake after delivery, and with
      the absence of RLS before pregnancy. CONCLUSIONS: RLS affects one third of
      pregnant women during their third trimester and usually improves after delivery.
      Although there is no allowed treatment, most of the time only counselling and
      iron status assessment should be provided.

PMID- 21088425
TI  - Non-sentinel lymph node status and prognosis of breast cancer patients with
      micrometastatic sentinel lymph nodes.
AB  - BACKGROUND: The prognostic significance of sentinel lymph node (SLN)
      micrometastases and the need for axillary lymph node dissection (ALND) on
      patients with micrometastases in SLNs remain controversial. METHODS: A
      prospective database of 657 breast cancer patients who underwent SLN biopsy
      (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue
      dye and small-sized technetium-99m-labeled tin colloid. RESULTS: Micrometastases
      in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50
      patients with micrometastatic SLNs underwent ALND and no further metastases were
      found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic
      SLNs who decided to forego ALND, no axillary lymph node recurrence has been
      observed during a median follow-up time of 47 months. There is no significant
      difference in recurrence-free survival between the patients with micrometastatic
      and negative SLNs (p = 0.90). CONCLUSIONS: These data suggest that it may not be
      necessary to perform ALND on patients with micrometastases in SLNs and that the
      presence of micrometastases in SLNs may not be associated with prognosis.

PMID- 21088426
TI  - Improved outcome after 'bottom-up' immunosuppression in liver transplant
      recipients with preoperative renal impairment.
AB  - BACKGROUND: Most patients with high MELD scores have impaired renal function
      prior to transplantation. PATIENT AND METHODS: A retrospective case control study
      was conducted with initial low immunosuppression, which was increased when
      patients rejected or were clinically stable beyond day 30 ('bottom-up'). RESULTS:
      Thirty patients with impaired renal function were included. Fifteen were treated
      with de novo cyclosporine A (CsA; group A), and 15 had 'bottom-up'
      immunosuppression (group B). Baseline renal function was similar: serum
      creatinine (SCr) median 1.8 mg/dl (range: 1.5-4.0 mg/dl; group A) versus 2.4
      mg/dl (range: 1.5-4.0 mg/dl; group B; p = 0.24). The requirement for renal
      replacement therapy was significantly lower in group B (p = 0.032). Ten received
      'bottom-up' immunosuppression [4 CsA/1 sirolimus (Sir) 'on demand' after
      rejection, 5 Sir (stable)] beyond day 30. By months 6 and 12 (1.6 mg/dl vs. 1.2
      mg/dl), SCr values were significantly better in group B (p = 0.006). Renal
      function in group B did not differ between patients receiving CsA or Sir. Overall
      complication rates, survival and biopsy-proven acute rejection were similar,
      although BANFF scores were higher in group B (p = 0.004). CONCLUSION: Successful
      implementation of 'bottom-up' immunosuppression in liver transplant recipients
      with high lab-MELD scores and renal dysfunction at the time of transplantation
      has the potential to substantially improve short- and long-term outcomes.

PMID- 21088427
TI  - Long-term phonatory instability in ataxic dysarthria.
AB  - AIMS: Long-term phonatory instability can be quantified using cyclical and
      noncyclical measures. The objective of this study is to evaluate phonation in
      ataxic dysarthria and a control group of normal speakers to answer two main
      questions: (1) How common is elevated cyclical and noncyclical instability in
      ataxic dysarthria compared to that in a normal control group? (2) Is cyclical
      instability predictive of noncyclical instability? METHODS: Vowel prolongations
      of ataxic-dysarthric and normal speakers were compared using the Motor Speech
      Profile module of the Computerized Speech Lab. Cyclical measures included tremor
      rate, amplitude and periodicity. Noncyclical measures included the coefficient of
      variation for loudness and frequency. RESULTS: Noncyclical measures are elevated
      in a subset of speakers with ataxic dysarthria regardless of whether cyclical
      instability (vocal tremor) is present. Cyclical instability was detected in
      nearly half the patients. Interestingly, elevations in both types of measures
      also described phonation of a number of the participants in the control group.
      CONCLUSION: Combined use of cyclical and noncyclical measures can document
      aspects of phonation in ataxic dysarthria that have clinical implications.

PMID- 21088428
TI  - Perspectives in microvascular fluid handling: does the distribution of
      coagulation factors in human myocardium comply with plasma extravasation in
      venular coronary segments?
AB  - BACKGROUND: Heterogeneity of vascular permeability has been suggested for the
      coronary system. Whereas arteriolar and capillary segments are tight, plasma
      proteins pass readily into the interstitial space at venular sites. Fittingly,
      lymphatic fluid is able to coagulate. However, heart tissue contains high
      concentrations of tissue factor, presumably enabling bleeding to be stopped
      immediately in this vital organ. The distribution of pro- and anti-coagulatively
      active factors in human heart tissue has now been determined in relation to the
      types of microvessels. METHODS AND RESULTS: Samples of healthy explanted hearts
      and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin
      was found throughout the interstitial space. Tissue factor was packed tightly
      around arterioles and capillaries, whereas the tissue surrounding venules and
      small veins was practically free of this starter of coagulation. Thrombomodulin
      was present at the luminal surface of all vessel segments and especially at
      venular endothelial cell junctions. Its product, the anticoagulant protein C,
      appeared only at discrete extravascular sites, mainly next to capillaries. These
      distribution patterns were basically identical in the healthy and diseased
      hearts, suggesting a general principle. CONCLUSIONS: Venular extravasation of
      plasma proteins probably would not bring prothrombin into intimate contact with
      tissue factor, avoiding interstitial coagulation in the absence of injury.
      Generation of activated protein C via thrombomodulin is favored in the vicinity
      of venular gaps, should thrombin occur inside coronary vessels. This
      regionalization of distribution supports the proposed physiological heterogeneity
      of the vascular barrier and complies with the passage of plasma proteins into the
      lymphatic system of the heart.

PMID- 21088429
TI  - Genotyping of AAV plasmid stocks: quality control in adeno-associated virus
      vector production.
AB  - Recombinant adeno-associated virus (rAAV) vectors are a promising tool for gene
      therapy. When multiple serotypes are handled in the same laboratory during the
      AAV vector production, it is essential to have means to identify the serotype in
      a sample and to confirm the absence of cross-contaminating AAV sequences in
      plasmid stocks as well as end products. Here, we describe the development of a
      Multiplex AAV Genotyping (MAG) assay to type sensitively and specifically DNA
      from AAV serotypes 1-12 and to detect AAV2 serotype DNA sequences encoding
      peptide insertions used to modify tissue tropism. MAG is based on multiplex PCR
      using type-specific primers and subsequent multiplex hybridization by Luminex.
      The assay is highly specific, and can easily identify plasmid cross
      contaminations. Using 10-fold dilution series, the detection limit was below 10
      AAV genomes per PCR. In artificial cross-contamination experiments with a 1,000
      fold excess of one AAV serotype versus another one, the contaminating type could
      be still detected with 10-100 AAV genomes. In a first application, MAG identified
      successfully cross-contaminated AAV plasmid stocks. In conclusion, MAG is a
      powerful high-throughput tool in assessing the purity and identity of AAV DNA
      plasmids and other starting materials used for AAV vector production.

PMID- 21088430
TI  - Virtual reality in pediatric neurorehabilitation: attention deficit hyperactivity
      disorder, autism and cerebral palsy.
AB  - This paper presents the current status and use of virtual reality (VR) for
      children with attention deficit hyperactivity disorder (ADHD), autism and
      cerebral palsy. This literature review explores how VR systems have been used as
      treatment tools to address the primary impairments of these disorders. Three
      major classes of VR display systems are identified that can be characterized by
      the type of human-computer interaction provided: (1) feedback-focused
      interaction, (2) gesture-based interaction, and (3) haptic-based interaction. The
      demonstrated effectiveness and potential effectiveness of each class are
      discussed in the context of remediating the primary impairments of children with
      ADHD, autism and cerebral palsy. Three major themes for future research are
      discussed to support continued research interest in using VR in pediatric
      neurorehabilitation.

PMID- 21088431
TI  - A systematic review of the incidence and prevalence of long-term neurological
      conditions in the UK.
AB  - BACKGROUND: Updated, robust estimates of the incidence and prevalence of rare
      long-term neurological conditions in the UK are not available. Global estimates
      may be misrepresentative as disease aetiology may vary by location. OBJECTIVES:
      To systematically review the incidence and prevalence of long-term neurological
      conditions in the UK since 1988. SEARCH STRATEGY: Medline (January 1988 to
      January 2009), Embase (January 1988 to January 2009), CINAHL (January 1988 to
      January 2009) and Cochrane CENTRAL databases. SELECTION CRITERIA: UK population
      based incidence/prevalence studies of long-term neurological conditions since
      1988. Exclusion criteria included inappropriate diagnoses and incomprehensive
      case ascertainment. DATA COLLECTION AND ANALYSIS: Articles were included based on
      the selection criteria. Data were extracted from articles with ranges of
      incidence and prevalence reported. MAIN RESULTS: Eight studies met the criteria
      (3 on motor neurone disease; 4 on Huntington's disease; 1 on progressive
      supranuclear palsy). The incidence of motor neurone disease ranged from 1.06 to
      2.4/100,000 person-years. The prevalence ranged from 4.02 to 4.91/100,000. The
      prevalence of Huntington's disease ranged from 4.0 to 9.94/100,000. The
      prevalence of progressive supranuclear palsy ranged from 3.1 to 6.5/100,000.
      CONCLUSIONS: The review updates the incidence/prevalence of long-term
      neurological conditions. Future epidemiological studies must incorporate
      comprehensive case ascertainment methods and strict diagnostic criteria.

PMID- 21088432
TI  - Can mortality data be used to estimate amyotrophic lateral sclerosis incidence?
AB  - BACKGROUND: Because studies of the incidence of amyotrophic lateral sclerosis
      (ALS) have uncertain feasibility and high costs, mortality rates are often used
      to provide an estimate. We performed a systematic review of the literature
      concerning mortality related to ALS. We aimed to use well-known criteria of good
      epidemiological practice to assess the methodological quality of the studies.
      METHODS: A Medline and ScienceDirect literature search was performed to identify
      studies on ALS mortality published from 1971 to 2009. The literature was examined
      following 6 criteria. RESULTS: Of the 29 studies examined, almost all presented a
      clear definition of the population at risk, but 55% of the papers did not report
      on the accuracy of death certificates, and the use of both 'underlying' and
      'contributory' causes of death was identified in only 41% of cases. When
      comparing ALS mortality data between calendar dates, the codes from the
      International Classification of Diseases were consistent overall, except in 3
      studies. A majority of articles that compared mortality patterns between
      geographical regions or ethnic groups discussed the key issues of comparability
      of health care and equality of access. Overall, among the 29 ALS mortality
      studies, only 3 complied with all the criteria. In 2 of them, the mortality rates
      were highly consistent with available incidence data. CONCLUSION: Only few
      studies on mortality data followed a high-quality methodology. When studies
      complied with the criteria, they showed good accuracy with regard to incidence
      rates. The criteria used in this study could also be used to guide future studies
      based on mortality data.

PMID- 21088433
TI  - Reducing global neonatal mortality is possible.
AB  - BACKGROUND: The global neonatal mortality of 28/1,000 live births is unacceptably
      high. Furthermore, the huge difference in mortality between high- and low-income
      countries and regions is presently one of the most burning human rights issues.
      The decline in neonatal mortality has been slow and is a main reason the
      Millennium Development Goal 4 does not seem to have been reached. OBJECTIVES:
      Several countries have shown it is possible to reduce neonatal mortality quickly
      and dramatically without much cost. METHODS: It is important to learn from the
      successful countries and focus on the 3-4 major causes of neonatal death:
      asphyxia, infection, low birth weight/prematurity and congenital malformations.
      RESULTS: A reasonable short-term goal is to reduce global neonatal mortality to
      15/1,000 which can be achieved without introduction of high technology medicine.
      A further reduction of mortality to 5/1,000 should be the next global goal.
      Reaching this would reduce the present 3.8 million annual deaths by 3 million. In
      order to do this, regionalization of health care should be implemented. Maternal
      health should be the focus, with free antenatal care and centralized deliveries
      with health personnel attending the birth. Education of girls is perhaps the best
      way to prevent perinatal and neonatal deaths. Ten simple recommendations are
      given to reduce neonatal mortality. One of these is that each newborn baby in the
      world should have free access to essential drugs. CONCLUSIONS: It is possible to
      reduce newborn mortality in all countries and regions. Most important to achieve
      these goals is, however, political will.

PMID- 21088434
TI  - Survival in congenital diaphragmatic hernia: use of predictive equations in the
      ECMO population.
AB  - BACKGROUND: Equations have been proposed by the Wilford Hall/Santa Rosa (WHSR)
      and Congenital Diaphragmatic Hernia Study Group (CDHSG) for predicting survival
      in patients with CDH. The CDHSG stratifies risk based on a logistic regression
      equation incorporating birth weight and 5-min Apgar score, while the WHSR group
      uses the difference between maximum pO(2) and maximum pCO(2) as an index of risk.
      These models have not been applied specifically to the CDH ECMO (extracorporeal
      membrane oxygenation) population, a group at highest mortality risk. OBJECTIVES:
      To evaluate the WHSR and CDHSG predictive equations when applied to a population
      of patients with CDH requiring ECMO life support. METHODS: A single-center
      retrospective review was conducted on infants with CDH treated with ECMO between
      1993 and 2007. Predicted and actual outcomes were compared using receiver
      operating curve (ROC) analyses in which an area under the curve (AUC) of 1
      denotes 100% agreement between predicted and actual outcomes. Kaplan-Meier
      analyses were also used to compare survival of patients who were risk-categorized
      according to each prediction model. Minimum pre-ECMO pCO(2) was likewise
      evaluated as a predictor of survival. RESULTS: Overall survival was 50% in 62 CDH
      patients treated with ECMO during the study period. The CDHSG equation did not
      discriminate between survivors and nonsurvivors (AUC 0.55, p = 0.499). The
      modified WHSR formula showed better discrimination of survival (AUC 0.71, p =
      0.004). Lowest achievable pre-ECMO pCO(2) had the highest AUC (0.723, p = 0.003).
      Patients with minimum pre-ECMO pCO(2) <50 mm Hg had 56% survival, while those
      with >70 mm Hg had 0% survival. CONCLUSIONS: Equations proposed to predict
      survival in CDH patients may not discriminate survivors from nonsurvivors in the
      ECMO population. In this highest risk group, factors such as birth weight and
      Apgar score are less critical in estimating mortality risk than indicators of
      ventilation and oxygenation that reflect the degree of pulmonary hypoplasia.

PMID- 21088435
TI  - The immunomodulatory effect of the antidepressant sertraline in an experimental
      autoimmune encephalomyelitis mouse model of multiple sclerosis.
AB  - BACKGROUND: We have previously demonstrated the immunomodulatory activity of some
      selective serotonin reuptake inhibitors. OBJECTIVES: In this research, we
      performed an in vivo/ex vivo study to evaluate the potential immunosuppressive
      effect of sertraline in an experimental autoimmune encephalomyelitis (EAE) model
      of multiple sclerosis. METHODS: Mice (C57/bl EAE) were treated with sertraline (5
      mg/kg) or dexamethasone (1 mg/kg) 7 days after EAE induction and then 3 times
      weekly (for 3 weeks). RESULTS: Sertraline modestly improved the clinical score of
      EAE and attenuated the disease-induced weight loss. Sertraline also significantly
      decreased ex-vivo splenocyte viability, proliferation and secretion of pro
      inflammatory cytokines in EAE mice. CONCLUSIONS: We suggest that sertraline might
      be an add-on option for multiple sclerosis treatment.

PMID- 21088436
TI  - Does the metastatic lymph node ratio influence the disease-free survival of
      patients with breast cancer: single-center experiences.
AB  - BACKGROUND: Axillary lymph nodes (ALNs) are the most important prognostic factor
      for survival in breast cancer. Pathological evaluation can affect the number of
      involved lymph nodes. In the current study, we evaluated whether the metastatic
      lymph node ratio (n ratio) is important in predicting disease-free survival (DFS)
      for breast cancer patients. MATERIAL AND METHODS: From 802 breast cancer cases,
      427 patients with ALN metastasis were analyzed retrospectively. The n ratio was
      categorized as n ratio 1 (1-10%), n ratio 2 (10.01-50%) and n ratio 3 (>50%). DFS
      was established according to the Kaplan-Meier method. Predicting risk factors for
      relapse were analyzed using the Cox proportional hazards model. RESULTS: The n
      ratio was significantly higher in breast cancer patients with advanced pathologic
      pT, pN and clinical stage, undifferentiated histology, lymphovascular and
      extracapsular invasion, more resected ALNs and positive progesterone receptor. In
      the univariate analysis, multicentricity, necrosis, grade, pN stage, estrogen
      receptor and progesterone receptor positivity, trastuzumab and neoadjuvant
      chemotherapy usage, the presence of inflammatory breast cancer and n ratio were
      found to be important factors in predicting DFS. Multivariate analysis indicated
      that multicentricity, neoadjuvant chemotherapy, trastuzumab usage and n ratio
      were significantly associated with prognosis. CONCLUSIONS: The n ratio is
      inexpensive, easily available and a simple prognostic factor for breast cancer
      patients with positive ALNs.

PMID- 21088437
TI  - Assessment of fatigue in cancer patients and community dwellers: validation study
      of the Filipino version of the brief fatigue inventory.
AB  - OBJECTIVE: Clinical trials that might identify effective therapies for cancer
      related fatigue, one of the most distressing symptoms experienced by patients,
      require a validated fatigue assessment tool. We developed and validated a
      Filipino language version of the Brief Fatigue Inventory (BFI-F) for describing
      the prevalence and severity of fatigue among Filipino patients with cancer.
      METHODS: We conducted a cross-sectional study in Manila, Philippines, in 206
      patients with cancer and 170 age-matched community-dwelling adults who had never
      had a diagnosis of cancer. Validity and reliability were evaluated by principal
      factor analysis and Cronbach's alpha coefficients. RESULTS: Factor analysis
      extracted 1 factor, i.e. fatigue severity, with a Cronbach's alpha of 0.95; this
      is consistent with the original BFI English version validation study.
      Approximately 49% of the patients with cancer had mild fatigue, 34% had moderate
      fatigue, and 17% had severe fatigue. Patients with a poorer performance status
      had significantly worse fatigue than patients with a better performance status
      (5.0 +/- 2.8 vs. 3.8 +/- 2.2; p < 0.05). Compared with community adults, the
      patients with cancer reported significantly higher levels of fatigue.
      CONCLUSIONS: The BFI-F had satisfactory internal consistency and validity, and it
      was able to measure the severity of fatigue and its influence on Filipino cancer
      patients.

PMID- 21088438
TI  - Bevacizumab plus irinotecan-based regimens in the treatment of metastatic
      colorectal cancer.
AB  - OBJECTIVES: Bevacizumab is a monoclonal antibody that directly inhibits vascular
      endothelial growth factor, a key regulator of angiogenesis. Bevacizumab
      significantly improves progression-free and/or overall survival in metastatic
      colorectal cancer in combination with standard chemotherapy. This review
      describes the evolution of irinotecan-based regimens for metastatic colorectal
      cancer and evaluates the addition of bevacizumab to these regimens. METHODS:
      Literature searches from large publication databases (PubMed, ASCO, ASCO GI,
      ESMO) were performed to capture key data relevant to bevacizumab, irinotecan, and
      the treatment of colorectal cancer. RESULTS: Data from numerous large,
      multinational studies support the addition of bevacizumab to irinotecan
      containing chemotherapy regimens for further improvement in patient outcomes. In
      a randomized, placebo-controlled trial, addition of bevacizumab to irinotecan
      significantly improved progression-free survival, overall survival and response
      rate in patients with metastatic colorectal cancer, and these results are
      supported by a number of other clinical trials and observational studies.
      Furthermore, the addition of bevacizumab to irinotecan improves outcomes
      regardless of K-ras mutational status. Bevacizumab has a well-established safety
      profile and the toxicities associated with its use are usually mild in severity
      and easily manageable. CONCLUSIONS: Addition of bevacizumab to irinotecan
      containing regimens is an effective therapy option for the treatment of
      metastatic colorectal cancer.

PMID- 21088439
TI  - A single-arm phase II trial of first-line paclitaxel in combination with
      lapatinib in HER2-overexpressing metastatic breast cancer.
AB  - INTRODUCTION: Lapatinib, an orally active tyrosine kinase inhibitor of epidermal
      growth factor receptor ErbB1 (EGFR) and ErbB2 (HER2), has activity as monotherapy
      and in combination with chemotherapy in HER2-overexpressing metastatic breast
      cancer (MBC). METHODS: This phase II single-arm trial assessed the safety and
      efficacy of first-line lapatinib in combination with paclitaxel in previously
      untreated patients with HER2-overexpressing MBC. The primary endpoint was the
      overall response rate (ORR). Secondary endpoints were the duration of response
      (DoR), time to response, time to progression, progression-free survival (PFS),
      overall survival, and the incidence and severity of adverse events. All endpoints
      were investigator- and independent review committee (IRC)-assessed. RESULTS: The
      IRC-assessed ORR was 51% (29/57 patients with complete or partial response) while
      the investigator-assessed ORR was 77% (44/57). As per the IRC, the median DoR was
      39.7 weeks, and the median PFS was 47.9 weeks. The most common toxicities were
      diarrhea (56%), neutropenia (44%), rash (40%), fatigue (25%), and peripheral
      sensory neuropathy (25%). CONCLUSIONS: First-line lapatinib plus paclitaxel for
      HER2-overexpressing MBC produced an encouraging ORR with manageable toxicities.
      This combination may be useful in first-line treatment for patients with HER2
      overexpressing MBC and supports the ongoing evaluation of this combination as
      first-line therapy in HER2-overexpressing MBC.

PMID- 21088440
TI  - Changes of tear film function after pterygium operation.
AB  - OBJECTIVE: To assess changes of tear film function in patients with pterygium
      after pterygium excision combined with limbal-conjunctival autograft
      transplantation. METHODS: Sixty eyes of 60 patients were entered in the study.
      The Schirmer test, tear breakup time (BUT) and mucus fern test (MFT) were
      evaluated in the patients before and after pterygium excision combined with
      limbal-conjunctival autograft transplantation. RESULTS: Compared with the
      opposite healthy eyes, the BUT and MFT in the eyes with pterygium were
      significantly different before the operation (p < 0.05); however, there was no
      significant difference in the results of the Schirmer test (p > 0.05). The
      results of the BUT and MFT in the eyes with pterygium were significantly
      different before and 4 weeks after the operation (p < 0.05). The BUT was
      prolonged from 9.89 +/- 3.95 to 12.78 +/- 4.12 s, and the ratio of normal
      crystallization in the MFT increased from 46.7 to 80.0%. There was no significant
      difference in the Schirmer test results before and after the operation (p >
      0.05). CONCLUSION: Tear functions were abnormal in the eyes with pterygium.
      Pterygium excision combined with limbal-conjunctival autograft transplantation
      can partially restore the tear film function into normal state, and the tear film
      function was stable 4 weeks after surgery.

PMID- 21088441
TI  - Developmental factors of fibrous opacification in the atopic cataract lens
      capsule.
AB  - AIM: We investigated the developmental factors of fibrous opacification in the
      atopic cataract lens capsule. METHOD: We examined the expression of transforming
      growth factor (TGF)-beta signals (phosphorylated Smad2/3 and Smad7) and
      plasminogen activator inhibitor (PAI)-1 in atopic cataract lenses by
      immunohistochemistry. The PAI-1 concentration in aqueous humor was also measured.
      RESULTS: Lens epithelial cells of the atopic cataract lens capsule showed
      positive immunohistochemical staining for phosphorylated Smad2/3 and Smad7. Lens
      epithelial cells of the age-related cataract lens capsule were positive for
      phosphorylated Smad2/3, but negative for Smad7 by immunohistochemistry. All cells
      were negative for PAI-1. However, high concentrations of PAI-1 were detected in
      the aqueous humor of atopic cataract patients. CONCLUSION: We suggest that TGF
      beta and PAI-1 contribute to fibrous opacification in the atopic cataract lens
      capsule.

PMID- 21088442
TI  - Variants of the adenosine A(2A) receptor gene are protective against
      proliferative diabetic retinopathy in patients with type 1 diabetes.
AB  - AIMS: The adenosine A(2A) receptor (ADORA(2A)) may ameliorate deleterious
      physiologic effects associated with tissue injury in individuals with diabetes.
      We explored associations between variants of the ADORA(2A) gene and proliferative
      diabetic retinopathy (PDR) in a cohort of patients with type 1 diabetes (T1D).
      METHODS: The participants were from the Pittsburgh Epidemiology of Diabetes
      Complications prospective study of childhood-onset T1D. Stereoscopic photographs
      of the retinal fundus taken at baseline, then biennially, for 10 years were used
      to define PDR according to the modified Airlie House system. Two tagging single
      nucleotide polymorphisms (tSNPs; rs2236624-C/T and rs4822489-G/T) in the
      ADORA(2A) gene were selected using the HapMap (haplotype map) reference database.
      RESULTS: A significant association was observed between SNP rs2236624 and PDR in
      the recessive genetic model. Participants homozygous for the T allele displayed a
      decreased risk of developing prevalent PDR (odds ratio, OR = 0.36; p = 0.04) and
      incident PDR (hazard ratio = 0.156; p = 0.009), and for all cases of PDR combined
      (OR = 0.23; p = 0.001). The protective effect of T allele homozygosity remained
      after adjusting for covariates. Similarly, for SNP rs4822489, an association
      between PDR and T allele homozygosity was observed following covariate adjustment
      (OR = 0.55; 95% CI: 0.31-0.92; p = 0.04). CONCLUSION: Genetic variants of
      ADORA(2A) offer statistically significant protection against PDR development in
      patients with T1D.

PMID- 21088443
TI  - Acute spiral ganglion cell degeneration following acoustic overstimulation: an
      experimental study.
AB  - BACKGROUND: To evaluate acoustic overstimulation-induced spiral ganglion cell
      (SGC) degeneration, and determine the relationship between the duration of
      acoustic overstimulation and rate of SGC degeneration. METHODS: Fifteen guinea
      pigs were randomized equally to 4 experimental groups, which were exposed to
      different durations (7.5, 15, 30 and 60 min) of acoustic overstimulation (120 dB
      at 4 kHz), and a control group. Every bulla was examined histopathologically and
      immunohistochemically. A quantitative and statistical analysis of acidophilic and
      TUNEL-positive SGCs was performed. RESULTS: In the control group, 2.1% of SGCs
      were acidophilic and no TUNEL-positive SGC was detected. In contrast, a
      statistically significant number of acidophilic (p = 0.000) and TUNEL-positive
      SGCs (p = 0.002) was determined in the experimental groups. Moreover, a positive
      correlation between the duration of acoustic overstimulation and acidophilic SGCs
      (p = 0.000), and a statistically significant relationship between the duration of
      acoustic overstimulation and TUNEL-positive SGCs (p = 0.000) were demonstrated.
      CONCLUSION: Acoustic overstimulation may induce acute SGC degeneration. A
      positive correlation was determined between the duration of acoustic
      overstimulation and rate of degenerated SGCs.

PMID- 21088444
TI  - Aspirin increases apolipoprotein-A-I-mediated cholesterol efflux via enhancing
      expression of ATP-binding cassette transporter A1.
AB  - BACKGROUND: The efflux of cellular cholesterol mediated by apolipoprotein (apo)A
      I and ATP-binding cassette transporter A1 (ABCA1) is a major pathway of reverse
      cholesterol transport. We investigated the effect of aspirin on this process.
      METHODS: The expression levels of ABCA1 in RAW264.7 cells were determined using
      reverse transcription polymerase chain reaction and Western blot analysis. 3H
      cholesterol efflux was measured by scintillation counting. RESULTS: 0.5 mmol/l
      aspirin increased apoA-I-mediated cholesterol efflux and increased the expression
      of ABCA1. By increasing the dose of aspirin higher than 0.5 mmol/l, ABCA1
      expression and function were significantly decreased. In cells transfected with a
      specific peroxisome proliferator-activated receptor (PPAR)-alpha small
      interfering RNA, the induction of ABCA1 expression and apoA-I-mediated 3H
      cholesterol efflux by aspirin were substantially suppressed. CONCLUSIONS: The
      data demonstrate that low-dose aspirin increases ABCA1 expression via a PPAR
      alpha-dependent mechanism and increases apoA-I-mediated cholesterol efflux.

PMID- 21088445
TI  - Double standards in psychotherapy research.

PMID- 21088446
TI  - The emperor's new clothes - comment on Bhar et al.

PMID- 21088448
TI  - Carbon-dioxide-induced flashback in a healthy man with a history of near
      drowning.

PMID- 21088449
TI  - Antidepressant-induced tardive dysphoria.

PMID- 21088450
TI  - Predictors of mental health and quality of life after liver transplantation.

PMID- 21088451
TI  - Reduced cardiac autonomic flexibility associated with medically unexplained
      somatic complaints in the context of internalizing symptoms in a preadolescent
      population sample: the TRAILS Study.

PMID- 21088452
TI  - Transdermal estradiol and testosterone transfer in man: existence, models, and
      strategies for prevention.
AB  - BACKGROUND: Transdermal hormone application allows delivery of a clinically
      relevant hormone dose often with fewer systemic side effects than oral
      formulations. However, transdermal hormone transfer from a dosed individual to
      naive interpersonal contact occurs and may cause significant hormone imbalance
      and adverse effects. METHODS: We reviewed PubMed, Medline, and Scopus articles
      from the years 1950 to 2010 for articles related to transdermal hormone transfer
      in the setting of in vivo and in vitro human and animal models. We used the
      following key words: transfer, transdermal, absorption, cutaneous, hormone,
      estradiol, and testosterone. Unpublished trials were reviewed on the US Food and
      Drug Administration (FDA) website for product approval. RESULTS: Data reflecting
      in vivo transfer of transdermal estradiol and testosterone in man is available
      from case reports, clinical trials, and FDA product information. While results
      clearly show that transfer can occur, methods for measuring the effect are not
      standardized and are thus difficult to compare among positive and negative
      studies. No in vitro human studies or animal models have been developed to
      specifically examine transfer potential of transdermal estradiol or testosterone.
      CONCLUSION: It is necessary to consider the mechanism behind transdermal hormone
      transfer and consider ways to enhance clinical benefits to the dosed individual
      while minimizing transfer to a naive interpersonal contact. A detailed discussion
      of trial comparisons and future optimization methods may help enhance our
      understanding of the potential for transdermal hormone transfer and encourage
      development of newer formulations and/or application methods to minimize its
      occurrence.

PMID- 21088453
TI  - Supplementation of flaxseed oil diminishes skin sensitivity and improves skin
      barrier function and condition.
AB  - BACKGROUND: Skin sensitivity is a common problem in the Western population
      correlated with changes of skin properties like skin barrier function, hydration
      and skin physiology. Skin properties can be modulated by dietary fatty acids
      (FA), especially poly-unsaturated FA. The present study was performed to evaluate
      the effect of daily supplementation with flaxseed oil and safflowerseed oil on
      healthy volunteers with sensitive skin. METHODS: The study was designed as a
      randomized, double-blind 12-week intervention with 2 female treatment groups (n =
      13). Plasma FA profile, skin sensitivity, skin hydration, transepidermal water
      loss (TEWL) and skin surface were evaluated on day 0, week 6 and week 12.
      RESULTS: Supplementation with flaxseed oil led to significant decreases in
      sensitivity (after nicotinate irritation), TEWL, skin roughness and scaling,
      while smoothness and hydration were increased. Concomitantly, the ratio of n-6/n
      3 FA in plasma decreased. Upon supplementation with safflowerseed oil, only a
      significant improvement in skin roughness and hydration was observed; however,
      the effects were less pronounced and determined at a later point in time than
      with flaxseed oil. The plasma n-6/n-3 FA ratio increased. CONCLUSION: The data
      provide evidence that daily intake of flaxseed oil modulates skin condition.

PMID- 21088454
TI  - Model of in vitro healing to test the influence of dedifferentiated Crithmum
      maritimum cells on dermal repair and epidermal regeneration.
AB  - BACKGROUND: The aim was to test the influence of dedifferentiated Crithmum
      maritimum cells (dCMC), totipotent vegetal stem cells, on epidermal regeneration
      in perfect homeostasis using a skin equivalent (SE) model. MATERIALS AND METHODS:
      SE are prepared by seeding fibroblasts on a collagen-glycosaminoglycan-chitosan
      dermal substrate (DS) epidermalized by keratinocytes 3 weeks later. The
      originality of this present study lies in the systemic administration of dCMC
      from the moment when fibroblasts are seeded in the DS right through to the
      reconstruction of the SE. The thickness of the epidermis as well as the number of
      proliferating cells expressing Ki-67 and layers expressing terminal
      differentiation marker (filaggrin) were compared in the dCMC-treated SE versus an
      untreated control group. RESULTS: dCMC accelerated the complete regeneration and
      differentiation of the epidermis compared to the negative control (35 days
      instead of 42 days). Histology showed a multilayered, thick and differentiated
      epithelium after 35 days of culture. The basal and suprabasal layers had
      increased 4.88 +/- 0.41 times versus the negative control (Mann-Whitney U test: p
      < 0.001). This result was attributed to the greater proliferation of basal cells
      because the cell numbers expressing the Ki-67 proliferation marker had increased
      significantly compared to the negative control (Mann-Whitney U test: p < 0.001).
      Moreover, dCMC allowed the differentiated epithelium to recover because only
      treated SE expressed the terminal differentiation marker filaggrin. CONCLUSION:
      Our data show that dCMC enhance epidermal cell grafts by stimulating their
      regeneration and differentiation in perfect homeostasis. They allow the epidermis
      to recover its structure for protective functions faster than the negative
      control.

PMID- 21088455
TI  - Characterization of skin friction coefficient, and relationship to stratum
      corneum hydration in a normal Chinese population.
AB  - BACKGROUND AND OBJECTIVES: Studies have demonstrated that some cutaneous
      biophysical properties vary with age, gender and body sites. However, the
      characteristics of the skin friction coefficient in different genders and age
      groups have not yet been well established. In the present study, we assess the
      skin friction coefficient in a larger Chinese population. METHODS: A total of 633
      subjects (300 males and 333 females) aged 0.15-79 years were enrolled. A
      Frictiometer FR 770 and Corneometer CM 825 (C&K MPA 5) were used to measure the
      skin friction coefficient and stratum corneum hydration, respectively, on the
      dorsal surface of the hand, the forehead and the canthus. RESULTS: In the
      females, the maximum skin friction coefficients on both the canthus and the
      dorsal hand skin were observed around the age of 40 years. In the males, the skin
      friction coefficient on the dorsal hand skin gradually increased from 0 to 40
      years of age, and changed little afterward. Skin friction coefficients on some
      body sites were higher in females than in age-matched males in some age groups.
      On the canthus and the dorsal hand skin of females, a positive correlation was
      found between skin friction coefficient and stratum corneum hydration (p < 0.001
      and p < 0.0001, respectively). In contrast, in males, the skin friction
      coefficient was positively correlated with stratum corneum hydration on the
      forehead and the dorsal hand skin (p < 0.05 and p < 0.0001, respectively).
      CONCLUSION: The skin friction coefficient varies with age, gender and body site,
      and positively correlates with stratum corneum hydration on some body sites.

PMID- 21088456
TI  - Simultaneous repair of chronic full-thickness rotator cuff tears during fixation
      of proximal humerus fractures and clinical results.
AB  - OBJECTIVES: We investigated the incidence of chronic rotator cuff tears
      encountered during fixation of proximal humerus fractures with locking plate
      screw systems, and evaluated the functional results of simultaneous surgical
      repair of these injuries. METHODS: A total of 111 patients underwent surgical
      treatment for proximal humerus fractures. Of these, nine patients (8 females, 1
      male; mean age 73 years; range 56 to 84 years) who had concomitant chronic full
      thickness rotator cuff tears were included in the study. According to the AO
      classification, the fractures were type 11A1 (12C1 also present) in one patient,
      11A2 (12C2 also present) in one patient, 11B1 in two patients, 11B2 in three
      patients, and 11C2 in two patients. None of the patients underwent preoperative
      magnetic resonance imaging. Fracture fixation was made with the PHILOS plate in
      five patients, and with the S3 Proximal Humerus Plate in four patients. All full
      thickness rotator cuff tears were detected during the operation. Following open
      reduction and internal fixation after a deltoid splitting incision, rotator cuff
      tears were repaired by primary suture in two patients, and with a suture anchor
      in seven patients. All the patients used a padded shoulder-arm sling for six
      weeks and received a standard rehabilitation program. All the patients were
      evaluated radiographically and functionally using the Constant-Murley shoulder
      score at postoperative 6 weeks, 6 months, and 12 months. The mean follow-up
      period was 17.3 months (range 8 to 30 months). RESULTS: The incidence of full
      thickness rotator cuff tears was 8.1%. All the patients had supraspinatus tears,
      which were accompanied by infraspinatus tears in three patients. The sizes of the
      tears were classified as large (between 3-5 cm) in three patients, intermediate
      (between 1-3 cm) in five patients, and small (<1 cm) in one patient. One patient
      had L-shaped, two patients had U-shaped, and six patients had C-shaped tears.
      None of the patients had healing problems or avascular necrosis. The mean
      Constant-Murley shoulder score was 85.4 (range 67 to 100). All the patients were
      satisfied with the results of surgical treatment. CONCLUSION: The integrity of
      the rotator cuff must be checked after reduction and fixation of proximal humerus
      fractures and, when present, the tears should be repaired simultaneously either
      primarily or with suture anchors. Simultaneous repair of rotator cuff tears does
      not negatively affect functional outcomes.

PMID- 21088457
TI  - Comparison between the results of open and arthroscopic repair of isolated
      traumatic anterior instability of the shoulder.
AB  - OBJECTIVES: The aim of this study was to compare the early postoperative results
      of open and arthroscopic Bankart repair for isolated traumatic anterior
      instability of the shoulder. METHODS: The study included 64 male patients who
      underwent surgery for traumatic recurrent anterior shoulder instability. Of
      these, 30 patients (mean age 25.1 years) underwent open Bankart repair and 34
      patients (mean age 25.8 years) underwent arthroscopic Bankart repair. All the
      patients had labral tears on preoperative magnetic resonance scans and had
      complaints of instability even during daily activities. Patients with at least
      six dislocations were included in the study; patients with multidirectional
      instability were excluded. The mean time from the first trauma to surgical
      intervention was 4.4 years (range 1 to 24 years) in the open surgery group, and
      3.8 years (range 1 to 17 years) in the arthroscopy group. Decision for surgical
      treatment was made based on limitation of activities because of fear of having a
      dislocation and on positive results of instability tests. Repair was performed
      using metal anchors in both groups. The clinical results were evaluated using the
      Rowe scale. The severity of pain on the first postoperative day was assessed
      using a visual analog scale (VAS). The mean follow-up period was 26.1 months
      (range 12 to 52 months) in the open surgery group, and 26.6 months (range 12 to
      51 months) in the arthroscopic repair group. RESULTS: The mean duration of
      operation was 2 hours for open surgery, and 2.5 hours for arthroscopic repair.
      The size of the incision was approximately 8 cm in the open surgery group, and 3
      cm in the arthroscopic repair group. The mean Rowe scores were 90.2 and 91.6,
      being higher in the arthroscopic repair group. Clinical results of open surgery
      were excellent in 21 patients (70%), good in eight patients (26.7%), and poor in
      one patient (3.3%). In the arthroscopic repair group, the results were excellent
      in 27 patients (79.4%), good in five patients (14.7%), and poor in two patients
      (5.9%). All the patients with a poor result experienced redislocations due to
      traumatic falls 5 to 18 months after surgery. The mean VAS score was 5.0 +/- 1.3
      in the open surgery group, and 4.4 +/- 1.3 in the arthroscopic repair group. Loss
      of external rotation was observed in 15 patients (20 degrees  in 8 patients, 10
      degrees  in 4 patients, 5 degrees  in 3 patients) in the open surgery group, and
      in nine patients (20 degrees  in 3 patients, 10 degrees  in 6 patients) in the
      arthroscopic repair group. There were no significant differences between the two
      groups with respect to Rowe scores, VAS scores, range of motion, apprehension
      test results, and the incidence of recurrent instability. CONCLUSION: Although,
      in the past, the results of arthroscopic repair were less satisfactory compared
      to open surgery, this condition has changed remarkably. The results of
      arthroscopic repair in our study were similar to those of open repair. We believe
      that, with enhanced experience and advances in arthroscopic repair techniques,
      arthroscopic treatment may outweigh open surgery.

PMID- 21088458
TI  - Reconstruction of shoulder abduction and external rotation with latissimus dorsi
      and teres major transfer in obstetric brachial plexus palsy.
AB  - OBJECTIVES: We evaluated the results of latissimus dorsi and teres major tendon
      transfer to the rotator cuff together with musculotendinous lengthening of the
      subscapularis and/or pectoralis major muscles in patients with internal rotation
      contracture and decreased external rotation and abduction secondary to
      obstetrical brachial plexus palsy. METHODS: Thirty patients (18 boys, 12 girls;
      mean age 9 years; range 4 to 15 years) with internal rotation contracture and
      loss of external rotation and abduction of the shoulder secondary to obstetrical
      brachial plexus palsy underwent transfer of the latissimus dorsi/teres major
      tendons to the rotator cuff. In addition, musculotendinous lengthening of the
      subscapularis and pectoralis major (n=15), pectoralis major (n=9), and
      subscapularis (n=6) were performed. Nine patients had upper plexus involvement
      (C5-6), 14 had C5-7 involvement, and seven had complete plexus involvement (C5
      T1). According to the Waters and Peljovich classification, all the patients had a
      congruent glenohumeral joint, which was classified as type 1 in one patient, type
      2 in 15 patients, and type 3 in 14 patients. Pre- and postoperative range of
      motion values of the patients were measured and their motor functions were
      evaluated with the Mallet scoring system. The mean follow-up period was 47.8
      months (range 9 to 84 months). RESULTS: Preoperatively, the mean active abduction
      was 75.8 degrees , and the mean active external rotation was 25.2 degrees .
      Postoperatively, the mean abduction and external rotation increased to 138.3
      degrees  (by 62.5 degrees , 82.5%) and 76.4 degrees (by 51.2 degrees , 203.2%),
      respectively. Improvements in the degrees of abduction and external rotation were
      significant (p=0.000). According to the Mallet scoring system, the mean
      preoperative global abduction and global external rotation scores were 2.97 and
      2.43, respectively; the mean Mallet scores for the ability to move the hand to
      the mouth, neck, and back were 2.50, 2.17, and 2.67, respectively.
      Postoperatively, the mean global abduction score increased to 3.97 (by 33.7%,
      p=0.000), and the mean global external rotation score increased to 3.77 (by
      55.1%, p=0.000). The mean scores for the ability to move the hand to the mouth,
      neck, and back were 3.30 (increased by 32%, p=0.000), 3.73 (increased by 71.9%,
      p=0.000), and 2.30 (decreased by 13.9%, p=0.003), respectively. Postoperative
      changes in the Mallet scores were all significant. Improvements in abduction and
      external rotation were not significant between patients <= 9 years and > 9 years
      of age (p > 0.05). CONCLUSION: Transfer of the latissimus dorsi and teres major
      tendons to the rotator cuff combined with musculotendinous lengthening of the
      subscapularis and/or pectoralis major provides satisfactory increases in shoulder
      abduction and external rotation, regardless of the age, in patients with no or
      minimal glenohumeral joint incongruency.

PMID- 21088459
TI  - Coracoclavicular ligament repair and screw fixation in acromioclavicular
      dislocations.
AB  - OBJECTIVES: We evaluated the long-term results of acromioclavicular dislocations
      treated with coracoclavicular fixation using a cancellous screw. METHODS:
      Coracoclavicular fixation was performed using the modified Bosworth technique in
      32 patients (24 males, 8 females; mean age 35 years; range 19 to 58 years) with
      acromioclavicular dislocations. According to the Rockwood classification, seven
      patients had type III, nine patients had type IV, 13 patients had type V, and
      three patients had type VI dislocations. Following repair of the coracoclavicular
      ligament, fixation was performed with a cancellous screw in all but two patients
      in whom a cortical screw was used. These two patients developed redislocation due
      to screw cut out and underwent reoperation with cancellous screw fixation and
      were not included in the final assessments. The screws were removed under local
      anesthesia after eight weeks postoperatively. The patients were evaluated for
      cosmetic appearance, functional status, pain, localized tenderness, articular
      range of motion, and with the functional Constant scoring system. The mean follow
      up was 3.1 years (range 1 to 8 years). RESULTS: The mean Constant score was 98
      (range 92 to 100). The results were excellent in 26 patients (86.7%) and good in
      four patients (13.3%). There was subluxation of the acromioclavicular joint in
      one patient (3.3%). The alignment of the acromioclavicular joint was normal in
      the remaining patients. None of the patients showed joint degeneration. All
      patients were pain-free and achieved full range of motion. CONCLUSION: With ease
      of application, low complication rate, and low rate of acromioclavicular joint
      arthrosis, the modified Bosworth technique is an effective surgical method in
      providing satisfactory shoulder function in acromioclavicular dislocations.

PMID- 21088460
TI  - The results of conservatively treated simple elbow dislocations.
AB  - OBJECTIVES: Closed reduction followed by short-time immobilization is the
      generally accepted treatment for simple elbow dislocations. However, the number
      of studies concerning the results of this method is limited. In this study, the
      clinical and radiographic results of conservatively treated simple elbow
      dislocations were retrospectively evaluated. METHODS: The study included 21
      patients (16 males, 5 females) who underwent closed reduction and immobilization
      for simple elbow dislocations. Simple dislocations were defined as non-fracture
      dislocations and dislocations accompanied by minor avulsion fractures that did
      not require additional surgery or immobilization. The mean age of the patients at
      the time of injury was 35 years (range 16 to 59 years). All the patients had
      posterior dislocations. Eleven patients (52.4%) had minor avulsion fractures.
      Following closed reduction, a plaster splint and hinged brace were used in four
      (19.1%) and 17 (81%) patients, respectively. Incremental active and passive
      motions were started at the end of the first week in patients in whom a brace was
      used. The mean duration of brace use was 27 +/- 16 days. Patients using a plaster
      splint were immobilized for three weeks. The patients were assessed clinically
      with respect to range of motion, instability, and neurologic findings after a
      mean follow-up period of 34 months (range 12 to 99 months). Functional
      assessments included the Mayo Elbow Performance Score (MEPS) and the Broberg
      Morrey Functional Rating Index (BMFRI). Standard elbow anteroposterior and
      lateral radiographs were examined for concentric reduction and signs of
      degeneration and heterotopic ossification. RESULTS: Compared to the normal side,
      the degrees of flexion, extension, flexion arc, and pronation were significantly
      decreased in dislocated elbows (p<0.05), while the degrees of supination and
      rotational arc were similar. There was no muscular atrophy. Four patients (19.1%)
      had residual instability and six patients (28.6%) had mild to moderate
      neurological complaints that were primarily related to the ulnar nerve. Three
      patients complained of mild pain, and one patient complained of moderate pain at
      rest. Radiographic assessment showed mild degeneration in three patients (14.3%),
      and mild to moderate heterotopic ossification in 14 patients (66.7%). Patients
      with and without heterotopic ossification did not differ significantly with
      respect to the values of joint range of motion. The mean MEPS and BMFRI scores
      were 96.9 and 97.7, respectively. The scores of both systems were excellent in 20
      patients (95.2%) and moderate in one patient (4.8%). The majority of the patients
      (81%) reported complaints about their elbows including sensation of stiffness in
      the elbow, pain during strenuous work or sports activities, and limitation of
      movement. Only four patients (19.1%) reported a feeling of full recovery.
      CONCLUSION: Although closed reduction with short-term immobilization is a
      universally accepted method for simple elbow dislocations with excellent
      functional scores, it is associated with significant limitations in joint
      movements and a great majority of patients do not consider themselves fully
      recovered.

PMID- 21088461
TI  - The results of surgical treatment for posttraumatic heterotopic ossification and
      ankylosis of the elbow.
AB  - OBJECTIVES: Heterotopic ossification which may develop following elbow injuries
      or elbow surgery may result in complete loss of elbow functions. We evaluated the
      results of surgical treatment for ankylosis of the elbow due to posttraumatic
      heterotopic ossification. METHODS: The study included seven patients (6 males, 1
      female; mean age 36 years; range 23 to 55 years) who developed heterotopic
      ossification and ankylosis of the elbow joint following surgical treatment of
      high-energy fractures in the circumference of the elbow. Two patients had
      comminuted olecranon fractures and elbow luxation, and five patients had
      comminuted intra-articular distal humeral fractures. Three patients had open
      fractures. Involvement was in the right elbow in two patients, and in the left
      elbow in five patients. One patient was monitored and treated in the intensive
      care unit for head trauma for 22 days. Initially, six patients were treated with
      plate osteosynthesis and one patient with tension band wiring. Foci of
      heterotopic ossification were detected on the radiographs taken after a mean of
      24 days (range 20 to 32 days) following surgical treatment of fractures. The
      patients were followed-up with conventional radiography and scintigraphy for a
      mean of 11 months (range 7 to 15 months) before surgical treatment, during which
      functional loss in elbow joint movements deteriorated and ankylosis developed.
      All the patients had Hastings type IIIC ankylosis and poor Mayo elbow performance
      scores (mean score 50.7). A posterior incision was used in three patients, and a
      double-column incision was used in four patients. At surgery, the ulnar nerve and
      the lateral and medial collateral ligaments were preserved, and a posterolateral
      capsular release, removal of heterotopic ossification, purging of the olecranon
      fossa, and resection of the tip of the olecranon were performed. After completion
      of capsular release, cartilage pathologies were evaluated. Four patients were
      found to have no definite cartilage damage, whereas in three patients the joint
      cartilage was seriously damaged. At final controls, the patients were assessed
      with the Mayo elbow performance score. The mean follow-up period was 23.4 months
      (range 10 to 36 months). RESULTS: In all cases, the range of motion and stability
      of the elbow joint were controlled and were found to be complete and stable at
      the end of the operation. At final controls, the Mayo elbow performance scores
      were good in three patients, moderate in one patient, and poor in three patients.
      All the patients with a poor elbow score had severe joint cartilage damage
      intraoperatively. CONCLUSION: Patients who develop heterotopic ossification and
      ankylosis of the elbow following trauma or elbow surgery may benefit from removal
      of heterotopic ossification foci and elbow relaxation procedures provided that
      there is not severe damage to the articular cartilage.

PMID- 21088462
TI  - Comparison of palmar locking plate and K-wire augmented external fixation for
      intra-articular and comminuted distal radius fractures.
AB  - OBJECTIVES: This study was designed to compare the results of palmar locking
      plate and K-wire augmented external fixation in the treatment of intra-articular
      comminuted distal radius fractures. METHODS: The study included 30 patients with
      intra-articular comminuted distal radius fractures. Sixteen patients (11 men, 5
      women; mean age 49 +/- 16 years) underwent open reduction and palmar locking
      plate fixation, and 14 patients (11 men, 3 women; mean age 35 +/- 10 years)
      underwent closed reduction and K-wire augmented external fixation. In both
      groups, eight patients had accompanying injuries. According to the AO/ASIF
      classification, there were four C1, 10 C2, and two C3 fractures in the locking
      plate group, and three C1, eight C2, and three C3 fractures in the external
      fixation group. For functional assessment, joint range of motion and grip
      strength were measured. The patients were assessed using the Gartland-Werley
      scale. Subjective functional assessment was made using the QuickDASH scale. On
      final radiographs, the presence of osteoarthrosis in the radiocarpal joint was
      assessed according to the Broberg-Morrey criteria. The follow-up period was at
      least 12 months (26.1 +/- 6.1 months in the locking plate group, and 62.7 +/-
      16.8 months in the external fixation group). RESULTS: Wrist flexion (p=0.012) and
      supination (p=0.003) degrees at final follow-up were significantly greater in the
      locking plate group. Other range of motion parameters were similar in the two
      groups. On final radiographic measurements, there were no significant differences
      between the two groups with respect to losses in palmar angulation, radial
      length, and radial inclination, and change in ulnar variance. The mean Gartland
      Werley scores did not differ significantly (2.4 +/- 2.4 with plate fixation, and
      2.0 +/- 2.8 with external fixation; p>0.05). The results were excellent in 11
      patients (68.8%) and good in five patients (31.3%) with plate fixation. The
      results of external fixation were excellent in 11 patients (78.6%), good in two
      patients (14.3%), and moderate in one patient (7.1%). The mean QuickDASH scores
      and time to return to work were similar in patients treated with a locking plate
      and external fixator (QuickDASH score 2.4 +/- 3.0 and 2.9 +/- 5.4; 1.9 +/- 0.5
      months and 2.1 +/- 0.7 months, respectively; p>0.05). The mean loss of strength
      compared to the healthy side at final follow-up was 3% in the locking plate
      group, and 5% in the external fixation group. Radiographic findings of stage 1
      osteoarthrosis were observed in four patients (25%) in the plate group, and in 11
      patients (78.6%) in the external fixation group. There were no complications in
      the locking plate group. In the external fixation group, two patients (14.3%) had
      regional pain syndrome, three patients (21.4%) had superficial pin and wire tract
      infections, and one patient complained of adherence at entry sites of the
      fixator. Overall, nine patients (64.3%) expressed dissatisfaction with the
      external fixator. CONCLUSION: Our results showed no superiority between the two
      treatment methods with respect to objective and subjective tools of evaluation.
      Palmar locking plate fixation was associated with full patient satisfaction. K
      wire augmented external fixation can be used as a safe method in selected cases
      in which the severity of distal radius fracture would not allow palmar locking
      plate fixation.

PMID- 21088463
TI  - Clinical and functional outcomes and proprioception after a modified accelerated
      rehabilitation program following anterior cruciate ligament reconstruction with
      patellar tendon autograft.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical and functional
      outcomes and proprioceptive function in patients who received a modified
      accelerated rehabilitation program after anterior cruciate ligament (ACL)
      reconstruction with a patellar tendon (PT) graft. METHODS: The study included 38
      patients (33 men, 5 women; mean age 27.6 +/- 6.4 years; range 18 to 45 years) who
      underwent ACL reconstruction with a PT graft and participated in a modified
      accelerated rehabilitation program. Only six patients were athletes. Isokinetic
      strengths of concentric knee extension and flexion were measured with the Cybex
      isokinetic dynamometer, and static balance was tested with the Sport-KAT device.
      For proprioceptive assessment, active repositioning was measured at knee flexions
      of 40 degrees , 20 degrees , and 5 degrees  with an isokinetic dynamometer.
      Activity levels and subjective functional results were evaluated with the Tegner
      activity scale and Lysholm knee score, respectively. For objective functional
      testing, single leg hop, triple leg hop, and one-legged crossover hop tests were
      used. Knee stability was assessed with the Lachman test and anterior drawer test
      and knee range of motion was measured. The mean follow-up period was 16.2 +/- 9.8
      months. RESULTS: There was no graft failure during the follow-up. Twenty patients
      (52.6%) had hypoesthesia at the donor site and 15 patients (39.5%) had anterior
      knee pain. Before surgery, all the patients had positive results in the Lachman
      and anterior drawer tests. After surgery, the Lachman test was negative in 32
      patients (84.2%), while six patients (15.8%) had grade 1 laxity. The mean Lysholm
      knee score showed a significant increase postoperatively (p<0.001). The mean
      preoperative and postoperative Tegner activity scores were not significantly
      different (p>0.05). There were no significant differences in the range of motion
      between operated and uninjured extremities (p>0.05). The two extremities were
      similar in proprioception and balance (p>0.05). Isokinetic quadriceps muscle
      strength was significantly decreased in the operated extremity only in extension
      at 60 degrees /sec angular velocity (p<0.05). Other muscle strength measurements
      were similar in both extremities. The ratios of flexion/extension muscle strength
      were significantly greater in the involved extremity at all angular velocities
      (p<0.05). The mean performance scores of three functional tests were more than
      85% of the uninvolved extremity. All the patients returned to preinjury daily
      activities or sports activities in 6 to 12 months postoperatively. CONCLUSION: We
      had satisfactory clinical, proprioceptive, and functional results in achieving
      dynamic and static stability of the knee with the modified accelerated
      rehabilitation program after ACL reconstruction with a PT graft.

PMID- 21088464
TI  - The morphological features of the mediopatellar and lateral folds of the
      developing knee joint: a fetus cadaveric study.
AB  - OBJECTIVES: The aim of the study was to evaluate the morphological features of
      the mediopatellar and lateral folds in fetal knees in the absence of any exposure
      to certain stress factors such as exercise or trauma. METHODS: The study was
      performed in the knee joints of 15 fetuses (6 males, 9 females) obtained as
      spontaneous abortion material at 20-34 weeks of gestation. The mediopatellar and
      lateral folds of the fetuses were classified into eight subgroups according to
      the following morphological features: A- Absence of folds; B- Short vertical
      band; C- Long vertical band; D- Narrow horizontal band; E- Broad horizontal band;
      F- Horizontal band accompanied by a vertical band; G- Horizontal band without a
      vertical band; H- Fenestrated band. RESULTS: The synovial membrane, covering the
      infrapatellar fat pad and forming the alar folds, extended upwards and formed the
      medial and lateral horizontal folds that covered the inferior part of the
      posterior aspect of the patella. These horizontal folds were thicker in the lower
      parts (close to their insertions) and became thinner towards the free ends. The
      horizontal band of the mediopatellar fold was observed in all cases, with an
      accompanying vertical band in 76.7% of the cases. A horizontally located lateral
      fold was absent in both knees of one fetus. The frequency of a horizontally
      located lateral fold was 93.3% and a vertical fold was accompanying in only 28.6%
      of these cases. It is of note that the horizontal band of the mediopatellar fold
      observed in all specimens has never been defined in previous classifications. In
      10% of the knees, the vertically located part of the mediopatellar fold presented
      as a large band extending upward and being squeezed between the articular surface
      of the patella and the medial condyle of the femur. The lateral fold was observed
      as a large band in 10% of the knees. Another observation was that the higher
      level the vertical band of the mediopatellar and lateral folds began, the wider
      the horizontal band was, occupying more place in the patellofemoral space. It was
      remarkable that the frequencies of the vertically located parts of the lateral
      and mediopatellar folds in fetuses were higher than those reported for the adults
      in the literature. CONCLUSION: Our findings suggest that the resorption process
      of the mesenchymal tissue, particularly in the lateral part, continues until
      adulthood and causes age-dependent alterations in the formation of intra
      articular folds. The synovial folds occupy more space between the patella and
      femur in the early stages of life than seen in adults. This may be a more
      frequent cause of unexplained knee pain in children than expected.

PMID- 21088465
TI  - Prospective analysis of surgical outcomes in patients undergoing decompressive
      laminectomy and posterior instrumentation for degenerative lumbar spinal
      stenosis.
AB  - OBJECTIVES: The aim of this study was to evaluate the outcome of wide surgical
      decompression and concomitant posterior instrumentation in patients with
      degenerative lumbar spinal stenosis. METHODS: Thirty-seven consecutive patients
      (14 men, 23 women; mean age 64 years; range 36 to 82 years) with degenerative
      lumbar spinal stenosis were prospectively evaluated following surgical treatment
      with spinal decompression and concomitant instrumented posterior fusion. The mean
      duration of symptoms before surgery was 24 months (range 12 to 60 months).
      Preoperatively, six patients had degenerative spondylolisthesis (grade 1) and two
      patients had degenerative lumbar scoliosis. Decompression was performed at one
      level in four patients, at two levels in 16 patients, at three levels in 11
      patients, and at four levels in six patients. Discectomy was also performed in
      seven patients. Preoperatively and postoperatively, the patients were assessed by
      the Oswestry Disability Index and a visual analog scale for overall pain (leg and
      low back pain). The satisfaction level of the patients for surgical outcome was
      also questioned. The mean follow-up period was 4.6 years (range 1 to 7 years).
      RESULTS: Preoperatively, the mean Oswestry Disability Index score was 60.5% and
      the mean overall pain score was 7.5. Postoperatively, the Oswestry Disability
      Index score significantly decreased to 36.8% and the overall pain score
      significantly decreased to 3.5 (p<0.001). Preoperative and postoperative walking
      distances of the patients were as follows, respectively: more than 1,000 meters
      (6 and 14 patients), 500 to 1,000 meters (5 and 7 patients), less than 500 meters
      (26 and 16 patients). Twenty patients did not use any analgesics and eight
      patients used analgesics on a weekly basis. Twenty-six patients were satisfied
      with the surgical outcome, nine patients were somewhat satisfied, and two
      patients were dissatisfied. Overall, the outcomes were excellent to good in 22
      patients (59.5%). None of the patients required revision surgery. CONCLUSION:
      Most patients with degenerative lumbar spinal stenosis benefit from decompressive
      surgery. Patients with long-standing preoperative symptoms and concomitant
      diseases often have poor results and are less satisfied with the postoperative
      outcome.

PMID- 21088466
TI  - Evaluation of the medial longitudinal arch: a comparison between the dynamic
      plantar pressure measurement system and radiographic analysis.
AB  - OBJECTIVES: The measurement of the medial longitudinal arch (MLA) of the foot is
      a controversial issue in orthopedics. Several methods have been developed to
      define and determine the MLA, but none of them are universally accepted. The
      purpose of this study was to compare some statically obtained radiographic angles
      with the dynamic plantar pressure distribution measurement system for the
      evaluation of the MLA in healthy individuals. METHODS: A total of 95 subjects (72
      females, 23 males; mean age 37.8 years; range 11 to 85 years) were
      retrospectively evaluated. All the subjects were referred to the pedobarography
      laboratory for varying causes, had foot radiographies, and were evaluated as
      having normal feet. On standard lateral weight-bearing radiographs of the foot,
      the lateral talocalcaneal angle, talo-first metatarsal angle, talohorizontal
      angle, and calcaneal pitch angle were measured. The plantar pressure distribution
      was measured by the EMED-SF system. To evaluate the MLA, the arch index method
      was used. The arch index was calculated by the ratio of the pressure area of the
      midfoot to the sum of the forefoot, midfoot, and the hindfoot areas. Correlations
      between the radiographic angles and the arch index were analyzed by the Pearson
      correlation test. RESULTS: The mean values of the lateral talocalcaneal angle,
      talo-first metatarsal angle, talohorizontal angle, and calcaneal pitch angle were
      43.2, 7.2, 29.5, and 41 degrees, respectively. The mean value of the arch index
      was 0.12 (range 0.04 to 0.17). There was no significant correlation between the
      arch index and gender (r=-0.10, p>0.05). The talo-first metatarsal (r=0.38) and
      talohorizontal (r=0.19) angles were found to be in significant correlation with
      the arch index (p<0.05), whereas the talocalcaneal (r=-0.16) and calcaneal pitch
      (r=-0.10) angles did not show correlation with the arch index (p>0.05).
      CONCLUSION: The arch index method is a simple and reproducible pedobarographic
      measurement for the evaluation of the MLA. However, the angles measured on
      statically obtained radiographs and showing correlations with the arch index may
      give similar results concerning the MLA. Both static and dynamic methods can be
      utilized in the evaluation of the MLA.

PMID- 21088467
TI  - Secondary aneurysmal bone cyst of the patella.
AB  - Aneurysmal bone cyst accounts for 1% of primary bone tumors and is one of the
      benign tumor-like lesions. Patellar involvement is quite rare. Its development on
      the basis of any previous lesion such as chondroblastoma is called secondary
      aneurysmal bone cyst. A 26-year-old male patient presented with right knee pain
      of three-year history. Physical examination showed a firm, immobile swelling at
      the anterior aspect of the right knee, without increase in temperature or redness
      of the skin. There was no pain on palpation and joint range of motion was normal.
      Radiological studies were suggestive of an aneurysmal bone cyst. At surgery, the
      cystic lesion was removed via curettage and the residual cavity was filled with
      an autogenous bone graft taken from the iliac wing. The histopathologic diagnosis
      was secondary aneurysmal bone cyst in association with chondroblastoma. During a
      1.5-year follow-up, the patient had no complaint and no recurrence was observed.

PMID- 21088468
TI  - A glomus tumor anterior to the patellar tendon: a case report.
AB  - Glomus tumors are benign neoplasms originating from the glomus body. They are
      most frequently found in the nail bed of the hands, and their occurrence in other
      parts of the body is rare. A 75-year-old man presented with left anterior knee
      pain of 30-year history, that became more intense with light touch or clothing
      and increased in severity despite medical treatment. Physical examination showed
      a painful, soft, mobile, red-purple colored mass, 2 x 2 cm in size, at the
      inferior border of the patella. Plain radiographs showed no pathology other than
      mild degenerative changes. Magnetic resonance imaging revealed a mass lesion, 1.5
      x 1.1 x 2 cm in size, located at the anterior border of the patellar tendon,
      which showed hypointensity on T1A-weighted sequences and hyperintensity on T2
      weighted sequences and T2-weighted sequences with fat saturation. The mass was
      excised and the histopathological diagnosis was reported as glomangioma.
      Postoperatively, the patient had no complaint of pain and no recurrence was
      observed during a two-year follow-up.

PMID- 21088469
TI  - The linea aspera-pilaster complex as a possible cause of confusion with the
      'flame sign': a case report.
AB  - The linea aspera is an important osteological feature onto which many muscles
      insert. Evolutionary as well as individual lifestyle changes can lead to the
      radiographic appearance of the linea aspera-pilaster complex as the track sign.
      This rare feature is known to radiologists and anthropologists as a normal
      roentgen and anatomical variant. However, its knowledge is less common even
      amongst experienced senior orthopedic surgeons. The track sign can be readily
      confused with the pathological 'flame sign' of Paget's disease leading to
      unnecessary investigations. This case report intends to increase awareness
      amongst experienced and trainee orthopedic surgeons alike, of the physiological
      existence of the track sign.

PMID- 21088470
TI  - Microglial P2X7 receptor expression is accompanied by neuronal damage in the
      cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease.
AB  - The possibility that P2X7 receptor (P2X7R) expression in microglia would mediate
      neuronal damage via reactive oxygen species (ROS) production was examined in the
      APPswe/PS1dE9 mouse model of Alzheimer's disease (AD). P2X7R was predominantly
      expressed in CD11b-immunopositive microglia from 3 months of age before Abeta
      plaque formation. In addition, gp91phox, a catalytic subunit of NADPH oxidase,
      and ethidium fluorescence were detected in P2X7R-positive microglial cells of
      animals at 6 months of age, indicating that P2X7R-positive microglia could
      produce ROS. Postsynaptic density 95-positive dendrites showed significant damage
      in regions positive for P2X7R in the cerebral cortex of 6 month-old mice. Taken
      together, up-regulation of P2X7R activation and ROS production in microglia are
      parallel with Abeta increase and correlate with synaptotoxicity in AD.

PMID- 21088471
TI  - Adrenal nodules in patients with Cushing's disease: prevalence, clinical
      significance and follow-up.
AB  - Adrenal glands in Cushing's disease (CD) range from normal to showing diffuse
      enlargement in most cases. The finding of nodular lesions has been reported, but
      information about prevalence and evolution is described in few reports. AIM: To
      investigate the prevalence of nodular adrenal glands in patients with CD and
      assess its evolution after disease remission. SUBJECTS AND METHODS: We assessed
      41 CD patients' abdominal computed tomography (CT) scans obtained during the
      active phase of the disease and evaluated the dynamics of ACTH and cortisol
      secretion. CT was repeated after disease remission in patients with adrenal
      nodules. RESULTS: Fifteen of 41 patients had nodular and the remaining 26 had
      normal or enlarged adrenal glands. Patients with nodules were older (45.1 +/- 8.8
      vs 36.9 +/- 12.7 yr; p=0.03) and had longer-standing disease (57.3 +/- 56.9 vs
      32.9 +/- 29.1 months; p=0.05) than patients with normal/enlarged adrenal glands.
      ACTH (45.4 +/- 21.3 vs 70.5 +/- 39.1 pg/ml; p=0.04) and urinary free cortisol
      levels (606.1 +/- 512.3 vs 301.0 +/- 224.7 MUg/day, p=0.01) were significantly
      lower in patients with adrenal nodules while there were no differences between
      the groups in terms of dynamic tests results. Post-operative follow-up showed
      regression or shrinkage of the nodules in 8 out of 10 patients in disease
      remission. CONCLUSIONS: We found that adrenal nodular glands are a frequent
      finding in CD in particular in older patients and in those with a longerstanding
      disease. Nevertheless, a high percentage of nodules regression or shrinking was
      evidenced in our series after disease remission.

PMID- 21088472
TI  - Serum uric acid in relation with the metabolic syndrome components and
      adiponectin levels in Lebanese University students.
AB  - BACKGROUND: The relation between serum uric acid (SUA) and metabolic syndrome
      (MetS) parameters has never been studied in a young Middle-Eastern population. In
      addition, the relation between SUA and adiponectin was poorly studied. METHODS:
      We looked at the relation between SUA, and both adiponectin and MetS components
      in 381 randomly selected Lebanese university students (201 males and 180
      females). RESULTS: SUA was positively correlated with body mass index (BMI),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), waist
      circumference (WC), fasting blood glucose (FPG), triglycerides, total and LDL
      cholesterol, and homeostasis model assessment (HOMA) index (p<0.001 for all
      variables, p<0.01 for FPG) and inversely correlated with HDL-cholesterol and
      adiponectin (p<0.001 for both variables). In men, SUA was positively correlated
      with BMI, WC, SBP, DBP, FPG, triglycerides, total and LDL-cholesterol, and HOMA
      index and inversely correlated with adiponectin (p<0.001 for all variables,
      p<0.05 for adiponectin); these correlations persisted after BMI adjustment, for
      WC, FPG, triglycerides, total-cholesterol, LDL-cholesterol, and HOMA index. In
      women, SUA was positively correlated with total and LDL-cholesterol (p<0.001),
      independently of BMI. In a multiple regression analysis, SUA was independently
      associated with WC, triglycerides, total cholesterol, HDLcholesterol and
      adiponectin in the overall population while, in men, it was associated with
      triglycerides, total-cholesterol, and WC. CONCLUSION: Our results suggest, in
      young adults, a gender difference in the relation between SUA and both
      adiponectin and MetS parameters. In addition, we observed in both genders a
      strong relation of SUA with total cholesterol. Further studies are needed in
      larger populations in order to elucidate these findings.

PMID- 21088473
TI  - Thyroid hormone, amiodarone therapy, and prognosis in left ventricular systolic
      dysfunction.
AB  - BACKGROUND: Amiodarone protects patients with left ventricular systolic
      dysfunction (LVSD) against serious arrhythmias, but it also has numerous side
      effects on non-cardiac organs, such as the thyroid. Indeed, amiodarone may
      inhibit the peripheral conversion of T4 into T3. Pathologically reduced serum
      levels of T3 - the so-called "low T3 syndrome" (LOWT3) - increase mortality in
      patients with LVSD and not on amiodarone. AIM: The aim of the study was to
      examine the relationship between thyroid hormone status, amiodarone therapy, and
      outcome in a population with LVSD. MATERIAL/ SUBJECTS AND METHODS: A total of
      2344 patients with LVSD and free of overt hyper- and hypothyroidism were
      enrolled. The population was divided into 4 groups: group 1 (LOWT3 and amiodarone
      therapy, no.=126), group 2 (isolated amiodarone therapy, no.=74), group 3
      (isolated LOWT3, no.=682), group 4 (controls, no.=1462). RESULTS: Kaplan-Meier
      curves showed, after a mean follow-up of 31 months, increased total and cardiac
      mortality in groups 1 (30% and 20%, respectively), 2 (23%, 11%), and 3 (22%, 12%)
      compared to group 4 (total mortality log-rank 82.8, p<0.0001; cardiac mortality
      log-rank 63.1, p<0.0001). At Cox analysis, adjusted for several clinical
      variables, survival was reduced in groups 1 and 3 compared to group 4. Group 2
      had a similar mortality to group 4, although the number of patients was too
      limited to accurately assess the effect of amiodarone on long-term prognosis.
      CONCLUSIONS: LOWT3 exerts an adverse impact on prognosis in LVSD, which is not
      influenced by concomitant amiodarone therapy.

PMID- 21088476
TI  - Follow the leader: LIM kinases pave the way for collective tumor cell invasion.

PMID- 21088474
TI  - Oxidative stress markers are not valuable markers in lean and early age of
      polycystic ovary syndrome patients.
AB  - BACKGROUND: Early atherosclerosis and increased risk of cardiovascular diseases
      (CVD) have been reported in patients with polycystic ovary syndrome (PCOS).
      Oxidative stress is an accepted risk factor for the development of CVD. AIM: To
      evaluate the association between oxidative stress markers [ischemia-modified
      albumin (IMA), total antioxidant status (TAS), and total oxidant status (TOS)
      levels], carotid intima- media thickness (CIMT), endocrine and metabolic
      parameters in patients with PCOS. MATERIALS, SUBJECTS, AND METHODS: We studied 52
      patients with PCOS and 36 age- and body mass index (BMI)-matched controls. The
      diagnosis of PCOS was made according to the Rotterdam criteria. Metabolic,
      hormonal parameter and IMA, TAS, TOS levels were measured. RESULTS: No
      statistically significant difference was determined in relation to age, BMI and
      waist-hip ratio, IMA, TAS, and TOS levels between groups. Mean IMA level was
      higher in PCOS patients, however, statistical significant difference was not
      observed. Mean CIMT and homeostasis model assessment of insulin resistance levels
      were significantly higher in patients with PCOS than in control subjects.
      CONCLUSION: Our study has shown that although CIMT levels, showing CVD risk, were
      higher in PCOS patients, TAS and TOS oxidative stress markers were found to be
      similar between groups, IMA was higher in PCOS patients however the difference
      was not reach statistical significant. The present results suggest that CIMT
      increases before the state of ischemia and shows preischemic state of
      vasculature, while oxidative stress markers are considered to be indicators of
      ischemia and reperfusion injury in progressive vascular disease. Further studies
      are needed to show the association between oxidative stress markers, CVD and
      PCOS.

PMID- 21088477
TI  - Genome-wide RNAi screen discovers functional coupling of alternative splicing and
      cell cycle control to apoptosis regulation.

PMID- 21088475
TI  - Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease:
      an important but poorly studied relationship.
AB  - Vitamin K denotes a group of lipophilic vitamins determining post-translational
      modification of proteins. There are 2 main forms of vitamin K: vitamin K1
      (phylloquinone, found in vegetables); vitamin K2 (menaquinone, produced by
      bacteria in the intestine and in fermented foods). Vitamin K stores are limited
      in humans, but it can be recycled. Vitamin K1 is principally transported to the
      liver, regulating the production of coagulation factors. Vitamin K2, instead, is
      also transported to extra-hepatic tissues, such as bone and arteries, regulating
      the activity of matrix Gla-protein (MGP) and osteocalcin [bone Gla-protein
      (BGP)]. In patients with chronic kidney disease (CKD), cardiovascular mortality
      is the first cause of death. Some pathogenetic mechanisms of vascular
      calcification (such as hyperparathyroidism, hyperphosphatemia, hypercalcemia,
      role of vitamin D) have been widely investigated, but the potential role of
      vitamin K is still uncertain. Vitamin K could play a key role, as it transforms
      glutamic acid residues into gamma-carboxyglutamic acid, through a carboxylation
      process, makings both MGP (cMGP) and BGP (cBGP) biologically active. cMGP
      inhibits vascular calcifications (VC), while cBGP has an important role for a
      proper mineralization process. Uncarboxylated MGP and BGP (ucMGP and ucBGP)
      concentrations are indirect markers of vitamin K2 deficiency. The purpose of this
      review is to analyze the current literature to understand the relationship
      between vitamin K2 status, fragility fractures and VC in CKD patients. This
      analysis could be of help in planning investigations of Vitamin K status and its
      possible supplementation in CKD patients to avert fragility fractures and VC.

PMID- 21088478
TI  - The importance of being DNA.

PMID- 21088479
TI  - The mitochondrial apoptosis pathway and p66Shc--a regulatory redox enzyme or an
      adapter protein snuggling around?

PMID- 21088480
TI  - Hedgehog signalling in T-cell development: a non-redundant role for Gli1.

PMID- 21088481
TI  - Dissecting the functions of Gli transcription factors in T-cell development.

PMID- 21088482
TI  - Small RFC subunits make a big difference.

PMID- 21088483
TI  - MicroRNAs are invading the tumor microenvironment: Fibroblast microRNAs regulate
      tumor cell motility and invasiveness.

PMID- 21088484
TI  - Finding markers for cancer stem cells in renal cell carcinoma: looking beyond
      CD133.

PMID- 21088486
TI  - Metformin against TGFbeta-induced epithelial-to-mesenchymal transition (EMT):
      from cancer stem cells to aging-associated fibrosis.
AB  - Transforming Growth Factor-b (TGFb) is a major driving force of the Epithelial-to
      Mesenchymal (EMT) genetic program, which becomes overactive in the
      pathophysiology of many age-related human diseases.  TGFb-driven EMT is
      sufficient to generate migrating cancer stem cells by directly linking the
      acquisition of cellular motility with the maintenance of tumor-initiating
      (stemness) capacity.  Chronic diseases exhibiting excessive fibrosis can be
      caused by repeated and sustained infliction of TGFb-driven EMT, which increases
      collagen and extracellular matrix synthesis.  Pharmacological prevention and/or
      reversal of TGFb-induced EMT may therefore have important clinical applications
      in the management of cancer metastasis as well as in the prevention and/or
      treatment of end-state organ failures.  Earlier studies from our group have
      revealed that clinically-relevant concentrations of the biguanide derivative
      metformin, the most widely used oral agent to lower blood glucose concentration
      in patients with type 2 diabetes and metabolic syndrome, notably decreased both
      the self-renewal and the proliferation of trastuzumab-refractory breast cancer
      stem cell populations.  Given that: a.) tumor-initiating cancer stem cells
      display a significant enrichment in the expression of basal/mesenchymal or
      myoepithelial markers, including an increased secretion of TGFb; b.) metformin
      treatment impedes the ontogeny of generating the stem cell phenotype by
      transcriptionally repressing key drivers of the EMT genetic program (e.g. ZEB1,
      TWIST1, SNAIL2 [Slug], TGFbs), we recently hypothesized that prevention of TGFb
      induced EMT might represent a common molecular mechanism underlying the anti
      cancer stem cells and anti-fibrotic actions of metformin.  Remarkably, metformin
      exposure not only impedes TGFb-promoted loss of the epithelial marker E-cadherin
      in MCF-7 breast cancer cells but it prevents further TGF-induced cell scattering
      and accumulation of the mesenchymal marker vimentin in Madin-Darby canine kidney
      (MDCK) cells.  We now propose that metformin, by weakening the ability of TGFb
      signaling to fully induce mesenchymal cell states in a variety of pathological
      processes including fibrosis (e.g. chronic renal disease, non-alcoholic
      steatohepatitis, heart failure or sclerosis) and malignant progression (and
      likely by reducing TGFb-regulated inflammation and immune responses -inflamm
      aging-), molecularly behaves as a bona fide anti-aging modality.

PMID- 21088485
TI  - Dicer-independent, Ago2-mediated microRNA biogenesis in vertebrates.
AB  - A canonical biogenesis pathway involving sequential cleavage by the Drosha and
      Dicer RNAse III enzymes governs the maturation of most animal microRNAs. However,
      there exist a variety of alternative miRNA biogenesis pathways, most of which
      bypass Drosha processing. Recently, three groups described for the first time a
      vertebrate microRNA pathway that bypasses Dicer cleavage. This mechanism was
      characterized with respect to the highly conserved vertebrate gene mir-451, for
      which Drosha processing yields a short (42 nucleotide) hairpin that is directly
      loaded into Ago2, the sole vertebrate "Slicer" Argonaute. Ago2-mediated cleavage
      of this hairpin yields a 30 nucleotide intermediate, whose 3' end is resected to
      generate the dominantly cloned ~23 nucleotide mature miR-451. Knowledge of this
      pathway provides an unprecedented tool with which to express microRNAs and small
      interfering RNAs in Dicer mutant cells. More generally, the mir-451 backbone
      constitutes a new platform for gene silencing that complements existing shRNA
      technology.

PMID- 21088487
TI  - Fasting and differential chemotherapy protection in patients.
AB  - Chronic calorie restriction has been known for decades to prevent or retard
      cancer growth, but its weight-loss effect and the potential problems associated
      with combining it with chemotherapy have prevented its clinical application.
      Based on the discovery in model organisms that short term starvation (STS or
      fasting) causes a rapid switch of cells to a protected mode, we described a
      fasting-based intervention that causes remarkable changes in the levels of
      glucose, IGF-I and many other proteins and molecules and is capable of protecting
      mammalian cells and mice from various toxins, including chemotherapy. Because
      oncogenes prevent the cellular switch to this stress resistance mode, starvation
      for 48 hours or longer protects normal yeast and mammalian cells and mice but not
      cancer cells from chemotherapy, an effect we termed Differential Stress
      Resistance (DSR). In a recent article, 10 patients who fasted in combination with
      chemotherapy, reported that fasting was not only feasible and safe but caused a
      reduction in a wide range of side effects accompanied by an apparently normal and
      possibly augmented chemotherapy efficacy. Together with the remarkable results
      observed in animals, these data provide preliminary evidence in support of the
      human application of this fundamental biogerontology finding, particularly for
      terminal patients receiving chemotherapy. Here we briefly discuss the basic, pre
      clinical, and clinical studies on fasting and cancer therapy.

PMID- 21088489
TI  - Same partners, different dance: involvement of DNA replication proteins in
      centrosome regulation.
AB  - Genome replication is the most fundamental element of the continuity of life. In
      eukaryotes, DNA replication is regulated by an elegant network of many different
      protein factors to ensure the timely and accurate copying of their entire genome
      once per cell cycle. The replication factors include the maintenance (MCM)
      proteins, Cdt1, Cdc6, Cdc7, Cdc45, and geminin. All of these proteins are
      involved in the regulation of DNA replication at the initiation step.
      Interestingly, recent studies have shown that some of these replication proteins
      also localize to the centrosome, often throughout the entire cell cycle. These
      centrosomally localized replication proteins appear to play essential roles in
      the regulation of centrosome biogenesis, suggesting that genome replication and
      segregation are regulated interdependently. In this review, we summarize and
      discuss the inter-dependent regulation played by some of the replication
      proteins.

PMID- 21088490
TI  - Activation of Cdk2/Cyclin E complexes is dependent on the origin of replication
      licensing factor Cdc6 in mammalian cells.
AB  - Cyclin E-associated CDK2 activity is required for the initiation of DNA synthesis
      in human cells. CDK2 activity is tightly regulated; CDK2 must be in the nucleus,
      bound to a cyclin, phosphorylated on T160, and dephosphorylated on T14/Y15 for
      complete kinase activation. Nuclear localization exposes CDK2 to activating
      enzymes (CAK, Cdc25A) in stimulated cells. Previous studies from our lab indicate
      CDK2 nuclear localization and cyclin E co-expression are insufficient to cause
      CDK2 activation or T160 phosphorylation in stimulated IIC9 cells; these
      activities still require serum stimulation and ERK kinase activity. Recent
      studies have implicated a role for origin of replication (ORC) licensing proteins
      in the activation of G1/S Cdks. In this study, we show that CDK2 associates with
      chromatin and Cdc6 in an ERK-dependent manner following stimulation of IIC9 CHEF
      cells. We show that nuclear-localized CDK2 (CDK2-NLS) ectopically expressed with
      cyclin E requires mitogenic stimulation and ERK activation for chromatin
      association, in addition to previously shown kinase activation and T160
      phosphorylation in IIC9 cells. Additionally, we show that expression of Cdc6 in
      stimulated IIC9 cells treated with ERK inhibitor rescues CDK2-NLS chromatin
      association, kinase activation, and T160 phosphorylation. From the above data, we
      deduce ERK-dependent CDK2 activation is due in part to ERK-dependent Cdc6
      expression. To examine the role of Cdc6 directly in stimulated primary human
      fibroblasts, we used RNA interference to attenuate the expression of Cdc6. We
      show that Cdc6 expression is required for CDK2 chromatin association and kinase
      activation in stimulated primary human fibroblasts. Additionally, we show that
      Cdc6 expression is required for the initiation of DNA synthesis and S phase entry
      in stimulated primary human fibroblasts. Ultimately, this data implicates Cdc6
      expression as an important mitogen-induced mechanism in the activation of
      CDK2/cyclin E, the initiation of DNA synthesis, and the regulation of G1-S phase
      progression.

PMID- 21088488
TI  - REST and CoREST are transcriptional and epigenetic regulators of seminal neural
      fate decisions.
AB  - Complementary transcriptional and epigenetic regulatory factors (e.g., histone
      and chromatin modifying enzymes and non-coding RNAs) regulate genes responsible
      for mediating neural stem cell maintenance and lineage restriction, neuronal and
      glial lineage specification, and progressive stages of lineage maturation.
      However, an overall understanding of the mechanisms that sense and integrate
      developmental signals at the genomic level and control cell type-specific gene
      network deployment has not emerged. REST and CoREST are central players in the
      transcriptional and epigenetic regulatory circuitry that is responsible for
      modulating neural genes, and they have been implicated in establishing cell
      identity and function, both within the nervous system and beyond it. Herein, we
      discuss the emerging context-specific roles of REST and CoREST and highlight our
      recent studies aimed at elucidating their neural developmental cell type- and
      stage-specific actions. These observations support the conclusion that REST and
      CoREST act as master regulators of key neural cell fate decisions.

PMID- 21088491
TI  - Stapled peptides in the p53 pathway: computer simulations reveal novel
      interactions of the staples with the target protein.
AB  - Atomistic simulations of a set of stapled peptides derived from the
      transactivation domain of p53 (designed by Verdine & colleagues, JACS 2007
      129:2456) and complexed to MDM2 reveal that the good binders are uniquely
      characterized by higher helicity and by extensive interactions between the
      hydrocarbon staples and the MDM2 surface; in contrast the poor binders have
      reduced helicity and their staples are mostly solvent exposed. Our studies also
      find that the best binders can also potentially inhibit MDMX with similar
      affinities, suggesting that such stapled peptides can be evolved for dual
      inhibition with therapeutic potential.

PMID- 21088493
TI  - MicroRNA-449a levels increase by several orders of magnitude during mucociliary
      differentiation of airway epithelia.
AB  - MicroRNAs of the miR-34/449 family mediate cell cycle arrest and tumor
      suppression.  Here we show that the expression of microRNA miR-449a, unlike its
      paralogue miR-34a, is highly tissue specific and largely restricted to pulmonary
      and testicular tissue. MiR-449a levels in the murine lung are particularly high
      shortly before and after birth, coinciding with terminal differentiation of lung
      epithelia. Strikingly, miR-449a is upregulated by more than 1000-fold when
      epithelial cells from human airways are lifted from a liquid environment to air,
      allowing them to undergo mucociliary differentiation. The induction of miR-449a
      occurs in parallel to its host gene CDC20B and the transcription factor FoxJ1.
      Exposure to tobacco smoke induces a moderate further increase in the levels of
      miR-449a, and also miR-34a, in differentiated airway epithelia. We propose that
      miR-449a can serve as an exquisitely sensitive and specific biomarker for the
      differentiation of bronchial epithelia. Moreover, miR-449a may actively promote
      mucociliary differentiation through its ability to block cell cycle progression,
      and it may conribute to a first line of defence against genotoxic stress by its
      proapoptotic functions.

PMID- 21088492
TI  - Transcriptional regulation of HIV-1 gene expression by p53.
AB  - Several reports have pointed to the negative involvement of p53 in
      transcriptional regulation of the human immunodeficiency virus type 1 long
      terminal repeat (HIV-1 LTR). However, the mechanisms of this negative effect
      remain unclear. In here, we showed that over expression of p53 wild type
      prevented the phosphorylation of serine 2 in the carboxyl terminal domain (CTD)
      of RNA polymerase II. As a result of this inhibition, p53 stalled transcriptional
      elongation on the HIV-1 LTR leading to a significant reduction of HIV-1
      replication in primary microglia and astrocytes. However, despite the delay/pause
      caused by p53, viral transcription and replication decreased and then salvaged.
      These studies suggest that the negative effect of p53 is alleviated by a third
      factor. In this regard, our Preliminary Data point to the involvement of the
      Pirh2 protein in p53 inhibition. Therefore, we suggest that p53 may be a novel
      therapeutic target for the inhibition of HIV-1 gene expression and replication
      and the treatment of AIDS.

PMID- 21088495
TI  - Histone modifications regulate the norepinephrine transporter gene.

PMID- 21088494
TI  - Interaction of regulators Mdm2 and Mdmx with transcription factors p53, p63 and
      p73.
AB  - The negative regulation of p53, a major human tumor suppressor, by Mdm2 and Mdmx
      is crucial for the survival of a cell, whereas its aberrant function is a common
      feature of cancer.  Both Mdm proteins act through the spatial occlusion of the
      p53 transactivation (TA) domain and by the ubiquitination of p53, resulting in
      its degradation.  Two p53 homologues, p63 and p73, have been described in humans.
      Unlike p53, these proteins regulate developmental processes rather than genome
      stability.  Both p63 and p73 contain TA domains homologous to that of p53, but
      relatively little is known about their regulation by Mdm2 or Mdmx.  Here, we
      present a detailed characterization of the interaction of Mdm2 and Mdmx with the
      TA domains of p63 and p73. Earlier reports of Mdm2 and Mdmx interactions with p73
      are substantiated by the detailed quantitative characterization reported in this
      study. Most importantly, earlier contradictions concerning the presumed
      interaction of the Mdm proteins with p63 are convincingly resolved and for the
      first time, the affinities of these interactions are determined.  Finally, the
      contribution of these findings to our understanding of the physiological role of
      these interactions is discussed.

PMID- 21088496
TI  - FIP200, an essential component of mammalian autophagy is indispensible for fetal
      hematopoiesis.
AB  - Autophagy, an evolutionarily conserved cellular process for bulk protein
      degradation through lysosomes, plays important roles in various physiological and
      pathological processes. Recent studies suggest that autophagy also participates
      in erythroid development. However, to what extent autophagy is involved in
      hematopoiesis is largely unknown. FIP200 (focal adhesion kinase family
      interacting protein of 200 kD) is a newly identified essential autophagy gene and
      a component of the ULK-Atg13-FIP200 complex. We show that mice lacking FIP200 in
      hematopoietic cells (CKO mice) experience perinatal lethality associated with
      severe erythroblastic anemia. FIP200 is cell-autonomously required for the
      maintenance and function of fetal hematopoietic stem cells (HSCs). FIP200
      deletion in HSCs does not result in increased apoptosis. However, aberrantly
      increased HSC proliferation and myeloid expansion are found in CKO embryos, which
      may be responsible for the depletion of fetal HSCs. Consistent with an essential
      role of FIP200 in autophagy, FIP200-null fetal HSCs as well as other
      hematopoietic cells exhibit increased mitochondria mass and reactive oxygen
      species (ROS). Together, our data identify FIP200 as a key intrinsic regulator of
      fetal HSCs and suggest a role of autophagy in fetal hematopoiesis and the
      maintenance of fetal HSCs.

PMID- 21088497
TI  - Prostate cancer genomic signature offers prognostic value.
AB  - Previous attempts to link prostate cancer progression to genetic alterations have
      been unsuccessful, and consequently, there is still no reliable predictor of
      prognosis for men with this disease. A recent study by Taylor et al., published
      in Cancer Cell, assesses copy number alterations, mutations, and transcriptomes
      in 218 tumors and 12 prostate cancer cell lines and xenografts. Their analysis
      identifies frequencies of ERG alterations, 8p loss and 8q gain similar to
      previous findings. It also reveals novel genetic factors in prostate cancer
      progression, including the androgen receptor coactivator, NCOA2, which serves as
      an oncogene in about 11% of tumors, and a deletion at chromosome 3p14, which was
      associated with TMPRSS-ERG fusion. The copy number alteration data demonstrates
      six distinct subgroups of prostate cancer with considerable variation in time to
      biochemical relapse. Classification of prostate cancer into these genetic
      subgroups may help clinicians predict the likelihood of disease progression in
      newly diagnosed men, ultimately guiding treatment decisions and therapy
      development.

PMID- 21088498
TI  - Regulation of DeltaNp63alpha by NFkappaBeta.
AB  - DeltaNp63alpha, the dominant negative isoform of the p63 family is an essential
      survival factor in head and neck squamous cell carcinoma. This isoform has been
      shown to be down regulated in response to several DNA damaging agents, thereby
      enabling an effective cellular response to genotoxic agents. Here, we identify a
      key molecular mechanism underlying the regulation of DeltaNp63alpha expression in
      response to extrinsic stimuli, such as chemotherapeutic agents. We show that
      DeltaNp63alpha interacts with NF-kappaBeta in presence of cisplatin. We find that
      NF-kappaBeta promotes ubiquitin-mediated proteasomal degradation of
      DeltaNp63alpha. Chemotherapy-induced stimulation of NF-kappaBeta leads to
      degradation of DeltaNp63alpha and augments trans-activation of p53 family-induced
      genes involved in the cellular response to DNA damage. Conversely, inhibition of
      NF-kappaBeta with siRNA-mediated silencing NF-kappaBeta expression attenuates
      chemotherapy induced degradation of DeltaNp63alpha . These data demonstrate that
      NF-kappaBeta plays an essential role in regulating DeltaNp63alpha in response to
      extrinsic stimuli. Our findings suggest that the activation of NF-kappaBeta may
      be a mechanism by which levels of DeltaNp63alpha are reduced, thereby rendering
      the cells susceptible to cell death in the face of cellular stress or DNA damage.

PMID- 21088499
TI  - Fos-related antigen 1 (Fra-1) pairing with and transactivation of JunB in GBM
      cells.
AB  - Fos-related antigen 1 (Fra-1) plays an important role in maintenance/progression
      of various cancers, including glioblastoma multiforme (GBM). In this study, we
      used both shRNA and siRNA to examine the effect of fra-1 knockdown in GBM cells
      over-expressing Fra-1. Furthermore, we analyzed both the expression of JunB and
      its knockdown, a previously identified target for Fra-1, and also examined its
      potential association with Fra-1. When using fra-1 shRNA and siRNA, we found that
      GBM cells has Fra-1 levels diminished together with the levels of JunB, but Fra-1
      remains unchanged in cells with junB knockdown. This is accompanied by dramatic
      changes in cell morphology and significant alteration in their migration. We next
      uncovered that the expression of JunB increased in response to ectopic Fra-1 and
      also to EGF-induced signaling, similarly to Fra-1. This was associated with an
      avid pairing between phosphorylated Fra-1 and JunB. Importantly, we found that
      Fra-1 paired with JunB binds to an AP-1 site in the junB gene promoter. JunB
      knockdown did not affect Fra-1 and the changes in cell morphology did not fully
      replicate that seen with Fra-1 knockdown. Thus, Fra-1 takes part in a control of
      architecture and migratory nature of GBM cells. Moreover, Fra-1 is a
      phosphorylated factor that transactivates JunB with which it makes effectively AP
      1 pairs in GBM cells.

PMID- 21088500
TI  - Chemo-resistant melanoma sensitized by tamoxifen to low dose curcumin treatment
      through induction of apoptosis and autophagy.
AB  - Melanoma is the deadliest form of skin cancer, which is notoriously aggressive
      and chemo-resistant, and for which there is little effective treatment available
      if it goes undetected. Curcumin from the turmeric spice (Curcuma longa) has long
      been used in Southeast Asian medicine to alleviate ailments and cure an array of
      diseases and disorders. It possesses anti-inflammatory, anti-oxidant and most
      importantly anti-carcinogenic activity. There have been contradictory reports
      discussing the efficacy of curcumin-induced death on melanoma. In this report we
      show that curcumin does induce apoptosis in A375 and the relatively resistant
      G361 malignant human melanoma cell lines at higher doses. Tamoxifen is an
      estrogen receptor (ER) blocker that is used for ER positive breast cancer
      treatment. Recently, tamoxifen has been shown to directly target the
      mitochondria. Given that curcumin is a pro oxidant and tamoxifen can act on
      mitochondria, we ask whether the combinatorial treatment could result in
      synergistic induction of apoptosis in chemo-resistant melanoma. Our results show
      a corresponding increase in phosphatidyl serine flipping, mitochondria
      depolarization and reactive oxygen species (ROS) generation by the combined
      treatment at lower doses. Interestingly, there was significant induction of
      autophagy along with apoptosis following the combined treatment. Importantly, non
      cancerous cells are unaffected by the combination of these non-toxic compounds.
      However, once exposed to low doses of this co-treatment, melanoma cells still
      retain signals to commit suicide even after removal of the drugs. This
      combination provides a non-toxic option for combinatorial chemotherapy with great
      potential for future use.

PMID- 21088501
TI  - Cotransplantation of human umbilical cord blood-derived stromal cells enhances
      hematopoietic reconstitution and engraftment in irradiated BABL/c mice.
AB  - Our previous study demonstrated that human umbilical cord blood-derived stromal
      cells (hUCBDSCs) support the growth of hematopoietic stem cells, and promote the
      expansion of colony-forming units of megakaryocyte (CFU-Mk) even more efficiently
      than human bone marrow stromal cells (hBMSCs). Given the unique role of hUCBDSCs
      in megakaryocytopoiesis in vitro, in this follow up study, we further
      investigated their effects in vivo on hematopoiesis in the setting of
      hematopoietic stem cell (HSC) transplants. After infusing hematopoietic cells
      alone or together with either hUCBDSCs or hBMSCs into lethally irradiated BABL/c
      mice, we examined the engraftment of human CD45+ cells in the mouse bone marrow
      with flow cytometry, observed the survival rate of irradiated mice, obtained
      blood counts and bone marrow biopsies at different time points post-transplant,
      and assessed colony forming and the homing efficiency of hematopoietic cells. By
      comparing HSC transplantation with or without stromal cells, we show here that
      hUCBDSCs efficiently promote the homing of hematopoietic cells to the marrow and
      enhance the engraftment after cotransplantation. They also promote hematopoietic
      reconstitution, particularly of the megakaryocytic lineage, and restore the
      impaired stromal microenvironment after radiation-induced damages. These effects
      of hUCBDSCs are more potent than those of hBMSCs. In conclusion, our findings
      suggest the role of hUCBDSCs to facilitate hematopoietic reconstitution and
      engraftment when cotransplanted with hematopoietic cells.

PMID- 21088502
TI  - The centrosome and mitotic spindle apparatus in cancer and senescence.
AB  - Altered cell division is associated with overproliferation and tumorigenesis,
      however, mitotic aberrations can also trigger antiproliferative responses leading
      to postmitotic cell cycle exit. Here, we focus on the role of the centrosome and
      in particular of centrosomal TACC (transforming acidic coiled coil) proteins in
      tumorigenesis and cellular senescence. We have complied recent evidence that
      inhibition or depletion of various mitotic proteins which take over key in
      centrosome and kinetochore integrity and mitotic checkpoint function in
      sufficient to activate a p53-p21(WAF) driven premature senescence phenotype.
      These findings have direct implications for proliferative tissue homeostasis as
      well as for cellular and organismal aging.

PMID- 21088504
TI  - Increased serum thyroglobulin levels and negative imaging in thyroid cancer
      patients: are there sources of benign secretion? A speculative short review.
AB  - After thyroidectomy and 131I ablation for differentiated thyroid cancer (DTC),
      serum thyroglobulin (Tg) became a sensitive marker of residual disease. It is not
      uncommon to find patients at follow-up with persistent serum Tg levels and no
      other clinical or imaging evidence for the disease. The vast majority of these
      patients, most probably, have occult foci of disease, often in minute cervical
      lymph nodes. A review of the literature including papers published on
      PubMed/Medline until June 2010 was made. In this study we speculated that a
      minority of patients who had undergone surgery for differentiated thyroid cancer
      might have benign sources of Tg secretion at follow-up. These sources may be foci
      of radio-resistant ectopic thyroid tissue or a thyroid stimulating hormone
      stimulated thymus.

PMID- 21088506
TI  - Cannabinoids after cardiac arrest: should your brain be on drugs?

PMID- 21088503
TI  - Anticancer activity of Celastrol in combination with ErbB2-targeted therapeutics
      for treatment of ErbB2-overexpressing breast cancers.
AB  - The receptor tyrosine kinase ErbB2 is overexpressed in up to a third of breast
      cancers, allowing targeted therapy with ErbB2-directed humanized antibodies such
      as Trastuzumab. Concurrent targeting of ErbB2 stability with HSP90 inhibitors is
      synergistic with Trastuzumab, suggesting that pharmacological agents that can
      inhibit HSP90 as well as signaling pathways activated by ErbB2 could be useful
      against ErbB2-overexpressing breast cancers. The triterpene natural product
      Celastrol inhibits HSP90 and several pathways relevant to ErbB2-dependent
      oncogenesis including the NFkappaB pathway and the proteasome, and has shown
      promising activity in other cancer models. Here, we demonstrate that Celastrol
      exhibits in vitro antitumor activity against a panel of human breast cancer cell
      lines with selectivity towards those overexpressing ErbB2. Celastrol strongly
      synergized with ErbB2-targeted therapeutics Trastuzumab and Lapatinib, producing
      higher cytotoxicity with substantially lower doses of Celastrol. Celastrol
      significantly retarded the rate of growth of ErbB2-overexpressing human breast
      cancer cells in a mouse xenograft model with only minor systemic toxicity.
      Mechanistically, Celastrol not only induced the expected ubiquitinylation and
      degradation of ErbB2 and other HSP90 client proteins, but it also increased the
      levels of reactive oxygen species (ROS). Our studies show that the Michael
      Acceptor functionality in Celastrol is important for its ability to destabilize
      ErbB2 and exert its bioactivity against ErbB2-overexpressing breast cancer cells.
      These studies suggest the potential use of Michael acceptor-containing molecules
      as novel therapeutic modalities against ErbB2-driven breast cancer by targeting
      multiple biological attributes of the driver oncogene.

PMID- 21088507
TI  - Interleukin-1 receptor-associated kinase-1: more evidence.

PMID- 21088508
TI  - Myocardial infarction in critically ill patients: a diagnostic challenge.

PMID- 21088509
TI  - All this confusion is killin' me.

PMID- 21088510
TI  - Adiponectin in critically ill patients: more questions than answers?

PMID- 21088511
TI  - Quantitative measures of the ventricular fibrillation waveform and resuscitation
      outcome.

PMID- 21088512
TI  - Understanding and avoiding ventilator-induced lung injury: lessons from an
      insightful experimental study.

PMID- 21088513
TI  - Do activators of the kappa-opioid receptor hold the potential for anti-arrhythmic
      drug development?

PMID- 21088514
TI  - From mice to men: systematic reviews of animal data could make sepsis trials
      safer and more productive.

PMID- 21088516
TI  - A kidney cannot succeed days after cardiac surgery when on high-dose furosemide.

PMID- 21088517
TI  - High-dose renal replacement therapy for acute kidney injury: Systematic review
      and meta-analysis--addendum.

PMID- 21088518
TI  - Odds ratios are contingent on event rates.

PMID- 21088520
TI  - The timing to initiate extracorporeal membrane oxygenation in pH1N1 acute
      respiratory distress syndrome.

PMID- 21088521
TI  - Better hospital nutrition needed to reduce morbidity and mortality from fungal
      infections.

PMID- 21088524
TI  - Abstracts of the Society of Critical Care Medicine 40th Critical Care Congress.
      San Diego, California, USA. January 15-19, 2011.

PMID- 21088527
TI  - Protein intake and growth in the first 24 months of life.

PMID- 21088528
TI  - Does weight gain in infancy influence the later risk of obesity?

PMID- 21088529
TI  - Vitamin D status in growing children: should we routinely screen for vitamin D
      adequacy?

PMID- 21088530
TI  - Mechanisms of appetite regulation.

PMID- 21088531
TI  - Malnutrition and growth.

PMID- 21088532
TI  - Linear growth in anorexia nervosa.

PMID- 21088533
TI  - Nutrition and catch-up growth.

PMID- 21088534
TI  - Nutrition and growth in inflammatory bowel disease.

PMID- 21088535
TI  - Inflammation and growth.

PMID- 21088536
TI  - Growth-promoting hormone therapy in inflammatory bowel disease.

PMID- 21088537
TI  - Short stature and catch-up growth in celiac disease.

PMID- 21088538
TI  - Catch-up growth after correction of gastrointestinal or endocrine disorders.

PMID- 21088539
TI  - Early nutrient supply and the preterm infant.

PMID- 21088540
TI  - Growth in children with neurological impairments.

PMID- 21088541
TI  - GH/IGF axis and longitudinal growth in children with obesity.

PMID- 21088542
TI  - Effects of diet on growth of children with obesity.

PMID- 21088543
TI  - Obesity and insulin resistance in children.

PMID- 21088544
TI  - WHO growth standards--should they be implemented as national standards?

PMID- 21088545
TI  - Effects of muscular strength, exercise order, and acute whole-body vibration
      exposure on bat swing speed.
AB  - The purposes for this study were to investigate effects of acute whole-body
      vibration (WBV) exposure and exercise order on bat speed and to examine
      relationship between muscular strength and bat speed. All participants were
      recreationally trained men (n = 16; 22 +/- 2 years; 181.4 +/- 7.4 cm; 84.7 +/- 9
      kg), with previous baseball experience and were tested for 1 repetitive maximum
      (1RM) strength in squat and bench press. Subjects then participated in 4
      randomized sessions on separate days, each consisting of 3 sets of 5 bat swings.
      Exercises (upper and lower body dynamic and static movements related to bat
      swing) with or without WBV exposure were performed after sets 1 and 2. Trials
      were as follows: no-exercise Control (CTRL), upper body followed by lower body
      exercises without WBV (Arm-Leg NOVIB), upper body followed by lower body
      exercises with WBV (Arm-Leg VIB), and lower body followed by upper body exercises
      with WBV (Leg-Arm VIB). Bat speed was recorded during each swing and averaged
      across sets. Statistical analyses were performed to assess differences across
      sets and trials. Linear regressions analyzed relationship between strength and
      bat speed. A significant relationship existed between bat speed and lower body
      strength (r = 0.406, p = 0.008) but not for upper body strength. The exercise
      order of Arm-Leg VIB significantly increased bat speed by 2.6% (p = 0.02).
      Performing identical order of exercises without vibration (Arm-Leg NOVIB)
      significantly decreased bat speed by 2% (p = 0.039). It was concluded that adding
      vibration exposure to total-body exercises can provide acute enhancements in bat
      speed. Additionally, leg strength was shown to influence bat speed suggesting
      that increasing leg strength may enhance bat speed.

PMID- 21088546
TI  - The physiological demands of hitting and running in tennis on different surfaces.
AB  - The aim of the study was to examine how the training surface (i.e., clay or
      carpet) affects the characteristics (i.e., ball velocity, running pressure,
      running volume, and physiological responses) of a tennis training session. Ten
      competitive healthy and nationally ranked male tennis players (mean +/- SD: age
      24.2 +/- 1.7 years, weight 81.4 +/- 7.6 kg, height 1.88 +/- 0.05 m, body mass
      index 23.1 +/- 1.8) participated in a maximal treadmill test and a field test
      (e.g., an on-court tennis training session, which consisted of 4 exercises).
      Subjects' oxygen uptake (VO2) and heart rate (HR) were recorded by portable
      analyzers, and the ball velocity was measured using a radar gun during the
      training sessions. We did not find any significant influence of the court surface
      on any of the variables analyzed under the standardized exercise conditions of
      the study, as suggested in previous studies conducted under match-play
      conditions. Moreover, data showed significant differences between maximal
      forehand and backhand stroke velocities, the forehand stroke being significantly
      faster (p = 0.01) and more energy demanding on both playing surfaces (clay: 122.0
      +/- 9.1 vs. 111.1 +/- 7.5; carpet: 120.4 +/- 6.0 vs 111.5 +/- 7.0 km.h).
      Comparing the same stroke on the same court surface, but at different stroke
      velocities, we found significant differences (p < 0.05) in all the physiological
      measurements (e.g., HR, %HRmax; VO2; %VO2), which significantly increased with
      hitting velocity.

PMID- 21088547
TI  - A comparison of the physiological exercise intensity differences between shod and
      barefoot submaximal deep-water running at the same cadence.
AB  - The purpose of this investigation was to identify whether physiological exercise
      intensity differed with the use of aquatic training shoes (ATS) during deep-water
      running (DWR) compared to using a barefoot condition. Eight male intercollegiate
      (National Collegiate Athletic Association Division III [NCAA III]) varsity
      distance runners were videotaped from the right sagittal view while running on a
      treadmill (TR) and while barefoot in deep water at 60-70% of their TR VO2max for
      30 minutes. Based on the stride rate of the barefoot DWR trial, a subsequent 30
      minute session was completed while wearing ATS. Variables of interest were energy
      expenditure, oxygen consumption (VO2), heart rate, respiratory exchange ratio
      (RER), and rating of perceived exertion (RPE). Multivariate omnibus tests
      revealed statistically significant differences for energy expenditure (p <
      0.011), VO2 (p < 0.001), RPE (p < 0.001), and RER (p < 0.002). The post hoc
      pairwise comparisons revealed significant differences between barefoot and shod
      DWR conditions for energy expenditure (p < 0.005) and VO2 (p < 0.002),
      representing a 9 and 7.6% increase in exercise intensity demand while running
      shod vs. barefoot. These comparisons also revealed significantly higher RPE and
      RER values while DWR than those found in TR. Wearing the ATS may be recommended
      as a method of statistically significantly increasing the exercise intensity
      while running in deep water as compared to not wearing a shoe. Shod compared to
      TR yields very small differences, which indicates that the shoes may help better
      match land-based running exercise intensities.

PMID- 21088548
TI  - Reliability, minimal detectable change, and normative values for tests of upper
      extremity function and power.
AB  - The purpose of this study was to examine the test-retest reliability, minimal
      detectable change (MDC), and determine normative values of 3 upper extremity (UE)
      tests of function and power. One hundred eighty participants, men (n = 69) and
      women (n = 111), were tested on 3 UE strength and power maneuvers in a
      multicenter study to determine baseline normative values. Forty-six subjects
      returned for a second day of testing within 5 days of the initial assessment for
      the reliability component of the investigation. Explosive power was assessed via
      a seated shot-put test for the dominant and nondominant arms. Relationships
      between the dominant and nondominant arms were also analyzed. A push-up and
      modified pull-up were performed to measure the amount of work performed in short
      (15-second) bursts of activity. The relationship between the push-up and modified
      pull-up was also determined. Analysis showed test-retest reliability for the
      modified pull-up, timed push-up, dominant single-arm seated shot-put tests, and
      nondominant single-arm seated shot-put tests to be intraclass correlation
      coefficient(3,1) 0.958, 0.989, 0.988, and 0.971, respectively. The MDC for both
      the push-up and modified pull-up was 2 repetitions. The MDCs for the shot put
      with the dominant arm and the nondominant arm were 17 and 18 in., respectively.
      The result of this study indicates that these field tests possess excellent
      reliability. Normative values have been identified, which require further
      validation. These tests demonstrate a practical and effective method to measure
      upper extremity functional power.

PMID- 21088549
TI  - Does whole-body vibration training have acute residual effects on postural
      control ability of elderly women?
AB  - The purpose of this study was to investigate acute residual effects of a single
      vibration session on balance control in a group of elderly women. Several
      studies, in fact, have shown that whole-body vibration (WBV) training may improve
      balance in the elderly, but possible side effects of acute exposure to WBV, such
      as temporary reduction of balance control ability because of perturbations of the
      vestibular system, have not been investigated. Twenty-two healthy elderly women
      (71.8 +/- 4.7 years of age) were trained with a 9.5-minute bout of static and
      dynamic knee-extensor exercises executed on a vibrating platform (Well-net Vibe
      Revolution). The vibration frequency was set at 35 Hz. A subgroup of 14 subjects
      performed the same exercise protocol also without the vibrations to discriminate
      between vibration and exercise effects. Balance control ability was assessed
      through computerized posturography: a force plate (Bertec Co, Columbus, OH, USA)
      was used to measure the center of pressure trajectories during 4 different
      experimental trials: before, immediately after, 15 minutes after, and 60 minutes
      after the training. A set of postural parameters, typically adopted to assess
      elderly subjects, was then computed and 2-way analysis of variance was used to
      determine differences between values found in the 4 postural tests (level of
      significance p = 0.05) in the 2 groups. The results showed no significant
      variations in the postural parameters recorded during the 4 sessions. A
      significant group effect was found for 2 postural parameters, with no interaction
      between the 2 factors. In conclusion, the proposed single bout of WBV does not
      induce dangerous acute effects on elderly women balance control ability and could
      be safely administered as part of a long-term intervention program.

PMID- 21088550
TI  - Effects of dynamic warm-up with and without a weighted vest on lower extremity
      power performance of high school male athletes.
AB  - This study examined lower extremity power performance, using the Margaria-Kalamen
      Power Test, after a dynamic warm-up with (resisted) and without (nonresisted) a
      weighted vest. Sixteen (n = 16) high school male football players, ages 14-18
      years, participated in 2 randomly ordered testing sessions. One session involved
      performing the team's standard dynamic warm-up while wearing a vest weighted at
      5% of the individual athlete's body weight before performing 3 trials of the
      Margaria-Kalamen Power Test. The second session involved performing the same
      dynamic warm-up without wearing a weighted vest before performing 3 trials of the
      Margaria-Kalamen Power Test. The warm-up performed by the athletes consisted of
      various lower extremity dynamic movements over a 5-minute period. No significant
      difference was found in power performance between the resisted and nonresisted
      dynamic warm-up protocols (p > 0.05). The use of a dynamic warm-up with a vest
      weighted at 5% of the athlete's body weight was not advantageous for increasing
      lower extremity power output in this study. The results of this study suggest
      that resisted dynamic warm-up protocols may not augment the production of power
      performance in high school football players.

PMID- 21088551
TI  - Acute effect of upper-body vibration on performance in master swimmers.
AB  - The purpose of the study was to evaluate the effects of regular warm-up, and
      upper-body vibration (UBV), or UBV+ short warm-up on swimming performance in
      Masters Swimmers. Six women and 4 men, mean age 35 +/- 9 years, active master
      swimmers volunteered to participate in the study. Participants were assigned to
      complete 1 of 3 warm-up types: regular, UBV-only, or UBV + short, rest for 3
      minutes, and then completed a 50-yd (45.7 m) freestyle maximal performance time
      trial. The UBV treatment consisted of 5 minutes of upper-body vibration with a
      frequency of 22 Hz. Rating of perceived exertion (RPE) and heart rate (HR) were
      measured post warm-up and post 50-yd time trial. No significant mean differences
      (p = 0.56) were found among regular, UBV-only, or UBV + short warm-ups for 50-yd
      freestyle time (29.1 +/- 3.36, 28.9 +/- 3.39, and 29.1 +/- 3.55 seconds,
      respectively). Individual data indicated that 40% (4/10) of the swimmers swam
      their fastest with UBV-only and 20% (2/10) with UBV + short warm-up compared to
      40% (4/10) with regular warm-up. The RPE pre and post warm-ups did not differ
      significantly (p = 0.059 and p = 0.216, respectively). A significantly higher (p
      = 0.023) HR was observed after regular warm-up compared to UBV + short warm-up.
      Furthermore, HR post 50-yd after regular warm-up was significantly higher
      compared to UBV-only (p = 0.005) and UBV + short warm-up (p = 0.013). The
      findings of the present study indicate that UBV and UBV + short warm-up may be
      considered as addition or an alternative warm-up strategy to regular swimming
      warm-up, producing reduced cardio stress and perceived effort.

PMID- 21088552
TI  - A comparison of trunk muscle activation: Ab Circle vs. traditional modalities.
AB  - The purpose of this study was to compare the activation of the rectus abdominis
      (RA), external oblique abdominis (EO), lower abdominal stabilizers (LASs), and
      lumbar erector spinae (LES) during performance of 3 traditional trunk exercises
      vs. exercise on the Ab Circle device. Surface electromyography was used to assess
      12 subjects (6 men, 6 women) for 6 exercise conditions, including: abdominal
      crunch, side bridge, quadruped, and Ab Circle levels 1-3. For the RA, the
      abdominal crunch elicited significantly greater activity vs. the Ab Circle level
      1, and the side bridge elicited significantly greater activity vs. the Ab Circle
      levels 1 and 2. For the EO, the side bridge elicited significantly greater
      activity vs. the quadruped. No significant differences were noted between
      conditions for the LASs. For the LES, the side bridge and quadruped elicited
      significantly greater activity vs. the abdominal crunch. The results of this
      study indicate that the anterior, posterior, and lateral trunk musculature can be
      activated to similar or even greater levels by performing the 3 traditional trunk
      exercises vs. the Ab Circle. This was particularly evident for the side bridge
      exercise, which elicited significantly greater activity of the RA vs. the Ab
      Circle levels 1 and 2, and elicited similar activity of the EO, LASs, and LES at
      all 3 Ab Circle levels.

PMID- 21088553
TI  - Electromyographic response of the abdominal musculature to varying abdominal
      exercises.
AB  - This study examined the electromyographic (EMG) response of the upper rectus
      abdominis (URA), lower rectus abdominis (LRA), internal obliques (IOs), external
      obliques (EOs), and the rectus femoris (RF) during various abdominal exercises
      (crunch, supine V-up, prone V-up on ball, prone V-up on slide board, prone V-up
      on TRX, and prone V-up on Power Wheel). The subjects (n = 21) performed an
      isometric contraction of the abdominal musculature while performing these
      exercises. Testing revealed no statistically significant differences between any
      of the exercises with respect to the EOs, the URA, or the LRA. However, when
      examining the IO muscle, the supine V-up exercise displayed significantly greater
      muscle activity than did the slide exercise. In addition, EMG activity of the RF
      during the crunch was significantly less than in any of the other 5 exercises.
      These results indicate that when performing isometric abdominal exercises, non
      equipment-based exercises stressed the abdominal muscles similarly to equipment
      based exercises. Based on the findings of the current study, the benefit of
      training the abdominal musculature in an isometric fashion using commercial
      equipment could be called into question.

PMID- 21088555
TI  - How NONPF has helped shape NP education.

PMID- 21088554
TI  - Effect of body cooling on subsequent aerobic and anaerobic exercise performance:
      a systematic review.
AB  - Body cooling has become common in athletics, with numerous studies looking at
      different cooling modalities and different types of exercise. A search of the
      literature revealed 14 studies that measured performance following cooling
      intervention and had acceptable protocols for exercise and performance measures.
      These studies were objectively analyzed with the Physiotherapy Evidence Database
      (PEDro) scale, and 13 of the studies were included in this review. These studies
      revealed that body cooling by various modalities had consistent and greater
      impact on aerobic exercise performance (mean increase in performance = 4.25%)
      compared to anaerobic (mean increase in performance = 0.66%). Different cooling
      modalities, and cooling during different points during an exercise protocol, had
      extremely varied results. In conclusion, body cooling seems to have a positive
      effect on aerobic performance, although the impact on anaerobic performance may
      vary and often does not provide the same positive effect.

PMID- 21088556
TI  - Get to know your legislators.

PMID- 21088557
TI  - Are you protecting patient autonomy?

PMID- 21088559
TI  - Managing chronic pain in acute care.

PMID- 21088562
TI  - Advance care plans for CPR or mechanical ventilation in patients with dementia.
AB  - Early development of advance care plans is an ethical and supportive intervention
      providers can offer patients and families facing a dementia diagnosis.

PMID- 21088563
TI  - Free medical clinics keeping healthcare afloat.
AB  - Free clinics are nonprofit, community-based organizations that provide a variety
      of medical care, including primary care, mental health counseling, and
      pharmaceutical and dental services, at little or no cost to low-income, uninsured
      people.

PMID- 21088564
TI  - Diagnosis and treatment of venous leg ulcers.
AB  - Treatment for venous leg ulcers has been extensively researched and well defined.
      The primary care practitioner who is able to recognize and appropriately treat
      these patients can help prevent months and sometimes years of suffering.

PMID- 21088567
TI  - Is protein metabolism changed with obesity?
AB  - PURPOSE OF REVIEW: Although it is well established that obesity is accompanied by
      various degrees of metabolic impairments especially in the regulation of
      carbohydrate and lipid metabolism, the influence of obesity on protein metabolism
      is not clearly understood. The purpose of this review is to present data
      describing the modification in protein metabolism that have been reported in the
      clinical setting of obesity. RECENT FINDINGS: Recent findings suggest that
      protein metabolism at the whole-body level is less sensitive to insulin action.
      Impairments in skeletal muscle protein synthesis rates in the postabsorptive
      state and in response to anabolic factors are reported in obese human. Finally,
      chronic excessive energy intake and increased adiposity in rats, without the
      appearance of other metabolic disturbances, do not induce any changes in tissue
      protein synthesis rates. SUMMARY: Body composition in obesity is characterized by
      elevated fat mass but also lean body mass which is considered either increased or
      decreased (in the case of sarcopenic obesity). Thus protein metabolism as
      reflected by changes in protein synthesis and breakdown might be modified in
      obese individuals but it is still largely debated. Only a few studies have
      investigated muscle protein kinetics during obesity and do not lead to the same
      conclusions prolonging the controversies. Indeed, obesity is associated with many
      metabolic disturbances which might constitute confounding factors differently
      affecting muscle protein metabolism.

PMID- 21088568
TI  - Branched-chain amino acids in liver disease: new aspects of long known phenomena.
AB  - PURPOSE OF REVIEW: To provide an overview of findings on the role of branched
      chain amino acids (BCAAs) in the pathophysiology, pathobiochemistry, and
      treatment of liver cirrhosis and its complications that have been published since
      or were not included in the last review on this topic in 2007 in this journal.
      RECENT FINDINGS: There has been continued interest in the potential of oral BCAA
      supplements in improving energy metabolism, nitrogen metabolism, carbohydrate
      metabolism, insulin resistance, severity of liver disease, serum albumin levels,
      quality of serum albumin, or postoperative complication rates. Unfortunately,
      many trials suffer from lacking or inadequate controls or small sample size. In a
      fine example of scientific perseverance, Dutch researchers uncovered the long
      known phenomenon of ingested blood being highly comagenic in patients with
      cirrhosis to be due to the low biologic value of blood protein. The absence of
      isoleucine and the abundance of leucine in the hemoglobin molecule by way of BCAA
      antagonism leads to impaired protein synthesis and azotemia paving the way for
      hepatic encephalopathy. SUMMARY: Recognizing hypoisoleucinemia and BCAA
      antagonism following gastrointestinal bleeding, and its successful treatment by
      isoleucine infusion has advanced our understanding of the role of BCAA in liver
      cirrhosis.

PMID- 21088569
TI  - Plasma amino acid imbalance: dangerous in chronic diseases?
AB  - PURPOSE OF REVIEW: In various diseases amino acid imbalances occur which have
      been described especially in the 1980s of the last century. It was noted that
      some of these imbalances may exert specific negative physiological effects.
      However, mainly because of economic reasons, no real attempts have been made to
      develop special amino acid solutions for disease processed associated with amino
      acid imbalances to restore normal amino acid concentrations. RECENT FINDINGS: A
      recent study performed in the fruit-fly Drosophila indicated that modifying the
      amino acid supply may influence both lifespan and fecundity. It was shown that
      adding amino acids but not carbohydrates or fat to a restricted diet decreases
      lifespan. In contrast, administration of certain amino acids especially of
      methionine increased fecundity without decreasing lifespan. It is known that
      dietary restriction can decrease fecundity at the cost of a prolonged lifespan.
      SUMMARY: Recent investigations revealed that amino acids are powerful molecules
      in mediating cell signalling. Therefore, it can be hypothesized that the severe
      amino acid imbalances as observed in uraemia or liver failure may exert a
      relevant impact on various physiologic processes and on organ function. The
      recent results described in Drosophila should stimulate a new research area on
      the effect of amino acid supply in various disease processes.

PMID- 21088570
TI  - Protein metabolism in women and men: similarities and disparities.
AB  - PURPOSE OF REVIEW: To provide an objective and comprehensive review of the recent
      literature addressing the effects of sex on protein metabolism. We also evaluate
      whether these differences can be attributed to physiology or methodology. Because
      of the developmental changes in hormonal milieu and body composition that occur
      across life, the literature has been examined in a longitudinal manner across the
      lifespan. RECENT FINDINGS: Throughout most points of life, men and women of
      similar health status and BMI display fairly similar protein turnover rates.
      However, some investigators have reported sexual dimorphism in protein
      metabolism, which may be partly attributable to differences in fat-free mass
      and/or methodology. In periods of significant changes in the hormonal milieu
      (puberty and menopause), sex differences may become more evident. Finally,
      anabolic stimuli such as feeding and exercise may help highlight any
      discrepancies in protein turnover between men and women. SUMMARY: Sex differences
      in protein metabolism, if any, are most evident during the main phases of
      hormonal changes, and may be also due to differences in body composition.
      However, methodological issues and sample size must be considered when designing
      and evaluating these studies.

PMID- 21088571
TI  - Sarcopenic obesity: satellite cells in the aging muscle.
AB  - PURPOSE OF REVIEW: Current knowledge on satellite cells in relation to suggested
      mechanisms of loss of muscle mass and strength, induction of fat infiltration,
      and countermeasures is highlighted. RECENT FINDINGS: Consensus on the definition
      of sarcopenia and sarcopenic obesity is proposed. Human satellite cell
      heterogeneity has now unequivocally been verified in situ as well as an
      adipogenic potential, though in mice other muscle stem cells are the hot topic to
      induce adipogenesis upon muscle damage. Inflammation, oxidative stress,
      proteolytic degradation, and nuclear apoptosis are discussed as pathogenetic
      mechanisms of sarcopenia, although little evidence exists that they are important
      in human muscle. In rodents, exercise-induced muscle injury is a hallmark for
      sequential events leading to muscle fiber necrosis and sarcopenia. Exercise in
      humans, on the contrary, is the key event to countermeasure sarcopenia. Cautions
      to extrapolate observation in rodents to explain human conditions have been
      presented. SUMMARY: Human satellite cells are indispensable for maintenance of
      human muscle mass, but their implications in the pathogenesis of sarcopenia and
      sarcopenic obesity are still under debate. Nevertheless, satellite cell
      activation upon exercise seems unequivocally together with adequate nutrition to
      be the most effective countermeasure for sarcopenia and sarcopenic obesity.

PMID- 21088572
TI  - Brown adipose tissue and aging.
AB  - PURPOSE OF REVIEW: Brown adipose tissue (BAT) was thought to be a tissue with
      physiological importance early in life (maintenance of body temperature) and to
      disappear after birth. Recent studies using functional imaging have identified
      the presence of BAT activity throughout life. This review focuses on the effect
      of age on BAT function as well as BAT as a potential therapeutic target against
      age-related metabolic diseases. RECENT FINDINGS: The PET/computed tomography
      method likely underestimates the prevalence of BAT because it measures only
      active BAT. The factors underlying the decline of BAT activity with age are
      currently unknown, but likely associated with changes in the activity of the
      sympathetic nervous system and the thyroid axis. Apart from age, the presence of
      active BAT is decreased in males and overweight. The developmental origins of
      brown adipose depots as well as transcription factors involved in their
      differentiation have recently been described. Data suggest that BAT may be
      recruited throughout life. SUMMARY: New imaging techniques may provide more
      accurate estimations of BAT mass in adults. Given its high metabolic rate, it is
      suggested that BAT mass and activity could be activated and thus represent a
      potential target for the management of body weight.

PMID- 21088573
TI  - Nutritional influence on epigenetics and effects on longevity.
AB  - PURPOSE OF REVIEW: This review synthesizes recently published information
      regarding nutrition and its impact upon epigenetically mediated mechanisms
      involved in longevity and aging. RECENT FINDINGS: Recent studies enriched
      considerably our understanding of the relationship between aging and gene
      nutrient interactions that continuously shape our phenotype. Epigenetic
      mechanisms play an important role in mediating between the nutrient inputs and
      the ensuing phenotypic changes throughout our entire life and seem to be
      responsible, in part, for the biological changes that occur during aging. Less is
      known about the epigenetic role that nutrients have in directly influencing
      longevity and aging. However, recent studies clearly indicated that because
      nutrition modulates epigenetic events associated with various diseases (e.g.,
      cancer, obesity, and diabetes), there is at least an indirect epigenetic link
      between nutrition and longevity and, therefore, biologic plausibility to
      hypothesize the epigenetic role of nutrition in altering longevity. Apart from
      limited human studies, promising animal studies brought us much closer to
      understanding how nutrition could have such an impact upon longevity and aging.
      SUMMARY: Complex epigenetic mechanisms are involved in aging and longevity,
      directly or indirectly via disease mechanisms. Nutrition has a strong impact upon
      epigenetic processes and, therefore, holds promise in having important roles in
      regulating longevity and aging.

PMID- 21088574
TI  - Is there an obesity-metabolic syndrome related glomerulopathy?
AB  - PURPOSE OF REVIEW: There is an increasing evidence for a specific form of focal
      segmental glomerulosclerosis (FSGS) related to obesity. Its prevalence has
      progressively increased in past decades. This form of FSGS represents the tip of
      an iceberg: a much broader spectrum of renal malfunction is linked to visceral
      obesity, which is closely connected to, but not completely identical with, the
      concept of 'metabolic syndrome'. RECENT FINDINGS: The obesity-associated FSGS
      (obFSGS) is characterized by massive proteinuria and glomerular lesions which are
      similar to but less pronounced than in idiopathic FSGS, but the long-term
      prognosis is still dubious. The patholophysiology underlying obesity-associated
      renal pathology includes insulin resistance and salt sensitivity of blood
      pressure (BP); more recently adiponectin deficiency, hyperaldosteronism and many
      other pathogenetic factors have been identified. The abnormalities of renal
      structure in obese and morbidly obese individuals include increased kidney
      weight, glomerulomegaly, disorder of podocytes, mesangial expansion and more
      recently also abnormalities of the renal interstitium. This is accompanied by
      functional abnormalities, that is renal hyperperfusion, increased filtration
      fraction and albuminuria. Both obesity and metabolic syndrome have been
      identified as powerful predictors of chronic kidney disease (CKD) and end-stage
      renal disease (ESRD). This correlation is not fully explained by associated
      hypertension and prediabetes/diabetes. SUMMARY: The link between progressive
      kidney disease and visceral obesity is of enormous public health importance.
      Apart from causing obFSGS, obesity aggravates most primary kidney diseases.
      Beyond standard therapy and weight loss, bariatric surgery has recently emerged
      as a successful intervention for obFSGS.

PMID- 21088575
TI  - The story of Notch and chronic kidney disease.
AB  - PURPOSE OF REVIEW: The Notch pathway is an evolutionary conserved cell-cell
      communication mechanism that plays a key role in kidney development. Here, we
      will discuss a number of recently published papers describing the role of Notch
      signaling in kidney development, homeostasis, injury and repair. RECENT FINDINGS:
      Recent gene expression studies identified regulation of the Notch pathway in
      patients with chronic kidney disease (CKD). Mechanistic experiments performed
      using transgenic and knock-out mouse models indicate that Notch plays an
      important functional role in the development of proteinuria and renal fibrosis.
      Inhibition of the Notch pathway ameliorated diabetic kidney disease, nephrotic
      syndrome and fibrosis in different rodent models. SUMMARY: An increasing amount
      of evidence suggests that Notch plays a role in CKD development. Understanding
      the role of Notch signaling in the kidney can aid in the development of new
      therapeutics for CKD.

PMID- 21088576
TI  - SPAK and WNK kinases: a new target for blood pressure treatment?
AB  - PURPOSE OF REVIEW: The regulation of sodium reabsorption by the distal kidney is
      fundamental to blood pressure control. The clinical success of thiazide diuretics
      as antihypertensive drugs underscores the importance of its target, the thiazide
      sensitive sodium/chloride cotransporter (NCC), in this process. However,
      thiazides are often ineffective as monotherapy and have significant side-effects.
      An understanding of NCC regulation at a molecular level may allow the design of
      better tolerated and more effective antihypertensive agents. The aim of this
      review is to provide an overview of the recent developments in the regulation of
      NCC, highlighting a potential new therapeutic target for the treatment of
      hypertension. RECENT FINDINGS: It has been appreciated for several years that WNK
      kinases affect NCC expression, following the discovery that mutations in WNK
      genes cause Gordon syndrome (pseudohypoaldosteronism type II), although the
      precise molecular mechanisms were unclear. What has emerged from further in-vitro
      work is a WNK signalling cascade with the STE20 kinases SPAK and OSR1 as the
      'missing' intermediate kinases that are activated by WNKs. Confirmation that this
      WNK-SPAK cascade operates in vivo comes from work on the phenotype of a kinase
      dead SPAK knockin mouse. This mouse is markedly hypotensive, salt wasting, and
      almost all of its NCC protein in the distal kidney is dephosphorylated. Finally,
      a genome-wide association study has identified an intronic SPAK polymorphism that
      associates with human blood pressure. SUMMARY: SPAK is a recently identified
      regulator of NCC and, hence, sodium reabsorption in the distal nephron. SPAK gene
      variants may also be important players in essential hypertension. If the
      phenotype of the kinase-dead SPAK mouse mimics pharmacological inhibition of this
      kinase, then SPAK is a potentially very interesting new antihypertensive drug
      target.

PMID- 21088578
TI  - Phacoemulsification versus extracapsular cataract extraction: where do we stand?
AB  - PURPOSE OF REVIEW: Cataract surgery at present is divisible into two general
      techniques: manual extracapsular cataract extraction and phacoemulsification-
      with ECCE further separated into the traditional form and small-incision cataract
      surgery. This review will discuss updates in surgical techniques, outcome
      comparisons, cost analysis, and the continued role of extracapsular cataract
      extraction in Western countries. RECENT FINDINGS: Surgical techniques for manual
      extracapsular cataract extraction have undergone much refinement, with numerous
      descriptions of techniques in a recent literature. Studies that have emerged in
      the last several years allow us to compare surgical results between different
      techniques and suggest that there is little difference in final outcome when each
      surgery is done well. Overall cost-effectiveness and suitability of each
      technique vary based on location and facilities. SUMMARY: Manual extracapsular
      cataract extraction (especially small-incision versions) occupies an important
      place in modern cataract surgery, and, while not a replacement for
      phacoemulsification in Western countries, should be part of a cataract surgeon's
      overall skill set.

PMID- 21088577
TI  - Mechanisms and consequences of salt sensitivity and dietary salt intake.
AB  - PURPOSE OF REVIEW: Investigation into the underlying mechanisms of salt
      sensitivity has made important advances in recent years. This review examines in
      particular the effects of sodium and potassium on vascular function. RECENT
      FINDINGS: Sodium chloride (salt) intake promotes cutaneous lymphangiogenesis
      mediated through tissue macrophages and directly alters endothelial cell
      function, promoting increased production of transforming growth factor-beta (TGF
      beta) and nitric oxide. In the setting of endothelial dysfunction, such as occurs
      with aging, diminished nitric oxide production exacerbates the vascular effects
      of TGF-beta, promoting decreased arterial compliance and hypertension. Dietary
      potassium intake may serve as an important countervailing influence on the
      effects of salt in the vasculature. SUMMARY: There is growing appreciation that,
      independently of alterations in blood pressure, dietary intake of sodium and
      potassium promotes functional changes in the vasculature and lymphatic system.
      These changes may protect against development of salt-sensitive hypertension.
      While salt sensitivity cannot be ascribed exclusively to these factors,
      perturbation of these processes promotes hypertension during high-salt intake.
      These studies add to the list of genetic and environmental factors that are
      associated with salt sensitivity, but in particular provide insight into adaptive
      mechanisms during high salt intake.

PMID- 21088579
TI  - Cost-effectiveness of cataract surgery.
AB  - PURPOSE OF REVIEW: To review the changes in the cost-effectiveness of cataract
      surgery in the last few decades. RECENT FINDINGS: Cataract surgery is the
      commonly performed procedure and it has evolved through various techniques,
      namely extracapsular cataract extraction, phacoemulsification and small or
      microincision cataract surgery. In this article we have reviewed the healthcare
      variant analysis, mainly the cost-effectiveness and cost utility over the past
      few years. SUMMARY: Cost-effectiveness implies the economic analysis of relative
      costs and practical outcomes after cataract surgery. Cost utility is typically in
      terms of cost per quality-adjusted life-year gained. Cost-utility values for
      cataract surgery for first eye varied from US$245 to US$22000/QALY in Western
      countries and from US$9 to US$1600 in developing countries. There are two methods
      that have been used to calculate the cost utility namely the costs that are
      discounted at 3% for 12 years and discounted at 3% for 5 years.

PMID- 21088580
TI  - The impact of cataract surgery on quality of life.
AB  - PURPOSE OF REVIEW: This review summarizes the recent literature of the impact of
      cataract surgery from the patient's perspective, with a focus on second
      generation patient reported outcome (PRO) measures that used Rasch analysis to
      explore their data. RECENT FINDINGS: Irrespective of the instrument utilized, the
      overriding conclusion is that cataract surgery unequivocally improves vision
      specific functioning and several aspects of vision-specific quality of life. The
      benefit of cataract surgery, however, on generic health is less clear, due to
      limited vision-related items. Evidence suggests that cataract surgery also
      improves visual functioning in comorbid eye disease, especially in the early
      stages. Similarly, second eye cataract surgery appears to improve visual ability
      beyond that achieved with first eye surgery. Recently, there has been a shift
      toward second-generation, Rasch-validated PROs to assess cataract surgery
      outcomes and large gains in visual function have been demonstrated. Importantly,
      measurement precision is dramatically improved compared with the original first
      generation instruments. SUMMARY: Cataract surgery-induced improvements in visual
      acuity are translated by considerable gains in real life activities, emotional
      and social life components. The utilization of second-generation instruments and
      modern psychometric methods, however, appears to be the best current strategy to
      optimize the impact of cataract surgery on health-related quality of life.

PMID- 21088581
TI  - Are ocular injection anesthetic blocks obsolete? Indications and guidelines.
AB  - PURPOSE OF REVIEW: In this era of topical anesthesia for ocular surgery,
      anesthetic ocular blocks are still important when profound anesthesia and
      akinesia are required. Although injection ocular blocks, retrobulbar and
      peribulbar anesthesia, have been supplanted for most ocular surgery in many
      centers by sub-Tenon's irrigation block because of its superior safety profile,
      still worldwide, injection blocks remain popular. RECENT FINDINGS: We present
      here the results of a survey of the literature published over the last 5 years to
      assess current international preferences for ocular anesthesia injection blocks.
      We discuss the reasons why sub-Tenon's anesthesia is not more universally popular
      and advocate for its greater acceptance because of safety. Specific narrow
      indications for performing injection ocular blocks are presented. Also,
      guidelines for performing retrobulbar anesthesia which reduce the risk of serious
      ocular complications are provided as well as our rationale for preferring
      retrobulbar to peribulbar anesthesia. SUMMARY: Sub-Tenon's block should be
      performed in the operating theatre in preference to retrobulbar or peribulbar
      anesthesia except for limited indications. When injection ocular block is deemed
      necessary, we feel that retrobulbar anesthesia with the technique described may
      be safer than peribulbar anesthesia.

PMID- 21088582
TI  - Assessment of body-image perception and attitudes in obesity.
AB  - PURPOSE OF REVIEW: To examine techniques that have been used to assess various
      aspects of body-image perception and body-image attitudes in obesity. It
      summarizes findings from previous review articles and reports on new research
      findings that have been published between August 2007 and August 2010. RECENT
      FINDINGS: Body-image perception and attitudes in obesity have been assessed using
      questionnaires, figural drawing scales and computer morphing or adjustment
      programs. Most of these techniques have been developed to assess body image in
      eating disorders and as such are not specific to the assessment of body image in
      obesity. SUMMARY: Body-image perception and body-image attitudes are commonly
      assessed in research studies on obesity. However, currently available assessment
      instruments have not been developed specifically for use in obese populations and
      not all have been validated in these populations. Researchers should be careful
      in selecting assessment instruments that are appropriate for use in obesity.

PMID- 21088583
TI  - Dysthymia in a cross-cultural perspective.
AB  - PURPOSE OF REVIEW: Dysthymia is a relatively less-studied condition within the
      spectrum of depressive disorders. New and important information about its status
      has emerged in recent scientific literature. This review highlights some of the
      findings of that literature. RECENT FINDINGS: Even though studies addressing the
      cross-cultural validity of dysthymia are being awaited, results of studies using
      comparable ascertainment procedures suggest that the lifetime and 12-month
      estimates of the condition may be higher in high-income than in low and middle
      income countries. However, the disorder is associated with elevated risks of
      suicidal outcomes and comparable levels of disability whereever it occurs.
      Dysthymia commonly carries a worse prognosis than major depressive disorder and
      comparable or worse clinical outcome than other forms of chronic depression.
      Whereas there is some evidence that psychotherapy may be less effective than
      pharmacotherapy in the treatment of dysthymia, the best treatment approach is one
      that combines both forms of treatment. SUMMARY: Dysthymia is a condition of
      considerable public health importance. Our current understanding suggests that it
      should receive more clinical and research attention. Specifically, the
      development of better treatment approaches, especially those that can be
      implemented in diverse populations, deserves research attention.

PMID- 21088584
TI  - Response to treatment in bipolar disorder.
AB  - PURPOSE OF REVIEW: Bipolar disorder is a complex psychiatric condition that has
      been shown to carry a great degree of genetic loading. This review addresses
      current research in the genetics of treatment response in bipolar disorder, with
      a focus on findings that have shaped our understanding of the changing direction
      of this field in light of recent technological advancements. RECENT FINDINGS: The
      recent publications in bipolar disorder treatment response have helped
      consolidate or improve upon knowledge of susceptibility loci and genes in the
      field. There seems to be an increasing trend toward functionally assessing the
      role played by putative candidate genes and molecular factors modulating
      expression in bipolar disorder, as well as a movement toward more global, pathway
      and genome-wide-oriented research. SUMMARY: Genetic and molecular research to
      date in bipolar disorder treatment response has not completely answered all the
      lingering questions in the field, but has contributed to the development of a
      more patient-based understanding of treatment. In order to apply these findings
      at a clinical level, more comprehensive treatment response studies are
      imperative, combining recent advances in high-throughput genomics with functional
      molecular research.

PMID- 21088585
TI  - Imaging in posttraumatic stress disorder.
AB  - PURPOSE OF REVIEW: Posttraumatic stress disorder (PTSD) is an unusual diagnosis
      in requiring an external environmental stressor to be present, in addition to the
      conventional signs and symptoms. Early controversies surrounded the validity of
      its criteria and whether there was a common neural basis for this disorder. This
      review summarizes recent neuroimaging studies, which have begun to clarify the
      basis of PTSD by combining imaging data with investigations of the stress
      response, and by employing fear and extinction learning paradigms to probe the
      underlying neural changes in those with the disorder. RECENT FINDINGS: We examine
      the recent literature with three main aims. First, to assess whether structural
      changes in PTSD are causal of or secondary to the condition. Second, to summarize
      current understanding of the relationship between neural activation and the
      stress responses within the autonomic nervous system in PTSD patients and
      controls. Finally, we examine neural mechanisms underlying the response to fear
      and reward, demonstrating how these are altered in PTSD. SUMMARY: A greater
      understanding of the brain mechanisms underlying healthy responses to fear and
      stress, and their alterations in PTSD, has opened up a new spectrum of possible
      pharmacological agents by which to approach to PTSD therapy and has begun to
      reveal the neural processes underlying the common failure of response to current
      treatments.

PMID- 21088586
TI  - Second-generation antipsychotics in major depressive disorder: update and
      clinical perspective.
AB  - PURPOSE OF REVIEW: The aim of this systematic review was to examine the efficacy
      and safety of second-generation antipsychotics (SGAs) in nonpsychotic major
      depressive disorder (MDD). RECENT FINDINGS: In MDD, SGA monotherapy or adjunctive
      therapy to conventional antidepressants showed rapid onset of antidepressant
      efficacy. Although maintenance data are limited, quetiapine monotherapy,
      risperidone adjunctive therapy, and amisulpride adjunctive therapy significantly
      delayed the time to relapse as compared with placebo. In general, extrapyramidal
      symptoms appeared to be low with SGAs, but a higher incidence of akathisia was
      observed with aripiprazole. An elevated risk of weight gain was observed with
      olanzapine-fluoxetine combination, risperidone, aripiprazole, and quetiapine
      compared with placebo. At present, there are insufficient data to confidently
      distinguish between different SGAs in the treatment of MDD. A recent meta
      analysis found that adjunctive SGAs were significantly more effective than
      placebo, but differences in efficacy were not identified among the studied
      agents, nor were outcomes affected by trial duration or the method of
      establishing treatment resistance. SUMMARY: Both SGA monotherapy and adjunctive
      therapy showed greater efficacy in the treatment of MDD than placebo, but
      augmentation is more widely utilized in treatment-resistant depression.
      Clinicians should routinely monitor for cardiometabolic side-effects and
      extrapyramidal symptoms during SGA therapy.

PMID- 21088587
TI  - Drug treatment for mood disorders in pregnancy.
AB  - PURPOSE OF REVIEW: During the last few years, several researches, often showing
      contradictory findings, have investigated the safety of psychotropic medications
      used for treating mood disorders in pregnancy. Hence, the necessity exists to
      update this information constantly in order to ensure the safest option for the
      mother-infant pair. RECENT FINDINGS: The risk of fetal anomalies associated with
      early in-utero exposure to antidepressants seems to be increased after paroxetine
      and clorimipramine exposure, whereas prenatal exposure to nearly all
      antidepressants is linked to the potential onset of the Prenatal Antidepressant
      Exposure Syndrome. As regards classic mood stabilizers, the teratogenic risk
      historically reported with lithium should probably be softened, whereas valproate
      is the medication which shows the strongest association with fetal anomalies. An
      increased risk of autism-spectrum disorders and infant neurodevelopmental delay
      is also associated with valproate exposure through the placenta. No significant
      reproductive safety data are available on atypical antipsychotics, although such
      medications may indirectly increase the rate of fetal malformation by inducing
      gestational diabetes. SUMMARY: Avoiding the use of clorimipramine, paroxetine,
      valproate, and atypical antipsychotics during pregnancy is advisable. However,
      when starting or continuing pharmacological treatment during pregnancy,
      clinicians should consider not only the intrinsic iatrogenic risk of birth
      defects or perinatal complications, but also the general safety profile for the
      expectant mother. Indeed, specific adverse reactions (such as nausea, vomiting,
      constipation, and excessive weight gain) may aggravate the classic clinical
      findings of pregnancy, thus indirectly facilitating the occurrence of pregnancy
      complications and fetal and neonatal problems.

PMID- 21088588
TI  - A Swiss anaesthesiology closed claims analysis: report of events in the years
      1987-2008.
AB  - BACKGROUND AND OBJECTIVE: In 1999, the Swiss Society of Anaesthesiology and
      Reanimation (SSAR) initiated an analysis of closed malpractice claims filed
      against anaesthetists in a project intended to improve patient safety. This
      article discusses the results of a review of closed claims between 1987 and 2008
      and filed up to the end of 2009. METHODS: Records of closed claims were provided
      by Swiss professional medical liability insurance companies and the Office for
      Extrajudicial Expert Review of the Swiss Medical Association. Data were collected
      by an onsite reviewer, converted into a standardised format and sent to the SSAR
      Closed Claims Study Group.Assessment criteria employed by the committee were
      level of care (standard or substandard); severity of injury; appropriateness of
      patient information; and consent. RESULTS: The records of 171 events leading to
      anaesthesia-related injuries were entered into the database. These injuries
      occurred within the period 1987-2008. The majority of claims (54%) were related
      to regional anaesthesia, with general anaesthesia accounting for 28% and other
      anaesthesia-related procedures for 18%. The quality of care was judged by the
      committee to be substandard in 55% of cases, and liability was accepted in 46% of
      all claims. Negative outcomes were death in 12% and permanent injury in 63% of
      the patients. CONCLUSION: The closed claims analysis project enabled the SSAR to
      identify areas of high medicolegal risks to gain an insight into the causes of
      infrequent but potentially harmful events leading to anaesthesia-related injuries
      and, based on these data, to develop preventive strategies.

PMID- 21088589
TI  - The anaesthetist makes a difference: the bottom line matters!

PMID- 21088590
TI  - Evidence for the efficacy of acupressure for preventing post-operative nausea and
      vomiting: an ongoing debate.

PMID- 21088591
TI  - Use of a temporary forearm tourniquet for intravenous regional anaesthesia: a
      randomised controlled trial.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effect of a temporary, additional
      mid-forearm tourniquet on the quality of intravenous regional anaesthesia.
      METHODS: Fifty patients undergoing hand and wrist surgery under intravenous
      regional anaesthesia (Bier's block) were randomised to receive a temporary mid
      forearm tourniquet for 8 min during and after administration of local anaesthetic
      or to a control group (no tourniquet). The dose of prilocaine was standardised.
      Onset of block was assessed by response to pinprick in ulnar, radial and median
      nerve distributions of the hand. Quality of intraoperative anaesthesia was
      assessed using response to forceps pinch, visual analogue score (VAS) for pain
      and requirement for supplemental infiltration anaesthesia. Post-operative pain
      was assessed using VAS. RESULTS: There was no difference between the groups with
      respect to intraoperative pain VAS (P = 0.19) or post-operative pain VAS (P =
      0.69). More patients in the temporary tourniquet group were numb to pinprick
      testing in the three nerve distributions of the hand at 4 and 8 min after
      injection of local anaesthetic (P = 0.038). There was no difference in the
      requirement for supplemental infiltration of local anaesthetic between the
      groups. CONCLUSION: Our results suggest that a temporary mid-forearm tourniquet
      might speed the onset of intravenous regional anaesthesia. Although the advantage
      is lost by the time surgery starts, the technique might permit the use of a
      smaller dose of local anaesthetic and may have safety advantages by more rapid
      movement of anaesthetic out of the venous bed. The technique merits further
      investigation.

PMID- 21088593
TI  - Validation of a model of graded difficulty in Laerdal SimMan: functional
      comparisons between Macintosh, Truview EVO2, Glidescope Video Laryngoscope and
      Airtraq.
AB  - BACKGROUND AND OBJECTIVE: A randomised, cross-over study was designed to validate
      a new model of graded difficulty (based on mandibular space reduction) in the
      Laerdal 'SimMan' mannnequin and to suggest functional comparisons between
      Macintosh. Glidescope Video Laryngoscope, Truview EVO2 and Airtraq. METHODS:
      Twenty anaesthetists attempted intubation with all four laryngoscopes in three
      settings: easy, intermediate (based on a custom-made removable prosthetic insert)
      and difficult ('tongue oedema', a mannnequin feature). Laryngoscopic view and
      time to intubate were the primary outcome measures. Other measures were
      successful intubation, ease of laryngoscopy [visual analogue scale (VAS)] and
      intubation (VAS), tongue compression score and number of attempts. RESULTS:
      Between settings comparisons demonstrated that Macintosh, Glidescope and Airtraq
      had worsening scores from easy to intermediate with lesser changes for Truview.
      However, with the intermediate to difficult comparison, Airtraq was the only
      blade with no worsening of scores. Within-blade comparisons showed that Macintosh
      was superior over all in both the easy and intermediate settings, whereas Airtraq
      was the most successful blade in the difficult setting. CONCLUSION: Our study
      suggests that Glidescope and, to some extent Truview, are functionally similar to
      Macintosh and suffer from similar limitations in the difficult setting. On the
      contrary, Airtraq was functionally unique in providing good laryngeal exposure in
      the difficult setting and without excessive tongue compression.

PMID- 21088592
TI  - Effect of auditory evoked potential-guided anaesthesia on consumption of
      anaesthetics and early postoperative cognitive dysfunction: a randomised
      controlled trial.
AB  - BACKGROUND: Post-operative cognitive dysfunction (POCD) after non-cardiac surgery
      is a well known problem in some categories of patients. This study aims to
      evaluate the influence of auditory evoked potential (AEP)-guided anaesthesia on
      the requirement for anaesthetic drugs and their influence on POCD. METHODS: Four
      hundred and fifty patients aged between 18 and 92 years scheduled for ophthalmic
      surgery under general anaesthesia were assigned randomly to one of two groups. In
      group A (AEP group), the depth of anaesthesia (DoA) was aimed at an AEP index
      (AAI) between 15 and 25. In group C (control group), DoA was guided by clinical
      signs. Hypotension was treated with fluids and vasopressors using a standardised
      algorithm. A mini-mental test and the Cognitive Failure Questionnaire were used
      to evaluate cognitive function. RESULTS: Anaesthetic drug requirements were
      significantly lower in group A than in group C: propofol 92.5 +/- 26.5 vs. 103.8
      +/- 39.5 mg (P = <0.001) and desflurane end-tidal concentration 2.5 +/- 0.58 vs.
      3.3 +/- 0.79% (P < 0.001). In group A, 36 patients (16%) received additional
      fluids and vasopressors compared to 65 patients (29%) in group C (P < 0.01). AAI
      values differed significantly between the groups: 18 (11-21) in group A vs. 12
      (10-19) in group C (P < 0.001). The number of patients with POCD was 16 in group
      C compared to two in group A (P < 0.001) at day 1 post-operation. CONCLUSION: AEP
      monitoring allows dose reduction of anaesthetic agents, leading to better
      cardiovascular stability and decreased requirements for intra-operative fluids
      and vasopressors. Cognitive decline seen following minor ophthalmic surgery, even
      when anaesthesia is assessed clinically, is short-lived with no long-term
      sequelae.

PMID- 21088594
TI  - Training in placement of the left-sided double-lumen tube among non-thoracic
      anaesthesiologists: intubation model simulator versus computer-based digital
      video disc, a randomised controlled trial.
AB  - OBJECTIVES: To compare the effectiveness of training with an airway model
      simulator versus digital video disc (DVD)-based instruction in placement of
      double-lumen endotracheal (DLT) tubes by anaesthesiologists with limited thoracic
      experience. DESIGN: Single academic centre parallel randomised controlled trial
      with computer-generated random allocation. PARTICIPANTS: Sixty patients
      undergoing elective thoracic or oesophageal surgeries requiring one-lung
      ventilation. Twenty-seven non-thoracic anaesthesiologists were randomised to
      place a DLT. INTERVENTION: DLT placement instruction by an interactive airway
      simulator or computer-based DVD training. The main outcome measure was successful
      DLT placement. RESULTS: Twenty-seven anaesthesiologists were randomised to one of
      the two intervention groups. Sixty consecutive patients were assigned to a
      randomised anaesthesiologist (n = 30 in each group). Participants failed to
      correctly place or position the DLT tubes in 14 of 60 patients (failure rate of
      23%). There was no difference in the probability of satisfactory placement or
      time for positioning of the DLT between the training groups; 80.5% (95%
      confidence interval 58.2-96.2%) of tubes were successfully placed following
      intubation model simulator training versus 73.6% (95% confidence interval 49.8
      88.5%) in the DVD group (P = 0.378). CONCLUSION: Both teaching methods had
      similar outcomes for placement of DLTs by anaesthesiologists with limited
      thoracic anaesthesia experience. Both groups performed better than individuals in
      our prior study. Therefore, these methods should be considered when training
      anaesthesiologists to successfully place DLTs.

PMID- 21088595
TI  - The head-down tilt position decreases vasopressor requirement during hypotension
      following induction of anaesthesia in patients undergoing elective coronary
      artery bypass graft and valvular heart surgeries.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have failed to demonstrate that the
      head-down tilt position confers benefits in hypovolaemic hypotensive patients.
      The aim of this study was to evaluate the haemodynamic effect and vasopressor use
      by this position in hypotensive patients after the induction of general
      anaesthesia. METHODS: This prospective randomised study involved 98 patients
      scheduled for elective cardiac surgery and 40 patients (40.1%) developed
      hypotension after anaesthesia induction. Upon occurrence of hypotension, patients
      were randomly allocated to the supine (n = 19) or head-down tilt (n = 21) groups
      (15 degrees  head-down tilt position). Blood pressure, heart rate, cardiac index
      and stroke volume index were recorded at 1-min interval for 10 min from the
      occurrence of hypotension. Vasopressors were administered to treat hypotension in
      both groups. RESULTS: No haemodynamic difference was observed between the supine
      and head-down tilt groups except for SBP changes from baseline at 1 min (-3.98 +/
      6.31 vs. 1.84 +/- 8.25%, P = 0.004) and 2 min (1.51 +/- 14.34 vs. 9.37 +/-
      10.57%, P = 0.032). The number of vasopressor administrations and percentage of
      the patients requiring vasopressors in the supine group were greater than that in
      the head-down tilt group [median 1 (range 1-5) vs. median 0 (range 0-2), P =
      0.002, 19/19 (100%) vs. 10/21 (47.6%), P < 0.001]. CONCLUSION: The head-down tilt
      position in hypotensive patients following anaesthesia induction reduced
      vasopressor requirement by almost one third. Minimal haemodynamic effect may be
      caused by different vasopressor administrations. This result suggests that the
      head-down tilt position may enable more stable anaesthesia induction in patients
      undergoing elective coronary artery bypass graft or valvular heart surgeries.

PMID- 21088596
TI  - Pulse pressure variation as a predictor of fluid responsiveness during one-lung
      ventilation for lung surgery using thoracotomy: randomised controlled study.
AB  - BACKGROUND AND OBJECTIVE: Pulse pressure variation (PPV) is increasingly
      advocated as a predictor of fluid responsiveness in patients receiving mechanical
      ventilation. However, the ability of PPV has never been studied during one-lung
      ventilation (OLV). Therefore, we evaluated the value of PPV to predict fluid
      responsiveness in patients receiving conventional and protective OLV using
      receiver operating characteristic (ROC) analysis, respectively. METHODS: Forty
      nine patients undergoing lung surgery requiring OLV were enrolled in this study.
      Patients were randomised either to group P [patients receiving protective OLV
      with tidal volume 6 ml kg, inspired oxygen fraction (FIO2) of 0.5 and positive
      end-expiratory pressure (PEEP) of 5 cmH2O) or group C (patients receiving
      conventional OLV with tidal volume of 10 ml kg, FIO2 of 1.0 and no PEEP).
      Following OLV, PPV and cardiac output were measured before and 12 min after fluid
      loading (7 ml kg hydroxyethyl starch 6%). Patients whose cardiac indices
      increased by at least 15% to fluid loading were defined as the responders.
      RESULTS: The areas under ROC curve for PPV were 0.857 (P = 0.006) in group P and
      0.524 (P = 0.839) in group C, respectively. The optimal threshold value given by
      ROC analysis for PPV was 5.8% in group P. CONCLUSIONS: PPV could predict fluid
      responsiveness only during protective OLV, but not conventional OLV. PPV would be
      helpful for fluid management in patients receiving protective OLV for lung
      surgery using thoracotomy.

PMID- 21088597
TI  - Current approach to the haemodynamic management of septic shock patients in
      European intensive care units: a cross-sectional, self-reported questionnaire
      based survey.
AB  - BACKGROUND AND OBJECTIVE: The aim of this survey was to investigate clinicians'
      current approach to the haemodynamic management and resuscitation endpoints in
      septic shock. METHODS: This cross-sectional, self-reported questionnaire-based
      survey was sent to the clinical director of selected ICUs in 16 European
      countries. The questionnaire consisted of two parts and 25 questions. The first
      part retrieved general information on the hospital and ICU, and the second part
      of the questionnaire collected detailed information on the approach to
      haemodynamic management of septic shock. RESULTS: Of 481 clinicians invited to
      participate, 237 (49.3%) responded. Ninety-two questionnaires were excluded
      because of more than 20% missing responses, rendering 145 (30.1%) for statistical
      analysis. Administration of albumin (P = 0.007), gelatine preparations (P =
      0.002), Ringer's solution (P = 0.02) and isotonic saline (P = 0.001) for fluid
      resuscitation varied between respondents from different countries. Further
      differences between respondents from different countries were observed for the
      choice of the first-line inotropic drug (P < 0.001), use of supplementary
      vasopressin (P = 0.02), supplementary fludrocortisone (P = 0.05) and measurement
      of cardiac output with the transpulmonary thermodilution (P = 0.001), lithium
      dilution (P = 0.004) and oesophageal Doppler (P = 0.005) technique. Mean arterial
      blood pressure (87%), central venous oxygen saturation (65%), central venous
      pressure (59%), systolic arterial blood pressure (48%), mixed venous oxygen
      saturation (42%) and cardiac index (42%) were the six haemodynamic variables most
      commonly claimed to be used as resuscitation endpoints. CONCLUSION: The current
      approach to the haemodynamic management of septic shock patients in a selected
      cohort of European ICU clinicians is in agreement with the Surviving Sepsis
      Campaign guidelines with the exception of the haemodynamic goals.

PMID- 21088599
TI  - Diltiazem poisoning treated with hyperinsulinemic euglycemia therapy and
      intravenous lipid emulsion.
AB  - Intravenous lipid emulsion (ILE) has been proposed as a rescue therapy for severe
      local anesthetic drugs toxicity, but experience is limited with other lipophilic
      drugs. An 18-year-old healthy woman was admitted 8 h after the voluntary
      ingestion of sustained-release diltiazem (3600 mg), with severe hypotension
      refractory to fluid therapy, calcium salts, and high-dose norepinephrine (6.66
      MUg/kg/min). Hyperinsulinemic euglycemia therapy was initiated and shortly after
      was followed by a protocol of ILE (intralipid 20%, 1.5 ml/kg as bolus, followed
      by 0.25 ml/kg over 1h). The main finding attributed to ILE was an apparent rapid
      decrease in insulin resistance, despite a prolonged serum diltiazem elimination
      half-life. Diltiazem is a lipophilic cardiotoxic drug, which could be sequestered
      in an expanded plasma lipid phase. The mechanism of action of ILE is not known,
      including its role in insulin resistance and myocardial metabolism in calcium
      channel blocker poisoning.

PMID- 21088598
TI  - A randomised trial comparing sufentanil versus remifentanil for laparoscopic
      gastroplasty in the morbidly obese patient.
AB  - BACKGROUND AND OBJECTIVE: This prospective, randomised double-blind study
      compared the effects of target control infusion (TCI) of sufentanil and
      remifentanil on the quality of recovery and post-operative pain control in
      morbidly obese patients undergoing laparoscopic gastroplasty. METHODS: Following
      institutional Ethics Committee approval and written informed consent, 100
      morbidly obese patients were randomised to receive either TCI sufentanil (0.3 ng
      ml-1; S-group; N = 50) or TCI remifentanil (3 ng ml-1; R-group; N = 50) in
      combination with desflurane (O2/air mixture: FiO2, 50%). Quality of recovery was
      estimated by means of the modified Aldrete score and by the ability to perform
      psychomotor tests with the same competence post-operatively as pre-operatively.
      Post-operative pain was evaluated by the quantity of piritramide needed to
      achieve a visual analogue scale (VAS) less than 3. Statistical analysis was
      performed using an unpaired Student's t-test, Mann-Whitney U-test and chi2 test,
      as appropriate. RESULTS: Patient and surgical characteristics were similar among
      groups. In the R-group, time to extubation was significantly shorter, but VAS
      significantly higher than that in the S-group (P < 0.01). Quality of recovery and
      duration of post-anaesthesia care unit stay were comparable between groups (S
      group: 119 +/- 27 min and R-group: 119 +/- 35 min). Piritramide consumption
      during the first 4 post-operative hours was higher in the R-group than in the S
      group [S-group (median, range): 11.5 mg, 5.5-16.0; R-group: 18.0 mg, 14-22, P <
      0.01], but not later on. CONCLUSION: In the conditions of the present study,
      although TCI sufentanil resulted in slower awakening than TCI remifentanil, it
      was associated with a better quality of recovery.

PMID- 21088600
TI  - Expression of placental growth factor in regenerating livers after partial
      hepatectomy in the rat.
AB  - BACKGROUND/AIMS: Placental growth factor (PlGF) is known for its role in
      pathological conditions to protect parenchymal cells of different organs from
      injury, whereas its presence in the liver and its potential importance in
      stimulating liver regeneration has never been described. This was investigated in
      this study using a rat model of partial hepatectomy (PH). METHODS: The rat model
      of 70, 80, and 90% PH was used. Liver samples were taken peroperatively, 1 h, 1,
      2, 3, and 7 days after surgery. Liver regeneration was evaluated by liver
      weight/body weight ratio, liver regeneration rate (%), and proliferating cell
      marker Ki67. The expression of PlGF, vascular endothelial growth factor (VEGF),
      VEGF receptor 1 (Flt-1), VEGF receptor 2 (Flk-1), and hypoxia inducible factor
      1alpha mRNA was measured by quantitative real-time PCR and localized by
      immunohistochemistry. RESULTS: The mRNA expression of PlGF was upregulated
      immediately after PH. Compared with 70 and 80% PH groups, the 90% PH group had a
      significantly lower PlGF and hypoxia inducible factor-1alpha mRNA expression, in
      parallel to a delayed liver weight/body weight ratio recovery. Only little
      differences were observed in VEGF, Flt-1, and Flk-1 mRNA expression among the PH
      groups. CONCLUSION: This study shows for the first time the PlGF upregulation in
      regenerating livers, which is related to hypoxia stimulation and liver growth.
      The swift PlGF upregulation immediately after PH may indicate an important role
      for the PlGF/Flt-1 pathway in the early stage of liver regeneration.

PMID- 21088601
TI  - A role for myokines in muscle-bone interactions.
AB  - This review presents the hypothesis that muscle is a source of secreted factors
      (myokines) that can influence bone mass in both positive and negative ways.
      Growth factor secretion by muscle may therefore be one pathway through which
      mechanical signals are transduced biologically.

PMID- 21088602
TI  - Biomechanics of sport concussion: quest for the elusive injury threshold.
AB  - Previous concussion biomechanics research has relied heavily on the animal model
      or laboratory reconstruction of concussive injuries captured on video footage.
      Real-time data collection involves a novel approach to better understanding the
      medical issues related to sport concussion. Recent studies suggest that a
      concussive injury threshold is elusive and may, in fact, be irrelevant when
      predicting the clinical outcome.

PMID- 21088603
TI  - Aging, persistent viral infections, and immunosenescence: can exercise "make
      space"?
AB  - Overcrowding the immune space with excess clones of viral-specific T cells causes
      the naive T-cell repertoire to shrink, which increases infection susceptibility
      to novel pathogens. Physical exercise preferentially mobilizes senescent T cells
      from the peripheral tissues into the blood, which might facilitate their
      subsequent apoptosis and create "vacant space" for newly functional T cells to
      occupy and expand the naive T-cell repertoire.

PMID- 21088604
TI  - Heat shock proteins are important mediators of skeletal muscle insulin
      sensitivity.
AB  - Endogenous heat shock proteins (HSP) are decreased in disease states associated
      with insulin resistance and aging. Induction of HSPs has been shown to decrease
      oxidative stress, inhibit inflammatory pathways, and enhance metabolic
      characteristics in skeletal muscle. As such, HSPs have the potential to function
      as an important defense system against the development of insulin resistance and
      type 2 diabetes.

PMID- 21088606
TI  - Why do older sprinters reach the finish line later?
AB  - Slowing of movement with aging is inevitable. The mechanisms responsible for this
      deterioration, however, remain poorly understood. Changes to physiological and
      mechanical factors controlling muscle force and power production seem likely
      contributors, but a reduced ability for fast transmission of the force to the
      skeleton also may contribute to the deterioration in performance.

PMID- 21088605
TI  - Sex differences: implications for the obesity-asthma association.
AB  - We have demonstrated in several studies that obesity and adipokines are more
      strongly associated with asthma in women than in men. The reason for this
      controversial sex difference is not known. Based on our previous studies, we
      hypothesize that sex-related differences in ectopic fat may explain the obesity
      asthma association in women.

PMID- 21088607
TI  - Effect of thermal stress on cardiac function.
AB  - Whole-body heating decreases pulmonary capillary wedge pressure and cerebral
      vascular conductance and causes an inotropic shift in the Frank-Starling curve.
      Whole-body cooling increases pulmonary capillary wedge pressure and cerebral
      vascular conductance without changing systolic function. These and other data
      indicate that factors affecting cardiac function may mechanistically contribute
      to syncope during heat stress and improvements in orthostatic tolerance during
      cold stress.

PMID- 21088608
TI  - Efficacy and safety of treatments for refractory generalized anxiety disorder: a
      systematic review.
AB  - This study systematically collated clinical evidence on refractory generalized
      anxiety disorder (GAD). Refractory GAD patients are those who have failed to
      respond adequately to at least one earlier treatment for GAD. MEDLINE, EMBASE,
      The Cochrane Library and conference proceedings were searched to identify trials.
      Four placebo-controlled trials (pregabalin, olanzapine, quetiapine, risperidone)
      and four single-arm studies (aripiprazole, risperidone, quetiapine, ziprasidone)
      evaluated the add-ons to initial treatment(s) or switch of treatment(s) because
      of inadequate efficacy. The most robust trial was the pregabalin study, with a
      study duration of 8 weeks and a largest sample size that consists of 356
      patients. A significant reduction in the Hamilton Anxiety Scale (HAM-A) score was
      found for pregabalin and risperidone augmentation compared with placebo.
      Olanzapine augmentation resulted in a significantly higher proportion of
      responders (using HAM-A scores) compared with placebo. Quetiapine augmentation
      did not result in significantly greater mean reductions in the HAM-Ascores
      compared with placebo. There is a need for effective and safe augmentation
      treatments for patient's refractory to initial treatments for GAD. This study has
      located one large robust trial assessing the add-on to pregabalin. All other
      trials were small and unpowered studies with less than 50 patients. Further high
      quality trials of augmentation treatment on refractory GAD are required.

PMID- 21088609
TI  - Changes of excitability in M1 induced by neuromuscular electrical stimulation
      differ between presence and absence of voluntary drive.
AB  - The aim of this study is to investigate excitability changes in the human motor
      cortex induced by variable therapeutic electrical stimulations (TESs) with or
      without voluntary drive. We recorded motor-evoked potentials (MEPs) from extensor
      and flexor carpi radialis (FCR) muscles at rest and during FCR muscle contraction
      after the application of TES on FCR. TES application conditions were changed
      intensities, frequencies, and trains. In addition, to evaluate the contribution
      of M1 inhibitory circuits to the effects of TES application, we also recorded
      MEPs using paired-pulse transcranial magnetic stimulation. In resting muscle
      states, an increase in TES intensity resulted in an increase in MEP ratio in both
      the muscles. In contrast, when TES was applied to FCR during contraction, MEP
      ratios of both the muscles decreased with increased number of pulse trains.
      However, under both the states, MEP ratios decreased induced by paired-pulse
      transcranial magnetic stimulation in extensor carpi radialis to which TES was not
      applied. Excitability changes in M1 induced by TES application were reversibly
      modulated depending on the presence or absence of voluntary drive. This study
      showed that the therapy and the voluntary drive of the target muscles act
      together, and complement the effects of each other, which may be beneficial for
      optimizing the rehabilitation if the therapy accompanies voluntary drive.

PMID- 21088610
TI  - Vocational rehabilitation in Wales: a mixed method evaluation of condition
      management programmes.
AB  - Condition management programmes (CMPs) are vocational rehabilitation schemes,
      which aim to address the needs of disability-related benefit claimants in the UK.
      The aim of this evaluation was to investigate the extent to which three CMPs in
      Wales enable individuals to manage health conditions and move closer towards
      work. Outcome measurements for the Short Form 36 Version 2, General Self Efficacy
      Scale and Hospital and Anxiety and Depression Scale were collated from 244
      clients and analyzed using parametric statistics. Semistructured interviews were
      also held with members of staff and clients (n=27). Statistically significant
      changes (P<0.001) were observed in all outcome measure scores between start and
      end of intervention. Benefits of engaging in CMPs included better management of
      health conditions, increased confidence and increased activity. The results
      suggest that CMPs may be particularly effective for those with mental health
      conditions and support a model of vocational rehabilitation that focuses upon
      concepts such as fulfilment and a positive sense of identity.

PMID- 21088611
TI  - The ICF and postsurgery occupational therapy after traumatic hand injury.
AB  - Recent studies have examined the effectiveness of hand rehabilitation programmes
      and have linked the outcomes to the concept of ICF but not to specific ICF
      category codes. The objective of this study was to gain experience using ICF
      concepts to describe occupational therapy interventions during postsurgery hand
      rehabilitation, and to describe improvement in functioning using ICF categories.
      In addition, investigated was the agreement between the ICF categories for
      occupational therapy interventions and the outcome measures used. Fifteen
      patients with traumatic hand injuries agreed to participate. Outcome measures
      were used to assess the following variables: range of motion, grip strength, pain
      intensity, upper-extremity functioning and health-related quality of life.
      Analysis of variance for repeated measures was used between the measures at
      baseline and at 3-month and 12-month follow-ups. The results showed that a
      pattern of occupational therapy interventions concerning body functions and body
      structures, activities and environmental factors could be identified during the
      early postsurgery phase and for interventions at participation level during the
      later phase. Agreement between occupational therapy interventions and outcome
      measures was found for 11 pairs. Three of the pairs concerned body function and
      eight were at the activity and participation level. During the rehabilitation
      process, the majority of improvements took place between baseline and the 3-month
      follow-up. We concluded that ICF categories can be used to describe occupational
      therapy interventions in postsurgery hand rehabilitation after trauma; that the
      use of ICF as a reference framework provides a clear picture of which health
      domains are addressed; and that a consistent use of ICF categories facilitates
      linking between rehabilitation interventions and outcome assessments, thereby
      increasing the possibility of showing the effects of these interventions.

PMID- 21088612
TI  - Explanatory case study design--a clarification.

PMID- 21088613
TI  - Split-thickness skin graft harvested with saline moistening.

PMID- 21088614
TI  - Burn caused by pressure cookers.

PMID- 21088615
TI  - Curcumin reduces injury progression in a rat comb burn model.
AB  - The oriental spice curcumin has anti-inflammatory and antioxidant effects. When
      given orally before injury, curcumin reduces burn progression in a rat comb burn
      model. The authors hypothesized that intravenous administration of curcumin after
      injury would reduce burn progression and that its effects are mediated through
      iron chelation. Two comb burns were created on the dorsum of Sprague-Dawley rats
      (weight, 300 g) using a brass comb with four rectangular prongs preheated in
      boiling water and applied for 30 seconds resulting in four rectangular 10 * 20 mm
      full-thickness burns separated by three 5 * 20 mm unburned interspaces (zone of
      ischemia). Animals were randomized to receive one of four doses of crude curcumin
      or one of six doses of purified curcumin intravenously 1 and 24 hours after
      injury. Another set of animals were randomized to deferoxamine or control
      vehicle. Wounds were observed at 7 days after injury for visual evidence of
      necrosis in the unburned interspaces. Full-thickness biopsies from the
      interspaces were evaluated with Hematoxylin and Eosin staining 7 days after
      injury for evidence of necrosis. The percentage of unburned interspaces
      undergoing necrosis at 1 week by purified curcumin doses was 0 MUg/kg, 74%; 0.3
      MUg/kg, 58%; 1 MUg/kg, 53%; 3 MUg/kg, 37%; 10 MUg/kg, 63%; 30 MUg/kg, 53%; and
      100 MUg/kg, 26%. The differences among the groups were significant (P = .03).
      When compared with controls, the 1 and 3 MUg/kg curcumin treatment groups had
      significantly less progression of interspaces to necrosis (P = .04 and .002) as
      did the 30 and 100 MUg/kg treatment groups (P = .03 and <.001). Deferoxamine did
      not reduce burn progression. When administered intravenously 1 and 24 hours after
      injury, both crude and purified curcumin reduce the percentage of unburned
      interspaces that undergo necrosis in a rat hot comb burn model. The effects of
      purified curcumin appear to be bimodal, suggesting more than one mechanism of
      action. The effects of curcumin do not appear to be mediated by iron chelation.

PMID- 21088616
TI  - Use of dexmedetomidine for sedation in critically ill mechanically ventilated
      pediatric burn patients.
AB  - Dexmedetomidine has previously been used only for short-term, procedural sedation
      in children. The purpose of this review was to describe the dosing, safety, and
      efficacy of dexmedetomidine for sustained sedation in intubated pediatric burn
      patients. The authors reviewed acutely burned children treated between 2005 and
      2008 who were intubated during their course of care and who received
      dexmedetomidine for sedation. Patients served as their own controls using the
      time periods when they received sedatives other than dexmedetomidine. Eleven
      patients with 17 dexmedetomidine treatment courses were identified. The median
      patient age was 7 years (range 1.6-17 years), and median burn size was 30.5% TBSA
      (range 6-59%). Patients were ventilated for a median of 9 days (range 4-46 days).
      The median initial dose of dexmedetomidine was 0.39 MUg/kg/hr (range 0.10-1.16
      MUg/kg/hr), with a median infusion dose of 0.57 MUg/kg/hr (range 0.11-1.17
      MUg/kg/hr) and median treatment duration of 40 hours (range 1-356 hours). None of
      the patients received dexmedetomidine loading dose. Patients achieved more
      appropriate Riker scores while treated with dexmedetomidine than while being
      treated with other sedatives (3.8 vs 3.3, P = .003). The incidence of hypotension
      and/or bradycardia while on dexmedetomidine was not greater than when it was not
      being used. Clinically significant rebound hypertension and tachycardia were
      absent on discontinuation of dexmedetomidine. No unplanned extubations were
      observed. Median length of hospital stay was 49 days (range 7-118 days).
      Dexmedetomidine seems to be safe and effective for sedation of pediatric burn
      patients on mechanical ventilation with close cardiovascular monitoring.

PMID- 21088617
TI  - Red blood cell morphology reporting: how much is a waste of time?
AB  - Red blood cell morphology (RBC-M) reporting is a routine requirement for hospital
      laboratories when reporting complete blood counts. However, there is little
      evidence that RBC-M reporting is useful to pediatric clinicians. We surveyed
      pediatric hematology specialists and nonspecialists at the BC Children's Hospital
      (Vancouver, Canada), to evaluate the perceived clinical utility of this
      reporting. Although a large majority of pediatric clinicians refer to RBC-M
      reports in their clinical practice, less than half consider these reports to be
      clinically useful. Hematology specialists were more likely than nonspecialists to
      identify individual RBC-M descriptions as clinically useful. Some RBC-M
      descriptions, such as anisocytosis, were considered not useful by specialists and
      by nonspecialists. A large proportion of nonspecialist respondents noted that
      they did not know the clinical significance of some of the RBC-M terms.
      Educational initiatives to inform nonspecialists about the clinical significance
      of some RBC-M descriptions should be considered. A few RBC-M descriptions are not
      clinically useful to either specialists or nonspecialists, and these could be
      omitted from RBC-M reports as a step toward improved hematology laboratory
      reporting.

PMID- 21088618
TI  - Human heme oxygenase-1 deficiency presenting with hemolysis, nephritis, and
      asplenia.
AB  - Heme oxygenase-1 (HO-1) is a stress-induced enzyme that catalyses the oxidation
      of heme to biliverdin. The primary deficiency of this enzyme has been shown in HO
      1 knockout mice, and is characterized by intrauterine death and chronic
      inflammation. The first case of human HO-1 deficiency was reported in 1999. Human
      HO-1 deficiency has been observed to involve the endothelial cells more severely,
      resulting in hemolysis and disseminated intravascular coagulation. We report
      another case of human HO-1 deficiency in a young girl with congenital asplenia,
      who presented with severe hemolysis, inflammation, nephritis, which was
      refractory to therapy with corticosteroids, cyclophosphamide, and rituximab.

PMID- 21088619
TI  - Treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV
      HLH); update 2010.
AB  - The clinical features of Epstein-Barr virus-related hemophagocytic
      lymphohistiocytosis (EBV-HLH) vary significantly, from mild to severe, at the
      time of the treatment decision. There are many reports of successful treatments,
      for example conservative treatment without etoposide, HLH-94/2004-type
      immunochemotherapy with etoposide, and hematopoietic stem cell transplantation.
      When considering the treatment of EBV-HLH, the most important factor is the
      finding that a survival benefit is obtained when etoposide-containing therapy is
      initiated within 4 weeks of diagnosis. This indicates that there may be a window
      for observation or conservative corticosteroid/cyclosporine A or intravenous
      immunoglobulin (IVIG) treatment; however, once the disease is defined as "high
      risk" and/or refractory to such therapy, prompt introduction of etoposide
      (ideally within 4 wk) is recommended. In deciding whether the disease is "high
      risk," evaluation of clinical staging, EBV genome copy numbers in the serum,
      cellular EBV tropism, chromosome analysis, and screening for hereditary immuno
      deficient diseases such as familial HLH, are required.

PMID- 21088620
TI  - Cord blood transplantation in children with relapsed or refractory severe
      aplastic anemia.
AB  - Early results of cord blood transplantation (CBT) for severe aplastic anemia were
      poor with a high rate of engraftment failure. We carried out CBT in 5 children
      with relapsed or refractory severe aplastic anemia, using immunosuppressive
      preparative regimens. The median time from the diagnosis to the CBT was 16 months
      (15 to 47 mo), with all the children having failed at least 1 course of
      immunosuppressive therapy. The conditioning regimens consisted of fludarabine,
      cyclophosphamide, and antithymocyte globulin. One patient had an HLA-identical
      sibling donor, and 4 had unrelated donors selected from an NMDP-affiliated cord
      blood bank. Two patients received double-unit grafts to attain a target TNC dose
      of at least 3.0*10/kg. Donor/recipient HLA matching was 6 of 6 (n=2) and 5 of 6
      (n=5). The median nucleated cell dose infused was 5.6 (range, 3.6 to 6.1) *10
      cells/kg. The median infused CD34 dose was 2.9 (range, 1.8 to 7.5) *10 cells/kg.
      All the patients achieved neutrophil engraftment at a median of 13 days (range,
      11 to 25 d). The median time to platelet engraftment was 48 days (range, 34 to 56
      d). After CBT, acute GVHD developed in 4 cases, CMV reactivation in 1, pneumonia
      in 1, and sepsis in 1. Four patients successfully engrafted, but 1 failed to
      engraft and had delayed autologous recovery. However, all patients were now
      transfusion-independent at the time of reporting. This result suggests that CBT
      using optimal conditioning regimens can be a salvage treatment for patients
      without a suitable bone marrow donor and warrants further prospective studies.

PMID- 21088621
TI  - Massive hemoperitoneum with splenic infarction in Evans syndrome.
AB  - Evans syndrome is a very rare hematologic autoimmune disease, characterized by a
      direct Coombs' positive hemolytic anemia and immune thrombocytopenic purpura
      without a known underlying etiology. The clinical course is generally chronic
      with frequent relapses and remissions. Evans syndrome usually is complicated by
      hemolytic or thrombocytopenic symptoms. This is seldom associated with thrombosis
      or infarction. Reported here is a case with massive hemoperitoneum because of
      splenic infarction with rupture, in an 18-month-old male patient with Evans
      syndrome, and the embolization of splenic artery. This article also carries
      clinical and imaging features and the review of medical literature.

PMID- 21088622
TI  - Recurrent hemarthrosis in a boy with synovial hemangioma: a case report.
AB  - We describe an unusual case of hemarthrosis caused by a synovial hemangioma in an
      11-year-old boy. The initial presentations were sudden onset of spontaneous knee
      swelling and painful sensation accompanied by limitation of joint movement. The
      patient had a history of recurrent swelling with spontaneous remission over the
      same location in the past year. In addition, diffuse cutaneous hemangioma since
      infancy was also noted. Synovial involvement of a cutaneous hemangioma was
      confirmed by multidetector computed tomography and arthroscopy. The patient was
      started on oral corticosteroid and beta-blocker. No recurrence was noted on
      multidetector computed tomographic images or clinical examination at the 2-month
      follow-up.

PMID- 21088623
TI  - Surgical treatment of scoliosis associated with Marfan syndrome by using
      posterior-only instrumentation.
AB  - Surgical treatment of scoliosis associated with Marfan syndrome poses a challenge
      to spine surgeons. This retrospective study was undertaken to determine whether
      posterior-only surgery with instrumented fixation and fusion addresses the
      correction of scoliosis and maintains curve correction. Twelve consecutive
      patients with Marfan syndrome were treated between 2002 and 2007 for scoliosis by
      posterior segmental instrumentation using pedicle screws or hybrid thoracic-hook
      and lumbar-screw constructs. Their preoperative Cobb angle averaged 66 +/- 10
      degrees  (range: 55-90 degrees ). The average operation time was 252 +/- 36 min
      (range: 200-300 min) and the average blood loss was 690 +/- 117 ml (range: 550
      920 ml). No significant complications were found. All the patients were followed
      for a minimum of 2 years (range: 2.4-6.8 years). The average Cobb angle was
      corrected to 23 +/- 8 degrees  (range: 13-35 degrees ) immediately after surgery
      and 28 +/- 9 degrees  (range: 14-43 degrees ) with a correction rate of 58 +/-
      13% at final follow-up. The results indicate that posterior-only surgery with
      instrumented fixation and fusion is effective and safe for the treatment of
      scoliosis in selected patients with Marfan syndrome.

PMID- 21088624
TI  - Achondroplasia in female twins: surgical indications.
AB  - Although in literature achondroplasia has been described profusely, reports on
      achondroplastic twins are limited. We present two cases of monozygotic female
      twins with achondroplasia, who underwent limb-lengthening surgical procedure with
      external fixation in the following five steps: tibia, femur, tibia; femur, homer.
      Both the cases presented a good limb length and an optimal correction of
      associated deformities after the treatment, fulfilling the indications. Surgical
      indications were mostly led by the axial deviations of the lower limbs, and the
      timing of the limb-lengthening procedures has been the same in both couples
      showing the importance of this aspect.

PMID- 21088625
TI  - Psychophysiological responses to self-paced treadmill and overground exercise.
AB  - Speculation exists that a positive affective response experienced during exercise
      may play an important role in predicting exercise adherence. Previous studies
      using self-paced exercise protocols have been associated with health benefits and
      pleasant experiences. However, all of these studies were conducted in
      laboratories, and consequently, the external validity of the findings may be
      questionable. PURPOSE: To determine whether environmental settings (treadmill vs
      overground) differentially influence physiological, perceptual, and affective
      responses to exercise at a self-selected pace. METHODS: Thirty-four individuals
      (17 men and 17 women) between 18 and 30 yr volunteered to participate in this
      study. During the orientation session, individuals underwent an initial
      screening, anthropometric measurements, and familiarization with the experimental
      procedures. Next, subjects underwent a maximal treadmill test. In the two
      experimental trials, participants performed 20-min bouts of treadmill and
      overground walking at a self-selected pace, which were completed in a
      counterbalanced order. At least 48 h separated experimental trials. RESULTS:
      Using repeated-measures ANOVA, overground walking speed was significantly faster
      than treadmill walking speed (P < 0.01) during the 20-min bout of self-paced
      exercise. However, exercise intensity (%VO2R and %HRR) and perceived exertion
      during the session of overground walking were significantly lower (P < 0.05) when
      compared with those during the treadmill session. In addition, affective valence
      was more positive during the session of overground walking than during the
      treadmill session (P < 0.01). CONCLUSIONS: These data extend previous findings by
      showing that environmental setting influences physiological, perceptual, and
      affective responses during exercise at a self-selected pace. Self-paced exercise
      performed over ground resulted in lower perceptual and more positive affective
      responses.

PMID- 21088626
TI  - Limitations of salivary osmolality as a marker of hydration status.
AB  - Salivary osmolality (Sosm) is a potentially useful hydration marker but may be
      confounded by oral artifacts. PURPOSE: This study aimed to determine the efficacy
      of Sosm for detecting hypohydration and evaluate the effect of a simple mouth
      rinse. METHODS: Eight healthy volunteers (six males and two females; age = 22 +/-
      7 yr, body mass = 83.7 +/- 14.9 kg, height = 176.9 +/- 9.2 cm) were measured for
      nude body mass (BM), plasma osmolality (Posm), and Sosm when euhydrated (EUH) and
      again when hypohydrated (HYP) by exercise-heat exposure with fluid restriction.
      After the initial saliva sample during HYP, a 10-s mouth rinse with 50 mL of
      water was provided, and saliva samples were obtained 1 min (RIN01), 15 min
      (RIN15), and 30 min (RIN30) after rinse. The ability of Sosm to detect HYP was
      compared with Posm. RESULTS: Volunteers were hypohydrated by -4.0% +/- 1.2% of BM
      (range = -2.2% to -5.3%). Sosm was elevated above EUH after hypohydration (EUH 58
      +/- 8 mmol . kg vs HYP 96 +/- 28 mmol . kg, P < 0.05). Sosm baseline and change
      values displayed more variability than Posm based on ANOVA and regression
      analyses. After the oral rinse, saliva decreased in concentration (RIN01 = 61 +/-
      17 mmol . kg, P < 0.05) but returned to prerinse values within 15 min (RIN15 =
      101 +/- 25 mmol . kg) and remained similar 30 min after (RIN30 = 103 +/- 33 mmol
      . kg). CONCLUSIONS: Sosm was remarkably altered 1 min after a brief water mouth
      rinse. Fifteen minutes proved an adequate recovery time, indicating that the
      timing of oral artifacts and saliva sample collection is critical when
      considering Sosm for hydration assessment. Given the inherent variability and
      profound effect of oral intake, use of Sosm as a marker of hydration status is
      dubious.

PMID- 21088627
TI  - Delayed-onset muscle soreness alters the response to postural perturbations.
AB  - INTRODUCTION: Eccentric contractions induce muscle fiber damage that is
      associated with delayed-onset muscle soreness and an impaired ability of the
      muscle to generate voluntary force. Pain and pathophysiological changes within
      the damaged muscle can delay or inhibit neuromuscular responses at the injured
      site, which is expected to have an effect on reflex activity of the muscle.
      PURPOSE: The aim of the study was to investigate the reflex activity of knee
      muscles to rapid destabilizing perturbations, before, immediately after, and 24
      and 48 h after eccentric exercise. METHODS: Bipolar surface EMG signals were
      recorded from 10 healthy men with seven pairs of electrodes located on the knee
      extensor muscles (vastus medialis, rectus femoris, and vastus lateralis) and knee
      flexor muscles (the medial and lateral heads of the hamstring and the medial and
      lateral heads of gastrocnemius) of the right leg during rapid perturbations.
      RESULTS: The maximal voluntary contraction force decreased by 24% +/- 4.9%
      immediately after exercise and remained reduced by 21.4% +/- 4.1% at 24 h and by
      21.6% +/- 9.9% at 48 h after exercise with respect to baseline. During the
      postexercise postural perturbations, the EMG average rectified value of the knee
      extensor muscles was significantly lower than baseline (P < 0.001). Moreover, the
      decrease in average rectified value over time during postexercise sustained
      contractions was greatest compared with the session before exercise (P < 0.0001).
      CONCLUSIONS: Reflex activity in leg muscles elicited by rapid destabilizing
      perturbations is reduced after exercise-induced muscle soreness.

PMID- 21088628
TI  - Validation of the GENEA Accelerometer.
AB  - PURPOSE: The study aims were: 1) to assess the technical reliability and validity
      of the GENEA using a mechanical shaker; 2) to perform a GENEA value calibration
      to develop thresholds for sedentary and light-, moderate-, and vigorous-intensity
      physical activity; and 3) to compare the intensity classification of the GENEA
      with two widely used accelerometers. METHODS: A total of 47 GENEA accelerometers
      were attached to a shaker and vertically accelerated, generating 15 conditions of
      varying acceleration and/or frequency. Reliability was calculated using SD and
      intrainstrument and interinstrument coefficients of variation, whereas validity
      was assessed using Pearson correlation with the shaker acceleration as the
      criterion. Next, 60 adults wore a GENEA on each wrist and on the waist (alongside
      an ActiGraph and RT3 accelerometer) while completing 10-12 activity tasks. A
      portable metabolic gas analyzer provided the criterion measure of physical
      activity. Analyses involved the use of Pearson correlations to establish
      criterion and concurrent validity and receiver operating characteristic curves to
      establish intensity cut points. RESULTS: The GENEA demonstrated excellent
      technical reliability (CVintra = 1.4%, CVinter = 2.1%) and validity (r = 0.98, P
      < 0.001) using the mechanical shaker. The GENEA demonstrated excellent criterion
      validity using VO2 as the criterion (left wrist, r = 0.86; right wrist, r = 0.83;
      waist, r = 0.87), on par with the waist-worn ActiGraph and RT3. The GENEA
      demonstrated excellent concurrent validity compared with the ActiGraph (r = 0.92)
      and the RT3 (r = 0.97). The waist-worn GENEA had the greatest classification
      accuracy (area under the receiver operating characteristic curve (AUC) = 0.95),
      followed by the left (AUC = 0.93) and then the right wrist (AUC = 0.90). The
      accuracy of the waist-worn GENEA was virtually identical with that of the
      ActiGraph (AUC = 0.94) and RT3 (AUC = 0.95). CONCLUSION: The GENEA is a reliable
      and valid measurement tool capable of classifying the intensity of physical
      activity in adults.

PMID- 21088629
TI  - Congenital cranio-orbital myofibroma.
AB  - A 1-day-old female newborn presenting with a severe left proptosis was found, on
      imaging, to have a cranial mass extending in both orbits and ethmoid sinuses.
      Tumor debulking and biopsy were performed through a lateral orbitotomy. Based on
      histologic findings, a diagnosis of infantile myofibroma was made. No involvement
      was found in other areas of the body. The patient died because of respiratory
      arrest after intracranial surgery that was performed 45 days after the orbital
      surgery. To the authors' knowledge, only one similar case of cranio-orbital
      myofibroma has been reported previously. This tumor should be considered in the
      differential diagnosis of congenital proptosis and cranio-orbital tumor. In such
      cases, tumor debulking can be performed through orbitotomy.

PMID- 21088630
TI  - Re: "management of facial disfigurement in orbitotemporal neurofibromatosis".

PMID- 21088631
TI  - Tarsal elastic fiber distribution: an anatomic study.
AB  - PURPOSE: To analyze the distribution of tarsal elastic fibers, with special
      emphasis on the meibomian duct area. METHODS: Nine postmortem orbits (5 right, 4
      left) of 7 Asian cadavers (mean age at death: 82 years, age range: 73-94 years),
      fixed in 10% buffered formalin, were used. Full-thickness sagittal sections of
      the upper eyelid specimens were dehydrated and embedded in paraffin and cut in 7
      MUm-thick sagittal sections. Sliced sections were stained with elastica van
      Gieson. RESULTS: Elastic fibers were demonstrated in all tarsal plates. They were
      mostly distributed around the meibomian ducts and much less around the acini or
      in the tarsal stroma. These elastic fibers were also seen in the area of the
      muscle of Riolan. The outer part of the meibomian acini was less surrounded by
      elastic fibers. CONCLUSIONS: Tarsal elastic fibers are distributed mainly around
      the meibomian ducts, and much less around the acini or in the tarsal stroma. The
      fibers were also shown to extend to the area of the muscle of Riolan. These
      anatomical findings may help clarify the mechanisms involved in meibomian
      secretion.

PMID- 21088632
TI  - Primitive neuroectodermal tumor of the orbit in adults: a case series.
AB  - PURPOSE: To present the clinical, radiologic, and histopathologic features of
      orbital primitive neuroectodermal tumor (PNET) in 5 adult patients. METHODS:
      Retrospective case series of 5 adult patients with orbital PNET. Orbitotomy was
      performed in all cases. The authors report clinical findings, radiologic
      features, histopathology, immunohistochemical analysis, management, and outcomes
      for 5 patients with orbital PNET. RESULTS: Five adult patients presented with
      progressive unilateral proptosis and visual impairment. Common radiographic
      findings included a heterogeneous mass without associated destructive features,
      located in the superior and/or lateral orbit. Four cases demonstrated strong
      immunohistochemical staining for CD99 in a membranous pattern. One case required
      chromosomal analysis with fluorescence in situ hybridization to confirm the
      diagnosis. All patients received chemotherapy and/or orbital radiation with
      resolution of proptosis but no improvement of vision. One patient died of
      disease. CONCLUSIONS: To the authors' knowledge, this is the largest series of
      orbital PNET in adults. This tumor has an age demographic wider than previously
      believed and should be considered in the differential diagnosis of a
      hypercellular small round cell orbital tumor in both children and adults. Current
      treatment regimens are not standardized but typically use a similar approach to
      the treatment of Ewing sarcoma. Orbital PNET appears to have less propensity for
      metastasis compared with PNET in other locations. However, long-term
      aggressiveness remains to be proven.

PMID- 21088633
TI  - Off-road vehicle trauma in children: a New South Wales perspective.
AB  - OBJECTIVE: There is paucity of data on off-road vehicle injuries in children in
      Australia. We performed a retrospective study from 1998 to 2003 to analyze the
      frequency and nature of injuries in children involved in off-road vehicle crashes
      in the state of New South Wales. METHODS: Medical records were identified from
      search of the trauma database and hospital medical records database for off-road
      (all-terrain) vehicles. RESULTS: A total of 271 children were identified, 86% of
      whom were boys. The mean age was 10 years (range, 2-16 years); and the mean
      length of stay, 5.8 (9) days (range, 1-40 days). The mean injury severity score
      was 6 (5.9). Most were drivers (85%). Injury mechanism was falls in 161;
      collision with stationary object, 54; moving object, 4; rollovers, 7; and others,
      8. Eighty-four percent were on 2 wheelers, whereas 11% were quad bikes, and the
      rest were on tricycles or other vehicles. Distribution of the body region injured
      was head and neck in 66 patients; face, 51; chest, 25; abdomen, 36; pelvis, 5;
      spines, 14; upper limbs, 96; and lower limbs, 116. Only 55% were helmeted at the
      time of the incident. Sixty-five percent of these children required surgical
      treatment. Most were fractures (98) followed by soft tissue injuries (49).
      Seventeen had posthead injury sequelae requiring rehabilitation support, and 21
      required multiple surgeries. There were 7 deaths during the study period in New
      South Wales. CONCLUSIONS: Off-road motor vehicle injuries are a significant
      problem in children. There are no legal safety regulations for use of these
      vehicles. With the increasing sales of these vehicles, the incidence of injury
      may rise. There seems a need for education and legislation in relation to the
      safety issues concerned with these vehicles.

PMID- 21088634
TI  - Characteristics of falls and risk of injury in children younger than 2 years.
AB  - INTRODUCTION: Although many studies have shown that short falls by children
      rarely result in serious injury, no recent study in the United States has
      assessed the prevalence and the characteristics of such falls. Because the
      history of a short fall often is given in the instance of suspected child abuse,
      data addressing the characteristics, the frequency, and the severity of such
      falls would assist in abuse investigations. METHODS: Anonymous questionnaires
      were distributed at primary care offices to parents of children younger than 5
      years. Parents answered a series of questions regarding any falls their children
      had sustained before the age of 2 years. Information gathered included the age of
      the child at the time of the fall, the details about the fall, the medical
      attention sought, and any injuries sustained. RESULTS: We received a total of 307
      eligible surveys. There were 209 falls reported for 122 children. Only 24% of
      those children sustained any injury as a result of the fall. Most (85%) of the
      children who sustained injuries had a bruise or a bump. Of the 20% (40 children)
      who were brought for medical care, only 13 children received medical treatment.
      The most severe injuries were in 2 children who sustained concussions; only 4
      children had permanent injury (cutaneous scars). Children who fell on a hard
      surface were 6 times more likely to have an injury compared with children who
      fell on a soft surface (P = 0.001) In addition, for every 1 unit increase in fall
      height, risk of injury increased by a factor of 2.3. CONCLUSIONS: In short falls,
      ground surface and fall height were significant predictors of injury risk. The
      results of this study also support the opinion that short falls rarely cause
      injury. Therefore, a history of a short fall in a seriously injured child should
      raise the suspicion of child abuse.

PMID- 21088635
TI  - Barriers to discharge from a 24-hour observation unit for children with
      bronchiolitis.
AB  - OBJECTIVES: The aim of this study was to determine physician-identified barriers
      to discharge of patients with bronchiolitis from a 24-hour emergency department
      based observation unit. METHODS: Patients 3 to 24 months of age with a diagnosis
      of bronchiolitis were prospectively enrolled from January through April 2008.
      Patients were treated according to a standard hospital-wide bronchiolitis pathway
      that included an option for discharge on home oxygen. Treating physicians
      recorded barriers to discharge in those not sent home within 24 hours. The
      primary outcome was successful discharge within 24 hours; we analyzed barriers to
      such discharges. RESULTS: Fifty-five patients were enrolled in the study.
      Discharge within 24 hours failed in 30 patients (55%; 95% confidence interval
      [CI], 42%-67%). Among the 25 discharged patients, 6 (24%) went home on
      supplemental oxygen without adverse outcomes or readmission. Hypoxia was the most
      commonly identified barrier to discharge (n = 22, 73%). Of the 22 cases where
      hypoxia was a barrier, 18 (82%) also noted the need for deep nasal suctioning; 12
      (55%), parental discomfort; 12 (55%), respiratory distress; 10 (46%), poor
      feeding; and 4 (18%), MD discomfort. CONCLUSIONS: Hypoxia was the most common
      barrier to discharge within 24 hours for patients with bronchiolitis, and a
      common cofactor when other barriers were identified. Research on home oxygen, the
      use of deep nasal suctioning, and parental discomfort with early discharge may be
      useful in reducing the need for inpatient care for bronchiolitis.

PMID- 21088636
TI  - Physician practice variation in the pediatric emergency department and its impact
      on resource use and quality of care.
AB  - OBJECTIVE: To evaluate variation in case-mix adjusted resource use among
      pediatric emergency department (ED) physicians and its correlation with ED length
      of stay (LOS) and return rates. METHODS: Resource use patterns at 2 EDs for 36
      academic physicians (163,669 patients at ED1) and 45 private physicians (289,199
      patients at ED2) from 2003 to 2006 were abstracted for common laboratory tests,
      imaging studies, intravenous therapy (fluids/antibiotics), LOS and 72-hour return
      rate for discharged patients, and hospital admissions for all patients. Case-mix
      adjustment was based on triage acuity, diagnostic category, demographics, and
      temporal measures. OUTCOME MEASURES: (1) adjusted overall resource use for ED1
      and ED2 physicians and (2) observed-to-expected ratios for ED1 physicians.
      RESULTS: Case-mix adjusted hospital admission rates among physicians varied
      nearly 3-fold (6.3%-18%) for ED1 and 8-fold (2.5%-19.4%) for ED2. Intravenous
      therapy use varied 2-fold (4.9%-10.4%) at ED1 and 3-fold (3.6%-11.4%) at ED2.
      Emergency department 2 physicians had an almost 2-fold (10.9%-20.6%) variation in
      imaging use. Variation in head computed tomography use was 2-fold (1.1%-2.5%) at
      ED1 and 5-fold (0.9%-4.8%) at ED2. Physicians had longer than expected LOS if
      they had higher than expected use of laboratory tests (r, 0.41; 95% confidence
      interval [CI], 0.09-0.65; P < 0.05) and imaging (r, 0.48; 95% CI, 0.17-0.69; P <
      0.01). Return rate was not significantly correlated with resource use in any
      category. Physicians with higher than expected use of laboratory tests had higher
      than expected use of imaging (r, 0.62; 95% CI, 0.36-0.78; P < 0.001), head
      computed tomography (r, 0.49; 95% CI, 0.19-0.70; P < 0.01), and intravenous
      therapy (r, 0.51; 95% CI, 0.20-0.71; P < 0.01). CONCLUSIONS: Significant
      variation exists in physician use of common ED resources. Higher resource use was
      associated with increased LOS but did not reduce return to ED. Practice variation
      such as this may represent an opportunity to improve health care quality and
      decrease costs.

PMID- 21088637
TI  - Adherence to guidelines for managing the well-appearing febrile infant:
      assessment using a case-based, interactive survey.
AB  - OBJECTIVES: The objectives of the study were (1) to determine the relative use of
      strategies for managing the well-appearing febrile infant and (2) to determine
      clinician adherence to protocol recommendations. METHODS: Members of the American
      Academy of Pediatrics Section on Emergency Medicine were asked to complete an
      online, interactive, case-based questionnaire. Infants with a temperature of 38.6
      degrees C who were otherwise completely well were presented. Respondents ordered
      laboratory studies and received results. Treatment and disposition decisions
      based on those results were queried. Clinicians reported which published set of
      guidelines they followed. Major discriminating features of guidelines were used
      to assess adherence. RESULTS: Two hundred ninety-nine (30%) clinicians completed
      the survey. The relative use of the 3 main guidelines was as follows:
      Philadelphia, 20%; Rochester, 15%; and Boston, 13%. Of respondents reporting that
      their practice is based on the Rochester criteria, 98% performed a lumbar
      puncture, 86% administered antibiotics, and 93% admitted the 25-day-old infant to
      the hospital, despite recommendations that a lumbar puncture was unnecessary and
      that the infant be managed as an outpatient without antibiotics. Similar
      deviations were seen among respondents who reported using the other criteria.Many
      respondents treated the infants with antibiotics, without obtaining cerebrospinal
      fluid for culture, despite recommendations against this practice. CONCLUSIONS:
      Although most physicians report following published guidelines for the management
      of the well-appearing febrile infant, compliance with recommendations is poor.
      The effect that deviating from the guidelines has on patient outcome is unknown.
      Despite recommendations to the contrary, many physicians administer antibiotics
      without obtaining cerebrospinal fluid for culture.

PMID- 21088638
TI  - Hyperammonemia in the pediatric emergency care setting.
AB  - Hyperammonemia is encountered frequently in acutely ill children presenting for
      emergency care with altered levels of consciousness (ALOC). Ammonia production,
      metabolism, and excretion are affected by different variables. Hyperammonemia may
      be a transient state or may signify more grave etiologies as inborn errors of
      metabolism. Levels of ammonia are also affected by proper sampling technique,
      transport, and analysis. OBJECTIVES: To determine the level of ammonia in acutely
      ill children with ALOC, identify causes of hyperammonemia, and correlate levels
      with illness severity and morbidity. DESIGN: Observational study. SETTING:
      Emergency department at Cairo University Specialized Paediatric Hospital.
      METHODS: Fifty cases of acutely ill pediatric patients with ALOC who presented to
      the emergency department were included in the study from 2008 through 2009.
      Emergency department patients (n = 20) with known diseases that may induce
      hyperammonemia were excluded. Patients were subjected to detailed history taking
      with emphasis on factors affecting ammonia levels and thorough clinical
      examination. A cohort group of age- and sex-matched children acted as a control
      group. RESULTS: The measured blood ammonia level ranged between 13 and 265
      MUmol/L, with a mean level of 95 MUmol/L. Sixty percent of the children with ALOC
      had ammonia levels of greater than 75 MUmol/L, with levels greater than 200
      MUmol/L seen in 6% of the studied sample. The study demonstrated a highly
      significant statistical difference between children with ALOC and control
      groups.There was no correlation between blood ammonia level and age. Correlations
      of ammonia levels were also conducted in comparison with etiological diagnoses
      and laboratory parameters with no statistical significance.There was no
      statistical significance between ammonia level and duration of illness,
      Sequential Organ Failure Assessment score, or Glasgow Coma Scale score/Morray
      Scale score. CONCLUSIONS: Clinicians should consider testing children with ALOC
      for hyperammonemia, provided that a clear understanding of its metabolism and
      factors controlling it are understood. Proper sampling must be ensured. Mild
      elevations of ammonia levels are fairly common, but exceedingly high levels
      should raise concern and may require further evaluation.

PMID- 21088639
TI  - An emergency department intervention to improve knowledge of child passenger
      safety.
AB  - OBJECTIVES: The objective of the study was to test the impact of an educational
      video in improving child passenger safety knowledge. METHODS: This was a
      prospective randomized study performed in the emergency department of an urban
      children's hospital involving parents of non-critically ill children younger than
      9 years. Parents were randomized to observe a video on child passenger safety or
      comparison group. All completed a survey, 8-question pretest at enrollment, and
      posttest after 1 month and received written safety materials at discharge. The
      outcome measure to test knowledge was the difference in mean pretest-posttest
      scores on a questionnaire. RESULTS: We enrolled 274 parents (137 intervention,
      137 comparison). Thirty subjects were found ineligible for analysis after
      enrollment because their children were outside the age range for inclusion.
      Analysis was restricted to 131 parents in the intervention group and 113 in the
      comparison group. No significant differences existed between groups when
      comparing demographics and child passenger safety characteristics except for the
      number of children in the household. After excluding those lost to follow-up (91
      parents) and who dropped out (14 parents), analysis was restricted to 74 subjects
      in the intervention group and 65 in the comparison group. Mean pretest scores
      were as follows: intervention, 4.95 (SD, 1.49); comparison, 5.12 (SD, 1.32). Mean
      posttest scores were as follows: intervention, 5.24 (SD,1.60); comparison, 4.77
      (SD, 1.39). Difference in mean pretest-posttest scores showed a significant
      improvement in the intervention group compared with the comparison group: 0.65
      (95% confidence interval, 0.14-1.16) on independent-samples t test (P = 0.012).
      CONCLUSIONS: Child passenger safety education can be effectively imparted to
      parents in the emergency department.

PMID- 21088640
TI  - Patient-reported outcome measures in plastic surgery: use and interpretation in
      evidence-based medicine.
AB  - Understanding patients' perceptions of surgical results and their impacts on
      quality of life is of primary importance in plastic surgery, as procedures are
      largely performed to improve either appearance or function. Patient-reported
      outcome measures are questionnaires specifically designed to quantify aspects of
      health-related quality of life from the patient's perspective. This article
      presents an overview of patient-reported outcome measures. It also aims to
      provide plastic surgeons with the necessary critical appraisal skills to
      interpret and apply evidence from patient-reported outcomes research in their own
      clinical practice.

PMID- 21088641
TI  - Free tissue transfers for limb salvage in patients with end-stage renal disease
      on dialysis.
AB  - BACKGROUND: Microvascular surgery plays a major role in the reconstructive
      process of limb salvage. However, microsurgery in the patient with renal disease
      is still considered a high-risk procedure. Some authors have even recommended
      immediate amputation because of poor long-term survival in patients with renal
      failure and lower limb ischemia. METHODS: A retrospective review of all patients
      with end-stage renal disease on hemodialysis who underwent free flap surgery at
      Dalin Tzu Chi General Hospital was included in the study. Data were collected
      over a 5-year period, between June of 2005 and June of 2009. RESULTS: A total of
      20 patients were included in the study, of which 11 were men and nine were women.
      The average age of the patients was 63 years. All had a history of diabetes
      mellitus with peripheral vascular disease. Seven of the 20 patients had undergone
      prior vascular intervention. The total flap survival rate was 95 percent. Four
      patients eventually required major limb amputation because of progressive
      infection at the recipient site. There were no further major limb amputations in
      these patients during the long-term follow-up. The total limb salvage rate was 80
      percent. The average follow-up was 30 months. CONCLUSIONS: The authors' present
      approach shows that the results of limb salvage in this particular group of
      patients are not as discouraging as previously reported. In the description of
      patients with renal disease, the authors suggest that they not be described as
      one entity but that they be divided into subgroups so that this better reflects
      the risk of surgery and the success of limb salvage.

PMID- 21088643
TI  - Is presurgical nasoalveolar molding therapy more effective in unilateral or
      bilateral cleft lip-cleft palate patients?
AB  - BACKGROUND: The purpose of this study was to compare the efficacy of presurgical
      nasoalveolar molding in treating unilateral versus bilateral cleft lip-cleft
      palate patients. METHODS: A blinded, retrospective study was conducted with 16
      unilateral and 13 bilateral cleft lip-cleft palate patients. Pretreatment and
      posttreatment facial and intraoral impressions were used to compare soft- and
      hard-tissue changes. RESULTS: Nasoalveolar molding therapy improves nasal angle
      in unilateral (p = 0.010) and bilateral cleft lip-cleft palate (p = 0.001)
      patients, and improves nostril width in unilateral (p = 0.005) and bilateral
      cleft lip-cleft palate (p = 0.028) patients. Treatment significantly improves
      nostril breadth only in unilateral cleft lip-cleft palate patients (p = 0.005).
      Compared with bilateral cleft lip-cleft palate patients, unilaterally affected
      patients were more asymmetric before and after nasoalveolar molding therapy.
      Nasoalveolar molding more effectively increases columellar height (p = 0.002) and
      columellar width (p = 0.002) in the bilateral cleft lip-cleft palate group.
      Although starting bialar widths did not significantly differ between the two
      groups, nasoalveolar molding significantly decreased bialar width only in
      unilateral cleft lip-cleft palate patients (p = 0.032). When the intersegment
      alveolar cleft distances of the bilateral cleft lip-cleft palate patients were
      summed, an improvement similar to that in unilateral cleft lip-cleft palate
      patients was observed. Furthermore, nasoalveolar molding appeared to prevent
      alveolar width widening as patients continued to grow. CONCLUSIONS: There are
      differences in efficacy between unilateral and bilateral cleft lip-cleft palate
      patients undergoing nasoalveolar molding. Understanding these differences may
      help physicians and dentists better shape expectations.

PMID- 21088644
TI  - Use of vascularized free fibular head grafts for upper limb oncologic
      reconstruction.
AB  - BACKGROUND: Transfer of a vascularized fibular graft is the method of first
      choice for reconstruction of defects of long bones. In particular, the
      vascularized fibula head graft is preferred for patients with bone defects of the
      upper limb involving the distal radius or the proximal humerus. The aim of the
      present study was to analyze the operative results, complications, and
      postoperative function after vascularized fibula head graft transfer and the
      indications for this procedure. METHODS: From 1998 through 2008, vascularized
      fibula head graft transfer was performed in eight patients to reconstruct bone
      defects following resection of tumors of the upper limb. The primary site of the
      tumor was the proximal humerus in four patients and the distal radius in four
      patients. The postoperative course of the transferred bone was examined, and
      functional results were evaluated. RESULTS: All vascularized fibula head grafts
      were transferred successfully. During the follow-up period, absorption of the
      transferred fibula head was not observed. The mean overall functional rating of
      the reconstructed shoulder joint was 70 percent. The range of motion of the
      reconstructed wrist joint showed no specific patterns, and instability of the
      wrist joint was observed in only one case. CONCLUSIONS: The authors believe that
      the vascularized fibula head graft transfer is a safe and reliable method for
      reconstructing the upper limb, especially for patients with a defect of the
      distal radius or the proximal humerus. This procedure is also useful for
      pediatric patients, in whom bone growth is expected after transplantation, and
      for salvage procedures after reconstructive materials of an artificial joint have
      failed.

PMID- 21088645
TI  - Anterior chest wall reconstruction with a low skin paddle pedicled latissimus
      dorsi flap: a novel flap design.

PMID- 21088646
TI  - Significant differences in skin irritation by common suture materials assessed by
      a comparative computerized objective method.
AB  - BACKGROUND: Erythema can be described only through subjective evaluation, except
      when it is quantified by digital image analysis software. Using such software,
      the authors performed comparisons of the erythema produced after skin closure of
      clean surgical wounds. Five suture materials were compared with respect to the
      local skin irritation that was caused. Different quantities of erythema are
      produced by suture material after the skin closure of clean surgical wounds. The
      authors present an objective method of measuring how unreactive a suture material
      is in comparison with another when applied to the skin. METHODS: The suture
      materials polydioxanone, polypropylene blue, polyamide 6, metallic clips, and
      polyglactin were compared in the present study. Digital photographs of 100
      patients were compared by means of software, evaluating red color superiority
      (mean value of red color) in the region surrounding the wound. RESULTS: The least
      to most irritation caused to the skin by different suture materials was
      established for paired data. The Kolmogorov-Smirnov criterion and the Wilcoxon
      signed rank test were used. Polydioxanone was found to have the best performance,
      followed in order by polyglactin, polyamide, polypropylene, and metallic clips.
      Immediately after suture removal, differences between the effects of suture
      materials were statistically significant on postoperative day 10. CONCLUSIONS:
      Absorbable sutures can be used in skin closure of clean surgical wounds and can
      produce less erythematous reaction than nonabsorbable ones. Digital image
      analysis is a reliable method of quantitative evaluation of skin erythema
      resulting after skin closure of surgical wounds.

PMID- 21088647
TI  - Long-term clinical and histological analysis of Integra dermal regeneration
      template.
AB  - BACKGROUND: This study looked at clinical and histological outcomes of patients
      treated with Integra more than 2 years earlier. Although previous studies have
      investigated the short-term clinical and histological results, there have been no
      studies to investigate longer-term changes. METHODS: Fourteen patients (23 sites)
      were assessed. Patients used a visual analogue scale to score characteristics of
      their scars. Objective evaluation of the reconstructions was carried out using
      the Cutometer MPA580. Punch biopsy specimens of the sites were stained and
      labeled immunohistochemically with S100, CD31, and CD34 antisera. RESULTS: The
      highest scoring category by patients was softness (median, +45 percent). The
      lowest score was sweating, which all patients scored 0. The median Cutometer
      readings ranged from 39 to 52 percent of the control values. Histological
      examination showed three patterns of collagen arrangement; parallel arrangement
      was found in over 60 percent of specimens. Elastic fibers were identified in all
      specimens; however, all were of abnormal morphology. The majority of specimens
      showed evidence of nerve fiber regeneration although confined to the mid- or
      lower reticular dermis. There was no regeneration of skin adnexa. CONCLUSIONS:
      This study showed significant improvements in patient-assessed mobility,
      softness, and appearance. Collagen and elastic fibrin were present in all
      specimens, nerve fiber regeneration was limited to the mid- or lower reticular
      dermis, and adnexal structures were absent. The typical wrinkled appearance of
      mature Integra reconstruction cannot be said to be entirely due to a lack of
      elastic fibers.

PMID- 21088648
TI  - Acellular dermal matrix for the treatment and prevention of implant-associated
      breast deformities.
AB  - BACKGROUND: Acellular dermal matrix has been increasingly accepted in prosthetic
      breast reconstruction. Observed benefits include improved control and support of
      implant position, better implant coverage, and the suggestion of a decreased
      capsular contracture rate. Based on this positive experience, it is not
      surprising that acellular dermal matrix would be applied to other challenging
      implant-related problems. This study investigates the use of acellular dermal
      matrix for correction or prevention of implant-associated breast deformities.
      METHODS: Patients who underwent primary aesthetic breast surgery or secondary
      aesthetic or reconstructive breast surgery using acellular dermal matrix and
      implants between November of 2003 and October of 2009 were reviewed
      retrospectively. Patient demographics, indications for acellular dermal matrix,
      and acellular dermal matrix type and inset pattern were identified. Preoperative
      and postoperative photographs, success or failure of the procedure,
      complications, and need for related or unrelated revision surgery were recorded.
      RESULTS: Fifty-two patients had acellular dermal matrix placed alongside 77
      breast prostheses, with a mean follow-up of 8.6 months (range, 0.4 to 30.4
      months). Indications included prevention of implant bottoming-out (n = 6),
      treatment of malposition (n = 32), rippling (n = 20), capsular contracture (n =
      16), and skin flap deficiency (n = 16). Seventy-four breasts (96.1 percent) were
      managed successfully with acellular dermal matrix. Three failures consisted of
      one breast with bottoming-out following treatment of capsular contracture, one
      breast with major infection requiring device explantation, and one breast with
      recurrent rippling. There was a 9.1 percent total complication rate, consisting
      of three mild infections, one major infection necessitating explantation, one
      hematoma, and one seroma. CONCLUSION: Based on this experience in 77 breasts,
      acellular dermal matrix has shown promise in treating and preventing capsular
      contracture, rippling, implant malposition, and soft-tissue thinning.

PMID- 21088649
TI  - Effects of long-term administration of recombinant human protein C in xenografted
      primates.
AB  - BACKGROUND: The role potential of recombinant human activated protein C (rhaPC),
      a recently developed molecule with anticoagulant and antiinflammatory properties,
      in prolonging survival in immunosuppressed primate recipients of porcine renal
      xenografts has been evaluated. METHODS: rhaPC was administered daily for 5 days
      (24 MUg/kg/hr; group A; n = 3) or throughout the postoperative period (8-24
      MUg/kg/hr; group B; n = 2; or 24-48 MUg/kg/hr; group C; n = 4). Animals in group
      D (n = 2) received rhaPC daily (24 MUg/kg/hr) combined with recombinant human
      antithrombin (84 U/kg every 8 hr). Two animals served as control (group E).
      RESULTS: The results indicate that rhaPC is protective against fibrin deposition
      early after transplantation but does not prevent fibrin deposition and the
      occurrence of acute humoral xenograft rejection (AHXR) later on. Animals in the
      study survived between 8 and 55 days. At the dose used, rhaPC is able to prevent
      fibrin deposition in the graft in the first 2 weeks after xenotransplantation,
      except when it is administered in conjunction with antithrombin. However, rhaPC
      did not prevent the eventual occurrence of AHXR in primate recipients of porcine
      xenografts. CONCLUSIONS: In this pig to primate model, rhaPC confers a short
      advantage in the prevention of early perioperative xenograft damage but does not
      represent an effective strategy for preventing AHXR.

PMID- 21088650
TI  - An integrated safety profile analysis of belatacept in kidney transplant
      recipients.
AB  - BACKGROUND: Belatacept is associated with better renal function and an improved
      cardiovascular/metabolic risk profile versus cyclosporine in kidney transplant
      recipients. The current analysis examined pooled safety data for belatacept
      versus cyclosporine used in combination with basiliximab, mycophenolate mofetil,
      and steroids. METHODS: Patients enrolled in three core studies in de novo kidney
      transplantation were randomized to a more intensive (MI) or less intensive (LI)
      regimen of belatacept or cyclosporine. The pooled analysis included 1425 patients
      (MI: 477; LI: 472; cyclosporine: 476). Median follow-up was approximately 2.4
      years. RESULTS: Belatacept was generally well tolerated. The frequency of deaths
      (MI: 7%; LI: 5%; cyclosporine: 7%) and serious infections (MI: 37%; LI: 32%;
      cyclosporine: 36%) were lower in the LI group versus cyclosporine. The frequency
      of malignancies was 10%, 6%, and 7% in the MI, LI, and cyclosporine groups,
      respectively. Sixteen cases of posttransplant lymphoproliferative disorder (PTLD)
      occurred (n=8 MI; n=6 LI; n=2 cyclosporine), including nine cases involving the
      central nervous system (CNS) (n=6 MI; n=3 LI). The risk of CNS PTLD was highest
      in Epstein-Barr virus(-) recipients; more CNS PTLD cases occurred in the MI
      group. One case of progressive multifocal leukoencephalopathy was reported in the
      MI group. CONCLUSIONS: Treatment with belatacept-based regimens was generally
      safe for a period of at least 2 years. There was a greater risk of PTLD-
      specifically CNS PTLD--in the belatacept groups versus cyclosporine, especially
      in Epstein-Barr virus(-) patients and with the MI dose. The number of deaths and
      serious infections was lower in the LI regimen versus MI and cyclosporine. The
      overall safety profile favored the LI over the MI regimen.

PMID- 21088651
TI  - Method for spontaneous constriction and closure of portocaval shunt using a
      ligamentum teres hepatis in small-for-size graft liver transplantation.
AB  - BACKGROUND: We have developed a new portocaval (PC) shunt creation technique for
      use in small-for-size (SFS) graft liver transplantations. PC shunts are already
      used to avoid SFS graft syndrome in cases of adult-to-adult living donor liver
      transplantation (LDLT), but the current method of creating these shunts is
      subject to two problems: reportal hypertension and liver dysfunction after
      premature ligation of the PC shunt; and graft atrophy and liver dysfunction
      because of the loss of portal venous flow late in the recovery period after LDLT.
      METHODS: Our new technique avoids these two problems simultaneously by using the
      interposed obliterated ligamentum teres hepatis (LTH) to create the PC shunt,
      then obstructing the PC shunt after regeneration of the liver graft. RESULTS: We
      have used this technique in four cases. In all cases, portal venous pressures
      after shunting were lower than those before shunting, and PC shunts with lower
      portal pressure were obstructed faster than that with higher portal pressure.
      CONCLUSION: Our results suggest that the LTH can function as a shape memory graft
      to reduce portal venous flow after regeneration of the graft liver. Using the LTH
      to create a PC shunt might help to prevent both SFS graft syndrome early in the
      recovery period after LDLT and loss of portal venous flow late in the recovery
      period.

PMID- 21088652
TI  - Can adult cardiologists play a role in the prevention of heart disease beginning
      in childhood?

PMID- 21088653
TI  - The benefits of exercise in promoting long and healthy lives - my observations.

PMID- 21088654
TI  - The personal genome and the practice of cardiovascular medicine.
AB  - Recent advances in the DNA sequencing techniques have made it possible to
      sequence the entire protein coding regions of the genome and even the entire
      genome at a reasonable cost. Genetic discoveries, facilitated by these advances,
      have illustrated the enormous genetic diversity of the mankind. Accordingly, the
      genome of each individual has about 4 million sequences that are different from
      the general population, including a significant number of unique sequence
      variants. About 3 million of these variations affect 1 of the 3 billion bases in
      the genome, while the rest affect from 2 to several million base pairs of DNA.
      About 10,000 of these variants in each genome changes the amino acid sequence and
      hence, the protein structure. The biological and clinical significance of these
      DNA sequence variants follow a gradient that ranges from negligible to large. A
      small number of variants impart large effect sizes but those with negligible and
      small effect sizes are quite abundant in the genome. The most important
      contributions of these variants are likely to be in providing insights into the
      molecular mechanisms responsible for diseases, which is essential for the
      ultimate cure of the human disease. These genetic variants also influence
      susceptibility to diseases, responses to treatment and clinical outcome. Variants
      with large effect sizes have the potential to serve as diagnostic markers,
      prognosticators as well as individualization of therapy. The daunting challenge
      in the upcoming years is to identify the variants that have significant clinical
      impacts from those that impose no discernible effects. The landscape of the
      practice of medicine is expected to change with the incorporation of the
      information content of the DNA sequence variants into the routine practice of
      medicine. The medical community needs to be prepared to best utilize the
      information that will be available from "personal genomes" of the patients.

PMID- 21088655
TI  - Where do we currently stand with advice on hormone replacement therapy for women?
AB  - Nearly 250,000 women die each year from cardiovascular disease, making it the
      leading cause of death in women. The initial clinical manifestation of coronary
      artery disease (CAD) in women is usually 10 years later than in men on average,
      with the first myocardial infarction presenting 20 years later. At any age the
      prevalence of CAD is lower in women, but with advancing age, this gender
      differential diminishes. The fact that CAD prevalence is lower in women has led
      to the false presumption that women are protected from cardiovascular diseases.
      Since women live 8 to 10 years longer than men, the absolute number of deaths
      from cardiovascular disease (CVD) exceeds that of men. Although there has been a
      decline in the overall number of cardiovascular deaths, the coronary incidence
      has been increasing in women and decreasing in men. Contrary to belief, CAD
      causes far more deaths in women than does cancer (Figure 1). Consider the
      statistics: approximately 1 out of 3 women will die of a cardiovascular event;
      more than a half-million women die of CVD each year; one women dies of CVD almost
      each minute in the United States; and two-thirds of the women who die suddenly
      have no previously recognized symptoms. Advances in diagnosis and treatment of
      CVD appear to have translated into a survival benefit in men but not in women.
      The mortality due to CVD remains high in women, with no improvement in survival
      trends over time compared to men (Figure 2). This may be related to differences
      and delays in recognizing CVD in women or in treatment strategies, and to
      biological differences. Women with acute coronary syndrome often delay calling
      for professional help and present more frequently with atypical symptoms, such as
      abnormal pain locations, nausea, vomiting, fatigue, and dyspnea. Women not only
      present later from the onset of chest pain but are also sicker at the time of
      diagnosis. Furthermore, there appears to be a bias against heart disease in women
      - both patients and their caregivers/health care providers do not recognize or
      treat CVD in a timely manner in women. Compared to men, women are less likely to
      receive appropriate treatment for heart disease such as optimal control of blood
      pressure, use of aspirin, cholesterol-lowering medications, thrombolytics, or
      referrals for interventions such as balloon/ stent or bypass surgery. Women seem
      to be evaluated less intensively, and referrals for cardiac catheterization are 8
      fold higher in men than in women. The clinical outcomes including myocardial
      infarction mortality, all-cause mortality, and reinfarction rates are worse in
      women with CVD than in men. Many risk factors contribute to CAD in women, but
      menopause is one of the strongest. Risk of CAD in postmenopausal women is 40 to
      50% higher than in premenopausal women, and hormone replacement therapy (HRT)
      increases the risk. This paper discusses the myriad risk factors for CAD in women
      and explores the relationship between CAD and hormone replacement therapy in
      postmenopausal women.

PMID- 21088656
TI  - Coronary heart disease risk stratification: pitfalls and possibilities.
AB  - Atherosclerosis of the coronary arteries, or coronary heart disease (CHD), is the
      most common cause of mortality in U.S. adults. The pathobiology of
      atherosclerosis and its complications is a continuum. At one end of the spectrum
      are young individuals without atherosclerotic disease who have not yet been
      exposed to lifestyle or other risk factors, and at the other end are patients
      with manifest atherosclerosis - myocardial infarction, stroke, and disabling
      peripheral arterial disease - where risk of recurrent disease and death is driven
      by the same factors initially responsible for the emergence of disease. However,
      it is clear that while risk factors are important in the development of CHD, not
      everyone with risk factors develops the disease and not everyone with CHD has
      risk factors. Furthermore, even similar degrees of exposure to a risk factor
      leads to disease in some individuals and not in others. Risk prediction, which is
      crucial in predicting and hence preventing disease, therefore becomes very
      challenging. In this article we review the currently available risk
      stratification tools for predicting CHD risk and discuss potential ways to
      improve risk prediction.

PMID- 21088657
TI  - Management of obesity in the prevention of cardiovascular disease.
AB  - The prevalence of obesity is increasing in the United States and many other
      countries, and has now passed smoking as the most preventable cause of morbidity
      and mortality. Obesity is an excess of adipose tissue that results from a mixture
      of genetic predisposition, environmental influences (e.g., sedentary lifestyle),
      and behavioural components (e.g., food as a reward), and it is a chronic,
      relapsing condition. The rapid increase in obesity prevalence is, however, not
      due to genetic changes but rather is a societal mismatch between physiology and
      environment, where food is abundant and exercise is unnecessary. The definition
      of excess adipose tissue, for the purpose of correlating this to disease
      outcomes, is through body mass index (BMI), which is calculated as weight
      (kg)/height (m2). Overweight is a BMI of 25-29.9 kg/m2, and obesity is a BMI
      equal to or greater than 30 kg/m2. There is evidence that all-cause mortality is
      higher in obese people, primarily due to increased cardiovascular disease (CVD)
      mortality and increased obesity related cancer (colon, breast, uterine, ovarian,
      renal, and pancreatic) mortality.

PMID- 21088658
TI  - Aspirin for primary prevention of cardiovascular disease in women.
AB  - Cardiovascular disease (CVD) accounts for 34% of overall mortality in the United
      States or an average of 1 death every 38 seconds. While the majority of these
      events are related to coronary heart disease (CHD), stroke accounts for a
      sizeable burden of CVD among postmenopausal women. Before 75 years of age, a
      higher proportion of CVD events due to CHD occur in men than in women, as opposed
      to a higher proportion of events due to stroke occurring in women. Sex-based
      disparities in medical care are well documented, and under-treatment of women
      with aspirin for secondary prevention of CVD is a blatant example of the quality
      chasm described in the Institute of Medicine report "between the care we have and
      the care we could have". However, while aspirin appears to be of substantial net
      benefit in secondary prevention, the balance of its beneficial effects and
      bleeding hazards in primary prevention remains less certain, especially in women.
      The current review examines the evidence and provides recommendations for the use
      of aspirin for primary prevention of CVD in women.

PMID- 21088659
TI  - Gigantic coronary sinus associated with concurrent persistent left superior vena
      cava and right ventricular volume overload.
AB  - A 76-year-old women with known atrial fibrillation and congestive heart failure
      presented with increasing shortness of breath. A 2-dimensional (2-D)
      transthoracic echocardiogram was performed to assess left ventricular function.
      An incidental finding of a very large coronary sinus with a diameter of 4.8 cm
      was seen, raising a suspicion for the possibility of a persistent left superior
      vena cava (PLSVC) (Figure 1). Additional pertinent positive findings included a
      massively dilated right atrium (estimated volume: 538 mL), dilated tricuspid
      annulus with poor leaflet coaptation, severe tricuspid regurgitation, and
      pulmonary artery systolic pressure (PASP) of 50 mmHg with an estimated mean right
      atrial pressure (RAP) of 25 mmHg. After agitated saline administration into the
      left brachial vein, there was immediate and sequential opacification of the
      dilated coronary sinus, right atrium, and right ventricle, confirming the
      presence of a PLSVC (Figure 2). CT angiography provided detailed anatomical and
      morphological characterization demonstrating drainage of the PLSVC into the
      gigantic coronary sinus and right-sided cardiac chambers and absence of other
      vascular or congenital anomaly (Figures 3 and 4).

PMID- 21088660
TI  - Antibiotic prophylaxis for infective endocarditis: ethical care in the era of
      revised guidelines.
AB  - Beginning in 1955, the American Heart Association recommended antibiotic
      prophylaxis among patients with certain structural heart diseases to decrease the
      likelihood of infective endocarditis (IE) following dental procedures. Over the
      ensuing 52 years, the American College of Cardiology/American Heart Association
      (ACC/AHA) guidelines were revised to address gastrointestinal and genitourinary
      procedures and to modify the assessment of relative risks and specific regimens
      for prophylaxis. Throughout the various revisions, prophylaxis was recommended
      for individuals who were at increased risk of developing IE based on best
      evidence and consensus opinion, albeit in the absence of randomized controlled
      trials. In 2007, the AHA published a revised guideline statement dramatically
      restricting its recommendations for antibiotic prophylaxis against IE. In 2008,
      these views were incorporated in an ACC/AHA guideline update on the management of
      patients with heart valve disease. The revisions represent a dramatic shift in
      terms of the patients for whom antibiotic prophylaxis is recommended and the
      procedures for which it is recommended. What is striking about the new guidelines
      is that the change in recommendations was based not on new data, but on a change
      in philosophy despite the lack of new data. To some degree, the arguments for and
      against antibiotic prophylaxis become those of philosophy, ethics, and the role
      of evidence-based medicine. This manuscript attempts to briefly examine those
      arguments and discuss why the revised guidelines may fail to respect the ethical
      principles of beneficence and patient autonomy.

PMID- 21088661
TI  - Antiseptic activity and phenolic constituents of the aerial parts of Vitex
      negundo var. cannabifolia.
AB  - Four phenolics, salviaplebeiaside (1), gamma-tocopherol (2), chrysosplenol-D (4),
      and isovitexin (5), along with alpha-tocoquinone (3) and beta-sitosterol (6) were
      isolated from the aerial parts of Vitex negundo var. cannabifolia. The isolation
      was performed using bio-assay tracking experiments. The structures of compounds 1
      5 were established by spectroscopic means. The antibacterial activities of the
      compounds were assessed against Escherichia coli, Bacillus subtilis, Micrococcus
      tetragenus and Pseudomonas fluorescens. Chrysosplenol-D (4) exhibited activities
      against all the four spoilage microorganisms.

PMID- 21088662
TI  - The pharmacokinetics of raloxifene and its interaction with apigenin in rat.
AB  - PURPOSE: Raloxifene is a selective estrogen receptor modulator which is
      structurally similar to tamoxifen. As flavonoids can interact with raloxifene in
      vitro, we evaluated the in vivo pharmacokinetics of raloxifene in rats when co
      administered with apigenin. METHODS: The pharmacokinetics of raloxifene in the
      absence or presence of apigenin was investigated in rats after different dosage
      regimens. The plasma concentrations before and after enzymatic hydrolysis were
      analyzed by HPLC, and the pharmacokinetic profiles of raloxifene administered
      alone and in combination with apigenin were compared. RESULTS: Co-administration
      of apigenin with raloxifene in a 1:2 ratio by weight resulted in a 55% and 37%
      increase in the C(max) and AUC of intact raloxifene, respectively. When equal
      proportions of raloxifene and apigenin (1:1) were administered, the C(max) and
      AUC of intact raloxifene were increased by 173% and 97% respectively. This
      increase in intact raloxifene was not associated with an increase in total
      raloxifene (intact plus conjugated raloxifene) because AUC and C(max) of total
      raloxifene when administered alone or in combination with apigenin were found to
      be similar. The results indicated that apigenin inhibited the glucuronidation and
      sulfation of raloxifene in the intestine bringing about an increased
      bioavailability of the drug. CONCLUSIONS: The results showed that apigenin
      decreased the first-pass metabolism of raloxifene but did not increase its
      absorption from the gastrointestinal tract.

PMID- 21088663
TI  - Prevention of perinatal group B streptococcal disease--revised guidelines from
      CDC, 2010.
AB  - Despite substantial progress in prevention of perinatal group B streptococcal
      (GBS) disease since the 1990s, GBS remains the leading cause of early-onset
      neonatal sepsis in the United States. In 1996, CDC, in collaboration with
      relevant professional societies, published guidelines for the prevention of
      perinatal group B streptococcal disease (CDC. Prevention of perinatal group B
      streptococcal disease: a public health perspective. MMWR 1996;45[No. RR-7]);
      those guidelines were updated and republished in 2002 (CDC. Prevention of
      perinatal group B streptococcal disease: revised guidelines from CDC. MMWR
      2002;51[No. RR-11]). In June 2009, a meeting of clinical and public health
      representatives was held to reevaluate prevention strategies on the basis of data
      collected after the issuance of the 2002 guidelines. This report presents CDC's
      updated guidelines, which have been endorsed by the American College of
      Obstetricians and Gynecologists, the American Academy of Pediatrics, the American
      College of Nurse-Midwives, the American Academy of Family Physicians, and the
      American Society for Microbiology. The recommendations were made on the basis of
      available evidence when such evidence was sufficient and on expert opinion when
      available evidence was insufficient. The key changes in the 2010 guidelines
      include the following: * expanded recommendations on laboratory methods for the
      identification of GBS, * clarification of the colony-count threshold required for
      reporting GBS detected in the urine of pregnant women, * updated algorithms for
      GBS screening and intrapartum chemoprophylaxis for women with preterm labor or
      preterm premature rupture of membranes, * a change in the recommended dose of
      penicillin-G for chemoprophylaxis, * updated prophylaxis regimens for women with
      penicillin allergy, and * a revised algorithm for management of newborns with
      respect to risk for early-onset GBS disease. Universal screening at 35-37 weeks'
      gestation for maternal GBS colonization and use of intrapartum antibiotic
      prophylaxis has resulted in substantial reductions in the burden of early-onset
      GBS disease among newborns. Although early-onset GBS disease has become
      relatively uncommon in recent years, the rates of maternal GBS colonization (and
      therefore the risk for early-onset GBS disease in the absence of intrapartum
      antibiotic prophylaxis) remain unchanged since the 1970s. Continued efforts are
      needed to sustain and improve on the progress achieved in the prevention of GBS
      disease. There also is a need to monitor for potential adverse consequences of
      intrapartum antibiotic prophylaxis (e.g., emergence of bacterial antimicrobial
      resistance or increased incidence or severity of non-GBS neonatal pathogens). In
      the absence of a licensed GBS vaccine, universal screening and intrapartum
      antibiotic prophylaxis continue to be the cornerstones of early-onset GBS disease
      prevention.

PMID- 21088665
TI  - Solving the NES problem.

PMID- 21088666
TI  - Unleashing cell death: the Fas-FADD complex.

PMID- 21088668
TI  - Association of poor physical function and cognitive dysfunction with high
      nocturnal blood pressure level in treated elderly hypertensive patients.
AB  - BACKGROUND: Our aim was to assess the association between poor physical function,
      cognitive dysfunction, and high nocturnal systolic blood pressure (SBP), all of
      which are markers of vulnerability or frailty in elderly persons. METHODS: In
      this cross-sectional study of 148 treated ambulatory elderly hypertensives (mean
      age: 75.5 years; 30% men), we evaluated 24-h BP levels, physical function
      (walking speed and timed up-and-go (TUG) tests), and mini-mental state
      examination (MMSE). Poor physical function or cognitive dysfunction was defined
      as a walking speed <=1.5 m/s or MMSE score <27 points (below the geometric means
      for either examination). RESULTS: Both slower walking speed and lower MMSE scores
      were associated with high nocturnal SBP level, but not with daytime SBP level,
      even after adjustment for significant covariates (P = 0.05 and P < 0.01,
      respectively). Slower walking speed was significantly associated with the
      diminished nocturnal SBP dipping independent of the 24-h BP levels (P = 0.02).
      Compared with the patients who performed well on both physical and cognitive
      tests, or with those who had either poor physical function or cognitive
      dysfunction but not both, patients with both poor physical function and cognitive
      dysfunction had significantly higher nocturnal SBP levels (120 vs. 123 vs. 128
      vs. 134 mm Hg; P = 0.008 for linear trend) and less marked nocturnal SBP dipping
      (-14.4 vs. -12.9 vs. -10.7 vs. -7.5%; P = 0.02 for linear trend) even after
      adjustment for significant covariates. CONCLUSION: Poor physical function and/or
      cognitive dysfunction could be valid markers likely to be associated with high
      nocturnal SBP, information which could help yield more refined prognosis for
      treated elderly hypertensives.

PMID- 21088669
TI  - Modulation of the BP response to diet by genes in the renin-angiotensin system
      and the adrenergic nervous system.
AB  - BACKGROUND: Essential hypertension results from the interaction of several
      genetic and environmental factors. Identification of genetic factors that
      modulate blood pressure (BP) response to interventions can lead to improved
      strategies for prevention and control. The purpose of this study was to identify
      genes that modulate BP response to dietary interventions. METHODS: We used data
      and samples collected in two randomized feeding studies to determine the extent
      to which genetic architecture is associated with the effect on BP of sodium
      intake and the Dietary Approaches to Stop Hypertension (DASH) dietary pattern.
      Participants in both trials were adults with above-optimal BP or unmedicated
      stage 1 hypertension. Genomic DNA was typed for several candidate genes. RESULTS:
      The effect of sodium intake on BP differed by genotype at the angiotensinogen,
      beta2-adrenergic receptor, and kallikrein loci. The effect of DASH dietary
      pattern on BP differed by genotype at the beta2-adrenergic receptor locus.
      CONCLUSIONS: These findings have implications for understanding the mechanism(s)
      through which diet affects BP, the heterogeneity of these effects, and the extent
      to which dietary interventions can modulate genetic predisposition.

PMID- 21088670
TI  - Vitamin D and subsequent systolic hypertension among women.
AB  - BACKGROUND: We examined data from a cohort of Caucasian women for evidence of an
      association between serum vitamin D (25-hydroxyvitamin D (25(OH)D)) insufficiency
      and greater risk of systolic hypertension in the population-based longitudinal
      Michigan Bone Health and Metabolism Study (MBHMS). METHODS: The cohort includes
      559 women aged 24-44 years in 1992; annual blood pressure (BP) measurements and
      data collection began in 1992 and is ongoing. A single-time serum 25(OH)D level
      was measured in 1993. Using logistic regression, vitamin D insufficiency (<80
      nmol/l) was related to systolic hypertension (>=140 mm Hg) measures identified in
      1993 and in 2007. Further, the relationship between vitamin D at baseline and the
      trajectory of systolic BP across the ensuing 14 years was assessed using
      longitudinal mixed modeling. RESULTS: Vitamin D insufficiency was not
      significantly associated with concurrent systolic hypertension in 1993 (odds
      ratio (OR) 1.3; 95% confidence interval (CI) (0.32, 5.1)). However, vitamin D
      insufficiency was associated with increased risk of systolic hypertension in 2007
      (OR 3.0; 95% CI (1.01, 8.7)) after adjusting for age, body fat percentage,
      antihypertensive medication use, and smoking. Baseline vitamin D status was not
      associated with rate of BP change over the 14-year period. CONCLUSIONS:
      Consistent with previous animal and human studies, we found a single-time measure
      of vitamin D among young adult women was associated with systolic hypertension 14
      years later. These prospective results suggest the need for further study of the
      role vitamin D insufficiency in early adulthood as a risk factor in subsequent
      hypertension among women.

PMID- 21088671
TI  - The contribution of hypertension to black-white differences in likelihood of
      coronary artery disease detected during elective angiography.
AB  - BACKGROUND: Black patients in the United States undergoing angiography for
      suspected coronary artery disease (CAD) have consistently been found to have less
      disease than whites. As the effects of hypertension are greater in blacks than
      whites, and hypertensive heart disease may mimic CAD and lead to catheterization,
      we examined the association between race and hypertension as an explanation for
      the disparities in angiographic CAD. METHODS: Using an academic hospital's
      institutional database, we studied patients undergoing first-time elective
      angiography from 2001 to 2008. Using multivariable logistic regression with data
      on patient demographics, CAD risk factors, and coronary stenoses, we compared
      rates of angiographic disease for blacks and whites, creating models separately
      for patients with and without hypertension. We then tested the significance of an
      interaction term between race and hypertension on angiographic findings. RESULTS:
      We identified 1,203 black and 2,538 white patients who underwent initial elective
      angiography. Black patients were less likely to have a significant stenotic
      lesion (>=50% stenosis in the left main artery or >=70% stenosis elsewhere) than
      whites (adjusted risk ratio 0.65; 95% confidence interval (CI) 0.55-0.75). Among
      patients with hypertension this difference was exaggerated (adjusted risk ratio
      0.60; 95% CI 0.51-0.71). However, among patients without hypertension, the risk
      of having a significant lesion was similar in blacks and whites (adjusted risk
      ratio 0.97; 95% CI 0.67-1.37). The interaction term for race and hypertension was
      confirmed as statistically significant. CONCLUSIONS: Among patients electively
      referred for angiography, hypertension, and its effects may contribute to the
      lower rate of CAD found in blacks compared to whites.

PMID- 21088673
TI  - Daily red wine consumption improves vascular function by a soluble guanylyl
      cyclase-dependent pathway.
AB  - BACKGROUND: Polyphenols in red wine are supposed to improve endothelial function.
      We investigated whether daily red wine consumption improves in-vivo vascular
      function by reducing endothelin-1 (ET-1). Additional pathways mediating this
      effect were studied using porcine coronary arteries (PCAs). METHODS: Eighteen
      young healthy women drank red wine daily for 3 weeks. Vascular function was
      evaluated by determining forearm blood flow (FBF) responses to endothelium
      dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside
      (SNP)) vasodilators. PCAs were suspended in organ baths and exposed to the
      endothelium-dependent vasodilator bradykinin, the nitric oxide (NO) donor S
      nitroso-N-acetyl-L,L-penicillamine (SNAP) and/or red wine extract (RWE). RESULTS:
      ACh-induced and SNP-induced FBF increases were equally enhanced after 3 weeks of
      red wine consumption, but an immediate enhancement (i.e., after drinking the
      first glass) was not observed. Vice versa, plasma ET-1 levels were not decreased
      after 3 weeks, but we observed an acute drop after drinking one glass of wine.
      RWE relaxed preconstricted PCAs in an endothelium-, NO-, and soluble guanylyl
      cyclase (sGC)/guanosine-3',5'-cyclic monophosphate (cGMP)-dependent manner. Short
      RWE exposure reduced the response to bradykinin and SNAP by inactivating sGC.
      This effect disappeared upon prolonged RWE exposure. CONCLUSIONS: The enhanced
      FBF response following 3 weeks of red wine consumption, but not after one glass,
      reflects a change in smooth muscle sensitivity. Alterations in sGC
      responsiveness/activity, rather than changes in ET-1, appear to underlie this
      phenomenon.

PMID- 21088672
TI  - Greater coffee intake in men is associated with steeper age-related increases in
      blood pressure.
AB  - BACKGROUND: Administration of caffeine or caffeinated coffee in laboratory and
      ambulatory settings results in small to moderate acute increases in blood
      pressure (BP). However, habitual coffee intake has not been linked conclusively
      to long-term increases in basal BP, and findings are inconsistent by sex. This
      study examined longitudinal relations of habitual coffee use to resting BP and
      pulse pressure. METHODS: In a sample of 2,442 participants from the Baltimore
      Longitudinal Study of Aging (BLSA), coffee consumption was used to predict
      resting systolic and diastolic BP and pulse pressure using longitudinal mixed
      effects regression models adjusted for age, education, antihypertensive, and
      antihyperlipidemic use, smoking, and body mass index (BMI). Analyses were
      stratified by sex (865 women and 1,577 men), and age and BMI were examined as
      possible effect modifiers. RESULTS: In men, we identified a significant three-way
      interaction among coffee intake (nonlinear), baseline age, and length of follow
      up for systolic BP (SBP) and pulse pressure. A significant interaction of coffee
      intake and BMI (nonlinear) was also noted for SBP in men. There were no
      significant relations of coffee intake to BP or pulse pressure in women.
      CONCLUSION: Greater coffee intake in men was associated with steeper age-related
      increases in SBP and pulse pressure, particularly beyond 70 years of age and in
      overweight to obese men.

PMID- 21088674
TI  - Association between NEDD4L gene and sodium lithium countertransport.
AB  - BACKGROUND: Sodium lithium countertransport (SLC) is an intermediate phenotype of
      essential hypertension. The aim of this study was to identify candidate genes for
      SLC by a strategy of combining gene expression profiling and linkage analysis,
      and to examine the association between the candidate gene and SLC as well as
      hypertension. METHODS: In order to identify SLC-related genes, the top 1% of the
      genes that were differentially expressed between high- and low-SLC groups in a
      gene expression microarray were compared with published SLC/hypertension gene
      linkage maps so as to identify regions of overlap. The association between the
      genetic variation in the candidate gene and the SLC and blood pressure phenotypes
      were further assessed in the Rochester Family Heart Study (RFHS) involving 1,815
      individuals of European ancestry, belonging to 252 pedigrees. RESULTS: Based on
      gene expression profiling and evidence from genome-wide linkage analysis, and in
      the light of its potential biochemical function, E3 ubiquitin-protein ligase
      NEDD4-like (NEDD4L) was identified as being both a positional and a functional
      candidate gene for SLC. The difference in expressions of NEDD4L between the high-
      and low-SLC groups was confirmed by reverse transcription-PCR (RT-PCR) analysis.
      After adjusting for age, sex, and body mass index (BMI), four single-nucleotide
      polymorphisms (SNPs) in NEDD4L were found to be associated with SLC (P <= 0.05).
      Further, haplotype analysis revealed that, after correction for multiple testing,
      one of the haplotypes (H2) was still significantly (P = 0.006) associated with
      SLC. CONCLUSIONS: The strategy of combining gene expression profiling and linkage
      analysis successfully guided us in identifying NEDD4L as a candidate gene
      involved in regulating SLC activity. Variations in the NEDD4L gene are associated
      with SLC activity.

PMID- 21088675
TI  - Lipid-heparin infusion suppresses the IL-10 response to trauma in subcutaneous
      adipose tissue in humans.
AB  - An imbalance between pro- and anti-inflammatory cytokine productions in adipose
      tissue is thought to contribute to chronic, systemic, low-grade inflammation and
      consequently to an increased risk of cardiovascular complications in obese and
      type 2 diabetic patients. Nonesterified fatty acids (NEFA), whose serum levels
      are elevated in such patients, have been shown to interfere with cytokine
      production in vitro. In order to evaluate the effects of elevated NEFA levels on
      cytokine production in adipose tissue in vivo we used an 18-gauge open-flow
      microperfusion (OFM) catheter to induce local inflammation in the subcutaneous
      adipose tissue (SAT) of healthy volunteers and to sample interstitial fluid (IF)
      specifically from the inflamed tissue. In two crossover studies, nine subjects
      received either an intravenous lipid-heparin infusion to elevate circulating NEFA
      levels or saline over a period of 28 h. The former increased the circulating
      levels of triglycerides (TGs), NEFA, glucose, and insulin over the study period.
      NEFA effects on locally induced inflammation were estimated by measuring the
      levels of a panel adipokines in the OFM probe effluent. Interleukin-6 (IL-6), IL
      8, tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1
      (MCP-1) levels increased during the study period but were not affected by lipid
      heparin infusion. In contrast, the level of IL-10, an anti-inflammatory cytokine,
      was significantly reduced during the final hour of lipid-heparin infusion
      (saline: 449.2 +/- 105.9 vs. lipid-heparin: 65.4 +/- 15.4 pg/ml; P = 0.02). These
      data provide the first in vivo evidence that elevated NEFA can modulate cytokine
      production by adipose tissue.

PMID- 21088677
TI  - Genetic tests: between risks and opportunities. The case of neurodegenerative
      diseases.

PMID- 21088678
TI  - Putting together rather than taking apart.
AB  - The town of Ascona in Switzerland, nestled on the northern shore of Lago
      Maggiore, hosted the 112 participants in the first systems biology meeting
      focused on developmental biology. The EMBO workshop was held between 16 and 20
      August and brought together a multidisciplinary group of scientists who use
      systems approaches to understand how the size and shape of multicellular
      organisms and organs are determined.

PMID- 21088679
TI  - Drug delivery: Nanobioconjugate shrinks brain tumours.

PMID- 21088680
TI  - Depression: In pursuit of happiness.

PMID- 21088681
TI  - G protein-coupled receptors: Breathing easier with bitter tastes.

PMID- 21088682
TI  - The stromal and haematopoietic antigen-presenting cells that reside in secondary
      lymphoid organs.
AB  - T cells encounter their cognate antigens in specialized compartments of secondary
      lymphoid organs (SLOs). There, dendritic cells (DCs) present self and non-self
      antigens to T cells, and promote immunity or tolerance depending on the
      availability of danger signals. Resident stromal cells orchestrate the
      interaction between T cells and DCs by recruiting them to T cell zones and
      guiding their migration within SLOs. Recent studies have shown that SLO-resident
      stromal cells also have a crucial role in tolerance induction in the periphery.
      In this Review, we discuss the roles of SLO-resident DCs and stromal cells in
      shaping T cell responses.

PMID- 21088685
TI  - The memory paradox.
AB  - Declarative and emotional memories are key to quality of life and day-to-day
      functioning. The absence of memory or the inability to recall memories properly
      in an emotional context leads to dysfunction but, paradoxically, memories that
      generate too much emotion can be equally disabling.

PMID- 21088683
TI  - Sterile inflammation: sensing and reacting to damage.
AB  - Over the past several decades, much has been revealed about the nature of the
      host innate immune response to microorganisms, with the identification of pattern
      recognition receptors (PRRs) and pathogen-associated molecular patterns, which
      are the conserved microbial motifs sensed by these receptors. It is now apparent
      that these same PRRs can also be activated by non-microbial signals, many of
      which are considered as damage-associated molecular patterns. The sterile
      inflammation that ensues either resolves the initial insult or leads to disease.
      Here, we review the triggers and receptor pathways that result in sterile
      inflammation and its impact on human health.

PMID- 21088686
TI  - From Systematic Reviews to Clinical Recommendations for Evidence-Based Health
      Care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR)
      for Grading of Clinical Relevance.
AB  - Research synthesis seeks to gather, examine and evaluate systematically research
      reports that converge toward answering a carefully crafted research question,
      which states the problem patient population, the intervention under
      consideration, and the clinical outcome of interest. The product of the process
      of systematically reviewing the research literature pertinent to the research
      question thusly stated is the "systematic review".The objective and transparent
      approach of the systematic review aims to minimize bias. Most systematic reviews
      yield quantitative analyses of measurable data (e.g., acceptable sampling
      analysis, meta-analysis). Systematic reviews may also be qualitative, while
      adhering to accepted standards for gathering, evaluating, and reporting evidence.
      Systematic reviews provide highly rated recommendations for evidence-based health
      care; but, systematic reviews are not equally reliable and successful in
      minimizing bias.Several instruments are available to evaluate the quality of
      systematic reviews. The 'assessment of multiple systematic reviews' (AMSTAR) was
      derived from factor analysis of the most relevant items among them. AMSTAR
      consists of eleven items with good face and content validity for measuring the
      methodological quality of systematic reviews, has been widely accepted and
      utilized, and has gained in reliability, reproducibility. AMSTAR does not produce
      quantifiable assessments of systematic review quality and clinical relevance. In
      this study, we have revised the AMSTAR instrument, detracting nothing from its
      content and construct validity, and utilizing the very criteria employed in the
      development of the original tool, with the aim of yielding an instrument that can
      quantify the quality of systematic reviews. We present validation data of the
      revised AMSTAR (R-AMSTAR), and discuss its implications and application in
      evidence-based health care.

PMID- 21088684
TI  - The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease.
AB  - Parkinson's disease, like many common age-related conditions, is now recognized
      to have a substantial genetic component. Here, I discuss how mutations in a large
      complex gene--leucine-rich repeat kinase 2 (LRRK2)--affect protein function, and
      I review recent evidence that LRRK2 mutations affect pathways that involve other
      proteins that have been implicated in Parkinson's disease, specifically alpha
      synuclein and tau. These concepts can be used to understand disease processes and
      to develop therapeutic opportunities for the treatment of Parkinson's disease.

PMID- 21088687
TI  - School-Based Screening: A Population-Based Approach to Inform and Monitor
      Children's Mental Health Needs.
AB  - School-based mental health professionals often conduct assessments and provide
      interventions on an individual basis to students with significant needs. However,
      due to increasingly limited resources and continuing high levels of need, a shift
      in service delivery is warranted. Efforts to move school psychological services
      from reactive and individual, to preventive and universal are ongoing. To further
      service delivery change, school-based mental health professionals can engage in
      systematic periodic mental health screening of all children. This article will
      (a) discuss screening for risk of emotional and behavior problems from a
      population-based approach, (b) describe how screening data can identify and
      monitor the needs of students, schools, and communities, and (c) provide future
      directions for screening practices. As continued changes to service delivery are
      imminent, information on how to utilize school-based screening data will be
      particularly valuable to mental health professionals working with or within
      schools.

PMID- 21088689
TI  - QSRR Models for Kovats' Retention Indices of a Variety of Volatile Organic
      Compounds on Polar and Apolar GC Stationary Phases Using Molecular Connectivity
      Indexes.
AB  - Quantitative structure-retention relationship (QSRR) approaches, based on
      molecular connectivity indices are useful to predict the gas chromatography of
      Kovats relative retention indices (GC-RRIs) of 132 volatile organic compounds
      (VOCs) on different 12 (4 apolar and 8 polar) stationary phases (C(67), C(103),
      C(78), C(infinity), POH, TTF, MTF, PCL, PBR, TMO, PSH and PCN) at 130  degrees C.
      Full geometry optimization based on Austin model 1 semi-empirical molecular
      orbital method was carried out. The sets of 30 molecular descriptors were derived
      directly from the topological structures of the compounds from DRAGON program. By
      means of the final variable selection method, which is elimination selection
      stepwise regression algorithms, three optimal descriptors were selected to
      develop a QSRR model to predict the RRI of organic compounds on each stationary
      phase with a correlation coefficient between 0.9378 and 0.9673 and a leave-one
      out cross-validation correlation coefficient between 0.9325 and 0.9653. The root
      mean squares errors over different 12 phases were within the range of 0.0333
      0.0458. Furthermore, the accuracy of all developed models was confirmed using
      procedures of Y-randomization, external validation through an odd-even number and
      division of the entire dataset into training and test sets. A successful
      interpretation of the complex relationship between GC RRIs of VOCs and the
      chemical structures was achieved by QSRR. The three connectivity indexes in the
      models are also rationally interpreted, which indicated that all organic
      compounds' RRI was precisely represented by molecular connectivity indexes.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1365/s10337-010-1741-4) contains supplementary material, which is
      available to authorized users.

PMID- 21088688
TI  - Effects of macromolecular crowding on intracellular diffusion from a single
      particle perspective.
AB  - Compared to biochemical reactions taking place in relatively well-defined aqueous
      solutions in vitro, the corresponding reactions happening in vivo occur in
      extremely complex environments containing only 60-70% water by volume, with the
      remainder consisting of an undefined array of bio-molecules. In a biological
      setting, such extremely complex and volume-occupied solution environments are
      termed 'crowded'. Through a range of intermolecular forces and pseudo-forces,
      this complex background environment may cause biochemical reactions to behave
      differently to their in vitro counterparts. In this review, we seek to highlight
      how the complex background environment of the cell can affect the diffusion of
      substances within it. Engaging the subject from the perspective of a single
      particle's motion, we place the focus of our review on two areas: (1)
      experimental procedures for conducting single particle tracking experiments
      within cells along with methods for extracting information from these
      experiments; (2) theoretical factors affecting the translational diffusion of
      single molecules within crowded two-dimensional membrane and three-dimensional
      solution environments. We conclude by discussing a number of recent publications
      relating to intracellular diffusion in light of the reviewed material.

PMID- 21088690
TI  - Racial differences in smoking abstinence rates in a multicenter, randomized, open
      label trial in the United States.
AB  - BACKGROUND: This study evaluates differences in smoking abstinence between white
      and minority smokers using pharmaceutical aids. METHODS: This is an analysis of
      data from a multi-center, randomized, clinical trial conducted in the United
      States. Of the 1,684 subjects randomized to one of three medications (nicotine
      inhaler, bupropion, or a combination of both), 60% were women and 10% were
      minority races. RESULTS: Factors associated with a decreased likelihood of
      smoking at 12 weeks were older age (OR = 0.971, p < 0.0001), being married (OR =
      0.678, p = 0.0029), using bupropion SR (OR = 0.480, p < 0.0001), and using
      combination therapy (OR = 0.328, p < 0.0001). Factors associated with an
      increased likelihood of smoking were higher tobacco dependence scores (OR =
      1.244, p < 0.0001), prior quit attempts (OR = 1.812, p = 0.004), and being a
      minority (OR = 1.849, p = 0.0083). Compared to white smokers, minority smokers
      were significantly older at time of study entry (46 vs. 42 years, p < 0.0001),
      less likely to be married (35% vs. 59%, p < 0.0001), older at smoking initiation
      (21 vs. 19 years of age, p < 0.0001), and had a lower abstinence rate (16% vs.
      26%, p = 0.0065). CONCLUSION: Regardless of the treatment used, minority smokers
      in the US have lower smoking abstinence after treatment for tobacco dependence.
      Future research should focus on the improvement in treatment strategies for
      minority smokers.

PMID- 21088691
TI  - Gender and ethnic disparities contributing to overweight in California
      adolescents.
AB  - PURPOSE: To explore differences in health behaviors and factors contributing to
      overweight among 12 to 17 year olds in California. METHODS: Data from the 2005
      California Health Interview Survey for 3,315 adolescents self-identified as
      Latino, Asian, or white were reviewed. Adolescents reported their weight, height,
      gender, ethnicity, parents' educational level, household income, physical
      activity, sedentary activity, breakfast consumption, and family meals. RESULTS:
      Overall 34% of boys and 22% of girls in this study were overweight (>85th
      percentile for age and gender). Approximately 38% of Latinos, 25% of whites, and
      16% of Asians were overweight. Latinos were more than twice as likely to be
      overweight as whites (2.07) and Asians (2.53). Younger adolescents (12-13 years
      old) and adolescents whose family income is less than 200% of the federal poverty
      level were more likely to be overweight. Low level of parental education is a
      risk factor for Latino and Asian girls and white and Latino boys. White girls
      with a lower socioeconomic status and white boys with more than 2 h daily of
      television, video, and computer time were more likely to be overweight.
      CONCLUSION: Results suggest gender and ethnic variations in factors that
      contribute to overweight in California adolescents. To influence the current
      overweight epidemic, clinicians must develop culturally sensitive and gender
      specific interventions that address the unique needs of an ethnically diverse
      adolescent population.

PMID- 21088692
TI  - Socio-economic inequalities in physical activity practice among Italian children
      and adolescents: a cross-sectional study.
AB  - AIM: The aim of the study was to evaluate whether socio-economic inequalities in
      the practice of physical activity existed among children and adolescents, using
      different indicators of socio-economic status (SES). SUBJECTS AND METHODS: Data
      were derived from the Italian National Health Interview Survey carried out in
      2004-2005, which examined a large random sample of the Italian population using
      both an interviewer-administered and a self-compiled questionnaire. This study
      was based on a sample of 15,216 individuals aged 6-17 years. The practice of
      physical activity was measured on the basis of questions regarding frequency and
      intensity of activity during leisure time over the past 12 months. Parents'
      educational and occupational level, as well as family's availability of material
      resource, were used as indicators of SES. Multivariable logistic regression
      analyses were performed to estimate the contribution of each SES indicator to the
      practice of physical activity, adjusting for potential confounding factors. The
      results of the regression models are expressed as odds ratio (OR) with 95%
      confidence intervals (95% CI). RESULTS: About 64% of children and adolescents in
      the sample declared that they participated in moderate or vigorous physical
      activity at least once a week. After adjustment for gender, age, parental
      attitudes towards physical activity and geographical area, the practice of
      physical activity increased with higher parental educational and occupational
      level and greater availability of material resources. Children and adolescents
      whose parents held a middle or high educational title were 80% more likely to
      practice moderate or vigorous physical activity than subjects whose parents had a
      lower level of education (OR = 1.80, 95% CI: 1.40-2.33), while subjects with
      unemployed parents had an odds of practicing moderate or vigorous physical
      activity 0.43 times that of those children whose parents belonged to the top job
      occupation category (administrative/professionals). Socio-economic differences
      were about the same when the practice of vigorous physical activity only was
      considered instead of that of moderate or vigorous physical activity. CONCLUSION:
      Interventions that promote the practice of physical activity, and especially
      those aimed at the wider physical and social environment, are strongly needed to
      contrast socio-economic differences in physical activity among children and
      adolescents.

PMID- 21088693
TI  - Saving lives in road traffic-ethical aspects.
AB  - AIM: This article aims at giving an overview of five ethical problem areas
      relating to traffic safety, thereby providing a general framework for analysing
      traffic safety from an ethical perspective and encouraging further discussion
      concerning problems, policies and technology in this area. SUBJECTS AND METHODS:
      The problems presented in the article are criminalisation, paternalism, privacy,
      justice and responsibility, and the reasons for choosing these are the following.
      First, they are all important areas in moral philosophy. Second, they are fairly
      general and it should be possible to categorise more specific problems under
      these headings. Ethical aspects of road traffic have not received the
      philosophical attention they deserve. Every year, more than 1 million people die
      globally in traffic accidents, and 20 to 50 million people are injured. Ninety
      per cent of the road traffic fatalities occur in low- and middle-income
      countries, where it is a growing problem. Politics, economics, culture and
      technology affect the number of fatalities and injuries, and the measures used to
      combat deaths in traffic as well as the role of road traffic should be ethically
      scrutinised. The topics are analysed and discussed from a moral-philosophical
      perspective, and the discussion includes both theory and applications. RESULTS
      AND CONCLUSION: The author concludes with some thoughts on how the ethical
      discussion can be included in the public debate on how to save lives in road
      traffic. People in industrialised societies are so used to road traffic that it
      is almost seen as part of nature. Consequently, we do not acknowledge that we can
      introduce change and that we can affect the role we have given road traffic and
      cars. By acknowledging the ethical aspects of road traffic and illuminating the
      way the choices society makes are ethically charged, it becomes clear that there
      are alternative ways to design the road traffic system. The most important
      general conclusion is that discussion concerning these alternative ways of
      designing the system should be encouraged.

PMID- 21088694
TI  - The detection of communicative signals directed at the self in infant prefrontal
      cortex.
AB  - A precondition for successful communication between people is the detection of
      signals indicating the intention to communicate, such as eye contact or calling a
      person's name. In adults, establishing communication by eye contact or calling a
      person's name results in overlapping activity in right prefrontal cortex,
      suggesting that, regardless of modality, the intention to communicate is detected
      by the same brain region. We measured prefrontal cortex responses in 5-month-olds
      using near-infrared spectroscopy (NIRS) to examine the neural basis of detecting
      communicative signals across modalities in early development. Infants watched
      human faces that either signaled eye contact or directed their gaze away from the
      infant, and they also listened to voices that addressed them with their own name
      or another name. The results revealed that infants recruit adjacent but non
      overlapping regions in the left dorsal prefrontal cortex when they process eye
      contact and own name. Moreover, infants that responded sensitively to eye contact
      in the one prefrontal region were also more likely to respond sensitively to
      their own name in the adjacent prefrontal region as revealed in a correlation
      analysis, suggesting that responding to communicative signals in these two
      regions might be functionally related. These NIRS results suggest that infants
      selectively process and attend to communicative signals directed at them.
      However, unlike adults, infants do not seem to recruit a common prefrontal region
      when processing communicative signals of different modalities. The implications
      of these findings for our understanding of infants' developing communicative
      abilities are discussed.

PMID- 21088695
TI  - Molecular and anatomical signatures of sleep deprivation in the mouse brain.
AB  - Sleep deprivation (SD) leads to a suite of cognitive and behavioral impairments,
      and yet the molecular consequences of SD in the brain are poorly understood.
      Using a systematic immediate-early gene (IEG) mapping to detect neuronal
      activation, the consequences of SD were mapped primarily to forebrain regions. SD
      was found to both induce and suppress IEG expression (and thus neuronal activity)
      in subregions of neocortex, striatum, and other brain regions. Laser
      microdissection and cDNA microarrays were used to identify the molecular
      consequences of SD in seven brain regions. In situ hybridization (ISH) for 222
      genes selected from the microarray data and other sources confirmed that robust
      molecular changes were largely restricted to the forebrain. Analysis of the ISH
      data for 222 genes (publicly accessible at http://sleep.alleninstitute.org)
      provided a molecular and anatomic signature of the effects of SD on the brain.
      The suprachiasmatic nucleus (SCN) and the neocortex exhibited differential
      regulation of the same genes, such that in the SCN genes exhibited time-of-day
      effects while in the neocortex, genes exhibited only SD and waking (W) effects.
      In the neocortex, SD activated gene expression in areal-, layer-, and cell type
      specific manner. In the forebrain, SD preferentially activated excitatory
      neurons, as demonstrated by double-labeling, except for striatum which consists
      primarily of inhibitory neurons. These data provide a characterization of the
      anatomical and cell type-specific signatures of SD on neuronal activity and gene
      expression that may account for the associated cognitive and behavioral effects.

PMID- 21088696
TI  - Transient Down-Regulation of Sound-Induced c-Fos Protein Expression in the
      Inferior Colliculus after Ablation of the Auditory Cortex.
AB  - We tested whether lesions of the excitatory glutamatergic projection from the
      auditory cortex (AC) to the inferior colliculus (IC) induce plastic changes in
      neurons of this nucleus. Changes in neuronal activation in the IC deprived
      unilaterally of the cortico-collicular projection were assessed by quantitative c
      Fos immunocytochemistry. Densitometry and stereology measures of sound-induced c
      Fos immunoreactivity in the IC showed diminished labeling at 1, 15, 90, and 180
      days after lesions to the AC suggesting protein down-regulation, at least up to
      15 days post-lesion. Between 15 and 90 days after the lesion, c-Fos labeling
      recovers, approaching control values at 180 days. Thus, glutamatergic excitation
      from the cortex maintains sound-induced activity in neurons of the IC.
      Subdivisions of this nucleus receiving a higher density of cortical innervation
      such as the dorsal cortex showed greater changes in c-Fos immunoreactivity,
      suggesting that the anatomical strength of the projection correlates with effect
      strength. Therefore, after damage of the corticofugal projection, neurons of the
      IC down-regulate and further recover sound-induced c-Fos protein expression. This
      may be part of cellular mechanisms aimed at balancing or adapting neuronal
      responses to altered synaptic inputs.

PMID- 21088697
TI  - Oral and gastrointestinal sensing of dietary fat and appetite regulation in
      humans: modification by diet and obesity.
AB  - Dietary fat interacts with receptors in both the oral cavity and the
      gastrointestinal (GI) tract to regulate fat and energy intake. This review
      discusses recent developments in our understanding of the mechanisms underlying
      the effects of fat, through its digestive products, fatty acids (FAs), on GI
      function and energy intake, the role of oral and intestinal FA receptors, and the
      implications that changes in oral and small intestinal sensitivity in response to
      ingested fat may have for the development of obesity.

PMID- 21088698
TI  - Nucleus Accumbens Core and Shell are Necessary for Reinforcer Devaluation Effects
      on Pavlovian Conditioned Responding.
AB  - The nucleus accumbens (NA) has been hypothesized to be part of a circuit in which
      cue-evoked information about expected outcomes is mobilized to guide behavior.
      Here we tested this hypothesis using a Pavlovian reinforcer devaluation task,
      previously applied to assess outcome-guided behavior after damage to regions such
      as the orbitofrontal cortex and amygdala that send projections to NA. Rats with
      sham lesions or neurotoxic lesions of either the core or shell subdivision of NA
      were trained to associate a 10-s CS+ with delivery of three food pellets. After
      training, half of the rats in each lesion group received food paired with illness
      induced by LiCl injections; the remaining rats received food and illness
      unpaired. Subsequently, responding to the CS+ was assessed in an extinction probe
      test. Both sham and lesioned rats conditioned to the CS+ and formed a conditioned
      taste aversion. However only sham rats reduced their conditioned responding as a
      result of reinforcer devaluation; devalued rats with lesions of either core or
      shell showed levels of responding that were similar to lesioned, non-devalued
      rats. This impairment was not due to the loss of motivational salience conferred
      to the CS+ in lesioned rats as both groups responded similarly for the cue in
      conditioned reinforcement testing. These data suggest that NA core and shell are
      part of a circuit necessary for the use of cue-evoked information about expected
      outcomes to guide behavior.

PMID- 21088699
TI  - High field FMRI reveals thalamocortical integration of segregated cognitive and
      emotional processing in mediodorsal and intralaminar thalamic nuclei.
AB  - Thalamocortical loops, connecting functionally segregated, higher order cortical
      regions, and basal ganglia, have been proposed not only for well described motor
      and sensory regions, but also for limbic and prefrontal areas relevant for
      affective and cognitive processes. These functions are, however, more specific to
      humans, rendering most invasive neuroanatomical approaches impossible and
      interspecies translations difficult. In contrast, non-invasive imaging of
      functional neuroanatomy using fMRI allows for the development of elaborate task
      paradigms capable of testing the specific functionalities proposed for these
      circuits. Until recently, spatial resolution largely limited the anatomical
      definition of functional clusters at the level of distinct thalamic nuclei. Since
      their anatomical distinction seems crucial not only for the segregation of
      cognitive and limbic loops but also for the detection of their functional
      interaction during cognitive-emotional integration, we applied high resolution
      fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects
      for preceding attention as well as experience of erotic stimuli. We could
      demonstrate specific thalamic effects of general emotional arousal in mediodorsal
      nucleus and effects specific to preceding attention and expectancy in
      intralaminar centromedian/parafascicular complex. These thalamic effects were
      paralleled by specific coactivations in the head of caudate nucleus as well as
      segregated portions of rostral or caudal cingulate cortex and anterior insula
      supporting distinct thalamo-striato-cortical loops. In addition to predescribed
      effects of sexual arousal in hypothalamus and ventral striatum, high resolution
      fMRI could extent this network to paraventricular thalamus encompassing
      laterodorsal and parataenial nuclei. We could lend evidence to segregated
      subcortical loops which integrate cognitive and emotional aspects of basic human
      behavior such as sexual processing.

PMID- 21088700
TI  - Neuro-endocrine control of reproduction in hermaphroditic freshwater snails:
      mechanisms and evolution.
AB  - Invertebrates are used extensively as model species to investigate neuro
      endocrine processes regulating behaviors, and many of these processes may be
      extrapolated to vertebrates. However, when it comes to reproductive processes,
      many of these model species differ notably in their mode of reproduction. A point
      in case are simultaneously hermaphroditic molluscs. In this review I aim to
      achieve two things. On the one hand, I provide a comprehensive overview of the
      neuro-endocrine control of male and female reproductive processes in freshwater
      snails. Even though the focus will necessarily be on Lymnaea stagnalis, since
      this is the best-studied species in this respect, extensions to other species are
      made wherever possible. On the other hand, I will place these findings in the
      actual context of the whole animal, after all these are simultaneous
      hermaphrodites. By considering the hermaphroditic situation, I uncover a numbers
      of possible links between the regulation of the two reproductive systems that are
      present within this animal, and suggest a few possible mechanisms via which this
      animal can effectively switch between the two sexual roles in the flexible way
      that it does. Evidently, this opens up a number of new research questions and
      areas that explicitly integrate knowledge about behavioral decisions (e.g.,
      mating, insemination, egg laying) and sexual selection processes (e.g., mate
      choice, sperm allocation) with the actual underlying neuronal and endocrine
      mechanisms required for these processes to act and function effectively.

PMID- 21088702
TI  - Overcoming the Effects of Variation in Infant Speech Segmentation: Influences of
      Word Familiarity.
AB  - Previous studies have shown that 7.5-month-olds can track and encode words in
      fluent speech, but they fail to equate instances of a word that contrast in
      talker gender, vocal affect, and fundamental frequency. By 10.5 months, they
      succeed at generalizing across such variability, marking a clear transition
      period during which infants' word recognition skills become qualitatively more
      mature. Here we explore the role of word familiarity in this critical transition
      and, in particular, whether words that occur frequently in a child's listening
      environment (i.e., "Mommy" and "Daddy") are more easily recognized when they
      differ in surface characteristics than those that infants have not previously
      encountered (termed nonwords). Results demonstrate that words are segmented from
      continuous speech in a more linguistically mature fashion than nonwords at 7.5
      months, but at 10.5 months, both words and nonwords are segmented in a relatively
      mature fashion. These findings suggest that early word recognition is facilitated
      in cases where infants have had significant exposure to items, but at later
      stages, infants are able to segment items regardless of their presumed
      familiarity.

PMID- 21088701
TI  - The "Connection" Between HIV Drug Resistance and RNase H.
AB  - Currently, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside
      reverse transcriptase inhibitors (NNRTIs) are two classes of antiretroviral
      agents that are approved for treatment of HIV-1 infection. Since both NRTIs and
      NNRTIs target the polymerase (pol) domain of reverse transcriptase (RT), most
      genotypic analysis for drug resistance is limited to the first ~300 amino acids
      of RT. However, recent studies have demonstrated that mutations in the C-terminal
      domain of RT, specifically the connection subdomain and RNase H domain, can also
      increase resistance to both NRTIs and NNRTIs. In this review we will present the
      potential mechanisms by which mutations in the C-terminal domain of RT influence
      NRTI and NNRTI susceptibility, summarize the prevalence of the mutations in these
      regions of RT identified to date, and discuss their importance to clinical drug
      resistance.

PMID- 21088703
TI  - Metaxin deficiency alters mitochondrial membrane permeability and leads to
      resistance to TNF-induced cell killing.
AB  - Metaxin, a mitochondrial outer membrane protein, is critical for TNF-induced cell
      death in L929 cells. Its deficiency, caused by retroviral insertion-mediated
      mutagenesis, renders L929 cells resistance to TNF killing. In this study, we
      further characterized metaxin deficiency-caused TNF resistance in parallel with
      Bcl-X(L) overexpression-mediated death resistance. We did not find obvious change
      in mitochondria membrane potential in metaxin-deficient (Met(mut)) and Bcl-X(L)
      overexpressing cells, but we did find an increase in the release rate of the
      mitochondrial membrane potential probe rhodamine 123 (Rh123) that was preloaded
      into mitochondria. In addition, overexpression of a function-interfering mutant
      of metaxin (MetaDeltaTM/C) or Bcl-X(L) in MCF-7.3.28 cells also resulted in an
      acquired resistance to TNF killing and a faster rate of Rh123 release, indicating
      a close correlation between TNF resistance and higher rates of the dye release
      from the mitochondria. The release of Rh123 can be controlled by the
      mitochondrial membrane permeability transition (PT) pore, as targeting an inner
      membrane component of the PT pore by cyclosporin A (CsA) inhibited Rh123 release.
      However, metaxin deficiency and Bcl-X(L) overexpression apparently affect Rh123
      release from a site(s) different from that of CsA, as CsA can overcome their
      effect. Though both metaxin and Bcl-X(L) appear to function on the outer
      mitochondrial membrane, they do not interact with each other. They may use
      different mechanisms to increase the permeability of Rh123, since previous
      studies have suggested that metaxin may influence certain outer membrane porins
      while Bcl-X(L) may form pores on the outer membrane. The alteration of the
      mitochondrial outer membrane properties by metaxin deficiency and Bcl-X(L)
      overexpression, as indicated by a quicker Rh123 release, may be helpful in
      maintaining mitochondrial integrity.

PMID- 21088704
TI  - Catastrophic Appraisal and Perceived Control as Moderators of Treatment Response
      in Panic Disorder.
AB  - The purpose of this study was to examine the moderating effects of cognitive risk
      factors in two mechanistically-distinct interventions. Forty-one patients with
      panic disorder and agoraphobia were randomly assigned to receive training aimed
      at altering respiration (Capnometry-assisted respiratory training, CART) or
      symptom appraisal (cognitive skill training, CT). Using a mixed effects
      regression model, we assessed whether reductions in panic symptom severity (PDSS)
      were moderated by the variables of interest. While improvement in PDSS did not
      differ among treatment modalities, moderating effects emerged. Individuals with
      greater initial levels of misappraisal showed smaller reduction in PDSS when
      receiving CT, but larger reduction when receiving CART. Greater lack of perceived
      control was predictive of worse outcome in CART, but better outcome in CT. Better
      homework compliance was related to greater reductions in PDSS irrespective of
      condition. The findings illustrate the complexity of moderating influences within
      and between distinct interventions.

PMID- 21088705
TI  - Parents' Feelings Towards Their Adoptive and Non-Adoptive Children.
AB  - In the current study, we examined parent gender differences in feelings
      (negativity and positivity) and perceptions of child behavioural and emotional
      problems in adoptive and biological parent-child dyads. In a sample of 85
      families, we used a novel within-family adoption design in which one child was
      adopted and one child was a biological child of the couple, and tested whether
      the links between parent feelings and child maladjustment included effects of
      passive gene-environment correlation. Parents reported more negativity and less
      positivity as well as higher levels of externalizing behaviour for the adopted
      child compared to the non-adopted child, although effect sizes were small and no
      longer statistically significant after correcting for multiple comparisons.
      Fathers and mothers did not differ significantly in their reports of positive and
      negative feelings towards their children or in regard to child externalizing and
      internalizing behaviours. The correlations between parental negativity and
      positivity and child externalizing and internalizing were similar for fathers and
      mothers, and for adopted and non-adopted children. The findings suggest similar
      parent-child relationship processes for fathers and mothers, and that genetic
      transmission of behaviour from parent to child does not account for the
      association between parental warmth and hostility and child-adjustment problems.

PMID- 21088706
TI  - Corticostriatal projection neurons - dichotomous types and dichotomous functions.
AB  - The mammalian striatum receives its main excitatory input from the two types of
      cortical pyramidal neurons of layer 5 of the cerebral cortex - those with only
      intratelencephalic connections (IT-type) and those sending their main axon to the
      brainstem via the pyramidal tract (PT-type). These two neurons types are present
      in layer 5 of all cortical regions, and thus they appear to project together to
      all parts of striatum. These two neuron types, however, differ genetically,
      morphologically, and functionally, with IT-type neurons conveying sensory and
      motor planning information to striatum and PT-type neurons conveying an efference
      copy of motor commands (for motor cortex at least). Anatomical and physiological
      data for rats, and more recent data for primates, indicate that these two
      cortical neuron types also differ in their targeting of the two main types of
      striatal projection neurons, with the IT-type input preferentially innervating
      direct pathway neurons and the PT-type input preferentially innervating indirect
      pathway striatal neurons. These findings have implications for understanding how
      the direct and indirect pathways carry out their respective roles in movement
      facilitation and movement suppression, and they have implications for
      understanding the role of corticostriatal synaptic plasticity in adaptive motor
      control by the basal ganglia.

PMID- 21088707
TI  - Influences of Neural Pathway Integrity on Children's Response to Reading
      Instruction.
AB  - As the education field moves toward using responsiveness to intervention to
      identify students with disabilities, an important question is the degree to which
      this classification can be connected to a student's neurobiological
      characteristics. A few functional neuroimaging studies have reported a
      relationship between activation and response to instruction; however, whether a
      similar correlation exists with white matter (WM) is not clear. To investigate
      this issue, we acquired high angular resolution diffusion images from a group of
      first grade children who differed in their levels of responsiveness to a year
      long reading intervention. Using probabilistic tractography, we calculated the
      strength of WM connections among nine cortical regions of interest and correlated
      these estimates with participants' scores on four standardized reading measures.
      We found eight significant correlations, four of which were connections between
      the insular cortex and angular gyrus. In each of the correlations, a relationship
      with children's response to intervention was evident.

PMID- 21088708
TI  - Brain Activations to Emotional Pictures are Differentially Associated with
      Valence and Arousal Ratings.
AB  - Several studies have investigated the neural responses triggered by emotional
      pictures, but the specificity of the involved structures such as the amygdala or
      the ventral striatum is still under debate. Furthermore, only few studies
      examined the association of stimuli's valence and arousal and the underlying
      brain responses. Therefore, we investigated brain responses with functional
      magnetic resonance imaging of 17 healthy participants to pleasant and unpleasant
      affective pictures and afterwards assessed ratings of valence and arousal. As
      expected, unpleasant pictures strongly activated the right and left amygdala, the
      right hippocampus, and the medial occipital lobe, whereas pleasant pictures
      elicited significant activations in left occipital regions, and in parts of the
      medial temporal lobe. The direct comparison of unpleasant and pleasant pictures,
      which were comparable in arousal clearly indicated stronger amygdala activation
      in response to the unpleasant pictures. Most important, correlational analyses
      revealed on the one hand that the arousal of unpleasant pictures was
      significantly associated with activations in the right amygdala and the left
      caudate body. On the other hand, valence of pleasant pictures was significantly
      correlated with activations in the right caudate head, extending to the nucleus
      accumbens (NAcc) and the left dorsolateral prefrontal cortex. These findings
      support the notion that the amygdala is primarily involved in processing of
      unpleasant stimuli, particularly to more arousing unpleasant stimuli. Reward
      related structures like the caudate and NAcc primarily respond to pleasant
      stimuli, the stronger the more positive the valence of these stimuli is.

PMID- 21088709
TI  - From singing to speaking: facilitating recovery from nonfluent aphasia.
AB  - It has been reported for more than 100 years that patients with severe nonfluent
      aphasia are better at singing lyrics than they are at speaking the same words.
      This observation led to the development of melodic intonation therapy (MIT).
      However, the efficacy of this therapy has yet to be substantiated in a randomized
      controlled trial. Furthermore, its underlying neural mechanisms remain unclear.
      The two unique components of MIT are the intonation of words and simple phrases
      using a melodic contour that follows the prosody of speech and the rhythmic
      tapping of the left hand that accompanies the production of each syllable and
      serves as a catalyst for fluency. Research has shown that both components are
      capable of engaging fronto-temporal regions in the right hemisphere, thereby
      making MIT particularly well suited for patients with large left hemisphere
      lesions who also suffer from nonfluent aphasia. Recovery from aphasia can happen
      in two ways: either through the recruitment of perilesional brain regions in the
      affected hemisphere, with variable recruitment of right-hemispheric regions if
      the lesion is small, or through the recruitment of homologous language and speech
      motor regions in the unaffected hemisphere if the lesion of the affected
      hemisphere is extensive. Treatment-associated neural changes in patients
      undergoing MIT indicate that the unique engagement of right-hemispheric
      structures (e.g., the superior temporal lobe, primary sensorimotor, premotor and
      inferior frontal gyrus regions) and changes in the connections across these brain
      regions may be responsible for its therapeutic effect.

PMID- 21088710
TI  - Genetics of autism and mental retardation: A spoonful from the sea!

PMID- 21088711
TI  - Iranian human genome project: Overview of a research process among Iranian
      ethnicities.
AB  - The Human Genome Project (HGP) refers to the international scientific research
      program, formally begun in October 1990 and completed in 2003, mainly designated
      to discover all the human genes, analyzing the structure of human DNA and
      determining the location of all human genes and also making them accessible for
      further biological and medical investigations. With the appropriate rationale
      approach, a similar study has been held in Iran. The study of human genome among
      Iranian ethnicities (IHGP) has been attempted formally in 2000 through a detailed
      and fully programmed research among all the major ethnic groups by more than
      1,900 samples from all over Iran based on the main demographical and
      anthropological findings and formally known criteria considered for the
      international HGP. This paper overviewed the process of the research in the terms
      of program goals, primary data collection, research designation and methodology
      and also practical aspects and primary findings of the Iranian genome project and
      its progress during a nearly 5-year period.

PMID- 21088712
TI  - Mitochondrial DNA mutations and male infertility.
AB  - Infertility can be defined as difficulty in conceiving a child after 1 year of
      unprotected intercourse. Infertility can arise either because of the male factor
      or female factor or both. According to the current estimates, 15% of couples
      attempting their first pregnancy could not succeed. Infertility is either primary
      or secondary. Mitochondria have profound effect on all biochemical pathways,
      including the one that drivessperm motility. Sperm motility is heavily dependent
      on the ATP generated by oxidative phosphorylation in the mitochondrial sheath. In
      this review, the very positive role of mitochondrial genome's association with
      infertility is discussed.

PMID- 21088714
TI  - Genetic studies in children with intellectual disability and autistic spectrum of
      disorders.
AB  - Autism is one of the five disorders that falls under the umbrella of Pervasive
      Developmental Disorders (PDD) or Autism Spectrum Disorder (ASD), a category of
      neurological disorders characterized by "severe and pervasive impairment in
      several areas of development." ASD is characterized by varying degrees of
      impairment in communication skills, social interaction and restricted, repetitive
      stereotyped patterns of behavior. The five disorders under PDD are autistic
      disorder, Asperger's disorder, childhood disintegrative disorder, Rett's disorder
      and PDD-not otherwise specified. ASD can often be reliably detected by the age of
      3 years and, in some cases, as early as 18 months. The appearance of any warning
      signs of ASD is reason to have the child evaluated by a professional specializing
      in these disorders.

PMID- 21088713
TI  - APO-1/Fas gene: Structural and functional characteristics in systemic lupus
      erythematosus and other autoimmune diseases.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple
      organ systems. It is characterized by the presence of autoantibodies reactive
      against various self-antigens. Susceptibility to SLE is found to be associated
      with many major histocompatibility complex (MHC) and non-MHC genes, one of which
      is APO-1/Fas gene, which is present on chromosome 10 in humans. The APO-1/Fas
      promoter contains consensus sequences for binding of several transcription
      factors that affect the intensity of Fas expression in cells. The mutations in
      the APO-1/Fas promoter are associated with risk and severity in various
      autoimmune diseases and other malignancies. The APO-1/Fas receptor is expressed
      by many cell types. Two forms of APO-1/Fas protein that are involved in
      regulation of apoptosis have been identified. Fas receptor-mediated apoptosis
      plays a physiological and pathological role in killing of infected cell targets.
      In this review, we have focused on APO-1/Fas gene structure, promoter variants
      and its association with SLE and other autoimmune diseases. Functional aspects of
      Fas receptor in apoptosis are also discussed.

PMID- 21088715
TI  - Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian
      population and its association with 25-hydroxyvitamin D levels.
AB  - BACKGROUND: The VDR protein is at the centre of the vitamin D endocrine system, a
      complex physiological system with substantial feedback regulatory mechanisms
      involved in maintaining serum calcium and 1, 25 dihydroxy vitamin D3. Variations
      in VDR gene are shown to have implications in several diseases and have also been
      implicated as an important genetic factor affecting bone mass. AIM: To determine
      the frequency of Fok I and Taq I variants in healthy Indian individuals and its
      association with 25-OH-Vitamin D levels. SETTINGS AND DESIGN: Blood samples were
      collected from 143 unrelated normal individuals (Male-84 and Female-59) and their
      genotypes determined. MATERIALS AND METHODS: After amplification by polymerase
      chain reaction, each polymorphism was genotyped by restriction fragment length
      polymorphism. For 100 normal healthy individuals 25-hydroxyvitamin D estimation
      was done using DiaSorin kit method. STATISTICAL ANALYSIS: Graph pad software was
      used to calculate the P values from the Chi-square. RESULTS: Out of 143 samples
      analyzed for FokI and TaqI polymorphisms the following genotypic frequency was
      obtained FF 59%, Ff 36%, ff 5% and TT 49%, Tt 43%, tt 8% respectively.
      CONCLUSIONS: Results indicate that the distribution of the polymorphic loci Fok I
      and Taq I vary considerably not only in different populations, but also within
      India. Furthermore, when the genotypes were analyzed with respect to 25-OH
      Vitamin D levels, a significant association was seen for the Taq 1 SNP but not
      with the Fok I.

PMID- 21088716
TI  - Microsatellite diversity among the primitive tribes of India.
AB  - The present study was undertaken to determine the extent of diversity at 12
      microsatellite short tandem repeat (STR) loci in seven primitive tribal
      populations of India with diverse linguistic and geographic backgrounds. DNA
      samples of 160 unrelated individuals were analyzed for 12 STR loci by multiplex
      polymerase chain reaction (PCR). Gene diversity analysis suggested that the
      average heterozygosity was uniformly high ( >0.7) in these groups and varied from
      0.705 to 0.794. The Hardy-Weinberg equilibrium analysis revealed that these
      populations were in genetic equilibrium at almost all the loci. The overall G(ST)
      value was high (G(ST) = 0.051; range between 0.026 and 0.098 among the loci),
      reflecting the degree of differentiation/heterogeneity of seven populations
      studied for these loci. The cluster analysis and multidimensional scaling of
      genetic distances reveal two broad clusters of populations, besides Moolu Kurumba
      maintaining their distinct genetic identity vis-a-vis other populations. The
      genetic affinity for the three tribes of the Indo-European family could be
      explained based on geography and Language but not for the four Dravidian tribes
      as reflected by the NJT and MDS plots. For the overall data, the insignificant
      MANTEL correlations between genetic, linguistic and geographic distances suggest
      that the genetic variation among these tribes is not patterned along geographic
      and/or linguistic lines.

PMID- 21088717
TI  - GITR expression on T-cell receptor-stimulated human CD8 T cell in a JNK-dependent
      pathway.
AB  - Glucocorticoid-induced tumor necrosis factor receptor (TNFR) (GITR) family
      related gene is a member of the TNFR super family. GITR works as one of the
      immunoregulatory molecule on CD4(+) regulatory T cells and has an important role
      on cell survival or cell death in CD4(+) T cells. Little is known about the
      expression of GITR on human CD8(+) T cells on antigen-specific and non-specific
      activation. Here, we report that expression of GITR on human CD8(+) T cells on T
      cell receptor (TCR) (anti-CD3)-mediated stimulation is dependent on the JNK
      pathway. The activation of CD8(+) T cells was measured by the expression of IL-2
      receptor-alpha (CD25), GITR and by IFN-gamma production upon re-stimulation with
      anti-CD3 antibody. We studied the signaling pathway of such inducible expression
      of GITR on CD8(+) T cells. We found that a known JNK-specific inhibitor,
      SP600125, significantly down-regulates GITR expression on anti-CD3 antibody
      mediated activated CD8(+) T cells by limiting JNK phosphorylation. Subsequently,
      after stimulation of the CD8(+) cells, we tested for the production of IFN-gamma
      by the activated cells following restimulation with the same stimulus. It appears
      that the expression of GITR on activated human CD8(+) T cells might also be
      regulated through the JNK pathway when the activation is through TCR stimulation.
      Therefore, GITR serves as an activation marker on activated CD8(+) cells and
      interference with JNK phosphorylation, partially or completely, by varying the
      doses of SP600125 might have implications in CD8(+) cytotoxic T cell response in
      translational research.

PMID- 21088718
TI  - Natural selection among Kinnaura of the Himalayan highland: A comparative
      analysis with other Indian and Himalayan populations.
AB  - The present investigation on fertility and mortality differential among Kinnaura
      of the Himalayan highland is based on data collected from 160 post-menopausal
      women belonging to the middle and high altitude region of Kinnaur district of
      Himachal Pradesh (Indian Himalayas). Selection potential based on differential
      fertility and mortality was computed for middle-and high-altitude women.
      Irrespective of the methodology, the total index of selection was found to be
      highest among middle-altitude women (0.386) as compared with high-altitude
      (0.370) women, whereas for the total population it is estimated to be 0.384. It
      was found that the Kinnaura of the Himalayan highland showing moderate index of
      total selection and relative contribution of the mortality component (Im) to the
      index of total selection is higher than the corresponding fertility component
      (If). The analysis of embryonic and post-natal mortality components shows that
      the post-natal mortality components are higher in comparison with the embryonic
      mortality components among highlanders and needs special intervention and health
      care. The present findings are compared with other Indian tribes as well as non
      tribes of the Himalayan region and other parts of the country. It reveals that
      this index among Kinnaura is moderate than the other population groups; among the
      Himalayan population, the highest was reported for Galong (It = 1.07) of
      Arunachal, whereas the lowest was reported from Ahom (It = 0.218) of Manipur. The
      correlation and regression analysis between total index of selection (It) and
      fertility (If) and mortality (Im) components for pooled data of populations of
      the Indian Himalayan states show that If and Im account for 21.6 and 29.1%
      variability, respectively. In Crow's total index of selection (It) along with
      strong association, which is significant at the 1% level, this indicates that
      mortality plays a greater role in natural selection in comparison with fertility
      among populations of the Indian Himalayas.

PMID- 21088719
TI  - A new recurring chromosome 13 abnormality in two older patients with de novo
      acute myeloid leukemia: An Indian experience.
AB  - We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype.
      short-term unstimulated bone marrow and peripheral blood lymphocyte culture
      showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with
      whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical
      abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here,
      we present two cases of elder male patients, which may constitute a distinct
      subtype.

PMID- 21088720
TI  - Ectrodactyly/split hand feet malformation.
AB  - Split-hand/split-foot malformation is a rare limb malformation with median clefts
      of the hands and feet and aplasia/hypoplasia of the phalanges, metacarpals and
      metatarsals. When present as an isolated anomaly, it is usually inherited as an
      autosomal dominant form. We report a case of autosomal recessive inheritance and
      discuss the antenatal diagnosis, genetic counseling and treatment for the
      malformation.

PMID- 21088721
TI  - Adenocarcinoma of the colon and rectum in the Kashmiri population.

PMID- 21088722
TI  - Crossword puzzles as a tool to enhance learning about anti-ulcer agents.
AB  - OBJECTIVE: To design, implement, and evaluate the use of crossword puzzles as a
      low-stakes educational tool for enhancing learning about anti-ulcer agents.
      DESIGN: Crossword puzzles were created using a free Internet resource and
      administered to students during 3 consecutive lectures covering the pharmacology
      and medicinal chemistry of anti-ulcer agents. Student perceptions of the
      crossword puzzle were examined using an 8-item survey instrument. ASSESSMENT:
      Over 90% of students indicated that crossword puzzles enhanced their learning,
      oriented them to the important topics, and served as good reviews of the lecture
      material. CONCLUSION: Students perceived that crossword puzzles enhanced their
      learning of anti-ulcer agents. Use of crossword puzzles provides a simple and
      creative way to incorporate active learning into pharmacy classroom instruction.

PMID- 21088723
TI  - A participation requirement to engage students in a pharmacokinetics course
      synchronously taught at a local and distant campus.
AB  - OBJECTIVE: To design, implement, and evaluate a strategy to actively engage
      doctor of pharmacy (PharmD) students at local and distant sites in a
      pharmacokinetics course. DESIGN: A Web-based system was designed that allowed
      second-year pharmacy students to choose whether to participate in a instructor
      led class discussion session by registering prior to or during the first 10
      minutes of each class. The instructor then used the program to randomly select
      students to respond to questions based on the assigned reading. Five percent of
      the overall course grade was based on class participation. ASSESSMENT: For each
      class session, an average of 85% of students at both the local and distant
      campuses registered for participation in class discussion and approximately 5%
      were called on to respond to questions. Student responses to course survey
      questions regarding the participation strategy were overwhelmingly positive, with
      75%-90% agreeing that the strategy more actively engaged them in classroom
      activities, resulting in improved learning. Student performance in all assessment
      categories was almost identical at the local and distant sites. CONCLUSIONS:
      Implementation of a participation strategy in a large course synchronously taught
      on 2 campuses is feasible and results in successful engagement of most students
      at both sites.

PMID- 21088724
TI  - Active-learning assignments to integrate basic science and clinical course
      material.
AB  - OBJECTIVE: To develop, implement, and evaluate active-learning exercises
      requiring the integration and application of pathophysiology, medicinal
      chemistry, pharmacology, and therapeutics knowledge of osteoarthritis and
      rheumatoid arthritis to formulate therapeutic recommendations for patients with
      musculoskeletal disorders. DESIGN: Two team-based case study exercises, one
      evaluating a patient with osteoarthritis and the second, a patient with
      rheumatoid arthritis, were developed, incorporating material and questions from
      pathophysiology, medicinal chemistry, pharmacology, and therapeutics. The
      learning assignments were implemented in a required pharmacotherapy module.
      ASSESSMENT: Student learning was evaluated using performance on the team-based
      case study exercises and on 2 examinations. A standard student course evaluation
      was used to assess students' impressions of the learning activity. The mean
      student grades for the osteoarthritis and rheumatoid arthritis activities were
      9.1 and 8.9, respectively, on a 10-point scale. The majority of students
      indicated that the learning exercises were more than adequate to excellent in
      helping students learn. CONCLUSION: The addition of active-learning activities
      was successful in teaching pharmacy students the knowledge needed to formulate
      therapeutic recommendations for patients with musculoskeletal disorders.

PMID- 21088725
TI  - Human simulators and standardized patients to teach difficult conversations to
      interprofessional health care teams.
AB  - OBJECTIVE: To design and implement a demonstration project to teach
      interprofessional teams how to recognize and engage in difficult conversations
      with patients. DESIGN: Interdisciplinary teams consisting of pharmacy students
      and residents, student nurses, and medical residents responded to preliminary
      questions regarding difficult conversations, listened to a brief discussion on
      difficult conversations; formed ad hoc teams and interacted with a standardized
      patient (mother) and a human simulator (child), discussing the infant's health
      issues, intimate partner violence, and suicidal thinking; and underwent
      debriefing. ASSESSMENT: Participants evaluated the learning methods positively
      and a majority demonstrated knowledge gains. The project team also learned
      lessons that will help better design future programs, including an emphasis on
      simulations over lecture and the importance of debriefing on student learning.
      Drawbacks included the major time commitment for design and implementation,
      sustainability, and the lack of resources to replicate the program for all
      students. CONCLUSION: Simulation is an effective technique to teach
      interprofessional teams how to engage in difficult conversations with patients.

PMID- 21088726
TI  - A process-oriented guided inquiry approach to teaching medicinal chemistry.
AB  - OBJECTIVE: To integrate process-oriented guided-inquiry learning (POGIL) team
      based activities into a 1-semester medicinal chemistry course for doctor of
      pharmacy (PharmD) students and determine the outcomes. DESIGN: Students in the
      fall 2007 section of the Medicinal Chemistry course were taught in a traditional
      teacher-centered manner, with the majority of class time spent on lectures and a
      few practice question sets. Students in the fall 2008 and fall 2009 sections of
      Medicinal Chemistry spent approximately 40% of class time in structured self
      selected teams where they worked through guided-inquiry exercises to supplement
      the lecture material. ASSESSMENT: The mean examination score of students in the
      guided-inquiry sections (fall 2008 and fall 2009) was almost 3 percentage points
      higher than that of students in the fall 2007 class (P < 0.05). Furthermore, the
      grade distribution shifted from a B-C centered distribution (fall 2007 class) to
      an A-B centered distribution (fall 2008 and fall 2009 classes). CONCLUSIONS: The
      inclusion of the POGIL style team-based learning exercises improved grade
      outcomes for the students, encouraged active engagement with the material during
      class time, provided immediate feedback to the instructor regarding student
      knowledge deficiencies, and created a classroom environment that was well
      received by students.

PMID- 21088727
TI  - Professional and educational initiatives, supports, and opportunities for
      advanced training in public health.
AB  - The United States is facing a public health workforce shortage and pharmacists
      have the opportunity and obligation to address this challenge in health care.
      There have been initiatives and supports from within and beyond the profession
      for the pharmacist's role in public health. This article identifies existing
      professional and educational initiatives for the pharmacist's expanded role in
      public health, as well as postgraduate and other advanced educational
      opportunities in public health. Recommendations also are provided on how to
      further engage pharmacists in public health activities to alleviate the public
      health workforce challenge.

PMID- 21088728
TI  - Development of a center for teaching excellence.
AB  - This article describes the development, implementation, and assessment of a
      Center for Teaching Excellence at Midwestern University Chicago College of
      Pharmacy. The purpose of the Center was to create a systematic framework to
      promote, enhance, and assess the scholarship of teaching and learning. Assessment
      of the Center's activities suggests a positive impact on the teaching abilities
      of faculty. This report is intended to offer other schools or colleges of
      pharmacy considerations for center development.

PMID- 21088729
TI  - The status of US multi-campus colleges and schools of pharmacy.
AB  - OBJECTIVE: To assess the current status of multi-campus colleges and schools of
      pharmacy within the United States. METHODS: Data on multi-campus programs,
      technology, communication, and opinions regarding benefits and challenges were
      collected from Web sites, e-mail, and phone interviews from all colleges and
      schools of pharmacy with students in class on more than 1 campus. RESULTS: Twenty
      schools and colleges of pharmacy (18 public and 2 private) had multi-campus
      programs; 16 ran parallel campuses and 4 ran sequential campuses. Most programs
      used synchronous delivery of classes. The most frequently reported reasons for
      establishing the multi-campus program were to have access to a hospital and/or
      medical campus and clinical resources located away from the main campus and to
      increase class size. Effectiveness of distance education technology was most
      often sited as a challenge. CONCLUSION: About 20% of colleges and schools of
      pharmacy have multi-campus programs most often to facilitate access to clinical
      resources and to increase class size. These programs expand learning
      opportunities and face challenges related to technology, resources, and
      communication.

PMID- 21088730
TI  - PharmD and needs-based education: an alternate view.

PMID- 21088731
TI  - Overdraft protection for experiential education.

PMID- 21088732
TI  - The status of PhD education in economic, social, and administrative sciences
      between 2005 and 2008.
AB  - OBJECTIVES: To describe the funding, education, enrollment, and graduation
      patterns from economic, social, and administrative sciences PhD programs in
      colleges and schools of pharmacy in the United States. METHODS: Economic, social,
      and administrative sciences PhD programs were identified from the American
      Association of Colleges of Pharmacy (AACP) Web site. A 41-item online survey
      instrument was sent to the director of graduate studies of each identified
      program. Only programs offering a PhD degree were included in the study. RESULTS:
      Of the 26 programs surveyed, 20 (77%) provided useable responses to the survey
      instrument. Approximately 91% of PhD programs guarantee funding to incoming
      students with an average commitment of 2.9 years. On average, students were paid
      a stipend of $18,000 per year for commitments to research and teaching
      assistantships, each averaging approximately 2 years in length. Programs admitted
      an average of 3.5 students per year and graduated approximately 85% of entering
      students. The majority of students are non-US citizens and accept positions in
      either academic or industrial positions after graduation. CONCLUSIONS: Most
      economic, social, and administrative sciences PhD programs guarantee funding to
      incoming PhD candidates. Programs offering funding packages significantly below
      the average may be at a competitive disadvantage. It is unclear whether the
      number of students graduating from PhD programs is adequate to fulfill academic
      and industrial needs.

PMID- 21088733
TI  - Impact of online lecture-capture on student outcomes in a therapeutics course.
AB  - OBJECTIVES: To examine the correlation between students accessing recorded
      lecture files (audio and slides) online and course grades and class attendance.
      METHODS: Second professional year (of 6-year program) students in a therapeutics
      course had access to recorded online lectures for 72 hours following live
      lectures. The number and duration of lecture accessions were compared to final
      course grades and class attendance. Course grades were compared to those of a
      historical control group. At the end of the semester, students completed a brief
      survey instrument regarding their use and perceptions of online lectures.
      RESULTS: No correlation was found between final course grades and the number of
      lecture accessions (r = 0.0014) or total number of minutes lectures were viewed
      (r = 0.033), nor between class attendance and minutes viewed (r = 0.2158).
      Students with access to recorded lectures outperformed the historical control
      group on the final examination (p < 0.002). Seventy-two percent of students
      reported no influence of online files on class attendance. CONCLUSIONS: Posting
      lectures online did not affect student outcomes, but students did score higher on
      the final examination.

PMID- 21088734
TI  - An electronic NAPLEX review program for longitudinal assessment of pharmacy
      students' knowledge.
AB  - OBJECTIVES: To track pharmacy student knowledge over time using a proprietary
      software program in an accelerated program for curricular assessment. METHODS:
      All students were required to complete a computerized comprehensive diagnostic
      examination 3 times during the doctor of pharmacy (PharmD) program: at the
      beginning of the second year, and near the end of the second and third years. The
      examination was comprised of 100 questions in 3 content areas: pharmacotherapy,
      preparation and dispensing of medications, and providing health care information.
      Within-subject differences in mean area and total percent scores were compared.
      RESULTS: Based on 123 students' data, mean scores for pharmacotherapy and total
      percent scores for examination 1 were significantly different from examinations 2
      and 3. CONCLUSION: The computer-based comprehensive diagnostic examination shows
      promise for use as a component of a comprehensive assessment plan.

PMID- 21088735
TI  - Reinforcing cultural competency concepts during introductory pharmacy practice
      experiences.
AB  - OBJECTIVES: To incorporate cultural competency concepts into various introductory
      pharmacy practice experiences (IPPE) at the University of Missouri - Kansas City,
      School of Pharmacy. DESIGN: A 6-week series, titled "Becoming a Culturally
      Competent Provider" was developed to provide IPPE students with the opportunity
      to apply theory regarding cultural competency in a clinical context. ASSESSMENT:
      Pre- and post-intervention attitude survey instruments were administered to 25
      students in the spring semester of 2009. Several activities within the series
      were associated with reflection exercises. Student presentations were evaluated
      and formal feedback was provided by faculty members. A course evaluation was
      administered to evaluate the series and determine areas of improvement.
      CONCLUSION: A special series on cultural competency resulted in positive changes
      in students' attitudes, highlighting the importance of reinforcing cultural
      competency concepts during IPPEs.

PMID- 21088736
TI  - A week-long diabetes simulation for pharmacy students.
AB  - OBJECTIVE: To assess students' attitudes and confidence about type 2 diabetes
      mellitus and diabetes self-management education before and after participation in
      Living With Diabetes Week simulation. DESIGN: Third-year pharmacy students took
      part in diabetes lectures, interactive laboratory sessions, and a week-long
      simulation of life as a patient with diabetes in the Clinical Assessment course.
      Pre-/postintervention survey instruments and experimental and control group
      comparisons were completed assessing attitudes and confidence relating to
      knowledge about diabetes. ASSESSMENT: The understanding that diabetes has a
      psychosocial impact, patient autonomy is necessary, and the seriousness of the
      disease increased. Students' confidence in their diabetes self-management
      education skills also increased. CONCLUSION: The Living With Diabetes Week
      simulation changed pharmacy students' attitudes toward patients with diabetes and
      increased confidence in diabetes education skills.

PMID- 21088737
TI  - A course introducing the principles of pharmaceutical care.
AB  - OBJECTIVES: To develop, implement, and assess a course that introduces students
      to the process and application of pharmaceutical care. DESIGN: The course was
      offered to students in the third semester of the PharmD curriculum. The course's
      ability outcomes were to integrate and apply scientific and therapeutic knowledge
      in the delivery of evidence-based pharmaceutical care, and to develop the skills
      of a professional, lifelong learner. ASSESSMENT: The students successfully
      applied the information learned in this course to the practice of pharmaceutical
      care. The 3 components of the course that appeared to be the most challenging
      were identifying drug-therapy problems, creating compound goals, and creating a
      care plan. CONCLUSION: This course was effective in meeting ability-based
      outcomes. The assessment data helped the instructors determine what changes
      should be made to increase the course's success when it is offered again.

PMID- 21088738
TI  - Vital sign monitoring using human patient simulators at pharmacy schools in
      Japan.
AB  - OBJECTIVE: To develop, implement, and assess an experience-based education
      program using human patient simulators to instruct pharmacy students in
      monitoring vital signs to identify drug treatment effects and adverse events.
      DESIGN: Medical emergency care programs using human patient simulators were
      prepared and facilitated practical clinical training in resuscitation, which
      required selecting drugs while monitoring changes in blood pressure, pulse, and
      arterial blood oxygen saturation. Training encompassed the monitoring of routes
      of drug administration, drawing of simulated blood, vital-sign monitoring based
      on a pharmaceutical universal training model, vital-sign monitoring devices and
      simulators, and medical emergency education using biological simulators.
      ASSESSMENT: Before and after bedside training, students were asked to complete a
      questionnaire to assess their understanding of vital sign monitoring and
      emergency care. Students successfully learned how to monitor routes of drug
      administration, vital signs, and pathological conditions. There was a significant
      increase in students' recognition of the importance of vital-sign monitoring.
      CONCLUSION: Experienced-based training using patient simulators successfully
      prepared pharmacy students to monitor vitals signs and identify drug treatment
      effects and adverse events.

PMID- 21088739
TI  - Car keys, house keys, Easter eggs, and curricula.

PMID- 21088740
TI  - A case study in terminology: the FIP Pharmacy Education Taskforce.

PMID- 21088741
TI  - Gastro-hep news.

PMID- 21088742
TI  - The Role of Serologic and Genetic Testing in IBD: Now and Looking Ahead.

PMID- 21088743
TI  - The water immersion technique for colonoscopy insertion.

PMID- 21088744
TI  - Aquaretics in the treatment of ascites.

PMID- 21088745
TI  - Emerging Medical Therapies for the Treatment of GERD.

PMID- 21088746
TI  - Evaluation and management of hepatitis B in pregnancy: a survey of current
      practices.
AB  - BACKGROUND: Optimal management of hepatitis B (HBV) during pregnancy is unclear.
      Safety and efficacy data of antiviral therapy are limited. We assessed the
      practice patterns of hepatologists, gastroenterologists, and other physicians for
      evaluating and managing pregnant patients with HBV as well as the variation of
      these practice patterns by primary specialty and practice description. METHODS:
      An 18-question electronic survey was sent to physicians with a special interest
      in liver disease addressing the evaluation and management of HBV during
      pregnancy. RESULTS: A total of 226 physicians responded, of whom 68.5%
      characterized their primary specialty as hepatology, 26.5% as gastroenterology,
      and 4.9% as other; 62.4% were academic-based physicians, and 37.6% were community
      based physicians. The average years in practice were 13.3. Initiation of
      antiviral therapy during pregnancy was supported by 51.8% of respondents. Of
      those against therapy initiation, 60.4% cited a lack of clear recommendations,
      32.1% cited safety concerns, and 7.5% cited a lack of efficacy. For patients on
      antivirals who desired to become pregnant, 74.8% of respondents would continue
      antiviral therapy. The most common antiviral used in pregnancy was lamivudine
      (72.1%). HBV vaccination and HBV immunoglobulin for infants born to mothers with
      HBV were recommended by 98.7% of respondents; 57.5% would also recommend
      breastfeeding. If antivirals were being used, only 30.5% of respondents would
      still recommend breastfeeding. More hepatologists were "very comfortable"
      (P=.032) managing these patients compared to nonhepatologists. CONCLUSIONS: There
      is significant heterogeneity in the management of pregnant patients with HBV
      regardless of primary specialty or practice description. This variability likely
      reflects a lack of data and specific guidelines. Further research and more
      specific guidelines are needed.

PMID- 21088747
TI  - Ingested foreign bodies in a patient with pica.

PMID- 21088748
TI  - Clinical and endoscopic aspects of foreign body ingestion.

PMID- 21088749
TI  - Efficacy and complications of surgery for Crohn's disease.
AB  - Patients with Crohn's disease commonly undergo surgery during their lifetime.
      Indications for surgical intervention include obstruction, intra-abdominal or
      perianal abscess, enterocutaneous fistulas, and complex perianal disease. As
      medical therapies continue to improve, it is important that surgical therapies
      are chosen carefully. This is particularly important in the treatment of perianal
      fistulas; combined surgical and medical therapy offer the best chance for
      success. In the treatment of small-bowel disease, bowel preservation is key. For
      the repair of short strictures, endoscopic dilatation is the preferred method
      when accessible; strictureplasty has been shown to be safe and effective for
      increasingly longer segments of disease. Intra-abdominal abscesses should be
      drained percutaneously, if possible. In the presence of colonic disease,
      segmental resection is recommended. Unfortunately, refractory disease still
      frequently requires complete proctectomy and permanent diversion.

PMID- 21088750
TI  - Pericardial approach for cardiac therapies: old practice with new ideas.
AB  - Treatment of cardiac disease via the epicardium fell under the domain of cardiac
      surgery due to the need for an open thoracotomy. Since an open thoracotomy is
      invasive in nature and has the potential for complications, a minimally invasive
      and percutaneous approach would be more attractive for suitable patients. The
      recent success of epicardial ablation of refractory arrhythmia via the
      percutaneous pericardial approach has increased the potential for delivery of
      epicardial therapies. Epicardial ablation has increased the success and safety
      since anti-coagulation and transseptal catheterization for left atrial
      arrhythmias is not required. The pericardial space has also been used to deliver
      therapy for several cardiac diseases. There are reports on successful delivery of
      drugs and their efficacy. Even though there was a wide range of efficacies
      reported in those studies, the reported complication rates are strikingly low,
      which suggests that direct delivery of drugs to the epicardium via the
      pericardial space is safe. Furthermore, recent animal studies have supported the
      feasibility of epicardial delivery of biological agents, including genes, cells,
      and even genetically engineered tissue for therapeutic purposes. In conclusion,
      percutaneous pericardial cannulation of closed pericardial space can play a
      significant role in providing non-surgical therapy for cardiovascular diseases.
      However, it requires skills and operator experiences. Therefore, there is need to
      further develop new tools, safer techniques, and effective procedure environment
      before generalizing this procedure.

PMID- 21088751
TI  - Kawasaki disease and hyponatremia.

PMID- 21088752
TI  - High Lipoprotein(a) Levels are Associated With Long-Term Adverse Outcomes in
      Acute Myocardial Infarction Patients in High Killip Classes.
AB  - BACKGROUND AND OBJECTIVES: An elevated concentration of lipoprotein(a) {Lp(a)} is
      associated with an increased prevalence and increased severity of coronary artery
      disease. However, the relationship between Lp(a) levels and outcomes after acute
      myocardial infarction (AMI) is unclear. SUBJECTS AND METHODS: Between October
      2005 and June 2007, we measured serum Lp(a) levels in 832 consecutive AMI
      patients (age, 62.8+/-12.4 years, 600 men) on admission. They were divided into
      tertiles according to their serum Lp(a) levels {Tertile 1 (n=276), Lp(a)<13.8
      mg/dL; Tertile 2 (n=279), Lp(a)=13.8-30.6 mg/dL; Tertile 3 (n=277), Lp(a)>30.6
      mg/dL}. RESULTS: There were no differences in baseline clinical characteristics
      among Tertiles 1, 2, and 3, except for proportions of Killip class III-IV
      patients (5.8% vs. 10.0% vs. 18.8%, respectively, p<0.001). There were
      significant differences in left ventricular ejection fractions (57.3+/-11.4% vs.
      55.9+/-12.3% vs. 53.1+/-13.1%, p<0.001). Among the laboratory findings, there
      were significant differences in total cholesterol (173.3+/-37.2 vs. 183.5+/-38.9
      vs. 185.3+/-43.8 mg/dL, p=0.001), low density lipoprotein-cholesterol (111.3+/
      34.3 vs. 122.9+/-34.7 vs. 123.3+/-39.4 mg/dL, p<0.001), apolipoprotein B (92.8+/
      25.4 vs. 100.8+/-26.0 vs. 101.9+/-28.8 mg/dL, p<0.001), and amino-terminal pro
      brain natriuretic peptide levels (1805.2+/-4343.3 vs. 2607.9+/-5216.3 vs.
      3981.5+/-7689.7 pg/mL, p<0.001). After adjusting for multiple variables in the
      high Killip class (III-IV) subgroup, the risk estimate for major adverse
      cardiovascular events (MACE) at 1-year follow-up was significantly higher in
      Tertile 3 than in Tertiles 1 or 2 (hazard ratio 6.723, 95% confidence interval
      1.037-43.593, p=0.046). CONCLUSION: In patients in high Killip classes, high
      serum levels of Lp(a) were significantly associated with long-term adverse
      outcomes after AMI.

PMID- 21088753
TI  - Electrocardiography patterns and the role of the electrocardiography score for
      risk stratification in acute pulmonary embolism.
AB  - BACKGROUND AND OBJECTIVES: Data on the usefulness of a combination of different
      electrocardiography (ECG) abnormalities in risk stratification of patients with
      acute pulmonary embolism (PE) are limited. We thus investigated 12-lead ECG
      patterns in acute PE to evaluate the role of the ECG score in risk stratification
      of patients with acute PE. SUBJECTS AND METHODS: One hundred twenty-five
      consecutive patients (63+/-14 years, 56 men) with acute PE who were admitted to
      Kyungpook National University Hospital between November 2001 and January 2008
      were included. We analyzed ECG patterns and calculated the ECG score in all
      patients. We evaluated right ventricular systolic pressure (RVSP) (n=75) and RV
      hypokinesia (n=80) using echocardiography for risk stratification of acute PE
      patients. RESULTS: Among several ECG findings, sinus tachycardia and inverted T
      waves in V(1-4) (39%) were observed most frequently. The mean ECG score and RVSP
      were 7.36+/-6.32 and 49+/-21 mmHg, respectively. The ECG score correlated with
      RVSP (r=0.277, p=0.016). The patients were divided into two groups {high ECG
      score group (n=38): ECG score >12 and low ECG-score group (n=87): ECG score <=12}
      based on the ECG score, with the maximum area under the curve. RV hypokinesia was
      observed more frequently in the high ECG-score group than in the low ECG-score
      group (p=0.006). Multivariate analysis revealed that a high ECG score was an
      independent predictor of high RVSP and RV hypokinesia. CONCLUSION: Sinus
      tachycardia and inverted T waves in V(1-4) were commonly observed in acute PE.
      Moreover, the ECG score is a useful tool in risk stratification of patients with
      acute PE.

PMID- 21088754
TI  - Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion in
      kawasaki disease.
AB  - BACKGROUND AND OBJECTIVES: The pathogenesis of hyponatremia (serum sodium <135
      mEq/L) in Kawasaki disease (KD) remains unclear. We investigated the clinical
      significance of hyponatremia, and the role of interleukin (IL)-6 and IL-1beta in
      the development of hyponatremia and syndrome of inappropriate antidiuretic
      hormone secretion (SIADH) in KD. SUBJECTS AND METHODS: Fifty KD patients were
      prospectively enrolled and analyzed for clinical and laboratory variables
      according to the presence of hyponatremia or SIADH. RESULTS: Thirteen KD patients
      (26%) had hyponatremia and 6 of these had SIADH. In patients with hyponatremia,
      the percentage of neutrophils (% neutrophils), C-reactive protein (CRP), and N
      terminal pro-brain natriuretic peptide (NT-proBNP) were higher than in those
      without hyponatremia, while serum triiodothyronine (T3) and albumin were lower.
      Patients with hyponatremia had a higher incidence of intravenous immunoglobulin
      resistance but this was not statistically significant. No differences existed
      between patients with and without SIADH with regard to clinical or laboratory
      variables and the incidence of IVIG-resistance. Serum sodium inversely correlated
      with % neutrophils, CRP, and NT-proBNP, and positively correlated with T3 and
      albumin. Serum IL-6 and IL-1beta levels increased in KD patients and were higher
      in patients with hyponatremia. Plasma antidiuretic hormone increased in patients
      with SIADH, which tended to positively correlate with IL-6 and IL-1beta levels.
      CONCLUSION: Hyponatremia occurs in KD patients with severe inflammation, while
      increased IL-6 and IL-1beta may activate ADH secretion, leading to SIADH and
      hyponatremia in KD.

PMID- 21088755
TI  - Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker,
      on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential
      Hypertension.
AB  - BACKGROUND AND OBJECTIVES: Efonidipine hydrochloride, an L- and T-type dual
      calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in
      addition to a blood pressure (BP)-lowering effect. The aim of this study was to
      determine the effect of efonidipine on HR and BP in patients with mild-to
      moderate hypertension. SUBJECTS AND METHODS: In a multi-center, prospective, open
      labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate
      hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout,
      eligible patients were treated with efonidipine (40 mg once daily for 12 weeks).
      The primary end point was the change in HR from baseline to week 12. The
      secondary end-point included the change in trough sitting BP and 24-hour mean BP
      between baseline and week 12. Laboratory and clinical adverse events were
      monitored at each study visit (4, 8, and 12 weeks). RESULTS: Fifty-two patients
      were included in the intention-to-treat analysis. After 12 weeks of treatment
      with efonidipine, the resting HR decreased significantly from baseline to week 12
      {from 81.5+/-5.3 to 71.8+/-9.9 beats/minute (difference, -9.9+/-9.0
      beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP)
      and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6+/
      8.2 to 132.9+/-13.5 mmHg, p<0.0001; SiDBP: from 96.9+/-5.4 to 88.3+/-8.6 mmHg,
      p<0.0001, 24-hour mean systolic BP: from 140.4+/-13.5 to 133.8+/-11.6 mmHg,
      p<0.0001; 24-hour mean diastolic BP: from 91.7+/-8.7 to 87.5+/-9.5 mmHg,
      p<0.0001). CONCLUSION: Efonidipine was effective in controlling both HR and BP in
      patients with mild-to-moderate hypertension.

PMID- 21088756
TI  - Alagebrium chloride, a novel advanced glycation end-product cross linkage
      breaker, inhibits neointimal proliferation in a diabetic rat carotid balloon
      injury model.
AB  - BACKGROUND AND OBJECTIVES: Vascular perturbation induced by advanced glycation
      end-products (AGEs) leads to progression of atherosclerosis, plaque instability,
      and vascular inflammation, which results in a higher risk of neointimal
      proliferation. Here we investigated the inhibitory effect of alagebrium chloride
      (ALT-711), a breaker of AGE-based cross links, on neointimal proliferation in a
      carotid artery balloon injury model in diabetic rats induced by streptozotocin
      (STZ). MATERIALS AND METHODS: Rat aortic vascular smooth muscle cells (RASMCs)
      were treated with 1-100 uM of alagebrium added 24 hours before the addition of
      AGEs. This in vivo study was done using 8-week-old male rats that were injected
      intraperitoneally with 80 mg/kg STZ. Sixteen weeks later, the diabetic rats were
      treated with 10 mg/kg alagebrium for 4 weeks, after which carotid artery balloon
      injury was induced. After 4 weeks, the animals were sacrificed for histological
      analysis. RESULTS: Proliferation of RASMCs was significantly inhibited in
      alagebrium-treated cells. Alagebrium dose-dependently inhibited AGE-mediated
      formation of reactive oxygen species (ROS), extracellular signal-regulated kinase
      phosphorylation, and cyclooxygenase-2 expression. The cellular mechanisms of AGE
      induced connective tissue and extracellular matrix expression were decreased in
      the alagebrium-treated group. This in vivo study shows that expression of AGE
      receptors and neointima hyperplasia are significantly suppressed in balloon
      injured rats treated with alagebrium. CONCLUSION: Alagebrium treatment in
      diabetic rats significantly inhibits neointimal hyperplasia after carotid balloon
      injury due to its inhibition of intracellular ROS synthesis, which results in
      inhibition of RASMCs proliferation.

PMID- 21088757
TI  - Successful percutaneous coronary intervention for acute coronary syndrome in a
      patient with severe hemophilia a.
AB  - Patients with hemophilia generally have a reduced frequency of coronary artery
      disease compared to the general population. As advances in the management of
      hemophilia have increased their life expectancy, the prevalence of coronary
      artery disease also has increased. However, there are no standard treatment
      guidelines for coronary artery disease in patients with hemophilia, especially in
      the field of coronary intervention. We report the case of a patient with severe
      hemophilia A who presented with acute coronary syndrome and was successfully
      treated with percutaneous coronary intervention.

PMID- 21088758
TI  - Three cases of non-surgical treatment of stent loss during percutaneous coronary
      intervention.
AB  - Percutaneous coronary intervention with stenting is widely used for ischemic
      heart disease. Because stent loss, which occurs rarely during the procedure,
      might have dire consequences, such as bleeding, stent embolism, acute myocardial
      infarction, emergency coronary artery bypass graft, and death, appropriate
      treatment is needed as soon as stent loss occurs. We report three cases of stent
      loss which were successfully treated with three different non-surgical methods.

PMID- 21088759
TI  - Acute Myocardial Infarction by Right Coronary Artery Occlusion Presenting as
      Precordial ST Elevation on Electrocardiography.
AB  - It is rare to observe ST-segment elevation in only the anterior leads and not the
      inferior leads during right coronary artery occlusion. We describe a case with
      acute myocardial infarction (MI) by right coronary artery occlusion who developed
      ST-segment elevation only in the precordial leads V1 to V3.

PMID- 21088760
TI  - Constrictive Pericarditis Accompanied by Swine-Origin Influenza A (H1N1)
      Infection.
AB  - Swine-origin influenza A (H1N1) is caused by a new strain of the influenza virus.
      The disease has spread rapidly and was declared a pandemic in April, 2009. So
      far, however, there is a scarcity of information regarding the complications of
      swine influenza. A report of the disease in the winter of 2009 in the Southern
      Hemisphere found that the most common manifestations of influenza A virus
      infection are upper respiratory tract infection and pneumonia. Although there may
      be an association between fulminant myocarditis and Swine influenza,
      cardiovascular complications resulting from swine Influenza A infection are
      exceedingly rare. We report a case of acute constrictive pericarditis in a
      healthy subject infected by the swine-origin influenza A (H1N1) virus.

PMID- 21088761
TI  - Multiscale molecular dynamics using the matched interface and boundary method.
AB  - The Poisson-Boltzmann (PB) equation is an established multiscale model for
      electrostatic analysis of biomolecules and other dielectric systems. PB based
      molecular dynamics (MD) approach has a potential to tackle large biological
      systems. Obstacles that hinder the current development of PB based MD methods are
      concerns in accuracy, stability, efficiency and reliability. The presence of
      complex solvent-solute interface, geometric singularities and charge
      singularities leads to challenges in the numerical solution of the PB equation
      and electrostatic force evaluation in PB based MD methods. Recently, the matched
      interface and boundary (MIB) method has been utilized to develop the first second
      order accurate PB solver that is numerically stable in dealing with discontinuous
      dielectric coefficients, complex geometric singularities and singular source
      charges. The present work develops the PB based MD approach using the MIB method.
      New formulation of electrostatic forces is derived to allow the use of sharp
      molecular surfaces. Accurate reaction field forces are obtained by directly
      differentiating the electrostatic potential. Dielectric boundary forces are
      evaluated at the solvent-solute interface using an accurate Cartesian-grid
      surface integration method. The electrostatic forces located at reentrant
      surfaces are appropriately assigned to related atoms. Extensive numerical tests
      are carried out to validate the accuracy and stability of the present
      electrostatic force calculation. The new PB based MD method is implemented in
      conjunction with the AMBER package. MIB based MD simulations of biomolecules are
      demonstrated via a few example systems.

PMID- 21088762
TI  - Amine, Melamine, and Amide N-Halamines as Antimicrobial Additives for Polymers.
AB  - N-chloro-2,2,6,6-tetramethyl-4-piperidinol laurate (Cl-TMPL) was prepared by
      reacting 2,2,6,6-tetramethyl-4-piperidinol hydrochloride (TMP.HCl) with lauroyl
      chloride, followed by chlorination with sodium dichloroisocyanurate. The chemical
      structure of Cl-TMPL was characterized with FT-IR, NMR, DSC, and TGA analyses.
      The antimicrobial performance of Cl-TMPL against Gram-positive and Gram-negative
      bacteria was compared with 1-chloro-3-dodecyl-5,5-dimethylhydantoin (Cl-DDMH), a
      amide N-halamine, and chloro-2,4-diamino-6-dodecyl-1,3,5-triazine (Cl-DADT), a
      melamine (imino) N-halamine. The three classes of N-halamines were used as
      additives for polyurethane (PU). Visible light transparency data indicated that
      up to 6% of Cl-DDMH or Cl-DADT could be compatibly mixed with PU, but Cl-TMPL had
      low compatibility with PU at higher than 2% of Cl-TMPL. With the same additive
      content, Cl-DDMH and Cl-DADT provided more powerful antimicrobial and biofilm
      controlling effects than Cl-TMPL. In stability studies, however, PU samples with
      Cl-TMPL released the lowest amount of active chlorine into the immersing
      solution, suggesting the highest stability of the antimicrobial and biofilm
      controlling efficacy.

PMID- 21088763
TI  - Few constraints limit the design of quinone methide-oligonucleotide self-adducts
      for directing DNA alkylation.
AB  - Nucleotide sequences minimally containing adenosine, cytosine or guanosine are
      sufficient to form intrastrand oligonucleotide quinone methide self-adducts
      reversibly for subsequent alkylation of complementary DNA. The general lack of
      sequence restrictions should now allow for alkylation of most any target of
      interest although reaction is most efficient when the self-adducts contain
      guanine residues and do not form hairpin structures.

PMID- 21088764
TI  - Water-solubilisation and bio-conjugation of a red-emitting BODIPY marker.
AB  - The synthesis and preliminary bio-conjugation studies of a novel water-soluble
      red-emitting di-styryl BODIPY dye are disclosed. Aggregation behaviour of this
      compound under physiological conditions was suppressed by specific introduction
      of a di-sulfonated peptide-based linker at the meso phenyl substituent,
      sultonated styryl arms and short polyethyleneglycol chains at the boron center.
      Thus, a good quantum yield of 22% in PBS for this red-emitting BODIPY was
      obtained. Introduction of an activated ester function enabled successful bio
      conjugation to monoclonal antibodies and proteins.

PMID- 21088766
TI  - Benzoylureas as removable cis amide inducers: synthesis of cyclic amides via ring
      closing metathesis (RCM).
AB  - Rapid and high yielding synthesis of medium ring lactams was made possible
      through the use of a benzoylurea auxiliary that serves to stabilize a cisoid
      amide conformation, facilitating cyclization. The auxiliary is released after
      activation under the mild conditions required to deprotect a primary amine, such
      as acidolysis of a Boc group in the examples given here. This methodology is a
      promising tool for the synthesis of medium ring lactams, macrocyclic natural
      products and peptides.

PMID- 21088765
TI  - High-throughput tracking of single yeast cells in a microfluidic imaging matrix.
AB  - Time-lapse live cell imaging is a powerful tool for studying signaling network
      dynamics and complexity and is uniquely suited to single cell studies of response
      dynamics, noise, and heritable differences. Although conventional imaging formats
      have the temporal and spatial resolution needed for such studies, they do not
      provide the simultaneous advantages of cell tracking, experimental throughput,
      and precise chemical control. This is particularly problematic for system-level
      studies using non-adherent model organisms such as yeast, where the motion of
      cells complicates tracking and where large-scale analysis under a variety of
      genetic and chemical perturbations is desired. We present here a high-throughput
      microfluidic imaging system capable of tracking single cells over multiple
      generations in 128 simultaneous experiments with programmable and precise
      chemical control. High-resolution imaging and robust cell tracking are achieved
      through immobilization of yeast cells using a combination of mechanical clamping
      and polymerization in an agarose gel. The channel and valve architecture of our
      device allows for the formation of a matrix of 128 integrated agarose gel pads,
      each allowing for an independent imaging experiment with fully programmable
      medium exchange via diffusion. We demonstrate our system in the combinatorial and
      quantitative analysis of the yeast pheromone signaling response across 8
      genotypes and 16 conditions, and show that lineage-dependent effects contribute
      to observed variability at stimulation conditions near the critical threshold for
      cellular decision making.

PMID- 21088767
TI  - Synchrotron FTIR analysis of drug treated ovarian A2780 cells: an ability to
      differentiate cell response to different drugs?
AB  - Recently a new di-gold(I) organometallic complex [1,3-(Ph(3)PAu)(2)-C(6)H(4)]
      (KF0101) has been synthesised and found to exhibit cytotoxic activity in vitro.
      Subsequently it has been demonstrated that KF0101 shows little or no cross
      resistance against a number of the cisplatin resistant ovarian cancer cell lines
      in vitro suggesting a different mode of action for the drug. In this study,
      syncrotron radiation infrared microspectroscopy (SR-IRMS) has been used on drug
      treated single A2780 cells in order to determine if this different mode of action
      can be identified spectroscopically. The aim of the study was to establish: (i)
      if single cell SR-IRMS could be used to give insight into the cellular response
      on treatment with different cytotoxic agents relative to non-treated cells
      (control) and (ii) that if the cytotoxic drugs elicit a different biochemical
      response these responses could be distinguished from each other. The most
      striking features obtained after Principal Components Analysis (PCA) of Resonant
      Mie Scattering (RMieS) corrected single cell spectra of drug treated ovarian
      A2780 cells are: (i) The spectra obtained for the control are quite heterogeneous
      and several hundred spectra are required to adequately define the nature of the
      control; (ii) after drug treatment at the IC50 level for 24 h with cisplatin,
      KF0101, methotrexate, paclitaxel or 5-fluorouracil the cell spectra, as
      represented on a PCA scores plot, generally concentrate in certain well defined
      areas of the control, there are however a small number of spectra that fall
      outside of the area defined by the control; and (iii) a differentiation between
      cell spectra obtained on treatment with different drugs is observed which fits
      well with different in vitro cell culture behaviour and a flow cytometry cell
      cycle analysis of the control and drug treated cells. Inspection of the loading
      plots shows that PC1 is essentially the same for all plots and reflects changes
      in cell biochemistry related to the cell cycle. PC2, however, on comparison of
      the control versus cisplatin or cisplatin versus KF0101 is indicative of
      differences induced by drug treatment and has been termed as cell cycle-plus
      behaviour. These data are shown to be consistent with that obtained using bench
      top IRMS by averaging a number of single cell spectra and carrying out a PCA, but
      SR-IRMS offers more insight into how the drug is affecting the cell population.
      More importantly, this approach enables the influence of the cell cycle on both
      the control and drug treated samples to be taken into consideration when
      evaluating the drug-cell interaction.

PMID- 21088768
TI  - Gold-black micropillar electrodes for microfluidic ELISA of bone metabolic
      markers.
AB  - Modification with gold black considerably increased the detection current of
      protruding micropillar electrodes in microfluidic electrochemical enzyme-linked
      immunosorbent assay (ELISA).

PMID- 21088769
TI  - First total synthesis of antrocamphin A and its analogs as anti-inflammatory and
      anti-platelet aggregation agents.
AB  - Naturally occurring antrocamphin A (1) is a potent anti-inflammatory compound
      from the edible fungus Antrodia camphorata (Taiwanofungus camphoratus), whose
      wild fruiting body is used as a valuable folk medicine in Taiwan. This study is
      the first total synthesis of antrocamphin A (1) and its analogs. Their inhibition
      ability on NO release, superoxide anion generation, elastase release and platelet
      aggregation are reported herein.

PMID- 21088770
TI  - Asymmetrically substituted calix[4]pyrrole with chiral substituents.
AB  - We have prepared first calix[4]pyrrole containing unprotected carbohydrate moiety
      directly linked to meso-position of oligopyrrole by stable "C-glycosidic" bond.
      Basic examination of its superassembly capability is presented.

PMID- 21088771
TI  - Enantioselective organocatalytic domino Michael-acetalization-Henry reactions of
      2-hydroxynitrostyrene and aldehyde for the synthesis of tetrahydro-6H
      benzo[c]chromenones.
AB  - Asymmetric domino Michael-acetalization reactions of 2-hydroxynitrostyrene and
      aldehydes "on water" followed by oxidation providing the cis-3,4-disubstituted
      dihydrocoumarins with excellent enantioselectivities (up to >99% ee). The variant
      with glutaraldehyde underwent a highly stereoselective domino Michael
      acetalization-Henry reaction to afford the tetrahydro-6H-benzo[c]chromen-6-ones
      after the subsequent oxidation.

PMID- 21088772
TI  - The recent synthesis and application of silicon-stereogenic silanes: a renewed
      and significant challenge in asymmetric synthesis.
AB  - The synthesis of silicon-stereogenic silanes is undoubtedly one of the most
      intriguing and challenging aspects in organic chemistry and organosilicon
      chemistry and is neglected by chemists to some extent. This critical review will
      focus on the recent exciting advances in the synthesis of silicon-stereogenic
      silane and outline the application of these chiral silanes in asymmetric
      synthesis (89 references).

PMID- 21088773
TI  - Nanoparticle-based mass spectrometry for the analysis of biomolecules.
AB  - Nanoparticles (NPs) are useful as matrixes for the analyses of several types of
      biomolecules (including aminothiols, peptides, and proteins) and for mass
      spectrometric imaging through surface-assisted laser desorption/ionization mass
      spectrometry (SALDI-MS), mainly because of their large surface area, strong
      absorption in the ultraviolet-near-infrared region, and ready functionalization.
      Metallic NPs, metal oxide NPs, and semiconductor quantum dots, unmodified or
      functionalized with recognition ligands, have a strong affinity toward analytes;
      therefore, they allow the enrichment of biomolecules, leading to improved
      sensitivity with minimal matrix interference in their mass spectra. SALDI-MS
      using NPs overcomes the two major problems commonly encountered in matrix
      assisted laser desorption/ionization mass spectrometry: the presence of "sweet
      spots" and the high background signals in the low-mass region. In this tutorial
      review, we discuss the roles played by the nature, size, and concentration of the
      NPs, the buffer composition, and the laser energy in determining the sensitivity
      and mass ranges for the analytes. We describe internal standard SALDI-MS methods
      that allow the concentrations of analytes to be determined with low variation
      (relative standard deviations: <10%) and we highlight how the simplicity,
      sensitivity, and reproducibility of SALDI-MS approaches using various NPs allow
      the analyses of proteins and small analytes and the imaging of cells.

PMID- 21088774
TI  - Separation and detection of rare cells in a microfluidic disk via negative
      selection.
AB  - Cyto-analysis of rare cells often requires separation and detection with each
      procedure posing substantial challenges. This paper presents a disk-based
      microfluidic platform for both procedures via an immunomagnetic negative
      selection process. The microfluidic platform's unique features include a
      multistage magnetic gradient to trap labeled cells in double trapping areas,
      drainage of fluid to substantially shorten detection time, and a bin-like regions
      to capture target cells to facilitate a seamless enumeration process. Proof-of
      concept was conducted using MCF7 as target rare cells (stained with anti
      cytokeratin-FITC antibodies) spiked into Jurkat Clone E6-1 non-target cells
      (labeled with anti-CD45-PE and anti-PE BD magnetic beads). Then, mononuclear
      cells (MNC) from healthy blood donors were mixed with MCF7s, modeling rare cells,
      and tested in the disk. Results show a non-linear magnetic coupling effect of the
      multistage magnet substantially increased the trapping efficacy over that of a
      single magnet, contributing to the depletion rate of Jurkats, which reaches
      99.96%. Detection time is extensively shortened by depletion of 95% of non-cell
      containing fluid in the collection area. The average yield of detected MCF7 cells
      is near-constant 60 +/- 10% over a wide range of rarity from 10(-3) to 10(-6) and
      this yield also holds for the MCF7/MNC complex mixture. Comparison with autoMACS
      and BD IMagnet separators revealed the average yield from the disk (60%) is
      superior to that of autoMACS (37.3%) and BD IMagnet (48.3%). The advantages of
      near-constant yield, roughly 30 min of operation, an acceptable level of cell
      loss, and potentially low cost system should aid in cyto-analysis of rare cells.

PMID- 21088775
TI  - Iron-mediated one-pot formal nitrocyclization onto unactivated alkenes.
AB  - One-pot synthesis of heterocycles having a nitromethyl group was achieved by
      sequential steps that involved chloronitration of alkenes using iron(III) nitrate
      nonahydrate followed by elimination and intramolecular Michael addition. This
      reaction provides an efficient method for the synthesis of heterocycles due to
      the simple experimental procedure and the use of inexpensive reagents of low
      toxicity.

PMID- 21088776
TI  - Extracellular biosynthesis and characterization of silver nanoparticles using
      Aspergillus flavus NJP08: a mechanism perspective.
AB  - The present study demonstrates an eco-friendly and low cost protocol for
      synthesis of silver nanoparticles using the cell-free filtrate of Aspergillus
      flavus NJP08 when supplied with aqueous silver (Ag+) ions. Identification of the
      fungal isolate was based on nuclear ribosomal DNA internal transcribed spacer
      (ITS) identities. Transmission electron microscopy (TEM) and energy dispersive
      spectroscopy (EDS) revealed the formation of spherical metallic silver
      nanoparticles. The average particle size calculated using Dynamic Light
      Scattering measurements (DLS) was found to be 17+/-5.9 nm. UV-Visible and Fourier
      transform infrared (FTIR) spectroscopy confirmed the presence of extracellular
      proteins. SDS-PAGE profiles of the extracellular proteins showed the presence of
      two intense bands of 32 and 35 kDa, responsible for the synthesis and stability
      of silver nanoparticles, respectively. A probable mechanism behind the
      biosynthesis is discussed, which leads to the possibility of using the present
      protocol in future "nano-factories".

PMID- 21088777
TI  - Hybrid foams, colloids and beyond: from design to applications.
AB  - Highly internal phase emulsion (polyHIPE) materials are promising macrocellular
      foams bearing versatile applications ranging from catalysis, optics, filtration,
      insulator and so forth. In this critical review water-in-oil HIPE, oil-in-water
      HIPE and Pickering-based HIPE are discussed. Also in each above-mentioned HIPE
      family, declination between the organic, inorganic or hybrid-organic foams
      chemical nature is proposed. The polyHIPE audience is thereby strongly
      interdisciplinary in nature crossing boundaries of physical chemistry, colloids,
      polymer science, sol-gel chemistry, hybrid materials, biology and beyond (114
      references).

PMID- 21088778
TI  - The binding of CNA35 contrast agents to collagen fibrils.
AB  - CryoTEM demonstrates that a CNA35-bearing liposomal MRI contrast agent
      selectively binds to poorly assembled collagen type I as opposed to well
      assembled collagen fibrils, whereas monomeric CNA35 binds to all forms of
      collagen. It is shown that upon conjugation to liposomes and micelles CNA35 loses
      its ability to dissociate ordered collagen fibrils and thereby to create its own
      binding sites.

PMID- 21088779
TI  - A tailor-made ligand to mimic the active site of diiron enzymes: an air-oxidized
      high-valent Fe(III) h.s.(MU-O)2Fe(IV) h.s. species.
AB  - The design and first application of a new dinucleating ligand system to mimic
      high-valent oxidation states of O(2)-dependent diiron enzymes is presented.

PMID- 21088780
TI  - Electropolymerization of intercalator-grafted conducting polymer for direct and
      amplified DNA detection.
AB  - Efficient DNA intercalators comprising naphthalene diimide grafted with
      ethylenedioxythiophene monomer were successfully designed, synthesized and
      applied to mediate/promote conducting polymer growth electrochemically on
      biosensor electrodes for direct and amplified DNA detection.

PMID- 21088781
TI  - New polymorphs of isonicotinamide and nicotinamide.
AB  - For each of the well-known co-crystal formers, isonicotinamide and nicotinamide,
      a new polymorph, obtained during attempted co-crystallisation experiments, has
      been fully characterized and its stability relationship with previously reported
      forms established.

PMID- 21088782
TI  - Conformational selection or induced fit for Brinker and DNA recognition.
AB  - Brinker is the key target protein of the Drosophila Decapentaplegic morphogen
      signalling pathway. Brinker is widely expressed and can bind with DNA. NMR
      spectra suggest that apo-Brinker is intrinsically unstructured and undergoes a
      folding transition upon DNA-binding. However, the coupled mechanism of binding
      and folding is poorly understood. Here, we performed molecular dynamics (MD)
      simulations for both bound and apo-Brinker to study the mechanism. Room
      temperature MD simulations suggest that Brinker becomes more rigid and stable
      upon DNA-binding. Kinetic analysis of high-temperature MD simulations shows that
      both bound and apo-Brinker unfold via a two-state process. The time scale of
      tertiary unfolding is significantly different between bound and apo-Brinker. The
      predicted Phi-values suggest that there are more residues with native-like
      transition state ensembles (TSEs) for bound Brinker than for apo-Brinker. The
      average RMSD differences between bound and apo-Brinker and Kolmogorov-Smirnov
      (KS) test analysis illustrate that Brinker folding upon DNA-binding might obey
      induced-fit mechanism based on MD simulations. These methods can be used for the
      research of other biomolecular folding upon ligand-binding.

PMID- 21088783
TI  - Empty level structure of boryl-substituted pentacyclic heteroaromatics.
AB  - Extended pi-conjugation in molecular systems is being extensively exploited in a
      rapidly expanding range of electronic and photonic applications. The modification
      of such extended systems through the use of heteroatoms allows their tailoring to
      specific requirements. In particular, the use of the vacant boron p(pi) orbital
      can increase the electron affinity of the extended pi system in an analogous
      fashion to the p-doping of crystalline silicon used in more classical
      microelectronic devices. Experimental data on such modifications of the empty
      level structures of boron-containing pi-electron materials leading to an increase
      in their electron affinity are not available in the literature. Using Electron
      Transmission Spectroscopy, the energies of the vertical anion formation of 5
      methyl-2-furanboronic acid pinacol ester (1) and 4-methyl-3-thiopheneboronic acid
      pinacol ester (2) are measured and compared with those of the reference
      unsubstituted heteroaromatics furan and thiophene. The results are interpreted
      with the support of density functional theory (DFT) calculations with the B3LYP
      functional. DFT calculations are also used to predict the effects of boryl
      substituents on the electronic and geometrical structures of trans and cis
      thienyl thiazole.

PMID- 21088784
TI  - Radon hydrides: structure and bonding.
AB  - Quantum chemical calculations, using gradient-correct density functional at the
      BP86 level in conjunction with TZ2P basis sets, have been carried out for the
      radon hydrides HRnY (with Y = F, Cl, Br, I, CCH, CN, and NC). The bonding in HRnY
      is studied using different bond ruptures, establishing the role of those
      stabilizing (and destabilizing) factors that prevent these species to be
      dissociated. Although all HRnY systems studied here are bound equilibrium
      structures, they are metastable species with respect to the HRnY -> Rn + HY
      decomposition channel. However, the HRnY -> H + Rn + Y reaction is endothermic.
      So, these results indicate the possibility to identify the radon hydrides in
      noble-gas matrices.

PMID- 21088785
TI  - Catalytic C-H functionalization by metalloporphyrins: recent developments and
      future directions.
AB  - Metalloporphyrins are a class of versatile catalysts with the capability to
      functionalize saturated C-H bonds via several well-defined atom/group transfer
      processes, including oxene, nitrene, and carbene C-H insertions. The
      corresponding hydroxylation, amination, and alkylation reactions provide direct
      approaches for the catalytic conversion of abundant hydrocarbons into value-added
      functional molecules through C-O, C-N, and C-C bond formations, respectively.
      This tutorial review describes metalloporphyrin-based catalytic systems for the
      functionalization of different types of sp(3) C-H bonds, both inter- and
      intramolecularly, including challenging primary C-H bonds. Additional features of
      metalloporphyrin-catalyzed C-H functionalization include unusual selectivities
      and high turnover numbers.

PMID- 21088787
TI  - The coordination chemistry of small sulfur-containing molecules: a personal
      perspective.
AB  - The sulfur oxides SO, SO2 and SO3, and thioformaldehyde H2C=S and its oxides
      H2C=SO and H2C=SO2 form stable coordination compounds with a range of transition
      metals. The complexes have a rich chemistry which differs markedly from that of
      the free ligands. Typical reactions involve electrophilic additions, nucleophilic
      additions and cycloadditions. The complexes can be used as synthons to
      incorporate these small molecules as building blocks into larger structures.

PMID- 21088786
TI  - Hydrolysis of carboxyesters promoted by vanadium(V) oxyanions.
AB  - Hydrolysis of carboxylic esters p-nitrophenyl acetate (pNPA), p-nitrophenyl
      butyrate (pNPB) and p-nitrophenyl trimethyl acetate (pNPTA) was examined in
      oxovanadate solutions by means of (1)H and (51)V NMR spectroscopy. In the
      presence of a mixture of oxovanadates, the hydrolysis of carboxyester bonds in
      pNPA proceeds under physiological conditions (37  degrees C, pD = 7.4) with a
      rate constant of k(obs) = 3.0 * 10(-5) s(-1) representing an acceleration of at
      least one order of magnitude compared to the uncatalyzed cleavage. EPR and NMR
      spectra did not show evidence for the formation of paramagnetic species,
      excluding the possibility of V(+5) reduction to V(+4), and indicating that the
      cleavage of the carboxyester bond is purely hydrolytic. The pH dependence of
      k(obs) revealed that the hydrolysis is slow in acidic media but rapidly
      accelerates in basic solutions. Comparison of the rate profile with the
      concentration profile of polyoxovanadates shows a clear overlap of the k(obs)
      profile with the concentration of monovanadate (V(1)). Kinetic experiments at 37 
      degrees C using a fixed amount of pNPA and increasing amounts of V(1) permitted
      the calculation of catalytic (k(c) = 1 x10(-4) s(-1)) and formation constant for
      the pNPA-V(1) complex (K(f) = 17.5 M(-1)). The (51)V NMR spectra of a reaction
      mixture revealed broadening and shifting of the (51)V NMR resonances of the V(1)
      and V(2) upon addition of increasing amount of pNPA, suggesting a dynamic
      exchange process between vanadates and pNPA, occurring via a rapid association
      dissociation equilibrium. The origin of the hydrolytic activity of vanadate is
      most likely a combination of its nucleophilic nature and the chelating properties
      which can lead to the stabilization of the transition state.

PMID- 21088788
TI  - Heteroleptic ruthenium complexes containing uncommon 5,5'-disubstituted-2,2'
      bipyridine chromophores for dye-sensitized solar cells.
AB  - Four new heteroleptic ruthenium sensitizers [Ru(4,4'-carboxylic acid-2,2'
      bipyridine)(L)(NCS)(2)] (L = 5,5'-bis(4-octylthiophen-2-yl)-2,2'-bipyridine (1),
      5,5'-bis(N,N-diphenyl-4-aminophenyl)-2,2'-bipyridine (2), 5,5'-bis(5-(N,N
      diphenyl-4-aminophenyl)-thiophen-2-yl)-2,2'-bipyridine (3) and 5,5'-bis(4-octyl-5
      (N,N-diphenyl-4-aminophenyl)-thiophen-2-yl)-2,2'-bipyridine (4)) were
      synthesized, characterized by physicochemical and computational methods, and
      utilized as photosensitizers in nanocrystalline dye-sensitized solar cells
      (DSSCs). The lambda(max) of the metal-to-ligand charge transfer (MLCT) absorption
      of these four ruthenium dyes (527 nm for 1, 535 nm for 2, 585 nm for 3 and 553 nm
      for 4) can be tuned by various structural modifications of the ancillary ligand
      and it was shown that increasing the conjugation length of such ligand reduces
      the energy as well as the molar absorption coefficient of the MLCT band. The
      maximum incident photon to current conversion efficiency (IPCE) of 41.4% at 550
      nm, 38.6% at 480 nm, 39.4% at 470 nm and 31.1% at 480 nm for 1-, 2-, 3- and 4
      sensitized solar cells were obtained. Respectable power conversion efficiencies
      of 3.00%, 2.51%, 2.00% and 2.03% were realized, respectively, when the
      sensitizers 1, 2, 3 and 4 were used in DSSCs under the standard air mass (AM) 1.5
      sunlight illumination (versus 5.9% for standard N719).

PMID- 21088789
TI  - A novel terpyridine/benzofurazan hybrid fluorophore: metal sensing behavior and
      application.
AB  - Terpyridine/benzofurazan conjugation results in a new hybrid fluorophore of the
      colorimetric sensing ability for Fe(2+) and fluorimetric sensing ability for XII
      group cations. The improved emission properties and cell imaging ability imply it
      is a suitable platform to construct a fluorescent sensor for metal imaging in
      biological systems.

PMID- 21088791
TI  - Construction and photophysics study of supramolecular complexes composed of three
      point binding fullerene-trispyridylporphyrin dyads and zinc porphyrin.
AB  - A series of novel supramolecular complexes composed of a three-point binding
      C(60)-trispyridylporphyrin dyad (1) or C(70)-trispyridylporphyrin dyad (2) and
      zinc tetraphenylporphyrin (ZnP) were constructed by adopting a "covalent
      coordinate" bonding approach, composed of three-point binding. The dyads and self
      assembled supramolecular triads or pentads formed by coordinating the pyridine
      groups located on the dyads to ZnP, have been characterized by means of spectral
      and electrochemical techniques. The formation constants of ZnP-1 and ZnP-2
      complexes were calculated as 1.4 * 10(4) M(-1) and 2.0 * 10(4) M(-1),
      respectively, and the Stern-Volmer quenching constants K(SV) were founded to be
      2.9 * 10(4) M(-1) and 5.5 * 10(4) M(-1), respectively, which are much higher than
      those of other supramolecular complexes such as previously reported ZnP-3 (N
      ethyl-2-(4-pyridyl)-3,4-fulleropyrrolidine). The electrochemical investigations
      of these complexes suggest weak interactions between the constituents in the
      ground state. The excited states of the complexes were further monitored by time
      resolved fluorescence measurements. The results revealed that the presence of the
      multiple binding point dyads (1 or 2) slightly accelerated the fluorescence decay
      of ZnP in o-DCB relative to that of the "single-point" bound supramolecular
      complex ZnP-3. In comparison with 1 and 2, C(70) is suggested as a better
      electron acceptor relative to C(60). DFT calculations on a model of
      supramolecular complex ZnP-1 (with one ZnP entity) were performed. The results
      revealed that the lowest unoccupied molecular orbital (LUMO) is mainly located on
      the fullerene cage, while the highest occupied molecular orbital (HOMO) is mainly
      located on the ZnP macrocycle ring, predicting the formation of radical ion pair
      ZnP(+)-H(2)P-C(60)(-) during photo-induced reaction.

PMID- 21088790
TI  - Controlled manipulation of multiple cells using catalytic microbots.
AB  - Self-propelled microjet engines (microbots) can transport multiple cells into
      specific locations in a fluid. The motion is externally controlled by a magnetic
      field which allows to selectively load, transport and deliver the cells.

PMID- 21088792
TI  - A facile route to ordered mesoporous-alumina-supported catalysts, and their
      catalytic activities for CO oxidation.
AB  - Well-dispersed noble metal nanoparticles can be synthesized, and further
      stabilized under high treatment temperature, by the confinement effect of ordered
      mesoporous alumina.

PMID- 21088793
TI  - Synthesis, carbohydrate- and DNA-binding studies of cationic 2,2':6',2''
      terpyridineplatinum(II) complexes containing N- and S-donor boronic acid ligands.
AB  - A series of platinum(II) complexes of the type [Pt(trpy)L](NO(3))(n) (L = 3- or 4
      pyridineboronic acid (3- or 4-pyB, respectively), n = 2; HL = 4
      mercaptophenylboronic acid (HmpB), n = 1; trpy = 2,2':6',2''-terpyridine) and
      [{Pt(trpy)}(2)(MU-pzB)](NO(3))(3) (HpzB = 4-pyrazoleboronic acid) were
      synthesized and fully characterized by means of multinuclear ((1)H, (13)C, (11)B,
      and (195)Pt) 1D- and 2D-NMR spectroscopy and elemental analysis. The triflate
      derivatives [Pt(trpy)(4-pyB)](OTf)(2) and [{Pt(trpy)}(2)(MU-pzB)](OTf)(3) were
      also prepared, and their molecular structures were confirmed by X-ray
      crystallography. Variable pH (1)H NMR spectroscopy showed that hydroxylation of
      the boronic acid group occurs in aqueous solution at pH > 5 and the pK(a) values
      for the complexes were determined. In buffered aqueous solution (pH 7.4), the
      complexes bind strongly to simple diols such as catechol and monosaccharides
      including D-fructose, D-ribose, D-sorbitol and D-mannitol, as determined by
      isothermal titration calorimetry (ITC). The equilibrium binding constants for
      these reactions were determined and were found to exceed those of organic boronic
      acids such as phenylboronic acid by an order of magnitude or greater, an effect
      that can be directly attributed to the cationic charge of the complexes. 2D-NMR
      methods (HSQC and HMBC) were used to elucidate the structures of the carbohydrate
      adducts [Pt(trpy)(3-pyB)].D-fructose.NO(3) and [Pt(trpy)(4-pyB)].D-fructose.NO(3)
      in aqueous solution. DNA-binding experiments with calf-thymus DNA (CT-DNA)
      indicate an avid DNA-binding interaction by the mononuclear complexes, as
      determined using thermal melting methods and ITC, but the behaviour of the
      dinuclear species [{Pt(trpy)}(2)(MU-pzB)](NO(3))(3) is complicated and could not
      be modeled adequately; higher ionic strength solutions and lower temperatures
      resulted in a similar DNA binding interaction to the mononuclear complexes. The
      presence of excess d-fructose did not significantly affect the binding of the
      platinum(II)-trpy complexes to CT-DNA.

PMID- 21088794
TI  - Hydrothermal synthesis and structure evolution of hierarchical cobalt sulfide
      nanostructures.
AB  - Hierarchical and well-defined cobalt sulfide with flower-like, cube-like, ball
      like, and surface hollowed-out nanostructures were successfully prepared by a
      facile one-pot hydrothermal synthesis approach, employing Co(NO(3))(2).6H(2)O as
      a cobalt precursor and thiourea as a sulfur source. The morphologies of these
      structures can be easily controlled by simply adjusting the molar ratio of
      reactants and solvents, reaction time, reaction temperature, and ligand types.
      Thiourea plays two important roles in the growth process of CoS nanostructures.
      First, it is decomposed to produce S(2-) for the final formation of CoS. On the
      other hand, it serves as a structure-directing agent to control the crystalline
      growth of CoS. The electrochemical capacitance performances of the CoS
      nanostructures were studied, and the flower-like CoS nanostructures show the best
      charge-discharge performance among all CoS products with the highest specific
      capacitance values of 389 F g(-1) at current density of 5 mA cm(-2), and 277 F g(
      1) at higher current density of 50 mA cm(-2).

PMID- 21088795
TI  - Multilayer perceptron neural network for flow prediction.
AB  - Artificial neural networks (ANNs) have proven to be a tool for characterizing,
      modeling and predicting many of the non-linear hydrological processes such as
      rainfall-runoff, groundwater evaluation or simulation of water quality. After
      proper training they are able to generate satisfactory predictive results for
      many of these processes. In this paper they have been used to predict 1 or 2 days
      ahead the average and maximum daily flow of a river in a small forest headwaters
      in northwestern Spain. The inputs used were the flow and climate data
      (precipitation, temperature, relative humidity, solar radiation and wind speed)
      as recorded in the basin between 2003 and 2008. Climatic data have been utilized
      in a disaggregated form by considering each one as an input variable in ANN(1),
      or in an aggregated form by its use in the calculation of evapotranspiration and
      using this as input variable in ANN(2). Both ANN(1) and ANN(2), after being
      trained with the data for the period 2003-2007, have provided a good fit between
      estimated and observed data, with R(2) values exceeding 0.95. Subsequently, its
      operation has been verified making use of the data for the year 2008. The
      correlation coefficients obtained between the data estimated by ANNs and those
      observed were in all cases superior to 0.85, confirming the capacity of ANNs as a
      model for predicting average and maximum daily flow 1 or 2 days in advance.

PMID- 21088796
TI  - In vivo sodium concentration continuously monitored with fluorescent sensors.
AB  - Sodium balance is vital to maintaining normal physiological function. Imbalances
      can occur in a variety of diseases, during certain surgical operations or during
      rigorous exercise. There is currently no method to continuously monitor sodium
      concentration in patients who may be susceptible to hyponatremia. Our approach
      was to design sodium specific fluorescent sensors capable of measuring
      physiological fluctuations in sodium concentration. The sensors are submicron
      plasticized polymer particles containing sodium recognition components that are
      coated with biocompatible poly(ethylene) glycol. Here, the sensors were brought
      up in saline and placed in the subcutaneous area of the skin of mice by simple
      injection. The fluorescence was monitored in real time using a whole animal
      imager to track changes in sodium concentrations. This technology could be used
      to monitor certain disease states or warn against dangerously low levels of
      sodium during exercise.

PMID- 21088797
TI  - Controlled mechanical fracture for fabricating microchannels with various size
      gradients.
AB  - We present a simple method to generate cracks with controllable size (depth and
      width) and space gradients using deep surface oxidation and anisotropic
      mechanical stretching. To generate a thick oxidation layer (<~7 um), a
      polydimethylsiloxane (PDMS) slab of uniform or varying thickness was exposed to
      UV/ozone for less than 30 min in the UV-C wavelength including wavelengths of 185
      and 254 nm. Subsequently, the PDMS slab was wrapped on a cylindrical support
      (radius: 11 mm) to apply a uniform bending strain (<21%), resulting in equally
      separated, anisotropic cracks over a large area. By modulating initial oxidation
      depth and applied bending stress, cracks of varying sizes and spaces were formed
      on a single PDMS slab. Furthermore, multiple, sequential cracks were generated by
      increasing the strain in a step-wise fashion and multi-directional cracks by
      applying the strain with an orientation angle. Finally, size and space-varying
      cracks were formed between two adjacent large channels in an interconnected
      format by selective masking and irreversible bonding.

PMID- 21088798
TI  - Complex coordination of multi-scale cellular responses to environmental stress.
AB  - Cells and organisms are regularly exposed to a variety of stresses, and effective
      responses are a matter of survival. The article describes a multi-scale
      experimental and dynamical modeling analysis that clearly indicates concerted
      stress control in different temporal and organizational domains, and a strong
      synergy between the dynamics of genes, proteins and metabolites. Specifically, we
      show with in vivo NMR measurements of metabolic profiles that baker's yeast
      responds to a paradigmatic stress, heat, at three organizational levels and in
      two time regimes. At the metabolic level, an almost immediate response is
      mounted. However, this response is a "quick fix" in comparison to a much more
      effective response that had been pre-organized in earlier periods of heat stress
      and is an order of magnitude stronger. Equipped with the metabolic profile data,
      our modeling efforts resulted in a crisp, quantitative separation of response
      actions at the levels of metabolic control and gene regulation. They also led to
      predictions of necessary changes in protein levels and clearly demonstrated that
      formerly observed temperature profiles of key enzyme activities are not
      sufficient to explain the accumulation of trehalose as an immediate response to
      sudden heat stress.

PMID- 21088799
TI  - Synthesis of proteins with defined posttranslational modifications using the
      genetic noncanonical amino acid incorporation approach.
AB  - Posttranslational modifications modulate the activities of most eukaryotic
      proteins and play a critical role in all aspects of cellular life. Understanding
      functional roles of these modifications requires homogeneously modified proteins
      that are usually difficult to purify from their natural sources. An emerging
      powerful tool for synthesis of proteins with defined posttranslational
      modifications is to genetically encode modified amino acids in living cells and
      incorporate them directly into proteins during the protein translation process.
      Using this approach, homogenous proteins with tyrosine sulfation, tyrosine
      phosphorylation mimics, tyrosine nitration, lysine acetylation, lysine
      methylation, and ubiquitination have been synthesized in large quantities. In
      this review, we provide a brief introduction to protein posttranslational
      modifications and the genetic noncanonical amino acid (NAA) incorporation
      technique, then discuss successful applications of the genetic NAA incorporation
      approach to produce proteins with defined modifications, and end with challenges
      and ongoing methodology developments for synthesis of proteins with other
      modifications.

PMID- 21088800
TI  - Enantiospecific synthesis of 2-[18F]fluoro-L-phenylalanine and 2-[18F]fluoro-L
      tyrosine by isotopic exchange.
AB  - 2-[(18)F]Fluoro-L-phenylalanine and 2-[(18)F]fluoro-L-tyrosine have been
      developed as promising radiopharmaceuticals for molecular imaging using positron
      emission tomography (PET). However, the lack of a convenient radiosynthetic
      pathway has limited their practical use. In this work a new three-step
      nucleophilic synthesis of these compounds starting from [(18)F]fluoride is
      described. Corresponding precursors (1a and 1b) were (18)F-fluorinated by
      isotopic exchange, followed by the removal of an activating formyl group with
      Rh(PPh(3))(3)Cl and subsequent hydrolysis of protecting groups in acidic medium.
      All reactions were carried out using both conventional and microwave heating.
      Conventional heated reactions yielded the desired products 2-[(18)F]Fphe and 2
      [(18)F]Ftyr in 43% and 49% whereas radiochemical yields of 34% and 43%,
      respectively, were obtained when they were heated by microwaves. Under optimized
      conditions the enantiomeric purity was >=94% for both radiopharmaceuticals.

PMID- 21088801
TI  - Tris(indolyl)methene molecule as an anion receptor and colorimetric chemosensor:
      tunable selectivity and sensitivity for anions.
AB  - Simple tris(indolyl)methene receptors 1-3 containing conjugated bisindole
      skeletons have been designed and synthesized. The anion binding and sensing
      properties have been studied using UV-vis spectroscopy and (1)H NMR titration
      technique. Compared with 3,3'-bis-indolyl phenylmethene (4), tris(indolyl)methene
      receptors could highly selectively detect F(-) based on two stages of proton
      transfer, along with stepwise drastic color changes. The introduction of the
      electron withdrawing or donating groups into indole unit, which tunes the
      acidities of the hydrogen bond sites, partially enhanced or inhibited the
      occurrence of the deprotonation of receptor and has a positive effect on the
      selectivity and sensitivity of such "proton-transfer" chemosensors for anions.

PMID- 21088802
TI  - Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal
      nitric oxide synthase inhibitor, in rats.
AB  - 7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and
      reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the
      present study was to determine if the anti-dyskinetic effect of 7-NI was subject
      to tolerance after repeated treatment and if this drug could interfere with the
      priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral
      depletion of dopamine in the substantia nigra compacta were treated with l-DOPA
      (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received
      ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received
      l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l
      DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an
      abnormal involuntary movement scale and a stepping test. All rats had a similar
      initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l
      DOPA and the effect was maintained during the experiment before 7-NI, median
      (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63);
      day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13),
      and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P <
      0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before
      the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5,
      NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal
      nitric oxide synthase inhibitor does not develop over a short-term period of
      repeated administration. These observations open a possible new therapeutic
      approach to motor complications of chronic l-DOPA therapy in patients with
      Parkinson's disease.

PMID- 21088803
TI  - In vitro activity of hypnophilin from Lentinus strigosus: a potential prototype
      for Chagas disease and leishmaniasis chemotherapy.
AB  - Hypnophilin and panepoxydone, terpenoids isolated from Lentinus strigosus, have
      significant inhibitory activity on Trypanosoma cruzi trypanothione reductase
      (TR). Although they have similar TR inhibitory activity at 10 MUg/mL (40.3 MUM
      and 47.6 MUM for hypnophilin and panepoxydone, respectively; ~100%), hypnophilin
      has a slightly greater inhibitory activity (~71%) on T. cruzi amastigote (AMA)
      growth in vitro as well as on in vitro phytohemagglutinin (PHA)-induced
      peripheral blood mononuclear (PBMC) proliferation (~70%) compared to panepoxydone
      (69% AMA inhibition and 91% PBMC inhibition). Hypnophilin and panepoxydone at
      1.25 MUg/mL had 67% inhibitory activity onLeishmania (Leishmania) amazonensis
      amastigote-like (AMA-like) growth in vitro. The panepoxydone activity was
      accompanied by a significant inhibitory effect on PHA-induced PBMC proliferation,
      suggesting a cytotoxic action. Moreover, incubation of human PBMC with
      panepoxydone reduced the percentage of CD16(+) and CD14(+) cells and down
      regulated CD19(+), CD4(+) and CD8(+) cells, while hypnophilin did not alter any
      of the phenotypes analyzed. These data indicate that hypnophilin may be
      considered to be a prototype for the design of drugs for the chemotherapy of
      diseases caused by Trypanosomatidae.

PMID- 21088804
TI  - Transplantation of muscle-derived stem cells plus biodegradable fibrin glue
      restores the urethral sphincter in a pudendal nerve-transected rat model.
AB  - We investigated whether fibrin glue (FG) could promote urethral sphincter
      restoration in muscle-derived stem cell (MDSC)-based injection therapies in a
      pudendal nerve-transected (PNT) rat, which was used as a stress urinary
      incontinence (SUI) model. MDSCs were purified from the gastrocnemius muscles of 4
      week-old inbred female SPF Wistar rats and labeled with green fluorescent
      protein. Animals were divided into five groups (N = 15): sham (S), PNT (D),
      PNT+FG injection (F), PNT+MDSC injection (M), and PNT+MDSC+FG injection (FM).
      Each group was subdivided into 1- and 4-week groups. One and 4 weeks after
      injection into the proximal urethra, leak point pressure (LPP) was measured to
      assess urethral resistance function. Histology and immunohistochemistry were
      performed 4 weeks after injection. LPP was increased significantly in FM and M
      animals after implantation compared to group D (P < 0.01), but was not different
      from group S. LPP was slightly higher in the FM group than in the M group but
      there was no significant difference between them at different times. Histological
      and immunohistochemical examination demonstrated increased numbers of surviving
      MDSCs (109 +/- 19 vs 82 +/- 11/hpf, P = 0.026), increased muscle/collagen ratio
      (0.40 +/- 0.02 vs 0.34 +/- 0.02, P = 0.044), as well as increased microvessel
      density (16.9 +/- 0.6 vs 14.1 +/- 0.4/hpf, P = 0.001) at the injection sites in
      FM compared to M animals. Fibrin glue may potentially improve the action of
      transplanted MDSCs to restore the histology and function of the urethral
      sphincter in a SUI rat model. Injection of MDSCs with fibrin glue may provide a
      novel cellular therapy method for SUI.

PMID- 21088805
TI  - Coronary artery calcification is associated with insulin resistance index in
      patients with type 1 diabetes.
AB  - The objective of the present study was to evaluate the risk factors associated
      with the presence of coronary artery calcification (CAC) in patients with type 1
      diabetes (T1D). A cross-sectional study was conducted on 100 consecutive T1D
      patients without coronary artery disease, with at least 5 years of diabetes and
      absence of end-stage renal disease. Mean age was 38 +/- 10 years and 57% were
      males. CAC score was measured by multidetector computed tomography (Siemens
      Sensation 64 Cardiac). The insulin resistance index was measured using the
      estimated glucose disposal rate (eGDR). The eGDR was lower among CAC-positive
      patients than among CAC-negative patients, suggesting an increased insulin
      resistance. In a logistic regression model adjusted for age (at 10-year
      intervals), eGDR, diabetic nephropathy and gender, CAC was associated with age
      [OR = 2.73 (95%CI = 1.53-4.86), P = 0.001] and with eGDR [OR = 0.08 (95%CI = 0.02
      0.21), P = 0.004]. In T1D subjects, insulin resistance is one of the most
      important risk factors for subclinical atherosclerosis.

PMID- 21088806
TI  - Impact of a 2-year intervention program on cardiometabolic profile according to
      the number of goals achieved.
AB  - We investigated the impact of lifestyle goal achievement on cardiovascular risk
      factors after a 2-year behavioral intervention program applied to 394 adults (113
      with diabetes, mean age 60.2 +/- 11.4 years, 56% women) and targeting four goals:
      >=5% weight loss; >=150 min/week physical activities; <10% saturated fat
      intake/day; >=400 g fruit and vegetable intake/day. Baseline characteristics and
      changes in variables after intervention among the four categories of number of
      goals achieved (none, 1, 2, and >=3) were compared by independent ANOVA or the
      Kruskal-Wallis test. Individuals without diabetes achieving a higher number of
      goals were more likely to be older (3 or 4 goals: 61.8 +/- 12.6 years vs none:
      53.3 +/- 10.3 years, P < 0.05) and to have a lower mean BMI (3 or 4 goals: 21.7
      +/- 2.6 kg/m2 vs none: 29.0 +/- 4.8 kg/m2, P < 0.05), diastolic blood pressure (3
      or 4 goals: 77.3 +/- 2.1 mmHg vs none: 85.4 +/- 9.6 mmHg, P < 0.05), triglyceride
      (3 or 4 goals: 116.1 +/- 95.1 mg/dL vs none: 144.8 +/- 65.5 mg/dL, P < 0.05) and
      insulin levels (3 or 4 goals: 3.6 +/- 2.4 MUU/L vs none: 5.7 +/- 4.0 MUU/L, P <
      0.05) than those achieving fewer goals. The absolute changes in cardiovascular
      risk factors tended to be more pronounced with increasing number of goals
      achieved in individuals without diabetes. The intervention had a beneficial
      impact on the cardiometabolic profile of individuals with normal or altered
      glucose metabolism. The number of goals achieved in this lifestyle intervention
      was associated with the magnitude of improvement of cardiovascular risk factors
      in individuals without diabetes. Participants with a better cardiometabolic
      profile seemed to be more likely to have a healthy lifestyle.

PMID- 21088807
TI  - Effect of hormone replacement on exercise cardiopulmonary reserve and recovery
      performance in subclinical hypothyroidism.
AB  - Subclinical hypothyroidism (SH) patients present cardiopulmonary, vascular and
      muscle dysfunction, but there is no consensus about the benefits of levothyroxine
      (L-T4) intervention on cardiopulmonary performance during exercise. The aim of
      the present study was to investigate the effects of L-T4 on cardiopulmonary
      exercise reserve and recovery in SH patients. Twenty-three SH women, 44 (40-50)
      years old, were submitted to two ergospirometry tests, with an interval of 6
      months of normalization of thyroid-stimulating hormone (TSH) levels (L-T4
      replacement group) or simple observation (TSH = 6.90 MUIU/mL; L-T4 = 1.02 ng/dL).
      Patients with TSH >10 MUIU/mL were excluded from the study to assure that they
      would receive treatment in this later stage of SH. Twenty 30- to 57-year-old
      women with no thyroid dysfunction (TSH = 1.38 MUIU/mL; L-T4 = 1.18 ng/dL) were
      also evaluated. At baseline, lower values of gas exchange ratio reserve (0.24 vs
      0.30; P < 0.05) were found for SH patients. The treated group presented greater
      variation than the untreated group for pulmonary ventilation reserve (20.45 to
      21.60 L/min; median variation = 5.2 vs 25.09 to 22.45 L/min; median variation = 
      4.75, respectively) and for gas exchange ratio reserve (0.19 to 0.27; median
      variation = 0.06 vs 0.28 to 0.18; median variation = -0.08, respectively). There
      were no relevant differences in cardiopulmonary recovery for either group at
      baseline or after follow-up. In the sample studied, L-T4 replacement improved
      exercise cardiopulmonary reserve, but no modification was found in recovery
      performance after exercise during this period of analysis.

PMID- 21088808
TI  - Spontaneous miscarriages and infant deaths among female farmers in rural South
      Africa.
AB  - OBJECTIVES: This study examined associations of demographics and occupational
      factors with spontaneous miscarriages and infant deaths among women working in
      agriculture in KwaZulu-Natal, South Africa. METHOD: This cross-sectional study in
      2006 described and compared reproductive outcomes among 911 women working in
      agriculture in two distinct areas (ie, the irrigation scheme and drylands) of the
      Makhatini Flats, KwaZulu-Natal, South Africa. Associations between demographics,
      agricultural activities, physical load, pesticide spraying and self-reported
      "spontaneous miscarriage" and "infant death" (death in the first year) were
      explored using univariate and multivariate analyses. Results Women (N=887)
      reported 4796 pregnancies, 322 spontaneous miscarriages, 137 infant deaths.
      Adjusting for age, education, and length of recall of pregnancy, spraying
      pesticides during the first three months of a pregnancy was associated with
      spontaneous miscarriage [irrigation scheme odds ratio (OR) 2.8, (95% CI) 1.1-7.2;
      drylands OR 2.5, 95% CI 1.2-5.6]. Irrigation scheme women aged >= 40 years were
      more likely to report spontaneous miscarriage (OR 3.1, 95% CI 1.2-8.2). Owning
      one's farm or working a family farm among irrigation scheme women (OR: 2.3; 95 %
      CI 1.2-4.4) and working for >= 10 years among drylands women (OR 2.1, 95 % CI 1.1
      4.3) were associated with infant death. Weeding was inversely associated with
      infant death among irrigation scheme women (OR 0.4, 95 % CI 0.2-0.7). CONCLUSION:
      This study found that women reporting spontaneous miscarriage were more likely to
      have sprayed pesticides during pregnancy, and those reporting infant death were
      more likely to have owned their farms and worked longer in agriculture.

PMID- 21088809
TI  - Hemojuvelin and hepcidin gene mutations in patients with porphyria cutanea tarda
      from Southern France.

PMID- 21088810
TI  - Central nuclear palisading in nodular basal cell carcinoma: Morphological and
      immunohisto-chemical concerns.

PMID- 21088811
TI  - Chronic renal graft rejection-associated bullous pemphigoid: A cross-reactive
      immune response?

PMID- 21088812
TI  - Anti-p155/140 antibody-positive dermatomyositis with metastasis originating from
      an unknown site.

PMID- 21088813
TI  - Tolerability and safety of biological therapies for psoriasis in daily clinical
      practice: a study of 103 Italian patients.
AB  - Studies comparing the safety and tolerability of biological therapies for
      psoriasis in the long-term and in daily clinical practice are lacking. Most
      published studies are of selected patients with short-term (3-6 months) follow
      up. We performed a retrospective cohort study of 103 patients in order to
      describe the frequency and the clinical features of adverse events, and to
      evaluate and compare the tolerability and safety of efalizumab, etanercept,
      infliximab, and adalimumab in clinical practice. A total of 136 courses of
      biological therapies were administered, with a mean duration of 16
      months/patient; 55 patients received efalizumab, 45 etanercept, 33 infliximab,
      and 3 adalimumab. Infliximab had an incidence rate ratio of suspension due to
      severe adverse events 5.9 times (95% confidence interval (95% CI) 1.9-18, p <
      0.001) higher than etanercept and 9.8 times (95% CI 3.2-30.1, p < 0.001) higher
      than efalizumab. Safety profiles for efalizumab and etanercept were more
      favourable than for infliximab. Concerning tolerability, we found that more
      patients responded to infliximab, but long-term tolerability was higher for both
      efalizumab and etanercept due to the better safety profile and a higher
      compliance to therapy.

PMID- 21088814
TI  - [Complication following embolization of a meningioma].
AB  - This report concerns a 41-year-old female patient with a huge meningioma which
      was preoperatively embolized with polyvinyl alcohol particles (PVA, 100-300 MUm)
      via the left middle meningeal artery. Dangerous vascular anastomoses were not
      previously recognized in a superselective angiography. Aphasia and hemiparesis on
      the right side occurred immediately after the embolization. A cerebral infarct
      was seen in the region of the left pericallosal artery. The patient applied to
      the fact-finding board for medical liability and a neuroradiologic opinion was
      requested. The board came to the conclusion that no incorrect medical treatment
      had been carried out.

PMID- 21088816
TI  - [Skin and pregnancy].

PMID- 21088815
TI  - [Jehova's Witnesses and severe injury with impending hemorrhaging : how complex
      is the treatment?].
AB  - Hemorrhage is frequently seen during the early phases of polytrauma management
      and intensive care treatment of the severely injured. Traumatic coagulopathy as
      well as the sometimes overlooked hyperfibrinolysis may lead to further
      complications. Therefore, transfusion of blood products and coagulation factors
      is often crucial. Jehova's Witnesses reject transfusions of blood and blood
      products due to religious convictions. In this case report a therapeutic approach
      of a multiple trauma patient suffering from traumatic brain injury, blunt chest
      trauma and liver laceration is described, who has been treated without blood
      products. As one main focus, ethical as well as legal aspects are discussed.
      Beside therapeutic concepts, such as the administration of coagulation factors,
      recombinant erythropoietin and iron, ethical and legal aspects remain part of the
      controversial discussion.

PMID- 21088817
TI  - [Allergic diseases in pregnancy. Overview of diagnosis and therapy].
AB  - Allergic diseases arising in pregnancy may pose a challenge. Skin test results
      may be influenced by hormonal factors and fetal risk due to the skin testing
      procedure cannot be excluded. Also, several anti-allergic drugs are not licensed
      or are even contraindicated in pregnancy. This paper reviews diagnostic and
      therapeutic procedures in pregnant women.

PMID- 21088818
TI  - Innocent until proven guilty? Stable coexistence of alien rainbow trout and
      native marble trout in a Slovenian stream.
AB  - To understand the consequences of the invasion of the nonnative rainbow trout
      Oncorhynchus mykiss on the native marble trout Salmo marmoratus, we compared two
      distinct headwater sectors where marble trout occur in allopatry (MTa) or
      sympatry (MTs) with rainbow trout (RTs) in the Idrijca River (Slovenia). Using
      data from field surveys from 2002 to 2009, with biannual (June and September)
      sampling and tagging from June 2004 onwards, we analyzed body growth and survival
      probabilities of marble trout in each stream sector. Density of age-0 in
      September over the study period was greater for MTs than MTa and very similar
      between MTs and RTs, while density of trout >=age-1 was similar for MTa and MTs
      and greater than density of RTs. Monthly apparent survival probabilities were
      slightly higher in MTa than in MTs, while RTs showed a lower survival than MTs.
      Mean weight of marble and rainbow trout aged 0+ in September was negatively
      related to cohort density for both marble and rainbow trout, but the relationship
      was not significantly different between MTs and MTa. No clear depression of body
      growth of sympatric marble trout between sampling intervals was observed. Despite
      a later emergence, mean weight of RTs cohorts at age 0+ in September was
      significantly higher than weight of both MTs and MTa. The establishment of a self
      sustaining population of rainbow trout does not have a significant impact on body
      growth and survival probabilities of sympatric marble trout. The numerical
      dominance of rainbow trout in streams at lower altitudes seem to suggest that
      while the low summer flow pattern of Slovenian streams is favorable for rainbow
      trout invasion, the adaptation of marble trout to headwater environments may
      limit the invasion success of rainbow trout in headwaters.

PMID- 21088819
TI  - [Positions for medical doctors in German hospitals for psychiatry and
      psychotherapy].
AB  - As in other medical specialties, there is currently an imbalance between the
      number of open positions and the number of applicants in the field of psychiatry
      and psychotherapy, despite an overall growing number of physicians. To assess the
      magnitude of this deficit, the German Association for Psychiatry and
      Psychotherapy (DGPPN) conducted a survey among heads of clinics for psychiatry
      and psychotherapy in Germany. There were several characteristic trends: there is
      high variability in the lack of applicants depending on the contextual conditions
      of the specific clinic. It increased significantly from 2008 to 2009, is more
      pronounced in the east rather than in the west, in smaller rather than in larger
      clinics, and for assistant doctors rather than for specialists. The lack of
      applicants is most likely also masked by compensatory measures such as the hiring
      of psychologists for the position of a physician. It is assumed that in addition
      to the general lack of physicians there is a specialty-specific component that
      plays a role: the disproportionate increase in the demand for psychiatric
      psychotherapeutic services.

PMID- 21088820
TI  - [Patient in a posthypoxic vegetative state. Favorable outcome despite unfavorable
      prognostic parameters].

PMID- 21088821
TI  - [Structural and functional neuroimaging of the pathophysiology of apraxia].
AB  - A better understanding of the neural bases of apraxia is an important
      prerequisite to develop new therapeutic strategies for the disabling apraxic
      deficits after left-hemisphere stroke, like disturbed imitation of gestures,
      deficient pantomime, and object use deficits. Recently, functional and structural
      imaging methods allowed deeper insights into the pathophysiology of apraxia:
      While apraxic object use deficits result from the dysfunction of an extended
      fronto-parietal network within the left hemisphere, pantomime deficits are caused
      by impaired functioning of the left inferior frontal cortex. Further apraxia
      related, motor cognitive processes (i.e., gesture imitation, integration of
      temporal and spatial movement information, and intentional movement planning)
      depend on the integrity of the left parietal cortex. Newly developed functional
      and structural imaging methods, like dynamic causal modelling (DCM) and diffusion
      tensor imaging (DTI), promise to further elucidate the pathophysiology of apraxia
      at the network level.

PMID- 21088822
TI  - [Functional imaging of locomotion and navigation. Physiology and
      neurodegeneration].
AB  - In humans, central control of gait and spatial orientation can be visualized by
      functional neuroimaging techniques. However, in many cases data acquisition has
      to be uncoupled from the actual movement in space. Optic and PET methods allow
      the measurement of brain activity during real overground walking. Virtual
      reality, mental imagination, and the reduction to basic movement components (foot
      movement) are used in functional MRI to image different aspects of the locomotor
      network. Results show that - in humans as in cats - the locomotor signal is
      transmitted from the frontal cortex via basal ganglia and locomotor regions in
      the brain stem and cerebellum to the spinal pattern generators. The hippocampal
      formation (on the right side) and its interaction with frontal and parietal
      cortex are essential for spatial navigation. Functional imaging of gait in
      patients is still in its infancy, but already broadens the knowledge on the
      pathophysiology of gait disturbances in degenerative brain disease.

PMID- 21088823
TI  - Acute toxicity of the dissociating veterinary antibiotics trimethoprim to Willow
      trees at varying pH.
AB  - The willow tree acute toxicity test was applied to determine the acute toxicity
      of the neutral and the ionic form of the antibiotic trimethoprim (TMP) to trees.
      The pKa of the weak base TMP is at 7.2, and the toxicity testing was done at low
      (pH 4.3), medium (pH 6.4) and high pH (pH 8.15). The test gave toxic effects,
      i.e. reduced transpiration at an external concentration of 100 mg/L TMP at medium
      and high pH, where the neutral form of TMP dominates. At an external
      concentration of 1,000 mg/L, also at low pH an effect occurred, but it was less
      pronounced than at medium pH.

PMID- 21088824
TI  - Impact of fertilizers on heavy metal loads in surface soils in Nzoia nucleus
      Estate Sugarcane Farms in Western Kenya.
AB  - Analysis of heavy metals in top soil samples from Nzoia sugarcane farms in
      Western Kenya found elevated levels of heavy metals in the soils with mean
      concentrations (mg kg-1 dry weight) of 142.38, 59.12, 73.35, 116.27, 409.84 (dry
      season) and 144.22, 50.29, 72.14, 158.81, 368.83 (wet season) for Cr, Pb, Cu, Zn
      and Fe, respectively, compared with a control soil sample from an adjacent field
      where fertilizers are not applied having mean concentrations of 117.27, 61.87,
      63.68, 123.49, 282.93 (dry season) 108.00, 50.68, 66.10, 114.23, 167.01 (wet
      season), respectively. The heavy metal loads in the sugarcane farms were above
      international standards. The levels of the same metals in the fertilizers used in
      the sugarcane farms were within acceptable international standards. A risk
      assessment of the continued use of phosphate fertilizer (DAP) in the farms based
      on a 50-year period, did not exceed international threshold. The soil pH values
      (6.18 dry season and 5.66 wet season) were low compared to the control (7.46 dry
      season and 7.10 wet season) a situation that could accelerate heavy metal
      solubility and mobility in the farm soil. Lowering of soil pH was attributed
      mainly to fertilizer application and partly to increased organic matter content
      as shown by the high mean total organic carbon content values of 8.63% (dry
      season) and 8.43 (wet season) in comparison with a control soil meant total
      organic carbon content value of 4.76% (dry season) and 5.02 (wet season).

PMID- 21088825
TI  - Desiccation tolerance in Staphylococcus aureus.
AB  - Staphylococcus aureus is a multidrug-resistant pathogen that not only causes a
      diverse array of human diseases, but also is able to survive in potentially dry
      and stressful environments, such as the human nose, on skin and on inanimate
      surfaces such as clothing and surfaces. This study investigated parameters
      governing desiccation tolerance of S. aureus and identified several components
      involved in the process. Initially, the role of environmental parameters such as
      temperature, growth phase, cell density, desiccation time and protectants in
      desiccation tolerance were determined. This established a robust model of
      desiccation tolerance in which S. aureus has the ability to survive on dry
      plastic surfaces for more than 1,097 days. Using a combination of a random screen
      and defined mutants, clpX, sigB and yjbH were identified as being required for
      desiccation tolerance. ClpX is a part of the ATP-dependent ClpXP protease,
      important for protein turnover, and YjbH has a proposed linked function. SigB is
      an accessory sigma factor with a role in generalized stress resistance.
      Understanding the molecular mechanisms that govern desiccation tolerance may
      determine the break points to be exploited to prevent the spread of this
      dangerous pathogen in hospitals and communities.

PMID- 21088826
TI  - Delta2,3-ivermectin ethyl secoester, a conjugated ivermectin derivative with
      leishmanicidal activity but without inhibitory effect on mammalian P-type
      ATPases.
AB  - Looking at a new putative target for the large spectrum antiparasitic drug
      ivermectin, we recently showed that avermectin-derived drugs are active against
      promastigote and amastigote forms of Leishmania amazonensis at low micromolar
      concentrations. However, we then reported that at this concentration range
      ivermectin is also able to inhibit three important mammalian P-type ATPases so
      that unacceptable adverse effects could occur if this drug were used at such high
      doses therapeutically. The present work aimed to test the activity of ten
      ivermectin analogs on these rat ATPases in search of a compound with similar
      leishmanicidal activity but with no effect on the mammalian (host) ATPases at
      effective concentrations. We synthesized three new ivermectin analogs for testing
      on rat SERCA (1a and 1b), Na+, K+-ATPase (alpha1 and alpha2/alpha3 isoforms) and
      H+/K+-ATPase activity, along with seven analogs already characterized for their
      leishmanicidal activity. Our main finding is that one of the prepared
      derivatives, Delta2,3-ivermectin ethyl secoester 8, is equipotent to ivermectin 1
      for the in vitro leishmanicidal effects but is nearly without effect on the rat
      ATPases, indicating that it could have a better therapeutic index in vivo and
      could serve as a candidate for hit-to-lead progression. This conclusion is
      further supported by the fact that compound 8 produced only 6% (vs 77% for
      ivermectin) inhibition of the human kidney enzyme at 5 MUM, a concentration
      corresponding to the IC50 for the activity against L. amazonensis amastigotes.

PMID- 21088827
TI  - Ligand fishing with functionalized magnetic nanoparticles coupled with mass
      spectrometry for herbal medicine analysis: ligand fishing for herbal medicine
      analysis.
AB  - The chemical composition of herbal medicines is very complex, and their
      therapeutic effects are determined by multi-components with sophisticated
      synergistic and/or suppressive actions. Therefore, quality control of herbal
      medicines has been a formidable challenge. In this work, we describe a fast
      analytical method that can be used for quality assessment of herbal medicines.
      The method is based on ligand fishing using human-serum-albumin-functionalized
      magnetic nanoparticles (HSA-MNPs) and mass spectrometry. To demonstrate the
      applicability of the proposed method, eight samples of Dioscorea panthaica were
      analyzed. The sampled plants were of both wild and cultivated origins. They grew
      at different geographical locations and were harvested at different times. The
      ligands bound to HSA-MNPs were isolated from the plant extracts and detected by
      using direct infusion electrospray ionization mass spectrometry (DI-ESI-MS).
      Chemical identity has been confirmed for five of the ligands isolated. From more
      than 15 peaks in the ESI-MS spectrum, 11 common peaks were selected for
      calculating the correlation coefficient and cosine ratio. The values of
      correlation coefficient and cosine ratio were >0.9824 and >0.9988, respectively,
      for all the samples tested. The results indicated a high level of similarity
      among the eight D. panthaica samples. Compared with chromatographic fingerprint
      analysis, the proposed HSA-MNP-based DI-ESI-MS/MS approach was not only fast and
      easy to carry out but also biological-activity-oriented, promising a more
      effective data interpretation and thus reliable assessment conclusions.

PMID- 21088828
TI  - Production and analytical characterization of neopterin immunoreagents for
      biosensor developments.
AB  - Neopterin is a valuable biomarker of cellular immunity associated with various
      pathological situations such as viral and bacterial infections, autoimmune,
      cardiovascular, neurodegenerative and malignant disorders. To produce specific
      antibodies against neopterin for a rapid multi-biomarker-based diagnosis, a novel
      hapten derivative was synthesized and attached to carrier proteins. The
      thoroughly characterized conjugates were used for immunization of BALB/c mice and
      rabbits. The produced monoclonal antibody reached in both direct and indirect
      enzyme-linked immunosorbent assay (ELISA) format LoD of 0.18 and 0.45 MUg L(-1),
      respectively, and was a superior immunoreagent for further biosensor developments
      with regard to assay sensitivity and material availability. The best polyclonal
      antibody was somewhat more sensitive in direct ELISA with LoD of 0.05 MUg L(-1).
      The optimized ELISA method was evaluated with blood samples collected from
      patients with renal insufficiency, patients with sepsis, patients without
      confirmed clinical diagnosis, and healthy volunteers. In plasma samples,
      neopterin concentrations ranging from 3.2 to 103 MUg L(-1) could be determined
      with the monoclonal ELISA whereas twofold lower results were obtained with the
      polyclonal ELISA. A satisfactory correlation of results was found between the
      polyclonal ELISA and IBL Neopterin ELISA kit within the concentration range 0.5
      16 MUg L(-1) (R = 0.874; n = 40), and slightly lower correlation was found for
      monoclonal-based ELISA (R = 0.819; n = 40). These data show that the generated
      antibodies may be used as functional analytical reagents for the integration into
      multianalyte biochip detection systems.

PMID- 21088829
TI  - Multiple outcomes associated with the use of metformin and sulphonylureas in type
      2 diabetes: a population-based cohort study in Italy.
AB  - OBJECTIVE: To compare the effect of metformin and sulphonylureas on the risks of
      switching to insulin therapy, hospitalisation for macrovascular disease and all
      cause mortality. METHODS: The 70,437 residents of the Italian Region of Lombardy
      aged 40 to 90 years who started diabetes treatment with metformin or
      sulphonylureas during 2001-2003 entered the study and were followed until July
      2007. We estimated the effects of the first-line agent, early compliance, and
      persistence with first-line therapy on the risks of switching to insulin,
      hospitalisation for macrovascular disease and all-cause mortality, by fitting a
      multistate model and adjusting for age, gender and selected clinical factors.
      RESULTS: Compared with patients who started on metformin, those who started on
      sulphonylureas were at a higher risk of switching to insulin (adjusted hazard
      ratio and 95% CI, 1.55; 1.43, 1.68), hospitalisation (1.15; 1.08, 1.21), and
      death (1.37; 1.26, 1.49). Compared with patients who stayed on sulphonylureas for
      3 months or less, those on sulphonylureas for more than 9 months had an adjusted
      hazard ratio of 1.24 (1.13, 1.35) for switching to insulin and 1.14 (1.05, 1.23)
      for hospitalisation. The risks of switching to insulin and hospitalisation were
      both increased among patients who switched from metformin to another oral
      hypoglycaemic agent or combined initial monotherapy with another agent.
      CONCLUSIONS: Our study provides evidence that the risks of switching to insulin,
      hospitalisation because of macrovascular events and death changes according to
      the first prescribed oral hypoglycaemic agent, as well as to the early compliance
      and persistence with such agent.

PMID- 21088830
TI  - Ca2+-induced effect on mechanical properties of sulfatide-incorporated vesicles.
AB  - The Ca(2+)-induced effect on the nanomechanical properties of vesicles prepared
      at a different ratio of dipalmitoylphosphatidylcholine (DPPC)/sulfatide was
      studied using atomic force microscope (AFM) on a mica surface. Vesicles were
      prepared by extrusion and adsorbed on the mica surface. The forces, measured
      between an AFM tip and the vesicle, showed that the breakthrough of the tip into
      the vesicles occurred two times. Force data prior to the first breakthrough were
      fitted well with the Hertzian model to estimate Young's modulus and bending
      modulus of the vesicles. Sulfatide incorporation led to a decrease of around 90%
      in Young's modulus and bending modulus of the vesicles due to the hydration of
      the headgroups, while the addition of Ca(2+) induced dehydration to recover the
      properties. The change of the physical properties seems to be attributed to the
      headgroup packing order of the vesicles, which is determined by the interference
      with the hydration shell.

PMID- 21088832
TI  - Bacterial degradation of bile salts.
AB  - Bile salts are surface-active steroid compounds. Their main physiological
      function is aiding the digestion of lipophilic nutrients in intestinal tracts of
      vertebrates. Many bacteria are capable of transforming and degrading bile salts
      in the digestive tract and in the environment. Bacterial bile salt transformation
      and degradation is of high ecological relevance and also essential for the
      biotechnological production of steroid drugs. While biotechnological aspects have
      been reviewed many times, the physiological, biochemical and genetic aspects of
      bacterial bile salt transformation have been neglected. This review provides an
      overview of the reaction sequence of bile salt degradation and on the respective
      enzymes and genes exemplified with the degradation pathway of the bile salt
      cholate. The physiological adaptations for coping with the toxic effects of bile
      salts, recent biotechnological applications and ecological aspects of bacterial
      bile salt metabolism are also addressed. As the pathway for bile salt degradation
      merges with metabolic pathways for bacterial transformation of other steroids,
      such as testosterone and cholesterol, this review provides helpful background
      information for metabolic engineering of steroid-transforming bacteria in
      general.

PMID- 21088831
TI  - Abdominal imaging in child abuse.
AB  - INTRODUCTION: Abdominal injuries in abused children are less common than
      musculoskeletal and craniocerebral injuries; however they carry high mortality
      and morbidity rates. In every case of trauma, regardless of aetiology,
      radiologists are responsible for the documentation and evaluation of injuries.
      INJURIES: Any abdominal injury pattern maybe observed following physical abuse
      and none is specific for abuse. However, a high index of suspicion should be
      maintained for every case of pancreatic, hollow viscous and other solid organ
      injuries, especially when there is delay in seeking help, a history of trauma to
      the child or siblings, young age, undernourishment, ecchymosis in non-ambulatory
      children or a non-plausible explanation for the injuries based on the provided
      history and the psychomotor condition of the child. IMAGING MODALITIES: CT with
      intravenous contrast material is the imaging modality of choice in every
      suspected inflicted abdominal injury. US could be the first imaging test for
      abused children with a low probability of abdominal injury and for follow-up.
      Upper gastrointestinal series could reveal acute or resolving mural haematomas in
      children with equivocal CT or US findings. CONCLUSION: Child abuse should be
      considered in the differential diagnosis of acute abdominal symptoms in young
      children.

PMID- 21088833
TI  - Strategies for head and inlay exchange in revision hip arthroplasty.
AB  - Due to the increasing number of total hip arthroplasties performed during the
      last three decades and the limited long-term survival, mainly because of wear,
      the number of revisions has increased during the last two years. If the implant
      itself is still considered to be stable, only head and inlay exchange is
      necessary. This requires comprehensive knowledge of the characteristics of the
      articulating materials by the surgeon as the wrong choice of wear couple can lead
      to early failure for a second time. The aim of this paper is to present
      considerations and strategies for head and inlay exchange in case of failure,
      either due to wear of the articulation material or of other indications for
      revision hip arthroplasty.

PMID- 21088834
TI  - Clavicle fractures: a comparison of five classification systems and their
      relationship to treatment outcomes.
AB  - We compared five classification systems for clavicle fractures. The aim of this
      study was to evaluate the prognostic value of each system. Over a two-year period
      we reviewed all new radiographs of the shoulder region and identified 487
      clavicle fractures. Each radiograph was classified using five classification
      systems. We reviewed all subsequent X-rays and clinical records until the patient
      was discharged. We assessed each classification system's prognostic value in
      predicting delayed/non-union. Our data show that 79.3% of clavicle fractures
      occur in the middle third, 19.3% in the lateral third and 1.4% in the medial
      third. The overall prevalence of delayed/non-union was 7.3%, with 3.2% requiring
      operative management and 4.1% developing asymptomatic non-union. The incidence of
      non-union in the lateral third was 9.6%, but only 0.4% required operative
      management. Craig's classification had the greatest prognostic value for lateral
      third fractures, and Robinson's classification had the greatest prognostic value
      for middle third fractures. Fractures of the clavicle are common injuries but non
      union is an uncommon occurrence. Non-union is more common in the lateral third,
      but we found these to be mostly asymptomatic. Middle third fractures are more
      likely to require operative fixation. Middle third fractures should be classified
      according to Robinson's classification system and lateral third fractures
      according to Craig's classification. We did not assess sufficient medial third
      fractures for the data to be significant.

PMID- 21088835
TI  - Clinicopathologic characteristics of colorectal cancer patients with synchronous
      and metachronous gastric cancer.

PMID- 21088836
TI  - Possible role of F18-FDG-PET/CT in differentiating benign lesions versus
      malignant after indeterminate fine-needle aspiration cytology. a wider and still
      controversial issue: exclusion of malignancy in thyroid nodules with
      indeterminate fine-needle aspiration cytology after negative 18F
      fluorodeoxyglucose positron emission tomography: interim analysis.

PMID- 21088837
TI  - Simplified alternative to the TRISS method for resource-constrained settings.
AB  - BACKGROUND: We developed simple methods of risk adjustment for evaluating the
      quality of injury care (predicting survival probabilities of the injured) by
      fully utilizing routinely collected data in injury surveillance and clinical
      practices. Widely used methods of risk adjustment require additional data that
      are difficult to collect in resource-constrained settings. METHODS: We developed
      logistic regression models that predict survival using data obtained from 9,840
      victims aged 15 years or older with blunt traumatic injuries who were registered
      in the Japan Trauma Data Bank, Japan's national trauma registry, between January
      2004 and December 2007. The models included three predictors: age, an anatomical
      injury severity parameter such as a simplified severity categorization (minor,
      moderate, and severe) described in the Injury Surveillance Guidelines, and a
      physiological status parameter. The models' abilities to predict survival
      probabilities were evaluated using the area under the receiver-operating
      characteristic curve (AUROCC). RESULTS: The simplified three-predictor models
      showed good performance with the AUROCC ranging from 0.86 to 0.94. In particular,
      the models with a consciousness level indicator as a physiological parameter
      showed a high AUROCC, ranging from 0.93 to 0.94, which was not much different
      from the performance of the widely used method that shows an AUROCC of 0.96.
      CONCLUSIONS: Simplified methods of risk adjustment that require only routinely
      collected data will facilitate evaluation and improvement in the quality of
      injury care in resource-constrained low- and middle-income countries, where
      injuries are a growing public health concern.

PMID- 21088838
TI  - Measures to prevent surgical site infections: what surgeons (should) do.
AB  - BACKGROUND: The present study was designed to evaluate surgeons' strategies and
      adherence to preventive measures against surgical site infections (SSIs).
      MATERIALS AND METHODS: All surgeons participating in a prospective Swiss
      multicentric surveillance program for SSIs received a questionnaire developed
      from the 2008 National (United Kingdom) Institute for Health and Clinical
      Excellence (NICE) clinical guidelines on prevention and treatment of SSIs. We
      focused on perioperative management and surgical technique in hernia surgery,
      cholecystectomy, appendectomy, and colon surgery (COL). RESULTS: Forty-five of 50
      surgeons contacted (90%) responded. Smoking cessation and nutritional screening
      are regularly propagated by 1/3 and 1/2 of surgeons, respectively. Thirty-eight
      percent practice bowel preparation before COL. Preoperative hair removal is
      routinely (90%) performed in the operating room with electric clippers. About 50%
      administer antibiotic prophylaxis within 30 min before incision. Intra-abdominal
      drains are common after COL (43%). Two thirds of respondents apply nonocclusive
      wound dressings that are manipulated after hand disinfection (87%). Dressings are
      usually changed on postoperative day (POD) 2 (75%), and wounds remain undressed
      on POD 2-3 or 4-5 (36% each). CONCLUSIONS: Surgeons' strategies to prevent SSIs
      still differ widely. The adherence to the current NICE guidelines is low for many
      procedures regardless of the available level of evidence. Further research should
      provide convincing data in order to justify standardization of perioperative
      management.

PMID- 21088839
TI  - Endoscopic minimally invasive thyroidectomy (eMIT): a prospective proof-of
      concept study in humans.
AB  - BACKGROUND: We have developed a new approach for endoscopic minimally invasive
      thyroidectomy (eMIT) in anatomical studies. Safety and feasibility were
      demonstrated in an animal study and then the eMIT technique was applied for the
      first time successfully in humans on the 18 March 2009. METHODS: In a prospective
      study, we performed this eMIT technique on eight patients suffering from nodular
      change of the thyroid gland. All patients were evaluated regarding recurrent
      laryngeal nerve function, intra- and postoperative complications, and
      postoperative outcome, particularly with respect to swallowing disorders.
      RESULTS: A total thyroidectomy and a partial resection were performed in four
      cases each. In three cases, a conversion to open surgery was necessary due to
      specimen size. No local infection at the incision site or within the cervical
      spaces occurred within the direct postoperative course. No intraoperative
      bleeding necessitating conversion to open surgery was observed. In one case, a
      permanent palsy of the right recurrent laryngeal nerve was noted. Voice function
      and breathing were not affected. Paresthesia of the mental nerve did not occur in
      all patients and in those in which it did occur, it resolved within 3 weeks. Mean
      follow-up time was 10.9 months. CONCLUSIONS: The experimental development of the
      eMIT technique has led to its first clinical application in humans. In this
      prospective proof-of-concept study in humans, the thyroid gland was reached via
      the transoral endoscopic approach in an anatomically defined layer without any
      relevant damage to vessels. Limitations to this technique are determined by
      specimen volume (up to 30 ml) and nodule size (up to 20 mm).

PMID- 21088840
TI  - Clipless cholecystectomy: which sealer should be used?
AB  - BACKGROUND: The use of the Harmonic Scalpel (HS) for cystic duct ligation began
      with little data about its efficacy or safety. On the other hand, there is not
      any literature available about the use of PlasmaKinetic Sealer (PK) for closing
      the cystic duct in laparoscopic cholecystectomy (LC). Therefore, this study was
      designed to compare the efficacy and safety of HS and PK for achieving safe
      closure of the cystic ducts after LC. METHODS: Ninety patients with symptomatic
      gallstone disease were enrolled in this prospective case control study. The
      patients were operated with laparoscopic technic and divided into three groups (n
      = 30) randomly. After the dissection of Calot's triangle, proximal cystic ducts
      on common bile ducts were sealed with single surgical clips (SC) in all groups,
      and in the first group, distal of the cystic ducts also was sealed with single SC
      and the gallbladders were removed with SC. In the second and third groups, distal
      of the cystic ducts were sealed with HS and PK, respectively. The gallbladders
      were removed as sealed cystic ducts with HS and PK. Then, gallbladders were
      connected to a transducer set and increasing pressure with saline was applied.
      The bursting pressures of gallbladders were measured and differences between the
      groups were calculated by using Student's t test. The value of P < 0.05 was
      accepted as significant. RESULTS: In this study, the mean cystic duct bursting
      pressures were 332.46 +/- 4.62 mmHg with SC, 326.56 +/- 4.53 mmHg with PK, and
      343.06 +/- 4.28 mmHg with HS. Differences of the mean cystic duct bursting
      pressures between the groups were indicated the superior results of HS.
      CONCLUSIONS: The results of this study indicated that HS is more effective than
      PK and as safe and effective as SC for cystic duct closure.

PMID- 21088841
TI  - Successful antibiotic treatment of severe staphylococcal infection of a long
      stent graft in the superficial femoral artery with graft preservation in the long
      term.
AB  - INTRODUCTION: Bacterial infection of endovascular stent grafts is a serious
      condition, regularly leading to graft replacement by open bypass surgery. CASE
      REPORT: We describe the case of a staphylococcal infection of a 150-mm covered
      stent graft (Gore Viabahn), placed in the superficial femoral artery. Stent graft
      infection was successfully treated by oral administration of penicillinase
      resistant flucloxacillin and the lipopeptide daptomycin with complete graft
      preservation, not requiring surgical treatment. During 1-year follow-up, the
      graft infection did not reappear. However, the patient developed restenosis at
      the proximal margin of the stent with recurrence of mild claudication, so far
      treated conservatively. CONCLUSION: With the increased use of covered stent
      grafts in the peripheral vasculature, the frequency of graft infection will
      increase. We demonstrate that with newly developed antibiotics, it is possible to
      treat this severe complication conservatively, with complete graft preservation
      and without the need for bypass surgery in selected cases.

PMID- 21088842
TI  - Hypercarnivory and the brain: protein requirements of cats reconsidered.
AB  - The domestic hypercarnivores cat and mink have a higher protein requirement than
      other domestic mammals. This has been attributed to adaptation to a
      hypercarnivorous diet and subsequent loss of the ability to downregulate amino
      acid catabolism. A quantitative analysis of brain glucose requirements reveals
      that in cats on their natural diet, a significant proportion of protein must be
      diverted into gluconeogenesis to supply the brain. According to the model
      presented here, the high protein requirement of the domestic cat is the result of
      routing of amino acids into gluconeogenesis to supply the needs of the brain and
      other glucose-requiring tissues, resulting in oxidation of amino acid in excess
      of the rate predicted for a non-hypercarnivorous mammal of the same size. Thus,
      cats and other small hypercarnivores do not have a high protein requirement per
      se, but a high endogenous glucose demand that is met by obligatory amino acid
      based gluconeogenesis. It is predicted that for hypercarnivorous mammals with the
      same degree of encephalisation, endogenous nitrogen losses increase with
      decreasing metabolic mass as a result of the allometric relationships of brain
      mass and brain metabolic rate with body mass, possibly imposing a lower limit for
      body mass in hypercarnivorous mammals.

PMID- 21088843
TI  - Time course of right ventricular functional parameters after surgical correction
      of tetralogy of Fallot determined by cardiac magnetic resonance.
AB  - AIM: To evaluate changes of right ventricular (RV) parameters in follow-up
      examinations after corrected tetralogy of Fallot (TOF) by cardiac magnetic
      resonance (CMR). METHODS: CMR was performed twice within 4 years in 45 patients
      using a 1.5 T scanner. RV-volumes and pulmonary-regurgitant-fractions (PRF) were
      calculated from standard cine-sequences and flow-sensitive gradient-echo images,
      respectively. Patients were divided into two groups depending on the post
      operative (po) interval (group 1 <=5 years po; group 2 >5 years po) and subgroups
      depending on type of surgery (transannular vs. non-transannular). Patient groups
      were compared among each other and differences between 1st and 2nd CMR were
      assessed. Furthermore, patients were compared with 25 healthy volunteers.
      RESULTS: Compared with controls RV-size was increased (group 1: p = 0.007; group
      2: p < 0.001) and RV function decreased (group 1: p = 0.02; group 2: p < 0.001)
      in po TOF-patients. PRF was higher in group 2 compared with group 1 (p = 0.04)
      and significant changes of PRF between 1st and 2nd CMR were found in group 2 (p <
      0.01), but not in group 1 (p = 0.29). Compared with the non-transannular
      subgroup, PRF (p < 0.001) and RV end-diastolic-volume index (RV-EDVI) (p = 0.03)
      were significantly higher in patients with a transannular patch, EDVI increased
      between 1st and 2nd CMR. After correction, no significant changes of RV
      myocardial mass index (RV-MMI) were found. CONCLUSION: After correction of TOF,
      RV-size, RV-muscle mass (RV-MM) was increased and ejection fraction decreased in
      "early" follow-up already. Whereas these parameters can remain stable over a long
      time period, the PRF significantly increased in "late" follow-up dependent on the
      po interval. Overall, transannular patching went along with higher PRF and bigger
      RV-size as well as a greater dynamic of these parameters in the time course,
      which makes this subgroup highly in need of regular follow-up examinations for
      the optimal timing of re-interventions. In contrast, the increased RV-MM
      demonstrated no regression po.

PMID- 21088844
TI  - Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than
      IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable
      prognostic effect of higher age: implications for classification of gliomas.
AB  - WHO grading of human brain tumors extends beyond a strictly histological grading
      system by providing a basis predictive for the clinical behavior of the
      respective neoplasm. For example, patients with glioblastoma WHO grade IV usually
      show a less favorable clinical course and receive more aggressive first-line
      treatment than patients with anaplastic astrocytoma WHO grade III. Here we
      provide evidence that the IDH1 status is more prognostic for overall survival
      than standard histological criteria that differentiate high-grade astrocytomas.
      We sequenced the isocitrate dehydrogenase 1 gene (IDH1) at codon 132 in 382
      patients with anaplastic astrocytoma and glioblastoma from the NOA-04 trial and
      from a prospective translational cohort study of the German Glioma Network.
      Patients with anaplastic astrocytomas carried IDH1 mutations in 60%, and patients
      with glioblastomas in 7.2%. IDH1 was the most prominent single prognostic factor
      (RR 2.7; 95% CI 1.6-4.5) followed by age, diagnosis and MGMT. The sequence from
      more favorable to poorer outcome was (1) anaplastic astrocytoma with IDH1
      mutation, (2) glioblastoma with IDH1 mutation, (3) anaplastic astrocytoma without
      IDH1 mutation and (4) glioblastoma without IDH1 mutation (p < 0.0001). In this
      combined set of anaplastic astrocytomas and glioblastomas both, IDH1 mutation and
      IDH1 expression status were of greater prognostic relevance than histological
      diagnosis according to the current WHO classification system. Our data indicate
      that much of the prognostic significance of patient age is due to the predominant
      occurrence of IDH1 mutations in younger patients. Immunohistochemistry using a
      mutation-specific antibody recognizing the R132H mutation yielded similar
      results. We propose to complement the current WHO classification and grading of
      high-grade astrocytic gliomas by the IDH1 mutation status and to use this
      combined histological and molecular classification in future clinical trials.

PMID- 21088845
TI  - Proteome analyses of cultured astrocytes treated with MK-801 and clozapine:
      similarities with schizophrenia.
AB  - On the basis of impaired glutamatergic transmission and the potential role of
      astrocytes in schizophrenia, we treated cultured astrocytes with MK-801, an NMDA
      receptor antagonist, to investigate whether the resulting proteome changes are
      similar to those we found in our earlier proteome analysis of schizophrenia human
      brain tissue as well as to better comprehend the role of astrocytes in the
      disorder. Indeed, there are similarities. Furthermore, to verify the efficacy of
      clozapine and its effect over the proteome, we treated MK-801-treated astrocytes
      with clozapine. Interestingly, clozapine reversed protein changes induced by MK
      801. The treatment of cell cultures with neural transmission agonists and
      antagonists might provide useful insights about psychiatric disorders.

PMID- 21088846
TI  - Characterization of TTAGG telomeric repeats, their interstitial occurrence and
      constitutively active telomerase in the mealybug Planococcus lilacinus
      (Homoptera; Coccoidea).
AB  - We confirmed the occurrence of the insect TTAGG telomeric repeats in the mealybug
      Planococcus lilacinus, a radiation-resistant coccid, by single primer polymerase
      chain reaction (PCR) and Southern hybridization. Analysis of Bal31 nuclease
      digested DNA by Southern hybridization and chromosomes by FISH suggests that
      these repeats occur mainly at the ends of the chromosomes. However, sequence
      analysis of the PCR products of TTAGG-associated sequences from genomic DNA
      showed their interstitial occurrence and association with certain unrelated low
      copy repeats. Because of their shorter length, the interstitial TTAGG sequences
      were detectable by primed in situ hybridizations but not by FISH. Analysis of
      chromosomes recovered after irradiation by fluorescent in situ hybridization
      suggested acquisition of TTAGG repeats at a majority of the healed ends. We also
      observed mild telomerase activity in unirradiated insects which was further
      enhanced after irradiation. Taken together, these results suggest that the
      mealybug has an efficient mechanism of formation of TTAGG repeats at radiation
      induced chromosome ends and constitutively active telomerase may be a feature
      associated with rapid recovery of chromosome ends damaged by ionizing radiation.

PMID- 21088848
TI  - Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti
      AChR antibodies.
AB  - Patients with myasthenia gravis (MG) with antibodies to muscle-specific receptor
      tyrosine kinase (MuSK) differ from acetylcholine receptor (AChR)-positive MG
      patients, as they frequently present with severe oculobulbar muscle weakness or
      with neck, shoulder, and respiratory muscle involvement. The neuromuscular
      junction (NMJ) has been confirmed to be the main target of both AChR- and MuSK
      MG. However, histopathological investigation disclosed that muscle fiber atrophy
      was prevalent in AChR-MG, whereas mild myopathic changes and mitochondrial
      abnormalities were more frequently observed in MuSK-MG. As the pathogenetic
      mechanism in MuSK-MG remains unclear, this study investigated the submicroscopic
      pattern of muscle histopathology to establish a possible correlation between
      clinical involvement and subcellular morphological findings. Muscle biopsies from
      seven MuSK-MG patients and from seven patients with AChR-MG were analyzed by
      transmission electron microscopy. Myopathic and mitochondrial abnormalities were
      more prominent in MuSK-MG and show giant, swollen, and degenerated mitochondria
      with fragmented cristae. The most common changes in AChR-MG muscles were fiber
      atrophy, myofibrillar disarray, and Z-line streaming, consistent with mild
      neurogenic abnormalities. A different pathogenetic mechanism is emerging in MuSK
      MG compared to AChR-MG. Mitochondrial abnormalities seem to be more prominent in
      MuSK-MG, whereas neurogenic atrophy is observed in AChR-MG.

PMID- 21088849
TI  - A tool to improve pre-selection for deep brain stimulation in patients with
      Parkinson's disease.
AB  - Determining the eligibility of patients with Parkinson's disease (PD) for deep
      brain stimulation (DBS) can be challenging for general (non-specialised)
      neurologists. We evaluated the use of an online screening tool (Stimulus) that
      aims to support appropriate referral to a specialised centre for the further
      evaluation of DBS. Implementation of the tool took place via an ongoing European
      multicentre educational programme, currently completed in 15 DBS centres with 208
      referring neurologists. Use of the tool in daily practice was monitored via an
      online data capture programme. Selection decisions of patients referred with the
      assistance of the Stimulus tool were compared to those of patients outside the
      screening programme. Three years after the start of the programme, 3,128 patient
      profiles had been entered. The intention for referral was made for 802 patients
      and referral intentions were largely in accordance with the tool recommendations.
      Follow-up at 6 months showed that actual referral took place in only 28%,
      predominantly due to patients' reluctance to undergo brain surgery. In patients
      screened with the tool and referred to a DBS centre, the acceptance rate was 77%,
      significantly higher than that of the unscreened population (48%). The tool
      showed a sensitivity of 99% and a specificity of 12% with a positive and negative
      predictive value of 79 and 75%, respectively. The Stimulus tool is useful in
      assisting general neurologists to identify appropriate candidates for DBS
      consideration. The principal reason for not referring potentially eligible
      patients is their reluctance to undergo brain surgery.

PMID- 21088850
TI  - Ocular complications of external carotid circulation embolization: report of two
      cases.

PMID- 21088851
TI  - Characterization of Bangerter filter effect in mild and moderate anisometropic
      amblyopia: predictive factors for the visual outcome.
AB  - PURPOSE: To evaluate the outcome achieved by using Bangerter filters in cases of
      mild and moderate anisometropic amblyopia, and to define the predictive factors
      for the final visual outcome. METHODS: Prospective study comprising 62 children
      (age range 3-11 years) with unilateral amblyopia associated with myopic or
      hyperopic anisometropia. In all cases, the use of Bangerter filters were
      prescribed for amblyopia treatment due to the unsuccessful outcome with
      refractive correction. The prescribed filter always induced a visual acuity
      reduction in the non-amblyopic eye of 2 lines below the BSCVA of the amblyopic
      eye. A follow-up of 12 months was completed. RESULTS: A statistically significant
      improvement in visual acuity was observed at 3 months in both groups, amblyopic
      and non-amblyopic eyes (p < 0.01). At 6, 9 and 12 months, additional small but
      statistically significant improvements in visual acuity were detected only in the
      amblyopic group (p <= 0.02). Filter density had to be changed during the follow
      up in a total of 22 eyes (35.5%). A significant correlation of the visual acuity
      with the baseline interocular visual acuity difference was found at 3 months (r =
      0.44, p < 0.01), but not at the end of the follow-up (r = 0.12, p = 0.36).
      Multiple linear regression analysis revealed that the final visual outcome was
      significantly correlated with the baseline visual acuity, sphere and the
      difference in visual acuity between eyes (R2: 0.42, p < 0.01). CONCLUSIONS:
      Bangerter filters are useful for treating mild or moderate amblyopia due to
      anisometropia, but ocular dominance inversion should be maintained during
      treatment for obtaining an optimized outcome.

PMID- 21088853
TI  - Adenoma of the nonpigmented ciliary epithelium presenting with recurrent
      iridocyclitis: unique expression of glial fibrillary acidic protein.

PMID- 21088854
TI  - Expression of peripherin in human cochlea.
AB  - The organ of Corti contains two different types of auditory receptors; the inner
      (IHCs) and outer (OHCs) hair cells. This dualism is further represented in their
      innervation, IHCs being innervated by type I neurons, and OHCs by type II neurons
      (in man, named small ganglion cells). Two efferent systems are also present.
      Here, we have analyzed the expression of the 57-kDa neuron-specific intermediate
      filament protein peripherin (PP) in human cochlea. In the human organ of Corti,
      PP seems to be specifically expressed in OHC afferents. Small or type II spiral
      ganglion cell bodies also intensely express PP. Thus, PP can be used as a marker
      for the characterization of the innervation of the OHC system in man.

PMID- 21088855
TI  - Biological roles of host defense peptides: lessons from transgenic animals and
      bioengineered tissues.
AB  - Host defense peptides (HDPs) have long been recognized as microbicidal agents,
      but their roles as modulators of innate and adaptive immunity have only more
      recently been appreciated. The study of transgenic animal and tissue models has
      provided platforms to improve our understanding of the immune modulatory
      functions of HDPs. Here, the characterization of transgenic animals or tissue
      models that over-express and/or are deficient for specific HDPs is reviewed. We
      also attempt to reconcile this data with evidence from human studies monitoring
      HDP expression at constitutive levels and/or in conjunction with inflammation,
      infection models, or disease states. We have excluded activities ascribed to HDPs
      derived exclusively from in vitro experiments. An appreciation of the way that
      HDPs promote innate immunity or influence the adaptive immune response is
      necessary in order to exploit their therapeutic or adjuvant potential and to open
      new perspectives in understanding the basis of immunity. The potential
      applications for HDPs are discussed.

PMID- 21088856
TI  - Isolation of oogonia from ovaries of the sea urchin Strongylocentrotus nudus.
AB  - The presence of oogonia in the ovaries of adult females is typical in species
      with a broadcast spawning reproductive strategy, including invertebrates and
      lower vertebrates. In sea urchins, difficulties in the study of oogonia arise
      from the small number of these cells and the lack of specific markers for their
      identification. Therefore, more reliable methods are needed for identifying and
      manipulating oogonial cells in quantities sufficient for experimentation.
      Homologs of the DEAD-box RNA helicase vasa expressed in germline cells have been
      proposed for use as markers to detect germline cells in diverse species. We have
      developed a method for the isolation of sea urchin oogonia by using
      immunocytochemistry with vasa antibodies, together with reverse transcription and
      the polymerase chain reaction to detect the expression of Sp-vasa and Sp-nanos2
      homologs and a morphological approach to identify germline cells in sea urchin
      ovaries and cell fractions isolated from the ovarian germinal epithelium. This
      method has allowed us to obtain 15%-18% of small oogonia with 70%-75% purity from
      the total amount of isolated germ cells. Our findings represent the first
      methodological basis for obtaining cell populations containing sea urchin
      oogonia; this method might be useful as a tool for further investigations of the
      early stages of sea urchin oogenesis.

PMID- 21088857
TI  - A comparison of surgical outcomes between endoscopic and robotically assisted
      thyroidectomy: the authors' initial experience.
AB  - BACKGROUND: The gasless, transaxillary endoscopic thyroidectomy (GTET) offers a
      distinct advantage over the conventional open operation by leaving no visible
      neck scar, and in an attempt to improve its ergonomics and surgical outcomes, the
      robotically assisted thyroidectomy (RAT) was introduced. The RAT uses the same
      endoscopic route as the GTET but with the assistance of the da Vinci S robotic
      system. Excellent results for RAT have been reported, but it remains unclear
      whether RAT offers any potential benefits over GTET. METHODS: From June to
      December 2009, 46 patients underwent endoscopic thyroidectomy. Of these patients,
      39 had surgery without the robot (GTET) and 7 had surgery with the robot (RAT).
      Demographics, surgical indications, operative findings, and postoperative
      outcomes were compared between the two groups. All the patients were followed up
      for at least 6 months after surgery. RESULTS: Patient demographics, surgical
      indications, and extent of resection were similar between the two groups. The
      median total procedure time was significantly longer for RAT (149 min) than for
      GTET (100 min; p=0.018), but the contralateral recurrent laryngeal nerve was more
      likely to identified in RAT (100%) than in GTET (42.9%; p=0.070). On the average,
      GTET needed one more surgical assistant than RAT (1 vs. 0; p<0.001). The median
      pain score on postoperative day 0 was significantly higher with RAT than with
      GTET (4 vs. 2; p=0.025) but was similar on day 1. Blood loss, hospital stay, and
      surgical complications were similar in the two groups. CONCLUSIONS: In our early
      experience, adding the da Vinci S robot to GTET increased the total procedure
      time and resulted in a higher pain score on day 0 but eliminated the need for any
      surgical assistant at the time of the operation.

PMID- 21088858
TI  - Development and pilot testing of a communication aid to assist clinicians to
      communicate with women diagnosed with ductal carcinoma in situ (DCIS).
AB  - PURPOSE: The literature highlights the confusion amongst women diagnosed with
      ductal carcinoma in situ (DCIS) about aspects of their disease and treatment and
      the wide variation in how doctors communicate about DCIS. The DCIS communication
      aid (CA) was developed to assist clinicians to communicate with women diagnosed
      with DCIS and to improve women's understanding about their disease, prognosis and
      treatment options. This study aimed to assess patient and clinician perceptions
      of the CA. METHODS: The CA included information and diagrams about key aspects of
      the diagnosis, prognosis, treatment and support. It was designed to be used in
      clinical consultations and taken home after the consultation. Australian women
      with DCIS (n = 18) participated in structured interviews and clinicians (n = 7),
      including surgeons and radiation oncologists, completed surveys to assess their
      perceptions of the CA. Main outcome measures included satisfaction with the
      content, design and diagrams in the CA, and perceptions of the benefits of the CA
      and its impact on doctor-patient communication. RESULTS: All clinicians and women
      with DCIS reported that the CA would assist communication and help women
      understand their diagnosis. CONCLUSIONS: This is the first intervention designed
      to decrease the confusion amongst women with DCIS and improve doctor-patient
      communication in this area. This study highlights that interventions such as the
      DCIS communication aid may be a valuable resource for clinicians and women with
      DCIS. This study also highlights key communication challenges relating to DCIS.

PMID- 21088859
TI  - A child with influenza A (H1N1)-associated myocarditis rescued by extracorporeal
      membrane oxygenation.
AB  - A 6-year-old boy had cold-like symptoms and was diagnosed with influenza A at a
      clinic. Administration of oseltamivir and azithromycin did not improve the
      symptoms. He was referred to our hospital and was diagnosed with H1N1 pneumonia.
      The patient required ventilator support. However, hypoxia and hypercapnia were
      uncontrollable. To oxygenate and reduce the carbon dioxide concentration, veno
      venous extracorporeal membrane oxygenation (ECMO) was applied 24 h after
      admission. We established outflow via the right internal jugular vein and inflow
      via the right femoral vein. Six hours later, an electrical storm of ventricular
      fibrillation occurred, probably due to influenza myocarditis. Chest compression
      was started immediately. Both cardioversion and medication were ineffective in
      treating the electrical storm. Therefore, we decided to switch the veno-venous
      ECMO to veno-arterial ECMO to maintain systemic flow. During chest compression, a
      6-mm graft was anastomosed to the left common femoral artery, and an outflow tube
      was connected to the graft. Consequently, veno-arterial ECMO was established via
      outflow through the left common femoral artery and inflow through both the right
      jugular vein and right femoral vein. Veno-arterial ECMO terminated the electrical
      storm, and cardiac output improved. Veno-arterial ECMO was provided for 107 h,
      and was then replaced by veno-venous ECMO. Forty-three hours later, veno-venous
      ECMO was discontinued. The patient was successfully weaned from the mechanical
      ventilator on the 9th day after admission. Unfortunately, spinal infarction
      appeared as a complication. The patient was discharged from the hospital on the
      86th day, and has now returned to primary school.

PMID- 21088860
TI  - Infrapatellar bursitis in children with juvenile idiopathic arthritis: a case
      series.
AB  - Children with juvenile idiopathic arthritis (JIA) may infrequently present with
      localized anterior knee pain or swelling, in addition to generalize knee pain
      induced by JIA. We report five cases of deep infrapatellar bursitis in children
      with JIA. The clinical features, radiological findings, management, and outcome
      of five children with JIA and deep infrapatellar bursitis are reviewed. Three
      boys and two girls with a mean age of 9.8 years (range 6-14 years) were reviewed.
      Four children had persistent oligoarticular JIA, and one child had extended
      oligoarticular JIA. The presentation of deep infrapatellar bursitis was variable.
      In only one patient was the bursal swelling painful. Knee magnetic resonance
      imaging (MRI) was performed in four patients and demonstrated coexistent knee
      joint synovitis in three. Treatment included targeted corticosteroid injections
      into the deep infrapatellar bursa in two cases with complete resolution. One case
      was treated with corticosteroid injection by an outside health care provider with
      poor clinical response. Two cases are being treated with non-steroidal anti
      inflammatory drugs and methotrexate. Deep infrapatellar bursitis can occur as an
      isolated finding or concurrently with knee joint synovitis in patients with JIA.
      Awareness of this entity is important because direct injection of the bursa may
      be needed for treatment, as the bursa does not communicate with the knee joint.
      Furthermore, when bursitis is suspected in JIA, MRI can be helpful to confirm the
      diagnosis, detect concurrent knee joint synovitis, and exclude other pathologies.

PMID- 21088861
TI  - In vitro antibacterial activity of doripenem against clinical isolates from
      French teaching hospitals: proposition of zone diameter breakpoints.
AB  - The aims of the study were to determine the in vitro activity of doripenem, a new
      carbapenem, against a large number of bacterial pathogens and to propose zone
      diameter breakpoints for clinical categorization in France according to the
      European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum
      inhibitory concentration (MIC) breakpoints. The MICs of doripenem were determined
      by the broth microdilution method against 1,547 clinical isolates from eight
      French hospitals. The disk diffusion test was performed (10-MUg discs) according
      to the Comite de l'Antibiogramme de la Societe Francaise de Microbiologie (CASFM)
      method. The MIC(50/90) (mg/L) values were as follows: methicillin-susceptible
      Staphylococcus aureus (MSSA) (0.03/0.25), methicillin-resistant Staphylococcus
      aureus (MRSA) (1/2), methicillin-susceptible coagulase-negative staphylococci
      (MSCoNS) (0.03/0.12), methicillin-resistant coagulase-negative staphylococci
      (MRCoNS) (2/8), Streptococcus pneumoniae (0.016/0.25), viridans group
      streptococci (0.016/2), beta-hemolytic streptococci (<=0.008/<=0.008),
      Enterococcus faecalis (2/4), Enterococcus faecium (128/>128), Enterobacteriaceae
      (0.06/0.25), Pseudomonas aeruginosa (0.5/8), Acinetobacter baumannii (0.25/2),
      Haemophilus influenzae (0.12/0.25), and Moraxella catarrhalis (0.03/0.06).
      According to the regression curve, the zone diameter breakpoints were 24 and 19
      mm for MICs of 1 and 4 mg/L, respectively. This study confirms the potent in
      vitro activity of doripenem against Pseudomonas aeruginosa, Acinetobacter,
      Enterobacteriaceae, MSSA, MSCoNS, and respiratory pathogens. According to the
      EUCAST MIC breakpoints (mg/L) <=1/>4 for Enterobacteriaceae, Pseudomonas
      aeruginosa, and Acinetobacter, and <=1/>1 for streptococci, pneumococci, and
      Haemophilus, the zone diameter breakpoints could be (mm) >=24/<19 and >=24/<24,
      respectively.

PMID- 21088864
TI  - Morphogenetic processes in animals and plants.

PMID- 21088863
TI  - Microbeam radiosurgery using synchrotron-generated submillimetric beams: a new
      tool for the treatment of brain disorders.
AB  - Since its advent during the mid-twentieth century, radiosurgery has undergone a
      steady evolution. Gamma Knife and linear accelerator based systems using rigid
      frames preceded the development of frameless devices. The present report
      describes the development of microbeam radiosurgery, a technique which uses
      submillimetric beams of radiation to treat disease. Typically, the technique is
      employed using parallel arrays of beams delivered via a high-fluence synchrotron
      source. Beam widths between 20 and 950 MUm have been used with the majority of
      studies utilizing beam widths less than 100 MUm. In addition to its high
      precision, the technique allows users to take advantage of two unique properties
      of microbeams. The first is a remarkable tolerance of healthy tissue to
      microbeams delivered at doses up to several hundred grays, while at the same
      time, tumors are highly susceptible to the lethal effects of microbeams.
      Together, these findings allow for a "preferential tumoricidal effect" beyond the
      typical dose-volume relationship. Although only used in animal experiments so
      far, we explore the hypothetical clinical role of microbeam radiosurgery which
      may be feasible in the near future. In addition to the treatment of traditional
      radiosurgery targets such as malignancies and vascular malformations, microbeams
      may allow the non-invasive treatment of functional disease such as movement
      disorders, epilepsy, and mental illness.

PMID- 21088862
TI  - Comparison between cold water immersion therapy (CWIT) and light emitting diode
      therapy (LEDT) in short-term skeletal muscle recovery after high-intensity
      exercise in athletes--preliminary results.
AB  - In the last years, phototherapy has becoming a promising tool to improve skeletal
      muscle recovery after exercise, however, it was not compared with other
      modalities commonly used with this aim. In the present study we compared the
      short-term effects of cold water immersion therapy (CWIT) and light emitting
      diode therapy (LEDT) with placebo LEDT on biochemical markers related to skeletal
      muscle recovery after high-intensity exercise. A randomized double-blind placebo
      controlled crossover trial was performed with six male young futsal athletes.
      They were treated with CWIT (5 degrees C of temperature [SD +/-1 degrees ]),
      active LEDT (69 LEDs with wavelengths 660/850 nm, 10/30 mW of output power, 30 s
      of irradiation time per point, and 41.7 J of total energy irradiated per point,
      total of ten points irradiated) or an identical placebo LEDT 5 min after each of
      three Wingate cycle tests. Pre-exercise, post-exercise, and post-treatment
      measurements were taken of blood lactate levels, creatine kinase (CK) activity,
      and C-reactive protein (CRP) levels. There were no significant differences in the
      work performed during the three Wingate tests (p > 0.05). All biochemical
      parameters increased from baseline values (p < 0.05) after the three exercise
      tests, but only active LEDT decreased blood lactate levels (p = 0.0065) and CK
      activity (p = 0.0044) significantly after treatment. There were no significant
      differences in CRP values after treatments. We concluded that treating the leg
      muscles with LEDT 5 min after the Wingate cycle test seemed to inhibit the
      expected post-exercise increase in blood lactate levels and CK activity. This
      suggests that LEDT has better potential than 5 min of CWIT for improving short
      term post-exercise recovery.

PMID- 21088865
TI  - Letter to the editor concerning "An automated blood vessel segmentation algorithm
      using histogram equalization and automatic threshold selection".

PMID- 21088866
TI  - A role for MT1-MMP as a cell death sensor/effector through the regulation of
      endoplasmic reticulum stress in U87 glioblastoma cells.
AB  - Recent findings in cell death signalling show that membrane type 1 matrix
      metalloproteinase (MT1-MMP), an MMP known for its involvement in cancer cell
      invasion and metastasis, can act as a "bioswitch" in the invasion versus cell
      death decision in brain tumour cells. Given that the endoplasmic reticulum (ER)
      is a subcellular compartment involved in metabolic control and cell death
      signalling and that cytoskeleton disruption, as encountered during cancer cell
      invasion, can lead to ER stress, we questioned whether MT1-MMP contributes to ER
      stress. We found that MT1-MMP gene silencing or pharmacological inhibition of
      vesicular trafficking with Brefeldin-A abrogated MT1-MMP cell surface-mediated
      proMMP-2 activation by the lectin Concanavalin-A (ConA) in U87 glioblastoma
      cells. ConA, also known to trigger the expression of pro-inflammatory
      cyclooxygenase (COX)-2 through MT1-MMP signalling from the plasma membrane,
      failed to do so when MT1-MMP was prevented from reaching the cell surface by
      Brefeldin-A. Gene silencing of MT1-MMP antagonized the expression of ConA-induced
      COX-2 and of the ER stress marker glucose-related protein 78 (GRP78), further
      suggesting that plasma membrane localization of MT1-MMP contributes to signalling
      ER stress. MT1-MMP maturation, which partially occurs during its trafficking from
      the ER to the plasma membrane, showed correlation of the 60 kDa MT1-MMP with
      GRP78 expression. Finally, Brefeldin-A treatment of glioblastoma cells led to Akt
      dephosphorylation; this effect was reversed when MT1-MMP was silenced.
      Collectively, our results provide a molecular rationale for a new role for MT1
      MMP in the regulation of cancer cell death processes through ER stress
      signalling.

PMID- 21088867
TI  - Aspergillus as a multi-purpose cell factory: current status and perspectives.
AB  - Aspergilli have a long history in biotechnology as expression platforms for the
      production of food ingredients, pharmaceuticals and enzymes. The achievements
      made during the last years, however, have the potential to revolutionize
      Aspergillus biotechnology and to assure Aspergillus a dominant place among
      microbial cell factories. This mini-review will highlight most recent
      breakthroughs in fundamental and applied Aspergillus research with a focus on new
      molecular tools, techniques and products. New trends and concepts related to
      Aspergillus genomics and systems biology will be discussed as well as the
      challenges that have to be met to integrate omics data with metabolic engineering
      attempts.

PMID- 21088868
TI  - Rational design of styrene monooxygenase mutants with altered substrate
      preference.
AB  - Styrene monooxygenase catalyzes the enantioselective epoxidation of styrene but
      displays significantly decreased activity toward styrene derivatives with an
      alpha- or beta-substituent. Based on the X-ray crystal structure of the oxygenase
      subunit of styrene monooxygenase, molecular docking of alpha-ethylstyrene was
      performed to identify adjacent residues. Four amino acid substitutions (R43A,
      L44A, L45A, and N46A) were introduced into the enzyme by site-directed
      mutagenesis. All four mutations led to a change of substrate preference. The
      mutant L45A, in particular, exhibited an altered substrate preference toward the
      bulkier substrate alpha-ethylstyrene.

PMID- 21088869
TI  - Oxidative stress in fungal fermentation processes: the roles of alternative
      respiration.
AB  - Filamentous fungi are arguably the most industrially important group of
      microorganisms. Production processes involving these simple eukaryotes are often
      highly aerobic in nature, which implies these cultures are routinely subject to
      oxidative stress. Despite this, little is known about how filamentous fungi cope
      with high levels of oxidative stress as experienced in fermenter systems. More
      surprisingly, much of our knowledge of oxidative stress responses in fungi comes
      from environmental or medical studies. Here, the current understanding of
      oxidative stress effects and cellular responses in filamentous fungi is
      critically discussed. In particular the role of alternative respiration is
      evaluated, and the contributions of the alternative oxidase and alternative
      dehydrogenases in defence against oxidative stress, and their profound influence
      on fungal metabolism is critically examined. Finally, the importance of further
      research which would underpin a less empirical approach to optimising fungal
      strains for the fermenter environment is emphasised.

PMID- 21088870
TI  - Conformational study of bovine lactoferricin in membrane-micking conditions by
      molecular dynamics simulation and circular dichroism.
AB  - Lactoferricins are potent antimicrobial peptides released by pepsin cleavage of
      Lactoferrins. Bovine Lactoferricin (LfcinB) has higher activity than the intact
      bovine Lactoferrin, and is the most active among the other Lactoferricins of
      human, murine and caprine origin. In the intact protein the fragment
      corresponding to LfcinB is in an helical conformation, while in water LfcinB
      adopts an amphipathic beta-hairpin structure. However, whether any of these
      structural motifs is the antibacterial active conformation, i.e., the one
      interacting with bacterial membrane components, remains to be seen. Here we
      present Circular Dichroism (CD) spectra and Molecular Dynamics (MD) simulations
      indicating that in membrane-mimicking solvents the LfcinB adopts an amphipathic
      beta-hairpin structure similar to that observed in water, but differing in the
      dynamic behavior of the side-chains of the two tryptophan residues. In the
      membrane-mimicking solvent these side-chains show a high propensity to point
      towards the hydrophobic environment, rather than being in the hydrophobic core as
      seen in water, while the backbone preserves the hairpin conformation as found in
      water. These results suggest that the tryptophans might act as anchors pulling
      the stable, solvent-invariant hairpin structure into the membrane.

PMID- 21088871
TI  - Endogenous ADP-ribosylation of elongation factor-2 by interleukin-1beta.
AB  - Eukaryotic elongation factor-2 (eEF-2) catalyses the motion of the growing
      peptide chain relative to the mRNA at the ribosomes during protein synthesis.
      This highly conserved G-protein is the specific target of two lethal bacterial
      toxins, Pseudomonas aeruginosa exotoxin A and diphtheria toxin. These toxins
      exert their detrimental action by ADP-ribosylating a biologically unique
      posttranslationally modified histidine residue (diphthamide(715)) within eEF-2,
      thus inactivating the enzyme. Diphthamide(715) is also the target of endogenous
      (mono) ADP-ribosyl transferase activity. In this article, we report the first
      known activator of endogenous ADP-ribosylation of eEF-2, interleukin-1beta (IL
      1beta). Thereby, systemic inflammatory processes may link to protein synthesis
      regulation.

PMID- 21088872
TI  - The use of the SAEM algorithm in MONOLIX software for estimation of population
      pharmacokinetic-pharmacodynamic-viral dynamics parameters of maraviroc in
      asymptomatic HIV subjects.
AB  - Using simulated viral load data for a given maraviroc monotherapy study design,
      the feasibility of different algorithms to perform parameter estimation for a
      pharmacokinetic-pharmacodynamic-viral dynamics (PKPD-VD) model was assessed. The
      assessed algorithms are the first-order conditional estimation method with
      interaction (FOCEI) implemented in NONMEM VI and the SAEM algorithm implemented
      in MONOLIX version 2.4. Simulated data were also used to test if an effect
      compartment and/or a lag time could be distinguished to describe an observed
      delay in onset of viral inhibition using SAEM. The preferred model was then used
      to describe the observed maraviroc monotherapy plasma concentration and viral
      load data using SAEM. In this last step, three modelling approaches were
      compared; (i) sequential PKPD-VD with fixed individual Empirical Bayesian
      Estimates (EBE) for PK, (ii) sequential PKPD-VD with fixed population PK
      parameters and including concentrations, and (iii) simultaneous PKPD-VD. Using
      FOCEI, many convergence problems (56%) were experienced with fitting the
      sequential PKPD-VD model to the simulated data. For the sequential modelling
      approach, SAEM (with default settings) took less time to generate population and
      individual estimates including diagnostics than with FOCEI without diagnostics.
      For the given maraviroc monotherapy sampling design, it was difficult to separate
      the viral dynamics system delay from a pharmacokinetic distributional delay or
      delay due to receptor binding and subsequent cellular signalling. The preferred
      model included a viral load lag time without inter-individual variability.
      Parameter estimates from the SAEM analysis of observed data were comparable among
      the three modelling approaches. For the sequential methods, computation time is
      approximately 25% less when fixing individual EBE of PK parameters with omission
      of the concentration data compared with fixed population PK parameters and
      retention of concentration data in the PD-VD estimation step. Computation times
      were similar for the sequential method with fixed population PK parameters and
      the simultaneous PKPD-VD modelling approach. The current analysis demonstrated
      that the SAEM algorithm in MONOLIX is useful for fitting complex mechanistic
      models requiring multiple differential equations. The SAEM algorithm allowed
      simultaneous estimation of PKPD and viral dynamics parameters, as well as
      investigation of different model sub-components during the model building
      process. This was not possible with the FOCEI method (NONMEM version VI or
      below). SAEM provides a more feasible alternative to FOCEI when facing lengthy
      computation times and convergence problems with complex models.

PMID- 21088873
TI  - Examining the criminal history and future offending of child pornography
      offenders: an extended prospective follow-up study.
AB  - We examined police occurrence and criminal records data for a sample of 201
      registered male child pornography offenders originally reported by Seto and Eke
      (Sex Abus J Res Treat 17:201-210, 2005), extending the average follow-up time for
      this sample to 5.9 years. In addition, we obtained the same data for another 340
      offenders, increasing our full sample to 541 men, with a total average follow-up
      of 4.1 years. In the extended follow-up of the original sample, 34% of offenders
      had new charges for any type of reoffense, with 6% charged with a contact sexual
      offense against a child and an additional 3% charged with historical contact sex
      offenses (i.e., previously undetected offenses). For the full sample, there was a
      32% any recidivism rate; 4% of offenders were charged with new contact sex
      offences, an additional 2% of offenders were charged with historical contact sex
      offenses and 7% of offenders were charged with a new child pornography offense.
      Predictors of new violent (including sexual contact) offending were prior offense
      history, including violent history, and younger offender age. Approximately a
      quarter of the sample was sanctioned for a failure on conditional release; in
      half of these failures, the offenders were in contact with children or used the
      internet, often to access pornography again.

PMID- 21088874
TI  - Ethnicity, perceived pubertal timing, externalizing behaviors, and depressive
      symptoms among black adolescent girls.
AB  - An accumulation of research evidence suggests that early pubertal timing plays a
      significant role in girls' behavioral and emotional problems. If early pubertal
      timing is a problematic event, then early developing Black girls should manifest
      evidence of this crisis because they tend to be the earliest to develop compared
      to other girls from different racial and ethnic groups. Given the inconsistent
      findings among studies using samples of Black girls, the present study examined
      the independent influence of perceived pubertal timing and age of menarche on
      externalizing behaviors and depressive symptoms in a nationally representative
      sample of Black girls (412 African American and 195 Caribbean Black; M = 15
      years). Path analysis results indicated that perceived pubertal timing effects on
      externalizing behaviors were moderated by ethnic subgroup. Caribbean Black girls'
      who perceived their development to be early engaged in more externalizing
      behaviors than Caribbean Black girls' who perceived their development to be
      either on-time or late. Age of menarche did not significantly predict Black
      girls' externalizing behaviors and depressive symptoms. The onset of menarche
      does not appear to be an important predictor of Black girls' symptoms of
      externalizing behavior and depression. These findings suggest ethnic subgroup and
      perceived pubertal timing are promising factors for better understanding the
      adverse effects of early perceived pubertal timing among Black girls.

PMID- 21088875
TI  - Examining the light and dark sides of emerging adults' identity: a study of
      identity status differences in positive and negative psychosocial functioning.
AB  - Identity is a critical developmental task during the transition to adulthood in
      Western societies. The purpose of the present study was to evaluate an
      empirically based, cluster-analytic identity status model, to examine whether all
      four of Marcia's identity statuses (diffusion, foreclosure, moratorium, and
      achievement) would emerge empirically, and to identify different patterns of
      identity formation among American college-attending emerging adults. An
      ethnically diverse sample of 9,034 emerging-adult students (73% female; mean age
      19.73 years) from 30 U.S. universities completed measures of identity exploration
      (ruminative, in breadth, and in depth) and commitment (commitment making and
      identification with commitment), identity synthesis and confusion, positive and
      negative psychosocial functioning, and health-compromising behaviors. The
      identity status cluster solution that emerged provided an adequate fit to the
      data and included all four of Marcia's original identity statuses, along with
      Carefree Diffusion and Undifferentiated statuses. Results provided evidence for
      concurrent validity, construct validity, and practical applicability of these
      statuses. Implications for identity research are discussed.

PMID- 21088876
TI  - Other-sex friendships in late adolescence: risky associations for substance use
      and sexual debut?
AB  - Adolescents' friendships with other-sex peers serve important developmental
      functions, but they may also facilitate engagement in problem behavior. This
      study examines the unique contributions of other-sex friendships and friends'
      behavior to alcohol use, smoking, and initiation of sexual intercourse among late
      adolescent girls and boys. A total of 320 adolescents (53% girls; 33%
      racial/ethnic minorities) provided sociometric nominations of friendships
      annually in grades 10-12. Friendship networks were derived using social network
      analysis in each grade. Adolescents and their friends also reported on their
      alcohol use, smoking, and sexual debut at each assessment. After controlling for
      demographics, previous problem behavior, and friends' behavior, other-sex
      friendships in 10th grade were associated with initiation of smoking among girls
      over the following year, and other-sex friendships in 11th grade were linked with
      lower levels of subsequent alcohol use among boys. Additionally, friends' smoking
      and sexual experience in 10th grade predicted the same behaviors for all
      adolescents over the following year. Other-sex friendships thus appear to serve
      as a risk context for adolescent girls' smoking and a protective context for
      adolescent boys' drinking. Promoting mixed-gender activities and friendships
      among older high school students may be helpful in reducing males' alcohol use,
      but may need to incorporate additional components to prevent increases in
      females' smoking.

PMID- 21088877
TI  - Brain energy metabolism parameters in an animal model of diabetes.
AB  - A growing body of evidence has indicated that altered mitochondrial function may
      be involved in mechanism for the development of diabetic complications. Thus, we
      investigated whether animal model of diabetes induced by alloxan alters energy
      metabolism parameters. Wistar rats received one single injection of alloxan (250
      mg/kg) and after 15 days we evaluated mitochondrial respiratory chain complexes
      I, II, II-III and IV, creatine kinase and citrate synthase activities in
      prefrontal cortex, hippocampus and striatum. We observed that animal model of
      diabetes induced by alloxan increased complexes I and IV activities in
      hippocampus, complexes II and II-III activities in prefrontal cortex and striatum
      and complex IV in prefrontal cortex; however decreased complex IV activity in
      striatum. Moreover, diabetes rats decreased creatine kinase activity in striatum
      and increased citrate synthase activity in hippocampus. In conclusion, this study
      indicates that the alteration in mitochondrial function is probably involved in
      the pathophysiology of diabetes.

PMID- 21088878
TI  - Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre
      diabetic rats.
AB  - Cardiovascular risk is closely associated with insulin resistance and type 2
      diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel
      approach to treat this disease. The aims of this study was therefore to use an
      animal model to determine whether (i) pre-treatment of obese, insulin resistant
      but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart
      from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in
      such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10
      mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject
      hearts to ischaemia/reperfusion to determine infarct size, functional recovery
      and post-ischaemic activation of proteins associated with cardiac protection.
      Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity.
      Other assessments included body weight, intra-peritoneal fat weight, insulin and
      GLP-1 levels as well as histological evaluation of the pancreata. Results showed
      that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed
      animals. They presented with elevated plasma insulin levels and lower GLP-1
      levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size
      development in hearts from DIO rats after ischaemia/reperfusion accompanied by
      activation of cardioprotective kinases. GLP-1 levels were elevated and plasma
      insulin levels lower after treatment. In addition, the beta-cell to alpha-cell
      ratio of the pancreas was improved. We conclude that treatment with PFK275-055
      for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated
      GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

PMID- 21088879
TI  - A shared egg donor program: which is the minimum number of oocytes to be
      allocated?
AB  - PURPOSE: To evaluate which is the minimum number of oocytes to be allocated to
      each recipient in a shared egg donor program. METHODS: We analyzed 953 recipients
      that received at least 4 metaphase II (MII) oocytes in the period 2006-2008. We
      retrospectively divided the recipients according to the number of MII oocytes
      actually received. RESULTS: No statistically significant differences were found
      among the analyzed strata in clinical pregnancy rate (A:43.7%; B:45.6%; C:48.6%;
      D:45.5%; E:53%, P=NS) and miscarriage rate. However, the rate of top quality
      transferred embryos, and the embryo freezing rate were significantly higher among
      those recipients that received 7 or more mature eggs. CONCLUSIONS: After a large
      sample was analyzed, no significant differences in fresh embryo transfer outcome
      were encountered when a different number of oocytes was allocated. A minimum of 4
      MII oocytes seems to achieve satisfactory pregnancy rates in our shared egg donor
      program.

PMID- 21088880
TI  - Adolescent family adversity and mental health problems: the role of adaptive self
      regulation capacities. The TRAILS study.
AB  - Adolescent family adversity is a considerable adaptive challenge in an
      increasingly turbulent developmental period. Using data from a prospective
      population cohort of 2230 Dutch adolescents, we tested risk-buffering
      interactions between adolescent family adversity and self-regulation capacities
      on mental health. We used two adaptive self-regulation capacities that could
      allow adolescents to manage relatively well with family adversity: (1) parent
      reported effortful control, and (2) an attentional flexibility (in this case, set
      shifting) task. Adolescent family adversity was associated with internalizing
      problems and externalizing problems. The risk-buffering effects of effortful
      control were found for externalizing problems but not for internalizing problems.
      There were no risk-buffering effects of attentional flexibility on both types of
      mental health problems. Effortful control is likely to benefit adolescents'
      ability to channel their frustrations in adaptive ways in the presence of family
      adversity. Additionally, (attentional) set-shifting tasks might have a limited
      predictive value for risk-buffering research.

PMID- 21088881
TI  - Ion channels and neuroendocrine cells: old partners in the investigation of each
      other's function. Commentary on the "ion channels" chapter.

PMID- 21088882
TI  - Commentary on chapters 'clinical and developmental aspects' and 'stress responses
      of the adrenal medulla'.

PMID- 21088883
TI  - Cytokine interactions with adrenal medullary chromaffin cells.
AB  - It is generally accepted that a bi-directional or reciprocal interaction occurs
      between the immune and neuroendocrine systems, and that this relationship is
      important for the appropriate physiological functioning of both systems.
      Similarly, an imbalance in this relationship may contribute to a number of
      pathologies, most notably those relating to stress. The aim of this article is to
      consider the interaction of cytokines with the adrenal medulla, a potentially
      important player in this relationship. The chromaffin cells of the adrenal
      medulla release catecholamines and a range of biologically active peptides in
      response to a wide variety of stress-related signals. A growing body of evidence
      indicates that this stress response is influenced by, and in turn has influence
      upon, immune signalling. This brief review will focus primarily on the best
      described adrenal medullary active cytokines, namely interferon-alpha,
      interleukin-6, interleukin-1alpha/beta and tumour necrosis factor-alpha. In each
      case, three key issues will be addressed: the physiologically relevant source of
      the cytokine; the intracellular signalling events arising from activation of its
      receptor and finally the cellular consequences of such activation in terms of
      modulation of gene expression and the secretory output of the chromaffin cells.

PMID- 21088884
TI  - The Rho guanine nucleotide exchange factors Intersectin 1L and beta-Pix control
      calcium-regulated exocytosis in neuroendocrine PC12 cells.
AB  - GTPases of the Rho family are molecular switches that play an important role in a
      wide range of membrane-trafficking processes including neurotransmission and
      hormone release. We have previously demonstrated that RhoA and Cdc42 regulate
      calcium-dependent exocytosis in chromaffin cells by controlling actin dynamics,
      whereas Rac1 regulates lipid organisation. These findings raised the question of
      the upstream mechanism activating these GTPases during exocytosis. The guanine
      nucleotide exchange factors (GEFs) that catalyse the exchange of GDP for GTP are
      crucial elements regulating Rho signalling. Using an RNA interference approach,
      we have recently demonstrated that the GEFs Intersectin-1L and beta-Pix, play
      essential roles in neuroendocrine exocytosis by controlling the activity of Cdc42
      and Rac1, respectively. This review summarizes these results and discusses the
      functional importance of Rho GEFs in the exocytotic machinery in neuroendocrine
      cells.

PMID- 21088885
TI  - Ca2+ dynamics in the secretory vesicles of neurosecretory PC12 and INS1 cells.
AB  - We have investigated the dynamics of the free [Ca(2+)] inside the secretory
      granules of neurosecretory PC12 and INS1 cells using a low-Ca(2+)-affinity
      aequorin chimera fused to synaptobrevin-2. The steady-state secretory granule
      [Ca(2+)] ([Ca(2+)](SG)] was around 20-40 MUM in both cell types, about half the
      values previously found in chromaffin cells. Inhibition of SERCA-type Ca(2+)
      pumps with thapsigargin largely blocked Ca(2+) uptake by the granules in Ca(2+)
      depleted permeabilized cells, and the same effect was obtained when the perfusion
      medium lacked ATP. Consistently, the SERCA-type Ca(2+) pump inhibitor
      benzohydroquinone induced a rapid release of Ca(2+) from the granules both in
      intact and permeabilized cells, suggesting that the continuous activity of SERCA
      type Ca(2+) pumps is essential to maintain the steady-state [Ca(2+)](SG). Both
      inositol 1,4,5-trisphosphate (InsP(3)) and caffeine produced a rapid Ca(2+)
      release from the granules, suggesting the presence of InsP(3) and ryanodine
      receptors in the granules. The response to high-K(+) depolarization was different
      in both cell types, a decrease in [Ca(2+)](SG) in PC12 cells and an increase in
      [Ca(2+)](SG) in INS1 cells. The difference may rely on the heterogeneous response
      of different vesicle populations in each cell type. Finally, increasing the
      glucose concentration triggered a decrease in [Ca(2+)](SG) in INS1 cells. In
      conclusion, our data show that the secretory granules of PC12 and INS1 cells take
      up Ca(2+) through SERCA-type Ca(2+) pumps and can release it through InsP(3) and
      ryanodine receptors, supporting the hypothesis that secretory granule Ca(2+) may
      be released during cell stimulation and contribute to secretion.

PMID- 21088887
TI  - Regulatory peptides from chromogranin A and secretogranin II.
AB  - This commentary is focusing on novel aspects on the secreted CgA- and SgII
      derived peptides, vasostatin-I (bovine and human CgA(1-76), VS-I), WE-14 (CgA(316
      329)), catestatin (bovine CgA(344-366), human CgA(352-372), Cts) and the SgII
      derived secretoneurin (SgII(180-204)) as significant regulators of inflammatory
      reactions.

PMID- 21088886
TI  - Estradiol inhibits depolarization-evoked exocytosis in PC12 cells via N-type
      voltage-gated calcium channels.
AB  - Fast neuromodulatory effects of 17-beta-estradiol (E2) on cytosolic calcium
      concentration ([Ca(2+)](i)) have been reported in many cell types, but little is
      known about its direct effects on vesicular neurotransmitter secretion
      (exocytosis). We examined the effects of E2 on depolarization-evoked [Ca(2+)](i)
      in PC12 cells using fluorescence measurements. Imaging of [Ca(2+)](i) with FURA-2
      revealed that depolarization-evoked calcium entry is inhibited after exposure to
      10 nM and 10 MUM E2. Calcium entry after exposure to 50 MUM E2 decreases
      slightly, but insignificantly. To relate E2-induced changes in [Ca(2+)](i) to
      functional effects, we measured exocytosis using amperometry. It was observed
      that E2 in some cells elicits exocytosis upon exposure. In addition, E2 inhibits
      depolarization-evoked exocytosis with a complex concentration dependence, with
      inhibition at both physiological and pharmacological concentrations. This rapid
      inhibition amounts to 45% at a near physiological level (10 nM E2), and 50% at a
      possible pharmacological concentration of 50 MUM. A small percentage (22%) of
      cells show exocytosis during E2 exposure ("Estrogen stimulated"), thus vesicle
      depletion could possibly account (at least partly) for the E2-induced inhibition
      of depolarization-evoked exocytosis. In cells that do not exhibit E2-stimulated
      release ("Estrogen quiet"), the E2-induced inhibition of exocytosis is abolished
      by a treatment that eliminates the contribution of N-type voltage-gated calcium
      channels (VGCCs) to exocytosis. Overall, the data suggest that E2 can act on N
      type VGCCs to affect secretion of neurotransmitters. This provides an additional
      mechanism for the modulation of neuronal communication and plasticity by
      steroids.

PMID- 21088888
TI  - Increased SIAH expression predicts ductal carcinoma in situ (DCIS) progression to
      invasive carcinoma.
AB  - Hyperactivated HER2/Neu/EGFR/RAS signaling is a major growth-promoting pathway
      known to drive cellular transformation and oncogenesis in breast cancers. HER2
      amplification is detected in ~20% of all human breast cancer and is quite
      prevalent (up to 49%) in ductal carcinoma in situ (DCIS). The E3 ubiquitin ligase
      SIAH is considered a key downstream "gatekeeper" required for proper
      HER2/EGFR/RAS signal transduction. Formalin-fixed, paraffin-embedded resection
      specimens from 65 patients with DCIS treated with wide excision only were stained
      with an anti-SIAH antibody, and the percentage of tumor and normal adjacent
      tissue cells positive for SIAH nuclear staining were recorded. Statistical
      analysis was performed comparing SIAH staining in tumor cells to disease
      recurrence, histologic type, necrosis, hormone receptor status, and Her2/neu
      status, as well as nuclear grade. Correlation of SIAH expression in tumor cells
      with SIAH expression in normal adjacent tissue and age was also examined.
      Expression levels of SIAH in tumor cells was significantly higher in specimens
      from patients with recurrence (median = 19%) as compared to patients without
      recurrence (7%) (P < 0.001). There was also significantly increased SIAH
      expression in tumors with more aggressive features including comedo morphology
      (13.5% in comedo vs. 7% in other histologic types, P = 0.014). No significant
      association was observed between SIAH expression and estrogen receptor,
      progesterone receptor, and Her2/neu status. There was a significant correlation
      between SIAH expression in tumors and normal adjacent tissue (Spearman
      correlation = 0.58, P < 0.001) as well as between SIAH expression in normal
      adjacent tissue and patient age (Spearman correlation = -0.59, P < 0.001). No
      significant correlation was identified between patient age and SIAH expression in
      tumors (Spearman correlation = -0.23, P = 0.067). In conclusion, SIAH may
      represent a useful prognostic biomarker that predicts DCIS progression to
      invasive breast cancer.

PMID- 21088889
TI  - Identification of microcystins contamination in surface water samples from the
      Three Gorges Reservoir, China.
AB  - Physicochemical and biological parameters related to water quality and
      microcystins (MCs) contamination in aquatic environment of the Three Gorges
      Reservoir were investigated in August 2004 and January 2005. A solid-phase
      extraction method and an HPLC equipped with photodiode array were used for MC-LR
      detection. A quantitative analysis showed the total MC-LR concentrations of water
      samples ranged from non-detectable to 0.57 MUg L-1 among the seven sampling
      sites. The highest MC-LR concentration was found at sampling site G (Wushan),
      which was followed by F (Kaixian), E (Wanzhou), D (Fuling), C (Cuntan), and A
      (Daxigou). The correlation analysis showed the MC-LR concentration was positively
      correlated with chlorophyll-a concentration. This result suggests that MC
      concentration in water can be indirectly estimated by analyzing the chlorophyll-a
      concentration. Overall, the results of this study suggest that more importance
      should be placed on monitoring of MC contamination and water quality in the Three
      Gorges Reservoir to ensure drinking water safety and reduce the potential
      exposure of people to these health hazards.

PMID- 21088890
TI  - Seroprevalence of brucellosis and its contribution to abortion in cattle, camel,
      and goat kept under pastoral management in Borana, Ethiopia.
AB  - The involvement of Brucella infection in causing abortion was investigated in a
      breeding female subpopulation of 283 cattle, 756 camels, and 757 goats. Serum
      samples were serially tested using the Rose Bengal test and complement fixation
      test. The study showed that anti-Brucella antibodies were prevalent in 10.6% (95%
      confidence interval (CI), 7.4, 14.9), 2.2% (95%CI, 1.4, 3.7), and 1.9% (95%CI,
      1.1, 3.2) of cattle, camel, and goats, respectively. Abortion was more commonly
      reported in camels (23.4%) than cattle (13.8%) and goats (12.4%). The results of
      this study suggested that Brucella infections contribute significantly to
      abortion in cattle (odds ratio (OR), = 4.7; 95%CI, 2.0, 10.8) and goats (OR =
      6.9; 95%CI, 2.2, 21.7) but not in camels. The number of young animals produced by
      breeding females seems to be apparently reduced in seropositive groups. Keeping
      more than two animal species at household level was found to be the risk factor
      for cattle (OR = 3.1; 95%CI, 1.2, 7.9) and camel (OR = 5.3; 95%CI, 1.2-23.5)
      seropositivity to Brucella infection when compared to those animals from
      households that keep only two animal species. This may suggest a possibility of
      cross species transmission of Brucella infection under such mixed herding. Wet
      season (OR = 4.8; 95%CI, 1.3, 18.1) was found to be associated with
      seropositivity in goats, linked to a coincidence of increased deliveries in
      flocks with possible excretion of Brucella organisms. The study results suggest
      that Brucella infection is the likely cause of abortion in cattle and goats while
      other causes largely outweigh brucellosis as a cause of abortion in camels in
      Borana, hence, contributing to reproductive loss.

PMID- 21088891
TI  - Growth performance of Nigerian local chickens in crosses involving an exotic
      broiler breeder.
AB  - Six-hundred-and-seven-day-old chicks were generated from Nigerian local chickens
      consisting of three genotypes (Normal-feathered; Frizzled-feathered; Naked neck)
      and an exotic broiler breeder (Anak Titan) to evaluate growth performance for
      possible meat-type chicken development. Growth parameters measured were body
      weight, breast girth and keel length on weekly basis for 20 weeks. Effects of
      sire, dam and chick genotypes were significant (P<0.001) on growth traits. At
      week 20, chickens sired by the Anak Titan weighed 1,614.82 g followed by Normal
      feathered local chickens with body weight of 1,211.32 g. Progenies of Anak Titan
      and Naked neck dams weighed 1,761.96 and 1,292.80 g at week 20, respectively.
      Among purebreds, Anak Titan weighed 35.05 g at day-old and had heaviest body
      weight of 2,360.29 g at 20 weeks compared to the three local strains. The average
      body weights for the crossbred, Normal-feathered * Anak Titan at day-old and week
      20 were 36.39 and 1,577.63 g, respectively. This was followed by Anak Titan *
      Naked neck with 33.32 g at day-old and 1,514.14 g at week 20. Sex had significant
      effect (P<0.05) at weeks 16 and 20 with the males having higher mean values than
      their female counterparts. This study revealed that crosses involving Anak Titan
      sire * Naked neck dam had highest growth performance, and there was no strain
      differences among the growth performance of purebred Nigerian local chickens.

PMID- 21088892
TI  - Ovicidal activity of seven Pochonia chlamydosporia fungal isolates on Ascaris
      suum eggs.
AB  - The ovicidal effect of the nematophagous fungus Pochonia chlamydosporia on eggs
      of Ascaris suum was tested under laboratory conditions. A. suum eggs were plated
      on 2% water-agar with seven fungal isolates (Isol. 5, Isol. 31, Isol. 1, VC1,
      Isol. 12, Isol. 22 and VC4) and control without fungus. After 5, 7, 10, 14, 15
      and 21 days of incubation, approximately 100 eggs were removed from the plates
      and classified according to the following parameters: type 1, biochemical and
      physiological effect without morphological damage to the eggshell, type 2, lytic
      effect with morphological alteration of the eggshell and embryo and type 3, lytic
      effect with morphological alteration of eggshell and embryo showing hyphal
      penetration and internal egg colonization. The isolates effectively destroyed A.
      suum eggs and all types of effects were observed during the experiment. There was
      no variation in ovicidal capacity (type 3 effect) among the isolates (p>0.05)
      throughout the experiment. After 21 days, isolate 5 showed the highest
      percentages of type 3 effect (58.33%). The results indicated that P.
      chlamydosporia (Isol. 5, Isol. 31, Isol. 1, VC1, Isol. 12, Isol. 22 and VC4) can
      destroy A. suum eggs and is, therefore, a potential biological control agent of
      nematodes.

PMID- 21088893
TI  - Prevalence of gastrointestinal nematodes in growing pigs in Kabale District in
      Uganda.
AB  - During the last 30 years, pig production in Uganda and neighbouring counties has
      increased markedly. Pigs are mainly kept as a source of income for small-scale
      farmers; however, the pig production is subject to several constraints, one of
      them being worm infections. A study was carried out in rural communities in
      Kabale District in the South Western part of Uganda in September and October 2007
      in order to estimate the prevalence of gastrointestinal nematode parasites in
      pigs based on coprological examination. Fifty-six households were randomly
      selected and visited. Housing system and deworming history were recorded. Faeces
      was sampled from rectum of one to five pigs (age, 3-12 months) per household. A
      total of 106 pigs were examined coprologically of which 91% excreted nematode
      eggs. The following prevalences of nematode eggs were recorded: strongyles (89%),
      Ascaris suum (40%), Trichuris suis (17%) and spiruroid eggs (48%). On household
      level, rearing pigs on slatted floors in pens significantly reduced the faecal
      egg excretion of strongyle eggs with almost 80% (p=0.010) and a significant
      interaction between floor type and anthelmintic treatment was found for
      spiruroids (p=0.037). Fifteen T. suis egg positive pigs were selected for post
      mortem examination of the gastrointestinal tract. The post-mortem examinations
      revealed that 93% pigs were infected with Oesophagostomum spp. (worm burden, min
      max 10-2,180), 73% with A. suum (1-36), 67% with T. suis (6-58), and 20% with
      Hyostrongylus rubidus (worms not quantified). In general, nematode infections
      were widespread and polyparasitism common in pigs in Uganda. However, worm
      burdens were moderate which may be related to recent deworming or to the practice
      of rearing pigs on slatted floors in wooden elevated pens.

PMID- 21088894
TI  - Anthelminthic activity of acetone extract and fractions of Vernonia amygdalina
      against Haemonchus contortus eggs and larvae.
AB  - The current control of parasitic nematodes in small ruminants relies on the use
      of chemical anthelminthics, but the development of resistance and the problem of
      drug residues require research into alternatives. Acetone extract and solvent
      solvent fractions of Vernonia amygdalina Del. (Compositae) were evaluated in
      vitro for potential anti-parasitic effects against the eggs and larvae of
      Haemonchus contortus. Significant effects were obtained with the extract and
      fractions but differences were observed depending on the parasitic stage. The
      acetone extract and fractions inhibited egg hatching and inhibited larval
      development and killed larvae of H. contortus in a concentration-dependent
      manner. Best-fit 50% lethal concentration (LC(50)) values were 957.0, 76.0,
      524.0, 309.0 and 224.0 MUg/ml for the acetone extract, and the butanol, hexane,
      chloroform and 35% water in methanol fractions, respectively, when tested against
      nematode eggs. Best-fit LC(50) values for the larval viability test were 508.2,
      485.5, 569.3, 348.9 and 196.6 MUg/ml for the acetone extract, and the butanol,
      hexane, chloroform and 35% water in methanol fractions, respectively. The butanol
      fraction was most active against nematode eggs while the 35% water in methanol
      fraction was the most active on nematode larvae, although differences in activity
      between fractions were not significant (p > 0.05). Overall, these in vitro
      results suggest that V. amygdalina, traditionally used by small farmers in
      Western Africa, does possess anti-parasitic properties.

PMID- 21088895
TI  - Effects of Streblus asper Lour foliage on digestibility, rumen fermentation, and
      nitrogen balance of growing goats.
AB  - Eighteen crossbred (Thai native x Anglo-Nubian) goats were chosen from a
      Suranaree University of Technology's farm on the basis of similar bodyweight
      (15.5 +/- 3.5 kg). The goats were randomly allocated to three treatments in
      randomized complete block design. Each goat was given urea-treated rice straw as
      roughage plus the respective treatment diets. The diets were iso-nitrogenous and
      iso-energetic containing cassava pulp, molasses, urea, and commercial mineral and
      vitamin mix. The experimental treatments were (1) soybean meal (SBM), (2) partial
      substitution of SBM with Streblus aspe Lour foliage, or (3) partial substitution
      of SBM with Leucaena (Leucaena leucocephala) foliage. Nutrient intakes, ruminal
      characteristics (pH, ammonia nitrogen, and volatile fatty acids), nitrogen
      balances, and plasma urea nitrogen were not significantly different among
      treatments. The present results indicate that protein foliages from locally grown
      shrubs and trees can substitute imported feedstuffs concentrate (e.g., SBM) as
      protein supplement for goat production.

PMID- 21088896
TI  - The role of imams in American Muslim health: perspectives of Muslim community
      leaders in Southeast Michigan.
AB  - American Muslims are a diverse and growing population, numbering nearly 200,000
      in Southeast Michigan. Little empirical work exists on the influence of Islam
      upon the healthcare behaviors of American Muslims, and there is to date limited
      research on the roles that imams, Muslim religious leaders, play in the health of
      this community. Utilizing a community-based participatory research (CBPR) model
      through collaboration with four key community organizations, we conducted semi
      structured interviews with 12 community leaders and explored their perceptions
      about the roles imams play in community health. Respondents identified four
      central roles for imams in healthcare: (1) encouraging healthy behaviors through
      scripture-based messages in sermons; (2) performing religious rituals around life
      events and illnesses; (3) advocating for Muslim patients and delivering cultural
      sensitivity training in hospitals; and (4) assisting in healthcare decisions for
      Muslims. Our analysis also suggests several challenges for imams stemming from
      medical uncertainty and ethical conflicts. Imams play key roles in framing
      concepts of health and disease and encouraging healthy lifestyles outside of the
      healthcare system, as well as advocating for Muslim patient needs and aiding in
      healthcare decisions within the hospital. Healthcare partnerships with these
      religious leaders and their institutions may be an important means to enhance the
      health of American Muslims.

PMID- 21088897
TI  - Philosophical implications of the systemic and patient-oriented management of
      chronic heart failure.
AB  - Chronic heart failure is a lifelong disease that involves a large variety of
      symptoms and, ultimately, the entire organism relatively early in the disease
      process. At least in part, this is in contrast to other chronic conditions such
      as diabetes, renal failure or cancer. Modern treatment of patients with chronic
      heart failure goes beyond the mere prescription of vasodilators or inotropes. The
      multitude of multi-organ involvements and associated symptoms unrelated to pure
      cardiac contractile failure, as well as the psychosocial burden for patients and
      their direct environment, calls for a re-engagement with the philosophical
      aspects of medical care. Such a process may well challenge the approach commonly
      taken by health care providers. We further suggest a broader and more holistic
      view of medical care--in this case in regard to heart failure--and one that is
      based on patients' and physicians' understanding of health and disease, autonomy,
      suffering, existential values and expectations that might positively affect
      treatment strategies and outcomes.

PMID- 21088899
TI  - IL-10 and TGF-beta2 are overexpressed in tumor spheres cultured from human
      gliomas.
AB  - Immune-associated cytokines including IL-10 and TGF-beta2 are thought to play a
      crucial role in immunosuppression mediated by gliomas. We have investigated the
      possibility that glioma stem cells are the major source of these cytokines. Tumor
      spheres, clonal non-adherent cell colonies derived from a single tumor stem cell,
      were cultured from surgical specimens of eight glioma patients, including two
      glioblastoma multiformes (grade IV), one anaplastic oligodendroglioma (grade III)
      and five anaplastic astrocytomas (grade III). Real-time RT-PCR and immunoassay
      were used to compare the relative expression levels of IL-10 and TGF-beta2 in
      stem-cell-derived tumor sphere cells (TSCs) and primary cultured glioma cells
      (PCGCs). TSCs were confirmed to express the brain tumor stem cell marker CD133,
      and on in vitro differentiation gave rise to cells expressing neuronal or glial
      markers. RT-PCR and immunoassay revealed that mRNA and protein levels of both IL
      10 and TGF-beta2 were significantly higher in TSCs than in PCGCs from the same
      tumor. Interestingly, the degree of overexpression in TSCs, but not in PCGS,
      appeared to correlate with the pathological grade of the glioma. These findings
      suggest that glioma stem cells are likely to be the major tumor source of
      immunosuppressive cytokines and thereby play a crucial role in determining glioma
      malignancy.

PMID- 21088898
TI  - Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type
      II and complex II-III deficiency in liver and muscle.
AB  - We describe a 22-year-old male who developed severe hypoglycemia and lethargy
      during an acute illness at 4 months of age and subsequently grew and developed
      normally. At age 4 years he developed recurrent vomiting with mild hyperammonemia
      and dehydration requiring frequent hospitalizations. Glutaric aciduria Type II
      was suspected based upon biochemical findings and managed with cornstarch,
      carnitine and riboflavin supplements. He did not experience metabolic crises
      between ages 4-12 years. He experienced recurrent vomiting, mild hyperammonemia,
      and generalized weakness associated with acute illnesses and growth spurts. At
      age 18 years, he developed exercise intolerance and proximal muscle weakness
      leading to the identification of multiple acyl-CoA dehydrogenase and complex
      II/III deficiencies in both skeletal muscle and liver. Subsequent molecular
      characterization of the ETFDH gene revealed novel heterozygous mutations,
      p.G274X:c.820 G > T (exon 7) and p.P534L: c.1601 C > T (exon 12), the latter
      within the iron sulfur-cluster and predicted to affect ubiquinone reductase
      activity of ETFDH and the docking of ETF to ETFDH. Our case supports the concept
      of a structural interaction between ETFDH and other enzyme partners, and suggests
      that the conformational change upon ETF binding to ETFDH may play a key role in
      linking ETFDH to II/III super-complex formation.

PMID- 21088900
TI  - In silico gene expression analysis in Codonopsis lanceolata root.
AB  - Expressed sequence tags (ESTs) provide valuable tools that can be used to predict
      the genes involved in primary and secondary metabolite synthesis. To the best of
      our knowledge, ESTs have not yet been developed for Codonopsis. lanceolata, and
      therefore, the EST referenced in this report is the first transcript for C.
      lanceolata. A cDNA library was constructed using the roots of C. lanceolata
      plants that were grown in a field. The selected 881 cDNA clones were sequenced
      and processed with an EST pipeline, resulting in 636 unique sequences, including
      517 singletons and 119 contig sequences. Using bioinformatics tools, 81% of the
      EST sequence was putatively annotated. Data for unique transcripts were mined
      from biological databases and functionally classified using gene ontology (GO),
      the Kyoto Encyclopedia of Genes and Genomes Orthology, KEGG pathway maps, and
      protein family. The GO-based analyses were examined in terms of biotic and
      abiotic stress response, transport, cellular component organization, biogenesis,
      and secondary metabolic processes. The KEGG-based analyses of most transcripts
      were sorted by carbohydrate metabolism, energy metabolism, and biosynthesis of
      secondary metabolites. Five randomly-selected putative genes were used for an
      expression study using various stresses such as salt, H(2)O(2), salicylic acid,
      and methyl jasmonic acid. Mined data were organized in "The Codonopsis EST
      Database" (www.bioherbs.khu.ac.kr/Codonopsis).

PMID- 21088901
TI  - Cloning and characterization of a wheat neutral ceramidase gene Ta-CDase.
AB  - Ceramidases are key enzymes in the regulation of the cellular levels of ceramide,
      sphingosine and sphingosine-1-phosphate. This study first reports on the
      molecular cloning, sequencing and expression profile of the gene encoding the
      wheat neutral ceramidase designated as Ta-CDase. A full length wheat Ta-CDase
      gene is obtained by rapid amplification of cDNA ends (RACE) based on the sequence
      of the WSRC36 fragment from an incompatible suppression subtractive hybridization
      (SSH) cDNA library of wheat leaves infected by Puccinia striiformis f. sp.
      tritici. The open reading frame (ORF) of 2,839 nucleotides encodes a polypeptide
      of 785 amino acids with a predicted isoelectric point (pI) of 6.398. The protein
      conserved domain search indicates that the polypeptide contains the signature of
      ceramidase, signal peptide sequence and transmembrane region. A phylogenetic
      analysis reveals that a high degree of relatedness exists among wheat Ta-CDase
      and ceramidases from other plant species at the amino acid level, while its
      relationship to that of animals and pathogens is more distant. The expression
      profile of the Ta-CDase shows a very strong expression of transcripts only at 48
      h post inoculation (hpi), while expression level is low at other time points.
      Southern blot analyses showed that Ta-CDase is a multi-copy gene and located on
      wheat chromosome 4D and 5A.

PMID- 21088902
TI  - Cloning and expression of stearoyl-CoA desaturase 1 (SCD-1) in the liver of the
      Sichuan white goose and landes goose responding to overfeeding.
AB  - The EST sequence of goose (Anser cygnoides) Stearoyl-CoA desaturase 1(SCD-1) was
      obtained from a subtractive cDNA library. To further investigate the role of SCD
      1 in lipid metabolism in geese, 5'-RACE and 3'-RACE were carried out in this
      study to obtain the complete cDNA sequence of goose SCD-1, which contained a 29
      bp 5' UTR, a 1074-bp open reading frame (ORF) encoding 357 amino acids, and a 125
      bp 3' UTR. The expression of SCD-1 was measured in several tissues, and the
      effects of overfeeding on the expression of SCD-1 were studied. The results of
      real time RT-PCR demonstrated that, compared to the brain, goose SCD-1 mRNA was
      more abundant in the liver. Overfeeding markedly increased the mRNA expression of
      SCD-1 in the liver of Sichuan White and Landes geese, and gene expression was
      markedly higher in the Sichuan White goose than in the landes goose. The mRNA
      abundance of SCD-1 in the liver had significant positive correlations with
      triacylglycerol (TG) content in liver lipids and in the levels of plasma insulin
      and very low-density lipoproteins (VLDL) levels in Sichuan white geese. However,
      the mRNA abundance of SCD-1 in the livers of Landes geese had only significant
      positive correlations with the TG content in liver lipids. In conclusion, SCD-1
      is not only critical for hepatic steatosis in geese but is also important for the
      difference in lipid deposition in the livers of the two breeds.

PMID- 21088903
TI  - Dietary intervention of cow ghee and soybean oil on expression of cell cycle and
      apoptosis related genes in normal and carcinogen treated rat mammary gland.
AB  - The present study investigated the effect of cow ghee (clarified butter fat)
      versus soybean oil on the expression of cyclins A and D1, and apoptosis
      regulating Bax, Bcl-2 and PKC-alpha genes in mammary gland of normal and 7,12
      dimethylbenz(a)anthracene (DMBA) treated rats. Two groups of 21 days old female
      rats were fed for 44 weeks diet containing cow ghee or soybean oil (10%). The
      animals were given DMBA (30 mg/kg body weight) through oral intubation after 5
      weeks feeding. Another two groups fed similarly but not given DMBA served as
      respective controls. In control groups, the expression of cyclin A was similar on
      both cow ghee and soybean oil, but that of cyclin D1 was more on soybean oil
      diet. However, in DMBA treated groups, the expression levels of cyclins A and D1
      were significantly greater on soybean oil than on cow ghee. The expression levels
      of Bax, Bcl-2 and PKC-alpha were similar in two control groups. However, in tumor
      tissue expression levels of Bcl-2 and PKC-alpha were significantly lower in cow
      ghee fed rats than in soybean oil fed ones, but Bax was similarly expressed in
      both DMBA treated groups. The pro-apoptotic ratio Bax/Bcl-2 increased and the
      anti-apoptotic ratio PKC-alpha(Bcl-2/Bax) decreased in cow ghee group compared to
      soybean oil group in DMBA treated rats. Hence, the decreased expressions of
      cyclins A and D1, Bcl-2 and PKC-alpha mediate the mechanism by which cow ghee
      protects from mammary carcinogenesis.

PMID- 21088904
TI  - Increase of cytosolic calcium induced by trichosanthin suppresses cAMP/PKC levels
      through the inhibition of adenylyl cyclase activity in HeLa cells.
AB  - Increase of cytosolic free calcium played a pivotal role in apoptotic cells
      induced by trichosanthin. However, little is known about the influence of
      cytosolic calcium increase on adenylyl cyclase activity and intracellular cAMP
      signaling pathway in HeLa cells. The present study showed that an influx of
      extracellular Ca2+ initiated by trichosanthin was required for the suppression of
      adenylyl cyclase activity and decrease of intracellular cAMP level. Furthermore,
      this inhibition was abolished by activation of PKC rather than PKA. Therefore,
      our results suggested that increase of cytosolic calcium induced by trichosanthin
      inhibits cAMP levels via suppression of adenylyl cyclase activity.

PMID- 21088905
TI  - Penicillium marneffei actin expression during phase transition, oxidative stress,
      and macrophage infection.
AB  - Penicillium marneffei is an opportunistic fungal pathogen that exhibits thermally
      regulated dimorphism. At 25 degrees C, this fungus grows vegetatively as mycelia,
      but at 37 degrees C or upon invasion of a host, a fission yeast form is
      established. Yet, despite increased numbers of molecular studies involving this
      fungus, the role of P. marneffei stress response-related proteins is not well
      characterized. Actin is one of the proteins that have been proposed to play a
      role not only in cell transition, but also in thermo-adaptation. Here, we report
      the isolation and characterization of the actin encoding gene, actA, from P.
      marneffei. Examination of the deduced amino acid sequence of the ActA protein
      revealed that it is closely related to Aspergillus nidulans and Aspergillus
      clavatus. Northern blot analysis of actin expression during the mycelium to yeast
      phase transition of P. marneffei showed that the actA transcripts were initially
      upregulated soon after shifting the incubation temperature from 25 degrees C to
      37 degrees C, but subsequently decreased slightly and did not change during
      further growth or under stress conditions. When cultures were started with
      conidia, upregulation of actA gene was found to correlate with germ tube
      production at either 25 degrees C or 37 degrees C. However, the relative
      expression level of actA transcripts again showed no significant differences in
      different cell types (conidia, mycelium, and yeast cells) or during macrophage
      infection. These results suggest that actin may play an important role in the
      early stages of cellular development, but not in environmental stress responses.

PMID- 21088906
TI  - Abundant variations of MC4R gene revealed by Phylogenies of Yak (Bos grunniens)
      and other mammals.
AB  - MC4R gene was proved to play important roles in body weight regulation in many
      mammals and exhibit higher homology among different species. The mutations MC4R
      significantly correlated to the restricted feeding weight, fat deposition and
      energy balance. In this work, ORF sequences of MC4R gene of Bos grunniens were
      cloned and phylogenetic relationships of yak and other mammals were analyzed on
      the basis of MC4R genes. Totally 290 variable sites were examined in 25 sequences
      from 22 different mammals, and 23 haplotypes were defined with a haplotype
      diversity of 0.9900. All the sequences were clustered into phylogenetic clades
      representing different orders or families. The individuals of Bos grunniens, Bos
      taurus and Ovis aries which belonged to the family of Bovidae were more divergent
      from the other orders or families and bovid animals may have branched out from
      the phylogenetic tree earlier than other mammals analyzed during 450 million
      years of vertebrate evolution. Amino acid sequences inferred from MC4R genes
      exhibited 54 variable sites, while high conservation of MC4R was observed within
      the same order or family. We concluded that coding region of MC4R gene displayed
      abundant variations among different mammal phylogenetic clades, whereas, the
      conservation of MC4R within order or family could be explained that MC4R gene may
      have been subjected to substantial constraints or strong purifying selection
      during several million years of mammal evolution.

PMID- 21088907
TI  - Inhibitory effect of hepatocyte growth factor on cardiomyocytes apoptosis is
      partly related to reduced calcium sensing receptor expression during a model of
      simulated ischemia/reperfusion.
AB  - Calcium-sensing receptors (CaSR) are G-protein coupled receptors which maintain
      systemic calcium haemeostasis, participate in hormone secretion, activation of
      iron channel, cell apoptosis, proliferation and differentiation. Previous studies
      have show CaSR induce apoptosis in isolated rat adult heart and in normal rat
      neonatal cardiomyocytes by G-protein-PLC-IP3 signaling transinduction. A few of
      studies had demonstrated that CaSR induce apoptosis in cultured neonatal rat
      cardiomyocytes during ischemia/reperfusion. Hepatocyte growth factor (HGF), as a
      mesenchymally derived heterodimeric glycoprotein, play vital role in mitogenesis,
      angiogenesis, cellular motility and growth and anti-apoptosis after
      postinfarction heart failure via activation of transmembrane tyrosine kinase cell
      surface receptor c-Met. However, little knowledge exists about whether anti
      apoptotic role of HGF in preventing cardiomyocytes injury induced by
      ischemia/reperfusion is associated with downregulation of CaSR expression. We
      incubated primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic
      solution for 2 h, then reincubated them in normal culture medium for 24 h to
      establish a model of simulated ischemia/reperfusion (I/R). Cardiomyocyte
      apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling. The expression of CaSR mRNA was detected by reverse
      transcriptase polymerase chain reaction (RT-PCR). In addition, we analyzed the
      expression of Caspase-3, Bcl-2 and Phosphoinositide 3-kinase (PI3K) by Western
      blotting. The simulated I/R enhances the expression of CaSR and cardiomyocyte
      apoptosis. GdCl3, a specific activator of CaSR, further increase the expression
      of CaSR and Cardiomyocyte apoptosis, along with upregulation of Caspase-3,
      downregulation of Bcl-2 and inhibiting PI3K phosphorylation. Combination of GdCl3
      with LY294002 (a selective PI3K inhibitor) increased Cardiomyocytes apoptosis but
      did not increased CaSR expression. Treatment of HGF decreased I/R- and GdCl3
      induced apoptosis by suppressing Caspase-3 and promoting Bcl-2 and PI3K
      phosphorylation expression in accordance with downregulation of CaSR expression.
      HGF exerts protective role in I/R-induced apoptosis at least in part by
      inhibiting CaSR expression along with promoting Bcl-2, suppressing Caspase-3
      expression and stimulating PI3K phosphorylation signaling pathway.

PMID- 21088908
TI  - Systematic analysis of gene expression level with tissue-specificity, function
      and protein subcellular localization in human transcriptome.
AB  - Recent studies have shown that, in mammals, the highly expressed genes have
      shorter gene length and their protein products have relatively lower evolutionary
      rates. However, the global relationship between genes' expression level and their
      features such as tissue-specificity, function and protein subcellular
      localization has not been investigated extensively, especially in mammalian. In
      order to solve it, we analysed 8,570 genes across 46 human tissues. Our results
      suggest that widely expressed genes have higher mean expression levels than
      tissue-specific ones and genes encoding zinc-finger proteins have low expression
      levels similar to that of DNA-binding proteins. In the analysis of protein
      subcellular localization, it is shown that nuclear and Golgi apparatus proteins
      have lower mean expression levels than those of mitochondria, endoplasmic
      reticulum and membrane proteins, while genes encoding cytoplasm and extracellular
      components display the highest expression levels. When comparing the gene
      expression levels and the number of expressed genes in different tissues, we
      found that some tissues have less active genes while single gene encodes
      relatively more transcripts. Taken together, gene expression levels are clearly
      correlated with their tissue-specificity, function and protein subcellular
      localization, and are highly conserved during evolution.

PMID- 21088909
TI  - PeaT1-induced systemic acquired resistance in tobacco follows salicylic acid
      dependent pathway.
AB  - Systemic acquired resistance (SAR) is an inducible defense mechanism which plays
      a central role in protecting plants from pathogen attack. A new elicitor, PeaT1
      from Alternaria tenuissima, was expressed in Escherichia coil and characterized
      with systemic acquired resistance to tobacco mosaic virus (TMV). PeaT1-treated
      plants exhibited enhanced systemic resistance with a significant reduction in
      number and size of TMV lesions on wild tobacco leaves as compared with control.
      The quantitative analysis of TMV CP gene expression with real-time quantitative
      PCR showed there was reduction in TMV virus concentration after PeaT1 treatment.
      Similarly, peroxidase (POD) activity and lignin increased significantly after
      PeaT1 treatment. The real-time quantitative PCR revealed that PeaT1 also induced
      the systemic accumulation of pathogenesis-related gene, PR-1a and PR-1b which are
      the markers of systemic acquired resistance (SAR), NPR1 gene for salicylic acid
      (SA) signal transduction pathway and PAL gene for SA synthesis. The accumulation
      of SA and the failure in development of similar level of resistance as in wild
      type tobacco plants in PeaT1 treated nahG transgenic tobacco plants indicated
      that PeaT1-induced resistance depended on SA accumulation. The present work
      suggested that the molecular mechanism of PeaT1 inducing disease resistance in
      tobacco was likely through the systemic acquired resistance pathway mediated by
      salicylic acid and the NPR1 gene.

PMID- 21088910
TI  - Studies on the interaction between benzophenone and bovine serum albumin by
      spectroscopic methods.
AB  - The interaction between benzophenone (BP) and bovine serum albumin (BSA) was
      investigated by the methods of fluorescence spectroscopy combined with UV-Vis
      absorption and circular dichroism (CD) measurements under simulative
      physiological conditions. The experiment results showed that the fluorescence
      quenching of BSA by BP was resulted from the formation of a BP-BSA complex and
      the corresponding association constants (Ka) between BP and BSA at four different
      temperatures had been determined using the modified Stern-Volmer equation. The
      enthalpy change (DeltaH) and entropy change (DeltaS) were calculated to be -43.73
      kJ mol(-1) and -53.05 J mol(-1) K(-1), respectively, which suggested that
      hydrogen bond and van der Waals force played major roles in stabilizing the BP
      BSA complex. Site marker competitive experiments indicated that the binding of BP
      to BSA primarily took place in site I (sub-domain IIA). The conformational
      investigation showed that the presence of BP decreased the alpha-helical content
      of BSA and induced the slight unfolding of the polypeptides of protein, which
      confirmed some micro-environmental and conformational changes of BSA molecules.

PMID- 21088911
TI  - Relationships between COL2A1 gene polymorphisms and knee osteoarthritis in Han
      Chinese women.
AB  - To investigate the relationships between two COL2A1 single nucleotide
      polymorphisms (SNPs; T2088C and G4006A) and osteoarthritis (OA) in Han Chinese
      women. One hundred and twenty OA women and 120 control women were recruited.
      Genomic DNA was extracted from the whole blood. The COL2A1 polymorphisms T2088C
      and G4006A were analyzed by TaqMan assay. The levels of plasma N-propetide of
      type IIA collagen (PIIANP) and urinary C-telopeptide of type IIA collagen (CTX
      II) were determined by ELISA. The level of plasma PIIANP significantly decreased
      in the OA group, compared with that in the control group (P<0.05), with 15.6+/
      4.2 ng/ml (Mean+/-SD) in the OA group and 30.2+/-7.8 ng/ml in the control group.
      The level of urinary CTX-II significantly increased in the OA group, compared
      with that in the control group (P<0.05), with 201.4+/-10.2 ng/ml in the control
      group and 250.8+/-15.6 ng/ml in the OA group. There was no difference in the
      T2088C genotypes between the OA and control groups. The G4006A AA homozygous
      genotype significantly increased in the OA patients, when compared with that in
      the control women (P<0.05, chi2), with 24.2% (29/120) in the OA group and 10.0%
      (12/120) in the control group; The A allele accounted for 49.2% (118/240) in the
      OA group and 35.8% (86/240) in the control group. Among the G4006A genotypes, the
      plasma PIIANP level of the AA genotype (16.4+/-6.6 ng/ml) was significantly lower
      than those of the GG genotype (28.6+/-4.2 ng/ml) and GA genotype (21.5+/-8.0
      ng/ml) while the urinary CTX-II level of the AA genotype (255.2+/-18.4 ng/ml)
      significantly increased, compared with those of the GG genotype (218.4+/-13.2
      ng/ml) and GA genotype (221.2+/-15.6 ng/ml). The haplotype analysis shows that T
      G was a protective factor for OA and that T-A was a risk factor. The AA genotype,
      A allele and T-A may increase the risk of OA in the Han Chinese women while T-G
      may protect these women from OA.

PMID- 21088912
TI  - Comparison of 7-day and repeated 24-h recall of type 2 diabetes.
AB  - PURPOSE: Patient reporting of type 2 diabetes symptoms in a questionnaire with a
      7-day recall period was expected to be different from symptom reports using a 7
      day diary with repeated 24-h recall based on cognitive theory of memory processes
      and prior literature. This study compared these two types of recall in patients
      diagnosed with type 2 diabetes (T2D). METHODS: One hundred and forty adults with
      T2D completed a daily diary for 7 days containing 9 T2D-related symptom and
      impact items. On day 7, patients completed the same items with a 7-day recall
      period. We examined the concordance of 7-day recall with summary descriptors of
      the daily reports and compared the scores and the discriminant ability of 7-day
      recall and mean of daily reports. RESULTS: Seven-day recall was most concordant
      with the mean of daily reports. The average difference in scores was small (range
      0.22-0.77 on 11-point scale) and less than 0.5 standard deviations. For some
      items, the difference was positively associated with the variation in daily
      reports. The discriminant ability was comparable. CONCLUSIONS: In this study
      population, a questionnaire with 7-day recall provided information consistent
      with a daily diary measure of the average week-long experience of T2D symptoms
      and impacts.

PMID- 21088913
TI  - Validation of the psychometric properties of the health-promoting lifestyle
      profile in a sample of Taiwanese women.
AB  - PURPOSE: To examine the preliminary psychometric properties of the Chinese health
      promoting lifestyle profile II (HPLP II) among Taiwanese women. METHODS: We
      conducted a secondary analysis of cross-sectional data from 137 middle-aged women
      in southern Taiwan. HPLP II reliability was estimated with Cronbach's alpha
      coefficient, and concurrent validity was estimated with Pearson's correlation
      between the HPLP II, the World Health Organization's abbreviated Quality of Life
      assessment (WHOQOL-BREF), perceived health, and demographic variables.
      Confirmatory factor analysis (CFA) evaluated construct validity. RESULTS: Initial
      CFA using a six-factor measurement model aligned with the original HPLP II,
      excepting the factor loading of one subsequently excluded item. CFA of the
      revised 51-item HPLP II yielded a good estimate of fit. Correlations between the
      revised instrument and the six subscales were acceptable >0.7. The Cronbach's
      alpha coefficient surpassed 0.7 for the revised instrument and six subscales
      ranged from 0.71 to 0.91. The relationships between the 51-item instrument,
      perceived health, WHOQOL-BREF domain scores, and demographic variables were also
      significantly positive. CONCLUSIONS: The revised HPLP II scale is appropriate to
      measure the health-promoting lifestyles of Taiwanese women.

PMID- 21088914
TI  - To supplement or not to supplement: a cost-utility analysis of calcium and
      vitamin D repletion in patients after thyroidectomy.
AB  - BACKGROUND: Postoperative hypocalcemia is the most common complication after
      thyroidectomy; prevention and treatment remain areas of ongoing debate. The
      purpose of this study was to determine the incremental cost utility of routine
      versus selective calcium and vitamin D supplementation after total or completion
      thyroidectomy. METHODS: A cost-utility analysis using a Markov decision model was
      performed for a hypothetical cohort of adult patients after thyroidectomy.
      Routine or selective supplementation of oral calcium carbonate, vitamin D
      (calcitriol), and intravenous calcium gluconate, when required, was used.
      Selective supplementation was determined by serum intact parathyroid hormone
      levels. The incremental cost utility, measured in U.S. dollars per quality
      adjusted life-year (QALY), was calculated. RESULTS: In the base-case analysis,
      the cost of routine supplementation was $102 versus $164 for selective
      supplementation. Patients in the routine arm gained 0.002 QALYs compared to
      patients in the selective arm (0.95936 QALYs vs. 0.95725 QALYs). At the
      population level, this translates into a savings of $29,365/QALY (95% confidence
      interval, -$66,650 to -$1,772) for routine supplementation. Sensitivity analyses
      demonstrated that the model was most sensitive to the utility of the hypocalcemic
      state, postoperative rates of hypocalcemia, and cost of serum parathyroid hormone
      testing. CONCLUSIONS: Routine oral calcium and calcitriol supplementation in
      patients after thyroidectomy seems to be less expensive and results in higher
      patient utility than selective supplementation. Surgeons who have very low rates
      of hypocalcemia in their patients may benefit less from routine supplementation.

PMID- 21088915
TI  - Robotic left pancreatectomy for pancreatic solid pseudopapillary tumor.
AB  - BACKGROUND: Solid pseudopapillary pancreatic tumors of pancreas are a rare
      entity, seen most often in females in their second or third decades. Although
      previously believed to be benign, this tumor is currently considered a low-grade
      malignant epithelial neoplasm with low metastatic rate and high overall
      survival.1,2 Its resection could be performed by robotic technique with respect
      to oncological principles to avoid tumor cell dissemination.3 METHODS: In this
      multimedia article, we present a 28-year-old female with a history of
      hyperthyroidism who underwent a computed tomography (CT) scan because of a
      persistent high C-reactive protein level following caesarean section. This CT
      scan revealed a 7-cm cystic lesion of the pancreatic tail. The serum tumor marker
      CA 19-9 was normal. Further investigation with an magnetic resonance imaging
      (MRI) scan showed that the lesion was macrocystic with internal septas compatible
      with a solid pseudopapillary neoplasm.4 The patient was treated with robotic
      distal splenopanceatectomy (video). RESULTS: The operative time was 5 h with an
      estimated blood loss of 250 mL. No blood transfusion was necessary. The
      postoperative period was uneventful, and she was discharged on postoperative day
      8. The histological finding revealed a solid pseudopapillary tumor of the
      pancreas pT2pN0 (0/14 lymph nodes removed). There was no evidence of clinical,
      biological, and radiological pancreatic fistula, and a control CT scan on
      postoperative day 8 did not show any abdominal fluid collection. The patient's 1
      month follow-up was normal. DISCUSSION: The robotic distal splenopancreatectomy
      is a procedure that offers some technical and oncological advantages over the
      already described minimally invasive techniques for distal pancreatic tumors.5,6
      These advantages are mainly due to the stability of the operative field, to the
      3D and magnified vision, and to the articulated robotic arms.7-9 The 3D
      representation and the stability of the operative field facilitate the
      performance of operative steps, as the creation of the retropancreatic tunnel and
      vascular identification. Moreover, the robotic articulated arms permit a superior
      handling of vascular structures, allowing a fine dissection that is extremely
      useful during lymphadenectomy. Articulated instruments easily achieve the correct
      rotation axis, thus minimizing peri-pancreatic tissue retraction and manipulation
      of the pancreatic gland. This smooth and no-touch technique in theory minimizes
      the risk of pancreatic capsule rupture as well as tumor cell dissemination,
      respecting oncological surgical standards. However, robotic surgery needs an
      adequate learning curve, especially concerning the installation and the lack of
      force feedback. CONCLUSION: The robotic distal pancreatectomy is a possible
      minimally invasive technique for patients with solid pseudopapillary pancreatic
      tumors. It presents some advantages over the laparoscopic approach. Nevertheless
      its oncological indications are yet to be defined.10.

PMID- 21088916
TI  - Congenital central hypoventilation syndrome due to PHOX2B mutation in a Saudi
      child: a case report.

PMID- 21088917
TI  - The effect of angulation in abdominal aortic aneurysms: fluid-structure
      interaction simulations of idealized geometries.
AB  - Abdominal aortic aneurysm (AAA) represents a degenerative disease process of the
      abdominal aorta that results in dilation and permanent remodeling of the arterial
      wall. A fluid structure interaction (FSI) parametric study was conducted to
      evaluate the progression of aneurysmal disease and its possible implications on
      risk of rupture. Two parametric studies were conducted using (i) the iliac
      bifurcation angle and (ii) the AAA neck angulation. Idealized streamlined AAA
      geometries were employed. The simulations were carried out using both isotropic
      and anisotropic wall material models. The parameters were based on CT scans
      measurements obtained from a population of patients. The results indicate that
      the peak wall stresses increased with increasing iliac and neck inlet angles.
      Wall shear stress (WSS) and fluid pressure were analyzed and correlated with the
      wall stresses for both sets of studies. An adaptation response of a temporary
      reduction of the peak wall stresses seem to correlate to a certain extent with
      increasing iliac angles. For the neck angulation studies it appears that a
      breakdown from symmetric vortices at the AAA inlet into a single larger vortex
      significantly increases the wall stress. Our parametric FSI study demonstrates
      the adaptation response during aneurysmal disease progression and its possible
      effects on the AAA risk of rupture. This dependence on geometric parameters of
      the AAA can be used as an additional diagnostic tool to help clinicians reach
      informed decisions in establishing whether a risky surgical intervention is
      warranted.

PMID- 21088918
TI  - Baroreflex analysis in diabetes mellitus: linear and nonlinear approaches.
AB  - The aim of our study was to employ novel nonlinear synchronization approaches as
      a tool to detect baroreflex impairment in young patients with subclinical
      autonomic dysfunction in Type 1 diabetes mellitus (DM) and compare them to
      standard linear baroreflex sensitivity (BRS) methods. We recorded beat-to-beat
      pulse interval (PI) and systolic blood pressure (SBP) in 14 DM patients and 14
      matched healthy controls. We computed the information domain synchronization
      index (IDSI), cross-multiscale entropy, joint symbolic dynamics, information
      based similarity index (IBSI) in addition to time domain and spectral measures of
      BRS. This multi parametric analysis showed that baroreflex gain is well
      preserved, but the time delay within the baroreflex loop is significantly
      increased in patients with DM. Further, the level of similarity between blood
      pressure and heart rate fluctuations was significantly reduced in DM. In
      conclusion, baroreflex function in young DM patients is changed. The
      quantification of nonlinear similarity and baroreflex delay in addition to
      baroreflex gain may provide an improved diagnostic tool for detection of
      subclinical autonomic dysfunction in DM.

PMID- 21088919
TI  - Oxidative stability of marine phospholipids in the liposomal form and their
      applications.
AB  - Marine phospholipids (MPL) have attracted a great deal of attention recently as
      they are considered to have a better bioavailability, a better resistance towards
      oxidation and a higher content of eicosapentaenoic (EPA) and docosahexaenoic
      acids (DHA) than oily triglycerides (fish oil) from the same source. Due to their
      tight intermolecular packing conformation at the sn-2 position and their
      synergism with alpha-tocopherol present in MPL extracts, they can form stable
      liposomes which are attractive ingredients for food or feed applications.
      However, MPL are still susceptible to oxidation as they contain large amounts
      polyunsaturated fatty acids and application of MPL in food and aquaculture
      industries is therefore a great challenge for researchers. Hence, knowledge on
      the oxidative stability of MPL and the behavior of MPL in food and feed systems
      is an important issue. For this reason, this review was undertaken to provide the
      industry and academia with an overview of (1) the stability of MPL in different
      forms and their potential as liposomal material, and (2) the current applications
      and future prospects of MPL in both food and aquaculture industries with special
      emphasis on MPL in the liposomal form.

PMID- 21088921
TI  - Going public: good scientific conduct.
AB  - The paper addresses issues of scientific conduct regarding relations between
      science and the media, relations between scientists and journalists, and
      attitudes towards the public at large. In the large and increasing body of
      literature on scientific conduct and misconduct, these issues seem underexposed
      as ethical challenges. Consequently, individual scientists here tend to be left
      alone with problems and dilemmas, with no guidance for good conduct. Ideas are
      presented about how to make up for this omission. Using a practical, ethical
      approach, the paper attempts to identify ways scientists might deal with ethical
      public relations issues, guided by a norm or maxim of openness. Drawing on and
      rethinking the CUDOS codification of the scientific ethos, as it was worked out
      by Robert K. Merton in 1942, we propose that this, which is echoed in current
      codifications of norms for good scientific conduct, contains a tacit maxim of
      openness which may naturally be extended to cover the public relations of
      science. Discussing openness as access, accountability, transparency and
      receptiveness, the argumentation concentrates on the possible prevention of
      misconduct with respect to, on the one hand, sins of omission-withholding
      important information from the public-and, on the other hand, abuses of the
      authority of science in order to gain publicity. Statements from interviews with
      scientists are used to illustrate how scientists might view the relevance of the
      issues raised.

PMID- 21088920
TI  - Presence and correlates of racial disparities in adherence to colorectal cancer
      screening guidelines.
AB  - OBJECTIVES: We examined the presence and correlates of Black/White racial
      disparities in adherence to guidelines for colorectal cancer screening (CRCS).
      METHODS: The sample included 328 Black and 1827 White patients age 50-75 from 24
      VA medical facilities who responded to a mailed survey with phone follow-up
      (response rate: 73% for Blacks and 89% for Whites). CRCS adherence and race were
      obtained through surveys and supplemented with administrative data. Logistic
      regressions estimated the contribution of demographic, health, cognitive, and
      environmental factors to racial disparities in adherence to CRCS guidelines.
      RESULTS: In unadjusted analyses, Blacks had slightly lower rates of adherence to
      CRCS guidelines than Whites (72% versus 77%, p<0.05). This racial disparity in
      CRCS adherence was explained by race differences in demographic, health, and
      environmental factors but not by cognitive factors. Tests for interactions
      revealed that the association of race with adherence varied significantly across
      levels of income, education, and marital status. In particular, among those who
      were married with higher levels of education, CRCS adherence was significantly
      higher for Whites; whereas among those who were unmarried, with low levels of
      education, adherence was significantly higher for Blacks. CONCLUSION: We found
      that disparities in CRCS are greatly attenuated in the VA system and both Whites
      and Blacks have substantially higher rates of CRCS than the national average.
      These results point to the success of the VA at implementing CRCS system-wide.
      Our findings also suggest additional initiatives may be needed for unmarried low
      income white men and higher income black men.

PMID- 21088922
TI  - Regional variations in testicular cancer rates in Ireland.
AB  - BACKGROUND: Traditionally, the incidence of testicular cancer (TCa) has shown a
      remarkable geographical variation. AIMS: To examine whether the rates of TCa
      varied within Ireland itself and to find possible explanations for any
      observations made. METHODS: We observed the incidence of TCa in counties in
      Ireland between January 1994 and December 2007. The rate of cryptorchidism over
      the same time was calculated. Incidence of TCa by socio-economic status was
      reviewed. The role of environmental pollutants was explored. We analysed teenage
      obesity data as a risk factor for the development of TCa in adulthood. RESULTS:
      Cork had a significantly higher rate of TCa than any other county in Ireland.
      Cork also had high rates of cryptorchidism, but interestingly not the highest
      nationwide. In Cork County specifically, least deprived areas had significantly
      higher rates of TCa. Organic pollutants previously linked to the development of
      TCa have been identified in large industries located only in Cork. Teenage
      obesity rates in Cork were not higher than elsewhere. CONCLUSIONS: There is a
      higher incidence rate of TCa in Cork than any other county. High rates of
      cryptorchidism alone cannot explain this. There appears to be a link with higher
      socio-economic status and possibly industrial pollutants. The association between
      sedentary lifestyle and the development of TCa is unproven.

PMID- 21088923
TI  - Axis I psychopathology in bariatric surgery candidates with and without binge
      eating disorder: results of structured clinical interviews.
AB  - BACKGROUND: Prior studies have reached contradictory conclusions concerning
      whether binge eating disorder (BED) is associated with greater psychopathology in
      extremely obese patients who seek bariatric surgery. This study used the
      Structured Clinical Interview for DSM-IV Diagnoses (SCID) to compare rates of
      axis I psychopathology in surgery candidates who were determined to have BED or
      to be currently free of eating disorders. The relationship of BED to other
      psychosocial functioning and weight loss goals also was examined. METHODS: One
      hundred ninety five bariatric surgery patients completed the Weight and Lifestyle
      Inventory and the Beck Depression Inventory-II (BDI-II) and were later
      administered the Eating Disorder Examination. Of these 195, 44 who were diagnosed
      with BED, and 61 who were currently free of eating pathology, completed a
      telephone-administered SCID. RESULTS: Significantly more BED than non-BED
      participants had a current mood disorder (27.3% vs. 4.9%, p = 0.002) as well as a
      lifetime history of this condition (52.3% vs. 23.0%, p = 0.003). More BED than
      non-BED participants also had a current anxiety disorder (27.3% vs. 8.2%, p =
      0.014) and lifetime anxiety disorder (36.4% vs. 16.4%, p = 0.019). BED also was
      associated with greater symptoms of depression, as measured by the BDI-II, as
      well as with lower self-esteem. BED and non-BED groups, however, did not differ
      in their desired weight loss goals following surgery. CONCLUSIONS: The present
      findings indicate that the presence of BED, in patients who seek bariatric
      surgery, is associated with an increased prevalence of axis I psychopathology,
      beyond the already elevated rate observed with severe (i.e., class III) obesity.

PMID- 21088924
TI  - Time-resolved MRI after ingestion of liquids reveals motility changes after
      laparoscopic sleeve gastrectomy--preliminary results.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is generally considered a
      restrictive procedure. However, studies with nuclear medicine techniques have
      demonstrated that gastric motility changes occur following LSG. These motility
      changes could represent complementary mechanisms of weight loss. Therefore, we
      analyzed the stomach motility before and after LSG by means of dynamic MRI.
      METHODS: In this prospective pilot study, five female patients with a mean BMI of
      51.6 kg/m(2) underwent MRI 1 day before LSG and 6 days and 6 months after LSG.
      Dynamic steady-state free precession sequences were used to analyze the gastric
      motility after ingestion of 500 ml water with a temporal resolution of 0.86 s.
      Axial image stacks were also repeatedly acquired to determine the intragastric
      fluid volume over time. RESULTS: Mean excess body mass index loss was 60.6% after
      6 months. Dynamic analysis showed that antral propulsive peristalsis was
      preserved immediately after surgery and during follow-up, but fold speed
      increased significantly from 2.7 mm/s before LSG to 4.4 mm/s after 6 months. The
      sleeve itself remained without recognizable peristalsis in three patients and
      showed only uncoordinated or passive motion in two patients. Consequently, the
      fluid transport through the sleeve was markedly delayed, whereas the antrum
      showed accelerated propulsion with the emptying half-time decreasing from 16.5
      min preoperatively to 7.9 min 6 months after surgery. CONCLUSIONS: Owing to the
      LSG procedure, the stomach is functionally divided into a sleeve without
      propulsive peristalsis and an accelerated antrum. Accelerated emptying seems to
      be caused by faster peristaltic folds.

PMID- 21088925
TI  - The gastric sleeve: losing weight as fast as micronutrients?
AB  - BACKGROUND: Recently, the laparoscopic sleeve gastrectomy (LSG) has become
      popular as a single-stage procedure for the treatment of morbid obesity and its
      co-morbidities. However, the incidence of micronutrient deficiencies after LSG
      have hardly been researched. METHODS: From January 2005 to October 2008, 60
      patients underwent LSG. All patients were instructed to take daily vitamin
      supplements. Patients were tested for micronutrient deficiencies 6 and 12 months
      after surgery. RESULTS: Anemia was diagnosed in 14 (26%) patients. Iron, folic
      acid, and vitamin B12 deficiency was found in 23 (43%), eight (15%), and five
      (9%) patients, respectively. Vitamin D and albumin deficiency was diagnosed in 21
      (39%) and eight (15%) patients. Hypervitaminosis A, B1, and B6 were diagnosed in
      26 (48%), 17 (31%), and 13 (30%) patients, respectively. CONCLUSIONS: Due to
      inadequate intake and uptake of micronutrients, patients who underwent LSG are at
      serious risk for developing micronutrient deficiencies. Moreover, some vitamins
      seem to increase to chronic elevated levels with possible complications in the
      long-term. Multivitamins and calcium tablets should be regarded only as a minimum
      and supplements especially for iron, vitamin B12, vitamin D, and calcium should
      be added to this regimen based on regular blood testing.

PMID- 21088926
TI  - Integrated bioabsorbable tissue reinforcement in laparoscopic sleeve gastrectomy.
AB  - Division of the stomach in laparoscopic sleeve gastrectomy may be performed using
      bare stapler cartridges or cartridges fitted with tissue reinforcement strips,
      with or without oversewing. Many tissue reinforcement strips are after-market add
      on products that must be fitted onto a stapler during surgery. A retrospective
      review was conducted of 85 consecutive patients undergoing laparoscopic sleeve
      gastrectomy using a novel integrated bioabsorbable polymer buttress pre-mounted
      on a single-use loading unit stapler. Mean preoperative body mass index (BMI) was
      41.7 +/- 5.2 kg/m(2). Morbidity and short-term outcomes were documented. Mean
      follow-up was 8.1 +/- 3.6 months (range, 1.0-16.2 months). There were no
      mortalities or staple line leaks noted in this series with short-term follow up.
      The major complication rate (grade III and above) was 7.1% and included:
      reoperation for staple line bleeding (2.4%, n = 2), gastric sleeve stenosis
      requiring balloon dilation (2.4%, n = 2), choledocholithiasis 2 weeks after
      surgery (1.2%, n = 1), and reoperation without abnormality for suspected
      perioperative obstruction (1.2%, n = 1). Mean percent excess BMI loss at 3 (44.6
      +/- 11.3), 6 (57.9 +/- 17.2), and 12 months (72.4 +/- 27.5) was comparable to
      other published series. The use of an integrated absorbable synthetic polymer for
      stapled tissue reinforcement in laparoscopic sleeve gastrectomy appears to be
      feasible and safe, and yields results consistent with other published techniques.

PMID- 21088927
TI  - The effects of laparoscopic adjustable gastric banding on idiopathic intracranial
      hypertension.
AB  - The purpose of this study was to determine whether laparoscopic adjustable
      gastric banding has a role in the treatment of idiopathic intracranial
      hypertension. This pilot study was undertaken in a single, tertiary referral
      centre. Data on all patients with idiopathic intracranial hypertension that have
      undergone laparoscopic adjustable gastric banding in our unit were collected from
      our prospectively maintained bariatric database. Additional information was
      obtained via telephone questionnaires and review of medical records. Four female
      patient with a mean age of 32 years (range 29-39 years) and mean pre-operative
      body mass index of 46.1 kg/m(2) (range 38.2-54.0 kg/m(2)) underwent laparoscopic
      adjustable gastric banding between June 2006 and July 2009. At a mean follow-up
      of 19.8 months all four patients reported either total resolution of headache or
      significant improvement in headache, with a mean improvement in pain score of
      76.3/100 (range 55-95) on a analogue pain score. Mean excess weight loss at
      follow-up was 64.1% (range 50.1-88.2%). There were no complications or mortality
      in this cohort. This study suggests that laparoscopic adjustable gastric banding
      represents an effective and safe treatment for idiopathic intracranial
      hypertension associated with morbid obesity. We have shown good results both in
      terms of symptom resolution and weight loss, whilst avoiding alimentary tract
      diversion procedures in these young female patients. A randomized, controlled
      trial can be justified on the basis of this initial pilot study.

PMID- 21088928
TI  - Prophylactic inferior vena cava filters in high-risk bariatric surgery.
AB  - BACKGROUND: Bariatric patients are at significant risk for venous thromboembolism
      (VTE) and a subset may benefit from retrievable inferior vena cava filters
      (rIVCFs). Optimal VTE prophylaxis and a consensus on factors which make bariatric
      patients high risk have not been established. This study describes our experience
      with the use of rIVCFs in combination with chemoprophylaxis for high-risk
      bariatric surgery patients. METHODS: A retrospective review was performed of high
      risk patients bariatric surgery patients. Patients with a hypercoaguable
      condition, prior history of VTE, body mass index (BMI) > 55 kg/m(2), and severe
      immobility were considered high risk. Patients underwent rIVCF placement and
      standard chemoprophylaxis. A venogram was performed at retrieval. RESULTS: Forty
      four patients, age of 48 +/- 12 years and BMI of 58.4 +/- 9.4 kg/m(2) underwent
      gastric bypass with rIVCF placement. Follow-up was 204 days. One patient had a
      preoperative deep venous thrombosis (DVT). All patients received chemoprophylaxis
      and rIVCF placement. Indications for rIVCF were BMI (68%), prior VTE (30%), and
      immobility (2%). The operation was performed laparoscopically in all patients,
      and the mean operative time was 106.1 +/- 21.6 min and length of stay was 3.1 +/-
      1.2 days. Postoperative venous duplex revealed two DVTs (5%). Retrieval was
      successful in 28 patients. No significant thrombus was found on venogram. Two
      minor complications of filter placement occurred. One mortality occurred due to
      MI, and no pulmonary emboli were clinically evident. CONCLUSIONS: rIVCFs in our
      cohort of high-risk bariatric surgery patients was associated with an acceptably
      low incidence of DVT (5%) and no clinically evident PE. Despite safe removal
      after long dwell times, previous data suggest that rIVCFs are associated with a
      higher incidence of VTE. Thus, filters, if placed, should be removed once the
      risk of VTE has passed. Larger multicenter studies are needed to truly identify
      long-term safety and efficacy of rIVCFs.

PMID- 21088930
TI  - The liver tissue bank and clinical database in China.
AB  - To develop a standardized and well-rounded material available for hepatology
      research, the National Liver Tissue Bank (NLTB) Project began in 2008 in China to
      make well-characterized and optimally preserved liver tumor tissue and clinical
      database. From Dec 2008 to Jun 2010, over 3000 individuals have been enrolled as
      liver tumor donors to the NLTB, including 2317 cases of newly diagnosed
      hepatocellular carcinoma (HCC) and about 1000 cases of diagnosed benign or
      malignant liver tumors. The clinical database and sample store can be managed
      easily and correctly with the data management platform used. We believe that the
      high-quality samples with detailed information database will become the
      cornerstone of hepatology research especially in studies exploring the diagnosis
      and new treatments for HCC and other liver diseases.

PMID- 21088929
TI  - Effect of heparin, fucoidan and other polysaccharides on adhesion of
      enterohepatic helicobacter species to murine macrophages.
AB  - Helicobacter species have been isolated and cultured from both the gastric and
      enterohepatic niches of the gastrointestinal tract and are associated with a wide
      spectrum of diseases. Some members of the enterohepatic Helicobacter species
      (EHS), which include Helicobacter bilis, Helicobacter hepaticus and Helicobacter
      pullorum, are associated with chronic inflammatory and proliferative bowel
      inflammation, hepatitis and in experimental murine studies with hepatic cancer.
      The present study aimed to explore if polysulphated polysaccharides can prevent
      adhesion of EHS to the murine macrophage cell line J774A.1. A competitive binding
      assay showed that heparin and heparan sulphate at a concentration of 1.25 mg/ml
      reduced binding of H. hepaticus and H. pullorum to the host cells, but not H.
      bilis. Of the tested Helicobacter spp, the highest inhibition by heparin was
      demonstrated for H. pullorum (P < 0.01), the most hydrophilic strain. Partially
      or completely de-sulphated heparin derivatives lost the ability to inhibit
      adherence of EHS, indicating the importance of sulphated groups of heparin. The
      most efficient inhibitor of EHS binding to macrophages was fucoidan, which
      reduced bacterial adhesion of the three enterohepatic Helicobacter species to a
      greater extent than heparin, 60-90% inhibition vs 30-70% inhibition by heparin.
      Identification of receptors that EHS ligands bind to is important for
      understanding the development of infection and may provide a rational target to
      prevent infection and therapy.

PMID- 21088931
TI  - Bioartificial liver devices: Perspectives on the state of the art.
AB  - Acute liver failure remains a significant cause of morbidity and mortality.
      Bioartificial liver (BAL) devices have been in development for more than 20
      years. Such devices aim to temporarily take over the metabolic and excretory
      functions of the liver until the patients' own liver has recovered or a donor
      liver becomes available for transplant. The important issues include the choice
      of cell materials and the design of the bioreactor. Ideal BAL cell materials
      should be of good viability and functionality, easy to access, and exclude
      immunoreactive and tumorigenic cell materials. Unfortunately, the current cells
      in use in BAL do not meet these requirements. One of the challenges in BAL
      development is the improvement of current materials; another key point concerning
      cell materials is the coculture of different cells. The bioreactor is an
      important component of BAL, because it determines the viability and function of
      the hepatocytes within it. From the perspective of bioengineering, a successful
      and clinically effective bioreactor should mimic the structure of the liver and
      provide an in vivo-like microenvironment for the growth of hepatocytes, thereby
      maintaining the cells' viability and function to the maximum extent. One future
      trend in the development of the bioreactor is to improve the oxygen supply
      system. Another direction for future research on bioreactors is the application
      of biomedical materials. In conclusion, BAL is, in principle, an important
      therapeutic strategy for patients with acute liver failure, and may also be a
      bridge to liver transplantation. It requires further research and development,
      however, before it can enter clinical practice.

PMID- 21088932
TI  - Turning Muller glia into neural progenitors in the retina.
AB  - Stimulating neuronal regeneration is a potential strategy to treat sight
      threatening diseases of the retina. In some classes of vertebrates, retinal
      regeneration occurs spontaneously to effectively replace neurons lost to acute
      damage in order to restore visual function. There are different mechanisms and
      cellular sources of retinal regeneration in different species, include the
      retinal pigmented epithelium, progenitors seeded across the retina, and the
      Muller glia. This review briefly summarizes the different mechanisms of retinal
      regeneration in frogs, fish, chicks, and rodents. The bulk of this review
      summarizes and discusses recent findings regarding regeneration from Muller glia
      derived progenitors, with emphasis on findings in the chick retina. The Muller
      glia are a promising source of regeneration-supporting cells that are intrinsic
      to the retina and significant evidence indicated these glias can be stimulated to
      produce neurons in different classes of vertebrates. The key to harnessing the
      neurogenic potential of Muller glia is to identify the secreted factors,
      signaling pathways, and transcription factors that enable de-differentiation,
      proliferation, and neurogenesis. We review findings regarding the roles of
      mitogen-activated protein kinase and notch signaling in the proliferation and
      generation of Muller glia-derived retinal progenitors.

PMID- 21088933
TI  - Ca(v)1.3 and BK channels for timing and regulating cell firing.
AB  - L-type Ca(2+) channels (LTCCs, Ca(v)1) open readily during membrane
      depolarization and allow Ca(2+) to enter the cell. In this way, LTCCs regulate
      cell excitability and trigger a variety of Ca(2+)-dependent physiological
      processes such as: excitation-contraction coupling in muscle cells, gene
      expression, synaptic plasticity, neuronal differentiation, hormone secretion, and
      pacemaker activity in heart, neurons, and endocrine cells. Among the two major
      isoforms of LTCCs expressed in excitable tissues (Ca(v)1.2 and Ca(v)1.3),
      Ca(v)1.3 appears suitable for supporting a pacemaker current in spontaneously
      firing cells. It has steep voltage dependence and low threshold of activation and
      inactivates slowly. Using Ca(v)1.3(-/-) KO mice and membrane current recording
      techniques such as the dynamic and the action potential clamp, it has been
      possible to resolve the time course of Ca(v)1.3 pacemaker currents that regulate
      the spontaneous firing of dopaminergic neurons and adrenal chromaffin cells. In
      several cell types, Ca(v)1.3 is selectively coupled to BK channels within
      membrane nanodomains and controls both the firing frequency and the action
      potential repolarization phase. Here we review the most critical aspects of
      Ca(v)1.3 channel gating and its coupling to large conductance BK channels
      recently discovered in spontaneously firing neurons and neuroendocrine cells with
      the aim of furnishing a converging view of the role that these two channel types
      play in the regulation of cell excitability.

PMID- 21088935
TI  - Falciparum malaria in children-a brief report of 305 patients from rourkela,
      eastern India.
AB  - Most of the studies on malaria in children are reported from Africa, but only a
      few are from India. A retrospective study of 305 children with slide positive
      malaria was conducted at Rourkela, Orissa. 5.2% children were below 1 year of
      age. 34.1% were between 1 and 5 years and 60.7% were above 5 years. 63.9% were
      boys. The presenting symptoms were fever (98.4%), vomiting (52%), and headache
      (22%). 121 patients had one or more complications viz., cerebral malaria (n =
      56), severe anemia (39), jaundice (31), convulsions (20), hypoglycemia (10) and
      only one with acute renal failure. 22 patients died.

PMID- 21088934
TI  - Inhibition of obesity-induced hepatic ER stress by early insulin therapy in obese
      diabetic rats.
AB  - To understand the mechanism by which early insulin therapy improves insulin
      sensitivity in type 2 diabetes, we investigated endoplasmic reticulum (ER) stress
      in the liver of type 2 diabetic rats. A high fat diet plus a low dose of
      streptozotocin (STZ) in Sprague-Dawley (SD) rats was implemented to create an
      animal model mimicking diabetes. After 3 weeks of insulin treatment, the rats
      were examined for insulin sensitivity and ER stress in the liver. To investigate
      insulin sensitivity within the liver, serine phosphorylation of IRS-1 (Ser307)
      and Akt (Ser473) and expression of gluconeogenic genes, PEPCK and G6Pase, were
      tested. Protein levels of ER stress markers, such as immunoglobulin binding
      protein (Bip), inositol-requiring protein 1 alpha (IRE1alpha), and unspliced and
      spliced x-box binding protein-1 (XBP-1), were determined to assess ER stress. In
      the diabetic (DM) group, IRS-1 phosphorylation was increased (P < 0.05), Akt
      phosphorylation was reduced (P < 0.05), expression of PEPCK and G6Pase was
      elevated (P < 0.05), and ER stress markers were up-regulated (P < 0.05) relative
      to the non-diabetic rats. In the insulin (INS) therapy group, all of
      aforementioned changes were attenuated or reversed (P < 0.05). In addition, c-Jun
      N-terminal kinase (JNK) activity and SREBP-1 expression were decreased (P <
      0.05). Adipose tissue mass was increased (P < 0.05). These data suggest that
      short-term insulin therapy relieved ER stress and enhanced insulin sensitivity in
      the liver of diabetic rats. The mechanism is likely related to fat redistribution
      from liver to adipose tissue. These cellular and molecular responses may
      represent a mechanism for improvement of insulin sensitivity in type 2 diabetic
      rats by insulin therapy.

PMID- 21088936
TI  - Normal variants of bowel FDG uptake in dual-time-point PET/CT imaging.
AB  - OBJECTIVE: To evaluate the normal variants of the physiological bowel 2-deoxy-2
      [(18)F]fluoro-D-glucose (FDG) uptake in dual-time-point positron emission
      tomography/computed tomography (PET/CT). METHODS: We performed a retrospective
      review of 206 consecutive asymptomatic subjects who underwent whole-body FDG
      PET/CT for medical checkup in our institution. The criteria for exclusion of the
      subjects from this study were as follows: history of abdominal surgeries or
      endoscopic mucosal resection, history of any malignant tumors, symptoms of
      diarrhea or constipation, a positive fecal occult blood test, elevated serum
      carcinoembryonic antigen (CEA) level, and hyperglycemia (more than 110 mg/dl). A
      total of 39 subjects (32 males, 7 females, mean age 58.1 years old) were enrolled
      in this retrospective study. Two radiologists evaluated the dual-time-point FDG
      PET/CT images of these 39 subjects, retrospectively. FDG uptakes in 5 areas
      (small bowel (SB), cecum and ascending colon (AC), transverse colon (TC),
      descending colon (DC), and rectosigmoid colon (RS)) were scored visually in
      comparison with the activity in the liver (0 = no uptake, 1 = activity less than
      that in the liver, and 2 = activity equal to or greater than that in the liver)
      in the early and delayed image. The scores decided by two radiologists were
      averaged and this average score was defined as the bowel uptake score (BUS). For
      34 areas with the BUS of 2 in either the early or delayed images, the maximum
      standardized uptake values (SUV(max)) were measured for semiquantitative
      analysis. Wilcoxon's signed rank test and paired t test were adopted for the
      statistical analyses. RESULTS: The average BUS in the early/delayed images was
      1.19/1.17 (SB), 0.81/1.23 (AC), 0.10/0.35 (TC), 0.35/0.59 (DC), and 1.17/1.54
      (RS), respectively. The average SUV(max) of the 34 areas with a score of 2 was
      3.11 in the early images and 3.76 in the delayed images. The scores in the AC,
      TC, DC and RS, and the SUV(max) were significantly higher in the delayed images
      (p < 0.05). CONCLUSIONS: Physiological FDG uptake in the colon increases
      significantly from the early to the delayed phase in dual-time-point PET/CT
      imaging, which should be carefully taken into consideration in the diagnosis of
      bowel diseases.

PMID- 21088938
TI  - New advances in benign prostatic hyperplasia: laser therapy.
AB  - Throughout the past decade, numerous techniques for the treatment of benign
      prostatic hyperplasia have emerged. Laser therapy, in particular, has gained
      widespread popularity among urologists. Since its inception in 1996, holmium
      laser enucleation of the prostate (HoLEP) has been evaluated rigorously in the
      treatment of glands of all sizes. HoLEP has produced superior relief of bladder
      outlet obstruction as compared to transurethral resection of the prostate based
      on urodynamics, and has proved equally as effective as open prostatectomy, for
      the management of very large glands (>100 cc), with lower morbidity. In addition
      to HoLEP, several newer but less well-studied laser techniques currently are
      available. These include photoselective laser vaporization utilizing the
      potassium-titanyl-phosphate (KTP or "green light") laser, thulium laser
      enucleation, and high-power diode laser vaporization. This report reviews the
      most current literature on laser therapies utilized in the treatment of benign
      prostatic hyperplasia with regards to safety, outcome, efficiency, and long-term
      durability.

PMID- 21088937
TI  - Use of diagnostic testing to detect infertility.
AB  - The evaluation of the infertile male continues to be a clinical challenge of
      increasing significance with considerable emotional and financial burdens. Many
      physiological, environmental and genetic factors are implicated; however, the
      etiology of suboptimal semen quality is poorly understood. This review focuses on
      the diagnostic testing currently available, as well as future directions that
      will be helpful for the practicing urologist and other clinicians to fully
      evaluate the infertile male.

PMID- 21088939
TI  - Clinico-pathologic conference: case 3. Calcifying cystic odontogenic tumor
      (CCOT).

PMID- 21088940
TI  - Clinico-pathologic conference: case 4. Langerhans cell histiocytosis (LCH).
AB  - A 13-month-old Japanese boy presented with painless swelling in a left mandible
      and cheek. Intraoral examination revealed swelling in the left mandible and
      hemorrhage of oral mucosa due to biting. CT images revealed a wide osteolytic
      lesion of the left mandible with floating teeth. Biopsy was carried out and
      histopathological diagnosis was discussed.

PMID- 21088941
TI  - Clinico-pathologic conference: case 5. Dentinogenic ghost cell tumour (DGCT).

PMID- 21088942
TI  - Etoposide, mitomycin, and methotrexate combination in heavily treated breast
      cancer: a retrospective study.
AB  - BACKGROUND: Since 2004, metastatic breast cancer patients pretreated with
      anthracyclines, taxanes, and capecitabine have been treated in our institution
      with a combination of mitomycin C, methotrexate, and VP-16 (VMM). We report in
      this study a retrospective analysis of the activity and safety of the VMM
      combination. METHODS: Patients were treated with a combination of VP-16 (100
      mg/m2 on day 1), mitomycin C (MMC, 10 mg/m2 on day 1), and methotrexate (MTX,
      12.5 mg/m2 twice a day on day 2 and 3) in a 21-day cycle. RESULTS: Seventy-five
      patients were treated. Median age was 48 years. A total of 256 cycles were
      administered. Median relative dose intensities were 0.87, 0.87, and 0.95 for VP
      16, MMC, and MTX, respectively. Objective response rate was 31%, with a clinical
      benefit rate of 47%. Median response duration was 5.8 months. Median disease
      stabilization duration was 9.1 months. Median progression-free survival (PFS) was
      4.2 months with a 14% 1-year PFS rate. Median overall survival (OS) was 6.2
      months, with a 25% 1-year OS rate. Myelosuppression was the most common toxicity.
      The most commonly reported extra-hematological adverse event (AE) was fatigue.
      Emesis and alopecia were rarely reported. CONCLUSIONS: This combination appears
      to be effective and well tolerated in this heavily pretreated metastatic breast
      cancer population.

PMID- 21088943
TI  - In vivo assessment of parenteral formulations of oligo(3-hydroxybutyric Acid)
      conjugates with the model compound Ibuprofen.
AB  - Polymer-drug conjugates have gained significant attention as pro-drugs releasing
      an active substance as a result of enzymatic hydrolysis in physiological
      environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a
      carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a
      potential pro-drug for parenteral administration. Two different formulations, an
      oily solution and an o/w emulsion were prepared and administered intramuscularly
      (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The
      concentration of ibuprofen in blood plasma was analysed by HPLC, following solid
      phase extraction and using indometacin as internal standard (detection limit,
      0.05 microg/ml). No significant differences in the pharmacokinetic parameters (C
      (max), T (max), AUC) were observed between the two tested formulations of the 3
      hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily
      solution, the relative bioavailability of ibuprofen conjugates from oily
      solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3
      hydroxybutyric acid formulations released the active substance over a
      significantly extended period of time with ibuprofen still being detectable 24 h
      post-injection, whereas the free compound was almost completely eliminated as
      early as 6 h after administration. The conjugates remained in a muscle tissue for
      a prolonged time and can hence be considered as sustained release systems for
      carboxylic acid derivatives.

PMID- 21088944
TI  - In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine
      tablets and determination of tablet coating thickness.
AB  - INTRODUCTION: Substantial variability in gastrointestinal pH is observed in
      patients with ulcerative colitis (UC). We characterized the effect of pH on 5
      aminosalicylic acid (5-ASA) release from MMX mesalamine tablets (Shire
      Pharmaceuticals Inc., Wayne, PA, USA), examined thickness/uniformity of tablet
      film coatings, and explored the influence of simulating altered gastrointestinal
      motility. METHODS: Nondestructive, three-dimensional, terahertz pulse imaging
      (TPI) was used to characterize the film coating of three lots of MMX mesalamine
      tablets (n=36). Thereafter, 5-ASA release from these tablets was evaluated using
      United States Pharmacopeia (USP) apparatus II at pH 6.8 and 7.2. Onset of tablet
      film-coat breach and mean dissolution time were determined for each lot. 5-ASA
      release was also assessed at three different paddle rotation speeds (50, 75, and
      100 rpm) at pH 7.2. RESULTS: The mean +/- SD film-coating thickness of the three
      lots of MMX mesalamine tablets were 109.2 +/- 16.8, 113.1 +/- 19.5, and 113.8 +/-
      19.8 MUM, respectively. At pH 6.8 (100 rpm), the onset of film-coat breach was 10
      30 minutes, whereas at pH 7.2 this was observed within 10 minutes. 5-ASA release
      was uniform at both pH conditions, with minimal lot-to-lot variability. Complete
      drug release was achieved within 6 hours under both pH conditions. 5-ASA release
      increased in proportion with paddle speed, but remained prolonged at all speeds.
      CONCLUSION: 5-ASA release from MMX mesalamine is unaffected by normal variations
      in simulated intracolonic pH. The dissolution profile of 5-ASA from MMX
      mesalamine tablets may be attributed to consistent outer film coatings and the
      hydrogel-forming matrix that controls the drug release after dissolution of the
      film coating.

PMID- 21088945
TI  - Model-based design of mechanical therapies for myocardial infarction.
AB  - The mechanical properties of healing myocardial infarcts are a critical
      determinant of pump function and the transition to heart failure. Recent reports
      suggest that modifying infarct mechanical properties can improve function and
      limit ventricular remodeling. However, little attempt has been made to identify
      the specific infarct material properties that would optimize left ventricular
      (LV) function. We utilized a finite-element model of a large anteroapical infarct
      in a dog heart to explore a wide range of infarct mechanical properties.
      Isotropic stiffening of the infarct reduced end-diastolic (EDV) and end-systolic
      (ESV) volumes, improved LV contractility, but had little effect on stroke volume.
      A highly anisotropic infarct, with high longitudinal stiffness but low
      circumferential stiffness coefficients, produced the best stroke volume by
      increasing diastolic filling, without affecting contractility or ESV. Simulated
      infarcts in two different locations displayed different transmural strain
      patterns. Our results suggest that there is a general trade-off between acutely
      reducing LV size and acutely improving LV pump function, that isotropically
      stiffening the infarct is not the only option of potential therapeutic interest,
      and that customizing therapies for different infarct locations may be important.
      Our model results should provide guidance for design and development of therapies
      to improve LV function by modifying infarct mechanical properties.

PMID- 21088947
TI  - [Sixth one-day convention held by the Antilles-Guiana Committee Exotic Pathology
      Society in Cayenne on 27 November 2009. Coupled with the second one-day
      scientific convention of the Antilles-Guiana CIC-EC (Inserm)].

PMID- 21088946
TI  - Generation of pig iPS cells: a model for cell therapy.
AB  - Reprogramming of pig somatic cells to induced pluripotent stem cells provides a
      tremendous advance in the field of regenerative medicine since the pig represents
      an ideal large animal model for the preclinical testing of emerging cell
      therapies. However, the current generation of pig-induced pluripotent stem cells
      (piPSCs) require the use of time-consuming and laborious retroviral or lentiviral
      transduction approaches, in order to ectopically express the pluripotency
      associated transcription factors Oct4, Sox2, Klf4 and c-Myc, in the presence of
      feeder cells. Here, we describe a simple method to produce piPSC with a single
      transfection of a CAG-driven polycistronic plasmid expressing Oct4, Sox2, Klf4, c
      Myc and a green fluorescent protein (GFP) reporter gene, in gelatine-coated
      plates, with or without feeder cells. In our system, the derivation of piPSCs
      from adult pig ear fibroblasts on a gelatine coating showed a higher efficiency
      and rate of reprogramming when compared with three consecutive retroviral
      transductions of a similar polycistronic construct. Our piPSCs expressed the
      classical embryonic stem cell markers, exhibit a stable karyotype and formed
      teratomas. Moreover, we also developed a simple method to generate in vitro
      spontaneous beating cardiomiocyte-like cells from piPSCs. Overall, our
      preliminary results set the bases for the massive production of xeno-free and
      integration-free piPSCs and provide a powerful tool for the preclinical
      application of iPSC technology in a large animal setting.

PMID- 21088948
TI  - [Clinical characteristics, progression and risk factors of geographic atrophy].
AB  - Geographic atrophy (GA) as the late stage manifestation of age-related macular
      degeneration (AMD) is a progressive disease process afflicting the retinal
      pigment epithelium, choriocapillaris and the outer neurosensory retina. GA
      represents a complex, multifactorial disease governed by the interdependence of
      genetic, endogenous and exogenous factors. Diagnosis and monitoring of GA
      progression is largely based on various retinal imaging modalities. After the
      breakthrough in the treatment of wet AMD GA represents a large clinical
      challenge. Recent studies have contributed to a better understanding of the
      pathophysiological pathways, natural history and predictive markers for
      progression.

PMID- 21088949
TI  - [Imaging diagostics of geographic atrophy].
AB  - The development of imaging technologies has contributed to the understanding of
      the genesis and pathophysiological mechanisms of geographic atrophy (GA)
      secondary to age-related macular degeneration (AMD). Fundus autofluorescence
      (FAF) imaging allows accurate discrimination of the boundaries of atrophic
      patches. Furthermore, predictive markers for disease progression can be
      identified. Non-invasive FAF imaging now represents the gold standard for
      evaluating progressive enlargement of atrophic areas. By means of high resolution
      optical coherence tomography (OCT) microstructural retinal changes in GA can be
      identified. Anatomical endpoints are now being used in interventional GA trials
      and represent meaningful outcome parameters as surrogate markers in an overall
      slowly progressive disease which may not affect the fovea until later stages of
      the disease.

PMID- 21088950
TI  - [Therapy approaches for geographic atrophy].
AB  - Geographic atrophy, the dry form and late manifestation of age-related macular
      degeneration, is the next challenge following the breakthrough in the treatment
      of neovascular age-related macular degeneration (AMD). Various interventional
      pharmacologic approaches with different targets are already being tested in
      clinical interventional trials. These include reduction of retinal toxins, anti
      inflammatory agents, complement inhibition, neuroprotection and alleviation of
      oxidative stress. Until efficacy and safety is demonstrated, aids for poor vision
      and further rehabilitative measures remain essential for patients with advanced
      dry AMD.

PMID- 21088951
TI  - [Procedural guidelines. Good practice procedures for acquisition and preparation
      of cryopreserved human amniotic membranes from donor placentas].
AB  - A cornea/tissue bank must have an organizational structure in which
      responsibility and authority to issue directives are clearly defined. It must
      also use a documented quality management system on the basis of good practice
      procedures which is maintained to the current standards. The personnel of a
      cornea/tissue bank must be present in sufficient numbers and be suitably
      qualified. A cornea/tissue bank must be in possession of appropriate facilities
      which are suitable for the main purpose of preparation of cryopreserved human
      amniotic membranes from donor placentas. All equipment must be designed and
      maintained corresponding to the intended purpose. Deviations from the stipulated
      quality and safety standards must give rise to documented investigations which
      include decisions on options for correctional and preventive measures.
      Acquisition of donors and tissue sampling must be strictly controlled and
      documented. This also applies to entry of donor tissue in the cornea/tissue bank.
      Cryopreserved human amniotic membranes can only be preserved from donors
      undergoing caesarean section and who did not present any known infection of the
      abdominal cavity or any systemic blood borne infection. Contamination of media
      used for cryopreservation of donor placenta must be ruled out at least once.
      Measures must be taken to keep the risk of contamination as low as possible.
      Cryopreserved human amniotic membranes from donor placentas can only be released
      if defined criteria are fulfilled. Any suspicion of severe undesired reactions
      and events for the recipient of an amniotic membrane transplant must be
      registered with the authorities. The activities of a cornea/tissue bank must
      maintain and adapt to the state-of-the-art with respect to scientific progress.

PMID- 21088952
TI  - [The value of acetylsalicylic acid in retinal vein occlusion].

PMID- 21088954
TI  - [Perioperative management of long-term medication].
AB  - Anesthesiologists and surgeons are increasingly faced with patients who are under
      long-term medication. Some of these drugs can interact with anaesthetics or
      anaesthesia and/or surgical interventions. As a result, patients may experience
      complications such as bleeding, ischemia, infection or severe circulatory
      reactions. On the other hand, perioperative discontinuation of medication is
      often more dangerous. The proportion of outpatient operations has increased
      dramatically in recent years and will probably continue to increase. Since the
      implementation of DRGs (pending in Switzerland, introduced in Germany for some
      time), the patient enters the hospital the day before operation. This means that
      the referring physician as well as anesthesiologists and surgeons at an early
      stage must deal with issues of perioperative pharmacotherapy. This review article
      is about the management of the major drug classes during the perioperative
      period. In addition to cardiac and centrally acting drugs and drugs that act on
      hemostasis and the endocrine system, special cases such as immunosuppressants and
      herbal remedies are mentioned.

PMID- 21088955
TI  - [Injuries and dysfunction of the posterior tibial tendon].
AB  - The function of the posterior tibial (PT) tendon is to stabilize the hindfoot
      against valgus and eversion forces. It functions as the primary invertor of the
      foot and assists the Achilles tendon in plantar flexion. The PT tendon is a
      stance phase muscle, firing from heel strike to shortly after heel lift-off. It
      decelerates subtalar joint pronation after heel contact. It functions as a
      powerful subtalar joint supinator and as a support of the medial longitudinal
      arch. The action of the tendon travels to the transverse tarsal joints, locking
      them and allowing the gastrocnemius to support heel rise. Acute injuries of the
      PT tendon are rare and mostly affect the active middle-aged patient or they are
      the result of complex injuries to the ankle joint complex. Dysfunction of the PT
      tendon following degeneration and rupture, in contrast, has shown an increasing
      incidence in recent years. To which extent changed lifestyle, advancing age,
      comorbidities, and obesity play a role has not yet been clarified in detail.
      Dysfunction of the PT tendon results in progressive destabilization of the hind-
      and midfoot. Clinically, the ongoing deformation of the foot can be classified
      into four stages: in stage 1, the deformity is distinct and fully correctable; in
      stage II, the deformity is obvious, but still correctable; in stage III, the
      deformity has become stiff; and in stage IV, the ankle joint is also involved in
      the deformity. Treatment modalities depend on stage: while conservative measures
      may work in stage I, surgical treatment is mandatory for the later stages.
      Reconstructive surgery is advised in stage II, whereas in stage III and IV
      correcting and stabilizing arthrodeses are advised. A promising treatment option
      for stage IV may be adding an ankle prosthesis to a triple arthrodesis, as long
      as the remaining competence of the deltoid ligament is sufficient. An appropriate
      treatment is mandatory to avoid further destabilization and deformation of the
      foot. Failures of treatment result mostly from underestimation of the problem or
      insufficient treatment of existing instability and deformity.

PMID- 21088956
TI  - [Proximal and distal rupture of the m. biceps brachii].
AB  - Ruptures of the biceps tendon account for a high percentage of tendon ruptures.
      The aetiology of proximal ruptures of the long head of the biceps tendon is often
      degenerative and they are frequently associated with lesions of the rotator cuff.
      The clinical findings are often not specific and long lasting. Distal ruptures of
      the biceps tendon mostly occur during eccentric contraction of the biceps
      muscle.Clinical tests, the associated haematoma and a distalisation or
      proximalisation of the muscle belly in combination with ultrasound or MRI to rule
      out combined diseases lead to the diagnosis. The possible options include
      conservative and operative treatment. Tenotomy and tenodesis lead to comparable
      results in the literature. Therefore, conservative treatment is mostly
      recommended in proximal ruptures. Operative treatment is preferred in distal
      ruptures of the biceps tendon in order to achieve an anatomical reconstruction of
      the muscle function. Chronic ruptures of the distal biceps tendon can be
      successfully treated with free autografts or allografts.

PMID- 21088957
TI  - Asenapine improves phencyclidine-induced object recognition deficits in the rat:
      evidence for engagement of a dopamine D1 receptor mechanism.
AB  - RATIONALE: Cognitive deficits are common in schizophrenia. Asenapine is an
      atypical antipsychotic approved by the US Food and Drug Administration in adults
      for treatment of schizophrenia or acute treatment, as monotherapy or adjunct
      therapy to lithium or valproate, of manic or mixed episodes of bipolar I
      disorder. OBJECTIVES: Based on the receptor pharmacology of asenapine, the
      current study assessed the efficacy and mechanism of action of asenapine to
      improve a subchronic phencyclidine (PCP)-induced deficit in visual recognition
      memory using the novel object recognition (NOR) paradigm in the rat, a paradigm
      of relevance to cognition in schizophrenia. METHODS: Female-hooded Lister rats
      received vehicle or PCP (2 mg/kg, i.p.) for 7 days, followed by a 7-day washout.
      On the test day, rats were given asenapine (0.001-0.1 mg/kg, s.c.) alone or in
      combination with the D(1) receptor antagonist SCH-23390 (0.05 mg/kg, i.p.) or 5
      HT(1A) receptor antagonist WAY100635 (1 mg/kg, i.p.). Time spent exploring two
      identical objects during a 3-min acquisition trial (followed by a 1-min
      intertrial interval) and then a familiar and a novel object for another 3 min
      (retention trial) were recorded onto videotape and scored blind. RESULTS: In the
      retention trial, vehicle- but not PCP-treated animals explored the novel object
      significantly more than the familiar object (p < 0.001). Asenapine (0.01-0.075
      mg/kg) reversed PCP-induced deficits in NOR (p < 0.01-0.001) in a dose-related
      manner. This effect was antagonised by SCH-23390 but not by WAY100635.
      CONCLUSIONS: These results demonstrate a role for D(1) but not 5-HT(1A) receptor
      mechanisms in mediating the cognitive effects of asenapine in this rodent model.

PMID- 21088959
TI  - Peripheral biomarkers of cognitive response to dopamine receptor agonist
      treatment.
AB  - RATIONALE: Using biological markers to objectively measure addiction severity or
      to identify individuals who might benefit most from pro-cognitive treatment could
      potentially revolutionize neuropsychopharmacology. We investigated the use of
      dopamine receptor mRNA levels in circulating blood cells as predictors of
      cognitive response following dopamine agonist treatment, and as biomarkers of the
      severity of stimulant drug dependence. METHODOLOGY: We employed a double-blind,
      placebo-controlled cross-over design, administering a single dose of the
      selective dopamine D(2/3) receptor agonist pramipexole (0.5 mg) to increase
      dopamine transmission in one session and a placebo treatment in another session
      in 36 volunteers. Half the volunteers had a formal diagnosis of stimulant
      dependence, while half had no psychiatric history. Participants performed
      neurocognitive tests from the CANTAB battery on both occasions, and stimulant
      dependent individuals rated drug craving using visual analog scales. Whole-blood
      mRNA levels were measured for three dopamine-related genes: DRD3 and DRD4
      (dopamine receptors), and catechol-O-methyltransferase (COMT; a dopamine
      catabolic enzyme). RESULTS: Stimulant users performed worse than healthy
      volunteers on the cognitive tests. The variation in peripheral dopamine D(3)
      receptor mRNA expression explained over one quarter of the variation in response
      to pramipexole on the spatial working memory test across all participants. The
      severity of stimulant dependence was also significantly associated with
      peripheral COMT mRNA expression in stimulant users. CONCLUSIONS: Peripheral
      expression of dopamine-related genes may be useful as a biomarker of cognitive
      response to dopamine agonist drugs and of severity of addiction to dopamine
      releasing stimulant drugs.

PMID- 21088958
TI  - Functional topography of midbrain and pontine serotonergic systems: implications
      for synaptic regulation of serotonergic circuits.
AB  - RATIONALE: Dysfunction of serotonergic systems is thought to play an important
      role in a number of neurological and psychiatric disorders. Recent studies
      suggest that there is anatomical and functional diversity among serotonergic
      systems innervating forebrain systems involved in the control of physiologic and
      behavioral responses, including the control of emotional states. OBJECTIVE: Here,
      we highlight the methods that have been used to investigate the heterogeneity of
      serotonergic systems and review the evidence for the unique anatomical,
      hodological, and functional properties of topographically organized
      subpopulations of serotonergic neurons in the midbrain and pontine raphe complex.
      CONCLUSION: The emerging understanding of the topographically organized synaptic
      regulation of brainstem serotonergic systems, the topography of the efferent
      projections of these systems, and their functional properties, should enable
      identification of novel therapeutic approaches to treatment of neurological and
      psychiatric conditions that are associated with dysregulation of serotonergic
      systems.

PMID- 21088960
TI  - Selective breeding for magnitude of methamphetamine-induced sensitization alters
      methamphetamine consumption.
AB  - RATIONALE: Genetically determined differences in susceptibility to drug-induced
      sensitization could be related to risk for drug consumption. OBJECTIVES: Studies
      were performed to determine whether selective breeding could be used to create
      lines of mice with different magnitudes of locomotor sensitization to
      methamphetamine (MA). MA sensitization (MASENS) lines were also examined for
      genetically correlated responses to MA. METHODS: Beginning with the F2 cross of
      C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to
      repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization.
      Five selected offspring generations were tested. All generations were also tested
      for MA consumption, and some were tested for dose-dependent locomotor-stimulant
      responses to MA, consumption of saccharin, quinine, and potassium chloride as a
      measure of taste sensitivity, and MA clearance after acute and repeated MA.
      RESULTS: Selective breeding resulted in creation of two lines [MA high
      sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in
      magnitude of MA-induced sensitization. Initially, greater MA consumption in
      MAHSENS mice reversed over the course of selection so that MALSENS mice consumed
      more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant
      effects of MA, but there were no significant differences between the lines in MA
      clearance from blood. CONCLUSIONS: Genetic factors influence magnitude of MA
      induced locomotor sensitization and some of the genes involved in magnitude of
      this response also influence MA sensitivity and consumption. Genetic factors
      leading to greater MA-induced sensitization may serve a protective role against
      high levels of MA consumption.

PMID- 21088963
TI  - Questionable direct association between ictal activity and thalamus lesions.

PMID- 21088962
TI  - The correlation between carotid siphon calcification and lacunar infarction.
AB  - INTRODUCTION: The aim of this study was to evaluate the correlation between
      carotid siphon (CS) calcification and lacunar infarction caused by small-vessel
      disease. METHODS: This retrospective study included 445 patients (M/F = 256:189)
      older than 40 years (mean age 60.0 +/- 12.3 years, range 41-98 years) without
      large intracranial lesions who had undergone both brain CT and MRI within an
      interval of 6 months. The patients were classified into three groups according to
      the number of lacunar infarctions: group I-zero infarctions (n = 328), group II
      one to three infarctions (n = 94), and group III-four or more infarctions (n =
      23). The severity of CS calcification was evaluated on CT and scored on a five
      point scale (0-none, 1-stippled, 2-thin continuous or thick discontinuous, 3
      thick continuous, 4-double tracts), and the calcification scores on both sides
      were summed. An ANOVA test was used to compare calcification scores among the
      three groups, and a logistic regression test was used to evaluate the influence
      of CS calcification and known cerebrovascular risk factors on the occurrence of
      lacunar infarction. RESULTS: On the ANOVA test, total calcification scores were
      significantly different among the three groups (group I = 1.28 +/- 1.99, group II
      = 3.31 +/- 2.39, group III = 4.36 +/- 2.08; P < 0.05). Higher rates of lacunar
      infarction were associated with higher CS calcification scores. On the logistic
      regression test, CS calcification, age, and hypertension were significant risk
      factors for lacunar infarction (P < 0.05). CONCLUSION: CS calcification was
      correlated with the occurrence of lacunar infarction. The degree of CS
      calcification may be used to predict the possibility of a future lacunar
      infarction.

PMID- 21088964
TI  - Linear stent-assisted coiling: another way to treat very wide-necked intracranial
      aneurysms.
AB  - We report a new technique of "linear" stent-assisted coiling for the endovascular
      treatment (EVT) of a large and very wide-necked unruptured middle cerebral artery
      (MCA) bifurcation aneurysm in a 45-year-old man. Two self-expandable stents were
      delivered within the MCA bifurcation branches with both proximal stent ends
      facing each other within the MCA bifurcation. Thanks to this linear stents
      placement, complete aneurysm neck coverage was obtained in order to safely coil
      the sac.

PMID- 21088961
TI  - Potential programming of dopaminergic circuits by early life stress.
AB  - Stress and high levels of glucocorticoids during pre- and early postnatal life
      seem to alter developmental programs that assure dopaminergic transmission in the
      mesolimbic, mesocortical, and nigrostriatal systems. The induced changes are
      likely to be determined by the ontogenetic state of development of these brain
      regions at the time of stress exposure and their stability is associated with
      increased lifetime susceptibility to psychiatric disorders, including drug
      addiction. This article is intended to serve as a starting point for future
      studies aimed at the attenuation or reversal of the effects of adverse early life
      events on dopamine-regulated behaviors.

PMID- 21088966
TI  - Rituximab in patients with refractory autoimmune hemolytic anemia.

PMID- 21088965
TI  - Adoptive cell therapy of prostate cancer using female mice-derived T cells that
      react with prostate antigens.
AB  - In this study, we report a novel treatment strategy that could potentially be
      used to improve efficacy of adoptive cell therapy for patients with prostate
      cancer. We show that female C57BL/6 mice are able to effectively reject two
      syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The
      protective antitumor immunity appears to primarily involve T cell responses
      reactive against general prostate tumor/tissue antigens, rather than simply to
      male-specific H-Y antigen. For the first time we show that adoptive transfer of
      lymphocytes from TRAMP-C2-primed or naive female mice effectively control
      prostate tumor growth in male mice, when combined with host pre-conditioning
      (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No
      pathological autoimmune response was observed in the treated tumor-bearing male
      mice. Our studies provide new insights regarding the immune-mediated recognition
      of male-specific tissue, such as the prostate, and may offer new immunotherapy
      treatment strategies for advanced prostate cancer.

PMID- 21088967
TI  - Pilot study of pegylated interferon alpha-2a treatment during chemo- and
      radiotherapy and post-remission maintenance in patients with EBV-positive
      extranodal NK/T cell lymphoma.
AB  - The role of the Epstein-Barr virus (EBV) in the pathogenesis of extranodal
      natural killer/T-cell lymphoma (ENKTCL), and its resistance to chemotherapy
      raises the possibility of antiviral therapeutic strategies. The aim of this
      prospective pilot study was to evaluate the feasibility and effectiveness of
      antiviral treatment using pegylated interferon alpha-2a (pIFN alpha-2a) as an
      adjunct to induction and maintenance therapy in patients with ENKTCL. A total of
      seven patients with newly diagnosed EBV-positive ENKTCL were enrolled. Pegylated
      IFN alpha-2a was administered during induction chemoradiotherapy. If patients
      achieved a partial or complete response (PR or CR, respectively), high-dose
      chemotherapy with autologous stem cell transplantation (HDT/SCT) was given. After
      transplantation, maintenance therapy included pIFN alpha-2a for 3 years. Of the
      patients available for evaluation, all achieved a CR or PR after induction
      therapy but one patient relapsed before HDT/SCT. The event free survival and
      overall survival at 3 years were 50.0 +/- 20.4% and 66.7 +/- 19.2%, respectively.
      The 3-year disease-free survival after transplantation of the patients that
      received maintenance therapy was 80.0 +/- 17.9%. The results of this pilot study
      indicated that pIFN alpha-2a containing induction and maintenance therapy was
      feasible and effective for ENKTCL.

PMID- 21088968
TI  - [Biomarkers collections: the future or a waste of resources?].
AB  - Disease biomarkers would aim at a more specific definition of diagnosis or
      subtype of a certain disease, as well as prognosis definition, including efficacy
      and side effects of certain therapeutics. Biomarkers could lead to a
      prognostically optimized definition of remission in the individual patient and
      thus to a more objective definition of therapeutic efficacy. Is this possible and
      does it make sense? Or would an extensive analysis of biomarkers to date lead to
      a costly overestimation of as yet not well established biologic parameters?
      Although we are currently unable to answer this question, many colleagues argue
      in favour of more in depth research for a better evaluation of biomarkers in many
      diseases. This could save money if we were able to predict the efficacy of
      expensive drugs such as immunobiologics. Biomarkers comprise cytometric
      information, data on protein expression and secretion, mRNA, microRNA or DNA,
      including epigenetic variants. Although much of these data already exist in the
      scientific literature, it is associated with problems in terms of feasibility
      (for cytometry and RNA analysis only on-site analysis is possible, while for DNA
      analysis central testing is also possible), costs and reproducibility (ethnic
      variability!). To date all biomarkers have only limited value in terms of the
      above-mentioned aims. The present review compiles "PROs and CONs" in a subjective
      way in order to provoke a discussion on the meaningfulness of biomarkers, while
      at the same time supporting and encouraging further research in this field.

PMID- 21088969
TI  - [Diagnostic spectrum, treatment indication and symptom duration in initial
      referrals to the rheumatologist].
AB  - There is evidence that early initiation of therapy in inflammatory rheumatic
      diseases, in particular rheumatoid arthritis (RA), has a positive effect on
      disease course.To investigate referral procedures, 198 German rheumatologists
      reported over a 3-month period and for each patient seen for the first time on:
      patient characteristics, specialization of the referring physician, symptom
      duration, time interval between making the appointment and the first visit,
      diagnoses and relevant drug history. Multivariate logistic regression analyses
      were performed to investigate the odds ratios for a first consultation within 3
      months after symptom onset.The 17,908 newly referred adult patients were 54 years
      old on average and 72% were women. Inflammatory rheumatic disease was diagnosed
      in 53%. Mean disease duration was 30 +/- 57 months (median 7.3 months). There was
      no apparent association between patient age, education, disease severity or
      specialisation of the referring physician; however, there was a clear association
      with waiting times to first consultation.A higher number of early arthritis
      clinics could significantly shorten the time to first rheumatological
      consultation. Therefore, more efforts need to be made to fast-track referrals
      from primary care physicians to rheumatologists as well as to optimise
      rheumatologists' appointment regulations for new patients. However, these efforts
      can only succeed with a significant increase in the number of rheumatologists,
      while ensuring a firm economic basis.

PMID- 21088970
TI  - [S 116b SGB V (social insurance code, book five) for rheumatology patients. An
      empirical assessment on the basis of administrative data].
AB  - BACKGROUND: The choice between outpatient and inpatient care is currently
      undergoing major changes within the German health care system with the amendment
      of S 116b SGB V. This study investigates what proportion of hitherto inpatient
      rheumatologic care could potentially be given on an outpatient basis. METHODS:
      The analysis is based on administrative inpatient data from 2004 to 2008 covering
      approximately 23.6 million private health insurance insurants. The selection of
      patients with rheumatological diseases was based on diagnosis according to ICD-10
      of S 116b SGB V. RESULTS: From 2004 to 2008 the number of all rheumatologic cases
      increased by 13.9%, while the average length of hospital stay decreased from 9.46
      days to 8.08 days and the number of attending hospitals declined by 3.1%. The
      number of rheumatologic cases with a short inpatient stay (<=2 days) increased by
      32.3%. We define the ambulatory potential as the proportion of patients with a
      short length of stay to the total of inpatient rheumatologic cases; this
      increased from 25.7% to 29.9%. DISCUSSION: Not all patients with a short
      inpatient stay can be transferred problem-free to ambulatory care. No channeling
      of patients to specialized centres has taken place thus far in Germany. Quality
      of care at the hospitals studied has not been considered. Further data are needed
      to link administrative data with quality care data.

PMID- 21088971
TI  - GSR deposition along the bullet path in contact shots to composite models.
AB  - In contact shots, all the materials emerging from the muzzle (combustion gases,
      soot, powder grains, and metals from the primer) will be driven into the depth of
      the entrance wound and the following sections of the bullet track. The so-called
      "pocket" ("powder cavity") under the skin containing soot and gunpowder particles
      is regarded as a significant indicator of a contact entrance wound since one
      would expect that the quantity of GSR deposited along the bullet's path rapidly
      declines towards the exit hole. Nevertheless, experience has shown that soot,
      powder particles, and carboxyhemoglobin may be found not only in the initial part
      of the wound channel, but also far away from the entrance and even at the exit.
      In order to investigate the propagation of GSRs under standardized conditions,
      contact test shots were fired against composite models of pig skin and 25-cm-long
      gelatin blocks using 9-mm Luger pistol cartridges with two different primers
      (Sinoxid(r) and Sintox(r)). Subsequently, 1-cm-thick layers of the gelatin blocks
      were examined as to their primer element contents (lead, barium, and antimony as
      discharge residues of Sinoxid(r) as well as zinc and titanium from Sintox(r)) by
      means of X-ray fluorescence spectroscopy. As expected, the highest element
      concentrations were found in the initial parts of the bullet tracks, but also the
      distal sections contained detectable amounts of the respective primer elements.
      The same was true for amorphous soot and unburned/partly burned powder particles,
      which could be demonstrated even at the exit site. With the help of a high-speed
      motion camera it was shown that for a short time the temporary cavitation extends
      from the entrance to the exit thus facilitating the unlimited spread of discharge
      residues along the whole bullet path.

PMID- 21088972
TI  - No effect of menstrual cycle phase on fuel oxidation during exercise in rowers.
AB  - The aim of this investigation was to examine the effects of menstrual cycle phase
      on substrate oxidation and lactate concentration during exercise. Eleven
      eumenorrheic female rowers (18.4 +/- 1.9 years; 172.0 +/- 4.0 cm; 67.2 +/- 8.4
      kg; 27.7 +/- 4.8% body fat) completed 1 h rowing ergometer exercise at 70% of
      maximal oxygen consumption (VO(2max)) during two different phases of the
      menstrual cycle: the follicular phase (FP) and the luteal phase (LP). Resting and
      exercise measurements of the whole body energy expenditure, oxygen consumption
      (VO(2)), respiratory exchange ratio (RER), substrate oxidation and lactate blood
      levels were made. Energy expenditure, VO(2) and heart rate during the 1-h
      exercise were not significantly different (P > 0.05) among menstrual cycle
      phases. Resting RER and RER during the entire 1 h exercise period were not
      significantly different among menstrual cycle phases. There was an increase (P <
      0.05) in RER in the transition between rest and exercise and a further increase
      in RER occurred after the first 30 min of exercise at both menstrual cycle
      phases. Blood lactate concentrations significantly increased in the transition
      between rest and exercise and remained relatively constant during the whole 1 h
      of exercise in both menstrual cycle phases. No menstrual cycle phase effect (P >
      0.05) was observed for blood lactate concentrations. In conclusion, our results
      demonstrated no effect of menstrual cycle phase on substrate oxidation and blood
      lactate concentration during rowing exercise at 70% of VO(2max) in athletes.
      Normally menstruating female rowers should not be concerned about their menstrual
      cycle phase with regard to substrate oxidation in everyday training.

PMID- 21088973
TI  - Effects of mode and intensity on the acute exercise-induced IL-6 and CRP
      responses in a sedentary, overweight population.
AB  - This study sought to compare the respective effects of resistance or aerobic
      exercise of higher or lower intensities on the acute plasma interleukin-6 (IL-6)
      and C-reactive protein (CRP) response in a sedentary, middle-aged, disease-free
      cohort. Following baseline testing, and in a randomized cross-over design, 12
      sedentary males completed four exercise protocols, including 40 min of moderate
      vigorous (M-VA) or low-intensity (LA) aerobic exercise on a cycle ergometer; and
      a moderate-vigorous (M-VR) or low-intensity (LR) full-body resistance session
      matched for protocol duration. Venous blood was obtained pre-, post-, 3 h post
      and 24 h post-exercise and analysed for IL-6, CRP, leukocyte count, myoglobin,
      creatine kinase (CK), and cortisol. Diet and physical activity were standardized
      24 h before and after exercise. Results indicated an elevated CRP response in the
      M-VR protocol in comparison to the low-intensity protocols (P < 0.05); however,
      no changes were evident between the moderate-vigorous intensity protocols. The
      moderate-vigorous intensity protocols induced significant increases of IL-6,
      cortisol, and leukocytes in comparison to the low-intensity protocols (P < 0.05).
      However, the IL-6 response showed no significant differences between the moderate
      vigorous intensity protocols, despite the M-VR protocol inducing the largest
      response of markers indicative of muscle damage (CK, myoglobin, and neutrophil
      count) (P < 0.05). Hence, indicating a disassociation between the IL-6 response
      and markers of muscle damage within the respective exercise bouts. The highest IL
      6 response was evident in the moderate-vigorous intensity protocols immediately
      post-exercise. Moreover, the exercise modality did not seem to influence the
      acute IL-6 and CRP response, with the main determinant of the IL-6 response being
      exercise intensity.

PMID- 21088976
TI  - Horner syndrome following thyroidectomy.

PMID- 21088975
TI  - Cystatin C, cardiometabolic risk, and body composition in severely obese
      children.
AB  - The aim of this study was to assess the relationship between cystatin C (CysC),
      cardiometabolic risk factors (CMRFs), and body composition in severely obese
      children. We evaluated 117 children aged 7-14 years old. Seventy-nine of these
      were severely obese (body mass index z-score ranging from 2.1 to 8.4), and 38
      were children with normal nutrition state. CysC was determined by
      immunonephelometry. CMRFs (glucose, insulin, high-density lipoprotein
      cholesterol, triglycerides, homocysteine, uric acid, alanine aminotransferase,
      and high-sensitivity C-reactive protein) were measured by standard biochemical
      methods. Blood pressure was evaluated at the clinical examination. Renal function
      was estimated using the glomerular filtration rate (eGFR) based upon creatinine
      levels, and body weight (Leger formula). Body composition was assessed by
      segmental bioelectrical impedance. Obese children at the highest tertile of CysC
      values were characterized by their aggregation of CMRFs. CysC concentration was
      associated with insulin resistance, alanine aminotransferase, uric acid, and
      homocysteine after adjusting for age, gender, and eGFR. CysC values were also
      correlated with the fat-free mass and specifically with skeletal muscle mass.
      CysC levels were correlated with CMRFs factors independently of renal function,
      and affected by skeletal muscle mass in severely obese children, although they
      are less influenced by this than is creatinine.

PMID- 21088974
TI  - Intestinal ischemia/reperfusion: microcirculatory pathology and functional
      consequences.
AB  - BACKGROUND: Intestinal ischemia and reperfusion (I/R) is a challenging and life
      threatening clinical problem with diverse causes. The delay in diagnosis and
      treatment contributes to the continued high in-hospital mortality rate. RESULTS:
      Experimental research during the last decades could demonstrate that
      microcirculatory dysfunctions are determinants for the manifestation and
      propagation of intestinal I/R injury. Key features are nutritive perfusion
      failure, inflammatory cell response, mediator surge and breakdown of the
      epithelial barrier function with bacterial translocation, and development of a
      systemic inflammatory response. This review provides novel insight into the basic
      mechanisms of damaged intestinal microcirculation and covers therapeutic targets
      to attenuate intestinal I/R injury. CONCLUSION: The opportunity now exists to
      apply this insight into the translation of experimental data to clinical trial
      based research. Understanding the basic events triggered by intestinal I/R may
      offer new diagnostic and therapeutic options in order to achieve improved outcome
      of patients with intestinal I/R injury.

PMID- 21088977
TI  - Nocturnal frontal lobe epilepsy presenting with restless leg syndrome-like
      symptoms.
AB  - We describe the case of a 22-year-old male affected by NFLE reporting paroxysmal
      RLS-like symptoms. The patient was referred to our Sleep Center due to nocturnal
      paresthesias and cramps involving the left leg and leading to sleep
      fragmentation. At age 4, the patient presented with secondary generalized
      seizures preceded by left leg discomfort, controlled on CBZ. After successive
      therapy discontinuation, leg symptoms built up in frequency and duration until a
      secondary generalized seizure re-occurred. On CBZ prompt resumption no further GM
      seizures occurred albeit persistence of night-time frequent cramps and
      paraesthesia. Sleep EEG demonstrated asymmetric interictal sharp theta on the
      right posterior frontal areas, whereas brain MRI results were consistent with a
      Taylor type right frontal cortical dysplasia. CBZ augmentation and add on therapy
      with LEV led to further frequency reduction of sensory symptoms.

PMID- 21088978
TI  - Accuracy of pre-surgical fMRI confirmed by subsequent crossed aphasia.
AB  - Atypical patterns of language activation in functional MRI (fMRI) are not
      unusual, particularly in patients with severe epilepsy. Still, the functional
      significance of these activations is under debate. We describe a case of a right
      handed patient affected by drug-refractory right temporal lobe epilepsy in whom
      pre-surgical fMRI showed bilateral language activations, greater in the right
      hemisphere (RH). After surgery, a right subdural hematoma caused epileptic status
      and severe aphasia. This post-surgical complication of a crossed aphasia
      confirmed the prior fMRI findings of RH language thus stressing the value of pre
      surgical fMRI evaluations, even when surgery is planned in the RH of a right
      handed patient.

PMID- 21088979
TI  - Recovery and phylogenetic diversity of culturable fungi associated with marine
      sponges Clathrina luteoculcitella and Holoxea sp. in the South China Sea.
AB  - Sponge-associated fungi represent an important source of marine natural products,
      but little is known about the fungal diversity and the relationship of sponge
      fungal association, especially no research on the fungal diversity in the South
      China Sea sponge has been reported. In this study, a total of 111 cultivable
      fungi strains were isolated from two South China Sea sponges Clathrina
      luteoculcitella and Holoxea sp. using eight different media. Thirty-two
      independent representatives were selected for analysis of phylogenetic diversity
      according to ARDRA and morphological characteristics. The culturable fungal
      communities consisted of at least 17 genera within ten taxonomic orders of two
      phyla (nine orders of the phylum Ascomycota and one order of the phylum
      Basidiomycota) including some potential novel marine fungi. Particularly, eight
      genera of Apiospora, Botryosphaeria, Davidiella, Didymocrea, Lentomitella,
      Marasmius, Pestalotiopsis, and Rhizomucor were isolated from sponge for the first
      time. Sponge C. luteoculcitella has greater culturable fungal diversity than
      sponge Holoxea sp. Five genera of Aspergillus, Davidiella, Fusarium,
      Paecilomyces, and Penicillium were isolated from both sponges, while 12 genera of
      Apiospora, Botryosphaeria, Candida, Marasmius, Cladosporium, Didymocrea,
      Hypocrea, Lentomitella, Nigrospora, Pestalotiopsis, Rhizomucor, and
      Scopulariopsis were isolated from sponge C. luteoculcitella only. Order
      Eurotiales especially genera Penicillium, Aspergillus, and order Hypocreales
      represented the dominant culturable fungi in these two South China Sea sponges.
      Nigrospora oryzae strain PF18 isolated from sponge C. luteoculcitella showed a
      strong and broad spectrum antimicrobial activities suggesting the potential for
      antimicrobial compounds production.

PMID- 21088980
TI  - Construction and characterization of the BAC library for common carp Cyprinus
      carpio L. and establishment of microsynteny with zebrafish Danio rerio.
AB  - A bacterial artificial chromosome (BAC) library of common carp Cyprinus carpio L.
      was constructed as a part of ongoing common carp genome project, which is aiming
      assembly of common carp genome. The library, containing a total of 92,160 BAC
      clones with an average insert size of 141 kb, was constructed into the
      restriction site of Hind III on BAC vector CopyControl pCC1BAC, covering 7.7 X
      haploid genome equivalents. Three dimension pools and superpools of the BAC
      library were established and 23 positive clones of 14 targets were identified
      from one-fifth of the BAC library. Pilot project of BAC end sequencing was
      conducted on 2,688 BAC ends from 1,344 clones and harvested 2,522 high-quality
      Q20 sequences with average length of 677 bp. The sequencing success rate was
      93.8% and pair-end success rate was 92.3%. A total of 212 microsyntenies had been
      established between common carp and zebrafish genomes as a trial for genome-wide
      comparative genomics in these two closely related species.

PMID- 21088981
TI  - HLA-G: a look back, a look forward.

PMID- 21088982
TI  - Theoretical studies on the interaction of partial agonists with the 5-HT2A
      receptor.
AB  - A series of 51 5-HT(2A) partial agonistic arylethylamines (primary or
      benzylamines) from different structural classes (indoles, methoxybenzenes,
      quinazolinediones) was investigated by fragment regression analysis (FRA),
      docking and 3D-QSAR approaches. The data, pEC(50) values and intrinsic activities
      (E(max)) on rat arteries, show high variability of pEC(50) from 4 to 10 and of
      E(max) from 15 to 70%. FRA indicates which substructures affect potency or
      intrinsic activity. The high contribution of halogens in para position of
      phenethylamines to pEC(50) points to a specific hydrophobic pocket. Other results
      suggest the significance of hydrogen bonds of the aryl moiety for activation and
      the contrary effect of benzyl groups on affinity (increasing) and intrinsic
      activity (decreasing). Results from fragment regression and data on all available
      mutants were considered to derive a common binding site at the rat 5-HT(2A)
      receptor. After generation and MD simulations of a receptor model based on the
      beta(2)-adrenoceptor structure, typical derivatives were docked, leading to the
      suggestion of common interactions, e.g., with serines in TM3 and TM5 and with a
      cluster of aromatic amino acids in TM5 and TM6. The whole series was aligned by
      docking and minimization of the complexes. The pEC(50) values correlate well with
      Sybyl docking energies and hydrophobicity of the aryl moieties. With this
      alignment, CoMFA and CoMSIA approaches based on a training set of 36 and a test
      set of 15 compounds were performed. The correlation of pEC(50) with steric,
      electrostatic, hydrophobic and H-bond acceptor fields resulted in sufficient fit
      (q (2): 0.75-0.8, r (2): 0.92-0.95) and predictive power (r (pred) (2) : 0.85
      0.88). The important interaction regions largely reflect the patterns provided by
      the putative binding site. In particular, the fit of the aryl moieties and benzyl
      substituents to two hydrophobic pockets is evident.

PMID- 21088983
TI  - A case of resistance to clopidogrel and prasugrel after percutaneous coronary
      angioplasty.

PMID- 21088984
TI  - A novel shell-structure cell microcarrier (SSCM) for cell transplantation and
      bone regeneration medicine.
AB  - PURPOSE: The present study aims to develop a novel open and hollow shell
      structure cell microcarrier (SSCM) to improve the anchorage-dependent cell (ADC)
      loading efficiency, increase the space for cell proliferation and tissue
      regeneration, and better propel its therapeutic effects. METHODS: Gelatin
      particles were prepared with oil/water/oil (o/w/o) technique and modified by an
      adjustable surface crosslinking technique and subsequent release of uncrosslinked
      material. Optical microscopy and scanning electron microscopy (SEM) were utilized
      to observe the morphologies of the microcarriers. Cell loading tests were
      performed to evaluate the biocompatibilities and effect on osteogenesis of SSCM.
      RESULTS: SSCMs were successfully fabricated via the surface technique. The shell
      structure could allow the cell to attach and grow on both outer and inner surface
      of sphere and provide adequate space for cell proliferation and extracellular
      matrix (ECM) secretion. The cell loading rate, proliferation rate and
      osteogenesis-related gene expressions on the SSCMs were higher than those on the
      spherical gelatin microcarriers. CONCLUSIONS: The outstanding performance of
      injectable SSCMs endowed with favorable micro-structure, desirable
      cytocompatibility and enhanced cell affinity makes them as a good choice as cell
      delivery vehicle for transplanting therapeutic cells towards the scope of tissue
      regeneration.

PMID- 21088985
TI  - Bioactive electrospun scaffolds delivering growth factors and genes for tissue
      engineering applications.
AB  - A biomaterial scaffold is one of the key factors for successful tissue
      engineering. In recent years, an increasing tendency has been observed toward the
      combination of scaffolds and biomolecules, e.g. growth factors and therapeutic
      genes, to achieve bioactive scaffolds, which not only provide physical support
      but also express biological signals to modulate tissue regeneration. Huge efforts
      have been made on the exploration of strategies to prepare bioactive scaffolds.
      Within the past five years, electrospun scaffolds have gained an exponentially
      increasing popularity in this area because of their ultrathin fiber diameter and
      large surface-volume ratio, which is favored for biomolecule delivery. This paper
      reviews current techniques that can be used to prepare bioactive electrospun
      scaffolds, including physical adsorption, blend electrospinning, coaxial
      electrospinning, and covalent immobilization. In addition, this paper also
      analyzes the existing challenges (i.e., protein instability, low gene
      transfection efficiency, and difficulties in accurate kinetics prediction) to
      achieve biomolecule release from electrospun scaffolds, which necessitate further
      research to fully exploit the biomedical applications of these bioactive
      scaffolds.

PMID- 21088986
TI  - Progress towards a needle-free hepatitis B vaccine.
AB  - Hepatitis B virus (HBV) infection is a worldwide public health problem.
      Vaccination is the most efficient way to prevent hepatitis B. Despite the success
      of the currently available vaccine, there is a clear need for the development of
      new generation of HBV vaccines. Needle-free immunization is an attractive
      approach for mass immunization campaigns, since avoiding the use of needles
      reduces the risk of needle-borne diseases and prevents needle-stick injuries and
      pain, thus augmenting patient compliance and eliminating the need for trained
      medical personnel. Moreover, this kind of immunization was shown to induce good
      systemic as well as mucosal immunological responses, which is important for the
      creation of both a prophylactic and therapeutic vaccine. In order to produce a
      better, safer, more efficient and more suitable vaccine, adjuvants have been
      used. In this article, several adjuvants tested over the years for their
      potential to help create a needle-free vaccine against HBV are reviewed.

PMID- 21088987
TI  - Childbearing, stress and obesity disparities in women: a public health
      perspective.
AB  - The perinatal period, from early in the first trimester to 1 year postpartum,
      provides opportunities for novel public health interventions to reduce obesity
      disparities. We present a unifying socio-biological framework to suggest
      opportunities for multidisciplinary research and public health approaches to
      elucidate and target the mechanisms for the development of maternal obesity and
      related disparities. The framework illustrates the interplay of the social,
      cultural and physical environment; stress appraisal and response; and coping
      behaviors on short-term outcomes (e.g. allostatic load and gestational weight
      gain), the intermediate outcomes of persistent insulin resistance and post-partum
      weight retention, and longer term outcomes of obesity and its disease
      consequences. Testing the proposed relationships may provide insights into how
      childbearing risk factors such as gestational weight gain, postpartum weight
      retention and parity contribute to obesity, which are needed to inform public
      health policies and clinical care guidelines aimed at reducing obesity and
      improving the health of women.

PMID- 21088988
TI  - A review of prenatal group care literature: the need for a structured theoretical
      framework and systematic evaluation.
AB  - The purpose of this article is to systematically review the literature on group
      based prenatal care related to patient participation, attendance, satisfaction,
      knowledge, pregnancy and birth outcomes, and program cost. MEDLINE, CINAHL, and
      PsycINFO sources were searched for English-language articles published any time
      prior to June 2010. Manual searches of bibliographies were conducted and experts
      were consulted to identify possible sources. Descriptive, cross-sectional,
      cohort, and randomized control studies that assessed group-based prenatal care
      were selected. Of the 15 articles reviewed, 11 studies met inclusion criteria for
      analysis of the study attributes and outcome data related to patient
      participation, attendance, satisfaction, knowledge, as well as breastfeeding,
      pregnancy and birth outcomes, and program cost. Results from the review show that
      group prenatal care may be associated with improved patient and birth outcomes
      including reduction in the number of preterm deliveries, higher patient
      participation and satisfaction, and increased initiation of breastfeeding.
      Prenatal group care research is limited by relatively few studies, most of which
      lack rigor. The current model of prenatal group care lacks a theoretical
      framework for describing and evaluating group processes as well as intermediary
      factors of prenatal and birth outcomes. Research on group care would benefit from
      additional randomized controlled trials that assess cost and sustainability and
      formally evaluate group process and intermediary factors thought to account for
      improved outcomes.

PMID- 21088989
TI  - HIV interventions to reduce HIV/AIDS stigma: a systematic review.
AB  - We reviewed the literature to determine the effectiveness of HIV-related
      interventions in reducing HIV/AIDS stigma. Studies selected had randomized
      controlled trial (RCT), pretest-posttest with a non-randomized control group, or
      pretest-posttest one group study designs in which HIV-related interventions were
      being evaluated, and in which HIV/AIDS stigma was one of the outcomes being
      measured. A checklist was used to extract data from accepted studies, assess
      their internal validity, and overall quality. Data were extracted from 19
      studies, and 14 of these studies demonstrated effectiveness in reducing HIV/AIDS
      stigma. Only 2 of these 14 effective studies were considered good studies, based
      on quality, the extent to which the intervention focused on reducing HIV/AIDS
      stigma, and the statistics reported to demonstrate effectiveness. Future studies
      to reduce HIV/AIDS stigma could improve by designing interventions that pay
      greater attention to internal validity, use validated HIV/AIDS stigma
      instruments, and achieve both statistical and public health significance.

PMID- 21088990
TI  - "For most of us Africans, we don't just speak": a qualitative investigation into
      collaborative heterogeneous PBL group learning.
AB  - Collaborative approaches such as Problem Based Learning (PBL) may provide the
      opportunity to bring together diverse students but their efficacy in practice and
      the complications that arise due to the mixed ethnicity needs further
      investigation. This study explores the key advantages and problems of
      heterogeneous PBL groups from the students' and teachers' opinions. Focus groups
      were conducted with a stratified sample of second year medical students and their
      PBL teachers. We found that students working in heterogeneous groupings interact
      with students with whom they don't normally interact with, learn a lot more from
      each other because of their differences in language and academic preparedness and
      become better prepared for their future professions in multicultural societies.
      On the other hand we found students segregating in the tutorials along racial
      lines and that status factors disempowered students and subsequently their
      productivity. Among the challenges was also that academic and language diversity
      hindered student learning. In light of these the recommendations were that
      teachers need special diversity training to deal with heterogeneous groups and
      the tensions that arise. Attention should be given to create 'the right mix' for
      group learning in diverse student populations. The findings demonstrate that
      collaborative heterogeneous learning has two sides that need to be balanced. On
      the positive end we have the 'ideology' behind mixing diverse students and on the
      negative the 'practice' behind mixing students. More research is needed to
      explore these variations and their efficacy in more detail.

PMID- 21088991
TI  - Improving the working relationship between doctors and pharmacists: is inter
      professional education the answer?
AB  - Despite their common history, there are many cultural, attitudinal and practical
      differences between the professions of medicine and pharmacy that ultimately
      influence patient care and health outcomes. While poor communication between
      doctors and pharmacists is a major cause of medical errors, it is clear that
      effective, deliberate doctor-pharmacist collaboration within certain clinical
      settings significantly improves patient care. This may be particularly true for
      those patients with chronic illnesses and/or requiring regular medication
      reviews. Moreover, in hospitals, clinical and antibiotic pharmacists are
      successfully influencing prescribing and infection control policy. Under the new
      Irish Pharmacy Act (2007), pharmacists are legally obliged to provide
      pharmaceutical care to their patients, thus fulfilling a more patient-centred
      role than their traditional 'dispensing' one. However, meeting this obligation
      relies on the existence of good doctor-pharmacist working relationships, such
      that inter-disciplinary teamwork in monitoring patients becomes the norm in all
      healthcare settings. As discussed here, efforts to improve these relationships
      must focus on the strategic introduction of agreed changes in working practices
      between the two professions and on educational aspects of pharmaceutical care.
      For example, standardized education of doctors/medical students such that they
      learn to prescribe in an optimal manner and ongoing inter-professional education
      of doctors and pharmacists in therapeutics, are likely to be of paramount
      importance. Here, insights into the types of factors that help or hinder the
      improvement of these working relationships and the importance of education and
      agreed working practices in defining the separate but inter-dependent professions
      of pharmacy and medicine are reviewed and discussed.

PMID- 21088992
TI  - Safety of adenosine pharmacologic stress myocardial perfusion imaging in
      orthotopic cardiac transplant recipients: a single center experience of 102
      transplant patients.
AB  - Denervation super-sensitivity to adenosine is well described in cardiac
      transplant (CT) patients particularly early after transplant. The safety and
      hemodynamic effects of adenosine SPECT (A-SPECT) has not been described in a
      large series of CT patients. Single center retrospective study of 102 CT patients
      undergoing A-SPECT were compared to an age-gender matched patients in a 2:1
      fashion who underwent A-SPECT in the same time period. Multivariate logistic
      regression model were used to identify independent predictors of advanced AV
      block. The average time from CT to A-SPECT was 8.5 +/- 4.5 years. Average age was
      57 years with 80% males. In comparison to the control group, adenosine infusion
      was associated with a higher incidence of sinus pause (4.9% vs. 0%), 2nd (11.8%
      vs. 4.9%) and 3rd degree AVB (2.9% vs. 0%) in CT patients (all P < 0.05). Prior
      use of aspirin and baseline 1st degree AVB were significant independent
      predictors of adenosine induced AVB. Baseline right or left bundle branch block,
      beta-blockers, calcium blockers or digoxin were not associated with occurrence of
      AVB. Only 1.9% of A-SPECT studies were terminated due to bradyarrythmia with 1
      patient requiring aminophylline. There were no significant immediate or long term
      adverse events in these patients. Adenosine pharmacologic stress is associated
      with a higher incidence of AVB and sinus pause in CT patients reflecting
      persistence of super sensitivity late after CT. Nevertheless these
      bradyarrythmias are transient without any sequelae suggesting that A-SPECT can be
      performed safely in CT patients.

PMID- 21088993
TI  - Head-to-head comparison of first-pass MR perfusion imaging during adenosine and
      high-dose dobutamine/atropine stress.
AB  - To directly compare the stressor capabilities of adenosine and high-dose
      dobutamine/atropine using first pass myocardial perfusion magnetic resonance
      imaging. Fourty-one patients with suspected or known coronary artery disease
      underwent cardiac magnetic resonance (CMR) perfusion imaging at 1.5 Tesla on two
      consecutive days prior to invasive coronary angiography. On day 1 a standard CMR
      perfusion protocol during adenosine stress was carried out (adenosine infusion
      with 140 MUg/kg/min, 0.1 mmol/kg Gd-DTPA). On day 2, the identical CMR perfusion
      sequence was repeated during a standard high-dose dobutamine/atropine stress
      protocol at rest and during target heart rate (85% of maximum age-predicted heart
      rate). Stress-inducible perfusion deficits were evaluated visually regarding
      presence and transmural extent. Quantitative coronary angiography served as the
      reference standard with significant stenosis defined as >=50% luminal diameter
      reduction. Twenty-five patients (61%) had significant coronary stenoses.
      Adenosine and dobutamine stress CMR perfusion imaging resulted in an equally high
      sensitivity and specificity for the stenosis detection on a per patient basis (92
      and 75% for both stressors, respectively). Agreement of both stressors with
      regard to the presence or absence of stress-inducible perfusion deficits was
      nearly perfect using patient- and segment based analysis (kappa 1.0 and 0.92,
      respectively). Adenosine and dobutamine/atropine stress CMR perfusion imaging are
      equally capable to identify stress inducible deficits and resulted in an almost
      identical extent of ischemic reactions. Though adenosine stress CMR perfusion
      imaging is widely employed, dobutamine stress CMR perfusion represents a valid
      alternative and may be particularly useful in patients with contraindications to
      vasodilator testing.

PMID- 21088995
TI  - Law of the Minimum paradoxes.
AB  - The "Law of the Minimum" states that growth is controlled by the scarcest
      resource (limiting factor). This concept was originally applied to plant or crop
      growth (Justus von Liebig, 1840, Salisbury, Plant physiology, 4th edn.,
      Wadsworth, Belmont, 1992) and quantitatively supported by many experiments. Some
      generalizations based on more complicated "dose-response" curves were proposed.
      Violations of this law in natural and experimental ecosystems were also reported.
      We study models of adaptation in ensembles of similar organisms under load of
      environmental factors and prove that violation of Liebig's law follows from
      adaptation effects. If the fitness of an organism in a fixed environment
      satisfies the Law of the Minimum then adaptation equalizes the pressure of
      essential factors and, therefore, acts against the Liebig's law. This is the the
      Law of the Minimum paradox: if for a randomly chosen pair "organism-environment"
      the Law of the Minimum typically holds, then in a well-adapted system, we have to
      expect violations of this law.For the opposite interaction of factors (a
      synergistic system of factors which amplify each other), adaptation leads from
      factor equivalence to limitations by a smaller number of factors.For analysis of
      adaptation, we develop a system of models based on Selye's idea of the universal
      adaptation resource (adaptation energy). These models predict that under the load
      of an environmental factor a population separates into two groups (phases): a
      less correlated, well adapted group and a highly correlated group with a larger
      variance of attributes, which experiences problems with adaptation. Some
      empirical data are presented and evidences of interdisciplinary applications to
      econometrics are discussed.

PMID- 21088994
TI  - In vitro hepatoprotective and antioxidant activities of crude extract and
      isolated compounds from Ficus gnaphalocarpa.
AB  - The in vitro hepatoprotective effect of the methanolic extract from Ficus
      gnaphalocarpa (Miq.) Steud. ex A. Rich (Moraceae) on the CCl4-induced liver cell
      damage as well as the possible antioxidant mechanisms involved in this protective
      effect, were investigated. The phytochemical investigation of this methanolic
      extract led to the isolation of six compounds identified as: betulinic acid (1);
      3-methoxyquercetin (2); catechin (3); epicatechin (4); quercetin (5); and
      quercitrin (6). The hepatoprotective activity of these compounds was tested in
      vitro against CCl4-induced damage in rat hepatoma cells. In addition, radical
      scavenging activity, beta-carotene-linoleic acid model system, ferric-reducing
      antioxidant parameter and microsomal lipid peroxidation assays were used to
      measure antioxidant activity of crude extract and isolated compounds. Silymarin
      and trolox were used as standard references and, respectively, exhibited
      significant hepatoprotective and antioxidant activities. (5), (6) and (2) showed
      significant antioxidant and hepatoprotective activities as indicated by their
      ability to prevent liver cell death and lactate dehydrogenase leakage during CCl4
      intoxication. These results suggest that the protective effects of crude extract
      of F. gnaphalocarpa against the CCl4-induced hepatotoxicity possibly involve the
      antioxidant effect of these compounds.

PMID- 21088997
TI  - The equilibrium of phosphatidylcholine-amino acid system in monolayer at the
      air/water interface.
AB  - Monolayers of phosphatidylcholine, tyrosine, and phenylalanine and binary
      mixtures phosphatidylcholine-tyrosine or phosphatidylcholine-phenylalanine were
      investigated at the air/water interface. Phosphatidylcholine (lecithin, PC),
      tyrosine (Tyr), and phenylalanine (Phe) were used in the experiment. The surface
      tension values of pure and mixed monolayers were used to calculate pi-A
      isotherms. The surface tension measurements were carried out at 22 degrees C
      using an improved Teflon trough and a Nima 9000 tensiometer. The Teflon trough
      was filled with a subphase of triple-distilled water. Known amounts of lipid
      dissolved in 1-chloropropane were placed at the surface using a syringe. The
      interactions between lecithin and amino acid result in significant deviations
      from the additivity rule. An equilibrium theory to describe the behavior of
      monolayer components at the air/water interface was developed in order to obtain
      the stability constants of PC-Tyr as well as PC-Phe complexes. We considered the
      equilibrium between the individual components and the complex and established
      that lecithin and amino acid formed highly stable 1:1 complex.

PMID- 21088996
TI  - Knockdown of microRNA-21 inhibits proliferation and increases cell death by
      targeting programmed cell death 4 (PDCD4) in pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: This study aims to examine the expression of a panel of five microRNAs
      (miRNA) in pancreatic ductal adenocarcinoma (PDAC) and the functional effect of
      miR-21 inhibition in PDAC cell lines. BACKGROUND: miRNA are short, non-coding RNA
      molecules, which play important roles in several cellular processes by silencing
      expression of their target genes through translational repression or mRNA
      degradation. They are often aberrantly expressed in cancer, and this
      dysregulation can promote carcinogenesis by altering the expression of tumour
      suppressor or oncogenes. METHODS: miRNA expression levels were measured in 24
      PDAC tumour/matched adjacent normal tissue samples and three PDAC cell lines
      using reverse transcription polymerase chain reaction. Levels of cell
      proliferation and death and expression of programmed cell death 4 (PDCD4; tumour
      suppressor) were studied in PDAC cells (MIA-Pa-Ca-2) in the absence or presence
      of a miR-21 inhibitor. RESULTS: PDAC primary tissues and cell lines displayed a
      consistent upregulation of miR-21 (P < 0.0001) and downregulation of both miR
      148a (P < 0.0001) and miR-375 (P < 0.0001) relative to adjacent normal tissue.
      Furthermore, miR-21 levels in the primary tumours correlated with disease stage
      (P < 0.0001). Inhibition of miR-21 in MIA-Pa-Ca-2 PDAC cells led to reduced cell
      proliferation (P < 0.01) and increased cell death (P < 0.01), with simultaneous
      increase in levels of the tumour suppressor, PDCD4 (P < 0.01). CONCLUSION: miRNA
      expression profiles may be used as biomarkers for detecting pancreatic cancer.
      Moreover, miR-21 could be a predictor of disease progression and a possible
      therapeutic target in part by upregulating PDCD4 in pancreatic cancer.

PMID- 21088998
TI  - Encapsulated malignant follicular cell-derived thyroid tumors.
AB  - Encapsulated malignant follicular cell-derived thyroid tumors are subject to
      considerable controversies. This group includes encapsulated follicular variant
      of papillary carcinoma (FVPTC) and encapsulated (so-called minimally invasive)
      follicular carcinoma (EFC). FVPTC usually presents as an encapsulated tumor and
      less commonly as a partially/nonencapsulated infiltrative neoplasm. The
      encapsulated form rarely metastasizes to lymph node, whereas infiltrative tumors
      often harbor nodal metastases. Encapsulated FVPTC have a molecular profile very
      close to follicular adenomas/carcinomas (high rate of RAS and absence of BRAF
      mutations). Infiltrative follicular variant has an opposite molecular profile
      closer to classical papillary thyroid carcinoma than to follicular
      adenoma/carcinoma (BRAF > RAS mutations). Noninvasive encapsulated FVPTC are
      extremely indolent even if treated with lobectomy without radioactive iodine
      therapy. Although most EFC are thought to have an excellent outcome, there are
      cases of EFC that recur and metastasize. EFC with angioinvasion, especially if
      extensive, have a significant rate of distant recurrence. Encapsulated FVPTC have
      a molecular profile and a clinical behavior very similar to the follicular
      adenoma/carcinoma class of tumor. If noninvasive, encapsulated FVPTC should be
      treated in a very conservative fashion. EFC with angioinvasion, especially if
      extensive, should not be termed minimally invasive in order to prevent
      undertreatment of the patient.

PMID- 21088999
TI  - Advances in alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) remains a leading cause of death from liver disease
      in the United States. In studies from the Veterans Administration, patients with
      cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality
      over a 4-year period, with most of those deaths occurring in the first month.
      Thus, the prognosis for this disease is more ominous than for many common types
      of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant
      economic burden from lost wages, health care costs, and lost productivity.
      Unfortunately, there is still no Food and Drug Administration-approved or widely
      accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a
      more detailed understanding of mechanisms of liver injury. This article reviews
      recent advances in mechanisms and therapy related to five major areas of direct
      relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling;
      malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also
      review why therapies related to these mechanisms have performed well in
      experimental animals and in vitro systems, but have not necessarily translated
      into effective therapy for humans with ALD.

PMID- 21089000
TI  - New insights into the biology and pathobiology of beta2-glycoprotein I.
AB  - beta2-glycoprotein I (beta2GPI) is the major autoantigen in the antiphospholipid
      syndrome. The central importance of understanding beta2GPI physiology from the
      perspective of the rheumatologist is that it forms the foundation for
      understanding the pathophysiology underlying autoantibody generation, and the
      diverse mechanisms by which anti-beta2GPI antibodies in complex with beta2GPI may
      predispose an individual to the antiphospholipid syndrome clinical phenotype.
      This review examines some of the latest novel findings in this area.

PMID- 21089001
TI  - Is a silastic radial head still a reasonable option?
AB  - BACKGROUND: The importance of the radial head to elbow function and stability is
      increasingly apparent. Although preservation of the native radial head is
      preferred, severely comminuted fractures may necessitate resection or
      arthroplasty. Silastic radial head arthroplasty has been condemned on the basis
      of several sporadic reports of silicone synovitis. However, problems of
      "overstuffing," cartilage wear, and motion loss are becoming apparent with metal
      prostheses, indicating this also is not an ideal solution. Thus, the choices
      remain controversial. QUESTIONS/PURPOSES: We asked whether intact or
      reconstructed primary elbow stabilizers permit use of silastic radial head
      implants without fragmentation, failure, and silicone synovitis. METHODS: We
      retrospectively reviewed 23 patients with unreconstructable radial head fractures
      who were treated with silastic radial head arthroplasty and concomitant repair
      and/or reconstruction of the medial ulnar collateral ligament and/or lateral
      ulnar collateral ligament. Analysis included range of motion, pain, stability,
      and radiographic assessments; Disabilities of the Arm, Shoulder, and Hand (DASH)
      questionnaire; and Mayo Elbow Performance Score (MEPS). The minimum followup was
      16 months (average, 69.6 months; range, 16-165 months). RESULTS: At last
      followup, the mean elbow flexion was 145 degrees , extension 11 degrees ,
      supination 80 degrees , and pronation 83 degrees . The mean MEPS score was 88.9.
      The mean DASH score was 11.8. There were eight reoperations, none resulting from
      failure of the radial head implants. CONCLUSIONS: These results demonstrate
      silastic radial heads can be used with low complication rates and without
      evidence of synovitis when concomitant elbow ligament repair or reconstruction is
      performed. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 21089002
TI  - Laminoplasty versus laminectomy and fusion for multilevel cervical spondylotic
      myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy is increasingly prevalent in the
      elderly and is the leading cause of spinal cord dysfunction in this population.
      Laminectomy with fusion and laminoplasty halt progression of myelopathy in these
      patients; however, both procedures have well-documented complications and
      associated morbidity and it is unclear which might be most advantageous.
      QUESTIONS/PURPOSES: We therefore compared the pain, function and alignment of
      patients who underwent laminectomy with fusion to those with laminoplasty for the
      treatment of multilevel cervical spondylotic myelopathy. METHODS: We performed a
      retrospective matched cohort analysis on all 121 patients from 2002 to 2007 who
      underwent laminectomy with fusion (82) or laminoplasty (39) for multilevel
      cervical spondylotic myelopathy. We determined change in preoperative and
      postoperative sagittal alignment using Cobb measurement, development of
      junctional stenosis, and subjective improvements in pain and gait. Complications
      were recorded for both cohorts. RESULTS: The majority of patients in both cohorts
      reported improvements in pain and gait postoperatively. There were seven
      complications in the laminectomy and fusion cohort (9%) with two patients
      requiring formal revision surgery (2%). There were five complications in the
      laminoplasty cohort (13%) with two formal revision procedures (5%). CONCLUSIONS:
      Patients in both the laminectomy with fusion and laminoplasty cohorts reported
      similar functional improvements after treatment for cervical spondylotic
      myelopathy. Prospective randomized control trials are needed to determine whether
      one procedure is truly superior. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 21089003
TI  - Are GSTM1, GSTT1 and CAG repeat length of androgen receptor gene polymorphisms
      associated with risk of prostate cancer in Iranian patients?
AB  - We conducted this study to investigate whether CAG repeat length in androgen
      receptor gene and GSTM1 and GSTT1 polymorphisms influence prostate cancer risk in
      Iranian newly diagnosed cancer patients compared to age-matched BPH group and
      healthy individuals. DNA from 110 pathologically-confirmed prostate cancer
      patients, 99 age-matched men with Benign Prostatic Hyperplasia (BPH) and 100
      healthy individuals were extracted and amplified by polymerase chain reaction
      (PCR). PCR products were examined by electrophoresis and sequencing. The mean
      number of CAG repeat in prostate cancer patients was significantly smaller than
      normal (19.9 vs 22.8; p < 0.0001) and BPH groups (19.9 vs 21.9; P < 0.0001) The
      mean difference between normal individuals and BPH group was also significant
      (21.9 vs. 22.8; P = 0.003). Presence of GSTM1 null genotype were significantly
      higher in cancer and BPH group vs. normal individuals (both P values < 0.0001).
      there was not seen association between GSTT1 null or positive genotype with
      cancer risk, but analysis of GSTM1 null and GSTT1 positive in combination was
      statistically associated with Prostate cancer risk (OR = 8.4, 95% CI 1.53-46.73).
      Our results showed that CAG repeat polymorphism in AR gene may act as a risk
      modifier and GSTM1 null genotypes also may be contributed to prostate cancer
      susceptibility in Iranian patients.

PMID- 21089004
TI  - Enzymatic polymer functionalisation: advances in laccase and peroxidase derived
      lignocellulose functional polymers.
AB  - Enzymatic polymer functionalisation has entered its most fascinating period with
      development in this field largely at the basic research level and pilot scale
      applications. Development of enzymatic processes for the development of
      lignocellulose-based functional polymers has not been spared, ranging from
      textile fibres with novel properties (antimicrobials properties, hydrophobic
      properties, attractive shed colours, etc.) to fibreboards. Enzymatic processes
      are also being actively pursued aimed at developing functional polymers from
      lignin (a major by product of the pulp and process).

PMID- 21089005
TI  - [Children of mentally ill parents: the impact of parental psychiatric diagnosis,
      comorbidity, severity and chronicity on the well-being of children].
AB  - OBJECTIVE: Children of mentally ill parents are known as a high-risk population
      for the development of psychological disturbances. In this study, the psychiatric
      diagnoses, the severity and chronicity and the comorbidity of a parental mental
      illness as well as the non-specific parameters were examined in terms of their
      influence on the children's mental health. METHODS: n = 62 children of
      psychiatric inpatients were examined regarding their psychic symptomatology,
      assessed with the CBCL-Parent Report Form. The psychiatric ICD-10 diagnoses and
      comorbidities as well as the severity (CGI) of the mentally ill parents were
      collected from psychiatric assessment forms. RESULTS: Children of parents with
      personality disorders (PD) are evaluated as highly affected by their parents,
      regardless of whether the PD is the primary or the comorbid diagnosis. Children
      of parents suffering from addictive disorders are seen as the least affected by
      their parents. Overall, children of parents with multiple diagnoses tend to be
      rated as more affected. Severity of illness and chronicity do not have a
      considerable impact on the children's development of mental health problems.
      Strikingly, children with a high length of exposure to a parental illness are
      psychologically less affected than children with shorter times of exposure. Thus,
      children possibly acquire effective coping mechanisms with increasing time of
      exposure. CONCLUSIONS: The results reveal the necessity of preventive programmes,
      especially in case of personality disorders. In addition the necessity for
      external assessment of the children becomes clear, especially in those cases
      where the parents exhibit a poor acceptance of their disease.

PMID- 21089006
TI  - Neonatal enteroviral sepsis/meningoencephalitis and hemophagocytic
      lymphohistiocytosis: diagnostic challenges.
AB  - We present the clinical course of three neonates with proven enteroviral
      infection and an initial clinical picture suggestive of hemophagocytic
      lymphohistiocytosis (HLH). After a complete workup, only one was treated for HLH.
      Of particular interest, the first newborn presented with hemophagocytic cells in
      the cerebrospinal fluid (CSF) and proved to have enteroviral meningoencephalitis
      but was ultimately not diagnosed with HLH. A fourth infant, who fulfilled the
      diagnostic criteria for HLH but did not have enteroviral infection, is included
      for comparison. We suggest that severe neonatal enteroviral infection and HLH are
      difficult to distinguish. Careful assessment is recommended, as prognosis and
      treatment differ between these two entities. Literature regarding neonatal
      enteroviral infection and HLH is reviewed, to demonstrate the continuum between
      the inflammation triggered by enteroviral infection and the occurrence of HLH, as
      well as their comparable CSF findings.

PMID- 21089007
TI  - Multifractal analysis of fetal heart rate variability in fetuses with and without
      severe acidosis during labor.
AB  - We performed multifractal analysis of fetal heart rate (FHR) variability in
      fetuses with and without acidosis during labor. Multifractal analysis was
      performed on fetal electrocardiograms in 10-minute sliding windows within the
      last 2 hours before delivery in 45 term fetuses divided in three groups according
      to umbilical arterial pH and FHR pattern: group A had pH >=7.30 and normal FHR,
      group B had pH >=7.30 and intermediate or abnormal FHR, and group C had acidosis
      (pH <=7.05) and intermediate or abnormal FHR. Six multifractal parameters were
      compared using Wilcoxon rank sum test. Multifractal parameters were significantly
      different between the three groups in the last 10 minutes before delivery (P
      <0.05). Two parameters (H(min), zeta(2)) exhibited a significant difference 70
      minutes before delivery, and one parameter (C(2)) was different 10 minutes before
      birth (P <0.05). Multifractal parameters were significantly different in acidotic
      and nonacidotic fetuses, independently from FHR pattern.

PMID- 21089008
TI  - Performance of estimated glomerular filtration rate prediction equations in
      preeclamptic patients.
AB  - Accurate estimation of the glomerular filtration rate (GFR) in patients with
      preeclampsia requires the collection of a 24-hour urine and can have important
      therapeutic and diagnostic implications. This procedure is often difficult or
      impossible to accomplish in this patient group. In this study, the Cockcroft
      Gault, the Modification of Diet in Renal Disease (MDRD), and Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) formulas were evaluated for their
      accuracy in determining GFR in the setting of preeclampsia. The estimated GFRs
      calculated from the above formulas were compared with the creatinine clearance
      values obtained from a 24-hour urine collections in 543 preeclamptic patients
      recruited from several large hospitals. Additionally, a set of new equations,
      preeclampsia GFR (PGFR), based on ethnicity, was created. The Cockcroft-Gault,
      MDRD, and CKD-EPI formulas were inaccurate in predicting GFR and both were
      significantly less accurate than PGFR. The latter formula provided an estimated
      GFR that was much closer to the creatinine clearance. Current GFR estimation
      equations based on serum creatinine values in nonpregnant patients are not
      reliable measures of renal function in patients with preeclampsia. The use of a
      new formula (PGFR) is recommended.

PMID- 21089009
TI  - [Do we really have to classify every gastrointestinal stroma tumour (GIST) by
      molecular analysis?].

PMID- 21089010
TI  - [The development of health information with the involvement of consumers at the
      German Institute for Quality and Efficiency in Health Care (IQWiG)].
AB  - The German Institute for Quality and Efficiency in Health Care (IQWiG) began
      publishing free bi-lingual (German/English) evidence-based health information in
      February 2006 on the website, http://www.gesundheitsinformation.de
      http://www.informedhealthonline.org . The Institute aims to be a patient-centred
      and non-directive provider of health information to the public and patients. The
      point of view and information needs of the public are a central element in the
      development of health information. People can be involved implicitly or
      explicitly. People can participate directly or explicitly in health information,
      for example, by suggesting a topic, by helping shape the content and during the
      development process. We do this in several ways, including surveys, consultation
      with consumer representatives as well as through user-testing and reader online
      rating. In addition, implicit involvement of patients occurs indirectly through
      consideration of the experiences and information needs of patients via an
      analysis of qualitative research. A challenge here is the generalisability of
      information derived from research in other cultures. The Institute monitors
      methodological developments in the area of patient and health information, to
      keep its methods up-to-date. In addition, the colleagues involved in this work
      participate in an in-house training program on patient-centred health
      information.

PMID- 21089011
TI  - [GambiaDentCare - evaluation of a primary oral health-care programme in West
      Africa].
AB  - STUDY AIM: Atraumatic restorative treatment, developed in the mid 1980s, was a
      milestone in primary oral health care in developing countries. In 2001, the basic
      package of oral care was implemented in Gambia (West Africa) by training nurses
      to become community oral health workers. It was therefore the aim of this study
      to evaluate the processes of the operative units of this programme. METHODS: The
      study was conducted in the form of a visitation, an employee attitude survey, and
      an analysis of the medical records. RESULTS: The evaluation revealed a continuous
      oral health care by competent community oral health workers in 5 out of 8 units.
      The patient catchment area considerably exceeded the village limits.
      Predominantly, pain therapy as a result of dental caries was administered with a
      restoration-extraction ratio of 1:10. Within a 12-month period, 5,524 patients of
      all ages were treated. The dental supply rate was 35%. CONCLUSIONS: Health care
      delivery in a primary oral health-care programme in the Repubilc of Gambia with
      community oral health workers was rated successfully. There is room for
      improvement in the organisational supervision of the operative units. The
      curriculum of future trainings should be adapted to changing epidemiological
      trends.

PMID- 21089014
TI  - Clinical staging of HIV infection as a surrogate for CD4 count in HIV-infected
      children.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is a major cause of
      infant and childhood mortality and morbidity; without treatment about 50% of them
      will succumb to HIV/AIDS before the age of two years. OBJECTIVE: to evaluate the
      usefulness of clinical manifestations of HIV infection as a surrogate for CD4
      counts in antiretroviral-naive HIV-infected children. METHODS: newly diagnosed
      HIV-infected children, antiretroviral-naive attending a paediatric infectious
      diseases unit were enrolled. The clinical manifesta-tions, age, sex, and WHO
      clinical stage of each patient were determined. CD4 count and CD4% were estimated
      at presentation and correlated with various clinical manifestations of HIV
      disease. RESULTS: the study population consisted of 126 children, aged four
      months to 14 years with a mean of 3.2 +/- 2.7 years and a male to female ratio of
      1.2:1. Eighty-one percent of the children acquired HIV infection through mother
      to-child transmission (MTCT). The CD4% was higher in infants (p < 0.000) and
      lower in children over five years of age. Eighty-six percent of them in stage 4
      were children less than 24 months of age. CD4% showed a modest correlation with
      WHO paediatric clinical staging (r=0.62, p=0.002). Patients with lymphadenopathy
      (stage 1) had a high absolute CD4 count whereas patients with failure to thrive
      had a relatively low absolute CD4 count. CONCLUSION: WHO Paediatric clinical
      staging for HIV infection correlates with CD4% and can be used as a surrogate to
      CD4. CD4 count and CD4% vary with age and complications of the disease.

PMID- 21089015
TI  - Management of febrile neutropenia in patients receiving chemotherapy for solid
      tumors: a retrospective study of twenty cases from the radiotherapy centre,
      Accra, Ghana.
AB  - BACKGROUND: One in ten patients on anticancer medication will develop febrile
      neutropenia irrespective of tumour type. There is need to protect our patients
      from this fatal condition while optimising chemotherapy. This may be difficult
      for a poor country. OBJECTIVE: to assess the management of cancer patients with
      febrile neutropenia in a low resource setting. METHODS: records of 20 cancer
      patients with febrile neutropenia (fn) over a three-year period were
      retrospectively analysed. data retrieved included age, sex, type of cancer and
      number of cycles of chemotherapy taken. Other parameters included initial
      temperature, site of infection, absolute neutrophil count (ANC) at presentation
      and antibiotic choice. Use of antifungal drugs, duration of fever and overall
      treatment outcome were also assessed. RESULTS: the male : female ratio was 3:2
      with a median age of 24 years (range: 15 - 68 years), and a mean temperature of
      38.8 oC (range 38.0-39.8 0C). Mean absolute neutrophil count was 0.2 x 109
      (range: 0.0 to 0.6 x 109). Thirteen (65%) received Cisplatin, five (25%) received
      Adriamycin, two (10%) received Paclitaxel or Cyclophosphomide-Methotrexate-5,
      Fluorouracil (CMF). Ten(50%) developed FN with the first cycle of chemotherapy,
      and six(30%) in the second cycle. Twelve (60%) had oral infection, four(20%) had
      gastroenteritis and single episodes of respiratory and urinary tract infections.
      Eleven (55%), received Ceftriaxone and Gentamycin, five (25%) cases received
      Levofloxacin or ciprofloxacin and Amoxicillin/clavunate + metronidazole; two
      cases(10%), Ceftazidime and Gentamycin; two cases(10%) received Meropenem. Twelve
      (60%) patients had antifungal therapy for oral candidiassis. Eight (40%) patients
      received growth factors. The mean fever duration was 4.5 days (range 1-10 days).
      Two (10%) of the patients died. CONCLUSION: febrile neutropenia in resource
      limited countries can be managed with good history and physical examination
      skills. Aminoglycosides are important components of empiric treatment in Ghana.

PMID- 21089013
TI  - Vesicovaginal fistula: a review of nigerian experience.
AB  - BACKGROUND: Vesicovaginal fistula is a preventable calamity, which has been an
      age-long menace in developing countries. OBJECTIVE: To review the causes,
      complications, and outcome of Vesicovaginal fistula in Nigeria. METHODS: Studies
      on Vesicovaginal fistula were searched on the internet. Information was obtained
      on PubMed(medline), WHO website, Bioline International, African Journal of Line,
      Google scholar, Yahoo, Medscape and e Medicine. RESULTS: Many Nigerian women are
      living with Vesicovaginal fistula. The annual obstetric fistula incidence is
      estimated at 2.11 per 1000 births. It is more prevalent in northern Nigeria that
      southern Nigeria. Obstetric fistula accounts for 84.1%-100% of the Vesicovaginal
      fistula and prolonged obstructed labour is consistently the most common cause
      (65.9%-96.5%) in all the series. Other common causes include caesarean section,
      advanced cervical cancer, uterine rupture, and Gishiri cut. The identified
      predisposing factors were early marriage and pregnancy, which were rampant in
      northern Nigeria, while unskilled birth attendance and late presentation to the
      health facilities was common nationwide. Among the significant contributory
      factors to high rate of unskilled birth attendance and were poverty, illiteracy,
      ignorance, restriction of women's movement, non-permission from husband and
      transportation. All but one Nigerian studies revealed that primiparous women were
      the most vulnerable group. Pregnancy outcome was dismal in most cases related to
      delivery with still birth rate of 87%-91.7%. Stigmatization, divorce and social
      exclusion were common complications. Overall fistula repair success rate was
      between 75% and 92% in a few centres that offer such services. CONCLUSION:
      Vesicovaginal fistula is prevalent in Nigeria and obstetric factors are mostly
      implicated. It is a public health issue of concern.

PMID- 21089017
TI  - Residents' perception of postgraduate radiology training in Nigeria.
AB  - BACKGROUND: literature on radiology residency in Nigeria is sparse, even for
      decades after its commencement. There is therefore the need to inquire into the
      problems and prospects of the programme, at least from the perspectives of the
      residents. OBJECTIVE: to determine residents' perception of the radiology
      residency programme, residents' view on state of facilities, and their opinion on
      the future of radiology training in Nigeria. METHODS: Self-administered semi
      structured questionnaires, were given to residents to complete. Contacts were
      made with residents during update courses and radiologists' conferences or
      meetings. RESULTS: one hundred and twenty-five questionnaires were given out and
      120 were completed and returned, giving a response rate of 96 %. Fifty-eight
      (48%) respondents mentioned academic interest as the major influencing factor for
      enrolling into the programme. Only 20 (16%) residents had made up their minds to
      do radiology residency as medical students. All the residents identified
      conventional radiography and ultrasound as the only regularly functioning
      modalities in their centres, while 72 (60%) respondents mentioned same for cross
      sectional imaging modalities; that is CT and MRI. One hundred and ten (90%)
      respondents had rotation through available modalities as the plank of their
      training programmes, and 96 (80%) did not feel happy about the state of teaching
      aids at their centres. Ninety-six (80%) of the residents expressed satisfaction
      at the efforts of the supervisory postgraduate medical colleges at organising
      update courses. Eighty respondents (65%) mentioned limited (or lack of) exposure
      to modern imaging modalities as the greatest threat to the future of radiology
      residency in Nigeria. CONCLUSION: nigerian radiology residents are concerned
      about lack of modern imaging tools, facilities at their centres, as well as
      opportunities for exposure overseas, and the likely impact of these on their
      training and the future of the specialty in Nigeria.

PMID- 21089016
TI  - Experience with extra-capsular cataract exraction and intra-ocular lens implant
      in children.
AB  - BACKGROUND: in developing countries congenital cataract has become an important
      cause of treatable blindness in childhood. However, difficulty in correcting
      aphakia is one of the reasons for poor visual outcome. OBJECTIVE: to determine
      the visual outcome after extra capsular cataract extraction and intra ocular lens
      implant and factors militating against good visual outcome in children. METHODS:
      a prospective interventional study of cataract extraction in children with intra
      ocular lens implant. Extra capsular cataract extraction with intra ocular lens
      implant was performed using the superior limbal approach. Polymethyl Methacrylate
      lenses were inserted. Posterior capsulotomy was done with a 25G needle bent at
      the tip in 26 eyes. RESULTS: thirty two eyes of twenty five children aged between
      4 months and 16 years were operated. Extra capsular cataract extraction with
      posterior chamber intraocular lens implant was done in 27 (83.4%) eyes, plain
      extra capsular cataract extraction in 3 (9.4%) eyes, extra capsular cataract
      extraction with anterior chamber intraocular lens implant in 1 (3.1%) eye and
      vectis extraction in 1 (3.1%) eye. Twenty six eyes had primary posterior
      capsulotomy. Thirty-two (100%) eyes and 15 (60%) children were blind before
      surgery. Result of post operative visual acuity in 18 children after refraction
      was 6/18 or better in 4 (22.2%) children 6/24-6/60 in 11 (61.1%) and< 3/60 in 3
      (16.7%) children. CONCLUSION: visual rehabilitation following extra capsular
      cataract extraction with Intra Ocular Lens Implant is encouraging in children.

PMID- 21089018
TI  - Obstetric outcome of teenage pregnancy in Kano, North-Western Nigeria.
AB  - BACKGROUND: teenage pregnancies are regarded as high risk, because they often
      occur outside marriage. There is the need to evaluate the outcome of teenage
      pregnancies in a predominantly Islamic society like Kano where most occur within
      marriage, and timely prenatal care is usually available to most of them.
      OBJECTIVE: to review the obstetric outcome of teenage primigravida in Aminu Kano
      Teaching Hospital, Kano, Nigeria. METHODS: a retrospective case-control study of
      500 booked teenage primigravidae, who delivered in our labour ward from January
      2002 to December 2005 (study group) was performed. Their obstetric outcome was
      compared with that of an equal number of booked primigravidae aged 20-34 years,
      who met the recruitment criteria and delivered immediately after a selected
      teenage mother (control group). The study variables of interest were the
      demographic characteristics of the women in the two groups, antenatal/intrapartum
      complications and neonatal outcome. RESULTS: there were no significant
      differences in the mean birth weight, mean gestational age at delivery, mean
      height and perinatal mortality between the two groups, but mean maternal weight
      and body mass index (BMI) were higher among the older women. The teenage mothers
      had increased incidence of preterm labour and low birth weight infants (P <
      0.05). The incidence of caesarean section and instrumental deliveries were lower
      among the teenage mothers. CONCLUSION: the results of this study show that
      teenage mothers who receive good family and community support, timely quality
      antenatal care and deliver in the hospital, should expect similar obstetric
      outcome to that of their older peers.

PMID- 21089019
TI  - Cranial computerised tomographic assessment of cerebrovascular disease in Osogbo,
      Nigeria.
AB  - BACKGROUND: cerebrovascular disease (CVD) is a leading cause of morbidity and
      mortality in Nigeria. Non-contrast computerized axial tomography (CT) is the
      routine imaging modality of choice for acute stroke evaluation, because it is
      widely accessible, convenient, has a short imaging time, and is sensitive for
      detection of haemorrhage. OBJECTIVE: to evaluate the pattern of stroke by
      computerised tomography (CT) and to relate the clinical diagnosis of stroke to
      the radiological features. METHODS: a retrospective study of 86 patients with
      suspected stroke who had CT of the brain from October 2005 to December 2008 were
      studied. The type and location of the stroke were documented and correlated with
      the age and sex. RESULTS: Sixty-five (75.6%) out of the 86 patients had CVD.
      Normal study was noted in 7(8.12%) patients and 14(16.3%) patients had other
      intracranial conditions wrongly diagnosed clinically as stroke. Ischaemic CVD was
      the most common [43(66.2%)], haemorrhagic CVD [21(32.3%)] and combined ischaemic
      and haemorrhagic, one(1.5%). Most [26(60.5%)] of the ischaemic stroke lesions
      were localized to the region of the middle and anterior cerebral arteries. There
      were no differences based on gender in the distribution of stroke pattern within
      the brain or the type of cerebrovascular disease. CONCLUSION: ischaemic CVD is
      the most common stroke. The rate of misdiagnosis of stroke is high in the Osogbo
      environment.

PMID- 21089020
TI  - Survey of blindness and low vision in Egbedore, South-Western Nigeria.
AB  - BACKGROUND: Developing efficient and cost-effective eye care programmes for
      communities in Nigeria has been hampered by inadequate and inaccurate data on
      blindness and low vision. OBJECTIVE: To determine the prevalence and causes of
      blindness and low vision among adults 50 years and older in South-Western Nigeria
      in order to develop viable eye care programme for the community. METHODS: Twenty
      clusters of 60 subjects of age 50 years and older were selected by systematic
      random cluster sampling. Information was collected and ocular examinations were
      conducted on each consenting subject. Data were recorded in specially designed
      questionnaire and analysed using descriptive statistical methods. RESULTS: Out of
      the 1200 subjects enrolled for the study, 1183(98.6%) were interviewed and
      examined. Seventy five (6.3%)) of the 1183 subjects were bilaterally blind and
      223(18.9%) had bilateral low vision according to WHO definition of blindness and
      low vision. Blindness was about 1.6 times commoner in men than women. Cataract,
      glaucoma and posterior segment disorders were major causes of bilateral
      blindness. Bilateral low vision was mainly due to cataract, refractive errors and
      posterior segment disorders. CONCLUSION: The prevalence of blindness and low
      vision in this study population was high. The main causes are avoidable.
      Elimination of avoidable blindness and low vision calls for attention and
      commitment from government and eye care workers in South Western Nigeria.

PMID- 21089021
TI  - Influence of performance status on the risk and outcome of nosocomial pneumonia
      in the elderly admitted to an open medical ward.
AB  - BACKGROUND: nosocomial pneumonia (NP) has been observed to complicate the course
      of management of some elderly patients in medical wards and this impacts
      negatively on the outcome of care of this group of patients. OBJECTIVE: to
      determine the relationship of pre-treatment performance status (PTPS) on the risk
      and outcome of NP in elderly patients admitted to an open medical ward. METHODS:
      a prospective clinical surveillance of all elderly patients admitted to the
      medical wards of a University Teaching Hospital was carried out over a period of
      nine years. RESULTS: in the nine-year period 531 patients; aged 65 to 107 years
      were seen, 184(34.7%) of whom developed NP. Eleven (21%) patients had PTPS of 75%
      or more (i.e. able to care for selves without assistance), one (0.2%) of whom
      developed NP. Seventy-eight (14.7%) patients had PTPS of 51-74% (i.e. required
      occasional assistance for routine care); 13(2.4%) of whom also developed NP. Of
      the 217 (40.9%) patients who had PTPS of 26-50% (i.e. requiring considerable
      assistance for self care), 73(13.7%) of them had NP while 97 (18.3%) out of 225
      patients with PTPS below 25% (i.e. completely dependent on others for routine
      care) developed nosocomial pneumonia. CONCLUSION: a low performance status score
      increases the risk of development of NP in the elderly and this risk is
      influenced by type of treatment-related interventions a patient has on admission.

PMID- 21089022
TI  - Reliability of urine multistix and gram stain in the detection of asymptomatic
      bacteriuria in pregnancy.
AB  - BACKGROUND: urinary tract infection is a common problem during pregnancy.
      Asymptomatic bacteriuria can cause the development of serious complications
      affecting both the mother and foetus. Urine culture, the traditional screening
      test is relatively expensive, time consuming and requires a microbiology
      laboratory and trained staff. However simpler, less expensive tests which include
      urine multistix and urine gramstain better suited for developing countries are
      available. OBJECTIVE: to determine the sensitivity, specificity and predictive
      values of multistix nitrite, leucocyte esterase (LE) and urine gram staining for
      asymptomatic bacteriuria in pregnancy. METHODS: A cross-sectional study was
      carried out from 1st July to 31st October 2007, at the University of Ilorin
      Teaching Hospital (UITH) on 125 consenting asymptomatic pregnant women. A
      structured proforma was used to collect information from the women and a
      midstream urine specimen collected in two sterile bottles. One was tested with
      Multistix(r) for the presence of nitrite and leucocyte esterase and the other for
      bacteriological culture and urine gram stain. RESULTS: using the gold standard of
      urine culture, the sensitivities of Multistix(r) nitrite and leucocyte esterase
      were each 14% and the specificity 100% and 96% respectively. Urine gram stain had
      a sensitivity of 98% and a specificity of 74.7%. CONCLUSION: multistix(r) nitrite
      and leucocyte esterase are not sufficiently sensitive to be used as a screening
      tool for asymptomatic bacteriuria. Urine gram stain can be used in areas where
      facilities are inadequate for culture but cannot replace it. More studies are
      required to determine the accuracy of urine gram-stain.

PMID- 21089023
TI  - Impact of hypertension on sexual function in women.
AB  - BACKGROUND: the effect of hypertension and its treatment on female sexual
      function is largely unexplored especially in Africa. However in practice, cases
      abound where consequent sexual dysfunction leads to poor or non-adherence with
      catastrophic results. Believing that like in males, hypertension and its
      treatment should affect female sexual function; we set out using a structured
      questionnaire to study the subject as it affects women. OBJECTIVE: to examine the
      relationship between hypertension and female sexual functions of arousal,
      lubrication and orgasm. METHODS: five hundred questionnaires were distributed to
      consenting Nigerian women after ethical clearance was obtained. Information
      sought included demographics, menstrual history, medical treatment and sexual
      function. RESULTS: a total of 454 returned questionnaires were analysable. Out of
      this, 109(24%) admitted to being hypertensive, 89 of whom were on treatment.
      Hypertension was related to difficulty with sustaining sexual excitement
      (p=0.03), decreased sexual thoughts (p=0.003), poor rating of marriages (p=0.03),
      difficulty being excited by fantasies (p=0.0001), increased vaginal dryness in
      the preceding one year (p=0.02), reduced frequency of sexual contact in the last
      one year (p=0.04) and rejection of partner sexual advance (p=0.05). The
      proportion of women in regular sexual relationship was less among the
      hypertensive group (p=0.02). Use of drugs produced significant sexual
      unpleasantness (p=0.03). CONCLUSION: hypertension and its treatment may produce
      female sexual dysfunction, and should be considered in managing the female
      hypertensive. By so doing, quality of life can be maintained; and compliance
      improved upon. The cumulative effect would be improvement in blood pressure
      control, with its attendant reduction in morbidity and mortality from
      hypertension.

PMID- 21089024
TI  - Ectopic pregnancy following in vitro fertilisation and embryo transfer.
AB  - BACKGROUND: ectopic pregnancy is one of the recognised complications of in vitro
      fertilisation (IVF) and embryo transfer. OBJECTIVE: to review cases of ectopic
      pregnancy following IVF at a fertility unit, with the aim of raising awareness
      towards its increased incidence and pattern of presentation. METHODS: case
      records of patients who had ectopic pregnancy following IVF over a three-year
      period (July 2005-June 2008) were retrieved from the medical records department.
      Data including age, parity, risk factors for ectopic pregnancy as well as
      management modality were extracted and analysed. RESULTS: There were 64 clinical
      pregnancies during the study period. Of these, five were ectopic pregnancies,
      given a frequency of 7.8%. The minimum number of embryos transferred was two and
      maximum four. All the five cases had easy embryo transfer. There was one case of
      heterotopic pregnancy. Two (40%) patients had previous ectopic pregnancies with
      one having a third ectopic pregnancy despite previous bilateral salpingectomies.
      Four (80%) of the five cases had laparotomy done. Three (60%) cases had ruptured
      ectopic pregnancies. One case was managed conservatively with methotrexate.
      CONCLUSION: ectopic pregnancy can present following IVF procedures. A high index
      of suspicion is necessary even in cases with previous bilateral salpingectomies
      or easy embryo transfer.

PMID- 21089025
TI  - Ileal endometriosis presenting as acute small intestinal obstruction: a case
      report.
AB  - BACKGROUND: the gastrointestinal tract is the most common site of extrapelvic
      endometriosis, affecting 5%-15% of women with pelvic endometriosis. Among women
      with intestinal endometriosis, rectum and sigmoid colon are the most commonly
      involved areas. Terminal ileum is rarely involved in endometriosis. Similarly,
      bowel endometriosis is an uncommon cause of intestinal obstruction. OBJECTIVE: to
      present a rare occurrence of ileal endometriosis presenting with acute small
      intestinal obstruction. METHODS: a 34-year-old woman presented with a two-month
      history of intermittent, colicky abdominal pain which became more intense with
      associated vomiting of three days prior to presentation. Besides full clinical
      evaluation, she had other investigations including abdominal X-rays,
      ultrasonography, ECG, and echocardiography. The results of these informed the
      need for myomectomy. RESULTS: besides the abdominal pain, the patient also
      complained of a supra-pubic swelling and menorrhagia. Physical examination showed
      an incisional hernia, and a suprapubic mass. The results of evaluation were
      consistent with incisional hernia complicated by imminent adhesive intestinal
      obstruction. She had had secondary infertility and has had myomectomy due to
      copious menstrual flow which was complicated with incisional hernia. She was
      managed initially conservatively for adhesive small bowel obstruction which
      failed. She had exploratory laparotomy with small intestinal resection and end to
      end anastomosis. Histopathology of the resected mass revealed ileal
      endometriosis. CONCLUSION: this report highlights the importance of
      histopathological assessment of resected specimens in the diagnosis of intestinal
      obstruction due to intestinal endometriosis. This disease should, therefore, be
      considered during the evaluation of women of child bearing age.

PMID- 21089026
TI  - A human tail in an infant (letter).

PMID- 21089027
TI  - Non-syndromic oligodontia: a case report.
AB  - BACKGROUND: oligodontia is a condition with developmental absence of six or more
      permanent teeth excluding the third molars. It is a rare finding which has not
      been frequently documented in Nigerian children. OBJECTIVE: to report a case of
      non syndromic oligodontia. METHODS: The details of the clinical presentation,
      course and outcome of a 9-year-old child with oligodontia were reviewed. The
      child was fully assessed clinically and orthopantomography was done. RESULTS:
      extra-oral examination revealed no abnormalities of the skin , hair, or nails.
      Intra orally, the primary canines and molars, the permanent upper left canine and
      permanent first molars were present. Carious lesions were seen on the primary
      molars present. An orthopantomograph revealed that thirteen permanent teeth were
      absent excluding the third molars. The carious primary molars were restored with
      glass ionomer cement and upper and lower acrylic partial dentures were fabricated
      for the patient. The importance of preventive measures and regular dental follow
      up was stressed. Mother was educated about probable treatment options for future
      dental management of the growing child. CONCLUSION: the consequences of missing
      teeth include abnormal occlusions or altered facial appearance which can cause
      psychological distress for some patients. For this reason, early diagnosis is
      important to prevent consequences of aesthetic and functional problems in the
      dentition.

PMID- 21089036
TI  - T4 virus-based toolkit for the direct synthesis and 3D organization of metal
      quantum particles.
AB  - One of the challenges in building superstructures based on small metal particles
      is producing stable interparticle separation. Herein, we present a novel assembly
      method based on the use of the T4 bacteriophage capsid as a scaffold for the
      construction of 3D monodisperse metal-particle arrays. The highly regular and
      symmetrical protein surface of the T4 capsid allows the site-directed adsorption
      and subsequent reduction of metal ions, thus permitting the growth of metal
      particles in situ to enable them to exist at a quantum size with a high degree of
      monodispersity. Both these characteristics contribute to a great improvement in
      the electrocatalytic activity of the patterned noble-metal particles. Organized
      magnetic particles as small as 2-4 nm still maintain an observable ferromagnetic
      behavior, which makes them promising for a variety of possible biomedical
      applications.

PMID- 21089028
TI  - A cross-species analysis of Satb2 expression suggests deep conservation across
      vertebrate lineages.
AB  - Mutation of SATB2 causes cleft palate in humans. To understand the role of SATB2
      function in palatogenesis, SATB2 analyses in vertebrate model systems will be
      essential. To facilitate these analyses, we have performed a cross-species
      comparison of SATB2 structure and function across three vertebrate model systems:
      mouse, chick, and zebrafish. We find that the SATB2 transcript is highly
      conserved across human, mouse, chick, and zebrafish, especially within the Satb2
      functional domains. Furthermore, our expression analyses demonstrate that SATB2
      is likely to have similar functions in vertebrate model organisms and humans
      during development of the facial processes and secondary palate. Together, these
      data suggest an evolutionary conserved role for SATB2 during development of the
      face and palate across vertebrates. Moreover, expression of zebrafish satb2 in
      the anterior neurocranium supports the utility of the anterior neurocranium as a
      simplified model of amniote palatogenesis.

PMID- 21089041
TI  - Gold-catalyzed direct activation of allylic alcohols in the stereoselective
      synthesis of functionalized 2-vinyl-morpholines.

PMID- 21089037
TI  - A minimalist NMR approach for the structural revision of mucoxin.
AB  - In an attempt to revise the structural assignment of mucoxin, and faced with 64
      diastereomeric possibilities, we resorted to the synthesis of truncated
      structures that contained the core stereochemical sites. Twelve stereochemical
      analogues were synthesized, their (1)H and (13)C NMR spectra were analyzed and
      four recurring stereochemical trends were distilled from the data. Applying the
      observed trends to the diastereomeric population pared the possible choices for
      the correct structure of mucoxin from 64 to 4. Synthesis of these analogues led
      to the identification of the correct structure of mucoxin.

PMID- 21089045
TI  - Explaining high-frequency hearing.

PMID- 21089046
TI  - Angiogenesis of the frozen-thawed human fetal ovarian tissue at the early stage
      after xenotransplantation and the positive effect of Salviae miltiorrhizae.
AB  - Cryopreserving ovarian tissue followed by transplantation has been suggested to
      preserve fertility for young cancer survivors. However, ischemia in the early
      stage after transplantation causes massive follicle loss. The aim was to
      investigate the histological and ultrastructural characteristics of the frozen
      thawed human fetal ovarian tissue after xenotransplantation and the effects of
      Salviae miltiorrhizae (SM) on the angiogenesis. The human fetal ovarian tissues
      were frozen-thawed, xenografted into the immunodeficient nu/nu mice, and then
      collected 2, 7, and 28 days after transplantation. SM was administered. Compared
      with that of the frozen-thawed ovarian tissue, the total follicle number of the
      grafts was greatly reduced. Nearly half of the primordial follicles were damaged
      at different levels on day 2. Moreover, edema was prevalent in the stroma during
      the first week after the graft, especially on day 2. The microvessel density of
      the grafts was increased on day 2, reached a peak on day 7, and then declined on
      day 28. Both healthy primordial follicle proportion and the total healthy
      primordial follicles pool in the SM group were significantly higher than those of
      the control group (P = 0.003 and P = 0.001). We found a statistically significant
      difference of microvessel density between the two groups on day 2 (P < 0.001). In
      the frozen-thawed fetal ovarian grafts, angiogenesis has been begun on day 2, and
      the first week is the critical time for the grafts to regain their function, in
      which SM can facilitate graft vascularization and improve the preservation of
      primordial follicles.

PMID- 21089048
TI  - Protein abundances are more conserved than mRNA abundances across diverse taxa.
AB  - Proteins play major roles in most biological processes; as a consequence, protein
      expression levels are highly regulated. While extensive post-transcriptional,
      translational and protein degradation control clearly influence protein
      concentration and functionality, it is often thought that protein abundances are
      primarily determined by the abundances of the corresponding mRNAs. Hence
      surprisingly, a recent study showed that abundances of orthologous nematode and
      fly proteins correlate better than their corresponding mRNA abundances. We tested
      if this phenomenon is general by collecting and testing matching large-scale
      protein and mRNA expression data sets from seven different species: two bacteria,
      yeast, nematode, fly, human, and rice. We find that steady-state abundances of
      proteins show significantly higher correlation across these diverse phylogenetic
      taxa than the abundances of their corresponding mRNAs (p=0.0008, paired
      Wilcoxon). These data support the presence of strong selective pressure to
      maintain protein abundances during evolution, even when mRNA abundances diverge.

PMID- 21089047
TI  - Protein expression profiles distinguish between experimental invasive pulmonary
      aspergillosis and Pseudomonas pneumonia.
AB  - We hypothesized that invasive pulmonary aspergillosis (IPA) may generate a
      distinctive proteomic signature in plasma and bronchoalveolar lavage (BAL).
      Proteins in plasma and BAL from two neutropenic rabbit models of IPA and
      Pseudomonas pneumonia were analyzed by SELDI-TOF MS. Hierarchical clustering
      analysis of plasma time course spectra demonstrated two clusters of peaks that
      were differentially regulated between IPA and Pseudomonas pneumonia (57 and 34
      peaks, respectively, p<0.001). PCA of plasma proteins demonstrated a time
      dependent separation of the two infections. A random forest analysis that ranked
      the top 30 spectral points distinguished between late Aspergillus and Pseudomonas
      pneumonias with 100% sensitivity and specificity. Based on spectral data
      analysis, three proteins were identified using SDS-PAGE and LC/MS and quantified
      using reverse phase arrays. Differences in the temporal sequence of plasma
      haptoglobin (p<0.001), apolipoprotein A1 (p<0.001) and transthyretin (p<0.038)
      were observed between IPA and Pseudomonas pneumonia, as was C-reactive protein
      (p<0.001). In summary, proteomic analysis of plasma and BAL proteins of
      experimental Aspergillus and Pseudomonas pneumonias demonstrates unique protein
      profiles with principal components and spectral regions that are shared in early
      infection and diverge at later stages of infection. Haptoglobin, apolipoprotein
      A1, transthyretin, and C-reactive protein are differentially expressed in these
      infections suggesting important contributions to host defense against IPA.

PMID- 21089050
TI  - Microsurgical anatomy of lumbosacral nerve rootlets for highly selective
      rhizotomy in chronic spinal cord injury.
AB  - It is known that selective sacral roots rhizotomy is effective for relieving the
      neurogenic bladder associated with spinal cord injury. The goal of this study is
      to review the surgical anatomy of the lumbosacral nerve rootlets and to provide
      some morphological bases for highly selective sacral roots rhizotomy. Spinal cord
      dissections were performed on five cadavers under surgical microscope. At each
      spinal cord segment, we recorded the number, diameter and length of the rootlets,
      subbundles and bundles from the L1 to S2 spinal segments, and the length of the
      dorsal/ventral root entry zone. Peripheral nervous system myelin was examined by
      immunohistochemistry. We found: (1) the ventral or the dorsal root of the
      lumbosacral segment of the spinal cord was divided into one to three nerve
      bundles and each bundle was subdivided into one to three subbundles. Each
      subbundle further gave out two to three rootlets connected with the spinal cord;
      (2) there were no significant differences in the number of rootlets within the L1
      to S2 segments, but the size of rootlets and the length of nerve roots varied (P
      < 0.05); and (3) the more myelinated fibers a rootlet contained, the larger
      transection area it had. The area of peripheral nervous system myelin positive
      cells and the total area of rootlets were correlated (P < 0.001). Thus, during
      highly selective sacral roots rhizotomy, the ventral and dorsal roots can be
      divided into several bundles of rootlets, and we could initially distinct the
      rootlets by their diameters.

PMID- 21089051
TI  - Detection of Abeta plaques by a novel specific MRI probe precursor CR-BSA-(Gd
      DTPA)n in APP/PS1 transgenic mice.
AB  - Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). The lack of
      specific probes that can detect individual senile plaques in AD has prompted the
      development of magnetic resonance imaging (MRI) probes. In this study, based on
      DTPA-gadolinium (III) and congo red (CR), a novel specific MRI probe precursor CR
      BSA-(Gd-DTPA)n was successfully synthesized. Its ability to bind to amyloid
      plaques was evaluated by brain sections from APP/PS1 transgenic mice. Its
      specificity for Abeta plaques was further demonstrated by immunohistochemistry
      (IHC) staining with the monoclonal antibody to the Abeta protein. Meanwhile, the
      amyloid deposits detected by the CR-BSA-(Gd-DTPA)n were matched to the amyloid
      deposits detected by Abeta specific antibody. We also found that a few amyloid
      like deposits which was not detected by IHC. The findings indicated that the
      probe perhaps could detect the neurofibrillary tangles (NFT) similar to the
      effect of CR itself, and this will be verified in future experiments. The works
      suggested that the Abeta protein-specific magnetic resonance contrast agent
      precursor CR-BSA-(Gd-DTPA)n can be used as a potential fluorescence and MR multi
      modal imaging probe precursor to display individual senile plaques in AD.

PMID- 21089054
TI  - Acteoside inhibits PMA-induced matrix metalloproteinase-9 expression via CaMK/ERK
      and JNK/NF-kappaB-dependent signaling.
AB  - SCOPE: Acteoside, an active phenylethanoid glycoside found in bitter tea and many
      medicinal plants, displays chemopreventive properties. The aim of our study was
      to determine the effect of acteoside on tumor invasion and migration; the
      possible mechanisms involved in this inhibition were investigated in human
      fibrosarcoma HT-1080 cells. METHODS AND RESULTS: We employed invasion, migration
      and gelatin zymography assays to characterize the effect of acteoside on HT-1080
      cells. Transient transfection assays were performed to investigate gene promoter
      activities, and immunoblot analysis to study its molecular mechanisms of action.
      We found that acteoside suppresses phorbol-12-myristate-13-acetate (PMA)-enhanced
      matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and
      transcriptional levels through the suppression of NF-kappaB activation. In
      addition, acteoside repressed the PMA-induced phosphorylation of ERK1/2 (ERK,
      extracellular regulated kinase) and JNK1/2. Further, we found that acteoside
      decreased the PMA-induced influx of Ca(2+) and repressed PMA-induced calmodulin
      dependent protein kinase (CaMK) phosphorylation. Furthermore, treatment with
      BAPTA/AM, W7, or capsazepine markedly decreased PMA-induced MMP-9 secretion and
      cell migration, as well as ERK and JNK/NF-kappaB activation. CONCLUSION:
      Acteoside inhibited PMA-induced invasion and migration of human fibrosarcoma
      cells via Ca(2+) -dependent CaMK/ERK and JNK/NF-kappaB-signaling pathways.
      Acteoside therefore has the potential to be a potent anticancer agent in
      therapeutic strategies for fibrosarcoma metastasis.

PMID- 21089057
TI  - Determination of uric acid in human urine by capillary zone electrophoresis with
      indirect laser-induced fluorescence detection.
AB  - A CZE with indirect LIF detection method was used for the determination of uric
      acid (UA) in human urine. UA and its coexisting analytes (i.e. hypoxanthine,
      xanthine and ascorbic acid) could be well separated within 4.5 min at a voltage
      of 25 kV with 25 degrees C cartridge temperature in a running buffer composed of
      5 mM sodium borate, 10% methanol (v/v) and 0.3 MUM fluorescein sodium (apparent
      pH of the final mixed hydro-organic solution of sodium borate, methanol and
      fluorescein is 9.5). Under the optimum condition, the method has good linearity
      relationships (correlation coefficients: 0.9973-0.9987) with ranges of 25-500, 25
      350, 25-250 and 25-300 MUg/mL for hypoxanthine, ascorbic acid, xanthine and UA,
      respectively. The detection limits for the analytes were in the range of 0.29
      0.90 MUg/mL. The intra-day RSD values for migration times and peak areas were
      less than 0.43 and 3.27%, respectively. This method was applied to the
      quantitation of UA in human urine with recoveries in the range of 93.1-107.3%.

PMID- 21089052
TI  - Expression of matrix metalloproteinase-9 mRNA and vascular endothelial growth
      factor protein in gastric carcinoma and its relationship to its pathological
      features and prognosis.
AB  - To investigate matrix metalloproteinase-9 (MMP-9) mRNA and vascular endothelial
      growth factor (VEGF) protein expression in gastric carcinoma and its correlation
      with microvascular density, growth-pattern, invasion, metastasis, and prognosis.
      In situ hybridization of MMP-9 mRNA and immunohistochemistry of VEGF and CD34
      proteins were performed on surgical specimens of gastric cancers from 118
      patients compared with 20 nonmalignant gastric mucosae. Their relationships to
      pathological parameters and survival times were determined by statistical
      analysis. The positive rate of MMP-9 in noncancerous gastric mucosae was
      significantly lower than that of gastric cancer tissue (60.17%, P < 0.01). In
      patients with cancers of the infiltrating type, at stage T3-T4, with vessel
      invasion, lymphatic metastasis, hepatic, or peritoneal metastasis, the positive
      expression rates of MMP-9 mRNA, VEGF protein, and CD34 were significantly higher
      than those for patients with tumors of the expanding type (P < 0.01), at stage T1
      T2 (P < 0.01), with nonvessel invasion (P < 0.05), without lymphatic metastasis
      (P < 0.05), and without hepatic (P < 0.001) or peritoneal metastasis (P < 0.001),
      respectively. Expression of MMP-9 mRNA was positively related to that of VEGF
      protein (P < 0.001) and microvascular density (P < 0.001). Patients with higher
      MMP-9 mRNA and VEGF expression demonstrated vivid tumor angiogenesis and poor 5
      year survival rate. MMP-9 and VEGF expression is associated with enhanced tumor
      angiogenesis and may play crucial roles in the invasion and metastasis of gastric
      carcinoma. Therefore, MMP-9 and VEGF may represent prognostic biomarkers and
      promising targets for therapeutic intervention.

PMID- 21089060
TI  - New approaches of LC-MS compatible method development on alpha(1)-acid
      glycoprotein-based stationary phase for resolution of enantiomers by HPLC.
AB  - Protein-based chiral stationary phases, in particular alpha(1)-acid glycoprotein,
      are chromatographic materials with a very broad application range. The chiral
      recognition ability of this selector allows the resolution of more than 90% of
      the molecules tested. A step-by-step description of the screening approach that
      we have developed is described in this article with two objectives in mind:
      obtaining a high success rate with a straightforward methodology that can be
      generally applied and allowing LC-MS compatibility. Second, the screening
      strategy is required to take into account the main functional nature of the
      racemic compound to be resolved (neutral, acidic or basic) for method
      optimisation step, but should be independent of other structural features, in
      order to allow the routine application of screening sequences and the application
      to the largest number of samples.

PMID- 21089061
TI  - Trilinear multiplicative modelling of thin layer chromatography retention as a
      function of solute, organic modifier and its concentration.
AB  - We have recently shown in a preliminary study, that the retention in TLC,
      expressed as R(F) values, can be modelled in multiplicative trilinear way (solute
      * mobile phase * stationary phase), explaining almost all variance. Such
      possibility did not occur in the case of k or R(M) values. This paper is a
      continuation of investigation about this phenomenon. We perform here a trilinear
      decomposition of two datasets (normal-phase and RP) of 35 model compounds
      organized differently as in the previous study: solute * modifier *
      concentration. The resulted models explain 96.8% of whole variance on silica and
      90.33% of RP18 variance. No strict correlation with any particular molecular
      descriptor was found, although the mean electrotopological state index (Ms) was
      fairly correlated with RP contributions. The results confirm definitively a
      general possibility to model TLC retention in a multiplicative manner and inspire
      for further research in this field.

PMID- 21089062
TI  - Long-term antimicrobial effect of silicon nanowires decorated with silver
      nanoparticles.

PMID- 21089063
TI  - When function follows form: Effects of donor copolymer side chains on film
      morphology and BHJ solar cell performance.

PMID- 21089064
TI  - Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric
      aciduria Type 2, is caused by a microdeletion in the riboflavin transporter gene
      GPR172B.
AB  - Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD)
      and flavin mononucleotide (FMN) molecules, required in biological oxidation
      reduction reactions. We previously reported a case of a newborn female who had
      clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency
      (MADD), which was corrected by riboflavin supplementation. The mother was then
      found to be persistently riboflavin deficient, suggesting that a possible genetic
      defect in riboflavin transport in the mother was the cause of the transient MADD
      seen in the infant. Two recently-identified riboflavin transporters G protein
      coupled receptor 172B (GPR172B or RFT1) and riboflavin transporter 2 (C20orf54 or
      RFT2) were screened for mutations. Two missense sequence variations, c.209A>G
      [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional
      studies of both missense variations showed that riboflavin transport was
      unaffected by these variations. Quantitative real-time PCR revealed a de novo
      deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We
      postulate that haploinsufficiency of this riboflavin transporter causes mild
      riboflavin deficiency, and when coupled with nutritional riboflavin deficiency in
      pregnancy, resulted in the transient riboflavin-responsive disease seen in her
      newborn infant. This is the first report of a genetic defect in riboflavin
      transport in humans.

PMID- 21089065
TI  - Recommendations for genetic variation data capture in developing countries to
      ensure a comprehensive worldwide data collection.
AB  - Developing countries have significantly contributed to the elucidation of the
      genetic basis of both common and rare disorders, providing an invaluable resource
      of cases due to large family sizes, consanguinity, and potential founder effects.
      Moreover, the recognized depth of genomic variation in indigenous African
      populations, reflecting the ancient origins of humanity on the African continent,
      and the effect of selection pressures on the genome, will be valuable in
      understanding the range of both pathological and nonpathological variations. The
      involvement of these populations in accurately documenting the extant genetic
      heterogeneity is more than essential. Developing nations are regarded as key
      contributors to the Human Variome Project (HVP;
      http://www.humanvariomeproject.org), a major effort to systematically collect
      mutations that contribute to or cause human disease and create a cyber
      infrastructure to tie databases together. However, biomedical research has not
      been the primary focus in these countries even though such activities are likely
      to produce economic and health benefits for all. Here, we propose several
      recommendations and guidelines to facilitate participation of developing
      countries in genetic variation data documentation, ensuring an accurate and
      comprehensive worldwide data collection. We also summarize a few well-coordinated
      genetic data collection initiatives that would serve as paradigms for similar
      projects.

PMID- 21089066
TI  - Assessment of copy number variation using the Illumina Infinium 1M SNP-array: a
      comparison of methodological approaches in the Spanish Bladder Cancer/EPICURO
      study.
AB  - High-throughput single nucleotide polymorphism (SNP)-array technologies allow to
      investigate copy number variants (CNVs) in genome-wide scans and specific calling
      algorithms have been developed to determine CNV location and copy number. We
      report the results of a reliability analysis comparing data from 96 pairs of
      samples processed with CNVpartition, PennCNV, and QuantiSNP for Infinium Illumina
      Human 1Million probe chip data. We also performed a validity assessment with
      multiplex ligation-dependent probe amplification (MLPA) as a reference standard.
      The number of CNVs per individual varied according to the calling algorithm.
      Higher numbers of CNVs were detected in saliva than in blood DNA samples
      regardless of the algorithm used. All algorithms presented low agreement with
      mean Kappa Index (KI) <66. PennCNV was the most reliable algorithm (KI(w=) 98.96)
      when assessing the number of copies. The agreement observed in detecting CNV was
      higher in blood than in saliva samples. When comparing to MLPA, all algorithms
      identified poorly known copy aberrations (sensitivity = 0.19-0.28). In contrast,
      specificity was very high (0.97-0.99). Once a CNV was detected, the number of
      copies was truly assessed (sensitivity >0.62). Our results indicate that the
      current calling algorithms should be improved for high performance CNV analysis
      in genome-wide scans. Further refinement is required to assess CNVs as risk
      factors in complex diseases.

PMID- 21089070
TI  - Structural and biochemical consequences of NF1 associated nontruncating mutations
      in the Sec14-PH module of neurofibromin.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by alterations
      in the tumor suppressor gene NF1. Clinical manifestations include various neural
      crest derived tumors, pigmentation anomalies, bone deformations, and learning
      disabilities. NF1 encodes the Ras specific GTPase activating protein (RasGAP)
      neurofibromin, of which the central RasGAP related domain as well as a Sec14-like
      (residues 1560-1699) and a tightly interacting pleckstrin homology (PH)-like
      (1713-1818) domain are currently well defined. However, patient-derived
      nontruncating mutations have been reported along the whole NF1 gene, suggesting
      further essential protein functions. Focusing on the Sec14-PH module, we have
      engineered such nontruncating mutations and analyzed their implications on
      protein function and structure using lipid binding assays, CD spectroscopy and X
      ray crystallography. Although lipid binding appears to be preserved among most
      nontruncating mutants, we see major structural changes for two of the
      alterations. Judging from these changes and our biochemical data, we suggest the
      presence of an intermolecular contact surface in the lid-lock region of the
      protein.

PMID- 21089071
TI  - Legius syndrome in fourteen families.
AB  - Legius syndrome presents as an autosomal dominant condition characterized by cafe
      au-lait macules with or without freckling and sometimes a Noonan-like appearance
      and/or learning difficulties. It is caused by germline loss-of-function SPRED1
      mutations and is a member of the RAS-MAPK pathway syndromes. Most mutations
      result in a truncated protein and only a few inactivating missense mutations have
      been reported. Since only a limited number of patients has been reported up until
      now, the full clinical and mutational spectrum is still unknown. We report
      mutation data and clinical details in fourteen new families with Legius syndrome.
      Six novel germline mutations are described. The Trp31Cys mutation is a new
      pathogenic SPRED1 missense mutation. Clinical details in the 14 families
      confirmed the absence of neurofibromas, and Lisch nodules, and the absence of a
      high prevalence of central nervous system tumors. We report white matter T2
      hyperintensities on brain MRI scans in 2 patients and a potential association
      between postaxial polydactyly and Legius syndrome.

PMID- 21089073
TI  - Characterization of Pitx2c expression in the mouse heart using a reporter
      transgene.
AB  - To aid in detection and tracking of cells targeted by the left-right (LR) pathway
      in the heart throughout morphogenesis, expression from a Pitx2c-lacZ transgene
      (P2Ztg) was analysed in detail. beta-galactosidase expression from P2Ztg was
      robust, allowing reliable visualisation of low-level Pitx2c expression, and was
      virtually entirely dependent upon NODAL signalling in the heart. P2Ztg showed
      expression in trabecular and septal, as well as non-trabecular, myocardium, and a
      strong expression bias in myocardium associated with individual endocardial
      cushions of the atrioventricular canal and outflow tract, which are essential for
      cardiac septation. Expression on the ventral surface of the outflow tract evolved
      to a specific stripe that could be used to track the future aorta during outflow
      tract spiralling and remodelling. Our data show that the P2Ztg transgene is a
      useful resource for detection of molecular disturbances in the LR cascade, as
      well as morphogenetic defects associated with other cardiac congenital disorders.

PMID- 21089074
TI  - Three-dimensional localisation of NANOG, OCT4, and E-CADHERIN in porcine pre- and
      peri-implantation embryos.
AB  - The expression patterns of NANOG and OCT4 have previously been reported to differ
      markedly between mammalian species indicating distinct species-specific roles
      during development. We investigate the three-dimensional expression pattern of
      NANOG and OCT4 in porcine pre- and peri-implantation embryos. The expression of
      NANOG differed remarkably from that reported in other species. NANOG was not
      detected in the inner cell mass of hatched porcine blastocysts, but later
      appeared in the epiblast and hypoblast of spherical blastocysts where Rauber's
      layer had disintegrated. In pre-gastrulating, filamentous embryos NANOG was
      localised to nuclei in a minor portion of the epiblast cells in which E-CADHERIN
      seemed to be up-regulated and OCT4 down-regulated. Later NANOG was restricted to
      the potential PGCs. OCT4 was detected in inner cell mass, epiblast, and mesoderm,
      and we found that OCT4 expression, in contrast to earlier speculations, at least
      in hatched blastocysts, resembles the expression pattern in the mouse embryo.

PMID- 21089072
TI  - Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion
      development in mouse embryos.
AB  - Atrioventricular (AV) cushions are the precursors of AV septum and valves. In
      this study, we examined roles of Smad4 during AV cushion development using a
      conditional gene inactivation approach. We found that endothelial/endocardial
      inactivation of Smad4 led to the hypocellular AV cushion defect and that both
      reduced cell proliferation and increased apoptosis contributed to the defect.
      Expression of multiple genes critical for cushion development was down-regulated
      in mutant embryos. In collagen gel assays, the number of mesenchymal cells formed
      is significantly reduced in mutant AV explants compared to that in control
      explants, suggesting that the reduction of cushion mesenchyme formation in
      mutants is unlikely secondary to their gross vasculature abnormalities. Using a
      previously developed immortal endocardial cell line, we showed that Smad4 is
      required for BMP signaling- stimulated upregulation of Tbx20 and Gata4.
      Therefore, our data collectively support the cell-autonomous requirement of
      endocardial Smad4 in regulating AV cushion development.

PMID- 21089075
TI  - Migration of dorsal aorta mesenchymal stem cells induced by mouse embryonic
      circulation.
AB  - Mesenchymal stem cells (MSCs) represent powerful tools for regenerative medicine
      for their differentiation and migration capacity. However, ontogeny and migration
      of MSCs in mammalian mid-gestation conceptus is poorly understood. We identified
      canonical MSCs in the mouse embryonic day (E) 11.5 dorsal aorta (DA). They
      possessed homogenous immunophenotype (CD45(-)CD31(-)Flk-1(-)CD44(+)CD29(+)),
      expressed perivascular markers (alpha-SMA(+)NG2(+)PDGFRbeta(+)PDGFRalpha(+)), and
      had tri-lineage differentiation potential (osteoblasts, adipocytes, and
      chondrocytes). Of interest, MSCs were also detected in E12.5-E13.5 embryonic
      circulation, 24 hr later than in DA, suggesting migration like hematopoietic stem
      cells. Functionally, E12.5 embryonic blood could trigger efficient migration of
      DA-MSCs through platelet-derived growth factor (PDGF) receptor-, transforming
      growth factor-beta receptor-, but not basic fibroblast growth factor receptor
      mediated signaling. Moreover, downstream JNK and AKT signaling pathway played
      important roles in embryonic blood- or PDGF-mediated migration of DA-derived
      MSCs. Taken together, these results revealed that clonal MSCs developed in the
      mouse DA. More importantly, the embryonic circulation, in addition to its
      conventional transporting roles, could modulate migration of MSC during early
      embryogenesis.

PMID- 21089076
TI  - Distinct regulatory mechanisms control integrin adhesive processes during tissue
      morphogenesis.
AB  - Cell adhesion must be precisely regulated to enable both dynamic morphogenetic
      processes and the subsequent transition to stable tissue maintenance. Integrins
      link the intracellular cytoskeleton and extracellular matrix, relaying
      bidirectional signals across the plasma membrane. In vitro studies have
      demonstrated that multiple mechanisms control integrin-mediated adhesion;
      however, their roles during development are poorly understood. We used mutations
      that activate or deactivate specific functions of vertebrate beta-integrins in
      vitro to investigate how perturbing Drosophila betaPS-integrin regulation in
      developing embryos regulation affects tissue morphogenesis and maintenance. We
      found that morphogenetic processes use various beta-integrin regulatory
      mechanisms to differing degrees and that conformational changes associated with
      outside-in activation are essential for developmental integrin functions. Long
      term adhesion is also sensitive to integrin dysregulation, suggesting integrins
      must be continuously regulated to support stable tissue maintenance. Altogether,
      in vivo phenotypic analyses allowed us to identify the importance of various beta
      integrin regulatory mechanisms during different morphogenetic processes.

PMID- 21089077
TI  - ASSET: a robust algorithm for the automated segmentation and standardization of
      early Caenorhabditis elegans embryos.
AB  - The early Caenorhabditis elegans embryo is an attractive model to investigate
      evolutionarily conserved cellular mechanisms. However, there is a paucity of
      automated methods to gather quantitative information with subcellular precision
      in this system. We developed ASSET (Algorithm for the Segmentation and the
      Standardization of C. elegans Time-lapse recordings) to fill this need. ASSET
      automatically detects the eggshell and the cell cortex from DIC time-lapse
      recordings of live one-cell-stage embryos and can also track subcellular
      structures using fluorescent time-lapse microscopy. Importantly, ASSET
      standardizes the data into an absolute coordinate system to allow robust
      quantitative comparisons between embryos. We illustrate how ASSET can efficiently
      gather quantitative data on the motion of centrosomes and precisely track
      cortical invaginations, revealing hitherto unnoticed differences between wild
      type and saps-1(RNAi) embryos. In summary, we establish ASSET as a novel tool for
      the efficient quantification and standardization of images from early C. elegans
      embryos.

PMID- 21089081
TI  - Metal nanocrystals with highly branched morphologies.
AB  - Metal nanocrystals with highly branched morphologies are an exciting new class of
      nanomaterials owing to their unique structures, physicochemical properties, and
      great potential as catalysts, sensing materials, and building blocks for
      nanoscale devices. Various strategies have recently been developed for the
      solution-phase synthesis of metal nanocrystals with branched morphologies, such
      as multipods and nanodendrites. In this Minireview, the procedures and mechanisms
      underlying the formation of branched metal nanocrystals are presented in parallel
      with recent advances in synthetic approaches based on kinetically controlled
      overgrowth, aggregation-based growth, heterogeneous seeded growth, selective
      etching, and template-directed methods, as well as their properties for catalytic
      or electrocatalytic applications.

PMID- 21089082
TI  - Quantum-chemical and combined quantum-chemical/molecular-mechanical studies on
      the stabilization of a twin arginine pair in adenovirus Ad11.

PMID- 21089083
TI  - Modulating PNA/DNA hybridization by light.

PMID- 21089084
TI  - Gold-catalyzed oxidative ring expansions and ring cleavages of
      alkynylcyclopropanes by intermolecular reactions oxidized by diphenylsulfoxide.

PMID- 21089078
TI  - Developmental expression patterns of candidate cofactors for vertebrate six
      family transcription factors.
AB  - Six family transcription factors play important roles in craniofacial
      development. Their transcriptional activity can be modified by cofactor proteins.
      Two Six genes and one cofactor gene (Eya1) are involved in the human Branchio
      otic (BO) and Branchio-otic-renal (BOR) syndromes. However, mutations in Six and
      Eya genes only account for approximately half of these patients. To discover
      potential new causative genes, we searched the Xenopus genome for orthologues of
      Drosophila cofactor proteins that interact with the fly Six-related factor, SO.
      We identified 33 Xenopus genes with high sequence identity to 20 of the 25 fly SO
      interacting proteins. We provide the developmental expression patterns of the
      Xenopus orthologues for 11 of the fly genes, and demonstrate that all are
      expressed in developing craniofacial tissues with at least partial overlap with
      Six1/Six2. We speculate that these genes may function as Six-interacting partners
      with important roles in vertebrate craniofacial development and perhaps
      congenital syndromes.

PMID- 21089085
TI  - Murataite-pyrochlore series: a family of complex oxides with nanoscale pyrochlore
      clusters.

PMID- 21089087
TI  - Tetrakis(arylisocyanide) rhodium(I) salts in water: NIR luminescent and
      conductive supramolecular polymeric nanowires with hierarchical organization.

PMID- 21089086
TI  - The insatiable quest for near-infrared fluorescent probes for molecular imaging.

PMID- 21089092
TI  - Comment on processes for the direct conversion of cellulose or cellulosic biomass
      into levulinate esters.

PMID- 21089106
TI  - Marriage patterns in a Mesoamerican peasant community are biologically adaptive.
AB  - Differential investment in offspring by parental and progeny gender has been
      discussed and periodically analyzed for the past 80 years as an evolutionary
      adaptive strategy. Parental investment theory suggests that parents in poor
      condition have offspring in poor condition. Conversely, parents in good condition
      give rise to offspring in good condition. As formalized in the Trivers-Willard
      hypothesis (TWH), investment in daughters will be greater under poor conditions
      while sons receive greater parental investment under good conditions. Condition
      is ultimately equated to offspring reproductive fitness, with parents apparently
      using a strategy to maximize their genetic contribution to future generations.
      Analyses of sex ratio have been used to support parental investment theory and in
      many instances, though not all, results provide support for TWH. In the present
      investigation, economic strategies were analyzed in the context of offspring sex
      ratio and survival to reproductive age in a Zapotec-speaking community in the
      Valley of Oaxaca, southern Mexico. Growth status of children, adult stature, and
      agricultural resources were analyzed as proxies for parental and progeny
      condition in present and prior generations. Traditional marriage practice in
      Mesoamerican peasant communities is patrilocal postnuptial residence with
      investments largely favoring sons. The alternative, practiced by ~25% of parents,
      is matrilocal postnuptial residence which is an investment favoring daughters.
      Results indicated that sex ratio of offspring survival to reproductive age was
      related to economic strategy and differed significantly between the patrilocal
      and matrilocal strategies. Variance in sex ratio was affected by condition of
      parents and significant differences in survival to reproductive age were strongly
      associated with economic strategy. While the results strongly support TWH,
      further studies in traditional anthropological populations are needed.

PMID- 21089107
TI  - Investigation of diachronic dietary patterns on the islands of Ibiza and
      formentera, Spain: Evidence from carbon and nitrogen stable isotope ratio
      analysis.
AB  - To examine how dietary patterns may have changed in the western Mediterranean
      through time, stable carbon and nitrogen isotope ratios were measured on
      extracted bone collagen from fauna (n = 75) and humans (n = 135) spanning four
      distinct chronological periods: Chalcolithic (c.2100-1600 BC), Punic (6th-2nd/1st
      century BC), Late Antiquity-Early Byzantine (4th-7th century AD), and Islamic
      (c.10th-13th century AD) on the islands of Ibiza and Formentera, Spain. The
      Chalcolithic, Punic, and Late Antiquity-Byzantine societies all showed evidence
      of a predominately C(3) terrestrial-based diet with a possible input of a small
      amount of marine and/or C(4) dietary resources. In contrast, the Islamic
      population on Ibiza had a subsistence strategy that was reliant on a significant
      amount of C(4) plants and/or animals fed a C(4) diet, likely millet. These
      results indicate a fairly constant C(3) terrestrial-based diet on the islands of
      Ibiza and Formentera through time, with a shift to C(4) dietary resources during
      the Islamic Period. Further research is needed from other Islamic populations in
      and around the Mediterranean to better understand this unique dietary adaptation.
      Am J Phys Anthropol 143:512-522, 2010. (c) 2010 Wiley-Liss, Inc.

PMID- 21089108
TI  - Proceedings of the Seventy-Ninth Meeting of the American Association of Physical
      Anthropologists, the Hotel Albuquerque at Old Town, Albuquerque, New Mexico,
      April 9-12, 2010.

PMID- 21089109
TI  - Is calcium scoring of the coronary arteries necessary for proper management of
      asymptomatic subjects with classic risk factors?
AB  - In 2000, I wrote an editorial entitled, "Detecting Coronary Calcium."1 For the
      past several years there have been numerous publications on this subject.
      Recently, an article by Min et al, provided some important information about
      patients with a normal coronary calcium scan and the conversion from a zero
      calcium score to greater than zero.

PMID- 21089110
TI  - Hyponatremia in acute decompensated heart failure: mechanisms, prognosis, and
      treatment options.
AB  - Hyponatremia is common and is increasingly recognized as an independent
      prognostic marker that adversely affects morbidity and mortality in various
      disease states, including heart failure. In acute decompensated heart failure
      (ADHF), the degree of hyponatremia often parallels the severity of cardiac
      dysfunction and is further exacerbated by any reduction in glomerular filtration
      rate and arginine vasopressin dysregulation. A recent study showed that even
      modest improvement of hyponatremia may have survival benefits. Although
      management of hyponatremia in ADHF has traditionally focused on improving cardiac
      function and fluid restriction, the magnitude of improvement of serum sodium is
      fairly slow and unpredictable. In this article, we discuss the mechanisms of
      hyponatremia in ADHF, review its evolving prognostic significance, and evaluate
      the efficacy of various treatments for hyponatremia, including the recently
      approved vasopressin receptor antagonists for managing hyponatremia among
      patients hospitalized for ADHF.

PMID- 21089111
TI  - Alterations in corrected QT interval following liver transplant in patients with
      end-stage liver disease.
AB  - BACKGROUND: Studies have demonstrated that patients with end-stage liver disease
      (ESLD) often have a prolonged corrected QT interval (QTc) with variable changes
      in the QTc post-transplant. We sought to characterize the prevalence and degree
      of QTc prolongation in ESLD patients, identify risk factors for QTc prolongation,
      and assess changes in QTc following transplant. HYPOTHESIS: QTc interval is
      prolonged in ESLD patients pre-transplant due to a variety of risk factors and
      shortens following liver transplantation. METHODS: We conducted a retrospective,
      multicenter study utilizing 2 large liver-transplant databases. QTc intervals
      were calculated utilizing Bazett's formula. The cutoff used for prolonged QTc was
      440 milliseconds for men and 460 milliseconds for women. RESULTS: There were 269
      patients (169 men, 100 women) included in the final analysis. The mean pre
      transplant QTc was prolonged (449.0 ms), whereas the mean post-transplant QTc
      shortened and was within normal limits (416.7 ms) (P < 0.0001). QTc shortened
      after transplant in 87% of patients. QTc normalized in 70% of patients. Age and
      Model for End-Stage Liver Disease (MELD) score were not predictive of prolonged
      QTc at baseline. CONCLUSIONS: ESLD patients often have a prolonged QTc, which
      frequently shortens or normalizes after transplant. Screening for prolonged QTc
      is warranted if medications known to prolong the QTc interval are used in ESLD
      patients pre-transplant. MELD score, age, and sex were not predictive of
      prolonged QTc at baseline.

PMID- 21089112
TI  - Soluble receptors for advanced glycation end products (sRAGE) as a predictor of
      restenosis following percutaneous coronary intervention.
AB  - BACKGROUND: Interaction of advanced glycation end products (AGEs) with their
      receptor (RAGE) increases expression of inflammatory mediators (tumor necrosis
      factor alpha [TNF-alpha] and soluble vascular cell adhesion molecule-1 [sVCAM-1])
      and induces oxygen radicals that are implicated in atherosclerosis. Balloon
      injury-induced atherosclerosis is associated with increased expression of AGEs
      and RAGE. The soluble receptor for AGE (sRAGE), which acts as a decoy for RAGE
      ligands (AGEs), prevents atherosclerosis in this model. HYPOTHESIS: We evaluated:
      1) whether post-percutaneous coronary intervention (PCI) restenosis is associated
      with low pre-PCI serum sRAGE, high serum AGEs, TNF-alpha, and sVCAM-1, and high
      AGE/sRAGE ratio; 2) whether pre-PCI and post-PCI levels of these markers are
      similar in patients with or without restenosis; and 3) whether sRAGE and
      AGE/sRAGE ratio have predictive value for post-PCI restenosis. METHODS:
      Angiography was performed in 46 patients with non-ST-segment elevation myocardial
      infarction for assessment of restenosis. Serum sRAGE, AGEs, TNF-alpha, and sVCAM
      1 were measured in these patients and 20 control subjects. RESULTS: : Nineteen of
      the 46 patients developed post-PCI restenosis, which was associated with lower
      sRAGE and higher TNF-alpha and sVCAM-1 levels, and higher AGE/sRAGE ratio
      compared with patients without restenosis. Pre-PCI and post-PCI levels of these
      biomarkers were similar in both groups, except in patients with restenosis, in
      whom the post-PCI level of sRAGE was lower and TNF-alpha was higher than the pre
      PCI levels. The sensitivity and negative predictive value of sRAGE were 100%, and
      were higher than those of AGE/sRAGE ratio in identifying post-PCI restenosis.
      CONCLUSIONS: Both low serum sRAGE levels and high AGE/sRAGE ratio have predictive
      value for post-PCI restenosis.

PMID- 21089113
TI  - Long-term results following switch from abciximab to eptifibatide during
      percutaneous coronary intervention.
AB  - BACKGROUND: The usage of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors
      improves the outcome during high-risk percutaneous coronary interventions (PCI).
      The aim of this study was to evaluate the long-term effects after a planned
      switch from abciximab to eptifibatide during PCI. HYPOTHESIS: A switch from the
      general use of abciximab to eptifibatide as a GP IIb/IIIa in connection with PCI
      would not have any negative effects on long-term clinical outcomes. METHODS: To
      reduce costs, a general switch from abciximab to eptifibatide was instituted in
      2004 in 2 university hospitals in Sweden. All patients treated 6 months before
      and 6 months after the switch were followed for 30 months. During the study
      period, 1038 patients underwent PCI and received a GP IIb/IIIa receptor
      inhibitor, 481 (46%) before the switch (Group A) and 557 (54%) after the switch
      (Group B). The 2 groups had similar baseline characteristics. The primary
      endpoint was the composite of death, myocardial infarction, stroke, or new
      coronary revascularization (percutaneous or surgical); secondary endpoints were
      the individual components of this composite. A separate analysis was performed on
      patients treated for ST-segment elevation myocardial infarction, non-ST-segment
      elevation myocardial infarction/unstable angina, and diabetes, respectively. Data
      were collected from the Swedish Coronary Angiography and Angioplasty Registry.
      RESULTS: There were no differences between the groups in the primary endpoint
      (29.7% in Group A vs 29.3% in Group B; P = 0.48) or in any of the secondary
      endpoints. CONCLUSIONS: A switch from the general usage of abciximab to
      eptifibatide as a GP IIb/IIIa receptor inhibitor in connection with PCI did not
      seem to have any negative effects on long-term clinical outcomes.

PMID- 21089114
TI  - Cardiac shock wave therapy reduces angina and improves myocardial function in
      patients with refractory coronary artery disease.
AB  - BACKGROUND: Safe and effective therapeutic management of refractory coronary
      artery disease (CAD) in heart patients is critical to enhance cardiovascular
      function and improve quality of life. Current therapies for refractory CAD are
      inadequate in ameliorating angina and promoting revascularization of ischemic
      myocardium. HYPOTHESIS: Cardiac shock wave therapy (CSWT) is a safe and effective
      noninvasive intervention in the management of patients with refractory CAD.
      METHODS: The study enrolled 9 male patients age 50 to 70 years (5.11 +/- 5.46
      years) with a diagnosis of CAD and stent implantation (3.00 +/- 2.24 stents).
      CSWT was carried out for 3 months at 3 intervals during the first week of each
      month (first, third, and fifth day), for a total of 9 therapies per patient.
      Dobutamine stress echocardiography and radionuclide angiography identified the
      myocardial ischemic segments. The effects of CSWT on myocardial perfusion and
      systolic function were examined. Other outcome measures included myocardial
      injury enzyme markers, angina scale, nitroglycerin dosage, and cardiopulmonary
      fitness assessments. RESULTS: Improved myocardial blood flow and regional
      systolic function (stress peak systolic strain rate - 1.10 to - 1.60 s(-1), P =
      0.002) were detected in patients following CSWT. Reductions in creatine kinase
      (87.89 +/- 36.69 to 86.22 +/- 35.96 IU/L, P = 0.046), creatine kinase MB (10.89
      +/- 5.73 to 10.11 +/- 5.93 IU/L, P = 0.008), aspartate transaminase
      (interquartile range [IQR], 28.00 to 27.00 IU/L, P = 0.034) were also found.
      Angina (Canadian Cardiovascular Society scale IQR 3.0 to 2.0, P = 0.035) and
      nitroglycerin dose reduction (IQR 3.0 to 1.0 times/wk, P = 0.038) were reported.
      CONCLUSIONS: This study is a preliminary assessment of CSWT in patients with
      refractory CAD. We report that CSWT is a noninvasive, effective, and safe
      intervention in the treatment of refractory CAD.

PMID- 21089115
TI  - Prediction of long-term survival in chronic heart failure by multiple biomarker
      assessment: a 15-year prospective follow-up study.
AB  - BACKGROUND: In chronic heart failure (CHF), several plasma biomarkers identify
      subjects at risk of death over the midterm. However, their long-term predictive
      value in the context of other candidate predictors has never been assessed. This
      information may prove valuable in the management of a chronic disease with a long
      natural history, as CHF is today. HYPOTHESIS: We aimed to assess the very-long
      term prognostic power of a set of biomarkers to identify CHF patients at highest
      risk for all-cause mortality. METHODS: A group of 106 consecutive outpatients
      with CHF (85 male and 21 female, median age 56 y) was followed for 15 years.
      Echocardiographic tracings and blood samples were collected at study entry to
      evaluate cardiac function, plasma atrial natriuretic peptide (ANP), aldosterone,
      and erythropoietin, and plasma renin activity. The relationships between
      biomarkers, clinical and echocardiographic variables, and mortality were
      assessed. RESULTS: After 15 years, 86 of the 106 patients (81%) had died.
      Multivariate analysis showed that ANP was the best independent predictor of
      survival over several clinical, echocardiographic, and humoral variables (hazard
      ratio: 5.62, 95% confidence interval: 3.37-9.39, P < 0.001 for plasma levels <
      median value of 71 pg/mL). Plasma renin activity and erythropoietin provided
      prognostic information in univariate analysis, but lost their predictive power
      when adjusted for covariates. CONCLUSIONS: The present study represents the
      longest available follow-up of patients with CHF evaluating the prognostic power
      of multiple biomarkers. It shows that a simple assessment of plasma ANP levels is
      the strongest long-term predictor of death in all stages of heart failure.

PMID- 21089116
TI  - Higher C-reactive protein predicts worse prognosis in acute heart failure only in
      noninfected patients.
AB  - BACKGROUND: The prognostic role of C-reactive protein (CRP) in acute heart
      failure (HF) is not fully understood, and the impact of an infectious process in
      its risk-stratification power was not previously evaluated. HYPOTHESIS: As CRP is
      an inflammatory marker, its prognostic value in acute HF is probably different in
      patients with and without concurrent infection. METHODS: We recruited patients
      admitted to our hospital due to acute HF from October 2006 to October 2007. All
      patients were given treatment at the discretion of the attending physician. Serum
      CRP was measured at discharge in 225 patients. We followed patients for 3 months
      after discharge to assess occurrence of all-cause death or readmission due to HF.
      Infection was defined according to diagnoses registered on the discharge record.
      Patients were classified according to CRP tertiles, in the entire sample and in
      groups according to infection occurrence. RESULTS: : An infectious condition
      occurred in 109 patients (first and second CRP tertiles: 8.8 and 27.4 mg/L,
      respectively). No infection was detected in 116 patients (5.0 and 12.3 mg/L,
      respectively). In the group with infection, CRP was not a good predictor of
      adverse outcome. In the noninfected group, the hazard ratio of those with CRP >
      12.3 mg/L was 2.46 (95% confidence interval: 1.29-4.70) in comparison with those
      with lower CRP. Adjusted hazard ratio for ischemic heart disease and diabetes was
      2.03 (95% confidence interval: 1.06-3.91). CONCLUSIONS: CRP had no prognostic
      value in acute HF patients with an infectious complication. Noninfected patients
      with higher CRP at discharge had worse prognosis.

PMID- 21089117
TI  - Preimplant left ventricular end-diastolic dimension and body weight independently
      associate with paced QRS duration in patients receiving right ventricular apical
      pacing for complete atrioventricular block.
AB  - BACKGROUND: Paced QRS duration, a good marker of ventricular asynchrony while
      pacing, has been accepted as a valuable predictor of new-onset heart failure in
      patients receiving right ventricular apical pacing. But nowadays we have little
      evidence for predicting paced QRS duration before the implantation. HYPOTHESIS:
      There might be relationships between paced QRS duration and demographic
      characteristics, clinical features such as comorbidities, native QRS duration, or
      preimplant cardiac size. The purpose of this article was to identify potential
      predictors of paced QRS duration in patients receiving right ventricular apical
      pacing for complete atrioventricular block. METHODS: One hundred seventy patients
      with right ventricular apical pacing for complete atrioventricular block were
      divided into 2 groups according to whether the paced QRS duration was longer than
      170 ms or not. Demographic characteristics, clinical features, electrocardiogram
      and echocardiography before implantation, and electrocardiogram immediately after
      implantation, were retrospectively recorded. RESULTS: Preimplant left ventricular
      end-diastolic dimension (LVEDD) and body weight were found to be independently
      associated with the paced QRS duration. Although both of them had low sensitivity
      and specificity in predicting paced QRS duration longer than 170 ms, the
      specificity could increase to 81.2% when they were combined. CONCLUSIONS: Both
      preimplant LVEDD and body weight independently associate with paced QRS duration
      in patients receiving apical pacing for complete atrioventricular block. Although
      whether they really have an effect on new-onset heart failure still needs to be
      verified, and these findings might be a good indication.

PMID- 21089118
TI  - Adenomatous polyposis coli is essential for both neuronal differentiation and
      maintenance of adult neural stem cells in subventricular zone and hippocampus.
AB  - The tumor suppressor adenomatous polyposis coli (APC) is a multifunctional
      protein that not only inhibits the Wnt signaling pathway by promoting the
      degradation of beta-catenin but also controls cell polarity, motility, and
      division. APC is abundantly expressed in the adult central nervous system, but
      its role in adult neurogenesis remains unknown. Using conditional deletion (or
      knockout) of APC (APC-CKO) from glial fibrillary acidic protein (GFAP)-expressing
      cells including adult neural stem cells (NSCs) in the subventricular zone and
      hippocampal dentate gyrus, we show that APC expression by these cells is a
      critical component of adult neurogenesis. Loss of APC function resulted in a
      marked reduction of GFAP-expressing NSC-derived new neurons, leading to the
      decreased volume of olfactory granule cell layer. Two distinct mechanisms account
      for impaired neurogenesis in APC-CKO mice. First, APC was highly expressed in
      migrating neuroblasts and APC deletion disturbed the differentiation from Mash1
      expressing transient amplifying cells to neuroblasts with concomitant
      accumulation of beta-catenin. As a result, migrating neuroblasts decreased,
      whereas Mash1-expressing dividing cells reciprocally increased in the olfactory
      bulb of APC-CKO mice. Second, APC deletion promoted an exhaustion of the adult
      germinal zone. Functional NSCs and their progeny progressively depleted with age.
      These findings demonstrate that APC expression plays a key role in regulating
      intracellular beta-catenin level and neuronal differentiation of newly generated
      cells, as well as maintaining NSCs in the adult neurogenic niche. STEM CELLS
      2010;28:2053-2064.

PMID- 21089119
TI  - Concise review: stem cells as an emerging platform for antibody therapy of
      cancer.
AB  - Monoclonal antibodies are important tools for cancer therapy, however, three
      factors limit their effectiveness: toxicity, poor tumor penetration, and
      inability to cross the blood-brain barrier. This review discusses the emerging
      field of stem cell-mediated antibody delivery and how this approach may improve
      antibody therapy of cancer by overcoming these obstacles.

PMID- 21089127
TI  - What are the cut-off levels for IL-6 and CRP in neonatal sepsis?
AB  - Neonatal sepsis, characterized by systemic signs of infection in the first month
      of life, remains an important clinical syndrome. Despite advances in neonatology,
      it has high rates of mortality and morbidity. The combine or alone usage of
      interleukin-6 (IL-6) and C-reactive protein (CRP) has recently been proven to be
      useful in the early diagnosis of sepsis in newborns. The study included 282
      patients; there were 232 in Group I (170 proven and 62 clinical sepsis) and 50 in
      Group II (control group). The optimum cut-off value in the diagnosis of neonatal
      sepsis was found to be 24.65 pg/ml for IL-6 and 4.82 mg/l for CRP. Sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of this IL-6 cut-off for neonatal sepsis were 72, 84, 95, and 42%, respectively.
      Sensitivity, specificity, PPV, and NPV of the CRP cut-off for neonatal sepsis
      were 67, 97, 99, and 39%, respectively. The combination of IL-6 (>24.65 pg/ml)
      and CRP (>4.82 mg/l) in the diagnosis of neonatal sepsis gave sensitivity,
      specificity, PPV, and NPV of 53, 100, 100, and 33%, respectively. To our
      knowledge, this is the largest reported study seeking to determine cut-off levels
      for IL-6 and CRP in the diagnosis of neonatal sepsis. In conclusion, we think
      that it is useful to evaluate IL-6 and CRP, in combination, for the early
      diagnosis of neonatal sepsis.

PMID- 21089143
TI  - Decision making in head and neck cancer care.
AB  - OBJECTIVES/HYPOTHESIS: To describe patterns of patient involvement in head and
      neck cancer decision making. STUDY DESIGN: Prospective longitudinal ethnography
      of otolaryngology patients making treatment decisions. METHODS: Grounded theory
      analysis of verbatim transcripts and original voice recordings from: 1)
      participant-driven diaries, 2) participants' office visits with their physicians,
      and 3) semistructured interviews completed after a treatment decision had been
      made. RESULTS: Patients with serious illness and experiencing considerable pain,
      discomfort, or alteration in the ability to perform activities of daily living,
      and who fear for their life, do not make decisions in a way that adheres to the
      conventional model of decision making, which presumes a sequential, office-based
      interaction with clear patient autonomy. These patients have the ability to
      interpret information they receive during office visits, but they describe making
      a treatment decision as "deciding to do something" not choosing a specific
      treatment. This group also describes "trust" or "confidence" in the physician as
      the most important factor in making a decision, not the type or amount of
      information received. They move through providers toward treatment in a linear
      fashion, from one physician specialty to the next, usually without doubling back
      to revisit previous decisions or discussions. CONCLUSIONS: Decision making in
      serious illness unfolds differently than in less serious problems. The
      conventional model does not fit this patient population, and reliance on trust of
      the physician figures prominently. Decision support should be aimed at physician
      decision making, promoting explicit incorporation of patient-specific data into
      the process.

PMID- 21089144
TI  - Vimentin intermediate filaments: the central base in sinus endothelial cells of
      the rat spleen.
AB  - The ultrastructural distribution of vimentin intermediate filaments (IFs) and
      localizations of the related proteins in sinus endothelial cells of the rat
      spleen was examined by confocal laser scanning and electron microscopy with
      detergent extraction, myosin-fragment 1 decoration, and immunogold labeling to
      elucidate their functions in endothelial cells. Vimentin IFs were extremely
      abundant over stress fibers in the basal part of the endothelial cells. Some of
      them were intermingled with actin filaments in stress fibers, and were associated
      with coated vesicles. Plectin was predominantly localized in the layers of
      vimentin and stress fibers of the endothelial cells, but rarely in the vicinity
      of adherens junctions in the lateral part and focal adhesions in the basal part
      of the cells. Neither plakoglobin nor desmoplakin, which is coupled VE-cadherin
      to vimentin IFs, was detected in sinus endothelial cells. Vinculin was localized
      in the basal membranes of the endothelial cells. These data suggest that abundant
      vimentin IFs are associated with stress fibers by plectin in the basal part of
      the cells and form cytoskeletal cores of sinus endothelial cells only partially
      supported by the ring-shaped basal lamina to have roles in scaffolding and the
      mechanical stabilization of the endothelial cells. Furthermore, taken in
      connection with recently revealed functions of vimentin and plectin, vimentin
      might play a cytoskeletal core of sinus endothelial cells.

PMID- 21089156
TI  - Impact of gavage dosing procedure and gastric content on adverse respiratory
      effects and mortality in rat toxicity studies.
AB  - Unscheduled mortality preceded by adverse respiratory clinical signs in rats
      dosed by oral gavage may not only be caused by technical gavage error or systemic
      toxicity but may also be caused by gastro-esophageal reflux and subsequent
      aspiration of high concentrations of drug formulation. In a 3 week oral gavage
      rat toxicity study for an early drug development compound, preterminal deaths
      (approximately 20% of animals) at high doses (>=1000 mg kg(-1) ) and
      concentrations (>=60 mg ml(-1) ) were preceded by recurrent dyspnea, rales or
      excessive salivation, without evidence of accidental intrapulmonary gavage error.
      Histological evaluation revealed extensive necrosis and inflammatory changes in
      the upper respiratory tract, especially in the nasal turbinates and/or
      nasopharynx. The presence of food particles in inflammatory exudates suggested a
      retrograde aspiration of stomach content with test formulation via the
      nasopharyngeal duct into the posterior region of the nose. In contrast, no
      mortality or adverse respiratory effects were observed in rats following 2 week
      intravenous administration at comparable exposures or oral gavage administration
      at lower concentrations (<=20 mg ml(-1) ). In a pharmacology study, the compound
      caused a dose-dependent increase in gastric content (partly due to inhibition of
      gastric emptying), providing a pharmacological basis for the suspected gavage
      mediated gastroesophageal reflux. Reducing the dose volume and dosing fasted
      animals substantially reduced or eliminated the respiratory effects and mortality
      at the high test article concentrations, demonstrating that the adverse effects
      are related to the gavage method.

PMID- 21089157
TI  - Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA
      damage and carcinogenesis in female Balb/C mice.
AB  - This study investigated the protective effect of oral treatment with lemongrass
      (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced
      by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was
      investigated in a multi-organ carcinogenesis bioassay induced by 7,12
      dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4
      hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In
      the short-term study, the animals were allocated into three groups: vehicle group
      (negative control), MNU group (positive control) and LGEO 500 mg kg-1 (five times
      per week for 5 weeks) plus MNU group (test group). Blood samples were collected
      to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at
      the end of weeks 3 and 5. The LGEO 500 mg kg-1 treated group showed significantly
      lower (P < 0.01) leukocyte DNA damage than its respective positive group exposed
      to MNU alone at week 3. In the medium-term study, DDB-initiated mice were
      allocated into three groups: vehicle group (positive control) and LGEO 125 or 500
      mg kg-1 (five times per week for 6 weeks; test groups). At week 20, all animals
      were euthanized and mammary glands, colon and urinary bladder were processed for
      histopathological analyses for detection of preneoplastic and neoplastic lesions.
      A slight non-significant effect of treatment with LGEO 500 mg kg-1 in reducing
      development of alveolar and ductal mammary hyperplasia was found (P = 0.075). Our
      findings indicate that lemongrass essential oil provided protective action
      against MNU-induced DNA damage and a potential anticarcinogenic activity against
      mammary carcinogenesis in DDB-initiated female Balb/C mice.

PMID- 21089158
TI  - Biocompatible gellan gum-reduced gold nanoparticles: cellular uptake and subacute
      oral toxicity studies.
AB  - Currently gold nanoparticles are being explored for drug delivery and other
      biomedical applications; therefore it is necessary to study the fate of such
      nanoparticles inside the body. The objective of the present study was to
      investigate the cellular uptake and toxicity of the gold nanoparticles
      synthesized using a microbial polysaccharide, gellan gum, as a capping and
      reducing agent. The cellular uptake of gold nanoparticles was studied on mouse
      embryonic fibroblast cells, NIH3T3 and human glioma cell line, LN-229. The
      cellular uptake study indicated that the gellan gum-reduced gold nanoparticles
      were located in cancer cells (LN-229) while no uptake was observed in normal
      mouse embryonic fibroblast cells (NIH3T3). The toxicity of the gold nanoparticles
      was evaluated by carrying out subacute 28 day oral toxicity studies in rats.
      Subacute administration of gum-reduced gold nanoparticles to the rats did not
      show any hematological or biochemical abnormalities. The weight and normal
      architecture of various organs did not change compared with control. The current
      findings, while establishing the specific uptake of nanoparticles into cancerous
      cells, also demonstrates that the gellan gum-reduced gold nanoparticles are
      devoid of toxicity in animals following oral administration.

PMID- 21089159
TI  - Studies on the toxic effects of microcystin-LR on the zebrafish (Danio rerio)
      under different temperatures.
AB  - It is well known that fish have stronger tolerance than mammals to microcystin
      (MC) exposure, and such a difference is attributed to their different core body
      temperatures. However, no in vivo study has been conducted to investigate the
      effects of temperature on MC-induced toxicity in fish, a typical poikilotherm.
      Tolerance and detoxification response of zebrafish treated with MC-LR were
      investigated under three temperatures. The LD50 values evidently increased with a
      decline of the temperature (547, 260 and 176 ug kg-1 at 12, 22 and 32  degrees C,
      respectively), indicating stronger tolerance of the fish at lower temperatures.
      Changes in the transcription of glutathione S-transferase (GST) isoforms in the
      fish were observed, and their sensitivity of response in the transcription of GST
      mRNA was on the order of 12 > 32 > 22 degrees C. We screened out several GST
      genes which were more delicate to solve the MC-LR exposure at different
      temperatures, i.e. GST rho1, al, p1 and theta1 in the 12  degrees C group, and
      GST zeta1 and p2 in the 22 and 32  degrees C groups. Our findings partly validate
      the hypothesis that high temperature enhances toxic effects of MCs on
      poikilotherms. Our studies also indicate that temperature-dependent toxic effects
      should be taken into account for field toxic assessment of microcystins in fish.

PMID- 21089160
TI  - Different reaction patterns of dopamine content to prenatal exposure to
      chlorpyrifos in different periods.
AB  - Developmental exposure to chlorpyrifos (CPF) induces abnormalities in
      neurotransmission. In the present study, we evaluated the dopamine reaction
      patterns in brain regions after CPF exposure during different prenatal periods.
      Animals were exposed on gestational days (GD) 7.5-11.5 or 13-17 and assessed at
      GD17, and at postnatal days (PN) 14 and 60. CPF exposure during GD7.5-11.5
      elicited a decrease in dopamine content at each measurement stages, with more
      changes in the hippocampus than in the cerebral cortex. In contrast, CPF exposure
      in GD13-17 elicited a decrease in dopamine content at PN14 and PN60, with more
      changes in the cerebral cortex than in the hippocampus. These results suggest
      that the two key brain regions involved in learning and memory, the cerebral
      cortex and hippocampus, react differently to CPF exposure in different prenatal
      periods. The abnormalities did not recover long after cessation of CPF exposure
      and deficiencies persisted into pre-puberty and adulthood.

PMID- 21089161
TI  - NADPH oxidase participates in the oxidative damage caused by fluoride in rat
      spermatozoa. Protective role of alpha-tocopherol.
AB  - Fluorosis, caused by drinking water contaminated with inorganic fluoride, is a
      public health problem in many areas around the world. The aim of this study was
      to evaluate oxidative stress in spermatozoa caused by fluoride and NADPH oxidase
      in relationship to fluoride. Four experimental groups of male Wistar rats were
      administered with deionized water, NaF, at a dose equivalent to 5 mg fluoride kg
      1 per 24 h, NaF plus 20 mg kg-1 per 24 h alpha-tocopherol, or alpha-tocopherol
      alone for 60 days. We evaluated several spermatozoa parameters in the four
      groups: standard quality analysis, superoxide dismutase (SOD) activity, the
      generation of reactive oxygen species (ROS), NADPH oxidase activity, TBARS
      formation, ultrastructural analyses of spermatozoa using transmission electron
      microscopy and in vitro fertilization (IVF) capacity. After 60 days of treatment,
      urinary excretion of fluoride was not modified by alpha-tocopherol. Spermatozoa
      from fluoride-treated rats exhibited a significant increase in the generation of
      ROS, accompanied by a significant increase in NADPH oxidase activity. The
      increase in ROS generation was significantly diminished by diphenylene iodonium,
      an inhibitor of NADPH oxidase activity. In contrast, a decrease in the generation
      of ROS, an increase in SOD activity and the prevention of TBARS formation process
      were observed in spermatozoa of rats exposed to fluoride plus alpha-tocopherol.
      Finally, alpha-tocopherol treatment prevented the IVF incapacity observed in the
      spermatozoa from fluoride-treated rats. These results suggest that NADPH oxidase
      participates in the oxidative stress damage caused by subchronic exposure to
      fluoride.

PMID- 21089162
TI  - Application of dosimetry systems and cytogenetic status of the child population
      exposed to diagnostic X-rays by use of the cytokinesis-block micronucleus cytome
      assay.
AB  - Low-dose ionizing radiation used for medical purposes is one of the definite risk
      factors for cancer development, and children exposed to ionizing radiation are at
      a relatively greater cancer risk as they have more rapidly dividing cells than
      adults and have longer life expectancy. Since cytokinesis-block micronucleus
      cytome (CBMN Cyt) assay has become one of the standard endpoints for radiation
      biological dosimetry, we used that assay in the present work for the assessment
      of different types of chromosomal damage in children exposed to diagnostic X-ray
      procedures. Twenty children all with pulmonary diseases between the ages of 4 and
      14 years (11.30 +/- 2.74) were evaluated. Absorbed dose measurements were
      conducted for posterior-anterior projection on the forehead, thyroid gland,
      gonads, chest and back. Doses were measured using thermoluminescence and
      radiophotoluminescent dosimetry systems. It was shown that, after diagnostic X
      rays, the mean total number of CBMN Cyt assay parameters (micronucleus,
      nucleoplasmic bridges and nuclear buds) was significantly higher than prior to
      diagnostic procedure and that interindividual differences existed for each
      monitored child. For the nuclear division index counted prior and after
      examination, no significant differences were noted among mean group values. These
      data suggest that even low-dose diagnostic X-ray exposure may induce damaging
      effect in the somatic DNA of exposed children, indicating that immense care
      should be given in both minimizing and optimizing radiation exposure to diminish
      the radiation burden, especially in the youngest population.

PMID- 21089163
TI  - Long-term feeding effects of stevioside sweetener on some toxicological
      parameters of growing male rats.
AB  - Several attempts to decrease sugar demand by introducing stevioside as a sugar
      substitute in children's food products have been made, but safety issues were
      concerned. This exploratory study investigated the effects of stevioside low dose
      (SL), high dose (SH) and low dose with inulin (SL + I) for 12 weeks on the body
      weight, organ relative weight, hematological and biochemical parameters and
      enzyme activities of young male rats. The SL dose used in this study was 15 mg
      kg(-1) per day and the SH dose was 100-fold the low dose. Enormous similarities
      in most parameters were observed with no significant differences between SL, SL +
      I and control except in the lipid profile. Total lipid reduction in SL and SL + I
      and significant high-density lipoprotein increase in SL + I were observed, which
      may be considered as clinically beneficial. Significant decreases in serum
      tartrate-resistant acid phosphatase activity were also observed in all
      treatments. Treatment with SH caused significant changes in all investigated
      toxicological parameters. The results indicated that, although the SL dose was
      higher than the stevioside temporary accepted daily intake (5.0 mg kg(-1) body
      weight), no toxicological effects were observed in SL or SL + I on body weight,
      organ relative weight, hematological and biochemical parameters or enzyme
      activities investigated in this study, whereas stevioside high dose (1500 mg kg(
      1) per day) may be considered as a toxic dose for the same biological parameters
      in young male rats. However, the effects of SL, SH and SL + I on serum tartrate
      resistant acid phosphatase activity need more investigation.

PMID- 21089164
TI  - In vivo genotoxicity assessment of nerolidol.
AB  - Nerolidol is a sesquiterpenoid component of essential oil used as a flavor and
      aroma enhancer. It has also been studied as a topical skin penetration enhancer,
      and has inhibitory activities against S. aureus and E. coli, among other
      activities. The objective of this study was to evaluate the ability of a single
      nerolidol treatment to induce DNA damage in peripheral blood and liver cells of
      mice and micronuclei in polychromatic erythrocytes of bone marrow cells of the
      same animals. In the dose range-finding assays, the maximum tolerated dose was
      higher than 2000 mg kg(-1) . The doses used in the experiments were 250, 500 and
      2000 mg kg(-1) , administered by gavage in a single dose. Peripheral blood cells
      were collected 4 and 24 h after the treatments and liver cells 24 h after. At
      least 100 nucleoids per cell type/animal were analyzed to determine the DNA
      damage scores and 2000 PCEs per animal for micronuclei in PCEs. The positive
      control was N-nitroso-N-ethylurea 50 mg kg(-1) . Cytotoxicity was assessed by
      scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE)
      erythrocytes (PCE:NCE ratio). The results showed that nerolidol induced weak
      levels of dose-related DNA damage in both types of cells analyzed, and enhanced
      the average number of micronucleated cells in the two high doses tested. The
      PCE:NCE ratio showed no cytotoxicity for the three doses of the compound. The
      data obtained support the view that nerolidol induces clastogenicity and very
      weak genotoxicity in the mouse cells tested.

PMID- 21089165
TI  - Predictive values of neutrophil CD64 expression compared with interleukin-6 and C
      reactive protein in early diagnosis of neonatal sepsis.
AB  - BACKGROUND: Despite major advances in the management of newborn infants, neonatal
      sepsis (NS) remain important causes of neonatal morbidity and mortality in the
      newborn, mainly among preterm and low birth weight infants. OBJECTIVE: The aim of
      this study was to investigate the usefulness of neutrophil CD64 expression alone
      and together with other infection markers in NS. METHODS: Peripheral blood
      samples were taken from 109 neonates, who were categorized into three groups:
      proven or clinical sepsis (n=35); disease without infection (n=42); and healthy
      controls (n=32). Complete blood count with differential, interleukin-6 (IL-6), C
      reactive protein (CRP), and cell surface expression of CD64 on neutrophils have
      been evaluated in a prospective manner as a diagnostic aid for NS. RESULTS:
      Expression of CD64 was significantly enhanced in neonates with sepsis compared
      with newborns with disease without infection and healthy controls (P=0.001 and
      P=0.001, respectively). Cutoff values of IL-6, CRP, CD64(MFI), and CD64(i) were
      24.9  pg/ml, 4.05  mg/l, 87.7, and 4.39, respectively. Sensitivity-negative
      predictive values of IL-6, CRP, and CD64(MFI)/CD64(i) were 80.0-90.6%, 80.0
      88.8%, and 88.6-94.0%, respectively. Combining all three tests increased the
      sensitivity to 100%; however, specificity and positive predictive value decreased
      to 62.1 and 55.5%, respectively. CONCLUSIONS: CD64 might be used either alone or
      combined with IL-6 and CRP for early diagnosis of NS. The advantages of CD64 when
      compared with IL-6 and CRP are rapid quantitation, very small blood volume
      required, and easy handling.

PMID- 21089166
TI  - Rs 6313 polymorphism in 5-hydroxytryptamine receptor 2A gene association with
      polysymptomatic primary nocturnal enuresis.
AB  - BACKGROUND: Tricyclic antidepressants (TCA) were used to treat nocturnal enuresis
      (NE) for decades of years although their real mechanisms are unknown. Recently,
      some case studies demonstrated the efficacy of selective serotonin reuptake
      inhibitors (SSRI) in the treatment of NE. Both TCA and SSRI have similar
      influences on serotonin transmission. This study was aimed at evaluating whether
      5-hydroxytryptamine receptor 2A (5HTR2A) gene is associated with NE. METHODS: We
      analyzed rs6313 polymorphism in 5HTR2A gene of 213 Taiwanese children (116 NE
      cases and 97 healthy control subjects) using polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: There were no significant
      differences when comparing the genotypes and allelic frequencies of rs6313
      polymorphism in 5HTR2A gene between patients with NE and control subjects.
      However, when subsequently comparing 5HTR2A genotypes and allelic frequencies in
      NE child with different phenotypes, genotypes TT and TC appeared higher risks of
      polysymptomatic NE compared with CC (odds ratio (OR)=10.71, 95% confidence
      interval (CI)=2.66-43.12; OR=2.68, 95% CI=0.67-10.75, respectively; P=0.0002);
      and allele T also revealed higher frequencies of polysymptomatic NE compared with
      allele C (OR=3.7, 95% CI=2.01-6.79, P=0.000015). CONCLUSIONS: This is the first
      study that shows the association between 5HTR2A gene polymorphisms and
      polysymptomatic NE. These results provide further evidence suggesting that
      genetic variations at 5HTR2A may influence NE treatment response.

PMID- 21089167
TI  - Role of tissue disorder markers in the evaluation of disease progress and outcome
      prediction: a prospective cohort study in non-cardiac critically ill patients.
AB  - BACKGROUND: Acute Physiology and Chronic Health Evaluation (APACHE) has a
      remarkable association with clinical syndrome, life expectancy, and length of
      ward stay. But the defects are obvious. It is crucial to detect an effective and
      convenient evaluation method to monitor disease progress and predict outcome.
      OBJECTIVE: To determine whether myoglobin (Mb) and other five tissue disorder
      biomarkers, troponin-I, creatine-kinase, creatine kinase-muscle brain, aspartate
      aminotransferase, and lactate dehydrogenase are independent predictors of disease
      progress and mortality in non-cardiac critical illness. METHODS: A prospective
      study with 179 patients admitted to the Intensive Care Unit was conducted. All
      serum tissue disorder markers and APACHE-II score were measured within 24  hr of
      admission. RESULTS: All the six biomarkers were significantly correlated with
      disease severity stratified by APACHE-II and outcome. Serial blood samples were
      taken from 17 patients on detection of two new organs failure. The occurrence of
      organs failure was significantly associated with the elevation of Mb, troponin-I,
      and APACHE-II. Multivariate analysis demonstrated that elevated Mb was the
      principal risk factor related to mortality either during hospitalization or 180
      day followup. Kaplan-Meier method and log-rank test also showed that patients
      with elevated Mb levels had significantly shorter survival. The mortality was
      higher in patients with both Mb>500  ng/ml and APACHE-II>20 than in those with
      only Mb>500  ng/ml or APACHE-II>20. CONCLUSION: All the six tissue disorder
      markers are predictors of disease severity, organ failure, and outcome in non
      cardiac critically illness. Among them, Mb plays a pivotable role. The combined
      use of Mb and APACHE-II suggest an effective method to determine the outcome of
      critical ill syndrome.

PMID- 21089168
TI  - Platelet count and erythrocyte sedimentation rate are good predictors of Kawasaki
      disease: ROC analysis.
AB  - BACKGROUND AND AIMS: Kawasaki disease (KD) is the leading cause of acquired
      pediatric cardiac disease and requires a timely diagnosis. Available effective
      therapy is ideally administered within 10 days of illness diagnosis. Recent
      reports of several laboratory tests in KD have been published. In this study, we
      aimed to evaluate the sensitivity and specificity of several laboratory tests.
      METHODS: We performed a retrospective study of consecutive patients diagnosed
      with KD from January to December 2008. We studied the sensitivity and specificity
      of several different tests [T-cell subgroups, platelet count, erythrocyte
      sedimentation rate (ESR), and C-reactive protein (CRP)] to predict KD using
      receiver operator characteristic curve analysis. RESULTS: No significant
      difference was demonstrated in T-cell subgroups between patients with KD and
      referent patients (P>0.05). However, platelet count, ESR, and CRP were
      significantly higher in patients with KD than in referent patients (P<0.05). ESR
      showed a sensitivity of 93.9% and specificity of 83.3% with a cut-off of 15 
      mm/hr (area under the curve [AUC], 89.1%; P=0.03). Platelet count showed a
      sensitivity of 70.6% and specificity of 75% with a cut-off of 336.5*10(9)/l (AUC,
      71.2%; P=0.03). CONCLUSIONS: These results indicate that platelet count and ESR
      are good predictors of KD.

PMID- 21089169
TI  - Alterations in biomarkers of endothelial function following on-pump coronary
      artery revascularization.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) has been associated with activation and
      injury of endothelial cells, probably responsible for the systemic inflammatory
      response syndrome (SIRS) taking place in these patients. METHODS: We measured
      plasma concentrations of soluble P-selectin (sP-s), E-selectin (sE-s),
      tetranectin (TN), vonWillebrand factor (vWF) levels, and angiotensin-converting
      enzyme (ACE) activity in 31 adult patients undergoing elective coronary artery
      bypass grafting, just before and up to three days after surgery, and in 25
      healthy volunteers. RESULTS: Patients showed higher plasma sP-s and sE-s and ACE
      concentrations, just before surgery, but significantly lower TN levels, compared
      with controls. During the first three postoperative days (PD), the concentration
      of each of the molecules followed a different and independent pattern, although
      in the third PD, the levels of sP-s, sE-s and ACE were higher and those of vWF
      and TN lower, compared with the preoperative ones. However, patients had higher
      sP-s (P=0.06), sE-s (P=0.07), and vWF (P=0.005), but lower TN concentrations
      (P=0.02) on the third PD compared with controls. CONCLUSIONS: CPB is
      characterised by pronounced changes in plasma sP-s, sE-s, TN, vWF levels, and ACE
      activity, which are associated with significant alteration in the intra- and
      early postoperative endothelial function observed in open heart surgery.

PMID- 21089170
TI  - Ischemia-modified albumin in acute aortic dissection.
AB  - BACKGROUND: Acute aortic dissection (AOD) is associated with high mortality and
      early diagnosis and treatment are essential. Ischemia-modified albumin (IMA) is a
      marker of myocardial ischemia whereas cardiac enzymes are released when
      myocardial necrosis occurs. We investigated, for the first time, whether IMA
      increases in AOD either at presentation or after surgery. METHODS: We studied 46
      consecutive patients with documented AOD; we also evaluated 13 consecutive
      patients with dilated ascending aortas scheduled for elective surgery and
      admitted for preoperative coronary angiography; 46 age-matched normal subjects
      served as controls. Only patients with acute onset of symptoms were included. We
      evaluated IMA, cardiac enzymes, N-terminal pro-B-type natriuretic peptide,
      albumin, C-reactive protein (CRP), and D-dimers on admission, 24  hr post
      operatively and 4 days post-operatively. Duration from symptom onset to the first
      sample was 23+/-17  hr. RESULTS: IMA did not differ between patients with AOD at
      presentation (93+/-19  U/ml), patients with chronic aneurysms (90+/-14  U/ml) and
      normal controls (91+/-9  U/ml). In addition, IMA did not change significantly
      after surgical repair. IMA, at baseline, however, correlated positively with time
      from symptom onset as well as CRP levels (P=0.05 and P=0.007, respectively).
      CONCLUSION: IMA is not elevated in AOD when blood sampling is performed within
      23+/-17  hr after symptom onset nor increases after surgery.

PMID- 21089171
TI  - Preliminary evaluation of Hitchens-Pike-Todd-Hewitt medium (HPTH) for detection
      of Group B Streptococci in pregnant women.
AB  - We aimed to compare Hitchens-Pike-Todd-Hewitt (HPTH) enrichment broth, Todd
      Hewitt broth, and direct culture onto blood sheep agar containing selective
      antimicrobial (ABA) in screening Group B Streptococci (GBS) carriage in pregnant
      women. From April to June 2007, duplicate lower vaginal and duplicate anorectal
      specimens of 102 pregnant women at 35 weeks of gestation or more, who were
      assisted at Santa Casa de Misericordia Hospital, Maringa, Parana, Brazil, were
      screened by GBS using HPTH, Todd-Hewitt broth, and ABA. Twenty-five (24.5%)
      pregnant women had one or more positive culture for GBS in those media. The
      positive rate for each medium was 21.6% (22/102) in the HPTH, 12.8% (13/102) in
      ABA, and 11.8% (12/102) in Todd-Hewitt broth. HPTH seems to be a high
      satisfactory medium for screening GBS in vaginal and anorectal samples in
      pregnant women and additional studies would be interesting in a larger number of
      pregnant women and in different laboratories.

PMID- 21089173
TI  - Effect of spironolactone, potassium canrenoate, and their common metabolite
      canrenone on Dimension Vista Digoxin Assay.
AB  - Spironolactone, a potassium sparing diuretic metabolized to canrenone, is often
      used with digoxin to treat various conditions including congestive heart failure.
      Potassium canrenoate is a similar drug that is also metabolized to canrenone. Due
      to reported interference of spironolactone, potassium canrenoate, and their
      common metabolite canrenone with digoxin immunoassays, we investigated potential
      interference of these compounds with Dimension Vista Digoxin immunoassay using
      Flex reagent cartridge. Aliquots of a drug-free serum pool were supplemented with
      various amounts of spironolactone, potassium canrenoate, or canrenone and
      apparent digoxin values were measured using Dimension Vista digoxin assay, we
      observed none-detected value except when aliquots were supplemented with higher
      amounts of spironolactone or canrenone. Similarly, when aliquots of a serum
      digoxin pool (prepared by pooling specimens from patients receiving digoxin)
      where further supplemented with various amounts of spironolactone, potassium
      canrenoate, or canrenone, we observed moderately falsely elevated digoxin values
      only in specimens containing higher amounts of spironolactone or canrenone. We
      conclude that spironolactone and canrenone but not potassium canrenoate may cause
      modest interference with Dimension Vista digoxin assay but such interferences may
      not be clinically significant except with very high amounts of canrenone.

PMID- 21089174
TI  - Evaluation of BD Vacutainer SSTTM II Plus tubes for common tumor marker tests by
      Roche Diagnostics Modular E 170 analyzer.
AB  - Serum separator tubes were introduced 35 years ago and were widely used in the
      clinical laboratory in China for routine collection of blood because of providing
      a closed system that allowed for collection, transport, processing, sampling, and
      storage of specimens. This type of tubes facilitated rapid separation of serum
      from cellular constituents of blood and also prevented hemolysis upon prolonged
      storage. However, there were some limitations associated with gel tubes (i.e.,
      gel and analyte stability). In order to circumvent these problems, BD released a
      new serum separator tube containing a new gel (BD SST(TM) II Plus). We
      investigated the performance of BD SST(TM) II Plus tubes for tumor marker tests
      using BD Serum Glass tubes as controls. Equivalence between the BD SST(TM) II
      Plus and BD Serum Glass tubes was demonstrated for all analytes at initial time.
      Also, all analytes remained stable when stored in BD SST(TM) II Plus tubes up to
      72  hr. Concentration of neuron-specific enolase tended to increase with
      preservation time up to 72  hr in BD Serum Glass tubes. We conclude that BD
      SST(TM) II Plus was suitable for collection of blood and storage of serum for
      tumor marker tests.

PMID- 21089175
TI  - Gene diagnosis of oculopharyngeal muscular dystrophy in a Chinese family by a
      GeneScan method.
AB  - This study aims to perform gene diagnosis for Chinese family patients with
      Oculopharyngeal muscular dystrophy (OPMD). Genomic DNAs were extracted from the
      pedigrees' members. Gene diagnosis was performed for these pedigrees' members by
      approaches, such as DNA sequencing and GeneScan. Sequence analysis and PABPN1
      genotyping showed that the mutated allele in affected members of this family has
      nine trinucleotide repeats of GCG (GCG)(9), whereas the normal allele contains
      six trinucleotide repeats of GCG (GCG)(6). The above results suggest that mutated
      GCG repeats in PABPN1 gene may cause OPMD in this family, and PABPN1 genotyping
      could be used as a convenient, highly effective, and reliable gene diagnostic
      test for OPMD patients.

PMID- 21089176
TI  - Is specific gravity a good estimate of urine osmolality?
AB  - CONTEXT: Urine specific gravity (USG) is often used by clinicians to estimate
      urine osmolality. USG is measured either by refractometry or by reagent strip.
      OBJECTIVE: We studied the correlation of USG obtained by either method with a
      concurrently obtained osmolality. DESIGN: Using our laboratory's records, we
      retrospectively gathered data on 504 urine specimens on patients on whom a
      simultaneously drawn USG and an osmolality were available. Out of these, 253
      USG's were measured by automated refractometry and 251 USG's were measured by
      reagent strip. Urinalysis data on these subjects were used to determine the
      correlation between USG and osmolality, adjusting for other variables that may
      impact the relationship. The other variables considered were pH, protein,
      glucose, ketones, nitrates, bilirubin, urobilinogen, hemoglobin, and leukocyte
      esterase. The relationships were analyzed by linear regression. RESULTS: This
      study demonstrated that USG obtained by both reagent strip and refractometry had
      a correlation of approximately 0.75 with urine osmolality. The variables
      affecting the correlation included pH, ketones, bilirubin, urobilinogen, glucose,
      and protein for the reagent strip and ketones, bilirubin, and hemoglobin for the
      refractometry method. At a pH of 7 and with an USG of 1.010 predicted osmolality
      is approximately 300  mosm/kg/H(2)O for either method. For an increase in SG of
      0.010, predicted osmolality increases by 182  mosm/kg/H(2) O for the reagent
      strip and 203  mosm/kg/H(2)O for refractometry. Pathological urines had
      significantly poorer correlation between USG and osmolality than "clean" urines.
      CONCLUSION: In pathological urines, direct measurement of urine osmolality should
      be used.

PMID- 21089177
TI  - Correction for effect of cold storage on immature platelet fraction.
AB  - It is common practice to store samples and measure the immature platelet fraction
      (IPF) only when the initial standard complete blood count and the blood smear
      indicate thrombocytopenia. However, the cold storage introduces an inherent error
      in the %IPF. A falsely elevated %IPF carries the risk of potentially misleading
      the clinicians' interpretation of the thrombopoietic activity, thus hindering the
      clinical utility of this parameter. To address this issue, we determined the IPF%
      in individual blood samples from 29 adults at 0, 4, 8, 10, 12, 21, and 24  hr
      after the blood draw. This study demonstrated that the effect of 4 degrees C
      storage is linear over a 24  hr period and independent of the initial IPF%. These
      observations have enabled the development of a proposed algorithm for a corrected
      IPF%, which is equal to the uncorrected IPF% minus 1.34 times the length of time
      in hours of storage at 4 degrees C. The proposed correction algorithm extends the
      utility of this clinically important laboratory parameter. However, care should
      be taken not to extrapolate the algorithm significantly beyond 24  hr storage,
      because the experimental data only covered this range.

PMID- 21089179
TI  - Cancer surveillance strategies in ulcerative colitis: the need for modernization.
AB  - The risk of colorectal cancer is increased in patients with long-standing
      ulcerative colitis. Traditional surveillance has centered around regular standard
      white-light colonoscopy, with multiple biopsies aimed at detecting dysplasia or
      the identification of early cancer. This has resulted in only a modest reduction
      in cancer incidence and mortality. A better understanding of disease risk factors
      may allow endoscopic resources to be more focused on patients at higher risk. In
      addition, advanced endoscopic techniques have the potential to improve dysplasia
      detection, minimize the need for routine biopsies, and allow for the removal of
      dysplastic lesions, avoiding the need for surgery. Techniques such as
      magnification colonoscopy, chromoendoscopy, narrow band imaging,
      autofluorescence, and confocal endomicroscopy may all have a role to play in
      improving the benefits of endoscopic surveillance. Revised endoscopic
      surveillance strategies are proposed, incorporating aspects of risk
      stratification, a well-established practice in noncolitis-related colorectal
      cancer screening, and some of these new technologies.

PMID- 21089180
TI  - Chrysophanic acid blocks proliferation of colon cancer cells by inhibiting
      EGFR/mTOR pathway.
AB  - Inactivation of epidermal growth factor receptor (EGFR) is a prime method used in
      colon cancer therapy. Here it is shown that chrysophanic acid, a natural
      anthraquinone, has anticancer activity in EGFR-overexpressing SNU-C5 human colon
      cancer cells. Chrysophanic acid preferentially blocked proliferation in SNU-C5
      cells but not in other cell lines (HT7, HT29, KM12C, SW480, HCT116 and SNU-C4)
      with low levels of EGFR expression. Chrysophanic acid treatment in SNU-C5 cells
      inhibited EGF-induced phosphorylation of EGFR and suppressed activation of
      downstream signaling molecules, such as AKT, extracellular signal-regulated
      kinase (ERK) and the mammalian target of rapamycin (mTOR)/ribosomal protein S6
      kinase (p70S6K). Chrysophanic acid (80 and 120 um) significantly blocked cell
      proliferation when combined with the mTOR inhibitor, rapamycin. These findings
      offer the first evidence of anticancer activity for chrysophanic acid via
      EGFR/mTOR mediated signaling transduction pathway.

PMID- 21089181
TI  - Modulation of the gamma-aminobutyric acid (GABA) system by Passiflora incarnata
      L.
AB  - Passiflora incarnata L. (Passifloraceae) is important in herbal medicine for
      treating anxiety or nervousness, Generalized Anxiety Disorder (GAD), symptoms of
      opiate withdrawal, insomnia, neuralgia, convulsion, spasmodic asthma, ADHD,
      palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction and
      menopause. However, the mechanism of action is still under discussion. Despite
      gaps in our understanding of neurophysiological processes, it is increasingly
      being recognized that dysfunction of the GABA system is implicated in many
      neuropsychiatric conditions, including anxiety and depressive disorders.
      Therefore, the in vitro effects of a dry extract of Passiflora incarnata (sole
      active ingredient in Pascoflair(r) 425 mg) on the GABA system were investigated.
      The extract inhibited [(3) H]-GABA uptake into rat cortical synaptosomes but had
      no effect on GABA release and GABA transaminase activity. Passiflora incarnata
      inhibited concentration dependently the binding of [(3) H]- SR95531 to GABA(A) 
      receptors and of [(3) H]-CGP 54626 to GABA(B) -receptors. Using the [(35) S]
      GTPgammaS binding assay Passiflora could be classified as an antagonist of the
      GABA(B) receptor. In contrast, the ethanol- and the benzodiazepine-site of the
      GABA(A) -receptor were not affected by this extract. In conclusion, the first
      evidence was shown that numerous pharmacological effects of Passiflora incarnata
      are mediated via modulation of the GABA system including affinity to GABA(A) and
      GABA(B) receptors, and effects on GABA uptake.

PMID- 21089182
TI  - Baekjeolyusin-tang and its active component berberine block the release of
      collagen and proteoglycan from IL-1beta-stimulated rabbit cartilage and down
      regulate matrix metalloproteinases in rabbit chondrocytes.
AB  - Osteoarthritis (OA) is a major degenerative disease affecting millions of
      individuals. The ability of articular cartilage to self-repair is limited due to
      a low tissue turnover rate and the avascular nature of the cartilage, making OA
      an irreversible disease. In Korea, however, many traditional Korean medical
      doctors have treated joint disease with a prescription of traditional Korean
      medicine, BaekJeolYuSin-tang (BYT). Thus, the chondroprotective effects of BYT
      and its active component, berberine (Ber) were investigated in an experimental
      model. Here it is shown that BYT or Ber significantly inhibited the expression of
      matrix metalloproteinase (MMP)-3 and a disintegrin and metalloproteinase with
      thrombospondin motifs-5 as well as increasing the expression of tissue inhibitors
      of metalloproteinase-1, aggrecan and collagen in rabbit articular chondrocytes (p
      < 0.05). BYT or Ber significantly inhibited the secretion and activity of MMP-3
      (p < 0.05). In addition, BYT or Ber significantly inhibited the release of
      collagen and glycosaminoglycan into the culture media from rabbit articular
      cartilage explants (p < 0.05). The data suggest that BYT or Ber has a therapeutic
      potential for the treatment of cartilage damage in osteoarthritis.

PMID- 21089186
TI  - How I developed the world's first evidence-based endoscopic management of carpal
      tunnel syndrome.
AB  - Carpal tunnel syndrome has been surgically treated by release of the transverse
      carpal ligament (flexor retinaculum of the hand) using a blind procedure since
      1930 or by an open procedure since 1946. The blind procedure has the possibility
      of unreliable results and ensuing complications, hence, the open procedure was
      developed. The open procedure, however, also resulted in various complications as
      reported in the 1970s. At the end of the 1970s, I had many questions regarding
      accepted surgical procedures for treatment of carpal tunnel syndrome. These
      included: "Why should any healthy tissue be injured?"; "How can I make operations
      as minimally invasive as possible?"; and "How can I shorten postoperative
      fixation periods that cause declines in activities of daily living?" This paper
      describes how I developed the world's first evidence-based endoscopic management
      procedure for carpal tunnel syndrome using local anaesthesia without a pneumatic
      tourniquet on an outpatient basis.

PMID- 21089187
TI  - Anatomical study of arcade of Struthers.
AB  - The incidence and the anatomical location of the arcade of Struthers as related
      to the arm length were studied in 62 arms of adult fresh-frozen cadavers. The
      distance between the greater tuberosity and the lateral epicondyle was designated
      as the arm length. The arcades of Struthers were identified in 85.4%. The mean
      arm length was 27.85 +/- 1.3 cm. The mean of the distance between proximal border
      of the arcade of Struthers and the medial humeral epicondyle was 8.24 +/- 2.06
      cm. The mean ratio between the distance from the proximal border of the arcade to
      the tip of the medial epicondyle and arm length was 0.29 +/- 0.07. We concluded
      that the anatomical location of the arcade as related to the arm length was 29%
      proximally, from the tip of the medial epicondyle. This report of the anatomical
      location of the arcade of Struthers related to the arm length can be useful to
      identify this structure in the arms which have differences in arm length during
      the surgical exploration and anterior transposition of the ulnar nerve
      procedures.

PMID- 21089188
TI  - Distal radial and ulnar landmarks used in percutaneous pin fixation: anatomical
      relationship to the superficial radial and ulnar nerves.
AB  - BACKGROUND: The radial and ulnar styloids as well as Lister's tubercle are
      important surgical landmarks in the surgical treatment of distal forearm
      fractures. There have been limited studies assessing their relative safety in
      terms of their distance from superficial nerves which are in danger during
      surgical procedures. The aim of this cadaveric study was to assess and compare
      the distance of superficial nerves to these important surgical landmarks.
      METHODS: Twenty embalmed cadaveric upper limbs were dissected exposing the nerves
      and tendons around the wrist. The radial styloid, Lister's tubercle, ulnar
      styloid and nerve branches were marked with pins. The distance of the nearest
      nerve branch to each landmark was measured with a digital calliper. Statistical
      analysis of the data was performed using SPSS for Windows 11.5 (SPSS Inc.,
      Chicago, IL) using Friedman Tests and Wilcoxon Signed Ranks tests. RESULTS: The
      median distance of the nearest nerve branch to the radial styloid was 5.42 mm, to
      the Lister's tubercle was 16.68 mm and to the ulnar styloid was 13.56 mm. There
      was unequal safety for these three surgical landmarks regarding proximity to
      nerve branches (p < 0.00001). Paired comparison using Wilcoxon Signed Ranks Test
      showed that the Lister's tubercle was safer than the radial styloid (p < 0.0001)
      and ulnar styloid (p = 0.04). In addition, the ulnar styloid was safer than the
      radial styloid (p < 0.001). CONCLUSIONS: There is a higher risk of injury to
      superficial nerves when operating near the radial styloid as it is significantly
      closer to nerve branches as compared to Lister's tubercle and ulnar styloid.

PMID- 21089189
TI  - The dorsal cutaneous branch of the ulnar nerve: an anatomical study.
AB  - There are significant variations in the anatomy of the dorsal cutaneous branch of
      the ulnar nerve. The dorsal cutaneous branch is at a risk of injury during a
      therapy for the ulnar side of the wrist. The purpose of this study is to measure
      the variations of the dorsal cutaneous branch. We studied 30 embalmed cadaver
      specimens. In its course, two division patterns of the dorsal cutaneous branch
      were identified, namely proximal and distal types. The proximal type went around
      the ulna proximal to the ulnar styloid process, and directed toward the
      ulnodorsal aspect. The distal type went around to the ulnodorsal aspect, distal
      to the styloid process. The proximal type was found in 21 of 30 cadavers, and the
      distal type was found in nine of 30 cadavers.

PMID- 21089190
TI  - Self-reported outcome following anterior transposition of ulnar nerve in the
      elderly.
AB  - Cubital tunnel syndrome is a common entrapment neuropathy of the upper limb. This
      condition can result in significant sensory disturbances and motor deficits in
      the distribution of the ulnar nerve. Surgical management of cubital tunnel
      syndrome is indicated when non-operative measures fail. However, in the elderly
      population, there may be a tendency to avoid surgery as nerve healing has been
      found to be poor. In our study, we reviewed the results of anterior transposition
      of ulnar nerve in patients 60 years of age and older. Our results were based on a
      self-reported outcome at a minimum of one year after surgery - 94.7% of our
      surgeries resulted in some improvement in symptoms experienced by the patients
      while there was an overall satisfaction rate of 83.3%. Based on our results, we
      recommend ulnar nerve transposition in the management of cubital tunnel syndrome
      in this group of patients if non-operative measures fail.

PMID- 21089191
TI  - "Mood rings": a new method of objective clinical assessment of peripheral nerve
      injuries.
AB  - The clinical assessment of patients with peripheral nerve injury is primarily
      dependent on subjective clinical examination. We aimed to assess whether a
      thermotropic liquid crystal ring (TLC-ring) could provide the basis for an
      objective assessment of peripheral nerve injury by detecting temperature changes
      in the digits innervated by the damaged nerve. A group of patients with known
      median, ulnar or both digital nerve injuries were compared against a control
      group. TLC-rings, marketed to the general public as "mood rings", were applied to
      the affected and unaffected digits and the colour change recorded. Areas with
      nerve damage showed a statistically significant difference in colour response to
      those without damage. This study establishes the ability of TLCs to detect
      cutaneous temperature changes associated with peripheral nerve injuries. Further
      studies and improvements are needed to refine TLC as an acute assessment tool for
      peripheral nerve injuries.

PMID- 21089192
TI  - High resolution ultrasonography of the hand and wrist: three-year experience at a
      District General Hospital Trust.
AB  - A retrospective analysis of 227 patients undergoing ultrasonography (US) of the
      hand/wrist over a three-year period in a district general hospital trust was
      performed. The usefulness in each case was assessed by two independent reviewers
      using a qualitative rating system, as (A) Useful: determines management, (B)
      Useful: contributory, (C) Not useful: not misleading, or (D) Not useful:
      misleading/potentially harmful. US was useful in 74.8% of cases but
      misleading/potentially harmful in 13.1%. Misleading rates exceeding 10% in sub
      categories including tendinopathy, carpal tunnel syndrome, foreign body and
      lumps, where US findings may influence the decision to operate or not, are
      particularly worrying. There were a number of cases where US led to unnecessary
      operations or suggested operating on the wrong structures, and also cases where
      US findings wrongly suggested that surgery was unnecessary. Various
      recommendations aimed to improve the usefulness of US in the Hand and Wrist,
      including mandatory/formal musculoskeletal US training, are made.

PMID- 21089193
TI  - Dorsally displaced fractures of the distal radius - a study of preferred
      treatment options among UK trauma and orthopaedic surgeons.
AB  - Distal radius fractures are common, and surgeons have in their armament a variety
      of ways of treating them. In this study, 50 orthopaedic surgeons in the UK were
      shown five clinical scenarios and radiographs from patients with various fracture
      patterns of the distal radius, and were asked for their preferred management.
      There was a wide variation in the preferred treatment for each scenario
      presented. Across all of the cases, 52% of surgeons preferred to use a volar
      locking-plate compared with 21% who chose fixation with Kirschner wires. There
      was very little consensus among surgeons with regard to the optimal method of
      fixation for patients sustaining dorsally displaced fractures of the distal
      radius. This disagreement is not surprising as there is currently no high level
      evidence to guide surgeons as to the best management option for this common and
      potentially debilitating injury.

PMID- 21089195
TI  - A working classification for the management of scapho-trapezium-trapezoidosteo
      arthritis.
AB  - Osteo-arthritis (OA) of the scapho-trapezium-trapezoid joint (STT) is the second
      most common involved joint after trapezium-metacarpal I OA in the wrist. The
      possible aetiology causing or contributing to the development of STT OA is
      shortly discussed. A working classification is then proposed, which assists in
      the management of STT OA.

PMID- 21089194
TI  - SLAC wrist in the absence of recognised trauma and CPPD.
AB  - PURPOSE: This comparative cohort study was designed to determine whether non
      traumatic SLAC wrist exists, and is associated with abnormal carpal bone
      kinematics (specifically, decreased lunate flexion). METHODS: SLAC patients with
      no recognised history of upper extremity trauma were prospectively compared with
      an age-matched control group. RESULTS: Thirty-five subjects (69 wrists), included
      33 non-traumatic SLAC wrists and 36 control wrists. The non-traumatic SLAC group
      had significantly different radiographic kinematic analysis compared to the
      control group. Flexion of the asymptomatic non-degenerative wrist of the non
      traumatic SLAC group was distributed 70% through the lunocapitate (LC) joint and
      only 30% through the RL joint (p < 0.05). Conversely, flexion was more evenly
      distributed in the control group (48% LC and 52% RL). The non-traumatic SLAC
      group had abnormal wrist kinematics even in the non-involved side. CONCLUSIONS:
      This study suggests that non-traumatic SLAC does exist. We believe that non
      traumatic SLAC begins with abnormal wrist kinematics and that the dorsal
      radiolunate ligament restricts lunate flexion but not scaphoid flexion, leading
      to increased SL angles and, with years, eventual attrition of the SL ligament.

PMID- 21089196
TI  - Mycobacterium marinum infection of the deep structures of the hand and wrist: 25
      years of experience.
AB  - Mycobacterium marinum infection could have various presentations, from
      superficial skin infection to deep structure destruction. The prognosis is
      relatively poor when deep structure is involved as it is more destructive. The
      prognosis is even worse when operation is required. In the retrospective study of
      136 patients who suffered this disease with deep structure involvement, their
      clinical presentations could be classified into benign and aggressive type. It
      was found that both types of presentation could be treated conservatively by
      medication alone. Benign presentations could be treated successfully with
      chemotherapy alone without complications. Patients with aggressive presentation
      were usually associated with worse prognosis as there were more complications
      regardless of the management option. Therefore, the clinical presentation not
      only had prognostic value but could also guide the treatment plan.

PMID- 21089197
TI  - Acute plastic bowing of the radius with a distal radioulnar joint injury: a case
      report.
AB  - Acute plastic bowing is an incomplete fracture with a deformation that shows no
      obvious macroscopic fracture line or cortical discontinuity. Although cases of
      acute plastic bowing of the ulna with a dislocation of the radial head have been
      previously reported, we present here a rare case of acute plastic bowing of the
      radius with a distal radioulnar joint injury in a 16-year-old boy. Internal
      fixation of the detached fragment to the ulnar styloid and repair of the
      triangular fibrocartilagenous complex resulted in the disappearance of wrist
      pain. In cases of distal radioulnar joint injuries in children or adolescents,
      radiographs of the entire forearm should be taken to evaluate the existence of
      radial bowing.

PMID- 21089198
TI  - Partial anterior interosseous nerve palsy: isolated neuropraxia of the branch to
      flexor pollicis longus.
AB  - Anterior interosseous nerve palsy is rare. Isolated neuropraxia of its branch to
      the flexor pollicis longus is even rarer. We present a case of a 24-year-old man
      who presented with weakness of his left thumb flexion after sustaining closed
      fracture of the proximal third of his left radius. On exploration, the anterior
      interosseous nerve and its branches was found to be intact as was the flexor
      pollicis longus. Electrophysiological studies demonstrated acute left anterior
      interosseous nerve neuropathy. Electromyography showed discrete motor unit at the
      flexor pollicis longus. Two months later the patient had full recovery of the
      flexor pollicis longus. We would like to highlight this rare occurrence and
      present a detailed history of this case to increase awareness amongst clinicians
      regarding this condition.

PMID- 21089199
TI  - Carpal tunnel syndrome associated with a fracture of a silicone implant for
      Kienbock's disease: two case reports.
AB  - In this report, two cases presenting with CTS including a fracture of the
      silicone implant for Kienbock's disease after replacement over 20 years
      postoperatively where CTR ceased the symptoms of CTS. The major symptom
      characteristic was the median nerve impairment with less emphasis on the limited
      range of motion of the wrist or wrist pain due to a fracture of the silicone
      implant. There was an unlikely association between the fracture of the implant
      and CTS, which was confirmed by the operative findings of tenosynovitis and
      thickness of the degenerated transverse ligament without a significant protrusion
      of the silicone implant.

PMID- 21089200
TI  - Scaphoid dislocation associated with axial carpal dissociation during volar
      flexion of the wrist: a case report.
AB  - We present the first report of a patient with an isolated scaphoid dislocation
      with axial carpal dissociation sustained during volar flexion of the wrist. The
      scaphoid was dislocated to the radial side of the radial styloid process and was
      slightly shifted to the dorsal side. It was shown that the position of the wrist
      played an irrelevant role for occurring scaphoid dislocation.

PMID- 21089201
TI  - Simultaneous fracture of the waist of the scaphoid and the hook of the hamate.
AB  - A case of simultaneous fracture of the waist of the scaphoid and the hook of the
      hamate is presented. The scaphoid fracture was treated surgically with a headless
      compression screw, while the hook fracture was treated conservatively with cast
      immobilisation for eight weeks. Both fractures achieved bone union and the
      patient returned to work without any symptoms or complications. Only two cases of
      fractures of the scaphoid and hamate have been reported previously. However, both
      of them involved fracture of the body of the hamate. This is the first report of
      simultaneous fracture of the scaphoid and the hook of the hamate.

PMID- 21089202
TI  - Accessory extensor digiti minimi muscle simulating a soft tissue mass during
      surgery: a case report.
AB  - During a wrist ganglion excision originating at the tendon sheath of the extensor
      carpi ulnaris muscle, a soft tissue mass was observed just radial and distal to
      the surgical field. Dissection of the mass revealed an accessory extensor digiti
      minimi muscle belly which joined the radial extensor digiti minimi tendon. The
      surgical impact is discussed.

PMID- 21089203
TI  - Objective assessment of the alterations in wrist mobility with the fastrak((r))
      system following dorsal capsulodesis.
AB  - The treatment for scapholunate dissociation is challenging and its management is
      varied depending on type, severity and duration of injury, and surgeon's
      preferred technique. This study aimed to objectively assess the variations in the
      range and patterns of wrist movements using the Fastrak((r)) system in patients
      having undergone Blatt's dorsal capsulodesis (BDC). The wrist movements were
      successively measured between the operated and unoperated wrists, while the
      patients performed set tasks. Seventeen patients agreed to participate in the
      study. Following BDC the mean flexion loss was 23 degrees  (range 10 degrees -38
      degrees ). However, functional tasks revealed that the BDC did not adversely
      affect the function of the operated wrist. This novel study demonstrates
      objectively the functional restrictions that patients are likely to experience
      postoperatively following BDC. It would be interesting to note the pattern of
      wrist motion using the Fastrak((r)) system in various other clinical settings.

PMID- 21089204
TI  - [The use of drinking sulfate mineral water in combination with laser and magnetic
      laser irradiation for primary prophylaxis of post-radiation
      disorders(experimental study)].
AB  - Experiments on laboratory rats have demonstrated that prophylactic use of
      drinkable sulfate mineral water in combination with laser and magnetolaser
      irradiation of adrenal glands produces a radioprotecive effect that was
      especially well apparent in the liver and less so in the testes. Simultaneously,
      the functional activity of the thymus decreased. Protection of the liver by the
      combination of the above factors was more pronounced than the effect of each of
      them applied separately.

PMID- 21089205
TI  - [Restoration of voluntary movements in adolescents with the hyperkinetic form of
      children cerebral paralysis by means of special physical exercises].
AB  - Results of a study involving 12 adolescents presenting with the hyperkinetic form
      of childrens' cerebral paralysis are reported. The principal manifestation of the
      disease in these patients was the inability to perform coordinated movements
      because of muscular dystonia and hyperkinesia. The long-term course of special
      physical exercises and two courses of training with a Heyvus training apparatus
      resulted in the improvement of statodynamic functions compared with control
      patients.

PMID- 21089206
TI  - [Kinesitherapy in the early postoperative period following intramedullary
      osteosynthesis of tibial fractures].
AB  - A program of postoperative kinesitherapy oriented to normalize the muscular force
      of the shin, reduce the time needed to restore the weight-bearing function of the
      affected leg, and treat pain syndrome has been developed for the patients
      presenting with fractures, nonunions, and pseudoarthrosis of the tibia that were
      treated using intramedullary osteosynthesis. The efficacy of the program was
      evaluated in terms of restoration of the muscular force in the shin and
      improvement of microcirculation in the affected region.

PMID- 21089207
TI  - [Topical problems of the diagnosis and rehabilitative treatment of lymphedema of
      the lower extremities].
AB  - The present review of the literature data highlights modern approaches to and
      major trends in diagnostics and conservative treatment of lymphedema of the lower
      extremities based on the generalized world experience. Patients with lymphedema
      of the lower extremities comprise a "difficult to manage" group because the
      disease is characterized by steady progression and marked refractoriness to
      various conservative therapeutic modalities creating problems for both the
      patient and the attending physician. Modern methods for the diagnosis of
      lymphedema are discussed with special reference to noninvasive and minimally
      invasive techniques (such as lymphoscintiography, computed tomography, MRT, laser
      Doppler flowmetry, etc.). During the last 20 years, combined conservative therapy
      has been considered as the method of choice for the management of different
      stages and forms of lymphedema of the lower extremities in foreign clinics. The
      basis of conservative therapy is constituted by manual lymph drainage (MLD),
      compression bandages using short-stretch materials, physical exercises, and skin
      care (using the method of M. Foldi). Also reviewed are the main
      physiobalneotherapeutic methods traditionally widely applied for the treatment of
      lymphedema of the lower extremities in this country. Original methods for the
      same purpose developed by the authors are described including modifications of
      cryotherapy, pulsed matrix laserotherapy, hydro- and balneotherapy. Mechanisms of
      their therapeutic action on the main pathogenetic factors responsible for the
      development of lymphedema (with special reference to lymph transport and
      formation) are discussed. The principles of combined application of
      physiotherapeutic methods for the rehabilitative treatment of patients presenting
      with lymphedema of the lower extremities are briefly substantiated. Special
      emphasis is laid on their influence on major components of the pathological
      process.

PMID- 21089208
TI  - [Carbon dioxide baths: state of the art].
AB  - Modern concepts of the mechanism of therapeutic action of carbon dioxide are
      reviewed with special reference to its effects on the patients with different
      pathologies undergoing treatment with the use of carbon dioxide baths. Further
      prospects for practical application of this method are discussed.

PMID- 21089209
TI  - [The 90th anniversary of Pyatigorsky State Research Institute of
      Balneolotherapeutics].

PMID- 21089211
TI  - [Effectiveness of medical rehabilitation in patients with chronic fatigue
      syndrome at a health resort].
AB  - The possibility to apply natural medicinal factors of a spa-and-resort facility
      along with targeted physiotherapeutic exposure (succinic acid electrophoresis,
      reflexo-segmental peloidotherapy) and polyoxidonium injections was evaluated. The
      study demonstrated high effectiveness of the proposed approach to medical
      rehabilitation of patients with chronic fatigue syndrome.

PMID- 21089210
TI  - [The use of drinking mineral waters and the fiber-enriched diet for the treatment
      of patients with type 2 diabetes mellitus].
AB  - This study included 160 patients (mean age 53.4 +/- 1.32 years) with type 2
      diabetes mellitus of whom 99 (61.8%) had adequately compensated metabolic
      disorders and the remaining ones suffered uncompensated disease. All the patients
      were allocated to 4 groups differing in terms of dietary therapy (two treatment
      and two control groups). It was shown that treatment with the high-fiber diet (46
      55 g/day) in combination with mineral water markedly accelerated normalization of
      blood glucose level and lipid metabolism, reduction of body weight and arterial
      pressure; moreover, it improved general efficiency of therapy.

PMID- 21089212
TI  - [Radon therapy as a component of spa-and-resort treatment of patients with
      functional hyperprolactinemia].
AB  - A method for the treatment of patients with functional hypoprolactinemia
      attributable to adhesive processes in the small pelvis has been developed based
      on the use of radon therapy in combination with acupuncture. Inclusion of this
      approach in combined spa-and-resort therapy increases its overall effectiveness
      by 18-20%, facilitates correction of hypoprolactinemia, elimination of
      hypoluteinism, recovery of regular menstruations and fertility. Taken together,
      these effects substantially improve the patients' quality of life.

PMID- 21089213
TI  - [Evaluation of the effectiveness of rectal suppositories containing a dense
      extract from licorice roots at the stage of spa-and-resort rehabilitation of
      patients with chronic infectious prostatitis].
AB  - The objective of the present paper was to evaluate the effectiveness of Suppeksol
      rectal suppositories applied either as a self-contained therapeutic means or in
      combination with natural spa-and-resort factors for the rehabilitative treatment
      of patients with chronic infectious prostatitis. It is shown that Suppeksol
      suppositories containing a dense extract from licorice roots have beneficial
      effect on all systems and organs affected by pathological processes associated
      with chronic prostatitis especially when applied in combination with natural spa
      and-resort factors.

PMID- 21089214
TI  - [Application of transcranial pulsed electrostimulation and an alternating
      electrostatic field to the treatment of "restless legs" syndrome in patients with
      Parkinson disease].
AB  - The objective of this work was to evaluate the possibility to use combined
      therapy including application of transcranial pulsed electrostimulation and an
      alternating electrostatic field to the treatment of "restless legs" syndrome
      (RLS) in patients with Parkinson disease. A total of 31 patients with this
      syndrome were available for observation. A single course of combined therapy
      resulted in a substantial (60.4%) alleviation of painful sensation in 20
      patients. Depression and anxiety decreased by 53.56% and 52.38% respectively.
      Accordingly, the quality of life increased (6.48%). In the 11 patients of the
      control group, these changes were much less pronounced; that is, painful
      sensation, depression, and anxiety decreased by 8.15%, 5.17%, and 10.11%
      respectively. It is concluded that combined therapy including application of
      transcranial pulsed electrostimulation and an alternating electrostatic field
      produced highly beneficial effect in patients with Parkinson disease and restless
      legs syndrome.

PMID- 21089215
TI  - Evaluation of an internet-based e-learning module to introduce nuclear medicine
      to medical students: a feasibility study.
AB  - BACKGROUND: The advent of electronic learning, the so-called e-learning, offers
      new possibilities for instruction in addition to the traditional face-to-face
      teaching in the education of medical students. AIM: To evaluate the additional
      educational value of a voluntary e-learning module in a nuclear medicine course
      for third-year medical students. METHODS: Twenty exemplary nuclear medicine
      patient cases from our department were developed for e-learning purposes and
      presented on the internet using the web-based training program 'CaseTrain'.
      Subsequently, three selected test cases were handled and evaluated by an
      unselected population of third-year medical students. RESULTS: One hundred and
      twenty-eight students studied the three patient cases and filled out the
      evaluation questionnaire completely. The most important result is that both the
      interest in and the subjective feeling of the knowledge level regarding the
      specialized field of nuclear medicine had increased significantly after working
      through the three e-learning cases. Ninety-seven percent of the evaluating
      students considered the use of computer-based learning useful. The subjective
      grading of the content of the cases and the handling of the software were graded
      with high marks by the participants, 1.9 and 2.0, respectively, on a linear scale
      with 1 being the best and 6 being the worst. CONCLUSION: The addition of e
      learning to face-to-face teaching as a form of 'blended learning' is highly
      appreciated by medical students, and will provide an effective medium for
      bringing better understanding of nuclear medicine to future colleagues.

PMID- 21089216
TI  - Proceedings of ICOPA (International Congress of Parasitology) XII. August 15-20,
      2010. Melbourne, Australia.

PMID- 21089217
TI  - Proceedings of the 9th International Symposium on Geological Aspects of Radon
      Risk Mapping. August 12-13, 2008. Oslo, Norway.

PMID- 21089219
TI  - Can we enhance training-induced plasticity by modulating inhibitory cortical
      circuits with transcranial stimulation? (Commentary on Mix et al.).

PMID- 21089220
TI  - Law, science, and innovation. Proceedings of a symposium. May 2009. Austin,
      Texas, USA.

PMID- 21089221
TI  - [Proceedings and abstracts of the 61st Congress of the French National Society of
      Internal Medicine. June 10-12, 2010].

PMID- 21089218
TI  - Knockdown of orexin type 1 receptor in rat locus coeruleus increases REM sleep
      during the dark period.
AB  - The locus coeruleus (LC) regulates sleep/wakefulness and is densely innervated by
      orexinergic neurons in the lateral hypothalamus. Here we used small interfering
      RNAs (siRNAs) to test the role of LC orexin type 1 receptor (OxR1) in sleep-wake
      control. In sleep studies, bilateral OxR1 siRNA injections led to an increase of
      time spent in rapid eye movement (REM) sleep, which was selective for the dark
      (active) period, peaked at approximately 30% of control during the second dark
      period after injection and then disappeared after 4 days. Cataplexy-like episodes
      were not observed. The percentage time spent in wakefulness and non-REM (NREM)
      sleep and the power spectral profile of NREM and REM sleep were unaffected.
      Control animals, injected with scrambled siRNA, had no sleep changes after
      injection. Quantification of the knockdown revealed that unilateral
      microinjection of siRNAs targeting OxR1 into the rat LC on two consecutive days
      induced a 45.5% reduction of OxR1 mRNA in the LC 2 days following the injections
      when compared with the contralateral side receiving injections of control
      (scrambled) siRNAs. This reduction disappeared 4 days after injection. Similarly,
      unilateral injection of OxR1 siRNA into the LC revealed a marked (33.5%)
      reduction of OxR1 staining 2 days following injections. In contrast, both the
      mRNA level and immunohistochemical staining for tyrosine hydroxylase were
      unaffected. The results indicate that a modest knockdown of OxR1 is sufficient to
      induce observable sleep changes. Moreover, orexin neurons, by acting on OxR1 in
      the LC, play a role in the diurnal gating of REM sleep.

PMID- 21089222
TI  - Festschrift in memory of Vincenzo Cuomo, medical doctor and man of letters on the
      Isle if Capri, crossroads of Europe.

PMID- 21089224
TI  - Retraction.

PMID- 21089225
TI  - Bibliography. Technology, education, training and information systems. Current
      world literature.

PMID- 21089223
TI  - ["Physicians over borders"].

PMID- 21089226
TI  - Photodynamic therapy with verteporfin for vasoproliferative tumour of the retina.

PMID- 21089227
TI  - Colchicine must be stopped before imaging with [18F]-methylcholine PET/CT.
AB  - Choline is an essential amino acid, which is needed for the synthesis of membrane
      phospholipids. The choline uptake pathway is increasingly applied for molecular
      imaging of proliferating tumors. We describe a patient in whom we encountered an
      unexpected finding when he was referred for a routine [18F]-methylcholine
      PET/computed tomography scan to restage his prostate carcinoma. There was only
      visualization of circulating [18F]-methylcholine and no active uptake in any
      relevant organ. Owing to this abnormal biological behavior the scan was deemed
      uninterpretable. On checking his comorbidity and medication, the patient was
      found to take colchicine on a daily basis for his gout. After discontinuation of
      colchicine, the biodistribution of [18F]-methylcholine normalized. We present a
      possible explanation for these findings, with an impact on molecular imaging of
      the choline pathway and possibly reaching beyond colchicine alone.

PMID- 21089228
TI  - Waldenstrom macroglobulinemia with pseudo-Gaucher cells.

PMID- 21089256
TI  - New thinking about abdominal aortic aneurysms. Current screening recommendations
      and less-invasive repair are under fire.

PMID- 21089257
TI  - The fracture epidemic.  With 78 million baby boomers reaching 65, improved
      prevention is key to reducing the number of fracture in our aging population.

PMID- 21089258
TI  - New cancer vaccine shows promise.  An experimental vaccine appears to block tumor
      growth in some cases of advanced cancer.

PMID- 21089259
TI  - Celiac disease breakthrough. Researchers identify toxic protein fragments;
      discovery paves the way for prevention, diagnosis, and treatments.

PMID- 21089260
TI  - Managing cholesterol may help protect against depression.  But the recent study
      also shows that the role of cholesterol differs in its effect on men and women.

PMID- 21089261
TI  - Can rheumatoid arthritis trigger periodontal disease?  I understand both are
      caused by an inflammatory response in the immune system.

PMID- 21089262
TI  - The simplification of CPR.  In most situations, mouth-to-mouth breaths aren't
      needed.

PMID- 21089263
TI  - Keeping cancer from coming back.  Should cancer survivors take vitamin
      supplements?  Aspirin may be a better bet.

PMID- 21089264
TI  - When eyes get dry and what you can try. If artificial tears didn't work, anti
      inflammatory cyclosporine drops may.

PMID- 21089265
TI  - Shingles: prevention is the way to go.  But obstacles include vaccine cost,
      Medicare reimbursement policies, and vaccine shortages.

PMID- 21089266
TI  - By the way, doctor.  My niece has been diagnosed with body dysmorphic disorder. 
      I've heard of it, but I'm not sure what it is exactly.

PMID- 21089267
TI  - [Are germ cells pluripetential?].

PMID- 21089268
TI  - [In vitro differentiation of germline cells].

PMID- 21089269
TI  - [Single-cell analysis for the specification of germ cell fate in mice].

PMID- 21089270
TI  - [Developmental program for pluripotential cells and primordial germ cells in
      mice].

PMID- 21089271
TI  - [Sexual development of germ cells].

PMID- 21089272
TI  - [Preimplantation sexing and dynamics of germline cells using X-linked GFP mice].

PMID- 21089273
TI  - [Germ cell in fish: basic biology and biotechnological applications].

PMID- 21089274
TI  - [Current topics in the regulatory mechanism underlying germline development in
      Drosophila embryos].

PMID- 21089275
TI  - [Spermatogenic stem cell system in the mouse testis].

PMID- 21089276
TI  - [Transcriptional regulation of spermatogonial stem cell self-renewal].

PMID- 21089277
TI  - [Culture and genetic modification of mouse male germline stem cells].

PMID- 21089278
TI  - [PiRNA in spermatogenesis].

PMID- 21089279
TI  - [Germ granule in mammals and its structural and molecular conservation].

PMID- 21089280
TI  - [Function of a unique germ-line organelle, nuage, in Drosophila melanogaster].

PMID- 21089281
TI  - [Regulation of gene expression in spermatogenesis].

PMID- 21089282
TI  - [In vitro spermatogenesis in zebrafish].

PMID- 21089283
TI  - [Mechanisms of asymmetric stem cell division in the Drosophila male germ line].

PMID- 21089284
TI  - [Establishment of genomic imprints in the mammalian germline and their
      maintenance in preimplantation embryos].

PMID- 21089285
TI  - [Genomic imprinting during oocyte growth].

PMID- 21089286
TI  - [Origin of viviparity and genomic imprinting in mammals: a view from a
      retrotransposon-derived imprinted gene PEG10].

PMID- 21089287
TI  - [Regulation of germ cell differentiation by histone methylation].

PMID- 21089288
TI  - [Epigenetic regulation during spermatogenesis].

PMID- 21089289
TI  - [Involvement of histone modification and histone variants replacement in genome
      reprogramming during oogenesis and preimplantation development].

PMID- 21089290
TI  - [Cell-type-specific DNA methylation profiles].

PMID- 21089291
TI  - [Regulatory role of DNA methylation during early mouse embryogenesis].

PMID- 21089292
TI  - [Cloning mice: from aspects of donor cells].

PMID- 21089293
TI  - [Nuclear transfer and ntES cell derivation from somatic cells].

PMID- 21089294
TI  - [Remodeling of somatic nuclear chromatin in Xenopus laevis eggs and their cell
      free extracts].

PMID- 21089295
TI  - [Gene expression and phenotypes of livestock clone].

PMID- 21089297
TI  - [Mammalian neural stem cells].

PMID- 21089296
TI  - [Live cell imaging of epigenetic dynamics during preimplantation development].

PMID- 21089298
TI  - [Regulation of neural development by the bHLH factor Hes1].

PMID- 21089299
TI  - [Roles of an extracellular matrix regulator RECK in mouse development].

PMID- 21089300
TI  - [Epigenetic regulation involved in fate specification of neural cells].

PMID- 21089301
TI  - [Molecular basis of cell fate regulation in the central nervous system].

PMID- 21089302
TI  - [Molecular machinery to specify subtypes of cerebellar and precerebellar
      neurons].

PMID- 21089303
TI  - [Brain patterning: region-specific gene expression and compartment/boundary
      formation].

PMID- 21089304
TI  - [Clustered protocadherin family].

PMID- 21089305
TI  - [Mechanism of neuronal migration and layer formation].

PMID- 21089306
TI  - [Isthmus organizer: regulation of cerebellar and tectal development].

PMID- 21089307
TI  - [Role of neuronal migration for neural circuit formation].

PMID- 21089308
TI  - [Neuronal polarity].

PMID- 21089309
TI  - [Generation and remodeling of diverse dendritic patterns].

PMID- 21089310
TI  - [Developmental mechanisms of glial cells].

PMID- 21089311
TI  - [Axon growth inhibition signals and strategies to treat injuries to the central
      nervous system].

PMID- 21089312
TI  - [Strategies for axonal regeneration after spinal cord injury].

PMID- 21089313
TI  - [Molecular mechanisms underlying the regulation of synapse function and the
      molecular architecture of the postsynaptic density].

PMID- 21089314
TI  - [Dynamic regulation of actin cytoskeleton in dendritic spine morphogenesis and
      synaptic plasticity].

PMID- 21089315
TI  - [P-PAT regulates AMPA receptor trafficking through PSD-95 palmitoylation].

PMID- 21089317
TI  - [TRPM7 ion channel in cholinergic synaptic vesicles].

PMID- 21089316
TI  - [Ultrastructural insights of postsynaptic glutamate receptor organization].

PMID- 21089318
TI  - [Molecular mechanisms of the vesicular recycling involved in Ca2+-dependent
      neurotransmission].

PMID- 21089319
TI  - [Regulatory mechanisms of neurotransmitter release].

PMID- 21089320
TI  - [Lamina specific circuit formation in the cerebral cortex].

PMID- 21089321
TI  - [Analysis for genes specifically expressed in the primate neocortex].

PMID- 21089322
TI  - [Semaphorin/plexin signal regulates lamina-restricted projection of hippocampal
      mossy fiber].

PMID- 21089323
TI  - [Visualization and manipulation of the emotional neural circuits in the zebrafish
      brain: study of mechanisms and roles for the asymmetry in the habenulo
      interpeduncular projection].

PMID- 21089324
TI  - [Mouse olfactory bulb is composed of two separate functional modules, one for
      innate and the other for learned odor responses].

PMID- 21089325
TI  - [Heparan sulfate regulates axon guidance].

PMID- 21089326
TI  - [Molecular bases for the pruning of redundant climbing fiber-Purkinje cell
      synapses during postnatal cerebellar development].

PMID- 21089327
TI  - [Molecular mechanisms for competitive synaptic wiring in cerebellar Purkinje
      cells].

PMID- 21089328
TI  - [Escape circuits built in teleost hindbrain segments].

PMID- 21089329
TI  - [Transcranial fluorescence imaging of experience-dependent plasticity in the
      mouse sensory cortices].

PMID- 21089330
TI  - [Sound source localization in small headed animals].

PMID- 21089331
TI  - [In vivo visualization of functional neural circuits].

PMID- 21089332
TI  - [Molecular mechanism of neural connectivity: target determination by a negative
      signal].

PMID- 21089333
TI  - [Structure-function relationships in the development of the nervous system: roles
      and regulation of intra-axonal localization of guidance receptors].

PMID- 21089334
TI  - [Functional analysis of molecules involved in synaptic plasticity in the
      cerebellum].

PMID- 21089335
TI  - [Cerebellar synaptic plasticity and motor learning].

PMID- 21089336
TI  - [Molecular and cellular mechanisms for synaptic plasticity in the hippocampus].

PMID- 21089337
TI  - [Conditional gene targeting on the pure genetic background].

PMID- 21089338
TI  - [Dopaminergic regulation of behavior and its development].

PMID- 21089339
TI  - [Genes, behaviors and psychiatric disorders].

PMID- 21089340
TI  - [Neural circuit mechanism underlying thermotaxis behavior in C. elegans].

PMID- 21089341
TI  - [Mechanisms of behavioral plasticity in C. elegans].

PMID- 21089342
TI  - [Regulatory mechanisms of the glycosylation machinery: overview].

PMID- 21089343
TI  - [Biosynthesis of O-mannosyl glycan in mammals].

PMID- 21089344
TI  - [Regulation of tissue specific expression of glycan chains].

PMID- 21089345
TI  - [Remodeling of GPI-anchored proteins].

PMID- 21089346
TI  - [Fine regulatory mechanism of glycosaminoglycan biosynthesis].

PMID- 21089347
TI  - [Biological significance of glycosyltransferase cleavage].

PMID- 21089348
TI  - [Molecular movement and metabolism of complex carbohydrates through ER/Golgi
      apparatus: overview].

PMID- 21089349
TI  - [Novel catabolic pathway of glycosphingolipids that includes a cytosolic
      glucocerebrosidase, klotho-related protein (KLrP)].

PMID- 21089350
TI  - [Transport mechanism of glycoproteins by ERGIC-53 and the disease caused by
      defect in a gene coding ERGIC-53].

PMID- 21089351
TI  - [Regulation of glycosylation in Golgi units].

PMID- 21089352
TI  - [Roles of glycosyltransferases in Notch receptor folding].

PMID- 21089353
TI  - [Nucleotide-sugar transporters, PAPS transporters, and the regulation of glycan
      synthesis].

PMID- 21089354
TI  - [Structure and function of molecular complex associated with carbohydrates or
      plasma membrane: overview].

PMID- 21089355
TI  - [Functional roles of carbohydrate-mediating signals in the nervous system].

PMID- 21089356
TI  - [Importance of core fucose in receptor function].

PMID- 21089357
TI  - [N-glycans-based regulation of integrin-mediated cell adhesion].

PMID- 21089359
TI  - [Receptor specificity of influenza viruses].

PMID- 21089358
TI  - [Functional roles of glycans for interaction between cytokines and receptors].

PMID- 21089361
TI  - [Roles of sulfated glycosaminoglycans in receptor binding].

PMID- 21089360
TI  - [Transcriptional regulation of selectin ligand expression in human leukocytes].

PMID- 21089362
TI  - [Structures and functions of glycan assemblies in the plasma membranes-
      microdomains and lipid rafts: overview].

PMID- 21089363
TI  - [Functions of sulfoglycolipids in membrane microdomains].

PMID- 21089364
TI  - [Molecular complex in the vicinity of cell membrane generating cancer
      phenotypes].

PMID- 21089365
TI  - [Regulation of insulin receptor function in microdomains].

PMID- 21089366
TI  - [Lipid rafts and heterotrimeric G proteins].

PMID- 21089369
TI  - [Inter- and extracellular functions of glycoconjugates: overview].

PMID- 21089368
TI  - [Function of NEU3 sialidase in membrane microdomains].

PMID- 21089367
TI  - [Mechanism of cellular internalization of various ligands by heparan sulfate
      proteoglycan].

PMID- 21089370
TI  - [Regulation of signal transduction by polysialic acid].

PMID- 21089371
TI  - [Recognition of CD1d/glycolipid antigen complex by NKT cells and mechanisms in
      immune regulation].

PMID- 21089372
TI  - [Polylactosamine on glycoproteins regulates immune response].

PMID- 21089374
TI  - [Mucin-mediated tumor progression].

PMID- 21089373
TI  - [Oligosaccharides in lymphocyte homing].

PMID- 21089375
TI  - [Aberrant glycosylation of immunoglobulin A and renal disease].

PMID- 21089376
TI  - [Glyco-chains recognition molecules: overview].

PMID- 21089377
TI  - [Mechanisms of action of the growth factor midkine].

PMID- 21089378
TI  - [Recent topics on immune regulation by C-type lectin].

PMID- 21089379
TI  - [Neu5Gc repression in germinal center B cells].

PMID- 21089380
TI  - [Regulation of B lymphocyte signaling by Siglecs].

PMID- 21089381
TI  - [Regulation of notch signaling by O-linked glycosylations].

PMID- 21089382
TI  - [Carbohydrate recognition and immune regulation by dendritic-cell lectin].

PMID- 21089384
TI  - [Structural gycobiology and glycodrug discovery: overview].

PMID- 21089383
TI  - [Mechanism for the growth inhibition of Helicobacter pylori by gastric gland
      mucus-specific O-glycan].

PMID- 21089385
TI  - [Structural basis for trafficking and quality control of glycoproteins by
      intracellular lectins].

PMID- 21089386
TI  - [Molecular basis of sugar-protein interaction].

PMID- 21089387
TI  - [Role of sulfatide on influenza A virus replication].

PMID- 21089388
TI  - [Control of the physiological function of antibody by its Fc oligosaccharide
      structure].

PMID- 21089389
TI  - [Analysis of aberrant glycosylation].

PMID- 21089390
TI  - [Bioinformatics and metabolome analysis: overview].

PMID- 21089391
TI  - [KEGG GLYCAN and glycome informatics].

PMID- 21089392
TI  - [Metabolome analysis for glycolipids].

PMID- 21089393
TI  - [Large-scale glycomics reveals dynamic nature of proteome].

PMID- 21089394
TI  - [Schizophrenia at adolescence].
AB  - The diagnosis of schizophrenia at adolescence is still difficult. The premorbid
      history and past family history can help with the differential diagnosis in this
      situation. Studies on the future of schizophrenic adolescents show that the
      disorder has particularly harmful consequences on the individuals' development
      and psychosocial adaptation. The risk of suicide is present. Comorbid disorders
      as cannabis abuse are discussed. Paradoxically, there are only few data about a
      productive therapy. The efficacy of prevention remains to be shown.

PMID- 21089395
TI  - [Medicamental treatment of schizophrenia].
AB  - Antipsychotics play a key role in biologic therapy of schizophrenia. Following
      the first-generation neuroleptics, associated with many extrapyramidal side
      effects (severe dystonias, parkinsonian syndrome, akatisia and late dyskinesia)
      altering patients' compliance to the treatment, one can now find a new generation
      of molecules considered as atypical antipsychotics because they rarely cause
      neurological complications. This propriety provides a better compliance, along
      with a clear decrease of late dyskinesia risk but the effectiveness compared to
      ordinary molecules is still questioned. However, some of them can cause an
      increased risk of metabolic syndrome. Some molecules such as benzodiazepines and
      some antidepressants can also be prescribed to cure schizophrenic patients.

PMID- 21089396
TI  - [Chronical care of schizophrenia].
AB  - Schizophrenia is a complex mental disease leading to many deficits that needs a
      broad range of therapeutic interventions. The recent data raises the importance
      of the cognitive revalidation even though other interventions are also necessary
      in the treatment. The asylums of the former century have experienced a slow and
      continuous process of patient's deinstitutionalization. The global knowledge of
      the disorder having progressed, new multidisciplinary and multidimensional models
      of managing are now proposed. The psychiatric rehabilitation is one of those
      models having as goal the global taking charge of the disease, from the managing
      of the symptoms to the return to a life with good quality. The great specificity
      of this rehabilitation work is that it's multidisciplinary and involves a strong
      collaboration between the medical and the psychosocial intervening party's around
      a common therapeutic project. This model brings up the notion of recovery witch
      is, not the cure but, the experience that a patient acquires as he accepts the
      situation and as he recovers the feeling of being able to get going again.

PMID- 21089397
TI  - [Management of schizophrenia in acute phase].
AB  - The different limits both of the natural progression of the condition and of the
      different phases of response to treatment are specified. Acute phase treatment
      modalities, hospitalisation as well as pharmacological are then claridied. And
      for the later in particular, parenteral treatment, oral treatment, as well as the
      different options in the contexts of treatment resistance.

PMID- 21089398
TI  - [Eole-Reseau LIENS: telephone based assistance and referral advice for primary
      care professionals confronted with mental health issues in their patients].
AB  - Eole-LIENS is an available telephone line for first-line professionnels facing,
      in their daily practice, patients or users in psychological trouble. This service
      proposes a dialogue with a third party allowing a support, a help to the handling
      of the situation, a finer orientation towards the institutions existing in the
      network.

PMID- 21089399
TI  - [Approach of acute bronchitis in general practice].
AB  - Acute bronchitis is a frequent infection in general practice. Its origin is
      usually viral, but frequently, antibiotics are prescribed in this situation,
      without any clinical benefit. There are several reasons for this, the most
      important is probably the difficulty of GP's to distinguish on clinical ground
      alone between "viral type, meaning spontaneously healing ", and "bacterial type,
      meaning potentially dangerous" acute respiratory infections. The emergence of
      bacteria resistant to antibiotics is defined by the W.H.O. as a major problem of
      public health. One of the most important measures is the diminution of antibiotic
      prescriptions. The approach outlined here will help this purpose. The combination
      of four clinical parameters (fever <38 degrees C, heart rate <100', respiratory
      rate <24' and a normal auscultation) will allow to avoid the prescription of
      antibiotics, this constellation in acute bronchitis being sufficiently
      characteristic of "a viral type" of infection. In case of doubt, the measurement
      of the CRP, allows to avoid antibiotics if the value is normal (or slightly
      elevated). This approach is valuable in adults with an otherwise normal health,
      outside severe chronic illness (which could weaken immunity) and for adults <65
      years of age.

PMID- 21089400
TI  - [Management of chronic cough].
AB  - Chronic cough, defined as lasting more than 8 weeks, is a frequent and difficult
      problem. Since 1981, the north American group of Irwin and coworkers has proposed
      a diagnostic algorithm with chronic cough being explained in a vast majority of
      cases by three possible diagnoses: asthma, chronic rhino-sinusitis and
      gastrooesophageal reflux. This algorithm has been amended in order to include
      eosinophilic bronchitis and has further been severely criticized because of
      frequent failure in clinical practice. In 2008, Pavord and Chung have proposed to
      put the emphasis in chronic cough on non specific cough hyperreactivity, with the
      aetiological factors suggested by the Irwin group acting at most as modulating
      agents. Severe or persistent chronic cough should be quantitatively assessed,
      using for instance a visual analogue scale or a cough specific quality of life
      questionnaire. Where treatment for chronic cough is concerned, the sole
      definitely effective interventions are smoking cessation and discontinuation of a
      converting enzyme inhibitor. Long term inhaled steroids are also effective in
      case of eosinophilic cough (defined on basis of eosinophilia in induced sputum or
      increased level of exhaled NO). In case of chronic cough unresponsive to the
      hereinabove described management, an antitussive agent should be considered. As
      codeine is relatively ineffective, research about new antitussive agents should
      be encouraged.

PMID- 21089401
TI  - [Exercise-induced asthma].
AB  - Exercise-induced asthma is characterized by a transient rise of the airways
      resistances, associated with asthmatic symptoms, 5 to 10 minutes after the end of
      a submaximal effort. The treatment is based on a pre-effort warming, cover the
      mouth with a mask (when the weather is cold), the use of beta-mimetic
      bronchodilators before exercise and, chronic treatment with antiinflammatory
      drugs. When the patient is not controlled, an evaluation of the lung function is
      required with a postbronchodilator control or an exercise challenge test. If the
      patient remains uncontrolled despite the treatment, others diagnostics should be
      excluded, such as vocal cords dysfunction or left heart failure.

PMID- 21089402
TI  - [Pulmonary tuberculosis].
AB  - Tuberculosis (TB) is a global health problem driven by poverty, HIV infection,
      etc. In Europe, the problem of multidrug resistance (i.e., resistance to at least
      rifampin and isoniazid) (MR) develops. The cases come essentially from the former
      U.S.S.R. In Belgium, the incidence of tuberculosis continues to decline to
      9.4/100,000 inhabitants in 2008. The percentage of MR germs is 2.8%. The
      distribution of cases is not uniform across the country. The incidence is much
      higher among people recently coming from high prevalence countries than among the
      Belgian native. The pulmonary forms of TB are more contagious and more common.
      The clinical signs are frequently non specific. The diagnosis is often mentioned
      up after performing a chest Xray and must always be confirmed by microbiological
      examination and culture of several sputum or other respiratory specimens. It is
      very important to identify the germ, M. tuberculosis complex and to test its
      sensitivity to anti-TB agents. Standard treatment consists of 4 drugs: isoniazid,
      rifampin, ethambutol and pyrazinamide for 2 months followed by rifampin and
      isoniazid for at least 4 additional months. In suspected cases of MR, 5 drugs are
      prescribed at the outset. Treatment and duration will be adjusted according to
      the results of susceptibility testing. The potential toxicities of second-line
      drugs should be well known by the physicians. Compliance of the patient is
      essential. Screening in the entourage is part of the therapeutic process.

PMID- 21089403
TI  - [Domiciliary oxygen therapy].
AB  - In Belgium, oxygen therapy is becoming more and more accessible. When oxygen is
      needed for short periods or for special indications as palliative care, an
      agreement between mutual insurance companies and pharmacists allows the
      practitioner the home installation of gazeous oxygen cylinder or of oxygen
      concentrator. When long term oxygen therapy (LTOT) is indicated for patients with
      respiratory insufficiency, the pneumologist must first ask the INAMI the
      authorization to install one of the following modalities: oxygen concentrator
      with or without demand oxygen delivery cylinder and liquid oxygen. The goal of
      LTOT is to increase survival and quality of life. The principal and well accepted
      indication for LTOT is severe hypoxemia. The beneficial effects of oxygen therapy
      limited at night or on exertion are controversial. In order to increase patient's
      autonomy, oxygen can be prescribed for ambulation, respecting prescription's
      rules. At each step of oxygen therapy implementing (indication, choice of the
      device and follow-up) the patient under oxygen may benefit from a joint approach
      between the general practitioner and the chest specialist.

PMID- 21089404
TI  - [Sciatalgy: which imaging in first intention?].
AB  - Lombosciatalgy is a very common pathology and accounts for one of the most
      important problems of the public health. Usually it is a symptom that decreases
      with medical treatment. MRI or CT examinations may be asked for when symptoms
      persist for more than 7 weeks after medical treatment, symptoms increase or if
      there is a manipulation or infiltration foreseen. When there is a doubt on the
      specific origin of the symptoms, in other words when the pathology is secondary
      to an inflammatory/infectious, traumatic or tumoral aetiology, X-rays are
      performed followed by a complementary examination by CT or MRI. A CT-scan will be
      performed mainly in the workup of pathology of the intervertebral disk, or in a
      posttraumatic setting. An MRI is advisable when there is a suspicion of a primary
      or secondary tumour, infection or inflammation and in stenosis of the spinal
      canal.

PMID- 21089405
TI  - [Imaging of the shoulder].
AB  - Clinical history and patient examination are mandatory to correctly order
      shoulder imaging. The choice of the imaging modality will depend on different
      factors. Is the shoulder stable or instable? Was there a traumatic history or
      simply repetitive microtraumas? Is the A-C joint electively tender? Generally,
      plain X-rays is the first step in the shoulder imaging. However different views
      will be adapted to the clinical examination. Double oblique standard view in
      neutral position and rotations with associated profile is the basis of the
      examination. In the case of a painful stable shoulder, ultrasound is usually the
      second step. MRI is only necessary in case of deficient ultrasound. If surgery is
      an option, CT-scan or MRI without any contrast media are useful because
      ultrasound cannot correctly predict the eventual fatty degeneration of the
      muscles that contra-indicates the surgical treatment. In the case of shoulder
      instabilities, there is no place for ultrasound. The best choice is always an
      intra-articular injection of contrast medium followed by CT-scan or MRI. Only
      these examinations are able to depict labrum lesions or bicipital desinsertion.
      Finally, the AC joint must be evaluated separately from the rest of the shoulder
      with special radiological and ultrasound incidences. Stress or dynamic maneuvers
      can be added either with X-rays or ultrasound.

PMID- 21089406
TI  - [Imaging of urinary tract infection in children].
AB  - Urinary tract infection is very common in children. Its diagnosis, management and
      treatment have led to abundant literature and many controversies. The main
      challenges are to identify patients at risk of infection and those at risk of
      complicated infections. Long-term complications include reflux nephropathy, renal
      hypertension and stage renal disease. Imaging has a triple role: to confirm the
      diagnosis in patients with equivocal clinical symptoms; to determine patients at
      risk of recurrence; prevention of infection by detecting already in utero
      patients with congenital malformation. During the acute phase, Ultrasound has an
      important role in detecting favouring conditions such as urinary tract
      dilatation. The use of color Doppler increases the sensibility and specificity of
      ultrasound. To date, DMSA scan is the key examination for demonstrating the
      parenchymal lesions. CT-scan and MRI are rarely used in this acute phase.
      Retrograde voiding cystography (RVC) will be used whenever vesico-ureteric reflux
      is suspected. A decision algorithm can be proposed bases on US and DMSA; RVC will
      be performed whenever one of them is positive. CT or MRI will be used to look for
      abscesses complicating the UTI. DMSA scan is the gold standard for detecting
      renal scanning, sequellae of the infection. In the future, the role of MRI will
      surely increase for the demonstration of uropathy acute and sequelae of the renal
      involvement.

PMID- 21089407
TI  - [Radiology of acute abdominal pain in adult patients].
AB  - The radiological evaluation of patients with acute abdominal pain has changed in
      the past decade. In most conditions, plain abdominal radiographs is an
      insensitive technique which have been replaced with US and CT. US is the initial
      imaging technique of choice for patients with suspected acute cholecystitis or
      acute gynecological abnormalities. It is also the primary method for evaluating
      pregnant women and pediatric patients. CT permits a rapid examination with high
      diagnostic accuracy and is now the imaging test of choice for most adult patients
      with acute abdominal pain. The increase in CT use result in a marked increase in
      radiation exposure in the population. Close cooperation with the referring
      physician remains essential to avoid CT scans who are not totally justified by
      medical need and unnecessary radiation exposure.

PMID- 21089408
TI  - [Geriatric day care hospital, an apport for the general practitioner in the
      management and follow-up of cognitive disorders].
AB  - The management of cognitive disorders requires a complex evaluation, especially
      since patients are frail, polypathological and because the complications are
      numerous. The general practitioner (GP) has an important role in detecting
      predictive signs but his task to specify the diagnosis and to organize the follow
      up is not easy. Evaluating the patient as well as his/her surroundings and taking
      into account the caregivers' difficulties is necessary. The number of patients
      with cognitive disorders is huge and could rise with the growth of life
      expectancy and the increased incidence of dementia for the elderly. The geriatric
      day care hospital activities are developing further in Belgium since 2006 thanks
      to the funding of pilot projects. These structures are benefiting from a
      multidisciplinary team lead by a geriatrician. This paper presents what the
      geriatric day care hospital brings to the GP in the diagnosis and the follow-up
      of cognitive disorders. The geriatric day care hospital realizes diagnosis and
      follow-up within a suited environment. The multidisciplinary teams are used to
      perform complex assessment of frail patients. The various patient comorbidities
      are evaluated taking into account both the environment in which the patient lives
      and his/her caregivers. The collected data allows the setup, together with the
      GP, of a care plan optimizing the support of the patient and his/her
      surroundings.

PMID- 21089409
TI  - [Evaluation of our psycho-educative program by participating caregivers].
AB  - Facing difficulties due to dementia syndromes, systemic care is necessary.
      Amongst therapies assessed specifically to caregivers, psychoeducative steps seem
      to be the strongest effective one on neuropsychiatrics symptoms. Psychoeducations
      tend to teach the caregivers to modify their interactions with patients via a
      better understanding of illnesses and patients. Our training "Pour mieux vivre
      avec la maladie d'Alzheimer", applied in groups of eight to twelve persons,
      consists in twelve sessions of two hours each. To assure the biggest possible
      availability, we recently incorporated the concomitant coverage of patients into
      artistic workshops. These sessions of art-therapy realized in parallel to our
      psychoeducative program will thus be estimated according to the same rigorous
      methodology. The critical evaluations realized by participants at the end of our
      program reflect the outcome of our main objective (to teach to modify
      interactions with the patients) while contributing to the improvement of social
      contacts and to the learning of calling to existing helps. These preliminary
      results strongly argue for the pursuit and even extension of this kind of
      caregiver's management.

PMID- 21089410
TI  - [How to avoid the inappropriate prescriptions in nursing homes?].
AB  - The inappropriate prescription is frequent in the Belgian nursing homes. Which
      are the better tools to control and improve our prescription? Is it relevant to
      start or continue medications for prevention in the context of moderate or severe
      dementia? STOPP-START seems to be a good screening tool for detecting the
      inappropriate prescriptions by the general practitioner.

PMID- 21089411
TI  - [Dementia in nursing home. Which support for the families?].
AB  - In caring for old people with dementia, we observe that family solidarity remains
      strong, which allows to delay nursing home admission. Emphasis is put on the
      disease altering the sense of security among old people and their families.
      Spontaneous attempts from caregivers in order to counterbalance often lead to a
      lack of energy available for change when entering a nursing home, as they have
      put a lot into making up for the affected sense of security of the failing
      relative. A complex story has then emerged from a real relationship between the
      caregivers and the disease, and this has to be taken into account in the helping
      process as much as the utter exhaustion of the family.

PMID- 21089412
TI  - [End of life of demented patients: ethical aspects].
AB  - Most people in contemporary western society die of the chronic diseases of old
      age. Whilst palliative care is appropriate for elderly patients with chronic, non
      malignant disease, few of these patients access such care compared with cancer
      patients. That patients dying with dementia have significant health care needs,
      comparable with cancer patients, is now well established. Yet, their families
      typically describe poor advance-care planning and an inadequate level of symptom
      control, with distress associated with pain, pressure sores, constipation,
      restlessness and shortness of breath. A comparison of people dying with advanced
      dementia or terminal cancer found that those with dementia were more likely to
      experience burdensome interventions and restraints and to have had poor advance
      care planning. Prognostic models that attempt to estimate survival of >6 months
      in demented patients have generally poor discrimination, reflecting the
      unpredictable nature of most nonmalignant disease. However, a number of generic
      and disease-specific predictor variables were identified that may help clinicians
      identify older, non-cancer patients with poor prognoses and palliative care
      needs. Simple, well-validated prognostic models that provide clinicians with
      objective measures of palliative status in demented patients are needed.
      Additionally, research that analyses the effect of comprehensive geriatric
      assessment and geriatric palliative care on psychosocial outcomes in demented
      patients and their caregivers is needed. Advances care planning and directives
      making before death allow meeting patient's preferences.

PMID- 21089413
TI  - [Antihypertensive drugs in 2010: old and new agents].
AB  - High blood pressure is a major cardiovascular risk factor and its treatment
      reduces the risk. Five classes of antihypertensive drugs are suitable for the
      treatment of hypertension either as monotherapy or in some combinations with each
      other: thiazide and thiazide-like diuretics, beta-blockers, calcium antagonists,
      angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists.
      The benefits of antihypertensive treatment are mainly due to lowering of blood
      pressure and are largely independent of the drug employed. For a given reduction
      in blood pressure, there is no evidence that "new" antihypertensive agents are
      superior to "old" agents. In the majority of patients, two or more
      antihypertensive drugs are required to achieve target blood pressure levels.
      Preferred drug combinations are diuretics with any of other antihypertensive
      drugs (with the exception of the combination with beta-blockers in patients at
      risk of diabetes mellitus), and angiotensin-converting enzyme inhibitors with
      calcium antagonists. On the other hand, the combination of an angiotensin
      converting enzyme inhibitor with an angiotensin receptor antagonist should not be
      employed because of a high incidence of serious adverse renal outcomes. Recently,
      the first orally active direct renin inhibitor, aliskiren, has been launched for
      clinical use. The results of ongoing long-term outcome studies will determine the
      place of aliskiren in the treatment of hypertension.

PMID- 21089414
TI  - [Enuresis: treatments recognized by EBM].
AB  - Nocturnal enuresis is a frequent pediatric disease which necessitates an
      appropriate diagnostic and therapeutic approach. In this article, we discuss the
      epidemiology and physiopathology of this condition. Available evidence suggests
      that children with monosymptomatic nocturnal enuresis could be treated by bladder
      advice, the enuresis alarm and/or desmopressin. Therapy resistant cases should be
      handled by specialist centers.

PMID- 21089415
TI  - [Treatment of Alzheimer's disease: the current situation?].
AB  - Current evidence tends to support the notion that Alzheimer's disease may be
      postponed by implementing interventions toward the potential etiologic factors
      (both risk and protective factors) (i.e., primary prevention) and by early
      detection (i.e., secondary prevention). Epidemiologic research has provided
      sufficient evidence that vascular risk factors in middle-aged and older adults
      play a significant role in the development and progression of dementia and AD,
      whereas extensive social network and active engagement in mental, social, and
      physical activities may postpone the onset of the dementing disorder. The
      tertiary prevention may help stabilize cognitive functions, reduce agitation,
      control neuropsychiatric symptoms. This tertiary prevention aims to avoid
      functional disability, and if possible, to improve quality of life for patients
      with AD. Cognitive training may help maintain cognitive function, slow down
      cognitive decline, and improve wellbeing for people with mild dementia. Current
      pharmacological treatment widely used for AD and dementia, including
      cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N
      methyl-D-aspartate-receptor antagonist (memantine), psychotropic medications are
      designed to target clinical symptoms of the disease such as cognitive and
      neuropsychiatric disturbances.

PMID- 21089416
TI  - [Contraception 2010. What's new?].
AB  - Innovation is not a synonym for progress. A good knowledge of the current
      contraceptives (composition, doses, side effects, price) and a good counselling
      remain the best guarantors of an effective contraception. The "two days later
      after aftermorning pill" can not take the place of the classic "tomorrow after
      pill". The oral contraception taken "non stop" and the "quick start" method are
      real progress. Male contraception do protect men against unwanted pregnancy.

PMID- 21089417
TI  - [Good practice and update in oral antidiabetic agents].
AB  - The epidemic of type 2 diabetes mellitus in our countries and the consequences of
      this disease on macro- and microvascular complications impose an early medical
      care and to consider it as a public health priority. The aim of this article is
      to dwell on oral antidiabetic drugs available for the treatment and to underscore
      the importance of lifestyle modifications, a key element, for decreasing diabetes
      related complications.

PMID- 21089418
TI  - [Management of type 2 diabetes in 2010. Insulins and injectable drugs: role of
      the general practitioner].
AB  - Type 2 diabetes mellitus is a complex metabolic disease inducing an important
      rise of the cardiometabolic risk. Medical care must therefore be targeted to
      multiple risk factor reduction and address all modifiable risk factors (high LDL
      cholesterol, low HDL, hypertension, hyperglycaemia, tobacco), as well as
      sedentarity and obesity. Glycaemic control aimed to achieve HbA1C < 7% is
      associated with a reduction in microvascular and macrovascular complications.
      Unfortunately, many patients do not reach these therapeutic targets. This
      progressive disease correlates with an inexorable destruction of the beta cells,
      therefore the therapeutic options must regularly be upgraded. The use of
      injectable drugs (GLP-1 agonists and insulins) are part of the general
      practitioner's therapeutic arsenal.

PMID- 21089419
TI  - [General practitioner and care procedure for diabetes].
AB  - A care procedure for type 2 diabetics was set up in Belgium in 2009. A three-way
      contract can be concluded between some patients, their general practitioner and
      their diabetologist to improve support, to promote communication among the care
      givers and to stimulate the patients' active participation and self-evaluation.
      The care teams are backed up by instructors, dieticians and podologists.
      Financial incentives have been set up for the patients as well as for the
      doctors. A global evaluation will take place in 2012.

PMID- 21089420
TI  - [The diabetic foot: the Cinderella of complications].
AB  - The problems of the diabetic foot in general are badly known by patients as well
      as caregivers. They represent yet a major health problem. Recall that if the
      ulcers are treated early and adequately, they will heal in 70 to 90% of cases.
      "The diabetic foot" encompasses the whole of the anomalies of the function and/or
      of the structure of the foot, linked directly or indirectly to hyperglycaemia.
      The involvement of nerves, arteries and infection can concentrate on the foot
      that is also called the "crossroads of complications". These various
      complications are reviewed in detail. The neuropathy mainly sensitive with the
      diminution or even the disappearance of the sensitivity to pain and its modes of
      detection as well as this awful and poorly known complication that is the Charcot
      foot. The arteriopathy sub-diagnosed and yet very frequent, its modes of
      detection and its treatment. The difficulties of diagnosis of infection, another
      serious danger for the foot, its classification and treatment. The care of the
      wounds whose size and depth are too often under-estimated, their classification
      of important prognostic value. The care of the diabetic foot wounds too often
      treated as "classic" wounds forgetting those topics mentioned above will be
      described focusing on their specific characteristics which are debridement and
      above all offloading. The importance of the primary and secondary prevention will
      be highlighted.

PMID- 21089421
TI  - [Prevalence of partner violence. Why the detection by the general practitioner?].
AB  - The problem of partner violence is often rarely detected at its very beginning by
      the generalist practitioner (GP). It is only after the patient's disclosure or
      clear physical symptoms that the GP is able to detect the situation. At this
      point the problem is generally already quite serious. It is thus necessary to
      bring forth elements to understand this phenomenon in terms of definition and
      chronicity. To know the prevalence, the escalation processes and the consequences
      on health of the victims as well as their children's are prerequisites for
      detecting these situations at an early stage. Moreover, deconstructing generally
      accepted ideas in this field will help the general practitioner consider the
      possibility of violence when he makes a diagnostic. This is what this article
      will propose, basing on the recent clinical practice guideline and on results of
      the new Belgian national survey.

PMID- 21089422
TI  - [Detection and management of partner violence by the general practitioner].
AB  - Not to many generalist practitioners are aware of their patients whom they have
      been following for a long time, are in fact subjected to the partner's violence;
      these patients consult their GP five times more than the rest of the population
      for different reasons. There exist a number of valid professional attitudes which
      permit the GP to detect early the victims of intimate violence. There is equally
      large consensus regarding attitudes accompanying these victims by the family
      doctor. This article proposes to present these proactive steps which could
      diminish the serious physical and psychological effects and even the death risk
      and in general be able to improve the care quality of these patients.

PMID- 21089423
TI  - [Interfamilial violence, medicolegal and ethical aspects].
AB  - Domestic or interfamilial violence--which is certainly not confined to
      disadvantaged social or cultural classes--is a process in which one partner
      carries against his spouse within the framework of private and privileged
      relationship (marriage, cohabitation, etc.), aggressive, violent and destructive
      behavior. All sectors of society are affected, whether urban or rural, and
      regardless of education or ethnic origin or religion. Such violence particularly
      affects women, but there are also violence perpetrated against men. This violence
      can take many forms, but we will only consider here the forensic clinical
      aspects, emphasizing the relevant legislation and medical ethics.

PMID- 21089424
TI  - [Family violence and generations].
AB  - Starting with a description of the place and function of violence inside
      families, the author raises than the topics of the professional's ethic and
      responsibility when working with family violence. It is not always easy for
      professionals to evaluate responsibilities particularly when they try to take
      into account as many contextual factors as possible. They could worry to become
      too Manichean and to see themselves as following only a linear causality.

PMID- 21089425
TI  - [Theoretic and applicative aspects of applying of formulary system in military
      medicine].
AB  - Development of the medicamental aid in military medicine can be realized only
      through the introduction of the formulary system. This system forms the
      informative-methodological basis of the achievement of socially necessary level
      of drug usage. On the basis of medical standards and analysis of sick rate the
      formulary of pharmaceuticals which can help to reduce the nomenclature of
      applying drugs, improve efficiency of medicamental aid is worked out. Medical
      service of Armed Forces of the Russian Federation has an experience in the
      development of formularies, but it is early to speak about the introduction of
      the formulary system into routine of military medicine. Development of the
      medicamental aid in military medicine on the basis of the formulary system will
      conduce to satisfying of medical and social requirements of servicemen, military
      retiree and members of their families.

PMID- 21089426
TI  - [The usage of the age-related structural changes of skin during the forensic
      medical examination of the dismembered corpses].
AB  - Age-related structural changes of skin of a neck, back, buttock, hip and forearm
      are investigated. The most expressed age changes characterizes parameters of
      factor reduction skin, thickness of epidermis, papillary and mesh layers of
      derma, depths of an arrangement grease and swear glands which have been used at
      creation of the equations plural regress for definition of age on each
      investigated site of an integument separately for men and women. The suggested
      method can be used at examination dismembered bodies, as for definition of age,
      and an belonging of separate parts to one corpse.

PMID- 21089427
TI  - [The results of the baseline therapy of the rheumatoid arthritis].
AB  - Retrospective comparative analysis of therapy of the rheumatoid arthritis was
      undertaken. The following variants of antiphlogistic prescription: inactive
      tactics (long-lasting administration of one medicine), tactics of protracted
      treatment (separate courses of disease-modifying antirheumatic drugs with long
      breaks between them), tactics of first aid (at the beginning "passive
      treatments", after the appearance of complications begun active therapy with
      cytostatics); tactics of pyramid (the order of the prescription of medicines
      corresponds to classical strategy of baseline therapy with short breaks during
      the treatment), tactics of active therapy (the early beginning of baseline
      therapy with consistent change of medicine); effectiveness and safety of long
      lasting administration of antiphlogistic in complex therapy of the rheumatoid
      arthritis.

PMID- 21089429
TI  - [Complex approach to the treatment of the diskal hernia of lumbosacral spine].
AB  - 21 patients with lumbosacral osteochondritis and diskal hernia were treated.
      Diagnosis was verified with the help of radiological method. The spinal motion
      segment after the hernia excision was fixed with the help of fixator with the
      shape memory for the prevention of post-operation instability. Thioctic acid
      showed the high effectiveness in complex treatment of radiculopathy.

PMID- 21089428
TI  - [Renal protection in the patients with idiopathic hypertensia: the possibilities
      of the combined blockade of the reninangiotensinaldosterone system].
AB  - Reninangiotensinaldosterone system is a key link in regulation of blood pressure
      and causes the target organ damage in hypertensive patients. For many years is
      not lost interest in the pharmacological blockade of RAAS in order to achieve
      target levels of BP and prevent damage target organs, particularly kidneys. Most
      recently recommended for clinical application of direct rennin inhibitor-
      aliskiren, a number of researcher have proven expressed nephroprotective effect.
      However, at present there is no unequivocal answer to the question whether there
      are advantages in combined RAAS blockade in hypertensive patients with use of
      aliskiren and angiotensinconverting enzyme inhibitor or angiotensin receptor
      blocker.

PMID- 21089430
TI  - [Awareness of knowledge of faces of the preinduction age on problems of sexually
      transmitted infections].
AB  - The necessity for examination of the level of youth awareness about the ways of
      transmission, safety products and prevention of sexually-transmitted infections
      is approved. It is recommended to begin the sexual education of scholars since 11
      12 years. Development of the educational programs must be based on results of
      analysis of systematic questionnaire of scholars.

PMID- 21089431
TI  - [Problem aspects of the medical examination for HIV-infection in the youth of
      conscription age].
AB  - The article is concerned with the verification of the medical examination for HIV
      infection in the youth of conscription age. Negative epidemiologic situation with
      HIV-infection and drug habituation increases the number of draftees unfitted for
      service for reasons of health. The data of analysis of structure and dynamics of
      detection of HIV positive people of conscription age during 1999-2008 was quoted:
      the main contingent was people from the territorial subject of Russian Federation
      with the highest index of HIV-infection prevalence. Introduction of obligatory
      medical examination for HIV-infection in the youth of conscription age can
      successfully prevent its spread among the military personnel. In this case
      expenses for the laboratory examination for HIV-infection of the whole draft
      contingent of Russian Federation will be lower than for alimentation, treatment
      and the following discharge of HIV positive servicemen.

PMID- 21089432
TI  - [Risks for disease in preinduction age and the program of the recreation
      activity].
AB  - The study of the fitness for military service in the Republic of Bashkortostan
      according to the medical examination results has shown that the common morbidity
      in draft-age adolescents increased in four times. More significant risk factors
      determining the growth of chronic non-infectious diseases in adolescents were
      found to be low physical activities (79.3%), alcohol consumption (75.2%), smoking
      (52.8%), lack night sleeping (23.1%). A trend of increasing in risk factor
      prevalence and its age association were noted. The development sanitation
      programme of adolescents has shown the high efficiency in the formation of a
      healthy life.

PMID- 21089433
TI  - [Diagnosis and correction of the vegetative dysfunction of the aircrew].
AB  - The article is concerned with the topical issue of aeromedicine--diagnosis and
      correction of the vegetative dysfunction of the aircrew. Causative factors
      leading to the dysfunction are discussed. Clinical and instrumental methods of
      the valuation of vegetative status and vegetative supporting of activity are
      studied. The data of researches is represented; the possibility of the correction
      of elicited variant of the vegetative dysfunctions with the help of drug and drug
      free modalities is evaluated.

PMID- 21089434
TI  - [From the history of the pharmaceutical specialist training for the Russian
      forces].
AB  - Demand of the army for the pharmaceutical specialists conduced to the
      organization of the training of the highly qualified Russian specialist. The
      first licensed specialists didn't have military education but were drafted into
      the army. As military-medical service advanced, it was found that military
      medicine service needed not just druggists, but the organizers of military
      medical supply. They should know military science, should be able in peace-time
      and in time of war to supply with all necessary the first aid actions and
      treatment of the wounded and ill. As a result of this, in the 20th century was
      founded and successfully worked the system of military pharmaceutists training
      and staff development and even with military education.

PMID- 21089435
TI  - [Centre of the state sanitary and epidemiological surveillance of Black Sea Fleet
      celebrates 75 years].
AB  - The history of the Centre of the state sanitary and epidemiological surveillance
      of Black Sea Fleet begun in the 1 April 1935 when the sanitary-epidemiological
      laboratory was founded. The article is concerned with the different stages of
      vivid development of this institute during 75 years. During this period
      organization, establishment and the name were changed many times. Since 2002 it
      got the current name and represents the scientific-methods institution which can
      solve the issues of sanitary-hygienic and antiepidemic supply of military
      personnel of the navy. Special attention is given to the high-readiness force.

PMID- 21089436
TI  - [Medical and psychologic monitoring for police officers: occurrence and secondary
      prophylaxis of psycho-somatic conditions].
AB  - The authors defined occurrence and progression dynamics of psycho-somatic
      diseases in police officers, in accordance with occupational activities features.
      The studies covered therapeutic influence of rehabilitation on anxiety depressive
      disorders and hemodynamic changes.

PMID- 21089437
TI  - [Phenomenon of occupational deformation of personality nowadays].
AB  - The authors analyzed destructive features of occupational development, presented
      main components of destructive development of specialists and professionals,
      justified synergetic concept of destructive professiogenesis.

PMID- 21089438
TI  - [Fatiguability and performance of comprehensive school teachers in accordance
      with length of service].
AB  - Polling covered 184 comprehensive school teachers and touched occupationally
      mediated fatiguability and performance recovery facilities. In connection to
      teachers' length of service, the parameters studied appeared to differ--that is
      caused by natural age-related differences and occupational self-selection
      process.

PMID- 21089439
TI  - [Endocrine and metabolic profile features in railway stock workers].
AB  - The studies covered physiologic features of adrenal cortex, pancreatic insular
      apparatus and carbohydrates metabolites in apparently healthy railway stock
      workers, in accordance with occupation, age, length of service and season. The
      authors proved dependence of endocrine and serum metabolic parameters on
      occupational activity type, age, length of service and season.

PMID- 21089440
TI  - [Occupationally mediated morbidity in aviation specialists].
AB  - General hygienic evaluation covered workplaces of aviation engineers and
      technicians and showed that work conditions of these occupations are
      characterized mainly by exposure to noise and infrasound, that are assigned to
      hazardous (3.4) and jeopardized (4) classes. Analysis of periodic medical
      examinations results helped to justify evidence based occupational and
      occupationally mediated diseases.

PMID- 21089441
TI  - [Using metabolic cytoprotector Remaxol for urgently increased stability towards
      acute decompression syndrome].
AB  - The article deals with evaluation of efficiency of metabolic cytoprotector
      Remaxol as a medication for urgently increased stability towards acute
      decompression syndrome at severe degree, studied in experiments on 45 outbred
      male rabbits. Single intravenous injection of Remaxol relieves oxidant effects of
      inadequate decompression, lowers number of lethal outcomes due to acute
      decompression syndrome, increases survival time in the animals.

PMID- 21089442
TI  - [Distribution of allelic variants of promotor sites of cytokine genes and
      endothelial growth factor gene among healthy subjects and patients with
      rheumatoid arthritis in a Russian Europeoid population].
AB  - The article reports results of the first study of cytokine gene polymorphic sites
      and analysis of distribution of their complexes among healthy subjects and
      patients with rheumatoid arthritis (RA) representative of the Russian Europeoid
      population; their possible prognostic significance is evaluated. Comprehensive
      analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G
      174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C
      2578A was performed for 513 residents of the Novosibirsk region showing no
      obvious signs of any diseases and 125 RA patients. The results suggest
      association of RA with certain alleles of pro- and anti-inflammatory cytokine
      genes. Complex indices reflecting combinations of genotypes of two, three, four,
      five, six and seven loci of the explored cytokine genes found in individual
      patient demonstrate their high specificity for RA. It is supposed that these
      findings can be used in further clinical studies for the development of algorithm
      designed to detect risk groups among clinically healthy subjects.

PMID- 21089443
TI  - [Specific features of etiopathogenesis of chronic pyelonephritis in children].
AB  - The paper is devoted to the key problems of etiology and pathogenesis of chronic
      pyelonephritis in children. Factors responsible for the development of primary
      and secondary pyelonephritis are discussed. Including urinary tract obstruction.
      The main stages of pathogenesis are considered with reference to the mechanisms
      of uropathogenic action of bacterial agents of pyelonephritis.

PMID- 21089444
TI  - [Interferons and other cytokines in patients with chronic pyelonephritis].
AB  - The article considers the modern views on changes in the cytokines system in
      patients with chronic pyelonephritis, which is one of the most common kidney
      disease. In this study we summarize data obtained by different researchers who
      assessed the role of cytokines for the diagnosis and prognosis of chronic
      pyelonephritis and for the application of antibacterial and immunomodulatory
      therapy of this pathology. We present results, that indicate changes in the
      interferon system of patients with exacerbation of chronic pyelonephritis under
      both standard antibiotic therapy and its combination with interferon inducers.

PMID- 21089445
TI  - [Prospects for the assessment of cardiac rhythm variability in patients with
      rheumatoid arthritis and systemic lupus erythematosus].
AB  - Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic
      autoimmune diseases associated with confirmed high risk of cardiovascular
      pathology. Most low-risk patients develop cardiovascular complications (CVC) with
      the involvement of traditional factors of limited diagnostic value which requires
      introduction of new efficacious methods for CVC prognostication. Reduced cardiac
      rhythm variability (CRV) along with increased levels of inflammation markers is
      an independent predictor of unfavourable outcome in patients with coronary heart
      disease, chronic cardiac insufficiency, diabetes mellitus, arterial hypertension,
      and metabolic syndrome; it may be a consequence of joint contribution of sympatic
      activation and inflammation to the development of atherothrombotic complications.
      This review is focused on the methods of CRV evaluation, possible mechanisms of
      mutual potentiation of autonomous nervous system disturbances and inflammatory
      process, factors responsible for cardiac autonomous dysfunction in RA and SLE.
      Much attention is given to the possibilities of correction of vegetative
      dysregulation of cardiac activity in patients with autoimmune diseases.

PMID- 21089446
TI  - [Correction of autoimmune mechanisms underlying the development of type I
      diabetes mellitus by methods of cell therapy].
AB  - The modern concept of development of autoimmune diabetes mellitus is considered.
      The authors discuss possibilities to correct immune disturbances and support?-
      cells regeneration by therapy with the use of donor pancreatic cells, bone marrow
      cells (hemopoietic and stromal) and umbilical cord blood cells.

PMID- 21089447
TI  - [Molecular mechanisms of cytostatic and chemosensitizing action of gestagens].
AB  - In this study cytostatic and chemosensitizing actions of gestagens are described.
      Cytostatic mechanisms can be divided into estrogen-mediated and independent ones.
      The former include down-regulation of estrogen receptors, induction of 17?
      hydroxysteroid dehydrogenase and estron sulfotransferase. The latter are MAP
      kinase inhibition, induction of cell differentiation and apoptosis.
      Chemosensitization by gestagens is due to inhibition of P-glycoprotein, GST and
      MRP. Another putative chemosensitization mechanisms involves mitochondrial
      transition pore (MTP), at least for such gestagens as buterol and
      acetomepregenol. Elucidation of common mechanisms of MTP and MDR regulation and
      the possible role of MTP in chemosensitization is a new direction of
      investigations into the action of steroid hormones.

PMID- 21089448
TI  - [Fyodor Ivanovich Komarov (on the occasion of his 90th birthday anniversary)].

PMID- 21089449
TI  - [Differential diagnosis of diffuse interstitial pulmonary diseases].
AB  - Classification, differential diagnosis and treatment of diffuse interstitial
      pulmonary diseases are considered. Data on their X-ray (computed tomographic) and
      morphological manifestations are presented along with analysis of efficiency of
      pathogenetic (anti-inflammatory and antifibrotic) therapy.

PMID- 21089450
TI  - [Current concepts of lithogenetic mechanism in the gallbladder and the role of
      biliary sludge in this process].
AB  - A review of current data on cholelithiasis is presented. The concept of staged
      development of the pathological process in the biliary system is considered
      starting from dysfunction of gallbladder and sphincter apparatus of extrahepatic
      biliary ducts via chronic acalculous cholecystitis to chronic calculous
      cholecystitis. Other issues discussed include biliary acid metabolism; varieties,
      composition and formation of calculi in the gallbladder; biliary sludge and its
      role in cholelithogenesis. Debatable questions of sludge nature and composition
      as well as certain terminological problems are considered.

PMID- 21089451
TI  - [On the possibility of using prokinetics in gastroenterology].
AB  - This review is concerned with the main classes of medicines stimulating the motor
      activity of the gastrointestinal tract widely used in clinical practice and
      studied in clinical trials (dopamine receptor blockers, 5-HT4- and 5-HT1-receptor
      antagonists, agonists of motilin receptors, antagonists of A type cholecystokinin
      and opioid receptors, etc.). The necessity of developing new generations of
      prokinetics is emphasized in order to improve efficiency and safety of therapy
      with these preparations.

PMID- 21089452
TI  - [Heart remodeling in case of isolated systolic arterial hypertension].
AB  - Examination of 32 patients with isolated systolic arterial hypertension (office
      blood pressure 171.9 = -3.3/79.7 +/- 0.2 mm Hg) and 54 ones with
      systolic/diastolic hypertension) 179.8 +/- 3.9/114.8 +/- 1.9 mm Hg) showed that
      the former are characterized by isolated hypertrophy of interventricular septum,
      the latter by symmetric hypertrophy of the septum and free left ventricular wall.
      Septal hypertrophy affects the initial phase of diastolic filling of the left
      ventricle as appears from longer time of isovolume relaxation and low peak rate
      of early transmitral blood flow; it does not influence diastolic function of the
      right ventricle. Hypertrophy of the free left ventricular wall disturbs the final
      stage of early diastolic filling of both right and left ventricles manifest as
      increased duration of their slowed early filling.

PMID- 21089454
TI  - [Factors affecting intima-media thickness in carotid arteries in diabetes
      mellitus of the young].
AB  - The aim of the work was to measure intima-media thickness IMT), study lipid and
      carbohydrate metabolism and factors contributing to the development of vascular
      complications in type 1 and 2 diabetes mellitus (DM) of the young. It included 63
      patients aged 18-40 years (40 with DM1 and 13 with DM2). Glycated hemoglobin was
      measured on a AzSYM immunoenzyme analyzer, lipid metabolism studied using a Cobas
      Integra 400 Plus analyzer, and IMT estimated based on the ultrasound technique
      (Volision--750 Exert with 10 MHz sensors). Patients with DM of the young showed
      higher IMT values than age-matched healthy subjects. IMT tended to increase after
      the age of 33 years and with duration of DM. DM did not cause a decrease of blood
      HDL levels. Smoking had negative effect on the vascular wall in DM patients.

PMID- 21089453
TI  - [Prevention of iodine deficiency diseases in pregnant and lactating women].
AB  - The objective of this work was to evaluate results of control epidemiological
      studies of iodine-deficiency condition in pregnant and breast-feeding women; the
      secondary objective was to develop standard prophylactic iodine dose schedule for
      these patients. The study included two groups of pregnant women treated either
      with a daily dose of 200 mcg potassium iodide (group 1, n=52) or with 300 mcg
      Kl/day (group 2, n=69). In all of them, blood TSH, free thyroxin and antithyroid
      peroxidase antibody levels were measured along with iodine excretion in urine.
      Thyroid volume was determined by ultrasound. Initially, median urinary iodine
      excretion in all the patients was 62.7 mcg/l. Three months after onset of the
      treatment with potassium iodide it significantly increased to 83.5 mcg/l and
      1120.8 mcg/l in groups 1 and 2 respectively (p = 0.006 and 0.001). However, the
      desired level of >150 mcg/l was not achieved. Treatment with KI in the period of
      lactation within 2 months after delivery resulted in median urinary iodine
      excretion of = >100 mcg/l in 10.5% of the women in group 1. None of the patients
      in group 2 showed the required iodine concentration in the urine. It means that
      the minimal daily prophylactic dose of iodine for pregnant and lactating women
      should be 300 mg.

PMID- 21089455
TI  - [Cardiac autonomous neuropathy and metabolic syndrome in patients with type 2
      diabetes mellitus].
AB  - Cardiac autonomous neuropathy (CAN) is a rare complication of diabetes mellitus
      (DM) that impairs the patient"s quality of life and prognosis. Despite evidence
      if common pathogenetic mechanism of metabolic syndrome (MS) and autonomous
      dysfunction, the relationship between CAN and MS in type 2 DM remains poorly
      known. We examined 157 patients with DM to study manifestations of CAN depending
      on the presence of MS components. MS was diagnosed using WHO criteria and CAN
      based on two or more pathologic results in Ewing"s cardiovascular tests (deep
      respiration test, Valsalva test, orthostatic test with estimation of HR and AP).
      The patients were allocated to 4 groups to evaluate clinical symptoms of CAN,
      cardiac rhythm variability and daily AP profile. Group 1 comprised 14 patients
      without CAN presenting with not more than one component of MS, group 2 16
      patients without CAN with 2-3 components of MS, group 3 108 patients with CAN and
      not more than one component of MS, group 4 108 patients with CAN and 2-3 with
      component of MS. Overall CAN prevalence was 80.9%. The occurrence of CAN
      positively correlated with peripheral polyneuropathy, arterial hypertension,
      severity of DM, AP, and the number of MS components. The presence of CAN and/or 2
      and more MS components associated with lowered index of cardiac rhythm
      variability (LF/HF) indicative of disturbed sympatovagal balance. The daily AP
      profile in patients with CAN and 2 or more MS components was characterized by
      anomalous nocturnal drop. Combination of CAN with 2 or more MS components was
      associated with the most unfavourable night time AP profile.

PMID- 21089456
TI  - [Socio-medical implications of education of patients with chronic obstructive
      pulmonary disease].
AB  - Effectiveness of education in patients with chronic obstructive pulmonary disease
      depends not only on enhancement of their awareness and compliance but also on
      psychoemotional status determining quality of life. This study concerns
      sociomedical implications of patients" education with reference to its influence
      on their psychoemotional condition and quality of life. It is shown that
      education not only improved health characteristics of the patients but also
      significantly reduced psychoemotional tension. These data were obtained using the
      Zung and SF-36 questionnaires. They demonstrate the importance of education and
      emphasize its role in the improvement of psychoemotional condition and quality of
      life.

PMID- 21089457
TI  - [Somatopsychic manifestations in patients with chronic viral hepatitis].
AB  - The aim of the work was to study somatopsychic manifestations in patients with
      chronic viral hepatitis (CVH). MMPI profiles, state and trait anxiety were
      assessed in 110 patients. Boundary psychic problems were evaluated using the Beck
      scale. It was shown that mean MMPI T-score in patients with CVH was above 50;
      half of them developed "neurotic triad"; hypochondria occurred in 37.3%,
      depression in 42.7%, and hysteria in 37.1%. The highest level of state anxiety
      was documented in patients with HCV infection and isolated HBCor At. The CVH-1b
      genotype was associated with enhanced occurrence of depression in patients having
      virus-positive blood for 1-5 years. The level of state and trait anxiety in them
      was lower than in patients with duration of viremia over 5 years.

PMID- 21089458
TI  - [Effect of acute and chronic alcoholic intoxication on immunological status of
      patients with generalized peritonitis in the course of therapy].
AB  - Generalized peritonitis is one of the most adequate clinical models of
      inflammatory processes with pronounced polyorgan insufficiency in which
      immunological reactivity may be substantially modified by any intoxicant of
      exogenous origin, e.g., alcohol. The aim of the present work was to assess
      immunological status of patients with generalized peritonitis associated with
      acute and chronic alcoholic intoxication treated by discrete plasmapheresis. A
      total of 152 men (mean age 49.7 +/- 1.2 years) were examined in Novosibirsk city
      clinical hospital No 2. Peritonitis developed within the average of 48.2 hours.
      All the patients with peritonitis experienced a change of immunological
      responsiveness under effect of such powerful complicating factor as alcoholic
      intoxication.

PMID- 21089459
TI  - [The use of cycloferon in the combined treatment of tuberculosis patients
      infected with HIV and viral hepatitis].
AB  - The study was designed to evaluate efficiency of 8-week treatment of 86 patients
      with tuberculosis and concomitant mild hepatitis B using cycloferon tablets. This
      therapy had beneficial effect on the symptoms of intoxication syndrome and
      respiratory manifestations of tuberculosis; in addition, it improved hemograms.
      By the end of the treatment the frequency of sputum abacillation was 4.9 times
      and positive X-ray dynamics (cavity closure) 2.2 times higher than in control.
      Therapy positively influenced hepatic function assessed from activity of
      cytolitic enzymes and bilirubin level; also, it improved serum levels of total
      protein.

PMID- 21089460
TI  - [Efficiency of polyoxidonium in combined therapy in patients with generalized
      peritonitis].
AB  - Emergency abdominal surgery for peritonitis is a topical problem awaiting
      solution. Disturbed immune status of patients with peritonitis dictates the
      necessity to supplement postoperative intensive therapy by medical preparation
      normalizing immune functions. We have studied 36 patients with generalized
      peritonitis of different etiology of whom 20 (controls) were treated by
      traditional methods and 16 received standard therapy plus polyoxidomium. The
      frequency of abdominal and other complications in the latter group decreased to
      19.2% and lethality to 13.8% while duration of the hospital stay was reduced by
      3.6 patient days.

PMID- 21089461
TI  - [Correction of tissue hypoxia with reamberin in severe forms of acute
      intoxication with neurotropic poisons].
AB  - Examination and treatment of 66 patients severely intoxicated with neurotropic
      poisons showed that inclusion of reamberin in combined therapy decreased the
      degree of tissue hypoxia as apparent from increased oxygen consumption, oxygen
      utilization index, and arteriovenous oxygen difference. This in turn accelerated
      recovery of antioxidant protection and lowered activity of lipid peroxidation.
      The use of reamberin for the treatment of acute neurotropic intoxication improves
      clinical conditions of the patients by decreasing duration of the comatose state,
      requirement for intensive therapy, and lethality.

PMID- 21089462
TI  - [Acute secondary iatrogenic thrombocytopenia in middle-aged patients].
AB  - Iatrogenic blood diseases are a primary concern for both patients and physicians.
      Pathology of blood coagulation system associated with pharmacotherapy has been
      studied in Samara regional Hemostasiological Centre during the last 30 years. A
      clinical case of secondary iatrogenic thrombopenic purpura is reported in a
      patient with a history of uncomplicated allergologic disorder. The disease
      developed after intake of several drugs at non-toxic doses.

PMID- 21089463
TI  - [Congenital polycystic renal disease with concomitant liver fibrosis].
AB  - The author presents a case of hereditary disease with polycystic kidneys and
      hepatic fibrosis complicated by portal hypertension.

PMID- 21089464
TI  - [Problems of hereditary changes in connective tissue and their possible
      solutions].

PMID- 21089465
TI  - [Real and imaginary successes in clinical diagnostics].

PMID- 21089467
TI  - [Why ethical committees in hospitals?].

PMID- 21089466
TI  - [Clinical thinking: formation and development].

PMID- 21089468
TI  - [Regulatory network of chromosome cycle].

PMID- 21089469
TI  - [Regulation of initiation of DNA replication in through G1 to S phases:
      overview].

PMID- 21089470
TI  - [Establishment of spatial and temporal program for mammalian chromosome
      replication].

PMID- 21089471
TI  - [RB/E2F regulation of DNA replication and genomic stability].

PMID- 21089472
TI  - [PreRC formation in Xenopus egg extract: beyond the identification of factors,
      toward the understanding of regulation systems].

PMID- 21089473
TI  - [Regulatory mechanisms for the initiation of chromosomal replication in E. coli].

PMID- 21089474
TI  - [Complex formation of replication proteins to initiate eukaryotic chromosome DNA
      replication].

PMID- 21089475
TI  - [Regulation of DNA replication by cell cycle and chromatin structures].

PMID- 21089476
TI  - [Regulation of MCM helicase activity].

PMID- 21089477
TI  - [Regulation and DNA damage/replication stress responses at the eukaryotic
      replication fork complex: overview].

PMID- 21089478
TI  - [Regulation of the replication fork activity by clamp and clamp loader
      complexes].

PMID- 21089479
TI  - [Replication fork stabilization by replication stress checkpoint control].

PMID- 21089480
TI  - [DNA damage tolerance through replication bypass of stalled replication forks].

PMID- 21089481
TI  - [Role of histone modification in DNA damage response].

PMID- 21089482
TI  - [Repair and translesion synthesis of UV-induced DNA lesions in mammalian cells].

PMID- 21089483
TI  - [Regulation of mitosis and chromosome segregation: overview].

PMID- 21089485
TI  - [Five outstanding questions concerning condensins].

PMID- 21089484
TI  - [Generality and diversity of bacterial chromosome segregation].

PMID- 21089486
TI  - [Blinkin: a kinetochore protein responsible for spindle checkpoint and
      microtubule-attachment].

PMID- 21089487
TI  - [Mechanisms of de novo formation of centromere/kinetochore structures].

PMID- 21089488
TI  - [Regulatory mechanism of sister chromatid cohesion at centromere].

PMID- 21089489
TI  - [Regulation of mitosis by mitotic kinases].

PMID- 21089490
TI  - [Mechanisms of recombination on chromosomes: overview].

PMID- 21089491
TI  - [Function of homologous recombination-mediated DNA repair].

PMID- 21089492
TI  - [Formation of DNA double-strand breaks in meiosis].

PMID- 21089493
TI  - [Molecular mechanism of meiotic crossover formation].

PMID- 21089494
TI  - [Mechanisms of chromosomal DNA strand break repair in human cells].

PMID- 21089495
TI  - [Regulation of homologous recombination: old and new roles of cyclin-dependent
      kinases].

PMID- 21089496
TI  - [Chromatin regulation in the chromosome cycle: overview].

PMID- 21089497
TI  - [Heterochromatin as a dynamic higher order chromatin structure].

PMID- 21089498
TI  - [Regulation of chromatin assembly during DNA replication].

PMID- 21089499
TI  - [Cell-cycle dependent histone acetylation].

PMID- 21089500
TI  - [Dynamism of chromatin-structural changes in cellular senescence].

PMID- 21089501
TI  - [Regulation of telomere DNA by telomere-specific chromatin structure].

PMID- 21089502
TI  - [Coupling and coordination of events regulating chromosome cycle: overview].

PMID- 21089503
TI  - [Regulation of various chromosome transactions by Cdc7 kinase].

PMID- 21089504
TI  - [Emerging roles for components of pre-replication complexes in chromosomal
      dynamics].

PMID- 21089505
TI  - [Collaboration of replication, recombination and noncoding transcription for gene
      amplification].

PMID- 21089506
TI  - [Passing through cohesin ring by replication forks and establishment of sister
      chromatid cohesion: what's the connection?].

PMID- 21089508
TI  - [Overview: New directions for the studies of association between chromosome
      dynamics and human diseases].

PMID- 21089507
TI  - [Homologous chromosome pairing: another climax of meiosis].

PMID- 21089509
TI  - [Cell cycle checkpoints and cancer].

PMID- 21089510
TI  - [Mitotic regulation and carcinogenesis].

PMID- 21089511
TI  - [Chromosomal instability and carcinogenesis].

PMID- 21089512
TI  - [DNA double strand break and Nijmegen breakage syndrome].

PMID- 21089513
TI  - [Fanconi anemia and DNA-damage response network].

PMID- 21089514
TI  - [Interface between viruses and host].

PMID- 21089515
TI  - [Cytoplasmic recognition of viral nucleic acids by intracellular viral sensors].

PMID- 21089516
TI  - [Propagation strategies of measles virus].

PMID- 21089517
TI  - [Filovirus infection and host factors].

PMID- 21089518
TI  - [Identification of host factors involved in influenza virus replication].

PMID- 21089519
TI  - [Host factors involved in regulation of the influenza virus replication].

PMID- 21089520
TI  - [Reverse genetics system for rotavirus and its potential for analyzing the
      pathogenesis].

PMID- 21089521
TI  - [Host factors involved in regulation of replication and pathogenesis of hepatitis
      C virus ].

PMID- 21089522
TI  - [Analysis of HIV replication and future HIV therapy].

PMID- 21089523
TI  - [Replication mechanisms and molecular pathogenesis of herpes simplex viruses].

PMID- 21089524
TI  - [Novel mechanism of herpes simplex virus type-1 infection].

PMID- 21089525
TI  - [Bacteria, infection, and immunity].

PMID- 21089526
TI  - [New insights into the bacterial secretion systems for virulence factors].

PMID- 21089527
TI  - [Strategy of Staphylococcus aureus infection to the host].

PMID- 21089528
TI  - [Mechanisms of immune evasion by Streptococcus pyogenes].

PMID- 21089529
TI  - [Shigella strategy for host defense and mucosal infection].

PMID- 21089530
TI  - [Survival strategy of intracellular bacteria in macrophages].

PMID- 21089531
TI  - [Bacterial infection and autophagy].

PMID- 21089532
TI  - [Carcinogenic mechanisms of Helicobacter pylori].

PMID- 21089533
TI  - [Immunological protection against Mycobacterium tuberculosis infection].

PMID- 21089535
TI  - [Host-pathogen interactions: parasites].

PMID- 21089534
TI  - [TLR5+ DC-mediated immune response to bacterial infection in the intestine].

PMID- 21089536
TI  - [Mechanisms of liver invasion by malaria sporozoites].

PMID- 21089537
TI  - [Immune evasion mechanisms of malaria parasites].

PMID- 21089538
TI  - [Breakthrough for the post-genome malaria vaccine candidate discovery: wheat germ
      cell-free protein production system].

PMID- 21089539
TI  - [Toxoplasma gondii as a plant: plant hormone and calcium signaling].

PMID- 21089540
TI  - [Host immune response to Trypanosoma cruzi and its evasion mechanism].

PMID- 21089541
TI  - [Role of IL-12 cytokine family in protozoa infection].

PMID- 21089542
TI  - [Gastrointestinal nematode infection and host defence: protective role of IL-18
      for nematode infection].

PMID- 21089543
TI  - [New paradigm on host defence mechanisms].

PMID- 21089544
TI  - [CD25+CD4+ regulatory T cells in infection].

PMID- 21089545
TI  - [Induction of Th17 cell differentiation in intestinal mucosa].

PMID- 21089546
TI  - [Recent progress for the development of mucosal vaccine].

PMID- 21089547
TI  - [Immunological mechanism of DNA vaccine efficacy].

PMID- 21089548
TI  - [Immune semaphorins: involvement of semaphorins in various phases of immune
      responses].

PMID- 21089549
TI  - [Novel system for CTL regulation triggered by PIR].

PMID- 21089550
TI  - [Activity change of small GTPases Rac1 and Rab5 during phagocytosis].

PMID- 21089551
TI  - [Regulation of inflammation by autophagy].

PMID- 21089552
TI  - [Mincle, as a sensor for damaged cells].

PMID- 21089553
TI  - [Infectious diseases: irrational and realistic uncertainties].

PMID- 21089554
TI  - [What is the optimal duration of antibiotics in common infections?].
AB  - Defining the optimal duration of antibiotic treatments is crucial to reduce
      toxicity and the emergence of resistance. Community acquired pneumonia can be
      treated in 5 days when the clinical response is rapidly favorable, as determined
      by simple clinical criterias. Acute cystitis can be treated by a 5-day course of
      nitrofurantoine, or 3 days of trimethoprim-sulfamethoxazole, saving the use of
      quinolones for complicated urinary tract infections or when the upper urinary
      tract is involved. Antibiotics are rarely needed for the treatment of sinusitis.
      When indicated, a 5-day course should suffice. There is no consensus for the
      duration of antibiotic treatment in skin infections. The benefit of inflammation
      biomarkers to diminish the duration of antibiotics has not yet been established
      for common infections.

PMID- 21089555
TI  - [Diseases and pathogenic agents transmitted by ticks in Switzerland].
AB  - Among the 20 tick species described in Switzerland, Ixodes ricinus, the most
      frequent one, is implicated in the transmission of pathogenic agents. Lyme
      borreliosis and tick-borne encephalitis (TBE) are the major tick-borne diseases
      transmitted to human. Presently 5 Borrelia species, belonging to the group
      Borrelia burgdorferi, are recognized as human pathogens. The risks of infection
      depend on the stage of the vector, the multiple hosts, the pathogenic agent, as
      well as human behavior in nature. The detection of other pathogenic agents in
      ticks: Anaplasma, Babesia and Rickettsia predispose to infections or co
      infections. Results of sero-epidemiologic studies suggest human infections.
      Active surveillance by physicians is necessary and clinical studies are required
      to evaluate the importance of these infections in Switzerland.

PMID- 21089556
TI  - [Clostridium difficile: a serious outpatient infection?].
AB  - Secondary to severe hospital outbreaks due to hypervirulent strains of
      Clostridium difficile, several surveillance systems in North-America and Europe
      observed an increase in infections due to this micro-organism, also in the
      outpatient setting. The case reported in the present article illustrates the
      fulminant presentation that a C. difficile colitis can show in a previously
      healthy person without prior contact with healthcare facilities. It introduces a
      review of some recent publications on the current changes in the epidemiology,
      clinical presentation, diagnosis and treatment of this disease.

PMID- 21089557
TI  - [Septic arthritis].
AB  - Septic or acute bacterial arthritis is a medical emergency. The primary physician
      must suspect this condition even when clinical symptoms are non specific or with
      simultaneous inflammatory arthropathy. Septic arthritis can have serious
      complications. Optimal care requires hospital admission in general. Synovial
      fluid aspiration and its correct interpretation, the appropriate choice and
      timely administration of empiric antibiotic therapy can limit destruction of the
      joint's cartilage. The adaptation of the antibiotic regimen after reception of
      microbiological results and the adequate treatment in full length require
      interdisciplinary collaboration between the hospital physician, including the
      specialist in infectious diseases, the microbiology laboratory and post-hospital
      care.

PMID- 21089558
TI  - [Severe CMV infection: not only in immunocompromised patients].
AB  - In presence of immunosuppression Cytomegalovirus (CMV) infection can cause severe
      and potentially fatal infection involving multiple organs. In healthy
      immunocompetent individuals CMV usually causes an asymptomatic or mild infection
      with spontaneous cure. No specific therapy is needed. Rarely, however, the
      primary infection can be severe with multiple organs injuries and fatal cases are
      described. In these situations antiviral therapy is indicated and the clinical
      and biological response is very rapidly good. We describe a clinical case and
      present a review of the literature.

PMID- 21089559
TI  - [Diagnostic of Pneumocystis jirovecii pneumonia in a non HIV patient].
AB  - Pneumocystis jirovecii pneumonia is an opportunistic infection affecting not only
      HIV patient but also patients with others causes of immunosuppression. The
      reference method for the diagnostic is the direct visualization of the pathogen
      in induced sputum or in bronchoalveolar lavage with a low sensibility. Direct
      immunofluorescence does not increase significantly this sensibility on IS. The
      PCR has been demonstrated to have 100% sensitivity. This gives rise to the
      problem of falsely positive results in patients, colonized by P. jiroveci (8,9
      26,9%) but suffering from a pneumonia due to another pathogen. Use of
      quantitative PCR or serum beta-D-glucan, might be helpful to distinguish
      colonization from infection. This paper reviews the literature on the diagnostic
      of PCP in non HIV patients.

PMID- 21089560
TI  - [Information to research subjects: where do we stop?].

PMID- 21089561
TI  - [Are all illegal drugs soon to be legal? (5)].

PMID- 21089562
TI  - [The genetic origin of hyperactivity disorder].

PMID- 21089563
TI  - [Does respect for the human body end with death? (2)].

PMID- 21089564
TI  - [Medicine: the question of goals].

PMID- 21089565
TI  - [Integration research of structural biology and chemical biology focused on drug
      discovery].

PMID- 21089566
TI  - [Development of technologies for site-specific incorporation of non-natural amino
      acids into proteins and cell-free protein synthesis system. Overview].

PMID- 21089567
TI  - [Membrane protein production using wheat germ cell-free system].

PMID- 21089568
TI  - [ PURE system: a reconstituted cell-free protein synthesis system].

PMID- 21089569
TI  - [Protein refolding].

PMID- 21089570
TI  - [Development and application of technologies for site-specific incorporation of
      non-natural amino acids into proteins].

PMID- 21089571
TI  - [Development of innovative methods to support crystallization of eukaryotic
      membrane proteins: crystallizability-based target selection using GFP fusion
      technique and folding-controlled protein expression in methylotrophic yeast].

PMID- 21089573
TI  - [Development of beam line X-ray crystallography targeting multiprotein complexes:
      Overview].

PMID- 21089572
TI  - [Development of a novel affinity tag system for the next generation structural
      biology].

PMID- 21089574
TI  - [Aims and perspectives of protein micro-crystallography].

PMID- 21089575
TI  - [Structure determination of proteins without preparing derivative crystals].

PMID- 21089576
TI  - [Development of the crystal mounting method for the protein structure
      determination without heavy-atom labels].

PMID- 21089577
TI  - [Development of automatic crystal mounting system commonly utilizable for SPring
      8 and photon factory].

PMID- 21089578
TI  - [Development of data processing technique for diffraction data collection from
      micro-crystals].

PMID- 21089579
TI  - [Solid-state NMR for structural analysis of membrane protein complexes].

PMID- 21089580
TI  - [Progress in structural studies of larger proteins by the SAIL-NMR method].

PMID- 21089581
TI  - [Establishment of chemical library and management systems for providing chemical
      samples].

PMID- 21089582
TI  - [General library: the compound selection around a variety of chemical spaces].

PMID- 21089583
TI  - [Establishment of screening basis].

PMID- 21089584
TI  - [Information platform of targeted proteins research program].

PMID- 21089585
TI  - [Structural bioinformatics].

PMID- 21089586
TI  - [Design of compound libraries for use in drug discovery].

PMID- 21089587
TI  - [Construction of natural products library and its usage for drug discovery].

PMID- 21089588
TI  - [Basic detection methods for protein-protein interaction inhibitors].

PMID- 21089589
TI  - [High throughput cell based assay].

PMID- 21089590
TI  - [Mass spectrometric approach of proteomics].

PMID- 21089591
TI  - [Identification of specific binding protein using affinity resins for discovery
      of drug target].

PMID- 21089592
TI  - [Recent advances in structure-based drug discovery].

PMID- 21089593
TI  - [Practical in silico structure-based drug design].

PMID- 21089594
TI  - [Functional structures of GPcrs for recognition of various ligand structures].

PMID- 21089595
TI  - [Structural studies on G protein-coupled receptors].

PMID- 21089596
TI  - [Fragment-based lead discovery from smaller fragments to functional ligand].

PMID- 21089597
TI  - [NMR in the fragment-based drug discovery].

PMID- 21089599
TI  - [From systematic analysis of protein interaction networks to chemical biology].

PMID- 21089598
TI  - [Practice of fragment-based lead discovery by X-rays].

PMID- 21089600
TI  - [Protein-protein interaction analysis by NMR].

PMID- 21089601
TI  - [Integrative in silico approach to assess the druggability of protein-protein
      interactions].

PMID- 21089602
TI  - [Roles of tomosyn in regulated synaptic vesicle fusion].

PMID- 21089603
TI  - [Towards structure-based design of novel inhibitors for V-ATPase].

PMID- 21089604
TI  - [Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of
      orthogonality].

PMID- 21089605
TI  - [Structural basis for dynamic formation and mechanistic actions of huge and
      complicated proteolytic machinery].

PMID- 21089606
TI  - [Development of anti-trypanosome drugs targeting nucleotides biosynthesis and red
      ox regulatory pathway].

PMID- 21089607
TI  - [Structure and function analysis of gamma-secretase complex toward development of
      therapeutics for Alzheimer's disease].

PMID- 21089608
TI  - [Structure of reactive oxygen-producing NADPH oxidase and its activation
      mechanism].

PMID- 21089611
TI  - [ESP family peptides and vomeronasal receptors in rodents].

PMID- 21089609
TI  - [Structural and functional analysis of regulatory factors involved in antibiotic
      production in Streptomyces].

PMID- 21089610
TI  - [Structural aspects of florigen to understand the molecular mechanism of
      flowering].

PMID- 21089612
TI  - [RNA program plays a central role in gene regulation].

PMID- 21089613
TI  - [Molecular mechanism of exon definition and alternative splicing].

PMID- 21089614
TI  - [Analysis of the regulatory mechanism for the constitutive splicing using
      molecular genetics in fission yeast].

PMID- 21089615
TI  - [Visualization of alternative splicing events in vivo].

PMID- 21089616
TI  - [Possible involvement of snoRNA in alternative splicing regulation].

PMID- 21089617
TI  - [Phosphorylation-dependent regulation of pre-mRNA splicing].

PMID- 21089618
TI  - [Intron turnover in eukaryotes].

PMID- 21089619
TI  - [Initiation mechanism of mRNA decay].

PMID- 21089620
TI  - [Regulation of spermatogenesis by polyadenylation and deadenylation of mRNAs].

PMID- 21089621
TI  - [Phosphorylation of the RNA polymerase II CTD coordinates transcription with mRNA
      processings].

PMID- 21089622
TI  - [RNA modification/editing and regulatory gene expression].

PMID- 21089623
TI  - [Analysis of RNA modification in zebrafish].

PMID- 21089624
TI  - [Maturation and longevity of mRNA in chloroplasts: the functions of PPR proteins
      in RNA editing and the molecular mechanisms of RNA stability control in
      chloroplasts].

PMID- 21089625
TI  - [Coordinated pathway of nuclear mRNA export reveled by the genetic analysis in
      yeast].

PMID- 21089626
TI  - [Regulation of nuclear export and cytoplasmic localization of mRNAs by NXF family
      proteins].

PMID- 21089627
TI  - [Control of RNA distribution between the nucleus and cytoplasm].

PMID- 21089628
TI  - [Dynamics of tRNAs in their life].

PMID- 21089629
TI  - [Nuclear bodies and their significance for RNA biogenesis].

PMID- 21089630
TI  - [RNA localization].

PMID- 21089631
TI  - [Planarian RNA world].

PMID- 21089632
TI  - [Germ granule formation and distribution in C. elegans].

PMID- 21089633
TI  - [RNA regulation in C. elegans germline sexual differentiation].

PMID- 21089634
TI  - [Mechanisms underlying maternal RNA translation and localization during
      Drosophila oogenesis].

PMID- 21089635
TI  - [Cytoplasmic RNP complexes in Xenopus oocytes].

PMID- 21089636
TI  - [RNA granules and local translation in neuronal dendrites].

PMID- 21089637
TI  - [The mRNA localization for cytoplasmic splicing].

PMID- 21089638
TI  - [Quality control as a master regulator of RNA program].

PMID- 21089639
TI  - [Nonsense-mediated mRNA decay in plants].

PMID- 21089640
TI  - [Quality control of ribosomal RNAs].

PMID- 21089641
TI  - [Collaboration of two kinds of tRNA/mRNA hybrids: trans-translation].

PMID- 21089642
TI  - [Regulation of RNA-binding proteins by MAPK signaling].

PMID- 21089643
TI  - [Regulation of translation initiation].

PMID- 21089644
TI  - [MRNA surveillance ].

PMID- 21089645
TI  - [Self or non-self RNA sensing mechanism of innate antiviral immunity].

PMID- 21089646
TI  - [Autoimmune diseases and RNA].

PMID- 21089647
TI  - [Aberrant pre-mRNA splicing in neurological disorders].

PMID- 21089648
TI  - [Oncogenic HMGA1a protein causes sporadic Alzheimer's disease-associated aberrant
      splicing].

PMID- 21089650
TI  - [An active contour model applied to vascular image segmentation].
AB  - In this paper is presented an active contour model applied to vascular image
      segmentation. This model can adaptively adjust the proportion of global and local
      intensity information in accord with the anastomosis status between local contour
      and boundaries. Our method is able to work effectively on segmentation of
      angiographic image with intensity inhomogeneity and noise. Compared with other
      methods, our method is not sensitive to initialization and it eliminates the need
      for manual adjustment of new parameter.

PMID- 21089649
TI  - [Brain functional connectivity in depression during emotion processing].
AB  - Cognitive and emotional dysfunction in depressed patients has been broadly
      researched. However, the physiological mechanism of the emotional impairment is
      still obscure. In this study, according to the ethical principles and the
      procedures of informed consent, we enrolled 16 depression patients and 16 normal
      subjects in a "learning-judgment" cognitive task. Emotional faces were chosen and
      used as the visual stimuli, while the subjects' scalp electroencephalographs
      (EEG) were recorded. We calculated the coherences of the event-related EEG
      signals between different functional brain regions and used the repeated measure
      analysis of variance (ANOVA) to analyze the coherences. The results revealed, (1)
      The depressed patients had a significantly lower inter-hemisphere coherence than
      did the normal controls at frontal sites across all EEG basic rhythms; (2) The
      inter-hemispheric coherence of EEG beta activity was significantly correlated
      with the emotional processing during 1-200 ms after stimulus onset, and the
      synchronicity with the negative emotion stimulus was higher than that with
      neutral and positive stimuli; (3) The main effect of race was found at delta and
      theta bands at about 401-600 ms after stimulus onset. Moreover, the connectivity
      of inter-hemisphere for own-race stimulus was stronger than that for other-race
      stimulus.

PMID- 21089651
TI  - [Design of broadband power divider in microwave hyperthermia system].
AB  - In clinical application of microwave hyperthermia, multi-applicators are often
      simultaneously required to irradiate the tumor because of its large volume or its
      deep location. Power divider separates the input microwave energy into equal, or
      unequal, energy to each applicator. In this paper, the design procedure for the
      three-section transmission-line transformer based one-to-two equal-split
      Wilkinson power divider is introduced. By impedance analysis on equivalent
      scheme, the design parameter of power divider is provided, and by simulation and
      optimization on Ansoft HFSS, a microstrip structure Wilkinson power divider
      operating frequency 2. 45 GHz is given. Measurement test results from network
      analyzer show that it has 25% bandwidth and good isolation in output with this
      structure. Besides, it is characterized by small size and easy processing. This
      power divider suits microwave hyperthermia.

PMID- 21089652
TI  - [Support vector machine based high intensity focused ultrasound beam lesion
      degree classification and recognition].
AB  - Ultrasound based tissue thermal lesion non-invasive detection is of great
      significance in high intensity focused ultrasound (HIFU) clinical application. In
      this paper, we propose a sub-pixel method to quantify the ultrasound image change
      caused by HIFU as correlation-distance. The support vector machine (SVM) was
      trained by using correlation distance as samples, and the recognition effect was
      tested. Results showed that sub-pixel cross-correlation vector field could
      reflect the ablation lesions position. SVM based classification method can
      recognize HIFU beam lesion degree effectively.

PMID- 21089653
TI  - [An image mosaic algorithm of pathological section based on feature points].
AB  - In this paper, an image mosaic algorithm based on feature points was proposed by
      making a study of the image mosaic methods and the characteristics of
      pathological image. Points of interest were firstly extracted by Moravec operator
      in this method, and the corresponding feature matches of the original images were
      achieved by correlation coefficient. The parameters of affine transformation were
      calculated by the matching feature points, and weighted average method was used
      to fuse images. The experimental results show that, as for the pathological image
      with translation and rotation, the algorithm can extract the matching feature
      points accurately and realize the image seamless mosaic.

PMID- 21089654
TI  - [Study of muscle path based on hermite function].
AB  - The architecture and dynamic properties of human muscles are very complex. So,
      most of the muscles are represented simply by straight-line or curve in
      musculoskeletal model. The straight-line and curve are called muscle paths. The
      representation of the muscle path plays a vital role in musculoskeletal model
      simulation such as the estimation of muscle force. Firstly, we create a black box
      with the muscle force on the bones as the output signal. Then based on the
      assumption that there is a muscle path plane (MPP) at any time during joint
      movement, we construct the space curve function of the muscle path during joint
      instantaneous movement by mathematical approaches. Finally, we calculate the
      lengths of the muscle paths and analyze the changes of them during elbow flexion.

PMID- 21089655
TI  - [Design and implementation of the platform for clustering analysis on acupuncture
      manipulation parameters].
AB  - Acupuncture manipulation is the pivotal factor for conferring clinical efficacy
      of acupuncture. By retrieving in the scientific research data base and acquiring
      the characteristics of acupuncture manipulation parameters, we studied the
      cluster-algorithm on parameter analyses and implemented clustering analysis of
      acupuncture manipulation parameters. Then we disclose the inherent method of
      needling. Thus, it can be used as a theoretical base for the studies on standard,
      normalization and quantification of the acupuncture manipulation parameter.

PMID- 21089656
TI  - [Hurst index based analysis of sinus arrhythmia and atrial arrhythmia].
AB  - This study sought to disclose whether Hurst index can be used as a criterion for
      distinguishing sinus and atrial arrhythmia signals. Normal sinus rhythm beats,
      atrial premature contraction (APC) beats, and sinus bradycardia (SBR) signals,
      were taken from the MIT-BIH standard database. Hurst index method was used to
      distinguish the two kinds of arrhythmia. The results showed that the Hurst
      exponents of three kinds of signals were larger than 0.5, but they were in
      different value region. The data indicated that the long-term relevant character
      was the best for normal signal, better for sinus bradycardia, and the worst for
      atrial premature beats. So Hurst index is a useful identification criterion for
      distinguishing sinus and atrial arrhythmia signals.

PMID- 21089657
TI  - [A technology research for diagnosis of mammographic masses based on content
      based image retrieval].
AB  - In order to assist doctors in making the diagnosis of mammographic masses, a
      method is proposed in this paper. Twenty-two features are extracted from each
      queried region of interest (ROI). A k-nearest neighbor (KNN) algorithm is used to
      retrieve similar images from database, and further calculate the mutual
      information (MI) between the queried image and the images which are in the
      retrieval results, so as to improve the retrieval performance. Finally, the
      scheme takes the first nine images with the highest MI scores as the final
      retrieval results. With the purpose of providing available decision-making
      information of diagnostic aids, we compare and analyze three calculating methods
      of decision index. The experiment results show that this method is better than
      the method using KNN only, and this method improves the accuracy of diagnosis
      effectively.

PMID- 21089658
TI  - [Research on respiration course of human at different postures by electrical
      impedance tomography].
AB  - In this paper, the respiration courses of human at different postures are
      reconstructed by electrical impedance tomography (EIT). Conjugate gradient least
      squares (CGLS) algorithm is applied to reconstruct the resistivity distribution
      during respiration courses, and the EIT images taken from human at flat lying,
      left lying, right lying, sitting and prone postures are reconstructed and
      compared. The relative changes of the resistivity in region of interest (ROI) are
      analyzed to evidence the influences caused by different postures. Results show
      that the changes in postures are the most influential factors for the
      reconstructions, and the EIT images vary with the postures. In human at flat
      lying posture, the left and right lungs have larger pulmonary ventilation volume
      simultaneously, and the EIT-measured data are of lower variability.

PMID- 21089659
TI  - [A study of impact on human brain by mental calculation based on principal
      components analysis].
AB  - This study was conducted to analyze the impact on human's left and right brain by
      mental calculation based on principal components analysis (PCA).
      Electroencephalogram (EEG) data were collected from twenty-one people before and
      during mental calculation. In each subject, we first calculated the PCA load of
      maximum principal component of the theta wave in four brain electrodes of the
      forehead, then we analyzed the relationship between mental calculating event and
      each brain electrode. From closing eye to relaxing event and to performing mental
      calculation event, it was shown that the weight of left head decreased and the
      weight of right head increased. These results indicate that mental calculation
      increases the workload on the right forehead, and on the right side of head
      obviously.

PMID- 21089660
TI  - [A novel analyzer of traditional Chinese medicines fingerprint].
AB  - The chromatographic fingerprint of traditional Chinese medicine is a way of
      comprehensive expression to show its complicated chemical composition. It is a
      generally-accepted method for analyzing the quality of traditional Chinese
      medicines. In this article, we address an analysis algorithm of traditional
      Chinese medicines fingerprint and its FPGA circuit method. With the use of a
      method based on combined GA training BP-NN, and by virtue of high-speed operation
      and parallel computing, the system is implemented successfully with FPGA which
      can be used in field control. The result shows that this is an efficient and
      superior method for use in the process of preparing raw Chinese medicines.

PMID- 21089661
TI  - [Ajax-based child growth monitoring chart automatic drawing].
AB  - As regards the application of community residents electronics health record
      system, there is a question of how to draw the child growth monitoring chart
      quickly and efficiently, which is also the focus of this research for enhancing
      residents experience in using the system. The system is combined with the current
      emerging Ajax and GDI+ technology. The client uses the pre-designed Ajax Manager
      status to deal with residents' request and send XMLHTTP request to the server.
      Sever responds to the request and makes use of GDI+ programming for
      implementation of rendering graphics and feedback. The system finally realizes
      child growth monitoring chart releasing on the Web.

PMID- 21089662
TI  - [On the segmentation of malignant halo in ultrasound images of breast tumor].
AB  - The method for segmenting malignant halo of malignant breast tumor in ultrasound
      image is useful in providing evidence for the differential diagnosis of breast
      tumor. In this respect, we adopt an improved anisotropic diffusion filtering
      method to preprocess the breast tumor ultrasound image, and then apply an
      improved LBF model with combination of Otsu and morphology methods to extract
      internal and external contours for obtaining malignant halo based on LBF model
      proposed by Li. We compare our data of malignant halo with doctor's manual
      sketched malignant halo, and make quantitative analysis. The result shows that
      the malignant halo segmented by the proposed methods in this paper is in
      accordance with the manual-sketched malignant halo.

PMID- 21089663
TI  - [Research in filter functionality settings of digital electrocardiograph].
AB  - Filter pass-band settings have impact not only on ECG output amplitude, but also
      on output signal wave-form of some types of digital electrocardiograph. Lower cut
      off frequency is decided by Wander filter setting for some types of digital
      electrocardiograph, and higher cut-off frequency is decided by muscle filter when
      muscle filter functionality is "on". We research into various filter settings'
      impact on the output of digital electrocardiograph and have discussions on the
      malfunctions found in digital electrocardiograph measurement.

PMID- 21089664
TI  - [Development of a digital cardiac pacemaker for animals and its application in
      medical research].
AB  - In this research and development project, we used the general microprocessor as a
      core to constitute the animal cardiac pacemaker in vitro. Control of the
      pacemaker's settings was carried out by transmitting parameters through a serial
      communication interface. Finally, our pacemaker reaches a satisfying test result
      in activating the cardiac outer membrane of the rabbits. Full digital pacemaker
      has high precision, good stability, and has an intuitive way to set parameters.
      Owing to its smaller size, lower cost, and easier mass production, the digital
      pacemaker is a good candidate to replace costly medical pacemakers for activating
      the animal's heart.

PMID- 21089665
TI  - [The cytoskeleton and immigration of laryngeal squamous carcinoma cell affected
      by Fascin-1 expression].
AB  - This study sought to detect the effect of Fascin-1 expression on the cytoskeleton
      and immigration of laryngeal squamous carcinoma cell. In the experiment, Fascin-1
      expression in Hep-2 cells was inhibited by small interfering RNA. The
      cytoskeleton of Hep-2 cells was observed with the use of laser scanning confocal
      fluorescence microscope. Millicell insert was applied to detect the immigration
      of Hep-2 cells in vitro. The results showed that the integrity of cytoskeleton in
      Hep-2 cells was broken with the down-regulation of Fascin-1 expression and the
      immigration ability was decreased significantly (P < 0.05). The inhibiting ratio
      of cell immigration was 44.6 +/- 6.3%. In conclusion, inhibition of Fascin-1
      expression in Hep-2 cells could break the integrity of cytoskeleton and decrease
      the ability of cellular immigration.

PMID- 21089666
TI  - [The virtual reality simulation research of China Mechanical Virtual Human based
      on the Creator/Vega].
AB  - The China Mechanical Virtual Human (CMVH) is a human musculoskeletal
      biomechanical simulation platform based on China Visible Human slice images; it
      has great realistic application significance. In this paper is introduced the
      construction method of CMVH 3D models. Then a simulation system solution based on
      Creator/Vega is put forward for the complex and gigantic data characteristics of
      the 3D models. At last, combined with MFC technology, the CMVH simulation system
      is developed and a running simulation scene is given. This paper provides a new
      way for the virtual reality application of CMVH.

PMID- 21089667
TI  - [Design of the multi-functional bone forceps characterized by gripping, bending
      and cutting].
AB  - We have designed a sort of multi-functional bone forceps for use as orthopedic
      surgical instruments to grip, bend and cut the spicula. It is labor-saving and
      easily installed. Its left and right clamp bodies are connected by a rivet to
      hold the spicula, and the pressure-regulating shank is connected with the clamp
      seat body at the right top of the clamp body by a rivet. It is used to curve the
      spicula. At an appropriate location on the pressure-regulating shank is a pin
      cutting chip. On the right body rotating disc-clamp, there is a rectangular open
      cutting groove to be in use for cutting the specula with the role of pin-cutting
      chip. Being characterized by the use of mechanical leverage, the manipulations of
      holding and bending are less arduous. After achieving the 90-degree bend, the
      operator can cut off the specula successfully. The operation is easy to perform
      and labor-saving; the forceps can further meet the actual clinical demand.

PMID- 21089668
TI  - [Preparation and properties of calcium polyphosphate-based composite scaffold for
      bone tissue engineering].
AB  - Calcium polyphosphate (CPP) is a new type of degradable material for bone repair,
      yet it is fragile and is not so controllable in regard to degradation. For
      increasing biological activity and close proximity to natural bone structure, in
      this experiment, we chose chitosan (CS) and its derivative carboxymethyl chitosan
      (CMC) as the extracellular matrix structure for the organic phase. Aldehyde
      sodium alginate (ADA) was used as natural cross-linker. The binary (CPP/CMC) and
      ternary (CPP/CMC/CS) composite scaffolds were prepared by the "multiple composite
      cross-linking method". The degradation laws of the two materials were
      investigated through the weight loss of scaffolds, the pH value of degradation
      solution, the compressive strength and the surface morphology characterization.
      The results showed that the composite scaffolds had good interface and the
      compressive strength increased greatly, but the organic phase of dual-phase
      composite scaffolds degraded quickly, while degradation controllability and
      mechanical properties of ternary composite scaffold were significantly improved.
      All the above findings show that the method of ternary complex scaffold
      preparation is useful for the design and preparation of bone tissue engineering
      materials.

PMID- 21089669
TI  - [Research on preparation and quality control of drug-carried poly lactic-co
      glycolic acid microbubble].
AB  - This research was aimed to develop the technique and formula for the preparation
      of stable and effective microbubbles containing hydrophilic drugs. We prepared EB
      PLGA microbubbles and evaluated its drug loading and burst release to choose the
      best technique and formula. The result of optimizing formula was W1/O (1:15), EB
      PLGA (0.04), PVA (5%). The burst release decreased after the addition of
      supplemental agent and the change of method for preparation. We concluded that
      the optimizing formula could elevate drug loading and decrease burst release
      obviously.

PMID- 21089670
TI  - [On the preparation and mechanical properties of PVA hydrogel bionic
      cartilage/bone composite artificial articular implants].
AB  - In view of the problems that conventional artificial cartilages have no
      bioactivity and are prone to peel off in repeated uses as a result of
      insufficient strength to bond with subchondral bone, we have designed and
      prepared a novel kind of PVA-BG composite hydrogel as bionic artificial articular
      cartilage/bone composite implants. The effects of processes and conditions of
      preparation on the mechanical properties of implant were explored. In addition,
      the relationships between compression strain rate, BG content, PVA hydrogels
      thickness and compressive tangent modulus were also explicated. We also analyzed
      the effects of cancellous bone aperture, BG and PVA content on the shear strength
      of bonding interface of artificial articular cartilage with cancellous bone.
      Meanwhile, the bonding interface of artificial articular cartilage and cancellous
      bone was characterized by scanning electron microscopy. It was revealed that the
      compressive modulus of composite implants was correspondingly increased with the
      adding of BG content and the augments of PVA hydrogel thickness. The compressive
      modulus and bonding interface were both related to the apertures of cancellous
      bone. The compressive modulus of composite implants was 1.6-2.23 MPa and the
      shear strength of bonding interface was 0.63-1.21 MPa. These results demonstrated
      that the connection between artificial articular cartilage and cancellous bone
      was adequately firm.

PMID- 21089671
TI  - [Research on fibrinogen adsorption and its transformation response in
      hemocompatibility].
AB  - In this research,enzyme linked immunoassay (ELISA) was used to assay the
      fibrinogen (FIG) adsorbed on the Ti-O films and on the low temperature isotropic
      carbon (LTIC) films which were planted in the femoral arteries of 6 mongrel dogs
      for six months, respectively. The Ti-O films were planted in the dogs' left
      femoral arteries; the LTIC films as controls were planted in the dogs' right
      femoral arteries. The contents adsorbed in these two kinds of films were examined
      by scanning electron microscopy (SEM). The quantities of FIG adhered or denatured
      on the Ti-O films or LTIC films determined by ELISA, and the platelets adhered on
      the two kinds of films examined by SEM were of significant difference between the
      two groups. In the blood vessel, the amount of FIG adhered on biomaterial was
      related to its component and construction. FIG released electron to the
      biomaterial and induced the unfolding of C term of the gamma-chain of FIG, and
      the conjugation point and effect point were exposed. In conclusion, the
      biomaterial, which has the capability for resisting the electron release from FIG
      as well as for maintaining the invariable electric condition, will have excellent
      hemocompatibility.

PMID- 21089672
TI  - [Effects of superoxide dismutase on the periapical periodontitis in rat].
AB  - The purpose of this investigation was to elucidate the effects of superoxide
      dismutase (SOD) on the induced periapical periodontitis in rat, and to shed light
      on the possible mechanism involved in root canal therapy. 48 Wistar rats with
      induced periapical periodontitis were randomly divided into 3 groups; their root
      canals of molar teeth were prepared; and the root canals were filled with SOD,
      CH, and nothing, respectively. At 1, 2, 3 and 5 weeks after operation, 4 animals
      were killed respectively. Periapical roentgenogram and periapical pathological
      slices were made. The results were analyzed statistically by F test and t test
      with SPSS12.0 software package. After root canal therapy, mild inflammatory
      infiltration was observed in SOD and CH groups at 1 week. At 2 weeks, periapical
      periodontitis was improved. After 3 weeks, there was no inflammatory cell
      observed in SOD/CH group. At 3 and 5 weeks, no significant difference in
      periapical radiographic findings was noted between the experimental groups and
      normal group (P > 0.05). The periapical radiographic lesion in control group was
      larger than that in SOD and CH groups (P < 0.01). The results showed that SOD
      could control periapical inflammation and induce the proliferation of dentin and
      cementum. Therefore, SOD might be an ideal biocompatible material for root canal
      therapy.

PMID- 21089673
TI  - [Degradable performance and bio-mineralization function of PLA-PEG-PLA/PLA tissue
      engineering scaffold in vitro and in vivo].
AB  - The degradable performance and bio-mineralization function of PLA-PEG-PLA/PLA
      tissue engineering scaffolds in vitro and in vivo were systematically studied.
      The X-ray diffraction and Fourier transform infrared spectra showed that there
      was the deposition of bone-like carbonate hydroxyapatite on the surface of
      scaffolds. We found that the weight of scaffolds did not always decrease with the
      prolongation of time in vitro. At the same time, we found that after the PLA-PEG
      PLA/PLA tissue engineering scaffolds were embedded in skulls of rhesus monkeys,
      the new bone area reached 75% at the 12th week. Histological observation showed
      that the new bones were rebuilt and knitted bones were formed at the 12th week.
      These findings meant that the PLA-PEG-PLA/PLA tissue engineering scaffolds were
      potential in clinical use.

PMID- 21089674
TI  - [Construction and expression of repeats of HER-2 mimetic peptide].
AB  - To produce many epitopes of peptide mut, different tandem repeats containing HER
      2 mimetic peptide mut were constructed and expressed. The oligonucleotide coding
      mut sequence was inserted into pET28a(+) to construct the prokaryotic recombinant
      plasmid pET28a-mutl. The mut coding sequence was repeatedly inserted into the
      vector in tandem to obtain a series of plasmids pET28a-mut2, pET28a-mut4, pET28a
      mut8 and pET28a-mut16. The plasmids were transformed into E. coli. BL21 and
      induced by IPTG. The recombinant proteins were expressed in E. coli. The binding
      analysis verified that the interaction between the tandem peptides mut and
      Herceptin was increased. In conclusion, the tandem peptides consisted of many
      antigen epitopes, and laid the foundation for the further study of HER-2 peptide
      vaccine for biotherapy of cancer with HER-2 overexpression.

PMID- 21089675
TI  - [Radioiodide treatment mediated by adenovirus transfer of human sodium iodide
      symporter gene into androgen-independent prostate cancer].
AB  - This study sought to probe the feasibility of instituting a radioiodide treatment
      for androgen-independent prostate cancer by adenovirus transfer of the hNIS gene.
      A recombinant adenovirus, Ad-CMV-NIS, that expressed the NIS gene under the
      control of cytomegalovirus (CMV) promoter was constructed. In vitro, after
      infection with Ad-CMV-NIS,PC-3 prostate cancer cells exhibited an uptake of
      perchlorate-sensitive iodide, approximately 120 times higher than that exhibited
      by negative control Ad-CMV-GFP-infected cells. The half-time of efflux was 26.6
      min. Clonogenic assays demonstrated that Ad-CMV-NIS-infected cancer cells were
      selectively killed by exposure to 131I. In vivo, Ad-CMV-NIS infected tumors
      showed significant radioiodine accumulation (16.30 +/- 8.72)% ID/g at 2h
      postinjection) with an effective half-life of 5.4h. The tumor could be clearly
      visualized by 131I scintigraphy. These data indicate that infection with Ad-CMV
      NIS is an efficient way to induce radioiodide uptake in vitro and in vivo, thus
      suggesting that NIS-based gene therapy has the potential for use in androgen
      independent prostate cancer.

PMID- 21089676
TI  - [The isolation and assessment of Golgi apparatus from gastric cancer cells
      SGC7901].
AB  - The Golgi complex is the central organelle of the secretory pathway and has many
      complicate functions. The endeavours to isolate and purify the Golgi apparatus
      from cultured cells will benefit further investigation of Golgi. A large number
      of gastric cancer cells SGC7901 were cultivated in vitro, then Golgi apparatus
      were isolated from the cells by differential centrifugation combined with sucrose
      density gradient ultra-centrifugation. Its purity was characterized biochemically
      by enzymatic assays, morphologically by electron microscopy (EM) and neutral red
      supravital staining. Finally the Golgi complex was successfully fractionated from
      gastric cancer cells SGC7901. The first successful isolation of Golgi apparatus
      from gastric cancer cells SGC7901 by using ultra-centrifugation will lead to
      research into the function of Golgi apparatus.

PMID- 21089677
TI  - [Association of HLA-A0205 and HLA-A30 with latent autoimmune diabetes in adults].
AB  - To investigate the association of HLA-A0205 and HLA-A30 with latent autoimmune
      diabetes mellius in adults (LADA) in Chengdu Hans, 121 subjects (41 cases of
      LADA, 40 cases of T2DM, and 40 normal controls) were enrolled in the study. The
      frequencies of HLA-A0205 and HLA-A30 were determined by nested PCR-SSP and direct
      sequencing, respectively. The allele frequencies of patient groups and of normal
      controls were compared by chi-square test using SPSS 11.0 (alpha = 0.05). Hardy
      Weinberg equilibrium was tested with use of software HWE (alpha = 0.05). Data
      from the subjects showed: HLA-A0205 was present in 1 patient with LADA and in 1
      normal control (2.44% and 2.5%, respectively), HLA-A30 was present in 2 patients
      with LADA, in 2 patients with T2DM and in 1 normal control (4.87%, 5.0% and 2.5%,
      respectively). There was no statistically significant difference between the
      allele frequencies of the three groups. These results suggest that HLA-A0205, HLA
      A30 may not be related to LADA in Chengdu Hans. Yet, further studies with larger
      sample size may be needed to warrant this conclusion.

PMID- 21089678
TI  - [Initial observation of oxygen carriers with acute myocardial infarction in
      rats].
AB  - The purpose of this study was to test whether oxygen carriers could decrease
      tissue injury in a rat model of acute myocardial infarct. The study included 3
      groups: SD rats in group II and group III were subjected to permanent occlusion
      of their left anterior descending coronary arteries; SD rats in group I were
      subjected to sham-operation. The success of modeling was assartained by ECG. Then
      the rats were given drug via caudal veins for 2 days. A quantitative evaluation
      was made with an automatic device for interpretation of cardiac troponin T
      (cTnT); heart staining was made for the calculation of myocardial infarction size
      (MIS); and myocardial tissue was taken and subjected to routine pathological
      hematoxylin-eosin (HE) staining for showing myocardial cell injury. cTnT in the
      sham-operation group was significantly lower by comparison with that in the model
      group (P < 0.01), and it was slightly lower in the oxygen carriers group than
      that in the model group, but there was no statistically significant difference (P
      = 0.18); MIS was significantly smaller in the sham-operation group than that in
      the model group (P < 0.01), and it was greater in the model rats than that in the
      oxygen carriers rats (P < 0.05). HE staining of myocardicum in the oxygen
      carriers group was significantly better than that in the model group (P < 0.01).
      The evidence suggested that oxygen carriers increased oxygen supply to ischemic
      myocardium, reduced the myocardial injury, and thus might offer a novel treatment
      of myocardial infarction.

PMID- 21089679
TI  - [Construction and selection of effective mouse Smad6 recombinant lenti-virus
      interference vectors].
AB  - This experiment was designed to construct mouse Smad6 recombinant RNA
      interference vectors and determine their interference effects on bone marrow
      mesenchymal stem cells (BMSCs). Three recombinant Smad6 RNA interference vectors
      were constructed by molecular clone techniques with a lenti-virus vector
      expressing green fluorescent protein (GFP), and the correctness of recombinant
      vectors was verified by DNA sequencing. Mouse BMSCs were used for transfection
      experiments and BMP-2 was in use for osteogenic induction of MSCs. The
      transfection efficiency of recombinant vectors was examined by Laser confocal
      scanning microscope and the interference effect of recombinant vectors on Smad6
      gene expression was determined by real-time RT-PCR and Western blot,
      respectively. Three Smad6 recombinant RNA interference vectors were successfully
      constructed and their correctness was proved by DNA sequencing. After
      transfection, GFPs were effectively expressed in MSCs and all of three
      recombinant vectors gained high transfection efficiency (> 95%). Both real-time
      PCR and Western blot examination indicated that among three recombinant vectors,
      No. 2 Svector had the best interference effect and the interference effect was
      nearly 91% at protein level. In conclusion, Mouse recombinant Smad6 RNA
      interference (RNAi) vector was successfully constructed and it provided an
      effective tool for further studies on BMP signal pathways.

PMID- 21089680
TI  - [Effect of combined use of PDTC and paclitaxel on proliferation and invasion of
      human breast cancer cell line MCF-7].
AB  - This investigation was made with special reference to the effect of the combined
      use of nuclear factor-kappaB (NF-kappaB) inhibitor Pyrrolidine
      dithiocarbamate(PDTC) and Paclitaxel on the expression of Matrix
      metalloproteinases (MMP-9) and its inhibitor TIMP-1, and on the proliferation and
      invasion of human breast cancer cell line MCF-7. The MCF-7 cells were treated
      with PDTC and Paclitaxel. The effect on proliferation was evaluated by MTT assay.
      The cell cycle was analyzed by flow cytometry. Western blot was used to determine
      the change of NF-kappaB p65, MMP-9 and TIMP-1 expression in MCF-7 cells after
      treatment. RT-PCR was used to detect NF-kappaB p65 mRNA expression. The invasion
      ability of MCF-7 cells was tested by the invasion, migration and cell adhesion
      assay. The cell growth was significantly slowed down and the cell cycle was
      arrested at G0/G1 phase after the combined treatment. The expression of NF-kappaB
      p65 and MMP-9 was down-regulated and the invasion ability of MCF-7 cells was
      decreased after the combined treatment. In conclusion,PDTC combined with
      paclitaxel effectively inhibited cell proliferation, induced cell cycle arrest,
      and decreased cell invasion ability of breast cancer MCF-7 cells. The mechanism
      may be associated with the inhibiting effect of PDTC on the NF-kappaB-related
      gene expression.

PMID- 21089681
TI  - [Study of metabolic syndrome and insulin secretion function in first-degree
      relatives of type 2 diabetic patients in a large cohort study in Sichuan province
      of China].
AB  - This investigation was directed to the metabolic syndrome and the islet beta-cell
      secretory function in the first-degree relatives (FDR) of type 2 diabetic
      patients in Sichuan province. A large cohort study was designed. Totally 1929
      subjects were investigated. They were in two groups: FDR group comprising 505
      first-degree relatives of type 2 diabetic patients, and Control group comprising
      1424 controls without positive family history of Diabetes. Blood pressure,
      weight, waist, plasma glucose, lipids and insulin were measured. HOMA-IR and HOMA
      beta indexes were used to evaluate insulin resistance and beta-cell secretion
      function. The insulin sensitivity index (ISI) and glucose disposition index (DI)
      were also used to evaluate insulin resistance. After adjustment for age and sex,
      HOMA-IR increased, ISI, DI and HOMA-beta decreased in FDR group when compared
      with controls (P < 0.05). The incidence of co-existed three or more metabolic
      disorders and metabolic syndrome was higher in FDR group than that in control
      group (P < 0.05). In FDR group, HOMA-IR increased, HOMA-beta, DI and ISI
      decreased while the number of co-existing metabolic disorders increased. But when
      the number of co-existing metabolic disorders > or = 4, HOMA-IR increased no
      longer and ISI decreased no more. Metabolic disorders occurred more frequently in
      FDR of diabetic patients than those in individuals without positive family
      history. As the number of co-existing metabolic disorders increased, the beta
      cell secretion function and insulin sensitivity became worse. Our study indicated
      that it is necessary to keep on monitoring the metabolic index in FDR of type 2
      diabetes and provide early preventive interventions.

PMID- 21089682
TI  - [Segmentation of vascular intima ultrasound images based on an improved C-V
      model].
AB  - In view of the fact that blood vessels can reflect, to a certain degree, the
      pathologic changes of cardiovascular diseases, research workers count it
      necessary to take quick and accurate segmentation of neointimal ultrasound
      images. The segmentation is faster owing to the reconciled signed distance
      function added into the classical C-V mode, thus avoiding the step of re
      initialization. Moreover, the curve evolution is controlled by external energy
      item. The displacement of boundary points is calculated. The result shows that
      the improved model can effectively and accurately extract the contour of
      neointimal ultrasound images. The curve can not only assess the extracted
      boundary but also reflect the abnormality of vascular or cardiac rhythm.

PMID- 21089683
TI  - [A new method of eliminating motion artifacts in DSA].
AB  - In digital subtraction angiography (DSA), the contrast of the vessels is greatly
      improved with the injection of contrast medium. In addition, more clear vessels
      can be visualized by eliminating the images of non-vessel organs, and those
      images are called subtraction image or DSA. Therefore, DSA is of wide use for
      diagnosis of cardiovascular disease. Subtraction of images obtained before and
      after injection of contrast medium may create motion artifacts due to the
      aspiration of patients. In this regard, being motivated by the doctors'
      experience that the displacement of diaphragm can be used as the reference to
      measure the heart beat, we present a method to eliminate the motion artifacts. In
      our method, firstly, a set of DSA images are taken before injection of contrast
      medium, which are called "mask images"; and one image taken after injection of
      contrast is called "target image". Secondly, a "reference mask image" is
      assigned, which is one of "mask images"; "and the displacement of diaphragm from
      "reference mask image" to the other mask images and the target contrast image is
      measured. Thirdly, based on the measurement results, several candidate mask
      images in which the displacement is less than a threshold can be selected. At
      last, the optimization algorithm is applied on the selected images, and the
      corresponding mask image that has minimum motion artifact is retrieved.

PMID- 21089684
TI  - [Focusing properties of picosecond electric pulses in non-invasive cancer
      treatment].
AB  - In the light of optical theory, we advanc an ultra-wideband impulse radiating
      antenna (IRA) which is composed of an ellipsoidal reflector and a cone radiator.
      The high-intensity ultra-short electric pulses radiated by IRA can be transferred
      into the deep target in tissue non-invasively and be focused effectively. With
      the focused picosecond electric pulses, the organelles (mitochondria)
      transmembrane potential shall change to collapse under which the tumor cells will
      be targetly induced to apoptosis, so the method of non-invasive treatment of
      tumors would be achieved. Based on the time-domain electromagnetic field theory,
      the propagation characteristics of picosecond electric pulses were analyzed with
      and without the context of biological tissue, respectively. The results show that
      the impulse characteristics of input pulse were maintained and the picosecond
      electric pulses can keep high resolution in target areas. Meanwhile, because of
      the dispersive nature of medium, the pulse amplitude of the pulses will attenuate
      and the pulse width will be broadened.

PMID- 21089685
TI  - [Research on flow characteristics in a non-blade centrifugal blood pump based on
      CFD technology].
AB  - The problem of thrombus and hemolysis in blood pump has always been an important
      topic to study in the development of the blood pump. Numbers of research results
      show that it is the complicated flow and the high shear stress of the mechanical
      movement that result in the thrombus and hemolysis. In this study, with the
      cooperation of Shanghai Children's Medical Center, we have used computational
      fluid dynamics (CFD) commercial software FLUENT to compute and analyze the flow
      characteristics in a non-blade centrifugal blood pump. The results figure out
      that this pump has a reasonable flow distribution and the shear stress
      distribution is under the critical broken state of red blood cell; meanwhile,
      there is less thrombus and hemolysis in this pump. So it is in the foreground for
      clinical use.

PMID- 21089686
TI  - [Role of 6% hydroxyethylstarch 130/0.4 and furosemide in the treatment of acute
      pancreatitis].
AB  - This study was conducted to observe the effects of intravenously administered 6%
      hydroxyethylstarch 130/ 0.4 solution and furosemide on the outcome of acute
      pancreatitis patients. Patients admitted to our center from October 16, 2007
      through August 31, 2009 were given intravenous infusions of 6% hydroxyethylstarch
      130/0. 4 solution (1 000-2 000 ml administered for an adult) soon after
      admission. At the same time, furosemide was administered as intravenous bolus,
      trying to maintain a fluid balance. The dose level of hydroxyethylstarch was
      gradually lowered from the second day after admission. A total of 135 patients
      (54% of patients with a Ranson's score > or = 3 and 61% with a Balthazar CT score
      > or = D) were treated with our protocol. Only 4% and 7% patients developed
      pancreatic and systemic complications respectively; only 1 patient underwent
      necrosectomy. The in-hospital mortality rate was 4%. It was estimated that, on
      the average, 18. 3% of blood volume was lost on admission. Our study suggest that
      intravenously administered 6% hydroxyethylstarch 130/0. 4 solution and furosemide
      might be beneficial for patients with acute pancreatitis. Plasma extravasation is
      a central event of acute pancreatitis. The reversal of hypovolemia is crucial for
      the success in treatment of acute pancreatitis.

PMID- 21089687
TI  - [Research on a special model of nerve impulse propagation].
AB  - Hodgkin-Huxley (HH) nerve model is a famous model which is used to describe nerve
      impulse propagation in nerve fibre. FitzHugh-Nagumo (FHN) model is a
      simplification of HH model, and Huxley equation is a special case of FHN
      equation. It has been shown that Huxley equation possesses the basic
      characteristics of nerve model. Researching on these models was often carried out
      in virtue of numerical techniques in the past. And, in so for as is known, an
      efficient and simple method which can be used to obtain analytic solutions is
      lacking. Yet, a qualitative analysis on Huxley equation's traveling system has
      been carried through in this paper. There is a bounded heteroclinic orbit having
      its one end in connection with a saddle point for the traveling wave system. Then
      a linear plane autonomous system whose singular point is a saddle point is
      chosen. By means of the system orbit vector's slope, and according to homogeneous
      balance principle, the traveling wave solutions of Huxley equation's traveling
      system are constructed. The method used here is called LS method.

PMID- 21089688
TI  - [On predicting the T cell and B cell epitopes of platelet membrane glycoprotein
      II b/ III a antibody from human and mice].
AB  - HLA-A * 0201, HLA-A * 1101, and HLA-A * 2401 CTL restricted epitopes of platelet
      membrane glycoprotein II b/III a antibody of human and mice were predicted by use
      of SYFPEITHI, RANKPEP, BIMAS, SVMHC, PREDEP, MHCPRED, and PROPRED predictive
      programs. In the results, the peptides (found in HLAPRED) that can lead to
      autoimmune disease and have been published were removed; and the epitopes of HLA
      A * 0201 must cover the epitopes of HLA-A * 1101 and HLA-A * 2401 being combined
      to predTAP and TAPPred for predicting the binding affinity of peptides toward the
      TAP transporter and NetChop, MAPPP, PAProc for predicting cleavages; HLA-DR Th
      restricted epitopes of GPII b/III a antibody were predicted by SYFPEITHI,
      RANKPEP, MHCPRED, and HLAPRED, after removal of the peptides (found in HLAPRED)
      that can lead to autoimmune disease and have been published, the Th epitopes must
      cover the CTL mixed epitopes as being stated above. The secondary structure,
      hydrophobic regions, flexibility, surface probability and the B cell epitope were
      predicted by using various methods. Ten mixed peptides of T cell epitopes were
      selected from more than 1 740 peptides. They were located at the aa9-115, aa24
      38, aa50-64, aa65-81, aa109-121 of anti-GP II b/III a-Human and the aal-15, aa26
      40, aa46-60, aa68-82, aa93-107 of anti-GP II b/III a-Mice. B cell epitopes of
      anti-GP II b/III a-Human might locate at aa5-9, aa22-30, aa40-46, aa55-71, aa80
      90, aa100-105, aa110-115; and the epitopes of anti-GP II b/III a-Human might
      locate at aa5-10, aa38-43, aa58-70, aa77-84, and aa99-105.

PMID- 21089689
TI  - [Applications of fluorescent molecular imaging in tumor detection].
AB  - As a recently emerging molecular imaging technique, fluorescent molecular imaging
      has the advantage of fast imaging, simple operation, high sensitivity, low cost,
      nonionizing radiation and so on. Through the real-time, non-invasive, specific
      tracking and detection of tumorigenesis, metastases, angiogenesis, and the
      therapeutic response to antitumor drugs in vivo, we can study the physiological
      and pathological processes within tumors at cellular and molecular levels.
      Fluorescent molecular imaging provides effective methods for the early detection
      and targeted therapy of tumor, for the intraoperative visualization of tumor
      foci, as well as for the development of new antitumor drugs in the future
      clinical practice.

PMID- 21089690
TI  - [Histocompatibility and imprinting status of parthenogenetic embryonic stem
      cells].
AB  - The parthenogenetic embryonic stem cells (pESCs) derived from parthenogenetic
      embryos have the totipotency and proliferation capacity similar to those of the
      fertilized embryonic stem cells (fESCs). Therefore, the establishment of pESCs
      line avoids destroy of embryo and kence may make pESCs less concerns with
      political and ethical issues. These cells are characterized by their
      histocompatibility with the oocyte donor and therefore is more suitable for cell
      and tissue replacement therapy. In addition, because of the typical imprinting
      status, pESCs also provide a valuable in vitro model system for studying the
      molecular mechanisms in genomic imprinting.

PMID- 21089691
TI  - [Progress of molecular imaging research on the use of RNA interference in
      malignant tumors].
AB  - RNA interference (RNAi) is applied in the gene therapy of malignant tumors as an
      effective technique to degrade its homologous mRNA specifically. This technique
      has been developed quickly in broad prospects. Molecular imaging plays an
      important role both in gene imaging and in molecular signal transduction. It is
      used as a direct approach to study the onset and development of disease. The
      technique of RNAi can be used for preparing molecular probes, for making earlier
      and specific diagnosis, and for targeted gene therapy of malignant tumors.

PMID- 21089692
TI  - [Gene function enrichment analysis of microarray data].
AB  - Microarray data analysis is a very critical step and it is currently facing a
      major challenge to dig out research-related information and provide professional
      interpretation. Gene function enrichment analysis appears to address the
      bottleneck issue with reasonable option. This article focuses on the principle,
      the relevant analytical tools and applications of gene function enrichment
      analysis, thus further laying the foundation for a wide range of applications.

PMID- 21089693
TI  - [The research progress of breast ultrasound CAD with breast imaging and reporting
      data system].
AB  - Ultrasound imaging is a valuable tool in the detection of breast lesions, and the
      breast imaging and reporting data system (BI-RADS) guides the ultrasound
      diagnosis of breast lesion to improve the diagnosis accuracy. The research of
      breast ultrasound computer-aided diagnosis (CAD) with BI-RADS-US is a hot topic
      now. In this paper, we reviewed the research progress of breast ultrasound CAD
      with BI-RADS-US, summarized the present problems, and discussed the future
      development.

PMID- 21089694
TI  - [Research on biomechanics properties of occipito-atlantoaxial complex by finite
      element method].
AB  - Based on the research history of the biomechanics of occipito-atlantoaxial
      complex, we have systematically summarized the use of finite element method for
      studying biomechanics of occipito-atlantoaxial complex. Then, combined with four
      basic principles of establishing an effective finite element model for mechanics,
      our comments are focused on the establishment of geometrical model, finite
      element model, finite element mechanics model, and on the method and
      implementation for validating the model. In addition, the developing trends,
      existing problems and future researching directions in this area are discussed.

PMID- 21089695
TI  - [A review of automatic particle recognition in Cryo-EM images].
AB  - Advances in cryo-electron microscopy (Cryo-EM) and single-particle reconstruction
      have led to increasingly high resolutions of macromolecular three-dimensional
      reconstruction. However, for keeping up the continuing improvements in
      resolution, it is necessary to increase the number of particles included in
      performing reconstructions. Manual selection of particles, even assisted by
      computer, is a bottleneck of single-particle reconstruction. Cryo-EM image has
      low signal-to-noise ratio and low contrast, which leads to difficulty in particle
      picking. Various approaches have been developed to address the problem of
      automatic particle. This paper describes the application of template-based
      method, edge based method, feature-based method, neural network, DoG-based and
      simulated annealing approach in particle picking. The characteristics of various
      approaches are discussed, and the future development is presented.

PMID- 21089696
TI  - [Advancement of studies on ALDH1 as a universal marker of stem cells].
AB  - Aldehyde dehydrogenase 1 (ALDH1, ALDH1A1 or RALDH1), an enzyme responsible for
      the oxidation of intracellular aldehydes, was shown to have a function in the
      early differentiation of stem cells. Its activity shows promising potential as a
      universal marker for the identification and isolation of normal stem cells and
      cancer stem cells from multiple sources in a variety of tissue types. Herein, we
      review the available data reporting the utilization of ALDH1 activity as a means
      to identify and isolate normal stem cells and cancer stem cells (CSCs), and the
      potential diagnostic and therapeutic implications, with a special focus on the
      mammary gland and breast cancer. The research opportunity in this area of
      interest is emphasized.

PMID- 21089697
TI  - [Advances in research on radioiodine therapy of carcinoma mediated by gene
      transfer technology].
AB  - Radioiodine therapy of carcinoma could be mediated by transferring the genes
      which participate in the process of iodine metabolism in thyroid. The correlative
      genes are sodium/iodine symporter gene, thyroid peroxidase gene and the specific
      thyroid transcription factors, and others. The objective gene can specifically
      express in carcinoma by inserting the tissue-specific promoter/enhancer upstream
      of them, so radioiodine could be used to treat varied carcinomas. The radioiodine
      uptake in carcinoma cells was obviously increased and the radioiodine therapy of
      carcinoma was effective after those genes had expressed in carcinoma cells. The
      main problem was that the effective half-time of radioiodine in cells was too
      short to produce the ideal effect of radioiodine therapy. Moreover, 211At and
      188Re could be transferred by sodium/iodine symporter and they could be used to
      treat the carcinoma that is capable of radioiodine uptake.

PMID- 21089698
TI  - [Progress in repair of sciatic nerve injury by bone marrow mesenchymal stem
      cells].
AB  - Bone marrow mesenchymal stem cells (BMSCs) possess the potential of self
      duplication, multi-directional differentiation, and also the ability to
      differentiate (in the direction of ectoderm) into neuron and neuroglial cells in
      vitro as well as to promote the reparation of sciatic nerve injury in vivo,
      especially for the reparation of the long-segment nerve. Progress in repair of
      sciatic nerve injury by BMSCs has been reviewed in this article.

PMID- 21089699
TI  - Childhood immunizations.

PMID- 21089700
TI  - Measuring chemicals in humans: state biomonitoring policies.

PMID- 21089701
TI  - The concentration of antibiotic in fresh-frozen bone graft.
AB  - We investigated the antibiotic concentration in fresh-frozen femoral head
      allografts harvested from two groups of living donors. Ten samples were collected
      from patients with osteoarthritis of the hip and ten from those with a fracture
      of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was
      administered as a pre-operative prophylactic antibiotic. After storage at -80
      degrees C for two weeks the pattern of release of cefazolin from morsellised
      femoral heads was evaluated by an in vitro broth elution assay using high
      performance liquid chromatography. The bioactivity of the bone was further
      determined with an agar disc diffusion and standardised tube dilution bioassay.
      The results indicated that the fresh-frozen femoral heads contained cefazolin.
      The morsellised bone released cefazolin for up to four days. The concentration of
      cefazolin was significantly higher in the heads from patients with osteoarthritis
      of the hip than in those with a fracture.Also, in bioassays the bone showed
      inhibitory effects against bacteria.We concluded that allografts of morsellised
      bone from the femoral head harvested from patients undergoing arthroplasty of the
      hip contained cefazolin, which had been administered pre-operatively and they
      exhibited inhibitory effects against bacteria in vitro.

PMID- 21089703
TI  - Nursing needs a new image.

PMID- 21089702
TI  - The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro
      study.
AB  - Various chemicals are commonly used as adjuvant treatment to surgery for giant
      cell tumour (GCT) of bone. The comparative effect of these solutions on the cells
      of GCT is not known. In this study we evaluated the cytotoxic effect of sterile
      water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H(2)O(2)) and 50% zinc
      chloride (ZnCI(2)) on GCT monolayer tumour cultures which were established from
      six patients. The DNA content, the metabolic activity and the viability of the
      cultured samples of tumour cells were assessed at various times up to 120 hours
      after their exposure to these solutions. Equal cytotoxicity to the GCT monolayer
      culture was observed for 95% ethanol, 5% phenol, 3% H(2)O(2) and 50% ZnCI(2). The
      treated samples showed significant reductions in DNA content and metabolic
      activity 24 hours after treatment and this was sustained for up to 120 hours. The
      samples treated with sterile water showed an initial decline in DNA content and
      viability 24 hours after treatment, but the surviving cells were viable and had
      proliferated. No multinucleated cell formation was seen in these cultures. These
      results suggest that the use of chemical adjuvants other than water could help
      improve local control in the treatment of GCT of bone.

PMID- 21089704
TI  - Extending the reach of nursing knowledge and innovation.

PMID- 21089705
TI  - PhD Away Days: a component of PhD supervision.
AB  - AIM: This paper describes a peer-to-peer and supervisor support and mentoring
      process that was implemented in one PhD programme in nursing in the Republic of
      Ireland. BACKGROUND: PhD Away Days are held once per year and attended by all
      enrolled PhD students and their academic supervisors. Positive evaluations were
      obtained both from students and supervisors as collective learning occurred and
      group cohesiveness developed. All participants expressed interest in continuing
      the PhD Away Days as they learned from others' experiences. In addition, the
      range of topics provided learning on topics of concern across content areas, e.g.
      conceptual and theoretical developments, research design, challenges in data
      collection, and analysis and publication plans. Most importantly, there was a
      feeling of togetherness among students, thus decreasing the feeling of being
      alone with the challenges of PhD work. CONCLUSIONS: Plans for the future include
      the need to have the PhD Away Days continued structured around key topics of
      concern to both students and supervisors, and to implement content-specific
      modules in the PhD programme.

PMID- 21089706
TI  - Imitative suicide: an issue for psychiatric and mental health nursing?

PMID- 21089707
TI  - Implementation of Clubhouse Model programme: perception of mental health nurses.

PMID- 21089708
TI  - Physiotherapist involvement and views on the application of physical intervention
      to manage aggression: data from a national survey.

PMID- 21089709
TI  - A follow-up report on preventing suicide: focus on medical/surgical units and the
      emergency department.

PMID- 21089710
TI  - [Research and development strategy of agents for the treatment of metabolic
      diseases].

PMID- 21089711
TI  - Reclutamento alveolare in sala parto: la sustained lung inflation. (Alveolar
      recruitment in the delivery room: sustained lung inflation).
AB  - At birth the transition by the fetal situation to neonatal life occurs. The real
      mechanism of lung liquid reabsorption and lung aereation at birth, in the past
      attributed only to the epithelial sodium channel function, has recently been
      linked to the first important breaths too and to the following changes in
      transpulmonary pressure. If this quite easily happens in the term baby, the
      preterm infants and all the babies with poor respiratory effort may have a
      delayed achievement of an adequate functional residual capacity (FRC). Premature
      delivery is always associated to the failure of respiratory transition and
      preterm babies frequently need a respiratory support (e.g., N-CPAP). Actual
      recommendations do not consider to mimic the physiologic changes that usually
      happen to the term neonate at birth. The application at birth of the sustained
      lung inflation (SLI) (a peak pressure of 25-30 cm H2O for 10-20 seconds), with
      nasopharyngeal tube or an adequately sized mask and a Neo-puff device, followed
      by the application of a continuous adequate PEEP (e.g., 5 cmH2O) is effective in
      the achievement of the FRC in animal studies and in the reduction of the need of
      mechanical ventilation (MV) in preterm infants at risk for RDS. Large RCTs are
      needed to verify the real efficacy of SLI in the delivery room to prevent the
      need of mechanical ventilation and to improve respiratory outcomes of preterm
      infants at risk for RDS.

PMID- 21089712
TI  - Risk factors for INSURE failure in preterm infants.
AB  - The INSURE (Intubation-surfactant-extubation) method has been found to reduce the
      need for MV, the duration of respiratory support, and the need for surfactant in
      preterm infants with respiratory distress syndrome (RDS). However, this method
      fails in some patients. We demonstrated that a birth weight <750 g, pO2/FiO2
      <218, and a/ApO2 < 0.44 at the first blood gas analysis were independent risk
      factor for INSURE failure in infants with gestational age <30 weeks. Moreover, we
      demonstrated that INSURE treatment can be repeated being the respiratory outcome
      similar in infants treated with single or multiple INSURE procedures. Thus, it is
      possible that the multiple INSURE strategy might decrease the failure rate of
      INSURE and increase its effectiveness in preventing the need for mechanical
      ventilation (MV).

PMID- 21089713
TI  - Circulating endothelial progenitor cells and diseases of the preterm infant.
AB  - During the last decade, multiple techniques have been developed to isolate and
      quantify human endothelial progenitor cells (EPCs). In parallel, a number of
      studies have applied these methodologies to investigate the number and function
      of circulating EPCs in adult diseases characterized by vascular dysfunction.
      However, very little is known about different subtypes of EPCs during gestation,
      during the neonatal age or in neonatal diseases. Initial evidence supports the
      hypothesis that circulating angiogenic cells may play an important role during
      development, and attention has particularly focused in clarifying the function of
      EPCs in lung vascular development, and the role of the impairment of EPC
      mobilization and homing in hyperoxia-induced lung injury characteristic of
      bronchopulmonary dysplasia. Among different subtypes of EPCs, both the role of
      angiogenic mononuclear cells (triple-positive CD34+CD133+VEGFR-2+ cells and
      colony forming unit-Hill cells) and endothelial colony forming cells (ECFCs) in
      physiological vascular development and during neonatal diseases need to be
      elucidated. A better understanding of EPC biology during gestation, during the
      neonatal age and in preterm infants will unravel the pathologic basis of
      bronchopulmonary dysplasia and other preterm and term neonatal diseases
      characterized by a prominent defect in vascular growth, including retinopathy of
      prematurity and persistent pulmonary hypertension of the newborn.

PMID- 21089715
TI  - Use of protein C concentrate in neonatal period.
AB  - Levels of protein C, low at birth, physiologically Increase until six months of
      age and achieve the adult range after puberty. Protein C deficiency may be
      congenital or acquired. Severe protein C deficiency is a rare autosomal recessive
      disorder that usually presents in neonatal period with purpura fulminans.
      Acquired protein C deficiency may be caused by increased consumption (e.g.,
      asphyxia, overt DIC, severe infection without overt DIC, acute VTE) or by
      decreased synthesis of the active carboxylated protein (e.g. administration of
      vitamin K antagonists, severe hepatic synthetic disfunction). Two different
      formulations of protein C are available: recombinant human activated protein C
      (rhAPC) and human plasma-derived viral-inactivated protein C. It is known that in
      septic patients replacement therapy with rhAPC reduces mortality but is
      associated with an increased risk of bleeding. During the neonatal period, when a
      higher risk of bleeding exists, the human plasma-derived viral-inactivated
      protein C concentrate may represent an effective therapeutic option. In fact, its
      administration results effective both in severe congenital and acquired forms of
      protein C deficiency.

PMID- 21089714
TI  - European registry of infants born to mothers with antiphospholipid syndrome:
      preliminary results.
AB  - The registry is an European, multicentre, prospective and longitudinal study
      which follows a cohort of children born to mothers with antiphospholipid syndrome
      (APS). In this article we report preliminary results obtained from 138 mothers
      and 141 babies (three twin pregnancies). At birth, 16.3% of neonates were less
      than 37 weeks of gestation and 17% were low birth weight; in addition, 11.3% of
      neonates were small for gestational age. No cases of neonatal thrombosis were
      observed. During follow-up period five children showed behavioral abnormalities.
      A long term clinical follow-up will be necessary to evaluate the
      neuropsychological development of these children.

PMID- 21089716
TI  - Alimentazione del neonato pretermine IUGR: studio multicentrico ADEPT (Abnormal
      Doppler Enteral Prescription Trial). (Feeding the IUGR premature newborn infant:
      the multicenter ADEPT study).
AB  - AIM: Pregnancies complicated by abnormal antenatal Doppler blood flow often
      result in the preterm delivery of a growth restricted baby. These babies have a
      high risk of milk intolerance and necrotising enterocolitis (1), and introduction
      of milk feeds is frequently delayed. Our aim was to determine the effect of early
      or late introduction on success of achieving full milk feeds and on adverse
      outcomes including NEC. METHODS: Eligible babies with birthweight below 10th
      centile and gestation below 34+6 weeks, born after abnormal antenatal Dopplers,
      were randomised between 20 and 48 hours to either early (24-48 hours) or late
      (120-144 hours) introduction of milk feeds. Babies with major congenital anomaly,
      in-utero transfusion, multi-organ failure or need for inotropes were excluded.
      Feed volumes and rate of increase were standardised, and were the same for both
      groups. Daily feed logs were kept. RESULTS: 404 babies were randomised from 56
      units in U.K. and Ireland (202 in each group). There were no important
      differences between groups at randomisation. CONCLUSION: growth restricted
      preterm infants born after absent or reversed end-diastolic flow in the umbilical
      artery who are fed from the second day after birth achieve full feeds faster than
      those commencing feeds on day six. No difference was been seen in the incidence
      of NEC, in preliminary analysis. Final data analysis is currently being completed
      and will be presented at the conference.

PMID- 21089717
TI  - Focus on pandemic 2009 H1N1 influenza (swine flu).
AB  - At the moment of the onset of the pandemic there were few data about the
      transmission of the 2009 H1N1 virus infection from the mother to the newborn.
      Nevertheless neonates born to an ill mother from 2 days before through 7 days
      after illness onset in the mother were thought to be exposed and potentially
      infected. In October 2009 the Infectious Disease Group of the Italian Society of
      Neonatology provided a guide regarded the management of suspected or confirmed
      maternal infection with 2009 H1N1 influenza virus within labor and delivery,
      postpartum, and newborn care settings in hospitals. It was based on the available
      scientific information, according to the U.S. Centers for Disease Control and
      Prevention (CDC) and the Italian Ministry of Labour, Health and Social Policy
      recommendations in order to protect the infant from exposure to respiratory
      secretion during or immediately after delivery. Moreover, we published 300,000
      copies of a more popular pamphlet for parents. Rigorous attention to Standard
      Precautions and Droplet Precautions is required to reduce the opportunities for
      the transmission of the infection in the health-care setting.

PMID- 21089718
TI  - Proteomics and neonatal infection.
AB  - Antimicrobial peptides plays an important role in the host innate defence
      network, even in humans. Recent studies demonstrated the capacity of human
      airways epithelial cells to synthesize antimicrobial peptides, and their
      multifunctional role in the primary immunity. The presence of ct-defensins in
      bronchoalveolar lavage fluid (BALF) was investigated in a cohort of preterm
      newborns with gestational age (GA) < or =30 weeks. BALF samples were analysed by
      High Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer.
      Our data show that preterm newborns, also at the lower GA, are able to produce
      defenses, underlining that their innate defence system is already active before
      the at-term delivery date.

PMID- 21089719
TI  - Neonatal bacterial meningitis.
AB  - Neonatal bacterial meningitis (NM) continues to be a serious disease with an
      unchanging rate of adverse outcome of 20-60%, despite a worldwide decline in
      mortality. The 3 major pathogens in developed countries are: Group B
      streptococcus, gram negative rods and Lysteria monocytogenes. Signs and symptoms
      of NM may be subtle, unspecific, vague, atypical or absent. In order to exclude
      NM, all infants with proven or suspected sepsis should undergo lumbar puncture.
      Positive culture of cerebrospinal fluid may be the only way to diagnose NM and to
      identify the pathogen, as CSF parameters Smay be normal at early stages and NM
      may occur frequently (up to 30% of cases) in the absence of bacteraemia. When NM
      is suspected, treatment must be aggressive, as the goal is to achieve
      bactericidal concentration of antibiotics and to sterilize CSF as soon as
      possible. Antibiotics should be administered intravenously, at the highest
      clinically validated doses. Empiric antibiotic treatment should include agents
      active against all main pathogens; currently the recommended empiric treatment of
      NM is ampicillin, plus an aminoglycoside and a third-generation cephalosporn.
      Therapy should be reassessed after cultures and antibiotic susceptibility is
      available. Prevention of neonatal sepsis, early recognition of infants at risk,
      prompt treatment and future adjunctive therapies will improve prognosis. Finally,
      we present the first preliminary Italian data on GBS meningitis. Data are
      obtained from an area-based study conducted In Emilia-Romagna during 2003 to
      2009.

PMID- 21089720
TI  - Neonatal pain and oxidative stress.
AB  - Neonatal analgesia is a recent issue: newborns were supposed to feel no pain
      until the late "80s; but from that date, many studies were performed to verify
      the extent of neonates" pain perception, ways to measure and overcome it. Pain
      can have harmful consequences in babies, due to several causes, and we
      investigated whether oxidative stress can play a role in this process. Here we
      resume our findings, that recall to a greater safeguard of babies from
      unjustified pain.

PMID- 21089721
TI  - Premedication for non-emergency intubation in the neonate.
AB  - Endotracheal intubation is frequently performed in neonatal intensive care. This
      procedure is extremely distressing and painful, and it has the potential for
      causing laryngospasm, hemodynamic changes, a rise in intracranial pressure and a
      risk of hemorrhage and airway injury. These adverse changes can be attenuated by
      using premedication with analgesic, sedative and muscle-relaxant drugs.
      Premedication is standard practice for pediatric and adult Intubation, but in
      neonates the use of supportive pharmacological measures is still hotly debated,
      mainly in terms of the risks and benefits of using sedatives in unstable and
      premature newborn. In a recent UK survey, 90% of tertiary neonatal units reported
      the routine use of sedation prior to intubation with a combination of atropine
      plus an opioid (morphine or fentanyl), while 82% of such units routinely use a
      muscle-relaxant. In Italy, a recent survey (in press) showed that the majority of
      NICU (Neonatal Intensive Care Units) use the sa me association of drugs for
      analgesia and sedation before tracheal intubation, but "not always" in more than
      half of these units. There is clearly a persistent concern about using such drugs
      in preterm and newborn infants, despite recent evidence showing that
      premedication for elective neonatal intubation is safer and more effective than
      when the infant is awake. Here we review the effects of using analgesic and
      sedative drugs on intubation conditions (good jaw relaxation, open and immobile
      vocal cord, suppression of pharyngeal and laryngeal reflex), on the time it takes
      to complete the procedure successfully, on pain control and the potentially
      adverse effects of using combinations of drugs for sedation.

PMID- 21089722
TI  - Aminoterminal B-type natriuretic peptide (NT-proBNP) in the therapy of patent
      ductus arteriosus.
AB  - BACKGROUND: NT-proBNP is a reliable index in case of cardiac diseases. OBJECTIVE:
      To evaluate the diagnostic usefulness of NT-proBNP as index of the closure of
      patent ductus arteriosus (PDA) in ELBW. METHODS: Considered 73 ELBW (mGA 26+3
      weeks; mBW 789 g) with echocardiographical diagnosis of PDA. The closure of the
      duct was spontaneous in 22%, pharmacological in 49.3% and by surgical ligation in
      28.7%. Plasma NT-proBNP levels were measured on day 3 in 35 preterm infants; in
      20 of them concentrations of the peptide were assayed on day 3 and on closure of
      the duct. RESULTS: On day 3 the median of NT-proBNP levels was 13718 pg/ml (range
      1918-70000). Peptide concentrations did not differ between pharmacological
      treatment and surgical ligation (respectively 13718 and 12342 pg/ml; p = 0.33).
      Concentrations of NT-proBNP were significantly lower on the closure of the duct
      (p < 0.0001) compared to concentrations on day 3 (median 12666 at day 3 versus
      2443.5 pg/ml at closure), with a decrease of 80.71%. CONCLUSIONS: ELBW showed
      high variability of NT-proBNP concentrations both on day 3 and on closure of PDA.
      Although NT-proBNP high levels were indicative of the presence of hsPDA, due to
      the extreme heterogeneity of the values it was not possible to determine an
      absolute cut-off concentration of NT-proBNP below which closure of the duct
      occurred, while a decrease of NT-proBNP > or =80% was a reliable index of PDA
      closure.

PMID- 21089723
TI  - Postnatal growth of preterm infants: which reference charts?
AB  - Preterm Infants' survival has greatly increased in the last few decades thanks to
      the improvement in obstetrical and neonatal care. These neonates constitute the
      large majority of the population in neonatal intensive care units. The correct
      evaluation of postnatal growth of these babies is nowadays of primary concern,
      although the definition of their optimal postnatal growth pattern is still
      controversial. Concerns have also been raised about the strategies to monitor
      their growth,specifically in relation to the charts used. At present the
      available charts in clinical practice are fetal growth charts, neonatal
      anthropometric charts and postnatal growth charts for term infants. None of
      these, for different reasons, is suitable to correctly evaluate preterm infant
      growth. An international multicentric project has recently started a study aiming
      at building a prescriptive standard for the evaluation of postnatal growth of
      preterm infants and it will be available in the next years. At present, while an
      international longitudinal standard for evaluating preterm infant postnatal
      growth is lacking, in Italy the best compromise in clinical practice is likely to
      be as follows: new Italian INeS (Italian Neonatal Study) charts up to term;
      International longitudinal charts WHO 2006 or CDC 2002 from term to two years;
      finally, the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP)
      2006 growth charts could be suitable for monitoring the growth of these infants
      from two years up to 20 years of age.

PMID- 21089724
TI  - Which is the ideal target for preterm growth?
AB  - In the last two decades the improved survival of very low birth weight (VLBW) and
      extremely low birth weight (ELBW) infants has underscored the problem of
      postnatal growth failure of these subjects. Notwithstanding the evident
      improvements in the general management of these infants during the hospital stay,
      most of them acquire a significant extrauterine growth restriction (EUGR).
      Frequent illnesses, medical and surgical therapies, feeding intolerance and, most
      of all, inadequacy of nutrient deliveries are responsible for the great part of
      this growth failure. However other factors, such as genetics, prenatal
      environment, hormones and metabolic pathways may contribute to growth impairment,
      that my persist until adulthood. Most of VLBW infants exhibit some catch-up
      growth, especially in late childhood and adolescence, but they generally remain
      smaller than their term peers. However, the most worrying aspect is related to
      the detrimental effect of growth impairment, especially if involving head
      circumference, on neurodevelopment outcomes of these infants. The endocrine,
      metabolic and cardiovascular long term consequences of under- and/or
      hypernutrition of VLBW infants are still to be elucidated. In the meantime, the
      efforts of the neonatotolgists should be focused on improving, how much as
      possible, the early nutrient management of these infants, allowing them to reach
      an adequate growth rate (at least 18-20 g/kg/d), then avoiding the need of a late
      unphysiological catch-up growth.

PMID- 21089725
TI  - Alimentazione del neonato pretermine alla dimissione. (Feeding of the premature
      newborn infant after discharge).

PMID- 21089726
TI  - L'outcome del neonato affetto da ernia diaframmatica congenita. (The outcome of
      the newborn infant suffering from congenital diaphragmatic hernia).
AB  - Congenital diaphragmatic hernia (CDH) is one of the most serious and
      controversial congenital anomalies. Pulmonary hypoplasia with/without pulmonary
      hypertension (and major associated anomalies) are reported the main causes of
      death in these patients. New treatment strategies for CDH have allowed an
      increase of survival also of more severe patients. As a consequence many
      attentions are now focused on long term follow up of these delicate babies. Many
      reports, in the last years, have highlighted associated morbidities in CDH
      survivors, such as pulmonary sequelae, neurodevelopmental delay, auxological
      deficits, gastrointestinal and orthopedic disorders. Therefore it is nowadays
      quite evident that this group of patient is a complex population to care during
      the first year of life but also throughout infancy and childhood, thus requiring
      a well defined follow up. Single institution data on overall survival have been
      frequently reported, only few of these however reported long term follow up of
      their patients. The aim of this short review is to describe the mid and long term
      outcomes of CDH survivors, suggesting also a personal view of follow up protocol
      for these babies.

PMID- 21089728
TI  - Clinical use of lactoferrin in preterm neonates: an update.
AB  - Sepsis-related morbidity and mortality is an increasing concern in all neonatal
      intensive care units, with reported incidences that are dramatically high
      regardless of the improvements in the quality of neonatal assistance.
      Antimicrobial resistance is also becoming a global and regional threat to public
      health. Neonatal sepsis include bloodstream, urine, cerebrospinal, peritoneal
      infections, and are classified as early-onset (occurring <3 days of life, EOS)
      and late-onset sepsis (LOS), i.e., infections arising after the perinatal period.
      Whereas prevention of EOS relies mainly on maternal-perinatal policies, attempts
      to reduce LOS incidence are a task merely for neonatologists but are hampered by
      non-specific clinical features, inadequate sensitivity of diagnostic tests, and
      late recognition. The frequent occurrence of late neurodevelopmental impairment
      after LOS challenges neonatologists to seek effective preventative strategies
      rather than more efficacious antibiotics for treatment. In the area of
      prevention, consistent evidence is accumulating on fluconazole--for prevention of
      fungal LOS--and, more recently, on bovine lactoferrin for prevention of both
      bacterial and fungal LOS: this innate immune system glycoprotein plays an
      important role in "in vivo" host defenses, and has been shown effective in a
      multicenter RCT recently published on VLBW neonates. Future studies are warranted
      to better elucidate the extent of the prevention provided by Ictoferrin and to
      identify the most suitable dosages to be administered.

PMID- 21089729
TI  - Too fast, too soon to call it "probiotic".
AB  - Probiotics (bacteria or yeasts) were defined by the Food Agricultural
      Organization (FAO) and the World Health Organization (WHO) joint report as live
      microorganisms which when administered in adequate amounts (in food or as a
      dietary supplement) confer a health benefit on the host. The best-demonstrated
      potential clinical benefits of probiotic agents, specifically in the pediatric
      population, are in the prevention and management of acute diarrhea, antibiotic
      associated diarrhea, and evidence is mounting on their potential benefits in
      atopic disease, inflammatory bowel conditions, and necrotizing enterocolitis.
      Their beneficial effects seem to be strain specific, thus, pooling data from
      different strains may result in misleading conclusions. Because there was no
      international consensus on methodology to assess efficiency and safety of
      probiotics, in 2001 the FAO/WHO undertook work to compile and evaluate the
      scientific evidence on functional and safety aspects of probiotics. International
      criteria have been developed to formulate unequivocal criteria for probiotic
      bacterial strains and products that contain them. More recently, the European
      Food Safety Authority (EFSA) highlighted as critical factors for probiotic health
      claim submissions genetic typing, internationally recognised naming protocols and
      evidence of consistency in the final product.

PMID- 21089730
TI  - Counselling in neonatal intensive care unit.
AB  - Counselling is a professional intervention based on skills to communicate and to
      build relationships. The project "Not alone", related to counselling at our
      Neonatal Intensive Care Unit, is aimed to let counselling become a "shared
      culture" for all the care givers. The first essential aspect is to form the
      ability of counselling through periodic courses for all professionals of the
      department (physicians, nurses, physiotherapists). In our department a
      professional counsellor is present assisting the medical staff in direct
      counselling. The counsellor's intervention allows a better parent orientation in
      the situation. A more effective sharing of these rules also facilitates the
      communication among parents and medical staff. Periodic meetings are established
      among the medical staff, in which the professional counsellor discusses difficult
      situations in order to share possible communicative strategies. We wanted to have
      not only a common communicative style, but also common subjects, independent from
      the characteristics of each of us. Individuals are often faced with diverse
      situations. For every setting that we more frequently face in communication (for
      example the first interview with a parent of a very preterm infant) we have built
      an "algorithm" that follows a pattern: (1) information always given; (2) frequent
      questions from parents, (3) frequent difficulties in the communication. We also
      need to record important moments, for instance the "case history of the
      communication": in fact it would be desirable to have the case history, a sheet
      dedicated to important communications that are absolutely to be shared with other
      professionals.

PMID- 21089731
TI  - Neonatal thrombosis.
AB  - Thrombosis is a special problem of the neonatal period, particularly in premature
      sick neonate, where it occurs with greater frequency than at other times of
      childhood. The aim of this article is to review the recommendations for the
      diagnosis and treatment of neonatal thrombosIs.

PMID- 21089732
TI  - Decision making in neonatologia.
AB  - The field of neonatology presents a fascinating context in which hugely important
      decisions have to be made on the basis of physicians' assessments of the long
      term consequences of various possible choices. In many cases such assessments
      cannot be derived from a consensual professional opinion; the situation is
      characterized by a high level of uncertainty. A sample of neonatologists in
      different countries received a questionnaire including vignette cases for which
      no clear consensus exists regarding the (probabilistic) prognosis. They were
      asked to (I) assess the probability of various outcomes (death, severe
      impairment) and (II) choose a treatment to be offered to the parents. Information
      on the physicians' professional and socio-demographic characteristics and their
      ethical "values" was also collected. The goal of this international survey is to
      understand the prognosis and to analyze decision making by professionals in the
      context of life and death in medicine. The availability of an identical
      technology in different social and institutional contexts should help identifying
      the convergences and differences under consideration. Seventy percent of those
      invited responded to the questionnaire (International 60-80%). Italian
      neonatologists seem to be quite pessimistic about the prognosis of infants at
      high risk of death or long term disabilities, they show a pro-life attitude, but
      in a certain proportion are willing to change their minds if requested by
      parents. Furthermore personal opinions predominate in the decision-making process
      and the contribution of team meeting and/or ethic consultation seem not
      significantly modify the decisions.

PMID- 21089733
TI  - From neonatal to paediatric intensive care: an educational pathway.
AB  - Neonatal and paediatric intensive care units (NICUs and PICUs) are growing in
      number, size and complexity, and each unit is staffed by a highly specialized
      group of doctors and nurses. Indeed, practitioners within these subspecialties
      acquire specific cognitive and procedural skills garnered from focused
      multidisciplinary training, as well as from experience with critically ill
      newborns and children. Although the NICUs and PICUs share many commonalities, the
      relationship between caregivers in the neonatal and paediatric critical care
      units often is characterized by rivalry and antagonism rather than by
      cooperation. In addition, as in the Italian scenario, the scientific and
      professional background in most cases differ between neonatologists,
      predominantly coming from a paediatric-oriented curriculum, and paediatric
      intensivists, mainly affiliated to adult anaesthesia and intensive care residency
      programs. However, in some circumstances, particularly when dealing with smaller
      patients, the limits between these two distinct disciplines appear quite vague,
      and undoubtedly many clinicians have the perception that the two branches, namely
      neonatology and paediatric anaesthesia and intensive care, would get a mutual
      benefit by a stronger collaboration and cross-contamination. Indeed, in some
      situations, such as shortage of PICU beds or patients not easily transferable to
      a PICU, neonatologists are occasionally called to take care of critically ill
      infants and young children. However, these "paediatric" patients may often
      present with complex pathologies which the neonatologist may not be familiar
      with. This condition raises important issues about the advisability to provide
      specific education and training in paediatric intensive care also to
      neonatologists, according to local needs and caregivers' expectations.

PMID- 21089734
TI  - Metabolomics: the "new clinical chemistry" for personalized neonatal medicine.
AB  - Metabolomics is a new approach based on the systematic study of the full
      complement of metabolites in a biological sample. This technology consists of two
      sequential steps: (1) an experimental technique, based on mass spectrometry or
      nuclear magnetic resonance (NMR) spectroscopy, designed to profile low molecular
      weight compounds, and (2) multivariate data analysis. Metabolomic analysis of
      biofluids or tissues has been successfully used in the fields of physiology,
      diagnostics, functional genomics, pharmacology, toxicology and nutrition. Recent
      studies have evaluated how physiological variables or pathological conditions can
      affect metabolomic profiles of different biofluids in pediatric populations.
      Little is known about the overall metabolic status of the term and preterm
      neonate. On the other hand, the management of sick or preterm newborns might be
      improved if more information on perinatal/neonatal maturational processes and
      their metabolic background were available. At present, the use of metabolomics in
      Neonatology is still in the pioneering phase. Meaningful diagnostic information
      and simple, non-invasive collection techniques make urine a particularly suitable
      biofluid for metabolomic approach in neonatal medicine. Using NMR-based
      metabolomic analysis of urine, distinct metabolic patterns have been shown to be
      associated with different classes of gestational age in a population of preterm
      and term infants. Together with genomics and proteomics, metabolomics appears to
      be a promising tool in Neonatology for the monitoring of postnatal metabolic
      maturation, the identification of biomarkers as early predictors of outcome, the
      diagnosis and monitoring of various diseases and the "tailored" management of
      neonatal disorders.

PMID- 21089735
TI  - Markers di stress ossidativo nei liquidi biologici. (Markers of oxidative stress
      in biological fluids).
AB  - The damaging effects of free radicals (FR) in the perinatal period may be
      detected by testing specific markers of oxidative stress (OS) in newborn's
      biological fluids. Currently, more than 70 different markers are used to assess
      both the damage caused by excessive production of FR and body's antioxidant
      response. Our goal is to identify reliable markers for the detection of OS in
      physiology and pathology. These biomarkers can be useful for several clinical
      purpose such as to monitor the response to any antioxidant intervention and then
      develop preventive strategies. The standardization and a large clinical use of
      these biomarkers should contribute to the daily neonatologists work in the early
      detection, management and therapy of the several neonatal FR diseases.

PMID- 21089736
TI  - Brain cooling therapy.
AB  - Therapeutic hypothermia (whole body or selective head cooling) is becoming
      standard of care for brain injury in infants with perinatal hypoxic ischemic
      encephalopathy (HIE). Brain cooling reduces the rate of apoptosis and early
      necrosis, reduces cerebral metabolic rate and the release of nitric oxide and
      free radicals. Animal models of perinatal brain injury show histological and
      functional improvement due to of early hypothermia. The brain protection depends
      on the temperature and time delay between insult and beginning of treatment (more
      effective with cooling to 33 +/- 0.5 degrees C, and less than 6 hours after
      hypoxic-ischemic insult). Recent meta-analyses and systematic reviews in human
      neonates show reduction in mortality and long-term neurodevelopmental disability
      at 12-24 months of age, with more favourable effects in the less severe forms of
      HIE. The authors describe their experience in 53 term newborns with moderate
      severe HIE treated with whole body cooling between 2001 and 2009, and studied
      with magnetic resonance imaging (MRI) and general movements (GMs) assessment. The
      creation of a network connecting the Neonatal Intensive Care Unit with the level
      I-II hospitals of the reference area, as part of regional network, is of
      paramount importance to enroll potential candidates and to start therapeutic
      hypothermia within optimal time window.

PMID- 21089737
TI  - Neonatal stroke.
AB  - The perinatal ischemic stroke is defined as "a group of heterogenous conditions
      with a focal disruption of cerebral flow secondary to an arterial or a venous
      thrombosis or embolization between the 20 week of foetal life through the 28 post
      natal day". Three subgroups are identified: arterial ischemic stroke (AIS),
      cerebral sinovenous thrombosis (CSVT) and haemorragic infarct. Many strokes are
      detected in the neonatal period due to early onset seizures, although symptoms
      can be more subtle leading to a significant delay in the diagnosis. MRI-DWI
      remains the best tool for a correct diagnosis, extension of the lesion and
      suggestion of timing. Lesions detected in utero or at early neonatal imaging with
      signs of tissue loss are considered "foetal stroke". The "neonatal stroke", with
      the symptoms in the first 4 days, shows the typical abnormalities of the acute
      phase evolving later in a white matter loss. The AIS shows the ischemic area of
      restriction at the early DWI in a arterial territory, mainly the middle cerebral
      artery. The MR-Venogram is useful in the CVST to detect the thrombus in a
      sinovenous vessel and the potentially associated lesion, such as intraventricular
      haemorrage and parenchymal oedema. The extension of the lesion and the
      involvement of the basal ganglia and thalami have a negative prognostic value for
      the development of hemiplegia especially in the presence of abnormal PLIC. An
      early diagnosis.

PMID- 21089738
TI  - The maturation of the central nervous system and the sensory systems in the NICU
      environment.

PMID- 21089739
TI  - Il neonato con sospetta sindrome genetica: esami di laboratoria e follow-up. (The
      newborn infant with a suspected genetic syndrome: laboratory tests and follow
      up).

PMID- 21089740
TI  - Laboratory investigations in genetic syndromes: examples of clinical approach in
      the neonatal unit.
AB  - Contiguous gene deletion syndromes: the importance of an accurate genetic
      definition for a careful clinical monitoring. Contiguous gene deletion syndromes
      are so named because the deletion manifests as a distinctive cluster of otherwise
      unrelated single-gene disorders in the same subject. An accurate genetic
      definition of the deleted region is extremely important for the appropriate
      management of these patients and for unravelling the function of the involved
      genes. The microarray-based comparative genomic hybridization (CGH arrays)
      analysis is the actual molecular method able to accurately define the bounds of a
      deleted region, since it allows an evaluation of DNA copy number alterations
      associated to chromosome abnormalities, with higher resolution than classical
      cytogenetics or chromosomal banding. The clinical presentation, the diagnostic
      course, the genetic investigations and the follow-up of a patient harbouring a
      contiguous gene deletion syndrome will be presented during the seminar. The
      newborn with ambiguous genitalia: diagnostic approach toward clinical and genetic
      definition. Disorders of sexual differentiation may depend on several different
      causes and pathogenetic mechanisms, which may interfere at different stages of
      the complex pathway of sexual determination and differentiation. Several genes
      are involved, together with hormones and receptors. The main disorders of sexual
      differentiation are characterized by dissociation between chromosomes and gonads
      or gonads and external genitalia appearance. Clinical phenotypes may be
      distinguished in true hermaphroditism and male or female pseudohermaphroditism.
      Diagnostic definition is based on clinical and instrumental evaluation and
      laboratory investigations (hormonal, cytogenetic and molecular genetic
      investigations). Early diagnosis may allow an appropriate medical and/or surgical
      treatment, involving a multidisciplinary equipe. The correct gender assessment
      must be guided by clinical and genetic diagnosis and, in the meantime, by the
      possibility of anatomic and functional recovery and the future reproductive
      opportunities.

PMID- 21089741
TI  - Genetic syndrome suspicion: examples of clinical approach in the neonatal unit.
AB  - Overgrowth syndromes: the practical clinical approach. Excessive growth can be
      present in a variety of medical conditions as result of abnormal fetal metabolism
      (i.e., maternal gestational diabetes) or of an overgrowth syndrome. Within this
      latter group of diseases, a LGA newborn requires a complex differential diagnosis
      encompassing several syndromes, such as Beckwith-Wiedemman, Sotos, Weaver,
      Simpson-Golabi-Behmel, Perlman, and Bannayan-Riley-Ruvalcaba. Partial or global
      overgrowth, other dysmorphisms, abdominal organs anomalies, as well as benign and
      malignant tumors are the common issues to examine for the diagnosis and the
      monitoring of all these disorders. The molecular bases of these conditions, even
      if partially known so far, can help in explaining the clinical features and
      prognosis. The diagnostic course, the genetic investigations and the follow-up of
      a LGA patient will be presented during the seminar. A wide clinical spectrum from
      esophageal atresia to VACTERL association. Oesophageal atresia (OA) occurs
      approximately in 1 in 3000 live births. It can be clinically divided into
      isolated and syndromic, when associated with other features. The aetiology is
      largely unknown and is likely to be multifactorial, however, various clues have
      been uncovered in animal experiments particularly defects in the expression of
      the gene Sonic hedgehog (Shh). The vast majority of cases are sporadic and the
      recurrence risk for siblings is 1%. Survival is directly related to birth weight
      and to the presence of a major cardiac defect. The VACTERL association refers to
      anomalies of the bony spinal column (V), atresias in the gastrointestinal tract
      (A), congenital heart lesions (C), tracheoesophageal defects (TE), renal and
      distal urinary tract anomalies (R) and limb lesions (L). The overall phenotype of
      a series of newborn patients we observed may vary widely, reflecting the
      aetiologic heterogeneity of this group of conditions. Therefore, possible
      additional defects must be accurately investigated in all newborns with OA.

PMID- 21089742
TI  - Fluid and electrolyte intake during the first week of life in preterm infants
      receiving parenteral nutrition according current guidelines.
AB  - There is growing evidence that early water and electrolyte homeostasis may be
      influenced by energy balance in preterm infants. Some fluid and electrolyte
      disturbances of postnatal life could be in part promoted by the catabolism due to
      withheld amino acid and energy supply after birth. According to current
      guidelines parenteral nutrition with relatively high protein and lipid needs is
      commenced on day one. By turning the nitrogen balance from negative to zero or
      even positive, amino acid administration could also minimize the occurrence of
      water and ions disturbances after birth especially in extremely preterm infants.
      Future researches are needed in order to further investigate the impact of amino
      acid and energy intake on early fluid balance in preterm infants.

PMID- 21089743
TI  - Enteral feeding: how, when, how much?
AB  - In a NICU early enteral feeding is usually possible only when the newborn
      clinical conditions permit it. Because of the frequent need of umbilical/central
      catheters, they usually start with parenteral feeding and/or with minimal enteral
      feeding (trophic feeding). This kind of management is even more frequent in
      VLBWIs, in which the risk of NEC is very high. In this work we describe a model
      of early enteral exclusive feeding (EEEF) based on the use of banking human milk
      followed by mother In the Centre of Neonatology of Trento, as in other milk.
      Centers, the newborns weighing less than 750 g or with a GE <27 weeks, are
      treated with parenteral nutrition and minimal enteral feeding. The newborn
      weighing 750-1249g and with GE >26 weeks define a group in which we find critical
      neonates, who can not be treated with enteral feeding, and neonates whose
      clinical conditions permit EEEF. In particular, in a period of 16 years (1994
      2009) in Trento, 308 newborns weighing 750-1249 g and GE >26 weeks were admitted.
      The 90.9% has been treated with prenatal steroids, the 91.9% was inborn, the
      96.1% survived. In the 59.1% of the cases (175) we gave EEEF. We could continue
      with a complete EEEF in the 40.2% of the total (119 cases). The characteristics
      of these neonates and our centre management, based mainly on early use of banking
      human milk and mother milk, are detailed described.

PMID- 21089744
TI  - Techniques of maternal milk extraction and storage for feeding VLBWI.

PMID- 21089745
TI  - Respiratory distress in newborn: evaluation of chest X-rays.
AB  - We discuss the anatomic and pathophysiological patterns of preterm and term
      newborn. Particular attention is directed to technical artefacts relating to the
      interpretation of chest radiography. We analyze the reading of chest X-Ray of
      preterm with low birth weight and poor lung maturation. Are also taken into
      account X-Ray features relating to alveolar "recruitment" and radiographic
      changes after surfactant's administration. We highlight the most important
      paintings of bruncopulmonary dysplasia and its evolution. The most frequent
      neonatal pulmonary inflammation and thoraco-pulmonary malformation, that may
      affect more the neonatologist, are mentioned. We discuss the new diagnostic
      approach with non invasive techniques (ultrasound) in the neonatal distress. Some
      easily recognizable congenital heart disease are finally describes.

PMID- 21089747
TI  - Acute peritoneal dialysis in neonatal intensive care units.

PMID- 21089748
TI  - Point/counterpoint. Medical physics should adopt double-blind peer review of all
      manuscripts.

PMID- 21089749
TI  - Metal artifact suppression from reformatted projections in multislice helical CT
      using dual-front active contours.
AB  - PURPOSE: Large metallic implants, such as hip prosthesis and shoulder implants,
      can cause severe artifacts in CT exams. As such, there have been significant
      efforts on the design of various image- or projection-based correction methods or
      iterative reconstruction methods with the hope to reconstruct artifact-free
      images. Unfortunately, suppression of metal artifacts remains a very challenging
      problem, in which metal region segmentation is one of the most important steps in
      assuring the efficiency of artifact suppression. In this article, the authors
      propose a novel, semiautomatic metal region segmentation algorithm based on a
      dual-front active contour model and a boundary mapping strategy to detect
      multiple large metal implants on reformatted projection data and to effectively
      suppress or eliminate metal artifacts on reconstructed images. METHODS: First,
      the projections created from helical scan data were reformatted by combining data
      at the same view angle over the full longitudinal scan range. In this way, the
      shape, location, and number of the metal structures show up clearly on each
      reformatted projection, changing only slightly between adjacent projections.
      Second, an initial boundary on one of the reformatted projections is defined, and
      a boundary mapping strategy was utilized to map the metal boundary on the first
      reformatted projection to the next adjacent projection. Third, a novel dual-front
      active contour model was used to evolve the mapped boundary from the prior
      projection to the actual boundary in the current projection. By iteratively
      performing the boundary mapping and boundary evolution procedure, the metal
      structures (one or multiple) on all the projections can be extracted efficiently
      and accurately. Finally, a Delaunay triangulation was applied to fill the metal
      shadows and the corrected projection data were reconstructed with a commercially
      available algorithm. RESULTS: Experimental studies on clinical hip and shoulder
      CT exams and a comparison with a gradient-based threshold method were performed.
      The results demonstrated that the proposed segmentation strategy was able to
      segment multiple metal implants more accurately than the threshold method. Soft
      tissue visibility was improved dramatically. CONCLUSIONS: In total, the artifacts
      caused by dense metal implants were suppressed dramatically with the proposed
      metal artifact suppression technique.

PMID- 21089750
TI  - Differentiation between diamagnetic and paramagnetic cerebral lesions based on
      magnetic susceptibility mapping.
AB  - PURPOSE: Identification of calcifications and hemorrhages is essential for the
      etiological diagnosis of cerebral lesions. The purpose of this work was to
      develop a robust method for characterization of para- and diamagnetic
      intracerebral lesions based on clinical gradient-echo magnetic resonance phase
      data acquired at 1.5 Tesla. METHODS: The magnetic susceptibility distribution of
      biological tissue produces a distinct magnetic field pattern, which is directly
      reflected in gradient-echo magnetic resonance phase images. Compared to brain
      parenchyma, iron-laden tissues are more paramagnetic, whereas mineralized tissues
      usually possess more diamagnetic susceptibilities. Magnetic resonance phase data
      were inverted to the underlying susceptibility distribution utilizing additional
      geometrical information about the lesions, which was obtained from the gradient
      echo magnitude signal void corresponding to the lesions. Clinical magnetic
      resonance exams of three patients with multiple brain lesions (total n = 70) were
      processed and evaluated. For one patient, the results were validated by an
      additionally available computed tomography scan. Numerical simulations were
      conducted to evaluate the robustness of the method. RESULTS: The obtained
      susceptibility maps showed impressive delineation of lesions, vessels, and
      potentially iron-laden tissue. Compensation of the nonlocal field perturbations
      was clearly discernable on the susceptibility maps. In all cases, discrimination
      of para- from diamagnetic lesions was achieved and the results were confirmed by
      the additional computed tomography. The numerical simulations demonstrated that
      robust determination of the total magnetic moment of lesions is possible. Thus,
      the proposed method is able to yield quantitative values for the minimum magnetic
      susceptibility of lesions. CONCLUSIONS: A method has been developed for
      noninvasive, semiautomatic characterization of brain lesions based on magnetic
      resonance imaging data. Initial clinical results demonstrated that the proposed
      technique can be applied to diagnosis of lesions with calcifications or
      hemorrhages. If confirmed by larger studies, it bears the potential to obviate
      the need for confirmation with computed tomography.

PMID- 21089751
TI  - Empirical beam hardening correction (EBHC) for CT.
AB  - PURPOSE: Due to x-ray beam polychromaticity and scattered radiation, attenuation
      measurements tend to be underestimated. Cupping and beam hardening artifacts
      become apparent in the reconstructed CT images. If only one material such as
      water, for example, is present, these artifacts can be reduced by precorrecting
      the rawdata. Higher order beam hardening artifacts, as they result when a mixture
      of materials such as water and bone, or water and bone and iodine is present,
      require an iterative beam hardening correction where the image is segmented into
      different materials and those are forward projected to obtain new rawdata.
      Typically, the forward projection must correctly model the beam polychromaticity
      and account for all physical effects, including the energy dependence of the
      assumed materials in the patient, the detector response, and others. We propose a
      new algorithm that does not require any knowledge about spectra or attenuation
      coefficients and that does not need to be calibrated. The proposed method
      corrects beam hardening in single energy CT data. METHODS: The only a priori
      knowledge entering EBHC is the segmentation of the object into different
      materials. Materials other than water are segmented from the original image,
      e.g., by using simple thresholding. Then, a (monochromatic) forward projection of
      these other materials is performed. The measured rawdata and the forward
      projected material-specific rawdata are monomially combined (e.g., multiplied or
      squared) and reconstructed to yield a set of correction volumes. These are then
      linearly combined and added to the original volume. The combination weights are
      determined to maximize the flatness of the new and corrected volume. EBHC is
      evaluated using data acquired with a modern cone-beam dual-source spiral CT
      scanner (Somatom Definition Flash, Siemens Healthcare, Forchheim, Germany), with
      a modern dual-source micro-CT scanner (Tomo-Scope Synergy Twin, CT Imaging GmbH,
      Erlangen, Germany), and with a modern C-arm CT scanner (Axiom Artis dTA, Siemens
      Healthcare, Forchheim, Germany). A large variety of phantom, small animal, and
      patient data were used to demonstrate the data and system independence of EBHC.
      RESULTS: Although no physics apart from the initial segmentation procedure enter
      the correction process, beam hardening artifacts were significantly reduced by
      EBHC. The image quality for clinical CT, micro-CT, and C-arm CT was highly
      improved. Only in the case of C-arm CT, where high scatter levels and calibration
      errors occur, the relative improvement was smaller. CONCLUSIONS: The empirical
      beam hardening correction is an interesting alternative to conventional iterative
      higher order beam hardening correction algorithms. It does not tend to over- or
      undercorrect the data. Apart from the segmentation step, EBHC does not require
      assumptions on the spectra or on the type of material involved. Potentially, it
      can therefore be applied to any CT image.

PMID- 21089752
TI  - Sensitivity of low energy brachytherapy Monte Carlo dose calculations to
      uncertainties in human tissue composition.
AB  - PURPOSE: The objective of this work is to assess the sensitivity of Monte Carlo
      (MC) dose calculations to uncertainties in human tissue composition for a range
      of low photon energy brachytherapy sources: 125I, 103Pd, 131Cs, and an electronic
      brachytherapy source (EBS). The low energy photons emitted by these sources make
      the dosimetry sensitive to variations in tissue atomic number due to the
      dominance of the photoelectric effect. This work reports dose to a small mass of
      water in medium D(w,m) as opposed to dose to a small mass of medium in medium
      D(m,m). METHODS: Mean adipose, mammary gland, and breast tissues (as uniform
      mixture of the aforementioned tissues) are investigated as well as compositions
      corresponding to one standard deviation from the mean. Prostate mean compositions
      from three different literature sources are also investigated. Three sets of MC
      simulations are performed with the GEANT4 code: (1) Dose calculations for
      idealized TG-43-like spherical geometries using point sources. Radial dose
      profiles obtained in different media are compared to assess the influence of
      compositional uncertainties. (2) Dose calculations for four clinical prostate LDR
      brachytherapy permanent seed implants using 125I seeds (Model 2301, Best Medical,
      Springfield, VA). The effect of varying the prostate composition in the planning
      target volume (PTV) is investigated by comparing PTV D90 values. (3) Dose
      calculations for four clinical breast LDR brachytherapy permanent seed implants
      using 103Pd seeds (Model 2335, Best Medical). The effects of varying the
      adipose/gland ratio in the PTV and of varying the elemental composition of
      adipose and gland within one standard deviation of the assumed mean composition
      are investigated by comparing PTV D90 values. For (2) and (3), the influence of
      using the mass density from CT scans instead of unit mass density is also
      assessed. RESULTS: Results from simulation (1) show that variations in the mean
      compositions of tissues affect low energy brachytherapy dosimetry. Dose
      differences between mean and one standard deviation of the mean composition
      increasing with distance from the source are observed. It is established that the
      125I and 131Cs sources are the least sensitive to variations in elemental
      compositions while 103Pd is most sensitive. The EBS falls in between and exhibits
      complex behavior due to significant spectral hardening. Results from simulation
      (2) show that two prostate compositions are dosimetrically equivalent to water
      while the third shows D90 differences of up to 4%. Results from simulation (3)
      show that breast is more sensitive than prostate with dose variations of up to
      30% from water for 70% adipose/30% gland breast. The variability of the breast
      composition adds a +/- 10% dose variation. CONCLUSIONS: Low energy brachytherapy
      dose distributions in tissue differ from water and are influenced by density,
      mean tissue composition, and patient-to-patient composition variations. The
      results support the use of a dose calculation algorithm accounting for
      heterogeneities such as MC. Since this work shows that variations in mean tissue
      compositions affect MC dosimetry and result in increased dose uncertainties, the
      authors conclude that imaging tools providing more accurate estimates of
      elemental compositions such as dual energy CT would be beneficial.

PMID- 21089753
TI  - Fundus image fusion in EYEPLAN software: an evaluation of a novel technique for
      ocular melanoma radiation treatment planning.
AB  - PURPOSE: The purpose of this study is to evaluate a novel approach for treatment
      planning using digital fundus image fusion in EYEPLAN for proton beam radiation
      therapy (PBRT) planning for ocular melanoma. The authors used a prototype version
      of EYEPLAN software, which allows for digital registration of high-resolution
      fundus photographs. The authors examined the improvement in tumor localization by
      replanning with the addition of fundus photo superimposition in patients with
      macular area tumors. METHODS: The new version of EYEPLAN (v3.05) software allows
      for the registration of fundus photographs as a background image. This is then
      used in conjunction with clinical examination, tantalum marker clips, surgeon's
      mapping, and ultrasound to draw the tumor contour accurately. In order to
      determine if the fundus image superimposition helps in tumor delineation and
      treatment planning, the authors identified 79 patients with choroidal melanoma in
      the macular location that were treated with PBRT. All patients were treated to a
      dose of 56 GyE in four fractions. The authors reviewed and replanned all 79
      macular melanoma cases with superimposition of pretreatment and post-treatment
      fundus imaging in the new EYEPLAN software. For patients with no local failure,
      the authors analyzed whether fundus photograph fusion accurately depicted and
      confirmed tumor volumes as outlined in the original treatment plan. For patients
      with local failure, the authors determined whether the addition of the fundus
      photograph might have benefited in terms of more accurate tumor volume
      delineation. RESULTS: The mean follow-up of patients was 33.6 +/- 23 months.
      Tumor growth was seen in six eyes of the 79 macular lesions. All six patients
      were marginal failures or tumor miss in the region of dose fall-off, including
      one patient with both in-field recurrence as well as marginal. Among the six
      recurrences, three were managed by enucleation and one underwent retreatment with
      proton therapy. Three patients developed distant metastasis and all three
      patients have since died. The replanning of six patients with their original
      fundus photograph superimposed showed that in four cases, the treatment field
      adequately covered the tumor volume. In the other two patients, the overlaid
      fundus photographs indicated the area of marginal miss. The replanning with the
      fundus photograph showed improved tumor coverage in these two macular lesions.
      For the remaining patients without local failure, replanning with fundus
      photograph superimposition confirmed the tumor volume as drawn in the original
      treatment plan. CONCLUSIONS: Local control was excellent in patients receiving 56
      GyE of PBRT for uveal melanomas in the macular region, which traditionally can be
      more difficult to control. Posterior lesions are better defined with the
      additional use of fundus image since they can be difficult to mark surgically. In
      one-third of treatment failing patients, the superposition of the fundus
      photograph would have clearly allowed improved localization of tumor. The current
      practice standard is to use the superimposition of the fundus photograph in
      addition to the surgeon's clinical and clip mapping of the tumor and ultrasound
      measurement to draw the tumor volume.

PMID- 21089754
TI  - Monte Carlo characterization of skin doses in 6 MV transverse field MRI-linac
      systems: effect of field size, surface orientation, magnetic field strength, and
      exit bolus.
AB  - PURPOSE: The main focus of this work is to continue investigations into the Monte
      Carlo predicted skin doses seen in MRI-guided radiotherapy. In particular, the
      authors aim to characterize the 70 microm skin doses over a larger range of
      magnetic field strength and x-ray field size than in the current literature. The
      effect of surface orientation on both the entry and exit sides is also studied.
      Finally, the use of exit bolus is also investigated for minimizing the negative
      effects of the electron return effect (ERE) on the exit skin dose. METHODS: High
      resolution GEANT4 Monte Carlo simulations of a water phantom exposed to a 6 MV x
      ray beam (Varian 2100C) have been performed. Transverse magnetic fields of
      strengths between 0 and 3 T have been applied to a 30 x 30 x 20 cm3 phantom. This
      phantom is also altered to have variable entry and exit surfaces with respect to
      the beam central axis and they range from -75 degrees to +75 degrees. The exit
      bolus simulated is a 1 cm thick (water equivalent) slab located on the beam exit
      side. RESULTS: On the entry side, significant skin doses at the beam central axis
      are reported for large positive surface angles and strong magnetic fields.
      However, over the entry surface angle range of -30 degrees to -60 degrees, the
      entry skin dose is comparable to or less than the zero magnetic field skin dose,
      regardless of magnetic field strength and field size. On the exit side, moderate
      to high central axis skin dose increases are expected except at large positive
      surface angles. For exit bolus of 1 cm thickness, the central axis exit skin dose
      becomes an almost consistent value regardless of magnetic field strength or exit
      surface angle. This is due to the almost complete absorption of the ERE electrons
      by the bolus. CONCLUSIONS: There is an ideal entry angle range of -30 degrees to 
      60 degrees where entry skin dose is comparable to or less than the zero magnetic
      field skin dose. Other than this, the entry skin dose increases are significant,
      especially at higher magnetic fields. On the exit side there is mostly moderate
      to high skin dose increases for 0.2-3 T with the only exception being large
      positive angles. Exit bolus of 1 cm thickness will have a significant impact on
      lowering such exit skin dose increases that occur as a result of the ERE.

PMID- 21089755
TI  - VMC++ validation for photon beams in the energy range of 20-1000 keV.
AB  - PURPOSE: In high energy teletherapy, VMC++ is known to be a very accurate and
      efficient Monte Carlo (MC) code. In principle, the MC method is also a powerful
      dose calculation tool in other areas in radiation oncology, e.g., brachytherapy
      or orthovoltage radiotherapy. However, VMC++ is not validated for the low-energy
      range of such applications. This work aims in the validation of the VMC++ MC code
      for photon beams in the energy range between 20 and 1000 keV. METHODS: Dose
      calculations were performed in different 40 x 40 x 40 cm3 phantoms of different
      materials. Dose distributions of monoenergetic (ranging from 20 to 1000 keV) 10 x
      10 and 2 x 2 cm2 parallel beams were calculated. Voxel sizes of 4 x 4 x 4 and 1 x
      1 x 1 mm3 were used for the dose calculations. The resulting dose distributions
      were compared to those calculated using EGSnrc, which is used as a golden
      standard in this work. RESULTS: At energies between 100 and 1000 keV, EGSnrc and
      VMC++ calculated dose distributions agree within the statistical uncertainty of
      about 1% (1sigma). At energies < or = 50 keV, dose differences of up to 1.6% (in
      % of D(max)) occur when VMC++ and EGSnrc are compared. Turning off Rayleigh
      scattering, binding effects for Compton scattering, and the atomic relaxation
      after photoelectric absorption in EGSnrc (all not implemented in VMC++) leads to
      an agreement between both MC codes within statistical uncertainty. Further, using
      the KERMA approximation feature implemented in VMC++ leads to very efficient
      simulations in the energy range between 20 and 1000 keV. CONCLUSIONS: Further
      improvements for very low energies in accuracy of VMC++ could be achieved by
      implementing Rayleigh scattering, binding effects for Compton scattering, and the
      atomic relaxation after photoelectric absorption. Implementation into VMC++ of
      KERMA approximation has been validated.

PMID- 21089756
TI  - Monte Carlo simulation of the effect of miniphantom on in-air output ratio.
AB  - PURPOSE: The aim of the study was to quantify the effect of miniphantoms on in
      air output ratio measurements, i.e., to determine correction factors for in-air
      output ratio. METHODS: Monte Carlo (MC) simulations were performed to simulate in
      air output ratio measurements by using miniphantoms made of various materials
      (PMMA, graphite, copper, brass, and lead) and with different longitudinal
      thicknesses or depths (2-30 g/cm2) in photon beams of 6 and 15 MV, respectively,
      and with collimator settings ranging from 3 x 3 to 40 x 40 cm2. EGSnrc and
      BEAMnrc (2007) software packages were used. Photon energy spectra corresponding
      to the collimator settings were obtained from BEAMnrc code simulations on a
      linear accelerator and were used to quantify the components of in-air output
      ratio correction factors, i.e., attenuation, mass energy absorption, and phantom
      scatter correction factors. In-air output ratio correction factors as functions
      of miniphantom material, miniphantom longitudinal thickness, and collimator
      setting were calculated and compared to a previous experimental study. RESULTS:
      The in-air output ratio correction factors increase with collimator opening and
      miniphantom longitudinal thickness for all the materials and for both energies.
      At small longitudinal thicknesses, the in-air output ratio correction factors for
      PMMA and graphite are close to 1. The maximum magnitudes of the in-air output
      ratio correction factors occur at the largest collimator setting (40 x 40 cm2)
      and the largest miniphantom longitudinal thickness (30 g/cm2): 1.008 +/- 0.001
      for 6 MV and 1.012 +/- 0.001 for 15 MV, respectively. The MC simulations of the
      in-air output ratio correction factor confirm the previous experimental study.
      CONCLUSIONS: The study has verified that a correction factor for in-air output
      ratio can be obtained as a product of attenuation correction factor, mass energy
      absorption correction factor, and phantom scatter correction factor. The
      correction factors obtained in the present study can be used in studies involving
      in-air output ratio measurements using miniphantoms.

PMID- 21089757
TI  - Higher-order phase shift reconstruction approach.
AB  - PURPOSE: Biological soft tissues encountered in clinical and preclinical imaging
      mainly consists of atoms of light elements with low atomic numbers and their
      elemental composition is nearly uniform with little density variation. Hence, x
      ray attenuation contrast is relatively poor and cannot achieve satisfactory
      sensitivity and specificity. In contrast, x-ray phase-contrast provides a new
      mechanism for soft tissue imaging. The x-ray phase shift of soft tissues is about
      a thousand times greater than the x-ray absorption over the diagnostic x-ray
      energy range, yielding a higher signal-to-noise ratio than the attenuation
      contrast counterpart. Thus, phase-contrast imaging is a promising technique to
      reveal detailed structural variation in soft tissues, offering a high contrast
      resolution between healthy and malignant tissues. Here the authors develop a
      novel phase retrieval method to reconstruct the phase image on the object plane
      from the intensity measurements. The reconstructed phase image is a projection of
      the phase shift induced by an object and serves as input to reconstruct the 3D
      refractive index distribution inside the object using a tomographic
      reconstruction algorithm. Such x-ray refractive index images can reveal
      structural features in soft tissues, with excellent resolution differentiating
      healthy and malignant tissues. METHODS: A novel phase retrieval approach is
      proposed to reconstruct an x-ray phase image of an object based on the paraxial
      Fresnel-Kirchhoff diffraction theory. A primary advantage of the authors'
      approach is higher-order accuracy over that with the conventional linear
      approximation models, relaxing the current restriction of slow phase variation.
      The nonlinear terms in the autocorrelation equation of the Fresnel diffraction
      pattern are eliminated using intensity images measured at different distances in
      the Fresnel diffraction region, simplifying the phase reconstruction to a linear
      inverse problem. Numerical experiments are performed to demonstrate the accuracy
      and stability of the proposed approach. RESULTS: The proposed reconstruction
      formula is a generalization of the transport of intensity equation (TIE). It has
      the second-order accuracy compared to the linear model used in the conventional
      phase retrieval approach. The numerical experiments demonstrate that the accuracy
      and stability of the proposed phase reconstruction method outperforms the TIE
      based reconstruction method. CONCLUSIONS: A novel approach has been proposed to
      retrieve an x-ray phase shift image induced by an object from intensity images
      measured at different distances in the Fresnel diffraction region. The authors'
      approach has the second-order accuracy and is able to retrieve the phase shift of
      an object stably, overcoming the restriction of slow phase variation assumed by
      the conventional phase retrieval techniques.

PMID- 21089758
TI  - Cascaded analysis of signal and noise propagation through a heterogeneous breast
      model.
AB  - PURPOSE: The detectability of lesions in radiographic images can be impaired by
      patterns caused by the surrounding anatomic structures. The presence of such
      patterns is often referred to as anatomic noise. Others have previously extended
      signal and noise propagation theory to include variable background structure as
      an additional noise term and used in simulations for analysis by human and ideal
      observers. Here, the analytic forms of the signal and noise transfer are derived
      to obtain an exact expression for any input random distribution and the "power
      law" filter used to generate the texture of the tissue distribution. METHODS: A
      cascaded analysis of propagation through a heterogeneous model is derived for x
      ray projection through simulated heterogeneous backgrounds. This is achieved by
      considering transmission through the breast as a correlated amplification point
      process. The analytic forms of the cascaded analysis were compared to
      monoenergetic Monte Carlo simulations of x-ray propagation through power law
      structured backgrounds. RESULTS: As expected, it was found that although the
      quantum noise power component scales linearly with the x-ray signal, the anatomic
      noise will scale with the square of the x-ray signal. There was a good agreement
      between results obtained using analytic expressions for the noise power and those
      from Monte Carlo simulations for different background textures, random input
      functions, and x-ray fluence. CONCLUSIONS: Analytic equations for the signal and
      noise properties of heterogeneous backgrounds were derived. These may be used in
      direct analysis or as a tool to validate simulations in evaluating detectability.

PMID- 21089759
TI  - Dose modeling in ultraviolet phototherapy.
AB  - PURPOSE: Ultraviolet phototherapy is widely used in the treatment of numerous
      skin conditions. This treatment is well established and largely beneficial to
      patients on both physical and psychological levels; however, overexposure to
      ultraviolet radiation (UVR) can have detrimental effects, such as erythemal
      responses and ocular damage in addition to the potentially carcinogenic nature of
      UVR. For these reasons, it is essential to control and quantify the radiation
      dose incident upon the patient to ensure that it is both biologically effective
      and has the minimal possible impact on the surrounding unaffected tissue.
      METHODS: To date, there has been little work on dose modeling, and the output of
      artificial UVR sources is an area where research has been recommended. This work
      characterizes these sources by formalizing an approach from first principles and
      experimentally examining this model. RESULTS: An implementation of a line source
      model is found to give impressive accuracy and quantifies the output radiation
      well. CONCLUSIONS: This method could potentially serve as a basis for a full
      computational dose model for quantifying patient dose.

PMID- 21089760
TI  - Dose optimization in pediatric cardiac x-ray imaging.
AB  - PURPOSE: The aim of this research was to explore x-ray beam parameters with
      intent to optimize pediatric x-ray settings in the cardiac catheterization
      laboratory. This study examined the effects of peak x-ray tube voltage (kVp) and
      of copper (Cu) x-ray beam filtration independently on the image quality to dose
      balance for pediatric patient sizes. The impact of antiscatter grid removal on
      the image quality to dose balance was also investigated. METHODS: Image sequences
      of polymethyl methacrylate phantoms approximating chest sizes typical of
      pediatric patients were captured using a modern flat-panel receptor based x-ray
      imaging system. Tin was used to simulate iodine-based contrast medium used in
      clinical procedures. Measurements of tin detail contrast and flat field image
      noise provided the contrast to noise ratio. Entrance surface dose (ESD) and
      effective dose (E) measurements were obtained to calculate the figure of merit
      (FOM), CNR2/dose, which evaluated the dose efficiency of the x-ray parameters
      investigated. The kVp, tube current (mA), and pulse duration were set manually by
      overriding the system's automatic dose control mechanisms. Images were captured
      with 0, 0.1, 0.25, 0.4, and 0.9 mm added Cu filtration, for 50, 55, 60, 65, and
      70 kVp with the antiscatter grid in place, and then with it removed. RESULTS: For
      a given phantom thickness, as the Cu filter thickness was increased, lower kVp
      was favored. Examining kVp alone, lower values were generally favored, more so
      for thinner phantoms. Considering ESD, the 8.5 cm phantom had the highest FOM at
      50 kVp using 0.4 mm of Cu filtration. The 12 cm phantom had the highest FOM at 55
      kVp using 0.9 mm Cu, and the 16 cm phantom had highest FOM at 55 kVp using 0.4 mm
      Cu. With regard to E, the 8.5 and 12 cm phantoms had the highest FOM at 50 kVp
      using 0.4 mm of Cu filtration, and the 16 cm phantom had the highest FOM at 50
      kVp using 0.25 mm Cu. Antiscatter grid removal improved the FOM for a given set
      of x-ray conditions. Under aforesaid optimal settings, the 8.5 cm phantom FOM
      improved by 24% and 33% for ESD and E, respectively. Corresponding improvements
      were 26% and 24% for the 12 cm phantom and 6% and 15% for the 16 cm phantom.
      CONCLUSIONS: For pediatric patients, using 0.25-0.9 mm Cu filtration in the x-ray
      beam while maintaining 50-55 kVp, depending on patient size, provided optimal x
      ray image quality to dose ratios. These settings, adjusted for x-ray tube loading
      limits and clinically acceptable image quality, should provide a useful strategy
      for optimizing iodine contrast agent based cardiac x-ray imaging. Removing the
      antiscatter grid improved the FOM for the 8.5 and 12 cm phantoms, therefore grid
      removal is recommended for younger children. Improvement for the 16 cm phantom
      declined into the estimated margin of error for the FOM; the need for grid
      removal for older children would depend on practical feasibility in the clinical
      environment.

PMID- 21089761
TI  - Modeling scatter-to-primary dose ratio for megavoltage photon beams.
AB  - PURPOSE: A three-parameter semiempirical model for scatter-to-primary dose ratio
      (SPR) is proposed to fit PDD (or TPR) and S(p) beam data. The SPR formula
      proposed in this study is more accurate than the previously published formula
      utilizing two parameters, especially for lower energy megavoltage photon beams,
      because the effect of backscattered photons is now taken into account. METHODS:
      Monte Carlo (MC) calculated SPR for photon energy spectrum between 60Co and 24 MV
      are used to evaluate the accuracy of the models. Based on fitting the MC data,
      the dependence of the SPR parameters (a0, w0,d0) with the attenuation
      coefficients of the photon beams is obtained and they were incorporated into the
      authors' optimization routine. The ability of the optimization routine to fit
      measured clinic data is examined for photon energies ranging from 60Co to 25 MV
      for all major cobalt and linear accelerator manufacturers. RESULTS: The authors'
      model successfully fits the measured photon beam data for field size (E/3-40 cm),
      where E is photon energy in MV and for clinically usable depths, d(max) to 20 cm
      for 60Co, d(max) to 30 cm for 4 MV, and d(max) to 40 cm for 6 MV and higher
      photon energies. The maximum error among these fits is better than 2% for photon
      energies above 60Co. CONCLUSIONS: The new SPR formula, along with the
      optimization routine, can serve as an efficient tool for performing quality
      control of x-ray beam data that conforms to AAPM Radiation Therapy Committee TG40
      and Therapy Physics Committee TG142 reports on beam data requirement.

PMID- 21089762
TI  - Monte Carlo study of the energy and angular dependence of the response of plastic
      scintillation detectors in photon beams.
AB  - PURPOSE: By using Monte Carlo simulations, the authors investigated the energy
      and angular dependence of the response of plastic scintillation detectors (PSDs)
      in photon beams. METHODS: Three PSDs were modeled in this study: A plastic
      scintillator (BC-400) and a scintillating fiber (BCF-12), both attached by a
      plastic-core optical fiber stem, and a plastic scintillator (BC-400) attached by
      an air-core optical fiber stem with a silica tube coated with silver. The authors
      then calculated, with low statistical uncertainty, the energy and angular
      dependences of the PSDs' responses in a water phantom. For energy dependence, the
      response of the detectors is calculated as the detector dose per unit water dose.
      The perturbation caused by the optical fiber stem connected to the PSD to guide
      the optical light to a photodetector was studied in simulations using different
      optical fiber materials. RESULTS: For the energy dependence of the PSDs in photon
      beams, the PSDs with plastic-core fiber have excellent energy independence within
      about 0.5% at photon energies ranging from 300 keV (monoenergetic) to 18 MV
      (linac beam). The PSD with an air-core optical fiber with a silica tube also has
      good energy independence within 1% in the same photon energy range. For the
      angular dependence, the relative response of all the three modeled PSDs is within
      2% for all the angles in a 6 MV photon beam. This is also true in a 300 keV
      monoenergetic photon beam for PSDs with plastic-core fiber. For the PSD with an
      air-core fiber with a silica tube in the 300 keV beam, the relative response
      varies within 1% for most of the angles, except in the case when the fiber stem
      is pointing right to the radiation source in which case the PSD may over-response
      by more than 10%. CONCLUSIONS: At +/- 1% level, no beam energy correction is
      necessary for the response of all three PSDs modeled in this study in the photon
      energy ranges from 200 keV (monoenergetic) to 18 MV (linac beam). The PSD would
      be even closer to water equivalent if there is a silica tube around the sensitive
      volume. The angular dependence of the response of the three PSDs in a 6 MV photon
      beam is not of concern at 2% level.

PMID- 21089764
TI  - Evaluation of spherical fiducial localization in C-arm cone-beam CT using patient
      data.
AB  - PURPOSE: C-arm based cone-beam CT (CBCT) has been recently introduced as an in
      situ 3D soft tissue imaging modality. When combined with image-guided navigation,
      it provides a streamlined clinical workflow with, potentially, improved
      interventional accuracy. A key component in these systems is image to patient
      registration. The most common registration method relies on fiducial markers
      placed on the patient's skin. The fiducials are localized in the volumetric image
      and in the interventional environment. When using C-arm CBCT, the small spatial
      extent of the volumetric reconstruction makes this registration approach
      challenging, as the volume must include both the anatomy of interest and the
      fiducials. The authors have previously proposed a semiautomatic localization
      approach that addresses this challenge, with evaluation carried out using
      anthropomorphic phantoms. To truly evaluate the algorithm's utility, the
      evaluation must be carried out using clinical data. In this article, the authors
      extend the evaluation of the approach to data sets acquired in a clinical trial.
      METHODS: Nine CBCT data sets were obtained in three interventional radiology
      procedures as part of a clinical trial evaluating a commercial navigation system.
      Fiducials were localized in the volumetric coordinate system directly from the
      projection images using the evaluated localization approach. Localization was
      assessed using two quality measures fiducial registration error to quantify
      precision and fiducial localization error to quantify accuracy. The fiducials
      used in this study are 6 mm spheres embedded in a custom registration phantom
      used by the navigation system. RESULTS: In all cases, the proposed approach was
      able to localize all five fiducial markers embedded in the registration phantom.
      The approach's mean (std) fiducial registration error was 0.29 (0.13) mm. The
      mean (std) localization difference as compared to direct volumetric localization
      was 0.82 (0.34) mm. CONCLUSIONS: Based on the current evaluation using data from
      clinical cases, the authors conclude that the localization approach is
      sufficiently accurate for use in thoracic-abdominal interventions, and that it
      can simplify the current workflow while reducing cumulative radiation to the
      patient due to repeated CBCT scans.

PMID- 21089763
TI  - Clinical development of a failure detection-based online repositioning strategy
      for prostate IMRT--experiments, simulation, and dosimetry study.
AB  - PURPOSE: To implement and evaluate clinic-ready adaptive imaging protocols for
      online patient repositioning (motion tracking) during prostate IMRT using
      treatment beam imaging supplemented by minimal, as-needed use of on-board kV.
      METHODS: The authors examine the two-step decision-making strategy: (1) Use cine
      MV imaging and online-updated characterization of prostate motion to detect
      target motion that is potentially beyond a predefined threshold and (2) use
      paired MV-kV 3D localization to determine overthreshold displacement and, if
      needed, reposition the patient. Two levels of clinical implementation were
      evaluated: (1) Field-by-field based motion correction for present-day linacs and
      (2) instantaneous repositioning for new-generation linacs with capabilities of
      simultaneous MV-kV imaging and remote automatic couch control during treatment
      delivery. Experiments were performed on a Varian Trilogy linac in clinical mode
      using a 4D motion phantom programed with prostate motion trajectories taken from
      patient data. Dosimetric impact was examined using a 2D ion chamber array.
      Simulations were done for 536 trajectories from 17 patients. RESULTS: Despite the
      loss of marker detection efficiency caused by the MLC leaves sometimes obscuring
      the field at the marker's projected position on the MV imager, the field-by-field
      correction halved (from 23% to 10%) the mean percentage of time that target
      displacement exceeded a 3 mm threshold, as compared to no intervention. This was
      achieved at minimal cost in additional imaging (average of one MV-kV pair per two
      to three treatment fractions) and with a very small number of repositionings
      (once every four to five fractions). Also with low kV usage (approximation
      2/fraction), the instantaneous repositioning approach reduced overthreshold time
      by more than 75% (23% to 5%) even with severe MLC blockage as often encountered
      in current IMRT and could reduce the overthreshold time tenfold (to < 2%) if the
      MLC blockage problem were relieved. The information acquired for repositioning
      using combined MV-kV images was found to have submillimeter accuracy.
      CONCLUSIONS: This work demonstrated with a current clinical setup that
      substantial reduction of adverse targeting effects of intrafraction prostate
      motion can be realized. The proposed adaptive imaging strategy incurs minimal
      imaging dose to the patient as compared to other stereoscopic imaging techniques.

PMID- 21089765
TI  - Prospective-gated cardiac micro-CT imaging of free-breathing mice using carbon
      nanotube field emission x-ray.
AB  - PURPOSE: Carbon nanotube (CNT) based field emission x-ray source technology has
      recently been investigated for diagnostic imaging applications because of its
      attractive characteristics including electronic programmability, fast switching,
      distributed source, and multiplexing. The purpose of this article is to
      demonstrate the potential of this technology for high-resolution prospective
      gated cardiac micro-CT imaging. METHODS: A dynamic cone-beam micro-CT scanner was
      constructed using a rotating gantry, a stationary mouse bed, a flat-panel
      detector, and a sealed CNT based microfocus x-ray source. The compact single-beam
      CNT x-ray source was operated at 50 KVp and 2 mA anode current with 100 microm x
      100 microm effective focal spot size. Using an intravenously administered
      iodinated blood-pool contrast agent, prospective cardiac and respiratory-gated
      micro-CT images of beating mouse hearts were obtained from ten anesthetized free
      breathing mice in their natural position. Four-dimensional cardiac images were
      also obtained by gating the image acquisition to different phases in the cardiac
      cycle. RESULTS: High-resolution CT images of beating mouse hearts were obtained
      at 15 ms temporal resolution and 6.2 lp/mm spatial resolution at 10% of system
      MTF. The images were reconstructed at 76 microm isotropic voxel size. The data
      acquisition time for two cardiac phases was 44 +/- 9 min. The CT values observed
      within the ventricles and the ventricle wall were 455 +/- 49 and 120 +/- 48 HU,
      respectively. The entrance dose for the acquisition of a single phase of the
      cardiac cycle was 0.10 Gy. CONCLUSIONS: A high-resolution dynamic micro-CT
      scanner was developed from a compact CNT microfocus x-ray source and its
      feasibility for prospective-gated cardiac micro-CT imaging of free-breathing mice
      under their natural position was demonstrated.

PMID- 21089766
TI  - Quantitative comparison of thermal dose models in normal canine brain.
AB  - PURPOSE: Minimally invasive thermal ablative therapies as alternatives to
      conventional surgical management of solid tumors and other pathologies is
      increasing owing to the potential benefits of performing these procedures in an
      outpatient setting with reduced complications and comorbidity. Magnetic resonance
      temperature imaging (MRTI) measurement allows existing thermal dose models to use
      the spatiotemporal temperature history to estimate the thermal damage to tissue.
      However, the various thermal dose models presented in the literature employ
      different parameters and thresholds, affecting the reliability of thermal
      dosimetry. In this study, the authors quantitatively compared three thermal dose
      models (Arrhenius rate process, CEM43, and threshold temperature) using the dice
      similarity coefficient (DSC). METHODS: The DSC was used to compare the spatial
      overlap between the region of thermal damage as predicted by the models for in
      vivo normal canine brain during thermal therapy to the region of thermal damage
      as revealed by contrast-enhanced T1-weighted images acquired immediately after
      therapy (< 20 min). The outer edge of the hyperintense rim of the ablation region
      was used as the surrogate marker for the limits of thermal coagulation. The DSC
      was also used to investigate the impact of varying the thresholds on each models'
      ability to predict the zone of thermal necrosis. RESULTS: At previously reported
      thresholds, the authors found that all three models showed good agreement
      (defined as DSC > 0.7) with post-treatment imaging. All three models examined
      across the range of commonly applied thresholds consistently showed highly
      accurate spatial overlap, low variability, and little dependence on temperature
      uncertainty. DSC values corresponding to cited thresholds were not significantly
      different from peak DSC values. CONCLUSIONS: Thus, the authors conclude that the
      all three thermal dose models can be used as a reliable surrogate for
      postcontrast tissue damage verification imaging in rapid ablation procedures and
      can also be used to enhance the capability of MRTI to control thermal therapy in
      real time.

PMID- 21089767
TI  - Dosimetric variation due to the photon beam energy in the small-animal
      irradiation: a Monte Carlo study.
AB  - PURPOSE: The impact of photon beam energy and tissue heterogeneities on dose
      distributions and dosimetric characteristics such as point dose, mean dose, and
      maximum dose was investigated in the context of small-animal irradiation using
      Monte Carlo simulations based on the EGSnrc code. METHODS: Three Monte Carlo
      mouse phantoms, namely, heterogeneous, homogeneous, and bone homogeneous were
      generated based on the same mouse computed tomography image set. These phantoms
      were generated by overriding the tissue type of none of the voxels
      (heterogeneous), all voxels (homogeneous), and only the bone voxels (bone
      homogeneous) to that of soft tissue. Phase space files of the 100 and 225 kVp
      photon beams based on a small-animal irradiator (XRad225Cx, Precision X-Ray Inc.,
      North Branford, CT) were generated using BEAMnrc. A 360 degrees photon arc was
      simulated and three-dimensional (3D) dose calculations were carried out using the
      DOSXYZnrc code through DOSCTP in the above three phantoms. For comparison, the 3D
      dose distributions, dose profiles, mean, maximum, and point doses at different
      locations such as the isocenter, lung, rib, and spine were determined in the
      three phantoms. RESULTS: The dose gradient resulting from the 225 kVp arc was
      found to be steeper than for the 100 kVp arc. The mean dose was found to be 1.29
      and 1.14 times higher for the heterogeneous phantom when compared to the mean
      dose in the homogeneous phantom using the 100 and 225 kVp photon arcs,
      respectively. The bone doses (rib and spine) in the heterogeneous mouse phantom
      were about five (100 kVp) and three (225 kVp) times higher when compared to the
      homogeneous phantom. However, the lung dose did not vary significantly between
      the heterogeneous, homogeneous, and bone homogeneous phantom for the 225 kVp
      compared to the 100 kVp photon beams. CONCLUSIONS: A significant bone dose
      enhancement was found when the 100 and 225 kVp photon beams were used in small
      animal irradiation. This dosimetric effect, due to the presence of the bone
      heterogeneity, was more significant than that due to the lung heterogeneity.
      Hence, for kV photon energies of the range used in small-animal irradiation, the
      increase of the mean and bone dose due to the photoelectric effect could be a
      dosimetric concern.

PMID- 21089768
TI  - Advanced treatment planning methods for efficient radiation therapy with laser
      accelerated proton and ion beams.
AB  - PURPOSE: Laser plasma acceleration can potentially replace large and expensive
      cyclotrons or synchrotrons for radiotherapy with protons and ions. On the way
      toward a clinical implementation, various challenges such as the maximum
      obtainable energy still remain to be solved. In any case, laser accelerated
      particles exhibit differences compared to particles from conventional
      accelerators. They typically have a wide energy spread and the beam is extremely
      pulsed (i.e., quantized) due to the pulsed nature of the employed lasers. The
      energy spread leads to depth dose curves that do not show a pristine Bragg peak
      but a wide high dose area, making precise radiotherapy impossible without an
      additional energy selection system. Problems with the beam quantization include
      the limited repetition rate and the number of accelerated particles per laser
      shot. This number might be too low, which requires a high repetition rate, or it
      might be too high, which requires an additional fluence selection system to
      reduce the number of particles. Trying to use laser accelerated particles in a
      conventional way such as spot scanning leads to long treatment times and a high
      amount of secondary radiation produced when blocking unwanted particles. METHODS:
      The authors present methods of beam delivery and treatment planning that are
      specifically adapted to laser accelerated particles. In general, it is not
      necessary to fully utilize the energy selection system to create monoenergetic
      beams for the whole treatment plan. Instead, within wide parts of the target
      volume, beams with broader energy spectra can be used to simultaneously cover
      multiple axially adjacent spots of a conventional dose delivery grid as applied
      in intensity modulated particle therapy. If one laser shot produces too many
      particles, they can be distributed over a wider area with the help of a
      scattering foil and a multileaf collimator to cover multiple lateral spot
      positions at the same time. These methods are called axial and lateral clustering
      and reduce the number of particles that have to be blocked in the beam delivery
      system. Furthermore, the optimization routine can be adjusted to reduce the
      number of dose spots and laser shots. The authors implemented these methods into
      a research treatment planning system for laser accelerated particles. RESULTS:
      The authors' proposed methods can decrease the amount of secondary radiation
      produced when blocking particles with wrong energies or when reducing the total
      number of particles from one laser shot. Additionally, caused by the efficient
      use of the beam, the treatment time is reduced considerably. Both improvements
      can be achieved without extensively changing the quality of the treatment plan
      since conventional intensity modulated particle therapy usually includes a
      certain amount of unused degrees of freedom which can be used to adapt to laser
      specific properties. CONCLUSIONS: The advanced beam delivery and treatment
      planning methods reduce the need to have a perfect laser-based accelerator
      reproducing the properties of conventional accelerators that might not be
      possible without increasing treatment time and secondary radiation to the
      patient. The authors show how some of the differences to conventional beams can
      be overcome and efficiently used for radiation treatment.

PMID- 21089769
TI  - A support vector machine (SVM) for predicting preferred treatment position in
      radiotherapy of patients with breast cancer.
AB  - PURPOSE: NYU 05-181 protocol compared the CT simulation in both supine and prone
      positions for 400 patients with breast cancer (200 left-breast and 200 right
      breast) to identify which setup is better at sparing heart and lung involvement
      in the treatment process. The results demonstrated that all right-breast patients
      benefited from the prone treatment position, while for left-breast patients, 85%
      were better treated prone and 15% were better treated supine. Using the clinical
      data collected from this protocol, the authors aimed at developing an automated
      tool capable of identifying which of the left-breast cancer patients are better
      treated supine without obtaining a second CT scan in the supine position.
      METHODS: Prone CT scans from 198 of the 200 left-breast cancer patients enrolled
      in NYU 05-181 protocol were deidentified and exported to a dedicated research
      planning workstation. Three-dimensional geometric features of the organs at risk
      and tumor bed were extracted. A two-stage classifier was used to classify
      patients into the prone class or the supine class. In the first stage, the
      authors use simple thresholding to divide the patients into two groups based on
      their in-field heart volume. For patients with in-field heart volume < or = 0.1
      cc, the prone position was chosen as the preferred treatment position. Patients
      with in-field heart volume > 0.1 cc will be further classified in the second
      stage by a weighted support vector machine (SVM). The weight parameters of the
      SVM were adjusted to maximize the specificity [true-supine/(true-supine+false
      prone)] at the cost of lowering but still maintaining reasonable sensitivity
      [true-prone/(true-prone+false-supine)]. The authors used K-fold cross validations
      to test the performance of the SVM classifier. A feature selection algorithm was
      also used to identify features that give the best classification performance.
      RESULTS: After the first stage, 49 of the 198 left-breast cancer patients were
      found to have > 0.1 cc of in-field heart volume. The three geometric features of
      heart orientation, distance between heart and tumor, and in-field lung were
      selected by the feature selection algorithm in the second stage of the two-stage
      classifier to give the best predefined weighted accuracy. The overall sensitivity
      and specificity of the proposed method were found to be 90.4% and 99.3%,
      respectively. Using two-stage classification, the authors reduced the proportion
      of prone-treated patients that need a second supine CT scan down to 16.3/170 or
      9.6%, as compared to 21/170 or 12.4% when the authors use only the first stage
      (thresholding) for classification. CONCLUSIONS: The authors' study showed that a
      feature-based classifier is feasible for predicting the preferred treatment
      position, based on features extracted from prone CT scans. The two-stage
      classifier achieved very high specificity at an acceptable expense of
      sensitivity.

PMID- 21089770
TI  - A new method to combine 3D reconstruction volumes for multiple parallel circular
      cone beam orbits.
AB  - PURPOSE: This article presents a new reconstruction method for 3D imaging using a
      multiple 360 degrees circular orbit cone beam CT system, specifically a way to
      combine 3D volumes reconstructed with each orbit. The main goal is to improve the
      noise performance in the combined image while avoiding cone beam artifacts.
      METHODS: The cone beam projection data of each orbit are reconstructed using the
      FDK algorithm. When at least a portion of the total volume can be reconstructed
      by more than one source, the proposed combination method combines these overlap
      regions using weighted averaging in frequency space. The local exactness and the
      noise performance of the combination method were tested with computer simulations
      of a Defrise phantom, a FORBILD head phantom, and uniform noise in the raw data.
      RESULTS: A noiseless simulation showed that the local exactness of the
      reconstructed volume from the source with the smallest tilt angle was preserved
      in the combined image. A noise simulation demonstrated that the combination
      method improved the noise performance compared to a single orbit reconstruction.
      CONCLUSIONS: In CT systems which have overlap volumes that can be reconstructed
      with data from more than one orbit and in which the spatial frequency content of
      each reconstruction can be calculated, the proposed method offers improved noise
      performance while keeping the local exactness of data from the source with the
      smallest tilt angle.

PMID- 21089771
TI  - Hyperpolarized 13C MRS surface coil: design and signal-to-noise ratio estimation.
AB  - PURPOSE: Hyperpolarized carbon-13 magnetic resonance spectroscopy is a novel and
      powerful tool for exploring the metabolic state of tissue, but a number of
      technological problems still limit this technology and need innovative solutions.
      In particular, the low molar concentration of derivate metabolites give rise to
      low signal-to-noise ratio (SNR), which makes the design and development of
      dedicated RF coils a task of fundamental importance. In this article, the authors
      describe the simulation and the design of a dedicated 13C surface coil for
      cardiac metabolism assessment in pig models. METHODS: A SNR model for a circular
      loop is presented and applied to the design of a 13C coil which guarantees the
      desired field-of-view and provides high SNR with a good penetration in deep
      sample regions. The coil resistance was calculated from Ohm's law and the
      magnetic field pattern was calculated using Biot-Savart law, while the sample
      induced resistance was calculated using a numerical finite-difference time-domain
      algorithm. Successively, a prototype of the coil was built and tested on the
      workbench and by acquisition of MR data. RESULTS: The comparison of SNR-vs-depth
      profiles between the theoretical SNR model and the experimental SNR extracted
      from the phantom chemical shift image (CSI) showed the accuracy of the authors'
      model. Moreover, the authors demonstrated the use of the coil for the acquisition
      of a CSI of a hyperpolarized [1-13C] pyruvate phantom. CONCLUSIONS: The results
      demonstrated the design trade-offs to successfully design a dedicated coil for
      cardiac imaging in the pig with hyperpolarized 13C by developing a SNR model
      which allows the prediction of the coil performance. This approach can be
      employed for deriving SNR formulations for coil with more complex geometries.

PMID- 21089772
TI  - Monte Carlo calculated TG-60 dosimetry parameters for the beta- emitter 153Sm
      brachytherapy source.
AB  - PURPOSE: The formalism recommended by Task Group 60 (TG-60) of the American
      Association of Physicists in Medicine (AAPM) is applicable for beta sources.
      Radioactive biocompatible and biodegradable 153Sm glass seed without
      encapsulation is a beta- emitter radionuclide with a short half-life and delivers
      a high dose rate to the tumor in the millimeter range. This study presents the
      results of Monte Carlo calculations of the dosimetric parameters for the 153Sm
      brachytherapy source. METHODS: Version 5 of the (MCNP) Monte Carlo radiation
      transport code was used to calculate two-dimensional dose distributions around
      the source. The dosimetric parameters of AAPM TG-60 recommendations including the
      reference dose rate, the radial dose function, the anisotropy function, and the
      one-dimensional anisotropy function were obtained. RESULTS: The dose rate value
      at the reference point was estimated to be 9.21 +/- 0.6 cGy h(-1) microCi(-1).
      Due to the low energy beta emitted from 153Sm sources, the dose fall-off profile
      is sharper than the other beta emitter sources. The calculated dosimetric
      parameters in this study are compared to several beta and photon emitting seeds.
      CONCLUSIONS: The results show the advantage of the 153Sm source in comparison
      with the other sources because of the rapid dose fall-off of beta ray and high
      dose rate at the short distances of the seed. The results would be helpful in the
      development of the radioactive implants using 153Sm seeds for the brachytherapy
      treatment.

PMID- 21089773
TI  - Apparent absence of a proton beam dose rate effect and possible differences in
      RBE between Bragg peak and plateau.
AB  - PURPOSE: Respiration-gated irradiation for a moving target requires a longer time
      to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate
      (UDR) proton beam, which is 10-100 times higher than that is used in current
      clinical practice, has been investigated to deliver daily dose in single breath
      hold duration. The purpose of this study is to investigate the survival curve and
      relative biological effectiveness (RBE) of such an ultrahigh dose rate proton
      beam and their linear energy transfer (LET) dependence. METHODS: HSG cells were
      irradiated by a spatially and temporally uniform proton beam at two different
      dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh
      dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau.
      To study LET dependence, the cells were positioned at the Bragg peak, where the
      absorbed dose-averaged LET was 3.19 keV/microm, and at the plateau, where it was
      0.56 keV/microm. After the cell exposure and colony assay, the measured data were
      fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10%
      survival were compared. RESULTS: No significant difference was observed in the
      survival curves between the two proton dose rates. The ratio of the RBE for
      CDR/UDR was 0.98 +/- 0.04 at the Bragg peak and 0.96 +/- 0.06 at the plateau. On
      the other hand, Bragg peak/plateau RBE ratio was 1.15 +/- 0.05 for UDR and 1.18
      +/- 0.07 for CDR. CONCLUSIONS: Present RBE can be consistently used in treatment
      planning of PRT using ultrahigh dose rate radiation. Because a significant
      increase in RBE toward the Bragg peak was observed for both UDR and CDR, further
      evaluation of RBE enhancement toward the Bragg peak and beyond is required.

PMID- 21089774
TI  - Regularized antenna profile adaptation in online hyperthermia treatment.
AB  - PURPOSE: Online optimization of annular-phased-array hyperthermia (HT) is based
      on planning tools and magnetic resonance (MR) thermometry. Until now, the method
      has been validated in phantoms. Further developments and extensions are required
      for clinical purposes. In particular, the problem of deducing the electric field
      distribution inside the patient from MR thermometry is ill-posed, which leads to
      an amplification of measurement errors. A method to overcome this difficulty is
      proposed. METHODS: The authors utilized a regularized Gauss-Newton algorithm with
      a fast bioheat transfer equation (BHTE) approximation to identify the field
      parameters. To evaluate the method, simulations with patient models are conducted
      and a treatment data set obtained from a heat treatment performed in the hybrid
      HT-MR system at the Charite Medical School is used to visualize the error
      amplification. RESULTS: The regularization leads to a significantly improved
      accuracy of the predicted electric fields and temperatures compared to an
      unregularized approach. The BHTE approximation enables highly accurate
      temperature predictions in real-time. CONCLUSIONS: Regularization proves to be
      necessary to identify electromagnetic field parameters. The proposed method is
      able to reproduce measurements without overfitting to the noise in the MR
      measurements and results in an improved treatment planning.

PMID- 21089775
TI  - Shading correction for on-board cone-beam CT in radiation therapy using planning
      MDCT images.
AB  - PURPOSE: Applications of cone-beam CT (CBCT) to image-guided radiationtherapy
      (IGRT) are hampered by shading artifacts in the reconstructed images. These
      artifacts are mainly due to scatter contamination in the projections but also can
      result from uncorrected beam hardening effects as well as nonlinearities in
      responses of the amorphous silicon flat panel detectors. While currently, CBCT is
      mainly used to provide patient geometry information for treatment setup, more
      demanding applications requiring high-quality CBCT images are under
      investigation. To tackle these challenges, many CBCT correction algorithms have
      been proposed; yet, a standard approach still remains unclear. In this work, we
      propose a shading correction method for CBCT that addresses artifacts from low
      frequency projection errors. The method is consistent with the current workflow
      of radiation therapy. METHODS: With much smaller inherent scatter signals and
      more accurate detectors, diagnostic multidetector CT (MDCT) provides high quality
      CT images that are routinely used for radiation treatment planning. Using the
      MDCT image as "free" prior information, we first estimate the primary projections
      in the CBCT scan via forward projection of the spatially registered MDCT data.
      Since most of the CBCT shading artifacts stem from low-frequency errors in the
      projections such as scatter, these errors can be accurately estimated by low-pass
      filtering the difference between the estimated and raw CBCT projections. The
      error estimates are then subtracted from the raw CBCT projections. Our method is
      distinct from other published correction methods that use the MDCT image as a
      prior because it is projection-based and uses limited patient anatomical
      information from the MDCT image. The merit of CBCT-based treatment monitoring is
      therefore retained. RESULTS: The proposed method is evaluated using two phantom
      studies on tabletop systems. On the Catphan 600 phantom, our approach reduces the
      reconstruction error from 348 Hounsfield unit (HU) without correction to 4 HU
      around the object center after correction, and from 375 HU to 17 HU in the high
      contrast regions. In the selected regions of interest (ROIs), the average image
      contrast is increased by a factor of 3.3. When noise suppression is implemented,
      the proposed correction substantially improves the contrast-to-noise ratio (CNR)
      and therefore the visibility of low-contrast objects, as seen in a more
      challenging pelvis phantom study. Besides a significant improvement in image
      uniformity, a low-contrast object of approximately 25 HU, which is otherwise
      buried in the shading artifacts, can be clearly identified after the proposed
      correction due to a CNR increase of 3.1. Compared to a kernel-based scatter
      correction method coupled with an analytical beam hardening correction, our
      approach also shows an overall improved performance with some residual artifacts.
      CONCLUSIONS: By providing effective shading correction, our approach has the
      potential to improve the accuracy of more advanced CBCT-based clinical
      applications for IGRT, such as tumor delineation and dose calculation.

PMID- 21089776
TI  - Direct measurement of instantaneous source speed for a HDR brachytherapy unit
      using an optical fiber based detector.
AB  - PURPOSE: Several attempts to determine the transit time of a high dose rate (HDR)
      brachytherapy unit have been reported in the literature with controversial
      results. The determination of the source speed is necessary to accurately
      calculate the transient dose in brachytherapy treatments. In these studies, only
      the average speed of the source was measured as a parameter for transit dose
      calculation, which does not account for the realistic movement of the source, and
      is therefore inaccurate for numerical simulations. The purpose of this work is to
      report the implementation and technical design of an optical fiber based detector
      to directly measure the instantaneous speed profile of a 192Ir source in a
      Nucletron HDR brachytherapy unit. METHODS: To accomplish this task, we have
      developed a setup that uses the Cerenkov light induced in optical fibers as a
      detection signal for the radiation source moving inside the HDR catheter. As the
      192Ir source travels between two optical fibers with known distance, the
      threshold of the induced signals are used to extract the transit time and thus
      the velocity. The high resolution of the detector enables the measurement of the
      transit time at short separation distance of the fibers, providing the
      instantaneous speed. RESULTS: Accurate and high resolution speed profiles of the
      192Ir radiation source traveling from the safe to the end of the catheter and
      between dwell positions are presented. The maximum and minimum velocities of the
      source were found to be 52.0 +/- 1.0 and 17.3 +/- 1.2 cm/s. The authors
      demonstrate that the radiation source follows a uniformly accelerated linear
      motion with acceleration of [a] = 113 cm/s2. In addition, the authors compare the
      average speed measured using the optical fiber detector to those obtained in the
      literature, showing deviation up to 265%. CONCLUSIONS: To the best of the
      authors' knowledge, the authors directly measured for the first time the
      instantaneous speed profile of a radiation source in a HDR brachytherapy unit
      traveling from the unit safe to the end of the catheter and between interdwell
      distances. The method is feasible and accurate to implement on quality assurance
      tests and provides a unique database for efficient computational simulations of
      the transient dose.

PMID- 21089777
TI  - Multiple-stepped Zeeman field offset method applied in acquiring enhanced
      resolution spin-echo electron paramagnetic resonance images.
AB  - PURPOSE: Electron paramagnetic resonance (EPR) imaging techniques provide
      quantitative in vivo oxygen distribution images. Time-domain techniques including
      electron spin echo (ESE) imaging have been under study in recent years for their
      robustness and promising new features. One of the limitations of ESE imaging
      addressed here is the finite acquisition frequency bandwidth, which imposes
      limits on applied magnetic field gradients and the resulting image spatial
      resolution. In order to improve the image spatial resolution, we have extended
      the effective frequency bandwidth of the imaging system by acquiring projections
      at multiple Zeeman magnetic field offsets and combining them to restore complete
      projections obtained with more uniform frequency response, resulting in higher
      quality images. METHODS: In multiple-stepped magnetic field or multi-B scheme,
      every projection of the three dimensional object is acquired at different main or
      Zeeman magnetic field (B) offset values. The data from field offset steps are
      combined, normalizing to the imaging system frequency acquisition window
      function, a sensitivity profile, to restore the complete projection. A
      multipurpose pulse EPR imager and phantoms containing the same type of spin probe
      (OX063H) used in routine animal imaging were also used in this study. RESULTS:
      Using the multi-B method, we were able to acquire images of our phantoms with
      enhanced spatial resolution compared to the conventional ESE approach. Compared
      to standard single-B ESE images, the T2 resolutions of multi-B images were
      superior using a high spatial-resolution regime. Image artifacts present in high
      gradient single-B ESE images are also substantially reduced using in the multi-B
      scheme. CONCLUSIONS: The multi-B method is less susceptible to instrumental
      limitations for larger gradient fields and acquiring images with higher spatial
      resolution better overall quality, without the need to alter the existing pulse
      ESE image acquisition hardware.

PMID- 21089778
TI  - Characterization of a real-time surface image-guided stereotactic positioning
      system.
AB  - PURPOSE: The AlignRT3C system is an image-guided stereotactic positioning system
      (IGSPS) that provides real-time target localization. This study involves the
      first use of this system with three camera pods. The authors have evaluated its
      localization accuracy and tracking ability using a cone-beam computed tomography
      (CBCT) system and an optical tracking system in a clinical setting. METHODS: A
      modified Rando head-and-neck phantom and five patients receiving intracranial
      stereotactic radiotherapy (SRT) were used to evaluate the calibration,
      registration, and position-tracking accuracies of the AlignRT3C system and to
      study surface reconstruction uncertainties, including the effects due to
      interfractional and intrafractional motion, skin tone, room light level, camera
      temperature, and image registration region of interest selection. System accuracy
      was validated through comparison with the Elekta kV CBCT system (XVI) and the
      Varian frameless SonArray (FSA) optical tracking system. Surface-image data sets
      were acquired with the AlignRT3C daily for the evaluation of pretreatment and
      interfractional and intrafractional motion for each patient. Results for two
      different reference image sets, planning CT surface contours (CTS) and previously
      recorded AlignRT3C optical surface images (ARTS), are reported. RESULTS: The
      system origin displacements for the AlignRT3C and XVI systems agreed to within
      1.3 mm and 0.7 degrees. Similar results were seen for AlignRT3C vs FSA. For the
      phantom displacements having couch angles of 0 degrees, those that utilized ART_S
      references resulted in a mean difference of 0.9 mm/0.4 degrees with respect to
      XVI and 0.3 mm/0.2 degrees with respect to FSA. For phantom displacements of more
      than +/- 10 mm and +/- 3 degrees, the maximum discrepancies between AlignRT and
      the XVI and FSA systems were 3.0 and 0.4 mm, respectively. For couch angles up to
      +/- 90 degrees, the mean (max.) difference between the AlignRT3C and FSA was 1.2
      (2.3) mm/0.7 degrees (1.2 degrees). For all tests, the mean registration errors
      obtained using the CT_S references were approximately 1.3 mm/1.0 degrees larger
      than those obtained using the ART_S references. For the patient study, the mean
      differences in the pretreatment displacements were 0.3 mm/0.2 degrees between the
      AlignRT3C and XVI systems and 1.3 mm/1 degrees between the FSA and XVI systems.
      For noncoplanar treatments, interfractional motion displacements obtained using
      the ART_S and CT_S references resulted in 90th percentile differences within 2.1
      mm/0.8 degrees and 3.3 mm/0.3 degrees, respectively, compared to the FSA system.
      Intrafractional displacements that were tracked for a maximum of 14 min were
      within 1 mm/1 degrees of those obtained with the FSA system. Uncertainties
      introduced by the bite-tray were as high as 3 mm/2 degrees for one patient. The
      combination of gantry, aSi detector panel, and x-ray tube blockage effects during
      the CBCT acquisition resulted in a registration error of approximately 3 mm. No
      skin-tone or surface deformation effects were seen with the limited patient
      sample. CONCLUSIONS: AlignRT3C can be used as a nonionizing IGSPS with accuracy
      comparable to current image/marker-based systems. IGSPS and CBCT can be combined
      for high-precision positioning without the need for patient-attached localization
      devices.

PMID- 21089779
TI  - Noninvasive mapping of spontaneous fluctuations in tumor oxygenation using 19F
      MRI.
AB  - PURPOSE: Acute hypoxia (transient cycles of hypoxia-reoxygenation) is known to
      occur in solid tumors and may be a poorly appreciated therapeutic problem as it
      can be associated with resistance to radiation therapy, impaired delivery of
      chemotherapeutic agents, or metastasis development. The objective of the present
      study was to use MR 19F relaxometry maps to analyze the spontaneous fluctuations
      of partial pressure of oxygen (pO2) over time in experimental tumors. METHODS:
      The pO2 maps were generated after direct intratumoral administration of a
      fluorine compound (hexafluorobenzene) whose relaxation rate (1/T1) is
      proportional to the % O2. The authors used a SNAP inversion-recovery sequence at
      4.7 T to acquire parametric images of the T1 relaxation time with a high spatial
      and temporal resolution. Homemade routines were developed to perform regions of
      interest analysis, as well as pixel by pixel analysis of pO2 over time. RESULTS:
      The authors were able to quantify and probe the heterogeneity of spontaneous
      fluctuations in tumor pO2: (i) Spontaneous fluctuations in pO2 occurred
      regardless of the basal oxygenation state (i.e., both in oxygenated and in
      hypoxic regions) and (ii) spontaneous fluctuations occurred at a rate of 1
      cycle/12-47 min. For validation, the analysis was performed in dead mice for
      which acute changes did not occur. The authors thereby demonstrated that 19F MRI
      technique is sensitive to acute change in pO2 in tumors. CONCLUSIONS: This is the
      first approach that allows quantitative minimally invasive measurement of the
      spontaneous fluctuations of tumor oxygenation using a look-locker approach (e.g.,
      SNAP IR). This approach could be an important tool to characterize the phenomenon
      of tumor acute hypoxia, to understand its physiopathology, and to improve
      therapies.

PMID- 21089780
TI  - Model-based calculations of off-axis ratio of conic beams for a dedicated 6 MV
      radiosurgery unit.
AB  - PURPOSE: Because the small-radius photon beams shaped by cones in stereotactic
      radiosurgery (SRS) lack lateral electronic equilibrium and a detector's finite
      cross section, direct experimental measurement of dosimetric data for these beams
      can be subject to large uncertainties. As the dose calculation accuracy of a
      treatment planning system largely depends on how well the dosimetric data are
      measured during the machine's commissioning, there is a critical need for an
      independent method to validate measured results. Therefore, the authors studied
      the model-based calculation as an approach to validate measured off-axis ratios
      (OARs). METHODS: The authors previously used a two-component analytical model to
      calculate central axis dose and associated dosimetric data (e.g., scatter factors
      and tissue-maximum ratio) in a water phantom and found excellent agreement
      between the calculated and the measured central axis doses for small 6 MV SRS
      conic beams. The model was based on that of Nizin and Mooij ["An approximation of
      central-axis absorbed dose in narrow photon beams," Med. Phys. 24, 1775-1780
      (1997)] but was extended to account for apparent attenuation, spectral
      differences between broad and narrow beams, and the need for stricter scatter
      dose calculations for clinical beams. In this study, the authors applied Clarkson
      integration to this model to calculate OARs for conic beams. OARs were calculated
      for selected cones with radii from 0.2 to 1.0 cm. To allow comparisons, the
      authors also directly measured OARs using stereotactic diode (SFD), microchamber,
      and film dosimetry techniques. The calculated results were machine-specific and
      independent of direct measurement data for these beams. RESULTS: For these conic
      beams, the calculated OARs were in excellent agreement with the data measured
      using an SFD. The discrepancies in radii and in 80%-20% penumbra were within 0.01
      cm, respectively. Using SFD-measured OARs as the reference data, the authors
      found that the calculated OARs were more accurate than those measured with a
      microchamber or film dosimetry. CONCLUSIONS: The model produces sufficiently
      accurate conic beam dosimetric data that can be used to validate direct
      measurement results for such beams.

PMID- 21089781
TI  - Experimental determination of the radial dose distribution in high gradient
      regions around 192Ir wires: comparison of electron paramagnetic resonance
      imaging, films, and Monte Carlo simulations.
AB  - PURPOSE: The experimental determination of doses at proximal distances from
      radioactive sources is difficult because of the steepness of the dose gradient.
      The goal of this study was to determine the relative radial dose distribution for
      a low dose rate 192Ir wire source using electron paramagnetic resonance imaging
      (EPRI) and to compare the results to those obtained using Gafchromic EBT film
      dosimetry and Monte Carlo (MC) simulations. METHODS: Lithium formate and ammonium
      formate were chosen as the EPR dosimetric materials and were used to form
      cylindrical phantoms. The dose distribution of the stable radiation-induced free
      radicals in the lithium formate and ammonium formate phantoms was assessed by
      EPRI. EBT films were also inserted inside in ammonium formate phantoms for
      comparison. MC simulation was performed using the MCNP4C2 software code. RESULTS:
      The radical signal in irradiated ammonium formate is contained in a single narrow
      EPR line, with an EPR peak-to-peak linewidth narrower than that of lithium
      formate (approximately 0.64 and 1.4 mT, respectively). The spatial resolution of
      EPR images was enhanced by a factor of 2.3 using ammonium formate compared to
      lithium formate because its linewidth is about 0.75 mT narrower than that of
      lithium formate. The EPRI results were consistent to within 1% with those of
      Gafchromic EBT films and MC simulations at distances from 1.0 to 2.9 mm. The
      radial dose values obtained by EPRI were about 4% lower at distances from 2.9 to
      4.0 mm than those determined by MC simulation and EBT film dosimetry.
      CONCLUSIONS: Ammonium formate is a suitable material under certain conditions for
      use in brachytherapy dosimetry using EPRI. In this study, the authors
      demonstrated that the EPRI technique allows the estimation of the relative radial
      dose distribution at short distances for a 192Ir wire source.

PMID- 21089782
TI  - Monte Carlo evaluation of scatter mitigation strategies in cone-beam CT.
AB  - PURPOSE: To investigate the efficacy of two widely used scatter mitigation
      methods: antiscatter grids (ASGs) and beam modulating with bowtie filters (BTFs),
      in combination with subtractive scatter correction or zeroth order normalization
      phantom calibration, for improving image noise, contrast, contrast-to-noise ratio
      (CNR), and image uniformity for on-board cone-beam CT (CBCT) imaging systems used
      for image-guided radiation therapy. METHODS: PTRAN Monte Carlo CBCT x-ray
      projections of head and pelvic phantoms were calculated for combinations of beam
      modulation and scatter rejection methods and images were reconstructed by in
      house developed software. In addition, a simple one-dimensional analytic model
      was developed to predict scatter-to-primary ratio (SPR) and CNR as a function of
      cylindrical phantom thickness, ASG transmission, and beam modulation with bow-tie
      filters. RESULTS: ASGs were found to have slightly negative or no effect on head
      phantom image CNR and to modestly improve CNR (10%-20%) in pelvic phantom images.
      However, scatter subtraction and norm-phantom calibration perform better when
      applied on data acquired with ASGs. Scatter subtraction improves CT number
      accuracy, but increases noise, and in high SPR/low primary-photon transmission
      scenarios can dramatically reduce CNR and introduce streaking artifacts. The BTF
      is found to reduce SPR and image noise, resulting in a better trade-off between
      CNR and imaging dose, but introduces a circular band artifact. CONCLUSIONS: Our
      study shows that ASGs have a modest positive impact in pelvic scans and negative
      in head scans, scatter subtraction improves the HU accuracy but reduces CNR,
      while BTF has a clearly positive effect.

PMID- 21089784
TI  - Normalized metal artifact reduction (NMAR) in computed tomography.
AB  - PURPOSE: While modern clinical CT scanners under normal circumstances produce
      high quality images, severe artifacts degrade the image quality and the
      diagnostic value if metal prostheses or other metal objects are present in the
      field of measurement. Standard methods for metal artifact reduction (MAR) replace
      those parts of the projection data that are affected by metal (the so-called
      metal trace or metal shadow) by interpolation. However, while sinogram
      interpolation methods efficiently remove metal artifacts, new artifacts are often
      introduced, as interpolation cannot completely recover the information from the
      metal trace. The purpose of this work is to introduce a generalized normalization
      technique for MAR, allowing for efficient reduction of metal artifacts while
      adding almost no new ones. The method presented is compared to a standard MAR
      method, as well as MAR using simple length normalization. METHODS: In the first
      step, metal is segmented in the image domain by thresholding. A 3D forward
      projection identifies the metal trace in the original projections. Before
      interpolation, the projections are normalized based on a 3D forward projection of
      a prior image. This prior image is obtained, for example, by a multithreshold
      segmentation of the initial image. The original rawdata are divided by the
      projection data of the prior image and, after interpolation, denormalized again.
      Simulations and measurements are performed to compare normalized metal artifact
      reduction (NMAR) to standard MAR with linear interpolation and MAR based on
      simple length normalization. RESULTS: Promising results for clinical spiral cone
      beam data are presented in this work. Included are patients with hip prostheses,
      dental fillings, and spine fixation, which were scanned at pitch values ranging
      from 0.9 to 3.2. Image quality is improved considerably, particularly for metal
      implants within bone structures or in their proximity. The improvements are
      evaluated by comparing profiles through images and sinograms for the different
      methods and by inspecting ROIs. NMAR outperforms both other methods in all cases.
      It reduces metal artifacts to a minimum, even close to metal regions. Even for
      patients with dental fillings, which cause most severe artifacts, satisfactory
      results are obtained with NMAR. In contrast to other methods, NMAR prevents the
      usual blurring of structures close to metal implants if the metal artifacts are
      moderate. CONCLUSIONS: NMAR clearly outperforms the other methods for both
      moderate and severe artifacts. The proposed method reliably reduces metal
      artifacts from simulated as well as from clinical CT data. Computationally
      efficient and inexpensive compared to iterative methods, NMAR can be used as an
      additional step in any conventional sinogram inpainting-based MAR method.

PMID- 21089783
TI  - Deformable left-ventricle mesh model for motion-compensated filtering in cardiac
      gated SPECT.
AB  - PURPOSE: In this article, the authors present a motion-compensated spatiotemporal
      processing algorithm to reduce noise in cardiac gated SPECT. Cardiac gated SPECT
      data are particularly noisy because the acquired photon data are divided among a
      number of time frames (gates). Classical spatial reconstruction and processing
      techniques offer noise reduction but they are usually applied on each frame
      separately and fail to utilize temporal correlation between frames. METHODS: In
      this work, the authors present a motion-compensated spatiotemporal
      postreconstruction filter offering noise reduction while minimizing motion-blur
      artifacts. The proposed method can be used regardless of the type of image
      reconstruction method (analytical or iterative). The between-frame volumetric
      myocardium motion is estimated using a deformable mesh model based on the model
      of the myocardial surfaces. The estimated motion is then used to perform
      spatiotemporal filtering along the motion trajectories. Both the motion
      estimation and spatiotemporal filtering methods seek to maintain the wall
      brightening seen during cardiac contraction. Wall brightening is caused by the
      partial volume effect, which is usually viewed as an artifact; however, wall
      brightening is a useful signature in clinical practice because it allows the
      clinician to visualize wall thickening. Therefore, the authors seek in their
      method to preserve the brightening effect. RESULTS: The authors find that the
      proposed method offers better noise reduction than several existing methods as
      quantitatively evaluated by signal-to-noise ratio, bias-variance plots, and
      ejection fraction analysis as well as on tested clinical data. CONCLUSIONS: The
      proposed method mitigates for noise in cardiac gated SPECT images using a
      postreconstruction motion-compensated filtering approach. Visual as well as
      quantitative evaluation show considerable improvement in image quality.

PMID- 21089785
TI  - Effects of multiple-interaction photon events in a high-resolution PET system
      that uses 3-D positioning detectors.
AB  - PURPOSE: The authors' laboratory is developing a dual-panel, breast-dedicated PET
      system. The detector panels are built from dual-LSO-position-sensitive avalanche
      photodiode (PSAPD) modules-units holding two 8 x 8 arrays of 1 mm3 LSO crystals,
      where each array is coupled to a PSAPD. When stacked to form an imaging volume,
      these modules are capable of recording the 3-D coordinates of individual
      interactions of a multiple-interaction photon event (MIPE). The small size of the
      scintillation crystal elements used increases the likelihood of photon scattering
      between crystal arrays. In this article, the authors investigate how MIPEs impact
      the system photon sensitivity, the data acquisition scheme, and the quality and
      quantitative accuracy of reconstructed PET images. METHODS: A Monte Carlo
      simulated PET scan using the dual-panel system was performed on a uniformly
      radioactive phantom for the photon sensitivity study. To establish the impact of
      MIPEs on a proposed PSAPD multiplexing scheme, experimental data were collected
      from a dual-LSO-PSAPD module edge-irradiated with a 22Na point source, the data
      were compared against simulation data based on an identical setup. To assess the
      impact of MIPEs on the dual-panel PET images, a simulated PET of a phantom
      comprising a matrix of hot spherical radiation sources of varying diameters
      immersed in a warm background was performed. The list-mode output data were used
      for image reconstruction, where various methods were used for estimating the
      location of the first photon interaction in MIPEs for more accurate line of
      response positioning. The contrast recovery coefficient (CRC), contrast to noise
      ratio (CNR), and the full width at half maximum spatial resolution of the spheres
      in the reconstructed images were used as figures of merit to facilitate
      comparison. RESULTS: Compared to image reconstruction employing only events with
      interactions confined to one LSO array, a potential single photon sensitivity
      gain of > 46.9% (> 115.7% for coincidence) was noted for a uniform phantom when
      MIPEs with summed-energy falling within a +/- 12% window around the photopeak
      were also included. Both experimental and simulation data demonstrate that < 0.4%
      of the events whose summed-energy deposition falling within that energy window
      interacted with both crystal arrays within the same dual-LSO-PSAPD module. This
      result establishes the feasibility of a proposed multiplexed readout of analog
      output signals of the two PSAPDs within each module. Using MIPEs with summed
      energy deposition within the 511 keV +/- 12% photopeak window and a new method
      for estimating the location of the first photon interaction in MIPEs, the
      corresponding reconstructed image exhibited a peak CNR of 7.23 for the 8 mm
      diameter phantom spheres versus a CNR of 6.69 from images based solely on single
      LSO array interaction events. The improved system photon sensitivity could be
      exploited to reduce the scan time by up to approximately 10%, while still
      maintaining image quality comparable to that achieved if MIPEs were excluded.
      CONCLUSIONS: MIPE distribution in the detectors allows the proposed photodetector
      multiplexing arrangement without significant information loss. Furthermore,
      acquiring MIPEs can enhance system photon sensitivity and improve PET image CNR
      and CRC. The system under development can therefore competently acquire and
      analyze MIPEs and produce high-resolution PET images.

PMID- 21089786
TI  - Surface applicator calibration and commissioning of an electronic brachytherapy
      system for nonmelanoma skin cancer treatment.
AB  - PURPOSE: The Xoft Axxent x-ray source has been used for treating nonmelanoma skin
      cancer since the surface applicators became clinically available in 2009. The
      authors report comprehensive calibration procedures for the electronic
      brachytherapy (eBx) system with the surface applicators. METHODS: The Xoft
      miniature tube (model S700) generates 50 kVp low-energy x rays. The new surface
      applicators are available in four sizes of 10, 20, 35, and 50 mm in diameter. The
      authors' tests include measurements of dose rate, air-gap factor, output
      stability, depth dose verification, beam flatness and symmetry, and treatment
      planning with patient specific cutout factors. The TG-61 in-air method was used
      as a guideline for acquiring nominal dose-rate output at the skin surface. A soft
      x-ray parallel-plate chamber (PTW T34013) and electrometer was used for the
      output commissioning. GafChromic EBT films were used for testing the properties
      of the treatment fields with the skin applicators. Solid water slabs were used to
      verify the depth dose and cutout factors. Patients with basal cell or squamous
      cell carcinoma were treated with eBx using a calibrated Xoft system with the low
      energy x-ray source and the skin applicators. RESULTS: The average nominal dose
      rate output at the skin surface for the 35 mm applicator is 1.35 Gy/min with +/-
      5% variation for 16 sources. The dose-rate output and stability (within +/- 5%
      variation) were also measured for the remaining three applicators. For the same
      source, the output variation is within 2%. The effective source-surface distance
      was calculated based on the air-gap measurements for four applicator sizes. The
      field flatness and symmetry are well within 5%. Percentage depth dose in water
      was provided by factory measurements and can be verified using solid water slabs.
      Treatment duration was calculated based on the nominal dose rate, the
      prescription fraction size, the depth dose percentage, and the cutout factor. The
      output factor needs to be measured for each case with varying shapes of cutouts.
      CONCLUSIONS: Together with TG-61, the authors' methodology provides comprehensive
      calibration procedures for medical physicists for using the Xoft eBx system and
      skin applicators for nonmelanoma skin cancer treatments.

PMID- 21089787
TI  - Virtual eversion and rotation of colon based on outer surface centerline.
AB  - PURPOSE: Virtual eversion turns the colon's inner surface to its outside while
      maintaining the original colon path. The virtually everted colon allows both
      global and local views of the mucosal surface for observation. However, the
      conventional colon's inner surface centerline commonly used in virtual
      colonoscopy and virtual flattening is not suitable for virtual eversion.
      Therefore, the colon's outer surface centerline is introduced for virtual
      eversion to produce a more accurate representation. METHODS: An improved level
      set segmentation method is presented for generating the colon's outer surface. To
      achieve eversion with fewer errors, the centerline of the colon's outer surface
      is employed in the proposed virtual eversion method instead of the inner surface
      centerline. A hybrid sampling method is designed to accelerate the eversion.
      Virtual rotation is introduced to visualize the lateral and rear views of the
      colon better. The gathered structures in the high curvature regions can be
      separated by virtual rotation. RESULTS: The proposed methods were validated using
      two three-dimensional phantoms and 87 CT data sets. A study on the observation
      performance of the everted data showed that the reading times were (63% of time
      reduction for phantom A, 65% of time reduction for phantom B, and 77% of time
      reduction for CT data) less than those using virtual colonoscopy, while
      maintaining the sensibility. The incidence of improperly everted regions in the
      virtual eversion based on the outer surface centerline was 71% less than that
      based on the inner surface centerline. CONCLUSIONS: The virtual eversion based on
      the outer surface centerline is more accurate than the one based on the inner
      surface centerline whether the colon's inner surface is smooth or ragged. The
      time required for polyp detection using the virtual eversion is considerably less
      than that using the conventional virtual endoscopy. Virtual eversion and virtual
      rotation are promising methods for the rapid location of colonic polyps. Together
      with virtual colonoscopy and virtual flattening, virtual eversion and virtual
      rotation can be integrated to produce a powerful system for diagnosing colonic
      lesions.

PMID- 21089788
TI  - Iterative reconstruction of Fourier-rebinned PET data using sinogram blurring
      function estimated from point source scans.
AB  - PURPOSE: The accuracy of the system model that governs the transformation from
      the image space to the projection space in positron emission tomography (PET)
      greatly affects the quality of reconstructed images. For efficient computation in
      iterative reconstructions, the system model in PET can be factored into a product
      of geometric projection and sinogram blurring function. To further speed up
      reconstruction, fully 3D PET data can be rebinned into a stack of 2D sinograms
      and then be reconstructed using 2D iterative algorithms. The purpose of this work
      is to develop a method to estimate the sinogram blurring function to be used in
      reconstruction of Fourier-rebinned data. METHODS: In a previous work, the authors
      developed an approach to estimating the sinogram blurring function of nonrebinned
      PET data from experimental scans of point sources. In this study, the authors
      extend this method to the estimation of sinogram blurring function for Fourier
      rebinned PET data. A point source was scanned at a set of sampled positions in
      the microPET II scanner. The sinogram blurring function is considered to be
      separable between the transaxial and axial directions. A radially and angularly
      variant 2D blurring function is estimated from Fourier-rebinned point source
      scans to model the transaxial blurring with consideration of the detector block
      structure of the scanner; a space-variant 1D blurring kernel along the axial
      direction is estimated separately to model the correlation between neighboring
      planes due to detector intrinsic blurring and Fourier rebinning. The estimated
      sinogram blurring function is incorporated in a 2D maximum a posteriori (MAP)
      reconstruction algorithm for image reconstruction. RESULTS: Physical phantom
      experiments were performed on the microPET II scanner to validate the proposed
      method. The authors compared the proposed method to 2D MAP reconstruction without
      sinogram blurring model and 2D MAP reconstruction with a Monte Carlo based
      blurring model. The results show that the proposed method produces images with
      improved contrast and spatial resolution. The reconstruction time is unaffected
      by the new method since the blurring component takes a relatively negligible part
      of the overall reconstruction time. CONCLUSIONS: The proposed method can estimate
      sinogram blurring matrix for Fourier-rebinned PET data and can be used to improve
      contrast and spatial resolution of reconstructed images. The method can be
      applied to other human and animal scanners.

PMID- 21089790
TI  - A new fast and fully automated software based algorithm for extracting
      respiratory signal from raw PET data and its comparison to other methods.
AB  - PURPOSE: Respiratory gating in PET is an approach used to minimize the negative
      effects of respiratory motion on spatial resolution. It is based on an initial
      determination of a patient's respiratory movements during a scan, typically using
      hardware based systems. In recent years, several fully automated databased
      algorithms have been presented for extracting a respiratory signal directly from
      PET data, providing a very practical strategy for implementing gating in the
      clinic. In this work, a new method is presented for extracting a respiratory
      signal from raw PET sinogram data and compared to previously presented automated
      techniques. METHODS: The acquisition of respiratory signal from PET data in the
      newly proposed method is based on rebinning the sinogram data into smaller data
      structures and then analyzing the time activity behavior in the elements of these
      structures. From this analysis, a 1D respiratory trace is produced, analogous to
      a hardware derived respiratory trace. To assess the accuracy of this fully
      automated method, respiratory signal was extracted from a collection of 22
      clinical FDG-PET scans using this method, and compared to signal derived from
      several other software based methods as well as a signal derived from a hardware
      system. RESULTS: The method presented required approximately 9 min of processing
      time for each 10 min scan (using a single 2.67 GHz processor), which in theory
      can be accomplished while the scan is being acquired and therefore allowing a
      real-time respiratory signal acquisition. Using the mean correlation between the
      software based and hardware based respiratory traces, the optimal parameters were
      determined for the presented algorithm. The mean/median/range of correlations for
      the set of scans when using the optimal parameters was found to be 0.58/0.68/0.07
      0.86. The speed of this method was within the range of real-time while the
      accuracy surpassed the most accurate of the previously presented algorithms.
      CONCLUSIONS: PET data inherently contains information about patient motion;
      information that is not currently being utilized. We have shown that a
      respiratory signal can be extracted from raw PET data in potentially real-time
      and in a fully automated manner. This signal correlates well with hardware based
      signal for a large percentage of scans, and avoids the efforts and complications
      associated with hardware. The proposed method to extract a respiratory signal can
      be implemented on existing scanners and, if properly integrated, can be applied
      without changes to routine clinical procedures.

PMID- 21089791
TI  - Report on carcinogens.

PMID- 21089789
TI  - Measuring output factors of small fields formed by collimator jaws and multileaf
      collimator using plastic scintillation detectors.
AB  - PURPOSE: As the practice of using high-energy photon beams to create therapeutic
      radiation fields of subcentimeter dimensions (as in intensity-modulated
      radiotherapy or stereotactic radiosurgery) grows, so too does the need for
      accurate verification of beam output at these small fields in which standard
      practices of dose verification break down. This study investigates small-field
      output factors measured using a small plastic scintillation detector (PSD), as
      well as a 0.01 cm3 ionization chamber. Specifically, output factors were measured
      with both detectors using small fields that were defined by either the X-Y
      collimator jaws or the multileaf collimator (MLC). METHODS: A PSD of 0.5 mm
      diameter and 2 mm length was irradiated with 6 and 18 MV linac beams. The PSD was
      positioned vertically at a source-to-axis distance of 100 cm, at 10 cm depth in a
      water phantom, and irradiated with fields ranging in size from 0.5 x 0.5 to 10 x
      10 cm2. The field sizes were defined either by the collimator jaws alone or by a
      MLC alone. The MLC fields were constructed in two ways: with the closed leaves
      (i.e., those leaves that were not opened to define the square field) meeting at
      either the field center line or at a 4 cm offset from the center line.
      Scintillation light was recorded using a CCD camera and an estimation of error in
      the median-filtered signals was made using the bootstrapping technique.
      Measurements were made using a CC01 ionization chamber under conditions identical
      to those used for the PSD. RESULTS: Output factors measured by the PSD showed
      close agreement with those measured using the ionization chamber for field sizes
      of 2.0 x 2.0 cm2 and above. At smaller field sizes, the PSD obtained output
      factors as much as 15% higher than those found using the ionization chamber by
      0.6 x 0.6 cm2 jaw-defined fields. Output factors measured with no offset of the
      closed MLC leaves were as much as 20% higher than those measured using a 4 cm
      leaf offset. CONCLUSIONS: The authors' results suggest that PSDs provide a useful
      and possibly superior alternative to existing dosimetry systems for small fields,
      as they are inherently less susceptible to volume-averaging and perturbation
      effects than larger, air-filled ionization chambers. Therefore, PSDs may provide
      more accurate small-field output factor determination, regardless of the
      collimation mechanism.

PMID- 21089792
TI  - Acetaldehyde.

PMID- 21089793
TI  - 2-Acetylaminofluorene.

PMID- 21089794
TI  - Acrylamide.

PMID- 21089795
TI  - Acrylonitrile.

PMID- 21089796
TI  - Adriamycin (doxorubicin hydrochloride).

PMID- 21089797
TI  - Aflatoxins.

PMID- 21089798
TI  - Alcoholic beverage consumption.

PMID- 21089799
TI  - 2-Aminoanthraquinone.

PMID- 21089800
TI  - 4-Aminobiphenyl.

PMID- 21089801
TI  - 1-Amino-2,4-dibromoanthraquinone.

PMID- 21089802
TI  - 1-Amino-2-methylanthraquinone.

PMID- 21089803
TI  - o-Anisidine hydrochloride.

PMID- 21089804
TI  - Arsenic compounds, inorganic.

PMID- 21089805
TI  - Asbestos.

PMID- 21089806
TI  - Azacitidine.

PMID- 21089807
TI  - Azathioprine.

PMID- 21089808
TI  - Benzene.

PMID- 21089809
TI  - Benzidine.

PMID- 21089810
TI  - Dyes metabolized to benzidine (benzidine dye class).

PMID- 21089811
TI  - Benzotrichloride.

PMID- 21089812
TI  - Beryllium and beryllium compounds .

PMID- 21089813
TI  - Bromodichloromethane.

PMID- 21089814
TI  - 2,2-bis(Bromomethyl)-1,3-propanediol (technical grade).

PMID- 21089815
TI  - 1,3-Butadiene.

PMID- 21089816
TI  - 1,4-Butanediol dimethanesulfonate (Myleran).

PMID- 21089817
TI  - Butylated hydroxyanisole (BHA).

PMID- 21089819
TI  - Carbon tetrachloride.

PMID- 21089818
TI  - Cadmium and cadmium compounds.

PMID- 21089820
TI  - Ceramic fibers (respirable size).

PMID- 21089821
TI  - Chlorambucil.

PMID- 21089822
TI  - Chloramphenicol.

PMID- 21089823
TI  - Chlorendic acid.

PMID- 21089824
TI  - Chlorinated paraffins (C12, 60% chlorine).

PMID- 21089825
TI  - 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea.

PMID- 21089826
TI  - 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea.

PMID- 21089827
TI  - Chloroform.

PMID- 21089828
TI  - Bis(Chloromethyl) ether and technical-grade chloromethyl methyl ether.

PMID- 21089829
TI  - 3-Chloro-2-methylpropene.

PMID- 21089830
TI  - 4-Chloro-o-phenylenediamine.

PMID- 21089831
TI  - Chloroprene.

PMID- 21089832
TI  - p-Chloro-o-toluidine and p-chloro-o-toluidine hydrochloride.

PMID- 21089833
TI  - Chlorozotocin.

PMID- 21089834
TI  - Chromium hexavalent compounds.

PMID- 21089835
TI  - C.I. Basic Red 9 monohydrochloride.

PMID- 21089836
TI  - Cisplatin.

PMID- 21089837
TI  - Coal tars and coal tar pitches.

PMID- 21089838
TI  - Cobalt sulfate.

PMID- 21089839
TI  - Coke oven emissions.

PMID- 21089840
TI  - p-Cresidine.

PMID- 21089841
TI  - Cupferron.

PMID- 21089842
TI  - Cyclophosphamide.

PMID- 21089843
TI  - Cyclosporin A.

PMID- 21089844
TI  - Dacarbazine.

PMID- 21089845
TI  - Danthron (1,8-dihydroxyanthraquinone).

PMID- 21089846
TI  - 2,4-Diaminoanisole sulfate.

PMID- 21089847
TI  - 2,4-Diaminotoluene.

PMID- 21089848
TI  - Diazoaminobenzene.

PMID- 21089849
TI  - 1,2-Dibromo-3-chloropropane.

PMID- 21089850
TI  - 1,2-Dibromoethane (ethylene dibromide).

PMID- 21089851
TI  - 2,3-Dibromo-1-propanol.

PMID- 21089852
TI  - 1,4-Dichlorobenzene.

PMID- 21089853
TI  - 3,3'-Dichlorobenzidine and 3,3'-dichlorobenzidine dihydrochloride.

PMID- 21089854
TI  - Dichlorodiphenyltrichloroethane (DDT).

PMID- 21089855
TI  - 1,2-Dichloroethane (ethylene dichloride).

PMID- 21089856
TI  - Dichloromethane (methylene chloride).

PMID- 21089857
TI  - 1,3-Dichloropropene (technical grade).

PMID- 21089858
TI  - Diepoxybutane.

PMID- 21089859
TI  - Diesel exhaust particulates.

PMID- 21089860
TI  - Diethyl sulfate.

PMID- 21089861
TI  - Diethylstilbestrol.

PMID- 21089862
TI  - Diglycidyl resorcinol ether.

PMID- 21089863
TI  - 3,3'-Dimethoxybenzidine.

PMID- 21089864
TI  - Dyes metabolized to 3,3'-dimethoxybenzidine (3,3'-dimethoxybenzidine dye class).

PMID- 21089865
TI  - 4-Dimethylaminoazobenzene.

PMID- 21089866
TI  - 3,3'-Dimethylbenzidine.

PMID- 21089867
TI  - Dyes metabolized to 3,3'-dimethylbenzidine (3,3'-dimethylbenzidine dye class).

PMID- 21089868
TI  - Dimethylcarbamoyl chloride.

PMID- 21089869
TI  - Dimethyl sulfate.

PMID- 21089870
TI  - Dimethylvinyl chloride.

PMID- 21089871
TI  - Disperse Blue 1.

PMID- 21089872
TI  - Epichlorohydrin.

PMID- 21089873
TI  - Erionite.

PMID- 21089874
TI  - Estrogens, steroidal.

PMID- 21089875
TI  - Ethylene oxide.

PMID- 21089876
TI  - Ethylene thiourea.

PMID- 21089877
TI  - Di(2-ethylhexyl) phthalate.

PMID- 21089878
TI  - Ethyl methanesulfonate.

PMID- 21089879
TI  - Formaldehyde (gas).

PMID- 21089880
TI  - Furan.

PMID- 21089881
TI  - Glass wool (respirable size).

PMID- 21089882
TI  - Glycidol.

PMID- 21089883
TI  - Hepatitis B virus.

PMID- 21089884
TI  - Hepatitis C virus.

PMID- 21089885
TI  - Selected heterocyclic amines.

PMID- 21089886
TI  - Hexachlorobenzene.

PMID- 21089887
TI  - Hexachloroethane.

PMID- 21089888
TI  - Hexamethylphosphoramide.

PMID- 21089889
TI  - Human papillomaviruses: some genital-mucosal types.

PMID- 21089890
TI  - Hydrazine and hydrazine sulfate.

PMID- 21089891
TI  - Hydrazobenzene.

PMID- 21089892
TI  - X-radiation and gamma radiation.

PMID- 21089893
TI  - Neutrons.

PMID- 21089894
TI  - Radon.

PMID- 21089895
TI  - Thorium dioxide.

PMID- 21089896
TI  - Iron dextran complex.

PMID- 21089897
TI  - Isoprene.

PMID- 21089898
TI  - Kepone (chlordecone).

PMID- 21089899
TI  - Lindane and other hexachlorocyclohexane isomers.

PMID- 21089900
TI  - Melphalan.

PMID- 21089901
TI  - Methoxsalen with ultraviolet A therapy (PUVA).

PMID- 21089902
TI  - 2-Methylaziridine (propylenimine).

PMID- 21089903
TI  - 4,4'-Methylenebis(2-chloroaniline).

PMID- 21089904
TI  - 4,4'-Methylenebis(N,N-dimethyl)benzenamine.

PMID- 21089905
TI  - 4,4'-Methylenedianiline and its dihydrochloride salt.

PMID- 21089906
TI  - Methyleugenol.

PMID- 21089907
TI  - Methyl methanesulfonate.

PMID- 21089908
TI  - N-methyl-N'-nitro-N-nitrosoguanidine.

PMID- 21089909
TI  - Metronidazole.

PMID- 21089910
TI  - Mineral oils (untreated and mildly treated).

PMID- 21089911
TI  - Mirex.

PMID- 21089912
TI  - Mustard gas (bis[2-chloroethyl] sulfide).

PMID- 21089913
TI  - Naphthalene.

PMID- 21089914
TI  - 2-Naphthylamine.

PMID- 21089915
TI  - Nickel compounds and metallic nickel.

PMID- 21089916
TI  - Nitrilotriacetic acid.

PMID- 21089917
TI  - o-Nitroanisole.

PMID- 21089918
TI  - Nitroarenes (selected) 1,6-dinitropyrene.

PMID- 21089919
TI  - Nitroarenes (selected) 1,8-dinitropyrene.

PMID- 21089920
TI  - Nitroarenes (selected) 6-nitrochrysene.

PMID- 21089921
TI  - Nitroarenes (selected) 1-nitropyrene.

PMID- 21089922
TI  - Nitroarenes (selected) 4-nitropyrene.

PMID- 21089923
TI  - Nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether).

PMID- 21089924
TI  - Nitromethane.

PMID- 21089925
TI  - 2-Nitropropane.

PMID- 21089926
TI  - N-nitrosodi-n-butylamine.

PMID- 21089927
TI  - N-nitrosodiethanolamine.

PMID- 21089928
TI  - N-Nitrosodiethylamine.

PMID- 21089929
TI  - N-Nitrosodimethylamine.

PMID- 21089930
TI  - N-Nitrosodi-n-propylamine.

PMID- 21089932
TI  - 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone.

PMID- 21089931
TI  - N-nitroso-N-ethylurea.

PMID- 21089933
TI  - N-Nitroso-N-methylurea.

PMID- 21089934
TI  - N-Nitrosomethylvinylamine.

PMID- 21089935
TI  - N-Nitrosomorpholine.

PMID- 21089936
TI  - N-Nitrosonornicotine.

PMID- 21089937
TI  - N-Nitrosopyrrolidine.

PMID- 21089938
TI  - N-Nitrososarcosine.

PMID- 21089939
TI  - Ochratoxin A.

PMID- 21089940
TI  - 4,4'-Oxydianiline.

PMID- 21089941
TI  - Oxymetholone.

PMID- 21089942
TI  - Phenacetin and analgesic mixtures containing phenacetin.

PMID- 21089943
TI  - Phenazopyridine hydrochloride.

PMID- 21089944
TI  - Phenolphthalein.

PMID- 21089945
TI  - Phenoxybenzamine hydrochloride.

PMID- 21089946
TI  - Polybrominated biphenyls (PBBs).

PMID- 21089947
TI  - Polychlorinated biphenyls (PCBs).

PMID- 21089948
TI  - Polycyclic aromatic hydrocarbons, 15 listings.

PMID- 21089949
TI  - Procarbazine hydrochloride.

PMID- 21089950
TI  - Progesterone.

PMID- 21089951
TI  - 1,3-Propane sultone.

PMID- 21089952
TI  - Propylene oxide.

PMID- 21089953
TI  - Propylthiouracil.

PMID- 21089954
TI  - Reserpine.

PMID- 21089955
TI  - Safrole.

PMID- 21089956
TI  - Selenium sulfide.

PMID- 21089957
TI  - Silica, crystalline (respirable size).

PMID- 21089958
TI  - Soots.

PMID- 21089959
TI  - Streptozotocin.

PMID- 21089960
TI  - Styrene-7,8-oxide.

PMID- 21089961
TI  - Sulfallate.

PMID- 21089962
TI  - Tamoxifen.

PMID- 21089963
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); "dioxin".

PMID- 21089964
TI  - Tetrachloroethylene (perchloroethylene).

PMID- 21089965
TI  - Tetranitromethane.

PMID- 21089966
TI  - Thioacetamide.

PMID- 21089967
TI  - 4,4'-Thiodianiline.

PMID- 21089968
TI  - Thiotepa.

PMID- 21089969
TI  - Thiourea.

PMID- 21089970
TI  - Environmental tobacco smoke.

PMID- 21089971
TI  - Smokeless tobacco.

PMID- 21089972
TI  - Tobacco smoking.

PMID- 21089973
TI  - Toluene diisocyanates.

PMID- 21089974
TI  - o-Toluidine and o-toluidine hydrochloride.

PMID- 21089975
TI  - Toxaphene.

PMID- 21089976
TI  - Trichloroethylene.

PMID- 21089977
TI  - 2,4,6-Trichlorophenol.

PMID- 21089978
TI  - 1,2,3-Trichloropropane.

PMID- 21089979
TI  - Ultraviolet radiation related exposures.

PMID- 21089980
TI  - Urethane.

PMID- 21089981
TI  - Vinyl bromide.

PMID- 21089982
TI  - Vinyl chloride.

PMID- 21089983
TI  - 4-Vinyl-1-cyclohexene diepoxide.

PMID- 21089984
TI  - Vinyl fluoride.

PMID- 21089985
TI  - Wood dust.

PMID- 21089986
TI  - National Ambulatory Medical Care Survey: 2007 summary.
AB  - OBJECTIVES: This report describes ambulatory care visits made to physician
      offices in the United States. Statistics are presented on selected
      characteristics of the physician's practice, the patient, and the visit. METHODS:
      The data presented in this report were collected in the 2007 National Ambulatory
      Medical Care Survey (NAMCS), a national probability sample survey of visits to
      nonfederal office-based physicians in the United States. Sample data are weighted
      to produce annual national estimates of physician visits. RESULTS: During 2007,
      an estimated 994.3 million visits were made to physician offices in the United
      States, an overall rate of 335.6 visits per 100 persons. About one-third of
      office visits, 34.9 percent, were made to practices with all or partial
      electronic medical records systems, while 85.1 percent of the visits were made to
      practices with all or partial electronic submission of claims. From 1997 to 2007,
      the percentage of visits to physicians who were solo practitioners decreased 21
      percent. During the same period, visits to physicians who were part of a group
      practice with 6-10 physicians increased 46 percent. There were an estimated 106.5
      million injury- or poisoning-related office visits in 2007, representing 10.7
      percent of all visits. Medications were ordered, supplied, or administered at
      727.7 million office visits, accounting for 73.2 percent of all office visits. In
      2007, about 2.3 billion drugs were ordered, supplied, or administered, resulting
      in an average of 226.3 drug mentions per 100 visits.

PMID- 21089987
TI  - All careproviders need more opportunities to share their ethical concerns with
      others.
AB  - Attention to the ethical concerns of healthcare aides can provide important
      information about patients' needs to careproviders, improve the ethical
      environment of an institution, and benefit aides who suffer from bearing ethical
      concerns alone. All persons benefit from sharing their ethical concerns with
      others. Among other benefits, ethics consultation offers careproviders,
      caregivers, healthcare aides, patients, and patients' loved ones an opportunity
      to have their concerns heard. John Fletcher tried to follow every ethics
      consultation with a debriefing for all participants, including patients and
      family members, to increase the possibility for continued healing after the
      conclusion of the consultation, and there are good reasons to follow this
      practice.

PMID- 21089988
TI  - The rational choice model in family decision making at the end of life.
AB  - BACKGROUND: Most end-of-life decisions are made by family members. Current
      ethical guidelines for family decision making are based on a hierarchical model
      that emphasizes the patient's wishes over his or her best interests. Evidence
      suggests that the model poorly reflects the strategies and priorities of many
      families. METHODS: Researchers observed and recorded 26 decision-making meetings
      between hospital staff and family members. Semi-structured follow-up interviews
      were conducted. Transcriptions were analyzed using qualitative techniques.
      RESULTS: For both staff and families, consideration of a patient's best interests
      generally took priority over the patient's wishes. Staff generally introduced
      discussion of the patient's wishes for rhetorical purposes, such as persuasion.
      Competing moral frameworks, which de-emphasized the salience of patients'
      autonomy and "right to choose," played a role in family decision making.
      CONCLUSIONS: The priority given to the patients' wishes in the hierarchical model
      does not reflect the priorities of staff and families in making decisions about
      end-of-life care.

PMID- 21089989
TI  - "Broken covenant": healthcare aides' "experience of the ethical" in caring for
      dying seniors in a personal care home.
AB  - Canada's population is aging, and seniors constitute the fastest growing
      demographic in the nation. The chronic health conditions, limited social support,
      functional decline, and cognitive impairment experienced by seniors may
      necessitate admission to a personal care home (PCH) setting up until the time of
      their death. The ethical problems that arise in the care of dying patients are
      numerous and complicated. The care of dying seniors in PCHs, however, is largely
      provided by frontline workers such as healthcare aides (HCAs), who usually have
      little training in palliative care or ethics. Research examining the
      identification and resolution of ethical problems in care of the dying has been
      conducted from the perspectives of nurses and physicians in various clinical
      settings, but the voice of HCAs in PCHs is virtually absent from clinical ethics.
      Given that the inability to satisfactorily resolve ethical issues in clinical
      practice is associated with feelings of guilt, powerlessness, avoiding contact
      with patients, failing to provide good physical care, and increased staff
      turnover, an empirical examination of HCAs' experiences of ethically challenging
      situations is warranted. We conducted a phenomenological study to access the
      lived experience of HCAs (N = 12) working in proprietary and nonproprietary care
      homes as they encountered situations they deemed ethically challenging in
      providing end-of-life care to dying seniors. The findings reported here
      explicate: (1) the types of situations that are ethically problematic for HCAs;
      (2) the meanings they assign to these situations, and (3) the impact such
      situations have on the provision of end-of-life care.

PMID- 21089990
TI  - Characterizing the level of risk in pediatric research: an ethical examination of
      the federal regulations.
AB  - Federal regulations require that the level of risk posed by pediatric research be
      classified as "minimal," "greater than minimal," or "a minor increase over
      minimal" Interpretation of the meaning of the levels has produced a significant
      literature exploring the ethical basis for making these determinations. This
      article examines the ethical basis of a variety of approaches proposed in the
      literature for classifying pediatric research risk. These approaches strive to
      take into account how society decides which risks are routinely accepted for
      children outside of research. It is concluded that ways of classifying risk
      should compare research risks to normal risks for children without special
      disability and take into account the concerns of the research subject's
      community.

PMID- 21089991
TI  - Protection of children in research: beyond pediatric risk levels: the emergence
      of the research subject advocate.
AB  - The author describes the role of the research subject advocate (RSA), inaugurated
      in 2001, which adds a fourth level of protection for human research subjects.

PMID- 21089992
TI  - Infant heart transplantation after cardiac death: ethical and legal problems.
AB  - The donation of organs after cardiac death in infants is not morally justified
      and should not be continued.

PMID- 21089993
TI  - Dying but not killing: donation after cardiac death donors and the recovery of
      vital organs.
AB  - Michael Potts, Paul A. Byrne, and David W. Evans are critical of donation after
      cardiac death (DCD). Contrary to the authors' assertion that the removal of vital
      organs is the proximate cause of death, the eventual fulfillment of the
      neurological criteria of death is solely dependant on the rate of brain cell
      death in the absence of circulation. Consistent with the "dead donor rule," DCD
      is not the cause of death.There are also procedural mechanisms to address the
      potential conflicts of interest that concern the authors. Rather than being
      prohibited, DCD may be an ethically justifiable exception to the rule that organ
      donors must be dead prior to organ recovery.

PMID- 21089994
TI  - Building esprit de corps: learning to better navigate between "my" patient and
      "our" patient.
AB  - Excellence in the care of hospital patients, particularly those in an intensive
      care unit, reflects esprit de corps among the care team. Esprit de corps depends
      on a delicate balance; each clinician must preserve a sense of personal
      responsibility for "my" patient and yet participate in the collaborative work
      essential to the care of "our" patient. A harmful imbalance occurs when a
      physician demands total control of the decision-making process, especially
      concerning end-of-life treatment options. Although emotional factors may push a
      physician to claim decision-making exclusivity, compounded by a legal framework
      that overemphasizes individual responsibility, esprit de corps can be preserved
      through timely communication among clinicians and a recognition that optimal care
      for "my" patient requires effective team practice.

PMID- 21089995
TI  - Esprit de corps: the possibility for the best care a hospital can provide.
AB  - What is best for the hospitalized patient? How do we increase the prospects that
      a patient will receive the best care a hospital can provide, and how is this
      accomplished? It has been argued that what is best for the patient is to be in
      the care of highly functioning collaborative teams, teams with certain unique
      qualities, teams that have esprit de corps. But how do we get there? In
      furtherance of this discussion, the author, in a Quintilian-like spirit,
      deliberates about "necessity" and "possibility" in what is best for the
      hospitalized patient and the challenges these teams must navigate:
      responsibility, accountability, team relationships, leadership, moral distress,
      dissent, and personal and professional risk.

PMID- 21089996
TI  - Legal briefing: organ donation and allocation.
AB  - This issue's "Legal Briefing" column covers legal developments pertaining to
      organ donation and allocation. This topic has been the subject of recent articles
      in JCE. Organ donation and allocation have also recently been the subjects of
      significant public policy attention. In the past several months, legislatures and
      regulatory agencies across the United States and across the world have changed,
      or considered changing, the methods for procuring and distributing human organs
      for transplantation. Currently, in the U.S., more than 100,000 persons are
      waiting for organ transplantation. In China, more than 1.5 million people are
      waiting. Given the chronic shortage of available organs (especially kidneys and
      livers) relative to demand, the primary focus of most legal developments has been
      on increasing the rate of donation. These and related developments are usefully
      divided into the following 12 topical categories: 1. Revised Uniform Anatomical
      Gift Act. 2. Presumed Consent and Opt-Out. 3. Mandated Choice. 4. Donation after
      Cardiac Death. 5. Payment and Compensation. 6. Donation by Prisoners. 7. Donor
      Registries. 8. Public Education. 9. Other Procurement Initiatives. 10. Lawsuits
      and Liability. 11. Trafficking and Tourism. 12. Allocation and Distribution.

PMID- 21089997
TI  - The ambiguous effects of tort law on bioethics: the case of doctor-patient
      communication.
AB  - Tort law is an important tool in enforcing a minimal level of good behavior. But
      what is appropriate for law is not necessarily appropriate for ethics or for
      norms of professional practice.

PMID- 21089998
TI  - Business interests versus informed consent.

PMID- 21089999
TI  - Prevalence of epidermal conditions in California coastal bottlenose dolphins
      (Tursiops truncatus) in Monterey Bay.
AB  - The prevalence of epidermal conditions in a small population of coastal
      bottlenose dolphins (Tursiops truncatus) in Monterey Bay was evaluated between
      2006 and 2008. Five different skin condition categories were considered,
      including Pox-Like Lesions, Discoloration, Orange Film, Polygon Lesions, and
      Miscellaneous Markings. Of 147 adults and 42 calves photographically examined, at
      least 90 and 71%, respectively, were affected by at least one or multiple
      conditions. Pox-Like Lesions were the most prevalent, affecting 80% of the
      population, including adults and calves. This condition warrants the most urgent
      investigation being possibly indicative of the widespread presence of poxvirus or
      a similar pathogen in the population. In view of the high number of individuals
      affected, standard monitoring of the health status of Monterey Bay bottlenose
      dolphins is considered imperative. Discoloration was strongly associated with Pox
      Like lesions. Orange Films were likely an epifaunal infestation caused by
      diatoms, which have been documented in other cetacean species. Polygon Lesions, a
      newly described category, could be the result of infestation by barnacles of the
      genus Cryptolepas. Miscellaneous Markings were variable in appearance and may not
      have the same causative factor. Although none of the proposed etiologies can be
      confirmed without appropriate clinical tests, recognizing common visible
      characteristics of the conditions could aid in preliminary comparisons across
      populations and individuals.

PMID- 21090000
TI  - Patagonian fjord ecosystems in southern Chile as a highly vulnerable region:
      problems and needs.
AB  - Southern Chile encompasses one of the most extensive fjord regions of the world,
      the Patagonia, currently exposed to natural and anthropogenic perturbations.
      These fjord ecosystems provide important services to humans, which have not been
      adequately measured and valued. As a consequence, ecosystem services are commonly
      ignored in public policy design and in the evaluation of development projects.
      Here we tackle questions that are highly relevant for the nation's development,
      namely (1) understanding fjord functioning, and (2) developing management
      strategies based on ecosystem services, in order to secure simultaneous and
      adequate use of these ecosystems which area influenced by ecological (e.g.,
      biogeochemical) and productive (e.g., aquaculture, fisheries) processes. We also
      seek to strengthen the analysis of fjord ecosystem value from the economical
      (including coastal zoning), socio-cultural, institutional, and governmental
      points of view. In addition, the investigation of current and future effects of
      climate change on this large region offers a unique opportunity to understand the
      social and economic consequences of a global phenomenon at local to regional
      scales. Biogeochemical and socio-economic models will be used to simulate future
      scenarios under a gamut of management options.

PMID- 21090001
TI  - Urban water resources quota management: the core strategy for water demand
      management in China.
AB  - Since China has the largest population in the world, the available water
      resources per capita in China are very limited. With the rapid economic
      development that is currently occurring, the shortage of water resources at the
      national level has become extremely critical. How to solve the problems due to
      water scarcity and water pollution has received increasing attention from the
      Chinese government and various communities. In order to provide a sustainable
      development environment for 1.6 billion people in the future, the whole country
      has started to reform urban water resources management systems in terms of
      related policies, regulations, methodologies, and technologies focusing on
      improving the efficiency and effectiveness in water use. Urban water quota
      management has now become a core strategy in developing a water resources
      governance model for water demand management aiming at establishing a water
      saving society. This paper introduces the main stages and the processes of
      implementing water quota management in China, analyzes the basic principles, and
      expounds the elements, information foundation, core module and operational model
      of the urban water quota management system. It has been demonstrated that urban
      water quota management has made some remarkable contribution not only in
      transforming the pattern of water mode and strengthening water management
      enforcement but also in integrating various management methods in saving water
      and preventing pollution.

PMID- 21090002
TI  - Assessment of blue mussel Mytilus edulis fisheries and waterbird shellfish
      predator management in the Danish Wadden Sea.
AB  - We assessed the blue mussel Mytilus edulis fishery management scheme introduced
      in 1994 in the Danish Wadden Sea that regulate fishing vessels, fishery quota,
      set-aside for mussel-eating birds and established zones closed to mussel fishery.
      The results showed (i) a reduction in the blue mussel biomass and mussel bed
      areas in zones closed to fishery, (ii) decrease in eiders Somateria mollissima
      numbers and increase or stable numbers for oystercatcher Haematopus ostralegus
      and herring gull Larus argentatus and (iii) that energy estimations based on
      ecological food requirements for the mussel-eating birds should be at least three
      times larger, than the amount set-aside in the mussel management scheme. It is
      concluded that the mussel management scheme had been unable to stabilize or
      increase the blue mussel stocks and to secure stable or increasing numbers for
      all target bird species. Thus, it is recommended to revise the present blue
      mussel management scheme in the Danish Wadden Sea, to continue and improve mussel
      stock and bird surveys, and to consider novel studies of the mussel-eating birds'
      energetics for improved set-aside estimates and future assessments.

PMID- 21090003
TI  - Indications of recovery from hypoxia in the inner Stockholm archipelago.
AB  - Improved benthic conditions compared to the 1990s were found during benthic
      investigations, including sediment and benthic macrofauna in the inner Stockholm
      archipelago during 2008. In the 1990s, these areas were dominated by black and
      laminated surface sediments and very sparse fauna. A clear relationship was found
      when comparing sediment status with the benthic macrofauna. Reduced surface
      sediment and impoverished macroinvertebrate community was only found at one
      sampling station representing an enclosed part of the inner archipelago, whereas
      the other seven stations, with depths ranging from 20 to 50 m, had oxidized
      surface sediments and considerable biomasses of benthic macrofauna (6-65 g m(-2))
      dominated by the invading polychaete Marenzelleria neglecta. An extrapolation of
      the results shows that, within the investigated area, the coverage of reduced
      surface sediments had decreased from approximately 17% in the late 1990s to 4% in
      2008.

PMID- 21090004
TI  - Recent changes in body size of the Eurasian otter Lutra lutra in Sweden.
AB  - We studied geographical and temporal body size trends among 169 adult museum
      specimens of the Eurasian otter (Lutra lutra) collected in Sweden between 1962
      and 2008, whose sex, year of collection, and locality were known. Skull size and
      body mass increased significantly in relation to the year of collection, and
      skull size (but not body mass) was significantly and negatively related to
      latitude, contrasting Bergmann's rule and the trend found for Norwegian otters.
      Latitudinal differences in body size between the two countries may be due to
      differences in food availability. The temporal increase in body size among
      Swedish otters resembled that observed for Norway otters, though Swedish otters
      are smaller with respect to their Norwegian counterparts. Latitude and year
      represent a combination of environmental factors, including ambient temperature
      in the year of collection as well as the number of days of ice coverage. We
      replaced the above factors with mean annual temperature or the number of days of
      ice coverage, and found that each of these factors explains a similar proportion
      of the variation in body size as did latitude and year. We hypothesize that this
      temporal increase in body size is related to a combination of factors, including
      reduced energy expenditure resulting from increasing ambient temperature, and
      increased food availability from longer ice-free periods.

PMID- 21090005
TI  - Estimation of nitrogen and phosphorus in effluent from the striped catfish
      farming sector in the Mekong Delta, Vietnam.
AB  - In this study an attempt is made to estimate nitrogen and phosphorus discharged
      to the environment from the striped catfish (Pangasianodon hypophthalmus) farming
      sector in the Mekong Delta (8 degrees 33'-10 degrees 55' N, 104 degrees 30'-106
      degrees 50' E), South Vietnam. The sector accounted for 687,000 t production in
      2007 and 1,094,879 t in 2008, with over 95% of the produce destined for export to
      over 100 countries. Commercial and farm-made feeds are used in catfish farming,
      currently the former being more predominant. Nitrogen discharge levels were
      similar for commercial feeds (median 46.0 kg/t fish) and farm-made feeds (median
      46.8 kg/t fish); whilst, phosphorus discharge levels for commercial feeds (median
      14.4 kg/t fish) were considerably lower than for farm-made feeds (median 18.4
      kg/t fish). Based on the median nutrient discharge levels for commercial feeds,
      striped catfish production in the Mekong Delta discharged 31,602 t N and 9,893 t
      P, and 50,364 t N and 15,766 t P in 2007 and 2008, respectively. However, the
      amount of nutrients returned directly to the Mekong River may be substantially
      less than this as a significant proportion of the water used for catfish farming
      as well as the sludge is diverted to other agricultural farming systems. Striped
      catfish farming in the Mekong Delta compared favourably with other cultured
      species, irrespective of the type of feed used, when the total amounts of N and P
      discharged in the production of a tonne of production was estimated.

PMID- 21090006
TI  - Charging for nature: marine park fees and management from a user perspective.
AB  - User fees can contribute to the financial sustainability of marine protected
      areas (MPAs), yet they must be acceptable to users. We explore changes in the fee
      system and management of Bonaire National Marine Park (BNMP) from the perspective
      of users. Responses from 393 tourists indicated that 90% were satisfied with park
      conditions and considered current user fees reasonable. However, only 47% of
      divers and 40% of non-divers were prepared to pay more. Diver willingness-to-pay
      (WTP) appears to have decreased since 1991, but this difference could be due in
      part to methodological differences between studies. Although current fees are
      close to diver maximum stated WTP, revenues could potentially be increased by
      improving the current fee system in ways that users deem acceptable. This
      potential surplus highlights the value of understanding user perceptions toward
      MPA fees and management.

PMID- 21090007
TI  - Reviewing the history of natural sciences research on the Bothnian Sea, 1975
      2008.

PMID- 21090008
TI  - New perspectives on marine biodiversity.

PMID- 21090009
TI  - National survey on identifying vulnerable workers and availability of
      occupational health services in the Republic of Macedonia.
AB  - OBJECTIVE: In order to identify vulnerable groups and high risk sectors which are
      at greater need of basic occupational health services, we performed a
      questionnaire-based study including, as key informants, different stakeholders
      and key players in the process of improving health and safety at work. METHODS:
      The Institute of Occupational Health of Macedonia developed an specially designed
      questionnaire in collaboration with the WHO Regional Office for Europe.
      Vulnerable groups/sectors include: unemployed, female workers, workers aged under
      18 years, workers aged over 55 years and workers in the informal sector,
      construction industry, textile industry, agriculture, and the health care
      workers. The Likert scale method was used to evaluate most of the questions in
      the questionnaire, and the study subjects were instructed to give their
      professional opinion in completing the questionnaire. RESULTS: All examined
      groups/sectors were judged to have high risk for occupationally related health
      problems by over 70% of the responders. Aging workers and workers in agriculture
      and in the construction industry were judged to have the highest risk for such
      problems, as well as low health status. All examined groups/sectors were judged
      to have good availability of primary health care services, while agriculture,
      unemployed, the informal sector and young workers were judged as having poor
      availability of occupational health services. CONCLUSION: The provision of Basic
      Occupational Health Services (BOHS) incorporated in the framework of primary
      health care via the public health approach was judged as a good conceptfor
      Macedonia.

PMID- 21090011
TI  - HIEs: the $500M gamble.

PMID- 21090010
TI  - Renewing the call for a ban on asbestos.

PMID- 21090012
TI  - Is a picture worth a thousand interfaces?

PMID- 21090013
TI  - Ascending the HIMSS ladder.

PMID- 21090014
TI  - Taking the measure of EHRs.

PMID- 21090015
TI  - Melting pot.

PMID- 21090016
TI  - Specialty expert. Interview by Elizabeth Gardner.

PMID- 21090017
TI  - The Kaiser Permanente performance improvement system series.

PMID- 21090018
TI  - Kaiser Permanente's performance improvement system, Part 1: From benchmarking to
      executing on strategic priorities.
AB  - BACKGROUND: By 2004, senior leaders at Kaiser Permanente, the largest not-for
      profit health plan in the United States, recognizing variations across service
      areas in quality, safety, service, and efficiency, began developing a performance
      improvement (PI) system to realizing best-in-class quality performance across all
      35 medical centers. MEASURING SYSTEMWIDE PERFORMANCE: In 2005, a Web-based data
      dashboard, "Big Q," which tracks the performance of each medical center and
      service area against external benchmarks and internal goals, was created.
      PLANNING FOR PI AND BENCHMARKING PERFORMANCE: In 2006, Kaiser Permanente national
      and regional continued planning the PI system, and in 2007, quality, medical
      group, operations, and information technology leaders benchmarked five high
      performing organizations to identify capabilities required to achieve consistent
      best-in-class organizational performance. THE PI SYSTEM: The PI system addresses
      the six capabilities: leadership priority setting, a systems approach to
      improvement, measurement capability, a learning organization, improvement
      capacity, and a culture of improvement. PI "deep experts" (mentors) consult with
      national, regional, and local leaders, and more than 500 improvement advisors are
      trained to manage portfolios of 90-120 day improvement initiatives at medical
      centers. IMPACT: Between the second quarter of 2008 and the first quarter of
      2009, performance across all Kaiser Permanente medical centers improved on the
      Big Q metrics. CONCLUSIONS: The lessons learned in implementing and sustaining PI
      as it becomes fully integrated into all levels of Kaiser Permanente can be
      generalized to other health care systems, hospitals, and other health care
      organizations.

PMID- 21090019
TI  - Linking emergency preparedness and health care worker vaccination against
      influenza: a novel approach.
AB  - BACKGROUND: Health care workers (HCWs) can acquire and transmit influenza to
      their patients and coworkers, even while asymptomatic. The U.S. Healthy People
      2010 initiative set a national goal of 60% coverage for HCW influenza vaccination
      by 2010. Yet vaccination rates remain low. In the 2008-2009 influenza season,
      Flushing Hospital Medical Center (FHMC; New York) adopted a "push/pull" point-of
      dispensing (POD) vaccination model that was derived from emergency preparedness
      planning for mass vaccination and/or prophylaxis to respond to an infectious
      disease outbreak, whether occurring naturally or due to bioterrorism. LAUNCH OF
      THE HCW VACCINATION PROGRAM: In mid-September 2008, a two-week HCW vaccination
      program was launched using a sequential POD approach. In Push POD, teams assigned
      to specific patient units educated all HCWs about influenza vaccination and
      offered on-site vaccination; vaccinated HCWs received a 2009 identification (ID)
      validation sticker. In Pull POD, HCWs could enter the hospital only through one
      entrance; all other employee entrances were "locked down." A 2009 ID validation
      sticker was required for entry and to punch in for duty. Employees without the
      new validation sticker were directed to a nearby vaccination team. After the
      Push/Pull POD was completed, the employee vaccination drive at FHMC was continued
      for the remainder of the influenza season by the Employee Health Service.
      RESULTS: Using this model, in two days 72% of the employees were reached, with
      54% of those reached accepting vaccination. CONCLUSIONS: This model provides a
      novel approach for institutions to improve their HCW influenza vaccination rates
      within a limited period through exercising emergency preparedness plans for
      infectious disease outbreaks.

PMID- 21090020
TI  - Making inpatient medication reconciliation patient centered, clinically relevant,
      and implementable: a consensus statement on key principles and necessary first
      steps.
AB  - This white paper identifies potential solutions to help ensure the utility and
      sustainability of this critical patient safety issue.

PMID- 21090021
TI  - Rapid response systems: from implementation to evidence base.
AB  - This conference report presents highlights from the Sixth International
      Conference on Rapid Response Systems (RRSs) and Medical Emergency Teams.

PMID- 21090022
TI  - Using checklists to help ensure accountability in care.

PMID- 21090023
TI  - Executive/Senior Leader Checklist to improve culture and reduce central line
      associated bloodstream infections.

PMID- 21090024
TI  - Hospital Board Checklist to improve culture and reduce central line-associated
      bloodstream infections.

PMID- 21090025
TI  - Diligence before speedy execution.

PMID- 21090026
TI  - Staff comments were the last straw.

PMID- 21090027
TI  - Te sport of healing. Team physicians share a passion for helping players.

PMID- 21090028
TI  - Family Youth Assistance Network: helping families help their children with mental
      health diagnoses in Arkansas.

PMID- 21090029
TI  - An unusual cause of upper GI bleeding: gastric antral vascular ectasia.
AB  - Gastric antral vascular ectasia (GAVE) is characterized by red patches or spots
      in either a diffuse or linear array in the antrum of the stomach. This syndrome
      is commonly referred to as watermelon stomach because of its typical endoscopic
      appearance. Patients with GAVE frequently have occult bleeding requiring
      continual transfusions. It is important to distinguish the differences while
      treating GAVE in cirrhotics and portal hypertensive gastropathy (PHG) since the
      treatment options are vastly different.

PMID- 21090030
TI  - Sports concussion in the child and adolescent athlete.
AB  - Sports concussions are common among children and adolescents, and recent evidence
      suggests that concussions are more serious injuries than previously thought.
      Young athletes appear to recover from concussion more slowly than older athletes.
      Recovery is prolonged if these athletes return to play or school prematurely, and
      reinjury increases their risk of more serious sequelae. These newer data on
      concussions have raised our appreciation of this injury and have informed the
      development of more conservative treatment guidelines for the child and
      adolescent athlete. The purpose of this JAMS article is to review the new
      evidence and the most recent management guidelines regarding sports concussion in
      the young athlete.

PMID- 21090031
TI  - Community partnerships.
AB  - Hospitals and other organizations can tackle multifaceted wellness problems in
      homes and neighborhoods.

PMID- 21090032
TI  - Access.
AB  - As reform increases insurance coverage, hospitals need to focus on caring for
      patients at the right place and the right time.

PMID- 21090033
TI  - Bundled payments and the board's role.

PMID- 21090034
TI  - Smart leadership.
AB  - ACOs, bundled payments and other aspects of reform will require new skills in the
      C-suite.

PMID- 21090035
TI  - Survival strategies for community hospitals.
AB  - Stand-alone hospitals have several options when forming partnerships with larger
      institutions or systems.

PMID- 21090036
TI  - Creating a culture of ownership.
AB  - A struggling hospital re-examines its values and turns employee and patint
      satisfaction around.

PMID- 21090037
TI  - Flip the switch.
AB  - Preparing for reform puts leaders in a state of strategic schizophrenia.

PMID- 21090038
TI  - 10 indicators of excellent nursing care.
AB  - Key indicators can keep trustees up to date on their organization's quality of
      nursing care.

PMID- 21090039
TI  - Accountability at the top.
AB  - When trustees pushed for better hand hygiene, compliance rates soared.

PMID- 21090040
TI  - Some thoughts as we face challenging times.

PMID- 21090041
TI  - Article touting cone beam CT as new "standard of care" false and misleading.

PMID- 21090042
TI  - Electronic health records--I'm from the government and I'm here to help.

PMID- 21090043
TI  - Diagnostic discussion. Metastatic malignancy.

PMID- 21090045
TI  - Undetected microscopic pulp exposures in deep class II cavities.
AB  - Exposure of the pulp may act as a great insult during preparations, so this study
      investigated the probability of clinically undiagnosed pulp microexposures. The
      axial wall of 30 deep class II preparations in human premolars was searched for
      any microexposure after extraction. Seven teeth (23.7 percent) showed some kind
      of exposure. It is concluded that approximately one-fifth of class II
      preparations with the remaining dental thickness (RDT) less than 0.5 mm may have
      a pulpal microexposure.

PMID- 21090044
TI  - A holistic approach to a rare pathology.
AB  - A case of cystic hygroma (CH), a congenital lymph-filled multicystic hamartoma of
      the neck, with a holistic approach to patient management is presented. The stigma
      of the CH imposed by attending physicians, dentists, parents, teachers and peers
      affected the psychological development of this patient since her diagnosis in
      childhood. Although surgery relieves the threat of airway obstruction and may
      improve the esthetic appearance of the CH, the patient may be isolated and
      traumatized by the ignorance and superstitions of the individuals she encounters
      on a daily basis.

PMID- 21090046
TI  - Effects of analgesics on pre- and post-separator pain.

PMID- 21090047
TI  - Trigeminal neuralgia and radiofrequency.
AB  - Trigeminal neuralgia (TN) is a painful neurological disorder often mistaken for
      pain of dental origin by the patient and dentist. Dentists should be acquainted
      with TN to differentiate it from orofacial pain and prevent unnecessary tooth
      extraction. TN pain alleviating modalities are numerous, yet not uniformly
      effective. Radiofrequency, known for 25 years, is a minimally-invasive outpatient
      procedure used for TN when drugs are ineffective. The authors evaluate
      radiofrequency in trigeminal neuralgia patients referred from the dental office.

PMID- 21090048
TI  - Pain medications: what you need to know.

PMID- 21090049
TI  - Hepcidin: the link to understanding iron regulation.

PMID- 21090050
TI  - Immunology for detection of early-stage lung cancer.

PMID- 21090051
TI  - Collaborative medicine: weaving the microbiology laboratory into clinical
      practice.
AB  - The case presentation of K kingae osteoarthritis used here illustrates
      technological and procedural advances in microbiological diagnostics and
      communication. These activities are active in the sense that molecular
      developments are driving rapid diagnoses and that rapidly communicated results
      have the potential to drive better decision making and care. The hypothesis that
      a newer, less passive microbiology ("interventional microbiology") can improve
      care and reduce costs deserves testing in several institutions. If confirmed,
      rapid implementation of diagnostic pathways into standard practice, point-of-care
      molecular diagnostics, enhancement of traditional culture methods, and effective
      communication in emergency departments and hospitals are warranted and should be
      a focus for quality improvement.

PMID- 21090053
TI  - Sick-leave use or abuse?

PMID- 21090052
TI  - Where the heroes are: challenges and triumphs of war-zone labs. Interview by
      Karen Lynn.

PMID- 21090054
TI  - Labs get a PECOS reprieve.

PMID- 21090056
TI  - Coag tests get tweaked.

PMID- 21090055
TI  - Unexpected laboratory diagnosis: Acquired dysfibrinogenemia in a bleeding patient
      with liver disease.

PMID- 21090057
TI  - Tracking infectious diseases.

PMID- 21090058
TI  - ASCP opposes CMS on pod labs, signature requirement.

PMID- 21090059
TI  - Esposito leads Phadia's allergy-testing team.

PMID- 21090060
TI  - The importance of celebrating the excellence of peers.

PMID- 21090061
TI  - Balancing the boat: enabling an ocean of possibilities.
AB  - Working in partnership, occupational therapists help clients to "balance their
      boat" and engage in meaningful occupations as clients journey through life. Life
      balance requires prioritization between time spent at work and other life
      experiences. Leisure time provides opportunities to rest, re-energize and enjoy
      activities of one's choosing, and is vitally important to an individual's
      physical and mental health. As occupational therapists, we need to appreciate how
      valuable and meaningful these activities are. In particular, it is essential that
      we optimize balance between the "must do" activities that are often prioritized
      in our interventions, with the "would like to do" leisure activities that promote
      well-being and social engagement. Asking our clients about the leisure activities
      in which they would most like to participate promotes choice and a sense of
      control. Focusing on modifiable personal and environmental factors enables
      occupational therapists to address barriers to participation in leisure
      activities. Occupational therapists have the knowledge and skills to work with
      individuals, organizations and communities to advocate for policy and practice
      changes that will optimize participation for individuals with functional
      challenges.

PMID- 21090062
TI  - The experience of participation in everyday occupations for adults with obesity.
AB  - BACKGROUND: Participation in occupations of everyday life, such as self-care,
      work, and leisure, contribute to health and well-being. Obesity has been shown to
      influence health-related quality of life, but it is unclear how obesity
      influences participation in specific occupations. PURPOSE: To describe the lived
      experience of adults with class III obesity and the associated impact on
      participation in occupations of daily living. METHODS: Ten adults enrolled in an
      obesity treatment program were interviewed. Data were interpreted using
      descriptive phenomenological methods. FINDINGS: Participants underscored the
      tensions, barriers, and coping strategies across and within specific occupations.
      Although participation across occupations of daily living was described, the
      quality and diversity of occupations was influenced by real and perceived
      barriers within the environment. IMPLICATIONS: Participation in daily occupations
      is limited for persons with class III obesity. Intervention approaches should
      address health-related concerns and consider environmental adaptations that
      facilitate meaningful engagement in everyday life.

PMID- 21090063
TI  - Measures of knowledge and skills for evidence-based practice: a systematic
      review.
AB  - BACKGROUND: Lack of knowledge and skills in seeking, evaluating, and applying
      evidence are barriers to evidence-based practice (EBP). The measurement of these
      constructs can inform educational initiatives aimed at reducing EBP barriers.
      PURPOSE: The purpose of this systematic review is to provide a critical appraisal
      of the rehabilitation literature describing quantitative measures of EBP
      knowledge and skills. METHODS: Measures used with occupational therapists to
      evaluate EBP knowledge or skills were compiled from a search of the EMBASE,
      MEDLINE, CINAHL, EBM Reviews, and PSYCINFO databases. Measures were evaluated
      using adapted criteria from the CanChild Outcome Measures Rating Form. FINDINGS:
      Of the 15 measures identified, three met criteria as being adequate for the
      measurement of EBP knowledge and skills. IMPLICATIONS: Further measure
      development needs to address limitations of existing measures. Research to
      evaluate the psychometric properties of existing or novel measures of knowledge
      and skills related to EBP may improve their utility.

PMID- 21090064
TI  - Holding on to normalcy and overshadowed needs: family caregiving at end of life.
AB  - BACKGROUND: Caregivers in end-of-life care are at risk for health deterioration
      and decreased quality of life because of the many stressing factors involved in
      the caregiving role. PURPOSE: The purpose of this analysis is to come to
      understand the nature of occupation as experienced by family caregivers of dying
      patients at a residential hospice. METHODS: Data from hospice residents, their
      family members, and the hospice staff was collected over a period of six months
      via participant observation, interviews, and document review. FINDINGS: The
      themes "holding on to normalcy" and "overshadowed needs of caregivers" describe
      the complex and uncertain nature of family caregivers' occupation. IMPLICATIONS:
      Occupations of family caregivers reflected experiences of doing, being,
      belonging, and becoming. By looking through the lens of the caregiver, the
      findings of this study will help occupational therapists address the unique needs
      of the caregiver in end-of-life care.

PMID- 21090065
TI  - Advocacy in occupational therapy: exploring clinicians' reasons and experiences
      of advocacy.
AB  - BACKGROUND: Occupational therapy literature encourages therapists to advocate,
      yet any member of the team could advocate with/for people with disabilities.
      There is a need to determine why occupational therapists provide these services
      and how they learn to advocate. PURPOSE: The objective of this article is to
      understand the meaning of advocacy for occupational therapists by exploring their
      reasons for advocating. METHODS: Interpretive phenomenology and the social model
      of disability were used to interview 13 occupational therapists about their
      advocacy experiences. Data analysis was completed using a Gadamerian-based
      approach. FINDINGS: Occupational therapists advocate for a number of reasons;
      some relate to themselves, some relate to clients, and others relate to both.
      Learning about advocacy may be understood as taking place on a continuum of time.
      IMPLICATIONS: The occupational therapist's unique reason for advocating is to
      facilitate the client's occupational performance. A new definition of advocacy is
      presented based on study findings.

PMID- 21090066
TI  - Information used by an expert paediatric occupational therapist when making
      clinical decisions.
AB  - BACKGROUND: Occupational therapists use a range of types and sources of
      information when making clinical decisions. It is unclear how this information is
      integrated. PURPOSE: This paper describes an exploratory qualitative case study
      that identified the types and sources of information accessed by one experienced
      paediatric therapist and how this information was combined and prioritised when
      making clinical decisions. METHODS: . Data were collected using observations of
      therapy sessions, key informant interviews, and semi-structured interviews. Data
      were analysed thematically. FINDINGS: To inform clinical decisions, the
      participant prioritised information about each child in his or her context when
      making decisions. Other types of information from text books and journals,
      professional development activities and professional and personal experience,
      expanded her unique body of knowledge over time. IMPLICATIONS: Re
      conceptualisation of how information use supports clinical decision making and
      expands a therapist's unique body of knowledge over time can support client
      centred practice in occupational therapy.

PMID- 21090067
TI  - [Medicine and natural science--time for a change in paradigm].
AB  - Whereas in the 18th century medical science was influenced by both religion and
      the humanities, this changed around the middle of the 19th century as applied
      science accompanied a rapid development in medicine, especially in the fields of
      physiology and pathology. Currently the principles of biology, chemistry, and
      physics form the basis of scientifically-based medicine. This becomes even more
      evident when looking at the distribution of Nobel laureates for medicine and
      physiology in the first decade of the new millennium, namely 18 natural
      scientists compared with only 8 medical practitioners (see www.bnld.eu). In
      Germany, cooperation between medical practitioners and natural scientists is
      often hindered by legislation as well as professional claims. Whereas some
      procedures are restricted to medical practitioners, others, such as diagnostic
      testing, can be delegated to and performed by natural scientists, although here
      legal confirmation may be lacking in some cases, for example in genetics. Such
      discrimination often hinders potential cooperation and can no longer be seen as
      up to date. Whereas evidence based medicine forms the basis of individual
      treatment for patients, the introduction of disease management programmes by
      hospital administrators nullifies any positive effects of evidence-based medicine
      and reduces the patient to a cost-factor statistic. The aim of present government
      policy is a cost-effective treatment of diseases, often at the cost of the
      patient. Medicine is changing from an empirically-based therapy to a
      rationalised, molecular science. Parity between natural scientists and medical
      practitioners at all relevant levels is an indispensible prerequisite for a
      beneficial future healthcare programme. New, as well as existing professions for
      natural scientists in healthcare must be defined clearly and must have a legal
      basis, the point of view of the bnld (Berufsvereinigung der Naturwissenschaftler
      in der Labordiagnostik) for many years.

PMID- 21090068
TI  - [The neonatology network].

PMID- 21090069
TI  - [The Outpatient Health Care Package for the very premature infant: application of
      the program to follow-up services for the Neonatal Intensive Care, Pediatrics
      Department, Universita "La Sapienza" I Facolta, Roma (June 2008-March 2010)].
AB  - Fifty-nine children were enrolled in the Outpatient Health Care Package (OHCP)
      from 01/06/2008 to 31/03/2010. All children, except two, attended entirely the
      follow-up appointments; a satisfactory result, considering also that 30% of
      family were living outside the urban area and more than a third of the families
      was originated in a foreign country. At 3 months corrected age(CA) Haemoglobin
      mean values of 47 infants, all in iron treatment, were: 12.26 (10.1-14-1) g/dL;
      25% had values between 10.1 and 12 g/dL. Mean values for Calcium were 10.75 (9.50
      15.26) mg/dL Mean values for ALP were 393 (179-1075) UI/L, values >1000 UI/L were
      found in two infants who suspended Vitamin D treatment. At 3 months CA 50 infants
      performed ABR, 12 of these showing abnormalities. To date 9 infants repeated ABR
      at 6-9 months CA, 4 of these showed again abnormal results. Overall were found 4
      ABR abnormalities among 47 children (8.5%). Outcome of 23 children at 12 months
      CA: no moderate or severe neurologic abnormalities were found, 4 children (17.4%)
      presented mild abnormalities, 2 were referred for rehabilitation. No QSM <80% was
      found (mean QSM 93.7%) in 10 children evaluated. One child presented growth
      retardation <5 degrees; 2 underwent laser treatment for ROP with normal vision, 7
      (30.4%)had sistolic BP > or = 95 degrees; 6 (26%) were rehospitalized. This
      experience was positive: OHCP promoted a better compliance and standardization of
      follow-up. It would be desirable to prolong OHCP until school-age, including
      renal and cardiac functions monitoring.

PMID- 21090070
TI  - [Home care for the high-risk newborn infant].
AB  - With increased survival of extremely low birth weigh (ELBW) and very ill infants,
      a lot of them are discharged with unresolved medical issues that complicate their
      subsequent care. Infants born preterm with low birth weight who require neonatal
      intensive care experience a much higher rate of hospital readmission and death
      during the first year after birth compared with healthy term infants. Despite
      initial hospital care which is one of the most expensive of all kind of
      hospitalization, home care services are sometimes still sparse though the high
      risk of this group for failure to thrive, respiratory problems, developmental
      delays, parenting problems. In addition, societal and economic forces have come
      to bear on the timing and process of discharge and home care. Moreover it takes
      time for the family of a high-risk infant to prepare to care for their infant in
      a home setting and to obtain the necessary support services and mobilize
      community resources. Careful preparation for discharge, good follow-up and
      medical home after discharge may reduce these risks.

PMID- 21090071
TI  - [Delivery room intensive care unit].
AB  - Over the most recent 10 years there have been no significant further improvements
      in survival or morbidity rates of preterm infants, mostly the extremely-low
      gestational-age-neonates (ELGANs, defined as less than or equal to 28 weeks'
      gestation).The incidence of some of the major morbidities associated with extreme
      prematurity, such as BPD, could potentially be affected by management in the
      first minutes of life; it may be necessary to apply the principles of care that
      occur in the neonatal intensive care unit in the delivery room to achieve a
      further improvements in short and long-term outcome of these neonates. Up to now,
      the care of the smallest preterm infants in the delivery room has received little
      attention: few resuscitation protocols addressed to these newborns, not advanced
      equipment used and subjective monitoring based on clinical examination.
      Therefore, it may be useful to incorporate an intensive care environment into the
      delivery room to enhance survival rates and reduce morbidity of the extremely
      preterm infants. New approaches in the first minutes of life using more gentle
      parameters of intervention are being studied but further evidence is needed to
      improve resuscitation procedures in these newborns.

PMID- 21090073
TI  - [Surveillance of infection events in neonatal intensive care].
AB  - Nosocomial infections are one of the major causes of morbidity and mortality in
      the newborn intensive care unit (NICU). They result in prolonged hospital stays
      and increased hospital costs. Neonates are susceptible hosts because of
      prematurity of organ systems, immaturity of immune system, low birth weight and
      the use of invasive devices. Most infections are endemic others can occur during
      outbreaks. As advances in medical technology improve mortality in the tiniest of
      infants, it is imperative that health care providers identify effective
      interventions to minimize the risks of nosocomial infections in the NICU.
      Recommended infection control and prevention strategies are: hand washing
      promotion, decreased use of invasive procedures, limited antitibiotic exposure,
      environmental hygiene. In this context infection surveillance is the first step
      to recognize and analyze problems, to effectively target infection control
      measures and feedback. Any suspicion of an outbreak should lead to a review of
      general infection control procedures to prevent the spread of the pathogens as
      quickly as possible. A multidisciplinary approach can be an effective means of
      developing a plan of action to apply prolonged and strict adherence to isolation
      precautions', to detect potential reservoirs or source of infections, to educate
      every member of the patient care team and to review NICU protocols.

PMID- 21090072
TI  - [The newborn infant of a mother with tuberculosis].
AB  - TBC is a major infectious emergency in the world. OMS suggest that there are 8
      millions of affected every year and 2 millions of deaths. Italy is considered a
      country with low prevalence, but the increase of the immigration from Africa Asia
      and Est Europa (country with high risk) imposes attention to the problem. The
      delivery is a critical moment to investigate people at risk of disease. The
      infection of the newborn can happen intrauterine or in the expulsive period, but
      is possible also at home, from somebody affected by an active pulmonary disease.
      Diagnosis in the newborn is not easy for the aspecificity of clinical signs and
      for the frequent initial negativeness of Mantoux test. Culture of placenta,
      gastric aspirate, tracheal secretions, urine would be requested, cerebrospinal
      fluid if necessary. Neonatal disease needs therapy with isoniazide, rifampicine,
      pirazinamide and, or ethambutol, or streptomycin. Profilaxis of a newborn from a
      woman affected by an active form of tuberculosis or living with people affected
      by an active pulmonary form consists in giving isoniazide until diagnostic tests
      are negative and in removing the sicks (only with pulmonary disease). New
      dangerous kinds of pharmacological multiresistent tuberculosis are appeared in
      the last years in the world and, with the coinfection HIV-TBC and the
      reorganization of the surveillance system, represents the major obligation for
      the next years.

PMID- 21090074
TI  - [The well-being of the newborn infant in neonatal intensive care].
AB  - Patients referred to Neonatal Intensive Care Units are particularly vulnerable
      because they are in a critical or sensitive period of development. When
      physicians were first able to really save preemies 40 years ago, not much thought
      was given to their brain development. The babies we care for are so early that
      the brain cells are still migrating to where they will finally rest in developed
      brain. We are shaped, to an extent, by our environment. In early life, the
      environment takes on a particularly important role. So treatments may over
      stimulate areas of the brain with unknown consequences. For this reason minimally
      invasive treatments together with attention to the environment will favour a care
      developmentally appropriate for pre-term babies. Use of nasalCPAP, early rescue
      surfactant, synchronized mechanical ventilation, together with temperature, light
      and noise control could help to obtain these results. Pain control, music
      therapy, massage, kangaroo care and a family centred care are essential to
      optimize results obtained from the intensive care.

PMID- 21090075
TI  - [Macrosomic infants: clinical problems at birth and afterward].
AB  - Macrosomic infants (birth weight >4000 g) show increased risk for shoulder
      dystocia and associated injuries, hypoglycemia and respiratory distress. Higher
      risk is directly related to neonatal birth weight. High birth weight is also
      associated with increased risk of developing metabolic syndrome later in life.
      However the relation between birth weight and later-life metabolic syndrome in
      not linear, but "U" shaped.

PMID- 21090076
TI  - [The contribution of enteral nutrition in the premature infant].
AB  - In recent years, improvements in obstetrical and neonatal care have significantly
      improved survival in preterm and, particularily, the very low birth weight
      infant. Several studies stress the importance of timely and adequate nutrition in
      these high-risk infants on a short- and long-term. Presently, there is little
      consensus among the neonatologists concerning the optimal way to initiate,
      advance or maintain enteral feeding in preterm Infants. The preferred food for
      premature infants is fortified milk from the infant's own mother
      or,alternatively, formula designed for premature infants. The recent guidelines
      proposed by ESPGHAN Committee on Nutrition provide minimal and maximal levels of
      intake for individual macro- and micro-nutrients.

PMID- 21090077
TI  - [Growth and body composition in the premature infant].
AB  - Great interest has focused recently on the relationship between early nutrition,
      growth and subsequent health. Indeed, several studies have demonstrated that
      early life growth patterns exert programming effects on disease risk in later
      life, highlighting the key role played by early nutrition. Body composition, an
      index of quality of growth, is one of the factors apparently involved into this
      "programming" process. The American Academy of Pediatrics recommends to supply
      adequate amounts of nutrients so that growth and body composition of the preterm
      infant approximates that of the intrauterine fetus at the same gestational age.
      However, in clinical practice, the achievement of intrauterine growth rate and
      body composition is difficult Indeed, most preterm infants experience a
      significant postnatal growth retardation which can be accompanied by an increased
      and/or altered adiposity. The estimation of the dynamic features of body
      composition changes, in order to evaluate the quality, in addition to t he amount
      of weight gain plays a major role in the nutritional follow-up of preterm
      infants. Certainly, monitoring the somatic growth and the development of body
      composition in early infancy represents an extremely important clinical tool in
      the individualization of the nutritional management, the prevention and/or the
      recovery from the postnatal retardation and the identification of the subjects at
      high risk for developing the metabolic syndrome in young adulthood.

PMID- 21090078
TI  - [Chylothorax].
AB  - Chylothorax is the accumulation of chyle in the pleural space. In newborns the
      congenital form is often prenatal diagnosed, while the late variety originates to
      damage to the thoracic duct by cardiac surgery, diaphragmatic hernia, etc.
      Clinical presentation results from the accumulation of pleural fluid and the
      symptoms depends on the size of the effusion. The treatment needs both medical
      and surgical care. The pleural cavity should be drained via thoracocentesis, and
      total parenteral nutrition should be started. Afterward fat-free diet with the
      addition of medium-chain triglycerides could be initiate. Somatostatin and
      octreotide have been successfully employed, mainly in post-surgery chylothorax.
      Surgery should be considered when medical management fails. Some approaches are
      reported, and thoracic duct ligation, pleurodesis and pleuroperitoneal shunts are
      the most utilized. The prognosis of chylothorax depends on the etiology, and it
      is consequence of a variety of treatments that may influence the outcome.

PMID- 21090079
TI  - [Horizons of endoscopic surgery].
AB  - Minimally invasive surgery (MIS) has been one of the most important developments
      in surgery in the last century. By reducing the incision to small puncture
      wounds, morbidity, pain, adhesions and scarring are reduced. Due to their small
      size, neonates have not benefited from the advances in endoscopic surgery as
      rapidly as their adult counterparts. In the last 10 years, miniaturization of
      instruments and the development of sophisticated new techniques have enabled
      paediatric surgeons to apply endoscopic surgery to neonates. MIS is now being
      performed in both the neonatal chest and abdomen. This presentation will review
      these new developments and discuss the potential for even further improvements in
      neonatal surgery in the future. Also, a profile of the patient at risk for an
      insufflation-related incident and selection of neonates who will benefit most
      from these techniques in conditions of maximal safety will be drawn.

PMID- 21090080
TI  - [Validation of an hourly transcutaneous bilirubin nomogram in a population of
      term or late preterm newborn infants: preliminary results].
AB  - OBJECTIVE: The aim of this study was to asses the validity of the TCB nomogram
      for the European population for predicting significant hyperbilirubinemia in
      healthy term and late-preterm newborns. METHODS: This observational study was
      conducted from February 2009 to December 2009 in the well-baby nurseries of
      Gemelli hospital of Rome. The predictive ability of the skin bilirubin (TCB)
      nomogram was prospectively assessed in 926 neonates with gestational age ?35
      weeks. TCB was measured with Bilichek and total serum bilirubin (TSB) was
      contemporary assayed by the standard spectrophotometric method. Every neonate was
      assess for a single TCB and TSB value. RESULTS: The mean TSB values was 8.2 +/-
      3.2 mg/dl, while the mean TCB values was 9.5 +/- 3.6 mg/dl A sensitivity of 100%
      and a negative predictive value of 100% were obtained with a single bilirubin
      determination applying the 75 degrees percentile of our nomogram. CONCLUSION: The
      75 degrees percentile of the skin bilirubin nomogram for the European population
      in the first 96 hours of life is able to predict all neonates at risk of severe
      hyperbilirubinemia. It could facilitate a safe discharge from the hospital and a
      targeted intervention and follow-up reducing the need for blood samples.

PMID- 21090081
TI  - [From neonatal intensive care to pediatric intensive care: the physician's
      professional experience].

PMID- 21090082
TI  - [Ventilatory care].
AB  - Mechanical ventilation is considered a supportive, nontherapeutic technology used
      to perform the work of breathing for patients who are unable to do so on their
      own. In neonatology, mechanical ventilation is often used for premature neonates
      who are unable to sustain ventilation because of reduced functional residual
      capacity due to surfactant deficiency. Mechanical ventilation is thus an attempt
      to mimic the respiratory system's physiological function of gas exchange until
      the respiratory system reaches maturation. In pediatrics, mechanical ventilation
      is rarely used for acute respiratory distress syndrome as shown by Dahlem et al.
      in 2003 who found that only 9.9% of cases of respiratory failure in PICU was
      caused by ARDS. For this reason, ventilatory techniques in PICU are very
      heterogenous from the assisted to the most aggressive controlled modes associated
      with ventilator maneuvers. There are no specific guidelines for the use of
      mechanical ventilation in children and the low number of infants with ARDS in
      PICU makes it difficult to run randomized controlled trials in this population.
      Thus the algorithms are based on the results of either adult or neonatal studies.
      The advantage of extrapolating data from the neonatal evidence relates mainly to
      the prevention of ventilator induced lung injury (e.g., CPAP, HFOV, NIV,
      permissive hypercapnia, surfattant), of which neonatologists are particularly
      expert.

PMID- 21090083
TI  - [Assistenza cardiocircolatoria. (Cardio-circulatory care)].
AB  - Mortality in pediatric cardiovascular failure is markedly improved with the
      advent of neonatal and pediatric intensive care and with the implementation of
      treatment guidelines. In 2002 the American College of Critical Care Medicine
      Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal
      Shock reported mortality rates of 0%-5% in previously healthy and 10% in
      chronically ill children with septic shock associated with implementation of
      "best clinical practices". Early recognition of shock is the key to successful
      resuscitation in critically ill children. Often, shock results in or co-exists
      with myo-cardial dysfunction or acute lung injury. Recognition and appropriate
      management of these insults is crucial for successful outcomes. Resuscitation
      should be directed to restoration of tissue perfusion and normalization of
      cardiac and respiratory function. The underlying cause of shock should also be
      addressed urgently. The physiological response of individual children to shock
      resuscitation varies and is often unpredictable. Therefore, repeated assessments
      of vital parameters are needed for taking appropriate decisions. Global indices
      of tissue oxygen delivery help in targeting therapies more accurately. Isotonic
      fluids form the cornerstone of treatment and the amount required for
      resuscitation is based on etiologies and therapeutic response. After
      resuscitation has been initiated, targeted history and clinical evaluation must
      be performed to ascertain the cause of shock and management of co-morbidities
      should be implemented simultaneously. While the management of shock can be
      protocol based, the treatment needs to be individualized depending on the
      suspected etiology and therapeutic response particularly for children who suffer
      from congenital heart disease.

PMID- 21090084
TI  - [Markers of brain injury in non-invasive biological fluids].
AB  - Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain
      blood barrier permeability modifications leading to cerebral vascular
      autoregulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion
      are the main events involved in vascular auto-regulation loss leading to cell
      death and tissue damage. Reperfusion could be critical since organ damage,
      particularly of the brain, may be amplified during this period. An exaggerated
      activation of vasoactive agents, of calcium mediated effects could be responsible
      for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and
      damage. These phenomena represent a common repertoire in newborns complicated by
      perinatal acute or chronic hypoxia treated by risky procedures such as mechanical
      ventilation, nitric oxide supplementation, brain cooling, and extracorporeal
      membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period
      is crucial, as clinical symptoms and standard monitoring parameters may be silent
      at a time when brain damage is already occurring and the therapeutic window for
      pharmacological intervention is limited. Therefore, the measurement of
      circulating biochemical markers of brain damage, such as vasoactive agents and
      nervous tissue peptides is eagerly awaited in clinical practice to detect high
      risk newborns. The present article is aimed at investigating the role of dosage
      biochemical markers in non-invasive biological fluids such as S100B, a calcium
      binding protein, activin A, a protein expressed in Central nervous System (CNS).

PMID- 21090085
TI  - [Chorioamnionitis in the delivery room].
AB  - Chorioamnionitis (CA) is defined as an infection that can affect amniotic fluid,
      placenta and uterus. The chorioamnionitis is present in 10-40% of cases of
      maternal peripartum fever and in 50% of preterm labor. Diagnosis is based on the
      presence of maternal fever (>38 degrees C) at least 2 of these conditions:
      maternal leukocytosis (> 15,000 cells/mmc), maternal tachycardia, fetal
      tachycardia, stained or foul smelling amniotic fluid, uterine tenderness.
      Obstetric risk factors include nulliparity, presence of stained amniotic fluid,
      the excessive duration of labor, the presence of pathogens in the genital tract
      (eg, Gonorrhea, GBS, EC), and the frequency of digital vaginal examinations. In
      suspicion of CA membranes and placenta are usually sent for histological
      examination performance, but the diagnosis of CS is not always confirmed by
      histological or microbiological exams. Early administration of broad-spectrum
      antibiotic therapy reduces both maternal and neonatal morbidity. The standard
      treatment by the administration of ampicillin and gentamicin have been shown to
      be safe and effective. Common maternal complications include bacteremia to septic
      shock, cesarean section, uterine atony with hemorrhage, pelvic abscess, maternal
      coagulopathy, thromboembolism and wound infections. The risk of neonatal sepsis,
      low seizures, low Apgar score at 5 minutes increased in the newborn.
      Cardiotocographic fetal monitoring should be continued during labor in cases of
      suspected chorioamnionitis with recourse to caesarean section as soon as signs of
      severe fetal distress.

PMID- 21090086
TI  - [Chorioamnionitis and inflammatory disease in the premature newborn infant].
AB  - Preterm births occurs in 6-12% of all pregnancies, accounts for 75% of neonatal
      death and causes significant neonatal morbidity. A large number of preterm birth
      is associated with infection (30%), because of the release of many cytokines. In
      fact acute chorioamnionitis represents the inflammatory response to extracellular
      microorganisms that gain access to the gestational sac. Clinical signs of
      infection compare in the 12% of cases, while the prevalence of positive amniotic
      fluid cultures is approximately 50% in patients with preterm PROM. Despite the
      recent studies about the dosage of inflammatory biomarkers in the amniotic fluid
      or in fetal and maternal blood, placenta histology remains the gold standard for
      the diagnosis of chorioamnionitis. Histological chorioamnionitis describes the
      progression of the inflammatory process. Organisms first colonise the
      chorioamnionic surface. Then, the neutrophils migrates to the chorion
      (chorionitis) and to the amnion (chorioamnionitis) and, in the last stage,
      amnionic epithelial cells undergo necrosis (necrotising chorioamnionitis). It
      represents the mother inflammatory response and it differs from the fetal
      inflammatory response (funisitis). Funisitis first appears in vessels of the
      chorionic plate (chorionic vasculitis) or in the umbilical vein (umbilical
      phlebitis), then in the umbilical artery (umbilical arteritis), and in the
      Wharton's jelly (umbilical perivasculitis). The fetal inflammatory response has
      been associated with inflammatory diseases of preterm infants, increasing the
      risk of neonatal sepsis and meningitis, bronchopulmonary dysplasia and cerebral
      palsy. We present our experience on the relationship between histological
      chorioamnionitis, preterm birth and inflammatory diseases of VLBW infants.

PMID- 21090087
TI  - [Disinfectants for the skin of premature].
AB  - Nosocomial infections are among the leading causes of mortality and morbidity in
      neonatal intensive care units. Prevention of healthcare-associated infections is
      based on strategies that aim to limit susceptibility to infections by enhancing
      host defences, interrupting trasmission of organisms by healthcare workers and by
      promoting the judicious use of antimicrobials. Strategies for the prevention of
      nosocomial infections include hand hygiene practices, prevention of central
      venous (cvc)-related bloodstream infections, judicious use of antimicrobials for
      therapy, enhancement of host defences, skin care and early enteral feeding with
      human milk. Major concerns about the use of alcoholic chlorhexidine are for the
      high risk of skin burns in extremely premature infants during the first days of
      life, when the skin is thin and not fully keratinesed. Aqueous chlorhexidine
      could be less irritant when used in very low birthweigth infants and thus could
      represent a good option. A recent prospective trial of adult patients showed
      similar effectiveness of alcoholic and aqueos solutions of chlorexidine. However,
      to date no study evaluated whether the aqueos formulation is less harmful and as
      effective as the alcoholic formulation in neonatal infants. The lack of evidence
      for neonatal patients prompts urgent need for large randomised controlled trials
      comparing effectiveness and safety of different skin disinfectants before CVC
      placement in neonates and particulary in very low birth-weight infants.
      Nosocomial infections are still of the most serious problems for the neonatal
      intensive care unit. Therefore every effort must be implemented to reduce the
      incidence of these infections, can not be considered a toll required
      hospitalization, as it may not be acceptable for a place of shelter and care as
      the hospital may itself be a source of disease.

PMID- 21090088
TI  - [PICC: central venous access by the peripheral route. Medical-nursing aspects].
AB  - To have access to central vein, for the infant in NICU,often have a role, for
      their, life-preserving. The increase of survival in the VLBW, and specially in
      the ELBW,is guaranteed, in the first days of the life also by a safe vascular
      access, in fact we can, in this way, to supply with parenteral nutrition to all
      the requirements that these special patients have. In the first approach to the
      seriously ill newborn, the umbilical vessels, are the first choice to use,we have
      the way more fast, stable and easy, to guarantee: the emergency therapy,
      monitoring and caloric requirements. After 6-7 days, however, specially in the
      ELBW, it is important to find a more stable vascular access, through we can to
      provide high osmolarity solutions without complications, to supplement the MEF
      (Minimal Enteral Feeding) with parenteral nutrition optimizing energy intake and
      caloric. At this time, for the preterm baby is more safe and easy choice the
      central venous catheter peripherally inserted (PICC). The Authors assess the
      medical nurse aspects related to this method starting from the choice of vase,
      the techniques of cannulation and dressing, then linger on the management and
      prevention of complications. We will, finally, show our data on PICC related to
      212 preterms admitted in our NICU with weight <1500 gr and/o E.G. <30 ws.; from
      the year 2006 to 2009, that correspond to the our precence to the Vermont Oxford
      Network (VON).

PMID- 21090089
TI  - [Management of pleural drainage].
AB  - In the neonatal population, pleural effusion and particularly tension
      pneumothorax can be a deadly situation. Pneumothorax occurs more often in the
      neonatal period that any other time of life. Tension pneumothorax can result in
      very high pressures within the pleural space, collapsing the lung on the involved
      side and resulting in immediate hypoxia, hypercapnia and subsequent circulatory
      collapse. For these reasons, the ability to recognize, understand and treat these
      pathologies is essential for neonatal health and a good outcome. Neonates have
      many factors that can contribute to. these problems. These include respiratory
      distress syndrome, mechanical ventilation, sepsis, pneumonia, aspiration of
      meconium, congentital malformation, hydrothorax, congenital or acquired
      chylothorax. The diagnosis can be made by clinical examination, transillumination
      (pneumothorax) and chest x-ray. Besides, lung ultrasound constitutes a visual
      medicine and provides a transparent approach to the acutely ill patient, newborn
      included, guiding diagnosis, management and care. Newborns with moderate to
      severe symptoms and those receiving positive pressure ventilation require tube
      thoracostomy. If a tension pneumothorax is suspected, emergency needle
      decompression in the second intercostal space in the midclavicular line is
      required. In this article, we describe the management of tube thoracostomy using
      trocar tubes or pigtail catheters. Besides, we pay attention to the use of pain
      control for neonates undergoing painful procedures such as chest tube insertion.

PMID- 21090090
TI  - [The assistance of the ventilated infant: role of the nurse in the management of
      the endotracheal tube].
AB  - One of the principal duties of a staff nurse working in a NICU is the assistance
      of the ventilated infants. The management of the endotracheal tube is a key
      moment in the neonatal care and it is fundamental to prevent the ventilator
      induced lung injury and the change in the perfusion (especially in the brain)
      that may determine an impairment of gas exchange. Therefore, the role of the
      staff nurse is to guarantee that the tube remains correctly placed and firmly
      fixed in order to avoid tubes displacement and accidental extubations. High
      production of bronchial secretion may lead to a tube obstruction, partial or
      complete, that can cause formation of atelectasic areas as consequence of
      impaired ventilation. Tracheal suction may reduce this adverse event, but it is
      associated with hypoxic events, cardiocirculatory instability and can determine
      an increase in the endocranial pressure. Actually the scientific literature is
      poor in guidelines about the frequency, the duration, the level of pressure and
      the material to use in tracheal suctioning. The tracheal suction is a complicated
      intervention; to be well performed, it needs the nurse having a good observation
      capacity, a knowledge of the infant's pulmonary disease and, moreover, it
      requires that the nurse is acknowledged of the modality of the respiratory
      assistance of the infant. Therefore, this procedure is specifically patient
      oriented. In this review we analyze the scientific literature about the nurse
      management of the ventilated infant, and we report our personal experience about
      the strategy in reducing adverse effects as the loosing of end expiration lung
      volume and the accidental extubations.

PMID- 21090091
TI  - [Electrocardiography by the neonatologist].
AB  - An electrocardiogram is a simple, non-invasive and inexpensive test, whose
      knowledge and interpretation should be an essential skill for neonatologists. It
      is a basic, easy and handy tool, very useful for the right approach to the child
      with suspected heart disease. The test provides important information on the
      heart rhythm and is essential to diagnose and therefore treat arrhythmic
      problems. It gives also information on the ventricular dimensions and volume
      and/or pressure overload of one or both ventricles. In case of malformative
      pathologies, the test enables to suspect the type of malformation. The aim of
      this report is to explain a normal electrocardiogram in a practical and simple
      way, through the definition of the necessary basic criteria to detect heart rate
      and rhythm, electrical axis of QRS complex, normal wave morphology in all leads
      and atrioventricular conduction (PR interval). Some basic information will also
      be provided on how to recognize a pathological electrocardiogram and heart rhythm
      disorders. Then we will use interactive methods to discuss some tracings through
      which it will be possible to reach a diagnostic orientation.

PMID- 21090092
TI  - [Aspects of neonatal care].

PMID- 21090093
TI  - [The newborn infant with a suspected malformation syndrome].
AB  - Congenital malformations occur in 2-3% of live births, and often represent a
      special diagnostic and management challenge. Few clinical guidelines exist to
      assist the neonatologist in the approach to diagnosis and initial management of
      the malformed newborn. To provide optimal care for these children, one must
      employ a systematic approach to identify the likely pathogenic mechanism leading
      to the birth defects present. Determining how distinct anomalies relate to one
      another may lead to elucidation of a specific genetic etiology for the patient's
      condition. Genetic testing is increasingly available to allow for diagnostic
      confirmation. Using this systematic approach to a child with congenital anomalies
      permits accurate prognostic and recurrence risk counseling, informed management
      decisions, and the appropriate allocation of social support and medical
      resources.

PMID- 21090094
TI  - [Practical strategies for promoting breastfeeding in neonatal intensive care].
AB  - Strategies for promoting the use of human milk in NICU Human milk has several
      advantages in the nutrition of very-low-birthweight (VLBW) and high risk infants
      admitted to neonatal intensive care unit (NICU). Limited data available
      demonstrate that at discharge from NICU breastfeeding rate is relatively low. In
      a recent italian study (Davanzo R et aL; Pediatric and Perinatal Epidemiology
      2009) only 30.5% of VLBW infants were exclusively breast fed and among the
      exclusively breastfed infants only 10% sucked directly at the breast. Strategies
      to promote breastfeeding and the use of human milk in NICUs are needed. They are
      well known, yet limitedly applied. Among them current literature lists: (1)
      access at anytime for both parents to NICU; (2) specific knowledge of the science
      of lactation and multidisciplinary breastfeeding training as provided by the Baby
      Friendly Hospital Training package; (3) peer support in hospital; (4) kangaroo
      mother care; (5) breastmilk expression using simultaneous pumping with an
      electric pump particularly in the first 2 weeks. On the contrary, pharmaceutical
      galactagogues and cup feeding have little benefit.

PMID- 21090095
TI  - [From tube to breast].
AB  - WHO suggests exclusive maternal milk up to six months of life. This clue is much
      more important refer to premature newborn. Everybody knows the several advantages
      of human milk versus formula milk. We can also say that supporting maternal
      feeding in NICU helps woman that probably lives a complicated relationship with
      her "being mother" and with her baby. We can help the couple mother-newborn and
      their family to build strong basement for their future relationship, whatever it
      will be. The main aspects are: precocious and frequent stimulation of the breast;
      counseling; NIDCAP; kangaroo mother care; 24 hours open NICU; feeding consultant;
      teamwork In presence of these elements in NICU will be easier involve the mother
      and propose her some practices that could help her and her baby in breastfeeding.

PMID- 21090096
TI  - [Introduction to the principles of neonatal resuscitation].
AB  - WHO has estimated that as many as 10% of all newborn infants need some
      intervention at birth and approximately 1% more extensive intervention. If this
      is correct, up to 13-14 million of the world's annual newborn infants need
      intervention and of these approximately 1.5 million will need intensive therapy.
      Each year at least 1.16 million newborn babies die in sub-Saharan Africa. This
      region has the highest risk of newborn deaths and the slowest progress in
      reducing mortality. The transition from intrauterine to extrauterine life is
      extremely hazardous, with probably more radical physiologic adjustments required
      during and immediately following the birth process than at any other point in a
      human lifetime. Although certain episodes of fetal asphyxia cannot be prevented a
      prompt and skilled resuscitation may prevent lifelong adverse sequelae. Optimal
      resuscitation procedures should therefore become high priority. The ILCOR, the
      AHA and the AAP have established their new guidelines for newborn resuscitation
      on review of the evidence for each step. There still are a number of unanswered
      questions regarding newborn resuscitation (the ideal ratio of chest compressions
      to ventilation, the benefits and risks of supplementary oxygen, the indications
      for volume therapy, the optimal glucose level in infants that required
      resuscitation, the better ventilation in a newborn at birth.

PMID- 21090097
TI  - [Effect of topical corticosteroids on expression of PKC, Bcl-2 and Bax in nasal
      polyps].
AB  - OBJECTIVE: To study the effect of intranasal glucosteroid on the expression of
      PKC, Bcl-2 and Bax in nasal polyps. METHOD: The expression of PKC, Bcl-2 protein
      and Bax were detected with immunohistochemistry in nasal polyps from the patients
      (n=16) pre and post treated for 4 weeks with intranasal glucosteroid. And which
      compared with normal mucous membrane of inferior turbinate concha. RESULT: The
      PKC and Bcl-2 protein expressed significantly higher in the pretreated patients
      (P < 0.01), which were significant reduced in the post treated patients compared
      with pretreated ones. The expression of Bax protein significantly higher in the
      post treated patients (P < 0.05). CONCLUSION: Our findings indicated that
      abnormal expression of apoptosis related genes in nasal polyps tissues might play
      an important role in the occurrence and progression of nasal polyps. The
      treatment of intranasal glucosteroid may regulate the expression of apoptosis
      related genes.

PMID- 21090098
TI  - [HIF-1alpha and CA IX expression in nasal polyps and study on their correlation].
AB  - OBJECTIVE: To analyze the expression and relationship between hypoxia inducible
      factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CA IX) in nasal polyps, and
      to explore the role of HIF-1alpha and CA IX in the pathogenesis of nasal polyps.
      METHOD: Twenty-eight tissues of nasal polyps and 12 tissues of normal inferior
      turbinate mucosa were collected in this study. And Immunohistochemistry method
      was used to detect the expression of HIF-1alpha and CA IX in the two groups.
      RESULT: The numbers and intensity of positive stained cells of HIF-1alpha and CA
      IX were higher in nasal polyps. IOD of HIF-1alphaa and CA IX (10(3)/HP) in the
      nasal polyps were respectively 21.76 +/- 3.52, 26.87 +/- 4.60 compared with 3.37
      +/- 1.65, 3.25 +/- l.20 in the control group by image analysis. There were
      significant differences between the two groups (P < 0.05). Spearman correlation
      test showed that there was a close correlation between the HIF-1alpha and CA IX
      expression in nasal polyps (r = 0.820, P < 0.01). CONCLUSION: The results showed
      that HIF-1alpha and CA IX were over expressed in nasal polyps, and there was a
      close correlation between them. Hypoxia was found in nasal polyps and it could
      become more severe under infection, inflammation and energy metabolic disorder
      which consumed a great deal of oxygen. HIF-1alpha was over expressed in nasal
      polyps, which activate and promote the expression for CA IX, in order to keep the
      normal pH of cells for adapting the hypoxic microenvironment and sustain
      persistent growth and hyperblastosis of cells in the hypoxic areas. At last the
      internal circle was forming, which accelerate the formation of nasal polyps.

PMID- 21090099
TI  - [Nasal anatomic abnormalities and bacterial infection in chronic rhino
      sinusitis].
AB  - OBJECTIVE: To study the relationship between nasal anatomic abnormalities and the
      bacteria infection status of maxillary sinus. METHOD: The anatomic abnormalities
      of 115 cases of maxillary sinuses were detected with the CT images and confirmed
      with chronic infection, which were divided into two groups: high anatomic
      abnormality group and low anatomic abnormality group. The sinusal contents were
      sent to bacteria culture, compare the bacteria infection rate and the
      distribution of bacteria between the two groups. RESULT: The bacteria positive
      rate of the high anatomic abnormality group and low anatomic abnormality group
      was 90.32% and 56.60% (P < 0.01) respectively. The contribution of gram-positive
      bacteria and gram-negative bacteria are 47.76% and 52.24% in high anatomic
      abnormality group, 62.16% and 37.84% in low anatomic abnormality group.
      CONCLUSION: Nasal anatomic abnormalities can improve the bacteria infectious rate
      of maxillary sinuses. High anatomic abnormality may more induces gram-negative
      bacteria infections,while low anatomic abnormality may more induces gram-positive
      bacteria infections.

PMID- 21090100
TI  - [Resection of anterior skull base cranio-nasal communication tumors via the inner
      plate of frontal sinus-epidural approach].
AB  - OBJECTIVE: To explore the application of inner plate of frontal sinus-epidural
      approach in the treatment of anterior skull base cranio-nasal communication
      tumors. METHOD: A study of 6 cranio-nasal communication tumor patients was
      undertaken. They were treated with lateral rhinotomy-inner plate of frontal sinus
      epidural approach to remove tumor. RESULT: The tumors in all the 6 patients were
      completely resected. The follow-up study during the following 2 years revealed
      that 5 patients had good facial appearances and showed no tumor recurrence, no
      cerebrospinal rhinorrhea, no meningoencephalocele, no frontal collapse, and other
      complications. CONCLUSION: The surgical approach in the treatment of Cranio-nasal
      communication tumors needs to be chosen according to the tumor size, location and
      nature. Lateral rhinotomy-inner plate of frontal sinus-epidural approach can be
      carried out independently by the head and neck surgeons. It is a valuable
      surgical treatment with minimal invasion, short surgery time, little damage to
      brain, and easy pyrosis of skull base.

PMID- 21090101
TI  - [The long-term morphology of the nasal cavity after total laryngectomy].
AB  - OBJECTIVE: To investigate the long-term effect of nasal airflow deprivation on
      nasal dimensions after total laryngectomy. METHOD: Thirty-two patients with total
      laryngectomy were enrolled in the study. Acoustic rhinometry was used to measure
      the minimum cross-sectional area (MCSA) and the volume of the nasal cavity after
      laryngectomy, compared with the normal control group. In addition, patients
      underwent endoscopic nasal examinations and answered questionnaires
      postoperatively, symptoms between the different levels to compare the results of
      acoustic rhinometry. RESULT: At both within 1-year and more than 1-year follow
      ups, the mean MCSAs and the mean nasal volumes were significantly expanded than
      the control values (P < 0.05). The nasal MCSA, nasal cavity volume was no
      significant difference between more than one year and less than 1 year group (P >
      0.05). The endoscopic examinations revealed only a deterioration in the
      appearance of the nasal mucosa over the long term. Survey showed that the
      postoperative patients had varying degrees of nasal obstruction flu, nose dry,
      hyposmia, etc. The nasal MCSA, nasal cavity volume was of the largest when
      moderate nasal obstruction flu,or severe dry nose or severe hyposmia. CONCLUSION:
      The structure was atrophic nasal change, the nasal MCSA, nasal cavity volume were
      larger, the results of acoustic rhinometry was different among the varying
      degrees of symptoms after total laryngectomy.

PMID- 21090102
TI  - [A clinical evaluation on correction of the deviated nose and functional
      reconstructive nasal surgery].
AB  - OBJECTIVE: To explore an effective method of correction of deviated nose and
      functional reconstructive nasal surgery. METHOD: Among 102 patients 32 cases were
      treated by septoplasty only, 53 cases were corrected by bony pyramid, 3 cases
      with severe asymmetry of bony pyramid by wedge resection and 14 cases by the
      implant of the septal or rip cartilage. RESULT: The successful rate was 92.20%
      (92/102) with period of 6 to 24 months follow up. CONCLUSION: Correcting the
      deviated nose to reconstruct its function with the intranasal approach and
      multiple techniques, can benefit both the cosmetology and nasal functional
      improvement. Rectifying the nasal septum, debonding the tissue of the deviated
      section completely, and fixing reconstructive structures are the keys for the
      successful result.

PMID- 21090103
TI  - [Nasal extranodal NK/T cell lymphoma: terminologic evaluation and diagnostic
      problems].
AB  - OBJECTIVE: To review on the evolution in the understanding of midline destructive
      lesions of the sinonasal tract in different period, and to describe the clinical
      features and diagnostic problems on the nasal extranodal NK/T cell lymphoma
      (NENKTCL). METHOD: To retrospectively study the nasal CT scannings and the
      results of serum ANCA of 10 patients with typical clinical characteristics.
      RESULT: All patients presented with the symptoms of the nasal obstruction and the
      nasal discharge. Epistaxis and facial swelling were in the clinical spectrum.
      Nasal endoscopy and CT scan of paranasal sinuses showed destructive sinonasal
      lesions. Ten patients were finally diagnosed as having NENKTCL by the pathologic
      findings combined with immunohistochemical phenotyping. Clinically, Nasal lesions
      in the cases were similar to those from historical nomenclature. CONCLUSION:
      Outdated terminology referring to midline lesions includes a variety of diseases,
      and NENKTCL is an independent disease focusing on destructive lesions of face and
      nose.

PMID- 21090104
TI  - [Construction and identification of eukaryotic plasmid pGC-silencer
      U6/Neo/GFP/ABCG2].
AB  - OBJECTIVE: To construct three short hairpin RNA (shRNA) interference expression
      plasmid vectors of human ABCG2 gene, to assay the expression of ABCG2 in a human
      nasopharyngeal carcinoma (NPC) cell line, CEN-2 cell line, and to detect the RNAi
      effect of shRNA. METHOD: Targeting ABCG2 gene sequence, three plasmid expression
      vectors coding for shRNA and a control vector containing random DNA fragment were
      constructed. The recombinant plasmids were amplified in Ecoli. DH5 and then
      identified by restriction digestion, PCR and sequencing. The recombinant plasmids
      were transfected into CEN-2 cells. ABCG2 expression was assayed by real-time
      quantitative PCR and Western blot. RESULT: The construction of pGC-silencer
      U6/Neo/GFP/ABCG2 was succeed. The shRNA plasmids significantly down-regulated the
      ABCG2 expression in CEN-2 cells, at both mRNA level and protein level.
      Recombinant plasmid 1 had the strongest effect compared with plasmids 2 and 3 (P
      < 0.05), with an inhibition ratio of 75% at the mRNA level and 68% at the protein
      level. CONCLUSION: pGC-silencer-U6/Neo/GFP/ABCG2 has been successfully
      constructed and it can down-regulate ABCG2 expression after transfected into CEN
      2 cells, which could help further studies of ABCG2 functions CEN-2 cell line and
      contribute to the NPC gene therapy.

PMID- 21090105
TI  - [Progress in using Newcastle disease virus for tumor therapy: a review].
AB  - Naturally existing Newcastle disease virus (NDV) can specifically execute
      oncolytic ability in clinical studies. Reports from clinical trials using NDV as
      oncolytic agents showed promise and warrant results in cancer therapy. In recent
      years, reverse genetics technology has been used widely in the studies of NDV
      virology. More recently, the technology was applied to optimize the oncolytic
      efficacy of NDV, for instance, modification of the F gene, and expression of GM
      CSF, IFN-gamma, IL-2 or TNF-alpha. NDV is widely investigated in cancer therapy
      and will definitely offer a prosperous future for clinical cancer therapeutics.
      We reviewed the developments of cancer therapy by recombinant NDV using reverse
      genetics technology, as well as our own experience in this domain.

PMID- 21090106
TI  - [Screening of proteins interacting with avian influenza virus nucleoprotein by
      yeast two-hybrid system in human brain cDNA library].
AB  - Avian influenza virus Nucleoprotein (NP) is important in viral transcription,
      replication and determining host specificity of influenza virus. Yeast two-hybrid
      technique was applied to screen for proteins interacting with virus
      nucleoprotein, so as to further elucidate the interaction between virus
      nucleoprotein and cellular proteins, as well as the interaction between virus and
      host. To explore new proteins interacted with NP protein, a human brain cDNA
      library was screened using yeast two-hybrid system with NP as the bait. DNA
      inserts of the positive AD/library plasmids were sequenced. By the BLAST analysis
      against the GenBank databases seven positive clones resulted in seven genes. Our
      results could help for the further study on the molecular mechanism of virus
      replication, transcription and protein-protein interaction. Further
      investigations were needed to characterize these interactions.

PMID- 21090107
TI  - [Effect and underlying mechanism of resveratol on porcine primary preadipocyte
      apoptosis].
AB  - We demonstrated the effect of resveratrol on porcine primary preadipocytes
      apoptosis, to study the intracellular molecular mechanism. Porcine primary
      preadipocyte was treated with different concentration of resveratrol (0
      micromol/L, 50 micromol/L, 100 micromol/L, 200 micromol/L, 400 micromol/L). We
      used optical microscope and fluorescence microscope to observe morphological
      changes during apoptosis after Hoechst 33258 Fluorescent dyes staining; and RT
      PCR and Western blotting to measure the expression of apoptosis-associated gene
      sirt1, caspase-3, bcl-2, bax, p53, NF-kappaB. Primary preadipocyte apoptosis was
      apparent, accompanied by reduced cell volume, chromatin condensation, and nuclear
      shrinkage. Compared to the control and low concentration group, high dose group
      (200 micromol/L) significantly increased the ratio of primary preadipocyte
      apoptosis. The expression of sirt1, caspase-3, and bax was up-regulated markedly
      in response to resveratrol; in contrast, apoptotic inhibitor bcl-2, p53, NF
      kappaB down-regulated. We further proved fact that resveratrol can specifically
      promote the activity of sirt1; moreover, activated sirt1 modulates the activity
      of caspase-3 and bcl-2 family, involving in transcriptional regulation of p53 and
      NF-kappaB through antagonizing factor-induced acetylation. Taken together, our
      data established resveratrol as new regulator in porcine primary preadipocyte
      apoptosis via activating the expression of sirt1, modulating activity of
      apoptotic-associated factor.

PMID- 21090108
TI  - [Ovine Follistatin gene expression and functional analysis of follistatin
      domains].
AB  - In order to study ovine follistatin function, we amplified the total of 1038 base
      pair of ovine complete follistatin cDNA and cloned into pGEM-T vector by RT-PCR
      from ovine ovary RNA. After removal of the signal peptide it was subcloned into
      the pET41a to construct the prokaryotic expression vector, named pFSsig-. SDS
      PAGE and Western blotting identified the 66 kDa product of the expression of
      follistatin cDNA. Based on the complete CDS sequence, we cloned follistatin N
      terminal domain and domain 1 with PCR and inserted into pLEX-MCS lentiviral
      vector, named pFS-N+D1. After package and passage of lentivirus in 293T cells,
      and then infected sheep primary muscle cells (SPMC). The expression of FS N+D1 in
      SPMC was assayed by Western blotting. The cell growth curve of the infected SPMC
      and noninfected control cells displayed that FS N+D1 stablly transfected SPMC
      proliferated significantly faster than the control cells (P < 0.01). Our data
      inferred that ovine FS N+D1 domain had the function to stimulate sheep muscle
      cell growth.

PMID- 21090109
TI  - [Construction and immunogenicity of recombinant porcine parvovirus-like particles
      with somatostatin].
AB  - In order to obtain a virus-like particle vaccine both for porcine parvovirus
      (PPV) prevention and growth-promotion, VP2 gene of PPV NJ-a strain was amplified
      with PCR, and four copies of synthetic somatostatin gene were fused to the N
      terminal of VP2 gene. The fused gene was cloned into pFast-HT A to construct the
      recombinant plasmid pFast-SS4-VP2, then the pFast-SS4-VP2 was transformed into
      DH10Bac competent cells and recombined with shuttle vector Bacmid, followed by
      identification with blue-white screening and PCR analysis for three cycles, and
      the positive recombinant was named as rBacmid-SS4-VP2. The positive Sf-9 cells
      were transfected with rBacmid-SS4-VP2 by Lipofectamine to produce recombinant
      baculovirus. When the cytopathic effect (CPE) was obvious, the transfected Sf-9
      cell was harvested, and the positive recombinant virus was named as rBac-SS4-VP2.
      The insertion for the target gene into baculovirus genome was confirmed with PCR.
      SDS-PAGE and Western blotting revealed that the calculated protein of
      approximately 68 kDa was in the expressed in the insect cells. The Sf-9 cells
      infected with rBac-SS4-VP2 were stained positive against PPV antibody using the
      indirect immunofluorescence assay (IFA). Moreover, the virus particle self
      assembly was observed under electron microscopy. 90 four-week-old mice were
      immunized by the recombinant protein coupled with different adjuvants alhydrogel,
      IMS and oil. VP2-specific ELISA antibodies, PPV-specific neutralizing antibody,
      somatostatin antibody and growth hormone levels were examined to evaluate the
      immunogenicity of this virus like particle. Results indicated that mice groups
      immunized rSS4-VP2 protein with alhydrogel and IMS developed similar humoral
      immune response comparing with inactived PPV vaccine. Mice group immunized with
      rSS4-VP2 generated higher level of SS antibody and growth hormone comparing with
      negative control, mice receiving rSS4-VP2 with alhydrogel developed the highest
      antibody titre than all other groups, while the oil group developed the lowest
      antibody level. This study provides not only a new rout for production of safe
      and effective virus like particle subunit vaccine, but also the foundations for
      peptide presentation and multivalent subunit vaccine design.

PMID- 21090110
TI  - [Expression of the hemagglutinin and neuramidinase gene of influenza A virus H1N1
      in Pichia methanolica].
AB  - On the basis of successful cloning the full length hemagglulinin (HA) and
      neuramidinase (NA) gene and sequence analysis of influenza virus H1N1, part of
      the gene was ligated into pMETA. Expression vectors pMETA/HA (52-1 557 bp) and
      pMETA/NA (121-1 263 bp) were constructed and expressed in pMAD16 induced by
      methanol. Recombinant protein was purified through Ni2+ affinity chromatography.
      Western blotting and ELISA were used to determine the antigenic activity of the
      recombinant protein. SDS-PAGE showed that the recombinant capsid gene could be
      overexpressed in Pichia methanolica. ELISA and Western blotting showed that the
      recombinant protein had antigenicity.

PMID- 21090111
TI  - [Effect of pH on growth and lipid content of Chlorella vulgaris cultured in
      biogas slurry].
AB  - Using 50% biogas slurry as basic medium, we investigated the effect of pH on the
      growth and lipid accumulation of Chlorella vulgaris. Setting two-group
      experiments, one was only control the initial medium pH, the initial pH was set
      at 6.0, 6.5, 7.0, 7.5, 8.0, and 8.5, respectively. One was control the medium pH
      constant, set constant pH at 6.0, 6.5, 7.0, 7.5, 8.0, and 8.5, respectively.
      Using HCl and NaOH regulated the pH. Results showed that algae Chlorella vulgaris
      grows better at pH 6.5 and 7.0, accumulate the lipid at pH 7.0-8.5, so the
      optimal pH for the growth and the lipid accumulation of Chlorella vulgaris was
      7.0. The average removal rate of nitrate from biogas slurry was 95%, phosphate
      was 97%.

PMID- 21090112
TI  - [Isolation, purification and structure analysis of polysaccharides from
      Peacilomyces lilacinus].
AB  - The paper dealt with the characterization of polysaccharide of Paecilomyces
      lilacinus NH-PL-03 strain. First, we extracted and purified exude polysaccharide
      from the fungal fermentation broth by ethanol depositing method. Second, the
      proteins were removed by the Sevage method from the crude polysaccharide. Third,
      the purified polysaccharide (EP-1) was obtained after Superdex G-75 column
      separation. The results of UV-spectrometer and Sephacryl S-200 HR chromatography
      experiments showed that the EP-1 was a homogeneous pure polysaccharide with
      molecular weight of 35.2 kDa. Tested by paper chromatography analysis using the
      complete hydrolysis by sulfuric acid, we found that the EP-1 comprise single
      component as glucose. The chemical structure of EP-1 was confirmed as a kind of
      linear glucan linked by beta-(1,3) linkage. The Congo red reaction performed that
      EP-1 probable presented a triple-helical conformation in the dilute alkali.

PMID- 21090113
TI  - [Influence of Japanese enciphalitis virus capsid protein on the self-replicate
      ability of JEV replicon vectors].
AB  - To optimize a self-replicate Japanese enciphalitis virus (JEV) replicon, and to
      make it as an efficient vector to express the heterologous protein, we
      constructed three JEV replicons by PCR-based shortening the length of capsid
      genes. The vectors remained full or part of C gene, based on the JEV replicon
      pCTCJEV. Lac Z was selected as the reporter gene to verify the self-replicate
      ability of these DNA-based replicons. While transfected into the cell lines CME
      4, which continuously expressing the JEV structure proteins C-prM-E, the JEV
      replicons pCMW-2M-1LACZ, pCMW-2M-3LACZ, which remained the first 23aa and 68aa of
      C protein, can express the reporter protein as the same level as pCMW-2M-LACZ
      with the full-length C protein. These results illustrated that the JEV replicon
      vector with 69-nt of the C gene can retain the self-replicate ability, and
      provide valuable tools to construct a possible vector for a long-lasting JEV RNA
      virus expression system.

PMID- 21090114
TI  - [DNA polymerase delta-interacting protein 38 is a target gene of microRNA-291a
      5p].
AB  - DNA polymerase delta-interacting protein 38 (PDIP38) was identified in 2003 as a
      human DNA polymerase delta interacting protein which plays important roles in DNA
      repair, mitosis and vascular smooth muscle cells (VSMCs) migration. Our previous
      study showed that PDIP38 was expressed in mouse embryonic stem (ES) cells and
      upregulated in protein levels after differentiation from ES cells, while the
      expression in mRNA levels was not changed. We supposed that microRNA played key
      roles in the regulation of PDIP38 and the differentiation of ES cells. By
      bioinformatics assay, we predicted that PDIP38 was a potential target of microRNA
      -291a-5p (miR-291a-5p). Furthermore, we validated the possibility of miR-291a-5p
      to regulate the protein expression of PDIP38. Using luciferase reporter assay,
      realtime PCR and western blot methods, we firstly demonstrated that miR-291a-5p
      directly inhibited the expression of PDIP38. The present results shed a new light
      on the study of PDIP38 and miR-291a-5p in the differentiation of ES cells.

PMID- 21090115
TI  - [Construction, expression, purification and characterization of mutant of
      Aspergillus flavus urate oxidase].
AB  - We converted the TGC codon (307-309 bp) of Aspergillus flavus urate oxidase (UOX)
      gene to a GCC codon by using fusion PCR techniques to produce a C103A mutant.
      This gene was cloned into expression vector pET-42a (+) and then transformed into
      Escherichia coli BL21 (DE3). The mutant protein (UOX-Ala103) was expressed in
      soluble form at high levels after induction with IPTG The expressed rUOX-Ala103
      accounted for about 45% of total bacterial proteins, rUOX-Ala103 of up to 98%
      purity was obtained after purified using hydrophobic interaction and anion
      exchange. Western blotting showed that the anti-UOX antibody specifically
      recognized rUOX-Ala103. The mutant protein showed a 60% increased in vitro
      biological activities compared with native protein, and performed a good activity
      of degrading the uric acid in vivo.

PMID- 21090116
TI  - [In vitro transgenic expression efficacy of a helper-dependent adenoviral vector
      encoding enhanced green fluorescent protein].
AB  - To investigate the transgenic expressing efficacy of helper-dependent adenoviral
      vector (HDAd) in vitro, we constructed a HDAd encoding enhanced green fluorescent
      protein (EGFP), denominated as HDAd/EGFP, performed large scale preparation and
      purification, and then identified the purified HDAd/EGFP under fluorescent
      microscope and electron microscope. After the concentration of HDAd/EGFP was
      determined by spectrophotometer, the transgenic expression efficiency of
      HDAd/EGFP was compared with first generation adenoviral vector encoding EGFP
      (FGAd/EGFP) in vitro. Therefore, we infected A549 cells with 2000 virus particles
      (vp) per cell by HDAd/EGFP and FGAd/EGFP respectively and analyzed EGFP
      expressing level by flow cytometry. Consequently, the fluorescent expression rate
      and fluorescent intensity of EGFP were higher in early infected A549 cells by
      HDAd/EGFP than by FGAd/EGFP. HDAd, capable of expressing transgene instantly and
      efficiently in vitro, is a potential vaccine vector.

PMID- 21090117
TI  - [Serum-free medium for suspension culture of recombinant Chinese hamster ovary
      (11G-S) cells].
AB  - With suspension adapted recombinant Chinese hamster ovary (CHO) cell lines 11G-S
      expressing human pro-urokinase (pro-UK) as the object of study, a serum-free
      medium for the cultivation of recombinant CHO cells in suspension was formulated
      by using Plackett-Burman design and response surface methodology. The two-level
      Plackett-Burman design was used to evaluate the effect of 10 medium supplements
      on the growth of the 11G-S cells in suspension culture. Among the 10 medium
      supplements, insulin, transferrin, and putrescine were identified as the most
      significant factors (P < 0.05). The response surface methodology with three
      factors and three levels was used to determine the optimal levels of these
      factors. And a serum-free medium, SFM-CHO-S for recombinant CHO cells suspension
      culture was formulated. The maximum cell density of 11G-S cells in SFM-CHO-S in
      suspension batch culture reached 4.12 x 10(6) cells/mL with a maximum pro-UK
      activity at 5614 IU/mL, which was superior to the commercial serum-free medium
      for recombinant CHO cells.

PMID- 21090118
TI  - [Characterization and culture of isolated primary dairy goat mammary gland
      epithelial cells].
AB  - Based on the in vitro culturing system developed for epithelial cells in mammary
      gland of Xinong Saanen dairy goats using tissue explant culture, high density
      cultivation, and continuous passaging, the cultured epithelial cells were
      evaluated by growth curve fitting, karyotype analysis, immunofluorescence
      staining (keratin, epithelial membrane antigen (EMA), vimentin, beta-casein), oil
      red staining and RT-PCR of beta-casein gene. The results showed that the growth
      of epithelial cells with the model number of chromosome of 60 demonstrated a
      typical 'S' shape curve, the positive gene expression of keratin, EMA, vimentin
      and beta-casein was detected, the cytoplasmic lipid droplets were observed
      following the oil red staining, the cultured cells expressed the mRNA of beta
      casein. In conclusion, the current in vitro culturing system can obtain the
      normal mammary gland epithelial cells with the function of secretion.

PMID- 21090119
TI  - [Fusion expression of fibrinolytic enzyme gene PPFE-I from endophytic
      Paenibacillus polymyxa in Escherichia coli and activity analysis].
AB  - With the genomic DNA of strain EJS-3 as the template, we amplified the gene of
      fibrinolytic enzyme from Paenibacillus polymyxa (PPFE-I) by PCR. We purified the
      PCR product and ligated it into pMD19-T. After DNA sequencing, we cloned the PPFE
      I gene into expression vector pET-DsbA and transformed it into Escherichia coli
      BL21(DE3). Upon induction of IPTG, we found that the activity of recombinant
      fibrinolytic enzyme fused with DsbA expressed in Escherichia coli was 228 IU/mL.
      SDS-PAGE analysis showed that the recombinant enzyme was soluble and accounted
      for about 18.4% of total cell protein. Western blotting demonstrated that the
      recombinant protein was DsbA-PPFE-I. We purified the recombinant enzyme by Ni
      affinity chromatography, thrombin digestion and sephadex G-100 gel-filtration,
      and identified the molecular weight of purified product to be 66.3 kDa with MALDI
      TOF mass spectrometry. The purified enzyme exhibited distinct fibrinolytic
      activity on fibrin plate.

PMID- 21090120
TI  - [Membrane transfer-based colorimetric DNA detection using enzyme modified gold
      nanoparticles].
AB  - We report here a novel membrane transfer-based DNA detection method, in which
      alkaline phosphatase labeled gold nanoparticle (AuNP) probes were used as a means
      to amplify the detection signal. In this method, the capture probe P1,
      complimentary to the 3' end of target DNA, was immobilized on the chip. The multi
      component AuNP probes were prepared by co-coating AuNPs with the detecting probe
      P2, complimentary to the 5' end of target DNA, and two biotin-labeled signal
      probes (T10 and T40) with different lengths. In the presence of target DNA, DNA
      hybridization led to the attachment of AuNPs on the chip surface where specific
      DNA sequences were located in a "sandwich" format. Alkaline phosphatase was then
      introduced to the surface via biotine-streptavidin interaction. By using BCIP/NBT
      alkaline phosphatase color development kit, a colorimetric DNA detection was
      achieved through membrane transfer. The signal on the membrane was then detected
      by the naked eye or an ordinary optical scanner. The method provided a detection
      of limit of 1 pmol/L for synthesized target DNA and 0.23 pmol/L for PCR products
      of Mycobacterium tuberculosis 16S rDNA when the ratio of probes used was 9:1:1
      (T10:T40:P2). The method described here has many desirable advantages including
      high sensitivity, simple operation, and no need of sophisticated equipment. The
      method can be potentially used for reliable biosensings.

PMID- 21090121
TI  - [Effect of trehalose on the freeze-dried boar spermatozoa].
AB  - After freeze-drying, the ultrastructure of boar sperms was observed by optical
      and electron microscopy. The in vitro development ability of the sperm was also
      examined with intracytoplasmic sperm injection (ICSI). The rate of male
      pronuclear formation was (68.52%), for cleavage (59.17%) and for blastocyst
      formation (19.16%) of the trehalose group (0.2 mol/L), significantly higher than
      those of the 50 mmol/L EDTA group (64.59%, 56.26% and 15.62%) and the control
      group (35.36%, 52.33% and 8.60%) (P < 0.05). After storage for 60, 120 and 180 d
      at 4 degrees C, no significant difference in the in vitro development was
      observed (P > 0.05). The male pronuclear, cleavage and blastocyst formation after
      ICSI with freeze-dried spermatozoa incubated for 1 h was superior than those
      incubated for 2 h (P < 0.05). No significant differences in the structures after
      stored at 4 degrees C or -20 degrees C (P > 0.05) were observed between the
      trehalose group and EDTA group. The percent of B grade freeze-dried boar
      spermatozoa in the trehalose group was higher than that of the EDTA group (P <
      0.05). Based on the ultrastructure observation, main cryogenic damage in freeze
      dried boar spermatozoa was swelling, damage or rupture in the sperm acrosome,
      neck and tail.

PMID- 21090122
TI  - [Chemiluminescent immunoassay for high-sensitivity C-reactive protein].
AB  - We developed a high-sensitivity C-reactive protein quantifiable chemiluminescent
      immunoassay (hs-CRP CLIA). The high-purity native CRP was purified from hepatic
      cirrhosis patient ascetic fluid by affinity and ion exchange chromatography and
      used as an immunogen to develop the monoclonal antibodies (mAbs) against CRP.
      Twenty-two mAbs were identified reactive with CRP in ELISA and 13 of them were
      reactive in the phosphorycholine ligand capture ELISA. The mAbs 10C5 and 10C11
      were selected to develop the hs-CRP CLIA. The linearity and performance of the hs
      CRP CLIA was characterized. It was showed not reactive when testing against other
      serum materials (IgG, hemoglobin and triglyceride). The reliable correlation (R2
      > 0.993) was obtained between testing value (RLU/S) and the concentration of
      human serum CRP calibrator. The linearity fell in the range of 0.04-20.38 mg/L.
      The assay has good accuracy and reproducibility, the mean recovery was 99% and
      the precision of the intra- and inter assay was CVs (4.2%-5.8%) and (9.0%-11.5%),
      respectively. In testing of 90 human sera, this assay performed well and
      correlated comparably with a commercial hs-CRP ELISA kit. Thus, hs-CRP CLIA is an
      accurate, reliable, quantifiable assay for detection of high-sensitive C-reactive
      protein in serum, it may be useful to improve the risk assessment of
      cardiovascular disease and the prognosis of inflammatory bowel disease.

PMID- 21090123
TI  - [Chromatography-assisted refolding of a fusion protein containing multiple
      disulfide bonds].
AB  - To establish a refolding process for the protein fused with 12-peptide of hirudin
      and reteplase (HV12p-rPA), we developed an anion-exchange chromatography assisted
      method to form correct disulfide bonds. After evaluating various parameters by
      orthogonal experiments with Q Sepharose XL as refolding medium, we found that
      urea gradient, sample loading size and L-Arg concentration were three major
      factors to affect the refolding outcomes, and urea gradient was critical to the
      recovery yield. Meanwhile, enzymatic activity of the refolded protein was
      decreased by the increase of sample loading size, and the optimal concentration
      of L-Arg in the eluting buffer was 1 mol/L. Thus, a dual-gradient of urea and pH
      on the anion-exchange chromatography resulted in remarkable increase of specific
      fibrinolytic and anti-coagulative activities of the refolded protein. Compared
      with the dilution method for refolding HV12p-rPA, the present approach was more
      effective and advantageous.

PMID- 21090124
TI  - [Analytical quality in biological monitoring of workers exposed to chemicals:
      experience of the Prevention and Safety at the Workplace Service in Modena].
AB  - BACKGROUND: The quality of laboratory data is one of the main factors in
      guaranteeing efficacy of biological monitoring. OBJECTIVES: To analyze the
      quality of laboratory data used for biological monitoring of exposed workers.
      METHODS: A survey involving 18 companies employing 945 workers in the area of
      Modena, Italy, was carried out in 2008. RESULTS: Most of the 9 private
      laboratories receiving biological samples did not perform directly part or all of
      the laboratory assessments requested, but this was not indicated in the final
      report. Major problems were observed in the application of internal quality
      control, and only one laboratory participated in external quality assessment for
      blood lead measurements. CONCLUSIONS: Our results raise major concerns on the
      traceability and reliability of laboratory assessments performed for
      biomonitoring of exposed workers. Systematic evaluation of the quality of
      analytical data would be highly recommendable.

PMID- 21090125
TI  - [The surveillance of occupational risks. Problems and perspectives of the recent
      legislative framework after the national preliminary survey].
AB  - BACKGROUND: Legislation in Italy concerning health, safety and prevention at the
      workplace recently established a new data communication standard OBJECTIVES: The
      findings are reported of a specific survey on 18 Local Health Units (ASL) over
      the entire Italian territory, aimed at identifying the critical points in data
      management and analyze the available information. METHODS: The occupational
      health physician for each company must collect and transmit information on the
      number of workers submitted to health surveillance protocols to the Local Health
      Unit. Information must be divided by risk factor and gender Local health Units
      then transmit the data to the Regions and finally to the Italian National
      Institute for Occupational Safety and Prevention (ISPESL). RESULTS: A sample of
      22.977 companies was studied, providing information on about 410,009 workers
      undergoing health surveillance protocols. Carrying or moving heavy loads,
      exposure to noise, VDU and chemical substances were the most frequent risk
      factors. The difference between genders was significant in risk allocation, with
      exposures to VDU and biological agents prevalently among females. CONCLUSIONS:
      The information thus collected suffered from a lack of data organization and
      completeness in the sample under study, but nevertheless provides preliminary
      evidence of a map of occupational risks on a national basis, confirming the
      potential for the new law (D.Lgs 81/2008) to investigate health safety and
      prevention at the workplace.

PMID- 21090126
TI  - [Epidemiological study of UL-WMSDs in 2022 VDU workers].
AB  - BACKGROUND: The literature dealing with the health effects of VDU work identified
      right from the beginning a group of MSDs, mainly affecting the cervicobrachial
      region, so that VDU work could be considered a risk factor due to biomechanical
      overload of the upper limbs, OBJECTIVES: The aim of the study was to assess the
      prevalence of symptoms and diseases of VDU workers. METHODS: A cohort of 2022
      workers (1125 males and 897 females) working at VDUs for a duration of time equal
      to or exceeding 20 hours per week, including insurance and bank employees (no
      desk activity), was submitted to clinical and functional assessment of the
      cervical spine and upper limbs following a structured protocol (case history,
      clinical and instrumental examinations), as used by occupational physicians, in
      order to identify "anamnestic cases" and diagnose upper limb biomechanical
      overload diseases. Besides medical data, a series of data was also collected in
      order to obtain details of the work task: time schedule, duration of VDU use,
      organizational autonomy, data entry method. RESULTS: The prevalence of subjects
      with UL-WMSDs was 1.9% for males and 5.8% for females, and basically similar to
      that found in non-exposed working populations. However, there did seem to be a
      correlation between cervical disorders and computer use, only for females.
      CONCLUSIONS: In the sample studied no association was shown between VDU work and
      onset of upper limb diseases, which was confirmed even considering the different
      exposure variables. Analysis of"anamnestic cases" made by comparison with non
      exposed populations, confirmed the lack of association between upper limb
      diseases and VDU work.

PMID- 21090127
TI  - [Electrocardiogram changes in shift workers].
AB  - BACKGROUND: Besides a significant deterioration in their family and personal
      life, shift workers also suffer health problems ranging from chronic fatigue to
      gastro-intestinal disorders, changes in sleep rhythm and cardiovascular disease,
      including arrhythmia and ischaemic heart disease. OBJECTIVES: The aim of the
      study was to assess the prevalence of electrocardiographic changes, such as
      conduction disorders, alterations in the repolarization phase and frequency
      adjusted QT interval (QTc) in relation to shift work. METHODS: We conducted a
      cross sectional survey of 125 male subjects, 60 of whom worked fixed hours, and
      65 were shift workers on two different schedules: 32 were on duty for 24 hours
      followed by 96 hours rest, and 33 worked 8-hour shifts (3 x 8). During periodical
      health assessment we examined their electrocardiograms (ECG), classified the
      morphology and measured the QTc interval. RESULTS: The QTc interval did not
      differ by type of work shift or by the presence of morphological changes in the
      ECG, including concurrent conduction disorders, or alterations in the
      repolarization phase. However, unlike day workers and 24-h shift workers, the QTc
      interval tended to increase with age among 8-h shift workers (r = 0.338; p =
      0.05). Also, risk of conduction disorders was moderately, but not significantly,
      elevated among 8-h shift workers compared with subjects working fixed hours (OR =
      1.9; I.E 95% 0.6, 5.7). CONCLUSIONS: Our study did not reveal significant changes
      in the ECG morphology in relation to the type of work shift.

PMID- 21090128
TI  - [Filtering facepieces: effect of oily aerosol load on penetration through the
      filtering material].
AB  - BACKGROUND: Electrostatic filters are widely used in applications requiring high
      filtration efficiency and low pressure drop. However various studies showed that
      the penetration through electrostatic filters increases during exposure to an
      aerosol flow. OBJECTIVES: This study investigates the effects of prolonged
      exposure to an oily aerosol on the penetration through filtering facepieces
      available on the market. METHODS: Some samples of FFP1, FFP2 and FFP3 filtering
      facepieces were exposed for 8 hours consecutively to a paraffin oil polydisperse
      aerosol. At the end of the exposure about 830 mg of paraffin oil were deposited
      in the facepiece. RESULTS: All the examined facepieces showed penetration values
      that increased with paraffin oil load while pressure drop values were
      substantially the same before and after exposure. The measured maximum
      penetration values did not exceed the maximum penetration values allowed by the
      European technical standards, except in one case. According to the literature,
      830 mg of oil load in a facepiece is not feasible in workplaces over an eight-
      hour shift. However, the trend of the penetration versus exposure mass suggests
      that if the load increases, the penetration may exceed the maximum allowed
      values. For comparison a mechanical filter was also studied. This showed an
      initial pressure drop higher than FFP2 filtering facepieces characterized by
      comparable penetration values. During exposure the pressure drop virtually
      doubled while penetration did not change. CONCLUSIONS: The increase in
      penetration with no increase in pressure drop in the analyzed facepieces
      indicates that it is necessary to comply with the information supplied by the
      manufacturer that restricts their use to a single shift.

PMID- 21090129
TI  - [Pier Luigi Viola and vinyl chloride: notes that were never published].
AB  - The name and work of Pier Luigi Viola (1917-1985) are unequivocally connected
      with the history of the discovery of the toxic effects of vinyl chloride, cancer
      in particular. A biography and a bibliography of Professor Viola are still
      lacking but his work is well documented; equally well known is his professional
      career as an occupational physician who spent his entire working life as an
      employee of one single industrial group, Solvay; his work was dedicated firstly
      to taking care of the health of the workers of the Corporation and not only in
      Italy, and secondly to organizing the occupational health departments of all
      Solvay's establishments in Italy. This positive connection between occupational
      physician and scientist has recently been challenged in certain historical
      reconstructions of the discovery of vinyl chloride's carcinogenicity: in
      particular, these reconstructions (which we do not consider to be coherent with
      the facts) depict Viola as in constant conflict with his employer. As crucial
      support to this view are offered on the one hand a statement by Viola, in 1980,
      that "At the basis of every discovery there is frequently the poetical
      imagination of a researcher who is always alone in facing the difficulties of the
      research, difficulties that rise up against him like a wall reaching up to the
      sky"; and on the other the supposed failure to find some of Professor Viola's
      notes which should reflect his spiritual testimony, and from which should emerge
      "the suffering, the torments, and the pressures of that initial period". The true
      history is very different: the notes do exist: they were personally delivered to
      one of the authors (PB) by Viola's widow a few months after his death; they are
      in fact the first pages of a planned book on vinyl chloride that Viola never
      actually succeeded in writing. In these pages Viola developed some personal
      reflections from which it is clear that he was conscious of having been in the
      centre ofa fantastic adventure in the field of scientific research in which he
      also played the principal role; there is no mention whatsoever of any conflict or
      contrast between Viola and Solvay. In fact, the backdrop to this story reflects
      the typical dynamics of scientific research. The article continues with the
      publication of Viola's handwritten notes: in this way the supposed "mistery of
      the missing notes" is solved.

PMID- 21090131
TI  - [Crisis or transformation?].

PMID- 21090130
TI  - [Art. 40 d.lgs 81/80, relations of the competent physician with the National
      Health Service for a new model of health prevention at work: first results of the
      analysis of the data of the 3B addendum].

PMID- 21090132
TI  - [Fever and hyperthermia].
AB  - The knowledge of the physiological mechanisms for controlling body temperature,
      and the etiology and pathophysiology of fever and hyperthermia nursing care
      enable these interdisciplinary problems, allowing early detection to prevent its
      progression. It also allows the nurse the implementation of quality care through
      the adoption of specific measures to lower the temperature, the administration of
      medical therapy, hemodynamic monitoring, respiratory and metabolic control and
      water.

PMID- 21090133
TI  - [Fibromyalgia: beyond the depression].
AB  - INTRODUCTION: Depression has several ways to manifest: affective disorders,
      cognitive, sleep disturbance, difficulty in sexuality, appetite changes,
      behavioral changes, pain, paresthesia, headache, dizziness, gastrointestinal,
      cardiovascular, respiratory, neurovegetative etc. Can fibromyalgia be another way
      to manifest depression? Or would we be talking about a higher degree of injury to
      the body that is manifested in this way because of the depression continued
      throughout life as a result of difficulties experienced by women? Is what we
      identify as beyond depression. OBJECTIVE: To determine the causes of women who
      attributed the cause of fibromyalgia. Compare the current level of anxiety and
      depression, perceived health status of the group of women diagnosed with
      depression and those diagnosed with fibromyalgia. MATERIALS AND METHODS: in-depth
      interviews with 20 women with fibromyalgia, 52 women with depression in primary
      care. Systematic sampling in different age groups in different clusters-quota
      patients with non-response replenishment. Analysis secondary sources. RESULTS:
      Women with fibromyalgia have increased work and family stress, perceived
      violence, perceived difficulties in childhood that women are only diagnosed
      depression. They also have a lower perception of their health. CONCLUSION: Women
      diagnosed with fibromyalgia have made enormous psychosocial difficulties
      throughout their lives that have been identified as causative factors. The most
      important thing is that the society and physicians understand the disease.

PMID- 21090134
TI  - [Accidents in the home. Acute intoxication by household products].
AB  - During a two month period, the authors gathered data from patients who visited an
      emergency ward due to acute intoxication by a household product, and they
      compared the care which those patients required with the other patients suffering
      from different intoxications. The variables were introduced and analyzed using a
      SPSS 75.0 statistics package. The emergency ward registered 281 intoxication
      incidents of which 22 or 8.7% were related to household products. Among the
      conclusions drawn from this study the authors emphasize that the majority of
      patients intoxicated by household products were women. Caustic products are
      involved in the greatest number of incidences, either accidentally swallowed,
      splashed into eyes or inhaled as gas. The amount of treatment those patients
      require is less than the treatment required for other intoxications. Their
      prognostic is good.

PMID- 21090135
TI  - [Macular degeneration associated with age. All that is essential to know].
AB  - Patients usually have many questions regarding what macular degeneration is. In
      this article, the author lists the most frequent questions and the answers which
      nursing professionals should provide.

PMID- 21090136
TI  - [The pharmacokinetic process: is the drug getting to its site of action?: Drug
      distribution (ADME)].
AB  - Many drugs are bound to circulating proteins, usually albumin (acidic drugs), but
      also globulins (hormones), lipoproteins (basic drugs), and acid glycoproteins
      (basic drugs). Only the fraction of drug that is not protein-bound can bind to
      cellular receptors, pass across tissue membranes, and gain access to cellular
      enzymes, thus being distributed to body tissues, metabolized, and excreted (for
      example by the kidney). Changes in protein binding can therefore sometimes cause
      changes in drug distribution. For such changes to be important, the bound drug
      must constitute more than 90% of the total drug in the plasma and possess a
      reduced therapeutic window Besides this, the extent of distribution of the drug
      to the tissues must be small (less than 0.15 L/kg). This is because if the drug
      is widely distributed to the body tissues, then even large increases in the
      amount of unbound drug in the plasma will be unimportant.

PMID- 21090137
TI  - [Acute infantile diarrhea. Nursing treatment].
AB  - Acute diarrhea is a common cause of sickness and hospitalization of children
      throughout the world. Handling children who have acute gastroenteritis includes
      the use of oral rehydration solutions combined with a timely reintroduction to a
      complete regular diet, which satisfies the energy and nutritional requirements
      according to the age and nutritional history of the patient under care. Children
      who suffer severe diarrheas might require hospitalization, but the majority of
      these cases can be treated in outpatient clinics or at home. For very few cases
      it is necessary to resort to the use of intravenous serum therapy. Parents should
      be aware of the risks which gastroenteritis poses for their children, and be
      familiar with the use of oral rehydration solutions. These solutions should be
      kept on hand in all homes which have children in them. Nursing personnel's role
      in teaching parents about how to deal with acute diarrhea or gastroenteritis van
      be the key to prevention and precocious, timely treatment of complications due to
      acute diarrhea in children.

PMID- 21090138
TI  - [Nursing care for the patient with diabetic foot].

PMID- 21090139
TI  - Medicare: how to navigate the maze.

PMID- 21090140
TI  - Shopping for eyeglasses: for cost and quality, Costco excels.

PMID- 21090141
TI  - A strategy for healthy aging in Massachusetts: synthesis of steering committee
      meetings and progress.

PMID- 21090142
TI  - Medicaid program; withdrawal of determination of average manufacturer prices,
      multiple source drug definition, and upper limits for multiple source drugs.
      Final rule.
AB  - This final rule withdraws two provisions from the "Medicaid Program; Prescription
      Drugs'' final rule (referred to hereafter as "AMP final rule") published in the
      July 17, 2007 Federal Register. The provisions we are withdrawing are as follows:
      The determination of average manufacturer price, and the Federal upper limits for
      multiple source drugs. We are also withdrawing the definition of "multiple source
      drug" as it was revised in the ''Medicaid Program; Multiple Source Drug
      Definition'' final rule published in the October 7, 2008 Federal Register.

PMID- 21090143
TI  - Responding to disruptive patients. Final rule.
AB  - This final rule amends the Department of Veterans Affairs (VA) regulation that
      authorizes appropriate action when a patient engages in disruptive behavior at a
      VA medical facility. This amendment updates VA's current regulation to reflect
      modern medical care and ethical practices. The final rule authorizes VA to modify
      the time, place, and/or manner in which VA provides treatment to a patient, in
      order to ensure the safety of others at VA medical facilities, and to prevent any
      interference with the provision of medical care.

PMID- 21090144
TI  - Medical devices; general and plastic surgery devices; classification of non
      powered suction apparatus device intended for negative pressure wound therapy.
      Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the non-powered suction
      apparatus device intended for negative pressure wound therapy (NPWT) into class
      II (special controls). The special control that will apply to the device is the
      guidance document entitled "Class II Special Controls Guidance Document: Non
      Powered Suction Apparatus Device Intended for Negative Pressure Wound Therapy."
      The agency is classifying the device into class II (special controls) in order to
      provide a reasonable assurance of safety and effectiveness of the device.
      Elsewhere in this issue of the Federal Register, FDA is publishing a notice of
      availability for the guidance document entitled "Class II Special Controls
      Guidance Document: Non-Powered Suction Apparatus Device Intended for Negative
      Pressure Wound Therapy."

PMID- 21090145
TI  - Amendment to the interim final rules for group health plans and health insurance
      coverage relating to status as a grandfathered health plan under the Patient
      Protection and Affordable Care Act. Amendment to interim final rules with request
      for comments.
AB  - This document contains an amendment to interim final regulations implementing the
      rules for group health plans and health insurance coverage in the group and
      individual markets under provisions of the Patient Protection and Affordable Care
      Act regarding status as a grandfathered health plan; the amendment permits
      certain changes in policies, certificates, or contracts of insurance without loss
      of grandfathered status.

PMID- 21090146
TI  - Medicare program; home health prospective payment system rate update for calendar
      year 2011; changes in certification requirements for home health agencies and
      hospices. Final rule.
AB  - This final rule sets forth an update to the Home Health Prospective Payment
      System (HH PPS) rates, including: the national standardized 60-day episode rates,
      the national per-visit rates, the nonroutine medical supply (NRS) conversion
      factors, and the low utilization payment amount (LUPA) add-on payment amounts,
      under the Medicare prospective payment system for HHAs effective January 1, 2011.
      This rule also updates the wage index used under the HH PPS and, in accordance
      with the Patient Protection and Affordable Care Act of 2010 (Affordable Care
      Act), updates the HH PPS outlier policy. In addition, this rule revises the home
      health agency (HHA) capitalization requirements. This rule further adds
      clarifying language to the "skilled services" section. The rule finalizes a 3.79
      percent reduction to rates for CY 2011 to account for changes in case-mix, which
      are unrelated to real changes in patient acuity. Finally, this rule incorporates
      new legislative requirements regarding face-to-face encounters with providers
      related to home health and hospice care.

PMID- 21090147
TI  - Medicare and Medicaid programs: changes to the hospital and critical access
      hospital conditions of participation to ensure visitation rights for all
      patients. Final rule.
AB  - This final rule will revise the Medicare conditions of participation for
      hospitals and critical access hospitals (CAHs) to provide visitation rights to
      Medicare and Medicaid patients. Specifically, Medicare- and Medicaid
      participating hospitals and CAHs will be required to have written policies and
      procedures regarding the visitation rights of patients, including those setting
      forth any clinically necessary or reasonable restriction or limitation that the
      hospital or CAH may need to place on such rights as well as the reasons for the
      clinical restriction or limitation.

PMID- 21090148
TI  - Expression of concern: Prevention of central venous line-related thrombosis by
      continuous infusion of low-dose unfractionated heparin, in patients with haemato
      oncological disease. A randomized controlled trial.

PMID- 21090149
TI  - AAFP reaches out with feline health information.

PMID- 21090150
TI  - High prevalence of EEE in Michigan.

PMID- 21090151
TI  - Deadly pneumonia traced to domestic sheep.

PMID- 21090152
TI  - FDA considering approval of genetically engineered salmon.

PMID- 21090153
TI  - Questions conclusions in study of blood pressure measurement system.

PMID- 21090154
TI  - Thoughts on the threat of Ehrlichia ruminantium infection.

PMID- 21090155
TI  - An experience in removal of a foreign body from the trachea.

PMID- 21090156
TI  - Computational fluid dynamics analysis of nasal flow.
AB  - OBJECTIVES: Standard methods to examine nasal flow are experimental and do not
      yield locally detailed results. Using the Lattice-Boltzmann method (LBM), we
      computed nasal air flow and investigated the relationship between nasal
      obstruction and anatomical conditions. Because of its mathematical structure, the
      LBM can be immediately applied to various nasal cavities that are characterized
      by an extremely intricate geometry. In the present study, the higher efficiency
      of the LBM allowed for high resolution and detailed analysis of the flow
      structures in the nasal cavity. METHODOLOGY: Based on a previously validated
      simulation of nasal airflow in an artificial model, we acquired the nasal
      geometry of an individual by computed tomography and applied the LBM to
      numerically solve Navier-Stokes equations and thereby determine nasal flow.
      RESULTS: In contrast to frequently used standard finite-volume methods, our
      method facilitated grid generation and computational parallelisation. The grid
      modelling of the nasal cavity comprised 4.9 million nodes and the computational
      time on a high-performance computing cluster was less than 12 hours. The velocity
      and pressure of the calculated airflow was visualized in every tiny recess of the
      nasal cavity and areas of interest could be easily identified. CONCLUSION:
      Computer-assisted visualization of patients' 3D nasal flow structures may be
      useful for diagnosis, and for planning surgical interventions. Although numerical
      analysis is far from real-time, and the generation of geometric models still
      requires a large amount of manual interaction, our simulation approach will be
      useful for nasal flow research.

PMID- 21090157
TI  - Prevalence of sphenoid sinus agenesis in adults: a CT scan study.
AB  - OBJECTIVE: Sphenoid sinus agenesis is a very rare entity. In this study, we
      evaluated the CT scans of 1193 patients and detected cases with sphenoid sinus
      agenesis despite the absence of craniofacial anomalies or syndromes. METHODS: The
      CT scans of 1193 patients who had undergone endoscopic sinus surgery in our
      clinic between 1999 and 2008 were retrospectively evaluated. Of the patients, 652
      (54.6%) were female and 541 (45.3%) were male. The mean age of the patients was
      32 years (range: 13-75 yrs.). RESULTS: In this study, we identified eight
      patients (0.67%) with sphenoid agenesis. Three patients (37.5%) had bilateral, 3
      patients (37.5%) had left, and 2 patients (25%) had right sphenoid agenesis. None
      of the patients had craniofacial anomalies or syndromes. CONCLUSION: Sphenoid
      sinus agenesis is rarely seen in the absence of craniofacial anomalies or
      syndromes. In our study, its incidence was 0.67%. Awareness of sphenoid sinus
      agenesis and/or hypoplasia is very important, particularly when transphenoidal
      hypophysectomy is planned.

PMID- 21090158
TI  - Is there any relationship between nCPAP therapy and signs of sinus
      hyperpneumatization?
AB  - OBJECTIVES: Both nasal continuous positive airway pressure (nCPAP) therapy and
      nose blowing can generate high pressures in the nose and sinuses. Nose blowing
      generates higher pressures than nCPAP therapy, but the duration of nCPAP therapy
      is considerably longer than the duration of nose blowing. Therefore, nCPAP could
      cause bone deformation. The aim of this study was to document the influence of
      the pressure generated by nCPAP therapy on the structure and dimensions of the
      sinuses and on the nose-blowing patterns of the patients. METHODOLOGY: The study
      included nine patients, who had recently been diagnosed with obstructive sleep
      apnea syndrome (OSAS) and had not received any previous treatment for OSAS.
      Before nCPAP therapy was started, they all underwent computer tomography (CT) in
      the prone position with sequential coronal slices followed by pressure
      measurements during nose blowing. After the initial measurements, nCPAP therapy
      commenced. All of the patients were treated with a fixed-pressure device and
      nasal mask for 6 mo. nCPAP therapy compliance was checked after 6 mo. At the end
      of the 6 mo treatment with nCPAP, coronal CT scans of the sinuses and pressure
      measurements during nose blowing were repeated. RESULTS AND CONCLUSION: Although
      CPAP therapy provides continuous positive pressure for several hours at night,
      bone structure and sinus dimensions appeared to be unchanged after 6 mo of
      therapy. However, CPAP therapy seemed to have an effect on the nose-blowing
      pattern of the patients, with a significant decrease in nose blowing pressure
      after 6 mo of CPAP treatment.

PMID- 21090159
TI  - A-mode ultrasound in the diagnosis of maxillary sinusitis in ventilated patients.
AB  - PROBLEMS/OBJECTIVES: The diagnosis of maxillary sinusitis in intensive care
      patients remains problematic. However, it is essential since maxillary sinusitis
      causes numerous complications and there is an effective treatment. The aim of
      this study was to compare A-mode ultrasound with sinus computed tomography (CT)
      for the diagnosis of maxillary sinusitis in intubated patients in critical care
      undergoing mechanical ventilation. METHODOLOGY: Prospective clinical study in 140
      maxillary sinuses in the surgical ICU of a university hospital. In each intubated
      and mechanically ventilated patient undergoing cerebral CT scan for any reason, a
      bedside A-mode ultrasonography of the maxillary sinuses was performed the same
      day. The A-mode ultrasound result was compared with the result of the sinus CT
      scan for the diagnosis of maxillary sinusitis. RESULTS: Sensitivity, specificity,
      positive predictive value and negative predictive value of A-mode ultrasound
      compared with CT were 66.7%, 94.7%, 75.0% and 92.2% respectively. All the empty
      sinuses were correctly identified as being empty. CONCLUSIONS: Given its very
      good specificity and negative predictive value, bedside A-mode ultrasound may be
      a useful first-line examination for intubated and mechanically ventilated
      patients in intensive care, especially to eliminate suspicion of maxillary
      sinusitis.

PMID- 21090161
TI  - Auditing in middle ear surgery, feasibility of the common otology database.
AB  - OBJECTIVES: Clinical auditing is a systematic process for improving quality of
      care. The primary goal is to compare current practice with established standards.
      A common dataset enables the comparison of results, and takes into account the
      effect of case mix, surgical techniques and follow-up periods on outcome. The
      Common Otology Database (COD) is a joint effort of an international group of
      otologists to standardise reporting on middle ear surgery, including
      myringoplasty, ossiculoplasty, stapes surgery and cholesteatoma removal. It aims
      to identify audit data using the internet (http://www.ear-audit.net), provide a
      storage system for otological data, to create a prospective database allowing
      statistical analysis with sufficient power and to produce standards for
      comparative auditing. MATERIALS AND METHODS: The COD provides two levels of data
      entry, anonymising surgeon and patient data. Level 1 is designed for general
      otorhinolaryngologists and trainees, and only records main outcomes. Level 2 is
      designed for benchmark otologists and includes detailed information about
      pathologies, risk factors, aim of surgery, surgical findings, procedures, follow
      up periods and complications. Level-2 surgeons are required to submit pre
      operative data on all patients scheduled for surgery in order to eliminate bias
      as a result of selective reporting. RESULTS: The COD began in January 2004 and is
      continuously including patients. In May 2009, 2,291 cases were entered in the
      level-2 benchmark database, including 1,218 myringoplasties (53.2%), 576
      ossiculoplasties (25.1%), 695 stapes surgeries (30.3%) and 532 cholesteatoma
      surgeries (23.2%). Currently, 151 surgeons use the database system (levels 1 and
      2 combined). Eighteen otologists were invited to contribute to the level 2
      database. Eight contributors complied with the validation criteria. Others did
      not cooperate, citing a lack of resources to support data input, or their health
      system discouraging follow-up. Some were also reluctant to have their outcome
      data subjected to external validation. CONCLUSION: The COD has engaged the
      otological community to participate in a large-scale audit of current practice.
      The number of surgical procedures included has attained a level of power that
      will allow introductory statistical analysis.

PMID- 21090160
TI  - Sensorineural hearing loss in ankylosing spondylitis treated with TNF blockers.
AB  - OBJECTIVES: Sensorineural hearing loss (SNHL) in the uncommon disease ankylosing
      spondylitis (AS) has been previously reported. We analysed the relationships
      between AS, anti-TNF drug treatment, and SNHL. METHODOLOGY: We determined pure
      tone thresholds in 28 consecutive patients with AS who were treated with the
      TNFalpha inhibitors etanercept or infliximab, or with a TNFalpha inhibitor plus
      methotrexate (MTX). RESULTS: SNHL was diagnosed in 16 patients (57.1%): 7/7
      (100%) of those treated with anti-TNFalpha plus MTX, and 9/21 (43%) of those
      treated with anti-TNFalpha alone. We found a significant association between SNHL
      and treatment modality (p = 0.011) or treatment time in months (p = 0.020).
      CONCLUSIONS: The SNHL rate was significantly higher in patients treated with anti
      TNFalpha plus MTX than those treated with anti-TNFalpha alone. The culpability of
      anti-TNF therapy was supported by the association between SNHL and treatment
      time, which was longer for anti-TNFalpha plus MTX than for anti-TNFalpha alone.
      SNHL may be due not only to AS, but also to drug-induced vasculitis of the
      labyrinthine artery or its cochlear branch.

PMID- 21090162
TI  - Tinnitus sound therapy with open ear canal hearing aids.
AB  - OBJECTIVE: The aims of this study were to evaluate the efficacy of open ear canal
      hearing aids in tinnitus treatment and to investigate the influence of gender,
      age, medication usage, tinnitus cause, tinnitus perception side, tinnitus pitch,
      pure tone audiometry, distortion product otoacoustic emissions, and minimal
      masking level on outcome. METHODOLOGY: One hundred tinnitus patients were
      evaluated by the tinnitus handicap inventory (THI) at the beginning of the study
      and after nine months of treatment. All subjects were submitted to counselling
      and sound enrichment from the simple sound amplification provided by the open ear
      canal hearing aids. RESULTS: Initial mean THI score was 54.22 (+/- 20.37) and
      final mean score was 28.32 (+/- 16.50), p < 0.0001. No statistically significant
      correlations were found between THI value reduction and the studied parameters.
      CONCLUSION: Open ear canal hearing aids were useful in all tinnitus patients with
      mild hearing loss.

PMID- 21090163
TI  - Keutel syndrome in a patient presenting with hearing loss.
AB  - Keutel syndrome (KS) is a rare autosomal recessive disease which is mainly
      characterised by abnormal cartilage calcification, peripheral pulmonary artery
      stenosis, sensorineural and conductive hearing loss, brachytelephalangism, and
      midface hypoplasia. Here, we present and discuss a Keutel syndrome patient with
      hearing loss born to consanguineous parents (first cousins), along with all the
      characteristic features of KS.

PMID- 21090164
TI  - Central mucoepidermoid carcinoma of the maxilla: a case report.
AB  - BACKGROUND AND OBJECTIVE: Primary mucoepidermoid carcinoma of the jaw is a rare
      lesion, comprising 2-3% of all mucoepidermoid carcinomas reported in literature.
      Central mucoepidermoid carcinoma of the maxilla is rarer, comprising only 8% of
      the mucoepidermoid carcinomas found in the jaw. METHODOLOGY: A 52-year-old man
      suffered from central mucoepidermoid carcinoma of the right maxilla with cervical
      metastasis, and underwent partial maxillectomy and neck dissection in our
      hospital. The diagnosis was confirmed by histopathology, dental
      orthopantomography, CT, and PET/CT scans. RESULT: The man was followed-up
      regularly and was disease free after 21 months. CONCLUSION: Primary central
      mucoepidermoid carcinoma of the jaw is a rare lesion and radical surgical
      resection is the preferred treatment.

PMID- 21090165
TI  - Treatment of rhinophyma with radiofrequency: a case report.
AB  - PROBLEM: Rhinophyma is characterized by a slow progressive enlargement of the
      nasal skin that cannot resolve spontaneously. Clinically, the lower two-thirds of
      the nose becomes enlarged and hypervascular, developing a reddish-purple
      discoloration and a nodular appearance. It is believed that rhinophyma represents
      the end stage of acne rosacea. The treatment modalities are medical and surgical.
      CASE: This study describes a 62-year-old man with rhinophyma that was treated
      with a radiofrequency technique. The pathological examination was compatible with
      acne rosacea. After surgery, a broad-spectrum sunscreen was applied until
      reepithelialization was complete. CONCLUSION: We recommend the radiofrequency
      technique for treatment of rhinophyma.

PMID- 21090166
TI  - A laryngocele revealing a small cell lung carcinoma.
AB  - BACKGROUND: Laryngocele is defined as an abnormal dilatation of the laryngeal
      ventricle. It is a very rare entity, and the exact underlying mechanism is still
      unclear. Laryngoceles are associated with larynx carcinoma but not yet lung
      cancer. CASE PRESENTATION: A 46-year-old man presented with stridor, wheezing,
      dyspnea at rest, hoarseness evolving over two months, and cyanosis secondary to
      cervical swelling. His medical history included a 72 pack-year smoking habit and
      chronic obstructive pulmonary disease for 10 years. Airway management included a
      surgical tracheotomy for respiratory distress. A neck CT revealed laryngocele. A
      chest X-ray showed a left basal pulmonary opacity. Bronchoscopic exploration
      found an infiltrated and narrow left stem bronchus with complete stenosis of the
      lingula. Pathology revealed a small cell lung carcinoma. CONCLUSION: Our case
      shows the possible association of laryngocele and lung carcinoma. The
      pathophysiology was explained by the long history of tobacco smoking and the
      underlying chronic obstructive pulmonary disease with chronic cough.

PMID- 21090167
TI  - Difficult airway due to protruding macroglossia in a child with lymphangioma.
AB  - Lymphangiomas, or cystic hygromas, are relatively uncommon congenital
      malformations of the lymphatic system that usually present during the first years
      of childhood. They are rare in adults. A search of the literature on MedLine
      revealed only few reports about lymphangioma as a cause of difficult airway
      management after the neonatal period. Herein, we present a case of difficult
      intubation due to protruding macroglossia in a 5-year-old girl diagnosed with
      recurrent lesions of lymphangioma. We also discuss possible problems in airway
      protection, drug choice, and post-operative follow-up associated with surgical
      excision of these lesions.

PMID- 21090168
TI  - Intracranial hemorrhage in Kimura's disease: coincidence or consequence?
AB  - OBJECTIVE: To report an unusual case of Kimura's disease associated with
      intracranial hemorrhage, the first such report in the literature. CASE REPORT: A
      38-year-old man presented with chronic neurological disorders and a 10-year
      history of left cervical soft tissue swellings. Magnetic resonance imaging (MRI)
      of the cranium showed a subacute/chronic hematoma in the left occipitotemporal
      lobe and a chronic infarct in the right parietal lobe. Cervical computed
      tomography (CT) and MRI showed multiple masses on the left side of the neck and
      parotid gland. Histopathologic examination revealed lymphocyte and eosinophil
      infiltration, proliferation of hyalinated blood vessels, and interstitial
      fibrosis. Steroid therapy (2 mg/kg per day) was started and the lesions regressed
      partially. The masses and some enlarged regional lymph nodes were resected.
      CONCLUSIONS: Intracranial hemorrhage can either be a coincidental finding or
      complication of Kimura's disease. MRI and CT are effective modalities in
      radiologic diagnosis of this condition.

PMID- 21090169
TI  - A historical vignette (19). An orbital trauma in the 16th century.
AB  - An orbital trauma in the 16th century. On 30 June 1559, during a jousting
      tournament, King Henri II of France incurred an injury to the eye from a
      shattered lance, dying ten days later. Trepanation was discussed briefly before
      being rejected. The autopsy on the King confirmed that it would have been
      justified. Even though there was no skull fracture, there was a secondary rebound
      trauma resulting in a subdural haematoma in the occipital area. This paper
      examines why the trepanation option was rejected (Figure 1).

PMID- 21090170
TI  - Isolation and characterization of stress induced Ty1-copia like retrotransposable
      elements in chickpea (Cicer arietinum L.).
AB  - Almost all active plant retroelements are known to be induced by various biotic
      and abiotic stresses. Here, we show the presence of transcriptionally active Ty1
      copia like retroelements in chickpea and their induction in response to abiotic
      stress. Eight Ty1-copia retrotransposon like mRNA sequences were reverse
      transcribed, amplified, cloned and characterized from stressed plants. These mRNA
      sequences were not detected in chickpea plants grown under normal conditions.
      Basing on the similarity analysis, these RT transcript sequences were classified
      into three families. It is proposed that all sequences except CARE7 might be
      transcript sequences of functional retrotransposons. The mRNA sequence CARE3
      shows 99% nucleotide identity to a genomic Ty1-copia like sequence present in the
      Genbank with accession no. AJ535883.

PMID- 21090171
TI  - Induction of new ADAM related proteins from treated human Chang-liver cells.
AB  - Chang-liver cells is a cell line generated from human liver tissue, which is
      often used in scientific research. ADAMs are a family of proteins that consist of
      multi-domains, possess multi-functions and play a central role in normal or
      abnormal physiological conditions, such as regeneration and tumorigenesis. To
      investigate the expression and functional alteration of the ADAMs or ADAM related
      proteins in Chang-liver cells, this cell line was treated with heat stress,
      modified Hanks solution containing ATP or other buffers. Our results showed that
      the treatment with Hanks solution containing ATP induces Chang-liver cells to
      express new ADAM related proteins. To analyze these new ADAM related proteins, a
      cDNA expression library was constructed for the treated Chang-liver cells. A
      series of positive clones were obtained through immunoscreening with an ADAMs
      common antibody. A new ADAM related protein possessing alkaline protease activity
      was confirmed in these clones.

PMID- 21090172
TI  - Developmental changes in DNA methylation of pollen mother cells of David lily
      during meiotic prophase I.
AB  - Epigenetic marks in the form of DNA methylation are involved in the development
      of germ cells and are important in the maintenance of fertility. However, the
      controlling system of the on-off switch for DNA methylation largely remains
      unclear. In this study, the extent of cytosine methylation during the meiotic
      prophase I in David lily is assessed using high pressure liquid chromatography to
      evaluate the DNA methylation rates. Comparing the degree of DNA methylation
      before, during, and after synizesis, both de novo methylation and demethylation
      occurred. Mainly the methylation level decreased by 21.3% (from 54.8 to 33.5%)
      during synizesis in the pollen mother cells. The developmental timing of genome
      wide DNA methylation acquisition during pollen mother cell development is
      clarified in this paper. The relative amounts of 5-methyl-deoxycytidine of global
      methylation in leaf DNA in David lily were also higher than in other species
      reported.

PMID- 21090174
TI  - Expression of a modified antimicrobial peptide BhSGAMP-1-S (Bradysia hygida) in
      Escherichia coli and characterization of its activity.
AB  - OBJECTIVE: Bradysia hygida salivary glands antimicrobial peptide 1 (BhSGAMP-1) is
      one of the antimicrobial peptides involved in a preventive mechanism of defense
      of the fly Bradysia hygida. To know better about the molecular characterization
      of this antimicrobial peptide, we expressed and purified the modified BhSGAMP-1-S
      and investigated its antimicrobial activity. METHODS: We synthesized the gene of
      BhSGAMP-1-S designed with preferred codons of Escherichia coli and expressed it
      as a fusion protein in E. coli TB1 by using pMAL-c2X as vector. We purified the
      fusion protein using amylase resin affinity chromatography. In addition, we
      cleaved the fusion protein by enterokinase and the released recombinant BhSGAMP-1
      S was separated by size exclusion chromatography, then followed by reversed-phase
      high performance liquid chromatography. We analyzed the antimicrobial activities
      of the purified recombinant BhSGAMP-1-S by bioassays. RESULTS: The fusion protein
      was mostly expressed in soluble form under the optimized conditions. The
      recombinant BhSGAMP-1-S was produced with a pure yield of 0.38 mg/100 mL culture
      medium. Antimicrobial assays demonstrated that the recombinant BhSGAMP-1-S was
      active against several Gram-positive and Gram-negative bacteria and fungi.
      CONCLUSION: It appears to be the first successful production of the recombinant
      BhSGAMP-1-S from fly Bradysia hygida. Data presented here confirm that the
      recombinant BhSGAMP-1-S is now ready for further studying and characterizing
      their antimicrobial properties.

PMID- 21090173
TI  - Investigation of the eIF2alpha phosphorylation mechanism in response to
      proteasome inhibition in melanoma and breast cancer cells.
AB  - The 26S proteasome is an ATP-dependent proteolytic complex found in all
      eukaryotes, archaebacteria, and some eubacteria. Inhibition of the 26S proteasome
      causes pleiotropic effects in cells, including cellular apoptosis, a fact that
      has led to the use of the 26S proteasome inhibitor, bortezomib, for treatment of
      the multiple myeloma cancer. We previously showed that in addition to the effects
      of proteolysis, inhibition of the 26S proteasome causes a rapid decrease in the
      protein synthesis rate due to phosphorylating alfa subunit of the eukaryotic
      translation initiation factor 2 (eIF2alpha) by the heme-regulated inhibitor
      kinase (HRI). In order to test whether inhibition of the 26S proteasome causes
      the same effect in cancer cells, we have investigated the influence of two
      commonly used proteasome inhibitors, bortezomib and MG132, on the phosphorylation
      status of eIF2alpha in B16F10 melanoma and 4T1 breast cancer cells. It was found
      that both of the inhibitors caused rapid phosphorylation of eIF2alpha. Taking
      into account that the Hsp70 is a critical component needed for the HRI activation
      and enzymatic activity, we have tested a possible participation of this protein
      in the eIF2alpha phosphorylation event. However, treatment of the cells with two
      structurally different Hsp70 inhibitors, quercetin and KNK437, in the presence of
      the proteasome inhibitors did not affect the eIF2alpha phosphorylation. In
      addition, neither protein kinase C (PKC) nor p38 mitogen-activated protein kinase
      (MAPK) was required for the proteasome inhibitor-induced eIF2alpha
      phosphorylation; futhermore, both the PKC inhibitor staurosporine and the p38
      MAPK inhibitor SB203580 caused enchanced phosphorylation of eLF2alpha. Zinc (II)
      protoporphyrine IX (ZnPP), an inhibitor of the heme-oxygenase-1 (HO-1), which has
      also been previously reported to be involved in HRI activation, also failed to
      prevent the induction of eIF2alpha phosphorylation in the presence of the
      proteasome inhibitor bortezomib or MG132.

PMID- 21090175
TI  - Risk factors associated with hemoglobin levels and nutritional status among
      Brazilian children attending daycare centers in Sao Paulo City, Brazil.
AB  - Like many other developing countries, Brazil has been going a nutritional
      transition which presence both malnutrition and overweight. Stunting and
      overweight are the major public health problems in Brazilian children. The
      objective of this study was to document the prevalence of stunting, overweight
      and anemia in preschool children and examine if those nutritional problems are
      related; also identify if these nutritional problems have the same risk factors.
      Data from the "Efficient Daycare Center Project" which include 270 children
      attending nurseries of eight daycare centers in Sao Paulo city, Brazil were used
      for this study. Data on height and weight were converted to z-scores using WHO
      anthro software. Hemoglobin (Hb) concentrations were determined on finger-prick
      blood samples. The co-occurrence of stunting, overweight and anemia was
      investigated by contingency tables a log-linear model. Univariate and multiple
      regression analyses were performed to estimate the association of HAZ, WAZ, WHZ
      and Hb levels with their risk factors. The results showed high prevalence of
      overweight (22.2%), risk of stunting (22.6%) and anemia (37%). Percent of daycare
      attendance, age, number of siblings under 5 years old and per capita income are
      associated with Hb levels. This study provides evidence that Brazil is going
      through a nutritional transition and suggest that the adoption of public policies
      to expand and improve services in daycare centers may help to prevent multi
      nutritional problems in preschool children.

PMID- 21090176
TI  - Factors associated with household food security of participants of the MANA food
      supplement program in Colombia.
AB  - The objective of this study was to explore demographic and economic
      characteristics associated with household food security of 2,784 low-income
      households with pre-school aged children receiving food supplements from the
      Colombian Plan for Improving Food and Nutrition in Antioquia - MANA (Mejoramiento
      Alimentario y Nutricional de Antioquia) in the Department of Antioquia, Colombia.
      Included in the study was a 12-item household food security survey was collected
      from a cross-sectional, stratified random sample of MANA participants in which
      households were characterized as food secure, mildly food insecure, moderately
      food insecure, and severely food insecure. It was hypothesized that household
      food security status would be strongly associated with demographic
      characteristics, food expenditure variables, and food supplement consumption by
      children in MANA. Food insecure households were characterized by more members,
      older parents, and lower income (p < 0.0001). Rural residence and female head of
      households had higher rates of food insecurity (p < 0.01). Food insecure
      households had the lowest monthly expenditures food (p < 0.0001). Severely food
      insecure households saved the highest percentage of per capita food expenditure
      from consuming MANA supplements (p < 0.0001), similarly, MANA food supplement
      intakes were greatest in households reporting the most food insecurity (p <
      0.001). The results of this study are important to describe characteristics of
      the population benefiting from the MANA nutrition intervention by their unique
      level of household food security status.

PMID- 21090177
TI  - Carotenoid composition and antioxidant activity of the raw and boiled fruit
      mesocarp of six varieties of Bactris gasipaes.
AB  - Total carotenoid content and composition of carotenoids of six varieties of
      Bactris gasipaes were determined by spectrophotometry and HPLC, with photodiode
      array detector. Significant differences in total carotenoid content (1.1 to 22.3
      mg/100g) were detected among these varieties. Boiling the fruits for 30 minutes
      did not affect total carotenoid content, but did change the amount of some
      specific carotenoids, mainly by the production of Z-isomers. Peach palm varieties
      had the same carotenoids, but in different proportions, presenting mainly, all E
      beta-carotene (26.2% to 47.9%), Z-gamma-carotene (18.2% to 34.3%) and Z-lycopene
      (10.2% to 26.8%). When antioxidant activity was evaluated using DPPH, it was
      observed that the variety with higher percentages of beta-carotene (54.1%)
      presented the higher activity. This is one of the first reports in carotenoid
      content and antioxidant activity in well typified varieties of Bactris gasipaes,
      whose results could have a positive impact in the consumption of certain peach
      palm varieties.

PMID- 21090178
TI  - Australia's notifiable disease status, 2008: annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2008, 65 communicable diseases and conditions were nationally notifiable in
      Australia. States and territories reported a total of 160,508 notifications of
      communicable diseases to the National Notifiable Diseases Surveillance System, an
      increase of 9% on the number of notifications in 2007. In 2008, the most
      frequently notified diseases were sexually transmissible infections (69,459
      notifications, 43% of total notifications), vaccine preventable diseases (34,225
      notifications, 21% of total notifications) and gastrointestinal diseases (27,308
      notifications, 17% of total notifications). There were 18,207 notifications of
      bloodborne diseases; 8,876 notifications of vectorborne diseases; 1,796
      notifications of other bacterial infections; 633 notifications of zoonoses and 4
      notifications of quarantinable diseases.

PMID- 21090179
TI  - Arboviral diseases and malaria in Australia, 2008-09: annual report of the
      National Arbovirus and Malaria Advisory Committee.
AB  - The National Notifiable Diseases Surveillance System received 8,677 notifications
      of diseases transmitted by mosquitoes in Australia from 1 July 2008 to 30 June
      2009. The alphaviruses, Barmah Forest and Ross River, accounted for 6,574 (78%)
      of these notifications during 2008-09. There were 1,009 notifications of dengue
      virus infection locally-acquired in North Queensland and 484 notified cases
      resulted from overseas travel. Notification rates of dengue virus infection for
      2008-09, regardless of where infection was acquired, exceeded the five-year mean
      rate and may be attributed to increased disease activity in the Asia-Pacific
      region. North Queensland was the site of several outbreaks of locally-acquired
      dengue virus infection involving all 4 serotypes. These dengue outbreaks affected
      several locations with over 1,000 notifications. Detection of flavivirus
      seroconversions in sentinel chicken flocks across Australia provides an early
      warning of increased levels of Murray Valley encephalitis virus and Kunjin virus
      activity. Increased levels of flavivirus activity were detected in western and
      northern Australia, which prompted public health action. This action preceded 4
      notifications of Murray Valley encephalitis infections, 2 (fatal) cases acquired
      in the Northern Territory and two in Western Australia. There were no
      notifications of locally-acquired malaria in Australia and 567 notifications of
      overseas-acquired malaria during 2008-09. This annual report presents information
      of diseases transmitted by mosquitoes in Australia and notified to the National
      Notifiable Diseases Surveillance System.

PMID- 21090180
TI  - Immunisation coverage annual report, 2008.
AB  - This, the 2nd annual immunisation coverage report, documents trends during 2008
      for a range of standard measures derived from Australian Childhood Immunisation
      Register data, including overall coverage at standard age milestones and for
      individual vaccines included on the National Immunisation Program (NIP). Coverage
      by indigenous status and mapping by smaller geographic areas as well as trends in
      timeliness are also summarised according to standard templates. With respect to
      overall coverage, Immunise Australia Program targets have been reached for
      children at 12 and 24 months of age but not for children at 5 years of age.
      Coverage at 24 months of age exceeds that at 12 months of age, but as receipt of
      varicella vaccine at 18 months is excluded from calculations of 'fully immunised'
      this probably represents delayed immunisation, with some contribution from
      immunisation incentives. Similarly, the decrease in coverage estimates for
      immunisations due at 4 years of age from March 2008, is primarily due to changing
      the assessment age from 6 years to 5 years of age from December 2007. A number of
      individual vaccines on the NIP are not currently assessed for 'fully immunised'
      status or for eligibility for incentive payments. These include pneumococcal
      conjugate and meningococcal C conjugate vaccines for which coverage is comparable
      to vaccines which are assessed for 'fully immunised' status, and rotavirus and
      varicella vaccines for which coverage is lower. Coverage is also suboptimal for
      vaccines recommended for Indigenous children only (i.e. hepatitis A and
      pneumococcal polysaccharide vaccine) as previously reported for other vaccines
      for both children and adults. Delayed receipt of vaccines is an important issue
      for vaccines recommended for Indigenous children and has not improved among non
      Indigenous children despite improvements in coverage at the 24-month milestone.
      Although Indigenous children in Australia have coverage levels that are similar
      to non-indigenous children at 24 months of age, the disparity in delayed
      vaccination between Indigenous and non-indigenous children, which is up to 18%
      for the 3rd dose of DTP, remains a challenge.

PMID- 21090181
TI  - Annual report: surveillance of adverse events following immunisation in
      Australia, 2009.
AB  - This report summarises Australian passive surveillance data for adverse events
      following immunisation (AEFI) reported to the Therapeutic Goods Administration
      (TGA) for 2009, and describes reporting trends over the 10-year period 2000 to
      2009. There were 2,396 AEFI records for vaccines administered in 2009, the
      highest number reported, a 46% increase over the 1,638 in 2008. The increase was
      almost entirely due to reports related to the introduction of pandemic H1N1
      (pH1N1) 2009 influenza vaccine from September 2009 (n = 1,312) largely from the
      members of the public. The pH1N1 AEFI reporting rate for people aged > or = 18
      years was 34.2 per 100,000 administered doses compared with 2.8 for seasonal
      influenza vaccine. The rates in > or = 65 year-olds were 28.0, 1.6 and 13.3 for
      pH1N1, seasonal influenza and polysaccharide pneumococcal, respectively. The high
      reporting rate for pH1N1 vaccine is likely to be at least partly due to enhanced
      reporting seen for all new vaccines and greater levels of reporting from members
      of the public in response to the implementation of strategies to encourage
      reporting, as part of the pH1N1 program. For children < 7 years, AEFI reporting
      rates in 2009 (14.1 per 100,000 administered doses) were similar to previous
      years. There were 193 (8%) AEFI reports classified as serious; 6 deaths
      temporally associated with immunisation were reported but none were judged to
      have a causal association. As in previous years, the most commonly reported
      reactions were allergic reaction, injection site reaction, fever, headache,
      malaise, nausea and myalgia. The most commonly reported reactions following pH1N1
      influenza vaccine were allergic reaction (n = 381), headache (n = 289), fever (n
      = 235), pain (n = 186), nausea (n = 180) and injection site reaction (n = 178).
      The data within the limitation of passive surveillance provide a reference point
      for ongoing reporting of trends in AEFI by age group, severity and vaccine type
      and illustrate the value of the national TGA database as a surveillance tool for
      monitoring AEFI nationally.

PMID- 21090182
TI  - Annual report of the Australian National Poliovirus Reference Laboratory, 2009.
AB  - The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by
      the World Health Organization (WHO) for the testing of faecal specimens from
      acute flaccid paralysis (AFP) cases and operates as a regional poliovirus
      reference laboratory for the Western Pacific Region. The NPRL, in collaboration
      with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for
      cases of AFP in children in Australia, according to criteria recommended by the
      WHO. Specimens are referred from AFP cases in children and suspected cases of
      poliomyelitis in persons of any age. The WHO AFP surveillance performance
      indicator is 1 non-polio AFP case per 100,000 children less than 15 years of age.
      In 2009, the Polio Expert Committee classified 48 cases as non-polio AFP, a rate
      of 1.17 cases per 100,000 children less than 15 years of age. An additional WHO
      AFP surveillance performance indicator is that more than 80% of notified AFP
      cases have 2 faecal samples collected 24 hours apart and within 14 days of onset
      of paralysis. Adequate faecal samples were received from 16 (33.3%) of the 48
      classified cases. A poliovirus was referred via the Enterovirus Reference
      Laboratory Network of Australia from a non-AFP case and was determined to be
      Sabin-like. This case most likely represents an importation event, the source of
      which was not identified, as Australia ceased using Sabin oral polio vaccine in
      2005. The last report of a wild poliovirus importation in Australia was from
      Pakistan in 2007. In 2009, 1,604 wild poliovirus cases were reported in 23
      countries with Afghanistan, India, Nigeria and Pakistan remaining endemic for
      poliomyelitis.

PMID- 21090183
TI  - Australian Paediatric Surveillance Unit annual report, 2008 and 2009.

PMID- 21090184
TI  - Annual report of the Australian Meningococcal Surveillance Programme, 2009.
AB  - In 2009 there were 233 laboratory-confirmed cases of invasive meningococcal
      disease (IMD) analysed by the National Neisseria Network, Australia, a nationwide
      network of reference laboratories. One hundred and thirty-five isolates of
      Neisseria meningitidis from invasive cases of meningococcal disease were
      available for which the phenotypes (serogroup, serotype and serosub-type) and/or
      genotype and antibiotic susceptibility were determined. An additional 98 cases
      were confirmed by non-culture-based methods (92 by nucleic acid amplification
      testing (NAAT) and six by serology) , and where possible serotyping was
      determined. Nationally, 194 (83%) laboratory-confirmed cases where a serogroup
      was determined were infected with serogroup B and 13 (5.6%) serogroup C
      meningococci. The national total of confirmed cases has remained relatively
      stable since 2006, but the number of cases may vary between jurisdictions each
      year. New South Wales had the highest number of recorded cases in 2009. Typical
      primary and secondary disease peaks were observed in those aged 4 years or less
      and in adolescents and young adults respectively. Serogroup B cases predominated
      in all age groups and jurisdictions. The common phenotypes circulating in
      Australia continue to be B:15:P1.7 and B:4:P1.4. Although serogroup C cases were
      low, phenotype C:2a:P1.5 again predominated in this group. No evidence of
      meningococcal capsular 'switching' was detected. Approximately two-thirds of all
      isolates showed decreased susceptibility to the penicillin group of antibiotics
      (MIC 0.06 to 0.5 mg/L). All isolates remained susceptible to ceftriaxone. Four
      isolates had reduced susceptibility to ciprofloxacin, and none to rifampicin.

PMID- 21090185
TI  - Antiviral distribution data--a potential syndromic surveillance system to assist
      pandemic health service operational planning.
AB  - A pilot study was conducted in rural northern New South Wales from 15 July to 28
      August 2009, during Australia's Protect Phase response to the Influenza A H1N1
      California 7/09 pandemic. This study explored the feasibility of using
      administrative data, generated from the distribution of stockpiled antivirals, as
      a syndromic surveillance system. The purpose was to identify recently affected
      towns or those with increasing influenza-like illness activity to assist in rural
      health service operational planning. Analysis of antiviral distribution data was
      restricted to 113 general practices in rural parts of the Hunter New England Area
      Health Service. By 2 September 2009 a total of 6,670 courses of antivirals for
      adults, of which 455 courses were replacement orders, had been distributed to
      these general practices. Distribution of replacement antivirals were mapped to
      local government areas on a weekly basis. The syndromic surveillance system
      delivered timely data on antiviral distribution; used readily available software
      to generate visual activity maps in less than 30 minutes; proved adaptable; was
      of low cost; and was well received by health service planners. Full evaluation of
      the system's utility was limited by the relatively large initial distribution of
      antivirals and the brief nature of Australia's first pandemic wave. The pilot
      study demonstrated that a syndromic surveillance system based on distribution of
      supplies, such as treatment or vaccines, can support local health service
      operational planning during health emergencies.

PMID- 21090186
TI  - Evaluating the utility of emergency department syndromic surveillance for a
      regional public health service.
AB  - Communicable disease monitoring and response activities must be based upon local
      public health surveillance systems, even during infectious disease emergence,
      natural disasters, and during bioterrorism events. The NSW Department of Health
      has developed an emergency department surveillance system intended to monitor
      important public health conditions during mass gatherings and to identify
      outbreaks of importance. An evaluation of this system conducted in the Hunter New
      England region of New South Wales emphasised its usefulness when it was focused
      on a limited number of syndromes of public health importance and during mass
      gatherings and public health disaster responses.

PMID- 21090187
TI  - A new national Chlamydia Sentinel Surveillance System in Australia: evaluation of
      the first stage of implementation.
AB  - The Australian Collaboration for Chlamydia Enhanced Sentinel Surveillance
      (ACCESS) was established with funding from the Department of Health and Ageing to
      trial the monitoring of the uptake and outcome of chlamydia testing in Australia.
      ACCESS involved 6 separate networks; 5 clinical networks involving sexual health
      services, family planning clinics, general practices, antenatal clinics,
      Aboriginal community controlled health services, and 1 laboratory network. The
      program ran from May 2007 to September 2010. An evaluation of ACCESS was
      undertaken in early 2010, 2 years after the program was funded. At the time of
      the evaluation, 76 of the 91 participating sites were contributing data. The
      jurisdictional distribution of the 76 sites generally matched the jurisdictional
      distribution of the Australian population. In 2008, the chlamydia testing rates
      in persons aged 16-29 years attending the 26 general practices was 4.2% in males
      and 7.0% in females. At the 25 sexual health services, the chlamydia testing
      rates in heterosexuals aged less than 25 years in 2008 was 77% in males and 74%
      in females. Between 2004 and 2008, the chlamydia positivity rate increased
      significantly in heterosexual females aged less than 25 years attending the
      sexual health services, from 11.5% to 14.1% (P < 0.01). Data completeness was
      above 85% for all core variables except Aboriginal and/or Torres Strait Islander
      status and country of birth, which ranged from 68%-100%, and 74%-100%,
      respectively, per network. There were delays in establishment of the system due
      to recruitment of 91 sites, multiple ethics applications and establishment of
      automated extraction programs in 10 different database systems, to transform
      clinic records into a common, pre-defined surveillance format. ACCESS has
      considerable potential as a mechanism toward supporting a better understanding of
      long-term trends in chlamydia notifications and to support policy and program
      delivery.

PMID- 21090188
TI  - An outbreak of gastroenteritis due to Salmonella Typhimurium phage type 170
      associated with consumption of a dessert containing raw egg.
AB  - Eggs are frequently implicated as a source of foodborne salmonellosis. In
      February 2009 an investigation was commenced following reports of
      gastrointestinal illness among diners at a Canberra restaurant. The investigation
      sought to confirm the existence of an outbreak, identify a source and implement
      public health measures to prevent more cases. Menus and booking lists were
      obtained from the restaurant and a case-control study was commenced. A suspected
      case was defined as a person who ate at the restaurant on 13 or 14 February 2009
      and subsequently developed diarrhoea and/or vomiting. Twenty cases and 31
      controls were enrolled in the study. Eating a tiramisu dessert containing raw egg
      had a highly statistically significant association with illness (crude odds ratio
      130.50, 95% confidence interval 13.54-1605.28). Among the 20 cases, nine of 12
      stool samples were positive for Salmonella Typhimurium phage type 170 (STm 170).
      No microbiological evidence of STm 170 was obtained from the restaurant or during
      the egg trace-back investigation. This report highlights the risk associated with
      consumption of foods containing raw or undercooked shell egg.

PMID- 21090189
TI  - Potential exposure to Australian bat lyssavirus in south east Queensland: what
      has changed in 12 years?
AB  - Public health measures have been targeting potential exposure to Australian bat
      lyssavirus (ABLV) since the first recognised human cases, more than a decade ago.
      The effect of these measures on the epidemiology of notifications of potential
      exposure has not been investigated since 2003. Trends in notifications of
      potential exposure to ABLV reported to the Brisbane Southside Public Health Unit
      between November 1996 and October 2008 were examined. During the study period
      notification rates declined among all population groups and potential exposures
      were notified more promptly. The proportion of female notifications and the
      proportion of notifications from volunteer bat carers and their families and
      professional groups decreased over time. These changes over 12 years may indicate
      success of public health measures, under-reporting of potential exposure or both.
      Intentional handling of bats by untrained members of the public continues to be
      an important source of potential exposure to ABLV and requires a sustained public
      health response.

PMID- 21090190
TI  - Zoonotic tuberculosis: on the decline.
AB  - Mycobacterium bovis is a zoonotic member of the Mycobacterium tuberculosis
      complex responsible for a clinical syndrome indistinguishable from that due to M.
      tuberculosis. In Australia, infection with M. bovis has historically been
      associated with employment in the livestock industry or immigration from
      countries in which animal disease is endemic. It currently accounts for 0.2% of
      all human cases of tuberculosis within Australia. This paper describes a case of
      pulmonary M. bovis in a butcher and reviews factors responsible for the declining
      incidence of this disease in Australia.

PMID- 21090191
TI  - Penicillin-resistant Neisseria meningitidis bacteraemia, Kimberley region, March
      2010.
AB  - A 4-year-old fully immunised male presented to a regional hospital in the West
      Kimberley with fever and lethargy. Blood cultures yielded serogroup B Neisseria
      meningitidis, resistant to benzylpenicillin (minimum inhibitory concentration
      (MIC) 1.0 mg/L). The patient was treated with intravenous ceftriaxone and made a
      complete recovery. Although invasive N. meningitidis isolates with reduced
      penicillin susceptibility are not uncommon in Australia, this is the first report
      of a benzylpenicillin-resistant isolate (MIC > 0.5 mg/L) causing invasive
      disease. As benzylpenicillin is currently recommended as first line empiric and
      definitive therapy for invasive meningococcal disease, the emergence of
      penicillin-resistant N. meningitidis disease is of concern and emphasises the
      importance of ongoing surveillance for antimicrobial resistance.

PMID- 21090192
TI  - OzFoodNet quarterly report, 1 April to 30 June 2010.

PMID- 21090193
TI  - Communicable diseases surveillance.

PMID- 21090194
TI  - Healthcare reform fails to shed controversy as Congress moves closer to mid-term
      elections.

PMID- 21090195
TI  - Alreadly gone!

PMID- 21090196
TI  - Identifying revenue cycle management opportunities.
AB  - With practice bottom lines rapidly eroding, repeated threats of Medicare cuts,
      and the need to purchase expensive technology to meet the requirements of the
      American Recovery and Reinvestment Act, today's practicing physicians have no
      choice but to aggressively manage their revenue cycles. Physicians need to be
      paid in a timely fashion for each service they provide, and they need to be sure
      the payments they receive are correct.

PMID- 21090197
TI  - Identity theft and your practice.
AB  - Medical identity theft is a growing problem in America. The federal government
      has passed laws to help "prevent" identity theft. However, several powerful
      medical associations are fighting the legislation. Americans need to know what is
      happening with these laws and why these laws are important to protect providers
      from lawsuits and consumers of healthcare from medical identity theft.

PMID- 21090198
TI  - What your practice should know about Medicare RAC audits.
AB  - The Recovery Audit Contractor (RAC) Program has become permanent by statute, and
      RACs have expanded their focus and efforts to identify improper Medicare payments
      in all 50 states. Physicians and practice groups that bill Medicare Parts A and B
      may be subject to a RAC Audit. There are two types of RAC reviews and audits, and
      there are five levels of appeals available to providers when Medicare claims are
      denied or a RAC audit identifies a previous Medicare overpayment. Physicians and
      practice groups should take steps to ensure compliance with Medicare regulations
      and to be prepared prior to receiving a letter from a RAC.

PMID- 21090199
TI  - Marketing on a budget.

PMID- 21090200
TI  - Social media networking: blogging.
AB  - Social media networking is not your teenager's social media. It is a powerful
      tool that will change the way you communicate with your patients. This article
      will review the impact of social media and how social media can be a valuable
      tool for your medical practice. This is the first of a three-part article on
      social media and will discuss the use of blogging for medical practices.

PMID- 21090201
TI  - Physician M&As: what you need to know before taking the plunge.
AB  - In the current healthcare environment, many physicians are considering merging
      practices. Increasing costs, decreasing revenues, and changing regulations are
      obstacles today's physicians face, which has led many to "take the plunge" and
      merge practices. For a successful merger to occur, many factors must be
      considered. Advantages and disadvantages exist that must be weighed in order to
      determine if a merger is the best decision. This article considers the factors
      associated with merging physician practices to determine the best possible
      outcome for a physician's practice.

PMID- 21090202
TI  - Effectively using a healthcare attorney is critical to your practice's legal
      health.
AB  - Attorney jokes are legendary among physicians. However, in today's healthcare
      climate physicians can benefit by having a collaborative relationship with a
      trusted legal partner--one who understands the business and regulations of
      medicine as well as the law.

PMID- 21090203
TI  - Being part of a multi-generational medical practice team.
AB  - What happens when you find yourself working in your medical practice every day
      with co-workers who are the ages of your parents or children? Do you find
      yourself reverting to age-related roles? Do you become exasperated with or
      bewildered by the values and behaviors of older or younger colleagues? This
      article explores the challenges and opportunities the medical practice staff
      member faces when he or she is part of a multi-generational medical practice
      team. It describes the tensions that often occur when a medical practice staff
      runs the gamut from those who remember using a library card catalog and those who
      can't remember the days before Google. It describes the core values, career
      goals, key formative events, and attitudes that may have shaped the thinking and
      behavior of the four generations that may work in the medical practice today:
      Traditionalists, Baby Boomers, Generation X, and Generation Y. It suggests
      preferred communication and learning methods for staff members of different
      generations. Finally, this article offers 10 best practices for working in a
      multi-generational staff and for creating a supportive multi-generational medical
      practice culture.

PMID- 21090204
TI  - The four C's of physician relations.
AB  - With all due respect, the simple truth is that doctors don't always play well in
      the sandbox. Add in challenges such as reduced reimbursement, shifting to
      electronic records, and a merger or acquisition, and you have a recipe for
      trouble. Think marriage is difficult? Work with unhappy doctors and you'll
      appreciate the meaning of stress. The good news is that there are practical,
      proven strategies that you can use to improve colleagueship and communications,
      gain buy-in for change initiatives, reach rapid consensus, and significantly
      reduce conflict. The bad news is that there are hidden barriers to progress that
      often slow down and even completely block forward momentum. The secret is to
      determine where you can (and can't) effect change and to stay committed to your
      goals.

PMID- 21090205
TI  - Helping your patients want to pay you.
AB  - Back in the day when deductibles and copayments represented a relatively small
      share of your accounts receivable, you might have been able to get away with
      relegating patient-balance collections to your secondary list of practice
      management priorities. But in today's world of flat or declining medical revenue-
      coupled with burgeoning consumer-driven health plans--collecting those patient
      dollars has become a significant part of revenue cycle management.

PMID- 21090206
TI  - Quality/cost initiative of PPACA: an evolution in healthcare delivery?
AB  - The Patient Protection and Accountable Care Act (PPACA), signed into law by
      President Obama on March 23, 2010, contains provisions designed to materially
      change the manner in which hospitals and physicians deliver care to Medicare and
      Medicaid patients and the way they are compensated for such care. The purpose is
      to vastly improve the quality of healthcare, while at the same time lowering
      healthcare costs. This quality/cost initiative is a concept that will spell the
      future for healthcare reform. This article broadly describes the provisions of
      PPACA, along with the demonstration and pilot programs created as a result of
      PPACA, which are all designed to further the quality/cost initiative. It also
      provides some of the author's predictions as to what the future holds for
      physicians and hospitals given the government's focus on the quality/cost
      initiative.

PMID- 21090207
TI  - Going green in the medical office is more than wearing green.
AB  - Doctors will soon be facing pressures to make their practices green, i.e.,
      environmentally and ecologically friendly. Being a good doctor means caring for
      patients, and now we have to care for the planet as well. This article will
      discuss why doctors need to be conscious of the environment and offer suggestions
      for implementing eco-friendly behaviors into their medical practices.

PMID- 21090208
TI  - Recruit and hire the best fit for your practice.
AB  - Hiring for your practice is a big responsibility as well as a commitment of time
      and resources. To find and place the right person for an opening in your
      practice, consider all of the tools and methods available to you. Use the
      Internet to advertise the open position, do background and credit checks, and
      communicate with candidates clearly and securely. Coordinate your assessment of
      candidates by the effective use of employment applications, peer interviewing,
      knowledge assessment tools, and written interviews. In-person interviewing is a
      timeless skill. This article provides insights, useful tools, and practical
      advice on recruiting for a perfect fit with the position and practice.

PMID- 21090209
TI  - Inhale, exhale, e-mail: tips for effectively handling e-mail.
AB  - Today's world is all about speed and gathering information, superficial or
      otherwise. E-mail, computers and technological devices, all of which are designed
      to make us more productive and efficient, can use us up, spit us out, and leave
      us feeling inferior, ineffective, frustrated, and stressed out. Learn how to get
      control of your e-mail.

PMID- 21090210
TI  - Healthcare reform: can you get ahead of the wave?

PMID- 21090211
TI  - Over the past decade, we have been immersed in quality improvement.

PMID- 21090212
TI  - Recommendations for responding to changes in reimbursement policy.
AB  - With profound changes in reimbursement policy on the horizon, organizations are
      preparing a variety of responses to ensure long-term success. Most are
      anticipating decreases in reimbursement rates from most payers. Whether due to
      nonpayment for hospital-acquired complications and infections, reductions due to
      high readmission rates, or a move toward value-based purchasing and bundled
      payment models, the impact is predicted to be substantial. Because of these
      sweeping changes, organizations must quickly prepare a thoughtful, effective
      response to ensure their financial stability. At the heart of these global
      changes in reimbursement, including those in the healthcare reform legislation,
      is a drive toward integration, the formation of integrated delivery systems in
      response to changing financial incentives. However, the new integrated systems
      must be not just an assemblage of the required components, but a true functional
      integration in which patients experience a seamless continuum of care that is
      highly coordinated, efficient, effective, and accessible. In this article, we'll
      address changes in reimbursement and recommended responses from three
      perspectives. First, we offer a three-pronged approach for managing general
      decreases in reimbursement. Second, we highlight strategies for managing
      nonpayment for readmissions, focusing on the demonstration project in the state
      of Michigan, MI STAAR. And finally, we review managing patient care in an
      environment of bundled payment, including the interventions at the center of the
      PROMETHEUS demonstration project.

PMID- 21090213
TI  - Progression of strategies used by a healthcare system preparing for healthcare
      reform: past and present.
AB  - Strategies used by CaroMont Health to improve quality, decrease cost, and
      increase operational efficiency have ultimately aligned our system to address the
      present and future challenges confronting healthcare. Beginning with To Err is
      Human (Institute of Medicine 1999) and continuing with the healthcare reform bill
      of 2010, CaroMont Health has responded to challenges by striving to provide
      excellent patient care in a cost-effective manner. In this journey, CaroMont has
      discovered several key success factors essential in navigating this
      transformation. Our strategies reinforce the fact that improved quality and
      patient outcomes will ultimately reduce overall healthcare costs. In an ongoing
      collaboration with the Premier healthcare alliance, CaroMont Health has evolved
      from focusing on process metrics to delivering value-based care. CaroMont is now
      positioned to enter the new world of value-based delivery leading to
      accountability for community health.

PMID- 21090214
TI  - Provider alignment is integral to future success.

PMID- 21090215
TI  - Payment changes: a catalyst for quality.

PMID- 21090216
TI  - New reimbursement models challenge providers and create opportunities.

PMID- 21090218
TI  - Tech savvy. Silicon Valley hospital embraces its environment.

PMID- 21090217
TI  - Patient-centered care.

PMID- 21090219
TI  - Just right. Designing for hospital efficiency and flexibility.

PMID- 21090220
TI  - Hygienic design. Enhancing infection prevention in the patient environment.

PMID- 21090221
TI  - Healthy interface. Designing for people and technology.

PMID- 21090222
TI  - Locked up. Trends in hospital access control devices and technologies.

PMID- 21090223
TI  - Looking forward. FGI guidelines strive to advance imaging design.

PMID- 21090224
TI  - Lean transformations. Planning a 'lean' health care makeover.

PMID- 21090225
TI  - Body talk. How the endocrine system controls blood glucose.

PMID- 21090226
TI  - Sweating to the beat. Your heart rate and your workout.

PMID- 21090227
TI  - Remaking Thanksgiving.

PMID- 21090228
TI  - Cooking with your kids.

PMID- 21090229
TI  - A family affair. Get your loved ones to eat healthfully without causing a feud.

PMID- 21090230
TI  - Paging Dr. Right. How to find a great doc--and get the most out of your visit.

PMID- 21090231
TI  - Safer at school. New laws in two states protect students with diabetes.

PMID- 21090232
TI  - Power to the patient. Helping people with diabetes assess their own progress.

PMID- 21090233
TI  - [Mitochondrial genome and human mitochondrial diseases].
AB  - Today there are described more than 400 point mutations and more than hundred of
      structural rearrangements of mitochondrial DNA associated with characteristic
      neuromuscular and other mitochondrial syndromes, from lethal in the neonatal
      period of life to the disease with late onset. The defects of oxidative
      phosphorylation are the main reasons of mitochondrial disease development.
      Phenotypic diversity and phenomenon of heteroplasmy are the hallmark of
      mitochondrial human diseases. It is necessary to assess the amount of mutant
      mtDNA accurately, since the level of heteroplasmy largely determines the
      phenotypic manifestation. In spite of better understanding of the processes of
      phenotypic expression, currently there are no adequate treatments for
      mitochondrial diseases.

PMID- 21090234
TI  - [Core promoters as an example of the evolution of views on molecular mechanisms
      of vital activity under the impact of whole-genome information].
AB  - DNA sequences of a large number of animal genomes, combined with the information
      on new classes of regulatory elements traditionally viewed as intergenic, led to
      the revision of the concept of the genome as a linear sequence of genes with
      their promoters spaced by distinct intergenic regions. Instead, there emerged a
      conception of 'transcriptional landscape' characterized by the practical absence
      of boundaries between what was commonly considered genes. The concept of the core
      promoter, the main transcriptional cis-acting element, was also dramatically
      changed. The knowledge of the mechanisms of functioning of this central element
      of the cellular transcription system underlies the understanding of metazoan
      transcription in general. The review attempts to summarize the data on core
      promoters obtained in the last 7-10 years and to trace the evolution of the
      conception of them. This evolution led finally to the understanding that core
      promoters are active participants of the transcription regulation process rather
      than just passive scaffold for assembling preinitiation transcription complexes.

PMID- 21090235
TI  - [Molecular genetic evidences of a deep phylogenetic discontinuity between Asian
      and European races of pygmy wood mouse based on the data of mtDNA cytochrome b
      gene variability].
AB  - The variability of mitochondrial DNA (mtDNA) cytochrome b gene sequences of pygmy
      wood mouse Sylvaemus uralensis (Pallas, 1811) from local populations of European
      regions of Russia, West Siberia, and neighboring countries (Moldova, Kazakhstan,
      Uzbekistan, and Turkmenistan) have been studied. Phylogenetic analysis both our
      results and data from GenBank revealed two clusters of haplotypes: "western" with
      reliable subdivision into two sequence groups and "eastern" without valid
      differentiation. Clusters correspond exactly to European and Asian races of pygmy
      wood mouse recognized earlier on the basis of biochemical and karyological
      variability. We suppose that Asian race can be considered as independent
      allopatric species. This is supported by following evidences: high divergence
      level (which proposes more than 1 mya of divergent evolution) between races,
      absence of common haplotypes and hiatus between main peaks of mismatch
      distribution, differences in frequencies of codon usage, fixed nucleotide
      substitutions in cyt b gene, and also changes in amino acid sequences of
      cytochrome b. Only specimens of the western phylogenetic linage can be considered
      as S. uralensis (Pallas, 1811) while according to the first description S. tokmak
      (Severtzov, 1873) may be considered as species united specimens of eastern
      phylogenetic linage.

PMID- 21090236
TI  - [Genetic diversity of X-chromosome in populations of aboriginal Siberian ethnic
      groups: linkage disequilibrium structure and haplotype philogeography of ZFX
      locus].
AB  - The structure of gene pool of the Siberian aboriginal population has been
      described based on the data on polymorphism of ZFX gene located on X-chromosome.
      In ten populations under study 49 haplotypes have been determined, three of which
      are presented with high frequency. Comparing the obtained results with the
      available data from HapMap project unique "African" haplotypes were revealed,
      which occurred in Yoruba population with the frequency of 3-7% and were not found
      in other populations. A coefficient of genetic differentiation of the Siberian
      ethnic groups under study amounted to 0.0486. Correlation analysis involving
      Mantel test did not reveal any significant correlations between a matrix of
      genetic distances and the matrices of geographic, linguistic and anthropological
      differences, where a maximum coefficient was obtained at the comparison with the
      anthropological matrix. Phylogenetic analysis proved strong isolation of African
      population from the other investigated ethnic groups. The Siberian populations
      were subdivided into two separate clusters: the first one included Yakuts,
      Buryats and Kets, while the second cluster included Altaians, Tuvinians and
      Khanty. A principal component analysis enabled to combine the investigated
      populations in three groups, which clearly differed by a degree of manifestation
      of Caucasoid and Mongoloid components. The first group included Europe
      inhabitants and one of Khanty populations, the second one--populations of South
      Siberia and China inhabitants. Mongoloid populations of East Siberia, the
      Japanese and Kets were combined in the third group. The results of barrier
      analysis revealed similar structure of genetic differentiation in the Siberian
      population. Linkage disequilibrium structure was obtained for six ethnic groups
      of Siberia. A unified linkage block by ten SNP of ZFX gene was found in five of
      the presented ethnic groups (excluding Ket population).

PMID- 21090237
TI  - [Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR,
      C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer
      in West Siberian Region of Russia].
AB  - Breast cancer is the most incident cancer among women. We investigated the role
      of polymorphisms of folate metabolizing genes MTHFR (C677T and A1298C), SHMT1
      (C1420T) and MTHFD (G1258A) in genetic susceptibility to this type of cancer. We
      determined allele and genotype frequencies in case (850 women with sporadic form
      of breast cancer) and control (810 women) groups. None of these polymorphisms was
      significantly associated with breast cancer risk. To increase statistical power
      of our study, we conducted a meta-analysis which included published genotype data
      and the results of our work. Meta-analysis also revealed no significant
      association of studied SNPs with breast cancer.

PMID- 21090238
TI  - [Analysis of linkage and association of alleles of proinflammatory cytokines
      genes IL-6, IFNg and TNF with multiple sclerosis using transmission
      disequilibrium test (TDT)].
AB  - Proinflammatory cytokines Interleukin-6 (IL-6), Interferon-gamma (IFNg) and Tumor
      necrosis factor (TNF) are known as participants of inflammation and play an
      important role in pathogenesis of multiple sclerosis (MS). Based on literature
      data about influence of SNPs G(-308)A of TNF gene, A(+874)T of IFNG gene and G(
      174)C of IL-6 gene on production of these cytokines, we investigated association
      of these polymorphic sites with MS. Linkage and association of alleles of these
      genes with MS was analyzed by transmission disequilibrium test (TDT). In
      investigated group of 104 nuclear families of Russian ethnicity it was found that
      TNF* (-308)A allele transmitted from healthy heterozygous parents to affected
      children more frequently (p = 0.01). Linkage/association of IFNG and IL-6 alleles
      with MS was not revealed. Thus, data obtained indicate the participation of TNF
      gene in MS susceptibility in Russians.

PMID- 21090239
TI  - [Stress response genes expression analysis of barley Hordeum vulgare under space
      flight environment].
AB  - Transcriptome of barley Hordeum vulgare grown aboard International Space Station
      (ISS) was analyzed by means of microarray. It was revealed 500 genes with mRNA
      level, changed more than two folds in space environment. Among them are genes
      encoding stress response proteins, videlicet Heat Shock Proteins (HSP),
      Pathogenesis-Related Proteins (PR) and Antioxidant Proteins. Further analysis of
      these genes by real time PCR showed enhanced transcription level of Reactive
      oxygen Species (ROS) scavenging genes. The mRNA level of superoxide dismutase
      (sod) was 6 folds higher in space environment when compare to Earth conditions.
      Glutamyl transferase gene expression was enhanced 24 times in space.
      Transcription of catalase gene (cat) was increased 18 times and of ascorbate
      peroxidase was increased 3 times in space in comparison with ground control. For
      the first time it was shown that space flight environment may induce oxidative
      stress in plants.

PMID- 21090240
TI  - [Gene IL6 G(-174)C and gene IL10 G(-1082)A polymorphisms are associated with
      unfavourable outcomes in patients with acute coronary syndrome].
AB  - We investigated the association of gene IL6 G(-174)C polymorphism and gene IL10
      G(-1082)A polymorphism with coronary artery disease (CAD) in the Russian
      population. A total of 1145 patients with CAD diagnose on the basis of clinical
      studies in cardiological hospitals of Moscow, St -Petersburg, Kazan, Chelyabinsk,
      Perm, Stavropol and Rostov-on-Don. Supervision term was 9.10 +/- 5.03 months (the
      maximum term 18 months). In case of gene IL10 G(-1082)A polymorphism we
      determined that patients with CAD diagnose and A alleles gene IL10 had
      unfavorable outcome more often than patients with homozygous G alleles. Survival
      time from end point from carrier genotype GA and AA is 11.68 +/- 0.67 months
      against 12.69 +/- 0.65 months from carrier phenotype GG gene IL10 (chi2 = 4.13, p
      = 0.042). The group studied do not differ significantly with respect to the
      distributions of gene IL6 G(-174)C alleles and genotypes. However in case
      combined group studies of gene IL10 G(-1082)A polymorphism and IL6 G(-174)C
      polymorphism we determined that patients with CAD diagnose and carrier genotype
      GG gene IL6 and genotype GA and AA gene IL10 had unfavorable outcome more often
      (survival time 11.01 +/- 1.24 months) than patients with genotype CC and CG gene
      IL6 and genotype GG gene IL10 (survival time 13.28 +/- 0.83 months) chi2 = 10.23,
      p = 0.017. The obtained data allows assuming the important role of the IL6 and
      IL10 genes which are responsible for functioning of inflammation system, in the
      accelerated formation of failures at the patients who had a coronary syndrome.

PMID- 21090241
TI  - [Novel conservative domain of SAYP coactivator mediates TFIID and Brahma
      transcriptional complexes interaction].
AB  - In the S2 cell system of Drosophila melanogaster a key protein domain mediating
      the interaction of TFIID and Brahma transcriptional complexes into the BTFly
      supercomplex has been shown to be an evolutionary conserved SAY domain of the
      SAYP. TFIID and Brahma coactivators participated in the reporter gene activation
      induced by the SAY domain in cellular nuclei. The TFIID and Brahma components
      directly interacting with the SAY domain were identified.

PMID- 21090242
TI  - [Downregulation of activated leukemic oncogenes AML1-ETO and RUNX1(K83N)
      expression with RNA-interference].
AB  - In the present study we have applied the siRNA approach for substantial reduction
      of AML1-ETO and RUNX1 (K83N) expression, which are frequently found in the
      leukemic cells. We have designed small hairpin RNAs (shRNA) for targeting AML1
      ETO oncogene and a region close to the 5'-untranslated region of mRNA for the
      mutant RUNX1 (K83N) oncogene and expressed the shRNAs in lentiviral vectors. We
      report a stable reduction in expression of the oncogenes following the
      introduction of shRNAs into cells.

PMID- 21090243
TI  - [Cold shock domain proteins in the extremophyte Thellungiella salsuginea (salt
      cress): gene structure and differential response to cold].
AB  - Four genes encoding cold shock domain (CSD) proteins have been identified in salt
      cress [Thellungiella salsuginea (halophila), an extremophyte currently recognized
      as a promising model for studying stress tolerance]. The deduced proteins prove
      highly homologous to those of Arabidopsis thaliana (up to 95% identity) and are
      accordingly enumerated TsCSDP1-TsCSDP4; after the N-proximal conserved CSD, they
      have respectively 6, 2, 7, and 2 zinc finger motifs evenly spaced by Gly-rich
      stretches. Much lower similarity (approximately 45%) is observed in the regions
      upstream of TATA-box promoters of TsCSDP1 vs. AtCSP1, with numerous distinctions
      in the sets of identifiable cis-regulatory elements. Plasmid expression of sCSDP1
      rescues a cold-sensitive cup-lacking mutant of Escherichia coli, confirming that
      the protein is functional. In leaves of salt cress plants under normal
      conditions, the mRNA levels for the four TsCSDPs relate as 10: 27: 1: 31.
      Chilling to 4 degrees C markedly alters the gene expression; the 4-day dynamics
      are different for all four genes and quite dissimilar from those reported for
      their Arabidopsis homologues under comparable conditions. Thus, the much greater
      cold hardiness of Thellungiella vs. Arabidopsis cannot be explained by structural
      distinctions of its CSDPs, but rather may be due to expedient regulation of their
      expression at low temperature.

PMID- 21090244
TI  - [On the role of selective silencer Freud-1 in the regulation of the brain 5
      HT(1A) receptor gene expression].
AB  - Selective 5-HT(1A) receptor silencer (Freud-1) is known to be one of the main
      factors for transcriptional regulation of brain serotonin 5-HT(1A) receptor.
      However, there is a lack of data on implication of Freud-1 in the mechanisms
      underlying genetically determined and experimentally altered 5-HT(1A) receptor
      system state in vivo. In the present study we have found a difference in the 5
      HT(1A) gene expression in the midbrain of AKR and CBA inbred mouse strains. At
      the same time no distinction in Freud-1 expression was observed. We have revealed
      90.3% of homology between mouse and rat 5-HT(1A) receptor DRE-element, whereas
      there was no difference in DRE-element sequence between AKR and CBA mice. This
      indicates the absence of differences in Freud-1 binding site in these mouse
      strains. In the model of 5-HT(1A) receptor desensitization produced by chronic 5
      HT(1A) receptor agonist administration, a significant reduction of 5-HT(1A)
      receptor gene expression together with considerable increase of Freud-1
      expression were found. These data allow us to conclude that the selective
      silencer of 5-HT(1A) receptor, Freud-1, is involved in the compensatory
      mechanisms that modulate the functional state of brain serotonin system, although
      it is not the only factor for 5-HT(1A) receptor transcriptional regulation.

PMID- 21090245
TI  - [The role of the glycoprotein gp130 in serotonin mediator system in mouse brain].
AB  - Glycoprotein gp130 is involved in signaling out of significant cytokine receptors
      as interleukin-6 (IL-6), leukemia inhibitory factor and ciliary neurotrophic
      factor, which play critical role in immunity, inflammation and neurogenesis. IL-6
      and brain neurotransmitter serotonin are involved in the mechanism of depression.
      The aim of this work was to investigat the role of protein gp130 in the
      regulation of expression of genes, coding the key enzyme of serotonin synthesis-
      tryptophan hydroxylase 2 (TPH2), 5-HT-transporter, 5-HT(1A)- and 5-HT(2A)
      receptors of serotonin. The study was carried out on adult mouse males of AKR and
      congenic AKR.CBA-D13Mit76 strains, created by transfer of the fragment of
      chromosome 13 containing the gene coding gp130 protein from CBA/Lac strain to the
      genome of AKR/J strain. Decreased expression of 5-HT(1A) - 5-HT(2A)-receptor
      genes in hippocampus midbrain and TPH2 gene in midbrain in AKR.CBA-D13Mit76 mice
      compared with AKR mice were shown. Activation of nonspecific immunity by
      bacterial endotoxin lipopolysaccharide (LPS) administration did not affect the
      genes expression in AKR mice, but increased 5-HT(2A)-receptor expression in
      midbrain and decreased 5-HT(1A)-receptor expression in cortex in AKR.CBA-D13Mit76
      mice. The results indicate: 1) the participation of gp130 in the regulation of
      TPH2, 5-HT(1A)- and 5-HT(2A)-receptor genes and 2) association of this protein in
      the genetically determined sensitivity to LPS.

PMID- 21090246
TI  - [Secondary structure of SsoII-like (cytosine-5)-DNA methyltransferases N-terminal
      region determined by circular dichroism spectroscopy].
AB  - (Cytosine-5)-DNA methyltransferase SsoII (M.SsoII) has a long N-terminal region
      (1-71 residues) preceding the sequence with conservative motifs, which are
      characteristic for all DNA methyltransferases of such kind. The presence of this
      region provides M.SsoII capability to act as a transcription regulator in SsoII
      restriction-modification system. To perform its regulatory function, M.SsoII
      binds specifically to a 15-mer inverted repeat in the promoter region of SsoII
      restriction-modification system genes. In the present work, properties of the
      protein delta(72-379)M.Ecl18kI are studied, which is a deletion mutant of the
      SsoII-like DNA-methyltransferase M.Ecl18kI and is homologous to M.SsoII N
      terminal region. delta(72-379)M.Ecl18kI capability to bind specifically a DNA
      duplex containing the regulatory site is demonstrated. However, such a binding
      takes place only in the presence of high protein excess relative to DNA, which
      could indicate an altered structure in the deletion mutant in comparison with the
      full-length M.SsoII. Circular dichroism spectroscopy demonstrated that delta(72
      379)M.Ecl18kI has a strongly pronounced secondary structure and contains 32% a
      helices and 20% beta-sheets. Amino acid sequences alignment of M.SsoII N-terminal
      region and transcription factors of known spatial structure is made. An
      assumption is made how alpha-helices and beta-sheets are arranged in M.SsoII N
      terminal region.

PMID- 21090247
TI  - [X-ray diffraction and biochemical studies of W34F mutant ribonuclease binase].
AB  - The structures of two crystal modifications of the W34F mutant ribonuclease from
      the bacterium Bacillus intermedius (binase) were solved and refined at 1.7 and
      1.1 A resolution. The kinetic parameters of the hydrolysis of substrates of
      different lengths (GpU, GpUp, and poly(I)) by binase and its W34F mutant were
      investigated and compared. The catalytic activity of the enzymes was shown to
      increase with increasing length of the substrate. The substitution of tryptophan
      for phenylalanine does not lead to a change in the activity of the enzyme but
      results in a decrease in the binding constants for substrates containing more
      than one phosphate groups. A comparison of the structure of the mutant enzyme
      with the previously established structures of binase and its complexes with
      sulfate ions and guanosine monophosphate showed that the difference in their
      kinetic parameters is related to the fact that the mutant ribonuclease cannot
      bind the second phosphate group. Both crystal modifications of the mutant binase
      contain dimers, like in the crystal structure of binase studied previously. In
      these dimers, only one enzyme molecule can bind the substrate molecule. Since the
      dimers were found in the crystals grown under four different conditions, it can
      be suggested that the enzyme can exist as dimers in solution as well. Mutants of
      binase, which could exclude the formation of dimers, are suggested.

PMID- 21090248
TI  - [5,10,15,20-Tetra-(N-methyl-3-pyridyl)porphyrin destabilizes the anti-parallel
      telomeric quadruplex d(TTAGGG)4].
AB  - We studied the parameters of binding of 5,10,15,20-tetra-(N-methyl-3
      pyridyl)porphyrin (TMPyP3) to the anti-parallel human telomeric G-quadruplex
      d(TTAGGG)4, the oligonucleotide dTTAGGGTTAGAG(TTAGGG)2 that does not form a
      quadruplex structure, as well as to the double stranded d(AC)8 x d(GT) and single
      stranded d(AC)8 and d(GT)8 DNAs. The analysis of absorption revealed that the
      binding constants and the number of DNA binding sites for TMPyP3 were d(AC)8 <
      d(GT)8 < d(AC)8 x d(GT)8 = d(TTAGGG)4 < dTTAGGGTTAGAG(TTAGGG)2. We demonstrated
      for the first time that the binding constant of TMPyP3 with the non-quadruplex
      chain dTTAGGGTTAGAG(TTAGGG)2 (1.3 x 10(7) M(-1)) is approximately 3 times bigger
      than the binding constant with the quadruplex d(TTAGGG)4 (4.6 x 10(6) M(-1)).
      Binding of two TMPyP3 molecules to d(TTAGGG)4 led to a decrease of
      thermostability of the G-quadruplex (deltaT(m) = -8 degrees C). Circular
      dichroism spectra of TMPyP3:d(TTAGGG)4 complexes revealed a shift of DNA
      structure from the G-quadruplex to an irregular chain. We hypothesize that
      partial destabilization of the telomeric G-quadruplex by TMPyP3 might be a reason
      for relatively low potency of this ligand as a telomerase inhibitor, as well as
      its marginal cytotoxicity for cultured tumor cells.

PMID- 21090249
TI  - [Thermodynamics of zinc binding to human S100A2].
AB  - The regulatory protein S100A2 is localized in the cell nucleus and takes part in
      the regulation of the cell cycle and cancerogenesis. It belongs to a large family
      of S100 proteins and can simultaneously bind calcium and zinc ions. Using a
      direct thermodynamical method of isothermal titration calorimetry we have
      determined that in the absence of calcium ions the S100A2 protein can bind three
      zinc ions per each monomer. Besides that it was determined that the
      thermodynamics of zinc binding to different binding sites on the S100A2 are
      significantly different. Zinc binding to the first two sites on the S100A2 is
      enthalpically unfavorable and is driven only by entropic factors, while the
      binding of the third zinc ion is enthalpically favorable. Analysis of the zinc
      ion adsorption isotherms shows that their binding occurs in a consecutive order.

PMID- 21090250
TI  - [Advance in study on active protein and peptide produced by marine bacteria--a
      review].
AB  - Biological active resources are various and abundant in the ocean. With this
      realization, active proteins and peptides especially marine bacteria active
      proteins and peptides have attracted much attention recently. The achievements in
      the study of bioactivities of marine bacterial proteins and peptides were
      reviewed in this paper. Acquisition and potential applications of these marine
      bacteria active products were then proposed. Additionally, we focused on the
      prospective outline on the study of this field.

PMID- 21090251
TI  - [Advances in the study of nisin resistance--a review].
AB  - Nisin, a lantibiotic produced by some species of Lactococcus lactis, has broad
      antibacterial spectrum against Gram-positive bacteria species, especially those
      with close phylogenetic relationship to the nisin producing strain. The broad use
      of nisin did not lead to widespread resistance. However, some non-nisin producing
      bacteria could develop certain mechanisms of resistance against nisin when
      growing under laboratory or nature selection pressure. Nisin resistance mainly
      involved two strategies, namely, the non-specific physiological isolation
      mechanism (by the change of cell wall or membrane structure and composition) and
      the specific protease-mediated mechanism. This review introduced the advances in
      the study of nisin resistance mechanism.

PMID- 21090252
TI  - [Identification and metabolism characterization of a Clostridium lituseburense
      strain isolated from high-altitude soil].
AB  - OBJECTIVE: We studied the physiological, biochemical properties and metabolism of
      Clostridium lituseburense P4-1 from soil in Namucuo. METHODS: We adopted Hungate
      anaerobic technique to get Strain P4-1 from soil in Namucuo. Through
      physiological, biochemical and phylogenetic analysis, we identified the strain P4
      1. RESULTS: Cells were Gram-positive and spore-forming. It grew between 13 and 40
      degrees C (optimum at 37 degrees C), between pH value 5.0 and 10.O (optimum at
      7.5-8.0), and with the presence of NaCl between 0%-5%. Strain P4-1 could
      metabolize many carbon sources including glucose, melibiose and mannitol.
      Metabolites of glucose were acetate, butyrate, propionate, CO2, and little H2.
      Based on 16S rDNA studies, strain P4-1 was most close to Clostridium
      lituseburense DSM 797 (M59107) with 98.7% similarity. Strain P4-1 could degrade p
      toluene sulfonate. CONCLUSION: Strain P4-1 tolerated low temperature, salt and
      could degrade p-toluene sulfonate. Its metabolites produced by fermentation of
      glucose could improve the soil micro-environment. It was significant for strain
      P4-1 to be utilized in the wastewater treatment.

PMID- 21090253
TI  - [Identification and biodiversity of yeasts from Qula in Tibet and milk cake in
      Yunnan of China].
AB  - OBJECTIVE: To analyze the biodiversity and distribution of the yeast species of
      Qula in Tibet and milk cake in Yunnan, and to provide essential data for the
      utilization of yeasts in the traditional dairy products of China. METHODS: Forty
      one yeast strains were isolated from 5 samples of Qula in Tibet and 8 samples of
      milk cake in Yunnan. The isolates were identified by the large-subunit (26S) rDNA
      gene D1/D2 domain sequences analysis. RESULTS: The population of yeast in Qula
      varied from 10(6) cfu/g to 10(7) cfu/g. The content of yeast ranged from 102
      cfu/g to 10(6) cfu/g in milk cake. The average population of yeast in Qula was
      higher than milk cake for 34 folds. These strains were grouped in 12 species
      belonging to 10 genera. The dominant species in Qula were Pichia fermentans and
      Saccharomyces cerevisiae, but Candida zeylanoides and Pichia cactophila were
      major population in milk cake. The results showed that Pichia was the dominant
      genera both in Qula and milk cake. CONCLUSION: There existed that yeasts of great
      biodiversity both of Qula in Tibet and milk cake in Yunnan, but quite different
      from each other.

PMID- 21090254
TI  - [Characterizations of avian influenza virus H6N6 subtype isolated from domestic
      Muscovy duck].
AB  - OBJECTIVE: To enrich the epidemiologic data of the waterfowl origin avian
      influenza virus (AIV). METHODS: The full genome of A/Muscovy
      Duck/Fujian/FZ01/2008 (H6N6), which was first isolated from domestic Muscovy duck
      in Fujian Province in southern China at 2008, was cloned and sequenced by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: The motif of
      hemagglutinin (HA) cleavage site was PSMKVIV GL, which is a molecular
      characteristic of low pathogenic AIV, and the intravenoys pathogenicity index
      (IVPI) was 0.15. The HA gene, NP gene, gene and PB2 gene nucleotide sequences had
      similarity highest with A/duck/Kingmen/E322/04 (H6N2) at 94.2%, 95.7%, 97.2% and
      95.6%, shared the same phylogenetic lineage. The neuraminidase (NA) gene had
      similarity highest with A/duck/Eastern China/01/2007 (H4N6) at 97.1 per cent, and
      also had 11 continuous amino acids (TNSTTTIINNN) deletion in the NA gene stalk
      region, which was first reported had deletion 11 amino acids in N6 subtype AIV NA
      genes' ORF. The NA gene had familiar phylogenetic relationship with H4N6 subtype
      AIV. The NS gene, PB1 gene and the PA gene had genetically close relationships
      with the H5N1 high pathogenic AIV strains isolated in Hong Kong at 1997. The
      eight genes also showed any immediate ancestor with other H6N6 subtype avian
      influenza viruses isolated in North America. CONCLUSION: These data showed that
      A/Muscovy Duck/Fujian/FZ01/2008 (H6N6) was possibly a reassortant virus derived
      from H6N2 subtype, H4N6 subtype and H5N1 subtype AIV.

PMID- 21090255
TI  - [HrpD6 gene determines Xanthomonas oryzae pv. oryzae to trigger hypersensitive
      response in tobacco and pathogenicity in rice].
AB  - OBJECTIVE: Xanthomonas oryzae pv. oryzae (Xoo) possesses a type III secretion
      system (T3 S), encoded by a hpa-hrp-hrc cluster, including hrpD6, to inject T3S
      effectors into plant cells to trigger hypersensitive response (HR) in nonhost
      tobacco and pathogenicity in susceptible host rice. However, it is unclear what
      roles of Xoo hrpD6 gene plays in HR in tobacco and in pathogenicity in rice.
      METHODS: In this study, we constructed a deletion mutant of hrpD6 gene by using
      marker-exchange method. PCR and Southern blot analysis demonstrated that the
      hrpD6 gene was knocked out successfully. RESULTS: in planta assays indicated the
      hrpD6 mutant, delta PhrpD6, lost the ability to induce HR in tobacco, to trigger
      water-soaked symptoms in seedlings rice and to cause bacterial blight in adult
      rice. Importantly, the bacterial growth in rice tissues was tremendously reduced.
      Complementation assays confirmed that hrpD6 gene could restore HR induction in
      tobacco, pathogenicity and bacterial growth in rice to the mutant delta PhrpD6.
      Reverse transcriptional polymerase chain reaction (RT-PCR) revealed that the
      expression of hrpD6 was not only induced by rice cells, but also controlled by
      hrpG and hrpX. Intriguyingly, the expression of hpal, encoding a harpin protein,
      was found to be dependent on hrpD6, implying that hrpD6 regulates the expression
      of hpal. Immunobloting assay confirmed that the mutation of hrpD6 affect the
      secretion of Hpal through T3S. CONCLUSION: The mutant lost the ability of
      triggering hypersensitive response in nonhost tobacco and pathogenicity in host
      rice is due to that hrpD6 regulates the expression of hpal gene and the mutation
      in hrpD6 affects the secretion of T3S effectors, like Hpa1, through T3SS. Our
      results provide molecular clues to understand whether hrpD6 is involved in the
      formation of T3S apparatus and in regulation of other hpa-hrp-hrc gene expression
      or not for HR induction in tobacco and pathogenicity in rice.

PMID- 21090256
TI  - [Identification and characteristics of a marine aerobic denitrifying bacterium].
AB  - OBJECTIVE: An aerobic denitrifying bacterium, strain 2-8, was isolated from a
      biological aerated filter in a recirculating marine aquaculture system, phylogeny
      and characteristics of the strain was further studied. METHODS: Sequence of the
      16S rRNA gene was analyzed and the factors affect the denitrifying ability of
      strain 2-8 were investigated, including carbon source, C/N ratio, initial pH,
      NaCl concentration, temperature and shaker speed. RESULTS: Strain 2-8 was
      identified as Pseudomonas sp. based on the analysis of its 16S rRNA gene sequence
      which showed highest similarity (99.9%) to Pseudomonas segetis FR1439(T)
      (AY770691). The results indicated that carbon source and C/N ratio exhibited
      significant influences on aerobic denitrifying capacity of strain 2-8. Strain 2-8
      could grow a little on acetate, succinate and citrate as sole carbon source, and
      the removal rates of NO3- -N at 140 mg/L were higher than 65% despite of the
      accumulation of NO2- -N around 35 mg/L. It grew quite well on glucose as sole
      carbon source, however, the removal rate of nitrate was not so high as on other
      carbon source. The optimum C/N ratio was 15, as lower C/N ratios may lead to
      nitrite accumulation. The optimum temperature and pH for its aerobic
      denitrification were 30 degrees C and 7.5, respectively. Strain 2-8 could grow
      and exhibit aerobic denitrifying ability at a wide range of NaCl concentrations
      (0-30 g/L). The highest nitrogen removal appeared under the condition of 160
      r/min shaking culture. CONCLUSION: When cultured in the conditions of NO3- -N at
      140 mg/L, sodium citrate as sole carbon source, C/N ratio at 15, pH 7.5, NaCl at
      30 g/L, 30 degrees C and 160 r/min of the shaker, strain 2-8 removed up to 92% of
      the nitrogen within 48 hours, and no nitrite accumulation.

PMID- 21090257
TI  - [Effect of acetyl-CoA synthase gene overexpression on physiological function of
      Saccharomyces cerevisiae].
AB  - OBJECTIVE: The aim of our work is to investigate the effects of overexpression of
      two acetyl-CoA synthase genes, ACS1 and ACS2, on the physiological functions of
      Saccharomyces cerevisiae. METHODS: We overexpressed ACS1 and ACS2 in S.
      cerevisiae CEN. PK2 with shuttle vector pY26-TEF-GPD. We determined and compared
      the physiological parameters of the parent strain to the ACS1/2 overexpressed
      strains, including the intracellular acetyl-CoA content, ATP content, mevalonate
      pathway, and the tolerance to ethanol stress. RESULTS: Compared to the parent
      strain, the overexpression of ACS1 and ACS2 led to: (1) The intracellular acetyl
      CoA content increased by 2. 19-fold (ACS1) and 5.02-fold (ACS2), respectively;
      (2) The intracellular ATP content increased by 3.92-fold (ACS1) and 2.05-fold
      (ACS2), respectively; (3) The transcription levels of the seven key genes in
      mevalonate pathway were upregulated, therefore, more carbon flux was channeled
      into the mevalonate pathway, which could provide precursor for terpenes
      synthesis; (4) The tolerance to high content of ethanol was enhanced, especially
      for the ACS1 overexpression strain. CONCLUSION: The results presented here
      demonstrated that the overexpression of acetyl-CoA synthase can enhance the
      carbon flux into mevalonate pathway and improve the tolerance of S. cerevisiae to
      high content of ethanol, which is the main byproduct of the fermentation process
      with the yeast.

PMID- 21090258
TI  - [Antibacterial activity and mechanism of luteolin on Staphylococcus aureus].
AB  - OBJECTIVE: To investigate the antibacterial activity and mechanism of luteolin on
      Staphylococcus aureus. METHODS: The antibacterial activity and mechanism
      experiments were carried out by using 2, 3, 5-triphenyl tetrazolium chloride
      (TTC), determining membrane penetrability, the change of SDS-PAGE protein spectra
      and 4 6-diamidino-2-phenylindole (DAPI) staining assay. RESULTS: Luteolin could
      affect the membrane permeability of Staphylococcus aureus, but not destroy the
      membrane integrity directly. After treated with luteolin for 16 hours, the total
      content of proteins decreased to 64.54%, the quantity of both DNA and RNA reduced
      to 48.44% and 39.35% respectively. The activity of DNA topoisomerase I and II was
      inhibited completely by 1.6 mg/mL luteolin. CONCLUSION: Luteolin showed obvious
      antibacterial activity against Staphylococcus aureus. The antibacterial mechanism
      of luteolin is that it could inhibit the activity of DNA topoisomerase I and II,
      which resulted in some decrease in the nucleic acid and protein synthesis.

PMID- 21090259
TI  - [Burkholderia cepacia lipase gene modification and its constitutive and inducible
      expression in Pichia pastoris].
AB  - OBJECTIVE: To achieve fast, safe and stable expression of Burkholderia cepacia
      lipase in Pichia pastoris. METHODS: We first amplified B. cepacia lipase gene,
      and then analyzed the codon usage of B. cepacia and Pichia, lipase gene signal
      peptide with bioinformatics methods. On this basis, we applied the overlap PCR to
      modify the lipase gene and finally got the optimized gene with Pichia codon usage
      and lower G + C content. Subsequently, we cloned the optimized and wild lipase
      gene into vector pGAPZalpha and pPIC9K, respectively. As a result, constitutive
      expression vector pGAPlipW, pGAPlipO and inducible expression vector pPIClipW,
      pPIClipO were obtained. Finally, we electroporated these expression vectors into
      GS115, and therefore, got a series of engineering strains. After fermentation and
      NTA resin purification, the enzymatic properties of lipase were studied. RESULTS:
      The lipase activities of pPIClipW, pPIClipO, pGAPlipW and pGAPlipO were 37.8
      U/mL, 129.5 U/mL, 40.2 U/mL, and 184.3 U/mL, respectively. The optimized lipase
      activity increased 4.6-fold. Enzymatic properties study showed that the optimal
      temperature and pH was 60 degrees C and 9.0, respectively. The lipase was rather
      stable at 40 degrees C - 65 degrees C and pH 6.0-pH10.0. CONCLUSION: After
      overlap PCR modification, the lipase expression efficiency in Pichia was
      significantly increased, which indicates that the overlap PCR modification is a
      potential strategy for lipase overexpression. The GAP promoter is more
      appropriate than the AOX1 promoter for the B. cepacia lipase expression.
      Additionally, the recombinant lipase whose enzymatic properties were identical to
      the wild type satisfies the needs of industrial application.

PMID- 21090260
TI  - [Characterization of Cryptococcus sp. Jmudeb008 and regulation of naringinase
      activity by glucose].
AB  - OBJECTIVE: We identified a new isolated naringinase-producing yeast strain named
      as Jmudeb008, and analyzed its naringinase-producing ability cultured with
      different composition and concentration of carbon sources. METHODS: The strain
      was identified based on conventional phenotypic methods and sequences of the
      D1/D2 region of 26S rDNA and 5.8S-ITS. Media with different composition and
      concentration of carbon sources were used in shaking culture of Jmudeb008. The
      activity of naringinase was evaluated by analyzing the concentration of naringin,
      naringenin and glucose during 48 h culture. RESULTS: The Jmudeb008's sequences of
      the D1/D2 region of 26S rDNA and 5.8S-ITS were 99% identical with Cryptococcus
      laurentii. Further glucose fermentation test, urease test, DBB (diazotization
      based blue) test and nitrate reduction test were coincided with results of DNA
      sequencing. Therefore, Jmudeb008 was identified as Cryptococcus laurentii. When
      Jmudeb008 was cultured in the medium with naringin as the only carbon source, it
      could synthesize naringinase. However, when glucose was available, the synthesis
      of naringinase was repressed. CONCLUSION: The new isolated naringinase-producing
      yeast strain JmudebO08 was identified as Cryptococcus laurentii. The glucose in
      medium repressed naringinase expression.

PMID- 21090261
TI  - [Characterization of a bacterial biocontrol strain 1404 and its efficacy in
      controlling postharvest citrus anthracnose].
AB  - OBJECTIVE: Anthracnose caused by Colletotrichum gloeosporioides (Penz.) Sacc. is
      a main disease in citrus production. To develop an effective biocontrol measure
      against citrus postharvest anthracnose, we screened antagonistic microbes and
      obtained a bacterial strain 1404 from the rhizospheric soil of chili plants in
      Nanning city, Guangxi, China. The objectives of the present study were to: (1)
      identify and characterize the antagonistic bacterium; and (2) to evaluate the
      efficacy of the antagonistic strain in controlling citrus postharvest anthracnose
      disease. METHODS: Strain 1404 was identified by comparing its 16S rDNA sequence
      with related bacteria from GenBank database, as well as analyzing its
      morphological, physiological and biochemical characters. The antagonistic
      stability of the strain 1404 was determined by continuously transferring it on
      artificial media. The effect of the strain on suppressing citrus anthracnose at
      postharvest stage was tested by stab inoculation method. RESULTS: The 16S rDNA of
      strain 1404 was amplified with primers PF1 (5'-AGAGTTTGATCATGGCTCAG-3') and PR1
      (5'-TACGGTTACCTTGTTACGACTT-3') and its sequence submitted to GenBank (accession
      number: GU361113). Strain 1404 clustered with the GenBank-derived Brevibacillus
      brevis strains in the 16S-rDNA-sequence-based phylogenetic tree at 100% bootstrap
      level. The morphological traits, physiological and biochemical characters of
      strain 1404 agreed with that of Brevibacillus brevis. Less change in the
      suppressive ability of antagonist against growth of Colletotrichum
      gloeosporioides was observed during four continuous transfers on artificial
      media. The average control efficacy of the strain was 64. 9 % against the disease
      20 days after the antagonist application. CONCLUSION: Strain 1404 was identified
      as Brevibacillus brevis based on its morphological traits, phyiological and
      biochemical characters as well as 16S rDNA sequence analysis. The antagonist was
      approved to be a promising biocontrol agent. This is the first report of
      Brevibacillus brevis as an effective antagonist against citrus postharvest
      anthracnose disease.

PMID- 21090262
TI  - [Diversity of oil-degrading bacteria isolated form the Indian Ocean sea surface].
AB  - OBJECTIVE: In order to investigate the diversity of oil-degrading bacteria in the
      surface seawater across the India Ocean, and to obtain new oil-degrading
      bacteria. METHODS: Potential oil-degrading bacteria were selected out via 1:1
      mixture of diesel and crude oil as sole carbon source. Meanwhile, the community
      structure of 13 enrichments was analyzed by polymerase chain reaction with
      denaturing gradient gel electrophoresis (PCR-DGGE). RESULTS: We obtained 51
      unique strains of 29 genera after screening via morphological, physiological,
      biochemical and 16S rRNA analyses. They mainly belonged to a and gamma
      Proteobacteria. The four genera Alcanivorax (accounting for 18%), Novosphingobium
      (10%), Marinobacter (6%) and Thalassospira (6%) were the most predominant
      bacteria. Ecological analyses showed that the bacteria had high diversity with
      Shannon-Winner index (H) of 4.57968, and distributed even with Evenness index (E)
      as 0.8664771. Then Further experiments revealed oil-degrading capability of 49
      strains. In addition, our investigation revealed oil-degrading ability of genera
      Sinomonas, Knoellia and Mesoflavibacter for the first time. DGGE fingerprint
      patterns indicated that the genus Alcanivorax was an important oil-degrading
      bacteria in the surface seawater across the India Ocean. CONCLUSION: This study
      demonstrated a high diversity of the oil-degradation bacteria in the surface
      seawater of Indian Ocean, these bacteria are of potential in bioremediation of
      marine oil pollution.

PMID- 21090263
TI  - [Effects of S-layer proteins from lactobacillus against Salmonella typhimurium
      adhesion and invasion on Caco-2 cells].
AB  - OBJECTIVE: S-layer proteins of Lactobacillus acidophilus were extracted and
      purified, then the effect of Lactobacillus acidophilus and its S-layer proteins
      against the adhesion and invasion of salmonella typhimurium to caco-2 cells were
      investigated. METHODS: S-layer proteins were purified by anion-exchange column
      {diethylaminoethyl (DEAE) DE52}, and the inhibition of Lactobacillus acidophilus
      and its S-layer proteins were studied against the adhesion and invasion of
      salmonella typhimurium on Caco-2 cells. RESULTS: S-layer proteins exhibited
      strongly inhibitory effects of adhesive and invading properties of Salmonella
      typhimurium. In the adhesive experiments (competitive, exclusive and
      displacement), Salmonella typhimurium adhesion was reduced by S-layer proteins
      and the ability of adherence to Caco-2 cells were 1.17% +/- 5.97%, 8.71% +/-
      1.36% and 10.56% +/- 0.92%, respectively (P < 0.01). The influence to inhibit the
      competitive adhesion of Salmonella typhimurium was optimal. Furthermore, the S
      layer proteins showed a stronger effect than Lactobacillus acidophilus to inhibit
      Salmonella typhimurium adhesion on Caco-2 monolayers (P < 0.01). Moreover,
      invasion of Salmonella typhimurium to Caco-2 monolayers was inhibited by S-layer
      proteins. CONCLUSION: S-layer proteins inhibited adherence and invasion of
      Salmonella typhimurium. The result can merit a highlight for preventive or
      probiotic therapy in human or animals with disease caused by Salmonella
      typhimurium.

PMID- 21090264
TI  - [Colonization and distribution of recombinant Lactobacillus casei with green
      fluorescent protein in mice intestine].
AB  - OBJECTIVE: We studied the colonization ability and the distribution of the
      recombinant Lactobacillus casei in mouse intestine. METHODS: We used Green
      fluorescent protein (GFP) gene as reporter in constructing the recombinant
      plasmid pLA-GFP,which was electrotransformed into the host cells L. casei. Six
      week-old female SPF BALB/c mice were orally fed with the recombinant L. casei of
      approximately 10(9). Groups of at least three mice per condition were killed at
      1. 5 h, 3 h, 12 h, 1 d, 3 d, 5 d, 6 d, 7 d,and its duodenum, jejunum, ileum,
      caecum intestinal tract rinse solution was sampled separately. The recombinant
      bacteriain intestinal tracts were examined by plate culture count. RESULTS: The
      molecular weight of the recombinant protein was about 69 kDa in the result of
      western blot. The GFP fusion protein on the cell surface was confirmed by
      fluorescence microscopy and flow cytometric analysis. A portion of the
      recombinant L. casei was able to adhere and colonize in different regions of
      murine intestinal tract, and the planting peak was appeared on day 6
      postinoculation. The ratio of the seventh day to the first day of the recombinant
      L. casei adhered to the intestinal mucosa in the duodenum,jejunum, ileum, and
      caecum was 16.49%, 25.08%, 47.71%, and 41.03%, respectively. CONCLUSION: The
      recombinant L. casei stably expressing GFP could colonize mouse intestine. The
      field planting rule was ileum > caecum > jejunum > duodenum. Our findings
      indicated that L. casei used as a deliver vector in oral vaccine is feasible, but
      the impact on intestinal immune mechanism in mice is needed more research.

PMID- 21090265
TI  - [Immunogenicity and protective efficacy of pertactin recombinants against
      Bordetella bronchiseptica challenge].
AB  - OBJECTIVE: In this study we showed the immunogenicity and protective efficacy of
      five pertactin recombinants against Bordetella bronchiseptica (Bb) challenge.
      METHODS AND RESULTS: The complete coding sequence (2040 bp) of the prn gene (PRN)
      and its fragments,5'-terminal 1173 bp fragment (PN),3'-terminal 867 bp fragment
      (PC), two copies of region I (654 bp; PR I) in PN, and 2 copies of region II (678
      bp; PR II) in PC, were separately cloned into the prokaryotic expression vector
      pGEX-KG, and expressed in the Eschierichia coli BL21 (DE3) using induction by
      isopropyl-beta-D-thiogalactopyranoside. The recombinant proteins were named GST
      PRN, GST-PN, GST-PC, GST-2PR I and GST-2PR II. All five recombinant proteins
      showed immunological reactivity in the Western-blot analysis. Mice, immunized
      subcutaneously with two doses of the purified proteins mixed with an equal volume
      of Freund's adjuvant,produced robust PRN-specific IgG antibody levels. When
      challenged, 6 of 9 mice in GST-2PR I group and all 9 mice in the other groups
      survived intranasal challenge with three times the 50% lethal dose (LD50) of
      virulent Bb HH0809. After challenge with 10 LD50 7/9,3/9,6/9,1/10 and 6/10 of the
      mice survived. Furthermore, complete protection against intraperitoneal (i.p.)
      challenge with 10 LD50 of HH0809 was observed in mice that were injected i.p.
      with 0.5 ml rabbit anti-GST-PRN, GST-PN,GST-PC or GST-2PR II serum. Only 1 of 10
      mice survived in the group of mice that received anti-GST-2PR I, and no survivors
      were noted in the group of mice that received PRN-absorbed rabbit antiserum
      (0/5). CONCLUSION: In this study,we showed that all of five pertactin
      recombinants had differential immunogenicity and protective efficacy against Bb
      challenge. Mice immunized with GST-PC had better survival against fatal Bb
      challenge than did those immunized with GST-PN. In addition, GST-2PR II and GST
      2PR I provided the similar results These data may have implications for the
      development of safe and efficacious subunit vaccines for the prevention of
      bordetellosis on the basis of these five pertactin recombinants.

PMID- 21090266
TI  - [Identification of exotoxin-specific motifs/domains in bacterial exotoxin
      sequences and corresponding gene ontology analysis].
AB  - OBJECTIVE: To identify the exotoxin-specific motifs/domains in bacterial exotoxin
      sequences, and to expand understanding of bacterial exotoxins pathogenic
      mechanisms. METHODS: We constructed a non-pathogenic bacterial proteins database
      and collected 89 bacterial exotoxin sequences from Virulence factor database
      (VFDB), then we analyzed these protein sequences by motif/domain search using
      InterProScan (www.ebi.ac.uk/Tools/InterProScan/). RESULTS: We identified 39
      exotoxin-specific motifs/domains in 89 bacterial exotoxin sequences. CONCLUSION:
      The identified exotoxin-specific motifs/domains were closely related to the
      functions of the exotoxins and could be used as template to search for new
      exotoxins by mining pathogenic bacterial genomes. The analysis of the acquired
      Gene Ontology (GO) items was to further expend our understanding of bacterial
      exotoxin pathogenic mechanisms.

PMID- 21090267
TI  - [Construction of Escherichia coli-Streptomyces shuttle expression plasmid pMF].
AB  - OBJECTIVE: To construct an E. coli-streptomyces shuttle vector pMF that can
      integrate into the genome of streptomyces by site-specific integration. METHODS:
      We inserted the integrase gene phiC31 int and attP site into pLSB2, a suicidal
      streptomyces plasmid. The resulting conjugably transferable vector which contains
      the activator promoter system act II-ORF4/Pact I from Strepromyces coelicolor A3
      (2) could be integrated into the genome of streptomyces by site-specific
      integration. RESULTS: The plasmid pMF was conjugably transferred with high
      frequency into S. coelicolor M145, S. lividans TK24 and Saccharopolyspora
      erythraea 2338 from E. coll. Southern blotting results showed that pMF was able
      to integrate into the genome of streptomyces. We also confirmed functional
      protein expression by cloning a putative S-adenosylmethionine synthetase (SAM-s)
      gene from Sacc. spinosa S08-4 into pMF and conjugated into S. coelicolor M145.
      Protein expression were confirmed using Western blotting. CONCLUSION: pMF can be
      used as an effective tool for site-specific integration expression of foreign
      gene in streptomyces.

PMID- 21090268
TI  - [Expression and bioactivity assay of mature chicken interleukin-18 protein mutant
      using Pichia pastoris expression system].
AB  - OBJECTIVE: We expressed mature chicken interleukin-18 (mChIL-18) in Pichia
      pastoris. METHODS: The mChIL-18 gen was reconstructed by using site-specific
      mutagenesis based on the Pichia pastoris-preferred codons. The recombinant
      plasmid pPIC9K/mChIL-18 was constructed and transformed to Pichia pastoris GS115
      by electroperation. Multi-copy recombinant strains were screened by Geneticin
      (G418). The expression of mChIL-18 protein was induced by methanol. SDS-PAGE and
      Western-blot were used to analyze the expressed products. The bioactivity of
      mChIL-18 was measured by methyl thiazolyl tetrazolium assays and chicken embryo
      fibroblasts-vesicular stomatitis virus (CEF-VSV) system. RESULTS: The protein of
      mChIL-18 could be secreted by GS115. The optimum expression conditions, a rate of
      480 mg/L,were obtained as follows:temperature 28 degrees C, pH 6.5, methanol
      concentration 2% and expression time 120 h. The obtained mChIL-18 protein could
      stimulate T lymphocytes proliferation. IFN-gamma induced by mChIL-18 could
      directly inhibit the growth of VSV in CEF,and its antiviral activity was about
      1.7 x 10(4) U/mL which was produced by 400 microg/L of mChIL-18. CONCLUSION: The
      high expression of bioactive recombinant mature chicken interleukin-18 (mChiL-18)
      in Pichia pastoris had been achieved.

PMID- 21090269
TI  - [Full-length cDNA sequence analysis of avian leukosis viruses subgroup J isolated
      from chickens with clinical hemangioma].
AB  - OBJECTIVE: To understand the molecular characteristics of subgroup J Avian
      Leukosis Viruses (ALV-J) isolated from chickens with clinical hemangioma, as well
      as to get more information for controlling the spread of ALV-J in layer chickens
      flocks. METHOD: We amplified the full-length viral cDNA sequences of three layers
      isolates associated with simple hemangioma or coexisting of hemangioma and
      myeloid leukosis (ML) by PCR. We also obtained some partial sequences of three
      layer isolates related to hemangioma and one layer isolate from ML case. Then we
      analyzed and compared the sequences by using DNAstar software. RESULTS: The
      phylogentic analysis showed the significant differences in the complete sequences
      between isolates from layer hemangioma cases and from broilers, which were
      grouped to two branches in the phylogenetic tree. We noted a special 19bp
      insertion mutation in Primer Binding Site (PBS)-Leader sequences in both JS09GY3
      and JS09GY6 isolates from layer chickens with hemangioma and ML, which sequence
      was same to Rous Associated Virus type 1 (RAV-1), Rous Associated Virus type 2
      (RAV-2) and Rous sarcoma virus (strain Schmidt-Ruppin B) (RSV-SRB). In addition,
      different continuous sequences deletions were found in the U3 regions of NHH and
      JS09GY5. By motif analysis, we found some distinct motifs including c-Est-1,
      TCF11 and C/EBP only in the isolates from layers with hemangioma. The five
      isolates associated with layer hemangioma exhibited intact E element sequences
      but almost identical substantial deletion was found in all Chinese broiler
      isolates. An 11bp continuous nucleotide insertion in the E element of JS09GY3 was
      found. CONCLUSION: Isolates from layer showing hemangioma and broilers exhibited
      evident difference. We found some special mutation sites in U3, DR1 and the E
      element showed some potential relationship with the host breeds and the tumor
      phenotype, which function needs to be investigated in future. The isolates from
      layer cases with coexisting of hemangioma and ML were the recombinants of ALV-J
      and other retroviruses.

PMID- 21090270
TI  - [The countries in the Americas are mobilizing to lessen hypertension and
      cardiovascular diseases thru the reduction of salt intake in the community].

PMID- 21090271
TI  - [Breastfeeding, complimentary feeding practices and childhood malnutrition in the
      Bolivian Andes].
AB  - Northern Potosi is one of the poorest parts of Bolivia with the highest
      indicators of rural poverty, malnutrition and food insecurity in the Bolivian
      Andes. The objective of this research was to characterize the levels of
      malnutrition and describe infant feeding practices in Potosi, Bolivia and use
      this information to develop an effective, gender sensitive and culturally
      relevant intervention encouraging good infant feeding practices. Standard methods
      were used to collect anthropometric data. Weight and height data were collected
      for 400 children under five years of age from 30 communities. In six of these
      communities, interviews and focus group discussions were conducted with 33
      mothers and other families in addition to household observational data that were
      collected to describe infant feeding practices. Nearly 20% of children were
      underweight; stunting was widespread as well. 38% of mothers initiated
      breastfeeding 12 hours or more after birth. 39% of mothers initiated
      complementary feeding in the first three months following birth. The type of
      complementary food given to children was usually inadequate. With this research
      we could see that nutritional deficiencies often begin when the mother starts
      breastfeeding and when first introduced complementary feeding. Interventions
      aimed at improving maternal and child nutrition will require changes in parents'
      behavior, greater recognition and community support of the importance of child
      feeding, and the inclusion of strategies to reach young people, involve men, and
      make high quality nutrition promotion more widely available in the communities.

PMID- 21090272
TI  - [Factors related to birth weight: a comparison of related factors between
      newborns of Spanish and Colombian immigrant women in Spain].
AB  - The objective of this study is to establish differentials in birth weight (BW)
      and related factors, in term newborns (NB) of Spanish (SP) and Colombian (CO)
      immigrant mothers living in Spain, between 2001-2005. Data on the NB population
      of SP and CO mothers was retrieved from the National Statistical Bulletin of
      Birth in Spain. We analysed the association with BW (Low birth weight -LBW-
      insufficient weight -IW- macrosomia), by the nationality of the mother; taking
      into account variables such as the intergenesic interval, maternal age, number of
      live children, maternal occupation and sex of NB. The analysis was based on
      frequencies and the estimation of simple and adjusted odds ratios (OR) by means
      of logistic regression with 95% confidence intervals (95% CI). A higher
      prevalence of LBW was found in SP mothers (3.4%) than in their CO counterparts
      (2.1%). In SP mothers a higher risk of LBW (aOR 1.89, 950% CI 1.65- 2.16) and IW
      (aOR 1.49, 95% CI 1.51- 1.57) was observed. In CO mothers a higher percentage of
      macrosomia was found (8.0%). Also, a higher percentage of LBW was observed in
      female new borns (SP4.1%; CO 2.7%) as well as IW (PI (SP 25.6%; CO 19.6%) (p <
      0.001). Mothers aged > 40 years and having 4 or more children were associated
      with LBW in both nationalities. As a conclusion, NB of Colombian mothers
      presented a lower prevalence of LBW and IW, which could be explained by the
      healthy migrant effect.

PMID- 21090273
TI  - [Eating characteristics of Chilean indigenous and non-indigenous adolescent
      girls].
AB  - During childhood and adolescence, eating habits become established which are
      instrumental in determining eating behavior later in life. Various authors have
      described the acculturation of the Mapuche people toward Western culture. The
      objective of this study was to analyze the eating characteristics of indigenous
      and non-indigenous adolescent girls in the Araucania Region of Chile. A cross
      sectional design was used with a probabilistic sample of 281 adolescents
      comprised of 139 indigenous and 142 non-indigenous girls attending 168 elementary
      schools. A modified food frequency questionnaire was applied, designed to obtain
      information about eating habits and consumption of Mapuche foods. The eating
      schedules are similar in both ethnic groups, with dinner being the meal that is
      least consumed. Total snack consumption per week has a mean of 7 with an
      interquartile range (IQR) of 5 to 10 without any differences between ethnic
      groups; of these snacks, only 2 were healthy (IQR = 1 to 3). The indigenous girls
      had a higher probability of consumption of native foods including mote (boiled
      wheat) (OR = 2.00; IC = 0.93-4.29), muday (fermented cereal alcohol) (OR = 3.45;
      IC = 1.90-6.27), and yuyo (field mustard) (OR = 4.40; IC = 2.06-9.39). The
      study's conclusion is that the the eating habits and behavior of indigenous
      adolescents are similar to those of non-indigenous girls, though the former still
      consume more indigenous foods.

PMID- 21090274
TI  - [Vitamin A deficiency in preschool children of Recife, Northeast of Brazil].
AB  - The purpose of the study was to evaluate the extent of vitamin A deficiency (VAD)
      among preschool children in the city of Recife, Northeast Brazil. The sample
      comprised 344 children of both sexes, 24 to 60 months old, in 18 public day care
      centres in the city of Recife, in 2007. The nutritional status of vitamin A was
      assessed by biochemical (serum retinol) and dietetic (vitamin A rich-food
      consumption) indicators and the pondo-stature status through anthropometric
      indicators weight-for-age, height-for-age and weight-for-height. The prevalence
      of hyporetinolemia (< 0.70 micromol/L) was 7.7% (IC 95% 4.88 - 11.81), which
      characterizes the VAD as a light-type public health problem, according to World
      Health Organization criteria. On the other hand, 29.6% (IC 95% 24.22 - 35.63) of
      children had acceptable or marginal levels (0.70 to 1.04 micromol/L) of retinol.
      Regarding the vitamin A rich-food intake, values below the EAR (Estimated Average
      Requirement) - 210 microg/ day for children of 1 to 3 years old and 275
      microg/day for children of 4 to 8 years old - were 8.1% and 21.3% respectively.
      The prevalence of anthropometrical deficits (< -2 scores -Z) in preschool
      children were 2.5% for the indicator weight-for-age, 8.6% for height-for-age and
      1.5% for weight-for-height. The research findings point out to the importance of
      institutionalization for the appropriate nutritional status of children and
      maintenance of adequate reserves of vitamin A. However, more studies are needed
      focusing on non-institutionalized preschool, or children living outside the
      privileged environment of public day care centres.

PMID- 21090275
TI  - [Impact of income strategies on food security in rural Mayan communities in
      northern Campeche].
AB  - This paper examines the effect of income strategies on sufficiency of caloric
      intake in Mayan domestic groups (DG) of Campeche, Mexico. The analysis was based
      on the sustainable livelihoods approach. Information was obtained through a
      survey of households (N = 237) in four communities. The results reveal that all
      of the DG have diversified income strategies with clearly defined orientations.
      The caloric sufficiency index (CSI) is different (p < 0.05) among conglomerates
      (C) of DG and increases with the increase of the proportion of agricultural
      income in relation to total income. The wage labor strategy (37.6%) corresponding
      to C1 of DG (CSI-C = 0.69) and the agriculture-wage labor strategy (42.6%; CSI-C2
      = 0.87) do not cover energy requirements of the DG. Only the agricultural
      strategy satisfies caloric intake needs (CSI-C3 = 1.09; CSI-C4 = 1.30) of the DG
      (19.8%). These results are associated with the heterogeneity of resources of the
      DG's, particularly, with the quality and extent of land, presence of producer
      organizations, and current rural policies. Implementation of differentiated local
      policies, interinstitutional coordination, and community participation could
      contribute to improving effectiveness of policies aimed at eradicating food
      insecurity.

PMID- 21090276
TI  - [Energy protein intake during nutritional recovery and nutritional status
      achieved].
AB  - Thirty years ago malnourished Chilean children were recovered by CONIN; they were
      fed ad libitum and this may have favoured the appearance of overweight-obesity
      (SP/OB). The objective of this study was to evaluate the relationship between
      energy-calorie intake during nutritional recovery and the appearance of
      overweight-obesity (SP/OB). The design was a retrospective, analytical study of
      the universe formed by the 168 clinical records found, of children below 2 years
      of age, recovered by CONIN between 1977 and 1982. Nutritional status was assessed
      using the Sempe criteria (applied in the period evaluated) and those of WHO,
      (currently in use), on admission, after 4 month treatment and on discharge. By
      Sempe criteria, malnutrition on admission was classified 25% severe, 63% moderate
      and 12% mild; instead, using WHO standards these figures were 14.9%, 29.2% y
      38.1%, respectively; the remaining children were well nourished. On discharge,
      there was no SP/OB by W/A (Sempe), but by W/H (WHO) 6% and 13.8% were SP/OB after
      3 months and on discharge, respectively. Food intake, administered ad libitum,
      reached a mean of 148 kcals/ kg/d and 4 g prot/kg/d. SP/OB children had greater
      daily weight gain (30.3 vs 19.2 g/d) than the non-obese children and greater
      daily weight gain than the mean for age and sex (19.7 vs 8.2 g/dia). The
      prescribed feeding reached values considered high by currently used criteria;
      actual intake, administered ad-libitum, was significantly lower and was
      associated with 13.8% of children with overweight-obesity at the time of
      discharge.

PMID- 21090277
TI  - [Abnormal eating behaviours are not associated with micronutrient deficiencies
      among women of childbearing age from Mexico City].
AB  - The aim of this study was to evaluate the association between the risk of
      abnormal eating behaviors (AEB) and vitamin and mineral deficiencies among women.
      Women of childbearing age (n = 282) were systematically sampled with a random
      start (21.9% adolescents) in 6 suburbs in the west side of Mexico City, they were
      non pregnant or breastfeeding. Vitamin A, C, E, B12, folic acid, hemoglobin,
      ferritin, cupper, iron and zinc concentrations were measured. A questionnaire
      validated in the Mexican population was used for screening AEB. Data were
      analyzed by descriptive statistics and by using Fisher's test. Approximately 68%
      of the sample belonged to a mid-low or lower socioeconomic status. 14% had risk
      of AEB, without statistical differences between adults and teenagers. 10% used
      diuretics or laxatives to reduce weight within the trimester preceding the
      survey. Vitamin E, zinc and iron were the most widespread deficiencies affecting
      47%, 44% and 27% of the population, respectively. There was no association
      between the AEB and micronutrient deficiencies neither when AEB were analyzed
      globally nor individually. Considering these results and the high prevalence of
      the AEB and overweight in this population, it is important to promote the
      adoption or healthy behaviors to achieve an adequate weight.

PMID- 21090278
TI  - [Risk-benefit of some mollusks and processed fishes in the renal patient's diet].
AB  - The renal diet must include limited amounts of high quality protein, phosphorus P
      and potassium K. n-3 polyunsaturated fatty acids (n-3PUFA EPA and DHA), present
      in fishes and mollusks, render beneficial properties against progression of renal
      damage. The aim of this study was to evaluate protein PR, phosphorus P, potassium
      K, calcium Ca and n-3PUFA in processed fishes and mollusks as an alimentary
      option for renal patients. Canned tuna (water AA and oil AC), sardine in tomate
      sauce ST and chipotle SC and smoked salmon SA, fresh jumbo flying squid CA,
      common octopus PU and oyster OS were evaluated. Significant difference was
      detected (p <.0.05) for K between different types of fish. SA contained 38g/100g
      PR, 307 mg/100g of P, 371 mg/ 100g K and 106 mg/100g n-3PUFA. Sardines contained
      (279-304 mg/100g of P and 283-322 mg/100g K and tunas 142-160 mg/100g P and 141
      154 mg/100g K. Tunas and sardines had elevated concentration of n-3PUFA (4114 and
      4790 mg/ 100g respectively), P:n-3PUFA and K:n-3PUFA ratio was low in tunas
      (0.03) and sardines (0.06). AA and AC contained (10.1 and 11.1 mgP/gPR), while ST
      and SC provided 26.4-19.1 mg/P/gPR. n-3PUFA/gPR were similar for tunas and
      sardines (302-424mg/gPR). Mollusks: CA presented the highest values of P and PR
      (2.4 mg/100g and 18.4g/100g). n-3PUFA ranged from 4.3 to 79 mg/100g in PU and OS
      respectively. Among processed fishes, only canned tunas are recommended for the
      diet of renal patients, in an individualized basis. The risk-benefit ratio of
      sardines in the renal diet should be evaluated, due to their high content of P
      and n-3PUFA. Salmon and mollusks are not recommended for the renal diet.

PMID- 21090279
TI  - [Hibiscus sabdariffa L: source of antioxidant dietary fiber].
AB  - Dietary fiber and antioxidants are food constituents and functional ingredients
      that are generally addressed separately. Nowadays there is scientific evidence
      that primary characteristics of DF assigned to non starch polysaccharides and
      lignin (resistance to digestion and absorption in the small intestine and
      fermentation in the large intestine) can be extended to other indigestible food
      constituents that are resistant to digestion and absorption in the human small
      intestine with complete or partial fermentation in the large intestine. The
      antioxidant dietary fiber concept was defined as a dietary fiber concentrate
      containing significant amounts of natural antioxidants associated with non
      digestible compounds. Hibiscus sabdariffa L flower shows in its composition an
      important percentage of dietary fiber and high antioxidant capacity. The infusion
      obtained by decoction of flowers, had been extensibility studied due to the
      healthy properties. In this work the principal nutritional aspects from Hibiscus
      sabdariffa L and its use as a possible antioxidant dietary fiber source had been
      considered.

PMID- 21090280
TI  - [Baked product development based fermented legumes and cereals for schoolchildren
      snack].
AB  - The objective of this work was to develop three foodstuffs based on mixes of
      wheat and fermented and non-fermented legumes, for the purpose of contributing
      with a healthy alternative for school snacks. To this aim, refined wheat flour
      was partially substituted with whole legume flours for the preparation of cakes,
      brownies and cookies, foodstuffs traditionally consumed by school age children.
      Cakes were formulated substituting 20% of wheat flour with Phaseolus vulgaris
      flour, brownies with 30% of Cajanus cajan flour and cookies with 30% of Vigna
      sinensis flour, using fermented and non-fermented legumes in the three products.
      When these products were subjected to sensorial evaluation through a test of
      degree of acceptability and using a hedonic scale of 7 points, values higher than
      5 in the attributes taste, color and overall appraisal were found for all the
      products. In addition, the preference was measured with a group of 90 school
      children, corroborating the results obtained at laboratory level. Chemical
      characterization showed protein contents between 12 and 13% for the cake, 10 and
      11% for the brownies and 10% for the cookies and protein digestibilities in vitro
      of 91%, 87% and 93%, respectively. The calorie supply, calculated per portion was
      of 199 kcal, 246 kcal and 237 kcal, for cakes, brownies and cookies,
      respectively. It was concluded that it is technically possible to incorporate
      fermented and non-fermented Phaseolus vulgaris, Vigna sinensis and Cajanus cajan,
      to highly consumed products such as cakes, brownies and cookies with a higher
      nutritional content and well-accepted by school-age children.

PMID- 21090281
TI  - [Tannins, phytic phosphorus, phytase activity in the seed of 12 sorghum grain
      hybrids (Sorghum bicolor (L) Moench)].
AB  - In order to evaluate the variability in concentration of secondary metabolites
      among grains from different sorghum hybrids (Sorghum bicolor (L) Moench) and
      provide some information for rational use in animal feeds, grain samples were
      collected from 12 hybrids (Criollo 1, Criollo 27, Chaguaramas III, Chaguaramas
      VII, Cristiani Burkard H-8046-2, Guanipa 95, Himeca 101, Himeca 400, Pioneer 81
      G67, Pioneer 83-G88, Pioneer 86-P42 y Tecsem 120) sowed on 2008 in the Turen
      municipality, Portuguesa State-Venezuela. Using standardized analytical methods,
      hybrids showed polyphenolics compounds contents (0.92 +/- 0.37% TaE), total (0.61
      +/- 0.29% TaE) and condensed tannins (0.95 +/- 0.65% LeuE), phytic phosphorus
      (0.17 +/- 0.03%) and intrinsic phytase activity (12.3 +/- 6.74 U/kg) in the
      ranges described in the literature, with an important variation among hybrids
      that must be considered for their inclusion levels in the formulation of balanced
      feeds, as well as plant breeding programs.

PMID- 21090282
TI  - [Preliminary study on the distribution and impact factors of methylmercury in
      surficial sediments from main mangrove wetlands of China].
AB  - Total mercury (THg), methylmercury (MeHg) and environmental factors were
      determined to study distributions of MeHg and Hg methylation in the sediments
      from 8 main mangrove areas of China. The results showed that it was not
      consistent for distributions of THg and MeHg in sediments. Concentrations of MeHg
      in sediments from Sanya, Dongzhaigang (Hainan Province), Techengdao, Leizhou,
      Gaoqiao, Futian (Guangdong Province), Daguansha (Guangxi Autonomous Region),
      Fugong (Fujian Province) were (0.24 +/- 0.04), (0.58 +/- 0.27), (0.52 +/- 0.23),
      (1.56 +/- 0.49), (0.50 +/- 0.25), (1.21 +/- 0.36), (1.86 +/- 1.04), (0.47 +/-
      0.16) ng x g(-1) respectively. There were regional difference in MeHg contents
      which decreased in the order of Daguansha > Leizhou > Futian > Dongzhaigang >
      Techengdao > Gaoqiao > Fugong > Sanya. Input of Hg and organic matter from
      industry and aquiculture may lead to high level of MeHg. Compared with sediments
      from other estuaries of the world, serious pollution of MeHg was found in
      mangrove sediments of China. (2) % MeHg in mangrove sediments ranged from 0.11%
      to 7.13%, which decreased in the order of Daguansha > Techengdao > Leizhou >
      Futian > Gaoqiao > Dongzhaigang > Sanya > Fugong. There was significantly
      positive correlation between % MeHg and sandy fraction (p < 0.05), and
      significantly negative correlation between % MeHg and silt-clay fraction (p <
      0.05). (3) Total bacteria (TB) in mangrove sediments ranged from 2.44 x 10(10) to
      1.91 x 10(11) CFU/g (dry weight), TB decreased in the order of Fugong > Sanya >
      Gaoqiao > Dongzhaigang > Futian > Daguansha. Sulfate-reducing bacterium (SRB)
      ranged from 1.73 x 10(4) to 4.92 x 10(6) CFU/g, SRB decreased in the order of
      Futian > Fugong > Dongzhaigang > Sanya > Gaoqiao > Daguansha. Wastewater with
      high organic matters leads to high SRB. The types of surface sediments also had a
      great impact on the amount of SRB. There was no significant correlation among
      MeHg and environmental factors, which indicated that exogenous input is the main
      cause of MeHg pollution in mangrove sediments.

PMID- 21090283
TI  - [Response of phytolith in Leymus chinensis to the simulation of global warming
      and nitrogen deposition on Songnen grassland, China].
AB  - Using infrared radiator and applying nitrogen on Leymus chinensis community on
      Songnen grassland to simulate global warming and nitrogen deposition, phytolith
      was extracted from L. chinensis, the morphology and content of phytolith were
      analyzed. Phytolith in L. chinensis were classified into 4 main classes and 12
      subclasses, as well as some small phytolith fragments. Of all the phytolith
      types, the hat-shaped take as much as 70%. The hat-shaped with spire and hat
      shaped with flat peak may have different growth mechanisms from the echinate hat
      shaped, and the point-shaped phytolith is more sensitive to N deposition.
      Compared with control check (CK), the warming treatment seemed to promote the
      growth of phytolith (increased the length and width 0.1-2.6 microm), while the N
      deposition treatment had an effect of inhibition on the growth of phytolith
      (decreased the length and width 0.1-1.4 microm), and when warming and N
      deposition mixed, in this treatment the effect of inhibition caused by N
      deposition declined. Hollow elongate (46% of elongate) was observed only in N
      deposition treatment, and the content of other types (elongate, point-shaped, hat
      shaped excluded) increased to 10%, it was supposed, as L. chinensis is the
      dominant species in Songnen grassland, the effect of N deposition might be more
      significant than warming on such grassland, and warming could mitigate the
      affection of N deposition. Phytolith was sensitive to the change of environmental
      factors, this study provided an experimental evidence for phytolith as a reliable
      proxy indicator for paleo-environment.

PMID- 21090284
TI  - [Leaf nitrogen and phosphorus stoichiometry in typical desert and desertified
      regions, north China].
AB  - Characteristics of leaf nitrogen and phosphorus stoichiometry at regional scale
      is key factors to understand spatial pattern, forecast change trends and reveal
      responses of terrestrial ecosystem to global change. In this study, pattern of
      leaf nitrogen and phosphorus of 214 plants was investigated to elucidate their
      relationships with rainfall and temperature in typical desert and desertified
      regions of northern China. The results showed that average leaf nitrogen
      concentration, average leaf phosphorus concentrations, and leaf N/P of 214
      species are (24.45 +/- 8.1) mg/g, (1.74 +/- 0. 88) mg/g, 15.77 +/- 7.5 in these
      regions of northern China, respectively. Compared with other studies at global,
      national or regional scale, leaf nitrogen and phosphorus concentrations are
      significantly higher in this study (p < 0.001). However, leaf N/P didn't show any
      significant differences with other studies. This implies that leaf N/P is
      generally well-constrained. One-way ANOVA analysis showed that leaf N, P, and N/P
      varied significantly among trees, shrubs, graminoids, and forbs. Leaf N
      concentration in shrubs, forbs and leaf P concentration in forbs are averagely
      higher than those in other life-forms, respectively. This implies that nutrient
      use strategies are significantly different among plant life-forms. There are no
      significant differences in leaf nitrogen concentration among each typically
      desert and desertified region. However, Leaf phosphorus concentration and leaf
      N/P are significantly different among each typically desert and desertified
      regions. Leaf phosphorus concentrations are relatively high in Kerqin Sand Land
      and Mowuso Sand Land. Leaf N/P of most species in Talimu basin, Zhunger Basin,
      and Alashan is higher than 16, and lower than 14 of most species in Kerqin Sand
      land. This means that nutrient constraining in different regions varies greatly.
      Correlations analysis showed that leaf N, P, and N/P are significantly correlated
      with annual precipitation, but not significantly correlated with annual mean
      temperature in desert and desertified regions of northern China.

PMID- 21090285
TI  - [Effects of simulated nitrogen deposition on soil respiration in northern
      subtropical deciduous broad-leaved forest].
AB  - To investigate the effects of elevated nitrogen deposition on forest soil
      respiration, a simulated nitrogen deposition field experiment was conducted in
      northern subtropical deciduous broad-leave forest from April 2008 to April 2009.
      Nitrogen treatments included the control (no N addition, CK), low-N [50 kg x (hm2
      x a)(-1), T(L)], medium-N [100 kg x (hm2 x a)(-1), T(M)], and high-N [150 kg x
      (hm2 x a)(-1), T(H)]. The respiration rates were measured by a static chamber-gas
      chromatograph method. Results showed that nitrogen deposition did not change the
      seasonal and daily variation patterns of soil respiration. Compared to the
      control, T(L), T(M) and T(H) treatments reduced soil annual average respiration
      rates by 8.51%, 9.74% and 11.24%, respectively. Meanwhile, T(L), T(M) and T(H)
      treatments decreased daily average soil respiration rates by 4.42%, 11.09% and
      12.17%, respectively. Significant relationship was found between soil respiration
      rate and soil temperature. The Q10 (temperature sensitivity coefficients) for
      soil respiration of CK, T(L), T(M), and T(H) treatments were 2.53, 3.22, 2.64 and
      2.92, respectively. Our findings suggested that nitrogen deposition reduced soil
      respiration, and increased soil respiration temperature sensitivity in northern
      subtropical deciduous broad-leave forest.

PMID- 21090286
TI  - [Impact of land use change and cultivation measures on soil organic carbon (SOC)
      and its 13C values].
AB  - In Quzhou County, Hebei Province where now intensive farming system is operated,
      original grassland and farming land under different tillage, crop straw return
      and fertilization measures were studied using isotope carbon for the analysis of
      the impact on soil organic carbon (SOC) properties. The research indicated that
      after change into farmland (34 years), SOC is significantly reduced and for 1 m
      of soil layer, the scope of reduction is from 13.3%-35% and this decrease happens
      in 0-40 cm of soil layer. After 8 years of fertilization, SOC can be increased at
      0.83 g x kg(-1). No-tillage can significantly increase the SOC especially in 0-10
      cm but plough will increase the SOC at 10-15 cm and 15-20 cm. Change of delta13 C
      of SOC due to land use change mainly happens in 0-20 cm, where input of organic
      materials from maize stored. In soil layer of 0-5 cm, only maximum 18% of SOC is
      from crop residues and in 15-20 cm, this percentage is about 5%.

PMID- 21090287
TI  - [Magnetic characters of river sediment of urban area in Lanzhou].
AB  - A total of 23 deposits samples were collected from 8 selected the river sediments
      in Lanzhou urban area as researching objects of magnetic property and organic
      matter measure. The results indicate that: (1) the magnetic property controlled
      by magnetite which is ferrimagnetic mineral, and anti-ferromagnetic component
      such as hematite and goethite; (2) the value of samples' magnetic parameters
      (such as: chi, SIRM, magnetic hysteresis loops and M-T curves) increased from
      upstream to downstream in Paihong River, Shier River and Yuer River, Shuimo
      River; decreased in Qili River and Lanni River; and contrasting above-mentioned,
      the value of samples' magnetic parameters were low in Luoguo River and Dasha
      River. Based on the variation of magnetic parameters, such as chiFD, chiARM,
      chiFD/Ms and chiARM/Ms, we divided the rivers into three groups according to the
      contribution originating from anthropogenic activities into spatial river
      sediments: first type, such as Paihong River, Shier River, Yuer River and Shuimo
      River, called downstream concentrate type; second type, such as Qili River and
      Lanni River, called upstream concentrate type; third type, such as Luoguo River
      and Dasha River, called less affected type. Bulk samples also demonstrate a
      strong linear positive correlation between magnetic parameters chiFD, chiARM and
      the content of organic matter, which reflected the content of superparamagnetic
      and single domain grains were nice proxy parameters of the content of organic
      matter of river sediments.

PMID- 21090288
TI  - [In situ measurement of atmospheric HCFC-22 at the Shangdianzi GAW regional
      station].
AB  - An in situ GC-ECD monitoring system was established at the Shangdianzi GAW
      Regional station from April 2007 to March 2008, and the mixing ratio of
      atmospheric HCFC-22 was (278.1 +/- 113.6) x 10(-12) (mol/mol). A "R" statistical
      software was applied to the HCFC-22 time series to separate background and
      pollution data. The background HCFC-22 mixing ratio was (199.5 +/- 5.1) x 10(
      12), close to northern hemisphere background level observed at Mace Head and
      Trinidad Head stations. The pollution HCFC-22 mixing ratio was (312.1 +/- 121.0)
      x 10(-12) due to anthropogenic emission from various regions and air mass
      transport. There was no significant seasonal variability of background data.
      However, pollution data was much higher in summer than that in winter, and
      elevated up to 100.9 x 10(-12) in July than in January attribute to seasonal
      emission characteristics. The mean HCFC-22 mixing ratio from southwest wind
      sector (327.3 x 10(-12)) was much higher than that of northeast sector (236.2 x
      10(-12)). The W-WSW-SW wind sector has a positive contribution to the HCFC-22
      level, while NNE-N-NE has a large negative contribution.

PMID- 21090289
TI  - [Characteristics and influencing factors of carbonaceous aerosols in PM2.5 in
      Shanghai, China].
AB  - Organic carbon (OC) and elemental carbon (EC) in PM2.5 samples collected in urban
      (Xujiahui) and industrial (Baoshan) areas in Shanghai during 2007-2008 were
      analyzed with a DRI carbon analyzer using IMPROVE-TOR protocol. The results
      showed that the seasonal average concentrations of OC and EC were highest in the
      winter and lowest in the summer. The annual average concentrations of OC and EC
      were 8.10 and 3.91 microg x m(-3) at the urban sampling site, and 11.91 and 4.69
      microg x m(-3) in the industrial area. The annual average OC/EC ratios at the two
      sites were 2.01 and 2.42, respectively. Strong correlations (R2 0.52-0.87)
      between OC and EC were found in all seasons, with the highest correlation
      coefficients in the winter ( R2 0.87 and 0.80) and the lowest in the spring (R2
      0.52 and 0.58), indicating that the pollutant sources in spring was more
      complicated due to the varying wind directions. The annual average concentrations
      of secondary organic carbon (SOC) were 2.72 and 5.07 microg x m(-3) at the urban
      and industrial sites, accounting for about 30% of the total OC. The contribution
      of SOC to OC was the highest (about 40%) in the summer, in accordance with the
      high temperature and strong solar radiation in the summer. It was also found that
      precipitation had significant impact on the concentrations of OC and EC,
      especially in the winter. The average concentrations during periods without
      precipitation were two times higher than that during periods with precipitation
      in the winter, whereas no significant difference was found between the
      concentrations of OC and EC in the periods with and without precipitation in the
      summer, possibly due to the more stable atmospheric conditions during the periods
      with precipitation in comparison with those without precipitation. The OC/EC and
      SOC/OC ratios decreased significantly during precipitation.

PMID- 21090290
TI  - [Observational study of formaldehyde in air, rain and fog water at a site on the
      Mangdang Mountain of Fujian, China].
AB  - Through 2,4-dinitrophenylhydrazine (DNPH) high-performance liquid chromatography
      (HPLC) method, the levels of formaldehyde in ambient air, rain and fog samples
      were measured in Mangdang Mountain, Fujian Province, from March to April 2009.
      The average concentrations of formaldehyde in ambient air, rain and fog are 4.0 x
      10(-10), 2.19 micromol/L and 2.94 micromol/L, respectively. Based on previous
      researches, this study described formaldehyde hydrolysis and reacting with S(IV)
      and other chemical reaction processes in liquid phase, explaining the phenomenon
      that the solubility of formaldehyde in the liquid phase is higher than the
      theoretical value. On-site measured Henry coefficients (Hme) and the effective
      Henry coefficients (H*) were derived from concentration of formaldehyde in
      ambient air, rain and fog samples and references. Comparing Hme and H*, this
      study found that the measured liquid phase concentrations of formaldehyde are
      higher than the theoretical concentrations, consistent with the references. The
      further founding is that Hme/H* in fog is higher than in rain, proving the result
      of Mangdang Mountain that the concentration of formaldehyde in fog is higher than
      in rain. Considering the climatic characteristics of Mangdang Mountain in spring,
      the wet deposition of formaldehyde is an important way in this area.

PMID- 21090291
TI  - [Inversion formula of one-dimensional water quality equation for the export loads
      of nonpoint sources pollution in headwater area].
AB  - An inversion formula for the export loads of nonpoint sources pollution in
      headwater area was established based on one-dimensional water quality equation,
      and it was used to calculate the pollution loads for tributaries in the headwater
      catchment of Laohutan Reservoir, in Huzhou City, Zhejiang Province of China.
      Monte Carlo method was adopted to determine the sensitivity about each input
      parameter in the inversion formula. Because each sensitive parameter can be
      measured directly in the inversion formula, so that this approach can decreased
      calculation error, which is often caused by the parameter estimation.
      Furthermore, the inversion formula can be adopted to calculate pollution loading
      on any time scale. Monthly nonpoint sources pollution export loads in 2007 were
      calculated by the model in the research catchment. Results showed that pollution
      loads in stream were significantly positive related with flow rates (r > 0. 90, p
      < 0.01), and the flow rate was the most sensitive factor in the model, followed
      by the nutrient concentration and background concentration at the stream end.
      While, comprehensive degradation coefficient and flow velocity contributed very
      little influence to the model uncertainty.

PMID- 21090292
TI  - [Relationship between landscape pattern and river water quality in Wujingang
      region, Taihu Lake watershed].
AB  - Wujingang region was taken as the study area to explore the relationship between
      landscape pattern and river water quality. Remote sensing image was interpreted
      and buffer zones were constructed, and then landscape patterns characterized by
      land-use patterns and five selected landscape metrics including Number of patches
      (NP), Area-weighted mean patch fractal dimension (FRAC _AM), Shannon's diversity
      index (SHDI), Shannon' s evenness index (SHEI), Contagion index (CONTAG) in each
      buffer zone were obtained. By employing the correlation analysis between the
      landscape pattern and river water quality, the results indicated that the river
      water quality was influenced by landscape pattern. The percentage of built-up
      area was positively related with water quality indicators, demonstrating that the
      percentage of built-up area was one of the key factors affecting the river water
      quality, while the percentage of cultivated land showed a negative relationship.
      Furthermore, the relationships between the selected five landscape metrics and
      water quality were also revealed. SHDI and SHEI were significantly positively
      related with water quality indicators, while CONTAG showed the opposite
      relationship.

PMID- 21090293
TI  - [Strategy of grain yield stability cooperated with harmonious water environment
      quality of small agricultural watershed].
AB  - This paper investigated the spatial variability of the correlations between grain
      yields and fertilization quantity within the selected agricultural watershed, in
      the typical black soil region, and then optimized the fertilization quantity at
      different landscape farmlands within the watershed based on the regression
      equations. Study simulated the surface runoff water quality before and after
      fertilization spatial adjustment with the achieved parameters by Soil and Water
      Assessment Tool (SWAT) model. The results showed that watershed scale
      fertilization adjustment is possible and necessary according to the spatial
      heterogeneity about fertilization and grain yields. Based on grain yield
      stability, spatial adjustment of fertilization reduced the whole watershed total
      N fertilization quantity by 1.88%, and the total non-point nutrients load
      reduction of NH4+ -N and NO3- -N was 9.7%, 5.6%, respectively.

PMID- 21090294
TI  - [Selection of winter plant species for wetlands constructed as sewage treatment
      systems and evaluation of their wastewater purification potentials].
AB  - In order to establish an evaluation system for selection of winter wetland plants
      possessing high wastewater purification potentials in subtropics areas, designed
      sewage treatment experiments were carried out by introducing into the constructed
      wetlands 25 species of winter wetland plants. Cluster analysis was performed by
      including harmful environment-resistant enzyme and substrate enzyme activities
      into the commonly applied plant screening and assessment indexes system. The
      obtained results indicated that there were significant differences among the
      tested winter plants in their root length and vigor, leaf malonaldehyde (MDA),
      biomass, average nitrogen and phosphorus concentration and uptake, and urease and
      phosphoric acid enzyme activities in the root areas. Based on the established
      evaluation system, the tested plants were clustered into 3 groups. The plants in
      the 1st group possessing high purification potentials are Oenanthe javanica,
      Brassicacapestris, Juncus effusu, Saxifragaceae, Iris pseudoacorus, Osmanthus
      fragrans and Iris ensata; those in the 2nd group possessing moderate purification
      potentials are Brassica oleracea var acephala, Calendula officinalis, Aucuba
      japonica, Ligustrum lucidu, Beta vulgaris, Rhododendron simsii and Ilex
      latifolia; and those in the 3rd group with low purification potentials are
      Brassica oleracea var acephala, Calistephus chinensis, Rosa chinensis,
      Antirrhinums, Liriope palatyphylla, Zephyranthes candida, Fatshedera lizei,
      Petunia hybrida, Ilex quihoui, Dianthus caryophyllus and Loropetalum chinensis.

PMID- 21090295
TI  - [Influence of intermittent sediment disturbance-sedimentation process on the
      bioavailable phosphorus in standing water].
AB  - The course of intermittent sediment disturbance-sedimentation, that sediment
      disturbance was for 10 min and succeeding sedimentation was for 1430 min each day
      over a 17-day period, was simulated to investigate the variation of bioavailable
      phosphorus (BAP) in overlying water. The results showed that the concentrations
      of BAP increased obviously at Oh after each disturbance, and the maximum
      concentration of BAP was reached up to 2.82 mg x L(-1) after 1 d (the first
      disturbance). However, the BAP gradually decreased with the sedimentation time
      increase (1 h, 6 h, 24 h). Moreover, at 0, 1, 6, 24 h after disturbance, the BAP
      gradually declined with the number of sediment disturbance increase, but the BAP
      at Oh after each disturbance was higher than that at 1 h, 6 h, 24 h. This may be
      attributed to the immediate release of bioavailable particulate phosphorus (
      BAPP), as a result of sediment disturbance. The average BAPP/BAP was up to 95.0%
      at Oh after disturbance over a 17-day period, but this value gradually decreased
      with the sedimentation time increase (1 h, 6 h, 24 h). At 0 h, 1 h, 6 h, 24 h
      after each disturbance, the equilibrium concentrations of total dissolved
      phosphorus (TDP) were reached after 5 d (0.053, 0.062, 0.051, 0.045 mg x L(-1)),
      and the percentage of TDP in BAP also decreased gradually. Therefore, it is
      considered that sediment intermittent disturbance can accelerate the
      transformation from TDP to PP and hinder the development process of
      eutrophication in standing water. Sequential fractionation also indicates that
      the percentage of refractory phosphorus in Tot-P increased from 72.8% (raw
      sediments) to 77.3% (sediments after disturbance), attributable to the increase
      of concentrations of occluded Fe/Al-P. It is hopefully suggested an acceleration
      of transformation of phosphorus from mobile fractions to refractory fractions.

PMID- 21090296
TI  - [Comparison of H2O2 and UV processes on the inactivation efficiency of
      Microcystic aeruginosa].
AB  - Setting Microcystic aeruginosa as study subject, the inactivation efficiency and
      its effect on photosynthetic activity by H2O2 and UV processes were investigated.
      The results showed that the inactivating efficiency increased with H2O2 dosage in
      the range of 0-2 mmol x L(-1), and the photosynthetic activity decreased with it
      gradually, but the efficiency wasn't enhanced when the dosage exceeded 2 mmoL x
      L(-1). The inactivation by UV process was high. Under the algae concentration of
      35 x 10(8) cells/L, UV dosage of 91.8 mJ/cm2 was enough to inhibit its growth by
      7d; UV process was superior to H2O2 in terms of photosynthetic activity, also the
      parameters could be fitted exponentially well; To guarantee high removal of
      algae, H2O2 must be dosed excessively, so UV254 of algae solution would be higher
      than that of UV process.

PMID- 21090297
TI  - [Effect of ozone-UV pretreatment on coagulation of raw water with high organic
      matter].
AB  - Humic acid as a model pollutant, this paper aims to evaluate the effect of
      ozonation, ultraviolet irradiation and ozone-UV (UltraViolet) pretreatment
      process on the coagulation performance of raw water with high organics. The
      results indicated that three kinds of pretreatment had obvious mineralization on
      soluble humic acid in the raw water, and UV and ozone-UV pretreatment had a
      strengthening effect on the later coagulation process. With the increase of
      adding ozone dose and extension of UV irradiation, a decline in both content of
      TOC and turbidity were observed. Under the ozonation pretreatment process, when
      the concentration of ozone dose (O3/C) was 9.0 mg/mg, 47% of humic acid could be
      removed by pretreatment, the content of TOC and the turbidity of the filtrated
      water was 3.5 mg/L and 2.6 NTU, respectively. With the UV pretreatment process,
      after 3 h UV irradiation, 52% of soluble organic matter could be removed by
      pretreatment, and the content of TOC and the turbidity of the filtrated water
      were 2.0 mg/L and 1.0 NTU, respectively. Furthermore, the UV/O3 combined system
      was better than separate system. The optimum in combined pretreatment process was
      that the concentration of ozone dose (O3/C) was 1.0 mg/mg, the time of UV
      irradiation was 1 h, the TOC of the filtrated water was 2. 6 mg/L and the
      turbidity of that was less than 1.0 NTU. The mineralization effect under various
      pretreatment processes was achieved by the oxidation of OH, and at the same time
      the construction of humic acid was changed by pre-oxidation. As a result, the
      stability of the Reunion construction of humic acid was reduced which promoted
      the removal of the organic matter during the coagulation process.

PMID- 21090298
TI  - [Comparative study on the coagulation of PACl with different contents of aluminum
      polymeric species].
AB  - Based on the Ferron assay of aluminum species, jar test and filterability index,
      four types of PACl products of Al(a),, Al(b), Al(c), and Al(abc) are investigated
      on raw water samples from settling tank of water plant, which denote the
      different dominant aluminum species of AlCl3 for monomer or oligomer, PACl with
      high Al13 contents for mediate polymer of Al(b), PACl with high Al(c) contents
      for aluminum high polymer or Al (OH)3 sol, and industrial PACl for the mixed
      aluminum polymeric species with variety of alkalinity of Al(a), Al(b) and Al(c),
      respectively. Multiple parameters including the residual turbidity, UV254,
      particles removal, filterability index as well as the floc formation kinetics are
      monitored to make a comprehensive evaluation of their coagulation and settling
      filtration performance. It indicates that PACl with high Al(b) contents
      demonstrate their predominant ability in the turbidity removal, whereas PACl with
      high Al(c) contents prefer to cutting down the particles and UV254.

PMID- 21090299
TI  - [Comparison of heterotrophic nitrification and aerobic denitrification system by
      strain qy37 and its accelerating removal characteristic of NH4+ -N].
AB  - The characterization in nitrogen removal of a heterotrophic nitrification-aerobic
      denitrification bacteria (qy37) was studied. A strain coded as qy37 which had
      simultaneous heterotrophic nitrifying and aerobic denitrifying ability was
      screened. In the light of its morphological and physiological characters as well
      as their sequence analysis of the 16S rDNA, strain qy37 was identified as
      Pseudomonas sp.. In heterotrophic nitrifying system utilized ammonium chloride as
      nitrogen source, the concentration of NH4+ -N reduced from 138.52 mg/L to 7.88
      mg/L and COD reduced from 2408.39 to 1177.49 mg/L by strain qy37 in 32 hours, the
      maximum accumulation of NH2OH and NO2- -N were 9.42 mg/L and 0.02 mg/L
      respectively, it was speculated that NH2OH was transformed to N2O and N2 directly
      by strain qy37. In aerobic denitrifying system utilized sodium nitrite as
      nitrogen source, the concentration of NO2- -N reduced from 109.25 mg/L to 2.59
      mg/L by strain qy37 in 24 hours, and the maximum accumulation of NH2OH was 3.28
      mg/L. Compared with heterotrophic nitrifying system, aerobic denitrifying system
      had a higher bacterial growth whereas the lower removal rate of TN and COD, as
      well as the accumulation of NH2OH. NO3- -N was also detected in aerobic
      denitrifying system. It is considered that the upgrowth of bacterium and
      utilization of energy in aerobic denitrifying system were more efficient than
      that in heterotrophic nitrifying system. In heterotrophic nitrification-aerobic
      denitrification system, the removal rate of NH4+ -N improved 37.31% in 16 hours
      than that in heterotrophic nitrifying system, the accumulation of NH2OH was less
      but N2O was higher than that in both heterotrophic nitrifying system and aerobic
      denitrifying system.

PMID- 21090300
TI  - [Preliminary research on a new method of NO3- -N wastewater treatment based on
      electrochemistry].
AB  - A new method based on electrochemistry was presented to treat NO3- -N wastewater
      by analyzing theories of Pd-Me bimetal catalytic reduction of NO3- -N and NH4+ -N
      break point chlorination process. Presented method mainly includes following
      characteristics. Firstly, NO3- -N can be catalytically reduced in electric field
      while Ti substrate cathode was modified by common metallic elements which have
      empty electronic track. Secondly, NO3- -N reduction product can be controlled
      mainly is NH4+ -N by adjusting ratio of catalytic elements and electrolysis
      conditions. Finally, NH4+ -N is oxidized to harmless product N2-N by HOCl which
      produced from Cl- by anode oxidation process. Experiments were carried out to
      verified upwards theoretical assumptions. It's indicated that cathode modified by
      metal elements of Co and Cu can catalytic reduce NO3- -N in simulated wastewater
      effectively, as well as reduction product mainly was NH4+ -N while the molar
      ratio of Co and Cu in cathode precursor solution was 1:1. If Cl- was added to
      electrolysis system, NH4+ -N produced from NO3- -N reduction could be oxidized to
      N2-N by the anode action. Under the conditions of plate distance of 6mm, electric
      current of 400 mA and electrolysis time of 2.5 h, the concentration of NO3- -N,
      NO2- -N, NH4+ -N, and TN of simulated wastewater which initially contain 100 mg/L
      NO3- -N and 1000 mg/L Cl- decreased to 2.9 mg/L, 0.5 mg/L, 1.7 mg/L and 6.0 mg/L
      respectively.

PMID- 21090301
TI  - [Performance and process kinetics of pilot-scale ANAMMOX bioreactor under
      different water temperatures].
AB  - Performance and process biokinetics of the upflow pilot-scale anaerobic ammonium
      oxidation (ANAMMOX) reactor were investigated at ambient temperature. The results
      of substrate testing showed that the pilot-scale ANAMMOX reactor operated stably
      when the influent nitrite concentration reached (380.4 +/- 18.3) mg x L(-1);
      while the nitrite inhibition occurred when its concentration arrived at (480.5 +/
      21.9) mg x L(-1). The results of shortening of hydraulic retention time (HRT)
      showed that the HRT could be shortened to 3.43 h, and the nitrogen removal rate
      was as high as 3.45 kg x (m3 x d)(-1). Temperature was found to affect the
      performance of the ANAMMOX reactor significantly during long-term operation. The
      modified Stover-Kincannon model was applied to model the non-inhibition
      performance of the pilot-scale reactor under different temperature ranges. Good
      fitting results were obtained. The process biokinetic parameters and effluent
      substrate concentration prediction equations as well as the substrate removal
      efficiency prediction equations obtained in different temperature ranges are
      helpful to the stable operation of the pilot-scale ANAMMOX bioreactor.

PMID- 21090302
TI  - [Denitrification and kinetic characteristics using biodegradable polymers as
      carbon source and biofilm carrier].
AB  - The PBS material that in the form of insoluble biodegradable polymers pellets was
      investigated as the solid carbon source and the biofilm carrier for nitrate
      removal from wastewater. The denitrification of nitrate removal and kinetic
      process were carried out in a packed-bed reactor in order to remove nitrate in
      recirculation aquaculture system. The experimental results indicated that the
      optimal influent loading rate was in the range of 0.107-1.098 kg/(m3 x d), when
      the water temperature was (29 +/- 1) degrees C and the influent nitrate
      concentration was in the range of 25-334 mg/L. The maximum nitrate volumetric
      removal rate of 0.577 kg/(m3 x d) was achieved at the influent loading rate of
      1.098 kg/(m3 x d). When the influent loading rate exceeded 1.098 kg/(m3 x d), the
      nitrate volumetric removal rate was declined. The kinetic experimental results
      show that the denitrification rate of PBS as the solid carbon source and the
      biofilm carrier corresponds to first-order kinetics. Based on the kinetics
      characteristics, constants n and K used in Eckenfelder model were deduced, which
      can be successfully applied for the prediction of effluent nitrate concentration.
      The two groups' predictive values and actual values were analyzed by using SPSS
      16.0 software for Paired-Samples t test analysis. The Paired-Samples t test
      analysis indicates that the corresponding p > 0.05 values are 0.553 and 0.632,
      which proved that no significant differences exist between the predictive values
      and actual values of the model.

PMID- 21090303
TI  - [Effect of the influent COD and C/N ratio on phosphorus removal of UCT system].
AB  - UCT is deeply influenced by COD and C/N ratios. To check this infection, the UCT
      system was designed to run at variety of influent COD and C/N ratios. The results
      show that: when the influent C/N ratio is lower than 15, the high influent
      concentration of COD increases the proliferation of heterotrophic bacteria and
      decreases the phenomenon release rate. When the influent C/N ratio is higher than
      20, the low influent concentration of TN decreases the proliferation of
      heterotrophic bacteria, the phenomenon release rate rise with the increase of
      COD. When the influent concentration of COD is lower than 350 mg/L, the
      phenomenon of denitrifying phosphorus-uptake is very remarkable. The phenomenon
      release is remarkable when the influent concentration of COD is higher than 350
      mg/L. When the influent concentration of COD is lower than 350 mg/L, the
      promotion of C/N ratio which in the range of 10-20 is obvious, and the promotion
      decreases along with the increase of C/N ratio. The removal efficiency of total
      phosphorus achieve higher than 80% steadily when the influent concentration of
      COD in the range of 250-450 mg/L even in different influent C/N ratio.

PMID- 21090304
TI  - [Development of a novel hybrid UAFB-anoxic-aerobic MBR for energy production and
      nutrients removal from domestic wastewater].
AB  - The combined treatment process making up of up-flow anaerobic sludge fixed bed
      (UAFB), anoxic tank and aerobic membrane bioreactor (MBR) was used to treat
      domestic wastewater. And the ability of reclaiming methane and reusing wastewater
      was investigated. The efficiency of the combined treatment process treating
      wastewater at optimized parameters was studied in this paper. The combined
      treatment process treating domestic wastewater run at optimized parameters (20
      degrees C, HRT were 3 h, 3 h, 3.5 h) indicated that, the anaerobic gas production
      was 1.55 L/d, the COD and NH4+ -N removal efficiency were 93.28% and 90.60%
      respectively, UAFB effluent including 54.74 mg/L of total VFAs, corresponding NO3
      -N accumulating rate was 45.19% and TN removal efficiency was 45.51%. At the
      same time, it was found that sludge concentration of anoxic tank and aerobic MBR
      could be maintained at a low level, which is so rich in significance for sludge
      reduction and delaying membrane fouling.

PMID- 21090305
TI  - [Rice straw and sewage sludge as carbon sources for sulfate-reducing bacteria
      treating acid mine drainage].
AB  - The performance of three organic carbon sources was assessed in terms of sulfate
      reduction and main metal removal, by using sewage sludge as the source of sulfate
      reducing bacteria (SRB) and adding rice straw and ethanol with equal quantity.
      Results indicated that sewage sludge which contained certain amount of alkaline
      material could neutralize acidity of acid mine drainage(AMD) on the first day of
      experiment, elevating pH value from the initial 2.5 to around 5.4-6.3 and
      achieving suitable pH condition for SRB growth. Sewage sludge contained fewer
      biodegradable organic substance, reactive mixture with single sewage sludge
      showed the lowest sulfate reduction (65.9%). When the single sewage sludge was
      supplemented with rice straw, SRB reducing sulfate was enhanced (79.2%), because
      the degradation rate of rice straw was accelerated by the specific bacteria in
      sewage sludge, providing relatively abundant carbon source for SRB. Control
      experiment with ethanol was most effective in promoting sulfate reduction
      (97.9%). Metal removal efficiency in all three reactors was as high as 99% for
      copper, early copper removal was mainly attributed to the adsorption capacity of
      sewage sludge prior to SRB acclimation. It is feasible for using rice straw and
      sewage sludge as carbon sources for SRB treating acid mine drainage at a low
      cost, this may have significant implication for in situ bioremediation of mine
      environment.

PMID- 21090306
TI  - [Study on gfp labeling of a 2,4-D degrading strain and its detection in a
      wastewater biotreatment system].
AB  - A 2,4-dichlorophenoxyacetic acid (2,4-D) degrading special bacteria Achromobacter
      sp. was chromosomally labeled with a green fluorescent protein gene (gfp) using a
      mini-Tn7 transposon delivery system. The growth status, fluorescence expression
      and degradation ability of the strain before and after labeling were compared.
      Methods to quantify the strain in different biotreatment systems (activated
      sludge or granular sludge system) after inoculation were also investigated.
      Results showed that the labeled Achromobacter sp. and its control strain
      demonstrated a similar growth pattern and 2,4-D degradation ability: both of them
      could completely remove 2, 4-D of about 100 mg/L within 103-112 h. The labeled
      strain could express fluorescence stably during the course of growth and
      degradation with fluorescence intensity/D600 stabilized at about 4500. For an
      activated sludge system bioaugmented with this labeled strain, its abundance
      could determined through direct measuring fluorescence emitted by the sludge
      mixture, for it was linearly associated to the percentage of the strain in the
      range of 0-75% (R2 = 0.9952). For a granular sludge system bioaugmented with this
      strain, fluorescence of the sludge mixture could be measured after homogenous
      pretreatment, and the percentage of the strain in the range of 0-42% was also
      linearly related to the fluorescence intensity emitted by the sludge mixture (R2
      = 0.9801). Overall, this gfp labeling method based on Tn7 delivery system can be
      used to monitor specific bacteria in a biotreatment system.

PMID- 21090308
TI  - [Adsorption behavior and influence factors of p-nitroaniline on high surface area
      activated carbons prepared from plant stems].
AB  - Low-cost and high surface area microporous activated carbons were prepared from
      Spartina alternilora and cotton stalk with KOH activation under the conditions of
      impregnation ratio of 3.0, activation temperature at 800 degrees C and activation
      time of 1.5 h. The adsorption behavior of p-nitroaniline on the activated carbons
      was investigated by batch sorption experiments. The influences of solution pH
      value, adsorbent dose and temperature were investigated. The adsorption isotherm
      and thermodynamic characteristics were also discussed. The Spartina alterniflora
      activated carbon (SA-AC) has a high surface area of 2825 m2 x g(-1) and a
      micropore volume of 1.192 cm3 x g(-1). The BET surface area and micropore volume
      of the cotton stalk activated carbon (CS-AC) are 2135 m2 x g(-1) and 1.011 cm3 x
      g(-1), respectively. The sorption experiments show that both the activated
      carbons have high sorption capacity for p-nitroaniline. The Langmuir maximum
      sorption amount was found to be 719 mg x g(-1) for SA-AC and 716 mg x g(-1) for
      CS-AC, respectively. The sorption was found to depend on solution pH, adsorbent
      dose, and temperature. The optimum pH for the removal of p-nitroaniline was found
      to be 7.0. The Freundlich model and Redlich-Peterson model can describe the
      experimental data effectively. The negative changes in free energy (delta G0) and
      enthalpy (delta H0) indicate that the sorption is a spontaneous and exothermic
      procedure. The negative values of the adsorption entropy delta S0 indicate that
      the mobility of p-nitroaniline on the carbon surface becomes more restricted as
      compared with that of those in solution.

PMID- 21090307
TI  - [Fractal characteristics of mature aerobic granular sludge cultivated by
      different carbon sources].
AB  - In order to characterize the dense and regular level of aerobic granular sludge
      (AGS) which was cultivated by different carbon sources, the SEM images of mature
      AGS were used in the study. The calculation process using Photoshop and Fips2 on
      fractal characteristics of these granules was built. The lowest box-counting
      dimension was bulking aerobic granular sludge cultivated by glucose (No. 1),
      which was 1.794 +/- 0.011; the box-counting dimension of AGS cultivated by
      peptone (No. 3) and domestic sewage (No. 5) were reached up to 1.866 +/- 0.018
      and 1.880 +/- 0.015. The boundary box-counting dimension of the AGS was also
      calculated and the average value was 1.14. The AGS cultivated by beer (No. 6) was
      more regular in shape and the boundary box-counting dimension was 1.115 +/-
      0.003. The AGS cultivated by landfill leachate (No. 7) was the most irregular in
      shape. This study indicates that fractal dimension provides an approach for
      quantification of dense and regular level of AGS, furthermore, it could be used
      to characterize the status of AGS, such as bulking.

PMID- 21090309
TI  - [Effects of pH and coexisting cations on ammonia adsorption from aqueous solution
      by strawberry stem powder].
AB  - Batch equilibrium experiments were carried out to study ammonia adsorptions from
      aqueous solution by strawberry (Fragaia ananassa Duchesne) stem powder. The
      effects of pH, coexisting cations, initial ammonia concentration and temperature
      were investigated as well. The results showed that the equilibrium data fitted
      well to the Langmuir model and Freundlich model, and the maximum adsorption
      capacities were 3.05, 4.24 and 4.79 mg x g(-1) at 15, 25 and 35 degrees C
      respectively. The increase of temperature was favorable to ammonia adsorption.
      The optimal pH of ammonia adsorption was in the range of 4-8. The NH4+ content
      decreased at higher pH and the negative charges decreased at lower pH, resulting
      in the decrease of ammonia adsorption at both higher and lower pH. The pH changes
      after adsorption buffered both effects. K+, Na+, Ca2+ and Mg2+ had no effect on
      ammonia adsorption by strawberry stem, but Zn2+ and Al3+ decreased the adsorption
      for their hydrolyzation. The ammonia adsorption by strawberry stem powder could
      be applied in a large pH range and could not be affected by usual metal cations
      in wastewater, therefore the strawberry stem powder not only could be a suitable
      ammonia adsorbent, but also had advantages comparing with most mineral materials.

PMID- 21090310
TI  - [Phosphate adsorption characteristics on the desert particulates of inflow Yellow
      River].
AB  - Adsorption behaviors of phosphate on the desert particulates of inflow Yellow
      River were investigated in natural water (river water and sea water) and the
      experimental data was fitted by both the improved Langmuir and Freundlich
      isotherm adsorption models. The results show that (1) With more clear physical
      meaning and more reasonable fitting parameters, the improved Langmuir isotherm
      adsorption model is much better for describing phosphate adsorption on the desert
      particulates than the improved Freundlich isotherm adsorption model; (2) The
      maximum phosphorus (P) adsorption capacity Qmac is in the range of 41.322-357.143
      mg x kg(-1), which is the biggest in Y2 (Juyanhai Lake particulates). There is
      remarkable positive correlation between Qmax and organic matter of the
      particulates (Y1-Y5); (3) Except for Y1 (Badain Jaran Desert particulates), the
      EPC0 (zero equilibrium P concentration) of the particulates are higher than the
      concentration of P in corresponding water. The EPC0 of P adsorption on Y1 in
      Yellow River is lower than P concentration in corresponding water (0.010 mg x L(
      1) < 0.053 mg x L(-1)), while the EPC0 of P adsorption on Y1 in Bohai Sea water
      is higher than the P concentration in their corresponding water (0.109 mg x L(-1)
      > 0.074 mg x L(-1)), which shows that Y1 adsorbs P from the water of the Yellow
      River, then it releases its NAP (native adsorbed exchangeable phosphorus) into
      Bohai Seawater. However, in the process of the P exchange between other desert
      particulates and their corresponding water, only desorption phenomenon were
      observed, which means all other desert particulates release P to their
      corresponding water; (4) The adsorption isotherms of phosphate on the desert
      particulates of inflow Yellow River are cross-axis-type with over 0.00, a new
      cross-axis-type adsorption-desorption model, which provide a better explanation
      for adsorption characteristics of P and for the dual role of natural
      particulates.

PMID- 21090311
TI  - [Evaluation on biodegradability of hydrocarbon biomarkers in two crude oils under
      laboratory conditions].
AB  - Biodegradabilities of several hydrocarbon biomarker groups, including isoprene,
      hopanes and steranes in a medium-crude oil BZ34-1 and a heavy-crude oil SZ36-1
      from offshore, were determined under laboratory conditions. The results of GC-MS
      analysis showed that isoprene biomarkers such as pristane and phytane in both
      crude oils degraded obviously in 60-day experiment period. The degradation ratios
      of pristane and phytane in the medium-crude oil BZ34-1 reached 20.2% and 15.0%,
      respectively; while those in the heavy-crude oil SZ36-1 reached 95.6% and 75.4%,
      respectively. Pristane and phytane in the heavy-crude oil SZ36-1 were degraded in
      the early period of biodegradation, but these two biomarkers in the medium-crude
      oil BZ34-1 were degraded in middle and late biodegradation phases. However,
      hopanes and steranes in the both oils were not biodegraded obviously during the
      whole period. These results indicated that pristane and phytane could be used to
      evaluate bioremediation efficiency in the early biodegradation phase for light or
      medium oils, while hopanes and steranes could be used to evaluate bioremediation
      efficiency within the whole given experiment process.

PMID- 21090312
TI  - [Analysis of short-chain chlorinated paraffins in sediment samples from the mouth
      of the Daliao River by HRGC/ECNI-LRMS].
AB  - An analytical method for quantifying short-chain chlorinated paraffins (SCCPs) by
      high-resolution gas chromatography/electron capture negative ion low-resolution
      mass spectrometry (HRGC/ECNI-LRMS) was presented. The cleanup procedure with an
      acid silica gel column and activated neutral alumina column was optimized to
      remove the interferences. As illustration of the application of the method to
      environmental samples, it is found that lower chlorinated C10 and C11 compounds
      were the main SCCPs compounds in six sediment samples from the mouth of the
      Daliao River. The concentrations of SCCPs in sediments were determined to be in
      the range of 64.9-407.0 ng/g and showed a decreasing tendency from the shore to
      the remote location.

PMID- 21090313
TI  - [Effects of sediment resuspension on bacterioplankton community composition].
AB  - To determine the response of bacterioplankton community to sediment resuspension
      we set up two different intensities of the sediment resuspension in experimental
      microcosms. We employed the terminal restriction fragment length polymorphism (T
      RFLP), denaturing gradient gel electrophoresis (DGGE) methods to characterize the
      bacterial community structure. The result demonstrated that the species richness
      of the bacterioplankton in the treatment with sediment resuspension was higher
      than that in the controls without sediment resuspension. The bacterioplankton
      species richness and community diversity in the treatment with weak sediment
      resuspension (WR) was higher than that with strong sediment resuspension (SR).
      The relationship between bacterioplankton and environmental factors were
      investigated using canonical correspondence analysis (CCA) and redundancy
      analysis (RDA). The CCA and RDA results showed that there was a high degree of
      correlation between bacterioplankton community composition with Cladocera and
      particulate phosphorus (PP). It indicates that the sediment resuspension of
      shallow lakes has a significant effect on the species richness and diversity of
      bacterioplankton. We speculate the main reason is the dynamics of zooplankton
      community structure and the function of nutrient concentration influenced by the
      sediment resuspension.

PMID- 21090314
TI  - [Factors affecting the DAPI fluorescence direct count in the tidal river
      sediment].
AB  - The factors affecting the DAPI (4', 6-diamidino-2-phenylidole) fluorescence
      direct count in the tidal river sediment were examined. Sediment samples were
      collected from the Guangzhou section of the Pearl River. Besides sediment texture
      and organic matter, an improved staining procedure and the involved parameters
      were analyzed. Results showed that the procedure with the sediment with 2000 fold
      dilution and ultrasonic water bath for 10 min, and with a final DAPI
      concentration of 10 microg x mL(-1) and staining time for more than 30 min
      produced the optimum results of DAPI direct count in the sediment. The total
      bacterial number was correlated to the proportion of the non-nucleoid-containing
      cells to the total bacterial number (r = 0.587, p = 0.004). The organic matter
      content also correlated to the ration. The clay content had a strong correlation
      with the organic matter, through which the clay content also affected the ratio.
      A multiple regression analysis between the ration versus the organic matter, the
      total bacterial number, and the clay content showed that the regression equation
      fit the measure values satisfactorily (r = 0.694). These results indicated that
      the above factors needed to be considered in the applications of the DAPI
      fluorescence direct counting method to the tidal river sediment.

PMID- 21090315
TI  - [Cellulose degradation and ethanol production of different Clostridium strain].
AB  - Cellulose degradation and ethanol production of two types of cellulosic materials
      with different concentration were evaluated in batch system of mono-cultures of
      cellulolytic ethanol producing strains (Clostridium thermocellum strain LQRI and
      Clostridium thermocellum strain VPI), and co-cultures of LQRI or VPI in
      combination with one of the non-cellulolytic ethanol producing strains
      (Thermoanaerobacter ethanolicus strains X514 or Thermoanaerobacter ethanolicus
      39E). Results demonstrated that higher cellulose degradation abilities about 1.2
      times were detected in LQRI mono-culture than in VPI mono-culture, while no
      significant difference of ethanol yields was found between the two mono-cultures.
      Abilities of cellulose degradation and ethanol production decreased significantly
      with the increasing of substrate cellulose concentration (1%, 2%, 5%). In the co
      culture system, cellulose degradation abilities of LQRI were also significantly
      higher than VPI, the former is 1.28-1.58 times of the latter. Cellulose
      degradation rate of LQRI + Thermoanaerobacter and VPI + Thermoanaerobacter
      decreased gradually with the increasing of substrate cellulose concentration,
      while the absolute value of cellulose degradation was also affected by the
      partner Thermoanaerobacter strain. Additionally, the ethanol yields in the co
      cultures of LQRI + Thermoanaerobacter were significantly higher than that in the
      co-cultures of VPI + Thermoanaerobacter with same Thermoanaerobaeter partner, the
      former is 1.27-1.77 times of the latter. However, ethanol yields in the co
      cultures have not significantly declined with the increasing of substrate
      cellulose concentration.

PMID- 21090316
TI  - [Biocathode denitrification in a two-columnar microbial fuel cell].
AB  - The biocathode of the two-columnar microbial fuel cell was used to denitrify.
      Factors influencing denitrification performance and power production were
      studied. When the external resistance decreased from 50 omega to 5 omega, the
      nitrate removal rate increased from 0.26 mg/(L x h) to 0.76 mg/(L x h). The
      nitrite accumulated to 55 mg/L with the external resistance decreasing to 5
      omega. The nitrate degradation followed the zero order reaction model when the
      initial nitrate concentration was 20-120 mg/L. The power generation was not
      affected by the nitrate concentration distinctly. The nitrite concentration
      increased with the initial nitrate concentration. The nitrite removal could be
      enhanced by adding organic matter, without significant influence on the power
      generation.

PMID- 21090317
TI  - [Ammonia volatilization of slow release compound fertilizer in different soils
      water conditions].
AB  - By using venting method incubation experiment, we studied the ammonia
      volatilization and kinetics characteristics of uncoated slowed release compound
      fertilizer (SRF) under different soil water conditions and the growth and
      nitrogen utilization efficiency of rice in pot experiment. Results indicated that
      the ammonia volatilization of SRF under waterflooding reached the peak ahead of 3
      4 days compared to the moist treatment. The peak and accumulation of ammonia
      volatilization in the waterflooding treatments were higher than those under the
      moist condition. SRF could significantly reduce total ammonia volatilization
      compared to the common compound fertilizer (CCF), reduced by 50.6% and 22.8% in
      the moist treatment and reduced by 24.2% and 10.4% in the waterflooding
      treatment,but the loss of ammonia volatilization of SRF was higher significantly
      than that of the coated fertilizer (CRF). Ammonia volatilization increased with
      the increasing of fertilizer application. The dynamics of ammonia volatilization
      of SRF could be quantitatively described with three equations: the first order
      kinetics equation, Elovich equation and parabola equation. Compared to moist
      condition, the biomass of rice plant in SRF, CCF and SRF treatments increased by
      67.86%, 78.25% and 48.75%, and nitrogen utilization efficiency increased by
      57.73%, 80.70% and 12.06% under waterflooding condition, respectively. Comparing
      with CCF, nitrogen utilization efficiency in SRF treatment improved by 59.10% and
      10.40% under two soil moisture conditions. SRF could reduce ammonia
      volatilization and improve biomass and nitrogen utilization efficiency.

PMID- 21090318
TI  - [Effects of fungi on co-metabolic degradation of benzo [a] pyrene in droughty red
      soil].
AB  - Simulated bioslurry remediation of PAHs contaminated soil was carried out.
      Penicillium, Aspergillus niger and white-rot fungus etc. three strains of fungi
      isolated from petroleum-contaminated soils were inoculated into droughty red
      soils differently in application rates of phenanthrene and phthalic acid, to
      investigate their effects of co-metabolic degradation of B[a]P. Results show that
      in natural soils, some native microorganisms were able to degrade B[a] P and with
      addition of low molecular weight PAHs-phenanthrene increased degradation rate of
      B[a] P in the soil. The effect was greater when the application rate of
      phenanthrene was 100 mg x kg(-1) than 200 mg x kg(-1). But the addition of
      phthalic acid did not show much effect. In sterilized soils, degradation of B[a]P
      in soils was hardly observed, and application of co-metabolism has no significant
      effect. However, inoculation of Penicillium stimulated degradation of B[a]P in
      all three treatments, i.e., phenanthrene at 100 mg x kg(-1), phenanthrene at 200
      mg x kg(-1) and phthalic acid, but the effect of phenanthrene treatment was
      better than that of phthalic acid treatment. Inoculation of Aspergillus niger
      also showed similar effect, however, was inhibited by the presence of
      phenanthrene and phthalic acid in the soil. The degradation ability of white-rot
      fungus to B[a]P was very poor, but both kinds of phenanthrene concentration and
      phthalic acid treatments all could promote white-rot fungus to degrade B[a]P in
      soils, and the effect of phenanthrene was better than that of phthalic acid.

PMID- 21090319
TI  - [Contents and movement of phosphorus in soil of long term effluent irrigated land
      forest].
AB  - Treated sewage effluent from Rotorua City, New Zealand, has been spray-irrigated
      into Whakarewarewa Forest to minimize effluent-derived nitrogen (N) and
      phosphorus (P) entering Lake Rotorua. To assess the capacity of the ecosystem to
      assimilate the effluent derived nutrients, a long term field trial was
      established within the Rotorua land treatment system. The objective of this study
      was to determine the accumulation, redistribution and movement of P in the
      volcanic soil after 11 year effluent irrigation. The soil samples were analyzed.
      Soil pH, total phosphorus (TP), Olsen P, Mehlich-3 P(M3P), M3Ca and M3Mg had
      increased significantly (p < 0.05) in the top soil (0-10 cm) in all effluent
      treated plots compared with the control plots. Some significant increase had
      extended deeper soil layer (20-40cm) or much deeper soil layer. Most effluent
      derived P had accumulated in top 40cm. Concentrations of soil Olsen P and M3P in
      the medium and high effluent treatments were over environmental threshold levels
      (Olsen P, 60 mg x kg(-1); M3P, 150 mg x kg(-1)) in the top 20 cm. The values of
      soil saturation ratio (M3PSR) show that it was nearly saturated of soil P
      sorption in top soil. It was suggested that there was a potential environment
      crisis for soil P to move downward with drainage water. Regular soil sampling and
      Olsen P measurement using 60 mg x kg(-1) as an environment threshold could
      provide a solution for monitoring the movement of P down the soil profile.
      Phosphorus saturation ratio index (M3PSR) calculated as the molar ratio of M3P to
      (M3Al + M3Fe) appeared to be inadequate as an indicator for downward movement of
      soil P in such land treatment system. A new Phosphorus saturation ratio index for
      this system will be one of future study work.

PMID- 21090320
TI  - [Impacts on N and P conservation during swine manure composting with different
      modified metal-salts addition].
AB  - Batch experiments were carried out by using mixed-level uniform design method U6
      (692) x 3) to investigate the effect of the addition of different metal-salts at
      20%, 40% and 60% of NT, respectively, including modified red-mud (MR) at pH 5.0
      +/- 0.2 and 7.0 +/- 0.2, respectively, modified forsterite (MF) at pH 7.0 +/-
      0.2, and MgSO4 on nitrogen and phosphorus conservation during swine manure
      composting. The results showed that the optimum effect of N saved occurred at No.
      5 experiment (20%, MF, day 17) and No. 3 experiment (40%, MgSO4, day 10).
      Meanwhile, the P conservation of experiments with metal salts addition was better
      than that of the control, and the No. 6 experiment (20%, MR with pH =5, day 21)
      was the highest on TP conservation, with the lowest ratio of PO4(3-) -P/TP.

PMID- 21090321
TI  - [Thermal treatment behavior of PCDD/Fs on the fly ash from medical waste
      incineration].
AB  - PCDD/Fs formation distribution in gas phase and solid phase of medical waste
      incineration fly ash under both the flowing nitrogen and static air condition
      were studied within temperature range of 200-450 degrees C. Under the flowing
      nitrogen, PCDD/Fs in solid phase increased with temperature increase, which
      reached the maximum concentration at 350 degrees C, both the TEQ and total
      concentration increased 46.0% and 26.0% respectively of original concentration,
      then, which decreased with temperature's rising, reaching the lowest level at 450
      degrees C, of which 86.8% and 80.5% respectively in turn removed. Under the
      static air, the maximum concentration in solid phase occurred at 250 degrees C,
      both the TEQ and total concentration increased 20.7% and 28.7% respectively of
      original concentration, then, which decreased with temperature increase, reaching
      the lowest level at 450 degrees C, of which 99.5% and 99.5% respectively in turn
      removed. There were small generation of PCDD/Fs in gas phase, which took only
      0.11%-2.16% of the total quantity of PCDD/Fs in both gas phase and solid phase.
      The optimal conditions for thermal treatment in this study were under the static
      air at temperature of 450 degrees C in duration of 1 h. The mechanism of
      destruction played the main role in the thermal treatment, while dechlorination
      and desorption acted as minor role in this study.

PMID- 21090322
TI  - [Novel process utilizing alkalis assisted hydrothermal process to stabilize heavy
      metals both from municipal solid waste or medical waste incinerator fly ash and
      waste water].
AB  - An alkalis assisted hydrothermal process was induced to stabilize heavy metals
      both from municipal solid waste or medical waste incinerator fly ash and waste
      water. The results showed that alkalis assisted hydrothermal process removed the
      heavy metals effectively from the waste water, and reduced leachability of fly
      ash after process. The heavy metal leachabilities of fly ash studied in this
      paper were Mn 17,300 microg/L,Ni 1650 microg/L, Cu 2560 microg/L, Zn 189,000
      microg/L, Cd 1970 microg/L, Pb 1560 microg/L for medical waste incinerator fly
      ash; Mn 17.2 microg/L, Ni 8.32 microg/L, Cu 235.2 microg/L, Zn 668.3 microg/L, Cd
      2.81 microg/L, Pb 7200 microg/L for municipal solid waste incinerator fly ash.
      After hydrothermal process with experimental condition [Na2CO3 dosage (5 g
      Na2CO3/50 g fly ash), reaction time = 10 h, L/S ratio = 10/1], the heavy metal
      removal efficiencies of medical waste incinerator fly ash were 86.2%-97.3%, and
      94.7%-99.6% for municipal solid waste incinerator fly ash. The leachabilities of
      both two kinds of fly ash were lower than that of the Chinese national limit. The
      mechanism of heavy metal stabilization can be concluded to the chemisorption and
      physically encapsulation effects of aluminosilicates during its formation,
      crystallization and aging process, the high pH value has some contribution to the
      heavy metal removal and stabilization.

PMID- 21090323
TI  - [Difference of root anatomy characteristics and its effect on DEHP accumulation
      in two genotypes of Brassica parachinensis].
AB  - Two genotypes of Brassica parachinensis, DEHP high-accumulation of Youqing-60 and
      low-accumulation of Teqing-60, were grown in hydroponic systems contaminated with
      DEHP (20 and 50 mg x L(-1)). Anatomy of roots was measured, and their effects on
      uptake of DEHP in roots and shoots were discussed. The results showed that roots
      anatomy of two genotypes of Brassica parachinensis and their responds to DEHP
      pollution were significantly different. DEHP contents in roots and shoots of
      Youqing-60 were mainly affected by the thickness of cambium in taproot and the
      diameter of vascular bundle, the coefficients on DEHP of roots and shoots were
      0.900 and 0.809, respectively. DEHP contents of Teqing-60 were mainly affected by
      the thickness of cambium in taproot and cortex in fibre root in roots, which the
      coefficient was 0.757, and were mainly affected by the thickness of cambium in
      taproot in shoots, which the coefficient was 0.856. The wood ray cells in roots
      of Youqing-60 were rectangular shape and arranged orderly. The thickness of cork
      layer in taproot and cortex in fibre root of Youqing-60 were lower and the
      quantity of trachea and diameter of vascular bundle and trachea in fibre root of
      Yonqing-60 were higher than that of Teqing-60, which indicated that DEHP in soil
      solution and adsorbed on root were easier penetrated into xylem and transported
      in Youqing-60 than in Teqing-60.

PMID- 21090324
TI  - [Effects of moxibustion on the expression of IL-1beta, IL-2, IL-6 mRNA and
      protein in the cerebral cortex in tumor-bearing mice].
AB  - OBJECTIVE: To investigate the effect of moxibustion on the expression of IL
      1beta, IL-2 and IL-6 proteins and mRNA in the cerebral cortex in tumor-bearing
      mice so as to study its mechanism underlying immunomodulation. METHODS: Forty
      Balb/c mice were randomly divided into control, tumor-bearing, non-acupoint
      moxibustion (N-AM) and acupoint-moxibustion (AM) groups (n = 10/group).
      Moxibustion was applied to "Dazhui" (GV 14), once every other day for 6 times.
      The expression of IL-1beta mRNA, IL-2 mRNA and IL-6 mRNA was detected by in situ
      hybridization, and the immunoactivity of IL-1beta, IL-6 and IL-2 determined by
      immunohistochemistry. RESULTS: Compared to the control group, the expression
      levels of IL-1beta mRNA and IL-2 mRNA, IL-1beta and IL-2 in the cerebral cortex
      of the tumor-bearing group were down-regulated significantly (P < 0.05, P <
      0.01), while those of IL-6 mRNA and IL-6 up-regulated significantly (P < 0.05).
      Compared to the tumor-bearing group, the expression of IL-1beta mRNA and IL-2
      mRNA, IL-1beta and IL-2 in the cerebral cortex in AM group were increased
      considerably (P < 0.05, P < 0.01); while cortical IL-6 immunoactivity in N-AM
      group was decreased significantly (P < 0.05), and IL-6 mRNA had no significant
      change in N-AM group (P > 0.05). Comparison between AM and N-AM groups showed
      that the expression levels of cortical IL-1beta mRNA and IL-2 mRNA, and IL-1beta
      and IL-2 proteins of the former group were obviously higher than those of the
      later group (P < 0.05, P < 0.01); while the immunoactivity of cortical IL-6 of AM
      group was significantly lower than that of N-AM group (P < 0.05). No significant
      difference between AM and N-AM groups in the expression of IL-6 mRNA (P > 0.05).
      CONCLUSION: Moxibustion treatment can up-regulate the expression of cortical IL
      1beta mRNA, IL-2 mRNA, IL-1beta and IL-2 proteins, and down-regulate the
      expression of IL-6 mRNA and IL-6 in tumor-bearing mice, which may contribute to
      its effect in improving the immunosuppressing state under tumor conditions.

PMID- 21090325
TI  - [Effects of moxibustion on the expression of cell cycle protein P 16 and
      retinoblastoma and c-fos in the cerebral cortex of senile mice].
AB  - OBJECTIVE: To observe the influence of moxibustion on the cyclin and cellular
      proliferin of the cerebral cortex in senile mice so as to explore its underlying
      mechanism in delaying aging. METHODS: Sixty male mice were randomly and equally
      divided into control, model, moxibustion of "Zusanli" (ST 36) and "Xuanzhong" (GB
      39, M-ST 36-GB 39), moxibustion of "Baihui" (GV 20) and "Guanyuan" (CV 4,M-GV 20
      COV 4) ,and medication groups. The aging model was established by subcutaneous
      injection of D-galactose for 42 days. Moxibustion was applied to ST 36, GB 39, GV
      20 and CV 4 separately for 3 moxa-cones, once every other day for one month. The
      expression of cell cycle protein P 16 and retinoblastoma (pRb), and c-fos protein
      in the cerebral cortex tissue of the senile mice were detected by
      immunohistochemistry. RESULTS: Compared with control group, the number of P16
      immunoreaction (IR) positive neurons in the cerebral cortex increased
      significantly in the model group (P < 0.01), and those of cortical pRb and c-fos
      IR-positive neurons decreased considerably in model group (P < 0.01). In
      comparison with the model group, the number of cortical P 16 IR-positive neurons
      reduced significantly in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P <
      0.01), and those of cortical pRb and c-fos IR-positive neurons increased
      remarkably in M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P < 0.01, P <
      0.05). No significant differences were found in the aforementioned 3 indexes
      among M-ST 36-GB 39, M-GV 20-CV 4 and medication groups (P > 0.05). CONCLUSION:
      Moxibustion of ST 36-GB 39 and GV 20-CV 4 can down-regulate the P 16
      expression,and up-regulate pRb and c-fos protein expression in the cerebral
      cortex of senile mice, which possibly contributes to its effect in delaying
      aging.

PMID- 21090326
TI  - [Effects of acupoint-injection of Lentinan on the immunologic funtion in rabbits
      with spleen-qi deficiency].
AB  - To observe the effect of Spleen-Meridian-acupoint injection of Lentinan on the
      immunologic function in spleen-deficiency rabbits. METHODS: A total of 54
      Newzealand rabbits were randomly divided into normal (n = 10), model (n = 8),
      intramuscular injection (n = 10), Sanyinjiao (SP6, n = 10), Diji (SP8, n = 8) and
      Xuehai (SP 12, n = 8) groups. Spleen-qi deficiency model was established by
      intragastric administration of 100% crude Radix et Rhizoma Rhei decoction (15
      mL/kg/day x 10 d), and then Lentinan (LNT, 0.025 mg/kg/2 day x 5) was injected
      into the aforementioned acupoints of the Spleen Meridian. The erythrocyte
      immunologic function (RBC-C3 bR, RBC-IC), hemolysin (lgM) and changes of physical
      signs of the rabbits were observed. RESULTS: In comparison with the control
      group, the rabbits' body weight, rectal temperature, RBC-C3 bR% and serum IgM
      level were decreased significantly in model group (P < 0.05); while in comparison
      with the model group, the body weight in SP 8 group,retal temperature in SP 9 and
      SP 8 groups, RBC-C3 bR% in SP 9 and SP 12 groups, and serum IgM levels in SP 9,
      SP 8 and SP 12 groups increased considerably (P < 0.05, P < 0.01). Comparison
      among the 4 treatment groups showed that the effect of SP 12 was superior to that
      of intramuscular injection group in upregulaing RBC-C3 bR%, and the effects of SP
      9, SP 8 and SP 12 groups were significantly superior to those of intramuscular
      injection group in upregulating serum IgM level (P < 0.05). CONCLUSION: The
      Spleen-Meridian-acupoint injection of LNT is superior to that of intramuscular
      injection of LNT in improving the spleen-qi deficiency rabbits' symptoms and
      immunologic function.

PMID- 21090327
TI  - [Effect of electroacupuncture of "Baihui" (GV 20)-"Yintang" (EX-HN 3) on the
      expression of glucocorticoid and glucocorticoid receptor mRNA of the chronic
      stress model rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of
      glucocorticoid (GC) mRNA and GC in the hippocampus, hypothalamus and pituitary in
      depression rats so as to study its mechanism underlying EA-resisting depression.
      METHODS: Seventy SD rats were randomized into normal control, model, Fluoxetine
      (Flu), constraint-stress, EA, RU 486 (an antagonist of GC) and EA+ RU 486 groups
      (n = 10/group). Chronic depression model was established by lonely raising and
      chronic unpredictable mild stress for 21 days. EA (2 Hz, 0.6 mA) was applied to
      "Baihui" (GV 20) and "Yintang" (EX-HN 3) for 20 min, once daily for 21 days.
      Subcutaneous injection of RU 486 (20 mg/kg) was given to the rats from the 14th
      day on and con- tinuously for 7 days in order to block the negative feedback
      reflex of hypothalamus-pituitary-adrenal (HPA) axis. Cortisol (CORT) content of
      the adrenal gland tissue was detected by radioimmunassay. The expression of GC
      receptor (GR) mRNA in the hippocampus, hypothalamus and pituitary tissues was
      determined by real-time quantitative reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: Compared with the normal control group, adrenal CORT
      content of model group was increased significantly (P < 0.05), and in comparison
      with model group, adrenal CORT level of EA group decreased evidently (P < 0.05).
      Comparison between the RU 486 and EA + RU 486 groups showed that the adrenal CORT
      content, and hippocampal GR mRNA expression level of the latter were remarkably
      lower than those of the former (P < 0.05). Compared with the normal control
      group, the expression level of GR mRNA of the hipppocampal and pituitary tissues
      in the model, constraint-stress, and RU 486 groups,and those of the hypothalamus
      in the constraint-stress and RU 486 groups were down-regulated significantly (P <
      0.05). In comparison with the constraint-stress group, hippocampal, hypothalamic
      and pituitary GR mRNA expression level in the EA group were upregulated
      considerably (P < 0.05). No significant differences were found among model, Flu,
      constraint-stress, RU 486 and EA + RU 486 groups in the ardenal CORT contents,
      and hippocampal, hypothalamic and pituitary GR mRNA expression levels (P > 0.05).
      CONCLUSION: EA can effectively down-regulate adrenal CORT content and hippocampal
      GR mRNA expression and normalize the function of HPA axis negative feed reflex in
      the depression rats, which may contribute to its effect in relieving depression.

PMID- 21090328
TI  - [Effect of needle-implantation at "Neiguan" (PC 6) on the expression of
      myocardial TGF-beta3 and its mRNA in the Chinese miniswine with myocardial
      ischemia injury].
AB  - OBJECTIVE: To observe the effect of needle-implantation (NI) at "Neiguan" (PC 6)
      on the expression of myocardial transforming growth factor-beta 3 Protein(TGF
      beta 3) and mRNA in Chinese miniswine with myocardial ischemia (MI) injury.
      METHODS: A total of 32 Chinese Guizhou miniswine were randomly and equally
      divided into Sham-operation group, model group, NI-PC 6 group and NI-Geshu (BL17,
      NI-BL17) group. MI injury model was established by occlusion of the descending
      anterior branch of the left coronary artery. Two acupuncture needles (veterinary
      use) were separately and subcutaneously implanted into "Neiguan" (PC 6) and
      "Geshu" (BL17) areas for 7 days. TGF-beta 3 protein and mRNA expressions were
      determined by Western blot and real-time PCR techniques, separately. RESULTS: In
      comparison with the sham-operation (sham) group, TGF-beta 3 protein and mRNA
      expressions in model group were upregulated significantly (P < 0.05). While
      compared with the model group, myocardial TGF-beta3 mRNA expression was
      upregulated considerably in NI-PC 6 group (P < 0.01), rather than in NI-BL17
      group (P > 0.05), and myocardial TGF-beta 3 expression in both NI-PC 6 and NI
      BL17 groups was upregulated obviously (P < 0.01). Comparison between NI-PC 6 and
      NI-BL17 groups showed that the expression levels of myocardial TGF-beta 3 protein
      and mRNA were significantly higher in NI-PC 6 group than in NI-BL17 group (P <
      0.05). CONCLUSION: Needle-implantation of "Neiguan" (PC 6) can upregulate
      myocardial TGF-beta 3 protein and mRNA expression in MI Chinese miniswine, which
      may contribute to its effect in improving the ischemic myocardial injury by way
      of enhancing the angiopoiesis.

PMID- 21090329
TI  - [Observation on the leptin level in the subcutaneous tissues of the high
      temperature reaction zone along the abdominal gallbladder Meridian in rabbits
      with cholecystitis].
AB  - OBJECTIVE: To observe the content of leptin in the abdominal subcutaneous tissues
      of the higher temperature zone along the Gallbladder (GB) Meridian in
      cholecystitis rabbits so as to explore the correlation between the temperature
      response and the leptin level. METHODS: Twenty-five rabbits were randomized into
      normal control group (n = 10) and cholecystitis model group (n = 15).
      Cholecystitis model was established by injection of Escherichia coli solution
      (0.1 mL) into the gallbladder via common bile duct after surgery. Three, 7 and 11
      days following modeling, the abdominal surface thermographic images along the GB
      Meridian were collected by the AGA-782-type infrared imaging system (AGA's
      capacity). And then the subcutaneous tissues of the high temperature reaction
      region and the contralateral corresponding tissues of different groups were
      collected for assaying the leptin contents in the supernatant by radioimmunoassay
      after processing (homogenization and centrifugation) and for observing the
      morphological structure under light microscopy after sectioning and staining
      (toluidine blue). RESULTS: Thermographic images showed that about 70% of the
      animals in the model group, various lengths of high temperature reaction (0.5-1.4
      degrees C) zones or bands in the abdominal region along the bilateral GB Meridian
      were seen, in comparison with the control group. The leptin levels in the
      ipsilateral (affected side) and contralateral (healthy side) tissues of the
      abdominal high temperature reaction zones along the GB Meridian were
      significantly higher in the model group than in the control group (P < 0.01),
      suggesting a close correlation between the leptin content change and the high
      temperature reaction. In addition, most fat cells were crowded to distribute
      closely along the blood vessels in the subcutaneous tissues of the higher
      temperature reaction zone in the model group, but those of the control group
      distribute more loosely along the blood vessels. CONCLUSION: The leptin content
      in the abdominal sub- cutaneous tissues of high temperature reaction zone along
      the GB Meridian is higher in cholecystitis rabbits, suggests a relevance of the
      endocrine function of fat cells to the high temperature reaction along the GB
      Meridian.

PMID- 21090330
TI  - [Effect of electroacupuncture on hypothalamic leptin and leptin receptor mRNA
      expression in rats with nonalcoholic fatty liver disease].
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) on leptin and leptin
      receptor(Ob-rb) mRNA expression in the hypothalamus of nonalcoholic fatty liver
      disease (NAFLD) rats, so as to reveal its underlying mechanism in the treatment
      of NAFLD inflammation. METHODS: Thirty-two male SD rats were randomly divided
      into control group (n = 10), model group (n = 11) and EA group (n = 11). NAFLD
      model was established by feeding the animals with high fat diet for 8 weeks. EA
      (10 Hz, 1.5 V, 30 min) was applied to unilateral "Fenglong" (ST 40) and "Zusanli"
      (ST 36), once daily for 4 weeks. After the treatment, all the rats were
      sacrificed for collecting the liver to make pathological observation after HE
      staining and for taking the hypothalamus tissue out to detect the leptin mRNA and
      leptin receptor (Ob-rb) mRNA expression by reverse transcription polymerase chain
      reaction (RT-PCR). Serum total cholesterol (TC) and triglyeride (TG) contents
      were detected by chromatometry. RESULTS: Compared with the control group, serum
      TC and TG levels increased significantly in the model group (P < 0.05). While
      compared with model group, both TC and TG levels in EA group were reduced
      considerably (P < 0.05). In comparison with control group, the expression of
      hypothalamic leptin mRNA and Ob-rb mRNA was down-regulated remarkably (P < 0.05),
      while 4 weeks after EA treatment, both leptin mRNA expression and Ob-rb mRNA
      expression were up-regulated obviously (P < 0.05). CONCLUSION: EA can lower serum
      TG and TC contents in NAFLD rats, which is closely related to its effects in up
      regulating the expression of hypothalamic leptin mRNA and Ob-rb mRNA.

PMID- 21090331
TI  - [Effect of transection or pretreatment of the infraorbital nerve with snake venom
      on the analgesia induced by electroacupuncture of "Sibai" (ST 2) acupoint in
      visceral pain rats].
AB  - OBJECTIVE: To observe the role of large-diameter fibers of infraorbital nerve
      (ION) in "Sibai" (ST 2)-electroacupuncture (EA) induced analgesia in visceral
      pain (VP) rats. METHODS: A total of 36 SD rats were randomized into control, VP,
      EA, ION transaction, snake venom (SV) and saline groups, with 6 rats in each
      group. EA(2 Hz/20 Hz) was applied to bilateral "Sibai" (ST 2) for 20 min. VP
      model was established by intraperitoneal injection of 0.6% acetic acid (10
      mL/kg). Bilateral ION were transacted or pretreated by regional application of
      snake venom to selectively destroy A fibers,respectively. Behavior reactions were
      assessed by counting abdominal muscular contractions. Meanwhile, c-fos expression
      in the nucleus of the solitary tract (NTS) and paratrigeminal nucleus (PTN) was
      displayed by immunohistochemistry. RESULTS: In comparison with control group, the
      numbers of abdominal muscular contraction,and c-fos immuno-reaction (IR) positive
      neurons in both NTS and PTN increased significantly in VP group (P < 0.001);
      while in comparison with VP group, the numbers of the abdominal contraction, and
      c-fos IR-positive neurons of both NTS and PTN in EA and SV and saline groups
      decreased considerably (P < 0.05, P < 0.01). No significant differences were
      found between ION transaction and VP groups in the abdominal contraction number,
      and c-fos IR-positive neurons in both NTS and PTN areas,and among EA and SV and
      saline groups in the numbers of abdominal contraction and c-fos IR-positive
      neurons of both NTS and PTN (P > 0.05). CONCLUSION: The large-diameter (A) fibers
      of ION are not the major afferent fibers affecting EA-ST 2 induced analgesia in
      visceral pain rats; and somatic sensory afferents from orofacial areas and
      visceral pain input converge in the NTS and PTN, which may be the basis of the EA
      analgesia in the present study.

PMID- 21090332
TI  - [Effects of electroacupuncture of "Weishu" (BL 21) and "Zhongwan" (CV 12) on
      serum large molecular metabolites in functional dyspepsia rats].
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) of Shu-acupoint
      "Weishu" (BL 21), Mu-acupoint "Zhongwan" (CV 12) and BL 21 + CV 12 on serum large
      molecular metabolites in functional dyspepsia (FD) rats. METHODS: A total of 50
      Wistar rats were randomly divided into control, model, BL 21, CV 12 and BL 21 +
      CV 12 groups (n = 10/group). FD model was established by clamping the rats' tails
      for 30 min, once every 3 h, 4 times daily for 7 days. EA was applied to BL 21,CV
      12, or BL 21 + CV 12, respectively for 20 min, once daily for 10 days. The rats'
      venous blood was collected for detecting large molecular metabolites by 1H
      nuclear magnetic resonance (NMR) spectrometer (Varian UnityInova, 600 MHz).
      Segmental integral calculus (0.04 ppm per segment) was performed from 6.0-0 ppm
      (longitudinal eddy-delay, LED) as defaulted 1H spectra values by using the VNMR
      software. Data was saved as text or excel files after normalization and then used
      for pattern recognition analyses. All the data were analyzed by principal
      component analysis (PCA) using the SIMCA-P 10.04 software (Umetrics AB, Umea,
      Sweden), and orthogonal signal correction and partial least squares discriminant
      analysis (OSC-PLS-DA). RESULTS: The rat serum proton-LED-1H NMR spectra revealed
      different metabolic spectra among control,model, BL 21, CV 12, and BL 21 + CV 12
      groups. PCA and OSC-PLS-DA showed that compared with the normal control group, FD
      rats in model group displayed serum N-acetylglucoprotein (NAc) content was
      reduced considerably, high density lipoprotein (HDL) level decreased to a certain
      degree, while very low density lipoprotein (VLDL)/LDL increased significantly. In
      comparison with model group, VLDL/LDL was decreased in BL 21, CV 12 and BL 21 +
      CV 12 groups, while NAc content increased. Compared with BL 21 and CV 12 groups
      respectively, HDL level in BL 21 + CV 12 increased to a certain degree.
      CONCLUSION: EA of BL 21, CV 12 and BL 21 + CV 12 groups can reverse or relieve FD
      induced increase of VLDL/LDL and decrease of serum NAc level in rats, which may
      contribute to its function in improving symptoms of FD patients.

PMID- 21090333
TI  - [Clinical observation on the therapeutic effect of drugs-paste separated
      moxibustion combined with electroacupunture for knee osteoarthritis patients of
      cold-damp type].
AB  - OBJECTIVE: To observe the curative effect of Chinese drugs-paste separated
      moxibustion combined with electroacupuncture (EA) for knee osteoarthritis (KOA).
      METHODS: A total of 124 cases of KOA patients were randomly and equally divided
      into moxibustion plus electroacupunture (M + EA) group and medication group by
      using a random table. Chinese drugs-paste separated moxibustion was applied to
      Shenque (CV 8) for 9 moxa-cones, combined with EA (4 Hz/20 Hz, 1-2 mA) of
      Liangqiu (ST 34), Heding (EX-LE 2), Neixiyan (EX-LE 4), etc. for 30 min, once
      daily, 5 sessions a week. Patients of medication group were treated by oral
      administration of Antine Capsule (diclofenac sodium, 50 mg, twice daily). After 4
      weeks of treatment, the therapeutic effect was evaluated. RESULTS: Compared with
      pre-treatment, the knee-joint pain scores and the index of severity of
      osteoarthritis of both M + EA and medication groups decreased significantly after
      termination of the treatment and 10 weeks after the treatment (P < 0.01), and
      those of M + EA group were markedly lower than those of medication group (P <
      0.05). After the treatment, of the two cases in medication and M + EA groups, 3
      (4.8%) and 8 (12.9%) were under control in their symptoms, 16 (25.8%) and 21
      (33.9%) had remarkable improvement, 31 (50.0%) and 27 (43.5%) were effective, 12
      (19.4%) and 6 (9.7%) failed in the treatment, with the effective rates being
      80.6% and 90.3% respectively. Ten weeks after the treatment, of the two 62 cases
      in medication and M + EA groups, 1 (1.6%) and 7 (11.3%) were under control, 10
      (16.1%) and 19 (30.6%) had marked improvement, 31 (50.0%) and 28 (45.2%) were
      effective, 20 (32.3%) and 8 (12.9%) failed in the treatment, with the effective
      rates being 67.7% and 87.1%, respectively. The curative effect of M + EA group
      was significantly superior to that of medication group (P < 0.05, P < 0.01).
      CONCLUSION: Chinese drugs-paste-separated moxibustion combined with EA is
      effective in the treatment of KOA of cold-damp type.

PMID- 21090334
TI  - [Effect of abdominal acupuncture therapy on the endocrine and metabolism in
      obesity-type polycystic ovarian syndrome patients].
AB  - OBJECTIVE: To observe the effect of abdominal acupuncture on the endocrine and
      metabolic level in obesity-type polycystic ovarian syndrome (PCOS) patients.
      METHODS: Eighty-six PCOS patients were randomly and equally divided into
      medication group and abdominal acupuncture group. Patients of medication group
      were treated with metformin (250 mg/time, t.i. d. in the 1st week, and 500
      mg/time, t.i.d. thereafter) for 6 months,and those of abdominal acupuncture group
      were treated by abdominal acupuncture [Zhongwan (CV 12), Liangmen (ST 21), etc.,
      once daily for 6 months]. Changes of the body height, body Mass index (BMI),
      waist-hip ratio (WHR), Ferriman-Galleey score (FGS), menstrual frequency (MF) and
      ovarian volume (OV) were determined. Serum luteotrophic hormone (LH), free
      testosterone (T), follicle-stimulating hormone (FSH) contents were detected with
      radioimmunoassay. Fasting blood glucose (FBG), fasting insulin (FIN), total
      cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C),
      high density lipoprotein cholesterol (HDL-C), Homa insulin resistance index (IRI)
      were detected with chromatometry respectively. RESULTS: After the treatment, BMI,
      WHR, FGS and OV were reduced significantly in both medication and abdominal
      acupuncture groups (P < 0.05), while MF of the two groups increased evidently (P
      < 0.05), and the effects of abdominal acupuncture group were significantly
      superior to those of medication group in down-regulating BMI, WHR and
      upregulating MF (P < 0.05). Regarding the reproductive hormons, serum LH, LH/FSH
      and T levels in the two groups decreased significantly (P< 0.05), and the effect
      of abdominal acupuncture was superior to that of medication group in reducing
      serum T level (P < 0.05). Following the treatment, FBG, BG and FIN and INS
      contents 2 h after meal,and Homa IR in both medication and abdominal acupuncture
      groups all decreased considerably (P < 0.05), but without significant differences
      between them (P > 0.05). Regarding the blood lipid levels after the treatment,
      serum TC, TG, and LDL-C levels of the two groups decreased significantly (P <
      0.05), while serum HDL-C level increased remarkably (P<0.05), without significant
      differences between the two groups in these indexes (P > 0.05). CONCLUSION:
      Abdominal acupuncture treatment can improve the endocrine and metabolic function
      of patients with obesity-type PCOS.

PMID- 21090335
TI  - [Clinical observation on acupuncture treatment of 150 cases of post-stroke
      depression according to syndrome differentiation].
AB  - OBJECTIVE: To observe the clinical therapeutic effect of acupuncture in the
      treatment of post-stroke depression (PSD) in the light of syndrome
      differentiation. METHODS: A total of 300 PSD patients were randomized into
      acupuncture group and medication group, with 150 cases in each group. For
      patients of acupuncture group,Sishencong (EX-HN 1), Baihui (GV 20), Shenting (GV
      24), etc. were punctured combined with other acupoints according to different
      syndromes, once daily for 2 months. For patients of medication group, fluoxetine
      (20 mg/d) was administered orally,continuously for 2 months. Hamilton's
      depression scale (HAMD) was used to evaluate changes of PSD patients' state after
      the treatment. RESULTS: After the treatment, the scores of HAMD in both groups
      decreased significantly (P < 0.05), and that of acupuncture group was remarkably
      lower than that of medication group (P < 0.05). Of the two 150 PSD patients in
      medication and acupuncture groups, 35 (23.3%) and 16 (10.7%) cases were cured, 82
      (54.7%) and 41 (27.3%) had a marked improvement, 17 (11.3%) and 57 (38.0%) had an
      improvement, and 16 (10.7%) and 36 (24.0%) were ineffective, with the total
      effective rates being 89.3% and 76.0% respectively. Chi-square test showed that
      the therapeutic effect of acupuncture was significantly superior to that of
      medication group (P < 0.05). CONCLUSION: Acupuncture is effective in improving
      post-stroke depression in PSD patients.

PMID- 21090336
TI  - [The location of Ciliao (BL 32) acupoint by three-dimensional reconstruction of
      computed tomography in women].
AB  - OBJECTIVE: To determine the location of Ciliao (BL 32) by the help of three
      dimensional (3-D) surface reconstruction of computed tomography (CT) so as to
      provide a reference for clinical application. METHODS: A total of 106 female
      volunteer subjects were enrolled in the present study. A CT scanner was used to
      scan the subjects' pelvis, and the collected image data was processed by
      Dextroscope workstation. The distances and angels of Ciliao(BL 32) in the 3-D
      space were measured. RESULTS: A linear correlation existed between the inter
      iliac distance (L 1) and sacro-foremen distance (L 2, with the regression
      equation being Y = 20.219 + 0.25X), and between the sacro-iliac distance and
      sacral foremen-iliac distance (with the regression equation being Y = -14.007 +
      0.446X), which were used to determine the location of BL 32. A linear correlation
      also existed between the body weight and the needling depth (with the regression
      equation being Y = -18.893 + 0.988X). So, the suitably inserted straight depth of
      acupuncture needle could be determined according to the woman's body weight. The
      oblique angle of the 2nd sacral foremen was (30.08 +/- 4.26), and the depth of
      the 2nd sacral foramen was (20.13 +/- 2.11) mm. CONCLUSION: In accordance with
      the results obtained from CT 3-D reconstruction, oblique needling of an
      acupuncture needle for Ciliao (BL 32) is highly recommended.

PMID- 21090337
TI  - [Paying attention to the heat thermal sensitivity of moxibustion is the key for
      raising the curative effect].
AB  - When moxibustion is applied to a certain acupoint in the patient, a regional heat
      sensitive reaction may be found. In the present paper, the authors expound its
      conception and appearing regularities, its relationship with the "arrival of qi"
      of Chinese medicine, and its clinical application in guiding acupoint selection
      and heat-stimulation quantity. Heat sensitive reaction during moxibustion ("heat
      sensitive moxibustion") is frequently seen in people undergoing pathological
      conditions and correlates highly with the diseases. It characterizes in dynamic
      changes in the location along with the state of the disorders and in being not
      always to coincide with the standard meridian acupoint location. The heat
      sensitive phenomenon of moxibustion is one of the manifestations in the activated
      functional activities of meridian of Chinese medicine just like the arrival of
      the qi caused by acupuncture stimulation. It is also a sign of activation of the
      human endogenous functional regulative system. Therefore, thinking highly of the
      heat sensitive reaction of moxibustion is the key point for raising the curative
      effect in clinical practice.

PMID- 21090338
TI  - [Progress of experimental studies on the underlying mechanism of acupuncture
      treatment of migraine].
AB  - Migraine is a common problem in clinic, characterized by bilateral impulsive
      severe headache with some autonomic and neurological symptoms. Acupuncture is
      effective for relieving headache. In the present paper, the authors review recent
      development of experimental researches on the mechanism underlying acupuncture
      induced improvement of migraine from: 1) inhibiting neurogenic inflammation, 2)
      improving cerebro-microcirculation, and 3) regulating vasoactive substances. The
      authors also point out that the theory of voltage-gated ion channel has provided
      a new reference for further study about the effect of acupuncture on voltage
      gated ion channel of migraine animal models.

PMID- 21090339
TI  - [Holmium laser enucleation of the prostate].
AB  - Holmium laser enucleation of the prostate (HoLEP), as a new hi-tech introduced
      from abroad, may bring about exactly the same results as open surgery, and is
      even superior to transurethral resection of the prostate (TURP), especially in
      handling the front prostate, with its advantages of minimal invasiveness, better
      safety, shorter operation time, less blood loss, and quicker recovery, which can
      be achieved through peeling off the prostate alongside the external sphincter and
      getting it removed in three parts or as a whole. So far, the author has
      accomplished more than 3 000 surgeries using this technique, without any serious
      complications. Any patient that can accept anesthesia and endoscopic surgery can
      be treated by HoLEP. This article presents an overview of the methods, skills and
      key points of HoLEP, gives a comprehensive analysis of HoLEP based on the
      anatomic features of the internal and external prostate, and offers a detailed
      introduction of the requirements of the operator, criteria for the accomplishment
      of the operation, and prevention and management of surgical damages.

PMID- 21090340
TI  - [Construction of an oncolytic adenovirus expressing small hairpin RNA and
      targeting the SATB1 gene].
AB  - OBJECTIVE: To construct an oncolytic adenovirus with the DD3 promoter regulation,
      expressing small hairpin RNA and targeting the SATB1 gene (SATBI-shRNA), and to
      evaluate its potential for inhibiting the growth of human prostatic carcinoma
      cells (LNCaP) in vitro. METHODS: SATB1-shRNA expression cassettes containing the
      H1 promoter were produced by PCR from pSilencer3. 1-SATB1 and inserted into the
      pZD55 vector, and the recombinant plasmid pZD55-SATB1-shRNA was constructed,
      pZD55SATB1-shRNA and pZXC2-DD3-E1A were digested with EcoRV and Xba I , and the
      obtained expression cassettes linked each other to construct the recombinant
      plasmid pDD3-ZD55-SATB1, which was cotransfected with the pBHGE3 packaging
      plasmids mixture into 293 cells by Effectence. The recombined adenoviruses DD3
      ZD55-SATB1 were identified by PCR. Viruses were propagated on HEK293 cells and
      purified by standard techniques, and the functional PFU titers determined by
      plaque assay on 293 cells. The antitumor potential of DD3-ZD55-SATB1 to LNCaP was
      evaluated by the crystal violet dye method. The expression level of the E1A gene
      was detected by Western blot, and that of the SATB1 gene in the adenovirus
      infected LNCaP cells by both Western blot and RT-PCR. RESULTS: An oncolytic
      adenovirus expressing SATB1-shRNA with the DD3 promoter regulation, DD3-ZD55
      SATB1, was constructed successfully, whose functional PFU titer was 1.2 x 10(10)
      PFU/ml. DD3-ZD55-SATB1 showed an obvious cytopathic effect and a selective
      expression of E1A in the adenovirus-infected LNCaP cells; it exhibited a high
      LNCaP-targetability and specific SATB1-silencing effect. CONCLUSION: The
      successful construction of the oncolytic adenovirus DD3-ZD55-SATB1 offers a new
      tool for researches on the gene therapy for human prostate cancer.

PMID- 21090341
TI  - [Changes of semen quality in Chinese fertile men from 1985 to 2008].
AB  - OBJECTIVE: To analyze the changes of semen quality in Chinese fertile men during
      the past 24 years. METHODS: We reviewed the literature on the sperm quality of
      Chinese fertile males published from 1985 to 2008, collected relevant data, and
      analyzed the changes in semen volume, sperm density, and total sperm count by
      linear regression. RESULTS: There were no significant changes either in semen
      volume during the period of 1985-2008 (P >0. 05) , or in sperm density and total
      sperm count from 1985 to 1994 (P > 0.05). However, significant decreases were
      observed during the latter 14 years in sperm density (from 81.5 x 10(6)/ml in
      1995 to 66.7 x 10(6)/ml in 2008, with a mean annual reduction of 1.40%) and total
      sperm count (from 257.2 x 10(6) in 1995 to 185.9 x 10(6) in 2008, with a mean
      annual reduction of 2. 15%) (P < 0.05). CONCLUSION: The semen quality of Chinese
      fertile men showed no significant changes from 1985 to 1995, but evidently
      declined from 1995 to 2008, which may be attributed to the aggravated
      environmental pollution induced by heavy chemical industry.

PMID- 21090342
TI  - [Expression of COX-2 in different human prostate cancer cell lines and its
      significance].
AB  - OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) in different
      prostate cancer (PCa) cell lines and its role in the acquisition of invasive and
      metastatic potentials of PCa. METHODS: We detected the expressions of COX-2 in
      prostate cancer cell lines LNCaP, C4-2, IF11, IA8 and PC-3 with different
      metastatic potentials by Western blotting and RT-PCR, and analyzed their roles in
      the invasion and metastasis of different PCa cell lines. RESULTS: Western
      blotting and RT-PCR showed that the expression of the COX-2 protein was high in
      PC-3, but absent in IF11, IA8, LNCaP and C4-2 (P < 0.05), and it was consistent
      with the expression of COX-2 mRNA. CONCLUSION: COX-2 expresses differently in PCa
      cell lines with different metastatic potentials. The overexpression of COX-2 may
      be associated with the high invasion and metastasis of PC-3, but not with the
      metastasis of other cell lines.

PMID- 21090343
TI  - [Expressions of phospho-Erk1/2 and phospho-Akt1 in the corpus cavernosum of aged
      rats].
AB  - OBJECTIVE: Nitric oxide (NO) is a key factor for penile erection. Its generation
      is mainly regulated by nitric oxide synthase (NOS), while both phospho-Erkl/2 (P
      Erkl/2) and phospho-Aktl (P-Aktl) can affect the expression and activity of NOS
      and consequently penile erection. This experiment aimed to study the expressions
      of P-Erkl/2 and P-Aktl in the corpus cavernosum and their possible roles in
      erectile dysfunction in aged rats. METHODS: We included 10 two-month-old male SD
      rats in Group A and another 10 eighteen-month-old ones in Group B, measured the
      levels of serum testosterone, and detected the expressions of P-Erkl/2 and P-Aktl
      in the corpus cavernosum by immunohistochemistry and RT-PCR. RESULTS: Compared
      with Group A, Group B showed a significantly decreased level of serum
      testosterone (9.57 +/- 1.57 nmol/L vs 4.73 +/- 0.94 nmol/L, P < 0.05), and
      remarkably increased mRNA expressions of P-Erk1 and P-Erk2 and protein expression
      of P-Erkl/2 (0.47 +/- 0.09, 0.61 +/- 0.11 and 7.50 +/- 1.81 vs 0.95 +/- 0.06,
      0.92 +/- 0.05 and 32.09 +/- 8.45, P < 0.05). But there were no significant
      differences in the mRNA and protein expressions of P-Akt1 between the two groups
      (0.97 +/- 0.04 and 11.67 +/- 5.61 vs 0.94 +/- 0.05 and 10.93 +/- 3.06, P > 0.05).
      CONCLUSION: The overexpression of P-Erk1/2 in the corpus cavernous may be one of
      the important mechanisms of aging-related erectile dysfunction.

PMID- 21090344
TI  - [Auto-dendritic cell vaccines pulsed with PSA, PSMA and PAP peptides for hormone
      refractory prostate cancer].
AB  - OBJECTIVE: To investigate the clinical safety and effects of auto-dendritic cells
      pulsed with HLA-A201-binding peptides prostate-specific antigen (PSA) , prostate
      specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP) in the
      treatment of hormone-refractory metastatic prostate cancer (HRPC). METHODS:
      Sixteen HRPC patients with positive HLA-A201 were enrolled and their monocytes
      isolated and induced into dendritic cells with the combination of rhGM-CSF and
      rhIL4. The patients were inoculated subcutaneously near the inguinal region with
      auto-DCs pulsed with peptides PSA (KLQCVDLHV) , PSMA (ALDVYNGL L) and PAP
      (LLHETDSAV) every 2 weeks for 4 times, and the immunological and clinical
      responses were examined within 1 -2 weeks after the final vaccination. RESULTS:
      Vaccination of dendritic cells was well tolerated and no toxicity was observed.
      The cytokine levels in the serum such as IL-2, IL-12 and IFN-gamma were
      significantly increased after the vaccination (P < 0.01). The delayed type hyper-
      sensitivity (DTH) test was positive in 4 of the patients (4/11), the percentage
      of antigen-special IFN-gamma+ CD8+ T increased in 5 (5/11), the level of the
      tumor marker PSA decreased in 6 (6/16) , hydrops abdominis reduced in 1 (1/16),
      and the size of the cervical lymph node lessened in 1 (1/16). Three patients
      showed partial remission (PR), 7 stability of the disease (SD), and the other 6
      progression of the disease (PD). CONCLUSION: Auto-DC vaccines loaded with PSA,
      PSMA and PAP peptides, capable of eliciting specific immune responses in HRPC
      patients, is a safe and effective option for the treatment of advanced HRPC.

PMID- 21090345
TI  - [Neuropeptide oxytocin and male infertility].
AB  - OBJECTIVE: To analyze the level of the oxytocin (OT) and the expression of
      oxytocin receptor (OTR) in males with idiopathic infertility. METHODS: Sixty-five
      infertile males aged 20 -45 years were divided according to their semen
      parameters into an idiopathic oligozoospermia group (OG, n = 20), an idiopathic
      asthenozoospermia group (AG, n = 25), and an idiopathic oligoasthenozoospermia
      group (OAG, n = 20). Another twenty 20-45 years old healthy male volunteers with
      a natural childbearing history were included in the control group (CG). All the
      subjects were detected for the contents of luteinizing hormone (LH), follicle
      stimulating hormone (FSH) , testosterone (T) and OT, and analyzed for the
      expression of OTR by sequencing the functional region of the OTR promoter (OTRP),
      OTR-mRNA, and OTR-COOH terminus. The gene sequences were compared using DNASTAR
      MegAlign, Western blot values changed into enumeration data, and all the data
      analyzed by one-way ANOVA and Dunnette's multiple range t-test. RESULTS: A
      significantly lower content of OT was observed in CG ( [79.30 +/- 3.83] pg/ml)
      than in OG ([118.53 +/- 7.69] pg/ml, AG ([108.81 +/- 5.66] pg/ml) and OAG
      ([103.71 +/- 4.54] pg/ml) (F(0.05/2[2,82]) = 8.29, P < 0.01). The content of LH
      was significantly lower in AG ([4.26 +/- 0.31] IU/L) and OAG ([4.55 +/- 0.40]
      IU/L) than in OG ([6.77 +/- 0.57] IU/L) and CG ([7.19 +/- 0.50] IU/L) (F(0.05/2
      [2,82]) = 11.64, P < 0.01), and so was the content of FSH in AG ( [5.02 + 0.39]
      IU/L) than in CG ([8.91 +/- 0.91] IU/L), OG ([11.86 +/- 1.76] IU/L) and OAG
      ([8.82 +/- 1.03] IU/L) (F(0.05/[2,82]) = 7.22, P < 0.01). There were no
      significant differences in the T content among the four groups (F(0.05/2[2,82] =
      0.42, P = 0.739). No evident gene mutation was found in OTRP and OTR-mRNA gene
      sequencing. Human OTRs in the lymphocytes were monomers and oligomers, mostly
      tetramers and hexamers. There were obviously more monomers in AG (0.41 +/- 0.03)
      and OAG (0.13 +/- 0.01) than in OG (0.05 +/- 0.004) and CG (0.05 +/- 0.003)
      (F(0.05/2[2,82]) = 115.50, P < 0.01), while the number of oligomers was markedly
      decreased in 20% of the cases in AG. CONCLUSION: Significant differences in the
      content of OT and expression of OTR between fertile and infertile men suggested
      an association of OT with male infertility. The decreased expression of OTR
      oligomers and increased expression of monomers may be related to idiopathic
      asthenozoospermia, which has provided a new insight into the pathogenesis and
      treatment of male infertility.

PMID- 21090346
TI  - [Bipolar transurethral resection of the prostate versus monopolar transurethral
      prostatectomy: a pathological study in a canine model].
AB  - OBJECTIVE: To compare the postoperative depths of the coagulation zones and
      pathological changes between bipolar transurethral resection of the prostate with
      plasmakinetic energy (PKRP) and monopolar transurethral prostatectomy (TURP) in
      canines. METHODS: Twenty-five male dogs were randomly divided into a PKRP group
      (n = 12), a TURP group (n = 12) and a sham-operation control group (n = 1). The
      dogs were sacrificed, their prostates harvested at 0 week (immediately after
      surgery), 1 week, 2 weeks and 8 weeks postoperatively and sectioned for
      pathologic analysis and measurement of the coagulation zones. RESULTS: At 0, 1
      and 2 weeks after the operation, the coagulation depths were (237.73 +/- 20.12)
      microm, (113.03 +/- 16.65) microm and (106.01 +/- 16.36) microm in the PKRP
      group, and (200.75 +/-19.34) microm, (129.46 +/- 17.81) microm and (116.04 +/-
      25.67) microm in the TURP group (P < 0.01). At 8 weeks, the coagulation zones
      completely peeled off and the wounds were covered by regenerated urothelial in
      both of the groups. At 0, 1, 2 and 8 weeks, different inflammatory reactions were
      observed in the prostates of the PKRP and TURP groups, with some glandular lumens
      beneath the coagulation zones expanded and epithelia damaged. However, none of
      these phenomena occurred in the sham-operation control group. CONCLUSION:
      Pathologically, PKRP and TURP inflicted basically similar effects on the prostate
      of the canine. However, the coagulation zone was deeper intraoperatively and
      became thinner postoperatively with the former than with the latter, which
      suggests that PKRP causes less bleeding and less penetrative thermal damage than
      TURP.

PMID- 21090347
TI  - [High-frequency color Doppler ultrasonography: valuable for diagnosis of
      polyorchidism].
AB  - OBJECTIVE: To investigate the application value of high-frequency color Doppler
      ultrasonography in the diagnosis of polyorchidism. METHODS: We retrospectively
      studied 6 cases of polyorchidism diagnosed by ultrasound, 5 of which were
      pathologically confirmed, and analyzed the sonographic and clinical findings.
      RESULTS: All the 6 cases were triorchidism, 4 located in the scrotum, and 2 in
      the same groin with indirect hernia. The supernumerary testis was linked to the
      epididymis in 3 cases, 1 accompanied with repeated epididymis and vas deferens,
      and 2 connected to no vas deferens and epididymis. Color Doppler ultrasonography
      revealed blood flow signals in 4 cases, but not in the other 2. CONCLUSION:
      Polyorchidism has typical sonographic appearances, and high-frequency color
      Doppler ultrasonography plays an important role in its diagnosis.

PMID- 21090348
TI  - [Serum proteomic study of prostate cancer with bone metastasis].
AB  - OBJECTIVE: To screen serum biomarker candidates in prostate cancer with bone
      metastasis by two-dimensional gel electrophoresis (2-DGE) and mass spectrometry.
      METHODS: Serum samples were obtained from 5 prostate cancer patients with bone
      metastasis, and another 5 without it. After depletion of the most abundant
      protein albumin from the serum, the samples were separated by 2-DGE and analyzed
      with the ImageMaster 2D Platinum software. The differentially expressed protein
      spots in the serum of those with bone metastases were identified by peptide
      fingerprinting with matrix-assisted laser desorption/ionization time of flight
      mass spectrometry (MALDI-TOF-MS). RESULTS: Compared with the serum samples from
      those without bone metastasis, 10 protein spot-features were found to be
      significantly increased and 5 significantly decreased, and the 3 identified
      proteins, Zn-alpha2-glycoprotein (ZAG), haptoglobin and apolipoprotein C-III,
      were all increased in the bone-metastasis group. CONCLUSION: The combination of 2
      DGE and mass spectrometry is an ideal platform and an effective means for the
      differential proteomic analysis of human sera. The identified proteins involved
      in the formation and progression of prostate cancer bone metastasis might be
      applied as biomarkers for bone metastasis from prostate cancer.

PMID- 21090349
TI  - [Effects of finasteride on hematuria associated with benign prostatic
      hyperplasia: a meta-analysis].
AB  - OBJECTIVE: To systematically evaluate the effects of finasteride on hematuria
      associated with benign prostatic hyperplasia (BPH). METHODS: We electronically
      searched MEDLINE (December 1966-April 2009), EMBASE (December 1974-April 2009),
      The Cochrane Library (Issue 1, 2009), CNKI (December 1994-April 2009), VIP
      (December 1989-April 2009) and CBM (December 1978-April 2009) , and handsearched
      several relevant journals as well. Randomized controlled trials were assessed
      with the methods recommended by the Cochrane Collaboration. The data were
      screened and systematically analyzed by at least two reviewers independently
      using the RevMan 5.0 software. RESULTS: Compared with the placebo control group,
      the finasteride group showed a significantly decreased incidence of hematuria
      during the 12 months follow-up period (OR 0.11, 95% CI: 0.06-0.21, P < 0.05).
      CONCLUSION: Finasteride has desirable therapeutic and preventive effects on BPH
      associated hematuria. More well-designed multicentered randomized controlled
      trials of large sample size are invited to provide further evidence for this
      conclusion.

PMID- 21090350
TI  - [Penile and scrotal skin flaps: first choice for urethroplasty in the treatment
      of hypospadias].
AB  - OBJECTIVE: To explore the feasibility of the treatment of hypospadias with penile
      and scrotal skin flaps. METHODS: Twenty-three hypospadias patients aged 3.5-19
      (mean 6. 8) years underwent urethroplasty with penile and scrotal skin flaps. All
      were followed up for 6 years and analyzed retrospectively. RESULTS: Of the total
      number of patients, 21 (91.3%) succeeded in one operation and the other 2
      developed complications, including urethral fistula and urethral structure.
      CONCLUSION: Penile and scrotal skin, advantageous for its adequacy, rich blood
      supply and contribution to high success rate of surgery, is believed to be the
      first choice for urethroplasty in the treatment of hypospadias.

PMID- 21090351
TI  - [Testicular torsion with atypical symptoms: seven cases report and review of the
      literature].
AB  - OBJECTIVE: To uplift the level in the early diagnosis and treatment of testicular
      torsion with atypical symptoms. METHODS: Retrospective analysis of 7 cases
      testicular torsion with atypical symptoms and review of the related literature
      were performed. RESULTS: Seven patients of testicular torsion came to the
      emergency department with back pain, among which 5 cases were received the
      detorsion successfully and 1 case underwent orchiectomy operation. The other
      patient given up surgery because of his family and himself refused to.
      CONCLUSION: The attending doctor must firstly check the testicles when the
      patient complained of back pain as the first symptom, so as to avoid
      misdiagnosis. As soon as testicular torsion was suspected, urgent surgical
      exploration should be performed immediately.

PMID- 21090352
TI  - [Advances in identification of semen stains].
AB  - Stain identification has long been a task in forensic biology. The identification
      of semen stain, one of the most common human stains, can provide crucial
      information for crime scene reconstruction and forensic investigation.
      Traditional detection of semen stain depends largely on the microscopic
      identification of spermatozoa, enzyme activity-based methods or antigen-antibody
      reactions. These morphological, proteinological and zymological approaches,
      however, are apparently inadequate in identifying tiny, admixed, degraded or
      contaminated samples. With the development of transcriptomics and epigenetics,
      many semen-specific mRNA markers, such as protamine-1 (PRM1) and -2 (PRM2), have
      been applied to semen and semen stain identification. Messenger RNA profiling
      shows great promise in identifying tissues as demonstrated by the recognition of
      specific markers. Further more, studies on tis-sue-specific differential DNA
      methylation will provide a scrumptious way of identifying difficult samples.

PMID- 21090353
TI  - [Application of iTRAQ in proteomic study of prostate cancer].
AB  - Amine-specific isobaric tagging (iTRAQ) reagents, as a new class of isobaric
      reagent, were developed in 2004, which, combined with liquid chromatography and
      tandem mass spectrometry (LC-MS/MS) , have been applied to the identification and
      quantification of proteins in a wide range of biological samples, including
      bacteria, yeasts, human tissues, cells, and fluids. As a new method of
      quantitative proteomics, the technique of iTRAQ allows for the quantitative
      analysis of four samples simultaneously and displays its advantages of high-flux,
      food reproducibility, and high sensitivity; it also provides a potential
      technological platform for studying the mechanisms of the development and
      progression of prostate cancer.

PMID- 21090354
TI  - [Updated detection of the function of sperm plasma membrane].
AB  - The sperm plasma membrane is rich in polyunsaturated fatty acids and a variety of
      proteins, and its function is associated with sperm capacitation, acrosome
      reaction and sperm-egg fusion. Sperm fertilizability can be predicted by
      detecting the function of the sperm plasma membrane, which is performed mainly
      with the following five techniques: sperm hypoosmotic swelling test, Eosin gamma
      water test, sperm membrane lipid peroxidation determination, seminal plasma
      superoxide dismutase determination, and flow cytometry. The evaluation of the
      function of sperm plasma membrane can be applied in detecting semen quality,
      selecting semen centrifugation, assessing the quality and fertilizability of sex
      sorted sperm, improving cryopreservation, and guiding the optimization of
      intracytoplasmic sperm injection. This review presents an update on the
      principles, methods and steps of the detection of sperm plasma membrane function,
      as well as an overview of its status quo and application.

PMID- 21090355
TI  - [Anti-fertility effect of Tongbi composition and its reversibility in male rats].
AB  - OBJECTIVE: To study the anti-fertility effect of maximum-dose Tongbi Composition
      and its reversibility in male rats. METHODS: Thirty-six male SD rats were equally
      randomized into a control group and a medication group, the former given normal
      saline at 10 ml/(kg x d), while the latter treated with Tongbi Composition at 10
      g/(kg x d), both for 60 days. Half the rats of each group were sacrificed
      randomly at the cessation of treatment, and the rest killed at 72 days after it.
      The relative testis weight, testis volume, sperm concentration and sperm motility
      were measured, and the pathological changes in the testicular tissue observed
      under the optical microscope. RESULTS: After 60 days of treatment, no
      statistically significant differences were found between the two groups in the
      relative testis weight, testis volume and sperm concentration (P > 0.05) , and
      the sperm motility of the medication group dropped to zero, but it was restored
      to normal at 72 days after drug withdrawal. Almost no lesions were observed in
      the testis tissue of the medication group. CONCLUSION: The short-term use of
      Tongbi Composition at the maximum clinical dose has an obvious anti-fertility
      effect, but it is reversible.

PMID- 21090356
TI  - [Comparative efficacy of various variants of pancreaticoduodenal resection
      according to the results of early postoperative period].
AB  - Pancreatoduodenal resection (FOR) was performed in 131 patients: in 105--for
      pancreatoduodenal zone cancer and in 26--for fibrous chronic pancreatitis. The
      elaborated procedure for pancreatojejunoanastomosis formation, performed on
      reconstructive stage of PDR, secures the total complications rate lowering,
      comparing with such in conventional procedure with end to end aniastomosis
      suturing and after terminolateral anastomosis formation in 1.42 and 1.62 times,
      according. Cryodestruction secures the lowering of the total complications rate
      and the complications rate while usinn various variants of the PDR on
      reconstruction state.

PMID- 21090358
TI  - [Ultrasonographic diagnosis and characteristic of postoperative accumulations of
      a liquid].
AB  - Ultrasonographic semiotics of extraorgan localized postoperative accumulations of
      a liquid occurring after performance of interventions on a liver was studied up.
      There was established the dependence of their localization on the operation kind.
      The differential diagnosis algorithm of some pathologic conditions (haematoma,
      biloma, seroma) was elaborated.

PMID- 21090357
TI  - [Miniinvasive interventions for focal liquid accumulations in region of pancreas
      and surrounding tissues].
AB  - The results of treatment of 264 patients, suffering an acute and chronic
      pancreatitis, are analyzed. In 30% of observations the liquid peripancreatic
      accumulations observed have had regressed under the influence of complex
      conservative therapy and in other--there were performed transcutaneous punctures
      under ultrasonographic guidance, the cysts drainage, using laparoscopic method.
      The recurrence free postoperative period had lasted not less than 3 months.

PMID- 21090359
TI  - [Determination of D-dimer in the blood using the Simplired method in patients
      with possible diagnosis of the deep veins thrombosis during urgent abdominal
      surgery].
AB  - The results of treatment of 78 patients, operated in the clinic in 2008-2010 yrs,
      are adduced. The sensitivity, specificity and the precision values were
      determined for diagnostic method in deep veins thrombosis (DVT). The method was
      based on investigation of the products of degradation content of the transversely
      sutured fibrine (D-dimer) and its dynamics in the blood of patients. D-dimer was
      determined, using express-method of the erythrocytes agglutination identification
      with application of SimpliRED technology in the whole blood. In 16 (20.5%)
      patients DVT was revealed within vena cava inferior basin, of them in 7 (43.7%)
      patients the course of thrombosis was asymptomatic, and the disease presence have
      had become suspected after obtaining of the D-dimer test positivity and was
      confirmed by ultrasonographic angioscanning. In 43 (55.1%) patients of the
      investigated group the D-dimer test positivity was noted. In all the patients,
      suffering phlebothrombosis, the test was extremely positive, presented by the
      erythrocytes agglutination on the 5-20th second and long-term presence of D-dimer
      during (17 +/- 6) days, at average. In 14 (87.5%) patients the application of
      direct anticoagulants was stopped after the test negative results obtaining.
      Rethrombosis and pulmonary artery thronboembolism (according to clinical
      investigation) did not occur.

PMID- 21090360
TI  - [The risk factors of the respiratory complications occurrence after tracheal
      extubation in the surgery of the thyroid gland].
AB  - There were examined 400 patients after tracheal extubatton performance, to whom
      thyroidal surgery was done. The rate and causes of occurrence of respiratory
      complications were studied up. Laryngeal oedema was revealed in 5.5% patients,
      injury of laryngeal nerves--in 3.0%, postoperative hemorrhage--in 1.2%. For the
      respiratory complications occurrence the risk factors are following: thyroidal
      cancer, polynodous goiter, subtotal thyroidectomy, extrafascial thyroidectomy,
      the operation duration, hard trachreal intubatlon, the patients age and gender.

PMID- 21090361
TI  - [Sclerotherapy in surgical correction of varicocele].
AB  - The method of intraoperative sclerotherapy, using 40% glucose solution, for
      varicocele surgical treatment was proposed. Diathermocoagulation of all visible
      accompanying veins was conducted for reduction of the varicocele recurrence rate.
      The recurrence is reduced to 6.6%.

PMID- 21090362
TI  - [Complications of the finger osteosynthesis using Kirschner's wires in arterial
      inflow disorder].
AB  - At an osteosynthesis of Kirshner wires to one of widespread complications is
      their spontaneous migration that leads to formation of bone deformation or to
      necessity of application of less effective kinds of an immobilization. In
      posttraumatic change of arterial inflow to hand and fingers leads to an oxygen
      level reduction in tissues, their chronic ischemia and to increase of a lactate
      and pyruvate contents in peripheral blood that can influence on Kirshner wires.
      Spontaneous migration of Kirshner wires from bones of fingers and decrease of
      their fixing in the bones is characteristic for patients with the expressed
      posttraumatic infringement of arterial inflow. This phenomenon can be explained,
      in particular, of acidity of peripheral blood change owing to considerable
      reduction arterial blood flow and secondary changes in bone and metal pin contact
      surface.

PMID- 21090363
TI  - [Reality of dying in conditions of Preshov region].
AB  - Dying, but not the death, is an essential problem. The more we believe that death
      ends everything, the more we fear from death. All religions want to cut this
      fear. They highlight that present life continues and human spirit lives further
      on, in another postmortem dimension. Authors evaluated death of 142 patients,
      among which 45 (32%) died at home, 74 (52%) in hospital, 34 (24%) among family
      relatives and 56 (39%) without the presence of relatives. Most of the dying
      patients wish to stay with their family. If this wish cannot be fulfilled, then a
      palliative care seems to be the most suitable alternative for an individual in
      terminal stage in modern society. In the Preshov region, there is a lack of
      hospices and palliative care does not cover the needs of terminally ill patients.

PMID- 21090365
TI  - [Tension-free "plug" method in the treatment of femoral hernia using open access:
      evolution of views].

PMID- 21090364
TI  - [Treatment of traumatic arterio-venous fistula].

PMID- 21090366
TI  - [Sudden mid-foot pain in an eight-year-old patient].

PMID- 21090367
TI  - [Biologist Robert G. Edwards honored. Nobel Prize in Medicine for the devil's
      work].

PMID- 21090368
TI  - [Telemonitoring. Patient contact: what can be accomplished electronically?].

PMID- 21090369
TI  - [D-dimer determination in thrombosis diagnosis. A diagnostic test with pitfalls].

PMID- 21090370
TI  - [Psychological comorbidity in tinnitus. Noise in the ear - torture for the
      psyche].

PMID- 21090371
TI  - [Drug safety in clinics. Who monitors drug interactions?].

PMID- 21090372
TI  - [Sexually must not be a taboo. Even mentally handicapped patients long for love
      and intimacy (interview by Maria Weiss)].

PMID- 21090373
TI  - [Naturopathy consultation. Infection with influenza].

PMID- 21090374
TI  - [Adjuvant cancer therapy].

PMID- 21090375
TI  - [Adjuvant treatment in hormone receptor positive breast cancer].

PMID- 21090376
TI  - [Managing side effects of androgene deprivation in prostate cancer].

PMID- 21090377
TI  - [Food allergy].

PMID- 21090378
TI  - [Tachyarrhythmia: acute and long-term therapy in atrial fibrillation].

PMID- 21090379
TI  - [Compliance-problems in antihypertensive therapy].

PMID- 21090380
TI  - [Management of fever in children younger then 3 years].
AB  - Fever represents a normal physiological response as a result of the introduction
      of an infectious agent producing exogenous and endogenous pyrogenes influencing
      the central set point of body temperature. This response is an important
      immunological defence. Fever can be defined as any elevation of body temperature
      above 38 degrees C. Infancy body temperature should be measured rectal. Fever is
      mostly caused by a benign viral infection, but it can be an indicator of a major
      illness such as meningitis, septicaemia, pneumonia. The risk for severe evolution
      depends on the clinical context and the age of the infant. Most predictive for
      major illness are situations in which infants are younger than 3 months with body
      temperature > or = 38 degrees C, infants between 3 and 6 months with body
      temperature > or = 39 degrees C, and children of any ages with critical clinical
      signs. Those patients should be seen by a medical doctor as soon as possible.
      Height and duration of fever are no predictive parameters for major illnesses.
      Repeated observation of the feverish child is very important in order to follow
      any evolution. Uncomplicated fever is harmless and should not be treated. If
      necessary, we prefer acetaminophen (paracetamol), given orally except in cases of
      vomiting. Antipyretics will not affect the cause of fever, sometimes they might
      make the diagnosis of the underlying cause difficult, but they may have an effect
      on discomfort for the child. If antipyretics have been given, repeated
      observations stay important. Postvaccineal fever should not be treated in a
      different way. Febrile convulsion is a common outcome of childhood febrile
      illness. Adverse effects are rare. The use of antipyretics cannot prevent initial
      or recurrent febrile convulsions and they should not be used for this purpose.

PMID- 21090381
TI  - [Influenza vaccines and their evidenced based efficacy].

PMID- 21090382
TI  - [Evaluation of the quality of counseling provided by community pharmacists to
      pregnant women].
AB  - OBJECTIVES: To evaluate the quality of counseling provided by community
      pharmacists to pregnant women. METHODS: Observational study. Three clinical
      scenarii were selected on the basis of frequent complaints during pregnancy and
      likely use of medications: (1) headache (2) nausea and vomiting (3) no complaint,
      but request of a pregnancy test and a decongestive medicine. Four simulated
      female patients presented themselves to a total of 26 community pharmacies and
      asked precise questions. The responses were transcribed, compared to the awaited
      responses, and after the initial conversation a semi-quantitative questionnaire
      was filled in by the pharmacist. RESULTS: No pharmacist proposed a drug
      considered to be contra-indicated during pregnancy. For most drugs, pharmacists
      knew whether the use during pregnancy was allowed or not. In contrast, too few
      questions were asked before dispensing medicines, non pharmacological options
      were most often omitted, and explanations relative to choice of therapy and
      dosage were usually very limited and sometimes inexistent or incorrect.
      CONCLUSIONS: This pilot study showed that pharmacist counseling on the medicines
      (not) to be taken during pregnancy is of good quality, but that there is room for
      improvement in the following: questions to be asked before dispensing medicines,
      non-pharmacological options, dosage information, and rationale for choosing a
      specific drug.

PMID- 21090383
TI  - [Medicine information for patients with a major depression at hospital
      discharge].
AB  - This article provides an overview of several parts of a doctoral thesis on
      medicine information for patients with a major depression at hospital discharge.
      A review of the international literature showed that medicine information can
      increase knowledge and adherence. Inpatients would like to receive more
      information on the medicines prescribed. The GIPPOZ-study showed positive results
      on a few economic outcomes when a differentiated approach in providing
      information on antidepressants was applied. Follow-up calls of participants of
      the GIPPOZ-study yielded interesting qualitative findings on problems and
      perspective after discharge from hospital. The hospital pharmacists stressed the
      individual approach of patients during the GIPPOZ-study. Practice and health
      policy suggestions were formulated. Health care professionals should provide more
      information to patients on their medicines. Policy makers should guarantee a
      structure so that health care professionals can fulfill their role as provider of
      medication information.

PMID- 21090384
TI  - Cancer among men on cholesterol-lowering diets: Experience from five clinical
      trials.

PMID- 21090385
TI  - Vascular and interventional radiology.

PMID- 21090386
TI  - Ophthalmology.

PMID- 21090387
TI  - Coronary atherectomy.

PMID- 21090388
TI  - Pediatric gastroenterology.

PMID- 21090389
TI  - Do no harm...is that good enough?

PMID- 21090390
TI  - Meeting of the WHO working group on polymerase chain reaction protocols for
      detecting subtype influenza A viruses - Geneva, June 2010.

PMID- 21090391
TI  - Fourth meeting of National Influenza Centres in the WHO Western Pacific Region -
      May 2010.

PMID- 21090392
TI  - Turkmenistan certified malaria-free.

PMID- 21090393
TI  - WHO Quantitative Immunization and Vaccine-Related Research meeting, October 2010 
      summary.

PMID- 21090394
TI  - Yellow fever surveillance and outbreak response: revision of case definitions,
      October 2010.

PMID- 21090395
TI  - Diagnosis and treatment of cutaneous paraneoplastic disorders.

PMID- 21090397
TI  - A costly diagnostic failure.

PMID- 21090396
TI  - Treating DVT: answers to 7 key questions.

PMID- 21090398
TI  - Generic drugs: the benefits and risks of making the switch.

PMID- 21090399
TI  - Which NSAID for your patient  with osteoarthritis?

PMID- 21090400
TI  - On graduate programs and their leaders.

PMID- 21090401
TI  - An interview with Professor Sandro Palla. Interviewed by Iven Klineberg.

PMID- 21090402
TI  - Our brain: the enemy.

PMID- 21090403
TI  - Special foreward. Perfluorinated alkylated substances.

PMID- 21090404
TI  - Computers in the library.

PMID- 21090405
TI  - Instability of firing threshold and "remote" activation in cortical neurons.

PMID- 21090406
TI  - Neuronal basis for the central action of chlorpromazine.

PMID- 21090407
TI  - Role of catalase in bioenergetic processes in livers of white rats.

PMID- 21090408
TI  - Muscle lesions in mice injected with isologous and homologous muscle extracts.

PMID- 21090409
TI  - Phagocytosis and synthesis of ribonucleic acid in human granulocytes.

PMID- 21090410
TI  - Development of immunologically competent cells in the rat.

PMID- 21090412
TI  - A computer programme for the analysis of human chromosomes.

PMID- 21090411
TI  - Phosphorylation of Escherichia coli alkaline phosphatase by substrate.

PMID- 21090413
TI  - Carbon tetrachloride toxicity and electron capture.

PMID- 21090414
TI  - Experimental infections of cattle with Fasciola hepatica. Challenge infections.

PMID- 21090415
TI  - Effect of the causal fungus of brown root rot of tomatoes on the hatch of the
      potato root eelworm, Heterodera rostochiensis Woll.

PMID- 21090416
TI  - Sensitization of HeLa cells containing 5-bromodeoxyuridine to ultra-violet light
      at different stages of the division cycle.

PMID- 21090417
TI  - Infectivity of trypanosomes derived from individual Glossina morsitans Westw.

PMID- 21090418
TI  - Formation and retention of the spermatozoan reservoir in the cervix of the
      ruminant.

PMID- 21090419
TI  - Model for DNA and protein interactions and the function of the operator.

PMID- 21090420
TI  - Ascorbate stimulation of RNA synthesis.

PMID- 21090421
TI  - Antiparallelism of chains in polyglycine II.

PMID- 21090422
TI  - Partial reversal of the thymineless state in vivo.

PMID- 21090423
TI  - Long term and short term effects on retention of a conditioned avoidance response
      in rats by treatment with long acting pitressin and alpha-MSH.

PMID- 21090424
TI  - Enzyme inactivation of aspermatogenic antigen.

PMID- 21090425
TI  - Action of pancreozymin preparations on gastric secretion.

PMID- 21090426
TI  - Steroids of invertebrates: the in vitro production of II-ketotestosterone and
      other steroids by the eggs of the slug, Arion ater rufus (Linn.).

PMID- 21090427
TI  - Effect of certain nitriles on cartilage synthesis in vitro.

PMID- 21090428
TI  - Activities of glycogen synthetase and UDPG-pyrophosphorylase in muscle of a
      patient with a new type of muscle glycogenosis caused by phosphofructokinase
      deficiency.

PMID- 21090429
TI  - Formation in vitro of a lipoprotein membrane masking lysozyme activity.

PMID- 21090430
TI  - Active immunization of chicks against Plasmodium gallinaceum by inactivated
      homologous sporozoites and erythrocytic parasites.

PMID- 21090431
TI  - Antimalarial activity of sulphonamides and a sulphone, singly and in combination
      with pyrimethamine, against drug resistant and normal strains of laboratory
      plasmodia.

PMID- 21090432
TI  - Artificial induction of transplantation viral antigens in the course of chemical
      carcinogenesis.

PMID- 21090433
TI  - Two antigenically distinguishable subclasses of human A myeloma proteins
      differing in their heavy chains.

PMID- 21090434
TI  - Colorimetric determination of guanidines in blood.

PMID- 21090435
TI  - Electron microscopy of the chemoreceptor cells of the carotid labyrinth of the
      toad.

PMID- 21090436
TI  - Neoplasm transplantation inhibition by uninvolved lymph tissue.

PMID- 21090437
TI  - Evidence for collagen in a fossil of the Lower Jurassic.

PMID- 21090438
TI  - Mechanism of binocular increase of discomfort to high luminance.

PMID- 21090439
TI  - Startle response of rats after the production of lesions at the junction of the
      mesencephalon and the diencephalon.

PMID- 21090440
TI  - Excess alpha chain synthesis relative to beta chain synthesis in thalassaemia
      major and minor.

PMID- 21090441
TI  - Regulation of serum fatty acids, free glycerol and acetoacetate during prolonged
      fasting in obese and lean people.

PMID- 21090442
TI  - In vitro destruction of human fibroblasts by non-immune lymphoid cells.

PMID- 21090443
TI  - Differentiation of the biological activities of phytohaemagglutinin affecting
      leucocytes.

PMID- 21090444
TI  - Lactic acid as a factor in the production of irreversibility in oligohaemic
      shock.

PMID- 21090445
TI  - Secretion and synthesis of amylase in the rat parotid gland after isoprenaline.

PMID- 21090446
TI  - Shope papilloma virus: a passenger in man and its significance to the potential
      control of the host genome.

PMID- 21090447
TI  - Strontium as a substitute for calcium in the process of transmitter release at
      the neuromuscular junction.

PMID- 21090448
TI  - Rapid light-induced potentials common to plant and animal tissues.

PMID- 21090449
TI  - Possible mechanisms of depression of cerebral phospholipid metabolism during a
      deficiency of body oxygen.

PMID- 21090450
TI  - Gases produced by human intestinal microflora.

PMID- 21090451
TI  - Turnover of individual phospholipid fractions in the rat brain during hypoxia.

PMID- 21090452
TI  - Miniature synaptic potentials in squid nerve cells.

PMID- 21090453
TI  - Input-output relation of a single synapse.

PMID- 21090454
TI  - Increased tolerance to intravenous hypertonic saline in patients with essential
      hypertension.

PMID- 21090455
TI  - Binding of choline acetyltransferase in the nerve ending particles of brain.

PMID- 21090456
TI  - Daily torpor in the marsupial smouse, Sminthopsis larapinta (Spencer).

PMID- 21090457
TI  - Increased histidine decarboxylase activity of rat lung in endotoxin shock.

PMID- 21090458
TI  - Mechanism of calcification in mammalian bone.

PMID- 21090459
TI  - Factor in serum inhibiting bone marrow mitoses after X-irradiation of the spleen.

PMID- 21090460
TI  - Post-irradiation changes in the deoxyribonucleoprotein complex in animal tissues
      as revealed by the action of heparin.

PMID- 21090461
TI  - Species specificity of prolactin.

PMID- 21090462
TI  - Stabilization of fluorescence in preparates treated by the fluorescent antibody
      technique.

PMID- 21090464
TI  - Vascular lesions due to obstruction of the vasa vasorum.

PMID- 21090463
TI  - Failure to change the antigenicity of skin grafts by incubation with allogeneic
      ribonucleic acid.

PMID- 21090465
TI  - Localization of an inhibitor preventing mammary tumour development in mice.

PMID- 21090466
TI  - Electron microscopy of Friend tumour cell with special reference to the influence
      of Friend virus immunity on Friend tumour cell.

PMID- 21090467
TI  - Growth inhibitor of hamster fibroblast cells.

PMID- 21090468
TI  - Influence of B.C.G. on experimental amyloidosis.

PMID- 21090469
TI  - Enzyme studies in human liver and adipose tissue.

PMID- 21090470
TI  - Anthocyanin in Dionaea muscipula Ellis (Venus flytrap).

PMID- 21090471
TI  - Stability of DNA in Escherichia coli B/r and B(s-1) irradiated with ultra-violet
      light.

PMID- 21090472
TI  - Reduced breakdown of rat liver microsomal ribonucleic acid after administration
      of cortisone.

PMID- 21090473
TI  - Quantitative determination of urinary indoxyl sulphate (indican) and the total
      content of basic compounds in the faeces of cattle in relation to
      hypomagnesaemia.

PMID- 21090474
TI  - Catecholamine binding protein: binding of tritium to a specific protein fraction
      of human plasma following in vitro incubation with tritiated noradrenaline.

PMID- 21090475
TI  - Formation of bradykinin from kallidin-10 by aminopeptidase B.

PMID- 21090476
TI  - Ontogeny of cattle haemoglobin.

PMID- 21090477
TI  - Antibacterial effect of fisetin and fisetinidin.

PMID- 21090478
TI  - Lysozyme granules and lysosome structures in cell culture.

PMID- 21090479
TI  - Serology of strains of Streptococcus faecalis which produce hyaluronidase.

PMID- 21090480
TI  - The coil planet centrifuge.

PMID- 21090481
TI  - Measurements of calcium-47 and strontium-85 in human subjects.

PMID- 21090482
TI  - Micro structures of dental enamel observed with the differential interference
      reflected light microscope.

PMID- 21090483
TI  - Maternal regulation of intra-uterine growth.

PMID- 21090484
TI  - Reversible transformation of lymphocytes in human leucocyte cultures.

PMID- 21090485
TI  - Organochlorine insecticide residues in complete prepared meals in Great Britain
      during 1965.

PMID- 21090486
TI  - Immunochemically significant fluoresceins: structure determination by nuclear
      magnetic resonance spectroscopy.

PMID- 21090487
TI  - Daily torpor induced in white-footed mice (Peromyscus spp.) by starvation.

PMID- 21090488
TI  - Timing of injection of pregnant mare's serum for the anoestrous breeding of ewes.

PMID- 21090489
TI  - Delay inflammatory due to catecholamines and serotonin.

PMID- 21090490
TI  - Blood sugar concentration after glucose tolerance test and simultaneous iron
      tolerance test.

PMID- 21090491
TI  - Effect of ingestion of milk on concentrations of blood alcohol.

PMID- 21090492
TI  - Extraction, purification and chemical determination of a hepatic factor inducing
      contraction of the spleen.

PMID- 21090493
TI  - Effects of alloxan diabetes, starvation and hypophysectomy on total
      phosphofructokinase activity in rat heart.

PMID- 21090495
TI  - Chemical studies on some Nigerian foodstuffs--"gari".

PMID- 21090494
TI  - Inhibition of gonadotrophin by a highly purified pineal peptide and by synthetic
      arginine vasotocin.

PMID- 21090496
TI  - Changes in platelet membranes possibly associated with platelet stickiness.

PMID- 21090497
TI  - Comparative action of methyl and isopropyl methane sulphonates on the peripheral
      leucocyte count in monkeys.

PMID- 21090498
TI  - Thermal resistance of Salmonella senftenberg.

PMID- 21090499
TI  - Hepatic antigen in sera from patients with liver disease.

PMID- 21090500
TI  - Effect of some insecticides on the hatching rate of hens' eggs.

PMID- 21090501
TI  - Experiments on eggs and adult specimens of Cyathostoma lari E. Blanchard, 1849.

PMID- 21090502
TI  - Conidiation of Neurospora crassa.

PMID- 21090503
TI  - Regular supply of large numbers of standard continuous line cells.

PMID- 21090504
TI  - Choice reaction time as a function of stimulus versus response relative frequency
      of occurrence.

PMID- 21090505
TI  - Nutritional requirements of mycelial growth and sporulation of several biocontrol
      fungi in submerged and on solid culture.
AB  - To develop fungal biopesticides, the nutritional requirements on available
      culture media that maximize mycelia and spore yields at low cost are essential
      for their mass-production. The objective of present study was to find the optimal
      combinations for the most mycelia yield in submerged and the highest spore yield
      on solid. Have a better understanding of their basic physiology, and have a
      better yield of mycelia and conidia with short time and low cost will help to
      provide valuable information for mass production and commercialization.

PMID- 21090506
TI  - An organic solvent-, detergent-, and thermo-stable alkaline protease from the
      mesophilic, organic solvent-tolerant Bacillus licheniformis 3C5.
AB  - Bacillus licheniformis 3C5, isolated as mesophilic bacterium, exhibited tolerance
      towards a wide range of non-polar and polar organic solvents at 45 degrees C. It
      produced an extracellular organic solvent-stable protease with an apparent
      molecular mass of approximately 32 kDa. The inhibitory effect of PMSF and EDTA
      suggested it is likely to be an alkaline serine protease. The protease was active
      over abroad range of temperatures (45-70 degrees C) and pH (8-10) range with an
      optimum activity at pH 10 and 65 degrees C. It was comparatively stable in the
      presence ofa relatively high concentration (35% (v/v)) of organic solvents and
      various types of detergents even at a relatively high temperature (45 degrees C).
      The protease production by B. licheniformis 3C5 was growth-dependent. The
      optimization of carbon and nitrogen sources for cell growth and protease
      production revealed that yeast extract was an important medium component to
      support both cell growth and the protease production. The overall properties of
      the protease produced by B. licheniformis 3C5 suggested that this thermo-stable,
      solvent-stable, detergent-stable alkaline protease is a promising potential
      biocatalyst for industrial and environmental applications.

PMID- 21090507
TI  - Microbiological and SYBR green real-time PCR detection of major Fusarium head
      blight pathogens on wheat ears.
AB  - Fusarium head blight (FHB) caused by several Fusarium species is one of the most
      serious diseases affecting wheat throughout the world. The efficiency of
      microbiological assays and real-time PCRto quantify major FHB pathogens in wheat
      ears after inoculation with F. graminearum, F. culmorum, F. avenaceum and F. poae
      undergreenhouse and field conditions were evaluated. The frequency of infected
      kernel, content of fungal biomass, disease severity and kernel weight were
      determined. To measure the fungal biomass an improved DNA extraction method and a
      SYBR Green real-time PCR were developed. The SYBR Green real-time PCR proved to
      be highly specific for individual detection of the species in a matrix including
      fungal and plant DNA. The effect of Fusarium infection on visible FHB severity,
      frequency of infected kernels and thousand-kernel mass (TKM) significantly
      depended on the Fusarium species/isolate. F. graminearum resulted in highest
      disease level, frequency of infected kernels, content of fungal biomass, and TKM
      reduction followed by F. culmorum, EF avenaceum and F. poae, respectively. The
      comparison of frequency and intensity of kernel colonization proved differences
      in aggressiveness and development of the fungi in the kernels. Only for F.
      graminearum, the most aggressive isolate, application of microbiological and real
      time PCR assays gave similar results. For the other species, the intensity of
      kernel colonization was lower than expected from the frequency of infection.

PMID- 21090508
TI  - Multiple copies of 16s rRNA gene affect the restriction patterns and DGGE profile
      as revealed by analysis of genome database.
AB  - The use of 16S rRNA gene has been a "golden" method to determine the diversity of
      microbial communities in environmental samples, phylogenetic relationships of
      prokaryotes and taxonomic position of newly isolated organisms. However due to
      the presence of multiple heterogeneous 16S rRNA gene copies in many strains, the
      interpretation of microbial ecology via 16S rRNA sequences is complicated.
      Purpose of present paper is to demonstrate the extent to which the multiple
      heterogeneous 16S rRNA gene copies affect RFLP patterns and DGG E profiles by
      using the genome database. In present genome database, there are 782 bacterial
      strains in total whose genomes have been completely sequenced and annotated.
      Among the total strains, 639 strains (82%) possess multiple 16S rRNA gene copies,
      415 strains (53%) whose multiple copies are heterogeneous in sequences as
      revealed by alignment, 236 strains (30%) whose multiple copies show different
      restrict patterns by CSP61 + Hinfl, MspI + Rsal or HhaI as analyzed in silico.
      Polymorphisms of the multiple copies in certain strains were further
      characterized by G + C% and phylogentic distances based on the sequences of V3
      region, which are linked to DGGE patters. Polymorphisms of a few strains were
      shown as examples. Using artificial communities, it is demonstrated that the
      presence of multiple heterogeneous 16S rRNA gene copies potentially leads to over
      estimation of the diversity of a community. It is suggested that care must be
      taken when interpreting 16S rRNA-based RFLP and DGGE data and profiling an
      environmental community.

PMID- 21090509
TI  - Biodiversity and monitoring of colorless filamentous bacteria in sulfide aquatic
      systems of North Caucasus region.
AB  - Bacterial mats in sulfide aquatic systems of North Caucasus are basically
      composed by the species of genera Thiothrix and Sphaerotilus. Additionally,
      several non-filamentous sulfur-oxidizing bacteria were isolated from the mats and
      several minor 16S rRNA phylotypes were found in clone libraries from these mats.
      The minor components were affiliated with Proteobacteria, Chlorobia,
      Cyanobacteria and Firmicutes. Even in an individual mat population heterogeneity
      of Thiothrix spp. was revealed by analysis of 16S rRNA gene and RAPD-PCR. Five
      Thiothrix isolates were described as new species Thiothrix caldifontis sp. nov.
      and Thiothrix lacustris sp. nov. In the Thiothrix-Sphaerotilus type of bacterial
      mat the proportion of dominant organisms might be influenced by sulfide
      concentration in the spring water. The higher sulfide concentration (more than 10
      mg/l) in the spring water is more favorable for the development of bacterial mats
      with dominant Thiothrix organisms than for Thiothrix-Sphaerotilus type of sulfur
      mat.

PMID- 21090510
TI  - Humidity-induced spectral shift in a cross-dispersion echelle spectrometer and
      its theoretical investigation.
AB  - The relationship between ambient relative humidity H and the position shift of a
      spectral line was investigated both experimentally and theoretically. An echelle
      based ICP emission spectrometer equipped with a CID detector was used for
      experimental verification of the derived model. The shift of a spectral line is
      quantitatively described by two defined spectral shift functions: delta lambda
      x(x, lamda, H) (in the x direction of the CID detector) and delta lambda y(y,
      lambda, H) (in the y direction of the CID detector). Experimental results
      indicate that delta lamda x(x, lambda, H) does not change with a variation in
      ambient relative humidity, but delta lamda y(y, lambda, H) does. A spectral shift
      equation, i.e., an empirical second-order polynomial equation, can be used to
      describe the relationship between delta lamda y(y, lambda, H) and H. Based on the
      classical dipole model, classical mechanics and electrodynamics the empirical
      spectral-shift equation involving delta lambda y(y, lambda, H) and H was
      theoretically deduced. The theoretical result is in good agreement with the
      experimental findings. The theoretical results indicate that the coefficients of
      the empirical spectral-shift equation are related to the basic physical
      parameters of materials and the geometric configuration of the echelle CID ICP
      AES, and also provide physical meaning to the coefficients of the empirical shift
      equation obtained experimentally.

PMID- 21090511
TI  - Comparison of home health and hospice care agencies by organizational
      characteristics and services provided: United States, 2007.
AB  - OBJECTIVE: This report presents national estimates of the organizational
      characteristics of home health and hospice care agencies in 2007. Comparisons of
      organizational characteristics and provision of selected services are made by
      agency type. A comparison of selected characteristics between 1996 and 2007 is
      also provided to highlight changes that have occurred leading to the current
      composition of the home health and hospice care sector. METHODS: Estimates are
      based on data collected on agencies from the 1996, 2000, and 2007 National Home
      and Hospice Care Survey, conducted by the Centers for Disease Control and
      Prevention's National Center for Health Statistics. Estimates are derived from
      data collected during interviews with administrators and staff designated by the
      administrators. RESULTS: In 2007, there were 14,500 home health and hospice care
      agencies in the United States, an increase from 11,400 in 2000. Three-quarters of
      these agencies provided home health care only, 15% provided hospice care only,
      and 10% provided both home health and hospice care (mixed). The percentage of
      proprietary home health care only and hospice care only agencies increased during
      1996-2007, whereas the percentage of proprietary mixed agencies remained
      relatively stable. The average number of home health care patients that home
      health care only and mixed agencies served decreased, while the average number of
      hospice care patients that hospice care only agencies served increased across
      years. Among mixed agencies, no significant changes were observed in the average
      number of hospice care patients being served. The percentage of home health care
      only agencies offering certain therapeutic and nonmedical services declined over
      the years. There was an increase in the proportion of hospice care only agencies'
      providing many core and noncore hospice care services during 1996-2007. Also
      during this time, the proportion of mixed agencies providing selected nonmedical
      services decreased.

PMID- 21090512
TI  - Security and psychiatry: the British experience and implications for forensic
      psychiatry services in Israel.
AB  - The courts have recently become increasingly involved in the administration of
      compulsory psychiatric services in Israel. Data reveal a gradual increase in the
      rate of court-ordered hospitalizations according to Section 15 of the Law for the
      Treatment of the Mentally Ill. This paper examines the implications of this
      trend, particularly the issues of security and safety in psychiatric
      hospitalization. We present highlights from extensive British experience,
      focusing on the implications on forensic psychiatry in Israel. We review the
      development of the hierarchy of security in the British psychiatric services,
      beginning in the early 1970s with the establishment of the Butler Committee that
      determined a hierarchy of three levels of security for the treatment of patients,
      culminating with the establishment of principles for the operation of medium
      security units in Britain (Read Committee, 1991). These developments were the
      basis for the forensic psychiatric services in Britain. We discuss the relevance
      of the British experience to the situation in Israel while examining the current
      status of mental health facilities in Israel. In our opinion, a safe and suitable
      environment is a necessary condition for a treatment setting. The establishment
      of medium security units or forensic psychiatry departments within a mental
      health facility will enable the concentration and classification of court-ordered
      admissions and will enable systemic flexibility and capacity for better
      treatment, commensurate with patient needs.

PMID- 21090513
TI  - Transradial percutaneous coronary intervention without on-site cardiac surgery
      for stable coronary disease and myocardial infarction: preliminary report and
      initial experience in 174 patients.
AB  - BACKGROUND: On-site cardiac surgery is not widely available in developing
      countries despite a high prevalence of coronary artery disease. OBJECTIVES: To
      analyze the safety, feasibility and cost-effectiveness of transradial
      percutaneous coronary intervention without on-site cardiac surgery in a community
      hospital in a developing country. METHODS: Of the 174 patients who underwent PCI
      for the first time in our center, we analyzed two groups: stable coronary disease
      and acute myocardial infarction. The primary endpoint was the rate of
      complications during the first 24 hours after PCI. We also analyzed the length of
      hospital stay and the rate of hospital readmission in the first week after PCI,
      and compared costs between the radial and femoral approaches. RESULTS: The study
      group comprised 131 patients with stable coronary disease and 43 with acute MI.
      Among the patients with stable coronary disease 8 (6.1%) had pulse loss, 12
      (9.16%) had on-site hematoma, and 3 (2.29%) had bleeding at the site of the
      puncture. Among the patients with acute MI, 3 (6.98) had pulse loss and 5
      (11.63%) had bleeding at the site of the puncture. There were no cases of
      atriovenous fistula or nerve damage. In the stable coronary disease group, 130
      patients (99%) were discharged on the same day (2.4 +/- 2 hours). In the acute MI
      group, the length of stay was 6.6 +/- 2.5 days with at least 24 hours in the
      intensive care unit. There were no hospital readmissions in the first week after
      the procedure. The total cost, which includes equipment related to the specific
      approach and recovery room stay, was significantly lower with the radial approach
      compared to the femoral approach (US$ 500 saving per intervention). CONCLUSIONS:
      The transradial approach was safe and feasible in a community hospital in a
      developing country without on-site cardiac surgery backup. The radial artery
      approach is clearly more cost-effective than the femoral approach.

PMID- 21090514
TI  - Child abuse and neglect: reporting by health professionals and their need for
      training.
AB  - BACKGROUND: For health professionals who interact professionally with children,
      adequate awareness and training regarding the clinical indicators of child abuse
      and neglect, as well as subsequent reporting and procedures, are essential.
      OBJECTIVES: To study Israeli health professionals experiences with identification
      and reporting of suspected cases of child abuse and neglect, and their perceived
      training needs in this area. METHODS: The study group was a convenience sample
      comprising 95 Israeli health professionals (physicians, nurses, social workers,
      psychologists, etc.) attending workshops on medical aspects at a national
      conference on child abuse and neglect. In this cross-sectional survey, the health
      professionals were asked to complete an anonymous structured questionnaire on
      their experience with child abuse and neglect and on their training needs.
      RESULTS: The participants in the survey had relatively high levels of involvement
      with child protection. Nevertheless, they strongly expressed their need for
      training, especially in mastering practice skills. The need for training was
      greater for professionals with less experience in child protection, and there
      were different needs according to profession. CONCLUSIONS: Despite their prior
      extensive experience in dealing with child abuse and neglect, most of the health
      professionals participating in the conference reported the need for training in
      certain areas.

PMID- 21090515
TI  - Validity of self-reported weight and height among 13-14 year old schoolchildren
      in Israel.
AB  - BACKGROUND: Data regarding the validity of self-reported weight and height in
      adolescents are conflicting. OBJECTIVES: To evaluate the validity of self
      reported weight and height among 13-14 year olslddren. METHODS: We conducted a
      cross-sectional study of 517 schoolchildren aged 13-14 years and compared self
      reported and measured weight and height by gender, population group, parental
      education and crowdedness. RESULTS: Females under-reported their weight on
      average by 0.79 +/- 5.46 kg (P = 0.03), resulting in underestimation of the body
      mass index with borderline significance (mean difference 0.28 +/- 2.26 kg/m2, P =
      0.06). Males over-reported their height on average by 0.75 +/- 5.81 cm (P =
      0.03). Children from less crowded homes (< or = 1 person per room) overestimated
      their height more than children from more crowded homes, resulting in a
      significant underestimation of BMI (mean difference between reported BMI and
      measured values was 0.30 +/- 2.36 kg/m2, P = 0.04). Measured BMI was a
      significant predictor of the difference between self-reported and measured BMI,
      adjusted for gender, population group, parents' education, and crowdedness (beta
      = -0.3, P < 0.0001). As a result of this reporting bias, only 54.9% of children
      with overweight and obesity (BMI > or = 85th percentile) were classified
      correctly, while 6.3% of children were wrongly classified as overweight and
      obese. The largest difference in BMI was observed in obese females (4.40 +/-
      4.34) followed by overweight females (218 +/- 1.95) and underweight females (
      1.38 +/- 13.75). Similar findings were observed for males, where the largest
      difference was found among obese males (2.83 +/- 3.44). CONCLUSIONS: Studies
      based on self-reported weight and height in adolescents may be biased. Attempts
      should be made to correct this bias, based on the available data for each
      population.

PMID- 21090516
TI  - The effect of parity and gravidity on the outcome of medical termination of
      pregnancy.
AB  - BACKGROUND: Previous pregnancies may influence the success of medical termination
      of pregnancy. OBJECTIVES: To determine the effect of parity and gravidity on the
      successful termination of pregnancy using mifepristone and misoprostol. METHODS:
      The medical files of all patients attending a department of obstetrics and
      gynecology during the years 2006 and 2007 for the purpose of medical termination
      of pregnancy at < or = 49 days of gestation were analyze retrospectively. The
      medical history, previous pregnancies and deliveries were recorded. Mifepristone
      was administered orally followed by 400 mg of misoprostol 48 hours later. A
      second dose of misoprostol was offered 2 weeks later if uterine content thickness
      was more than 15 mm. Then, after 24 hours, if uterine content thickness was more
      than 15 mm the uterus was evacuated by dilation and curettage. RESULTS: Of 403
      women, 349 (86.6%) aborted following the basic regime; 207 (51.4%) (group A) were
      primiparous while 196 (48.6%) (group B) had at least one prior pregnancy. Uterine
      curettage was performed in 17 patients (8.2%) in group A and in 37 (18.9%) in
      group B (P = 0.002). When patients with a history of a previous abortion were
      excluded from group B, 32 of 143 (22.4%) required curettage (P < 0.001). When
      patients without a history of previous cesarean section were excluded, 10 of 52
      (19.2%) underwent curettage (P = 0.038). CONCLUSIONS: Previous pregnancies
      negatively affect the success of medical termination of pregnancy, especially in
      women with a previous term pregnancy. This information is important when
      counseling women about the method of pregnancy termination.

PMID- 21090517
TI  - Achilles tendon rupture and our experience with the Achillon device.
AB  - BACKGROUND: Open repair of the Achilles tendon is still the gold standard for
      treating rupture. This technique has the disadvantages of a long and problematic
      operative scar and thickly scarred Achilles tendon. To improve the surgical
      outcome minimally invasive techniques have been developed. OBJECTIVES: To analyze
      our results of Achilles tendon repair using the Achillon device and compare them
      with published studies. METHODS: We performed surgical repair of the Achilles
      tendon in 28 patients during a 4 year period (2004-2008): 14 patients were
      treated with the Achillon device, 12 with the open suture technique and 2 with
      the percutaneous method. Fourteen patients were available for follow-up: 9
      patients with the Achillon device, 3 patients with open suturing and 2 patients
      with the percutaneous technique. Follow-up ranged from 1 to 4 years. RESULTS: The
      average score of the AOFAS Ankle-Hindfoot Scale for the group treated with the
      Achillon device was 95.6 points (range 84-100) and for the group treated with the
      open method, 90 points (range 84-98). The length of the scar in patients operated
      with a minimally invasive technique was 3.81 cm (range 1-6 cm) as compared to
      9.16 cm (range 8-10.5 cm) with the open suture. CONCLUSIONS: This is the first
      review on this procedure in Israel. Excellent functional results were achieved
      with this technique. Our outcomes were similar to those of two other studies.

PMID- 21090518
TI  - Short and long-term outcome of pregnant women with preexisting dilated
      cardiomypathy: an NTproBNP and echocardiography-guided study.
AB  - BACKGROUND: Little is known of the outcome of pregnant patients with previously
      diagnosed dilated cardiomyopathy. These patients are usually firmly advised
      against continuation of the pregnancy. OBJECTIVES: To examine the usefulness of
      serial echocardiographic follow-up and plasma N-terminal pro-B type natriuretic
      peptide levels in the management of pregnant women with preexisting DCM. METHODS:
      We prospectively enrolled pregnant women with DCM either known or diagnosed in
      the first trimester. Clinical examination and serial echocardiography studies
      were performed at baseline, at 30 weeks gestation, peripartum, and 3 and 18
      months postpartum. Blinded NTproBNP levels were obtained at 30 weeks, at delivery
      and 3 months postpartum. RESULTS: Between June 2005 and October 2006 we enrolled
      seven women who fulfilled the study criteria. Delivery and postpartum were
      complicated in 3 patients (42%): 2 with acute heart failure, which resolved
      conservatively, and 1 with major pulmonary embolism. The left ventricular
      ejection fraction was stable throughout the pregnancy (35% +/- 2.8 at baseline,
      33% +/- 2.9 at 30 weeks) and postpartum (35% +/- 2.8 at 1 day, 34% +/- 3.1 at 90
      days). Similar stable behavior was observed regarding left ventricular
      dimensions: LV end-systolic diameters 43.3 +/- 2.7 mm and LV end-diastolic
      diameters 57.3 +/- 3.3 mm at baseline compared with 44.1 +/- 3.1 mm and 58.7 +/-
      3.1 mm postpartum, respectively. The NTproBNP levels rose significantly
      peripartum in all three patients with complications. CONCLUSIONS: Serial NTproBNP
      levels, as compared to echocardiography, may be a better clinical tool in
      monitoring and management of pregnant women with preexisting DCM. An early rise
      in NTproBNP level appears to predict the occurrence of adverse events.

PMID- 21090519
TI  - Kikuchi-Fujimoto disease.
AB  - BACKGROUND: Kikuchi-Fujimoto disease is a benign and self-limited disease, first
      reported in Japan in 1972. The characteristic features of this disorder include
      lymphadenopathy and fever. OBJECTIVES: To summarize our experience with Kikuchi
      disease with regard to clinical manifestations and outcome. METHODS: The patients
      included in the study were those diagnosed with Kikuchi disease during the years
      2005-2008 in two departments of internal medicine at Sheba Medical Center.
      RESULTS: We identified five patients with Kikuchi disease; four were women and
      the mean age was 22.6 years. All the patients had cervical lymphadenopathy; three
      had other sites of lymphadenopathy. Four of the patients had fever higher than 39
      degrees C. Two of them had splenomegaly and three reported weight loss. Three of
      the five patients experienced a relapse of the disease and were treated with
      steroids or non-steroidal anti-inflammatory agents. The diagnosis was confirmed
      in all the patients by an excisional biopsy of lymph node. CONCLUSIONS: Kikuchi
      disease must be considered in every young patient with fever and lymphadenopathy.
      The disease usually has a benign course.

PMID- 21090520
TI  - Predictors of pandemic (H1N1) 2009 virus positivity and adverse outcomes among
      hospitalized patients with a compatible syndrome.
AB  - BACKGROUND: A pandemic (H1N1) influenza A virus was identified in 2009.
      OBJECTIVES: To investigate predictors for pandemic (H1N1) 2009 virus infection
      among hospitalized patients with a flu-like illness and to identify parameters
      suggesting a severe clinical course. METHODS: We analyzed a cohort of all
      patients hospitalized during a 2 month period with a flu-like syndrome who were
      tested for pandemic (H1N1) 2009 infection. Demographic, clinical and laboratory,
      along with outcome parameters, were recorded and compared between pandemic (H1N1)
      2009 virus-positive and negative hospitalized patients. RESULTS: Of the 179
      examined hospitalized patients suspected of having pandemic (H1N1) 2009 infection
      65 (36%) were found positive. These patients tended to be younger and had
      significantly fewer comorbidities. In addition, they had a significantly higher
      frequency of fever (94%), cough (86%) and myalgia (29%). Furthermore, age 65
      years and cough were independent predictors for pandemic (H1N1) 2009 virus
      positivity in a multivariate regression analysis. Notably, 14 of the 65 positive
      patients (21.5%) had acute respiratory insufficiency requiring treatment in the
      intensive care unit. These patients were neither older nor previously sicker than
      patients with non-severe disease, but were distinguished by augmented
      inflammatory markers, significant lymphopenia associated with disease severity,
      and overall mortality of 21.4%. CONCLUSIONS: Pandemic (H1N1) 2009 virus-positive
      hospitalized patients tend to be younger and have fewer comorbidities as compared
      to compatible negative patients. A significant number of relatively young and
      previously healthy positive patients might develop severe disease associated with
      a robust inflammatory reaction and significant lymphopenia.

PMID- 21090521
TI  - Novel multitargeted anticancer oral therapies: sunitinib and sorafenib as a
      paradigm.
AB  - The introduction of novel targeted therapies into the clinic in recent years has
      had a considerable impact on the management of several neoplastic diseases--such
      as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell
      carcinomas--considered until recently refractory to systemic therapies. We
      describe here two such novel biological agents, sunitinib and sorafenib, as a
      paradigm of the successful clinical application of new concepts. Sunitinib and
      sorafenib are small molecule tyrosine kinase inhibitors that target vascular
      endothelial growth factor receptor, platelet-derived growth factor receptor, C
      Kit and others. Both agents are administered orally; sunitinib is tyically given
      in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given
      continually. Side effects occur in most patients, similar for both agents; they
      may affect several systems and organs but are mostly mild and easily manageable,
      rarely requiring discontinuation of the drug. However, these toxicities mandate
      prompt attention and intervention. The most frequently observed effects are
      hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac
      abnormalities may include congestive failure. Sunitinib, and markedly less
      frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism.
      Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for
      sunitinib as first-line treatment and for sorafenib in previously treated
      patients as second-line. Sunitinib is now approved as second-line therapy for
      patients with GIST refractory to imatinib; sorafenib has resulted in a
      significant prolongation in median survival in patients with hepatocellular
      carcinoma. Ongoing clinical trials will further define the spectrum of these
      agents' antitumor activity, their role in combination with other drugs, as well
      as their optimal dose and schedule of administration.

PMID- 21090522
TI  - The proper place for the committer of a crime is prison custody not psychiatric
      hospital inpatient care.

PMID- 21090523
TI  - Infections more than vaccines are inducers of autoimmune diseases.

PMID- 21090524
TI  - Antiphospholipid syndrome following a diphtheria-tetanus vaccination: coincidence
      vs. causality.

PMID- 21090525
TI  - Acute pancreatitis may be caused by H1N1 influenza A virus infection.

PMID- 21090526
TI  - Colon and lung choriocarcinoma.

PMID- 21090527
TI  - Lessons from the history of hormone replacement therapy.

PMID- 21090528
TI  - Therapeutic potential of herbal drugs in cerebral ischemia.
AB  - Stroke is one of the most important causes of mortality and morbidity in the
      world. Prevention and effective treatment of stroke is of the utmost importance.
      Cerebral ischemia causes disturbances in a variety of cellular and molecular
      mechanisms, including oxidative phosphorylation, membrane function,
      neurotransmitter release, and free radical generation. It has been years since
      tissue-type plasminogen activator (t-PA) became the first medication approved by
      the FDA for the management of stroke, with limited success. Thrombolytic therapy
      is the most effective therapeutic strategy for the prevention of brain injury and
      reduction of mortality in patients with cerebral infarction. However, a
      combination of established thrombolytic therapy and effective neuronal protection
      therapy may have more beneficial effects for patients with cerebral infarction.
      Because clinical trials of pharmacological neuroprotective strategies in stroke
      have been disappointing, attention has turned towards approaches which include
      herbal drugs that can be used in limiting the neurological damage associated with
      stroke. Herbal drugs may be used as prophylactic treatment in patients with high
      risk of stroke. Herbals drugs have been described in ancient systems of medicine
      for the treatment of various ailments associated with stroke and have more
      recently been reported to be beneficial in treating stroke. However, the strength
      of evidence to support the use of these herbal drugs is unclear. This review
      focuses on putative mechanisms underlying the beneficial effects of herbal drugs
      in patients with stroke and on the possibility of herbal drugs to increase the
      therapeutic time window in patients with cerebral ischemia.

PMID- 21090529
TI  - Prediction and stratification of the future cardiovascular arrhythmic events:
      signal averaged electrocardiography versus ejection fraction.
AB  - Cardiac arrhythmias as cause of sudden cardiac death remains an important public
      health problem. The availability of effective treatment in terms of the
      implantable defibrillator makes it critical to identify individuals at risk. An
      essential step in this process is the use of noninvasive techniques to screen
      patients and identify those at risk. The detection of ventricular late potential
      using the SAECG as a non-invasive technique is being explored for this purpose.
      The objective of the study was to stratify the future cardiovascular events
      including life threatening cardiac arrhythmias, in different cardiac diseases
      through positive and negative predictive values of SAECG and comparing with EF%
      another mechanical determinant. The study was conducted on 152 subjects selected
      from the OPD and admitted case of the New Civil Hospital and Govt. Medical
      College, Surat; between 25 to 75 years of age group, from August 2001 to June
      2004. 80 healthy subjects free from any major acute/chronic illness were selected
      as a control using our own normative values for SAECG. The statistical analysis
      was performed using SPSS package. The results obtained were analyzed for
      significance by using Chi square and Independent 't' test. When we compared the
      cardiac arrhythmic events on 6 month follow-up study, based on SAECG and EF%
      separately we found that negative predictive value of SAECG was more (99.1%) than
      negative predictive value of EF% (93.6%). However positive predictive values for
      cardiac arrhythmic events of SAECG were less (28.9%) compare to EF% (42.9%). When
      both the parameters SAECG and EF% are considered together the negative as well as
      positive predictive values of these tests were quite high (100% and 50%
      respectively). In this study conducted on 152 patients we found that SAECG and
      EF% together were an accurate predictor of the cardiac arrhythmic events in terms
      of positive and negative predictive value while SAECG or EF% alone were not.
      However SAECG has got a more negative predictive value compare to EF%. In this
      study SAECG compared favorably or even better than EF% for risk stratification.
      SAECG and EF% together (and not separately) may be considered as a better
      investigational tool to stratify future cardiovascular arrhythmic events.

PMID- 21090530
TI  - Immunomodulatory activity of methanolic leaf extract of Moringa oleifera in
      animals.
AB  - AIM: The aim of the present study was to investigate the immunomodulatory action
      of methanolic extract of Moringa oleifera (MEMO) in an experimental model of
      immunity. The cellular immunity was evaluated using neutrophil adhesion test,
      cyclophosphamide induced neutropenia and carbon clearance assay, whereas, humoral
      immunity was tested by mice lethality test, serum immunoglobulin estimation and
      indirect haemagglutination assay in animals. Administration of MEMO (250 and 750
      mg/kg, po) and Ocimum sanctum (100 mg/kg, po) significantly increased the levels
      of serum immunoglobulins and also prevented the mortality induced by bovine
      Pasteurella multocida in mice. They also increased significantly the circulating
      antibody titre in indirect haemagglunation test. Moreover, MEMO produced
      significant increase in adhesion of neutrophils, attenuation of cyclophosphamide
      induced neutropenia and an increase in phagocytic index in carbon clearance
      assay. From the above results, it can be concluded that MEMO stimulate both
      cellular and humoral immune response. However, low dose of MEMO was found to be
      more effective than the high dose.

PMID- 21090531
TI  - Modulatory effect of coffee on platelet function.
AB  - Blood platelets play a major role in cardiovascular disease (CVD) and thrombosis.
      Conflicting information exists regarding the effect of coffee consumption on the
      cardiovascular system. We have investigated whether the consumption of moderate
      amount of coffee affect platelet functions and primary hemostasis in vivo in
      normal and high fat diet fed rats. Coffee fed group showed significant (P < 0.05)
      decrease in mean platelet volume, platelet crit and platelet distribution width
      as compared to high fat diet (HFD) group. The concentration of malondialdehyde in
      platelets increased in atherosclerotic group indicates the increased thromboxane
      A2 (TXA2) production from membrane arachidonic acid and it was decreased in
      coffee treated group. Platelet aggregation studies with ADP, collagen,
      arachidonic acid and epinephrine showed significant (P < 0.05) decrease in
      aggregation in coffee fed group. Scanning electron microscopic studies revealed
      that platelet aggregation tendency increased in HFD group and was reduced in
      coffee fed group. These results indicate that coffee is active in inhibiting
      platelet aggregation, a critical step involved in thrombosis.

PMID- 21090532
TI  - Impact of different grades of body mass index on left ventricular structure and
      function.
AB  - Overweight and obesity influences left ventricular structure and function. WHO
      Western Pacific Region in 2000 recommended lower cutoff for overweight (Body Mass
      Index-BMI > or = 23.0) and obesity (Body Mass Index-BMI > or = 25.0) in Asians.
      However, studies considering the new recommendations of body mass index (BMI) are
      lacking. The present study investigated the impact of different grades of BMI on
      left ventricular structure and systolic and diastolic function in middle aged
      Indian men. The study involved 74 men aged 31 to 60 (mean age 45.24 +/- 10.9)
      years who were grouped according to BMI as normal weight (18.5-22.9 kg/m2, n=19),
      overweight (23-24.9 kg/m2, n=17) and obese (> or =25 kg/m2, n=38). Left
      ventricular structure and function were evaluated by 2-D doppler
      echocardiography. Compared to normal and overweight, obese had significantly
      higher left ventricular mass (P < 0.05) and left atrial diameter (P < 0.01). Left
      ventricular diastolic function (atrial filling velocity-A) showed a significant
      decline in obese and even in overweight compared to normal (P < 0.05). Left
      ventricular systolic function showed no significant changes with increase in BMI.
      Left ventricular diastolic function decreases in all grades of BMI more than 23
      kg/m2, whereas structural changes are present only in obese (BMI > or =25 kg/m2).
      Hence the revised BMI cut-off for Asians as recommended by WHO need to be
      considered for assessing cardiovascular risk and mortality among Indian men and
      more stringent control of body weight especially abdominal obesity is justified
      in the maintenance of cardiovascular health and functional capacity.

PMID- 21090533
TI  - Multivitamin and micronutrient treatment improves semen parameters of azoospermic
      patients with maturation arrest.
AB  - The study was undertaken to evaluate the efficacy of multivitamin and
      micronutrient supplementation in azoospermic patients with maturation arrest. A
      total of 35 azoospermic patients showing maturation arrest on testicular biopsy
      were recruited in this study. The patients were divided into two groups.
      Untreated group (n=11) without any treatment and treated group (n=24) who
      received multivitamins, micronutrients and co-enzyme Q10. The sperm
      concentration, motility and morphology were evaluated at monthly interval. The
      results showed reduction in liquefaction time and relative viscosity of the semen
      in the treated group. Further, in treated group there was appearance of
      spermatozoa (4.0 million/ml) exhibiting progressive motility (7%) and normal
      morphology (6%), even in the first follow up visit. The sperm count, motility and
      normal morphology increased significantly on subsequent visits. Within 3 months
      (3 visits) 2 pregnancies were reported. These observations indicate that
      multivitamin and micronutrient supplementation improve the qualitative and
      quantitative parameters of seminogram in patients with azoospermia of maturation
      arrest.

PMID- 21090534
TI  - Effect of Valsalva maneuver on pulse wave velocity.
AB  - Pulse wave velocity (PWV) was recorded in different arterial segments in 25 male
      normal healthy individuals, before, during and after Valsalva maneuver (VM).
      Heart rate (HR) and blood pressure (BP) showed significantly significant (P <
      0.001) variation in phase II and IV of VM compared to baseline. PWV in aorta to
      femoral (AO-Fem) arterial segment revealed progressive increase from baseline to
      phase IV of VM (P < 0.001), while PWV in femoral to dorsalis pedis (Fem-DP)
      arterial segment showed more increase (P < 0.001) in phase II rather than phase
      IV from baseline with insignificant variation in aorta to radial (AO-Rad)
      arterial segment, demonstrate different response of arterial segments to VM.

PMID- 21090535
TI  - Impaired glucose tolerance: a pilot study in randomly selected population of
      Chennai.
AB  - Impaired glucose tolerance (IGT) is considered as a prediabetic state that
      occupies a grey area between diabetes mellitus (DM) and normal glucose tolerance
      (NGT). If diabetes is detected at the stage of impaired glucose tolerance, it may
      be possible to halt the progression to overt diabetes. The study was conducted to
      assess the prevalence of impaired glucose tolerance and its relation with age,
      sex, body mass index (BMI), waist-hip ratio (WHR) and family history of diabetes
      mellitus in a randomly selected Chennai population of 200 subjects of both sexes
      as per the inclusion and exclusion criteria. Blood glucose concentration, body
      mass index and waist-hip ratio were measured by approved methods. All the data
      were statistically analyzed. Prevalence of IGT in this study population is 8.5%.
      BMI and family history of diabetes showed association with IGT. WHR showed
      association with IGT in males, but not in females. The prevalence of IGT is
      similar with differing age groups and sex.

PMID- 21090536
TI  - Influence of age and gender on cold pressor response in Indian population.
AB  - Cold pressor test (CPT) is a simple and well documented laboratory test to
      evaluate the propensity for hypertension and sympathetic autonomic functions.
      Role of sex hormones was tested in the present study for the cold pressor
      response (CPR) in young adults of both sexes and in elderly population. The
      subjects comprised of young male (n=55), female (n=32) medical students of 17-25
      years and elderly males (n=39) and females (n=25) of 50-70 years of age. The CPT
      was carried out in young and elderly males and females with one minute immersion
      of one hand in ice cold water (0-4 degrees C). Both in young males and females
      the absolute rise in SBP and DBP in response to Cold pressor test (CPT) was
      highly significant, with diastolic percent rise exceeding systolic. In comparison
      to young males, the females showed greater percent rise in SBP and DBP.
      Similarly, in elderly groups of both sexes, CPR was associated with significant
      absolute rise in SBP and DBP with diastolic percent rise more than systolic in
      males only. Both in young versus elderly males and young versus elderly females
      comparison yielded comparable percent rise in SBP and DBP. The SBP and DBP
      percent rise was again comparable between elderly males and females. The greater
      responsiveness to CPT in young females could be attributed to increased pain
      sensitivity to cold, and/or genetic and hereditary factors overwhelming the
      hormonal protection offered by estrogen and nitric oxide (NO).

PMID- 21090537
TI  - Myocardial infarction in prediabetic patients: role of blood pressure
      dyshomeostasis.
AB  - Male gender and fasting sugar level at pre diabetic range are two of the
      recognized risk factors associated with coronary artery disease. Recently it was
      found that although males are at increased incidence of myocardial infarction
      (MI), the severity of disease is same for both genders among pre-diabetic
      myocardial infarction cases. In this study, we have retrospectively analyzed
      various biochemical and physiological parameters and cardiac markers of patients
      admitted for the first instance of myocardial infarction. We found an evidence of
      impairment in blood pressure homeostasis in female patients which could be one of
      the factors responsible for the equal degree of severity in myocardial infarction
      among females compared to males, despite lower incidence of MI in them.

PMID- 21090538
TI  - Effect of yoga and relaxation techniques on cardiovascular system.

PMID- 21090539
TI  - Responses to the comments made by David S. Shannahoff-Khalsa [IJPP 2009; 53(1):
      102-104] on the short communication "Immediate effects of right and left nostril
      breathing on verbal and spatial memory scores" [IJPP 2008; 52: 197-200]

PMID- 21090540
TI  - Nobel Prize in Chemistry 2009.

PMID- 21090541
TI  - Courts rejected RIL: did nurses botch sponge count? Baxter v. Ash Samaritan
      Hospital, LLC, 2008-CA-000541-MR KYCA (1/15/2010)-KY.

PMID- 21090542
TI  - Failure to administer cefotan: was standing order ambiguous? Tucker v. Women's
      Care Physicians of Louisville, CA-001929-mr(6/18/2010)-KY.

PMID- 21090543
TI  - MN: Did nurses fail to timely call for help?: Court reversed summary judgment for
      hospital. Kuhne v. Allina Health Systems, A-09-1826 MNCA(6/15/2010)-MN.

PMID- 21090544
TI  - Evidence of re-education of nurse held inadmissible. Alfieri v. Carmelite Nursing
      Home, Inc., 210-20316 NYMisc (8/10/2010)-NY.

PMID- 21090545
TI  - Multipollutant air quality management.

PMID- 21090546
TI  - Directions for combustion engine aerosol measurement in the 21st century.
AB  - The Coordinating Research Council convened two Real-Time PM Measurement Workshops
      in December 2008 and March 2009 to take an intensive look at the current status
      and future directions of combustion aerosol measurement. The purpose was to
      examine the implications of parallel rapid developments over the past decade in
      ambient aerosol science, engine aftertreatment technology, and aerosol
      measurement methodology, which provide benefits and challenges to the
      stakeholders in air quality management. The workshops were organized into
      sessions targeting key issues in ambient and source combustion particulate matter
      (PM). These include (1) metrics to characterize and quantify PM, (2) the need to
      reconcile ambient and source measurements, (3) the role of atmospheric
      transformations on modeling emissions and exposures, (4) the impact of sampling
      conditions on PM measurement, and (5) the potential benefits of novel PM
      instrumentation. This paper distills the material presented by subject experts
      and the insights derived from the in-depth discussions that formed the core of
      each session. The paper's objectives are to identify areas of consensus that
      allow wider practical application of the past decade's advances in combustion
      aerosol measurement to improve emissions and air quality modeling, develop
      emissions reduction strategies, and to recommend directions for progress on
      issues in which uncertainties remain.

PMID- 21090547
TI  - Alternatives to the gravimetric method for quantification of diesel particulate
      matter near the lower level of detection.
AB  - This paper is part of the Journal of the Air & Waste Management Association's
      2010 special issue on combustion aerosol measurements. The issue is a combination
      of papers that synthesize and evaluate ideas and perspectives that were presented
      by experts at a series of workshops sponsored by the Coordinating Research
      Council that aimed to evaluate the current and future status of diesel
      particulate matter (DPM) measurement. Measurement of DPM is a complex issue with
      many stakeholders, including air quality management and enforcement agencies,
      engine manufacturers, health experts, and climatologists. Adoption of the U.S.
      Environmental Protection Agency 2007 heavy-duty engine DPM standards posed a
      unique challenge to engine manufacturers. The new standards reduced DPM emissions
      to the point that improvements to the gravimetric method were required to
      increase the accuracy and the sensitivity of the measurement. Despite these
      improvements, the method still has shortcomings. The objectives of this paper are
      to review the physical and chemical properties of DPM that make gravimetric
      measurement difficult at very low concentrations and to review alternative
      metrics and methods that are potentially more accurate, sensitive, and specific.
      Particle volatility, size, surface area, and number metrics are considered, as
      well as methods to quantify them. Although the authors believe that an
      alternative method is required to meet the needs of engine manufacturers, the
      methods reviewed in the paper are applicable to other areas where the gravimetric
      method detection limit is approached and greater accuracy and sensitivity are
      required. The paper concludes by suggesting a method to measure active surface
      area, combined with a method to separate semi-volatile and solid fractions to
      further increase the specificity of the measurement, has potential for reducing
      the lower detection limit of DPM and enabling engine manufacturers to reduce DPM
      emissions in the future.

PMID- 21090548
TI  - Evolution of vehicle exhaust particles in the atmosphere.
AB  - Aerosol mass spectrometer (AMS) measurements are used to characterize the
      evolution of exhaust particulate matter (PM) properties near and downwind of
      vehicle sources. The AMS provides time-resolved chemically speciated mass
      loadings and mass-weighted size distributions of nonrefractory PM smaller than 1
      microm (NRPM1). Source measurements of aircraft PM show that black carbon
      particles inhibit nucleation by serving as condensation sinks for the volatile
      and semi-volatile exhaust gases. Real-world source measurements of ground vehicle
      PM are obtained by deploying an AMS aboard a mobile laboratory. Characteristic
      features of the exhaust PM chemical composition and size distribution are
      discussed. PM mass and number concentrations are used with above-background gas
      phase carbon dioxide (CO2) concentrations to calculate on-road emission factors
      for individual vehicles. Highly variable ratios between particle number and mass
      concentrations are observed for individual vehicles. NRPM1 mass emission factors
      measured for on-road diesel vehicles are approximately 50% lower than those from
      dynamometer studies. Factor analysis of AMS data (FA-AMS) is applied for the
      first time to map variations in exhaust PM mass downwind of a highway. In this
      study, above-background vehicle PM concentrations are highest close to the
      highway and decrease by a factor of 2 by 200 m away from the highway. Comparison
      with the gas-phase CO2 concentrations indicates that these vehicle PM mass
      gradients are largely driven by dilution. Secondary aerosol species do not show a
      similar gradient in absolute mass concentrations; thus, their relative
      contribution to total ambient PM mass concentrations increases as a function of
      distance from the highway. FA-AMS of single particle and ensemble data at an
      urban receptor site shows that condensation of these secondary aerosol species
      onto vehicle exhaust particles results in spatial and temporal evolution of the
      size and composition of vehicle exhaust PM on urban and regional scales.

PMID- 21090549
TI  - Updating the conceptual model for fine particle mass emissions from combustion
      systems.
AB  - Atmospheric transformations determine the contribution of emissions from
      combustion systems to fine particulate matter (PM) mass. For example, combustion
      systems emit vapors that condense onto existing particles or form new particles
      as the emissions are cooled and diluted. Upon entering the atmosphere, emissions
      are exposed to atmospheric oxidants and sunlight, which causes them to evolve
      chemically and physically, generating secondary PM. This review discusses these
      transformations, focusing on organic PM. Organic PM emissions are semi-volatile
      at atmospheric conditions and thus their partitioning varies continuously with
      changing temperature and concentration. Because organics contribute a large
      portion of the PM mass emitted by most combustion sources, these emissions cannot
      be represented using a traditional, static emission factor. Instead, knowledge of
      the volatility distribution of emissions is required to explicitly account for
      changes in gas-particle partitioning. This requires updating how PM emissions
      from combustion systems are measured and simulated from combustion systems.
      Secondary PM production often greatly exceeds the direct or primary PM emissions;
      therefore, secondary PM must be included in any assessment of the contribution of
      combustion systems to ambient PM concentrations. Low-volatility organic vapors
      emitted by combustion systems appear to be very important secondary PM precursors
      that are poorly accounted for in inventories and models. The review concludes by
      discussing the implications that the dynamic nature of these PM emissions have on
      source testing for emission inventory development and regulatory purposes. This
      discussion highlights important linkages between primary and secondary PM, which
      could lead to simplified certification test procedures while capturing the
      emission components that contribute most to atmospheric PM mass.

PMID- 21090550
TI  - The potential of a partial-flow constant dilution ratio sampling system as a
      candidate for vehicle exhaust aerosol measurements.
AB  - This paper presents the measurement of airborne particle properties with use of a
      dedicated sampling protocol and a measurement setup directly installed in the
      exhaust line of vehicles and engines. The sampling system dilutes a small part of
      the exhaust directly at the tailpipe without the need of exhaust gas transfer
      lines that may lead to sampling artifacts. Dilution takes place in two steps with
      a primary dilution ratio universally set at a value of 12.5:1 for all vehicles
      and engines tested, and subsequent dilution steps reducing particle concentration
      within the measuring range of the instruments used. Dilution air temperature and
      residence time were set at 32 degrees C and 2.5 sec respectively, to allow
      repeatable measurement of nucleation-mode particles. The paper summarizes the
      specifications of the system, evaluates its performance in comparison to real
      world dilution (chasing experiments), and presents the repeatability and
      reproducibility of measurements performed in different laboratories. In general,
      after taking precautions for the setup and condition of instruments, both
      measurement quality indices reached levels similar to the measurement of
      particulate matter (PM) mass. Application of the system, using the same protocol,
      to measure many light-duty vehicles and engines is finally demonstrated,
      providing useful conclusions for the emission performance of different sized
      engines. The study concludes that the use of partial-flow sampling systems may
      offer advantages for the measurement of particle emissions from low-emission
      engines compared with constant volume sampling facilities, including lower cost
      of purchase and operation, versatility, lack of artifacts, and possibilities for
      standardization in different environments.

PMID- 21090551
TI  - Theoretical versus observed gas-particle partitioning of carbonyl emissions from
      motor vehicles.
AB  - A state-of-the-science thermodynamic model describing gas-particle absorption
      processes was used to predict the gas-particle partitioning of mixtures of
      approximately 60 carbonyl compounds emitted from low-emission gasoline-powered
      vehicles, three-way catalyst gasoline-powered vehicles, heavy-duty diesel
      vehicles under the idle-creep condition (HDDV idle), and heavy-duty diesel
      vehicles under the five-mode test (HDDV 5-mode). Exhaust was diluted by a factor
      of 120-580 with a residence time of approximately 43 sec. The predicted
      equilibrium absorption partitioning coefficients differed from the measured
      partitioning coefficients by several orders of magnitude. Time scales to reach
      equilibrium in the dilution sampling system were close to the actual residence
      time during the HDDV 5-mode test and much longer than the actual residence time
      during the other vehicle tests. It appears that insufficient residence time in
      the sampling system cannot uniformly explain the failure of the absorption
      mechanism to explain the measured partitioning. Other gas-particle partitioning
      mechanisms (e.g., heterogeneous reactions, capillary adsorption) beyond the
      simple absorption theory are needed to explain the discrepancy between calculated
      carbonyl partitioning coefficients and observed partitioning. Both of these
      alternative partitioning mechanisms imply great challenges for the measurement
      and modeling of semi-volatile primary organic aerosol (POA) species from motor
      vehicles. Furthermore, as emitted particle concentrations from newer vehicles
      approach atmospheric background levels, dilution sampling systems must
      fundamentally change their approach so that they use realistic particle
      concentrations in the dilution air to approximately represent real-world
      conditions. Samples collected with particle-free dilution air yielding total
      particulate matter concentrations below typical ambient concentrations will not
      provide a realistic picture of partitioning for semi-volatile compounds.

PMID- 21090552
TI  - Can real-world diesel exhaust particle size distribution be reproduced in the
      laboratory? A critical review.
AB  - Real-world particulate emission measurements usually include a fresh nanoparticle
      mode called the nucleation mode. The formation of the nucleation mode during
      mixing, dilution, and cooling of diesel exhaust is discussed based on existing
      experimental and modeling data. The further evolution of the nucleation mode and
      the local dilution ratio within the vehicle exhaust is reviewed. The nucleation
      mode forms at low dilution ratios (< or = 10) and is fully formed at the dilution
      ratio of approximately 100. The findings of the studies comparing real-world and
      dynamometer measurements are reviewed. A qualitative agreement of nucleation mode
      formation is generally observed. The geometric mean diameter of the nucleation
      mode, measured on-road, is well reproduced in the laboratory. However, the number
      concentration of the nucleation mode is too low in the laboratory (by a factor of
      2-10). Nevertheless, the trends are reproduced, including those caused by
      differences in vehicle speed and engine load, engine and aftertreatment
      technology, as well as fuel and lubricant composition.

PMID- 21090553
TI  - Synthesis of chromium-doped malayaite pigments from wastewater containing low
      chromium(VI).
AB  - A malayaite pigment was synthesized with wastewater containing low chromium
      (Cr)(VI) by a novel liquid-phase reaction method. The effects of the particle
      size of the precursor and calcination temperature on the final product are
      examined. The result of scanning electron microscopy shows that the obtained
      precursor is amorphous and the particle size is approximately 250 nm. The results
      of X-ray diffraction and differential scanning calorimetry show that the complete
      transformation temperature was approximately 1050 degrees C. Furthermore, the
      Commission International de l'Eclairage laboratory shows that the red color of as
      prepared pigments is more saturated with a high a* value at 34.1. This process of
      malayaite pigment preparation via reuse of the Cr(VI)-containing wastewater is
      quite simple, economical, and energy-saving for the industry, and the products
      have a saturated red color. There is considerable foreground for the industrial
      application of this work.

PMID- 21090554
TI  - Fugitive dust emission source profiles and assessment of selected control
      strategies for particulate matter at gravel processing sites in Taiwan.
AB  - Particles emitted from gravel processing sites are one contributor to worsening
      air quality in Taiwan. Major pollution sources at gravel processing sites include
      gravel and sand piles, unpaved roads, material crushers, and bare ground. This
      study analyzed fugitive dust emission characteristics at each pollution source
      using several types of particle samplers, including total suspended particulates
      (TSP), suspended particulate (PM10), fine suspended particulate (PM2.5),
      particulate sizer, and dust-fall collectors. Furthermore, silt content and
      moisture in the gravel were measured to develop particulate emission factors. The
      results showed that TSP (< 100 microm) concentrations at the boundary of gravel
      sites ranged from 280 to 1290 microg/m3, which clearly exceeds the Taiwan hourly
      air quality standard of 500 microg/m3. Moreover, PM10 concentrations, ranging
      from 135 to 550 microg/m3, were also above the daily air quality standard of 125
      microg/m3 and approximately 1.2 and 1.5 times the PM2.5 concentrations, ranging
      from 105 to 470 microg/m3. The size distribution analysis reveals that mass mean
      diameter and geometric standard deviation ranged from 3.2 to 5.7 microm and from
      2.82 to 5.51, respectively. In this study, spraying surfactant was the most
      effective control strategy to abate windblown dust from unpaved roads, having a
      control efficiency of approximately 93%, which is significantly higher than using
      paved road strategies with a control efficiency of approximately 45%. For paved
      roads, wet suppression provided the best dust control efficiencies ranging from
      50 to 83%. Re-vegetation of disturbed ground had dust control efficiencies
      ranging from 48 to 64%.

PMID- 21090555
TI  - Natural desulfurization in coal-fired units using Greek lignite.
AB  - This paper analyzes the natural desulfurization process taking place in coal
      fired units using Greek lignite. The dry scrubbing capability of Greek lignite
      appears to be extremely high under special conditions, which can make it possible
      for the units to operate within the legislative limits of sulfur dioxide (SO2)
      emissions. According to this study on several lignite-fired power stations in
      northern Greece, it was found that sulfur oxide emissions depend on coal rank,
      sulfur content, and calorific value. On the other hand, SO2 emission is inversely
      proportional to the parameter gammaCO2(max), which is equal to the maximum carbon
      dioxide (CO2) content by volume of dry flue gas under stoichiometric combustion.
      The desulfurization efficiency is positively correlated to the molar ratio of
      decomposed calcium carbonate to sulfur and negatively correlated to the free
      calcium oxide content of fly ash.

PMID- 21090557
TI  - Therapeutic approach and prevention in recurrent acute biliary pancreatitis.
AB  - OBJECTIVES: Acute biliary pancreatitis (ABP) is caused by alteration of the
      papillary patency. The normal transpapillar flux and the cleaning of the common
      biliary duct (CBD) may prevent potentially avoidable recurrent pancreatitis.
      METHODS: In the period September 1997/December 2008 we have treated 224 ABP (34
      severe, 190 mild/moderate): 162 (72,4%) with the first attack, 62 (27.6%) with
      recurrent ABP (second or further attack). The patients with recurrent
      pancreatitis had not undergone, in the previous hospital stay elsewhere, the
      evaluation and, if necessary, the treatment of the papillary obstacle and/or CBD
      stones, sludge, etc. In our hospital all patients had undergone the treatment of
      ABR The treatment was completed with cholecystectomy. All the patients, after the
      discharge, were introduced in a follow-up program (clinical and ultrasonographic
      (US) control after 180 days and 1 year). RESULTS: In the follow-up of recurrent
      pancreatitis we have controlled 35 patients (56%-27 lost). The results of the
      follow-up showed, beside the absence of recurrent acute episodes, the stable
      normalization of laboratory cholestasis tests and US control. The same controls
      in 78 patients (48.1%) with a first attack of acute pancreatitis resulted normal
      in absence of a new acute episode. CONCLUSIONS: Recurrent ABP have been caused by
      persistent papillary obstacle. Therefore we confirm therapeutic validity of the
      instrumental control (US/MRCP) and the possible treatment of papillary or biliary
      lithiasic obstacle for the prevention of recurrent ABP?

PMID- 21090556
TI  - The prognostic significance of thoracic and abdominal trauma in severe trauma
      patients (Injury severity score > 15).
AB  - The aim of the present study was to assess the prognostic significance of
      thoracic and abdominal trauma in severely injured patients. A retrospective
      analysis was performed based on data from the period from March 1 2006 to
      December 31 2007, taken from the Trauma Registry of the University Hospital
      "SantAndrea" in Rome. A total of 844 trauma patients were entered in a database
      created for this purpose, and only patients with an Injury Severity Score (ISS) >
      15, (163 patients, 19.3%), were selected for the present study. These patients
      were divided into 2 groups: Group A (103 patients, 63.2%), consisting of patients
      with at least one thoracic injury, and Group B (46 patients, 28.2%) consisting of
      patients with concomitant thoracic and abdominal injuries. The impact of thoracic
      and abdominal trauma was studied by analyzing mortality and morbidity, in
      relation to patient age, cause and dynamics of trauma, length of hospital stay,
      and both ISS and New ISS (NISS). In a vast majority of cases, the cause of trauma
      was a road accident (126 patients, 77.3%). The mean age of patients with ISS > 15
      was 45.2 +/- 19.3 years. The mean ISS and NISS were 25.7 +/- 10.5 and of 31.4 +/-
      13.1 respectively. The overall morbidity and mortality rates were 18.4% (30
      patients) and 28.8% (47 patients) respectively. In Group A the mortality rate was
      23.3% (24 patients) and the morbidity rate was 33.9% (35 patients). In Group B
      mortality and morbidity rates were 369% (17 patients) and 43.5% (20 patients)
      respectively. It was shown that the presence of both thoracic and abdominal
      injuries significantly increases the risk of mortality and morbidity. In patients
      with predominantly thoracic injuries, NISS proved to be the more reliable score,
      while ISS appeared to be more accurate in evaluating patients with injuries
      affecting more than one region of the body.

PMID- 21090558
TI  - Penis ligaments: their use in "increasing" the size of the penis in penile
      augmentation procedures. Anatomical description in human cadavers and clinical
      results of a phalloplasty series.
AB  - AIM: To present in human cadavers the anatomical basis of penis lengthening
      operations and reproduce this technique in a group of patients. MATERIALS OF
      STUDY: Penis ligaments in ten human cadavers were identified and dissected
      releasing the penis from its fixation to pubic arch. The same technique was
      applied to a group of forty patients that demanded a penis lengthening operation.
      RESULTS: The dissection of penis ligaments increases the distance pubic bone-tip
      of the penis for 3.1 +/- 0.6 cm. In patients, the increase in length 12 months
      post-operatively was 3.5 +/- 1.3 cm (2.3-5.1 cm) flaccid and 1.8 +/- 1.4 cm (1.4
      3.2 cm) erect. There was a statistically significant difference (p < 0.005)
      between preoperative and postoperative status. The overall satisfaction rate was
      67.5%. DISCUSSION: Cadavers study shows that this technique offers significant
      mobilization of the penis with a 3 cm gain, while on living tissue it has similar
      results. Anatomical parameters that might influence the final outcome of the
      operation are the length (antero-posterior dimension) of the pubic arch
      (corresponds to the length of the ligament), its angle with the horizontal level,
      the amount of the fatty tissue in the pubic area and the angle of the
      repositioning of the penis. CONCLUSIONS: Division of ligaments of the penis
      increases its apparent length. Significant anatomical parameters are the length
      of the pubic arch, its angle with the horizontal level, the amount of the fatty
      tissue in the pubic area and the angle of the repositioning of the penis.

PMID- 21090559
TI  - Unusual location of hydatid cyst: the posterior leaflet of tricuspid valve.
AB  - Hydatid Cyst disease involves the heart in 0.02-2% of the cases. It can appear
      with symptoms very similar to coronary artery disease, cardiac valvular disease
      and pericarditis. We present a case of hydatid cyst that was located on the
      posterior tricuspid leaflet and that caused tricuspid regurgitation in 37 year
      old female patient who has gone through hydatid cyst excision from the bilateral
      lungs with median sternotomy 2 years ago. In addition to the right atrial and
      ventricular dilatation, second degree tricuspid regurgitation and significant
      pulmonary hypertension was found. The 2 x 2 cm smooth surfaced mass was resected
      from the posterior leaflet of the tricuspid valve and the defect was closed with
      suture with the aid of cardiopulmonary bypass. The patient followed with long
      term albendazole treatment. Cardiac echinococcosis should be kept in mind in some
      patients throughout their life with a history of previous hydatid cyst disease.
      Surgical excision without rupture is the treatment of choice for cardiac hydatid
      cyst, with following medical therapy in order to prevent recurrence.

PMID- 21090560
TI  - Pancreatic pseudocyst-inferior vena cava fistula causing caval stenosis, left
      renal vein thrombosis, subcutaneous fat necrosis, arthritis and
      dysfibrinogenemia.
AB  - AIM: We describe the case of a 38 year old man, with a story of alcohol abuse,
      who developed a very painful nodular subcutaneous fat necrosis, fever and
      polyarthritis, denying any abdominal symptoms due to a pancreatic pseudocyst
      inferior vena cava fistula. MATERIAL OF STUDY: The authors discuss the unusual
      and protracted course with intermittent hyperamylasemia and hyperlipasemia
      related to clinical manifestations such as subcutaneous fat necrosis,
      polyarthritis, pleural effusion and dysfibrinogenemia, and vascular complications
      as inferior vena cava stenosis and left renal vein thrombosis without abdominal
      symptomatology. RESULTS: After ultrasonograms and CT Scans showing a 3-4 cm cyst
      at the pancreatic head with a solid bud protruding into the pseudocystic cavity,
      and an ERCP showing a communication between the pancreatic duct and the
      pseudocyst but failing in demonstrating the vascular fistula, the patient
      underwent a Roux-en-y pseudocyst-jejunostomy and suture of the caval
      communication leading to complete recovery with normalization of laboratory
      findings. DISCUSSION: In our case, the locally sclerosing activity of the enzymes
      in the endothelium led to a communication between the inferior vena cava and the
      pseudocyst and to a complete thrombosis of the left renal vein and to a stenosis
      of the inferior vena cava itself The fluctuance of the symptomatology severity
      was probably due to an intermittent opening of the passage between pseudocyst and
      vena cava. Such a clinical case, to the author knowledge, has never been
      reported. CONCLUSION: When in presence of very high levels of amylasemia and
      lipasemia in spite of the paucity of abdominal symptomatology, and the onset of
      unusual complications such as panniculitis, pleural effusion, arthritis and
      coagulative disorders, a pancreatic pseudocyst-inferior vena cava fistula should
      be kept in consideration during diagnosis.

PMID- 21090561
TI  - Single port laparoscopically assisted hysterectomy with the TriPort system. A
      case report and review of the literature.
AB  - AIM: We report our recent experience with the TriPort system (trademark of
      Advanced Surgical Concepts, Wicklow, Ireland) to perform a laparoscopically
      assisted hysterectomy via a single periumbilical incision. CASE REPORT: A 48-year
      old multiparous woman was referred to us on March 2009 because of
      menometrorrhagia and uterine fibroids. RESULTS: The procedure was performed
      without intraoperative complications. The weight of the uterus was 360 gr. At the
      10 months follow-up the patient did not refer any problem. DISCUSSION: Although
      our experience represented a potentially difficult surgery because of the size of
      the uterus, severe adhesions (two previous caesarean sessions) and the lack of
      experience with the new system, the procedure demonstrated to be feasible. As for
      our knowledge the present report represents the first case of single port
      laparoscopically assisted hysterectomy performed with the TriPort system in
      Italy. CONCLUSION: Single port laparoscopy is feasible and could potentially
      decrease postoperative pain as well as increase patient satisfaction. Although
      the early experience with TriPort system is promising, experienced laparoscopic
      skills are essential for the safe and effective performing of the procedure.

PMID- 21090562
TI  - Pheochromocytoma during pregnancy treated by surgery. A case report and the
      review of the literature.
AB  - INTRODUCTION: Prenatal diagnosis of pheocromocytoma, although rare, is important
      as it allows a reduction in both maternal mortality and foetal loss.
      Pheocromocytoma operated on in the first trimester of pregnancy with survival of
      both patient and foetus is rare in literature. Our case was operated on with
      success after a correct and early diagnosis was obtained despite a chronic
      hypertension which existed long before pregnancy. Our case study well illustrates
      that a correct multidisciplinary approach involving endocrinologists,
      anesthesiologists, surgeons and gynecologists is fundamental for a positive
      outcome. CASE REPORT: The case of a white caucasian pregnant woman at 13th weeks
      of gestation with pheocromocytoma and severe and unstable hypertension that could
      not be pharmacologically controlled is described. Morphological diagnosis was
      safely obtained by Magnetic Resonance Imaging (MRI) without intravenous medium
      contrast agent. Pre-operative treatment consisted of therapy with alpha-blockers
      and rehydration. Adrenalectomy was performed through a laparotomy. Postoperative
      treatment consisted of rehydration and ephedrine continued until the fourth post
      operative day. The post-operative period was uneventful and a new ultrasound (US)
      scan confirmed foetal vitality. The patient was discharged seven days after
      surgery. A live newborn was physiologically delivered after a nine-month
      pregnancy. CONCLUSION: A correct diagnosis in all pregnant women with severe
      hypertension particularly those not screened for secondary hypertension and a
      multidisciplinary management are mandatory to obtain optimal results and avoid
      deleterious effects at delivery.

PMID- 21090563
TI  - Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in
      dysregulation of gastrointestinal immunity in patients with advanced melanoma.
AB  - Blockade of cytotoxic T-lymphocyte antigen-4 (CTLA-4) by ipilimumab leads to
      immune-mediated tumor regression and immune-related adverse events (irAEs),
      including diarrhea and colitis. The current analyses were undertaken to promote
      an understanding of the underlying mechanism of action and to identify potential
      biomarkers that could help in the prediction and management of ipilimumab-induced
      gastrointestinal irAEs. Treatment-naive or previously treated patients with
      unresectable stage III/IV melanoma (n = 115) received open-label ipilimumab (10
      mg/kg every 3 weeks for four doses) and were randomized to receive concomitant
      blinded prophylactic oral budesonide (9 mg/d with gradual taper through week 16)
      or placebo. Outcome measures included histologic assessment of bowel biopsies and
      assessment of serologic markers of inflammatory bowel disease (IBD), fecal
      calprotectin levels, and polymorphisms in immune-related genes. Ipilimumab
      resulted in dysregulation of gastrointestinal mucosal immunity as evidenced by
      altered antibody levels to enteric flora, inflammatory cell infiltration into
      gastrointestinal mucosa, and increased fecal calprotectin associated with
      diarrhea and clinical evidence of colitis. The pattern of ipilimumab-induced
      antibody titers to microbial flora and the histologic features and location of
      the inflammation were distinct from classic IBD. Prophylactic budesonide did not
      prevent ipilimumab-induced bowel inflammation. Despite an observed association
      between colonic inflammation and grade 2 or higher diarrhea, no baseline
      biomarkers could reliably predict development of gastrointestinal toxicity.
      Although classic IBD and ipilimumab-related gastrointestinal toxicity are both
      immune mediated, the observed pattern of biomarkers suggests ipilimumab-related
      gastrointestinal toxicity may be a distinct clinicopathologic entity.

PMID- 21090564
TI  - Identification of botanical biomarkers in Argentinean Diplotaxis honeys:
      flavonoids and glucosinolates.
AB  - To select and establish floral biomarkers of the botanical origin of Diplotaxis
      tenuifolia honeys, the flavonoids and glucosinolates present in bee-deposited
      nectar collected from hive combs (unripe honey) and mature honey from the same
      hives fron which the unripe honey samples were collected were analyzed by LC-UV
      PAD-ESI-MS(n). Glycosidic conjugates of the flavonols quercetin, kaempferol, and
      isorhamnetin were detected and characterized in unripe honey. D. tenuifolia
      mature honeys contained the aglycones kaempferol, quercetin, and isorhamnetin.
      The differences between the phenolic profiles of mature honey and freshly
      deposited honey could be due to hydrolytic enzymatic activities. Aliphatic and
      indole glucososinolates were analyzed in unripe and mature honeys, this being the
      first report of the detection and characterization of glucosinolates as honey
      constituents. Moreover, these honey samples contained different amounts of
      propolis-derived flavonoid aglycones (1765-3171 MUg/100 g) and hydroxycinnamic
      acid derivatives (29-1514 MUg/100 g). Propolis flavonoids were already present in
      the freshly deposited nectar, showing that the incorporation of these compounds
      to honey occurs at the early steps of honey production. The flavonoids quercetin,
      kaempferol, and isorhamnetin and the glucosinolates detected in the samples could
      be used as complementary biomarkers for the determination of the floral origin of
      Argentinean Diplotaxis honeys.

PMID- 21090565
TI  - Enhanced stability and intracellular accumulation of quercetin by protection of
      the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl
      (POM) promoiety.
AB  - In order to increase stability of quercetin, its metabolically and chemically
      susceptible hydroxyl groups 7-OH and 3-OH respectively were transiently blocked
      with a pivaloxymethyl (POM) promoiety to provide two novel quercetin conjugates
      [7-O-POM-Q, 3-O-POM-Q]. In the absence of stabilizer (ascorbic acid), the
      synthesized conjugates showed significantly increased stability in cell culture
      media [t(1/2) = 4 h, 52 h] compared with quercetin (t(1/2) < 30 min) and
      quercetin prodrug 1 (t(1/2) = 0.8 h). In addition, the quercetin conjugate 2
      underwent efficient cellular uptake and intracellular levels of its hydrolysis
      product, quercetin, were maintained up to 12 h. Stability and intracellular
      accumulation of were demonstrated by its stabilizer-independent cytostatic effect
      and induction of apoptotic cell death. Even though was more stable than, it
      failed to penetrate cell membranes. However, the remarkable stability of warrants
      further investigation of quercetin conjugates with various promoieties at the 3
      OH position.

PMID- 21090566
TI  - Performance of soil-applied FeEDDHA isomers in delivering Fe to soybean plants in
      relation to the moment of application.
AB  - FeEDDHA (iron(3+) ethylenediamine-N,N'-bis(hydroxyphenylacetic acid) products are
      commonly applied to mend and prevent Fe deficiency chlorosis in soil-grown crops.
      Plants mainly take up Fe in the progressed vegetative and in the reproductive
      stages. This study examined which of the principal constituents of FeEDDHA
      products (the isomers racemic o,o-FeEDDHA, meso o,o-FeEDDHA, and o,p-FeEDDHA),
      most effectively meets the Fe requirements of soybean plants (Glycine max (L.)
      Merr.) grown on calcareous soil in the aforementioned growth stages. FeEDDHA
      isomers were applied once, separately or in mixtures, at t = 0, in the progressed
      vegetative stage or in the reproductive stage. o,p-FeEDDHA did not significantly
      contribute to Fe uptake in either growth stage. Both racemic and meso o,o-FeEDDHA
      were effective in supplying plants with Fe, approximately to the same extent. The
      moment of application had a significant effect on yield and FeEDDHA pore water
      concentrations at harvest, but not on Fe uptake. To optimize yield while
      minimizing FeEDDHA dosage, FeEDDHA is best applied to soybean plants prior to the
      onset of chorosis.

PMID- 21090567
TI  - A selective NMR method for detecting choline containing compounds in liver
      tissue: the 1H-14N HSQC experiment.
AB  - The feasibility of a (1)H-(14)N HSQC experiment on tissues is demonstrated with a
      mouse liver based on the J couplings between the protons and the quadrupolar
      nucleus (14)N in choline. Free choline, phosphocholine, and
      glycerolphosphocholine (1)H-(14)N HSQC signals were selectively observed with all
      unwanted signals cleanly suppressed. The CH2O signals were well resolved in the
      two-dimensional spectrum, which can be used for quantitative analyses.

PMID- 21090568
TI  - Two-dimensional electrophoresis based proteomic analysis of the pea (Pisum
      sativum) in response to Mycosphaerella pinodes.
AB  - Responses to Mycosphaerella pinodes in pea were studied by using a proteomics
      approach. Two-dimensional electrophoresis (2-DE) was used in order to compare the
      leaf proteome of two pea cultivars displaying different phenotypes (susceptible
      and partial resistance to the fungus), as well as in response to the inoculation.
      Multivariate statistical analysis identified 84 differential protein spots under
      the experimental conditions (cultivars/treatments). All of these 84 protein spots
      were subjected to MALDI-TOF/TOF mass spectrometry to deduce their possible
      functions. A total of 31 proteins were identified using a combination of peptide
      mass fingerprinting (PMF) and MSMS fragmentation. Most of the identified proteins
      corresponded to enzymes belonging to photosynthesis, metabolism,
      transcription/translation and defense and stress categories. Results are
      discussed in terms of responses to pathogens.

PMID- 21090569
TI  - Electron spin resonance studies of silicon difluoride.

PMID- 21090570
TI  - Noncovalent liposome linkage and miniaturization of capsosomes for drug delivery.
AB  - We report the synthesis of poly(methacrylic acid)-co-(oleyl methacrylate) with
      three different amounts of oleyl methacrylate and compare the ability of these
      polymers with that of poly(methacrylic acid)-co-(cholesteryl methacrylate)
      (PMA(c)) to noncovalently anchor liposomes to polymer layers. We subsequently
      assembled ~1 MUm diameter PMA(c)-based capsosomes, polymer hydrogel capsules that
      contain up to ~2000 liposomal subcompartments, and investigate the potential of
      these carriers to deliver water-insoluble drugs by encapsulating two different
      antitumor compounds, thiocoraline or paclitaxel, into the liposomes. The
      viability of lung cancer cells is used to substantiate the cargo concentration
      dependent activity of the capsosomes. These findings cover several crucial
      aspects for the application of capsosomes as potential drug delivery vehicles.

PMID- 21090571
TI  - Comparative modeling approaches for personal exposure to particle-associated PAH.
AB  - Several models for simulation of personal exposure (PE) to particle-associated
      polycyclic aromatic hydrocarbons (PAH) have been developed and tested. The
      modeling approaches include linear regression models (Model 1), time activity
      weighted models (Models 2 and 3), a hybrid model (Model 4), a univariate linear
      model (Model 5), and machine learning technique models (Model 6 and 7). The
      hybrid model (Model 4), which utilizes microenvironment data derived from time
      activity diaries (TAD) with the implementation of add-on variables to account for
      external factors that might affect PE, proved to be the best regression model
      (R(2) for B(a)P = 0.346, p < 0.01; N = 68). This model was compared with results
      from two machine learning techniques, namely decision trees (Model 6) and neural
      networks (Model 7), which represent an innovative approach to PE modeling. The
      neural network model was promising in giving higher correlation coefficient
      results for all PAH (R(2) for B(a)P = 0.567, p < 0.01; N = 68) and good
      performance with the smaller test data set (R(2) for B(a)P = 0.640, p < 0.01; N =
      23). Decision tree accuracies (Model 6) which assess how precisely the algorithm
      can determine the correct classification of a PE concentration range indicate
      good performance, but this is not comparable to the other models through R(2)
      values. Using neural networks (Model 7) showed significant improvements over the
      performance of hybrid Model 4 and the univariate general linear Model 5 for test
      samples (not used in developing the models). The worst performance was given by
      linear regression Models 1 to 3 based solely on home and workplace concentrations
      and time-activity data.

PMID- 21090572
TI  - Protein microarrays based on polymer brushes prepared via surface-initiated atom
      transfer radical polymerization.
AB  - Polymer brushes represent an interesting platform for the development of high
      capacity protein binding surfaces. Whereas the protein binding properties of
      polymer brushes have been investigated before, this manuscript evaluates the
      feasibility of poly(glycidyl methacrylate) (PGMA) and PGMA-co-poly(2
      (diethylamino)ethyl methacrylate) (PGMA-co-PDEAEMA) (co)polymer brushes grown via
      surface-initiated atom transfer radical polymerization (SI-ATRP) as protein
      reactive substrates in a commercially available microarray system using tantalum
      pentoxide-coated optical waveguide-based chips. The performance of the polymer
      brush-based protein microarray chips is assessed using commercially available
      dodecylphosphate (DDP)-modified chips as the benchmark. In contrast to the 2D
      planar, DDP-coated chips, the polymer-brush-covered chips represent a 3D sampling
      volume. This was reflected in the results of protein immobilization studies,
      which indicated that the polymer-brush-based coatings had a higher protein
      binding capacity as compared to the reference substrates. The protein binding
      capacity of the polymer-brush-based coatings was found to increase with
      increasing brush thickness and could also be enhanced by copolymerization of 2
      (diethylamino)ethyl methacrylate (DEAEMA), which catalyzes epoxide ring-opening
      of the glycidyl methacrylate (GMA) units. The performance of the polymer-brush
      based microarray chips was evaluated in two proof-of-concept microarray
      experiments, which involved the detection of biotin-streptavidin binding as well
      as a model TNFalpha reverse assay. These experiments revealed that the use of
      polymer-brush-modified microarray chips resulted not only in the highest absolute
      fluorescence readouts, reflecting the 3D nature and enhanced sampling volume
      provided by the brush coating, but also in significantly enhanced signal-to-noise
      ratios. These characteristics make the proposed polymer brushes an attractive
      alternative to commercially available, 2D microarray surface coatings.

PMID- 21090573
TI  - Colloidal alpha-Al2O3 Europium(III) and humic substances interactions: a
      macroscopic and spectroscopic study.
AB  - Eu(III) sorption onto alpha-Al(2)O(3) in the presence of purified Aldrich humic
      acid (PAHA) is studied by batch experiments and time-resolved laser-induced
      luminescence spectroscopy of Eu(III). Experiments are conducted at varying pH, at
      0.1 mol/L NaClO(4), 10(-6) mol/L Eu(III), 1 g/L alpha-Al(2)O(3) and 28 mg/L PAHA,
      which assured a complete Eu(III)-PAHA complexation. Adsorption of Eu(III)
      presents the expected pH-edge at 7, which is modified by addition of PAHA.
      Presence of Eu(III) slightly increases PAHA sorption throughout the pH range. The
      evolutions of luminescence spectra and decay times of the binary systems, that
      is, Eu(III)/alpha-Al(2)O(3) and Eu(III)/PAHA, indicate a progressive surface- and
      humic-complexation with increasing pH. The typical biexponential luminescence
      decay in Eu(III)/PAHA system is also recorded; the fastest deactivation depending
      barely on pH. In ternary Eu(III)/PAHA/alpha-Al(2)O(3) system, the existence of a
      luminescence biexponential decay for all pH means that Eu(III) is always in the
      direct neighborhood of the humic substance. Below pH 7, the spectra of the
      ternary system (Eu(III)/PAHA/alpha-Al(2)O(3)) are not different from the ones of
      Eu(III)/PAHA system, implying the same complex symmetry. Nevertheless, the
      increase of luminescence decay time points to a change in PAHA conformation onto
      the surface.

PMID- 21090574
TI  - Electro-active shape memory properties of poly(epsilon
      caprolactone)/functionalized multiwalled carbon nanotube nanocomposite.
AB  - One type of electroactive shape memory nanocomposite was fabricated, including
      cross-linked poly(epsilon-caprolactone) (cPCL) and conductive multiwalled carbon
      nanotubes (MWNTs). The cross-linking reaction of the pristine poly(epsilon
      caprolactone) (PCL) was realized by using benzoyl peroxide (BPO) as an initiator.
      The raw MWNTs (Raw-M) were prefunctionalized by acid-oxidation process and
      covalent grafting with poly (ethylene glycol) (PEG), respectively. Three kinds of
      nanocomposites containing cPCL/Raw-M, cPCL/acid-oxidation MWNTs (AO-M) and
      cPCL/PEG grafted MWNTs (PEG-M) were obtained, and the mechanical, electrical and
      shape memory properties were further investigated. The influence of in vitro
      degradation on their shape memory and mechanical properties was also evaluated.
      The methyl thiazolyl tetrazolium (MTT) assay was performed to estimate their
      biocompatibility. The results displayed that these nanocomposites could perform
      favorable shape memory recovery both in hot water at 55  degrees C and in
      electric field with 50 V applied voltage. In addition, compared with cPCL/Raw-M
      and cPCL/AO-M, cPCL/PEG-M composite possessed more favorable properties such as
      mechanical, biocompatible, and electroactive shape memory functions. Therefore,
      the nanocomposite may be potential for application as smart bioactuators in
      biomedical field.

PMID- 21090575
TI  - Palladium-catalyzed asymmetric synthesis of axially chiral allenylsilanes and
      their application to SE2' chirality transfer reactions.
AB  - Stepwise application of the Pd-catalyzed S(N)2' reaction and the desilylative
      S(E)2' reaction to the ambivalent 2-bromo-1-silyl-1,3-dienes provides a novel
      route to the highly enantioselective construction of tertiary and quaternary
      propargylic stereogenic centers via axially chiral allenylsilanes.

PMID- 21090576
TI  - Tuning photosensitized singlet oxygen generation efficiency of novel aza-BODIPY
      dyes.
AB  - Novel aza-BODIPY derivatives substituted with heavy atoms such as bromine and
      iodine were synthesized, and their triplet and singlet oxygen generation
      efficiencies have been investigated. These derivatives showed absorption in the
      NIR region with high molar extinction coefficients. The dye substituted with four
      iodine atoms showed yields of Phi(T) = 0.78 and Phi((1)O(2)) = 0.70, which are
      the highest values so far obtained for the aza-BODIPY derivatives.

PMID- 21090577
TI  - Elemental depth profiling of fluoridated hydroxyapatite: saving your dentition by
      the skin of your teeth?
AB  - Structural and chemical changes that arise from fluoridation of hydroxyapatite
      (Ca(5)(PO(4))(3)OH or "HAp"), as representing the synthetic counterpart of tooth
      enamel, are investigated by X-ray photoelectron spectroscopy (XPS). Elemental
      depth profiles with a depth resolution on the nanometer scale were determined to
      reveal the effect of fluoridation in neutral (pH = 6.2) and acidic agents (pH =
      4.2). With respect to the chemical composition and the crystal structure, XPS
      depth profiling reveals different effects of the two treatments. In both cases,
      however, the fluoridation affects the surface only on the nanometer scale, which
      is in contrast to recent literature with respect to XPS analysis on dental
      fluoridation, where depth profiles of F extending to several micrometers were
      reported. In addition to the elemental depth profiles, as published in various
      other studies, we also present quantitative depth profiles of the compounds
      CaF(2), Ca(OH)(2), and fluorapatite (FAp) that were recently proposed by a three
      layer model concerning the fluoridation of HAp in an acidic agent. The analysis
      of our experimental data exactly reproduces the structural order of this model,
      however, on a scale that differs by nearly 2 orders of magnitude from previous
      predictions. The results also reveal that the amount of Ca(OH)(2) and FAp is
      small compared to that of CaF(2). Therefore, it has to be asked whether such
      narrow Ca(OH)(2) and FAp layers really can act as protective layers for the
      enamel.

PMID- 21090578
TI  - Grafted glycopolymer-based receptor mimics on polymer support for selective
      adhesion of bacteria.
AB  - A sugar-containing monomer (2-lactobionamidoethyl methacrylate, LAMA) was grafted
      on a polypropylene (PP) microfiltration membrane surface by UV-induced graft
      copolymerization. The degree of grafting can be controlled by variation of
      monomer concentration, UV irradiation time, and photoinitiator concentration.
      Fourier transform infrared spectroscopy and scanning electron microscopy were
      employed to confirm the surface modification on the membranes. The water contact
      angle was used to evaluate the hydrophilicity change of the membrane surface
      before and after modification. Bacteria capture experiments showed that the
      membrane could selectively bind E. faecalis while adhesion of S. maltophilia was
      not influenced by the functionalization of PP with grafted poly(LAMA). The
      adhesion of E. faecalis onto poly(LAMA) grafted membrane could be inhibited by
      200 mM galactose solution; however, glucose solution showed no inhibition effect.
      Moreover, occupying sugar residues on the membrane surface primarily by a
      galactose targeting lectin, peanut agglutinin, could significantly suppress the
      following adhesion of E. faecalis. All these results clearly demonstrate that
      this poly(LAMA) grafted PP membrane can selectively capture E. faecalis and that
      this selection is based on the interaction between galactose side groups on
      grafted flexible functional polymer chains on the membrane surface and galactose
      binding protein on the E. faecalis cell membrane.

PMID- 21090579
TI  - Enhancement of CO2 sorption uptake on hydrotalcite by impregnation with K2CO3.
AB  - The awareness of symptoms of global warming and its seriousness urges the
      development of technologies to reduce greenhouse gas emissions. Carbon dioxide
      (CO(2)) is a representative greenhouse gas, and numerous methods to capture and
      storage CO(2) have been considered. Recently, the technology to remove high
      temperature CO(2) by sorption has received lots of attention. In this study,
      hydrotalcite, which has been known to have CO(2) sorption capability at high
      temperature, was impregnated with K(2)CO(3) to enhance CO(2) sorption uptake, and
      the mechanism of CO(2) sorption enhancement on K(2)CO(3)-promoted hydrotalcite
      was investigated. Thermogravimetric analysis was used to measure equilibrium
      CO(2) sorption uptake and to estimate CO(2) sorption kinetics. The analyses based
      on N(2) gas physisorption, X-ray diffractometry, Fourier transform infrared
      spectrometry, Raman spectrometry, transmission electron microscopy, scanning
      electron microscopy, and energy dispersive X-ray spectroscopy were carried out to
      elucidate the characteristics of sorbents and the mechanism of enhanced CO(2)
      sorption. The equilibrium CO(2) sorption uptake on hydrotalcite could be
      increased up to 10 times by impregnation with K(2)CO(3), and there was an optimal
      amount of K(2)CO(3) for a maximum equilibrium CO(2) sorption uptake. In the
      K(2)CO(3)-promoted hydrotalcite, K(2)CO(3) was incorporated without changing the
      structure of hydrotalcite and it was thermally stabilized, resulting in the
      enhanced equilibrium CO(2) sorption uptake and fast CO(2) sorption kinetics.

PMID- 21090580
TI  - Investigation of a catalyst ink dispersion using both ultra-small-angle X-ray
      scattering and cryogenic TEM.
AB  - The dispersion of Nafion ionomer particles and Pt/C catalyst aggregates in liquid
      media was studied using both ultra-small-angle X-ray scattering (USAXS) and
      cryogenic TEM. A systematic approach was taken to study first the dispersion of
      each component (i.e., ionomer particles and Pt/C aggregates), then the
      combination of the components, and last the catalyst ink. Multiple-level curve
      fitting was used to extract the particle size, size distribution, and geometry of
      the Pt/C aggregates and the Nafion particles in liquid media from the scattering
      data. The results suggest that the particle size, size distribution, and geometry
      are not uniform throughout the systems but rather vary significantly. It was
      found that the interaction of each component (i.e., the Nafion ionomer particles
      and the Pt/C aggregates) occurs in the dispersion. Cryogenic TEM was used to
      observe the size and geometry of the particles in liquid directly and to validate
      the scattering results. The TEM results showed excellent agreement.

PMID- 21090581
TI  - Renewable nanocomposite layer-by-layer assembled catalytic interfaces for
      biosensing applications.
AB  - A novel, easily renewable nanocomposite interface based on layer-by-layer (LbL)
      assembled cationic/anionic layers of carbon nanotubes customized with biopolymers
      is reported. A simple approach is proposed to fabricate a nanoscale structure
      composed of alternating layers of oxidized multiwalled carbon nanotubes upon
      which is immobilized either the cationic enzyme organophosphorus hydrolase (OPH;
      MWNT-OPH) or the anionic DNA (MWNT-DNA). The presence of carbon nanotubes with
      large surface area, high aspect ratio and excellent conductivity provides
      reliable immobilization of enzyme at the interface and promotes better electron
      transfer rates. The oxidized MWNTs were characterized by thermogravimetric
      analysis and Raman spectroscopy. Fourier transform infrared spectroscopy showed
      the surface functionalization of the MWNTs and successful immobilization of OPH
      on the MWNTs. Scanning electron microscopy images revealed that MWNTs were
      shortened during sonication and that LbL of the MWNT/biopolymer conjugates
      resulted in a continuous surface with a layered structure. The catalytic activity
      of the biopolymer layers was characterized using absorption spectroscopy and
      electrochemical analysis. Experimental results show that this approach yields an
      easily fabricated catalytic multilayer with well-defined structures and
      properties for biosensing applications whose interface can be reactivated via a
      simple procedure. In addition, this approach results in a biosensor with
      excellent sensitivity, a reliable calibration profile, and stable electrochemical
      response.

PMID- 21090582
TI  - Effect of top dielectric medium on gate capacitance of graphene field effect
      transistors: implications in mobility measurements and sensor applications.
AB  - We have carried out Hall measurement on back-gated graphene field effect
      transistors (FET) with and without a top dielectric medium. The gate efficiency
      increases by up to 2 orders of magnitude in the presence of a high kappa top
      dielectric medium, but the mobility does not change significantly. Our
      measurement further shows that the back-gate capacitance is enhanced dramatically
      by the top dielectric medium, and the enhancement increases with the size of the
      top dielectric medium. Our work strongly suggests that the previously reported
      top dielectric medium-induced charge transport properties of graphene FETs are
      possibly due to the increase of gate capacitance, rather than enhancement of
      carrier mobility. 

PMID- 21090583
TI  - Nitrogen/boron doping position dependence of the electronic properties of a
      triangular graphene.
AB  - We investigate the effect of N/B doping on the electronic properties for a zero
      dimensional zigzag-edged triangular graphene, wherein two sets of sublattices are
      unbalanced, using density functional theory (DFT). We find that the
      substitutional N/B atom energetically prefers to distribute in the major
      sublattice. After the N/B doping, the net spin for triangular graphene is reduced
      and full or partial depolarization occurs depending on doping sites. Our DFT
      calculations show that the triangular graphene with N/B doped in the major
      sublattice has a larger energy gap, and the electronic properties depend on the
      doping position. There is an impurity state below or above the Fermi level for
      the N/B-doped triangular graphene, depending on the sublattice at which the
      dopant locates. The dependence of the electronic properties on doping position is
      attributed to the competition between the Coulomb attraction of N(+) (B(-)) and
      the correlation with nonbonding states for the extra charge introduced by the N/B
      atom.

PMID- 21090584
TI  - Nanostructure-mediated launching and detection of 2D surface plasmons.
AB  - Au nanoparticles deposited on a metallic film act as nanoantenna receivers and
      transmitters for the coupling of free-space radiation into, and out of, 2D
      surface plasmons. Nanosteps, sub-10-nm gaps between metallic films of differing
      thickness, can also launch and detect surface plasmons. Here we use both types of
      structures to locally launch propagating surface plasmon waves and probe their
      properties. Nanoparticle-launched surface plasmons emerge as two lobes of
      nominally 90 degree angular width, propagating along the direction of incident
      polarization. Alternatively, plasmons can be launched unidirectionally, by
      asymmetric illumination of a nanoparticle receiver.

PMID- 21090585
TI  - Free-standing optical gold bowtie nanoantenna with variable gap size for enhanced
      Raman spectroscopy.
AB  - We describe plasmonic interactions in suspended gold bowtie nanoantenna leading
      to strong electromagnetic field (E) enhancements. Surface-enhanced Raman
      scattering (SERS) was used to demonstrate the performance of the nanoantenna. In
      addition to the well-known gap size dependence, up to 2 orders of magnitude
      additional enhancement is observed with elevated bowties. The overall behavior is
      described by a SERS enhancement factor exceeding 10(11) along with an anomalously
      weak power law dependence of E on the gap size in a range from 8 to 50 nm that is
      attributed to a plasmonic nanocavity effect occurring when the plasmonic
      interactions enter a strongly coupled regime. 

PMID- 21090586
TI  - Preparation of amphiphilic polymer-functionalized carbon nanotubes for low
      protein-adsorption surfaces and protein-resistant membranes.
AB  - Multiwalled carbon nanotubes functionalized with poly(sulfone) (PSF) and
      poly(sulfobetaine methacrylate) (PSBMA) (MWNT-PSF/PSBMA) have been prepared
      through sequential atom transfer radical polymerization. The structure of MWNT
      PSF/PSBMA hybrid has been characterized with FTIR, Raman spectroscopy, and high
      resolution transmission electron microscopy. Incorporation of PSBMA chains to
      MWNTs introduces amphiphilic and protein-resistant properties to MWNT-PSF/PSBMA.
      Addition of 1 wt % MWNT-PSF/PSBMA to PSF films significantly improves their
      protein-resistant characteristic, as the composite films show a 4.4% of protein
      adsorption compared to poly(styrene) Petri dishes. The PSF/MWNT-PSF/PSBMA
      composite has been applied to prepare antifouling ultrafiltration membranes for
      protein separation. This work demonstrates an effective and convenient approach
      to prepare low-protein-adsorption surfaces and antifouling membranes.

PMID- 21090587
TI  - Gold mesostructures with tailored surface topography and their self-assembly
      arrays for surface-enhanced Raman spectroscopy.
AB  - We report a facile particle mediated aggregation protocol to synthesize "sea
      urchin"-like gold mesoparticles with tailored surface topography via a secondary
      nucleation and growth process. Surprisingly, these multitip Au mesoparticles are
      capable of self-assembling into monolayer or multiple layer arrays on Si
      substrates with a convincing reproducibility and homogeneity over large areas.
      Raman measurements show that these individual sea urchin-like multitipped gold
      mesoparticles exhibit a high enhancement of surface-enhanced Raman scattering
      (SERS). In addition, the sea urchin-like mesoparticle arrays display a further
      enhancement of SERS by 1 or 2 orders of magnitude over the individual
      mesoparticle due to the formation of additional hot spots between the particles.
      The current protocol stands out as a potentially interesting approach for the
      fabrication of technologically important SERS-based sensors.

PMID- 21090588
TI  - Efavirenz binding site in HIV-1 reverse transcriptase monomers.
AB  - Efavirenz (EFV) is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI)
      used in the treatment of AIDS. NNRTIs bind in a hydrophobic pocket located in the
      p66 subunit of reverse transcriptase (RT), which is not present in crystal
      structures of RT without an inhibitor. Recent studies showed that monomeric forms
      of the p66 and p51 subunits bind efavirenz with micromolar affinity. The effect
      of efavirenz on the solution conformations of p66 and p51 monomers was studied by
      hydrogen-deuterium exchange mass spectrometry (HXMS) and Fourier transform ion
      cyclotron resonance mass spectrometry (FT-ICR MS). HXMS data reveal that five
      peptides, four of which contain efavirenz contact residues seen in the crystal
      structure of the RT-EFV complex, exhibit a reduced level of exchange in monomer
      EFV complexes. Moreover, peptide 232-246 undergoes slow cooperative unfolding
      refolding in the bound monomers, but at a rate much slower than that observed in
      the p66 subunit of the RT heterodimer [Seckler, J. M., Howard, K. J., Barkley, M.
      D., and Wintrode, P. L. (2009) Biochemistry 48, 7646-7655]. These results suggest
      that the efavirenz binding site on p66 and p51 monomers is similar to the NNRTI
      binding pocket in the p66 subunit of RT. Nanoelectrospray ionization FT-ICR mass
      spectra indicate that the intact monomers each have (at least) two different
      conformations. In the presence of efavirenz, the mass spectra change
      significantly and suggest that p51 adopts a single, more compact conformation,
      whereas p66 undergoes facile, electrospray-induced cleavage. The population shift
      is consistent with a selected-fit binding mechanism.

PMID- 21090589
TI  - HDAC6 and Ubp-M BUZ domains recognize specific C-terminal sequences of proteins.
AB  - The BUZ/Znf-UBP domain is a protein module found in the cytoplasmic deacetylase
      HDAC6, E3 ubiquitin ligase BRAP2/IMP, and a subfamily of ubiquitin-specific
      proteases. Although several BUZ domains have been shown to bind ubiquitin with
      high affinity by recognizing its C-terminal sequence (RLRGG-COOH), it is
      currently unknown whether the interaction is sequence-specific or whether the BUZ
      domains are capable of binding to proteins other than ubiquitin. In this work,
      the BUZ domains of HDAC6 and Ubp-M were subjected to screening against a one-bead
      one-compound (OBOC) peptide library that exhibited random peptide sequences with
      free C-termini. Sequence analysis of the selected binding peptides as well as
      alanine scanning studies revealed that the BUZ domains require a C-terminal Gly
      Gly motif for binding. At the more N-terminal positions, the two BUZ domains have
      distinct sequence specificities, allowing them to bind to different peptides
      and/or proteins. A database search of the human proteome on the basis of the BUZ
      domain specificities identified 11 and 24 potential partner proteins for Ubp-M
      and HDAC6 BUZ domains, respectively. Peptides corresponding to the C-terminal
      sequences of four of the predicted binding partners (FBXO11, histone H4, PTOV1,
      and FAT10) were synthesized and tested for binding to the BUZ domains by
      fluorescence polarization. All four peptides bound to the HDAC6 BUZ domain with
      low micromolar K(D) values and less tightly to the Ubp-M BUZ domain. Finally, in
      vitro pull-down assays showed that the Ubp-M BUZ domain was capable of binding to
      the histone H3-histone H4 tetramer protein complex. Our results suggest that BUZ
      domains are sequence-specific protein-binding modules, with each BUZ domain
      potentially binding to a different subset of proteins.

PMID- 21090590
TI  - Stereoselective 6pi-electron electrocyclic ring closures of 2-halo-amidotrienes
      via a remote 1,6-asymmetric induction.
AB  - A diastereoselective 6pi-electrocyclic ring closure employing halogen-substituted
      3-amidotrienes via a 1,6-remote asymmetric induction is described. This new
      asymmetric manifold for pericyclic ring closure further underscores the
      significance of the allenamide chemistry.

PMID- 21090591
TI  - Improved helix and kink characterization in membrane proteins allows evaluation
      of kink sequence predictors.
AB  - Although the alpha-helical secondary structure of proteins is well-defined, the
      exact causes and structures of helical kinks are not. This is especially
      important for transmembrane (TM) helices of integral membrane proteins, many of
      which contain kinks providing functional diversity despite predominantly helical
      structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to
      determine helical axes alongside positions and angles of helical kinks. Analysis
      of all nonredundant high-resolution alpha-helical membrane protein structures
      (842 TM helices from 205 polypeptide chains) revealed kinks in 64% of TM helices,
      demonstrating that a significantly greater proportion of TM helices are kinked
      than those indicated by previous analyses. The residue proline is over
      represented by a factor >5 if it is two or three residues C-terminal to a bend.
      Prolines also cause kinks with larger kink angles than other residues. However,
      only 33% of TM kinks are in proximity to a proline. Machine learning techniques
      were used to test for sequence-based predictors of kinks. Although kinks are
      somewhat predicted by sequence, kink formation appears to be driven predominantly
      by other factors. This study provides an improved view of the prevalence and
      architecture of kinks in helical membrane proteins and highlights the fundamental
      inaccuracy of the typical topological depiction of helical membrane proteins as
      series of ideal helices.

PMID- 21090592
TI  - Defective dicubane-like tetranuclear nickel(II) cyanate and azide nanoscale
      magnets.
AB  - Four tetrameric nickel(II) pseudohalide complexes have been synthesized and
      structurally, spectroscopically, and magnetically characterized. Compounds 1-3
      are isostructural and exhibit the general formula
      [Ni(2)(dpk.OH)(dpk.CH(3)O)(L)(H(2)O)](2)A(2).2H(2)O, where dpk = di-2
      pyridylketone; L = N(3)(-), and A = ClO(4)(-) for 1, L = NCO(-) and A = ClO(4)(-)
      for 2, and L = NCO(-) and A = NO(3)(-) for 3. The formula for 4 is
      [Ni(4)(dpk.OH)(3) (dpk.CH(3)O)(2)(NCO)](BF(4))(2).3H(2)O. The ligands dpk.OH(-)
      and dpk.CH(3)O(-) result from solvolysis and ulterior deprotonation of dpk in
      water and methanol, respectively. The four tetramers exhibit a dicubane-like core
      with two missing vertexes where the Ni(II) ions are connected through end-on
      pseudohalide and oxo bridges. Magnetic measurements showed that compounds 1-4 are
      ferromagnetic. The values of the exchange constants were determined by means of a
      theoretical model based on three different types of coupling. Thus, the
      calculated J values (J(1) = J(2), J(3), and D) were 5.6, 11.8, and 5.6 cm(-1) for
      1, 5.5, 12.0, and 5.6 cm(-1) for 2, 6.3, 4.9, and 6.2 cm(-1) for 3, and (J(1),
      J(2), J(3), and D) 6.9, 7.0, 15.2, and 4.8 cm(-1) for 4.

PMID- 21090594
TI  - Nickel-catalyzed cross-coupling of potassium aryl- and heteroaryltrifluoroborates
      with unactivated alkyl halides.
AB  - A method for the cross-coupling of alkyl electrophiles with various potassium
      aryl- and heteroaryltrifluoroborates has been developed. Nearly stoichiometric
      amounts of organoboron species could be employed to cross-couple a large variety
      of challenging heteroaryl nucleophiles. Several functional groups were tolerated
      on both the electrophilic and the nucleophilic partners. Chemoselective
      reactivity of C(sp(3))-Br bonds in the presence of C(sp(2))-Br bonds was
      achieved.

PMID- 21090593
TI  - Identification of SR3335 (ML-176): a synthetic RORalpha selective inverse
      agonist.
AB  - Several nuclear receptors (NRs) are still character-ized as orphan receptors
      because ligands have not yet been identified for these proteins. The retinoic
      acid receptor-related receptors (RORs) have no well-defined physiological
      ligands. Here, we describe the identification of a selective RORalpha synthetic
      ligand, SR3335 (ML-176). SR3335 directly binds to RORalpha, but not other RORs,
      and functions as a selective partial inverse agonist of RORalpha in cell-based
      assays. Furthermore, SR3335 suppresses the expression of endogenous RORalpha
      target genes in HepG2 involved in hepatic gluconeogenesis including glucose-6
      phosphatase and phosphoenolpyruvate carboxykinase. Pharmacokinetic studies
      indicate that SR3335 displays reasonable exposure following an ip injection into
      mice. We assess the ability of SR3335 to suppress gluconeogenesis in vivo using a
      diet-induced obesity (DIO) mouse model where the mice where treated with 15 mg/kg
      b.i.d., ip for 6 days followed by a pyruvate tolerance test. SR3335-treated mice
      displayed lower plasma glucose levels following the pyruvate challenge consistent
      with suppression of gluconeogenesis. Thus, we have identified the first selective
      synthetic RORalpha inverse agonist, and this compound can be utilized as a
      chemical tool to probe the function of this receptor both in vitro and in vivo.
      Additionally, our data suggests that RORalpha inverse agonists may hold utility
      for suppression of elevated hepatic glucose production in type 2 diabetics.

PMID- 21090595
TI  - EMBM - a new enzyme mechanism-based method for rational design of chemical sites
      of covalent inhibitors.
AB  - We introduce an enzyme mechanism-based method (EMBM) aimed at rational design of
      chemical sites (CS) of reaction coordinate analog inhibitors. The energy of
      valence reorganization of CS, caused by the formation of the enzyme-inhibitor
      covalent complex, is accounted for by new covalent descriptors W1 and W2. We
      considered CS fragments with a carbonyl reactivity center, like in native
      protease substrates. The W1 and W2 descriptors are calculated quantum
      mechanically on small molecular clusters simulating the reaction core of the
      formed covalent tetrahedral complex, anionic TC(O-) or neutral TC(OH). The
      modeling on a reaction core allows generation of various CS and corresponding
      TC(O-) and TC(OH) as universal building blocks of real inhibitors and their
      covalent complexes with serine or cysteine hydrolases. Moreover, the approach
      avoids the need for 3D structure of the target enzyme, so EMBM may be used for
      ligand-based design. We have built a chemical site of inhibitors (CSI) databank
      with pairs of W1 and W2 descriptors precalculated for both CH3O(-) and CH3S(-)
      nucleophiles for every collected CS fragment. We demonstrated that contribution
      of a CS fragment to the binding affinity of an inhibitor depends on both its
      covalent reorganization during the chemical transformation and its noncovalent
      interactions in the enzyme active site. Consequently, prediction of inhibitors
      binding trend can be done only by accounting for all of these factors, using W1
      and W2 in combination with noncovalent QSAR descriptors.

PMID- 21090597
TI  - Plastic deformation drives wrinkling, saddling, and wedging of annular bilayer
      nanostructures.
AB  - We describe the spontaneous wrinkling, saddling, and wedging of metallic, annular
      bilayer nanostructures driven by grain coalescence in one of the layers.
      Experiments revealed these different outcomes based on the dimensions of the
      annuli, and we find that the essential features are captured using finite element
      simulations of the plastic deformation in the metal bilayers. Our results show
      that the dimensions and nanomechanics associated with the plastic deformation of
      planar nanostructures can be important in forming complex three-dimensional
      nanostructures. 

PMID- 21090596
TI  - Recent advances in colloidal and interfacial phenomena involving liquid crystals.
AB  - This feature article describes recent advances in several areas of research
      involving the interfacial ordering of liquid crystals (LCs). The first advance
      revolves around the ordering of LCs at bio/chemically functionalized surfaces.
      Whereas the majority of past studies of surface-induced ordering of LCs have
      involved surfaces of solids that present a limited diversity of chemical
      functional groups (surfaces at which van der Waals forces dominate surface
      induced ordering), recent studies have moved to investigate the ordering of LCs
      on chemically complex surfaces. For example, surfaces decorated with biomolecules
      (e.g., oligopeptides and proteins) and transition-metal ions have been
      investigated, leading to an understanding of the roles that metal-ligand
      coordination interactions, electrical double layers, acid-base interactions, and
      hydrogen bonding can play in the interfacial ordering of LCs. The opportunity to
      create chemically responsive LCs capable of undergoing ordering transitions in
      the presence of targeted molecular events (e.g., ligand exchange around a metal
      center) has emerged from these fundamental studies. A second advance has focused
      on investigations of the ordering of LCs at interfaces with immiscible isotropic
      fluids, particularly water. In contrast to prior studies of surface-induced
      ordering of LCs on solid surfaces, LC-aqueous interfaces are deformable and
      molecules at these interfaces exhibit high levels of mobility and thus can
      reorganize in response to changes in the interfacial environment. A range of
      fundamental investigations involving these LC-aqueous interfaces have revealed
      that (i) the spatial and temporal characteristics of assemblies formed from
      biomolecular interactions can be reported by surface-driven ordering transitions
      in the LCs, (ii) the interfacial phase behavior of molecules and colloids can be
      coupled to (and manipulated via) the ordering (and nematic elasticity) of LCs,
      and (iii) the confinement of LCs leads to unanticipated size-dependent ordering
      (particularly in the context of LC emulsion droplets). The third and final
      advance addressed in this article involves interactions between colloids mediated
      by LCs. Recent experiments involving microparticles deposited at the LC-aqueous
      interface have revealed that LC-mediated interactions can drive interfacial
      assemblies of particles through reversible ordering transitions (e.g., from 1D
      chains to 2D arrays with local hexagonal symmetry). In addition, recent single
      nanoparticle measurements suggest that the ordering of LCs about nanoparticles
      differs substantially from micrometer-sized particles and that the interactions
      between nanoparticles mediated by the LCs are far weaker than predicted by theory
      (sufficiently weak that the interactions are reversible and thus enable self
      assembly). Finally, LC-mediated interactions between colloidal particles have
      also been shown to lead to the formation of colloid-in-LC gels that possess
      mechanical properties relevant to the design of materials that interface with
      living biological systems. Overall, these three topics serve to illustrate the
      broad opportunities that exist to do fundamental interfacial science and
      discovery-oriented research involving LCs.

PMID- 21090598
TI  - Controlling the properties of self-assembled monolayers by substrate curvature.
AB  - Properties of self-assembled monolayers (SAMs) can be tailored by the curvature
      of the underlying surface. This is so because on a curved support the density of
      SAM headgroups is always smaller than that of the surface-attachment sites. This
      density difference increases with increasing curvature and is most pronounced for
      SAMs formed on nanoscopic particles. This Perspective describes systems in which
      nanoscale curvature causes pronounced changes in the pK(a) of acid-presenting
      SAMs or in the electrochemical potential of redox-active molecules (including
      supramolecular "switches") attached to nanoparticles. It is suggested that in
      nanoparticles having regions of different curvature these geometrical differences
      can translate into site-selective charging; such "patchy" particles could be used
      as building blocks of pH-sensitive assemblies.

PMID- 21090599
TI  - Oxidative reactions of silicon atoms and clusters at ultralow temperature in
      helium droplets.
AB  - The reaction between Si and O(2) was studied in liquid He droplets at low
      temperature (T = 0.37 K) by monitoring the energy release during the reaction.
      Additionally, the reactions of Si atoms and clusters with the oxidation agents
      H(2)O and O(2) have been studied by mass spectrometry. It was found that Si atoms
      react fast with O(2) molecules. On the other hand, Si atoms and clusters do not
      react with H(2)O molecules. The energy released during the chemical reaction
      leads to the ejection of the products from small He droplets. In contrast, large
      He droplets (N(He) > 20000) are capable of keeping part of the reaction products
      in their interior. The observation of SiO(2) products with the mass spectrometer
      reveals that the He droplet can stabilize intermediate products in the exit
      channel.

PMID- 21090600
TI  - Ferrocene-bis(thymine/uracil) conjugates: base pairing directed, spacer dependent
      self-assembly and supramolecular packing.
AB  - X-ray crystallographic studies of methylene linked Ferrocene-bis(thymine/uracil)
      conjugates Fc(T:T)(M) and Fc(U:U)(M) reveal base dependent 2-D supramolecular
      assemblies generated via wobble self-pairing for bis-thymine and reverse wobble
      self-pairing for bis-uracil conjugates, differing in architecture from the
      corresponding butylene spacer linked conjugates.

PMID- 21090601
TI  - Effect of substitution on the optical properties and HOMO-LUMO gap of oligomeric
      paraphenylenes.
AB  - A series of dialkyl amino benzophenone dimers with various alkyl chain lengths is
      presented. Gaussian B3LYP/6-31G(d) calculations show that the band gap decreases
      within the dimer series as a function of the donor group efficiency. Theoretical
      calculations show that the interaction between phenyl-phenyl rings is more
      important than simple donor-acceptor effects. We report the experimental and
      electro-optical properties of one of these dimers, N,N-(dibutyl)-4-amino
      benzophenone. The experimental and theoretical results enabled us to design a new
      dimer. Altogether, side chain substituents reported herein tune the theoretical
      band gap of paraphenylene based dimers by over 8.86 eV.

PMID- 21090602
TI  - Characterization of lubrication oil emissions from aircraft engines.
AB  - In this first ever study, particulate matter (PM) emitted from the lubrication
      system overboard breather vent for two different models of aircraft engines has
      been systematically characterized. Lubrication oil was confirmed as the
      predominant component of the emitted particulate matter based upon the
      characteristic mass spectrum of the pure oil. Total particulate mass and size
      distributions of the emitted oil are also investigated by several high
      sensitivity aerosol characterization instruments. The emission index (EI) of
      lubrication oil at engine idle is in the range of 2-12 mg kg(-1) and increases
      with engine power. The chemical composition of the oil droplets is essentially
      independent of engine thrust, suggesting that engine oil does not undergo
      thermally driven chemical transformations during the ~4 h test window. Volumetric
      mean diameter is around 250-350 nm for all engine power conditions with a slight
      power dependence.

PMID- 21090603
TI  - Phosphorus transformations during decomposition of wetland macrophytes.
AB  - The microbially mediated transformation of detrital P entering wetlands has
      important implications for the cycling and long-term sequestration of P in
      wetland soils. We investigated changes in P forms in sawgrass (Cladium jamaicense
      Crantz) and cattail (Typha domingensis Pers.) leaf litter during 15 months of
      decomposition at two sites of markedly different nutrient status within a hard
      water subtropical wetland (Water Conservation Area 2A, Florida). Leaf litter
      decomposition at the nutrient enriched site resulted in net sequestration of P
      from the environment in forms characteristic of microbial cells (i.e.,
      phosphodiesters and pyrophosphate). In contrast, low P concentrations at the
      unenriched site resulted in little or no net sequestration of P, with changes in
      P forms limited to the loss of compounds present in the initial leaf litter. We
      conclude that under nutrient-rich conditions, P sequestration occurs through the
      accumulation of microbially derived compounds and the presumed concentration of
      endogenous macrophyte P. Under nutrient-poor conditions, standing P pools within
      wetland soils appear to be independent of the heterotrophic decomposition of
      macrophyte leaf litter. These conclusions have important implications for our
      ability to predict the nature, stability, and rates of P sequestration in
      wetlands in response to changes in nutrient loading.

PMID- 21090604
TI  - Heavy metal removal from shooting range soil by hybrid electrokinetics with
      bacteria and enhancing agents.
AB  - This study presents a method for heavy metal removal from a shooting range soil
      by a newly suggested hybrid technology. Active bioaugmentation was performed
      using Acidithiobacillus thiooxidans in the bioleaching step, and each test was
      sequentially combined with acid-enhanced and EDTA-enhanced electrokinetics. The
      results of the bioleaching processes indicated that S-oxidizing bacteria enhanced
      the mobility of heavy metals in the soil, based on their chemical forms. This
      process improved the final removal efficiencies of Cu and Zn in the hybrid
      electrokinetics. In the case of Pb, however, anglesite (PbSO(4)) has been easily
      formed in the bioleaching step from sulfate, a byproduct of S oxidation. Despite
      the potential negative effect on combining acid-enhanced electrokinetics, this
      problem was overcome by the application of an electrokinetic EDTA injection.
      Moreover, this method showed enhanced removal efficiency for Pb (92.7%) that was
      superior to that of an abiotic process. This hybrid method of EDTA-enhanced
      bioelectrokinetics demonstrated an adequate removal efficiency of heavy metals,
      especially Pb, with lower power consumption and eco-friendly soil conditions.

PMID- 21090605
TI  - Evaluation of hydraulic efficiency of disinfection systems based on residence
      time distribution curves.
AB  - Hydraulic efficiency is a vital component in evaluating the disinfection
      capability of a contact system. Current practice evaluates these systems based
      upon the theoretical detention time (TDT) and the rising limb of the residence
      time distribution (RTD) curve. This evaluation methodology is expected because
      most systems are built based on TDT under a "black-box" approach to disinfection
      system design. Within recent years, the proliferation of computational fluid
      dynamics (CFD) has allowed a more insightful approach to disinfection system
      design and analysis. Research presented in this study using CFD models and
      physical tracer studies shows that evaluation methods based upon TDT tend to
      overestimate, severely in some instances, the actual hydraulic efficiency as
      obtained from the system's flow and scalar transport dynamics and subsequent RTD
      curve. The main objective of this study was to analyze an alternative measure of
      hydraulic efficiency, the ratio t(10)/t(90), where t(10) and t(90) are the time
      taken for 10 and 90% of the input concentration to be observed at the outlet of a
      system, respectively, for various disinfection systems, primarily a pipe loop
      system, pressurized tank system, and baffled tank system, from their respective
      RTD curves and compare the results to the current evaluation method.

PMID- 21090606
TI  - Perchlorate, nitrate, and iodide intake through tap water.
AB  - Perchlorate is ubiquitous in the environment, leading to human exposure and
      potential impact on thyroid function. Nitrate can also competitively inhibit
      iodide uptake at the sodium-iodide symporter and thus reduce thyroid hormone
      production. This study investigates the intake of perchlorate, nitrate, and
      iodide attributable to direct and indirect tap water consumption. The National
      Health and Nutrition Examination Survey collected tap water samples and
      consumption data from 3262 U.S. residents during the years 2005-2006. The median
      perchlorate, nitrate, and iodide levels measured in tap water were 1.16, 758, and
      4.55 MUg/L, respectively. Measured perchlorate levels were below the United
      States Environmental Protection Agency (U.S. EPA) drinking water equivalent level
      for perchlorate (24.5 MUg/L). Significant correlations were found between iodide
      and nitrate levels (r = 0.17, p < 0.0001) and perchlorate and nitrate levels (r =
      0.25, p < 0.0001). On the basis of 24 h recall, 47% of the study participants
      reported drinking tap water; 89% reported either direct or indirect consumption
      of tap water. For the adult population (age >= 20 yrs) the median tap water
      consumption rate was 11.6 mL/kg-day. Using individual tap water consumption data
      and body weight, we estimated the median perchlorate, nitrate, and iodide dose
      attributable to tap water as 9.11, 11300, and 43.3 ng/kg-day, respectively, for
      U.S. adults. This perchlorate exposure dose from tap water is relatively small
      compared to the total perchlorate exposure dose previously characterized for the
      U.S. adults (median 64 ng/kg-day) and the U.S. EPA reference dose (700 ng/kg
      day).

PMID- 21090607
TI  - Are patients with potential celiac disease really potential? The answer of
      metabonomics.
AB  - Celiac disease (CD) is an autoimmune disorder caused by a permanent sensitivity
      to gluten in genetically susceptible individuals. Accurate diagnosis of CD at an
      early stage and its treatment with a gluten-free diet (GFD) are important for
      optimum treatment and prognosis. Recently, by employing a noninvasive metabonomic
      approach, we have shown that CD has a well-defined metabonomic signature. Here we
      address potential CD patients, defined as subjects who do not have, and have
      never had, a jejunal biopsy consistent with clear CD, and yet have immunological
      abnormalities similar to those found in celiac patients. Sixty-one overt CD
      patients at diagnosis, 29 patients with potential CD, and 51 control subjects
      were examined by (1)H NMR of their serum and urine: out of 29 potential CD
      patients, 24 were classified as CD and 5 as control subjects. Potential CD
      largely shares the metabonomic signature of overt CD. Most metabolites found to
      be significantly different between control and CD subjects were also altered in
      potential CD. Our results demonstrate that metabolic alterations may precede the
      development of small intestinal villous atrophy and provide a further rationale
      for early institution of GFD in patients with potential CD, as recently suggested
      by prospective clinical studies.

PMID- 21090608
TI  - Femtosecond dynamics of a porphyrin derivative confined by the human serum
      albumin protein.
AB  - The relaxation dynamics of 5,10,15,20-tetrakis(4-hydroxyphenyl)-porphyrin (p
      THPP) in tetrahydrofuran (THF) and encapsulated within the human serum albumin
      (HSA) protein in water solution was investigated. The protein environment affects
      the B->Q(y) and Q(x)->Q(y) transition dynamics (from 80 and 140-200 fs in THF to
      50 and 100 fs in HSA, respectively) as well as the lifetime of the relaxed Q(x)
      state (9.1 vs 9.9 ns). The most prominent differences are observed in the
      relaxation dynamics in the hot Q(x) state in HSA, which includes the energy
      transfer to the protein in ~1 ps and much slower solvent-assisted thermal
      equilibration component of about 20-30 ps.

PMID- 21090609
TI  - Characterizing the strength of individual hydrogen bonds in DNA base pairs.
AB  - The energies of individual hydrogen bonds (H-bonds) in A-T and G-C Watson-Crick
      base pairs were calculated according to the natural bond orbital (NBO) analysis
      of intermolecular interactions. The extent to which individual H-bonds are
      helpful in holding the two base pairs together was previously investigated
      quantitatively by a few different approaches, and the results of the present and
      previous estimations were compared. The method was validated by the determination
      of the H-bond strength changes in A-T and G-C pairs upon the substitution of the
      monomer (base) by two cationic substituents; the systems for which the changes
      were previously anticipated based on the modifications of the H-bonds' distances.

PMID- 21090610
TI  - Toward an understanding of the aqueous solubility of amino acids in the presence
      of salts: a molecular dynamics simulation study.
AB  - Ion-specific effects on the aqueous solubilities of biomolecules are relevant in
      many areas of biochemistry and life sciences. However, a general and well
      supported molecular picture of the phenomena has not yet been established. In
      order to contribute to the understanding of the molecular-level interactions
      governing the behavior of biocompounds in aqueous saline environments, classical
      molecular dynamics simulations were performed for aqueous solutions of four amino
      acids (alanine, valine, isoleucine, and 2-aminodecanoic acid), taken as model
      systems, in the presence of a series of inorganic salts. The MD results reported
      here provide support for a molecular picture of the salting-in/salting-out
      mechanism based on the presence/absence of interactions between the anions and
      the nonpolar moieties of the amino acids. These results are in good qualitative
      agreement with experimental solubilities and allow for a theoretical
      interpretation of the available data.

PMID- 21090611
TI  - Sol-gel synthesis, electrochemical characterization, and stability testing of
      Ti(0.7)W(0.3)O2 nanoparticles for catalyst support applications in proton
      exchange membrane fuel cells.
AB  - The materials currently used in proton-exchange membrane fuel cells (PEMFCs)
      require complex control of operating conditions to make them sufficiently durable
      to permit commercial deployment. One of the major materials challenges to allow
      simplification of fuel cell operating strategies is the discovery of catalyst
      supports that are much more stable to oxidative decomposition than currently used
      carbon blacks. Here we report the synthesis and characterization of
      Ti(0.7)W(0.3)O2 nanoparticles (approximately 50 nm diameter), a promising doped
      metal oxide that is a candidate for such a durable catalyst support. The
      synthesized nanoparticles were platinized, characterized by electrochemical
      testing, and evaluated for stability under PEMFC and other oxidizing acidic
      conditions. Ti(0.7)W(0.3)O2 nanoparticles show no evidence of decomposition when
      heated in a Nafion solution for 3 weeks at 80  degrees C. In contrast, when
      heated in sulfuric, nitric, perchloric, or hydrochloric acid, the oxide reacts to
      form salts such as titanylsulfatehydrate from sulfuric acid. Electrochemical
      tests show that rates of hydrogen oxidation and oxygen reduction by platinum
      nanoparticles supported on Ti(0.7)W(0.3)O2 are comparable to those of commercial
      Pt on carbon black.

PMID- 21090612
TI  - Thermodynamics of fatty acid degradation.
AB  - In this communication, the correlation of some thermodynamic properties of
      structurally similar biological compounds with items such as the number of carbon
      atoms or the number of its characteristic groups, such as phosphates, was applied
      to enzyme thermodynamics, to advance the thermodynamics of fatty acid
      degradation. It was shown that these concepts apply equally well for all three
      major thermodynamic functions: Gibbs energy of formation, enthalpy of formation,
      and entropy of formation. First, the standard transformed Gibbs energies of
      formation, Delta(f)G'(o), were calculated for the major portion of saturated
      fatty acids at 25  degrees C and pH 5, pH 7, and pH 9. Second, a total ATP yield
      was calculated for complete combustion of major saturated fatty acids to CO(2)
      and water. Third, the standard transformed Gibbs energies of reaction,
      Delta(r)G'(o), were calculated for enzyme reactions catalyzing complete beta
      oxidation of butyryl-CoA to acetyl-CoA at 25  degrees C and pH 7.

PMID- 21090614
TI  - Chain length effect on the binding of amphiphiles to serum albumin and to POPC
      bilayers.
AB  - The interaction of small molecules, such as drugs or metabolites, with proteins
      and biomembranes is of fundamental importance for their bioavailability. The
      systematic characterization of the binding affinity for structurally related
      ligands may provide rules that allow its prediction for any other relevant
      molecule. In this work we have studied a homologous series of fluorescent fatty
      amines with the fluorescent moiety 7-nitrobenz-2-oxa-1,3-diazol-4-yl covalently
      bound to the amine group (NBD-C(n); n = 4, 6, 8, 10, 12, 14, and 16) in aqueous
      solution and associated with BSA or lipid bilayers. We have found a linear
      dependence with the length of the alkyl chain, up to NBD-C(10), for the Gibb's
      free energy of partition between the aqueous solution and 1-palmitoyl-2-oleoyl
      phosphatidylcholine bilayers equal to DeltaDeltaG = -2.5 +/- 0.3 kJ/mol per
      methylene group. Additionally, the amphiphiles interacted efficiently with bovine
      serum albumin, and it was inhibited by fatty acids indicating that binding occurs
      to the fatty acids highest affinity binding site. The association of the
      amphiphiles with BSA and POPC bilayers was performed at different temperatures
      (15-35  degrees C) allowing for the calculation of the enthalpic and entropic
      contributions. A value of DeltaH = -15 +/- 4 kJ/mol was obtained for all
      amphiphiles and binding agents. The entropy contribution was always positive and
      increased with the length of the alkyl chain. The location of the ligand in the
      biological membrane is also of high relevance, namely because this will determine
      its effect on biomembrane properties at high ligand concentrations. With this
      goal, we have measured some photophysical properties of the amphiphiles inserted
      in POPC bilayers, and we found no significant variation along the series,
      indicating that the NBD group is located in a region with similar properties
      regardless of the length of the nonpolar group. An exception was noted for the
      case of NBD-C(14) whose parameters were somewhat different from the trend
      observed.

PMID- 21090613
TI  - Tyrosine-lipid peroxide adducts from radical termination: para coupling and
      intramolecular Diels-Alder cyclization.
AB  - Free radical co-oxidation of polyunsaturated lipids with tyrosine or phenolic
      analogues of tyrosine gave rise to lipid peroxide-tyrosine (phenol) adducts in
      both aqueous micellar and organic solutions. The novel adducts were isolated and
      characterized by 1D and 2D NMR spectroscopy as well as by mass spectrometry (MS).
      The spectral data suggest that the polyunsaturated lipid peroxyl radicals give
      stable peroxide coupling products exclusively at the para position of the tyrosyl
      (phenoxy) radicals. These adducts have characteristic (13)C chemical shifts at
      185 ppm due to the cross-conjugated carbonyl of the phenol-derived
      cyclohexadienone. The primary peroxide adducts subsequently undergo
      intramolecular Diels-Alder (IMDA) cyclization, affording a number of
      diastereomeric tricyclic adducts that have characteristic carbonyl (13)C chemical
      shifts at ~198 ppm. All of the NMR HMBC and HSQC correlations support the
      structure assignments of the primary and Diels-Alder adducts, as does MS
      collision-induced dissociation data. Kinetic rate constants and activation
      parameters for the IMDA reaction were determined, and the primary adducts were
      reduced with cuprous ion to give a phenol-derived 4-hydroxycyclohexa-2,5-dienone.
      No products from adduction of peroxyls at the phenolic ortho position were found
      in either the primary or cuprous reduction product mixtures. These studies
      provide a framework for understanding the nature of lipid-protein adducts formed
      by peroxyl-tyrosyl radical-radical termination processes. Coupling of lipid
      peroxyl radicals with tyrosyl radicals leads to cyclohexenone and
      cyclohexadienone adducts, which are of interest in and of themselves since, as
      electrophiles, they are likely targets for protein nucleophiles. One consequence
      of lipid peroxyl reactions with tyrosyls may therefore be protein-protein cross
      links via interprotein Michael adducts.

PMID- 21090616
TI  - Specific features of the dielectric continuum solvation model with a position
      dependent permittivity function.
AB  - We consider a modified formulation for the recently developed new approach in the
      continuum solvation theory (Basilevsky, M. V.; Grigoriev, F. V.; Nikitina, E. A.;
      Leszczynski, J. J. Phys. Chem. B 2010, 114, 2457) which is based on the exact
      solution of the electrostatic Poisson equation with the space-dependent
      dielectric permittivity. Its present modification ensures the property curl E = 0
      for the electric strength field E inherent to this solution, which is the
      obligatory condition imposed by Maxwell equations. The illustrative computation
      is made for the model system of the point dipole immersed in a spherical cavity
      of excluded volume.

PMID- 21090615
TI  - Conformational remodeling of femtomolar inhibitor-acetylcholinesterase complexes
      in the crystalline state.
AB  - The active center of acetylcholinesterase (AChE), a target site for competitive
      inhibitors, resides centrosymmetric to the subunit at the base of a deep, narrow
      gorge lined by aromatic residues. At the gorge entry, a peripheral site
      encompasses overlapping binding loci for noncompetitive inhibitors, which alter
      substrate access to the gorge. The click-chemistry inhibitor TZ2PA6 links the
      active center ligand, tacrine, to the peripheral site ligand, propidium, through
      a biorthogonal reaction of an acetylene and an azide that forms either a syn1 or
      an anti1 triazole. Compared with wild-type mouse AChE, a Tyr337Ala mutant
      displays full catalytic activity, albeit with 2-3 orders of magnitude higher
      affinities for the TZ2PA6 syn1 and anti1 regioisomers, reflected in low
      femtomolar K(d) values, diffusion-limited association, and dissociation half
      times greater than 1 month and 1 week, respectively. Three structures of each of
      the co-crystallized syn1 and anti1 complexes of the Tyr337Ala mutant were solved
      at three distinct times of crystal maturation, consistent with or exceeding the
      half-lives of the complexes in solution, while crystalline complexes obtained
      from soaked Tyr337Ala crystals led to picturing "freshly formed" complexes. The
      structures, at 2.55-2.75 A resolution, reveal a range of unprecedented
      conformations of the bound regioisomers, not observed in the wild-type AChE
      complexes, associated with concerted positional rearrangements of side chains in
      the enzyme gorge. Moreover, time-dependent conformational remodeling of the
      crystalline complexes appears to correlate with the dissociation half-times of
      the solution complexes. Hence, for the tight-binding TZ2PA6 inhibitors, the
      initial complexes kinetically driven in solution slowly form more stable
      complexes governed by thermodynamic equilibrium and observable in mature
      crystals.

PMID- 21090617
TI  - Spiky gold nanoshells.
AB  - We report a high-yield synthetic method for a new type of metal nanostructure,
      spiky gold nanoshells, which combine the morphological characteristics of hollow
      metal nanoshells and nanorods. Our method utilizes block copolymer assemblies and
      polymer beads as templates for the growth of spiky nanoshells. Various shapes of
      spiky metal nanoshells were prepared in addition to spherical nanoshells by using
      block copolymer assemblies such as rod-like micelles, vesicles, and bilayers as
      templates. Furthermore, spiky gold shells encapsulating magnetic nanoparticles or
      quantum dots were prepared based on the ability of block copolymers to self
      assemble with various types of nanoparticles and molecules. The capability to
      encapsulate other materials in the core, the shape tunability, and the highly
      structured surface of spiky nanoshells should benefit a range of imaging,
      sensing, and medical applications of metal nanostructures.

PMID- 21090618
TI  - Neutralizing positive charges at the surface of a protein lowers its rate of
      amide hydrogen exchange without altering its structure or increasing its
      thermostability.
AB  - This paper combines two techniques--mass spectrometry and protein charge ladders-
      to examine the relationship between the surface charge and hydrophobicity of a
      representative globular protein (bovine carbonic anhydrase II; BCA II) and its
      rate of amide hydrogen-deuterium (H/D) exchange. Mass spectrometric analysis
      indicated that the sequential acetylation of surface lysine-epsilon-NH3(+) groups
      -a type of modification that increases the net negative charge and hydrophobicity
      of the surface of BCA II without affecting its secondary or tertiary structure-
      resulted in a linear decrease in the aggregate rate of amide H/D exchange at pD
      7.4, 15  degrees C. According to analysis with MS, the acetylation of each
      additional lysine generated between 1.4 and 0.9 additional hydrogens that are
      protected from H/D exchange during the 2 h exchange experiment at 15  degrees C,
      pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which
      became protected upon acetylation were located on the side chain of the
      acetylated lysine residues (i.e., lys-epsilon-NHCOCH3) but were instead located
      on amide NHCO moieties in the backbone. The decrease in rate of exchange
      associated with acetylation paralleled a decrease in thermostability: the most
      slowly exchanging rungs of the charge ladder were the least thermostable (as
      measured by differential scanning calorimetry). This observation--that faster
      rates of exchange are associated with slower rates of denaturation--is contrary
      to the usual assumptions in protein chemistry. The fact that the rates of H/D
      exchange were similar for perbutyrated BCA II (e.g., [lys-epsilon
      NHCO(CH2)2CH3]18) and peracetylated BCA II (e.g., [lys-epsilon-NHCOCH3]18)
      suggests that the electrostatic charge is more important than the hydrophobicity
      of surface groups in determining the rate of H/D exchange. These electrostatic
      effects on the kinetics of H/D exchange could complicate (or aid) the
      interpretation of experiments in which H/D exchange methods are used to probe the
      structural effects of non-isoelectric perturbations to proteins (i.e.,
      phosphorylation, acetylation, or the binding of the protein to an oligonucleotide
      or to another charged ligand or protein).

PMID- 21090620
TI  - Water is the key to nonclassical nucleation of amorphous calcium carbonate.
AB  - Calcium carbonate is a ubiquitous mineral that represents one of the most
      significant biominerals, a major contributor to carbon sequestration through
      geological deposits, and a technological hindrance as a result of scale
      formation. Amorphous calcium carbonate is intimately involved in the nucleation
      and growth of this material, yet much remains undiscovered regarding the atomic
      detail. Through dynamical simulation we demonstrate that nucleation of amorphous
      calcium carbonate follows a nonclassical pathway. This arises from the addition
      of ion pairs to clusters exhibiting a consistently exothermic free energy that
      persists with increasing particle size. Furthermore, the disruption of the
      surrounding water of solvation by the atomically rough surface reduces the
      barrier to growth to the order of ambient thermal energy, thereby allowing the
      amorphous phase to grow faster than crystalline polymorphs. Amorphous calcium
      carbonate nanoparticles are also found to exploit size-dependent water content to
      render itself more stable than the favored bulk phase, calcite, below a critical
      diameter of close to 4 nm.

PMID- 21090619
TI  - Analysis of polar lipids in the serum from rats fed shiitake by liquid
      chromatography-mass spectrometry/mass spectrometry.
AB  - Consumption of a shiitake mushroom diet has been reported to have effects on
      serum phospholipids. However, much less is known about the effect on serum polar
      lipids including lysophospholipids and free fatty acids. In the present study,
      the effects of a shiitake diet were evaluated on the basis of identification and
      quantification of individual polar lipid components in rat serum using liquid
      chromatography-mass spectrometry/mass spectrometry. By comparison with standards
      and published data, 50 lysophospholipids and 32 free fatty acids were identified,
      and the concentrations of 27 polar lipids in rat serum were determined. Shiitake
      diets decreased the levels of all individual polar lipid components in the serum
      of male rat. The total level of serum polar lipids in males fed 4% shiitake diets
      (1365.71 mol/L) was significantly lower than that of the control (2270.26 mol/L).
      However, shiitake diets did not significantly affect the levels of serum polar
      lipids in female rats.

PMID- 21090621
TI  - Variation and correlation analysis of flavonoids and carotenoids in Korean
      pigmented rice (Oryza sativa L.) cultivars.
AB  - Flavonoids and carotenoids of pigmented rice ( Oryza sativa L.), including five
      black cultivars and two red cultivars, from Korea were characterized to determine
      the diversity among the phytochemicals and to analyze the relationships among
      their contents. Black cultivars were higher in flavonoids and carotenoids than
      the red and white cultivars. The profiles of eight phytochemicals identified from
      the rice grains were subjected to principal component analysis (PCA) to evaluate
      the differences among cultivars. PCA could fully distinguish between these
      cultivars. The Heugjinjubyeo (BR-1) and Heugseolbyeo (BR-2) cultivars were
      separated from the others based on flavonoid and carotenoid concentrations.
      Flavonoid contents had a positive correlation with carotenoid contents among all
      rice grains. The BR-1 and BR-2 cultivars appear to be good candidates for future
      breeding programs because they have simultaneously high flavonoid and carotenoid
      contents.

PMID- 21090623
TI  - Chiral poly(fluorene-alt-benzothiadiazole) (PFBT) and nanocomposites with gold
      nanoparticles: plasmonically and structurally enhanced chirality.
AB  - Materials with large chiral optical activity at visible wavelengths are of great
      interest in photonics, particularly as a route to chiral optical metamaterials.
      Here, we demonstrate the plasmonic enhancement of the chiral optical activity of
      chiral poly(fluorene-alt-benzothiadiazole) (PFBT) doped with gold nanoparticles.
      The supramolecular helical organization of polymeric chains with simultaneous
      dipole-dipole interaction of the helically ordered nanoparticles with the polymer
      and one another results in unprecedented values of chirality parameter (kappa
      ~0.02) at visible wavelengths in thin films.

PMID- 21090622
TI  - Mung bean trypsin inhibitor is effective in suppressing the degradation of
      myofibrillar proteins in the skeletal muscle of blue scad (Decapterus maruadsi).
AB  - Mung bean trypsin inhibitor (MBTI) of the Bowman-Birk family was purified to
      homogeneity with a molecular mass of approximately 9 kDa on tricine-sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 8887.25 Da as
      determined by matrix-assisted laser desorption/ionization-quadrupole ion trap
      time-of-flight mass spectrometry (MALDI-QIT-TOF MS). Using blue scad myofibrillar
      proteins as targets, it was found that, in the absence of MBTI, proteolysis of
      myofibrillar proteins, especially myosin heavy chain (MHC), could be identified
      after incubation at 55  degrees C for 2 h, while in the presence of MBTI, with a
      final concentration of 25 ng/mL, proteolysis of these proteins was greatly
      suppressed even after incubation for 3 h. Although cysteine proteinase inhibitor
      E-64 was also effective in preventing protein degradation, inhibitors for metallo
      and asparatic proteinases did not reveal obvious inhibitory effects. Our present
      results strongly suggested that the naturally occurring legume bean seed protein
      MBTI can be used as an effective additive in preventing marine fish blue scad
      surimi gel softening, which is quite possibly caused by myofibril-bound serine
      proteinase (MBSP).

PMID- 21090624
TI  - Molecular dials: hindered rotations in mono- and diferrocenyl anthracenes and
      triptycenes.
AB  - The syntheses, X-ray crystal structures, and molecular dynamics of 9
      ferrocenylanthracene, 3, 9,10-diferrocenylanthracene, 4, 9-ferrocenyltriptycene,
      7, and 9,10-diferrocenyltriptycene, 8, are reported. At 193 K, 3 exhibits C(s)
      symmetry via oscillation of the ferrocenyl only about the anthracene plane; at
      higher temperatures, complete rotation about the C(9)-ferrocenyl linkage becomes
      evident with a barrier of 10.6 kcal mol(-1). At 193 K, the ferrocenyls in 4 give
      rise to syn (C(2v)) and anti (C(2h)) rotamers that also interconvert at room
      temperature. In the corresponding triptycyl systems, 7 and 8, these rotational
      barriers increase to 17 kcal mol(-1); 9,10-diferrocenyltriptycene exists as
      slowly interconverting meso and racemic rotamers, in which the ferrocenyl
      moieties are, respectively, eclipsed (C(2v)) or staggered (C2). 2D-EXSY NMR data
      recorded with different mixing times indicate clearly that these interconversions
      proceed in a stepwise manner, for example, rac->meso->rac, thus behaving as a set
      of molecular dials.

PMID- 21090625
TI  - Uncovering the mechanistic role of HMPA in the samarium Barbier reaction.
AB  - The presence of HMPA is critical for the selective coupling of alkyl halides and
      ketones by SmI2. Although previous rate studies have shown that HMPA dramatically
      accelerates the reduction of alkyl halides over ketones, the basis of this rate
      acceleration is unknown. In this communication, we report experimental and
      computational evidence that demonstrate that the selectivity observed in the
      samarium Barbier reaction is in part a result of activation of the alkyl halide
      bond by HMPA.

PMID- 21090626
TI  - Insights into metal borohydride and aluminohydride bonding: X-ray and neutron
      diffraction structures and a DFT and charge density study of [Na(15-crown
      5)][EH(4)] (E = B, Al).
AB  - The neutron and X-ray structures of [Na(15-crown-5)][BH(4)] and [Na(15-crown
      5)][AlH(4)], respectively, are reported, along with a topological analysis of
      their DFT-computed charge densities that explores the bonding between the anionic
      complex hydride [EH(4)](-) (E = B, Al) and the counterion [Na(15-crown-5)](+). In
      each case, the interaction is weak and mainly electrostatic in nature; however,
      notable differences are observed in the manner in which [BH(4)](-) and [AlH(4)](
      ) bind to the metal, which explains their different coordination modes. A range
      of unconventional E-H...H-C contacts is revealed to play an important role in the
      overall bonding and crystal packing of both complexes. These interactions can be
      classified as weak dihydrogen bonds based on the atoms in molecules approach.

PMID- 21090627
TI  - Influence of the synthetic conditions on the structural diversity of extended
      manganese-oxalato-1,2-bis(4-pyridyl)ethylene systems.
AB  - We report herein the synthesis and physicochemical characterization of eight new
      manganese-oxalato compounds with 1,2-bis(4-pyridyl)ethylene (bpe):
      {(Hbpe)(2)[Mn(2)(MU-ox)(3)].~0.8(C(2)H(5)OH).~0.4(H(2)O)}(n) (1), {[Mn(MU-ox)(MU
      bpe)].xH(2)O}(n) (2), [Mn(2)(MU-ox)(2)(MU-bpe)(bpe)(2)](n) (3), [Mn(MU-ox)(MU
      bpe)](n) (4a and 4b), and {[Mn(4)(MU-ox)(3)(MU-bpe)(4)(H(2)O)(4)].(X)(2).mY}(n)
      with X = NO(3)(-) (5a), Br(-) (5b), and ClO(4)(-) (5c) and Y = solvation
      molecules. The appropriate selection of the synthetic conditions allowed us to
      control the crystal structure and to design extended 2D and 3D frameworks.
      Compound 1 is obtained at acid pH values and its crystal structure consists of
      stacked [Mn(2)(MU-ox)(3)](2-) layers with cationic Hbpe(+) molecules intercalated
      among them. Compound 2 was obtained at basic pH values with a manganese/bpe ratio
      of 1:1, and the resulting 3D structure consists of an interpenetrating framework
      in which metal-oxalato chains are bridged by bpe ligands, leading to a
      microporous network that hosts a variable number of water molecules (between 0
      and 1) depending on the synthetic conditions. Compound 3, synthesized with a
      manganese/bpe ratio of 1:3, shows a 2D framework in which linear metal-oxalato
      chains are joined by bis-monodentate 1,2-bis(4-pyridyl)ethylene ligands. The
      thermal treatment of compound 3 permits the release of one of the bpe molecules,
      giving rise to two new 2D crystalline phases of formula [Mn(MU-ox)(MU-bpe)](n)
      (4a and 4b) depending on the heating rate. The open structures of 5a-5c were
      synthesized in a medium with a high concentration of nitrate, perchlorate, or
      bromide salts (potassium or sodium as cations). These anions behave as templating
      agents directing the crystal growing toward a cationic porous network, in which
      the anions placed in the voids and channels of the structure present high
      mobility, as inferred from the ionic exchange experiments. Variable-temperature
      magnetic susceptibility measurements show an overall antiferromagnetic behavior
      for all compounds, which are discussed in detail.

PMID- 21090628
TI  - Theoretical studies of salt-bridge formation by amino acid side chains in low and
      medium polarity environments.
AB  - Salt-bridge formation between Asp/Glu...Lys and Asp/Glu...Arg side chains has
      been studied by model systems including formic and acetic acids as proton donors
      and methylamine, guanidine, and methylguanidine as proton acceptors. Calculations
      have been performed up to the CCSD(T)(CBS)//MP2/aug-cc-pvtz level with formic
      acid proton donors. Complexes formed with acetic acid were studied at the
      CCSD(T)/aug-cc-pvdz//MP2/aug-cc-pvdz level. Protein environments of low and
      moderate polarity were mimicked by a continuum solvent with dielectric constants
      (epsilon) set to 5 and 15, respectively. Free energy differences, DeltaG(tot),
      were calculated for the neutral, hydrogen-bonded form and for the tautomeric ion
      pair. These values predict that a salt bridge is not favored for the
      Asp/Glu...Lys pair, even in an environment with epsilon as large as 15. In
      contrast, the Asp/Glu...Arg salt bridge is feasible even in an environment with
      epsilon = 5. Charge transfers for the complexes were calculated on the basis of
      CHELPG and AIM charges.

PMID- 21090629
TI  - Multielectron redox reactions involving C-C coupling and cleavage in uranium
      Schiff base complexes.
AB  - The reaction of U(III) with Schiff base ligands and the reduction of U(IV) Schiff
      base complexes both promote C-C bond formation to afford dinuclear or mononuclear
      U(IV) amido complexes, which can release up to four electrons to substrates
      through the oxidative cleavage of the C-C bond.

PMID- 21090630
TI  - Two-coordinate first row transition metal complexes with short unsupported metal
      metal bonds.
AB  - A series of first row transition metal complexes with unsupported M-Fe bonds,
      (3,5-(i)Pr2-Ar*)MFe(eta(5)-C5H5)(CO)2 (M = Fe (1), Mn (2), Cr (3), 3,5-(i)Pr2-Ar*
      = -C6H-2,6-(C6H2-2,4,6-(i)Pr3)2-3,5-(i)Pr2), was synthesized by salt metathesis.
      They were characterized by (1)H NMR, UV-vis spectroscopy, X-ray crystallography,
      and SQUID magnetic measurements. Two distinct Fe atoms in 1 were confirmed by
      Mossbauer spectroscopy. All three compounds feature short metal-metal bond
      distances (Fe-Fe, 2.3931(8) A (1); Mn-Fe, 2.4512(5) A (2); Cr-Fe, 2.4887(5) A
      (3)). Their DFT computed structures were in excellent agreement with the
      experimental data and revealed a dative bonding interaction between the metals.

PMID- 21090631
TI  - Surface plasmon resonance biosensor for rapid label-free detection of
      microribonucleic acid at subfemtomole level.
AB  - Microribonucleic acids (miRNAs) have been linked with various regulatory
      functions and disorders, such as cancers and heart diseases. They, therefore,
      present an important target for detection technologies for future medical
      diagnostics. We report here a novel method for rapid and sensitive miRNA
      detection and quantitation using surface plasmon resonance (SPR) sensor
      technology and a DNA*RNA antibody-based assay. The approach takes advantage of a
      novel high-performance portable SPR sensor instrument for spectroscopy of surface
      plasmons based on a special diffraction grating called a surface plasmon coupler
      and disperser (SPRCD). The surface of the grating is functionalized with
      thiolated DNA oligonucleotides which specifically capture miRNA from a liquid
      sample without amplification. Subsequently, an antibody that recognizes DNA*RNA
      hybrids is introduced to bind to the DNA*RNA complex and enhance sensor response
      to the captured miRNA. This approach allows detection of miRNA in less than 30
      min at concentrations down to 2 pM with an absolute amount at high attomoles. The
      methodology is evaluated for analysis of miRNA from mouse liver tissues and is
      found to yield results which agree well with those provided by the quantitative
      polymerase chain reaction (qPCR).

PMID- 21090632
TI  - Selective synthesis of 7-substituted purines via 7,8-dihydropurines.
AB  - A simple and efficient protocol for the preparation of 7-substituted purines is
      described. 6- and 2,6-Dihalopurines were N(9)-tritylated and then transformed to
      7,8-dihydropurines by DIBAL-H. Subsequent N(7)-alkylation followed by N(9)-trityl
      deprotection with trifluoroacetic acid was accompanied by spontaneous
      reoxidation, which led to the 7-substituted purines at 55-88% overall isolated
      yields.

PMID- 21090633
TI  - Electrochemical detection of peroxynitrite using a biosensor based on a
      conducting polymer-manganese ion complex.
AB  - A peroxynitrite (ONOO(-)) biosensor has been developed through the preparation of
      a new manganese-[poly-2,5-di-(2-thienyl)-1H-pyrrole)-1-(p-benzoic acid)] (Mn
      pDPB) complex. DPB monomer was first synthesized and polymerized for the purpose
      of providing a polymer backbone for complex formation with Mn(2+) ion. The Mn
      pDPB complex was characterized via Magnetomotive Force (MMF) simulation, X-ray
      photoelectron spectroscopy (XPS), and cyclic voltammetry. The complex selectively
      enhanced the reduction process of ONOO(-) which was used as the analytical signal
      for chronoamperometric detection. A polyethyleneimmine (PEI) layer was coated on
      the complex surface to increase selectivity and stability. The chronoamperometric
      calibration plot showed the hydrodynamic range of 2.0 * 10(-8)-5.0 * 10(-7) M.
      The detection limit was determined to be 1.9 (+/-0.2) * 10(-9) M based on S/N =
      3. The microbiosensor, fabricated on a 100 MUm diameter Pt tip, was applied in a
      real rat plasma sample for the detection of spiked concentrations of ONOO(-). The
      reliability and long-term stability of the microbiosensor was also examined with
      YPEN-1 cells in vitro, and the results shown were promising.

PMID- 21090634
TI  - Field-flow fractionation: addressing the nano challenge.
AB  - Field-flow fractionation is coming of age as a family of analytical methods for
      separating and characterizing macromolecules, nanoparticles, and particulates.
      The capabilities and versatility of these techniques are discussed in light of
      the challenges that are being addressed in analyzing nanometer-sized sample
      components and the insights gained through their use in applications ranging from
      materials science to biology. (To listen to a podcast about this feature, please
      go to the Analytical Chemistry multimedia page at
      pubs.acs.org/page/ancham/audio/index.html .).

PMID- 21090635
TI  - High-throughput metabolic toxicity screening using magnetic biocolloid reactors
      and LC-MS/MS.
AB  - An inexpensive, high-throughput genotoxicity screening method was developed by
      using magnetic particles coated with cytosol/microsome/DNA films as biocolloid
      reactors in a 96-well plate format coupled with liquid chromatography-mass
      spectrometry. Incorporation of both microsomal and cytosolic enzymes in the films
      provides a broad spectrum of metabolic enzymes representing a range of metabolic
      pathways for bioactivation of chemicals. Reactive metabolites generated via this
      process are trapped by covalently binding to DNA in the film. The DNA is then
      hydrolyzed and nucleobase adducts are collected using filters in the bottom for
      the 96-well plate of analysis by capillary liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The magnetic particles facilitate simple and rapid
      sample preparation and workup. Major DNA adducts from ethylene dibromide, N
      acetyl-2-aminofluorene and styrene were identified in proof-of-concept studies.
      Relative formation rates of DNA adducts correlated well with rodent genotoxicity
      metric TD(50) for the three compounds. This method has the potential for high
      throughput genotoxicity screening, providing chemical structure information that
      is complementary to toxicity bioassays.

PMID- 21090636
TI  - Utilizing spectral counting to quantitatively characterize tandem removal of
      abundant proteins (TRAP) in human plasma.
AB  - Biomarker discovery efforts in serum and plasma are greatly hindered by the
      presence of high abundance proteins that prevent the detection and quantification
      of less abundant, yet biologically significant, proteins. The most common method
      for addressing this problem is to specifically remove the few abundant proteins
      through immunoaffinity depletion/subtraction. Herein, we improved upon this
      method by utilizing multiple depletion columns in series, so as to increase the
      efficiency of the abundant protein removal and augment the
      detection/identification of less abundant plasma proteins. Spectral counting was
      utilized to make quantitative comparisons between undepleted plasma, plasma
      depleted with a single depletion column, and plasma depleted using two or three
      depletion columns in tandem. In the undepleted plasma only 29 lower abundance
      protein groups were identified with the top-scoring protein from each group
      having a median spectral count of 3, while in the plasma processed using a single
      HSA depletion column 61 such protein groups were identified with a median
      spectral count of 8. In comparison, 76 lesser abundant protein groups were
      identified with a median spectral count of 11.5 in the two column setup (i.e.,
      HSA followed by MARS Hu14). However, in the ultimate depleted plasma sample,
      which was created using three depletion columns in tandem, the number of less
      abundant protein groups identified increase to 81 and the median spectral count
      for the top-scoring proteins from each group increased to 15 counts per protein.
      Moreover, exogenous B-type natriuretic peptide-32, which was added to the plasma
      as a detection benchmark at 12 MUg/mL, was only detected in the plasma sample
      depleted using three depletion columns in tandem. Collectively, these data
      demonstrate that this method, tandem removal of abundant proteins or TRAP,
      provides superior removal efficiency compared to traditional applications and
      improves the depth of proteome coverage in plasma.

PMID- 21090637
TI  - Biochemical thermodynamics and rapid-equilibrium enzyme kinetics.
AB  - Biochemical thermodynamics is based on the chemical thermodynamics of aqueous
      solutions, but it is quite different because pH is used as an independent
      variable. A transformed Gibbs energy G' is used, and that leads to transformed
      enthalpies H' and transformed entropies S'. Equilibrium constants for enzyme
      catalyzed reactions are referred to as apparent equilibrium constants K' to
      indicate that they are functions of pH in addition to temperature and ionic
      strength. Despite this, the most useful way to store basic thermodynamic data on
      enzyme-catalyzed reactions is to give standard Gibbs energies of formation,
      standard enthalpies of formation, electric charges, and numbers of hydrogen atoms
      in species of biochemical reactants like ATP. This makes it possible to calculate
      standard transformed Gibbs energies of formation, standard transformed enthalpies
      of formation of reactants (sums of species), and apparent equilibrium constants
      at desired temperatures, pHs, and ionic strengths. These calculations are
      complicated, and therefore, a mathematical application in a computer is needed.
      Rapid-equilibrium enzyme kinetics is based on biochemical thermodynamics because
      all reactions in the mechanism prior to the rate-determining reaction are at
      equilibrium. The expression for the equilibrium concentration of the enzyme
      substrate complex that yields products can be derived by applying Solve in a
      computer to the expressions for the equilibrium constants in the mechanism and
      the conservation equation for enzymatic sites. In 1979, Duggleby pointed out that
      the minimum number of velocities of enzyme-catalyzed reactions required to
      estimate the values of the kinetic parameters is equal to the number of kinetic
      parameters. Solve can be used to do this with steady-state rate equations as well
      as rapid-equilibrium rate equations, provided that the rate equation is a
      polynomial. Rapid-equilibrium rate equations can be derived for complicated
      mechanisms that involve several reactants and various types of inhibitors,
      activators, and moderators.

PMID- 21090638
TI  - Microstructure and hydrogen bonding in water-acetonitrile mixtures.
AB  - The connection of hydrogen bonding between water and acetonitrile in determining
      the microheterogeneity of the liquid mixture is examined using NPT molecular
      dynamics simulations. Mixtures for six, rigid, three-site models for acetonitrile
      and one water model (SPC/E) were simulated to determine the amount of water
      acetonitrile hydrogen bonding. Only one of the six acetonitrile models (TraPPE
      UA) was able to reproduce both the liquid density and the experimental estimates
      of hydrogen bonding derived from Raman scattering of the CN stretch band or from
      NMR quadrupole relaxation measurements. A simple modification of the acetonitrile
      model parameters for the models that provided poor estimates produced hydrogen
      bonding results consistent with experiments for two of the models. Of these, only
      one of the modified models also accurately determined the density of the
      mixtures. The self-diffusion coefficient of liquid acetonitrile provided a final
      winnowing of the modified model and the successful, unmodified model. The
      unmodified model is provisionally recommended for simulations of water
      acetonitrile mixtures.

PMID- 21090639
TI  - Enhancement of ammonia dehydrogenation by introduction of oxygen onto cobalt and
      iron cluster cations.
AB  - Reactions of oxygen-chemisorbed cobalt and iron cluster cations (Co(n)O(m)(+) and
      Fe(n)O(m)(+); n = 3-6, m = 1-3) with an NH(3) molecule have been investigated in
      comparison with their bare metal cluster cations at a collision energy of 0.2 eV
      by use of a guided ion beam tandem mass spectrometer. We have observed three
      kinds of reaction products, which come from NH(3) chemisorption with and without
      release of a metal atom from the cluster and dehydrogenation of the chemisorbed
      NH(3). Reaction cross sections and branching fractions are strongly influenced by
      the number of oxygen atoms introduced onto the metal clusters. Oxygen-chemisorbed
      metal clusters with particular compositions such as Co(4)O(+), Co(5)O(2)(+), and
      Fe(5)O(2)(+) are extremely reactive for NH(3) dehydrogenation, whereas
      Co(4)O(2)(+) and Fe(4)O(2)(+) exhibit high reactivity for NH(3) chemisorption
      with metal release. The enhancement of dehydrogenation for specific compositions
      can be interpreted in terms of competition between O-H and neighboring Co-H (or
      Fe-H) formation.

PMID- 21090640
TI  - Naphthobipyrrole: versatile synthesis and electropolymerization.
AB  - A facile synthetic route to a new polycyclic pyrrole derivative, 3,8-diethyl-1,10
      dihydro-benzo[e]pyrrolo[3,2-g]indole (1), is reported. This annulated bipyrrole
      acts as a monomer for electropolymerization and forms an electrochromic
      conducting polymer (poly1) when electrooxidized at low potentials (0.4 V vs
      Ag/Ag(+)) in acetonitrile. The presence of alkyl substituents at the 3 and 8
      carbons (beta-pyrrolic positions) induces regioselective 2,5'-coupling of the
      pyrrole repeat units and gives rise to the more uniform polymeric product, poly1.
      Poly1 exhibits globular morphology, as judged from SEM pictures. Its
      spectroelectrochemical features can be attributed to the formation of four
      possible states: neutral, polaron, bipolaron, and transverse bipolaron. The
      relatively low switching potentials (-0.6 to +0.9 V vs Ag/Ag(+) in MeCN)
      displayed by poly1 leads us to suggest that 1 has a role to play as a
      polymerizable moiety for the development of multicolor electrochromic materials.

PMID- 21090641
TI  - ECHO-LNA conjugates: hybridization-sensitive fluorescence and its application to
      fluorescent detection of various RNA strands.
AB  - Hybridization-sensitive fluorescent DNA probes containing the nucleotide units of
      locked nucleic acid (LNA) have been developed. Exciton-controlled hybridization
      sensitive fluorescent oligonucleotide (ECHO) probes that incorporated LNA
      nucleotides achieved high thermostability of the hybrid with target RNA strands.
      The appropriately designed ECHO-LNA chimeric probes exhibited an effective on-off
      switching property of fluorescence depending on hybridization with RNA and
      facilitated fluorescent detection of the TAR RNA strand forming a hairpin
      structure and distinction of one base difference in PLAC4 RNA sequence.

PMID- 21090642
TI  - Functional cationic nanomagnet-porphyrin hybrids for the photoinactivation of
      microorganisms.
AB  - Cationic nanomagnet-porphyrin hybrids were synthesized and their photodynamic
      therapy capabilities were investigated against the Gram (-) Escherichia coli
      bacteria, the Gram (+) Enterococcus faecalis bacteria and T4-like phage. The
      synthesis, structural characterization, photophysical properties, and
      antimicrobial activity of these new materials are discussed. The results show
      that these new multicharged nanomagnet-porphyrin hybrids are very stable in water
      and highly effective in the photoinactivation of bacteria and phages. Their
      remarkable antimicrobial activity, associated with their easy recovery, just by
      applying a magnetic field, makes these materials novel photosensitizers for water
      or wastewater disinfection.

PMID- 21090643
TI  - A two-step, one-pot enzymatic synthesis of 2-substituted 1,3-diols.
AB  - A biocatalytic cascade reaction was designed for the stereoselective synthesis of
      optically pure 2-alkyl-1,3-diols employing two enzymes. The cascade process
      consists of two consecutive steps: a stereoselective diketone reduction and a
      hydroxy ketone reduction. Chiral diols were formed by the addition of
      ketoreductases in the same vessel, in high stereoselectivity and chemical yield,
      without the isolation of the intermediate beta-hydroxy ketones.

PMID- 21090644
TI  - Fabrication of 7.2% efficient CZTSSe solar cells using CZTS nanocrystals.
AB  - Earth abundant copper-zinc-tin-chalcogenide (CZTSSe) is an important class of
      material for the development of low cost and sustainable thin film solar cells.
      The fabrication of CZTSSe solar cells by selenization of CZTS nanocrystals is
      presented. By tuning the composition of the CZTS nanocrystals and developing a
      robust film coating method, a total area efficiency as high as 7.2% under AM 1.5
      illumination and light soaking has been achieved.

PMID- 21090645
TI  - Facile synthesis of Raman active phospholipid gold nanoparticles.
AB  - Gold nanoparticle-based surface-enhanced Raman scattering (SERS) probes have
      shown promise for disease detection and diagnosis. To improve their structural
      and functional stability for in vivo applications, we synthesized a colloidal
      SERS gold nanoparticle that encapsulates Raman molecules adsorbed on 60 nm gold
      with a nonthiol phospholipid coating. Transmission electron microscopy and Raman
      and UV spectroscopy validated its reproducibility and stability. This novel lipid
      based SERS probe provides a viable alternative to the PEGylation and silica
      coating strategies.

PMID- 21090646
TI  - Effect of collision energy optimization on the measurement of peptides by
      selected reaction monitoring (SRM) mass spectrometry.
AB  - Proteomics experiments based on Selected Reaction Monitoring (SRM, also referred
      to as Multiple Reaction Monitoring or MRM) are being used to target large numbers
      of protein candidates in complex mixtures. At present, instrument parameters are
      often optimized for each peptide, a time and resource intensive process. Large
      SRM experiments are greatly facilitated by having the ability to predict MS
      instrument parameters that work well with the broad diversity of peptides they
      target. For this reason, we investigated the impact of using simple linear
      equations to predict the collision energy (CE) on peptide signal intensity and
      compared it with the empirical optimization of the CE for each peptide and
      transition individually. Using optimized linear equations, the difference between
      predicted and empirically derived CE values was found to be an average gain of
      only 7.8% of total peak area. We also found that existing commonly used linear
      equations fall short of their potential, and should be recalculated for each
      charge state and when introducing new instrument platforms. We provide a fully
      automated pipeline for calculating these equations and individually optimizing CE
      of each transition on SRM instruments from Agilent, Applied Biosystems, Thermo
      Scientific and Waters in the open source Skyline software tool (
      http://proteome.gs.washington.edu/software/skyline ).

PMID- 21090647
TI  - Building addressable libraries: the use of "safety-catch" linkers on
      microelectrode arrays.
AB  - A "safety-catch" linker strategy has been used to site-selectively cleave and
      characterize molecules from a microelectrode array. The linkers are attached to
      the array by means of an ester and contain either a protected amine or protected
      alcohol nucleophile that can be released using acid generated at the
      microelectrodes.

PMID- 21090648
TI  - Concise synthesis of the Erythrina alkaloid 3-demethoxyerythratidinone via
      combined rhodium catalysis.
AB  - The total synthesis of the erythrina alkaloid 3-demethoxyerythratidinone has been
      achieved via a strategy based on combined rhodium catalysis. The catalytic tandem
      cyclization effected by the interplay of alkynyl and vinylidene rhodium species
      allows for efficient access to the A and B rings of the tetracyclic erythrinane
      skeleton in a single step. The synthesis also features rapid preparation of the
      requisite precursor for the double ring closure and thus has been completed in
      only 7 total steps in 41% overall yield.

PMID- 21090649
TI  - Characterization of heat-induced changes in skim milk using asymmetrical flow
      field-flow fractionation coupled with multiangle laser light scattering.
AB  - Separation and size measurement of protein particles are a relevant approach to
      monitor heat-induced changes in skim milk. Unfortunately, no method is currently
      available at low cost and without excessive preparation of the samples.
      Therefore, the present study aimed at evaluating the interest of asymmetrical
      flow field-flow fractionation (AFlFFF) coupled with multiangle laser light
      scattering (MALLS) for this purpose. Unheated and heated skim milk samples at pH
      6.5 and 7.2 were prepared and comparatively analyzed using AFlFFF-MALLS, size
      exclusion chromatography (SEC-MALLS) and dynamic light scattering. The results
      showed that AFlFFF could evidence the conversion of the native whey proteins of
      unheated milk into heat-induced whey protein/kappa-casein complexes in the serum
      phase of milk and possibly on the surface of the casein micelles. The pH-induced
      changes in the partition of the complexes between the serum and the micellar
      phases could also be observed. The results therefore showed the interest of
      AFlFFF-MALLS to monitor the heat-induced changes in particle sizes in skim milk
      and to separate the different protein components of unheated and heated skim
      milk.

PMID- 21090650
TI  - Comment on effect of heating on the stability of quinolones in milk.

PMID- 21090651
TI  - Discovery of non-glycoside sodium-dependent glucose co-transporter 2 (SGLT2)
      inhibitors by ligand-based virtual screening.
AB  - A ligand-based virtual screening strategy (a combination of pharmacophore model
      generation, shape-based scoring, and structure clustering analysis) was developed
      to discover novel SGLT2 inhibitors. The best pharmacophore model, generated from
      eight glycoside inhibitors, was utilized to virtually screen three chemical
      databases that led to the identification of three non-glycoside SGLT2 inhibitors.
      This is the first report of the generation of a pharmacophore model from
      glycosides that has then been used to discover novel non-glycosides hits.

PMID- 21090652
TI  - Concise formal total synthesis of platensimycin mediated by a stereoselective
      autoxidation and hydroxyl group directed conjugative reduction.
AB  - The synthesis of 13, an advanced intermediate in the Nicolaou synthesis of
      platensimycin 1, was made from 9 by autoxidation to give 10, which was
      stereoselectively reduced providing 12. Finally, dehydration of 12 by heating in
      DMSO resulted in 13.

PMID- 21090653
TI  - Combination of indene-C60 bis-adduct and cross-linked fullerene interlayer
      leading to highly efficient inverted polymer solar cells.
AB  - A poly(3-hexylthiophene) (P3HT)-based inverted solar cell using indene-C60 bis
      adduct (ICBA) as the acceptor achieved a high open-circuit voltage of 0.82 V due
      to ICBA's higher-lying lowest unoccupied molecular orbital level, leading to an
      exceptional power-conversion efficiency (PCE) of 4.8%. By incorporating a cross
      linked fullerene interlayer, C-PCBSD, to further modulate the interface
      characteristics, the ICBA:P3HT-based inverted device exhibited an improved short
      circuit current and fill factor, yielding a record high PCE of 6.2%.

PMID- 21090655
TI  - Parametrization and application of a coarse grained force field for
      benzene/fullerene interactions with lipids.
AB  - Recently, we reported new coarse grain (CG) force fields for lipids and
      phenyl/fullerene based molecules. Here, we developed the cross parameters
      necessary to unite those force fields and then applied the model to investigate
      the nature of benzene and C(60) interactions with lipid bilayers. The interaction
      parameters between the phenyl and lipid CG sites are based on experimental and
      all atom (AA) molecular dynamics (MD) data. The resulting force field was tested
      on benzene rich lipid bilayers and shown to reproduce general behavior expected
      from experiments. The parameters were then applied to C(60) interactions with
      lipid bilayers. Overall, the results showed excellent agreement with AA MD and
      experimental observations. In the C(60) lipid systems, the fullerenes were shown
      to aggregate even at the lowest concentrations investigated.

PMID- 21090654
TI  - Chiral Bronsted base-promoted nitroalkane alkylation: enantioselective synthesis
      of sec-alkyl-3-substituted indoles.
AB  - A Bronsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles
      provides indole heterocycles substituted at C3 bearing a sec-alkyl group with
      good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a
      product with equally high ee. An indolenine intermediate is implicated in the
      addition step, and surprisingly, water cosolvent was found to have a beneficial
      effect in this step, leading to a one-pot protocol for
      elimination/enantioselective addition using PBAM, a bis(amidine) chiral
      nonracemic base.

PMID- 21090656
TI  - Implementation of new TPD analysis techniques in the evaluation of second order
      desorption kinetics of cyanogen from Cu(001).
AB  - The interactions of cyanide species with a copper (001) surface were studied with
      temperature programmed desorption (TPD) and X-ray photoelectron spectroscopy
      (XPS). Adsorbed cyanide species (CN(a)) undergo recombinative desorption evolving
      molecular cyanogen (C(2)N(2)). As the adsorbed CN species charge upon adsorption,
      mutually repulsive dipolar interactions lead to a marked desorption energy
      reduction with increasing CN(a) coverages. Two new TPD analysis approaches were
      developed, which used only accurately discernible observables and which do not
      assume constant desorption energies, E(d), and pre-exponential values, nu. These
      two approaches demonstrated a linear variation of E(d) with instantaneous
      coverage. The first approach involved an analysis of the variations of desorption
      peak asymmetry with initial CN coverages. The second quantitative approach
      utilized only temperatures and intensities of TPD peaks, together with deduced
      surface coverages at the peak maxima, also as a function of initial surface
      coverages. Parameters derived from the latter approach were utilized as initial
      inputs for a comprehensive curve fit analysis technique. Excellent fits for all
      experimental desorption curves were produced in simulations. The curve fit
      analysis confirms that the activation energy of desorption of 170-180 kJ/mol at
      low coverage decreases by up to 14-15 kJ/mol at CN saturation.

PMID- 21090657
TI  - Co-cross-linking silk matrices with silica nanostructures for robust ultrathin
      nanocomposites.
AB  - We report on a novel assembly approach to fabricate ultrathin robust freely
      standing nanocomposite membranes. The materials are composed of a pre-cross
      linked silk fibroin matrix with incorporated silica nanoparticles with
      silsesquioxane cores (POSS) or clay nanoplatelets. These reinforced silk
      membranes have enhanced mechanical properties as compared to traditional silk
      based nanocomposites reported previously. Up to 6-fold and 8-fold increase in
      elastic modulus and toughness, respectively, were found for these nanocomposites.
      In contrast, traditional LbL-assembled nanocomposites showed only a 3-fold
      increase in mechanical strength. The silk nanocomposites obtained also revealed
      excellent optical transparency in the visible region especially if reinforced
      with POSS nanoparticles, which suggests their utility as low cost, nontoxic, and
      easily scalable reinforced biomaterials for mechanically demanding applications.

PMID- 21090658
TI  - Synthesis of magnetic/luminescent alginate-templated composite microparticles
      with temperature-dependent photoluminescence under high-frequency magnetic field.
AB  - Highly magnetic luminescent alginate-templated composite microparticles were
      successfully synthesized by a novel process combining emulsification and layer-by
      layer self-assembly techniques. The composite microparticles were characterized
      by zeta-potential analyzer, transmission electron microscope, X-ray diffraction,
      Fourier transform infrared spectroscope, fluorescence spectrophotometer, and
      vibrating sample magnetometer. Experimental observations indicated that the
      composite microparticles had excellent magnetic properties, and its
      photoluminescence could be precisely controlled by varying the number of
      deposition cycles of polyelectrolytes and CdTe/polyelectrolyte multilayers.
      Moreover, the composite microparticles could be heated up in a high-frequency
      magnetic field and demonstrated linear temperature-dependent photoluminescence
      over the range from room temperature to hyperthermia temperature. The composite
      microparticles are expected to be promising candidates for biomedical
      applications, such as immunoassay, biosensing and imaging, and cancer diagnosis
      and treatment.

PMID- 21090659
TI  - Atomic force microscopy force mapping in the study of supported lipid bilayers.
AB  - Investigating the structural and mechanical properties of lipid bilayer membrane
      systems is vital in elucidating their biological function. One route to directly
      correlate the morphology of phase-segregated membranes with their indentation and
      rupture mechanics is the collection of atomic force microscopy (AFM) force maps.
      These force maps, while containing rich mechanical information, require lengthy
      processing time due to the large number of force curves needed to attain a high
      spatial resolution. A force curve analysis toolset was created to perform data
      extraction, calculation and reporting specifically in studying lipid membrane
      morphology and mechanical stability. The procedure was automated to allow for
      high-throughput processing of force maps with greatly reduced processing time.
      The resulting program was successfully used in systematically analyzing a number
      of supported lipid membrane systems in the investigation of their structure and
      nanomechanics.

PMID- 21090660
TI  - Nondestructive three-dimensional analysis of layered polymer structures with
      chemical imaging.
AB  - Three-dimensional (3D) chemical information was obtained by means of a
      combination of two-dimensional attenuated total reflection Fourier transform
      infrared (ATR-FT-IR) imaging with a focal plane array detector and variable angle
      depth profiling. Since the penetration depth of the evanescent wave in ATR
      spectroscopy is not limited by diffraction, it was possible to resolve thin
      sandwiched polymer layers nondestructively within a stack of polymer layers.
      Chemical images were obtained from layers of different thickness of the laminate
      by moving a custom-made aperture to specific positions on the condenser lens of
      the ATR accessory. Sequences of absorption images detect the successive
      appearance of thin, buried layers of polybutylmethacrylate (d(PBMA) = 400 nm) and
      polycarbonate (d(TMPC) = 300 nm) in different depths of the stack of polymer
      layers. The depth resolution of variable-angle ATR-FT-IR imaging is sufficiently
      high to detect surface roughness at the interface between different polymer
      layers. Two different stacks of polymers with reordered sandwich-layers were
      imaged simultaneously, demonstrating the potential of variable angle ATR-FT-IR
      for 3D-imaging of a sample with xyz-heterogeneity, which can be a powerful
      analytical technique for materials science and biomedical research.

PMID- 21090661
TI  - Superhydrophilic and superwetting surfaces: definition and mechanisms of control.
AB  - The term superhydrophobicity was introduced in 1996 to describe water-repellent
      fractal surfaces, made of a hydrophobic material, on which water drops remain as
      almost perfect spheres and roll off such surfaces leaving no residue. Today,
      superhydrophobic surfaces are defined as textured materials (and coatings) on
      (nonsmooth) surfaces on which water forms contact angles 150 degrees  and larger,
      with only a few degrees of contact angle hysteresis (or sliding angle). The terms
      superhydrophilicity and superwetting were introduced a few years after the term
      superhydrophobicity to describe the complete spreading of water or liquid on
      substrates. The definition of superhydrophilic and superwetting substrates has
      not been clarified yet, and unrestricted use of these terms sometimes stirs
      controversy. This Letter briefly reviews the superwetting phenomenon and offers a
      suggestion on defining superhydrophilic and superwetting substrates and surfaces.

PMID- 21090662
TI  - Multivalent interaction of cyclodextrin vesicles, carbohydrate guests, and
      lectins: a kinetic investigation.
AB  - An artificial glycocalix self-assembles when unilamellar bilayer vesicles of
      amphiphilic beta-cyclodextrins are decorated with maltose- and lactose-adamantane
      conjugates by host-guest interactions. The maltose-decorated vesicles aggregate
      in the presence of lectin concanavalin A whereas the lactose-decorated vesicles
      aggregate in the presence of lectin peanut agglutinin. The kinetics of the
      orthogonal multivalent interfacial interactions present in this ternary system of
      vesicles, carbohydrates, and lectins were studied by time-dependent measurements
      of the optical density at 400 nm. The average vesicle and vesicle aggregate sizes
      were monitored by dynamic light scattering. The aggregation process was evaluated
      as a function of lectin concentration, vesicle concentration, and surface
      coverage of the vesicles by the carbohydrate-adamantane conjugates. The initial
      rate of vesicle aggregation scales linearly with the lectin as well as the
      cyclodextrin vesicle concentration. Furthermore, each lectin requires a
      characteristic critical density of carbohydrates at the vesicle surface. These
      observations allow a prediction of the response of the ternary supramolecular
      system at different concentrations of its components. Also, the effective binding
      site separation in a multivalent receptor such as a multiple binding site protein
      can be accurately determined. This methodology can be extended to multivalent
      noncovalent interactions in other ligand-receptor systems at interfaces.

PMID- 21090663
TI  - Nanostructure evolution in high-temperature perfluorosulfonic acid ionomer
      membrane by small-angle X-ray scattering.
AB  - The high-temperature morphology of supported liquid membranes (SLMs) prepared
      from perfluorinated membranes such as Nafion and Hyflon and hydrophobic ionic
      liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMI-TFSI)
      has been investigated by small-angle X-ray scattering (SAXS). Proton conductivity
      results of SLMs before and after leaching show an increase in conductivity with
      temperature up to 160  degrees C in an anhydrous environment. DSC results show
      that crystallites within perfluorinated membranes are thermally stable up to 196 
      degrees C. High-temperature SAXS results have been used to correlate structure
      and morphology of supported liquid membranes with high-temperature conductivity
      data. The ionic liquid essentially acts as a proton solvent in a similar way to
      water in hydrated Nafion membranes and increases size of clusters, which allow
      percolation to be achieved more easily. The cation of the ionic liquid interacts
      with sulfonate groups within ionic domains through electrostatic interactions and
      displaces protons. Protons can associate with free anions of the ionic liquid,
      which are loosely associated with cations and can transport by hopping from anion
      sites within the membrane. The ionic liquid contributes to proton conductivity at
      high temperature through achievement of long-range ordering and subsequent
      percolation.

PMID- 21090665
TI  - Ultra-long-range electron transfer through a self-assembled monolayer on gold
      composed of 120-A-long alpha-helices.
AB  - Electron transfer through alpha-helices has attracted much attention from the
      viewpoints of their contributions to efficient long-range electron transfer
      occurring in biological systems and their utility as molecular-electronics
      elements. In this study, we synthesized a long 80mer helical peptide carrying a
      redox-active ferrocene unit at the terminal and immobilized the helical peptide
      on a gold surface. The molecular length is calculated to be 134 A, in which the
      helix accounts for 120 A. The preparation conditions of the self-assembled
      monolayers were intentionally changed to obtain monolayers with different
      physical states to study the correlation between molecular motions and electron
      transfer. Ellipsometry and infrared spectroscopy showed that the helical peptide
      forms a self-assembled monolayer with vertical orientation. Electrochemical
      measurements revealed that an electron is transferred from the ferrocene unit to
      gold through the monolayer composed of this long helical peptide, and the
      experimental data are well explained by theoretical results calculated under the
      assumption that electron transfer occurs by a unique hopping mechanism with the
      amide groups as hopping sites. Furthermore, we have observed a unique dependence
      of electron transfer on the monolayer packing, suggesting the importance of
      structural fluctuations of peptides on the electron transfer controlled by the
      hopping mechanism.

PMID- 21090664
TI  - Functionalization of sol gel bioactive glasses carrying Au nanoparticles:
      selective Au affinity for amino and thiol ligand groups.
AB  - It is demonstrated here that bioactive glasses containing Au nanoparticles
      (AuNPs) can be selectively functionalized with small molecules carrying either
      amino or thiol groups by simply varying the temperature and pH of the
      functionalization batch. The results evidence the following. (i) At room
      temperature (RT), no functionalization of Au-free glass occurs, whereas in the
      case of glasses containing AuNPs, stable linkages form only with amino groups, as
      in this condition Au does not bind with either thiol or hydroxyl groups. The RT
      functionalization with cysteine and cystine confirms the preferential
      functionalization through the amino groups, while the -SH groups are oxidized to
      S-S bridges. (ii) The functionalization with cysteine and cystine, compared at pH
      = 5, 9, and 12, is shown not to take place at pH = 5 and to be hindered by the
      glass matrix dissolution at pH = 12 (with consequent release of AuNPs), while the
      best results are obtained at pH = 9. (iii) For the effect of reaction
      temperature, at 4  degrees C it is possible to obtain a strong Au-S interaction,
      whereas at RT, a weak Au-N linkage is formed. These results should allow
      production, in a selective way, of different bonds exhibiting different strengths
      and, consequently, different release times in solution, with a wide range of
      possible applications (for instance, weak Au-N bonds in the case of drug
      delivery, strong Au-S bonds in protein immobilization).

PMID- 21090666
TI  - Metabonomic study of Chinese medicine Shuanglong formula as an effective
      treatment for myocardial infarction in rats.
AB  - A UPLC/TOF-MS-based metabonomic study was conducted to assess the holistic
      efficacy of Traditional Chinese Medicine Shuanglong Formula (SLF) for myocardial
      infarction in rats. Thirty male Sprague-Dawley rats were randomly divided into
      five groups after surgery. The Panax ginseng group, Salvia miltiorrhiza group,
      and SLF group were treated with water extractions of Panax ginseng (PG), Salvia
      miltiorrhiza (SM), and SLF (the ratio of SM to PG was 3:7) at a dose of 5
      g/kg.w.d for 21 consecutive days, respectively; the model group and sham surgery
      group were both treated with 0.9% saline solution. Urinary samples for
      metabonomic study, serum samples for biochemical measurement, and heart samples
      for histopathology were collected. As a result, metabonomics-based findings such
      as the PCA and PLS-DA plotting of metabolic state and analysis of potential
      biomarkers in urine correlated well to the assessment of serum biochemistry and
      histopathological assay, confirming that SLF exerted synergistic therapeutic
      efficacies to exhibit better effect on MI compared to PG or SM. The shifts in
      urinary TCA cycle as well as pentose phosphate pathway suggested that SLF may
      diminish cardiac injury of MI with its potential pharmacological effect in the
      regulation of myocardial energy metabolism.

PMID- 21090668
TI  - Measuring porosity at the nanoscale by quantitative electron tomography.
AB  - Quantitative electron tomography is proposed to characterize porous materials at
      a nanoscale. To achieve reliable three-dimensional (3D) quantitative information,
      the influence of missing wedge artifacts and segmentation methods is
      investigated. We are presenting the "Discrete Algebraic Reconstruction Algorithm"
      as the most adequate tomography method to measure porosity at the nanoscale. It
      provides accurate 3D quantitative information, regardless the presence of a
      missing wedge. As an example, we applied our approach to nanovoids in La2Zr2O7
      thin films.

PMID- 21090669
TI  - Infrared spectra of protonated neurotransmitters: serotonin.
AB  - The gas-phase IR spectrum of the protonated neurotransmitter serotonin (5
      hydroxytryptamine) was measured in the fingerprint range by means of IR multiple
      photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum was recorded in a
      Fourier transform ion cyclotron resonance mass spectrometer coupled to an
      electrospray ionization source and an IR free electron laser. Quantum chemical
      calculations at the B3LYP and MP2 levels of theory using the cc-pVDZ basis set
      yield six low-energy isomers in the energy range up to 40 kJ/mol, all of which
      are protonated at the amino group. Protonation at the indole N atom or the
      hydroxyl group is substantially less favorable. The IRMPD spectrum is rich in
      structure and exhibits 22 distinguishable features in the spectral range
      investigated (530-1885 cm(-1)). The best agreement between the measured IRMPD
      spectrum and the calculated linear IR absorption spectra is observed for the
      conformer lowest in energy at both levels of theory, denoted g-1. In this
      structure, one of the three protons of the ammonium group points toward the
      indole subunit, thereby maximizing the intramolecular NH(+)-pi interaction
      between the positive charge of the ammonium ion and the aromatic indole ring.
      This mainly electrostatic cation-pi interaction is further stabilized by
      significant dispersion forces, as suggested by the substantial differences
      between the DFT and MP2 energies. The IRMPD bands are assigned to individual
      normal modes of the g-1 conformer, with frequency deviations of less than 29 cm(
      1) (average <13 cm(-1)). The effects of protonation on the geometric and
      electronic structure are revealed by comparison with the corresponding
      structural, energetic, electronic, and spectroscopic properties of neutral
      serotonin.

PMID- 21090670
TI  - The role of high work-function metallic nanodots on the performance of a-Si:H
      solar cells: offering ohmic contact to light trapping.
AB  - Addition of carbon into p-type "window" layers in hydrogenated amorphous silicon
      (a-Si:H) solar cells enhances short circuit currents and open circuit voltages by
      a great deal. However, a-Si:H solar cells with high carbon-doped "window" layers
      exhibit poor fill factors due to a Schottky barrier-like impedance at the
      interface between a-SiC:H windows and transparent conducting oxides (TCO),
      although they show maximized short circuit currents and open circuit voltages.
      The impedance is caused by an increasing mismatch between the work function of
      TCO and that of p-type a-SiC:H. Applying ultrathin high-work-function metals at
      the interface between the two materials results in an effective lowering of the
      work function mismatch and a consequent ohmic behavior. If the metal layer is
      sufficiently thin, then it forms nanodots rather than a continuous layer which
      provides light-scattering effect. We demonstrate 31% efficiency enhancement by
      using high-work-function materials for engineering the work function at the key
      interfaces to raise fill factors as well as photocurrents. The use of metallic
      interface layers in this work is a clear contrast to previous work where attempts
      were made to enhance the photocurrent using plasmonic metal nanodots on the solar
      cell surface.

PMID- 21090671
TI  - Single molecule atomic force microscopy studies of photosensitized singlet oxygen
      behavior on a DNA origami template.
AB  - DNA origami, the folding of a long single-stranded DNA sequence (scaffold strand)
      by hundreds of short synthetic oligonucleotides (staple strands) into parallel
      aligned helices, is a highly efficient method to form advanced self-assembled DNA
      architectures. Since molecules and various materials can be conjugated to each of
      the short staple strands, the origami method offers a unique possibility of
      arranging molecules and materials in well-defined positions on a structured
      surface. Here we combine the action of light with AFM and DNA nanostructures to
      study the production of singlet oxygen from a single photosensitizer molecule
      conjugated to a selected DNA origami staple strand on an origami structure. We
      demonstrate a distance-dependent oxidation of organic moieties incorporated in
      specific positions on DNA origami by singlet oxygen produced from a single
      photosensitizer located at the center of each origami.

PMID- 21090672
TI  - Ga(OTf)3-catalyzed direct substitution of alcohols with sulfur nucleophiles.
AB  - It is reported that Ga(OTf)(3) catalyzes the direct displacement of alcohols with
      sulfur nucleophiles. The products are versatile intermediates that can be
      utilized in carbon-carbon, carbon-sulfur bond formation or used in modified Julia
      olefination reactions. The only byproduct generated is water.

PMID- 21090673
TI  - Ultralight multiwalled carbon nanotube aerogel.
AB  - Ultralight multiwalled carbon nanotube (MWCNT) aerogel is fabricated from a wet
      gel of well-dispersed pristine MWCNTs. On the basis of a theoretical prediction
      that increasing interaction potential between CNTs lowers their critical
      concentration to form an infinite percolation network, poly(3-(trimethoxysilyl)
      propyl methacrylate) (PTMSPMA) is used to disperse and functionalize MWCNTs where
      the subsequent hydrolysis and condensation of PTMSPMA introduces strong and
      permanent chemical bonding between MWCNTs. The interaction is both experimentally
      and theoretically proven to facilitate the formation of a MWCNT percolation
      network, which leads to the gelation of MWCNT dispersion at ultralow MWCNT
      concentration. After removing the liquid component from the MWCNT wet gel, the
      lightest ever free-standing MWCNT aerogel monolith with a density of 4 mg/cm(3)
      is obtained. The MWCNT aerogel has an ordered macroporous honeycomb structure
      with straight and parallel voids in 50-150 MUm separated by less than 100 nm
      thick walls. The entangled MWCNTs generate mesoporous structures on the honeycomb
      walls, creating aerogels with a surface area of 580 m(2)/g which is much higher
      than that of pristine MWCNTs (241 m(2)/g). Despite the ultralow density, the
      MWCNT aerogels have an excellent compression recoverable property as demonstrated
      by the compression test. The aerogels have an electrical conductivity of 3.2 *
      10(-2) S.cm(-1) that can be further increased to 0.67 S.cm(-1) by a high-current
      pulse method without degrading their structures. The excellent compression
      recoverable property, hierarchically porous structure with large surface area,
      and high conductivity grant the MWCNT aerogels exceptional pressure and chemical
      vapor sensing capabilities.

PMID- 21090674
TI  - Fabrication of the funnel-shaped three-dimensional plasmonic tip arrays by
      directional photofluidization lithography.
AB  - Plasmonics allow localization of an electromagnetic (EM) field into nanoscale
      "hotspots", a feature that is of technological significance due to potential
      applications related to spectroscopic sensing and nanofocusing. In relation to
      this, many researchers have sought to fabricate metallic nanostructures with
      sharp edges, as they provide much higher EM field enhancement compared with
      rounded structures. However, a fabrication method satisfying stringent
      requirements for the efficient EM field enhancement including three
      dimensionality, vertical orientation, large-area fabrication, and tunability of
      structural features, which are of practical importance for efficient plasmonic
      light enhancement at hotspots, has yet to be achieved. Herein, we fabricate large
      area, vertically aligned three-dimensional plasmonic tip (i.e., nanofunnel)
      arrays with unprecedented flexibility in the control of the structural features
      by directional photofluidization lithography. Using this approach, the structural
      features of nanofunnel tips including the sharpness, shape, and orientation were
      precisely controlled in a scalable and deterministic manner. The effects of the
      structural features of the nanofunnel on the EM field enhancement were
      systematically investigated and analyzed, and the optimum tip features for
      maximum EM field enhancement were thereupon identified. The suggested
      nanofabrication technique and resulting structures will be of practical
      importance in spectroscopic and nanophotonic applications.

PMID- 21090675
TI  - Intermolecular reductive radical addition to 2-(2,2,2-trifluoroethylidene)-1,3
      dithiane 1-oxide: experimental and theoretical studies.
AB  - Tin hydride mediated radical addition of organic halide to 2-(2,2,2
      trifluoroethylidene)-1,3-dithiane 1-oxide has been devised. The reaction is
      equivalent to an unrealizable radical addition to trifluoromethylketene,
      providing useful alpha-trifluoromethyl carbonyl equivalents. The trifluoromethyl
      and the sulfoxide groups of the substrate play key roles for the success of the
      radical addition, lowering the barrier of the radical addition step and
      controlling the stereoselectivity of the reaction, which DFT calculations have
      elucidated.

PMID- 21090676
TI  - Preparation of p-type CaFe2O4 photocathodes for producing hydrogen from water.
AB  - An (hk0)-oriented p-type CaFe2O4 (E(g): 1.9 eV) photocathode was prepared, and
      hydrogen and oxygen gases were produced from a photocell short-circuited by
      connecting the CaFe2O4 and n-type TiO2 electrodes under illumination without
      applying an external voltage. The open-circuited voltage was 0.97 V and the short
      circuit current was about 200 MUA/cm(2), and the amount of evaluated hydrogen and
      oxygen gases after 2 days of reaction were about 70 and 4 MUmol, respectively.

PMID- 21090677
TI  - Oxygen plasma etching-induced crystalline lattice transformation of colloidal
      photonic crystals.
AB  - This communication describes the transformation of a colloidal crystalline
      lattice that was realized via oxygen plasma etching of colloidal crystals made of
      SiO2@PMMA core-shell microspheres. The plasma etching of the colloidal crystals
      proceeded nonuniformly from the top to the bottom of the colloidal crystals. The
      PMMA shell was etched away by the oxygen plasma in a layer-by-layer manner, and
      the silica core was drawn into the pit formed by the neighboring spheres in the
      layer below. Consequently, the crystalline lattice was transformed while the
      order was maintained. Scanning electron microscopy images and reflection spectra
      further confirmed the change in the crystalline structures. Colloidal crystals
      with sc and bcc lattices can be fabricated if the ratio of the polymer shell
      thickness to the silica core diameter is equal to certain values. More
      importantly, this approach may be applicable to the fabrication of various
      assembly structures with different inorganic particles.

PMID- 21090678
TI  - Tripodal tris-tacn and tris-dpa platforms for assembling phosphate-templated
      trimetallic centers.
AB  - Multidentate tripodal ligands, N(CH2-m-C6H4-CH2tacn)3 (L1) and N(CH2-o-C6H4
      CH2N(CH2py)2)3 (L2), have been devised for assembling high-nuclearity metal
      clusters. By using the same tripodal platform with different ligand appendages,
      either triazacyclononanes or dipicolylamines, and functionalizing either the
      ortho or the meta positions on the tris(xylyl) linker arms, discrete trimetal
      phosphate units of relevance to phosphate-metabolizing trimetallic centers in
      biology were prepared. Four such compounds, [(Cu(II)Cl)3(HPO4)L1](PF6) (1),
      [(Cu(II)Cl)3(HAsO4)L1](PF6) (2), Na2[Mn(III)6Mn(II)2(H2O)2(HPO4)6(PO4)4(L1)2]
      (3), and [Co(II)3(H2PO4)Cl2(MeCN)L2](PF6)3 (4), all containing three metal
      centers bound to a central phosphate or arsenate unit bridging oxygen atoms, have
      been synthesized and structurally characterized. These results demonstrate the
      propensity of this novel tripodal ligand platform, in the presence of phosphate
      or arsenate, to assemble {M3(EO4)} units and thus structurally mimic trimetallic
      active sites of proteins involved in phosphate metabolism. Reactivity studies
      reveal that the tricopper complex 1 is more efficient than monocopper analogues
      in catalyzing the hydrolysis of 4-nitrophenyl phosphate.

PMID- 21090679
TI  - Determination of alcohol and extract concentration in beer samples using a
      combined method of near-infrared (NIR) spectroscopy and refractometry.
AB  - A new approach of combination of near-infrared (NIR) spectroscopy and
      refractometry was developed in this work to determine the concentration of
      alcohol and real extract in various beer samples. A partial least-squares (PLS)
      regression, as multivariate calibration method, was used to evaluate the
      correlation between the data of spectroscopy/refractometry and alcohol/extract
      concentration. This multivariate combination of spectroscopy and refractometry
      enhanced the precision in the determination of alcohol, compared to single
      spectroscopy measurements, due to the effect of high extract concentration on the
      spectral data, especially of nonalcoholic beer samples. For NIR calibration, two
      mathematical pretreatments (first-order derivation and linear baseline
      correction) were applied to eliminate light scattering effects. A sample grouping
      of the refractometry data was also applied to increase the accuracy of the
      determined concentration. The root mean squared errors of validation (RMSEV) of
      the validation process concerning alcohol and extract concentration were 0.23
      Mas% (method A), 0.12 Mas% (method B), and 0.19 Mas% (method C) and 0.11 Mas%
      (method A), 0.11 Mas% (method B), and 0.11 Mas% (method C), respectively.

PMID- 21090680
TI  - Changes in the contents of sugars and organic acids during the ripening and
      storage of sufu, a traditional Oriental fermented product of soybean cubes.
AB  - In the present study, sufu, an oriental fermented product of soybeans, was
      prepared by ripening the tofu cubes in Aspergillus oryzae fermented rice-soybean
      koji mash for 16 days at 37  degrees C. The sufu product was further kept at room
      temperature for another 30 days. Examining the changes in the sugar content
      revealed that stachyose, raffinose, and sucrose contents of tofu and rice-soybean
      koji granules decreased while levels of glucose and fructose increased during the
      ripening period and after storage. Glucose was the most abundant sugar detected.
      Four organic acids, including oxalic, lactic, acetic, and citric acid, were
      detected in the sufu product and koji granules after ripening. Generally, the
      contents of these organic acid increased as the ripening period was extended.
      Among them, acetic acid was the most highly detected.

PMID- 21090681
TI  - Diadenosine 5',5''-(boranated)polyphosphonate analogues as selective nucleotide
      pyrophosphatase/phosphodiesterase inhibitors.
AB  - Nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyze extracellular
      nucleotides and dinucleotides and thus control purinergic signaling. Enhanced NPP
      activity is implicated in health disorders such as osteoarthritis and cancer. We
      designed novel diadenosine polyphosphonate derivatives as potential NPP
      inhibitors. Analogues 1-4 bear a phosphonate and/or boranophosphate group and/or
      a 2'-H atom instead of a 2'-OH group. In comparison to ATP, analogues 1-4 were
      barely hydrolyzed by human NTPDase1, -2, -3, and -8 (<5% hydrolysis) and NPP1 and
      -3 (<= 13%) and were not hydrolyzed by ecto-5'-nucleotidase, unlike AMP. These
      derivatives did not affect NTPDase activity, and analogues 1 and 2 did not
      inhibit ecto-5'-nucleotidase. All analogues blocked ~80% of the NPP2-dependent
      hydrolysis of pnp-TMP, a specific NPP substrate, and inhibited the catabolism of
      pnp-TMP (K(i) and IC50 both found to be between 10 and 60 MUM), Ap5A, and ATP by
      NPP1. The activity of NPP3 was inhibited to a lesser extent by the new analogues,
      with compounds 1 and 4 being the most effective in that respect. The analogues
      dramatically reduced the level of hydrolysis of pnp-TMP at the cell surface of
      both osteocarcinoma and colon cancer cells. Importantly, analogues 1-4 exhibited
      significantly reduced agonistic activity toward human P2Y1,11) receptors (except
      for analogue 1) and no activity with human P2Y2 receptor. Our data provide strong
      evidence that analogue 2 is the first specific NPP inhibitor to be described.

PMID- 21090682
TI  - Structure-based design, synthesis, and pharmacological evaluation of 3
      (aminoalkyl)-5-fluoroindoles as myeloperoxidase inhibitors.
AB  - Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and
      promote local inflammation, which contributes to the progression of the
      atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is
      related to its ability to modify APO B-100 in the intima and at the surface of
      endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was
      designed and synthesized by exploiting the structure-based docking of 5
      fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the
      effects of these compounds on the inhibition of MPO-mediated taurine chlorination
      and oxidation of LDLs. The kinetics of the interaction between the MPO redox
      intermediates, Compounds I and II, and these inhibitors was also investigated.
      The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no
      substituent on the amino group. The mode of binding of these analogues and the
      mechanism of inhibition is discussed with respect to the structure of MPO and its
      halogenation and peroxidase cycles.

PMID- 21090683
TI  - Soft microelectrode linear array for scanning electrochemical microscopy.
AB  - A linear array of eight individual addressable microelectrodes has been developed
      in order to perform high-throughput scanning electrochemical microscopy (SECM)
      imaging of large sample areas in contact regime. Similar to previous reports, the
      soft microelectrode array was fabricated by ablating microchannels on a
      polyethylene terephthalate (PET) film and filling them with carbon ink.
      Improvements have been achieved by using a 5 MUm thick Parylene coating that
      allows for smaller working distances, as the probe was mounted with the Parylene
      coating facing the sample surface. Additionally, the application of a SECM holder
      allows scanning in contact regime with a tilted probe, reducing the topographic
      effects and assuring the probe bending direction. The main advantage of the soft
      microelectrode array is the considerable decrease in the experimental time needed
      for imaging large sample areas. Additionally, soft microelectrode arrays are very
      stable and can be used several times, since the electrode surface can be
      regenerated by blade cutting. Cyclic voltammograms and approach curves were
      recorded in order to assess the electrochemical properties of the device. An SECM
      image of a gold on glass chip was obtained with high resolution and sensitivity,
      proving the feasibility of soft microelectrode arrays to detect localized surface
      activity. Finite element method (FEM) simulations were performed in order to
      establish the effect of diffusion layer overlapping between neighboring
      electrodes on the respective approach curves.

PMID- 21090684
TI  - Comparative study of virgin olive oil quality from single varieties cultivated in
      Chile and Spain.
AB  - Olive tree varieties that were cultivated only in the Mediterranean basin a few
      decades ago are now planted in the Southern Hemisphere as well. The chemical
      composition of the oils produced in countries as far distant as Spain and Chile
      are affected by differences in latitude and climate. In this work, seven
      monovarietal virgin olive oils from Chile (Arbequina, Barnea, Frantoio,
      Koroneiki, Leccino, Manzanilla and Picual) have been characterized by the
      chemical compounds responsible for taste (phenols) and aroma (volatiles). The
      oils were produced in five regions of Chile, and the concentration values of some
      chemical compounds were related to the geographical location of the olive tree
      orchards. Virgin olive oils from the major cultivars, Arbequina and Picual, were
      characterized in comparison with the same monovarietal oils produced in Spain.
      The concentration values of fourteen volatile compounds showed significant
      differences (p < 0.05) between the oils produced in Spain and Chile. Concerning
      the phenol composition, main differences were found on the secoiridoids
      derivatives of oleuropein and ligstroside, apigenin and luteolin.

PMID- 21090685
TI  - Dioxythiophene-based polymer electrodes for supercapacitor modules.
AB  - We report on the electrochemical and capacitive behaviors of poly(2,2-dimethyl
      3,4-propylene-dioxythipohene) (PProDOT-Me2) films as polymeric electrodes in Type
      I electrochemical supercapacitors. The supercapacitor device displays robust
      capacitive charging/discharging behaviors with specific capacitance of 55 F/g,
      based on 60 MUg of PProDOT-Me2 per electrode, that retains over 85% of its
      storage capacity after 32 000 redox cycles at 78% depth of discharge. Moreover,
      an appreciable average energy density of 6 Wh/kg has been calculated for the
      device, along with well-behaved and rapid capacitive responses to 1.0 V between 5
      to 500 mV s(-1). Tandem electrochemical supercapacitors were assembled in series,
      in parallel, and in combinations of the two to widen the operating voltage window
      and to increase the capacitive currents. Four supercapacitors coupled in series
      exhibited a 4.0 V charging/discharging window, whereas assembly in parallel
      displayed a 4-fold increase in capacitance. Combinations of both serial and
      parallel assembly with six supercapacitors resulted in the extension of voltage
      to 3 V and a 2-fold increase in capacitive currents. Utilization of bipolar
      electrodes facilitated the encapsulation of tandem supercapacitors as individual,
      flexible, and lightweight supercapacitor modules.

PMID- 21090686
TI  - Identification and characterization of a luciferase isotype in the Japanese
      firefly, Luciola cruciata, involving in the dim glow of firefly eggs.
AB  - We isolated the cDNA of a luciferase isotype (LcLuc2) from the Japanese firefly,
      Luciola cruciata (Lampyridae, Coleoptera). The gene product of LcLuc2 (LcLuc2)
      showed 59% amino acid identity with firefly luciferase LcLuc1, which was
      previously identified in L. cruciata. The recombinant LcLuc2 showed both
      luminescence activity and fatty acyl-CoA synthetic activity comparable to those
      of LcLuc1. The spectral maxima of the luminescence by LcLuc1 and LcLuc2 were 554
      and 543 nm, respectively. Reverse transcription-PCR analysis showed that the
      transcripts of LcLuc1 were abundant in the lanterns of larva, adult male, and
      adult female, whereas both LcLuc1 and LcLuc2 were expressed in eggs. The
      luminescence spectra of the lantern extracts from larva, adult male, and adult
      female were in good agreement with that of recombinant LcLuc1. On the other hand,
      the emission maximum of the extract from eggs was between those of LcLuc1 and
      LcLuc2. These results suggest that L. cruciata possesses two luciferases: LcLuc1
      is responsible for the major luminescence in larva and adult, whereas LcLuc1 and
      LcLuc2 are responsible for the dim glow in firefly eggs.

PMID- 21090687
TI  - Near-infrared luminescence from visible-light-sensitized hybrid materials
      covalently linked with tris(8-hydroxyquinolinate)-lanthanide [Er(III), Nd(III),
      and Yb(III)] derivatives.
AB  - A series of new near-infrared (NIR) luminescent lanthanide-quinolinate
      derivatives [Ln(Q-Si)(3)] and xerogels (named as LnQSi-Gel, Ln = Er, Nd, Yb)
      covalently linked with the Ln(Q-Si)(3) by using the 8-hydroxyquinoline
      functionalized alkoxysilane (Q-Si) have been synthesized. The obtained xerogel
      materials LnQSi-Gel are rigid and show homogeneous by field-emission scanning
      electron microscopy (FE-SEM) images. The Fourier-transform infrared (FT-IR),
      fluorescence spectra of Ln(Q-Si)(3), and LnQSi-Gel were measured, and the
      corresponding luminescence decay analyses were recorded. Of importance here is
      that the excitation spectra of the Ln(Q-Si)(3) and LnQSi-Gel extend to the region
      of visible light (more than 500 nm). Upon ligand-mediated excitation with the
      visible light, the Ln(Q-Si)(3) and LnQSi-Gel show the characteristic NIR
      luminescence of the corresponding lanthanide ions through the intramolecular
      energy transfer from the ligands to the lanthanide ions. The good luminescent
      performances enable these NIR-luminescent xerogel materials to have possible
      applications in medical diagnostics, laser systems, and optics, etc.

PMID- 21090689
TI  - Facile synthesis and characterization of phosphorescent Pt(N(?)C(?)N)X complexes.
AB  - In order to investigate the ground state and excited state properties of
      Pt(N(?)C(?)N)X, we have prepared a series of Pt complexes, where N(?)C(?)N
      aromatic chelates are derivatives of m-di(2-pyridinyl)benzene (dpb) and X are
      monoanionic and monodentate ancillary ligands including halide and phenoxide.
      Facile synthesis of platinum m-di(2-pyridinyl)benzene chloride and its
      derivatives, using controlled microwave heating, was reported. This method not
      only shortened the reaction time but also improved the reaction yield for most of
      the Pt complexes. Two Pt(N(?)C(?)N)X complexes have been structurally
      characterized by X-ray crystallography. The change of functional group does not
      affect the structure of the core Pt(N(?)C(?)N)Cl fragment. Both molecules pack as
      head-to-tail dimers, each molecule of the dimer related to the other by a center
      of inversion. The electrochemical studies of all Pt complexes demonstrate that
      the oxidation process occurs on the metal-phenyl fragment and the reduction
      process is associated with the electron accepting groups like pyridinyl groups
      and their derivatives. The maximum emission wavelength of the Pt(N(?)C(?)N)X
      complexes ranges between 471 and 610 nm, crossing the spectrum of visible light.
      Most of the Pt complexes are strongly luminescent (Phi = 0.32-0.63) and have
      short luminescence lifetimes (tau = 4-7 MUs) at room temperature. The lowest
      excited state of the Pt(N(?)C(?)N)X complexes is identified as a dominant ligand
      centered (3)pi-pi* state with some (1)MLCT/(3)MLCT character, which appears to
      have a larger (1)MLCT component than their bidentate and tridentate analogs. This
      results in a high radiative decay rate and high quantum yield for Pt(dpb)Cl and
      its analogs. However, the excited state properties of the Pt(N(?)C(?)N)X
      complexes are strongly dependent on the nature of the electron-accepting groups
      and substituents to the metal-phenyl fragment. A rational design will be needed
      to tune the emission energies of the Pt(N(?)C(?)N)X complexes over a wide range
      while maintaining their high luminescent efficiency.

PMID- 21090688
TI  - Electrochemical characterization of thin film electrodes toward developing a DNA
      transistor.
AB  - The DNA-Transistor is a device designed to control the translocation of single
      stranded DNA through a solid-state nanopore. Functionality of the device is
      enabled by three electrodes exposed to the DNA-containing electrolyte solution
      within the pore and the application of a dynamic electrostatic potential well
      between the electrodes to temporarily trap a DNA molecule. Optimizing the surface
      chemistry and electrochemical behavior of the device is a necessary (but by no
      means sufficient) step toward the development of a functional device. In
      particular, effects to be eliminated are (i) electrochemically induced surface
      alteration through corrosion or reduction of the electrode surface and (ii)
      formation of hydrogen or oxygen bubbles inside the pore through water
      decomposition. Even though our motivation is to solve problems encountered in DNA
      transistor technology, in this paper we report on generic surface chemistry
      results. We investigated a variety of electrode-electrolyte-solvent systems with
      respect to their capability of suppressing water decomposition and maintaining
      surface integrity. We employed cyclic voltammetry and long-term amperometry as
      electrochemical test schemes, X-ray photoelectron spectroscopy, atomic force
      microscopy, and scanning, as well as transmission electron microscopy as
      analytical tools. Characterized electrode materials include thin films of Ru, Pt,
      nonstoichiometric TiN, and nonstoichiometric TiN carrying a custom-developed
      titanium oxide layer, as well as custom-oxidized nonstoichiometric TiN coated
      with a monolayer of hexadecylphosphonic acid (HDPA). We used distilled water as
      well as aqueous solutions of poly(ethylene glycol) (PEG-300) and glycerol as
      solvents. One millimolar KCl was employed as electrolyte in all solutions. Our
      results show that the HDPA-coated custom-developed titanium oxide layer
      effectively passivates the underlying TiN layer, eliminating any surface
      alterations through corrosion or reduction within a voltage window from -2 V to
      +2 V. Furthermore, we demonstrated that, by coating the custom-oxidized TiN
      samples with HDPA and increasing the concentration of PEG-300 or glycerol in
      aqueous 1 mM KCl solutions, water decomposition was suppressed within the same
      voltage window. Water dissociation was not detected when combining custom
      oxidized HDPA-coated TiN electrodes with an aqueous 1 mM KCl-glycerol solution at
      a glycerol concentration of at least 90%. These results are applicable to any
      system that requires nanoelectrodes placed in aqueous solution at voltages that
      can activate electrochemical processes.

PMID- 21090690
TI  - Dynamics of light-induced activation in the PAS domain proteins LOV2 and PYP
      probed by time-resolved tryptophan fluorescence.
AB  - Light-induced activation of the LOV2-Jalpha domain of the photoreceptor
      phototropin from oat is believed to involve the detachment of the Jalpha helix
      from the central beta-sheet and its subsequent unfolding. The dynamics of these
      conformational changes were monitored by time-resolved emission spectroscopy with
      100 ns time resolution. Three transitions were detected during the LOV2-Jalpha
      photocycle with time constants of 3.4 MUs, 500 MUs, and 4.3 ms. The fastest
      transition is due to the decay of the flavin phosphorescence in the transition of
      the triplet LOV(L)(660) state to the singlet LOV(S)(390) signaling state. The 500
      MUs and 4.3 ms transitions are due to changes in tryptophan fluorescence and may
      be associated with the dissociation and unfolding of the Jalpha helix,
      respectively. They are absent in the transient absorption signal of the flavin
      chromophore. The tryptophan fluorescence signal monitors structural changes
      outside the chromophore binding pocket and indicates that there are at least
      three LOV(S)(390) intermediates. Since the 500 MUs and 4.3 ms components are
      absent in a construct without the Jalpha helix and in the mutant W557S, the
      fluorescence signal is mainly due to tryptophan 557. The kinetics of the main 500
      MUs component is strongly temperature dependent with activation energy of 18.2
      kcal/mol suggesting its association with a major structural change. In the
      structurally related PAS domain protein PYP the N-terminal cap dissociates from
      the central beta-sheet and unfolds upon signaling state formation with a similar
      time constant of ~1 ms. Using transient fluorescence we obtained a nearly
      identical activation energy of 18.5 kcal/mol for this transition.

PMID- 21090691
TI  - Calcium-promoted Pictet-Spengler reactions of ketones and aldehydes.
AB  - Calcium bis-1,1,1,3,3,3-hexafluoroisopropoxide is shown to be an effective
      catalyst for Pictet-Spengler reactions of 3-hydroxyphenethylamine and 3-hydroxy-4
      methoxyphenethylamine with various aldehydes and ketones. Previous Lewis acid
      catalyzed Pictet-Spengler reactions of unactivated ketones typically require two
      separate reactions (imine formation, cyclization) to obtain the same results. The
      reactions described within directly provide 1,1'-disubstituted
      tetrahydroisoquinolines from the corresponding amine and ketone. These rare
      examples of Pictet-Spengler reactions of unactivated ketones demonstrate the
      unique nature of calcium as a Lewis acid catalyst.

PMID- 21090692
TI  - Germylenes: structures, electron affinities, and singlet-triplet gaps of the
      conventional XGeCY(3) (X = H, F, Cl, Br, and I; Y = F and Cl) species and the
      unexpected cyclic XGeCY(3) (Y = Br and I) systems.
AB  - A systematic investigation of the X-Ge-CY(3) (X = H, F, Cl, Br, and I; Y = F, Cl,
      Br, and I) species is carried out using density functional theory. The basis sets
      used for all atoms (except iodine) in this work are of double-zeta plus
      polarization quality with additional s- and p-type diffuse functions, and denoted
      DZP++. Vibrational frequency analyses are performed to evaluate zero-point energy
      corrections and to determine the nature of the stationary points located.
      Predicted are four different forms of neutral-anion separations: adiabatic
      electron affinity (EA(ad)), zero-point vibrational energy corrected EA(ad(ZPVE)),
      vertical electron affinity (EA(vert)), and vertical detachment energy (VDE). The
      electronegativity (chi) reactivity descriptor for the halogens (X = F, Cl, Br,
      and I) is used as a tool to assess the interrelated properties of these
      germylenes. The topological position of the halogen atom bound to the divalent
      germanium center is well correlated with the trend in the electron affinities and
      singlet-triplet gaps. For the expected XGeCY(3) structures (X = H, F, Cl, Br, and
      I; Y = F and Cl), the predicted trend in the electron affinities is well
      correlated with simpler germylene derivatives (J. Phys. Chem. A 2009, 113, 8080).
      The predicted EA(ad(ZPVE)) values with the BHLYP functional range from 1.66 eV
      (FGeCCl(3)) to 2.20 eV (IGeCF(3)), while the singlet-triplet splittings range
      from 1.28 eV (HGeCF(3)) to 2.22 eV (FGeCCl(3)). The XGeCY(3) (Y = Br and I)
      species are most often characterized by three-membered cyclic systems involving
      the divalent germanium atom, the carbon atom, and a halogen atom.

PMID- 21090693
TI  - Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo.
AB  - Nanoparticle-based therapeutics with local delivery and external electromagnetic
      field modulation holds extraordinary promise for soft-tissue cancers such as
      breast cancer; however, knowledge of the distribution and fate of nanoparticles
      in vivo is crucial for clinical translation. Here we demonstrate that multiple
      diagnostic capabilities can be introduced in photothermal therapeutic
      nanocomplexes by simultaneously enhancing both near-infrared fluorescence and
      magnetic resonance imaging (MRI). We track nanocomplexes in vivo, examining the
      influence of HER2 antibody targeting on nanocomplex distribution over 72 h. This
      approach provides valuable, detailed information regarding the distribution and
      fate of complex nanoparticles designed for specific diagnostic and therapeutic
      functions.

PMID- 21090694
TI  - Induced production of bromomethylchlamydosporols A and B from the marine-derived
      fungus Fusarium tricinctum.
AB  - The addition of CaBr(2) to the fermentation of a marine-derived Fusarium
      tricinctum resulted in production of halogenated chlamydosporol analogues. Two
      new antimicrobial halogenated pyranopyranones, bromomethylchlamydosporols A (1)
      and B (2), and two known compounds, chlamydosporol (an inseparable epimeric
      mixture of 7R:7S = 1:1 from (1)H NMR data) (3) and fusarielin A (4), were
      isolated from the culture. The structures of 1 and 2 were assigned through a
      combination of spectroscopic data analyses. Compounds 1-4 exhibited mild
      antibacterial activity against Staphylococcus aureus, methicillin-resistant S.
      aureus, and multidrug-resistant S. aureus. The MIC values of each strain were as
      follows: compounds 1 and 2 showed an MIC of 15.6 MUg/mL against S. aureus,
      methicillin-resistant S. aureus, and multidrug-resistant S. aureus, and compounds
      3 and 4 exhibited an MIC of 31.5 MUg/mL against S. aureus and methicillin
      resistant S. aureus and 62.5 MUg/mL against multidrug-resistant S. aureus.

PMID- 21090695
TI  - Luminescent, redox-active diphenothiazine dumbbells expanded by conjugated arenes
      and heteroarenes.
AB  - Dumbbell-shaped diphenothiazines bridged by conjugatively linked (hetero)aromatic
      moieties were synthesized in a modular fashion by Suzuki-Miyaura coupling in good
      yields. The electronic structure was studied by DFT computations, determining the
      geometry optimized lowest energy conformers and scrutinizing the Kohn-Sham FMOs.
      The torsional deviation from coplanarity is predominantly influencing the
      electronic structure, i.e., by deviation from ideal overlap and maximal electron
      transmission. The reversible oxidation potentials assigned to the phenothiazinyl
      electrophores in most cases can thereby be qualitatively rationalized. All
      dumbbell-shaped diphenothiazines are strongly luminescent, which can be
      attributed to extended pi-electron conjugation with considerable excited state
      electronic coupling as a consequence of large structural and electronic
      distributional changes upon photoexcitation.

PMID- 21090696
TI  - Detection of organometallic and radical intermediates in the catalytic mechanism
      of methyl-coenzyme M reductase using the natural substrate methyl-coenzyme M and
      a coenzyme B substrate analogue.
AB  - Methyl-coenzyme M reductase (MCR) from methanogenic archaea catalyzes the
      terminal step in methanogenesis using coenzyme B (CoBSH) as the two-electron
      donor to reduce methyl-coenzyme M (methyl-SCoM) to form methane and the
      heterodisulfide, CoBS-SCoM. The active site of MCR contains an essential redox
      active nickel tetrapyrrole cofactor, coenzyme F(430), which is active in the
      Ni(I) state (MCR(red1)). Several catalytic mechanisms have been proposed for
      methane synthesis that mainly differ in whether an organometallic methyl-Ni(III)
      or a methyl radical is the first catalytic intermediate. A mechanism was recently
      proposed in which methyl-Ni(III) undergoes homolysis to generate a methyl radical
      (Li, X., Telser, J., Kunz, R. C., Hoffman, B. M., Gerfen, G., and Ragsdale, S. W.
      (2010) Biochemistry 49, 6866-6876). Discrimination among these mechanisms
      requires identification of the proposed intermediates, none of which have been
      observed with native substrates. Apparently, intermediates form and decay too
      rapidly to accumulate to detectible amounts during the reaction between methyl
      SCoM and CoBSH. Here, we describe the reaction of methyl-SCoM with a substrate
      analogue (CoB(6)SH) in which the seven-carbon heptanoyl moiety of CoBSH has been
      replaced with a hexanoyl group. When MCR(red1) is reacted with methyl-SCoM and
      CoB(6)SH, methanogenesis occurs 1000-fold more slowly than with CoBSH. By
      transient kinetic methods, we observe decay of the active Ni(I) state coupled to
      formation and subsequent decay of alkyl-Ni(III) and organic radical intermediates
      at catalytically competent rates. The kinetic data also revealed substrate
      triggered conformational changes in active Ni(I)-MCR(red1). Electron paramagnetic
      resonance (EPR) studies coupled with isotope labeling experiments demonstrate
      that the radical intermediate is not tyrosine-based. These observations provide
      support for a mechanism for MCR that involves methyl-Ni(III) and an organic
      radical as catalytic intermediates. Thus, the present study provides important
      mechanistic insights into the mechanism of this key enzyme that is central to
      biological methane formation.

PMID- 21090697
TI  - Orientational order of colloidal disk-shaped particles under shear-flow
      conditions: a rheological-small-angle X-ray scattering study.
AB  - The structure of a colloidal dispersion consisting of anisometric natural clay
      particles (beidellite) was followed under shear-flow conditions by small-angle X
      ray scattering (SAXS) measurements in a Couette-type cell. It is shown that in
      this shear-thinning dispersion an orientational order develops with increasing
      shear rate. By use of two different geometrical configurations for SAXS
      measurements, corresponding to incident beam parallel and perpendicular to flow
      velocity gradient (radial and tangential configurations, respectively), it is
      observed that SAXS patterns are anisotropic in both geometries, meaning that
      particles tend to align along a preferred orientation with their normal in
      velocity gradient direction, and further they partly rotate around flow
      streamlines. Quantitative interpretation of these results is successfully
      achieved upon derivation of a probability distribution function accounting for
      biaxial particle orientation. From this distribution and following geometrical
      arguments, the viscosity of the suspension was calculated for each shear rate and
      found to correctly compare with rheological measurements, thereby appropriately
      relating the anisotropy of the SAXS patterns to macroscopic flow behavior of the
      suspension.

PMID- 21090698
TI  - Radical chemistry of 8-oxo-7,8-dihydro-2'-deoxyadenosine and 8-oxo-7,8-dihydro-2'
      deoxyguanosine: a pulse radiolysis study.
AB  - The reactions of oxidizing ((*)OH, N(3)(*), and SO(4)(*-)) and reducing (e(aq)(
      )) radicals with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) and 8-oxo-7,8
      dihydro-2'-deoxyadenosine (8-oxoA) have been studied by pulse radiolysis to
      elucidate the initial free radical processes in their oxidation since these
      oxidized purines are readily oxidized in DNA. The second-order rate constants for
      the reaction of the (*)OH with 8-oxoA and 8-oxoG were determined to be 4.3 *
      10(9) and 4.8 * 10(9) dm(3) mol(-1) s(-1), respectively. Similar values were also
      obtained with the N(3)(*) radical, the respective values being 8.8 * 10(9) and
      3.8 * 10(9) dm(3) mol(-1) s(-1). The transient absorption spectrum following
      reaction of 8-oxoA with (*)OH is assigned to the C4- and C5-OH adducts which then
      undergo dehydration (k = 5.1 * 10(3) s(-1)) to give a reducing neutral N-centered
      radical. 8-oxoG, on the other hand, either reacts by H abstraction from the amino
      group attached to C2, which undergoes fast tautomerization or the resulting (*)OH
      adduct which rapidly dehydrates (k > 1.7 * 10(6) s(-1)) to give the species
      corresponding to the one-electron oxidized product. The transient absorption
      spectrum measured for the reaction of the N(3)(*) with 8-oxoG is identical to
      that obtained with the (*)OH at pH 10. The rate determining step is the formation
      of the radical cation which then rapidly loses a proton to form the neutral
      radical. It is estimated that 85% of (*)OH adducts are oxidizing while 13% are
      reducing. The yields of the reducing radicals on reaction of e(aq)(-) with 8-oxoA
      or 8-oxoG amount to ~43 and 77% of the respective yield of e(aq)(-), whereas the
      extent of formation of any oxidizing radicals is <=2%. In summary, radical
      intermediates from 8-oxoA or 8-oxoG and their redox potentials have been
      determined so that 8-oxoA and 8-oxoG, if preformed endogenously, may act as
      primary sinks for oxidized DNA damage if present close to DNA radicals induced
      radiolytically.

PMID- 21090701
TI  - Physicochemical properties and activity coefficients at infinite dilution for
      organic solutes and water in the ionic liquid 1-decyl-3-methylimidazolium
      tetracyanoborate.
AB  - The activity coefficients at infinite dilution gamma(13)(infinity) and gas-liquid
      partition coefficients K(L) for 43 solutes-alkanes, alkenes, alkynes,
      cycloalkanes, aromatic hydrocarbons, alcohols, carboxylic acids, thiophene,
      ethers, ketones, and water-in the ionic liquid 1-decyl-3-methylimidazolium
      tetracyanoborate ([dmim][TCB]) were determined by gas-liquid chromatography at
      temperatures from 318.15 to 378.15 K. The partial molar excess Gibbs energies
      DeltaG(1)(E,infinity), enthalpies DeltaH(1)(E,infinity), and entropies
      DeltaS(1)(E,infinity) at infinite dilution were calculated from the experimental
      gamma(13)(infinity) values obtained over the temperature range. Additionally, the
      densities for investigated ionic liquid over the temperature range were
      determined. The selectivities for the aliphatic/aromatic hydrocarbon separation
      problem were calculated from gamma(13)(infinity) and compared to the literature
      values for N-methyl-2-pyrrolidinone (NMP) and sulfolane. It was found that the
      investigated [dmim][TCB] ionic liquid shows much higher capacity than NMP and
      sulfolane and selectivity on the same level as NMP and lower than that for
      sulfolane for the separation of aliphatic hydrocarbons from aromatic
      hydrocarbons.

PMID- 21090700
TI  - Duboscic acid: a potent alpha-glucosidase inhibitor with an unprecedented
      triterpenoidal carbon skeleton from Duboscia macrocarpa.
AB  - Duboscic acid (1), a triterpenoid with a unique carbon backbone, was isolated
      from Duboscia macrocarpa Bocq. It is the first member of a new class of
      triterpenoids, for which the name "dubosane" is proposed. Duboscic acid has a
      potent alpha-glucosidase inhibition, and its structure was unambiguously deduced
      by a single-crystal X-ray diffraction study.

PMID- 21090699
TI  - Analysis of acrolein-derived 1,N2-propanodeoxyguanosine adducts in human
      leukocyte DNA from smokers and nonsmokers.
AB  - Cigarette smoking is a major source of human exposure to acrolein, a widespread
      environmental pollutant and toxicant that is also formed endogenously through
      metabolism of amino acids and polyamines and lipid peroxidation. Acrolein reacts
      with DNA, producing two pairs of regioisomeric 1,N(2)-propanodeoxyguanosine
      adducts: (6R/S)-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2
      a]purine-10(3H)one (alpha-OH-Acr-dGuo) and (8R/S)-3-(2'-deoxyribos-1'-yl)-5,6,7,8
      tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)one (gamma-OH-Acr-dGuo). Previous
      studies indicate that these adducts might be involved in producing mutations in
      the p53 tumor suppressor gene, as observed in lung tumors in smokers, but there
      are only limited published data comparing acrolein-DNA adducts in smokers and
      nonsmokers. In this study, we developed a liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to analyze Acr-dGuo
      adducts in human leukocyte DNA. The potential for artifactual formation was found
      in two steps of the assay: DNA isolation and DNA hydrolysis. This was eliminated
      by employing a Ficoll-Hypaque double density gradient to obtain leukocytes free
      of erythrocyte contamination and by adding glutathione to scavenge acrolein
      present in H(2)O. The accuracy and precision of the method were confirmed. Acr
      dGuo adducts were analyzed in leukocyte DNA from 25 smokers and 25 nonsmokers.
      gamma-OH-Acr-dGuo was the predominant isomer in all samples, while alpha-OH-Acr
      dGuo was detected in only three subjects. There was no significant difference
      between the total Acr-dGuo levels in smokers (7.4 +/- 3.4 adducts/10(9)
      nucleotides) and nonsmokers (9.8 +/- 5.5 adducts/10(9) nucleotides). Although our
      study is limited in size, these results, together with the results of previous
      analyses of acrolein-derived mercapturic acids in the urine of smokers and
      nonsmokers, suggest that glutathione conjugation effectively removes acrolein
      from external exposures such as cigarette smoking, protecting leukocyte DNA from
      damage.

PMID- 21090702
TI  - Influence of protein environment on the electron paramagnetic resonance
      properties of flavoprotein radicals: a QM/MM study.
AB  - The neutral and anionic semiquinone radicals of the flavin adenine dinucleotide
      (FAD) cofactor noncovalently bound in glucose oxidase from A. niger are examined
      with the aid of QM/MM molecular modeling methods, enabling complete inclusion of
      the protein environment. Recently, the electron paramagnetic resonance (EPR)
      characteristics, the anisotropic g tensor and all the significant hyperfine
      couplings, of these flavoprotein radicals were determined at high resolution (J.
      Phys. Chem. B 2008, 112, 3568). A striking difference between the neutral and
      anionic radical forms was found to be a shift in the g(y) principal value. Within
      the QM/MM framework, geometry optimization and molecular dynamics simulations are
      combined with EPR property calculations, employing a recent implementation by
      some of the authors in the CP2K software package. In this way, spectroscopic
      characteristics are computed on the fly during the MD simulations of the solvated
      protein structure, mimicking as best as possible the experimental conditions. The
      general agreement between calculated and experimental EPR properties is
      satisfactory and on par with those calculated with other codes (Gaussian 03,
      ORCA). The protonation state of two histidines (His559 and His516) at the
      catalytic site of this flavoprotein is found to have a remarkable influence on
      the isotropic hyperfine coupling of one of the methyl groups on the neutral FAD
      radical, which is consistent with experimental findings in other flavoproteins
      (J. Biol. Chem. 2007, 282, 4738). Furthermore, the shift in the g(y) principal
      values between the neutral and anionic radicals is well reproduced by QM/MM
      simulations. Incorporation of at least the nearest protein environment of the
      cofactor radicals proves to be vital for a correct reproduction, indicating that
      this shift is a global feature of the protein rather than a local one. In
      addition, QM/MM techniques are used to make a prediction of relative angles
      between important spectroscopic principal directions, which are not readily
      determined by conventional EPR experiments. Significantly, the directions of the
      g(x) and the g(y) components of the g-tensor that lie in the plane of the
      isoalloxazine moiety are rotated by approximately 59 degrees  between the neutral
      and the anionic radicals.

PMID- 21090703
TI  - Nanofibers from blends of polyvinyl alcohol and polyhydroxy butyrate as potential
      scaffold material for tissue engineering of skin.
AB  - Nanofibers were prepared by electrospinning from pure polyvinyl alcohol (PVA),
      polyhydroxybutyrate (PHB), and their blends. Miscibility and morphology of both
      polymers in the nanofiber blends were studied by Fourier transform infrared
      spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and differential scanning calorimetry (DSC), revealing that PVA
      and PHB were miscible with good compatibility. DSC also revealed suppression of
      crystallinity of PHB in the blend nanofibers with increasing proportion of PVA.
      The hydrolytic degradation of PHB was accelerated with increasing PVA fraction.
      Cell culture experiments with a human keratinocyte cell line (HaCaT) and dermal
      fibroblast on the electrospun PHB and PVA/PHB blend nanofibers showed maximum
      adhesion and proliferation on pure PHB. However, the addition of 5 wt % PVA to
      PHB inhibited growth of HaCaT cells but not of fibroblasts. On the contrary,
      adhesion and proliferation of HaCaT cells were promoted on PVA/PHB (50/50)
      fibers, which inhibited growth of fibroblasts.

PMID- 21090704
TI  - On the use of excess entropy scaling to describe single-molecule and collective
      dynamic properties of hydrocarbon isomer fluids.
AB  - We use molecular simulation to study the ability of excess entropy scaling
      relationships to describe the kinetic properties of four hydrocarbon isomers: n
      octane, 2,2-dimethylhexane, 2,5-dimethylhexane, and 3-methyl-3-ethylpentane. Four
      dynamic properties are considered: translational and rotational diffusivities, a
      characteristic relaxation time for rotational motion, and a collective relaxation
      time stemming from analysis of the coherent intermediate scattering function. For
      each of the dynamic properties considered, reduced data collapse onto a species
      specific common curve when expressed as a function of the thermodynamic excess
      entropy. Because each isomer exhibits a quantitatively distinct excess entropy
      scaling relationship, straightforward corresponding states principles do not
      provide an effective means to predict dynamic properties.

PMID- 21090705
TI  - NHC-catalyzed spiro bis-indane formation via domino Stetter-aldol-Michael and
      Stetter-aldol-aldol reactions.
AB  - Two novel domino NHC-catalyzed spirocyclizations are described herein, enabling
      the rapid construction of three new carbon-carbon bonds and a quaternary center
      with high diastereoselectivity. A variety of spiro bis-indane structures are
      assembled in a single step from simple o-phthaldialdehyde derivatives.

PMID- 21090706
TI  - Structural properties of 1-alkyl-3-methylimidazolium
      bis{(trifluoromethyl)sulfonyl}amide ionic liquids: X-ray diffraction data and
      molecular dynamics simulations.
AB  - X-ray diffraction data for 1-alkyl-3-methylimidazolium
      bis{(trifluoromethyl)sulfonyl}amides are reported as a function of the length of
      the alkyl chain on the imidazolium ring. The measured diffraction patterns have
      been compared with the theoretical patterns calculated (from the geometries
      obtained) with molecular dynamics simulations. This provides a detailed
      description (at the atomistic level) of the morphology in the liquid state of
      these salts, highlighting the role played by the alkyl chain length. An analysis
      of the behavior of the hydrogen bonds that are formed between the imidazolium
      acidic protons and the anion is presented.

PMID- 21090707
TI  - Determination of protein surface hydration shell free energy of water motion:
      theoretical study and molecular dynamics simulation.
AB  - Water on protein surface plays a crucial role in the mechanistic aspects of
      biological processes; principally, this is characterized into two kinds of water
      molecules, biological water and bulk water. As compared to pure water, many
      aspects of the dynamics and structure of the surrounding water near the protein
      surface are much less understood. Evidence shows that those properties of the
      surrounding water induced by the presence of the biological systems differ from
      those of bulk water and that water has low mobility in the hydration shell. An
      intriguing question remains as to how to make a quantitative estimate of the
      hydration shell free energy when there is interaction between the protein and the
      hydration water. To explore this problem, we perform molecular dynamics
      simulation of the water motion in the hydration shell with respect to bulk water.
      A fractional Brownian motion theory combined with numerical simulation and a
      molecular dynamics simulation was developed. This theory was used to directly
      establish the connection between the dynamics of the protein surface water motion
      and the interaction between water and protein; this offers the possibility of
      determining the hydration shell free energy. In this study, we focused on water
      motion at the protein surface that is within a 4.4 A layer, which is referred to
      as the hydration shell. We demonstrate that it actually follows a fractional
      Brownian motion. In this regime, a developed fractional Fokker-Planck equation,
      which is used to describe the dynamics of protein surface water motion, permits
      us to solve the mean first passage time of water molecules through the hydration
      shell. We then estimate the protein surface hydration shell free energy (HSFE),
      which depends on the barrier height of the hydration shell. For myoglobin, its
      HSFE is about 1.73 kcal/mol, and the accompanying activation entropy is 1.40R,
      where R is the gas constant. Corresponding reduced water mobility is observed for
      water surrounding myoglobin. In accord with the analysis of the radial
      distribution function, it is revealed that the effect of temperature on the HSFE
      is weak. The results show that the protein surface is wrapped by a shell of low
      mobility water motion and this hydration shell is dynamic rather than static.

PMID- 21090708
TI  - Compound ES of dehaloperoxidase decays via two alternative pathways depending on
      the conformation of the distal histidine.
AB  - Dehaloperoxidase (DHP) is a respiratory hemoglobin (Hb) that has been shown to
      catalyze the conversion of trihalophenols to dihaloquinones in the presence of
      hydrogen peroxide. Ferric heme states of the resting DHP and the free radical
      intermediates formed under H2O2 treatment were studied by low-temperature
      electron paramagnetic resonance spectroscopy in the range of reaction times from
      50 ms to 2 min at three different pH values. Two high-spin ferric heme forms were
      identified in the resting enzyme and assigned to the open and closed
      conformations of the distal histidine, His55. Two free radicals were found in DHP
      activated by H2O2: the radical associated with Compound ES (the enzyme with the
      heme in the oxoferryl state and a radical on the polypeptide chain) has been
      assigned to Tyr34, and the other radical has been assigned to Tyr38. The Tyr34
      radical is formed with a very high relative yield (almost 100% of heme), atypical
      of other globins. High-performance liquid chromatography analysis of the reaction
      products showed a pH-dependent formation of covalent heme-to-protein cross-links.
      The stable DHP Compound RH, formed under H2O2 in the absence of the trihalophenol
      substrates, is proposed to be a state with the ferric heme covalently cross
      linked to Tyr34. A kinetic model of the experimental data suggests that formation
      of Compound RH and formation of the Tyr38 radical are two alternative routes of
      Compound ES decay. Which route is taken depends on the conformation of His55: in
      the less populated closed conformation, the Tyr38 radical is formed, but in the
      major open conformation, Compound ES decays, yielding Compound RH, a product of
      safe termination of the two oxidizing equivalents of H2O2 when no substrate is
      available.

PMID- 21090709
TI  - Intermediate-valence tautomerism in decamethylytterbocene complexes of methyl
      substituted bipyridines.
AB  - Multiconfigurational, intermediate valent ground states are established in
      several methyl-substituted bipyridine complexes of
      bis(pentamethylcyclopentadienyl)ytterbium, Cp2*Yb (Me(x)-bipy). In contrast to
      Cp2*Yb(bipy) and other substituted-bipy complexes, the nature of both the ground
      state and the first excited state are altered by changing the position of the
      methyl or dimethyl substitutions on the bipyridine rings. In particular, certain
      substitutions result in multiconfigurational, intermediate valent open-shell
      singlet states in both the ground state and the first excited state. These
      conclusions are reached after consideration of single-crystal X-ray diffraction
      (XRD), the temperature dependence of X-ray absorption near-edge structure
      (XANES), extended X-ray absorption fine-structure (EXAFS), and magnetic
      susceptibility data, and are supported by CASSCF-MP2 calculations. These results
      place the various Cp2*Yb(bipy) complexes in a new tautomeric class, that is,
      intermediate-valence tautomers.

PMID- 21090710
TI  - Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by
      molecular dynamics simulations.
AB  - siRNA and microRNA (miRNA) are two classes of noncoding RNAs that carry out post
      transcriptional gene regulation by interacting with the target mRNA. The
      structural features of siRNA/miRNA-mRNA complex play a crucial role in gene
      silencing. Here we have used computer modeling and simulation approach to (i)
      elucidate the possible structures of the partially complementary lin-4:lin-14
      miRNA-mRNA complex and (ii) compare the structural features with the fully
      complementary lin-4:lin-14 siRNA-mRNA complex. The fully complementary siRNA
      complex maintains a canonical helical shape while the presence of mismatch base
      pairs and bulge induce a kinked structure in the miRNA complex. Docking of the
      simulated duplex models on to the argonaute protein gives a direct indication
      that in the siRNA-mRNA structure, the scissile phosphate of the mRNA strand is
      more accessible to the catalytic site as compared to the miRNA-mRNA structures,
      providing an explanation for the less prevalence of the cleavage in the later
      case.

PMID- 21090712
TI  - Tunable chiral reaction media based on two-component liquid crystals: regio-,
      diastereo-, and enantiocontrolled photodimerization of anthracenecarboxylic
      acids.
AB  - Three kinds of enantiopure amphiphilic amino alcohols (1a-c) were newly
      synthesized, of which the stereochemistry of the stereogenic carbons adjacent to
      the amino (C2) and hydroxy (C1) groups was systematically varied. By using these
      amino alcohols and four photoreactive carboxylic acids, 12 kinds of salts were
      prepared. The structure and thermal behavior of the salts were thoroughly
      investigated by various techniques, which revealed that the stereochemistry of
      the amino alcohol unit has significant effects on the properties of the salts;
      the salts of 1a with (1R,2S)-configuration did not exhibit any liquid crystal
      (LC) phase but showed high crystallinity, whereas 1b and 1c with (1S,2S)- and
      (1S)-configurations, respectively, generally afforded stable LC salts with
      smectic structure(s). Within the matrix of these amphiphilic salts, the in situ
      photodimerizations of 2-anthracenecarboxylic acid (2c) and 1-anthracenecarboxylic
      acid (2d) were conducted by the irradiation with UV/vis light (500 W, a high
      pressure mercury arc lamp, >380 nm). Concerning reactivity and regio-/diastereo
      /enantioselectivities, the LC phases were found to be superior to isotropic and
      crystalline phases. For the two substrates 2c and 2d, every LC phase promoted the
      photodimerization with unprecedentedly high head-to-head selectivity.
      Particularly in the case of 2c, diastereoselecitivity (syn(HH) vs anti(HH)) could
      be rationally controlled by the choice of the amino alcohol unit and mesophase
      (syn(HH):anti(HH) = 61:37 to 26:72). Moreover, one of the LC phases exhibited by
      1b.2c afforded the anti(HH)-dimer of 2c with excellent enantioselectivity (up to
      86% ee). On the basis of the hypothesis that the present photochemical outcome
      arises from the preorientation of the substrates, a preliminary structural model
      of these LCs was proposed.

PMID- 21090711
TI  - Fabrication of ordered nanostructures of sulfide nanocrystal assemblies over self
      assembled genetically engineered P22 coat protein.
AB  - Ordered ZnS and CdS nanocrystal assemblies have been synthesized by a facile
      bioinspired approach consisting of an initial self-assembly of engineered
      proteins into spherical biotemplates and a subsequent protein-directed nucleation
      and growth of ZnS and CdS nanocrystals symmetrically distributed over the self
      assembled biotemplates.

PMID- 21090713
TI  - Anisotropic ionic conductivity in block copolymer membranes by magnetic field
      alignment.
AB  - The self-assembly of diblock copolymers provides a convenient route to the
      formation of mechanically robust films with precise and tunable periodic
      arrangements of two physically demixed but chemically linked polymeric materials.
      Chemoselective transport membranes may be realized from such films by selective
      partitioning of an active species into one of the polymer domains. Here, lithium
      ions were selectively sequestered within the poly(ethylene oxide) block of a
      liquid crystalline diblock copolymer to form polymer electrolyte membranes.
      Optimization of the membrane conductivity mandates alignment of self-assembled
      structures such that conduction occurs via direct as opposed to tortuous
      transport between exterior surfaces. We show here that magnetic fields can be
      used in a very simple and scalable manner to produce highly aligned hexagonally
      packed cylindrical microdomains in such membranes over macroscopic areas. We
      systematically explore the dependence of the ionic conductivity of the membrane
      on both temperature and magnetic field strength. A surprising order of magnitude
      increase in conductivity relative to the nonaligned case is found in films
      aligned at the highest magnetic field strengths, 6 T. The conductivity of field
      aligned samples shows a nonmonotonic dependence on temperature, with a marked
      decrease on heating in the proximity of the order-disorder transition of the
      system before increasing again at elevated temperatures. The data suggest that
      domain-confined transport in hexagonally packed cylindrical systems differs
      markedly in anisotropy by comparison with lamellar systems.

PMID- 21090714
TI  - Gas sensing with high-resolution localized surface plasmon resonance
      spectroscopy.
AB  - We report the first inert gas sensing and characterization studies based on high
      resolution localized surface plasmon resonance (HR-LSPR) spectroscopy. HR-LSPR
      was used to detect the extremely small changes (<3 * 10(-4)) in bulk refractive
      index when the gas was switched between He(g) and Ar(g) or He(g) and N2(g). We
      also demonstrate submonolayer sensitivity to adsorbed water from exposure of the
      sensor to air (40% humidity) versus dry N2(g). These measurements significantly
      expand the applications space and characterization tools for plasmonic
      nanosensors.

PMID- 21090715
TI  - Ca2LiC3H: a new complex carbide hydride phase grown in metal flux.
AB  - The reaction of carbon and CaH2 in a calcium/lithium flux mixture produces
      crystals of the new compound Ca2LiC3H. This phase forms with a new structure type
      in tetragonal space group P4/mbm (a = 6.8236(1) A, c = 3.7518(1) A, Z = 2, R1 =
      0.0151). This is a stuffed variant of the Cs2(NH2)N3 structure, containing
      hydride anions in octahedral sites; the structure determination by single-crystal
      X-ray diffraction surprisingly allowed the hydrogen to be detected. The Ca2LiC3H
      structure also features the rarely seen C3(4-) carbide anion; the protolysis
      reaction of this compound with ammonium chloride produces C3H4. The electronic
      properties of Ca2LiC3H were studied by quantum-chemical calculations including
      band structure and electron localization function (ELF) analysis; the phase is a
      charge-balanced semiconductor with a calculated band gap of 0.48 eV. This is in
      agreement with (7)Li, (13)C, and (1)H MAS NMR data, which show resonances in the
      ionic region instead of the Knight shifted region. ELF analysis of the
      theoretical nonhydrided Ca2LiC3 structure confirms the ability of these
      calculations to properly locate hydrides and supports the structural model based
      on X-ray diffraction data.

PMID- 21090716
TI  - Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid
      arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H
      imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H
      imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932).
AB  - Sphingosine 1-phosphate lyase (S1PL) has been characterized as a novel target for
      the treatment of autoimmune disorders using genetic and pharmacological methods.
      Medicinal chemistry efforts targeting S1PL by direct in vivo evaluation of
      synthetic analogues of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)
      imidazole (THI, 1) led to the discovery of 2 (LX2931) and 4 (LX2932). The
      immunological phenotypes observed in S1PL deficient mice were recapitulated by
      oral administration of 2 or 4. Oral dosing of 2 or 4 yielded a dose-dependent
      decrease in circulating lymphocyte numbers in multiple species and showed a
      therapeutic effect in rodent models of rheumatoid arthritis (RA). Phase I
      clinical trials indicated that 2, the first clinically studied inhibitor of S1PL,
      produced a dose-dependent and reversible reduction of circulating lymphocytes and
      was well tolerated at dose levels of up to 180 mg daily. Phase II evaluation of 2
      in patients with active rheumatoid arthritis is currently underway.

PMID- 21090717
TI  - Protocatechuic acid, a metabolite of anthocyanins, inhibits monocyte adhesion and
      reduces atherosclerosis in apolipoprotein E-deficient mice.
AB  - Polyphenols, including anthocyanins, from various plant foods are effective in
      the prevention of atherosclerosis in animal and human studies. Protocatechuic
      acid (PCA), a major metabolite of anthocyanins, has been found to possess the
      anti-carcinogenic effect, whereas the in vivo effect of PCA as an anti
      atherosclerotic agent remains unknown. We demonstrated herein that PCA inhibited
      monocyte adhesion to tumor necrosis factor-alpha (TNF-alpha)-activated mouse
      aortic endothelial cells, associated with the inhibition of vascular cell
      adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)
      expression. Furthermore, PCA inhibited the nuclear content of p65, a subunit of
      nuclear factor-kappaB (NF-kappaB), along with reduced NF-kappaB binding activity.
      Finally, PCA administration in the apolipoprotein E (ApoE)-deficient mouse model
      reduced aortic VCAM-1 and ICAM-1 expression, NF-kappaB activity, and plasma
      soluble VCAM-1 and ICAM-1 levels, with inhibiting atherosclerosis development. We
      suggest that PCA possesses the anti-atherogenic effect at least partially via its
      anti-inflammatory activity.

PMID- 21090718
TI  - Morphogenetic signaling molecules of the streptomycetes.

PMID- 21090719
TI  - A dual platform for selective analyte enrichment and ionization in mass
      spectrometry using aptamer-conjugated graphene oxide.
AB  - This study demonstrates the use of aptamer-conjugated graphene oxide as an
      affinity extraction and detection platform for analytes from complex biological
      media. We have shown that cocaine and adenosine can be selectively enriched from
      plasma samples and that direct mass spectrometric readouts can be obtained
      without a matrix and with greatly improved signal-to-noise ratios. Aptamer
      conjugated graphene oxide has clear advantages in target enrichment and in
      generating highly efficient ionization of target molecules for mass spectrometry.
      These results demonstrate the utility of the approach for analysis of small
      molecules in real biological samples.

PMID- 21090720
TI  - A new exTTF-crown ether platform to associate fullerenes: cooperative n-pi and pi
      pi effects.
AB  - A new and readily available exTTF-bis(crown ether), 1, efficiently recognizes C60
      as well as C70 by means of cooperative pi-pi and n-pi interactions. The
      geometrical (concave-convex) and electronic (donor-acceptor) complementarity
      accounts on one hand for remarkable binding strengths, with association constants
      reaching 10(7) M(-1) in benzonitrile, and on the other hand for lifetimes of the
      photogenerated radical ion pair state on the order of 45 ps.

PMID- 21090722
TI  - Synthesis of cyclododeciptycene quinones.
AB  - Cycloiptycenes are elusive and synthetically challenging molecules. We report the
      first synthesis of two substituted cyclododeciptycene tetraquinones via a
      sequence of intermolecular and intramolecular Diels-Alder reactions from cis,cis
      heptiptycene tetraquinone 2 and substituted 7,16-dihydro-7,16-(o
      benzeno)heptacenes 3. Heptiptycene tetraquinone 2 was made from triptycene
      bisquinone 4 and 1,4-dimethoxyanthracene in three steps, and 6,8,15,17
      tetramethoxy-7,16-dihydro-7,16-(o-benzeno)heptacene (3a) was synthesized from
      triptycene bisquinone 4 and 1,4-dihydro-2,3-benzoxathiin-3-oxide in four steps.
      The structure of a cyclododeciptycene, 1a, was determined by a single-crystal X
      ray analysis. The synthetic sequence is general and should allow the
      incorporation of various alkoxy and acetoxy substituents appended to the
      cycloiptycene framework.

PMID- 21090721
TI  - NMR solution structure of a DNA-actinomycin D complex containing a non-hydrogen
      bonding pair in the binding site.
AB  - The solution structures of two different DNA duplexes (one containing a G-T
      mismatched base pair and the other a non-hydrogen-bonding G-F pair, where F is
      difluorotoluene) in complex with the peptide antibiotic actinomycin D (ActD) are
      presented. Using (1)H, (19)F NMR, and molecular dynamics simulations, we show
      that there are three major differences between the complexes: (1) ActD binds to
      the GF duplex in an orientation that is flipped 180 degrees  relative to its
      position in the GT duplex; (2) whereas the difluorotoluene moiety takes the
      typical anti glycosidic conformation in the "free" (uncomplexed) GF duplex, it
      takes the syn conformation in the GF:ActD complex; and (3) in GF:ActD, the
      difluorotoluene moiety is completely unstacked in the helix; however, the guanine
      of the G-F pair is stacked quite well with the ActD intercalator and the flanking
      base on the 5' side. In GT:ActD, the G-T base pair (although pushed into the
      major groove from the non-Watson-Crick hydrogen-bonding pattern) stacks favorably
      with the ActD intercalator and the flanking base pair on the 5' side. The results
      described here indicate that a sequence-specific DNA binding ligand such as
      actinomycin D will, indeed, recognize and bind with high affinity to a DNA
      incorporating a non-natural, non-hydrogen-bonding nucleoside mimic despite the
      presentation of modified functionality in the binding site.

PMID- 21090723
TI  - Bodipy dyes with tunable redox potentials and functional groups for further
      tethering: preparation, electrochemical, and spectroscopic characterization.
AB  - The preparation, spectroscopic, and electrochemical characterization of a family
      of 16 new bodipy dyes with tunable redox potentials and versatile functional
      groups is reported. Electron-withdrawing or -donating groups (Et, H, Cl, or CN)
      at positions C2 and C6 enabled tuning the redox potentials within a ca. 0.7 eV
      window without significantly affecting either the HOMO-LUMO gap or the absorption
      and emission spectra. Hydroxymethyl or formyl groups at the meso (C8) position in
      turn provided a handle for covalent tethering to receptors and biomolecules of
      interest, which dispenses with the more commonly used meso-aryl moiety as a means
      to tag molecules. The dyes can thus be coupled to both electrophiles and
      nucleophiles. Importantly, it is shown that meso-formyl bodipy dyes are
      nonemissive and have significantly lower molar extinction coefficients compared
      to their meso-hydroxymethyl and meso-acetoxymethyl counterparts (which in turn
      are bright, with emission quantum yields in the range of 0.7-1). The nonemissive
      meso-formyl bodipy dyes thus provide unique opportunities as fluorogenic probes
      of nucleophilic attack and as fluorescent labeling agents where uncoupled
      fluorophores will not contribute to the fluorescence background. Overall, the new
      bodipy dyes reported here are promising candidates for the preparation of
      fluorescent sensors relying on photoinduced electron transfer and may find use in
      a number of fluorescent-labeling protocols.

PMID- 21090724
TI  - Dependence of electrochemical and electrogenerated chemiluminescence properties
      on the structure of BODIPY dyes. Unusually large separation between sequential
      electron transfers.
AB  - Electrochemistry and electrogenerated chemiluminescence (ECL) of selected
      substituted BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes have been
      studied. The location and nature of substituents on positions 1-8 are important
      in predicting the behavior, and especially the stability, of the radical ions
      formed on electron transfer. Dyes with unsubstituted positions 2, 6, and 8 show a
      kinetic contribution to both oxidation and reduction. Dyes with only
      unsubstituted positions 2 and 6 and a substituted 8 position show chemically
      reversible reduction but irreversible oxidation. Unsubstituted positions 2 and 6
      tend to show dimer formation on oxidation. Completely substituted dyes show
      nernstian oxidation and reduction. Oxidation and reduction studies of simple
      BODIPY dyes show an unusually large separation between the first and second
      reduction peaks and also the first and second oxidation peaks, of about 1.1 V,
      which is very different from that observed for polycyclic hydrocarbons and other
      heteroaromatic compounds, where the spacing is usually about 0.5 V. Electronic
      structure calculations confirmed this behavior, and this effect is attributed to
      a greater electronic energy required to withdraw or add a second electron and a
      lower relative solvation energy for the dianion or dication compared with those
      of the polycyclic hydrocarbons. ECL was generated for all compounds either by
      annihilation or by using a co-reactant.

PMID- 21090725
TI  - Effects of salt on the lower critical solution temperature of poly (N
      isopropylacrylamide).
AB  - Classical molecular dynamics simulations were performed to investigate the
      effects of salt on the lower critical solution temperature (LCST) of Poly (N
      isopropylacrylamide) (PNIPAM). PNIPAM is often studied as a protein proxy due to
      the presence of a peptide bond in its monomer unit. PNIPAM is a temperature
      sensitive polymer which exhibits hydrophobic-hydrophilic phase transition at its
      LCST. The presence of salt in the solution will shift its LCST, typically to a
      lower temperature. This LCST shift follows the so-called Hofmeister series.
      Molecular dynamics (MD) simulations of PNIPAM in 1 M of NaCl, NaBr, NaI, and KCl
      were carried out to elucidate the effects of different salt on LCST and protein
      stability. Our results suggest that direct interactions between the salt cations
      and the polymer play a critical role in the shift of LCST and subsequently on
      protein stability. Further, cations have a much stronger affinity with the
      polymer, whereas anions bind weakly with the polymer. Moreover, the cation
      polymer binding affinity is inversely correlated with the cation-anion contact
      pair association constant in solution.

PMID- 21090726
TI  - Modeling the interactions of the nucleotide excision repair UvrA(2) dimer with
      DNA.
AB  - The UvrA protein initiates the DNA damage recognition process by the bacterial
      nucleotide excision repair (NER) system. Recently, crystallographic structures of
      holo-UvrA(2) dimers from two different microorganisms have been released (Protein
      Data Bank entries 2r6f , 2vf7 , and 2vf8 ). However, the details of the DNA
      binding by UvrA(2) and other peculiarities involved in the damage recognition
      process remain unknown. We have undertaken a molecular modeling approach to
      appraise the possible modes of DNA-UvrA(2) interaction using molecular docking
      and short-scale guided molecular dynamics [continuum field, constrained, and/or
      unrestricted simulated annealing (SA)], taking into account the three-dimensional
      location of a series of mutation-identified UvrA residues implicated in DNA
      binding. The molecular docking was based on the assumptions that the UvrA(2)
      dimer is preformed prior to DNA binding and that no major protein conformational
      rearrangements, except moderate domain reorientations, are required for binding
      of undamaged DNA. As a first approximation, DNA was treated as a rigid ligand.
      From the electrostatic relief of the ventral surface of UvrA(2), we initially
      identified three, noncollinear DNA binding paths. Each of the three resulting
      nucleoprotein complexes (C1, C2, and C3) was analyzed separately, including
      calculation of binding energies, the number and type of interaction residues
      (including mutated ones), and the predominant mode of translational and
      rotational motion of specific protein domains after SA to ensure improved DNA
      binding. The UvrA(2) dimer can accommodate DNA in all three orientations, albeit
      with different binding strengths. One of the UvrA(2)-DNA complexes (C1) fulfilled
      most of the requirements (high interaction energy, proximity of DNA to mutated
      residues, etc.) expected for a natural, high-affinity DNA binding site. This
      nucleoprotein presents a structural organization that is designed to clamp and
      bend double-stranded DNA. We examined the binding site in more detail by docking
      DNAs of significantly different (AT- vs CG-enriched) sequences and by submitting
      the complexes to DNA-unrestricted SA. It was found that in a manner independent
      of the DNA sequence and applied MD protocols, UvrA(2) favors binding of a bent
      and unwound undamaged DNA, with a kink positioned in the proximity of the Zn3
      hairpins, anticollinearly aligned at the bottom of the ventral protein surface.
      It is further hypothesized that the Zn3 modules play an essential role in the
      damage recognition process and that the apparent existence of a family of DNA
      binding sites might be biologically relevant. Our data should prove to be useful
      in rational (structure-based) mutation studies.

PMID- 21090727
TI  - Izumiphenazines A-C: isolation and structure elucidation of phenazine derivatives
      from Streptomyces sp. IFM 11204.
AB  - Three new phenazine derivatives, named izumiphenazines A-C (1-3), and the known
      phenazine-1,6-dicarboxylic acid (4) were isolated from Streptomyces sp. IFM
      11204. The structures of the isolated compounds were elucidated by means of
      spectroscopic methods including UV, IR, HRESIMS, and 1D and 2D NMR. Compounds 1-3
      were evaluated for their activity in overcoming TRAIL (TNF-related apoptosis
      inducing ligand) resistance in human gastric adenocarcinoma cells. Compounds 2
      (30 MUM) and 3 (20 MUM) in combination with TRAIL showed synergistic activity in
      sensitizing TRAIL-resistant AGS cells.

PMID- 21090728
TI  - Comprehensive comparison of ligand-based virtual screening tools against the DUD
      data set reveals limitations of current 3D methods.
AB  - In recent years, many virtual screening (VS) tools have been developed that
      employ different molecular representations and have different speed and accuracy
      characteristics. In this paper, we compare ten popular ligand-based VS tools
      using the publicly available Directory of Useful Decoys (DUD) data set comprising
      over 100 000 compounds distributed across 40 protein targets. The DUD was
      developed initially to evaluate docking algorithms, but our results from an
      operational correlation analysis show that it is also well suited for comparing
      ligand-based VS tools. Although it is conventional wisdom that 3D molecular shape
      is an important determinant of biological activity, our results based on
      permutational significance tests of several commonly used VS metrics show that
      the 2D fingerprint-based methods generally give better VS performance than the 3D
      shape-based approaches for surprisingly many of the DUD targets. To help
      understand this finding, we have analyzed the nature of the scoring functions
      used and the composition of the DUD data set itself. We propose that to improve
      the VS performance of current 3D methods, it will be necessary to devise
      screening queries that can represent multiple possible conformations and which
      can exploit knowledge of known actives that span multiple scaffold families.

PMID- 21090729
TI  - Different binding modes of structurally diverse ligands for human D3DAR.
AB  - Five different dopamine D3 receptors (D3DARs) models were created considering
      some suggested binding modes for D3DAR antagonists reported in earlier
      computational studies. Different hypotheses are justified because of the lack of
      experimental information about the putative site of interaction and are also due
      to the variability in scaffolds and size of D3DAR ligands. In this study 114
      potent and selective D3DAR antagonists or partial agonists are used as key
      experimental information to discriminate the most reliable receptor model and to
      build a docking based 3D quantitative structure-activity relationship model able
      to indicate the ligand properties and the residues important for activity. The
      ability of this D3DAR model to discriminate the binding mode of different classes
      of ligands, showing a good quantitative correlation with their activity,
      encourages us to use it for screening novel lead compounds.

PMID- 21090731
TI  - Predissociation via conformational change: photodissociation of N,N
      dimethylnitrosamine in the S(1) state.
AB  - We investigated the photodissociation mechanism of N,N-dimethylnitrosamine
      (CH(3))(2)NNO (DMN) by ab intio quantum chemical methods. Inspired by an earlier
      study we calculated two-dimensional potential energy surfaces of the S(1) state
      of DMN in its planar and pyramidal conformations. While the planar molecular
      geometry appears to possess no direct dissociation channel, the pyramidal
      configuration is dissociative yielding the products NO + (CH(3))(2)N. Using wave
      packet dynamics on the planar S(1) potential energy surface the experimental
      absorption spectrum was well reproduced which gives indirect but strong support
      for the nondissociative nature of this surface. The transition from the planar to
      the pyramidal conformation of DMN was then investigated by an ab initio molecular
      dynamics method which revealed the time evolution of the geometrical parameters
      of the molecule up to the dissociation of the N-N bond. This occurs about 90 fs
      after photon excitation. The calculated minimum energy path along the N-N
      coordinate and the structural changes of the molecule along this coordinate
      provided a detailed picture of this indirect dissociation or, more specific,
      predissociation process via conformational change.

PMID- 21090730
TI  - Synthesis of oxazolo[4,5-c]quinoline TRPV1 antagonists.
AB  - An efficient synthesis of 2-amino-oxazolo[4,5-c]quinoline TRPV1 antagonists is
      described via a thiourea formation/carbodiimide cyclization sequence. Synthetic
      route optimization eliminates intermediate isolations and facilitates the rapid
      preparation of a series of novel pentacyclic TRPV1 antagonists. From this series,
      compound (S)-4 was identified as a potent and selective ligand for the TRPV1 ion
      channel.

PMID- 21090732
TI  - Dielectric spectroscopy of a nanofiltration membranes-electrolyte solution
      system: I. Low-frequency dielectric relaxation from the counterion polarization
      in pores and model development.
AB  - The dielectric spectra of nanofiltration membranes NF90, NF-, and NF270 in eight
      electrolytes, NaCl, KCl, CuCl(2), MgCl(2), Na(2)SO(4), K(2)SO(4), MgSO(4), and
      CuSO(4), were investigated as a function of the electrolyte concentration over a
      frequency range from 40 Hz to 11 MHz. Two relaxations were observed: the one at
      high frequency was caused by interfacial polarization between the membrane and
      electrolyte, and the low-frequency relaxation, on which we focus on in this work,
      was confirmed to be due to the counterion polarization effects in the pores of
      the membrane. A model of cylindrical pores which were dispersed in membrane base
      was developed to interpret the low-frequency relaxation. On the basis of this
      model, we amended the expression deduced by Takashima for describing the
      dielectric behavior of a cylinder particle suspension to fit our dielectric data
      from the low-frequency relaxation. The data fitting with this improved expression
      was suitable for all the systems measured in this work; structural and electrical
      parameters such as the radius of the pore in the membrane, the thickness of the
      active layer of the membrane, surface charged density, and zeta potential on the
      pore wall were obtained finally.

PMID- 21090733
TI  - Single-shot gradient-assisted photon echo electronic spectroscopy.
AB  - Two-dimensional electronic spectroscopy (2D ES) maps the electronic structure of
      complex systems on a femtosecond time scale. While analogous to multidimensional
      NMR spectroscopy, 2D optical spectroscopy differs significantly in its
      implementation. Yet, 2D Fourier spectroscopies still require point-by-point
      sampling of the time delay between two pulses responsible for creating quantum
      coherence among states. Unlike NMR, achieving the requisite phase stability at
      optical frequencies between these pulse pairs remains experimentally challenging.
      Nonetheless, 2D optical spectroscopy has been successfully demonstrated by
      combining passive and active phase stabilization along with precise control of
      optical delays and long-term temperature stability, although the widespread
      adoption of 2D ES has been significantly hampered by these technical challenges.
      Here, we exploit an analogy to magnetic resonance imaging (MRI) to demonstrate a
      single-shot method capable of acquiring the entire 2D spectrum in a single laser
      shot using only conventional optics. Unlike point-by-point sampling protocols
      typically used to record 2D spectra, this method, which we call GRadient-Assisted
      Photon Echo (GRAPE) spectroscopy, largely eliminates phase errors while reducing
      the acquisition time by orders of magnitude. By incorporating a spatiotemporal
      encoding of the nonlinear polarization along the excitation frequency axis of the
      2D spectrum, GRAPE spectroscopy achieves no loss in signal while simultaneously
      reducing overall noise. Here, we describe the principles of GRAPE spectroscopy
      and discuss associated experimental considerations.

PMID- 21090734
TI  - Charge separation from the bursting of bubbles on water.
AB  - Film droplets formed from the bursting of 2.4 mm diameter bubbles on the surface
      of pure water are predominantly negatively charged. The charge generated per
      bubble varies chaotically; a few bubbles generate more than -3 * 10(6) elementary
      charges (e) but the vast majority generate much less. The average is -5 *
      10(4)e/bubble, and it is not significantly affected by bubbling rate or
      temperature. The charge diminishes with increasing salt concentration and
      vanishes for concentrations above 10(-3) M. We propose a mechanism consistent
      with the observed charge separation. The model relies on the assumption that the
      surface of pure water has a slight excess of hydroxide ions. The charge
      separation results when water with entrained counterions (H(3)O(+)) flows out of
      the thinning film of the bubble cap, leaving behind the excess OH(-) on the
      surface. Addition of salt reduces the Debye length, and the charge separation
      mechanism becomes less effective as the Debye length becomes small compared with
      the film thickness. The excess charge near the surface of pure water is very
      small, around -4 nC/m(2).

PMID- 21090736
TI  - Top leads for swine influenza A/H1N1 virus revealed by steered molecular dynamics
      approach.
AB  - Since March 2009, the rapid spread of infection during the recent A/H1N1 swine
      flu pandemic has raised concerns of a far more dangerous outcome should this
      virus become resistant to current drug therapies. Currently oseltamivir (tamiflu)
      is intensively used for the treatment of influenza and is reported effective for
      2009 A/H1N1 virus. However, as this virus is evolving fast, some drug-resistant
      strains are emerging. Therefore, it is critical to seek alternative treatments
      and identify roots of the drug resistance. In this paper, we use the steered
      molecular dynamics (SMD) approach to estimate the binding affinity of ligands to
      the glycoprotein neuraminidase. Our idea is based on the hypothesis that the
      larger is the force needed to unbind a ligand from a receptor the higher its
      binding affinity. Using all-atom models with Gromos force field 43a1 and explicit
      water, we have studied the binding ability of 32 ligands to glycoprotein
      neuraminidase from swine flu virus A/H1N1. The electrostatic interaction is shown
      to play a more important role in binding affinity than the van der Waals one. We
      have found that four ligands 141562, 5069, 46080, and 117079 from the NSC set are
      the most promising candidates to cope with this virus, while peramivir,
      oseltamivir, and zanamivir are ranked 8, 11, and 20. The observation that these
      four ligands are better than existing commercial drugs has been also confirmed by
      our results on the binding free energies obtained by the molecular mechanics
      Poisson-Boltzmann surface area (MM-PBSA) method. Our prediction may be useful for
      the therapeutic application.

PMID- 21090737
TI  - Fast oxy-cope rearrangements of bis-alkynes: competition with central C-C bond
      fragmentation and incorporation in tunable cascades diverging from a common bis
      allenic intermediate.
AB  - Fast anionic oxy-Cope rearrangements of 1,5-hexadiyn-3,4-olates can be
      incorporated into cascade transformations which rapidly assemble densely
      functionalized cyclobutenes or cyclopentenones via a common bis-allenic
      intermediate. The competition between fragmentation, 4pi-electrocyclic closure,
      and aldol condensation can be efficiently controlled by the nature of the
      acetylenic substituents. The rearrangement of bis-alkynes with two hydroxyl
      substituents opens a conceptually interesting entry in the chemistry of epsilon
      dicarbonyl compounds and suggests a new approach to analogues of
      rocaglamide/aglafolin.

PMID- 21090739
TI  - A concept to tailor electron delocalization: applying QTAIM analysis to phenyl
      terpyridine compounds.
AB  - To gain a deeper understanding of how structural modifications may influence
      photochemical properties of 4'-phenyl-2,2':6',2''-terpyridines, the
      investigations presented here focus on electron delocalization in 4'-phenyl
      2,2':6',2''-terpyridine derivatives and their Ru(II) and Zn(II) complexes. In
      those systems of neighboring aromatic rings the considerable torsion between the
      rings is commonly regarded to be the limiting factor for a well pronounced pi
      conjugation between the rings. A common approach to improve the pi-conjugation is
      to lower the steric hindrance, thus achieving a more planar geometry. Here, we
      present a fundamentally different approach towards enhanced pi-conjugation by
      manipulation of the electronic properties of the pyridine-phenyl (py-ph) bond.
      This is accomplished by introducing various substituents at the phenylene moiety
      or coordinating the terpyridine moiety to transition metal ions. The electron
      delocalization was quantified via the DFT-calculated ellipticity in the bond
      critical point (BCP) of the py-ph bond. This ellipticity can be modified due to
      substituents in the para position of phenylene and via the transition metals
      coordinated to the terpyridine moiety. Changes in electron density distribution
      induced by the substituents and the metal ions are further studied by means of
      intermolecular electron density difference plots. It was shown that a NH(2) group
      in the para position of the phenyl ring as well as the coordination to Ru(II) or
      Zn(II) ions significantly enhances the pi-character of the py-ph bond.
      Surprisingly, an even higher pi-character of the py-ph bond is achieved by
      introducing additional NH(2) groups in ortho position to the py-ph bond, despite
      the increased torsion between pyridine and phenylene. The introduction of other
      substituents (-NO(2), -Br, -CN, -vinyl, -ethynyl) studied within the presented
      work enables an actuation of the electron delocalization between terpyridine and
      phenylene. In doing so, the ellipticity is a concise quantity to characterize
      electron delocalization in the studied systems. Furthermore, the ellipticity in
      the BCP of the py-ph bond is related to the corresponding geometrical properties
      (e.g., bond length and dihedral angle) and to the DFT-calculated HOMO and LUMO
      energies.

PMID- 21090740
TI  - Tautomeric equilibria of 5-fluorouracil anionic species in water.
AB  - It has long been postulated that rare tautomeric or ionized forms of nucleic acid
      bases may play a role in mispair formation. Therefore, ab initio quantum chemical
      investigations on the tautomeric equilibrium in 5-fluorouracil (5FU) and its
      anions (deprotonated from N1, AN1, and from N3, AN3) and their tautomeric forms
      in water were performed. The effect of the water as solvent was introduced using
      solute-solvent clusters (four water molecules). The influence of the water
      molecules on the tautomeric reactions between different forms was considered by
      multiple proton transfer mechanisms. We show that when a water dimer is located
      in the reaction site between the two pairs of N-H and C?O groups, the assistive
      effect of the water molecules is strengthened. All calculations of the solute
      water complexes were carried out at an MP2 level of theory and supplemented with
      correction for higher order correlation terms at CCSD(T) level, using the 6
      31+G(d,p) basis set. The ab initio calculated frequencies and Raman intensities
      of 5FU and its anions AN1, AN3, and dianion are in good agreement with the
      experimental Raman frequencies in aqueous solution at different pH. In order to
      establish the pH-induced structural transformation in the molecule of 5FU,
      further (1)H, (19)F, and (13)C NMR spectra in water solution for pH = 6.9-13.8
      were acquired and the chemical shift alterations were determined as a function of
      pH. On the basis of NMR spectroscopic data obtained for 5FU in aqueous solution
      at alkaline pH, we suggest the existence of a mixture of the anionic tautomeric
      forms predicted by our theoretical calculations.

PMID- 21090741
TI  - Influence of gold nanorod geometry on optical response.
AB  - As noble metal nanoparticles are deployed into increasingly sophisticated
      environments, it is necessary to fully develop our understanding of nanoparticle
      behavior and the corresponding instrument responses. In this paper, we report on
      the optical response of three important gold nanorod configurations under dark
      field and differential interference contrast (DIC) microscopy after first
      establishing their absolute geometries with transmission electron microscopy
      (TEM). The observed longitudinal plasmon wavelengths of single nanorods are
      located at wavelengths consistent with previously developed theory. A dimer is
      shown exhibiting a multipole plasmon at wavelengths that are consistent with the
      dipole plasmon of single nanorods in the sample. DIC can also distinguish a
      single nanorod from a pair of uncoupled nanorods with an interparticle distance
      below the diffraction limit. The experimental observations are consistent with
      simulated DIC images using a DIC point spread function. The findings herein are a
      critical step toward being able to characterize nanorods in dynamic environments
      without the use of electron microscopy.

PMID- 21090743
TI  - Implications of the use of As-rich groundwater for agricultural purposes and the
      effects of soil amendments on as solubility.
AB  - An agricultural site in Segovia province (Spain) contains high levels of arsenic
      (As) of geological origin in its groundwater, which is used intensively for
      irrigation. Crops, irrigation waters, and soils were analyzed to evaluate the
      occurrence of As in this area and its potential impact on the food chain. High As
      mobility was found in the agricultural soils, related to the application of As in
      the irrigation waters (14.8-280 MUg As L(-1)) and the general alkaline and sandy
      character of these soils, which imposes a low capacity for As sorption and
      therefore enhances plant uptake. The use of amendments can also affect the
      solubility of As in these soils. Evidence for this was evaluated based on a study
      of the effect of organic (compost) and inorganic (iron oxides-rich rolling mill
      scale and phosphate fertilizer) amendments. Arsenic solubility in soil and plant
      uptake were high, but not significantly affected by organic matter or phosphate
      addition, while As immobilization was associated with addition of iron oxides
      with the rolling mill scale, although this did not result in a decrease of As
      uptake by the tested plants.

PMID- 21090742
TI  - pH-dependent mineral release and surface properties of cornstraw biochar:
      agronomic implications.
AB  - Surface charge and pH-dependent nutrient release properties of cornstraw biochar
      were examined to elucidate its potential agronomic benefits. Kinetics of element
      release was characterized by rapid H(+) consumption and rapid, pH-dependent P,
      Ca, and Mg release, followed by zero-order H(+) consumption and mineral
      dissolution reactions. Initial K release was not pH-dependent, nor was it
      followed by a zero-order reaction at any pH. Rapid and constant rate P releases
      were significant, having the potential to substitute substantial proportions of P
      fertilizer. K releases were also significant and may replace conventional K
      fertilizers, however, not long-term plant demand. The cation exchange capacity
      (CEC) of the biochar leached with a mild acidic solution increased linearly from
      179 to 888 mmol(c) (kg C)(-1) over a pH range of 4-8, while the anion exchange
      capacity of 154 mmol(c) (kg C)(-1) was constant over the same pH range. Since
      native soil organic constituents have much higher CEC values (average 2800
      mmol(c) (kg C)(-1) at pH 7), improved soil fertility as a result of enhanced
      cation retention by the biochar probably will be favorable only in sandy and low
      organic matter soils, unless surface oxidation during aging significantly
      increases its CEC.

PMID- 21090744
TI  - Flexographically printed fluidic structures in paper.
AB  - This Technical Note demonstrates a simple method based on flexographic printing
      of polystyrene to form liquid guiding boundaries and layers on paper substrates.
      The method allows formation of hydrophobic barrier structures that partially or
      completely penetrate through the substrate. This unique property enables one to
      form very thin fluidic channels on paper, leading to reduced sample volumes
      required in point-of-care diagnostic devices. The described method is compatible
      with roll-to-roll flexography units found in many printing houses, making it an
      ideal method for large-scale production of paper-based fluidic structures.

PMID- 21090745
TI  - Titanium dioxide-based DGT technique for in situ measurement of dissolved
      reactive phosphorus in fresh and marine waters.
AB  - A new diffusive gradients in a thin film (DGT) technique for measuring dissolved
      reactive phosphorus (DRP) in fresh and marine waters is reported. The new method,
      which uses a commercially available titanium dioxide based adsorbent (Metsorb),
      was evaluated and compared to the well-established ferrihydrite-DGT method
      (ferrihydrite cast within the polyacrylamide gel). DGT time-series experiments
      showed that the mass of DRP accumulated by Metsorb and ferrihydrite was linear
      with time when deployed in simple solutions. Both DGT methods showed predictable
      uptake across the pH (4.0-8.3) and ionic strength (0.0001-1 mol L(-1) NaNO(3))
      ranges investigated, and the total capacity of the Metsorb binding phase (~40,000
      ng P) was 2.5-5 times higher than the reported total capacity of the ferrihydrite
      binding phase. The measurement of DRP in synthetic freshwater and synthetic
      seawater by Metsorb-DGT over a 4 day deployment period showed excellent agreement
      with the concentration of DRP measured directly in solution, whereas the
      ferrihydrite-DGT method significantly underestimated (23-30%) the DRP
      concentration in synthetic seawater for deployment times of two days or more.
      Field deployments of Metsorb-DGT samplers with various diffusive layer
      thicknesses allowed accurate measurement of both the diffusive boundary layer
      thickness and DRP concentration in situ. The Metsorb-DGT method performs
      similarly to ferrihydrite-DGT for freshwater measurements but is shown to be more
      accurate than the ferrihydrite method for determining DRP in seawater.

PMID- 21090746
TI  - Quantitative analysis of ginger components in commercial products using liquid
      chromatography with electrochemical array detection.
AB  - For the first time, a sensitive reversed-phase HPLC electrochemical array method
      has been developed for the quantitative analysis of 8 major ginger components
      ([6]-, [8]-, and [10]-gingerol, [6]-, [8]-, and [10]-shogaol, [6]-paradol, and
      [1]-dehydrogingerdione) in 11 ginger-containing commercial products. This method
      was valid with unrivaled sensitivity as low as 7.3-20.2 pg of limit of detection
      and a range of 14.5-40.4 pg for the limit of quantification. The levels of 8
      ginger components in 11 different commercial products were quantified by use of
      this method. The results found that both levels and ratios among the 8 compounds
      vary greatly in commercial products.

PMID- 21090747
TI  - Changes in concentrations of perfluorinated compounds, polybrominated diphenyl
      ethers, and polychlorinated biphenyls in Norwegian breast-milk during twelve
      months of lactation.
AB  - At present, scientific knowledge on depuration rates of persistent organic
      pollutants (POPs) is limited and the previous assumptions of considerable
      reduction of body burdens through breast-feeding have recently been challenged.
      We therefore studied elimination rates of important POPs in nine Norwegian
      primiparous mothers and one mother breast-feeding her second child by collecting
      breast-milk samples (n = 70) monthly from about two weeks to up to twelve months
      after birth. Perfluorinated compounds (PFCs), polybrominated diphenyl ethers
      (PBDEs), hexabromocyclododecane (HBCD), and polychlorinated biphenyls (PCBs) were
      determined in the breast-milk samples. Linear mixed effect models were
      established for selected compounds, and significant decreases in the range of 1.2
      4.7% in breast-milk concentrations per month were observed for a wide range of
      PCBs and PBDEs. For the first time, depuration rates for perfluorooctylsulfonate
      (PFOS) and perfluorooctanoic acid (PFOA) are presented, being 3.8 and 7.8% per
      month, respectively (p < 0.05). The relative amount of the branched PFOS isomers
      in the breast-milk samples was 18% on average (range 6-36%, RSD 30%). There were
      no significant differences in isomer pattern between the mothers, or changes
      during the lactation period. After a year of nursing the breast-milk
      concentrations of PFCs, PBDEs, and PCBs were reduced by 15-94%.

PMID- 21090749
TI  - Effect of molecular weight and concentration of polyethylene glycol on
      physicochemical properties and stability of shellac film.
AB  - The effects of molecular weight and concentration of plasticizer on
      physicochemical properties and stability of shellac films were investigated. Type
      of plasticizer was previously reported to have some effects on the stability of
      shellac films, and polyethylene glycol (PEG) was the plasticizer of choice for
      plasticizing shellac films. In this study, different molecular weights of PEG
      (200, 400 and 4000) were chosen at a concentration of 10% w/w of shellac films.
      Shellac in alcohol was prepared in a free film. The stability of shellac film was
      then performed at 75% RH, 40  degrees C for 3 months. The comparison was made
      between the film with and without plasticizer. Shellac films were then determined
      for acid value, insoluble solid, mechanical properties and water vapor
      permeability coefficient. It was reported that different molecular weights of PEG
      had some influence on physicochemical properties of the shellac films. Among
      different molecular weights of PEG, PEG 400 showed a suitable molecular weight
      that could protect the shellac chain at the carboxylic and hydroxyl groups.
      Therefore, the molecular weight of plasticizer played a crucial role for the
      protective ability at active sites. Further study was performed to investigate
      the effect of concentrations of PEG 400 on the stability. The results
      demonstrated that PEG 400 at a concentration of 10% (w/w) could prevent the
      polymerization process for only 4 months and a significant change of all
      parameters was then reported. However, a higher concentration, 20% (w/w) of PEG
      400, could prolong the stability of shellac for 6 months of study. Therefore, the
      drawback of shellac as a natural polymer in pharmaceutical and food industries
      could be tackled by the appropriate size and concentration of plasticizer.

PMID- 21090748
TI  - Kinetic analysis of the M2 proton conduction of the influenza virus.
AB  - The M2 protein of the flu virus forms a proton selective channel that is
      necessary for viral replication. The channel has a slow rate of conduction but
      attains near perfect selectivity for protons. Many models have been proposed to
      explain the mechanism of proton conduction based on whole cell channel recordings
      and molecular dynamics simulations, but a detailed kinetic analysis of the
      channel activity has not yet been performed. We obtained detailed conduction vs
      pH measurements for M2 and a number of its variants using a sensitive and
      reproducible liposome proton flux assay. The proton transport follows Michaelis
      Menten-like kinetics with two saturation steps: one pseudosaturation at pH ~5.5,
      and another full saturation at pH ~4. The heart of the mechanism is the pore
      lining His37 and Trp41. NMR measurements suggest that histidine and tryptophan
      act in unison to transport protons down the concentration gradient. The log of
      apparent K(m) derived from the kinetics data matches closely to the histidine
      pK(a) and correlates with chemical shift perturbation of the Trp41 gate,
      indicating that histidine protonation and opening of the channel gate are
      synchronized events. Finally, mutagenesis and structural analysis identified key
      residues that affect the rate of conduction.

PMID- 21090750
TI  - Alignment of plate-like particles in a colloidal dispersion under flow in a
      uniform pipe studied by high-energy X-ray diffraction.
AB  - High-energy angle-dispersive X-ray diffraction has been used to study the
      alignment of colloidal suspension of kaolinite particles in water as they flow
      along a pipe. X-rays with energies above 25 keV have a major advantage, as they
      can penetrate through thick samples and walls of containers and permit
      investigation of samples under realistic flow conditions. As an example of the
      method, flow through a circular cross-section pipe with an internal diameter of 5
      mm has been studied: this is typical of industrial applications. The angular
      distribution of intensities of peaks in the diffraction pattern as a function of
      the location of the pipe in the X-ray beam provides information about the
      alignment of particles under flow. Order parameters have been calculated to
      describe the alignment and direction of orientation. It is observed that the
      particles align in the direction of flow with their flat faces parallel to the
      flow. The experimental results are compared with the calculations of the local
      strain rate that help to explain the onset of alignment of the particles.

PMID- 21090751
TI  - Micro total bioassay system for ingested substances: assessment of intestinal
      absorption, hepatic metabolism, and bioactivity.
AB  - Oral medicines and food constituents are absorbed in the intestine and
      metabolized in the liver, after which they exhibit their activity toward a target
      tissue. Micromodels of human tissues were developed to mimic these processes and
      bioactivities. By integrating the micromodels, we realized a micro total bioassay
      system for oral substances; this system comprised a microintestine, microliver,
      and the target components. The microchip was composed of a slide glass and
      polydimethylsiloxane (PDMS) sheets with microchannels fabricated by
      photolithography. Caco-2 cells were cultured in the intestine component, and
      HepG2 cells, in the liver component. The human breast carcinoma MCF-7 cells were
      cultured in the target component, and the activities of anticancer agents and
      estrogen-like substances were successfully assayed. By using this system, the
      overall properties of the ingested cyclophosphamide, epirubicin, 17-beta
      estradiol, and soy isoflavone, i.e., their intestinal absorption, hepatic
      metabolism, and bioactivity toward target cells, could be assayed with operative
      ease. Further, the assay time and cell consumption were reduced compared to those
      in conventional in vitro bioassay systems.

PMID- 21090752
TI  - Homology modeling and screening of new 14alpha-demethylase inhibitor (DMI)
      fungicides based on optimized expression of CYP51 from Ustilago maydis in
      Escherichia coli.
AB  - Ustilago maydis infection is a serious disease affecting corn crops worldwide.
      Sterol 14alpha-demethylase (CYP51) is one of the key enzymes of sterol
      biosynthesis and an effective target of antifungal drugs. To further study the
      interaction between CYP51 and drugs and exploit more specific 14alpha-demethylase
      inhibitor (DMI) fungicides for U. maydis, in this study homology modeling of
      CYP51 from U. maydis (UmCYP51) templated as the eukaryotic orthologues (the human
      CYP51) and screening of new DMI fungicides based on optimized expression were
      carried out for the first time. In addition, XF-113 and ZST-4 were screened by
      analyzing the spectral characteristics between the purified UmCYP51-35 and
      fungicides. These results provide a theoretical basis and new ideas for efficient
      design and development of new antifungal drugs.

PMID- 21090753
TI  - Resistance of beta-casein at the air-water interface to enzymatic cleavage.
AB  - X-ray reflectivity from an air-buffer interfacial beta-casein monomolecular film
      placed on a solution of chymosin (renin) showed unexpectedly slow proteolytic
      cleavage. To understand this, the separate structures of beta-casein and
      chymosin, the presentation of each molecule to the other at the air/liquid
      interface, and that of their mixtures is reported. At the air/solution interface,
      the hydrophobicity of the protein molecules causes orientation and some
      deformation of the conformation. When beta-casein was presented to a chymosin
      monomolecular interfacial film, the chymosin was largely displaced from the
      surface, which was accounted for by the different surfactancy of the two
      molecules at 25  degrees C. There was no observable proteolysis. In the reverse
      experiment, a significant enzymatic degradation and the signature of hydrophobic
      fragments was observed but only at and above an enzyme concentration of 0.015
      mg/mL in the substrate. For comparison, the air/solution interface of premixed
      beta-casein with chymosin in phosphate buffer showed that the film was composed
      of beta-casein proteolytic fragments and chymosin.

PMID- 21090755
TI  - Effect of intermolecular dipole-dipole interactions on interfacial supramolecular
      structures of C3-symmetric hexa-peri-hexabenzocoronene derivatives.
AB  - Two-dimensional (2D) supramolecular assemblies of a series of novel C(3)
      symmetric hexa-peri-hexabenzocoronene (HBC) derivatives bearing different
      substituents adsorbed on highly oriented pyrolytic graphite were studied by using
      scanning tunneling microscopy at a solid-liquid interface. It was found that the
      intermolecular dipole-dipole interactions play a critical role in controlling the
      interfacial supramolecular assembly of these C(3)-symmetric HBC derivatives at
      the solid-liquid interface. The HBC molecule bearing three -CF(3) groups could
      form 2D honeycomb structures because of antiparallel dipole-dipole interactions,
      whereas HBC molecules bearing three -CN or -NO(2) groups could form hexagonal
      superstructures because of a special trimeric arrangement induced by dipole
      dipole interactions and weak hydrogen bonding interactions ([C-H...NC-] or [C
      H...O(2)N-]). Molecular mechanics and dynamics simulations were performed to
      reveal the physics behind the 2D structures as well as detailed functional group
      interactions. This work provides an example of how intermolecular dipole-dipole
      interactions could enable fine control over the self-assembly of disklike pi
      conjugated molecules.

PMID- 21090754
TI  - Isolation, structural assignment, and total synthesis of barmumycin.
AB  - Barmumycin was isolated from an extract of the marine actinomycete Streptomyces
      sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines.
      On the basis of preliminary one- and two-dimensional (1)H and (13)C NMR spectra,
      the natural compound was initially assigned the structure of macrolactone-type
      compound 1, which was later prepared by two different routes. However, major
      spectroscopic differences between isolated barmumycin and 1 led to revision of
      the proposed structure as E-16. On the basis of the synthesis of this new
      compound, and subsequent spectroscopic comparison of it to an authentic sample of
      barmumycin, the structure of the natural compound was indeed confirmed as that of
      E-16.

PMID- 21090756
TI  - Theoretical study of the Bergman cyclization of 2,3-diethynyl-1-nitrotropylium
      ion: formation of a nitroxide radical amenable to EPR detection for biological
      applications.
AB  - We report a DFT study of a Bergman cyclization producing a stable triplet
      nitroxide diradical and monoradical (after H abstraction from an external
      source). The monoradical is predicted to be amenable to detection by EPR methods
      to potentially probe the structure and dynamics of enediyne molecules for drug
      interactions.

PMID- 21090757
TI  - Trigonal bi- and monopyramidal cobalt(II) complexes of a novel guanidine-based
      tripodal ligand.
AB  - The novel ligand DIG(3)tren has three N',N''-diisopropylguanidinyl (DIG)
      moieties. We report on the structures of two cobalt complexes that show how an
      isopropylamino group from each DIG acts as a flap that can either close over the
      metal or rotate away from the metal to open up a site for auxiliary ligand
      binding. Two of the -NH(iPr) flaps are open in pink [Co(DIG(3)tren)(OAc)]OAc (1),
      and each of these flaps provides a hydrogen bond to stabilize acetate binding to
      trigonal bipyrimidal cobalt. The flaps are closed in blue
      [Co(DIG(3)tren)][BPh(4)](2) (2), yielding a rare example of a trigonal
      (mono)pyramidal [ML](2+) ion.

PMID- 21090758
TI  - Quantitative proteomics identify molecular targets that are crucial in larval
      settlement and metamorphosis of Bugula neritina.
AB  - The marine invertebrate Bugula neritina has a biphasic life cycle that consists
      of a swimming larval stage and a sessile juvenile and adult stage. The attachment
      of larvae to the substratum and their subsequent metamorphosis have crucial
      ecological consequences. Despite many studies on this species, little is known
      about the molecular mechanism of these processes. Here, we report a comparative
      study of swimming larvae and metamorphosing individuals at 4 and 24 h
      postattachment using label-free quantitative proteomics. We identified more than
      1100 proteins at each stage, 61 of which were differentially expressed.
      Specifically, proteins involved in energy metabolism and structural molecules
      were generally down-regulated, whereas proteins involved in transcription and
      translation, the extracellular matrix, and calcification were strongly up
      regulated during metamorphosis. Many tightly regulated novel proteins were also
      identified. Subsequent analysis of the temporal and spatial expressions of some
      of the proteins and an assay of their functions indicated that they may have key
      roles in metamorphosis of B. neritina. These findings not only provide molecular
      evidence with which to elucidate the substantial changes in morphology and
      physiology that occur during larval attachment and metamorphosis but also
      identify potential targets for antifouling treatment.

PMID- 21090759
TI  - Proteomics on brefeldin A-treated Arabidopsis roots reveals profilin 2 as a new
      protein involved in the cross-talk between vesicular trafficking and the actin
      cytoskeleton.
AB  - The growing importance of vesicular trafficking and cytoskeleton dynamic
      reorganization during plant development requires the exploitation of novel
      experimental approaches. Several genetic and cell biological studies have used
      diverse pharmaceutical drugs that inhibit vesicular trafficking and secretion to
      study these phenomena. Here, proteomic and cell biology approaches were applied
      to study effects of brefeldin A (BFA), an inhibitor of vesicle recycling and
      secretion, in Arabidopsis roots. The main aim of this study was to obtain an
      overview of proteins affected by BFA, but especially to identify new proteins
      involved in the vesicular trafficking and its cross-talk to the actin
      cytoskeleton. The results showed that BFA altered vesicular trafficking and
      caused the formation of BFA-compartments which was accompanied by differential
      expression of several proteins in root cells. Some of the BFA-up-regulated
      proteins belong to the class of the vesicular trafficking proteins, such as V
      ATPase and reversibly glycosylated polypeptide, while others, such as profilin 2
      and elongation factor 1 alpha, are rather involved in the remodeling of the actin
      cytoskeleton. Upregulation of profilin 2 by BFA was verified by immunoblot and
      live imaging at subcellular level. The latter approach also revealed that
      profilin 2 accumulated in BFA-compartments which was accompanied by remodeling of
      the actin cytoskeleton in BFA-treated root cells. Thus, profilin 2 seems to be
      involved in the cross-talk between vesicular trafficking and the actin
      cytoskeleton, in a BFA-dependent manner.

PMID- 21090760
TI  - Structural defects in graphene.
AB  - Graphene is one of the most promising materials in nanotechnology. The electronic
      and mechanical properties of graphene samples with high perfection of the atomic
      lattice are outstanding, but structural defects, which may appear during growth
      or processing, deteriorate the performance of graphene-based devices. However,
      deviations from perfection can be useful in some applications, as they make it
      possible to tailor the local properties of graphene and to achieve new
      functionalities. In this article, the present knowledge about point and line
      defects in graphene are reviewed. Particular emphasis is put on the unique
      ability of graphene to reconstruct its lattice around intrinsic defects, leading
      to interesting effects and potential applications. Extrinsic defects such as
      foreign atoms which are of equally high importance for designing graphene-based
      devices with dedicated properties are also discussed.

PMID- 21090761
TI  - Space-filling trialkoxysilane: synthesis and self-assembly into low-density
      monolayers.
AB  - A novel space-filling trialkoxysilane derivative was synthesized using a two-step
      strategy from commercially available starting materials to produce the precursor
      for the formation of low-density self-assembled monolayers. Self-assembled
      monolayers of the synthesized compound were prepared on three different
      substrates (Si/SiO(2), glass and ITO) and were characterized using contact angle,
      ellipsometry and sum-frequency generation spectroscopy. Removal of the space
      filling protecting group, (2-chlorophenyl)diphenyl methanol, yields a carboxy
      terminated surface. Correspondingly, the contact angle and film thickness
      decrease and the SFG spectra clearly indicate an increase in gauche defect
      concentration characteristic of a low-density disordered monolayer.

PMID- 21090763
TI  - Magnetic field induced assembly of highly ordered two-dimensional particle
      arrays.
AB  - Suspended magnetic beads are exposed to an external homogeneous magnetic field
      which rotates around the axis perpendicular to the field direction. Because of
      dipolar interactions, magnetic beads assemble in highly ordered two-dimensional
      hexagonal arrays perpendicular to the rotation axis. By continuous provision of
      the particle concentration, the growth modes of two-dimensional particle clusters
      and monolayers are observed. The structure of the resulting assembled objects is
      analyzed for different field frequencies and particle concentrations. We identify
      dynamic processes which enhance stability and reduce lattice distortions and,
      thus, allow for the application of these particle agglomerations as dynamic
      components in lab-on-a-chip technologies.

PMID- 21090762
TI  - Size and bandgap control in the solution-phase synthesis of near-infrared
      emitting germanium nanocrystals.
AB  - We present a novel colloidal synthesis of alkyl-terminated Ge nanocrystals based
      on the reduction of GeI(4)/GeI(2) mixtures. The size of the nanocrystals (2.3
      11.3 nm) was controlled by adjusting both the Ge(IV)/Ge(II) ratio and the
      temperature ramp rate following reductant injection. The near-infrared absorption
      (1.6-0.70 eV) and corresponding band-edge emission demonstrate the highly tunable
      quantum confinement effects in Ge nanocrystals prepared using this mixed-valence
      precursor method. A mechanism is proposed for the observed size control, which
      relies upon the difference in reduction temperatures for Ge(II) versus Ge(IV).

PMID- 21090764
TI  - Synthesis of pyridine-borane complexes via electrophilic aromatic borylation.
AB  - Pyridine-borane complexes were synthesized from 2-arylpyridines through an
      electrophilic aromatic borylation reaction with BBr(3). The intermediate 2-(2
      dibromoborylaryl)pyridines were stable enough to be handled in air and served as
      the synthetic platform for variously substituted pyridine-borane complexes. This
      facile method would be useful for the synthesis of aza-pi-conjugated materials
      having boron-nitrogen coordination.

PMID- 21090765
TI  - Prediction of collision-induced dissociation spectra of common N-glycopeptides
      for glycoform identification.
AB  - Confident identification of the glycan moieties in glycopeptides by collision
      induced dissociation (CID) requires accurate prediction of the CID spectrum of
      the glycopeptides. In this Article, the kinetic model for the prediction of
      peptide CID spectra is extended to predict the CID spectra of N-glycopeptides.
      The model was trained with 1831 ion-trap CID spectra of N-glycopeptides and is
      able to predict ion-trap CID spectra with excellent accuracy in ion intensities
      for N-glycopeptides up to 8000 u in mass. A total of 524 common glycoforms
      including complex N-glycans with 2-4 antennas, plus high-mannose type and hybrid
      type, can be predicted.

PMID- 21090766
TI  - All-(111) surface silicon nanowires: selective functionalization for biosensing
      applications.
AB  - We demonstrate the utilization of selective functionalization of carbon-silicon
      (C-Si) alkyl and alkenyl monolayers covalently linked to all-(111) surface
      silicon nanowire (Si-NW) biosensors. Terminal amine groups on the functional
      monolayer surfaces were used for conjugation of biotin n-hydroxysuccinimide
      ester. The selective functionalization is demonstrated by contact angle, X-ray
      photoelectron spectroscopy (XPS), and high-resolution scanning electron
      microscopy (HRSEM) of 5 nm diameter thiolated Au nanoparticles linked with
      streptavidin and conjugated to the biotinylated all-(111) surface Si-NWs.
      Electrical measurements of monolayer passivated Si-NWs show improved device
      behavior and performance. Furthermore, an analytical model is presented to
      demonstrate the improvement in detection sensitivity of the alkyl and alkenyl
      passivated all-(111) Si-NW biosensors compared to conventional nanowire biosensor
      geometries and silicon dioxide passivation layers as well as interface design and
      electrical biasing guidelines for depletion-mode sensors.

PMID- 21090767
TI  - Concentration and medium micellar kinetic effects caused by morphological
      transitions.
AB  - The reaction methyl naphthalene-2-sulfonate + Br(-) was investigated in several
      alkanediyl-alpha-omega-bis(dodecyldimethylammonium) bromide, 12-s-12,2Br(-) (with
      s = 2, 3, 4, 5, 6, 8, 10, 12), micellar solutions in the absence and in the
      presence of various additives. The additives were 1,2-propylene glycol, which
      remains in the bulk phase, N-decyl N-methylglucamide, MEGA10, which forms mixed
      micelles with the dimeric surfactants, and 1-butanol, which distributes between
      the aqueous and micellar phases. Information about the micellar reaction media
      was obtained by using conductivity and fluorescence measurements. In all cases,
      with the exception of water-1,2-prop 12-5-12,2Br(-) micellar solutions, with 30%
      weight percentage of the organic solvent, a sphere-to-rod transition takes place
      upon increasing surfactant concentration. In order to quantitatively explain the
      experimental data within the whole surfactant concentration range, a kinetic
      equation based on the pseudophase kinetic model was considered, together with the
      decrease in the micellar ionization degree accompanying micellar growth. However,
      theoretical predictions did not agree with the experimental kinetic data for
      surfactant concentrations above the morphological transition. An empirical
      kinetic equation was proposed in order to explain the data. It contains a
      parameter b which is assumed to account for the medium micellar kinetic effects
      caused by the morphological transition. The use of this empirical equation
      permits the quantitative rationalization of the kinetic micellar effects in the
      whole surfactant concentration range.

PMID- 21090768
TI  - Pentacene films on Cu(119).
AB  - The molecular structure of thin pentacene film grown on a Cu(119) surface has
      been studied by near-edge X-ray absorption fine structure spectroscopy and
      scanning tunneling microscopy. The interaction between the pi-molecular orbitals
      delocalized on the aromatic rings and the underlying copper substrate was deduced
      from XAS spectra. Pentacene molecules arrange with the main axis almost parallel
      with the Cu terraces according to the measured polarization dependence of the C
      1s absorption spectra. For thickness exceeding 4 nm an upright arrangement of the
      molecules was observed with a dense herringbone-like ordering. The present study
      thus demonstrates that highly ordered pentacene films can be obtained on a
      Cu(119) vicinal surface both in a flat orientation for low coverages and in a
      bulk-like herringbone orientation for higher coverages.

PMID- 21090769
TI  - Non-centrosymmetric tetrameric assemblies of tetramethylammonium halides with
      uranyl salophen complexes in the solid state.
AB  - Ditopic salophen-UO(2) receptors 1-4 and 7 co-crystallize with
      tetramethylammonium (TMA) chloride and fluoride salts producing good quality
      crystals amenable for X-ray diffraction characterization. The arrangement of the
      receptor and salt units in the crystal lattice is such that tetrameric ball
      shaped assemblies are formed, where an inner cluster of four TMA cations are
      surrounded by an outer shell of four UO(2)-bound anions. These elaborate
      architectures, which occur in all cases, regardless of a certain degree of
      structural modification on the receptors, lead to lattices that belong to non
      centrosymmetric (NCS) space groups. Interestingly, the tetragonal symmetry of the
      tetrameric ball-shaped assemblies is either retained (I4) or lost (R3c and I43d)
      at the lattice level, without compromising the NCS nature of the crystal
      lattices. The principal X-ray investigation on TMAX (X = Cl/F) co-crystals, that
      is, 1-(TMA)Cl, 2-(TMA)Cl, 3-(TMA)Cl, 4-(TMA)Cl, 7-(TMA)Cl, and 7-(TMA)F, is
      accompanied by NMR and electrospray ionization (ESI) mass spectrometry studies to
      gather additional insight on the modality of formation of the solid state
      structures observed. The important role of cation-pi interactions in the receptor
      salt recognition process is renewed and strengthened by comparison with NMR
      titration data with a novel reference compound, the salophen-UO(2) complex 8.
      Given the importance of NCS and polar crystalline solids in the development of
      functional materials, this study shows that this property can be introduced into
      elaborate host-guest systems, as those which assemble in the architectures
      described here, thus expanding its field of applicability.

PMID- 21090770
TI  - SWNT-MWNT hybrid filter attains high viral removal and bacterial inactivation.
AB  - We describe the concept and demonstrate the efficacy of a novel SWNT-MWNT hybrid
      filter for the removal and inactivation of microbial pathogens from water. The
      filter is composed of a thin SWNT layer (0.05 mg cm(-2)) on top of a thicker MWNT
      layer (0.27 mg cm(-2)) supported by a microporous support membrane. The SWNT-MWNT
      filter exhibits high log removal of several model viruses (MS2, PRD1, and T4
      bacteriophages) by depth filtration, which predominantly takes place in the
      thicker and more uniform MWNT layer. The filter removes all bacteria by a sieving
      mechanism, with the top SWNT layer providing high levels of inactivation of model
      bacteria (Escherichia coli K12 and Staphylococcus epidermidis), as well as
      microbes from river water and treated wastewater effluent. The dual-layer SWNT
      MWNT filter lays the framework for new possibilities in point-of-use water
      filtration.

PMID- 21090772
TI  - 6-Membered pseudocyclic IBX acids: syntheses, X-ray structural characterizations,
      and oxidation reactivities in common organic solvents.
AB  - We designed and synthesized lambda(5)-cyclic periodinanes 1 and 2, which are
      homologous to IBX (1-hydroxy-1-oxo-1H-1lambda(5)-benzo[d][1,2]iodoxol-3-one) by
      one carbon, to thwart close packing of molecules in the crystal lattice to permit
      solubility in common organic solvents and to facilitate oxidations with enhanced
      reactivity. The X-ray crystal structures revealed that both 1 and 2 exist in the
      solid state as pseudocyclic (PC) acids, i.e., 1PC and 2PC, and that the molecules
      in the lattice are less weakly associated as compared to those in the parent IBX
      due to the twisting introduced via the sp(3) benzylic carbon. Both 1PC and 2PC
      are found to dissolve in palpable amounts in DCM and acetonitrile to allow
      oxidation of a variety of alcohols and sulfides to carbonyl compounds and
      sulfoxides in a facile manner. The subtle differences in the sterics due to
      methyl and ethyl substituents in 1PC and 2PC are found to manifest in contrasting
      reactivities in that the oxidations of alcohols occur faster with 2PC, while
      those of sulfides to sulfoxides occur more rapidly with 1PC.

PMID- 21090771
TI  - Characterization of the effect of NaCl and trehalose on the thermotropic
      hysteresis of DOPC lipids during freeze/thaw.
AB  - This study characterizes the freeze/thaw behavior of large unilamellar DOPC
      vesicles in the presence of 0.5 or 4 M NaCl and 73 to 146 mM trehalose using
      Fourier transform infrared (FTIR) spectroscopy. Differences in lipid hydration
      between cooling and heating caused hysteresis in lipid phase change behavior and
      altered post-thaw lipid chain order. Lipids transitioned to a more ordered state
      during cooling. However, with heating, there was further conversion to a more
      ordered state at temperatures lower than the chain melting temperature. This
      conversion was more pronounced at higher concentrations of NaCl due to the
      formation of NaCl dihydrate crystals and the resulting changes in lipid
      hydration. Trehalose was shown to be capable of abrogating the severe dehydration
      effect at sufficiently high trehalose/NaCl concentrations by suppressing the
      formation of the NaCl dihydrate crystals. Moreover, trehalose enhanced recovery
      of prefreeze membrane structure.

PMID- 21090773
TI  - Syntheses and crystal structures of a series of alkaline earth vanadium selenites
      and tellurites.
AB  - Six new novel alkaline-earth metal vanadium(V) or vanadium(IV) selenites and
      tellurites, namely, Sr(2)(VO)(3)(SeO(3))(5), Sr(V(2)O(5))(TeO(3)),
      Sr(2)(V(2)O(5))(2)(TeO(3))(2)(H(2)O), Ba(3)(VO(2))(2)(SeO(3))(4),
      Ba(2)(VO(3))Te(4)O(9)(OH), and Ba(2)V(2)O(5)(Te(2)O(6)), have been prepared and
      structurally characterized by single crystal X-ray diffraction analyses. These
      compounds exhibit six different anionic structures ranging from zero-dimensional
      (0D) cluster to three-dimensional (3D) network. Sr(2)(VO)(3)(SeO(3))(5) features
      a 3D anionic framework composed of VO(6) octahedra that are bridged by SeO(3)
      polyhedra. The oxidation state of the vanadium cation is +4 because of the
      partial reduction of V(2)O(5) by SeO(2) at high temperature.
      Ba(3)(VO(2))(2)(SeO(3))(4) features a 0D [(VO(2))(SeO(3))(2)](3-) anion.
      Sr(V(2)O(5))(TeO(3)) displays a unique 1D vanadium(V) tellurite chain composed of
      V(2)O(8) and V(2)O(7) units connected by tellurite groups, forming 4- and 10-MRs,
      whereas Sr(2)(V(2)O(5))(2)(TeO(3))(2)(H(2)O) exhibits a 2D layer consisting of
      [V(4)O(14)] tetramers interconnected by bridging TeO(3)(2-) anions with the
      Sr(2+) and water molecules located at the interlayer space.
      Ba(2)(VO(3))Te(4)O(9)(OH) exhibits a one-dimensional (1D) vanadium tellurite
      chain composed of a novel 1D [Te(4)O(9)(OH)](3-) chain further decorated by VO(4)
      tetrahedra. Ba(2)V(2)O(5)(Te(2)O(6)) also features a 1D vanadium(V) tellurites
      chain in which neighboring VO(4) tetrahedra are bridged by [Te(2)O(6)](4-)
      dimers. The existence of V(4+) ions in Sr(2)(VO)(3)(SeO(3))(5) is also confirmed
      by magnetic measurements. The results of optical diffuse-reflectance spectrum
      measurements and electronic structure calculations based on density functional
      theory (DFT) methods indicate that all six compounds are wide-band gap
      semiconductors.

PMID- 21090774
TI  - n-Type field effect transistors based on rigid rod and liquid crystalline
      alternating copoly(benzobisoxazole) imides containing perylene and/or
      naphthalene.
AB  - The synthesis, characterization, and device studies of poly(benzobisoxazole
      imide)s containing perylene or naphthalene units in an alternating fashion with
      the oxazole unit are described. Photoinduced energy transfer and charge
      separation were studied in methanesulfonic acid (MSA) solution via absorption,
      excitation, and steady-state fluorescence studies. Excitation of the bisoxazole
      moiety resulted in enhanced emission from the perylene bisimide unit as a result
      of FRET (Forster resonance energy transfer). The influence of the imide
      substitution into the linear chain of poly(benzobisoxazole) (PBO) on its solid
      state packing was examined by wide-angle X-ray diffraction (WXRD) analysis.
      Bottom contact field effect transistors (FET) based on thermally annealed polymer
      films were fabricated and studied. The polymers showed n-type charge transport
      and current modulation with an on/off ratio greater than 10(2). It was observed
      that the FETs consisting of the random copolymer of bisoxazole containing both
      perylene as well as naphthalene bisimide units had higher performance parameters
      such as better mobility (MU(e)) and I(on)/I(off) ratio compared to those of the
      pristine systems.

PMID- 21090775
TI  - Three-dimensional assembly of nanoparticles from charged aerosols.
AB  - The capability of assembling nanoparticles into a desired ordered pattern is a
      key to realize novel devices which are based not only on the unique properties of
      nanoparticles but also on the arrangements of nanoparticles. While two
      dimensional arrays of nanoparticles have been successfully demonstrated by
      various techniques, a controlled way of building ordered arrays of three
      dimensional (3D) nanoparticle structures remains challenging. We report that a
      variety of 3D nanoparticle structures can be formed in a controlled way based on
      the ion-induced focusing, electrical scaffold, and antenna effects from charged
      aerosols. Particle trajectory calculations successfully predict the whole process
      of 3D assembly. New surface enhanced Raman scattering substrates based on our 3D
      assembly were constructed as an example showing the viability of the present
      approach. This report extends the current capability of positioning nanoparticles
      on surface to another spatial dimension, which can serve as the foundation of
      future optical, magnetic, and electronic devices taking the advantage of
      multidimensions.

PMID- 21090776
TI  - Facile domino access to chiral mono-, bi-, and tricyclic 2,3-dihydrofurans.
AB  - The asymmetric domino Michael-S(N)2 reaction of various 1,3-dicarbonyl compounds
      to alpha-bromonitroalkenes is described for the first time, employing readily
      available cinchona-derived bifunctional thioureas as organocatalysts. The novel
      transformations were highly regio-, chemo-, diastereo-, and enantioselective,
      which simultaneously gave the chiral tricyclic 2,3-dihydrofurans, bicyclic 2,3
      dihydrofurans, and tetrasubstituted 2,3-dihydrofurans with two vicinal chiral
      carbon centers.

PMID- 21090778
TI  - Electrochemical tuning of the optoelectronic properties of a fluorene-based
      conjugated polymer.
AB  - The electrochemical reduction of a fluorene-based conjugated polymer, poly(9
      fluorenone-alt-9,9-dioctylfluorene), was investigated for the first time. The
      carbonyl group in the fluorenone unit was selectively and quantitatively
      converted to the methylene group, as determined by (1)H NMR, IR, and energy
      dispersive X-ray (EDX) analysis. The optical and electrochemical properties of
      the polymers were studied by UV-vis, photoluminescence (PL), and cyclic
      voltammetry (CV) measurements and were found to be tunable by varying the
      reduction level.

PMID- 21090777
TI  - Reversible cobalt ion binding to imidazole-modified nanopipettes.
AB  - In this report, we demonstrate that quartz nanopipettes modified with an
      imidazole-terminated silane respond to metal ions (Co(2+)) in solution. The
      response of nanopipettes is evaluated through examination of the ion current
      rectification ratio. When nanopipettes are cycled between solutions of different
      pH, adsorbed Co(2+) can be released from the nanopipette surface, to regenerate
      binding sites of the nanopipette. These results demonstrate that rectification
      based sensing strategies for nanopore sensors can benefit from selection of
      recognition elements with intermediate binding affinities, such that reversible
      responses can be attained.

PMID- 21090779
TI  - Binary mixture of nonadditive hard spheres adsorbed in a slit pore: a study of
      the population inversion by the integral equations theory.
AB  - The structure of a binary mixture of nonadditive hard spheres confined in a slit
      pore is studied by the integral equations method in which the confining medium
      acts as a giant particle at infinite dilution. The adsorption/desorption curves
      are studied as a function of the composition and density, when the homogeneous
      bulk mixture is near the demixing instability. The Ornstein-Zernike integral
      equations are solved with the reference functional approximation closure in which
      the bridge functions are derived from Rosenfeld's hard sphere functional for
      additive hard sphere. To study the high composition asymmetry regime in which a
      population inversion occurs, we developed an approximate closure that overcomes
      the no solution problem of the integral equation. By comparison with simulation
      data, this method is shown to be sufficiently accurate for predicting the
      threshold density for the population inversion. The predictions of simpler
      closure relations are briefly examined.

PMID- 21090783
TI  - Templating alpha-helical poly(L-lysine)/polyanion complexes by nanostructured
      uniaxially oriented ultrathin polyethylene films.
AB  - We report a templating effect of uniaxially oriented melt-drawn polyethylene (MD
      PE) films on alpha-helical poly(L-lysine)/poly(styrenesulfonate) (alpha-PLL/PSS)
      complexes deposited by the layer-by-layer (LBL) method. The melt-drawing process
      induced an MD-PE fiber texture consisting of nanoscale lamellar crystals embedded
      in amorphous regions on the MD-PE film surface whereby the common
      crystallographic c axis is the PE molecular chain direction parallel to the
      uniaxial melt-drawing direction. The MD-PE film and the alpha-PLL/PSS deposit
      were analyzed by atomic force microscopy (AFM) and in situ attenuated total
      reflection Fourier transform infrared spectroscopy (ATR-FTIR) using polarized
      light as a complementary method. Both methods revealed that alpha-PLL/PSS
      complexes adsorbed at the MD-PE surface were anisotropic and preferentially
      oriented perpendicular to the crystallographic c direction of the MD-PE film.
      Quantitatively, from AFM image analysis and ATR-FTIR dichroism of the amide II
      band of the alpha-PLL, mean cone opening angles of 12-18 degrees  for both
      rodlike alpha-PLL and the anisotropic alpha-PLL/PSS complexes with respect to the
      PE lamellae width direction were obtained. A model for the preferred alignment of
      alpha-PLL along the protruding PE lamellae is discussed, which is based on
      possible hydrophobic driving forces for the minimization of surface free energy
      at molecular and supermolecular topographic steps of the PE surface followed by
      electrostatic interactions between the interconnecting PSS and the alpha-PLL
      during layer-by-layer adsorption. This study elucidates the requirements and
      mechanisms involved in orienting biomolecules and may open up a path for
      designing templates to induce directed protein adsorption and cell growth by
      oriented polypeptide- or protein-modified PE surfaces.

PMID- 21090780
TI  - Base flipping free energy profiles for damaged and undamaged DNA.
AB  - Lesion-induced thermodynamic destabilization is believed to facilitate beta
      hairpin intrusion by the human XPC/hHR23B nucleotide excision repair (NER)
      recognition factor, accompanied by partner-base flipping, as suggested by the
      crystal structure of the yeast orthologue (Min, J. H., and Pavletich, N. P.
      (2007) Nature 449, 570-575). To investigate this proposed mechanism, we employed
      the umbrella sampling method to compute partner base flipping free energies for
      the repair susceptible 14R (+)-trans-anti-DB[a,l]P-N(2)-dG modified duplex 11
      mer, derived from the fjord region polycyclic aromatic hydrocarbon
      dibenzo[a,l]pyrene, and for the undamaged duplex. Our flipping free energy
      profiles show that the adduct has a lower flipping barrier by ~7.7 kcal/mol,
      consistent with its thermally destabilizing impact on the damaged DNA duplex and
      its susceptibility to NER.

PMID- 21090781
TI  - Three-dimensional scaffolds for tissue engineering: the importance of uniformity
      in pore size and structure.
AB  - To validate the importance of uniformity in pore size and structure of a scaffold
      for tissue engineering, we fabricated two types of scaffolds with uniform
      (inverse opal scaffolds) and nonuniform pore sizes and structures, and then
      evaluated their properties in terms of diffusion of macromolecules, spatial
      distribution of fibroblasts, and differentiation of preosteoblasts. Our results
      confirmed the superior performance of the inverse opal scaffolds due to the
      uniform pore size, homogeneous environment, and high interconnectivity: a higher
      diffusion rate, a uniform distribution of cells, and a higher degree of
      differentiation. In addition, we found that both the differentiation of cells and
      secretion of extracellular matrix were dependent on the properties of the
      individual pore to which the cells were attached, rather than the bulk properties
      of a scaffold. Our results clearly indicate that inverse opal scaffolds could
      provide a better microenvironment for cells in comparison to a scaffold with
      nonuniform size and structure.

PMID- 21090784
TI  - Three-dimensional structures of OSW-1 and its congener.
AB  - The 3D structures of an antitumor glycosylsterol OSW-1 and its closely related
      congener were investigated by NMR studies and an X-ray crystallographic analysis.
      The disaccharide moiety was found as a structural scaffold for the formation of a
      hydrophobic cluster by the biologically required functionalities.

PMID- 21090785
TI  - Zr doping on one-dimensional titania nanomaterials synthesized in supercritical
      carbon dioxide.
AB  - The growth mechanism of one-dimensional metal oxide nanotubular structures is of
      tremendous current interest to tailor materials using "green" synthetic
      procedures for emerging industries in alternative energy and biomaterials. In
      this study, ZrO(2)-modified TiO(2) nanorods and tubular structures were
      successfully synthesized via a surfactant-free sol-gel route using supercritical
      carbon dioxide (scCO(2)) as the solvent/drying agent. The effect of metal
      alkoxide concentration (0.35-1.4 mol/L), acid/metal alkoxide ratio (R = 3-7), and
      Zr ratio (0-20%) was examined on the morphology and crystallinity of the
      resulting nanostructures as measured by electron microscopy (SEM and TEM), EDX,
      XPS, and XRD. The electron microscopy results showed that the crystal growth of
      the synthesized binary Ti-Zr nanomaterials could be tailored by changing the
      operating variables with nanotubular structure formed at metal alkoxide
      concentration of 1.2 mol/L, R = 5-6, and Zr ratio between 4% and 20%. Gelation
      kinetics for this new system was also studied and revealed that increasing
      alkoxide concentration and R value enhanced the gelation kinetics. In situ and
      powder FTIR results revealed that this Ti-Zr binary system follows a similar
      reaction scheme to that of either single-component system, showing the
      flexibility of this approach for tailoring nanotubular production.

PMID- 21090786
TI  - Dynamics of highly excited nitroaromatics.
AB  - Although the photodissociation of nitroaromatics in low excitation electronic
      states has been extensively studied in recent decades, little is known about the
      highly excited electronic states. The fragmentation dynamics of three
      nitroaromatics, nitrobenzene, o-nitrotoluene, and m-nitrotoluene, in highly
      excited states, populated by the absorption of two photons at 271 nm, are studied
      with time-of-flight mass spectrometry. The temporal evolutions of the highly
      excited states are monitored by one-photon ionization at 408 nm. The transients
      of parent and fragment ions exhibit two ultrafast deactivation processes. The
      first process is ultrafast internal conversion from the initial excitation to
      Rydberg states in tens of femtoseconds. The second one is conversion from the
      Rydberg states to the vibrational manifold in the ground electronic states within
      hundreds of femtoseconds. The internal conversion process is accelerated by
      methyl substitution. In o-nitrotoluene, the two processes become much faster due
      to the hydrogen transfer from the CH(3) to the NO(2) group (ortho effect).

PMID- 21090787
TI  - Modulating the light switch by (3)MLCT-(3)pipi* state interconversion.
AB  - The spectroscopic, electronic, and DNA-binding characteristics of two novel
      ruthenium complexes based on the dialkynyl ligands 2,3-bis(phenylethynyl)-1,4,8,9
      tetraaza-triphenylene (bptt, 1) and 2,3-bis(4-tert-butyl-phenylethynyl)-1,4,8,9
      tetraaza-triphenylene (tbptt, 2) have been investigated. Electronic structure
      calculations of bptt reveal that the frontier molecular orbitals are localized on
      the pyrazine-dialkynyl portion of the free ligand, a property that is reflected
      in a red shift of the lowest energy electronic transition (1: lambda(max) = 393
      nm) upon substitution at the terminal phenyl groups (2: lambda(max) = 398 nm).
      Upon coordination to ruthenium, the low-energy ligand-centered transitions of 1
      and 2 are retained, and metal-to-ligand charge transfer transitions (MLCT)
      centered at lambda(max) = 450 nm are observed for [Ru(phen)(2)bptt](2+)(3) and
      [Ru(phen)(2)tbptt](2+)(4). The photophysical characteristics of 3 and 4 in
      ethanol closely parallel those observed for [Ru(bpy)(3)](2+) and
      [Ru(phen)(3)](2+), indicating that the MLCT excited state is primarily localized
      within the [Ru(phen)(3)](2+) manifold of 3 and 4, and is only sparingly affected
      by the extended conjugation of the bptt framework. In an aqueous environment, 3
      and 4 possess notably small luminescence quantum yields (3: phi(H(2)O) = 0.005,
      4: phi(H(2)O) = 0.011) and biexponential decay kinetics (3: tau(1) = 40 ns,
      tau(2) = 230 ns; 4: tau(1) ~ 26 ns, tau(2) = 150 ns). Addition of CT-DNA to an
      aqueous solution of 3 causes a significant increase in the luminescence quantum
      yield (phi(DNA) = 0.045), while the quantum yield of 4 is relatively unaffected
      (phi(DNA) = 0.013). The differential behavior demonstrates that tert-butyl
      substitution on the terminal phenyl groups inhibits the ability of 4 to
      intercalate with DNA. Such changes in intrinsic luminescence demonstrate that 3
      binds to DNA via intercalation (K(b) = 3.3 * 10(4) M(-1)). The origin of this
      light switch behavior involves two competing (3)MLCT states similar to that of
      the extensively studied light switch molecule [Ru(phen)(2)dppz](2+). The solvent-
      and temperature-dependence of the luminescence of 3 reveal that the extended
      ligand aromaticity lowers the energy of the (3)pipi* excited state into
      competition with the emitting (3)MLCT state. Interconversion between these two
      states plays a significant role in the observed photophysics and is responsible
      for the dual emission in aqueous environments.

PMID- 21090788
TI  - Indium-catalyzed homo-Nazarov cyclizations of alkenyl cyclopropyl ketones.
AB  - Herein, an efficient Lewis acid catalyzed protocol for the homo-Nazarov
      cyclizations of alkenyl cyclopropyl ketones is reported. Alkenes bearing beta
      hydrogens (or silyl groups) provide 1.5:1 mixtures of methylene cyclohexenols and
      cyclohexenones. When no beta-hydrogens (or silyl groups) are present, only
      cyclohexenones are observed. Products are rapidly formed in good to high yields
      (up to 93%) under mild conditions and could be readily derivatized.

PMID- 21090789
TI  - Graphene oxide-periodic mesoporous silica sandwich nanocomposites with vertically
      oriented channels.
AB  - This paper describes the synthesis and characterization of single-layer graphene
      oxide-periodic mesoporous silica sandwich nanocomposites. Through a comprehensive
      exploration of the synthesis conditions, it has proven possible to create the
      first example of a graphene oxide-periodic mesoporous silica nanocomposite in
      which hexagonal symmetry PMS film grows on both sides of the graphene oxide
      sheets with the mesoporous channels vertically aligned with respect to the
      graphene oxide surface. The formation of this novel architecture is found to be
      very sensitive to pH, the ratio of surfactant template to graphene oxide, the
      amount of silica precursor, and the temperature of the synthesis. On the basis of
      the collected data of a multi-technique analysis, it is proposed that the mode of
      formation of the nanocomposite involves the co-assembly of silicate-surfactant
      admicelles on opposite sides of graphene oxide platelets acting thereby as a
      template for growth of vertical mesopores off the platelet surface. These
      composites showed semiconductive behavior with electrical conductivity
      sensitively responding to analyte vapor exposure. The discovery of graphene oxide
      periodic mesoporous silica sandwich nanocomposites will provide new opportunities
      for research that exploits the synergism of the graphene oxide and periodic
      mesoporous silica parts.

PMID- 21090790
TI  - Thermally induced alkylation of diamond.
AB  - We present an approach for the thermally activated formation of alkene-derived
      self-assembled monolayers on oxygen-terminated single and polycrystalline diamond
      surfaces. Chemical modification of the oxygen and hydrogen plasma-treated samples
      was achieved by heating in 1-octadecene. The resulting layers were characterized
      using X-ray photoelectron spectroscopy, thermal desorption spectroscopy, atomic
      force microscopy, Fourier transform infrared spectroscopy, and water contact
      angle measurements. This investigation reveals that alkenes selectively attach to
      the oxygen-terminated sites via covalent C-O-C bonds. The hydrophilic oxygen
      terminated diamond is rendered strongly hydrophobic following this reaction. The
      nature of the process limits the organic layer growth to a single monolayer, and
      FTIR measurements reveal that such monolayers are dense and well ordered. In
      contrast, hydrogen-terminated diamond sites remain unaffected by this process.
      This method is thus complementary to the UV-initiated reaction of alkenes with
      diamond, which exhibits the opposite reactivity contrast. Thermal alkylation
      increases the range of available diamond functionalization strategies and
      provides a means of straightforwardly forming single organic layers in order to
      engineer the surface properties of diamond.

PMID- 21090791
TI  - A rewired green fluorescent protein: folding and function in a nonsequential,
      noncircular GFP permutant.
AB  - The sequential order of secondary structural elements in proteins affects the
      folding and activity to an unknown extent. To test the dependence on sequential
      connectivity, we reconnected secondary structural elements by their solvent
      exposed ends, permuting their sequential order, called "rewiring". This new
      protein design strategy changes the topology of the backbone without changing the
      core side chain packing arrangement. While circular and noncircular permutations
      have been observed in protein structures that are not related by sequence
      homology, to date no one has attempted to rationally design and construct a
      protein with a sequence that is noncircularly permuted while conserving three
      dimensional structure. Herein, we show that green fluorescent protein can be
      rewired, still functionally fold, and exhibit wild-type fluorescence excitation
      and emission spectra.

PMID- 21090792
TI  - Calculations of the free energy of interaction of the c-Fos-c-Jun coiled coil:
      effects of the solvation model and the inclusion of polarization effects.
AB  - The leucine zipper region of activator protein-1 (AP-1) comprises the c-Jun and c
      Fos proteins and constitutes a well-known coiled coil protein-protein interaction
      motif. We have used molecular dynamics (MD) simulations in conjunction with the
      molecular mechanics/Poisson-Boltzmann generalized-Born surface area [MM/PB(GB)SA]
      methods to predict the free energy of interaction of these proteins. In
      particular, the influence of the choice of solvation model, protein force field,
      and water potential on the stability and dynamic properties of the c-Fos-c-Jun
      complex were investigated. Use of the AMBER polarizable force field ff02 in
      combination with the polarizable POL3 water potential was found to result in
      increased stability of the c-Fos-c-Jun complex. MM/PB(GB)SA calculations revealed
      that MD simulations using the POL3 water potential give the lowest predicted free
      energies of interaction compared to other nonpolarizable water potentials. In
      addition, the calculated absolute free energy of binding was predicted to be
      closest to the experimental value using the MM/GBSA method with independent MD
      simulation trajectories using the POL3 water potential and the polarizable ff02
      force field, while all other binding affinities were overestimated.

PMID- 21090793
TI  - Exciton dynamics in semiconducting carbon nanotubes.
AB  - We report a femtosecond transient absorption spectroscopic study on the (6, 5)
      single-walled carbon nanotubes and the (7, 5) inner tubes of a dominant double
      walled carbon nanotube species. We found that the dynamics of exciton relaxation
      probed at the first transition-allowed state (E(11)) of a given tube type
      exhibits a markedly slower decay when the second transition-allowed state (E(22))
      is excited than that measured by exciting its first transition-allowed state
      (E(11)). A linear intensity dependence of the maximal amplitude of the transient
      absorption signal is found for the E(22) excitation, whereas the corresponding
      amplitude scales linearly with the square root of the E(11) excitation intensity.
      Theoretical modeling of these experimental findings was performed by developing a
      continuum model and a stochastic model with explicit consideration of the
      annihilation of coherent excitons. Our detailed numerical simulations show that
      both models can reproduce reasonably well the initial portion of decay kinetics
      measured upon the E(22) and E(11) excitation of the chosen tube species, but the
      stochastic model gives qualitatively better agreement with the intensity
      dependence observed experimentally than those obtained with the continuum model.

PMID- 21090794
TI  - New insights into applicability of electron-counting rules in transition metal
      encapsulating Ge cage clusters.
AB  - The relative stability of Sc, Ti, and V encapsulating Ge(n) clusters in the size
      range n = 14-20 has been studied through first-principles electronic structure
      calculations based on density functional theory. Variations of the embedding
      energy, gap between the highest occupied and the lowest occupied molecular
      orbitals, ionization potential, vertical detachment energy, and electron affinity
      with cluster size have been calculated to identify clusters with enhanced
      stability. The enhanced stability of some clusters can be very well explained as
      due to the formation of a filled shell free-electron gas inside the Ge cages. For
      the first time, direct evidence of the formation of a free-electron gas is also
      presented. In some other clusters, enhanced stability is found to originate from
      geometric effects. Some clusters that may be expected to have enhanced stability
      from simple electron counting rules do not show that. These results provide new
      insights into the long-standing question of whether electron counting rules can
      explain the relative stability of transition metal encapsulated semiconductor
      clusters and show that these clusters are too complex for such simple
      generalizations.

PMID- 21090795
TI  - Lanthanide sensitization in II-VI semiconductor materials: a case study with
      terbium(III) and europium(III) in zinc sulfide nanoparticles.
AB  - This work explores the sensitization of luminescent lanthanide Tb(3+) and Eu(3+)
      cations by the electronic structure of zinc sulfide (ZnS) semiconductor
      nanoparticles. Excitation spectra collected while monitoring the lanthanide
      emission bands reveal that the ZnS nanoparticles act as an antenna for the
      sensitization of Tb(3+) and Eu(3+). The mechanism of lanthanide ion luminescence
      sensitization is rationalized in terms of an energy and charge transfer between
      trap sites and is based on a semiempirical model, proposed by Dorenbos and co
      workers (Dorenbos, P. J. Phys.: Condens. Matter 2003, 15, 8417-8434; J. Lumin.
      2004, 108, 301-305; J. Lumin. 2005, 111, 89-104. Dorenbos, P.; van der Kolk, E.
      Appl. Phys. Lett. 2006, 89, 061122-1-061122-3; Opt. Mater. 2008, 30, 1052-1057.
      Dorenbos, P. J. Alloys Compd. 2009, 488, 568-573; references 1-6.) to describe
      the energy level scheme. This model implies that the mechanisms of luminescence
      sensitization of Tb(3+) and Eu(3+) in ZnS nanoparticles are different; namely,
      Tb(3+) acts as a hole trap, whereas Eu(3+) acts as an electron trap. Further
      testing of this model is made by extending the studies from ZnS nanoparticles to
      other II-VI semiconductor materials; namely, CdSe, CdS, and ZnSe.

PMID- 21090796
TI  - beta-carboline alkaloids from Stellaria dichotoma var. lanceolata and their anti
      inflammatory activity.
AB  - The present investigation on the chemical constituents of the roots of Stellaria
      dichotoma var. lanceolata has resulted in the isolation of 21 beta-carboline
      alkaloids, including 13 new compounds, dichotomides III-XIV (1-12) and
      dichotomine E (13), and eight known compounds. The structures of the new
      compounds were established on the basis of spectroscopic data analysis. Among
      these isolated alkaloids, five compounds were examined for their anti
      inflammatory potential for the inhibition of NO production in LPS-treated RAW
      264.7 cells. All compounds tested exhibited significant inhibition of NO
      production, with IC(50) values in the range of 11.3 to 19.3 MUM.

PMID- 21090797
TI  - Nonequilibrium phenomena in charge recombination of excited donor-acceptor
      complexes and free energy gap law.
AB  - The charge recombination dynamics of excited donor-acceptor complexes in polar
      solvents has been investigated within the framework of the stochastic approach.
      The model involves the excited state formation by the pump pulse and accounts for
      the reorganization of a number of intramolecular high-frequency vibrational
      modes, for their relaxation as well as for the solvent reorganization following
      nonexponential relaxation. The hot transitions accelerate the charge
      recombination in the low exergonic region and suppress it in the region of
      moderate exothermicity. This straightens the dependence of the logarithm of the
      charge recombination rate constant on the free energy gap to the form that can be
      fitted to the experimental data. The free energy dependence of the charge
      recombination rate constant can be well fitted to the multichannel stochastic
      model if the donor-acceptor complexes are separated into a few groups with
      different values of the electronic coupling. The model provides correct
      description of the nonexponential charge recombination dynamics in excited donor
      acceptor complexes, in particular, nearly exponential recombination in perylene
      tetracyanoethylene complex in acetonitrile. It appears that majority of the
      initially excited donor-acceptor complexes recombines in a nonthermal (hot) stage
      when the nonequilibrium wave packet passes through a number of term crossings
      corresponding to transitions toward vibrational excited states of the electronic
      ground state in the area of the low and moderate exothermicity.

PMID- 21090798
TI  - Catalytic asymmetric domino Michael addition-alkylation reaction:
      enantioselective synthesis of dihydrofurans.
AB  - A catalytic enantioselective synthesis of dihydrofurans has been developed. 1,3
      Dicarbonyl derivatives react with (E)-beta,beta-bromonitrostyrenes in the
      presence of a chiral bifunctional thiourea catalyst providing mild and efficient
      access to diverse polysubstituted dihydrofurans in good yields and
      enantioselectivities.

PMID- 21090799
TI  - Computational insights into the mechanism of porphobilinogen synthase.
AB  - Porphobilinogen synthase (PBGS) is a key enzyme in heme biosynthesis that
      catalyzes the formation of porphobilinogen (PBG) from two 5-aminolevulinic acid
      (5-ALA) molecules via formation of intersubstrate C-N and C-C bonds. The active
      site consists of several invariant residues, including two lysyl residues (Lys210
      and Lys263; yeast numbering) that bind the two substrate moieties as Schiff
      bases. Based on experimental studies, various reaction mechanisms have been
      proposed for this enzyme that generally can be classified according to whether
      the intersubstrate C-C or C-N bond is formed first. However, the detailed
      catalytic mechanism of PBGS remains unclear. In the present study, we have
      employed density functional theory methods in combination with chemical models of
      the two key lysyl residues and two substrate moieties in order to investigate
      various proposed reaction steps and gain insight into the mechanism of PBGS.
      Importantly, it is found that mechanisms in which the intersubstrate C-N bond is
      formed first have a rate-limiting barrier (17.5 kcal/mol) that is lower than
      those in which the intersubstrate C-C bond is formed first (22.8 kcal/mol).

PMID- 21090800
TI  - Pyridone and tetramic acid alkaloids from the spider pathogenic fungus
      Torrubiella sp. BCC 2165.
AB  - Torrubiellones A-D (1-4), new pyridone and tetramic acid alkaloids, were isolated
      from the spider pathogenic fungus Torrubiella sp. BCC 2165. Torrubiellone A (1)
      exhibited antimalarial activity with an IC(50) value of 8.1 MUM, while it showed
      very weak cytotoxic activity.

PMID- 21090801
TI  - Cytotoxic triterpenoids from Maytenus retusa.
AB  - Seven new triterpenoids (1-7) and 36 known compounds were isolated from the root
      bark of Maytenus retusa. Their structures were determined by 1D and 2D
      spectroscopic studies. Several compounds were evaluated for their cytotoxicity
      against the human tumor cell lines HL-60 and MCF-7. Some of them were cytotoxic,
      with IC(50) values ranging between 0.2 and 4.7 MUM.

PMID- 21090802
TI  - Unexpected C-Se cross-coupling reaction: copper oxide catalyzed synthesis of
      symmetrical diaryl selenides via cascade reaction of selenourea with aryl
      halides/boronic acids.
AB  - Selenourea is used as an effective selenium surrogate in the C-Se cross-coupling
      reaction catalyzed by copper oxide nanoparticles under ligand free conditions.
      This protocol has been utilized for the synthesis of a variety of symmetrical
      diaryl selenides in good to excellent yields from the readily available aryl
      halides/boronic acids.

PMID- 21090804
TI  - Synthesis of methyl N-Boc-(2S,4R)-4-methylpipecolate.
AB  - An efficient stereoselective synthesis of fully protected (2S,4R)-4
      methylpipecolic acid has been developed. The synthesis was achieved by initial
      asymmetric alpha-alkylation of glycine with a chiral iodide, affording the linear
      precursor as a single stereoisomer. Subsequent aldehyde formation using
      OsO(4)/NaIO(4) followed by immediate intramolecular cyclization afforded an
      enamine that was then subjected to hydrogenation to give the final compound in
      23% yield over 10 steps.

PMID- 21090803
TI  - Nitropyrrolins A-E, cytotoxic farnesyl-alpha-nitropyrroles from a marine-derived
      bacterium within the actinomycete family Streptomycetaceae.
AB  - Five new farnesyl-alpha-nitropyrroles, nitropyrrolins A-E (1-5), were isolated
      from the saline culture of the marine actinomycete strain CNQ-509. This strain
      belongs to the "MAR4" group of marine actinomycetes, which have been demonstrated
      to be a rich source of hybrid isoprenoid secondary metabolites. The structures of
      the nitropyrrolins are composed of alpha-nitropyrroles with functionalized
      farnesyl groups at the C-4 position. These compounds are the first examples of
      naturally occurring terpenyl-alpha-nitropyrroles. Chemical modifications,
      including one-step acetonide formation from an epoxide, and application of the
      modified Mosher method provided the full stereostructures and absolute
      configurations of these compounds. Several of the nitropyrrolins, nitropyrrolin D
      in particular, are cytotoxic toward HCT-116 human colon carcinoma cells, but show
      weak to little antibacterial activity against methicillin-resistant
      Staphylococcus aureus (MRSA).

PMID- 21090805
TI  - Ligand-induced formation of a transient tryptophan synthase complex with
      alphabetabeta subunit stoichiometry.
AB  - The prototypical tryptophan synthases form a stable heterotetrameric
      alphabetabetaalpha complex in which the constituting TrpA and TrpB1 subunits
      activate each other in a bidirectional manner. The hyperthermophilic archaeon
      Sulfolobus solfataricus does not contain a TrpB1 protein but instead two members
      of the phylogenetically distinct family of TrpB2 proteins, which are encoded
      within (sTrpB2i) and outside (sTrpB2a) the tryptophan operon. It has previously
      been shown that sTrpB2a does not functionally or structurally interact with
      sTrpA, whereas sTrpB2i substantially activates sTrpA in a unidirectional manner.
      However, in the absence of catalysis, no physical complex between sTrpB2i and
      sTrpA could be detected. In order to elucidate the structural requirements for
      complex formation, we have analyzed the interaction between sTrpA (alpha-monomer)
      and sTrpB2i (betabeta-dimer) by means of spectroscopy, analytical gel filtration,
      and analytical ultracentrifugation, as well as isothermal titration calorimetry.
      In the presence of the TrpA ligand glycerol 3-phosphate (GP) and the TrpB
      substrate l-serine, sTrpA and sTrpB2i formed a physical complex with a
      thermodynamic dissociation constant of about 1 MUM, indicating that the affinity
      between the alpha- and betabeta-subunits is weaker by at least 1 order of
      magnitude than the affinity between the corresponding subunits of prototypical
      tryptophan synthases. The observed stoichiometry of the complex was 1 subunit of
      sTrpA per 2 subunits of sTrpB2i, which corresponds to a alphabetabeta quaternary
      structure and testifies to a strong negative cooperativity for the binding of the
      alpha-monomers to the betabeta-dimer. The analysis of the interaction between
      sTrpB2i and sTrpA in the presence of several substrate, transition state, and
      product analogues suggests that the alphabetabeta complex remains stable during
      the whole catalytic cycle and disintegrates into alpha- and betabeta-subunits
      upon the release of the reaction product tryptophan. The formation of a transient
      tryptophan synthase complex, together with the observed low affinity of sTrpB2i
      for l-serine, couples the rate of tryptophan biosynthesis in S. solfataricus to
      the cytosolic availability of l-serine.

PMID- 21090806
TI  - Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization
      of human ABCC1.
AB  - Resistance to multiple anticancer agents is a major obstacle in the successful
      treatment of cancers. Overexpression of some ATP-binding cassette (ABC) membrane
      transporters such as ABCC1 has been shown to be a major contributor of multidrug
      resistance (MDR) in both laboratory cell line models and the clinical setting.
      ABCC1 has been thought to function as a homodimer with a putative dimerization
      domain located in the first 281 amino acid residues, including MSD0 and L0
      domains. In this study, we further mapped in detail the dimerization site and
      placed it in TM5 and ECL3 in MSD0 using co-expression and co-immunoprecipitation
      of a series of deletion constructs. TM5 and ECL3 in one subunit appear to
      interact with TM5 and ECL3 in the opposing subunit in a sequence-independent
      manner, but their physical location together with the hydrophobicity of TM5 and
      the length of ECL3 appears to be important contributors to the dimerization
      ability of ABCC1.

PMID- 21090808
TI  - Nonaqueous catalytic water oxidation.
AB  - The complex [Ru(Mebimpy)(bpy)(OH(2))](2+) [Mebimpy = 2,6-bis(1-methylbenzimidazol
      2-yl)pyridine; bpy = 2,2'-bipyridine] and its 4,4'-(PO(3)H(2)CH(2))(2)bpy
      derivative on oxide electrodes are water oxidation catalysts in propylene
      carbonate and 2,2,2-trifluoroethanol (TFE) to which water has been added as a
      limiting reagent. The rate of water oxidation is greatly enhanced relative to
      that with water as the solvent and occurs by a pathway that is first-order in
      H(2)O; an additional pathway that is first-order in acetate appears when TFE is
      used as the solvent.

PMID- 21090810
TI  - Organic reactions catalyzed by rhenium carbonyl complexes.

PMID- 21090809
TI  - Design, synthesis, and evaluation of dibenzo[c,h][1,6]naphthyridines as
      topoisomerase I inhibitors and potential anticancer agents.
AB  - Indenoisoquinoline topoisomerase I (Top1) inhibitors are a novel class of
      anticancer agents. Modifications of the indenoisoquinoline A, B, and D rings have
      been extensively studied in order to optimize Top1 inhibitory activity and
      cytotoxicity. To improve understanding of the forces that stabilize drug-Top1-DNA
      ternary complexes, the five-membered cyclopentadienone C-ring of the
      indenoisoquinoline system was replaced by six-membered nitrogen heterocyclic
      rings, resulting in dibenzo[c,h][1,6]naphthyridines that were synthesized by a
      novel route and tested for Top1 inhibition. This resulted in several compounds
      that have unique DNA cleavage site selectivities and potent antitumor activities
      in a number of cancer cell lines.

PMID- 21090811
TI  - The next decade of nanoscience and nanotechnology.

PMID- 21090813
TI  - Perspectives on the 2010 Nobel Prize in physics for graphene.
AB  - The 2010 Nobel Prize in physics was awarded to Andre Geim and Konstantin
      Novoselov for their groundbreaking experiments regarding the two-dimensional
      material graphene. Some personal perspectives about this award are presented.

PMID- 21090814
TI  - Discovery and characterization of non-ATP site inhibitors of the mitogen
      activated protein (MAP) kinases.
AB  - Inhibition of protein kinases has validated therapeutic utility for cancer, with
      at least seven kinase inhibitor drugs on the market. Protein kinase inhibition
      also has significant potential for a variety of other diseases, including
      diabetes, pain, cognition, and chronic inflammatory and immunologic diseases.
      However, as the vast majority of current approaches to kinase inhibition target
      the highly conserved ATP-binding site, the use of kinase inhibitors in treating
      nononcology diseases may require great selectivity for the target kinase. As
      protein kinases are signal transducers that are involved in binding to a variety
      of other proteins, targeting alternative, less conserved sites on the protein may
      provide an avenue for greater selectivity. Here we report an affinity-based, high
      throughput screening technique that allows nonbiased interrogation of small
      molecule libraries for binding to all exposed sites on a protein surface. This
      approach was used to screen both the c-Jun N-terminal protein kinase Jnk-1
      (involved in insulin signaling) and p38alpha (involved in the formation of
      TNFalpha and other cytokines). In addition to canonical ATP-site ligands,
      compounds were identified that bind to novel allosteric sites. The nature,
      biological relevance, and mode of binding of these ligands were extensively
      characterized using two-dimensional (1)H/(13)C NMR spectroscopy, protein X-ray
      crystallography, surface plasmon resonance, and direct enzymatic activity and
      activation cascade assays. Jnk-1 and p38alpha both belong to the MAP kinase
      family, and the allosteric ligands for both targets bind similarly on a ledge of
      the protein surface exposed by the MAP insertion present in the CMGC family of
      protein kinases and distant from the active site. Medicinal chemistry studies
      resulted in an improved Jnk-1 ligand able to increase adiponectin secretion in
      human adipocytes and increase insulin-induced protein kinase PKB phosphorylation
      in human hepatocytes, in similar fashion to Jnk-1 siRNA and to rosiglitazone
      treatment. Together, the data suggest that these new ligand series bind to a
      novel, allosteric, and physiologically relevant site and therefore represent a
      unique approach to identify kinase inhibitors.

PMID- 21090815
TI  - Characterization of an NADH-dependent persulfide reductase from Shewanella
      loihica PV-4: implications for the mechanism of sulfur respiration via FAD
      dependent enzymes.
AB  - The NADH-dependent persulfide reductase (Npsr), a recently discovered member of
      the PNDOR family of flavoproteins that contains both the canonical flavoprotein
      reductase domain and a rhodanese domain, is proposed to be involved in the
      dissimilatory reduction of S(0) for Shewanella loihica PV-4. We have previously
      shown that polysulfide is a substrate for this enzyme, and a recently determined
      structure of a closely related enzyme (CoADR-Rhod from Bacillus anthracis)
      suggested the importance of a bound coenzyme A in the mechanism. The work
      described here shows that the in vivo oxidizing substrates of Npsr are the
      persulfides of small thiols such as CoA and glutathione. C43S, C531S, and
      C43,531S mutants were created to determine the role of the flavoprotein domain
      cysteine (C43) and the rhodanese domain cysteine (C531) in the mechanism. The
      absolute requirement for C43 in persulfide or DTNB reductase activity shows that
      this residue is involved in S-S bond breakage. C531 contributes to, but is not
      required for, catalysis of DTNB reduction, while it is absolutely required for
      reduction of any persulfide substrates. Titrations of the enzyme with NADH,
      dithionite, titanium(III), or TCEP demonstrate the presence of a mixed-disulfide
      between C43 and a tightly bound CoA, and structures of the C43 and C43,531S
      mutants confirm that this coenzyme A remains tightly bound to the enzyme in the
      absence of a C43-CoA S-S bond. The structure of Npsr suggests a likely site for
      binding and reaction with the persulfide substrate on the rhodanese domain. On
      the basis of kinetic, titration, and structural data, a mechanism for the
      reduction of persulfides by Npsr is proposed.

PMID- 21090816
TI  - Torsional mechanics of DNA are regulated by small-molecule intercalation.
AB  - Whether the bend and twist mechanics of DNA molecules are coupled is unclear.
      Here, we report the direct measurement of the resistive torque of single DNA
      molecules to study the effect of ethidium bromide (EtBr) intercalation and
      pulling force on DNA twist mechanics. DNA molecules were overwound and unwound
      using recently developed magnetic tweezers where the molecular resistive torque
      was obtained from Brownian angular fluctuations. The effect of EtBr intercalation
      on the twist stiffness was found to be significantly different from the effect on
      the bend persistence length. The twist stiffness of DNA was dramatically reduced
      at low intercalator concentration (<10 nM); however, it did not decrease further
      when the intercalator concentration was increased by 3 orders of magnitude. We
      also determined the dependence of EtBr intercalation on the torque applied to
      DNA. We propose a model for the elasticity of DNA base pairs with intercalated
      EtBr molecules to explain the abrupt decrease of twist stiffness at low EtBr
      concentration. These results indicate that the bend and twist stiffnesses of DNA
      are independent and can be differently affected by small-molecule binding.

PMID- 21090817
TI  - A study of the vaporization enthalpies of some 1-substituted imidazoles and
      pyrazoles by correlation-gas chromatography.
AB  - The vaporization enthalpies of 1-methyl-, 1-ethyl-, 1-phenyl-, and 1
      benzylimidazole, 1-methyl- and 1-phenylpyrazole, and trans-azobenzene are
      evaluated by correlation-gas chromatography (C-GC) using a variety of azines and
      diazines as standards. The vaporization enthalpies obtained by C-GC when compared
      to literature values are approximately 14 kJ.mol(-1) smaller for the imidazoles
      and 6 kJ.mol(-1) smaller for the pyrazoles. The literature vaporization
      enthalpies of 1-methylpyrrole and 1-methylindole, two closely related compounds
      with one less nitrogen, are reproduced by C-GC. These results suggest that the
      magnitude of the intermolecular interactions present in 1-substituted imidazoles
      and pyrazoles are significantly larger than the those present in the reference
      compounds and greater than or equal in magnitude to the enhanced intermolecular
      interactions observed previously in aromatic 1,2-diazines. The vaporization
      enthalpy and vapor pressure of a trans-1,2-diazine, trans-azobenzene, measured by
      C-GC using similar standards reproduced the literature values within experimental
      error.

PMID- 21090818
TI  - Electron-nuclear and electron-electron double resonance spectroscopies show that
      the primary quinone acceptor QA in reaction centers from photosynthetic bacteria
      Rhodobacter sphaeroides remains in the same orientation upon light-induced
      reduction.
AB  - Reaction centers (RCs) from the photosynthetic bacterium Rhodobacter (Rb.)
      sphaeroides R-26 exhibit changes in the recombination kinetics of the charge
      separated radical-pair state, P(.+) Q(A)(.-), composed of the dimeric
      bacteriochlorophyll donor P and the ubiquinone-10 acceptor Q(A), depending on
      whether the RCs are cooled to cryogenic temperatures in the dark or under
      continuous illumination (Kleinfeld et al. Biochemistry 1984, 23, 5780-5786).
      Structural changes near redox-active cofactors have been postulated to be
      responsible for these changes in kinetics and to occur in the course of light
      induced oxidation and reduction of the cofactors thereby assuring a high quantum
      yield. Here we investigated such potential light-induced structural changes,
      associated with the formation of P(.+) Q(A)(.-), via pulsed electron-nuclear
      double resonance (ENDOR) at Q-band (34 GHz) and pulsed electron-electron double
      resonance (PELDOR) at W-band (95 GHz). Two types of light excitation have been
      employed for which identical RC samples were prepared: (a) one sample was frozen
      in the dark and then illuminated to generate transient P(.+) Q(A)(.-), and (b)
      one was frozen under illumination which resulted in both trapped and transient
      P(.+) Q(A)(.-) at 80 K. The hyperfine interactions between Q(A)(.-) and the
      protein were found to be the same in RCs frozen in the dark as in RCs frozen
      under illumination. Furthermore, these interactions are completely consistent
      with those observed in RC crystals frozen in the dark. Thus, QA remains in its
      binding site with the same position and orientation upon reduction. This
      conclusion is consistent with the result of our orientation-resolving PELDOR
      experiments on transient P(.+) Q(A)(.-) radical pairs. However, these findings
      are incompatible with the recently proposed ~60 degrees  reorientation of Q(A)
      upon its photoreduction, as deduced from an analysis of Q-band quantum-beat
      oscillations (Heinen et al. J. Am. Chem. Soc. 2007, 129, 15935-15946). Such a
      large reorientation appears improbable, and our objections against this
      proposition are substantiated here in detail. Our results show that Q(A) is
      initially in an orientation that is favorable for its light-driven reduction.
      This diminishes the reorganization requirements for fast electron reduction and
      high quantum efficiency.

PMID- 21090819
TI  - Intercalation of a nonionic surfactant (C10E3) bilayer into a Na-montmorillonite
      clay.
AB  - A nonionic surfactant, triethylene glycol mono-n-decyl ether (C(10)E(3)),
      characterized by its lamellar phase state, was introduced in the interlayer of a
      Na-montmorillonite clay at several concentrations. The synthesized organoclays
      were characterized by small-angle X-ray scattering in conjunction with Fourier
      transform infrared spectroscopy and adsorption isotherms. Experiments showed that
      a bilayer of C(10)E(3) was intercalated into the interlayer space of the
      naturally exchanged Na-montmorillonite, resulting in the aggregation of the
      lyotropic liquid crystal state in the lamellar phase. This behavior strongly
      differs from previous observations of confinement of nonionic surfactants in
      clays where the expansion of the interlayer space was limited to two monolayers
      parallel to the silicate surface and cationic surfactants in clays where the
      intercalation of organic compounds is introduced into the clay galleries through
      ion exchange. The confinement of a bilayer of C(10)E(3) nonionic surfactant in
      clays offers new perspectives for the realization of hybrid nanomaterials, since
      the synthesized organoclays preserve the electrostatic characteristics of the
      clays, thus allowing further ion exchange while presenting at the same time a
      hydrophobic surface and a maximum opening of the interlayer space for the
      adsorption of neutral organic molecules of important size with functional
      properties.

PMID- 21090820
TI  - Molecular packing of functionalized fluorinated lipids in Langmuir monolayers.
AB  - Fluorinated amphipaths are a fascinating class of compounds, which, despite
      significant challenges associated with their syntheses, have found use across a
      number of areas of biotechnology. Applications range from the in vitro
      stabilization of membrane proteins to the development of enhanced stability
      intravenous drug and gene delivery systems. More recently, monolayer-forming
      fluorinated lipids have found use in the 2D crystallization of detergent
      solubilized hydrophobic or partially hydrophobic proteins at the air-water
      interface. In this study, we investigate the surface properties of a novel suite
      of monolayer forming, partially fluorinated lipids. These modular lipid
      structures contain a densely fluorinated insertion in the hydrocarbon tail and a
      synthetically modifiable headgroup. Analyses of surface-pressure area isotherms
      and X-ray reflectometry profiles reveal that the lipids spread into fluid
      monolayers and are more compressible than their non-fluorinated counterparts.
      Furthermore, the data support a model whereby the partially fluorinated chains of
      the lipid tails form a film which is fundamentally incompatible with detergents
      and other destabilizing amphipaths.

PMID- 21090821
TI  - Global and local expression of chirality in serine on the Cu{110} surface.
AB  - Establishing a molecular-level understanding of enantioselectivity and chiral
      resolution at the organic-inorganic interfaces is a key challenge in the field of
      heterogeneous catalysis. As a model system, we investigate the adsorption
      geometry of serine on Cu{110} using a combination of low-energy electron
      diffraction (LEED), scanning tunneling microscopy (STM), X-ray photoelectron
      spectroscopy (XPS), and near-edge X-ray absorption fine structure (NEXAFS)
      spectroscopy. The chirality of enantiopure chemisorbed layers, where serine is in
      its deprotonated (anionic) state, is expressed at three levels: (i) the molecules
      form dimers whose orientation with respect to the substrate depends on the
      molecular chirality, (ii) dimers of L- and D-enantiomers aggregate into
      superstructures with chiral (-1 ?2; 4 0) lattices, respectively, which are mirror
      images of each other, and (iii) small islands have elongated shapes with the
      dominant direction depending on the chirality of the molecules. Dimer and
      superlattice formation can be explained in terms of intra- and interdimer bonds
      involving carboxylate, amino, and beta-OH groups. The stability of the layers
      increases with the size of ordered islands. In racemic mixtures, we observe
      chiral resolution into small ordered enantiopure islands, which appears to be
      driven by the formation of homochiral dimer subunits and the directionality of
      interdimer hydrogen bonds. These islands show the same enantiospecific elongated
      shapes those as in low-coverage enantiopure layers.

PMID- 21090822
TI  - Self-assembly of virus particles on flat surfaces via controlled evaporation.
AB  - Dynamic self-assembly of nonvolatile solutes via controlled solvent evaporation
      has been exploited as a simple route to create a variety of hierarchically
      assembled structures. In this work, two glass slides were used to form a confined
      space in which a solution of a rodlike nanoparticle, tobacco mosaic virus (TMV),
      was evaporated to create large-scale stripe patterns. The height and width of the
      stripes are dependent on the TMV concentration. The large-scale-patterned
      surfaces can be applied to control surface hydrophobicity and direct the growth
      of bone marrow stromal cells. We systematically studied the effects of stripe
      width and height on surface hydrophobicity using optical microscopy, atomic force
      microscopy, and contact angle measurements. This technique offers a facile
      approach to form 2D patterns on a large surface from a wide range of proteins as
      well as other biomacromolecules.

PMID- 21090823
TI  - Thermoreversible hydroferrogels with tunable mechanical properties utilizing
      block copolymer mesophases as template.
AB  - Thermoreversible hydroferrogels (FGs) have been prepared via gelation of aqueous
      maghemite ferrofluids (FFs) using the triblock copolymer Pluronic P123 as
      gelator. In the investigated concentration range of 28-42 wt % P123, long-term
      stable homogeneous FGs can be prepared from FFs with a maximum maghemite content
      of 14 wt %. For higher FF concentrations up to 29 wt %, however, homogeneous FGs
      were formed only for gelator contents up to ca. 33 wt %. A combination of
      rheology and MU-DSC was applied as an alternative method to construct the P123
      phase diagram, without the need for visual methods or scattering techniques.
      Using this procedure, we could show that maghemite nanoparticles can be
      effectively templated by the cubic and hexagonal P123 mesophases in a
      concentration range of 33-38 wt % P123 and FF concentrations up to 14 wt %,
      respectively. Most importantly, the phase behavior and the corresponding phase
      transition temperatures of P123 were not significantly altered. As a result, the
      FGs show a reversible temperature-triggered transition from a cubic hard gel to a
      hexagonal gel, which is linked with a softening of the gel. Furthermore, this
      concept can be applied to template cobalt ferrite nanoparticle effectively, too.
      Magnetization experiments revealed that the superparamagnetic behavior of the
      maghemite nanoparticles, which show a Neel type relaxation, is not altered in the
      corresponding FGs. In contrast, FGs based on blocked cobalt ferrite nanoparticles
      show a hysteretic behavior, which indicates a strong mechanical coupling between
      the P123 mesophase and the magnetic nanoparticles.

PMID- 21090824
TI  - Mechanical characterization and pH response of fibril-reinforced microcapsules
      prepared by layer-by-layer adsorption.
AB  - Despite the fair number of microencapsulation principles that have been
      developed, the actual protection and targeted delivery of sensitive ingredients
      remains a challenge in the food industry. A suitable technique should use food
      grade and inexpensive materials, and ensure tight control over the capsule size
      and release trigger mechanism. For example, encapsulates may need to survive the
      low pH of the stomach to release their contents in the neutral environment of the
      small intestine. In this work we present layer-by-layer (LbL) microcapsules
      assembled from whey protein isolate (WPI), high-methoxyl pectin (HMP) and WPI
      fibrils. The narrow size distribution of these capsules is determined by the oil
      in-water droplets used as templates, and their mechanical properties and pH
      response can be tuned by the number of layers adsorbed. Capsules with more than
      eight layers have a mechanical strength comparable to chemically cross-linked
      polymer capsules, because of the reinforcement by the WPI-fibrils in combination
      with the shell completion. Typically, capsules with five layers survive pH 2 for
      more than 2 h, but dissolve within 30 min at pH 7. At higher number of layers,
      the capsules are even more stable. Contrary to other encapsulates, these capsules
      can be dried and are suitable for application in dry products.

PMID- 21090825
TI  - Effects of temperature and physical state on heterogeneous oxidation of oleic
      acid droplets with ozone.
AB  - The heterogeneous reactions of pure micrometer-sized oleic acid droplets with
      ozone were studied as a function of temperature and physical state. Oxidation
      reactions were monitored using attenuated total reflectance Fourier transform
      infrared spectroscopy (ATR-FT-IR) and UV-vis spectrometry. Variations in droplet
      morphology due to the extent of oxidation were monitored using an optical
      microscope. Oleic acid droplets were maintained in either solid or liquid state
      at 9.0  degrees C. The physical state of the aerosol was determined from the IR
      absorbance spectra. Oxidation of solid state oleic acid with ozone at 9.0 
      degrees C was rapidly converted to the liquid state, which was most likely due to
      the presence of oxidation products on the surface of the droplets. The fast
      melting process that resulted from exposure of solid-phase droplets to ozone
      produced an oxidation rate similar to that for liquid-phase droplets exposed to
      ozone at the same temperature. Analysis of the carboxylic IR absorbance ratio for
      esters vs carboxylic acids indicates that the larger ester C?O-to-carboxylic acid
      C?O ratios at higher temperature appeared to correspond to the production of
      alpha-acyloxyalkyl hydroperoxide oligomers and polymers. The wide variation in
      product yields will result in vastly different physical properties of aerosol
      particles under different ambient environmental conditions.

PMID- 21090826
TI  - Rate control with ivabradine: angina pectoris and beyond.
AB  - The importance of heart rate in human health and disease has been well known to
      clinicians for quite some time. Recent epidemiologic studies have further
      strengthened this concept. Modulation of heart rate by pharmacologic as well as
      non-pharmacologic means has affected cardiovascular mortality and morbidity in
      various trials and observational studies. Conventional rate-control agents, such
      as beta-adrenoceptor antagonists (beta-blockers), calcium channel blockers, and
      digoxin, have contributed greatly to the management of various diseases where
      heart-rate reduction is required; however, these agents have effects beyond rate
      control that may be unacceptable. Ivabradine has recently been recognized as a
      pure heart-rate-reducing agent and is being extensively studied. It is the latest
      addition to the class of drugs used to control angina. It is indicated in cases
      of beta-blocker intolerance or when beta-blockers fail to achieve a heart rate of
      <60 beats/min. The pure heart-rate-reducing effect of ivabradine has also been
      reported in smaller studies and anecdotal case reports. The theoretical
      possibilities of the utility of ivabradine are many and have opened up a whole
      new field of research for the future. The BEAUTIFUL trial enrolled approximately
      10,000 patients with coronary artery disease (CAD) and left ventricular
      dysfunction, with the aim of assessing the effect of ivabradine versus atenolol
      on various cardiovascular outcomes. Although ivabradine failed to achieve
      favorable results for primary endpoints, it appeared effective in achieving a
      favorable secondary endpoint in a subgroup of patients who had a heart rate of
      >70 beats/min. Other large trials are also underway to assess the effects of
      ivabradine on heart failure, acute coronary syndromes, CAD, and other
      cardiovascular disorders. In this review, we discuss the pharmacologic basis of
      the action of ivabradine and its role in angina control, as well as in other
      conditions being actively studied or in which a role for ivabradine has been
      hypothesized.

PMID- 21090828
TI  - Aliskiren in the management of hypertension.
AB  - Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor
      antagonists (angiotensin receptor blockers) have been shown to be effective drugs
      in the management of hypertension and to have beneficial effects along the
      cardiovascular continuum. However, due to compensatory mechanisms, both of these
      types of agent increase plasma renin activity, which has been reported to have
      deleterious effects on patient outcomes. Aliskiren is the first nonpeptide orally
      administered direct renin inhibitor available on the market. Reported data have
      shown that aliskiren effectively reduces BP alone or in combination with other
      antihypertensive agents, and has a good tolerability profile. Moreover, this
      agent reduces plasma renin activity, which in theory could have additional
      clinical benefits. However, clinical trials analyzing the effects of aliskiren on
      mortality are still ongoing.

PMID- 21090829
TI  - Impact of bisphosphonates on the risk of atrial fibrillation.
AB  - Osteoporosis is a major public health problem resulting in significant morbidity,
      mortality, and utilization of healthcare resources. Bisphosphonates are the most
      widely prescribed drugs for increasing bone mass and preventing osteoporosis
      related fractures. Although these drugs have proven efficacy and are generally
      considered safe, a clinical trial of once-yearly zoledronic acid reported an
      unexpected increase in the risk of cardiac arrhythmias, primarily due to serious
      atrial fibrillation (AF). Subsequently, a post hoc analysis of another clinical
      trial reported a nonsignificant trend toward an increased risk of serious AF.
      Based on these concerns, the US FDA issued a cautionary advisory and is
      conducting an ongoing safety review. A major limitation of the clinical trials
      was the fact that none were designed or powered to evaluate arrhythmia endpoints.
      In search of more definitive answers, several observational studies using both
      population-based cohort and case-control designs have attempted to verify this
      association. However, only two studies, one cohort and one case-control study,
      have found a positive association, while six additional studies have reported
      negative findings. While most of the observational studies attempted to control
      for confounders, the chosen variables have varied considerably, and other key
      potential confounders such as smoking were not controlled for in any of the
      studies. Because the occurrence of AF events in the studies was relatively low,
      four meta-analyses have been conducted to increase sample size by using pooled
      data from multiple studies. Again, results have been inconsistent, with two of
      the analyses reporting a significant increase in serious AF and two finding no
      association. Additionally, no direct evidence has identified any underlying
      mechanism to explain an increased arrhythmia risk with bisphosphonate therapy.
      However, several possible mechanisms have been proposed, including an activated
      inflammatory state, altered electrolytes impacting cardiac conduction, and long
      term atrial structural changes. Due to the widespread use of bisphosphonates in a
      population for whom the baseline risk of AF also increases with advancing age,
      further prospective assessment of this possible association is clearly warranted.
      If an association does exist between bisphosphonates and an increased risk for
      AF, several additional questions will need to be answered including impact of
      baseline risk, the time course for increased risk, relationship to drug dose, and
      whether or not this represents a drug-class adverse effect. Until definitive
      evidence is available, clinicians will continue to have to make clinical
      judgments based on the available and often inconsistent evidence to date. To
      provide further perspective on this possible association, we performed a
      systematic search of the PubMed database from 1966 to 30 June 2010, drug
      regulatory websites, and drug manufacturer websites. In this review we summarize
      the findings from clinical trials, observational studies, and meta-analyses
      evaluating the risk of AF following bisphosphonate exposure, and discuss possible
      mechanisms that could explain an increased risk.

PMID- 21090830
TI  - The cost effectiveness of statin therapies in Spain in 2010, after the
      introduction of generics and reference prices.
AB  - BACKGROUND: HMG-CoA reductase inhibitors (statins) are the first-line drugs for
      use in the reduction of low-density lipoprotein cholesterol (LDL-C) levels and
      prevention of coronary heart disease (CHD) in patients with hypercholesterolemia.
      Generic statins could change the cost effectiveness of statin therapies in Spain,
      and more population groups could be included in the recommendations for reduction
      of cholesterol levels based on cost effectiveness. OBJECTIVES: The objectives of
      this study were: (i) to assess the cost effectiveness of available statins for
      the reduction of LDL-C levels in Spain in 2010, after the introduction of
      generics and reference prices; (ii) to assess the cost effectiveness of
      combination therapy using a statin plus cholestyramine or ezetimibe; and (iii) to
      estimate the mean cost per patient to achieve National Cholesterol Education
      Program (Adult Treatment Panel-III) therapeutic objectives. METHODS: The
      following treatments were evaluated: rosuvastatin 5-20 mg/day; atorvastatin,
      simvastatin, and pravastatin 10-40 mg/day; lovastatin and fluvastatin 20-80
      mg/day; and combination therapy with a statin plus either cholestyramine 12-24
      g/day or ezetimibe 10 mg/day. The cost effectiveness was evaluated in terms of
      cost per percentage point reduction in LDL-C, comparing the annual treatment
      costs with the effectiveness in reducing LDL-C. Treatment costs included those
      for medications (2010 wholesale prices), control measures, and treatment of
      adverse drug effects. The effectiveness of statins was estimated by developing a
      meta-analysis of clinical trials published between 1993 and 2005 that met several
      inclusion criteria. Average and incremental cost-effectiveness ratios were
      calculated to assess the efficiency of individual statin and combination
      therapies in reducing LDL-C levels. RESULTS: The effectiveness in terms of
      percentage reduction in LDL-C ranged from 19% for pravastatin 10 mg/day to 55%
      for atorvastatin 80 mg/day. Annual treatment costs ranged from Euro 189.7 for
      simvastatin 10 mg/day to Euro 759.3 for atorvastatin 80 mg/day. The cost
      effectiveness ratios, in terms of cost per percentage point reduction in LDL-C,
      were: Euro 6 for simvastatin, Euro 10-12 for rosuvastatin, Euro 10 for
      lovastatin, Euro 13-16 for atorvastatin, Euro 13-14 for fluvastatin, and Euro 14
      20 for pravastatin. Rosuvastatin + ezetimibe, simvastatin + ezetimibe, and
      atorvastatin + ezetimibe were the most cost-effective combination therapies for
      reducing LDL-C levels. Rosuvastatin was the most cost-effective statin for
      achieving the LDL-C therapeutic goal in patients at high risk for CHD, with a
      mean cost per patient of Euro 516. Simvastatin was the most cost-effective statin
      to achieve the LDL-C goal in patients with moderate or low CHD risk, with a cost
      per patient of Euro 217 and Euro 190, respectively. CONCLUSION: Rosuvastatin
      should be the first-choice agent in patients with high CHD risk, while
      simvastatin should be the first choice in patients with moderate or low risk. The
      addition of ezetimibe to rosuvastatin, simvastatin, or atorvastatin should be the
      preferred combination therapies when greater LDL-C reductions are required. The
      cost effectiveness of all statin therapies has increased in Spain after the
      introduction of generic statins and reference prices.

PMID- 21090831
TI  - Rosuvastatin: a review of its use in the prevention of cardiovascular disease in
      apparently healthy women or men with normal LDL-C levels and elevated hsCRP
      levels.
AB  - Rosuvastatin (Crestor(r)) is an HMG-CoA reductase inhibitor (statin) that has
      both lipid-lowering and anti-inflammatory effects. The drug has various
      indications in the US, including the primary prevention of cardiovascular disease
      (CVD) in patients with no clinical evidence of coronary heart disease who are at
      increased risk of CVD based on their age, a high-sensitivity C-reactive protein
      (hsCRP) level of >=2 mg/L, and at least one other CVD risk factor. The efficacy
      of rosuvastatin in apparently healthy women (aged >=60 years) or men (aged >=50
      years) with normal low-density lipoprotein cholesterol (LDL-C) levels and
      elevated hsCRP levels was demonstrated in the large, randomized, double-blind,
      multinational, JUPITER trial. Relative to placebo, rosuvastatin 20 mg once daily
      for a median follow-up of 1.9 years significantly reduced the occurrence of first
      major cardiovascular events in this trial (primary endpoint). A between-group
      difference in favor of rosuvastatin was also demonstrated for various other
      endpoints, including overall deaths and the nonatherothrombotic endpoint of
      venous thromboembolism. Rosuvastatin remained more effective than placebo when
      primary endpoint results were stratified according to various baseline factors,
      including in patient subgroups thought to be at low risk of CVD. In addition,
      rosuvastatin was associated with reductions in LDL-C and hsCRP levels, and these
      reductions appeared to occur independently of each other. The greatest clinical
      benefit was observed in rosuvastatin recipients achieving an LDL-C level of <1.8
      mmol/L (<70 mg/dL) and an hsCRP level of <2 mg/L or, even more so, <1 mg/L.
      Rosuvastatin was well tolerated in the JUPITER trial, with most adverse events
      being mild to moderate in severity. Myalgia, arthralgia, constipation, and nausea
      were the most commonly occurring treatment-related adverse events, and the
      incidence of monitored adverse events and laboratory measurements was generally
      similar in the rosuvastatin and placebo groups. It is not yet known whether the
      mechanism of benefit of rosuvastatin is via lipid effects, anti-inflammatory
      effects, or a mixture of both, and the use of rosuvastatin solely on the basis of
      elevated hsCRP levels is controversial. Nonetheless, the drug remains an
      important pharmacologic option in the prevention of CVD, and has demonstrated
      efficacy in preventing major cardiovascular events in apparently healthy women
      (aged >=60 years) or men (aged >=50 years) with normal LDL-C levels and elevated
      hsCRP levels.

PMID- 21090832
TI  - Telmisartan/amlodipine: single-pill combination in hypertension.
AB  - Telmisartan/amlodipine is a single-pill combination of telmisartan, an
      angiotensin II receptor antagonist, and amlodipine, a dihydropyridine calcium
      channel antagonist, which is taken orally once daily for the treatment of
      hypertension. In the US and the EU, single-pill telmisartan/amlodipine can be
      used as a replacement for separate telmisartan and amlodipine tablets, and by
      patients not achieving BP goals with amlodipine monotherapy. In addition, the US
      indication includes patients not achieving BP goals with telmisartan (or another
      angiotensin II receptor antagonist or calcium channel antagonist other than
      amlodipine) alone, and as initial therapy in patients considered likely to
      require multiple drugs to achieve their BP goals. In an 8-week, randomized,
      double-blind, factorial-design, placebo-controlled, multicenter study in adult
      patients with hypertension (n = 1461), mean DBP was reduced from baseline to a
      significantly greater extent in recipients of telmisartan 40 or 80 mg/day plus
      amlodipine 5 or 10 mg/day than in those receiving equivalent dosages of
      telmisartan or amlodipine monotherapy. Single-pill telmisartan/amlodipine
      recipients had significantly greater reductions in BP than telmisartan or
      amlodipine monotherapy recipients in an 8-week, randomized, double-blind,
      multicenter study in adult patients with severe hypertension (n = 858), and in
      four 8-week, randomized, double-blind, multicenter trials in patients who had not
      responded to amlodipine (n = 1097, 947, and 531) or telmisartan (n = 314)
      monotherapy. Telmisartan/amlodipine was generally well tolerated in clinical
      trials, including two 36-week follow-up studies.

PMID- 21090833
TI  - Vorapaxar.
AB  - Merck & Co. is developing vorapaxar (SCH 530348), a thrombin receptor antagonist,
      for the prevention and treatment of arterial thrombosis. Vorapaxar is currently
      being evaluated in two large-scale multinational phase III trials (TRA*CER and
      TRA 2 degrees P-TIMI 50) for the treatment and prevention of cardiac events in
      almost 30,000 patients with acute coronary syndromes and those with prior
      myocardial infarction or stroke, as well as patients with acute coronary syndrome
      and those with peripheral arterial disease. This review discusses the development
      history and scientific profile of this new compound.

PMID- 21090836
TI  - Epidemiology and management of alcohol dependence in individuals with post
      traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is a chronic and disabling psychiatric
      disorder with an estimated lifetime prevalence of 7.8%. Co-morbid alcohol
      dependence is a common clinical occurrence with important clinical
      considerations. For example, in individuals with both PTSD and alcohol
      dependence, the symptoms of PTSD tend to be more severe, and there is evidence
      that these individuals are more prone to alcohol use relapse than non-co-morbid
      individuals. Co-morbidity of PTSD and alcohol dependence is also associated with
      a higher rate of psychosocial and medical problems and higher utilization of
      inpatient hospitalization than either disorder alone. This article highlights the
      epidemiology of alcohol dependence in PTSD and reviews the evidence for effective
      treatments. Management of these individuals requires an understanding of the
      epidemiology and an awareness of treatment interventions, which include both
      psychosocial treatments (e.g. Seeking Safety, Concurrent Treatment of PTSD and
      Cocaine Dependence, Transcend, Trauma Recovery and Empowerment Model) and
      pharmacotherapy (e.g. selective serotonin reuptake inhibitors [SSRIs] and
      topiramate). Effective treatment of co-morbid PTSD and alcohol dependence may
      include a combination of these psychosocial and pharmacological interventions.
      The key element seems to be to ensure an adequate intervention for each disorder
      administered collaboratively.

PMID- 21090835
TI  - Preventative strategies for early-onset bipolar disorder: towards a clinical
      staging model.
AB  - Bipolar disorder is a chronic and typically recurring illness with significant
      psychosocial morbidity. Although the aetiological factors that contribute to the
      onset of mania, and by definition bipolar I disorder, are poorly understood, it
      most commonly occurs during the adolescent period. Putative risk factors for
      developing bipolar disorder include having a first-degree relative with a mood
      disorder, physical/sexual abuse and other psychosocial stressors, substance use
      disorders, psychostimulant and antidepressant medication exposure and omega-3
      fatty acid deficiency. Prominent prodromal clinical features include episodic
      symptoms of depression, anxiety, hypomania, anger/irritability and disturbances
      in sleep and attention. Because prodromal mood symptoms precede the onset of
      mania by an average of 10 years, and there is low specificity of risk factors and
      prodromal features for mania, interventions initiated prior to onset of the
      disorder (primary prevention) or early in the course of the disorder (early or
      secondary prevention) must be safe and well tolerated upon long-term exposure.
      Indeed, antidepressant and psychostimulant medications may precipitate the onset
      of mania. Although mood stabilizers and atypical antipsychotic medications
      exhibit efficacy in youth with bipolar I disorder, their efficacy for the
      treatment of prodromal mood symptoms is largely unknown. Moreover, mood
      stabilizers and atypical antipsychotics are associated with prohibitive treatment
      emergent adverse effects. In contrast, omega-3 fatty acids have neurotrophic and
      neuroprotective properties and have been found to be efficacious, safe and well
      tolerated in the treatment of manic and depressive symptoms in children and
      adolescents. Together, extant evidence endorses a clinical staging model in which
      subjects at elevated risk for developing mania are treated with safer
      interventions (i.e. omega-3 fatty acids, family-focused therapy) in the prodromal
      phase, followed by pharmacological agents with potential adverse effects for
      nonresponsive cases and secondary prevention. This approach warrants evaluation
      in prospective longitudinal trials in youth determined to be at ultra-high risk
      for bipolar I disorder.

PMID- 21090837
TI  - Pharmacokinetic variability of long-acting stimulants in the treatment of
      children and adults with attention-deficit hyperactivity disorder.
AB  - Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies
      for attention-deficit hyperactivity disorder, a common neurobehavioural disorder
      in children and adults. A number of long-acting stimulant formulations have been
      developed with the aim of providing once-daily dosing, employing various means to
      extend duration of action, including a transdermal delivery system, an osmotic
      release oral system, capsules with a mixture of immediate- and delayed-release
      beads, and prodrug technology. Coefficients of variance of pharmacokinetic
      measures can estimate the levels of pharmacokinetic variability based on the
      measurable variance between different individuals receiving the same dose of
      stimulant (interindividual variability) and within the same individual over
      multiple administrations (intraindividual variability). Differences in
      formulation clearly impact pharmacokinetic profiles. Many medications exhibit
      wide interindividual variability in clinical response. Stimulants with low levels
      of inter- and intraindividual variability may be better suited to provide
      consistent levels of medication to patients. The pharmacokinetic profile of
      stimulants using pH-dependent bead technology can vary depending on food
      consumption or concomitant administration of medications that alter gastric pH.
      While delivery of methylphenidate with the transdermal delivery system would be
      unaffected by gastrointestinal factors, intersubject variability is nonetheless
      substantial. Unlike the beaded formulations and, to some extent (when considering
      total exposure) the osmotic-release formulation, systemic exposure to amfetamine
      with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected
      by such factors, likely owing to its dependence on systemic enzymatic cleavage of
      the precursor molecule, which occurs primarily in the blood involving red blood
      cells. The high capacity but as yet unidentified enzymatic system for conversion
      of lisdexamfetamine dimesylate may contribute to its consistent pharmacokinetic
      profile. The reasons underlying observed differential responses to stimulants are
      likely to be multifactorial, including pharmacodynamic factors. While the use of
      stimulants with low inter- and intrapatient pharmacokinetic variability does not
      obviate the need to titrate stimulant doses, stimulants with low intraindividual
      variation in pharmacokinetic parameters may reduce the likelihood of patients
      falling into subtherapeutic drug concentrations or reaching drug concentrations
      at which the risk of adverse events increases. As such, clinicians are urged both
      to adjust stimulant doses based on therapeutic response and the risk for adverse
      events and to monitor patients for potential causes of pharmacokinetic
      variability.

PMID- 21090838
TI  - Examining the clinical utility of lacosamide: pooled analyses of three phase
      II/III clinical trials.
AB  - BACKGROUND: Lacosamide is an antiepileptic drug (AED) approved for the adjunctive
      treatment of partial-onset seizures in adults. Completed phase II/III clinical
      trials of lacosamide provide a valuable opportunity to evaluate clinically
      relevant aspects of the resulting large patient pool. OBJECTIVE: To provide
      insight into the clinical utility of lacosamide by performing a priori-defined
      and post hoc analyses on a large, pooled patient population. STUDY DESIGN: Pooled
      data from three randomized, double-blind, multicentre, placebo-controlled phase
      II/III trials. PATIENTS: Adult patients with partial-onset seizures with or
      without secondary generalization (N = 1294). INTERVENTION: Four- to six-week
      titration followed by 12-week maintenance treatment with lacosamide (Vimpat(r))
      200, 400 or 600 mg/day or placebo. MAIN OUTCOME MEASURE: A priori-defined primary
      efficacy variables for the pooled analysis were change in seizure frequency per
      28 days and the proportion of patients experiencing a >=50% reduction in seizure
      frequency (50% responder rate) from Baseline to the Maintenance Phase; a priori
      defined secondary efficacy variables were the proportion of patients achieving a
      >=75% reduction in seizure frequency from Baseline to the Maintenance Phase (75%
      responder rate), the proportion of Maintenance Phase completers remaining seizure
      free throughout the entire Maintenance Phase and the percentage of seizure-free
      days during the Maintenance Phase for patients entering the Maintenance Phase.
      The pooled analyses of the change in seizure frequency, and 50% and 75% responder
      rates were performed with an intent-to-treat (ITT) approach, including all
      patients receiving at least one dose of trial medication and having at least one
      post-baseline efficacy assessment. Similar analyses of the two primary efficacy
      variables and 75% responder rates were also performed using a modified ITT
      population (ITTm) that included ITT patients who entered the Maintenance Phase.
      Additional post hoc efficacy analyses were an evaluation of onset of efficacy and
      assessment of efficacy in patients grouped by prior surgical history and
      individual concomitant AED use. In addition, pharmacokinetic-pharmacodynamic
      modelling was performed, and safety data were assessed. RESULTS: In this pooled
      analysis of 1294 difficult-to-treat patients, all three dosages of lacosamide
      (200, 400 and 600 mg/day) showed a significant improvement compared with placebo
      for median percent seizure reduction (ITT and ITTm; p < 0.05 for 200 mg/day, p <
      0.001 for 400 and 600 mg/day), as well as for 50% responder rate (ITT and ITTm; p
      < 0.05 for 200 mg/day, p < 0.001 for 400 and 600 mg/day). Evaluation of 75%
      responder rate in the phase II/III pooled population showed that a significantly
      higher proportion of patients randomized to lacosamide 400 or 600 mg/day achieved
      a >=75% reduction in seizure frequency compared with placebo (ITT and ITTm; p <
      0.001); statistical significance was not observed for lacosamide 200 mg/day (ITT
      and ITTm). A total of 2.7%, 3.3% and 4.8% of patients completing the Maintenance
      Phase in the lacosamide 200, 400 and 600 mg/day groups, respectively, experienced
      no seizures throughout the entire Maintenance Phase (placebo group = 0.9%). The
      mean change from baseline in the percentage of seizure-free days in patients
      entering the Maintenance Phase for the phase II/III pool was 8.0%, 11.6% and
      14.7% with lacosamide 200 (p = 0.077), 400 (p < 0.001) and 600 (p < 0.001) mg/day
      groups, respectively, compared with 6.1% in the placebo group. The onset of
      efficacy relative to placebo was evident by the first week of treatment with
      lacosamide. Efficacy was similar in lacosamide-treated patients reporting prior
      surgical intervention for epilepsy compared to lacosamide-treated patients with
      no prior surgical intervention. Lacosamide showed a reduction in seizures,
      regardless of the concomitant AEDs used. The preferred pharmacokinetic
      pharmacodynamic model (E(max)) supported the therapeutic dose range of
      lacosamide, and no additional safety concerns were identified in the phase II/III
      pooled analysis. CONCLUSIONS: Results of these a priori-defined and post hoc
      pooled data analyses from phase II/III trials demonstrate that lacosamide
      effectively reduces seizures in patients at all three dosages evaluated with an
      early onset of efficacy, regardless of patient surgical history and concomitant
      AED regimen.

PMID- 21090839
TI  - A pooled analysis of lacosamide clinical trial data grouped by mechanism of
      action of concomitant antiepileptic drugs.
AB  - BACKGROUND: Lacosamide, a new antiepileptic drug (AED) with a different
      pharmacological action that enhances sodium channel slow inactivation, is
      approved for the adjunctive treatment of partial-onset seizures in adults.
      Previous analyses of pooled phase II/III trials have demonstrated that lacosamide
      provides additional efficacy when added to a broad range of AEDs. OBJECTIVE: To
      further evaluate the efficacy and safety of lacosamide by grouping patients based
      upon the sodium channel-blocking properties of their concomitant AEDs. STUDY
      DESIGN: Post hoc exploratory analyses were performed on pooled data in which
      patients were grouped based upon inclusion or non-inclusion of at least one
      'traditional' sodium channel-blocking AED (defined as carbamazepine, lamotrigine,
      oxcarbazepine and phenytoin derivatives) as part of their concomitant AED
      regimen. SETTING: Data pooled from previously conducted phase II/III clinical
      trials of lacosamide. PATIENTS: Adult patients with partial-onset seizures with
      or without secondary generalization (N = 1308). INTERVENTION: Four- to six-week
      Titration Phase followed by 12-week maintenance treatment with adjunctive
      lacosamide (Vimpat(r)) [200, 400 or 600 mg/day] or placebo. MAIN OUTCOME MEASURE:
      Efficacy variables included change in seizure frequency per 28 days and the
      proportion of patients experiencing a >=50% reduction in seizure frequency (50%
      responder rate) from Baseline to the Maintenance Phase. The proportion of
      patients experiencing a >=75% reduction in seizure frequency from Baseline to the
      Maintenance Phase (75% responder rate) was also assessed. Safety parameters
      assessed were treatment-emergent adverse events (TEAEs) and discontinuation due
      to TEAEs. Additional safety assessments were changes in ECG and laboratory
      parameters as well as vital signs (including bodyweight). RESULTS: Of 1308
      patients in the pooled phase II/III population, the majority (82%) were using at
      least one 'traditional' sodium channel-blocking concomitant AED. In this subgroup
      of patients, adjunctive lacosamide showed significant reductions in seizure
      frequency (p < 0.01, all dosages) and significantly greater 50% and 75% responder
      rates (p < 0.01 for 400 mg/day; p < 0.01 [50% responder rate] and p < 0.05 [75%
      responder rate] for 600 mg/day) compared with placebo; these effects were similar
      to the results seen in the pooled phase II/III population. TEAEs and
      discontinuations due to TEAEs in this subgroup were dose related and similar to
      the pooled phase II/III population. In the remaining subgroup of patients, i.e.
      those not taking 'traditional' sodium channel-blocking AEDs as part of their
      concomitant AED regimen (n = 231; 18%), a pronounced, dose-related seizure
      reduction was observed with lacosamide (p < 0.01, 400 and 600 mg/day for median
      percent seizure reduction and 50% or 75% responder rates). Also in this group,
      incidences of TEAEs were low, and discontinuations due to TEAEs did not appear to
      increase with dose. Analyses of ECG, laboratory and vital signs (including
      bodyweight) assessments did not identify abnormalities in either subgroup that
      were outside of the known safety profile of lacosamide observed in the pooled
      phase II/III population. CONCLUSION: In this post hoc exploratory analysis,
      adjunctive lacosamide demonstrated significant seizure reduction over placebo
      regardless of the inclusion of 'traditional' sodium channel blockers in the
      concomitant AED regimen. Future prospective studies evaluating single AED
      combinations (e.g. lacosamide plus one other drug) are needed to better evaluate
      the potential for additive or synergistic effects of lacosamide in combination
      with AEDs not considered 'traditional' sodium channel blockers.

PMID- 21090840
TI  - A systematic review to assess the policy-making relevance of dementia cost-of
      illness studies in the US and Canada.
AB  - A systematic review of dementia cost-of-illness (COI) studies in the US and
      Canada was conducted to explore the policy-making relevance of these studies.
      MEDLINE, CINAHL, EconLit, AMED and the Cochrane Library were searched from
      inception to March 2010 for English-language COI articles. Content analysis was
      used to extract common themes about dementia cost from the conclusions of
      articles that passed title, abstract and full-text screening. These themes
      informed our exploration of the policy-making relevance of COI studies in
      dementia. The literature search retrieved 961 articles and data were extracted
      from 46 articles. All except three articles reported data from the US; 27
      articles included Alzheimer's dementia only. Common themes pertained to general
      observations about dementia cost, cost drivers in dementia, caregiver cost, items
      that may lower dementia cost, social service cost, Medicare and Medicaid cost,
      and cost comparisons with other diseases. The common themes suggest policy
      oriented research for the future. However, the extracted COI studies were
      typically not conducted for policy-making purposes and they did not commonly
      provide prescriptive policy options. Researchers and policy makers need to
      consider whether the optimal research focus in dementia should be on programme
      evaluations instead of more COI studies.

PMID- 21090841
TI  - New anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoid
      malignancies.
AB  - Over the last few years, new generations of anti-CD20 monoclonal antibodies
      (mAbs) have been developed for potential benefits over the classical, first
      generation mAb rituximab. Compared with rituximab, new mAbs have enhanced
      antitumor activity resulting from increased complement-dependent cytotoxicity
      (CDC) and/or antibody-dependent cellular cytotoxicity (ADCC) and increased Fc
      binding affinity for the low-affinity variants of the FcgammaRIIIa receptor
      (CD16) on immune effector cells. The second-generation mAbs, which include
      ofatumumab, veltuzumab, and ocrelizumab, are humanized or fully human to reduce
      immunogenicity, but with an unmodified Fc region. Ofatumumab is a fully human
      anti-CD20 IgG1 mAb in clinical development for hematological malignancies and
      autoimmune diseases. Ofatumumab specifically recognizes an epitope encompassing
      both the small and large extracellular loops of CD20 molecule, and is more
      effective than rituximab at CDC induction and killing target cells. Veltuzumab
      (IMMU-106, hA20) is a humanized anti-CD20 mAb with complementarity-determining
      regions similar to rituximab. This antibody has enhanced binding avidities and a
      stronger effect on CDC compared with rituximab. Ocrelizumab is a humanized mAb
      with the potential for enhanced efficacy in lymphoid malignancies compared with
      rituximab due to increased binding affinity for the low-affinity variants of the
      FcgammaRIIIa receptor. The third-generation mAbs are also humanized mAbs, but in
      addition they have an engineered Fc to increase their binding affinity for the
      FcgammaRIIIa receptor. The third-generation mAbs include AME-133v, PRO131921 and
      GA-101. AME-133v (LY2469298) is a type I, humanized IgG1 mAb with enhanced
      affinity for FcgammaRIIIa receptor and an enhanced ADCC activity compared with
      rituximab. PRO131921 is a humanized anti-CD20 mAb engineered to have improved
      binding to FcgammaRIIIa and better ADCC compared with rituximab. GA-101
      (RO5072759) is a fully humanized, type II, IgG1 mAb derived from humanization of
      the parental B-Ly1 mouse antibody and subsequent glycoengineering using
      GlycoMab(r) technology. GA-101 was designed for enhanced ADCC and superior direct
      cell-killing properties, in comparison with currently available type I
      antibodies. TRU-015 is a small modular immunopharmaceutical (SMIP) derived from
      key domains of an anti-CD20 antibody. TRU-015 represents a novel biological
      compound that retains Fc-mediated effector functions and is smaller than mAbs. In
      this article we review data on new anti-CD20 mAbs that are potentially useful in
      the treatment of lymphoid malignancies.

PMID- 21090842
TI  - [Conscientious objection of health personnel in the recent Organic Law 2/2010,
      about sexual and reproductive health and voluntary interruption of pregnancy].
AB  - The main goal of the paper is to analyse and evaluate the recent Organic Law
      2/2010, and its prescriptions referring to the conscientious objection of health
      personnel in relation to the voluntary interruption of pregnancy. The paper
      starts studying conscientious objection: its raison d'etre, its delimitation, its
      recognition by the Spanish regulation. Further on, the paper focuses on the
      article 19.2 degrees  of the Organic Law 2/2010, underlining on the one hand the
      positive aspects (such as the formal requirements for the objection), and on the
      other hand the negative ones (such as suspicion over objectors).

PMID- 21090843
TI  - [An approach to abortion and immigration in Spain. The social economic value of
      the human life].
AB  - This paper enters the analysis of the phenomenon of the abortion in Spain, across
      the study of the reasons of his practices in the group of immigrant women
      resident in Murcia. The following aims appear are: a) know the prevalence of
      abortions in the immigrant population of an urban center of primary care health
      in the state of Murcia, b) know the personal attitude before this population's c)
      analized abortion this population's socio-economic and religious characteristics
      and to value their possible relationship with the abortion. The material and
      method used form a descriptive traverse study, carried out in primary care
      (Center of primary care San Andres-state of Murcia) carried out during the months
      of June to December of 2007. 230 women were included. The collection of data was
      made by means of interview clinic carrying out a survey semistructured with open
      and closed questions, in total 14 items, enlarged to 23 items in case one
      declares voluntary abortions. The Results show us as the fundamental motives for
      those who are aborted they were the lack of economic means, the disadvantages for
      his personal projects and the pressure on the part of his pair or family. The
      conclusions, force first, from the bioethic reflection, to the denunciation of
      the political- social inaction with regard to the abortion and the ideological
      manipulation of the socioeconomic reasons of the same practices; and secondly, to
      the promotion of networks of help to the embarrassed woman and to the public
      defense of the absolute value of the human life.

PMID- 21090844
TI  - [Bioethical analysis in pregnancy's Jehova Witnesess and transfusion refusal].
AB  - In Mexico, Jehovah's witnesses present letters to their doctors that exonerate
      them in case of a patient's decease if hemotherapy was not applied. Although
      those letters have no legal validity in Mexico, this topic is a hot spot for
      debate, especially when dealing with competent adults. Bibliography exists, both
      pro and against this posture, but, an empty gap is observed in the case of
      pregnancy. With pregnancy, we doctors, find ourselves, both in the medical and
      ethical area, upon two patients: mother and son. Doctors have the same
      therapeutical responsibilities upon them. What alternatives would be presented in
      our country if the Jehovah's Witness's transfusional negative was accepted, and
      we had a pregnant patient in the need of one? Juridically, the acceptance of
      adult Jehovah's Witness's thesis is included under the acceptance of moral
      objection, however: 1) Moral objection is not a general right, but exceptional,
      with a justified reason. 2) It can not produce any possible harm to third
      parties. The conflict of interest mother/fetus in hemotherapeutical urgencies can
      be tackled under three possibilities: a) Total respect to mother's autonomy.
      RESULT: high death possibility for both mother and fetus. b) Not to respect
      mother's autonomy. RESULT: high life possibilities for mother and fetus. c)
      Respect mother's negative to be transfunded and to operate maneuvers for fetal
      rescue. RESULT: high death possibilities for mother and relative life
      possibilities for fetal life. The physician, when dealing with a pregnant woman,
      has a responsibility with two patients. As a first intention, the doctor should
      always offer a proper handle of the case, according to the pregnant patient's
      beliefs as much as possible, nevertheless he must never forget his compromise to
      the embryo's/fetus's life.

PMID- 21090845
TI  - [Julian Marias. A responsable answer to the problem of abortion].
AB  - The main objective of this text is to offer a solution to the present debate
      about abortion. Two experts could represent the most important opinions about
      this topic. On the one hand, Julian Marias, the Spanish philosopher, who thinks
      that abortion is always a crime against human life and dignity. On the other
      hand, we will find a different view in the works of Peter Singer in an article of
      M. A. Warren. The reasons from one and another will be shown to find a solution
      to this intricate controversy.

PMID- 21090846
TI  - [Usefulness of the Delphi method for reaching consensus in the allocation of
      deceased donor kidneys in six Mexican hospitals].
AB  - OBJECTIVE: To ascertain medical criteria and their priority in the allocation of
      deceased patient kidneys in pediatrics among members of Internal Transplant
      Committees of six hospitals. To assess if, by using the Delphi method, it is
      possible to reach consensus to reduce heterogeneity of criteria in the allocation
      of renal transplant organs among physicians ascribed to Nephrology and Surgery
      services in six hospital centers in Mexico. METHODOLOGY: A study was carried out
      by the Delphi method of independent experts panel, with three stages and two
      rounds. The method makes possible iteration and controlled feedback from experts
      to identify behaviors and trends with the synergy of the debate in a group. Kappa
      index was applied to assess results agreement. RESULTS: Results of first round
      show the criteria heterogeneity for the allocation of cadaveric origin organs
      within each hospital, and among hospitals compared to each other. With the
      results of the second round, consensus increased in four hospitals for the
      selection of both first and second recipient. Kappa coefficient shows the
      reliability of results. CONCLUSION: Our Country needs a point-score system to
      allocate deceased donor organs, ideally including HLA matching. Expecting that
      the Internal Transplant Committees throughout the Mexican territory may have
      available a useful tool as this, the Delphi method makes it possible to reach
      consensus in this task, in order to minimize subjectivity in the staff involved
      in the decision-making process.

PMID- 21090847
TI  - [Justice challenges of pharmaceutical industry global research].
AB  - International research projects sponsored by the pharmaceutical industry are a
      recent modality of biomedical research, which is driven by interests that are not
      only scientific, but also commercial. This combination of interests is one of the
      natural consequences of globalization, which has brought unquestionable benefits
      for the world, but has also created a wider gap between the wealthy and the poor.
      Given that globalization has been led by the the world's leading economies, the
      level of injustice in the world has increased, often to the favor of the already
      wealthy. Globalization has a well-established dynamics, whose main characteristic
      is domain over the following: technological innovation, the organization of the
      production of goods and services, human needs, and consumption. International
      biomedical research fits well in this dynamics, and the result is often a poor
      distribution of benefits, added to a loss of scientific integrity for the sake of
      commercial interests. This phenomenon raises many ethical questions and it
      demands a reflection from different bioethical points of view, particularly an
      economic ethics and a global justice.

PMID- 21090848
TI  - Local response dispersion method. II. Generalized multicenter interactions.
AB  - Recently introduced local response dispersion method [T. Sato and H. Nakai, J.
      Chem. Phys. 131, 224104 (2009)], which is a first-principles alternative to
      empirical dispersion corrections in density functional theory, is implemented
      with generalized multicenter interactions involving both atomic and atomic pair
      polarizabilities. The generalization improves the asymptote of intermolecular
      interactions, reducing the mean absolute percentage error from about 30% to 6% in
      the molecular C(6) coefficients of more than 1000 dimers, compared to
      experimental values. The method is also applied to calculations of potential
      energy curves of molecules in the S22 database [P. Jurecka et al., Phys. Chem.
      Chem. Phys. 8, 1985 (2006)]. The calculated potential energy curves are in a good
      agreement with reliable benchmarks recently published by Molnar et al. [J. Chem.
      Phys. 131, 065102 (2009)]. These improvements are achieved at the price of
      increasing complexity in the implementation, but without losing the computational
      efficiency of the previous two-center (atom-atom) formulation. A set of different
      truncations of two-center and three- or four-center interactions is shown to be
      optimal in the cost-performance balance.

PMID- 21090849
TI  - Monte Carlo cluster algorithm for fluid phase transitions in highly size
      asymmetrical binary mixtures.
AB  - Highly size-asymmetrical fluid mixtures arise in a variety of physical contexts,
      notably in suspensions of colloidal particles to which much smaller particles
      have been added in the form of polymers or nanoparticles. Conventional schemes
      for simulating models of such systems are hamstrung by the difficulty of relaxing
      the large species in the presence of the small one. Here we describe how the
      rejection-free geometrical cluster algorithm of Liu and Luijten [J. Liu and E.
      Luijten, Phys. Rev. Lett. 92, 035504 (2004)] can be embedded within a restricted
      Gibbs ensemble to facilitate efficient and accurate studies of fluid phase
      behavior of highly size-asymmetrical mixtures. After providing a detailed
      description of the algorithm, we summarize the bespoke analysis techniques of
      [Ashton et al., J. Chem. Phys. 132, 074111 (2010)] that permit accurate estimates
      of coexisting densities and critical-point parameters. We apply our methods to
      study the liquid-vapor phase diagram of a particular mixture of Lennard-Jones
      particles having a 10:1 size ratio. As the reservoir volume fraction of small
      particles is increased in the range of 0%-5%, the critical temperature decreases
      by approximately 50%, while the critical density drops by some 30%. These trends
      imply that in our system, adding small particles decreases the net attraction
      between large particles, a situation that contrasts with hard-sphere mixtures
      where an attractive depletion force occurs.

PMID- 21090850
TI  - Centroid molecular dynamics: comparison with exact results for model systems.
AB  - The relation between the accuracy of centroid molecular dynamics correlation
      functions, and the geometry of the centroid potential is investigated. It is
      shown that, depending on the temperature, there exist several regimes, and in
      each of them certain features of the exact Kubo correlation functions are
      reproduced. The change of regimes is related to the emergence of barriers in the
      centroid potential. In order to clarify how the above described picture of
      regimes is modified in real systems when dissipation is important, a methodology
      is developed to test the accuracy of centroid correlation functions for the model
      of a particle coupled to a harmonic heat bath. A modification of the centroid
      molecular dynamics method to include the influence of the heat bath is
      introduced. Preliminary results of comparison of centroid molecular dynamics with
      the numerically exact results of filtered propagator functional method are
      presented.

PMID- 21090851
TI  - Nonadiabatic coupling vectors for excited states within time-dependent density
      functional theory in the Tamm-Dancoff approximation and beyond.
AB  - Recently, we have proposed a scheme for the calculation of nonadiabatic couplings
      and nonadiabatic coupling vectors within linear response time-dependent density
      functional theory using a set of auxiliary many-electron wavefunctions [I.
      Tavernelli, E. Tapavicza, and U. Rothlisberger, J. Chem. Phys. 130, 124107
      (2009)]. As demonstrated in a later work [I. Tavernelli, B. F. E. Curchod, and U.
      Rothlisberger, J. Chem. Phys. 131, 196101 (2009)], this approach is rigorous in
      the case of the calculation of nonadiabatic couplings between the ground state
      and any excited state. In this work, we extend this formalism to the case of
      coupling between pairs of singly excited states with the same spin multiplicity.
      After proving the correctness of our formalism using the electronic oscillator
      approach by Mukamel and co-workers [S. Tretiak and S. Mukamel, Chem. Rev.
      (Washington, D.C.) 102, 3171 (2002)], we tested the method on a model system,
      namely, protonated formaldimine, for which we computed S(1)/S(2) nonadiabatic
      coupling vectors and compared them with results from high level (MR-CISD)
      electronic structure calculations.

PMID- 21090852
TI  - Dependence of the number of hydrogen bonds per water molecule on its distance to
      a hydrophobic surface and a thereupon-based model for hydrophobic attraction.
AB  - A water molecule in the vicinity of a hydrophobic surface forms fewer hydrogen
      bonds than a bulk molecule because the surface restricts the space available for
      other water molecules necessary for its hydrogen-bonding. In this vicinity, the
      number of hydrogen bonds per water molecule depends on its distance to the
      surface. Considering the number of hydrogen bonds per bulk water molecule
      (available experimentally) as the only reference quantity, we propose an improved
      probabilistic approach to water hydrogen-bonding that allows one to obtain an
      analytic expression for this dependence. (The original version of this approach
      [Y. S. Djikaev and E. Ruckenstein, J. Chem. Phys. 130, 124713 (2009)] provides
      the number of hydrogen bonds per water molecule in the vicinity of a hydrophobic
      surface as an average over all possible locations and orientations of the
      molecule.) This function (the number of hydrogen bonds per water molecule versus
      its distance to a hydrophobic surface) can be used to develop analytic models for
      the effect of hydrogen-bonding on the hydration of hydrophobic particles and
      their solvent-mediated interaction. Presenting a model for the latter, we also
      examine the temperature effect on the solvent-mediated interaction of two
      parallel hydrophobic plates.

PMID- 21090853
TI  - Quantum computing applied to calculations of molecular energies: CH2 benchmark.
AB  - Quantum computers are appealing for their ability to solve some tasks much faster
      than their classical counterparts. It was shown in [Aspuru-Guzik et al., Science
      309, 1704 (2005)] that they, if available, would be able to perform the full
      configuration interaction (FCI) energy calculations with a polynomial scaling.
      This is in contrast to conventional computers where FCI scales exponentially. We
      have developed a code for simulation of quantum computers and implemented our
      version of the quantum FCI algorithm. We provide a detailed description of this
      algorithm and the results of the assessment of its performance on the four lowest
      lying electronic states of CH(2) molecule. This molecule was chosen as a
      benchmark, since its two lowest lying (1)A(1) states exhibit a multireference
      character at the equilibrium geometry. It has been shown that with a suitably
      chosen initial state of the quantum register, one is able to achieve the
      probability amplification regime of the iterative phase estimation algorithm even
      in this case.

PMID- 21090854
TI  - On the determination of intensities for electron photodetachment and
      photoionization spectra involving states coupled by conical intersections: total
      integral cross sections for polyatomic molecules.
AB  - The formal underpinning is derived for the computational determination of
      electron photodetachment and photoionization total integral cross sections for
      molecules in which the residual species, which can be a neutral or an ion, has
      states that are strongly coupled by conical intersections. The theory takes full
      account of the requisite antisymmetry of all the electrons and the potential
      nonorthogonality of the orbital for the scattering electron to the occupied
      molecular orbitals of the residual. The breakdown of the Born-Oppenheimer
      approximation requires significant modifications to the standard adiabatic state
      theory. The developed theory builds on ideas from theories of low-energy electron
      scattering, in which the scattered electron is described by an orbital taken as
      channel dependent, but independent of nuclear coordinates. The derived
      computational approach is based on the accurate description of the vibronic
      levels of the residual species using the nonadiabatic vibronic coupling theory of
      Koppel, Domcke, and Cederbaum. The electron scattering problem is solved using
      the complex rotation L(2) method of Han and Reinhardt. This approach has the
      advantage that both Coulomb and free electron boundary conditions can be treated
      in the same approach.

PMID- 21090855
TI  - Mesoscopic structure prediction of nanoparticle assembly and coassembly:
      theoretical foundation.
AB  - In this work, we present a theoretical framework that unifies polymer field
      theory and density functional theory in order to efficiently predict ordered
      nanostructure formation of systems having considerable complexity in terms of
      molecular structures and interactions. We validate our approach by comparing its
      predictions with previous simulation results for model systems. We illustrate the
      flexibility of our approach by applying it to hybrid systems composed of block
      copolymers and ligand coated nanoparticles. We expect that our approach will
      enable the treatment of multicomponent self-assembly with a level of molecular
      complexity that approaches experimental systems.

PMID- 21090856
TI  - Water binding sites in 2-para- and 2-ortho-fluorophenylethanol: a high-resolution
      UV experiment and ab initio calculations.
AB  - The singly hydrated complexes of the flexible prototype molecules 2-para
      fluorophenylethanol and 2-ortho-fluorophenylethanol have been investigated by
      combination of high-resolution resonance-enhanced two-photon ionization
      spectroscopy in a cold supersonic beam and quantum chemistry ab initio
      calculations. We have identified the conformational structures of the above
      complexes, which correspond to water binding to the most stable gauche monomer's
      conformers in both cases. No structural changes of the host molecules upon the
      attachment of a single water molecule have been found. For the 2-ortho
      fluorophenylethanol-water complex we have observed an additional structure with
      one of the higher-in-energy gauche conformers of the monomer. This corroborates
      the assumption that the complexation with water stabilizes the higher-energy
      conformer of the monomer, precluding it from relaxation to the lowest-energy
      geometry.

PMID- 21090857
TI  - Cold chemistry with electronically excited Ca+ Coulomb crystals.
AB  - Rate constants for chemical reactions of laser-cooled Ca(+) ions and neutral
      polar molecules (CH(3)F, CH(2)F(2), or CH(3)Cl) have been measured at low
      collision energies (<E(coll)>/k(B)=5-243 K). Low kinetic energy ensembles of
      (40)Ca(+) ions are prepared through Doppler laser cooling to form "Coulomb
      crystals" in which the ions form a latticelike arrangement in the trapping
      potential. The trapped ions react with translationally cold beams of polar
      molecules produced by a quadrupole guide velocity selector or with room
      temperature gas admitted into the vacuum chamber. Imaging of the Ca(+) ion
      fluorescence allows the progress of the reaction to be monitored. Product ions
      are sympathetically cooled into the crystal structure and are unambiguously
      identified through resonance-excitation mass spectrometry using just two trapped
      ions. Variations of the laser-cooling parameters are shown to result in different
      steady-state populations of the electronic states of (40)Ca(+) involved in the
      laser-cooling cycle, and these are modeled by solving the optical Bloch equations
      for the eight-level system. Systematic variation of the steady-state populations
      over a series of reaction experiments allows the extraction of bimolecular rate
      constants for reactions of the ground state ((2)S(1/2)) and the combined excited
      states ((2)D(3/2) and (2)P(1/2)) of (40)Ca(+). These results are analyzed in the
      context of capture theories and ab initio electronic structure calculations of
      the reaction profiles. In each case, suppression of the ground state rate
      constant is explained by the presence of a submerged or real barrier on the
      ground state potential surface. Rate constants for the excited states are
      generally found to be in line with capture theories.

PMID- 21090858
TI  - The ultraviolet photodissociation of axial and equatorial conformers of 3
      pyrroline.
AB  - Resolved sets of photoproducts arising from the photodissociation of axial and
      equatorial conformers of 3-pyrroline have been observed using H(Rydberg) atom
      photofragment translational spectroscopy following excitation in the wavelength
      range of 250-213 nm. 3-pyrroline (alternatively 2,5-dihydropyrrole) is a five
      membered partially saturated heterocycle in which the bonding around the N atom
      is pyramidal (sp(3) hybridized) and the N-H bond can lie either axial or
      equatorial to the ring. Careful analysis of total kinetic energy release data
      derived from H atom time-of-flight measurements reveals excitation of the 3
      pyrrolinyl cofragment consistent with N-H bond fission in both the axial and
      equatorial conformers. This allows determination of the energy difference between
      the ground state conformers to be 340+/-50 cm(-1) and the N-H bond strength for
      axial and equatorial conformers as 31,610+/-50 and 31,270+/-50 cm(-1),
      respectively.

PMID- 21090859
TI  - IR spectroscopy on isolated Co(n)(alcohol)m cluster anions (n=1-4, m=1-3):
      structures and spin states.
AB  - Isolated cobalt-alcohol cluster anions containing n=1-4 cobalt and m=1-3 alcohol
      molecules (alcohol=methanol, ethanol, propanol) are produced in a supersonic beam
      by using a laser ablation source. By applying IR photodissociation spectroscopy
      vibrational spectra in the OH stretching region are obtained. Several structures
      in different spin states are discussed for the (n,m) clusters. In comparison with
      density functional theory calculations applied to both the Co/alcohol clusters
      and the naked Co cluster anions, an unambiguous structural assignment is
      achieved. It turns out that structures are preferred with a maximum number of
      hydrogen bonds between the OH groups and the Co...Co units. These hydrogen bonds
      are typical for anionic species leading to an activation of the OH groups which
      is indicated by large red-shifts of the OH stretching frequencies compared to the
      naked alcohols. For each (n,m) cluster, the frequency shifts systematically with
      respect to the different alcohols, but the type of structure is identical for all
      alcohol ligands. The application of IR spectroscopy turns out to be an ideal tool
      not only as a probe for structures but also for spin states which significantly
      influence the predicted OH stretching frequencies.

PMID- 21090860
TI  - Laboratory detection of protonated SO2 in two isomeric forms.
AB  - By means of Fabry-Perot Fourier transform microwave spectroscopy, the rotational
      spectrum of protonated sulfur dioxide in two distinct isomeric forms, a cis- and
      a trans-geometry, is reported. The search for both isomers was based on
      theoretical structures obtained at the CCSD(T)/cc-pwCVQZ level of theory
      corrected for zero-point vibrational effects. At a similarly high level of
      theory, the cis-isomer is calculated to be the global minimum on the potential
      energy surface, but the trans-isomer is predicted to lie only a few kcal/mol
      higher in energy. A total of seven lines, including a- and b-type transitions,
      has been observed for both isomers, and precise rotational constants have been
      derived. Because sulfur dioxide, SO(2), is a widespread and very abundant
      astronomical species, and because it possesses a large proton affinity, HOSO(+)
      is an excellent candidate for radioastronomical detection.

PMID- 21090861
TI  - Experimental measurement of the van der Waals binding energy of X-O2 clusters
      (X=Xe, CH3I, C3H6, C6H12).
AB  - Van der Waals binding energies for the X-O(2) complexes (X=Xe, CH(3)I, C(3)H(6),
      C(6)H(12)) are determined by analysis of experimental velocity map imaging data
      for O((3)P(2)) atoms arising from UV-photodissociation of the complex [A. V.
      Baklanov et al., J. Chem. Phys. 126, 124316 (2007)]. Several dissociation
      pathways have been observed, we focus on the channel corresponding to prompt
      dissociation of X-O(2) into X+2O((3)P) fragments, which is present for complexes
      of O(2) with all partners X. Our method is based on analysis of the kinetic
      energy of all three photofragments, where the O atom kinetic energy was directly
      measured in the experiment and the kinetic energy of the X partner was calculated
      using momentum conservation, along with the measured angular anisotropy for O
      atom recoil. We exploit the fact that the clusters are all T-shaped or nearly T
      shaped, which we also confirm by ab initio calculations, along with knowledge of
      the transition dipole governing radiative absorption by the complex. The effect
      of partitioning the kinetic energy between translation along the X-O(2) and O-O
      coordinates on the angular anisotropy of the O atom recoil direction is
      discussed. Van der Waals binding energies of 110+/-20 cm(-1), 280+/-20 cm(-1),
      135+/-30 cm(-1), and 585+/-20 cm(-1) are determined for Xe-O(2), CH(3)I-O(2),
      C(3)H(6)-O(2), and C(6)H(12)-O(2) clusters, respectively.

PMID- 21090862
TI  - Molecular dynamics study of the crystallization of nitromethane from the melt.
AB  - The crystallization of nitromethane, CH(3)NO(2), from the melt on the (100),
      (010), (001), and (110) crystal surfaces at 170, 180, 190, 200, 210, and 220 K
      has been investigated using constant-volume and -temperature (NVT) molecular
      dynamics simulations with a realistic, fully flexible force field [D. C. Sorescu,
      B. M. Rice, and D. L. Thompson, J. Phys. Chem. B 104, 8406 (2000)]. The
      crystallization process and the nature of the solid-liquid interface have been
      investigated by computing the molecular orientations, density, and radial
      distribution functions as functions of time and location in the simulation cell.
      During crystallization the translational motion of the molecules ceases first,
      after which molecular rotation ceases as the molecules assume proper orientations
      in the crystal lattice. The methyl groups are hindered rotors in the liquid;
      hindrance to rotation is reduced upon crystallization. The width of the solid
      liquid interface varies between 6 and 13 A (about two to five molecular layers)
      depending on which crystal surface is exposed to the melt and which order
      parameter is used to define the interface. The maximum rate of crystallization
      varies from 0.08 molecules ns(-1) A(-2) for the (010) surface at 190 K to 0.41
      molecules ns(-1) A(-2) for the (001) surface at 220 K.

PMID- 21090863
TI  - High resolution NMR study of T1 magnetic relaxation dispersion. II. Influence of
      spin-spin couplings on the longitudinal spin relaxation dispersion in multispin
      systems.
AB  - Effects of scalar spin-spin interactions on the nuclear magnetic relaxation
      dispersion (NMRD) of coupled multispin systems were analyzed. Taking spin systems
      of increasing complexity we demonstrated pronounced influence of the
      intramolecular spin-spin couplings on the NMRD of protons. First, at low magnetic
      fields where there is strong coupling of spins the apparent relaxation times of
      the coupled spins become equal. Second, there are new features, which appear at
      the positions of the nuclear spin level anticrossings. Finally, in coupled spin
      systems there can be a coherent contribution to the relaxation kinetics present
      at low magnetic fields. All these peculiarities caused by spin-spin interactions
      are superimposed on the features in NMRD, which are conditioned by changes of the
      motional regime. Neglecting the effects of couplings may lead to
      misinterpretation of the NMRD curves and significant errors in determining the
      correlation times of molecular motion. Experimental results presented are in good
      agreement with theoretical calculations.

PMID- 21090864
TI  - Electron induced reactions in molecular nanofilms of chlorodifluoroacetic acid
      (CClF2COOH): desorption of fragment anions and formation of CO2.
AB  - Electron induced reactions in molecular nanofilms of chlorodifluoroacetic acid
      (CClF(2)COOH) are studied by electron stimulated desorption (ESD) of fragment
      anions and temperature programed thermal desorption spectroscopy (TDS). The
      fragment anions O(-), F(-), OH(-), and Cl(-) are formed from broad resonance
      features in the energy range of 4-14 eV and assigned to dissociative electron
      attachment (DEA) of molecules or dimers at or near the surface of the film,
      followed by desorption. The strong low energy DEA resonances (0-2 eV) observed in
      a previous gas phase study [J. Kopyra et al., Int. J. Mass. Spectrom. 285, 131
      (2009)] are completely suppressed in ESD. Electron irradiation at energies above
      10 eV results in the formation of CO(2), as revealed by TDS. The extended
      irradiation of a 3 ML film (25 nA, 240 min) results in a nearly completely
      transformation of the initial compound in favor of CO(2) and other by-products.

PMID- 21090865
TI  - Structure prediction and targeted synthesis: a new Na(n)N2 diazenide crystalline
      structure.
AB  - Significant progress in theoretical and computational techniques for predicting
      stable crystal structures has recently begun to stimulate targeted synthesis of
      such predicted structures. Using a global space-group optimization (GSGO)
      approach that locates ground-state structures and stable stoichiometries from
      first-principles energy functionals by objectively starting from randomly
      selected lattice vectors and random atomic positions, we predict the first alkali
      diazenide compound Na(n)N(2), manifesting homopolar N-N bonds. The previously
      predicted Na(3)N structure manifests only heteropolar Na-N bonds and has positive
      formation enthalpy. It was calculated based on local Hartree-Fock relaxation of a
      fixed-structure type (Li(3)P-type) found by searching an electrostatic point-ion
      model. Synthesis attempts of this positive DeltaH compound using activated
      nitrogen yielded another structure (anti-ReO(3)-type). The currently predicted
      (negative formation enthalpy) diazenide Na(2)N(2) completes the series of
      previously known BaN(2) and SrN(2) diazenides where the metal sublattice
      transfers charge into the empty N(2) Pi(g) orbital. This points to a new class of
      alkali nitrides with fundamentally different bonding, i.e., homopolar rather than
      heteropolar bonds and, at the same time, illustrates some of the crucial
      subtleties and pitfalls involved in structure predictions versus planned
      synthesis. Attempts at synthesis of the stable Na(2)N(2) predicted here will be
      interesting.

PMID- 21090866
TI  - Studies on the translational and rotational motions of ionic liquids composed of
      N-methyl-N-propyl-pyrrolidinium (P13) cation and
      bis(trifluoromethanesulfonyl)amide and bis(fluorosulfonyl)amide anions and their
      binary systems including lithium salts.
AB  - Room-temperature ionic liquids (RTIL, IL) are stable liquids composed of anions
      and cations. N-methyl-N-propyl-pyrrolidinium (P(13), Py(13), PYR(13), or mppy) is
      an important cation and produces stable ILs with various anions. In this study
      two amide-type anions, bis(trifluoromethanesulfonyl)amide [N(SO(2)CF(3))(2),
      TFSA, TFSI, NTf(2), or Tf(2)N] and bis(fluorosulfonyl)amide [N(SO(2)F)(2), FSA,
      or FSI], were investigated. In addition to P(13)-TFSA and P(13)-FSA, lithium salt
      doped samples were prepared (P(13)-TFSA-Li and P(13)-FSA-Li). The individual ion
      diffusion coefficients (D) and spin-lattice relaxation times (T(1)) were measured
      by (1)H, (19)F, and (7)Li NMR. At the same time, the ionic conductivity (sigma),
      viscosity (eta), and density (rho) were measured over a wide temperature range.
      The van der Waals volumes of P(13), TFSA, FSA, Li(TFSA)(2), and Li(FSA)(3) were
      estimated by molecular orbital calculations. The experimental values obtained in
      this study were analyzed by the classical Stokes-Einstein, Nernst-Einstein (NE),
      and Stokes-Einstein-Debye equations and Walden plots were also made for the neat
      and binary ILs to clarify physical and mobile properties of individual ions. From
      the temperature-dependent velocity correlation coefficients for neat P(13)-TFSA
      and P(13)-FSA, the NE parameter 1-xi was evaluated. The ionicity (electrochemical
      molar conductivity divided by the NE conductivity from NMR) and the 1-xi had
      exactly the same values. The rotational and translational motions of P(13) and
      jump of a lithium ion are also discussed.

PMID- 21090867
TI  - Thermoelectric properties of Yb(x)Eu(1-x)Cd2Sb2.
AB  - The thermoelectric performance of EuCd(2)Sb(2) and YbCd(2)Sb(2) was improved by
      mixed cation occupation. The composition, structure, and thermoelectric
      properties of Yb(x)Eu(1-x)Cd(2)Sb(2) (x=0, 0.5, 0.75, and 1) have been
      investigated. Polycrystalline samples are prepared by direct reaction of the
      elements. Thermoelectric properties were investigated after densification of the
      materials by spark plasma sintering. Yb(x)Eu(1-x)Cd(2)Sb(2) crystallizes in the
      P3m1 space group. The lattice parameters increase with the europium content.
      These materials show low electrical resistivity, high Seebeck coefficient, and
      low thermal conductivity together with high carrier concentration and high
      carrier mobility. ZT values of 0.88 and 0.97 are obtained for
      Yb(0.5)Eu(0.5)Cd(2)Sb(2) and Yb(0.75)Eu(0.25)Cd(2)Sb(2) at 650 K, respectively.

PMID- 21090868
TI  - Theoretical analysis of initial adsorption of high-kappa metal oxides on
      In(x)Ga(1-x)As(0 0 1)-(4*2) surfaces.
AB  - Ordered, low coverage to monolayer, high-kappa oxide adsorption on group III rich
      InAs(0 0 1)-(4*2) and In(0.53)Ga(0.47)As(0 0 1)-(4*2) was modeled via density
      functional theory (DFT). Initial adsorption of HfO(2) and ZrO(2) was found to
      remove dangling bonds on the clean surface. At full monolayer coverage, the oxide
      semiconductor bonds restore the substrate surface atoms to a more bulklike
      bonding structure via covalent bonding, with the potential for an unpinned
      interface. DFT models of ordered HfO(2)/In(0.53)Ga(0.47)As(0 0 1)-(4*2) show it
      fully unpins the Fermi level.

PMID- 21090869
TI  - Formation of undulated lamellar structure from ABC block terpolymer blends with
      different chain lengths.
AB  - The effect of molecular weight distribution of ABC linear terpolymers on the
      formation of periodic structures was investigated. Three poly(isoprene-b-styrene
      b-2-vinylpridine) triblockterpolymers with molecular weights of 26k, 96k, and
      150k were blended variously. Three-phase, four-layer lamellar structures were
      observed when polydispersity index (PDI) was low, but it has been found that
      simple lamellar structure with flat surface transforms into an undulated lamellar
      one, where two interfaces, i.e., I/S and S/P, are both undulated, and they are
      synchronizing each other if PDI exceeds the critical value. This new structure
      could be formed due to the periodic and "weak" localization of three chains along
      the domain interfaces, which produces periodic surfaces with nonconstant mean
      curvatures. With further increase of PDI, the blend macroscopically phase
      separated into different microphase-separated structures.

PMID- 21090870
TI  - Linear viscoelastic properties of transient networks formed by associating
      polymers with multiple stickers.
AB  - We have developed a single-chain theory that describes dynamics of associating
      polymer chains carrying multiple associative groups (or stickers) in the
      transient network formed by themselves and studied linear viscoelastic properties
      of this network. It is shown that if the average number N of stickers associated
      with the network junction per chain is large, the terminal relaxation time tau(A)
      that is proportional to tau(X)N(2) appears. The time tau(X) is the interval
      during which an associated sticker goes back to its equilibrium position by one
      or more dissociation steps. In this lower frequency regime omega<1/tau(X), the
      moduli are well described in terms of the Rouse model with the longest relaxation
      time tau(A). The large value of N is realized for chains carrying many stickers
      whose rate of association with the network junction is much larger than the
      dissociation rate. This associative Rouse behavior stems from the
      association/dissociation processes of stickers and is different from the ordinary
      Rouse behavior in the higher frequency regime, which is originated from the
      thermal segmental motion between stickers. If N is not large, the dynamic shear
      moduli are well described in terms of the Maxwell model characterized by a single
      relaxation time tau(X) in the moderate and lower frequency regimes. Thus, the
      transition occurs in the viscoelastic relaxation behavior from the Maxwell-type
      to the Rouse-type in omega<1/tau(X) as N increases. All these results are
      obtained under the affine deformation assumption for junction points. We also
      studied the effect of the junction fluctuations from the affine motion on the
      plateau modulus by introducing the virtual spring for bound stickers. It is shown
      that the plateau modulus is not affected by the junction fluctuations.

PMID- 21090871
TI  - Stochastic theory of large-scale enzyme-reaction networks: finite copy number
      corrections to rate equation models.
AB  - Chemical reactions inside cells occur in compartment volumes in the range of atto
      to femtoliters. Physiological concentrations realized in such small volumes
      imply low copy numbers of interacting molecules with the consequence of
      considerable fluctuations in the concentrations. In contrast, rate equation
      models are based on the implicit assumption of infinitely large numbers of
      interacting molecules, or equivalently, that reactions occur in infinite volumes
      at constant macroscopic concentrations. In this article we compute the finite
      volume corrections (or equivalently the finite copy number corrections) to the
      solutions of the rate equations for chemical reaction networks composed of
      arbitrarily large numbers of enzyme-catalyzed reactions which are confined inside
      a small subcellular compartment. This is achieved by applying a mesoscopic
      version of the quasisteady-state assumption to the exact Fokker-Planck equation
      associated with the Poisson representation of the chemical master equation. The
      procedure yields impressively simple and compact expressions for the finite
      volume corrections. We prove that the predictions of the rate equations will
      always underestimate the actual steady-state substrate concentrations for an
      enzyme-reaction network confined in a small volume. In particular we show that
      the finite-volume corrections increase with decreasing subcellular volume,
      decreasing Michaelis-Menten constants, and increasing enzyme saturation. The
      magnitude of the corrections depends sensitively on the topology of the network.
      The predictions of the theory are shown to be in excellent agreement with
      stochastic simulations for two types of networks typically associated with
      protein methylation and metabolism.

PMID- 21090873
TI  - Etiology of obsessions and compulsions: a behavioral-genetic analysis.
AB  - It is unknown whether various types of obsessive-compulsive (OC) symptoms have a
      common genetic or environmental etiology. For example, it is unknown whether
      hoarding is etiologically associated with prototypic OC symptoms, such as
      washing, checking, and obsessing. Also unknown is whether particular OC-related
      symptoms are etiologically linked to the general tendency to experience emotional
      distress (negative emotionality). To investigate these and other issues, a
      community sample of 307 pairs of monozygotic and dizygotic adult twins provided
      scores on 6 OC-related symptoms (obsessing, neutralizing, checking, washing,
      ordering, and hoarding) and 2 markers of negative emotionality (trait anxiety and
      affective lability). Genetic factors accounted for 40%-56% of variance in the 8
      phenotypic scores (M = 49% of variance for OC-related symptoms). Remaining
      variance was due to nonshared (person-specific) environment. More detailed
      analyses revealed a complex etiologic architecture, where OC-related symptoms
      arise from a mix of common and symptom-specific genetic and environmental
      factors. A general genetic factor was identified, which influenced all symptoms
      and negative emotionality. An environmental factor was identified that influenced
      all symptoms but did not influence negative emotionality. Each of the 6 types of
      symptoms was also shaped by its own set of symptom-specific genetic and
      environmental factors. The importance of genetic factors did not vary as a
      function of age or sex, and the architecture of general and specific etiologic
      factors was replicated for participants having relatively more severe OC
      symptoms. Gene-environment interactions were identified. Implications for an
      etiology-based classification system are discussed.

PMID- 21090874
TI  - Building an evidence base for DSM-5 conceptualizations of oppositional defiant
      disorder and conduct disorder: introduction to the special section.
AB  - The DSM-5 ADHD and Disruptive Behavior Disorders Work Group recently outlined a
      research agenda designed to support possible revisions to the diagnostic criteria
      for oppositional defiant disorder (ODD) and conduct disorder (CD). Some of the
      areas in need of further investigation include (a) examining the clinical utility
      of the current diagnostic system in girls, (b) further clarifying the
      developmental progression from ODD to CD, (c) determining whether facets of ODD
      symptoms can help explain heterotypic continuity and enhance predictive validity,
      (d) evaluating the clinical utility of a new subtyping scheme for CD on the basis
      of the presence of callous-unemotional traits, and (e) comparing the clinical
      utility of dimensional versus categorical conceptualizations of ODD and CD. This
      special section was organized in an attempt to provide data on these issues using
      a diverse array of longitudinal data sets consisting of both epidemiological and
      clinic-based samples that collectively cover a large developmental span ranging
      from childhood through early adulthood.

PMID- 21090875
TI  - ODD dimensions, ADHD, and callous-unemotional traits as predictors of treatment
      response in children with disruptive behavior disorders.
AB  - To answer several questions pertinent to DSM-V, the authors examined the
      predictive validity of pretreatment oppositional defiant disorder (ODD)
      dimensions, attention-deficit/hyperactivity disorder (ADHD), and callous
      unemotional (CU) traits in relation to several treatment outcomes in 177 children
      diagnosed with ODD or conduct disorder (CD). Multiple informants completed
      diagnostic interviews and rating scales at 6 assessment points (pretreatment to 3
      year follow-up) to document emotional and behavioral outcomes. After controlling
      for pretreatment CD, the ODD dimension of hurtfulness was related to treatment
      resistant CD, delinquent behaviors, and externalizing problems. In contrast, the
      ODD dimension tapping irritability was associated with treatment-resistant ODD,
      internalizing problems, and global functional impairment following treatment.
      Whereas pretreatment ADHD was associated with posttreatment ODD and social
      problems, it was unrelated to posttreatment CD symptoms and diagnosis. Contrary
      to predictions, CU traits were unrelated to any posttreatment outcomes after
      controlling for other covariates. These findings remained after controlling for
      measures of pretreatment global functional impairment.

PMID- 21090876
TI  - Developmental pathways in oppositional defiant disorder and conduct disorder.
AB  - The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV;
      American Psychiatric Association, 1994) specifies a developmental relationship
      between oppositional defiant disorder (ODD) and conduct disorder (CD). Evidence
      for this link is mixed, however, and recent studies suggest that different
      symptom dimensions in ODD may have different outcomes. The authors examined links
      between ODD, CD, and their young adult outcomes in the Great Smoky Mountains
      Study (E. J. Costello et al., 1996), a longitudinal data set with over 8,000
      observations of 1,420 individuals (56% male) covering ages 9-21 years. ODD was a
      significant predictor of later CD in boys but not in girls after control for
      comorbid CD and subthreshold CD symptomatology. Transitions between ODD and CD
      were less common than anticipated, however, particularly during adolescence. The
      authors examined characteristics and outcomes of children with pure ODD, pure CD,
      and combined CD/ODD. Alongside many similarities in childhood and adolescent
      correlates, key differences were also identified: CD largely predicted behavioral
      outcomes, whereas ODD showed stronger prediction to emotional disorders in early
      adult life. Factor analysis identified irritable and headstrong dimensions in ODD
      symptoms that showed differential prediction to later behavioral and emotional
      disorders. Overall, the results underscore the utility of retaining separate ODD
      and CD diagnoses in DSM-V.

PMID- 21090877
TI  - A meta-analytic investigation of the structure of posttraumatic stress disorder
      symptoms.
AB  - Converging lines of evidence have called into question the validity of
      conceptualizations of posttraumatic stress disorder (PTSD) based on the
      Diagnostic and Statistical Manual of Mental Disorders (DSM; American Psychiatric
      Association, 2000) and suggested alternative structural models of PTSD
      symptomatology. We conducted a meta-analysis of 40 PTSD studies (N = 14,827
      participants across studies) that used a DSM-based measure to assess PTSD
      severity. We aggregated correlation matrices across studies and then applied
      confirmatory factor analysis to the aggregated matrices to test the fit of
      competing models of PTSD symptomatology that have gained support in the
      literature. Results indicated that both prominent 4-factor models of PTSD
      symptomatology yielded good model fit across subsamples of studies; however, the
      model comprising Intrusions, Avoidance, Hyperarousal, and Dysphoria factors
      appeared to fit better across studies. Results also indicated that the best
      fitting models were not moderated by measure or sample type. Results are
      discussed in the context of structural models of PTSD and implications for the
      diagnostic nosology.

PMID- 21090878
TI  - Conceptual and perceptual priming and dissociation in chronic posttraumatic
      stress disorder.
AB  - Cognitive models of posttraumatic stress disorder (PTSD) assert that memory
      processes play a significant role in PTSD (see e.g., Ehlers & Clark, 2000).
      Intrusive reexperiencing in PTSD has been linked to perceptual processing of
      trauma-related material with a corresponding hypothesized lack of conceptual
      processing. In an experimental study that included clinical participants with and
      without PTSD (N = 50), perceptual priming and conceptual priming for trauma
      related, general threat, and neutral words were investigated in a population with
      chronic trauma-induced complaints as a result of the Troubles in Northern
      Ireland. The study used a new version of the word-stem completion task (Michael,
      Ehlers, & Halligan, 2005) and a word-cue association task. It also assessed the
      role of dissociation in threat processing. Further evidence of enhanced
      perceptual priming in PTSD for trauma stimuli was found, along with evidence of
      lack of conceptual priming for such stimuli. Furthermore, this pattern of priming
      for trauma-related words was associated with PTSD severity, and state
      dissociation and PTSD group made significant contributions to predicting
      perceptual priming for trauma words. The findings shed light on the importance of
      state dissociation in trauma-related information processing and posttraumatic
      symptoms.

PMID- 21090879
TI  - Developmental relations between depressive symptoms, minor hassles, and major
      events from adolescence through age 30 years.
AB  - Stress generation and stress exposure models of the relations among depressive
      symptoms, minor hassles, and major event stress were investigated among 815
      community-dwelling participants. Autoregressive latent trajectory models were
      constructed to examine latent growth patterns from ages 15 years to 30 years and
      to test 1-year lagged, reciprocal paths between depressive symptoms and stress
      constructs. Results indicated significant cross-sectional and longitudinal
      associations between depressive symptoms and both stress constructs at the latent
      level. At the manifest level, lagged paths from hassles at 1 year to depressive
      symptoms at the next year were significant between ages 17 years and 24 years.
      Significant cross-sectional paths between major events and depressive symptoms
      were found between ages 24 years and 28 years, and modest support was found for
      lagged paths from depressive symptoms to major events 1 year later. Findings
      generally suggest a high degree of covariation in depressive symptoms and stress
      concurrently and over time. One-year lagged predictive effects net of the
      associations between individuals' latent trajectories appear to be weak,
      constrained to specific time periods, and most consistent with a stress exposure
      effect of hassles on depressive symptoms.

PMID- 21090880
TI  - Tightly linked systems: reciprocal relations between maternal depressive symptoms
      and maternal reports of adolescent externalizing behavior.
AB  - The frequently observed link between maternal depressive symptoms and heightened
      maternal reporting of adolescent externalizing behavior was examined from an
      integrative, systems perspective using a community sample of 180 adolescents,
      their mothers, fathers, and close peers, assessed twice over a 3-year period.
      Consistent with this perspective, the maternal depression-adolescent
      externalizing link was found to reflect not simply maternal reporting biases, but
      heightened maternal sensitivity to independently observable teen misbehavior as
      well as long-term, predictive links between maternal symptoms and teen behavior.
      Maternal depressive symptoms predicted relative increases over time in teen
      externalizing behavior. Child effects were also found, however, in which teen
      externalizing behavior predicted future relative increases in maternal depressive
      symptoms. Findings are interpreted as revealing a tightly linked behavioral
      affective system in families with mothers experiencing depressive symptoms and
      teens engaged in externalizing behavior and further suggest that research on
      depressive symptoms in women with adolescent offspring should now consider
      offspring externalizing behaviors as a significant risk factor.

PMID- 21090881
TI  - Aberrant neural processing of moral violations in criminal psychopaths.
AB  - A defining characteristic of psychopathy is the willingness to intentionally
      commit moral transgressions against others without guilt or remorse. Despite this
      "moral insensitivity," the behavioral and neural correlates of moral decision
      making in psychopathy have not been well studied. To address this issue, the
      authors used functional magnetic resonance imaging (fMRI) to record hemodynamic
      activity in 72 incarcerated male adults, stratified into psychopathic (n = 16)
      and nonpsychopathic (n = 16) groups based on scores from the Hare Psychopathy
      Checklist-Revised (R. D. Hare, 2003), while they made decisions regarding the
      severity of moral violations of pictures that did or did not depict moral
      situations. Consistent with hypotheses, an analysis of brain activity during the
      evaluation of pictures depicting moral violations in psychopaths versus
      nonpsychopaths showed atypical activity in several regions involved in moral
      decision-making. This included reduced moral/nonmoral picture distinctions in the
      ventromedial prefrontal cortex and anterior temporal cortex in psychopaths
      relative to nonpsychopaths. In a separate analysis, the association between
      severity of moral violation ratings and brain activity across participants was
      compared in psychopaths versus nonpsychopaths. Results revealed a positive
      association between amygdala activity and severity ratings that was greater in
      nonpsychopaths than psychopaths, and a negative association between posterior
      temporal activity and severity ratings that was greater in psychopaths than
      nonpsychopaths. These results reveal potential neural underpinnings of moral
      insensitivity in psychopathy and are discussed with reference to neurobiological
      models of morality and psychopathy.

PMID- 21090883
TI  - Expressed emotion and sociocultural moderation in the course of schizophrenia.
AB  - This study examined whether the sociocultural context moderates the relationship
      between families' expressed emotion (EE) and clinical outcomes in schizophrenia.
      In a sample of 60 Mexican American caregivers and their ill relatives, we first
      assessed whether EE and its indices (criticism, emotional overinvolvement [EOI],
      and warmth) related to relapse. Second, we extended the analysis of EE and its
      indices to a longitudinal assessment of symptomatology. Last, we tested whether
      bidimensional acculturation moderated the relationship between EE (and its
      indices) and both relapse and symptom trajectory over time. Results indicated
      that EOI was associated with increased relapse and that criticism was associated
      with increased symptomatology. Additionally, as patients' Mexican enculturation
      (Spanish language and media involvement) decreased, EE was increasingly related
      to relapse. For symptomatology, as patients' U.S. acculturation (English language
      and media involvement) increased, EE was associated with increased symptoms
      longitudinally. Our results replicate and extend past research on how culture
      might shape the way family factors relate to the course of schizophrenia.

PMID- 21090884
TI  - Toward a theory of discontinuous career transition: investigating career
      transitions necessitated by traumatic life events.
AB  - Career researchers have focused on the mechanisms related to career progression.
      Although less studied, situations in which traumatic life events necessitate a
      discontinuous career transition are becoming increasingly prevalent. Employing a
      multiple case study method, we offer a deeper understanding of such transitions
      by studying an extreme case: soldiers and Marines disabled by wartime combat. Our
      study highlights obstacles to future employment that are counterintuitive and
      stem from the discontinuous and traumatic nature of job loss. Effective
      management of this type of transitioning appears to stem from efforts positioned
      to formulate a coherent narrative of the traumatic experience and thus to
      reconstruct foundational assumptions about the world, humanity, and self. These
      foundational assumptions form the basis for enacting future-orientated career
      strategies, such that progress toward establishing a new career path is greatest
      for those who can orientate themselves away from the past (trauma), away from the
      present (obstacles to a new career), and toward an envisioned future career
      positioned to confer meaning and purpose through work.

PMID- 21090886
TI  - The importance of the peritraumatic experience in defining traumatic stress.
AB  - In the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.,
      DSM-IV-TR; American Psychiatric Association, 2000), posttraumatic stress disorder
      (PTSD) Criterion A2 stipulates that an individual must experience intense fear,
      helplessness, or horror during an event that threatened the life or physical
      integrity of oneself or others to be eligible for the PTSD diagnosis. In
      considering this criterion, we describe its origins, review studies that have
      examined its predictive validity, and reflect on the intended purpose of the
      criterion and how it complements the mission of the DSM. We then assert that the
      predictive validity of Criterion A2 may not be an appropriate metric for
      evaluating its worth. We also note that the current Criterion A2 may not fully
      capture all the salient aspects of the traumatic stress response. To support this
      claim, we review empirical research showing that individuals adapt to extreme
      environmental events by responding in a complex and coordinated manner. This
      complex response set involves an individual's appraisal regarding the degree to
      which the event taxes his or her resources, as well as a range of other
      cognitions (e.g., dissociation), felt emotions (e.g., fear), physiological
      reactions (e.g., heart rate increase), and behaviors (e.g., tonic immobility). We
      provide evidence that these response components may be associated with the
      subsequent development of PTSD. We then describe the challenges associated with
      accurately assessing an individual's traumatic stress response. We conclude with
      a discussion of the need to consider the individual's immediate response when
      defining a traumatic stressor.

PMID- 21090887
TI  - Do procedures for verbal reporting of thinking have to be reactive? A meta
      analysis and recommendations for best reporting methods.
AB  - Since its establishment, psychology has struggled to find valid methods for
      studying thoughts and subjective experiences. Thirty years ago, Ericsson and
      Simon (1980) proposed that participants can give concurrent verbal expression to
      their thoughts (think aloud) while completing tasks without changing objectively
      measurable performance (accuracy). In contrast, directed requests for concurrent
      verbal reports, such as explanations or directions to describe particular kinds
      of information, were predicted to change thought processes as a consequence of
      the need to generate this information, thus altering performance. By comparing
      performance of concurrent verbal reporting conditions with their matching silent
      control condition, Ericsson and Simon found several studies demonstrating that
      directed verbalization was associated with changes in performance. In contrast,
      the lack of effects of thinking aloud was merely suggested by a handful of
      experimental studies. In this article, Ericsson and Simon's model is tested by a
      meta-analysis of 94 studies comparing performance while giving concurrent
      verbalizations to a matching condition without verbalization. Findings based on
      nearly 3,500 participants show that the "think-aloud" effect size is
      indistinguishable from zero (r = -.03) and that this procedure remains
      nonreactive even after statistically controlling additional factors such as task
      type (primarily visual or nonvisual). In contrast, procedures that entail
      describing or explaining thoughts and actions are significantly reactive, leading
      to higher performance than silent control conditions. All verbal reporting
      procedures tend to increase times to complete tasks. These results suggest that
      think-aloud should be distinguished from other methods in future studies.
      Theoretical and practical implications are discussed.

PMID- 21090888
TI  - Visual kin recognition in nonhuman primates: (Pan troglodytes and Macaca
      mulatta): inbreeding avoidance or male distinctiveness?
AB  - Faces provide important information about identity, age, and even kinship. A
      previous study in chimpanzees reported greater similarity between the faces of
      mothers and sons compared with mothers and daughters, or unrelated individuals.
      This was interpreted as an inbreeding avoidance mechanism where females, the
      dispersing gender, should avoid mating with any male that resembles their mother.
      Alternatively, male faces may be more distinctive than female faces, biasing
      attention toward males. To test these hypotheses, chimpanzees and rhesus monkeys
      matched conspecifics' faces of unfamiliar mothers and fathers with their sons and
      daughters. Results showed no evidence of male distinctiveness, rather a cross
      gender effect was found: chimpanzees were better matching moms with sons and
      fathers with daughters. Rhesus monkeys, however, showed an overwhelming bias
      toward male-distinctiveness. They were faster to learn male faces, performed
      better on father-offspring and parent-son trials, and were best matching fathers
      with sons. This suggests that for the rhesus monkey, inbreeding avoidance
      involves something other than facial phenotypic matching but that among
      chimpanzees, the visual recognition of facial similarities may play an important
      role.

PMID- 21090889
TI  - Orangutans (Pongo spp.) may prefer tools with rigid properties to flimsy tools.
AB  - Preference for tools with either rigid or flexible properties was explored in
      orangutans (Pongo spp.) through an extension of D. J. Povinelli, J. E. Reaux, and
      L. A. Theall's (2000) flimsy-tool problem. Three captive orangutans were
      presented with three unfamiliar pairs of tools to solve a novel problem. Although
      each orangutan has spontaneously used tools in the past, the tools presented in
      this study were novel to the apes. Each pair of tools contained one tool with
      rigid properties (functional) and one tool with flimsy properties
      (nonfunctional). Solving the problem required selection of a rigid tool to
      retrieve a food reward. The functional tool was selected in nearly all trials.
      Moreover, two of the orangutans demonstrated this within the first test trials
      with each of the three tool types. Although further research is required to test
      this statistically, it suggests either a preexisting preference for rigid tools
      or comprehension of the relevant features required in a tool to solve the task.
      The results of this study demonstrate that orangutans can recognize, or learn to
      recognize, relevant tool properties and can choose an appropriate tool to solve a
      problem.

PMID- 21090890
TI  - Use of binaural cues for sound localization in two species of Phyllostomidae: the
      Greater spear-nosed bat (Phyllostomus hastatus) and the Short-tailed fruit bat
      (Carollia perspicillata).
AB  - Unlike humans, not all mammals use both of the binaural cues for sound
      localization. Whether an animal uses these cues can be determined by testing its
      ability to localize pure tones; specifically, low frequencies are localized using
      time-difference cues, and high frequencies are localized using intensity
      difference cues. We determined the ability to use binaural cues in 2 New World
      bats, Phyllostomus hastatus, large omnivores, and Carollia perspicillata, small
      frugivores, by testing their tone-localization ability using a conditioned
      avoidance procedure. Both species easily localized high-frequency tones,
      indicating that they could use the interaural intensity-difference cue. However,
      neither species was able to use the phase-difference cue to localize either low
      frequency pure tones or amplitude-modulated tones (which provided an envelope for
      additional time analysis). We now know of 3 bat species that cannot use binaural
      time cues and 2 that can. Further exploration of localization in bats may provide
      insight into the neural analysis of time cues in species that do not hear low
      frequencies.

PMID- 21090891
TI  - Bitter avoidance in guinea pigs (Cavia porcellus) and mice (Mus musculus and
      Peromyscus leucopus).
AB  - Rejection of bitter substances is common in many species and may function to
      protect an animal from ingestion of bitter-tasting toxins. Since many plants are
      bitter, it has been proposed that high tolerance for bitterness would be adaptive
      for herbivores. Earlier studies conducted on herbivorous guinea pigs (Cavia
      porcellus) have been used to support this proposal. We tested guinea pigs with
      bitter plant secondary metabolites (salicin, caffeine, quinine hydrochloride) and
      bitter protein hydrolysates (two types of hydrolyzed casein, hydrolyzed soy) in a
      series of two-choice preference tests. For comparison, we tested two
      nonherbivorous mouse species (Mus musculus and Peromyscus leucopus). Guinea pigs
      did show weaker avoidance of quinine hydrochloride than did the mice, confirming
      predictions generated from earlier work. However, guinea pigs had similar
      responses to caffeine as did Peromyscus. Both of these species showed weaker
      avoidance responses than Mus to 10 mM caffeine. For salicin, guinea pigs were the
      only species to avoid it at 10 mM and their preference scores at this
      concentration were significantly lower than for the two mice species. Guinea pigs
      avoided all of the protein hydrolysates more strongly than the other species.
      Responses to the protein hydrolysates did not reflect the patterns observed with
      the simple bitter compounds, suggesting that other properties of these complex
      stimuli may be responsible for guinea pig avoidance of them. Our results suggest
      caution in accepting, without further empirical support, the premise that guinea
      pigs (and herbivores in general) have a generalized reduced bitter sensitivity.

PMID- 21090892
TI  - Health Psychology: adieu and renew.

PMID- 21090893
TI  - Tailored versus generic interventions for skin cancer risk reduction for family
      members of melanoma patients.
AB  - BACKGROUND: Improving strategies for risk reduction among family members of
      patients with melanoma may reduce their risk for melanoma. OBJECTIVE: To evaluate
      the effects of two behavioral interventions designed to improve the frequency of
      total cutaneous skin examination by a health provider (TCE), skin self
      examination (SSE), and sun protection among first degree relatives of patients
      with melanoma; and to evaluate whether increased intentions, increased benefits,
      decreased barriers, and improved sunscreen self-efficacy mediated the effects of
      the tailored intervention, as compared with the generic intervention on TCE, SSE,
      or sun protection. METHODS: Four hundred forty-three family members (56 parents,
      248 siblings, 239 children) who were nonadherent with these practices were
      randomly assigned to either a generic (N = 218) or a tailored intervention (N =
      225) which included 3 print mailings and 1 telephone session. Participants
      completed measures of TCE, SSE, and sun protections at baseline, 6 months, and 1
      year, and measures of intentions, benefits, barriers, and self-efficacy at
      baseline and 6 months. RESULTS: Those enrolled in the tailored intervention had
      almost a twofold increased probability of having a TCE ( p < .0001). Treatment
      effects in favor of the tailored intervention were also noted for sun protection
      habits ( p < .02). Increases in TCE intentions mediated the tailored
      intervention's effects on TCE. Increases in sun protection intentions mediated
      effects of the tailored intervention's effect on sun protection. CONCLUSIONS:
      Tailored interventions may improve risk reduction practices among family members
      of patients with melanoma.

PMID- 21090894
TI  - "I just signed": Factors influencing decision-making for school-based HPV
      vaccination of adolescent girls.
AB  - OBJECTIVES: Australia was one of the first countries to implement a nationwide
      program providing HPV vaccination to girls at school. To date, there are no
      published studies describing decision-making processes and behavior
      postimplementation of HPV vaccination of adolescents participating in a school
      based program. DESIGN: A purposive sample of nine schools was selected to reflect
      a range of vaccination coverage and school types. Semistructured focus groups
      with girls and interviews with parents, teachers, and immunization nurses (n =
      185) were conducted until saturation was reached. Transcripts were analyzed
      inductively and emergent themes were subject to constant comparison. MAIN OUTCOME
      MEASURES: Explanatory model of decision-making in HPV vaccination. RESULTS: An
      explanatory model of decision-making and behavior was constructed from the data.
      Five decision-making states emerged across a continuum of vaccination behavior:
      active decision-vaccinated, passive decision- vaccinated, passive decision- not
      vaccinated, active decision- not vaccinated, and antivaccination. A range of
      factors influenced participants in each decision-behavior state. Adolescents were
      often part of the decision-making process. Where adolescents were not involved,
      nonagreement sometimes occurred. CONCLUSION: We have presented a variety of paths
      girls and their parents experience regarding decision-making and behavior in HPV
      vaccination. Attitudes, past experiences, and worldviews contributed to this
      process.

PMID- 21090895
TI  - A differential deficit in time- versus event-based prospective memory in
      Parkinson's disease.
AB  - OBJECTIVE: The aim of the current study was to clarify the nature and extent of
      impairment in time- versus event-based prospective memory in Parkinson's disease
      (PD). Prospective memory is thought to involve cognitive processes that are
      mediated by prefrontal systems and are executive in nature. Given that
      individuals with PD frequently show executive dysfunction, it is important to
      determine whether these individuals may have deficits in prospective memory that
      could impact daily functions, such as taking medications. Although it has been
      reported that individuals with PD evidence impairment in prospective memory, it
      is still unclear whether they show a greater deficit for time- versus event-based
      cues. METHOD: Fifty-four individuals with PD and 34 demographically similar
      healthy adults were administered a standardized measure of prospective memory
      that allows for a direct comparison of time-based and event-based cues. In
      addition, participants were administered a series of standardized measures of
      retrospective memory and executive functions. RESULTS: Individuals with PD
      demonstrated impaired prospective memory performance compared to the healthy
      adults, with a greater impairment demonstrated for the time-based tasks. Time
      based prospective memory performance was moderately correlated with measures of
      executive functioning, but only the Stroop Neuropsychological Screening Test
      emerged as a unique predictor in a linear regression. CONCLUSIONS: Findings are
      interpreted within the context of McDaniel and Einstein's (2000) multiprocess
      theory to suggest that individuals with PD experience particular difficulty
      executing a future intention when the cue to execute the prescribed intention
      requires higher levels of executive control.

PMID- 21090896
TI  - The relationship between processing speed and working memory demand in systemic
      lupus erythematosus: evidence from a visual n-back task.
AB  - OBJECTIVE: Working memory (WM) deficits have been reported previously in systemic
      lupus erythematosus (SLE), but the relationship between information processing
      speed (PS) and WM deficits in SLE is unknown. This study examined whether or not
      PS slowing could account for the WM deficits observed in SLE. METHOD: A visual n
      back task was used to measure simple and complex PS and WM in 40 SLE patients and
      36 healthy controls. Simple PS was defined as reaction time (RT) to correct
      responses under a very low WM load condition (0-back), while complex PS was
      defined as RT to correct responses under moderate and high WM load conditions (1
      and 2-back). RESULTS: The results showed that SLE patients performed as well as
      the controls at the lower WM load conditions but had fewer correct responses than
      controls under the highest WM load condition (2-back). SLE patients had slower
      RTs than controls under all conditions, but they had relatively greater RT
      slowing than controls under the higher WM load conditions. Further, when RT for
      simple PS was subtracted from complex PS, SLE patients still showed slower
      complex PS for the 1- and 2-back compared with controls. Both simple and complex
      PS slowing were related to poorer accuracy scores on the 2-back condition, only
      for the SLE group. CONCLUSIONS: The n-back task provides a sensitive measure of
      PS and WM. The results suggest that PS deficits alone could not account for the
      WM deficits in SLE. Disease duration, disease activity, and depression did not
      appear to account for the observed PS and WM deficits.

PMID- 21090897
TI  - Working memory in mild cognitive impairment and Alzheimer's disease: contribution
      of forgetting and predictive value of complex span tasks.
AB  - OBJECTIVE: This study examines working memory (WM) in mild cognitive impairment
      (MCI) and Alzheimer's disease (AD). METHOD: Performances on sentence span and
      operation span were measured in individuals meeting criteria for MCI (n = 20) and
      AD (n = 16) as well as in healthy older adults (n = 20). In addition, the effect
      of retention interval was assessed by manipulating the length of first and last
      items of trials (long-short vs. short-long), as forgetting might contribute to
      impaired performance in AD and MCI. RESULTS: Results show a group effect (p <
      .001, eta2 = .47): In both conditions and for both material types, WM span is
      lower in AD than in MCI (p < .001), which in turn is lower than in healthy aging
      (p < .05). An effect of retention interval on complex span was found for all
      groups (p < .001, eta2 = .57), supporting a role for forgetting within WM. When
      computing a proportional interval effect (p < .05, eta2 = .12), it was found that
      persons with AD were more sensitive to retention interval than were healthy older
      adults (p < .05). Among persons with MCI, those who later showed significant
      clinical deterioration or progression to AD were more affected by retention
      interval (p < .05, eta2 = .28) than were those who remained stable. Furthermore,
      deficits in AD are associated with a higher proportion of intrusion errors,
      particularly those from the current trial (p < .05, eta2 = .15), which could
      reflect inhibitory processes. CONCLUSIONS: Overall, these results indicate
      impaired WM in age-related disorders with a gradient between MCI and AD.
      Retention interval increases deficit in persons with AD. It also shows potential
      in predicting a negative prognosis in those with MCI.

PMID- 21090898
TI  - Specific impairments of emotion perception in multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) often results in demyelination of a network of
      frontal-subcortical tracts involved in processing emotional information. We
      investigated the effect of MS on the ability to identify emotional and
      nonemotional information from static and dynamic stimuli and determined whether
      difficulties in emotion perception related to quality of life. METHOD: 32 MS and
      33 control participants, matched for age and education, identified emotions and
      nonemotional information from static images of faces and dynamic videos of people
      interacting. They also completed cognitive assessment and quality of life
      ratings. RESULTS: On the static face perception tasks, participants with MS
      performed more poorly than healthy controls on emotion perception, t(63) = 3.30,
      p < .01, d = .83, but not identity perception, t(63) = 1.18, d = .30. For the
      dynamic tasks, the MS group were impaired on emotion perception, t(63) = 3.41, p
      = .001, d = .86, but not age/gender perception, t(63) = 0.15, d = .04. Ratings of
      social and psychological aspects of quality of life in MS were related to emotion
      perception scores, controlling for disease severity and duration, age,
      depression, and cognitive function, with r2 ranging from .17 to .24. CONCLUSIONS:
      These results indicate a specific deficit in decoding static and dynamic
      information about emotion in MS, as compared to nonemotional information. There
      were specific relationships between emotion perception problems and poor social
      and psychological quality of life, indicating that emotional skills should be
      considered when evaluating functioning in MS.

PMID- 21090899
TI  - Altered probabilistic learning and response biases in schizophrenia: behavioral
      evidence and neurocomputational modeling.
AB  - OBJECTIVE: Patients with schizophrenia (SZ) show reinforcement learning
      impairments related to both the gradual/procedural acquisition of reward
      contingencies, and the ability to use trial-to-trial feedback to make rapid
      behavioral adjustments. METHOD: We used neurocomputational modeling to develop
      plausible mechanistic hypotheses explaining reinforcement learning impairments in
      individuals with SZ. We tested the model with a novel Go/NoGo learning task in
      which subjects had to learn to respond or withhold responses when presented with
      different stimuli associated with different probabilities of gains or losses in
      points. We analyzed data from 34 patients and 23 matched controls, characterizing
      positive- and negative-feedback-driven learning in both a training phase and a
      test phase. RESULTS: Consistent with simulations from a computational model of
      aberrant dopamine input to the basal ganglia patients, patients with SZ showed an
      overall increased rate of responding in the training phase, together with reduced
      response-time acceleration to frequently rewarded stimuli across training blocks,
      and a reduced relative preference for frequently rewarded training stimuli in the
      test phase. Patients did not differ from controls on measures of procedural
      negative-feedback-driven learning, although patients with SZ exhibited deficits
      in trial-to-trial adjustments to negative feedback, with these measures
      correlating with negative symptom severity. CONCLUSIONS: These findings support
      the hypothesis that patients with SZ have a deficit in procedural "Go" learning,
      linked to abnormalities in DA transmission at D1-type receptors, despite a "Go
      bias" (increased response rate), potentially related to excessive tonic dopamine.
      Deficits in trial-to-trial reinforcement learning were limited to a subset of
      patients with SZ with severe negative symptoms, putatively stemming from
      prefrontal cortical dysfunction.

PMID- 21090901
TI  - Neurocognition and functional outcome in early-onset schizophrenia and attention
      deficit/hyperactivity disorder: a 13-year follow-up.
AB  - OBJECTIVE: The relation between neurocognitive impairments and functional outcome
      has been documented in both early onset schizophrenia (EOS) and attention
      deficit/hyperactivity disorder (ADHD), but less is known about the long-term
      relation between these factors. The present study investigates how neurocognition
      at baseline is related to measures of functional outcome at 13-year follow-up in
      subjects with EOS and ADHD. METHOD: Subjects with EOS (n = 15), ADHD (n = 19),
      and healthy controls (n = 30) were followed up 13 years after initial assessment.
      All subjects were between 12 and 18 years of age at baseline and between 24 and
      30 at follow-up. They were retested at T2 with the same comprehensive
      neurocognitive test battery as used at T1, and reassessed with various symptom
      and behavior ratings and functional outcome measures. RESULTS: Both groups were
      characterized by reduced functional outcome at follow-up, although of different
      magnitude and type, compared with healthy controls. In the EOS group,
      neurocognitive baseline measures were associated with social functioning at
      follow-up (eta2 between .26 and .41), while for the ADHD group, no significant
      predictions were found. CONCLUSIONS: Adolescents with EOS and ADHD are
      characterized by poor functional outcome compared with healthy controls when
      reassessed as young adults. Executive function, memory and attention were related
      to social and community functioning in EOS. For ADHD no significant predictions
      were found although functional outcome was poor. For both groups treatment should
      focus on training of social skills and activities of daily living to enhance the
      long-term functional outcome. For EOS cognitive remediation should also be
      considered.

PMID- 21090900
TI  - Multimodal cuing of autobiographical memory in semantic dementia.
AB  - OBJECTIVE: Individuals with semantic dementia (SD) have impaired autobiographical
      memory (AM), but the extent of the impairment has been controversial. According
      to one report (Westmacott, Leach, Freedman, & Moscovitch, 2001), patient
      performance was better when visual cues were used instead of verbal cues;
      however, the visual cues used in that study (family photographs) provided more
      retrieval support than do the word cues that are typically used in AM studies. In
      the present study, we sought to disentangle the effects of retrieval support and
      cue modality. METHOD: We cued AMs of 5 patients with SD and 5 controls with
      words, simple pictures, and odors. Memories were elicited from childhood, early
      adulthood, and recent adulthood; they were scored for level of detail and
      episodic specificity. RESULTS: The patients were impaired across all time periods
      and stimulus modalities. Within the patient group, words and pictures were
      equally effective as cues (Friedman test; chi2 = 0.25, p = .61), whereas odors
      were less effective than both words and pictures (for words vs. odors, chi2 =
      7.83, p = .005; for pictures vs. odors, chi2 = 6.18, p = .01). There was no
      evidence of a temporal gradient in either group (for patients with SD, chi2 =
      0.24, p = .89; for controls, chi2 < 2.07, p = .35). CONCLUSIONS: Once the effect
      of retrieval support is equated across stimulus modalities, there is no evidence
      for an advantage of visual cues over verbal cues. The greater impairment for
      olfactory cues presumably reflects degeneration of anterior temporal regions that
      support olfactory memory.

PMID- 21090902
TI  - Evidence for hypodescent and racial hierarchy in the categorization and
      perception of biracial individuals.
AB  - Individuals who qualify equally for membership in two racial groups provide a
      rare window into social categorization and perception. In 5 experiments, we
      tested the extent to which a rule of hypodescent, whereby biracial individuals
      are assigned the status of their socially subordinate parent group, would govern
      perceptions of Asian-White and Black-White targets. In Experiment 1, in spite of
      posing explicit questions concerning Asian-White and Black-White targets,
      hypodescent was observed in both cases and more strongly in Black-White social
      categorization. Experiments 2A and 2B used a speeded response task and again
      revealed evidence of hypodescent in both cases, as well as a stronger effect in
      the Black-White target condition. In Experiments 3A and 3B, social perception was
      studied with a face-morphing task. Participants required a face to be lower in
      proportion minority to be perceived as minority than in proportion White to be
      perceived as White. Again, the threshold for being perceived as White was higher
      for Black-White than for Asian-White targets. An independent categorization task
      in Experiment 3B further confirmed the rule of hypodescent and variation in it
      that reflected the current racial hierarchy in the United States. These results
      documenting biases in the social categorization and perception of biracials have
      implications for resistance to change in the American racial hierarchy.

PMID- 21090903
TI  - Parts, cavities, and object representation in infancy.
AB  - Part representation is not only critical to object perception but also plays a
      key role in a number of basic visual cognition functions, such as figure-ground
      segregation, allocation of attention, and memory for shapes. Yet, virtually
      nothing is known about the development of part representation. If parts are
      fundamental components of object shape representation early in life, then the
      infant visual system should give priority to parts over other aspects of objects.
      We tested this hypothesis by examining whether part shapes are more salient than
      cavity shapes to infants. Five-month-olds were habituated to a stimulus that
      contained a part and a cavity. In a subsequent novelty preference test, 5-month
      olds exhibited a preference for the cavity shape, indicating that part shapes
      were more salient than cavity shapes during habituation. The differential
      processing of part versus cavity contours in infancy is consistent with theory
      and empirical findings in the literature on adult figure-ground perception and
      indicates that basic aspects of part-based object processing are evident early in
      life.

PMID- 21090904
TI  - Phonetic, phonemic, and phonological factors in cross-language discrimination of
      phonotactic contrasts.
AB  - Previous research indicates that multiple levels of linguistic information play a
      role in the perception and discrimination of non-native phonemes. This study
      examines the interaction of phonetic, phonemic and phonological factors in the
      discrimination of non-native phonotactic contrasts. Listeners of Catalan,
      English, and Russian are presented with an initial #CC-#CeC contrast in a
      discrimination task. For the Catalan group, the phonemes and their phonetic
      implementation were native, but the #CC phonotactics were not. For Russian
      listeners, the phonemes and phonetic implementation were not native but Russian
      allows a large number of #CC sequences. For English listeners, none of the
      phonetics, phonemes, nor phonotactics are native. Two task variables, stimuli
      length and order of presentation, were also manipulated. Results showed that the
      Russian listeners were most accurate overall, suggesting that the presence of the
      phonotactic structure in the listeners' native language may be more important
      than either phonemic or phonetic information. The interaction between the task
      manipulations and the linguistic variables is also addressed.

PMID- 21090906
TI  - Individual differences in working memory capacity predict retrieval-induced
      forgetting.
AB  - Selectively retrieving a subset of previously studied information enhances memory
      for the retrieved information but causes forgetting of related, nonretrieved
      information. Such retrieval-induced forgetting (RIF) has often been attributed to
      inhibitory executive-control processes that supposedly suppress the nonretrieved
      items' memory representation. Here, we examined the role of working memory
      capacity (WMC) in young adults' RIF. WMC was assessed by means of the operation
      span task. Results revealed a positive relationship between WMC and RIF, with
      high-WMC individuals showing more RIF than low-WMC individuals. In contrast,
      individuals showed enhanced memory for retrieved information regardless of WMC.
      The results are consistent with previous individual-differences work that
      suggests a close link between WMC and inhibitory efficiency. In particular, the
      finding supports the inhibitory executive-control account of RIF.

PMID- 21090905
TI  - What are the shapes of response time distributions in visual search?
AB  - Many visual search experiments measure response time (RT) as their primary
      dependent variable. Analyses typically focus on mean (or median) RT. However,
      given enough data, the RT distribution can be a rich source of information. For
      this paper, we collected about 500 trials per cell per observer for both target
      present and target-absent displays in each of three classic search tasks: feature
      search, with the target defined by color; conjunction search, with the target
      defined by both color and orientation; and spatial configuration search for a 2
      among distractor 5s. This large data set allows us to characterize the RT
      distributions in detail. We present the raw RT distributions and fit several
      psychologically motivated functions (ex-Gaussian, ex-Wald, Gamma, and Weibull) to
      the data. We analyze and interpret parameter trends from these four functions
      within the context of theories of visual search.

PMID- 21090907
TI  - Diabetes risk reduction behaviours of rural postpartum women with a recent
      history of gestational diabetes.
AB  - INTRODUCTION: For most women, gestational diabetes is temporary; however, an
      episode of gestational diabetes mellitus (GDM) confers an approximately seven
      fold increased risk of developing type 2 diabetes mellitus. OBJECTIVE: To examine
      readiness to adopt diabetes risk reduction behaviours and the prevalence of these
      behaviours among rural women with GDM during their last pregnancy. METHODS: The
      study design was a self-administered mailed questionnaire seeking information
      about demographics, stage of change, physical activity level and dietary fat
      intake. SETTING: Regional outpatient context. PARTICIPANTS: Women with a single
      episode of GDM between 1 July 2001 and 31 December 2005 (n = 210). MAIN OUTCOME
      MEASURES: Stage of change for physical activity, weight loss and reducing dietary
      fat behaviour; meeting activity targets, body mass index (BMI) and dietary fat
      score. RESULTS: Eighty-four women returned completed questionnaires (40% response
      rate). Of the 77 women eligible (mean age 35 +/- 3.8 years), 58% met recommended
      activity targets. Sixty-three percent of women were overweight or obese: mean BMI
      29.6 kg/m2 (+/- 7.30). Women reported a high level of preparedness to engage in
      physical activity, weight loss and reduction of fat intake. Thirty-nine percent
      of women had not had any postpartum follow-up glucose screening. Women who
      remembered receiving diabetes prevention information were significantly more
      likely to meet physical activity targets (p<0.05). CONCLUSIONS: Readiness to
      engage in behaviour change was high among this group of rural women for all three
      diabetes risk reduction behaviours measured. However, despite a high proportion
      of women meeting activity targets and reducing fat intake, the majority of women
      remained overweight or obese. Postpartum follow-up glucose testing needs to be
      improved and the impact of diabetes prevention information provided during
      pregnancy warrants further study.

PMID- 21090908
TI  - Trachoma in northern Ghana: a need for further studies.
AB  - BACKGROUND: The northern Ghana Upper East Region [UER], Upper West Region [UWR],
      and Northern Region (NR) lie within the African trachoma belt. The 3 regions
      share common features of poverty, dryness, dusty environments, and poor
      environmental hygiene. Trachoma has been identified previously in the NR and the
      UWR as a disease of public health importance and a control program is underway.
      PURPOSE: To establish baseline prevalence and risk factor parameters in the Upper
      East for possible control of trachoma in the region. METHODS: Population-based
      cross-sectional survey using multi-staged cluster sampling techniques was used.
      In all 26,323 participants from 4,374 households in 160 communities were examined
      with a 2.5x magnifying binocular loupe for trachoma; 7,763 were children aged 1-9
      years and 15,191 were aged 15 years and over. RESULTS: Only 3 children were
      identified with active trachoma (trachoma with follicles, TF = 1; trachoma with
      intense inflammation, TI = 2) giving regional prevalence of 0.01% (Confidence
      Limits, CL: 0.0-0.1) for TF and 0.03% (CL: 0.0-0.1) for TI. Trachomatous
      trichiasis was measured at 0.05% (CL: 0.0-0.1) while children with clean faces
      was measured at 95.5%. Only 3.6% of the examined households in the region had
      access to a toilet facility. CONCLUSION: Trachoma is not a disease of public
      health importance in the UER of Ghana despite being in a trachoma endemic zone
      and sharing the necessary risk factors for the disease.

PMID- 21090909
TI  - Barriers to the implementation of the SAFE strategy to combat hyperendemic
      trachoma in Australia.
AB  - OBJECTIVE: Australia is the only developed country in the world that still has
      endemic levels of blinding trachoma. The SAFE (Surgery, Antibiotics, Facial
      cleanliness, Environmental improvement) strategy is an effective public health
      intervention that has been successfully used to eliminate blinding trachoma in
      some of the poorest countries of the world. Yet the SAFE strategy has not been
      systematically implemented in Australia. We undertook semi-structured interviews
      to identify some of barriers to the implementation of the SAFE strategy within
      remote indigenous communities of Australia. METHODS: Health care professionals
      who were responsible for delivering trachoma control programs throughout the
      Northern Territory were asked to participate in a semi-structured interview.
      Quantitative analysis was performed using an existing strategic management
      framework. RESULTS: Fourteen individuals were interviewed. Responses were grouped
      into 19 categories; 12 from the existing strategic management framework and 7
      additional categories that were created for ideas unique to the trachoma control
      program in Australia. CONCLUSIONS: A number of key themes emerged from the
      interview and are presented in a literary style. From these key themes critical
      success factors for the implementation of a sustainable trachoma control program
      were identified. With the election of the Rudd government there has been a
      renewed interest in "closing the gap" between the health of indigenous and non
      indigenous Australians. A federal government funding package of $58 million over
      four years has just been announced to tackle trachoma. It is hoped that the
      findings of this research can assist in making sure that money achieves its goal.

PMID- 21090910
TI  - Oman's progress towards reaching "Ultimate Intervention Goals" for the surgery
      "S" component of SAFE strategy for the elimination of blinding trachoma in 2008.
AB  - BACKGROUND: A community based survey for Trachomatous Trichiasis (TT) was
      conducted in the high (TT >5% in 1997) and meso endemic areas (TT 1% to 5% in
      1997) of Oman during 2008-09. METHODS: Investigators examined Omanis 40 age years
      and older from randomly selected villages. Eyes were examined for TT and vision.
      The medical history of surgery and advice given for TT surgery were recorded. The
      TT cases that were unadvised by health staff were defined as un-approached cases.
      Cluster adjusted prevalence of TT and risk of TT by gender were estimated.
      RESULT: We examined 4,951 of 5,268 persons in high-endemic areas and 965 of 993
      (97.2%) persons in meso-endemic areas. The cluster adjusted prevalence of TT in
      the high and meso endemic areas were 7.54% (95% Confidence Interval [CI] 6.78
      8.30) and 1.69% (95% CI 0.88-2.50) respectively. There were 5 TT patients in high
      endemic areas and none in meso-endemic areas who were not approached or managed
      in the past. The prevalence of TT across all ages was less than 1 per 1,000 of
      the population in all wilayats of Oman. Females had a significantly higher risk
      of cluster adjusted TT compared to males (Odds Ratio = 1.87 [95% CI 1.85-1.89]).
      The prevalence of blindness was 0.5% among TT cases in high endemic areas.
      CONCLUSION: Oman seems to have reached the Ultimate Intervention Goals (UIGs) of
      the "S" (Surgery) component in 2008 in high and meso-endemic areas. The efforts
      of existing eye services could be better evaluated if un-approached TT cases are
      used to calculate the TT prevalence. Oman needs to focus more on females with TT
      to reach the UIGs.

PMID- 21090911
TI  - A Dutch ICF version of the Activity Inventory: results from focus groups with
      visually impaired persons and experts.
AB  - PURPOSE: To develop a valid and reliable instrument to systematically investigate
      visual rehabilitation needs of visually impaired older adults, which is
      compatible with the "International Classification of Functioning, Disability and
      Health" (ICF) structure: a new Dutch ICF version of the Activity Inventory (D
      AI). METHODS: The original AI was translated, adjusted and expanded. After
      studying literature and investigating patient records, focus group discussions
      were conducted until the input was just confirmatory. Six (n = 41) and seven (n =
      50) discussions with patients and professionals respectively contributed to the
      first draft of the D-AI, which was further improved by professionals. RESULTS:
      The D-AI now consists of 10 domains, 68 goals and 813 tasks. Goals are organized
      into the "Activities and Participation" domains of the ICF. The original routing
      was maintained; only tasks organized under important (0 [not important] to 3
      [very important]) and difficult (0 [not difficult] to 4 [impossible]) goals were
      assessed. CONCLUSION: Rehabilitation needs can be organized in the "Activities
      and Participation" domains of the ICF. The D-AI offers a way of systematically
      assessing and measuring functional limitations and disabilities, and provides
      detailed information about activities that are needed to perform a certain goal.
      Focus group discussions with Dutch patients and experts revealed additional items
      that will probably be relevant for other populations. Involving patients in the
      first step of the developing process is important to provide face and content
      validity. The D-AI can prioritize rehabilitation goals by multiplying importance
      and difficulty scores, which is helpful in formulating a rehabilitation plan.

PMID- 21090912
TI  - The impact of cataract surgery on health related quality of life in Kenya, the
      Philippines, and Bangladesh.
AB  - PURPOSE: To assess the impact of cataract surgery on vision related quality of
      life (VRQoL) and generic health related quality of life (HRQoL) in Kenya,
      Bangladesh and the Philippines. METHODS: A multi-center intervention study was
      conducted. At baseline 651 cases aged >=50 years with visually impairing cataract
      (corrected visual acuity (VA) <6/24) and 561 age- gender-matched controls with
      normal vision (VA>6/18) were interviewed about VRQoL (using the World Health
      Organization/ Prevention of Blindness and Deafness 20-item Visual Functioning
      Questionnaire [WHO/PBD VF20]) and generic HRQoL (EuroQol). Cases were offered
      free/subsidized cataract surgery. Approximately 1 year later participants were re
      interviewed. RESULTS: Response rate at follow up was 84% for operated cases and
      80% for controls. At baseline, cases had significantly poorer VRQoL scores, were
      more likely to report problems with the EuroQol 5D five descriptive (EQ-SD)
      domains (mobility, daily activities, self-care, pain, depression/anxiety) and had
      significantly poorer self-rated health compared to controls. At follow up VRQoL
      scores of operated cases improved significantly to approximately equal those of
      controls. Effect sizes were large (> 0.8) regardless of pre-operative VA. Poor
      outcome from surgery (VA < 6/60) was associated with smaller VRQoL gains. Among
      operated cases frequency of reported problems with all the EQ-5D reduced
      significantly compared to baseline in Kenya and the Philippines, and in mobility,
      daily activities and self-care in Bangladesh. Self-rated health scores increased
      significantly in each country. HRQoL of controls remained stable from baseline to
      follow up. CONCLUSION: This study among adults undergoing cataract surgery in 3
      different low-income settings found evidence of improved VRQoL and generic HRQoL
      to approximately equal that of controls with normal vision.

PMID- 21090913
TI  - Health risk profile for older adults with blindness: an application of the
      International Classification of Functioning, Disability, and Health framework.
AB  - PURPOSE: To develop a health risk profile for adults age 65 years or older with
      blindness, using the International Classification of Functioning, Disability and
      Health (ICF) as our conceptual framework. METHODS: We combined and analyzed data
      from the 2000-2006 National Health Interview Survey after backcoding questions to
      the ICF. We compared older adults with blindness (n = 477) and older adults with
      vision loss but not blindness (n = 6,721) with older adults who reported no
      vision loss (n = 33,497) for the following outcome measures: demographics,
      functional limitations (self-care, social participation, and mobility
      limitations), level of psychological distress, physical health status, selected
      chronic conditions and health risk behaviors (smoking, alcohol use, obesity, and
      physical inactivity). RESULTS: Older adults with blindness were more likely to be
      poorer, older, and less educated than older adults without vision loss. They were
      also more likely to have fair to poor health; to have difficulty walking; to
      experience diabetes, heart problems, and breathing problems; and to be physically
      inactive, compared with older adults reporting vision loss but not blindness and
      older adults without vision loss. CONCLUSION: Older adults with blindness face
      significant health disparities that can diminish their quality of life without
      timely, disability-sensitive interventions to address serious psychological
      distress and physical inactivity.

PMID- 21090914
TI  - The methodology of visual field testing with frequency doubling technology in the
      National Health and Nutrition Examination Survey, 2005-2006.
AB  - PURPOSE: To describe the frequency doubling technology (FDT) methodology to
      measure visual field loss in the National Health and Nutrition Examination Survey
      and to evaluate data reliability. METHODS: Participants aged 40 years and older
      were eligible (n = 2,529) for 2 visual field tests per eye performed with the
      Humphrey Matrix N-30-5 screening test. Visual field loss was determined using a 2
      2-1 algorithm requiring 2 complete tests per eye, with at least 2 abnormal field
      results in each test, and 1 common abnormal field. RESULTS: Response rate was
      86.2%. Time constraints were the main reason for no exam (55.6%). Median times
      were: single test, 37 seconds; entire exam, 9.1 minutes. When defining
      reliability based on <= 1/3 blind spots, <= 1/3 false positive tests, and
      technician noted proper fixation, 80.1% of examined adults had 2 reliable tests
      for both eyes; an additional 13.4% had 2 reliable tests for 1 eye. Increasing
      age, decreasing visual acuity, and the presence of self-reported glaucoma
      resulted in decreased examination rates, increased test times, and decreased data
      reliability. Sensitivity and specificity to detect persons with glaucoma was
      54.8% and 91.9%, respectively. CONCLUSIONS: FDT is a feasible, fast, and reliable
      method for visual field loss screening in a population-based U.S. study, with an
      86.2% response rate, median exam time ~9 minutes, and nearly 95% of examined
      participants having complete, reliable results in 1 or both eyes.

PMID- 21090915
TI  - Safety and reliability of hepatic radiofrequency ablation near the inferior vena
      cava: an experimental study.
AB  - PURPOSE: The heat-sink effect produced by rapid blood flow through large vessels
      (diameter (D) >= 5 mm) is an important factor that influences ablation zone size
      after radiofrequency ablation (RFA). Currently, however, the interactions between
      hepatic RFA lesions and large vessels are not well understood. The purpose of
      this study was to examine the effects of RFA lesions occurring near large vessels
      (D >= 5 mm) in the canine liver. MATERIALS AND METHODS: Thirty healthy adult
      mongrel dogs were used, with 15 dogs randomly assigned to groups I and II. In
      group I, the closest distance from the tip of the RFA electrode to the large
      vessel (D >= 5 mm) was more than 20 mm; in group II, this distance to the wall of
      the inferior vena cava (IVC) was no more than 5 mm. RFA was performed on the
      liver of each dog according to standard procedures. The blood flow velocity of
      the IVC, the computerised tomography (CT), the pathological characteristics of
      the RFA lesions and procedure-related complications were examined. RESULTS: No
      death or complications occurred in any dogs. Vascular walls were not affected,
      except for when the tips of the electrode stuck to the IVC. The coagulative
      necrosis region was decreased, and its shape was fusiform close to the IVC. Some
      normal hepatic cells were found in the necrotic region near the IVC. CONCLUSIONS:
      It is both safe and feasible to perform RFA near the IVC. The shape and size of
      the coagulation zone should be considered when electrodes are placed in this
      area. Near the IVC, the size of the coagulation zone was decreased, and it was
      incompletely formed.

PMID- 21090916
TI  - Individual and synergistic cytokine effects controlling the expansion of cord
      blood CD34(+) cells and megakaryocyte progenitors in culture.
AB  - BACKGROUND AIMS: Expansion of hematopoietic progenitors ex vivo is currently
      investigated as a means of reducing cytopenia following stem cell
      transplantation. The principal objective of this study was to develop a new
      cytokine cocktail that would maximize the expansion of megakaryocyte (Mk)
      progenitors that could be used to reduce periods of thrombocytopenia. METHODS: We
      measured the individual and synergistic effects of six cytokines [stem cell
      factor (SCF), FLT-3 ligand (FL), interleukin (IL)-3, IL-6, IL-9 and IL-11]
      commonly used to expand cord blood (CB) CD34(+) cells on the expansion of CB Mk
      progenitors and major myeloid populations by factorial design. RESULTS: These
      results revealed an elaborate array of cytokine individual effects complemented
      by a large number of synergistic and antagonistic interaction effects. Notably,
      strong interactions with SCF were observed with most cytokines and its
      concentration level was the most influential factor for the expansion and
      differentiation kinetics of CB CD34(+) cells. A response surface methodology was
      then applied to optimize the concentrations of the selected cytokines. The newly
      developed cocktail composed of SCF, thrombopoietin (TPO) and FL increased the
      expansion of Mk progenitors and maintained efficient expansion of clonogenic
      progenitors and CD34(+) cells. CB cells expanded with the new cocktail were shown
      to provide good short- and long-term human platelet recovery and lymphomyeloid
      reconstitution in NOD/SCID mice. CONCLUSIONS: Collectively, these results define
      a complex cytokine network that regulates the growth and differentiation of
      immature and committed hematopoietic cells in culture, and confirm that cytokine
      interactions have major influences on the fate of hematopoietic cells.

PMID- 21090917
TI  - Therapeutic granulocyte transfusions for the treatment of febrile neutropenia in
      patients with hematologic diseases: a 10-year experience at a single institute.
AB  - BACKGROUND AIMS: This single-center 10-year retrospective study assessed clinical
      efficacies and adverse events and determined prognostic factors in patients with
      hematologic disease and febrile neutropenia treated with granulocyte transfusions
      (GT) from unrelated healthy donors stimulated with recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) and dexamethasone. METHODS: Between September
      1999 and June 2009, 1027 therapeutic GT were performed for the treatment of 170
      episodes of febrile neutropenia in 157 patients. Efficacy analysis included 979
      GT for 138 episodes in 128 patients who received at least three GT per episode.
      Adverse event analysis included all patients who received at least one GT.
      RESULTS: The median granulocyte dose was 0.96 * 10(9)/kg/transfusion (range 0.47
      1.80 * 10(9)/kg/transfusion). Infection was controlled in 73 episodes (52.9%).
      The 28-day infection-related survival rate was 64.7 +/- 4.1%. The dose of
      granulocytes transfused did not correlate with clinical outcome. Multivariate
      analysis revealed that septic shock and pneumonia/multiple primary infection
      sites were related to infection control failure. Furthermore, refractory
      underlying disease and septic shock were associated with shorter infection
      related survival. Massive hemoptysis (3.5%) and respiratory failure (5.9%)
      occurred in a few patients. Prior pneumonic infiltration, azotemia and a larger
      volume of daily GT were associated with serious respiratory complications.
      CONCLUSIONS: GT therapy is a viable adjunctive treatment option for febrile
      neutropenia as a bridge to autologous hematopoietic recovery in patients with
      hematologic disease with tolerable toxicity. GT therapy requires close monitoring
      in patients with prior pneumonic infiltration and azotemia. It is recommended
      that transfusion with higher volumes is avoided.

PMID- 21090918
TI  - Mesenchymal stromal cells are present in the heart and promote growth of adult
      stem cells in vitro.
AB  - BACKGROUND AIMS: For many years the human heart has been considered a terminally
      differentiated organ with no regenerative potential after injury. Recent studies,
      however, have cast doubt on this long-standing dogma. The objective of this study
      was to investigate the presence of and characterize mesenchymal stromal cells
      (MSC) in the adult mouse heart. The impact of MSC on growth and differentiation
      of adult cardiac stem cells (CSC) was also analyzed. METHODS: A combination of
      lineage-negative/c-kit-negative (Lin(-)/c-kit(-)) immunoselection with a plastic
      adhesion technique was used to isolate cardiac-derived MSC. The differentiation
      capacity and expression of surface markers were analyzed. To investigate the
      impact of MSC on growth and differentiation of adult CSC, Green Fluorescent
      Protein (GFP(+)) adult CSC were co-cultured with GFP(-) cardiac-derived MSC.
      RESULTS: MSC were present in the adult mouse heart and they met the criteria
      established to define mouse MSC. They expressed surface markers and were able to
      differentiate, in a controlled manner, into multiple lineages. In addition,
      cardiac-derived MSC promoted the survival and expansion of adult CSC in vitro.
      CONCLUSIONS: MSC can be isolated from the mouse heart and they promote growth and
      differentiation of adult CSC. The findings from this study could have a
      significant beneficial impact on future heart failure treatment. Co-culture and
      co-implantation of cardiac-derived MSC with adult CSC could provide extensive
      cardiac regeneration and maintenance of the CSC population after implanted into
      the heart.

PMID- 21090919
TI  - Gold nanoparticle trafficking of typically excluded compounds across the cell
      membrane in JB6 Cl 41-5a cells causes assay interference.
AB  - Nanoparticles (NP) often interfere with the mechanism and interpretation of high
      throughput in vitro toxicity assays. This interference may occur at any time
      during the assay and spans most NP systems. This study reports on a specific type
      of gold NP assay interference, where unmodified gold NPs were able to traffic
      certain assay molecules that contained primary amines across the cell membrane
      resulting in false positive results for toxicity assays. The enhanced assay
      molecule permeability was eliminated when the gold NP surface was both sterically
      and chemically blocked by polyethylene glycol (PEG). The results support the
      growing consensus that appropriate controls and assay validation should occur
      prior to interpretation of results of assays using NP.

PMID- 21090920
TI  - STEM mode in the SEM: a practical tool for nanotoxicology.
AB  - The addition of a transmitted electron detector to a scanning electron microscope
      (SEM) allows the recording of bright and dark field scanning transmission
      electron microscope (STEM) images and the corresponding in-lens secondary
      electron images from the same region of a thin sample. These combined imaging
      techniques have been applied here to the analysis of ultrathin sections of cells
      exposed in vitro to nanomaterials for toxicology investigation. Electron
      microscopy in general permits the exact nature of the interaction of
      nanomaterials and cells to be elucidated, and in addition the use of STEM mode in
      the SEM enables the easy identification and exclusion of artefacts produced by
      ultramicrotome sectioning. The imaging and analysis obtained by using the STEM
      mode in the SEM configuration from three different nanomaterial systems of
      importance (iron oxide nanoparticles, single-walled carbon nanotubes and cadmium
      selenide quantum dots) indicate that it is a simple, practical and cost-effective
      tool for nanotoxicological research.

PMID- 21090921
TI  - Just a spoonful of sugar helps the blood pressure go up.

PMID- 21090922
TI  - The doctor needs to see you now: accelerating the care of patients with
      uncontrolled hypertension.

PMID- 21090924
TI  - Combination of telmisartan plus amlodipine in the treatment of hypertension:
      review of results.
AB  - The rate of control of hypertension remains suboptimal despite widespread
      educational programs and an increasing number of novel medications. The
      combination of drugs with different mechanisms of action has become an
      alternative to improve blood pressure reduction and control, enhance adherence to
      the treatment and reduce adverse events. Telmisartan and amlodipine in
      monotherapy provide effective blood pressure lowering at all clinically relevant
      doses, but less than 50% of stage 1 and 2 achieve the target blood pressure. This
      article presents most of the relevant results of combinations of telmisartan plus
      amlodipine, at different doses, in hypertensive patients and a post hoc analysis
      of subgroups including the elderly, Type 2 diabetics, those with systolic
      hypertension and obese patients.

PMID- 21090925
TI  - Detecting, predicting and modifying cardiovascular risk: new and developing
      strategies.
AB  - Cardiovascular disease is a leading cause of mortality across Europe and the USA.
      Epidemiological studies and randomized clinical trials provide strong evidence
      that coronary disease is largely preventable and can be attributed principally to
      nine modifiable risk factors. However, a large proportion of coronary events
      occur in individuals who have intermediate levels of these risk factors,
      motivating the search for novel markers to improve screening and risk
      stratification. Work presented at the 78th European Atherosclerosis Society
      Congress outlined challenges faced in primary prevention as well as novel
      findings for risk factors. This article focuses on some of these factors, as well
      as risk prediction and detection, and concludes with the current state of
      antiatherogenic treatment strategies.

PMID- 21090926
TI  - Choosing an antihypertensive combination with a more efficient central blood
      pressure reduction.
AB  - Not all blood pressure (BP)-lowering agents have the same effect on central BP,
      but we know that central BP, in itself, is a risk factor for cardiovascular
      diseases. Therefore, antihypertensive agents should ideally also have a central
      BP-lowering effect. In this paper the authors evaluate the effect of adding a
      calcium channel blocker to a beta-blocker. The results show this combination does
      not reverse the lesser effect of beta-blockers on central BP, and that the
      combination of valsartan plus amlodipine is more effective in lowering central BP
      than a combination of amlodipine plus atenolol.

PMID- 21090927
TI  - Current diagnosis and treatment of primary aldosteronism.
AB  - Primary aldosteronism is more common than previously recognized but much less
      common than most experts in this arena have recently stated. The recognition of
      autonomous hyperaldosteronism is not difficult but the identification of the
      source of excess aldosterone requires a costly and difficult procedure. Most
      patients with hyperaldosteronism turn out to have bilateral adrenal hyperplasia
      for which medical therapy with an aldosterone blocker is indicated. Many of these
      patients are not hypokalemic and can safely be treated without the need for a
      costly and usually negative work-up.

PMID- 21090928
TI  - Aging and hypertension.
AB  - Aging is known to be a dominant risk factor in the progression of hypertension.
      Thus, accompanied by an increasing mean age of the population in developed
      countries, prevention and management of hypertension in the elderly is a task of
      pressing urgency. Age-associated blood pressure elevation is a result of the
      aging process in organ systems, which play a key role in the regulation of blood
      pressure. In addition, advanced aging of the cardiovascular system contributes to
      the presence of a varied phenotype in elderly hypertension, such as nocturnal
      hypertension and morning hypertension. Therefore, in order to detect and treat
      age-associated hypertension appropriately, it is important to assess ambulatory
      blood pressure monitoring throughout the 24-h period.

PMID- 21090929
TI  - Hypertension alone or related to the metabolic syndrome in postmenopausal women.
AB  - Cardiovascular risk is poorly perceived by women, especially during the peri- and
      postmenopausal period when susceptibility to cardiovascular events increases.
      Nevertheless in Europe, 55% of women versus 43% of men currently die of
      cardiovascular disease. Blood pressure is one of the most powerful and accurate
      determinants of cardiovascular status and risk. Despite its importance,
      hypertension is often underestimated and undiagnosed, especially in women.
      Various mechanisms are implicated to play a role in the blood pressure increase
      in women at the time of menopause. Hypertension can be considered an isolated
      disease, more typical of elderly women, or part of the metabolic syndrome, more
      frequent in early postmenopausal women. The metabolic syndrome, a clustering of
      lipid and nonlipid cardiovascular risk factors, is estimated to affect
      approximately 20-30% of the middle-aged population and its prevalence appears to
      be increasing in the worldwide population.

PMID- 21090931
TI  - Hypothyroidism and hypertension.
AB  - Hypothyroidism has been recognized as a cause of secondary hypertension. Previous
      studies on the prevalence of hypertension in subjects with hypothyroidism have
      demonstrated elevated blood pressure values. Increased peripheral vascular
      resistance and low cardiac output has been suggested to be the possible link
      between hypothyroidism and diastolic hypertension. The hypothyroid population is
      characterized by significant volume changes, initiating a volume-dependent, low
      plasma renin activity mechanism of blood pressure elevation. This article
      summarizes previous studies on the impact of hypothyroidism on blood pressure and
      early atherosclerotic process.

PMID- 21090930
TI  - Pulmonary hypertension in women.
AB  - Female predominance in pulmonary arterial hypertension (PAH) has been known for
      several decades and recent interest in the effects of sex hormones on the
      development of disease has substantially increased our understanding of this
      epidemiologic observation. Basic science data suggest a beneficial effect of
      estrogens in the pulmonary vasculature both acutely and chronically, which seems
      to contradict the known predilection in women. Recent human and rodent data have
      suggested that altered levels of estrogen, differential signaling and altered
      metabolism of estrogens in PAH may underlie the gender difference in this
      disease. Studies of the effects of sex hormones on the right ventricle in animal
      and human disease will further aid in understanding gender differences in PAH.
      This article focuses on the effects of sex hormones on the pulmonary vasculature
      and right ventricle on both a basic science and translational level.

PMID- 21090932
TI  - Office, ambulatory and home blood pressure measurement in children and
      adolescents.
AB  - There is an increasing interest in pediatric hypertension, the prevalence of
      which is rising in parallel with the obesity epidemic. Traditionally the
      assessment of hypertension in children has relied on office blood pressure (BP)
      measurements by the physician. However, as in adults, office BP might be
      misleading in children mainly due to the white coat and masked hypertension
      phenomena. Thus, out-of-office BP assessment, using ambulatory or home
      monitoring, has gained ground for the accurate diagnosis of hypertension and
      decision-making. Ambulatory monitoring is regarded as indispensable for the
      evaluation of pediatric hypertension. Preliminary data support the usefulness of
      home monitoring, yet more evidence is needed. Office, ambulatory and home BP
      normalcy tables providing thresholds for diagnosis have been published and should
      be used for the assessment of elevated BP in children.

PMID- 21090933
TI  - Blood pressure control in resistant hypertension: new therapeutic options.
AB  - Resistant hypertension, namely the hypertensive state characterized by the
      inability of multiple antihypertensive drug interventions to lower blood pressure
      to goal levels, represents a condition frequently detected in clinical practice.
      Its main features are represented by its heterogeneous etiology as well as its
      very high cardiovascular risk. This latter peculiarity has implemented the
      research for new approaches to the treatment of the disease. This article will
      focus on two of them, namely carotid baroreceptor electric stimulation and the
      renal denervation procedure. Clinical studies and large-scale clinical trials are
      presently ongoing with the aim of defining the long-term efficacy and safety
      profile of the two interventions.

PMID- 21090934
TI  - Current status of blood pressure management after stroke.
AB  - Stroke is a leading cause of mortality and long-term disability in the western
      world, accounting for 5% of the UK health budget. Consequently, it has been the
      major focus of recent healthcare advances. Physiological disturbances are common
      following an acute stroke, chiefly blood pressure (BP) abnormalities (high and
      'relatively' low BP), which indicate adverse prognosis. While pilot studies
      suggest that early intervention to moderate both extremes of BP may improve
      outcomes, definitive evidence is awaited from ongoing research. Long-term
      elevated BP is the most prevalent risk factor for future stroke, with a
      comprehensive evidence base supporting BP reduction to reduce the risk of
      vascular events, including stroke. However, adherence to secondary preventive
      medications, including antihypertensive agents, remains poor. This article
      summarizes the current understanding of the role of BP in stroke, focusing on the
      management of BP for secondary prevention. Further emphasis is placed on
      identifying deficiencies in long-term management; barriers to improved
      application and potential interventions to overcome these barriers are
      summarized.

PMID- 21090935
TI  - Role of vitamin D in arterial hypertension.
AB  - Vitamin D deficiency is highly prevalent and may contribute to arterial
      hypertension. The antihypertensive effects of vitamin D include suppression of
      renin and parathyroid hormone levels and renoprotective, anti-inflammatory and
      vasculoprotective properties. Low 25-hydroxyvitamin D levels, which are used to
      classify the vitamin D status, are an independent risk factor for incident
      arterial hypertension. Meta-analyses of randomized controlled trials showed that
      vitamin D supplementation reduces systolic blood pressure by 2-6 mmHg. However,
      further studies are needed before drawing a final conclusion on the effect of
      vitamin D therapy on blood pressure and cardiovascular risk. In our current
      clinical practice we should take into account the high prevalence of vitamin D
      deficiency, the easy, cheap and safe way by which it can be supplemented and the
      promising clinical data suggesting that vitamin D might be useful for the
      treatment of arterial hypertension as well as other chronic diseases. Therefore,
      we recommend that testing for and treating vitamin D deficiency in patients with
      arterial hypertension should be seriously considered.

PMID- 21090936
TI  - Valsartan-amlodipine-hydrochlorothiazide: the definitive fixed combination?
AB  - A significant proportion of patients with hypertension will need three or more
      antihypertensive agents to achieve blood pressure goals, particularly those at
      higher risk. On the other hand, fixed combinations provide an extra beneficial
      effect, as they improve medication adherence and, secondarily, the attainment of
      blood pressure goals during follow-up. Triple therapy is recommended in the
      treatment of hypertension in those patients not adequately controlled with two
      antihypertensive drugs. In this context, guidelines recommend the combination of
      a renin-angiotensin system inhibitor, a calcium channel blocker and a diuretic.
      The triple fixed combination of valsartan-amlodipine-hydrochlorothiazide has been
      shown to be an effective and safe therapy for treating hypertension and seems a
      logical approach for those patients uncontrolled with two antihypertensive agents
      as well as in those patients already treated with three drugs to improve
      treatment compliance. In this article, available evidence about the efficacy and
      tolerability of the triple fixed combined therapy valsartan-amlodipine
      hydrochlorothiazide for the treatment of hypertension is updated.

PMID- 21090937
TI  - Treating atherosclerosis: the potential of Toll-like receptors as therapeutic
      targets.
AB  - Atherosclerosis is an inflammatory disease with a strong involvement of innate
      immunity. Toll-like receptors (TLRs) are the best-characterized pattern
      recognition receptors of the innate immune system. Almost all cell types in
      lesions, inflammatory leukocytes and resident vascular cells alike express TLRs.
      TLRs are able to sense modified lipids, enhance foam cell formation, induce
      leukocyte recruitment, and increase cytokine and matrix metalloproteinase
      production within atherosclerotic lesions. As such, TLRs represent an important
      link between atheroma and inflammation, making them attractive targets for the
      treatment of cardiovascular disease. Novel TLR-specific biologics are being
      developed and tested in other inflammatory diseases. This article will describe
      the exciting potential of TLRs as therapeutic targets for the treatment of
      atherosclerosis and will also highlight the potential challenges in the clinical
      application of TLR-based therapeutics in cardiovascular disease.

PMID- 21090939
TI  - Combined formative and summative professional behaviour assessment approach in
      the bachelor phase of medical school: a Dutch perspective.
AB  - BACKGROUND: Teaching and assessment of professional behaviour (PB) has been
      receiving increasing attention in the educational literature and educational
      practice. Although the focus tends to be summative aspects, it seems perfectly
      feasible to combine formative and summative approaches in one procedural
      approach. AIMS AND METHOD: Although, many examples of frameworks of
      professionalism and PB can be found in the literature, most originate from North
      America, and only few are designed in other continents. This article presents the
      framework for PB that is used at Maastricht medical school, the Netherlands.
      RESULTS: The approach to PB used in the Dutch medical schools is described with
      special attention to 4 years (2005-2009) of experience with PB education in the
      first 3 years of the 6-year undergraduate curriculum of Maastricht medical
      school. Future challenges are identified. CONCLUSIONS: The adages 'Assessment
      drives learning' and 'They do not respect what you do not inspect' [Cohen JJ.
      2006. Professionalism in medical education, an American perspective: From
      evidence to accountability. Med Educ 40, 607-617] suggest that formative and
      summative aspects of PB assessment can be combined within an assessment
      framework. Formative and summative assessments do not represent contrasting but
      rather complementary approaches. The Maastricht medical school framework combines
      the two approaches, as two sides of the same coin.

PMID- 21090940
TI  - Students' reflections in a portfolio pilot: highlighting professional issues.
AB  - BACKGROUND: Portfolios are highlighted as potential assessment tools for
      professional competence. Although students' self-reflections are considered to be
      central in the portfolio, the content of reflections in practice-based portfolios
      is seldom analysed. AIM: To investigate whether students' reflections include
      sufficient dimensions of professional competence, notwithstanding a standardized
      portfolio format, and to evaluate students' satisfaction with the portfolio.
      METHODS: Thirty-five voluntary final-year medical students piloted a standardized
      portfolio in a general practice (GP) attachment at Lund University, Sweden.
      Students' portfolio reflections were based upon documentary evidence from
      practice, and aimed to demonstrate students' learning. The reflections were
      qualitatively analysed, using a framework approach. Students' evaluations of the
      portfolio were subjected to quantitative and qualitative analysis. RESULTS: Among
      professional issues, an integration of cognitive, affective and practical
      dimensions in clinical practice was provided by students' reflections. The
      findings suggested an emphasis on affective issues, particularly on self
      awareness of feelings, attitudes and concerns. In addition, ethical problems,
      clinical reasoning strategies and future communication skills training were
      subjects of several reflective commentaries. Students' reflections on their
      consultation skills demonstrated their endeavour to achieve structure in the
      medical interview by negotiation of an agenda for the consultation, keeping the
      interview on track, and using internal summarizing. The importance of active
      listening and exploration of patient's perspective was also emphasized. In
      students' case summaries, illustrating characteristic attributes of GP, the
      dominating theme was 'patient-centred care', including the patient-doctor
      relationship, holistic modelling and longitudinal continuity. Students were
      satisfied with the portfolio, but improved instructions were needed. CONCLUSIONS:
      A standardized portfolio in a defined course with a limited timeframe provided
      ample opportunities for reflections on professional issues. Support by mentors
      and a final examiner interview contributed to the success of the portfolio with
      students. The interview also allowed students to deepen their reflections and to
      receive feedback.

PMID- 21090941
TI  - A mandatory intercalated degree programme: revitalising and enhancing academic
      and evidence-based medicine.
AB  - BACKGROUND: Recruitment of medical graduates to research careers is declining.
      Expansion of medical knowledge necessitates all graduates be equipped to
      critically evaluate new information. To address these challenges, a mandatory
      intercalated degree programme was introduced as part of curriculum reform. AIMS:
      To review the place on intercalated degrees, the methods available for learning
      about research and to analyse experience with a new university programme focusing
      on research. METHODS: A literature review followed by the analysis of experience
      with eight cohorts of students who had completed the new programme. RESULTS: A
      total of 1599 students completed the programme. Laboratory-based research was the
      most common choice followed by clinical research, population health,
      epidemiology, medical humanities and mental health. Also, 93% of students spent
      over 75% of their time undertaking research. Sixty-three students published their
      research, half as first authors. Students and coordinators support the programme.
      Learning about research during the postgraduate phase is variable and frequently
      left to individual choice. CONCLUSION: Intercalating an additional degree
      focusing on research can achieve a number of learning objectives but demands a
      level of maturity, autonomy and preparedness, not uniformly present in students
      undertaking a mandatory intercalated programme. A more realistic goal is the
      development of 'research-mindedness' amongst all students.

PMID- 21090942
TI  - Introducing patient safety to undergraduate medical students--a pilot program
      delivered by health care administrators.
AB  - BACKGROUND: Identifying informed and interested staff to teach patient safety can
      be difficult. We report our experiences with a lecture-based program on patient
      safety delivered by health care administrators. METHOD: A self-administered
      questionnaire survey on patient safety culture was given to 130 third-year
      medical students before ('pre-test') and at 3 months after ('post-test') the
      program. The latter consisted of two 60-minute whole-class lectures using
      contemporary medical incidents in this locality as illustrative cases. RESULTS:
      Thirteen of the 23 questionnaire items (56.5%) showed statistically significant
      changes at the post-test. Students became more appreciative of the notions that
      errors were inevitable, and that disciplinary actions and 'being more careful'
      may not be the most effective strategies for the prevention of error. Issues
      concerning error reporting were more resistant to our educational intervention.
      Students regarded patient safety as an important topic that should be included in
      undergraduate teaching and professional examinations. CONCLUSION: The
      implementation of a patient safety curriculum should be tailored to an
      institution's needs, limitations, and culture. Health care administrators were
      found to be effective faculties. A brief lecture-based program could be
      integrated readily into an existing curriculum, and was found to produce at least
      short-term, positive changes.

PMID- 21090943
TI  - Triangulation of written assessments from patients, teachers and students: useful
      for students and teachers?
AB  - BACKGROUND: Many medical students in general practice clerkships experience lack
      of observation-based feedback. The StudentPEP project combined written feedback
      from patients, observing teachers and students. AIM: This study analyzes the
      perceived usefulness of triangulated written feedback. METHODS: A total of 71
      general practitioners and 79 medical students at the University of Oslo completed
      project evaluation forms after a 6-week clerkship. A principal component analysis
      was performed to find structures within the questionnaire. Regression analysis
      was performed regarding students' answers to whether StudentPEP was worthwhile.
      Free-text answers were analyzed qualitatively. RESULTS: Student and teacher
      responses were mixed within six subscales, with highest agreement on 'Teachers
      oral and written feedback' and 'Attitude to patient evaluation'. Fifty-four per
      cent of the students agreed that the triangulation gave concrete feedback on
      their weaknesses, and 59% valued the teachers' feedback provided. Two statements
      regarding the teacher's attitudes towards StudentPEP were significantly
      associated with the student's perception of worthwhileness. Qualitative analysis
      showed that patient evaluations were encouraging or distrusted. Some students
      thought that StudentPEP ensured observation and feedback. CONCLUSION: The patient
      evaluations increased the students' awareness of the patient perspective. A
      majority of the students considered the triangulated written feedback beneficial,
      although time-consuming. The teacher's attitudes strongly influenced how the
      students perceived the usefulness of StudentPEP.

PMID- 21090944
TI  - Addressing the systems-based practice requirement with health policy content and
      educational technology.
AB  - Duke University Hospital Office of Graduate Medical Education and Duke
      University's Fuqua School of Business collaborated to offer a Health Policy
      lecture series to residents and fellows across the institution, addressing the
      "Systems-based Practice" competency.During the first year, content was offered in
      two formats: live lecture and web/podcast. Participants could elect the modality
      which was most convenient for them. In Year Two, the format was changed so that
      all content was web/podcast and a quarterly live panel discussion was led by
      module presenters or content experts. Lecture evaluations, qualitative focus
      group feedback, and post-test data were analyzed.A total of 77 residents and
      fellows from 8 (of 12) Duke Graduate Medical Education departments participated.
      In the first year, post-test results were the same for those who attended the
      live lectures and those who participated via web/podcast. A greater number of
      individuals participated in Year Two. Participants from both years expressed the
      need for health policy content in their training programs. Participants in both
      years valued a hybrid format for content delivery, recognizing a desire for live
      interaction with the convenience of accessing web/podcasts at times and locations
      convenient for them. A positive unintended consequence of the project was
      participant networking with residents and fellows from other specialties.

PMID- 21090945
TI  - Therapeutic Patient Education: a new deal for medical education?

PMID- 21090946
TI  - Measuring the educational environment in health professions studies: a systematic
      review.
AB  - BACKGROUND: One of the determinants of the medical student's behaviour is the
      medical school learning environment. AIM: The aim of this research was to
      identify the instruments used to measure the educational environment in health
      professions education and to assess their validity and reliability. METHODS: We
      performed an electronic search in the medical literature analysis and retrieval
      system online (MEDLINE) and Timelit (Topics in medical education) databases
      through to October 2008. The non-electronic search (hand searching) was conducted
      through reviewing the references of the retrieved studies and identifying the
      relevant ones. Two independent authors read, rated and selected studies for the
      review according to the pre-specified criteria. The inter-rater agreement was
      measured with Kappa coefficient. RESULTS: Seventy-nine studies were included with
      the Kappa coefficient of 0.79, which demonstrated a reliable process, and 31
      instruments were extracted. The Dundee Ready Education Environment Measure,
      Postgraduate Hospital Educational Environment Measure, Clinical Learning
      Environment and Supervision and Dental Student Learning Environment Survey are
      likely to be the most suitable instruments for undergraduate medicine,
      postgraduate medicine, nursing and dental education, respectively. CONCLUSIONS:
      As a valid and reliable instrument is available for each educational setting, a
      study to assess the educational environment should become a part of an
      institution's good educational practice. Further studies employing a wider range
      of databases with more elaborated search strategies will increase the
      comprehensiveness of the systematic review.

PMID- 21090947
TI  - How to professionalise your practice as a health professions educator.

PMID- 21090948
TI  - Twelve Tips on usability testing to develop effective e-learning in medical
      education.
AB  - Usability testing is widely used in the commercial world during the process of
      developing new products, especially software and websites. However, it appears to
      be rarely used in the development of e-learning in medical education. The focus
      of usability testing is the user of the particular product and it informs product
      development by using a systematic process to identify usability problems at an
      early stage during product development so that these problems can be rectified.
      Usability testing of e-learning considers the characteristics of the learner, the
      technological aspects, the interaction and instructional design and finally the
      context. Testing under the conditions that the e-learning intervention will
      typically be used is the preferred method but more extreme situations can provide
      useful information. Product development should be iterative and rapid cycles of
      testing and refinement are essential to produce an effective e-learning
      intervention.

PMID- 21090949
TI  - Initial knowledge of medical professionalism among Chinese medical students.
AB  - BACKGROUND: Initial knowledge of professionalism among medical students is
      particularly important for designing effective professionalism curricula and for
      studying the change in the knowledge of professionalism. AIM: The study examined
      first-semester medical students' initial knowledge of important attributes of
      good doctors. METHODS: Mixed methods were used to examine initial knowledge among
      first-semester students from a Chinese medical college. We used an open-ended
      survey to identify attributes of good doctors and grounded theory analysis to
      find emergent themes. We also used a close-ended survey to solicit students'
      responses to 50 attributes of good doctors and explorative and confirmatory
      factor analysis to examine underlying factors. RESULTS: 973 students completed
      the open-ended survey while 1730 students completed the close-ended survey.
      Through grounded theory analysis, 24 subthemes and three themes that include
      Ethics, Skill, and Person, emerged from the data. Explorative and confirmatory
      factor analysis showed convergent results: 24 valid items and three factors that
      include Ethics, Skill, and Person were identified. CONCLUSION: The initial
      knowledge of medical professionalism among first-semester students involves
      approximately 24 important attributes within three major dimensions of Ethics,
      Skill, and Person, with an overwhelming emphasis on Ethics. It is neither
      sophisticated nor comprehensive, compared with specialists' professional
      knowledge.

PMID- 21090950
TI  - Medical students' use of Facebook to support learning: insights from four case
      studies.
AB  - BACKGROUND: Recent research indicates that university students are interested and
      active in supporting their learning by using Facebook, a popular social
      networking website. AIM: This study aimed to add to our understanding of how or
      how effectively students may be using Facebook for this purpose. METHOD:
      Researchers surveyed the extent and key features of Facebook use among 759
      medical students at one university, and explored in depth the design and conduct
      of four Facebook study groups. RESULTS: 25.5% of students reported using Facebook
      for education related reasons and another 50.0% said they were open to doing so.
      The case studies showed conservative approaches in students' efforts to support
      their development of medical knowledge, skills and attributes in this way. Both
      technological affordances and group dynamics were factors contributing to groups'
      mixed successes. CONCLUSION: These cases indicate that using Facebook as part of
      learning and teaching is as much of a challenge for many students as it may be
      for most educators.

PMID- 21090951
TI  - Enhancing medical students' conceptions of the CanMEDS Health Advocate Role
      through international service-learning and critical reflection: a
      phenomenological study.
AB  - BACKGROUND: Medical students are expressing increasing interest in international
      experiences in low-income countries where there are pronounced inequities in
      health and socio-economic development. AIM: We carried out a detailed exploration
      of the international service-learning (ISL) experience of three medical students
      and the value of critical reflection as a pedagogical approach to enhance medical
      students' conceptions of the Canadian Medical Education Directions for
      Specialists (CanMEDS) Health Advocate Role. METHOD: A phenomenological approach
      enabled us to study in considerable depth the students' experience from their
      perspective. Students kept reflective journals and wrote essays including
      detailed accounts of their experiences. The content of the students' journals and
      essays was analyzed using the critical incident technique. RESULTS: Students
      noted an increasingly meaningful sense of what it means to be vulnerable and
      marginalized, a heightened level of awareness of the social determinants of
      health and the related importance of community engagement, and a deeper
      appreciation of the health advocate role and key concepts embedded within it.
      CONCLUSION: This in-depth phenomenological study focused on the detailed
      experiences of three students from whom we learned that social justice-oriented
      approaches to service-learning, coupled with critical reflection, provide
      potentially viable pedagogical approaches for learning the health advocate role.
      How this experience will affect the students' future medical practice is yet
      unknown.

PMID- 21090952
TI  - Effect of the new Bologna bachelor degree on career considerations of medical
      students in one medical school.
AB  - BACKGROUND: The bachelor-master (BaMa) structure was introduced in medical
      schools in The Netherlands since 2003 and in Utrecht University in 2006. AIM: The
      aim of this study was to determine whether conferring a bachelor degree at the
      end of 3 years of medical school influences the career considerations of the
      students. METHODS: Two cohorts (BaMa and pre-BaMa) of medical students at Utrecht
      University were approached to fill out questionnaires in 2008 and 2009, about
      their career plans and whether a bachelor degree would affect these plans.
      RESULTS: In 2008, two-thirds of the students in both cohorts indicated that they
      considered a temporary stop. In 2009, the BaMa cohort showed substantially less
      interest in such a stop than the pre-BaMa cohort. Very few students considered a
      permanent stop. Comparison of third year pre-BaMa students (2008 cohort) with
      third year BaMa students (2009 cohort) revealed adjusted odds ratios of 2.34 (95%
      CI 1.34-4.09) for a temporary stop and 1.33 (95% CI 0.51-3.42) for a definitive
      stop. CONCLUSION: Awarding a bachelor degree in the BaMa structure does not
      encourage students to interrupt or discontinue their medical study, to transfer
      to another master programme or to transfer to another medical school.

PMID- 21090953
TI  - Determinants of successful deanship.
AB  - With the significant changes taking place in health and education as well as the
      rising demands and expectations, deans of medical faculties must exhibit strong
      and effective leadership skills. Deans need to focus on the broad scope and to
      translate their dreams into applied institutional operations and functions. It is
      thus necessary that the deans must identify the institution's core ideology, lead
      strategic planning, create a common vision and offer direction to the collective
      membership of the institution. Some personal qualities that appear to be critical
      for effective deanship include being visionary, fair, trustworthy and exemplary.
      Prospective deans should receive training in leadership. New deans must be
      properly informed on the strategic plan of the faculty before they are appointed.

PMID- 21090954
TI  - Techno-plagiarism.

PMID- 21090955
TI  - eMedical Teacher.

PMID- 21090958
TI  - Anxiety sensitivity and illicit sedative use among opiate-dependent women and
      men.
AB  - OBJECTIVES: Research has suggested that individuals with elevated anxiety
      sensitivity (AS) (the fear of benign bodily sensations associated with anxiety)
      are more likely to use substances to cope with distress, particularly substances
      with arousal-dampening effects such as benzodiazepines and other sedatives. Such
      coping motives may also vary as a function of gender, with women more likely to
      use substances for coping (self-medicating) purposes. Given these findings, we
      hypothesized that AS would be associated with illicit sedative use in an opioid
      dependent sample and that gender would moderate this relationship, with a greater
      association among women. METHOD: Participants were 68 opioid-dependent patients
      recruited from a methadone maintenance clinic. A logistic regression was used to
      determine whether AS was associated with presence or absence of a history of
      illicit sedative use. RESULTS: AS was significantly associated with sedative use
      and this relationship was moderated by gender; elevated AS was associated with
      greater sedative use only in women. CONCLUSION: The presence of elevated AS is
      related to greater illicit use of sedatives in women but not in men. Women may be
      more susceptible to seek sedatives as a means of coping with unpleasant, anxious
      sensations.

PMID- 21090959
TI  - Substance use and motivation: a longitudinal perspective.
AB  - BACKGROUND: Motivation to change substance use behavior is an important component
      of the recovery process that has usually been studied at entry into treatment.
      Less studied, but equally important, is the measurement of motivation over time
      and the role motivation plays in subsequent substance use. OBJECTIVES: The
      present study sought to examine longitudinal motivation toward sobriety among
      residents of sober living houses. METHODS: Sober living residents (n = 167) were
      followed at 6-month intervals over an 18-month period and assessed for motivation
      and substance use outcomes at each study interview. Motivation was measured using
      the costs and benefits subscales of the Alcohol and Drug Consequences
      Questionnaire (ADCQ) and substance use outcomes included the Addiction Severity
      Index (ASI) alcohol scale, ASI drug scale, and peak density of substance use
      (number of days of most use in a month). RESULTS: Participants reported higher
      benefits than costs of sobriety or cutting down substance use at every study time
      point. Using lagged generalized estimating equation models, the ADCQ costs
      predicted increased severity for alcohol, drugs, and peak density, whereas the
      benefits subscale predicted decreased drug and peak density. CONCLUSION:
      Longitudinal measurement of motivation can be a useful clinical tool to
      understand later substance use problems. SCIENTIFIC SIGNIFICANCE: Given the mixed
      findings from prior studies on the effects of baseline motivation, a shift toward
      examining longitudinal measures of motivation at proximal and temporal intervals
      is indicated.

PMID- 21090960
TI  - The impact of fatherhood on treatment response for men with co-occurring alcohol
      dependence and intimate partner violence.
AB  - OBJECTIVE: The role of fathers in the lives of children has gained increasing
      attention over the last several decades, however, studies that specifically
      examine the parenting role among men who are alcohol dependent and have co
      occurring intimate partner violence (IPV) have been limited. This brief report is
      intended to highlight the need to develop and focus interventions for men with co
      occurring substance abuse and IPV with an emphasis on their roles as fathers.
      METHOD: Sixty-nine men who participated in a randomized comparison study of a
      coordinated substance abuse and domestic violence treatment program (SADV) and
      Twelve Step Facilitation (TSF) provided information about whether they were
      fathers. Analysis of covariance was used to assess the impact of fatherhood on
      the outcomes of intimate partner violence and alcohol use during the 12 weeks of
      treatment. RESULTS: There was a significant interaction between type of treatment
      (SADV vs. TSF) and fatherhood. SADV resulted in significantly less IPV and use of
      alcohol over the 12 weeks of treatment than TSF for men without children. There
      were no significant differences between SADV and TSF for men who were fathers.
      CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Results indicate a need to further
      explore the role of fatherhood for men with co-occurring substance abuse and IPV
      and development of specialized treatments that may improve treatment outcomes for
      fathers.

PMID- 21090961
TI  - HIV infection, inflammation, immunosenescence, and aging.
AB  - Although antiretroviral therapy for HIV infection prevents AIDS-related
      complications and prolongs life, it does not fully restore health. Long-term
      treated patients remain at higher than expected risk for a number of
      complications typically associated with aging, including cardiovascular disease,
      cancer, osteoporosis, and other end-organ diseases. The potential effect of HIV
      on health is perhaps most clearly exhibited by a number of immunologic
      abnormalities that persist despite effective suppression of HIV replication.
      These changes are consistent with some of the changes to the adaptive immune
      system that are seen in the very old ("immunosenescence") and that are likely
      related in part to persistent inflammation. HIV-associated inflammation and
      immunosenescence have been implicated as causally related to the premature onset
      of other end-organ diseases. Novel therapeutic strategies aimed at preventing or
      reversing these immunologic defects may be necessary if HIV-infected patients are
      to achieve normal life span.

PMID- 21090963
TI  - The Fabry cardiomyopathy: models for the cardiologist.
AB  - Fabry disease is an X-linked lysosomal storage disorder caused by alpha
      galactosidase A deficiency. Intracellular accumulation of globotriaosylceramide
      starts in utero and progressively develops in various tissues and organs. Cardiac
      involvement is frequent, and its presentation as concentric nonobstructive left
      ventricular hypertrophy serves as a model for other hypertrophic
      cardiomyopathies. This review describes the Fabry cardiomyopathy, its treatment,
      and multidisciplinary patient care models. These models will help clinicians in
      diagnosing, assessing, and treating patients with Fabry disease. As the models
      can be extrapolated to other diseases, they might contribute to more optimal
      clinical management of patients with other cardiac disorders.

PMID- 21090962
TI  - The brain-gut axis in abdominal pain syndromes.
AB  - The importance of bidirectional brain-gut interactions in gastrointestinal (GI)
      illness is increasingly recognized, most prominently in the area of functional GI
      syndromes such as irritable bowel syndrome (IBS), functional dyspepsia, and
      functional chest pain. The brain receives a constant stream of interoceptive
      input from the GI tract, integrates this information with other interoceptive
      information from the body and with contextual information from the environment,
      and sends an integrated response back to various target cells within the GI
      tract. This system is optimized to assure homeostasis of the GI tract during
      physiological perturbations and to adapt GI function to the overall state of the
      organism. In health, the great majority of interoceptive information reaching the
      brain is not consciously perceived but serves primarily as input to autonomic
      reflex pathways. In patients with functional abdominal pain syndromes, conscious
      perception of interoceptive information from the GI tract, or recall of
      interoceptive memories of such input, can occur in the form of constant or
      recurrent discomfort or pain. This is often associated with alterations in
      autonomic nervous system output and with emotional changes. A model is proposed
      that incorporates reported peripheral and central abnormalities in patients with
      IBS, extrapolates similar alterations in brain-gut interactions to patients with
      other chronic abdominal pain syndromes, and provides novel treatment targets.

PMID- 21090965
TI  - Multiple myeloma.
AB  - Multiple myeloma (MM) is a B cell neoplasm of the bone marrow with a complex
      array of clinical manifestations including anemia, bone lesions, hypercalcemia,
      renal dysfunction, and compromised immune function. It accounts for 10%-15% of
      all hematologic malignancies, and 20% of deaths related to cancers of the blood
      and bone marrow. The diagnosis of MM is based on the presence of neoplastic
      plasma cells in the bone marrow or other extramedullary sites, along with
      evidence of disease-related organ dysfunction. Although the disease remains
      incurable, significant advances in both basic and translational research have
      enhanced understanding of disease pathogenesis and guided the development of new
      and more effective therapies. These agents include the immunomodulatory drugs
      thalidomide and lenalidomide, the proteasome inhibitor bortezomib, and other
      therapeutics that are currently being evaluated. This review highlights important
      historical landmarks in the field of MM, examines the pathogenesis and clinical
      manifestations of the disease, and outlines principles of both diagnosis and
      treatment of MM.

PMID- 21090966
TI  - Dynamics of nanoconfined supercooled liquids.
AB  - Near their glass transition temperature T(g), supercooled liquids display
      dramatic changes regarding the dynamics if subject to geometrical restrictions on
      the scale of 2 to 200 nm. Confinement-induced shifts of T(g) of 25 K have been
      reported, equivalent to relaxation times that differ by several orders of
      magnitude compared with the bulk liquid at the same temperature. Both
      acceleration and frustration of structural relaxations have been observed, and
      the effects can depend strongly on the physical and chemical properties of the
      interface, on soft versus hard confinement, and on the size and dimensionality of
      the confining topology. This review attempts to extract a unifying picture from
      the past 20 years of diverse observations that involve experiments, simulations,
      and model considerations.

PMID- 21090964
TI  - Toward fulfilling the promise of molecular medicine in fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common inherited form of mental retardation
      and a leading known cause of autism. It is caused by loss of expression of the
      fragile X mental retardation protein (FMRP), an RNA-binding protein that
      negatively regulates protein synthesis. In neurons, multiple lines of evidence
      suggest that protein synthesis at synapses is triggered by activation of group 1
      metabotropic glutamate receptors (Gp1 mGluRs) and that many functional
      consequences of activating these receptors are altered in the absence of FMRP.
      These observations have led to the theory that exaggerated protein synthesis
      downstream of Gp1 mGluRs is a core pathogenic mechanism in FXS. This excess can
      be corrected by reducing signaling by Gp1 mGluRs, and numerous studies have shown
      that inhibition of mGluR5, in particular, can ameliorate multiple mutant
      phenotypes in animal models of FXS. Clinical trials based on this therapeutic
      strategy are currently under way. FXS is therefore poised to be the first
      neurobehavioral disorder in which corrective treatments have been developed from
      the bottom up: from gene identification to pathophysiology in animals to novel
      therapeutics in humans. The insights gained from FXS and other autism-related
      single-gene disorders may also assist in identifying molecular mechanisms and
      potential treatment approaches for idiopathic autism.

PMID- 21090967
TI  - Interaction of cigarette exposure and airway epithelial cell gene expression.
AB  - Cigarette smoking is responsible for lung cancer and chronic obstructive
      pulmonary disease (COPD), the leading cause of death from cancer and the second
      leading cause of death in the United States. In the United States, 46 million
      people smoke, with an equal number of former smokers. Moreover, 20-25% of current
      or former smokers will develop either disease, and smokers with one disease are
      at increased risk for developing the other. There are no tools for predicting
      risk of developing either disease; no accepted tools for early diagnosis of
      potentially curable lung cancer; and no tools for defining molecular pathways or
      molecular subtypes of these diseases, for predicting rate of progression, or for
      assessing response to therapy at a biochemical or molecular level. This review
      discusses current studies and the future potential of measuring global gene
      expression in epithelial cells that are in the airway field of injury and of
      using the genomic information derived to begin to answer some of the above
      questions.

PMID- 21090968
TI  - The pathogenesis of systemic sclerosis.
AB  - Systemic sclerosis (SSc), also known as scleroderma, is a rare connective tissue
      disease characterized by vascular and immune dysfunction, leading to fibrosis
      that can damage multiple organs. Its pathogenesis is complex and poorly
      understood. Two major clinical subtypes are the limited and diffuse forms.
      Research into SSc has been hampered by its rarity, its clinical heterogeneity,
      and the lack of mouse models that accurately recapitulate the disease. Clinical
      and basic studies have yielded some mechanistic clues regarding pathogenesis.
      Recent insights gained through the use of microarrays have revealed distinctive
      subsets of SSc within and beyond the limited and diffuse subsets. In this review,
      we discuss potential mechanisms underlying the vascular, autoimmune, and fibrotic
      points of dysregulation. Proper categorization of SSc patients for research
      studies by use of microarrays or other biomarkers is critical, as disease
      heterogeneity may explain some of the inconsistencies of prior studies.

PMID- 21090969
TI  - Molecular genetics of colorectal cancer.
AB  - Over the past three decades, molecular genetic studies have revealed some
      critical mutations underlying the pathogenesis of the sporadic and inherited
      forms of colorectal cancer (CRC). A relatively limited number of oncogenes and
      tumor-suppressor genes-most prominently the APC, KRAS, and p53 genes-are mutated
      in a sizeable fraction of CRCs, and a larger collection of genes that are mutated
      in subsets of CRC have begun to be defined. Together with DNA-methylation and
      chromatin-structure changes, the mutations act to dysregulate conserved signaling
      networks that exert context-dependent effects on critical cell phenotypes,
      including the regulation of cellular metabolism, proliferation, differentiation,
      and survival. Much work remains to be done to fully understand the nature and
      significance of the individual and collective genetic and epigenetic defects in
      CRC. Some key concepts for the field have emerged, two of which are emphasized in
      this review. Specifically, the gene defects in CRC often target proteins and
      pathways that exert pleiotropic effects on the cancer cell phenotype, and
      particular genetic and epigenetic alterations are linked to biologically and
      clinically distinct subsets of CRC.

PMID- 21090986
TI  - Adherence to optimal lifestyle behaviors is related to emotional health
      indicators among employees.
AB  - Simultaneous adherence to abstinence from smoking, adequate physical activity,
      eating 5 servings of fruits and vegetables each day, and consuming limited or no
      amount of alcohol has been associated with a variety of health outcomes, but not
      emotional health. The purpose of this investigation was to study the association
      between optimal lifestyle behaviors and self-reported emotional health indicators
      among employed adults. Emotional health indicators studied were feeling
      depressed, stress risk, and the impact of emotional health on daily life among
      employees (N = 34,603). Binary logistic regression models were used to predict
      likelihood of feeling depressed and risk of stress based on degree of adherence
      to optimal lifestyle. Multinomial logistic regression models were used to assess
      the association between adherence to optimal lifestyle and likelihood of
      emotional quality of life among employees. Analyses were adjusted for age, sex,
      socioeconomic status (using the area deprivation index), sleep, self-perceived
      health status, self-efficacy, and chronic conditions including depression. All
      data were self-reported except for the area deprivation index. Adherence to any 3
      or 4 components of the optimal lifestyle was associated with all 3 emotional
      health issues studied: Lower odds of feeling depressed, reporting stress risk,
      and emotional health affecting daily life. Adherence to any 2 components of the
      optimal lifestyle metric was associated with lower odds of feeling depressed and
      emotional health affecting daily life. All 4 individual lifestyle behaviors had
      significant associations with at least 2 of the 3 emotional health outcomes
      studied. Adherence to optimal lifestyle is associated with significantly more
      positive emotional health states as measured by feeling depressed, risk for high
      stress, and impact of emotional health on daily life. While causality cannot be
      inferred, the strength of the associations warrants trials to determine the
      extent to which adopting positive lifestyles can result in improved mental
      health.

PMID- 21090987
TI  - The association between optimal lifestyle adherence and short-term incidence of
      chronic conditions among employees.
AB  - "Optimal lifestyle," comprising abstinence from smoking, adequate physical
      activity, eating 5 servings of fruits and vegetables each day, and consuming
      limited or no alcohol, is associated with low risk of chronic disease when
      unselected populations are observed for long periods of time. It is unclear
      whether these same associations are present when observation is limited to
      employed individuals followed for a brief period of time. The purpose of this
      investigation was to study the association between adherence to optimal lifestyle
      and the incidence of chronic conditions among employees over a 2-year period.
      Logistic regression was used to assess the association between employees' (N  =
      6848) adherence to optimal lifestyle and the incidence of diabetes, heart
      disease, cancer, hypertension, high cholesterol, and back pain during a 2-year
      period. All data were self-reported. Adherence to any 3 components of the optimal
      lifestyle was associated with a significantly lower near-term incidence of
      diabetes (odds ratio [OR] =  0.56; 95% confidence interval [CI] = 0.31-0.97) and
      back pain (OR = 0.69; 95% CI = 0.53-0.92). Adherence to all 4 optimal lifestyle
      components was significantly associated with lower near-term incidence of back
      pain (OR = 0.44; 95% CI = 0.26-0.76). Physical activity was associated with
      significantly lower near-term incidence risk of heart disease (OR = 0.60; 95% CI
      = 0.38-0.95), high cholesterol (OR = 0.80; 95% CI = 0.66-0.99), and diabetes (OR
      = 0.51; 95% CI = 0.30-0.86). Adherence to optimal lifestyle, in particular
      adequate physical activity, is associated with lower near-term risk of developing
      several chronic conditions. Employers and payers should consider this fact when
      formulating policy or allocating resources for health care and health promotion.

PMID- 21090988
TI  - Multifocal vulvar smooth muscle tumor with an unusual intravascular growth
      pattern and multiple local recurrences in a 10-year-old child: a diagnostic
      dilemma.
AB  - Smooth muscle tumors of the vulva are rare entities with variable morphologic
      features and clinical behavior. Our report summarizes the case of a multifocal
      vulvar smooth muscle tumor of undetermined malignant potential with an unusual
      intravascular growth pattern and subsequent local recurrence in a 10-year-old
      girl, the youngest case reported to date, and reviews the specific pathologic
      findings of that category. Vulvar smooth muscle tumors of undetermined malignant
      potential represent a diagnostic, prognostic, and therapeutic challenge. The
      histologic features of this case were predictive of local recurrence, although
      the significance of the intravascular growth pattern is still uncertain. The
      relationship of this multifocal, recurrent tumor to the clinical entity, vulvar
      leiomyomatosis, is unknown at this time.

PMID- 21090989
TI  - A case study of early experience with implementation of collaborative care in the
      Veterans Health Administration.
AB  - Primary care remains critically important for those who suffer from mental
      disorders. Although collaborative care, which integrates mental health services
      into primary care, has been shown to be more effective than usual care, its
      implementation has been slow and the experience of providers and patients with
      collaborative care is less well known. The objective of this case study was to
      examine the effects of collaborative care on patient and primary care provider
      (PCP) experiences and communication during clinical encounters. Participating
      physicians completed a self-administered visit reconstruction questionnaire in
      which they logged details of patient visits and described their perceptions of
      the visits and the influence of collaborative care. Audio recordings of visits
      were analyzed to assess the extent of discussion about colocated mental health
      services and visit time devoted to mental health topics. The main outcome
      measures were the extent of discussion and recommendation for collaborative care
      during clinical visits and providers' experiences based on their responses to the
      visit reconstruction questionnaire. Providers surveyed expressed enthusiasm about
      collaborative care and cited the time constraint of office visits and lack of
      specialty support as the main reasons for limiting their discussion of mental
      health topics with patients. Despite the availability of mental health providers
      at the same clinic, PCPs missed many opportunities to address mental health
      issues with their patients. Ongoing education for PCPs regarding how to conduct a
      "warm handoff" to colocated providers will need to be an integral part of the
      implementation of collaborative care.

PMID- 21090990
TI  - Ectopic expression of single transcription factors directs differentiation of a
      medaka spermatogonial cell line.
AB  - The capability to form all cell types of the body is a unique feature of stem
      cells. However, many questions remain concerning the mechanisms regulating
      differentiation potential. The derivation of spermatogonial cell lines (SGs) from
      mouse and human, which can differentiate across germ-layer borders, suggested
      male germ cells as a potential stem cell source in addition to embryonic stem
      cells. Here, we present a differentiation system using an SG of the vertebrate
      model organism Oryzias latipes (medaka). We report differentiation of this cell
      line into 4 different ectodermal and mesodermal somatic cell types. In addition
      to differentiation into adipocytes by retinoic acid treatment, we demonstrate for
      the first time that directed differentiation of an SG can be induced by ectopic
      expression of single transcription factors, completely independent of culture
      conditions. Transient transfection with mitf-m, a transcription factor that has
      been shown to induce differentiation into melanocytes in medaka embryonic stem
      cells, resulted in the formation of the same cell type in spermatogonia.
      Similarly, the formation of neuron-like cells and matrix-depositing osteoblasts
      was induced by ectopic expression of mash1 and cbfa1, respectively.
      Interestingly, we found that the expression of all mentioned fate-inducing
      transcription factors leads to recapitulation of the temporal pattern of marker
      gene expression known from in vivo studies.

PMID- 21090991
TI  - The impact of postdischarge telephonic follow-up on hospital readmissions.
AB  - Abstract Recurrent hospitalizations are responsible for considerable health care
      spending, although prior studies have shown that a substantial proportion of
      readmissions are preventable through effective discharge planning and patient
      follow-up after the initial hospital visit. This retrospective cohort study was
      undertaken to determine whether telephonic outreach to ensure patient
      understanding of and adherence to discharge orders following a hospitalization is
      effective at reducing hospital readmissions within 30 days after discharge.
      Claims data were analyzed from 30,272 members of a commercial health plan who
      were discharged from a hospital in 2008 to determine the impact of telephonic
      intervention on the reduction of 30-day readmissions. Members who received a
      telephone call within 14 days of discharge and were not readmitted prior to that
      call comprised the intervention group; all other members formed the comparison
      group. Multiple logistic regression was used to determine the impact of the
      intervention on 30-day readmissions, after adjusting for covariates. Results
      demonstrated that older age, male sex, and increased initial hospitalization
      length of stay were associated with an increased likelihood of readmission (P <
      0.001). Receipt of a discharge call was associated with reduced rates of
      readmission; intervention group members were 23.1% less likely than the
      comparison group to be readmitted within 30 days of hospital discharge (P =
      0.043). These findings indicate that timely discharge follow-up by telephone to
      supplement standard care is effective at reducing near-term hospital readmissions
      and, thus, provides a means of reducing costs for health plans and their members.

PMID- 21090992
TI  - Eco-evolutionary metapopulation dynamics and the spatial scale of adaptation.
AB  - We construct a model that combines extinction-colonization dynamics with the
      dynamics of local adaptation in a network of habitat patches of dissimilar
      qualities. We derive a deterministic approximation for the stochastic model that
      allows the calculation of patch-specific incidences of occupancy and levels of
      adaptation at steady state. Depending on (i) the strength of local selection,
      (ii) the amount of genetic variance, (iii) the demographic cost of maladaptation,
      (iv) the spatial scale of gene flow, and (v) the amount of habitat heterogeneity,
      the model predicts adaptation at different spatial scales. Local adaptation is
      predicted when there is much genetic variance and strong selection, while network
      level adaptation occurs when the demographic cost of maladaptation is low. For
      little genetic variance and high cost of maladaptation, the model predicts
      network-level habitat specialization in species with long-range migration but an
      intermediate scale of adaptation (mosaic specialization) in species with short
      range migration. In fragmented landscapes, the evolutionary dynamics of
      adaptation may both decrease and enhance metapopulation viability in comparison
      with no evolution. The model can be applied to real patch networks with given
      sizes, qualities, and spatial positions of habitat patches.

PMID- 21090993
TI  - Is the F(ST) a good predictor of extinction?
AB  - The organization of neutral genetic variation has long been used as a diagnostic
      tool to infer demographic properties of populations, and recently it has been
      shown that this information can also be used to estimate the magnitude of genetic
      deterioration in small or fragmented populations. A further step of this research
      is to assess whether neutral genetic indicators can serve to predict and compare
      the viabilities of endangered species. I use modeling to explore how ecological
      metapopulation settings are related to neutral genetic indicators (such as the
      fixation index [F(ST)]), changes in genetic load, and metapopulation viability.
      The analysis indicates that genetic indicators are generally strongly and
      consistently correlated with the genetic load, population size and structure, and
      time of extinction but identifies two potential limitations for their use in
      viability assessments. First, the regime of environmental perturbations is not
      accurately reflected by neutral indicators, so that their predictive power may be
      reduced in variable environments. Second, many species are threatened by recent
      human-induced changes of their habitat configuration. In most cases, genetic
      indicators may not have reached their equilibrium value in the altered habitat,
      which limits their ability to compare species with heterogeneous histories and
      life-history traits.

PMID- 21090995
TI  - Current state of in vivo confocal microscopy in management of microbial
      keratitis.
AB  - PURPOSE: The purpose of this study was to review the current literature on in
      vivo confocal microscopy of the cornea and to discuss the current clinical
      indications for its use in microbial keratitis. METHODS: Review of select recent
      literature on in vivo confocal microscopy and atypical microbial keratitis.
      RESULTS: Delayed diagnosis of Acanthamoeba and fungal keratitis is typical,
      resulting in significant vision loss. This is partially due to the low
      sensitivity and time delay of corneal cultures. In the hands of an experienced
      viewer, the confocal microscope has been found to have a sensitivity of up to 90%
      in the diagnosis of Acanthamoeba keratitis and close to 80% for fungal keratitis.
      CONCLUSION: In vivo confocal microscopy is emerging as a tool for rapid diagnoses
      in severe infectious keratitis with high sensitivity. In addition, it can be used
      to monitor treatment response, allowing guidance to clinicians for medical or
      surgical management.

PMID- 21090996
TI  - In vivo confocal microscopy of corneal nerves: analysis and clinical correlation.
AB  - Corneal confocal microscopy is a growing technique for the study of the cornea at
      the cellular level, providing images comparable to ex vivo histochemical methods.
      In vivo confocal microscopy (IVCM) has an enormous potential, being a noninvasive
      procedure that images the living cornea, to study both its physiological and
      pathological states. Corneal nerves are of great interest to clinicians and
      scientists due to their important roles in regulating corneal sensation,
      epithelial integrity, proliferation, wound healing, and for their protective
      functions. IVCM enables the noninvasive examination of corneal nerves, allowing
      the study of nerve alterations in different ocular diseases, after corneal
      surgery, and in systemic diseases. To date, the correlation of sub-basal corneal
      nerves and their function has been studied in normal eyes, keratoconus, dry eye,
      contact lens wearers, and in neurotrophic keratopathy, among others. Further, the
      effect of corneal surgery on nerves has been studied, demonstrating the
      regenerative capacity of corneal nerves and the recovery of sensation. Moreover,
      IVCM has been applied in the diagnosis of peripheral diabetic neuropathy and the
      assessment of progression in this systemic disease. The purpose of this review is
      to describe the principles, applications, and clinical correlation of IVCM in the
      study of corneal nerves in different ocular and systemic diseases.

PMID- 21090998
TI  - In vivo high-resolution retinal imaging using adaptive optics.
AB  - Retinal imaging with conventional methods is only able to overcome the lowest
      order of aberration, defocus and astigmatism. The human eye is fraught with
      higher order of aberrations. Since we are forced to use the human optical system
      in retinal imaging, the images are degraded. In addition, all of these
      distortions are constantly changing due to head/eye movement and change in
      accommodation. Adaptive optics is a promising technology introduced in the field
      of ophthalmology to measure and compensate for these aberrations. High-resolution
      obtained by adaptive optics enables us to view and image the retinal
      photoreceptors, retina pigment epithelium, and identification of cone subclasses
      in vivo. In this review we will be discussing the basic technology of adaptive
      optics and hardware requirement in addition to clinical applications of such
      technology.

PMID- 21090997
TI  - In vivo imaging of corneal inflammation: new tools for clinical practice and
      research.
AB  - PURPOSE: Infectious and inflammatory corneal diseases are a major cause of
      blindness. To date, assessment of corneal inflammation, has only been possible by
      slit-lamp biomicroscopy. The purpose of this study is to review the current state
      of imaging technologies enabling in vivo imaging of inflammation in the cornea.
      METHODS: Literature review of peer-reviewed articles on in vivo imaging
      modalities. RESULTS: Current means of diagnosis and treatment follow-up for
      immune and infectious keratitis are limited to slit-lamp biomicroscopy. Several
      modalities are currently emerging, allowing for in vivo imaging of corneal
      inflammation, including in vivo confocal microscopy, anterior segment optical
      coherence tomography, and intravital multiphoton microscopy. CONCLUSION: Several
      in vivo imaging technologies are currently evolving, allowing for objective
      assessment of corneal inflammation and treatment response.

PMID- 21090999
TI  - Ocular coherence tomography and diabetic eye disease.
AB  - Optical Coherence Tomography (OCT) is a high-resolution, cross-sectional imaging
      technique that allows detailed assessment of retinal thickness and morphologic
      evaluation of the neurosensory retinal layers. OCT imaging has rapidly been
      integrated into diagnosis and management of diabetic macular edema (DME) in
      routine clinical practice and clinical trials. OCT findings correlate well with
      other evaluation techniques for DME. Although there is a moderate correlation
      between OCT measured retinal thickness and visual acuity, OCT cannot replace
      visual acuity because there is a high degree of variability. Recent improvements
      in OCT technology have led to widespread interest in the use of spectral domain
      OCT, which is faster and has higher resolution than time domain OCT. Future
      research in OCT imaging will likely result in improvements in image quality. The
      ability to combine OCT with other various diagnostic modalities will further
      improve the evaluation of DME in both clinical practice and trials.

PMID- 21091000
TI  - Use of optical coherence tomography to evaluate papilledema and
      pseudopapilledema.
AB  - Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, describes a
      condition of elevated intracranial pressure (ICP) that typically presents in
      obese women of childbearing age with symptoms and signs of posture-dependent
      headaches, pulsatile tinnitus, visual changes, and papilledema. Optical coherence
      tomography (OCT) has begun to be utilized as an adjunctive, quantitative tool in
      the evaluation of patients with IIH to help distinguish between true optic nerve
      head edema and pseudopapilledema, and to contribute to our understanding of the
      consequences of prolonged optic nerve edema. Although few longitudinal studies of
      patients with IIH have been published to date, it appears that there may be a
      correlation between retinal nerve fiber layer (RNFL) thickness and visual
      function. With the new spectral domain OCT, additional parameters of the optic
      nerve imaging, including volume and height measurements, might provide greater
      sensitivity of the response to treatment and the long-term visual outcome in
      patients with IIH.

PMID- 21091001
TI  - Fundus autofluorescence in geographic atrophy: a review.
AB  - Fundus autofluorescence is a noninvasive imaging technology that provides
      information on the distribution of lipofuscin within the retinal pigment
      epithelial cell monolayer. Progressive accumulation of lipofuscin within retinal
      pigment epithelial cells is involved in the pathogenesis of geographic atrophy in
      age-related macular degeneration. This review contains an introduction to fundus
      autofluorescence, review of currently available imaging methods, and discussion
      of the role of autofluorescence imaging in geographic atrophy progression. The
      recent classification of geographic atrophy phenotypes by the Fundus
      Autofluorescence in Age-related Macular Degeneration Study (FAM) and the
      association of phenotype and atrophy progression are also summarized.

PMID- 21091002
TI  - Review of the use of digital imaging in retinopathy of prematurity screening.
AB  - Retinopathy of prematurity (ROP) is a vision-threatening vasoproliferative
      condition of premature infants worldwide. As survival rates of younger and
      smaller infants improve, more babies are at risk for the development of ROP and
      blindness. Meanwhile, fewer ophthalmologists are available for bedside indirect
      ophthalmoscopy screening examinations. Remote digital imaging is a promising
      method with which to identify those infants with treatment-requiring or referral
      warranted ROP quickly and accurately, and may help circumvent issues regarding
      the limited availability of ROP screening providers. The Retcam imaging system is
      the most common system for fundus photography, with which high-quality
      photographs can be obtained by trained non-physician personnel and evaluated by a
      remote expert. It has been shown to have high reliability and accuracy in
      detecting referral-warranted ROP, particularly at later postmenstrual ages.
      Additionally, the method is generally well received by parents and is highly cost
      effective.

PMID- 21091003
TI  - Ocular telemedicine for diabetic retinopathy and the Joslin Vision Network.
AB  - Diabetic retinopathy (DR) is the most common microvascular complication of
      diabetes. The Joslin Vision Network Diabetes Eye Care Program (JVN) is a
      validated ocular telemedicine program developed at the Joslin Diabetes Center
      that has provided diabetes eye care to over 70,000 persons. The JVN allows
      accurate assessment of level of DR severity, detects the presence of nondiabetic
      eye disease, and allows determination of appropriate treatment recommendations.
      The JVN integrates eye care in a comprehensive diabetes program, extends access
      to evidence-based diabetes eye care, and offers alternative means of diabetes eye
      care in appropriate settings, ultimately preserving vision and preventing visual
      loss.

PMID- 21091004
TI  - The use of diffusion MRI in ischemic optic neuropathy and optic neuritis.
AB  - Ischemic optic neuropathy and optic neuritis are the most common causes of
      unilateral non-glaucomatous visual loss. While they have distinctive clinical
      features, they also share some overlapping profiles that make it difficult to
      clinically distinguish these two entities. MRI with gadolinium has been proven to
      be helpful to confirm the diagnosis of optic neuritis, but ischemic optic
      neuropathy remains a clinical diagnosis. Diffusion MRI, a newly advanced
      technique, has been used in studying the pathophysiology of optic neuritis, but
      its use in ischemic optic neuropathy is limited. Diffuse MRI may potentially be
      of help to diagnose ischemic optic neuropathy.

PMID- 21091005
TI  - Technological advances shaping scleral lenses: the Boston ocular surface
      prosthesis in patients with glaucoma tubes and trabeculectomies.
AB  - The Boston Ocular Surface Prosthesis (BOS-P) (Boston Foundation for Sight,
      Needham, MA) is a fluid-ventilated rigid gas-permeable scleral lens that is
      utilized for the treatment of irregular corneal astigmatism and severe ocular
      surface disease. Recent reports have highlighted the utility of the BOS-P as a
      therapeutic device in cases of persistent epithelial defects, corneal
      neovascularization, ocular graft versus host disease, and exposure keratopathy.
      Patients with significant cornea disease might also have glaucoma, and those who
      have undergone glaucoma surgery, which typically disrupts the limbus, present a
      challenge when fitting the BOS-P. This report describes five patients with a
      history of both corneal disease and glaucoma surgery who were successfully fitted
      with the BOS-P.

PMID- 21091006
TI  - Expanding application of the Boston type I keratoprosthesis due to advances in
      design and improved post-operative therapeutic strategies.
AB  - PURPOSE: To evaluate how the advances in design of the Boston type I
      keratoprosthesis and in the treatment strategies to conquer the post operative
      complications have expanded the indications and application of this technology.
      METHODS: A review and analysis of the keratoprosthesis literature specifically
      examining design modifications, treatment of post operative complications, and
      patient selection was performed. RESULTS: Over the past two decades, many
      modifications to the design of the Boston type I keratoprosthesis and treatment
      of the patient in the post operative period have occurred. Also, the technology
      has been more widely accepted as a primary surgical option for patients with a
      poor preoperative prognosis for traditional penetrating keratoplasty. The
      outcomes of visual acuity, retention, and post-operative infection rates have all
      significantly improved since the technology has been modified and offers patients
      an alternative for visual rehabilitation. CONCLUSIONS: Thanks to advances in
      design and perioperative care, the boston type i keratoprosthesis can now be
      considered a viable option for surgical visual rehabilitation in many patients
      with corneal pathology, and in certain groups the primary surgical procedure of
      choice.

PMID- 21091007
TI  - Keratoprosthesis: procedure of choice for corneal opacities in children?
AB  - PURPOSE: The purpose of this study is to review the current literature on
      keratoprosthesis and its use in the pediatric population. METHODS: Case report
      and review of recent literature on outcomes of pediatric keratoplasty and
      keratoprosthesis. RESULTS: Penetrating keratoplasty in children is fraught with
      shortcomings, including difficulty maintaining a clear graft (as low as 44% at 50
      months), poor visual acuity outcomes (only 30-34% achieving 20/400 or better),
      and a high rate of allograft rejection (40-50%). Placement of the Boston type I
      keratoprosthesis has the advantage of achieving a clear visual axis and stable
      refractive error within days of surgery without risk of rejection. However, life
      long care is required, including topical steroids and antibiotic prophylaxis, as
      well as bandage contact lens wear and a frequent a need for further interventions
      for retroprosthetic membranes and glaucoma. CONCLUSIONS: With motivated parents,
      a successful anatomic and functional outcome can be achieved with the Boston
      keratoprosthesis in children of amblyogenic age.

PMID- 21091008
TI  - Corneal cross linking for keratoconus.
AB  - Riboflavin-induced ultraviolet light (UV) cross linking has received a
      significant amount of attention in recent years. It is currently approved in
      Europe as a treatment for keratoconus and is also being used for other corneal
      disorders. The goal of this paper is to review in detail seminal papers and
      studies that have been done to support cross linking as a safe and effective
      treatment for patients with early stages of keratoconus.

PMID- 21091009
TI  - Alternative applications of the femtosecond laser in ophthalmology.
AB  - PURPOSE: To provide an update of novel applications for the femtosecond (FS)
      laser in ophthalmology. DESIGN: Perspective, literature review, case report, and
      commentary. METHODS: Literature review. RESULTS: The many advantages of etching
      flaps with the FS laser for laser in situ keratomileusis (LASIK) have been well
      established. Alternative applications of the FS have been approved and are now
      used in clinical practice. In refractive ophthalmology, the FS laser can be used
      for lenticule extraction to correct myopia and intrastromal biochemical
      manipulation to correct presbyopia. This laser can be used for preparing host and
      donor tissue for both full thickness and lamellar keratoplasty. Research is
      underway, exploring ways to employ the FS laser for different stages of cataract
      surgery. Cosmetic procedures with FS-assisted tattooing serve to correct
      leukoria. CONCLUSIONS: Advancements in technology have allowed measurable
      improvements in the surgical safety, efficiency, speed, and versatility of FS
      lasers in ophthalmology.

PMID- 21091010
TI  - Glaucoma drainage devices: a review of the past, present, and future.
AB  - Glaucoma drainage devices are more frequently being used for glaucoma filtering
      surgeries, even those at low risk for failure with trabeculectomy. There are 4
      major devices available: the Molteno, Baerveldt, Krupin, and Ahmed. The Molteno
      and Baerveldt are non-valved implants, while the Krupin and Ahmed are valved. The
      success rates of the different valves are about equal at approximately 70% with a
      mean intraocular pressure (IOP) lowering of at least 50% from the pre-operative
      IOP. Unfortunately, the failure rate is about 10% per year, leading to only 50%
      functional drainage devices at 5 years. Therefore, research on the biomaterials,
      shape, and technique of drainage implant surgery is being done in hopes of
      increasing long term success rates.

PMID- 21091011
TI  - Technological advances in pediatric cataract surgery.
AB  - PURPOSE: Managing pediatric cataracts is often challenging. It is technically
      difficult to perform surgery in these small complaint eyes and there is higher
      prevalence of postoperative complications. The outcomes of surgery depend on
      technique and technology. The purpose of this study is to review the current
      literature on technological advances in pediatric cataract surgery. METHODS:
      Review of literature on management of pediatric cataract surgery. RESULTS: The
      advent of vitrectomy machines and intraocular lenses (IOLs) has revolutionized
      pediatric cataract surgery. "Vitrectorhexis" has become a good alternative to
      manual capsulorhexis. Primary management of posterior capsule and limited
      anterior vitrectomy has reduced the incidence of visual axis opacification.
      Primary IOL implantation is becoming a standard of care in the youngest children.
      Single piece Acrysof(r) is preferred for in-the-bag implantation and 3-piece
      Acrysof(r) for sulcus implantation. Newer IOLs are being evaluated in pediatric
      eyes. Precise measurement of intraocular lens power and predicting refractive
      change are major challenges in long term care of children after surgery.
      CONCLUSION: New technology and surgical techniques have refined pediatric
      cataract surgery. It is critical to focus our efforts on precise biometry
      measurements, IOL power calculation, and designing IOLs that may address
      refractive changes in the growing pediatric eye.

PMID- 21091012
TI  - Endophthalmitis in the era of small gauge transconjunctival sutureless vitrectomy
      -meta analysis and review of literature.
AB  - PURPOSE: The goal of this study was to review, evaluate, and perform a meta
      analysis on the current literature that reports rates of postoperative
      endophthalmitis after small gauge transconjunctival sutureless vitrectomy (TSV)
      and compare it to 20-gauge pars plana vitrectomy (20G PPV). METHODS: We performed
      an extensive review of the current literature. We included only large comparative
      institutional reviews. Meta-analysis of these reviews was performed. RESULTS: We
      found six large retrospective comparative cases series on the 25-gauge (25G) TSV
      as compared to 20G PPV. The test for homogeneity for the meta-analysis indicates
      that the studies are not homogeneous and therefore the evidence is tentative.
      CONCLUSION: We cannot conclude that 25G TSV has a higher rate of postoperative
      endophthalmitis compared to the 20G PPV. Future retrospective or prospective
      trials need to take into consideration multiple factors.

PMID- 21091013
TI  - Drug delivery options for the treatment of ocular inflammation.
AB  - Treatments available for ocular inflammatory diseases and their associated
      complications have expanded significantly over the course of the last ten years.
      While corticosteroids are a mainstay of therapy for uveitis and macular edema,
      the methods of delivering corticosteroids have evolved. Intravitreal
      triamcinolone acetonide provides a local therapy for persistent cystoid macular
      edema (CME) and posterior uveitis. Other intravitreal therapies, such as
      bevacizumab and methotrexate, have also been used successfully in uveitic CME.
      Sustained release intravitreal implants, including the fluocinolone acetonide
      implant and the dexamethasone drug delivery system, offer an alternative therapy
      for chronic, recalcitrant posterior uveitis and CME. Their design was inspired by
      the ganciclovir implant, which prevented the progression of CMV retinitis in AIDS
      patients. Technological advances in drug delivery have supplied new treatments
      for patients with ocular inflammatory disease.

PMID- 21091015
TI  - Pharmacologic vitreolysis.
AB  - It is now well recognized that vitreous plays an important role in the
      pathogenesis of various retinal disorders. In many instances it can be addressed
      with pars plana vitrectomy, although this approach, like any surgery, has its
      limitations. The search for alternatives or adjunct to surgery has led to the
      development of pharmacologic vitreolysis. The use of intravitreal agents to alter
      the vitreous in order to reduce or eliminate its role in disease seems promising.
      The purpose of this article is to summarize the present knowledge on
      pharmacologic vitreolysis. A review of the different agents used and of ongoing
      trials will be presented. Also, current understanding of vitreous structure and
      its interaction with the retina will be discussed.

PMID- 21091016
TI  - Composite implants in oculoplastic surgery.
AB  - Composite devices containing two or more different material components or phases
      are seen with increasing frequency in oculoplastic, orbital, and lacrimal
      surgery. These combinations aim to improve mechanical and biological properties
      such as expansion, malleability, and strength in ways that have not been achieved
      with solitary material designs. Herein we review a variety of these new
      generation implants, including distensible orbital tissue expanders, hydrophilic
      osmotic expanders, titanium and polyethylene rigid fixation devices, non
      expandable hydrogels, laminated porcine intestine, and polyethylene-coated glass
      that likely herald a trend to more complex implantable devices in the future.

PMID- 21091014
TI  - Vitreous proteomics and diabetic retinopathy.
AB  - Diabetic retinopathy is the major cause of acquired blindness in working-age
      adults. Studies of the vitreous proteome have provided insights into the etiology
      of diabetic retinopathy and suggested potential molecular targets for treatments.
      Further characterization of the protein changes associated with the progression
      of this disease may suggest additional therapeutic approaches as well as reveal
      novel factors that may be useful in predicting risk and functional outcomes of
      interventional therapies. This article provides an overview of the various
      techniques used for proteomic analysis of the vitreous and details results from
      various studies evaluating vitreous of diabetic patients using the proteomic
      approach.

PMID- 21091017
TI  - A review of current technology used in evaluating visual function in glaucoma.
AB  - Glaucoma is a blinding disease associated with characteristic progressive optic
      nerve damage and visual field loss. Visual field testing in the form of automated
      perimetry is critical in the clinical diagnosis and monitoring of glaucoma.
      Functional tests can also be powerful research tools in clinical trials and in
      the field of neuroprotection. Standard automated perimetry (SAP) commonly used
      today, however, has its limitations. Early diagnosis of glaucoma based on
      functional measures can be challenging since it has been shown that retinal
      ganglion cell loss precedes defects detected on SAP. In addition, SAP is a
      subjective test prone to inter-test variability making the evaluation of disease
      progression problematic. Newer algorithms and functional tests are now being used
      and developed in an attempt to improve the accuracy in the detection of glaucoma
      and disease progression.

PMID- 21091018
TI  - Anterior segment optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a non-contact optical signal acquisition
      and processing device that provides magnified, high resolution cross-sectional
      images of ocular tissues. Development of anterior segment OCT (AS-OCT) offers the
      benefits of fine resolution and noninvasive examination to investigation of
      anterior segment anatomy to the depth of the iris plane. This imaging device has
      been utilized for investigation into a myriad of corneal and anterior segment
      disease. Recent technological advances toward three-dimensional visualization
      broaden the scope of AS-OCT in ophthalmologic evaluation. The AS-OCT is a
      valuable imaging tool whose use in research and clinical practice will continue
      to expand our knowledge and management of various ophthalmic conditions.

PMID- 21091020
TI  - Translation of the evidence into practice.

PMID- 21091021
TI  - A model of mosaic mentoring.

PMID- 21091022
TI  - Understanding and finding mentorship: a review for junior faculty.
AB  - BACKGROUND: Mentorship is considered central to physician success, and yet
      relatively few physicians report having formal mentors. Ever-increasing demands
      on physician time as well as multiple personal and professional responsibilities,
      make it challenging to find and sustain mentoring relationships. These challenges
      may be even greater in palliative medicine, a field with few mid-level to senior
      faculty and in which the supply of physicians is inadequate to meet the
      anticipated demand. DISCUSSION: In this article, we describe the attributes of
      the "ideal" mentor and the roles mentors commonly play in a protege's career. We
      then discuss a framework for optimizing one's chance of fostering mentoring
      relationships. We conclude by discussing the evolution of and transitions in
      mentoring relationships, as well as how one might transition from protege to
      mentor.

PMID- 21091023
TI  - Ketamine use in palliative care #132.

PMID- 21091024
TI  - African Americans and end-of-life care #204.

PMID- 21091025
TI  - "Is that all you got?".

PMID- 21091026
TI  - The real story: it's in the journal.

PMID- 21091028
TI  - Surviving chemotherapy for colon cancer and living with the consequences.
AB  - BACKGROUND: This article discusses peripheral neuropathy as a long-term side
      effect of oxaliplatin based chemotherapy, from a colon cancer survivor's
      perspective. Peripheral neuropathy is a common side effect of chemotherapy that
      affects quality of life for many cancer survivors. Severe and debilitating
      neuropathy negatively impacts both physical and emotional well-being. DISCUSSION:
      A better understanding of what cancer survivors with peripheral neuropathy
      experience is essential for health care professionals. More emphasis on symptom
      management and development of evidence based interventions will help improve
      quality of life for those who are affected by chemotherapy induced peripheral
      neuropathy.

PMID- 21091032
TI  - Talking about life-threatening illness. JPM Patient Information.

PMID- 21091034
TI  - Cell and virus genetics at the roots of gene therapy, retrovirology, and
      hematopoietic stem cell biology: Wolfram Ostertag (1937-2010).

PMID- 21091036
TI  - Percutaneous absorption of vapors in human skin.
AB  - CONTEXT: The absorption of vapors through the skin is an important issue because
      exposure of skin to chemicals in the ambient air occurs at all times. In regards
      to occupational health, accurately quantifying percutaneous absorption is crucial
      for worker health and safety. OBJECTIVE: Review the available data regarding the
      percutaneous absorption of vapors in humans. METHODS: We conducted a systematic
      search in Scopus((r)) and PubMed using keywords "vapor" and "percutaneous
      absorption" up until September 23, 2010. RESULTS: Eleven articles document the
      absorption of vapors in human skin in vivo. Seven articles utilized aromatic
      solvents including xylene and toluene, two tested 2-methoxyethanol, and two
      tested solely 2-butoxyethanol. Of the 11 articles, eight estimated the percentage
      of skin absorption compared with whole body exposure. Of the eight articles, four
      concluded that percutaneous absorption of aromatic solvent vapors from the air is
      likely to be insignificant and four concluded that dermal uptake of alcohol
      solvents caused significant absorption. CONCLUSION: Skin absorption of vapors is
      an important and relevant topic that has not been studied extensively. Further
      investigation of percutaneous vapor absorption is needed to ensure safe usage of
      solvent vapors in the workplace, and possibly elsewhere.

PMID- 21091037
TI  - Antibodies raised against different extracellular loops of the melanocortin-3
      receptor affect energy balance and autonomic function in rats.
AB  - Melanocortin receptors (MCR) play an important role in the regulation of energy
      balance and autonomic function. In the present studies, we used active
      immunization against peptide sequences from the first and the third extracellular
      loop (EL1 and EL3) of the MC3R to generate selective antibodies (Abs) against
      this MCR subtype in rats. Immunization with the EL1 peptide resulted in Abs that
      enhanced the effects of the endogenous ligand alpha-melanocyte-stimulating
      hormone (alpha-MSH), whereas immunization with the EL3 peptide resulted in Abs
      acting as non-competitive antagonists. The phenotype of immunized rats
      chronically instrumented with telemetry transducers was studied under four
      different conditions: a high-fat diet was followed by standard lab chow, by
      fasting, and finally by an intraperitoneal injection of lipopolysaccharide (LPS).
      Under high-fat diet, food intake and body weight were higher in the EL3 than in
      the EL1 or the control group. Blood pressure was increased in EL3 rats and
      locomotor activity was reduced. Plasma concentrations of triglycerides, insulin,
      and leptin tended to rise in the EL3 group. After switching to standard lab chow,
      the EL1 group showed a small significant increase in blood pressure that was more
      pronounced and associated with an increase in heart rate during food restriction.
      No differences between the EL1 or the EL3 group were observed after LPS
      injection. These results show that immunization against the MC3R resulted in the
      production of Abs with positive or negative allosteric properties. The presence
      of such Abs induced small changes in metabolic and cardiovascular parameters.

PMID- 21091040
TI  - The safety of clopidogrel.
AB  - IMPORTANCE OF THE FIELD: Clopidogrel is an antiplatelet prodrug widely used in
      acute coronary syndromes and after intravascular stent placement. Acute or
      chronic use can cause bleeding, a major adverse effect, which can lead to drug
      discontinuation or noncompliance with therapy. AREAS COVERED IN THIS REVIEW: The
      mechanism of action of clopidogrel, safety of different loading doses of
      clopidogrel, its use as a solitary antiplatelet agent and concomitant use with
      other antiplatelet agents such as aspirin and warfarin are discussed. Thrombotic
      thrombocytopenic purpura, a rare but important adverse event, has also been
      reviewed. Literature searches including randomized controlled trials were
      conducted in Medline. WHAT THE READER WILL GAIN: Clinicians will be able to
      understand the safety profile of using different doses of clopidogrel and the
      incidence of bleeding when used alone or in combination with other antiplatelet
      agents. TAKE HOME MESSAGE: Compared to aspirin, clopidogrel when taken alone
      causes less severe bleeding and less intracranial hemorrhage. Higher loading dose
      of clopidogrel is associated with increased bleeding. When combined with other
      antiplatelet agents, risk of bleeding increases, but like any other drug, the
      risks have to be weighed against potential benefits.

PMID- 21091041
TI  - Lapatinib for breast cancer: a review of the current literature.
AB  - IMPORTANCE OF THE FIELD: The identification of HER-2 expression as a predictive
      and prognostic marker revolutionized breast cancer. Trastuzumab, a humanized mAb,
      improves survival in both early and advanced HER-2 overexpressing breast cancer.
      However, many cancers either do not respond or develop resistance to this agent.
      Lapatinib is an oral tyrosine kinase inhibitor which has both HER-1 and -2
      activities and has been licensed for use in recurrent breast cancer that
      overexpresses HER-2. Studies of lapatinib in early breast cancer are ongoing.
      AREAS COVERED IN THIS REVIEW: A PubMed search was conducted using 'lapatinib' and
      'breast cancer' as the key words. All published works up to July 2010 were
      reviewed. A manual review of abstracts presented at the ASCO Annual meeting and
      the San Antonio Breast Cancer Symposium was conducted for the last 2 years. In
      this review, we summarize the current knowledge of lapatinib and pose questions
      which need to be addressed as we further expand our knowledge of the HER-2
      subtypes of breast cancer. WHAT THE READER WILL GAIN: The reader will gain an up
      to-date and comprehensive review of the current literature as it pertains to the
      safety and efficacy of lapatinib in the treatment of breast cancer. TAKE HOME
      MESSAGE: Lapatinib has provided an alternative for the treatment of advanced HER
      2 overexpressing breast cancer and is currently being assessed in early disease.

PMID- 21091042
TI  - PCM1-JAK2-fusion: a potential treatment target in myelodysplastic
      myeloproliferative and other hemato-lymphoid neoplasms.
AB  - IMPORTANCE OF THE FIELD: Activating mutations of the JAK2 gene are of tumorigenic
      significance in myeloproliferative neoplasms. Translocations involving the JAK2
      locus are of oncogenic importance in acute leukemias,
      myelodysplastic/myeloproliferative diseases and T-cell lymphomas. JAK2 locus
      gains, which are recurrent in Hodgkin's- and primary mediastinal B-cell lymphoma,
      are also efficient mechanisms of JAK2 activation. Recently, specific drugs
      blocking JAK2 have been developed and are currently in clinical trials. AREAS
      COVERED IN THIS REVIEW: We discuss possible mechanisms of deregulation and the
      significance of pericentriolar material 1 (PCM)1-JAK2 fusion/t(8;9)(p21-23;p23
      24) in hematolymphoid neoplasms. Such cases show morphological
      (myeloproliferaton, eosinophilia, myelofibrosis) and clinical (striking male
      predominance, aggressive course) similarities. Since increased JAK2
      oligomerization and tyrosine kinase domain activation is the probable oncogenic
      mechanism in this instance, such patients are promising candidates for JAK2
      inhibitor therapy. WHAT THE READER WILL GAIN: The reader will gain important
      insights considering PCM1-JAK2 fusion in hematologic malignancies. TAKE HOME
      MESSAGE: JAK2 is a tyrosine kinase with oncogenic potential in hematologic
      malignancies. It can be activated by point mutations, translocations and
      amplifications. Beyond malignancies associated with JAK2 point mutations, those
      associated with translocations might be suitable for tyrosine kinase inhibitors,
      which merits prospective evaluation.

PMID- 21091043
TI  - Retinoic acid receptor modulators: a perspective on recent advances and promises.
AB  - IMPORTANCE OF THE FIELD: Retinoids are currently used in the clinic for the
      treatment of skin diseases and acute promielocytic leukemia and are known to
      contribute to early development and organogenesis in embryo and throughout life.
      Most of these activities are primarily due to the binding of the retinoid to the
      retinoic acid receptors (RARs, subtypes alpha, beta and gamma). Ligand modulates,
      via allosteric conformational changes, the ability of RARs to interact with
      different sets of co-regulators. Structure-based insights on the ligand-binding
      domain of the ligand-bound RARs have clearly linked retinoid function to co
      activator (CoA) recruitment for agonists, CoA dissociation for antagonists and
      corepressor stabilization for inverse agonists. AREAS COVERED IN THIS REVIEW: To
      help understand ligand-modulated RAR action as a consequence of its interaction
      with different sets of co-regulators, we present the chemical engineering of
      subsets of retinoid chemotypes (rexinoids, i.e., the ligands of the retinoid X
      receptors, alpha, beta and gamma, with impact in the treatment of cancer and
      metabolic diseases, are not covered) that display the whole range of ligand
      functions, including subtype- and isotype-selectivities. WHAT THE READER WILL
      GAIN: An understanding of the correlation of retinoid ligand structure and
      function. Structural insights into ligand action and retinoid chemotypes.
      Potential for clinical application of retinoid receptor modulators. TAKE HOME
      MESSAGE: Potential pharmacological/therapeutic applications of these chemical
      tools extend beyond cancer prevention and therapy to the treatment of autoimmune
      and neurodegenerative diseases.

PMID- 21091044
TI  - Broken bodies, healing spirits: road trauma survivor's perceptions of pastoral
      care during inpatient orthopaedic rehabilitation.
AB  - PURPOSE: The aim of this article is to present findings from an Australian study
      that explored road trauma survivors' perceptions of spirituality and of a
      hospital-based pastoral care service throughout their inpatient rehabilitation.
      All participants had experienced severe orthopaedic injury. METHOD: A mixed
      method research design was used. The survey method elicited demographic, pastoral
      care contact and hospitalisation data. It included the Posttraumatic Growth
      Inventory (PTGI; Tedeschi and Calhoun 1996) and an adapted World Health
      Organisation Pastoral Intervention (WHO 2002) coding schema (Constitution of the
      World Health Organisation, basic documents, supplement. 45 ed.). An interview
      method was used to elicit information about participants' prior and current
      experiences of faith and spirituality, expectations, and experiences of the
      pastoral care service, and perceptions of the role of pastoral care in their
      rehabilitation. RESULTS: A thematic analysis of both quantitative and qualitative
      data identified nine core themes of supportive pastoral care. Pastoral care was
      seen as a valued and supportive intervention. Participants who completed the PTGI
      reported at least some degree of posttraumatic growth. CONCLUSIONS: Further
      research is recommended to examine the role and efficacy of pastoral care that is
      integral to road trauma recovery support.

PMID- 21091045
TI  - Incidence and risk factors of hip joint pain in children with severe cerebral
      palsy.
AB  - PURPOSE: Pain is a serious complication associated with hip dislocation in
      cerebral palsy (CP), limiting patient independence and quality of life. This
      study aimed to determine the frequency of pain in severe CP patients with hip
      dislocation and to reveal factors associated with the hip pain. METHODS: Seventy
      three consecutive new-intervention CP patients admitted to authors' institution
      with spastic quadriplegia, mean age 10.8 years (range 4.0-18.0 years) were
      enrolled: 31 females and 42 males, totally 99 dislocated hips. All patients were
      assessed level IV or V according to the Gross Motor Function Classification Scale
      (GMFCS) and had poor communication skills. Pain severity was evaluated according
      to the Numeric Rating Scale (NRS-11). Data concerning previously applied
      physiotherapy was collected to divide the patients into subgroups: A - no
      abduction therapy (n = 24), B - abduction therapy (n = 35) and C - abduction
      therapy and horse-back riding (n = 13). On the pelvic antero-posterior
      radiographs head migration percentage was measured to reveal hip dislocation.
      Femoral head cartilage degenerative lesions were evaluated for size and location
      in 45 hips undergoing surgical treatment. RESULTS: Overall pain prevalence was
      56%. The appearance of pain was associated with the patient age (p = 0.048),
      previous abduction physiotherapy (p < 0.00001), previous horse-back riding
      therapy (p < 0.00001) and anterior location of degenerative changes of the
      femoral head (p = 0.03). Pain intensity was related to the size of the
      degenerative cartilage lesions (p = 0.004) and to the degree of femoral
      anteversion (p < 0.0001). CONCLUSIONS: Extensive abduction exercises,
      hippotherapy and presence of degenerative cartilage lesions on the anterior part
      of femoral head may be considered risk factors for hip pain appearance in the
      dislocated hip of a child with severe spastic CP. Other associated factors are
      abduction exercise intensity, age, excessive femoral anteversion and size of
      degenerative cartilage lesions.

PMID- 21091046
TI  - Parental perceptions of participation of preschool children with and without
      mobility limitations: validity and reliability of the PART.
AB  - PURPOSE: This study provides information on the psychometric properties of a
      newly developed Dutch-language instrument for measuring parental perceptions of
      participation of preschool children (aged 2+ to 5+ years): the PART. METHOD: The
      PART was administered to parents of preschool children with (n = 51) and without
      (n = 285) physical developmental disabilities. In the group with disabilities,
      children with no or relatively minor mobility limitations (capability scores in
      mobility domain higher than one standard deviation below population mean) were
      excluded from all analyses. A subgroup of parents of children without
      disabilities (n = 56) filled out the PART a second time, after a five-week
      interval. Hypotheses regarding group differences in PART scores and correlations
      of PART scores with different, but related ICF-constructs were tested. Test
      retest reliability of the PART scales was examined. RESULTS: Expectations about
      group differences were confirmed. PART scores were associated in predicted ways
      with related constructs. PART scales showed good test-retest reliability (ICCs
      from 0.76 to 0.87). CONCLUSIONS: These findings indicate that the Dutch-language
      PART is a reliable and valid instrument for measuring parental perceptions of
      participation of preschool children with and without mobility limitations. The
      PART can prove useful for both clinical and research purposes.

PMID- 21091047
TI  - Measuring participation in individuals with Parkinson disease: relationships with
      disease severity, quality of life, and mobility.
AB  - PURPOSE: Our aims were to: (1) describe participation in people with Parkinson
      disease (PD), (2) evaluate the relationship between quality of life and
      participation and (3) determine the mobility measures which are predictive of
      participation. METHODS: Participants with idiopathic PD (n = 62) were tested off
      medication for participation (Activity Card Sort), quality of life (PDQ-39),
      disease severity (MDS-UPDRS) and mobility (Berg Balance Scale, Five Time Sit to
      Stand (FTSTS), Six Minute Walk, forward walking velocity, dual-task walking
      velocity and Freezing of Gait Questionnaire (FOGQ)). Relationships of all
      variables to participation were examined using Pearson correlations. Subsequent
      regression analysis was employed to determine the mobility measures which best
      predicted the participation. RESULTS: Participants with PD retained, on average,
      78.3% (SD = 15.6%) of total activities. Participation was negatively correlated
      with all PDQ-39 domains (r range -0.36 to -0.78, all p < 0.005) with the mobility
      domain having the strongest correlation. All mobility measures were significantly
      correlated with participation, with the final regression model including only
      FTSTS and FOGQ which combined explained 37% of the variance in participation.
      CONCLUSIONS: Participation is highly related to mobility-related QOL and may be
      most impacted by ability to stand up from a chair and freezing of gait in those
      with PD.

PMID- 21091048
TI  - Health of people with spinal cord injury in Singapore: implications for
      rehabilitation planning and implementation.
AB  - PURPOSE: This study aimed to provide a broad overview of the health of people
      with spinal cord injury (SCI) in Singapore, so as to highlight areas of potential
      need. These areas could then guide future research and rehabilitation programme
      development. METHODS: Demographic data, injury information and information about
      SCI-related secondary impairments, chronic conditions and their associated risk
      factors, medical and hospital utilisation, participation (Craig Handicap
      Assessment and Reporting Technique) and life satisfaction (Satisfaction with Life
      Scale) were collected via interviews from people living with traumatic SCI.
      RESULTS: On average, participants (50 men and 5 women) were aged 48.3 +/- 16.54
      years and had had their SCIs for 5 years. -75% with tetraplegia. The most
      prevalent SCI-related secondary impairments were pain, spasms, bladder problems,
      bowel problems and oedema. Chronic conditions and their associated risk factors
      were prevalent. Participation and life satisfaction scores were lower than those
      reported for similar populations cross-culturally. CONCLUSION: The study revealed
      several health areas that may be affecting the overall health of people with SCI
      in Singapore. By focusing on community reintegration and health promotion,
      physiotherapists and other rehabilitation professionals may augment health
      outcomes and improve the quality of life of this population in Singapore.

PMID- 21091049
TI  - Outcomes and adverse events from physiotherapy functional restoration for lumbar
      disc herniation with associated radiculopathy.
AB  - PURPOSE: To report the outcomes and adverse events of people diagnosed with
      lumbar disc herniation with associated radiculopathy (LDHR) who were treated with
      a physiotherapy functional restoration programme. METHOD: Data on functional
      outcome (Oswestry score), work status, global rating of change, and adverse
      events were extracted from the files of all people with LDHR treated by three
      physiotherapists using functional restoration principles from 2001 to 2009.
      RESULTS: Ninety-five participants were included. The Oswestry score reduced by a
      mean of 15.9 (95% CI, 11.8-20.1) points between baseline and discharge following
      a mean (SD) of 8.7 (9.4) months of treatment. The proportion of participants
      working full-time increased from 37% to 67% between baseline and discharge (p <
      0.001). Eighty per cent of participants reported overall improvement between
      baseline and discharge on the global rating of change scale (p < 0.001). Minor
      adverse events were reported by eight (8%) participants, while one (1%)
      participant developed adhesive capsulitis. CONCLUSION: People with LDHR who
      undertook a physiotherapy functional restoration programme achieved significant
      improvements in Oswestry disability scores, work status, and global rating of
      change, with few adverse events reported. A randomised controlled trial is
      warranted to determine the efficacy of functional restoration for people with
      this condition.

PMID- 21091050
TI  - Response of rat retinal capillary pericytes and endothelial cells to glucose.
AB  - AIM: The purpose of this study was to investigate the effects of hyperglycemia,
      its fluctuations, and glucose starvation on the expression of glucose-regulated
      protein 78/binding immunoglobulin protein (GRP78/BiP), one of the most commonly
      used markers of endoplasmic reticulum stress, in rat capillary pericytes and
      endothelial cells cultured separately and together. METHODS: Conditionally
      immortalized rat retinal pericyte and endothelial cell lines were cultured in
      dishes coated with collagen type I in Dulbecco's modified Eagle's medium
      containing 5.5  mM glucose. For cocultures, pericytes and endothelial cells were
      seeded together on rat tail collagen type I-coated cell culture plates. After 24 
      h of initial culture, the medium was replaced with serum-free medium containing 0
      100  mM glucose for periods of up to 72  h. GRP78/BiP, caspase-3, and nuclear
      factor-kappaB expression were investigated using western blots. RESULTS: No
      significant increase in GRP78/BiP expression was observed when pericytes,
      endothelial cells, or cocultures were exposed to either 25, 50, or 100  mM
      glucose for 48  h compared with the control level of 5.5  mM glucose. Similarly,
      no change in expression of GRP78/BiP was observed when media glucose levels were
      reduced from either 5.5 or 25 to 1  mM. GRP78/BiP expression significantly
      increased when cells were cultured for 24  h in glucose-deprived medium. This was
      accompanied by a time-dependent increase in the expression of caspase-3 and
      nuclear factor-kappaB. CONCLUSION: In diabetic retinopathy, hyperglycemia has
      been reported to induce apoptosis in retinal capillary vascular cells, but these
      studies suggest that the apoptosis is not linked to the expression of GRP78/BiP,
      one of the most commonly used markers of endoplasmic reticulum stress. However,
      GRP78/BiP-linked apoptosis may play a role in vascular changes associated with
      retinal ischemia/reperfusion.

PMID- 21091052
TI  - Prediction of siRNA potency using sparse logistic regression.
AB  - RNA interference (RNAi) can modulate gene expression at post-transcriptional as
      well as transcriptional levels. Short interfering RNA (siRNA) serves as a trigger
      for the RNAi gene inhibition mechanism, and therefore is a crucial intermediate
      step in RNAi. There have been extensive studies to identify the sequence
      characteristics of potent siRNAs. One such study built a linear model using LASSO
      (Least Absolute Shrinkage and Selection Operator) to measure the contribution of
      each siRNA sequence feature. This model is simple and interpretable, but it
      requires a large number of nonzero weights. We have introduced a novel technique,
      sparse logistic regression, to build a linear model using single-position
      specific nucleotide compositions which has the same prediction accuracy of the
      linear model based on LASSO. The weights in our new model share the same general
      trend as those in the previous model, but have only 25 nonzero weights out of a
      total 84 weights, a 54% reduction compared to the previous model. Contrary to the
      linear model based on LASSO, our model suggests that only a few positions are
      influential on the efficacy of the siRNA, which are the 5' and 3' ends and the
      seed region of siRNA sequences. We also employed sparse logistic regression to
      build a linear model using dual-position specific nucleotide compositions, a task
      LASSO is not able to accomplish well due to its high dimensional nature. Our
      results demonstrate the superiority of sparse logistic regression as a technique
      for both feature selection and regression over LASSO in the context of siRNA
      design.

PMID- 21091051
TI  - Gynecological history in chronic fatigue syndrome: a population-based case
      control study.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) affects disproportionately more women
      than men, and the condition is more common at perimenopause. We examined
      gynecological history events as risk factors for CFS. METHODS: In a case-control
      study from a randomly selected population sample from Wichita, Kansas, 36 women
      with CFS and 48 nonfatigued controls, of similar age, race, and body mass index
      (BMI), answered a structured gynecological history questionnaire. RESULTS: CFS
      cases and controls had the same mean age (51 years) and age at menarche (12
      years). Overall, a greater proportion of women with CFS than controls reported
      pelvic pain unrelated to menstruation (22.2% vs. 1.7%, p = 0.004), endometriosis
      (36.1% vs. 16.7, %, p = 0.046), and periods of amenorrhea (53.9 % vs. 46.2%, p =
      0.06). Compared to controls, women in the CFS group had a higher mean number of
      pregnancies (2.8 vs 2.0, p = 0.05) and gynecological surgeries (1.8 vs. 1.1, p =
      0.05). Similar proportions of the CFS (69.4%) and control (72.9%) groups were
      menopausal. Although menopausal women in the CFS and control groups had similar
      mean age (55.5 and 55.8, respectively), menopause occurred about 4.4 years
      earlier in the CFS group (41.7 years vs. 46.1 years, respectively, p = 0.11).
      Among menopausal women, 76% of the CFS group reported hysterectomy vs. 54.6% of
      controls (p = 0.09), and 56% of women with CFS reported oophorectomy vs. 34.3% of
      controls (p = 0.11). CONCLUSIONS: The higher prevalence of gynecological
      conditions and gynecological surgeries in women with CFS highlights the
      importance of evaluating gynecological health in these patients and the need for
      more research to clarify the chronologic and the pathophysiological relationships
      between these conditions and CFS.

PMID- 21091053
TI  - HarmonyDOCK: the structural analysis of poses in protein-ligand docking.
AB  - Molecular docking is a widely used method for lead optimization. However, docking
      tools often fail to predict how a ligand (the smaller molecule, such as a
      substrate or drug candidate) binds to a receptor (the accepting part of a
      protein). We present here the HarmonyDOCK, a novel method for assessing the
      docking software accuracy, and creating the scoring function which would
      determine consensus protein-ligand pose among those generated by available
      docking programs. Conformations for few hundred protein-ligand complexes with
      known three-dimensional structure were predicted on a benchmark set by set of
      different docking programs. On the basis of the derived ranking, the point of
      reference and the lower score limit were determined for subsequent
      investigations. The focus of the methodology is on the top-ranked poses, with the
      assumption being that the conformation of the docked molecules is the most
      accurate. We found out that some docking programs perform considerably better
      than the others, yet in all cases the proper selection of decoys, namely
      HarmonyDOCK, is needed for successful docking procedure.

PMID- 21091055
TI  - TNF inhibitors for uveitis: balancing efficacy and safety.

PMID- 21091054
TI  - Breastfeeding rates differ significantly by method used: a cause for concern for
      public health measurement.
AB  - OBJECTIVE: Accurate measurements of prevalence of "any" breastfeeding and
      "exclusive" breastfeeding help assess progress toward public health goals. We
      compared two commonly used data sources for measuring breastfeeding rates to
      assess agreement. METHODS: The National Immunization Survey (NIS) is used by the
      Centers for Disease Control and Prevention to measure progress toward national
      breastfeeding goals and obtains breastfeeding outcomes retrospectively at 19-35
      months. The California Newborn Screen (CNS) is a contemporaneous measure of
      breastfeeding during birth hospitalization and measures progress toward public
      health goals in California. We compared results for "any breastfeeding" and
      "exclusive breastfeeding" for California infants in the NIS to those in the CNS
      using descriptive statistics. RESULTS: Our results show that the two methods
      produce similar results for "any" breastfeeding at <4 days: 82.7%, 95% confidence
      interval (79.6%, 85.8%) in the NIS and 86.1% (86.0%, 86.2%) in the CNS. However,
      the two methods produce very different results for "exclusive" breastfeeding at
      <4 days: 60.4% (56.6%, 64.1%) in the NIS and 41.6% (41.5%, 41.7%) in the CNS.
      Rates of "exclusive" breastfeeding varied more for some subgroups; for Hispanics,
      estimates were 61.1% (56.1%, 66.1%) in the NIS and 29.7% (29.5%, 29.9%) in the
      CNS. CONCLUSIONS: There is good agreement between two disparate methods for
      assessing "any" breastfeeding rates. However, our findings suggest that the NIS,
      the CNS, or both are flawed measures of "exclusive" breastfeeding. Validated
      methods for measuring "exclusive" breastfeeding would allow improved monitoring
      of breastfeeding prevalence.

PMID- 21091056
TI  - Diagnosis of ocular sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis is a chronic inflammatory disorder with an unknown
      etiology characterized by noncaseating granulomas. The disorder is a
      multisystemic disease and affects many organs, including most often the lung,
      lymph nodes, skin, heart, liver, muscles, and the eye. MATERIAL AND METHODS:
      [corrected] Based on a review of the literature and on an algorithm generated in
      an international workshop on sarcoidosis, this article provides the reader with a
      schematic and simple approach to the diagnosis of ocular sarcoidosis.
      CONCLUSIONS: In a considerable proportion of cases it is the ophthalmologist who
      first sees patients presenting with the ocular expression of sarcoidosis. In
      countries where the incidence of sarcoidosis is common, like Japan, a complete
      workup should be performed, whereas in countries where the incidence of the
      disease is less high, a noninvasive approach may be warranted at first.

PMID- 21091057
TI  - Review for disease of the year: differential diagnosis of ocular sarcoidosis.
AB  - Sarcoid is characterized by the heterogeneity of its clinical expression as well
      as the silent nature and nonspecificity of many of its clinical findings.
      Diagnosis is often difficult due to its ability to mimic other diseases. In the
      absence of a highly specific confirmatory test, one must be cognizant of the
      features that distinguish these simulating conditions from sarcoidosis.
      Establishing an appropriate differential for patients suspected of having sarcoid
      requires one to consider the entire clinical presentation, the presence or
      absence of risk factors for masquerading disorders, patterns of resolution or
      progression, and response to treatment. This paper provides an overview of ocular
      conditions that may share part of the spectrum of clinical manifestations
      associated with sarcoid.

PMID- 21091058
TI  - Ocular immune privilege in the year 2010: ocular immune privilege and uveitis.
AB  - The phrase "immune privilege" was coined by Peter Medawar to describe the absence
      of an immune response to allografts placed into the anterior chamber of the eye
      or brain. We now understand that immune privilege is more than a passive
      microenvironment with a distinctive anatomical structure that holds back
      immunity. The ocular microenvironment actively engages the immune system with
      immunosuppressive biochemical mechanisms. The unique characteristics of ocular
      immune privilege appear designed to protect the eye from damage while preserving
      foveal vision, thus providing the host with a definite survival advantage.
      However, the protection is not always sufficient and the eye becomes susceptible
      to uveitis. Uveitis is an intraocular inflammatory disorder that encompasses a
      wide range of underlying etiologies. It may be idiopathic or associated with
      systemic disease or infection. Understanding the biochemistry of immune privilege
      has the potential to identify its weaknesses that allow for immunity to break
      through.

PMID- 21091060
TI  - Insulin resistance is independently associated with liver aminotransferases in
      diabetic patients without ultrasound signs of nonalcoholic fatty liver disease.
AB  - BACKGROUND: It has been shown that elevated levels of alanine and aspartate
      aminotransferases (ALT and AST) are associated with insulin resistance and type 2
      diabetes mellitus; however, the pattern of this association in diabetic patients
      with negative or mild steatosis is not well understood. The aim of this study was
      to assess the association between elevated liver enzymes and insulin resistance
      in diabetic subjects without ultrasound signs of nonalcoholic fatty liver disease
      (NAFLD) (i.e., with less than 30% steatosis). METHODS: In a cross-sectional
      study, a total of 670 diabetic subjects without established causes of liver
      injury were included. Patients with evidence of NAFLD in ultrasonography were not
      included. Fasting blood samples were obtained and plasma glucose, insulin,
      glycosylated hemoglobin (HbA1c), C-peptide, alkaline phosphatase, alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profile were
      measured. Three indices of insulin sensitivity/insensitivity: Homeostasis model
      assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity
      check index (QUICKI), and McAuley were also calculated. RESULTS: Elevated ALT was
      significantly (p < 0.001) correlated with fasting insulin, C-peptide, HOMA-IR,
      QUICKI, McAuley, and waist circumference. The same correlations were also
      observed for AST, which in all cases were weaker than ALT. Multivariate
      regression analysis showed that, among the above-mentioned variables, only HOMA
      IR and fasting insulin were independently correlated with both ALT and AST. This
      correlation was independent of body mass index (BMI) or waist circumference.
      CONCLUSION: In type 2 diabetes, in the absence of a detectable steatosis by
      ultrasonography, ALT and AST are associated with hyperinsulinemia and insulin
      resistance, independent of obesity. This finding possibly indicates that in
      diabetes a mild stage of steatosis is sufficient to mediate the association
      between insulin resistance and aminotransferases.

PMID- 21091061
TI  - "Daily" dialysis--lessons from a randomized, controlled trial.

PMID- 21091063
TI  - Hip circumference and incident metabolic risk factors in Chinese men and women:
      the People's Republic of China study.
AB  - BACKGROUND: The associations between adiposity and metabolic risk factors have
      been suggested to vary across ethnicities. Studies in Caucasians have shown that
      after adjusting for waist circumference and body mass index (BMI), a larger hip
      circumference may be protective for metabolic risk factors. To our knowledge,
      these associations have never been examined in a Chinese population. METHODS:
      Baseline (1987-1988) and follow-up (1993-1994) data were from the People's
      Republic of China Study (n = 1,144 men, n = 1,776 women). Logistic models were
      stratified by sex and adjusted for age, smoking, center, and education. Incidence
      differences (ID) comparing the sex specific 85(th) percentile to the 15(th)
      percentile of hip circumference were computed for elevated blood pressure, blood
      glucose and triglycerides, low high-density lipoprotein cholesterol (HDL-C), and
      multiple metabolic abnormalities (three or more of the aforementioned). RESULTS:
      In models adjusted for waist circumference and BMI, the ID [95% confidence
      interval (CI)] per 1,000 persons associated with a 12-cm larger hip were -132 (
      237, -26) for low HDL-C; -85 (-138, -31) for elevated triglycerides; and -49 (
      83, -4) for multiple metabolic abnormalities. In males, a larger hip
      circumference was not associated with a reduction of incident risk factors,
      although the ID tended to be negative. CONCLUSIONS: In Chinese women, greater
      mass in the lower trunk region was inversely associated with incident high
      triglycerides, low HDL-C, and multiple metabolic abnormalities when adjusted for
      general and central adiposity. This association was not detected in men.
      Additional research is needed to better understand the mechanisms by which fat at
      different depots results in differential risk.

PMID- 21091064
TI  - Exploring the landscape of protein-ligand interaction energy using probabilistic
      approach.
AB  - Analysis of protein/small molecule interactions is crucial in the discovery of
      new drug candidates and lead structure optimization. Small biomolecules (ligands)
      are highly flexible and may adopt numerous conformations upon binding to the
      protein. Using computer simulations instead of sophisticated laboratory
      procedures may significantly reduce cost of some stages of drug development.
      Inspired by probabilistic path planning in robotics, stochastic roadmap
      methodology can be regarded as a very interesting approach to effective sampling
      of ligand conformational space around a protein molecule. Protein-ligand
      interactions are divided into two parts: electrostatics, modeled by the Poisson
      Boltzmann equation, and van der Waals interactions, represented by the Lennard
      Jones potential. The results are promising; it can be shown that locations of
      binding sites predicted by the simulation are in agreement with those revealed by
      experimental x-ray crystallography of protein-ligand complexes. We wanted to
      extend our knowledge beyond the current molecular modeling tools to arrive at a
      better understanding of the ligand-binding process. To this end, we investigated
      a two-level model of protein-ligand interaction and sampling of ligand
      conformational space covering the entire surface of protein target.

PMID- 21091065
TI  - Chinese map of minimally invasive therapy and technology.

PMID- 21091066
TI  - Safety, feasibility, and mid-term follow-up of Willis stent graft placement in
      the treatment of symptomatic complicated intra- or extra-cranial aneurysms: a
      multicenter experience.
AB  - We report the technical success rate and mid-term follow-up results after
      deploying stent-grafts to treat a cohort of patients with symptomatic complicated
      intra- or extracranial aneurysms (SCIEAs). This study was a retrospective review
      of 58 patients (39 male; mean age 40.4 +/- 12.3 years) with 60 SCIEAs treated by
      67 Willis covered stents at three medical centers in China between April 2005 and
      January 2010. The locations of the SCIEAs were as follows: Intracranial internal
      carotid artery (ICA) in 54 patients, extracranial ICA in one, intracranial
      vertebral artery (VA) in three and extra-cranial VA in two. Surgery was
      successful in 59 (98.3%) SCIEAs. Total exclusion was immediately achieved in 48
      SCIEAs, and minor endoleaks were present in 11. Acute thrombosis occurred in two
      patients and hemorrhage in one. Follow-up angiography (mean 13.8 +/- 8.9 months)
      revealed that 49 of 52 (94.2%) aneurysms were completely isolated, with mild in
      stent stenosis in only two patients and in-stent occlusion in one patient. Willis
      stent-graft application is an alternative therapy to treat SCIEAs in either intra
      or extracranial ICAs or VAs. In the case of a tortuous intracranial ICA or
      potential side branch coverage, however, it is still not a first choice.

PMID- 21091062
TI  - In-center hemodialysis six times per week versus three times per week.
AB  - BACKGROUND: In this randomized clinical trial, we aimed to determine whether
      increasing the frequency of in-center hemodialysis would result in beneficial
      changes in left ventricular mass, self-reported physical health, and other
      intermediate outcomes among patients undergoing maintenance hemodialysis.
      METHODS: Patients were randomly assigned to undergo hemodialysis six times per
      week (frequent hemodialysis, 125 patients) or three times per week (conventional
      hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes
      were death or change (from baseline to 12 months) in left ventricular mass, as
      assessed by cardiac magnetic resonance imaging, and death or change in the
      physical-health composite score of the RAND 36-item health survey. Secondary
      outcomes included cognitive performance; self-reported depression; laboratory
      markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates
      of hospitalization and of interventions related to vascular access. RESULTS:
      Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the
      weekly standard Kt/V(urea) (the product of the urea clearance and the duration of
      the dialysis session normalized to the volume of distribution of urea) was
      significantly higher in the frequent-hemodialysis group than in the conventional
      hemodialysis group (3.54+/-0.56 vs. 2.49+/-0.27). Frequent hemodialysis was
      associated with significant benefits with respect to both coprimary composite
      outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95%
      confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in
      the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients
      randomly assigned to frequent hemodialysis were more likely to undergo
      interventions related to vascular access than were patients assigned to
      conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent
      hemodialysis was associated with improved control of hypertension and
      hyperphosphatemia. There were no significant effects of frequent hemodialysis on
      cognitive performance, self-reported depression, serum albumin concentration, or
      use of erythropoiesis-stimulating agents. CONCLUSIONS: Frequent hemodialysis, as
      compared with conventional hemodialysis, was associated with favorable results
      with respect to the composite outcomes of death or change in left ventricular
      mass and death or change in a physical-health composite score but prompted more
      frequent interventions related to vascular access. (Funded by the National
      Institute of Diabetes and Digestive and Kidney Diseases and others;
      ClinicalTrials.gov number, NCT00264758.).

PMID- 21091067
TI  - Long-term outcome of laparoscopic total mesorectal excision for middle and low
      rectal cancer.
AB  - This study aimed to assess the feasibility and long-term outcome of laparoscopic
      total mesorectal excision for middle and lower rectal cancer. Retrospective
      assessment was performed on 612 patients with middle and low rectal cancer in the
      surgery department of our hospital. Three-hundred and three patients underwent
      laparoscopic total mesorectal excision (LTME), and 309 patients underwent open
      TME (OTME). All the data regarding patient details, operative variables and the
      short- and long-term outcomes were collected and compared. The sphincter
      preserving rates of the two groups were similar. The conversion rate in LTME was
      2.31% (seven cases). Fourteen cases (6.67%) of protective diverting stoma were
      fashioned in the LTME group compared with 57 cases (26.64%) in the OTME group.
      The postoperative morbidity was the same in these two groups, while the
      postoperative period until bowel movement and hospital discharge was shorter in
      the LTME group (P < 0.01). The median follow-up period was 34 (6-81) months for
      the LTME group and 36 (6-81) months for the OTME group. Local recurrence rates,
      the five-year disease-free survival rate and the five-year overall survival rate
      showed no difference between the two groups. Laparoscopic surgery is feasible and
      safe in patients with middle and lower rectal cancer and can provide favorable
      short-term and long-term outcomes.

PMID- 21091068
TI  - Selective laparoscopic lateral dissection of regional micrometastasis in rectal
      carcinoma--ten years single center experience.
AB  - Although total mesorectal excision (TME) has been generally accepted as a
      principle of rectal cancer surgery, the corresponding laparoscopic approach still
      needs evaluation in depth, especially the controversial dissection of lateral
      pelvic areas. At our center, 982 patients with rectal cancers received
      laparoscopic or laparoscopic-assisted surgery during the past ten years. Short
      term results showed an anastomic leakage rate of 4.2% (29/683) in patients with
      anal sphincter preservation and an average hospitalization of 8.8 days. Sixty-two
      cases (6.3%) suffered postoperative urinary dysfunction while well-controlled
      defecation was observed in 87.6% cases that underwent colo-rectal/colo-anal
      anastomosis. According to our experience, the laparoscope amplifies the local
      view within the narrow pelvis, thus facilitating the identification of surgical
      plane and adjacent structures. The radial, proximal and distal distribution of
      mesorectal micrometastases underline the importance of total mesorectal excision
      and the sharp dissection between parietal and visceral pelvic fascia is essential
      for better clearance and nerve protection. Lateral metastasis was more common in
      lower located cancers while laparoscopic lateral dissection is practical and safe
      when performed by trained surgeons. Lateral dissection is advised when
      preoperative imaging or intraoperative exploration suggest the existence of
      lateral metastasis.

PMID- 21091069
TI  - A modified method of using laparoscopic compression anastomosis clip for
      gastrointestinal anastomosis.
AB  - The aim of this study was to validate a modified method of using a laparoscopic
      compression anastomosis clip (LapCAC) for gastrointestinal anastomosis in an
      animal experiment and two clinical cases. Anastomotic surgery of the upper
      digestive tract was performed on dogs using the conventional and modified methods
      for LapCAC. The animals were sacrificed postoperatively at different time points
      to obtain sections from the anastomotic site for pathologic study. Anastomotic
      outcomes of the two methods were also verified in two clinical cases. The animal
      experiments and the two clinical cases showed that no anastomotic leakage
      occurred with the modified method, and that the new method was simple, convenient
      and reliable as compared with the conventional method. The mean time of placing
      the anastomosis clip was shorter, and the mean numbers of operation attempts,
      secondary actions and sutures in the operating holes were reduced. The serosa at
      the anastomosis healed completely, the muscular layer and submucosal fibers
      proliferated well, and the anastomosis was covered with mucosa within two weeks
      after the operation. LapCAC offered a better surgical outcome when it was used
      according to the modified method, where anastomoses formed smoothly and
      completely within two weeks after the operation.

PMID- 21091070
TI  - A new order of D2 lymphadenectomy in laparoscopic gastrectomy for cancer: live
      anatomy-based dissection.
AB  - It was the aim of this study to develop a methodology for dissection in
      laparoscopic distal gastrectomy with D2 lymphadenectomy (D2 LDG) for gastric
      cancer. One-hundred and thirty-two patients with distal gastric cancer underwent
      D2 LDG with a novel sequence of lymph node dissection between August 2004 and
      June 2008. Live anatomy in each step was observed simultaneously to ensure and
      confirm the newly developed methodology. Dissections in LDG were standardized as
      sequential steps: Dividing the gastrocolic ligament and getting access to the
      prepancreatic space--lymph node dissection in the lower left area--lymph node
      dissection in the lower right area--lymph node dissection in the upper right area
      -lymph nodes dissection centrally--lymph node dissection between liver and
      stomach. All dissections were successfully performed in peripancreatic spaces and
      their extensions. Gastric vessels were located by special landmarks, traced along
      vascular trunks and bifurcations, and identified by fine dissection technique in
      vaginavasorum. Sequential dissection around the pancreas was an effective method
      for D2 LDG. It was ensured by anatomical knowledge in each step: Vessels and
      fascial spaces around a central landmark, the pancreas.

PMID- 21091073
TI  - Reduced cardioprotective action of adiponectin in high-fat diet-induced type II
      diabetic mice and its underlying mechanisms.
AB  - Diabetes exacerbates ischemic heart disease morbidity and mortality via
      incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial
      ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's
      cardioprotective actions are altered in diabetes, a pathologic condition with
      endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced
      diabetic mice and normal diet (ND) controls were subjected to MI via coronary
      artery ligation, and given vehicle or APN globular domain (gAPN, 2 MUg/g) 10 min
      before reperfusion. Compared to ND mice (where gAPN exerted pronounced
      cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN
      dose was requisite to achieve cardioprotective extent seen in ND mice (i.e.,
      infarct size, apoptosis, and cardiac function). APN reduces MI/R injury via AMP
      activated protein kinase (AMPK)-dependent metabolic regulation and AMPK
      independent antioxidative/antinitrative pathways. Compared to ND, HD mice
      manifested significantly blunted gAPN-induced AMPK activation, basally and after
      MI/R (p<0.05). Although both low- and high-dose gAPN equally attenuated MI/R
      induced oxidative stress (i.e., NADPH oxidase expression and superoxide
      production) and nitrative stress (i.e., inducible nitric oxide synthase
      expression, nitric oxide production, and peroxynitrite formation) in ND mice,
      only high-dose gAPN efficaciously did so in HD mice. We demonstrate for the first
      time that HD-induced diabetes diminished both AMPK-dependent and AMPK-independent
      APN cardioprotection, suggesting an unreported diabetic heart APN resistance.

PMID- 21091076
TI  - A central role of heme oxygenase-1 in cardiovascular protection.
AB  - The intrinsic defense mechanisms of the body are critical in protecting tissues
      from injury in response to pathological stress. Heme oxygenase-1 (HO-1), a stress
      response protein, is induced in response to various pathological stimuli to serve
      a cytoprotective function. By degrading the oxidant heme and generating the
      antioxidant bilirubin and anti-inflammatory molecule carbon monoxide, HO-1 may
      protect cell from injury due to oxidative and pathological stress. Oxidative
      stress in the heart caused by ischemia and reperfusion leads to cardiomyocyte
      death and subsequent myocardial infarction. Vascular diseases including
      atherosclerosis, graft failure, and restenosis are all associated with reactive
      oxygen species-induced injury and inflammation. Given that cardiovascular disease
      is the leading cause of death worldwide, there is considerable interest in
      developing new strategies for preventing and treating cardiovascular disease.
      Since HO-1 is induced in the heart and blood vessels in response to various
      stresses, a role of HO-1 has been implicated in cardiovascular homeostasis.
      Numerous studies using pharmacological method or genetic approach have since
      demonstrated the cardiovascular protective function of HO-1. Importantly, a
      number of studies have associated human HO-1 gene promoter polymorphisms with
      risk for vascular diseases. Taken together, HO-1 has a great therapeutic
      potential for cardiovascular disease.

PMID- 21091075
TI  - Ryanodine receptor: a new therapeutic target to control diabetic cardiomyopathy.
AB  - Diabetes mellitus is a major risk factor for cardiovascular complications.
      Intracellular Ca(2+) release plays an important role in the regulation of muscle
      contraction. Sarcoplasmic reticulum Ca(2+) release is controlled by dedicated
      molecular machinery, composed of a complex of cardiac ryanodine receptors
      (RyR2s). Acquired and genetic defects in this complex result in a spectrum of
      abnormal Ca(2+) release phenotypes in heart. Cardiovascular dysfunction is a
      leading cause for mortality of diabetic individuals due, in part, to a specific
      cardiomyopathy, and to altered vascular reactivity. Cardiovascular complications
      result from multiple parameters, including glucotoxicity, lipotoxicity, fibrosis,
      and mitochondrial uncoupling. In diabetic subjects, oxidative stress arises from
      an imbalance between production of reactive oxygen and nitrogen species and
      capability of the system to readily detoxify reactive intermediates. To date, the
      etiology underlying diabetes-induced reductions in myocyte and cardiac
      contractility remains incompletely understood. However, numerous studies,
      including work from our laboratory, suggest that these defects stem in part from
      perturbation in intracellular Ca(2+) cycling. Since the RyR2s are one of the well
      characterized redox-sensitive ion channels in heart, this article summarizes
      recent findings on redox regulation of cardiac Ca(2+) transport systems and
      discusses contributions of redox regulation to pathological cardiac function in
      diabetes.

PMID- 21091077
TI  - Endothelial progenitor cells and exercise-induced redox regulation.
AB  - Endothelial progenitor cells (EPCs) are thought to participate in endothelial
      cell regeneration and neovascularization in either a direct or an indirect way.
      The number of circulating EPCs is influenced by many factors like disease status,
      medication, age, and fitness level and is an independent predictor of disease
      progression and cardiovascular events. Experimental as well as clinical studies
      during the last 10 years clearly demonstrated that physical exercise training has
      a beneficial effect on endothelial function, which is a clear predictive value
      for cardiovascular mortality. Over the last years mainly clinical studies
      provided solid evidence for an exercise training induced mobilization of EPCs
      from the bone marrow, thereby possibly influencing the regeneration of the
      endothelial cell layer. This review will discuss the mechanisms how exercise
      induces mobilization of EPCs from the bone marrow with a focus on the influence
      on the redox balance.

PMID- 21091074
TI  - Toll-like receptors: new players in myocardial ischemia/reperfusion injury.
AB  - Innate immune and inflammatory responses have been implicated in myocardial
      ischemia/reperfusion (I/R) injury. However, the mechanisms by which innate
      immunity and inflammatory response are involved in myocardial I/R have not been
      elucidated completely. Recent studies highlight the role of Toll-like receptors
      (TLRs) in the induction of innate immune and inflammatory responses. Growing
      evidence has demonstrated that TLRs play a critical role in myocardial I/R
      injury. Specifically, deficiency of TLR4 protects the myocardium from ischemic
      injury, whereas modulation of TLR2 induces cardioprotection against ischemic
      insult. Importantly, cardioprotection induced by modulation of TLRs involves
      activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway,
      suggesting that there is a crosstalk between TLRs and PI3K/Akt signaling
      pathways. In addition, TLRs also associate with other coreceptors, such as
      macrophage scavenger receptors in the recognition of their ligands. TLRs are also
      involved in the induction of angiogenesis, modulation of stem cell function, and
      expression of microRNA, which are currently important topic areas in myocardial
      I/R. Understanding how TLRs contribute to myocardial I/R injury could provide
      basic scientific knowledge for the development of new therapeutic approaches for
      the treatment and management of patients with heart attack.

PMID- 21091078
TI  - Radiation as a risk factor for cardiovascular disease.
AB  - Abstract population are ubiquitous background radiation and medical exposure of
      patients. From the early 1980s to 2006, the average dose per individual in the
      United States for all sources of radiation increased by a factor of 1.7-6.2 mSv,
      with this increase due to the growth of medical imaging procedures. Radiation can
      place individuals at an increased risk of developing cardiovascular disease.
      Excess risk of cardiovascular disease occurs a long time after exposure to lower
      doses of radiation as demonstrated in Japanese atomic bomb survivors. This review
      examines sources of radiation (atomic bombs, radiation accidents, radiological
      terrorism, cancer treatment, space exploration, radiosurgery for cardiac
      arrhythmia, and computed tomography) and the risk for developing cardiovascular
      disease. The evidence presented suggests an association between cardiovascular
      disease and exposure to low-to-moderate levels of radiation, as well as the well
      known association at high doses. Studies are needed to define the extent that
      diagnostic and therapeutic radiation results in increased risk factors for
      cardiovascular disease, to understand the mechanisms involved, and to develop
      strategies to mitigate or treat radiation-induced cardiovascular disease.

PMID- 21091080
TI  - Tape transfer sectioning of tissue microarrays introduces nonspecific
      immunohistochemical staining artifacts.
AB  - Tissue microarrays place tens to hundreds of formalin fixed, paraffin embedded
      tissue cores into a paraffin block in a systematic grid pattern that permits
      their simultaneous evaluation in a single section. The fragmented nature of the
      tissue cores often makes sectioning of tissue microarrays difficult so that the
      resulting disks of tissue lose their shape, fracture or fall out of the paraffin
      section altogether. We have evaluated an alternative sectioning protocol for
      stabilizing the tissue microarray surface by placing an adhesive tape "window"
      over the face of the paraffin block prior to sectioning. Once sectioned, the
      tape/sections are transferred directly onto coated microscope slides, thereby
      avoiding routine floating of sections on a water bath. After sectioning with
      either the tape transfer or standard protocols, slides were stained either using
      hematoxylin and eosin or immunohistochemistry using antibodies to S-100 protein
      and the tissue specific antigens, keratin (AE1/3) and the leukocyte common
      antigen CD45. We found that the tape method produced thicker sections that were
      darker and more densely packed with loss of tissue definition compared to
      sections prepared using water bath flotation. Quantitative image analysis of
      immunohistochemical staining demonstrated that the tape method produced a higher
      incidence of nonspecific staining, which raised the potential for false positive
      staining.

PMID- 21091079
TI  - Systemic adiponectin malfunction as a risk factor for cardiovascular disease.
AB  - Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic
      processes. The 30 kDa protein originates from adipose tissue, with full-length
      and globular domain circulatory forms. A collagenous domain within Ad leads to
      spontaneous self-assemblage into various oligomeric isoforms, including trimers,
      hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors
      for Ad have been identified, with differing concentration distribution in various
      body tissues. The major intracellular pathway activated by Ad includes
      phosphorylation of AMP-activated protein kinase, which is responsible for many of
      Ad's metabolic regulatory, anti-inflammatory, vascular protective, and anti
      ischemic properties. Additionally, several AMP-activated protein kinase
      independent mechanisms responsible for Ad's anti-inflammatory and anti-ischemic
      (resulting in cardioprotective) effects have also been discovered. Since its 1995
      discovery, Ad has garnered considerable attention for its role in diabetic and
      cardiovascular pathology. Clinical observations have demonstrated the association
      of hypoadiponectinemia in patients with obesity, cardiovascular disease, and
      insulin resistance. In this review, we elaborate currently known information
      about Ad malfunction and deficiency pertaining to cardiovascular disease risk
      (including atherosclerosis, endothelial dysfunction, and cardiac injury), as well
      as review evidence supporting Ad resistance as a novel risk factor for
      cardiovascular injury, providing insight about the future of Ad research and the
      protein's potential therapeutic benefits.

PMID- 21091081
TI  - Multicolor counterstaining for immunohistochemistry -- a modified Movat's
      pentachrome.
AB  - The application of "histochemical" staining procedures has been substantially
      replaced by immunostaining of specific molecular tissue components. The limited
      range of colors resulting from routine immunohistochemistry, however, can limit
      assessment of the general microscopic tissue organization. Consequently we have
      adapted a polychromatic histochemical counterstaining procedure based on Movat's
      pentachrome staining sequence for use with immunohistochemical procedures. The
      value of Movat's original method when applied as an immunohistochemical
      counterstain is limited by its use of iron hematoxylin and by fact that the
      resulting color combination is difficult to distinguish from the colors of
      routine immunohistochemical staining. Our variant pentachrome stains the same
      tissue components as Movat's stain; however, owing to a modification of the acid
      fuchsin staining step, it provides a strong color contrast with the reaction
      product resulting from immunostaining using diaminobenzidine as the chromogen.
      Multicolor counterstaining for immunohistochemistry offers a new approach to
      tissue analysis, especially when stromal-epithelial relations of normal and
      neoplastic tissues are considered.

PMID- 21091082
TI  - The development of an Afrikaans test for sentence recognition thresholds in
      noise.
AB  - OBJECTIVE: The development of a valid and reliable Afrikaans test of sentence
      recognition thresholds in noise. DESIGN: A collection of sentences was developed,
      rated for naturalness and grammatical complexity, and digitally recorded using a
      female speaker. Sentences found to have similar psychometric curve slopes, with
      equivalent intelligibility at three different noise levels, were arranged into 22
      phonemically matched lists of ten sentences each. List equivalence was evaluated
      in normal-hearing listeners in full and reduced bandwidth conditions. Test-retest
      reliability of the remaining lists was evaluated in a second group of listeners.
      STUDY SAMPLE: All listeners were native speakers of Afrikaans with normal
      hearing. For evaluation of list equivalence, ten listeners were used. Twenty
      other listeners were used to evaluate test-retest reliability. RESULTS: A
      collection of eighteen phonemically matched lists was produced. Lists were found
      to be of equivalent difficulty in full and reduced bandwidth conditions, and to
      have good test-retest reliability in normal-hearing listeners. The average
      recognition threshold of these lists was -2.73 dB signal-to-noise ratio (standard
      deviation = 0.64 dB), and within-subject variability was 1.22 dB. CONCLUSIONS:
      The developed test provides a valid and reliable means of measuring sentence
      recognition thresholds in noise in Afrikaans.

PMID- 21091083
TI  - Experiences of the use of FOX, an intelligent agent, for programming cochlear
      implant sound processors in new users.
AB  - OBJECTIVE: This report describes the application of the software tool "Fitting to
      Outcomes eXpert" (FOX) in programming the cochlear implant (CI) processor in new
      users. FOX is an intelligent agent to assist in the programming of CI processors.
      The concept of FOX is to modify maps on the basis of specific outcome measures,
      achieved using heuristic logic and based on a set of deterministic "rules".
      DESIGN: A prospective study was conducted on eight consecutive CI-users with a
      follow-up of three months. STUDY SAMPLE: Eight adult subjects with postlingual
      deafness were implanted with the Advanced Bionics HiRes90k device. The implants
      were programmed using FOX, running a set of rules known as Eargroup's EG0910
      advice, which features a set of "automaps". The protocol employed for the initial
      3 months is presented, with description of the map modifications generated by FOX
      and the corresponding psychoacoustic test results. RESULTS: The 3 month median
      results show 25 dBHL as PTA, 77% (55 dBSPL) and 71% (70 dBSPL) phoneme score at
      speech audiometry and loudness scaling in or near to the normal zone at different
      frequencies. CONCLUSIONS: It is concluded that this approach is feasible to start
      up CI fitting and yields good outcome.

PMID- 21091084
TI  - Acute adult T-cell leukemia/lymphoma (ATL) presenting with cutaneous purpuric
      lesions: a rare presentation.

PMID- 21091085
TI  - Impact of symptom burden on health related quality of life of cancer survivors in
      a Danish cancer rehabilitation program: A longitudinal study.
AB  - INTRODUCTION: Little research has been conducted on the effect of self-reported
      rating of symptom severity on quality of life (QoL) among cancer survivors. The
      aim of the study was to examine the prevalence of symptoms and whether
      information about self-reported symptom severity adds value to QoL measurements.
      MATERIAL AND METHODS: A questionnaire including the EORTC QLQ-C30 and an
      empirically derived symptom check-list was completed by 2 486 cancer survivors
      participating in a rehabilitation program at baseline and at 1, 6 and 12 months'
      follow-up. We used multivariate linear regression models to evaluate the
      association between QoL and the dichotomous variables for perceived symptom
      severity (high vs. low) and cancer stage (high vs. low), with adjustment for age,
      gender, education and time since diagnosis. RESULTS: Of the 2 379 participants
      who reported having one or more symptoms, 1 479 (62%) considered the reported
      symptom to be severe. This subgroup had significantly poorer QoL at baseline for
      all sites, ranging from -15.9 to -10.2, compared to those who did not regard
      their symptom as severe. Significantly lower baseline levels on all functional
      subscales were seen for all sites in association with high perceived symptom
      severity (range from -9.9 to -3.0 (physical functioning), from -21.1 to -13.0
      (social functioning), from -18.8 to -8.5 (emotional functioning), and from -18.4
      to -9.6 (cognitive functioning). The impairment of physical, social, emotional,
      and cognitive functioning persisted through 12 months for participants with
      cancer of the breast, lung and those with lymphomas, although not all reached
      significance. DISCUSSION: Cancer survivors, irrespective of cancer site,
      experience a high burden of symptoms. Thorough monitoring and assessment of
      symptoms and careful scrutiny of cancer survivors' perceptions of how symptoms
      affect their lives is critical for clinical identification of patients who might
      benefit from enhanced medical attention and may be an important supplement to QoL
      measures.

PMID- 21091086
TI  - Socioeconomic position and breast reconstruction in Danish women.
AB  - Few studies have been conducted on the socioeconomic position of women undergoing
      breast reconstruction, and none have been conducted in the Danish population. We
      investigated the association between educational level and breast reconstruction
      in a nationwide cohort of Danish women with breast cancer. MATERIAL AND METHODS:
      From nationwide registers, 13 379 women aged 30-80 years who had been treated by
      mastectomy for breast cancer in Denmark in 1999-2006 were identified and followed
      up through November 2009. Multivariate logistic regression models were used to
      investigate the simultaneous influence of educational level on the likelihood of
      having immediate or delayed (up to three years after mastectomy) breast
      reconstruction, with adjustment for age, breast cancer characteristics,
      comorbidity, socioeconomic variables and availability of plastic surgery services
      at each woman's affiliated hospital. RESULTS: The odds ratios (ORs) for both
      immediate and delayed breast reconstruction increased significantly with level of
      education. Being affiliated to a hospital with a plastic surgery department
      increased the likelihood of both immediate (adjusted OR, 4.02; 95% confidence
      interval [CI], 2.81-5.75) and delayed breast reconstruction (adjusted OR, 1.41;
      95% CI, 1.26-1.66). There was no association between education and breast
      reconstruction among 30-44 year old women, regardless of type of breast
      reconstruction; however, medium or higher education was significantly associated
      with a fourfold increase in the OR for immediate breast reconstruction in women
      aged 45-59 years and a more than twofold increase in the OR for delayed breast
      reconstruction in women aged 60-80 years compared to women with short education.
      CONCLUSION: Increasing education was associated with increasing odds for having
      immediate or delayed breast reconstruction, but only in the older age groups. The
      offer of breast reconstruction appears to be unequally distributed in Denmark,
      and living in an area where the hospital has a plastic surgery department
      significantly increased the odds for having breast reconstruction.

PMID- 21091087
TI  - How can young women be encouraged to attend cervical cancer screening?
      Suggestions from face-to-face and internet focus group discussions with 30-year
      old women in Stockholm, Sweden.
AB  - BACKGROUND: cervical cancer screening (CCS) using Pap-smears has been carried out
      for decades and is still an essential tool for secondary cancer prevention. Focus
      has traditionally been on what hinders women's attendance, instead of researching
      this issue from a positive standpoint, i.e. what factors encourage women to take
      a Pap-smear? In this article, we therefore explore issues that 30-year-old women
      have addressed as encouraging CCS attendance, with particular focus on aspects
      susceptible to intervention. MATERIAL AND METHODS: through the population-based
      cervical cancer screening (PCCSP) registry in Stockholm, Sweden, a stratified
      random sampling technique was used to recruit women from the same birth cohort
      with varied CCS histories and results. Nine face-to-face focus groups discussions
      (FGDs) and 30 internet-based FGDs were conducted with a total of 138 women aged
      30. Qualitative analysis was inspired by interpretative description, to generate
      clinically relevant and useful data. RESULTS: in general, these women expressed
      positive views about the PCCSP as an existing service, regardless of screening
      history. They described a wide range of factors encompassing the entire screening
      trajectory from invitation through follow-up which could motivate young women to
      CCS participation, including social marketing. Many of the suggestions related to
      individualization of the PCCSP, as well as a need to understand the relationship
      between human papilloma virus (HPV) and cervical cancer. DISCUSSION: [corrected
      these results are discussed in terms of the inherent tension between population
      based public health initiatives and individually-oriented health care provision.
      Many suggestions given are already incorporated into the existing Stockholm
      Gotland screening program, although this information may not reach women who need
      it. New research should test whether systematic information on HPV may provide a
      missing link in motivating young women to attend CCS, and which of their
      suggestions can serve to increase CCS participation.

PMID- 21091089
TI  - Granuloma annulare of the penis in a seven-year-old boy.
AB  - Subcutaneous granuloma annulare of the penis is rare, with only 10 cases in the
      world literature. This paper describes the youngest case ever reported and
      reviews its clinical features and management.

PMID- 21091088
TI  - GAD1 is a biomarker for benign and malignant prostatic tissue.
AB  - OBJECTIVE: Tissue-specific markers are useful for identification of tumour type
      in advanced cancers of unknown origin. This study investigated the expression of
      glutamate decarboxylase 1 (GAD1) in prostate and control tissue compared with the
      established prostate-specific markers prostate-specific antigen (PSA) and
      prostate-specific membrane antigen (PSMA). MATERIAL AND METHODS: A tissue
      microarray was constructed of 36 prostate adenocarcinomas, eight benign prostate
      samples and benign and malignant control tissues from urinary bladder, lung and
      rectum. Immunohistochemistry for GAD1, PSA and PSMA was performed. The products
      of staining intensity and extent were analysed. The GAD1 antibody was validated
      by Western blot. Real-time polymerase chain reaction (RT-PCR) was performed on
      malignant and benign samples from each tissue type. RESULTS: GAD1 and PSA
      immunostains were significantly stronger in malignant and benign prostatic tissue
      than in controls. PSMA was stronger in prostate cancer than in urothelial and
      rectal cancer but had a lower specificity than GAD1 and PSA. GAD1 expression
      decreased with increasing Gleason score. RT-PCR confirmed the presence of mRNA
      for GAD1, PSA and PSMA in prostate samples. CONCLUSION: GAD1 is expressed in
      benign and malignant prostatic tissue and may serve as a highly prostate-specific
      tissue biomarker.

PMID- 21091090
TI  - Incremental value of a combination of cardiac troponin T, N-terminal pro-brain
      natriuretic peptide and C-reactive protein for prediction of mortality in end
      stage renal disease.
AB  - OBJECTIVE: To determine the relative prognostic merits of C-reactive protein
      (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT
      pro-BNP) for prediction of all-cause death in patients with end-stage renal
      disease (ESRD) receiving haemodialysis. MATERIAL AND METHODS: This prospective,
      controlled cohort study included 109 patients. Biomarkers were sampled at
      inclusion and considered as categorical and continuous variables in Cox
      proportional hazard models. RESULTS: Mean follow-up +/- SD was 926 +/- 385 days,
      during which 52 patients (48%) died. All three markers were predictive of death
      in univariate analysis. In multivariable analysis, elevated cTnT (> 0.01 MUg/l)
      and CRP (> 1.0 mg/dl) remained significantly associated with mortality [hazard
      ratio (95% confidence interval), 3.2 (1.2-8.5), p = 0.017 for cTnT; 2.0 (1.0
      3.8), p = 0.032 for CRP], while NT-pro-BNP lost independent prognostic power.
      Addition of cTnT and CRP to established risk factors significantly improved the
      global fit of the model (p < 0.001), increased the c statistic from 0.726 to
      0.758 and significantly increased the integrated discrimination improvement (p <
      0.001). CONCLUSION: The results suggest that cTnT and CRP can be used in
      combination for risk stratification in patients with ESRD and highlight the
      additive effect they confer in this regard.

PMID- 21091091
TI  - Comparison of the sensitivity and specificity of urine cytology, urinary nuclear
      matrix protein-22 and multitarget fluorescence in situ hybridization assay in the
      detection of bladder cancer.
AB  - OBJECTIVE: This study aimed to compare the sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of urine cytology,
      BladderChek(r) nuclear matrix protein-22 (NMP22) and UroVysionTM fluorescence in
      situ hybridization (FISH) tests in patients with newly diagnosed bladder cancer,
      those with recurrent bladder cancer, and those with bladder cancer but in
      remission during surveillance. MATERIAL AND METHODS: Voided urine samples
      obtained from 178 patients with suspected or known bladder cancer about to
      undergo diagnostic or surveillance cystoscopy and 25 control subjects without the
      disease were divided into four and used for urine culture and cytology, NMP22
      BladderChek and UroVysion FISH tests. The sensitivity, specificity, PPV and NPV
      for each test were calculated. Comparison was made between the ability of each
      test to detect bladder cancer in the three category of patients listed. RESULTS:
      Of the 178 patients with bladder cancer, 43 were newly diagnosed, 58 had
      recurrent disease and 77 were in remission. The sensitivity of each test in newly
      diagnosed patients was: urine cytology 28%, NMP22 88% and FISH 80%; and in
      patients with recurrent disease: urine cytology 33%, NMP22 57% and FISH 85%. The
      mean specificity for urine cytology, NMP22 and FISH was 95%, 67% and 48%,
      respectively. CONCLUSION: Of the tests used in the study for detection of bladder
      cancer, NMP22 appeared to be most cost-effective and rapid, with relatively high
      sensitivity and specificity in all categories of patients. The NMP22 test may be
      considered a new gold standard for the assessment of patients with known or
      suspected bladder cancer.

PMID- 21091092
TI  - Regulation of immune-modulatory genes in left superior temporal cortex of
      schizophrenia patients: a genome-wide microarray study.
AB  - OBJECTIVES: The role of neuroinflammation in schizophrenia has been an issue for
      long time. There are reports supporting the hypothesis of ongoing inflammation
      and others denying it. This may be partly ascribed to the origin of the materials
      (CSF, blood, brain tissue) or to the genes selected for the respective studies.
      Moreover, in some locations, inflammatory genes may be up-regulated, others may
      be down-regulated. METHODS: Genome-wide microarrays have been used for expression
      profiling in post-mortem brains of schizophrenia patients. Array data have been
      analyzed by gene set enrichment analysis (GSEA) and further confirmed with
      selected genes by real-time PCR. RESULTS: In Brodman Area 22 of left superior
      temporal cortex, at least 70 genes (19%) out of 369 down-regulated genes (P <
      0.05) belonged to the immune system. 23 from those 70 genes were randomly
      selected for real-time PCR. Six reached significance level at P < 0.05.
      CONCLUSIONS: The present data support a brain-specific view of the role immune
      modulatory genes may play in the left superior temporal cortex in schizophrenia,
      because immune functions in the patients are not disturbed. In keeping with
      comparable, previous studies supporting the notion that schizophrenia is a
      disease of the synapse, we hypothesize that dysregulation of immune-related genes
      modifies synaptic functions and stability in this region.

PMID- 21091093
TI  - Polymorphisms in chemokine and receptor genes and gastric cancer risk and
      survival in a high risk Polish population.
AB  - OBJECTIVE: To examine if genetic variations in chemokine receptor and ligand
      genes are associated with gastric cancer risk and survival. METHODS: The study
      included 298 cases and 417 controls from a population-based study of gastric
      cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single
      nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor
      (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte
      DNA in relation to gastric cancer risk and survival. Genotyping was conducted at
      the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were
      computed using univariate and multivariate logistic regression models. Survival
      analysis was performed using Cox proportional hazards models. RESULTS: Gastric
      cancer risk was not associated with single chemokine polymorphisms. A CCR5
      haplotype that contained the common alleles of IVS1+151 G>T (rs2734648), IVS2+80
      C>T (rs1800024) and minor allele of IVS1+246 A>G (rs1799987) was associated with
      a borderline significantly increased risk (OR = 1.5, 95% CI: 1.0?2.2). For
      gastric cancer cases, there was a greater risk of death for carriers of the minor
      alleles of CCR2 Ex2+241 G>A (rs1799864) (HR = 1.5, 95% CI: 1.1-2.1) and CCR5
      IVS2+80 C>T (rs1800024) (HR = 1.5, 95% CI: 1.1-2.1). Carriers of the CCR5 minor
      allele of IVS1+151 G>T (rs2734648) had a decreased risk of death compared to
      homozygote carriers of the common allele (HR = 0.8, 95% CI: 0.6-1.0).
      CONCLUSIONS: Our findings do not support an association between gastric cancer
      risk and single chemokine genetic variation. The observed associations between
      cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2
      and CCR5 need replication in future studies.

PMID- 21091094
TI  - Factors associated with long-term mortality in acute pancreatitis.
AB  - BACKGROUND AND AIMS: Knowledge of the long-term prognosis of acute pancreatitis
      (AP) is limited. The aims were to investigate: (1) prognostic factors associated
      with long-term mortality in patients with AP; (2) whether or not the level of
      serum (S-)amylase at admission had an impact on the prognosis; (3) causes of
      death in these patients. METHODS: During 1977-1982, patients who were admitted to
      the five main hospitals in Copenhagen with a diagnosis of AP or chronic
      pancreatitis (CP) were included in a prospective cohort, the Copenhagen
      Pancreatitis Study (CPS); in 2008, they were followed up by linkage to the Danish
      Registries. The analyzed subcohort consisted of 352 patients with probable AP (n
      = 54) or definite AP (n = 298). RESULTS: Multivariate Cox regression analysis
      showed that significant factors associated with mortality were age, alcohol, and
      diabetes, whereas female gender, co-living and employment were associated with
      better survival. The S-amylase level had no impact on mortality. The most
      frequent causes of death were cardiovascular diseases, digestive diseases, and
      malignancies. CONCLUSIONS: Age, alcohol and diabetes had a significant impact on
      survival whereas the S-amylase level did not.

PMID- 21091096
TI  - The assessment of metabolic syndrome in UK patients with HIV using two different
      definitions: CREATE 2 study.
AB  - OBJECTIVE: To determine the prevalence and clinical associations of the metabolic
      syndrome (M-IRS) in an HIV cohort. METHODS AND DESIGN: Data was collected
      prospectively on demographics, anthropometry, HIV disease, drug regimens and
      cardiometabolic risk factors using a two-centre cross-sectional cohort study
      design. M-IRS was diagnosed by National Cholesterol Education Program (NCEP) and
      International Diabetes Federation (IDF) criteria. RESULTS: The prevalence of M
      IRS in 678 subjects was 14% by NCEP and 10% by IDF. One feature of the M-IRS was
      present in 68%, while 37% had two or more features. Increased waist circumference
      was found in 32% by NCEP or by IDF criteria, hypertriglyceridaemia in 32%,
      reduced HDL-C in 27%, 18% had raised systolic blood pressure and 13% had
      dysglycaemia. Protease inhibitor (PI) usage was similar in both M-IRS categories
      (43 vs. 38%; p = 0.38) but increased use of efavirenz was seen in M-IRS (47 vs.
      36%; p = 0.07) and nevirapine in the non-M-IRS groups (10 vs. 20%; p = 0.05).
      Multiple drug therapies were associated with raised triglyceride levels while
      nevirapine therapy was associated with raised HDL-C and abacavir with
      dysglycaemia. CONCLUSIONS: The prevalence of M-IRS in this HIV cohort was similar
      to the general population and independent of current or previous highly active
      antiretroviral therapy (HAART) or its duration. Given the relationship between
      individual drugs and features of M-IRS its significance must be interpreted in
      the light of probable accrual bias in prescribing. Prospective studies are
      required to ascertain the cardiometabolic risk factors to include in a
      prognostically useful HIV disease-specific definition of M-IRS.

PMID- 21091097
TI  - Injection-site burning and stinging in patients with rheumatoid arthritis using
      injectable biologics.
AB  - OBJECTIVE: Some patients with rheumatoid arthritis (RA) who receive injectable
      biologics experience injection-site burning and stinging (ISBS); however, the
      prevalence of ISBS in the general RA population is unknown and may impact
      preference for an injectable biologic. This study assessed the prevalence of ISBS
      and associated comorbidities in patients with RA who receive injectable
      biologics. RESEARCH DESIGN AND METHODS: The physician and patient survey
      consisted of a retrospective chart review and a prospective assessment. In the
      former, each participating US rheumatologist reviewed the medical records of five
      randomly selected RA patients receiving an injectable biologic. In the
      prospective assessment, each rheumatologist was asked to report data based on
      interviews with up to 50 RA patients currently treated with an injectable
      biologic, who were asked whether they had ISBS during or after their most recent
      injection. RESULTS: Data were analyzed for 504 patients in the retrospective
      chart review and 3326 patients in the prospective assessment; data were provided
      by 101 physicians. The overall prevalence of ISBS was 17% and 58% in the
      retrospective chart review and prospective analyses, respectively. Out of the
      1939 prospectively assessed patients who experienced at least some ISBS, 429
      (22%) rated the level of ISBS as moderate to severe (13% of total). Increased
      risk of ISBS was associated with female gender, fibromyalgia, depression, and
      more severe RA. CONCLUSIONS: The prevalence of ISBS is likely underestimated in
      many rheumatology practices. Specifically asking about it may identify patients
      who experience this side effect, provide a more accurate understanding of how
      significantly it affects them, and provide an opportunity for intervention in
      light of their preferences.

PMID- 21091098
TI  - Humanistic and economic impacts of hepatitis C infection in the United States.
AB  - OBJECTIVE: Prior research examining the effect of hepatitis C virus (HCV) on
      health-related quality of life (HRQoL) and healthcare costs is flawed because non
      patient controls were not adequately comparable to HCV patients. The current
      study uses a propensity score matching methodology to address the following
      research question: is the presence of diagnosed hepatitis C (HCV) associated with
      poorer health-related quality of life (HRQoL) and greater healthcare resource
      use? METHODS: Using data from the 2009 US National Health and Wellness Survey,
      patients who reported a HCV diagnosis (n = 695) were compared to propensity
      matched controls (n = 695) on measures of HRQoL and healthcare resource use. All
      analyses applied sampling weights to project to the US population. RESULTS: HCV
      patients reported significantly lower levels of HRQoL relative to the matched
      control group, including the physical component score (39.6 vs. 42.7, p < 0.0001)
      and health utilities (0.63 vs. 0.66, p < 0.0001). The number of emergency room
      visits (0.59 vs. 0.44, p < 0.05) and physician visits (7.7 vs. 5.9, p < 0.05) in
      the past 6 months were significantly higher for the HCV group relative to matched
      controls. CONCLUSION: The results of this study suggest that HCV represents a
      substantial burden on patients by having a significant and clinically-relevant
      impact on key dimensions of HRQoL as well as on utilization of healthcare
      resources, the latter of which would result in increased direct medical costs.
      LIMITATIONS: Due to limitations of the internet survey approach (e.g., inability
      to confirm HCV diagnosis), future research is needed to confirm these findings.

PMID- 21091099
TI  - Economic benefit of a 1-day reduction in hospital stay for community-acquired
      pneumonia (CAP).
AB  - OBJECTIVE: As a component of healthcare reform, payers, hospital administrators,
      and physicians are looking for ways to reduce hospital expenditures and improve
      efficiency. The economic benefit of a reduced hospital stay must be weighed
      against the cost of the treatment or process necessary to achieve the reduced
      length of stay (LOS). The objective of this paper was to estimate the potential
      economic benefit of a reduction in inpatient hospital LOS for a common type of
      admission, community acquired pneumonia (CAP). RESEARCH DESIGN AND METHODS: Data
      for this study were from the CAP hospital admissions selected from the 2006
      Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS).
      Potential savings associated with a 1 day reduction in CAP LOS were estimated
      using three methods: (1) average cost, (2) weighted-average incremental cost of
      an additional day, and (3) weighted-average predicted mean costs from regression
      models which were used to estimate incremental cost adjusting for hospitalization
      characteristics. MAIN OUTCOME MEASURES: Cost per day of CAP hospitalization.
      RESULTS: A total of 1,471,295 CAP admissions qualified for the analysis. The cost
      for each day of reduction in LOS in 2009 US dollars was $2273, $2373, and $2319
      for the three methods: simple average, incremental, and regression, respectively.
      Subgroup analysis and regression analysis indicated higher costs were identified:
      in patients who died in the hospital, had hospital stays in the Northeast or
      West, and in large hospitals. Longer CAP hospitalizations had a higher cost per
      additional day. Limitations include those typically associated with the use of
      administrative claims (e.g., lack of clinical detail, issues related to diagnosis
      coding). CONCLUSIONS: Eliminating a day during the course of a CAP admission is
      potentially worth $2273-2373 in economic benefits (2009 dollars). As we strive
      for greater efficiency in healthcare delivery, changes in processes and/or
      improved diagnostics or treatments may potentially achieve a reduction in the
      length of stay. The cost of such changes or improvements must be weighed against
      the economic benefit of a shorter hospitalization.

PMID- 21091103
TI  - Associations between moderate-to-vigorous physical activity and central body fat
      in 3-8-year-old children.
AB  - The aim of this study was to examine the associations between objectively
      measured moderate-to-vigorous physical activity (MVPA) and central body fat (CBF)
      indicators by anthropometry and dual energy X-ray absorptiometry (DXA) in young
      children. This study comprised 110 children aged 3-8 years. The associations
      between MVPA and CBF measures by anthropometry (waist circumference, waist-to
      height ratio, skinfold thicknesses [subscapular, suprailiac, trunk-to-extremity
      and trunk-to-total skinfold ratios] and total trunk-to-waist circumference), DXA
      (trunk fat) and a combination of both (total trunk skinfolds-to-trunk fat by DXA)
      were examined by linear regression. Levels of MVPA showed a significant inverse
      association with 8 of 9 indicators of CBF after controlling for age, gender and
      height, and fat-free mass. When total fat mass measured by DXA was included into
      the model, levels of MVPA remained significantly associated with 6 of 9
      indicators of CBF. The results highlight the plausible role of MVPA on CBF in
      young children but longitudinal studies are necessary.

PMID- 21091100
TI  - Adiposity, fitness and metabolic risk in children: a cross-sectional and
      longitudinal study.
AB  - OBJECTIVE: To better understand the early development of cardiovascular disease,
      we examined the association of adiposity measures and cardiorespiratory fitness
      (CRF) with baseline values and changes in low-grade chronic inflammation and
      insulin resistance (IR) in school children. METHODS: Eighty-three 1(st) and 5(th)
      grade children from a randomly selected control group of a physical activity
      intervention study (KISS) were prospectively studied during one academic year.
      Outcome variables included highly sensitive C-reactive protein (hs-CRP) and
      homeostasis assessment of IR (HOMA-IR). Adiposity measures included body mass
      index (BMI), waist circumference and the sum of skinfold thickness at four sites.
      CRF was assessed by the 20 m shuttle run test. All models were adjusted for age
      group, sex and pubertal group and included children who had a complete valid
      dataset for all variables. RESULTS: Baseline metabolic markers correlated
      positively with measures of adiposity and inversely with CRF (all p <= 0.02). On
      average, longitudinal changes in hs-CRP concentration increased with high
      baseline BMI in boys and skinfold thickness in both genders (both p < 0.01).
      Increases in adiposity had an additional effect on these changes (adjusted R(2)
      of the models including baseline and change in adiposity 0.49-0.53, p < 0.001).
      On the other hand, longitudinal changes in HOMA-IR were positively related to
      changes in BMI and waist circumference (p <= 0.03). Increases in HOMA-IR, but not
      in hs-CRP concentrations, were associated with low baseline CRF (p = 0.01).
      CONCLUSION: The relationship of baseline adiposity and CRF with increases in
      metabolic risk markers may have relevant implications for long-term
      cardiovascular risk. International Standard Randomised Controlled Trial Number
      (ISRCTN): TRIAL REGISTRATION: isrctn.org 15360785.

PMID- 21091104
TI  - Targeting targeted therapies.

PMID- 21091105
TI  - Regulatory T cells as potential targets for immunotherapy in inflammatory bowel
      disease.

PMID- 21091106
TI  - CYT107 enters Phase II clinical trial in HIV-infected patients.

PMID- 21091107
TI  - Immunotherapy to overcome lung tumor cell-induced escape from immunosurveillance.

PMID- 21091108
TI  - 15th International Conference on Human Antibodies and Hybridomas. 14-16 April
      2010, Tiara Park Atlantico Hotel, Porto, Portugal.
AB  - Antibodies and antibody conjugates are currently one of the largest classes of
      new drug entities under development. These versatile molecules are being
      investigated for the treatment of many pathological conditions, such as cancer
      and infectious, inflammatory and autoimmune diseases. Antibodies can exert
      biological effects as naked antibodies by themselves, or can be used as delivery
      agents conjugated with various drugs (e.g., immunoconjugates) and as tools of
      multistep targeting. Site-specific delivery of therapeutic agents has been the
      ultimate goal of the pharmaceutical industry, as it has the potential to maximize
      drug efficiency while minimizing side effects. Antibodies have much potential for
      this objective. Thus, it is useful to summarize some of the main strategies
      currently being employed for the development of these diverse therapeutic
      molecules and to highlight the recent novelties in the field. These goals were
      the focus of the 15th International Conference on Human Antibodies and
      Hybridomas, held during 14-16 April 2010 in Porto, Portugal.

PMID- 21091109
TI  - Bapineuzumab: anti-beta-amyloid monoclonal antibodies for the treatment of
      Alzheimer's disease.
AB  - In the last decade, new therapeutic approaches targeting beta-amyloid (Abeta)
      have been discovered and developed with the hope of modifying the natural history
      of Alzheimer's disease (AD). The most revolutionary of these approaches consists
      in the removal of brain Abeta via anti-Abeta antibodies. After an active vaccine
      (AN1792) was discontinued in 2002 due to occurrence of meningoencephalitis in
      approximately 6% of patients, several other second-generation active Abeta
      vaccines and passive Abeta immunotherapies have been developed and are under
      clinical investigation with the aim of accelerating Abeta clearance from the
      brain of AD patients. The most advanced of these immunological approaches is
      bapineuzumab, which is composed of humanized anti-Abeta monoclonal antibodies
      that has been tested in two Phase II trials. Bapineuzumab has been shown to
      reduce Abeta burden in the brain of AD patients. However, its preliminary
      cognitive efficacy appears uncertain, particularly in ApoE epsilon4 carriers, and
      vasogenic edema may limit its clinical use. The results of four ongoing large
      Phase III trials on bapineuzumab will provide answers regarding whether passive
      anti-Abeta immunization is able to alter the course of this devastating disease.

PMID- 21091110
TI  - Alemtuzumab in solid organ transplantation and in composite tissue
      allotransplantation.
AB  - Alemtuzumab (Campath(r), Genzyme Corporation, MA, USA) is a potent monoclonal
      antilymphocyte, anti-CD52 antibody. Since the 1980s, alemtuzumab has been used
      extensively in organ transplantation as an induction agent - also with the aim of
      avoiding or reducing maintenance immunosuppression. We herein review the
      literature on alemtuzumab in solid organ and composite tissue allotransplantation
      with an emphasis on clinical and mechanistic aspects of alemtuzumab. In summary,
      the use of alemtuzumab in solid organ and composite tissue allotransplantation
      shows excellent early results and holds potential for wider use in conjunction
      with immunosuppression minimization protocols.

PMID- 21091111
TI  - Immunotherapy through T-cell receptor gene transfer induces severe graft-versus
      host disease.
AB  - Evaluation of: Bendle GM, Linnemann C, Hooijkaas AI et al.: Lethal graft-versus
      host disease in mouse models of T cell receptor gene therapy. Nat. Med. 16(5),
      565-570 (2010). Graft-versus-host disease is commonly associated with allogeneic
      hematopoietic cell transplantation, as it is the major complication. This article
      reports that, after immunotherapy with lymphocytes that have been transduced with
      T-cell receptor (TCR) genes of known specificity, graft-versus-host disease can
      occur through TCR gene transfer. This autoimmune pathology occurs through the
      formation of self-reactive TCRs as a result of one chain of the transduced TCR
      cross-pairing with an endogenous TCR. Certain adjustments in the design of gene
      therapy vectors may help reduce the risk of such autoimmune phenomena.

PMID- 21091112
TI  - Trastuzumab (Herceptin(r)): overcoming resistance in HER2-overexpressing breast
      cancer models.
AB  - Evaluation of: Fujimoto-Ouchi K, Sekiguchi F, Yamamoto K et al.: Preclinical
      study of prolonged administration of trastuzumab as combination therapy after
      disease progression during trastuzumab monotherapy. Cancer Chemother. Pharmacol.
      66, 269-276 (2010). Trastuzumab, a humanized antibody targeted against human
      epidermal receptor (HER)2, is used in combination with chemotherapy to treat
      patients with breast cancers overexpressing HER2. Despite initial clinical
      responses, disease progresses in a significant proportion of patients treated
      with trastuzumab and chemotherapy. Evidence of resistance to trastuzumab has not
      deterred a widespread clinical practice in the treatment of metastatic breast
      cancer - at least before lapatinib entered the clinic - which consists of
      continued administration of trastuzumab in combination with another
      chemotherapeutic drug. At present, it is not known if patients benefit from this
      practice. The present preclinical study demonstrates that, in the MDA-MB-361 and
      KPL-4 HER2(+) breast cancer models, induced resistance to trastuzumab monotherapy
      can be overcome by a combination of trastuzumab and granulocyte colony
      stimulating factor or chemotherapy. The response to trastuzumab and granulocyte
      colony stimulating factor appears to involve the host's immune system and
      antibody-dependent cellular cytotoxicity. The mechanisms underlying the response
      to trastuzumab and chemotherapy remain unclear.

PMID- 21091113
TI  - Monitoring cytokine profiles during immunotherapy.
AB  - Measuring cytokine production is an integral part of measuring immune response
      during immunotherapy. Current technologies allow the simultaneous quantification
      of multiple cytokines in a variety of tissues. Patterns of cytokine response can
      be referred to as cytokine profiles. This article discusses the experimental
      design and data analysis of a number of studies that examined cytokine profiles
      in humans. We highlight potential sources of variability, both due to assay
      nuances and the diversity of human populations. We present strategies for
      analyzing data, emphasizing both multidimensional analysis and the value of
      treating each donor as his or her own control.

PMID- 21091114
TI  - Anti-TNF-alpha agents in the treatment of immune-mediated inflammatory diseases:
      mechanisms of action and pitfalls.
AB  - TNF-alpha is a potent inducer of the inflammatory response, a key regulator of
      innate immunity and plays an important role in the regulation of Th1 immune
      responses against intracellular bacteria and certain viral infections. However,
      dysregulated TNF can also contribute to numerous pathological situations. These
      include immune-mediated inflammatory diseases (IMIDs) including rheumatoid
      arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis,
      ulcerative colitis and severe chronic plaque psoriasis. Animal and human studies
      concerning the role of TNF-alpha in IMIDs have led to the development of a
      therapy based on TNF blockage. This article focuses first on the potential
      mechanisms by which the three currently licensed agents, adalimumab, etarnecept
      and infliximab, decrease the inflammatory activity of patients with different
      IMIDs. Second, it focuses on the risks, precautions and complications of the use
      of TNF-alpha inhibitors in these patients.

PMID- 21091115
TI  - Anti-alphabeta-T-cell receptor antibodies in the setting of laryngeal
      transplantation.
AB  - Inhibiting T-cell activation is critically important to the induction of
      transplantation tolerance. Monoclonal antibodies directed against the alphabeta-T
      cell receptor have been shown to cause selective immunodepletion of this T-cell
      population and can provide long-term allograft acceptance. This article discusses
      the role of this promising immunosuppressive agent in scientific research and
      clinical utilization. Specifically, the article focuses on its efficacy and
      mechanism of tolerance induction in solid tissue and composite tissue allograft
      transplantation with a particular focus on laryngeal transplantation.

PMID- 21091116
TI  - Enhancement of dendritic cells as vaccines for cancer.
AB  - Dendritic cells are the most potent antigen-presenting cells known; owing to
      their ability to stimulate antigen-specific cytolytic and memory T-cell
      responses, their use as cancer vaccines is rapidly increasing. While clinical
      trials provide evidence that dendritic cells vaccines are safe and elicit
      immunological responses in most patients, few complete tumor remissions have been
      reported and further technological advances are required. An effective dendritic
      cell vaccine must possess and maintain several characteristics: it must migrate
      to lymph nodes, have a mature, Th1-polarizing phenotype expressed stably after
      infusion and present antigen for sufficient time to produce a T-cell response
      capable of eliminating a tumor. While dendritic cells are readily matured ex
      vivo, their phenotype and fate after infusion are rarely evaluable; therefore,
      strategies to ensure that dendritic cells access lymphoid tissues and retain an
      immunostimulatory phenotype are required. In order to best exploit dendritic
      cells as vaccines, they may require genetic modification and combination with
      other strategies including adoptive T-cell transfer, inhibition of regulatory T
      cells or modulation of inflammatory pathways.

PMID- 21091118
TI  - Cost-effective immunosuppressive options for solid organ transplantation: a guide
      to lower cost for the renal transplant recipient in the USA.
AB  - Of the numerous risks associated with immunotherapy for the prevention of
      rejection, cost is perhaps the most universal. In the USA and some other
      countries, the costs of immunosuppression make transplantation unavailable for
      some medically viable transplant candidates, and for others who receive a
      transplant, the long-term costs are economically crippling. Minimization and
      tapering of immunosuppression, use of generics, manipulation of metabolism,
      infection surveillance instead of prophylaxis, and advantageous routes of
      administration are some strategies that can be employed to reduce immunotherapy
      expense. Using these strategies, we describe an immunosuppression regimen for
      kidney transplantation that might be only a third of the cost of current
      'standard' regimens in the USA. Such a regimen might allow some patients who
      might not otherwise qualify economically to safely receive a kidney transplant.
      The purpose of creating an alternative, lower-cost immunotherapy regimen is to
      give patients a choice. Responsible stewardship of scarce donor organs is the
      primary, and clearly appropriate, limiting factor.

PMID- 21091120
TI  - Occupational therapy-based and evidence-supported recommendations for assessment
      and exercises in hand osteoarthritis.
AB  - AIMS: The aims of this study were to develop recommendations for occupational
      therapy assessment and design of hand exercise programmes in patients with hand
      osteoarthritis. METHODS: An expert group followed a Delphi procedure to reach
      consensus for up to 10 recommendations for assessment and exercises,
      respectively. Thereafter, an evidence-based approach was used to identify and
      appraise research evidence supporting each recommendation, before the
      recommendations were validated by the expert group. RESULTS: The process resulted
      in 10 recommendations for assessment and eight for design of exercise programmes.
      The literature search revealed that there is a paucity of clinical trials to
      guide recommendations for hand osteoarthritis, and the evidence for the majority
      of the recommendations was based on expert opinions. Also, even if a systematic
      review demonstrates some evidence for the efficacy of strength training exercises
      in hand OA, the evidence for any specific exercise is limited to expert opinions.
      CONCLUSIONS: A first set of recommendations for assessment and exercise in hand
      osteoarthritis has been developed. For many of the recommendations there is a
      paucity of research evidence. High-quality studies are therefore needed to
      establish a high level of evidence concerning functional assessment and the
      effect of hand exercises in hand osteoarthritis.

PMID- 21091121
TI  - Senecio lamarckianus Bullock, Asteraceae.

PMID- 21091122
TI  - Antitumor activity of Sansevieria roxburghiana rhizome against Ehrlich ascites
      carcinoma in mice.
AB  - CONTEXT: Sansevieria roxburghiana Schult. & Schult. f. (Agavaceae) is a
      herbaceous perennial plant traditionally used for coughs, rheumatism; as an
      expectorant, febrifuge, purgative, and tonic. OBJECTIVE: To evaluate the
      hydroalcoholic extract of S. roxburghiana rhizome (HASR) for antitumor activity
      against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. METHODS: Twenty
      Four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, HASR
      was administered at 50 and 100 mg/kg body weight for nine consecutive days. On
      day 10 half of the mice were sacrificed and rest were kept alive for assessment
      of increase in life-span. The antitumor effect of HASR was assessed by evaluating
      tumor volume, packed cell count, viable and non-viable tumor cell count, median
      survival time and increase in life-span of EAC bearing hosts. Hematological
      profiles and serum biochemical parameters were estimated. Further, antioxidant
      properties were assessed by estimating lipid peroxidation, reduced glutathione
      (GSH), superoxide dismutase (SOD) and catalase (CAT). RESULTS AND DISCUSSION:
      HASR showed a significant (p < 0.001) decrease in tumor volume, packed cell
      volume and viable cell count and increased the life span of EAC bearing mice.
      Hematological and serum biochemical profiles were restored to normal levels in
      HASR treated mice as compared to EAC control. HASR treatment significantly (p
      <0.001) decreased lipid peroxidation and recovered GSH, SOD and CAT towards
      normal as compared to EAC control. CONCLUSION: The present study demonstrates
      that S. roxburghiana rhizome exhibited remarkable antitumor activity in Swiss
      mice that is plausibly attributable to its augmenting endogenous antioxidant
      mechanisms.

PMID- 21091123
TI  - Reliability of the school AMPS measures.
AB  - AIM: The purpose of this study was to use a variety of methods to evaluate and
      cross-validate the reliability estimates of the quality of schoolwork performance
      measures in the School Version of the Assessment of Motor and Process Skills
      (School AMPS) (1). METHODS: Split-half reliability was estimated based on School
      AMPS data from 6 194 students who had performed at least two school AMPS tasks.
      Two different split-half methods were used: splitting the School AMPS items
      vertically and splitting them horizontally. The Rasch equivalent of Cronbach's
      alpha for the full School AMPS evaluation and standard error of measurement (SEm)
      were also considered. RESULTS: All three methods yielded high reliability
      coefficient estimates (r >= 0.70) and overall SEm was low. CONCLUSIONS: From a
      practice perspective, the results of this study are of clinical importance as
      they provide evidence that occupational therapists can have confidence in the
      consistency of the School AMPS measures when they are used in the process of
      making decisions about individual students, planning interventions, and later
      performing follow-up evaluations to measure the outcome.

PMID- 21091117
TI  - Immunotherapy of systemic sclerosis.
AB  - Scleroderma is a multisystem autoimmune disease characterized by an abnormal
      immune activation associated with the development of underlying vascular and
      fibrotic disease manifestations. This article highlights the current use of drugs
      targeting the immune system in scleroderma. Nonselective immunosuppression, and
      in particular cyclophosphamide, remains the main treatment for progressing skin
      involvement and active interstitial lung disease. Mycophenolate mofetil is a
      promising alternative to cyclophosphamide. The use of cyclosporine has been
      limited by modest efficacy and serious renal toxicity. Newer T-cell (sirolimus
      and alefacept) and B-cell (rituximab)-targeted therapies have provided some
      encouraging results in small pilot studies. Hematopoietic stem cell
      transplantation can be effective for severe fibrotic skin disease, but toxicity
      remains a concern. Clinical efficacy and safety of antifibrotic treatments (e.g.,
      imatinib) await confirmation. Newer biological agents targeting key molecular or
      cellular effectors in scleroderma pathogenesis are now available for clinical
      testing.

PMID- 21091124
TI  - Women's patterns of everyday occupations and alcohol consumption.
AB  - Earlier studies on women's health and drinking and the contemporary associated
      risk factors have highlighted the need for more complex approaches in
      understanding the pathways into women's problem drinking. Research, from both
      social science and from occupational therapy models, has underlined the
      importance of deconstructing the often dichotomized way of investigating women's
      daily lives (such as in paid and unpaid work or in work and leisure) when
      discussing factors from the daily life environment and their impact on health
      issues. The aim of this study was to explore the relationship between women's
      patterns of everyday occupation and alcohol consumption using the broader concept
      of occupation from occupational therapy models. This was a cross-sectional study
      from the latest wave (2000) of a population-based project, Women and Alcohol in
      Gothenburg (WAG). The study group consisted of 851 women, aged 20-55 years. Using
      an individually oriented method, two-step clustering, three distinct patterns of
      everyday occupations were identified. Significant associations with problematic
      alcohol consumption were found in the clusters, characterized by lower engagement
      in leisure activities and a larger amount of spare time. The need for new
      preventive approaches, including investigating the importance of having engaging
      leisure activities, is discussed.

PMID- 21091125
TI  - Using MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in
      infective endocarditis: a case report of a patient with mitral valve infective
      endocarditis caused by Abiotrophia defectiva.
AB  - A case of infective endocarditis caused by Abiotrophia defectiva is presented.
      The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in
      infective endocarditis is discussed.

PMID- 21091126
TI  - Is the adiposity rebound a rebound in adiposity?
AB  - OBJECTIVE: Early adiposity rebound ([AR], when body mass index [BMI] rises after
      reaching a nadir) strongly predicts later obesity. We investigated whether the
      upswing in BMI at AR is accompanied by an increase in body fat. DESIGN: Community
      based cohort study. SUBJECTS: A total of 299 first-born children (49% male).
      Measurements. Six-monthly anthropometry and bioelectrical impedance, 4-6.5 years;
      lean and fat mass index (kg/m(2)) for direct comparison with BMI. Supplementary
      (0-2 years) weight and length measures (needed for growth curve modelling) were
      drawn from subjects' child health records. METHODS: AR was estimated from
      individually modelled BMI curves from birth to 6.5 years. Two main analyses were
      performed: 1) cross-sectional comparisons of BMI, fat mass index (FMI), lean mass
      index (LMI) and percent body fat in children with early (<5 years) and later (>5
      years) rebound; and 2) investigation of linear trends in BMI, FMI, LMI and
      percent body fat before and after AR. Results. The 81 children (27%) experiencing
      early AR had higher BMI, FMI, LMI and percent fat at 6.5 years. Overall, FMI
      decreased steeply pre-AR, at -0.56 (0.02) kg/m(2) per year (mean [Standard
      Error]), then flattened post-AR to 0.07 (0.05) kg/m(2) per year. In contrast, LMI
      increased pre-AR (0.34 [0.01]) and steepened post-AR (0.47 [0.03] kg/m(2) per
      year). CONCLUSION: The 'adiposity rebound' is characterised by increasing lean
      mass index, coupled with cessation of the decline in fat mass index.
      Understanding what controls the dynamics of childhood body composition and
      mechanisms that delay AR could help prevent obesity.

PMID- 21091127
TI  - Comparative effectiveness of colony-stimulating factors for febrile neutropenia:
      a retrospective study.
AB  - BACKGROUND: Granulocyte colony stimulating factors (G-CSFs) decrease the
      incidence of febrile neutropenia (FN) in cancer patients receiving
      myelosuppressive chemotherapy. There are two G-CSFs (pegfilgrastim and
      filgrastim) that differ in dosing schedules from which oncologists may prescribe.
      OBJECTIVES: This study aimed to compare the effectiveness of prophylactic
      pegfilgrastim and filgrastim on the risk of hospitalizations. The secondary
      objective was to compare the effectiveness of the timing of initiation
      (prophylactic versus delayed). METHODS: A retrospective study of administrative
      claims from US commercial payers included adult patients with Non-Hodgkin's
      lymphoma, breast, or lung cancer, treated with chemotherapy between July 2004 and
      January 2008. For these patients, the first course of chemotherapy and each
      unique cycle with use of G-CSF was identified and designated 'prophylaxis' if
      used within the first 5 days of each cycle, or 'delayed', if after day 5. The
      risk of neutropenia-related and all-cause hospitalization was evaluated for the
      pegfilgrastim and filgrastim prophylaxis cohorts and for the prophylaxis and
      delayed G-CSF initiation cohorts. RESULTS: Among 5,571 patient-cycles identified,
      88.9% and 11.1% used pegfilgrastim and filgrastim respectively. The rate of
      neutropenic hospitalization was 1.1% for pegfilgrastim prophylaxis and 3.5% for
      filgrastim prophylaxis (P = 0.001). Compared to chemotherapy cycles with
      filgrastim prophylaxis, those with pegfilgrastim prophylaxis had decreased risk
      of neutropenia-related (adjusted odds ratio (OR) = 0.38, 95% confidence interval
      (CI) 0.17-0.83) and all-cause hospitalization (adjusted OR = 0.51, 95% CI 0.31
      0.84). The neutropenic hospitalization rate was 1.2% for G-CSF prophylactic
      initiation and 3.7% for delayed G-CSF initiation (P < 0.001). Chemotherapy cycles
      with prophylactic initiation of either G-CSF had decreased risk of neutropenia
      related (adjusted OR = 0.34, 95% CI 0.21-0.56) and all-cause hospitalization
      (adjusted OR = 0.67, 95% CI 0.49-0.91) compared with delayed initiation of G-CSF.
      CONCLUSIONS: Pegfilgrastim prescribed as prophylaxis resulted in lower risk of
      neutropenia-related and all-cause hospitalizations compared to filgrastim
      prophylaxis. This reduction was similar for prophylactic G-CSF initiation when
      compared to delayed G-CSF initiation.

PMID- 21091129
TI  - Self-perceptions of problem-based curriculum graduates about their professional
      competency and quality of medical education.

PMID- 21091130
TI  - Do medical students agree with pharmacist-led patient self-management in Hong
      Kong?

PMID- 21091128
TI  - Scarcity or absence of humoral immune responses in the plasma and cervicovaginal
      lavage fluids of heavily HIV-1-exposed but persistently seronegative women.
AB  - To address an existing controversy concerning the presence of HIV-1-specific
      antibodies of the IgA isotype in the female genital tract secretions of highly
      exposed but persistently seronegative (HEPSN) women, 41 samples of plasma and
      cervicovaginal lavage (CVL) fluid were distributed to six laboratories for their
      blinded evaluation using ELISA with 10 different HIV-1 antigens,
      chemiluminescence-enhanced Western blots (ECL-WB), and virus neutralization. HIV
      specific IgG or IgA antibodies in plasma samples from HEPSN women were absent or
      detectable only at low levels. In CVL, 11/41 samples displayed low levels of
      reactivity in ELISA against certain antigens. However, only one sample was
      positive in two of five laboratories. All but one CVL sample yielded negative
      results when analyzed by ECL-WB. Viral neutralizing activity was either absent or
      inconsistently detected in plasma and CVL. Plasma and CVL samples from 26 HIV-1
      infected women were used as positive controls. Irrespective of the assays and
      antigens used, the results generated in all laboratories displayed remarkable
      concordance in the detection of HIV-1-specific antibodies of the IgG isotype. In
      contrast, IgA antibodies to HIV-1 antigens were not detected with consistency,
      and where present, IgA antibodies were at markedly lower levels than IgG.
      Although HIV-neutralizing activity was detected in plasma of all HIV-1-infected
      women, only a few of their CVL samples displayed such activity. In conclusion,
      frequent HIV-1 sexual exposure does not stimulate uniformly detectable mucosal or
      systemic HIV-1-specific responses, as convincingly documented in the present
      blindly performed study using a broad variety of immunological assays. Although
      HIV-1-infection leads to vigorous IgG responses in plasma and CVL, it does not
      stimulate sustained IgA responses in either fluid.

PMID- 21091132
TI  - Perceptions of cause and control in people with Parkinson's disease.
AB  - PURPOSE: This study sought to investigate how people with Parkinson's disease
      (PD) perceived both the cause and their control of the disease. METHOD: Eleven
      people living with a diagnosis of idiopathic PD in the UK were recruited via
      Parkinson's disease nurse specialists and interviewed. Interviews were
      transcribed verbatim and themes were then extracted from the transcripts using
      interpretative phenomenological analysis (IPA). Themes which were well supported
      and novel are presented. RESULTS: Three themes are presented. 1) different types
      of causal attribution; 2) perceptions of control of symptoms by medication; 3)
      the secondary control process of adaptation with particular focus on acceptance
      and denial. CONCLUSIONS: Themes of cause and control arose in a number of ways
      throughout conversations with participants. The links between cause and control
      were not universal but rather occurred in subtle individual ways. Different
      strategies were used by participants so that control could be maintained, at
      least to some extent. However, a flexible and responsive social and healthcare
      system is required to support individuals appropriately.

PMID- 21091133
TI  - Evaluation of the effect of ankle-foot orthosis use on balance and mobility in
      hemiparetic stroke patients.
AB  - We evaluated the effect of ankle-foot orthosis (AFO; articulated, plantar flexion
      stopped) use on balance and mobility in hemiparetic stroke patients in this
      study. Fifty-one hemiplegic patients who had completed the rehabilitation
      programme were included in the study. Subjects were assessed during the Ashburn
      walking and stair test, the time Up & Go test, the Berg Balance Scale (BBS) and
      the mobility subscale of the stroke rehabilitation assessment of movement
      (STREAM) in the presence and absence of AFO. The patients were asked about their
      evaluations of AFO in terms of its desirability/undesirability. All the subjects
      showed improvements in gait speed, balance and mobility with AFO use. However,
      there was no statistically significant difference between the durations of stair
      climbing with or without AFO; 45.1%% of the subjects indicated that their gait
      speed increased; 35.3%% indicated that they step on more confidently and 60.8%%
      indicated that they consider AFO unaesthetic. It was determined that the use of
      an AFO resulted in improvements in both balance and ambulation activities of
      hemiparetic patients.

PMID- 21091134
TI  - Are satisfaction with and self-management of personal assistance services
      associated with the life satisfaction of persons with physical disabilities?
AB  - PURPOSE: To examine the relationships between satisfaction with and self
      management of personal assistance services (PAS) and the quality of life (QoL) of
      persons with disabilities. To test the postulate that consumer-directed PAS can
      fulfil the human need for control and contribute to a satisfactory life. METHOD:
      A survey compared the perspectives of persons using consumer-directed PAS versus
      those using agency-directed. A Personal Data Form obtained demographics and PAS
      characteristics. The Quality of Life Inventory measured life satisfaction. A PAS
      questionnaire measured perceptions about the management of, desire for control
      of, and satisfaction with PAS. Data were analysed using SPSS(r)- 14. RESULTS:
      Significant relationships were found between QoL and satisfaction with PAS (p <
      0.001) and between perceived control of PAS and satisfaction with PAS (p <
      0.001). Significant group differences were also found. Consumer-directed
      participants reported higher satisfaction with their PAS (p < 0.01), greater
      control over services (p < 0.001) and greater QoL than agency-directed
      participants, (p = 0.001). CONCLUSIONS: The relationships found between self
      management, PAS satisfaction, and QoL support the value of consumer-directed
      programmes. Rehabilitation professionals can use this knowledge to develop,
      implement and research practises that enable self-management.

PMID- 21091136
TI  - Suicidal thinking in multiple sclerosis.
AB  - PURPOSE: Studies demonstrate that suicidal ideation (SI) is greater in persons
      with multiple sclerosis (MS) than in the general population. SI may offer some MS
      patients a mechanism for feeling in control of their lives, in the face of a
      daunting, unpredictable disease. In this study, we determined what specific
      mental constructs or perceptual themes occur for MS patients experiencing SI,
      while also examining the construct of 'control' as a central theme. METHODS:
      Individual interviews (N = 16) were audiotaped, transcribed and qualitatively
      analysed by two independent raters to test for key themes in MS patients
      reporting SI. RESULTS: In relation to SI, eight key themes were identified by
      both raters as having been expressed in interviews: perceived loss of control,
      increased family tension, loneliness, hopelessness and frustration, physical and
      psychological impact of MS, loss of perceived masculinity or femininity,
      regaining control and failure to achieve desired or expected role functioning. We
      created a model to explain the emergence of these themes as they contribute to SI
      among patients with MS. All participants indicated that perceived loss of control
      elicited thoughts of suicide. CONCLUSION: Perceived loss of control appears to be
      a major disease related burden associated with SI in MS patients.

PMID- 21091135
TI  - Towards a modified consumer haptic device for robotic-assisted fine-motor
      repetitive motion training.
AB  - PURPOSE: To develop, test and evaluate affordable haptic technology to provide
      robotic-assisted repetitive motion fine-motor training. METHODS: A haptic
      computer/user interface was modified by adding a pantograph to hold a pen and to
      increase the haptic workspace. Custom software moves a pen attached to the device
      through prescribed three-dimensional (3D) stroke sequences to create two
      dimensional glyphs. The pen's position is recorded in 3D coordinates at 1 kHz.
      Twenty-one healthy child volunteers were taught a standard handwriting curriculum
      in a group setting, two times per week for 45-60 min each session over 8 wks. The
      curriculum was supplemented by the device under the supervision of occupational
      therapy students. Outcomes were measured using the Evaluation Tool of Children's
      Handwriting (ETCH), and the Beery-Buktenica Developmental Test of visual-motor
      integration. RESULTS: Word legibility made significant gains on near point
      copying task (p=0.04; effect size=0.95). Letter legibility made no significant
      improvement. One healthy volunteer with illegible handwriting improved
      significantly on 8 of 14 ETCH measures. The children found the device engaging,
      but made several recommendations to redesign the pantograph and scribing
      movements. CONCLUSIONS: A consumer haptic device can be modified for robotic
      assisted repetitive motion training for children. The device is affordable,
      portable, and engaging. It is safe for healthy volunteers. Objective time-stamped
      data offer the potential for telerehabilitation between a remote therapist and
      the school or home.

PMID- 21091137
TI  - Identifying young children without overweight at high risk for adult overweight:
      the Terneuzen Birth Cohort.
AB  - OBJECTIVE: To develop a tool to identify children with high risk of adult
      overweight (AO), especially before developing overweight, based on body mass
      index (BMI) standard deviation score(s) (SDS) changes between 2-6 years (y) of
      age. METHODS: We fitted a linear spline model to BMI SDS of 762 young Caucasian
      adults from the Terneuzen Birth Cohort at fixed ages between birth and 18 y. By
      linear regression analysis, we assessed the increase in explained variance of the
      adult BMI SDS by adding the BMI SDS at 2 y to the models including the BMI SDS at
      4 y, 6 y and both 4 y and 6 y. AO risk was modelled by logistic regression. The
      internal validity was estimated using bootstrap techniques. Risk models were
      represented as risk score diagrams by gender for the age intervals 2-4 y and 2-6
      y. RESULTS: In addition to the BMI SDS at certain ages, the previous BMI SDS
      during childhood is positively related to adult weight. Receiver Operating Curves
      analysis provides insight into sensible cut-offs (AUC varied from 0.76 to 0.83).
      The sensitivity and specificity for 2-6 y at the cut-off of 0.25 and 0.5 are
      respectively, 0.76 and 0.74, and 0.36 and 0.93, whereas the PPV is 0.52 and 0.67,
      respectively. CONCLUSIONS: The risk score diagrams can serve as a tool for young
      children for primary prevention of adult overweight. To avoid wrongly designating
      children at risk for AO, we propose a cut-off with a high specificity at the risk
      of approximately 0.5. After external validation, wider adoption of this tool
      might enhance primary AO prevention.

PMID- 21091138
TI  - Diced cartilage rhinoplasty technique for cleft lip patients.
AB  - BACKGROUND: Late warping of dorsal cartilage onlay grafts is a problematic
      complication of current secondary rhinoplasty techniques in cleft lip patients.
      MATERIAL AND METHODS: From May 2005 to December 2008, a total of 282 cleft
      patients had a secondary rhinoplasty performed at our center with a modified
      diced cartilage technique. Finely diced cartilage was injected over a cartilage
      framework, and no "sleeve" was used. Of those patients, 246 with a follow-up of
      more than 6 months were included in this retrospective study. RESULTS: The
      infection rate was 7.7%. In addition, 5.7% of patients complained of a bulbous
      tip. Cartilage warping, as seen with classic en bloc grafting of the dorsum, did
      not occur. Dorsal irregularity was seen in 8.5% of cases, and grafts were visible
      in 1.2% of cases. The reoperation rate was 8.1%. CONCLUSION: This technique has
      greatly reduced the late cartilage warping seen with the classic cartilage bloc
      dorsal augmentation. Complications are low, comparable in occurrence to other
      techniques, and are easily manageable, making it our technique of choice.

PMID- 21091139
TI  - Urine particles analysis: performance evaluation of Sysmex UF-1000i and
      comparison among urine flow cytometer, dipstick, and visual microscopic
      examination.
AB  - INTRODUCTION: Our objective was to evaluate a newly invented urine flow
      cytometer, and select an optimal strategy for urinalysis in clinical practice.
      METHODS: The performance of UF-1000i was evaluated in both control material and
      patient samples. A total of 1631 specimens were collected and analysed by visual
      microscopy examination (VME), UF-1000i flow cytometer (Sysmex Medical Electronics
      Co, Kobe, Japan) and an automated dipstick reflectometer Clinitek Atlas (Bayer
      Corp, Elkhart, USA). RESULTS: UF-1000i showed good imprecision performance for
      the main parameters in urine particles with CV values less than 20%. The results
      from UF-1000i correlated well with VME for erythrocytes (r = 0.96), leukocytes (r
      = 0.98), and epithelial cell (r = 0.84). The area under the receiver operating
      curve (AUC) was 0.879, 0.903, 0.783, and 0.817 respectively for erythrocytes,
      leukocytes, bacteria and CAST in UF-1000i. While in Clinitek Atlas, the AUC was
      0.848, 0.803, 0.761, and 0.754 respectively. Sensitivity of combination of the
      two methods for screening remained at 98% as compared to VME alone, while
      reducing the visual review rate down to 40%. CONCLUSION: UF-1000i is capable of
      reproducible measurement of urine particles in the clinically relevant range and
      shows its advantage over Atlas. Combination of the two methods is an optimal
      strategy for urine sample screening.

PMID- 21091140
TI  - Impact of acute lymphoblastic leukemia therapy on attention and working memory in
      children.

PMID- 21091142
TI  - Nilotinib is superior to imatinib as first-line therapy of chronic myeloid
      leukemia: the ENESTnd study.
AB  - Nilotinib (Tasigna((r))) is a more potent BCR-ABL inhibitor than imatinib and was
      designed to overcome imatinib's deficiencies. Nilotinib has significant efficacy
      in patients with chronic myeloid leukemia (CML) in chronic phase, accelerated
      phase and blastic phase, following imatinib failure. Based on the results of the
      Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed
      Patients (ENESTnd) study, the US FDA has granted accelerated approval of
      nilotinib for the treatment of adult patients with newly diagnosed Philadelphia
      chromosome-positive CML in chronic phase. Imatinib has changed our perceptions of
      the therapeutic power of targeted inhibition of a pathologically active kinase.
      Nilotinib, a designer agent built on the imatinib scaffold, has proven superior
      to its template agent by every significant surrogate marker we use in monitoring
      CML. Nilotinib's clinical superiority over imatinib, as demonstrated by the
      ENESTnd study, has established it as an agent that we believe is a significant
      further step towards the cure of CML.

PMID- 21091143
TI  - ESH-SIOG International Conference on Haematological Malignancies in the Elderly.
AB  - The aging of the population has been associated with an increased incidence and
      prevalence of neoplastic diseases. The management of cancer in the older aged
      person involves novel clinical problems, including benefits and risks of
      treatment in individuals with reduced life expectancy and treatment tolerance.
      The European School of Hematology has convened the first conference on
      hematological malignancies in the elderly to explore the issues related to the
      diagnosis and the treatment of these conditions, and to provide a frame of
      reference for therapeutic decisions to practicing hematologists. The main themes
      of the conference, which was attended by hematologists and geriatricians from
      Europe and the Americas, included an operative definition of aging, the
      effectiveness and risks of antineoplastic treatment in the aged, and the
      management of common malignancies such as myelodysplasia, leukemia, myeloma and
      lymphomas.

PMID- 21091144
TI  - Hairy cell leukemia: current therapies and future directions.
AB  - Hairy cell leukemia is a rare disease for which there are multiple treatment
      options. Purine nucleoside analogs (cladribine and pentostatin) are generally
      used for front-line treatment. Other active agents include interferon, rituximab
      and, although rarely, splenectomy. In the series published by Zinzani et al. in
      Cancer, the authors conclude that initial treatment for hairy cell leukemia
      should be maximized since these patients generally enjoy the highest complete
      response rates and the longest remission durations, and subsequent lines of
      therapy have lower response rates and more frequent relapses. However, evolving
      immunohistochemical and molecular diagnostic techniques, as well as criteria for
      evaluating response to therapy and clinical trials investigating
      chemoimmunotherapy, may result in clinicians re-evaluating how patients are
      treated in the front-line and when treatment should be initiated for relapsed
      patients.

PMID- 21091145
TI  - Congenital prekallikrein deficiency.
AB  - The congenital deficiency of prekallikrein (PK) is a rare condition in which
      there is a peculiar discrepancy between a severe in vitro defect and absence of
      bleeding. The gene controlling PK synthesis is located on chromosome 4 and
      consists of 14 exons and 15 introns. Only approximately 80 cases of PK deficiency
      have been described in the literature. Owing to the lack of bleeding, most cases
      go undetected or, if detected, go unreported. Occasional bleeding or thrombosis
      have been reported in a few patients but this was only due to the presence of
      associated risk factors. It is certain that the defect does not protect from
      thrombosis. Diagnosis is based on the presence of a great prolongation of partial
      thromboplastin time and normal prothrombin time and thrombin time. The long
      partial thromboplastin time is fully corrected by the addition of normal plasma
      or normal serum and presents the unusual feature of shortening on long incubation
      times. Platelet and vascular tests are normal. Immunological studies allow
      differentiation into two types, namely cases of true deficiency, which are
      approximately 70% of the total, and cases with abnormal forms. PK is a
      glycoprotein synthesized in the liver as a single-chain peptide of 88000 Da. It
      mostly circulates (~75%) as a complex with high-molecular-weight kininogen. It is
      cleaved by FXIIa into a heavy chain and a light chain (catalytic domain), held
      together by disulfide bonds. Molecular biology techniques have so far only been
      applied to eleven families, and these studies do not yet allow definite
      phenotype/genotype conclusions. The exons involved are 5, 8, 11, 14 and 15. The
      noncoagulative effects of PK, mainly based on the effect of kallikrein, have been
      studied less, since they appear to be the result of the involvement of other
      components of the contact phase. Kallikrein can mainly affect the formation of
      bradykinin from high-molecular-weight kininogen and the activation of pro
      urokinase to urokinase. Bradykinin causes inflammation, vasodilatation and an
      increase in vessel permeability. The activation of pro-urokinase results in
      enhanced fibrinolysis. However, fibrinolysis has been reported to be normal or
      defective in these patients.

PMID- 21091146
TI  - Erythropoiesis-stimulating agents for anemic patients with cancer.
AB  - Anemia in cancer patients is common and often associated with decreased survival
      and quality-of-life scores. The introduction of erythropoiesis-stimulating agents
      (ESAs) for the treatment of anemia in patients with solid tumors and nonmyeloid
      malignancies in the 1990s has proved an important alternative to red blood cell
      transfusions. ESAs have been consistently shown to increase hemoglobin levels and
      reduce transfusion requirements in anemic cancer patients whilst also being
      associated with improvements in quality of life. Several recent studies, however,
      have raised concerns about the safety of ESAs with regards to an increased number
      of thrombo-embolic events, decreased on-study survival and possible effects of
      ESAs on tumor progression. This has led to a reappraisal of the role of ESAs in
      the treatment of anemic cancer patients. It remains generally accepted that, if
      used within current guidelines and labeling recommendations, ESAs can still be
      considered safe in patients receiving chemotherapy once individual risks are
      balanced against possible benefits.

PMID- 21091147
TI  - Acute erythroleukemia: diagnosis and management.
AB  - Acute erythroleukemia is a rare subtype of acute myeloid leukemia that has
      undergone several changes in classification over the past 30 years. There are two
      subtypes of acute erythroleukemia: the more common erythroid/myeloid subtype,
      defined by the presence of increased erythroid cells and myeloid blasts; and the
      rarer, pure erythroid subtype, characterized by expansion of immature erythroid
      cells only. The erythroid/myeloid subtype of acute erythroleukemia is closely
      related to acute myeloid leukemia with myelodysplasia-related changes, and is
      frequently characterized by morphological dysplasia and complex karyotype. Pure
      erythroleukemia is a very uncommon subtype of leukemia associated with a very
      poor response and survival to current available therapeutic agents. Treatment
      results for this disease are suboptimal and new drugs are needed. This article
      summarizes current knowledge in the field of acute erythroleukemia.

PMID- 21091148
TI  - Thromboembolic and bleeding complications in acute leukemia.
AB  - The risk of both thromboembolic and bleeding complications is high in acute
      leukemia. This double hazard has a significant negative impact on the morbidity
      and mortality of patients with this disease. The clinical manifestations of both
      complications show special features specific to the form of acute leukemia.
      Recognition of these characteristics is important in the diagnosis and management
      of acute leukemia. In this article, several additional issues are addressed,
      including the features of bleeding and thrombosis in acute promyelocytic
      leukemia, the current understanding of the leukostasis syndrome and the
      iatrogenic complications including catheter-associated thrombosis, and the
      adverse effects of therapeutic agents used in acute leukemia. As regards the
      bleeding complications, thrombocytopenia is a major cause. Corrective measures,
      including recent guidelines on platelet transfusions, are provided.

PMID- 21091149
TI  - Philadelphia chromosome-positive acute lymphoblastic leukemia in children: new
      and emerging treatment options.
AB  - Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in
      children and adolescents has, until recently, been considered one of the poorest
      risk subgroups of ALL. With chemotherapy alone, only 20-30% of children with
      Ph(+) ALL are cured. Allogeneic hematopoietic cell transplantation in first
      complete remission cures 60% of patients with a closely matched donor. Although
      targeted tyrosine kinase inhibitors (TKIs) have limited activity against Ph(+)
      ALL as a single agent, they have been evaluated in combination with chemotherapy
      with promising results. The early results of Children's Oncology Group trial
      AALL0031 have shown 88% 3-year event-free survival for Ph(+) patients treated
      with intensive chemotherapy plus continuous-dosing imatinib. This suggests that
      chemotherapy plus TKIs may be the initial treatment of choice for Ph(+) ALL in
      children. However, the numbers are small in this trial and confirmatory results
      are not yet available from the European Intergroup Study on Post Induction
      Treatment of Philadelphia Positive Acute Lymphoblastic Leukaemia with Imatinib
      trial. Additional issues include determining the most effective TKI (imatinib,
      dasatinib or nilotinib) and the most effective, least toxic chemotherapy
      backbone. The experience of adding a targeted agent such as a TKI to the standard
      chemotherapy regimen suggests that this strategy might be applied to other ALL
      subtypes to achieve both increased efficacy and decreased toxicity.

PMID- 21091150
TI  - Adult T-cell leukemia-lymphoma: current treatment strategies and novel
      immunological approaches.
AB  - Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy, closely
      associated with human T-cell lymphotropic virus type I infection. Clinically, ATL
      is classified into four subtypes: acute, lymphoma, chronic and smoldering type.
      Although the prognosis of chronic and smoldering-type ATL is relatively good,
      that of patients with acute- or lymphoma-type ATL still remains extremely poor.
      Zidovudine/IFN-alpha therapy seems to be promising, although its efficacy has not
      yet been confirmed in well-designed prospective studies. High-dose chemotherapy
      with the support of autologous transplantation does not improve outcome.
      Allogeneic stem cell transplantation is promising and approximately 40% of
      aggressive ATL patients are expected to survive long-term, although
      transplantation-related mortality is as high as 40-50%. Stem cell transplantation
      using reduced-intensity conditioning is also effective and safer, with graft
      versus-ATL and graft-versus-human T-cell lymphotropic virus type I effects
      observed after transplantation. Novel approaches including new agents such as
      purine nucleoside phosphorylase inhibitors and histone deacetylase inhibitors, or
      targeted immunotherapy using antichemokine receptor-4 antibody or dendritic
      cell/peptide vaccine are also warranted.

PMID- 21091151
TI  - Older patients with acute myeloid leukemia.
AB  - Outcomes for older patients with acute myeloid leukemia have not improved over
      the last three decades, with only a small proportion of patients achieving long
      term disease-free survival with standard induction chemotherapy. Older patients
      are more likely to have comorbidities, diminished functional reserve and other
      age-related issues, which decrease their tolerability to chemotherapy.
      Furthermore, the disease is frequently associated with poor-risk features, such
      as unfavorable cytogenetic abnormalities, antecedent hematologic disorders and
      expression of the multidrug resistant P-glycoprotein, which are associated with
      chemoresistant disease. Therefore, is it not only important to develop newer
      treatment modalities, but also to develop and validate prognostic models to help
      select the patients who are likely to benefit from and be suitable for intensive
      therapy, and reproducibly risk-stratify (based on disease biology) a relatively
      uniform group of older patients onto trials, so that the clinical significance of
      new therapeutic agents can be evaluated.

PMID- 21091152
TI  - The impact of lymphoma and treatment on male fertility.
AB  - Most patients with Hodgkin's or non-Hodgkin's lymphomas will be cured by modern
      chemotherapy and/or radiotherapy. Although some patients, especially those with
      Hodgkin's lymphoma, already have semen alterations related to their disease
      before treatment, sperm damage is mainly caused by anti-cancer treatments.
      Alkylating and similar drugs and radiation therapy are the most aggressive agents
      on male gonadal functions. Sperm damage is dependent on drug dose and individual
      sensitivity, and the recovery is unpredictable. Current approaches to fertility
      management include the exclusion of gonadotoxic agents whenever possible, in
      particular among children and preadolescent boys, and systematic sperm banking
      for all male patients, especially among adolescent patients and even in cases of
      poor sperm quality. New techniques of in vitro fertilization allow procreation
      even with poor sperm quality.

PMID- 21091154
TI  - Long-term prognostic impact of hyponatremia in the ST-elevation myocardial
      infarction.
AB  - AIMS: The aim of the study was to analyse in-hospital outcomes and long-term
      prognostic implications of reduced sodium serum level (S-Na) in the early phase
      of ST elevation myocardial infarction (STEMI) treated, primarily, with direct
      percutaneous coronary intervention (dPCI). METHODS AND RESULTS: The study
      included 218 consecutive patients (144 males, the mean age 64 +/- 13 years) with
      no history of heart failure admitted with acute STEMI. Out of them, 193 (88.5%)
      patients were treated with dPCI. The mean follow-up period was 39 +/- 21 months.
      Hyponatremia was defined as S-Na value < 135 mmol/L. A total of 72 (33%) patients
      reached hyponatremia level; 51(23.4%) of them at admission and 21 (9.6%) later
      during hospitalization. The hyponatremic patients more frequently presented with
      reduced left ventricular systolic function, Killip class III or IV and were at
      increased risk of developing cardiogenic shock compared to patients with
      normonatremia. Compared to the rest of the population, patients who developed
      hyponatremia later during hospitalization had higher incidence of acute renal
      failure; (12 patients/6.1% vs. 5 patients/25.5%, p < 0.05). The difference in
      long-term survival between the hyponatremia and normonatremia groups was
      significant (p = 0.01, log-rank test). The multiple analysis of variance
      identified decrease of S-Na levels at admission independently associated with
      total mortality (p = 0.05). CONCLUSION: Patients who developed hyponatremia in
      the early phase of STEMI were at higher risk of worse in-hospital clinical
      outcome. During the long-term follow-up, higher mortality rates were recorded in
      hyponatremic patients.

PMID- 21091155
TI  - Disruption of sphingolipid biosynthetic gene IPT1 reduces Candida albicans
      adhesion and prevents activation of human gingival epithelial cell innate immune
      defense.
AB  - We demonstrated the effect of a Candida albicans sphingolipid biosynthetic gene,
      IPT1, on the interaction between gingival epithelial and Candida cells using
      monolayer cultures and engineered human oral mucosa tissue (EHOM). Disrupting the
      IPT1 gene greatly reduced Candida adhesion to gingival epithelial cells, compared
      to the wild-type and revertant strains. The yeasts adhesion to epithelial cells
      may activate toll-like receptors (TLRs). Cell response against Candida infection
      was thus investigated by evaluating TLR expression and antimicrobial peptide
      (AMP) production. The wild-type and revertant strains both activated TLR2, TLR4,
      TLR6, and TLR9 gene expression in the epithelial cells, whereas the Deltaipt1
      mutant Candida strain had no effect on this expression. This finding was
      supported by an increased AMP expression (human beta-defensin HBD-2 and HBD-3) in
      the EHOM tissue infected with the wild-type and revertant Candida strains, and a
      decreased expression in the Deltaipt1 mutant-infected model. HBD protein
      secretion confirmed the absence of any effect by the Deltaipt1 on epithelial cell
      innate defense. This is the first study to demonstrate that a disruption of the
      IPT1 gene affects Candida-host interaction, thus preventing TLR activation and
      beta-defensin expression.

PMID- 21091156
TI  - Jiko-shisen-kyofu (fear of one's own glance), but not taijin-kyofusho (fear of
      interpersonal relations), is an east Asian culture-related specific syndrome.
AB  - OBJECTIVE: According to the DSM-IV-TR, the concept of taijin-kyofusho (fear of
      interpersonal relations) is both unique to East Asia and a culture-bound
      syndrome. In the indigenous diagnostic classification system in Japan, taijin
      kyofusho consists of four subtypes, i.e. sekimen-kyofu (phobia of blushing),
      shubo-kyofu (phobia of a deformed face/body), jiko-shu-kyofu (phobia of one's own
      foul body odour), and jiko-shisen-kyofu (phobia of one's own glance). Each
      subtype except for phobia of one's own glance can be adequately assigned to a
      respective existing category in the DSM-IV-TR. The aim of the study was to
      introduce clinical features of phobia of one's own glance to western
      psychiatrists. METHODS: Description of a series of cases with jiko-shisen-kyofu
      (phobia of one's own glance). RESULTS: All of our cases shared the unique feature
      that they suffered from the preoccupation that their own glance was offensive to
      others, and as a result were socially withdrawn themselves. CONCLUSIONS: To our
      best knowledge, no cases with a clear picture of phobia of one's own glance have
      been reported in the West to date. The controversial issue of the classification
      of phobia of one's own glance as an east Asian culture-related specific syndrome
      was addressed.

PMID- 21091157
TI  - Pyrenophora bromi, causal agent of brownspot of bromegrass, expresses a gene
      encoding a protein with homology and similar activity to Ptr ToxB, a host
      selective toxin of wheat.
AB  - Ptr ToxB, encoded by ToxB, is one of multiple host-selective toxins (HST)
      produced by the wheat pathogen Pyrenophora tritici-repentis. Homologs of ToxB are
      found in several ascomycetes, including sister species Pyrenophora bromi, causal
      agent of brownspot of bromegrass. Due to the close evolutionary relatedness of P.
      tritici-repentis and P. bromi and that of their grass hosts, we hypothesized that
      homologs of ToxB in P. bromi may act as HST in the disease interaction between P.
      bromi and bromegrass. A representative set of transcriptionally active P. bromi
      ToxB genes were heterologously expressed in Pichia pastoris and the resultant
      proteins tested for their ability to act as HST on bromegrass. The tested
      Pyrenophora bromi ToxB (Pb ToxB) proteins were not toxic to bromegrass; thus, Pb
      ToxB does not appear to function as an HST in the P. bromi-bromegrass
      interaction. Instead, we revealed that the Pb ToxB proteins can be toxic to Ptr
      ToxB-sensitive wheat, at levels similar to Ptr ToxB, and the corresponding P.
      bromi ToxB genes are expressed in P. bromi-inoculated wheat. Our data suggest
      that P. bromi possesses the potential to become a wheat pathogen and highlights
      the importance of investigating the interaction between P. bromi and wheat.

PMID- 21091158
TI  - Light quantity and photosystem function mediate host susceptibility to Turnip
      mosaic virus via a salicylic acid-independent mechanism.
AB  - Evidence going as far back as the early part of the 20th century suggests that
      both light and chloroplast function may play key roles in host susceptibility to
      viruses. Despite the long history of such work, confirmation of these phenomena
      and a determination of the underlying mechanisms remain elusive. Here, we
      revisited these questions using modern imaging technologies to study the
      susceptibility of Nicotiana benthamiana to Turnip mosaic virus (TuMV). We found
      that both light deficiency and photosystem impairment increased the
      susceptibility of N. benthamiana to TuMV infection. Time-lapse photography
      studies indicated that, under these conditions, rub-inoculated plants exhibited
      greater numbers of infection foci and more rapid foci development. The rate of
      systemic movement was also accelerated though cell-to-cell movement appeared
      unchanged. Inhibition of salicylic acid (SA)-mediated defense responses is not
      likely responsible for changes in susceptibility because SA and pathogen response
      1 gene induction were not affected by light deficiency or chloroplast impairment
      and treatment of plants with SA had no measureable impact on TuMV infection.
      Taken together, these data suggest that both light and optimal chloroplast
      function influence virus infection either by limiting the cellular resources
      needed by TuMV to establish replication complexes or the host's ability to
      activate SA-independent defenses.

PMID- 21091159
TI  - Endophytic Trichoderma isolates from tropical environments delay disease onset
      and induce resistance against Phytophthora capsici in hot pepper using multiple
      mechanisms.
AB  - Endophytic Trichoderma isolates collected in tropical environments were evaluated
      for biocontrol activity against Phytophthora capsici in hot pepper (Capsicum
      annuum). Six isolates were tested for parasitic and antimicrobial activity
      against P. capsici and for endophytic and induced resistance capabilities in
      pepper. Isolates DIS 70a, DIS 219b, and DIS 376f were P. capsici parasites, while
      DIS 70a, DIS 259j, DIS 320c, and DIS 376f metabolites inhibited P. capsici. All
      six isolates colonized roots but were inefficient stem colonizers. DIS 259j, DIS
      320c, and DIS 376f induced defense-related expressed sequence tags (EST) in 32
      day-old peppers. DIS 70a, DIS 259j, and DIS 376f delayed disease development.
      Initial colonization of roots by DIS 259j or DIS 376f induced EST with potential
      to impact Trichoderma endophytic colonization and disease development, including
      multiple lipid transferase protein (LTP)-like family members. The timing and
      intensity of induction varied between isolates. Expression of CaLTP-N, encoding a
      LTP-like protein in pepper, in N. benthamiana leaves reduced disease development
      in response to P. nicotianae inoculation, suggesting LTP are functional
      components of resistance induced by Trichoderma species. Trichoderma isolates
      were endophytic on pepper roots in which, depending on the isolate, they delayed
      disease development by P. capsici and induced strong and divergent defense
      reactions.

PMID- 21091160
TI  - Identification and validation of reference genes for normalization of transcripts
      from virus-infected Arabidopsis thaliana.
AB  - Real-time quantitative polymerase chain reaction (qPCR) of complementary DNA is
      now a standard method for studies of gene expression. However, qPCR can identify
      genuine variation only when transcript quantities are accurately normalized to an
      appropriate reference. To identify the most reliable reference genes for
      transcript quantification by qPCR, we describe a systematic evaluation of
      candidate reference genes of Arabidopsis thaliana ecotype Columbia-0 (Col-0).
      Twelve genes were selected for transcript stability studies by qPCR of
      complementary DNA prepared from Arabidopsis leaf tissue infected with one of five
      plant viruses (Cauliflower mosaic virus, Tobacco mosaic virus, Tomato spotted
      wilt virus, Turnip mosaic virus, and Turnip yellow mosaic virus). The F-box
      family protein, elongation factor 1-alpha, sand family protein, and protodermal
      factor 2 gene transcripts showed the most stable accumulation, whereas a
      traditionally used reference gene, Actin8, showed the least stable accumulation
      as measured by the geNorm algorithm. The data furnish plant virologists with
      reference genes for normalization of qPCR-derived gene expression in virus
      infected Arabidopsis and will be beneficial to the selection and design of
      primers targeting orthologous genes in other plant species.

PMID- 21091161
TI  - Peptidoglycan biosynthesis machinery: a rich source of drug targets.
AB  - The range of antibiotic therapy for the control of bacterial infections is
      becoming increasingly limited because of the rapid rise in multidrug resistance
      in clinical bacterial isolates. A few diseases, such as tuberculosis, which were
      once thought to be under control, have re-emerged as serious health threats.
      These problems have resulted in intensified research to look for new inhibitors
      for bacterial pathogens. Of late, the peptidoglycan (PG) layer, the most
      important component of the bacterial cell wall has been the subject of drug
      targeting because, first, it is essential for the survivability of eubacteria and
      secondly, it is absent in humans. The last decade has seen tremendous inputs in
      deciphering the 3-D structures of the PG biosynthetic enzymes. Many inhibitors
      against these enzymes have been developed using virtual and high throughput
      screening techniques. This review discusses the mechanistic and structural
      properties of the PG biosynthetic enzymes and inhibitors developed in the last
      decade.

PMID- 21091163
TI  - History of oral contraception.
AB  - On the 50th birthday of the pill, it is appropriate to recall the milestones
      which have led to its development and evolution during the last five decades. The
      main contraceptive effect of the pill being inhibition of ovulation, it may be
      called a small miracle that this drug was developed long before the complex
      regulation of ovulation and the menstrual cycle was elucidated. Another stumbling
      block on its way was the hostile climate with regard to contraception that
      prevailed at the time. Animal experiments on the effect of sex steroids on
      ovulation, and the synthesis of sex steroids and orally active analogues were the
      necessary preliminaries. We owe the development of oral contraceptives to a
      handful of persons: two determined feminists, Margaret Sanger and Katherine
      McCormick; a biologist, Gregory Pincus; and a gynaecologist, John Rock. Soon
      after the introduction of the first pills, some nasty and life-threatening side
      effects emerged, which were due to the high doses of sex steroids. This led to
      the development of new preparations with reduced oestrogen content, progestins
      with more specific action, and alternative administration routes. Almost every
      decade we have witnessed a breakthrough in oral contraception. Social and moral
      objections to birth control have gradually disappeared and, notwithstanding some
      pill scares, oral contraceptives are now one of the most used methods of
      contraception. Finally, all's well that ends well: recent reports have
      substantiated the multiple noncontraceptive health benefits paving the way for a
      bright future for this 50-year-old product.

PMID- 21091162
TI  - Emotion regulation and substance use frequency in women with substance dependence
      and borderline personality disorder receiving dialectical behavior therapy.
AB  - BACKGROUND: Dialectical behavior therapy (DBT) identifies emotion dysregulation
      as central to the dangerous impulsivity of borderline personality disorder (BPD)
      including substance use disorders, and DBT targets improved emotion regulation as
      a primary mechanism of change. However, improved emotion regulation with DBT and
      associations between such improvement and behavioral outcomes such as substance
      use has not been previously reported. OBJECTIVE: Thus, the goal of this study was
      to assess for improvement in emotion regulation and to examine the relationship
      between improvements in the emotion regulation and substance use problems
      following DBT treatment. METHOD: Emotion regulation as assessed by the
      Difficulties in Emotion Regulation Scale, depressed mood as assessed by the Beck
      Depression Inventory, and their associations with substance use frequency were
      investigated in 27 women with substance dependence and BPD receiving 20 weeks of
      DBT in an academic community outpatient substance abuse treatment program.
      RESULTS: Results indicated improved emotion regulation, improved mood, and
      decreased substance use frequency. Further, emotion regulation improvement, but
      not improved mood, explained the variance of decreased substance use frequency.
      CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This is the first study to demonstrate
      improved emotion regulation in BPD patients treated with DBT and to show that
      improved emotion regulation can account for increased behavioral control in BPD
      patients. SIGNIFICANCE AND FUTURE RESEARCH: Emotion regulation assessment is
      recommended for future studies to further clarify the etiology and maintenance of
      disorders associated with emotional dysregulation such as BPD and substance
      dependence and to further explore emotion regulation as a potential mechanism of
      change for clinical interventions.

PMID- 21091164
TI  - Efficacy of contraceptive methods: a review of the literature.
AB  - OBJECTIVES: To provide a comprehensive and objective summary of contraceptive
      failure rates for a variety of methods based on a systematic review of the
      literature. METHODS: Medline and Embase were searched using the Ovid interface
      from January 1990 to February 2008, as well as the reference lists of published
      articles, to identify studies reporting contraceptive efficacy as a Pearl Index
      or life-table estimate. Reports that recruited less than 400 subjects per study
      group and those covering less than six cycles/six months were excluded. In
      addition, unlicensed products or those not internationally available, emergency
      contraception, and vasectomy studies were excluded. RESULTS: Information was
      identified and extracted from 139 studies. One-year Pearl Indices reported for
      short-acting user-dependent hormonal methods were generally less than 2.5. Gross
      life-table rates for long-acting hormonal methods (implants and the
      levonorgestrel releasing-intrauterine system [LNG-IUS]) generally ranged between
      0-0.6 per 100 at one year, but wider ranges (0.1-1.5 per 100) were observed for
      the copper intrauterine devices (0.1-1.4 per 100 for Cu-UIDs with surface area >=
      300 mm2 and 0.6-1.5 per 100 for those with surface area < 300 mm2). Barrier and
      natural methods were the least effective. CONCLUSIONS: Our review broadly
      confirms the hierarchy of contraceptive effectiveness in descending order as: (1)
      female sterilisation, long-acting hormonal contraceptives (LNG-IUS and implants);
      (2) Cu-IUDs with >= 300 mm2 surface area; (3) Cu-IUDs with < 300 mm2 surface area
      and short-acting hormonal contraceptives ( injectables, oral contraceptives, the
      patch and vaginal rings), (4) barrier methods and natural methods.

PMID- 21091165
TI  - New regimens with combined oral contraceptive pills--moving away from traditional
      21/7 cycles.
AB  - The practice of extending combined oral contraceptive use (COC) and eliminating
      or reducing the hormone free interval has been in use for many years. More
      recently a range of products with new dosing options has been developed and
      marketed. Women and physicians in developed countries are comfortable with and
      many prefer the use of extended COC regimens which provide an option to eliminate
      or reduce the frequency of regular withdrawal bleeding. The extension of active
      pill taking and the reduction or elimination of the hormone-free interval have
      been shown to be beneficial for women who experience menstrual cycle-related
      problems such as heavy bleeding or dysmenorrhoea. The hormone-free interval of
      less than seven days has additional benefits in managing hormone withdrawal
      symptoms and efficacy may be improved in situations where pills are inadvertently
      missed or in women who are perceived as 'poor' pill takers. This paper provides a
      descriptive review highlighting the development of new dosing options that alter
      the traditional 21/7 COC regimen. The rationale for and the acceptability of COCs
      developed with alternative dosing regimens is examined.

PMID- 21091166
TI  - Contraceptive use and behavior in the 21st century: a comprehensive study across
      five European countries.
AB  - OBJECTIVE: The choice of currently available contraceptive methods has increased
      considerably in recent years, offering women of reproductive age a variety of
      different methods dependent on their needs and lifestyle. In order to determine
      the pattern of use of current methods in contraception, a survey was conducted in
      a large population of women drawn from five European countries (France, Germany,
      Italy, Spain and the United Kingdom). METHOD: More than 12,000 randomly selected
      women, aged 15-49 years, were interviewed using a standardized questionnaire
      which addressed the use of current methods of contraception. The responses were
      analyzed for the total study population, and, where appropriate, by country and
      age. RESULTS: An oral contraceptive (OC) was confirmed as the most widely used
      method of contraception for women in the European study population, with an
      estimated 22 million users in the five countries. Women using an OC reported very
      high levels of satisfaction (>90%). Male and female sterilization were the main
      methods of contraception in women aged 40 years and older. One-half of the women
      had undergone their sterilization before the age of 35 years. More than 50% of
      the women who had undergone sterilization had not been adequately informed and
      counselled about alternative reversible contraceptive options. No method of
      contraception was being used currently by 23% of the European study population,
      and unreliable methods of contraception (including cap/diaphragm, chemical, and
      natural and withdrawal methods) were being used by a further 6% of the
      population. Although valid reasons (e.g. not in a sexual relationship, wish to
      become pregnant) were given by many women who were not using contraception, there
      still remains a large number of women who need counselling regarding the
      importance of using reliable contraceptive methods. The number of women aged 15
      49 years in the five European countries who are considered at risk of an unwanted
      pregnancy is estimated to be 4.7 million (6.5%). CONCLUSIONS: Differences in the
      use pattern of contraceptive methods were demonstrated that emphasize the social
      and cultural differences between the countries. The findings in the current study
      can be used as a baseline from which to monitor trends in contraceptive use and
      behavior in subsequent studies.

PMID- 21091168
TI  - What do we know about sexual and reproductive health of adolescents in Europe?
AB  - OBJECTIVES: Acceptance of sexual and reproductive health as fundamental to the
      sustainable development of societies has allowed for creation of new reproductive
      health programmes and policies. WHO sexual and reproductive health (SRH)
      strategies were developed in the WHO Regional Office for Europe (2001), as well
      as globally (2004). Adolescent SRH is important in both strategies. Despite these
      commitments, adolescents remain vulnerable to poor reproductive health. The goal
      of this paper is to analyse the current status of SRH of adolescents in Europe.
      METHODS: Key reproductive health indicators were chosen. Information was obtained
      from published studies, databases and questionnaires sent to WHO reproductive
      health counterparts within the health ministries in the Member States of the WHO
      European Region. RESULTS: Pregnancy rate, age at first sexual intercourse,
      contraceptive use at first and last intercourse, contraceptive prevalence, HIV
      knowledge, and STI rates vary widely according to the population considered.
      Gender difference and lack of information pertaining to SRH of all adolescent
      populations are other key findings. CONCLUSIONS: While the SRH of most European
      adolescents is good, they remain a vulnerable population. Lack of standardized
      reproductive indicators and age specific aggregate data make it difficult to
      accurately assess the situation in individual countries or perform cross country
      comparison.

PMID- 21091169
TI  - 50th anniversary of the pill--what does this story teach us?

PMID- 21091170
TI  - Brave and angry--the creation and development of the International Planned
      Parenthood Federation (IPPF).
AB  - This paper looks back on the developments in thinking from birth control, through
      voluntary family planning, to a comprehensive approach to sexual and reproductive
      health and rights (SRHR), and celebrates some of the key players in this
      evolution. It tells the story of the creation of the International Planned
      Parenthood Federation (IPPF) in 1952, and scrutinises how important this
      organisation was then and is now. It gives an idea of the efforts it took to
      reassemble initiatives around the world into one body, strong enough to foster
      the cause to the benefit of all. While IPPF was and still is a unique
      association, it has increased its partnerships and works together with a
      multitude of organisations active in the field of SRHR. In the current political
      context joint efforts are still needed to protect the universally recognised
      human right of people to decide freely and responsibly on the number and spacing
      of their children, and their access to adequate education and information.

PMID- 21091171
TI  - Contraceptive use, fertility, and unsafe abortion in developing countries.
AB  - OBJECTIVES: Despite a substantial rise in contraceptive use around the world,
      unplanned pregnancies and induced abortion continue to occur. Each year an
      estimated 19 million abortions are carried out outside the legal system, often by
      unskilled practitioners or under unhygienic conditions. This paper explores the
      relationship between contraceptive prevalence and unsafe abortion in developing
      regions with different levels of fertility. These relationships manifest the
      extent to which the desire to regulate fertility is addressed by contraception or
      by unsafe abortion, where access to safe abortion is legally restricted. METHODS:
      Secondary analysis of estimates of unsafe abortion, total fertility rate and
      contraceptive prevalence, by geographical regions. RESULTS: High levels of unsafe
      abortion persist even where contraceptive prevalence is increasing and fertility
      is declining. It appears that a high dependence on sterilization for limiting
      family size may by be preceded by reliance on unsafe abortion, where abortion is
      restricted, for birth spacing. CONCLUSIONS: The reliance on unsafe abortion could
      be reduced during fertility transition by improving women's access to reversible
      contraceptives for spacing births as well as to sterilization for terminating
      childbearing. Expanding contraceptive choices and a balanced method mix can serve
      as an effective strategy to prevent unsafe abortion where reliance on
      sterilization to limit childbearing is not preceded by the use of reversible
      modern methods for spacing and where access to safe abortion is restricted by
      law. The intriguing association between contraceptive method choice and the
      incidence of unsafe abortion deserves further exploration.

PMID- 21091172
TI  - After 50 years of ethinylestradiol, another oestrogen in combined oral
      contraceptives.

PMID- 21091174
TI  - Effects of alcohol consumption on iron metabolism.
AB  - BACKGROUND/OBJECTIVES: Patients with alcohol abuse frequently suffer from
      malnutrition which may result in insufficient iron distribution and iron overload
      or deficiency. Iron metabolism can be described by a combination of biochemical
      soluble transferrin receptor, ferritin, C-reactive protein (CRP), and
      hematological parameters. Here, vitamin B12 and folic acid state were assessed.
      Results on iron metabolism in patients with alcohol dependence in comparison with
      social drinkers are presented. MATERIALS/METHODS: Samples from 101 patients with
      dependent alcohol consumption were included. The control group comprised 115
      social drinkers. Inclusion criteria for patients with chronic regular
      drinking/social drinkers were positive/negative score of the Alcohol Use
      Disorders Identification Test (AUDIT), and positive/negative score for alcohol
      abuse/dependence (DSM-IV criteria). RESULTS: Absolute values for ferritin and
      sTfR are increased in patients with alcohol dependence with current consumption
      (ALC) compared with social drinkers. No major differences are observed in the
      ratio of sTfR/log ferritin in comparison with social drinkers. Hemoglobin
      concentrations correlated between the two groups. Mean corpuscular volume (MCV)
      was significantly increased in the ALC collective compared to social drinkers.
      Eighty patients of the alcohol-dependent group had sufficient iron repletion, 11
      had iron overload, 6 are suspicious for functional iron deficiency, and 4 are
      suspicious for reduced iron supply. No vitamin B12/folate deficiencies are
      observed in alcohol-dependent patients. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:
      No major abnormalities of iron metabolism are seen in patients with chronic
      alcohol ingestion besides the well-known macrocytic anemia. Iron overload is
      relatively frequent and observed in 9% of cases. No differences in vitamin B12
      and folate levels were found between individuals with alcohol dependence and
      social drinkers.

PMID- 21091175
TI  - Female sterilisation is becoming less popular.

PMID- 21091176
TI  - Reproductive and contraceptive issues in chronically ill adolescents.
AB  - OBJECTIVES: To address reproductive and contraceptive issues in adolescent girls
      with chronic medical conditions in order to assist health-care providers when
      they counsel teenagers about contraceptive methods. METHODS: The review is based
      on a literature search in Medline (1973-2010) about specific contraceptive use by
      adolescents with obesity, endocrine, cardiovascular, haematologic, oncologic,
      neurological, psychiatric, gastrointestinal, hepatobiliary, autoimmune, renal,
      pulmonary conditions and disabilities. The latest recommendations from the World
      Health Organisation for adolescents are also added. Contraceptive methods studied
      were combined hormonal contraceptives, progestogen-only contraceptives, and
      intrauterine contraceptives. RESULTS: Adolescents are eligible to use any method
      of contraception. Contraceptive choices of chronically ill adolescents have
      changed over time. Given new developments in the field of adolescent sexual and
      reproductive health care, safe and effective forms of contraception are available
      for almost every adolescent with a chronic condition. When selecting a method,
      the nature of the medical illness and the expressed desires of the teenager must
      be taken into account. CONCLUSIONS: Adolescents, including those with chronic
      conditions, are sexual beings; they are entitled to sexual and reproductive
      health care. Decisions on appropriate contraception must be based upon informed
      choice, after adequate sexual health education.

PMID- 21091177
TI  - Physical activity and sexuality in perimenopausal women.
AB  - OBJECTIVES: To determine if there is a link between physical activity and sexual
      functioning in perimenopausal women, by comparing groups of women with low,
      moderate and high physical activity levels with regard to selected domains of
      their sexual functioning. METHODS: The research involved 400 healthy Polish
      women, aged 45-55 years. The final analysis encompassed 336 women who fulfilled
      all the inclusion criteria. The research tool was a two-part questionnaire. The
      first part covered the socio-economic status, patient history, and gynaecological
      obstetric history. Part two consisted of an extended version of the International
      Physical Activity Questionnaire long form, evaluating the level of physical
      activity over the last seven days, and the Female Sexual Function Index. RESULTS:
      The mean age of the respondents was 50.56 +/- 2.33 years. The analysis showed
      statistically significant differences between all the domains of physical
      activity and the FSFI of the studied women. In the group of women without sexual
      disorders, respondents with a low physical activity level in all questionnaire
      domains were the least numerous. CONCLUSIONS: In perimenopausal women an
      association is seen between high levels of general physical activity and better
      sexual functioning.

PMID- 21091178
TI  - Consumption of combined oral contraceptives and venous thromboembolism in Zagreb,
      Croatia.

PMID- 21091180
TI  - Effect of obesity on asthma phenotype is dependent upon asthma severity.
AB  - BACKGROUND: We recently reported that obese and non-obese patients with asthma
      have similar airflow limitation and bronchodilator responsiveness, but obese
      patients have more symptoms overall. There is limited information on the effect
      of obesity on asthmatics of varying severity measured by objective physiological
      parameters. Understanding how obesity affects asthmatics of differing severity
      can provide insights into the pathogenesis of asthma in the obese and a rationale
      for the therapeutic approach to such patients. METHODS: Participants with asthma
      from two American Lung Association--Asthma Clinical Research Center (ALA-ACRC)
      studies were grouped by tertiles of airflow obstruction (forced expiratory volume
      in one second (FEV(1)%) predicted, FEV(1)/forced vital capacity (FVC)) and
      methacholine reactivity (PC(20)FEV(1)). Within each tertile, we examined the
      independent effect of body mass index (BMI), divided into normal weight,
      overweight, and obese categories, on lung function, airway reactivity, and
      symptoms. RESULTS: Overall, both FEV(1) and FVC decreased and symptoms worsened
      with increasing BMI; airway reactivity was unchanged. When stratified by the
      degree of airflow obstruction, higher BMI was not associated with greater airway
      reactivity to methacholine. Higher BMI was associated with more asthma symptoms
      only in the least obstructed FEV(1)/FVC tertile. When stratified by degree of
      airway reactivity, BMI was inversely associated with FVC in all PC(20)FEV(1)
      tertiles. BMI was directly associated with asthma symptoms only in those with the
      least airway reactivity. CONCLUSIONS: Obesity does not influence airway
      reactivity in patients with asthma and it is associated with more symptoms only
      in those with less severe disease.

PMID- 21091181
TI  - New virulence groups in Fusarium oxysporum f. sp. phaseoli: the expression of the
      gene coding for the transcription factor ftf1 correlates with virulence.
AB  - Fusarium oxysporum f. sp. phaseoli strains isolated from runner bean plants
      showing Fusarium wilt symptoms were characterized. The analysis of the genetic
      diversity of these strains and the comparison with strains formerly isolated from
      diseased common bean plants grown in the same region of Spain indicated a close
      genetic similarity among them. Pathogenicity assays carried out on runner bean
      plants showed virulence differences that allowed the classification of these
      strains into three groups: super virulent, highly virulent, and weakly virulent.
      However, all the analyzed strains behaved as highly virulent when inoculated on
      common bean plants, indicating that virulence is specific of the host-pathogen
      interaction. We also analyzed the number of copies and expression of the gene
      encoding the transcription factor ftf1, which has been shown to be specific of
      virulent F. oxysporum strains and highly up-regulated during plant infection. In
      planta real-time quantitative polymerase chain reaction expression analysis
      showed that expression of ftf1 was correlated with the degree of virulence. The
      comparative analysis of the polymorphic copies of ftf1 detected in the strains
      here characterized and those detected in the genome sequence of F. oxysporum f.
      sp. lycopersici strain 4287 indicates that some of the copies are likely
      nonfunctional.

PMID- 21091182
TI  - Decision aids for multiple-decision disease management as affected by weather
      input errors.
AB  - Many disease management decision support systems (DSSs) rely, exclusively or in
      part, on weather inputs to calculate an indicator for disease hazard. Error in
      the weather inputs, typically due to forecasting, interpolation, or estimation
      from off-site sources, may affect model calculations and management decision
      recommendations. The extent to which errors in weather inputs affect the quality
      of the final management outcome depends on a number of aspects of the disease
      management context, including whether management consists of a single dichotomous
      decision, or of a multi-decision process extending over the cropping season(s).
      Decision aids for multi-decision disease management typically are based on simple
      or complex algorithms of weather data which may be accumulated over several days
      or weeks. It is difficult to quantify accuracy of multi-decision DSSs due to
      temporally overlapping disease events, existence of more than one solution to
      optimizing the outcome, opportunities to take later recourse to modify earlier
      decisions, and the ongoing, complex decision process in which the DSS is only one
      component. One approach to assessing importance of weather input errors is to
      conduct an error analysis in which the DSS outcome from high-quality weather data
      is compared with that from weather data with various levels of bias and/or
      variance from the original data. We illustrate this analytical approach for two
      types of DSS, an infection risk index for hop powdery mildew and a simulation
      model for grass stem rust. Further exploration of analysis methods is needed to
      address problems associated with assessing uncertainty in multi-decision DSSs.

PMID- 21091183
TI  - A single dominant locus, ren4, confers rapid non-race-specific resistance to
      grapevine powdery mildew.
AB  - In the present study we screened the progeny of Vitis vinifera * V. romanetii
      populations segregating for resistance to powdery mildew and determined the
      presence of a single, dominant locus, Ren4, conferring rapid and extreme
      resistance to the grapevine powdery mildew fungus Erysiphe necator. In each of
      nine Ren4 pseudo-backcross 2 (pBC(2)) and pBC(3) populations (1,030 progeny),
      resistance fit a 1:1 segregation ratio and overall segregated as 543 resistant
      progeny to 487 susceptible. In full-sib progeny, microscopic observations
      revealed the reduction of penetration success rate (as indicated by the emergence
      of secondary hyphae) from 86% in susceptible progeny to below 10% in resistant
      progeny. Similarly, extreme differences were seen macroscopically. Ratings for
      Ren4 pBC(2) population 03-3004 screened using natural infection in a California
      vineyard and greenhouse and using artificial inoculation of an aggressive New
      York isolate were fully consistent among all three pathogen sources and
      environments. From 2006 to 2010, Ren4 pBC(2) and pBC(3) vines were continuously
      screened in California and New York (in the center of diversity for E. necator),
      and no sporulating colonies were observed. For population 03-3004, severity
      ratings on leaves, shoots, berries, and rachises were highly correlated (R(2) =
      0.875 to 0.996) in the vineyard. Together, these data document a powdery mildew
      resistance mechanism not previously described in the Vitaceae or elsewhere, in
      which a dominantly inherited resistance prevents hyphal emergence and is non-race
      specific and tissue-independent. In addition to its role in breeding for durable
      resistance, Ren4 may provide mechanistic insights into the early events that
      enable powdery mildew infection.

PMID- 21091184
TI  - Explaining loss caused by tomato spotted wilt virus on tobacco with boreal winter
      weather: a Bayesian approach.
AB  - In North Carolina, Tomato spotted wilt virus (TSWV) has regularly been reported
      since 1997, with incidence being the highest in 2002. At the end of each season,
      a questionnaire is sent to the county agents to report disease losses. TSWV
      reported losses in 1993 to 2007 from 58 counties were available. A county-year
      combination was considered a case and, in total, 494 cases were analyzed. The
      winter months' temperature and precipitation significantly explained the reported
      TSWV loss (R(2) = 0.82). Specifically, the monthly average air temperature for
      December to February had a positive association with TSWV loss (P < 0.0001)
      whereas the total precipitation for the same months had a negative effect (P <
      0.0001). Bayesian hierarchical models were implemented to include spatial and
      nonspatial random effects to investigate if there were significant spatial
      correlations or unexplained variability, respectively, and, thus, other
      significant variables that were ignored in the model development. The spatial
      random effects were not significant but the nonspatial random effects were
      significant in 36 cases. The importance of spring weather to dispersal of thrips
      and TSWV has been previously identified. Winter weather also may be a good
      indicator of potential available TSWV inoculum for the upcoming season.

PMID- 21091185
TI  - Effect of lacidipine pre-treatment on diabetic neuropathy in rats.
AB  - OBJECTIVE: The present study was planned to evaluate the effects of lacidipine on
      STZ induced diabetic neuropathy. MATERIAL AND METHODS: Streptozotocin (STZ)
      induced diabetic neuropathy in rats was monitored by measuring blood sugar
      levels, motor nerve conduction velocity (MNCV), nociception and histopathology of
      tibial nerve. Forty rats were divided in to four groups of 10 each. Group I:
      Control (vehicle). Group II: STZ (50mg/kg, iv, single injection). Group III:
      Lacidipine (0.5 mg/kg, po, daily + STZ). Group IV: STZ + insulin (4 unit/kg, sc,
      bid). Similar protocol was used for other parameters also. RESULTS: Lacidipine
      pre-treatment failed to reduce blood sugar levels in diabetic rats but prevented
      deterioration of motor nerve conduction velocity as compared to STZ diabetic
      rats. Hyperalgesia induced by STZ was antagonized by lacidipine. Histology of
      nerve showed less structural damage in lacidipine pre-treated group. DISCUSSION
      AND CONCLUSION: Thus, lacidipine prevents the development of neuropathic changes
      induced by STZ in rats.

PMID- 21091186
TI  - Infection reduction strategies including antibiotic stewardship protocols in
      surgical and trauma intensive care units are associated with reduced resistant
      gram-negative healthcare-associated infections.
AB  - BACKGROUND: Resistance to broad-spectrum antibiotics by gram-negative organisms
      is increasing. Resistance demands more resource utilization and is associated
      with patient morbidity and death. We describe the implementation of infection
      reduction protocols, including antibiotic stewardship, and assess their impact on
      multi-drug-resistant (MDR) healthcare-acquired gram-negative infections. METHODS:
      Combined infection reduction and antibiotic stewardship protocols were
      implemented in the surgical and trauma intensive care units at Vanderbilt
      University Hospital beginning in 2002. The components of the program were: (1)
      Protocol-specific empiric and therapeutic antibiotics for healthcare-acquired
      infections; (2) surgical antibiotic prophylaxis protocols; and (3) quarterly
      rotation/limitation of dual antibiotic classes. Continuous healthcare-acquired
      infection surveillance was conducted by independent practitioners using National
      Heath Safety Network criteria. Linear regression analysis was used to estimate
      trends in MDR gram-negative healthcare-acquired infections. RESULTS: A total of
      1,794 gram-negative pathogens were isolated from healthcare-acquired infections
      during the eight-year observation period. The proportion of healthcare-acquired
      infections caused by MDR gram-negative pathogens decreased from 37.4% (2001) to
      8.5% (2008), whereas the proportion of healthcare-acquired infections caused by
      pan-sensitive pathogens increased from 34.1% to 53.2%. The rate of total
      healthcare-associated infections per 1,000 patient-days that were caused by MDR
      gram-negative pathogens declined by -0.78 per year (95% confidence interval [CI] 
      1.28, -0.27). The observed rate of healthcare-acquired infections per 1,000
      patient days attributable to specific MDR gram-negative pathogens decreased over
      time: Pseudomonas -0.14 per year (95% CI -0.20, -0.08), Acinetobacter-0.49 per
      year (95% CI -0.77, -0.22), and Enterobacteriaceae -0.14 per year (95% CI -0.26, 
      0.03). CONCLUSION: Implementation of an antibiotic stewardship protocol as a
      component of an infection reduction campaign was associated with a decrease in
      resistant gram-negative healthcare-acquired infections in intensive care units.
      These results further support widespread implementation of such initiatives.

PMID- 21091187
TI  - Effects of metabolic syndrome on cardio-ankle vascular index in middle-aged and
      elderly Chinese.
AB  - Metabolic syndrome is characterized by multiple risk factors and is associated
      with increased risk of diabetes and cardiovascular disease. The rapid change in
      the lifestyle and food habits of Chinese people has resulted in metabolic
      syndrome becoming one of the most widespread health challenges in China.
      Recently, the cardio-ankle vascular index (CAVI) was developed as a new parameter
      reflecting arterial stiffness and providing an index of vascular status. The
      purpose of this study was to investigate the effect of metabolic syndrome on
      CAVI. A total of 222 Chinese subjects aged 50-92 years participated in this
      study. We measured CAVI and examined blood samples to define metabolic syndrome
      according to the International Diabetes Federation criteria. CAVI in the subjects
      with abnormal waist circumference was significantly higher than that obtained in
      the normal subjects (P < 0.01). In the abnormal high-density lipoprotein
      cholesterol (HDL-C) group, CAVI was significantly increased (P < 0.01) compared
      to the normal HDL-C group. CAVI showed a positive correlation with waist
      circumference and increased significantly with the number of metabolic syndrome
      components. In conclusion, subjects with metabolic syndrome have a high CAVI that
      indicated arterial stiffness and is closely associated with an increase in the
      number of metabolic syndrome risk factors. Elevated abdominal obesity and low HDL
      C are the main players affecting arterial stiffness in the middle-aged and
      elderly Chinese. These findings suggest that interaction of the individual
      components of metabolic syndrome plays a role in the relationship between
      metabolic syndrome and arterial stiffness.

PMID- 21091188
TI  - A challenging case of bilateral iliopsoas abscess.
AB  - BACKGROUND: Bilateral iliopsoas abscess is very rare and has never been reported
      in cases of aortic graft infections. To date, only cases of unilateral abscess
      have been reported in association with aortic graft infection, and even these are
      uncommon. METHODS: Case report and literature review. RESULTS: We present the
      first report of an infected abdominal aortic graft, secondary to an ileal
      perforation, in a 76-year-old woman presenting with bilateral iliopsoas abscess.
      The presence of lumbar spondylodiscitis initially led us to suspect this as the
      primary cause of the abscess. Hence, she was treated initially with drainage of
      the abscess, percutaneously and surgically. This proved to be unsuccessful. A
      laparotomy, excision of the aortic graft, and in situ revascularization with a
      femoral venous conduit was performed subsequently. The bilateral iliopsoas
      abscess was found to be caused by a perforation of the ileum. Despite the
      surgery, the patient finally succumbed. CONCLUSIONS: Bilateral iliopsoas abscess
      secondary to infected aortic graft is extremely rare and challenging. Drainage of
      the abscess, percutaneously or surgically, and excision of graft with or without
      revascularization must be considered carefully based on the individual case.

PMID- 21091189
TI  - Targeted blockage of signal transducer and activator of transcription 5 signaling
      pathway with decoy oligodeoxynucleotides suppresses leukemic K562 cell growth.
AB  - The protein signal transducer and activator of transcription 5 (STAT5) of the
      JAK/STAT pathway is constitutively activated because of its phosphorylation by
      tyrosine kinase activity of fusion protein BCR-ABL in chronic myelogenous
      leukemia (CML) cells. This study investigated the potential therapeutic effect of
      STAT5 decoy oligodeoxynucleotides (ODN) using leukemia K562 cells as a model. Our
      results showed that transfection of 21-mer-long STAT5 decoy ODN into K562 cells
      effectively inhibited cell proliferation and induced cell apoptosis. Further,
      STAT5 decoy ODN downregulated STAT5 targets bcl-xL, cyclinD1, and c-myc at both
      mRNA and protein levels in a sequence-specific manner. Collectively, these data
      demonstrate the therapeutic effect of blocking the STAT5 signal pathway by cis
      element decoy for cancer characterized by constitutive STAT5 activation. Thus,
      our study provides support for STAT5 as a potential target downstream of BCR-ABL
      for CML treatment and helps establish the concept of targeting STAT5 by decoy ODN
      as a novel therapy approach for imatinib-resistant CML.

PMID- 21091190
TI  - Resilience to loss and potential trauma.
AB  - Initial research on loss and potentially traumatic events (PTEs) has been
      dominated by either a psychopathological approach emphasizing individual
      dysfunction or an event approach emphasizing average differences between exposed
      and nonexposed groups. We consider the limitations of these approaches and review
      more recent research that has focused on the heterogeneity of outcomes following
      aversive events. Using both traditional analytic tools and sophisticated latent
      trajectory modeling, this research has identified a set of prototypical outcome
      patterns. Typically, the most common outcome following PTEs is a stable
      trajectory of healthy functioning or resilience. We review research showing that
      resilience is not the result of a few dominant factors, but rather that there are
      multiple independent predictors of resilient outcomes. Finally, we critically
      evaluate the question of whether resilience-building interventions can actually
      make people more resilient, and we close with suggestions for future research on
      resilience.

PMID- 21091192
TI  - Theoretical study of negative molecular ions.
AB  - Although this review provides references to tabulations of molecular electron
      affinities, primarily it focuses on explaining why theory plays an important role
      in understanding the behavior of anions, explaining the challenges that anions
      pose to theory, making connections between the theories used to compute electron
      affinities and the potentials (e.g., charge-dipole, charge-quadrupole, valence
      attraction and exchange repulsion, dispersion, and polarization) that govern the
      electron-molecule interaction, and discussing how species with negative electron
      affinities may possess metastable anion states and how such states should be
      treated. In addition to references to published literature, many links are given
      to websites of practicing theoretical chemists who study molecular anions; these
      links (which appear in boldface) offer the reader a broad avenue to access much
      more information about molecular anions than can be covered in a review or even
      through conventional literature sources.

PMID- 21091191
TI  - Efficacy of intravenous iron for treating postpartum anemia in low-resource
      African countries: a pilot study in Malawi.
AB  - BACKGROUND: Postpartum hemorrhage may lead to maternal morbidity and mortality,
      increases risks of transfusion, and incurs costs. We report on the feasibility
      and efficacy of in-hospital intravenous (IV) iron for treating postoperative
      anemia at Mtengo wa Nthenga, Malawi. PATIENTS AND METHODS: Twenty-eight
      consecutive women undergoing surgery for complicated pregnancy or complicated
      childbirth entered the study. Patients with hemoglobin (Hb) <10 g/dL on
      postoperative day 1 (n = 14) received IV iron sucrose (200 mg/day, 3 consecutive
      days), and those with Hb >=10 g/dL (n = 14) received oral iron (ferrous sulfate,
      256 mg/day). In-hospital postoperative Hb increase and blood transfusion were
      recorded. RESULTS: Mean changes in Hb from postoperative day 1 to postoperative
      day 7 were -0.6 +/- 1.2 g/dL and 2.1 +/- 1.7 g/dL, for the oral and IV iron
      groups, respectively (p = 0.001). No side effect was seen with IV iron. Only 1 of
      4 women receiving allogeneic blood was transfused after the initiation of IV iron
      treatment. CONCLUSIONS: Our results suggest that IV iron sucrose is an effective
      drug for treating puerperal anemia, leading to a rapid recovery of Hb levels. The
      current availability of generic iron sucrose preparations, with considerably
      lower acquisition costs, may facilitate in-hospital access to this treatment
      option in low-resource countries.

PMID- 21091193
TI  - Ionic liquids: structure and photochemical reactions.
AB  - Ionic liquids are subjects of intense current interest within the physical
      chemistry community. A great deal of progress has been made in just the past five
      years toward identifying the factors that cause these salts to have low melting
      points and other useful properties. Supramolecular structure and organization
      have emerged as important and complicated topics that may be key to understanding
      how chemical reactions and other processes are affected by ionic liquids. New
      questions are posed, and an active debate is ongoing regarding the nature of
      nanoscale ordering in ionic liquids. The topic of reactivity in ionic liquids is
      still relatively unexplored; however, the results that have been obtained
      indicate that distributed kinetics and dynamical heterogeneity may sometimes, but
      not always, be influencing factors.

PMID- 21091194
TI  - Climate change, noncommunicable diseases, and development: the relationships and
      common policy opportunities.
AB  - The rapid growth in noncommunicable diseases (NCDs), including injury and poor
      mental health, in low- and middle-income countries and the widening social
      gradients in NCDs within most countries worldwide pose major challenges to health
      and social systems and to development more generally. As Earth's surface
      temperature rises, a consequence of human-induced climate change, incidences of
      severe heat waves, droughts, storms, and floods will increase and become more
      severe. These changes will bring heightened risks to human survival and will
      likely exacerbate the incidence of some NCDs, including cardiovascular disease,
      some cancers, respiratory health, mental disorders, injuries, and malnutrition.
      These two great and urgent contemporary human challenges-to improve global
      health, especially the control of NCDs, and to protect people from the effects of
      climate change-would benefit from alignment of their policy agendas, offering
      synergistic opportunities to improve population and planetary health. Well
      designed climate change policy can reduce the incidence of major NCDs in local
      populations.

PMID- 21091195
TI  - The social determinants of health: coming of age.
AB  - In the United States, awareness is increasing that medical care alone cannot
      adequately improve health overall or reduce health disparities without also
      addressing where and how people live. A critical mass of relevant knowledge has
      accumulated, documenting associations, exploring pathways and biological
      mechanisms, and providing a previously unavailable scientific foundation for
      appreciating the role of social factors in health. We review current knowledge
      about health effects of social (including economic) factors, knowledge gaps, and
      research priorities, focusing on upstream social determinants-including economic
      resources, education, and racial discrimination-that fundamentally shape the
      downstream determinants, such as behaviors, targeted by most interventions.
      Research priorities include measuring social factors better, monitoring social
      factors and health relative to policies, examining health effects of social
      factors across lifetimes and generations, incrementally elucidating pathways
      through knowledge linkage, testing multidimensional interventions, and addressing
      political will as a key barrier to translating knowledge into action.

PMID- 21091196
TI  - Progression of symptoms and functioning among female cardiac patients with and
      without diabetes.
AB  - OBJECTIVE: To determine if older women with both heart disease and diabetes
      experience worse physical and psychosocial functioning and higher symptom burden
      over an 18-month period compared with those with heart disease alone. METHODS:
      Data from older women with heart disease (>=60 years, n = 1008, 18% with
      diabetes) were used to assess the impact of diabetes on physical functioning
      (Sickness Impact Profile [SIP]-Physical and Six-Minute Walk test [6MWT]),
      psychosocial functioning (SIP-Psychosocial and depressive symptoms), and physical
      symptom burden (cardiac and general) at baseline and 4, 12, and 18 months later.
      Generalized estimating equation models compared trends in outcomes over time
      between groups with and without diabetes. RESULTS: Across all four time points,
      women with heart disease and diabetes had greater functional impairment, as
      indicated by higher SIP scores, than those without diabetes (43%-71% higher SIP
      Physical scores and 32%-65% higher SIP-Pyschosocial scores; all p <= 0.002). 6MWT
      distance was 17%-30% less in the diabetes group across time points (all p <=
      0.002). Depressive symptoms were 27%-39% higher in the diabetes group (all p <
      0.03) except at month 4. Women with diabetes scored 15%-29% higher on a physical
      symptom index across time points (all p < 0.05) than those without diabetes; no
      significant differences were observed in cardiac symptoms until month 18
      (diabetes group 29% higher, p = 0.02). Subgroups with and without diabetes in
      this sample experienced significantly different trends over time in SIP-Physical
      scores (p = 0.02) and 6MWT distance (p = 0.05), such that the disadvantage of the
      diabetes group at baseline was greater 18 months later. CONCLUSIONS: Women with
      comorbid diabetes and heart disease are vulnerable to poor health-related quality
      of life, particularly in terms of physical functioning and symptoms, and require
      special efforts from clinical care providers to ameliorate a potential downward
      trend in these outcomes over time.

PMID- 21091197
TI  - Risk factors for cervical abnormalities among Hong Kong Chinese women: a large
      scale community-based cervical screening program.
AB  - BACKGROUND: We sought to identify the prevalence of and risk factors associated
      with cervical abnormalities among Chinese women in Hong Kong. METHODS: A
      community-based cervical screening program was offered free of charge in Hong
      Kong. Information on the demographics, sexual experience, and obstetrical history
      of women who attended the Cervical Screening Clinic were collected and tabulated
      with their Pap smear results to establish the risk factors associated with
      cervical abnormalities among Hong Kong Chinese women. RESULTS: A total of 44,219
      women attended the Cervical Screening Clinic for their first Pap smear tests over
      an 8-year period, with the prevalence of cervical abnormality at 4.51%. Adjusted
      for all associating factors, the significant risk factors of cervical
      abnormalities identified among Hong Kong Chinese women are being aged 40-49 (odds
      ratio [OR] 1.53), being single (OR 1.52) or cohabiting (OR 1.52), having received
      primary school education only (OR 1.53), having had three or more sexual partners
      (OR 1.52), onset of sexual activity at age <=18 (OR 1.53), having reported
      bleeding after intercourse (OR 1.44), and having had more than three pregnancies
      (OR 1.47). Condom use was identified as the single most significant protective
      factor reducing the risk of cervical abnormalities among these women (OR 0.76).
      CONCLUSIONS: This first population study in Hong Kong provides a better
      understanding of the risk factors associated with cervical abnormalities among
      Hong Kong Chinese women. A primary preventive strategy to reduce cervical cancer
      incidence should focus on modifying these preventable risk factors, complemented
      by population-based cervical screening programs to increase the coverage rate to
      80% in the long term, together with human papillomavirus (HPV) vaccination.

PMID- 21091198
TI  - Climate change and elevated extinction rates of reptiles from Mediterranean
      Islands.
AB  - Recent climate change has caused the distributions of many species to shift
      poleward, yet few empirical studies have addressed which species will be
      vulnerable to longer-term climate changes. To investigate past consequences of
      climate change, we calculated the population extinction rates of 35 reptile
      species from 87 Greek land-bridge islands in the Mediterranean that occurred over
      the past 16,000 years. Population extinction rates were higher for those species
      that today have more northern distributions. We further found that northern
      species requiring cool, mesic habitats had less available suitable habitat among
      islands, implicating loss of suitable habitat in their elevated extinction rates.
      These extinctions occurred in the context of increasing habitat fragmentation,
      with islands shrinking and separating as sea levels rose. Thus, the circumstances
      faced by reptiles on the islands are similar to challenges for numerous species
      today that must cope with a changing climate while living in an increasingly
      human-fragmented landscape. Our island-biogeographical approach to investigating
      historical population extinctions gives insight into the long-term patterns of
      species responses to climate change.

PMID- 21091199
TI  - Stirring up new ideas about the regulation of the hypothalamic-pituitary
      interrenal axis in zebrafish (Danio rerio).
AB  - The dynamic relationships between the changes in cortisol synthesis during and
      after a stressor and the expression pattern of the key genes that regulate the
      different levels of the hypothalamic-pituitary-interrenal (HPI) stress axis are
      poorly understood. This study established a novel vortex stressor and
      characterized its impact at all levels of the HPI axis in adult zebrafish.
      Exposure to a moderate vortex speed for 60 min was associated with a marked 18
      fold increase in whole-body cortisol after 10 min followed by a gradual return to
      basal values 30 min poststress. The changes in whole-body cortisol were
      paralleled by increases in the expression of preoptic area corticotropin
      releasing factor, pituitary prohormone convertase 1, and interrenal melanocortin
      2 receptor, steroid acute regulatory protein, 11beta-hydroxylase and 11beta
      hydroxysteroid dehydrogenase 2. The response to the vortex stressor also included
      delayed increases in preoptic area urotensin I and pituitary pro-opiomelanocortin
      mRNA levels but no change in the expression of other putative HPI axis
      regulators. Notably, the expression of several genes was depressed below control
      values 30 min poststress. These findings suggest that multiple genes at all
      levels of the HPI axis play an active role in the stimulation and termination of
      the cortisol stress response in zebrafish.

PMID- 21091200
TI  - Neonatal osteomyelitis and complex nephro-ureteral duplication.
AB  - OBJECTIVE: This report presents a case of femoral osteomyelitis secondary to
      urinary tract infection in a female neonate with bilateral urinary duplication
      and right ectopic ureterocele. METHODS: A female neonate with a history of late
      perinatal sepsis presented to the emergency department and was found to have left
      distal femoral osteomyelitis. A complex urological malformation was diagnosed
      (bilateral renal duplication with right ectopic ureterocele associated with
      nonfunctional superior pole of the ipsilateral kidney). The baby was submitted to
      prolonged antibiotic therapy and upper pole nephrectomy of the right kidney.
      RESULTS: The pathology report confirmed chronic pyelonephritis and dysplasia in
      the resected specimen. After 1.5 years the patient is asymptomatic and developing
      normally, with no apparent deformity, but manifests asymptomatic vesicoureteral
      reflux. CONCLUSIONS: Urinary tract infections must always be excluded as the
      primary infection focus in neonates with sepsis. Perinatal osteomyelitis is
      almost always a complication of neonatal sepsis and is associated with orthopedic
      sequelae. This is the first report in literature of a case of osteomyelitis
      complicating complex urinary duplication and urinary tract infection.

PMID- 21091201
TI  - Cloning and characterization of the 5'-flanking region of the pig cocaine- and
      amphetamine-regulated transcript gene.
AB  - The cocaine- and amphetamine-regulated transcript (CART) gene encodes an
      anorexigenic peptide. It has a key role in the hypothalamic regulation of energy
      balance through reducing food intake and enhancing lipid substrate utilization.
      To detect the CART expression pattern in pigs, reverse transcription (RT)
      polymerase chain reaction (PCR) and real-time PCR were performed in various
      tissues. Our RT-PCR results revealed that the pig CART gene was ubiquitously
      expressed in all examined tissues including hypothalamus, m. longissimus,
      backfat, heart, liver, spleen, lung, kidney, stomach, bladder, belly fat, brain,
      large intestine, lymph, and skin. Real-time quantitative PCR experiments revealed
      that the cDNA level of CART in both the hypothalamus and backfat of adult
      Landrace pig (lean-type) was significantly higher than that of Chinese indigenous
      Lantang pig (fat-type), and it was in the hypothalamus where the highest
      expression of CART was observed for both adult Lantang and Landrace pigs,
      compared with backfat and m. longissimus muscle. To understand the regulation of
      the pig CART gene, the 5'-flanking region was isolated from a pig bacterial
      artificial chromosome library and used in a luciferase reporter assay. A positive
      cis-acting element for efficient CART expression was identified at nucleotides 
      73 to -53, using 5'-serial deletion of the promoter. Electrophoretic mobility
      shift assays with competing oligonucleotides revealed that the critical region
      contained a cis-acting element for the zinc-binding protein factor, a zinc-finger
      transcription factor of the Kruppel family. This element has not been reported in
      human or mouse CART genes. Our results indicated that zinc-binding protein factor
      might be an essential regulatory factor for transcription of pig CART, providing
      important insight into mechanisms involved in energy homeostasis regulation in
      the porcine and human brain.

PMID- 21091202
TI  - Shorter axial length and increased astigmatic refractive error are associated
      With socio-economic deprivation in an adult UK cohort.
AB  - PURPOSE: To evaluate whether socio-economic deprivation is associated with ocular
      axial length and refractive error in a British cohort. METHODS: The study
      population consisted of 7,652 individuals who provided data to the prospective
      cataract database at Portsmouth Eye unit, UK over a 4 year period (January 2004
      to June 2008). Indices of multiple deprivation (IMD) scores measuring both social
      and economic domains for each patient's locality were calculated. The association
      of these measures of deprivation with axial length and refractive error
      (astigmatic and spherical) were evaluated using regression analyses after
      adjusting for age and sex. RESULTS: Socio-economically deprived areas (higher IMD
      scores) were inversely associated with axial lengths and astigmatic refraction.
      After controlling for age and sex, an inverse linear association was observed
      between axial length and IMD scores (-0.24 mm in highest quintile compared to
      lowest; 95% confidence intervals: -0.33 to -0.15) and between astigmatic
      refraction and IMD scores (-0.12 dioptres in highest quintile compared to lowest;
      95% confidence intervals: -0.21 to -0.03). There was no association between
      spherical refraction and IMD scores. CONCLUSIONS: Axial length and astigmatic
      refraction were inversely associated with socio-economic deprivation in this
      population. Identification of the environmental exposures involved may identify
      reversible risk factors for impaired vision.

PMID- 21091203
TI  - Adverse outcomes in nursing home residents with increased episodes of observed
      bacteriuria.
AB  - We examined the association between an increase in episodes of observed
      bacteriuria and adverse clinical outcomes among nursing home residents without
      catheters. Although bacteriuria was not associated with hospitalization for
      urinary tract infection (UTI) or change in mental status, it was associated with
      use of antibiotics to treat UTI and with isolation of multidrug-resistant gram
      negative rods from urine specimens, which suggested a causal relationship.

PMID- 21091204
TI  - An outbreak of carbapenem-resistant Acinetobacter baumannii infection in a
      neonatal intensive care unit: investigation and control.
AB  - OBJECTIVE: To investigate the mode of transmission of and assess control measures
      for an outbreak of carbapenem-resistant (multidrug-resistant) Acinetobacter
      baumannii infection involving 6 premature infants. DESIGN: An outbreak
      investigation based on medical record review was performed for each neonate
      during the outbreak (from November 2008 through January 2009) in conjunction with
      an infection control investigation. SETTING: A 36-bed, level 3 neonatal intensive
      care unit in a university-affiliated teaching hospital in Detroit, Michigan.
      INTERVENTIONS: Specimens were obtained for surveillance cultures from all infants
      in the unit. In addition, geographic cohorting of affected infants and their
      nursing staff, contact isolation, re-emphasis of adherence to infection control
      practices, environmental cleaning, and use of educational modules were
      implemented to control the outbreak. RESULTS: Six infants (age, 10-197 days) with
      multidrug-resistant A. baumannii infection were identified. All 6 infants were
      premature (gestational age, 23-30 weeks) and had extremely low birth weights
      (birth weight, 1000 g or less). Conditions included conjunctivitis (2 infants),
      pneumonia (4 infants), and bacteremia (1 infant). One infant died of causes not
      attributed to infection with the organism; the remaining 5 infants were
      discharged home. All surveillance cultures of unaffected infants yielded negative
      results. CONCLUSIONS: The spread of multidrug-resistant A. baumannii infection
      was suspected to be due to staff members who spread the pathogen through close
      contact with infants. Clinical staff recognition of the importance of multidrug
      resistant A. baumannii recovery from neonatal intensive care unit patients,
      geographic cohorting of infected patients, enhanced infection control practices,
      and staff education resulted in control of the spread of the organism.

PMID- 21091205
TI  - An evaluation of articulatory working space area in vowel production of adults
      with Down syndrome.
AB  - Many adolescents and adults with Down syndrome have reduced speech
      intelligibility. Reasons for this reduction may relate to differences in anatomy
      and physiology, both of which are important for creating an intelligible speech
      signal. The purpose of this study was to document acoustic vowel space and
      articulatory working space for two adult speakers with Down syndrome who had
      reduced speech intelligibility (mean = 56% based on single words). Articulatory
      data for the tongue were collected using a real-time flesh-point tracking method
      (i.e. X-ray microbeam). Results show smaller F1?F2 acoustic vowel space area for
      both speakers with Down syndrome compared with the control speakers. Reduced
      articulatory working space area and slower movement speed were also found for
      three of the four tongue points analysed. Although generalizations are limited by
      the small number of participants, findings warrant further investigation of the
      underlying articulatory characteristics of speech production for individuals with
      Down syndrome.

PMID- 21091206
TI  - Analysis of VOT in Turkish speakers with aphasia.
AB  - Studies investigating voicing onset time (VOT) production by speakers with
      aphasia have shown that nonfluent aphasics show a deficit in the articulatory
      programming of speech sounds based on the range of VOT values produced by aphasic
      individuals. If the VOT value lies between the normal range of VOT for the voiced
      and voiceless categories, then it is a phonetic distortion, thus a
      phonetic/articulatory deficit. A number of studies in different languages
      (French, English, Thai, Taiwanese) have investigated VOT in aphasic subjects in
      which their VOT values have been compared to those of normal speakers. This study
      investigates the VOT productions of voiced and voiceless stops by Turkish
      speakers with aphasia. Six patients with different aetiologies but similar
      language characteristics participated in this study. The results suggest that
      although Turkish nonfluent aphasics exhibit unimodal distribution of VOT
      production, the VOT values and ranges show language-specific properties.

PMID- 21091207
TI  - A longitudinal acoustic study of the effects of the radial forearm free flap
      reconstruction on sibilants produced by tongue cancer patients.
AB  - Acoustic properties of 980 tokens of sibilants /s, z, f/ produced by 17 Canadian
      English-speaking female and male tongue cancer patients were studied. The
      patients had undergone tongue resection and tongue reconstruction with a radial
      forearm free flap (RFFF). The spectral moments (mean, skewness) and frication
      duration were analysed in connected speech samples produced before the tongue
      resection, and 1, 6 and 12 months after the surgery. The effects of radiation
      therapy (RT) and inclusion of the floor of the mouth (FOM) were also studied.
      Acoustic changes were observed only on alveolar sibilants /s, z/ such that speech
      was found to improve towards normal over the 1-year period. The reduction of
      acoustic distinction between /s, z/ and /f/ was short term. A history of RT and
      involvement of the FOM had no differing effects on outcomes compared with non-RT
      or non-FOM. Variability between individuals was found, accentuating the speaker
      specific abilities for adaptation, compensation and relearning after oral
      reconstruction.

PMID- 21091209
TI  - Association between Caspase-9 promoter region polymorphisms and discogenic low
      back pain.
AB  - Caspase-9 (CASP-9) is an initiator caspase protease for apoptosis, and plays an
      important role in the development and progression of lumbar disc disease (LDD).
      The expression and/or activity of CASP-9 are significantly enhanced in the
      degenerated disc. The polymorphism in the promoter region of CASP-9 enhances the
      transcriptional activity of this gene, thereby modulating the susceptibility to
      LDD. The current study investigated the relationship between the CASP-9 -1263A/G
      (rs4645978) and -712C/T (rs4645981) polymorphisms and discogenic low back pain
      (LBP). The CASP-9 -1263A/G and -712C/T genotypes in this study were defined by
      polymerase chain reaction in 154 patients with discogenic LBP and 216 controls
      that were frequency-matched by age, gender, and occupation. The results showed
      that the CASP-9 -1263 GG genotype, compared with the AA and AG genotypes [odds
      ratio (OR) = 1.997, 95% confidence interval (95% CI) = 1.216-3.279, p = 0.006] or
      the AA genotype (OR = 2.760, 95% CI = 1.464-5.203, p = 0.002), is associated with
      a significant increased risk of discogenic LBP, but the -712 TT or TT and CT
      genotypes do not contribute to discogenic LBP compared with the CC genotype (OR =
      0.547, 95% CI = 0.200-1.494, p = 0.234 and OR = 0.669, 95% CI = 0.439-1.021, p =
      0.062, respectively). These results indicated that the CASP-9 -1263A/G
      polymorphism is associated with a high risk of discogenic LBP.

PMID- 21091210
TI  - Let the right one in: a microeconomic approach to partner choice in mutualisms.
AB  - One of the main problems impeding the evolution of cooperation is partner choice.
      When information is asymmetric (the quality of a potential partner is known only
      to himself), it may seem that partner choice is not possible without signaling.
      Many mutualisms, however, exist without signaling, and the mechanisms by which
      hosts might select the right partners are unclear. Here we propose a general
      mechanism of partner choice, "screening," that is similar to the economic theory
      of mechanism design. Imposing the appropriate costs and rewards may induce the
      informed individuals to screen themselves according to their types and therefore
      allow a noninformed individual to establish associations with the correct
      partners in the absence of signaling. Several types of biological symbioses are
      good candidates for screening, including bobtail squid, ant-plants, gut
      microbiomes, and many animal and plant species that produce reactive oxygen
      species. We describe a series of diagnostic tests for screening. Screening games
      can apply to the cases where by-products, partner fidelity feedback, or host
      sanctions do not apply, therefore explaining the evolution of mutualism in
      systems where it is impossible for potential symbionts to signal their
      cooperativeness beforehand and where the host does not punish symbiont
      misbehavior.

PMID- 21091211
TI  - Keystone predation and plant species coexistence: the role of carnivore hunting
      mode.
AB  - Plant communities are shaped by bottom-up processes such as competition for
      nutrients and top-down processes such as herbivory. Although much theoretical
      work has studied how herbivores can mediate plant species coexistence, indirect
      effects caused by the carnivores that consume herbivores have been largely
      ignored. These carnivores can have significant indirect effects on plants by
      altering herbivore density (density-mediated effects) and behavior (trait
      mediated effects). Carnivores that differ in traits, particularly in their
      hunting mode, cause different indirect effects on plants and, ultimately,
      different plant community compositions. We analyze a food-web model to determine
      how plant coexistence is affected by herbivore-consuming carnivores, contrasting
      those causing only density-mediated effects with those causing trait-mediated
      effects as well. In the latter case, herbivores can adjust their consumption of a
      refuge plant species. We derive a general graphical model to study the interplay
      of density- and trait-mediated effects. We show that carnivores eliciting both
      effects can sustain plant species coexistence, given intermediate intensities of
      behavioral adjustments. Coexistence is more likely, and more stable, if the
      refuge plant is competitively dominant. These results extend our understanding of
      carnivore indirect effects in food webs and show that behavioral effects can have
      major consequences on plant community structure, stressing the need for
      theoretical approaches that incorporate dynamical traits.

PMID- 21091212
TI  - Single-nucleotide polymorphisms of NKX2.5 found in congenital heart disease
      patients of Mysore, South India.
AB  - Congenital heart disease (CHD) is a common congenital birth defect, affecting
      nearly 1% of all live births, and is the most common cause of infant death.
      NKX2.5 is an important transcription factor expressed during vertebrate heart
      development and involved in the regulation of septation during cardiac
      morphogenesis and in the maturation and maintenance of the atrioventricular node
      throughout life. There are many reports on association of single-nucleotide
      polymorphisms (SNPs) of NKX2.5 with CHD but none have been reported from Mysore,
      South India. With informed consent, 150 clinically diagnosed CHD patients and 70
      unrelated healthy controls in Mysore, South India, were recruited. In the first
      phase the DNAs of 50 CHD patients and 20 controls were subjected to polymerase
      chain reaction amplification of coding regions of NKX2.5 and further sequenced
      for SNP genotyping. Additionally, mass array analysis of SNPs was performed for
      100 CHD and 50 controls. Analysis revealed the occurrence of six SNPs in
      different types of CHDs. Two were synonymous SNPs, the most common c.239A>G
      (p.E21E) and newly identified c.896C>A (p.A240A), as well as three nonsynonymous
      SNPs, c.608A>G (p.E203G), c.646C>T (p.R216C), and c.852G>A (p.N226D). The sixth
      SNP 1212G>T in the 3'UTR was observed in 40% of the CHD cases. The SNPs c.646C>T
      and c.608A>G were shown to cause changes in their secondary structure.
      Ventricular septal defect was the more prominent CHD observed in our study
      population. The SNPs c.608A>G (p.E203G) and c.852G>A (p.N226D) were present only
      in CHD patients, indicating their association with CHDs.

PMID- 21091213
TI  - Single-setting laparoscopic treatment of complete bilateral ureteral duplication
      in adult women.
AB  - BACKGROUND: Complete bilateral ureteral duplication has a low incidence in adult
      age. It is an uncommon etiology of urinary incontinence (UI) in adult women. The
      aim of this study is to report a series of 12 laparoscopic upper-pole partial
      nephrectomies, to highlight the feasibility of a single-setting treatment for
      this rare condition. PURPOSE: To report our experience with single-setting
      bilateral laparoscopic upper-pole partial nephrectomy (SSBLUPPN) for the
      treatment of UI in adult women affected by a complete bilateral ureteral
      duplication and hypofunctional upper-pole renal moieties. MATERIALS AND METHODS:
      Between February 2002 and November 2009, 6 female patients underwent SSBLUPPN for
      complete bilateral ureteral duplication with poorly functioning upper-pole renal
      moieties. Mean patient age was 38. Every patient complained of a continuous UI or
      a history of recurrent urinary tract infections (UTIs). All the patients
      underwent a preoperative evaluation with an abdominal ultrasonography, magnetic
      resonance imaging of the urinary tract, and a renal scan with DTC99. The analysis
      endpoint was the technical feasibility of SSBLUPPN as assessed by the operative
      time, estimated blood loss, postoperative course, and 3-year functional outcomes.
      RESULTS: All the procedures were successfully performed with no conversion to
      open surgery with a mean operative time of 244 minutes. Mean estimated blood loss
      was 236 cc. No major intraoperative complications occurred in all the cases. All
      the patients showed no clinical signs of UTIs postoperatively. At a mean follow
      up of 36 months, we found no hydronephrosis and complete remission of UI and UTIs
      in 100% of cases. CONCLUSIONS: SSBLUPPN is feasible and associated with minimal
      morbidity, an excellent cosmetic result, and a short hospital stay. A single
      setting treatment of complete ureteral duplication is a technically demanding
      procedure, and it should be performed only in centers with large experience in
      laparoscopic renal surgery.

PMID- 21091214
TI  - Contemporary experience with laparoscopic radical nephrectomy.
AB  - INTRODUCTION: We present our single-center contemporary experience with
      laparoscopic radical nephrectomy (LRN). LRN is an established minimally invasive
      approach comparable to open radical nephrectomy for the treatment of renal
      cortical neoplasms. Technical advancements and surgical experience with LRN
      mandate a re-evaluation of contemporary outcomes. METHODS: Between June 2005 and
      July 2009, 74 patients underwent LRN for an enhancing renal mass. Six of these
      patients underwent a cytoreductive nephrectomy for metastatic renal cell
      carcinoma. Patient demographics, perioperative data, tumor characteristics,
      complication rates, and outcomes were retrospectively collected and analyzed from
      our prospectively established renal database. RESULTS: The mean follow-up for
      patients undergoing nephrectomy without metastasis was 17.4 months (1-52 months).
      The mean estimated blood loss was 93 mL (0-600 mL) and the overall complication
      rate was 5.9%. Two patients developed metastatic disease after surgery, both of
      whom had high-stage (pT3a) tumors. No death was caused by renal cell carcinoma.
      In the cytoreductive cohort, the mean estimated blood loss was 592 mL (200-1200
      mL). Four were high stage (pT3a/pT3b). The mean follow-up was 4.7 months (1-15
      months), with an overall survival of 50%. CONCLUSIONS: With contemporary
      technology and increased laparoscopic surgical experience, LRN and, in selected
      cases, cytoreductive LRN can be performed safely and effectively for the majority
      of renal tumors. Experience has resulted in a reduction in operative time and
      blood loss complication rates. LRN remains the approach of choice for the
      management of renal cortical neoplasms not amenable to nephron-sparing surgery.

PMID- 21091215
TI  - Comparison of amplified fragment length polymorphism and pulsed-field gel
      electrophoresis for subtyping of Vibrio cholerae serogroups O1 and O139.
AB  - Molecular typing of Vibrio cholerae strains is a powerful tool for the
      surveillance of cholera. Amplified fragment length polymorphism (AFLP) is
      considered to be a powerful subtyping technique to distinguish bacterial strains
      at the genetic level. Optimization and standardization of AFLP protocol is
      required to allow data comparisons across different laboratories in a
      surveillance network. Here, we performed AFLP using different restriction enzymes
      and primer pairs for subtyping of V. cholerae serogroups O1 and O139 and compared
      the optimized AFLP protocol with pulsed-field gel electrophoresis (PFGE) to
      evaluate the applicability of AFLP for conducting epidemiological surveillance of
      cholera. The discriminatory index (D-value) of PFGE for serogroup O1 strains was
      similar when digested with NotI and SfiI, whereas that for O139 strains was
      higher for NotI digestion than for SfiI. EcoRI-G/MseI-T was the restriction
      enzyme and primer combination with highest discriminatory index used in the AFLP
      analysis. Capillary electrophoresis-based AFLP showed higher discriminatory power
      than that of polyacrylamide gel electrophoresis-based AFLP. When the two methods
      were compared using 72 epidemiologically unrelated serogroup O1 El Tor isolates,
      AFLP had a lower D-value than PFGE with NotI and SfiI digestions, respectively.
      For 54 epidemiologically unrelated serogroup O139 isolates, NotI PFGE had the
      highest discriminatory power, and SfiI PFGE and AFLP yielded almost the same but
      lower discriminatory power. We conclude that NotI and SfiI are both suitable for
      the PFGE of V. cholerae serogroup O1, whereas NotI should be defined as the
      primary enzyme for serogroup O139. The applicability of AFLP in V. cholerae
      subtyping and outbreak investigations is limited.

PMID- 21091216
TI  - Prevalence of Coxiella burnetii in bulk milk samples from dairy bovine, ovine,
      caprine, and camel herds in Iran as determined by polymerase chain reaction.
AB  - Q fever is a widespread zoonosis caused by the obligate intracellular micro
      organism Coxiella burnetii. The objective of this study was to determine the
      prevalence rate of C. burnetii in bulk milk samples from dairy bovine, ovine,
      caprine, and camel herds in Isfahan province, Iran. In the present study, 567
      bulk milk samples from 186 dairy bovine, ovine, caprine, and camel herds were
      tested for C. burnetii using a nested polymerase chain reaction assay. The
      animals whose milk samples collected for this study were clinically healthy. In
      total, 8 of 247 (3.2%) bovine milk samples were positive; the positive samples
      originated from 6 of 90 (6.7%) dairy herds. Eight of 140 (5.7%) ovine bulk milk
      samples from 42 sheep breeding farms and 5 of 110 (4.5%) caprine bulk milk
      samples from 32 goat breeding farms were positive for C. burnetii. One of 70
      (1.4%) camel bulk milk samples from 22 camel breeding farms was also positive for
      C. burnetii. Although no extensive prevalence study was undertaken, the results
      of this study indicate that clinically healthy dairy animals are important
      sources of C. burnetii infection in Iran. To the authors' knowledge, this study
      is the first report of direct identification of C. burnetii using polymerase
      chain reaction in bulk milk samples from dairy ovine herds in Iran and the first
      report of direct identification of C. burnetii in bulk milk samples from dairy
      camel herds. Further intensive prevalence studies on Coxiella infection and on
      possible risks of dairy products will be needed to elucidate the epidemiology of
      Q fever in Iran.

PMID- 21091217
TI  - DNA binding and gel electrophoresis studies of a new silver(I) complex containing
      2,9-dimethyl-1,10-phenanthroline ligands.
AB  - The silver(I) complex, [Ag(2,9-dimethyl-1,10-phenanthroline)(2)](NO(3)) . H(2)O,
      has been synthesized and characterized by physicochemical and spectroscopic
      methods. The binding interactions of this complex with calf thymus DNA (CT-DNA)
      were investigated using emission, absorption, circular dichroism, viscosity
      measurements, and gel electrophoresis studies. The calculated binding constant,
      K(b), obtained from UV-vis absorption studies was 5.3 +/- 0.2 * 10(4) M(-1). In
      fluorimetric studies, the enthalpy and entropy of the reaction between the
      complex and CT-DNA showed hydrophobic interaction. In addition, in the circular
      dichroism spectrum, silver(I) complex induces a B -> A structural transition of
      CT-DNA. Gel electrophoresis studies demonstrated that this complex has ability to
      cleave the supercoiled plasmid DNA. All these results suggest that the complex
      interacts with CT-DNA via partial intercalative mode of binding.

PMID- 21091218
TI  - The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary
      syndrome in a Chinese case-control study.
AB  - Numerous reports in the past few years have demonstrated that atherosclerosis is
      a lipid-driven, chronic inflammatory disease of the vessel. Recent studies have
      indicated that the immune mediator CD40-CD40L (CD40 ligand), which is expressed
      on several inflammatory cells within human atherosclerotic lesions, has roles in
      atherogenesis. A functional polymorphism (-1C>T, rs1883832) in the 5'
      untranslated region of TNFRSF5 gene has been reported to affect CD40 expression
      and be associated with several chronic inflammatory and autoimmune diseases. The
      aim of the present study was to validate the potential coronary artery disease
      susceptibility marker in a Chinese case-control study. A total of 160 patients
      with acute coronary syndrome (ACS) and 180 control subjects were used to genotype
      and identify this single-nucleotide polymorphism by polymerase chain reaction
      restriction fragment length polymorphism and sequencing, respectively. Peripheral
      blood mononuclear cells were isolated and incubated with interferon-gamma with or
      without pretreatment of fluvastatin, followed by measurement of CD40 expression
      using flow cytometry. In addition, soluble CD40L was determined by ELISA as
      another biomarker of coronary artery disease. The distribution of the rs1883832
      genotypes (CC, CT, and TT) was 33.1%, 54.4%, and 12.5% in the ACS group and
      22.8%, 53.3%, and 23.9% in controls, respectively. The frequency of the C allele
      was significantly higher among ACS patients compared with controls (60.3% vs.
      49.4%, odds ratio=1.554, 95% confidence intervals: 1.146-2.107, p<0.05). ACS
      patients showed a significant increase of CD40 and sCD40L coexpression compared
      with controls (p<0.05). Cell culture experiments showed that CC carriers
      presented significantly higher CD40 expression levels than CT and TT subjects
      (p<0.05). Additionally, fluvastatin suppressed CD40 expression in all three
      genotypes. These data suggest that the single-nucleotide polymorphism of CD40
      gene is associated with susceptibility to ACS in Chinese population, and the
      polymorphism may influence the CD40 production. These expand the understanding of
      inflammatory mechanisms during atherogenesis.

PMID- 21091219
TI  - Early developmental expression of Mus musculus zinc finger RNA-binding protein
      compared to orthologs in Caenorhabditis elegans and Danio rerio and subcellular
      localization of Mus musculus and Caenorhabditis elegans zinc finger RNA-binding
      protein in 2-cell Mus musculus embryos.
AB  - In mouse, knock-out of the Zfr gene encoding the zinc finger RNA-binding protein
      (ZFR) is associated with early lethality during gastrulation, suggesting that a
      pool of maternally contributed Zfr mRNA might compensate to allow development.
      ZFR is an ancient and highly conserved chromosome-associated protein from
      nematodes to mammals. We characterized expression of the Zfr transcript during
      early development in Mus musculus, Danio rerio, and Caenorhabditis elegans by
      quantitative real-time polymerase chain reaction. Mouse Zfr mRNA was detected in
      all stages tested during mouse preimplantation, with higher levels at the 1-cell
      stage that includes the maternal contribution of Zfr mRNA. In D. rerio, Zfr mRNA
      expression was highest in unfertilized eggs and declines throughout development.
      In C. elegans, Zfr mRNA expression was barely detectable in the fertilized egg
      and the L1 stage, but increased in the adult organism. Microinjections of green
      fluorescent protein (GFP)-tagged versions of in vitro-transcribed mouse and C.
      elegans Zfr mRNAs into early mouse embryos allowed analysis of the intracellular
      localization of the protein. Mouse ZFR-GFP was localized in the nucleus in 2-cell
      stage embryos although absent from nucleoli. Deletion studies revealed that this
      nuclear localization required the C-terminal part of ZFR, as deletion of the C
      terminal resulted in the localization to the nuclear membrane. Despite the lack
      of a conserved nuclear localization signal, the C. elegans ZFR-GFP fusion protein
      also displayed an intranuclear localization in the 2-cell mouse embryo.

PMID- 21091221
TI  - Carbon dioxide-based nephroscopy during laparoscopic pyeloplasty provides
      suboptimal view when stones are located in the lower calices.
AB  - Flexible nephroscopy while using carbon dioxide to insufflate the collecting
      system has been described as a "good trick" to remove caliceal stones during
      laparoscopic pyelolithotomy. We found this true only for those calices with
      undisturbed urine drain into the renal pelvis, while it provided suboptimal view
      of stones that were located in dependent lower pole calices. We describe how we
      dealt successfully with a group of lower pole caliceal stones during laparoscopic
      pyeloplasty.

PMID- 21091220
TI  - Comparison of the antihypertensive efficacy of irbesartan/HCTZ and valsartan/HCTZ
      combination therapy: impact of age and gender.
AB  - This analysis aimed to explore whether low-dose irbesartan/hydrochlorothiazide
      (HCTZ) has superior blood pressure (BP)-lowering efficacy over low-dose
      valsartan/HCTZ in the elderly and across both genders. This is a post-hoc
      analysis of data from a multicenter, parallel group, open-label, blinded-endpoint
      study in patients with hypertension uncontrolled with HCTZ monotherapy. The
      reduction in systolic BP (SBP)/diastolic BP (DBP) and rate of BP control achieved
      following 8 weeks of treatment with irbesartan/HCTZ 150/12.5 mg or valsartan/HCTZ
      80/12.5 mg were analyzed for older (>=65 years) vs. younger (<65 years) patients
      and for men vs. women. Blood pressure measurements were by home BP monitoring
      (HBPM). In the age and gender subgroups, both treatments significantly decreased
      home SBP and DBP (p < 0.0001). The reduction in home SBP and DBP was numerically
      greater with irbesartan/HCTZ compared to valsartan/HCTZ for all subgroups: the
      difference in DBP was significant for all except the elderly (p < 0.05), and the
      difference in SBP was significant in the elderly and in men (p < 0.03). In all
      subgroups, more patients achieved BP control (HBPM <=135/85 mmHg) in the
      irbesartan/HCTZ arm (range 45%-58%) than in the valsartan/HCTZ arm (range, 23%
      39%; p < 0.02). Both combination therapies were well tolerated and safety
      parameters were similar in both age and gender subgroups. More patients with mild
      or moderate hypertension, uncontrolled in HCTZ monotherapy alone, had their BP
      controlled with irbesartan/HCTZ 150/12.5 mg than with valsartan/HCTZ 80/12.5 mg,
      irrespective of age or gender.

PMID- 21091222
TI  - Hybrid laparoscopic endoscopic single-site surgery for radical cystoprostatectomy
      and orthotopic ileal neobladder: an initial experience of 12 cases.
AB  - BACKGROUND AND PURPOSE: Laparoscopic endoscopic single-site surgery (LESS) has
      recently emerged as an attempt to enhance cosmetic benefits and reduce morbidity;
      however, LESS for radical cystectomy is still not well established. Here we
      describe the technique of hybrid LESS for radical cystoprostatectomy and
      orthotopic ileal neobladder (RC-OIN), and evaluate its feasibility and safety.
      PATIENTS AND METHODS: Between November 2008 and October 2009, 12 men with bladder
      cancer underwent hybrid LESS for RC-OIN. A homemade multichannel port, made from
      two stretchable rings and a surgical glove with trocars and valves attached to
      its fingers, was placed into a 4- to 5-cm midline incision in the lower abdomen
      and was used for laparoscopic instruments. Another subumbilical port was placed
      for the laparoscope. Extended bilateral pelvic lymphadenectomy was performed by
      the lateral view; radical cystoprostatectomy was completed laparoscopically;
      construction of the ileal neobladder was performed extracorporeally; and the
      neobladder was anastomosed to the urethral stump laparoscopically, with a
      slipknot running suture technique. Perioperative, functional, oncologic data and
      complications were collected and analyzed. RESULTS: All operations were performed
      successfully without conversion to conventional laparoscopic radical cystectomy
      or open surgery. There was no perioperative mortality or port-related
      complications. The median operative time was 383 minutes. Median blood loss was
      150 mL. A median of 25 lymph nodes were removed. Surgical margins were tumor free
      in all cases. CONCLUSIONS: Hybrid LESS for RC-OIN is technically feasible with
      effects similar to those of conventional laparoscopic procedures. Further
      instrument and technique improvement are necessary to shorten operative time and
      reduce intraoperative difficulties.

PMID- 21091223
TI  - Histotripsy erosion of model urinary calculi.
AB  - BACKGROUND AND PURPOSE: Histotripsy is a pulsed focused ultrasound technology in
      which initiation and control of acoustic cavitation allow for precise mechanical
      fractionation of tissues. The present study examines the feasibility of using
      histotripsy for erosion of urinary calculi. MATERIALS AND METHODS: Histotripsy
      treatment was delivered from a 750-kHz transducer in the form of 5-cycle acoustic
      pulses at a 1-kHz pulse repetition frequency. Model stones were sonicated for 5
      minutes at peak negative pressures (p-) of 10, 15, 19, 22, and 24-MPa. Resulting
      fragment sizes and comminution rates were assessed and compared with those
      achieved with a piezoelectric lithotripter (Wolf Piezolith 3000) operated at 2-Hz
      pulse repetition frequency and power level 17 (p- = 14-MPa). RESULTS: Histotripsy
      eroded the surface of stones producing fine (< 100 MUm) particulate debris in
      contrast to the progressive and incomplete subdivision of stones achieved with
      piezoelectric lithotripsy. The histotripsy erosion rate increased with increasing
      peak negative pressure from 10 to 19 MPa and then saturated, yielding an average
      rate of 87.9 +/- 12.8 mg/min at maximum treatment intensity. Piezoelectric
      lithotripsy achieved an average treatment rate of 110.7 +/- 27.4 mg/min.
      CONCLUSIONS: Histotripsy comminution of urinary calculi is a surface erosion
      phenomenon that is mechanistically distinct from conventional shockwave
      lithotripsy (SWL), producing only fine debris as opposed to coarse fragments.
      These characteristics suggest that histotripsy offers a potential adjunct to
      traditional SWL procedures, and synergistic interplay of the two modalities may
      lead to possible increases in both rate and degree of stone fragmentation.

PMID- 21091224
TI  - Preservation of autonomic nerves in laparoscopic total radical hysterectomy.
AB  - OBJECTIVES: The aim of this study was to evaluate the feasibility, complications,
      margin status, and functional outcome (on urinary and sexual functions) of nerve
      sparing radical hysterectomy (NSRH) performed laparoscopically. METHODS: Patients
      with cervical carcinoma of stage Ia2 and Ib1 underwent laparoscopic NSRH along
      with pelvic lymphadenectomy. We performed the technique in simple comprehensible
      steps with anatomic delineation of the autonomic nerves and selective cutting of
      the uterine and cervical branches. RESULTS: Laparoscopic NSRH was feasible in
      85.7% of patients. Mean operative time was 160 minutes and all 7 patients had
      clear surgical margins. There were no complications and no blood transfusions
      were required. The median hospital stay was 3 days. The median return time for
      normal bladder function was 2 days and none of them required catheterization
      beyond 2 weeks. The mean residual urine volume was <50 mL. Urodynamic studies
      performed at 3 weeks after the operation showed no impairment of maximum flow
      rate (maximal flow rate: 20 +/- 2 mL). The postoperative results of sexual
      dysfunction were inconclusive. CONCLUSION: Understanding this technique and the
      knowledge of laparoscopic anatomy of pelvic autonomic nerves is important in both
      benign and malignant pelvic surgeries. These preliminary results indicate that
      nerve sparing is easier done laparoscopically and its results are comparable to
      that of conventional laparoscopic radical hysterectomy in terms of lateral margin
      status and lymph node yield. Whether quality of life can be benefited by L-NRSH
      technique and its long-term oncological sequelae need further evaluation.

PMID- 21091225
TI  - Exploring attitudes toward advance care directives in two diverse settings.
AB  - BACKGROUND: Advance care directives (ACD) are not used equally by different
      ethnic groups in the United States. Theories regarding this difference include
      lack of access to health care, mistrust of the health care system, absence of
      surrogate decision makers, and universal lack of knowledge on this topic. Few
      studies have investigated attitudes toward advance care planning for future end
      of-life decision-making in the Latino and Cambodian communities. METHODS: Six
      focus groups were conducted, including a total of 20 Latino and 19 Cambodian
      patients of two community health centers. Focus groups were audiotaped,
      transcribed, and qualitatively analyzed to identify major themes regarding
      attitudes toward advance directives and engaging in discussion about advance care
      planning. RESULTS: Most patients did not have a health care proxy nor had
      discussed this topic with their doctor. Two broad themes were identified:
      integration of belief systems (including religion, suffering/destiny, and
      importance of quality of life) as well as process/preferences regarding decision
      making (including family roles, provider roles, confusion/uncertainty regarding
      ACD, and openness to learning about ACD). CONCLUSIONS: In focus groups discussing
      end-of-life decision making among Latino and Cambodian patients, two main themes
      emerged: integration of belief systems and process/preferences regarding end-of
      life care. In particular, efforts to improve completion of advance care
      directives in diverse populations should consider patients' emphasis on quality
      of life and destiny in end-of-life planning as well as the role of family
      consensus in decision-making.

PMID- 21091226
TI  - Maternal support for human papillomavirus vaccination in Honduras.
AB  - BACKGROUND: Cervical cancer is a leading cause of cancer death for women in Latin
      America, and vaccinating against human papillomavirus (HPV) has the potential to
      limit this disease. We sought to determine Honduran women's awareness of HPV
      vaccination and interest in vaccinating their daughters against HPV. METHODS: We
      interviewed mothers aged >=17 at primary care clinics in Honduras. First, we
      collected demographic information and assessed knowledge related to cervical
      cancer prevention and awareness of HPV and HPV vaccination. Because most
      participants were not familiar with HPV, education about the relationships among
      HPV, sexual activity, and cervical cancer was provided before we asked
      participants if they would accept HPV vaccination for a 9-year-old daughter. We
      used multivariable logistic regression to determine predictors of vaccine
      acceptance. RESULTS: We interviewed 632 mothers. Only 13% had heard of HPV
      vaccination before the interview. After education, 91% would accept HPV
      vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew
      more at baseline about cervical cancer prevention than did those who did not
      endorse vaccination. Demographic characteristics did not predict vaccine
      acceptance. CONCLUSIONS: Few Honduran mothers were aware of HPV or HPV
      vaccination. However, most Honduran mothers would accept HPV vaccination for
      their daughters after receiving education about the relationship between HPV
      infection and cervical cancer. Baseline cervical cancer knowledge was associated
      with vaccine acceptance.

PMID- 21091227
TI  - Letter to the Editor: Is adult male circumcision a viable public health strategy
      for HIV prevention outside sub-Saharan Africa?

PMID- 21091228
TI  - Genetic variants in BCMO1 and CD36 are associated with plasma lutein
      concentrations and macular pigment optical density in humans.
AB  - Lutein is recovered at high concentration in the human macula lutea. Recent
      studies suggest that this micronutrient might be implicated in prevention of age
      related macular degeneration. OBJECTIVE: to identify genes which affect blood and
      retina lutein concentrations among candidate genes (intestinal sterol
      transporters and carotenoid oxygenases). DESIGN: a comparative plus an
      observational study. PARTICIPANTS: twenty-nine healthy subjects for the
      comparative study and 622 subjects for the observational study. INTERVENTION AND
      METHODS: all the participants were genotyped for single nucleotide polymorphisms
      (SNPs) in the candidate genes. Fasting plasma lutein concentrations were measured
      in all the participants and after 6 months' supplementation, with either a lutein
      rich supplement or a placebo, in the 29 subjects who participated in the
      comparative study. Macular pigment optical density (MPOD), which is a measure of
      macula concentration of lutein, was measured before and after the dietary
      intervention in the 29 subjects. Associations between SNPs and plasma lutein and
      MPOD were assessed by partial least square (PLS) regression followed by
      univariate analysis. Observed associations between SNPs and plasma lutein were
      verified by haplotype-based association analysis in the cohort of 622 subjects.
      MAIN OUTCOME MEASURES: plasma lutein levels and MPOD. RESULTS: six SNPs in four
      genes (ABCG8, BCMO1, CD36, and NPC1L1) explained 25% and 38% of the plasma and
      MPOD variance, respectively. Subjects with TT at the BCMO1 rs7501331 locus had
      lower (P < 0.05) plasma lutein than CT subjects. Subjects with CC at the CD36
      rs13230419 locus had lower (P < 0.05) plasma lutein than subjects who carried a T
      allele. The association between CD36 and plasma lutein was confirmed in the
      cohort of 622 subjects. Subjects with TT at the BCMO1 rs7501331 locus had a
      higher (P < 0.05) MPOD, and subjects with GG at rs1761667 CD36 locus had a higher
      (P < 0.05) MPOD than those with an A allele. CONCLUSIONS: these results suggest
      that BCMO1 and CD36 are implicated in plasma and retina concentrations of lutein
      and that genetic variants in these genes can modulate blood and retina
      concentrations of lutein.

PMID- 21091229
TI  - Hemoglobin A1c and glucose criteria identify different subjects as having type 2
      diabetes in middle-aged and older populations: the KORA S4/F4 Study.
AB  - OBJECTIVE: The American Diabetes Association (ADA) has recently recommended HbA1c
      for diagnosing diabetes as an alternative to glucose-based criteria. We compared
      the new HbA1c-based criteria for diagnosis of diabetes and prediabetes with the
      glucose-based criteria. RESEARCH DESIGN AND METHODS: In the population-based
      German KORA surveys (S4/F4) 1,764 non-diabetic participants aged 31-60 years and
      896 participants aged 61-75 years underwent measurements of HbA1c, fasting plasma
      glucose (FPG), and 2-h glucose. RESULTS: Only 20% of all subjects diagnosed with
      diabetes by glucose or HbA1c criteria had diabetes by both criteria; for
      prediabetes, the corresponding figure was 23%. Using HbA1c >= 6.5%, the
      prevalence of diabetes was strongly reduced compared to the glucose criteria
      (0.7% instead of 2.3% in the middle-aged, 2.9% instead of 7.9% in the older
      subjects). Only 32.0% (middle-aged) and 43.2% (older group) of isolated impaired
      glucose tolerance (i-IGT) cases were detected by the HbA1c criterion (5.7% <=
      HbA1c < 6.5%). CONCLUSION: By glucose and the new HbA1c diabetes criteria,
      different subjects are diagnosed with type 2 diabetes in middle-aged as well as
      older subjects. The new HbA1c criterion lacks sensitivity for impaired glucose
      tolerance.

PMID- 21091230
TI  - Letter to the Editor: Treatment as prevention: are HIV clinic patients interested
      in starting antiretroviral therapy to decrease HIV transmission?

PMID- 21091231
TI  - Evaluation of a rapid HIV testing initiative in an urban, hospital-based dental
      clinic.
AB  - Performing rapid HIV testing in nontraditional clinical settings such as dental
      clinics is a potential method for targeting high-risk individuals who may not
      otherwise access health care settings that offer HIV testing. In March 2008,
      Harlem Hospital Center, located in New York City, launched a counselor-based
      rapid HIV testing initiative in its on-site dental clinic. A full-time, trained
      counselor consented and tested patients as they waited for their appointments.
      HIV screening was performed using a whole-blood, finger-stick rapid HIV test.
      Through this initiative, 3864 HIV tests were performed from March 1, 2008 to
      December 31, 2009, representing 3565 unique individuals and 97.6% of dental
      patients approached for testing. Of those tested, the mean age was 38.5 years,
      with 47.1% female, 75.5% black, and 20.6% Hispanic. Self-reported HIV risk
      behaviors included 73.5% with recent unprotected heterosexual intercourse, 4.6%
      with recent or past injection drug use, and 2.6% who identified as men who have
      sex with men. Nineteen previously undiagnosed individuals (0.53%) were confirmed
      HIV positive. Of these individuals, mean age was 38.3 years with males
      representing 84.2%. Fifteen newly diagnosed patients (78.9%) were linked to care.
      Of those linked to care, median initial CD4 cell count was 317 cells/mm(3); 6 of
      these individuals (40%) had CD4 cell counts below 200 cells/mm(3). Our results
      demonstrate that a counselor-based rapid HIV testing program with linkage to
      specialized HIV care can be successfully integrated into the dental clinic
      setting.

PMID- 21091232
TI  - Predictors of nonadherence to highly active antiretroviral therapy among HIV
      infected South Indians in clinical care: implications for developing adherence
      interventions in resource-limited settings.
AB  - In light of the increasing availability of generic highly active antiretroviral
      therapy (HAART) in India, further data are needed to examine variables associated
      with HAART nonadherence among HIV-infected Indians in clinical care. We conducted
      a cross-sectional analysis of 198 HIV-infected South Indian men and women between
      January and April 2008 receiving first-line non-nucleoside reverse transcriptase
      inhibitor (NNRTI)-based HAART. Nonadherence was defined as taking less than 95%
      of HAART doses in the last 1 month, and was examined using multivariable logistic
      regression models. Half of the participants reported less than 95% adherence to
      HAART, and 50% had been on HAART for more than 24 months. The median CD4 cell
      count was 435 cells per microliter. An increased odds of nonadherence was found
      for participants with current CD4 cell counts greater than 500 cells per
      microliter (adjusted odds ratio [AOR]: 2.22 [95% confidence interval {CI}: 1.04
      4.75]; p = 0.038), who were on HAART for more than 24 months (AOR: 3.07 [95% CI:
      1.35-7.01]; p = 0.007), who reported alcohol use (AOR: 5.68 [95%CI: 2.10-15.32];
      p = 0.001), who had low general health perceptions (AOR: 3.58 [95%CI: 1.20
      10.66]; p = 0.021), and who had high distress (AOR: 3.32 [95%CI: 1.19-9.26]; p =
      0.022). This study documents several modifiable risk factors for nonadherence in
      a clinic population of HIV-infected Indians with substantial HAART experience.
      Further targeted culturally specific interventions are needed that address
      barriers to optimal adherence.

PMID- 21091233
TI  - Global trends in critical values practices and their harmonization.
AB  - BACKGROUND: The objectives of this article were 1) to identify current trends in
      critical values practices in North America, Europe, and other regions; 2) to
      describe progress toward harmonization of critical limits; and 3) to synthesize
      strategies that will encourage global consensus. Critical limits are described in
      national surveys. Critical value practices are guided by federal statutes, The
      Joint Commission regulations, and accreditation requirements in the US; by
      provincial healthcare agencies in Canada; by thought leaders and ISO EN
      15189:2007 in Europe; and in SE Asia, mostly by ad hoc policies lacking statutory
      grip. METHODS: Review of databases, literature, websites, federal statutes,
      litigation, official policies, current affairs, and accreditation agency
      requirements. RESULTS AND CONCLUSIONS: Practical strategies will accelerate
      harmonization of critical values practices, as follows: a) continue national and
      international survey comparisons; b) clarify age, ethnic, and subject
      dependencies; c) standardize qualitative and quantitative decision levels for
      urgent clinician notification; d) monitor compliance and timeliness for safety;
      and e) alert high frequencies of critical values related to adverse events. New
      expectations and communication technologies present opportunities for enhanced
      performance using wireless closed-loop reporting with recipient acknowledgment to
      reduce phone calls and improve efficiency. Hospitals worldwide can benefit from
      developing consensus for critical values practices.

PMID- 21091234
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) determined in urine with the
      Abbott Architect or in plasma with the Biosite Triage? The laboratory's point of
      view.

PMID- 21091235
TI  - Interaction between COX-2 G-765C and smoking in relation to coronary artery
      disease in a Chinese Uighur population.
AB  - BACKGROUND: Coronary artery disease (CAD) is a complex multifactorial and
      polygenic disorder where multiple environmental and genetic factors are involved
      simultaneously. The purpose of this study was to explore the relationship between
      the interaction of cyclooxygenase-2 (COX-2) gene polymorphism and smoking and CAD
      in a Uighur population. METHODS: Using a case-control study of Chinese Uighur CAD
      patients (n=430) and healthy controls (n=470), we investigated the roles of G
      765C polymorphism in the COX-2 gene (PTGS2) by the use of polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS:
      The PTGS2 GG genotype was significantly more prevalent in CAD patients (84.6% vs.
      78.3%; p=0.014). Multiple logistic regression analysis showed two independent
      risk factors: smoking (OR 1.89, 95% CI 1.01-5.24; p=0.008) and hypertension (OR
      2.73, 95% CI 1.59-7.21; p=0.001). Moreover, there was a synergistic effect
      between smoking and the PTGS2 polymorphism and the occurrence of CAD (interaction
      p=0.009). The odds ratio (OR) estimated by the combined analysis of the PTGS2 GG
      genotype and smoking history (OR 4.09, 95% CI 2.7-9.3) was markedly higher than
      that estimated separately from the PTGS2 GG genotype (OR 1.28, 95% CI 0.8-1.9) or
      smoking (OR 2.51, 95% CI 1.5-5.7) alone. Plasma 6-keto-PGF1alpha, a stable
      metabolite of PGI(2), was lower in individuals with the PTGS2 GG genotype
      (p<0.05). Smoking could further lower plasma 6-keto-PGF1alpha concentrations in
      GG genotype carriers than non-smokers, especially in patients with CAD.
      CONCLUSIONS: The PTGS2 polymorphism and smoking were synergistically and
      significantly associated in Chinese Uighur patients with CAD.

PMID- 21091236
TI  - Factor V Leiden and FII 20210 testing in thromboembolic disorders.
AB  - Factor V Leiden and prothrombin (F2) c.20210G>A mutation detection are very
      important in order to define the increased relative risk for venous
      thromboembolism in selected patients. Use of DNA-based methods to detect both
      mutations has become widely available in clinical diagnostic laboratories,
      including fluorescence-based quantitative real-time PCR (qPCR). The latter is a
      rapid, simple, robust and reliable method to identify genotypes of interest.
      There are several chemistries used for qPCR; this article describes their
      principles and applicability for Factor V Leiden and prothrombin (F2) c.20210G>A
      mutation detection.

PMID- 21091237
TI  - Condom use with steady partners among heterosexual people living with HIV in
      Europe: testing the information-motivation-behavioral skills model.
AB  - Guided by a modified information-motivation-behavioral skills model, this study
      identified predictors of condom use among heterosexual people living with HIV
      with their steady partners. Consecutive patients at 14 European HIV outpatient
      clinics received an anonymous, standardized, self-administered questionnaire
      between March and December 2007. Data were analyzed using descriptive statistics
      and two-step backward elimination regression analyses stratified by gender. The
      survey included 651 participants (n = 364, 56% women; n = 287, 44%). Mean age was
      39 years for women and 43 years for men. Most had acquired HIV sexually and more
      than half were in a serodiscordant relationship. Sixty-three percent (n = 229) of
      women and 59% of men (n = 169) reported at least one sexual encounter with a
      steady partner 6 months prior to the survey. Fifty-one percent (n = 116) of women
      and 59% of men (n = 99) used condoms consistently with that partner. In both
      genders, condom use was positively associated with subjective norm conducive to
      condom use, and self-efficacy to use condoms. Having a partner whose HIV status
      was positive or unknown reduced condom use. In men, higher education and
      knowledge about condom use additionally increased condom use, while the use of
      erectile-enhancing medication decreased it. For women, HIV disclosure to partners
      additionally reduced the likelihood of condom use. Positive attitudes to condom
      use and subjective norm increased self-efficacy in both genders, however, a
      number of gender-related differences appeared to influence self-efficacy. Service
      providers should pay attention to the identified predictors of condom use and
      adopt comprehensive and gender-related approaches for preventive interventions
      with people living with HIV.

PMID- 21091238
TI  - Applying the information-motivation-behavioral skills model in medication
      adherence among Thai youth living with HIV: a qualitative study.
AB  - With disproportionately higher rates of HIV/AIDS among youth and increasing
      access to antiretroviral therapy (ART) in Thailand, there is a growing urgency in
      understanding the challenges to medication adherence confronting this population
      and in developing theory-based interventions to address these challenges. One
      potentially relevant model, the information-motivation-behavioral skills (IMB)
      model of adherence, was developed in Western settings characterized by a more
      individualistic culture in contrast to the more collectivistic culture of
      Thailand. We explored the application and adaptability of IMB on ART adherence
      among HIV-positive Thai youth through the analysis of qualitative data from a
      pilot motivational interviewing study. Twenty-two interview sessions from 10 HIV
      positive Thai youth (17-24 years) were analyzed; 6 youth were on ART. Data
      support the utility of IMB as a potential framework for understanding ART
      adherence in this population. However, data indicate a consideration to expand
      the motivation construct of IMB to incorporate youths' perceived familial and
      social responsibilities and the need to adhere to medications for short- and long
      term well-being of self, family, and society in a context of Buddhist values.
      These modifications to IMB could be relevant in other cultural settings with more
      collectivistic worldviews.

PMID- 21091241
TI  - Tumor necrosis factor is critical for cytolytic T cell activity against
      allospecific hepatocytes and splenic targets in major histocompatibility complex
      class I disparate graft versus host disease.
AB  - The present studies determined the role of tumor necrosis factor (TNF)/tumor
      necrosis factor receptor (TNFR) interactions on cytolytic (CTL) activity of
      splenic and intrahepatic lymphocytes (IHL) isolated from mice undergoing graft
      versus host disease, induced by transfer of B6 T cells to major
      histocompatibility complex (MHC) class I disparate bm1 * B6 F1 mice. Allospecific
      killing of anti-H-2(bm1) splenic and hepatocyte targets was assessed by 4-h
      (51)Cr release and 16-h DNA lysis assays, respectively, utilizing spleen cells
      (SpC) and IHL isolated (1) from sublethally irradiated bm1 * B6 F1 who had
      received B6 spleen and bone marrow cells, and a control adenovirus (Adv-betagal)
      or a TNF inhibitor expressing adenovirus (Adv-TNFi), or (2) from bm1 * B6 F1
      recipients of B6, B6.129-Tnfrsf1a(tm1Mak)/J (TNFR1(-/-)), B6.129S2
      Tnfrsf1b(tm1Mwm)/J (TNFR2(-/-)), or B6.129S-Tnfrsf1a(tm1Imx) Tnfrsf1b(tm1Imx)/J
      (TNFR(-/-)) SpC and bone marrow cells, or (3) from in vitro-activated SpC.
      Splenic and IHL from bone marrow transplant recipients who had received Adv-TNFi
      at the time of transplant displayed lower allospecific CTL activity than
      controls. Addition of TNFR-Ig or a TNF antibody before the CTL activity assay
      further reduced allospecific killing against bm1 SpC blast targets. Both
      TNF/TNFR1 and TNF/TNFR2 interactions were critical for the development of optimal
      CTL activity against allospecific hepatocyte targets. Further, TNFR1- and TNFR2
      deficient SpC from MHC class I disparate mixed lymphocyte cultures displayed
      lower CTL activity and expression of effector molecules than control B6 SpC.
      TNF/TNFR interactions were critical for the development of optimal CTL activity
      of IHL and splenic cytotoxic T cells against MHC class I disparate SpC blast and
      hepatocyte targets in MHC class I disparate graft versus host disease.

PMID- 21091242
TI  - Association of vascular endothelial growth factor -2578C/A gene polymorphism in
      Chinese patients with colon cancer.
AB  - The vascular endothelial growth factor (VEGF) is an endothelial cell-specific
      mitogen involved in the process of angiogenesis, a crucial phase in tumor growth
      and metastasis. We carried out a case-control study to evaluate whether VEGF 
      2578C/A gene polymorphism modulates the risk of developing colon cancer. A total
      of 110 colon cancer patients and 110 cancer-free healthy people were recruited in
      the Chinese population. Genomic DNA was isolated from peripheral blood, and gene
      polymorphisms were analyzed by polymerase chain reaction-restriction fragment
      length polymorphism. Colon cancer patients had a significantly higher frequency
      of VEGF -2578AA genotype (odds ratio=2.49; 95% confidence interval=1.04, 6.01;
      p=0.04) than controls. Patients with left colon cancer had a significantly higher
      frequency of VEGF -2578AA genotype (odds ratio=2.31; 95% confidence
      interval=1.03, 5.18; p=0.04) than those with right colon cancer. When stratified
      by tumor size, growth pattern, differentiation, and stage of colon cancer, no
      statistically significant results were observed. This study suggested that VEGF 
      2578AA genotype was associated with a higher risk of colon cancer in Chinese
      population. Further studies are needed to understand the mechanism of VEGF gene
      polymorphisms in the development and progression of colon cancer.

PMID- 21091244
TI  - Effect of tetracalcium dimagnesium phytate on bone characteristics in
      ovariectomized rats.
AB  - The aim was to evaluate the influence of dietary Ca-Mg-phytate consumption on the
      bone characteristics of ovariectomized rats, an animal model for postmenopausal
      osteoporosis. Twenty ovariectomized female Wistar rats were randomly assigned to
      two groups fed, respectively, with a non-phytate diet (AIN-76A) or the same diet
      enriched with 1% phytate (as the calcium magnesium salt, phytin). After 12 weeks
      of feeding the rats were sacrificed, and both femoral bones and L4 vertebra were
      removed from each rat. Bone mass, length, width, volume, and mineral density were
      measured, and the phosphorus, calcium, magnesium, and zinc contents of bones were
      determined. Deoxypyridinoline (a bone resorption marker) was measured in urine,
      and osteocalcin (a bone formation marker) was measured in serum. The calcium and
      phosphorus contents and bone mineral density were significantly higher in both
      femoral bones and L4 vertebra for phytate-treated rats in comparison to rats in
      the non-phytate group. Deoxypyridinoline was significantly increased in rats in
      the non-phytate treatment group. Ca-Mg-phytate consumption reduces bone mineral
      density loss due to estrogen deficiency. Thus, phytate exhibits effects similar
      to those of bisphosphonates on bone resorption and may be of use in the primary
      prevention of osteoporosis if larger studies in humans confirm these findings.

PMID- 21091243
TI  - Effect of flash-heat treatment on antimicrobial activity of breastmilk.
AB  - BACKGROUND AND OBJECTIVES: The World Health Organization recommends human
      immunodeficiency virus (HIV)-positive mothers in resource-poor regions heat-treat
      expressed breastmilk during periods of increased maternal-to-child transmission
      risk. Flash-heat, a "low tech" pasteurization method, inactivates HIV, but
      effects on milk protein bioactivity are unknown. The objectives were to measure
      flash-heat's effect on antimicrobial properties of lactoferrin, lysozyme, and
      whole milk and on the digestive resistance of lactoferrin and lysozyme. METHODS:
      Flash-heated and unheated breastmilk aliquots from HIV-positive mothers in South
      Africa were "spiked" with Staphylococcus aureus and Escherichia coli and then
      cultured for 0, 3, and 6 hours. Lysozyme and lactoferrin activities were
      determined by lysis of Micrococcus luteus cells and inhibition of
      enteropathogenic E. coli, respectively, measured spectrophotometrically.
      Percentages of proteins surviving in vitro digestion, lactoferrin and lysozyme
      activity, and bacteriostatic activity of whole milk in heated versus unheated
      samples were compared. RESULTS: There was no difference in rate of growth of E.
      coli or S. aureus in flash-heated versus unheated whole milk (p = 0.61 and p =
      0.96, respectively). Mean (95% confidence interval) antibacterial activity of
      lactoferrin was diminished 11.1% (7.8%, 14.3%) and that of lysozyme by up to
      56.6% (47.1%, 64.5%) by flash-heat. Digestion of lysozyme was unaffected (p =
      0.12), but 25.4% less lactoferrin survived digestion (p < 0.0001). CONCLUSIONS:
      In summary, flash-heat resulted in minimally decreased lactoferrin and moderately
      decreased lysozyme bioactivity, but bacteriostatic activity of whole milk against
      representative bacteria was unaffected. This suggests flash-heated breastmilk
      likely has a similar profile of resistance to bacterial contamination as that of
      unheated milk. Clinical significance of the decreased bioactivity should be
      tested in clinical trials.

PMID- 21091245
TI  - Black soy peptide supplementation improves glucose control in subjects with
      prediabetes and newly diagnosed type 2 diabetes mellitus.
AB  - The present study aimed to determine the effect of black soy peptide
      supplementation on glucose control in subjects with prediabetes (impaired fasting
      glucose or impaired glucose tolerance) and newly diagnosed type 2 diabetes
      mellitus (DM). In this double-blind, placebo-controlled study, subjects with
      prediabetes and type 2 DM were randomly assigned to the placebo control group or
      the black soy peptide intervention group. We determined fasting serum
      concentrations of glucose, hemoglobin A1c, insulin, and free fatty acids,
      performed a 2-hour postload glucose (2-hour PG) test, and compared serum lipid
      profiles before and after the 12-week supplementation. In particular, subjects
      with fasting glucose >= 110 mg/dL who consumed black soy peptides tended to have
      lower fasting glucose levels (two-tailed test, P = .098; one-tailed test, P =
      .049) and had a significant reduction in 2-hour PG level (two-tailed P = .012,
      one-tailed P = .006), compared with baseline levels. The changes in 2-hour PG
      levels were also statistically significant in the intervention group (-41.25 +/-
      13.67 mg/dL) compared with the placebo group (12.42 +/- 9.80 mg/dL; two-tailed P
      = .015, one-tailed P = .008). In contrast, hemoglobin A1c levels were not
      significantly improved by the dietary intervention. In conclusion, black soy
      peptide supplementation may be beneficial for controlling fasting blood glucose
      levels and 2-hour PG levels.

PMID- 21091246
TI  - Adlay seed extract (Coix lachryma-jobi L.) decreased adipocyte differentiation
      and increased glucose uptake in 3T3-L1 cells.
AB  - The aim of the present study was to investigate effects of the ethyl acetate
      fraction of an ethanol extract of Coix lachryma-jobi (ECLJ) on glucose uptake and
      adipocyte differentiation in 3T3-L1 cells. ECLJ phosphorylated AMP-activated
      protein kinase (AMPK) and its downstream substrate acetyl-coenzymeA carboxylase
      in 3T3-L1 cells in a time- and dose-dependent manner. Moreover, we discovered
      that compound C inhibits ECLJ-stimulated ACC phosphorylation. In addition, ECLJ
      exhibited a dose-dependent stimulation of glucose uptake in 3T3-L1 cells, and
      this increase was obviously attenuated by compound C. ECLJ also caused a decrease
      in the expression levels of adipogenesis factors such as fatty acid synthase,
      sterol-regulatory-element-binding protein-1c, peroxisome proliferator-activated
      receptor gamma, and CAATT/enhancer binding protein alpha in a dose-dependent
      manner. Differentiation was examined by Oil red O staining activity after ECLJ
      treatment for 6 days. ECLJ decreased mean droplet size. These results suggest a
      possible role for AMPK in the process of adipose differentiation and that ECLJ
      targeted for adipocyte functions could be effective in improving the symptoms of
      metabolic syndrome.

PMID- 21091247
TI  - The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits
      monocyte binding to endothelial cells characteristic of early cardiovascular
      disease.
AB  - Regular consumption of fruits and vegetables is strongly associated with a
      reduced risk of cardiovascular disease (CVD). This effect occurs, in part,
      because of the plethora of bioactive agents in foods and their subsequent
      function as antioxidants. Ergothioneine (ERT), a novel antioxidant, is present in
      edible mushrooms and is not synthesized, but is accumulated, by humans through
      diet. In this study, we tested whether ERT, a bioactive agent, could interrupt
      pro-inflammatory induction of adhesion molecule expression associated with
      atherogenesis. Human aortic endothelial cells (HAECs) were incubated with
      increasing concentrations of ERT (0.01-10.0 mM) overnight (16 hours) followed by
      incubation with medium alone or with the pro-inflammatory cytokine interleukin
      (IL)-1beta (5 ng/mL) for 6 hours to induce expression of vascular cell adhesion
      molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial
      leukocyte adhesion molecule (ELAM-1 or E-selectin). ERT at 0.1-0.3 mM
      significantly (P < .05) reduced VCAM-1, ICAM-1, and E-selectin expression up to
      41%. VCAM-1 was suppressed to the greatest extent followed by E-selectin and then
      ICAM-1. We next tested if binding of preloaded U937 human monocytes to HAECs
      would be inhibited. U937 binding to HAECs was significantly reduced in IL-1beta
      stimulated HAECs preincubated with 1 and 3 mM ERT. Unstimulated monolayers
      demonstrated marginal, but significant, reductions. ERT was not toxic to HAECs at
      any concentration used. These data provide evidence that ERT found in commonly
      consumed dietary mushrooms can protect against events observed in atherogenesis,
      suggesting increased dietary intake of edible mushrooms would be a prudent
      medicinal means of reducing CVD risk.

PMID- 21091248
TI  - Ginger extract inhibits human telomerase reverse transcriptase and c-Myc
      expression in A549 lung cancer cells.
AB  - The rhizome of ginger (Zingiber officinale Roscoe) has been reputed to have many
      curative properties in traditional medicine, and recent publications have also
      shown that many agents in ginger possess anticancer properties. Here we show that
      the ethyl acetate fraction of ginger extract can inhibit the expression of the
      two prominent molecular targets of cancer, the human telomerase reverse
      transcriptase (hTERT) and c-Myc, in A549 lung cancer cells in a time- and
      concentration-dependent manner. The treated cells exhibited diminished telomerase
      activity because of reduced protein production rather than direct inhibition of
      telomerase. The reduction of hTERT expression coincided with the reduction of c
      Myc expression, which is one of the hTERT transcription factors; thus, the
      reduction in hTERT expression might be due in part to the decrease of c-Myc. As
      both telomerase inhibition and Myc inhibition are cancer-specific targets for
      cancer therapy, ginger extract might prove to be beneficial as a complementary
      agent in cancer prevention and maintenance therapy.

PMID- 21091249
TI  - The role of black rice (Oryza sativa L.) in the control of hypercholesterolemia
      in rats.
AB  - Cardiovascular disease is a serious public health problem; it is the first "cause
      of death" in Brazil and in developed countries. Thus, it is essential to search
      for alternative sources such as some functional foods to prevent and control the
      risks of this disease. The purpose of this study was to evaluate the lipidemic
      parameters in hypercholesterolemic rats fed diets containing black rice variety
      IAC 600 or unrefined rice. Adult male Wistar rats (Rattus norvegicus var.
      albinos) were used, weighing about 200-220 g. The animals were divided into four
      groups: the first received a control casein diet, the second received
      hypercholesterolemic diet, and the other two groups, after induction of
      hypercholesterolemia, received the test diets, the first containing 20% black
      rice and the second 20% unrefined, for 30 days. It was observed that diet
      containing black rice reduced the level of plasma cholesterol, triglycerides, and
      low-density lipoprotein. For high-density lipoprotein values, the diet that
      provided an increase in the levels was the black rice. The diet containing black
      rice was more effective in controlling the lipidemia in rats compared with the
      whole rice diet.

PMID- 21091250
TI  - Hemodynamic effects of lactotripeptides from casein hydrolysate in Mediterranean
      normotensive subjects and patients with high-normal blood pressure: a randomized,
      double-blind, crossover clinical trial.
AB  - Contrasting data partially support a certain antihypertensive efficacy of
      lactotripeptides derived from enzymatic treatment of casein hydrolysate. We
      carried out a randomized, double-blind, crossover clinical study to investigate
      the antihypertensive efficacy of a short-term treatment with lactotripeptides in
      Mediterranean subjects with normal or high-normal blood pressure (BP). We
      consecutively enrolled 55 untreated subjects (men:women = 30:25), 40.3 +/- 9.8
      years old, with normal or high-normal BP. After 4 weeks of dietary
      standardization, they were allocated to treatment with a fruit juice containing 3
      mg of added Ile-Pro-Pro/Val-Pro-Pro lactotripeptides or with placebo for 4 weeks.
      After a 4-week washout period, they were then assigned to the alternative
      treatment for a further period of 4 weeks. Overall, no significant difference has
      been observed in office BP comparing baseline data with those posttreatment.
      Repeating the analysis by basal BP level, a mild but significant reduction in
      systolic BP (-1.7 +/- 2.3 mm Hg; t = 3.5, P = .002) has been observed only in
      subjects with high-normal BP after treatment with lactotripeptides. With regard
      to 24-hour BP measurement, after lactotripeptide treatment only, the subjects
      experienced a significant reduction in diurnal diastolic BP (-1.6 +/- 5.4 mm Hg;
      P = .042), diurnal mean BP (-2.1 +/- 5.9 mm Hg; P = .19), and 24-hour (-5.4 +/-
      14.2 mm Hg; P = .011) and diurnal (-7.1 +/- 19.2%; P = .014) diastolic BP value
      measurements relative to normal values. No modification has been observed in
      relation to plasma renin activity and aldosteronemia. In conclusion, diurnal
      diastolic BP is significantly reduced by lactrotripeptide supplementation in
      untreated Mediterranean subjects with normal or high-normal BP. Office systolic
      BP is reduced only in subjects with high-normal BP.

PMID- 21091251
TI  - The herbal formula HT042 induces longitudinal bone growth in adolescent female
      rats.
AB  - The effect of HT042, a blend of three herbal extracts, on longitudinal bone
      growth was investigated in short- and long-term rat models. In the short-term
      model, we divided female Sprague-Dawley rats (3 weeks old) into six groups,
      according to treatment: vehicle, HT042 (100 mg/kg), Phlomis umbrosa (100 mg/kg),
      Astragalus membranaceus (100 mg/kg), and Eleutherococcus senticosus (100 mg/kg)
      were administered twice daily, and recombinant human growth hormone (rhGH) (1 IU)
      was subcutaneously injected once daily. Treatments were maintained for 4 days in
      each case. On day 3, tetracycline (20 mg/kg) was injected intraperitoneally (20
      mg/kg) to form the fluorescent band on the growth plates. On days 2-4, 5-bromo-2'
      deoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally to label
      proliferating cells. On day 5, the tibias were dissected and fixed in 30%
      sucrose. Dehydrated bone was sectioned at a thickness of 40 MUm and observed. The
      bone growth in groups administered HT042 and rhGH was significantly increased to
      433.50 +/- 21.61 and 434.49 +/- 15.21 MUm/day, respectively, from 410.03 +/- 17.4
      MUm/day (control). The height of the growth plates in the HT042 and rhGH groups
      was also significantly increased to 556.5 +/- 21.1 and 544.2 +/- 21.1 MUm (P <
      .05), respectively, from 518.1 +/- 4.1 MUm (normal). The number of BrdU-positive
      cells in chondrocytes of the HT042 and rhGH groups was increased to 389 +/- 36
      and 627 +/- 39 cells/mm2 (P < .001), respectively, from 264 +/- 17 cells/mm2
      (control). Insulin-like growth factor-1 and bone morphogenetic protein-2 in the
      HT042 group were highly expressed in the growth plate. In the long-term rat
      model, the body weight, nose-tail length, and nose-anus length were measured by
      microknemometry for 4 weeks. The body weight of the rhGH group was significantly
      increased. The nose-anus length of the HT042 and rhGH groups was significantly
      greater at 18.5 +/- 0.3 and 18.7 +/- 0.3 cm compared to 18.2 +/- 0.2 cm
      (control).

PMID- 21091252
TI  - Dietary polydextrose prevents inflammatory bowel disease in
      trinitrobenzenesulfonic acid model of rat colitis.
AB  - Inflammatory bowel disease (IBD) is a multifactorial intestinal disorder that
      involves interactions among the immune system, genetic susceptibility, and
      environmental factors, especially the bacterial flora. Polydextrose, a
      polysaccharide constituted by 90% nondigestible and nonabsorbable soluble fibers,
      has several physiological effects consistent with those of dietary fibers,
      including proliferation of colon microflora. Because sulfasalazine presents
      serious side effects through long-term use at high doses, the aim of the present
      study was to evaluate the preventative effect of polydextrose on
      trinitrobenzenesulfonic acid-induced intestinal inflammation and its effects on
      the intestinal anti-inflammatory activity of sulfasalazine. Results indicated
      that polydextrose and its association with sulfasalazine present an anti
      inflammatory effect that reduces myeloperoxidase activity, counteracts
      glutathione content, and promotes reductions in lesion extension and colonic
      weight/length ratio.

PMID- 21091253
TI  - Ginger (Zingiber officinale Roscoe) elicits antinociceptive properties and
      potentiates morphine-induced analgesia in the rat radiant heat tail-flick test.
AB  - Ginger (Zingiber officinale Roscoe), a well-known spice plant, has been used
      traditionally in the treatment of a wide variety of ailments. It has been shown
      that ginger is a calcium channel blocker; however, its influence on morphine
      analgesic effects has not been elucidated. We examined the effect of ginger root
      extract on nociceptive threshold and morphine-induced analgesia in male Wistar
      rats. To determine the effect of ginger on morphine analgesia, ginger extract
      (200, 400, and 600 mg/kg i.p.) was injected before a subeffective dose of
      morphine (2.5 mg/kg i.p.). The radiant heat tail-flick test was used to assess
      the nociceptive threshold before and at different times after drug
      administration. Our results showed that ginger extract elicited a significant
      antinociceptive effect. In addition, in groups that received both morphine and
      ginger, the observed analgesia was higher than that in groups treated with either
      morphine or ginger extract alone. Thus, the data indicate that ginger extract has
      a beneficial influence on morphine analgesia and can be an efficacious adjunct
      for pain management.

PMID- 21091254
TI  - Assessment of the genotoxic, antigenotoxic, and cytotoxic activities of the
      ethanolic fruit extract of Solanum lycocarpum A. St. Hill. (Solanaceae) by
      micronucleus test in mice.
AB  - Solanum lycocarpum A. St. Hill. (Family Solanaceae), popularly known in Brazil as
      lobeira, is a common weed in the Brazilian Cerrado vegetation. The fruits of this
      species have been used in Brazil for culinary purposes and in folk medicine as a
      sedative, diuretic, antiepileptic, antispasmodic, hypoglycemic, and
      hypocholesterolemic agent as well as in the control of obesity. Due to the
      spreading use of this plant as a therapeutic resource and food, the present study
      aimed to evaluate the genotoxic, antigenotoxic, and cytotoxic effects of S.
      lycocarpum ethanolic fruit extract using the mouse bone marrow micronucleus test.
      Both genotoxicity and antigenotoxicity of this ethanolic fruit extract were
      evaluated by using the frequency of micronucleated polychromatic erythrocytes,
      whereas cytotoxicity was assessed by the polychromatic and normochromatic
      erythrocytes ratio. Our results indicated that although S. lycocarpum ethanolic
      fruit extract did not exhibit genotoxic effect in mice bone marrow, both
      cytotoxic and antigenotoxic actions were evidenced at all tested doses.

PMID- 21091255
TI  - Heat processing decreases Amadori products and increases total phenolic content
      and antioxidant activity of Korean red ginseng.
AB  - The functional properties of Korean red ginseng (KRG) are known to be dependent
      upon the extent of heat processing. We demonstrated that repeated heat processing
      in the preparation of KRG decreased its arginyl-fructosyl-glucose (AFG) content
      and metal chelating capacity. On the other hand, the total phenolic compound
      content, in vitro peroxyl radical scavenging ability, and cellular peroxyl and
      hydroxyl radical scavenging ability increased with repeated heat processing. The
      peroxyl radical scavenging ability of KRG may be due to the total phenolic
      compound content. The hydroxyl radical scavenging ability of KRG seems to result
      mainly from the chelating ability of Amadori compounds such as arginyl-fructose
      and AFG. The protective ability of KRG against Cu2(+)-induced oxidative stress in
      hepatoma HepG2 cells may be due to permeability into the cell membrane rather
      than antioxidant activity. These results can be used to predict the physiological
      functions of KRG in in vivo models.

PMID- 21091256
TI  - Hemodialysis alters lipid profiles, total antioxidant capacity, and vitamins A,
      E, and C concentrations in humans.
AB  - Although hemodialysis (HD) is essential for end-stage renal disease patients, at
      the same time it causes oxidative stress and long-term pro-atherosclerotic
      effects. This study aimed to determine lipid profile as well as the total
      antioxidant capacity (TAC) and vitamins A, E, and C in HD patients. The study
      enrolled 31 patients (50.3 +/- 14.9 years old) undergoing maintenance 4-hour HD
      three times per week with a polysulfone membrane dialyzer for a mean of 76.1
      months (range, 7-120 months) and 31 healthy individuals (47.8 +/- 13.9 years
      old). Lipid profiles were determined spectrophotometrically using commercially
      available kits. Total antioxidant capacity was determined by ferric
      reducing/antioxidant power assay, levels of vitamins A and E were assayed using
      high-pressure liquid chromatography, and the level of vitamin C was measured by a
      photometric method. Our results showed that before HD, the levels of TAC and
      vitamin A were significantly higher than in normal subjects, whereas the levels
      of high-density lipoprotein (HDL) and vitamin C were lower than in control
      subjects (P < .001). There was no significant difference between normal subjects
      and patients before dialysis regarding low-density lipoprotein (LDL) and vitamin
      E levels (P > .05). After HD, the levels of HDL-cholesterol, vitamins E and C,
      and TAC decreased significantly (P < .001), but the decreased level of vitamin A
      still remained higher than controls (P < .05), whereas the levels of LDL were
      significantly higher than controls (P < .001). In conclusion, alterations in the
      lipoprotein profiles and antioxidant markers following HD suggest an increased
      risk of atherosclerosis in these patients.

PMID- 21091257
TI  - In vitro antioxidant and antimicrobial activities of two Hawaiian marine Limu:
      Ulva fasciata (Chlorophyta) and Gracilaria salicornia (Rhodophyta).
AB  - The antioxidant and antimicrobial properties of two Hawaiian marine algae (Ulva
      fasciata and Gracilaria salicornia) were evaluated. Ethanolic extracts of these
      two algae exhibited intracellular reactive 1,1-diphenyl-2-picrylhydrazyl, 2,2'
      azino-bis(3-ethylbenzthiazoline)-6-sulfonic radical, nitric oxide, superoxide
      radical, and hydroxyl radical scavenging activities. In addition to the
      antioxidant activity these algae possessed appreciable antimicrobial activity and
      total phenolic contents. The overall results have established that these two
      marine algae could be used to derive bioactive compounds for a possible role as
      nutraceutical agents.

PMID- 21091258
TI  - Essential oil of Thymus capitatus Hoff. et Link. from Matmata, Tunisia: gas
      chromatography-mass spectrometry analysis and antimicrobial and antioxidant
      activities.
AB  - Thymus capitatus Hoff. et Link. essential oil was constituted by thymol (89.06%)
      as a major component followed by p-cimene (5.04%) and gamma-terpinene (3.19%)
      after analysis by gas chromatography-flame ionization detection and gas
      chromatography-mass spectrometry. The antioxidant activity assays of the
      essential oil used in the inhibition of the radical cation 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonate) and the free radical 2,2-diphenyl-1
      picrylhydrazyl showed high 50% inhibitory concentration values of 1.24 +/- 0.05
      mg/L and 0.59 +/- 0.02 mg/L, respectively. The essential oil of T. capitatus was
      tested for antimicrobial activity against Gram-positive bacteria (Salmonella
      analum, Listeria monocytogenes), Gram-negative bacteria (Escherchia coli,
      Klebsiella pneumoniae), fungi (Mucor ramamnianus, Aspergillus ochraceus), and
      yeast species (Saccharomyces cerevisiae, Candida albicans) using the agar well
      diffusion method. It seemed that L. monocytogenes, E. coli, and K. pneumoniae
      bacteria were inhibited by the essential oil tested. A strong activity was also
      observed against fungi and yeasts.

PMID- 21091259
TI  - Mineral composition of different strains of edible medicinal mushroom Agaricus
      subrufescens Peck.
AB  - Agaricus subrufescens Peck is a well-known Basidiomycota fungus (Royal Sun
      Agaricus), with rising demand in consumption and production worldwide. This
      particular mushroom with high medical value has been used successfully in cancer
      therapy and in the treatment of some bacterial and viral diseases. Four strains
      of A. subrufescens (Si2.2, 853, 1105, and 2603) were cultivated, and 22 mineral
      elements of basidiomes (fruit bodies) were analyzed (caps and stipes separately).
      The data obtained about the mineral compositions were compared to the "reference"
      Agaricus bisporus (white button mushroom) and to the average of wild growing
      Agaricus species. The mineral composition of A. subrufescens strains can be
      characterized by the following: (1) high levels of valuable macroelements, i.e.,
      potassium (28-30,000 mg/kg of dry matter), phosphorus (7-11,000 mg/kg of dry
      matter), and calcium and magnesium (for both elements, 1,000-1,500 mg/kg of dry
      matter); (2) significantly higher level of copper (compared to A. bisporus, 70
      150 mg/kg of dry matter) and zinc (140-250 mg/kg of dry matter); (3) low quantity
      of sodium (140-180 mg/kg of dry matter); (4) attention should paid to the
      detectable amount of cadmium (2-17 mg/kg of dry matter) in strain Si2.2; (5) low
      or undetectable concentrations of some other poisonous microelements like As, Cr,
      and V; and (6) the distribution of elements in caps and stipes is characteristic
      the majority of beneficial elements have higher contents in caps than in stipes,
      but some other elements, such as Ca, Fe, and Na, appear in an inverse proportion.
      In conclusion, it can be said that the mineral composition of A. subrufescens is
      definitely positive, with the exception of the above-mentioned Cd level.

PMID- 21091260
TI  - Radical quenching activity, ferric-reducing antioxidant power, and ferrous ion
      chelating capacity of 16 Ballota species and their total phenol and flavonoid
      contents.
AB  - The ethyl acetate, methanol, and water extracts of 16 Ballota species (Family
      Lamiaceae)-Ballota acetabulosa, Ballota antalyanse, Ballota cristata, Ballota
      glandulosissima, Ballota inaequidens, Ballota larendana, Ballota latibracteolata,
      Ballota macrodonta, Ballota nigra ssp. anatolica, B. nigra ssp. foetida, B. nigra
      ssp. nigra, B. nigra ssp. uncinata, Ballota pseudodictamnus ssp. lycia, Ballota
      rotundifolia, Ballota saxatilis ssp. brachyodonta, and B. saxatilis subsp.
      saxatilis-were screened for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
      quenching, ferric-reducing antioxidant power, and ferrous ion-chelating capacity
      at 1mg/mL. Hispanolone, a major diterpene found in the Ballota genus, was also
      tested in the same manner. Total phenol and flavonoid contents of the extracts
      were determined by Folin-Ciocalteau and AlCl(3) reagents, respectively. The
      extracts showed insignificant quenching activity against DPPH radical, but they
      had moderate antioxidant activity (0.597 +/- 0.03 to 1.342 +/- 0.01) in the
      ferric-reducing test compared to chlorogenic acid (the reference compound) (3.618
      +/- 0.01). All of the extracts (ranging from 65.1 +/- 0.64% to 96.3 +/- 0.09%)
      and hispanolone (97.31 +/- 0.30%) exerted a remarkable ferrous ion-chelating
      effect. The highest total phenol (gallic acid equivalent) and flavonoid
      (quercetin equivalent) contents were found in the ethyl acetate extract of B.
      glandulosissima (393.7 +/- 3.03 and 140.6 +/- 1.97 mg/g of extract,
      respectively). Therefore, Ballota species could be a good source of natural
      preservatives in foodstuffs.

PMID- 21091261
TI  - Comparison of fluctuating maskers for speech recognition tests.
AB  - OBJECTIVE: To investigate the extent to which temporal gaps, temporal fine
      structure, and comprehensibility of the masker affect masking strength in speech
      recognition experiments. DESIGN: Seven different masker types with Dutch speech
      materials were evaluated. Amongst these maskers were the ICRA-5 fluctuating
      noise, the international speech test signal (ISTS), and competing talkers in
      Dutch and Swedish. STUDY SAMPLE: Normal-hearing and hearing-impaired subjects.
      RESULTS: The normal-hearing subjects benefited from both temporal gaps and
      temporal fine structure in the fluctuating maskers. When the competing talker was
      comprehensible, performance decreased. The ISTS masker appeared to cause a large
      informational masking component. The stationary maskers yielded the steepest
      slopes of the psychometric function, followed by the modulated noises, followed
      by the competing talkers. Although the hearing-impaired group was heterogeneous,
      their data showed similar tendencies, but sometimes to a lesser extent, depending
      on individuals' hearing impairment. CONCLUSIONS: If measurement time is of
      primary concern non-modulated maskers are advised. If it is useful to assess
      release of masking by the use of temporal gaps, a fluctuating noise is advised.
      If perception of temporal fine structure is being investigated, a foreign
      language competing talker is advised.

PMID- 21091262
TI  - Development of a Mandarin tone identification test: sensitivity index d' as a
      performance measure for individual tones.
AB  - OBJECTIVE: The aim of this study was to develop comprehensive test material for
      Mandarin tone identification in noise for a male and a female talker.
      Additionally, the sensitivity index d' as a measure for the listeners'
      performance to identify individual tones was evaluated. DESIGN: The study
      followed a prospective design. STUDY SAMPLE: The complete material comprises 72
      loudness-balanced syllables in all 4 Mandarin tones. For a selection of 20
      syllables, i.e. 80 test words, performance-versus-intensity functions were
      measured in spectrally matched noise for 16 normal-hearing participants. RESULTS:
      The average speech reception thresholds in noise were -12.9 dB for the male and 
      13.6 dB for the female talker recordings. The corresponding slopes were 8.6%/dB
      and 7.3%/dB. As a performance measure for individual tones, the proportion of
      correct responses to specific tones was substantially contaminated by response
      bias. The sensitivity index d', calculated according to detection theory,
      provided reasonable and unbiased performance versus intensity functions.
      CONCLUSIONS: The results firstly indicate that the material is homogenous enough
      for use as a speech test in clinical work and research. Secondly, to assess the
      discrimination performance for individual tones, d' values outperform the simple
      proportion of correct responses.

PMID- 21091263
TI  - Phospholipase C beta 1 expression in the dorsolateral prefrontal cortex from
      patients with schizophrenia at different stages of illness.
AB  - OBJECTIVE: Our recent microarray study detected decreases in the expression of
      phospholipase C beta 1 mRNA in the dorsolateral prefrontal cortex from subjects
      with schizophrenia at different stages of illness. Thus we aimed to validate and
      extend these findings. METHOD: We measured levels of mRNA and protein for
      phospholipase C beta 1 variant a and b using real-time PCR and western blot
      analysis, respectively, in the dorsolateral prefrontal cortex from subjects with
      schizophrenia, who had a short (< 7 years) or long (> 22 years) duration of
      illness. RESULTS: Compared to age/sex matched controls, levels of phospholipase C
      beta 1 variant a and b mRNAs were decreased (-33% and -50%, respectively) in
      short duration schizophrenia. By contrast, only variant a mRNA was decreased (
      24%) in long duration schizophrenia. There was no significant difference in the
      protein levels of either phospholipase C beta 1 variant in schizophrenia,
      irrespective of duration of illness (variant a; P = 0.84, variant b; P = 0.73).
      CONCLUSION: Our data confirm that phospholipase C beta 1 transcript levels are
      decreased in the dorsolateral prefrontal cortex from subjects with schizophrenia.
      However, the changes in levels of mRNA do not translate into a change at the
      level of protein. It is possible protein expression is regulated independently of
      mRNA and it remains to be determined whether there is a functional consequence of
      this change in mRNA relating to the pathophysiology of schizophrenia.

PMID- 21091264
TI  - Genetically modified donor leukocyte transfusion and graft-versus-leukemia effect
      after allogeneic stem cell transplantation.
AB  - Seven patients with acute myeloid leukemia (AML) and two patients with chronic
      myelogenous leukemia (CML) were transplanted from HLA-identical sibling donors
      with CD34(+) cell-enriched stem cells (HSCTs) without further immunosuppression.
      The myeloablative standard transplantation protocol was adapted to include
      transfusion of gene-modified donor T cells after HSCT. Donor T cells were
      transduced with the replication-deficient retrovirus SFCMM-3, which expresses
      herpes simplex thymidine kinase (HSV-Tk) and a truncated version of low-affinity
      nerve growth factor receptor (DeltaLNGFR) for selection and characterization of
      transduced cells. Transduced T cells were detectable in all patients during
      follow-up for up to 5 years after transfusion. Proteomic screening for
      development of acute graft-versus-host disease (aGvHD) was applied to five of the
      seven patients with AML. No positivity for the aGvHD grade II-specific proteomic
      pattern was observed. Only one patient developed aGvHD grade I. To date, three of
      the patients with AML relapsed; one responded to three escalating transfusions of
      lymphocytes from the original donor and is in complete remission. Two were
      retransplanted with non-T cell-depleted peripheral blood stem cells from their
      original donors and died after retransplantation of septic complications or
      relapse, respectively. In one patient with CML, loss of bcr-abl gene expression
      was observed after an expansion of transduced cells. Seven of nine patients are
      alive and in complete remission.

PMID- 21091265
TI  - Biological variation of free beta chorionic gonadotropin and pregnancy-associated
      plasma protein A in first trimester pregnancies.
AB  - BACKGROUND: Trisomy 21 risk estimation in first trimester pregnancies can be
      performed by a combined test based on ultrasound measurement of fetal nuchal
      translucency thickness and maternal plasma concentrations of free beta human
      chorionic gonadotropin (hCGbeta) and pregnancy-associated plasma protein A (PAPP
      A). However, little knowledge exists regarding the biological variation of
      hCGbeta and PAPP-A when the time interval between sampling increases. METHODS: We
      estimated these variations from double measurements of hCGbeta and PAPP-A in
      first trimester pregnancies in 167 women. Data were divided into three groups
      based on the number of days between sampling. The correlation coefficients and
      biological variation were estimated for each group. RESULTS: The correlation
      coefficient between the first and second samples was 0.841 for hCGbeta, and 0.706
      for PAPP-A. The ranges for biological variation were 11.9%-48.5% for hCGbeta and
      31.6%-63.3% for PAPP-A, increasing with time between sampling. The average
      overall biological variation for hCGbeta was 29%, and 49.7% for PAPP-A.
      CONCLUSIONS: We found high biological variation for plasma concentrations of
      hCGbeta and PAPP-A, increasing with longer time intervals between sampling. From
      our data that showed high correlation of hCGbeta and PAPP-A in the first and
      second sample, we found no reason to recommend retesting. However, new studies
      should clarify whether PAPP-A should be collected early, and hCGbeta late, in the
      first trimester of pregnancy.

PMID- 21091266
TI  - Abstracts of Neurofly 2010 (the 13th European Drosophila Neurobiology
      Conference). September 1-3, 2010. Manchester, United Kingdom.

PMID- 21091267
TI  - Intracranial pressure increases during exposure to a shock wave.
AB  - Traumatic brain injuries (TBI) caused by improvised explosive devices (IEDs)
      affect a significant percentage of surviving soldiers wounded in Iraq and
      Afghanistan. The extent of a blast TBI, especially initially, is difficult to
      diagnose, as internal injuries are frequently unrecognized and therefore
      underestimated, yet problems develop over time. Therefore it is paramount to
      resolve the physical mechanisms by which critical stresses are inflicted on brain
      tissue from blast wave encounters with the head. This study recorded direct
      pressure within the brains of male Sprague-Dawley rats during exposure to blast.
      The goal was to understand pressure wave dynamics through the brain. In addition,
      we optimized in vivo methods to ensure accurate measurement of intracranial
      pressure (ICP). Our results demonstrate that proper sealing techniques lead to a
      significant increase in ICP values, compared to the outside overpressure
      generated by the blast. Further, the values seem to have a direct relation to a
      rat's size and age: heavier, older rats had the highest ICP readings. These
      findings suggest that a global flexure of the skull by the transient shockwave is
      an important mechanism of pressure transmission inside the brain.

PMID- 21091268
TI  - Hippocampal neurogenesis after traumatic brain injury is mediated by vascular
      endothelial growth factor receptor-2 and the Raf/MEK/ERK cascade.
AB  - Adult neurogenesis occurs in the subgranular zone of the hippocampal dentate
      gyrus, and can be modulated by physiological and pathological events. We examined
      the effect of vascular endothelial growth factor (VEGF), and the correlation
      between VEGF and the Raf/MEK/ERK cascade in neurogenesis after traumatic brain
      injury (TBI). The expression of VEGF and the phosphorylation level of Raf/MEK/ERK
      were analyzed by Western blot, and TBI-induced neurogenesis was determined by
      immunofluorescence labeling and confocal microscopic detection. Hippocampal VEGF
      began to increase after 12 h, and reached a peak at day 7. Along with the
      upregulation of VEGF, neurogenesis in the hippocampus also increased.
      Administration of the VEGF antisense oligodeoxynucleotide, or the VEGF receptor-2
      antagonist SU1498 (10 MUg, ICV), attenuated the phosphorylation of the MAPK
      cascade proteins and caused a decrease in neurogenesis in the hippocampus.
      Similarly, administration of the ERK inhibitor PD98059 (500 ng, ICV) also
      exhibited a suppressive effect on neurogenesis. Our results indicate that VEGF
      plays an important role in neurogenesis after TBI, and that the process involves
      VEGF receptor-2 and the Raf/MEK/ERK cascade.

PMID- 21091269
TI  - Clevidipine for severe hypertension in patients with renal dysfunction: a
      VELOCITY trial analysis.
AB  - INTRODUCTION: Acute and severe hypertension is common, especially in patients
      with renal dysfunction (RD). Clevidipine is a rapidly acting (t1/2~1 min)
      intravenous (IV) dihydropyridine calcium-channel blocker metabolized by blood and
      tissue esterases and may be useful in patients with RD. The purpose of this
      analysis was to assess the safety and efficacy of clevidipine in patients with
      RD. METHODS: VELOCITY, a multicenter open-label study of severe hypertension,
      enrolled 126 patients with persistent systolic blood pressure (SBP) >180 mmHg.
      Investigators pre-specified a SBP initial target range (ITR) for each patient to
      be achieved within 30 min. Blood pressure monitoring was by cuff. Clevidipine was
      infused via peripheral IV at 2 mg/h for at least 3 min, then doubled every 3 min
      as needed to a maximum of 32 mg/h (non-weight-based treat-to-target protocol).
      Per protocol, clevidipine was continued for at least 18 h (96 h maximum). RD was
      diagnosed and reported as an end-organ injury by the investigator and was defined
      as requiring dialysis or an initial creatinine >2.0 mg/dl. Primary endpoints were
      the percentage of patients within the ITR by 30 min and the percentage below the
      ITR after 3 min of clevidipine infusion. RESULTS: Of the 24 patients with
      moderate to severe RD, most (13/24) were dialysis dependent. Forty-six percent
      were male, with mean age 51 +/- 14 years; 63% were black and 96% had a
      hypertension history. Median time to achieve the ITR was 8.5 min. Almost 90% of
      patients reached the ITR in 30 min without evidence of overshoot and were
      maintained on clevidipine through 18 h. Most patients (88%) transitioned to oral
      antihypertensive therapy within 6 h of clevidipine termination. CONCLUSIONS: This
      report is the first demonstrating that clevidipine is safe and effective in RD
      complicated by severe hypertension. Prolonged infusion maintained blood pressure
      within a target range and allowed successful transition to oral therapy.

PMID- 21091271
TI  - Comparability of haemoglobin mass measured with different carbon monoxide-based
      rebreathing procedures and calculations.
AB  - BACKGROUND: Measurements of haemoglobin mass (Hb(mass)) with the carbon monoxide
      (CO) rebreathing method provide valuable information in the field of sports
      medicine, and have markedly increased during the last decade. However, several
      different approaches (as a combination of the rebreathing procedure and
      subsequent calculations) for measuring Hb(mass) are used, and routine
      measurements have indicated that the Hb(mass) differs substantially among various
      approaches. Therefore, the aim of this study was to compare the Hb(mass) of the
      seven most commonly used approaches, and then to provide conversion factors for
      an improved comparability of Hb(mass) measured with the different approaches.
      METHODS: Seventeen subjects (healthy, recreationally active, male, age 27.1 +/-
      1.8 y) completed 3 CO-rebreathing measurements in randomized order. One was based
      on the 12-min original procedure (CO(original)), and two were based on the 2-min
      optimized procedure (CO(new)). From these measurements Hb(mass) for seven
      approaches (CO(originalA-E); CO(newA-B)) was calculated. RESULTS: Hb(mass)
      estimations differed among these approaches (p < 0.01). Hb(mass) averaged 960 +/-
      133 g (CO(newB)), 981 +/- 136 g (CO(newA)), 989 +/- 130 g (CO(originalE)), 993 +/
      126 g (CO(originalA,D)), 1030 +/- 130 g (CO(originalB)), and 1053 +/- 133 g
      (CO(originalC)). Procedural variations had a minor influence on measured
      Hb(mass). CONCLUSIONS: The relevant discrepancies between the CO-rebreathing
      approaches originate mainly from different underlying calculations for Hb(mass).
      Provided Hb(mass) enabled the development of conversion factors to compare
      average Hb(mass) values measured with different CO-rebreathing approaches. These
      factors can be used to develop reasonable Hb(mass) reference ranges for both
      clinical and athletic purposes.

PMID- 21091270
TI  - Antihypertensive efficacy and safety of olmesartan and ramipril in elderly
      patients with mild to moderate systolic and diastolic essential hypertension.
AB  - OBJECTIVE: To compare the efficacy and safety of olmesartan medoxomil (O) and
      ramipril (R) in elderly patients with essential arterial hypertension. METHODS:
      After a 2-week placebo washout, 351 elderly hypertensive patients aged 65-89
      years (office sitting diastolic blood pressure, DBP, 90-109 mmHg and office
      sitting systolic blood pressure, SBP, 140-179 mmHg) were randomized double-blind
      to 12-week treatment with O 10 mg or R 2.5 mg once daily. After the first 2 and 6
      weeks, doses could be doubled in non-normalized (blood pressure <140/90 mmHg for
      non-diabetic and <130/80 mmHg for diabetic) subjects, up to 40 mg for O and 10 mg
      for R. Office blood pressures were assessed at randomization, after 2, 6 and 12
      weeks of treatment; 24-h ambulatory blood pressure (ABP) was recorded at
      randomization and after 12 weeks. RESULTS: At week 12, in the intention-to-treat
      population (170 patients O and 175 R) the rate of normalized subjects was
      significantly larger in the O group (38.8% vs 26.3% R; p = 0.013). Baseline
      adjusted mean sitting office blood pressure reduction at final visit was not
      significantly greater under O [SBP: 16.6 (95% confidence interval 14.0/19.2) mmHg
      vs 13.0 (10.4/15.6) mmHg R, p = 0.206; DBP: 11.8 (10.3/13.3) mmHg vs 10.5
      (9.0/12.0) mmHg, p = 0.351]. In the subgroup of patients with valid ABP
      recordings (38 O and 47 R), the reduction in 24-h average blood pressure was
      significantly (p < 0.01) larger with O [SBP: 8.9 (9.8/8.1) and DBP: 5.7 (6.3/5.1)
      mmHg] than with R [6.7 (7.9/5.6) and 4.4 (5.1/3.7) mmHg]. The superiority of O
      was particularly evident in the last 4 h from the dosing interval. The proportion
      of patients with drug-related adverse events was comparable in the two groups
      (4.0% O vs 4.5% R), as well as the number of patients discontinuing study drug
      because of a side-effect (8 O vs 7 R). CONCLUSIONS: In elderly patients with
      essential arterial hypertension, O provides an effective, prolonged and well
      tolerated blood pressure control, with significantly better blood pressure
      normalization than R and represents a useful option among first-line drug
      treatments of hypertension in this age group.

PMID- 21091273
TI  - Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI
      contrast agent.
AB  - A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver
      was developed by conjugation of gadolinium (Gd) chelate groups onto the
      biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG)
      nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA)
      was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and
      then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on
      the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles
      was 265.9 +/- 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was
      measured, and the distribution in vivo was evaluated in rats. Compared with
      conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles
      showed significant enhancement both on liver targeting ability and imaging signal
      intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled
      nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T,
      respectively. In addition, the signal intensity in vivo was stronger comparing
      with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver
      targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57
      comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles
      showed the potential as targeting molecular MRI contrast agent for further
      clinical utilization.

PMID- 21091272
TI  - Differential effects of injury severity on cognition and cellular pathology after
      contusive brain trauma in the immature rat.
AB  - Although diffuse brain damage has been suggested to be the predominant predictor
      of neurological morbidity following closed head injury in infants and children,
      the presence of contusions also predicts long-term neurobehavioral dysfunction.
      Contusive brain trauma in the 17-day-old rat resulted in neurodegeneration and
      caspase activation in the cortex at 1 day, and in the thalamus at 3 days post
      injury, and to a greater extent following a deeper impact. Cortical tissue loss
      in the 4-mm impact group was significantly greater than that in the 3-mm impact
      group (p < 0.05), and exhibited a time-dependent increase over the first 3 weeks
      post-injury. Traumatic axonal injury was observed in the white matter tracts
      below the site of impact at 1 day, and in the corpus callosum at 3 days, to a
      greater extent following 4-mm impact. In contrast, cellular caspase-3 activation
      in these white matter tracts was only observed at 24 h post-injury and was not
      affected by impact depth. Similarly, neurodegeneration and caspase activation in
      the hippocampus was restricted to the dentate gyrus and occurred to a similar
      extent in both injured groups. Only the 4-mm impact group exhibited learning
      deficits in the first week (p < 0.0001) that was sustained until the third week
      post-injury (p < 0.0001), while deficits in the 3-mm impact group were seen only
      at 3 weeks post-injury (p < 0.02). These observations demonstrate that increasing
      severity of injury in immature animals does not uniformly increase the extent of
      cellular damage, and that the progression of tissue damage and behavioral
      deficits varies as a function of injury severity.

PMID- 21091274
TI  - Transient depletion of kupffer cells leads to enhanced transgene expression in
      rat liver following retrograde intrabiliary infusion of plasmid DNA and DNA
      nanoparticles.
AB  - In this report, we have demonstrated that by temporarily removing Kupffer cells
      (KCs), the transgene expression levels mediated by retrograde intrabiliary
      infusion (RII) of plasmid DNA, polyethylenimine-DNA, and chitosan nanoparticles
      were enhanced by 1,927-, 131-, and 23,450-fold, respectively, in comparison with
      the respective groups without KC removal. KC removal also led to significantly
      prolonged transgene expression in the liver that received all three carriers.
      This increased transgene expression was correlated with significantly reduced
      serum tumor necrosis factor-alpha level as an indicator for KC activation. These
      results suggest that KC activation is a significant contributing factor to the
      lowered transgene expression by polycation-DNA nanoparticles delivered by RII.
      More importantly, the combination of RII and transient removal of KCs may be
      adopted as an effective approach to achieving high and persistent transgene
      expression in the liver mediated by nonviral nanoparticles.

PMID- 21091275
TI  - Ultrasonography shows significant improvement in wrist and ankle tenosynovitis in
      rheumatoid arthritis patients treated with adalimumab.
AB  - OBJECTIVE: Tenosynovitis is common in rheumatoid arthritis (RA) but knowledge is
      limited regarding its response to anti-inflammatory treatment. This study used
      ultrasonography (US) to examine the distribution and responsiveness of
      tenosynovitis to anti-tumour necrosis factor (anti-TNF) treatment in RA patients.
      METHODS: Twenty patients with RA were examined at baseline and 1, 3, 6, and 12
      months after starting adalimumab treatment, and grey-scale (GS) and power Doppler
      (PD) US scoring (semi-quantitative range 0-3) of wrist and ankle tendons was
      performed in addition to assessment of the 28-joint Disease Activity Score
      (DAS28), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
      RESULTS: The extensor carpi ulnaris (ECU) tendon in the wrists and the closely
      related tendons tibialis posterior (TB) and flexor digitorum longus (FDL) in the
      ankles were most often inflamed. Median sum scores for this reduced number of
      tendons at baseline/12-month follow-up were 5/0.5 for GS (p < 0.001) and 4/0 for
      PD (p < 0.05), with reductions in the US scores during follow-up as large as
      those found for sum scores of all tendons. The standardized response means (SRMs)
      for sum GS or PD scores of the reduced number of tendons were higher (range -0.53
      to -0.93) than for the sum scores of all tendons (-0.23 to -0.74), and showed
      larger responsiveness than CRP (-0.10 to -0.43) and ESR (-0.03 to -0.71).
      CONCLUSION: Bilateral assessments of ECU, TB, and FDL tendons were as sensitive
      to change as the sum scores of all tendons, and scoring of this reduced number of
      tendons is suggested to be included in US scorings for follow-up of RA patients.

PMID- 21091276
TI  - Critical physiological and surgical considerations for hydrodynamic
      pressurization of individual segments of the pig liver.
AB  - Hydrodynamic gene delivery to the liver is a promising approach for liver gene
      therapy in the clinic, but levels of gene expression in larger species have been
      much less than in rodents. The development of surgical techniques for
      pressurizing individual liver segments and the establishment of whether hepatic
      vascular anatomy in fact permits pressurization of individual segments are
      critical issues that need to be addressed. We have evaluated these issues using
      hydrodynamic delivery to individual segments of the pig liver, via branches of
      both portal and hepatic veins. Our objective was to develop surgical techniques
      that achieve elevated vascular pressures within individual liver segments with
      small volumes, but without interruption of portal blood flow or reduction in
      venous return to the heart. We report that, without specific surgical
      interventions to obstruct outflow of DNA solution from the targeted liver
      segment, little or no increase in intrahepatic vascular pressure occurs. We
      demonstrate, for the first time, that selective pressurization of individual
      liver segments is possible without compromising portal venous flow or venous
      return to the heart. Thus, hydrodynamic gene delivery to individual liver
      segments is technically achievable in a clinical setting, but will require open
      abdominal surgery rather than minimally invasive techniques.

PMID- 21091277
TI  - The ABCG2 transporter and its relations with the pharmacokinetics, drug
      interaction and lipid-lowering effects of statins.
AB  - IMPORTANCE OF THE FIELD: The ABCG2 efflux transporter is expressed in multiple
      tissues and plays an important role in the disposition of many statins. The
      functional 421C>A polymorphism in ABCG2 that reduces transporter activity has
      been found to be associated with increased systemic exposures to certain statins.
      AREAS COVERED IN THIS REVIEW: We review and evaluate the associations of the
      ABCG2 polymorphism on the pharmacokinetics and clinical efficacy of statins. WHAT
      THE READER WILL GAIN: This article gives a detailed overview of the ABCG2
      transporter and extensively reviews its relations with the pharmacokinetics and
      lipid-lowering effects of statins. This review also discusses the potential role
      of the ABCG2 polymorphism in the clinical outcomes in statin-treated patients and
      statin-drug interactions. TAKE HOME MESSAGE: The impact of the ABCG2 421C>A
      polymorphism on the disposition of the statins varies between different drugs and
      the effect on systemic exposure was greater in the case of rosuvastatin than
      other statins. This genetic variant was associated with greater low-density
      lipoprotein cholesterol response to rosuvastatin in Chinese and caucasian
      patients. The effect of the ABCG2 421C>A polymorphism on the lipid response to
      other substrate statins and clinical outcomes need to be evaluated in future
      studies.

PMID- 21091278
TI  - Long-term effect of latanoprost on central corneal thickness in normal tension
      glaucoma.
AB  - PURPOSE: To evaluate the long-term effect of latanoprost on central corneal
      thickness (CCT) in patients with normal tension glaucoma (NTG). METHODS: This was
      a retrospective study and included 166 eyes of 166 patients [128 with NTG and 38
      with glaucoma suspect, suspicious discs with normal visual fields, and an
      intraocular pressure (IOP) <=21  mmHg as the control group]. Patients with newly
      diagnosed NTG and who had not had previous topical glaucomatous treatment were
      followed >=24 months and received latanoprost 0.005% monotherapy once a day. CCT
      measurements were performed with an ultrasound pachymeter. CCT measurements
      before treatment and 24 months after treatment were analyzed. RESULTS: There were
      no significant differences between the latanoprost group and the control group
      with respect to sex, age, baseline IOP, and CCT. A statistically significant
      reduction in the mean CCT was observed in the latanoprost group [535.5 +/- 37.9
      vs. 530.1 +/- 36.4  MUm (n = 128), P < 0.01], but not in the control group [543.1
      +/- 40.2 vs. 542.6 +/- 37.0  MUm (n = 38), P = 0.786]. CONCLUSIONS: Long-term use
      of latanoprost may decrease the CCT in patients with NTG. Therefore, clinicians
      must be aware of longitudinal CCT variations that may arise throughout the follow
      up period for proper IOP targeting and management.

PMID- 21091280
TI  - Oral preexposure prophylaxis for HIV--another arrow in the quiver?

PMID- 21091281
TI  - Kinetics of inflammatory markers following cancer-related bowel and liver
      resection.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) was originally described
      as a cytokine that inhibits migration of macrophages at the site of inflammation.
      Subsequently it was also identified as a stress-induced hormone released from the
      anterior pituitary lobe in response to some pro-inflammatory stimuli like
      endotoxins and tumour necrosis factor (TNF-alpha). AIM: To compare postoperative
      changes in serum MIF levels of patients undergoing bowel and liver resections. It
      has clinical relevance to describe the kinetics of this crucial mediator of
      systemic inflammation in surgery. METHODS: A total of 58 patients were studied
      over 4 years. Group A (28 patients) underwent only hepatic resection without
      enterotomy. Group B (30 patients) had bowel resection with enterotomy. MIF, IL
      1beta, IL-8, prealbumin, albumin, alpha1-glycoprotein, fibrinogen, and C-reactive
      protein levels were measured preoperatively, immediately following surgery, and
      postoperatively for three consecutive days. To evaluate organ functions, multiple
      organ dysfunction score was used. RESULTS: A significantly higher level of MIF
      (4,505 pg/mL) was found in group A when compared to that of group B immediately
      following surgery. Other parameters monitored in this study were not
      statistically different between the two groups. CONCLUSION: Higher elevations in
      MIF levels with liver resections, compared to bowel resections, might be
      attributable to MIF release from damaged liver cells. The presumably minimal
      endotoxin exposure during bowel surgery was either insufficient or inefficient to
      induce relevant MIF elevations in our patients. To fully delineate implications
      of this finding further studies are needed.

PMID- 21091282
TI  - Characterization of a transgenic short hairpin RNA-induced murine model of
      Tafazzin deficiency.
AB  - Barth's syndrome (BTHS) is an X-linked mitochondrial disease that is due to a
      mutation in the Tafazzin (TAZ) gene. Based on sequence homology, TAZ has been
      characterized as an acyltransferase involved in the metabolism of cardiolipin
      (CL), a unique phospholipid almost exclusively located in the mitochondrial inner
      membrane. Yeast, Drosophila, and zebrafish models have been invaluable in
      elucidating the role of TAZ in BTHS, but until recently a mammalian model to
      study the disease has been lacking. Based on in vitro evidence of RNA-mediated
      TAZ depletion, an inducible short hairpin RNA (shRNA)-mediated TAZ knockdown
      (TAZKD) mouse model has been developed (TaconicArtemis GmbH, Cologne, Germany),
      and herein we describe the assessment of this mouse line as a model of BTHS. Upon
      induction of the TAZ-specific shRNA in vivo, transgenic mouse TAZ mRNA levels
      were reduced by >89% in cardiac and skeletal muscle. TAZ deficiency led to the
      absence of tetralineoyl-CL and accumulation of monolyso-CL in cardiac muscle.
      Furthermore, mitochondrial morphology from cardiac and skeletal muscle was
      altered. Skeletal muscle mitochondria demonstrated disrupted cristae, and cardiac
      mitochondria were significantly enlarged and displace neighboring myofibrils.
      Physiological measurements demonstrated a reduction in isometric contractile
      strength of the soleus and a reduction in cardiac left ventricular ejection
      fraction of TAZKD mice compared with control animals. Therefore, the inducible
      TAZ-deficient model exhibits some of the molecular and clinical characteristics
      of BTHS patients and may ultimately help to improve our understanding of BTHS
      related cardioskeletal myopathy as well as serve as an important tool in
      developing therapeutic strategies for BTHS.

PMID- 21091284
TI  - What are you prepared to do?

PMID- 21091283
TI  - Rapidly progressive dementias and the treatment of human prion diseases.
AB  - IMPORTANCE OF THE FIELD: Rapidly progressive dementia (RPD) has many possible
      etiologies and definitive treatment is reliant upon an accurate diagnosis from an
      appropriate diagnostic work-up. A large portion of the neurodegenerative causes
      of RPD are due to prion diseases (e.g., Creutzfeldt-Jakob disease). The study of
      prion diseases, for which there is no currently available treatment, has public
      health implications and is becoming increasingly more relevant to our
      understanding of other protein misfolding disorders including Alzheimer's
      disease, frontotemporal degeneration, and Parkinson's disease. AREAS COVERED IN
      THIS REVIEW: This article begins with an overview of the etiologies and
      diagnostic work-up of RPD followed by a detailed review of the literature
      concerning the treatment of human prion diseases (1971 to present). WHAT THE
      READER WILL GAIN: The reader will understand the differential diagnosis and work
      up of RPD as it pertains to its treatment, as well as an in-depth understanding
      of treatments of human prion diseases. TAKE HOME MESSAGE: An accurate diagnosis
      of the cause of RPD is of paramount importance when determining appropriate
      treatment. Most studies of the treatment for human prion diseases are case
      reports or case series, and results from only one randomized, placebo-controlled
      study have been reported in the literature (flupirtine). Studies have been
      hindered by disease heterogeneity and lack of standardized outcome measures.
      Although no effective prion disease treatment has been revealed through these
      studies, they provide important considerations for future studies.

PMID- 21091285
TI  - Expanding access to telespeech in clinical settings: inroads and challenges.

PMID- 21091286
TI  - A review of efficacious technology-based weight-loss interventions: five key
      components.
AB  - OBJECTIVE: Obesity is highly prevalent among American adults and has negative
      health and psychosocial consequences. The purpose of this article was to
      qualitatively review studies that used technology-based interventions for weight
      loss and to identify specific components of these interventions that are
      effective in facilitating weight loss. MATERIALS AND METHODS: We conducted a
      narrow, qualitative review, focusing on articles published in the last 10 years
      that used an experimental or pre/posttest design and used a technology-based
      intervention for weight loss. RESULTS: Among the 21 studies reviewed, we
      identified the following five components that we consider to be crucial in
      technology-based weight-loss interventions that are successful in facilitating
      weight loss: self monitoring, counselor feedback and communication, social
      support, use of a structured program, and use of an individually tailored
      program. CONCLUSIONS: Short-term results of technologically driven weight-loss
      interventions using these components have been promising, but long-term results
      have been mixed. Although more longitudinal studies are needed for interventions
      implementing these five components, the interface of technology and behavior
      change is an effective foundation of a successful, short-term weight-loss program
      and may prove to be the basis of long-term weight loss.

PMID- 21091287
TI  - Knowledge of computer among healthcare professionals of India: a key toward e
      health.
AB  - Information technology has radically changed the way that many people work and
      think. Over the years, technology has touched a new acme and now it is not
      confined to developed countries. Developing countries such as India have kept
      pace with the world in modern technology. Healthcare professionals can no longer
      ignore the application of information technology to healthcare because they are
      key to e-health. This study was conducted to enlighten the perspective and
      implications of computers among healthcare professionals, with the objective to
      assess the knowledge, use, and need of computers among healthcare professionals.
      A cross-sectional study of 240 healthcare professionals, including doctors,
      nurses, lab technicians, and pharmacists, was conducted. Each participant was
      interviewed using a pretested, semistructured format. Of 240 healthcare
      professionals, 57.91% were knowledgeable about computers. Of them, 22.08% had
      extensive knowledge and 35.83% had partial knowledge. Computer knowledge was
      greater among the age group 20-25 years (high knowledge-43.33% and partial
      knowledge-46.66%). Of 99 males, 21.21% were found to have good knowledge and
      42.42% had partial knowledge. A majority of doctors and nurses used computer for
      study purposes. The remaining healthcare professionals used it basically for the
      sake of entertainment, Internet, and e-mail. A majority of all healthcare
      professionals (95.41%) requested computer training, which according to them would
      definitely help to make their future more bright and nurtured as well as to
      enhance their knowledge regarding computers.

PMID- 21091288
TI  - Age-specific stabilization in obesity prevalence in German children: a cross
      sectional study from 1999 to 2008.
AB  - OBJECTIVE: Trends of overweight (ov)/obesity (ob) prevalence among German
      children aged 4-16 years were studied between 1999 and 2008. SUBJECTS: Body mass
      index (BMI) data (>P90 [ov] and >P97 [ob]) from the national CrescNet database
      were analysed in three age groups: 4-7.99, 8-11.99, and 12-16 years. RESULTS:
      Trend analyses. Data from 272 826 children were analyzed. a) Whole study
      population aged 4-16 years old. A significant upward trend for ov/ob prevalence
      was found between 1999 and 2003, and a significant downward trend between 2004
      and 2008. b) Subgroup analyses. Ov/Ob prevalence increased in most subgroups
      studied until 2004. Between 2004 and 2008, a downward trend for ov/ob prevalence
      was found in children, aged 4-7.99 years, whereas it stabilized in most other
      subgroups studied. Cross-sectional analyses. Data from 93 028 children were
      analyzed. Ov/ob prevalence was significantly higher in 2004 compared with 2000 in
      girls aged 12-16 years and in boys aged 8-16 years. Ov/ob obesity prevalence was
      significantly lower in 2008 compared with 2004 in children aged 4-7.99 years.
      CONCLUSION: Ov/ob prevalence increased between 1999 and 2003 in German children.
      Since 2004, this trend has been stabilizing or turning into a downward trend. Our
      data confirm the global trend of stabilizing prevalence rates of childhood
      obesity at a high level and add important information for individual age groups.
      Intervention programs targeted to prevent childhood obesity may have had
      beneficial effects, and a new balance between factors favouring obesity and those
      favouring leanness may have been reached recently. Age- and gender-specific
      differences found in trends of ov/ob prevalence may help optimise preventive and
      therapeutic measures.

PMID- 21091289
TI  - Percutaneous penetration characteristics and release kinetics of contact
      allergens encapsulated in ethosomes.
AB  - BACKGROUND: Formulation of the contact allergens dinitrochlorobenzene and
      isoeugenol in ethanolic liposomes (ethosomes) increases their sensitizing
      properties in the local lymph node assay compared with an ethanol-water
      formulation of the allergens. Likewise, isoeugenol and methyldibromo
      glutaronitrile formulated in ethosomes enhanced the patch test reactions in
      sensitized human volunteers. The relationship between the percutaneous
      penetration/absorption and sensitization/elicitation phases of contact allergy is
      not well elucidated. OBJECTIVE: The aim of this study was to investigate whether
      the observed increased sensitizing and elicitation properties following the
      formulation of selected contact allergens in ethosomes could be explained by a
      change in release kinetics of the allergens and their pattern of percutaneous
      penetration and absorption as well as allergen deposition in epidermis and
      dermis. METHODS: Release kinetics were studied using dialysis bags, and samples
      were taken at selected time points until equilibrium was reached. Percutaneous
      absorption and penetration were studied using human skin on Franz cells, and
      receptor fluid samples were taken at selected time points. Experiments were
      terminated after 24 hours, and deposition of allergen in epidermis and dermis was
      measured. Maximum flux and lag time were calculated. RESULTS: Ethosome
      formulation decreased the release of both allergens compared with the ethanol
      water formulation. Ethosome formulation of dinitrochlorobenzene increased its
      percutaneous penetration but reduced the percutaneous penetration of isoeugenol
      compared with control formulations. Likewise, all other calculated parameters
      showed an opposite trend for the 2 allergens in ethosomes and ethanol-water.
      CONCLUSIONS: The present study demonstrates that identical ethosomes affect the
      percutaneous penetration characteristics of 2 allergens differently. Thus, our
      results indicate that each combination of an allergen and a vehicle needs to be
      evaluated separately. The exact mechanistic relationship between percutaneous
      penetration, release kinetics, and allergenicity of chemicals in various vehicles
      remains to be clarified.

PMID- 21091290
TI  - Prospective meta-analysis within complementary medicine research.

PMID- 21091292
TI  - Nutraceutical composition of Zizyphus mauritiana Lamk (Indian ber): effect of
      enzyme-assisted processing.
AB  - Zizyphus (Indian ber) is an excellent source of several phenolic compounds. The
      effect of two cell wall degrading enzymes, namely pectinase and viscozyme, on the
      nutraceutical composition of Zizyphus juice was investigated in the present
      study. Enzyme assisted processing significantly (P < 0.05) improved the juice
      yield, total soluble solids, total phenolics and total antioxidant activity
      (AOX). There was significant increase in recovery of antioxidants, to the tune of
      70.51%, 66%, and 45% respectively in ascorbic acid, total phenolics and total
      flavonoids through viscozyme. The in-vitro total AOX of juice extracted via
      enzyme-assisted processing was 20.9 and 15.59 MUmol Trolox/ml in ferric-reducing
      antioxidant power and cupric-reducing antioxidant capacity assays, respectively.
      There was 41% increase in AOX of juice extracted with enzyme over straight
      pressed juice. Results indicate that enzyme-assisted processing can significantly
      improve the functional properties of the Zizyphus juice.

PMID- 21091293
TI  - Effects of chicory inulin in constipated elderly people: a double-blind
      controlled trial.
AB  - The impact of the daily consumption of 15 g chicory native inulin on fecal levels
      of bifidobacteria, stool parameters and quality of life of elderly constipated
      volunteers was investigated in a randomized, double-blind, controlled versus
      placebo clinical trial. The impact of supplementation on constipation was
      assessed with questionnaires on bowel motor function parameters, visual analogue
      scales on bowel symptoms and quality of life. Fecal bacteria counts were
      determined at the beginning and at the end of the supplementation. Inulin
      supplementation led to a significant increase in total fecal bacteria (P < 0.01)
      and bifidobacteria (P < 0.001) concentrations after 28 days of consumption.
      Volunteers (n = 25) in the inulin group reported increased satisfaction about
      digestion (P < 0.01) and reduced defecation difficulties (P < 0.001) during the
      supplementation. Slight gastrointestinal symptoms (flatulence) were reported but
      did not lead to discontinuation. Daily supplementation with 15 g inulin improves
      constipation and quality of life in an elderly population with constipation.

PMID- 21091294
TI  - The effect of trataka, a yogic visual concentration practice, on critical flicker
      fusion.
AB  - OBJECTIVES: The study objective was to study the change in the critical flicker
      fusion (CFF) after a yogic visual concentration practice (trataka). DESIGN:
      Thirty (30) subjects participated in a study where they were evaluated for the
      CFF immediately before and after the practice. The subjects also participated in
      a comparable control session. SUBJECTS: The subjects were 30 volunteers in the
      age range 25-40. Fifteen (15) of the volunteers were male. The mean age was 31.33
      +/- 4.67. RESULTS: The CFF showed a statistically significant increase from 37.35
      +/- 2.84 to 38.66 +/- 2.91 after the yoga practice of trataka. The control
      session did not produce a statistically significant change in the CFF.
      CONCLUSIONS: An increase in the CFF is seen immediately after the yogic
      concentration practice called trataka.

PMID- 21091291
TI  - Natural regulatory T cells in autoimmunity.
AB  - The suppressive/immunomodulatory function of CD4(+)CD25(+)FOXP3(+) regulatory T
      (Treg) cells is crucial for the maintenance of immune homeostasis, which helps to
      prevent autoimmunity and reduce the inflammation induced by pathogens and
      environmental insults. This review summarizes the current knowledge on the types
      and mechanisms of action of Treg cells and their role in the immune tolerance to
      self-antigens, with a particular focus on naturally occurring Treg cells.

PMID- 21091295
TI  - Effect of compositional alteration of food matrices and processing on
      availability of selected nutrients and bioactive components in rice products.
AB  - The aim was to determine the influence of compositional alteration and processing
      on the digestibility/availability of nutrients and bioactive components [protein
      (IVPD), starch (IVSD), iron, calcium, polyphenols, flavonoids] in rice products.
      The compositional changes representing fortified foods in 'wafers' and 'noodles'
      were addition of iron, rice bran, onion and cabbage. The moisture content of
      wafer and noodles ranged from 4.1 to 4.8% and from 73.3 to 82.1%, respectively.
      Wafer control (73.9-75.9%) and noodle with iron and control (85.4-87.0%) showed
      the highest IVPD and IVSD. Addition of rice bran decreased nutrient
      digestibility. The control and iron-added products exhibited least and highest
      available iron (2.50-2.69% and 5.99-7.07%). Total and available bioactive
      components increased in proportion to added external source. Overall availability
      of all components was better in noodles than in wafers, indicating high moisture
      supported higher availability. In conclusion, it can be said that both
      composition of the food matrix and processing influenced the availability of
      analyzed components.

PMID- 21091279
TI  - Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.
AB  - BACKGROUND: Antiretroviral chemoprophylaxis before exposure is a promising
      approach for the prevention of human immunodeficiency virus (HIV) acquisition.
      METHODS: We randomly assigned 2499 HIV-seronegative men or transgender women who
      have sex with men to receive a combination of two oral antiretroviral drugs,
      emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily.
      All subjects received HIV testing, risk-reduction counseling, condoms, and
      management of sexually transmitted infections. RESULTS: The study subjects were
      followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these
      subjects, 10 were found to have been infected with HIV at enrollment, and 100
      became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo
      group), indicating a 44% reduction in the incidence of HIV (95% confidence
      interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected
      in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects
      (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in
      the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar
      rates of serious adverse events (P=0.57). CONCLUSIONS: Oral FTC-TDF provided
      protection against the acquisition of HIV infection among the subjects.
      Detectable blood levels strongly correlated with the prophylactic effect. (Funded
      by the National Institutes of Health and the Bill and Melinda Gates Foundation;
      ClinicalTrials.gov number, NCT00458393.).

PMID- 21091296
TI  - Isoflavone phytoestrogens in soymilk fermented with beta-glucosidase producing
      probiotic lactic acid bacteria.
AB  - Isoflavones significantly contribute to human health and disease prevention, and
      exist as glucosides and aglycones. The beta-glucosidase enzyme that hydrolyzes
      glucosides to aglycones is very sensitive to molecular structure, and thus the
      profile of the isoflavones can affect their rate of hydrolysis. Soymilk was
      fermented with Lactobacillus acidophilus B4496 (La), Lactobacillus bulgaricus
      CFR2028 (Lb), Lactobacillus casei B1922 (Lc), Lactobacillus plantarum B4495 (Lp)
      and Lactobacillus fermentum B4655 (Lf) for 48 h at 37 degrees C. beta-Glucosidase
      activity was determined using p-nitrophenyl beta-D-glucopyranoside as a substrate
      and the hydrolysis was carried out in soymilk. During fermentation, maximum
      growth was seen at 24 h with Lb, Lc, Lp and Lf and at 48 h with La. Polyphenol
      content ranged from 12.98 to 17.90 at 24 h and from 12.44 to 15.24 mg/100 ml at
      48 h of fermentation. All the lactic acid bacteria produced beta-glucosidase
      enzyme, which hydrolyzed isoflavone glucosides to aglycones at a significant
      level (P < 0.05) in the fermented soymilk.

PMID- 21091297
TI  - Tanreqing injection combined with conventional Western medicine for acute
      exacerbations of chronic obstructive pulmonary disease: a systematic review.
AB  - OBJECTIVE: In China, most patients with acute exacerbations of chronic
      obstructive pulmonary disease (COPD) are usually treated with Tanreqing injection
      plus conventional Western medicine. However, the value of its use remains
      uncertain. The objective of this systematic review is to compare the efficacy of
      Tanreqing injection plus conventional Western medicine with that of conventional
      Western medicine alone (therapy A versus therapy B, respectively) in the
      management of acute exacerbations of COPD. METHODS: Literature retrieval was
      conducted using the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE,((r)) EMBASE, Chinese Biomedical Database (CBM), and other electronically
      available databases from respective inception to August 2009. In addition, manual
      search of some traditional Chinese journals was performed to identify potential
      studies. Review authors independently extracted the trial data and assessed the
      quality of each trial. The following outcomes were evaluated: (1) forced
      expiratory volume in 1 second as a percentage of the predicted value; (2)
      arterial partial pressure of oxygen (Po(2)); (3) arterial partial pressure of
      carbon dioxide (Pco(2)); (4) length of hospital stay; (5) marked efficacy rate;
      (6) interleukin-8; and (7) adverse events. RESULTS: Based on the search strategy,
      14 trials involving 954 patients were finally included. Our results showed that
      compared with therapy B, therapy A improved Po(2), clinical efficacy, and lung
      function, reduced Pco(2), shortened the length of hospital stay, and was thus
      more therapeutically beneficial. No serious adverse events were reported.
      CONCLUSIONS: Within the limitations of this systematic review, we can conclude
      that compared with therapy B, therapy A may provide more benefits for patients
      with acute exacerbations of COPD. Further large-scale high-quality trials are
      warranted.

PMID- 21091299
TI  - Staying on the cutting edge.

PMID- 21091301
TI  - An activity systemic approach to augmentative and alternative communication.
AB  - The purpose of this paper is to discuss and highlight how Cultural-Historical
      Activity Theory (CHAT) can contribute to the understanding of the different
      factors at play when a person is using augmentative and alternative communication
      (AAC). It is based on data from a 3-year project concerning activity-based
      vocabulary design of voice output communication aids (VOCAs). Four persons who
      used AAC and their assistants were interviewed about shopping activities and
      their views about a vocabulary that included pre-stored phrases. A CHAT model,
      the Activity Diamond, was applied in an analysis of the data. The result was a
      multiplicity of human, artifactual, and natural factors, in which six themes were
      identified: Attitude/Preference, Expectation/Trust, Goal/Power, Place/Space,
      Time/Learning, and Usability/Accessibility. The themes are exemplified and
      discussed in relation to AAC.

PMID- 21091298
TI  - Bacterial species present in the lower male genital tract: a five-year
      retrospective study.
AB  - OBJECTIVES: To identify bacterial species present in the lower genital tract of
      males and to investigate the relationship with semen quality. METHODS: The
      microscopic analyses and cultures of 696 semen specimens, collected over five
      years from males investigated for subfertility, were retrospectively assessed.
      RESULTS: Semen cultures were sterile in 48%; they showed a polymicrobial flora
      (more than two bacterial species) in 30%, and were positive (>1 * 10(3) colony
      forming units/ml) in 22% of the cases. Gardnerella vaginalis was the most
      frequently isolated bacterium, followed by Escherichia coli and Enterococcus sp.
      Ureaplasma urealyticum was recovered from 13 of 147 samples (9%). Of patients
      with bacteriospermia 42% had leukospermia (>10(6) leukocytes/ml of semen).
      Bacteriospermia and leukospermia did not correlate with each other although a
      positive correlation was found between the presence of leukocytes and G.
      vaginalis isolation. Semen parameters were correlated with the bacterial species
      isolated most frequently. In comparison with controls, sperm concentration,
      motility and morphology were mostly deteriorated in the presence of G. vaginalis
      and U. urealyticum. CONCLUSIONS: Positive seminal fluid cultures must be
      interpreted with caution, taking into account both raised colony counts of single
      isolates and leukocyte concentration in the semen. Thus the common misdiagnosis
      of genital tract infection, based on the presence of seminal bacteria, and
      unnecessary treatment with antibiotics may be avoided.

PMID- 21091302
TI  - A qualitative analysis of email interactions of children who use augmentative and
      alternative communication.
AB  - The aim of this study was to introduce email as a form of interaction for a group
      of six children who used augmentative and alternative communication. In a 12-week
      exploratory study, aspects of the email messages sent were analyzed. The content
      of the messages was analyzed by an inductive qualitative method, and seven
      descriptive categories emerged. The most frequently occurring categories were
      Social Etiquette, Personal/Family Statistics and Personal Common Ground. The
      children utilized different email strategies that included use of most of the
      above-mentioned categories. Through the email writing practice, the children
      developed new social skills and increased their social participation. Email
      practice may be a good strategy to increase children's social networks.

PMID- 21091303
TI  - Evaluation of a speech recognition prototype for speakers with moderate and
      severe dysarthria: a preliminary report.
AB  - This study described preliminary work with the Supplemented Speech Recognition
      (SSR) system for speakers with dysarthria. SSR incorporated automatic speech
      recognition optimized for dysarthric speech, alphabet supplementation, and word
      prediction. Participants included seven individuals with a range of dysarthria
      severity. Keystroke savings using SSR averaged 68.2% for typical sentences and
      67.5% for atypical phrases. This was significantly different to using word
      prediction alone. The SSR correctly identified an average of 80.7% of target
      stimulus words for typical sentences and 82.8% for atypical phrases. Statistical
      significance could not be claimed for the relations between sentence
      intelligibility and keystroke savings or sentence intelligibility and system
      performance. The results suggest that individuals with dysarthria using SSR could
      achieve comparable keystroke savings regardless of speech severity.

PMID- 21091304
TI  - Strategies in construction and interpretation of graphic-symbol sequences by
      individuals who use AAC systems.
AB  - Given the frequent use of graphic symbols in augmentative and alternative
      communication (AAC) systems, some individuals who use AAC may have greater
      familiarity with constructing graphic-symbol sequences than do speaking
      individuals without disabilities. Whether this increased familiarity has an
      impact on the interpretation of such sequences or on the relationship between
      construction and interpretation is fundamental to our understanding of the
      mechanisms underlying communication using graphic symbols. In this study,
      individuals who use graphic-symbol AAC systems were asked to construct and
      interpret graphic-symbol sequences representing the same target content (simple
      and complex propositions). The majority of participants used stable response
      patterns on both tasks; a minority were inconsistent on both tasks. Asymmetrical
      patterns (stable on one task but not the other) were rare, suggesting that
      neither channel (construction or interpretation) preceded the other, in contrast
      to earlier findings with participants without disabilities (i.e., novice users of
      graphic symbols). Furthermore, there were differences between stable and less
      stable responders on measures of syntactic comprehension and cognitive level but
      not on chronological age, receptive vocabulary, or AAC system characteristics and
      length of use.

PMID- 21091305
TI  - Engineering injectable bone using bone marrow stromal cell aggregates.
AB  - With the increasing popularity of minimally invasive surgery, to develop an
      injectable bone would be highly preferable for the repair of bone nonunions and
      defects. However, the use of dissociated cells and exogenous carriers to
      construct injectable bone faces several drawbacks. To circumvent these
      limitations, we first harvested a cell sheet from rabbit bone marrow stromal
      cells using a continuous culture method and a scraping technique. The obtained
      sheet was then cut into fragments of multicellular aggregates, each of which was
      composed of a certain number of cells, extracellular matrix, and intercellular
      connections. The aggregates showed apparent mineralization properties, high
      alkaline phosphatase activity, increased osteocalcin content, and upregulated
      bone markers, implying their in vitro osteogenic potential. Then, serum-free
      medium (the control group), dissociated cell suspension (the cell group), and
      suspension of multicellular aggregates (the aggregate group) were injected
      subcutaneously on the back of the nude mice to evaluate ectopic bone formation.
      The results revealed that the aggregate group showed significantly larger and
      denser bone at the injection sites than the cell group, whereas bone formation
      did not occur in the control group. Additionally, when injecting them locally
      into the mandibular fracture gap of delayed healing in a rabbit model, we
      observed the most improved bone healing in the aggregate group. More cells
      survive and retain at the injection sites in the aggregate group than that in the
      cell group postoperatively. Our study indicates that the multicellular aggregates
      might be considered a promising strategy to generate injectable bone tissue and
      improve the efficacy of cell therapy.

PMID- 21091306
TI  - Antiepileptic drugs and suicide risk: could stopping medications pose a greater
      hazard?

PMID- 21091307
TI  - Should older patients be denied temporal lobectomy on the basis of age?

PMID- 21091308
TI  - Transcranial magnetic stimulation and the treatment of suicidality.

PMID- 21091310
TI  - Alemtuzumab in the treatment of relapsing-remitting multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disorder characterized by CNS
      inflammation, demyelination and cellular damage with atrophy. Most patients with
      MS initially present with a relapsing-remitting course, with periodic episodes of
      neurologic symptomatology that do not follow a predictable pattern. In order to
      maintain a stable clinical course, it is felt to be important to control the
      number and severity of relapses, as disability, at least in part, is a cumulative
      effect of damage from multiple lesions within the brain and spinal cord.
      Historically, MS has not been considered curable, because the immune system could
      not be adequately normalized over the course of a lifetime. Alemtuzumab (Campath
      1H; Campath((r)), Genzyme, MA, USA) has recently been investigated in a Phase II
      clinical trial in the treatment of relapsing-remitting MS. The results observed
      in the study are very encouraging and multiple insights have been made into the
      nature of autoimmunity in general based on the clinical response to this
      monoclonal antibody. Enrollment in two pivotal Phase III clinical trials of
      alemtuzumab in MS is now complete.

PMID- 21091311
TI  - The protective role of brain size in Alzheimer's disease.
AB  - The brain reserve hypothesis suggests that larger brain size is associated with a
      greater ability to tolerate pathological damage before showing any cognitive
      decline. This theory has been used to explain why many patients with Alzheimer's
      disease pathology are cognitively normal before death. However, the literature
      concerning the brain reserve hypothesis is mixed with evidence both for and
      against this theory. Perneczky and colleagues tested the theory by assessing
      whether premorbid brain size, measured using head circumference, alters the
      relationship between brain atrophy and cognitive decline in 270 Alzheimer's
      disease patients. They found that head circumference was associated with a
      reduced impact of atrophy on cognitive performance. Hence, for a given degree of
      atrophy, cognitive performance was better in patients with a larger head
      circumference. Therefore, these findings support the brain reserve hypothesis.
      This article will discuss the brain reserve concept and potential limitations and
      significance of this study.

PMID- 21091312
TI  - Psychogenic nonepileptic seizures: diagnosis and initial management.
AB  - Psychogenic nonepileptic seizures (PNES; also known as pseudoseizures,
      nonepileptic attack disorder) are common. They continue to pose diagnostic
      difficulties, with mean delays from onset to diagnosis of several years, during
      which time they are often treated as epilepsy. The literature suggests that
      clinical diagnosis has limited reliability. However, it may be useful to regard
      the diagnosis of PNES as having two stages-- that of suspecting the diagnosis and
      that of confirming it. Clinical features of the history and spells allow the
      diagnosis of PNES to be suspected in the first place, so that the appropriate
      expertise and tests can be brought to bear. The diagnosis of PNES is usually
      confirmed by recording spells using video EEG. A minority of patients also have
      epilepsy. Once the diagnosis is made, initial management consists of
      communicating the diagnosis to the patient and carers in a clear and
      nonpejorative way, as well as withdrawing anticonvulsant medication with
      appropriate monitoring in patients with no evidence of epilepsy. In many
      patients, spells will cease without psychological intervention. Emergency
      healthcare utilization may drop sharply after explanation of the diagnosis, and
      this may occur even in patients whose spells continue. It is not clear to what
      degree these positive effects are maintained in the long term.

PMID- 21091313
TI  - Development of Parkinson's disease biomarkers.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder,
      affecting over 6 million people worldwide. It is anticipated that the number of
      affected individuals may increase significantly in the most populous nations by
      2030. During the past 20 years, much progress has been made in identifying and
      assessing various potential clinical, biochemical, imaging and genetic biomarkers
      for PD. Despite the wealth of information, development of a validated biomarker
      for PD is still ongoing. It is hoped that reliable and well-validated biomarkers
      will provide critical clues to assist in the diagnosis and management of
      Parkinson's disease patients in the near future.

PMID- 21091314
TI  - Imaging cognitive and behavioral symptoms in Parkinson's disease.
AB  - Non-motor symptoms are a major and often unrecognized cause of morbidity of
      Parkinson's disease. In the past few years, imaging technology, such as
      functional MRI and PET, have provided a large bulk of information about the
      phenomena. Here, we provide an overview of those imaging studies that may help us
      understand the neuronal correlates associated with non-motor symptoms in
      Parkinson's disease, with a particular focus on cognitive and neuropsychiatric
      deficits.

PMID- 21091315
TI  - Gene therapy for Parkinson's disease: where are we now and where are we going?
AB  - The number of patients worldwide who have received some kind of gene therapy is
      now in the thousands. A subset of that number have received intracranial
      injections of adeno-associated viruses encoding various therapeutic genes
      directed at ameliorating Parkinson's disease (PD). In this article we briefly
      examine the current status of Phase I and Phase II trials of gene therapy for PD
      and preview some of the improvements in delivery technology that promise to make
      adeno-associated-virus-based gene therapy for PD safer and more accessible to
      interventional neurologists around the world.

PMID- 21091316
TI  - Animal models for autosomal dominant frontal lobe epilepsy: on the origin of
      seizures.
AB  - Autosomal dominant frontal lobe epilepsy (ADNFLE) can be caused by mutations in
      either the alpha4 or beta2 subunit of the neuronal nicotinic Ach receptor. In
      vitro expression studies in Xenopus oocytes or human embryonic kidney cells have
      been proven to be valuable tools for the characterization of these mutations, but
      they do not fully resemble the situation in vivo. Compared with them, animal
      models have the advantage that the functional consequences of a given mutation
      can be studied in the complex context of an intact living organism. Recent
      transgenic and knock-in animal models and their valuable contributions to our
      current understanding of ADNFLE epileptogenesis are discussed in this article.
      Several of the mouse and rat models support the hypothesis that ADNFLE mutations
      cause seizures mainly by increasing GABAergic inhibition, and a conditional knock
      in mouse model adds early embryonal structural changes as another possible
      pathogenetic mechanism.

PMID- 21091317
TI  - Electroencephalographic assessment of patients with epileptic seizures.
AB  - This article reviews the role of EEG in the diagnosis and management of patients
      with epilepsies. We review the morphologic and behavioral characteristics of the
      interictal and ictal EEG markers of the different types of epilepsy that should
      guide recording strategies to augment its diagnostic yield, and we attempt to
      delineate those particular features that may be relevant to the main epilepsy
      syndromes. Particular emphasis is placed on the activation methods, including
      hyperventilation, sleep deprivation and sleep, and specific triggers, as well as
      how these may differ between idiopathic and cryptogenic/symptomatic generalized
      and focal epilepsies, commenting on possible diagnostic pitfalls and areas of
      uncertainty. We also consider the indications for long-term recordings (video-
      telemetry and ambulatory) and emphasize the diagnostic value of polygraphic
      recordings.

PMID- 21091318
TI  - Generic substitution of antiepileptic drugs.
AB  - Substitution of antiepileptic drugs with generic formulations may affect
      individual people, as well as healthcare systems. Analyses of large medical
      claims databases suggest that generic substitution of antiepileptic drugs is
      associated with increased morbidity and greater use of healthcare resources.
      While a single brand-to-generic switch may be associated with a slight increase
      in overall medical costs, multiple switches may be associated with higher costs,
      perhaps because different generic agents are not required to be bioequivalent to
      each other. Generic substitution also affects the individual: along with the
      possible increased risk of seizures or adverse events, inconsistency of supply
      may make the medication appear unfamiliar, thus discouraging adherence.
      Importantly, substitution is often carried out at the dispensing level, without
      the knowledge or consent of physicians and affected individuals. Therefore,
      regulatory and professional bodies advocate that substitution should not be
      carried out without specific counseling of the individual by healthcare
      professionals on the details and implications of the change.

PMID- 21091320
TI  - Short communication: persistence of high blood levels of the chemokines CCL2,
      CCL19, and CCL20 during the course of HIV infection.
AB  - Dendritic cells (DCs) are important mediators of the immune response against HIV
      and yet blood DC numbers fall substantially during HIV infection. Here we report
      that blood levels of the DC-tissue tropic chemokines monocyte chemotactic protein
      (MCP-1/CCL2), macrophage inflammatory proteins (MIP-3alpha/CCL20), and MIP
      3beta/CCL19 remained elevated throughout the course of HIV infection suggesting
      that the relatively low levels of blood circulating DCs may be due to active
      recruitment of these cells to peripheral sites to fight disease progression.

PMID- 21091321
TI  - Pharmacokinetics of the prodrug thiamphenicol glycinate and its active parent
      compound thiamphenicol in beagle dogs following intravenous administration.
AB  - 1. This study investigated the pharmacokinetics of thiamphenicol glycinate (TG)
      and thiamphenicol (TAP) in beagles (n = 6) after intravenous administration of 50
      mg/kg TG hydrochloride. Plasma concentrations of TG and TAP were measured by a
      HPLC-UV method. 2. Two-compartment model was selected to describe the
      pharmacokinetic characteristics of TG and TAP in vivo. Main parameters were as
      follows: AUC(0-infinity) of TAP and TG were 16,328 +/- 1682 ug.min/mL and 3943 +/
      546 ug.min/mL, respectively. The total plasma clearance (CL) of TG and TAP were
      12.7 +/- 2.0 mL/min/kg and 2.5 +/- 0.3 mL/min/kg, respectively. Mean residence
      time (MRT) of TG and TAP were 27.5 +/- 3.5 and 207.2 +/- 20.2 min, respectively.
      The transformative rate constant (k(1M)) from TG to TAP was 0.0477 +/- 0.0028
      min(-1). The elimination rate constant (k(M10)) from TAP was 0.0238 +/- 0.0044
      min(-1). Coefficients of variation (CV) between observed values and predicted
      ones were 5.9% and 18.2%, respectively. The volume of distribution of the central
      compartment for TG (V(C)) and TAP (V(CM)) were 0.264 +/- 0.022 L/kg and 0.127 +/-
      0.023 L/kg, respectively. 3. Pharmacokinetic parameters suggested that TG was
      presumably cleaved quickly by tissue esterase to release TAP for effectiveness in
      beagles after administration.

PMID- 21091323
TI  - Characteristics of high-molecular-weight hyaluronic acid as a brain-derived
      neurotrophic factor scaffold in periodontal tissue regeneration.
AB  - Brain-derived neurotrophic factor (BDNF), for which bovine collagen-derived
      atelocollagen is used as a scaffold, enhances periodontal tissue regeneration.
      However, a scaffold that does not contain unknown ingredients is preferable.
      Since the synthesized high-molecular-weight (HMW)-hyaluronic acid (HA) is safe
      and inexpensive, we evaluated the efficacy of HMW-HA as a BDNF scaffold. CD44, a
      major receptor of HA, was expressed in cultures of human periodontal ligament
      cells, and HMW-HA promoted the adhesion and proliferation of human periodontal
      ligament cells, although it did not influence the mRNA expression of bone
      (cementum)-related proteins. The in vitro release kinetics of BDNF from HMW-HA
      showed that BDNF release was sustained for 14 days. Subsequently, we examined the
      effect of BDNF/HMW-HA complex on periodontal tissue regeneration in dogs. A
      greater volume of newly formed alveolar bone and a longer newly formed cementum
      were observed in the BDNF/HMW-HA group than in the HMW-HA group, suggesting that
      HMW-HA assists the regenerative capacity of BDNF, although HMW-HA itself does not
      enhance periodontal tissue regeneration. Neither the poly (lactic-co-glycolic
      acid) group nor the BDNF/poly (lactic-co-glycolic acid) group enhanced
      periodontal tissue regeneration. In conclusion, HMW-HA is an adequate scaffold
      for the clinical application of BDNF.

PMID- 21091324
TI  - Effects of 1 GeV/nucleon (56)Fe Particles on Longevity, Carcinogenesis and
      Neuromotor Ability in Atm-Deficient Mice.
AB  - Abstract As therapeutic uses of high-LET radiation become more prevalent and
      human space exploration continues to be a focus of NASA, it is important to
      understand the biological effects of high-LET radiation and the role of genetics
      in sensitivity to high-LET radiation. To study genetic susceptibility to
      radiation, we used mice deficient in Atm activity (AtmDeltaSRI). ATM is important
      in DNA repair, apoptosis and cell cycle regulation. Although homozygous mutations
      in ATM are rare, the prevalence of ATM heterozygosity is estimated to be 1% and
      results in an increased cancer risk. We found that the effects of 1 Gy 1
      GeV/nucleon (56)Fe particles on life span and tumorigenesis are genotype- and sex
      specific. Significant effects of 1 Gy 1 GeV/nucleon (56)Fe particles on incidence
      of non-cancer end points were seen; however, 2 Gy 1 GeV/nucleon (56)Fe particles
      significantly affected neuromotor ability. Our results represent an extensive
      investigation into the late effects of high-LET radiation exposure in a sex- and
      genotype-dependent manner and provide a baseline for understanding the long-term
      risks of high-LET radiation.

PMID- 21091322
TI  - Mechanisms of gender-specific regulation of mouse sulfotransferases (Sults).
AB  - 1. Marked gender differences in the expression of sulfotransferases (Sults) are
      known to exist in several species including rats, mice and hamsters. However, the
      mechanism for this gender difference is not known. Therefore, in the present
      study, it was determined whether sex and/or growth hormone (GH) are responsible
      for the gender difference in the expression of Sults using gonadectomized (GNX),
      hypophysectomized (HX) and GH-releasing hormone receptor-deficient little
      (lit/lit) mouse models. 2. Sult1a1 and Papss2 in liver and kidney, and Sult1d1 in
      liver are female-predominant in mice because of suppressive effects of both
      androgens and male-pattern GH secretion. Sult2a1/a2 is the most markedly female
      predominant Sult in mouse liver due to suppressive effects of androgens and male
      pattern GH secretion, as well as stimulatory effects by estrogens and female
      pattern GH secretion. Sult3a1 is female-predominant in mouse liver due to
      suppressive effects of androgens as well as stimulatory effects of estrogens and
      female-pattern GH secretion. Sult1c1 expression is male-predominant in mouse
      liver and kidney because of stimulatory effects of androgens in males. Sult4a1
      expression is female-predominant in mouse brain due to stimulatory effects of
      estrogens. 3. In conclusion, gender-divergent Sults are mostly female-predominant
      and Sult1c1 is the only male-dominant Sult. The gender differences in expression
      of various mouse Sults are influenced by various mechanisms involving sex and/or
      GHs.

PMID- 21091326
TI  - Probing the osteoinductive effect of calcium phosphate by using an in vitro
      biomimetic model.
AB  - The use of calcium phosphate (CaP)-based carriers in bone engineering is a
      promising approach to induce in vivo bone formation. However, the exact mechanism
      of osteoinduction by CaP is not known. Here, by mimicking the in vivo Ca(2+) and
      P(i)-enriched environment in an in vitro model, we assessed the effects of these
      ions on human periosteum-derived cells. We observed a significant Ca(2+) and P(i)
      induced cell proliferation, which was found to be through the modulation of cell
      cycle progression, in a dose- and time-dependent manner. In addition, Ca(2+),
      P(i), and combined Ca-P upregulated osteogenic gene expression in a dose- and
      time-dependent manner. Encouragingly, both ions administered individually or in
      combination persistently and dose dependently upregulated bone morphogenetic
      protein-2 gene expression. This suggested a potential osteoinductive effect
      through an autonomous activation of the bone morphogenetic protein signaling
      pathway by released Ca(2+) and P(i), which may serve as an autocrine/paracrine
      osteoinduction loop that drives the cellularized CaP constructs toward effective
      bone formation in vivo. In conclusion, through an in vitro biomimetic model, we
      have partially probed the roles of the released Ca(2+) and P(i) on the
      osteoinductivity of CaP-based biomaterials.

PMID- 21091327
TI  - Enhanced proliferation and chondrogenic differentiation of human synovium-derived
      stem cells expanded with basic fibroblast growth factor.
AB  - Synovium-derived stem cell (SDSC) is one of valuable sources for cartilage
      regeneration. Basic fibroblast growth factor (bFGF) was reported to augment the
      differentiation potential of mesenchymal stem cells originating from a variety of
      sources. In this study, we applied various concentrations of bFGF to monolayer
      cultures of SDSCs and evaluated its effects on proliferation and chondrogenesis.
      SDSCs expressed mRNAs of FGF receptor 1, 2, 3, and 4, but produced only FGF
      receptor 3 protein. The SDSCs were expanded as monolayer supplemented with
      various concentrations of bFGF (0, 0.1, 1, 10, and 100 ng/mL) before
      chondrogenesis. Cell shrinkage and increased actin expression was noted as well
      as enhanced proliferation by bFGF treatment in monolayer cultures. Cell surface
      marker CD34 and CD49a expression of SDSCs was decreased with 10 and 100 ng/mL of
      bFGF. In micromass pellet cultures, bFGF-treated SDSCs showed augmented sizes,
      weights, and glycosaminoglycan accumulation of pellets by bFGF supplementation.
      Messenger RNA and protein expression of type II and type X collagen were
      upregulated in pellets cultured bFGF. These results demonstrated that bFGF was an
      effective agent for the enhancement of SDSC proliferation and chondrogenesis.
      From the results in this study, we could elect the 10 ng/mL of bFGF as an optimal
      concentration for pretreatment of SDSCs before chondrogenic differentiation.

PMID- 21091328
TI  - Emergency medical services: a journey to subspecialty.

PMID- 21091329
TI  - Ondansetron is safe and effective for prehospital treatment of nausea and
      vomiting by paramedics.
AB  - OBJCTIVE: The objectives were to evaluate the safety and efficacy of ondansetron
      in the out-of-hospital treatment of undifferentiated nausea or vomiting. METHODS:
      Patients with severe nausea or intractable vomiting who were transported by
      paramedic-staffed ambulances in eight California counties were treated with
      intravenous (IV), intramuscular (IM), or oral dissolving tablet (ODT)
      administration of ondansetron. Data were collected prospectively for a six-month
      period using an online database. Prospectively defined outcome measures were 1)
      efficacy as measured by a quantitative visual analog nausea scale and 2)
      incidence of adverse effects. There were no control or placebo groups. RESULTS:
      Data was collected for 2072 patients, but one patient did not receive the
      medication. Therefore, Ondansetron was administered to 2,071 patients (3.7% of
      transported patients). Most patients were adult, with only 66 patients less than
      18 years old. Of the 2,071 patients, 1,320 (64%) received IV administration, 77
      (4%) received IM administration, and 674 (33%) received ODT administration of
      ondansetron. Intravenous administration resulted in the largest improvements in
      nausea scores (mean 4.4; 95% confidence interval [CI] 4.2, 4.5), followed by IM
      (mean 3.6; 95% CI 3.0, 4.3) and ODT (mean 3.3; 95% CI 3.1, 3.5). Overall, the
      mean decrease in nausea score was 4.0 (95% CI 3.9, 4.1; p < 0.001) on a 10-point
      scale. After medication administration, four patients had mild hypotension, one
      had hypertension, two had itching or rash, and one had a brief episode of
      supraventricular tachycardia that resolved spontaneously. CONCLUSIONS:
      Ondansetron is safe and effective for out-of-hospital treatment of nausea and
      vomiting when administered by paramedics via the IV, IM, or oral route. When
      available to paramedics, ondansetron is used frequently.

PMID- 21091330
TI  - A new defibrillator mode to reduce chest compression interruptions for health
      care professionals and lay rescuers: a pilot study in manikins.
AB  - BACKGROUND: Chest compression interruptions are detrimental during the
      resuscitation of cardiac arrest patients, especially immediately prior to shock
      delivery. OBJECTIVE: To evaluate the effect of use of a new defibrillator
      technology, which filters compression-induced artifact and provides reliable
      rhythm analysis with automatic defibrillator charging during chest compressions,
      on preshock chest compression interruption. METHODS: Thirty subjects (20 basic
      life support [BLS]; 10 advanced life support [ALS]) worked in pairs to perform
      two randomly ordered simulated cardiac resuscitations with the defibrillator
      operating in either standard mode (ALS = manual; BLS = automated external
      defibrillator [AED]) or the new Analysis and Charging during CPR (AC-CPR) mode.
      During each resuscitation simulation, rescuers switched roles as chest compressor
      and defibrillator operator every two segments of CPR (one segment = 2 minutes of
      chest compressions, rhythm analysis, and shock delivery, if appropriate), for
      eight total segments. The participants rested >=30 minutes between trials and
      received brief AC-CPR training (BLS = 30 seconds; ALS = 5 minutes). Heart rate
      and perceived exertion were measured with pulse oximetry and the Borg scale,
      respectively. RESULTS: Mean (+/- standard deviation) preshock chest compression
      pause time was considerably shorter in each CPR segment with AC-CPR versus
      standard defibrillator operation (2.13 +/- 0.99 sec vs. 10.93 +/- 1.33, p <
      0.0001), demonstrating effective use of AC-CPR with minimal training. Despite
      reduced chest compression interruption with AC-CPR, rescuer fatigue and perceived
      exertion did not differ in any CPR segment with standard defibrillator operation
      versus AC-CPR (p = 0.2-1.0). CONCLUSIONS: Preshock pause time is reduced by 80%
      utilizing a novel technology that employs automated analysis and charging during
      chest compression. Although chest compression pause time is reduced with the use
      of the new technology, participants do not excessively fatigue.

PMID- 21091332
TI  - Neuroendocrine tumor (carcinoid) metastatic to orbital extraocular muscle: case
      report and literature review.
AB  - PURPOSE: To report a patient who showed neuroendocrine tumor (carcinoid)
      metastasis to the medial rectus muscle and to review patients' characteristics of
      carcinoid metastases to the extraocular muscles. CASE: A 72-year-old woman, who
      initially presented with spindle-shaped enlargement of the right medial rectus
      muscle, was followed for 3 years with a diagnosis of orbital myositis. Initial
      biopsy of the medial rectus muscle showed inflammation only. She showed remission
      and exacerbation of right proptosis and eyelid swelling, which responded to oral
      and intravenous steroids. On the occasion of abdominal computed tomography for
      ischemic colitis, a large retroperitoneal mass was detected and diagnosed as well
      differentiated neuroendocrine tumor. The gradual increase of the medial rectus
      muscle with optic nerve compression, and hence, visual reduction, prompted a
      second excisional biopsy of the medial rectus mass, which proved to be
      neuroendocrine tumor metastasis. Whole body 2-[(18)F]fluoro-2-deoxy-D-glucose
      (FDG) positron emission tomography fused with computed tomography revealed
      abnormal uptake only in the right orbit (maximum standardized uptake value:
      SUVmax = 3.83), and the patient underwent radiation to the right orbit with the
      subsidence of the residual mass. RESULTS: The literature review found 15
      patients, including this patient, with neuroendocrine tumor metastases to the
      extraocular muscles. Frequent symptoms and signs were diplopia, proptosis, and
      ocular motility limitation. CONCLUSIONS: Neuroendocrine tumor appears to have
      propensity to extraocular muscle metastases and its slow growth might pose
      difficulty in differential diagnoses of orbital myositis.

PMID- 21091333
TI  - Large-angle strabismus: can a single surgical procedure achieve a successful
      outcome?
AB  - PURPOSE: Large-angle strabismus is a gray zone for surgeons with various
      advocates for one, two-, three-, or even four-muscle surgeries. Very frequently,
      reoperations are required in these cases in order to achieve a successful
      outcome. In this article, the authors evaluate the outcome of concomitant large
      angle strabismus after a single surgical procedure. METHODS: A retrospective
      analysis of all operated cases of concomitant large-angle strabismus (50 prism
      diopters or more) during a 1.5-year period was performed from patient's case
      files. A successful outcome of surgery was defined as deviation within 10 prism
      diopters of orthophoria/tropia for both distance and near. RESULTS: Fifty
      patients met the inclusion criteria. The overall success rate was 60%, with the
      esotropia group having a higher success rate (68.75%) than the exotropia group
      (44.45%). Ten patients underwent recess-resect procedure, 20 had bimedial rectus
      recession, and 3 had bilateral lateral rectus recession, while 17 patients had
      surgery on 3 horizontal rectus muscles. Thirty-three patients had two-muscle
      surgery with a success rate of 57.58%, while 17 patients had three-muscle surgery
      with a success rate of 64.71%, the difference being statistically insignificant.
      There was no statistically significant difference between the various age groups
      analyzed for overall success rate, suggesting that age group is not a factor for
      positive outcome in large-angle strabismus surgery. A total of 12 patients were
      amblyopic at the time of strabismus surgery and they had a success rate of
      33.33%, which was much poorer than the success rate (68.42%) of the remaining 38
      patients who did not have amblyopia at the time of surgery. CONCLUSIONS: A good
      surgical outcome can be obtained in large-angle strabismus with a single surgical
      procedure, though a randomized controlled study needs to be done to establish
      whether three-muscle surgeries give better results than two-muscle surgeries.

PMID- 21091334
TI  - Bupivacaine injection to treat exotropia and esotropia.
AB  - PURPOSE: To report the results of bupivacaine injection into the extraocular
      muscles to treat horizontal strabismus, both exotropia and esotropia. METHODS:
      Bupivacaine, 4.5 ml of a 0.50% solution, was injected into the medial rectus
      muscle in each of 14 exotropic patients and into the lateral rectus muscle in
      each of 6 esotropic patients with electromyographic control. The measures of
      alignment were made before the procedure and 1, 3, 6, and 12 months after
      injection. RESULTS: Of 20 patients, 15 had improved ocular alignment with the
      average change of 8.46, 8.2, 8.33 and 9 prism diopters (PD) at 1,3, 6 and 12
      months, respectively. Two of 5 (40%) incomitant strabismus patients and 13 of 15
      (86.66%) comitant strabismus patients had improvement in ocular alignment. Eleven
      of 14 exotropic patient and 4 of 6 esotropic patients had improvement in ocular
      alignment, averaging 9.73, 9.36, 9.54 and 6 PD in the exotropic group and 5, 5,
      5, and 10.5 PD in the esotropic group. There was no serious complication from the
      injections. CONCLUSIONS: Bupivacaine injection improved ocular alignment in some
      patients. Denervated extraocular muscle did not respond well to bupivacaine.
      Bupivacaine improved ocular alignment equally in esotropic and exotropic
      patients.

PMID- 21091335
TI  - Ophthalmic assessment of children with down syndrome: is England doing its bit?
AB  - INTRODUCTION: Patients with Down syndrome have characteristic features including
      ocular manifestations. Guidelines exist for ophthalmic surveillance of people
      with Down syndrome, but locally (North Staffordshire) there is no formal program
      in place. METHODS: Hospital records were used to detect children with Down
      syndrome. Data were extracted retrospectively to determine which children had
      been seen by ophthalmic services, the mode of assessment used, and the frequency
      of ophthalmic disorders. RESULTS: Of the 96 children with Down syndrome, 38%
      received no ophthalmic assessment. Of those seen, the mean age at first
      appointment was nearly 3 years, with a number of children being more than 5 years
      old. Most children (96%) had at least one ophthalmic abnormality, the commonest
      being hyperopia. Requested follow-up was routinely exceeded by almost a year with
      19% of children receiving no follow-up. DISCUSSION: Ocular disorders are common
      in the two thirds of children who are currently seen by ophthalmic services.
      Locally, we are falling short of the targets set by the 2006 recommendations for
      basic medical care of people with Down syndrome. A screening program might have a
      beneficial impact on the vision of children with Down syndrome.

PMID- 21091336
TI  - How Dutch orthoptists deal with noncompliance with occlusion therapy for
      amblyopia.
AB  - BACKGROUND: We previously found that compliance with occlusion therapy for
      amblyopia is poor, especially among children of non-native parents who spoke
      Dutch poorly and who were low educated. We investigated conception, awareness,
      attitude, and actions to deal with noncompliance among Dutch orthoptists.
      METHODS: Orthoptists working in non-native, low socioeconomic status (SES) areas
      and a selection of orthoptists working elsewhere in the Netherlands were studied.
      They were observed in their practice, received a structured questionnaire, and
      underwent a semi-structured interview. Finally, a short survey was sent to all
      working orthoptists in the Netherlands. RESULTS: Nine orthoptists working in non
      native, low-SES areas and 23 working elsewhere in the Netherlands participated.
      One hundred and fifty-one orthoptists returned the short survey. Major
      discrepancies existed in conception, awareness, and attitude. Opinions differed
      on what should be defined as noncompliance and on what causes noncompliance. Some
      orthoptists found noncompliance annoying, unpleasant, and hard to imagine, others
      were more understanding. Many pitied the noncompliant child. Almost all thought
      that the success of occlusion therapy lies both with the parents and the
      orthoptist, but one third thought that noncompliance was not solely their
      responsibility. Patients' compliance was estimated at 69.3% in non-native, low
      SES areas (electronically, 52% had been measured), at 74.1% by the other 23
      orthoptists, and at 73.8% in the short survey. Actions to improve compliance were
      diverse; some increased occlusion hours whereas others decreased them. In non
      native, low-SES areas, 22% spoke Dutch moderately to none; the allotted time for
      a patient's first visit was 21'; the time spent on explaining to the parents was
      2'30" and to the child 10". In practices of the other 23 orthoptists, 6% spoke
      Dutch moderately to none (P<0.0001), the time for a patient's first visit was
      27'24" (P=0.47), and the periods spent explaining were 2'51" (P=0.59) and 26"
      (P=0.17), respectively. CONCLUSION: Conception, awareness, attitude, and actions
      to deal with noncompliance varied among orthoptists. In non-native, low-SES
      areas, time spent on explanation was shorter, despite a lower fluency in Dutch
      among the parents.

PMID- 21091337
TI  - About natural double vision. 1826.

PMID- 21091339
TI  - Implantation of autologous bone-marrow-derived cells reconstructs functional
      urethral sphincters in rabbits.
AB  - The purpose of this study was to determine if implantation of autologous bone
      marrow-derived cells has the potential to treat stress urinary incontinence
      caused by intrinsic sphincter deficiency. Bone marrow cells harvested from femurs
      of New Zealand White rabbits were cultured for 10 days. Seven days before
      implantation, the urethral sphincters located at the internal urethral orifice
      were cryo-injured by spraying liquid nitrogen for 15 s. The cultured autologous
      bone-marrow-derived cells were implanted 7 days after cryo-injury. For controls,
      cell-free solutions were injected. At 7 and 14 days after implantation, leak
      point pressures were determined and the urethral sphincters were examined by
      immunohistochemistry. At 7 and 14 days, the cell-implanted regions contained
      numerous striated and smooth muscle-like cells expressing myoglobin and smooth
      muscle actin, respectively. The proportions of myoglobin- and smooth muscle actin
      expressing areas in both the 7- and 14-day cell-implanted regions were
      significantly higher than in controls. By 14 days, these differentiated cells
      formed contacts with similar cells, creating layered muscle structures. At that
      time, the leak point pressure of the cell-implanted rabbits was significantly
      higher than that of the controls. In conclusion, autologous bone-marrow-derived
      cells can reconstruct functional urethral sphincters.

PMID- 21091338
TI  - Fibrocartilage tissue engineering: the role of the stress environment on cell
      morphology and matrix expression.
AB  - Although much is known about the effects of uniaxial mechanical loading on
      fibrocartilage development, the stress fields to which fibrocartilaginous regions
      are subjected to during development are mutiaxial. That fibrocartilage develops
      at tendon-to-bone attachments and in compressive regions of tendons is well
      established. However, the three-dimensional (3D) nature of the stresses needed
      for the development of fibrocartilage is not known. Here, we developed and
      applied an in vitro system to determine whether fibrocartilage can develop under
      a state of periodic hydrostatic tension in which only a single principal
      component of stress is compressive. This question is vital to efforts to
      mechanically guide morphogenesis and matrix expression in engineered tissue
      replacements. Mesenchymal stromal cells in a 3D culture were exposed to
      compressive and tensile stresses as a result of an external tensile hydrostatic
      stress field. The stress field was characterized through mechanical modeling.
      Tensile cyclic stresses promoted spindle-shaped cells, upregulation of scleraxis
      and type one collagen, and cell alignment with the direction of tension. Cells
      experiencing a single compressive stress component exhibited rounded cell
      morphology and random cell orientation. No difference in mRNA expression of the
      genes Sox9 and aggrecan was observed when comparing tensile and compressive
      regions unless the medium was supplemented with the chondrogenic factor
      transforming growth factor beta3. In that case, Sox9 was upregulated under static
      loading conditions and aggrecan was upregulated under cyclic loading conditions.
      In conclusion, the fibrous component of fibrocartilage could be generated using
      only mechanical cues, but generation of the cartilaginous component of
      fibrocartilage required biologic factors in addition to mechanical cues. These
      studies support the hypothesis that the 3D stress environment influences cell
      activity and gene expression in fibrocartilage development.

PMID- 21091341
TI  - The dynamic glycome microenvironment and stem cell differentiation into
      vasculature.
AB  - The ability to control stem cell differentiation is the holy grail of
      regenerative medicine. Although significant progress toward this goal has been
      achieved, few efficient and straightforward methods have been developed,
      necessitating a better understanding of the mechanisms that influence
      differentiation. The extracellular microenvironment is emerging as a major player
      in controlling stem cell fate. Cell surface and secreted heparan sulfate
      glycosaminoglycans (HSGAGs) are one element of the extracellular matrix that
      regulates complex cell signaling networks. HSGAGs facilitate binding and
      availability of cytokines to cells as they progress through development. For
      example, growth factors such as fibroblast growth factor and vascular endothelial
      growth factor bind to specific HSGAG sequences during vasculogenesis. HSGAGs have
      been shown to be critical for stem cell vasculogenesis as well as other
      differentiation lineages. Understanding the role that the extracellular
      microenvironment plays in controlling cell fate can lead us closer to directing
      differentiation for developmental models and regenerative therapies. This review
      will focus on the role of extracellular microenvironment in regulating cell
      differentiation, with particular attention to the role of HSGAGs in
      vasculogenesis.

PMID- 21091340
TI  - Osteogenic media and rhBMP-2-induced differentiation of umbilical cord
      mesenchymal stem cells encapsulated in alginate microbeads and integrated in an
      injectable calcium phosphate-chitosan fibrous scaffold.
AB  - The need for bone tissue engineering has increased as the world population ages.
      The objectives of this study were to (1) develop a novel human umbilical cord
      mesenchymal stem cell (hUCMSC)-encapsulating, fiber-reinforced injectable calcium
      phosphate cement (CPCF) scaffold, and (2) investigate the effects of osteogenic
      media delivery, preosteodifferentiation, and bone morphogenetic protein-2 (BMP-2)
      delivery on hUCMSC osteodifferentiation inside CPCF for the first time. CPCF was
      developed using calcium phosphate powders, chitosan, and absorbable fibers. Four
      types of hUCMSC-encapsulating constructs were fabricated: control media in
      alginate hydrogel microbeads in CPCF; osteogenic media in microbeads;
      preosteodifferentiation; and recombinant human BMP-2 (rhBMP-2) in microbeads. The
      hUCMSCs inside CPCF maintained good viability, successfully differentiated into
      the osteogenic lineage, and synthesized bone minerals. The
      preosteodifferentiation method yielded high gene expressions of alkaline
      phosphatase, osteocalcin, collagen, and osterix, as well as alkaline phosphatase
      protein synthesis. The mineralization for the preosteodifferentiation constructs
      exceeded those of the rhBMP-2 group at 1-7 days, and was slightly lower than the
      rhBMP-2 group at 21 days. Mineralization of the rhBMP-2 group was 12-fold that of
      the control constructs at 21 days. In conclusion, although the BMP-2 delivery
      promoted osteodifferentiation, the preosteodifferentiation method and the
      ostegenic media method with hUCMSCs in CPCF were also promising for bone
      regeneration. hUCMSCs may be an effective alternative to the gold-standard bone
      marrow MSCs, which require an invasive procedure to harvest. The novel injectable
      stem cell-CPCF construct may be useful in minimally invasive and other orthopedic
      surgeries.

PMID- 21091342
TI  - Long-term complications of decompressive craniectomy for head injury.
AB  - There is currently much interest in the use of decompressive craniectomy for
      intracranial hypertension. Though technically straightforward, the procedure is
      not without significant complications. A retrospective analysis was undertaken of
      164 patients who had had a decompressive craniectomy for severe head injury in
      the years 2004 to 2009 at the two major hospitals in Western Australia. Eighty
      six patients had a bifrontal decompression and seventy-eight had a unilateral
      decompression. Two patients died due to post-operative care issues. Complications
      attributable to the decompressive surgery were: herniation of the cortex through
      the bone defect (42 patients, 25.6%), subdural effusion (81 patients, 49.4%),
      seizures (36 patients, 22%), hydrocephalus (23 patients, 14%), and syndrome of
      the trephined (2 patients, 1.2%). Complications attributable to the subsequent
      cranioplasty included: sudden death due to massive cerebral swelling in 3
      patients (2.2%), infection requiring removal of the bone flap in 16 patients
      (11.6%), and bone flap resorption requiring augmentation in 10 patients (7.2%).
      After excluding simple complications such as subdural effusion and brain
      herniation through the skull defect and some patients who died as a direct
      consequence of traumatic brain or extracranial injury, 81 patients (55.5%) had at
      least one complication after decompressive craniectomy. The occurrence of at
      least one complication after decompressive craniectomy was significantly
      associated with an increased risk of prolonged stay in the hospital or
      rehabilitation facility (odds ratio 2.54, 95%confidence interval 1.22,5.24,
      p=0.013), after adjusting for predicted risk of unfavorable outcome.

PMID- 21091343
TI  - A comparison between screw- and cement-retained implant prostheses. A literature
      review.
AB  - Implant-supported restorations can be secured to implants with screws (screw
      retained), or they can be cemented to abutments which are attached to implants
      with screws (cement-retained). This literature review discusses the advantages
      and disadvantages of each method of retention from different aspects. These
      aspects include: ease of fabrication and cost, esthetics, access, occlusion,
      retention, incidence of loss of retention, retrievability, clinical prosthesis
      fit, restriction of implant position, effect on peri-implant tissue health,
      provisionalization, immediate loading, impression procedures, porcelain fracture,
      and clinical performance. Peer-reviewed literature published in the English
      language between 1955 and 2010 was reviewed using PubMed and hand searches. Since
      the choice of using either method of retention is still controversial, this
      review article offers some clinical situations that prefer one method of
      retention over the other. The review demonstrated that each method of retention
      has certain advantages and disadvantages; however, there are some clinical
      situations in which it is better to select one method of retention rather than
      the other.

PMID- 21091344
TI  - Tooth-implant connection: a review.
AB  - The aim of this review was to assess the long-term outcomes of restorations
      supported by implants and natural teeth with regard to complications associated
      with implants, teeth, and restorations, as well as the influence on these
      parameters of the connector type used. A net-based search in PubMed was combined
      with a manual search. Clinical studies, reviews, and biomechanical studies were
      included. Information on survival rate, complication rate, incidence of tooth
      intrusion, and, where applicable, type of connector used, was retrieved from the
      clinical studies. Force distribution and types of connectors used were retrieved
      from the biomechanical study. A summary of outcomes was retrieved from the
      reviews. A total of 25 articles were selected for inclusion in this review,
      including clinical studies (15), biomechanical studies (7), and reviews (3).
      Implant success rates ranged from 79.5%-100%. Tooth complications occurred in
      5.4%-11.8% of cases. Complications in the suprastructure were observed in 5%-90%
      of cases. Tooth intrusion presented in a total of 0%-66% of all cases, more often
      in cases with nonrigid connection (0%-66%) than in cases with rigid connection
      (0%-44%). Biomechanical studies show a large difference in stress distribution
      and in dependence on the type of connector used, with most studies demonstrating
      that nonrigid connectors drastically reduce stress on the suprastructure while
      increasing forces on supporting teeth and implants. Long-term success rates for
      tooth-implant connections are lower than for solely implant-supported
      restorations with regard to prognosis for teeth, implants, and suprastructure.
      Use of rigid connectors leads to more favorable clinical outcomes in terms of
      long-term stability, occurrence of complications, and tooth intrusion.

PMID- 21091345
TI  - One-stage full-mouth disinfection as a therapeutic approach for generalized
      aggressive periodontitis.
AB  - BACKGROUND: Data concerning treatment outcomes in patients with generalized
      aggressive periodontitis (GAgP) are limited. The aim of this study is to
      investigate 6-month clinical and microbiologic outcomes of the one-stage full
      mouth disinfection (OSFMD) in the management of patients with GAgP. METHODS:
      Twenty-seven patients with advanced GAgP were included in this prospective follow
      up intervention study. Clinical and microbiologic parameters were collected at
      baseline and 3 and 6 months after the OSFMD. Patient-, tooth-, and site-level
      analyses were carried out. Subgingival samples from moderate (4 to 5 mm) and deep
      (>=6 mm) pocket sites were analyzed using a polymerase chain reaction for
      Aggregatibacter actinomycetemcomitans (previously Actinobacillus
      actinomycetemcomitans), Prevotella intermedia, Porphyromonas gingivalis,
      Tannerella forsythia (previously T. forsythensis), and Treponema denticola.
      RESULTS: The OSFMD resulted in significant improvements in all parameters. After
      6 months, the whole-mouth probing depth (PD) decreased from 4.2 +/- 1.1 mm to 2.8
      +/- 0.6 mm, and the clinical attachment level was reduced from 4.5 +/- 1.2 mm to
      3.4 +/- 1.1 mm (P <0.001). When data were analyzed based on the frequency
      distribution of PD, the number of sites with PD >=5 mm decreased by 61% from
      baseline values, and mean PD reductions of 1.5 and 2.5 mm were noted in moderate
      and deep pockets, respectively. At 6 months, percentages of moderate and deep
      sites free of pathogens were 40% and 27%, respectively. CONCLUSION: The OSFMD may
      be a viable approach to deal with severe GAgP.

PMID- 21091346
TI  - Acute myocardial infarction is reflected in salivary matrix metalloproteinase-8
      activation level.
AB  - BACKGROUND: The aim of this study is to compare salivary and serum biomarker
      levels and degrees of matrix metalloproteinase (MMP) activation between patients
      with acute myocardial infarction (AMI) and systemically healthy patients (non
      AMI) with similar periodontal conditions. METHODS: A total of 92 patients (47 AMI
      and 28 non-AMI patients with gingivitis or periodontitis; and 17 systemically and
      periodontally healthy patients as a control group) were recruited. Clinical
      periodontal measurements were recorded; stimulated whole saliva and serum samples
      were collected. AMI patients were clinically examined within 3 to 4 days after
      admission to the coronary care unit. Saliva samples were analyzed for levels of
      MMP-8, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. Serums
      were tested for MMP-8, MMP-9, TIMP-1, and TIMP-2 levels by immunofluorometric
      assay and enzyme-linked immunosorbent assay. Molecular forms and degree of
      activation of salivary MMP-8, MMP-9, and MMP-13 were analyzed by computer-scanned
      immunoblots. RESULTS: Total salivary MMP-8 assessed by immunofluorometric assay
      method and immunoblot densitometric units was higher in non-AMI than in AMI
      patients' saliva, but a significantly higher percentage of AMI patients' MMP-8
      was activated polymorphonuclear leukocyte (PMN) type (P <0.001) regardless of
      periodontal diagnosis.Serum MMP-8, MMP-9, and TIMP-1 levels were significantly
      higher in AMI (for all markers and all comparisons,P <0.05). Characteristic for
      AMI was dominance of active PMN MMP-8 in saliva [corrected].

PMID- 21091347
TI  - Treatment of Class II molar furcation involvement: meta-analyses of reentry
      results.
AB  - BACKGROUND: Predictable regeneration of lost periodontal tissues in furcations is
      difficult to achieve. This paper investigates the efficacy of different treatment
      modalities for Class II molar furcations. METHODS: Publications in English were
      searched using PubMed, Medline, and Cochrane Library databases combined with hand
      searching from January 1, 1966 to October 1, 2007. The search included randomized
      controlled human trials in molar Class II furcations with over 6 months of
      surgical reentry follow-up. Changes in vertical probing depths, vertical
      attachment levels, and vertical and horizontal bone levels were compared.
      RESULTS: The search identified 801 articles of which 34 of 108 randomized
      clinical trials met the criteria. Thirteen trials had test and control arms
      allowing three meta-analyses: 1) five comparing non-resorbable versus resorbable
      membranes, 2) five comparing non-resorbable membranes versus open flap
      debridement and 3) three comparing resorbable membranes versus open flap
      debridement. There was significant improvement for resorbable versus non
      resorbable membranes mainly in vertical bone fill (0.77 +/- 0.33 mm; [95% CI;
      0.13, 1.41]). Non-resorbable membranes showed significant improvement in vertical
      probing reduction (0.75 +/- 0.31 mm; [95% CI; 0.14, 1.35]), attachment gain (1.41
      +/- 0.46 mm; [95% CI; 0.50, 2.31]), horizontal bone fill (1.16 +/- 0.29 mm; [95%
      CI; 0.59, 1.73]), and vertical bone fill (0.58 +/- 0.11 mm; [95% CI; 0.35, 0.80])
      over open flap debridement. Resorbable membranes showed significant improvement
      in vertical probing reduction (0.73 +/- 0.16 mm; [95% CI; 0.42, 1.05]),
      attachment gain (0.88 +/- 0.16 mm; [95% CI; 0.55, 1.20]), horizontal bone fill
      (0.98 +/- 0.12 mm; [95% CI; 0.74, 1.21]) and vertical bone fill (0.78 +/- 0.19
      mm; [95% CI; 0.42, 1.15]) over open flap debridement. CONCLUSIONS: Guided tissue
      regeneration with the use of resorbable membranes was superior to non-resorbable
      membranes in vertical bone fill. Both types of membranes were more effective than
      open flap debridement in reducing vertical probing depths and gaining vertical
      attachment levels and in gaining vertical and horizontal bone.

PMID- 21091348
TI  - Interleukin-8 gene promoter polymorphism (rs4073) may contribute to chronic
      periodontitis.
AB  - BACKGROUND: The proinflammatory chemokine interleukin (IL)-8 is important in the
      regulation of the inflammatory response. Analyses of the single nucleotide
      polymorphism (SNP) reference sequence (rs) 4073 showed that the A allele
      upregulated IL-8 levels after stimulation with lipopolysaccharides. We
      investigated the association of the SNP rs4073 with chronic periodontitis.
      METHODS: Genotyping was performed by a standard polymerase chain reaction
      restriction fragment length polymorphism assay in 289 genomic DNA samples of
      healthy control subjects and patients with chronic periodontitis; analyses were
      adjusted by multivariate logistic regression modeling. A real-time polymerase
      chain reaction performance was used to detect levels of the IL-8 mRNA. RESULTS:
      The analysis pointed to a statistically significant association of chronic
      periodontitis with the heterozygous TA genotype (P = 0.001); the results showed
      an increase in the frequency of the A allele in the diseased group (36% in the
      control group versus 48% in the periodontitis group). The higher levels of the IL
      8 mRNA were found in the periodontitis group, mainly in individuals who presented
      the TA genotype (P = 0.03). CONCLUSION: The SNP rs4073 was associated with
      chronic periodontitis in non-smoker Brazilian subjects because the frequency of
      the A allele was higher in the disease group than in the control group, and the
      TA genotype was associated with increased levels of IL-8 mRNA transcripts.

PMID- 21091349
TI  - Chlorhexidine controlled-release profile after EDTA root surface etching: an in
      vivo study.
AB  - BACKGROUND: The main objective of the present study was to quantify chlorhexidine
      (CHX) release after the use of CHX-EDTA root surface treatment as a local
      delivery antimicrobial vehicle. METHODS: Twenty non-smoking patients clinically
      diagnosed as having moderate-to-severe chronic periodontitis were selected to
      participate in this study. After cause-related therapy, one site in every patient
      received defect overfill with CHX gel 2% (20 sites). In addition, twenty
      contralateral sites received defect fill of CHX gel after 3 minutes of 24% EDTA
      gel root surface etching (20 sites). Gingival crevicular fluid samples were
      collected at 1, 3, 7, and 14 days post-therapy. RESULTS: The CHX-EDTA group
      showed statistically significantly higher levels of CHX than those of the control
      group at 1, 3, and 7 days. At 14 days, the CHX-EDTA group showed 0.8 mg/mL
      values. CONCLUSION: The use of CHX-EDTA root surface treatment as a local
      delivery antimicrobial improves CHX substantivity.

PMID- 21091350
TI  - Sensitivity of the periodontal pathogen Aggregatibacter actinomycetemcomitans at
      mildly acidic pH.
AB  - BACKGROUND: Aggregatibacter actinomycetemcomitans (previously Actinobacillus
      actinomycetemcomitans), a capnophilic facultative anaerobe, is associated with
      localized aggressive periodontitis and endocarditis. When grown in broth, the
      cells begin to die rapidly after overnight growth. The cells also often lose
      viability on plates within a few days. The aim of this study is to identify the
      cause of the rapid loss of cell viability. METHODS: Cell viabilities, as measured
      by colony forming units, were determined for cells obtained from isolated
      colonies and from the dense part of a streak on plates. The effect of pH on cell
      viability was determined by growing cells in broth at various initial glucose
      concentrations and with or without added bicarbonate. RESULTS: A.
      actinomycetemcomitans cells were highly sensitive to even a mildly acidic pH of
      ~6. Because the bacteria grew at a glucose concentration that is commonly used in
      many laboratories, there was a dramatic decrease in cell viability as the pH went
      <6, which happened long before the culture reached saturation. This was easily
      avoided by using a lower initial glucose concentration, and under these
      conditions, the addition of bicarbonate to the growth medium was not necessary.
      Cells resuspended in buffer without nutrients lost viability much faster at pH 6
      than at a higher pH. On plates, the cell viability was much higher in isolated
      colonies than in the dense area of the streak. CONCLUSIONS: A.
      actinomycetemcomitans cells rapidly lost viability at even a mildly acidic pH.
      The problem was easily rectified by growing cells at a low glucose concentration.

PMID- 21091351
TI  - Effects of platelet-rich plasma on sinus bone graft: meta-analysis.
AB  - BACKGROUND: This meta-analysis investigates the effects of platelet-rich plasma
      (PRP) on the sinus bone graft. METHODS: PubMed, the Cochrane Library, and EMBASE
      were searched in January 2010. RESULTS: Of 61 articles searched, eight controlled
      clinical trials, which included a total of 352 sinus bone graft cases in 191
      patients, were included in the final analysis. In the fixed-effects meta
      analysis, the implant survival was not significantly different between two groups
      in the patient-based data of four studies (relative risk [RR]: 1.02; 95%
      confidence interval [CI]: 0.97 to 1.08) and in the implant-based data of three
      studies (RR: 1.02; 95% CI: 0.99 to 1.04). The bone formation was significantly
      greater in the intervention group in the random-effects model (standardized mean
      difference [SMD]: 1.30; 95% CI: 0.21 to 2.39) in five studies with significant
      heterogeneity (I(2) = 76.2%). The bone-to-implant contact was not significantly
      different between two groups in the random-effects model (SMD: 1.02; 95% CI: 
      1.65 to 3.70) in two studies with significant heterogeneity (I(2) = 82.4%).
      CONCLUSION: The present study indicates that there was sufficient evidence to
      support the use of PRP for bone formation on a sinus bone graft, whereas there
      was no significant effect on the implant survival and bone-to-implant contact.

PMID- 21091352
TI  - Intramarrow bone morphogenetic protein 4 gene delivery improves local bone
      quality in femurs of ovariectomized rabbits.
AB  - BACKGROUND: Poor bone quality at implant recipient site is a major risk factor
      for implant failure. The purpose of this study is to examine the potential of
      intramarrow bone morphogenetic protein 4 (BMP4) gene delivery for local bone
      quality improvement. METHODS: Adenoviral vector encoding human BMP4 (Ad-BMP4) was
      constructed. Adenovirus encoding beta-galactosidase (Ad-LacZ) was used as a
      control virus. Ad-BMP4 and Ad-LacZ were injected into femurs of ovariectomized
      rabbits. The temporal changes in bone mineral density at injected areas were
      determined by repeated measurements by dual-energy x-ray absorptiometry at 0, 1,
      2, 4, and 8 weeks after injection. The effects of gene delivery on cortical bone
      and cancellous bone were evaluated by microcomputed tomography analysis and
      histologic examination at 8 weeks. RESULTS: The bone mineral density of the BMP4
      group was significantly higher than the LacZ group at 4 and 8 weeks by 61% and
      35%, respectively. Results from microcomputed tomography analysis and histologic
      examination at 8 weeks indicated thicker cortical bone and denser cancellous bone
      in the BMP4 group compared to the LacZ group. CONCLUSIONS: Intramarrow gene
      delivery of BMP4 effectively improved local bone quality for at least 8 weeks.
      The sustained delivery of osteogenic factors via local gene therapy approach may
      reduce implant failures associated with poor local bone quality.

PMID- 21091353
TI  - Sinus floor elevation via the maxillary premolar extraction socket with immediate
      implant placement: a case series.
AB  - BACKGROUND: When immediate implant placement is considered for teeth with close
      proximity to the sinus floor, apical extension of the osteotomy is significantly
      limited, and often a staged approach is used. Implant placement into fresh
      extraction sockets and sinus floor manipulation using bone-added osteotome sinus
      floor elevation with implant placement are techniques most often used
      independently or sequentially. Very few reports have described the combined use
      of immediate implant placement in fresh sockets and the bone-added osteotome
      sinus floor elevation technique. METHODS: We present five cases in which a
      maxillary premolar was extracted and an implant placed into the extraction site
      with simultaneous abfracture of the sinus floor using osteotomes. All teeth were
      extracted atraumatically, and sockets carefully debrided and checked for
      integrity of the walls. After ideal osteotomy preparation, particulate bone graft
      was placed in the osteotomy and appropriately sized osteotomes were used for
      sinus floor elevation. After sufficient elevation, implant placement was
      completed and particulate bone was packed in the bone-implant gap when indicated.
      RESULTS: All implants were restored after a minimum healing period of 6 months.
      At the time of final restoration, bone was seen surrounding the implants from the
      apical portion to the most coronal thread. All five implants healed without
      complications and were in function for periods ranging from 6 to 12 months.
      CONCLUSIONS: Immediate implant placement with simultaneous osteotome sinus floor
      elevation is an advantageous combination of two successfully used techniques.
      This combined approach can significantly reduce the treatment time for implant
      therapy in teeth with close sinus proximity and provide the operator with the
      ability to place implants of desired length.

PMID- 21091354
TI  - Ion-deficient environment induces the expression of basolateral chloride channel,
      ClC-3-like protein, in gill mitochondrion-rich cells for chloride uptake of the
      tilapia Oreochromis mossambicus.
AB  - Gill mitochondrion-rich (MR) cells contain different molecules to carry out
      functionally distinct mechanisms. To date, the putative mechanism of Cl(-) uptake
      through the basolateral chloride channel, however, is less understood. To clarify
      the Cl(-)-absorbing mechanism, this study explored the molecular and
      morphological alterations in branchial MR cells of tilapia acclimated to seawater
      (SW), freshwater (FW), and deionized water (DW). Scanning electron microscopic
      observations revealed that three subtypes of MR cells were exhibited in gill
      filament epithelia of tilapia. Furthermore, in DW-acclimated tilapia, the subtype
      I (ion-absorbing subtype) of MR cells predominantly occurred in gill filament as
      well as lamellar epithelia. Whole-mount double immunofluorescent staining
      revealed that branchial ClC-3-like protein and Na(+)/K(+)-ATPase (NKA), the
      basolateral marker of MR cells, were colocalized in tilapia. In SW-acclimated
      tilapia, all MR cells of gill filament epithelia exhibited faint fluorescence of
      ClC-3-like protein. In contrast, only some MR cells in gill filament epithelia of
      FW and DW tilapia expressed basolateral ClC-3-like protein; however, the
      fluorescence was more intense in FW and DW tilapia than in SW fish. In hyposmotic
      groups, the number of MR cells immunopositive for ClC-3-like protein was
      significantly higher in DW-exposed tilapia. Meanwhile, in gill lamellar epithelia
      of DW tilapia, all MR cells (subtype I) were ClC-3-like protein immunopositive.
      Double immunostaining of ClC-3-like protein and Na(+)/Cl(-) cotransporter (NCC)
      revealed that basolateral ClC-3-like protein and apical NCC were colocalized in
      some MR cells in FW and DW tilapia. Moreover, both mRNA and protein amounts of
      branchial ClC-3-like protein were significantly higher in DW-acclimated tilapia.
      To identify whether the expression of branchial ClC-3-like protein responded to
      changes in environmental [Cl(-)], tilapia were acclimated to artificial waters
      with normal [Na(+)]/[Cl(-)] (control), lower [Na(+)] (low Na), or lower [Cl(-)]
      (low Cl). Immunoblotting of crude membrane fractions for gill ClC-3-like protein
      showed that the protein abundance was evidently enhanced in tilapia acclimated to
      the low-Cl environment compared with the other groups. Our findings integrated
      morphological and functional classifications of ion-absorbing MR cells and
      indicated that ion-deficient water elevated the numbers of subtype I MR cells in
      both filament and lamellar epithelia of gills with positive ClC-3-like protein
      immunostaining and increased the expression levels of ClC-3-like protein. This
      study is the first to illustrate the exhibition of a basolateral chloride channel
      potentially responsible for Cl(-) absorption in the ion-absorbing subtype of gill
      MR cells of tilapia.

PMID- 21091355
TI  - Coenzyme Q as an antiadipogenic factor.
AB  - Coenzyme Q (CoQ) is not only the single antioxidant synthesized in humans but
      also an obligatory element of mitochondrial functions. We have previously
      reported CoQ deficiency in white adipose tissue of ob/ob mice. We sought to
      determine (i) whether this deficit exists in all species and its relevance in
      human obesity and (ii) to what extent CoQ could be involved in adipocyte
      differentiation. Here we identified in rodents as well as in humans a specific
      very strong nonlinear negative correlation between CoQ content in subcutaneous
      adipose tissue and obesity indexes. This striking correlation reveals a threshold
      value similar in both species. This relative deficit in CoQ content in adipose
      tissue rapidly took place during the time course of high-fat-diet-induced obesity
      in mice. Adipocyte differentiation was assessed in vitro using the preadipocyte
      3T3-F442A cell line. When CoQ synthesis was inhibited by a pharmacological
      approach using chlorobenzoic acid, this strongly triggered adipose
      differentiation. In contrast, adipogenesis was strongly inhibited when a long
      term increase in CoQ content was obtained by overexpressing human 4-hydroxy
      benzoate acid polyprenyltransferase gene. Altogether, these data suggest that a
      strict level of CoQ remains essential for adipocyte differentiation, and its
      impairment is associated with obesity.

PMID- 21091356
TI  - Pentosan reduces osteonecrosis of femoral head in SHRSP.
AB  - Increased oxidative stress is considered one of the main causes of steroid
      induced osteonecrosis of the femoral head (ONFH). The aim of this study was to
      evaluate the effects of a steroid hormone and pentosan polysulfate sodium
      (pentosan), a heparin analog, in stroke-prone spontaneously hypertensive rats
      (SHRSP) as a model of ONFH. One hundred twenty-three 13-week-old male SHRSP/Izm
      rats were divided into four groups: a control group (group C), pentosan
      administered group (group P), steroid-administered group (group S), and group
      administered pentosan plus steroid (group PS). Methylprednisolone acetate, as the
      steroid hormone, at a dose of 4 mg (15 mg/kg) was administered at 15 weeks of
      age. Pentosan at a dose of 3 mg/day/kg was continuously administered
      intraperitoneally from 13 weeks of age for 4 weeks. Rats were sacrificed at 17
      weeks of age, and heart blood and both femora were collected. Triglyceride levels
      were significantly lower in group PS than in group S, indicating that pentosan
      improves lipid metabolism. The incidence of histologic ONFH was significantly
      lower in group P, at 14.8% (10/71 femoral heads), than in group C, at 30.4%
      (17/56 femoral heads), and significantly lower in group PS, at 40.8% (29/71
      femoral heads), than in group S, at 91.3% (42/46 femoral heads), indicating that
      pentosan markedly inhibits ONFH. Immunohistochemical staining for oxidative
      stress showed that the stainability was significantly lower in group PS than in
      group S. Pentosan seems to reduce the incidence of ONFH in SHRSP by improving
      lipid metabolism and decreasing oxidative stress.

PMID- 21091357
TI  - The relationship between serum C-reactive protein and daily physical activity in
      Japanese hypertensive patients.
AB  - Hypertension (HT) and C-reactive protein (CRP) are risk factors of cardiovascular
      diseases (CVD). The current study's purpose was to investigate the relationship
      between serum CRP levels and daily lifestyles, including physical activity, in
      Japanese HT patients. Lifestyle factors, blood pressure (BP), blood cholesterol,
      glucose, and CRP were measured in a total of 312 HT patients (153 men/159 women,
      mean age: 62.6 y). Women with physical activity of >= 1 time/week showed
      significantly lower CRP levels than those without it (p < 0.05). The data suggest
      that regular physical activity could reduce the CRP levels in HT patients,
      thereby maybe preventing CVD.

PMID- 21091358
TI  - Validation of the FM-800 ambulatory blood pressure monitor according to the
      Association for the Advancement of Medical Instrumentation criteria and the
      International Protocol.
AB  - To validate the FM-800 device (Fukuda Denshi Co., Ltd., Tokyo, Japan) for
      ambulatory blood pressure monitoring (ABPM), this validation study was performed
      based on the European Society of Hypertension (ESH) protocol and the Association
      for the Advancement of Medical Instrumentation (AAMI) criteria. Thirty-three
      participants were included (15 in phase 1 and an additional 18 in phase 2) in the
      ESH protocol. The device was tested on 85 participants according to the AAMI
      criteria, which require a mean device-observers discrepancy within 5 +/- 8 mmHg.
      The tested device passed all the criteria for both systolic blood pressure (SBP)
      and diastolic blood pressure (DBP), and for the Korotkoff and oscillometric
      methods according to the ESH protocol. The test device also fulfilled the AAMI
      accuracy criteria for the 85 participants; the mean +/- SD of the SBP/DBP
      differences between the tested device and the mean of the observer readings were 
      1.1 +/- 4.2/-0.8 +/- 4.2 mmHg for the Korotkoff method and 2.3 +/- 3.9/-2.3 +/-
      3.9 mmHg for the oscillometric method. The FM-800 device for ABPM passed all the
      validation criteria of the ESH and AAMI and can, therefore, be recommended for
      clinical use in an adult population.

PMID- 21091359
TI  - The association of low-grade systemic inflammation with hypertensive retinopathy.
AB  - High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic low-grade
      inflammation. The pathophysiologic mechanism of hypertensive retiopathy (HR) is
      not fully established. Elevated blood pressure (BP) alone does not fully account
      for the extent of retinopathy, other pathogenic mechanisms may be involved, such
      as low-grade inflammation. Therefore, this study was designed to answer the
      following questions. (i) Do hs-CRP levels change in HR? (ii) Is there any
      relation between degree of HR and hs-CRP levels? This study included 84
      hypertensive patients with HR. The hypertensive patients were divided into two
      groups according to the Keith-Wagener classification. Group 1 comprised 42
      patients with grade I HR, and Group 2 comprised 42 patients with grade II HR. We
      selected 42 healthy subjects matched for age, sex, and body mass index (BMI) for
      control group. The level of hs-CRP in group 2 was significantly higher than in
      group 1 group (p = 0.018) and control group (p = 0.001), it was also higher in
      group 1 than in control group (p = 0.002). Also, hs-CRP showed positive
      correlations with degree of HR (r = 0.29, p = 0.017). Our study suggests that
      there is a relationship between HR and hs-CRP levels, which may be associated
      with systemic low- grade inflammation.

PMID- 21091360
TI  - Association analysis about HLA-DRB1, -DQB1 polymorphism and auto-antibodies
      against alpha(1)-adrenergic receptors in Chinese patients with essential
      hypertension.
AB  - The auto-antibodies against alpha(1)-adrenergic receptors (alpha(1)-AAs) with
      agonist activity likes norepinephrine have been discovered in patients with
      essential hypertension but the mechanism of alpha(1)-AA production remains
      unclear. We supposed the alpha(1)-AAs be correlated to the HLA-DQB1 and DRB1
      alleles. Three hundred ninety-six patients with essential hypertension (EH) and
      224 normotensives were enrolled, and DNA typing was detected by protein coupled
      receptor (PCR) amplification with sequence-specific primers. Analysis was
      performed by alpha(2) and logistic regression. There were the significant
      associations of the haplotype HLA-DQB1*0301-DRB1*04 with the prevalence of
      alpha(1)-AAs in hypertensive patients and it obviously added to the risk for the
      alpha(1)-AA production (adjusted P = 0.019, OR 4.037, 95% CI 1.259-12.947). In
      normotensives, the haplotype HLA-DQB1*05-DRB1*04 provided a strong predisposition
      in alpha (1)-AAs production (adjusted P = 0.024, OR 3.922, 95% CI 1.200-12.817).
      These results suggest the HLA-DRB1*04 might be the primary risk alleles
      associated with alpha(1)-AA production on the haplotypes HLA-DQB1*0301-DRB1*04
      and HLA-DQB1*05-DRB1*04 and increased the risk for alpha (1)-AA production.

PMID- 21091361
TI  - Exaggerated blood pressure response to exercise--a new portent of masked
      hypertension.
AB  - Masked hypertension (MHT) is a popular entity with increased risk of developing
      sustained hypertension, heart attack, stroke, and death. Subjects have normal
      blood pressure (BP) at office but elevated values at night so it is difficult to
      diagnose. Exaggerated blood pressure response to exercise (EBPR) is also a
      predictor of future hypertension. To investigate the relationship between these
      two entities, we evaluated 61 normotensive subjects with EBPR. The subjects
      underwent 24-h ambulatory blood pressure monitoring (ABPM). The prevalence of
      masked hypertension among subjects with EBPR was 41%. Body mass index (BMI), non
      high density lipoprotein (HDL) cholesterol, diastolic blood pressure (DBP) at
      peak exercise and recovery, nondipping DBP pattern, and elevated early morning
      average BPs were associated with masked hypertension. In multivariate logistic
      regression analysis, the DBP measured at peak exercise was detected as an
      independent predictor of MHT in subjects with EBPR. Subjects with abnormally
      elevated BP during exercise are prone to MHT, necessitate medical assessment and
      close follow-up for hypertension.

PMID- 21091362
TI  - Acute obstructive apnea produces natriuresis in spontaneously hypertensive rats
      (SHR) by a renal nerve-dependent.
AB  - The role of renal nerve in excretion was investigated during acute obstructive
      apnea (OA) episodes in SHR. The animals (SHR and control, C) were presented for
      renal denervation (D; CD; SHRD) or undenervation (U; CU; SHRU). Tracheal
      catheterization was performed to induce OA via its total occlusion. Urine samples
      were collected every 2 min after 20 s of OA. Obstructive apnea resulted in
      bradycardia, hypotension, and induced elevations in the urinary measurements in
      SHRU, but not in CU. Conversely, the denervation increased in CD, but not in the
      SHRD. Urinary excretion was dependent of renal nerve in SHR during OA.

PMID- 21091363
TI  - Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery
      remodeling in rats.
AB  - Structural remodeling of pulmonary artery plays an important role in maintaining
      sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of
      statins have been reported in systemic hypertension. In this study, we studied
      the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced
      pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats
      were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH
      treated with Los, and PAH treated with Ato. We found that in the Los- or Ato
      treated group, the mean pulmonary arterial pressure, right heart hypertrophy
      index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%)
      were significantly reduced compared to the PAH group. Also in pulmonary arteries
      dissected from rats in the Ato- or Los-treated group, in both mRNA and protein
      levels, the expression of alpha1C subunit of voltage-gated calcium channel
      (Ca(v)alpha1c) was downregulated, while sarcoplasmic/endoplasmic reticulum
      calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1)
      upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating
      channel was increased, whereas its protein level was reduced in the treated
      groups. Our results suggest that atorvastatin or losartan may regress the
      remodeling of the pulmonary artery in pulmonary hypertensive rats, with
      differential expression of calcium regulating channels.

PMID- 21091364
TI  - Left ventricular hypertrophy determines the severity of diastolic dysfunction in
      patients with nonvalvular atrial fibrillation and preserved left ventricular
      systolic function.
AB  - Regression of left ventricular (LV) hypertrophy (LVH) is known to be related to a
      lower incidence of stroke in hypertensive patients with nonvalvular atrial
      fibrillation (NV-AF). However, its mechanism remains controversial. Recently,
      diastolic dysfunction (DD) was reported to be correlated with ischemic stroke in
      NV-AF. We hypothesized that hypertension (HTN) and resultant LVH might be
      associated with the severity of DD in NV-AF. Two hundred and ninety-four patients
      (204 males, age 66 +/- 12 y) with NV-AF with preserved LV systolic function were
      included. Clinical and echocardiographic data were compared between patients with
      enlarged left atrial (LA) volume (n = 237) and patients with normal LA. Age (60
      +/- 12 vs. 67 +/- 11 years), sex (male; 81 vs. 62%), duration of NV-AF (4.1 +/-
      7.8 vs. 45.7 +/- 49.0 months), brain natriuretic peptide (108.3 +/- 129.3 vs.
      236.1 +/- 197.0 pg/mL), right ventricular systolic pressure (24.5 +/- 5.5 vs.
      33.1 +/- 11.1 mmHg), mitral inflow velocity (E [77.4 +/- 22.2 vs. 88.3 +/- 22.0
      cm/s]), LV mass index (LVMI [87.6 +/- 22.2 vs. 105.1 +/- 23.2 g/m(2)]), peak
      systolic mitral annular velocity (S' [7.2 +/- 2.0 vs. 5.8 +/- 1.8 cm/s]), and
      mitral inflow velocity to diastolic mitral annular velocity (E/E' [9.8 +/- 3.4
      vs. 12.1 +/- 4.4]) were significantly different between the two groups,
      respectively (P < 0.05). In multivariate analysis, LVMI was independently
      correlated with increased LA volume (OR: 1.037 [95% CI: 1.011-1.063], P < 0.05),
      whereas HTN was not. LA enlargement, which reflects the severity and chronicity
      of DD, is independently associated with LVH in patients with NV-AF. Therefore,
      regression of LVH with anti-hypertensive treatment may lead to improvement of
      diastolic function and favorable clinical outcomes in hypertensive patients with
      NV-AF.

PMID- 21091367
TI  - Quality of care for veterans with chronic diseases: performance on quality
      indicators, medication use and adherence, and health care utilization.
AB  - This study was conducted to assess and benchmark the quality of care, in terms of
      adherence to nationally recognized treatment guidelines, for veterans with common
      chronic diseases (ie, asthma, chronic obstructive pulmonary disease [COPD],
      coronary artery disease [CAD], diabetes, heart failure, hyperlipidemia [HL]) in a
      Veterans Health Administration (VHA) system. Patients with at least 1 of the
      target diagnoses in the period between January 2002 and mid-year 2006 were
      identified using electronic medical records of patients seen at the James A.
      Haley Veterans' Hospital in Tampa, Florida. The most common diseases identified
      were HL (34%), CAD (21%), and diabetes (19%). The percentage of patients filling
      a prescription for any guidelines-sanctioned pharmacotherapy ranged from 28%
      (heart failure) to 91% (asthma). Persistence to medication ranged from 21% (HL)
      to 63% (asthma), while compliance ranged from 49% (COPD) to 85% (CAD). Most
      patients with diabetes (88%) had at least 1 A1c test in a year, but only 47% of
      patients had A1c values <7%. This study found that quality of care was generally
      good for conditions such as cardiovascular disease and diabetes, but quality care
      for conditions that have not been a primary focus of previous VHA quality
      improvement efforts, such as asthma and COPD, has room for improvement.

PMID- 21091368
TI  - Validation of the Dutch registry of common oral clefts: quality of recording
      specific oral cleft features.
AB  - OBJECTIVE: Since 1997, common oral clefts in the Netherlands have been recorded
      in the national oral cleft registry using a unique descriptive recording system.
      This study validates data on the topographic-anatomical structure, morphology,
      and side of individual anomalies of the primary palate and secondary palate that
      form the oral cleft. DESIGN: Validation study. SETTING: All 15 Dutch cleft palate
      teams reporting presurgery oral cleft patients to the national registry.
      PATIENTS: A random sample of 250 cases registered in the national database with
      oral clefts from 1997 through 2003; of these, 13 cases were excluded. MAIN
      OUTCOME MEASURES: By linking registry data with clinical data, we identified
      differential recording rates by comparing the prevalence, and we measured the
      degree of agreement by computing validity and reliability statistics. RESULTS:
      The topographic-anatomical structures (lip, alveolus, and hard and soft palates)
      of the anomalies had near-perfect interdatabase agreement with a sensitivity of
      88% to 99%. However, when analyzing the individual anomalies in detail
      (morphology and side), validity decreased and depended on morphological severity.
      This association was most evident for anomalies of the secondary palate. For
      example, sensitivity was higher for "complete cleft hard palate" (92%) than for
      "submucous cleft hard/soft palate" (69%). CONCLUSIONS: Overall, the validity of
      Dutch registry data on oral clefts is good, supporting the feasibility of this
      unique recording system. However, when analyzing oral cleft data in detail, the
      quality appears to be related to anatomical location and morphological severity.
      This might have implications for etiologic research based on registry data and
      for guidelines on neonatal examination.

PMID- 21091369
TI  - Continuous bupivacaine infusion post-iliac crest bone graft harvesting in
      pediatric cleft surgery: role and comparison with ketorolac.
AB  - OBJECTIVE: To investigate the use of intravenous ketorolac and iliac crest
      bupivacaine infusion in the management of iliac crest donor-site pain in the
      pediatric cleft population. The null hypothesis was there is no difference with
      respect to pain scores between ketorolac and iliac crest bupivacaine infusion as
      analgesic adjuncts to intravenous opioids. METHODS: A total of 54 children and
      adolescents (27 boys, 27 girls) undergoing alveolar cleft repair or Le Fort I
      osteotomy were assigned randomly in a prospective, single-blinded fashion to one
      of three groups: intravenous ketorolac plus iliac crest normal saline infusion,
      intravenous ketorolac plus iliac crest bupivacaine infusion, or iliac crest
      bupivacaine infusion alone. Iliac crest infusions and ketorolac were administered
      for 48 hours or until discharge, whichever occurred first. All patients received
      morphine via a patient-controlled analgesia device. MAIN OUTCOME MEASURE(S):
      Primary outcome was pain score, and secondary outcomes were morphine consumption
      and satisfaction scores. RESULTS: Pain scores, morphine consumption, and
      satisfaction scores were not significantly different among groups. Estimated
      costs were significantly higher for bupivacaine infusion than intravenous
      ketorolac. CONCLUSIONS: Iliac crest donor-site pain is well managed in this
      patient population. Intravenous ketorolac and iliac crest bupivacaine infusion
      provide comparable analgesia for iliac crest bone graft donor-site pain in
      children and adolescents.

PMID- 21091371
TI  - Diabetes mellitus disease management in a safety net hospital system: translating
      evidence into practice.
AB  - The Louisiana State University Health Care Services Division system assessed the
      effectiveness of implementing a multisite disease management program targeting
      diabetes mellitus in an indigent patient population. A population-based disease
      management program centered on evidence-based clinical care guidelines was
      applied from the system level. Specific clinic modifications and models were
      used, as well as ancillary services such as medication assistance and equipment
      subsidies. Marked improvement in process goals led to improved clinical outcomes.
      From 2001 to 2008, the percentage of patients with a hemoglobin A1c < 7.0
      increased from 45% to 55% on the system level, with some sites experiencing a
      more dramatic shift. Results were similar across sites, which included both small
      provider groups and academic health centers. In order to achieve these results,
      the clinical environment changed to promote those evidence-based interventions.
      Even in complex environments such as academic health centers with several
      provider levels, or those environments with limited care resources, disease
      management programs can be successfully implemented and achieve statistically
      significant results.

PMID- 21091370
TI  - Measuring health-related productivity loss.
AB  - The objective of this study was to determine the relationship between health
      status and productivity loss and to provide estimates of the business
      implications of lost work performance. Health risk appraisal responses from over
      1 million participants were analyzed to determine productivity loss associated
      with several common health conditions and health risks. Propensity scores and a
      matching technique were used to create analysis groups that differed only by
      presence of a particular health condition or risk. Results were monetized and
      multiplied by the average number of employees with conditions or risks to
      illustrate the potential impact of productivity loss to employers. Costs of
      productivity loss were compared to medical costs for the same conditions and
      health risks. Practical benchmarks of lost work performance may help employers
      assess the financial impact of suboptimal health in their own companies.
      Estimates of lost work time can help employers realize the value of maintaining a
      healthy population.

PMID- 21091365
TI  - Long-term effects of Xuezhikang on blood pressure in hypertensive patients with
      previous myocardial infarction: data from the Chinese Coronary Secondary
      Prevention Study (CCSPS).
AB  - Several previous trials from Western population studies have showed that statins
      may help reduce blood pressure (BP). However, randomized clinical data is
      limited. Xuezhikang, a partially extract of red yeast rice, contains a family of
      naturally occurring statins, and has a marked impact on lipids, but it is unknown
      whether Xuezhikang has any effect on BP during long-term follow-up in the Chinese
      population. This is a post-hoc subgroup analysis of a randomized, double-blinded,
      placebo-controlled, parallel group clinical trial, Chinese Coronary Secondary
      Prevention Study (CCSPS). A total of 2704 hypertensive patients with previous
      myocardial infarction (MI) were assigned either to placebo (n = 1341) or to
      Xuezhikang (n = 1363) daily for an average of 4.5 years. The primary outcome was
      the unadjusted changes in mean arterial pressure (MAP) from baseline to 6 months.
      We also assessed systolic blood pressure (SBP), diastolic blood pressure (DBP),
      and pulse pressure. Analysis of covariance was used to calculate the adjusted
      effects of treatment on changes in these outcomes at 6, 12, 24, and 48 months
      post-randomization, after controlling for potential confounders. This analysis
      included 2704/4870 (55.5%) hypertensive patients for whom BP was measured at
      baseline and at least one follow-up visit after randomization. Median duration of
      the follow-up was 4.5 years (54 months), and 25 patients (0.92%) were lost to the
      last follow-up because of adverse effects. The results showed that the unadjusted
      and adjusted changes in MAP, SBP, DBP, or pulse pressure from baseline were not
      significantly different for Xuezhikang or placebo recipients at 6, 12, 24, and 48
      months after randomization. In this post-hoc subgroup analysis, we failed to
      demonstrate any significant reducing effects of Xuezhikang on BP in Chinese
      hypertensive patients with previous MI, suggesting that further prospective study
      on the effects of statins on BP would be needed, especially in high-risk
      patients.

PMID- 21091372
TI  - Case finding with incomplete administrative data: observations on playing with
      less than a full deck.
AB  - Capacity constraints and efficiency considerations require that disease
      management programs identify patients most likely to benefit from intervention.
      Predictive modeling with available administrative data has been used as a
      strategy to match patients with appropriate interventions. Administrative data,
      however, can be plagued by problems of incompleteness and delays in processing.
      In this article, we examine the effects of these problems on the effectiveness of
      using administrative data to identify suitable candidates for disease management,
      and we evaluate various proposed solutions. We build prospective models using
      regression analysis and evaluate the resulting stratification algorithms using R2
      statistics, areas under receiver operator characteristic curves, and cost
      concentration ratios. We find delays in receipt of data reduce the effectiveness
      of the stratification algorithm, but the degree of compromise depends on what
      proportion of the population is targeted for intervention. Surprisingly, we find
      that supplementing partial data with a longer panel of more outdated data
      produces algorithms that are inferior to algorithms based on a shorter window of
      more recent data. Demographic data add little to algorithms that include prior
      claims data, and are an inadequate substitute when claims data are unavailable.
      Supplementing demographic data with additional information on self-reported
      health status improves the stratification performance only slightly and only when
      disease management is targeted to the highest risk patients. We conclude that the
      extra costs associated with surveying patients for health status information or
      retrieving older claims data cannot be justified given the lack of evidence that
      either improves the effectiveness of the stratification algorithm.

PMID- 21091373
TI  - Allowing time for results of physician practice improvement work: an update to "A
      Community-level Effort to Motivate Physician Participation in the National
      Committee for Quality Assurance Diabetes Physician Recognition Program".

PMID- 21091374
TI  - The impact of a proactive chronic care management program on hospital admission
      rates in a German health insurance society.
AB  - Hospital admissions are the source of significant health care expenses, although
      a large proportion of these admissions can be avoided through proper management
      of chronic disease. In the present study, we evaluate the impact of a proactive
      chronic care management program for members of a German insurance society who
      suffer from chronic disease. Specifically, we tested the impact of nurse
      delivered care calls on hospital admission rates. Study participants were insured
      individuals with coronary artery disease, heart failure, diabetes, or chronic
      obstructive pulmonary disease who consented to participate in the chronic care
      management program. Intervention (n  = 17,319) and Comparison (n  = 5668) groups
      were defined based on records of participating (or not participating) in
      telephonic interactions. Changes in admission rates were calculated from the year
      prior to (Base) and year after program commencement. Comparative analyses were
      adjusted for age, sex, region of residence, and disease severity (stratification
      of 3 [least severe] to 1 [most severe]). Overall, the admission rate in the
      Intervention group decreased by 6.2% compared with a 14.9% increase in the
      Comparison group (P  <  0.001). The overall decrease in admissions for the
      Intervention group was driven by risk stratification levels 2 and 1, for which
      admissions decreased by 8.2% and 14.2% compared to Comparison group increases of
      12.1% and 7.9%, respectively. Additionally, Intervention group admissions
      decreased as the number of calls increased (P  =  0.004), indicating a dose
      response relationship. These findings indicate that proactive chronic care
      management care calls can help reduce hospital admissions among German health
      insurance members with chronic disease.

PMID- 21091375
TI  - The economic value of a wellness and disease prevention program.
AB  - The objective of this study was to determine the economic impact of the Hawaii
      Medical Service Association's health promotion/disease prevention program. A
      retrospective analysis of health risk, health claims, and cost was performed
      using a mixed model factorial design for the years 2002-2005 that compared
      program participants to nonparticipants. All analyses were adjusted for
      preexisting observed differences based on sex, age, baseline morbidity, and
      health care costs between participants and nonparticipants using propensity score
      matching method and/or covariates as appropriate. After analyzing data from more
      than 166,000 HMSA members over a 4-year period, participants were found to incur
      consistently lower costs. Predictive modeling of upward cost trajectories
      relative to actual health care costs for participants and risk-matched
      nonparticipants indicated a savings of $350 per participant per year. Those who
      participated in additional wellness programming demonstrated additional cost
      savings. This study illustrates the economic value of a comprehensive health
      promotion program.

PMID- 21091376
TI  - Strategic response by providers to specialty hospitals, ambulatory surgery
      centers, and retail clinics.
AB  - Radical innovation and disruptive technologies are frequently heralded as a
      solution to delivering higher quality, lower cost health care. According to the
      literature on disruption, local hospitals and physicians (incumbent providers)
      may be unable to competitively respond to such "creative destruction" and alter
      their business models for a host of reasons, thus threatening their future
      survival. However, strategic management theory and research suggest that, under
      certain conditions, incumbent providers may be able to weather the
      discontinuities posed by the disrupters. This article analyzes 3 disruptive
      innovations in service delivery: single-specialty hospitals, ambulatory surgical
      centers, and retail clinics. We first discuss the features of these innovations
      to assess how disruptive they are. We then draw on the literature on strategic
      adaptation to suggest how incumbents develop competitive responses to these
      disruptive innovations that assure their continued survival. These arguments are
      then evaluated in a field study of several urban markets based on interviews with
      both incumbents and entrants. The interviews indicate that entrants have failed
      to disrupt incumbent providers primarily as a result of strategies pursued by the
      incumbents. The findings cast doubt on the prospects for these disruptive
      innovations to transform health care.

PMID- 21091377
TI  - Transmitted HIV type 1 drug resistance among individuals with recent HIV
      infection in East and Southern Africa.
AB  - To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data
      from recently HIV-infected African volunteers, we sequenced HIV (pol) and
      evaluated for TDRM the earliest available specimens from ARV-naive volunteers
      diagnosed within 1 year of their estimated date of infection at eight research
      centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The
      prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78
      (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five
      volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data
      suggest an increase in DRMs by year of infection in Zambia (p = 0.004). The
      prevalence observed in Entebbe was high across the entire study. ARV history data
      from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use
      prior to transmission. Among four partners with sequence data available,
      transmission linkage was confirmed and two had the same TDRMs as the newly
      infected volunteer (both K103N). As ARV therapy continues to increase in
      availability throughout Africa, monitoring incident virus strains for the
      presence of TDRMs should be a priority. Early HIV infection cohorts provide an
      excellent and important platform to monitor the development of TDRMs to inform
      treatment guidelines, drug choices, and strategies for secondary prevention of
      TDRM transmission.

PMID- 21091378
TI  - Txl1 and Txc1 are co-factors of the 26S proteasome in fission yeast.
AB  - The 26S proteasome is a large proteolytic particle present in the cytosol and
      nucleus of eukaryotic cells. Most intracellular proteins, including those
      affected by oxidative damage, are degraded by the proteasome. The human
      thioredoxin, Txnl1, is known to associate with the 26S proteasome and thereby
      equips proteasomes with redox capabilities. Here, we characterize the fission
      yeast orthologue of Txnl1, called Txl1. Txl1 associates with the 26S proteasome
      via its C-terminal domain. This domain is also found in the uncharacterized
      protein, Txc1, which was also found to interact with 26S proteasomes. A txl1 null
      mutant, but not a txc1 null, displayed a synthetic growth defect with cut8,
      encoding a protein that tethers the proteasome to the nuclear membrane. Txc1 is
      present throughout the cytoplasm and nucleus, whereas Txl1 co-localizes with 26S
      proteasomes in both wild-type cells and in cut8 mutants, indicating that Txl1 is
      tightly associated with 26S proteasomes, while Txc1 might be only transiently
      bound to the complex. Finally, we show that Txl1 is an active thioredoxin.
      Accordingly, Txl1 was able to reduce and mediate the degradation of an oxidized
      model proteasome substrate in vitro. Thus, Txl1 and Txc1 are proteasome co
      factors connected with oxidative stress.

PMID- 21091379
TI  - Video-based assistance system for training in minimally invasive surgery.
AB  - In this paper, the development of an assisting system for laparoscopic surgical
      training is presented. With this system, we expect to facilitate the training
      process at the first stages of training in laparoscopic surgery and to contribute
      to an objective evaluation of surgical skills. To achieve this, we propose the
      insertion of multimedia contents and outlines of work adapted to the level of
      experience of trainees and the detection of the movements of the laparoscopic
      instrument into the monitored image. A module to track the instrument is
      implemented focusing on the tip of the laparoscopic tool. This tracking method
      does not need the presence of artificial marks or special colours to distinguish
      the instruments. Similarly, the system has another method based on visual
      tracking to localize support multimedia content in a stable position of the field
      of vision. Therefore, this position of the support content is adapted to the
      movements of the camera or the working area. Experimental results are presented
      to show the feasibility of the proposed system for assisting in laparoscopic
      surgical training.

PMID- 21091380
TI  - Portal vein thrombosis and pulmonary artery thromboembolism after laparoscopic
      colectomy.
AB  - Portal vein thrombosis is a rare and potentially lethal complication of
      laparoscopic colectomy. In this paper, we present a case of portal vein
      thrombosis and pulmonary artery thromboembolism on the 11(th) day after
      laparoscopic colectomy without an evident congenital thrombotic disorder.
      Laparoscopic surgeons and their patients should be aware of such events, because
      the patients are usually discharged before the symptoms begin.

PMID- 21091381
TI  - Endovascular image-guided navigation: validation of two volume-volume
      registration algorithms.
AB  - The limited volume covered by intraoperatively acquired CT scans makes the use of
      navigation systems difficult. Preoperative images cover a larger volume of
      interest. Hence, reliable registration of high quality preoperative to
      intraoperative CT will provide the necessary image information required for
      navigation. This study evaluates two algorithms (Siemens, CAMP) for volume-volume
      registration for usage during endovascular navigation. Twenty patients treated
      for abdominal aortic aneurysm were scanned with pre-, intra- and postoperative
      CT. Six data sets were excluded due to variations in image acquisition parameters
      and severe artifacts. Fourteen intra- and postoperative datasets were registered
      ten times with both algorithms, altogether 140 registrations for each program. In
      all data sets five specified landmarks placed by two radiologists were used to
      evaluate registration accuracy. The distance between the paired landmarks in the
      registered intra- and postoperative volumes was measured and the root mean square
      value calculated. Reference registrations were based on rigid body registration
      of the five landmarks in the intra- and postoperative volumes. Registration
      accuracy (mean +/- SD) was for Siemens 5.05 +/- 4.74 mm, for CAMP 4.02 +/- 1.52
      mm and for the reference registrations 2.72 +/- 1.18 mm. The registration
      algorithms differed significantly, p < 0.001.

PMID- 21091382
TI  - pH-sensitive PEG-based micelles for tumor targeting.
AB  - A new acid sensitive nanocarrier based on lipid core micelles has been
      investigated for tumor targeted drug delivery. Sulfadimethoxine-PEG-phospholipid
      unimer (SD-PEG-DSPE) was designed to endow micelles with pH responsiveness in the
      physiopathologic range. The unimer was synthesized according to a two-step
      procedure. Potentiometric analysis showed that SD-PEG-DSPE has pK(a) of 6.7. In
      water, the unimers assembled spontaneously in 20 nm size micelles with 60 MUM
      critical micelle concentration. The particle size was not affected by the pH in
      the 6.2-7.4 range. The micelles loaded paclitaxel very efficiently and released
      the drug slowly regardless the incubation pH. Fluorescence spectroscopy and
      cytofluorimetry carried out by MCF7 tumor cell incubation with labeled SD-PEG
      DSPE micelles at pH 7.4 and 6.2 showed that micelles associate with cells mostly
      at acidic pH with a time-dependent behavior. A cell subpopulation took up the
      nanocarrier more efficiently at pH 6.2. Confocal microscopy confirmed that under
      these conditions the systems are taken up by cells or fuse with cellular
      membrane. Cytotoxicity studies demonstrated that the SD-PEG-DSPE micelles deliver
      more efficiently paclitaxel at pH 6.2 than at neutral pH confirming that the cell
      internalization can be triggered by the external environmental conditions.

PMID- 21091383
TI  - Epidermal growth factor receptor in corneal damage: update and new insights from
      recent reports.
AB  - Agonist and antagonist drugs acting on epidermal growth factor receptor (EGFR)
      signaling are emerging as a new possibility for pharmaceutical study and clinical
      manipulation of some skin and corneal disorders. EGFR activation appears to be
      effective in reducing the time of reepithelialization after corneal wound
      healing, with potential uses in penetrating keratoplasty, refractive surgery,
      alkali burns, diabetic keratopathy, keratopathy following chemotherapy, cornea
      transplantation, and dry eye. Most of the studies show therapeutic advantages of
      human recombinant epidermal growth factor (hrEGF) eye drops without showing
      adverse effects. In contrast, EGFR inhibition delays epithelial cell
      proliferation and stratification during corneal regeneration.The aim of this
      review is to summarize the most seminal discoveries and recent advances so as to
      clarify the role of the EGFR system in corneal physiology and pharmacology.
      Epidermal growth factor eye drops could be a first-choice treatment for promoting
      regeneration in numerous epithelial defects in the medium to long term.

PMID- 21091384
TI  - Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leukocytoclastic
      vasculitis induced by propylthiouracil confirmed by positive patch test: a case
      report and review of the literature.
AB  - A 43-year-old female with antiphospholipid syndrome and Graves' disease developed
      a cutaneous leukocytoclastic vasculitis associated with antineutrophil
      cytoplasmic antibody (ANCA) against myeloperoxidase (MPO-ANCA) and proteinase-3
      (PR3-ANCA), whilst treated with propylthiouracil (PTU). The skin lesions were
      progressively resolved after withdrawal of PTU and treatment with oral steroids.
      Patch testing with PTU at 1%, 5%, and 10% in petrolatum was positive at 48 h.
      Despite positive ANCA titers after 1 year of follow-up, the patient maintains
      complete clinical remission. PTU is a common antithyroid drug, which has been
      known to induce ANCA-positive vasculitis. Although most patients with this rare
      side effect have a good outcome, some fatal cases have been reported. Therefore,
      patients treated with PTU should be carefully followed and monitored, not only
      for their thyroid state but also for early detection of potential serious
      complications of this drug. Early diagnosis and prompt cessation of PTU therapy
      are essential to improve the outcome. Also key aspects of PTU-induced ANCA
      positive vasculitis are reviewed.

PMID- 21091385
TI  - Effect of preparation techniques on the properties of curcumin liposomes:
      characterization of size, release and cytotoxicity on a squamous oral carcinoma
      cell line.
AB  - Curcumin, a chemopreventive agent, was incorporated into liposomes using
      different preparation techniques and characterized for parameters such as drug
      loading efficiency, size, in vitro release and in vitro cytotoxicity on a
      squamous carcinoma cell line. Liposomes were prepared with different methods -
      thin layer evaporation, ethanol injection and sonication methods, respectively,
      obtaining, multilamellar vesicles (MLVs) and small unilamellar vesicles (SUVs).
      The preparation techniques influenced the size, encapsulation efficiency, in
      vitro release and cytotoxicity profiles. Encapsulation efficiency increased with
      decrease in drug to lipid ratio in the following rank order - MLVs > SUVs >
      ethanol injection vesicles. In vitro release and in vitro cytotoxicity were a
      function of the size of vesicle, which varied depending on the preparation
      technique. Based on these results, it can be concluded that different liposomal
      formulations can be employed to achieve unique in vivo needs in cancer
      chemotherapy.

PMID- 21091386
TI  - Alpha-1-syntrophin protein is differentially expressed in human cancers.
AB  - We studied the expression of alpha1-syntrophin (SNTA1) protein in histologically
      confirmed esophageal, stomach, lung, colon, rectal and breast cancerous tissue
      samples. Our results suggest a significant decrease in the expression level of
      SNTA1 protein in both esophageal squamous cell carcinoma (ESCC) and esophageal
      adenocarcinoma (EAC) compared with their respective controls while a significant
      increase in expression of SNTA1 protein compared with the normal tissue was
      observed in breast carcinoma samples. No significant difference in expression of
      SNTA1 protein was observed in stomach, lung, colon and rectal cancers. Our
      results suggest that SNTA1 has a role in carcinogenesis and could possibly be
      used as a novel diagnostic or prognostic marker in esophageal and breast cancers.

PMID- 21091387
TI  - Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by
      oridonin nanosuspension.
AB  - The mechanism for anti-tumor activity of oridonin (ORI) nanosuspension, prepared
      by the high pressure homogenization method, was studied using MCF-7 human breast
      carcinoma cells in vitro. MTT assay, observation of morphologic changes, flow
      cytometric analysis, and western blot analysis indicated that ORI nanosuspension
      could significantly intensify the in vitro anti-tumor activity to MCF-7 cells, as
      compared with ORI solution. Furthermore, ORI nanosuspension induced G2/M stage
      proliferation arrest and apoptosis in MCF-7 cells depending on its concentration.
      In addition, western blot analysis indicated that the pro-caspase-3 protein was
      not cleaved into the activated form and the expression of anti-apoptotic Bcl-2
      protein decreased, on the contrary, the expression of pro-apoptotic Bax protein
      increased in a dose-dependent manner in ORI nanosuspension-treated cells. These
      observations indicated that the anti-tumor activity of ORI nanosuspension was
      intensified by cell-cycle arrest and apoptosis induction.

PMID- 21091388
TI  - Rapid suppression of HIV-RNA is associated with improved control of immune
      activation in Mozambican adults initiating antiretroviral therapy with low CD4
      counts.
AB  - The rapidity of HIV-RNA suppression after initiation of combined antiretroviral
      therapy (cART) may impact immune reconstitution in developing countries, where
      patients initiate cART at low CD4 T cell counts. One hundred and thirty-five HIV
      1 Mozambican adults initiating cART were prospectively followed over 16 months
      within a larger observational study. Plasma HIV-RNA, CD4 counts, and CD8 T cell
      activation were monitored at the pre-cART visit and at 4, 10, and 16 months
      during cART. Of the 89 patients with available HIV-RNA data at pre-cART and 4 and
      10 months post-cART, 68% (60/89) suppressed HIV-RNA at 4 months and were defined
      as "early virological controllers"(EC). Twenty of the 29 remaining patients who
      did not control HIV-RNA at 4 months did so at 10 months and were classified as
      "late virological controllers"(LC). Nine (10%) patients did not control HIV-RNA
      at either time point. Both initiating an EFV-containing cART regimen and having
      pre-cART tuberculosis were significantly associated with early HIV-RNA
      suppression if locked into a multivariate model [EFV OR: 13.6 (95% CI 1.7; 108.1)
      p = 0.014) tuberculosis OR: 11.0 (95% CI 1.4; 87.9) p = 0.024]. EC demonstrated
      significantly lower median activated CD8 T cells at 4, 10, and 16 months post
      cART than did LC. Approximately 63% (12/19) of LC experienced reappearance of
      detectable HIV-RNA at 6 months postcontrol as compared to 15% (2/60) of EC (p =
      0.001). This study suggests that rapid suppression of HIV-RNA may lead to a lower
      rate of reappearance of HIV-RNA, which could impact CD8 T cell activation levels
      in patients initiating cART at low CD4 counts.

PMID- 21091389
TI  - Lumbar radiculopathy caused by foraminal stenosis in rheumatoid arthritis.
AB  - STUDY DESIGN: Case-series study. OBJECTIVE: To describe the clinical
      presentation, characteristic findings of imaging studies, and treatment of lumbar
      radiculopathy caused by foraminal stenosis in rheumatoid arthritis. BACKGROUND.
      Lumbar lesions in rheumatoid arthritis are relatively rare, with a limited number
      of systemic reports. METHODS: Six patients with lumbar radiculopathy caused by
      foraminal stenosis in rheumatoid arthritis were treated. The patients were all
      women with a mean age of 69 years and mean rheumatoid arthritis duration of 15
      years. The medical records and imaging studies of all patients were reviewed.
      RESULTS: The affected nerve roots were L4 in four patients and L3 in two
      patients. Foraminal stenosis was not demonstrated in magnetic resonance images in
      four of the six patients. Selective radiculography with nerve root block
      reproduced pain, manifested blocking effect, and demonstrated compression of the
      nerve root by the superior articular process of the lower vertebra in all
      patients. Conservative treatment was performed on one patient, and surgery was
      conducted for the rest of the five patients; radiculopathy was improved in all
      patients. CONCLUSIONS: Lumbar foraminal stenosis is a characteristic pathology of
      rheumatoid arthritis, and should be kept in mind in the diagnosis of lumbar
      radiculopathy. Selective radiculography is useful in the diagnosis of affected
      nerve roots.

PMID- 21091390
TI  - Improving SAR symptoms with levocetirizine: evaluating active and placebo effects
      in pollen challenge vs. natural exposure studies.
AB  - OBJECTIVE: Despite a plethora of published data on levocetirizine, no meta
      analyses exist on the effect of study design, and covariates like age, gender,
      and baseline symptom severity on treatment response. The objective of this study
      was the efficacy of levocetirizine 5  mg tablets and matching placebo at reducing
      allergy symptoms in adult subjects with seasonal allergic rhinitis under various
      pollen exposure study conditions and by age, gender and baseline symptom
      severity. METHODS: This was a meta-analysis of original reports from randomized,
      double-blind, placebo-controlled studies. Clinical studies without detailed
      reports, open-label, non-randomized and non-controlled studies, or paediatric
      studies, were excluded. Study subjects were divided into an environmental
      exposure (EE) group or a natural exposure (NE) group. RESULTS: Data from 3640
      subjects were analysed (n = 2174 for levocetirizine, n = 1466 for placebo). The
      overall results confirmed the efficacy of levocetirizine 5  mg, with an
      approximately 40% symptom score improvement from baseline, in both the EE and NE
      groups. While levocetirizine showed no gender- or age-related differences in
      efficacy, female subjects responded better to placebo in the EE, but not in the
      NE group; younger subjects (<30 years of age) responded less favourably to
      placebo compared with older subjects (>= 50 years of age). Levocetirizine was
      consistently superior to placebo regardless of baseline symptom score levels. The
      highest significance levels between the active and placebo groups were observed
      in subjects sensitized to animal dander and grass. CONCLUSIONS: Differences
      between an oral antihistamine and placebo in clinical studies of allergic
      rhinitis might be due to a different response to placebo rather than to the
      active drug. Levocetirizine seems to have consistent efficacy regardless of age,
      gender, and baseline scores.

PMID- 21091391
TI  - Prolonged release melatonin in the treatment of primary insomnia: evaluation of
      the age cut-off for short- and long-term response.
AB  - OBJECTIVES: The authors recently reported on efficacy and safety of prolonged
      release melatonin formulation (PRM; Circadin 2  mg) in elderly insomnia patients.
      The age cut-off for response to PRM and the long-term maintenance of efficacy and
      safety were further evaluated by looking at the total cohort (age 18-80 years)
      from that study and subsets of patients aged 18-54 and 55-80 years (for whom the
      drug is currently indicated). DESIGN: Randomised, double-blind, placebo
      controlled trial. SETTING: Multicentre, outpatients, primary care setting.
      METHODS: A total of 930 males and females aged 18-80 years with primary insomnia
      who reported mean nightly sleep latency (SL) >20  min were enrolled and 791
      entered the active phase of the study. The study comprised a 2-week, single-blind
      placebo run-in period followed by 3 week's double-blind treatment with PRM or
      placebo, one tablet per day at 2 hours before bedtime. PRM patients continued
      whereas placebo completers were re-randomised 1:1 to PRM or placebo for 26 weeks
      followed by 2-weeks run-out on placebo. MAIN OUTCOME MEASURES: SL and other sleep
      variables derived from sleep diary, Pittsburgh Sleep Quality Index (PSQI),
      Quality of life (WHO-5), Clinical Global Impression of Improvement (CGI-I) and
      adverse effects, recorded each visit, withdrawal and rebound effects during run
      out. RESULTS: In all, 746 patients completed the 3-week and 555 (421 PRM, 134
      placebo) completed the 6-month period. The principal reason for drop-out was
      patient decision. At 3 weeks, significant differences in SL (diary, primary
      variable) in favour of PRM vs. placebo treatment were found for the 55-80-year
      group (-15.4 vs. -5.5  min, p = 0.014) but not the 18-80-year cut-off which
      included younger patients. Other variables (SL-PSQI, PSQI, WHO-5, CGI-I scores)
      improved significantly with PRM in the 18-80-year population, more so than in the
      55-80-year age group. Improvements were maintained or enhanced over the 6-month
      period with no signs of tolerance. No withdrawal symptoms or rebound insomnia
      were detected. Most adverse events were mild with no significant differences
      between PRM and placebo groups in any safety outcome. CONCLUSIONS: The results
      demonstrate short- and long-term efficacy of PRM in insomnia patients aged 18-80
      years, particularly those aged 55 and over. PRM was well-tolerated over the
      entire 6-month period with no rebound or withdrawal symptoms following
      discontinuation. Study Registry No: ClinicalTrials.gov ID: NCT00397189.

PMID- 21091392
TI  - Evaluation of patients' adherence to statins in Poland.
AB  - INTRODUCTION: High efficacy of statin therapy in primary and secondary prevention
      of coronary heart disease (CHD) has been confirmed in numerous clinical trials.
      However, studies' results do not reflect patient benefits in everyday clinical
      practice. Observed discrepancies are the result of patients' failure to comply
      with medical recommendations regarding both non-pharmacological and
      pharmacological treatment. Non-compliance can lead to serious health and economic
      consequences. OBJECTIVES: The purpose of the presented study was the
      retrospective analysis of compliance in patients treated with statins on the
      basis of Polish reimbursement data from the National Health Fund (NFZ). METHODS:
      Medication Possession Ratio (MPR) was used for the compliance assessment;
      proportion of patients achieving the minimum level of compliance which ensure a
      satisfactory clinical response was also evaluated. Number of days to
      discontinuation was calculated in order to estimate patient persistence
      representing the time over which a patient continues to fill a prescription.
      RESULTS: The results of the analysis indicate that only 12% of the population of
      patients treated with statins demonstrates proper level of both compliance and
      persistence. Statistically significant differences were found among different
      patient groups; however, in all the groups, compliance was lower than the minimal
      level required for clinical benefits. CONCLUSIONS: The study revealed poor
      compliance among patients receiving statin prescriptions for hyperlipidaemia
      treatment. We presume that the most important factor for non-adherence can be
      lack of proper patient education, thus all patients on statin treatment should
      receive sufficient attention, supervision and better information.

PMID- 21091393
TI  - Severe burn injuries and the role of elastin in the design of dermal substitutes.
AB  - Severe burn injuries are a major health problem as they can compromise whole body
      function and result in extensive emotional trauma exacerbated by prolonged
      hospital stay. Burn injury treatment has improved dramatically to increase the
      probability of survival, but burn survivors still suffer from excessive scarring
      and skin contractures, which substantially compromise their health and quality of
      life. Elastin is historically underrepresented in commercial dermal substitutes,
      yet deserves consideration because of its fundamental role in skin structure and
      function. Dermal elastic network is a strong determinant of skin resilience,
      texture, and quality but is not sufficiently regenerated following burn injury.
      In addition to its structural and mechanical roles, elastin has inherent cell
      signaling properties that promote a diverse range of cellular responses including
      chemotaxis, cell attachment, proliferation, and differentiation. Scaffold
      elasticity and regeneration of the elastic fiber system is now recognized as
      integral to the development of functional dermal substitutes. Dermal substitutes
      are intended to replace damaged dermal tissue in severe burn injuries. Elastin
      based dermal substitutes have the potential to decrease wound contraction,
      improve scar appearance and functionality, and contribute to wound healing
      outcomes through a combination of elastin's mechanical and cell signaling
      properties.

PMID- 21091394
TI  - Habitual snoring and asthma comorbidity among pregnant women.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) or habitual snoring and asthma are
      known comorbid conditions in men and non-pregnant women. This comorbidity has not
      been evaluated among pregnant women. We assessed the habitual snoring-asthma
      relationship among pregnant women. METHODS: A cohort of women (N = 1335) were
      interviewed during pregnancy, and we ascertained participants' asthma status and
      collected information about habitual snoring, before and during pregnancy.
      Logistic regression procedures were used to estimate odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: Compared with non-asthmatics, the adjusted
      OR among asthmatics for snoring before pregnancy was 2.13 (95% CI 1.10-4.12). The
      odds of snoring during early pregnancy was 1.79-fold (OR = 1.79; 95% C; 1.07
      3.01). Associations were more pronounced among overweight (>= 25 kg/m(2))
      asthmatics (OR = 5.39; 95% CI 2.27-12.75). CONCLUSIONS: We report a cross
      sectional association of habitual snoring and asthma among pregnant women. If
      confirmed, pregnant asthmatics may benefit from more vigilant screening and
      management of OSA or habitual snoring during pregnancy.

PMID- 21091395
TI  - Evaluation of healthcare resource utilization and costs in employees with pain
      associated with diabetic peripheral neuropathy treated with pregabalin or
      duloxetine.
AB  - OBJECTIVE: To evaluate changes in healthcare resource use and costs after
      initiating pregabalin or duloxetine in employees with pain associated with
      diabetic peripheral neuropathy (pDPN). METHODS: Employees (18-64 years old) with
      a DPN diagnosis and at least one pDPN-related pain medication claim were
      identified using the MarketScan Commercial Database (2005-2008). Propensity
      scored matched pregabalin and duloxetine new starts were evaluated in the 6-month
      pre- and 6-month post-initiation periods. Study outcomes including imputed
      medically-related work loss, prescription and healthcare utilization, and
      associated expenditures were analyzed using univariate statistics and
      multivariate models in a difference-in-difference approach. RESULTS: A total of
      473 employees in each treatment group were identified. Mean age was 53.6 (SD 7.0)
      years for pregabalin and 53.5 (SD 7.4) years for duloxetine. There were no pre
      index differences between groups. Adjusted marginal effects were not
      statistically significant for pre-to-post changes in opioid utilization (p =
      0.328), number of pDPN-related analgesic medications (p = 0.506), all-cause
      healthcare costs (p = 0.895), indirect costs (p = 0.324), or pDPN-attributable
      expenditures (p = 0.359). LIMITATIONS: Claims analysis is limited in accounting
      for all patient and plan differences, and by the reliability of medical claims
      for diagnosis coding. The sample size of the matched cohorts may have limited the
      power of the analysis to detect differences. CONCLUSIONS: There were no
      significant pre-to-post differences between pregabalin and duloxetine treatment
      groups in pDPN-related analgesic medication use, or pDPN-attributable, all-cause,
      and indirect expenditures.

PMID- 21091396
TI  - Resource utilization and healthcare costs for acute coronary syndrome patients
      with and without diabetes mellitus.
AB  - OBJECTIVE: This study compared differences in healthcare costs and resource
      utilization for acute coronary syndrome (ACS) patients with and without diabetes
      mellitus (DM). METHODS: A retrospective cohort study of a large, US employer
      based claims database identified adults hospitalized for ACS between 01/01/2005
      and 12/31/2006 and categorized them based on DM status. Resource utilization and
      costs during the index hospitalization and in the 12-month follow-up period were
      compared for ACS patients with and without DM using the propensity score
      stratification bootstrapping method, adjusting for differences in demographic and
      clinical characteristics. RESULTS: Of 12,502 patients who met selection criteria,
      3,040 (24%) had a history of DM and 9,462 (76%) did not. Patients with DM were
      older, female, and had higher rates of previous cardiovascular and renal
      diseases. After the propensity score stratification, patients with DM incurred
      higher index hospitalization costs ($32,577 vs. $29,150, p < 0.01) as well as
      higher total follow-up healthcare costs ($35,400 vs. $24,080, p < 0.01),
      including higher inpatient ($17,278 vs. $11,247, p < 0.01), outpatient ($12,357
      vs. $8,853, p < 0.01), and pharmacy costs ($5,765 vs. $3,980, p < 0.01).
      LIMITATIONS: General limitations exist with any retrospective claims database
      analysis including potential diagnostic or procedural coding inaccuracies.
      Additionally, the patient population was representative of a working-age
      population with employer-sponsored health insurance and results may not be
      generalizable to other patient populations. CONCLUSIONS: DM is significantly
      associated with increased healthcare resource utilization and costs for ACS
      patients.

PMID- 21091397
TI  - Topical immunomodulators for management of oral mucosal conditions, a systematic
      review; part I: calcineurin inhibitors.
AB  - IMPORTANCE OF THE FIELD: Topical immunomodulators have been used for the
      management of oral mucosal diseases. Topical immunomodulating preparations may
      have utility in local management of oral disease which is resistant to topical
      steroids and oral findings of an immunologic-mediated systemic disease with
      primary or persisting, oral mucosal involvement. AREAS COVERED IN THIS REVIEW:
      This paper is the first part of a systematic review of topical immunomodulators
      for the management of various oral indications focused on calcineurin inhibitors.
      The literature search revealed that data are available for cyclosporine,
      tacrolimus and pimecrolimus. In addition to the review of scientific evidence,
      this paper presents the potential market, the mechanism of action, the
      competitive environment and future development options. WHAT THE READER WILL
      GAIN: The reader will find weighted conclusions for the topical use of the
      calcineurin inhibitors in the management of oral diseases. TAKE HOME MESSAGE:
      Topical calcineurin inhibitors may be useful as a second-line treatment in
      several oral diseases, particularly oral lichen planus.

PMID- 21091398
TI  - A comparison of assisted cough techniques in stable patients with severe
      respiratory insufficiency due to amyotrophic lateral sclerosis.
AB  - Cough can be impaired in ALS. This can result in peak cough flows (PCFs) too low
      for an adequate airway clearance (<270 l/mn). There are several cough assistance
      techniques that aim at a better elimination of airway secretions, but which are
      effective, especially in bulbar patients, is not known. We designed the present
      investigation to compare the PCFs produced by a range of manual and mechanical
      techniques in patients with ALS, in non-bulbar but also in bulbar patients. In
      the whole study population, PCFs ranged from 84 (35-118) l/mn for the spontaneous
      cough manoeuvre to 488 (243-605) l/min for the in/exsufflator (p = 0.0005). In
      the bulbar group, these values were 42 (35-130) l/min versus 436 (244-630) l/min,
      respectively (p = 0.008), and 89 (40-106) l/min versus 491 (192-580) l/min,
      respectively, in the non-bulbar group (p = 0.019). There was no statistically
      significant difference between the bulbar and the non-bulbar groups. The
      in/exsufflator was not always the best tool. We conclude that capacity of
      coughing efforts to produce efficient peak cough flows can be dramatically
      improved with different tools, even in patients with very severe bulbar symptoms
      and that it appears useful to test an array of techniques to optimally tailor
      cough improvement techniques to individual patients.

PMID- 21091399
TI  - Depression in amyotrophic lateral sclerosis.
AB  - Depression is an under-recognized comorbidity associated with amyotrophic lateral
      sclerosis (ALS). The goals of this study were to prospectively estimate the
      prevalence of depression and other ALS related symptoms and to study the impact
      of depression on enrollment in research studies. One hundred and twenty-seven
      people with ALS completed the ALS Depression Inventory (ADI-12) and answered
      questions about ALS related symptoms and research study enrollment preferences.
      Demographics, ALS symptoms, medications, functional status, and research
      enrollment were compared between depressed and non-depressed patients. Results
      showed that the prevalence of mild and severe depression was 29% and 6%,
      respectively. More than one-third of our ALS patients were receiving anti
      depressants to treat depression, sialorrhea, and pseudobulbar affect. Depression
      prevalence was not correlated with disease duration or progression. Except for
      anxiety, none of the ALS related symptoms predicted depression. The presence of
      depression did not have an effect on the decision to enroll in research studies.
      In conclusion, major depression is less common in our ALS cohort than in the
      general population. The diagnosis of depression can be masked by some ALS related
      symptoms and it has no impact on enrollment in ALS clinical trials.

PMID- 21091400
TI  - Use of comprehensive geriatric assessment in general practice: results from the
      'Senta Pua' project in Brazil.
AB  - BACKGROUND: General practitioners (GPs) are responsible for most of elderly
      consultations in Brazil. Being aware of the needs of older adults is important
      for these professionals. A comprehensive geriatric assessment (CGA) is an
      important tool for assessing the elderly. OBJECTIVE: The aim of this study was to
      evaluate (a) whether a CGA can identify previously unknown health problems, and
      (b) whether a CGA is accepted by elderly patients. METHODS: We conducted a cross
      sectional study by inviting all outpatients of the Sao Paulo Air Force Hospital
      aged 60 years and older to participate. Consenting patients were examined using a
      CGA. Health problems revealed by the assessment were compared to those previously
      known from the patients' charts. Patients' acceptability of the CGA was evaluated
      by a short questionnaire. RESULTS: 170 patients were included in the final
      analysis. Mean age was 75.7 years (SD: 8.0 years), 65.8% was female. On average,
      patients had 3.2 (SD: 1.9) geriatric problems gleaned from their charts and 9.0
      (SD: 3.2) revealed by CGA. The most common health problems disclosed by the CGA
      were pneumococcal vaccination more than 3 years earlier, followed by sleep
      disorder, sedentarism, urinary incontinence, fall risk and cognitive impairment.
      The mean duration of CGA was 52 min and patient acceptability was high.
      CONCLUSION: The present study using the CGA in a population of patients aged 60
      and above disclosed, on average, 6 medical problems previously unknown to the GP.
      The acceptability by patients was good.

PMID- 21091401
TI  - Updated evidence in support of diet and exercise interventions in cancer
      survivors.
AB  - BACKGROUND: A growing body of evidence suggests that diet and exercise behaviors
      and body weight status influence health-related outcomes after a cancer
      diagnosis. This review synthesizes the recent progress in lifestyle interventions
      in light of current guidelines put forth by the American Cancer Society (ACS),
      the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR)
      and the American College of Sports Medicine (ACSM). METHODS: The PubMed database
      was searched for terms of cancer survivor(s) or neoplasms/survivor, cross
      referenced with MeSH terms of lifestyle, health behavior, physical activity,
      exercise, body weight, obesity, weight loss, diet, nutrition, and intervention
      studies and limited to randomized controlled trials (RCTs) that had retention
      rates exceeding 75%. RESULTS: There has been an increase in the number and
      methodological rigor of the studies in this area, with 21 RCTs identified in the
      past three years. Results suggest that physical activity interventions are safe
      for cancer survivors and produce improvements in fitness, strength, physical
      function, and cancer-related psychosocial variables, whereas dietary
      interventions improve diet quality, nutrition-related biomarkers and body weight.
      Preliminary evidence also suggests that diet and exercise may positively
      influence biomarkers associated with progressive disease and overall survival
      (e.g., insulin levels, oxidative DNA damage, tumor proliferation rates).
      DISCUSSION: The evidence base regarding health-related benefits of increased
      physical activity, an improved diet, and weight control continues to expand. Due
      to the large (and increasing) number of cancer survivors, more research is needed
      that tests the impact of lifestyle change on health-related outcomes in this
      population, especially research that focuses on high-reach, sustainable
      interventions that recruit diverse, representative samples to help increase the
      generalizability of findings to the population at large. Concurrent research also
      needs to address relative benefit in relation to various subpopulations as
      defined by phenotype, genotype, and/or exposures to treatment, and other
      lifestyle and environmental factors.

PMID- 21091402
TI  - Antiproliferative effect of the serotonin receptor antagonist ondansetron in the
      acute lymphoblastic leukemia cell line REH.

PMID- 21091404
TI  - Auditory steady state responses recorded in multitalker babble.
AB  - OBJECTIVE: The primary purpose of this investigation was to determine the effect
      of multitalker babble on ASSRs in adult subjects with normal hearing (NH) and
      sensorineural hearing loss (HI). The secondary purpose was to investigate the
      relationships among ASSRs, word recognition in quiet, and word recognition in
      babble. DESIGN: ASSRs were elicited by a complex mixed-modulation tonal stimulus
      (carrier frequencies of 500, 1500, 2500, and 4000 Hz; modulation rate of 40 or 90
      Hz) presented in quiet and in babble. The level of each carrier frequency was
      adjusted to match the level of the multitalker babble spectrum, which was based
      on the long term speech spectrum average. Word recognition in noise (WIN)
      performance was measured and correlated to ASSR amplitude and ASSR detection
      rate. STUDY SAMPLE: Nineteen normal-hearing adults and nineteen adults with
      sensorineural hearing loss were recruited. RESULTS AND CONCLUSIONS: The presence
      of babble significantly reduced the ASSR detection rate and ASSR amplitude for NH
      subjects, but had minimal effect on ASSRs for HI subjects. In addition, babble
      enhanced ASSR amplitude at high stimulus levels. ASSR detection rate and ASSR
      amplitude recorded in quiet and babble were significantly correlated with word
      recognition performance for NH and HI subjects.

PMID- 21091403
TI  - A multi-component intervention to promote hearing protector use among
      construction workers.
AB  - Hearing protection devices (HPD) remain a primary method of prevention of noise
      induced hearing loss despite their well-known limitations. A three-pronged
      intervention to increase HPD use was conducted among construction workers and
      included a baseline hearing loss prevention training, follow-up 'toolbox' (TB)
      reinforcement trainings, and use of a personal noise level indicator (NLI). A
      total of 176 subjects on eight sites completed three assessments. Prior to
      intervention, HPDs were used an average of 34.5% of the time and increased
      significantly, up about 12.1% after intervention and 7.5% two months after
      interventions were completed. The increase in HPD use was greatest among the
      group receiving both TB and NLI interventions; up about 25% from baseline, and
      this group was about two times more likely to use HPDs than the BL (baseline)
      training only group. This study demonstrates the mild impact of a well
      constructed HPD use training and provides support for the additional use of a
      personal NLI to increase use of HPDs among construction workers. The most
      effective procedures for using such instruments require further exploration.

PMID- 21091405
TI  - Very preterm gestation and breastmilk cytokine content during the first month of
      lactation.
AB  - OBJECTIVE: High susceptibility to infection and deficient cytokine production in
      newborns make breastmilk beneficial, especially for very preterm-born infants.
      This study was conducted to identify the association between very preterm
      gestation and levels of pro- and anti-inflammatory cytokines in transitional and
      mature breastmilk during the first month of lactation after adjustment for mode
      of delivery and parity. STUDY DESIGN: Four samples of breastmilk (6-8, 13-15, 20
      22, and 27-29 days) were collected from each mother after term or very preterm
      delivery at gestational age of less than 32 weeks. We measured the concentration
      of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-13, and tumor necrosis factor
      alpha (TNF-alpha) in the milk samples using a multiplex biometric immunoassay.
      RESULTS: Fifteen mothers of very preterm infants and five term-born infants
      provided 80 samples of breastmilk. We found that delivery at very preterm
      gestation was linked with lower IL-8 (687 +/- 208 pg/dL, p < 0.003) and higher IL
      10 (27.8 +/- 14.2 pg/dL, p < 0.01) levels in transitional breastmilk.
      Significantly decreased IL-8 levels were also seen in mature preterm milk
      samples. Cesarean delivery was associated with increased breastmilk TNF-alpha and
      IL-6 (p < 0.01-0.05), but gestational age was not. CONCLUSIONS: Very preterm
      gestation does not substantially impact the cytokine content of breastmilk during
      the first month of lactation, which can be beneficial for the regional and
      systemic immune response of the very preterm infant with confirmed impairment of
      innate and adaptive immunity.

PMID- 21091406
TI  - An evaluation of Well Ways, a family education programme for carers of people
      with a mental illness.
AB  - OBJECTIVES: Family education programmes aim to improve the well-being of carers
      of people with a mental illness. We evaluated the effectiveness of one such
      programme, Well Ways, in reducing negative care-giving consequences. METHOD: We
      employed a pre-post design to evaluate the effectiveness of Well Ways in a
      naturalistic setting using a sample of carers of people with a mental illness.
      The Involvement Evaluation Questionnaire, a measure of care-giving consequences
      including worrying, tension, urging and supervision, and incorporating the
      General Health Questionnaire-12 (GHQ-12), was completed by 459 carers before and
      after participation in Well Ways. RESULTS: Participants' worrying, tension,
      urging and distress (GHQ-12) were significantly lower following completion of the
      programme. These improvements were maintained at 3 and 6 month follow up. Carers
      of people with a psychotic disorder experienced significantly greater reductions
      in worrying than did other carers. Females reported significantly greater
      reductions in tension than did males. CONCLUSIONS: Findings indicated support for
      the effectiveness of the Well Ways programme in reducing negative care-giving
      consequences for families of people with a mental illness. Given the evidence of
      poor psychological health and negatively appraised family relationships observed
      at baseline, these findings highlight the need for programmes such as Well Ways.

PMID- 21091407
TI  - Avatar-mediated training in the delivery of bad news in a virtual world.
AB  - BACKGROUND: Delivering bad news to patients is an essential communication skill
      for physicians. Educators commonly use standardized patient (SP) encounters to
      train physicians in the delivery of bad news. It is expensive to use actors, for
      logistical reasons such as travel and scheduling, and there are limits to the
      characters and conditions an actor can portray in teaching encounters. Thus we
      studied the feasibility of creating SP avatars in a virtual world for the task of
      training medical trainees to deliver bad news. The SP avatars are easily
      customized for different scenarios and amenable to distance learning. METHODS: We
      recruited 10 medical trainees to interact with a standardized female avatar in a
      three-dimensional simulated clinic, where the trainee was to inform the avatar of
      her newly diagnosed breast cancer. The trainee evaluated his or her self-efficacy
      in delivering bad news via an affective competency score (ACS) before and after
      the encounter. Two palliative care specialists evaluated each trainee's
      performance using the Bad News Assessment Schedule and the performance ACS.
      RESULTS: The self-efficacy ACS scores of the trainees improved overall: before,
      20 +/- 4, versus after, 24 +/- 3, p = 0.001 (maximum score = 30). All
      participants considered the experience positive and commended the novel approach,
      although noting that the avatars were not able to portray body language cues.
      CONCLUSION: Participants viewed the avatar-mediated training as an excellent
      approach for learning how to deliver bad news but believed it could not
      substitute for real patient interactions. However, participant self-efficacy
      improved, which suggests that avatar-mediated training in a virtual world is a
      viable educational approach for skill training in delivering bad news.

PMID- 21091408
TI  - Patient referral and the physiotherapist: three decades later.

PMID- 21091409
TI  - Physiotherapists should ensure their representation in measures of the quality of
      patient care.

PMID- 21091412
TI  - Inter-rater reliability for measurement of passive physiological movements in
      lower extremity joints is generally low: a systematic review.
AB  - QUESTION: What is the inter-rater reliability for measurements of passive
      physiological or accessory movements in lower extremity joints? DESIGN:
      Systematic review of studies of inter-rater reliability. PARTICIPANTS:
      Individuals with and without lower extremity disorders. OUTCOME MEASURES: Range
      of motion and end-feel using methods feasible in daily practice. RESULTS: 17
      studies were included of which 5 demonstrated acceptable inter-rater reliability.
      Reliability of measurements of physiological range of motion ranged from Kappa 
      0.02 for measuring knee extension using a goniometer to ICC 0.97 for measuring
      knee flexion using vision. Measuring range of knee flexion consistently yielded
      acceptable reliability using either vision or instruments. Measurements of end
      feel were unreliable for all hip and knee movements. Two studies satisfied all
      criteria for internal validity while reporting acceptable reliability for
      measuring physiological range of knee flexion and extension. Overall,however,
      methodological quality of included studies was poor. CONCLUSION: Inter-rater
      reliability of measurement of passive movements in lower extremity joints is
      generally low. We provide specific recommendations for the conduct and reporting
      of future research. Awaiting new evidence, clinicians should be cautious when
      relying on results from measurements of passive movements in joints for making
      decisions about patients with lower extremity disorders.

PMID- 21091413
TI  - Risk factors for the first episode of low back pain in children are infrequently
      validated across samples and conditions: a systematic review.
AB  - QUESTION: What risk factors have been identified for the first episode of low
      back pain in children and adolescents? Have these risk factors been validated?
      DESIGN: Systematic review of prospective studies designed to identify possible
      modifiable and non-modifiable risk factors for the onset of low back pain in
      children and adolescents. PARTICIPANTS: School children aged up to 18 years
      without low back pain at enrolment. RESULTS: Five studies were included in the
      review. The included studies varied considerably in methods used to gather data,
      definitions of low back pain, and recall periods for an episode of low back pain.
      Forty-seven possible risk factors had been assessed for association with a first
      episode of low back pain in children. Of these, 13 were significantly associated
      with a first episode of low back pain. No risk factor was found to be associated
      with future low back pain in children in more than one study. CONCLUSION:
      Inconsistency in definitions of low back pain, pre-defined recall periods, and
      methods used to collect and analyse data limit conclusions that can be drawn
      about factors that identify children at risk of developing low back pain. As no
      risk factor has been validated in independent investigation, we have no certainty
      that any factor places children at risk of developing low back pain.

PMID- 21091414
TI  - A postoperative shoulder exercise program improves function and decreases pain
      following open thoracotomy: a randomised trial.
AB  - QUESTION: Does a postoperative physiotherapy exercise program incorporating
      shoulder exercises improve shoulder function, pain, range of motion, muscle
      strength, and health-related quality of life in patients undergoing elective
      pulmonary resection via open thoracotomy? DESIGN: Randomised trial with concealed
      allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS: 76
      patients who underwent pulmonary resection via open thoracotomy. INTERVENTION:
      All participants received standard medical and nursing care involving a clinical
      pathway. The experimental group also received physiotherapy interventions that
      included daily supervised, progressive exercises until discharge and a
      postoperative exercise booklet on discharge. OUTCOME MEASURES: Preoperatively and
      up to 3 months postoperatively pain was measured with a numerical rating scale,
      shoulder function with the Shoulder Pain and Disability Index, and quality of
      life with the Short Form-36. Shoulder range of motion and muscle strength were
      measured in a subgroup. RESULTS: The experimental group had 1.3 units (95% CI 0.3
      to 2.2) less shoulder pain (scored /10) and 2.2 units (95% CI 0.2 to 4.3) less
      total pain (scored /30) at discharge, and 7.6% (95% CI 1.7 to 13.6) better
      function at 3 months. The Short Form-36 physical component score was 4.8 points
      (95% CI -0.3 to 10.0) better for the experimental group than the control group at
      3 months. Differences between groups in all range of motion and strength measures
      were small and statistically non-significant. CONCLUSION: A physiotherapist
      directed postoperative exercise program resulted in significant benefits in pain
      and shoulder function over usual care for patients following open thoracotomy.
      TRIAL REGISTRATION: ANZCTRN 12605000201673.

PMID- 21091415
TI  - Aerobic exercise during pregnancy improves health-related quality of life: a
      randomised trial.
AB  - QUESTION: Does supervised aerobic exercise during pregnancy improve health
      related quality of life in nulliparous women? DESIGN: Analysis of secondary
      outcomes of a randomised trial with concealed allocation, blinded assessors, and
      intention-to-treat analysis. PARTICIPANTS: 64 nulliparous, pregnant women
      attending for prenatal care at one of three tertiary hospitals. INTERVENTION: The
      experimental group completed a 3-month supervised exercise program, commencing at
      16 to 20 weeks of gestation. Each session included walking (10 min), aerobic
      exercise (30 min), stretching (10 min), and relaxation (10 min). The control
      group continued usual activities and performed no specific exercise. OUTCOME
      MEASURES: The primary outcome was health-related quality of life assessed by the
      Colombian version of the Medical Outcome Study Short-Form Health Survey at
      baseline and immediately after the 3-month intervention. RESULTS: Fifty women
      completed the study. After the 3-month intervention, the experimental group had
      improved their health-related quality of life more than the control group in the
      physical component summary of the questionnaire by 6 points (95% CI 2 to 11), the
      physical function domain (7 points, 95% CI 0 to 14), the bodily pain domain (7
      points, 95% CI 1 to 13) and the general health domain (5 points, 95% CI 1 to 10).
      CONCLUSIONS: A supervised 3-month program of primarily aerobic exercise during
      pregnancy improves health-related quality of life. TRIAL REGISTRATION:
      NCT00741312.

PMID- 21091416
TI  - The rotator cuff muscles are activated at low levels during shoulder adduction:
      an experimental study.
AB  - QUESTION: During isometric shoulder adduction in normal subjects, do the rotator
      cuff muscles activate more than other shoulder muscles? Are the activation
      patterns influenced by shoulder abduction angle or load? DESIGN: A within
      participant, repeated measures experimental study. PARTICIPANTS: 15 healthy
      adults. INTERVENTION: Participants performed an isometric adduction exercise at
      30 degrees , 60 degrees , and 90 degrees  abduction in the scapular plane and at
      25%, 50%, 75%, and 100% load. OUTCOME MEASURES: During the exercises, a
      combination of indwelling and surface electromyographic recordings were taken
      from 11 shoulder muscles: supraspinatus, infraspinatus, subscapularis, pectoralis
      major, teres major, latissimus dorsi, rhomboid major, serratus anterior, lower
      trapezius, upper trapezius, and deltoid. RESULTS: At 100% load, mean rotator cuff
      activation levels were low (supraspinatus at 3% of its maximum voluntary
      contraction, infraspinatus 27%, and subscapularis 27%) and significantly less
      than the activation levels of rhomboid major (81%), latissimus dorsi (103%), and
      teres major (76%) (F10,140 = 15.5, p < 0.01). No significant difference in
      activity levels of the rotator cuff muscles were recorded when isometric
      adduction was performed at 30 degrees , 60 degrees , or 90 degrees  abduction (p
      > 0.89). Among the muscles activated above minimum levels (> 10% of maximum
      voluntary contraction), mean activation levels increased as load increased (F3,42
      = 72.0, p < 0.01) CONCLUSION: Since isometric adduction in normal subjects does
      not produce moderate to high activation levels in any of the rotator cuff muscles
      tested, these results do not support the use of shoulder adduction to identify
      rotator cuff muscle dysfunction or strengthen the rotator cuff muscles.

PMID- 21091418
TI  - Inaccuracies in laser therapy meta-analysis for neck pain?

PMID- 21091417
TI  - Walking aid use after discharge following hip fracture is rarely reviewed and
      often inappropriate: an observational study.
AB  - QUESTIONS: What walking aid prescription occurs at discharge after hip fracture?
      What changes in walking aid use occur in the following six months? Who initiates
      changes in walking aids and why? DESIGN: Prospective longitudinal observational
      study. PARTICIPANTS: 95 community-dwelling older adults who had undergone
      surgical treatment of a hip fracture. OUTCOME MEASURES: Range of walking aids
      prescribed at discharge and participants' recall of advice about progression were
      recorded. Progression of walking aids was observed fortnightly over 6 months.
      With any change in walking aid use, an independent physiotherapist determined if
      it was appropriate and participants reported the reason for the change. RESULTS:
      Most participants were discharged from their final inpatient setting with a
      wheeled frame (92%). Eighty-two (86%) participants were not aware of any goals
      set by the physiotherapist for the first 6 months and 89 (94%) stated that a
      review time had not been set. Despite this, 78 (82%) participants changed their
      walking aid, on average 8 weeks (SD 6) after discharge. However, 32% of those who
      changed their walking aids were using an inappropriate aid or using it
      incorrectly. Six months after discharge, 40% of participants had not returned to
      using their pre-morbid indoor aid and 50% their outdoor aid. CONCLUSION: A review
      of walking aid by a physiotherapist is rare within six months after discharge
      following hip fracture. Most patients make their own decision about what walking
      aid is most appropriate. This has safety implications in a group at high risk of
      falls.

PMID- 21091420
TI  - Apoptosis: its functions and control in the ocular lens.
AB  - The ocular lens is a non-vascular and non-innervated transparent organ that plays
      an important role in vision processing. This unique organ is derived from the
      embryonic ectoderm of the brain region through a complicated differentiation
      process in which apoptosis plays a key role. First, when the committed ectoderm
      becomes thickened and invaginated, the defined number of cells required to form
      the lens vesicle is partially determined by apoptosis. Second, separation of lens
      vesicle from the above corneal ectoderm is executed through apoptosis of the lens
      stalk cells. Finally, differentiation of the lens epithelial cells is controlled
      by the regulators, most of which are involved in control of apoptosis at multiple
      signaling steps. The lens is also characterized by continuous growth and
      differentiation in the adulthood. Through the different stages of growth and
      differentiation in the adult lens, various stress conditions can induce apoptosis
      of the lens epithelial cells, leading to eventual non-congenital
      cataractogenesis. The present review summarizes the current knowledge on the
      functions and regulators of apoptosis in the ocular lens.

PMID- 21091421
TI  - Gap junctions or hemichannel-dependent and independent roles of connexins in
      cataractogenesis and lens development.
AB  - In the last decade or so, increasing evidences suggest that the mutations of two
      connexin genes, GJA3 and GJA8, are directly linked to human congenital cataracts
      in North and Central America, Europe and Asia. GIA3 and GIA8 genes encode gap
      junction-forming proteins, connexin (Cx) 46 and Cx50, respectively. These two
      connexins are predominantly expressed in lens fiber cells. Majority of identified
      mutations are missense, and the mutated sites are scattered across various
      domains of connexin molecules. Genetic deletion of either of these two genes
      leads to the development of cataracts; however, the types of cataracts developed
      are distinctive. More interestingly, microphthalmia is only developed in Cx50,
      but not Cx46 deficient mice, suggesting the unique role of Cx50 in lens cell
      growth and development. Knockin studies with the replacement of Cx46 or Cx50 at
      their respective gene locus further demonstrate the unique properties of these
      two connexins. Furthermore, the function of Cx50 in epithelial-fiber
      differentiation appears to be independent of its conventional role in forming gap
      junction junction channels. Due to their specific functions in maintaining lens
      clarity and development, and their malfunctions resulting in lens
      cataractogenesis and developmental impairment, connexin molecules could be
      developed as potential drug targets for therapeutic intervention for treatment of
      cataracts and other eye disorders. Recent advances in basic research of lens
      connexins and the discoveries of clinical disorders as a result of lens connexin
      dysfunctions are summarized and discussed here.

PMID- 21091422
TI  - Critical appraisal of ex vivo expansion of human limbal epithelial stem cells.
AB  - The stem cells (SCs) of the corneal epithelium located in the limbal basal layer
      are the ultimate source to maintain corneal epithelial homeostasis. Like other
      adult tissue-specific SCs, self renewal and fate decision of limbal SCs are
      regulated by a specialized in vivo microenvironment, termed "niche". Loss of
      limbal SCs or dysfunction of the limbal niche renders corneas with a unique
      clinical disease labeled limbal stem cell deficiency (LSCD). Besides
      transplantation of autologous or allogeneic limbal SCs or amniotic membrane, a
      new strategy of treating LSCD is to transplant a bio-engineered graft by
      expanding limbal SCs ex vivo. Herein, we conduct a critical appraisal of six
      protocols that have successfully been practiced in treating human patients with
      LSCD, and identify issues whether niche regulation has been disrupted or
      maintained during isolation and expansion. Consequently, we propose a future
      direction that may circumvent the potential pitfalls existing in these
      conventional protocols by preserving the interaction between limbal SCs and their
      native niche cells during isolation and expansion. Such an approach may one day
      help realize considerable promise held by adult SCs in treating a number of
      diseases.

PMID- 21091423
TI  - Pharmacotherapies for glaucoma.
AB  - Glaucoma is a group of progressive optic neuropathies in which the axons in the
      optic nerve are injured, retinal ganglion cell numbers are reduced and vision is
      gradually and permanently lost. The only approved and effective way to treat
      glaucoma is to reduce the intraocular pressure (IOP). This is usually
      accomplished by surgical and/or pharmacological means. Drugs designed to reduce
      IOP target one or more of the parameters that maintain it. These parameters
      (collectively known as aqueous humor dynamics) are the production rate of aqueous
      humor, the pressure in the episcleral veins and the drainage of aqueous humor
      through the trabecular or uveoscleral outflow pathways. Intraocular pressure
      lowering drugs can be classified as inflow or outflow depending on whether they
      reduce aqueous humor inflow into the anterior chamber or improve aqueous humor
      outflow from the anterior chamber. Inflow drugs, like beta adrenergic antagonists
      and carbonic anhydrase inhibitors, reduce the rate of aqueous humor production.
      Outflow drugs, like prostaglandin analogs, cholinergic agonists and
      sympathomimetics, increase the rate of drainage through the uveoscleral outflow
      pathway and/or increase the facility of outflow through the trabecular meshwork.
      Some drugs have mixed inflow/outflow effects. This review summarizes the
      pharmacological treatments for glaucoma in use today and some new drugs showing
      potential for use in the future.

PMID- 21091426
TI  - Expression and functions of heat shock proteins in the normal and pathological
      mammalian eye.
AB  - Heat shock proteins (Hsps) are expressed in mammalian embryonic, adult and aging
      lens, cornea and retina. These proteins, particularly those belonging to the
      family of small Hsps, such as alphaA-crystallin (HspB4) and alphaB-crystallin
      (HspB5), play important roles in the differentiation of lens cells and are
      essential for the maintenance and protection of the supraorganization of proteins
      in differentiated corneal and lens fiber cells. Hsps are molecular chaperones
      characterized by their protective activity against different types of stress.
      They also have anti-apoptotic and anti-oxidant functions that help lens and
      corneal cells to better cope with the oxidative conditions that result from light
      induced injuries. They are also effective to protect the retina against the high
      rate of oxidative metabolism observed in this tissue. The goal of this review is
      to highlight recent works describing the expression and function(s) of the
      different Hsps as an attempt to better understand their roles in the normal and
      pathological eye. Particular emphasis is given to the alpha-crystallin
      polypeptides which, in addition to their protective functions, are key structural
      polypeptides that are essential for the refractive and light focusing properties
      of the lens, a property demonstrated by the caractogenic potential of their
      mutation.

PMID- 21091425
TI  - SUMOylation in ocular development and pathology.
AB  - SUMOylation, a posttranslational modification process in which SUMO, the small
      ubiquitin-related modifier or small ubiquitin-like modifier, is added to the
      target proteins, plays an important role in regulating a variety of cellular
      processes including protein-protein interactions, subcellular localization,
      protein-DNA interactions and enzyme activity. This process adds another layer of
      control in eukaryote gene expression, and it regulates both transcriptional
      activation and repression. In the present review, we summarized the currently
      emerging information regarding the function of SUMOylation in ocular development
      and pathology.

PMID- 21091427
TI  - The relationship between inflammation, platelet activation and antiplatelet
      resistance.
AB  - Even though there is a strong evidence suggestive of benefits and safety of dual
      (aspirin plus clopidogrel) antiplatelet therapy, decreased responsiveness or
      "resistance" to mono- and/or dual antiplatelet therapy has been described in
      association with an increased thrombotic risk. Various mechanisms contribute to
      antiplatelet resistance, with abundant production of inflammatory markers being
      of particular importance. The current review overviews implications of
      inflammation in antiplatelet resistance.

PMID- 21091429
TI  - Modeling the effect of selected cyclodextrins on nifedipine solubility.
AB  - Nifedipine is a dihydropyridine calcium channel antagonist effective in the
      clinical management of cardiovascular disease. Due to nifedipine's poor water
      solubility and erratic bioavailability, complexation with selected cyclodextrins
      was studied in order to overcome these limitations. The aim was to develop a
      quantitative structure property relationship (QSPR) to identify cyclodextrin
      molecular properties important in complex formation and provide a predictive tool
      which would be valuable during preformulation studies. The QSPR developed
      indicates that the major driving forces for nifedipine complexation, in addition
      to cyclodextrin concentration, are hydrophobicity and Van der Waals interactions
      (3D solubility parameters, hydrophilic surface area and differential connectivity
      index).

PMID- 21091430
TI  - Asparaginyl-tRNA synthetase pre-transfer editing assay.
AB  - Aminoacyl-tRNA synthetases (AARSs) are a structurally heterogeneous family of
      enzymes present in prokaryotes, archaea and eukaryotes. They catalyze the
      attachment of tRNA to its corresponding amino acid via an aminoacyl adenylate
      intermediate. Errors in protein synthesis will occur if an incorrect amino acid
      is attached to the tRNA. To prevent such errors, AARSs have evolved editing
      mechanisms that eliminate incorrect aminoacyl adenylates (pre-transfer editing)
      or misacylated tRNAs (post-transfer editing). Various AARSs are the targets of
      natural antibiotics and are considered validated targets for chemotherapy. We
      have developed a high-throughput screening (HTS) assay measuring the pre-transfer
      editing activity of pathogen-derived asparaginyl-tRNA synthetase (AsnRS). This
      was achieved by monitoring the formation of pyrophosphate via cleavage to
      phosphate, which was quantified by reaction with Malachite Green. L-Aspartate
      beta-hydroxamate, an asparagine analogue, was most effective in promoting the
      editing activity of AsnRS from Brugia malayi (BmAsnRS) and Staphylococcus
      epidermidis (SeAsnRS) with KM values close to 100 mM. The assay sensitivity was
      enhanced by the thiol agents, DTT and L-Cysteine, which significantly increased
      the turn-over of aminoacyl adenylate by BmAsnRS, but not SeAsnRS. The HTS assay
      was used to screen a library of 37,120 natural-product extracts for inhibitors of
      BmAsnRS. A small number of extracts that inhibited the pre-transfer editing by
      BmAsnRS was identified for future isolation of the active component(s). The
      principle of this assay can be applied to all enzymes having a pre- or post
      editing activity.

PMID- 21091428
TI  - Air pollution, platelet activation and atherosclerosis.
AB  - Atherosclerosis begins in early life. The role of platelets is well-documented
      from its early stages. A wealth of evidence associates atherosclerotic
      cardiovascular disease with inflammatory diseases. The role of environmental
      factors, including air pollution, remains overlooked. Some studies have
      documented the effect of air pollution on inflammatory and pro-thrombotic factors
      implicated in the progression of cardiovascular diseases. In particular, the
      increase of platelet count and platelet hyper-reactivity towards agonists are
      emerging as markers of hematologic and hemostatic changes in response to the
      exposure to air pollutants. The systemic pro-inflammatory and pro-thrombotic
      response to the inhalation of fine and ultrafine particulate matters is seemingly
      associated with platelet activation. This association may have a clinical
      significance, particularly in the presence of cardiometabolic risk factors, and
      may indicate the need for anti-platelet treatment. It is of particular relevance
      to further study the significance of platelet activation and anti-platelet
      therapies in primordial/primary preventive measures in children and adolescents
      at risk of accelerated atherosclerosis.

PMID- 21091431
TI  - Chitosan formulations as carriers for therapeutic proteins.
AB  - Protein drugs represent a significant part of the new pharmaceuticals coming on
      the market every year and are now widely spread in therapy to treat or relief
      symptomatology related to many metabolic and oncologic diseases. The delivery of
      therapeutic proteins is still a major drawback against their maximum
      pharmacodynamic due to their physicochemical properties, poor stability,
      permeability and biodistribution. Despite the fact that the parenteral route
      remains the primary route of protein administration, research continues on non
      parenteral delivery routes. However, the high molecular weight of proteins,
      combined with their hydrophilic and charged nature, renders transport through
      membranes very difficult. In this regard, the biopolymer chitosan exhibits
      several favorable biological properties, such as biocompatibility,
      biodegradability, low-toxicity and mucoadhesiveness, which made it a promising
      candidate for the formulation of protein drugs. The success of a protein
      formulation depends not only on the stability of the delivery system but also on
      their ability to maintain the native structure and activity of the protein during
      preparation and the delivery, as well as during long-term storage of the
      formulation. Chitosan-based delivery systems have been proposed as valid
      approaches to provide such protective conditions. The development of novel
      protein delivery systems based on chitosan is a rising subject irrespective of
      the intended route of administration. In this review, the different approaches
      recently exploited to formulate and deliver therapeutic proteins are underlined.

PMID- 21091433
TI  - X-ray crystallographic snapshots of reaction intermediates in the G117H mutant of
      human butyrylcholinesterase, a nerve agent target engineered into a catalytic
      bioscavenger.
AB  - OPs (organophosphylates) exert their acute toxicity through inhibition of
      acetylcholinesterase, by phosphylation of the catalytic serine residue.
      Engineering of human butyrylcholinesterase, by substitution of a histidine
      residue for the glycine residue at position 117, led to the creation of OP
      hydrolase activity. However, the lack of structural information and poor
      understanding of the hydrolytic mechanism of the G117H mutant has hampered
      further improvements in the catalytic activity. We have solved the
      crystallographic structure of the G117H mutant with a variety of ligands in its
      active site. A sulfate anion bound to the active site suggested the positioning
      for an OP prior to phosphylation. A fluoride anion was found in the active site
      when NaF was added to the crystallization buffer. In the fluoride complex, the
      imidazole ring from the His117 residue was substantially shifted, adopting a
      relaxed conformation probably close to that of the unliganded mutant enzyme.
      Additional X-ray structures were obtained from the transient covalent adducts
      formed upon reaction of the G117H mutant with the OPs echothiophate and VX [ethyl
      ({2-[bis(propan-2-yl)amino]ethyl}sulfanyl](methyl)phosphinate]. The position of
      the His117 residue shifted in response to the introduction of these adducts,
      overlaying the phosphylserine residue. These structural data suggest that the
      dephosphylation mechanism involves either a substantial conformational change of
      the His117 residue or an adjacent nucleophilic substitution by water.

PMID- 21091435
TI  - The endoplasmic reticulum sulfhydryl oxidase Ero1beta drives efficient oxidative
      protein folding with loose regulation.
AB  - In eukaryotes, disulfide bonds are formed in the endoplasmic reticulum,
      facilitated by the Ero1 (endoplasmic reticulum oxidoreductin 1) oxidase/PDI
      (protein disulfide-isomerase) system. Mammals have two ERO1 genes, encoding
      Ero1alpha and Ero1beta proteins. Ero1beta is constitutively expressed in
      professional secretory tissues and induced during the unfolded protein response.
      In the present work, we show that recombinant human Ero1beta is twice as active
      as Ero1alpha in enzymatic assays. Ero1beta oxidizes PDI more efficiently than
      other PDI family members and drives oxidative protein folding preferentially via
      the active site in the a domain of PDI. Our results reveal that Ero1beta oxidase
      activity is regulated by long-range disulfide bonds and that Cys130 plays a
      critical role in feedback regulation. Compared with Ero1alpha, however, Ero1beta
      is loosely regulated, consistent with its role as a more active oxidase when
      massive oxidative power is required.

PMID- 21091424
TI  - The retinal pigment epithelium in health and disease.
AB  - Retinal pigment epithelial cells (RPE) constitute a simple layer of cuboidal
      cells that are strategically situated behind the photoreceptor (PR) cells. The
      inconspicuousness of this monolayer contrasts sharply with its importance [1].
      The relationship between the RPE and PR cells is crucial to sight; this is
      evident from basic and clinical studies demonstrating that primary dysfunctioning
      of the RPE can result in visual cell death and blindness. RPE cells carry out
      many functions including the conversion and storage of retinoid, the phagocytosis
      of shed PR outer segment membrane, the absorption of scattered light, ion and
      fluid transport and RPE-PR apposition. The magnitude of the demands imposed on
      this single layer of cells in order to execute these tasks, will become apparent
      to the reader of this review as will the number of clinical disorders that take
      origin from these cells.

PMID- 21091434
TI  - Substance P immunoreactive nerve fibres are related to gastric cancer
      differentiation status and could promote proliferation and migration of gastric
      cancer cells.
AB  - Tachykinins such as SP (substance P) may be involved in the progression of
      gastric adenocarcinoma through binding to NK-1 receptor. However, the existence
      and relationship between SP and gastric cancer progression and differentiation
      remained unknown. We have studied the NK-1 receptor in human gastric cancer
      tissue and MKN45 cell line and found SP-containing nerve fibres in human gastric
      cancer and found that the amounts of SP-positive nerves were related to gastric
      cancer differentiation. SP could promote proliferation, adhesion, migration and
      invasion of MKN45 cells in vitro. In addition, the intracellular calcium level of
      MKN45 cells was elevated after SP stimulation, and administration of CRACs
      (calcium release-activated calcium channels) inhibitor SKF-96365 could partially
      abolish these effects induced by SP. These results demonstrated that NK-1
      receptor and SP-containing nerves existed in human gastric cancer; SP positive
      nerves may play an important role in human gastric cancer progression, and
      calcium is critically significant among SP-induced biological effects.

PMID- 21091432
TI  - Angiotensin-(1-7) infusion is associated with increased blood pressure and
      adverse cardiac remodelling in rats with subtotal nephrectomy.
AB  - ACE (angiotensin-converting enzyme) 2 is expressed in the heart and kidney and
      metabolizes Ang (angiotensin) II to Ang-(1-7) a peptide that acts via the Ang-(1
      7) or mas receptor. The aim of the present study was to assess the effect of Ang
      (1-7) on blood pressure and cardiac remodelling in a rat model of renal mass
      ablation. Male SD (Sprague-Dawley) rats underwent STNx (subtotal nephrectomy) and
      were treated for 10 days with vehicle, the ACE inhibitor ramipril (oral 1 mg.kg(
      1) of body weight.day(-1)) or Ang-(1-7) (subcutaneous 24 MUg.kg(-1) of body
      weight.h(-1)) (all n = 15 per group). A control group (n = 10) of sham-operated
      rats were also studied. STNx rats were hypertensive (P<0.01) with renal
      impairment (P<0.001), cardiac hypertrophy (P<0.001) and fibrosis (P<0.05), and
      increased cardiac ACE (P<0.001) and ACE2 activity (P<0.05). Ramipril reduced
      blood pressure (P<0.01), improved cardiac hypertrophy (P<0.001) and inhibited
      cardiac ACE (P<0.001). By contrast, Ang-(1-7) infusion in STNx was associated
      with further increases in blood pressure (P<0.05), cardiac hypertrophy (P<0.05)
      and fibrosis (P<0.01). Ang-(1-7) infusion also increased cardiac ACE activity
      (P<0.001) and reduced cardiac ACE2 activity (P<0.05) compared with STNx-vehicle
      rats. Our results add to the increasing evidence that Ang-(1-7) may have
      deleterious cardiovascular effects in kidney failure and highlight the need for
      further in vivo studies of the ACE2/Ang-(1-7)/mas receptor axis in kidney
      disease.

PMID- 21091436
TI  - Flexibility of the Ure2 prion domain is important for amyloid fibril formation.
AB  - Ure2, the protein determinant of the Saccharomyces cerevisiae prion [URE3], has a
      natively disordered N-terminal domain that is important for prion formation in
      vivo and amyloid formation in vitro; the globular C-domain has a glutathione
      transferase-like fold. In the present study, we swapped the position of the N-
      and C-terminal regions, with or without an intervening peptide linker, to create
      the Ure2 variants CLN-Ure2 and CN-Ure2 respectively. The native structural
      content and stability of the variants were the same as wild-type Ure2, as
      indicated by enzymatic activity, far-UV CD analysis and equilibrium denaturation.
      CLN-Ure2 was able to form amyloid-like fibrils, but with a significantly longer
      lag time than wild-type Ure2; and the two proteins were unable to cross-seed.
      Under the same conditions, CN-Ure2 showed limited ability to form fibrils, but
      this was improved after addition of 0.03 M guanidinium chloride. As for wild-type
      Ure2, allosteric enzyme activity was observed in fibrils of CLN-Ure2 and CN-Ure2,
      consistent with retention of the native-like dimeric structure of the C-domains
      within the fibrils. Proteolytically digested fibrils of CLN-Ure2 and CN-Ure2
      showed the same residual fibril core morphology as wild-type Ure2. The results
      suggest that the position of the prion domain affects the ability of Ure2 to form
      fibrils primarily due to effects on its flexibility.

PMID- 21091438
TI  - Galectin-8 tandem-repeat structure is essential for T-cell proliferation but not
      for co-stimulation.
AB  - Gal (galectin)-8 is a tandem-repeat Gal containing N-CRDs (Nterminal carbohydrate
      recognition domains) and C-CRDs (C-terminal carbohydrate-recognition domains)
      with differential glycan-binding specificity fused by a linker peptide. Gal-8 has
      two distinct effects on CD4 T-cells: at high concentrations it induces antigen
      independent proliferation, whereas at low concentrations it co-stimulates antigen
      specific responses. Associated Gal-8 structural requirements were dissected in
      the present study. Recombinant homodimers N-N (two N-terminal CRD chimaera) and C
      C (two C-terminal CRD chimaera), but not single C-CRDs or N-CRDs, induced
      proliferation; however, single domains induced co-stimulation. These results
      indicate that the tandem-repeat structure was essential only for the
      proliferative effect, suggesting the involvement of lattice formation, whereas co
      stimulation could be mediated by agonistic interactions. In both cases, C-C
      chimaeras displayed higher activity than Gal-8, indicating that the C-CRD was
      mainly involved, as was further supported by the strong inhibition of
      proliferation and co-stimulation in the presence of blood group B antigen,
      specifically recognized by this domain. Classic Gal inhibitors (lactose and
      thiodigalactoside) prevented proliferation but not co-stimulatory activity, which
      was inhibited by 3-O-beta-D-galactopyranosyl-D-arabinose. Interestingly, Gal-8
      induced proliferation of naive human CD4 T-cells, varying from non- to high
      responder individuals, whereas it promoted cell death of phytohaemagglutinin or
      CD3/CD28 pre-activated cells. The findings of the present study delineate the
      differential molecular requirements for Gal-8 activities on T-cells, and suggest
      a dual activity relying on activation state.

PMID- 21091437
TI  - CDC25B associates with a centrin 2-containing complex and is involved in
      maintaining centrosome integrity.
AB  - BACKGROUND INFORMATION: CDC25 (cell division cycle 25) phosphatases function as
      activators of CDK (cyclin-dependent kinase)-cyclin complexes to regulate
      progression through the CDC. We have recently identified a pool of CDC25B at the
      centrosome of interphase cells that plays a role in regulating centrosome
      numbers. RESULTS: In the present study, we demonstrate that CDC25B forms a close
      association with Ctn (centrin) proteins at the centrosome. This interaction
      involves both N- and C-terminal regions of CDC25B and requires CDC25B binding to
      its CDK-cyclin substrates. However, the interaction is not dependent on the
      enzyme activity of CDC25B. Although CDC25B appears to bind indirectly to Ctn2,
      this association is pertinent to CDC25B localization at the centrosome. We
      further demonstrate that CDC25B plays a role in maintaining the overall integrity
      of the centrosome, by regulating the centrosome levels of multiple centrosome
      proteins, including that of Ctn2. CONCLUSIONS: Our results therefore suggest that
      CDC25B associates with a Ctn2-containing multiprotein complex in the cytoplasm,
      which targets it to the centrosome, where it plays a role in maintaining the
      centrosome levels of Ctn2 and a number of other centrosome components.

PMID- 21091439
TI  - Gelatin induces trophectoderm differentiation of mouse embryonic stem cells.
AB  - In this study, we selected gelatin as ECM (extracellular matrix) to support
      differentiation of mES (mouse embryonic stem) cells into TE (trophectoderm), as
      gelatin was less expensive and widely used. We found that 0.2% and 1.5% gelatin
      were the suitable concentrations to induce TE differentiation by means of
      detecting Cdx2 expression using real-time PCR. Moreover, about 15% cells were
      positive for Cdx2 staining after 6 days differentiation. We discovered that the
      expressions of specific markers for TE, such as Cdx2, Eomes, Hand1 and Esx1 were
      prominently increased after gelatin induction. Meanwhile, the expression of Oct4
      was significantly decreased. We also found that inhibition of the BMP (bone
      morphogenetic protein) signalling by Noggin could promote mES cells
      differentiation into TE, whereas inhibition of the Wnt signalling by Dkk1 had the
      contrary effect. This could be used as a tool to study the differentiation and
      function of early trophoblasts as well as further elucidating the molecular
      mechanism during abnormal placental development.

PMID- 21091440
TI  - Retinoic acid induces myoblasts transdifferentiation into premeiotic Stra8
      positive cells.
AB  - Spermatogonia and sperm-like cells can be derived in vitro via the addition of RA
      (retinoic acid) to pluripotent ES and EG cells. At present, however, these cells
      have not been derived from unipotent cells. Here, we have generated premeiotic
      Stra8-positive cells from C2C12 myoblasts following treatment with 10 MUM all
      trans-RA for 8 days. The differentiated C2C12 cells exhibited spherical
      morphology similar to spermatogonia, and they expressed gene markers of
      premeiosis, meiosis and postmeiosis. In addition, some of the transdifferentiated
      Stra8-positive cells had a tail-like phenotype. Flow cytometry results indicated
      that up to 20% of RA-induced C2C12 cells were Stra8-positive. Mvh (mouse vasa
      homologue) protein, a germ cell-specific ATP-dependent RNA helicase and Prm1
      (protamine 1) were detected in transdifferentiated cells. The DNA content in
      induced C2C12 cells showed that Stra8-positive cells were diploid, suggesting
      that the myoblast transdifferentiation was in the premeiotic stage of
      spermatogenesis. The derivation of Stra8-positive cells from C2C12 myoblasts has
      important implications for studying unipotent cell differentiation. Furthermore,
      C2C12 myoblasts may provide a useful in vitro cell model to study signal
      transduction and transdifferentiation during RA treatments.

PMID- 21091441
TI  - Chromatin regulation landscape of embryonic stem cell identity.
AB  - ES cells (embryonic stem cells) derived from the ICM (inner cell mass) of
      blastocysts are pluripotent and are capable of giving rise to most cell types.
      The ES cell identity is mainly maintained by the Oct4 (octamer-binding
      transcription factor 4) and Nanog transcriptional networks. Recently, a
      tremendous amount of work has focused on deciphering how ES cell identity is
      regulated epigenetically. It has been shown that histone
      methylation/demethylation, histone acetylation/deacetylation, histone variants
      and chromatin remodelling play crucial roles in ES cell maintenance and
      differentiation. Moreover, perturbation of those chromatin regulators results in
      loss of ES cell identity or aberrant differentiation. Therefore, it is important
      to fully understand the chromatin regulation landscape of ES cells. The knowledge
      gained will help us to harness the unique characteristics of ES cells for stem
      cell-related therapy and regenerative medicine. In the present review, we will
      discuss recent proceedings that provide novel insights into chromatin regulation
      of ES cell identity.

PMID- 21091442
TI  - Sphingosine kinase and sphingosine 1-phosphate in asthma.
AB  - Sphingolipids are amphiphatic molecules ubiquitously expressed in all eukaryotic
      cell membranes. Initially characterized as structural components of cell
      membranes, sphingolipids have emerged as sources of important signalling
      molecules over the past decade. Sphingolipid metabolites, such as ceramide and
      S1P (sphingosine 1-phosphate), have been demonstrated to have roles as potent
      bioactive messengers involved in cell differentiation, proliferation, apoptosis,
      migration and angiogenesis. The importance of SphK (sphingosine kinase) and S1P
      in inflammation has been demonstrated extensively. The prevalence of asthma is
      increasing in many developed nations. Consequently, there is an urgent need for
      the development of new agents for the treatment of asthma, especially for
      patients who respond poorly to conventional therapy. Recent studies have
      demonstrated the important role of SphK and S1P in the development of asthma by
      regulating pro-inflammatory responses. These novel pathways represent exciting
      potential therapeutic targets in the treatment of asthma and are described in the
      present review.

PMID- 21091443
TI  - Chemoattraction to lysophosphatidic acid does not require a change in membrane
      potential in Tetrahymena thermophila.
AB  - LPA (lysophosphatidic acid), a known chemoattractant for many types of eukaryotic
      cells, is also a reliable chemoattractant for Tetrahymena. Since LPA receptors
      are GPCRs (G-protein coupled receptors) in many cell types and several putative
      GPCR sequences can be found in the Tetrahymena Genome Database, we are interested
      to determine whether similar GPCR pathways can be used for chemosensory
      transduction in Tetrahymena. To confirm our procedures, we tested the known
      chemoattractant proteose peptone (at 1.0 mg/ml), which caused hyperpolarization
      and increased forward swimming speed in Tetrahymena, consistent with the current
      model for ciliate chemoattraction. Although 10 uM LPA did not produce these same
      responses, it was still an effective chemoattractant. PTX (pertussis toxin)
      blocked attraction to both of these compounds, suggesting a possible G-protein
      involvement in chemoattraction. Both of these chemoattractants also decreased the
      basal percent of cells showing direction changes [PDC (percent directional
      change)] and the duration of backward swimming in 0.5 mM Ba2+ (a general
      excitability assay). LPA probably causes chemoattraction in Tetrahymena by
      decreasing the basal PDC without changing either membrane potential or swim
      speed. Since a pertussis-sensitive G-protein might modulate the ciliate voltage
      dependent Ca2+ channels, we propose that LPA acts through an uncharacterized GPCR
      to lower the PDC by decreasing cellular excitability. These combined behavioural
      and electrophysiological analyses support the novel hypothesis that
      chemoattraction to some attractants, like LPA, can occur without
      hyperpolarization and increased swim speed in Tetrahymena.

PMID- 21091444
TI  - An improved bimolecular fluorescence complementation assay with a high signal-to
      noise ratio.
AB  - Protein-protein interactions (PPIs) play crucial roles in various biological
      processes. Among biochemical, genetic, and imaging approaches that have been used
      for the study of PPIs, visualization of PPIs in living cells is the key to
      understanding their cellular functions. The bimolecular fluorescence
      complementation (BiFC) assay represents one of these imaging tools for direct
      visualization of PPIs in living cells. The BiFC assay is based on the structural
      complementation of two nonfluorescent N- and C-terminal fragments of a
      fluorescent protein when they are fused to a pair of interacting proteins.
      Although over 10 different fluorescent proteins have been used for BiFC assays,
      the two nonfluorescent fragments from all of these fluorescent proteins can
      spontaneously self-assemble, which contributes to background fluorescence and
      decreases the signal-to-noise (S/N) ratio in the BiFC assay. Here we report the
      identification of a mutation, I152L, that can specifically reduce self-assembly
      and decrease background fluorescence in a Venus-based BiFC system. This mutation
      allows a 4-fold increase in the S/N ratio of the BiFC assay in living cells. This
      improved Venus-based BiFC system will facilitate PPI studies in various
      biological research fields.

PMID- 21091446
TI  - A ligation-independent cloning method using nicking DNA endonuclease.
AB  - Using nicking DNA endonuclease (NiDE), we developed a novel technique to clone
      DNA fragments into plasmids. We created a NiDE cassette consisting of two
      inverted NiDE substrate sites sandwiching an asymmetric four-base sequence, and
      NiDE cleavage resulted in 14-base single-stranded termini at both ends of the
      vector and insert. This method can therefore be used as a ligation-independent
      cloning strategy to generate recombinant constructs rapidly. In addition, we
      designed and constructed a simple and specific vector from an Escherichia coli
      plasmid back-bone to complement this cloning method. By cloning cDNAs into this
      modified vector, we confirmed the predicted feasibility and applicability of this
      cloning method.

PMID- 21091445
TI  - Four-color single-molecule fluorescence with noncovalent dye labeling to monitor
      dynamic multimolecular complexes.
AB  - To enable studies of conformational changes within multimolecular complexes, we
      present a simultaneous, four-color single molecule fluorescence methodology
      implemented with total internal reflection illumination and camera-based, wide
      field detection. We further demonstrate labeling histidine-tagged proteins
      noncovalently with Tris-nitrilotriacetic acid (Tris-NTA)-conjugated dyes to
      achieve single molecule detection. We combine these methods to colocalize the
      mismatch repair protein MutSalpha on DNA while monitoring MutSalpha-induced DNA
      bending using Forster resonance energy transfer (FRET) and to monitor assembly of
      membrane-tethered SNARE protein complexes.

PMID- 21091448
TI  - A bacterial two-hybrid system that utilizes Gateway cloning for rapid screening
      of protein-protein interactions.
AB  - Comprehensive clone sets representing the entire genome now exist for a large
      number of organisms. The Gateway entry clone sets are a particularly useful means
      to study gene function, given the ease of introduction into any Gateway-suitable
      destination vector. We have adapted a bacterial two-hybrid system for use with
      Gateway entry clone sets, such that potential interactions between proteins
      encoded within these clone sets can be determined by new destination vectors. We
      show that utilizing the Gateway clone sets for Francisella tularensis and Vibrio
      cholerae, known interactions between F. tularensis IglA and IglB and V. cholerae
      VipA and VipB could be confirmed with these destination vectors. Moreover, the
      introduction of unique tags into each vector allowed for visualization of the
      expressed hybrid proteins via Western immunoblot. This Gateway-suitable bacterial
      two-hybrid system provides a new tool for rapid screening of protein-protein
      interactions.

PMID- 21091447
TI  - An efficient and information-rich biochemical method design for fragment library
      screening on ion channels.
AB  - Drug discovery requires a simple, rapid, and cost-effective method for the early
      identification of novel leads and elimination of poor candidates. Here we present
      an experimental design that fulfils these criteria, using a ligand-gated ion
      channel expressed in a mammalian cell line, whose function can be probed using a
      voltage-sensitive dye. The experimental design is novel, as it uses the same
      screen to identify hit fragments and to characterize them as agonists or
      antagonists. The results were independently validated using radioligand binding,
      although the new technique has several advantages over radioligand methods. A
      number of novel high-affinity ligands were found. The method is broadly
      applicable to a wide range of receptor types including ligand-gated ion channels
      (LGICs), voltage-gated ion channels (VGICs), and G protein-coupled receptors
      (GPCRs), all of which are important drug targets.

PMID- 21091449
TI  - Standardized SSR allele naming and binning among projects.
AB  - Simple sequence repeats (SSRs) have proven to be extremely valuable DNA markers
      for genetic mapping and population genetic analyses. However, data collected
      across laboratories or even within laboratories are difficult to combine due to
      challenges in standardizing allele names, especially for nonmodel systems. Here
      we provide a new approach for standardizing SSR allele names that combines
      several previously recognized components for standardization, including reference
      samples/alleles, cumulative binsets, static between-allele spacing, and interval
      allele naming.

PMID- 21091450
TI  - Effects of freezing and protein cross-linker on isolating membrane raft
      associated proteins.
AB  - Since the discovery of cellular membrane rafts, the defining of these domains has
      remained ambiguous due to a great number of isolation procedures proposed for the
      extraction of the rafts from cells. Characterization of membrane rafts using
      Triton X-100 insolubility is limited by the fact that weak interactions between
      proteins and lipids within the membrane rafts cannot be detected. In order to
      study the role of membrane rafts in cell signal transduction, it is crucial that
      weak membrane raft-associated proteins are detected. In this report, we
      demonstrate that by incorporating 3,3'-dithiobis(sulfosuccinimidyl propionate)
      (DTSSP) crosslinking and freezing at -80 degrees C into the membrane raft
      isolation procedure of HaCaT cells, both membrane raft-associated proteins
      caveolin-1 and Fas receptor are able to be reproducibly isolated into a single
      fraction containing the membrane rafts of the cells.

PMID- 21091451
TI  - An alternative model for quantitative trait loci (QTL) analysis in general
      pedigrees.
AB  - Linkage detection of a trait involves detecting regions of the genome that
      influence the trait. A wide variety of statistical models are currently employed
      for linkage analysis of quantitative traits. Many of these models are developed
      under some assumptions of the trait distributions. Violation of the assumptions
      about the trait generally affects the type I error and power for linkage
      detection. In this paper, we have proposed a trait-model-free approach for
      linkage analysis of a quantitative trait in general pedigrees. The conditional
      segregation of marker alleles given the trait is modeled using a latent-variable
      logistic model. A likelihood-ratio test is used to test for linkage under our
      model. The main applicability of this approach lies in the fact that it always
      provides correct type I error no matter what the trait distribution is and thus
      can be used for nonnormal traits or for selected samples. By means of simulation
      studies, we have compared the power of our proposed model with existing
      approaches for nonnormal traits. The performance of these methods was also
      studied on a real dataset. We have demonstrated the usefulness of our approach in
      terms of power and robustness for linkage detection of quantitative traits in
      general pedigrees.

PMID- 21091452
TI  - Diachronic investigations of mitochondrial and Y-chromosomal genetic markers in
      pre-Columbian Andean highlanders from South Peru.
AB  - This study examines the reciprocal effects of cultural evolution, and population
      dynamics in pre-Columbian southern Peru by the analysis of DNA from pre-Columbian
      populations that lived in the fringe area between the Andean highlands and the
      Pacific coast. The main objective is to reveal whether the transition from the
      Middle Horizon (MH: 650-1000 AD) to the Late Intermediate Period (LIP: 1000-1400
      AD) was accompanied or influenced by population dynamic processes. Tooth samples
      from 90 individuals from several archaeological sites, dating to the MH and LIP,
      in the research area were collected to analyse mitochodrial, and Y-chromosomal
      genetic markers. Coding region polymorphisms were successfully analysed and
      replicated for 72 individuals, as were control region sequences for 65
      individuals and Y-chromosomal single nucleotide polymorphisms (SNPs) for 19
      individuals, and these were compared to a large set of ancient and modern
      indigenous South American populations. The diachronic comparison of the upper
      valley samples from both time periods reveals no genetic discontinuities
      accompanying the cultural dynamic processes. A high genetic affinity for other
      ancient and modern highland populations can be observed, suggesting genetic
      continuity in the Andean highlands at the latest from the MH. A significant
      matrilineal differentiation to ancient Peruvian coastal populations can be
      observed suggesting a differential population history.

PMID- 21091453
TI  - Bayesian models for detecting epistatic interactions from genetic data.
AB  - Current disease association studies are routinely conducted on a genome-wide
      scale, testing hundreds of thousands or millions of genetic markers. Besides
      detecting marginal associations of individual markers with the disease, it is
      also of interest to identify gene-gene and gene-environment interactions, which
      confer susceptibility to the disease risk. The astronomical number of possible
      combinations of markers and environmental factors, however, makes interaction
      mapping a daunting task both computationally and statistically. In this paper, we
      review and discuss a set of Bayesian partition methods developed recently for
      mapping single-nucleotide polymorphisms in case-control studies, their extension
      to quantitative traits, and further generalization to multiple traits. We use
      simulation and real data sets to demonstrate the performance of these methods,
      and we compare them with some existing interaction mapping algorithms. With the
      recent advance in high-throughput sequencing technologies, genome-wide
      measurements of epigenetic factor enrichment, structural variations, and
      transcription activities become available at the individual level. The tsunami of
      data creates more challenges for gene-gene interaction mapping, but at the same
      time provides new opportunities that, if utilized properly through sophisticated
      statistical means, can improve the power of mapping interactions at the genome
      scale.

PMID- 21091454
TI  - Deadly cattle disease will soon be history.

PMID- 21091456
TI  - Prevalence of Cysticercus bovis (beef measles) in Australian cattle.

PMID- 21091457
TI  - A survey of aged horses in Queensland, Australia. Part 2: Clinical signs and
      owners' perceptions of health and welfare.
AB  - OBJECTIVE: To describe the prevalence and risk factors for clinical signs of
      disease and owner-reported health or welfare issues of aged horses in Queensland,
      Australia. METHODS: Owners of horses were contacted via an equestrian
      organisation in Queensland and asked to complete a questionnaire about their
      horses aged 15 years and older, to gain information about clinical signs observed
      in the horse and disease history. Owners were asked to identify health or welfare
      issues they felt were important in aged horses. RESULTS: Owners were able to
      identify many clinical signs of disease, with 83% of horses having at least one
      reported clinical sign of disease. Muscle stiffness (33%), lameness (28%), ocular
      discharge (22%), change in hair coat (22%) and skin problems (21%) were the most
      commonly reported signs. Increasing age was a risk factor for the presence of
      clinical signs of disease. Ponies had an increased risk of both laminitis and
      hirsutism, whereas Thoroughbreds had an increased risk of stereotypies, wounds,
      weight loss and musculoskeletal signs. Owners reported a known disease or
      disorder in their horses less frequently than the clinical signs of disease.
      Owners reported weight loss (28%), arthritis/lameness (24%) and teeth/dental care
      (18%) as the most important health issues, followed by welfare issues (8%).
      CONCLUSION: Owners demonstrated concern for the health and welfare of their aged
      horses, but the lack of appropriate recognition of the significance of clinical
      signs and limited veterinary care suggest a need for increased client
      communication and veterinarian-client interaction.

PMID- 21091458
TI  - Use of pressor therapy in 34 hypotensive critically ill neonatal foals.
AB  - BACKGROUND: Arginine vasopressin (AVP) is used in human medicine in the
      management of vasodilatory shock and cardiac arrest, but it is not widely used in
      equine neonatal intensive care because of concerns about potential side effects
      and suboptimal efficacy. This retrospective study reports the clinical use of AVP
      and norepinephrine (NE) in foals with refractory hypotension. OBJECTIVES: To
      report the cardiovascular responses and fluid balance in critically ill,
      hypotensive foals receiving either NE or AVP. DESIGN: The medical records of
      neonatal foals (<7 days of age) from 2000 to 2007 admitted to the Marion duPont
      Scott Equine Medical Center were reviewed. RESULTS: The use of exogenous AVP
      infusion was associated with a significant increase in mean arterial pressure
      (MAP) and urinary output, and a significant decrease in heart rate. NE
      administration was also associated with a significant increase in MAP.
      CONCLUSIONS: The findings of this first report of the clinical treatment of foals
      with refractory hypotension support the use of AVP and NE.

PMID- 21091459
TI  - Fluoroscopic stent placement for the relief of malignant urethral obstruction in
      a cat.
AB  - The clinical features and interventional therapy in the case of a female cat with
      urinary tract obstruction secondary to neoplasia are presented. This form of
      neoplasia in cats is rare and therapeutic intervention to relieve urinary tract
      obstruction caused by malignancy has been described only once. This is the first
      report of a self-expandable metallic stent placed in a feline urethra to relieve
      obstruction caused by malignancy and the first report of the use of a unique
      composite metallic stent (PlatinolTM) in a cat. In conclusion, the palliative
      stenting of the feline urethra may be a valid therapeutic intervention for
      malignancies. Further studies are required to determine the optimal size and type
      of stent that will provide the greatest benefit.

PMID- 21091460
TI  - Physiological and behavioural effects of intradermal injection of sodium lauryl
      sulfate as an alternative to mulesing in lambs.
AB  - OBJECTIVE: To assess the effects on physiology and behaviour of intradermal
      injection of sodium lauryl sulfate (SLS) as an alternative to mulesing.
      PROCEDURES: Three groups of Merino lambs were studied: Control (n = 10), SLS (n =
      11) and Mulesed (n = 11). The SLS group received SLS (7% w/v) and benzyl alcohol
      (20 mg/mL) in phosphate buffer, and the Mulesed group received 6 mL topical local
      anaesthetic as a wound dressing. Haematology, cortisol, beta-endorphin and
      haptoglobin concentrations, rectal temperatures, body weight and behaviours were
      monitored for up to 42 days post treatments. RESULTS: SLS treatment induced mild
      swelling followed by thin scab formation. Fever (>40 degrees C) was observed at
      12 and 24 h, cortisol concentration was elevated on days 1 and 2, haptoglobin
      concentration was highly elevated on days 2-7, white blood cell count was
      elevated on days 2 and 4 post treatment, but average daily gain was not affected.
      Fever at 12 h was significantly higher in the SLS than in the Mulesed group,
      whereas maximum temperature, temperature area under the curve (AUC), occurrence
      of fever, cortisol profile, cortisol AUC, white blood cell counts and haptoglobin
      concentrations until day 7 were comparable. The behaviours of normal standing,
      total standing and total lying were modified for 2 days by SLS treatment, but
      changes were less marked and of shorter duration than in the Mulesed group. On
      day 1, the SLS group spent <5% of time in total abnormal behaviours compared with
      18% in the Mulesed group. The SLS group tended to spend more time in abnormal
      behaviours on day 1 than the Controls. CONCLUSIONS: The behaviour of the SLS
      group was similar to that of the unmulesed Controls and their physiological
      responses were intermediate between the Mulesed lambs receiving post-surgical
      analgesia and the Controls.

PMID- 21091461
TI  - Assessment of risk of monepantel faecal residues to dung fauna.
AB  - OBJECTIVE: To evaluate the safety of monepantel and its major metabolite for dung
      fauna. Monepantel is a new oral anthelmintic drug for use in sheep at a dose of
      2.5 mg active ingredient/kg body weight. Hazard (toxicity) is related to the
      expected exposure. DESIGN: The methodology was based on the Organisation for
      Economic Cooperation and Development (OECD) draft guideline for testing of
      chemicals, so dung from cattle, not sheep, and eggs of the dung fly, Scathophaga
      stercoraria and larvae of the dung beetle Aphodius constans were used.
      PROCEDURES: Monepantel or its sulfone metabolite were mixed into bovine faeces in
      which either dung fly eggs or dung beetle larvae were placed and their
      development observed. The primary endpoint was survival. Real exposure data
      (faecal concentrations) for comparison with the generated laboratory data were
      taken from a kinetics study in sheep dung. RESULTS: The no-observed effect
      concentration (NOEC) for monepantel was >1000 mg/kg substrate for dung flies and
      250 mg/kg for dung beetles. The sulfone metabolite was slightly more toxic, with
      a NOEC of 500 mg/kg for dung flies and 125 mg/kg for dung beetles. CONCLUSION: A
      comparison of the results to the maximum concentrations of 15 mg monepantel and
      4.5 mg sulfone per kg dung observed under an exaggerated dosing regime in sheep
      indicates that monepantel poses no risk to insect dung fauna when used as
      recommended. The study is considered valid because representatives of both genera
      were able to develop in bovine or ovine dung.

PMID- 21091462
TI  - Morbidity, mortality and body weight gain of surgically spayed, yearling Brahman
      heifers.
AB  - OBJECTIVE: To determine morbidity and mortality rates in yearling heifers spayed
      by two methods under commercial conditions in northern Australia. DESIGN: In
      study 1,600 Brahman heifers were allocated to one of three treatments: physical
      restraint and ear-tagging (Control); physical restraint, ovariectomy by the
      Willis dropped ovary technique, ear-tagging and ear-marking (WDOT); or
      electroimmobilisation, ovariectomy via flank incision, ear-tagging and ear
      marking (Flank). Heifers were monitored post spaying. Mortalities occurred at
      unanticipated times, so study 2 investigated their timing and cause in similar
      WDOT-spayed heifers (n=574). RESULTS: In study 1, morbidity on the day of spaying
      was 6.0% in the Flank and 2.7% in the WDOT group (not statistically different).
      Spayed heifers showed behaviours indicative of acute pain/discomfort in the 6 h
      post spaying. Body weights and gains were significantly lower in the spayed
      compared with control heifers at days 21 and 42, and 5% of flank wounds were not
      healed at day 42. Mortalities were 0%, 1.5% and 2.5%, respectively, for Control,
      WDOT (3 estimated to have occurred on day 11) and Flank (2 on the day after
      spaying and 1 on each of days 5, 11 and 22). In study 2, the mortality was 0.5%,
      all within 4 days of spaying. CONCLUSIONS: In yearling heifers, WDOT spaying
      resulted in lower morbidity and short-term mortality compared with flank spaying.
      Both methods compromised the health and welfare of some animals for up to 4 days
      and body weight gains were reduced during the 6 weeks post spaying.

PMID- 21091463
TI  - Anthelmintic resistance in cattle nematodes on 13 south-west Victorian
      properties.
AB  - OBJECTIVE: To report the level of anthelmintic resistance on 13 commercial cattle
      properties in south-west Victoria, Australia. PROCEDURE: Between 2006 and 2009
      worm egg count reduction tests were conducted on calves on the 13 properties.
      Samples were collected 10-14 days post anthelmintic treatment and worm egg counts
      and larval differentiation tests were conducted. Resistance was defined if there
      was less than 95% reduction (lower confidence limit <90%) in the faecal worm egg
      count for the particular genus. RESULTS: The percentage of properties with
      anthelmintic resistance in at least one species was 54% for benzimidazole (BZ),
      100% for levamisole (LEV) and for ivermectin (IVM) it was 100% for the half-dose
      (0.1 mg/kg) and 62% for the full dose (0.2 mg/kg). A substantial frequency of
      resistance was detected in Ostertagia ostertagi to BZ (5/11), LEV (3/3) and IVM
      (5/11), in Trichostrongylus spp. to BZ (4/7) and in Cooperia spp. to IVM (6/11).
      No resistance to LEV was detected in Trichostrongylus or Cooperia spp. Suspected
      IVM-resistant Trichostrongylus spp. and BZ-resistant Cooperia spp. were only
      detected on one property each. CONCLUSION: This is the first Australian report of
      macrocyclic lactone-resistant O. ostertagi in the refereed literature. The
      frequency of resistance in O. ostertagi to BZ, LEV and IVM and in
      Trichostrongylus spp. to BZ in the present study appears higher than levels
      detected in the 2004-05 New Zealand survey, whereas the resistance frequency in
      Cooperia spp. to IVM and BZ was less.

PMID- 21091464
TI  - Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual
      disability with or without autism.
AB  - Submicroscopic chromosomal anomalies play an important role in the aetiology of
      intellectual disability (ID) and have been shown to account for up to 10% of non
      syndromic forms. We present a family with two affected boys compatible with X
      linked inheritance of a phenotype of severe neurodevelopmental disorder co
      segregating with a deletion in Xp22.11 exclusively containing the PTCHD1 gene.
      Although the exact function of this gene is unknown to date, the structural
      overlap of its encoded patched domain-containing protein 1, the transmembrane
      protein involved in the sonic hedgehog pathway, and its expression in human
      cortex and cerebellum as well as in mice and drosophila brain suggests a
      causative role of its nullisomy in the developmental phenotype of our family. Our
      findings support the recent notions that PTCHD1 may play a role in X-linked
      intellectual disability (XLID) and autism disorders.

PMID- 21091465
TI  - Genetic variation and covariation in floral allocation of two species of Schiedea
      with contrasting levels of sexual dimorphism.
AB  - The evolution of sexual dimorphism depends in part on the additive genetic
      variance-covariance matrices within females, within males, and across the sexes.
      We investigated quantitative genetics of floral biomass allocation in females and
      hermaphrodites of gynodioecious Schiedea adamantis (Caryophyllaceae). The G
      matrices within females (G(f)), within hermaphrodites (G(m)), and between sexes
      (B) were compared to those for the closely related S. salicaria, which exhibits a
      lower frequency of females and less-pronounced sexual dimorphism. Additive
      genetic variation was detected in all measured traits in S. adamantis, with
      narrow-sense heritability from 0.34-1.0. Female allocation and floral size traits
      covaried more tightly than did those traits with allocation to stamens. Between
      sex genetic correlations were all <1, indicating sex-specific expression of
      genes. Common principal-components analysis detected differences between G(f) and
      G(m) , suggesting potential for further independent evolution of the sexes. The
      two species of Schiedea differed in G(m) and especially so in G(f) , with S.
      adamantis showing greater genetic variation in capsule mass and tighter genetic
      covariation between female allocation traits and flower size in females. Despite
      greater sexual dimorphism in S. adamantis, genetic correlations between the two
      sexes (standardized elements of B) were similar to correlations between sexes in
      S. salicaria.

PMID- 21091466
TI  - Sex reduces genetic variation: a multidisciplinary review.
AB  - For over a century, the paradigm has been that sex invariably increases genetic
      variation, despite many renowned biologists asserting that sex decreases most
      genetic variation. Sex is usually perceived as the source of additive genetic
      variance that drives eukaryotic evolution vis-a-vis adaptation and Fisher's
      fundamental theorem. However, evidence for sex decreasing genetic variation
      appears in ecology, paleontology, population genetics, and cancer biology. The
      common thread among many of these disciplines is that sex acts like a coarse
      filter, weeding out major changes, such as chromosomal rearrangements (that are
      almost always deleterious), but letting minor variation, such as changes at the
      nucleotide or gene level (that are often neutral), flow through the sexual sieve.
      Sex acts as a constraint on genomic and epigenetic variation, thereby limiting
      adaptive evolution. The diverse reasons for sex reducing genetic variation
      (especially at the genome level) and slowing down evolution may provide a
      sufficient benefit to offset the famed costs of sex.

PMID- 21091467
TI  - A strategy to increase cooperation in the volunteer's dilemma: reducing vigilance
      improves alarm calls.
AB  - One of the most common examples of cooperation in animal societies is giving the
      alarm in the presence of a predator. A reduction in individual vigilance against
      predators when group size increases (the "group size effect") is one of the most
      frequently reported relationships in the study of animal behavior, and is thought
      to be due to relaxed selection, either because more individuals can detect the
      predator more easily (the "many eyes" effect) or because the risk of predator
      attack is diluted on more individuals (the "selfish herd" effect). I show that
      these hypotheses are not theoretically grounded: because everybody relies on
      someone else to raise the alarm, the probability that at least one raises the
      alarm declines with group size; therefore increasing group size does not lead to
      relaxed selection. Game theory shows, instead, that increasing the risk that the
      predator is not reported (by reducing vigilance) induces everybody to give the
      alarm more often. The group size effect, therefore, can be due to strategic
      behavior to improve the production of a public good. This shows how a selfish
      behavior can lead to a benefit for the group, and suggests a way to solve social
      dilemmas in the absence of relatedness and repeated interactions.

PMID- 21091468
TI  - Power and corruption.
AB  - Cooperation is ubiquitous in the natural world. What seems nonsensical is why
      natural selection favors a behavior whereby individuals would lose out by
      benefiting their competitor. This conundrum, for almost half a century, has
      puzzled scientists and remains a fundamental problem in biology, psychology, and
      economics. In recent years, the explanation that punishment can maintain
      cooperation has received much attention. Individuals who punish noncooperators
      thrive when punishment does not entail a cost to the punisher. However when
      punishment is costly, cooperation cannot be preserved. Most literature on
      punishment fails to consider that punishers may act corruptly by not cooperating
      when punishing noncooperators. No research has considered that there might be
      power asymmetries between punishers and nonpunishers that turn one of these type
      of individuals more or less susceptible to experiencing punishment. Here, we
      formulate a general game allowing corruption and power asymmetries between
      punishers and nonpunishers. We show that cooperation can persist if punishers
      possess power and use it to act corruptly. This result provides a new
      interpretation of recent data on corrupt policing in social insects and the
      psychology of power and hypocrisy in humans. These results suggest that
      corruption may play an important role in maintaining cooperation in insects and
      human societies. In contrast with previous research, we contend that costly
      punishment can be beneficial for social groups. This work allows us to identify
      ways in which corruption can be used to the advantage of a society.

PMID- 21091469
TI  - The effect of developmental temperature on the genetic architecture underlying
      size and thermal clines in Drosophila melanogaster and D. simulans from the east
      coast of Australia.
AB  - Body size and thermal tolerance clines in Drosophila melanogaster occur along the
      east coast of Australia. However the extent to which temperature affects the
      genetic architecture underlying the observed clinal divergence remains unknown.
      Clinal variation in these traits is associated with cosmopolitan chromosome
      inversions that cline in D. melanogaster. Whether this association influences the
      genetic architecture for these traits in D. melanogaster is unclear. Drosophila
      simulans shows linear clines in body size, but nonlinear clines in cold
      resistance. Clinally varying inversions are absent in D. simulans. Line-cross and
      clinal analyses were performed between tropical and temperate populations of D.
      melanogaster and D. simulans from the east coast of Australia to investigate
      whether clinal patterns and genetic effects contributing to clinal divergence in
      wing centroid size, thorax length, wing-to-thorax ratio, cold and heat resistance
      differed under different developmental temperatures (18  degrees C, 25  degrees
      C, and 29  degrees C). Developmental temperature influenced the genetic
      architecture in both species. Similarities between D. melanogaster and D.
      simulans suggest clinally varying inversion polymorphisms have little influence
      on the genetic architecture underlying clinal divergence in size in D.
      melanogaster. Differing genetic architectures across different temperatures
      highlight the need to consider different environments in future evolutionary and
      molecular studies of phenotypic divergence.

PMID- 21091470
TI  - Psychometric properties of the patient activation measure among multimorbid older
      adults.
AB  - OBJECTIVES: The Patient Activation Measure (PAM) quantifies the extent to which
      people are informed about and involved in their health care. Objectives were to
      determine the psychometric properties of PAM among multimorbid older adults and
      evaluate a theoretical, four-stage model of patient activation. Methods. A cross
      sectional analysis was used to assess the psychometric properties of PAM.
      Internal consistency was assessed using Cronbach alpha. Construct validity was
      evaluated using general linear modeling to compute associations between PAM
      scores and health-related behaviors, functional status, and health care quality.
      Latent class analysis was used to evaluate the theoretical four-stage structure
      of patient activation. STUDY SETTING: Participants in a randomized trial of
      Guided Care (N = 855), a model of comprehensive health care for older adults with
      chronic conditions that put them at risk of using health services heavily during
      the coming year. PRINCIPAL FINDINGS: Higher PAM activation scores and stage were
      positively associated with higher functional status, health care quality, and
      adherence to some health behaviors. Latent class analysis supported the
      multistage theory of patient activation. CONCLUSIONS: The PAM is a reliable,
      valid, and potentially clinically useful measure of patient activation for
      multimorbid older adults.

PMID- 21091471
TI  - The impacts of state health reform initiatives on adults in New York and
      Massachusetts.
AB  - OBJECTIVE: To analyze the effects of health reform efforts in two large states-
      New York and Massachusetts. DATA SOURCES/STUDY SETTING: National Health Interview
      Survey (NHIS) data from 1999 to 2008. STUDY DESIGN: We take advantage of the
      "natural experiments" that occurred in New York and Massachusetts to compare
      health insurance coverage and health care access and use for adults before and
      after the implementation of the health policy changes. To control for underlying
      trends not related to the reform initiatives, we subtract changes in the outcomes
      over the same time period for comparison groups of adults who were not affected
      by the policy changes using a differences-in-differences framework. The analyses
      are conducted using multiple comparison groups and different time periods as a
      check on the robustness of the findings. DATA COLLECTION/EXTRACTION METHODS:
      Nonelderly adults ages 19-64 in the NHIS. PRINCIPAL FINDINGS: We find evidence of
      the success of the initiatives in New York and Massachusetts at expanding
      insurance coverage, with the greatest gains reported by the initiative that was
      broadest in scope--the Massachusetts push toward universal coverage. There is no
      evidence of improvements in access to care in New York, reflecting the small
      gains in coverage under that state's reform effort and the narrow focus of the
      initiative. In contrast, there were significant gains in access to care in
      Massachusetts, where the impact on insurance coverage was greater and a more
      comprehensive set of reforms were implemented to improve access to a full array
      of health care services. The estimated gains in coverage and access to care
      reported here for Massachusetts were achieved in the early period under health
      reform, before the state's reform initiative was fully implemented. CONCLUSIONS:
      Comprehensive reform initiatives are more successful at addressing gaps in
      coverage and access to care than are narrower efforts, highlighting the potential
      gains under national health reform. Tracking the implications of national health
      reform will be challenging, as sample sizes and content in existing national
      surveys are not currently sufficient for in-depth evaluations of the impacts of
      reform within many states.

PMID- 21091472
TI  - Patient-centered care categorization of U.S. health care expenditures.
AB  - OBJECTIVE: To categorize national medical expenditures into patient-centered
      categories. DATA SOURCES: The 2007 Medical Expenditure Panel Survey (MEPS), a
      nationally representative annual survey of the civilian noninstitutionalized
      population. STUDY DESIGN: Descriptive statistics categorizing expenditures into
      seven patient-centered care categories: chronic conditions, acute illness,
      trauma/injury or poisoning, dental, pregnancy/birth-related, routine preventative
      health care, and other. DATA COLLECTION METHODS: MEPS cohort. PRINCIPAL FINDINGS:
      Nearly half of expenditures were for chronic conditions. The remaining
      expenditures were as follows: acute illness (25 percent), trauma/poisoning (8
      percent), dental (7 percent), routine preventative health care (6 percent),
      pregnancy/birth-related (4 percent), and other (3 percent). Hospital-based
      expenditures accounted for the majority for acute illness, trauma/injury, and
      pregnancy/birth and over a third for chronic conditions. CONCLUSIONS: This
      patient-centered viewpoint may complement other methods to examine health care
      expenditures and may better represent how patients interact with the health care
      system and expend resources.

PMID- 21091474
TI  - A simple cell based assay to measure Parkin activity.
AB  - Parkin is an ubiquitin-protein ligase mutated in Autosomal Recessive - Juvenile
      Parkinsonism. Here, we describe a cell-based assay to measure Parkin's ubiquitin
      protein ligase activity. It relies on the ability of Parkin to recognise
      depolarised mitochondria and exploits a cell line where Parkin expression is
      inducible. In these cells, Parkin expression promotes mitophagy and accelerates
      cell death in response to mitochondrial depolarisers. Time-lapse imaging
      confirmed cell death and revealed increased perinuclear mitochondrial clustering
      following induction of Parkin expression in cells exposed to carbonyl cyanide m
      chlorophenylhydrazone. Similar effects were not observed with alpha-synuclein or
      DJ-1, other proteins associated with the development of Parkinson's disease,
      confirming the specificity of the assay. We have used this assay to demonstrate
      that ligase-defective Parkin mutants are inactive, and cellular proteasomal
      activity (using the proteasomal inhibitors MG132, clasto-lactacystin beta-lactone
      and epoxomicin) is essential for the Parkin mediated effect. As the assay is
      suitable for high-throughput screening, it has the potential to identify novel
      proteostasis compounds that stimulate the activity of Parkin mutants for
      therapeutic purposes, to identify modulators of kinase activities that impact on
      Parkin function, and to act as a functional read-out in reverse genetics screens
      aimed at identifying modifiers of Parkin function during mitophagy.

PMID- 21091473
TI  - A neuroprotective role for angiogenin in models of Parkinson's disease.
AB  - We previously observed marked down-regulation of the mRNA for angiogenin, a
      potent inducer of neovascularization, in a mouse model of Parkinson's disease
      (PD) based on over-expression of alpha-synuclein. Angiogenin has also been
      recently implicated in the pathogenesis of amyotrophic lateral sclerosis. In this
      study, we confirmed that mouse angiogenin-1 protein is dramatically reduced in
      this transgenic alpha-synuclein mouse model of PD, and examined the effect of
      angiogenin in cellular models of PD. We found that endogenous angiogenin is
      present in two dopamine-producing neuroblastoma cell lines, SH-SY5Y and M17, and
      that exogenous angiogenin is taken up by these cells and leads to phosphorylation
      of Akt. Applied angiogenin protects against the cell death induced by the
      neurotoxins 1-methyl-4-phenylpyridinium and rotenone and reduces the activation
      of caspase 3. Together our data supports the importance of angiogenin in
      protecting against dopaminergic neuronal cell death and suggests its potential as
      a therapy for PD.

PMID- 21091475
TI  - Mammalian retinal horizontal cells are unconventional GABAergic neurons.
AB  - Lateral interactions at the first retinal synapse have been initially proposed to
      involve GABA by transporter-mediated release from horizontal cells, onto GABA(A)
      receptors expressed on cone photoreceptor terminals and/or bipolar cell
      dendrites. However, in the mammalian retina, horizontal cells do not seem to
      contain GABA systematically or to express membrane GABA transporters. We here
      report that mouse retinal horizontal cells express GAD65 and/or GAD67 mRNA, and
      were weakly but consistently immunostained for GAD65/67. While GABA was readily
      detected after intracardiac perfusion, it was lost during classical preparation
      for histology or electrophysiology. It could not be restored by incubation in a
      GABA-containing medium, confirming the absence of membrane GABA transporters in
      these cells. However, GABA was synthesized de novo from glutamate or glutamine,
      upon addition of pyridoxal 5'-phosphate, a cofactor of GAD65/67. Mouse horizontal
      cells are thus atypical GABAergic neurons, with no functional GABA uptake, but a
      glutamate and/or glutamine transport system allowing GABA synthesis, probably
      depending physiologically from glutamate released by photoreceptors. Our results
      suggest that the role of GABA in lateral inhibition may have been underestimated,
      at least in mammals, and that tissue pre-incubation with glutamine and pyridoxal
      5'-phosphate should yield a more precise estimate of outer retinal processing.

PMID- 21091476
TI  - Rapid de-esterification and loss of eicosapentaenoic acid from rat brain
      phospholipids: an intracerebroventricular study.
AB  - Eicosapentaenoic acid (EPA, 20:5n-3) is being explored as a therapy in
      neurological diseases and disorders. Although it is known that palmitate is the
      most abundant fatty acid in the brain while EPA is one of the lowest, the
      mechanism by which the brain maintains this balance is unclear. Therefore, to
      trace the metabolism of these fatty acids in the brain, (14) C-palmitate or (14)
      C-EPA was administered via intracerebroventricular infusion to rats. From 4 to
      128 days post-infusion, brains were collected after head-focused, high-energy
      microwave irradiation for biochemical analysis. At day 4 post-infusion, 57% (82
      +/- 26 nCi) of the total phospholipid radioactivity in (14) C-palmitate-infused
      brains was intact palmitate; whereas in (14) C-EPA-infused brains, 9% (2 +/- 0.9
      nCi) of the radioactivity was intact EPA. The half-life of esterified (14) C
      palmitate and (14) C-EPA was 32 +/- 4 (2% loss per day) and 5 +/- 0.2 days (14%
      loss per day), respectively. Radioactivity was also detected in other saturates,
      monounsaturates, and cholesterol, suggesting that the infused radiolabeled fatty
      acids were beta-oxidized. In conclusion, the low concentration of EPA in brain
      phospholipids may be the result of extensive metabolism of EPA, in part by beta
      oxidation, upon entry into the brain and upon de-esterification from
      phospholipids.

PMID- 21091477
TI  - Distribution of stomatin expressing in the central nervous system and its up
      regulation in cerebral cortex of rat by hypoxia.
AB  - Stomatin is an important membrane raft protein which can combine skeleton
      protein, some ion channel, and transporter to regulate their functions. However,
      until now no data on its expression and function in CNS are available. In this
      study, we examined distribution of stomatin in CNS of rat, and investigated the
      effects of hypoxia exposure and glucocorticoid on stomatin expression in cerebral
      cortex of rat. Immunofluorescence staining revealed a broad expression of
      stomatin protein in many areas of adult rat brain and spinal cord, including the
      ventral horn of spinal cord, causal magnocellular nucleus of hypothalamus, the V
      layer of the cerebral cortex, solitary nucleus, 10 and 12 nuclei, and so on.
      Hypoxia or ischemic hypoxia significantly up-regulated stomatin expression in
      cerebral cortex, and the up-regulation was independent on adrenocortical steroids
      since it also occurred in adrenalectomized (ADX) rats. Moreover, treatment of ADX
      or sham-operated rats with dexamethasone, a synthetic glucocorticoid alone could
      significantly stimulate expression of stomatin in lung and heart, but not in
      cerebral cortex. However, dexamethasone could enhance the hypoxia-stimulated
      expression of stomatin in cerebral cortex of ADX rats. These findings suggested
      that stomatin might be involved in various physiological functions and cellular
      events of neurons in CNS under physiological conditions and play a potential
      protective role under hypoxic conditions.

PMID- 21091478
TI  - Presenilin-1 but not amyloid precursor protein mutations present in mouse models
      of Alzheimer's disease attenuate the response of cultured cells to gamma
      secretase modulators regardless of their potency and structure.
AB  - gamma-Secretase modulators (GSMs) inhibit the generation of amyloidogenic Abeta42
      peptides and are promising agents for treatment or prevention of Alzheimer's
      disease (AD). Recently, a second generation of GSMs with favorable
      pharmacological properties has emerged, but preclinical studies to assess their
      efficacy in vivo are lacking. Such studies rely on transgenic mouse models that
      express amyloid precursor protein (APP) and presenilin (PSEN) mutations
      associated with early-onset familial AD. Previously, we have shown that certain
      PSEN1 mutations attenuated the response of cultured cells to GSMs and potentially
      confound in vivo studies in AD mouse models. However, different combinations of
      familial AD mutations might have synergistic or opposing effects, and we have now
      systematically determined the response of APP and PSEN1 mutations present in
      current AD models. Using a potent acidic GSM, we found that APP mutations, either
      single mutations or in combination, did not affect the potency of GSMs. In
      contrast, all PSEN1 mutations that have been used to accelerate pathological
      changes in AD models strongly attenuated the Abeta42-lowering activity of GSMs
      with two exceptions (M146L, A246E). Similar results were obtained with potent non
      acidic GSMs indicating that the attenuating effect of PSEN1 mutations cannot
      simply be overcome by increased potency or structural changes. Notably, two non
      acidic compounds fully compensated the attenuating effect of the PSEN1-G384A
      mutation. Taken together, our findings indicate that most AD models with rapid
      pathology and advanced phenotypes are unsuitable for preclinical GSM studies.
      However, we also provide evidence that additional compound screens could discover
      GSMs that are able to break the attenuating effects of PSEN mutations.

PMID- 21091479
TI  - Environment-dependent inbreeding depression: its ecological and evolutionary
      significance.
AB  - Inbreeding depression is a major evolutionary and ecological force that
      influences population dynamics and the evolution of inbreeding-avoidance traits
      such as mating systems and dispersal. There is now compelling evidence that
      inbreeding depression is environment-dependent. Here, we discuss ecological and
      evolutionary consequences of environment-dependent inbreeding depression. The
      environmental dependence of inbreeding depression may be caused by environment
      dependent phenotypic expression, environment-dependent dominance, and environment
      dependent natural selection. The existence of environment-dependent inbreeding
      depression challenges classical models of inbreeding as caused by unconditionally
      deleterious alleles, and suggests that balancing selection may shape inbreeding
      depression in natural populations; loci associated with inbreeding depression in
      some environments may even contribute to adaptation to others. Environment
      dependent inbreeding depression also has important, often neglected, ecological
      and evolutionary consequences: it can influence the demography of marginal or
      colonizing populations and alter adaptive optima of mating systems, dispersal,
      and their associated traits. Incorporating the environmental dependence of
      inbreeding depression into theoretical models and empirical studies is necessary
      for understanding the genetic and ecological basis of inbreeding depression and
      its consequences in natural populations.

PMID- 21091482
TI  - Nitric oxide-dependent pigment migration induced by ultraviolet radiation in
      retinal pigment cells of the crab Neohelice granulata.
AB  - The purpose of this study was to verify the occurrence of pigment dispersion in
      retinal pigment cells exposed to UVA and UVB radiation, and to investigate the
      possible participation of a nitric oxide (NO) pathway. Retinal pigment cells from
      Neohelice granulata were obtained by cellular dissociation. Cells were analyzed
      for 30 min in the dark (control) and then exposed to 1.1 and 3.3 J cm(-2) UVA,
      0.07 and 0.9 J cm(-2) UVB, 20 nmbeta-PDH (pigment dispersing hormone) or 10 MUm
      SIN-1 (NO donor). Histological analyses were performed to verify the UV effect in
      vivo. Cultured cells were exposed to 250 MUm L-NAME (NO synthase blocker) and
      afterwards were treated with UVA, UVB or beta-PDH. The retinal cells in culture
      displayed significant pigment dispersion in response to UVA, UVB and beta-PDH.
      The same responses to UVA and UVB were observed in vivo. SIN-1 did not induce
      pigment dispersion in the cell cultures. L-NAME significantly decreased the
      pigment dispersion induced by UVA and UVB but not by beta-PDH. All retinal cells
      showed an immunopositive reaction against neuronal nitric oxide synthases.
      Therefore, UVA and UVB radiation are capable of inducing pigment dispersion in
      retinal pigment cells of Neohelice granulata and this dispersion may be nitric
      oxide synthase dependent.

PMID- 21091483
TI  - Spectral discrimination of benign and malignant prostate tissues--a preliminary
      report.
AB  - In this preliminary report, benign (n=8) and malignant (n=5) prostate tissues, in
      vitro, have been taken through autofluorescence spectroscopy. Employing Stokes'
      shift spectra and fluorescence emission spectra as tools of analysis, we were
      able to discriminate the two sets of tissues with sensitivity and specificity in
      excess of 85%. When the excised prostate chips were scanned with a spatial
      resolution of 1 mm, the epicenter of malignancy also could be delineated.

PMID- 21091484
TI  - Assessment of the photoprotection properties of sunscreens by chromatographic
      measurement of DNA damage in skin explants.
AB  - Evaluation of the photoprotection provided by sunscreens is performed either
      through the induction of erythema and expressed as the sun protection factor
      (SPF), or by the UVA-mediated persistent pigment darkening (PPD). None of these
      two endpoints has a link with skin cancer, the most deleterious consequence of
      excess exposure to solar UV radiation. We thus set up a complementary approach to
      evaluate the protection provided by sunscreens to the genome of human skin. This
      is based on the quantification of the thymine cyclobutane dimer (TT-CPD), the
      main DNA lesion induced by both UVB and UVA radiations. Irradiations were
      performed ex vivo on human skin explants and the level of TT-CPD in DNA was
      determined by HPLC associated with tandem mass spectrometry. The technique was
      first optimized and validated with three standard sunscreens. The study was then
      extended to the evaluation of a commercial high SPF sunscreen exhibiting
      efficient UVA photoprotection. The DNA protecting factor was found to reflect the
      ratio between UVB and UVA photoprotection, although the absolute values of the
      genomic protection were, as a general trend, lower than either SPF or PPD. These
      data show the usefulness of the proposed approach for the evaluation of the
      genoprotection afforded by sunscreens.

PMID- 21091485
TI  - UVR emissions from solaria in Australia and implications for the regulation
      process.
AB  - To assist in the development of the 2008 Australian/New Zealand standard on
      solaria and related regulations, Australian Radiation Protection and Nuclear
      Safety Agency scientists visited a number of tanning establishments during 2008
      to measure the intensity and spectral distribution of the ultraviolet radiation
      (UVR) emissions from a range of solaria. The 2002 Australian/New Zealand Standard
      "Solaria for cosmetic purposes" (AS/NZS 2635) allowed a maximum UVR output from
      solaria of UV Index 60, a compromise between the solarium industry who wanted no
      upper limit and the health agencies who wanted to limit intensity. Of the 20
      solaria examined in detail, only one had emissions of intensity less than UV
      Index 12, typical of mid-latitude summer sunlight, 15 units emitted more than UV
      Index 20, while three units emitted at intensities above UV Index 36, the maximum
      allowed by the new standard, AS/NZS 2635 (2008) and would thus not comply. UVA
      emissions ranged from 98W.m(-2) up to a maximum of 438W.m(-2) , more than six
      times the UVA content of mid-latitude summer sunshine. The results indicate that
      solaria users in Australia have access to solaria that are high intensity units
      with both significantly higher UVB and UVA emissions than sunlight, with
      implications for resultant adverse health effects.

PMID- 21091486
TI  - Absorption and emission spectroscopic characterization of lumichrome in aqueous
      solutions.
AB  - The spectroscopic behavior of lumichrome (7,8-dimethyl-alloxazine, LC) in aqueous
      solutions in a pH range from -1.08 to 14.6 is studied. Absorption spectra,
      fluorescence quantum distributions, quantum yields, and lifetimes are determined.
      The ionization stage of ground-state LC changes with rising pH from the cationic
      form (LCH(2)(+)) to the neutral form (LCH) with a mid-point pH of pK(c) ~ -0.53,
      and to the anionic form (LC(-)) with a mid-point pH of pK(a) ~ 12.5. Above pH 7 a
      partial ground-state tautomerization of LCH to 7,8-dimethyl-isoalloxazine (IAH)
      occurs by N1-N10 intra-molecular proton transfer. For pH > pK(a) ~ 12.5 LCH and
      IAH change to the anionic forms LC(-) and IA(-), and above pH 14 LC(-)
      tautomerizes completely to IA(-). In the excited state some neutral lumichrome
      (LCH*) converts to cationic lumichrome (LCH(2)(+)) at low pH by proton transfer
      from H(3)O(+) to LCH*. No photoinduced excited-state tautomerization of
      lumichrome was observed. LCH for pH > 3 and IAH are reasonably fluorescent. The
      fluorescence efficiencies of LC(-) and IA(-) are lower than those of LCH and IAH.
      The fluorescence of LCH(2)(+) is strongly quenched likely by intra-molecular
      diabatic charge transfer and excited-state relaxation by potential surface
      touching with the ground state.

PMID- 21091487
TI  - Transmission of light to the young primate retina: possible implications for the
      formation of lipofuscin.
AB  - The purpose of this study was to determine the transmission properties of the
      anterior segment of young primate eyes and potentially relate those changes to
      photochemical processes in the retina that lead to the early, rapid formation of
      lipofuscin. A simple method has been developed to determine the optical
      properties of the anterior segment of the intact eye. Using this technique, the
      transmission/absorption properties of primate cadaver eyes were determined. A
      young primate anterior segment has a maximum absorption at 365nm due to the
      presence of the O-beta-glucoside of 3-hydroxykynurenine in the lens. This is
      synthesized in the last trimester of gestation. Although this compound filters
      out most of the UV light from reaching the retina, there is a small window of
      transmission centered on an absorption minimum at 320nm. This closes by the
      second decade of life. The window of transmission of UV light to the primate
      retina may explain the initial accelerated formation of lipofuscin in the young
      human retina by a photochemical process. This would be exacerbated by any
      decrease in the ozone layer with concomitant increase in UV-B reaching the
      earth's surface.

PMID- 21091488
TI  - Radical protection by sunscreens in the infrared spectral range.
AB  - One essential reason for skin ageing is the formation of free radicals by
      excessive or unprotected sun exposure. Recently, free radical generation in skin
      has been shown to appear not only after irradiation in the UV wavelength range
      but also in the infrared (IR) spectral range. Sunscreens are known to protect
      against radicals generated by UV radiation; however, no data exist for those
      generated by IR radiation. This paper has investigated four different,
      commercially available sunscreens and one COLIPA standard with regard to radical
      formation in the skin after IR irradiation, using electron paramagnetic resonance
      spectroscopy. The use of sunscreens has led to reduced amounts of radicals
      compared to untreated skin. Furthermore, absorption and scattering properties and
      the radical protection factor of the formulations were determined to investigate
      their influence on the radical protection of the skin. None of these formulations
      contained an optical absorber in the IR range. The protection efficiency of the
      sunscreens was shown as being induced by the high scattering properties of the
      sunscreens, as well as the antioxidants contained in the formulations.

PMID- 21091489
TI  - Deactivation of excited states of kynurenine covalently linked to nitroxides.
AB  - Due to ability of stable nitroxides to interact with free radicals, they are used
      as antioxidants for therapeutic and research goals in biology and medicine. A
      modern trend in medical chemistry is the design of multifunctional molecules such
      as UV absorbers covalently bound to nitroxides, which provides both UV protection
      and antioxidant properties combined in the same molecule. In the present work, we
      report the synthesis of conjugates of a natural UV filter kynurenine (KN) with
      nitroxides (KN-RNO(*) conjugates) and the study of their photochemical properties
      in aqueous and methanol solutions. Due to the spin-exchange interaction between
      KN and nitroxide moieties, the triplet lifetimes in conjugates are much shorter
      than in KN molecule, but the triplet quantum yields are significantly higher. The
      reaction of intramolecular electron transfer between photoexcited KN and
      nitroxide moieties is the main factor determining the quantum yield of KN-RNO(*)
      conjugates photodecomposition. Consequently, KN-RNO(*) conjugates in aqueous
      solution are photochemically less stable than the parent KN molecule.
      Nevertheless, the photostability of KN-RNO(*) conjugates is much higher than that
      of cinnamates which are widely used as UV absorbers in modern sunscreen
      formulations. Thus, the combination of the endogenous chromophore KN with
      nitroxides is very promising for medical applications.

PMID- 21091490
TI  - The measurement and analysis of normal incidence solar UVB radiation and its
      application to the photoclimatherapy protocol for psoriasis at the Dead Sea,
      Israel.
AB  - The broad-band normal incidence UVB beam radiation has been measured at Neve
      Zohar, Dead Sea basin, using a prototype tracking instrument composed of a Model
      501A UV-Biometer mounted on an Eppley Solar Tracker Model St-1. The diffuse and
      beam fraction of the solar global UVB radiation have been determined using the
      concurrently measured solar global UVB radiation. The diffuse fraction was
      observed to exceed 80% throughout the year. The application of the results of
      these measurements to the possible revision of the photoclimatherapy protocol for
      psoriasis patients at the Dead Sea medical spas is now under investigation. The
      suggested revision would enable the sun-exposure treatment protocol to take
      advantage of the very high diffuse fraction by allowing the patient to receive
      the daily dose of UVB radiation without direct exposure to the sun, viz. receive
      the diffuse UVB radiation under a sunshade. This would require an increase in sun
      exposure time intervals, as the UVB radiation intensity beneath a sunshade is
      less than that on an exposed surface.

PMID- 21091491
TI  - Does using stepwise variable selection to build sequential path analysis models
      make sense?
AB  - Causal inference methods--mainly path analysis and structural equation modeling-
      offer plant physiologists information about cause-and-effect relationships among
      plant traits. Recently, an unusual approach to causal inference through stepwise
      variable selection has been proposed and used in various works on plant
      physiology. The approach should not be considered correct from a biological point
      of view. Here, it is explained why stepwise variable selection should not be used
      for causal inference, and shown what strange conclusions can be drawn based upon
      the former analysis when one aims to interpret cause-and-effect relationships
      among plant traits.

PMID- 21091492
TI  - Initial resuscitation with plasma and other blood components reduced bleeding
      compared to hetastarch in anesthetized swine with uncontrolled splenic
      hemorrhage.
AB  - BACKGROUND: Damage control resuscitation recommends use of more plasma and less
      crystalloid as initial resuscitation in treating hemorrhage. The purpose of this
      study was to evaluate resuscitation with either blood components or conventional
      fluids on coagulation and blood loss. STUDY DESIGN AND METHODS: Isofluorane
      anesthetized, instrumented pigs (eight per group) underwent controlled hemorrhage
      of 24 mL/kg, 20-minute shock period, splenic injury with 15-minute initial
      bleeding, and hypotensive fluid resuscitation. Lactated Ringer's (LR) was infused
      at 45 mL/kg while hetastarch (high-molecular-weight hydroxyethyl starch 6%,
      Hextend, Hospira, Inc., Lake Forest, IL) and blood component (fresh-frozen plasma
      [FFP], 1:1 FFP:[red blood cells] RBCs, 1:4 FFP : RBCs, and fresh whole blood
      [FWB]) were infused at 15 mL/kg. Postresuscitation blood loss (PRBL),
      hemodynamics, coagulation, hematocrit, and oxygen metabolism were measured
      postinjury for 5 hours. RESULTS: Resuscitation with any blood component reduced
      PRBL of 52% to 70% compared to Hextend, with FFP resulting in the lowest PRBL.
      PRBL with LR (11.5 +/- 3.0 mL/kg) was not significantly different from Hextend
      (17.9 +/- 2.5 mL/kg) or blood components (range, 5.5 +/- 1.5 to 8.6 +/- 2.6
      mL/kg). The volume expansion effect of LR was transient. All fluids produced
      similar changes in hemodynamics, oxygen delivery, and demand despite the oxygen
      carrying capacity of RBC-containing fluids. Compared with other fluids, Hextend
      produced greater hemodilution and reduced coagulation measures, which could be
      caused by an indirect dilutional effect or a direct hypocoagulable effect.
      CONCLUSIONS: These data suggest that blood products as initial resuscitation
      fluids reduced PRBL from a noncompressible injury compared to Hextend, preserved
      coagulation, and provided sustained volume expansion. There were no differences
      on PRBL among RBCs-to-FFP, FWB, or FFP in this nonmassive transfusion model.

PMID- 21091493
TI  - Comparative study of subcutaneous tissue responses to a novel root-end filling
      material and white and grey mineral trioxide aggregate.
AB  - AIM: To compare the subcutaneous tissue response to grey mineral trioxide
      aggregate (GMTA), white mineral trioxide aggregate (WMTA) and a new experimental
      cement (calcium enriched cement, CEM). METHODOLOGY: Thirty-six Wistar male albino
      rats each received three implants, containing one of the tested materials, and an
      empty tube as a control. Seven, 30 and 60 days after implantation, the animals
      were sacrificed. After histological preparation and H&E staining, the specimens
      were evaluated for capsule thickness, necrosis, and for the type, the severity,
      and the extent of inflammation. Kruskal Wallis and Chi-square tests were used for
      data analysis. RESULTS: After 1 week, CEM produced no necrosis compared to both
      types of WMTA and GMTA (P = 0.007). After 30 days, GMTA specimens had
      significantly less inflammation compared with WMTA and CEM (P = 0.011). After 60
      days, less inflammation was associated with CEM specimens (P = 0.0001) compared
      to the other materials. Dystrophic calcifications in the connective tissue
      adjacent to all experimental material were detected. CONCLUSION: Histological
      observation illustrated that all materials were well tolerated by the
      subcutaneous tissues.

PMID- 21091494
TI  - Evaluation of physicochemical properties of four root canal sealers.
AB  - AIM: To assess the physicochemical properties and the surface morphology of AH
      Plus, GuttaFlow, RoekoSeal and Activ GP root canal sealers. METHODOLOGY: Five
      samples of each material were evaluated for setting time, dimensional alteration,
      solubility and radiopacity tests, according to ANSI/ADA Specification 57. A total
      of 50 mL of deionized distilled water from the solubility tests were used to
      measure the metal solubility by atomic absorption spectrometry. The morphologies
      of the external surface and the cross-section of the samples were analysed by
      means of a scanning electron microscope (SEM). Statistical analysis was performed
      by using one-way anova and post hoc Tukey-Kramer tests with the null hypothesis
      set as 5%. RESULTS: AH Plus had the longest setting time (580.6 +/- 3.05 min)
      (P<0.05). Activ GP did not have a mean value on the radiopacity and solubility
      tests (1.31 +/- 0.35 mm and 11.8 +/- 0.43%, respectively) in accordance with
      ANSI/ADA, being significantly different from the other materials (P<0.05), which
      had mean values for these tests in accordance with the ADA's requirements.
      GuttaFlow was the only sealer that conformed to the Specification 57 concerning
      the dimensional alteration test (0.44 +/- 0.16%) (P<0.05). The spectrometry test
      revealed significant Ca(2+), K(+), Zn(2+) ion release from Activ GP sealer (32.57
      +/- 5.0, 1.57 +/- 0.22 and 8.20 +/- 1.74 MUg mL(-1), respectively). In SEM
      analysis, the loss of matrix was evident and the filler particles were more
      distinguishable in all groups. CONCLUSIONS: The setting time of all sealers was
      in accordance with ANSI/ADA's requirements. Activ GP did not fulfill ANSI/ADA's
      protocols regarding radiopacity, dimensional alteration and solubility. GuttaFlow
      was the only sealer that conformed to the Specification 57 in all tests. SEM
      analysis revealed that the surfaces of all sealers had micromorphological changes
      after the solubility test.

PMID- 21091495
TI  - Use of CBCT to identify the morphology of maxillary permanent molar teeth in a
      Chinese subpopulation.
AB  - AIM: To investigate variations in root canal configuration in the maxillary
      permanent molar teeth of a Chinese subpopulation using cone-beam computed
      tomography (CBCT). METHODOLOGY: A total of 269 patients with healthy, untreated,
      well-developed maxillary molars were enrolled, including those suffering facial
      trauma, and those who required a pre-operative assessment for implants.
      Radiographic examination by CBCT was conducted as part of their routine
      examination, diagnosis and treatment planning. Overall, 299 maxillary first and
      210 maxillary second molar teeth were examined in vivo by CBCT. The number of
      roots, the number of canals per root, the canal configuration and the presence of
      additional mesiobuccal canals were recorded. Vertucci's classification for root
      canal configurations was utilized. RESULTS: All maxillary first molars had three
      separate roots; however, 52% of mesiobuccal (MB) roots had two canals with the
      remainder having one. All distobuccal and palatal roots had Vertucci Type I canal
      configurations. When the MB2 canal was present, 14, 69 and 16% of MB roots had
      Type II, IV and V canal configurations, respectively. The root canal system of
      the maxillary first molar teeth could be categorized into two variants: one with
      three separate roots with one canal in each of the distobuccal and palatal roots
      and two canals in the MB root, and the other with three separate roots with one
      canal in each root. Of 210 maxillary second molars, 10% had one root, 8% two
      roots and 81% three roots. Of the MB roots, 22% had two canals with the remainder
      having one. When the MB2 canal was present, 18%, 58%, 10% and 3% of MB roots had
      type II, IV, V and VI canal configurations, respectively. The root canal system
      of the maxillary second molar could be categorized into eight variants.
      CONCLUSIONS: Mesiobucccal roots of maxillary molar teeth had more variation in
      their canal system than the distobuccal or palatal roots. The root canal
      configuration of the maxillary second molars was more variable than that of the
      first molars. CBCT can enhance detection and mapping of the mesiobuccal root
      canal system with the potential to improve the quality of root canal treatment.

PMID- 21091496
TI  - Conserved components, but distinct mechanisms for the placement and assembly of
      the cell division machinery in unicellular and filamentous ascomycetes.
AB  - Cytokinesis is essential for cell proliferation, yet its molecular description is
      challenging, because >100 conserved proteins must be spatially and temporally co
      ordinated. Despite the high importance of a tight co-ordination of cytokinesis
      with chromosome and organelle segregation, the mechanism for determining the cell
      division plane is one of the least conserved aspects of cytokinesis in eukaryotic
      cells. Budding and fission yeast have developed fundamentally distinct mechanisms
      to ensure proper nuclear segregation. The extent to which these pathways are
      conserved in multicellular fungi remains unknown. Recent progress indicates
      common components, but different mechanisms that are required for proper
      selection of the septation site in the different groups of Ascomycota. Cortical
      cues are used in yeast- and filament-forming species of the Saccharomycotina
      clade that are established at the incipient bud site or the hyphal tip
      respectively. In contrast, septum formation in the filament-forming
      Pezizomycotina species Aspergillus nidulans and Neurospora crassa seems more
      closely related to the fission yeast programme in that they may combine mitotic
      signals with a cell end-based marker system and Rho GTPase signalling. Thus,
      significant differences in the use and connection of conserved signalling modules
      become apparent that reflect the phylogenetic relationship of the analysed
      models.

PMID- 21091497
TI  - The dawning of a 'Golden era' in lantibiotic bioengineering.
AB  - There are many examples of highly modified antimicrobial peptides in nature, many
      of which are non-ribosomally synthesized. However, the bacterial lantibiotics are
      produced as gene-encoded pre-peptides that are subsequently modified by dedicated
      enzyme systems to form extraordinarily potent inhibitors. Consequently, they are
      much more amenable to bioengineering which could lead to the generation of a new
      arsenal of potent antimicrobials. However, although bioengineering of these
      compounds has been underway for at least two decades, significant progress has
      only been reported in recent years. This review charts these recent developments
      which suggest that we are entering a 'Golden era' of lantibiotic bioengineering.

PMID- 21091498
TI  - Multiple regions along the Escherichia coli FtsK protein are implicated in cell
      division.
AB  - Escherichia coli FtsK is a large 1329 aa integral membrane protein, which links
      cell division and chromosome segregation through the respective activities of its
      200 aa amino-terminal domain, FtsK(N), and its 500 aa carboxy-terminal domain,
      FtsK(C). A long 600 aa linker, FtsK(L), connects these two domains. Only FtsK(N)
      is essential for cell division. However, previous observations suggested that the
      cytoplasmic part of FtsK also participates in the process of septation. Here, we
      identify two distinct regions within FtsK(L), FtsK(179-331) and FtsK(332-641),
      which together with FtsK(N), are required for normal septation. We discuss how
      the implication of multiple regions along the FtsK protein in cell division could
      participate in the co-ordination of this process with the last stages of
      chromosome segregation.

PMID- 21091499
TI  - Charged residues in the cytoplasmic loop of MotA are required for stator assembly
      into the bacterial flagellar motor.
AB  - MotA and MotB form a transmembrane proton channel that acts as the stator of the
      bacterial flagellar motor to couple proton flow with torque generation. The C
      terminal periplasmic domain of MotB plays a role in anchoring the stators to the
      motor. However, it remains unclear where their initial binding sites are. Here,
      we constructed Salmonella strains expressing GFP-MotB and MotA-mCherry and
      investigated their subcellular localization by fluorescence microscopy. Neither
      the D33N and D33A mutations in MotB, which abolish the proton flow, nor depletion
      of proton motive force affected the assembly of GFP-MotB into the motor,
      indicating that the proton translocation activity is not required for stator
      assembly. Overexpression of MotA markedly inhibited wild-type motility, and it
      was due to the reduction in the number of functional stators. Consistently, MotA
      mCherry was observed to colocalize with GFP-FliG even in the absence of MotB.
      These results suggest that MotA alone can be installed into the motor. The R90E
      and E98K mutations in the cytoplasmic loop of MotA (MotA(C) ), which has been
      shown to abolish the interaction with FliG, significantly affected stator
      assembly, suggesting that the electrostatic interaction of MotA(C) with FliG is
      required for the efficient assembly of the stators around the rotor.

PMID- 21091500
TI  - Helicobacter pylori HP0518 affects flagellin glycosylation to alter bacterial
      motility.
AB  - Helicobacter pylori is a human gastric pathogen associated with gastric and
      duodenal ulcers as well as gastric cancer. Mounting evidence suggests this
      pathogen's motility is prerequisite for successful colonization of human gastric
      tissues. Here, we isolated an H. pylori G27 HP0518 mutant exhibiting altered
      motility in comparison to its parental strain. We show that the mutant's
      modulated motility is linked to increased levels of O-linked glycosylation on
      flagellin A (FlaA) protein. Recombinant HP0518 protein decreased glycosylation
      levels of H. pylori flagellin in vitro, indicating that HP0518 functions in
      deglycosylation of FlaA protein. Furthermore, mass spectrometric analysis
      revealed increased glycosylation of HP0518 FlaA was due to a change in
      pseudaminic acid (Pse) levels on FlaA; HP0518 mutant-derived flagellin contained
      approximately threefold more Pse than the parental strain. Further phenotypic and
      molecular characterization demonstrated that the hyper-motile HP0518 mutant
      exhibits superior colonization capabilities and subsequently triggers enhanced
      CagA phosphorylation and NF-kappaB activation in AGS cells. Our study shows that
      HP0518 is involved in the deglycosylation of flagellin, thereby regulating
      pathogen motility. These findings corroborate the prominent function of H. pylori
      flagella in pathogen-host cell interactions and modulation of host cell
      responses, likely influencing the pathogenesis process.

PMID- 21091501
TI  - Bacillus subtilis MreB paralogues have different filament architectures and lead
      to shape remodelling of a heterologous cell system.
AB  - Like many bacteria, Bacillus subtilis cells contain three actin-like MreB
      proteins. We show that the three paralogues, MreB, Mbl and MreBH, have different
      filament architectures in a heterologous cell system, and form straight
      filaments, helices or ring structures, different from the regular helical
      arrangement in B. subtilis cells. However, when coexpressed, they colocalize into
      a single filamentous helical structure, showing that the paralogues influence
      each other's filament architecture. Ring-like MreBH structures can be converted
      into MreB-like helical filaments by a single point mutation affecting subunit
      contacts, showing that MreB paralogues feature flexible filament arrangements.
      Time-lapse and FRAP experiments show that filaments can extend as well as shrink
      at both ends, and also show internal rearrangement, suggesting that filaments
      consist of overlapping bundles of shorter filaments that continuously turn over.
      Upon induction in Escherichia coli cells, B. subtilis MreB (BsMreB) filaments
      push the cells into strikingly altered cell morphology, showing that MreB
      filaments can change cell shape. E. coli cells with a weakened cell wall were
      ruptured upon induction of BsMreB filaments, suggesting that the bacterial actin
      orthologue may exert force against the cell membrane and envelope, and thus
      possibly plays an additional mechanical role in bacteria.

PMID- 21091502
TI  - Non-stop mRNA decay initiates at the ribosome.
AB  - The translation machinery deciphers genetic information encoded within mRNAs to
      synthesize proteins needed for various cellular functions. Defective mRNAs that
      lack in-frame stop codons trigger non-productive stalling of ribosomes. We
      investigated how cells deal with such defective mRNAs, and present evidence to
      demonstrate that RNase R, a processive 3'-to-5' exoribonuclease, is recruited to
      stalled ribosomes for the specific task of degrading defective mRNAs. The
      recruitment process is selective for non-stop mRNAs and is dependent on the
      activities of SmpB protein and tmRNA. Most intriguingly, our analysis reveals
      that a unique structural feature of RNase R, the C-terminal lysine-rich (K-rich)
      domain, is required both for productive ribosome engagement and targeted non-stop
      mRNA decay activities of the enzyme. These findings provide new insights into how
      a general RNase is recruited to the translation machinery and highlight a novel
      role for the ribosome as a platform for initiating non-stop mRNA decay.

PMID- 21091504
TI  - Partitioning of P1 plasmids by gradual distribution of the ATPase ParA.
AB  - Recently, it has been reported that prokaryotes also have a mitotic-like
      apparatus in which polymerized fibres govern the bipolar movement of chromosomes
      and plasmids. Here, we show evidence that a non-mitotic-like apparatus that does
      not form polymerized filaments carries out plasmid partitioning. P1 ParA, which
      is a DNA-binding ATPase protein, was found to be distributed through the whole
      nucleoid and formed a dense spot at the centre of the nucleoid. The fluorescent
      intensity of the ParA spot blinked, and then the spot gradually migrated from the
      midcell to a cell quarter position. Such distribution was not observed in
      anucleate cells, suggesting that the nucleoid could be a matrix for gradual
      distribution of ParA. Plasmid DNA constantly colocalized at the spot of ParA and
      migrated according to spot migration and separation. Thus, the gradient
      distribution of ParA determines the destination of partitioning plasmids and may
      direct plasmids to the cell quarters.

PMID- 21091503
TI  - The Vibrio cholerae virulence regulatory cascade controls glucose uptake through
      activation of TarA, a small regulatory RNA.
AB  - Vibrio cholerae causes the severe diarrhoeal disease cholera. A cascade of
      regulators controls expression of virulence determinants in V. cholerae at both
      transcriptional and post-transcriptional levels. ToxT is the direct transcription
      activator of the major virulence genes in V. cholerae. Here we describe TarA, a
      highly conserved, small regulatory RNA, whose transcription is activated by ToxT
      from toxboxes present upstream of the ToxT-activated gene tcpI. TarA regulates
      ptsG, encoding a major glucose transporter in V. cholerae. Cells overexpressing
      TarA exhibit decreased steady-state levels of ptsG mRNA and grow poorly in
      glucose-minimal media. A mutant lacking the ubiquitous regulatory protein Hfq
      expresses diminished TarA levels, indicating that TarA likely interacts with Hfq
      to regulate gene expression. RNAhybrid analysis of TarA and the putative ptsG
      mRNA leader suggests potential productive base-pairing between these two RNA
      molecules. A V. cholerae mutant lacking TarA is compromised for infant mouse
      colonization in competition with wild type, suggesting a role in the in vivo
      fitness of V. cholerae. Although somewhat functionally analogous to SgrS of
      Escherichia coli, TarA does not encode a regulatory peptide, and its expression
      is activated by the virulence gene pathway in V. cholerae and not by glycolytic
      intermediates.

PMID- 21091506
TI  - Regulation of the 18 kDa heat shock protein in Mycobacterium ulcerans: an alpha
      crystallin orthologue that promotes biofilm formation.
AB  - Mycobacterium ulcerans is the causative agent of the debilitating skin disease
      Buruli ulcer, which is most prevalent in Western and Central Africa. M. ulcerans
      shares >98% DNA sequence identity with Mycobacterium marinum, however, M. marinum
      produces granulomatous, but not ulcerative, lesions in humans and animals. Here
      we report the differential expression of a small heat shock protein (Hsp18)
      between strains of M. ulcerans (Hsp18(+) ) and M. marinum (Hsp18(-) ) and
      describe the molecular basis for this difference. We show by gene deletion and
      GFP reporter assays in M. marinum that a divergently transcribed gene called
      hspR_2, immediately upstream of hsp18, encodes a MerR-like regulatory protein
      that represses hsp18 transcription while promoting its own expression. Naturally
      occurring mutations within a 70 bp segment of the 144 bp hspR_2-hsp18 intergenic
      region among M. ulcerans strains inhibit hspR_2 transcription and explain the
      Hsp18(+) phenotype. We also propose a biological role for Hsp18, as we show that
      this protein significantly enhances bacterial attachment or aggregation during
      biofilm formation. This study has uncovered a new member of the MerR family of
      transcriptional regulators and suggests that upregulation of hsp18 expression was
      an important pathoadaptive response in the evolution of M. ulcerans from a M.
      marinum-like ancestor.

PMID- 21091505
TI  - Carbon flux rerouting during Mycobacterium tuberculosis growth arrest.
AB  - A hallmark of the Mycobacterium tuberculosis life cycle is the pathogen's ability
      to switch between replicative and non-replicative states in response to host
      immunity. Transcriptional profiling by qPCR of ~ 50 M. tuberculosis genes
      involved in central and lipid metabolism revealed a re-routing of carbon flow
      associated with bacterial growth arrest during mouse lung infection. Carbon
      rerouting was marked by a switch from metabolic pathways generating energy and
      biosynthetic precursors in growing bacilli to pathways for storage compound
      synthesis during growth arrest. Results of flux balance analysis using an in
      silico metabolic network were consistent with the transcript abundance data
      obtained in vivo. Similar transcriptional changes were seen in vitro when M.
      tuberculosis cultures were treated with bacteriostatic stressors under different
      nutritional conditions. Thus, altered expression of key metabolic genes reflects
      growth rate changes rather than changes in substrate availability. A model
      describing carbon flux rerouting was formulated that (i) provides a coherent
      interpretation of the adaptation of M. tuberculosis metabolism to immunity
      induced stress and (ii) identifies features common to mycobacterial dormancy and
      stress responses of other organisms.

PMID- 21091508
TI  - Distinct functional roles of homologous Cu+ efflux ATPases in Pseudomonas
      aeruginosa.
AB  - In bacteria, most Cu(+) -ATPases confer tolerance to Cu by driving cytoplasmic
      metal efflux. However, many bacterial genomes contain several genes coding for
      these enzymes suggesting alternative roles. Pseudomonas aeruginosa has two
      structurally similar Cu(+) -ATPases, CopA1 and CopA2. Both proteins are essential
      for virulence. Expressed in response to high Cu, CopA1 maintains the cellular Cu
      quota and provides tolerance to this metal. CopA2 belongs to a subgroup of
      ATPases that are expressed in association with cytochrome oxidase subunits.
      Mutation of copA2 has no effect on Cu toxicity nor intracellular Cu levels; but
      it leads to higher H(2) O(2) sensitivity and reduced cytochrome oxidase activity.
      Mutation of both genes does not exacerbate the phenotypes produced by single-gene
      mutations. CopA1 does not complement the copA2 mutant strain and vice versa, even
      when promoter regions are exchanged. CopA1 but not CopA2 complements an
      Escherichia coli strain lacking the endogenous CopA. Nevertheless, transport
      assays show that both enzymes catalyse cytoplasmic Cu(+) efflux into the
      periplasm, albeit CopA2 at a significantly lower rate. We hypothesize that their
      distinct cellular functions could be based on the intrinsic differences in
      transport kinetic or the likely requirement of periplasmic partner Cu-chaperone
      proteins specific for each Cu(+) -ATPase.

PMID- 21091509
TI  - Involvement of the Aspergillus nidulans protein kinase C with farnesol tolerance
      is related to the unfolded protein response.
AB  - Previously, we demonstrated that the Aspergillus nidulans calC2 mutation in
      protein kinase C pkcA was able to confer tolerance to farnesol (FOH), an
      isoprenoid that has been shown to inhibit proliferation and induce apoptosis.
      Here, we investigate in more detail the role played by A. nidulans pkcA in FOH
      tolerance. We demonstrate that pkcA overexpression during FOH exposure causes
      increased cell death. FOH is also able to activate several markers of endoplasmic
      reticulum (ER) stress and the unfolded protein response (UPR). Our results
      suggest an intense cross-talk between PkcA and the UPR during FOH-induced cell
      death. Furthermore, the overexpression of pkcA increases both mRNA accumulation
      and metacaspases activity, and there is a genetic interaction between PkcA and
      the caspase-like protein CasA. Mutant analyses imply that MAP kinases are
      involved in the signal transduction in response to the effects caused by FOH.

PMID- 21091507
TI  - Enteropathogenic E. coli non-LEE encoded effectors NleH1 and NleH2 attenuate NF
      kappaB activation.
AB  - Enteric bacterial pathogens have evolved sophisticated strategies to evade host
      immune defences. Some pathogens deliver anti-inflammatory effector molecules into
      the host cell cytoplasm via a type III secretion system (T3SS). Enteropathogenic
      Escherichia coli (EPEC) inhibits inflammation by an undefined, T3SS-dependent
      mechanism. Two proteins encoded outside of the EPEC locus of enterocyte
      effacement (LEE) pathogenicity island, non-LEE-encoded effector H1 (NleH1) and H2
      (NleH2), display sequence similarity to Shigella flexneri OspG, which inhibits
      activation of the pro-inflammatory transcription factor NF-kappaB. We
      hypothesized that the anti-inflammatory effects of EPEC were mediated by NleH1
      and NleH2. In this study, we examined the effect of NleH1/H2 on the NF-kappaB
      pathway. We show that NleH1/H2 are secreted via the T3SS and that transfection of
      cells with plasmids harbouring nleH1 or nleH2 decreased IKK-beta-induced NF
      kappaB activity and attenuated TNF-alpha-induced degradation of phospho
      IkappaBalpha by preventing ubiquitination. Serum KC levels were higher in mice
      infected with DeltanleH1H2 than those infected with WT EPEC, indicating that
      NleH1/H2 dampen pro-inflammatory cytokine expression. DeltanleH1H2 was cleared
      more rapidly than WT EPEC while complementation of DeltanleH1H2 with either NleH1
      or NleH2 prolonged colonization. Together, these data show that NleH1 and NleH2
      function to dampen host inflammation and facilitate EPEC colonization during
      pathogenesis.

PMID- 21091510
TI  - Nitric oxide-sensitive and -insensitive interaction of Bacillus subtilis NsrR
      with a ResDE-controlled promoter.
AB  - NsrR is a nitric oxide (NO)-sensitive transcription repressor that controls NO
      metabolism in a wide range of bacteria. In Bacillus subtilis, NsrR represses
      transcription of the nitrite reductase (nasDEF) genes that are under positive
      control of the ResD-ResE two-component signal transduction system. Derepression
      is achieved by reaction of NO with NsrR. Unlike some NsrR orthologues that were
      shown to contain a NO-sensitive [2Fe-2S] cluster, B. subtilis NsrR, when purified
      anaerobically either from aerobic or from anaerobic Escherichia coli and B.
      subtilis cultures, contains a [4Fe-4S] cluster. [4Fe-4S]-NsrR binds around the 
      35 element of the nasD promoter with much higher affinity than apo-NsrR and
      binding of [4Fe-4S]-NsrR, but not apo-protein, is sensitive to NO. RNA polymerase
      and phosphorylated ResD make a ternary complex at the nasD promoter and NsrR
      dissociates the preformed ternary complex. In addition to the -35 region, NsrR
      binds to two distinct sites of the upstream regulatory region where ResD also
      binds. These interactions, unlike the high-affinity site binding, do not depend
      on the NsrR [4Fe-4S] cluster and binding is not sensitive to NO, suggesting a
      role for apo-NsrR in transcriptional regulation.

PMID- 21091511
TI  - Distinct glycan-charged phosphodolichol carriers are required for the assembly of
      the pentasaccharide N-linked to the Haloferax volcanii S-layer glycoprotein.
AB  - In Archaea, dolichol phosphates have been implicated as glycan carriers in the N
      glycosylation pathway, much like their eukaryal counterparts. To clarify this
      relation, highly sensitive liquid chromatography/mass spectrometry was employed
      to detect and characterize glycan-charged phosphodolichols in the haloarchaeon
      Haloferax volcanii. It is reported that Hfx. volcanii contains a series of C(55)
      and C(60) dolichol phosphates presenting saturated isoprene subunits at the alpha
      and omega positions and sequentially modified with the first, second, third and
      methylated fourth sugar subunits comprising the first four subunits of the
      pentasaccharide N-linked to the S-layer glycoprotein, a reporter of N
      glycosylation. Moreover, when this glycan-charged phosphodolichol pool was
      examined in cells deleted of agl genes encoding glycosyltransferases
      participating in N-glycosylation and previously assigned roles in adding
      pentasaccharide residues one to four, the composition of the lipid-linked glycans
      was perturbed in the identical manner as was S-layer glycoprotein N-glycosylation
      in these mutants. In contrast, the fifth sugar of the pentasaccharide, identified
      as mannose in this study, is added to a distinct dolichol phosphate carrier. This
      represents the first evidence that in Archaea, as in Eukarya, the
      oligosaccharides N-linked to glycoproteins are sequentially assembled from
      glycans originating from distinct phosphodolichol carriers.

PMID- 21091512
TI  - Calcium ion-mediated assembly and function of glycosylated flagellar sheath of
      marine magnetotactic bacterium.
AB  - Flagella of some pathogens or marine microbes are sheathed by an apparent
      extension of the outer cell membrane. Although flagellar sheath has been reported
      for almost 60 years, little is known about its function and the mechanism of its
      assembly. Recently, we have observed a novel type of sheath that encloses a
      flagellar bundle, instead of a single flagellum, in a marine magnetotactic
      bacterium MO-1. Here, we reported isolation and characterization of the sheath
      which can be described as a six-start, right-handed helical tubular structure
      with a diameter of about 100 nm, and a pitch of helix of about 260 nm. By
      proteomic, microscopic and immunolabelling analyses, we showed that the sheath of
      MO-1 consists of glycoprotein with an apparent molecular mass > 350 kDa. This
      protein, named sheath-associated protein (Sap), shows homology with bacterial
      adhesins and eukaryotic calcium-dependent adherent proteins (cadherin). Most
      importantly, we showed that calcium ions mediate the assembly of the tubular
      shaped sheath and disintegration of the sheath was deleterious for smooth
      swimming of MO-1 cells. The disintegrated sheath was efficiently reconstituted in
      vitro by adding calcium ions. Altogether, these results demonstrate a novel
      bacterial Ca(2+) -dependent surface architecture, which is essential for
      bacterial swimming.

PMID- 21091514
TI  - Feasibility of nonthermal atmospheric pressure plasma for intracoronal bleaching.
AB  - AIM: To investigate the effect of nonthermal atmospheric pressure plasma on
      intracoronal tooth bleaching in blood stained human teeth. METHODOLOGY: Forty
      extracted single-root and blood stained human teeth were used. The teeth were
      randomly divided into two groups (n=20): group 1 received 30% HP activated by
      nonthermal atmospheric pressure plasma in the pulp chamber for 30 min, whilst
      group 2 received 30% HP alone in the pulp chamber for 30 min. The overall colour
      changes (DeltaE) were assessed using the Commission Internationale de L'Eclairage
      (CIE) Lab Colour System. The data were analysed using Student's t-test to
      determine the significant differences. RESULTS: The temperature of all teeth was
      maintained at approximately 37  degrees C during plasma bleaching. The plasma
      treatment with 30% HP resulted in significantly higher bleaching efficacy
      compared to 30% HP alone in discoloured teeth (P<0.05). The average DeltaE values
      of group 1 and group 2 were 9.24 (0.37) and 4.47 (1.62), respectively, at 30 min.
      CONCLUSIONS: The application of nonthermal atmospheric pressure plasma to
      intracoronal bleaching could be a novel and efficient therapy in the bleaching of
      haemorrhagically stained teeth.

PMID- 21091513
TI  - Chemoreceptors in signalling complexes: shifted conformation and asymmetric
      coupling.
AB  - Bacterial chemotaxis is mediated by signalling complexes of chemoreceptors,
      histidine kinase CheA and coupling protein CheW. Interactions in complexes
      profoundly affect the kinase. We investigated effects of these interactions on
      chemoreceptors by comparing receptors alone and in complexes. Assays of initial
      rates of methylation indicated that signalling complexes shifted receptor
      conformation towards the methylation-on, higher-ligand-affinity, kinase-off
      state, tuning receptors for greater sensitivity. In contrast, transmembrane and
      conformational signalling within chemoreceptors was essentially unaltered,
      consistent with other evidence identifying receptor dimers as the fundamental
      units of such signalling. In signalling complexes, coupling of ligand binding to
      kinase activity is cooperative and the dynamic range of kinase control expanded >
      100-fold by receptor adaptational modification. We observed no cooperativity in
      influence of ligand on receptor conformation, only on kinase activity. However,
      receptor modification generated increased dynamic range in a stepwise fashion,
      partly in coupling ligand to receptor conformation and partly in coupling
      receptor conformation to kinase activity. Thus, receptors and kinase were not
      equivalently affected by interactions in signalling complexes or by ligand
      binding and adaptational modification, indicating asymmetrical coupling between
      them. This has implications for mechanisms of precise adaptation. Coupling might
      vary, providing a previously unappreciated locus for sensory control.

PMID- 21091515
TI  - A strain-based flow-induced hemolysis prediction model calibrated by in vitro
      erythrocyte deformation measurements.
AB  - Hemolysis is caused by fluid stresses in flows within hypodermic needles, blood
      pumps, artificial hearts, and other cardiovascular devices. Developers of
      cardiovascular devices may expend considerable time and effort in testing of
      prototypes, because there is currently insufficient understanding of how flow
      induced cell damage occurs to accurately predict hemolysis. The objective of this
      project was to measure cell deformation in response to a range of flow
      conditions, and to develop a constitutive model correlating cell damage to fluid
      stresses. An experimental system was constructed to create Poiseuille flow under
      a microscope with velocities up to 4 m/s, Reynolds number to 200, and fluid
      stresses to 5000 dyn/cm(2). Pulsed laser illumination and a digital camera
      captured images of cells deformed by the flow. Equilibrium equations were
      developed to relate fluid stresses to cell membrane tension, and a viscoelastic
      membrane model was used to predict cell strain. Measurements of aspect ratio as a
      function of shear stress and duration of shear were used to calibrate the cell
      deformation model. Hemolysis prediction was incorporated with a threshold strain
      value for cell rupture. The new model provides an improved match to
      experimentally observed hemolytic stress thresholds, particularly at long
      exposure times, and may reduce the empiricism of hemolysis prediction.

PMID- 21091516
TI  - Continuous hemodiafiltration in children after cardiac surgery.
AB  - Acute renal failure (ARF) after congenital cardiac surgery remains a serious
      complication and leading cause of morbidity and mortality. Continuous
      hemodiafiltration (CHDF) is presently accepted for pediatric applications. We
      retrospectively evaluated the effects of CHDF against ARF after congenital
      cardiac surgery at our hospital. We analyzed data from seven patients aged 23
      days to 9 years and weighing 1.7-22.4 kg requiring dialysis therapy using CHDF
      after congenital cardiac surgery between April 2002 and January 2009. One patient
      who died could not be weaned from extracorporeal membrane oxygenation support and
      another died of multiple organ failure. Renal function recovered to normal in the
      other five (71%) patients. Treatment by CHDF lasted from 14 to 680 h and net
      ultrafiltration was 3.5 +/- 1.4 mL/kg/h. Serum creatinine and urea concentrations
      were, respectively, 2.3 +/- 1.6 and 43.7 +/- 17.0 mg/dL before, and 0.5 +/- 0.2
      and 13.5 +/- 8.1 mg/dL, after CHDF (P < 0.05). Thrombocytopenia developed in all
      patients, and platelet concentrates (0.76 +/- 0.7 mL/kg/h) were infused during
      CHDF. Hypotension developed after changing the CHDF set in one patient. We
      suggest that CHDF is an effective alternative strategy for treating renal
      dysfunction after congenital cardiac surgery.

PMID- 21091517
TI  - Albumin dialysis without anticoagulation in high-risk patients: an observational
      study.
AB  - Severe liver failure causes coagulopathy and high bleeding risk. Albumin dialysis
      with Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden) is
      useful for treatment. However, anticoagulation during its use is of uncertain
      value. We omitted heparin-saline priming and intradialytic heparin and examined
      its effects. Albumin dialysis was performed in critically ill patients with
      intermittent circuit saline flushes (2664 +/- 2420 mL per treatment). A total of
      12 patients (M : F = 10:2; age 49 +/- 9 years) were thus treated: 6 for fulminant
      hepatic failure and 6 for acute-on-chronic liver failure. The overall
      hospitalization duration was 31 +/- 30 days. A total of 44 treatment sessions
      were performed (average 8 +/- 7 sessions per patient). Prescribed versus achieved
      MARS duration were 13 +/- 3 versus 11 +/- 4 h, P < 0.05. Twenty-three percent
      (10/44) of MARS sessions clotted, 11% (5/44) of treatments were electively
      terminated, and 2% (1/44) developed vascular catheter occlusion. Spontaneous
      bleeding occurred in 9% (4/44). Pre- versus post-MARS systemic and blood circuit
      transmembrane pressures (mm Hg), and albumin dialysate afferent and efferent
      pressures were all stable. Coagulation indices were (pre- vs. post-MARS): (i)
      prothrombin time (seconds): 36 +/- 30 versus 42 +/- 33, P = 0.143; (ii) activated
      partial thromboplastin time (seconds): 78 +/- 43 versus 88 +/- 45, P = 0.117; and
      (iii) platelet count (*10(3) /uL): 87 +/- 40 versus 76 +/- 48, P = 0.004.
      Systemic blood solute concentrations pre- versus post-MARS were: (i) serum urea
      (mg/dL): 22.4 +/- 19.6 versus 14.0 +/- 8.4, P < 0.05; (ii) serum creatinine
      (mg/dL): 2.8 +/- 2.3 versus 1.9 +/- 1.5, P < 0.05; (iii) total bilirubin (mg/dL):
      29.5 +/- 8.8 versus 20.5 +/- 5.1, P < 0.05; and (iv) plasma ammonia (ug/dL): 186
      +/- 85 versus 129 +/- 66, P < 0.05. Anticoagulant-free albumin dialysis remained
      effective despite frequent circuit clotting. This led to significant exacerbation
      of thrombocytopenia although bleeding risk remained low.

PMID- 21091518
TI  - Air-handling capabilities of blood cardioplegia delivery systems in a simulated
      pediatric model.
AB  - Blood cardioplegia delivery systems are employed in most pediatric open heart
      cases to arrest the heart and keep it preserved during aortic cross-clamping.
      They are also used as part of a modified ultrafiltration system at the end of
      cardiopulmonary bypass. We evaluated and compared the air-handling capabilities
      of different types of blood cardioplegia delivery devices. A simple circuit
      incorporating a cardiotomy reservoir, a roller pump, a cardioplegia test system,
      and two emboli detection and classification sensors were used to investigate the
      air-handling capabilities of the following cardioplegia delivery systems: GISH
      Vision, Maquet Plegiox, Medtronic Trillium MYOtherm XP, Sorin Group BCD Vanguard,
      Sorin Group CSC14, and Terumo Sarns Conducer and Bubble Trap. The 0.25-in.
      circuit was primed with 400mL of Lactated Ringer's. Outdated packed red blood
      cells were added to obtain a hematocrit of 24-28%. System pressure was maintained
      at 50mmHg. Air (0.1, 0.3, 0.5mL) was injected at a speed of 0.1mL/s into the
      circuit just after the pump head. Gaseous microemboli (GME) were measured prior
      to the cardioplegia system and after the device to evaluate the air-handling
      characteristics. The tests were run at 100, 200, and 400mL/min blood flow for
      both 4 and 37 degrees C. There were no significant differences among the groups
      when comparing precardioplegia delivery system GME, thus demonstrating that all
      devices received the same amount of injected air. When comparing the groups for
      postcardioplegia delivery system GME, significant differences were noted
      especially at the 400mL/min blood flow rate. These results suggest that for the
      devices compared in this study, the Maquet Plegiox and the Medtronic Trillium
      MYOtherm XP eliminated GME the best.

PMID- 21091519
TI  - Lucinidae/sulfur-oxidizing bacteria: ancestral heritage or opportunistic
      association? Further insights from the Bohol Sea (the Philippines).
AB  - The first studies of the 16S rRNA gene diversity of the bacterial symbionts found
      in lucinid clams did not clarify how symbiotic associations had evolved in this
      group. Indeed, although species-specific associations deriving from a putative
      ancestral symbiotic association have been described (coevolution scenario),
      associations between the same bacterial species and various host species
      (opportunistic scenario) have also been described. Here, we carried out a
      comparative molecular analysis of hosts, based on 18S and 28S rRNA gene
      sequences, and of symbionts, based on 16S rRNA gene sequences, to determine as to
      which evolutionary scenario led to modern lucinid/symbiont associations. For all
      sequences analyzed, we found only three bacterial symbiont species, two of which
      are harbored by lucinids colonizing mangrove swamps. The last symbiont is the
      most common and was found to be independent of biotope or depth. Another
      interesting feature is the similarity of ctenidial organization of lucinids from
      the Philippines to those described previously, with the exception that two
      bacterial morphotypes were observed in two different species (Gloverina
      rectangularis and Myrtea flabelliformis). Thus, there is apparently no specific
      association between Lucinidae and their symbionts, the association taking place
      according to which bacterial species is present in the environment.

PMID- 21091520
TI  - An individual-based approach to explain plasmid invasion in bacterial
      populations.
AB  - We present an individual-based experimental framework to identify and estimate
      the main parameters governing bacterial conjugation at the individual cell scale.
      From this analysis, we have established that transient periods of unregulated
      plasmid transfer within newly formed transconjugant cells, together with contact
      mechanics arising from cellular growth and division, are the two main processes
      determining the emergent inability of the pWW0 TOL plasmid to fully invade
      spatially structured Pseudomonas putida populations. We have also shown that pWW0
      conjugation occurs mainly at advanced stages of the growth cycle and that
      nongrowing cells, even when exposed to high nutrient concentrations, do not
      display conjugal activity. These results do not support previous hypotheses
      relating conjugation decay in the deeper cell layers of bacterial biofilms to
      nutrient depletion and low physiological activity. We observe, however, that
      transient periods of elevated plasmid transfer in newly formed transconjugant
      cells are offset by unfavorable cell-to-cell contact mechanics, which ultimately
      precludes the pWWO TOL plasmid from fully invading tightly packed multicellular
      P. putida populations such as microcolonies and biofilms.

PMID- 21091521
TI  - Assemblages' structure and activity of bacterioplankton in northern Adriatic Sea
      surface waters: a 3-year case study.
AB  - The bacterial community, both in terms of community structure (denaturing
      gradient gel electrophoresis fingerprinting) and activity (exoenzymatic
      hydrolysis of proteins, polysaccharides and phosphorylated molecules and leucine
      uptake), was investigated seasonally for 3 years (2004-2006) in a large-scale
      grid in the northern Adriatic Sea. A high variability characterized the spatial
      structure of bacterial assemblages and a scarce seasonality was found in all the
      nine studied stations. Bacterial communities were substantially diverse in the
      same season of the 3 years, in contrast to what was reported previously for
      oceanic sites. Assemblages were in general strongly affected by river inputs,
      especially in spring, when freshwater loads were higher. Finally, a close
      relationship was found between given assemblages and their patterns of
      degradation/production activities by applying a multivariate analysis (linear
      discriminant analysis) to the dataset. The high variability of bacterial
      community structures and patterns of activity may indicate an ecological response
      to the high dynamism that characterizes the basin both on a physical and on a
      biological basis.

PMID- 21091522
TI  - Prolonged environmental persistence requires efficient disinfection procedures to
      control Devriesea agamarum-associated disease in lizards.
AB  - AIMS: Devriesea agamarum infection causes chronic proliferative dermatitis,
      especially in desert dwelling lizards. The present study was concerned with
      evaluating persistency of D. agamarum in the environment and the evaluation of
      the efficacy of various disinfection procedures. METHODS AND RESULTS: First, the
      survival of D. agamarum was assessed both in dermal crusts obtained from
      clinically and naturally infected lizards, and during periods of prolonged
      nutrient starvation on dry surface, in moist sand and in distilled water.
      Secondly, a modified European Suspension Test was performed to determine the
      efficacy of eight procedures for the disinfection of equipment, environmental
      surfaces and the topical treatment of D. agamarum-associated dermal lesions. The
      bacterium proved to persist and remain viable for up to 57 days in dermal crusts
      and for more than 5months in moist sand and distilled water. In contrast,
      survival on dry surfaces was limited. The results of the described dilution
      neutralization method demonstrated that most of the tested disinfection
      procedures were sufficient in achieving a 5-decimal logarithmic reduction in the
      number of D. agamarum colony-forming units. The use of relatively low
      concentrations of hydrogen peroxide and a boric and peracetic acid solution on
      the other hand resulted in insufficient reduction in viable counts. CONCLUSIONS:
      Devriesea agamarum can persist for long periods of time in the environment,
      especially under moist conditions, making the use of suitable disinfection
      procedures necessary. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      demonstrates the need for a dry environment for most desert lizards and the use
      of effective disinfection procedures next to antimicrobial treatment to eliminate
      D. agamarum-associated disease from captive saurian collections.

PMID- 21091523
TI  - Longitudinal direct medical costs associated with constipation in women.
AB  - BACKGROUND: Although direct medical costs for constipation-related medical visits
      are thought to be high, to date, there have been no studies examining
      longitudinal resource utilisation in adults with constipation. AIM: To estimate
      the incremental direct medical costs associated with constipation in women.
      METHODS: This is a nested case-control study. The study population consisted of
      all mothers of 5718 children in the population-based birth cohort born during
      1976-1982 in a community. The cases presented to the medical facilities with
      constipation. The controls were randomly selected and matched to cases in a 2:1
      ratio. Direct medical costs for constipated women and controls were collected for
      the years 1987-2002. RESULTS: We identified 168 women with a diagnosis of
      constipation. The total direct medical costs over the 15-year period for
      constipated subjects were more than double those of controls [$63 591 (95% CI: 49
      786-81 396) vs. $24 529 (95% CI: 20 667-29 260)]. The overall out-patient costs
      for constipated women were $38 897 (95% CI: 31 381-48 253) compared to $15 110
      (95% CI: 12 904-17 781) for controls. The median of annual out-patient visits for
      constipated women was 0.16 compared to 0.11 for controls. CONCLUSION: Women with
      constipation have significantly higher medical care utilisation and expenditures
      compared with women without constipation.

PMID- 21091524
TI  - Systematic review: medical and nutritional interventions for the management of
      intestinal failure and its resultant complications in children.
AB  - BACKGROUND: Intestinal failure (IF) affects a growing number of children due to
      increasing numbers of preterm infants surviving intestinal resection for
      necrotising enterocolitis and improving surgical techniques for congenital gut
      anomalies. Parenteral nutrition (PN) is the mainstay of therapy; enteral
      nutrition may have trophic effects on the gut. AIM: To review systematically
      evidence for the effectiveness of medical and nutritional interventions in the
      treatment of IF in children. METHODS: Retrieval of data from studies of patients
      aged <18 years and receiving >28 days of PN. Outcome measures were improvement in
      intestinal function, intestinal adaptation, growth, prevention and treatment of
      IF-associated liver disease, and mortality. Cochrane Database (November 2009),
      MEDLINE (1950-November 2009) and CINAHL (1982-November 2009) electronic database
      searches were made using keyword and subject headings (MeSH): IF, Short Bowel
      Syndrome (SBS), PN and Child. The level of the evidence (EL) was assessed using
      SIGN (Scottish Intercollegiate Guidelines Network) methodology
      (http://www.sign.ac.uk). RESULTS: From 1 607 620 hits, 720 abstracts were
      reviewed. Thirty-three original articles were included. No studies were of high
      methodological quality. CONCLUSIONS: The evidence base for medical and
      nutritional interventions in paediatric IF is limited and of poor quality. In the
      absence of randomised-controlled trials, this evidence base can improve through
      case control and cohort research; and with better multiagency communication, the
      study of inter-centre differences is possible. Achievable short-term goals would
      include the study of: optimal ursodeoxycholic usage, novel intralipid
      formulations, cycled enteral antibiotics, enteral probiotics and new enteral
      feeding strategies.

PMID- 21091525
TI  - Associations between school deprivation indices and oral health status.
AB  - BACKGROUND: Despite an overall improvement in oral health status in several
      countries over the past decades, chronic oral diseases (COD) remain a public
      health problem, occurring mostly among children in the lower social strata. The
      use of publicly available indicators at the school level may be an optimal
      strategy to identify children at high risk of COD in order to organize oral
      health promotion and intervention in schools. OBJECTIVE: To investigate whether
      school deprivation indices were associated with schoolchildren oral health
      status. METHODS: This ecological study used a sample of 316 elementary public
      schools in the province of Quebec, Canada. Data from two sources were linked
      using school identifiers: (i) Two school deprivation indices (in deciles) from
      the Ministry of Education, a poverty index based on the low income cut-offs
      established by Statistics Canada and a socioeconomic environment index defined by
      the proportions of maternal under-schooling and of unemployed parents and (ii)
      Oral health outcomes from the Quebec Schoolchildren Oral Health Survey 1998-99
      aggregated at the school level. These included proportions of children with
      dental caries and reporting oral pain. The relation between school deprivation
      indices and oral health outcomes was assessed with linear regression for dental
      caries experience and logistic regression for oral pain. RESULTS: The mean DMF-S
      (mean number of decayed, missing and filled permanent teeth surfaces) by school
      was 0.7 (SD = 0.5); the average proportions of children with dental caries and
      reporting oral pain were 25.0% and 3.0%, respectively. The poverty index was not
      associated with oral health outcomes. For the socioeconomic environment index,
      dental caries experience was 6.9% higher when comparing schools in unfavourable
      socioeconomic environments to the most favourable ones [95% confidence interval
      (CI): 2.1, 11.7%]. Furthermore, the most deprived schools, as compared to least
      deprived ones, were almost three times as likely to have children reporting oral
      pain in the previous week. CONCLUSION: The school socioeconomic environment index
      was associated with oral health outcomes, and should be studied for its potential
      usefulness in planning school-based oral health promotion and screening
      strategies.

PMID- 21091526
TI  - Measurement of social support, community and trust in dentistry.
AB  - BACKGROUND AND AIM: Relationships among people at work have previously been found
      to contribute to the perception of having a good work. The aim of the present
      paper was to develop scales measuring aspects of social support, trust, and
      community among dentists, and to evaluate psychometric properties of the scales.
      MATERIAL AND METHODS: In 2008, a questionnaire was sent to 1,835 general dental
      practitioners randomly selected from the dental associations in Sweden and
      Denmark. The response rate was 68% after two reminders. Principal Component
      Analysis was applied to 14 items and scales were established based on the
      resulting factors. Internal consistency was evaluated by Cronbach's alpha.
      Differential Item Functioning (DIF) with respect to gender, nationality and
      employment sector was analysed using ordinal logistic regression methods.
      Construct validity was assessed in relation to self-rated health and a range of
      work satisfaction outcomes. RESULTS: The percentage of missing values on the
      items was low (range 0.7%-3.8%). Two scales (range 0-100) were established to
      measure 'Community with Trust'(nine items, mean = 79.2 [SD = 13.4], Cronbach's
      alpha = 0.89) and 'Collegial Support'(five items, mean = 70.4 [SD = 20.8],
      Cronbach's alpha = 0.89). DIF of only minor importance was found which supported
      cultural equivalence. The two scales were weakly positively correlated with each
      other. 'Community with Trust' was in general more strongly correlated with work
      satisfaction variables than 'Collegial Support' was. CONCLUSIONS: Stability and
      internal consistency of the scales were considered as satisfactory. Content
      validity and construct validity were considered as good. Further validation in
      other populations is recommended.

PMID- 21091527
TI  - Treatment of peri-implantitis using an Er:YAG laser or an air-abrasive device: a
      randomized clinical trial.
AB  - BACKGROUND: Non-surgical peri-implantitis therapies appear to be ineffective.
      Limited data suggest that ER:YAG laser therapy improves clinical conditions. The
      present study aimed at comparing the treatment effects between air-abrasive (AM)
      and Er:YAG laser (LM) mono-therapy in cases with severe peri-implantitis.
      MATERIALS AND METHODS: Twenty-one subjects in each group were randomly assigned
      to one time intervention by an air-abrasive device or an Er:YAG laser. Clinical
      data were collected before treatment and at 6 months. Data analysis was performed
      using repeat univariate analysis of variance controlling for subject factors.
      RESULTS: No baseline subject characteristic differences were found. Bleeding on
      probing and suppuration decreased in both the groups (p<0.001). The mean probing
      depth (PPD) reductions in the AM and LM groups were 0.9 mm (SD 0.8) and 0.8 mm
      (SD +/- 0.5), with mean bone-level changes (loss) of -0.1 mm (SD +/- 0.8) and 
      0.3 mm (SD +/- 0.9), respectively (NS). A positive treatment outcome, PPD
      reduction >=0.5 mm and gain or no loss of bone were found in 47% and 44% in the
      AM and LM groups, respectively. CONCLUSIONS: The clinical treatment results were
      limited and similar between the two methods compared with those in cases with
      severe peri-implantitis.

PMID- 21091528
TI  - Clinical and radiographic outcomes following non-surgical therapy of periodontal
      infrabony defects: a retrospective study.
AB  - BACKGROUND AND AIM: The aim of this retrospective study was to analyse the
      clinical and radiographic response of infrabony defects following non-surgical
      therapy and to detect the factors associated with such a response. MATERIALS AND
      METHODS: Clinical and radiographic data were retrieved from 143 consecutive
      patients treated with non-surgical periodontal therapy and re-assessed by the
      same clinician. Linear radiographic measurements of infrabony periodontal defects
      were performed on baseline and follow-up (12-18 months post-treatment)
      radiographs. Multilevel analysis was performed to analyse the associations
      between subject and site factors and healing of infrabony defects. RESULTS: A
      total of 126 infrabony defects from 68 of these patients were identified at
      baseline and included in the analysis. Statistically significant reductions in
      probing pocket depth, clinical attachment loss, radiographic defect depth and a
      widening of the radiographic infrabony defect angle were detected following
      treatment. Initial defect depth and use of adjunctive antibiotics were positively
      associated with a reduction of radiographic defect depth, whereas smoking showed
      a negative association. CONCLUSIONS: Within the limitations of a retrospective
      analysis with no control group, this study shows favourable clinical and
      radiographic outcomes in periodontal infrabony defects following non-surgical
      therapy, with complete bone fill in some cases.

PMID- 21091530
TI  - Marinitalea sucinacia gen. nov., sp. nov., a marine bacterium of the family
      Flavobacteriaceae isolated from tidal flat sediment.
AB  - An amber-pigmented, Gram-negative, rod-shaped and aerobic bacterial strain devoid
      of flagella, designated strain JC2131(T) , was isolated from tidal flat sediment
      of Dongmak in Ganghwa island, South Korea. Identification was carried out on the
      basis of polyphasic taxonomy. Phylogenetic analysis based on the 16S rRNA gene
      sequence revealed that the isolate belonged to the family Flavobacteriaceae and
      showed the highest sequence similarity of 94.5% with Lutibacter litoralis KCCM
      42118(T). The predominant cellular fatty acids were iso-C(15:0) (25.9%), iso
      C(15:0) 3-OH (20.0%) and iso-C(13:0) (12.7%). Flexirubin-type pigments were
      absent. The major isoprenoid quinone was MK-6. The DNA G+C content was 43.7 mol%.
      Several phenotypic and chemotaxonomic properties including growth at pH 6, sea
      salts requirement, aesculin hydrolysis, carbon utilization, DNA G+C content and
      fatty acid profiles also differentiated the strain from the related members of
      the family. Therefore, results from the polyphasic taxonomy study suggested that
      strain JC2131(T) represents a novel genus and species in the family
      Flavobacteriaceae for which the name Marinitalea sucinacia gen. nov., sp. nov. is
      proposed (type strain JC2131(T)=KCTC 12705(T)=JCM 14003(T)).

PMID- 21091529
TI  - Factors related to prosthetic restoration in patients with shortened dental
      arches: a multicentre study.
AB  - The aim of this study was to identify the factors related to prosthetic
      restoration in patients with shortened dental arches (SDA). SDA patients with 2
      12 missing occlusal units were consecutively enrolled from seven university-based
      dental hospitals in Japan. Of the 145 subjects (mean age; 63.4 years), 41% chose
      no treatment and 59% sought to replace their edentulous spaces with removable
      partial dentures or implant-supported fixed partial dentures. Restoration
      decisions were related to tooth loss patterns. Only 3% of subjects missing just
      second molar(s) sought to receive prosthetic treatment, while the percentage
      increased to 58% in subjects who were missing first and second molars and 93% in
      subjects missing premolar(s). Logistic regression analyses found that young age,
      increased number of missing occlusal units, asymmetric arch and presence of
      chewing complaint were significant predictors for prosthetic restoration
      (P<0.05). Increased number of missing occlusal units and asymmetric arch were
      significant predictors for the presence of chewing complaint (P<0.05). These
      results suggest that perceived impairment of chewing ability owing to missing
      occlusal units is a critical factor for prosthetic restoration in SDA patients.

PMID- 21091531
TI  - Streptococcus fryi sp. nov., a novel species with Lancefield group M antigens.
AB  - The taxonomic characteristics of beta-hemolytic streptococcal strains that
      reacted with Lancefield group M antisera were investigated. Group M streptococci
      have not been proposed as a species to date. Four strains of the group M
      streptococci isolated from dog were located within the pyogenic group of the
      genus Streptococcus on 16S rRNA gene-based phylogenetic analysis; the group M
      strains were located a short distance away from all other members of the group.
      The homology values of 16S rRNA gene sequences between group M strains and all
      other streptococci were<95.6%. Group M strains exhibited low levels of DNA-DNA
      homology to other streptococcal species. Some biochemical traits, such as beta
      galactosidase activity and acid production from glycogen, could distinguish these
      group M strains from other closely related species. Thus, these strains are
      proposed to constitute a new species -Streptococcus fryi sp. nov. The type strain
      is PAGU 653(T) (=NCTC 10235(T)=JCM 16387(T)).

PMID- 21091532
TI  - Novel lytic bacteriophages from soil that lyse Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is a Gram-negative saprophytic bacterium that causes
      severe sepsis with a high mortality rate in humans and a vaccine is not
      available. Bacteriophages are viruses of bacteria that are ubiquitous in nature.
      Several lysogenic phages of Burkholderia spp. have been found but information is
      scarce for lytic phages. Six phages, ST2, ST7, ST70, ST79, ST88 and ST96, which
      lyse B. pseudomallei, were isolated from soil in an endemic area. The phages
      belong to the Myoviridae family. The range of estimated genome sizes is 24.0-54.6
      kb. Phages ST79 and ST96 lysed 71% and 67% of tested B. pseudomallei isolates and
      formed plaques on Burkholderia mallei but not other tested bacteria, with the
      exception of closely related Burkholderia thailandensis which was lysed by ST2
      and ST96 only. ST79 and ST96 were observed to clear a mid-log culture by lysis
      within 6 h when infected at a multiplicity of infection of 0.1. As ST79 and ST96
      phages effectively lysed B. pseudomallei, their potential use as a biocontrol of
      B. pseudomallei in the environment or alternative treatment in infected hosts
      could lead to benefits from phages that are available in nature.

PMID- 21091533
TI  - Variations in spa types found in consecutive MRSA isolates from the same
      patients.
AB  - Very little is known about how the spa gene mutates over time in methicillin
      resistant Staphylococcus aureus (MRSA) from the same patient. Copenhagen is an
      area with low prevalence of MRSA but with high variability in spa types. We
      collected 1536 MRSA isolates from 319 patients during a 5-year period and found
      spa type alterations in 30 MRSA isolates (2%) from 13 patients (4%). The
      alteration most often seen was the deletion of repeats followed by repeat
      duplication and point mutation.

PMID- 21091534
TI  - Nursing assessment during oxygen administration in ventilated preterm infants.
AB  - AIM: To document nurses' opinions about their assessments of oxygen requirements
      in ventilated preterm infants receiving oxygen supplementation. METHODS: Survey
      design with descriptive statistics. The sample consisted of 111 nurses employed
      in clinical positions in neonatal intensive care units within Norway's five
      regional hospitals. The questionnaire included questions about physiological and
      clinical observations used when assessing oxygen administration in ventilated
      preterm infants. RESULTS: A major finding was the gap between the criteria laid
      down in professional and research literature, vs the criteria nurses perceived
      they were using when they assessed the oxygen requirements of preterm infants.
      The respondents stated that they used oxygen saturation to assess the infants'
      oxygen requirements when adjusting oxygen supplementation. Only 17% of the nurses
      used the oxygen-haemoglobin dissociation curve in their assessments. Those who
      responded that they used the curve did not use it correctly. CONCLUSION:
      Assessment of O2 requirement is based on insufficient information and calls for
      evaluation of local, national as well as international education. Close
      collaboration between doctors and nurses is essential in planning care for
      individual patients.

PMID- 21091535
TI  - How optometrists record corneal staining.
AB  - PURPOSE:   The aim of this study was to determine current approaches adopted by
      optometrists to the recording of corneal staining following fluorescein
      instillation. METHODS:   An anonymous 'record-keeping task' was sent to all 756
      practitioners who are members of the Queensland Division of Optometrists
      Association Australia. This task comprised a form on which appeared a colour
      photograph depicting contact lens solution-induced corneal staining. Next to the
      photograph was an empty box, in which practitioners were asked to record their
      observations. Practitioners were also asked to indicate the level of severity of
      the condition at which treatment would be instigated. RESULTS:   Completed task
      forms were returned by 228 optometrists, representing a 30 per cent response
      rate. Ninety-two per cent of respondents offered a diagnosis. The most commonly
      used descriptive terms were 'superficial punctate keratitis' (36 per cent of
      respondents) and 'punctate staining' (29 per cent). The level of severity and
      location of corneal staining were noted by 69 and 68 per cent of respondents,
      respectively. A numerical grade was assigned by 44 per cent of respondents. Only
      three per cent nominated the grading scale used. The standard deviation of
      assigned grades was +/- 0.6. The condition was sketched by 35 per cent of
      respondents and two per cent stated that they would take a photograph of the eye.
      Ten per cent noted the eye in which the condition was being observed. Opinions of
      the level of severity at which treatment for corneal staining should be
      instigated varied considerably between practitioners, ranging from 'any sign of
      corneal staining' to 'grade 4 staining'. CONCLUSION:   Although most
      practitioners made a sensible note of the condition and properly recorded the
      location of corneal staining, serious deficiencies were evident regarding other
      aspects of record-keeping. Ongoing programs of professional optometric education
      should reinforce good practice in relation to clinical record-keeping.

PMID- 21091536
TI  - Clinical and experimental links between diabetes and glaucoma.
AB  - Glaucoma is a leading cause of blindness. It is a multifactorial condition, the
      risk factors for which are increasingly well defined from large-scale
      epidemiological studies. One risk factor that remains controversial is the
      presence of diabetes. It has been proposed that diabetic eyes are at greater risk
      of injury from external stressors, such as elevated intraocular pressure.
      Alternatively, diabetes may cause ganglion cell loss, which becomes additive to a
      glaucomatous ganglion cell injury. Several clinical trials have considered
      whether a link exists between diabetes and glaucoma. In this review, we outline
      these studies and consider the causes for their lack of concordant findings. We
      also review the biochemical and cellular similarities between the two conditions.
      Moreover, we review the available literature that attempts to answer the question
      of whether the presence of diabetes increases the risk of developing glaucoma. At
      present, laboratory studies provide robust evidence for an association between
      diabetes and glaucoma.

PMID- 21091537
TI  - No racial difference in allele frequencies of FCGR3A gene F158V polymorphisms in
      diffuse large B-cell lymphoma.

PMID- 21091538
TI  - Bio-Oss collagen in the buccal gap at immediate implants: a 6-month study in the
      dog.
AB  - BACKGROUND: following tooth extraction and immediate implant installation, the
      edentulous site of the alveolar process undergoes substantial bone modeling and
      the ridge dimensions are reduced. objective: the objective of the present
      experiment was to determine whether the process of bone modeling following tooth
      extraction and immediate implant placement was influenced by the placement of a
      xenogenic graft in the void that occurred between the implant and the walls of
      the fresh extraction socket. MATERIAL AND METHODS: five beagle dogs about 1 year
      old were used. The 4th premolar in both quadrants of the mandible ((4) P(4) )
      were selected and used as experimental sites. The premolars were hemi-sected and
      the distal roots removed and, subsequently, implants were inserted in the distal
      sockets. In one side of the jaw, the marginal buccal-approximal void that
      consistently occurred between the implant and the socket walls was grafted with
      Bio-Oss Collagen while no grafting was performed in the contra-lateral sites.
      After 6 months of healing, biopsies from each experimental site were obtained and
      prepared for histological analyses. RESULTS: the outline of the marginal hard
      tissue of the control sites was markedly different from that of the grafted
      sites. Thus, while the buccal bone crest in the grafted sites was comparatively
      thick and located at or close to the SLA border, the corresponding crest at the
      control sites was thinner and located a varying distance below SLA border.
      CONCLUSIONS: it was demonstrated that the placement of Bio-Oss Collagen in the
      void between the implant and the buccal-approximal bone walls of fresh extraction
      sockets modified the process of hard tissue healing, provided additional amounts
      of hard tissue at the entrance of the previous socket and improved the level of
      marginal bone-to-implant contact.

PMID- 21091539
TI  - Socket grafting with the use of autologous bone: an experimental study in the
      dog.
AB  - BACKGROUND: studies in humans and animals have shown that following tooth removal
      (loss), the alveolar ridge becomes markedly reduced. Attempts made to counteract
      such ridge diminution by installing implants in the fresh extraction sockets were
      not successful, while socket grafting with anorganic bovine bone mineral
      prevented ridge contraction. AIM: to examine whether grafting of the alveolar
      socket with the use of chips of autologous bone may allow ridge preservation
      following tooth extraction. METHODS: in five beagle dogs, the distal roots of the
      third and fourth mandibular premolars were removed. The sockets in the right or
      the left jaw quadrant were grafted with either anorganic bovine bone or with
      chips of autologous bone harvested from the buccal bone plate. After 3 months of
      healing, biopsies of the experimental sites were sampled, prepared for buccal
      lingual ground sections and examined with respect to size and composition.
      RESULTS: it was observed that the majority of the autologous bone chips during
      healing had been resorbed and that the graft apparently did not interfere with
      socket healing or processes that resulted in ridge resorption. CONCLUSION:
      autologous bone chips placed in the fresh extraction socket will (i) neither
      stimulate nor retard new bone formation and (ii) not prevent ridge resorption
      that occurs during healing following tooth extraction.

PMID- 21091540
TI  - Effect of socket preservation therapies following tooth extraction in non-molar
      regions in humans: a systematic review.
AB  - OBJECTIVE: To assess, based on the existing literature, the benefit of socket
      preservation therapies in patients with a tooth extraction in the anterior or
      premolar region as compared with no additional treatment with respect to bone
      level. MATERIAL AND METHODS: MEDLINE-PubMed and the Cochrane Central Register of
      controlled trials (CENTRAL) were searched till June 2010 for appropriate studies,
      which reported data concerning the dimensional changes in alveolar height and
      width after tooth extraction with or without additional treatment like
      bonefillers, collagen, growth factors or membranes. RESULTS: Independent
      screening of the titles and abstracts of 1918 MEDLINE-PubMed and 163 Cochrane
      papers resulted in nine publications that met the eligibility criteria. In
      natural healing after extraction, a reduction in width ranging between 2.6 and
      4.6 mm and in height between 0.4 and 3.9 mm was observed. With respect to socket
      preservation, the freeze-dried bone allograft group performed best with a gain in
      height, however, concurrent with a loss in width of 1.2 mm. CONCLUSION: Data
      concerning socket preservation therapies in humans are scarce, which does not
      allow any firm conclusions. Socket preservation may aid in reducing the bone
      dimensional changes following tooth extraction. However, they do not prevent bone
      resorption because, depending on the technique, on the basis of the included
      papers one may still expect a loss in width and in height.

PMID- 21091541
TI  - Effect of heat stress on endotoxin flux across mesenteric-drained and portal
      drained viscera of dairy goat.
AB  - This study was designed to evaluate the effect of heat stress on endotoxin flux
      across mesenteric-drained and portal-drained viscera of dairy goats. Three Saanen
      first lactation dairy goats were surgically fitted with indwelling catheters in
      the portal vein, the mesenteric vein and carotid, and were kept in thermal
      neutral and then heat stress environment, for examining the effect of heat stress
      on endotoxin absorption and redox status. Average net absorption of endotoxin
      (EU/h) across mesenteric-drained viscera (MDV) and portal-drained viscera (PDV)
      during the whole period of heat stress increased by 279.05% and 227.92% in
      relation to thermo-neutral period. Plasma concentration of glutathione peroxidase
      (GSH-Px) and catalase (CAT) in mesenteric and portal vein, and that of superoxide
      dismutase (SOD) in mesenteric vein, increased significantly during heat stress.
      Main conclusions were: (i) net absorption of endotoxin in portal vein is mainly
      from non-mesenteric tissues both in heat stress and in thermo-neutral condition;
      (ii) heat stress may lead to the significant decrease in plasma SOD, GSH-Px, CAT
      flux across PDV and MDV, and the significant increase in endotoxin flux across
      PDV and MDV; and (iii) the increase in gastrointestinal permeability in dairy
      goats during heat stress may not be induced by the increase in oxidative stress.

PMID- 21091542
TI  - Fasting and refeeding modulate the expression of stress proteins along the
      gastrointestinal tract of weaned pigs.
AB  - The gastrointestinal tract (GIT) of young mammals is submitted to aggressions
      early in life and GIT stress proteins are up-regulated in pigs following weaning.
      We hypothesized that transient food deprivation may contribute to these changes.
      Therefore, the effects of fasting and refeeding on GIT stress proteins in weaned
      pigs were investigated. A complete block experimental design with three groups of
      five pigs each was set up with the following treatments: A - food offered, B -
      fasted for 1.5 days, C - fasted for 1.5 days and then re-fed for 2.5 days. After
      slaughter, the GIT was removed, weighed and sampled. Intestinal villi and crypts
      were measured and alkaline phosphatase activity was determined. GIT tissue stress
      protein concentrations were measured by Western blotting. Fasting led to
      intestinal mucosa and villous-crypt atrophy (p < 0.01) and reduced mucosal
      alkaline phosphatase total activity in the proximal small intestine (p < 0.05).
      Heat shock proteins HSP 27 and HSP 90 (but not HSP 70) and neuronal NO synthase
      (nNOS) increased (p < 0.01) in the stomach, mid-intestine and proximal colon with
      fasting. Inducible NOS (iNOS) did so in the stomach (p < 0.001). Refeeding
      partially or totally restored GIT characteristics and stress protein
      concentrations, except for gastric HSP 90 and iNOS. Significant correlations (p <
      0.05 to p < 0.0001) were found among stress proteins, between nNOS and digesta
      weight, between HSP 27 or HSP 90 and intestinal mucosa weight, and between
      intestinal or colonic HSP or nNOS and alkaline phosphatase. In conclusion,
      fasting and refeeding modulate GIT HSP proteins and nNOS in pigs following
      weaning. Changes in digesta and intestinal mucosa weights and alkaline
      phosphatase activity may be involved in the modulation of stress proteins along
      the GIT.

PMID- 21091543
TI  - Effects of starch and fibre in pelleted diets on nutritional status of mule deer
      (Odocoileus hemionus) fawns.
AB  - To compare the effects of a low-starch, high-fibre diet [LSHF; 51.6% neutral
      detergent fibre (NDF), 3.0% starch, 14.8% crude protein (CP)] and a high-starch,
      low-fibre diet (HSLF; 33.3% NDF, 20.0% starch, 19.6% CP) on the nutritional
      status of captive exotic ruminants, 16 mule deer (Odocoileus hemionus) were fed
      one of these two diets ad libitum with <=25% alfalfa hay cubes from 10 days to 68
      weeks of age. During five sampling periods beginning in November and spaced 6-12
      weeks apart thereafter, feed intake, rumen and blood chemistry, faecal scores,
      growth and body condition were measured. Dry matter intake, digestible energy
      intake, time spent ruminating and feeding and blood acetate concentration were
      greater for deer fed LSHF (p < 0.05 for all). Lower dietary CP led to reduced
      blood urea nitrogen for deer consuming LSHF (p = 0.004). Deer had the same faecal
      scores, growth and body fat among treatments (all p > 0.05). These findings show
      pelleted diets with less starch, more fibre, and reduced protein met the energy
      and protein requirements of growing mule deer, a medium-sized browsing ruminant,
      as well as traditional grain-based diets while more closely mimicking natural
      forages and stimulating a more natural feeding behaviour.

PMID- 21091544
TI  - Water intake in domestic rabbits (Oryctolagus cuniculus) from open dishes and
      nipple drinkers under different water and feeding regimes.
AB  - Rabbits (Oryctolagus cuniculus) are often presented suffering from urolithiasis.
      A high water intake is important in the prophylaxis of uroliths. We investigated
      the influence factors for water intake using 12 rabbits subjected to different
      feed and water regimes with practical relevance: Hay, fresh parsley, a seed mix
      and two different pelleted feed were offered in diverse combinations. Water was
      provided either by open dish or nipple drinker. Water was accessible ad libitum
      except for four treatments with 6 h or 12 h water access. Under the different
      feeding regimes, the drinker had no influence on water intake, but faecal dry
      matter content was significantly higher with nipple drinkers [60.0 +/- 2.1 vs.
      57.2 +/- 2.1% of wet weight (mean +/- 95% confidence interval), p = 0.003]. Dry
      food led to a higher drinking water intake but total water intake was still lower
      than with addition of 'fresh' food. With restricted water access, rabbits
      exhibited a significantly higher water intake with open dishes compared with
      nipple drinkers (54.9 +/- 9.8 vs. 48.1 +/- 8.2 g/kg(0.75) /day (mean +/- 95%
      confidence interval), p = 0.04). High proportions of fresh parsley or hay in the
      diet enhanced total water intake and urine output, and led to lower urinary dry
      matter content and lower urinary calcium concentrations. Restricted access to
      drinkers led to a decreased total daily water intake and increased dry matter
      content of urine and faeces. For optimal water provision and urolith prophylaxis,
      we recommend a diet with a high 'fresh food' proportion as well as additionally
      hay ad libitum with free water access, offered in an open bowl.

PMID- 21091545
TI  - Effect of dietary fish oil on milk yield, fatty acids content and serum metabolic
      profile in dairy cows.
AB  - The aim of the study was to evaluate the effects of dietary unprotected fish oil
      on milk yield, fatty acids content and serum metabolic profile in dairy cows.
      Forty lactating Polish Holstein-Friesian cows were assigned to two groups. The
      cows were fed a control basal diet (C group), or a basal diet containing 2%
      addition of fish oil on mineral carrier (FOM group) during a 8-week period.
      Supplementing FOM diet of dairy cows had no significant effect on milk fat, milk
      protein, milk lactose concentration and somatic cells count, but increased the
      milk yield (36.5 kg/d), (p < 0.05) compared with the control cows (34.28 kg/d).
      We observed an increase (p < 0.05) in body condition scoring between C and FOM
      groups. Additionally, higher levels of non-esterified fatty acids and beta
      hydroxybutyrate acid were noticed in FOM group after 8 weeks of the experiment;
      however, these serum parameters still were in the reference range. Concentration
      of insulin was higher (30.40 MUU/ml; p < 0.01) in the FOM group compared with the
      control group (14.03 MUU/ml). In the FOM group, significant increase (p < 0.01)
      in long-chain fatty acids, mainly cis-9, trans-11 CLA and n-3 fatty acids
      (eicosapentaenoic and docosahexaenoic acids) was observed. The obtained results
      demonstrated that addition of fish oil to cows' diet could profitably modify the
      fatty acids in cow's milk.

PMID- 21091546
TI  - Effect of dietary supplementation of probiotic on the performance of F1 crossbred
      (Rhode Island red male * Fayoumi female) cockerels.
AB  - A study was conducted to evaluate four different probiotic levels, using diets
      supplemented with 0 (control), 0.1%, 0.2%, 0.3% or 0.5% of organic-green culture
      zs (probiotic). The cockerels of 6-weeks old were randomly divided into 15
      separate floor pens each comprising 25 birds and three pens (replicates) per
      treatment group following completely randomized design. At 12 weeks of age BW and
      feed to gain ratio (FCR) were determined. At the end of 42 days of experiment,
      nine birds per treatment were sacrificed to evaluate carcass characteristics,
      abdominal fat contents and the internal organs. Blood haemato-biochemical
      parameters were also determined. Haemagglutination inhibition antibody titres
      against Newcastle disease virus and lymphoid organs weight/body weight ratio were
      also determined. The BW of birds fed 0.2-0.5% of probiotic was significantly
      greater than birds fed without probiotic diet. Similarly, better FCR was observed
      in birds those fed diets of high level of probiotic. There was no mortality
      recorded at higher levels of probiotics. Differences in carcass characteristics,
      organs weight, meat composition, haematological values and HDL and LDL
      concentrations among all the diets were non-significant. However, abdominal fat
      contents reduced significantly in supplemented groups in relation to control and
      cholesterol contents were reduced significantly in 0.3% or 0.5% supplemented
      groups in relation to control. Feeding levels of 0.2-0.5% of probiotic, did
      positively affect the immune system within the parameters measured. It may be
      concluded that performance, blood chemistry and immunity against disease in
      cockerels could be maintained when supplementing 0.3% or 0.5% level of probiotic
      incorporated in crossbred cockerel's diets.

PMID- 21091547
TI  - Effects of vitamin C supplementation on growth performance and antioxidant status
      of layer ducklings.
AB  - The study was conducted to evaluate the effects of increasing dietary vitamin C
      supplements on growth performance, antioxidant status and humoral immunity of
      layer ducklings. The results showed that the body weight and daily body weight
      gain of ducklings increased (p < 0.05) with increasing dietary vitamin C
      supplementations and reached a maximum at 400 mg vitamin C/kg feed. The dietary
      vitamin C supplementations reduced the malondialdehyde concentration (p < 0.05)
      and increased the activities of superoxide dismutase and glutathione peroxidase
      (p < 0.05) in serum and liver of ducklings at day 5 and 28. Additionally, feeding
      400 mg/kg or 800 mg vitamin C/kg feed increased IgM and IgA concentrations in
      sera (p < 0.05) and serum IgG concentrations increased (p < 0.05) following
      supplementation in concentrations of 150-800 mg vitamin C/kg feed. In conclusion,
      the results suggested that dietary vitamin C supplements of 400 mg/kg feed
      provide optimal effects on growth performance, antioxidant status and parameters
      of humoral immunity.

PMID- 21091548
TI  - Haematology, blood biochemistry and tissue histopathology of lambs maintained on
      diets containing an insect controlling protein (Cry1Ac) in Bt-cottonseed.
AB  - This experiment assessed the effect of feeding genetically modified cottonseed
      (Bt) containing an insect controlling protein (Cry1Ac) on haematology, blood
      biochemistry and histopathology of lambs. Haemato-biochemicals were estimated at
      periodic intervals, and histopathology at termination of experiment. Thirty three
      weaner lambs were fed a composite feed mixture (CFM) ad libitum individually, in
      three groups for 123 days. The isonitrogenous CFM had roughage (Perl Millet
      Stover) and concentrate ratio of 350:650. Diet fed to control lambs contained
      groundnut oil meal as protein source while other two groups received diet
      containing either whole cottonseed (N-Bt) or Bt-cottonseed (Bt-CS). Daily feed
      intake and average daily gain were similar among lambs of three groups. Lambs fed
      N-Bt diet had higher (p < 0.05) serum protein and globulin compared to control
      and Bt diets, while albumin content was higher (p = 0.018) in Bt diet fed lambs.
      Serum urea and creatinin content, alkaline phosphatase (ALP) and serum glutamate
      pyruvic transaminase (SGPT) activities were not different among lamb groups,
      while urea and creatinin content and ALP activities increased linearly (p <
      0.001) with increased feeding period. Blood haemoglobin (Hb), haematocrit (Hc),
      white blood cells (WBC), mean corpuscular volume (MCV) and mean corpuscular
      haemoglobin concentration (MCHC) ranged from 11.1% to 11.2%, 31.8% to 32.8%, 7.0
      to 8.3 (* 10(3) /MUl), 19.1 to 22.5 fl and 33.2% to 35.5%, respectively, were
      similar among lamb groups. Erythrocyte sedimentation rate (ESR) (p = 0.008) and
      red blood cell counts (p = 0.006) were higher in Bt diet fed lambs. Control and N
      Bt diet fed lambs had mild fatty infiltration in liver and/or micro-calculi in
      renal cortex, and such lesions were not seen in Bt diet fed lambs. Growth,
      haemato-biochemical and histopathology did not change by Bt-CS feeding in growing
      lamb. However, before recommending the use of Bt-CS in routine feed formulations
      prolonged feeding experiments of Bt-cotton seed require.

PMID- 21091549
TI  - Influence of induced heat stress on HSP70 in buffalo lymphocytes.
AB  - Heat stress in farm animals, such as cattle and buffalo during summer and post
      summer seasons is a problem for livestock producers. The effect of heat stress
      becomes pronounced when heat stress is accompanied with ambient humidity
      impairing the immune status, growth, production and reproductive performance of
      animals. Increase in HSP70 levels from cell cultures in presence of different
      stressors often does not reflect the physiological adaptability of animals
      governing thermal regulation. In this study we directly compared the effect of
      different heat stress conditions with the immune status and HSP70 expression
      patterns from buffalo lymphocytes both in vivo and in vitro. Murrah buffalo
      calves were exposed to induced heat stress with two experimental treatments: hot
      dry (42  degrees C with existing relative humidity) or hot humid (35  degrees C
      with 70% relative humidity) condition in psychometric chamber, 4 h daily for 12
      days and compared with control animals maintained in an experimental shed under
      natural conditions. There was >200-fold increase in serum-HSP70 levels in both
      heat stress conditions compared with control. Furthermore, the immune status of
      the calves failed to activate the level of HSP70 expression in serum lymphocytes.
      Lymphocytes cultured in vitro at higher temperature exert 2.5-fold increase in
      HSP70 concentration. This study is the first of its kind to demonstrate more
      complex expression pattern of buffalo serum-HSP70 level as a thermo adaptive
      response compared with in vitro treated cells. Results from this study indicate
      that serum-HSP70 levels could be used as a sensitive biomarker for heat stress
      management in large farm animals.

PMID- 21091550
TI  - Intake, selection, digesta retention, digestion and gut fill of two coprophageous
      species, rabbits (Oryctolagus cuniculus) and guinea pigs (Cavia porcellus), on a
      hay-only diet.
AB  - A colonic separation mechanism (CSM) is the prerequisite for the digestive
      strategy of coprophagy. Two different CSM are known in small herbivores, the
      'wash-back' CSM of lagomorphs and the 'mucous-trap' CSM of rodents. Differences
      between these groups in their digestive pattern when fed exclusively hay were
      investigated in six rabbits (Oryctolagus cuniculus) and six guinea pigs (Cavia
      porcellus). Intake, digestibility (by total faecal collection), solute and
      particle mean retention times (MRT, using Co-EDTA and Cr-mordanted fibres) were
      measured. Rabbits selected less fibrous parts of the hay than guinea pigs,
      leaving orts with higher content of neutral detergent fibre [NDF; 721 +/- 21 vs.
      642 +/- 31 g/kg dry matter (DM) in guinea pigs]. They also expressed a lower NDF
      digestibility (0.44 +/- 0.10 vs. 0.55 +/- 0.05 of total), a similar particle MRT
      (15 +/- 3 vs. 18 +/- 6 h), a longer solute MRT (51 +/- 9 vs. 16 +/- 4 h), and a
      lower calculated dry matter gut fill (19.6 +/- 4.7 vs. 29.7 +/- 4.1 g DM/kg body
      mass) than guinea pigs (p < 0.05 for each variable). These results support the
      assumption that the 'wash-back' CSM, exhibited in the rabbits, is more efficient
      in extracting bacterial matter from the colonic digesta plug than the 'mucous
      trap' CSM found in the guinea pigs. Related to metabolic body mass, rabbits
      therefore need a less capacious colon for their CSM where a more efficient
      bacteria wash-out is reflected in the lower fibre digestibility. A lighter
      digestive tract could contribute to a peculiarity of lagomorphs: their ability to
      run faster than other similar-sized mammals.

PMID- 21091551
TI  - Characterization of ruminal dynamics in Holstein dairy cows during the
      periparturient period.
AB  - We used four pregnant Holstein cows to delineate ruminal adaptations as cows
      transitioned from one lactation to the next. Cows were fed typical diets through
      far-off and close-up dry periods and lactation. We measured ruminal
      characteristics on day 72 (late lactation), 51 (far-off dry), 23 and 9 (close-up
      dry) prepartum and on days 6, 20, 34, 48, 62, 76 and 90 postpartum (early
      lactation). Measurements included: ruminal fill (weight of actual contents),
      ruminal capacity (volume of rumen when fully filled), digestibilities and ruminal
      passage rates. Ruminal capacity tended to increase linearly during early
      lactation but was stable during dry and transition periods. Both total and liquid
      fill decreased linearly during the dry period, increased across parturition, and
      increased linearly through early lactation. Dry matter fill decreased as cows
      were fed the close-up diet at day 23 prepartum then increased near parturition
      and continued to increase across early lactation. Solid passage rate was greatest
      when cows were fed the close-up diet, and decreased throughout the transition
      period. In lactation, solid passage rate responded quadratically with peak at day
      48 followed by decreases through day 90 postpartum. Liquid passage increased
      linearly across the transition period. Total tract organic matter digestibilities
      increased linearly over the dry period with significant increases prior to or
      immediately after parturition, then they remained relatively stable over early
      lactation until they increased at day 90. Fibre digestibilities demonstrated
      quadratic responses over early lactation, being higher on day 6 and day 90 than
      at other times. Starch digestibilities decreased linearly across both the dry and
      transition periods with decreases in lactation until day 62 followed by increases
      until day 90. High producing lactating dairy cows go through a multitude of
      ruminal adaptations, in terms of digestion, passage, capacity and fill, as they
      transition from one lactation to the next.

PMID- 21091552
TI  - Chemical composition and nutritive value of four varieties of cassava leaves
      grown in South-Western Nigeria.
AB  - The nutritive value of leaves of four varieties of cassava - MS 6, TMS 30555,
      Idileruwa and TMS 30572 was evaluated based on their chemical composition and in
      vitro fermentation. Crude protein (CP) contents of cassava leaves ranged from 177
      to 240 g/kg dry matter (DM), with TMS 30555 showing the highest CP contents.
      Neutral detergent fibre (NDFom) and acid detergent fibre (ADFom) contents of
      cassava leaves ranged from 596 to 662 and 418 to 546 g/kg DM respectively.
      Condensed tannin (CT) and hydrocyanic acid contents ranged from 1.0 to 3.8 g/kg
      and 58.5 to 86.7 mg/kg DM respectively. The range of volatile fatty acids (VFA)
      in the supernatant after in vitro incubation of the cassava varieties was:
      acetate (14.7-31.5 mmol/l); propionate (4.5-6.3 mmol/l); butyrate (3.1-3.9
      mmol/l); valerate (0.4-0.6 mmol/l); iso-butyrate (0.6-1.3 mmol/l); iso-valerate
      (1.1-1.9 mmol/l). The acetate:propionate ratio resulting from fermentation of TMS
      30555 was higher(p < 0.05) than that of the other leaves. The highest in vitro
      gas production of 50.5 ml/200 mg DM was recorded for MS6 being higher (p < 0.05)
      than for TMS 30572, but similar to TMS 30555 and Idileruwa. The DM, CP, ADF and
      HCN contents of cassava leaves were positively correlated with gas production,
      while CT content was negatively correlated with gas production. The study showed
      that leaves of the varieties MS 6 and TMS 30555 are superior to the others in
      terms of CP and gas production indicating a higher digestibility and energy
      content and thus nutritive potential. They may therefore serve as supplements for
      ruminants fed on poor roughages.

PMID- 21091553
TI  - Long-term outcome of highly sensitized African American patients transplanted
      with deceased donor kidneys.
AB  - Undertaking transplantation in highly sensitized African American (AA) patients
      as transplant recipients represents a unique challenge. We retrospectively
      compared the outcomes of AA with non-African American (NAA) patients who had
      panel reactive antibody >80% and received deceased donor (DD) kidneys by virtual
      crossmatch. Immunosuppressive regimen included basiliximab induction and
      tacrolimus, mycophenolate acid and steroids maintenance. Among 835 consecutive
      transplants from 1998 to 2007, 142 (17%) were sensitized patients including 89
      (16.6%) AA and 53 (17.7%) NAA patients. The AA group had similar 5-year incidence
      of acute rejection as NAA group (21.4% vs. 26.4%, P = 0.25). Kaplan-Meier
      estimated graft survival at 1, 3 and 5 years were 91%, 85% and 82% in AA group,
      and 94%, 79% and 71% in NAA group (P = 0.08). The death-censored graft survival
      at 1, 3, and 5 years were 93%, 86% and 84% in AA group, and 96%, 83% and 78% in
      NAA group (P = 0.11). The 1, 3, and 5 years patient survivals were 93%, 88% and
      85% in AA group, and 96%, 96% and 94% in NAA group (P = 0.17). Highly sensitized
      AA patients could be transplanted with DD kidneys at a similar rate as NAA
      patients, and they may not have a higher incidence of rejection or an inferior
      graft survival than NAA patients.

PMID- 21091554
TI  - Metabolic imprinting by maternal protein malnourishment impairs vagal activity in
      adult rats.
AB  - Protein restriction during lactation has been suggested to diminish
      parasympathetic activity, whereas sympathetic activity is enhanced in adult rats.
      The present study analyses whether dysfunction of the autonomic nervous system is
      involved in the impairment of insulin secretion from perinatally undernourished
      rats. Male neonates were reared by mothers fed a low- (4%) protein (LP group) or
      normal- (23%) protein diet (NP group). At 81 days of age, LP rats showed less
      body mass than NP rats (318 +/- 4 g versus 370 +/- 5 g) (P < 0.001). Fat tissue
      accumulation decreased in LP [0.8 +/- 0.03 g/100 g body weight (BW)] compared to
      NP rats (1.1 +/- 0.04 g/100 g BW) (P < 0.001). LP were glucose-intolerant as
      registered by the area under the curve of an i.v. glucose tolerance test (37 +/-
      3) compared to NP rats (29 +/- 2) (P < 0.05); however, LP animals showed fasting
      normoglycaemia (LP, 5.0 +/- 0.1; NP, 4.9 +/- 0.03 mm) and hypoinsulinaemia (LP,
      0.10 +/- 0.02 ng/ml; NP, 0.17 +/- 0.02 ng/ml). LP also showed glucose tissue
      uptake 60% higher than NP rats (P < 0.05). Vagus firing rate from LP was lower
      (7.1 +/- 0.8 spikes/5 s) than that in NP rats (12.3 +/- 0.7 spikes/5 s) (P <
      0.001); however, there was no difference in sympathetic nervous activity. The
      cholinergic insulinotrophic effect was lower in pancreatic islets from LP (0.07
      +/- 0.01 ng/min/islet) than in NP rats (0.3 +/- 0.06 ng/min/islet), whereas the
      levels of adrenaline-mediated inhibition of glucose-induced insulin release were
      similar. Perinatal protein restriction inhibited the activity of the vagus nerve,
      thus reducing the insulinotrophic effect of parasympathetic pathways on
      pancreatic beta-cells, which inhibit insulin secretion.

PMID- 21091555
TI  - Epitheliotropic T-cell lymphoma in a guinea pig.
AB  - A 4-year-old female guinea pig was presented with pruritic, erythematous,
      hypotrichotic and scaling skin lesions, mainly involving the abdomen and the
      hindlegs. Clinical abnormalities were limited to the skin, and the guinea pig was
      otherwise healthy. The dermatological diagnostic work-up excluded ectoparasites,
      dermatophytosis and an endocrinopathy as differential diagnoses for the pruritus
      and hair loss. An allergic dermatitis was under investigation when the general
      and skin condition deteriorated. A neoplastic skin disorder was suspected, and
      skin biopsies revealed changes consistent with a cutaneous epitheliotropic T-cell
      lymphoma. Pautrier's microabscesses and immunophenotyped CD3(+) CD79(-)
      lymphocytes were identified. Owing to the deteriorating condition of the animal
      and the unknown but most likely poor prognosis of this disease, the guinea pig
      was euthanized. To the authors' knowledge, this is the first case report of
      cutaneous epitheliotropic T-cell lymphoma in the guinea pig with characteristic
      histopathological and immunohistochemical features.

PMID- 21091556
TI  - Sex-biased dispersal and natal philopatry in the diamondback terrapin, Malaclemys
      terrapin.
AB  - Nesting ecology and population studies indicate that diamondback terrapins
      (Malaclemys terrapin) exhibit nest site fidelity and high habitat fidelity.
      However, genetic studies indicate high levels of gene flow. Because dispersal
      affects the genetics and population dynamics of a species, we used six highly
      polymorphic microsatellite markers to investigate sex-biased dispersal and natal
      philopatry of M. terrapin in Barnegat Bay, NJ. We compared results of spatial
      autocorrelation analysis, assignment methods and Wright's F(ST) estimators to a
      mark-recapture analysis. Mark-recapture analysis over a 4-year period indicated
      that most individuals have relatively small home ranges (<2 km), with mature
      females displaying greater home ranges than males. Goodness of fit analysis of
      our mark-recapture study indicated that some juvenile males were likely transient
      individuals moving through our study location. Mean assignment indices and first
      generation migrant tests indicated that mature males were more prone to disperse
      than mature females, but first-generation migrant tests indicated that per capita
      there are more female than male dispersers. Thus, the relative importance of
      males and females on gene flow in terrapin populations may change in relation to
      population sex ratios. Spatial autocorrelation analysis indicated that mature
      females exhibited natal philopatry to nesting beaches, but first-generation
      migrant tests indicated that a small number of females failed to nest on natal
      beaches. Finally, we discuss the important conservation implications of male
      biased dispersal and natal philopatry in the diamondback terrapin.

PMID- 21091557
TI  - Contrasting mechanisms of proteomic nitrogen thrift in Prochlorococcus.
AB  - Organisms limited by carbon, nitrogen or sulphur can reduce protein production
      costs by transitions to less costly amino acids, or by reducing protein
      expression. These alternative mechanisms of nutrient thrift might respond
      differently to selection, but this possibility remains untested. We hypothesized
      that relatively invariant sequence composition responds to long-term variation in
      nutrient concentrations, whereas dynamic expression profiles vary with nutrient
      predictability. Prolonged nutrient scarcity favours proteome-wide nutrient
      reduction. Under stable, nonfluctuating nutrient availability, reduction of
      nutrient content typically occurs in proteins upregulated when nutrient
      availability is low, e.g. assimilation and catabolism. We suggest that
      fluctuating nutrient availability favours mechanisms involving short-term
      downregulation of nutrient-rich proteins. We analysed protein nitrogen content in
      six high-light, low-nutrient adapted (HL) vs. six low-light, high-nutrient
      adapted (LL) Prochlorococcus (marine cyanobacteria) strains, alongside expression
      data under experimental nitrogen and phosphorus limitation in two strains, MED4
      (HL) vs. MIT9313 (LL). HL strains contained less nitrogen, but DNA GC content
      confounded this relationship. While anabolic and catabolic proteins had normal
      nitrogen content, most strains showed reduced nitrogen in typical nitrogen stress
      response proteins. In the experimental data set, though, proteins upregulated
      under nitrogen limitation were nitrogen-poor only in MIT9313, not MED4. MIT9313
      responded similarly to nitrogen and phosphorus limitation, with slow, sustained
      downregulation of nitrogen-rich ribosomal proteins. In contrast, under nitrogen
      but not phosphorus limitation, MED4 rapidly downregulated ribosomal proteins.
      MED4's specific, rapid nitrogen response suggests adaptation to fluctuating
      conditions, supporting previous work. Thus, we identify contrasting proteomic
      nitrogen thrift mechanisms within Prochlorococcus consistent with different
      nutrient regimes.

PMID- 21091558
TI  - CpDNA-based species identification and phylogeography: application to African
      tropical tree species.
AB  - Despite the importance of the African tropical rainforests as a hotspot of
      biodiversity, their history and the processes that have structured their
      biodiversity are understood poorly. With respect to past demographic processes,
      new insights can be gained through characterizing the distribution of genetic
      diversity. However, few studies of this type have been conducted in Central
      Africa, where the identification of species in the field can be difficult. We
      examine here the distribution of chloroplast DNA (cpDNA) diversity in Lower
      Guinea in two tree species that are difficult to distinguish, Erythrophleum
      ivorense and Erythrophleum suaveolens (Fabaceae). By using a blind-sampling
      approach and comparing molecular and morphological markers, we first identified
      retrospectively all sampled individuals and determined the limits of the
      distribution of each species. We then performed a phylogeographic study using the
      same genetic data set. The two species displayed essentially parapatric
      distributions that were correlated well with the rainfall gradient, which
      indicated different ecological requirements. In addition, a phylogeographic
      structure was found for E. suaveolens and, for both species, substantially higher
      levels of diversity and allelic endemism were observed in the south (Gabon) than
      in the north (Cameroon) of the Lower Guinea region. This finding indicated
      different histories of population demographics for the two species, which might
      reflect different responses to Quaternary climate changes. We suggest that a
      recent period of forest perturbation, which might have been caused by humans,
      favoured the spread of these two species and that their poor recruitment at
      present results from natural succession in their forest formations.

PMID- 21091559
TI  - Insights into the biogeographical history of the Lower Guinea Forest Domain:
      evidence for the role of refugia in the intraspecific differentiation of Aucoumea
      klaineana.
AB  - Determining the biogeographical histories of rainforests is central to our
      understanding of the present distribution of tropical biodiversity. Ice age
      fragmentation of central African rainforests strongly influenced species
      distributions. Elevated areas characterized by higher species richness and
      endemism have been postulated to be Pleistocene forest refugia. However, it is
      often difficult to separate the effects of history and of present-day ecological
      conditions on diversity patterns at the interspecific level. Intraspecific
      genetic variation could yield new insights into history, because refugia
      hypotheses predict patterns not expected on the basis of contemporary
      environmental dynamics. Here, we test geographically explicit hypotheses of
      vicariance associated with the presence of putative refugia and provide clues
      about their location. We intensively sampled populations of Aucoumea klaineana, a
      forest tree sensitive to forest fragmentation, throughout its geographical range.
      Characterizing variation at 10 nuclear microsatellite loci, we were able to
      obtain phylogeographic data of unprecedented detail for this region. Using
      Bayesian clustering approaches, we demonstrated the presence of four
      differentiated genetic units. Their distribution matched that of forest refugia
      postulated from patterns of species richness and endemism. Our data also show
      differences in diversity dynamics at leading and trailing edges of the species'
      shifting distribution. Our results confirm predictions based on refugia
      hypotheses and cannot be explained on the basis of present-day ecological
      conditions.

PMID- 21091560
TI  - Fire increases variance in genetic characteristics of Florida Sand Skink
      (Plestiodon reynoldsi) local populations.
AB  - Fire is a complex event that maintains many ecological systems. The Florida Sand
      Skink (Plestiodon reynoldsi) is precinctive to Florida Scrub, a habitat that is
      maintained by infrequent fire. We characterize the effect of fire on genetic
      diversity and genetic differentiation at eight microsatellite loci in the Florida
      Sand Skink (n=470) collected from 30 replicate sites over three 'time since last
      fire' categories at the Archbold Biological Station. Long unburned sites had
      greater allelic richness and expected heterozygosity than either recently or
      intermediately burned sites. More recently, burned sites had greater standard
      deviations of allelic richness and private allelic richness. Expected
      heterozygosity positively correlated with 'time since fire' (r=0.36, P=0.05) and
      abundance (r=0.53, P=0.002). There was a significant spatial component to genetic
      differentiation, and results indicate individuals rarely disperse >1 km. Genetic
      differentiation was positively correlated with geographic distance in long
      unburned units (r=0.59, P=0.04), yet this relationship was disrupted by fire in
      recently (r=0.00, 1) and intermediately (r= -0.81, 0.05) burned areas.
      Simulations indicate that demographic changes to a local population could have
      generated the observed differences among 'time since fire' categories. Our
      findings indicate that infrequent fire may be beneficial to the Florida Sand
      Skink and that local populations begin to recover from changes attributable to
      the fire after 10 years. Too frequent fires may reduce genetic diversity because
      it may take multiple generations for local populations to recover.

PMID- 21091561
TI  - Intraspecific cone opsin expression variation in the cichlids of Lake Malawi.
AB  - The expression of cone opsin genes is a primary determinant of the
      characteristics of colour vision. Interspecific variation in opsin expression is
      common in African cichlids. It is correlated with foraging among cichlids from
      Lake Malawi, and with ambient light environment among cichlids from Lake
      Victoria. In this study, we tested whether gene expression varied within species
      such that it might be important in contributing to divergence. We hypothesized
      that light attenuation with depth would be correlated with predictable changes in
      gene expression in Lake Malawi, and that this variation would tune visual
      sensitivities to match the ambient light environment. We observed significant
      differences in cone opsin expression in three different comparisons among
      populations of the same species. Higher LWS expression was found in shallow
      versus deep Copadichromis eucinostomus. In Metriaclima zebra, individuals from
      Zimbawe Rock expressed significantly more SWS2B than those from Thumbi West
      Island, although these locales have similar ambient light environments. Finally,
      Tropheops gracilior from deeper water had significantly more variation in
      expression than their shallow counterparts. These results support that gene
      expression varies significantly between populations of the same species.
      Surprisingly, these results could not be explained by predicted visual
      performance as models predicted that differential expression patterns did not
      confer sensitivity advantages at different depths. This suggested that expression
      variation did not confer a local sensitivity advantage. Therefore, our findings
      were contrary to a primary requirement of the sensory bias hypothesis. As such,
      other explanations for intraspecific gene expression variation need to be tested.

PMID- 21091562
TI  - Multiple approaches to detect outliers in a genome scan for selection in
      ocellated lizards (Lacerta lepida) along an environmental gradient.
AB  - Identification of loci with adaptive importance is a key step to understand the
      speciation process in natural populations, because those loci are responsible for
      phenotypic variation that affects fitness in different environments. We conducted
      an AFLP genome scan in populations of ocellated lizards (Lacerta lepida) to
      search for candidate loci influenced by selection along an environmental gradient
      in the Iberian Peninsula. This gradient is strongly influenced by climatic
      variables, and two subspecies can be recognized at the opposite extremes: L.
      lepida iberica in the northwest and L. lepida nevadensis in the southeast. Both
      subspecies show substantial morphological differences that may be involved in
      their local adaptation to the climatic extremes. To investigate how the use of a
      particular outlier detection method can influence the results, a frequentist
      method, DFDIST, and a Bayesian method, BayeScan, were used to search for outliers
      influenced by selection. Additionally, the spatial analysis method was used to
      test for associations of AFLP marker band frequencies with 54 climatic variables
      by logistic regression. Results obtained with each method highlight differences
      in their sensitivity. DFDIST and BayeScan detected a similar proportion of
      outliers (3-4%), but only a few loci were simultaneously detected by both
      methods. Several loci detected as outliers were also associated with temperature,
      insolation or precipitation according to spatial analysis method. These results
      are in accordance with reported data in the literature about morphological and
      life-history variation of L. lepida subspecies along the environmental gradient.

PMID- 21091563
TI  - Species delimitation of common reef corals in the genus Pocillopora using
      nucleotide sequence phylogenies, population genetics and symbiosis ecology.
AB  - Stony corals in the genus Pocillopora are among the most common and widely
      distributed of Indo-Pacific corals and, as such, are often the subject of
      physiological and ecological research. In the far Tropical Eastern Pacific (TEP),
      they are major constituents of shallow coral communities, exhibiting considerable
      variability in colony shape and branch morphology and marked differences in
      response to thermal stress. Numerous intermediates occur between morphospecies
      that may relate to extensive hybridization. The diversity of the Pocillopora
      genus in the TEP was analysed genetically using nuclear ribosomal (ITS2) and
      mitochondrial (ORF) sequences, and population genetic markers (seven
      microsatellite loci). The resident dinoflagellate endosymbiont (Symbiodinium sp.)
      in each sample was also characterized using sequences of the internal transcribed
      spacer 2 (ITS2) rDNA and the noncoding region of the chloroplast psbA minicircle.
      From these analyses, three symbiotically distinct, reproductively isolated,
      nonhybridizing, evolutionarily divergent animal lineages were identified.
      Designated types 1, 2 and 3, these groupings were incongruent with traditional
      morphospecies classification. Type 1 was abundant and widespread throughout the
      TEP; type 2 was restricted to the Clipperton Atoll; and type 3 was found only in
      Panama and the Galapagos Islands. Each type harboured a different
      Symbiodinium'species lineage' in Clade C, and only type 1 associated with the
      'stress-tolerant'Symbiodinium glynni (D1). The accurate delineation of species
      and implementation of a proper taxonomy may profoundly improve our assessment of
      Pocillopora's reproductive biology, biogeographic distributions, and resilience
      to climate warming, information that must be considered when planning for the
      conservation of reef corals.

PMID- 21091564
TI  - Night and day: the comparative study of strepsirrhine primates reveals
      socioecological and phylogenetic patterns in olfactory signals.
AB  - Studies of chemical signals in vertebrates typically target single species;
      however, a broader understanding of olfactory communication may derive from
      comparative studies. We collected urine from 12 species representing most
      families of strepsirrhine primates--an excellent model clade because of variation
      in scent marking and socioecology. Using SPDE/GC-MS, we identified the volatile
      chemical composition of male and female urine from six 'urine marking' species
      and six glandular or 'non-urine marking' species. We found no sex differences,
      but as predicted, urine markers expressed the most chemically complex and
      distinctive urine. More distantly related species had more dissimilar urinary
      profiles, suggesting gradual signal evolution. Reconstructing ancestral chemical
      profiles revealed different evolutionary trajectories for urine and non-urine
      markers. We suggest that urine marking is an ancestral behaviour related to
      solitary, nocturnal living and that parallel evolutionary shifts towards greater
      reliance on derived glandular marking occurred in a family (Lemuridae)
      characterized by diurnality and sociality.

PMID- 21091565
TI  - Genetic divergence in morphology-performance mapping between Misty Lake and inlet
      stickleback.
AB  - Different environments should select for different aspects of organismal
      performance, which should lead to correlated divergence in morphological traits
      that influence performance. The result should be genetic divergence in aspects of
      performance, morphology and associations ('maps') between morphology and
      performance. Testing this hypothesis requires quantifying performance and
      morphology in multiple populations after controlling for environmental
      differences, but this is rarely attempted. We used a common-garden experiment to
      examine morphology and several aspects of swimming performance within and between
      the lake and inlet populations of threespine stickleback (Gasterosteus aculeatus)
      from the Misty system, Vancouver Island, Canada. Controlling for body size, lake
      stickleback had shallower bodies, larger caudal fins and smaller pelvic girdles.
      With or without morphological covariates, lake stickleback showed greater
      performance in both sustained and burst swimming. In contrast, inlet stickleback
      showed greater manoeuverability than did lake stickleback in some analyses.
      Morphology-performance relationships were decoupled when considering variation
      within vs. between populations. Moreover, morphology-performance mapping differed
      between the two populations. Based on these observations, we advance a hypothesis
      for why populations adapting to different environments should show adaptive
      genetic divergence in morphology-performance mapping.

PMID- 21091566
TI  - Parasite-mediated evolution of the functional part of the MHC in primates.
AB  - The major histocompatibility complex (MHC) is a key model of genetic
      polymorphism, but the mechanisms underlying its extreme variability are debated.
      Most hypotheses for MHC diversity focus on pathogen-driven selection and predict
      that MHC polymorphism evolves under the pressure of a diverse parasite fauna.
      Several studies reported that certain alleles offer protection against certain
      parasites, yet it remains unclear whether variation in parasite pressure more
      generally covaries with allelic diversity and rates of molecular evolution of MHC
      across species. We tested this prediction in a comparative study of 41 primate
      species. We characterized polymorphism of the exon 2 of DRB region of the MHC
      class II. Our phylogenetic analyses controlled for the potential effects of
      neutral mutation rate, population size, geographic origin and body mass and
      revealed that nematode species richness associates positively with nonsynonymous
      nucleotide substitution rate at the functional part of the molecule. We failed to
      find evidence for allelic diversity being strongly related to parasite species
      richness. Continental distribution was a strong predictor of both allelic
      diversity and substitution rate, with higher values in Malagasy and Neotropical
      primates. These results indicate that parasite pressure can influence the
      different estimates of MHC polymorphism, whereas geography plays an independent
      role in the natural history of MHC.

PMID- 21091567
TI  - The consequences of phenotypic plasticity for ecological speciation.
AB  - We use an individual-based numerical simulation to study the effects of
      phenotypic plasticity on ecological speciation. We find that adaptive plasticity
      evolves readily in the presence of dispersal between populations from different
      ecological environments. This plasticity promotes the colonization of new
      environments but reduces genetic divergence between them. We also find that the
      evolution of plasticity can either enhance or degrade the potential for divergent
      selection to form reproductive barriers. Of particular importance here is the
      timing of plasticity in relation to the timing of dispersal. If plasticity is
      expressed after dispersal, reproductive barriers are generally weaker because
      plasticity allows migrants to be better suited for their new environment. If
      plasticity is expressed before dispersal, reproductive barriers are either
      unaffected or enhanced. Among the potential reproductive barriers we considered,
      natural selection against migrants was the most important, primarily because it
      was the earliest-acting barrier. Accordingly, plasticity had a much greater
      effect on natural selection against migrants than on sexual selection against
      migrants or on natural and sexual selection against hybrids. In general,
      phenotypic plasticity can strongly alter the process of ecological speciation and
      should be considered when studying the evolution of reproductive barriers.

PMID- 21091568
TI  - Male attractiveness, fertility and susceptibility to oxidative stress are
      influenced by inbreeding in Drosophila simulans.
AB  - Inbreeding frequently leads to inbreeding depression, a reduction in the trait
      values of inbred individuals. Inbreeding depression has been documented in
      sexually selected characters in several taxa, and while there is correlational
      evidence that male fertility is especially susceptible to inbreeding depression,
      there have been few direct experimental examinations of this. Here, we assessed
      inbreeding depression in male fertility and a range of other male fitness
      correlates in Drosophila simulans. We found that male fertility and
      attractiveness were especially susceptible to inbreeding depression.
      Additionally, levels of testicular oxidative stress were significantly elevated
      in inbred males, although sperm viability did not differ between inbred and
      outbred males. Copulation duration, induction of oviposition, and the proportion
      of eggs hatching did not differ for females mated to inbred or outbred males.
      Nevertheless, our results clearly show that key male fitness components are
      impaired by inbreeding and provide evidence that aspects of male fertility are
      especially susceptible to inbreeding depression.

PMID- 21091569
TI  - An experimental test for alternative reproductive strategies underlying a female
      limited polymorphism.
AB  - Polymorphism often corresponds to alternative mating tactics in males, but much
      less is known about this relationship in females. However, recent work suggests
      that selection for alternative reproductive strategies in females can maintain
      genetic variation in important life-history traits. Brown anole lizards (Anolis
      sagrei) exhibit a genetically based polymorphism in dorsal pattern that is
      expressed only by females, which occur in bar (B), diamond (D) and intermediate
      diamond-bar (DB) morphs. Here, we use a combination of natural history data,
      captive breeding studies and phenotypic manipulations of reproductive investment
      to test the hypothesis that this polymorphism corresponds to morph-specific
      patterns of reproductive investment. Three years of data from wild females and
      two generations of captive breeding revealed no differences among morphs in the
      frequency of egg production or in the number, frequency, size or sex ratio of
      offspring. Manipulations of reproductive investment via surgical ovariectomy
      revealed significant costs of reproduction with respect to survival, growth,
      immune function and haematocrit, but the magnitudes of these costs did not differ
      among morphs. Collectively, our results refute the hypothesis that this sex
      limited polymorphism is maintained by selection for alternative reproductive
      strategies. We compare this finding to other systems in which polymorphic females
      exhibit alternative reproductive tactics and discuss other selective factors that
      could maintain polymorphism in anoles.

PMID- 21091570
TI  - Strain filtering and transmission of a mixed infection in a social insect.
AB  - Mixed-genotype infections have attracted considerable attention as drivers of
      pathogen evolution. However, experimental approaches often overlook essential
      features of natural host-parasite interactions, such as host heterogeneity, or
      the effects of between-host selection during transmission. Here, following
      inoculation of a mixed infection, we analyse the success of different strains of
      a trypanosome parasite throughout the colony cycle of its bumblebee host. We find
      that most colonies efficiently filter the circulating infection before it reaches
      the new queens, the only offspring that carry infections to the next season. A
      few colonies with a poor filtering ability thus contributed disproportionately to
      the parasite population in the next season. High strain diversity but not high
      infection intensity within colony was associated with an increased probability of
      transmission of the infection to new queens. Interestingly, the representation of
      the different strains changed dramatically over time, so that long-term parasite
      success could not be predicted from short-term observations. These findings
      highlight the shaping of within-colony parasite diversity through filtering as a
      crucial determinant of year-to-year pathogen transmission and emphasize the
      importance of host ecology and heterogeneity for disease dynamics.

PMID- 21091571
TI  - Limited gene flow may enhance adaptation to local optima in isolated populations
      of the Roesel's bush cricket (Metrioptera roeselii).
AB  - Variation in morphological traits along latitudinal gradients often manifests as
      size clines. In insects, both positive and negative correlations are seen, and
      the mechanism behind the response is unclear. We studied variation in seven
      morphological traits of Roesel's bush cricket, Metrioptera roeselii, sampled from
      seven latitude-matched-pair populations that were either geographically isolated
      from or connected to the species continuous distribution range. The aim was to
      examine whether morphological traits differed between isolated and continuous
      populations, and whether latitudinal variation was apparent. The data were used
      to indicate whether variation in trait means originates from plastic responses to
      the environment or genetic adaptation to local conditions. To evaluate the
      influence of gene flow on trait means, we analysed the genetic variation in seven
      microsatellites. Data showed that individuals from isolated populations display a
      positive relationship between latitude and body size, whereas individuals from
      continuous populations show little or no such relationship. The combined
      morphological and genetic data suggest that the isolated populations have adapted
      to local optima, while gene flow between continuous populations appears to
      counteract this process.

PMID- 21091572
TI  - Testing the molecular and evolutionary causes of a 'leapfrog' pattern of
      geographical variation in coloration.
AB  - Understanding the mechanisms accounting for the evolution of phenotypic diversity
      is central to evolutionary biology. We use molecular and phenotypic data to test
      hypotheses for 'leapfrog' patterns of geographical variation, in which
      phenotypically similar, disjunct populations are separated by distinct
      populations of the same species. Phylogenetic reconstructions revealed
      independent evolution of melanic plumage characters in different populations in
      the Neotropical avian genus Arremon. Thus, phenotypic similarities between
      distant populations cannot be explained by close phylogenetic affinity. Nor can
      they be attributed to recurring mutations in the MC1R gene, a locus involved in
      melanic pigmentation. A coalescent analysis indicates that plumage traits have
      become fixed at a faster rate than expected under genetic drift, suggesting that
      selection underlies their repeated evolution. In contrast to views that genetic
      drift drives phenotypic differentiation in Neotropical montane birds, our results
      imply that geographical variation preceding speciation may reflect the action of
      deterministic selective processes.

PMID- 21091573
TI  - A geographic mosaic of trophic interactions and selection: trees, aphids and
      birds.
AB  - Genetic variation in plants is known to influence arthropod assemblages and
      species interactions. However, these influences may be contingent upon local
      environmental conditions. Here, we examine how plant genotype-based trophic
      interactions and patterns of natural selection change across environments.
      Studying the cottonwood tree, Populus angustifolia, the galling aphid, Pemphigus
      betae and its avian predators, we used three common gardens across an
      environmental gradient to examine the effects of plant genotype on gall
      abundance, gall size, aphid fecundity and predation rate on galls. Three patterns
      emerged: (i) plant genotype explained variation in gall abundance and predation,
      (ii) G*E explained variation in aphid fecundity, and environment explained
      variation in gall abundance and gall size, (iii) natural selection on gall size
      changed from directional to stabilizing across environments.

PMID- 21091574
TI  - Inbreeding depression in the competitive fertilization success of male crickets.
AB  - Mating between close relatives generally results in offspring of decreased
      fitness. Inbreeding depression is generally greater for life-history traits than
      for morphological traits, and recent studies of traits subject to sexual
      selection suggest that these may suffer the greatest inbreeding depression.
      Sexual selection continues after mating in the form of sperm competition and
      cryptic female choice, imposing strong selection on male competitive
      fertilization success. Here, I examine the effects of a single generation of full
      sib mating on competitive fertilization success in a cricket, Teleogryllus
      oceanicus. The estimated coefficient of inbreeding depression in competitive
      fertilization success was 0.37, higher than that for other life-history and
      morphological traits. Such intense inbreeding depression coupled with little or
      no additive genetic variance for this trait is consistent with strong directional
      selection on male competitive fertilization success generating high levels of
      dominance variance, and provides an adaptive explanation for the evolution of
      inbreeding avoidance found in this species.

PMID- 21091575
TI  - Altitudinal and seasonal variation in microsatellite allele frequencies of
      Drosophila buzzatii.
AB  - Variation in climate, particularly temperature, is known to affect the genetic
      composition of populations. Although there have been many studies of latitudinal
      variation, comparisons of populations across altitudes or seasons, particularly
      for animal species, are less common. Here, we study genetic variation
      (microsatellite markers) in populations of Drosophila buzzatii collected along
      altitudinal gradients and in different seasons. We found no differences in
      genetic variation between 2 years or between seasons within years. However, there
      were numerous cases of significant associations between allele frequencies or
      expected heterozygosities and altitude, with more than half showing nonlinear
      relationships. While these associations indicate possible selection and local
      altitudinal adaptation, direct tests gave strong evidence for selection affecting
      two loci and weaker evidence for five other loci. Two loci that are located
      within an inversion (including the one with strongest evidence for selection)
      show a linear increase in genetic diversity with altitude, likely due to thermal
      selection. Parallel associations with altitude here and with latitude in
      Australian populations indicate that selection is operating on chromosomal
      regions marked by some of the loci.

PMID- 21091576
TI  - Loss of the protein-tyrosine phosphatase DEP-1/PTPRJ drives meningioma cell
      motility.
AB  - DEP-1/PTPRJ is a transmembrane protein-tyrosine phosphatase which has been
      proposed as a suppressor of epithelial tumors. We have found loss of
      heterozygosity (LOH) of the PTPRJ gene and loss of DEP-1 protein expression in a
      subset of human meningiomas. RNAi-mediated suppression of DEP-1 in DEP-1 positive
      meningioma cell lines caused enhanced motility and colony formation in semi-solid
      media. Cells devoid of DEP-1 exhibited enhanced signaling of endogenous platelet
      derived growth factor (PDGF) receptors, and reduced paxillin phosphorylation upon
      seeding. Moreover, DEP-1 loss caused diminished adhesion to different matrices,
      and impaired cell spreading. DEP-1-deficient meningioma cells exhibited invasive
      growth in an orthotopic xenotransplantation model in nude mice, indicating that
      elevated motility translates into a biological phenotype in vivo. We propose that
      negative regulation of PDGF receptor signaling and positive regulation of
      adhesion signaling by DEP-1 cooperate in inhibition of meningioma cell motility,
      and possibly tumor invasiveness. These phenotypes of DEP-1 loss reveal functions
      of DEP-1 in adherent cells, and may be more generally relevant for tumorigenesis.

PMID- 21091577
TI  - Symptoms and signs differentiating croup and epiglottitis.
AB  - AIM: To determine differentiating symptoms and signs of epiglottitis and
      laryngotracheobronchitis (croup). METHODS: Contemporaneous interview of parents
      and clinical examination of children with acute upper airway obstruction
      presenting to the intensive care unit of a paediatric hospital. RESULTS: Two
      hundred and three children were examined over a 40-month period. One hundred and
      two had croup, of whom 49 had the diagnosis confirmed at intubation and another
      six by direct laryngeal inspection without intubation. One hundred and one had
      epiglottitis of whom 95 were diagnosed by direct inspection of the larynx at
      intubation, five by a lateral X-ray of the neck and one on direct inspection
      without intubation. One child with epiglottitis died. Although both illnesses
      presented with stridor, the additional presence of drooling had a high
      sensitivity (0.79, 95% CI 0.70-0.86) and specificity (0.94, 95% CI 0.88-0.97) for
      epiglottitis while coughing had a high sensitivity (1.00, 95% CI 0.96-1.00) and
      high specificity (0.98, 95% CI 0.93-0.99) for croup. Coughing predicted croup but
      drooling predicted epiglottitis. Additional reliable signs of epiglottitis were a
      preference to sit, refusal to swallow and dysphagia. Thirty-seven percent of
      children with epiglottitis and 16% with croup were treated as having another
      respiratory illness at least once before definitive diagnosis. CONCLUSIONS:
      Epiglottitis and croup are often confused because they share symptoms and signs
      including stridor. However, differentiation in early illness is possible by
      additional observation of coughing and absence of drooling in croup and by the
      additional observation of drooling with absence of coughing in epiglottitis.

PMID- 21091578
TI  - Neonatal resuscitation capacity in Nepal.
AB  - AIM: Perinatal asphyxia is a major contributor to the nearly 4 million neonatal
      deaths worldwide each year in resource-limited settings. Neonatal resuscitation,
      a proven method for preventing newborn deaths, is effective only when local
      caregivers have proper training and access to essential supplies. There are few
      published data describing neonatal resuscitation capacity in Nepal, where
      neonatal mortality rates are high. The goal of this study was to quantify
      neonatal resuscitation capacity at birthing sites in urban and rural Nepal.
      METHODS: Seventeen birth centres ranging from tertiary care hospitals to rural
      health posts were evaluated. Assessments included standardised interviews of
      health-care workers and evaluation of newborn resuscitation areas. The
      availability of essential resuscitation tools was recorded. RESULTS: Eleven of
      the 17 health centres conducted deliveries on-site. Of those, 45% had posted and
      visible resuscitation algorithms; 72% had infant warmers; 91% had mechanical
      suction machines; 36% had bulb suctions and 82% had bag-mask ventilation devices
      available. Tertiary hospitals were much better equipped compared with smaller
      health centres. None of the health-care workers who attended home deliveries had
      access to algorithms, warming devices, suction or bag-mask ventilation devices.
      CONCLUSIONS: Availability of appropriate resuscitation supplies was variable in
      health centres providing delivery services on-site and was severely deficient
      among health staff attending to home deliveries. Limited availability of
      resuscitation equipment may contribute to the high neonatal mortality rates seen
      in Nepal. Sustainable training programmes and distribution of neonatal
      resuscitation equipment are critical priorities in this region.

PMID- 21091579
TI  - Correlation between developmental quotients (DASII) and social quotient (Malin's
      VSMS) in Indian children aged 6 months to 2 years.
AB  - AIM: To determine correlation between developmental quotients (DQ) (DASII) and
      social quotients (SQ) (Malin's Vineland Social Maturity Scale (VSMS)). METHODS:
      Malin's VSMS and DASII were done in 135 children aged 6 months to 2 years. SQ and
      DQ motor and mental were correlated using Pearson's correlation coefficient (r).
      Mean SQ and DQ and age equivalent scores were compared. RESULTS: Correlation
      coefficients between SQ and DQ (mental and motor were 0.849 and 0.791,
      respectively. Social age correlated highly with mental age (r = 0.906). Mean SQ
      was higher than mean DQa. CONCLUSION: SQ tends to be higher than DQ and
      correlates best with DQ mental.

PMID- 21091580
TI  - Closing the evidence-practice gap for newborn pain using clinical networks.
AB  - AIM: The Australian New Zealand Neonatal Network undertook a project to close the
      evidence practice gap for the management of newborn pain in neonatal units within
      Australia. The aim was to establish a process for using evidence to support
      practice change and in doing so close the existing practice evidence gap for
      newborn pain. METHOD: An implementation model using a clinical network with state
      facilitators, local champions and project teams was used in 24 tertiary units and
      six district hospitals throughout Australia. The process included audit and
      feedback, benchmarking, educational workshops on critical appraisal and audit of
      family awareness of pain. Multiple types of data were collected to enable changes
      in practices for pain management to be evaluated. RESULTS: There was a 21%
      overall improvement in the number of infants receiving breastfeeding or sucrose
      for procedural pain, however, breastfeeding rates remain poorly utilised. The use
      of a pain assessment tool increased from 14% to 22%, with 56% of units
      introducing the use of an assessment tool into their practice. Families became
      more aware that their infant can experience pain and strategies to manage the
      pain (from 19% to 57%) project through distribution of information. CONCLUSION:
      The networks for the uptake of evidence program have enabled the topic of
      procedure pain in neonates to be evaluated. We have shown that through a well
      planned program of coordination, facilitation and using local champions and
      project teams a change in practice can occur.

PMID- 21091581
TI  - The Australian cerebral palsy research study--protocol for a national
      collaborative study investigating genomic and clinical associations with cerebral
      palsy.
AB  - AIM: Previous studies have proposed a link between the presence of specific
      single nucleotide polymorphisms (SNPs) and cerebral palsy and the majority of
      these associations remain to be confirmed or rejected by prospective studies with
      sufficient statistical power. Prior studies have also given little attention to
      the interaction of genomic characteristics and clinical risk factors. METHODS:
      This paper describes the design of a prospective case-control study to test these
      genetic associations in conjunction with more stringent data collection in
      respect to clinical features associated with pregnancy, particularly maternal
      infection. Here we consider the ethical requirements, our hypothesis that genetic
      susceptibility modifies the risk of cerebral palsy in the presence of perinatal
      environmental triggers, a priori primary and secondary aims, power calculations,
      participant recruitment strategies, data linkage, sampling methods of genetic
      material and subsequent SNP analysis, collection of clinical data and the
      proposed final statistical analysis.

PMID- 21091582
TI  - Post-natal growth of 157 children born as extremely premature neonates.
AB  - AIM: With increasing survival rate of extremely premature neonates, their long
      term outcomes including growth and risk factors for later disorders need to be
      considered. We prospectively evaluated anthropometric parameters in children born
      as extremely premature neonates. METHODS: Anthropometric parameters were measured
      at the ages of 2 and 5 years in 72 extremely premature children born between the
      22nd and 25 + 6th weeks of gestation (group I) and 85 children born between the
      26th and 27 + 6th weeks of gestation (group II). RESULTS: Although catch-up in
      the postnatal growth was observed in both groups of children, resulting in growth
      improvement, the height of the extremely premature children at the ages of 2 and
      5 years remains lower (P < 0.01) compared with the control population. A decline
      in head growth was observed in both groups between the ages of 2 and 5 years,
      resulting in decrease of standard deviation score (SDS) for head circumference
      (HC) in comparison with that of the control population, accompanied by an
      increased number of children with microcephaly, defined as HC < -2 SD. At the age
      of five, microcephaly was found in 18% of children from group I and 11.7% of
      children from group II. At the age of 5 years, the waist and hip circumferences
      and ten skinfolds were not different between both groups of children. CONCLUSION:
      Long-term follow-up of extremely premature neonates is important not only to
      establish their growth patterns but also for risk factors assessment including
      adiposity for later development of adult-onset diseases.

PMID- 21091583
TI  - Awareness, possession and use of insecticide-treated nets for prevention of
      malaria in children under five in Abeokuta, Nigeria.
AB  - AIM: A survey was carried out to assess awareness, possession and use of
      insecticide-treated nets (ITN) by mothers in preventing malaria among children
      under 5 years old. METHODS: Pretested questionnaires were administered by trained
      research assistants to women that have had a child in the last 59 months,
      irrespective of place of child delivery. RESULTS: Malaria was considered
      dangerous by almost all respondents (98.5%); the level of awareness of ITN as a
      malaria preventive tool was 75.1% while possession was 45%. Awareness and
      possession of ITN were positively and significantly influenced by high
      educational qualification of mothers and attendance of a public hospital for
      antenatal care. Hospitals were identified as the major source of awareness among
      respondents; women that delivered their babies in traditional birth home
      displayed least awareness (38.6%) and recorded low possession (10%). There was no
      significant relationship between ITN usage, birth order and age of child. Heat
      experienced while sleeping under ITN and problem of how to hang the net were
      major limitations identified in the use of ITN. CONCLUSION: The need to involve
      women receiving antenatal care outside the hospital in malaria control
      intervention is hereby recommended. Methods of bridging ITN possession and use
      needs to de developed.

PMID- 21091584
TI  - Health of Australian children in out-of-home care: needs and carer recognition.
AB  - AIM: Following research highlighting high levels of health need in New South
      Wales children in out-of-home care, this study aimed to quantify health need in a
      sample of Queensland children in care based on multidisciplinary child health
      assessments. The study also sought to examine the concordance between foster
      carers' health concerns for children for whom they are providing care and health
      need as established through referrals made as a result of health assessment.
      METHODS: Children entering out-of-home care in the north Brisbane area within the
      previous month were referred for baseline child health assessment. Child health
      was assessed by paediatricians and clinical nurses utilising a pro forma-based
      methodology. Analysis of initial carer concerns, health referrals and
      immunisation status in the sample was undertaken. RESULTS: Of the 63 children
      assessed, 70% were found to require multiple referrals to various health
      services. The most frequently made referrals included paediatrician follow-up
      (41% of children), counselling services (30%) and audiology (26%). Only 68% of
      the sample was found to be fully immunised. A discrepancy was noted between
      foster carers' child health concerns and level of referral need established
      during assessment. CONCLUSIONS: Queensland children in care have high health
      needs similar to those evidenced by children in care in other areas of Australia.
      Foster carers appear to underestimate the health needs of children in their care,
      demonstrating the necessity of multidisciplinary health screens and foster carer
      training in order to detect child health problems in this population.

PMID- 21091585
TI  - Preterm infants with chronic lung disease: are protein and energy intakes after
      discharge sufficient for optimal growth?
AB  - AIM: To document post-discharge feeding practices of preterm infants with chronic
      lung disease (CLD) and determine if sufficient protein and energy is consumed for
      optimal growth. METHOD: Protein and energy intakes of preterm infants with CLD
      were quantified through detailed analysis of measured food and fluid intakes at
      four corrected age (CA) assessments, post-discharge. Most of the infants were in
      hospital for the term assessment. Milk intake from breastfeeding was determined
      by test weighing. Protein and energy intakes were compared with the Australian
      and New Zealand Nutrient Reference Values (NRV) for healthy term-born infants,
      and CA z-scores for weight, length and head circumference were calculated using
      Australian national gestational growth data and Centre for Disease Control 2000
      growth data. RESULTS: Ten of the 28 CLD infants who were exclusively receiving
      expressed breast milk in hospital were transitioned to infant formula within 1
      month of discharge. Complementary foods were introduced at a median CA of 3.6
      months. Protein intakes almost always exceeded the NRV for healthy term-born
      infants, and at each assessment, at least 63% of infants met the energy NRV.
      Longitudinal growth data are available for 20 infants, four of whom had been
      small for gestational age. At the 12-month assessment, 10 of these infants
      weighed less than the 10th percentile. CONCLUSION: Preterm infants who develop
      CLD do not always achieve reference growth in their first year following
      discharge, despite protein and energy intakes being mostly comparable to those
      recommended for healthy term-born infants.

PMID- 21091587
TI  - Early development of children with major birth defects requiring newborn surgery.
AB  - AIM: To describe neurodevelopmental outcomes of neonates following cardiac or non
      cardiac surgery for major birth defects. METHODS: From 1 June 2002 to 31 July
      2004, infants born >= 33 weeks gestation who underwent major birth defect surgery
      were enrolled prospectively. Infants were assessed at a mean corrected age of 24
      months (standard deviation (SD) = 8 months, range 18-36 months) using the Bayley
      Scales of Infant Development: Second Edition. RESULTS: Of the 118 study infants,
      79 (66%) were male, the mean gestation was 38.5 weeks (SD 1.9 weeks) and mean
      birthweight was 3194 g (SD 653 g). Forty-five infants (47%) had undergone general
      surgery for non-cardiac defects. The majority of infants (73%) performed below
      average in cognitive and language skills. Mental delay was found in 41% of
      infants; 16% were significantly delayed. Fine and gross motor skills were below
      average in 60% of infants. Twenty-six percent of infants had motor delay; 9% were
      significantly delayed. Both the mean Mental Development Index (M = 88, SD = 19.8)
      and mean Psychomotor Development Index (M = 93, SD = 19.3) were significantly
      below the normative mean (d = 0.8, P < 0.001 and d = 0.5, P < 0.001,
      respectively). One in five children had global developmental delay. There was no
      significant difference in outcome between the cardiac and general surgery groups.
      CONCLUSIONS: The majority of infants performed below average on a standardised
      test of infant development. Our results show that infants requiring newborn
      surgery for major birth defects are at high risk of adverse neurodevelopmental
      outcomes. We recommend that follow-up programmes include systematic
      multidisciplinary developmental monitoring and early intervention.

PMID- 21091586
TI  - Serial measurements of serum alkaline phosphatase for early prediction of
      osteopaenia in preterm infants.
AB  - AIM: Osteopaenia commonly occurs in preterm infants; however, its diagnosis is
      often delayed when based on radiological findings. The aim of this study was to
      examine whether serial measurements of bone turnover markers are useful for early
      prediction of osteopaenia in preterm infants. METHODS: Premature infants of <= 34
      weeks gestation were enrolled. Serum alkaline phosphatase (ALP), bone form ALP
      (BALP), calcium and inorganic phosphate were concurrently measured biweekly from
      3 weeks post-natal age until 40 weeks post-conceptional age. Radiographic
      examination of the forearm was performed at term age. Osteopaenia was defined as
      positive radiographic findings according to Koo's criteria. RESULTS: Of the 46
      premature infants completing the follow-up study at term age, 18 showed
      osteopaenia in radiographic examination. Serum ALP was highly correlated with
      BALP (R(2) = 0.93, P < 0.001). Infants who had osteopaenia showed a higher level
      of ALP and BALP after 3 weeks post-natal age than those who had no osteopaenia.
      ALP concentration exceeding 700 IU/L at 3 weeks post-natal age was predictive of
      osteopaenia at term age (sensitivity 73% and specificity 73%) and so did for the
      predictive value of BALP concentration exceeding 95 ug/L (sensitivity 73% and
      specificity 80%). BALP measures provided no greater benefit of diagnostic
      performance than ALP in early detection of osteopaenia. Furthermore, premature
      infants with osteopaenia showed similar levels of calcium and inorganic
      phosphatase concentration compared with those without. CONCLUSION: Serum ALP
      concentration exceeding 700 IU/L at 3 weeks post-natal age can predict the risk
      of osteopaenia in preterm infants.

PMID- 21091588
TI  - Should what we know about neurobehavioral development, complex congenital heart
      disease, and brain maturation affect the timing of corrective cardiac surgery?
AB  - Despite remarkable improvements in perioperative care, adverse neurobehavioral
      outcomes following neonatal and infant cardiac surgery are commonplace and are
      associated with substantial morbidity. It is becoming increasingly clear that
      complex congenital heart disease is associated with both abnormalities in
      neuroanatomic development and a delay in fetal brain maturation. Substantial
      cerebral ischemic/hypoxic injury has been detected in neonates with complex
      congenital heart disease both prior to and following corrective cardiac surgery.
      The brain of the neonate with complex congenital heart disease appears to be
      uniquely vulnerable to the types of ischemic/hypoxic injury associated with
      perioperative care. It remains to be determined whether delaying surgical
      correction to allow for brain maturation will be associated with improvements in
      neurobehavioral outcomes.

PMID- 21091589
TI  - Buprenorphine TTS for children--a review of the drug's clinical pharmacology.
AB  - OBJECTIVE: The transdermal therapeutic system (TTS) with buprenorphine is
      currently being used 'off-label' to treat chronic pediatric pain. We compiled
      available pharmacokinetic (PK), pharmacodynamic (PD), and clinical pediatric data
      on buprenorphine to rationalize treatment regimens. METHODS: We conducted a
      systematic biomedical literature review focusing on pediatric buprenorphine data.
      RESULTS: There are few relevant pediatric buprenorphine data, particularly in
      children suffering chronic pain. There are no pediatric PK and PD data for
      children with chronic pain given sublingual or TTS formulations. Children given
      single dose buprenorphine have increased drug clearance referenced to bodyweight
      with a possible paradoxical longer duration of action. Buprenorphine metabolism
      is independent of renal function, which is advantageous in renal insufficiency.
      The risk of respiratory depression after buprenorphine is difficult to quantify.
      A concentration-response relationship for respiratory effects has not been
      described and it is unknown whether children have a ceiling effect similar to
      that described in healthy adult volunteers. CONCLUSIONS: Buprenorphine is of
      interest in pediatric postoperative pain and cancer pain control because of its
      multiple administration routes, long duration of action, and metabolism largely
      independent of renal function. There is little reason to expect buprenorphine
      effects in children out of infancy are fundamentally different to those in
      adults. From the limited pediatric data available, it appears that buprenorphine
      has no higher adverse potential than the more commonly used opioids. There is an
      urgent need for focused PK, PD, and safety studies in children before use in
      children becomes more widespread.

PMID- 21091590
TI  - Cardiac arrest in anesthetized children: recent advances and challenges for the
      future.
AB  - Over the past 50 years the incidence of anesthesia-related cardiac arrest has
      declined, despite increased patient co-morbidities, the most significant
      determinant of anesthetic risk. Multiple factors have contributed to this
      improvement including safer anesthetic agents, better monitoring devices and the
      development of a specialized pediatric environment. Provider skill has benefitted
      from improved training and recognition of high-risk situations. Further
      improvements will depend on international, multispecialty efforts to standardize
      terminology and analyze large numbers of these infrequent adverse events.

PMID- 21091591
TI  - An approach to integrated data assessment in a proficiency test on the
      enumeration of Escherichia coli.
AB  - AIMS: To develop appropriate statistical approaches to plan and evaluate
      proficiency tests for the enumeration of Escherichia coli, addressing, in
      particular, a possible but frequently unavoidable lack of test sample
      homogeneity. METHODS AND RESULTS: Each of 50 laboratories analysed two samples of
      a stabilized suspension of E. coli in duplicate, using various media, inoculation
      methods, and incubation times and conditions. In parallel, the E. coli suspension
      was tested by the organiser for homogeneity and stability. Escherichia coli
      counts followed a log-normal distribution. After eliminating, by Youden analysis,
      two data sets that were considered outliers and eight data sets for
      underperformance of the laboratories (substantial lack of repeatability), the
      standard deviation of the mean was about 0.06 log(10) units. There was no
      evidence of bimodality of the data. Lack of homogeneity of distribution of
      bacteria had a strong effect on measurement uncertainty, in addition to
      laboratory bias and method repeatability. The homogeneity decreases during
      storage of the individual test vials; this effect could be modelled by the known
      kinetics of inactivation of micro-organisms. The results were confirmed by Monte
      Carlo simulations. CONCLUSIONS: By a tailored analysis of proficiency testing
      data, it is possible to distinguish the effect of lack of homogeneity, laboratory
      bias and method repeatability, on the measurement uncertainty. SIGNIFICANCE AND
      IMPACT OF THE STUDY: A statistic tool is provided to solve problems related to
      lack of stability of microbiological test material and to separate the effects of
      sample inhomogeneity from the performance of the individual laboratory.

PMID- 21091592
TI  - Distribution of selected virulence genes and antibiotic resistance in
      Enterococcus species isolated from the South Nation River drainage basin,
      Ontario, Canada.
AB  - AIMS: Isolate and characterize water enterococci from the South Nation River
      drainage basin, an area dominated by agriculture. METHODS AND RESULTS: A total of
      1558 enterococci were isolated from 204 water samples from the South Nation River
      obtained over a 3-year period. PCR was used to identify isolates to the species
      level and characterize them for carriage of 12 virulence determinants. Antibiotic
      resistance was evaluated phenotypically. Enterococcus faecalis (36.4%),
      Enterococcus faecium (9.3%) and Enterococcus durans (8.5%) were the major
      enterococci species isolated. Enterococci carrying more than two virulence
      determinants were more frequently detected in the summer (59.6%) than in other
      seasons (<= 37.6%). Very few isolates (<= 2.0%) were resistant to category I
      antibiotics ciprofloxacin and vancomycin. CONCLUSIONS: Comparison of major water
      enterococci species with major faecal enterococci species obtained from various
      host groups (human, domesticated mammals and birds, wildlife) in this drainage
      basin suggest that water enterococci may have varied faecal origins. The low
      level of antibiotic resistance among enterococci suggests that dispersion of
      antibiotic resistance via waterborne enterococci in this watershed is not
      significant. SIGNIFICANCE AND IMPACT OF THE STUDY: The data obtained in this
      study suggests that water enterococci in the SNR have a faecal origin and that
      their potential impact on public health regarding antibiotic resistance and
      virulence determinants is minimal.

PMID- 21091593
TI  - Derepression of a baker's yeast strain for maltose utilization is associated with
      severe deregulation of HXT gene expression.
AB  - AIMS: We undertook to improve an industrial Saccharomyces cerevisiae strain by
      derepressing it for maltose utilization in the presence of high glucose
      concentrations. METHODS AND RESULTS: A mutant was obtained from an industrial S.
      cerevisiae strain following random UV mutagenesis and selection on maltose/5
      thioglucose medium. The mutant acquired the ability to utilize glucose
      simultaneously with maltose and possibly also sucrose and galactose. Aerobic
      sugar metabolism was still largely fermentative, but an enhanced respirative
      metabolism resulted in a 31% higher biomass yield on glucose. Kinetic
      characterization of glucose transport in the mutant revealed the predominance of
      the high-affinity component. Northern blot analysis showed that the mutant strain
      expresses only the HXT6/7 gene irrespective of the glucose concentration in the
      medium, indicating a severe deregulation in the induction/repression pathways
      modulating HXT gene expression. Interestingly, maltose-grown cells of the mutant
      display inverse diauxy in a glucose/maltose mixture, preferring maltose to
      glucose. CONCLUSION: In the mutant here reported, the glucose transport step
      seems to be uncoupled from downstream regulation, because it seems to be unable
      to sense abundant glucose, via both repression and induction pathways.
      SIGNIFICANCE AND IMPACT OF THE STUDY: We report here the isolation of a S.
      cerevisiae mutant with a novel derepressed phenotype, potentially interesting for
      the industrial fermentation of mixed sugar substrates.

PMID- 21091594
TI  - Constitutive expression of Vitreoscilla haemoglobin in Sphingomonas elodea to
      improve gellan gum production.
AB  - AIMS: To improve a commercially used strain for gellan production by exogenous
      Vitreoscilla haemoglobin (VHb). METHODS AND RESULTS: VHb gene was expressed in
      Sphingomonas elodea under the control of constitutive bla promoter. Biochemical
      activity of expressed VHb was confirmed by CO-difference spectra analysis that
      exhibited a characteristic absorption maximum at 419 nm. During cultivation, not
      only enhanced cell growth was detected, but also 20% improvement in gellan
      production was observed after 48 h of incubation, with a maximum yield of 16.82 g
      l(-1). Moreover, maximum sucrose conversion efficiency (g gellan per g sucrose)
      was 57.8, 20% higher than that of the parental strain. We further examined the
      polysaccharide production of VHb-expressing strain at different aeration levels
      in Erlenmeyer flasks. Again, in all cases, a significant enhancement of gellan
      production was observed, and the enhancement was more significant under oxygen
      limiting conditions (up to 26.8%). CONCLUSIONS: VHb exhibited positive effect on
      cell growth and gellan yield of S. elodea, especially under hypoxic conditions.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first application of VHb as an
      effective metabolic engineering strategy in S. elodea to regulate cell growth and
      optimize gellan yield.

PMID- 21091595
TI  - Dosing strategies for conversion of haemodialysis patients from short-acting
      erythropoiesis stimulating agents to once-monthly C.E.R.A.: experience from the
      MIRACEL study.
AB  - AIMS: To analyse the impact of dosing decisions for continuous erythropoietin
      receptor activator (C.E.R.A.), a continuous erythropoietin receptor activator.
      METHODS: This was a prospective, multicentre, single-arm study in haemodialysis
      patients receiving epoetin alfa/beta or darbepoetin alfa. After a 2-month
      screening phase, patients were converted to monthly C.E.R.A. using pre-filled
      syringes during a 5-month titration phase and a 2-month evaluation phase.
      RESULTS: Four hundred and twenty-four eligible patients were converted to
      C.E.R.A. Mean Hb were 11.7 +/- 0.7, 11.7 +/- 0.8 and 11.5 +/- 0.8 g/dl during
      screening, titration and evaluation, respectively. C.E.R.A. starting dose was 125
      MUg (n = 311) or 200 MUg (n = 106), with corresponding final doses of 129 +/- 61
      MUg and 203 +/- 58 MUg. The mean number of C.E.R.A. dose decreases and increases
      were 0.9 +/- 1.0 and 1.1 +/- 1.0 per patient, respectively. Hb rarely exceeded
      12.5 g/dl after a C.E.R.A. dose increase (< 8%) and remained >= 11 g/dl after a
      dose reduction on approximately three-quarters of occasions. Among the 53
      occasions where Hb decreased >= 2 g/dl between two consecutive visits, the
      previous dose had been withheld (n = 9), concomitant blood loss, coagulopathy or
      infection was present (n = 13), or iron parameters were low (n = 17). There were
      104 adverse events/month during screening, and 45/month during the
      titration/evaluation phases. Serious adverse events occurred in 18.0 and 21.0
      patients/month during the screening and titration/evaluation phases,
      respectively. CONCLUSION: Switching haemodialysis patients from shorter-acting
      ESA to once-monthly C.E.R.A. using pre-filled syringes is straightforward, and Hb
      levels remain stable. Starting dose recommendations and dose changes correlated
      well with the clinical setting. Collateral factors such as infection or
      aggravating concomitant medical conditions should be taken into account.

PMID- 21091596
TI  - Effects on blood pressure and cardiovascular risk of variations in patients'
      adherence to prescribed antihypertensive drugs: role of duration of drug action.
AB  - AIM: To determine the effects of imperfect adherence (i.e. occasionally missing
      prescribed doses), and the influence of rate of loss of antihypertensive effect
      during treatment interruption, on the predicted clinical effectiveness of
      antihypertensive drugs in reducing mean systolic blood pressure (SBP) and
      cardiovascular disease (CVD) risk. METHOD: The effects of imperfect adherence to
      antihypertensive treatment regimens were estimated using published patterns of
      missed doses, and taking into account the rate of loss of antihypertensive effect
      when doses are missed (loss of BP reduction in mmHg/day; the off-rate), which
      varies between drugs. Outcome measures were the predicted mean SBP reduction and
      CVD risk, determined from the Framingham Risk Equation for CVD. RESULTS: In
      patients taking 75% of prescribed doses (typical of clinical practice), only long
      acting drugs with an off-rate of ~1 mmHg/day were predicted to maintain almost
      the full mean SBP-lowering effect throughout the modelled period. In such
      patients, using shorter-acting drugs (e.g. an off-rate of ~5-6 mmHg/day) was
      predicted to lead to a clinically relevant loss of mean SBP reduction of > 2
      mmHg. This change also influenced the predicted CVD risk reduction; in patients
      with a baseline 10-year CVD risk of 27.0% and who were taking 75% of prescribed
      doses, a difference in off-rate from 1 to 5 mmHg/day led to a predicted 0.5%
      absolute increase in 10-year CVD risk. CONCLUSIONS: In patients who occasionally
      miss doses of antihypertensives, modest differences in the rate of loss of
      antihypertensive effect following treatment interruption may have a clinically
      relevant impact on SBP reduction and CVD risk. While clinicians must make every
      effort to counsel and encourage each of their patients to adhere to their
      prescribed medication, it may also be prudent to prescribe drugs with a low off
      rate to mitigate the potential consequences of missing doses.

PMID- 21091597
TI  - Cloning of the unculturable parasite Pasteuria ramosa and its Daphnia host
      reveals extreme genotype-genotype interactions.
AB  - The degree of specificity in host-parasite interactions has important
      implications for ecology and evolution. Unfortunately, specificity can be
      difficult to determine when parasites cannot be cultured. In such cases, studies
      often use isolates of unknown genetic composition, which may lead to an
      underestimation of specificity. We obtained the first clones of the unculturable
      bacterium Pasteuria ramosa, a parasite of Daphnia magna. Clonal genotypes of the
      parasite exhibited much more specific interactions with host genotypes than
      previous studies using isolates. Clones of P. ramosa infected fewer D. magna
      genotypes than isolates and host clones were either fully susceptible or fully
      resistant to the parasite. Our finding enhances our understanding of the
      evolution of virulence and coevolutionary dynamics in this system. We recommend
      caution when using P. ramosa isolates as the presence of multiple genotypes may
      influence the outcome and interpretation of some experiments.

PMID- 21091599
TI  - Theileria annulata promotes Src kinase-dependent host cell polarization by
      manipulating actin dynamics in podosomes and lamellipodia.
AB  - Theileria annulata is an intracellular protozoan parasite that infects B cells
      and macrophages of ruminants. Macrophages infected with T. annulata are de
      differentiated and display tumour cell properties and a metastatic behaviour. How
      parasitized cells adapt their morphology, motility and invasive behaviour has not
      yet been addressed in detail. In this study, I investigated the regulation of
      host cell actin dynamics in T. annulata-transformed macrophages and how this
      affects host cell morphology and motility. T. annulata was found to promote the
      formation of filamentous-actin-rich podosome-type adhesions (PTAs) and
      lamellipodia, and to establish a polarized morphology of the infected cell.
      Characteristic for parasite-dependent host cell polarization is that infected
      cells display a single, persistent lamellipodium. Src kinases--in particular Hck-
      are required for the polar extension of this lamellipodium. Hck does so by
      promoting the clustered assembly of PTAs and accumulation of proteins of the
      Ezrin, Radixin, Moesin (ERM) family in lamellipodia. Polar accumulation of PTAs
      and ERM proteins correlates with focal matrix degradation underneath
      lamellipodia. These findings suggest that T. annulata equips its host cell with
      properties to adhere and invade. These properties are likely to promote the
      motile behaviour required for dissemination of infected cells in vivo.

PMID- 21091598
TI  - Attenuation of host NO production by MAMPs potentiates development of the host in
      the squid-vibrio symbiosis.
AB  - Bacterial pathogens typically upregulate the host's production of nitric oxide
      synthase (NOS) and nitric oxide (NO) as antimicrobial agents, a response that is
      often mediated by microbe-associated molecular patterns (MAMPs) of the pathogen.
      In contrast, previous studies of the beneficial Euprymna scolopes/Vibrio fischeri
      symbiosis demonstrated that symbiont colonization results in attenuation of host
      NOS/NO, which occurs in high levels in hatchling light organs. Here, we sought to
      determine whether V. fischeri MAMPs, specifically lipopolysaccharide (LPS) and
      the peptidoglycan derivative tracheal cytotoxin (TCT), attenuate NOS/NO, and
      whether this activity mediates the MAMPs-induced light organ morphogenesis. Using
      confocal microscopy, we characterized levels of NOS with immunocytochemistry and
      NO with a NO-specific fluorochrome. When added exogenously to seawater containing
      hatchling animals, V. fischeri LPS and TCT together, but not individually,
      induced normal NOS/NO attenuation. Further, V. fischeri mutants defective in TCT
      release did not. Experiments with NOS inhibitors and NO donors provided evidence
      that NO mediates apoptosis and morphogenesis associated with symbiont
      colonization. Attenuation of NOS/NO by LPS and TCT in the squid-vibrio symbiosis
      provides another example of how the host's response to MAMPs depends on the
      context. These data also provide a mechanism by which symbiont MAMPs regulate
      host development.

PMID- 21091600
TI  - Laparoscopic-monitored colonoscopic polypectomy: a multimodality method to avoid
      segmental colon resection.
AB  - AIM: In some patients with adenoma, snare polypectomy may be technically
      impossible owing to angulation of the colon or after previous surgery. This may
      result in a segmental colonic resection, if malignant invasion is thought to be
      likely. Laparoscopic mobilization of the colon to enable a simultaneous
      colonoscopy can avoid this difficulty. METHOD: A feasibility study was performed
      in 11 patients for whom endoscopic removal was technically impossible due to
      fibrosis after previous surgery or to anatomical difficulty. In 10, adenoma
      (histologically benign) had been diagnosed during diagnostic colonoscopy and in
      the remaining patient the indication was rectal bleeding. RESULTS: It was
      possible to perform a full colonoscopy after laparoscopic mobilization in all
      cases. In nine of the 10 patients with adenoma 11 tubulovillous adenomas were
      removed endoscopically, and in one the tumour was too large for endoscopic
      resection even after full mobilization. A laparoscopic segmental resection was
      performed in this case. In the patient with rectal bleeding, colonoscopy revealed
      an angiodysplasia of the caecum, also treated by resection. Apart from the two
      patients having resection, all patients were discharged within 24 h of the
      procedure. During endoscopic follow up (4-27 months) there were no recurrences.
      CONCLUSIONS: Combined laparoscopy and endoscopy enabled removal of adenomas
      otherwise inaccessible for endoscopic techniques. Thus, segmental colon
      resections can be avoided in most of these patients.

PMID- 21091601
TI  - Travel for HIV care in England: a choice or a necessity?
AB  - OBJECTIVES: The aims of the study were (1) to measure the distance required to
      travel, and the distance actually travelled, to HIV services by HIV-infected
      adults, and (2) to calculate the proportion of patients who travelled beyond
      local services and identify socio-demographic and clinical predictors of use of
      non-local services. METHODS: The straight-line distance between a patient's
      residence and HIV services was determined for HIV-infected patients in England in
      2007. 'Local services' were defined as the closest HIV service to a patient's
      residence and other services within an additional 5 km radius. Multivariable
      logistic regression was used to identify socio-demographic and clinical
      predictors of accessing non-local services. RESULTS: In 2007, nearly 57 000
      adults with diagnosed HIV infection accessed HIV services in England; 42% lived
      in the most deprived areas. Overall, 81% of patients lived within 5 km of a
      service, and 8.7% used their closest HIV service. The median distance to the
      closest HIV service was 2.5 km [interquartile range (IQR) 1.5-4.2 km] and the
      median actual distance travelled was 4.8 km (IQR 2.5-9.7 km). A quarter of
      patients used a 'non-local' service. Patients living in the least deprived areas
      were twice as likely to use non-local services as those living in the most
      deprived areas [adjusted odds ratio (AOR) 2.16; 95% confidence interval (CI) 1.98
      2.37]. Other predictors for accessing non-local services included living in an
      urban area (AOR 0.77; 95% CI 0.69-0.85) and being diagnosed more than 12 months
      (AOR 1.48; 95% CI 1.38-1.59). CONCLUSION: In England, 81% of HIV-infected
      patients live within 5 km of HIV services and a quarter of HIV-infected adults
      travel to non-local HIV services. Those living in deprived areas are less likely
      to travel to non-local services.

PMID- 21091602
TI  - In silico analysis reveals multiple putative type VI secretion systems and
      effector proteins in Pseudomonas syringae pathovars.
AB  - Type VI secretion systems (T6SS) of Gram-negative bacteria form injectisomes that
      have the potential to translocate effector proteins into eukaryotic host cells.
      In silico analysis of the genomes in six Pseudomonas syringae pathovars revealed
      that P. syringae pv. tomato DC3000, pv. tabaci ATCC 11528, pv. tomato T1 and pv.
      oryzae 1-6 each carry two putative T6SS gene clusters (HSI-I and HSI-II; HSI: Hcp
      secretion island), whereas pv. phaseolicola 1448A and pv. syringae B728 each
      carry one. The pv. tomato DC3000 HSI-I and pv. tomato T1 HSI-II possess a highly
      similar organization and nucleotide sequence, whereas the pv. tomato DC3000, pv.
      oryzae 1-6 and pv. tabaci 11528 HSI-II are more divergent. Putative effector
      orthologues vary in number among the strains examined. The Clp-ATPases and IcmF
      orthologues form distinct phylogenetic groups: the proteins from pv. tomato
      DC3000, pv. tomato T1, pv. oryzae and pv. tabaci 11528 from HSI-II group together
      with most orthologues from other fluorescent pseudomonads, whereas those from pv.
      phaseolicola, pv. syringae, pv. tabaci, pv. tomato T1 and pv. oryzae from HSI-I
      group closer to the Ralstonia solanacearum and Xanthomonas orthologues. Our
      analysis suggests multiple independent acquisitions and possible gene
      attrition/loss of putative T6SS genes by members of P. syringae.

PMID- 21091603
TI  - Personality and social context.
AB  - There has been considerable interest among biologists in the phenomenon of non
      human animal personality in recent years. Consistent variations among individuals
      in their behavioural responses to ecologically relevant stimuli, often relating
      to a trade-off between level of risk and reward, have been recorded in a wide
      variety of species, representing many animal taxa. Research into behavioural
      variation among individuals has major implications for our understanding of
      ecological patterns and processes at scales from the level of the individual to
      the level of the population. Until recently, however, many studies that have
      considered the broader ecological implications of animal personality have failed
      to take into account the crucial moderating effect of social context. It is well
      documented that social processes, such as conformity and facilitation, exert
      considerable influence on the behaviour of grouping animals and hence that
      isolated individuals may often behave in a qualitatively as well as
      quantitatively different manner to those in groups. Recently, a number of studies
      have begun to address aspects of this gap in our knowledge and have provided
      vital insights. In this review we examine the state of our knowledge on the
      relationship between individual personality and sociality. In doing so we
      consider the influence of the social context on individual personality responses,
      the interaction between the collective personalities of group members and the
      expression of those personalities in the individual, and the influence of the
      personalities of group members on group structure and function. We propose key
      areas of focus for future studies in order to develop our understanding of this
      fundamentally important area.

PMID- 21091604
TI  - Chronic heart disease and severe obstetric morbidity among hospitalisations for
      pregnancy in the USA: 1995-2006.
AB  - OBJECTIVES: to describe changes in characteristics of delivery and postpartum
      hospitalisations with chronic heart disease from 1995 to 2006. DESIGN: cross
      sectional study. SETTING: USA, nationwide hospital discharge data. POPULATION: a
      total of 47 882 817 delivery hospitalisations and 660 038 postpartum
      hospitalisations. METHODS: adjusted odds ratios describing the associations
      between chronic maternal heart disease and severe obstetric complications were
      obtained from multivariable logistic models. The contribution of chronic heart
      disease to severe morbidity was estimated using adjusted population-attributable
      fractions. MAIN OUTCOME MEASURES: prevalence and trends in chronic heart disease,
      rate and risk of severe obstetric complications. RESULTS: in 2004-2006, about
      1.4% of delivery hospitalisations were complicated with chronic heart disease. No
      substantial changes in the overall prevalence of chronic heart disease among
      hospitalisations for delivery were observed from 1995-1997 to 2004-2006. Even so,
      a linear increase was found for specific congenital heart disease, cardiac
      dysrhythmias, and cardiomyopathy and congestive heart failure (P < 0.01). During
      this same period the rate of postpartum hospitalisations with chronic heart
      disease tripled (P < 0.01). Severe complications during hospitalisations for
      delivery among women with chronic heart disease were more common in 2004-2006
      than in 1995-1997. In 2004-2006, 64.5% of the cases of acute myocardial
      infarction, 57.5% of the instances of cardiac arrest/ventricular fibrillation,
      27.8% of in-hospital mortality and 26.0% of the cases of adult respiratory
      distress syndrome were associated with hospitalisations with chronic heart
      disease. CONCLUSIONS: in the USA chronic heart disease among women hospitalised
      during pregnancy may have increased in severity from 1995 to 2006.

PMID- 21091606
TI  - Detection of myocardial ischaemia using surface microdialysis on the beating
      heart.
AB  - Microdialysis (MD) can be used to study metabolism of the beating heart. We
      investigated whether microdialysis results obtained from epicardial (surface)
      sampling reflect acute changes in the same way as myocardial sampling from within
      the substance of the ventricular wall. In anaesthetized open-thorax pigs a
      coronary snare was placed. One microdialysis probe was placed with the sampling
      membrane intramyocardially (myocardial), and a second probe was placed with the
      sampling membrane epicardially (surface), both in the area which was made
      ischaemic. Ten minutes collection intervals were used for microdialysis samples.
      Samples from 19 pigs were analysed for lactate, glucose, pyruvate and glycerol
      during equilibration, baseline, ischaemia and reperfusion periods. For both
      probes (surface and myocardial), a total of 475 paired simultaneous samples were
      analysed. Results from analyses showed no differences in relative changes for
      glucose, lactate and glycerol during baseline, ischaemia and reperfusion. Surface
      microdialysis sampling is a new application of the microdialysis technique that
      shows promise and should be further studied.

PMID- 21091605
TI  - Altered mitochondrial regulation in quadriceps muscles of patients with COPD.
AB  - Evidence exists for locomotor muscle impairment in patients with chronic
      obstructive pulmonary disease (COPD), including fiber type alterations and
      reduced mitochondrial oxidative capacity. In this study high-resolution
      respirometry was used to quantify oxygen flux in permeabilized fibres from
      biopsies of the vastus lateralis muscle in patients with COPD and compared to
      healthy control subjects. The main findings of this study were that (i) routine
      state 2 respiration was higher in COPD; (ii) state 3 respiration in the presence
      of ADP was similar in both groups with substrate supply of electrons to complex I
      (COPD 38.28 +/- 3.58 versus control 42.85 +/- 3.10 pmol s(-1) mg tissue(-1) ),
      but O(2) flux with addition of succinate was lower in COPD patients (COPD 63.72
      +/- 6.33 versus control 95.73 +/- 6.53 pmol s(-1) mg tissue(-1) ); (iii) excess
      capacity of cytochrome c oxidase in COPD patients was only ~50% that of control
      subjects. These results indicate that quadriceps muscle mitochondrial function is
      altered in patients with COPD. The regulatory mechanisms underlying these
      functional abnormalities remain to be uncovered.

PMID- 21091607
TI  - Determinants of right ventricular failure in patients admitted with acute left
      heart failure.
AB  - Pulmonary hypertension, which may lead to right ventricular (RV) failure,
      increases with left ventricular (LV) diastolic dysfunction severity. The
      prevalence and determinants of RV failure were analyzed in 120 patients admitted
      with acute left heart (LH) failure. Patients were divided into RV failure (n=50)
      and non-RV failure (n=70) groups. The prevalence of RV failure was found to be
      42%. In both groups, two thirds of the patients had isolated LV diastolic
      dysfunction and the rest had combined LV systolic and diastolic dysfunction.
      Patients in the RV failure group were characterized by higher LV diastolic grade
      (2.2 +/- 0.6 vs 1.84 +/- 0.7; P=.0070), pulmonary artery systolic pressure (PASP;
      57.8 +/- 15.3 vs 50.14 +/- 12.1 mm Hg; P=.0028), right atrial enlargement (92% vs
      25.7%; P=.000001), and more-than-moderate tricuspid regurgitation (58% vs 27.1%;
      P=.0006). RV failure is a frequent finding in patients with advanced LH failure.
      It is strongly associated with the severity of LV diastolic dysfunction and the
      severity of PASP.

PMID- 21091608
TI  - Noninvasive prediction of left ventricular systolic dysfunction in patients with
      clinically suspected heart failure using acoustic cardiography.
AB  - The signs and symptoms of systolic heart failure are frequently insensitive and
      nonspecific, making an accurate bedside diagnosis of left ventricular systolic
      dysfunction (LVSD) challenging. B-type natriuretic peptide (BNP) is often used,
      but is not diagnostically useful when in the indeterminate range. The authors
      investigated the diagnostic test characteristics of acoustic cardiographic
      parameters to identify patients with LVSD. Four hundred thirty-three patients
      with contemporaneous measurements of computerized acoustic cardiography, BNP, and
      echocardiography were included. The acoustic cardiographic model outperformed BNP
      alone at detecting reduced left ventricular ejection fraction (C statistic, 0.88
      vs 0.67; P<.0001). The acoustic model with BNP did not perform better than the
      acoustic model alone (P=.14). Within the indeterminate BNP range, the acoustic
      model outperformed BNP (C statistic, 0.89 vs 0.64; P<.0001). Noninvasive
      computerized acoustic cardiography predicted LVSD in a diverse population. This
      acoustic cardiographic model outperformed BNP alone for predicting LVSD.

PMID- 21091610
TI  - Reduced confounding by impaired ventilatory function with oxygen uptake
      efficiency slope and VE/VCO2 slope rather than peak oxygen consumption to assess
      exercise physiology in suspected heart failure.
AB  - Heart failure and ventilatory disease often coexist; both create abnormalities in
      cardiopulmonary exercise test measurements. The authors evaluated the relative
      dependency of a well-recognized index of heart failure, peak oxygen consumption
      (VO(2)), and 2 newer indices, the minute ventilation (VE)/carbon dioxide
      production (VCO(2)) slope and oxygen uptake efficiency slope (OUES), on standard
      markers of impaired cardiac and ventilatory function. One hundred twenty-four
      patients (median age, 65.8; range, 22.6-84.9), with functional limitation from
      clinical heart failure were exercised. Peak VO(2) was 17.14 +/- 7.58 mL/kg/min,
      VE/VCO(2) slope 50.1 +/- 20.1, OUES 1.46 +/- 0.68 L/min, and forced expiratory
      volume in 1 second (FEV(1) ) 1.88 +/- 0.75 L. Peak VO(2) is substantially more
      sensitive to FEV(1) than ejection fraction (4.0 mL/kg/min difference between
      above- and below-median FEV(1) and 1.5 mL/kg/min between above- and below-median
      ejection fraction). OUES does not share this peculiar excess sensitivity to
      FEV(1) (0.12 L/min difference between above- and below-median FEV(1) and 0.01
      L/min between above- and below-median ejection fraction). VE/VCO(2) slope has a
      borderline effect by FEV(1) (7.07 difference between above- and below-median
      FEV(1) and 2.07 between above- and below-median ejection fraction). Although
      widely used as a marker of heart failure severity, peak VO(2) is very sensitive
      to spirometry status and is indeed more affected by FEV(1) than by ejection
      fraction. OUES in contrast does not show this preferential sensitivity to
      impaired FEV(1).

PMID- 21091609
TI  - Peak cardiac power measured noninvasively with a bioreactance technique is a
      predictor of adverse outcomes in patients with advanced heart failure.
AB  - Peak oxygen consumption (VO(2) ) during cardiopulmonary exercise testing (CPET)
      is a powerful predictor of survival, providing an indirect assessment of cardiac
      output (CO). Noninvasive indices of CO derived from bioreactance methodology
      would add significantly to peak VO(2) as a means of risk-stratifying patients
      with heart failure. In this study, 127 patients (53 +/- 14 years of age, 66%
      male) with heart failure and an average ejection fraction of 31% +/- 15%
      underwent symptom-limited CPET using a bicycle ergometer while measuring CO
      noninvasively by a bioreactance technique. Peak cardiac power was derived from
      the product of the peak mean arterial blood pressure and CO divided by 451.
      Follow-up averaged 404 +/- 179 days (median, 366 days) to assess endpoints
      including death (n=3), heart transplant (n=10), or left ventricular assisted
      device implantation (n=2). Peak VO(2) and peak power had similar areas under the
      curve (0.77 and 0.76), which increased to 0.83 when combined. Kaplan-Meier
      cumulative survival curves demonstrated different outcomes in the subgroup with a
      VO(2) <14 mL/kg/min when stratified by a cardiac power above or below 1.5 W
      (92.2% vs 82.1% at 1 year and 81.6% vs 58.3% at last follow-up, P=.02 by log-rank
      test). Among patients with heart failure, peak cardiac power measured with
      bioreactance methodology and peak VO(2) had similar associations with adverse
      outcomes and peak power added independent prognostic information to peak VO(2) in
      those with advanced disease (eg, VO(2) <14 mL/kg/min).

PMID- 21091611
TI  - Double-blind placebo-controlled comparison of enoximone and dobutamine infusions
      in patients with moderate to severe chronic heart failure.
AB  - Few data exist on the safety of transferring patients to standard oral therapy
      for chronic heart failure (CHF) after acute management with inotropic agents.
      This study compares hemodynamic responses and cardiac dysrhythmic effects of
      continuous infusion of enoximone, dobutamine, or placebo in patients with
      moderate to severe CHF. The authors enrolled 136 patients who were randomly
      assigned to either open-label dobutamine or double-blind enoximone vs placebo.
      After 24 hours of treatment, the study was unblinded. Patients receiving placebo
      completed the study. Patients receiving enoximone or dobutamine received the
      infusion for an additional 24 hours and were then switched to standard oral
      therapy for 72 hours. Compared with placebo, both enoximone and dobutamine
      increased cardiac index and decreased pulmonary capillary wedge pressure (PCWP).
      Compared with dobutamine, enoximone significantly increased cardiac index after
      the first 24 hours of infusion and significantly decreased PCWP throughout the
      infusion period. There was no difference in the incidence of arrhythmias between
      enoximone and dobutamine. More patients (65%) tolerated the switch to oral
      therapy in the enoximone group compared with dobutamine (49%; P =.12). Enoximone
      is effective in improving the hemodynamics in patients with moderate to severe
      CHF and is tolerated at least as well as dobutamine.

PMID- 21091612
TI  - Prevalence, prognosis, and therapeutic implications of unrecognized left
      ventricular systolic dysfunction in patients with anemia and chronic kidney
      disease.
AB  - The prevalence and outcomes of unrecognized left ventricular dysfunction (ULVSD)
      in patients with anemia and chronic kidney disease (CKD) is not known. The
      authors determined whether anemia (hemoglobin <13 g/L) and CKD (glomerular
      filtration rate <60 mL/min) are risk factors for ULVSD (ejection fraction <35%,
      no known heart failure [HF]) and to determine its impact on clinical outcomes. A
      total of 1358 patients without history of HF undergoing gated myocardial
      perfusion single photon emission computed tomography for evaluation of suspected
      coronary artery disease were followed for a mean of 2.15 +/- 0.8 years. End
      points were death and heart failure hospitalization (HFH). Patients were divided
      into 4 groups (I: no anemia/no CKD, n=752; II: CKD/no anemia, n=285; III:
      anemia/no CKD, n=153; IV: anemia+CKD, n=168). Compared with group I, LVSD was
      significantly more common in group IV (11.3% vs 4%; P=.0009). Death and HFH were
      significantly higher in group IV compared with group I (death rate for group I:
      3.5% per year vs group IV: 12% per year; P<.0001) (HFH rate for group I: 1.5% per
      year vs group IV: 8% per year, P<.0001). Among patients with ejection fraction
      <35%, presence of anemia+CKD was associated with a relative risk of 2.48 (95%
      confidence interval, 1.13-5.4; P=.02) for death compared with group I. Among
      patients with ULVSD, only 65% were taking angiotensin enzyme
      inhibitors/angiotensin receptor blockers and beta-blockers. ULVSD was almost 3
      times more common in patients with anemia+CKD compared with those without and was
      associated with a significantly higher risk of death and HFH. It may therefore be
      beneficial to screen patients with anemia and CKD for ULVSD, since early therapy
      may improve outcomes.

PMID- 21091613
TI  - Prevalence of vaccination rates in systolic heart failure: a prospective study of
      549 patients by age, race, ethnicity, and sex in a heart failure disease
      management program.
AB  - Healthy People 2010 aims at immunizing 60% of high-risk adults annually against
      influenza and once against pneumococcal disease. The aim of this study was to
      evaluate the use of a standardized approach to improve vaccination rates in
      patients with heart failure (HF); to determine whether disparities exist based on
      age, race, ethnicity, or sex at baseline and follow-up; and to evaluate the
      impact of clinical variables on the odds of being vaccinated. A prospective study
      of 549 indigent patients enrolled in a systolic HF disease management program
      (HFDMP) began enrollment from August 2007 to January 2009 at Jackson Memorial
      Hospital. Patients were interviewed at their initial visit for immunization
      status; those without vaccinations were offered the vaccines. Prevalence of
      vaccination (POV) for influenza and pneumococcal disease was obtained at baseline
      and at follow-up. The odds ratio for being vaccinated was calculated using
      logistic regression. The study population comprised mostly Hispanic (56%), black
      (37%), and male (70%) patients, with a mean age of 56 +/- 12 years and a mean
      ejection fraction of 25% +/- 10%. The initial POV for both was 22% at baseline.
      At follow-up, POV improved to 60.5%. Of those not vaccinated at baseline, 17.5%
      refused vaccination. Odds ratios at baseline for age, race/ethnicity, and sex
      were 0.99 (P=.99), 0.63 (P=.08), and 0.62 (P=.14), respectively. These did not
      change significantly at follow-up. Prevalence of vaccination in our cohort was
      low. Enrollment into the HFDMP improved immunization prevalence without creating
      age, race, ethnicity, or sex disparities.

PMID- 21091614
TI  - Reverse or inverted takotsubo cardiomyopathy (reverse left ventricular apical
      ballooning syndrome) presents at a younger age compared with the mid or apical
      variant and is always associated with triggering stress.
AB  - Takotsubo cardiomyopathy is usually caused by triggering stress. It has 4
      different subtypes. There has been no consensus to differentiate various types
      with regard to characteristics of the patient population. The goal of this study
      was to evaluate any clinical differences between the reverse type in comparison
      to common apical and mid-cavitary types using case series of reported cases. The
      authors searched published articles in PubMed and Medline on takotsubo or stress
      induced cardiomyopathy. They included only cases that reported different types of
      takotsubo cardiomyopathy with baseline clinical characteristics. They identified
      60 patients for the final analysis. The types of takotsubo cardiomyopathy seen in
      this study are classified as classic (66.7%), mid-cavitary (10%), or reverse
      (inverted) (23.3%). Patients with reverse-type takotsubo cardiomyopathy were
      significantly younger compared with those with other types (mean age, 36 for
      reverse vs 62 for other types; P<.001). Furthermore, all patients with the
      reverse type had physical or mental stress, whereas those with other types had no
      triggering stress in 02% of the reported cases (P<.0001). Among patients
      presenting with takotsubo cardiomyopathy, the reverse or inverted variant
      presents at a younger age and is always associated with a triggering of emotional
      or physical stress.

PMID- 21091615
TI  - Differentiating pulmonary arterial and pulmonary venous hypertension and the
      implications for therapy.
AB  - Pulmonary arterial and pulmonary venous hypertension develop from distinctly
      different etiologies. Pulmonary arterial hypertension (PAH), or Group 1 pulmonary
      hypertension (PH), is a precapillary PH that arises idiopathically or as the
      result of a divergent array of causes, including connective tissue disease.
      Pulmonary venous hypertension (PVH), or Group 2 PH, primarily manifests as a
      postcapillary PH in the setting of left heart failure or valvular disease. A
      subset of PVH patients, however, develop a reactive precapillary component of PH
      that mimics PAH. These patients can be misdiagnosed as having Group 1 PH by 2
      dimensional echocardiography and are sometimes treated as such, which leads to
      exacerbation of heart failure. Therefore, 2-dimensional or Doppler
      echocardiography alone cannot be used to differentiate between these two
      classifications of PH. This highlights the need for right heart catheterization
      in the clinical assessment and diagnostic work-up of PH. The combination of
      imaging and invasive hemodynamic assessment by right heart catheterization
      provides the best diagnostic approach to ensure proper delineation of pulmonary
      arterial and pulmonary venous hypertension, and in turn leads to appropriate
      treatment.

PMID- 21091616
TI  - Individual and joint associations of obesity and physical activity on the risk of
      heart failure.
AB  - Heart failure (HF) has become a major public health problem in both developed and
      developing countries of the world. The individual and joint associations of
      physical activity and obesity on the risk of HF have been extensively studied in
      recent years. The results from prospective studies consistently indicate that
      regular physical activity reduces the risk of HF, while both general obesity and
      abdominal obesity increase the risk of HF. Furthermore, research related to the
      joint association of obesity and physical activity on HF risk indicates that lean
      and active individuals had the lowest risk of HF. Therefore, preventing HF by
      maintaining optimal weight and engaging in regular physical activity may reduce
      the public health burden of HF worldwide.

PMID- 21091617
TI  - Closing the gap.

PMID- 21091618
TI  - Towards evidence-based management: creating an informative database of nursing
      sensitive indicators.
AB  - PURPOSE: The purpose of this paper is to describe the creation, evolution, and
      implementation of a database of nursing-sensitive and potentially nursing
      sensitive indicators, the Military Nursing Outcomes Database (MilNOD). It
      discusses data quality, utility, and lessons learned. DESIGN/METHODS: Prospective
      data collected each shift include direct staff hours by levels (i.e., registered
      nurse, other licensed and unlicensed providers), staff categories (i.e.,
      military, civilian, contract, and reservist), patient census, acuity, and
      admissions, discharges, and transfers. Retrospective adverse event data (falls,
      medication errors, and needle-stick injuries) were collected from existing
      records. Annual patient satisfaction, nurse work environment, and pressure ulcer
      and restraint prevalence surveys were conducted. FINDINGS AND CONCLUSIONS: The
      MilNOD contains shift level data from 56 units in 13 military hospitals and is
      used to target areas for managerial and clinical performance improvement. This
      methodology can be modified for use in other healthcare systems. CLINICAL
      RELEVANCE: As standard tools for evidence-based management, databases such as
      MilNOD allow nurse leaders to track the status of nursing and adverse events in
      their facilities.

PMID- 21091619
TI  - Women receiving news of a family BRCA1/2 mutation: messages of fear and
      empowerment.
AB  - PURPOSE: Communication of genetic test results to healthy at-risk family members
      is complicated considering family dynamics and the complexity of cancer genetics.
      The purpose of this study was to understand the experience of family
      communication of BRCA1/2 results from the perspective of young and middle-aged
      women receiving the news. THEORETICAL RATIONALE: Individuals are self
      interpretive beings influenced by family culture, history, and communication
      patterns. Humans express meaning through language and stories. METHODS:
      Heideggerian hermeneutics guided in-depth interviews and team interpretation of
      data. Using purposive and network sampling, 19 women 18 to 50 years of age who
      received news of a family BRCA1/2 mutation from a biologic relative were
      recruited from support groups and two health facilities in upstate New York.
      FINDINGS: Five themes emerged: (a) situating the story, (b) receiving the message
      from family, (c) responding to receipt of the message, (d) impacting family
      communication, and (e) advice for communicating risk. Two constitutive patterns
      were identified: (a) communicating risk as a message of fear and empowerment and
      (b) integrating the message by taking one step at a time.
      CONCLUSIONS/IMPLICATIONS: Healthcare professionals (HCPs) have an important role
      in provision of anticipatory guidance for communication of genetic test results,
      including the potential behavioral and emotional responses to family risk
      communication. Future research is indicated to understand the role of HCPs in
      family risk communication. CLINICAL RELEVANCE: Presentation of comprehensive and
      balanced information and the use of patient-centered communication is essential.
      HCPs need to view women as whole rather than as a person at risk. Continued
      support is needed for women who subsequently test positive or negative for the
      family BRCA1/2 mutation from HCPs and others, often outside the family network.

PMID- 21091620
TI  - Grandmothers raising grandchildren: results of an intervention to improve health
      outcomes.
AB  - PURPOSE: To examine the impact of an intervention to improve the health of
      grandmothers raising grandchildren in parent-absent homes. DESIGN: A
      longitudinal, pretest-posttest design. METHODS: The sample was composed of 529
      female caregivers with a mean age of 56.7 years (range 38-83) who were
      predominantly low-income African Americans. Data were collected prior to the
      intervention and again at 12 months when the intervention was complete. The
      intervention involved home visitation by registered nurses and social workers, as
      well as other support services. The Short Form-36 was used to assess physical and
      mental health, using eight multi-item scales. RESULTS: A comparison of pre- and
      posttest mean scores on the SF-36 indicated significantly (p < .003) improved
      mean scores for vitality, physical effects on role functioning, emotional effects
      on role functioning, and mental health. No significant differences were found for
      other attributes. CONCLUSIONS: These preliminary findings suggest that
      grandmothers raising grandchildren may benefit from a home-based intervention
      designed to improve health attributes. Implications for nursing practice, policy,
      and research are presented. CLINICAL RELEVANCE: The health of grandmother
      caregivers is critical to their ability to parent grandchildren successfully.
      Nurses practicing in a variety of settings are in a unique position to identify
      and address the health challenges of grandmothers who are raising grandchildren.

PMID- 21091621
TI  - Overweight and obesity and their correlates among Jordanian adolescents.
AB  - PURPOSE: To provide current estimates of the prevalence of overweight and obesity
      among Jordanian adolescents 14 to 17 years of age living in Irbid Governorate,
      and to determine the factors that are associated with overweight and obesity.
      DESIGN: Descriptive correlational cross-sectional design was used. METHODS: Body
      mass index, perceived stress, dietary habits, physical activity, and demographics
      of 824 Jordanian adolescents living in Irbid were measured through a multistage
      cluster sampling method. FINDINGS: The overall prevalence of overweight and
      obesity was 19.1% and 6.3%, respectively. The prevalence of overweight and
      obesity among boys was 17.2% and 5.7%, respectively, and among girls was 21.0%
      and 7.0%, respectively. Both overweight and obesity rates were higher among
      girls. Physical activity, mother's educational level, and number of family
      members were negatively correlated with overweight and obesity. On the other
      hand, eating breakfast regularly, mother's weight, consumption of fried food, and
      perceived stress level were positively correlated with overweight and obesity.
      CONCLUSIONS: Overweight and obesity are becoming a health problem among both boys
      and girls in Jordan. CLINICAL RELEVANCE: Detecting the prevalence and the
      associated factors of overweight and obesity among adolescents is the first step
      toward proposing intervention strategies.

PMID- 21091622
TI  - An integrative review of factors associated with falls during post-stroke
      rehabilitation.
AB  - PURPOSE: Our aims were to evaluate evidence of risk factors for falls among
      patients in stroke rehabilitation and to offer recommendations for clinical
      practice and future research. METHOD: We conducted an integrative review of the
      literature published from 1990 to 2009 that describes empirical investigations of
      risk factors for post-stroke falls during inpatient rehabilitation. We searched
      Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      PsycInfo, and Embase databases, using the search terms "accidental falls,""fall
      risk,""risk factors,""risk assessment,""stroke," and "cerebrovascular disorders."
      We extracted information regarding study design, sample, potential risk factors,
      analytic methods, findings, and limitations from the 14 articles that met our
      inclusion criteria, and we rated the level of evidence for each study. FINDINGS:
      Available empirical evidence points to impaired balance, visuospatial
      hemineglect, and impaired performance of activities of daily living as risk
      factors for falls during inpatient rehabilitation for stroke. Associations
      between falls and cognitive function, incontinence, visual field deficits, and
      stroke type were less clear, while relationships between falls and age, gender,
      stroke location, and impaired vision and hearing were not supported. CONCLUSIONS:
      The relatively sparse literature pertaining to risk factors for falls among
      stroke rehabilitation inpatients indicates that deficits affecting balance,
      perception, and self-care significantly increase the likelihood of falls.
      Particularly intriguing is the less well established role of post-stroke
      cognition in falls in this population. A conceptual model is needed to guide
      scientific inquiry and clinical practice in this area. CLINICAL RELEVANCE: When
      clinicians in the inpatient stroke rehabilitation setting evaluate which patients
      are at greatest risk to fall, stroke-specific risk factors such as impaired
      balance, visuospatial hemineglect, and self-care deficits may be better
      predictors than more general risk factors such as age, incontinence, and sensory
      impairments. Patients with these stroke-specific deficits may benefit from the
      use of aggressive fall prevention interventions.

PMID- 21091623
TI  - Development and evaluation of an undergraduate training course for developing
      International Council of Nurses disaster nursing competencies in China.
AB  - BACKGROUND: Nurses are often called upon to play the role of first responder when
      disaster occurs. Yet the lack of accepted competencies and gaps in education make
      it difficult to recruit nurses prepared to respond to a disaster and provide
      assistance in an effective manner. DESIGN: Based on the International Council of
      Nurses (ICN) Framework of Disaster Nursing Competencies and Global Standards for
      the Initial Education of Professional Nurses and Midwives, a training course
      titled "Introduction to Disaster Nursing" was designed and implemented with 150
      students. A pre-post survey design was used to assess changes in participants'
      self-rated disaster nursing competencies. The impact of the training course on
      participants' attitudes toward disaster nursing and their learning experience
      were also assessed. FINDINGS: All participants passed the assessments and
      examination with an average score of 70%. Pre- and posttraining self-ratings of
      the disaster nursing competencies increased from 2.09 to 3.71 (p < .001) on a
      Likert scale of 1 to 5, and the effect size was large, with Cohen's d higher than
      0.8. No significant difference in both examination results (60% group
      assignments; 40% written examination) and self-rated competencies was noted
      between the senior year students and graduate nurse participants by Mann-Whitney
      U test (p value = .90). The majority of participants indicated their willingness
      to participate as a helper in disaster relief and saw themselves competent to
      work under supervision. CONCLUSIONS: The ICN Framework of Disaster Nursing
      Competencies was instrumental to guide the training curriculum development. This
      introductory training course could be incorporated into undergraduate nursing
      education programs as well as serve as a continuing education program for
      graduate nurses. CLINICAL RELEVANCE: The training program can be used for
      preparing generalist nurses of their nursing competencies in disaster
      preparedness, response and post-disaster recovery and rehabilitation.

PMID- 21091624
TI  - Retaining nurses and other hospital workers: an intergenerational perspective of
      the work climate.
AB  - PURPOSE: This article describes and compares work climate perceptions and
      intentions to quit among three generations of hospital workers and nurses.
      BACKGROUND: Never before in history has the workplace comprised such a span of
      generations. The current workforce includes three main generations: Baby Boomers
      (born between 1946 and 1963), Generation X (born between 1964 and 1980), and
      Generation Y (born between 1981 and 2000). However, very little research has
      linked turnover among nurses and other healthcare workers to their generational
      profile. METHOD: A quantitative study with a correlational descriptive design was
      used. 1,376 hospital workers of the three generations (with 42.1% nurses, 15.6%
      support staff, 20.1% office employees, and 22.1% health professionals or
      technicians), employed in a university-affiliated hospital, completed a self
      administered questionnaire. They answered the Psychological Climate Questionnaire
      and a measure of turnover intention. RESULTS: Generation Y hospital workers
      obtained a significantly lower score on the "Challenge" scale than did Baby
      Boomers. On the "Absence of Conflict" and "Warmth" scales, the opposite occurred,
      with Baby Boomers obtaining a significantly lower score than Generation Y
      respondents. If the nurse job category is taken separately, Generation Y nurses
      expressed a negative perception of the "Goal Emphasis" scale, compared with Baby
      Boomers. The proportion of Generation Y nurses who intend to quit is almost three
      times higher than that of other hospital workers from Generation Y. The main
      reason given by workers from Generations Y and X who intend to quit the
      organization is their own career advancement. The main reason given by Baby
      Boomers who intend to quit is retirement. CONCLUSIONS: Retention strategies that
      focus on improving the work climate are beneficial to all generations of hospital
      workers and nurses. If generation-specific retention strategies are developed,
      these should focus on the three areas identified to have intergenerational
      differences: challenges, absence of conflict, and warmth. CLINICAL RELEVANCE: New
      nurses will benefit from strategies aimed at supporting their career advancement
      in the workplace.

PMID- 21091625
TI  - A comparative study of assessment grading and nursing students' perceptions of
      quality in sessional and tenured teachers.
AB  - PURPOSE: Although the global nursing faculty shortage has led to increasing
      reliance upon sessional staff, limited research has explored the impact of these
      sessional staff on the quality of teaching in higher education. We aim to examine
      differences in (a) student satisfaction with sessional and tenured staff and (b)
      assessment scores awarded by sessional and tenured staff in students' written
      assignments. DESIGN: A comparative study method was used. Participants were
      recruited from students enrolled in the three nursing practice subjects across
      the 3 years of the baccalaureate program in an Australian university during the
      second semester of 2008. METHODS: This study collected student data via an online
      version of the Perceptions of Teaching and Course Satisfaction scale and compared
      the grades awarded by sessional and tenured academics for a written assessment in
      a single assignment in each of the nursing practice subjects. Of the 2,045
      students enrolled in the nursing practice subjects across the 3 years of the
      bachelor of nursing (BN) program, 566 (28%) completed the online teaching and
      course satisfaction survey, and 1,972 assignment grades (96%) were available for
      analysis. FINDINGS: Compared with tenured academics, sessional teachers received
      higher rating on students' perception on teaching satisfaction by students in
      Year 1 (p= .021) and Year 2 (p= .002), but not by students in Year 3 (p= .348).
      Following the same trend, sessional teachers awarded higher assignment grades to
      students in Year 1 (p < .001) and Year 2 (p < .001) than tenured academics, with
      no significant disparity in grades awarded to students in Year 3. CONCLUSIONS:
      The higher grades awarded by sessional teachers to 1st- and 2nd-year students
      could be one explanation for why these teachers received higher student ratings
      than tenured teachers. Not discounting the possibility of grade inflation by
      sessional staff, it could be that tenured teachers have a higher expectation for
      the quality of students' work, and hence were more stringent in their assessment
      grading. Sessional teachers did not receive a higher rating from 3rd-year
      students, and this could be attributed to a change in student perception as they
      progress through the course, valuing a broader and more professional aspect of
      nursing knowledge, which is more likely to be the strength of tenured staff.
      CLINICAL RELEVANCE: These findings highlight a need for the development and
      implementation of strategies to facilitate the inclusion of sessional staff
      teaching in a BN program, in order to prepare graduate nurses that are well
      equipped for clinical practice.

PMID- 21091626
TI  - Translation of health surveys using mixed methods.
AB  - PURPOSE: The purpose of this study was to determine the effectiveness of a
      process-based translation method for a health survey instrument, Searching for
      Hardships and Obstacles to Shots (SHOTS), using a community-based participatory
      approach with the Hmong community. DESIGN: The study was based on a cross
      sectional survey to assess the reliability and validity of the SHOTS immunization
      survey, an instrument used in the Hmong community, who are refugees originally
      from Laos living in the United States. METHOD: Process-based universalistic
      health survey translation methods were used in a six-step procedure to translate
      the instrument. Mixed methods were used to analyze results, including cognitive
      interviewing, content validity indexing, Cronbach's alpha, t tests, and the
      Kolmogorov-Smirnov test. FINDINGS: Participants were able to accurately complete
      the SHOTS survey in either Hmong or English, depending on participant preference.
      CONCLUSIONS: Universalistic, process-based, mixed methods used to analyze
      language translation, in combination with the principles of community-based
      participatory research, provide effective methods to translate health surveys.
      Involvement of the community strengthens the quality of translation and improves
      reliability and validity of survey results. CLINICAL RELEVANCE: Healthcare
      providers require accurate and reliable information from evidence-based health
      surveys to plan for culturally responsive care. Cross-cultural research often
      relies on language translation. Translation of a health survey instrument may be
      improved with universalistic, process-based methodology.

PMID- 21091627
TI  - Coping with preclinical disability: older women's experiences of everyday
      activities.
AB  - PURPOSE: The purpose of this paper is to describe coping practices used by older
      women during preclinical disability. DESIGN: This paper was derived from
      qualitative data gathered during a larger multimethod longitudinal study. Twelve
      women (60 to 80 years of age) participated in baseline functional performance
      measures and then repeated in-depth interviews and participant observations over
      18 months. METHODS: A hermeneutic approach was used to interpret the in-depth
      interviews, participant observations, and field notes using three interrelated
      processes of thematic, exemplar, and identification of paradigm cases to identify
      coping practices. FINDINGS: Women coped with functional decline, such as
      difficulty getting up from the floor, in many different ways. Coping practices
      were grouped into five themes: resist, adapt, substitute, endure, and eliminate.
      CLINICAL RELEVANCE: These findings suggest that nurses need to realize outward
      appearances may mask the level of effort required for older women to complete
      daily activities.

PMID- 21091628
TI  - Attitudes of relatives of nursing home residents toward physical restraints.
AB  - PURPOSE: Attitudes of nursing home staff, residents, and their relatives
      determine the decision-making process about the use of physical restraints.
      Knowledge of staffs' attitudes toward physical restraints is sparse; even less is
      known about relatives' attitudes. Therefore, we surveyed relatives' attitudes and
      opinions toward physical restraints and compared the results to a survey of
      nursing home staff. DESIGN: Cross-sectional survey comparing 177 nursing home
      residents' relatives from 13 German facilities in 2008 to 258 nursing home nurses
      from 25 German facilities in 2007. METHODS: The German version of the Maastricht
      Attitude Questionnaire was administered. Part I contains 22 items with three
      subscales (reasons, consequences, and appropriateness of restraints); Part II
      contains 16 items evaluating restrictiveness and discomfort of restraint
      measures, respectively. Descriptive and explorative inferential statistics were
      used for data analyses. FINDINGS: Response rate in both samples was above 90%.
      Mean age was 62 years (SD 12.60; range 24-93) in relatives and 44 years (SD
      11.40; range 19-65) in nurses; 72% and 82% were female, respectively. Relatives
      assess physical restraints a little more positively compared to nurses, with an
      average of 3.40 (SD 0.60) versus 3.07 (SD 0.48) on a 5-point scale (5=strongly
      positive attitude). Relatives assess physical restraints as slightly less
      restrictive, with 2.11 (SD 0.33), and as less discomforting, with 2.10 (SD 0.38)
      points, compared to nursing staff, who assess the restraints' restrictiveness
      with 2.19 (SD 0.29) points and its discomfort with 2.17 (SD 0.32) on a 3-point
      scale (3=very restrictive/discomforting). Both groups consider wrist and ankle
      belts as most restrictive and uncomfortable, while sensor mats, infrared systems,
      and unilateral bedrails were rated as the lowest for restrictiveness and
      discomfort. CONCLUSIONS: Attitudes of nursing home residents' relatives toward
      physical restraints are rather positive and generally comparable with nursing
      home staffs' attitudes. CLINICAL RELEVANCE: Interventions aimed to reduce
      physical restraints need to include education of both staff and relatives of
      nursing home residents.

PMID- 21091630
TI  - Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in
      inflammatory microenvironment favours the growth of B16 melanoma cells.
AB  - Mesenchymal stem cells (MSCs) are studied for their potential clinical use in
      regenerative medicine, tissue engineering and tumour therapy. However, the
      therapeutic application of MSCs in tumour therapy still remains limited unless
      the immunosuppressive role of MSCs for tumour growth in vivo is better
      understood. In this study, we investigated the mechanism of MSCs favouring tumour
      escape from immunologic surveillance in inflammatory microenvironment. We first
      compared the promotive capacity of bone marrow-derived MSCs on B16 melanoma cells
      growth in vivo, pre-incubated or not with the inflammatory cytokines interferon
      (IFN)-gamma and tumour necrosis factor (TNF)-alpha. We showed that the
      development of B16 melanoma cells is faster when co-injected with MSCs pre
      incubated with IFN-gamma and TNF-alpha compared with control groups. Moreover,
      tumour incidence increases obviously in allogeneic recipients when B16 melanoma
      cells were co-injected with MSCs pre-incubated with IFN-gamma and TNF-alpha. We
      then demonstrated that the immunosuppressive function of MSCs was elicited by IFN
      gamma and TNF-alpha. These cytokine combinations provoke the expression of
      inducible nitric oxide synthase (iNOS) by MSCs. The impulsive effect of MSCs
      treated with inflammatory cytokines on B16 melanoma cells in vivo can be reversed
      by inhibitor or short interfering RNA of iNOS. Our results suggest that the MSCs
      in tumour inflammatory microenvironment may be elicited of immunosuppressive
      function, which will help tumour to escape from the immunity surveillance.

PMID- 21091631
TI  - Hematopoietic bone marrow cells participate in endothelial, but not epithelial or
      mesenchymal cell renewal in adult rats.
AB  - The extent to which bone marrow (BM) contributes to physiological cell renewal is
      still controversial. Using the marker human placental alkaline phosphatase (ALPP)
      which can readily be detected in paraffin and plastic sections by histochemistry
      or immunohistochemistry, and in ultrathin sections by electron microscopy after
      pre-embedding staining, we examined the role of endogenous BM in physiological
      cell renewal by analysing tissues from lethally irradiated wild-type inbred
      Fischer 344 (F344) rats transplanted (BMT) with unfractionated BM from ALPP
      transgenic F344 rats ubiquitously expressing the marker. Histochemical,
      immunohistochemical and immunoelectron microscopic analysis showed that the
      proportion of ALPP(+)  capillary endothelial cells (EC) profoundly increased from
      1 until 6 months after BMT in all organs except brain and adrenal medulla. In
      contrast, pericytes and EC in large blood vessels were ALPP(-) . Epithelial cells
      in kidney, liver, pancreas, intestine and brain were recipient-derived at all
      time-points. Similarly, osteoblasts, chondrocytes, striated muscle and smooth
      muscle cells were exclusively of recipient origin. The lack of mesenchymal BM
      derived cells in peripheral tissues prompted us to examine whether BMT resulted
      in engraftment of mesenchymal precursors. Four weeks after BMT, all
      haematopoietic BM cells were of donor origin by flow cytometric analysis, whereas
      isolation of BM mesenchymal stem cells (MSC) failed to show engraftment of donor
      MSC. In conclusion, our data show that BM is an important source of physiological
      renewal of EC in adult rats, but raise doubt whether reconstituted irradiated
      rats are an apt model for BM-derived regeneration of mesenchymal cells in
      peripheral tissues.

PMID- 21091632
TI  - Infarcted myocardium-like stiffness contributes to endothelial progenitor lineage
      commitment of bone marrow mononuclear cells.
AB  - Optimal timing of cell therapy for myocardial infarction (MI) appears during 5 to
      14 days after the infarction. However, the potential mechanism requires further
      investigation. This work aimed to verify the hypothesis that myocardial stiffness
      within a propitious time frame might provide a most beneficial physical condition
      for cell lineage specification in favour of cardiac repair. Serum vascular
      endothelial growth factor (VEGF) levels and myocardial stiffness of MI mice were
      consecutively detected. Isolated bone marrow mononuclear cells (BMMNCs) were
      injected into infarction zone at distinct time-points and cardiac function were
      measured 2 months after infarction. Polyacrylamide gel substrates with varied
      stiffness were used to mechanically mimic the infarcted myocardium. BMMNCs were
      plated on the flexible culture substrates under different concentrations of VEGF.
      Endothelial progenitor lineage commitment of BMMNCs was verified by
      immunofluorescent technique and flow cytometry. Our results demonstrated that the
      optimal timing in terms of improvement of cardiac function occurred during 7 to
      14 days after MI, which was consistent with maximized capillary density at this
      time domains, but not with peak VEGF concentration. Percentage of double-positive
      cells for DiI-labelled acetylated low-density lipoprotein uptake and fluorescein
      isothiocyanate (FITC)-UEA-1 (ulex europaeus agglutinin I lectin) binding had no
      significant differences among the tissue-like stiffness in high concentration
      VEGF. With the decrease of VEGF concentration, the benefit of 42 kPa stiffness,
      corresponding to infarcted myocardium at days 7 to 14, gradually occurred and
      peaked when it was removed from culture medium. Likewise, combined expressions of
      VEGFR2(+) , CD133(+)  and CD45(-)  remained the highest level on 42 kPa substrate
      in conditions of lower concentration VEGF. In conclusion, the optimal efficacy of
      BMMNCs therapy at 7 to 14 days after MI might result from non-VEGF dependent
      angiogenesis, and myocardial stiffness at this time domains was more suitable for
      endothelial progenitor lineage specification of BMMNCs. The results here
      highlight the need for greater attention to mechanical microenvironments in cell
      culture and cell therapy.

PMID- 21091633
TI  - The novel Aurora A kinase inhibitor MLN8237 is active in resistant chronic
      myeloid leukaemia and significantly increases the efficacy of nilotinib.
AB  - Novel therapies are urgently needed to prevent and treat tyrosine kinase
      inhibitor resistance in chronic myeloid leukaemia (CML). MLN8237 is a novel
      Aurora A kinase inhibitor under investigation in multiple phase I and II studies.
      Here we report that MLN8237 possessed equipotent activity against Ba/F3 cells and
      primary CML cells expressing unmutated and mutated forms of breakpoint cluster
      region-Abelson kinase (BCR-ABL). Notably, this agent retained high activity
      against the T315I and E255K BCR-ABL mutations, which confer the greatest degree
      of resistance to standard therapy. MLN8237 treatment disrupted cell cycle
      kinetics, induced apoptosis, caused a dose-dependent reduction in the expression
      of the large inhibitor of apoptosis protein Apollon, and produced a morphological
      phenotype consistent with Aurora A kinase inhibition. In contrast to other Aurora
      kinase inhibitors, MLN8237 did not significantly affect BCR-ABL activity.
      Moreover, inhibition of Aurora A with MLN8237 significantly increased the in
      vitro and in vivo efficacy of nilotinib. Targeted knockdown of Apollon sensitized
      CML cells to nilotinib-induced apoptosis, indicating that this is an important
      factor underlying MLN8237's ability to increase the efficacy of nilotinib. Our
      collective data demonstrate that this combination strategy represents a novel
      therapeutic approach for refractory CML that has the potential to suppress the
      emergence of T315I mutated CML clones.

PMID- 21091634
TI  - MicroRNA-196: critical roles and clinical applications in development and cancer.
AB  - The discovery of microRNAs (miRNAs) represents one of the most significant
      advances in biological and medical sciences in the last decade. Hundreds of
      miRNAs have been identified in plants, viruses, animals and human beings, and
      these tiny, non-coding RNA transcripts have been found to play crucial roles in
      important biological processes involved in human health and disease. Recently,
      many studies have demonstrated that miR-196 plays critical roles in normal
      development and in the pathogenesis of human disease processes such as cancer.
      Several investigations have implemented cell culture and animal models to explore
      the potential molecular mechanisms of miR-196. This review provides updated
      information about the structure of the miR-196 gene and the roles of miR-196 in
      development, cancer and disease formation. Importantly, we discuss the possible
      molecular mechanisms whereby miR-196 regulates cellular functions including
      targeting molecules and gene regulation pathways; potential clinical applications
      are addressed, as well as future directions for investigation. miR-196a may prove
      to be a novel therapeutic target for several cancers.

PMID- 21091636
TI  - Investigating the humoral immune response in chronic venous leg ulcer patients
      colonised with Pseudomonas aeruginosa.
AB  - The ability to manage the bioburden in chronic wounds is most likely coupled to
      the humoral immune response of the patient. We analysed markers of systemic
      immune response in patients with chronic venous leg ulcers (CVLUs) colonised (no
      systemic infection) with the opportunistic pathogen Pseudomonas aeruginosa. Sera
      from 44 clinically non infected patients with CVLUs were analysed for total IgM
      and IgG isotype 1-4, complement C3, mannose-binding lectin (MBL), interleukin
      (IL)-6, C-reactive protein (CRP) and specific anti-P. aeruginosa antibodies
      against exotoxin A, elastase and alkaline phosphatase. Concentrations of IL-6
      versus CRP intercorrelated (beta = 2.43 95% CI (1.34-4.34)), but were independent
      of P. aeruginosa colonisation. MBL deficiency (MBL < 500 ng/ml) correlated to
      high serum levels of IgG(1) (P = 0.038) consistent with a compensatory mechanism,
      but not related to presence of P. aeruginosa in the ulcers. Twenty-four patients
      (54.5%) were culture positive for P. aeruginosa, also conferring significantly
      high serum levels of complement C3 (P = 0.014), but only two of these had
      positive titres for antibodies against exotoxin A. All patient sera were negative
      for antibodies against elastase and alkaline phosphatase. Fluorescent in situ
      hybridization analysis on randomly selected culture-positive patients could not
      establish unambiguous presence of P. aeruginosa biofilms in the ulcers. A
      multiple regression model showed P. aeruginosa and systemic CRP as significant
      factors in deterioration of ulcer healing rate.

PMID- 21091635
TI  - Intragastric self-infusion of ethanol in high- and low-drinking mouse genotypes
      after passive ethanol exposure.
AB  - Two experiments examined the effect of 5 days of passive exposure to ethanol (or
      water) on later self-infusion of ethanol or water via surgically implanted
      intragastric (IG) catheters in mouse genotypes previously shown to drink high
      (C57BL/6J, HAP2) or low (DBA/2J, LAP2) amounts of ethanol in home-cage continuous
      access two-bottle choice procedures. Intragastric ethanol self-infusion was
      affected by both genotype and a history of passive ethanol exposure, with greater
      intakes in the high-drinking genotypes and in groups that received passive
      exposure to ethanol. Passive ethanol exposure also increased preference for the
      flavor that signaled ethanol infusion (S+), eliminating genetic differences in
      this measure. The increases in ethanol intake and S+ preference induced by
      ethanol exposure might have been mediated jointly by development of tolerance to
      aversive post-absorptive ethanol effects and negative reinforcement because of
      alleviation of withdrawal. Bout analyses indicated that ethanol exposure
      increased ethanol self-infusion by increasing the total number of daily bouts
      rather than by increasing bout size. These analyses also showed that DBA/2J mice
      infused larger ethanol bouts and a greater percentage of their total intakes in
      large bouts than C57BL/6J mice. Overall, these studies suggest that the IG self
      infusion procedure is a potentially useful new tool for studying genetic and
      environmental influences on excessive ethanol intake and preference in mice.

PMID- 21091638
TI  - The cadherin switch in melanoma instigated by HGF is mediated through epithelial
      mesenchymal transition regulators.

PMID- 21091639
TI  - Acupuncture for depression: a critique of the evidence base.
AB  - AIM: The aim of this review is to examine the evidence for acupuncture's
      effectiveness as a depression intervention. Unlike other reviews, which consider
      methodological concerns relevant to all experimental evaluations, this review
      focuses on the scope of studies, and uses a PICO (patients, intervention,
      comparison, and outcome) structure to determine what can potentially be learned
      from primary studies that have already been screened for methodological quality
      by reviewers. DISCUSSION: The review identified a number of study limitations.
      (i) PATIENTS: majority of trial reports have not described a rationale for the
      selection of patients or inclusion/exclusion criteria. Prognostic indicators were
      not reported and there were also concerns about the generalizability of study
      populations. (ii) INTERVENTION: most trials investigate poorly rationalized
      standardized acupuncture protocols thus quality of care may be an issue and
      generalizability to routine clinical practice is a main concern. In trials using
      other methods generalizability is also poor. (iii) Comparisons: concerns were
      raised about using therapeutically inappropriate acupuncture. (iv) OUTCOMES:
      short-term focus and the narrow range of outcomes explored. According to more
      recent systematic review evidence it is probable the shortcomings identified in
      the PICO review have not been addressed by subsequent research. The concept of
      model validity, proposed by other researchers, is discussed, and suggestions put
      forward about complex intervention evaluation methods, which may be better suited
      to evaluating acupuncture care. CONCLUSION: Uncertainty remains about the value
      of acupuncture care, as it is routinely practiced in the West, and this
      uncertainty has not been resolved by trials to date. Existing evaluations may
      however be useful for guiding decisions about the value of specific techniques
      for patients with depression.

PMID- 21091637
TI  - NAD+ depletion or PAR polymer formation: which plays the role of executioner in
      ischaemic cell death?
AB  - Multiple cell death pathways are activated in cerebral ischaemia. Much of the
      initial injury, especially in the core of the infarct where cerebral blood flow
      is severely reduced, is necrotic and secondary to severe energy failure. However,
      there is considerable evidence that delayed cell death continues for several
      days, primarily in the penumbral region. As reperfusion therapies grow in number
      and effectiveness, restoration of blood flow early after injury may lead to a
      shift towards apoptosis. It is important to elucidate what are the key mediators
      of apoptotic cell death after stroke, as inhibition of apoptosis may have
      therapeutic implications. There are two well described pathways that lead to
      apoptotic cell death; the caspase pathway and the more recently described caspase
      independent pathway triggered by poly-ADP-ribose polymers (PARP) activation.
      Caspase-induced cell death is initiated by release of mitochondrial cytochrome c,
      formation of the cytosolic apoptosome, and activation of endonucleases leading to
      a multitude of small randomly cleaved DNA fragments. In contrast caspase
      independent cell death is secondary to activation of apoptosis inducing factor
      (AIF). Mitochondrial AIF translocates to the nucleus, where it induces peripheral
      chromatin condensation, as well as characteristic high-molecular-weight (50 kbp)
      DNA fragmentation. Although caspase-independent cell death has been recognized
      for some time and is known to contribute to ischaemic injury, the upstream
      triggering events leading to activation of this pathway remain unclear. The two
      major theories are that ischaemia leads to nicotinamide adenine dinucleotide
      (NAD+) depletion and subsequent energy failure, or alternatively that cell death
      is directly triggered by a pro-apoptotic factor produced by activation of the DNA
      repair enzyme PARP. PARP activation is robust in the ischaemic brain producing
      variable lengths of poly-ADP-ribose (PAR) polymers as byproducts of PARP
      activation. PAR polymers may be directly toxic by triggering mitochondrial AIF
      release independently of NAD+ depletion. Recently, sex differences have been
      discovered that illustrate the importance of understanding these molecular
      pathways, especially as new therapeutics targeting apoptotic cell death are
      developed. Cell death in females proceeds primarily via caspase activation
      whereas caspase-independent mechanisms triggered by the activation of PARP
      predominate in the male brain. This review summarizes the current literature in
      an attempt to clarify the roles of NAD+ and PAR polymers in caspase-independent
      cell death, and discuss sex specific cell death to provide an example of the
      possible importance of these downstream mediators.

PMID- 21091640
TI  - Therapeutic role of 5-HT1A receptors in the treatment of schizophrenia and
      Parkinson's disease.
AB  - 5-HT(1A) receptors have long been implicated in the pathogenesis and treatment of
      anxiety and depressive disorders. Recently, several lines of studies have
      revealed new insights into the therapeutic role of 5-HT(1A) receptors in treating
      schizophrenia and Parkinson's disease. Specifically, 5-HT(1A) receptors seem to
      be a promising target for alleviating antipsychotic-induced extrapyramidal side
      effects (EPS) and cognitive/affective disorders in schizophrenia. In the
      treatment of patients with Parkinson's disease, 5-HT(1A) agonists are expected to
      improve not only affective symptoms (e.g., anxiety and depression), but also the
      core parkinsonian symptoms as well as antiparkinsonian agents-induced side
      effects (e.g., L-DOPA-induced dyskinesia). Here, the therapeutic mechanisms
      mediated by 5-HT(1A) receptors in schizophrenia and Parkinson's disease are
      reviewed. This evidence should encourage discovery of new 5-HT(1A) ligands, which
      can resolve the unmet clinical needs in the current therapy.

PMID- 21091641
TI  - Avian influenza survey in migrating waterfowl in Sonora, Mexico.
AB  - A two-year survey was carried out on the occurrence of avian influenza in
      migrating birds in two estuaries of the Mexican state of Sonora, which is located
      within the Pacific flyway. Cloacal and oropharyngeal swabs were collected from
      1262 birds, including 20 aquatic bird species from the Moroncarit and Tobari
      estuaries in Sonora, Mexico. Samples were tested for type A influenza (M), H5
      Eurasian and North American subtypes (H5EA and H5NA respectively) and the H7
      North American subtype (H7NA). Gene detection was determined by one-step real
      time reverse transcription polymerase chain reaction (RRT-PCR). The results
      revealed that neither the highly pathogenic avian influenza virus H5 of Eurasian
      lineage nor H7NA were detected. The overall prevalence of avian influenza type A
      (M-positive) in the sampled birds was 3.6% with the vast majority in dabbling
      ducks (Anas species). Samples from two birds, one from a Redhead (Aythya
      americana) and another from a Northern Shoveler (Anas clypeata), were positive
      for the low-pathogenic H5 avian influenza virus of North American lineage. These
      findings represented documented evidence of the occurrence of avian influenza in
      wintering birds in the Mexican wetlands. This type of study contributes to the
      understanding of how viruses spread to new regions of North America and
      highlights the importance of surveillance for the early detection and control of
      potentially pathogenic strains, which could affect animal and human health.

PMID- 21091642
TI  - Biomechanical properties and innervation of the female caveolin-1-deficient
      detrusor.
AB  - BACKGROUND AND PURPOSE: Caveolin-1-deficiency is associated with substantial
      urogenital alterations. Here, a mechanical, histological and biochemical
      characterization of female detrusors from wild-type and caveolin-1-deficient (KO)
      mice was made to increase the understanding of detrusor changes caused by lack of
      caveolae. EXPERIMENTAL APPROACH: Length-tension relationships were generated, and
      we recorded responses to electrical field stimulation, the muscarinic receptor
      agonist carbachol and the purinoceptor agonist ATP. Tyrosine nitration and the
      contents of caveolin-1, cavin-1, muscarinic M3 receptors, phospholipase C(beta1),
      muscle-specific kinase (MuSK) and L-type Ca(2+) channels were determined by
      immunoblotting. Innervation was assessed by immunohistochemistry. KEY RESULTS:
      Bladder to body weight ratio was not changed, nor was there any change in the
      optimum circumference for force development. Depolarization- and ATP-induced
      stress was reduced, as was carbachol-induced stress between 0.1 and 3 uM, but the
      supramaximal relative (% K(+)) response to carbachol was increased, as was M3
      expression. The scopolamine-sensitive component of the electrical field
      stimulation response was impaired, and yet bladder nerves contained little
      caveolin-1. The density of cholinergic nerves was unchanged, whereas CART- and
      CGRP-positive nerves were reduced. Immunoblotting revealed loss of MuSK.
      CONCLUSIONS AND IMPLICATIONS: Ablation of caveolae in the female detrusor leads
      to generalized impairment of contractility, ruling out prostate hypertrophy as a
      contributing factor. Cholinergic neuroeffector transmission is impaired without
      conspicuous changes in the density of cholinergic nerves or morphology of their
      terminals, but correlating with reduced expression of MuSK.

PMID- 21091643
TI  - Chronic Delta9-tetrahydrocannabinol treatment in rhesus monkeys: differential
      tolerance and cross-tolerance among cannabinoids.
AB  - BACKGROUND AND PURPOSE: The extent to which behavioural effects vary as a
      function of CB1 receptor agonist efficacy is not clear. These studies tested the
      hypothesis that cannabinoid tolerance and cross-tolerance depend upon the CB1
      agonist efficacy of drugs to which tolerance/cross-tolerance develops.
      EXPERIMENTAL APPROACH: Sensitivity to cannabinoids, including the cannabinoid
      antagonist rimonabant, low efficacy agonist Delta9-tetrahydrocannabinol (Delta9
      THC), and high efficacy agonists CP 55940 and WIN 55212-2, was determined before
      and after chronic Delta9-THC treatment in rhesus monkeys. Two measures of
      behavioural effect were assessed: effects of drugs to decrease fixed ratio
      responding for food presentation and stimulus-shock termination and
      discriminative stimulus effects in monkeys discriminating Delta9-THC (0.1 mg.kg
      1, i.v.). KEY RESULTS: Delta9-THC decreased responding for both food presentation
      and stimulus-shock termination; these effects were antagonized by the CB1
      antagonist rimonabant. Chronic Delta9-THC (1 mg.kg-1 per 12 h, s.c.) resulted in
      tolerance to the rate-decreasing effects of Delta9-THC and cross-tolerance to CP
      55940 and WIN 55212-2; however, cross-tolerance was less than tolerance. Chronic
      Delta9-THC increased sensitivity to rimonabant without changing sensitivity to
      the non-cannabinoids midazolam and ketamine. In monkeys discriminating Delta9-THC
      (0.1 mg.kg-1, i.v.), both CP 55940 and WIN 55212-2 produced high levels of drug
      lever responding. Chronic Delta9-THC (1 mg.kg-1 per day, s.c.) decreased
      sensitivity to Delta9-THC without producing cross-tolerance to CP 55940 or WIN
      55212-2. CONCLUSIONS AND IMPLICATIONS: In Delta9-THC-treated monkeys, the
      magnitude of tolerance and cross-tolerance to other CB1 receptor agonists varied
      inversely with agonist efficacy, suggesting that CB1 agonist efficacy is an
      important determinant of behavioural effects.

PMID- 21091644
TI  - Mechanisms for anti-inflammatory effects of 1-[15(S)-hydroxyeicosapentaenoyl]
      lysophosphatidylcholine, administered intraperitoneally, in zymosan A-induced
      peritonitis.
AB  - BACKGROUND AND PURPOSE: Lysophosphatidylcholines (lysoPCs) with polyunsaturated
      acyl chains are known to exert anti-inflammatory actions. 15-Lipoxygeanation is
      crucial for anti-inflammatory action of polyunsaturated acylated lysoPCs. Here,
      the anti-inflammatory actions of 1-(15-hydroxyeicosapentaenoyl)-lysoPC (15-HEPE
      lysoPC) and its derivatives were examined in a mechanistic analysis. EXPERIMENTAL
      APPROACH: Anti-inflammatory actions of 15-HEPE-lysoPC in zymosan A-induced
      peritonitis of mice were examined by measuring plasma leakage and leucocyte
      infiltration, and determining levels of lipid mediators or cytokines. KEY
      RESULTS: When each lysoPC, administered i.v., was assessed for its ability to
      suppress zymosan A-induced plasma leakage, 15-HEPE-lysoPC was found to be more
      potent than 1-(15-hydroperoxyeicosapentaenoyl)-lysoPC or 1-eicosapentaenoyl
      lysoPC. Separately, i.p. administration of 15-HEPE-lysoPC markedly inhibited
      plasma leakage, in contrast to 15-HEPE, which had only a small effect. 15-HEPE
      lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation
      of LTC4 and LTB4, 5-lipoxygenation products, as well as the levels of pro
      inflammatory cytokines. The time-course study indicated that 15-HEPE-lysoPC might
      participate in both the early inflammatory phase and resolution phase.
      Additionally, 15-HEPE-lysoPC administration caused a partial suppression of LTC4
      induced plasma leakage and LTB4-induced leucocyte infiltration. In the metabolism
      study, peritoneal exudate was shown to contain lysoPC-hydrolysing activity,
      crucial for anti-inflammatory activity, and a system capable of generating
      lipoxin A from 15-hydroxy eicosanoid precursor. CONCLUSIONS AND IMPLICATIONS: 15
      HEPE-lysoPC, a precursor for 15-HEPE in target cells, induced anti-inflammatory
      actions by inhibiting the formation of pro-inflammatory leukotrienes and
      cytokines, and by enhancing the formation of lipoxin A. 15-HEPE-lysoPC might be
      one of many potent anti-inflammatory lipids in vivo.

PMID- 21091646
TI  - Hydrogen sulphide protects mouse pancreatic beta-cells from cell death induced by
      oxidative stress, but not by endoplasmic reticulum stress.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide (H2S), a potentially toxic gas, is also
      involved in the neuroprotection, neuromodulation, cardioprotection,
      vasodilatation and the regulation of inflammatory response and insulin secretion.
      We have recently reported that H2S suppresses pancreatic beta-cell apoptosis
      induced by long-term exposure to high glucose. Here we examined the protective
      effects of sodium hydrosulphide (NaHS), an H2S donor, on various types of beta
      cell damage. EXPERIMENTAL APPROACH: Isolated islets from mice or the mouse
      insulinoma MIN6 cells were cultured with palmitate, cytokines (a mixture of
      tumour necrosis factor-alpha, interferon-gamma and interleukin-1beta), hydrogen
      peroxide, thapsigargin or tunicamycin with or without NaHS. We examined DNA
      fragmentation, caspase-3 and -7 activities and reactive oxygen species (ROS)
      production in the treated cells thereafter. Apoptotic cell death in isolated
      islets was also assessed by the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end labelling (TUNEL) method. KEY RESULTS: NaHS
      suppressed DNA fragmentation and the activities of caspase-3 and -7 induced by
      palmitate, the cytokines or hydrogen peroxide. In contrast, NaHS failed to
      protect islets and MIN6 cells from apoptosis induced by thapsigargin and
      tunicamycin, both of which cause endoplasmic reticulum stress. NaHS suppressed
      ROS production induced by cytokines or hydrogen peroxide but it had no effect on
      ROS production in thapsigargin-treated cells. NaHS increased Akt phosphorylation
      in MIN6 cells treated with cytokines but not in cells treated with thapsigargin.
      Treatment with NaHS decreased TUNEL-positive cells in cytokine-exposed islets.
      CONCLUSIONS AND IMPLICATIONS: H2S may prevent pancreatic beta-cells from cell
      apoptosis via an anti-oxidative mechanism and the activation of Akt signalling.

PMID- 21091645
TI  - Sphingosine-1-phosphate antibodies as potential agents in the treatment of cancer
      and age-related macular degeneration.
AB  - Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid thought to be
      dysregulated in a variety of disease conditions. In this review, we discuss the
      roles of S1P in cancer and in wet age-related macular degeneration. We also
      explore potential treatment strategies for these disorders, including the utility
      of anti-S1P antibodies acting as molecular sponges to neutralize dysregulated S1P
      in relevant tissues.

PMID- 21091647
TI  - Rescuing iron-overloaded macrophages by conservative relocation of the
      accumulated metal.
AB  - BACKGROUND AND PURPOSE: Systemic iron deficiency concomitant with macrophage iron
      retention is characteristic of iron-refractory anaemias associated with chronic
      disease. The systemic misdistribution of iron, which is further exacerbated by
      parenteral iron supplementation, is mainly attributable to iron retention exerted
      on resident macrophages by hepcidin-mediated down-regulation of the iron exporter
      ferroportin. We aimed at developing an experimental macrophage-based cell model
      that recapitulates pathophysiological features of iron misdistribution found in
      chronic disorders and use it as a screening platform for identifying agents with
      the potential for relocating the accumulated metal and restoring affected
      functions. EXPERIMENTAL APPROACH: A raw macrophage subline was selected as cell
      model of iron retention based on their capacity to take up polymeric iron or aged
      erythrocytes excessively, resulting in a demonstrable increase of cell labile
      iron pools and oxidative damage that are aggravated by hepcidin. KEY RESULTS:
      This model provided a three-stage high throughput screening platform for
      identifying agents with the combined ability to: (i) scavenge cell iron and
      thereby rescue macrophage cells damaged by iron-overload; (ii) bypass the
      ferroportin blockade by conveying the scavenged iron to other iron-starved cells
      in co-culture via transferrin but (iii) without promoting utilization of the
      scavenged iron by intracellular pathogens. As test agents we used chelators in
      clinical practice and found the oral chelator deferiprone fulfilled essentially
      all of the three criteria. CONCLUSIONS AND IMPLICATIONS: We provide a proof of
      principle for conservative iron relocation as complementary therapeutic approach
      for correcting the misdistribution of iron associated with chronic disease and
      exacerbated by parenteral iron supplementation.

PMID- 21091648
TI  - Functional antagonism of beta-adrenoceptor subtypes in the catecholamine-induced
      automatism in rat myocardium.
AB  - BACKGROUND AND PURPOSE: Myocardial automatism and arrhythmias may ensue during
      strong sympathetic stimulation. We sought to investigate the relevant types of
      adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the
      production of catecholaminergic automatism in atrial and ventricular rat
      myocardium. EXPERIMENTAL APPROACH: The effects of adrenoceptor agonists on the
      rate of spontaneous contractions (automatic response) and the amplitude of
      electrically evoked contractions (inotropic response) were determined in left
      atria and ventricular myocytes isolated from Wistar rats. KEY RESULTS:
      Catecholaminergic automatism was Ca(2+) -dependent, as it required a functional
      sarcoplasmic reticulum to be exhibited. Although both alpha- and beta
      adrenoceptor activation caused inotropic stimulation, only beta(1) -adrenoceptors
      seemed to mediate the induction of spontaneous activity. Catecholaminergic
      automatism was enhanced and suppressed by beta(2) -adrenoceptor blockade and
      stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and
      rolipram, respectively) potentiated the automatic response of myocytes to
      catecholamines. However, only rolipram abolished the attenuation of automatism
      produced by beta(2) -adrenoceptor stimulation. CONCLUSIONS AND IMPLICATIONS:
      alpha- and beta(2) -adrenoceptors do not seem to be involved in the mediation of
      catecholaminergic stimulation of spontaneous activity in atrial and ventricular
      myocardium. However, a functional antagonism of beta(1) - and beta(2) 
      adrenoceptor activation was identified, the former mediating catecholaminergic
      myocardial automatism and the latter attenuating this effect. Results suggest
      that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by
      beta(2) -adrenoceptor stimulation.

PMID- 21091649
TI  - Melatonin inhibits tachykinin NK2 receptor-triggered 5-HT release from guinea pig
      isolated colonic mucosa.
AB  - BACKGROUND AND PURPOSE: Melatonin is involved in the regulation of colonic
      motility, and sensation, but little is known about the influence of melatonin on
      5-hydroxytryptamine (5-HT) release from colonic mucosa. A tachykinin NK2 receptor
      selective agonist, [beta-Ala8]-neurokinin A(4-10) [betaAla-NKA-(4-10)] can induce
      5-HT release from guinea pig colonic mucosa via NK2 receptors on the mucosal
      layer. The present study was designed to determine the influence of melatonin on
      5-HT release from guinea pig colonic mucosa, evoked by the NK2 receptor agonist,
      betaAla-NKA-(4-10). EXPERIMENTAL APPROACH: The effect of melatonin was
      investigated on the outflow of 5-HT and its metabolite 5-hydroxyindoleacetic acid
      (5-HIAA) from muscle layer-free mucosal preparations of guinea pig colon, using
      high-performance liquid chromatography with electrochemical detection. KEY
      RESULTS: Melatonin caused a sustained decline in the betaAla-NKA-(4-10)-evoked 5
      HT outflow from the muscle layer-free mucosal preparations, but failed to affect
      its metabolite 5-HIAA outflow. The specific MT3 receptor agonist, 5
      methoxycarbonylamino-N-acetyltryptamine mimicked the inhibitory effect of
      melatonin on betaAla-NKA-(4-10)-evoked 5-HT outflow. A MT3 receptor antagonist
      prazosin shifted the concentration-response curve of melatonin to the right in a
      concentration-dependent manner and depressed the maximum effect, but neither a
      combined MT1/MT2 receptor antagonist luzindole, nor a MT2 receptor antagonist N
      pentanoyl-2-benzyltryptamine modified the concentration-response curve to
      melatonin. CONCLUSIONS AND IMPLICATIONS: Melatonin inhibits NK2 receptor
      triggered 5-HT release from guinea pig colonic mucosa by acting at a MT3
      melatonin receptor located directly on the mucosal layer, without affecting 5-HT
      degradation processes. Possible contributions of MT1/MT2 melatonin receptors to
      the inhibitory effect of melatonin appear to be negligible. Melatonin may act as
      a modulator of excess 5-HT release from colonic mucosa.

PMID- 21091651
TI  - Central nicotinic acetylcholine receptor involved in Ca(2+) -calmodulin
      endothelial nitric oxide synthase pathway modulated hypotensive effects.
AB  - BACKGROUND AND PURPOSE: Recent evidence has suggested that nicotine decreases
      blood pressure (BP) and heart rate (HR) in the nucleus tractus solitarii (NTS),
      indicating that nicotinic acetylcholine receptors (nAChRs) play an important role
      in BP control in the NTS. However, the signalling mechanisms involved in nAChR
      mediated depressor effects in the NTS are unclear. Hence, the aim of this study
      was to investigate these signalling mechanisms. EXPERIMENTAL APPROACH: Depressor
      responses to nicotine microinjected into the NTS of Wistar-Kyoto rats were
      elicited in the absence and presence of an antagonist of alpha7 nAChR, the
      calcium chelator ethylene glycol tetraacetic acid, a calmodulin-specific
      inhibitor, nitric oxide (NO) synthase (NOS) inhibitor, endothelial NOS (eNOS)
      selective inhibitor or neuronal NOS (nNOS)-specific inhibitor. KEY RESULTS:
      Microinjection of nicotine into the NTS produced a dose-dependent decrease in BP
      and HR, and increased nitrate levels. This depressor effect of nicotine was
      attenuated after pretreatment with a nAChR antagonist or blockers of the
      calmodulin-eNOS pathway. In contrast, N5-(1-Imino-3-butenyl)-L-ornithine (vinyl-L
      NIO), nNOS-specific inhibitor, did not diminish these nicotine-mediated effects.
      Calmodulin was found to bind eNOS after nicotine injection into NTS. However,
      nicotine did not affect the eNOS phosphorylation level or eNOS upstream
      extracellular signal-regulated kinases (ERK)1/2 and Akt phosphorylation levels.
      Furthermore, pretreatment with an ERK1/2 or Akt inhibitor did not attenuate
      nicotine-induced depressor effects in the NTS. CONCLUSIONS AND IMPLICATIONS:
      These results suggest that the nAChR-Ca(2+) -calmodulin-eNOS-NO signalling
      pathway, but not nNOS, plays a significant role in central BP regulation, and
      neither the ERK1/2 nor Akt signalling pathway are significantly involved in the
      activation of eNOS by nAChRs in the NTS.

PMID- 21091650
TI  - The glucocorticoid-induced TNF receptor family-related protein (GITR) is critical
      to the development of acute pancreatitis in mice.
AB  - BACKGROUND AND PURPOSE: Pancreatitis represents a life-threatening inflammatory
      condition where leucocytes, cytokines and vascular endothelium contribute to the
      development of the inflammatory disease. The glucocorticoid-induced tumour
      necrosis factor (TNF) receptor family-related protein (GITR) is a costimulatory
      molecule for T lymphocytes, modulates innate and adaptive immune system and has
      been found to participate in a variety of immune responses and inflammatory
      processes. Our purpose was to verify whether inhibition of GITR triggering
      results in a better outcome in experimental pancreatitis. EXPERIMENTAL APPROACH:
      In male GITR knock-out (GITR(-/-)) and GITR(+/+) mice on Sv129 background, acute
      pancreatitis was induced after i.p. administration of cerulein. Other
      experimental groups of GITR(+/+) mice were also treated with different doses of
      Fc-GITR fusion protein (up to 6.25 ug.mouse-1), given by implanted mini-osmotic
      pump. Clinical score and pro-inflammatory parameters were evaluated. KEY RESULTS:
      A less acute pancreatitis was found in GITR(-/-) mice than in GITR(+/+) mice,
      with marked differences in oedema, neutrophil infiltration, pancreatic
      dysfunction and injury. Co-treatment of GITR(+/+) mice with cerulein and Fc-GITR
      fusion protein (6.25 ug.mouse-1) decreased the inflammatory response and tissue
      injury, compared with treatment with cerulein alone. Inhibition of GITR
      triggering was found to modulate activation of nuclear factor kappaB as well as
      the production of TNF-alpha, interleukin-1beta, inducible nitric oxide synthase,
      nitrotyrosine, poly-ADP-ribose, intercellular adhesion molecule-1 and P-selectin.
      CONCLUSIONS AND IMPLICATIONS: The GITR-GITR ligand system is crucial to the
      development of acute pancreatitis in mice. Our results also suggest that the Fc
      GITR fusion protein could be useful in the treatment of acute pancreatitis.

PMID- 21091652
TI  - Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer
      cells reveals activation of the unfolded protein response (UPR).
AB  - BACKGROUND AND PURPOSE: Pancreatic cancer is one of the leading cancer-related
      causes of death due to high chemo-resistance and fast metastasation. Nemorosone,
      a polycyclic polyprenylated acylphloroglucinol, has recently been identified as a
      promising anticancer agent. Here, we examine its growth-inhibitory effects on
      pancreatic cancer cells. Based on transcription profiling, a molecular mode of
      action is proposed. EXPERIMENTAL APPROACH: Nemorosone cytotoxicity was assessed
      by the resazurin proliferation assay on pancreatic cancer cells and fibroblasts.
      Apoptosis was determined by Annexin V/propidium iodide staining as well as
      cytochrome c and caspase activation assays. Staining with the voltage-dependent
      dye JC-1 and fluorescence microscopy were used to detect effects on mitochondrial
      membrane potential. Total RNA was isolated from treated cell lines and subjected
      to microarray analysis, subsequent pathway identification and modelling. Gene
      expression data were validated by quantitative polymerase chain reaction and
      siRNA-mediated gene knock-down. KEY RESULTS: Nemorosone significantly inhibited
      cancer cell growth, induced cytochrome c release and subsequent caspase-dependent
      apoptosis, rapidly abolished mitochondrial membrane potential and elevated
      cytosolic calcium levels, while fibroblasts were largely unaffected. Expression
      profiling revealed 336 genes to be affected by nemorosone. A total of 75 genes
      were altered in all three cell lines, many of which were within the unfolded
      protein response (UPR) network. DNA damage inducible transcript 3 was identified
      as a key regulator in UPR-mediated cell death. CONCLUSIONS AND IMPLICATIONS:
      Nemorosone could be a lead compound for the development of novel anticancer drugs
      amplifying the already elevated UPR level in solid tumours, thus driving them
      into apoptosis. This study forms the basis for further investigations identifying
      nemorosone's direct molecular target(s).

PMID- 21091653
TI  - Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases
      survival rate of endotoxaemic mice.
AB  - BACKGROUND AND PURPOSE: Recently, metformin, a well-known anti-diabetic drug, has
      been shown to possess anti-inflammatory activities. This study investigated the
      effect of metformin on the expression of pro-inflammatory cytokines including
      high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-treated animals and
      cells. EXPERIMENTAL APPROACH: We investigated whether metformin inhibits the
      release of HMGB1 in LPS-treated RAW 264.7 cells and increases survival rate in
      endotoxaemic mice (lethal endotoxaemia was induced by an i.p. injection of LPS).
      This was achieved by a range of techniques including Western blotting, enzyme
      linked immunosorbent assay, specific pharmacological inhibitors, knock out of
      alpha(1) -subunit of AMP-activated protein kinase (AMPK) and recombinant HMGB1.
      KEY RESULTS: Both pre- and post-treatment with metformin significantly improved
      survival of animals during lethal endotoxaemia (survival rate was monitored up to
      2 weeks), decreased serum levels of tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1beta, HMGB1 expression and myeloperoxidase activity in lungs.
      However, metformin failed to improve survival in endotoxaemic animals that had
      additionally been treated with recombinant HMGB1. In an in vitro study, metformin
      dose-dependently inhibited production of pro-inflammatory cytokines and HMGB1
      release. Metformin activated AMPK by its phosphorylation. Compound C
      (pharmacological inhibitor of AMPK) and siAMPKalpha1 reversed the anti
      inflammatory effect of metformin in LPS-treated cells. CONCLUSIONS AND
      IMPLICATIONS: Our data indicate that metformin significantly attenuates the pro
      inflammatory response induced by LPS both in vivo and in vitro. Metformin
      improved survival in a mouse model of lethal endotoxaemia by inhibiting HMGB1
      release. AMPK activation was implicated as one of the mechanisms contributing to
      this inhibition of HMGB1 secretion.

PMID- 21091654
TI  - Principles of early drug discovery.
AB  - Developing a new drug from original idea to the launch of a finished product is a
      complex process which can take 12-15 years and cost in excess of $1 billion. The
      idea for a target can come from a variety of sources including academic and
      clinical research and from the commercial sector. It may take many years to build
      up a body of supporting evidence before selecting a target for a costly drug
      discovery programme. Once a target has been chosen, the pharmaceutical industry
      and more recently some academic centres have streamlined a number of early
      processes to identify molecules which possess suitable characteristics to make
      acceptable drugs. This review will look at key preclinical stages of the drug
      discovery process, from initial target identification and validation, through
      assay development, high throughput screening, hit identification, lead
      optimization and finally the selection of a candidate molecule for clinical
      development.

PMID- 21091655
TI  - Improving planning, design, reporting and scientific quality of animal
      experiments by using the Gold Standard Publication Checklist, in addition to the
      ARRIVE guidelines.
AB  - Several studies have demonstrated serious omissions in the way research that use
      animals is reported. In order to improve the quality of reporting of animal
      experiments, the Animals in research: reporting in vivo experiments (ARRIVE)
      Guidelines were published in the British Journal of Pharmacology in August 2010.
      However, not only the quality of reporting of completed animal studies needs to
      be improved, but also the design and execution of new experiments. With both
      these goals in mind, we published the Gold Standard Publication Checklist (GSPC)
      in May 2010, a few months before the ARRIVE guidelines appeared. In this letter,
      we compare the GSPC checklist with the ARRIVE Guidelines. The GSPC describes
      certain items in more detail, which makes it both easier to use when designing
      and conducting an experiment and particularly suitable for making systematic
      reviews of animal studies more feasible. In order to improve not only the
      reporting but also the planning, design, execution and thereby, the scientific
      quality of animal experiments, we strongly recommend to all scientists involved
      in animal experimentation and to editors of journals publishing animal studies to
      take a closer look at the contents of both the ARRIVE guidelines and GSPC, and
      select the set of guidelines which is most appropriate for their particular
      situation.

PMID- 21091656
TI  - Pregnane X receptor- and CYP3A4-humanized mouse models and their applications.
AB  - Pregnane X receptor (PXR) is a pivotal nuclear receptor modulating xenobiotic
      metabolism primarily through its regulation of CYP3A4, the most important enzyme
      involved in drug metabolism in humans. Due to the marked species differences in
      ligand recognition by PXR, PXR-humanized (hPXR) mice, and mice expressing human
      PXR and CYP3A4 (Tg3A4/hPXR) were established. hPXR and Tg3A4/hPXR mice are
      valuable models for investigating the role of PXR in xenobiotic metabolism and
      toxicity, in lipid, bile acid and steroid hormone homeostasis, and in the control
      of inflammation.

PMID- 21091657
TI  - How accurate is in vitro prediction of carcinogenicity?
AB  - Positive genetic toxicity data suggest carcinogenic hazard, and this can stop a
      candidate pharmaceutical reaching the clinic. However, during the last decade, it
      has become clear that many non-carcinogens produce misleading positive results in
      one or other of the regulatory genotoxicity assays. These doubtful conclusions
      cost a lot of time and money, as they trigger additional testing of apparently
      genotoxic candidates, both in vitro and in animals, to discover whether the
      suggested hazard is genuine. This in turn means that clinical trials can be put
      on hold. This review describes the current approaches to the 'misleading
      positive' problem as well as efforts to reduce the use of animals in genotoxicity
      assessment. The following issues are then addressed: the application of
      genotoxicity testing screens earlier in development; the search for new or
      improved in vitro genotoxicity tests; proposed changes to the International
      Committee on Harmonisation guidance on genotoxicity testing [S2(R1)]. Together,
      developments in all these areas offer good prospects of a more rapid and cost
      effective way to understand genetic toxicity concerns.

PMID- 21091658
TI  - Juvenile xanthogranuloma in monozygotic twins.
AB  - Juvenile xanthogranuloma is usually a benign condition mainly seen in infants and
      children. It frequently presents as asymptomatic discrete papules on the head,
      trunk, and limbs. Extracutaneous manifestations, most commonly ocular, are rare
      but may be associated with significant morbidity. The etiology of juvenile
      xanthogranuloma is uncertain, although the occurrence in monozygotic twins may
      suggest genetic predisposition.

PMID- 21091659
TI  - Speciation genetics of biological invasions with hybridization.
AB  - The negative effects of human-induced habitat disturbance and modification on
      multiple dimensions of biological diversity are well chronicled (Turner 1996;
      Harding et al. 1998; Lawton et al. 1998; Sakai et al. 2001). Among the more
      insidious consequences is secondary contact between formerly allopatric taxa
      (Anderson & Hubricht 1938; Perry et al. 2002; Seehausen 2006). How the secondary
      contact will play out is unpredictable (Ellstrand et al. 2010), but if the taxa
      are not fully reproductively isolated, hybridization is likely, and if the
      resulting progeny are fertile, the eventual outcome is often devastating from a
      conservation perspective (Rhymer & Simberloff 1996; Wolf et al. 2001; McDonald et
      al. 2008). In this issue of Molecular Ecology, Steeves et al. (2010) present an
      analysis of hybridization between two avian species, one of which is critically
      endangered and the other of which is invasive. Their discovery that the
      endangered species has not yet been hybridized to extinction is promising and not
      what one would necessarily expect from theory.

PMID- 21091660
TI  - Gene network architecture as a canvas for the interpretation of ecological
      genomics investigations.
AB  - New technologies promise to revolutionize the field of molecular ecology. This
      technological progress comes with its own set of challenges. Among the most
      important ones is the analysis and interpretation of the data in a way that tells
      us about the molecular causes of the phenotype of interest and its consequences.
      In this issue, Whitehead et al. (2010) reveal part of the mechanistic basis of
      evolved pollution tolerance by studying the developmental and transcriptional
      response of tolerant and sensitive fish embryos to polychlorinated biphenyls
      (PCBs), a pollutant commonly found in coastal waters of the United States. By
      integrating their gene expression profiling data with phenotypic data on
      individuals along with what is known about pathways by which this pollutant acts
      in zebrafish and mammals, they are able to suggest detailed mechanisms that have
      evolved to allow a fish population to adapt to a very damaging pollutant and
      develop normally.

PMID- 21091661
TI  - Frozen F1's amidst a masterpiece of nature: new insights into the rare hybrid
      origin of gynogenesis in the Amazon molly (Poecilia formosa).
AB  - All-female 'species' of fish have been shown to be great models in ecological and
      evolutionary studies because of the insights they can provide into the origin and
      evolution of asexuality, the ecology of hybrids, associations between genotype
      and environment, and the maintenance of sex. Gynogenetic organisms that evolved
      from sexual ancestors, and combine the disadvantageous traits from sexuality and
      asexuality, have long baffled evolutionary biologists trying to understand their
      origin and persistence with their sympatric sexual counterparts. In this issue, a
      new study using an integrated molecular phylogenetic and classical genetic
      approach has uncovered compelling evidence regarding the obscure asexual origin
      of the Amazon molly, Poecilia formosa. By performing an extensive phylogeographic
      analysis, Stock et al. (2010) provide evidence that the Amazon molly arose only
      once within its history, with monophyly being strongly supported by mitochondrial
      DNA and microsatellite analyses. This result, combined with an elaborate failed
      attempt to resynthesize the lineage, suggests that vertebrate gynogens such as
      the Amazon molly are not rare because they are at a disadvantage to their sexual
      counterparts, but because the genomic conditions under which they arise are rare.
      Organisms that apparently combine the disadvantages of both sexuality and
      asexuality remain difficult to understand from both an ecological and an
      evolutionary perspective, and Stock et al. (2010) highlight several outstanding
      important questions. Nonetheless, given that we now have a better knowledge of
      the origin and history of this unique 'species', this should allow researchers to
      better understand how these frozen F1's can persist amidst the masterpiece of
      nature.

PMID- 21091662
TI  - Evaluation of airway equipment: man or manikin?

PMID- 21091663
TI  - Reproducibility of non-standardised autonomic function testing in the pre
      operative assessment screening clinic*.
AB  - By convention, autonomic function tests are undertaken under standard test
      conditions that limit their implementation during routine pre-operative
      assessment. We therefore evaluated the comparability of autonomic function tests
      under both non-standardised and standardised test conditions in 20 healthy male
      subjects. Autonomic function was assessed using an ECG monitor and a continuous
      non-invasive blood pressure measurement device. Under non-standardised
      conditions, intraclass correlation for heart rate variability analysis was good
      for the low and high frequency bands (0.87; 95% CI 0.58-0.96 and 0.83; 95% CI
      0.56-0.94, respectively), but moderate (0.65; 95% CI 0.14-0.86) for the very low
      frequency band; reproducibility was high for the expiration/inspiration ratio
      (0.89; 95% CI 0.71-0.96), Valsalva ratio (0.76; 95% CI 0.37-0.91) and handgrip
      test (0.76; 95% CI 0.35-0.91) (all p<0.05) but was low for the response to quick
      standing. Reproducibility under standardised conditions was comparable to the
      above values. We demonstrated that reproducibility for most autonomic tests under
      non-standardised conditions is acceptable and suggest that implementation of
      these tests during pre-operative assessment may be feasible.

PMID- 21091664
TI  - A robust multifactor dimensionality reduction method for detecting gene-gene
      interactions with application to the genetic analysis of bladder cancer
      susceptibility.
AB  - A central goal of human genetics is to identify susceptibility genes for common
      human diseases. An important challenge is modelling gene-gene interaction or
      epistasis that can result in nonadditivity of genetic effects. The multifactor
      dimensionality reduction (MDR) method was developed as a machine learning
      alternative to parametric logistic regression for detecting interactions in the
      absence of significant marginal effects. The goal of MDR is to reduce the
      dimensionality inherent in modelling combinations of polymorphisms using a
      computational approach called constructive induction. Here, we propose a Robust
      Multifactor Dimensionality Reduction (RMDR) method that performs constructive
      induction using a Fisher's Exact Test rather than a predetermined threshold. The
      advantage of this approach is that only statistically significant genotype
      combinations are considered in the MDR analysis. We use simulation studies to
      demonstrate that this approach will increase the success rate of MDR when there
      are only a few genotype combinations that are significantly associated with case
      control status. We show that there is no loss of success rate when this is not
      the case. We then apply the RMDR method to the detection of gene-gene
      interactions in genotype data from a population-based study of bladder cancer in
      New Hampshire.

PMID- 21091665
TI  - Forkhead box P3+ T cells express interleukin-17 in nasal mucosa of patients with
      both allergic rhinitis and polyposis.
AB  - The pathogenesis of nasal polyposis remains unclear; it severely affects
      patients' quality of life and complicates inflammation in adjacent organs such as
      sinusitis and asthma. Aberrant immune regulatory function in these patients is
      proposed. The present study aims to examine the regulatory T cells (T(reg) ) in
      nasal mucosa of patients with allergic rhinitis (AR) and nasal polyposis (NP).
      Patients with AR or AR/NP were treated with inferior turbinectomy for their
      inferior turbinate hyperplasia. Surgically removed nasal mucosa was collected to
      examine the T(reg) by immunohistochemistry and flow cytometry. The results showed
      that more forkhead box P3 (FoxP3)(+) cells were found in AR with polyps than in
      those with AR alone. Further studies revealed that these FoxP3(+) T cells from
      AR/NP group also expressed interleukin (IL)-17. In vitro study showed that
      staphylococcal enterotoxin B (SEB) induced CD4(+) FoxP3(+) T cells to become
      FoxP3(+) IL-17(+) cells via facilitating the expression of IL-6, that in synergy
      with transforming growth factor-beta, induce the expression of IL-17 in FoxP3(+)
      cells. We conclude that FoxP3(+) IL-17(+) T cells were localized in the nasal
      mucosa of patients with AR and NP. SEB may play a role in converting FoxP3(+)
      T(reg) to FoxP3(+) IL-17(+) T cells. The presence of IL-17(+) FoxP3(+) T cells
      may play a role in the remodelling of the nasal airways in certain people who
      develop polyps, irrespective of whether or not they are atopic.

PMID- 21091666
TI  - Therapeutic failure in American cutaneous leishmaniasis is associated with
      gelatinase activity and cytokine expression.
AB  - Cutaneous lesions caused by Leishmania braziliensis infection occasionally heal
      spontaneously, but with antimonials therapy heal rapidly in approximately 3
      weeks. However, about 15% of the cases require several courses of therapy. Matrix
      metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that have been implicated
      in other chronic cutaneous diseases and skin re-epithelialization. These enzymes
      are controlled by their natural inhibitors [tissue inhibitors of
      metalloproteinase (TIMPs)] and by some cytokines. Uncontrolled gelatinase
      activity may result in intense tissue degradation and, consequently, poorly
      healing wounds. The present study correlates gelatinase activity to therapeutic
      failure of cutaneous leishmaniasis (CL) lesions. Our results demonstrate an
      association between gelatinase activity and increased numbers of cells making
      interferon (IFN)-gamma, interleukin (IL)-10 and transforming growth factor (TGF)
      beta in lesions from poor responders. Conversely, high levels of MMP-2 mRNA and
      enhanced MMP-2 : TIMP-2 ratios were associated with a satisfactory response to
      antimonials treatment. Additionally, high gelatinolytic activity was found in the
      wound beds, necrotic areas in the dermis and within some granulomatous
      infiltrates. These results indicate the importance of gelatinase activity in the
      skin lesions caused by CL. Thus, we hypothesize that the immune response profile
      may be responsible for the gelatinase activity pattern and may ultimately
      influence the persistence or cure of CL lesions.

PMID- 21091667
TI  - Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis.
AB  - Autoantibodies to intracellular targets in mitochondria and nuclei are
      serological hallmarks of primary biliary cirrhosis (PBC). One of the most
      recently identified cellular targets of PBC autoantibodies is a novel cytoplasmic
      structure referred to as GW bodies [GWB, G (glycine) W (tryptophan)-containing
      bodies (GWB)]. GWB are indentified as discrete cytoplasmic domains that are
      involved in mRNA processing via the RNA interference (RNAi) pathway. Key
      components of GWB include the proteins GW182, Ago2, RNA-associated protein 55
      (RAP55) and Ge-1/Hedls. The primary objective was to study the frequency and
      clinical association of antibodies directed to GWB components, in 109 PBC
      patients. Autoantibodies to mitochondrial antigen-pyruvate dehydrogenase complex
      (M2), branched-chain 2-oxo-acid dehydrogenase complex and 2-oxo glutarate
      dehydrogenase complex (3E-BPO), gp210, sp100, promyelocytic leukaemia cell
      antigen (PML) and liver kidney microsomal-1 antigen (LKM-1) were detected by a
      line immunoassay and antibodies to GWB (GW182, RAP55, Ge-1, GW2, GW3) and
      glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1), by
      an addressable laser bead immunoassay (ALBIA). The most common GWB autoantigen
      targets were: RAP55-28%, GW182-12%, GW2-2% and antibodies to GRASP-1-17%. By
      comparison, the frequency of reactivity to established PBC autoantigens was:
      gp210, 27%; sp100, 27% and PML, 17%. None of the autoantibodies were associated
      with differences in Mayo risk score or liver decompensation. This study is the
      first study to show that antibodies to RAP55, GW182 and GRASP-1 are the most
      common GWB targets in PBC.

PMID- 21091668
TI  - Toll-like receptor (TLR)-4 mediates anti-beta2GPI/beta2GPI-induced tissue factor
      expression in THP-1 cells.
AB  - Our previous study demonstrated that annexin A2 (ANX2) on cell surface could
      function as a mediator and stimulate tissue factor (TF) expression of monocytes
      by anti-beta2-glycoprotein I/beta2-glycoprotein I complex (anti
      beta2GPI/beta2GPI). However, ANX2 is not a transmembrane protein and lacks the
      intracellular signal transduction pathway. Growing evidence suggests that Toll
      like receptor 4 (TLR-4) might act as an 'adaptor' for intracellular signal
      transduction in anti-beta2GPI/beta2GPI-induced TF expressing cells. In the
      current study, we investigated the roles of TLR-4 and its related molecules,
      myeloid differentiation protein 2 (MD-2) and myeloid differentiation factor 88
      (MyD88), in anti-beta2GPI/beta2GPI-induced TF expressing human monocytic-derived
      THP-1 (human acute monocytic leukaemia) cells. The relationship of TLR-4 and ANX2
      in this process was also explored. Along with TF, expression of TLR-4, MD-2 and
      MyD88 in THP-1 cells increased significantly when treated by anti-beta2GPI (10
      ug/ml)/beta2GPI (100 ug/ml) complex. The addition of paclitaxel, which competes
      with the MD-2 ligand, could inhibit the effects of anti-beta2GPI/beta2GPI on TLR
      4, MD-2, MyD88 and TF expression. Both ANX2 and TLR-4 in THP-1 cell lysates could
      bind to beta2GPI that had been conjugated to a column (beta2GPI-Affi-Gel).
      Furthermore, TLR-4, MD-2, MyD88 and TF expression was remarkably diminished in
      THP-1 cells infected with ANX2-specific RNA interference (RNAi) lentivirus (LV
      RNAi-ANX2), in spite of treatment with a similar concentration of anti
      beta2GPI/beta2GPI complex. These results indicate that TLR-4 and its signal
      transduction pathway contribute to anti-beta2GPI/beta2GPI-induced TF expression
      in THP-1 cells, and the effects of TLR-4 with ANX2 are tightly co-operative.

PMID- 21091670
TI  - Multiple nodules on the trunk and arms.

PMID- 21091669
TI  - Prevention of excessive collagen accumulation by human intravenous immunoglobulin
      treatment in a murine model of bleomycin-induced scleroderma.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrotic
      changes in skin and other organs involving excessive collagen deposition. Here we
      investigated the effect of intravenous immunoglobulin (IVIG) on fibrosis in a
      murine model of bleomycin (BLM)-induced scleroderma. Scleroderma was induced in
      C3H/He J mice by subcutaneous BLM injections daily for 35 days. The collagen
      content in skin samples from the BLM-injected group (6.30 +/- 0.11 mg/g tissue)
      was significantly higher than the PBS group (5.80 +/- 0.10 mg/g tissue), and
      corresponded with dermal thickening at the injection site. In contrast, mice
      treated with IVIG for 5 consecutive days after initiating BLM injection showed
      lesser collagen content significantly (IVIG group, 5.61 +/- 0.09 mg/g tissue; BLM
      vs. IVIG). In order to investigate the cellular and protein characteristics in
      the early stage of the model, the skin samples were obtained 7 days after the
      onset of experiment. Macrophage infiltration to the dermis, monocyte
      chemoattractant protein (MCP-1)-positive cells, and increased TGF-beta1 mRNA
      expression were also observed in the BLM group. IVIG inhibited these early
      fibrogenic changes; MCP-1 expression was significantly lesser for the IVIG group
      (1.52 +/- 0.19 pg/mg tissue) than for the BLM group (2.49 +/- 0.26 pg/mg tissue).
      In contrast, TGF-beta1 mRNA expression was significantly inhibited by IVIG. These
      results suggest that IVIG treatment may inhibit macrophage recruitment to
      fibrotic sites by down regulating MCP-1 and TGF-beta production, and thus could
      be a potential drug for managing fibrotic disorders such as SSc.

PMID- 21091671
TI  - The role of drugs in the induction and/or exacerbation of psoriasis.
AB  - Psoriasis is a common skin disorder; knowledge of the factors that may induce,
      trigger, or exacerbate the disease is of primary importance in clinical practice.
      Drug intake is a major concern in this respect, as new drugs are constantly being
      added to the list of factors that may influence the course of this disease. Drug
      ingestion may result in exacerbation of pre-existing psoriasis, in induction of
      psoriatic lesions on clinically uninvolved skin in patients with psoriasis, or in
      precipitation of the disease in persons without family history of psoriasis or in
      predisposed individuals. In view of their relationship to drug-provoked
      psoriasis, therapeutic agents may be classified as drugs with strong evidence for
      a causal relationship to psoriasis, drugs about which there are considerable but
      insufficient data to support the induction or aggravation of the disease, and
      drugs that are occasionally reported to be associated with aggravation or
      induction. This review focuses on the most common causative agents for drug
      induced, drug-triggered, or drug-aggravated psoriasis, such as beta-blockers,
      lithium, synthetic antimalarial drugs, nonsteroidal anti-inflammatory agents, and
      tetracyclines, and the mechanisms of action of these drugs in the pathogenesis of
      psoriasis.

PMID- 21091672
TI  - A novel missense mutation in the ectodysplasin-A (EDA) gene underlies X-linked
      recessive nonsyndromic hypodontia.
AB  - BACKGROUND: Nonsyndromic hypodontia or congential absence of one or more
      permanent teeth is a common anomaly of dental development in humans. This
      condition may be inherited in an autosomal (dominant/recessive) or X-linked
      (dominant/recessive) mode. Mutations in three genes, PAX9, MSX1, and AXIN2, have
      been determined to be associated with autosomal dominant and recessive tooth
      agenesis. Recent studies in a few families showed that mutations in the
      ectodysplasin A (EDA) gene result in X-linked nonsyndromic hypodontia. METHODS:
      Genotyping of a five-generation Pakistani family with X-linked isolated
      hypodontia having three affected men was carried out using EDA-linked polymorphic
      microsatellite markers on chromosome Xq12-q13.1. To screen for a mutation in the
      EDA gene, all of its coding exons and splice junction sites were PCR amplified
      from genomic DNA of affected and unaffected individuals of the family and
      sequenced directly in an ABI Prism 310 automated DNA sequencer. RESULTS: We
      successfully mapped the affected locus to chromosome Xq12-q13.1, and found a
      novel missense mutation (c.993G>C) in the EDA gene in the affected men. The
      mutation causes substitution of glutamine with histidine (p.Q331H) in the tumor
      necrosis factor homology domain of EDA. CONCLUSIONS: A mutation identified in
      this study extends the body of evidence implicating the EDA gene in X-linked
      nonsyndromic hypodontia and supports the role of EDA-EDAR-EDARADD signaling in
      the morphogenesis of teeth.

PMID- 21091673
TI  - Japanese spotted fever with acute hepatic failure: was it associated with Epstein
      Barr virus?
AB  - BACKGROUND: An 81-year-old female experiencing high fever, fatigue, and loss of
      appetite was admitted to our hospital and diagnosed with acute cholecystitis. Her
      condition did not improve and an eschar and erythema subsequently appeared. We
      then diagnosed Japanese spotted fever (JSF). She recovered immediately after the
      administration of minocycline. This case differed from other cases because the
      patient had a remarkably acute hepatic failure. METHODS: Considering that the
      present case might be associated with other factors, we performed a repeat
      polymerase chain reaction (PCR) test on the patient's blood that had been
      collected on admission and stored. RESULTS: Epstein-Barr virus (EBV) was detected
      in her blood by PCR. CONCLUSION: We consider this case might be associated with
      EBV.

PMID- 21091674
TI  - HLA-DR6 association confers increased resistance to T. rubrum onychomycosis in
      Mexican Mestizos.
AB  - BACKGROUND: Onychomycosis is multifactorial in origin. Studies have suggested an
      autosomal dominant pattern of inheritance and human leukocyte antigen DR4 (HLA
      DR4) has been shown to protect against onychomycosis in an Ashkenazi Jewish
      population. AIM: This study investigates HLA class II association in a Mexican
      Mestizo population with Trichophyton rubrum onychomycosis. METHODS: This was a
      prospective case-control study. Mexican Mestizos with a clinical diagnosis of
      onychomycosis and culture positive for T. rubrum were recruited, together with
      age- and sex-matched controls. First-degree relatives were also investigated for
      onychomycosis. Case-control samples were HLA typed by polymerase chain reaction
      sequence-specific primer based analysis. RESULTS: Twenty-one cases and 42
      controls were recruited with a mean age of 40 years (range: 18-58 years). HLA-DR6
      was found in seven (33%) cases and 19 (45%) controls [P < 0.023, odds ratio (OR)
      = 0.088, 95% confidence interval (CI): 0.01-0.71]. Six (29%) cases and three (7%)
      controls had an affected child (P < 0.043, OR = 9.15, 95% CI: 1.07-78.31), and 13
      (62%) cases and 12 (29%) controls had an affected first-degree relative (P <
      0.02, OR = 4.0, 95% CI: 1.1-14.3). CONCLUSIONS: These results suggest that HLA
      DR6 confers protection against the development of onychomycosis in a Mexican
      Mestizo population. Having an affected first-degree relative significantly
      increases the risk of onychomycosis, suggesting genetic susceptibility.

PMID- 21091675
TI  - Cutaneous endometriosis.
AB  - A 32-year old patient presented with an asymptomatic, non-specific tumour located
      at the site of a previous cesarian scar. The tumor had never bled but its size
      changed and the color and consistency varied coinciding with the menstrual cycle.
      The dermatopathologic study showed the existence of ectopic endometrial glandular
      tissue in the whole thickness of the reticular dermis.

PMID- 21091676
TI  - Withdrawal of the culprit drug induces reactivation of human herpesvirus 6 in
      drug-induced hypersensitivity syndrome.

PMID- 21091677
TI  - A rare type of primary cutaneous amyloidosis: amyloidosis cutis dyschromica.

PMID- 21091678
TI  - Pancreatic panniculitis in a patient with BRCA2 mutation and metastatic
      pancreatic adenocarcinoma.

PMID- 21091679
TI  - It is not a fixed drug eruption, it is a fixed "sunlight" eruption.
AB  - Hyperpigmented fixed eruption is a phenomenon usually related with drug antigens,
      and known as fixed drug eruption. A woman had a skin condition with clinical and
      histopathologic indications of fixed drug eruption. The disease first appeared
      when she went to a swimming pool and left with hyperpigmented macules. Previously
      affected skin reactivated on three other occasions when she again visited
      swimming pools. Sunlight involvement (UVA-UVB) was demonstrated through
      phototests. Sunlight should be considered as a cause of fixed drug-like eruption
      and a possible cause of some cases of FDE without any apparent etiological
      factor.

PMID- 21091680
TI  - Oral submucosal fibrosis in Iran: a case review.

PMID- 21091681
TI  - Cutaneous spindle cell squamous cell carcinoma in nevus sebaceous.
AB  - A case of a 28 year-old Chinese male who presented with a rapidly growing tumor
      within a nevus sebaceous on his right cheek. The tumor was excised and
      immunohistochemical analysis and histology were consistent with spindle-cell
      squamous cell carcinoma. To the best of our knowledge, it is the first report of
      cutaneous spindle-cell squamous cell carcinoma developing in nevus sebaceous in
      the English literature. This report highlights the importance of early excision
      of any nevus sebaceous with a history of change.

PMID- 21091682
TI  - Clinical results of skin remodeling using a novel pneumatic technology.
AB  - BACKGROUND: A myriad of technologies are available for the treatment of aging
      skin. These, however, still lack the ability to combine immediate, short-term and
      long-term aesthetic results with no downtime. Furthermore, the treatment of fine
      wrinkles on large surfaces remains challenging, as does the treatment of delicate
      regions, such as the dorsal hand, neck, and chest. OBJECTIVES: The aims of this
      study were to evaluate the short-term as well as the long-term efficacy and
      safety of a new skin remodeling device that pneumatically accelerates a jet of
      hyaluronic acid (HA) solution under high pressure into the dermis. METHODS:
      Thirty-four participants at three clinical sites underwent treatments with the
      Airgent device on the face, neck, chest, and dorsal hands for a total of 69
      sites. Safety and efficacy were evaluated in short-term (1-3 months) and long
      term follow-up (up to 18 months) by photography, by an independent reviewer and
      by participant self-evaluation. Histology was assessed before and 4 months after
      the third treatment. RESULTS: A total of 69 treatment areas were evaluable at 1-3
      months follow-up. Photographic analysis demonstrated improvement in skin
      variables at all body sites treated. Treatment of the face and neck reduced the
      mean Fitzpatrick-Goldman Wrinkle Classification score by 39.4 and 30.4%,
      respectively, representing a full wrinkle class improvement. Treatments of the
      chest demonstrated significant visual improvement. Treatment of the dorsal hands
      produced good overall improvement (OI), with good improvement of protruding
      veins. Overall improvement increased with increasing number of treatments. A
      total of 56 treatment areas were evaluable for long-term follow-up. Treatment of
      the face and neck reduced the mean Fitzpatrick-Goldman Wrinkle Classification
      score by 27.6 and 21.2%, respectively. Improvement after treatment of the face
      represented a full wrinkle class reduction. Treatment of the chest and dorsal
      hands yielded significant visual improvement. Overall, 80% of subjects were
      satisfied with the treatment outcome and would recommend the treatment to friends
      and family. Histological analysis demonstrated increased dermal collagen
      IotaIotaIota. CONCLUSIONS: Pneumatic injection of HA under high pressure provides
      a safe, well-tolerated and effective method for improving the appearance of
      wrinkles on the face, neck, chest, and dorsal hands. Improvement can be seen as
      early as 1 month and as long as 18 months after treatment.

PMID- 21091683
TI  - Topical nadifloxacin 1% cream vs. topical erythromycin 4% gel in the treatment of
      mild to moderate acne.
AB  - Topical antibiotics are the mainstay of therapy in mild to moderate inflammatory
      acne. Topical erythromycin is one of the most common prescribed topical
      antibiotics. Nadifloxacin, another topical antibiotic for acne, was recently
      introduced into the market in our country. In this study, we compared the
      efficacies and safety of topical nadifloxacin 1% cream and erythromycin 4% gel in
      acne. A total of 86 patients with mild to moderate facial acne were randomized
      into two treatment groups. The efficacies of the drugs were assessed by lesion
      counts. An acne severity index (ASI) was also calculated. In both groups, there
      was a significant reduction in lesion counts and ASI scores beginning from the
      first visit at week 4. This reduction continued throughout the 12-week study
      period. Both treatments were well tolerated. We conclude that when topically
      applied, both nadifloxacin 1% cream and erythromycin 4% gel are equally effective
      and safe treatments for mild to moderate facial acne.

PMID- 21091684
TI  - Effective long-term control of refractory hidradenitis suppurativa with
      adalimumab after failure of conventional therapy.
AB  - BACKGROUND: Hidradenitis suppurativa is a chronic suppurative condition featuring
      inflammatory nodules, fistulas and scars. It occurs predominantly in the axillae
      and groin. The disease is poorly responsive to any treatment and is connected
      with significant morbidity. Systemic therapy, including oral antibiotics,
      retinoids and antiandrogens, usually has only limited effect. Surgical treatment
      of affected areas is necessary in advanced stages. OBJECTIVES: Several reports
      support the beneficial effect of tumor necrosis factor-alpha (TNF-alpha)
      antagonists for the treatment of severe hidradenitis suppurativa. By contrast
      with data on infliximab and etanercept, data describing the potential positive
      influence of adalimumab on disease outcome are limited and refer to only small
      cohorts of patients. METHODS: Eight patients with severe, recalcitrant
      hidradenitis were treated for 1 year with adalimumab in a standard regimen and
      were subsequently followed for 1 year. RESULTS: All patients improved within 4-6
      weeks and laboratory parameters of C-reactive protein (CRP) and leukocyte count
      reduced significantly during treatment. Three patients demonstrated long-lasting
      improvement and five showed recurrences several months after discontinuation of
      the therapy. The average recurrence-free interval was 9.5 months. CONCLUSIONS:
      Adalimumab is suitable for the long-term treatment of hidradenitis suppurativa
      and presents a further conservative treatment approach.

PMID- 21091685
TI  - Ritodrine-induced erythematous papular eruption in 14 pregnant women.
AB  - BACKGROUND: Ritodrine hydrochloride, a beta2-adrenergic agonist, has been used
      for the treatment of pre-term labor as a relatively safe agent, although
      tolerable side-effects have been occasionally reported. OBJECTIVE: The purpose of
      this study was to assess our clinical experience of skin eruptions caused by
      ritodrine. METHODS: Fourteen pregnant women with pruritic skin eruptions
      associated with the administration of ritodrine for pre-term labor were examined
      in Saitama Medical Center Hospital between 2005 and 2008. RESULTS: Patients
      included both primigravidas and multigravidas. Their mean age was 33.7 years
      (range: 27-41 years). Almost all subjects were in the third trimester of
      pregnancy. Skin eruptions occurred 7-27 days (mean: 14.9 days) after the start of
      intravenous or oral ritodrine. In eight patients, the eruption occurred after an
      increase in the dose of the drug. The reaction was characterized by a pruritic,
      erythematous, papular eruption, mainly distributed on the abdomen and upper
      extremities. Lymphocyte transformation tests for ritodrine were positive in five
      of the eight patients. CONCLUSIONS: Ritodrine-induced, erythematous, papular
      eruption probably occurs more frequently than has been previously estimated. An
      immunologic mechanism may play a role in the development of this eruption caused
      by ritodrine, although the reaction is somewhat dependent on the dose.

PMID- 21091686
TI  - Epidermal cyst infected by Entamoeba histolytica in a patient with no past
      history of intestinal amebiasis.

PMID- 21091687
TI  - Familial occurrence of calcifying epithelioma of Malherbe.

PMID- 21091688
TI  - Cutaneous sarcoidosis manifesting as extensive verrucous plaques.

PMID- 21091689
TI  - Linear lupus erythematosus profundus on the face, following the lines of
      Blaschko.

PMID- 21091690
TI  - A case of pustular vasculopathy. An atypical variant of Sweet's syndrome?

PMID- 21091691
TI  - Topical tacrolimus in the treatment of granuloma faciale.

PMID- 21091693
TI  - The impact of bone and suture material properties on mandibular function in
      Alligator mississippiensis: testing theoretical phenotypes with finite element
      analysis.
AB  - The functional effects of bone and suture stiffness were considered here using
      finite element models representing three different theoretical phenotypes of an
      Alligator mississippiensis mandible. The models were loaded using force estimates
      derived from muscle architecture in dissected specimens, constrained at the 18th
      and 19th teeth in the upper jaw and 19th tooth of the lower jaw, as well as at
      the quadrate-articular joint. Stiffness was varied systematically in each
      theoretical phenotype. The three theoretical phenotypes included: (i) linear
      elastic isotropic bone of varying stiffness and no sutures; (ii) linear elastic
      orthotropic bone of varying stiffness with no sutures; and (iii) linear elastic
      isotropic bone of a constant stiffness with varying suture stiffness. Variation
      in the isotropic material properties of bone primarily resulted in changes in the
      magnitude of principal strain. By comparison, variation in the orthotropic
      material properties of bone and isotropic material properties of sutures resulted
      in: a greater number of bricks becoming either more compressive or more tensile,
      changing between being either dominantly compressive or tensile, and having
      larger changes in the orientation of maximum principal strain. These data
      indicate that variation in these model properties resulted in changes to the
      strain regime of the model, highlighting the importance of using biologically
      verified material properties when modeling vertebrate bones. When bones were
      compared within each set, the response of each to changing material properties
      varied. In two of the 12 bones in the mandible, varied material properties within
      sutures resulted in a decrease in the magnitude of principal strain in bricks
      adjacent to the bone/suture interface and decreases in stored elastic energy. The
      varied response of the mandibular bones to changes in suture stiffness highlights
      the importance of defining the appropriate functional unit when addressing
      relationships of performance and morphology.

PMID- 21091694
TI  - Identification of genes expressed in maize root cortical cells during lysigenous
      aerenchyma formation using laser microdissection and microarray analyses.
AB  - * To adapt to waterlogging in soil, some gramineous plants, such as maize (Zea
      mays), form lysigenous aerenchyma in the root cortex. Ethylene, which is
      accumulated during waterlogging, promotes aerenchyma formation. However, the
      molecular mechanism of aerenchyma formation is not understood. * The aim of this
      study was to identify aerenchyma formation-associated genes expressed in maize
      roots as a basis for understanding the molecular mechanism of aerenchyma
      formation. Maize plants were grown under waterlogged conditions, with or without
      pretreatment with an ethylene perception inhibitor 1-methylcyclopropene (1-MCP),
      or under aerobic conditions. Cortical cells were isolated by laser
      microdissection and their mRNA levels were examined with a microarray. * The
      microarray analysis revealed 575 genes in the cortical cells, whose expression
      was either up-regulated or down-regulated under waterlogged conditions and whose
      induction or repression was suppressed by pretreatment with 1-MCP. * The
      differentially expressed genes included genes related to the generation or
      scavenging of reactive oxygen species, Ca(2+) signaling, and cell wall loosening
      and degradation. The results of this study should lead to a better understanding
      of the mechanism of root lysigenous aerenchyma formation.

PMID- 21091695
TI  - Regulation of the molecular response to oxygen limitations in plants.
AB  - The oxygen availability to plant tissues can vary strongly in time and space. To
      endure short- or long-term oxygen deprivation, plants evolved a series of
      metabolic and morphological adaptations that have been extensively studied.
      However, our knowledge of the molecular regulation of these processes is not as
      well understood. In this review, the recent findings on the molecular effectors
      that regulate the response of higher plants to oxygen deficiency are discussed.
      Although no direct oxygen sensor has been discovered in plants so far, mechanisms
      that perceive low-oxygen derived signals have been reported, involving different
      sets of transcription factors (TFs). The ERF (Ethylene Responsive Factor) family
      especially appears to play a crucial role in the determination of survival to
      reduced oxygen availability in Arabidopsis and rice. This class of TFs displays a
      broad range of targets, being involved in both the metabolic reprogramming and
      the morphological adaptations exploited by plants when subjected to low-oxygen
      conditions.

PMID- 21091696
TI  - Genetic evidence for auxin involvement in arbuscular mycorrhiza initiation.
AB  - * Formation of arbuscular mycorrhiza (AM) is controlled by a host of small,
      diffusible signaling molecules, including phytohormones. To test the hypothesis
      that the plant hormone auxin controls mycorrhiza development, we assessed
      mycorrhiza formation in two mutants of tomato (Solanum lycopersicum):
      diageotropica (dgt), an auxin-resistant mutant, and polycotyledon (pct), a mutant
      with hyperactive polar auxin transport. * Mutant and wild-type (WT) roots were
      inoculated with spores of the AM fungus Glomus intraradices. Presymbiotic root
      fungus interactions were observed in root organ culture (ROC) and internal fungal
      colonization was quantified both in ROC and in intact seedlings. * In ROC, G.
      intraradices stimulated presymbiotic root branching in pct but not in dgt roots.
      pct roots stimulated production of hyphal fans indicative of appressorium
      formation and were colonized more rapidly than WT roots. By contrast, approaching
      hyphae reversed direction to grow away from cultured dgt roots and failed to
      colonize them. In intact seedlings, pct and dgt roots were colonized poorly, but
      development of hyphae, arbuscules, and vesicles was morphologically normal within
      roots of both mutants. * We conclude that auxin signaling within host roots is
      required for the early stages of AM formation, including during presymbiotic
      signal exchange.

PMID- 21091697
TI  - A pilot iron substitution programme in female blood donors with iron deficiency
      without anaemia.
AB  - BACKGROUND AND OBJECTIVES: Blood donation can contribute to iron deficiency. The
      possibly resulting anaemia importantly affects donor return rate. The
      determination of serum ferritin levels revealed iron deficiency in many non
      anaemic premenopausal female blood donors at our Institution. We started an iron
      substitution programme targeting this donor group to prevent anaemia and enhance
      donor retain. MATERIALS AND METHODS: Women aged<=50 with haemoglobin levels
      adequate for donation and serum ferritin<=10 ng/ml were offered iron
      supplementation. Substitution lasted 16 weeks and the donation interval was
      extended. History collection including iron deficiency-related symptoms, whole
      blood count and serum ferritin determination was performed at baseline and after
      2 and 6 months. Data were recorded prospectively and compared with those of 108
      female controls with iron deficiency not receiving iron substitution
      (retrospective data). RESULTS: Of the 116 participating subjects, 60% completed
      the programme. Significant results were serum ferritin increase (from a mean
      value of 7.12 to 25.2 ng/ml), resolution of prostration, fatigue, sleep
      disturbances, tension in the neck, hair loss and nail breakage. No case of
      anaemia occurred. Sixty per cent of the women completed the programme and donated
      blood again. CONCLUSIONS: Targeted iron substitution prevents the development of
      anaemia and enhances donation return in premenopausal female blood donors with
      iron deficiency.

PMID- 21091698
TI  - Processing cord blood from premature infants into autologous red-blood-cell
      products for transfusion.
AB  - BACKGROUND AND OBJECTIVES: The use of umbilical cord blood (UCB) for transfusion
      purposes has gained interest the past years. UCB transfusion could serve
      premature infants, who often need transfusions early in life. MATERIAL AND
      METHODS: We investigated the suitability of different storage media. UCB was
      collected after 25 0/7--35 6/7 gestational weeks and centrifuged to concentrate
      red cells subsequently stored in saline-adenine-glucose-mannitol (SAGM), or in
      additive solution-3 (AS-3), or stored as whole blood in citrate-phosphate
      dextrose-adenine-1. Quality parameters were measured at 7 day intervals during 35
      days and compared to the standard RBC product. RESULTS: White-blood-cell- and
      platelet counts were higher in the UCB products. In the fractionated units,
      haemolysis remained below 1.0% in 64% after 14 days, and in 30% after 21 days.
      Storage in SAGM or AS-3 showed similar quality. Whole blood UCB showed better pH
      and haemolysis rates after 21 days. CONCLUSION: UCB can be processed into
      autologous products for premature infants. Shelf-life is limited to 14-21 days
      and compares unfavourably to stored whole blood. Considering the early
      transfusion needs in these infants, a short shelf-life would not be a practical
      objection.

PMID- 21091699
TI  - Facilitating access to evidence--a benefit to the profession.

PMID- 21091700
TI  - Community occupational therapists' clinical reasoning: identifying tacit
      knowledge.
AB  - BACKGROUND:   Occupational therapy interventions in the community, a fast
      expanding practice setting, are central to an important social priority, the
      ability to live at home. These interventions generally involve only a small
      number of home visits, which aim at maximising the safety and autonomy of
      community-dwelling clients. Knowing how community occupational therapists
      determine their interventions, i.e. their clinical reasoning, can improve
      intervention efficacy. However, occupational therapists are often uninformed
      about and neglect the importance of clinical reasoning, which could underoptimise
      their interventions. AIM:   To synthesise current knowledge about community
      occupational therapists' clinical reasoning. METHOD:   A scoping study of the
      literature on community occupational therapists' clinical reasoning was
      undertaken. RESULTS:   Fifteen textbooks and 25 articles, including six focussing
      on community occupational therapists' clinical reasoning, were reviewed.
      Community occupational therapists' clinical reasoning is influenced by internal
      and external factors. Internal factors include past experiences, expertise and
      perceived complexity of a problem. One of the external factors, practice context
      (e.g. organisational or cultural imperatives, physical location of intervention),
      particularly shapes community occupational therapists' clinical reasoning, which
      is interactive, complex and multidimensional. However, the exact influence of
      many factors (personal context, organisational and legal aspects of health care,
      lack of resources and increased number of referrals) remains unclear. CONCLUSION:
      Further studies are needed to understand better the influence of internal and
      external factors. The extent to which these factors mould the way community
      occupational therapists think and act could have a direct influence on the
      services they provide to their clients.

PMID- 21091701
TI  - Sensory processing and stereotypical and repetitive behaviour in children with
      autism and intellectual disability.
AB  - BACKGROUND: Sensory processing disorders have been linked to stereotypical
      behaviours in children with intellectual disability (ID) and autism spectrum
      disorders (ASD) and to anxiety in children with ASD. In earlier phases of this
      study with the same participants, we found that those with both ASD and ID were
      more motivated than those with ID alone to engage in stereotypical behaviour to
      alleviate anxiety. In this phase, we confirmed that children with both ASD and ID
      and those with ID alone process sensation differently than typically developing
      children. We asked: Do the sensory processing difficulties of children with ASD
      and ID differ significantly from those of children with ID alone in a way that
      would help explain the increased anxiety of the former group? METHOD: Parents of
      children with ASD and ID (n = 29; mean age 9.7 years) and with ID alone (n = 23;
      mean age 9.5 years) completed a Sensory Profile (SP) to provide information about
      their children's sensory processing abilities. SP quadrant scores for each group
      were compared with each other and with the published norms of typically
      developing children. RESULTS:   Children with ASD and ID and with ID alone
      processed sensory information differently than typically developing children
      (P=0.0001;d= >2.00). Children with both ASD and ID were significantly more
      sensitive (P=0.007;d=0.70) and avoidant (P < 0.05;d=0.47) than the children with
      ID alone. CONCLUSION: We conclude that increased sensitivity and the tendency to
      avoid sensation may help explain anxiety in children with autism.

PMID- 21091702
TI  - Translating knowledge to practice: an occupational therapy perspective.
AB  - BACKGROUND/AIM: Translating knowledge to practice, also called 'knowledge
      translation', is increasingly recognised as a driving force to strengthen and
      improve the healthcare system. How knowledge translation fits with occupational
      therapy practice deserves examination. METHODS: This paper will explore how an
      action process model, the Knowledge-To-Action Process, may advance knowledge
      translation in occupational therapy. Occupational therapists typically view
      knowledge in a broad sense, encompassing research, tacit knowledge, expert
      opinion and client evidence. The Knowledge-To-Action Process facilitates
      application of client, therapist and research knowledge to occupational therapy
      practice. RESULTS: Examination of knowledge translation through the lens of the
      Knowledge-To-Action Process creates awareness of the value of client, therapist
      and research knowledge. It also highlights opportunities as practitioners to
      implement knowledge translation. CONCLUSIONS: Models able to flexibly reflect an
      occupational therapy perspective of knowledge have a potentially vital role in
      successful knowledge translation. Furthermore, these models allow therapists and
      other stakeholders to analyse complex situations and identify targeted knowledge
      translation strategies.

PMID- 21091703
TI  - Continuing professional development for occupational therapy emergency department
      services.
AB  - AIM: To explore continuing professional development (CPD) resources and needs of
      Australian emergency department occupational therapists. METHOD: Australian
      websites and occupational therapy newsletters were searched to identify CPD
      resources/opportunities. Occupational therapists with recent clinical experience
      in Australian emergency departments were surveyed on strengths, weaknesses,
      opportunities and threats to their service, research information needs,
      supervision/mentor arrangements and quality assurance activity. RESULTS: No
      Australian CPD opportunities were identified; 1.3% of the 2008 OT AUSTRALIA
      conference topics were emergency department specific. Forty-one Australian
      hospitals employed a total of 51 occupational therapists of whom 30 responded.
      Half were supervised by occupational therapists; 20 had occupational therapy
      mentors; 23 perceived that they were very independent; seven did quality
      assurance projects; 25 had unmet research needs; 27 thought their service was
      effective; and service strengths, weaknesses, opportunities and threats to
      service could be identified by most occupational therapists. CONCLUSION:
      Australian occupational therapists in emergency departments need specialised CPD
      opportunities. The information needs and strengths, weaknesses, opportunities and
      threats provide a CPD topic planning guide.

PMID- 21091704
TI  - The effect of education with workplace supports on practitioners' evidence-based
      practice knowledge and implementation behaviours.
AB  - BACKGROUND/AIM: Individual and workplace barriers affect uptake of evidence-based
      practice (EBP). This study evaluated the effects of a 1-day workshop with
      workplace supports on allied health professionals' EBP knowledge and behaviour.
      METHODS: A prospective longitudinal pre-post design was used. A total of 88
      allied health professionals participated. Knowledge was measured using the
      Adapted Fresno Test (AFT), behaviour was measured using frequency counts of
      presentations using EBP methodologies and critically appraised topics (CATs) were
      produced. Mean differences were analysed using paired t-tests. RESULTS: EBP
      knowledge significantly improved immediately after education on the AFT (from
      36.67 to 46.84/156) a mean change of 10.17 points (95% confidence interval (CI):
      7.19-13.50) (P <0.001). Behaviour also changed over 18 months. EBP content in
      presentations increased from 3 to 100% (t = 24.39, P <0.001, 95%CI: 0.86-1.03).
      CATs produced significantly increased by 0.26 per head (t =5.55, P <0.001, 95%
      CI: 0.17-0.35). CONCLUSIONS: Education with workplace supports (supervision,
      incentives, resource allocation and working groups) may lead to improvements in
      EBP knowledge and implementation.

PMID- 21091705
TI  - Novice occupational therapists' perceptions of readiness to undertake fieldwork
      supervision.
AB  - AIM: This study investigated new graduate occupational therapists' perceived
      readiness for the fieldwork supervisor role at a metropolitan Melbourne Hospital.
      METHODS: Data from four in-depth individual interviews and a focus group
      conducted with seven Grade 1 occupational therapists were analysed thematically.
      An iterative process was used to develop themes from the categories of data.
      RESULTS: The new graduate occupational therapists' perceived readiness for
      supervising students was strongly influenced by a sense of still learning
      themselves. High expectations were expressed of the supervisory role. Active
      support and supervision from the workplace and the university are seen as
      necessary. CONCLUSIONS: A deeper understanding of the supervisory role and
      associated skills required for new graduate therapists is needed. Support from
      senior colleagues and workshops conducted by the university to up-skill the
      therapists are recommended.

PMID- 21091706
TI  - Online discussions develop students' clinical reasoning skills during fieldwork.
AB  - AIM: Pilot study to examine if the addition of a structured framework improved
      the quality of clinical reasoning demonstrated within clinically based online
      discussions by occupational therapy students undertaking fieldwork. METHODS:
      Cognitive elements of the clinical reasoning process present within students'
      discussions were compared before (2005 cohort) and after (2007 cohort) the
      introduction of a structured framework to guide discussions. Students' self
      reports (2007 cohort) of clinical reasoning skills were also analysed before and
      after two consecutive fieldwork placements. RESULTS: The structured framework
      increased the proportion of postings containing the advanced 'evaluate' element
      of clinical reasoning and decreased the proportion of postings containing only
      the basic 'understand' elements. Self-reported clinical reasoning skills improved
      following the first fieldwork placement and this improvement was sustained
      following the second placement. CONCLUSIONS: The structured framework appears
      useful in enhancing students' depth of clinical reasoning during fieldwork,
      although further investigation is required.

PMID- 21091707
TI  - A case against generalisation of mental health occupational therapy in Australia.
AB  - BACKGROUND/AIM: In 2009, the World Federation of Occupational Therapists
      International Advisory Group on Mental Health conducted a global survey that
      yielded data on mental health occupational therapy practice. The Australian
      dataset reflected aspects of the current situation of the Australian mental
      health occupational therapy workforce. Of particular interest were resource
      availability, workforce recruitment and retention, and perception of the future
      of mental health occupational therapy. METHODOLOGY: Using a cross-sectional
      survey design, quantitative and qualitative data were gathered electronically
      over a one-month period. Manual analysis indicated themes common to mental health
      occupational therapists across a framework of professional areas. RESULTS:
      Findings suggested that role blurring negatively affected workforce retention.
      Workforce recruitment and retention were complicated by resource shortages. Some
      Federal Government initiatives were perceived as only partially beneficial to the
      profession. CONCLUSIONS: Survey respondents believed that mental health
      occupational therapy was a potential growth area particularly where occupational
      therapy specific skills were retained.

PMID- 21091708
TI  - Occupational therapists' self-insight into their referral prioritisation policies
      for clients with mental health needs.
AB  - BACKGROUND/AIM: Obtaining valid accounts of professionals' thinking is dependent
      upon experts' capacity for self-insight. Self-insight has implications for
      developing professional decision making, facilitating education and promoting
      agreement among therapists. The aim of this study was to examine occupational
      therapists' self-insight into their referral prioritisation policies. METHODS: A
      total of 40 occupational therapists individually rated the importance that
      differing types of referral content had on their prioritisation of referrals.
      These subjective policies were then correlated with their objective referral
      prioritisation policies that had been previously statistically derived. RESULTS:
      Self-insight was found to be moderate but with wide variation across individuals
      and across referral information used. Self-insight on cues that were important to
      the decision was found to be better than on those cues not so important to the
      decision. CONCLUSIONS:   Occupational therapists have similar levels of self
      insight to other professional groups. The 'attention hypothesis' may explain why
      self-insight varied across referral information used.

PMID- 21091709
TI  - Refugee settlement workers' perspectives on home safety issues for people from
      refugee backgrounds.
AB  - BACKGROUND/AIM: Refugees experience higher levels of emotional, psychological and
      physical distress than the general migrant population during settlement in a new
      country. Safety in the home can be a major concern and is an issue of which
      occupational therapists should be aware. Occupational therapists working with
      refugees in many contexts feel unprepared and overwhelmed. As refugee settlement
      workers attend to home safety of refugees during the settlement process, this
      study aimed to develop an in-depth understanding of their perceptions of this
      issue. Such information can contribute to occupational therapists' knowledge and
      practice when working with refugees. METHODS: An exploratory qualitative case
      study approach used 16 semi-structured interviews and observation of a settlement
      worker assisting newly arrived refugees. Participants were settlement service
      staff (an occupational therapist, case coordinators and cultural support
      workers). RESULTS: Three themes are reported: considerations for safety in the
      homes of refugees; factors influencing home safety for refugees; and sensitivity
      to culture. Participants described tailoring home safety-related services to each
      individual based on factors that influence home safety and sensitivity to
      culture. CONCLUSION: Awareness of home safety issues can increase cultural
      competence and inform practice and policy.

PMID- 21091710
TI  - The test-retest reliability and responsiveness to change for the Hand Function
      Survey during stroke rehabilitation.
AB  - BACKGROUND/AIM: The Hand Function Survey (HFS) is a questionnaire designed to
      measure self-reported ability to use the affected hand during 13 everyday tasks
      in people with stroke. The HFS appears practical for clinical use and has
      established psychometric properties. This study aimed to investigate test-retest
      reliability and responsiveness to change for the HFS during stroke
      rehabilitation. METHODS: Twenty-two people with a first episode stroke, and
      without severe cognitive and language difficulties, participated. Participants
      were assessed on three occasions: baseline, 48 hours later and at follow-up (four
      to six weeks later) using two tests of upper extremity function, the HFS and the
      Action Research Arm Test (ARAT). Test-retest reliability of the HFS between
      baseline and 48 hours was examined using tests of agreement (Lin's Concordance
      and Cohen's Kappa). Responsive to change for the HFS was investigated by
      comparing the difference between baseline and follow-up scores. The level of
      agreement between the change observed for the ARAT and HFS was analysed. RESULTS:
      Strong agreement (Rho_c = 0.99; Kappa(w) =0.97) was observed between the test
      retest HFS scores. Significant improvement between baseline and follow-up
      occurred for both the HFS and ARAT. A moderate agreement was found between change
      observed for the HFS and ARAT (Rho_c=0.62; Kappa(w) =0.65). CONCLUSION: The HFS
      was found to be a reliable and responsive self-report test of hand function
      during stroke rehabilitation. The HFS could be used in conjunction with other
      clinical tests of hand function during the rehabilitation of people with stroke
      without severe cognitive and language difficulties.

PMID- 21091711
TI  - Workplace interventions did not improve health, but reduced sickness absence
      among workers with musculoskeletal disorders.

PMID- 21091712
TI  - Eight weeks of occupational therapy home programme, compared to no programme,
      resulted in improved achievement of child and family-selected goals by children
      with cerebral palsy.

PMID- 21091713
TI  - Cardiovascular outcomes in type 2 diabetes: the impact of preventative therapies.
AB  - The world is facing an unprecedented increase in type 2 diabetes. Most disability
      and premature mortality experienced by people with diabetes is related to
      cardiovascular disease. This review summarizes recent evidence about approaches
      for managing cardiovascular risk in patients with type 2 diabetes. While optimal
      blood pressure targets in people with diabetes remain uncertain, new data have
      demonstrated the benefits of routine blood pressure lowering in these patients,
      when administered without regard to initial blood pressure level. Other recent
      data indicate that blood pressure lowering treatment in patients with diabetes
      needs to be continued for ongoing benefit. The effects of intensive blood glucose
      lowering have been evaluated recently in a number of large trials, and
      individually these have failed to provide evidence of cardioprotection over a 4-5
      year period. However, longer-term follow-up data suggest that there may be a
      delay in any such benefits becoming apparent. The benefits of statin therapy in
      preventing cardiovascular events in diabetic patients have been recently
      confirmed in a systematic overview of relevant trials; however, effects of
      fibrate therapy appear more limited. The role of antiplatelet agents remains
      unknown, as adequately powered trials of aspirin for the primary prevention of
      cardiovascular events in patients with diabetes have not yet been completed.

PMID- 21091714
TI  - The genetics of type 2 diabetes: what have we learned from GWAS?
AB  - Type 2 diabetes mellitus has been at the forefront of human diseases and
      phenotypes studied by new genetic analyses. Thanks to genome-wide association
      studies, we have made substantial progress in elucidating the genetic basis of
      type 2 diabetes. This review summarizes the concept, history, and recent
      discoveries produced by genome-wide association studies for type 2 diabetes and
      glycemic traits, with a focus on the key notions we have gleaned from these
      efforts. Genome-wide association findings have illustrated novel pathways,
      pointed toward fundamental biology, confirmed prior epidemiological observations,
      drawn attention to the role of beta-cell dysfunction in type 2 diabetes,
      explained ~10% of disease heritability, tempered our expectations with regard to
      their use in clinical prediction, and provided possible targets for
      pharmacotherapy and pharmacogenetic clinical trials. We can apply these lessons
      to future investigation so as to improve our understanding of the genetic basis
      of type 2 diabetes.

PMID- 21091715
TI  - The role of SAP and SLAM family molecules in the humoral immune response.
AB  - Effective B cell-mediated immunity, including the formation of germinal centers
      and the generation of high-affinity memory B cells and long-lived plasma cells,
      is dependent on CD4(+) T cells. Immunodeficiencies that present with defects in
      the antibody response have provided insights into the molecular mechanisms of B
      cell responses and the provision of T cell help. One such immunodeficiency is X
      linked lymphoproliferative disease (XLP), which results from mutations in SH2D1A,
      the gene encoding SLAM-associated protein (SAP). Patients with XLP present with
      humoral defects characterized by hypogammaglobulinemia. We now know that SAP,
      through its signaling downstream of multiple members of the signaling lymphocytic
      activation molecule (SLAM) family of cell surface receptors, plays a crucial role
      in many aspects of this immune response. Here, we discuss the role of SAP in the
      generation of humoral immunity, particularly T cell-dependent antibody responses
      and the generation of germinal centers.

PMID- 21091717
TI  - Life-threatening infectious diseases of childhood: single-gene inborn errors of
      immunity?
AB  - The hypothesis that inborn errors of immunity underlie infectious diseases is
      gaining experimental support. However, the apparent modes of inheritance of
      predisposition or resistance differ considerably among diseases and among
      studies. A coherent genetic architecture of infectious diseases is lacking. We
      suggest here that life-threatening infectious diseases in childhood, occurring in
      the course of primary infection, result mostly from individually rare but
      collectively diverse single-gene variations of variable clinical penetrance,
      whereas the genetic component of predisposition to secondary or reactivation
      infections in adults is more complex. This model is consistent with (i) the high
      incidence of most infectious diseases in early childhood, followed by a steady
      decline; (ii) theoretical modeling of the impact of monogenic or polygenic
      predisposition on the incidence distribution of infectious diseases before
      reproductive age; (iii) available molecular evidence from both monogenic and
      complex genetics of infectious diseases in children and adults; (iv) current
      knowledge of immunity to primary and secondary or latent infections; (v) the
      state of the art in the clinical genetics of noninfectious pediatric and adult
      diseases; and (vi) evolutionary data for the genes underlying single-gene and
      complex disease risk. With the recent advent of new-generation deep resequencing,
      this model of single-gene variations underlying severe pediatric infectious
      diseases is experimentally testable.

PMID- 21091718
TI  - Allogeneic mesenchymal stem cells prevent allergic airway inflammation by
      inducing murine regulatory T cells.
AB  - BACKGROUND: Adult bone marrow-derived mesenchymal stem cells (MSC) possess potent
      immune modulatory effects which support their possible use as a therapy for
      immune-mediated disease. MSC induce regulatory T cells (T(reg)) in vitro although
      the in vivo relevance of this is not clear. OBJECTIVE: This study addressed the
      hypothesis that adult bone marrow derived-MSC would prevent the pathology
      associated with allergen-driven airway inflammation, and sought to define the
      effector mechanism. METHODS: The influence of allogeneic MSC was examined in a
      model system where T(reg) induction is essential to prevent pathology. This was
      tested using a combination of a model of ovalbumin-driven inflammation with
      allogeneic MSC cell therapy. RESULTS: Systemic administration of allogeneic MSC
      protected the airways from allergen-induced pathology, reducing airway
      inflammation and allergen-specific IgE. MSC were not globally suppressive but
      induced CD4(+) FoxP3(+) T cells and modulated cell-mediated responses at a local
      and systemic level, decreasing IL-4 but increasing IL-10 in bronchial fluid and
      from allergen re-stimulated splenocytes. Moderate dose cyclophosphamide protocols
      were used to differentially ablate T(reg) responses; under these conditions the
      major beneficial effect of MSC therapy was lost, suggesting induction of T(reg)
      as the key mechanism of action by MSC in this model. In spite of the elimination
      of T(reg) , a significant reduction in airway eosinophilia persisted in those
      treated with MSC. CONCLUSION: These data demonstrate that MSC induce T(reg) in
      vivo and reduce allergen-driven pathology. Multiple T(reg) dependent and
      independent mechanisms of therapeutic action are employed by MSC.

PMID- 21091716
TI  - Neurokinin-1 receptor: functional significance in the immune system in reference
      to selected infections and inflammation.
AB  - The G protein-coupled receptor (GPCR), neurokinin-1 receptor (NK1R), and its
      preferred ligand, substance P (SP), are reviewed in relationship to the immune
      system and selected infections. NK1R and SP are ubiquitous throughout the animal
      kingdom. This important pathway has unique functions in numerous cells and
      tissues. The interaction of SP with its preferred receptor, NK1R, leads to the
      activation of nuclear factor-kappa B (NF-kappaB) and proinflammatory cytokines.
      NK1R has two isoforms, both a full-length and a truncated form. These isoforms
      have different functional significances and differ in cell signaling capability.
      The proinflammatory signals modulated by SP are important in bacterial, viral,
      fungal, and parasitic diseases, as well as in immune system function. The SP-NK1R
      system is a major class 1, rhodopsin-like GPCR ligand-receptor interaction.

PMID- 21091719
TI  - Second to fourth digit ratios, male genital development and reproductive health:
      a clinical study among fertile men and testis cancer patients.
AB  - Second- to fourth-digit length ratio, 2D:4D, is a marker of testosterone level
      during foetal life that was found associated with sperm concentration or
      testosterone levels in some studies, but not in others, a difference possibly
      related to the way the ratio is assessed. In this study, 2D:4D was assessed in
      122 men partners of pregnant women and in 71 testicular cancer patients using a
      new method based on direct measurements of finger lengths. In addition, we
      investigated the association between 2D:4D, birth weight, testicular volume,
      semen quality and time to pregnancy. A validation study of the method
      demonstrated high reliability and reproducibility. Neither digit lengths nor
      2D:4D significantly differed in both groups of men. We found a significant
      negative association between 2D:4D and birth weight in testicular cancer
      patients. In fertile men, 2D:4D was associated with testicular volume (r=-0.36,
      p<0.001), total sperm number (r=-0.18, p=0.04) and time to pregnancy (r=0.24,
      p<0.02). In addition, participants with a history of epididymal cyst had a
      significantly higher 2D:4D than those without cysts. In conclusion, all
      significant findings indicate that the human male reproductive function is
      negatively related to 2D:4D. However, 2D:4D for testicular cancer patients does
      not point to a hormonal imbalance during foetal life as the common cause for
      developing germ-cell cancer. Such results obtained, thanks to an easy, direct and
      reliable method for measuring finger lengths, suggest the usefulness of this new
      tool in fertility studies as well as for studying men with developmental
      disorders of the reproductive tract.

PMID- 21091720
TI  - TaqMan real-time PCR assay for relative quantification of white spot syndrome
      virus infection in Penaeus monodon Fabricius exposed to ammonia.
AB  - White spot disease is caused by a highly virulent pathogen, the white spot
      syndrome virus (WSSV). The disease is usually triggered by changes in
      environmental parameters causing severe losses to the shrimp industry. This study
      was undertaken to quantify the relative WSSV load in shrimp exposed to ammonia,
      using a TaqMan-based real-time PCR, and their subsequent susceptibility to WSSV.
      Shrimp were exposed to different levels of total ammonia nitrogen (TAN) (8.1, 3.8
      and 1.1 mg L-1) for 10 days and challenged with WSSV by feeding WSSV-positive
      shrimp. WSSV was detected simultaneously in haemolymph, gills and pereopods at
      four hours post-infection. The TaqMan real-time PCR assay showed a highly dynamic
      detection limit that spanned over 6 log10 concentrations of DNA and high
      reproducibility (standard deviation 0.33-1.42) and small correlation of
      variability (CV) (1.89-3.85%). Shrimp exposed to ammonia had significantly higher
      (P < 0.01) WSSV load compared to the positive control, which was not exposed to
      ammonia. Shrimp exposed to 8.1 mg L-1 of TAN had the highest (P < 0.01) WSSV load
      in all three organs in comparison with those exposed to 3.8 and 1.1 mg L-1 of
      TAN. However, haemolymph had significantly higher (P < 0.01) viral load compared
      to the gills and pereopods. Results showed that shrimp exposed to ammonia levels
      as low as 1.1 mg L-1 (TAN) had increased susceptibility to WSSV.

PMID- 21091721
TI  - Molecular diagnosis of Myxobolus spirosulcatus associated with encephalomyelitis
      of cultured yellowtail, Seriola quinqueradiata Temminck & Schlegel.
AB  - Mass mortality of cultured yellowtail, Seriola quinqueradiata, has recently been
      reported from fish farms in western Japan. Previous studies revealed that
      diseased fish were characterized by encephalomyelitis and presporogonic stages of
      a myxosporean-like parasite in the spinal cord. However, the parasite has
      remained unidentified because of the lack of mature stages being present. Thus,
      in the present study, analysis of the small subunit ribosomal DNA (18S rDNA) of
      the parasite as well as in situ hybridization (ISH) studies using histological
      sections of the infected tissue was conducted. The 18S rDNA of the myxosporean
      had higher sequence similarities with those of bile-duct-infecting myxosporeans
      rather than those infecting nervous tissues and was identified as Myxobolus
      spirosulcatus. The ISH using specific probes demonstrated that the DNA amplified
      was derived from the multinuclear organisms found in histological sections. A
      highly sensitive and specific PCR-based assay for M. spirosulcatus was developed,
      which revealed a high prevalence of infection in cultured yellowtail that
      exhibited the clinical signs of encephalomyelitis.

PMID- 21091722
TI  - Morphology and distribution of granulomatous inflammation in freshwater
      ornamental fish infected with mycobacteria.
AB  - Mycobacteriosis in fish is a chronic progressive ubiquitous disease caused by
      Mycobacterium marinum, M. gordonae and M. fortuitum in most cases. The aim of
      this study was to describe the morphology and distribution of lesions in 322
      freshwater ornamental fish across 36 species. Granulomatous inflammation was
      diagnosed by gross examination and histopathology testing in 188 fish (58.4%);
      acid-fast rods (AFR) were determined in only 96 (51.1%) fish from 19 species
      after Ziehl-Neelsen staining. The most often affected organs with AFR were the
      kidney (81.2%), digestive tract (54.1%), liver (48.2%), spleen (45.9%) and skin
      (21.2%); sporadically, AFR were found in the branchiae (9.4%) and gonads (4.7%).
      In 14 randomly selected fish originating from four different fish tanks, the
      distribution of mycobacterial infection was studied by culture examination of the
      skin, gills, muscle tissue, digestive tract, liver, spleen and kidney. In 12
      fish, the species M. marinum, M. gordonae, M. fortuitum, M. triviale, and M.
      avium subsp. hominissuis (serotypes 6 and 8 and genotype IS901- and IS1245+) were
      detected; mixed infection caused by different mycobacterial species was
      documented in five of them.

PMID- 21091723
TI  - Dietary fatty acids and inflammation in the vertebral column of Atlantic salmon,
      Salmo salar L., smolts: a possible link to spinal deformities.
AB  - Vegetable oils (Vo) are an alternative to fish oil (Fo) in aquaculture feeds.
      This study aimed to evaluate the effect of dietary soybean oil (Vo diet), rich in
      linoleic acid, and of dietary fish oil (Fo diet) on the development of spinal
      deformities under bacterial lipopolysaccharide (LPS)-induced chronic inflammation
      conditions in Atlantic salmon, Salmo salar L. Fish [25 g body weight (BW)] were
      fed the experimental diets for 99 days. On day 47 of feeding (40 g BW), fish were
      subjected to four experimental regimes: (i) intramuscular injections with LPS,
      (ii) sham-injected phosphate-buffered saline (PBS), (iii) intraperitoneally
      injected commercial oil adjuvant vaccine, or (iv) no treatment. The fish
      continued under a common feeding regime in sea water for 165 more days. Body
      weight was temporarily higher in the Vo group than in the Fo group prior to
      immunization and was also affected by the type of immunization. At the end of the
      trial, no differences were seen between the dietary groups. The overall
      prevalence of spinal deformities was approximately 14% at the end of the
      experiment. The Vo diet affected vertebral shape but did not induce spinal
      deformities. In groups injected with LPS and PBS, spinal deformities ranged
      between 21% and 38%, diet independent. Deformed vertebrae were located at or in
      proximity to the injection point. Assessment of inflammatory markers revealed
      high levels of plasma prostaglandin E2 (PGE2) in the Vo-fed and LPS-injected
      groups, suggesting an inflammatory response to LPS. Cyclooxigenase 2 (COX-2) mRNA
      expression in bone was higher in fish fed Fo compared to Vo-fed fish. Gene
      expression of immunoglobulin M (IgM) was up-regulated in bone of all LPS-injected
      groups irrespective of dietary oil. In conclusion, the study suggests that Vo is
      not a risk factor for the development of inflammation-related spinal deformities.
      At the same time, we found evidence that localized injection-related processes
      could trigger the development of vertebral body malformations.

PMID- 21091724
TI  - Simple and direct detection of Aeromonas hydrophila infection in the goldfish,
      Carassius auratus (L.), by dot blotting using specific monoclonal antibodies.
AB  - A combination of eight isolates of Aeromonas hydrophila was used to produce
      monoclonal antibodies (MAbs). Ten different groups of MAbs specific to Aeromonas
      were selected. The first five groups of MAbs demonstrated high specificity and
      bound to only one or two isolates of A. hydrophila. The sixth and the seventh
      groups of MAbs were A. hydrophila specific. They recognized seven of eight A.
      hydrophila isolates (AH1, 2, 3, 4, 5, 6, 8); however, the MAb in the seventh
      group also showed cross-reactivity to one isolate of Aeromonas caviae (AC3). The
      eighth MAb group recognized two isolates of A. hydrophila (AH2 and AH5) and
      demonstrated cross-reactivity to one isolate of Aeromonas sobria (AS1) and one
      isolate of A. caviae (AC3). The tenth group of MAbs bound to all isolates of
      Aeromonas spp. tested (AH1-8, AS1-6, AC1-5, Aeromonas veronii and Aeromonas
      jandaei) without cross-reactivity to any of the other bacteria tested. MAbs in
      the ninth group showed similar specificity to those in the tenth group but did
      not recognize two isolates of A. sobria (AS4 and AS6) or A. jandaei. All the MAbs
      could be used to identify Aeromonas by dot blotting with a sensitivity ranging
      from 105 to 107 CFU mL-1. However, the sensitivity of detection was increased to
      102-103 CFU mL-1 after inoculation of the sample in tryptic soy broth for 3-6 h
      before performing the dot blotting. The dot blot method can be used for the
      direct detection of A. hydrophila infection in symptomatic and asymptomatic
      goldfish. This study demonstrated a convenient immunological tool that can be
      used for the direct detection of A. hydrophila and Aeromonas infections in a
      complex sample without the requirement for separation of the bacteria or
      isolation and biochemical tests.

PMID- 21091725
TI  - Comparative analysis of the phenotypic characteristics of high- and low-virulent
      strains of Edwardsiella tarda.
AB  - Edwardsiella tarda is a causative agent of edwardsiellosis in freshwater and
      marine fish. Extracellular enzymic, haemolytic, hydrophobic and serum resistance
      activities, haemagglutination, autoagglutination and siderophores of high- and
      low- virulent E. tarda strains were examined. The results revealed different
      haemagglutination, autoagglutination, haemolytic, hydrophobic and serum
      resistance activities in different strains. Analysis of extracellular proteins
      (ECPs) and outer membrane proteins (OMPs) demonstrated several major, low
      molecular weight, virulent-strain-specific proteins, which could be virulence
      related. Based on the database search with MALDI-TOF MS data, the closest
      homologies of the three protein bands Ed1, Ed2 and Ed3 were phosphotransferase
      enzyme family protein, nitrite reductase [NAD(P)H], large subunit and ATP
      dependent Lon protease, respectively. A comparison of pathogenicity of purified
      lipopolysaccharide (LPS) and lipid A from virulent and avirulent strains
      demonstrated that LPS was one of the virulence factors of the E. tarda isolates,
      and lipid A was a biologically active determinant of LPS.

PMID- 21091726
TI  - Evidence for synergism of the antimicrobial peptide piscidin 2 with antiparasitic
      and antioomycete drugs.
AB  - Piscidins are potent, broad-spectrum, host-produced antimicrobial peptides (AMPs)
      that appear to constitute the most common AMP family in teleost fish. Here, we
      show that piscidin 2 has potent activity against the water mould Saprolegnia, one
      of the most important pathogens of freshwater fish. The minimum oomyceticidal
      concentration (MOC100) of piscidin 2 against zoospores of three pathogenic
      isolates of Saprolegnia ranged from 12.5 to 25.0 MUg mL-1. This piscidin
      concentration is well within levels that have been estimated to be present in at
      least some fish (1-32.5 MUg mL-1). In the presence of either copper or malachite
      green, two drugs commonly used to treat water moulds, there was evidence for
      partial synergism (PSYN) with piscidin 2. There was also evidence for PSYN after
      exposure of the ciliate parasite Tetrahymena pyriformis to piscidin 2 plus
      copper. Our data provide further evidence that piscidins may be an important host
      defence against skin and gill pathogens and that the piscidin levels in host
      tissue might influence the success of drug treatments.

PMID- 21091727
TI  - Pharmacokinetic and pharmacodynamic modelling of marbofloxacin administered alone
      and in combination with tolfenamic acid in calves.
AB  - In a four-period, cross-over study, the fluoroquinolone antibacterial drug
      marbofloxacin (MB) was administered to calves, alone and in combination with the
      nonsteroidal anti-inflammatory drug tolfenamic acid (TA). Both drugs were
      administered intramuscularly (IM) at doses of 2 mg/kg. A tissue cage model of
      inflammation, based on the actions of the mild irritant carrageenan, was used to
      evaluate the pharmacokinetics (PK) of MB and MB in combination with TA. MB mean
      values of area under concentration-time curve (AUC) were 15.1 MUg.h/mL for serum,
      12.1 MUg.h/mL for inflamed tissue cage fluid (exudate) and 9.6 MUg.h/mL for
      noninflamed tissue cage fluid (transudate). Values of C(max) were 1.84, 0.35 and
      0.31 MUg/mL, respectively, for serum, exudate and transudate. Mean residence time
      (MRT) of 23.6 h (exudate) and 22.6 h (transudate) also differed significantly
      from serum MRT (8.6 h). Co-administration of TA did not affect the PK profile of
      MB. The pharmacodynamics of MB was investigated using a bovine strain of
      Mannheimia haemolytica. Time-kill curves were established ex vivo on serum,
      exudate and transudate samples. Modelling the ex vivo serum time-kill data to the
      sigmoid E(max) equation provided AUC(24 h) /MIC values required for
      bacteriostatic (18.3 h) and bactericidal actions (92 h) of MB and for virtual
      eradication of the organism was 139 h. Corresponding values for MB + TA were
      20.1, 69 and 106 h. These data were used to predict once daily dosage schedules
      for a bactericidal action, assuming a MIC(90) value of 0.24 MUg/mL, a dose of 2.6
      mg/kg for MB and 2.19 mg/kg for MB + TA were determined, which are similar to the
      currently recommended dose of 2.0 mg/kg.

PMID- 21091728
TI  - Analytical determination and pharmacokinetics of major metabolites of carbasalate
      calcium in broilers following oral administration.
AB  - As a newer anti-inflammatory agent, carbasalate calcium is used in various animal
      species. In this study, the pharmacokinetics of carbasalate calcium was
      investigated in broilers. Broilers, with body weight of 2.0 +/- 0.3 kg, were
      administrated carbasalate calcium soluble powder at a single dose of 40 mg/kg
      body weight orally. The plasma concentrations of its metabolites, aspirin (ASA),
      salicylic acid (SA) and gentisic acid (GA) were determined by LC-MS/MS method and
      the pharmacokinetic parameters were calculated by noncompartmental analysis.
      After oral administration of carbasalate calcium, the plasma drug concentration
      for ASA, SA and GA reached a peak (C(max) ) of 8.88 +/- 1.31, 42.6 +/- 4.62 and
      10.1 +/- 2.16 MUg/mL at 0.170, 2.00 and 2.00 h, respectively. The terminal half
      life (t(1/2lambdaz) ) of ASA, SA and GA was 11.2 +/- 8.04, 23.7 +/- 17.1 and 28.6
      +/- 4.90 h, respectively. In conclusion, analytical method for the quantification
      of ASA, SA and GA in plasma in the broilers was developed and validated. In
      broilers, carbasalate calcium is quickly metabolized in ASA and ASA is rapidly
      converted to SA and one of the metabolites of SA is GA.

PMID- 21091729
TI  - Renin-angiotensin system blocker use may be associated with suppression of atrial
      fibrillation recurrence after pulmonary vein isolation.
AB  - INTRODUCTION: An additional approach may be essential to reduce recurrences of
      atrial fibrillation (AF) after pulmonary vein isolation (PVI). We examined the
      efficacy of renin-angiotensin system blockers (RAS-B) in suppressing AF
      recurrences after PVI. METHODS AND RESULTS: We retrospectively studied 264
      consecutive patients (195 male, median age: 63 years) who underwent successful
      PVI of paroxysmal (n = 94) or persistent AF (n = 170). RAS-B treatment was
      performed in 145 patients (angiotensin-converting enzyme inhibitors; n = 13,
      angiotensin receptor blockers; n = 129, both; n = 3). Echocardiography was
      performed before and 3 months after the ablation to examine the occurrence of
      left atrial structural reverse remodeling (LA-RR). After a median follow-up of
      195 (interquartile range: 95-316) days, AF recurred in 51 (19.3%) patients. A Cox
      regression analysis revealed that AF recurrence was significantly lower in the
      patients with RAS-B than in those without (hazard ratio [HR] = 0.41 [95%
      confidence interval (CI): 0.23-0.71], P = 0.002). After a multivariate adjustment
      for potential confounders, the use of RAS-B (HR = 0.39 [95% CI: 0.19-0.77], P =
      0.007) and type of AF (HR = 0.30 [95% CI: 0.13-0.66], P = 0.003) were the
      independent predictors for AF recurrence during the entire follow-up. Although
      effect of RAS-B was not significant during the early follow-up (<3 month), it was
      the only independent predictor during the late follow-up (>3 months) (HR = 0.21
      [95% CI: 0.08-0.53], P = 0.001). There were no significant differences in LA-RR
      occurrence regarding RAS-B medication. The use of RAS-B was an independent
      predictor of late AF recurrences irrespective of an early LA-RR occurrence.
      CONCLUSIONS: Treatment with RAS-B significantly reduced the AF recurrence after
      PVI. This benefit became more prominent 3 months after the PVI.

PMID- 21091730
TI  - A case of aborted sudden cardiac death and consequent extreme electrical storm
      secondary to a metastatic cardiac tumor.
AB  - We report a 43-year-old man with an implantable cardioverter defibrillator for
      aborted sudden cardiac death. He represents in extreme electrical storm with 111
      different ventricular fibrillation episodes. Successful treatment was achieved
      with multiple antiarrhythmic agents, mechanical ventilation, external shocks, and
      ultimately overdrive pacing. A cardiac magnetic resonance scan revealed two
      cardiac lesions that were later diagnosed as metastatic fibrosarcoma. This case
      highlights two very important and increasingly common cardiological dilemmas: the
      management of extreme electrical storm and the role of magnetic resonance imaging
      in aborted cardiac death patients with an apparent "normal" heart.

PMID- 21091731
TI  - Idiopathic premature ventricular contractions arising from the intraventricular
      septum adjacent to the his bundle.
AB  - A 57-year-old woman with idiopathic premature ventricular contractions (PVCs)
      exhibiting a left bundle branch block and left inferior axis QRS morphology
      underwent electrophysiological testing. Mapping revealed that the earliest
      ventricular activation times during the PVCs recorded on either side of the
      interventricular septum were the same and no excellent pace maps were reproduced
      at these sites. Successful radiofrequency catheter ablation was achieved in the
      right ventricular septum adjacent to the recording site of the His bundle
      electrogram. These findings suggested that the origin of this PVC was located in
      the intraventricular septum rather than the endocardial surface.

PMID- 21091732
TI  - Successful ablation for atrioventricular nodal reentrant tachycardia in a patient
      with left atrial isomerism.
AB  - Left atrial isomerism (LAI) is characterized by the presence of two
      morphologically identical atria. It is commonly associated with conduction
      defects. We report a case of LAI presenting with highly symptomatic
      atrioventricular nodal reentrant tachycardia, which was cured by ablation.

PMID- 21091733
TI  - "Electrically silent" pulmonary veins connecting to the right atrium: does the
      atrium make the difference?
AB  - Pulmonary veins (PVs) usually drain into the left atrium (LA) and are frequently
      targeted for electrical isolation, since it became evident that PVs may trigger
      and maintain paroxysmal atrial fibrillation (AF). We present a patient with right
      sided PVs anomalously connecting to the right atrium with lack of electrical PV
      atrial connection. Therefore, isolation of the left veins was performed resulting
      in freedom from AF as shown during a midterm follow-up. These findings indicate
      that PV connection to the LA may be a prerequisite for the arrhythmogenic
      properties of the PVs causing AF.

PMID- 21091734
TI  - Induction of ventricular tachycardia by alternate current due to an
      insufficiently grounded electrical system.
AB  - Detection of electromagnetic interference followed by inappropriate therapy by
      implantable cardioverter-defibrillators (ICDs) has been well documented in
      several case reports as well as in follow-up studies. This is a report of a case
      where electromagnetic interference induced ventricular tachycardia, with
      appropriate detection and treatment by the patient's ICD.

PMID- 21091735
TI  - Cardiac resynchronization therapy in patients with right ventricular pacing
      induced cardiomyopathy.

PMID- 21091736
TI  - Atrial fibrillation: what have recent trials taught us regarding pharmacologic
      management of rate and rhythm control?
AB  - The management of atrial fibrillation (AF) focuses on control of heart rate,
      correction of rhythm disturbance, prophylaxis of thromboembolism, treatment of
      underlying disorders, and pathophysiologic mechanisms, and more recently on
      costs, hospitalizations, and other AF consequences. The goals of therapy are to
      reduce morbidity and mortality and improve quality of life (QOL). Several large
      studies have examined the relative efficacy of rhythm- versus rate-control
      strategies with respect to these outcomes, and have largely failed to demonstrate
      a survival advantage with either approach by intention-to-treat analysis--both in
      patients with and without heart failure (HF). However, the results do not support
      the hypothesis that rate control is preferable as first-line therapy for AF with
      respect to survival and do not disprove the hypothesis that maintenance of sinus
      rhythm is preferable to the continuation of AF, particularly if rate control
      fails to restore adequate QOL or if selective approaches are employed. Many post
      hoc analyses and substudies have assessed QOL, functional status, and exercise
      tolerance, with the majority demonstrating important benefits associated with
      achievement of rhythm control. Moreover, some subanalyses and additional trials
      have suggested that sinus rhythm can be associated with longer survival,
      including in patients with HF. In addition, ATHENA demonstrated that a drug,
      dronedarone, could improve the composite endpoint of cardiovascular
      hospitalizations and all-cause mortality in a carefully selected, high-risk,
      nonpermanent AF population, in addition to its recognized reduction in AF. This
      review examines the clinical outcomes of several important AF trials, discusses
      the limitations in applying the major morbidity/mortality findings to everyday
      clinical practice, and summarizes the lessons learned.

PMID- 21091737
TI  - Evaluation of patients with "faint" in an American teaching hospital: a dire need
      for a standardized approach.
AB  - BACKGROUND: Fainting is a major healthcare problem with significant morbidity,
      mortality, and healthcare cost. We sought to assess the appropriateness of
      current clinical practice when compared to a guideline-based algorithm. METHODS:
      The records of 100 consecutive patients who presented with faint and were
      referred to the University of Utah for further evaluation by specialists were
      reviewed. We analyzed the clinical characteristics, tests performed, diagnosis
      made, and number of admissions. In addition, we applied a guideline-based
      algorithm to assess the appropriateness of these evaluations. RESULTS: The mean
      age was 49 +/- 21 years with 57% being female. One-third presented with their
      first event. Structural heart disease was present in 22% of the cases. Twelve
      (36%) of 32 admissions were inappropriate. There was an underutilization of
      orthostatic testing, carotid sinus massage, and implantable loop recorder and
      overutilization of imaging studies and neurologic consultation. Specifically,
      active standing and tilt-table testing were performed in only 24% and 7% of the
      cases, respectively, none of the patients had carotid sinus massage despite 26%
      of them being >=65 years old, and only 3% of the patients received an implantable
      loop recorder. With the current practice, a final diagnosis was made in 45 cases
      with 17 (38%) of the 45 final diagnoses not being sufficiently supported by the
      completeness of the evaluation. CONCLUSION: With the current practice at a major
      university hospital, the cause of faint was unexplained in a high number of
      cases. Our findings highlight the need for a standardized approach to patients
      presenting with faint.

PMID- 21091738
TI  - Noncavotricuspid isthmus-dependent right atrial tachycardia after paroxysmal
      atrial fibrillation ablation.
AB  - BACKGROUND: Atrial tachycardia (AT) is commonly encountered after atrial
      fibrillation (AF) ablation. But no study exclusively on noncavotricuspid isthmus
      dependent right AT (NCTI-RAT) post-AF ablation has been reported. The present
      study aims to describe its prevalence, electrophysiological mechanisms, and
      ablation strategy and to further discuss its relationship with AF. METHODS: From
      July 2006 to November 2009, 350 consecutive patients underwent catheter ablation
      for paroxysmal AF. A total of seven patients (2.0%) developed NCTI-RAT after left
      atrium ablation for AF. In these highly selected patients (two male, mean age 54
      +/- 11 years, mean left atrium diameter of 34 +/- 7 cm), all had circumferential
      pulmonary vein isolation in their initial procedures and three of them had
      additional complex fractionated electrograms ablation in the left atrium and the
      coronary sinus. RESULTS: Totally, nine NCTI-RATs were mapped and successfully
      ablated in the right atrium with a mean cycle length of 273 +/- 64 ms in seven
      patients. Five ATs in three patients were electrophysiologically proved to be
      macroreentry and the remaining four were focal activation. All the ATs were
      successfully abolished by catheter ablation. After a mean follow-up of 29 +/- 15
      months post-AT ablation, all patients were free of AT and AF off antiarrhythmic
      drugs. CONCLUSIONS:  NCTI-RAT is relatively less common post-AF ablation.
      Totally, 2.0% of paroxysmal AF patients were revealed to have NCTI-RAT.

PMID- 21091739
TI  - Henry Cuthbert Bazett (1885-1950)--the man behind the QT interval correction
      formula.
AB  - The "Bazett formula" is used for correcting the observed QT interval and is named
      after Henry Cuthbert Bazett who was born in England in 1885. He studied medicine
      and worked in Oxford and served in the British Medical Corps during World War I.
      In 1920, Bazett published his seminal paper on the different intervals length of
      the electrocardiogram recordings in a small group of healthy individuals, and
      proposed a formula for correcting the QT length for heart rate. Later, he moved
      to the University of Pennsylvania, in Philadelphia, and from 1931 until his death
      in 1950, he served as head of the Department of Physiology and a leader of the
      American Society of Physiology. Bazett's scientific work was largely concerned
      with temperature control, circulation, and blood volume, and he contributed
      greatly to the study of circulation in humans by using invasive catheterization.

PMID- 21091740
TI  - Antiarrhythmic effect of reverse electrical remodeling associated with cardiac
      resynchronization therapy.
AB  - BACKGROUND: Antiarrhythmic and proarrhythmic effects of cardiac resynchronization
      therapy (CRT) remain controversial. We hypothesized that reverse electrical
      remodeling (RER) with CRT is associated with reduced frequency of ventricular
      tachyarrhythmias (VTs). METHODS: The width of native and paced QRS was measured
      in lead II electrocardiogram before and 13 +/- 7 months after implantation of a
      CRT defibrillator device in 69 patients (mean age 66.3 +/- 13.9; 39 males [83%])
      with bundle branch block (BBB) (41 patients with left BBB and three patients with
      bifascicular block) or nonspecific intraventricular conduction delay (25
      patients, 36%), and New York Heart Association class III-IV heart failure.
      Biventricular pacing was inhibited for 10 seconds to record native QRS. RER was
      defined as a decrease in the native QRS duration >=10 ms compared to preimplant.
      Patients were followed prospectively 24 +/- 13 months after assessment for
      electrical remodeling. RESULTS: RER was observed in 22 patients (32%), among whom
      QRS duration decreased by 30.9 +/- 14.1 ms (P < 0.00001) with similar heart rate
      and QRS morphology. Native QRS duration increased by 10.3 +/- 16.6 ms in the
      other 47 patients (68%) (P = 0.0001). Baseline mean ejection fraction did not
      differ between patients with and those without RER (24.9 +/- 10.0 vs 24.2 +/-
      8.6%, NS). During 2 +/- 1 years of further follow-up, 19 patients had VTs and 12
      patients died. RER was associated with a fourfold decrease in the risk of death
      or sustained VTs requiring appropriate implantable cardioverter-defibrillator
      therapies, whichever came first (hazard ratio 0.25; 95% confidence interval 0.08
      0.85; P = 0.026). CONCLUSION: RER of the native conduction with CRT is associated
      with decreased mortality and antiarrhythmic effect of CRT.

PMID- 21091741
TI  - Safety and feasibility of cephalic venous access for cardiac resynchronization
      device implantation.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) devices are usually implanted
      using subclavian vein access, which is associated with the risk of pneumothorax.
      We examined whether cephalic venous access is an effective alternative to
      subclavian access by the Seldinger technique for CRT delivery. METHODS: We
      retrospectively analyzed all CRT procedures performed over a 1-year period at our
      center with respect to the access methods, primary success rate, safety, and
      efficiency. RESULTS: We retrospectively analyzed 103 consecutive primary
      implantation procedures. The procedure was accomplished using cephalic access
      alone for 54 of 61 (89%) CRT implants attempted by this route. The overall
      success rate was 100% (61/61) with additional use of subclavian access. CRT
      implantation via subclavian vein access was successful in 37 of 42 (88%) (P <
      0.05 vs cephalic group). The procedure duration was shorter for the cephalic
      group (118 +/- 39 vs 147 +/- 36 minutes, P < 0.0005) as were the screening times
      and radiation exposure (15 +/- 9 vs 27 +/- 18 minutes and 4.7 +/- 5.8 vs 9.3 +/-
      9.1 Gcm(2) , both P < 0.01). In the cephalic group, procedure duration and
      radiation exposure diminished significantly with increasing experience of the
      technique. Complications occurred in two of 61 (3.3%) cases in the cephalic group
      and three of 42 (7.1%) in the subclavian group (P = NS). CONCLUSION: CRT devices
      can be implanted using cephalic access alone in a large majority of cases. This
      approach is safe and efficient.

PMID- 21091742
TI  - Interatrial septum pacing decreases atrial dyssynchrony on strain rate imaging
      compared with right atrial appendage pacing.
AB  - BACKGROUND: Interatrial septum pacing (IAS-P) decreases atrial conduction delay
      compared with right atrial appendage pacing (RAA-P). We evaluate the atrial
      contraction with strain rate of tissue Doppler imaging (TDI) during sinus
      activation or with IAS-P or RAA-P. METHODS: Fifty-two patients with permanent
      pacemaker for sinus node disease were enrolled in the study. Twenty-three
      subjects were with IAS-P and 29 with RAA-P. The time from end-diastole to peak
      end-diastolic strain rate was measured and corrected with RR interval on
      electrocardiogram. It was defined as the time from end-diastole to peak end
      diastolic strain rate (TSRc), and the balance between maximum and minimum TSRc at
      three sites (DeltaTSRc) was compared during sinus activation and with pacing
      rhythm in each group. RESULTS: There were no significant differences observed in
      general characteristics and standard echocardiographic parameters except the
      duration of pacing P wave between the two groups. The duration was significantly
      shorter in the IAS-P group compared with the RAA-P group (95 +/- 34 vs 138 +/-
      41; P = 0.001). TSRc was significantly different between sinus activation and
      pacing rhythm (36.3 +/- 35.7 vs 61.6 +/- 36.3; P = 0.003) in the RAA-P group,
      whereas no significant differences were observed in the IAS-P group (25.4 +/-
      12.1 vs 27.7 +/- 14.7; NS). During the follow-up (mean 2.4 +/- 0.7 years), the
      incidence of paroxysmal atrial fibrillation (AF) conversion to permanent AF was
      not significantly different between the two groups. CONCLUSIONS: IAS-P decreased
      the contraction delay on atrial TDI compared to RAA-P; however, it did not
      contribute to the reduction of AF incidence in the present study.

PMID- 21091743
TI  - Intermittent single nontracked P waves immediately after dual-chamber pacemaker
      implantation for complete AV block. What is the mechanism?

PMID- 21091744
TI  - High-sensitivity C-reactive protein as a predictor of atrial fibrillation
      recurrence after primary circumferential pulmonary vein isolation.
AB  - BACKGROUND: Atrial fibrillation (AF) recurrence after circumferential pulmonary
      vein isolation (CPVI) is difficult to predict. Inflammation is associated with
      the development of AF. Inflammatory markers, such as high sensitivity C-reactive
      protein (hsCRP), are related to AF development via atrial remodeling. However, it
      is unknown whether plasma hsCRP concentration before CPVI can be used as a
      predictor for AF recurrence. METHODS: A total of 121 patients without structural
      heart disease who underwent primary CPVI by a single operator were included in
      the study (paroxysmal/persistent AF: 77/44). Left atrial diameter was measured by
      transesophageal echocardiography. Plasma hsCRP concentration was determined by
      enzyme-linked immunosorbent assay. Based on the follow-up outcomes, patients were
      divided into two groups, a recurrence group and a nonrecurrence group. AF
      recurrence was defined as AF or atrial flutter or atrial tachycardia episodes
      lasting for >=30 s during regular follow-up (>12 months). RESULTS: A total of 36
      (29.8%) patients (paroxysmal/persistent AF: 19 [24.7%]/17 [38.6%]) had AF
      recurrence in a mean 23 (range, 12-44) month follow-up period. The plasma hsCRP
      concentration in the recurrence group was significantly higher than that in the
      nonrecurrence group for all patients (median [quartile range] 2.22 [1.97] mg/L vs
      0.89 [1.30] mg/L, P < 0.001), for patients with paroxysmal AF (2.12 [2.78] mg/L
      vs 0.84 [1.15] mg/L, P = 0.028), and for those with persistent AF (2.29 [1.08]
      mg/L vs 0.89 [1.53] mg/L, P = 0.005). Multiple logistic regression analyses
      showed that the higher level of the plasma hsCRP (P < 0.001) was a significant
      prognostic predictor of AF recurrence, both for patients with paroxysmal AF (P =
      0.012) and those with persistent AF (P = 0.003). CONCLUSION: Plasma hsCRP
      concentration before CPVI was associated with AF recurrence after primary CPVI
      procedure for both paroxysmal and persistent AF patients. Plasma hsCRP
      concentration could play a role in prediction of AF recurrence after primary
      CPVI.

PMID- 21091745
TI  - Physiopathologic correlates of intrathoracic impedance in chronic heart failure
      patients.
AB  - BACKGROUND: Increased plasma levels of amino-terminal fraction of brain
      natriuretic peptide (NT-proBNP) and alterations of diastolic filling as described
      by Doppler transmitral flow pattern are well-known markers of decompensated heart
      failure (HF). Recently, some implantable defibrillators have allowed monitoring
      of intrathoracic impedance, which is related to lung water content, potentially
      indicating HF deterioration. The aim of this study was to assess the correlation
      between intrathoracic impedance and NT-proBNP and echo-Doppler transmitral flow
      indexes. METHODS: Data were collected from 111 HF patients, in six Italian
      centers. All patients were on optimal medical therapy. Device diagnostics,
      echographic data, NT-proBNP determination, and clinical status as assessed by the
      Heart Failure Score (HFS) were registered at baseline, at bimonthly visits, and
      at unscheduled examinations due to HF decompensation or device alerts. RESULTS:
      Over a median follow-up of 413 days, 955 examinations were performed.
      Intrathoracic impedance was significantly correlated with NT-proBNP (P = 0.013)
      and with mitral E-wave deceleration time (DtE) (P = 0.017), but not with HFS. At
      the time of confirmed alert events, NT-proBNP was significantly higher than
      during confirmed nonalert event examinations; DtE did not differ, whereas
      impedance was significantly lower. CONCLUSION: A decrease in intrathoracic
      impedance is inversely correlated with NT-proBNP and directly correlated with
      DtE. Intrathoracic impedance monitoring therefore has the physiologic basis for
      being a useful tool to identify early HF decompensation.

PMID- 21091747
TI  - Idiopathic mitral annular PVCs with multiple breakouts and preferential
      conduction unmasked by radiofrequency catheter ablation.
AB  - A 39-year-old man with idiopathic monomorphic premature ventricular contractions
      (PVCs), exhibiting a right bundle branch block and inferior axis QRS morphology,
      underwent electrophysiological testing. After a radiofrequency (RF) application
      to the anterior mitral annulus (MA) eliminated the spontaneous PVC morphology, a
      second PVC morphology occurred. Pacing from the first ablation site exhibited an
      excellent match to the second PVCs with a long stimulus to QRS interval. An RF
      application delivered near the first lesion eliminated all PVCs. The MA PVCs in
      this case exhibited a single origin with multiple breakouts and preferential
      conduction that were unmasked by RF ablation.

PMID- 21091746
TI  - An algorithm to predict the site of origin of focal atrial tachycardia.
AB  - BACKGROUND: Only a few algorithms for predicting the site of origin of focal
      atrial tachycardia (AT) have been reported. We aimed to develop a new and more
      effective algorithm. METHODS: Surface 12-lead electrocardiograms were collected
      during tachycardia and sinus rhythm in 61 patients who received successful
      radiofrequency ablation. P-wave polarities, durations, and amplitudes were
      analyzed. Predictive values of the most significant parameters were determined.
      An algorithm was then developed and prospectively evaluated in 30 new consecutive
      AT patients. RESULTS: Thirty-six percent (22/61) of the foci were located at the
      ostium of coronary sinus (CS). Other common foci included pulmonary veins (PVs, n
      = 15), right atrial appendage (RAA, n = 7), parahisian area (n = 7), and crista
      terminalis (CT, n = 3). Positive P waves in inferior leads (II, III, and aVF) and
      a negative P wave in lead aVR indicated high atrial origins (high CT, superior
      PVs, and RAA, defined as Area A), with a sensitivity of 95% and a specificity of
      90%. Negative P waves in inferior leads and a positive P wave in lead aVR
      suggested right low septal origins (CS ostium and inferior tricuspid annulus,
      defined as Area B), with good sensitivity and specificity (88% and 89%,
      respectively). This new P-wave diagnostic algorithm correctly identified the site
      of origin in 90% of AT cases. CONCLUSION: Combination of data from multiple leads
      and regrouping of sites of origin provides a better predictive value.

PMID- 21091748
TI  - Ablation of atrioventricular nodal reentrant tachycardia in a patient with
      tricuspid atresia guided by electroanatomic mapping.
AB  - We describe a case of ablation of atrioventricular nodal reentrant tachycardia in
      a patient with tricuspid atresia and L-malposition of great vessels using an
      electroanatomical mapping system integrated with cardiac magnetic resonance
      imaging. Atrial activation mapping during tachycardia identified the retrograde
      fast pathway proximal to the His bundle, observed in the left interatrial septum.
      Ablation was successfully completed below this area. Map integration with the
      patient's anatomy allowed a safe, individualized procedure.

PMID- 21091749
TI  - The discrete Weibull distribution: an alternative for correlated counts with
      confirmation for microbial counts in water.
AB  - Distributions of pathogen counts in treated water over time are highly skewed,
      power-law-like, and discrete. Over long periods of record, a long tail is
      observed, which can strongly determine the long-term mean pathogen count and
      associated health effects. Such distributions have been modeled with the Poisson
      lognormal (PLN) computed (not closed-form) distribution, and a new discrete
      growth distribution (DGD), also computed, recently proposed and demonstrated for
      microbial counts in water (Risk Analysis 29, 841-856). In this article, an error
      in the original theoretical development of the DGD is pointed out, and the
      approach is shown to support the closed-form discrete Weibull (DW). Furthermore,
      an information-theoretic derivation of the DGD is presented, explaining the fit
      shown for it to the original nine empirical and three simulated (n = 1,000) long
      term waterborne microbial count data sets. Both developments result from a theory
      of multiplicative growth of outcome size from correlated, entropy-forced cause
      magnitudes. The predicted DW and DGD are first borne out in simulations of
      continuous and discrete correlated growth processes, respectively. Then the DW
      and DGD are each demonstrated to fit 10 of the original 12 data sets, passing the
      chi-square goodness-of-fit test (alpha= 0.05, overall p = 0.1184). The PLN was
      not demonstrated, fitting only 4 of 12 data sets (p = 1.6 * 10(-8) ), explained
      by cause magnitude correlation. Results bear out predictions of monotonically
      decreasing distributions, and suggest use of the DW for inhomogeneous counts
      correlated in time or space. A formula for computing the DW mean is presented.

PMID- 21091750
TI  - Challenges in development and implementation of health-risk-based soil quality
      guidelines: Turkey's experience.
AB  - Management of contaminated sites is a critical environmental issue around the
      world due to the human health risk involved for many sites and scarcity of
      funding. Moreover, clean-up costs of all contaminated sites to their background
      levels with existing engineering technologies may be financially infeasible and
      demand extended periods of operation time. Given these constraints, to achieve
      optimal utilization of available funds and prioritization of contaminated sites
      that need immediate attention, health-risk-based soil quality guidelines should
      be preferred over the traditional soil quality standards. For these reasons,
      traditional soil quality standards are being replaced by health-risk-based ones
      in many countries and in Turkey as well. The need for health-risk-based
      guidelines is clear, but developing these guidelines and implementation of them
      in contaminated site management is not a straightforward process. The goal of
      this study is to highlight the problems that are encountered at various stages of
      the development process of risk-based soil quality guidelines for Turkey and how
      they are dealt with. Utilization of different definitions and methodologies at
      different countries, existence of inconsistent risk assessment tools,
      difficulties in accessing relevant documents and reports, and lack of specific
      data required for Turkey are among these problems. We believe that Turkey's
      experience may help other countries that are planning to develop health-risk
      based guidelines achieve their goals in a more efficient manner.

PMID- 21091751
TI  - Growth hormone treatment in children with idiopathic short stature: correlation
      of growth response with peripheral thyroid hormone action.
AB  - OBJECTIVE: Idiopathic short stature (ISS) describes short children with normal GH
      secretion. Although GH treatment increases their heights, growth response to the
      therapy differs among patients. Thyroid hormones (TH) are essential for
      longitudinal growth acting mainly through TH receptors (TR) alpha and beta. We
      have previously reported that GH treatment reduced peripheral TH action in Turner
      Syndrome by TR down-regulation. The aims of the study were to assess the effect
      of GH treatment to ISS on peripheral TH action and the correlation between
      thyroid status and growth response to the therapy. SUBJECTS, DESIGN AND
      MEASUREMENTS: Eighteen normal (control) and twenty-five ISS children were
      enrolled and evaluated before and after 12 months of life time (control) or 12
      months of GH therapy (ISS). Fasting blood was used for serum biochemical
      evaluations, peripheral blood mononuclear cells for TR mRNA determination by QRT
      PCR and growth parameters by standard methods. RESULTS: GH treatment modified
      neither TR mRNA levels nor serum markers of TH action in ISS evaluated as a whole
      group. However, the individual change in TRbeta mRNA levels correlated to the
      change in sex hormone-binding globulin (SHBG) levels after GH therapy. The growth
      response to GH correlated positively with the change in TRalpha mRNA level and
      negatively with that in TRbeta mRNA, TSH and SHBG levels. The change in each TR
      mRNA isoform after GH treatment correlated negatively with its own basal level.
      CONCLUSIONS: GH therapy induced individual changes in TR expression in ISS that
      correlated with their growth response. The basal TR mRNA level could predetermine
      the change in TR expression and therefore the sensitivity to GH treatment.

PMID- 21091752
TI  - Lanreotide autogel-induced tumour shrinkage in thyrotropin-secreting pituitary
      macroadenomas.

PMID- 21091753
TI  - How primary care dentists perceive and are influenced by research.
AB  - INTRODUCTION: Little is understood as to how primary care dentists alter their
      clinical practice. AIM: To develop an understanding of how primary care dentists
      view and use research to inform their clinical practice. METHODS: An iterative
      approach was followed using two methods of data collection. A focus group was
      undertaken with dentists and researchers who had been involved in primary care
      dental research. Subsequently phased, qualitative interviews were undertaken with
      primary care dentists with a range of research experiences. Focus group and
      interviews were audio-recorded and transcribed verbatim. Six people participated
      in the focus group. Eighteen dentists participated in the interviews. Interviews
      were undertaken in four phases until saturation was achieved. Data were analysed
      using constant comparison. FINDINGS: Evidence-based dentistry was considered the
      ideal. However, the research base for primary care dentistry was thought to lag
      behind clinical services, to focus on incorrect endpoints, to disregard the
      patients' voice and failed to consider the impact of conducting research on
      dental practices. Dentists modified their clinical practice based upon research,
      colleagues' opinions, courses and ad hoc personal evaluation. Uptake of research
      was affected by the ethos of the practice, which determined whether the dentists
      were early or late adopters of research and financial viability of new
      interventions. CONCLUSION:   Dentists wanted concise, timely evidence-based
      guidance to aid their management of patients. Further research needs to be
      undertaken to understand how to develop an evidence-based culture in primary
      dental care.

PMID- 21091754
TI  - The association between neighborhood social capital and self-reported dentate
      status in elderly Japanese--the Ohsaki Cohort 2006 Study.
AB  - OBJECTIVES: Little is known about the influence of social capital on dental
      health. The aim of the present cross-sectional study was to determine the
      association between neighborhood social capital, individual social networks and
      social support and the number of remaining teeth in elderly Japanese. METHODS: In
      December 2006, self-administered questionnaires were sent to 31,237 eligible
      community-dwelling individuals (response rate: 73.9%). Included in the analysis
      were 21,736 participants. Five neighborhood social capital variables were
      calculated from individual civic networks, sports and hobby networks, volunteer
      networks, friendship networks and social support variables. We used multilevel
      logistic regression models to estimate the odds ratio (OR) of having 20 or more
      teeth according to neighborhood social capital variables with adjustment for sex,
      age, individual social networks and social support, educational attainment,
      neighborhood educational level, dental health behavior, smoking status, history
      of diabetes and self-rated health. RESULTS: The average age of the participants
      was 74.9 (standard deviation; 6.6) years, and 28.5% of them had 20 or more teeth.
      In the univariate multilevel model, there were statistically significant
      associations between neighborhood sports and hobby networks, friendship networks
      and self-reported dentate status. In the multivariable multilevel model, compared
      with participants living in lowest friendship network neighborhoods, those living
      in highest friendship network neighborhoods had an OR 1.17 (95% confidence
      interval, 1.04-1.30) times higher for having 20 or more teeth. CONCLUSIONS: There
      is a significant association between one network aspect of neighborhood social
      capital and individual dentate status regardless of individual social networks
      and social support.

PMID- 21091755
TI  - A longitudinal study of the relative importance of factors related to use of
      dental services among young adults.
AB  - BACKGROUND: The decline in the appropriate use of dental services from childhood
      to adulthood is of concern. The relative importance of factors influencing use of
      dental services in young adulthood should inform strategies to address this
      issue. AIM: To develop models predictive of inadequate utilisation of dental care
      in young adults and to determine the relative importance of health behaviours,
      need for dental care, and socio-demographic factors. Inadequate utilisation of
      dental care was determined as lack of visit for dental care during the study
      period and as problem-based care-seeking behavior. METHODS: A random sample of
      Adelaide young adults was selected from the electoral roll. Participants were
      interviewed and offered a dental examination at baseline. Two and a half years
      later participants were contacted again and interviewed on the use of dental
      services and usual reason for visiting and a number of explanatory factors. The
      population attributable fractions for the explanatory variables which were
      significant in the model for this cohort of young adults were calculated using
      the log-binomial method. RESULTS: There were 819 participants at follow-up a
      response rate of 65% of baseline participants. In the two and a half year period
      between baseline and follow-up about one quarter of young adults did not make a
      dental visit and over one third reported that they usually made a dental visit
      for a problem. The attributable fraction calculation indicated that 30% of
      infrequent visiting was attributed to reporting no need for dental care, 17% to
      difficulty paying a $100 dental bill, 17% to being male and 10% to smoking. The
      attributable fraction calculation indicated that 27% of usually visiting for a
      problem was attributed to having no tertiary education, 23% to not having dental
      insurance, 14% to being male, 12% to smoking, 10% to avoiding dental care due to
      cost and 5% to use of the public sector. CONCLUSION: Need and affordability
      factors were more important than general health behavior factors in influencing
      use of dental care by a cohort of young adults.

PMID- 21091756
TI  - Adding dermatoscopy to naked eye examination of equivocal melanocytic skin
      lesions: effect on intention to excise by general dermatologists.
AB  - BACKGROUND: According to the literature, dermatoscopy can improve diagnostic
      accuracy for melanoma. However, a weak point of the studies in the literature is
      that most were carried out in a 'privileged' setting of dermatologists who are
      expert in dermato-oncology, and who work in departments specializing in screening
      pigmented lesions. This study was set up to specifically evaluate whether the use
      of dermatoscopy by general dermatologists would also improve accuracy. AIM: To
      analyse the effect on intention to excise lesions (intervention yes/no) of adding
      either dermatoscopy (20 years after the advent of the method) or detailed lesion
      classification (melanoma yes/no) to clinical examination by the naked eye. More
      specifically, we evaluated whether the current practice of general dermatologists
      using dermatoscopy improves the sensitivity and specificity values, and thus the
      diagnostic accuracy. METHODS: Eight general dermatologists examined separately
      clinical images and combined (clinical and dermatoscopic) images of 200
      melanocytic lesions that had been excised (64 melanomas and 136 melanocytic
      naevi). RESULTS: Focusing on intention to excise (intervention yes/no), addition
      of dermatoscopy to naked eye examination resulted in an increase in sensitivity
      for all observers (average gain +4.5%) but an overall nonsignificant reduction in
      specificity (-4.5%, P=0.10). Diagnostic accuracy, which increased when
      examination was focused on melanoma (yes/no) classification (+4.1%, P<0.05)
      remained unchanged (-1.62%; P=0.36). CONCLUSIONS: The effect of adding
      dermatoscopy to naked eye examination of melanocytic lesions on 'general
      dermatologists' changes according to the aim of the examination. Dealing with the
      intention to excise, the increase of sensitivity associated with dermatoscopy
      (lower risk of leaving a melanoma unexcised) is obtained at the expense of
      specificity (higher number of melanocytic naevi excised) without improving
      overall diagnostic accuracy.

PMID- 21091757
TI  - Welcome to the conversation: webgaging you in discussion about current medical
      education topics.

PMID- 21091758
TI  - Feedback, the various tasks of the doctor, and the feedforward alternative.
AB  - OBJECTIVES: This study aims to alert users of feedback to its dangers, explain
      some of its complexities and offer the feedforward alternative. METHODS: We
      review the damage that feedback may cause to both motivation and performance. We
      provide an initial solution to the puzzle of the feedback sign (positive versus
      negative) using the concepts of promotion focus and prevention focus. We discuss
      additional open questions pertaining to feedback sign and consider implications
      for health care systems. RESULTS: Feedback that threatens the self is likely to
      debilitate recipients and, on average, positive and negative feedback are similar
      in their effects on performance. Positive feedback contributes to motivation and
      performance under promotion focus, but the same is true for negative feedback
      under prevention focus. We offer an alternative to feedback--the feedforward
      interview--and describe a brief protocol and suggestions on how it might be used
      in medical education. CONCLUSIONS: Feedback is a double-edged sword; its
      effective application includes careful consideration of regulatory focus and of
      threats to the self. Feedforward may be a good substitute for feedback in many
      settings.

PMID- 21091760
TI  - Second-year medical students' motivational beliefs, emotions, and achievement.
AB  - CONTEXT: A challenge for medical educators is to better understand the personal
      factors that lead to individual success in medical school and beyond. Recently,
      educational researchers in fields outside medicine have acknowledged the
      importance of motivation and emotion in students' learning and performance. These
      affective factors have received less emphasis in the medical education
      literature. OBJECTIVES: This longitudinal study examined the relations between
      medical students' motivational beliefs (task value and self-efficacy),
      achievement emotions (enjoyment, anxiety and boredom) and academic achievement.
      METHODS: Second-year medical students (n=136) completed motivational beliefs and
      achievement emotions surveys following their first and second trimesters,
      respectively. Academic achievement was operationalised as students' average
      course examination grades and national board shelf examination scores. RESULTS:
      The results largely confirmed the hypothesised relations between beliefs,
      emotions and achievement. Structural equation modelling revealed that task value
      beliefs were positively associated with course-related enjoyment (standardised
      regression coefficient [beta] = 0.59) and were negatively related to boredom
      (beta= -0.25), whereas self-efficacy beliefs were negatively associated with
      course-related anxiety only (beta = -0.47). Furthermore, student enjoyment was
      positively associated with national board shelf examination score (beta = 0.31),
      whereas anxiety and boredom were both negatively related to course examination
      grade (beta= -0.36 and -0.27, respectively). The overall structural model
      accounted for considerable variance in each of the achievement outcomes: R(2) =
      0.20 and 0.14 for the course examination grade and national board shelf
      examination score, respectively. CONCLUSIONS: This study suggests that medical
      students' motivational beliefs and achievement emotions are important
      contributors to their academic achievement. These results have implications for
      medical educators striving to understand the personal factors that influence
      learning and performance in medical training.

PMID- 21091759
TI  - Creating an ideal social and behavioural sciences curriculum for medical
      students.
AB  - OBJECTIVES: Undergraduate medical education programmes universally struggle with
      overfull curricula that make curricular changes quite challenging. Final content
      decisions are often influenced by available faculty staff, vocal champions or
      institutional culture. We present a multi-modal process for identifying 'need-to
      know' content while leveraging curricular change, using the social and
      behavioural sciences (SBS) as an exemplar. METHODS: Several multi-modal
      approaches were used to identify and triangulate core SBS curricula, including: a
      national survey of 204 faculty members who ranked the content importance of each
      of the SBS content areas; a comprehensive review of leading medical SBS
      textbooks; development of an algorithm to assess the strength of evidence for and
      potential clinical impact of each SBS construct; solicitation of student input,
      and review of guidelines from national advocacy organisations. To leverage
      curricular change, curriculum mapping was used to compare the school's 'actual'
      SBS curriculum with an 'ideal' SBS curriculum to highlight educational needs and
      areas for revision. Clinical clerkship directors assisted in translating core SBS
      content into relevant clinical competencies. RESULTS: Essential SBS content areas
      were identified along with more effective and efficient ways of teaching SBS
      within a medical setting. The triangulation of several methods to identify
      content raised confidence in the resulting content list. Mapping actual versus
      ideal SBS curricula highlighted both current strengths and weaknesses and
      identified opportunities for change. CONCLUSIONS: This multi-modal, several-stage
      process of generating need-to-know curricular content and comparing it with
      current practices helped promote curricular changes in SBS, a content area that
      has been traditionally difficult to teach and is often under-represented. It is
      likely that this process can be generalised to other emerging or under
      represented topic areas.

PMID- 21091761
TI  - Lack of association between resident doctors' well-being and medical knowledge.
AB  - OBJECTIVES: Resident doctors' (residents) well-being impacts on the medical care
      they provide. Despite the high prevalence of resident doctors' distress, the
      relationship between their well-being and the specific competencies defined by
      the Accreditation Council for Graduate Medical Education is poorly understood. We
      evaluated the association of resident well-being with medical knowledge as
      assessed on both a standardised test of general medical knowledge and at the end
      of web-based courses on a series of focused topics. METHODS: We conducted a
      repeated cross-sectional study of associations between well-being and medical
      knowledge scores over time for internal medicine residents from July 2004 to June
      2007. Well-being measures included linear analogue self-assessment (LASA) scales
      measuring quality of life (including overall quality of life, mental, physical
      and emotional well-being, and fatigue), the Medical Outcome Study Eight-Item
      Short Form Health Survey (SF-8) assessment of mental and physical well-being, the
      Maslach Burnout Inventory and the PRIME-MD two-item depression screen. We also
      measured empathy using the perspective taking and empathic concern subscales of
      the Interpersonal Reactivity Index. Medical knowledge measures included scores on
      web-based learning module post-tests and scores on the national Internal Medicine
      In-Training Examination (IM-ITE). As data for each association were available for
      at least 126 residents, this study was powered to detect a small-to-moderate
      effect size of 0.3 standard deviations. RESULTS: No statistically significant
      associations were observed between well-being and either web-based learning
      module post-test score or IM-ITE score. Parameter estimates of the association of
      well-being variables with knowledge scores were uniformly small. For all well
      being metrics, meaningful differences were associated with knowledge score
      difference estimates of < 1 percentage point. CONCLUSIONS: Resident well-being
      appears to have limited association with competence in medical knowledge as
      assessed following web-based courses on specific topics or using standardised
      general medical examinations.

PMID- 21091763
TI  - Morphology of brachial plexus and axillary artery in bonobo (Pan paniscus).
AB  - A left brachial plexus and axillary artery of bonobo (Pan paniscus) were
      examined, and the interrelation between the brachial plexus and the axillary
      artery was discussed. This is the first report of the brachial plexus and the
      axillary artery of bonobo. The bonobo brachial plexus formed very similar pattern
      to that of other ape species and human. On the other hand, the branches of the
      bonobo axillary artery had uncommon architecture in comparison with human case.
      The axillary artery did not penetrate the brachial plexus and passes through all
      way along anterior to the brachial plexus. Only 4.9% of human forelimbs have this
      pattern. Moreover, the brachial artery runs through superficially anterior to
      branches of the brachial plexus.

PMID- 21091764
TI  - Macroscopic anatomy of the lower respiratory system in a nocturnal burrowing
      rodent: African giant pouched rat (Cricetomys gambianus, Waterhouse 1840).
AB  - Cricetomys gambianus is a rat that lives principally in burrows, coming out at
      night in search of food. The design and structure of the lower respiratory system
      reflects its oxygen and metabolic demand which can be attributed to its habitat.
      A morphological and morphometric investigation of its lower respiratory system
      was undertaken to document the normal anatomical features and assess its morpho
      functional paradigm. Specifically, an anatomical detail of the lungs and
      conductive airway was described, the structures being elucidated by dissection
      and radiography. Evaluation of dissected specimens showed that tracheal
      cartilages ranged from 21 to 33 rings with an average of 25.5. They exhibited a
      random pattern of anastomoses between adjacent rings. Transverse diameters of the
      principal bronchus in the male and female rats were 3.767 and 3.759 mm
      respectively. The right lung consisted of four lobes while the left lung was not
      lobed. Bronchogram revealed that lung lobation corresponded with bronchial tree
      division. Inter-lobar fissures were absent on the right lung except for the
      ventral boarder separating the cranial lobe from the caudal lobe. The entire
      lungs provided stability to the heart in situ, through the cardiac notch. This
      study also included correlation analysis of the dimensions, weights and volumes
      of the lower respiratory organs with the nose-rump length and body weight of 18
      African giant pouched rats of both sexes. The relationship of the anatomy of the
      lower respiratory system of the rodent to the oxygen tension in their burrow and
      to their energy utilization is discussed.

PMID- 21091765
TI  - Dementia--too little, too late?

PMID- 21091766
TI  - Melatonin and vitamin D3 synergistically down-regulate Akt and MDM2 leading to
      TGFbeta-1-dependent growth inhibition of breast cancer cells.
AB  - Melatonin and vitamin D3 inhibit breast cancer cell growth and induce apoptosis,
      but they have never been combined as a breast cancer treatment. Therefore, we
      investigated whether their association could lead to an enhanced anticancer
      activity. In MCF-7 breast cancer cells, melatonin together with vitamin D3,
      induced a synergistic proliferative inhibition, with an almost complete cell
      growth arrest at 144 hr. Cell growth blockade is associated to an activation of
      the TGFbeta-1 pathway, leading to increased TGFbeta-1, Smad4 and phosphorylated
      Smad3 levels. Concomitantly, melatonin and D3, alone or in combination, caused a
      significant reduction in Akt phosphorylation and MDM2 values, with a consequent
      increase of p53/MDM2 ratio. These effects were completely suppressed by adding a
      monoclonal anti-TGFbeta-1 antibody to the culture medium. Taken together, these
      results indicate that cytostatic effects triggered by melatonin and D3 are likely
      related to a complex TGFbeta-1-dependent mechanism, involving down-regulation of
      both MDM2 and Akt-phosphorylation.

PMID- 21091767
TI  - Assessing the value of the umbrella-species concept for conservation planning
      with meta-analysis.
AB  - The umbrella-species concept, which suggests that conservation strategies
      designed for one species may benefit co-occurring species, has been promoted as a
      framework for conservation planning. Nevertheless, there has been considerable
      variation in the outcome of empirical tests of this concept that has led
      researchers to question its value, so we used data from 15 published studies in a
      meta-analysis to evaluate whether conservation of putative umbrella species also
      conserves co-occurring species. We tested the effectiveness of putative umbrella
      species categorized by taxonomic group, taxonomic similarity to co-occurring
      species, body size, generality of resource use, and trophic level to evaluate
      criteria proposed to guide the selection of umbrella species. We compared species
      richness and number of individuals (by species and higher taxonomic group)
      between sites with and without putative umbrella species to test whether more co
      occurring species were present in greater abundances when the area or resource
      needs of umbrella species were met. Species richness and abundance of co
      occurring species were consistently higher in sites where umbrella species were
      present than where they were not and for conservation schemes with avian than
      with mammalian umbrella species. There were no differences in species richness or
      species abundance with resource generalist or specialist umbrella species or
      based on taxonomic similarity of umbrella and co-occurring species. Taxonomic
      group abundance was higher in across-taxonomic umbrella species schemes than when
      umbrella species were of the same taxon as co-occurring species. Co-occurring
      species had similar, or higher, species richness with small-bodied umbrella
      species relative to larger-bodied umbrella species. The only significant
      difference among umbrella species categorized by trophic level was that species
      richness was higher with omnivorous than it was with carnivorous avian umbrella
      species. Our results suggest there is merit to the umbrella-species concept for
      conservation, but they do not support the use of the criteria we used to identify
      umbrella species.

PMID- 21091768
TI  - Assessment of the conservation efforts to prevent extinction of the Iberian lynx.
AB  - The Iberian lynx (Lynx pardinus) may be the first charismatic felid to become
      extinct in a high-income country, despite decades of study and much data that
      show extinction is highly probable. The International Union for Conservation of
      Nature categorizes it as critically endangered; about 200 free-ranging
      individuals remain in two populations in southern Spain. Conservation measures
      aimed at averting extirpation have been extensively undertaken with 4 of the
      former 10 Iberian lynx populations recorded 25 years ago. Two of the four
      populations have been extirpated. The number of individuals in the third
      population have declined by 83%, and in the fourth the probability of extirpation
      has increased from 34% to 95%. Major drivers of the pending extinction are the
      small areas to which conservation measures have been applied; lack of
      incorporation of evidence-based conservation, scientific monitoring, and adaptive
      management into conservation efforts; a lack of continuity in recovery efforts,
      and distrust by conservation agencies of scientific information. In contrast to
      situations in which conservation and economic objectives conflict, in the case of
      the Iberian lynx all stakeholders desire the species to be conserved.

PMID- 21091769
TI  - Acknowledging conservation trade-offs and embracing complexity.
AB  - There is a growing recognition that conservation often entails trade-offs. A
      focus on trade-offs can open the way to more complete consideration of the
      variety of positive and negative effects associated with conservation
      initiatives. In analyzing and working through conservation trade-offs, however,
      it is important to embrace the complexities inherent in the social context of
      conservation. In particular, it is important to recognize that the consequences
      of conservation activities are experienced, perceived, and understood differently
      from different perspectives, and that these perspectives are embedded in social
      systems and preexisting power relations. We illustrate the role of trade-offs in
      conservation and the complexities involved in understanding them with recent
      debates surrounding REDD (Reducing Emissions from Deforestation and Degradation),
      a global conservation policy designed to create incentives to reduce tropical
      deforestation. Often portrayed in terms of the multiple benefits it may provide:
      poverty alleviation, biodiversity conservation, and climate-change mitigation;
      REDD may involve substantial trade-offs. The gains of REDD may be associated with
      a reduction in incentives for industrialized countries to decrease carbon
      emissions; relocation of deforestation to places unaffected by REDD; increased
      inequality in places where people who make their livelihood from forests have
      insecure land tenure; loss of biological and cultural diversity that does not
      directly align with REDD measurement schemes; and erosion of community-based
      means of protecting forests. We believe it is important to acknowledge the
      potential trade-offs involved in conservation initiatives such as REDD and to
      examine these trade-offs in an open and integrative way that includes a variety
      of tools, methods, and points of view.

PMID- 21091770
TI  - The role of translocation in recovery of woodland caribou populations.
AB  - Maintenance of viable populations of many endangered species will require
      conservation action in perpetuity. Efforts to conserve these species are more
      likely to be successful if their reliance on conservation actions is assessed at
      the population level. Woodland caribou (Rangifer tarandus caribou) were
      extirpated recently from Banff National Park, Canada, and translocations of
      caribou to Banff and neighboring Jasper National Park are being considered. We
      used population viability analysis to assess the relative need for and benefits
      from translocation of individuals among caribou populations. We measured
      stochastic growth rates and the probability of quasi extinction of four
      populations of woodland caribou with and without translocation. We used two vital
      rates in our analysis: mean adult female survival and mean number of calves per
      breeding-age female as estimates of mean fecundity. We isolated process variance
      for each vital rate. Our results suggested the Tonquin caribou population in
      Jasper is likely to remain viable without translocation, but that translocation
      is probably insufficient to prevent eventual extirpation of the two other
      populations in Jasper. Simulated reintroductions of caribou into Banff resulted
      in a 53-98% probability of >8 females remaining after 20 years, which suggests
      translocation may be an effective recovery tool for some caribou populations.

PMID- 21091771
TI  - Integrin beta3 and its ligand regulate the expression of uPA through p38 MAPK in
      breast cancer.
AB  - Interplay between integrins and extracellular matrix is suggested to play an
      important role in malignant progression and tumor differentiation. The aim of the
      study was to determine the combined expression of integrin beta3 and tenascin-c
      (TN-c) in breast cancer and examine whether integrin beta3 and TN-c can activate
      urokinase-type plasminogen activator (uPA) through p38 mitogen-activated protein
      kinase (p38 MAPK). We detected the expression of integrin beta3, TN-c, p-p38, and
      uPA in 80 cases of breast invasive ductal carcinoma by immunohistochemistry. In
      addition, we blocked integrin beta3 and TN-c in the MDA-MB-231 breast cancer
      cells and detected the expression of p-p38 and uPA by Western blot. Integrin
      beta3, TN-c, p-p38, and uPA showed high levels of expression in breast invasive
      ductal carcinoma. The expression of integrin beta3, TN-c, and uPA was correlated
      with lymph node metastasis and TNM stage in breast cancer. Furthermore,
      correlations were noted between any two of the three proteins. The expression of
      p-p38 and uPA decreased in MDA-MB-231 cells after the addition of integrin beta3
      antibody and TN-c antibody. The expression of uPA decreased after addition of
      SB203580. Our results demonstrate that inhibition of the expression of integrin
      beta3 and TN-c could decrease the expression of uPA through p38 MAPK in breast
      cancer, suggesting that the interaction between integrin beta3 and TN-c serves an
      important role in breast cancer.

PMID- 21091772
TI  - Differential expression of MSX2 in nodular hyperplasia, high-grade prostatic
      intraepithelial neoplasia and prostate adenocarcinoma.
AB  - One of the common features in advanced prostate cancer is bone metastasis. In
      this study, we investigated the clinical relevance of a bone factor, MSX2, in
      predicting the metastatic ability of prostate adenocarcinoma. Evaluation of MSX2
      expression was performed using prostate cell lines as well as patient specimens.
      A sharp decrease in MSX2 was found in primary prostate cancer cells, 22Rv1, when
      compared with the non-malignant counterparts, followed by a gradual increase in
      more aggressive prostate cancer cell lines. Interestingly, the MSX2 protein was
      upregulated and predominantly expressed in the nucleus in aggressive prostate
      cancer cell line, C4-2b, compared with the less aggressive 22Rv1. Consistent with
      the in vitro results, MSX2 nuclear expression was significantly higher in nodular
      hyperplasia when compared with high-grade prostatic intraepithelial neoplasia
      (PIN), while MSX2 nuclear expression in prostate adenocarcinoma was higher than
      that in high-grade PIN. Importantly, MSX2 expression was increased significantly
      in tumors with metastasis compared with those without metastasis. Finally, MSX2
      nuclear scores were significantly increased in patients with preoperative serum
      PSA >20 ng/mL. No correlation between MSX2 nuclear score and Gleason score was
      found. Taken together, MSX2 may serve as a potential biomarker in predicting
      primary prostate tumors with higher metastatic capability.

PMID- 21091773
TI  - Thymic epithelial tumours in Iceland: incidence and histopathology, a population
      based study.
AB  - The objective of this study was to re-examine histologically and restage thymic
      epithelial tumours during a 25-year period and to correlate clinical and follow
      up data. We utilized centralized registries in Iceland to establish a true
      nationwide incidence rate, previously unreported. A retrospective whole
      population study was carried out by including all patients diagnosed with a
      thymic epithelial tumour in Iceland between 1 January 1984 and 30 April 2010.
      Medical records were reviewed and presenting symptoms, diagnostic procedures and
      surgical outcome tabulated. The histology of all cases was reclassified according
      to the 2004 World Health Organization classification (A-TC). The Masaoka system
      was used for tumour staging. Median follow-up was 67 months. A total of 19
      patients were identified, 11 men (58%) and 8 women, with mean age at presentation
      of 63 years (31-87 years). The age-standardized incidence rate (ASR) was 0.3 and
      0.2/100 000/year for men and women, respectively. Types B2 (n = 5) and A (n = 5)
      were the most common histological subtypes. Half of the patients had local
      symptoms, and eight were diagnosed incidentally. Of 19 patients, 11 underwent
      resection of the tumour through median sternotomy. Five-year overall survival was
      53%. All four patients with thymic carcinoma (TC) died of disease within 2 years
      of diagnosis. For the other 15 patients, no recurrences were reported. Thymic
      tumours are rare in Iceland with an ASR (w) of 0.28 per 100 000 a year. To our
      knowledge, these are the first nationwide ASR (w) figures reported. The prognosis
      for most thymic epithelial cell tumours is excellent. However, TCs have a dismal
      long-term survival.

PMID- 21091774
TI  - Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in
      hepatocellular carcinoma in Egypt.
AB  - Egypt has the highest prevalence rate of hepatitis C virus (HCV) infection in the
      world. HCV contributes to the development of about 70% of hepatocellular
      carcinoma (HCC) cases. Understanding the molecular basis of hepatocarcinogenesis
      is important for planning the therapeutic regimen for HCC patients. To clarify
      the possible role of mismatch repair (MMR) genes in HCV-related HCC, we studied
      50 HCV-related HCC specimens (28 of which were with adjacent non-cancerous
      cirrhotic liver tissue, ANCLT) and 30 specimens of chronic liver disease (CLD)
      with no evidence of HCC. All cases were examined immunohistochemically to
      demonstrate the protein expression of hMSH2 and hMLH1. Thirty-two (64%) and 35
      (70%) of the HCC cases revealed reduced expression of hMSH2 and hMLH1,
      respectively. Reduced expression of both the proteins was obtained in 26 (52%) of
      the HCC cases. The expression of hMSH2 and hMLH1 was reduced in 53.6% and 64.3%
      of ANCLT cases, respectively, with no significant difference between HCC and
      ANCLT. All 30 specimens of CLD had preserved expression of hMSH2 and hMLH1.
      Multivariate analysis showed that the reduced expression of hMSH2 or hMLH1 was
      significantly associated with higher grades of the tumor (p = 0.002 and 0.02,
      respectively).The relationships of these MMR genes with other clinicopathologic
      factors were not significant. Reduced expression of hMSH2 and hMLH1 in both HCC
      and ANCLT suggests that this event occurs at early stages of HCV-related
      hepatocarcinogenesis. Moreover, the significant association between reduced
      expression of both MMR genes and poor histologic grades of the tumor claims that
      these proteins are involved in the process of cancer progression.

PMID- 21091775
TI  - Excision repair cross-complementation group 1 (ERCC1) expression in advanced
      urothelial carcinoma patients receiving cisplatin-based chemotherapy.
AB  - Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial
      carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key
      component of the platinum-DNA repair machinery responsible for nucleotide
      excision repair. Recent reports have suggested that ERCC1 is a predictive and
      prognostic marker in solid cancers treated with platinum-based chemotherapy. We
      performed this study to determine whether or not immunohistochemical expression
      of ERCC1 can predict objective tumor response and cancer-specific survival in
      patients with advanced urothelial carcinoma treated with cisplatin-based
      chemotherapy. We performed a retrospective analysis of 89 patients with advanced
      or recurrent urothelial cancer, who had undergone treatment at Samsung Medical
      Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89
      patients with a known tumor response were available. ERCC1 expression was
      assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was
      positive in 49 patients (55%). The overall response rate after chemotherapy was
      68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were
      negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration
      of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival
      (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1
      positive patients (p = 0.03); the difference in overall survival between patients
      with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not
      statistically significant. Other than ERCC1 expression, there was no independent
      prognostic factor for PFS. These results suggest a negative contribution by
      ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with
      cisplatin-based chemotherapy.

PMID- 21091776
TI  - Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by
      heparin-binding VEGF-A in vivo.
AB  - Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF
      A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and co
      treatment with anticoagulant low-molecular-weight heparin (LMWH) are common in
      cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF-A
      is modulated by metronomic-type treatment with: (i) the LMWH dalteparin; (ii) low
      dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using
      the quantitative rat mesentery angiogenesis assay, in which angiogenesis was
      induced by intraperitoneal injection of very low doses of VEGF, dalteparin sodium
      (Fragmin((r)) ) and epirubicin (Farmorubicin((r)) ) were administered separately
      or in combination by continuous subcutaneous infusion at a constant rate for 14
      consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e.,
      doses that reflect the clinical usage of this drug, while epirubicin was given at
      the well-tolerated dosage of 0.4 mg/kg/day. While dalteparin significantly
      stimulated angiogenesis in an inversely dose-dependent manner, epirubicin did not
      significantly affect angiogenesis. However, concurrent treatment with dalteparin
      and epirubicin significantly inhibited angiogenesis. The effect of dalteparin is
      the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact
      that co-treatment with dalteparin and epirubicin significantly inhibited
      angiogenesis suggests a complex drug effect.

PMID- 21091777
TI  - Obstruction of the lung capillaries by blood platelet aggregates and leucocytes
      in sudden infant death syndrome.
AB  - Altogether 34 cases of sudden infant death were studied postmortem with
      particular emphasis on the pathological changes in the lungs. Light microscopy,
      including application of immunohistochemical methods, and transmission electron
      microscopy were used for the identification of blood platelets and white blood
      cell types in alveolar capillaries. The main findings were platelet aggregates
      and a varying number of neutrophil polymorphonuclear granulocytes in the lung
      capillaries, mixed with a smaller number of lymphocytes. The findings may be
      interpreted as an early sign of inflammation with capillary thrombosis, resulting
      in ischaemia, i.e. arrest of flow. In 21% of the cases, inflammatory cells had
      also expanded focally into alveolar spaces, creating the picture of localized
      areas of bronchopneumonia. An infant dying suddenly of a traumatic head injury
      served as a control. Neither platelets nor leucocytes were observed in the
      alveolar capillaries of this infant. In conclusion, in lungs from cases of sudden
      infant death syndrome, the alveolar capillaries are obstructed by platelet
      aggregates and leucocytes, interpreted as signs of an initial stage of lung
      inflammation with ischaemia.

PMID- 21091778
TI  - Pertussis serology: assessment of IgG anti-PT ELISA for replacement of the CHO
      cell assay.
AB  - Two types of serological assays are commonly used for the assessment of pertussis
      vaccine-induced antibodies; the Chinese hamster ovary cell (CHO cell) assay and
      the immunoglobulin G (IgG) anti pertussis toxin (PT) enzyme-linked immunosorbent
      assay (IgG anti-PT ELISA). Recently, both the techniques have been modified to
      improve performance with sera with interfering activity (CHO cell assay) or with
      heat-treated sera (IgG anti-PT ELISA). These two improved techniques were
      compared by the analysis of 100 individual serum samples from a previous clinical
      trial and 213 sera from a longitudinal serum collection from 20 Danish adults
      recently vaccinated with the Danish acellular pertussis vaccine. The comparison
      showed a significant linear correlation between the results of the two assays
      with a p-value of <0.0001 for the 100 individual samples. We, therefore, conclude
      that the improved IgG anti-PT ELISA can be used as a replacement for the often
      troublesome and time-consuming CHO cell assay for the measurement of vaccine
      induced human antibodies to PT.

PMID- 21091779
TI  - Exacerbation of Leishmania (Viannia) shawi infection in BALB/c mice after
      immunization with soluble antigen from amastigote forms.
AB  - The present study aimed to evaluate the effects of immunization with soluble
      amastigote (AmaAg) and promastigote (ProAg) antigens from Leishmania (Viannia)
      shawi on the course of infection in BALB/c mice. After immunization with AmaAg,
      the challenged group showed greater lesion size and parasite load in the skin and
      lymph nodes, associated with diminished interleukin (IL)-2, IL-4, IL-10,
      interferon (IFN)-gamma and nitrate levels in the supernatant of lymph node cell
      cultures, together with increases in transforming growth factor (TGF)-beta
      concentrations and humoral immune response. In contrast, immunization with ProAg
      led to smaller lesion size with reduced numbers of viable parasites in the skin.
      Protection was associated with increases in IL-12, IFN-gamma, TGF-beta and
      nitrates and decreases in IL-4 and IL-10 levels. Concerning humoral immune
      response, a significant reduction in anti-leishmania immunoglobulin G was
      verified in the ProAg-challenged group. Analysis of these results suggests that
      AmaAg induced a suppressive cellular immune response in mice, favouring the
      spread of infection, whereas ProAg induced partial protection associated with
      increased cellular immune response.

PMID- 21091780
TI  - Effect of duramycin on chloride transport and intracellular calcium concentration
      in cystic fibrosis and non-cystic fibrosis epithelia.
AB  - The lantibiotic duramycin (Moli1901, Lancovutide) has been suggested as a drug of
      choice in the treatment for cystic fibrosis (CF). It has been proposed that
      duramycin may stimulate chloride secretion through Ca2(+) -activated Cl- channels
      (CaCC). We investigated whether duramycin exhibited any effect on Cl- efflux and
      intracellular Ca2(+) concentration ([Ca2(+)](i)) in CF and non-CF epithelial
      cells. Duramycin did stimulate Cl- efflux from CF bronchial epithelial cells
      (CFBE) in a narrow concentration range (around 1 MUM). However, 100 and 250 MUM
      of duramycin inhibited Cl- efflux from CFBE cells. An inhibitor of the CF
      transmembrane conductance regulator (CFTR(inh)-172) and a blocker of the
      capacitative Ca2(+) entry, gadolinium chloride, inhibited the duramycin-induced
      Cl- efflux. No effect on Cl- efflux was observed in non-CF human bronchial
      epithelial cells (16HBE), human airway submucosal gland cell line, human
      pancreatic epithelial cells, CF airway submucosal gland epithelial cells, and CF
      pancreatic cells. The [Ca2(+)](i) was increased by 3 MUM duramycin in 16HBE
      cells, but decreased after 1, and 3 MUM of duramycin in CFBE cells. The results
      suggest that the mechanism responsible for the stimulation of Cl- efflux by
      duramycin is mainly related to unspecific changes of the cell membrane or its
      components rather than to effects on CaCC.

PMID- 21091781
TI  - Comparison of IgG avidity assays in the confirmation of the diagnosis of
      cytomegalovirus primary infection.
AB  - We have compared three ELISA techniques and one chemiluminescence immunoassay
      technique for determining cytomegalovirus (CMV) immunoglobulin G (IgG) avidity in
      serum samples from patients with recent and past CMV infections. Sensitivity
      varied from 84.6% to 100%; and specificity from 78.6% to 100%. IgG avidity assays
      appear to be adequate additional tools for characterizing CMV infections.

PMID- 21091782
TI  - Fusobacterium necrophorum- detection and identification on a selective agar.
AB  - Within the last decade, Fusobacterium necrophorum subsp. funduliforme has been
      considered a clinically important pathogen causing pharyngitis especially in
      adolescents and young adults. F. necrophorum pharyngitis can progress into
      Lemierre's syndrome, which is a severe and life-threatening infection. However,
      throat swabs are not cultured anaerobically in the routine and even if cultured
      anaerobically, it can be difficult to identify F. necrophorum from the normal
      flora of the throat. F. necrophorum is therefore often overlooked as the cause of
      pharyngitis. In our laboratory, a F. necrophorum selective agar has been
      developed containing vancomycin and nalidixin, which inhibit the growth of most
      Gram-positive and many Gram-negative bacteria, respectively. beta-haemolysis of
      horse blood can be detected, which further facilitates the detection and
      identification of F. necrophorum. The F. necrophorum selective agar was evaluated
      against a quantitative real-time polymerase chain reaction assay and shown to
      have a significantly higher sensitivity for detecting F. necrophorum than the
      anaerobic agar commonly used in Denmark. Furthermore, the F. necrophorum
      selective agar does not require experienced laboratory technicians, require fewer
      subcultures, is probably less expensive and is faster to perform than other
      culture methods.

PMID- 21091783
TI  - Differential susceptibility to lethal endotoxaemia in mice deficient in IL
      1alpha, IL-1beta or IL-1 receptor type I.
AB  - The role of intereukin-1 (IL-1) in mortality caused by endotoxaemia remains
      controversial. While IL-1 receptor antagonist (IL-1Ra) protects mice from lethal
      endotoxaemia, mice deficient in IL-1beta (IL-1beta-( /)-) display normal
      susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify
      the source of these discrepancies. Mice deficient in IL-1alpha, IL-1beta or IL-1R
      type I were injected intraperitoneally with Escherichia coli or Salmonella
      typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild
      type mice. In addition, serum cytokine concentrations were determined after LPS
      challenge and in vitro cytokine production by peritoneal macrophages was
      analysed. Clearance of radioactive IL-1alpha was examined in IL-1alpha-(/)- and
      wild-type mice. IL-1beta-(/)- mice were normally susceptible to endotoxaemia and
      cytokine production did not differ from that in control mice. Surprisingly, LPS
      mortality in IL-1alpha-(/)- mice was significantly greater than that in control
      mice, accompanied by higher interferon-gamma release. These effects were mediated
      by a distorted homeostasis of IL-1RI receptors, as shown by a strongly delayed
      clearance of IL-1alpha. In contrast to the IL-1alpha-(/)- and IL-1beta-(/)- mice,
      IL-1RI-(/)- mice were completely resistant to high doses of LPS. In conclusion,
      IL-1RI-mediated signals are crucial in mediating mortality occurring as a result
      of lethal endotoxaemia. Investigation of IL-1-mediated pathways in IL-1 knock-out
      mice is complicated by a distorted homeostasis of IL-1Rs.

PMID- 21091784
TI  - Minimal erythema dose and minimal melanogenesis dose relate better to objectively
      measured skin type than to Fitzpatricks skin type.
AB  - BACKGROUND: Fitzpatrick skin type (FST I-IV) is a subjective expression of
      ultraviolet (UV) sensitivity based on erythema and tanning reactivity after a
      single exposure. Pigment protection factor (PPF) is an objective measurement of
      skin sensitivity in all skin types after a single exposure. METHODS: The aim was
      to compare FST and PPF with clinically determined minimal erythema dose (MED) and
      minimal melanogenesis dose (MMD) in 84 persons with skin types I-V both after
      single and multiple exposures (one, four, five, six, or 12) to buttock and back
      skin. RESULTS: FST was better correlated to MED than to MMD, and FST correlated
      better to constitutive than to facultative pigmented areas after multiple
      exposures rather than to a single exposure. PPF was generally much better
      correlated to MED and MMD than FST especially after a single exposure and
      multiple exposures with steady-state pigmentation. Multiple regression analyses
      showed that MED was the only significant, or most important determinator, of both
      FST and PPF. The correlation coefficient was highly significant for PPF (r2 =82).
      CONCLUSIONS: PPF is a better predictor of the individual UV sensitivity (linear
      relation) than FST (only 4 grades) and PPF can substitute FST.

PMID- 21091785
TI  - Fluorescence diagnostic imaging in patients with acne.
AB  - BACKGROUND: Orange-red fluorescence in the follicle openings, induced by
      ultraviolet A light, originates from porphyrins, the metabolic products of
      Propionibacteria acnes. PURPOSE: To investigate the relationship of orange-red
      follicular fluorescence with the severity of acne and the amount of sebum
      secretion. METHODS: Twenty-five volunteers were included. The severity of acne
      was rated on a 4-point scale. The casual sebum level was measured using a
      Sebumeter and the follicular fluorescence was determined using the camera
      Visiopor. RESULTS: Casual sebum level and the intensity of fluorescence
      (percentage of the area and number of orange-red spots) were higher at the T zone
      than at the U zone in all patients regardless of their skin type. Sebum amount
      and area of fluorescence spots were significantly negative in correlation with
      the clinical grade of acne. There was a significant positive correlation between
      the orange-red fluorescence and the casual sebum level. CONCLUSION: The orange
      red fluorescence showed stronger correlation with the presence of non
      inflammatory acne lesions (comedones) and high sebum amount than the presence of
      inflammatory acne lesions (pustules) and low sebum amount. The fluorescence
      diagnostic imaging could be useful in the objective evaluation and monitoring of
      treatment efficacy in subjects with acne-prone skin and patients with acne.

PMID- 21091786
TI  - Engineering of cotton fabrics for maximizing in vitro ultraviolet radiation
      protection.
AB  - INTRODUCTION: Cotton fabrics used in summer do not often provide good protection
      against solar ultraviolet (UV) radiation. Heavy cotton fabrics can provide good
      protection against UV radiation. However, heavy fabrics are not good from a
      comfort point of view as the air permeability and moisture vapour transmission
      rate is very low. OBJECTIVES: To engineer cotton fabrics which will provide
      maximum UV protection without sacrificing the minimum requirement of air
      permeability and thermal resistance for a particular climatic condition. METHODS:
      Sixteen plain and sixteen twill woven fabrics were manufactured using different
      cotton yarn count and picks per cm. Nonlinear regression models were developed to
      relate the fabric parameters with the ultraviolet protection factor (UPF), air
      permeability and thermal resistance. Optimization problems were formulated for
      UPF maximization keeping air permeability and thermal resistance as constraints.
      Optimization problems were solved to find out the values of yarn count and picks
      per cm. New fabrics were then woven using optimized combinations of yarn count
      and picks per cm, and error assessment between the target and the achieved fabric
      properties was performed. RESULTS: The target, optimized and achieved fabric
      properties are showing good association. When air permeability requirement is
      high, the engineered cotton fabric can provide good UV protection (UPF > 15).
      When the air permeability requirement is low, the engineered cotton fabric can
      provide excellent UV protection (UPF > 40). CONCLUSIONS: It is possible to
      engineer cotton fabrics to maximize the UV protection without compromising with
      the comfort properties.

PMID- 21091787
TI  - Fluorescence diagnosis in actinic keratosis and squamous cell carcinoma.
AB  - BACKGROUND: As different tissue types have distinct capabilities to accumulate
      protoporphyrin IX, fluorescence diagnosis with aminolevulinic acid-induced
      porphyrins (FDAP) could be used to discriminate between different types of
      tissue. Previous results demonstrated higher fluorescence ratios in squamous cell
      carcinoma (SCC) compared with actinic keratoses (AKs). OBJECTIVES: The lesional :
      non-lesional fluorescence ratio of AKs was compared with the ratio of SCC. Other
      factors influencing macroscopic fluorescence were also assessed, including
      stratum corneum thickness, which has been demonstrated to account for
      heterogeneous fluorescence in psoriasis and in AKs. METHODS: After 1 week of
      keratolytic pretreatment, FDAP was performed in 13 patients with 36 lesions
      suspected for AK or SCC. Biopsies were taken for histopathological diagnosis and
      measurement of stratum corneum thickness. RESULTS: No significant differences
      were found in the fluorescence ratio (lesional : non-lesional skin) between AKs
      and SCCs, although macroscopic fluorescence was significantly higher in Bowen's
      disease and micro-invasive SCCs. CONCLUSIONS: There could be a potential
      applicability of FDAP to differentiate premalignant lesions with a tendency to
      progress into SCC and squamous cutaneous lesions already progressing into early
      invasive cancer from other squamous cutaneous (pre)malignancies. The amount of
      hyperkeratosis, invasiveness and degree of differentiation seem to be responsible
      for variations in fluorescence intensity.

PMID- 21091788
TI  - Urocanic acid suppresses induction of immunity in human skin.
AB  - BACKGROUND/PURPOSE: Trans-urocanic acid is isomerized to cis-urocanic acid (C
      UCA) by ultraviolet radiation. C-UCA suppresses immunity in vitro and in vivo in
      animals; its effect on human skin is unknown. We sought to determine whether its
      topical application to normal skin suppresses induction of immunity to
      dinitrochlorobenzene (DNCB). METHODS: Forty subjects applied C-UCA (0%, 0.02%,
      0.2%, or 2%) for 17 days. A 40-mcg dose of DNCB was then applied to induce
      immunity. Subjects were challenged for immunity at 6-week follow-up by occluding
      doses of DNCB (0, 3.125, 6.25, or 12.5 mcg) on untreated normal skin. Induced
      immunity was measured by area of erythema and induration 2 and 4 days
      postchallenge. RESULTS: No significant differences were found in incidence of
      sensitization by C-UCA concentration (P=.59). DNCB sensitization developed in all
      10 subjects induced through 0% C-UCA (placebo); only 23 of 30 patients were
      sensitized through skin treated with C-UCA. Mean areas of erythema and induration
      induced through C-UCA-treated skin were less than those in controls (P < 0.05).
      The number of Langerhans cells in C-UCA-treated skin was unaffected. Laboratory
      tests of immune function and lymphocyte numbers were unchanged. CONCLUSION:
      Topically applied C-UCA blunts normal induction responses to a cutaneous
      sensitizer.

PMID- 21091789
TI  - Cell-density-dependent changes in mitochondrial membrane potential and reactive
      oxygen species production in human skin cells post sunlight exposure.
AB  - BACKGROUND: Solar ultraviolet radiation (UVR) is the principal etiological factor
      in skin carcinogenesis. In vivo and in vitro studies have demonstrated previously
      that oxidative DNA damage, mitochondrial mass and mitochondrial membrane
      potential (MMP) changes are associated with skin cell response to UVR stress.
      METHODS: Spontaneously immortalized human skin keratinocytes were irradiated with
      increasing sub-lethal doses of simulated sunlight irradiation (SSI) using a Q-Sun
      solar simulator. The effects of SSI on reactive oxygen species (ROS) formation,
      mitochondrial mass and MMP were then determined. RESULTS: SSI induced
      mitochondrial mass increase post low SSI (0.25-2.5 J/cm2), whereas higher SSI
      doses (5.0 and 7.5 J/cm2) decreased mitochondrial mass. Mitochondrial mass
      increased with time post 5.0 J/cm2 irradiation and all changes in mass were
      independent of cell density status. Changes in ROS and MMP were cell density
      dependent. Additionally, an inverted dose-dependent decrease in ROS formation was
      observed 3 h post SSI with the lower SSI dose (0.25 J/cm2). CONCLUSIONS:
      Observations from the present study suggest that changes in the cell's
      microenvironment (modeled through varying cell density) influence changes in MMP
      and ROS detoxifying responses in sun-exposed skin cells.

PMID- 21091790
TI  - Proteome analysis of ultraviolet-B-induced protein expression in vitro human
      dermal fibroblasts.
AB  - BACKGROUND: Ultraviolet-B (UVB) radiation can result in acute photodamage,
      photoaging and skin cancer through the induction of reactive oxygen species, DNA
      damage, activation of signaling pathways, and regulation of gene expression. In
      this study, we investigated UVB-induced alterations in protein expression in
      human dermal fibroblasts. METHODS: Skin fibroblasts were irradiated with 100
      mJ/cm2 UVB, and cell viability was monitored by the 3-(4,5)-dimethylthiahiazo(-z
      y1)-3,5-diphenytetrazoliumromide assay. Two-dimensional gel electrophoresis and
      matrix-assisted laser desorption/ionization time of flight mass spectroscopy were
      used to identify differentially expressed proteins. The mRNA and levels of
      identified proteins were detected using a quantitative real-time polymerase chain
      reaction assay and Western blot. RESULTS: UVB decreased the viability of skin
      fibroblasts. In UVB-treated cells, eighteen differentially expressed proteins
      were identified. Among these proteins, the amounts of receptor-interacting
      protein (RIP) and vimentin were significantly up-regulated. However, their mRNA
      levels decreased and remained relatively stable, respectively. CONCLUSIONS: The
      differential expression of RIP and vimentin was validated in UVB-irradiated
      fibroblasts. RIP may promote cell injury, and vimentin may contribute to the
      resistance of cells to UVB-induced damage.

PMID- 21091791
TI  - An evaluation of ultraviolet A protection and photo-stability of sunscreens
      marketed in Australia and New Zealand.

PMID- 21091792
TI  - The effect of different implant neck configurations on soft and hard tissue
      healing: a randomized-controlled clinical trial.
AB  - OBJECTIVE: to compare the soft and hard tissue healing and remodeling around
      tissue-level implants with different neck configurations after at least 1 year of
      functional loading. MATERIAL AND METHODS: eighteen patients with multiple missing
      teeth in the posterior area received two implants inserted in the same sextant.
      One test (T) implant with a 1.8 mm turned neck and one control (C) implant with a
      2.8 mm turned neck were randomly assigned. All implants were placed
      transmucosally to the same sink depth of approximately 1.8 mm. Peri-apical
      radiographs were obtained using the paralleling technique and digitized. Two
      investigators blinded to the implant type-evaluated soft and hard tissue
      conditions at baseline, 6 months and 1 year after loading. RESULTS: the mean
      crestal bone levels and soft tissue parameters were not significantly different
      between T and C implants at all time points. However, T implants displayed
      significantly less crestal bone loss than C implants after 1 year. Moreover, a
      frequency analysis revealed a higher percentage (50%) of T implants with crestal
      bone levels 1-2 mm below the implant shoulder compared with C implants (5.6%) 1
      year after loading. CONCLUSION: implants with a reduced height turned neck of 1.8
      mm may, indeed, lower the crestal bone resorption and hence, may maintain higher
      crestal bone levels than do implants with a 2.8 mm turned neck, when sunk to the
      same depth. Moreover, several factors other than the vertical positioning of the
      moderately rough SLA surface may influence crestal bone levels after 1 year of
      function.

PMID- 21091793
TI  - Decision making in the management of benign prostatic enlargement and the role of
      transabdominal ultrasound.
AB  - Benign prostate enlargement (BPE) is a common disease affecting elderly men. It
      can present clinically in many ways including, but not exclusively, lower urinary
      tract symptoms (LUTS) and acute urinary retention (AUR). Therefore, in managing
      men with BPE, a correct diagnosis in the outpatient setting is important.
      Diagnosis of BPE in the clinic can be aided by simple, non-invasive,
      transabdominal ultrasound (TAUS). In our practice, a normal prostate is generally
      defined as less than 20 mL, and shows no intravesical prostatic protrusion (IPP)
      to distort the normal funneling bladder neck on TAUS, with a maximum flow rate of
      more than 15 mL/s. The degree of IPP can be measured non-invasively in the
      midsagittal plane, and can be graded accordingly. Studies have shown that the
      grade of IPP correlates well with the degree of bladder outlet obstruction (BOO).
      In addition, TAUS can also be used to measure prostate volume (PV) and post-void
      residual urine (PVR). There is a good correlation between IPP and PV, but IPP is
      a better predictor for BOO. Patients with low-grade IPP, no significant PVR (<100
      mL) and no bothersome symptoms (low stage) can generally be watched; whereas
      those with high-grade IPP, significant PVR (>100 mL) and bothersome symptoms
      (higher stage) will need more aggressive management. The final decision for
      management can then be tailored and individualized to achieve cost-effectiveness.

PMID- 21091794
TI  - Editorial comment to outcome of different post-orchiectomy management for stage I
      seminoma: Japanese multi-institutional study including 425 patients.

PMID- 21091795
TI  - Editorial comment to carvedilol protects tubular epithelial cells from ischemia
      reperfusion injury by inhibiting oxidative stress.

PMID- 21091796
TI  - Calcium oxalate crystal deposition in metabolic syndrome model rat kidneys.
AB  - OBJECTIVE: Although an epidemiological link between the metabolic syndrome and
      kidney stone formation has been reported, the mechanism by which metabolic
      syndrome promotes kidney stone formation has yet to be elucidated. We
      investigated calcium oxalate (CaOx) kidney stone formation in a rat metabolic
      syndrome model. METHODS: We induced hyperoxaluria in 8-week-old male Otsuka Long
      Evans Tokushima fatty (OLETF) rats, and a control strain, Long-Evans Tokushima
      Otsuka (LETO) rats, by administering 1.0% ethylene glycol (EG) as their drinking
      water for 2 weeks. Rats were divided into four groups: LETO-C (control, n = 7);
      LETO-SF (stone forming, n = 8); OLETF-C (n = 7); and OLETF-SF (n = 8). Urine and
      blood samples were collected for biochemistry testing, and the kidneys were
      harvested for estimation of crystal deposition and determinations of the
      expression of osteopontin (OPN) and monocyte chemoattractant protein-1 (MCP-1).
      RESULTS: Administration of EG induced hyperoxaluria to the same degree in both
      strains. The OLETF-SF group showed a higher grade of renal crystal deposition and
      significantly higher renal calcium content than the LETO-SF group. Although the
      OLETF-C group excreted significantly higher amounts of uric acid and more acidic
      urine than the LETO-C group, similar differences were not observed in rats given
      EG. Significant upregulation of both OPN and MCP-1 was seen in the kidneys of
      hyperoxaluric rats, with higher levels of expression in the OLETF-SF group than
      the LETO-SF group. CONCLUSIONS: The present results show for the first time that
      OLETF rats form more renal CaOx crystal deposits compared with control rats under
      EG-induced hyperoxaluric conditions. The model described here should be useful
      for investigating the mechanisms by which the metabolic syndrome promotes CaOx
      kidney stone formation.

PMID- 21091797
TI  - Case of IgG4-related retroperitoneal fibrosis with concomitant rheumatoid
      arthritis.

PMID- 21091798
TI  - Profilin 1 overexpression in renal cell carcinoma.
AB  - OBJECTIVES: To gain information about overexpressed antigens in renal cell
      carcinoma (RCC) by using a chemical proteomics approach. METHODS: RCC cell line
      769P was cultured and proteome analysis was subsequently carried out in the
      culture supernatants. By using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and tandem mass spectrometry (LC-MS/MS), proteins in
      the culture supernatants were searched. A MEDLINE search to define the functions
      of the identified proteins was carried out. RESULTS: Four differentially
      regulated proteins (profilin 1, amyloid beta A4 protein [APP], proprotein
      convertase subtilisin/kexin type 1 inhibitor [ProSAAS], galectin-3-binding
      protein [LGALS3BP]) were selected. These were not overexpressed in normal kidney
      tissue or reported in RCC. Their levels were measured through western blotting of
      normal kidney and RCC tissues. No differences were observed in the expression
      levels of APP, ProSAAS or LGALS3BP between RCC and normal kidney tissues.
      Profilin 1 was overexpressed in RCC tissue. On the basis of this observation, an
      immunohistochemical analysis of profilin 1 in normal kidney and RCC tissues was
      carried out. In normal tissues, tubules that were sources of RCC stained positive
      for profilin 1. In RCC tissue, in contrast, the stromal cells in the tumors
      stained positive. CONCLUSIONS: Profilin 1 can be a key element in the
      pathological processes of RCC, such as tumorigenesis and/or tumor growth. Thus,
      it has the potential to serve as a diagnostic or progression biomarker and
      therapeutic target in RCC.

PMID- 21091799
TI  - Bacillus Calmette-Guerin treatment of non-muscle invasive bladder cancer.
AB  - Bacillus Calmette-Guerin (BCG) has been used in the intravesical treatment of non
      muscle invasive bladder cancer (NMIBC) for nearly 35 years; however, its use is
      still subject to controversy. The objective of this paper is to review the role
      of BCG in the treatment of patients with NMIBC. Clinical trials, meta-analyses
      and guidelines related to the administration, safety and efficacy of intravesical
      BCG were reviewed. Intravesical BCG is more effective than intravesical
      chemotherapy in decreasing the risk of recurrence and progression to muscle
      invasive disease; however, it is associated with more local and systemic side
      effects. It is the gold standard in patients at high risk of progression.
      Maintenance BCG is required in order to achieve the best therapeutic results;
      however, the optimal dose, induction and maintenance schedules, and duration of
      treatment are unknown and might be different for each patient. Patients failing
      BCG treatment have a poor prognosis, and cystectomy is then the recommended
      treatment. Patients at low risk of recurrence and progression should not receive
      BCG, because of its side effects. Intermediate-risk patients might be treated
      with either intravesical chemotherapy or BCG; however, for patients at high risk
      of progression, BCG is recognized as the treatment of choice. Further research is
      urgently needed to identify markers associated with BCG failure and to develop
      effective alternatives to cystectomy in patients failing BCG.

PMID- 21091800
TI  - Gender-related differences in cytochrome P450 in porcine liver--implication for
      activity, expression and inhibition by testicular steroids.
AB  - In pigs, the hepatic cytochrome P450 (CYP) 1A2, 2A and 2E1 activity is important
      in the regulation of skatole accumulation in adipose tissue. This study
      investigated gender-related differences in CYP1A2, 2A and 2E1 dependent activity,
      protein and mRNA expression. This study also investigated the gonadal steroid
      dependent inhibition of CYP activity in relation to gender and dietary
      composition. Microsomes were prepared from the liver of female and entire male
      pigs (Landrace * Yorkshire sire and Duroc boars) reared under similar conditions
      and slaughtered at an age of 164 days. A group of entire male pigs fed dried
      chicory root for 16 days prior to slaughter were included in the study. CYP
      activities were assessed by the use of probe substrates, whilst mRNA and protein
      expression were analysed by RT-PCR and Western blotting. Furthermore inhibition
      of CYP dependent activity by gonadal steroids was assessed in vitro. Microsomes
      from female pigs had greater CYP1A2 and 2A activity, as well as mRNA expression
      compared to entire male pigs. The antibodies used did not detected differences in
      protein expression. In vitro inhibition by 17beta-oestradiol, oestrone,
      androstenone and 3beta-OH androstenol of CYP2E1 activity in microsomes from
      entire male pigs as well as inhibition of CYP1A activity in chicory fed entire
      male pigs was observed. Apart from that no effect of steroids was shown. In
      conclusion, female pigs show greater CYP activity and mRNA expression. Including
      chicory in the diet for 16 days changed the gonadal steroid dependent inhibition
      of CYP activity in entire male pigs.

PMID- 21091801
TI  - Presynaptic muscarinic receptor subtypes involved in the enhancement of
      spontaneous GABAergic postsynaptic currents in hippocampal neurons.
AB  - We investigated the effects of muscarinic acetylcholine receptor (mAChR)
      activation on GABAergic synaptic transmission in rat hippocampal neurons. Current
      clamp recordings revealed that methacholine produced membrane depolarization and
      action potential firing. Methacholine augmented the bicuculline-sensitive and
      GABA(A) -mediated frequency of spontaneous inhibitory postsynaptic currents
      (sIPSCs); the action of methacholine had a slow onset and longer duration. The
      increase in methacholine-evoked sIPSCs was completely inhibited by atropine and
      was insensitive to glutamatergic receptor blockers. Interestingly, methacholine
      action was not inhibited by intracellular perfusion with GDP-beta-S, suggesting
      that muscarinic effects on membrane excitability and sIPSC frequency are mainly
      presynaptic. McN-A-343 and pirenzepine, selective agonist and antagonist of the
      m1 mAChR subtype, respectively, neither enhanced sIPSCs nor inhibited the
      methacholine effect. However, the m3-m5 mAChR antagonist 4-DAMP, and the m2-m4
      mAChR antagonist himbacine inhibited the methacholine effect. U73122, an IP(3)
      production inhibitor, and 2APB, an IP(3) receptor blocker, drastically decreased
      the methacholine effect. Recording of miniature events revealed that besides the
      effect exerted by methacholine on membrane firing properties and sIPSC frequency,
      muscarinic receptors also enhanced the frequency of mIPSCs with no effect on
      their amplitude, possibly modulating the molecular machinery subserving vesicle
      docking and fusion and suggesting a tight colocalization at the active zone of
      the presynaptic terminals. These data strongly suggest that by activating
      presynaptic m2, m3, m4 and m5 mAChRs, methacholine can increase membrane
      excitability and enhance efficiency in the GABA release machinery, perhaps
      through a mechanism involving the release of calcium from the endoplasmic
      reticulum.

PMID- 21091803
TI  - Mechanisms underlying the representation of angles embedded within contour
      stimuli in area V2 of macaque monkeys.
AB  - We previously found that surprisingly many V2 neurons showed selective responses
      to particular angles embedded within continuous contours [M. Ito & H. Komatsu
      (2004)Journal of Neuroscience, 24, 3313-3324]. Here, we addressed whether the
      selectivity is dependent on the presence of individual constituent components or
      on the unique combination of these components. To reveal roles of constituent
      half-lines in response to whole angles, we conducted a quantitative model study
      after the framework of cascade models. Our linear-non-linear summation model
      implemented a few subunits selective to particular half-lines and was fitted to
      neuronal responses for each neuron. The study indicates that the best-fitting
      models well replicate the selectivity in the majority of V2 neurons and that the
      angle selectivity is dependent on a linear combination of responses to individual
      half-line components of the angles. The implication is that optimal angles are
      given by a combination of two preferred half-line components and the selectivity
      is sharpened by introducing suppression to non-preferred half-line components,
      rather than a specific facilitatory interaction between two preferred half-line
      components. The study indicates the participation of the gain control of
      responsiveness according to the number of half-line components. We also showed
      that the selectivity to acute angles depends on a combination of responses to one
      preferred component and weak responses to another component. Therefore, we
      concluded that the angle selectivity is dependent on selective responses to
      individual half-line components of the angles rather than a unique combination
      between them, whereas neurons could be selective to various angle widths at area
      V2.

PMID- 21091802
TI  - Light-evoked synaptic activity of retinal ganglion and amacrine cells is
      regulated in developing mouse retina.
AB  - Recent studies have shown a continued maturation of visual responsiveness and
      synaptic activity of retina after eye opening, including the size of receptive
      fields of retinal ganglion cells (RGCs), light-evoked synaptic output of RGCs,
      bipolar cell spontaneous synaptic inputs to RGCs, and the synaptic connections
      between RGCs and ON and OFF bipolar cells. Light deprivation retarded some of
      these age-dependent changes. However, many other functional and morphological
      features of RGCs are not sensitive to visual experience. To determine whether
      light-evoked synaptic responses of RGCs undergo developmental change, we directly
      examined the light-evoked synaptic inputs from ON and OFF synaptic pathways to
      RGCs in developing retinas, and found that both light-evoked excitatory and
      inhibitory synaptic currents decreased, but not increased, with age. We also
      examined the light-evoked synaptic inputs from ON and OFF synaptic pathways to
      amacrine cells in developing retinas and found that the light-evoked synaptic
      input of amacrine cells is also downregulated in developing mouse retina.
      Different from the developmental changes of RGC spontaneous synaptic activity,
      dark rearing has little effect on the developmental changes of light-evoked
      synaptic activity of both RGCs and amacrine cells. Therefore, we concluded that
      the synaptic mechanisms mediating spontaneous and light-evoked synaptic activity
      of RGCs and amacrine cells are likely to be different.

PMID- 21091804
TI  - Neuromuscular recruitment related to stimulus presentation and task instruction
      during the anti-saccade task.
AB  - The contextual control of movement requires the transformation of sensory
      information into appropriate actions, guided by task-appropriate rules. Previous
      conceptualizations of the sensorimotor transformations underlying anti-saccades
      (look away from a stimulus) have suggested that stimulus location is first
      registered and subsequently transformed into its mirror location before being
      relayed to the motor periphery. Here, by recording neck muscle activity in
      monkeys performing anti-saccades, we demonstrate that stimulus presentation
      induces a transient recruitment of the neck muscle synergy used to turn the head
      in the wrong direction, even though subjects subsequently looked away from the
      stimulus correctly. Such stimulus-driven aspects of recruitment developed
      essentially at reflexive latencies (~60-70 ms after stimulus presentation), and
      persisted at modest eccentricities regardless of head-restraint. Prior to
      stimulus presentation, neck muscle activity also reflected whether the animals
      were preparing for an anti-saccade or a pro-saccade (look toward a stimulus).
      Neck muscle activity prior to erroneous anti-saccades also resembled that
      observed prior to pro-saccades. These results emphasize a parallel nature to the
      sensorimotor transformations underlying the anti-saccade task, suggesting that
      the top-down and bottom-up processes engaged in this task influence the motor
      periphery. The bottom-up aspects of neck muscle recruitment also fit within the
      context of recent results from the limb-movement literature, showing that
      stimulus-driven activation of muscle synergies may be a generalizing strategy in
      inertial-laden systems.

PMID- 21091806
TI  - Drug-drug interactions that reduce the formation of pharmacologically active
      metabolites: a poorly understood problem in clinical practice.
AB  - Drug-drug interactions can lead to reduced efficacy of medical treatment.
      Therapeutic failure may for instance result from combined treatment with an
      inhibitor of the specific pathway that is responsible for the generation of
      pharmacologically active drug metabolites. This problem may be overlooked in
      clinical practice. Several examples of drugs will be discussed -clopidogrel,
      losartan, tamoxifen and codeine - to illustrate differences in the potential
      impact on drug treatment in clinical practice. We conclude that the combined use
      of cytochrome P450-blocking serotonin reuptake inhibitors and tamoxifen or
      codeine should be avoided, whereas the situation is much more complex regarding
      the use of proton pump inhibitors together with clopidogrel, and the evidence
      regarding cytochrome P450 inhibitor-dependent activation of losartan is
      inconclusive.

PMID- 21091805
TI  - Urges for food and money spill over into motor system excitability before action
      is taken.
AB  - Much human behavior is driven by urges. Yet research into urges is hampered by a
      paucity of tools to objectively index their strength, timing and control. Here we
      used transcranial magnetic stimulation (TMS) and concurrent electromyography to
      examine whether urges for food and money are detectable via motor system
      excitability. In Experiment 1, we used a naturalistic food paradigm to show that
      food items that were most strongly wanted elicited the largest motor
      excitability, even before participants knew which response to make to get them.
      In Experiment 2a, we replicated the results using money - motor excitability was
      greater for larger monetary amounts. In Experiment 2b we show that monetary
      amount does not modulate motor excitability when participants simply observe,
      without having to take action. As the chief effect occurred prior to the subject
      knowing which motor response to make, it is not merely related to response
      preparation, and as the effect was present only when action was required, it is
      not merely related to increased arousal. Instead, the increased motor
      excitability likely indexes the degree of motivation a subject has to perform an
      action. Thus, we have used TMS to demonstrate that urges for food and money
      'spill over' into the motor system. This is likely mediated by interactions
      between the limbic system (including the orbital frontal cortex) and the motor
      system, probably at the level of the basal ganglia. Implications are discussed
      for theories of embodied cognition and for methodological progress in studying
      urge control.

PMID- 21091807
TI  - Apolipoprotein B (apoB) more closely related to subclinical atherosclerosis than
      non-HDL cholesterol and LDL cholesterol.

PMID- 21091808
TI  - Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying
      individuals at increased cardiovascular risk.
AB  - BACKGROUND: To compare apolipoprotein B (apoB), non-high-density lipoprotein
      cholesterol (non-HDL-c) and low-density lipoprotein-cholesterol (LDL-c) for
      identifying individuals with a deteriorated cardiovascular (CV) risk profile,
      including a panel of subclinical atherosclerosis measurements and prevalent
      cardiovascular disease (CVD) in a Dutch population-based cohort. METHODS:
      Clinical and biochemical measurements and a panel of noninvasive parameters of
      subclinical atherosclerosis were determined in 1517 individuals, aged 50-70
      years. RESULTS: Both men and women with increasing levels of apoB and non-HDL-c
      were more obese, had higher blood pressure and fasting glucose levels, and a more
      atherogenic lipid profile. Furthermore, compared to the reference group (composed
      of those with apoB, non-HDL-c and LDL-c levels in the bottom quartiles),
      participants with high apoB and high non-HDL-c levels had a lower ankle-brachial
      index at rest (-3.5% and -3.1%, respectively) and after exercise (-6.3% and 
      4.7%, respectively), a thicker near wall (+4.8% and +4.2%, respectively), far
      wall (both +6.2%), and mean intima-media thickness (+5.7% and +5.3%,
      respectively) and more plaques (+54.2% and +54.3%, respectively). In addition,
      they also showed increased stiffness parameters (e.g. pulse wave velocity both
      +3.6%). Less clear differences in CV risk profile and subclinical atherosclerosis
      parameters were observed when participants were stratified by LDL-c level.
      Furthermore, apoB but not LDL-c detected prevalent CVD, and non-HDL-c only
      detected prevalent CVD in men. The discriminatory power for prevalent CVD
      expressed as area under the receiver operating characteristic curve was 0.60 (P <
      0.001) for apoB, 0.57 (P = 0.001) for non-HDL-c and 0.54 (P = 0.108) for LDL-c.
      CONCLUSION: Our data support the use of first apoB and secondly non-HDL-c above
      LDL-c for identifying individuals from the general population with a compromised
      CV phenotype.

PMID- 21091809
TI  - Obesity, smoking and secular trends in cardiovascular risk factors in middle-aged
      women: data from population studies in Goteborg from 1980 to 2003.
AB  - BACKGROUND: To study the trends in cardiovascular risk factors in middle-aged
      city-dwelling Swedish women from 1980 to 2003. METHODS: Using cross-sectional
      population-based surveys, five random population samples of a total of 1915 women
      aged between 45 and 54 years, participating in the BEDA study in 1980, WHO MONICA
      studies in 1985, 1990 and 1995, and a study of 50-year-old women in 2003 were
      measured for the following parameters: anthropometry, serum cholesterol and
      triglyceride levels, smoking habits, blood pressure, physical activity and
      stress. RESULTS: Over almost 25 years, middle-aged women gained on average 4.4 kg
      in weight, with a net increase in body mass index (BMI) from 24.7 to 25.6 kg m-2.
      The proportion of participants classified as obese (>=30 kg m-2) increased by 50%
      from 10.4% to 15.1%. Women who were smokers in 2003 did not have lower BMI values
      than nonsmokers. Mean serum cholesterol concentrations decreased markedly,
      whereas smoking habits did not significantly change. The prevalence of
      hypertension decreased by 8%, whereas that of diabetes remained stable at around
      2%. Optimal risk factor status - no smoking, normotension and serum cholesterol
      <5 mmol l-1 - was present in less than one in six women in 2003, and similar
      across BMI categories. CONCLUSION: The favourable decline in cholesterol levels
      and hypertension and the increase in leisure time physical activity were offset
      by an increase in obesity, triglyceride levels and experience of stress, with
      only a minority of participants (less than one in six) having an optimal level of
      risk factors with respect to smoking, serum cholesterol and hypertension in 2003.
      This applied also to overweight and obese women. In earlier cohorts, subjects
      with low BMI values were more often smokers, whereas the opposite is observed in
      recent cohorts. Thus, women who smoke no longer have the advantage of lower
      weight.

PMID- 21091810
TI  - Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men.
AB  - OBJECTIVES: the results of experimental studies suggest that vitamin D deficiency
      activates the renin-angiotensin system and predisposes to hypertension. Results
      of previous epidemiological studies investigating the association between 25
      hydroxyvitamin D [25(OH)D] status and hypertension have not been consistent,
      perhaps because of their sole reliance on office blood pressure (BP) measurements
      leading to some misclassification of hypertension status. No previous studies
      have examined the association between 25(OH)D status and confirmed hypertension
      assessed with both office and 24-h BP measurements. DESIGN: in this cross
      sectional study, we investigated 833 Caucasian men, aged 71 +/- 0.6 years, to
      determine the association between plasma 25(OH)D concentrations, measured with
      high-pressure liquid chromatography mass spectrometry, and the prevalence of
      hypertension. We used both supine office and 24-h BP measurements for classifying
      participants as normotensive or confirmed hypertensive; participants with
      inconsistent classifications were excluded. RESULTS: in a multivariable adjusted
      logistic regression model, men with 25(OH)D concentrations <37.5 nmol L(-1) had a
      3-fold higher prevalence of confirmed hypertension compared to those with >= 37.5
      nmol L(-1) 25(OH)D (odds ratio = 3.3, 95% CI: 1.0-11.0). CONCLUSIONS: our results
      show that low plasma 25(OH)D concentration is associated with a higher prevalence
      of confirmed hypertension.

PMID- 21091811
TI  - Candidate chemosensory ionotropic receptors in a Lepidoptera.
AB  - A new family of candidate chemosensory ionotropic receptors (IRs) related to
      ionotropic glutamate receptors (iGluRs) was recently discovered in Drosophila
      melanogaster. Through Blast analyses of an expressed sequenced tag library
      prepared from male antennae of the noctuid moth Spodoptera littoralis, we
      identified 12 unigenes encoding proteins related to D. melanogaster and Bombyx
      mori IRs. Their full length sequences were obtained and the analyses of their
      expression patterns suggest that they were exclusively expressed or clearly
      enriched in chemosensory organs. The deduced protein sequences were more similar
      to B. mori and D. melanogaster IRs than to iGluRs and showed considerable
      variations in the predicted ligand-binding domains; none have the three glutamate
      interacting residues found in iGluRs, suggesting different binding specificities.
      Our data suggest that we identified members of the insect IR chemosensory
      receptor family in S. littoralis and we report here the first demonstration of IR
      expression in Lepidoptera.

PMID- 21091812
TI  - Paleogenomic data suggest mammal-like genome size in the ancestral amniote and
      derived large genome size in amphibians.
AB  - An unsolved question in evolutionary genomics is whether amniote genomes have
      been expanding or contracting since the common ancestor of this diverse group.
      Here, we report on the polarity of amniote genome size evolution using genome
      size estimates for 14 extinct tetrapod genera from the Paleozoic and early
      Mesozoic Eras using osteocyte lacunae size as a correlate. We find substantial
      support for a phylogenetically controlled regression model relating genome size
      to osteocyte lacunae size (P of slopes <0.01, r2=0.65, phylogenetic signal
      lambda=0.83). Genome size appears to have been homogeneous across Paleozoic crown
      tetrapod lineages (average haploid genome size 2.9-3.7 pg) with values similar to
      those of extant mammals. The differentiation in genome size and underlying
      architecture among extant tetrapod lineages likely evolved in the Mesozoic and
      Cenozoic Eras, with expansion in amphibians, contractions along the diapsid
      lineage, and no directional change within the synapsid lineage leading to
      mammals.

PMID- 21091813
TI  - The effect of mating system on growth of Arabidopsis lyrata in response to
      inoculation with the biotrophic parasite Albugo candida.
AB  - The effects of variation in host reproductive systems on response to pathogens
      are not well understood. We inoculated individuals from outcrossing and
      inbreeding populations of North American Arabidopsis lyrata with Albugo candida
      (white blister rust) to test the effect of mating system and heterozygosity on
      disease response. We observed three host infection phenotypes, classified as
      fully resistant, partially resistant and fully susceptible. Overall, inbreeding
      populations had more susceptible and fewer partially resistant individuals than
      outcrossing populations, but the highest proportion of resistant individuals was
      found in two of the inbreeding populations. Mating system did not affect relative
      growth rate of inoculated plants, but there were strong effects of population and
      infection phenotype. We conclude that mating system per se does not determine the
      resistance of natural A. lyrata populations to infection by Albugo, but that the
      increased variability in responses among inbreeding populations may be due to
      reduced effective population size.

PMID- 21091814
TI  - Diagnostic performance of myocardial innervation imaging using MIBG scintigraphy
      in differential diagnosis between dementia with lewy bodies and other dementias:
      a systematic review and a meta-analysis.
AB  - BACKGROUND AND PURPOSE: This study was designed to review the diagnostic
      performance of myocardial innervation imaging using iodine-123
      metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between
      dementia with Lewy bodies (DLB) and other dementias. METHODS: A comprehensive
      computer literature search of studies published through May 2010 regarding MIBG
      scintigraphy in patients with DLB was performed in PubMed/MEDLINE and Embase
      databases. Only studies in which MIBG scintigraphy was performed for differential
      diagnosis between DLB and other dementias were selected. Pooled sensitivity and
      specificity of MIBG scintigraphy were presented with a 95% confidence interval
      (CI). The area under the ROC curve was calculated to measure the accuracy of MIBG
      scintigraphy in differential diagnosis between Lewy body diseases and other
      dementias. RESULTS: Ultimately, we identified 8 studies comprising a total of 346
      patients with dementia (152 patients with DLB and 194 patients with other
      dementias). The pooled sensitivity of MIBG scintigraphy in detection of DLB was
      98% (95% CI, 94-100%); the pooled specificity of MIBG scintigraphy in
      differential diagnosis between DLB and other dementias was 94% (95% CI, 90-97%).
      The area under the ROC curve was .99. CONCLUSIONS: Myocardial innervation imaging
      with MIBG scintigraphy demonstrated high pooled sensitivity and specificity in
      patients with suspected DLB. MIBG scintigraphy is an accurate test for
      differential diagnosis between DLB and other dementias.

PMID- 21091815
TI  - A diffusion tensor imaging study in essential tremor.
AB  - BACKGROUND AND PURPOSE: Essential tremor (ET) is suggested to be a neural
      degenerative disease. The authors investigated the fractional anisotropy (FA) and
      apparent diffusion coefficient (ADC) value in basal ganglia, thalamus, red
      nucleus, and substantia nigra in ET patients using diffusion tensor image (DTI).
      METHODS: DTI examination was carried out in patients with ET and controls. FA and
      ADC values were obtained from various brain structures, including caudate,
      putamen+pallidum, thalamus, red nucleus, and substantia nigra. RESULTS: The ADC
      value of the red nuclei in patients with ET was higher compared with controls
      (.90 vs .77; P= .000). However, no significant differences were demonstrated for
      FA, or ADC values of other structures. CONCLUSIONS: The increased ADC value in
      the red nucleus indicates that there is neuronal damage or loss present,
      suggesting that ET may be a neurodegenerative disease.

PMID- 21091816
TI  - A comparison of gray matter density in restless legs syndrome patients and
      matched controls using voxel-based morphometry.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common neurological disorder the
      pathophysiology of which is incompletely understood. Four studies have examined
      structural differences between the brains of RLS patients and healthy controls,
      using voxel-based morphometry (VBM). All 4 studies have provided different
      results. METHODS: Optimized VBM was used to search for structural differences in
      gray matter density. Sixteen RLS patients naive to dopaminergic drugs and 16 age-
      and sex-matched controls received structural T1-weighted MR scans. Structural
      data were analyzed using FSL-VBM. RESULTS: No difference in gray matter density
      was detected between the two groups (voxel-wise significance: no significant
      voxels at P= .89 (whole brain Family Wise Error (FWE) corrected); no significant
      voxels at P < .05 (whole brain False Discovery Rate (FDR) corrected; smallest
      achievable FDR threshold .99). CONCLUSION/DISCUSSION: The present study did not
      replicate (confirm) previous findings of structural brain changes in RLS, but
      instead supported the findings of a recent study showing a lack of gray matter
      alteration in an elderly RLS population. More specifically, the results do not
      support neuronal loss as an underlying disease mechanism in RLS. Potential
      limitations in the application of VBM are also discussed.

PMID- 21091817
TI  - Cerebral white matter lesions in patients with Crohn's disease.
AB  - BACKGROUND: To investigate the incidence, characteristics, and predisposing
      factors for cerebral white matter lesions in patients with Crohn's disease.
      METHODS: We retrospectively evaluated the incidence and characteristics of
      cerebral T2 white matter abnormalities in 54 patients with Crohn's disease and
      compared to 100 age-matched controls. We also investigated potential co
      morbidities known to be associated with white matter abnormalities in Crohn's
      patients with normal and abnormal Magnetic Resonance Imaging (MRI). RESULTS:
      Seventy-two percent of patients with Crohn's disease had T2 white matter
      abnormalities, as compared with 34% of the age-matched controls (P < .001).
      Lesion severity and size were not significantly different between the two groups;
      however, periventricular distribution and fulfillment of the Barkhof MRI criteria
      were overrepresented in Crohn's population. History of hypertension, diabetes,
      and migraine; gender, duration of disease and prior exposure to anti-tumor
      necrosis factor were not significantly different between Crohn's patients with
      and without white matter abnormalities; however, patients with lesions were
      significantly older than those without. CONCLUSIONS: Patients with Crohn's
      disease have a higher incidence of white matter T2 hyperintensities as compared
      with controls. Age was the only significant factor for the abnormalities within
      Crohn's group. White matter T2 hyperintensities are likely another extra
      intestinal manifestation of Crohn's disease.

PMID- 21091818
TI  - Intracranial Rosai-Dorfman disease with unusual transcranial extension.
AB  - A 48-year-old woman presented with a growing palpable mass at the left frontal
      area. The imaging studies and histopathological examination of the mass was
      consistent with dural-based Rosai-Dorfman disease with unusual transcranial
      extension. We reported this case not only because of its rarity, but also because
      of the infiltrative pattern. The infiltrative nature presented in this case may
      be taken into consideration for surgical treatment of intracranial Rosai-Dorfman
      disease.

PMID- 21091819
TI  - Typical imaging findings in posterior reversible encephalopathy syndrome (PRES).

PMID- 21091820
TI  - Update on magnetic resonance angiography of the circle of Willis in patients with
      symptomatic intracranial neuropathology.

PMID- 21091821
TI  - Brain imaging in cerebellar ataxia associated with autoimmune polyglandular
      syndrome type 2.
AB  - Autoimmune polyglandular syndrome (APS) type 2 (Schmidt syndrome) is a disorder
      characterized by a combination of autoimmune adrenal insufficiency, autoimmune
      thyroid disease, and type 1 autoimmune diabetes mellitus. We describe the first
      case of subacute cerebellar syndrome associated with APS type 2. Brain magnetic
      resonance imaging showed atrophy of the cerebellum and the vermis, as well as of
      the anterior pituitary gland. Magnetic resonance spectroscopy showed decreased N
      acetylaspartate/creatine ratio in the cerebellum and in the pons. Our findings
      expand the spectrum of neurological deficits in APS type 2 and underlines that
      cerebellar pathways may be a main target of the disorder.

PMID- 21091822
TI  - The shortage of on-call surgical specialist coverage: a national survey of
      emergency department directors.
AB  - OBJECTIVES: problems with on-call specialist physician coverage have been
      identified as a significant issue for our nation's health care system. Despite
      this, little is known about the full extent of these coverage deficiencies in
      emergency departments (EDs), their effect on emergency care provision, or the
      subsequent effect on patient flow should specialist-requiring patients need to be
      transferred to centers of higher-level care. The objective was to report the
      experiences of a national sample of ED directors regarding the degree of
      difficulty in providing specialist coverage and the effect of on-call coverage
      problems on emergency patient care. METHODS: the authors conducted a cross
      sectional self-administered survey of a national sample of ED directors. How
      frequently ED directors reported on-call coverage problems, whether they recently
      lost on-call coverage, whether their current on-call coverage was reliable, and
      the potential effect on emergency care provision were all assessed. RESULTS: the
      overall response rate was 62% (442 of 715). Seventy-four percent of respondents
      reported on-call coverage problems with specialist physicians. Sixty percent
      reported having lost 24/7 coverage for at least one specialty in the past 4
      years. Twenty-six percent reported unreliability in their current on-call
      coverage. Twenty-three percent noted that their trauma center designation level
      had been affected by on-call coverage, and 22% noted an increase in patients
      leaving before being seen by a medically needed specialist. CONCLUSIONS:
      difficulties in obtaining specialty on-call coverage are a pervasive issue for
      EDs at the national level. Emergency care provision appears to have been
      affected, and this issue is further impacted by a perceived unreliability in
      current on-call coverage provision as well as the attrition of coverage for
      individual specialties.

PMID- 21091823
TI  - Acral amelanotic verrucous melanoma: dermoscopic findings.

PMID- 21091824
TI  - Transmission of Pseudomonas aeruginosa from nail to wound infection.

PMID- 21091825
TI  - Acute fatal fat tissue embolism after autologous fat transfer in a patient with
      lupus profundus.

PMID- 21091826
TI  - Bowen's disease associated with human papillomavirus infection of the nail bed.

PMID- 21091827
TI  - Cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV
      infected individuals in Mexico.
AB  - OBJECTIVE: Maraviroc is the first approved drug in a new class of
      antiretrovirals, the CCR5 antagonists. The objective of this study was to predict
      the long-term clinical impact and cost-effectiveness of maraviroc in treatment
      experienced adults with HIV/AIDS in Mexico. METHODS: The AntiRetroviral Analysis
      by Monte Carlo Individual Simulation (ARAMIS) model was adapted to the Mexican
      context to predict clinical and economic outcomes of treating with optimized
      background therapy (OBT) versus testing for viral tropism status and treating
      with OBT +/- maraviroc accordingly in treatment-experienced adults in Mexico.
      Baseline characteristics and efficacy were from the MOTIVATE trials' screening
      cohort. Costs and population mortality data were specific to Mexico. Results were
      reported from the perspective of health care payers in 2008 Mexican pesos
      (converted to 2008 US$ in parentheses). RESULTS: Compared to treatment with OBT
      alone, treatment with OBT +/- maraviroc contingent on tropism test result
      increased projected undiscounted life expectancy and discounted quality-adjusted
      life expectancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life
      years (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). The
      resultant incremental cost-effectiveness ratio (ICER) was $453,978 (US$42,429)
      per QALY gained. The ICER was somewhat lower when maraviroc was modeled in
      individuals susceptible to <= 2 components of OBT ($407,329; US$38,069), while
      the ICER was higher in individuals susceptible to >=3 OBT components ($718,718;
      US$67,171). CONCLUSION: In treatment-experienced individuals with HIV/AIDS in
      Mexico, maraviroc may be cost-effective, particularly in individuals with limited
      options for active antiretroviral therapy (ART).

PMID- 21091828
TI  - Management of hypertrophic pylorus stenosis with ultrasound guided single shot
      epidural anaesthesia--a retrospective analysis of 20 cases.
AB  - AIM: To retrospectively describe the performance of ultrasound guided thoracic
      epidural anaesthesia under sedation for anaesthesia management of open
      pyloromyotomy. BACKGROUND: Anaesthesia management for hypertrophic pylorus
      stenosis (HPS) is usually performed under general anaesthesia with tracheal
      intubation. Only a few publications describe avoidance of tracheal intubation in
      infants by using spinal or caudal anaesthesia. The present retrospective analysis
      describes the performance of ultrasound guided thoracic epidural anaesthesia
      under sedation for anaesthetic management of open pyloromyotomy. METHODS: Twenty
      consecutive infants scheduled for pyloromyotomy according to the Weber-Ramstedt
      technique were retrospectively analysed. After sedation with nalbuphine and
      propofol, an ultrasound guided single shot thoracic epidural anaesthesia was
      performed with 0.75 ml.kg(-1) ropivacaine 0.475%. Insufficient blockade was
      defined as increase of HR > 15% from initial value and/or any movements at skin
      incision. In those cases we were prepared for rapid sequence intubation according
      to the departmental standard. RESULTS: All pyloromyotomies could be performed
      under single shot thoracic epidural anaesthesia and sedation. One case of
      moderate oxygen desaturation was treated with intermittent ventilation via face
      mask. CONCLUSIONS: Thoracic epidural anaesthesia under sedation for pyloromyotomy
      has been a useful technique in this retrospective series of infants suffering
      from HPS. In 1/20 infants short term assisted ventilation via face mask was
      required. Undisturbed surgery was possible in all cases.

PMID- 21091829
TI  - Comparison of effective inspired concentration of sevoflurane in preterm infants
      with different postconceptual ages.
AB  - OBJECTIVE: Screening examination for retinopathy of prematurity (ROP) is
      stressful and painful to the neonate. Sevoflurane has been used successfully in
      anesthesia for full-term and premature neonates and has been recently used for
      pediatric outpatient procedures. In this study, we examined the effective
      inspired concentration of sevoflurane to prevent movement in response to
      stimulation of examination in 50% of patients (EIC50) of sevoflurane, as well as
      the response of sevoflurane to age in the preterm outpatients undergoing fundus
      examination. METHODS: Preterm pediatric outpatients at different postconceptual
      ages (duration from the mother's last menstrual period to the date when the
      examination for ROP was performed) with <44 weeks (group A) and 44-64 weeks
      (group B) undergoing fundus examination were included. SpO(2) and ECG were
      monitored in operation room. In the process of anesthetic induction, the oxygen
      flow rates were 3 l.min(-1), and subjects spontaneously breathed 6% sevoflurane
      by mask. The time to loss of movement was recorded as induction time. Six percent
      sevoflurane was inhaled continuously for the same duration, and then the inspired
      concentration of sevoflurane was adjusted to maintenance concentration. When no
      movement or crying was observed, the speculums were used to keep the eyelids
      open, and then the eye examinations were performed by the same ophthalmologist.
      During induction time and maintenance time, the occurrence of coughing,
      clenching, gross purposeful movement, breath holding or desaturation to SpO(2) <
      95% was recorded. After completion of the procedure, patients were observed in
      the same room until spontaneous eye opening or verbalization occurred. Up and
      down method was used to determine subsequent maintenance concentration in each
      group. The initial maintenance concentration was 3%. The gradient of increase or
      decrease was 0.5%. If the preceding subject had not moved, the sevoflurane
      concentration was decreased by 0.5%; if the preceding subject had moved, the
      concentration was increased by 0.5%. When at least six independent alternations
      from no-movement to movement were observed, test was terminated. RESULTS: Twenty
      four pediatric outpatients completed the investigation in group A. The effective
      inspired concentration prevented movement in response to stimulation of
      examination in 50% of patients (EIC50) of sevoflurane was 2.5% in group A. Twenty
      seven patients completed the investigation and EIC50 values of sevoflurane were
      3.0% in group B. The induction time in group A was significantly lower than that
      in group B. The gestational ages, anesthesia time, and awake time were similar in
      two groups. CONCLUSION: Anesthesia with inhaled sevoflurane by a face mask can be
      accomplished in preterm outpatients undergoing fundus examination without
      intubation and i.v. accession. The EIC50 is lower, and the induction time is
      shorter in smaller aged patients compared with those in older ones.

PMID- 21091830
TI  - Evolution of Pseudomonas aeruginosa virulence in infected patients revealed in a
      Dictyostelium discoideum host model.
AB  - Pseudomonas aeruginosa can cause acute lung infections in intubated patients or
      chronic infections in patients with cystic fibrosis (CF). In both situations, P.
      aeruginosa accumulates specific mutations, in particular in the lasR quorum
      sensing regulator gene. Using a Dictyostelium discoideum amoeba model, we
      assessed whether these mutations affect bacterial virulence. Among a collection
      of clinical isolates from 16 CF patients, initial isolates were fully virulent in
      15 patients, but for late isolates collected several years later, virulence was
      decreased in eight patients. No significant correlation between genetic
      inactivation of lasR and decreased virulence was observed. Among strains isolated
      from ten colonized intubated patients, all initial isolates were fully virulent.
      Despite the accumulation of lasR-inactivating mutations in strains collected over
      a 3-week period, no decrease in virulence was observed in eight of 10 patients.
      In one intubated patient, the virulent initial strain was replaced a few days
      later with a different, less virulent, strain. We observed a gradual decrease in
      bacterial virulence in only one intubated patient. We conclude that adaptation of
      P. aeruginosa to chronically infected CF patients can lead to a slow and gradual
      loss of virulence, as measured in a Dictyostelium model system. However, loss of
      virulence is not caused predominantly by mutations in lasR. During short-term
      colonization of intubated patients for up to 20 days, a decrease in virulence was
      exceptional, despite the accumulation of lasR mutations.

PMID- 21091831
TI  - Evolving epidemiology of hepatitis C virus.
AB  - More than 20 years after the discovery of the hepatitis C virus (HCV), it is now
      well established that HCV is of global importance affecting all countries,
      leading to a major global health problem that requires widespread active
      interventions for its prevention and control. Chronic hepatitis C was linked to
      the development of cirrhosis and hepatocellular carcinoma in many areas of the
      world. Current epidemiological assessments have identified complex patterns with
      highly variable local prevalence rates between countries and within countries.
      HCV infection patterns have not significantly changed in most parts of the world
      since 1997, when first analyzed, partly due to the lack of new and more accurate
      data. The assessment of the national HCV prevalence and transmission modes should
      be completed to enable national authorities to prioritize preventive measures and
      to make the most appropriate use of available resources. The 'patchy'
      epidemiological situation in some areas will continue to complicate the task of
      the establishment of global, regional and national base line data. The present
      assessment finds a global prevalence of 2.35%, affecting 160 million chronically
      infected individuals. There is an urgent need for more accurate Information on
      the costs and burden of HCV to society. Twenty-one year after the discovery of
      HCV, the assessment is far from being complete and little progress has been made
      in the past 10 years in many countries. In some countries significant increases
      have been reported and this may also apply to countries were insufficient data
      exist. A safe and efficient vaccine against HCV is urgently needed.

PMID- 21091832
TI  - Preliminary validation of a novel high-resolution melt-based typing method based
      on the multilocus sequence typing scheme of Streptococcus pyogenes.
AB  - The major limitation of current typing methods for Streptococcus pyogenes, such
      as emm sequence typing and T typing, is that these are based on regions subject
      to considerable selective pressure. Multilocus sequence typing (MLST) is a better
      indicator of the genetic backbone of a strain but is not widely used due to high
      costs. The objective of this study was to develop a robust and cost-effective
      alternative to S. pyogenes MLST. A 10-member single nucleotide polymorphism (SNP)
      set that provides a Simpson's Index of Diversity (D) of 0.99 with respect to the
      S. pyogenes MLST database was derived. A typing format involving high-resolution
      melting (HRM) analysis of small fragments nucleated by each of the resolution
      optimized SNPs was developed. The fragments were 59-119 bp in size and, based on
      differences in G+C content, were predicted to generate three to six resolvable
      HRM curves. The combination of curves across each of the 10 fragments can be used
      to generate a melt type (MelT) for each sequence type (ST). The 525 STs currently
      in the S. pyogenes MLST database are predicted to resolve into 298 distinct MelTs
      and the method is calculated to provide a D of 0.996 against the MLST database.
      The MelTs are concordant with the S. pyogenes population structure. To validate
      the method we examined clinical isolates of S. pyogenes of 70 STs. Curves were
      generated as predicted by G+C content discriminating the 70 STs into 65 distinct
      MelTs.

PMID- 21091833
TI  - High incidence of peripheral blood plasmacytosis in patients with dengue virus
      infection.
AB  - Little is known about polyclonal peripheral blood plasmacytosis in dengue virus
      (DENV)-infected patients. We initiated this prospective observational study to
      quantify and describe the kinetics and phenotype of peripheral blood plasma cells
      (PCs) in these patients. Morphological examination and flow cytometric (FC)
      analysis for the characterization and immunophenotyping of lymphocyte subsets and
      PCs were performed in 35 and 31 patients suspected of DENV infection,
      respectively. Our results show that blood plasmacytosis is a very common
      haematological finding. Depending on the days of illness at presentation, blood
      plasmacytosis was observed in 64% to 73% of patients. Blood plasmacytosis was
      most pronounced before 7 days of illness and declined rapidly thereafter, to
      completely disappear after 14 days of illness. Blood plasmacytosis was higher in
      secondary DENV infection. The majority of CD138(+) PCs (89%) had a shared
      immunophenotype (CD45(+)/CD19(-)/CD56(-)) and in all cases the PCs were
      polyclonal. Blood plasmacytosis, characterized by a transient presence of
      polyclonal PCs in the circulation, is a common event in DENV infection.

PMID- 21091834
TI  - Histological progression of small intrapulmonary metastatic tumor from primary
      lung adenocarcinoma.
AB  - The histopathology of small metastases is thought to reflect the early metastatic
      process. To clarify the morphological features of early metastatic tumor
      progression, we analyzed the histological heterogeneity of many small
      intrapulmonary metastases. Histological typing based on the World Health
      Organization classification (bronchioloalveolar carcinoma, acinar, papillary, and
      solid subtype) was used to evaluate 234 metastases from the primary lung
      adenocarcinomas of 139 patients. The predominant subtype of metastasis 3 mm or
      less in diameter was bronchioloalveolar carcinoma when the primary lesion was
      diagnosed as predominant bronchioloalveolar carcinoma, acinar, and papillary
      subtype. When the histology of the primary tumor was predominantly a solid
      subtype, the predominant subtype of metastatic tumor was also a solid subtype.
      However, analysis of metastases that were more than 3 mm showed that the
      predominant subtype of the metastasis reflected the predominant subtype of the
      primary tumor. Furthermore, we evaluated the number of subtypes in primary and
      metastatic tumors. As the metastasis grew larger, the number of subtypes in the
      metastatic lesion increased and came close to the number composed in the primary
      lesion. These findings suggest that implanted cancer cells display lepidic growth
      in the early metastatic phase and recapitulate the morphological heterogeneity of
      the original tumor as the metastasis enlarges.

PMID- 21091835
TI  - Frequent expression of gp46 in adult T-cell leukemia/lymphoma: an
      immunohistochemical study of 40 cases.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disease caused by
      human T-cell lymphotropic virus type 1 (HTLV-1) infection. HTLV-1 is spread by
      cell-to-cell transmission via the gp46-197 region, from Asp197 to Leu216, in the
      envelope protein gp46. A correlation exists between the prevalence and titer of
      the antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the
      severity of ATLL. In the present study, immunohistochemical staining was
      performed on samples of paraffin embedded lymph nodes of three different
      histological types of ATLL (anaplastic large cell type, n = 10; pleomorphic type,
      n = 10; and Hodgkin's-like type, n = 10) from 30 cases and 10 cases of HTLV
      associated lymphadenitis. Of the three ATLL subtypes, gp46 expression was highest
      in the anaplastic large cell type, followed by the pleomorphic type and Hodgkin's
      like type (mean: 53.4%, 34.9% and 16.0%, respectively; P= 0.0003). In HTLV-1
      associated lymphadenitis cases, gp46 positive cells were rarely seen (4.0%).
      These results suggest that gp46-197 immunohistochemical staining can be a useful
      histological indicator for prediction of the aggressiveness of ATLL and prognosis
      for ATLL patients.

PMID- 21091836
TI  - Idiopathic segmental ureteritis, misdiagnosed as ureteral cancer preoperatively:
      a case report with literature review.
AB  - A 53-year-old man presented with right flank pain for 6 days. Computerized
      tomography revealed a 3 cm long segment of ureteral narrowing with wall
      thickening and hydronephrosis, suspicious for ureteral cancer. Under the clinical
      diagnosis of ureteral carcinoma a right nephroureterectomy was performed. The
      wall of the distal ureter, 2.5 cm from the bladder cuff, had a luminal-narrowing,
      firm mass-forming lesion with abrupt transition from the adjacent ureter.
      Histologically, the resected ureteral mass showed transmural fibrosing, chronic
      inflammation with numerous plasma cells, epithelioid granulomas, and obliterative
      phlebitis. Histological findings were consistent with idiopathic segmental
      ureteritis (ISU) with differential diagnoses of IgG4-related sclerosing disease,
      including lymphoplasmacytic inflammatory pseudotumor (IPT) and idiopathic
      retroperitoneal fibrosis. IgG4 immunostaining in this case was barely positive,
      excluding the possibility of IgG4-related IPT. Although the majority of luminal
      obliterated segmental lesions of the ureter are neoplastic in nature, non
      neoplastic inflammatory processes as seen in this case may occur in the ureter,
      causing diagnostic confusion with true neoplasms. Herein we report a rare case of
      ISU that was clinically misdiagnosed as malignancy preoperatively. ISU of the
      current case may be an IgG4-unrelated subtype of IPT.

PMID- 21091837
TI  - Dermatofibrosarcoma protuberans of the breast skin.
AB  - A case of a 26-year-old woman with dermatofibrosarcoma protuberans of the breast
      skin is described. She had noticed a palpable mass with redness 15 years
      previously, but it had begun to grow rapidly with swelling and redness two months
      before presenting. Ultrasonography and biopsy demonstrated a possibility of
      sarcoma of the breast. Wide excision was performed to confirm the diagnosis.
      Histologically, the tumor was composed of a uniform population of fibroblasts in
      a distinct storiform pattern. CD34 immunostaining showed diffuse reactivity.
      Platelet-derived growth factor beta break-apart fluorescence in situ
      hybridization analysis showed a split-signal pattern which supported the
      diagnosis of dermatofibrosarcoma protuberans in the skin of the breast. It is
      important to diagnose a soft tissue lesion accurately when it occurs in the
      breast.

PMID- 21091838
TI  - Atypical soft tissue perineurioma in the tongue of a young girl.
AB  - Perineuriomas are uncommon benign peripheral nerve sheath tumors that include
      soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue
      perineuriomas arise in a wide anatomic distribution and mostly in patients older
      than 20 years of age. We report an atypical perineurioma in a 7-year-old girl.
      The tumor, located in the tongue, was uniformly hypercellular. The tumor cells
      were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process
      formation and wavy elongated nuclei, and the architecture was composed of
      predominantly short fascicles with areas exhibiting a vague storiform pattern.
      Although the tumor cells generally appeared bland, the tumor showed worrisome
      features including an infiltrative pattern and occasional mitotic figures.
      Psammoma bodies were observed in the periphery of the tumor.
      Immunohistochemically, the cells were positive for epithelial membrane antigen,
      vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type
      IV collagen. The authors document a case of soft tissue perineurioma with
      atypical histological features that occurred in the tongue of a child.

PMID- 21091839
TI  - A case of hepatocellular carcinoma developed after allogeneic bone marrow
      transplantation.

PMID- 21091842
TI  - Electronic working length determination in primary teeth by ProPex and Digital
      Signal Processing.
AB  - The purpose of this study was to evaluate the accuracy of electronic apex
      locators Digital Signal Processing (DSP) and ProPex, for root canal length
      determination in primary teeth. Fifteen primary molars (a total of 34 root
      canals) were divided into two groups: Group I - without physiological resorption
      (n = 16); and Group II - with physiological resorption (n = 18). The length of
      each canal was measured by introducing a file until its tip was visible and then
      it was retracted 1 mm. For electronic measurement, the devices were set to 1 mm
      short of the apical resorption. The data were analysed statistically using the
      intraclass correlation coefficient (ICC). Results showed that the ICC was high
      for both electronic apex locators in all situations - with (ICC: DSP = 0.82 and
      Propex = 0.89) or without resorption (ICC: DSP = 0.92 and Propex = 0.90). Both
      apex locators were extremely accurate in determining the working length in
      primary teeth, both with or without physiological resorption.

PMID- 21091843
TI  - Correlation between sealer penetration and microleakage following the use of MTAD
      as a final irrigant.
AB  - The relationship between sealer penetration and apical microleakage following the
      use of MTAD as an irrigant in root canal procedures was evaluated. A collection
      of 120 human teeth was divided into three groups of 40 in each group. The final
      rinse was varied as follows: group 1 - the final rinse was saline solution, group
      2 - ethylene diamine tetraacetic acid and for group 3 - MTAD. Each group was then
      divided into two subgroups (20 teeth) and filled with gutta percha and either AH
      Plus or Dorifill sealer. Half of the teeth were selected for dye penetration
      testing and the sealer penetration in the remaining teeth was evaluated using
      scanning electron microscope. There were no significant differences between the
      three irrigants, but there was less dye penetration in teeth sealed with AH Plus
      than Dorifill. Penetration of the sealer was better in the MTAD and ethylene
      diamine tetraacetic acid groups than in the saline group. Statistically, there
      was no significant difference between the sealer penetration into the dentinal
      tubules and the dye penetration.

PMID- 21091844
TI  - Microsurgical endodontic retreatment of post restored posterior teeth: a case
      series.
AB  - Post-treatment apical periodontitis may persist due to biological factors as
      outlined by Nair or when treatment procedures have been ineffective in
      eliminating the intraradicular infection. This case series reports on the
      management of five posterior teeth restored with posts where microsurgical
      techniques were employed utilising the operating microscope, ultrasonics, micro
      instrumentation and mineral trioxide aggregate as a root-end filling material.
      Healing was evident at 12-month review appointments. Microsurgical techniques
      have significantly improved the outcomes for healing of periapical lesions when
      compared to traditional approaches to endodontic surgery. Success rates have been
      shown to be comparable with conventional orthograde treatment.

PMID- 21091845
TI  - Teeth with double internal inflammatory resorption: report of two cases.
AB  - Internal inflammatory resorption is an uncommon condition, which requires the
      presence of necrotic and infected pulp tissue within the coronal portion of the
      root canal system as well as inflamed pulp tissue apical to the resorptive
      defect. The defect usually appears as a bowl-shaped radiolucency within the tooth
      root. Most cases are asymptomatic and many cases are only seen once the entire
      pulp has necrosed and all of the root canal system is infected resulting in
      apical periodontitis. The two cases presented are unusual in that they both had
      two distinct areas of internal inflammatory resorption. It is hypothesised that
      the more coronal lesion occurred first and then it ceased to continue resorbing
      the root in that position as the 'necrotic, infected front' moved apically at
      which time a second resorptive defect developed. The management, using different
      approaches, of these two cases of 'double internal inflammatory resorption' is
      described.

PMID- 21091846
TI  - Combined androgen blockade for prostate cancer: review of efficacy, safety and
      cost-effectiveness.
AB  - A standard treatment for advanced prostate cancer is androgen deprivation by
      surgical or medical castration. In theory, however, combined androgen blockade
      (CAB) with an antiandrogen plus castration should be more effective because
      castration alone does not completely eliminate androgens in the prostate.
      Therefore, a number of randomized clinical trials (RCT) were conducted in the
      1990s to investigate the efficacy of CAB with an antiandrogen (nilutamide or
      flutamide) plus castration; however, there were both positive and negative
      results for the efficacy of CAB. The lack of data on safety, quality of life
      (QOL) and cost-effectiveness has been a hindrance to the adoption of CAB for the
      treatment of prostate cancer. Nevertheless, discussion on CAB for the treatment
      of prostate cancer has continued for over 20 years, which suggests that there
      remains some hope for this regimen. In the 2000s, clinical research on CAB with
      the antiandrogen bicalutamide commenced. CAB using this new antiandrogen was
      found to prolong overall survival (OS) in patients with prostate cancer, with
      favorable safety profiles and cost-effectiveness, without deteriorating QOL. In
      this article, we discuss the feasibility of CAB with bicalutamide for the
      treatment of prostate cancer by reviewing the theoretical background of CAB and
      then the results of RCT conducted in the 1990s when the usefulness of CAB was
      assessed.

PMID- 21091847
TI  - Hedgehog signaling pathway mediates the progression of non-invasive breast cancer
      to invasive breast cancer.
AB  - The purpose of this study is to clarify the contribution of the Hedgehog
      signaling pathway (Hh pathway) to the progression from ductal carcinoma in situ
      (DCIS) to invasive ductal carcinoma (IDC). A total of 149 surgically resected
      mammary disease specimens and 12 sentinel lymph nodes with micro-metastasis (Ly
      met) were studied. The degree of Hh pathway activation was estimated from the
      Gli1 nuclear staining ratio (%Gli1 nuclear translocation) in cancer cells. The
      invasiveness of breast cancer cells was determined using Matrigel assays. A
      serial increase of %Gli1 nuclear translocation to IDC from non-neoplastic
      diseases was confirmed. In tumor specimens, %Gli1 nuclear translocation
      correlated with the invasiveness of each type of mammary disease and also
      correlated with invasion-related histopathological parameters. The %Gli1 nuclear
      translocation in lymph nodes with micro-metastasis was similar to that in primary
      sites and higher than that in DCIS with microinvasion and DCIS. Blockade of the
      Hh pathway decreased the invasiveness of breast cancer cells. In IDC, %Gli1
      nuclear translocation correlated with the expression of estrogen receptor-alpha.
      Estrogen increased %Gli1 nuclear translocation and the invasiveness of estrogen
      receptor-alpha-positive cells. The Hh pathway mediates progression from a non
      invasive phenotype to an invasive phenotype and %Gli1 nuclear translocation may
      be useful as a predictive marker for evaluating the ability of invasiveness.

PMID- 21091848
TI  - Differential antiproliferation effect of 2'-benzoyloxycinnamaldehyde in K-ras
      transformed cells via downregulation of thiol antioxidants.
AB  - 2'-Benzoyloxycinnamaldehyde (BCA), one of the derivatives of 2'
      hydroxycinnamaldehyde (HCA) isolated from the bark of Cinnamomum cassia, induces
      apoptosis in human cancer cells. We found that BCA induces stronger
      antiproliferative effects in K-ras-transformed cells (RK3E-ras) than in isogenic
      non-transformed cells (RK3E). Treatment of RK3E-ras with BCA resulted in
      increased ROS generation and depletion of intracellular glutathione, whereas BCA
      treated RK3E showed no significant increase in the ROS level with concurrent
      increase in intracellular glutathione (GSH). Thiol antioxidants recovered cell
      proliferation inhibition caused by BCA in both cell lines, while non-thiol
      antioxidants failed to recover cell death. BCA decreased metallothionein (MT)
      expression in RK3E-ras, while inducing remarkable MT expression in RK3E. The
      increase of intracellular GSH in RK3E is partially caused by differential
      induction of gamma-glutamylcysteine synthetase (gamma-GCS) due to BCA treatment.
      To evaluate the upstream pathway for differential expression of gamma-GCS and MT,
      we analyzed early DJ-1 (PARK7) and NF-E2 p45-related factor 2 (Nrf2) changes
      after BCA treatment. In RK3E, DJ-1 expression considerably increased for 3 h with
      concurrent induction of Nrf2, whereas in RK3E-ras cells BCA decreased these
      protein levels. Based on these findings, it seems that the therapeutic
      selectivity of BCA in RK3E-ras results from decreased thiol antioxidants via
      decreased DJ-1 and Nrf2 expression.

PMID- 21091849
TI  - Manometric features of eosinophilic esophagitis in esophageal pressure
      topography.
AB  - BACKGROUND: Although most of the patients with eosinophilic esophagitis (EoE)
      have mucosal and structural changes that could potentially explain their
      symptoms, it is unclear whether EoE is associated with abnormal esophageal motor
      function. The aims of this study were to evaluate the esophageal pressure
      topography (EPT) findings in EoE and to compare them with controls and patients
      with gastro-esophageal disease (GERD). METHODS: Esophageal pressure topography
      studies in 48 EoE patients, 48 GERD patients, and 50 controls were compared. The
      esophageal contractile pattern was described for ten 5-mL swallows for each
      subject and each swallow was secondarily characterized based on the bolus
      pressurization pattern: absent, pan-esophageal pressurization, or
      compartmentalized distal pressurization. KEY RESULTS: Thirty-seven percent of EoE
      patients were classified as having abnormal esophageal motility. The most
      frequent diagnoses were of weak peristalsis and frequent failed peristalsis.
      Although motility disorders were more frequent in EoE patients than in controls,
      the prevalence and type were similar to those observed in GERD patients (P=0.61,
      chi-square test). Pan-esophageal pressurization was present in 17% of EoE and 2%
      of GERD patients while compartmentalized pressurization was present in 19% of EoE
      and 10% of GERD patients. These patterns were not seen in control subjects.
      CONCLUSIONS & INFERENCES: The prevalence of abnormal esophageal motility in EoE
      was approximately 37% and was similar in frequency and type to motor patterns
      observed in GERD. Eosinophilic esophagitis patients were more likely to have
      abnormal bolus pressurization patterns during swallowing and we hypothesize that
      this may be a manifestation of reduced esophageal compliance.

PMID- 21091850
TI  - Immunoglobulin isotypes and functional anti-FVIII antibodies in response to FVIII
      treatment in Balb/c and C57BL/6 haemophilia A mice.
AB  - Previous studies have demonstrated that genetic factors play an important role in
      determining the likelihood of formation of anti-factor VIII (FVIII) antibodies in
      haemophilia A patients. We were interested in characterizing the spectrum of
      FVIII antibody formation and the primary and secondary immune responses after
      FVIII administration in two different exon 16-disrupted haemophilia A mouse
      strains, Balb/c and C57BL/6. Balb/c and C57BL/6 E16 haemophilia A mice were used
      in all experiments. Total FVIII antibodies and FVIII inhibitors were measured
      using ELISA and Bethesda assays respectively. T- and B-cell cytokines were
      quantified using ELISA and flow cytometry. FVIII antibodies, but not functional
      inhibitors were detectable 1 week after the first FVIII treatment in both
      strains. These antibodies mainly belonged to the IgM and IgA isotypes. After the
      fourth FVIII treatment, neutralizing anti-FVIII antibodies were detected in both
      mouse strains: Balb/c (mean inhibitory titer 58 BU) and C57BL/6 (mean inhibitory
      titer 82 BU). IgG1 levels were similar in both strains but the IgG2A and IgG2B
      subclasses were higher in C57BL/6 mice. The results of intracellular cytokine
      staining of T cells indicated that the FVIII-treated C57BL/6 mice produced more
      IL10 and Th1 cytokines than the FVIII-treated Balb/c mice. These studies show
      that C57BL/6 mice develop a stronger immune response towards FVIII than Balb/c
      mice. We propose that the enhanced Th1 and IL10 cytokine micro-environment
      induced in C57BL/6 mice is responsible for this difference. Therefore, genetic
      strain-dependent differences must be considered when evaluating immunological
      outcomes in mouse models of haemophilia A.

PMID- 21091851
TI  - The perspective of patients with haemophilia with inhibitors and their care
      givers: preferences for treatment characteristics.
AB  - Treatment preferences of haemophilia patients with inhibitors have not been well
      documented. This study sought to identify treatment attributes that
      patients/caregivers consider most important in the USA, inasmuch as those
      preferences may affect patient adherence to treatment plans. A discrete choice
      experiment was conducted to elicit treatment preferences. Haemophilia patients
      with inhibitors, or their caregivers on their behalf, completed a written survey
      that elicited preferences for treatment features and levels synthesized from the
      medical literature including: risk of viral transmission, rise in inhibitor
      titre, reduction in thromboembolic events, number of infusions, preparation time,
      infusion time/volume, time required to stop bleeding/alleviate pain, use of
      prophylaxis, use of major surgery and medication cost. Relative importance (RI)
      of preferences was modelled using a multinomial logit function. Most respondents
      were male (49 of 51, 96.1%); mean age, 20.7 years (SD = 18.8) and 88.5% of
      patients had haemophilia type A. The three most important patient-identified
      treatment attributes were as follows: time required to stop bleeding (RI = 19.3),
      possibility that the level of inhibitor may rise (RI = 14.3) and risk of
      contracting a virus from the product (RI = 13.5). Haemophilia patients with
      inhibitors and their caregivers appear to be willing to accept treatments that
      may be more inconvenient and painful as long as the treatments are effective in
      quickly controlling bleeds, do not increase inhibitor levels and do not pose a
      risk for viral contraction. Study findings provide meaningful input to the
      clinical community from patients and caregivers and support the importance of
      physicians understanding their patients' treatment preferences.

PMID- 21091852
TI  - Prospects for person-centred diagnosis in general medicine.
AB  - Fundamental changes in health care delivery are revealing the limitations of our
      collective focus on disease-specific and technology-driven health care. We
      increasingly treat diseases, not persons, and it moves individuals from active
      participants in the care process to passive recipients of interventions. This
      problem is especially important for general medicine, where we must maintain the
      balance between person and disease, caring and technology. In this chapter, we
      focus on prospects for person-centred diagnosis and treatment in general (primary
      care) medicine in this time of change. We describe one way to employ the
      biopsychosocial model to integrate person-centred diagnosis in routine clinical
      practice, and we propose a 'person-centred path' for primary care development
      with the health information technology tools we will need to develop to follow
      that path.

PMID- 21091853
TI  - A systematic approach for uptake of evidence on sex-specific issues in guidelines
      -a pilot study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Increasing evidence indicates that sex-specific
      issues may have impact on prevention, diagnosis, or treatment. These issues are
      not systematically considered during the development of Dutch clinical practice
      guidelines. The aim of this study is to identify how members of guideline
      development groups discuss sex-specific evidence, and whether and how the
      outcomes of these discussions are reflected in the guideline. METHODS: Six
      guideline development committees (GDCs) were studied. Each committee was
      supported by a staff member from the guideline organization who was trained and
      received feedback to facilitate uptake of evidence on sex differences in the
      process of guideline development. Non-participant observation and transcription
      of audio recordings from 22 GDC meetings were performed. Content analysis of
      meeting transcripts and guidelines were studied to analyse characteristics of
      discussion episodes on sex-specific research data-based issues (subject matter,
      initiator and group approach towards the topic and themes) and whether or not
      conclusions on evidence were reflected in the final guideline text. RESULTS: Of
      the 87 identified discussion episodes, 68 dealt with sex-specific research
      evidence potentially relevant to guidelines. Respectively 51%, 28% and 21% of the
      latter episodes were initiated by committee members, staff members and
      chairpersons. Group approaches towards the subject matter were generally
      positive. Data from 60% of those episodes were reflected in the final guideline
      text. Sex-specific data on reproductive issues were more often discussed and
      reflected in guideline texts than data on other health issues. Discussion
      episodes on sex-specific evidence initiated by chairpersons were most often
      reflected in the guidelines. CONCLUSIONS: This pilot study indicates that GDCs
      regularly focused on sex-specific issues. The participation of a trained staff
      member contributed to this.

PMID- 21091854
TI  - Vitality predicts level of guideline-concordant care in routine treatment of
      mood, anxiety and somatoform disorders.
AB  - OBJECTIVE: To examine the clinical and psychosocial correlates of adherence to
      treatment guidelines among outpatients with common mental disorders in a routine
      clinical setting. METHODS: In this retrospective cohort study, we analysed 192
      patients who were treated for a mood, anxiety or somatoform disorder with
      pharmacotherapy, psychotherapy or a combination of both treatment modalities.
      Guideline adherence was assessed with a disorder independent set of quality
      indicators during up to 3 years of follow-up. At baseline, a standardized
      diagnostic interview, the Brief Symptom Inventory (BSI), the Short Form 36 (SF
      36) and demographic variables were assessed. Using multivariable regression
      analysis we identified independent predictors associated with guideline
      adherence. RESULTS: Patients were aged 36.8 years (SD 11.6) on average. The
      majority of patients were treated with psychotherapy (47.4%), followed by
      pharmacotherapy (37.5%) and a combination of pharmacotherapy and psychotherapy
      (15.1%). Three adherence groups were defined: low (29.7%), intermediate (43.2%)
      and high (27.1%). Univariate predictors of low adherence were low scores on the
      subscales vitality and social functioning of the SF-36. In the multivariable
      model, low adherence was independently predicted by a score lower than 50 on the
      subscale vitality of the SF-36 (odds ratio per 10 units increase in vitality =
      1.34, 95% confidence interval: 1.06-1.71). No significant differences were found
      within socio-demographic variables, co-morbidity and the scores on the BSI
      subscales between the adherence groups. CONCLUSIONS: We found that patients with
      low scores on the vitality subscale of the SF-36 were at the highest risk to
      receive low guideline-concordant care. Understanding factors that affect
      treatment adherence may help to prevent non-adherence and increase the quality of
      care as well as cost-effectiveness.

PMID- 21091855
TI  - Consultation behaviour of doctor-shopping patients and factors that reduce
      shopping.
AB  - RATIONALE, AIMS AND OBJECTIVES: To investigate the subsequent behaviour of doctor
      shopping patients (defined as those attending multiple hospitals for the same
      complaint) who consulted our department and factors related to cessation of
      doctor shopping. METHODS: Patients who presented without referral to the
      Department of General Medicine at Chiba University Hospital in Japan (our
      department) completed a questionnaire at their first visit. A follow-up
      questionnaire was also sent to them in order to assess doctor shopping after 3
      months. Then items in the questionnaires were investigated for significant
      differences between patients who continued or stopped doctor shopping. Logistic
      regression analysis was performed with items showing a significant difference
      between patients who stopped doctor shopping and those who continued it, in order
      to identify independent determinants of the cessation of shopping. RESULTS: A
      total of 978 patients who presented spontaneously to our department consented to
      this study, and 929 patients (95.0%) completed questionnaires correctly. Among
      them, 203 patients (21.9%) were identified as doctor shoppers. The follow-up
      survey was completed correctly by 138 patients (68.0%). Among them, 25 patients
      (18.1%) were found to have continued doctor shopping, which was a significantly
      lower rate than before (P < 0.001). Logistic regression analysis selected the
      following factors as independent determinants of the cessation of doctor
      shopping: 'confirmation of the diagnosis' (odds ratio: 8.12, 95% confidence
      interval: 1.46-45.26), and 'satisfaction with consultation' (odds ratio: 2.07,
      95% confidence interval: 1.42-3.01). CONCLUSION: Doctor shopping decreased
      significantly after patients consulted our department, with 'confirmation of the
      diagnosis' and 'satisfaction with consultation' being identified as contributing
      factors.

PMID- 21091856
TI  - Disease profile of children under 5 years attending primary health care clinics
      in a high HIV prevalence setting in South Africa.
AB  - OBJECTIVE: To describe the presenting complaints and disease profile of children
      attending primary health care (PHC) clinics in two provinces of South Africa.
      METHODS: Participants were sick children 2-59 months old presenting for care at
      PHC clinics in KwaZulu-Natal (KZN) and Limpopo provinces from 2006-2007. Children
      were assessed by an expert Integrated Management of Childhood Illnesses (IMCI)
      practitioner. Children for whom parental/guardian consent was obtained were
      tested for HIV. RESULTS: A total of 1357 children attending one of 74 clinics
      were assessed. HIV seroprevalence overall was 7.1%, but was significantly higher
      in KZN than Limpopo (7.5 vs. 2.4%; OR = 3.3, 95%CI 1.9-5.8%). Commonest
      presenting complaints were cough (72%), skin conditions (22%) and diarrhoea
      (19%). Of 1349 children, 120 (8.9%) had a weight below the third percentile;
      108/1357 (8.0%) children required urgent referral, most commonly for severe
      pneumonia (53.7%) and severe malnutrition (16.7%). In multivariate analyses,
      severe pneumonia, growth faltering and urgent referral were independently
      associated with younger age, residence in KZN and HIV infection (P < 0.05).
      CONCLUSIONS: Many children with severe illnesses and undiagnosed HIV infection
      present to PHC facilities. PHC staff require skills to correctly manage these
      conditions and undertake HIV testing. Although IMCI provides evidence-based
      guidelines, implementation must be improved to achieve adequate coverage of life
      saving interventions.

PMID- 21091857
TI  - Role of risk factors and socio-economic status in pulmonary tuberculosis: a
      search for the root cause in patients in a tertiary care hospital, South India.
AB  - OBJECTIVE: To determine the frequency of underlying risk factors and the socio
      economic impact based on occupation in the development of tuberculosis. METHOD:
      Retrospective analysis of 207 clinically and microbiologically diagnosed patients
      with pulmonary tuberculosis (PTB) admitted to Kasturba Hospital in 2005 and 2006.
      Demographic details and underlying risk factors were statistically evaluated.
      RESULTS: Diabetes mellitus (DM) (30.9%) was the most prevalent condition and
      significantly more common than other risk factors like smoking (16.9%),
      alcoholism (12.6%), HIV (10.6%), malignancy (5.8%), chronic liver diseases
      (3.9%), history of contact with TB (3.4%), chronic corticosteroid therapy (2.9%),
      chronic kidney diseases and malnourishment (1.5%). There were 82 patients (39.6%)
      with no underlying risk factor. Men (M:F = 3.7:1) and patients older than 40
      years had a higher incidence of co-existing conditions. PTB was significantly
      more common in blue-collar (44%) and white-collar (27.1%) workers than household
      workers (12.1%), students (10.6%) and retired/unemployed people (6.3%).
      CONCLUSION: Pulmonary tuberculosis had a significant impact and predominated in
      male patients co-existing with DM. Patients with DM and suggestive pulmonary
      symptoms should be screened for tuberculosis. More stringent health education and
      awareness programme should be implemented at the grass root level.

PMID- 21091858
TI  - Bacterial hand contamination among Tanzanian mothers varies temporally and
      following household activities.
AB  - OBJECTIVE: To characterize mechanisms of hand contamination with faecal indicator
      bacteria and to assess the presence of selected pathogens on mothers' hands in
      Tanzania. METHODS: A household observational study combined with repeated
      microbiological hand rinse sampling was conducted among 119 mothers in Dar es
      Salaam, Tanzania. All hand rinse samples were analysed for enterococci and
      Escherichia coli, and selected samples were analysed for genetic markers of
      Bacteroidales, enterovirus and pathogenic E. coli. RESULTS: Using the toilet,
      cleaning up a child's faeces, sweeping, cleaning dishes, preparing food and
      bathing were all found to increase faecal indicator bacterial levels on hands.
      Geometric mean increases in colony forming units per two hands ranged from 50
      (cleaning dishes) to 6310 (food preparation). Multivariate modelling of hand
      faecal indicator bacteria as a function of activities recently performed shows
      that food handling, exiting the household premises and longer time since last
      handwashing with soap are positively associated with bacterial levels on hands,
      while bathing is negatively associated. Genetic markers of Bacteroidales,
      enterovirus and pathogenic E. coli were each detected on a subset of mothers'
      hands. CONCLUSIONS: Escherichia coli and enterococci on hands can be
      significantly increased by various household activities, including those
      involving the use of soap and water. Thus, faecal indicator bacteria should be
      considered highly variable when used as indicators of handwashing behaviour. This
      work corroborates hands as important vectors of disease among Tanzanian mothers
      and highlights the difficulty of good personal hygiene in an environment
      characterized by the lack of networked sanitation and water supply services.

PMID- 21091859
TI  - Prevalence and self-reported health consequences of vaginal practices in KwaZulu
      Natal, South Africa: findings from a household survey.
AB  - OBJECTIVES: To investigate population-level prevalence of vaginal practices,
      their frequency and self-reported health consequences in KwaZulu-Natal, South
      Africa. METHODS: A household survey using multi-stage cluster sampling was
      conducted in 2007. Women aged 18-60 (n = 867) were interviewed on demographics,
      sexual behaviours and vaginal practices, focusing on intravaginal practices.
      Design-based analysis used multivariate logistic regression to identify factors
      associated with intravaginal or any practice. RESULTS: Most women currently
      perform vaginal practices (90.2%), with 34.8% reporting two and 16.3%>=3
      practices. Internal cleansing, the commonest practice (63.3% of women), is
      undertaken frequently (61.6% cleansing twice daily; 20.0% using >=2 products).
      Fewer report application (10.1%), insertion (11.6%) or ingestion (14.3%)
      practices. Hygiene is a common motivation, even for the 23.2% of women reporting
      intravaginal practices around the time of sex. Prevalence of any practice was
      lower among women with tertiary education than those without primary education
      (AOR = 0.26, 95% CI = 0.08-0.85), nearly twice as common in sexually active women
      (95% CI = 1.05-3.56) and increased as overall health status declined. Adjusted
      odds of intravaginal practices were 1.8-fold higher in women reporting
      unprotected sex (95% CI = 1.11-2.90). Few reported health problems with current
      practices (0.6%); though, 12.6% had ever-experienced adverse effects.
      CONCLUSIONS: Vaginal practices are common in KwaZulu-Natal. Although self
      reported health problems with current practices are rare, high lifetime risk of
      adverse events and potential for asymptomatic but clinically important damage
      make continued research important.

PMID- 21091861
TI  - Broad-range antagonistic rhizobacteria Pseudomonas fluorescens and Serratia
      plymuthica suppress Agrobacterium crown gall tumours on tomato plants.
AB  - AIM: To examine the biocontrol activity of broad-range antagonists Serratia
      plymuthica IC1270, Pseudomonas fluorescens Q8r1-96 and P. fluorescens B-4117
      against tumourigenic strains of Agrobacterium tumefaciens and A. vitis. METHODS
      AND RESULTS: Under greenhouse conditions, the antagonists, applied via root soak
      prior to injecting Agrobacterium strains into the wounded stems, significantly
      suppressed tumour development on tomato seedlings. A derivative of P. fluorescens
      Q8r1-96 tagged with a gfp reporter, as well as P. fluorescens B-4117 and S.
      plymuthica IC1270 marked with rifampicin resistance, stably persisted in tomato
      tissues for at least 1 month. Mutants of P. fluorescens Q8r1-96 and S. plymuthica
      IC1270 deficient in 2,4-diacetylphloroglucinol or pyrrolnitrin production,
      respectively, also proficiently suppressed the tumour development, indicating
      that these antibiotics are not responsible for the observed biocontrol effect on
      crown gall disease. The volatile organic compounds (VOCs) produced by the tested
      P. fluorescens and S. plymuthica strains inhibited the growth of A. tumefaciens
      and A. vitis strains in vitro. Solid-phase microextraction-gas chromatography
      mass spectrometry analysis revealed dimethyl disulfide (DMDS) as the major
      headspace volatile produced by S. plymuthica IC1270; it strongly suppressed
      Agrobacterium growth in vitro and was emitted by tomato plants treated with S.
      plymuthica IC1270. 1-Undecene was the main volatile emitted by the examined P.
      fluorescens strains, with other volatiles, including DMDS, being detected in only
      relatively low quantities. CONCLUSIONS: S. plymuthica IC1270, P. fluorescens B
      4117 and P. fluorescens Q8r1-96 can be used as novel biocontrol agents of
      pathogenic Agrobacterium. VOCs, and specifically DMDS, might be involved in the
      suppression of oncogenicity in tomato plants. However, the role of specific
      volatiles in the biocontrol activity remains to be elucidated. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The advantage of applying these antagonists lies in their
      multiple activities against a number of plant pathogens, including Agrobacterium.

PMID- 21091863
TI  - The PprA-PprB two-component system activates CupE, the first non-archetypal
      Pseudomonas aeruginosa chaperone-usher pathway system assembling fimbriae.
AB  - The opportunistic pathogen Pseudomonas aeruginosa has redundant molecular systems
      that contribute to its pathogenicity. Those assembling fimbrial structures
      promote complex organized community lifestyle. We characterized a new 5.8 kb
      genetic locus, cupE, that includes the conserved usher- and chaperone-encoding
      genes. This locus, widely conserved in different bacterial species, contains four
      additional genes encoding non-archetypal fimbrial subunits. We first evidenced
      that the cupE gene cluster was specifically expressed in biofilm conditions and
      was responsible for fibre assembly containing at least CupE1 protein, at the
      bacterial cell surface. These fimbriae not only played a significant role in the
      early stages (microcolony and macrocolony formation) but also in shaping 3D
      mushrooms during P. aeruginosa biofilm development. Using wide-genome transposon
      mutagenesis, we identified the PprAB two-component system (TCS) as a regulator of
      cupE expression, and further demonstrated the involvement of the PprAB TCS in
      direct CupE fimbrial assembly activation. Thus, this TCS represents a new
      regulatory element controlling the transition between planktonic and community
      lifestyles in P. aeruginosa.

PMID- 21091862
TI  - Expression of virulence genes in luminescent and nonluminescent isogenic vibrios
      and virulence towards gnotobiotic brine shrimp (Artemia franciscana).
AB  - AIMS: This study aimed to evaluate the expression levels of virulence gene
      regulators (luxR and toxR) and virulence factors (serine protease,
      metalloprotease and haemolysin) in luminescent and nonluminescent isogenic Vibrio
      harveyi and Vibrio campbellii. METHOD AND RESULTS: Nonluminescent variants have
      been reported before to become dominant in cultures of luminescent vibrios when
      grown under static conditions in the dark. Wild-type V. harveyi BB120, V.
      campbellii LMG 21363, quorum sensing mutants of V. harveyi BB120 and their
      previously reported nonluminescent isogenic counterparts were used in this study.
      The expression level of the virulence genes srp serine protease, vhp
      metalloprotease and vhh haemolysin, the quorum sensing master regulator gene luxR
      and the virulence regulator gene toxR in isogenic luminescent and nonluminescent
      strains were quantified using reverse transcriptase real-time PCR. These
      experiments revealed that the nonluminescent strains produced lower levels of the
      quorum sensing master regulator gene luxR and the vhp metalloprotease gene (which
      is known to be regulated by quorum sensing). Finally, challenge tests with
      gnotobiotic brine shrimp (Artemia franciscana) larvae revealed that the
      nonluminescent strains are less virulent than their luminescent isogenic
      counterparts. CONCLUSION: Nonluminescent variants of V. harveyi and V. campbellii
      strains produce lower levels of the quorum sensing master regulator gene luxR and
      the vhp metalloprotease gene and are less virulent to brine shrimp than their
      isogenic luminescent counterparts. SIGNIFICANCE AND IMPACT OF THE STUDY: These
      results indicate that adaptation of luminescent vibrios to specific growth
      conditions that result in a dominant nonluminescent phenotype is accompanied by a
      decreased adaptation to a host environment because of altered virulence gene
      regulation.

PMID- 21091860
TI  - Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA
      pharmacogenetic substudy of DART.
AB  - OBJECTIVES: To determine the frequencies of HLA-B alleles in Ugandan patients in
      the NORA substudy of the DART trial and to compare HLA-B allele frequencies in
      those with and without clinically diagnosed hypersensitivity reaction (HSR).
      METHODS: DNA-based HLA-B genotyping was used to determine HLA alleles in 247
      participants who received abacavir, including all six participants ('cases') with
      clinically diagnosed abacavir HSR. RESULTS: The incidence of clinical abacavir
      HSR in this double-blinded study was 2.0% (6/300) in the abacavir group. As HLA
      B*5701 was absent throughout the entire cohort, including the six HSR 'cases', an
      association could not be established between HLA-B*5701 and clinically diagnosed
      abacavir HSR. No other HLA-B*57 alleles were present among the six 'cases'. HLA
      B*5703 was the most frequent HLA-B*57 allele among the abacavir-tolerant
      participants. CONCLUSION: The rate of clinical HSR was low, which may reflect the
      expected 2-3% clinical false-positive rate seen in previous double-blind
      randomized studies. The presumption that these cases may be false-positive
      abacavir HSR is supported by the fact that no HLA-B*5701 alleles were found in
      the abacavir group. Implementation of prospective HLA-B*5701 screening must be
      based on benefit/risk considerations within local practice. Clinical risk
      management remains paramount.

PMID- 21091864
TI  - Modelling sugar diffusion across plant leaf cuticles: the effect of free water on
      substrate availability to phyllosphere bacteria.
AB  - We present a continuous model for the diffusion of sugars across intact plant
      leaf cuticles. It is based on the flow of sugars from a source, representing the
      leaf apoplast, to a sink, in the shape of a hemispherical drop of water on the
      outside of the cuticle. Flow is a function of the difference between sugar
      concentrations C(Source) and C(Sink) , permeability P of the cuticle, volume
      V(Sink) of the water drop, as well as its contact angle alpha with the cuticle
      surface. Using a bacterial bioreporter for fructose, and a two-compartment
      experimental set-up consisting of isolated cuticles of walnut (Juglans regia)
      carrying water droplets while floating on solutions with increasing
      concentrations of fructose, we determined a value of 1 * 10-6 m h-1 for P. Using
      this value, we explored different scenarios for the leaching of sugars across
      plant leaf cuticles to reveal in quantitative terms how diffusion takes longer
      when V(Sink) increases, P decreases or alpha increases. Bacterial growth was
      modelled as a function of changes in P, alpha and V(Sink) and was consistent with
      observations or suggestions from the literature in relation to the availability
      of free water on leaves. These results are discussed in the light of bacteria as
      ecosystem engineers, i.e. with the ability to modify the plant leaf surface
      environment in favour of their own survival, e.g. by increasing cuticle leakage
      or leaf wetness. Our model represents a first step towards a more comprehensive
      model which will enhance our quantitative understanding of the factors that play
      a role in nutrient availability to bacterial colonizers of the phyllosphere, or
      plant leaf surface.

PMID- 21091865
TI  - Assessment of thrombin generation measured before and after cardiopulmonary
      bypass surgery and its association with postoperative bleeding.
AB  - BACKGROUND: Bleeding after cardiopulmonary bypass (CPB) is a major cause of
      morbidity and mortality and consumes large amounts of blood. Identifying patients
      at increased risk of bleeding secondary to hemostatic impairment may improve
      clinical outcomes by allowing early intervention. METHODS: This present study
      recruited 77 patients undergoing CPB and measured coagulation screens,
      coagulation factors, TEG((r)), Rotem((r)) and thrombin generation (TG) before
      surgery and 30 min after heparin reversal. The tests were analyzed to investigate
      whether they identified patients at increased risk of excess bleeding (defined as
      > 1000 mL) in the first 24 h postoperatively. RESULTS: Patients who bled > 1000
      mL had a lower: platelet count (P < 0.02), factors (F)IX, X and XI (P < 0.005),
      endogenous thrombin potential (ETP) and an initial rate of TG (P < 0.02) and
      higher activated partial thromboplastin time (aPTT) (P < 0.001) than patients who
      bled < 1000 mL. Receiver operating characteristic (ROC) analysis was significant
      for post-operative TG and aPTT (P < 0.001). Furthermore, reduced pre-operative TG
      was associated with increased postoperative bleeding (P < 0.02). Pre- and
      postoperative TG were correlated (rho = 0.7, P < 0.001). TEG((r)), Rotem((r)) and
      prothrombin time (PT) at either time point were not associated with increased
      bleeding. CONCLUSION: These data suggest that pre-operative defects in the
      propagation phase of hemostasis are exacerbated during CPB, contributing to
      bleeding post-CPB. TG taken both pre- and postoperatively could potentially be
      used to identify patients at an increased risk of bleeding post-CPB.

PMID- 21091866
TI  - The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude
      pulmonary embolism.
AB  - BACKGROUND: The Pulmonary Embolism Rule-out Criteria (PERC) rule is a clinical
      diagnostic rule designed to exclude pulmonary embolism (PE) without further
      testing. We sought to externally validate the diagnostic performance of the PERC
      rule alone and combined with clinical probability assessment based on the revised
      Geneva score. METHODS: The PERC rule was applied retrospectively to consecutive
      patients who presented with a clinical suspicion of PE to six emergency
      departments, and who were enrolled in a randomized trial of PE diagnosis.
      Patients who met all eight PERC criteria [PERC((-))] were considered to be at a
      very low risk for PE. We calculated the prevalence of PE among PERC((-)) patients
      according to their clinical pretest probability of PE. We estimated the negative
      likelihood ratio of the PERC rule to predict PE. RESULTS: Among 1675 patients,
      the prevalence of PE was 21.3%. Overall, 13.2% of patients were PERC((-)). The
      prevalence of PE was 5.4% [95% confidence interval (CI): 3.1-9.3%] among PERC((
      )) patients overall and 6.4% (95% CI: 3.7-10.8%) among those PERC((-)) patients
      with a low clinical pretest probability of PE. The PERC rule had a negative
      likelihood ratio of 0.21 (95% CI: 0.12-0.38) [corrected] for predicting PE
      overall, and 0.63 (95% CI: 0.38-1.06) in low-risk patients. CONCLUSIONS: Our
      results suggest that the PERC rule alone or even when combined with the revised
      Geneva score cannot safely identify very low risk patients in whom PE can be
      ruled out without additional testing, at least in populations with a relatively
      high prevalence of PE.

PMID- 21091867
TI  - No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function
      in patients with schizophrenia and bipolar disorder.
AB  - The Disrupted-in-Schizophrenia-1 (DISC1) gene has been implicated in both
      schizophrenia and bipolar disorder by linkage and genetic association studies.
      Altered prefrontal cortical function is a pathophysiological feature of both
      disorders, and we have recently shown that variation in DISC1 modulates
      prefrontal activation in healthy volunteers. Our goal was to examine the
      influence of the DISC1 polymorphism Cys704Ser on prefrontal function in
      schizophrenia and bipolar disorder. From 2004 to 2008, patients with
      schizophrenia (N = 44), patients with bipolar disorder (N = 35) and healthy
      volunteers (N = 53) were studied using functional magnetic resonance imaging
      while performing a verbal fluency task. The effect of Cys704Ser on cortical
      activation was compared between groups as Cys704 carriers vs. Ser704 homozygotes.
      In contrast to the significant effect on prefrontal activation we had previously
      found in healthy subjects, no significant effect of Cys704Ser was detected in
      this or any other region in either the schizophrenia or bipolar groups. When
      controls were compared with patients with schizophrenia, there was a diagnosis by
      genotype interaction in the left middle/superior frontal gyrus [family-wise error
      (FWE) P = 0.002]. In this region, Ser704/ser704 controls activated more than
      Cys704 carriers, and there was a trend in the opposite direction in schizophrenia
      patients. In contrast to its effect in healthy subjects, variation in DISC1
      Cys704Ser704 genotype was not associated with altered prefrontal activation in
      patients with schizophrenia or bipolar disorder. The absence of an effect in
      patients may reflect interactions of the effects of DISC1 genotype with the
      effects of other genes associated with these disorders, and/or with the effects
      of the disorders on brain function.

PMID- 21091868
TI  - Impaired striatum-dependent behavior in GASP-1-knock-out mice.
AB  - G protein-coupled receptor (GPCR) associated sorting protein-1 (GASP-1) is
      suspected to play a key role in recycling and degradation of several GPCRs. In a
      previous study, we have shown that GASP-1-knock-out (GASP-1-KO) mice displayed
      deficits in acquiring a cocaine self-administration task, associated with an
      exacerbated down-regulation of striatal dopaminergic and cholinergic receptors.
      Among several possibilities, GASP-1 deficiency could have impaired memory
      processes underlying the acquisition of the operant conditioning task. Therefore,
      the present study investigated cognitive performances of GASP-1-KO mice and their
      wild-type littermates (WT) in a broad variety of memory tasks. Consistent with a
      deficit in procedural memory, GASP-1-KO mice showed delayed acquisition of a food
      reinforced bar-press task. During water-maze training in hidden- or visible
      platform paradigms, mutant and WT mice acquired the tasks at the same rate.
      However, GASP-1 mice exhibited persistent thigmotaxic swimming, longer distance
      to the platform, and reduced swim speed. There was no deficit in several tasks
      requiring simple behavioral responses (Barnes maze, object recognition and
      passive avoidance tasks). Thus, the ability to acquire and/or express complex
      responses seems affected in GASP-1-deficient mice. Hippocampal functions were
      preserved, as the retention of an acquired memory in spatial tasks remained
      unaffected. The pattern of behavioral deficits observed in GASP-1-KO mice is
      coherent with current knowledge on the role of striatal GPCRs in
      acquisition/expression of skilled behavior and in motivation. Together with the
      previous findings, the so far established phenotype of GASP-1-KO mice makes them
      a potentially exciting tool to study striatal functions.

PMID- 21091869
TI  - Update dermatologic laser therapy.
AB  - New trends in dermatological laser therapy during the last years are based on new
      wavelengths, concepts and treatment combinations resulting in a variety of new
      dermatologic indications. Fractional laser therapy of chronic actinic damage of
      the skin has been introduced and already represents a standard technique. The
      concept of fractional non-ablative and ablative laser treatment has been shown to
      be safe and effective. Also pigmented and vascular skin changes can be treated by
      this method. New, very promising concepts for laser epilation include linear
      scanned as well as low fluence laser systems. The first enable very short
      treatment times for large areas; the latter are the basis for the growing market
      of laser epilation devices for home use. Nevertheless, the potential of low
      fluence laser devices for long-term hair reduction has not been tested so far.
      Furthermore, no data exist on side effects resulting from repetitive application
      of laser light to melanocytic lesions. Laser lipolysis has been introduced as the
      latest, minimally invasive way of removing small localised fat deposits. The new
      procedure may have a great potential for liposculpture; its further development
      should be thoughtfully observed. The latest innovations for precise ablation are
      ultra-short pulsed laser systems. Femtosecond lasers avoid thermal damage at the
      border areas of ablation zones.

PMID- 21091870
TI  - Chondrodermatitis nodularis chronica helicis - a conservative therapeutic
      approach by decompression.
AB  - BACKGROUND: Chondrodermatitis nodularis chronica helicis is a rather common
      condition which substantially affects quality of life causing pain and sleeping
      disturbances. Surgical treatment is connected with a tendency to recurrence.
      Mechanical pressure is probably the main etiological factor. PATIENTS AND
      METHODS: A prospective study was performed with 18 patients that were offered a
      non-surgical treatment using a self-made bandage of foam plastic which they
      applied during the night. Of these, 12 performed the treatment including follow
      up; 6 patients initially also consented, but they did not return after the
      initial visit. RESULTS: 11 patients reported substantial reduction of pain within
      the first month; after an average of 1.75 months they were free of pain. All 8
      patients with initial sleeping problems caused by pain reported undisturbed sleep
      after only one month. In 11 patients the lesions receded satisfactorily, in 9
      patients completely, in 2 patients leaving small asymptomatic residual lesions.
      Recurrences appeared in 3 patients with 2 of them having been surgically
      pretreated at the same location. CONCLUSIONS: We recommend conservative treatment
      using protective padding as first line treatment for chondrodermatitis nodularis
      chronica helicis. The successful outcome achieved only by relief of pressure
      supports pressure as the main etiological factor in the development of the
      disease.

PMID- 21091871
TI  - Quick and effective treatment of small neurofibromas.

PMID- 21091872
TI  - Surgical treatment of severe palmoplantar keratoderma.

PMID- 21091873
TI  - Ultrasound guidance for central venous catheter placement in Australasian
      emergency departments: potential barriers to more widespread use.
AB  - OBJECTIVES: To survey Fellows of the Australasian College for Emergency Medicine
      (FACEMs) in order to describe current ultrasound (US) usage during central venous
      catheter (CVC) placement and to compare practice and opinions between FACEMs
      routinely using US and those not. METHODS: Descriptive and analytical cross
      sectional electronic survey of all FACEMs. Baseline variables including hospital
      type, US availability, frequency of CVC insertion, US usage and technique are
      presented descriptively. US practice and opinions on usage are compared between
      routine and non-routine users. RESULTS: Responses were obtained from 486 (42.4%)
      of 1146 FACEMs emailed. Whereas 88.5% of respondents had US available and 70% had
      done an US course, only 37% routinely used US for CVC placement. Completion of an
      US course and performance of >11 CVC per year were strongly associated with
      routine US use (odds ratio 10.0 [5.5-18.4] and 2.6 [1.7-3.9], respectively).
      Common barriers to more frequent US use were not having completed an US course
      (20%) and US-guided CVC placement taking too long (18%). Eighty-five per cent of
      FACEMs agreed that there should be ED access to US and US training but only 34%
      thought its use should be mandatory. CONCLUSIONS: We found that only 37% of FACEM
      respondents routinely used US to guide placement of CVCs and a number of barriers
      to more frequent use are identified. Practices and opinions regarding US use
      differed significantly between routine and non-routine users.

PMID- 21091874
TI  - Variation in the management of hypothetical cases of acute agitation in
      Australasian emergency departments.
AB  - OBJECTIVE: To describe the prescribing practice of emergency medicine clinicians
      in the management of highly agitated patients and to identify perceived barriers
      to management and the gaps in training. METHOD: We undertook an anonymous cross
      sectional mail survey of the Australasian College for Emergency Medicine (ACEM)
      members (fellows and advanced trainees) between June and September 2009. A
      questionnaire including a case vignette of a hypothetical patient and three
      clinical scenarios was employed to ascertain prescribing practice and assess
      perceived barriers to management, confidence and the perceived usefulness of
      existing and future Clinical Practice Guidelines (CPGs). RESULTS: All 2052 ACEM
      members were surveyed. However, seven had incorrect postal addresses and could
      not be reached. Of the remaining 2045, 786/2052 (38.3%, 95% CI 36.2-40.5)
      responses were received. Of the 786 respondents, 783 were practicing clinicians.
      If monotherapy was chosen, 622/783 (79.4%, 95% CI 76.4-82.2) of respondents
      preferred midazolam to manage the common scenario where no history was available,
      followed by haloperidol 45/783 (5.8%, 95% CI 4.3-7.7) and olanzapine 38/783
      (4.9%, 95% CI 3.5-6.7). Most respondents 500/783 (63.9%, 95% CI 60.4-67.2) would
      also administer another sedative (combination therapy). Important perceived
      barriers to agitation management included lack of both training (352/783 [45.0%,
      95% CI 41.4-48.5]) and a national CPG (313/783 [40.0%, 95% CI 36.5-43.5]).
      Respondents were generally confident in all aspects of management, although
      relatively fewer trainees were confident in determining dosing. Institutional
      CPGs were considered most useful for 415/783 (53.0%, 95% CI 49.4-56.5)
      respondents. If an ACEM-endorsed CPG were to be developed in the future, 634/783
      (81.0%, 95% CI 78.0-83.6) respondents would consider this useful. CONCLUSION:
      There is considerable variation in the management of hypothetical cases of acute
      agitation in Australasian EDs. Benzodiazepines and antipsychotics, either alone
      or in combination, are commonly used. An ACEM-endorsed, Australasian CPG was
      perceived as useful.

PMID- 21091875
TI  - How willing are men who have sex with men in China to be circumcised for the sake
      of protecting his female sex partner?
AB  - INTRODUCTION: The HIV prevalence among men who have sex with men (MSM) is
      increasing sharply in China. Many MSM have female sexual partners, representing a
      bridge of transmitting HIV to the general population. Circumcision reduces the
      risk of HIV prevention via heterosexual intercourse. AIM: The study investigated
      the prevalence and factors related to willingness to undergo circumcision when
      MSM were informed that circumcision could reduce risk of heterosexual HIV
      transmission. METHODS: An anonymous cross-sectional survey was conducted in
      Jiangsu, China. A total of 157 MSM with bisexual behaviors in the last six months
      were recruited using snowball sampling. MAIN OUTCOME MEASURES: Self-reported
      circumcision status and foreskin conditions were recorded. HIV-related knowledge,
      risk perceptions, risky sexual behaviors, cognitive and behavioral intention
      factors regarding circumcision were assessed. RESULTS: Among all respondents,
      5.7% were circumcised. In the uncircumcised subsample, the willingness to be
      circumcised increased from 8.1% to 35.1% after they were informed about the 50%
      risk reduction effect of circumcision regarding heterosexual HIV transmission.
      Risk behaviors, uncertainty about the prevalence of HIV among MSM, perception of
      overly long foreskin, peer's suggestion, disagreement with the statements "MSM in
      general are not willing to be circumcised" and "circumcisions are for children,
      not for adults" and self-efficacy for circumcision were significantly associated
      with willingness for circumcision given the hypothetical risk reduction effect
      (OR = 2.37 and 3.11, respectively, P < 0.05). Perception of overly long foreskin,
      self-efficacy, and having used a condom in the last episode of sex with a woman
      remained significantly associated with the conditional willingness for
      circumcision in the multivariate analysis (OR = 3.03, 2.84 and 2.42,
      respectively, P < 0.05). CONCLUSIONS: Interventions promoting circumcision among
      bisexual MSM, based on the risk reduction effect on heterosexual HIV
      transmission, are likely to be successful. Such programs should focus on
      increasing self-efficacy and may consider utilizing a peer educator approach.

PMID- 21091876
TI  - Sexual dysfunction--a silent hurt: issues on treatment awareness.
AB  - BACKGROUND: The magnitude of sexual health problems and availability of treatment
      options in the local environment is yet to be documented; thus, there is an
      urgent need for this, as sexual dysfunction may be a real social and
      psychological problem, needing urgent attention. OBJECTIVE: The aim of this study
      was to investigate the prevalence of sexual dysfunction and pattern of sexual
      health seeking behavior, among secondary school teachers in Ilorin, Kwara State
      Nigeria. METHODS: 450 teachers were invited to complete an anonymous self
      administered sociodemographic questionnaire, as well as three other instruments
      measuring human sexuality and general mental health status. MAIN OUTCOME
      MEASURES: The survey instrument used were the International Index of Erectile
      Function (IIEF-5), a modified Sexual Activity Questionnaire (SAQ), and the
      General Health Questionnaire -30 (GHQ -30). Result were compared with established
      normative data, and validated cut-off scores that were available. RESULTS: A
      total of 417 teachers (93%) responded to the questionnaire. The following
      prevalence rates were found: female anorgasmia (40%), lubrication failure (30%),
      dyspareunia (12%), erectile dysfunction, premature ejaculation and male orgasmic
      disorder (23% each), loss of sexual desire (24%), sexual life dissatisfaction,
      and relationship dissatisfaction six months prior to interview (10% each), and
      GHQ-30 scores were significant in sexual dysfunction in both genders, except for
      female anorgasmia and premature ejaculation in males. However, a presence of
      psychiatric morbidity was significantly found in overall sexual life
      dissatisfaction, as well as relationship dissatisfaction. The pattern of sexual
      health help-seeking behavior showed that majority (53%) do not seek treatment. Of
      these 53%, many (44%) gave the reason that they thought it transient, ignorance
      of hospital treatment service (30%), and fear of stigma (26%); also, among those
      that sought treatment, 46% chose alternative medicine. CONCLUSION: The prevalence
      of sexual dysfunctions found in this study is comparable to those reported in
      earlier Nigerian studies. Despite this and the significant "psychiatric
      morbidity" experienced in sexual difficulties, apparently no health services have
      been specially designed to address sexual dysfunction among the teacher's group
      or the general population at large. This study therefore draws urgent attention
      to the need for services geared towards alleviating sexual problems, more
      professional and patient education are recommended.

PMID- 21091877
TI  - Sexual function during long-term duloxetine treatment in patients with recurrent
      major depressive disorder.
AB  - INTRODUCTION: Sexual dysfunction (SD) is frequently associated with major
      depressive disorder (MDD) in the untreated state and may be worsened by
      antidepressant treatment. AIM: We evaluated SD in duloxetine-treated patients
      during an MDD recurrence prevention study. METHOD: Patients (N = 514) received
      open-label duloxetine 60-120 mg/day for up to 34 weeks. Responders (N = 288) were
      randomly assigned to duloxetine or placebo during a further 52-week double-blind
      maintenance phase. MAIN OUTCOME MEASURES: The Arizona Sexual Experience Scale
      (ASEX) was used to assess sexual functioning. RESULTS: At study entry, 73.4% of
      patients met ASEX criteria for SD. After open-label duloxetine treatment, the
      probability of continued SD was 77.9% for nonresponders and 53.2% for responders.
      In patients without SD at study entry, the probability of emergent SD was 49.6%
      (nonresponders) and 33.2% (responders). In the double-blind maintenance phase,
      there was no significant difference (P = 0.105) in the probability of emergent SD
      between placebo-treated (49.2%) and duloxetine-treated (27.9%) patients without
      SD at baseline, with no significant treatment-by-gender interaction. In patients
      with a recurrence of MDD, the probability of emergent SD was similar between
      placebo- (71.3%) and duloxetine-treated (82.7%) patients. However, in patients
      with no recurrence of MDD, the probability of emergent SD in placebo patients
      (40.0%) was numerically higher than in duloxetine patients (12.9%). Spontaneous
      reports of adverse events related to sexual function were infrequent and no
      patients discontinued due to these events. CONCLUSIONS: In patients with MDD, the
      probability of continued or emergent SD after up to 34 weeks of open-label
      duloxetine treatment was associated with the response status of the patients. In
      patients who responded to duloxetine treatment, after up to a further 52 weeks of
      double-blind treatment either with duloxetine or placebo, the probability of
      continued or emergent SD appeared to be more related to MDD itself than the
      treatments that the patients received.

PMID- 21091878
TI  - Vaginal estrogens for the treatment of dyspareunia.
AB  - INTRODUCTION: Vaginal atrophy, which is associated with vaginal itching, burning,
      dryness, irritation, and pain, is estimated to affect up to 40% of postmenopausal
      women. Estrogens play a key role in maintaining vaginal health; women with low
      serum estradiol are more likely to experience vaginal dryness, dyspareunia, and
      reduced sexual activity compared with women who have higher estradiol levels.
      AIMS: The purpose of this review is to assess the prevalence and impact of
      dyspareunia, a symptom of vaginal atrophy, on the health of postmenopausal women
      and to evaluate treatment options using vaginal estrogens (U.S. Food and Drug
      Administration [FDA] approved). METHODS: Relevant published literature was
      identified by searching Index Medicus using the PubMed online database. The
      search terms dyspareunia, vaginal estrogen, vaginal hormone therapy, vaginal
      atrophy, and atrophic vaginitis were the focus of the literature review. RESULTS:
      Current treatment guidelines for vaginal atrophy recommend the use of minimally
      absorbed local vaginal estrogens, along with non-hormonal lubricants or
      moisturizers, coupled with maintenance of sexual activity. Vaginal estrogen
      therapy has been shown to provide improvement in the signs and symptoms of
      vaginal or vulvar atrophy. Vaginal tablets, rings, and creams are indicated for
      the treatment of vaginal atrophy, and the FDA has recently approved a low-dose
      regimen of conjugated estrogens cream to treat moderate-to-severe postmenopausal
      dyspareunia. The use of low-dose vaginal estrogens has been shown to be effective
      in treating symptoms of vaginal atrophy without causing significant proliferation
      of the endometrial lining, and no significant differences have been seen among
      vaginal preparations in terms of endometrial safety. CONCLUSION: Women should be
      informed of the potential benefits and risks of the treatment options available,
      and with the help of their healthcare provider, choose an intervention that is
      most suitable to their individual needs and circumstances.

PMID- 21091879
TI  - Circulating sex hormones play no role in the association between sexual activity
      and the risk of prostate cancer.
AB  - INTRODUCTION: High sexual activity (SA) has been reported to reduce the risk of
      prostate cancer (PC). The role of sex hormones (SHs) in this regard remains
      controversial. AIMS: To determine the impact of SA and SHs on PC development.
      METHODS: In a multicentric hospital-based case-control study, 194 newly diagnosed
      PC patients along with 317 age-matched controls were studied. Sociodemographic
      and medical characteristics of participants were recorded. History of vasectomy
      and sexually transmitted infection (STI), marital status, age at first
      intercourse, premarital sex, and the current frequency of sexual intercourses per
      month (SPM) were evaluated. Total testosterone (TT), free testosterone (FT),
      estradiol (ES), sex hormone binding globulin, and albumin were also measured.
      Logistic regression model was used to identify independent risk factors for PC.
      MAIN OUTCOME MEASURES: (i) The association between SA, SHs, and the risk of PC;
      (ii) The correlation between SHs and SA; (iii) The interaction between SHs and SA
      and established risk factors for PC and erectile dysfunction in determining the
      risk of PC; and (iv) The correlation between SHs and SA in determining the risk
      of PC in different decades of life. RESULTS: Vasectomy, STI, and marital status
      did not differ significantly between two cohorts. Controls reported premarital
      sex more commonly than cases (P < 0.001). Cases had the first intercourse at
      older age (P = 0.03) and had less SPM (P < 0.001). TT, FT, and ES were higher in
      controls (P < 0.001). In multivariate analysis, TT, calculated FT, SPM >4, and
      age at time of marriage <24 were protective against PC. The protective effect of
      high SA and SHs increased as patients' age increased. CONCLUSIONS: High SA as
      well as TT and FT were protective against PC. Their protective role enhances by
      each decade of increasing age. The protective effect of high SA was independent
      from circulating levels of SHs.

PMID- 21091880
TI  - Real-time PCR study of Ang1, Ang2, Tie-2, VEGF, and KDR expression in human
      erectile tissue during aging.
AB  - INTRODUCTION: Aging is a recognized risk factor for erectile dysfunction (ED),
      contributing independently to vascular damage of penile tissue. Vascular
      maintenance depends on angiogenic balance in tissues. Vascular endothelial growth
      factor (VEGF) is a modulator of endothelial cells functions, after engagement to
      specific receptor kinase domain region (KDR). Other factors, such as
      angiopoietins, cross talk with VEGF, modulating its effects. Angiopoietin-1
      (Ang1) and angiopoietin-2 (Ang2) compete for binding to Tie-2 and, while Ang1
      promotes vascular stabilization, Ang2 acts as a partial agonist or antagonist of
      Ang1 signaling, depending on VEGF bioavailability. AIMS: To quantify the
      expression of Ang1, Ang2, Tie-2, VEGF, and KDR by real-time polymerase chain
      reaction (PCR) in human corpus cavernosum (CC) from young and aged healthy
      individuals. METHODS:   Human CC fragments were obtained from organ donors
      without known risk factors to ED and divided in two groups: young (16-35 years)
      and aged (59-74 years). RNA was extracted and converted to cDNA. Real-time PCR
      reactions employed appropriate primers. KDR, Tie-2, Akt, and phospho-Akt protein
      levels were also assessed by Western blotting (WB). Computer-assisted evaluation
      of vascular areas was performed. MAIN OUTCOME MEASURES: Study of angiopoietins
      Tie-2 and VEGF-KDR systems in human CC during aging by real-time PCR and WB. The
      ratios Ang1/Tie-2 and VEGF/KDR and Akt levels were also determined. RESULTS: Real
      time PCR results showed a sixfold significant reduction in the Ang1/Tie-2 ratio
      during aging. Ang2, VEGF, and KDR expression results were highly variable.
      Nevertheless, the ratio VEGF/KDR was significantly higher in the aged
      individuals. Akt and phospho-Akt levels were similar in both groups.
      Immunohistological evaluation revealed a significant decrease in vascular areas
      and endothelial surface in CC with aging, despite no differences found in vessel
      number. CONCLUSIONS: The obtained results suggest an aging-associated
      downregulation of angiopoietins/Tie-2 system and an apparent compensatory
      upregulation of the VEGF/KDR system.

PMID- 21091881
TI  - Intracavernous transplantation of bone marrow-derived mesenchymal stem cells
      restores erectile function of streptozocin-induced diabetic rats.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a frequent complication of diabetes
      mellitus. The efficacy of common ED therapies is low for diabetes-associated ED.
      AIM: To explore the effects of transplantation of bone marrow-derived mesenchymal
      stem cells (BM-MSCs) on improving erectile function of streptozocin (STZ)-induced
      diabetic rats. METHODS: Male Sprague Dawley rats were injected either with STZ to
      induce diabetes or with citrate buffer as controls. Rat BM-MSCs were harvested
      and labeled with CM-DiI (Chloromethylbenzamido derivatives of 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate), and then transplanted into
      corporal cavernosum of STZ-induced diabetic rats. Four weeks after
      transplantation, all rats were analyzed for erectile function and penile
      histology. MAIN OUTCOME MEASURES: Erectile function was evaluated by the ratio
      between intracavernous pressure (ICP) and mean arterial pressure (MAP) during
      electrostimulation of cavernous nerve. Fate of transplanted BM-MSCs was
      identified using immunofluorescence staining. Smooth muscle and endothelium in
      corpora cavernosum were assessed using immunohistochemistry. RESULTS: After BM
      MSCs transplantation, the ICP/MAP ratio was increased significantly compared with
      diabetic controls. Content of smooth muscle and endothelium in corporal cavernosa
      of BM-MSCs transplanted rats was significantly increased compared to diabetic
      controls. Immunofluorescence analysis demonstrated that CM-DiI-labeled BM-MSCs
      could stay in corporal cavernosa for at least 4 weeks and some of them expressed
      von Willebrand Factor, CD31, calponin, or alpha-smooth muscle actin, cells
      markers for endothelial cells or smooth muscle cells, respectively. CONCLUSION:
      Intracavernous transplantation of BM-MSCs had beneficial effects on erectile
      function of diabetic rats and increased the content of endothelium and smooth
      muscle in corporal cavernosum.

PMID- 21091882
TI  - Removal of a long PVC pipe strangulated in the penis by hot-melt method.
AB  - INTRODUCTION: Penile incarceration for erotic or autoerotic purposes has been
      reported in a wide range of age groups, and often presents a significant
      challenge to urologic surgeons. No ready method has been reported for removing a
      polyvinylchloride (PVC) pipe entrapped on the penis. AIM: To present our
      experience in using hot-melt method to remove a constricted PVC pipe on the
      penis. METHODS: A long melting split was made on the PVC pipe entrapped on the
      penis by using the long narrow branch of forceps heated on a gas stove. RESULTS:
      The heated forceps was able to make a melt split on the PVC pipe. Consequently,
      the PVC pipe was removed by pulling the edges of the pipe apart without much
      difficulty. The total operation time was 20 minutes. CONCLUSION: Penile
      incarceration is a urologic emergency, for which resourcefulness is required in
      some unexpected cases. Hot-melting has proved to be an easy and effective method
      for removing penile strangulation by a PVC pipe. To our knowledge, it is the
      first report about the removal of PVC pipe entrapped on a penis.

PMID- 21091883
TI  - Long-term psychological and sexual outcomes of severe penile hypospadias repair.
AB  - INTRODUCTION: Hypospadias is the most common penis malformation, and there exist
      a variety of surgical approaches used to correct the abnormal position of the
      meatus. Although the long-term outcomes of surgery are considered important for
      psychosexual development, only a few attempts have been made to evaluate patient
      satisfaction. AIM: The aim of our study was to evaluate surgical results and
      psychosocial adaptations in a homogeneous group of subjects with severe penile
      hypospadias who underwent the same types of surgical repairs during childhood and
      compare the results to data obtained from age-matched healthy controls. METHODS:
      In this cross-sectional study, 104 men (between 24 and 42 years old) who
      underwent an uncomplicated two-stage hypospadias repair in their childhood and 63
      age-matched healthy men without genital malformations completed the
      questionnaire. MAIN OUTCOME MEASURES:   Difference in self-perception assessed by
      a 15-item questionnaire regarding psychosexual well-being and penile appearance
      between subjects with corrected hypospadias and healthy participants. RESULTS: On
      average, subjects with a hypospadias repair were less satisfied with their
      genital appearance; however, they were more satisfied with their sex lives
      compared to healthy controls. The meatus distance was approximately 1.5 cm from
      the tip of the penis after surgical correction. None of the postoperative
      surgical results correlated with patient satisfaction. Furthermore, the small
      percentage of patients (11%) who were very unsatisfied with their surgical
      outcomes had no significant differences in surgical outcomes compared to
      satisfied patients. However, there was a significant difference between the two
      groups in almost all psychological outcome measures. CONCLUSIONS: In adults who
      underwent an uncomplicated ventral repair of a severe penile hypospadias 20-30
      years earlier, healthy psychosexual development was achieved despite the lack of
      a glanular meatus. Early identification of unsatisfied patients is important for
      appropriate long-term follow-up and counseling.

PMID- 21091884
TI  - Revision of penile prosthesis surgery after use of penile traction therapy to
      increase erect penile length: case report and review of the literature.
AB  - INTRODUCTION: Erectile dysfunction, a common consequence of radical prostatectomy
      (RP), can be managed with placement of a penile prosthesis. Patient satisfaction
      and functional outcomes have been related to penile length after prosthesis
      placement. AIM: We report a case demonstrating the impact of daily penile
      traction therapy in a patient with a previously placed penile prosthesis with the
      goal of enabling revision with a longer device. METHODS: A post-RP patient who
      underwent inflatable penile prosthesis placement 6 years ago complained of
      inability to maintain partner penetration with his device. The patient underwent
      vacuum erection device therapy twice daily for 10 minutes per session for
      approximately 1 year as well as 8 hours of penile traction therapy daily for 8
      months. A revision implant surgery was subsequently attempted. MAIN OUTCOME
      MEASURE: Patient reported functional outcome. RESULTS: Stretched penile length
      increased 2.3 cm after 6 months of traction therapy. A revision surgery enabled
      the placement of a prosthesis that was 20% longer in length (15 cm to 18 cm), and
      erect penile length increased by 4.4 cm. The patient reported that the new
      prosthesis enabled satisfactory maintenance of partner penetration. CONCLUSIONS:
      This case suggests that the use of a penile traction device increases penile
      corporal length, and thus the length of a penile prosthesis that can be implanted
      in a patient with an unsatisfactory prosthesis already in place. Importantly,
      this patient experienced a substantial improvement in erect penile length after
      surgery. It is unknown whether these results are generalizable, either to all
      patients with a previously placed prosthesis or pre-prosthesis patients,
      representing an opportunity for further investigation.

PMID- 21091885
TI  - Are all metabolic syndrome components responsible for penile hemodynamics
      impairment in patients with erectile dysfunction? The role of body fat mass
      assessment.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common disease that is mostly
      vasculogenic in nature. ED correlates with cardiovascular risk factors, with
      endothelial dysfunction being the common link. Hypertension (HTA) and insulin
      resistance are the most important determinants of arteriogenic ED, and are also
      components of the metabolic syndrome (MetS), which supports a strong association
      between MetS and ED. However, MetS and, specifically, obesity interference on
      penile hemodynamics is still controversial. AIM: To evaluate the impact of
      independent MetS criteria and obesity on penile duplex Doppler ultrasound (PDDU)
      parameters in men with ED. METHODS: Consecutive patients (n = 212) referred to a
      unit of PDDU were evaluated for cardiovascular risk factors and MetS (ATP III
      criteria). Body mass index and body fat percentage (BF%) were calculated. Each
      patient underwent a PDDU by the same investigator. Data are expressed as mean +/-
      standard deviation, and statistical significance was considered at P level <
      0.05. Statistical analysis of clinical, laboratory, and PDDU parameters was
      performed with SPSS(r) software. MAIN OUTCOME MEASURES: To evaluate the
      individual power of MetS clusters and obesity as predictive factors for penile
      hemodynamic changes namely mean peak systolic velocity (mPSV). RESULTS: MetS was
      present in 24.8% of men, and 80.8% of them presented penile hemodynamics
      alterations, with mPSV significantly lower comparatively to no MetS patients
      (29.0 vs. 35.4 cm/s, P = 0.004). Multivariate analysis demonstrated that,
      considering all MetS parameters, only HTA was significantly associated with
      diminished mPSV. However, after further adjustment for all cardiovascular risk
      factors, BF% remained the sole independent clinical factor for penile
      hemodynamics impairment. CONCLUSIONS: There is a strong association between MetS
      and ED, but within MetS criteria, only HTA was independently associated with the
      deterioration of penile hemodynamics parameters. Although the classical methods
      of evaluating obesity in MetS were not individually associated with PDDU
      impairment, BF% represented by itself an excellent predictor of vascular ED.

PMID- 21091886
TI  - Linguistic and psychometric validation of the Erection Hardness Score to Spanish.
AB  - INTRODUCTION: The Erection Hardness Score (EHS) is a one-item questionnaire that
      assesses rigidity on a 4-point scale. AIM: To perform a validation of a Spanish
      version of the EHS by comparison with the International Index of Erectile
      Function (IIEF) questionnaire. METHODS: Validation of the EHS included: (i)
      professional translation of the scale; (ii) scientific evaluation of the
      translation from four independent urologists; (iii) assessment on five
      individuals to test correct comprehension and idiomatic adequacy (iv) validation
      of the EHS by a cross-sectional, multicenter comparison with the IIEF. MAIN
      OUTCOME METHODS: Patients were required to respond to a Spanish version of the
      EHS and IIEF. Statistic correlation was carried out between the EHS score and
      IIEF-erectile function domain (EF) score. RESULTS: A total of 125 patients were
      recruited. Overall prevalence of erectile dysfunction (ED) by the EHS
      questionnaire was of 80.2% patients (n=97). Mean EHS was 2.74+/-0.97. Mean IIEF
      EF score was 17.4+/-9.5. The EHS showed good reliability. The rate of missing
      responses to the EHS questionnaire was 0%. A one-factor analysis of variance was
      performed between the EHS and EF subdomain of IIEF (P=0.000). Pearson's
      correlation coefficient between EHS and EF subdomain of IIEF was 0.834, P<0.01.
      CONCLUSIONS: The EHS is a reliable tool to test ED and its Spanish version was
      satisfactorily understood by patients and correlated with IIEF-EF.

PMID- 21091887
TI  - Is metabolic syndrome a useless category in subjects with high cardiovascular
      risk? Results from a cohort study in men with erectile dysfunction.
AB  - INTRODUCTION: Although several studies have demonstrated that MetS is associated
      with a two-fold increase in the risk of cardiovascular (CV) diseases, this risk
      does not appear to be greater than the sum of risks associated with each of its
      individual components. AIM: To determine the association of men with ED and
      individual components of MetS and their subsequent relationship to CV risk, and,
      more specifically whether the sum of the MetS components is greater than the
      individual components in predicting CV risk. METHODS: We longitudinally studied a
      consecutive series of 1,687 (mean age 52.9+/-12.8; range 17-88 years) patients
      attending our clinic for ED and evaluated different clinical and biochemical
      parameters. MAIN OUTCOME MEASURES: Information on major adverse CV event (MACE)
      was obtained through the City of Florence Registry Office. RESULTS: One hundred
      thirty-nine MACE, 15 of which were fatal, occurred during a mean follow-up of
      4.3+/-2.6 years. Subjects with MetS at baseline showed a higher incidence of MACE
      (hazard ratio [HR]=1.77), after adjusting for age, however, the association
      disappeared in an alternative Cox model, adjusting both for age and for
      individual MetS components (HR=1,525 [0,564-4,123]; P=0.408). The two most
      predictive MetS components of CV risk were low high-density lipoprotein (HDL)
      cholesterol and high triglycerides. Exploring possible interactions between
      individual components of MetS and their effect on CV risk using two alternative
      approaches indicates that the effect of MetS components on CV risk is additive,
      but not synergistic. Among subjects with hypertension, after adjusting for age,
      elevated glycemia, and low HDL cholesterol confer relevant additional risk, while
      in subjects with high triglycerides, hyperglycemia increased the risk of incident
      MACE. CONCLUSIONS: With regards to CV risk, the MetS construct seems to add
      little or nothing to the careful assessment of its components. Thus, there is no
      reason to recommend the use of MetS as a diagnostic category in patients with ED.

PMID- 21091888
TI  - Quality assessment tools for observational studies: lack of consensus.

PMID- 21091889
TI  - Oral liquid nutritional supplements for people with dementia in residential aged
      care facilities.
AB  - AIM: This systematic review investigated the prescription, administration and
      effectiveness of oral liquid nutritional supplements (OLNS) for people with
      dementia in residential aged care facilities (RACF). METHODS: A comprehensive
      search of relevant databases, hand searching and cross-referencing found 15
      relevant articles from a total of 2910 possible results. Articles which met the
      inclusion criteria were critically appraised by two independent reviewers using
      the relevant Joanna Briggs Institute (JBI) appraisal checklist. Data were
      extracted using the relevant JBI extraction instruments. No data synthesis was
      possible due to clinical and methodological heterogeneity. RESULTS: Included
      studies examined a range of strategies, issues and results related to OLNS for
      persons with dementia in RACFs; however there appear to be significant gaps in
      the current body of research, particularly in relation to examinations of
      effectiveness. CONCLUSIONS: This review was unable to produce a definitive
      finding regarding effectiveness. OLNS may improve the nutritional state of
      residents with dementia and help prevent weight loss, and there is some
      suggestion that it may slow the rate of cognitive decline. However, in order for
      OLNS to be effective, nursing and care staff need to ensure that sufficient
      attention is paid to the issues of prescription and administration.

PMID- 21091890
TI  - Thickened fluids for people with dementia in residential aged care facilities.
AB  - AIM: This systematic review aimed to establish best practice in relation to
      thickened fluids for people with dementia living in residential aged care
      facilities. METHODS: This review considered all types of studies that examined
      the prescription and administration of thickened fluids to people with dementia
      in residential aged care facilities. English-language articles published from
      1995 to 2008 were sought in a comprehensive search of an extensive range of
      databases, online sources and unpublished literature. Two independent reviewers
      critically appraised each article using the relevant Joanna Briggs Institute
      System for the Unified Management, Assessment and Review of Information (JBI
      SUMARI) instruments, then data were extracted from those articles that met the
      inclusion criteria. No meta-analysis was possible because of significant clinical
      and methodological heterogeneity, therefore results are reported narratively.
      RESULTS: From 112 papers originally identified, 14 met the inclusion criteria and
      formed the basis of the findings. Nine studies recommend the use of thickened
      fluids as a strategy to maintain adequate fluid intake for persons with dementia
      with dysphagia in residential aged care and four papers recommend their use for
      people with dementia in general. One paper reported that the use of thickened
      fluids was found to be acceptable to older people in the event of dementia and
      dysphagia. CONCLUSIONS: From the retrieved data, evidence-based best practices
      cannot be concluded. It can, however, be cautiously inferred that thickened
      fluids may be effective for residents with dementia if set guidelines are
      instituted.

PMID- 21091891
TI  - Effectiveness of voice rehabilitation on vocalisation in postlaryngectomy
      patients: a systematic review.
AB  - BACKGROUND: Laryngeal cancer is one of the most common malignant neoplasia of the
      head and neck. Its incidence has been increasing steadily all over the world.
      Many patients will undergo total laryngectomy with or without radical neck
      dissection after being diagnosed. After this surgery, normal speech is lost, and
      a permanent stoma in the middle of the neck is left. Therefore, voice
      rehabilitation is one of the most difficult challenges that these patients must
      overcome. In order to support the patients, otolaryngologists, nursing
      specialists and speech pathologists have explored several different methods for
      voice rehabilitation. Variations exist on the approaches of rehabilitation and
      indicators selected to measure the effectiveness. There is a need to undertake a
      systematic review to provide a plan of care and ascertain the effectiveness
      regarding different voice rehabilitation programs for postlaryngectomy patients.
      REVIEW OBJECTIVE: To critically analyse the literature and present the best
      available evidence related to the effectiveness of voice rehabilitation program
      on postlaryngectomy patients. SEARCH STRATEGY: A three-step search strategy was
      utilised. An initial limited search of MEDLINE and CINAHL databases was
      undertaken followed by an analysis of the text words contained in the title and
      abstract to identify the optimal index terms. A second extensive search using all
      identified key words and index terms was then undertaken. Third, the reference
      list and bibliographies of all identified reports and articles were searched for
      additional studies. The measurement index included voice intelligibility, volume,
      clarity, quality of voice, patients' satisfaction, quality of life, etc. The
      search included reports in English and Chinese. SELECTION CRITERIA: The review
      considered any randomised controlled trials that addressed voice rehabilitation
      methods in postlaryngectomy patients. In the absence of randomised controlled
      trials, other quantitative research designs, such as non-randomised controlled
      trials, cohort studies and case-controlled studies, were considered for
      inclusion. DATA COLLECTION AND ANALYSIS: Full copies of articles considered to
      meet the inclusion criteria were obtained for critical appraisal by two reviewers
      using the CASP (Critical Appraisal Skills Program) and McMaster scales. We
      utilised the 60% fulfilling of the evaluation scale items as the cut-off point
      and articles with a quality score less than 60% were excluded. Details of
      eligible trials were extracted and summarised by two reviewers independently
      using standardised data extraction tools developed by the Joanna Briggs
      Institute. RESULTS: Twenty-two articles were included in the review (Appendix I).
      Different voice rehabilitation methods for laryngectomees were investigated in
      the included studies including oesophageal voice, electrolarynx voice and
      surgical voice restoration. One cohort studies, five prospective studies, five
      retrospective studies and 11 descriptive studies were included. Because of the
      heterogeneity of included studies, meta-analysis was not possible. Therefore, the
      results were presented in narrative summary. The following main findings were
      identified: 1 At present, oesophageal speech, electrolarynx and tracheoesophageal
      were the commonly used voice rehabilitation methods with total laryngectomy
      patients. 2 Among these three methods, the success rate of electrolarynx and
      tracheoesophageal is much higher than oesophageal speech. 3 The intelligibility
      and speech quality of electrolarynx was lower than tracheoesophageal. 4 Patient
      satisfaction and self-assessed quality of life was better in tracheoesophageal
      group. 5 The objective index was similar between excellent tracheoesophageal and
      oesophageal speech patients. Conclusion  1 Electrolarynx is the easiest vocal
      rehabilitation method for total laryngectomy patients to use as it requires
      little training and does not limit the patients. But patients' satisfaction was
      lower because of the mechanical voice and noise. 2 Oesophageal speech is the
      hardest vocal rehabilitation method to learn. It needs a long period of time to
      practise and requires the patient to be in good physical condition and to be
      relatively young. The success rate was relatively lower; however, it is the most
      commonly used rehabilitation method in developing countries because of low cost.
      3 Tracheoesophageal is the most commonly used voice rehabilitation method in
      developed countries. It is a surgical method that could be performed as either a
      primary procedure or secondary procedure. Reported patient quality of life and
      satisfaction following tracheoesophageal were the best; however, there are
      complications and the frequent replacement of the prostheses is an important
      problem yet to be solved. Implication for practice  1 Voice rehabilitation after
      total laryngectomy is an immediate and long-term problem that patients and health
      worker must face. 2 Healthcare workers should understand the advantages and
      disadvantages of each voice rehabilitation method in detail to assist people with
      total laryngectomy to make the most appropriate decision in regard to
      rehabilitation method taking into consideration their age, sex, physical
      condition, job, economic status and other context factors. Implication for
      research  1 Further high-quality studies comparing the effectiveness of
      oesophageal speech, electrolarynx and tracheoesophageal vocal rehabilitation
      methods are needed, especially with the subjective and objective outcome index
      concurrently. 2 Further investigation is required to identify strategies to
      decrease the complications of tracheoesophageal and reduce frequency of required
      tracheoesophageal replacement. 3 More research is needed in the context of
      developing countries where healthcare resources may be limited.

PMID- 21091892
TI  - Impact of patient characteristics on orthopaedic and trauma patients' perceptions
      of individualised nursing care.
AB  - RATIONALE AND OBJECTIVES: Relatively few studies have investigated the
      relationship between patient characteristics and individualised care, in relation
      to the improvement of care efficiency, efficacy and quality. Individualised care
      is a key concept in health strategy and policy in Western countries. The aim of
      this exploratory study was to identify orthopaedic and trauma patients'
      characteristics relating to their perceptions of individualised nursing care in
      Western hospital settings. METHODS: A cross-sectional questionnaire survey was
      conducted among orthopaedic and trauma patients (n=1126) from acute care in
      hospitals from five countries: Finland, Greece, Sweden, the UK and the USA, in
      2005-06. The data were analysed using descriptive statistics, one-way analysis of
      variance and a multivariate analysis of variance (manova) of the main effects.
      RESULTS: The separate examination of each background factor showed statistically
      significant differences between patients' perceptions of individualised care. In
      the multivariate analysis the statistically significant main effects, associated
      with patients' perceptions, were age, gender, education and type of admission.
      These explained 13% of the variance in the support of patient individuality in
      care and 19% in perceived individuality in care received. CONCLUSIONS: These
      results can be used in individualising care to different patient groups and in
      prioritising and focusing quality programs to improve care. Detailed questions
      about specific aspects of patients' experiences are likely to be more useful in
      monitoring hospital performance from the patients' perspective.

PMID- 21091893
TI  - Evaluation of an intensive desensitisation, oral tolerance therapy and hunger
      provocation program for children who have had prolonged periods of tube feeds.
AB  - BACKGROUND: Some children with feeding difficulties may require nasogastric tube
      feeding or insertion of a percutaneous endoscopic gastrostomy (PEG) from a young
      age. A small cohort of these children can develop severe oral aversions that can
      delay the re-introduction of oral feeding. Multidisciplinary approaches that
      provide an intensive approach are deemed the most effective method of
      intervention to reduce nasogastric and PEG dependency. METHODS: Two children and
      their parents received an intensive approach to reduce PEG feeds (Child A and
      Child B), while one child and her parents elected to receive a traditional
      feeding clinic approach (Child C). The mean age of the participants was 4 years 4
      months. RESULTS: Child A initially took 2090 kJ (44% daily nutritional
      requirement) via her PEG before the intensive program, and Child B took 100%
      daily nutritional requirement via his PEG. Three months post the intervention,
      Child A took 100% of her nutritional requirements orally and Child B had reduced
      PEG requirement significantly to 38% of daily nutritional requirement. Child C
      showed no changes in PEG versus oral intake. Children who received the
      intervention were able to remain focused on mealtimes for longer, with fewer
      instances of leaving the table. Parents altered their language styles post
      coaching on the intensive intervention using fewer reprimands. No changes with
      these behaviours were noted with Child C. CONCLUSIONS: Although this was a small
      pilot study, there are some strategies used within an intensive multidisciplinary
      context that can enable children to reduce their reliance on PEG feeds
      significantly.

PMID- 21091894
TI  - Advances in endoscopic diagnosis and treatment of Barrett's esophagus.
AB  - Barrett's esophagus (BE) is defined as abnormal specialized columnar metaplasia
      with intestinalization in place of the normal squamous esophageal epithelium.
      Gastroesophageal reflux disease is a known risk factor for BE; nonetheless BE is
      also detected in asymptomatic individuals. Other risk factors for BE include
      smoking, male gender, age over 50 and obesity. Patients diagnosed with BE
      (without dysplasia) are recommended to undergo endoscopic surveillance every 3-5
      years. Advances in imaging techniques (such as narrow band imaging,
      autofluorescence imaging and confocal laser endomicroscopy) have the potential to
      improve the detection of dysplasia and early cancer, thus making surveillance a
      more cost-effective endeavor. Patients with high grade dysplasia (HGD) and early
      cancer have a high rate of progression to invasive adenocarcinoma and
      traditionally these patients were treated with esophagectomy. The rapid
      advancement of endoscopic therapeutic techniques along with a low risk of
      complications have made endoscopic therapy an acceptable alternative to an
      esophagectomy in patients with HGD and early cancer. Several endoscopic treatment
      techniques such as endoscopic mucosal resection, multipolar electrocoagulation,
      photodynamic therapy, argon plasma coagulation, cryotherapy, and radiofrequency
      ablation have been studied for endoscopic treatment.

PMID- 21091895
TI  - Controversy of proton pump inhibitor and clopidogrel interaction: a review.
AB  - A proton pump inhibitor (PPI) is often co-prescribed with clopidogrel to reduce
      the gastrointestinal risk of bleeding ulcers in patients following acute coronary
      syndrome or a stent implant. However, the safety issue of such practice has been
      scrutinized after some studies reporting an increased incidence of cardiovascular
      events and mortality, although there have also been contrary research reports.
      This has lead to a warning statement from the US Food and Drug Administration
      cautioning the concomitant use of PPI and clopidogrel. This review examines the
      evidence of PPI as gastroprotective agent, histamine H(2) antagonists as an
      alternative therapy, the influence of PPI on the antiplatelet effect of
      clopidogrel, and the controversies of various studies.

PMID- 21091896
TI  - XRCC1 downregulated through promoter hypermethylation is involved in human
      gastric carcinogenesis.
AB  - OBJECTIVE: To analyze the expression and aberrant methylation of X-ray repair
      cross-complementing gene 1 (XRCC1) in gastric carcinogenesis, and identify the
      molecular mechanism of gastric carcinogenesis. METHODS: The method based on
      methyl binding domain protein (MBD) immuno-precipitation and promoter microarray
      was employed to screen the gastric cancer-related methylation-sensitive gene. An
      immunohistochemistry assay was applied to detect the protein expression of XRCC1
      in the multistep progression of gastric carcinogenesis. The mRNA expression of
      XRCC1 was determined by real-time PCR in tumor tissues and their corresponding
      non-tumorous tissues. The methylation status and Arg194Trp and Arg399Gln
      polymorphisms of XRCC1 in gastric cancer and gastritis tissues were analyzed by
      methylation-specific PCR, bisulfite genomic sequencing and direct DNA sequencing,
      respectively. RESULTS: Promoter microarray screening and identification suggested
      that XRCC1 was a methylation-sensitive gene. Immunochemistry results showed that
      XRCC1 protein expression gradually decreased with progression of gastric mucosal
      lesions (P < 0.05). The positive rate of XRCC1 in patients with well/moderately
      differentiated gastric cancer was significantly higher than patients with poorly
      differentiated gastric cancer (P < 0.05). The mRNA expression of XRCC1 in gastric
      cancer tissues was significantly lower than that in the non-tumorous tissues (P <
      0.05). Meanwhile, XRCC1 methylation in gastric cancer tissues was more frequent
      than that in the gastritis tissues (P < 0.05), and the downregulation of XRCC1
      expression was relevant to methylation (P < 0.05). CONCLUSION: The expression of
      XRCC1 is downregulated in gastric carcinogenesis, and promoter hypermethylation
      may be one of the mechanisms contributing to its downregulation.

PMID- 21091897
TI  - Model for end-stage liver disease combined with serum prealbumin to predict the
      prognosis of patients with decompensated liver cirrhosis.
AB  - OBJECTIVE: To evaluate the prognostic value of model for end-stage liver disease
      (MELD) combined with serum prealbumin (PA) in patients with decompensated liver
      cirrhosis. METHODS: A total of 252 patients were enrolled in the study and
      followed 1 year. PA was measured and MELD score was calculated on the first day
      of admission. Analysis of variance (anova) was used to assess correlation between
      PA level and MELD score. Multivariable Cox proportional hazards model was used to
      screen the prognosis related factors. Kaplan-Meier survival curves were drawn.
      RESULTS: Of the 252 patients, 28 died within 3 months, 58 within 6 months and 91
      within 1 year. Serum PA level in dead patients was significantly lower than that
      in survival patients (P < 0.005) and decreasing with increasing of MELD score.
      Cox analysis showed that MELD score > 18 (RR = 2.749) and PA < 70 mg/L (RR =
      2.412) were independent prognosis risk factors. The risk ratio of MELD score
      combined with PA level (1.854, P < 0.01) was higher than that of MELD score alone
      (1.054, P < 0.05). Kaplan-Meier survival curve analysis showed that MELD score <=
      18 combined with PA >= 70 mg/L could clearly discriminate patients who would
      survive or die within 6 month and 1 year follow up. CONCLUSION: MELD score <= 18
      combined with PA >= 70 mg/L could predict the 6-month and 1-year prognosis of
      patients with decompensated liver cirrhosis, and was superior to that of MELD
      score alone.

PMID- 21091898
TI  - Evaluating human liver reserve function by measuring serum concentrations of
      phenacetin and its metabolites.
AB  - OBJECTIVES: To evaluate human liver reserve function (LRF) by a simple and
      efficient method for measuring serum concentrations of phenacetin and its
      metabolites. METHODS: Overall 20 patients with liver cirrhosis (Child-Pugh score
      >= 7, aged 48-79 years), 30 healthy young volunteers (aged 18-40 years), and 20
      healthy elderly volunteers (aged 61-80 years) were enrolled. All participants
      received a single oral dose of 0.5 g phenacetin. Liquid chromatography tandem
      mass spectrometry was used to determine the serum concentrations of phenacetin
      and its metabolites, including acetaminophen, acetaminophen glucuronide and
      acetaminophen sulfate. RESULTS: The serum concentration of phenacetin was
      significantly higher in cirrhotic patients than those in either of the healthy
      volunteer groups (P < 0.001). It was higher in healthy elderly volunteers than
      that in healthy young ones but there was no statistically significant difference
      (P > 0.05) between them. The serum concentrations of acetaminophen, acetaminophen
      glucuronide and acetaminophen sulfate were significantly lower in cirrhotic
      patients than in the healthy controls (P < 0.001). The serum concentrations of
      these three metabolites in healthy elderly volunteers were lower than those in
      healthy younger volunteers but again, there was no statistical significant
      difference (P > 0.05). The serum concentration of acetaminophen in healthy male
      volunteers was significantly higher than that in the women (P < 0.05).
      CONCLUSION: Monitoring cytochrome P450 1A2 (CYP450 1A2)-mediated phenacetin
      metabolism is a simple and efficient method for evaluating human LRF. This method
      would warrant further validation in a large cohort clinical study.

PMID- 21091899
TI  - Transparent cap improves patients' tolerance of colonoscopy and shortens
      examination time by inexperienced endoscopists.
AB  - OBJECTIVE: Up to 10% of colonoscopy procedures cannot be completed and polyps may
      be missed because of patients' discomfort and the endoscopists' technique. The
      aim of this study was to test the feasibility and safety of attaching a
      transparent cap to improve the outcome, especially for inexperienced
      endoscopists. METHODS: A total of 250 patients were randomized to undergoing
      either a cap-fitted colonoscopy (CCF) or a normal colonoscopy without a cap
      (NCCF). The procedures were performed by an experienced or inexperienced
      endoscopist, and the time to reach the cecum, the total colonoscopy time and the
      polyp detection rate were recorded. Visual analogue scales (VAS) assessing the
      severity of abdominal pain and distension were obtained. RESULTS: For the
      experienced endoscopist there was no difference between CCF and NCCF on the time
      to reach the cecum and the time for the whole procedure. But for the
      inexperienced endoscopist, both times were significantly shorter in the CCF group
      than in the NCCF group (9.48 min vs. 12.45 min; 18.50 min vs. 21.89 min,
      respectively, P < 0.05). No complication was observed except some abdominal pain
      and distension. The VAS scores of abdominal pain and distension were
      significantly lower in CCF group than those in the NCCF group for the two
      endoscopists. There was no significant difference in the number of polyps found
      between the two groups. CONCLUSION: A cap-fitted colonoscopy can shorten the
      examination time for inexperienced endoscopists. It can also reduce the patients'
      discomfort during the procedure.

PMID- 21091900
TI  - Effect of cytotoxic T lymphocyte-associated molecule 4 1661 gene polymorphism on
      its expression and transcription in ulcerative colitis.
AB  - OBJECTIVE: Our aim was to investigate the expression of cytotoxic T lymphocyte
      associated molecule 4 (CTLA-4) in ulcerative colitis (UC) and to evaluate the
      effect of CTLA-4 gene -1661A/G polymorphism on CTLA-4 expression and
      transcription. METHODS: A total of 20 UC patients and 22 healthy controls matched
      by age and sex were enrolled at Zhongnan Hospital of Wuhan University in central
      China. The CTLA-4 -1661A/G polymorphism was genotyped by the polymerase chain
      reaction-restriction fragment length polymorphism method. A Western blot analysis
      was performed to determine the full length CTLA-4 (flCTLA-4) protein expression
      in the peripheral blood of the UC patients. Serum-soluble CTLA-4 (sCTLA-4) levels
      were measured by enzyme-linked immunosorbent assay. CTLA-4-1661G mutant promoter
      transcription function was analyzed by site-directed PCR-based mutagenesis.
      RESULTS: CTLA-4 protein expression on CD4(+) T cells in UC patients was lower
      than that in the healthy controls (P < 0.001) while serum sCTLA-4 in the UC
      patients was significantly higher than that in the healthy controls (P < 0.001).
      No correlation was found between flCTLA-4 and sCTLA-4 expression levels and the 
      1661 A/G polymorphism of the CTLA-4 gene. Meanwhile, CTLA-4 -1661 allele A had no
      significant impact on the promoter activity compared with allele G (P > 0.05).
      CONCLUSION: CTLA-4 expressions were aberrant in UC patients compared with the
      healthy controls. CTLA-4 -1661A/G polymorphism had no significant impact on CTLA
      4 expression and transcription in the peripheral CD4 T cells of UC patients.

PMID- 21091901
TI  - Efficient differentiation of newly derived human embryonic stem cells from
      discarded blastocysts into hepatocyte-like cells.
AB  - OBJECTIVE: To establish an optimal method to isolate and culture human embryonic
      stem (hES) cells from discarded blastocysts and to differentiate these cells into
      hepatocyte-like cells. METHODS: Discarded human blastocysts of days 5-6 were
      cultured on mouse embryonic fibroblast cell feeder layers. Cells from the inner
      cell mass were isolated and subsequently cultured in vitro. To induce the
      formation of embryoid bodies (EB), dissociated ES cells were cultured in hanging
      drops for 5 days. The resulting EB were plated onto 100 mm plastic gelatin-coated
      dishes and allowed to attach for the outgrowth culture in the presence of
      hepatocyte growth factor for an additional 15 days. RESULTS: The hES cells had
      typical morphological characteristics: round or elliptic nest-like colonies with
      distinct cell borders and a smooth surface, significant swelling growth, compact
      cell aggregation, and relatively big nucleus compared to a small cytoplasm. The
      hES cells were identified by positive alkaline phosphatase staining. All had
      normal karyotypes and expressed octamer-binding transcription factor and cell
      surface markers, including stage-specific embryonic antigens SSEA-3, SSEA-4, and
      tumor rejection antigens TRA-1-60 and TRA-1-81. The cells could be differentiated
      to form teratomas in vivo. The hES cells could be induced to differentiate into
      hepatocyte-like cells and 70-80% of the cells expressed liver-associated
      proteins. CONCLUSION: Three hES cell lines have been successfully isolated and
      cultured from discarded human blastocysts. The hES cells can be efficiently
      differentiated into hepatocyte-like cells using the EB system. These cells
      possess the potential for treatment of liver diseases.

PMID- 21091902
TI  - Unusual endoscopic retrograde cholangiopancreaticography complication in a
      patient with Mirrizi's syndrome.

PMID- 21091903
TI  - Assessment of farm-level biosecurity measures after an outbreak of avian
      influenza in the United Kingdom.
AB  - During Avian Influenza outbreaks in England, the 'AI Order' states that a poultry
      keeper may be required to keep domestic birds separate from wild birds. This
      study aimed to assess a) how effectively this was done and b) the negative impact
      this had for bird owners and animal welfare during the November 2007 Highly
      Pathogenic Avian Influenza (HPAI) outbreak in Suffolk, UK. A voluntary
      questionnaire was posted to holdings (n=296) that were within 10 km of an
      infected premises; these holdings were required to separate domestic and wild
      birds where possible. Holdings were identified during outbreak investigations
      conducted by the authorities. Holdings of all sizes were included. A sample of
      holdings received a follow-up visit or telephone call to validate the
      questionnaire (n=29). From the 38% of eligible holdings that responded, 13% (95%
      CI 7-22%) left their birds outdoors throughout the outbreak. If game birds were
      excluded, 9% (CI 4-17%) of holdings did not house their birds. Major cost and
      welfare problems were rare; however, there were exceptions. Enforced housing was
      often relaxed before a minor welfare problem deteriorated. Contact between wild
      and domestic birds was greatly reduced during the outbreak, resulting in a
      reduced probability of HPAI transmission via wild birds for most, but not all,
      holdings.

PMID- 21091904
TI  - Engineering skeletal muscle tissue--new perspectives in vitro and in vivo.
AB  - Muscle tissue engineering (TE) has not yet been clinically applied because of
      several problems. However, the field of skeletal muscle TE has been developing
      tremendously and new approaches and techniques have emerged. This review will
      highlight recent developments in the field of nanotechnology, especially
      electrospun nanofibre matrices, as well as potential cell sources for muscle TE.
      Important developments in cardiac muscle TE and clinical studies on Duchenne
      muscular dystrophy (DMD) will be included to show their implications on skeletal
      muscle TE.

PMID- 21091905
TI  - Novel X-linked inhibitor of apoptosis inhibiting compound as sensitizer for TRAIL
      mediated apoptosis in chronic lymphocytic leukaemia with poor prognosis.
AB  - Given that aggressive DNA damaging chemotherapy shows suboptimal efficacy in
      chronic lymphocytic leukaemia (CLL), alternative therapeutic approaches are
      needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is able
      to induce tumour-specific apoptosis. However, apoptosis might be inhibited by
      elevated levels of X-linked inhibitor of apoptosis (XIAP). Use of XIAP-inhibiting
      compounds might sensitize primary CLL cells towards TRAIL-mediated apoptosis. A
      novel small molecule, compound A (CA), an inhibitor of XIAP, was used in
      combination with TRAIL to induce apoptosis in primary CLL cells (n = 48). XIAP
      was significantly more highly expressed in primary CLL cells (n = 28) compared to
      healthy B cells (n = 16) (P = 0.02). Our data obtained by specific knock-down of
      XIAP by siRNA identified XIAP as the key factor conferring resistance to TRAIL in
      CLL. Combined treatment with CA/TRAIL significantly increased apoptosis compared
      to untreated (P = 8.5 * 10-10), solely CA (P = 4.1 * 10-12) or TRAIL treated (P =
      4.8 * 10-10) CLL cells. CA rendered 40 of 48 (83.3%) primary CLL samples
      susceptible to TRAIL-mediated apoptosis. In particular, cells derived from
      patients with poor prognosis CLL (ZAP-70(+) , IGHV unmutated, 17p-) were highly
      responsive to this drug combination. Our highly-effective XIAP inhibitor CA, in
      concert with TRAIL, shows potential for the treatment of CLL cases with poor
      prognosis and therefore warrants further clinical investigation.

PMID- 21091906
TI  - Transgenic modelling of cytokine polarization in the lung.
AB  - The lung is one of the commonest sites of exposure to environmental allergen or
      pathogen, so the expression of a variety of cytokines in the lung is dynamically
      regulated by inflammatory or structural cells in the lung. In the last decades,
      characterization of the local lung cytokine milieu in allergic or injury models
      has identified a collective role of certain cytokines, such as type 1 or type 2
      cytokines, driving polarized inflammatory and tissue phenotypes. With the
      development of transgenic mouse modelling systems, the effector function of
      individual cytokine and the pathophysiological consequences of cytokine
      polarization in the lung have been effectively evaluated. Here, we present an
      overview of the transgenic systems currently used to assess the biological
      function of cytokine or other mediators in the lung. We discuss the inflammatory
      and tissue phenotypes detected in the lungs of transgenic mice over-expressing
      representative T helper type 1 (interferon-gamma, interleukin-12), T helper type
      2 (interleukins -4, -5, -9, -10 and -13), and T helper type 17 cytokines. The
      effects of genetic modification of cytokine receptors or transcriptional factors
      such as GATA-3 and T-bet in pulmonary inflammation and remodelling tissue
      responses are also discussed because these transcription factors are regarded as
      essential regulators of cytokine polarization. Finally, we discuss the
      limitations and future application of transgenic approaches in the studies of
      human lung diseases characterized by cytokine polarization.

PMID- 21091907
TI  - Mannose-binding lectin deficiency influences innate and antigen-presenting
      functions of blood myeloid dendritic cells.
AB  - Mannose-binding lectin (MBL) is a serum lectin that plays a significant role in
      innate host defence. Individuals with mutations in exon 1 of the MBL2 gene have
      reduced MBL ligand binding and complement activation function and increased
      incidence of infection. We proposed that, during infection, MBL deficiency may
      impact on dendritic cell (DC) function. We analysed the blood myeloid DC (MDC)
      surface phenotype, inflammatory cytokine production and antigen-presenting
      capacity in MBL-deficient (MBL-D) individuals and MBL-sufficient (MBL-S)
      individuals using whole blood culture supplemented with zymosan (Zy) or MBL
      opsonized zymosan (MBL-Zy) as a model of infection. Zy-stimulated MDCs from MBL-D
      individuals had significantly increased production of interleukin (IL)-6 and
      tumour necrosis factor (TNF)-alpha. Stimulation with MBL-Zy significantly
      decreased IL-6 production by MDCs from MBL-D, but had no effect on TNF-alpha
      production. MDCs from both MBL-S and MBL-D individuals up-regulated expression of
      the activation molecule CD83, and down-regulated expression of homing (CXCR4),
      adhesion (CD62L, CD49d) and costimulatory (CD40, CD86) molecules in response to
      Zy and MBL-Zy. MDC from both MBL-D and MBL-S individuals induced proliferation of
      allogeneic (allo) T cells following Zy or MBL-Zy stimulation; however, MBL-D
      individuals demonstrated a reduced capacity to induce effector allo-T cells.
      These data indicate that MBL deficiency is associated with unique functional
      characteristics of pathogen-stimulated blood MDCs manifested by increased
      production of IL-6, combined with a poor capacity to induce effector allo-T-cell
      responses. In MBL-D individuals, these functional features of blood MDCs may
      influence their ability to mount an immune response.

PMID- 21091908
TI  - Identification of a novel immunomodulatory gliadin peptide that causes
      interleukin-8 release in a chemokine receptor CXCR3-dependent manner only in
      patients with coeliac disease.
AB  - The autoimmune enteropathy, coeliac disease (CD), is triggered by ingestion of
      gluten-containing grains. We recently reported that the chemokine receptor CXCR3
      serves as a receptor for specific gliadin peptides that cause zonulin release and
      subsequent increase in intestinal permeability. To explore the role of CXCR3 in
      the immune response to gliadin, peripheral blood mononuclear cells from both
      patients with CD and healthy controls were incubated with either pepsin-trypsin
      digested gliadin or 11 alpha-gliadin synthetic peptides in the presence or
      absence of a blocking anti-CXCR3 monoclonal antibody. Supernatants were analysed
      for interleukin-6 (IL-6), IL-8, IL-10, IL-13, IP-10 (CXCL10), tumour necrosis
      factor-alpha and interferon-gamma. Gliadin broadly induced cytokine production
      irrespective of the clinical condition. However, IL-8 production occurred only in
      a subgroup of individuals and cells of the phagocytic lineage were the main
      source. Induction of IL-8 was reproduced by one of a comprehensive panel of
      synthetic alpha-gliadin peptides and was abrogated when CXCR3 was blocked before
      stimulation with either gliadin or this peptide in the CD group but not in the
      control group, suggesting that gliadin-induced IL-8 production was CXCR3
      dependent gliadin induced IL-8 production only in CD.

PMID- 21091909
TI  - Oestrogen-mediated protection of experimental autoimmune encephalomyelitis in the
      absence of Foxp3+ regulatory T cells implicates compensatory pathways including
      regulatory B cells.
AB  - Oestrogen (17beta-oestradiol, E2) is a highly effective treatment for
      experimental autoimmune encephalomyelitis (EAE) that may potentiate Foxp3+
      regulatory T (Treg) cells, which in turn limit the expansion of encephalitogenic
      T-cell specificities. To determine if Treg cells constitute the major non
      redundant protective pathway for E2, we evaluated E2 protection of EAE after
      targeted deletion of Foxp3 expression in Foxp3-DTR mice. Unexpectedly, E2-treated
      Foxp3-deficient mice were completely protected against clinical and histological
      myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-induced EAE before
      succumbing to diphtheria toxin-induced mortality. This finding indicated the
      presence of alternative E2-dependent EAE-protective pathways that could
      compensate for the lack of Treg cells. Further investigation revealed that E2
      treatment inhibited proliferation and expression of CCL2 and CXCL2, but enhanced
      secretion of interleukin-10 (IL-10) and IL-13 by MOG-35-55-specific spleen cells.
      These changes occurred concomitantly with increased expression of several
      chemokines and receptors, including CXCL13 and CXCR5, and the negative co
      activation molecules, PD-L1 and B7.2, by B cells and dendritic cells.
      Furthermore, E2 treatment resulted in higher percentages of spleen and lymph node
      T cells expressing IL-17, interferon-gamma and tumour necrosis factor-alpha, but
      with lower expression of CCR6, suggesting sequestration of MOG-35-55 peptide
      specific T cells in peripheral immune organs. Taken together, these data suggest
      that E2-induced mechanisms that provide protection against EAE in the absence of
      Foxp3+ Treg cells include induction of regulatory B cells and peripheral
      sequestration of encephalitogenic T cells.

PMID- 21091912
TI  - Research priorities of adult intensive care nurses in 20 European countries: a
      Delphi study.
AB  - AIMS: This paper is a report of a three round Delphi study of intensive care
      nursing research priorities in Europe (October 2006-April 2009). BACKGROUND:
      Internationally, priorities for research in intensive care nursing have received
      some attention focusing on healthcare interventions and patient needs. Studies as
      early as the 1980s identified priorities in the United States, United Kingdom,
      Hong Kong and Australia. Research priorities of intensive care nurses across the
      European Union are unknown. METHODS: The participants, invited in 2006, included
      110 intensive care nurses, managers, educators and researchers from 20 European
      Critical Care Nursing Associations. Delphi round one was an emailed questionnaire
      inviting participants to list important areas for research. The list was content
      analysed and developed into an online questionnaire for rounds two and three. In
      round two, participants ranked the topics on a scale of 1-6 (not important to
      extremely important). Mean scores of round two were added to the questionnaire of
      round three and participants ranked the topics again. RESULTS: There were 52
      research topics in 12 domains. There was a dominance of priorities in five main
      areas: patient safety; impact of evidence based practice on outcomes; impact of
      workforce on outcomes; wellbeing of patients and relatives; and impact of end-of
      life care on staff and practice. CONCLUSIONS: The results reflect worldwide
      healthcare concerns and objectives and highlight topics that nurses view as
      fundamental to the care of critically ill patients. These topics provide a
      platform for future research efforts to improve clinical practice and care of
      patients in intensive care.

PMID- 21091910
TI  - Interplay of transcription factors in T-cell differentiation and function: the
      role of Runx.
AB  - Over the past years, increasing numbers of distinct subsets have been discovered
      and identified for a T lymphocytes' entity. Differentiation and function of each
      T cell subset are controlled by a specific master transcription factor.
      Importantly, Runt-related transcription factors, particularly Runx1 and Runx3,
      interplay with these master regulators in various aspects of T cells' immunity.
      In this review article, we first explain roles of Th-Pok and Runx3 in
      differentiation of CD4 versus CD8 single positive cells, and later focus on cross
      regulation of Th-Pok and Runx3 and their relationship with other factors such as
      TCR strength. Next, we provide evidences for the direct interplay of Runx1/3 with
      T-bet and GATA3 during Th1 versus Th2 commitment to activate or silence
      transcription of signature cytokine genes, IFNgamma and IL4. Lastly, we explain
      feed-forward relationship between Runx1 and Foxp3 and discuss roles of Runx1 in
      regulatory T cells' suppressive activity. This review highlights an essential
      importance of Runx molecules in controlling various T cell subsets'
      differentiation and functions through molecular interplay with the master
      transcription factors in terms of protein-protein interaction as well as
      regulation of gene expression.

PMID- 21091911
TI  - PD-1 negatively regulates interleukin-12 expression by limiting STAT-1
      phosphorylation in monocytes/macrophages during chronic hepatitis C virus
      infection.
AB  - Hepatitis C virus (HCV) is remarkably efficient at evading host immunity to
      establish chronic infection. During chronic HCV infection, interleukin-12 (IL-12)
      produced by monocytes/macrophages (M/Mphi) is significantly suppressed.
      Programmed death-1 (PD-1), an inhibitory receptor on immune cells, plays a
      pivotal role in suppressing T-cell responses during chronic viral infection. To
      determine whether PD-1 regulates IL-12 production by M/Mphi during chronic HCV
      infection, we examined the expressions of PD-1, its ligand PDL-1, and their
      relationship with IL-12 production in M/Mphi from HCV-infected, HCV-resolved, and
      healthy subjects by flow cytometry. Toll-like receptor (TLR) -mediated IL-12
      production by M/Mphi was selectively suppressed, while PD-1/PDL-1 expressions
      were up-regulated, in HCV-infected subjects compared with HCV-resolved or healthy
      subjects. Up-regulation of PD-1 was inversely associated with the degree of IL-12
      inhibition in HCV infection. Interestingly, the reduced response of M/Mphi from
      HCV-infected individuals to TLR ligands appeared not to be the result of a lack
      of the ability to sense pathogen, but to an impaired activation of intracellular
      janus kinase/signal transducer and activator of transfection (STAT) pathway as
      represented by inhibited STAT-1 phosphorylation in M/Mphi from HCV-infected
      individuals compared with HCV-negative subjects. Successful HCV treatment with
      pegylated interferon/ribavirin or blocking PD-1/PDL-1 engagement ex vivo led to
      reduced PD-1 expression and improved IL-12 production as well as STAT-1
      activation in M/Mphi from HCV-infected individuals. These results suggest that
      the PD-1 inhibitory pathway may negatively regulate IL-12 expression by limiting
      STAT-1 phosphorylation in M/Mphi during chronic HCV infection.

PMID- 21091913
TI  - Communication between children and health professionals in a child hospital
      setting: a Child Transitional Communication Model.
AB  - AIM: This paper is a report of a further analysis of data from an ethnographic
      study of the nature of communication between children and health professionals in
      a child hospital setting. BACKGROUND: There is a paucity of research on the
      nature of communication between health professionals and child patients.
      Additionally, theory has not been developed to any great extent in the
      communication literature on children. METHOD: Using an ethnographic approach,
      fieldwork took place in one specialized children's hospital during 2005. Forty
      nine children, aged 6-16 years, with a variety of medical and surgical
      conditions, participated. Data were collected through semi-participant
      observations, unstructured interviews, participatory activities and documentary
      evidence. FINDINGS: Health professionals positioned children as either passive
      bystanders or active participants in the communication process. These two
      positions, passive bystander and active participant, signified the extent of
      children's inclusion or exclusion in the communication process and the degree to
      which children's communication needs were met or not. A Child Transitional
      Communication Model presented in this paper draws on multiple theoretical
      perspectives to explain why health professionals placed children as either a
      passive bystander or an active participant in the communication process.
      CONCLUSION: Children prefer to oscillate between a passive bystander and active
      participant position within the communication process, depending on their needs
      at any given point in time. This challenges the insistence for stronger child
      participation in all matters that affect them, in isolation of debates
      surrounding children's need for support/protection and any potential negative
      consequences of children's active participation.

PMID- 21091914
TI  - Do specific dietary constituents and supplements affect mental energy? Review of
      the evidence.
AB  - The numbers of marketing claims and food, beverage, and drug products claiming to
      increase mental energy have risen rapidly, thus increasing the need for
      scientific specificity in marketing and food label claims. Mental energy is a
      three-dimensional construct consisting of mood (transient feelings about the
      presence of fatigue or energy), motivation (determination and enthusiasm), and
      cognition (sustained attention and vigilance). The present review focuses on four
      dietary constituents/supplements (Ginkgo biloba, ginseng, glucose, and omega-3
      polyunsaturated fatty acids) to illustrate the current state of the literature on
      dietary constituents and mental energy. The strongest evidence suggests effects
      of Ginkgo biloba on certain aspects of mood and on attention in healthy subjects,
      as well as associations between omega-3 polyunsaturated fatty acids and reduced
      risk of age-related cognitive decline. Limitations of the current data and
      challenges for future research are discussed.

PMID- 21091916
TI  - Curcumin and obesity: evidence and mechanisms.
AB  - The incidence of obesity is increasing worldwide and is hence considered a major
      public health concern. Obesity underlies the development of several metabolic
      complications including cardiovascular diseases, diabetes, and inflammation.
      Research on ways to slow the development of obesity have traditionally focused on
      dietary and lifestyle modifications such as restricting caloric intake and
      increasing physical activity. An area that has recently aroused considerable
      research interest is investigating the potential role of spices, particularly the
      Asian spice turmeric, for combating obesity. Curcumin is the active ingredient in
      turmeric. Evidence suggests curcumin may regulate lipid metabolism, which plays a
      central role in the development of obesity and its complications. The present
      review addresses the evidence and mechanisms by which curcumin may play a role in
      downregulating obesity and reducing the impact of associated problems.

PMID- 21091915
TI  - Can consuming flavonoids restore old microglia to their youthful state?
AB  - Microglial cells, which are resident macrophages in the central nervous system,
      are "primed" in the aged brain and are hypersensitive to messages emerging from
      immune-to-brain signaling pathways. Thus, in elderly individuals who have an
      infection, microglia overreact to signals from the peripheral immune system and
      produce excessive levels of cytokines, causing behavioral pathology including
      serious deficits in cognition. Importantly, recent studies indicate dietary
      flavonoids have anti-inflammatory properties and are capable of mitigating
      microglial cells in the brains of aged mice. Thus, dietary or supplemental
      flavonoids and other bioactive agents have the potential to restore the
      population of microglial cells in the elderly brain to its youthful state. This
      review briefly describes the immune-to-brain signaling pathways, consequences of
      microglial cell priming, and the potential of flavonoids to mitigate brain
      microglia and cognitive deficits induced by inflammatory cytokines.

PMID- 21091917
TI  - Micronutrient adequacy and morbidity: paucity of information in children with
      cerebral palsy.
AB  - A literature review was conducted to investigate the status of vitamins and
      minerals in children with cerebral palsy and the implications of various
      deficiencies on health outcomes. Children with cerebral palsy commonly have
      feeding difficulties, which significantly impact their growth, general health,
      and life expectancy. Current nutritional literature focuses on energy
      expenditure, with little information available on other parameters, such as
      micronutrient status. Due to the paucity of micronutrient research in these
      children, the impacts of deficiencies and benefits in other populations have been
      considered. The role of micronutrients in maintaining cellular homeostasis
      throughout all body systems highlights a need for future research and monitoring
      of their levels, particularly in vulnerable populations with well-documented
      incidence of undernutrition.

PMID- 21091918
TI  - Qualitative research in nutrition and dietetics: data collection issues.
AB  - The wide scope of qualitative enquiry presents the researcher with a number of
      choices regarding data collection and sampling. Selecting data collection and
      sampling techniques can therefore be somewhat daunting, particularly because,
      often, there is no single, universally accepted 'correct' option. Appropriate
      research methods are, however, crucial to ensure high-quality research. This
      review, the second in the series, provides an overview of the principal
      techniques of data collection and sampling that may be used for qualitative
      research in nutrition and dietetics. In addition, it describes a process for
      choosing appropriate data collection and sampling methods that considers the
      extent to which they provide data that answers the research question(s) and are
      compatible with the philosophical assumptions about ontology, epistemology and
      methodology that underpin the overall design of a study. Finally, it discusses
      the central role that the researcher plays in qualitative data collection and
      encourages researchers to acknowledge and reflect upon their impact on the data.
      Other reviews in this series provide a model for embarking on a qualitative
      research project in nutrition and dietetics, an overview of the principal
      techniques of data analysis and quality assessment of this kind of research, and
      some practical advice relevant to nutrition and dietetics, along with glossaries
      of key terms.

PMID- 21091919
TI  - Hydration status of nursing home residents in Taiwan: a cross-sectional study.
AB  - AIM: To investigate fluid intake, dehydration and the key factors affecting
      nursing home residents' fluid intake and dehydration. BACKGROUND: Inadequate
      fluid intake is a common problem in nursing homes, but related studies on risk
      factors of inadequate fluid intake and dehydration in nursing homes have seldom
      been explored in detail in nursing research. METHODS: A cross-sectional design
      was developed and implemented. The sample was composed of 111 residents from
      nursing homes in Kaohsiung, Taiwan. Data of demographic characteristics,
      activities of daily living, and modes of feeding were collected and tested for
      association with hydration status. Laboratory data on hydration status were also
      collected. Data was collected from October to December 2005. RESULTS: Average
      daily fluid intake of the residents was 2083 mL. Forty-five per cent of the
      residents had a daily fluid intake that was less than their estimated
      requirements. Seventeen per cent of the residents had a blood urea
      nitrogen/creatinine ratio that was higher than 20. Mode of feeding and a
      diagnosis of dementia were the significant predictors of daily fluid intake and
      contributed to 28.8% of the total variance in daily fluid intake. Age, gender and
      a diagnosis of heart disease were the significant predictors of blood urea
      nitrogen/creatinine ratio, contributing to 17.0% of the total variance in the
      ratio. CONCLUSION: The nursing home residents in our study, especially females or
      those fed orally, had a comparatively higher prevalence of inadequate fluid
      intake. It is important to assess periodically the hydration status of nursing
      home residents and adjust their fluid intake accordingly.

PMID- 21091920
TI  - Qualitative research in nutrition and dietetics: data analysis issues.
AB  - Although much of the analysis conducted in qualitative research falls within the
      broad church of thematic analysis, the wide scope of qualitative enquiry presents
      the researcher with a number of choices regarding data analysis techniques. This
      review, the third in the series, provides an overview of a number of techniques
      and practical steps that can be taken to provide some structure and focus to the
      intellectual work of thematic analysis in nutrition and dietetics. Because
      appropriate research methods are crucial to ensure high-quality research, it also
      describes a process for choosing appropriate analytical methods that considers
      the extent to which they help answer the research question(s) and are compatible
      with the philosophical assumptions about ontology, epistemology and methodology
      that underpin the overall design of a study. Other reviews in this series provide
      a model for embarking on a qualitative research project in nutrition and
      dietetics, an overview of the principal techniques of data collection, sampling
      and quality assessment of this kind of research and some practical advice
      relevant to nutrition and dietetics, along with glossaries of key terms.

PMID- 21091921
TI  - Qualitative research in nutrition and dietetics: assessing quality.
AB  - In recent years, qualitative research has become much more widely used in
      healthcare settings and undoubtedly has much to offer nutrition and dietetics.
      Its value is, however, still sometimes called into question and, for those
      unfamiliar with qualitative approaches, it can be difficult to grasp what
      distinguishes 'good' qualitative research from that which has been less
      rigorously conceived and conducted. This review, the fourth in the series, aims
      to highlight some of the key scientific debates around the quality criteria that
      can be applied to qualitative research, and offers some flexible guidelines that
      may be used both in producing and assessing qualitative health research,
      including studies in nutrition and dietetics. Other reviews in this series
      provide a model for embarking on a qualitative research project in nutrition and
      dietetics, an overview of the principal techniques of data collection, sampling
      and analysis and some practical advice relevant to nutrition and dietetics, along
      with glossaries of key terms.

PMID- 21091922
TI  - Outcomes of overseas kidney transplantation in chronic haemodialysis patients in
      Taiwan.
AB  - AIM: Overseas kidney transplantation has often been reported to have
      unsatisfactory outcomes. This study aims to compare post-transplantation outcomes
      between overseas and domestic kidney transplant (KT) recipients in Taiwan.
      METHODS: The Taiwanese National Health Insurance Research Database was used to
      identify 310 domestic and 643 overseas KT recipients, who survived for longer
      than 1 month after the transplantation, in a cohort of 45,453 chronic
      haemodialysis patients in 1997-2002. Cox proportional hazards models were used to
      assess risks of mortality and graft failure. RESULTS: The 1, 3 and 5 year
      survival rates for domestic KT recipients were 96.5%, 93.3% and 91.6%,
      respectively, while those for overseas KT recipients were 94.9%, 87.9% and 77.1%,
      respectively (P = 0.015). For the overseas group, those who received a KT before
      2001 had significantly higher hazard ratios of mortality and graft failure (2.85
      and 1.71, respectively). However, for those receiving a KT in 2001-2002, no
      significant outcome difference could be found between overseas and domestic
      recipients. CONCLUSION: The risk disparity between overseas and domestic KT
      recipients is mainly attributable to when the transplantation was performed. In
      attempting to dissuade potential recipients from organ trafficking, merely
      emphasizing the previously acknowledged poor outcomes no longer suffices as a
      valid reason.

PMID- 21091923
TI  - Treatment of nephrotic idiopathic membranous nephropathy with monthly i.v. pulse
      cyclophosphamide and oral steroids: a single centre's retrospective study.
AB  - AIM: While the best treatment of nephrosis-inducing idiopathic membranous
      nephropathy (IMN) is controversial, some trials have suggested positive outcomes
      following treatment with oral cyclophosphamide used in combination with steroids.
      However, data on i.v. cyclophosphamide plus steroids in treatment of nephrotic
      IMN are few. METHODS: The charts of every patient diagnosed with membranous
      nephropathy in the Renal Division of Renji Hospital, Shanghai Jiao Tong
      University School of Medicine, Shanghai, from January 2003 to December 2009 (n =
      189) were retrospectively analyzed. Patients with nephrotic IMN (n = 32) were
      treated with monthly i.v. cyclophosphamide (500-750 mg/m(2)) and oral prednisone
      for at least 6 months. Efficacy as well as safety and tolerability of this
      regimen were evaluated. RESULT: Thirty-two patients with nephrotic IMN (56% male,
      age 51.5 +/- 12.6 years, estimated glomerular filtration rate 73.7 +/- 20.0
      mL/min per 1.73 m(2)) were included in our study. During the median follow-up
      duration of 30.0 (12.5-42.8) months, 40.6% of patients achieved complete
      remission, while 40.6% achieved partial remission. Relapse occurred in five
      patients in a median of 16 (11.5-26) months after cessation of immunosuppressive
      treatment. No patients developed renal insufficiency during the follow up, while
      16 side-effects were noted in 10 patients. Complete remission rates at 3, 6 and
      15 months were 0%, 12.5% and 40.6% and remission rates were 21.9%, 68.8% and
      81.2%, respectively. Complement 3 deposition was significantly associated with
      the probability of non-remission. CONCLUSION: Monthly i.v. pulse cyclophosphamide
      plus oral steroids may be an alternative treatment option in Chinese patients
      with nephrotic IMN.

PMID- 21091924
TI  - How to design a randomized controlled trial.
AB  - Randomized controlled trials are the ideal study design to evaluate the
      effectiveness of health-care interventions. The conduct of a clinical trial is a
      collaborative effort between participants, investigators and a range of health
      care professionals involved both centrally and locally in the coordination and
      execution of the trial. In this article, the key steps that are required to
      design a randomized controlled trial are summarized.

PMID- 21091926
TI  - Alternatives to routine ultrasound for eligibility assessment prior to early
      termination of pregnancy with mifepristone-misoprostol.
AB  - OBJECTIVE: To test the feasibility and efficacy of an approach that foregoes the
      routine use of ultrasound for the determination of eligibility for medical
      termination of pregnancy. DESIGN: Prospective trial. SETTING: Ten termination of
      pregnancy clinics in the USA. POPULATION: A total of 4484 women seeking
      termination of pregnancy with mifepristone-misoprostol. METHODS: Women provided
      estimates of the date of their last menstrual period and underwent pelvic
      bimanual and ultrasound examinations. We compared estimates of gestational age
      using these three methods. MAIN OUTCOME MEASURE: Proportion of women of <=9
      weeks' gestation by woman or provider estimate, but >9 weeks' gestation by
      ultrasound. RESULTS: The reliance on women's report of their last menstrual
      period together with physical examination to determine their eligibility for
      termination of pregnancy with mifepristone-misoprostol would result in few women
      (63/4008 or 1.6%) accepted for treatment outside the current limits of standard
      mifepristone-misoprostol regimens used for early termination of pregnancy (i.e.
      <=63 days' gestation on ultrasound). CONCLUSIONS: Last menstrual period and
      physical examination alone, without the routine use of ultrasound, are highly
      effective for the determination of women's eligibility for early termination of
      pregnancy with mifepristone-misoprostol.

PMID- 21091927
TI  - Mycoplasmas in pregnancy.
AB  - The genital mycoplasmas have been implicated in a number of adverse outcomes of
      pregnancy. Spontaneous preterm labour and preterm birth is an important
      contributor to perinatal mortality and morbidity. If Mycoplasma hominis plays an
      integral part in this problem, it is likely to contribute through its involvement
      with bacterial vaginosis. Ureaplasmas induce cytokines and inflammation, making a
      casual association compelling. The role of Mycoplasma genitalium and Mycoplasma
      fermentans is less clear, but M. genitalium is potentially pathogenic and should
      be treated if detected. There is considerable evidence for the role of M. hominis
      in post-partum and post-abortal sepsis, and for ureaplasmas causing chronic lung
      disease or death in very low birthweight infants. The role of the genital
      mycoplasmas in adverse outcomes of pregnancy is complicated by the presence or
      absence of bacterial vaginosis, and this association requires further research.

PMID- 21091925
TI  - Lipid signalling in pathogenic fungi.
AB  - In recent years, the study of lipid signalling networks has significantly
      increased. Although best studied in mammalian cells, lipid signalling is now
      appreciated also in microbial cells, particularly in yeasts and moulds. For
      instance, microbial sphingolipids and their metabolizing enzymes play a key role
      in the regulation of fungal pathogenicity, especially in Cryptococcus neoformans,
      through the modulation of different microbial pathways and virulence factors.
      Another example is the quorum sensing molecule (QSM) farnesol. In fact, this QSM
      is involved not only in mycelial growth and biofilm formation of Candida
      albicans, but also in many stress related responses. In moulds, such as
      Aspergillus fumigatus, QSM and sphingolipids are important for maintaining cell
      wall integrity and virulence. Finally, fungal cells make oxylipins to increase
      their virulence attributes and to counteract the host immune defences. In this
      review, we discuss these aspects in details.

PMID- 21091928
TI  - Upregulated mRNA expression of major histocompatibility complex class I chain
      related gene A in colon and activated natural killer cells of Chinese patients
      with ulcerative colitis.
AB  - OBJECTIVE: To explore the expression of major histocompatibility complex class I
      chain-related gene A (MICA) and its ligand in colonic mucosa and the role of MICA
      natural killer (NK) group 2D (NKG2D) interaction in activating NK cells in
      ulcerative colitis (UC) patients. METHODS: Intestinal mucosal biopsies were
      obtained from patients with UC and the controls. The expression of major
      histocompatibility complex class I-related gene (MIC) genes was determined by a
      reverse transcription polymerase chain reaction (RT-PCR) and the imaging of MICA
      expressed on colonic mucosa was measured by confocal microscopy resonance
      scanning. NKG2D and intracellular interferon (IFN)-gamma expressions on NK cells
      were assayed by flow cytometry. RESULTS: The relative amount of MICA mRNA in the
      colonic mucosa of UC patients was significantly higher than in that of the
      controls (3.5408 +/- 2.6658 vs 1.0477 +/- 0.7201, P = 0.001), as were the major
      histocompatibility complex class I chain-related gene B (MICB) (8.9879 +/- 3.2893
      vs 4.6293 +/- 1.2616, P < 0.001) and NKG2D mRNA expression (2.4395 +/- 0.8147 vs
      1.1624 +/- 0.3954, P < 0.001). Confocal microscopy resonance scanning had shown
      that MICA was localized predominantly on the basolateral membranes of the
      epithelium. Further flow cytometry confirmed that the percentage of IFN-gamma
      producer NK cells that expressed NKG2D in peripheral blood lymphocytes was higher
      in UC patients than in the healthy controls (45.36% +/- 12.47% vs 27.45% +/-
      9.30%, P < 0.001). CONCLUSION: MICA, MICB and NKG2D were upregulated in the
      colonic mucosa of UC and were associated with activating NK cells with promoted
      NKG2D and IFN-gamma production.

PMID- 21091929
TI  - Editorial: Fatty liver disease: a growing public health problem worldwide.

PMID- 21091931
TI  - Epidemiology of the metabolic syndrome in the USA.
AB  - The metabolic syndrome is a common complex entity that has emerged as a worldwide
      epidemic and major public health care concern with a prevalence of approximately
      25% in the United States. There have been a number of different definitions of
      the metabolic syndrome but all center around the metabolic abnormalities of
      central obesity, hypertension, decreased high-density lipoproteins and elevated
      triglycerides with insulin resistance as the uniting physiologic factor. The
      importance of the metabolic syndrome is not just related to its high prevalence
      rate but also because it predicts the development of diabetes and cardiovascular
      disease. Nonalcoholic fatty liver disease is now recognized to be the hepatic
      component of the metabolic syndrome, which along with its individual components -
      particularly diabetes and elevated triglycerides, are the major risk factors for
      the development of nonalcoholic steatohepatitis (NASH); the most severe form of
      nonalcoholic fatty liver disease. NASH may progress to cirrhosis, hepatocellular
      carcinoma, and liver failure. It is currently the third most common cause for
      liver transplantation and is projected to be the leading cause for liver
      transplantation in 2020. Weight loss (via diet or bariatric surgery) and vitamin
      E have recently been demonstrated to be effective treatments of NASH. Although
      these and other agents may prove to be effective treatments for NASH, the most
      effective therapeutic strategy would be early screening and intervention to
      prevent the development of insulin resistance and oxidative stress at a societal
      level.

PMID- 21091932
TI  - Diagnosis and management of alcoholic liver disease.
AB  - Alcohol is the most commonly used hepatotoxin worldwide. About 90% of heavy
      drinkers (more than 60 g/day of alcohol) show evidence of fatty livers, while
      only 10-35% develop alcoholic hepatitis and 5-15% developed cirrhosis. The daily
      intake of alcohol that results in liver injury varies and depends on a number of
      risk factors. Alcoholic disease developes at lower doses in females, Hispanic,
      obese objects, and patients with hepatitis C. Insights into the pathogenesis of
      alcohol-induced liver injury has improved significantly but the translation into
      clinical benefit has been slow. The importance of continued abstinence and
      correction of nutritional deficiencies are major components in the long-term
      management of liver disease. Alcohol hepatitis has a variable mortality and the
      prognosis is determined most commonly by the modified discriminant function. The
      mocel of end-stage liver disease (MELD) is being increasingly used to predict
      outcome in alcoholic hepatitis even though standard cut offs are not available.
      Anti-inflammatory therapy with corticosteroids and anticytokine therapy with
      corticosteroids and pentoxifylline are effective for patients with severe
      alcoholic hepatitis. Patients with endstage liver disease should be considered
      for liver transplantation. Six months of abstinence is considered to be a
      requirement prior to transplant, but this length of time may be adjusted in
      individual bases.

PMID- 21091930
TI  - Pathogenesis of alcoholic liver disease: interactions between parenchymal and non
      parenchymal cells.
AB  - The development of alcoholic liver disease (ALD) is a complex process involving
      both the parenchymal and non-parenchymal cells in the liver. The impact of
      ethanol on hepatocytes can be characterized as a condition of organelle stress
      with multifactorial changes in hepatocellular function accumulating during
      ethanol exposure. These changes include oxidative stress, mitochondrial
      dysfunction, decreased methylation capacity, endoplasmic reticulum stress,
      impaired vesicular trafficking and altered proteasome function. Injury to
      hepatocytes is attributed, in part, to ethanol metabolism by the hepatocytes.
      Changes in the structural integrity of hepatic sinusoidal endothelial cells, as
      well as enhanced inflammation in the liver during ethanol exposure are also
      important contributors to injury. Activation of hepatic stellate cells initiates
      the deposition of extracellular matrix proteins characteristic of fibrosis.
      Kupffer cells, the resident macrophages in the liver, are particularly critical
      to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes
      Kupffer cells to activation by lipopolysaccharides via toll-like receptor 4. This
      sensitization enhances the production of inflammatory mediators, such as tumor
      necrosis factor-alpha and reactive oxygen species that contribute to hepatocyte
      dysfunction, necrosis and apoptosis of hepatocytes and the generation of
      extracellular matrix proteins leading to fibrosis. In this review we provide an
      overview of the complex interactions between parenchymal and non-parenchymal
      cells in the liver during the progression of ethanol-induced liver injury.

PMID- 21091933
TI  - Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic
      steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease
      in the USA and many other parts of the world. Its prevalence continues to rise;
      currently affecting about one in four adults and 10% of children in the USA.
      NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in
      general follows a benign, no-progressive clinical course, to nonalcoholic
      steatohepatitis (NASH), a more serious form of NAFLD that may progress to
      cirrhosis and end-stage liver disease. Currently, the diagnosis of NASH requires
      an invasive liver biopsy with drawbacks of sampling and interpretation error.
      Clinical risk factors for NASH include diabetes and the metabolic syndrome;
      however, these are not sufficiently predictive of the condition by themselves.
      Routine liver enzyme levels are not reliable; however, novel plasma hepatocyte
      cell death markers either alone or in combination with clinical risk factors are
      potential non-invasive diagnostic tools for the future. This review provides a
      concise overview of the role non-invasive diagnostic tools for the
      differentiation of fatty liver from NASH as well as for the determination of
      presence and extent of fibrosis.

PMID- 21091934
TI  - Histopathological evaluation of fatty and alcoholic liver diseases.
AB  - Fatty liver disease (FLD) represents a common form of hepatic dysfunction among
      adults and children. Recognition of steatosis is usually straightforward but the
      differential diagnosis is broad. Macrovesicular steatosis may occur due to
      alcohol use or metabolic factors including obesity and hyperinsulinemia.
      Steatosis is, in some patients, accompanied by varying degrees of inflammation,
      ballooning hepatocyte degeneration or fibrosis, or both. The pathologist's
      recognition and interpretation of these features, when present, is critical for
      the classification and prognostication of the disease. Recent advances in the
      study of FLD have yielded new information for the surgical pathologist to guide
      the interpretation of steatosis in children and adults, and in patients with
      other forms of liver disease such as chronic viral hepatitis. This article
      details the current terminology for various forms of FLD, highlights the key
      histological features and reviews recent advances in the field.

PMID- 21091935
TI  - Portal hypertension: diagnosis and management with particular reference to
      variceal hemorrhage.
AB  - Portal hypertension is a cause a major luminal gut hemorrhage, most often from
      esophageal varices. Identification of those with varices, and administration of
      therapies to reduce the likelihood of initial bleeding improve patient outcomes.
      Beta blocker therapy or variceal band ligation are most often used in this
      context. Management of acute variceal hemorrhage (including routine use of
      antibiotics) is followed by initiating strategies to reduce the frequency of
      recurrent bleeding. Mortality from portal hypertensive bleeding has been
      diminished by use of these interventions.

PMID- 21091936
TI  - Gastrointestinal surgery in patients with liver failure.
AB  - There is an increased risk of morbidity and mortality after nonhepatic surgery in
      patients with liver failure compared to patients without liver failure. Mortality
      was shown to be higher after emergent surgery than after elective surgery in
      patients with cirrhosis. In patients with liver failure who undergo nonhepatic
      surgery, preoperative assessment is vital in order to reduce the high risk of
      postoperative complications and mortality.

PMID- 21091937
TI  - Liver transplantation for fatty liver disease.

PMID- 21091938
TI  - Contraction of occult choroidal neovascular membrane and rupture of the retinal
      pigment following verteporfin and bevacizumab treatment.

PMID- 21091939
TI  - Wernicke's encephalopathy because of pancreatitis in a young boy.

PMID- 21091940
TI  - Peripapillary sclera thickness in human eyes with glaucoma.

PMID- 21091941
TI  - Clearance of dying ARPE-19 cells by professional and nonprofessional phagocytes
      in vitro- implications for age-related macular degeneration (AMD).
AB  - PURPOSE: Failure of retinal pigment epithelial (RPE) cells and macrophages to
      engulf different dying cells in the retina may result in accumulation of debris
      and development of age-related macular degeneration (AMD). The dynamics and
      influence of different treatments on this clearance process can be studied in
      vitro using human ARPE-19 cells and macrophages as phagocytes modelling dry and
      wet type of AMD, respectively. METHODS: Death through extracellular matrix
      detachment using polyHEMA-coated surfaces (anoikis) and UV irradiation
      (apoptosis) was induced in ARPE-19 cells. Two-coloured phagocytic assays were
      performed to quantify the amount of dying cells phagocytes engulfed (flow
      cytometry) and for visualization (fluorescent and scanning electron microscopy).
      The effect of phosphatidylserine inhibition with recombinant annexin-V and
      glucocorticoid (triamcinolone) treatment on the phagocytic process was tested.
      RESULTS: The clearance of anoikic and apoptotic cells by nondying ARPE-19 cells
      over 8 hr of co-incubation increased over time (at 8 hr, over 53% and 35% of the
      phagocytes contained engulfed dying cells, respectively). The human macrophages
      engulfed the anoikic and apoptotic ARPE-19 cells with seven and four times lower
      capacity, respectively. Phosphatidylserine appearance on the dying cells did not
      affect, but triamcinolone treatment enhanced the phagocytosis of the dying cells
      by macrophages. CONCLUSIONS: ARPE-19 cells are more efficient in clearing anoikic
      than UV-induced apoptotic cells. Macrophages are less efficient in the clearance
      process than ARPE-19 cells. The present model can be used for studying both dry
      and wet type of AMD in vitro and for testing different pharmacological aspects
      affecting this disease.

PMID- 21091942
TI  - Peroxisome proliferator-activated receptor activators protect sebocytes from
      apoptosis: a new treatment modality for acne?
AB  - BACKGROUND: The main function of the human sebaceous gland is sebum excretion.
      Increased sebum levels combined with follicular hyperkeratinization are a
      prerequisite of acne vulgaris. As peroxisome proliferator-activated receptors
      (PPARs) are known to control lipid metabolism in several human tissues they have
      been considered to be involved in the pathogenesis of acne vulgaris. OBJECTIVES:
      To investigate the effect of activators of PPAR-alpha (WY14643), PPAR-gamma
      (rosiglitazone) and PPAR-delta (L-165.041) on basal and staurosporine-induced
      apoptosis in the human sebocyte cell line SZ95 in vitro. METHODS: After defining
      the basal effects of PPAR activators on membrane integrity (lactate dehydrogenase
      release) and DNA synthesis (5-bromodeoxyuridine incorporation), apoptosis was
      determined by the release of histone-associated DNA fragments. The underlying
      signalling events were detected by Western blotting and the use of specific
      inhibitors against p44/42 and protein kinase B (PKB)/Akt. RESULTS: PPAR
      activators of all three subsets offer antiapoptotic effects, with L-165.041 being
      the most potent. This compound induced the activation of PKB/Akt and p44/42, two
      kinases involved in antiapoptosis and proliferation, respectively. An inhibition
      of these kinases by specific inhibitors reversed the suppression of histone
      associated DNA fragments by L-165.041, indicating that these signalling pathways
      participate in the observed antiapoptotic effect. CONCLUSIONS: The present data
      suggest that activators of PPAR, in particular of the delta subset, might have
      beneficial effects on acne vulgaris by inhibiting the release of lipids in the
      context of sebocyte apoptosis.

PMID- 21091944
TI  - B vitamins and the aging brain.
AB  - Deficiencies of the vitamins folate, B(12) , and B(6) are associated with
      neurological and psychological dysfunction and with congenital defects. In the
      elderly, cognitive impairment and incident dementia may be related to the high
      prevalence of inadequate B vitamin status and to elevations of plasma
      homocysteine. Plausible mechanisms include homocysteine neurotoxicity,
      vasotoxicity, and impaired S-adenosylmethionine-dependent methylation reactions
      vital to central nervous system function. In light of this, it is imperative to
      find safe ways of improving vitamin B status in the elderly without exposing some
      individuals to undue risk.

PMID- 21091943
TI  - Dietary fatty acids and the aging brain.
AB  - Aging contributes to physiological decline and vulnerability to disease. In the
      brain, even with minimal neuronal loss, aging increases oxidative damage,
      inflammation, demyelination, impaired processing, and metabolic deficits,
      particularly during pathological brain aging. In this review, the possible role
      of docosahexaenoic acid (DHA) in the prevention of age-related disruption of
      brain function is discussed. High-fat diabetogenic diets, cholesterol, and the
      omega-6 fatty acid arachidonate and its prostaglandin metabolites have all been
      implicated in promoting the pathogenesis of Alzheimer's disease. Evidence
      presented here shows DHA acts to oppose this, exerting a plethora of pleiotropic
      activities to protect against the pathogenesis of Alzheimer's disease.

PMID- 21091945
TI  - Brain aging: lessons from community studies.
AB  - Dementia is an acquired highly disabling syndrome common among elderly people.
      Alzheimer's disease is the most frequent type of dementia, and its prevalence is
      rapidly increasing due to the aging of populations. Therefore, the need to find
      effective preventive means is pressing. Population studies allow identification
      of risk/protective factors for dementia/Alzheimer's disease, thus leading to
      preventive strategies that can be implemented in the general population to reduce
      the incidence of this disorder. Presented here is an overview of the main
      findings of epidemiological studies on nutritional factors and nutrition-related
      pathological conditions, as related to dementia and Alzheimer's disease.

PMID- 21091946
TI  - Translating research on brain aging into public health: a new type of
      immunotherapy for Alzheimer's disease.
AB  - The identification of disease-causing mutations in Alzheimer's disease has
      contributed greatly to the understanding of the pathogenesis of this disease. The
      amyloid-beta (Abeta) peptide has come into focus and is believed to be central to
      the pathogenesis of Alzheimer's disease. With only symptomatic treatment
      available, efforts to develop new therapeutics aimed at lowering the amount of
      Abeta peptides in the affected brain have intensified. In particular,
      immunotherapy against Abeta peptides has attracted considerable interest, as it
      offers the possibility to generate highly specific molecules targeting highly
      specific moieties. Due to intense research efforts and massive investments at
      universities and in the pharmaceutical industry, the outlook for patients and
      their relatives has never been brighter.

PMID- 21091947
TI  - 23rd Marabou Symposium: Nutrition and the Aging Brain.

PMID- 21091948
TI  - 23rd Marabou Symposium: Nutrition and the Aging Brain.

PMID- 21091949
TI  - How hardwired is the brain? Technological advances provide new insight into brain
      malleability and neurotransmission.
AB  - Any discussion of the impact of nutrition and environment on the brain is based
      on the premise that the brain is malleable, but just how malleable is this most
      complex of all organs? And to what extent does the term "malleability" extend
      beyond subtle functional changes into the realms of morphology and connectivity?
      Recent methodological advances have provided new insight into these issues and
      have revealed synapse populations that turn over at high rates and synaptic
      receptors that are continuously on the move. The unveiling of this unsuspected
      structural plasticity has prompted new research on a class of enzymes (matrix
      metalloproteinases) that regulate the physical constraints imposed by
      extracellular matrix molecules. The realization that the brain is more
      "softwired" than previously anticipated emphasizes the relevance of current
      endeavors to explore the impact of nutrition and exercise on brain function and
      structure.

PMID- 21091950
TI  - Global aging and the brain.
AB  - Intrinsic aging of the brain and its relationship to age-related
      neurodegenerative diseases need to be understood as part of global aging, which
      results from gradual accumulation of a variety of kinds of cellular and molecular
      damage. While certain kinds of molecular lesions are particularly associated with
      specific diseases, there is substantial overlap between the pathways causing
      disease and those contributing to global aging. Growing evidence indicates that
      the global aging process is more malleable than used to be thought. This needs to
      be taken into account in efforts to improve health and retention of mental
      capital across the life course.

PMID- 21091951
TI  - Functional expressions of the aging brain.
AB  - In the conventional view, aging of the brain is associated with atrophy vascular
      abnormalities and loss of volume in hippocampus and amygdala. Cognitively, aging
      is associated with slowing of processing and memory loss. However, many studies
      of aging do not examine the cases to exclude demented people. The nutrition and
      memory in the homebound elderly study (NAME) excluded cases clinically diagnosed
      as having dementia. Cortical atrophy based on MRI ratings was significantly
      correlated with vascular disease, white matter hyperintensities, processing
      speed, and memory but not hippocampus and amygdala volume. Renal function and
      homocysteine were also associated with cortical atrophy but not with the
      cognitive variables. In conclusion, brain atrophy of aging in the absence of
      dementia is related to vascular disease but not hippocampal atrophy. Studies of
      nutritional interventions should consider using MRI atrophy rather than cognition
      as outcome.

PMID- 21091952
TI  - Vascular basis for brain degeneration: faltering controls and risk factors for
      dementia.
AB  - The integrity of the vascular system is essential for the efficient functioning
      of the brain. Aging-related structural and functional disturbances in the macro-
      or microcirculation of the brain make it vulnerable to cognitive dysfunction,
      leading to brain degeneration and dementing illness. Several faltering controls,
      including impairment in autoregulation, neurovascular coupling, blood-brain
      barrier leakage, decreased cerebrospinal fluid, and reduced vascular tone, appear
      to be responsible for varying degrees of neurodegeneration in old age. There is
      ample evidence to indicate vascular risk factors are also linked to
      neurodegenerative processes preceding cognitive decline and dementia. The
      strongest risk factor for brain degeneration, whether it results from vascular or
      neurodegenerative mechanisms or both, is age. However, several modifiable risks
      such as cardiovascular disease, hypertension, dyslipidemia, diabetes, and obesity
      enhance the rate of cognitive decline and increase the risk of Alzheimer's
      disease in particular. The ultimate accumulation of brain pathological lesions
      may be modified by genetic influences, such as the apolipoprotein E epsilon4
      allele and the environment. Lifestyle measures that maintain or improve
      cardiovascular health, including consumption of healthy diets, moderate use of
      alcohol, and implementation of regular physical exercise are important factors
      for brain protection.

PMID- 21091954
TI  - How realistically does outdoor UV-B supplementation with lamps reflect ozone
      depletion: an assessment of enhancement errors.
AB  - Limitations in the realism of currently available lamps mean that enhancement
      errors in outdoor experiments simulating UV-B radiation effects of stratospheric
      ozone depletion can be large. Here, we assess the magnitude of such errors at two
      Finnish locations, during May and June, under three cloud conditions. First we
      simulated solar radiation spectra for normal, compared with 10% and 20% ozone
      depletion, and convoluted the daily integrated solar spectra with eight
      biological spectral weighting functions (BSWFs) of relevance to effects of UV on
      plants. We also convoluted a measured spectrum from cellulose-acetate filtered UV
      B lamps with the same eight BSWFs. From these intermediate results we calculated
      the enhancement errors. Differences between locations and months were small,
      cloudiness had only a minor effect. This assessment was based on the assumption
      that no extra enhancement compensating for shading of UV radiation by lamp frames
      is performed. Under this assumption errors between spectra are due to differences
      in the UV-B effectiveness rather than differences in the UV-A effectiveness.
      Hence, conclusions about plant growth from past UV-supplementation experiments
      should be valid. However, interpretation of the response of individual
      physiological processes is less secure, so results from some field experiments
      with lamps might need reassessment.

PMID- 21091953
TI  - Nutritional modifiers of aging brain function: use of uridine and other
      phosphatide precursors to increase formation of brain synapses.
AB  - Brain phosphatide synthesis requires three circulating compounds: docosahexaenoic
      acid (DHA), uridine, and choline. Oral administration of these phosphatide
      precursors to experimental animals increases the levels of phosphatides and
      synaptic proteins in the brain and per brain cell as well as the numbers of
      dendritic spines on hippocampal neurons. Arachidonic acid fails to reproduce
      these effects of DHA. If similar increases occur in human brain, administration
      of these compounds to patients with diseases that cause loss of brain synapses,
      such as Alzheimer's disease, could be beneficial.

PMID- 21091955
TI  - Light induced and circadian effects on retinal photoreceptor cell crystallins.
AB  - Crystallins in the retina may serve a chaperone-like protective function. In this
      study we measured mRNA levels for alpha-, beta- and gamma-crystallins in rat
      retinas following treatment with potentially damaging levels of light. We also
      determined crystallin protein patterns in photoreceptor cell rod outer segments
      (ROSs) isolated from rats exposed to intense light. Weanling albino rats were
      maintained in a dim cyclic light environment or in darkness for 40days. At P60
      animals were treated with intense visible light, for as long as 8h, beginning at
      various times of the day or night. Retinas were excised immediately after light
      treatment and used for quantitative RT-PCR, or to prepare ROSs for western
      analysis. Some eyes were frozen in OCT for crystallin immunohistochemistry.
      Intense light exposure led to increases in mRNA expression for all retinal
      crystallins and to changes in ROS crystallin immunoreactivity. These light
      induced changes were found to depend on the time of day that exposure started,
      duration of light treatment and previous light rearing history. We suggest that
      crystallin synthesis in retina exhibits a dependence on both light stress and
      circadian rhythm and that within photoreceptor cells crystallins appear to
      migrate in a light-independent, circadian fashion.

PMID- 21091956
TI  - Spectroscopic and photochemical characterization of the red-light sensitive
      photosensory module of Cph2 from Synechocystis PCC 6803.
AB  - Cyanobacterial phytochromes are a diverse family of light receptors controlling
      various biological functions including phototaxis. In addition to canonical bona
      fide phytochromes of the well characterized Cph1/plant-like clade, cyanobacteria
      also harbor phytochromes that absorb green, violet or blue light. The
      Synechocystis PCC 6803 Cph2 photoreceptor, a phototaxis inhibitor, is
      unconventional in bearing two distinct chromophore-binding GAF domains. Whereas
      the C-terminal GAF domain is most likely involved in blue-light perception, the
      first two domains correspond to a Cph1-like photosensory module lacking the PAS
      domain. Biochemical and spectroscopic studies show that this region switches
      between red (P(r) ) and far-red (P(fr) ) absorbing states. Unlike Cph1, the P(fr)
      state of Cph2 decays rapidly in darkness. Mutations close to the PCB chromophore
      further destabilize the P(fr) state without drastically affecting the
      spectroscopic features such as the quantum efficiency of P(r) ->P(fr) conversion,
      fluorescence, or the Resonance-Raman signature of the chromophore. Overall, the
      PAS-less photosensory module of Cph2 resembles Cph1 including its mode of
      isomerisation, but the P(fr) state is unstable.

PMID- 21091957
TI  - Hemolysis of red blood cells after cell washing with different automated
      technologies: clinical implications in a neonatal cardiac surgery population.
AB  - BACKGROUND: In subsets of pediatric cardiac surgery patients, red blood cells
      (RBCs) are often washed to reduce extracellular potassium (K) to avoid
      hyperkalemia, but mechanical manipulation and time delay in issuing washed
      products may increase hemolysis and K. This study's purpose was to evaluate the
      quality of washed RBCs with regard to hemolysis and extracellular K using
      different cell washers as a function of postprocessing time. STUDY DESIGN AND
      METHODS: Fresh (<4 days old) RBCs were washed on COBE 2991 blood cell processors
      (Model 1 and Model 2) or the Fresenius Continuous AutoTransfusion System (CATS),
      and K and hemolysis index (HI) were analyzed. Academic pediatric hospitals were
      surveyed to ascertain practice trends regarding indications for washing, washing
      device, and expiration time for washed RBCs. RESULTS: K concentration at 24 hours
      for units washed with the COBE devices met or exceeded prewash values. At 12
      hours, there was a significant difference (p < 0.001) in K concentration between
      all devices, with the CATS maintaining the lowest K concentration. HI increased
      immediately after wash on all devices and showed a significant difference between
      the COBE devices and CATS at times of more than 6 hours (p < 0.01). At storage
      times beyond 4 hours, hemoglobin exceeded 100 mg/dL on the COBE Model 1. Survey
      of pediatric hospitals indicated that COBE devices are commonly used, and storage
      time after washing was 12 hours or more in blood banks queried. CONCLUSIONS:
      Hemolysis levels vary among different cell washers. Decreasing the expiration
      time of units after washing may be warranted.

PMID- 21091958
TI  - Prevalence of posterior subcapsular cataracts in volunteer cytapheresis donors.
AB  - BACKGROUND: Granulocyte donors routinely receive dexamethasone orally before
      donation. Steroids may increase the risk of posterior subcapsular cataract (PSC)
      formation. STUDY DESIGN AND METHODS: We recruited 100 granulocyte donors (four or
      more granulocyte donations; any number of platelet [PLT] donations) and 100 age-
      and sex-matched PLT donors (zero to three granulocyte donations, any number of
      PLT donations) to examine the risk of PSC. PSC was assessed by a masked
      ophthalmologist and reading center lens photograph gradings or medical record
      documentation of PSC as the reason for cataract extraction. RESULTS: Fourteen
      eyes of 10 granulocyte donors and five eyes of four PLT donors had PSCs (odds
      ratio [OR], 2.82; 95% confidence interval [CI], 0.83-9.61; p = 0.10). Risk of PSC
      increased with number of granulocyte donations: compared to zero to three
      donations (4.0%), the risk for four to nine, 10 to 19, and 20 or more donations
      was 8.6% (OR, 2.25; 95% CI, 0.31-13.99; p = 0.30), 9.5% (OR, 2.53; 95% CI, 0.44
      14.20; p = 0.21), and 13.0% (OR, 3.60; 95% CI, 0.48-22.81; p = 0.11),
      respectively (p = 0.06 for trend). CONCLUSION: We did not demonstrate a
      statistically significant increased risk of PSC associated with granulocyte
      donation. However, although this makes a large risk unlikely, we cannot rule out
      a small to moderate risk and there is biologic plausibility that the steroid
      administration associated with granulocyte donation could be associated with PSC
      formation. Transfusion medicine professionals should advise granulocyte apheresis
      donors to maintain an appropriate frequency of eye examinations.

PMID- 21091959
TI  - On the number of trials needed for a stable feedback-related negativity.
AB  - Feedback-related negativity is an event-related brain potential elicited by
      negative feedback. Its properties make it a valuable tool for the assessment of
      cognitive-affective processes that are involved in feedback and reward
      processing. The present study sought to determine the minimum number of trials
      that are required to obtain a reliable FRN component using a simple gambling
      paradigm. Three independent groups of young participants and one group of old
      participants were used. In the experimental conditions with healthy young
      controls, 20 trials were sufficient to measure the optimal FRN amplitude. In
      older participants, 50 trials were needed to obtain a reliable FRN. Whereas 20
      trials would be enough to ensure a reliable FRN component in studies with
      nonclinical samples, the number of trials needed in clinical and cognitively
      impaired populations has to be determined based on the signal-to-noise ratios and
      the characteristics of the signals recorded.

PMID- 21091960
TI  - It's a word: early electrophysiological response to the character likeness of
      pictographs.
AB  - Using unfamiliar and meaningless pictographs that varied in their degree of
      similarity to Chinese characters, the current study tested whether the early
      electrophysiological response was modulated by character likeness. We measured
      P100 and N170 while 20 native Chinese speakers were viewing Chinese characters,
      drawings of objects, and pictographs. Comparisons across the three categories of
      stimuli showed that pictographs elicited a smaller N170 amplitude than did
      Chinese characters and a stronger N170 amplitude than did objects, but did not
      differ in the P100 amplitude from the other two categories. Within the category
      of pictographs, stimuli with a higher degree of character likeness elicited
      larger N170 amplitudes and shorter N170 peak latencies, and this effect was again
      not observed in P100. These results suggest that N170 is sensitive to visual
      stimuli's character likeness even though they are unfamiliar pictographs with no
      meanings or sounds.

PMID- 21091961
TI  - Nocturnal haemoglobin oxygen saturation variability is associated with vitamin C
      deficiency in Tanzanian children with sickle cell anaemia.
AB  - AIM: To compare pulse oximetry in children with sickle cell anaemia (SCA) and
      controls and test the hypothesis that vitamin C deficiency (VCD; <11.4 MUmol/L)
      is associated with nocturnal haemoglobin oxygen desaturation in SCA. METHODS: We
      undertook nocturnal and daytime pulse oximetry in 23 children with SCA (median
      age 8 years) with known steady-state plasma vitamin C concentrations and 18
      siblings (median 7 years). RESULTS: Median nocturnal delta 12 s index (delta12
      s), a measure of haemoglobin oxygen saturation (SpO(2)) variability, was 0.38
      (interquartile range 0.28-0.51) in SCA and 0.35 (0.23-0.48) in controls, with
      9/23 and 6/18, respectively, having a delta12 s >0.4, compatible with obstructive
      sleep apnoea (OSA). Eleven of twenty-three with SCA had VCD; logged vitamin C
      concentrations showed a 66% decrease per 0.1 unit increase in delta12 s ([95% CI 
      86%, -15%]; p=0.023) and delta12 s >0.4 was associated with VCD (odds ratio 8.75
      [1.24-61.7], p=0.029). Daytime and mean nocturnal SpO(2) were lower in SCA but
      there was no association with vitamin C. CONCLUSION: Obstructive sleep apnoea
      (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is
      common in Tanzanian children and associated with vitamin C Deficiency in SCA. The
      direction of causality could be determined by comparing OSA treatment with
      vitamin C supplementation.

PMID- 21091962
TI  - Breastfeeding after assisted conception: a prospective cohort study.
AB  - AIM: The aims were to investigate the prevalence of breastfeeding after
      conception with assisted reproductive technology (ART) and identify risk factors
      for breastfeeding duration <6 weeks and cessation of breastfeeding before the
      baby is 8 months old. METHODS: A consecutive cohort of women who had conceived at
      one of two ART centres in Melbourne, Australia, was recruited in early pregnancy.
      The women completed telephone interviews and postal questionnaires in pregnancy
      and 3, 8 and 18 months after the birth. RESULTS: Of 239 eligible women, 183 (77%)
      agreed to take part. Participants were more likely than the general population of
      childbearing Australian women to initiate breastfeeding (89% vs 83.3%, p=0.05)
      but by 3 months, a smaller proportion was breastfeeding exclusively (46% vs
      57.3%, p=0.004). The proportions not providing any breast milk at 6 weeks and 8
      months were 23% and 57%, respectively. More anxiety in late pregnancy and sub
      optimal breastfeeding advice predicted breastfeeding duration <6 weeks and
      breastfeeding cessation before 8 months. CONCLUSION: The predictors of less
      favourable breastfeeding outcomes after ART identified may be modifiable.
      Antenatal strategies to reduce anxiety in pregnancy and postnatal strategies to
      ensure consistent breastfeeding advice may improve breastfeeding outcomes among
      women who give birth after ART.

PMID- 21091963
TI  - Robotic renal transplantation: first European case.
AB  - A kidney from a 56-year-old mother was transplanted to her 37-year-old daughter
      laparoscopically using the daVinci HDSi surgical system. The kidney was
      introduced into the abdomen through a 7-cm suprapubic incision used also for the
      uretero-vescical anastomosis. Vascular anastomoses were carried out through a
      total of three additional ports. Surgery lasted 154 min, including 51 min of warm
      ischemia of the graft. Urine production started immediately after graft
      reperfusion. Renal function remains optimal at the longest follow-up of 3 months.
      The technique employed in this case is discussed in comparison with the only
      other two contemporary experiences, both from the USA. Furthermore, possible
      advantages and disadvantages of robotics in kidney transplantation are discussed
      extensively. We conclude that the daVinci surgical system allows the performance
      of kidney transplantation under optimal operative conditions. Further experience
      is needed, but it is likely that solid organ transplantation will not remain
      immune to robotics.

PMID- 21091964
TI  - Robotic navigation in catheter ablation for paroxysmal atrial fibrillation:
      midterm efficacy and predictors of postablation arrhythmia recurrences.
AB  - INTRODUCTION: Remote navigation systems represent a novel strategy for catheter
      ablation of atrial fibrillation (AF). The goal of this study is to describe a
      single-center experience with the electromechanical robotic system (Sensei,
      Hansen Medical) in treatment of patients with paroxysmal AF. METHODS: Out of 200
      patients who underwent robotically guided ablation for AF between 2007 and 2009
      at our institute, 100 patients (29 women, age 56.5 +/- 10 years) had paroxysmal
      AF refractory to antiarrhythmic drugs. Electroanatomic mapping using NavX system
      (St. Jude Medical) provided anatomical shell for subsequent circumferential
      ablation with robotic catheter (Artisan) loaded with a 3.5-mm, open-irrigation,
      cooled-tip ablation catheter. RESULTS: A mean of 69 radiofrequency current
      applications (duration 2082 +/- 812 seconds) were delivered to achieve
      circumferential electrical isolation of pulmonary venous antra. Total procedural
      time reached 222 +/- 54 minutes. The mean fluoroscopic time was 11.9 +/- 7.8
      minutes. There were no major procedure-related complications. After a median
      follow-up of 15 months (range 3-28 months), 63% of the patients were free from
      any atrial arrhythmias >= 30 seconds after the single procedure. Success rate
      increased to 86% after 1.2 procedures. Multivariate analysis revealed that only
      predictor of recurrent AF/AT was shorter overall procedural time (207 +/- 36 vs
      236 +/- 64 minutes in patients with and without recurrences, respectively, P =
      0.0068). CONCLUSIONS: This study demonstrates feasibility and safety of robotic
      navigation in catheter ablation for paroxysmal AF. Midterm follow-up documents
      success rate comparable to other technologies and potential for improvement in
      more extensive ablation along the ridges with thicker myocardium.

PMID- 21091965
TI  - Defibrillation thresholds in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Defibrillation threshold (DFT) testing is performed in part to ensure
      an adequate safety margin for the termination of spontaneous ventricular
      arrhythmias. Left ventricular mass is a predictor of high DFTs, so patients with
      hypertrophic cardiomyopathy (HCM) are often considered to be at risk for
      increased defibrillation energy requirements. However, there are little
      prospective data addressing this issue. OBJECTIVE: To assess DFTs in patients
      with HCM and evaluate the clinical predictors of elevated DFTs. METHODS: Eighty
      nine consecutive patients with HCM and 600 control patients with ischemic or
      nonischemic cardiomyopathy underwent a uniform modified step-down DFT testing
      protocol. DFT was compared between the control and HCM populations. Predictors of
      elevated DFT were evaluated in the HCM group. RESULTS: There was no difference in
      DFT between HCM and control groups (10.4 +/- 5.8 J vs 11.2 +/- 5.6 J,
      respectively). Among patients with HCM, clinical parameters such as left
      ventricular ejection fraction, interventricular septal thickness, left
      ventricular mass, and QRS duration were not predictive of an elevated DFT. Only 3
      patients (3.4%) with HCM had a DFT >20 J. CONCLUSION: Patients with HCM do not
      have elevated DFTs as compared to more typical populations undergoing implantable
      cardioverter-defibrillator implant; high-energy devices or complex lead systems
      are not needed routinely in this population.

PMID- 21091966
TI  - Cryoballoon ablation of atrial fibrillation.
AB  - Pulmonary vein isolation using a cryoballoon has evolved into a relatively simple
      alternative for point-by-point radiofrequency ablation because this technology
      theoretically allows for PV isolation with a single application. Recent clinical
      studies indicate a high efficacy rate of the procedure; however, the incidence of
      the most common complication-phrenic nerve palsy (PNP)-has been reported in up to
      11.2% of cases. Based on the present data, PNP is mainly associated with the use
      of the smaller 23 mm balloon. Very recently, it became evident that cryoballoon
      ablation may be associated with PV stenosis. Thus, the use of cryoballoon
      technology needs to be combined with a strategy aiming for maximal patient
      safety. The "single big (28 mm) cryoballoon technique" is a straightforward
      single-device strategy to deploy cryothermal lesions proximal to the PV ostium at
      the antrum level, thereby reducing the risk of collateral damage. Using this
      technique the endpoint of complete PV isolation was achieved in 97% of patients
      in our laboratory. PNP was observed in 4.4% of patients and resolved within 12
      months in the majority of cases. In the future, development of an even bigger (32
      mm) cryoballoon may further increase procedural safety by reducing the risk of
      PNP or PV stenosis.

PMID- 21091967
TI  - Statins, inflammation, oxidative stress, and atrial fibrillation.

PMID- 21091968
TI  - OptiVol fluid index: does an association with ventricular arrhythmias hold water?

PMID- 21091969
TI  - Utility of distinctive local electrogram pattern and aortographic anatomical
      position in catheter manipulation at coronary cusps.
AB  - BACKGROUND: The coronary cusps have recently become target sites for
      radiofrequency catheter ablation of both outflow tract ventricular arrhythmias
      originating near the coronary cusps (CC-VA) and atrial tachyarrhythmias such as
      focal atrial tachycardia originating near the noncoronary cusp (NCC-AT). However,
      the relation between local electrograms recorded at each CC during sinus rhythm
      and their anatomical position as assessed by aortography has not yet been
      systematically described. METHODS AND RESULTS: In 28 patients undergoing RFCA for
      CC-VA or NCC-AT, amplitudes of the atrial and ventricular potentials at the CCs
      were measured during sinus rhythm, and the atrial/ventricular (A/V) potential
      ratio was computed. Relative positions of the CCs were assessed by aortography in
      2 X-ray projections. In the right (RCC) and left coronary cusps (LCC), amplitudes
      of the ventricular potential were larger than those of the atrial potential,
      leading to an A/V ratio <1 in all patients (0.08 +/- 0.10, 0.32 +/- 0.21,
      respectively). In contrast, in the NCC, the amplitude of the atrial potential was
      larger than the ventricular potential, leading to a higher A/V ratio relative to
      the CCs (5.7 +/- 2.6, P < 0.0001). Aortography demonstrated the rightward and
      anterior location of the RCC, the leftward and superior location of the LCC, and
      the inferior and posterior location of the NCC. CONCLUSIONS: Awareness of the
      distinctive local electrogram pattern of each CC and their positions on
      aortography should lead to safer and more effective catheter ablation at the CCs.

PMID- 21091970
TI  - Cost-effectiveness of specialized multidisciplinary heart failure clinics in
      Ontario, Canada.
AB  - BACKGROUND: Specialized multidisciplinary clinics have been shown to reduce
      mortality in heart failure (HF). Our objective was to evaluate the cost
      effectiveness of this model of care delivery. METHODS: We performed a cost
      effectiveness analysis, with a 12-year time horizon, from the perspective of the
      Ontario Ministry of Health and Long-term Care, comparing a standard care cohort,
      consisting of all patients admitted to hospital with HF in 2005, to a
      hypothetical cohort treated in HF clinics. Survival curves describing the natural
      history of HF were constructed using mortality estimates from the Enhanced
      Feedback for Effective Cardiac Treatment (EFFECT) study. Survival benefits and
      resource uptake associated with HF clinics were estimated from a meta-analysis of
      published trials. HF clinics costs were obtained by costing a representative
      clinic in Ontario. Health-related costs were determined through linkage to
      administrative databases. Outcome measures included life expectancy (years),
      costs (in 2008 Canadian dollars) and the incremental cost-effectiveness ratio
      (ICER). RESULTS: HF clinics were associated with a 29% reduction in all-cause
      mortality (risk ratio [RR] 0.71; 95% confidence interval [CI] 0.56-0.91) but a
      12% increase in hospitalizations (RR 1.12; 95% CI 0.92-1.135). The cost of care
      in HF clinics was $52 per 30 patient-days. Projected life-expectancy of HF clinic
      patients was 3.91 years, compared to 3.21 years for standard care. The 12-year
      cumulative cost per patient in the HF clinic group was $66,532 versus $53,638 in
      the standard care group. The ICER was $18,259/life-year gained. CONCLUSIONS: HF
      clinics appear to be a cost effective way of delivering ambulatory care to HF
      patients.

PMID- 21091971
TI  - Hepatitis C virus: from discovery to eradication in 40 years?

PMID- 21091972
TI  - Genotypic analysis of genes associated with transmission and drug resistance in
      the Beijing lineage of Mycobacterium tuberculosis.
AB  - The Beijing genotype of Mycobacterium tuberculosis is an endemic lineage in East
      Asia that has disseminated worldwide. It is a major health concern, as it is
      geographically widespread and is considered to be hypervirulent. To elucidate its
      genetic diversity in Taiwan, phylogenetic reconstruction was performed using 338
      M. tuberculosis Beijing family clinical isolates. Region-of-difference analysis
      revealed the strains from Taiwan to be distributed among six subgroups of a
      phylogenetic tree. Synonymous single nucleotide polymorphisms at 10 chromosomal
      positions were also analysed. Among the 338 isolates analysed for single
      nucleotide polymorphisms by using mass spectrometry, the most frequent strain
      found was ST10 (53.3%), followed by ST19 (14.8%) and ST22 (14.5%). Tests of drug
      resistance showed that the sublineages ST10, ST19 and ST26 were over-represented
      in the multidrug-resistant population. The presence of mutations in putative
      genes coding for DNA repair enzymes, which could confer a mutator phenotype to
      facilitate spreading of the pathogen, did not demonstrate an association with
      multidrug resistance. Therefore, the DNA repair genes may be involved in
      transmission but not in drug resistance.

PMID- 21091973
TI  - Bilateral vs unilateral laparoscopic intrafascial nerve-sparing radical
      prostatectomy: evaluation of surgical and functional outcomes in 457 patients.
AB  - Study Type - Therapy (case series). LEVEL OF EVIDENCE:  4. What's known on the
      subject? and What does the study add? Bilateral nerve-sparing radical
      prostatectomy still represents an issue for urologists as the indications to
      perform it depend oft from the personal clinical experience. Moreover, until now
      data concerning bilateral and unilateral laparoscopic nerve-sparing radical
      prostatectomy have been limited. This study states that bilateral laparoscopic
      intrafascial nerve-sparing technique results in superior functional outcomes when
      compared with unilateral nsLRP and it suggests to prefer a bilateral nerve
      sparing technique in younger patients with low-risk, organ-confined prostate
      cancer. OBJECTIVE: To evaluate the surgical and functional outcomes in bilateral
      and unilateral nerve-sparing laparoscopic radical prostatectomy (nsLRP). PATIENTS
      AND METHODS: Between January 2005 and May 2009, 457 nsLRP were performed at our
      clinic. In all, 250 patients underwent a bilateral nsLRP and 207 patients
      underwent an unilateral nsLRP. One surgeon performed all the operations. All
      patients presented at biopsy a localized prostate cancer. Demographic data and
      perioperative and postoperative measurements and outcomes were compared. RESULTS:
      The operative times for bilateral nsLRP and unilateral nsLRP were 165 +/- 45 min
      and 130 +/- 25 min, respectively. The mean intra-operative blood loss was 450 +/-
      300 mL and 270 +/- 160 mL in the bilateral and unilateral nsLRP groups with a
      transfusion rate of 3% and 1%, respectively (P = 0.013). Conversion to open
      surgery was never deemed necessary. Postoperatively, the mean Gleason Score after
      nsLRP and distribution of tumour stages was similar in the two groups, and the
      frequency of positive margins in both groups did not present any statistically
      significant difference. At 12 months, a complete continence was reported in 97%
      of patients who underwent a bilateral nsLRP and in 88% of patients of the
      unilateral nsLRP group. At that time, 69% in the bilateral nsLRP and 43% in the
      unilateral nsLRP groups reported the ability to engage in sexual intercourse.
      CONCLUSION: The bilateral laparoscopic intrafascial nerve-sparing technique
      results in superior functional outcomes with regard to urinary continence and
      sexual potency, when compared with unilateral nsLRP, reporting similar
      oncological outcomes.

PMID- 21091974
TI  - Oral complications after lingual mucosal graft harvesting for urethroplasty in
      110 cases.
AB  - OBJECTIVE * This study was to evaluate donor-site complications of lingual
      mucosal graft harvesting for substitution urethroplasty. PATIENTS AND METHODS *
      110 patients with anterior urethral strictures or hypospadias underwent lingual
      mucosal grafts (LMGs) urethroplasty. Dual LMGs were harvested from both sites
      separately or a long mucosal graft was harvested from one side to other side of
      tongue in 29 patients (group one); a shorter mucosal graft was harvested from one
      side of tongue in 81 patients (group two). A standard proforma (Appendix) was
      used for all patients. RESULTS * The mean follow up time was 22 months (range
      6~41). At six months follow-up, numbness of tongue was reported in 19 patients
      (17.27%), parageusias in six (5.45%) and slurring of speech in 9 (8.18%). *
      Ninety-six patients were followed up for more than 12 mo. Numbness in operative
      area of tongue was documented in seven patients (7.29%), parageusias in three
      (3.13%) and slurred speech in three (3.13%). * None of these complications
      occurred in the six pediatric cases (<14 year) with a history of failed
      hypospadias repair. CONCLUSIONS * LMGs urethroplasty, as most patients, were
      satisfied, but there were certain complications that have not been previously
      described in the literature. * Most oral complications subsided gradually within
      the first year.

PMID- 21091975
TI  - Urothelial lesions with inverted growth patterns: histogenesis, molecular genetic
      findings, differential diagnosis and clinical management.
AB  - A number of well-recognized urothelial lesions with inverted morphology occur in
      the urinary bladder. Some are so common that they are considered normal variants
      of urothelium, whereas others are rare. It is important for the surgical
      pathologist to recognize these lesions and their overlapping morphological
      features, because in some cases establishing an accurate diagnosis is
      challenging. In this article, we review the spectrum of inverted urothelial
      lesions of the bladder. Emphasis is placed on differential diagnosis, molecular
      genetic findings, morphology and histogenesis.

PMID- 21091976
TI  - Long-term overall survival and metastasis-free survival for men with prostate
      specific antigen-recurrent prostate cancer after prostatectomy: analysis of the
      Center for Prostate Disease Research National Database.
AB  - OBJECTIVE: * To describe metastasis-free survival (MFS) and overall survival (OS)
      among men with prostate-specific antigen (PSA)-recurrent prostate cancer after
      radical prostatectomy who did not receive additional therapy until metastasis,
      using a multicentre database capturing a wide ethnic mix. PATIENTS AND METHODS: *
      A retrospective analysis of the Center for Prostate Disease Research National
      Database (comprised of five US military hospitals and one civilian centre) was
      performed for patients with PSA relapse (>= 0.2 ng/mL) after radical
      prostatectomy who had no additional therapy until the time of radiographic
      metastatic disease. * We investigated factors influencing metastasis and all
      cause mortality using univariate and multivariate Cox regression analysis.
      RESULTS: * There were a total of 346 men who underwent radical prostatectomy
      between May 1983 and November 2008 and fulfilled the entry criteria. All patients
      had information on survival and 190 men had information on metastasis. Among
      patients with survival data (n= 346), 10-year OS was 79% after a median follow-up
      of 8.6 years from biochemical recurrence. * Among men with metastasis data (n=
      190), 10-year MFS was 46% after a median follow-up of 7.5 years. * In Cox
      regressions, four clinical factors (Gleason score, pathological stage, time to
      PSA relapse and PSA doubling time), as well as age, were predictive of OS and/or
      MFS in univariate analysis, although only PSA doubling time (>= 9 vs 3-8.9 vs <3
      months) remained independently predictive of these outcomes in multivariate
      analysis (P < 0.001). CONCLUSIONS: * This multicentre multi-ethnic dataset shows
      that OS and MFS can be extensive for men with PSA-recurrent prostate cancer, even
      in the absence of further therapy before metastasis. * This unique patient
      cohort, the second largest of its type after the Johns Hopkins cohort, confirms
      that PSA doubling time is the strongest determinant of OS and MFS in men with PSA
      recurrent disease. * Longer follow-up and more events will be required to
      determine whether other variables may also contribute to these outcomes.

PMID- 21091977
TI  - Endothelin-1: a predictor of extracapsular extension in clinically localized
      prostate cancer?
AB  - OBJECTIVE: To assess the value of endothelin-1 (ET-1) expression in predicting
      extracapsular extension (ECE) in clinically localized prostate cancer (PCa).
      PATIENTS AND METHODS: ET-1 expression was determined by immunohistochemistry on
      archival needle biopsies (NBs) from 94 patients (49 pT2 and 45 pT3a) who
      underwent radical prostatectomy (RP) for clinical T1-T2 PCa. Each sample was
      analysed independently by two pathologists blinded to the clinical data. RESULTS:
      In univariate analysis, high ET-1 expression in NBs, pre-operative prostate
      specific antigen (PSA) level >10 ng/ml, percentage of positive biopsy cores and
      NB Gleason score >=7 were significantly associated with ECE as determined on
      subsequent RP. No significant association was found between clinical stage and
      ECE. In multivariate analysis, there was a significant association with high ET-1
      expression in NBs (p = 0.006), pre-operative PSA level >10 ng/ml (p = 0.049), and
      NB Gleason score >=7 (p = 0.002). These three pre-operative factors combined
      provided the best model for predicting ECE with 93.3% sensitivity, 49%
      specificity, 62.5% positive predictive value, 88.9% negative predictive value.
      The combination yielded a higher concordance index (0.760 vs 0.720) and offered a
      higher log partial likelihood than the same model without ET1 (112.8 vs 105.7, p
      = 0.01). CONCLUSIONS: ET-1 expression was strongly associated with ECE and, when
      combined with pre-operative PSA level and Gleason score, improved the predictive
      accuracy of pre-operative NBs. Its assessment in patients with localized PCa
      might be useful when making treatment decisions. Further studies with
      standardisation of immunohistochemical staining and multi-institutional
      validation are now needed to establish the appropriate use of ET-1 staining in
      PCa staging and to evaluate inter-observer reproducibility.

PMID- 21091978
TI  - Paraoxonase-1 is only present in traceable amounts in seminal fluid and does not
      show any relationship with male subfertility.
AB  - Study Type - Aetiology (case series). LEVEL OF EVIDENCE: 4. What's known on the
      subject? and What does the study add? Oxidative stress seems to be one of the
      biochemical causes of defective sperm function. Paraoxonases are antioxidant
      enzymes that degrade lipid peroxides. There is a paucity of data on the possible
      role played by these enzymes in the pathophysiology of male sub-fertility. The
      present study shows that testicular tissue of sub-fertile patients clearly
      expresses paraoxonases-1, 2, and 3. These findings suggest a role for these
      enzymes in the protection against lipid peroxidation inside the cell. However,
      the concentration and activity of paraoxonase-1 in semen are negligible and are
      probably the result of cellular catabolism, with no significant biological
      function. OBJECTIVE: To characterise the immunohistochemical sites of paraoxonase
      (PON) 1, PON2 and PON3 in human testicular tissue, and to analyse PON1 levels in
      semen, aiming to investigate the role played by these enzymes in the
      pathophysiology of male subfertility. PATIENTS AND METHODS: The present study was
      performed in 41 semen samples from normal donors and in 52 semen samples and ten
      testicle biopsies from patients who were being evaluated for causes of
      subfertility. RESULTS: Immunohistochemical analyses showed high levels of PON1
      and PON3 expression in testicular tissue. PON2 expression was also detected,
      albeit at weaker levels. Oxidative stress indicators in biopsies were low and
      localized in some specific areas of the seminiferous tubules. PON1 was detected
      in seminal fluid at very low levels but with no significant differences between
      patients and controls. Receiver-operating characteristic analysis showed a low
      diagnostic power of semen PON1 levels. CONCLUSIONS: The present study shows high
      protein expression levels of PON1, PON2 and PON3 in testicular cells. The
      concentrations and activities of PON1 in semen are negligible and are probably
      the result of cellular catabolism, with no significant biological function in the
      testes.

PMID- 21091979
TI  - The association between renal cell carcinoma and multiple myeloma: insights from
      population-based data.
AB  - OBJECTIVE: * To evaluate the hypothesis of an association between renal cell
      carcinoma and multiple myeloma. PATIENTS AND METHODS: * Data from nine population
      based registries in the Surveillance, Epidemiology and End Results programme were
      used to evaluate two separate cohorts of patients diagnosed between 1973 and
      2006: patients diagnosed with renal cell carcinoma as a primary malignancy (n=
      57,190) and patients diagnosed with multiple myeloma as a primary malignancy (n=
      34,156). * We estimated standardized incidence ratios (SIRs) with corresponding
      95% confidence intervals (CIs) by dividing the number of observed cases of
      multiple myeloma within the renal cell carcinoma cohort and the number of renal
      cell carcinoma cases within the multiple myeloma cohort by the number of expected
      cases for each malignancy in the US general population. RESULTS: * The renal cell
      carcinoma cohort yielded 88 multiple myeloma cases during 293,511 person-years of
      follow up. Patients with renal cell carcinoma had a higher relative risk of
      multiple myeloma than the general population (SIR = 1.51, 95% CI 1.21-1.85). *
      The multiple myeloma cohort yielded 69 renal cell carcinoma cases during 100,804
      person-years of follow up. Patients with multiple myeloma had a higher relative
      risk of renal cell carcinoma than the general population (SIR = 1.89, 95% CI 1.47
      2.40). CONCLUSION: * Our analyses revealed a bidirectional association between
      renal cell carcinoma and multiple myeloma, which typically indicates shared risk
      factors.

PMID- 21091980
TI  - Interventions for preventing and managing aggressive patients admitted to an
      acute hospital setting: a systematic review.
AB  - BACKGROUND: Violence in health care has been widely reported and health care
      workers, particularly nurses in acute care settings, are ill-equipped to manage
      patients who exhibit aggressive traits. AIM: The aim of this systematic review
      was to establish best practice in the prevention and management of aggressive
      behaviours in patients admitted to acute hospital settings. DATA SOURCES: An
      extensive search of the major databases was conducted from 1990 to 2007. The
      search included published and unpublished studies and papers in English. REVIEW
      METHODS: This review considered any quantitative research study design that
      evaluated the effectiveness of interventions in the prevention and management of
      patients who exhibit aggressive behaviours in an acute hospital setting. Each
      included study was quality assessed by two independent reviewers and data were
      extracted using the relevant tools developed by the Joanna Briggs Institute.
      RESULTS: Ten studies met the inclusion criteria and were included in the review.
      The evidence identified from the studies includes: the benefit of education and
      training of acute care nurses in aggression management techniques; use of "as
      required" medications is effective in minimising harm to patients and staff; and
      that specific interventions such as physical restraint may play a role in
      managing aggressive behaviours from patients in the acute care setting.
      CONCLUSIONS: This review makes several recommendations for the prevention and
      management of aggressive behaviours in acute hospital patients. However, due to
      the lack of high-quality studies conducted in the acute care setting there is
      huge scope for future research in this area.

PMID- 21091981
TI  - Experimental evolution exposes female and male responses to sexual selection and
      conflict in Tribolium castaneum.
AB  - Between-individual variance in potential reproductive rate theoretically creates
      a load in reproducing populations by driving sexual selection of male traits for
      winning competitions, and female traits for resisting the costs of multiple
      mating. Here, using replicated experimental evolution under divergent operational
      sex ratios (OSR, 9:1 or 1:6 ?:?) we empirically identified the parallel
      reproductive fitness consequences for females and males in the promiscuous flour
      beetle Tribolium castaneum. Our results revealed clear evidence that sexual
      conflict resides within the T. castaneum mating system. After 20 generations of
      selection, females from female-biased OSRs became vulnerable to multiple mating,
      and showed a steep decrease in reproductive fitness with an increasing number of
      control males. In contrast, females from male-biased OSRs showed no change in
      reproductive fitness, irrespective of male numbers. The divergence in
      reproductive output was not explained by variation in female mortality. Parallel
      assays revealed that males also responded to experimental evolution: individuals
      from male-biased OSRs obtained 27% greater reproductive success across 7-day
      competition for females with a control male rival, compared to males from the
      female-biased lines. Subsequent assays suggest that these differences were not
      due to postcopulatory sperm competitiveness, but to precopulatory/copulatory
      competitive male mating behavior.

PMID- 21091982
TI  - Milk banks through the lens of Muslim scholars: one text in two contexts.
AB  - When Muslims thought of establishing milk banks, religious reservations were
      raised. These reservations were based on the concept that women's milk creates
      'milk kinship' believed to impede marriage in Islamic Law. This type of kinship
      is, however, a distinctive phenomenon of Arab tradition and relatively unknown in
      Western cultures. This article is a pioneer study which fathoms out the
      contemporary discussions of Muslim scholars on this issue. The main focus here is
      a religious guideline (fatwa) issued in 1983, referred to in this article as 'one
      text', by the Egyptian scholar Yusuf al-Qaradawi who saw no religious problem in
      establishing or using these banks. After a number of introductory remarks on the
      'Western' phenomenon of milk banks and the 'Islamic' phenomenon of 'milk
      kinship', this article analyses the fatwa of al-Qaradawi 'one text' and
      investigates the 'two contexts' in which this fatwa was discussed, namely, the
      context of the Muslim world and that of Muslim minorities living in the West. The
      first context led to rejecting the fatwa and refusing to introduce the milk
      banking system in the Muslim world. The second context led to accepting this
      system and thus allowing Muslims living in the West to donate and receive milk
      from these banks. Besides its relevance to specialists in the fields of Islamic
      studies, anthropology and medical ethics, this article will also be helpful to
      physicians and nurses who deal with patients of Islamic background.

PMID- 21091983
TI  - Low endotoxic activity of lipopolysaccharides isolated from Bradyrhizobium,
      Mesorhizobium, and Azospirillum strains.
AB  - The endotoxic activities of lipopolysaccharides (LPS) isolated from different
      strains of rhizobia and rhizobacteria (Bradyrhizobium, Mesorhizobium, and
      Azospirillum) were compared to those of Salmonella enterica sv. Typhimurium LPS.
      The biological activity of all the examined preparations, measured as Limulus
      lysate gelation, production of tumor necrosis factor (TNF), interleukin-1beta (IL
      1beta), and interleukin-6 (IL-6), and nitrogen oxide (NO) induction in human
      myelomonocytic cells (line THP-1), was considerably lower than that of the
      reference enterobacterial endotoxin. Among the rhizobial lipopolysaccharides, the
      activities of Mesorhizobium huakuii and Azospirillum lipoferum LPSs were higher
      than those of the LPS preparations from five strains of Bradyrhizobium. The weak
      endotoxic activity of the examined preparations was correlated with differences
      in lipid A structure compared to Salmonella.

PMID- 21091984
TI  - Characterization of T helper (Th)1- and Th2-type immune responses caused by
      baculovirus-expressed protein derived from the S2 domain of feline infectious
      peritonitis virus, and exploration of the Th1 and Th2 epitopes in a mouse model.
AB  - Feline infectious peritonitis virus (FIPV) may cause a lethal infection in cats.
      Antibody-dependent enhancement (ADE) of FIPV infection has been recognized, and
      cellular immunity is considered to play an important role in preventing the onset
      of feline infectious peritonitis. In the present study, whether or not the T
      helper (Th)1 epitope was present in the spike (S)2 domain was investigated, the
      ADE epitope being thought to be absent from this domain. Three kinds of protein
      derived from the C-terminal S2 domain of S protein of the FIPV KU-2 strain were
      developed using a baculovirus expression system. These expressed proteins were
      the pre-coil region which is the N-terminal side of the putative fusion protein
      (FP), the region from FP to the heptad repeat (HR)2 (FP-HR2) region, and the
      inter-helical region which is sandwiched between HR1 and HR2. The ability of
      three baculovirus-expressed proteins to induce Th1- and Th2-type immune responses
      was investigated in a mouse model. It was shown that FP-HR2 protein induced
      marked Th1- and Th2-type immune responses. Furthermore, 30 peptides derived from
      the FP-HR2 region were synthesized. Five and 16 peptides which included the Th1
      and Th2 epitopes, respectively, were identified. Of these, four peptides which
      included both Th1 and Th2 epitopes were identified. These findings suggest that
      the identification of Th1 epitopes in the S2 domain of FIPV has important
      implications in the cat.

PMID- 21091985
TI  - Intracellular localization of human immunodeficiency virus type 1 Gag and GagPol
      products and virus particle release: relationship with the Gag-to-GagPol ratio.
AB  - Human immunodeficiency virus (HIV) Gag precursor protein is cleaved by viral
      protease (PR) within GagPol precursor protein to produce the mature matrix (MA),
      capsid, nucleocapsid, and p6 domains. This processing is termed maturation and
      required for HIV infectivity. In order to understand the intracellular sites and
      mechanisms of HIV maturation, HIV molecular clones in which Gag and GagPol were
      tagged with FLAG and hemagglutinin epitope sequences at the C-termini,
      respectively were made. When coexpressed, both Gag and GagPol were incorporated
      into virus particles. Temporal analysis by confocal microscopy showed that Gag
      and GagPol were relocated from the cytoplasm to the plasma membrane. Mature
      cleaved MA was observed only at sites on the plasma membrane where both Gag and
      GagPol had accumulated, indicating that Gag processing occurs during Gag/GagPol
      assembly at the plasma membrane, but not during membrane trafficking.
      Fluorescence resonance energy transfer imaging suggested that these were the
      primary sites of GagPol dimerization. In contrast, with overexpression of GagPol
      alone an absence of particle release was observed, and this was associated with
      diffuse distribution of mature cleaved MA throughout the cytoplasm. Alteration of
      the Gag-to-GagPol ratio similarly impaired virus particle release with aberrant
      distributions of mature MA in the cytoplasm. However, when PR was inactive, it
      seemed that the Gag-to-GagPol ratio was not critical for virus particle release
      but virus particles encasing unusually large numbers of GagPol molecules were
      produced, these particles displaying aberrant virion morphology. Taken together,
      it was concluded that the Gag-to-GagPol ratio has significant impacts on either
      intracellular distributions of mature cleaved MA or the morphology of virus
      particles produced.

PMID- 21091986
TI  - Staphylococcal enterotoxin A: a candidate for the amplification of physiological
      immunoregulatory responses in the gut.
AB  - Staphylococcal enterotoxin A (SEA) is one of the bacterial products tested for
      modulation of unwanted immune responses. Of all the staphylococcal enterotoxins,
      SEA is the most potent stimulator of T cells. When administered orally, SEA acts
      as a superantigen (SA), producing unspecific stimulation of intra-epithelial
      lymphocytes (IELs) in the intestinal mucosa. This stimulation results in
      amplification of the normal local immunologic responses, which are mainly
      regulatory. This amplification is based on increased local production of IFN
      gamma by IELs, which acts on the nearby enterocytes. As a result, the enterocytes
      produce large amounts of tolerosomes, cellular corpuscles which detach themselves
      from the basal poles of the enterocytes and contain antigenic peptides that are
      conditioned to be interpreted as tolerogenic by the gut immune system.
      Tolerosomes are physiologically produced as a response to dietary peptides; it is
      already known that enterocytes posses the molecular mechanisms for processing
      peptides in a similar manner to lymphocytes. The fate of tolerosomes is not
      precisely known, but it seems that they merge with intestinal dendritic cells,
      conveying to them the information that orally administered peptides must be
      interpreted as tolerogens. SEA can stimulate this mechanism, thus favoring the
      development of tolerance to peptides/proteins administered subsequently via the
      oral route. This characteristic of SEA might be useful in therapy for regulating
      immune responses. The present paper reviews the current status of research
      regarding the impact of SEA on the enteric immune system and its potential use in
      the treatment of allergic and autoimmune diseases.

PMID- 21091988
TI  - Noncardiac chest pain: an unsatisfactory 'diagnosis'?

PMID- 21091987
TI  - Avoiding hyperoxemia during neonatal resuscitation: time to response of different
      SpO2 monitors.
AB  - AIM: To assess the time to obtain reliable oxygen saturation readings by
      different pulse oximeters during neonatal resuscitation in the delivery room or
      NICU. METHODS: Prospective study comparing three different pulse oximeters:
      Masimo Radical-7 compared simultaneously with Ohmeda Biox 3700 or with Nellcor
      N395, in newborn infants who required resuscitation. Members of the research team
      placed the sensors for each of the pulse oximeters being compared simultaneously,
      one sensor on each foot of the same baby. Care provided routinely, without
      interference by the research team. The time elapsed until a reliable SpO2 was
      obtained was recorded using a digital chronometer. Statistical comparisons
      included chi-square and student's T-test. RESULTS: Thirty-two infants were
      enrolled; median gestational age 32 weeks. Seventeen paired measurements were
      made with the Radical-7 and Biox 3700; mean time to a stable reading was 20.2+/-7
      sec for the Radical-7 and 74.2+/-12 sec for the Biox 3700 (p=0.02). The Radical-7
      and the N- 395 were paired on 15 infants; the times to obtain a stable reading
      were 20.9+/-4 sec and 67.3+/-12 sec, respectively (p=0.03). CONCLUSION: The time
      to a reliable reading obtained simultaneously in neonatal critical situations
      differs by the type of the pulse oximeter used, being significantly faster with
      Masimo Signal Extraction Technology. This may permit for better adjustments of
      inspired oxygen, aiding in the prevention of damage caused by unnecessary
      exposure to high or low oxygen.

PMID- 21091989
TI  - Hepatitis B virus DNA and hepatocellular carcinoma recurrence after resection:
      the lower, the better!

PMID- 21091990
TI  - Autofluorescence imaging: as a new method for predicting metachronous gastric
      cancer.

PMID- 21091991
TI  - Mechanisms of alcoholic pancreatitis.
AB  - Alcoholic pancreatitis is a major complication of alcohol abuse. The risk of
      developing pancreatitis increases with increasing doses of alcohol, suggesting
      that alcohol exerts dose-related toxic effects on the pancreas. However, it is
      also clear that only a minority of alcoholics develop the disease, indicating
      that an additional trigger may be required to initiate clinically evident
      pancreatic injury. It is now well established that alcohol is metabolized by the
      pancreas via both oxidative and non-oxidative metabolites. Alcohol and its
      metabolites produce changes in the acinar cells, which may promote premature
      intracellular digestive enzyme activation thereby predisposing the gland to
      autodigestive injury. Pancreatic stellate cells (PSCs) are activated directly by
      alcohol and its metabolites and also by cytokines and growth factors released
      during alcohol-induced pancreatic necroinflammation. Activated PSCs are the key
      cells responsible for producing the fibrosis of alcoholic chronic pancreatitis.
      Efforts to identify clinically relevant factors that may explain the
      susceptibility of some alcoholics to pancreatitis have been underway for several
      years. An unequivocal, functionally characterized, association is yet to be
      identified in clinical studies, although in the experimental setting, endotoxin
      has been shown to trigger overt pancreatic injury and to promote disease
      progression in alcohol-fed animals. Thus, while the molecular effects of alcohol
      on the pancreas have been increasingly clarified in recent years, identification
      of predisposing or triggering factors remains a challenge.

PMID- 21091992
TI  - Role of probiotics in management of diverticular disease.
AB  - Patients with diverticular disease may experience a variety of chronic symptoms,
      including abdominal discomfort, bloating, and altered bowel habit. They are also
      at risk of complications, including hemorrhage, diverticulitis, abscess, and
      fistula formation. The potential role of abnormal colonic microflora in the
      pathogenesis of diverticular inflammation has led to investigation of novel
      therapies such as probiotics. Probiotics are microorganisms that may be of net
      benefit to humans when consumed. The rationale and safety of their use in
      diverticular disease is discussed and current literature is reviewed.

PMID- 21091993
TI  - Clinical clues to suspicion of IgG4-associated sclerosing cholangitis disguised
      as primary sclerosing cholangitis or hilar cholangiocarcinoma.
AB  - BACKGROUND AND AIM: This study aimed to determine the clinical characteristics of
      immunoglobulin G4 (IgG4)-associated sclerosing cholangitis (ISC) and provide
      clinical clues differentiating ISC from primary sclerosing cholangitis (PSC) or
      hilar cholangiocarcinoma (CCC). METHODS: Sixteen patients with ISC manifesting as
      hilar/intrahepatic strictures were analyzed for clinical characteristics and
      compared with patients with PSC and hilar CCC as disease controls for histology
      and serum IgG4 levels. RESULTS: Distinguished biliary imaging findings of ISC
      included multifocal biliary tree involvement (n = 14), concentric bile duct
      thickening with preserved luminal patency (n = 13), and relatively mild proximal
      dilatation, despite prominent bile duct thickening (n = 11). Serum IgG4 levels
      were elevated in 12 patients (75%), but not in any of the 25 patients with hilar
      CCC. Ten patients (63%) had a past or concurrent history of autoimmune
      pancreatitis (AIP). The significant infiltration of IgG4-positive cells was
      observed with endobiliary or liver biopsy in 11 of 16 patients (69%) with ISC,
      but not in any patients with PSC or hilar CCC. Extrabiliary organ involvement,
      including sialadenitis, inflammatory pseudotumor of the liver and kidney, and
      retroperitoneal fibrosis, was present in seven patients. Marked improvement of
      biliary strictures and/or extrabiliary involvement was observed in all ISC
      patients after steroid therapy. CONCLUSIONS: ISC should be considered in the
      differential diagnosis of hilar/intrahepatic biliary strictures. Past or
      concurrent AIP or extrabiliary organ involvement strongly suggests the
      possibility of ISC. Significant infiltration of IgG4-positive cells on
      endobiliary or liver biopsy specimens, and/or elevated serum IgG4 levels, highly
      support the diagnosis of ISC and provide the rationale for steroid therapy.

PMID- 21091994
TI  - Progesterone inhibits L-type calcium currents in gallbladder smooth muscle cells.
AB  - BACKGROUND AND AIM: The incidence of gallbladder stones is higher in women during
      pregnancy than in men. Progesterone can inhibit gallbladder motility and
      facilitate gallstone formation. However, the ionic mechanisms have not been fully
      illuminated. This study sought to investigate the effects of progesterone on L
      type calcium currents and voltage-dependent potassium currents in gallbladder
      smooth muscle cells. METHODS: Gallbladder smooth muscle cells were isolated by
      enzymatic digestion from adult guinea pigs. Ionic currents were recorded by the
      whole-cell patch clamp method. RESULTS: Progesterone inhibited L-type calcium
      currents in a concentration-dependent manner. The characteristic of current
      voltage curve was not significantly altered. The amplitude of calcium currents
      was gradually suppressed, reached a steady-state level within 4-6 min, and
      restored partly after washout. In the presence of protein kinase A (PKA)
      inhibitor, Rp-cAMP, the inhibitory effect induced by progesterone was apparently
      attenuated, whereas forskolin, a direct activator of adenylate cyclase, could
      suppress L-type calcium channel. However, progesterone did not significantly
      affect voltage-dependent potassium currents. CONCLUSIONS: Progesterone inhibits L
      type calcium channel by cAMP/PKA pathway in gallbladder smooth muscle cells. This
      may be an important mechanism for the gallbladder hypomotility induced by
      progesterone.

PMID- 21091995
TI  - Autofluorescence imaging for predicting development of metachronous gastric
      cancer after Helicobacter pylori eradication.
AB  - BACKGROUND AND AIMS: Although Helicobacter pylori eradication decreases the
      incidence of metachronous gastric cancer after endoscopic treatment for early
      gastric cancer (EGC), metachronous cancer still develops after successful
      eradication, particularly in patients with severe corpus gastritis. We
      investigated whether the extent of atrophic fundic gastritis diagnosed by
      autofluorescence imaging (AFI) videoendoscopy is predictive of development of
      metachronous gastric cancer after H. pylori eradication in patients treated with
      endoscopic submucosal dissection (ESD) for EGC. PATIENTS AND METHODS: A total of
      82 patients who underwent ESD for EGC from 2003 to 2006, who received eradication
      therapy participated in this study. The extent of chronic atrophic fundic
      gastritis was evaluated by AFI and categorized into closed and open type. The
      main outcome was the incidence of metachronous gastric cancer detected by annual
      surveillance endoscopy. RESULTS: During a median observation period of 55 months,
      metachronous gastric cancer developed in 12 of 82 patients (14.6%). Multivariate
      Cox's proportional hazard analysis revealed that open-type, atrophic fundic
      gastritis diagnosed by AFI was significantly associated with development of
      metachronous gastric cancer (hazard ratio: 4.88, 95% confidence interval [CI]:
      1.32-18.2, P = 0.018) after adjustment for age, sex, histological intestinal
      metaplasia, serum pepsinogen level, and H. pylori status. CONCLUSIONS:
      Metachronous EGC developed after successful H. pylori eradication, and extensive
      atrophic fundic gastritis diagnosed by AFI was a significant predictor, thus it
      could identify patients undergoing ESD for EGC who still required intensive
      surveillance after eradication.

PMID- 21091996
TI  - Clinical results of observation of the upper gastrointestinal tract by
      transgastrostomic endoscopy using an ultrathin endoscope.
AB  - BACKGROUND AND AIM: Esophagogastroduodenoscopy through the oral cavity of
      patients who have undergone percutaneous endoscopic gastrostomy (PEG) causes some
      distress and puts these patients at risk of aspiration pneumonia. The aim of this
      study was to evaluate results for the upper gastrointestinal tract by
      transgastrostomic endoscopy using an ultrathin endoscope. METHODS: The study
      subjects were 43 patients, who underwent exchange of a PEG button or tube, 20
      French or more in diameter. After PEG buttons or tubes were extracted from the
      gastrostomy tract, an ultrathin endoscope was inserted through the gastrostomy
      tract. The stomach and the duodenal bulb were observed and the esophagus was
      observed in retrograde passage. A new PEG button or tube was then inserted. The
      rate of successful insertion into the esophagus and duodenal bulb, the
      observation of the gastrostomy site in retroversion in the stomach, and the
      endoscopic findings were analyzed. RESULTS: Ninety-nine examinations were carried
      out. The esophagus could be observed in 95 (96.0%), the duodenum in 92 (92.9%)
      and the gastrostomy site in the stomach in all. Gastric polyps were detected in
      four patients, gastric erosions in two, reflux esophagitis in two, polypoid
      lesion at the gastrostomy tract in two, gastric ulcer scar in one, duodenal ulcer
      scar in one, early gastric cancer in one and recurrent esophageal cancer in one.
      Neither discomfort nor complications occurred during transgastrostomic endoscopy.
      CONCLUSIONS: Observation of the upper gastrointestinal tract by transgastrostomic
      endoscopy using an ultrathin endoscope during a gastrostomy button or tube
      replacement may be useful and safe.

PMID- 21091997
TI  - Pathological bolus exposure plays a significant role in eliciting non-cardiac
      chest pain.
AB  - BACKGROUND AND AIM: Pathological bolus exposure is defined in the present study
      as cases in which all reflux percentage times are above 1.4% of the total reflux
      number, as revealed by impedance-pH monitoring. The role of pathological bolus
      exposure in the pathogenesis of non-cardiac chest pain (NCCP) is poorly known. We
      aimed to classify and characterize NCCP using combined impedance-pH monitoring.
      METHODS: Seventy-five consecutive patients with NCCP were prospectively enrolled
      from January 2006 to October 2008. All the patients underwent upper endoscopy,
      esophageal manometry, and 24-h multichannel intraluminal impedance (MII)-pH
      metering. RESULTS: Sixteen patients (21.3%) had esophageal erosion upon
      endoscopy. Upon esophageal manometry, 37 patients (49.3%) had esophageal
      dysmotility. When the patients were classified based on MII-pH metering, 16
      (21.3%) showed pathological acid exposure, and 40 (53.3%) showed pathological
      bolus exposure. The DeMeester score of patients with pathological acid exposure
      was higher than that of patients with pathological bolus exposure (P = 0.002).
      There was no significant difference in age, sex, typical esophageal symptoms,
      presence of esophageal erosion, esophageal dysmotility, improvement with proton
      pump inhibitor medication, symptom index >= 50%, percentage of time clearance pH
      below 4 >= 4%, and all reflux time >= 1.4% in the fasting period between the two
      groups. When the patients were divided into gastroesophageal reflux disease
      (GERD)-related NCCP and non-GERD-related NCCP groups based on MII-pH metering and
      upper endoscopy, there was no difference between the two groups. CONCLUSIONS:
      Combined impedance-pH monitoring improves the detection and characterization of
      NCCP. This study suggests that pathological bolus exposure plays a major role in
      eliciting NCCP.

PMID- 21091998
TI  - Ginger extract and polaprezinc exert gastroprotective actions by anti-oxidant and
      growth factor modulating effects in rats.
AB  - BACKGROUND AND AIM: Contemporary medications used in the treatment of gastric
      ulcers involve the use of novel mucosal protective drugs. The present study aimed
      to investigate the gastroprotective effect of ginger extract and polaprezinc in a
      rat model of acetic acid-induced gastric ulcer. METHODS: 'Kissing' ulcers were
      induced in male Sprague-Dawley rats by using 60% acetic acid. Rhizoma Zingiber
      officinale (ginger) extract (1.5-5 g/kg) or polaprezinc (30 and 60 mg/kg) was
      orally given to the animals once daily for three consecutive days after ulcer
      induction. All animals were killed on day 5 by an overdose of ketamine. RESULTS:
      Both ginger extract and polaprezinc significantly reduce the gastric ulcer area
      in a dose-dependent manner, with concomitant attenuation of the elevated
      activities of xanthine oxidase and myeloperoxidase, as well as malondialdehyde
      level in the ulcerated mucosa. Nevertheless, only polaprezinc could restore the
      mucosal glutathione level. Polaprezinc also causes the overexpression of basic
      fibroblast growth factor, vascular endothelial growth factor and ornithine
      decarboxylase, whereas ginger extract only increases the expression of the two
      growth factors in the gastric mucosa. Furthermore, polaprezinc could consistently
      downregulate the protein expression of tumor necrosis factor (TNF)-alpha,
      interleukin-1beta, macrophage inflammatory protein-2 and cytokine-induced
      neutrophil chemoattractant-2alpha that have been activated in the ulcerated
      tissues, whereas ginger extract mainly inhibits the expression of the chemokines
      and to some extent TNF-alpha. CONCLUSION: Ginger extract and polaprezinc both
      show anti-oxidation that consequently alleviates gastric mucosal damage and
      promotes ulcer healing, which together serve as effective mucosal protective
      agents.

PMID- 21091999
TI  - Tumor necrosis factor-alpha-secreting CD16+ antigen presenting cells are
      effectively removed by granulocytapheresis in ulcerative colitis patients.
AB  - BACKGROUND AND AIM: In human blood, two main subsets of antigen-presenting-cells
      (APCs) have been described: plasmocytoid dendritic cells (pDC) and myeloid
      dendritic cells (mDC) which are further subdivided in CD11c-mDC and CD16-mDC DC.
      In ulcerative colitis patients (UC) peripheral blood APCs express significant
      levels of the activation and lack immature-tolerogeneic APCs. Adacolumn selective
      granulocytapheresis (GCAP) has been associated with clinical efficacy in patients
      with UC. In the present study we sought the effect of sequential GCAP procedures
      in peripheral blood APCs in patients with UC and the effect on soluble cytokines.
      METHODS: We used multiparametric flow cytometry to quantify peripheral blood APCs
      and serum cytokines in 210 samples obtained from seven patients with steroid
      dependent or steroid resistant UC undergoing GCAP treatment. Samples were drawn
      before, after 30 and 60 min of each session. RESULTS: Each GCAP session resulted
      in a dramatic tenfold reduction of peripheral blood CD16-mDC (P < 0.01), pDC
      decreased twofold (P = 0.05) but CD11c-mDC remained unchanged. This depletion was
      reached after 30 min and maintained at 60 min. The depletion of CD16-mDC and
      monocytes was associated with a reduction of serum tumor necrosis factor levels
      and a raise in interleukin-10 levels, although no statistical difference was
      reached. CONCLUSION: The effect of GCAP in peripheral blood APC consisted mainly
      on a significant depletion of tumor necrosis factor-alpha secreting CD16-mDC.
      This finding could suggest a potential mechanism of GCAP beneficial effect that
      must be confirmed in larger series.

PMID- 21092000
TI  - Sustained low hepatitis B viral load predicts good outcome after curative
      resection in patients with hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Little is known about the role of hepatitis B virus (HBV)
      factors in the long-term prognosis of hepatocellular carcinoma (HCC) after
      resection. The objective of the present study was to identify the changing
      patterns of HBV levels and its effect on outcome after resection. METHODS: This
      study recruited 188 patients with HBV-related HCC who underwent curative
      resection. Among the 188 patients, 115 were alive without recurrence at 12
      months, and had serial measurements of viral levels. RESULTS: The mean age was 53
      years and the mean follow-up period was 48.5 months. With multivariate analysis,
      tumor size > 5 cm (P = 0.047), Child-Pugh class B (P = 0.017), vascular invasion
      (P = 0.028), and HBV DNA > 10(4) copies/mL at the time of resection (P = 0.003)
      were independently predictive of HCC recurrence for the entire population. For
      the 115 patients with serial measurements of viral levels, tumor size > 5 cm, HBV
      DNA > 10(4) copies/mL at resection, and the absence of sustained HBV DNA level <
      10(4) copies/mL, the presence of cirrhosis, and elevated aminotransferase levels
      (> 40 IU/L) were marginally or significantly associated with HCC recurrence and
      overall survival. However, on multivariate analysis, sustained HBV DNA level <
      10(4) copies/mL was the only factor for both low recurrence (P = 0.002; odds
      ratio [OR] 3.13; 95% confidence interval [CI] 1.55-6.35) and longer survival (P =
      0.002; OR 3.76; 95% CI 1.61-8.78). CONCLUSIONS: A high HBV replication state is
      among the most important predictors of adverse outcome after resection of HBV
      related HCC. The sustained suppression of HBV below 10(4) copies/mL is a strong
      protective factor for long-term recurrence-free and overall survival.

PMID- 21092001
TI  - Interferon-alpha suppressed granulocyte colony stimulating factor production is
      reversed by CL097, a TLR7/8 agonist.
AB  - BACKGROUND AND AIM: Neutropenia, a major side-effect of interferon-alpha (IFN
      alpha) therapy can be effectively treated by the recombinant form of granulocyte
      colony stimulating factor (G-CSF), an important growth factor for neutrophils. We
      hypothesized that IFN-alpha might suppress G-CSF production by peripheral blood
      mononuclear cells (PBMCs), contributing to the development of neutropenia, and
      that a toll-like receptor (TLR) agonist might overcome this suppression. METHODS:
      Fifty-five patients who were receiving IFN-alpha/ribavirin combination therapy
      for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil
      counts (ANC), monocyte counts and treatment outcome data were recorded. G-CSF
      levels in the supernatants of PBMCs isolated from the patients and healthy
      controls were assessed by enzyme-linked immunosorbent assay following 18 h of
      culture in the absence or presence of IFN- alpha or the TLR7/8 agonist, CL097.
      RESULTS: Therapeutic IFN-alpha caused a significant reduction in neutrophil
      counts in all patients, with 15 patients requiring therapeutic G-CSF. The
      reduction in ANC over the course of IFN-alpha treatment was paralleled by a
      decrease in the ability of PBMCs to produce G-CSF. In vitro G-CSF production by
      PBMCs was suppressed in the presence of IFN-alpha; however, co-incubation with a
      TLR7/8 agonist significantly enhanced G-CSF secretion by cells obtained both from
      HCV patients and healthy controls. CONCLUSIONS: Suppressed G-CSF production in
      the presence of IFN-alpha may contribute to IFN-alpha-induced neutropenia.
      However, a TLR7/8 agonist elicits G-CSF secretion even in the presence of IFN
      alpha, suggesting a possible therapeutic role for TLR agonists in treatment of
      IFN-alpha-induced neutropenia.

PMID- 21092003
TI  - Segmental meningomyelitis in 2 cats caused by Toxoplasma gondii.

PMID- 21092002
TI  - Attenuation of warm ischemia-reperfusion injury in the liver by bucillamine
      through decreased neutrophil activation and Bax/Bcl-2 modulation.
AB  - BACKGROUND AND AIM: Liver transplantation and resection surgery involve a period
      of ischemia and reperfusion to the liver, which initiates an inflammatory cascade
      resulting in liver and remote organ injury. Bucillamine is a low molecular weight
      thiol antioxidant that is capable of rapidly entering cells. We hypothesized that
      bucillamine acts by replenishing glutathione levels, thus reducing neutrophil
      activation, modulating Bax/Bcl-2 expression, and subsequently, attenuating the
      effects of warm ischemia-reperfusion injury (IRI) in the liver. METHODS: The
      effect of bucillamine was studied in a rat model of liver IRI with 45 min of
      partial (70%) liver ischemia and 3 h of reperfusion. Liver injury was assessed by
      measuring serum transaminases (aspartate aminotransferase [AST] and alanine
      aminotransferase [ALT]) and liver histology. Oxidative stress was quantified by
      measuring F(2) isoprostane and glutathione levels. Leukocyte adhesion was
      assessed by intravital microscopy, and inflammatory cytokine response was
      assessed by measuring serum cytokine-induced neutrophil chemoattractant-1 (CINC
      1) levels. Bax and Bcl-2 expression was measured by reverse transcription
      polymerase chain reaction. RESULTS: The model produced significant liver injury
      with elevated transaminases and an acute inflammatory response. Bucillamine
      reduced the liver injury, as indicated by reduced AST (932 +/- 200.8 vs 2072.5 +/
      511.79, P < 0.05). Bucillamine reduced Bax expression, serum CINC-1 levels, and
      neutrophil adhesion, and upregulated Bcl-2. However, bucillamine did not affect
      tissue glutathione levels nor the levels of oxidative stress, as measured by
      plasma and hepatic F(2) isoprostane levels. CONCLUSIONS: Bucillamine reduces warm
      ischemia-reperfusion in the liver by inhibiting neutrophil activation and
      modulating Bax/Bcl-2 expression.

PMID- 21092004
TI  - Insulin, glucagon, and leptin in critically ill foals.
AB  - BACKGROUND: Endocrine dysregulation of hormones of energy metabolism is well
      documented in critically ill humans, but limited information exists in septic
      foals. The purpose of this study was to provide information on the hormonal
      response to energy metabolism in critically ill foals, focusing on insulin,
      glucagon, and leptin. HYPOTHESIS: Concentrations of insulin, glucagon, leptin,
      and triglycerides will be higher, whereas glucose concentration will be lower in
      septic foals than in healthy and sick nonseptic foals. The magnitude of these
      differences will be associated with severity of disease and nonsurvival. ANIMALS:
      Forty-four septic, 62 sick nonseptic, and 19 healthy foals <7 days of age.
      METHODS: In this prospective multicenter cross-sectional study, blood samples
      were collected at admission. Foals with positive blood culture or sepsis score
      >=12 were considered septic. RESULTS: Septic foals had lower glucose and insulin
      and higher triglyceride and glucagon concentrations than did healthy foals.
      Glucagon concentrations were not different between septic foals that died (n =
      14) or survived (n = 30). Higher insulin and lower leptin concentrations were
      associated with mortality. Quantitative insulin-sensitivity check index was
      higher in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Energy metabolism
      and the endocrine response of related hormones in septic foals are characterized
      by hypoglycemia, hypertriglyceridemia, low insulin concentration, and high
      glucagon concentration. Leptin and insulin may have prognostic value for
      nonsurvival in septic foals. The hormonal response related to energy metabolism
      in critical illness differs between foals and humans.

PMID- 21092005
TI  - Transvenous coil embolization of patent ductus arteriosus in small (<=3.0 kg)
      dogs.
AB  - BACKGROUND: Surgical and interventional therapy for occlusion of a patent ductus
      arteriosus (PDA) in small dogs is challenging. Interventional closure of a PDA is
      rarely described in small dogs. HYPOTHESIS: Transvenous single-coil occlusion of
      a PDA in small (<=3.0 kg) dogs is possible and safe. ANIMALS: Twenty-one client
      owned dogs with a left-to-right shunting PDA. METHODS: Prospective clinical
      study. Inclusion criteria were a left-to-right shunting PDA and a body weight
      <=3.0 kg. Dogs with additional congenital cardiac diseases were excluded. Without
      arterial access, a single detachable coil was implanted by a transvenous approach
      with a 4 Fr catheter. RESULTS: Twenty-one dogs were the study population with
      Chihuahua and Yorkshire Terrier being the commonest breeds (n = 6 and n = 5,
      respectively). There were 14 female and 7 male dogs. The age range was 1.9-83.5
      months (median, 7.7 months), and the body weight was 1.0-2.9 kg (1.87 +/- 0.45).
      By angiography, the minimal ductal diameter measured 1.2-2.4 mm (median, 1.8 mm)
      and the PDA ampulla diameter was 2.4-5.9 mm (median, 4.6 mm). Coil implantation
      was successful in all dogs. After detachment of the coil from the delivery cable,
      repositioning of the pulmonary loop of the coil became necessary in 1 dog. The
      prevalence of immediate closure was 76%. The prevalence of cumulative closure was
      90%. CONCLUSION: For an experienced cardiologist, transvenous occlusion of a PDA
      in small dogs is possible with a 4 Fr catheter and a commercial single detachable
      coil. Arterial access is not essential. The procedure is safe and successful in
      experienced hands.

PMID- 21092006
TI  - Effects of zinc-L-carnosine and vitamin E on aspirin-induced gastroduodenal
      injury in dogs.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs frequently cause
      gastrointestinal (GI) injury. Zinc-L-carnosine has antioxidant, anti
      inflammatory, mucosal protective, and healing properties in rodent models and in
      some human studies of GI injury. HYPOTHESIS: The combination of zinc-L-carnosine
      and vitamin E attenuates aspirin-induced gastroduodenal mucosal injury. ANIMALS:
      Eighteen healthy random-source Foxhound dogs. METHODS: In this randomized, double
      blinded, placebo-controlled study dogs were treated with placebo (n = 6; 0X
      group), 30 mg/30 IU (n = 6; 1X group), or 60 mg/60 IU (n = 6; 2X group) zinc-L
      carnosine/vitamin E orally every 12 hours for 35 days. Between Day 7 and 35, GI
      mucosal lesions were induced with aspirin (25 mg/kg p.o. q8h). Mucosal injury
      lesions (hemorrhage, erosion, and ulcer) were assessed by gastroduodenoscopy on
      Days 14, 21, and 35 with a 12-point scoring scale. RESULTS: At baseline (Day -1)
      gastroscopy scores were not significantly different between groups (mean +/- SD:
      0X, 4.4 +/- 0.8; group 1X, 4.4 +/- 0.6; group 2X, 4.2 +/- 0.3; P= .55).
      Gastroscopy scores increased significantly in all groups between Day -1 and Days
      14, 21, and 35 (P < .0001). On Day 35, gastroscopy scores were 29.2 +/- 5.2 (0X),
      27.3 +/- 3.7 (1X), and 28.6 +/- 3.3 (2X). Mean gastroscopy scores were not
      significantly different among treatment groups on any of the days (P = .61).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of the combination of zinc-L
      carnosine and vitamin E at 1X or 2X dosing did not attenuate aspirin-induced
      gastroduodenal mucosal injury.

PMID- 21092007
TI  - Splenic marginal zone lymphoma in 5 dogs (2001-2008).
AB  - BACKGROUND: Splenic marginal zone lymphomas (MZL) in dogs arise from the marginal
      zone of B-cell follicles and can progress slowly. OBJECTIVES: To describe
      clinical features, treatment, and outcome of dogs with splenic MZL. ANIMALS: Five
      dogs with naturally occurring MZL. METHODS: Clinical, laboratory, and follow-up
      data were retrospectively reviewed. Diagnosis was based on clinical,
      histopathological, and immunophenotypic features. RESULTS: All dogs had stage IV
      disease; among them, 2 were symptomatic (substage "b") because of splenic
      rupture. Four dogs underwent splenectomy and adjuvant doxorubicin, and 1 dog
      underwent surgery only. Three out of the 4 dogs treated with surgery and
      chemotherapy died of causes unrelated to lymphoma, after 760, 939, and 1,825
      days, whereas the remaining dog was alive and in complete remission after 445
      days. The dog not receiving any adjuvant treatment had recurrence of the tumor
      after 180 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Splenic MZL appears indolent
      and can benefit from splenectomy, with or without systemic chemotherapy.

PMID- 21092008
TI  - Immunophenotype predicts survival time in dogs with chronic lymphocytic leukemia.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is a hematologic disorder in dogs,
      but studies on prognostic factors and clinical outcome are lacking. In people,
      several prognostic factors have been identified and currently are used to manage
      patients and determine therapy. OBJECTIVES: The aim of the study was to determine
      if the immunophenotype of neoplastic cells predicts survival in canine CLL.
      DESIGN: Retrospective study. ANIMALS: Forty-three dogs with CLL. PROCEDURES:
      Records of dogs with a final diagnosis of CLL were reviewed. For each included
      dog, a CBC, blood smear for microscopic reevaluation, and immunophenotyping data
      had to be available. Data on signalment, history, clinical findings, therapy,
      follow-up, as well as date and cause of death were retrieved. RESULTS: Seventeen
      dogs had B-CLL (CD21+), 19 had T-CLL (CD3+ CD8+), and 7 had atypical CLL (3 CD3-
      CD8+, 2 CD3+ CD4- CD8-, 1 CD3+ CD4+ CD8+, and 1 CD3+ CD21+). Among the variables
      considered, only immunophenotype was associated with survival. Dogs with T-CLL
      had approximately 3-fold and 19-fold higher probability of surviving than dogs
      with B-CLL and atypical CLL, respectively. Old dogs with B-CLL survived
      significantly longer than did young dogs, and anemic dogs with T-CLL survived a
      significantly shorter time than dogs without anemia. CONCLUSIONS: Although
      preliminary, results suggested that immunophenotype is useful to predict survival
      in dogs with CLL. Young age and anemia are associated with shorter survival in
      dogs with B-CLL and T-CLL, respectively.

PMID- 21092009
TI  - The effects of hypohydration on central venous pressure and splenic volume in
      adult horses.
AB  - BACKGROUND: Central venous pressure (CVP) is used in many species to monitor
      right-sided intravascular volume status, especially in critical care medicine.
      HYPOTHESIS: That hypohydration in adult horses is associated with a proportional
      reduction in CVP. ANIMALS: Ten healthy adult horses from the university teaching
      herd. METHODS: In this experimental study, horses underwent central venous
      catheter placement and CVP readings were obtained by water manometry. The horses
      were then deprived of water and administered furosemide (1 mg/kg IV q6h) for up
      to 36 hours. Weight, CVP, vital signs, PCV, total protein (TP), and serum lactate
      were monitored at baseline and every 6 hours until a target of 5% decrease in
      body weight loss was achieved. The spleen volume was estimated sonographically at
      baseline and peak volume depletion. Linear regression analysis was used to assess
      the association of CVP and other clinical parameters with degree of body weight
      loss over time. RESULTS: There was a significant association between CVP and
      decline in body weight (P < .001), with a decrease in CVP of 2.2 cmH(2)O for
      every percentage point decrease in body weight. Other significant associations
      between volume depletion and parameters measured included increased TP (P =
      .007), increased serum lactate concentration (P = .048), and decreased splenic
      volume (P = .046). There was no significant association between CVP and vital
      signs or PCV. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that
      CVP monitoring might be a useful addition to the clinical evaluation of hydration
      status in adult horses.

PMID- 21092010
TI  - Use of serum concentrations of interleukin-18 and monocyte chemoattractant
      protein-1 as prognostic indicators in primary immune-mediated hemolytic anemia in
      dogs.
AB  - BACKGROUND: The cytokine response in immune-mediated hemolytic anemia (IMHA) is
      poorly characterized and correlation with outcome is unknown.
      HYPOTHESIS/OBJECTIVES: To determine if cytokine activity is correlated with
      outcome in dogs with IMHA. ANIMALS: Twenty dogs with primary IMHA and 6 control
      dogs. METHODS: Prospective study on dogs with IMHA with blood sampling at
      admission. Serum activity of interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-8, IL-10,
      IL-15, IL-18, monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage
      colony stimulating factor (GM-CSF), interferon-inducible protein-10, interferon
      gamma, and keratinocyte chemoattractant (KC) was assessed. RESULTS: Thirty-day
      case fatality rate was 25% (5/20 dogs). Increased concentrations (median [range])
      of IL-2 (45.5 ng/L [0;830] versus 0 ng/L [0;46.8]), IL-10 (8.2 ng/L [0;60.6]
      versus 0 ng/L [0;88.2]), KC (1.7 MUg/L [0.3;4.7] versus 0.5 MUg/L [0.2;1.1]), and
      MCP-1 (162 ng/L [97.6;438] versus 124 ng/L [90.2;168]) were observed in dogs with
      IMHA compared with controls. The cytokine profile was indicative of a mixture of
      pro- and anti-inflammatory cytokines of various cellular origins.
      Cytokines/chemokines strongly associated with macrophage/monocyte activation and
      recruitment were significantly increased in nonsurvivors compared with survivors;
      IL-15 (179 ng/L [48.0;570] versus 21.3 ng/L [0;193]), IL-18 (199 ng/L [58.7;915]
      versus 37.4 ng/L [0;128]), GM-CSF (134 ng/L [70.0;863] versus 57.6 ng/L [0;164]),
      and MCP-1 (219 ng/L [135;438] versus 159 ng/L [97.6;274]), respectively. Logistic
      regression suggested increased IL-18 and MCP-1 concentrations were independently
      associated with mortality in this population (P<.05, Wald's type 3). CONCLUSIONS
      AND CLINICAL IMPORTANCE: A mixed cytokine response is present in dogs with IMHA
      and mediators of macrophage activation and recruitment might serve as prognostic
      indicators.

PMID- 21092011
TI  - Comparison of reduced intensity and myeloablative conditioning regimens for stem
      cell transplantation in patients with malignancies: a meta-analysis.
AB  - OBJECTIVE: The reduced intensity conditioning (RIC) stem cell transplantation is
      widely employed for the treatment of many hematologic malignancies, but the
      survival effectiveness is still unclear. This study conducted an updated meta
      analysis to determine whether any significant difference could be found by using
      RIC vs. myeloablative conditioning (MAC) regimen for transplantation in patients
      with malignancies. METHODS: We electronically searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and relevant articles
      (1987.01-2009.12). Comparative studies were carried out on clinical therapeutic
      effect of RIC and MAC on the survival outcomes and the transplantation-related
      complications. RESULTS: We obtained 1776 records, and 29 studies totaling 6235
      patients have been assessed. Compared with MAC regimen, the RIC regimen had a
      higher overall survival (OS) at one-yr and no difference at two-yr later after
      transplantation. RIC regimen had significantly lower rates of disease-free
      survival (DFS) after two-yr follow-up, lower incidences of >= II degree acute
      graft-versus-host disease (aGVHD), and lower TRM [OR, 0.61, 95% CI (0.53, 0.69)],
      but with a higher relapse rate [OR, 1.88(1.41, 2.51)]. No significant difference
      was found in rates of cytomegalovirus (CMV) infection and chronic GVHD between
      the regimens. CONCLUSIONS: This meta-analysis confirmed that compared with MAC
      condition regimen, the RIC regimen had a consistently equivalent or even better
      rate in OS, but with lower DFS at longer follow-up.

PMID- 21092012
TI  - Preanalytical stability of HIV-1 and HCV RNA: impact of storage and plasma
      separation from cells on blood donation testing by NAT.
AB  - BACKGROUND: The aim of this study was to evaluate the optimal preanalytical
      conditions prior to nucleic acid amplification technology (NAT) for human
      immunodeficiency virus-1 (HIV-1) or Hepatitis C virus (HCV) RNA in pools of 96
      plasma specimens with regard to storage temperature, time and plasma separation
      in a blood donation environment. STUDY DESIGN AND METHODS: Changes in viral
      nucleic acid concentration of HIV-1 and HCV were observed for 5 days according to
      the Paul-Ehrlich-Institute's (PEI) guidelines that demand 95%-detection limit of
      at least 10 000 IU mL(-1) for HIV-1 RNA and 5000 IU mL(-1) for HCV RNA within a
      single donor blood specimen. Ninety-five per cent detection limits of HIV-1 RNA
      over 3 days after storage at either 5 or 21  degrees C were evaluated by using
      standardised HIV-1 RNA-positive plasma. RESULTS: HCV RNA in whole blood samples
      proved to be more stable than HIV-1 RNA. Whole blood storage at 21  degrees C was
      shown to decrease the detectability of HIV-1 RNA even after only 18 h. Plasma
      samples once used for NAT at time 18 h did not alter viral stability up to 48 h
      after donation. Ninety-five per cent detection limits of HIV-1 RNA were securely
      below 10 000 IU mL(-1) for 24 h after whole blood storage at 5  degrees C.
      CONCLUSIONS: These results may lead to a discussion around the most suitable
      preanalytical conditions in blood donation environments. Contrary to the current
      PEI guidelines that allow storage of whole blood specimens up to 18 h at 21 
      degrees C, these results suggest that immediate storage in a 5  degrees C
      container after blood donation is more suitable and would permit storage of whole
      blood up to 24 h prior to the separation of plasma from cells.

PMID- 21092013
TI  - Functional characterisation of a complex mutation in the
      alpha(1,4)galactosyltransferase gene in Taiwanese individuals with p phenotype.
AB  - BACKGROUND AND OBJECTIVE: Individuals with p phenotype lack P1, P(k) and P
      antigens on red blood cells, presumably as a result of deficiency in the enzyme
      alpha(1,4)galactosyltransferase (A4GALT). The aim of this study was to explore
      the molecular background of a Taiwanese family with p phenotype. MATERIALS AND
      METHODS: Blood samples from two p siblings and seven family members were
      investigated. The coding region of the A4GALT gene was analysed by polymerase
      chain reaction and direct sequencing. The wild- and mutant-complementary DNAs
      (cDNAs) of A4GALT were cloned into an expression vector and transfected to
      Chinese hamster ovary (CHO) cells. P(k) expression on the transfected cells was
      analysed by flow cytometry and the activities of A4GALT were measured by high
      performance liquid chromatography. RESULTS: The two individuals with p phenotype
      were homozygous for the complex mutation, which was caused by a combined deletion
      and insertion between nt 418 and 428. No expression of P(k) and no enzyme
      activity were observed in cells transfected with the mutant construct.
      CONCLUSION: The first case of p phenotype in Taiwan was caused by a non
      functional allele resulting from a homozygous complex mutation of A4GALT gene.

PMID- 21092014
TI  - Future of nursing: Institute of Medicine report.

PMID- 21092015
TI  - Effect of telephone follow-up on adherence to a diabetes therapeutic regimen.
AB  - AIM: To determine whether a nurse telephone follow-up service could improve the
      level of adherence to a diabetes therapeutic regimen for patients with type 2
      diabetes. METHODS: A total of 61 patients attended a 3 day diabetes self-care
      program at the Iranian Diabetes Society. They were randomly assigned to one of
      the experimental or control groups. A telephone follow-up program was applied to
      the experimental group for 3 months, twice per week for the first month and
      weekly for the second and third months. The data-collection instruments included
      a data sheet to record the glycosylated hemoglobin (HbA1c) level and a
      questionnaire. The data were collected at baseline and after 12 weeks. RESULTS:
      There were significant differences between the control and the experimental
      groups in their adherence to a diabetic diet, exercise, foot care, blood glucose
      monitoring, and medication-taking. Also, the HbA1c levels differed significantly
      between the two groups after 3 months. CONCLUSION: A nurse-led telephone follow
      up was effective in enhancing the level of adherence to a diabetes therapeutic
      regimen, such that the HbA1c level decreased.

PMID- 21092016
TI  - Occupational exposure to blood and body fluids among a group of Turkish nursing
      and midwifery students during clinical practise training: frequency of
      needlestick and sharps injuries.
AB  - AIM: To ascertain the number of needlestick and sharps injuries (NSSIs) in
      nursing and midwifery students and to assess the use of universal precautions
      among injured and non-injured students. METHODS: A survey of a representative
      sample of nursing and midwifery students who did clinical practise in a hospital
      was conducted. In total, 203 students met the inclusion criterion of the study.
      Of these, 141 (69.46%) provided useable data. The survey form was designed by the
      researcher after reviewing the relevant literature. The data frequency,
      percentages, and chi(2) -values were examined. RESULTS: According to the data,
      35.5% of the participating students had experienced a NSSI, 54% of the students
      had received one NSSI, and 36.0% had two NSSIs. Sixty-six percent of the injured
      students had been injured by an ampoule and the majority of injuries occurred in
      the treatment room. Most of the students had washed their injury with antiseptic
      solution and 84% had not told anyone about their injury. While 86.5% of the
      students threw away used needles in the special sharps containers disposal box,
      89.4% also stated that they always recapped used needles. Almost all the students
      had received the hepatitis B vaccine. Only 14% of the students stated that they
      always wore gloves. CONCLUSIONS: This study shows that a significant percentage
      of nursing and midwifery students receive NSSIs. It is very important to
      frequently review information about preventive measures so that the students
      practise them during clinical practise every semester. Moreover, the instructors
      should monitor if the students are taking the necessary preventive measures
      without fail.

PMID- 21092017
TI  - Psychometric properties of the Caregiving Burden Scale for Family Caregivers with
      Relatives in Nursing Homes: scale development.
AB  - AIM: Most family caregivers continue their caregiving for frail relatives after
      admitting them to long-term care facilities. The characteristics of this
      caregiving differ from those related to caregiving in home-care settings. Thus, a
      new tool to evaluate the burden of family caregivers in institutional settings is
      needed. The aim of this study was to develop a new scale, the Caregiving Burden
      Scale for Family Caregivers with Relatives in Nursing Homes, and to confirm its
      validity and reliability. METHODS: We conducted two cross-sectional questionnaire
      surveys. The participants were a convenience sample of family members of
      residents in seven nursing homes for the validation study and in three nursing
      homes for the test-retest study in Japan. Statistical analyses examined
      exploratory/confirmatory factor analyses, internal consistency,
      concurrent/discriminate validity, and test-retest reliability. RESULTS: A four
      factor solution with 16 items was selected as the most interpretable
      questionnaire. In the confirmatory factor analysis, the indices of fitness highly
      supported these results. The Cronbach's alpha coefficient for the total score was
      0.86 and varied between 0.77 and 0.87 in the four domains. The scale showed
      moderate correlation with the Nursing Home Hassles Scale, suggesting its
      concurrent validity. The four domains had only a medium correlation with each
      other, indicating discriminate validity. CONCLUSIONS: The developed scale has
      acceptable validity and reliability for measuring the caregiving burden of family
      members with relatives in Japanese nursing homes. Future studies using the scale
      might lead to the improvement of care for family members with relatives in a long
      term care setting.

PMID- 21092018
TI  - Decision-making process of patients with gynecological cancer regarding their
      cancer treatment choices using the analytic hierarchy process.
AB  - AIM: In order to support patients' decision-making regarding cancer treatments,
      it is important to clarify which criteria that cancer patients use to set
      priorities in their treatment choices. Using the analytic hierarchy process
      (AHP), a mathematical decision-making method, this article investigates the
      criteria and the priorities of patients with gynecological cancer. METHODS: In
      the AHP, multiple and hierarchical criteria in the decision-making process were
      organized by a repeated pairwise judgment of the participants so as to serialize
      the alternatives along with the rational order of the priorities. For the
      alternatives "to receive treatment" and "to not receive treatment," the following
      five criteria were set: "anxiety about relapse and metastasis", "distress about
      side-effects", "advice of family", "advice of medical staff", and "economic
      burden". The participants determined a pairwise priority scale, as well as a
      priority scale between the alternatives for every criterion. The logical
      consistency of their answers was checked by a consistency index (CI). The
      participants were 31 patients with ovarian or endometrial cancer who were being
      followed up after undergoing surgery and adjuvant chemotherapy. RESULTS: Of the
      participants who answered the questionnaire, 17 satisfied the logical
      consistency. Of the five criteria for the treatment choices, "anxiety about
      relapse and metastasis" and "advice of medical staff" were found to be the
      important factors for treatment choice; however, the weight attached to the
      priority criteria differed much among the patients. CONCLUSION: The AHP made it
      possible to support patients' decision-making in order to clarify their priority
      criteria and to quantitatively present their decision-making process.

PMID- 21092019
TI  - Relationship between work-family conflict and a sense of coherence among Japanese
      registered nurses.
AB  - AIM: Work-family conflict (WFC) refers to the conflict that arises between a
      person's work and family life. Previous studies have reported workload, job
      demands, and irregular working shifts as related to the WFC among nurses and have
      clarified that WFC is a predictor of job satisfaction, morale, and turnover
      intention. Very few studies have investigated WFC among Japanese nurses and no
      study has taken into consideration the sense of coherence (SOC) that helps nurses
      to cope with stress. The present study aimed to determine the relationship
      between WFC and SOC and to clarify how WFC and a SOC influence the mental and
      physical health of nurses in order to suggest ways of establishing work
      environments that enable nurses to achieve a balance between their work and
      family life. METHODS: A self-report questionnaire survey of 388 Japanese female
      nurses was conducted. The data from 138 nurses who were a mother and/or wife were
      analyzed. RESULTS: Work-family conflict was significantly related to the SOC. It
      had a larger impact on the physical and mental health of nurses than their work
      and family characteristics. The SOC also had a major influence on the physical
      and mental health of nurses, while having a buffering effect on WFC with respect
      to depression. CONCLUSIONS: Our findings underscore the importance of taking
      organizational steps to create work environments that contribute to an enhanced
      SOC in order to reduce the WFC among nurses.

PMID- 21092020
TI  - Identification of a novel HLA-DRB1 allele, DRB1*11:95.
AB  - The DRB1*11:95 showed a single nucleotide difference with the DRB1*11:01:01
      allele at codon 10 (TAC/TGC).

PMID- 21092021
TI  - B*39:60, a novel HLA-B*39 allele identified by sequence-based typing.
AB  - The new allele B*39:60 showed one nucleotide difference with B*39:01:01 at codon
      152 (GTG/GCG).

PMID- 21092022
TI  - IDO1 and IDO2 gene expression analysis by quantitative polymerase chain reaction.
AB  - Immunomodulatory properties of IDO1 relate to tryptophan catabolism. The
      degradation of tryptophan by IDO1 leads to suppression of T cell responses.
      Recently, another enzyme with IDO-like activity, indoleamine 2,3-dioxygenase-like
      protein 1 (INDOL1, IDO2), has been described in both mice and humans. In order to
      study the gene expression of IDO1 and IDO2, we have developed a quantitative PCR
      (qPCR) assay. In an exploratory application to the study of the differential
      expression of IDO1 and IDO2 by professional antigen-presenting cells and MSCs
      (mesenchymal stromal cells) under the influence of interferon-gamma (IFN-gamma)
      and T-lymphocyte conditioned media (TCM), substantial differences were observed.
      IDO expression measured by qPCR was valid and reliable in the cell types
      investigated. Further studies are needed to delineate factors driving IDO
      expression in MSCs.

PMID- 21092023
TI  - Meta-analytic review of neurocognition in bipolar II disorder.
AB  - OBJECTIVE: The clinical distinction between bipolar II disorder (BD II) and
      bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the
      potential to explore objective markers to help delineate this boundary. To
      examine this issue, we conducted a quantitative review of the cognitive profile
      of clinically stable patients with BD II in comparison with both patients with BD
      I and healthy controls. METHOD: Meta-analytical methods were used to compare
      cognitive functioning of BD II disorder with both BD I disorder and healthy
      controls. RESULTS: Individuals with BD II were less impaired than those with BD I
      on verbal memory. There were also small but significant difference in visual
      memory and semantic fluency. There were no significant differences in global
      cognition or in other cognitive domains. Patients with BD II performed poorer
      than controls in all cognitive domains. CONCLUSION: Our findings suggest that
      with the exception of memory and semantic fluency, cognitive impairment in BD II
      is as severe as in BD I. Further studies are needed to investigate whether more
      severe deficits in BD I are related to neurotoxic effects of severe manic
      episodes on medial temporal structures or neurobiological differences from the
      onset of the illness.

PMID- 21092024
TI  - A comprehensive meta-analysis of the risk of suicide in eating disorders.
AB  - OBJECTIVE: Past meta-analyses on suicide in eating disorders included few
      available studies. METHOD: PubMed/Medline search for papers including sample n
      >=40 and follow-up >=5 years: 40 studies on anorexia nervosa (AN), 16 studies on
      bulimia nervosa (BN), and three studies on binge eating disorder (BED) were
      included. RESULTS: Of 16,342 patients with AN, 245 suicides occurred over a mean
      follow-up of 11.1 years (suicide rate=0.124 per 100 person-years). Standardized
      mortality ratio (SMR) was 31.0 (Poisson 95% CI=21.0-44.0); a clear decrease in
      suicide risk over time was observed in recent decades. Of 1768 patients with BN,
      four suicides occurred over a mean follow-up of 7.5 years (suicide rate=0.030 per
      100 person-years): SMR was 7.5 (1.6-11.6). No suicide occurred among 246 patients
      with BED (mean follow-up=5.3 years). CONCLUSION: AN and BN share many risk
      factors for suicide: the factors causing lower suicide rates per person-year in
      BN compared to AN should be investigated.

PMID- 21092025
TI  - Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases
      of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%.
AB  - The safety and efficacy of rituximab with CODOX-M/IVAC (cyclophosphamide,
      doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose
      cytarabine) was retrospectively analysed in 23 patients with non-human
      immunodeficiency virus-related B-cell non-Hodgkin lymphoma with proliferation
      index >95% [14 with classical Burkitt lymphoma (BL), five with B-cell lymphoma
      unclassifiable, with features intermediate between diffuse large B cell lymphoma
      (DLBCL) and BL, and four with DLBCL]. Six (26%) low-risk (LR) patients received
      three cycles of CODOX-M and 17 (74%) high-risk (HR) cases were assigned to four
      cycles of alternating CODOX-M/IVAC. Rituximab 375 mg/m2 was infused on days 1 and
      10 of each cycle. Toxicity was comparable to that reported with CODOX-M/IVAC,
      with no treatment-related death. Two patients developed grade 3 rituximab-induced
      delayed neutropenia, with no adverse outcome. After completing treatment, 83% LR
      patients and 71% HR patients achieved CR by positron emission tomography
      computerized tomography (PET-CT). Three (13%) patients received salvage
      treatment. At a median follow-up of 34 months (range = 18-75), 19 (83%) patients
      (100% LR and 74% HR) were alive, including one case undergoing salvage for late
      relapse. Four HR patients (17%) had died, three from primary progressive disease
      and one from treatment-refractory relapse 2 months after achieving CR. These
      results with R-CODOX-M/R-IVAC compare favourably with existing data using CODOX
      M/IVAC and warrant further prospective studies. The potential pitfalls of PET-CT
      to assess response are highlighted.

PMID- 21092026
TI  - Migraine and hypercoagulability, are they related? A clinical study of
      thrombophilia in children with migraine.

PMID- 21092027
TI  - Outcomes of the Sixth International Conference on Pediatric Mechanical
      Circulatory Support systems and Pediatric Cardiopulmonary Perfusion and First
      Annual Meeting of the International Society for Pediatric Mechanical
      Cardiopulmonary Support.

PMID- 21092028
TI  - Evolution of the extracorporeal life support circuitry.

PMID- 21092029
TI  - Pulsatile flow improves cerebral blood flow in pediatric cardiopulmonary bypass.
AB  - The objective of this study was to evaluate the effect of pulsatile flow on
      cerebral blood flow (CBF) in infants with the use of a mild hypothermic
      cardiopulmonary bypass (CPB). Thirty infants scheduled for open heart surgery
      were randomized to the pulsatile group (Group P, n = 15) and nonpulsatile group
      (Group NP, n = 15). In Group P, pulsatile perfusion was applied during the aortic
      cross-clamping period, whereas nonpulsatile perfusion was used in Group NP. The
      systolic peak velocity (Vs), the end of diastolic velocity (Vd), the mean
      velocity (Vm), and the pulsatility index (PI) and the resistance index (RI) of
      the middle cerebral artery were measured by a transcranial Doppler (TCD)
      ultrasound after anesthesia (T1; baseline), at the beginning of CPB (T2), 10 min
      after aortic cross-clamping (T3), 3 min after declamping (T4), at the cessation
      of CPB (T5), and at the end of the operation (T6). During T3 and T4, the Vs in
      Group P was significantly higher than in Group NP. However, there were no
      statistically significant differences between Vd and Vm. The PI and RI in Group P
      were also higher than those in Group NP (both P < 0.05). During T5, Vd and Vm
      were higher in Group P (P < 0.05), whereas there was no difference in Vs.
      Additionally, PI and RI in Group P were significantly lower than those in Group
      NP (P < 0.05). However, there was no difference during T6. Pulsatile perfusion
      may increase CBF and decrease cerebral vascular resistance in the early period
      after mild hypothermic CPB.

PMID- 21092030
TI  - Evaluation of perfusion modes on vital organ recovery and thyroid hormone
      homeostasis in pediatric patients undergoing cardiopulmonary bypass.
AB  - The objectives of this study were: (i) to evaluate the effects of perfusion modes
      (pulsatile vs. nonpulsatile) on vital organs recovery and (ii) to investigate the
      influences of two different perfusion modes on the homeostasis of thyroid
      hormones in pediatric patients undergoing cardiopulmonary bypass (CPB)
      procedures. Two hundred and eighty-nine consecutive pediatric patients undergoing
      open heart surgery for repair of congenital heart disease were prospectively
      entered into the study and were randomly assigned to two groups: the pulsatile
      perfusion group (Group P, n = 208) and the nonpulsatile perfusion group (Group
      NP, n = 81). All patients received identical surgical, perfusional, and
      postoperative care. Study parameters included total drainage, mean urine output
      in the intensive care unit (ICU), intubation time, duration of ICU and hospital
      stay, the need for inotropic support, pre- and postoperative enzyme levels (ALT
      [alanine aminotransaminase] and AST [aspartate aminotransaminase]), c-reactive
      protein, lactate, albumin, blood count (leukocytes, hematocrit, platelets),
      creatinine levels, and thyroid hormones (thyroid stimulating hormone [TSH], FT(3)
      [free triiodothyronine], FT(4) [free thyroxine]). All patients survived the
      perioperative and postoperative periods. There were no statistically significant
      differences in either preoperative or operative parameters between the two
      groups. Group P, compared to Group NP, required significantly less inotropic
      support, had a shorter intubation period, higher urine output in ICU, and shorter
      duration of ICU and hospital stay. Lower lactate levels and higher albumin levels
      were observed in Group P and there were no significant differences in creatinine,
      enzyme levels, blood counts, or drainage amounts between two groups. TSH, Total
      T(3) , Total T(4) , and FT(3) , FT(4) levels were markedly reduced versus their
      preoperative values in both groups. FT(3) and FT(4) levels were reduced
      significantly further in the nonpulsatile group both during CPB and at 72 h
      postoperation. The results of this study confirm our opinion that pulsatile
      perfusion leads to better vital organ recovery and clinical outcomes in the early
      postoperative period as compared to nonpulsatile perfusion in pediatric patients
      undergoing CPB cardiac surgery. The plasma concentrations of thyroid hormones are
      dramatically reduced during and after CPB, but pulsatile perfusion seems to have
      a protective effect of thyroid hormone homeostasis compared to nonpulsatile
      perfusion.

PMID- 21092031
TI  - Cardiac surgery of premature and low birthweight newborns: is a change of fate
      possible?
AB  - Low birthweight (LBW) continues to be a high-risk factor in surgery for
      congenital heart disease. This risk is particularly very high in very low
      birthweight infants under 1500g and extremely LBW infants under 1000g. From
      January 2005 to December 2008, 33 consecutive LBW neonates underwent cardiac
      surgery in our clinic in keeping with the criteria for choice of surgery. Their
      weight range was between 800 and 1900g. Nine of them were under 1000g.
      Cardiopulmonary bypass (CPB) was used in 17 patients (39.5%) and pulsatile
      perfusion mode was applied to patients in the CPB group. The same surgical team
      operated to achieve palliation (8 patients, 24.2%) or full repair (25 patients,
      75.8%). Median gestational age was 36 weeks with 12 (36.4%) premature babies
      (<=37 weeks). Median age at operation was 5 days. Pathologies were single
      ventricle (n=3), pulmonary atresia-ventricular septal defect (n=3), aortic
      coarctation (n=10), aorticopulmonary window and interrupted aortic arch
      combination (n=6), patent arterial duct (n=11), critical aortic stenosis (n=8),
      and tetralogy of Fallot with pulmonary atresia (n=2). One infant had VATER
      syndrome. Selective cerebral perfusion technique was used in complex arch
      pathologies for cerebral protection. Median follow-up was 14 months. There were
      four early postoperative deaths. None of the cases showed a need for early
      reoperation. The acceptable early- and midterm mortality rates in this group
      suggest that these operations can be successfully performed. There is a need for
      further multicenter studies to evaluate these high-risk groups.

PMID- 21092032
TI  - Extracorporeal membrane oxygenation following Norwood stage 1 procedures at a
      single institution.
AB  - Extracorporeal membrane oxygenation (ECMO) is an important circulatory assist for
      children with refractory cardiopulmonary dysfunction, but its role and
      indications after a stage 1 Norwood procedure are controversial. We assessed
      outcomes and risk factors in patients who underwent a Norwood palliation and ECMO
      at our institution. We retrospectively reviewed all patients who underwent a
      Norwood procedure and were supported with ECMO between January 1998 and January
      2010. Of the 91 children who underwent a Norwood procedure during the study
      period, there were 15 postoperative runs of ECMO in 12 patients. The diagnoses of
      the patients included five with hypoplastic left heart syndrome, five with a
      hypoplastic left heart syndrome variant, and two with critical aortic stenosis. A
      total of four patients underwent bilateral pulmonary artery banding, and two
      patients underwent aortic valvuloplasty before the stage 1 Norwood procedure. The
      mean age of the patients was 28+/-30 days, and mean body weight was 2.6+/-0.5kg
      at the induction of ECMO. The indications for ECMO were low cardiac output in six
      children, circulatory collapse needing cardiopulmonary resuscitation in six
      children, and hypoxemia in three children. Five of the 12 patients were
      successfully weaned from ECMO. The significant risk factors for the inability to
      be weaned from ECMO were a history of circulatory collapse requiring
      cardiopulmonary resuscitation, and the induction of ECMO in the intensive care
      unit. Induction of ECMO may be considered earlier when hemodynamics are unstable
      in impaired patients following a stage 1 Norwood procedure to avoid circulatory
      collapse.

PMID- 21092033
TI  - Description of a flow optimized oxygenator with integrated pulsatile pump.
AB  - Extracorporeal membrane oxygenation (ECMO) is a well-established therapy for
      several lung and heart diseases in the field of neonatal and pediatric medicine
      (e.g., acute respiratory distress syndrome, congenital heart failure,
      cardiomyopathy). Current ECMO systems are typically composed of an oxygenator and
      a separate nonpulsatile blood pump. An oxygenator with an integrated pulsatile
      blood pump for small infant ECMO was developed, and this novel concept was tested
      regarding functionality and gas exchange rate. Pulsating silicone tubes (STs)
      were driven by air pressure and placed inside the cylindrical fiber bundle of an
      oxygenator to be used as a pump module. The findings of this study confirm that
      pumping blood with STs is a viable option for the future. The maximum gas
      exchange rate for oxygen is 48mL/min/L(blood) at a medium blood flow rate of
      about 300mL/min. Future design steps were identified to optimize the flow field
      through the fiber bundle to achieve a higher gas exchange rate. First, the
      packing density of the hollow-fiber bundle was lower than commercial oxygenators
      due to the manual manufacturing. By increasing this packing density, the gas
      exchange rate would increase accordingly. Second, distribution plates for a more
      uniform blood flow can be placed at the inlet and outlet of the oxygenator.
      Third, the hollow-fiber membranes can be individually placed to ensure equal
      distances between the surrounding hollow fibers.

PMID- 21092034
TI  - A newly developed miniaturized heart-lung machine--expression of inflammation in
      a small animal model.
AB  - Cardiopulmonary bypass may cause severe inflammatory reactions and multiorgan
      failure, especially in premature and low-weight infants. This is due in part to
      the large area of contact with extrinsic surfaces and the essential addition of
      foreign blood. Thus, we developed a new miniaturized heart-lung machine (MiniHLM)
      with a total static priming volume of 102mL (including arterial and venous lines)
      and tested it in a small animal model. Seven Chinchilla Bastard rabbits were
      perfused with the MiniHLM (dynamic priming volume 127mL). Seven animals serving
      as a control were perfused using Dideco Kids and a Stockert roller pump (modified
      dynamic priming volume 149mL). The rabbits were anesthetized and sternotomized,
      followed by cannulation of the aorta and the right atrium. The aorta was clamped
      for 1h. Blood for examination of inflammation (TNF-alpha, IL-1beta, IL-6, IL-8,
      and IL-10) and blood gas analysis were taken before skin incision, 5min before
      opening of the aorta, 15min after opening of the aorta, and 4 h after the
      initiation of cardiopulmonary bypass. The parameters of inflammation were
      expressed by means of the comparative C(T) method (DeltaDeltaC(T) method). After
      gradual reduction of perfusion with the HLM, the heart was decannulated, and the
      sternum was closed. All rabbits were successfully weaned from cardiopulmonary
      bypass. Blood gas analysis was unremarkable in all cases. Foreign blood was not
      administered. Although statistical significance was not achieved, there was a
      reduced expression of inflammatory markers in the MiniHLM group. The newly
      developed MiniHLM prototype was tested successfully in a small animal model in
      terms of technical function and expression of inflammation. Upcoming tests with
      the industrially manufactured MiniHLM may reveal the advantages of the MiniHLM in
      comparison with the conventional HLM.

PMID- 21092035
TI  - Evaluation of neonatal membrane oxygenators with respect to gaseous microemboli
      capture and transmembrane pressure gradients.
AB  - A series of studies performed at our center demonstrates that gaseous microemboli
      (GME) remain a challenge in cardiac surgical procedures. Evaluation of novel
      oxygenators must address hemodynamic parameters and microemboli capture
      capability. The objective of this study is to compare two neonatal membrane
      oxygenators, the Quadrox-i (MAQUET Cardiopulmonary AG, Hirrlingen, Germany) and
      the Capiox RX05 (Terumo Corporation, Tokyo, Japan), with respect to GME capture
      and hemodynamic energy delivery. The experimental circuit included a Maquet HL-20
      heart-lung machine, a Heater-Cooler Unit HCU 30 (MAQUET Cardiopulmonary AG), a
      membrane oxygenator (Quadrox-i Neonatal or Capiox RX05), and 1/4-inch tubing from
      the COBE Heart/Lung Perfusion Pack (COBE Cardiovascular, Inc., Arvada, CO, USA).
      A Capiox cardiotomy reservoir CX*CR10NX (Terumo Corporation) acted as a
      pseudopatient. The circuit was primed with human packed red blood cells and
      lactated Ringer's solution and de-aired according to clinical priming procedure.
      Heparin (5000IU) was added into the circuit. The total volume was 400mL and
      hematocrit was 30%. Pump flow rate was maintained at 500 or 1000mL/min under both
      pulsatile and nonpulsatile modes. All trials were conducted under 100mm Hg of
      circuit pressure at normothermia (35 degrees C). In each trial, bolus air (0.5mL)
      was injected into the circuit at the prepump site over 5s. Total emboli counts
      and total emboli volume were significantly reduced by the Quadrox-i Neonatal
      membrane oxygenator compared to the Capiox RX05 membrane oxygenator.
      Classification and quantification of GME detected at the postoxygenator site at
      two different flow rates indicated that the Quadrox-i Neonatal captures the
      majority of microemboli larger than 40um in diameter. The Quadrox-i Neonatal
      membrane oxygenator had a higher transmembrane pressure drop at 500mL/min,
      whereas it had a lower pressure drop at 1000mL/min compared to the Capiox Baby
      RX05 oxygenator. Additionally, the Quadrox-i Neonatal oxygenator preserved more
      pulsatile energy than the Baby RX05 oxygenator at both flow rates. Compared to
      the Capiox RX05 membrane oxygenator, the Quadrox-i Neonatal membrane oxygenator
      has significantly improved GME handling capacity and had better hemodynamic
      energy preservation. Further research encompassing in vivo and clinical studies
      is needed to investigate the magnitude and mechanisms of these benefits.

PMID- 21092036
TI  - Improving oxygenator performance using computational simulation and flow field
      based parameters.
AB  - Current goals in the development of oxygenators are to reduce extrinsic surface
      contact area, thrombus formation, hemolysis, and priming volume. To achieve these
      goals and provide a favorable concentration gradient for the gas exchange
      throughout the fiber bundle, this study attempts to find an optimized inlet and
      outlet port geometry to guide the flow of a hexagonal-shaped oxygenator currently
      under development. Parameters derived from numerical flow simulations allowed an
      automated quantitative evaluation of geometry changes of flow distribution
      plates. This led to a practical assessment of the quality of the flow. The
      results were validated qualitatively by comparison to flow visualization results.
      Two parameters were investigated, the first based on the velocity distribution
      and the second calculated from the residence time of massless particles
      representing erythrocytes. Both approaches showed significant potential to
      improve the flow pattern in the fiber bundle, based on one of the parameters of
      up to 66%. Computational fluid dynamics combined with a parameterization proved
      to be a powerful tool to quickly improve oxygenator designs.

PMID- 21092037
TI  - Perioperative monitoring of thromboelastograph on blood protection and recovery
      for severely cyanotic patients undergoing complex cardiac surgery.
AB  - In this study, we assessed the clinical effect of a new transfusion therapy
      guided by thromboelastograph (TEG) on blood protection. Thirty-one children with
      severe cyanosis (hematocrit >=54%), who were diagnosed as having transposition of
      the great arteries or double outlet right ventricle with or without pulmonary
      valve stenosis, and underwent arterial switch operation or double roots
      transplantation, were involved and were divided into two groups. In group F
      (n=17), the transfusion therapy after cardiopulmonary bypass was performed with
      fibrinogen administration combined with traditional transfusion, guided by TEG.
      In group C (n=14), traditional transfusion guided by clinical experiences only
      was performed. We observed the blood protection effects and recovery conditions
      of these patients. In surgery, compared with group C, the chest closure time,
      fresh-frozen plasma (FFP), and platelet (PLT) volume used at closure time had no
      significant reductions in group F (P>0.05, respectively), and the patients in
      group F had no significant reductions in the amount of chest drainage (P>0.05).
      The total PLT and total red blood cells usage were also the same (P>0.05). But
      during the first 24h, FFP usage in the intensive care unit (ICU) and total
      perioperative FFP usage had significantly dropped in group F (P<0.05); the
      mechanical ventilator time, ICU stay, and hospitalization time in group F were
      much shorter than those in group C (P<0.05). So, TEG was effective in
      perioperative blood protection. Fibrinogen could be a substitute for FFP to
      restore hemostasis and improve the prognosis for these patients.

PMID- 21092038
TI  - Relation between renal dysfunction requiring renal replacement therapy and
      promoter polymorphism of the erythropoietin gene in cardiac surgery.
AB  - Several genetic polymorphisms have been identified to play a role in the
      occurrence and progression of renal dysfunction after cardiac surgery with
      cardiopulmonary bypass (CPB). Recently, it was demonstrated that the T allele of
      SNP rs1617640 in the promoter of the erythropoetin (EPO) gene is significantly
      associated with proliferative diabetic retinopathy (PDR) and end-stage renal
      disease (ESRD) due to increased EPO expression. This disease risk-associated gene
      and its potential pathway mediating severe microvascular complications in T
      allele carriers could also play a role on renal dysfunction in patients who
      underwent cardiac surgery with CPB. We hypothesized that the patients' ability to
      produce increased EPO concentrations will affect morbidity and mortality after
      CPB. We conducted a prospective single center study between April 2006 and May
      2007. In 481 patients who underwent cardiac surgery with CPB we prospectively
      examined the SNP rs1617640 in the promoter of the EPO gene by DNA sequencing. The
      patients were grouped according to their genotype (GG, GT, and TT). The genotype
      distribution of SNP rs1617640 in the promoter of the EPO gene was 36% (TT), 49%
      (TG), and 15% (GG). There was no difference in age, body mass index, gender, CPB
      time, or length of stay in intensive care unit. The hospitalization was
      irrespective of the patients' genotypes. The baseline creatinine in the TT group
      was 0.2 points higher than in the other groups; however this was without
      statistical significance in the multivariate analysis. No significant difference
      was shown in Euroscore, the Simplified Acute Physiology Score II, the Acute
      Physiology and Chronic Health Evaluation Score II, Acute Renal Failure Score, or
      the Risk, Injury, Failure, Loss of Kidney Function Score. The mortality was equal
      across the genotypes. However, an association between the TT genotype and acute
      renal replacement therapy (P=0.03), intra-aortic balloon pump usage (P=0.02), and
      serum creatine phosphokinase-MB increase (P=0.03) were observed after cardiac
      surgery. Our analysis suggests that the risk allele (T) of rs1617640 plays a role
      in the development of renal dysfunction after cardiac surgery with CPB. Patients
      with the TT risk allele required more frequent acute renal replacement therapy.
      Since our result is close to the border of significance, this hypothesis should
      be investigated in larger prospective studies with long-term follow-up to
      emphasize this polymorphism as a potential risk factor.

PMID- 21092039
TI  - The role of phospho-adenosine monophosphate-activated protein kinase and vascular
      endothelial growth factor in a model of chronic heart failure.
AB  - We established a stable and reproducible animal model of chronic heart failure
      (CHF) in sheep to investigate biomolecular changes. Therefore, two biomarkers,
      adenosine monophosphate-activated protein kinase (AMPK) and vascular endothelial
      growth factor-A (VEGF-A) were examined to reveal their role during chronic
      ischemic conditions of the heart. AMPK was studied because it plays an important
      role in cellular energy homeostasis and its upregulation is associated with
      myocardial ischemia, whereas VEGF-A was studied because it acts as an important
      signaling protein for neoangiogenesis. We examined 15 juvenile sheep (mean
      weight, 78+/-4kg; control, n=3; ShamOP, n=2; coronary microembolization [CME],
      n=10). CHF was induced under fluoroscopic guidance by multiple sequential
      microembolizations (MEs) through bolus injection of polysterol microspheres
      (90um, n=25.000) into the left main coronary artery. CME was repeated up to three
      times at 2- to 3-week intervals until animals started to develop stable signs of
      CHF. All animals were followed for 3 months. Phosphorylation of AMPK, marking the
      activated protein form, was detected by Western blotting. VEGF-A and vascular
      endothelial growth factor-receptor 2 (VEGF-R2) mRNA were detected by real-time
      polymerase chain reaction. Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was
      used as a reference housekeeping gene. All 10 CHF animals developed clinical
      signs of CHF as indicated by a significant decrease of cardiac output, decreased
      ejection fraction, as well as occurrence of tachycardia and tachypnoea. Western
      blots showed significant phosphorylation of AMPK in CME animals compared to the
      control group (phospho-adenosine monophosphate-activated protein kinase alpha)
      (GAPDH control: 0.0, CME left ventricle [LV]: 0.39+/-0.20, CME right ventricle
      [RV]: 0.53+/-0.30; P<0.05). VEGF-A and VEGF-R2 expression in CME animal
      myocardium was within the range of the control group, but this data did not reach
      statistical significance due to the small size of this group. While
      microinjection was performed into the left main coronary artery, phosphorylation
      of AMPK and expression of VEGF-A and VEGF-R2 were significantly higher in the RV
      than in the LV. Multiple sequential intracoronary MEs can effectively induce
      myocardial dysfunction with clinical and biomolecular signs of chronic ischemic
      cardiomyopathy. Quantitative analysis of biomolecular markers showed a
      significantly higher phosphorylation of AMPK in CHF animals compared with control
      myocardium.

PMID- 21092040
TI  - Cerebral oxygen metabolism during total body flow and antegrade cerebral
      perfusion at deep and moderate hypothermia.
AB  - The aim of this study is to evaluate the effect of temperature on cerebral oxygen
      metabolism at total body flow bypass and antegrade cerebral perfusion (ACP).
      Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow
      rate of 200mL/kg/min. After cooling to 18 degrees C (n=6) or 25 degrees C (n=7),
      flow was reduced to 100mL/kg/min (half-flow, HF) for 15min and ACP was initiated
      at 40mL/kg/min for 45min. Following rewarming, animals were weaned from bypass
      and survived for 4h. At baseline, HF, ACP, and 4 h post-CPB, cerebral blood flow
      (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction
      (CEO(2) ) and cerebral metabolic rate of oxygen (CMRO(2) ) were monitored.
      Regional cranial oxygen saturation (rSO(2) ) was continuously recorded throughout
      the procedure using near-infrared spectroscopy. At 18 degrees C, CBF trended
      lower at HF and ACP and matched baseline after CPB. CEO(2) trended lower at HF
      and ACP, and trended higher after CPB compared with baseline. CMRO(2) at ACP
      matched that at HF. Cranial rSO(2) was significantly greater at HF and ACP
      (P<0.001, P<0.001) and matched baseline after CPB. At 25 degrees C, CBF trended
      lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB.
      CEO(2) was equal at HF and ACP and trended higher after CPB compared with
      baseline. CMRO(2) at ACP was greater than that at HF (P=0.001). Cranial rSO(2)
      was significantly greater at HF (P=0.01), equal at ACP, and lower after CPB
      (P=0.03). Lactate was significantly higher at all time points (P=0.036, P<0.001,
      and P<0.001). ACP provided sufficient oxygen to the brain at a total body flow
      rate of 100mL/kg/min at deep hypothermia. Although ACP provided minimum
      oxygenation to the brain which met the oxygen requirement, oxygen metabolism was
      altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia
      needs further investigation.

PMID- 21092041
TI  - Inflammatory and hemostatic response to cardiopulmonary bypass in pediatric
      population: feasibility of seriological testing of multiple biomarkers.
AB  - Perioperative myocardial and cerebral damages are the major determinants of
      postoperative morbidity and mortality in pediatric cardiac surgery.
      Cardiopulmonary bypass (CPB) causes alterations in the levels of biomarkers
      related to inflammation, tissue damage, and other tissue pathologies. Early and
      accurate evaluation of inflammation and tissue damage would therefore be
      clinically useful. Our objective is to assess the suitability of using Multi
      Analyte Profiling (MAP) (Rules Based Medicine, Austin, TX, USA) in pediatric
      cardiac surgery as a potential surrogate marker of clinical outcome. MAP
      technology platform allowed us to analyze 90 different biomarkers using only
      100uL of plasma to detect any changes in the levels of 90 biomarkers. Plasma
      samples (100uL) were collected at five different time points: 1. before midline
      incision; 2. on CPB for 3-5min; 3. at the end of CPB; 4. 1h after CPB; and 5. 24h
      after CPB. After removing the outliers, the average and standard deviation of the
      values obtained from the 10 patients were calculated for each time point. The
      average values of each biomarker at each time point were then compared to each
      other and to the baseline. The pilot protocol included 10 patients (ages from 3
      months to 4 years old) with similar Jenkins risks stratifications who underwent
      nonpulsatile CPB. We detected changes in the levels of 90 biomarkers. Biomarkers
      were assessed in groups. Myeloperoxidase (MPO) and pregnancy-associated plasma
      protein A (PAPP-A) were the earliest markers to rise with 49- and 18-fold
      increases 3-5min after the onset of CPB, respectively. The most striking increase
      was noted in the heart-type fatty acid-binding protein (FABP) levels. FABP
      increased 25, 193, 151, and 4-fold at time points 2, 3, 4, and 5, respectively.
      Surges in the novel markers of injury were followed by the markers of
      inflammation (i.e., C-reactive protein, interleukins) peaking at 24h after CPB.
      This pilot study shows that it is possible to measure 90 different biomarkers
      using only a very small sample of plasma to evaluate the effects of CPB. Novel
      markers of tissue injury (FABP, PAPP-A, or MPO) are the earliest markers to rise.
      Serial monitoring of multiple biomarkers may help to predict and improve outcomes
      after pediatric cardiac surgery.

PMID- 21092042
TI  - A microfluidic device for continuous white blood cell separation and lysis from
      whole blood.
AB  - A microfluidic device, which is composed of a blood inlet, a cell lysis solution
      inlet, a bifurcation outlet containing six microchannels, and a white blood cell
      (WBC)-lysed solution outlet, is proposed in this study to separate WBCs from
      whole blood and lyse the WBCs in a continuous and near real-time fashion. The
      geometry of the microfluidic device is determined based on the bifurcation law
      and a cell crossover method. The microflow patterns of blood cells in the
      microfluidic channels are simulated by computational fluid dynamics. The
      simulation results agree with the experiment results by considering the reduction
      of blood viscosity in the microfluidic channels. The performance of the
      microfluidic device is evaluated by investigating the WBC recovery efficiency and
      the ratio of spectrophotometric absorbance of the blood sample at 260 to that at
      280nm. The WBC recovery efficiency at the main channel outlet is 97.2%. The
      measured spectrophotometric absorbance ratio of 1.82 indicates that the separated
      WBCs are completely lysed, leaving only pure DNA in the WBC-lysed solution. The
      continuous cell separation and lysis is completed within only 0.5s. Therefore, it
      is concluded that the proposed microfluidic device is promising for separating
      WBCs from whole blood without any pretreatment and lysing the WBCs in a
      continuous and near real-time fashion. The proposed microfluidic device may be
      applicable to a lab-on-a-chip for blood analysis.

PMID- 21092043
TI  - Impact of tubing length on hemodynamics in a simulated neonatal extracorporeal
      life support circuit.
AB  - During extracorporeal life support (ECLS), a large portion of the hemodynamic
      energy is lost to various components of the circuit. Minimization of this loss in
      the circuit leads to better vital organ perfusion and decreases the risk of
      systemic inflammation. In this study, we evaluated the hemodynamic properties of
      differing lengths of tubing in a simulated neonatal ECLS circuit. The neonatal
      ECLS circuit used in this study included a Capiox Baby RX05 oxygenator (Terumo
      Corporation, Tokyo, Japan), a Rotaflow centrifugal pump (MAQUET Cardiopulmonary
      AG, Hirrlingen, Germany), and a heater and cooler unit. An 8Fr Biomedicus
      arterial and a 10Fr Biomedicus venous cannula were connected to the
      pseudopatient. One-fourth inch tubing was used for both the arterial and the
      venous line. A Hoffman clamp was located upstream from the pseudopatient to
      maintain a certain patient pressure. Three pressure transducers were placed at
      different sites: postoxygenator, prearterial cannula, and postarterial cannula.
      The system was primed with Lactated Ringer's solution; human blood was then added
      to maintain a hematocrit of 40%. The volume of the pseudopatient was 500mL. We
      hemodynamically evaluated three circuits with different lengths of tubing: 6, 4,
      and 2 feet (182.88, 121.92, and 60.96 cm, respectively) for both arterial and
      venous lines; the priming volumes including all of the components of the circuits
      were 195, 155, and 115mL, respectively. In each circuit, we measured the pressure
      drops of the arterial tubing and the arterial cannula, as well as the flow rates
      at different rpm (1750-3000, 250 intervals) under three patient pressures (40,
      60, and 80mm Hg). All the experiments were conducted at 37 degrees C. The
      pressure drop across the arterial cannula is much larger than that of arterial
      tubing in all set-ups, especially under high flow rates. Upon cutting the tubing
      from 6 to 2 feet, the pressure drop of the arterial tubing decreased by half,
      while the pressure drop of the arterial cannula increased due to the slightly
      higher flow rates. These results suggest that compared to the arterial tubing,
      the arterial cannula has a larger impact on the hemodynamics of the circuit.
      There is a little influence of tubing length on the circuit flow rate.

PMID- 21092044
TI  - In vitro evaluation of right ventricular outflow tract reconstruction with
      bicuspid valved polytetrafluoroethylene conduit.
AB  - Conduits available for right ventricular outflow tract (RVOT) reconstruction
      eventually become stenotic and/or insufficient due to calcification. In order to
      reduce the incidence of reoperations we have developed and used a bicuspid valved
      polytetrafluoroethylene (PTFE) conduit for the RVOT reconstruction. The purpose
      of this study is to investigate the hemodynamic performance of the new design
      using a pediatric in vitro right heart mock loop. PTFE conduit has been used for
      the complete biventricular repair of 20 patients (age 1.7+/-6 years) with
      cyanotic congenital defects. To account for the large variability of conduit
      sizes, 14, 16, 22, and 24-mm conduit sizes were evaluated using an in vitro flow
      loop comprised of a pulsatile pump with cardiac output (CO) of 1.2-3.2L/min,
      bicuspid valved RVOT conduit, pulmonary artery, venous compartments, and the flow
      visualization setup. We recorded the diastolic valve leakage and pre- and post
      conduit pressures in static and pulsatile settings. In vitro valve function and
      overall hemodynamic performance was evaluated using high-speed cameras and
      ultrasonic flow probes. Three-dimensional flow fields for different in vivo
      conduit curvatures and inflow regimes were calculated by computational fluid
      dynamics (CFD) analysis to further aid the conduit design process. The average
      pressure drop over the valved conduits was 0.8+/-1.7mm Hg for the CO range
      tested. Typical values for regurgitant fraction, peak-to-peak pressure gradient,
      and effective office area were 23+/-2.1%, 13+/-2.4mm Hg, and 1.56+/-0.2 cm(2) ,
      respectively. High-speed videos captured the intact valve motion with
      asymmetrical valve opening during the systole. CFD simulations demonstrated the
      flow skewness toward the major curvature of the conduit based on the pulmonic
      curvature. In vitro evaluation of the bicuspid valved PTFE conduit coincides well
      with acceptable early clinical performance (mild insufficiency), with relatively
      low pressure drop, and intact valve motion independent from the conduit
      curvature, orientation or valve location, but at the expense of increased
      diastolic flow regurgitation. These findings benchmark the baseline performance
      of the bicuspid valved conduit and will be used for future designs to improve
      valve competency.

PMID- 21092045
TI  - Pneumatic pulsatile ventricular assist device as a bridge to heart
      transplantation in pediatric patients.
AB  - Despite the remarkable advances with the use of ventricular assist devices (VAD)
      in adults, pneumatic pulsatile support in children is still limited. We report on
      our experience in the pediatric population. A retrospective review of 17
      consecutive children offered mechanical support with Berlin Heart as a bridge to
      heart transplant from February 2002 to April 2010 was conducted. The median
      patient age was 3.9 years (75 days to 13.3 years). The median patient weight was
      14.1 kg (2.9-43kg). Before VAD implantation, all children were managed by
      multiple intravenous inotropes and mechanical ventilation (14) or extracorporeal
      membrane oxygenation (3). All patients had right ventricular dysfunction. Nine
      patients required biventricular mechanical support (BVAD), but in all other cases
      a single left ventricular assist device proved sufficient (47%). The median
      duration of VAD support was 47 days (1-168 days). The median pre-VAD pulmonary
      vascular resistance index (Rpi) was 5.7 WU/m(2) (3.5 to 14.4WU/m(2) ). Eleven
      patients (65%) were successfully bridged to heart transplantation after a median
      duration of mechanical support of 68 days (6-168 days). Six deaths occurred
      (35%), three for neurological complications, one for sepsis, and two others for
      device malfunctioning. Since 2007, the survival rate of our patients has
      increased from 43% to 80%, and the need for BVAD has decreased from 86% to 30%.
      In two patients with Rpi >10WU/m(2) , unresponsive to pulmonary vasodilatator
      therapy, Rpi dropped to 2.2 and 2WU/m(2) after 40 and 23 days of BVAD support,
      respectively. Seven patients (41%) required at least one pump change. Of 11
      patients undergoing heart transplant, four developed an extremely elevated (>60%)
      panel reactive antibody by enzyme-linked immunosorbent assay, confirmed by
      Luminex. All of them experienced at least one acute episode of rejection in the
      first month after heart transplant, needing plasmapheresis. The survival rate
      after heart transplantation was 100% with a median follow-up of 25.4 months (6
      days to 7.7 years). Mechanical support in children with end-stage heart failure
      is an effective strategy as a bridge to heart transplantation with a reasonable
      morbidity and mortality. BVAD support may offer an additional means to reverse
      extremely elevated pulmonary vascular resistance.

PMID- 21092046
TI  - Development of a force-reflecting robotic platform for cardiac catheter
      navigation.
AB  - Electrophysiological catheters are used for both diagnostics and clinical
      intervention. To facilitate more accurate and precise catheter navigation,
      robotic cardiac catheter navigation systems have been developed and
      commercialized. The authors have developed a novel force-reflecting robotic
      catheter navigation system. The system is a network-based master-slave
      configuration having a 3-degree of freedom robotic manipulator for operation with
      a conventional cardiac ablation catheter. The master manipulator implements a
      haptic user interface device with force feedback using a force or torque signal
      either measured with a sensor or estimated from the motor current signal in the
      slave manipulator. The slave manipulator is a robotic motion control platform on
      which the cardiac ablation catheter is mounted. The catheter motions-forward and
      backward movements, rolling, and catheter tip bending-are controlled by
      electromechanical actuators located in the slave manipulator. The control
      software runs on a real-time operating system-based workstation and implements
      the master/slave motion synchronization control of the robot system. The
      master/slave motion synchronization response was assessed with step, sinusoidal,
      and arbitrarily varying motion commands, and showed satisfactory performance with
      insignificant steady-state motion error. The current system successfully
      implemented the motion control function and will undergo safety and performance
      evaluation by means of animal experiments. Further studies on the force feedback
      control algorithm and on an active motion catheter with an embedded actuation
      mechanism are underway.

PMID- 21092047
TI  - Filament support spindle for an intravascular cavopulmonary assist device.
AB  - We are developing an intravascular axial flow blood pump to support adolescent
      and adult Fontan patients. To protect the blood vessel, this pump has an outer
      cage with radially arranged filaments and a newly designed spindle at the pump
      outlet. The outlet spindle is included to limit the axial movement of the rotor
      and to house bearings that support the rotor. This study evaluates the impact of
      the outlet spindle on pump performance using computational fluid dynamics (CFD)
      and experimental testing of a prototype configuration. We measured the pressure
      flow performance of the prototype with a protective cage using a blood analog
      fluid. The pump with the cage filaments and spindle generated 1 to 16mmHg of
      pressure rise for flow rates of 1 to 4L/min at 4000 to 7000rpm. The difference
      between the CFD predictions and experimental results was found to be
      approximately 9.8%. Scalar stress levels remained below 570Pa with exposure times
      on the order of 1.5s. These results are acceptable and support the continued
      development of this cavopulmonary assist device with an outlet spindle to
      reinforce the protective cage filament design.

PMID- 21092048
TI  - A three-dimensional bioprinting system for use with a hydrogel-based biomaterial
      and printing parameter characterization.
AB  - Bioprinting is an emerging technology for constructing tissue or bioartificial
      organs with complex three-dimensional (3D) structures. It provides high-precision
      spatial shape forming ability on a larger scale than conventional tissue
      engineering methods, and simultaneous multiple components composition ability.
      Bioprinting utilizes a computer-controlled 3D printer mechanism for 3D biological
      structure construction. To implement minimal pattern width in a hydrogel-based
      bioprinting system, a study on printing characteristics was performed by varying
      printer control parameters. The experimental results showed that printing pattern
      width depends on associated printer control parameters such as printing flow
      rate, nozzle diameter, and nozzle velocity. The system under development showed
      acceptable feasibility of potential use for accurate printing pattern
      implementation in tissue engineering applications and is another example of novel
      techniques for regenerative medicine based on computer-aided biofabrication
      system.

PMID- 21092049
TI  - Feasibility of implantable cardioverter defibrillator treatment in five patients
      with familial Friedreich's ataxia--a case series.
AB  - Friedreich's ataxia (FRA) is an autosomal recessive disease of the central
      nervous system that is associated with familial cardiomyopathy. Cardiac
      involvement is seen in more than 90% of the patients and is the most common cause
      of death in these patients. We present a case series and discuss the indications
      for implantable cardioverter defibrillator (ICD) implantation in FRA with review
      of the literature. Five pediatric patients who suffer from FRA (four female and
      one male, mean age 17.4 years) underwent ICD implantation between 2007 and 2008
      in the University Hospital of Goettingen. The diagnosis of FRA was established by
      standard clinical criteria and proven in each case by genotyping at the frataxin
      locus. The time from diagnosis to ICD implantation was 10.4+/-1.73 years (range 8
      15 years). All patients received transvenous lead systems. There were no
      intraoperative and postoperative complications. At the latest follow-up, the
      neuromuscular symptoms exhibited no further progress and no ICD activations were
      noticed. Only minor repolarization changes were seen on electrocardiogram. All
      patients had normal echocardiographic findings and no angina has been reported.
      Coronary angiographies were normal. It is evident that many FRA patients develop
      ventricular dysfunction. In the absence of a definitive surgical cure an ICD is
      generally indicated in young patients with hemodynamically significant sustained
      ventricular tachyarrhythmias for prevention of sudden cardiac death. Our
      experience implies the safe use of ICD in children with FRA.

PMID- 21092050
TI  - Visceral adipose tissue accumulation and cardiovascular disease risk profile in
      postmenopausal women with impaired glucose tolerance or type 2 diabetes.
AB  - OBJECTIVE: Women with impaired glucose tolerance (IGT) and type 2 diabetes (T2D)
      are more at risk of cardiovascular disease. The aim of this study was to test the
      hypothesis that increased visceral adipose tissue (VAT) could explain to a large
      extent alterations in the cardiovascular disease risk profile of postmenopausal
      women with IGT or T2D. DESIGN, PATIENTS AND MEASUREMENTS: Sixty-two women with
      normal glucose tolerance (NGT), 33 with IGT and 18 with de novo diagnosed T2D
      were tested. The sample was further divided into five groups: (i) NGT-low VAT
      (<130 cm(2) ); (ii) NGT-high VAT (>=130 cm(2)); (iii) IGT-low VAT (<130 cm(2) );
      (iv) IGT-high VAT (>=130 cm(2) ) and (v) T2D. RESULTS: Women with T2D, women with
      IGT-high VAT and those with NGT-high VAT all had lower insulin sensitivity as
      determined by the euglycaemic-hyperinsulinaemic clamp (M_I), higher triglyceride
      (TG), lower HDL(2)-cholesterol (chol) levels and higher levels of high
      sensitivity C-reactive protein than women with NGT-low VAT. Only differences in
      M_I and early insulin response (EIR) were observed between women with IGT-high
      VAT and those with NGT-high VAT (lower values in IGT-high VAT). Women with T2D
      had lower M_I and EIR as well as higher plasma TG and lower plasma Apo A1 and HDL
      chol concentrations than women with NGT-high VAT. CONCLUSIONS: Our results
      suggest that increase in VAT accumulation usually found in women with IGT
      explains to a large extent the deterioration in their plasma lipid-lipoprotein
      and inflammatory profile. However, factors other than VAT are involved in
      explaining the high TG-low HDL dyslipidaemia observed in women with T2D.

PMID- 21092051
TI  - Factors associated with plasma ghrelin level in Japanese general population.
AB  - OBJECTIVE: Ghrelin is a novel gastric peptide identified in 1999 as a 'hunger
      hormone'. Plasma ghrelin level is decreased in human obesity. Factors associated
      with ghrelin have been mainly investigated in western countries where the
      prevalence of obesity is high. The aim of this study is to examine factors
      associated with plasma ghrelin in a Japanese general population where obesity is
      not so common. METHODS: Fasting ghrelin levels were measured by ELISA in 638
      subjects in 2005-2007. We measured body mass index (BMI), waist circumference and
      blood pressure. Blood was drawn in the morning after a 12-h fast for
      determinations of ghrelin, lipid, glucose (FPG), insulin, estimated glomerular
      filtration rate (eGFR) and uric acid levels. Univariate and multiple stepwise
      regression analyses were performed to find out factors associated with ghrelin.
      RESULTS: In our population, the mean BMI was 23.8 kg/m(2) , indicating a nonobese
      population. Results of univariate analysis showed that age (P<0.001), BMI
      (P<0.001), waist (P<0.001), triglycerides (P<0.01), FPG (P<0.01), insulin
      (P<0.001) and uric acid (P<0.05) were inversely associated with ghrelin. High
      density lipoprotein (HDL) cholesterol (P<0.001) and eGFR (P<0.05) were positively
      associated with ghrelin. Men had lower ghrelin levels than women (P<0.001).
      Results of the multiple stepwise regression analysis revealed that age (P<0.001;
      inversely), female gender (P<0.001), insulin (P<0.001; inversely), HDL
      cholesterol (P=0.005), BMI (P=0.01; inversely) and uric acid (P=0.045; inversely)
      were significantly and independently associated with ghrelin. CONCLUSIONS: The
      present study demonstrated that age and gender affected plasma ghrelin levels
      more than BMI. This may well be because of the low prevalence of overweight in
      our population.

PMID- 21092052
TI  - Androgen deprivation therapy in men with prostate cancer: how should the side
      effects be monitored and treated?
AB  - Adverse effects of androgen deprivation therapy (ADT) are a consequence of the
      induced sex steroid deficiency. ADT increases fat mass leading to insulin
      resistance and diabetes, and accelerates bone loss causing increased fracture
      risk. Given the high prevalence of cardiovascular disease and reduced bone
      density in ADT-naive men with prostate cancer, the benefits of ADT have to be
      carefully weighed against its side effects, especially as a diagnosis of prostate
      cancer does not alter the life expectancy for most men. Men commencing ADT should
      be counselled about and be carefully monitored for these and other ADT-induced
      complications, which include fatigue, sexual dysfunction, hot flushes and
      anaemia. ADT-associated side effects should be prevented and treated in order
      that ADT-induced toxicity does not outweigh its benefits. Future clinical trials
      are needed: first, to better define the effects of ADT on survival in men with
      localized prostate cancer or with biochemical prostate-specific antigen
      recurrence; second, to delineate ADT-associated harm, especially with respect to
      cardiovascular events and fractures; and third, to test the efficacy of
      interventions designed to minimize ADT-related adverse outcomes. Such information
      will be essential to better quantify the risk-benefit ratio of ADT in the
      individual man with prostate cancer.

PMID- 21092053
TI  - Implant surface characteristics influence the outcome of treatment of peri
      implantitis: an experimental study in dogs.
AB  - AIM: To analyse the effect of surgical treatment of peri-implantitis without
      systemic antibiotics at different types of implants. MATERIAL AND METHODS: Four
      implants representing four different implant systems - turned (Biomet 3i),
      TiOblast (Astra Tech AB), SLA (Straumann AG) and TiUnite (Nobel Biocare AB) were
      placed in the left side of the mandible in six dogs, 3 months after tooth
      extraction. Experimental peri-implantitis was initiated by placement of ligatures
      and plaque formation. The ligatures were removed when about 40-50% of the
      supporting bone was lost. Four weeks later, surgical therapy including mechanical
      cleaning of implant surfaces was performed. No systemic antibiotics or local
      chemical antimicrobial therapy were used. After 5 months, block biopsies were
      obtained and prepared for histological analysis. RESULTS: Two of the TiUnite
      implants were lost after surgical therapy. Radiographic bone gain occurred at
      implants with turned, TiOblast and SLA surfaces, while at TiUnite implants
      additional bone loss was found after treatment. Resolution of peri-implantitis
      was achieved in tissues surrounding implants with turned and TiOblast surfaces.
      CONCLUSION: Resolution of peri-implantitis following treatment without systemic
      or local antimicrobial therapy is possible but the outcome of treatment is
      influenced by implant surface characteristics.

PMID- 21092054
TI  - Local tolerance and efficiency of two prototype collagen matrices to increase the
      width of keratinized tissue.
AB  - AIM: to evaluate the local tolerance and efficiency of two experimental collagen
      matrices to increase the width of keratinized tissue. METHODS: in 12 pigs, two
      apically positioned flaps were prepared on both sides of the mandible. The
      denuded defect areas were randomly covered with one of two experimental porcine
      derived collagen matrices (M1; M2). The other defect area was left untreated
      (control). At 1 and 6 months, clinical measurements for the width and thickness
      of the keratinized tissue were recorded. At 6 months, all animals were
      sacrificed. Descriptive and semi-quantitative histologic analyses were performed.
      For statistical analysis, the Kruskal-Wallis test and the Mac Nemar test were
      applied. RESULTS: the collagen matrices integrated well into the surrounding
      tissue without any signs of inflammation. The thickness and width of the
      keratinized tissue increased significantly over 6 months in all the groups,
      resulting in slightly more favourable results for M1 (compared with M2) with
      respect to the thickness and for M2 (compared with M1) with respect to the width
      of keratinized tissue. No statistically significant differences were observed for
      any of the evaluated clinical and histologic parameters among the three treatment
      modalities. CONCLUSIONS: within the limits of this animal study, the prototype
      collagen matrices can be used safely to increase the width of keratinized tissue.

PMID- 21092055
TI  - Prevalence and distribution of Aggregatibacter actinomycetemcomitans serotypes
      and the JP2 clone in a Greek population.
AB  - AIM: to investigate the distribution of Aggregatibacter actinomycetemcomitans
      serotypes and the prevalence of the JP2 clone in subgingival samples of Greek
      subjects. MATERIALS AND METHODS: two hundred and twenty eight subjects
      participated in the present study. Each contributed with one pooled subgingival
      sample from the mesiobuccal surface of the four first molars. Samples were
      analysed using polymerase chain reaction for five serotypes of A.
      actinomycetemcomitans and the JP2 clone, using primers and conditions described
      previously. Subjects were stratified according to periodontal status (untreated
      periodontitis, non-periodontitis and periodontitis patients receiving supportive
      treatment). Comparisons between and within groups were performed by applying non
      parametric tests (Kruskall-Wallis, Pearson chi(2) , z-test with Bonferroni's
      corrections and Kramer's V-test) at p=0.05 level. RESULTS: a.
      actinomycetemcomitans was detected statistically more frequently in untreated
      patients (27.5%) compared with the other two groups (11.7% for non-periodontitis
      and 10% for periodontitis patients receiving supportive treatment). No
      statistical differences were observed concerning the distribution of serotypes
      among groups (z-test with Bonferroni's corrections p>0.05). Serotype c was more
      predominant within the periodontally diseased groups (Kramer's V-test p<0.05).
      The JP2 clone was not detected. CONCLUSIONS: a. actinomycetemcomitans serotype b
      was not statistically correlated with periodontal disease in the investigated
      sample and the utility of microbiological testing before antimicrobial
      administration is emphasized.

PMID- 21092056
TI  - Maxillary anterior and mandibular posterior residual ridge resorption in patients
      wearing a mandibular implant-retained overdenture.
AB  - The mandibular implant-retained overdenture could improve masticatory function
      compared to the conventional complete denture. However, increased forces exerted
      by the overdenture could increase residual ridge resorption of the maxillary
      anterior and mandibular posterior areas. The aim of this study was to compare the
      effect of the mandibular implant-retained overdenture using two or four dental
      implants, or the conventional complete denture on resorption of the residual
      ridge of the maxillary anterior and mandibular posterior areas over a period of
      10 years. In total, 120 patients, 30 patients treated with an overdenture on two
      implants (two-implant group), 30 patients with an overdenture on four implants
      (four-implant group) and 60 patients treated with a conventional full denture
      (conventional group), participated in this study. On panoramic radiographs, made
      before and 10 years after treatment, proportional area measurements were applied
      to determine changes in bone height. After 10 years, a statistically significant
      amount of bone resorption had occurred in the anterior maxilla in the two-implant
      group and in the four-implant group. A significant amount of bone resorption had
      occurred in the posterior mandible in all three groups. There were no
      statistically significant differences between the groups in both areas. Patients
      presented large individual differences. It is concluded that patients
      rehabilitated with implant-retained mandibular overdentures are not subjected to
      more residual ridge resorption in the anterior maxilla when compared to patients
      wearing a conventional full denture. Regarding the mandibular posterior residual
      ridge, resorption was irrespective of wearing an implant-retained mandibular
      overdenture or a conventional mandibular denture.

PMID- 21092057
TI  - Medallion-like dermal dendrocyte hamartoma: a case misdiagnosed as neurofibroma.
AB  - Medallion-like dermal dendrocyte hamartoma is a rare congenital lesion, comprised
      of a benign dermal proliferation of fusiform cells that stain positive for CD34,
      often positive for factor XIIIa, and negative for S100. It has a highly
      characteristic clinical presentation consisting of a well-circumscribed atrophic
      and wrinkled patch located on the upper trunk or neck that remains stable with
      time. We report a case of an 11-year-old boy with a typical medallion-like dermal
      dendrocyte hamartoma on the nape of the neck that was previously misdiagnosed as
      neurofibroma on the basis of initial histological examination that was later
      reevaluated due to lack of clinical correlation. Three previously-reported cases
      of medallion-like dermal dendrocyte hamartoma also have had a previous
      histological misdiagnosis of probable neurofibroma; other reported cases have
      been misdiagnosed as congenital atrophic dermatofibrosarcoma protuberans.
      Clinical correlation and immunostaining are particularly important for the
      recognition of this rare benign lesion.

PMID- 21092058
TI  - Acute mechanical effect of right ventricular pacing at different sites using
      velocity vector imaging.
AB  - OBJECTIVE: Velocity vector imaging (VVI) allows noninvasive measurement of left
      ventricular (LV) strain and rotation angle-independently. We investigated strain,
      rotation and myocardial synchrony when pacing at different sites in the right
      ventricle to determine which site yields the most physiological pacing, as
      determined with VVI imaging. METHOD: Thirty-one patients with normal LV function
      referred for elective electrophysiology exam were used in this study. Catheters
      (6F quadripolar) were positioned in the right atrium, right ventricular apex,
      right ventricular outflow tract, and His bundle after electrophysiology exam was
      done. Regional and global LV circumferential strain (CS), radial strain (RS), and
      LV rotation of LV short-axis measurements were obtained. Two dyssynchrony
      parameters (AS-P delay and SDt(6S)) of CS and RS were obtained. Compare these
      values among each pacing, respectively. RESULT: CS, RS, and twist, which
      represent the LV systolic function, were significantly reduced in RVOT pacing and
      RVA pacing than RA pacing. Two dyssynchrony parameters (AS-P delay and SDt(6S))
      were significantly longer in response to RVOT or RVA pacing compared to RA
      pacing. No significant differences were found between RVOT pacing and RVA pacing.
      CS and RS were obviously reduced in the regions surrounding the pacing site.
      There was no significant difference in CS, RS, twist, and mechanical dyssynchrony
      parameters when comparing His and RA pacing. CONCLUSION: Among these alternate
      right ventricular pacing locations, His bundle pacing is most like physiological
      pacing. Both RVOT pacing and RVA pacing worsen the normal LV systolic function
      with regard to strain, twist, and mechanical dyssynchrony along the LV short
      axis.

PMID- 21092059
TI  - Clinical indications for intravascular ultrasound imaging.
AB  - Intravascular ultrasound (IVUS) is a catheter-based imaging modality, which
      provides high resolution cross-sectional images of the coronary arteries. Unlike
      angiography, which displays only the opacified luminal silhouette, IVUS permits
      imaging of both the lumen and vessel wall and allows characterization of the type
      of the plaque. Although IVUS provides accurate quantitative and qualitative
      information regarding the lumen and outer vessel wall, it is not routinely used
      during coronary angiography or in angioplasty procedures because the risk to
      benefit ratio (additional expense, procedural time, certain degree of risk, and
      complication versus improvement in the outcome) does not justify routine
      utilization. Nevertheless, there are situations where IVUS is extremely useful
      tool both for diagnosis and management so the aim of this review is to summarize
      the indications for IVUS imaging in the contemporary clinical practice.

PMID- 21092060
TI  - A simple and high-yield method for preparation of rat microglial cultures
      utilizing Aclar plastic film.
AB  - Microglia are implicated in both neuroprotection and neurodegeneration, and are a
      key area of interest with respect to various CNS diseases. Until now, primary
      microglia prepared by various isolation methods have been widely used to
      investigate their role in CNS diseases. However, there are some problems with the
      current isolation methods, such as the numbers of animals required in order to
      obtain sufficient numbers of microglial cells due to low yields, and also the
      long periods of culture required. We herein describe a simple, high-yield method
      for isolating not only primary microglia, but also immortalized microglial cells.
      Our method allows for the isolation of an almost pure population of microglia
      with only two steps. First, a primary mixed neural culture was prepared from the
      brains of 3-day-old postnatal rats. Next, primary microglia were collected for 2
      h by adhesion to Aclar plastic film. The average yield by this method was
      approximately 50 times higher than that of the conventional shaking method.
      Immortalized microglial cells could also be prepared based on this procedure. A
      plasmid vector encoding the SV40 large T antigen was transfected into the mixed
      neural culture using a calcium phosphate precipitation method. Then,
      proliferating immortalized microglia were collected after several weeks in a
      similar fashion. Several clones were obtained by limited dilution and one of the
      immortalized cell lines was designated SMK. The SMK cells exhibited markers
      specific for the microglia lineage, including Iba-1, CD11b, CD45, CD68, major
      histocompatibility complex (MHC) class I and MHC class II, but not for the
      astrocyte-specific markers, GFAP and glutamate aspartate transporter. SMK also
      showed phagocytic activity. In conclusion, this method resulted in a high-yield
      preparation of microglial cultures with ease and reproducibility.

PMID- 21092061
TI  - Spatiotemporal expression of PSD-95 in Fmr1 knockout mice brain.
AB  - To investigate and compare the spatial and temporal expression of post-synaptic
      density-95 (PSD-95) in Fmr1 knockout mice (the animal model of fragile X
      syndrome, FXS) and wild-type mice brain, on postnatal day 7 (P7), P14, P21, P28
      and P90, mice from each group were decapitated, and three principal brain regions
      (cerebral cortex, hippocampus and cerebellum) were obtained and stored for later
      experiments. PSD-95 mRNA in the three brain areas was analyzed with quantitative
      RT-PCR. PSD-95 protein was measured by immunohistochemical staining and Western
      blot. In the three principal brain areas of Fmr1 knockout mice and wild-type
      mice, the expression of PSD-95 mRNA and protein were detected at the lowest
      levels on P7, and then significantly increased on P14, reaching the peak levels
      in adolescents or adults. Moreover, it was found that PSD-95 mRNA and protein in
      the hippocampus were significantly decreased in Fmr1 knockout mice during the
      developmental period (P7, P14, P21 and P28) as well as at adulthood (P90) (P <
      0.05, and P < 0.01, respectively). However, there was no significant difference
      of expression of PSD-95 in the cortex and cerebellum between Fmr1 knockout and
      wild mice. The expression of PSD-95 in the hippocampus might be regulated by
      fragile X mental retardation protein (FMRP) during mice early developmental and
      adult periods. It is suggested that impairment of PSD-95 is possibly involved in
      hippocampal-dependent learning defects, which are common in people with FXS.

PMID- 21092062
TI  - Rhabdoid glioblastoma: case report and literature review.
AB  - Rhabdoid glioblastoma is a recently described entity in which a glioblastoma is
      associated with a rhabdoid component. Although rhabdoid glioblastoma has not
      appeared in the new World Health Organization classification of tumors of the
      CNS, it has a specific morphological feature and highly aggressive clinic
      process. Up to now, there have been six cases of rhabdoid glioblastoma reported
      in the literature. We report rhabdoid glioblastoma in the right front temporal
      lobe from a 31-year-old Chinese man. This tumor consisted of rhabdoid tumor cells
      with an eccentric nucleus and an eosinophilic cytoplasm. The tumor had an area
      appearing to be glioblastoma with microvascular proliferation and necrosis, and
      lacked a primitive neuroectodermal tumor component, and a mesenchymal component.
      Vimentin, epithelial membrane antigen, GFAP and integrase interactor (INI-1)
      expression were found in the tumor cells. Genetic abnormalities which include
      monosomy or a deletion of chromosome 22 were not found in this tumor. After 3
      months post-surgery, the tumor was widespread in leptomeningia and the patient
      died. In conclusion, rhabdoid glioblastoma is a rare glioblastoma with poor
      prognosis; the differential diagnosis contained other rhabdoid tumors. This case
      will contribute to the profile of rhabdoid glioblastoma with typical morphology
      and immunophenotype, genetic and clinic features.

PMID- 21092064
TI  - Rosette-forming glioneuronal tumor of the fourth ventricle with advanced
      microvascular proliferation--a case report.
AB  - Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently
      described novel type of primary brain tumor that was included into the current
      WHO classification of CNS tumors. It is a very rare, slowly growing, mixed
      neoplasm at cerebellar localization with distinctive morphological pattern. We
      present an unusual case of a 20-year-old patient with RNGT of the fourth
      ventricle with advanced microvascular proliferation. MRI revealed the solid
      cystic tumor mass largely involving the cerebellar vermis and left hemisphere
      with compression of the fourth ventricle. Microscopically, the tumor showed
      classical architectural pattern with two distinctive components. The main
      component consisted of neurocytic rosettes formed by round, isomorphic nuclei
      arranged around eosinophilic, fibrillar cores with strong synaptophysin
      expression. The perivascular rosettes with cell arrangement along blood vessels
      were observed only sporadically. The second neoplastic component consisted of
      spindle or stellate astroglial cells with piloid process and Rosenthal fibers,
      strongly resembling pilocytic astrocytoma. Focally, the astroglial cells showed
      increased cellularity but without marked nuclear atypia. The glial part of the
      tumor revealed advanced proliferation of microvessels. The vessels of glomeruloid
      type exhibited multilayered endothelial proliferation and marked mitotic
      activity. MIB1 labelling index was generally low; however, in areas exhibiting
      microvascular proliferation its expression was significantly increased up to 20%.
      This report demonstrates the unique case of RGNT with conspicuous microvascular
      proliferation of glomeruloid type and extensive endothelial proliferation. As
      there is still limited clinical experience with RGNT, further studies are
      necessary to evaluate the biology of this type of tumor.

PMID- 21092063
TI  - Immune surveillance of the normal human CNS takes place in dependence of the
      locoregional blood-brain barrier configuration and is mainly performed by
      CD3(+)/CD8(+) lymphocytes.
AB  - Despite the blood-brain barrier (BBB) the human CNS is continuously screened by
      blood-derived immunological cells. In certain brain areas the local BBB
      configuration grants passage of large molecules, whereas others are better
      shielded. We investigated whether these regional BBB compositions are paralleled
      by differences in the degree of cellular immunosurveillance by investigating
      tissue from 23 normal human brains for several CD markers, FoxP3, granzyme B, and
      perforin. Our results provide evidence that immunosurveillance is associated with
      locoregional BBB configuration and is mainly performed by CD3(+)/CD8(+)/granzyme
      B(-)/perforin(-) lymphocytes.

PMID- 21092065
TI  - Effects of herbal preparation on libido and semen quality in boars.
AB  - The objective of this study was to investigate the effects of a preparation from
      herbal extracts (PHE) on libido and semen quality in breeding artificial
      insemination boars. Ten fertile boars were divided into control and experimental
      groups according to significant difference of libido. There were no differences
      in semen quality between groups. Animals were fed a commercial feeding mixture
      for boars. The feeding mixture for the experimental group was enriched with PHE,
      which was prepared from Eurycoma longifolia, Tribulus terrestris and Leuzea
      carthamoides. Duration of the experiment was 10 weeks. Samples of ejaculate were
      collected weekly. Libido was evaluated according to a scale of 0-5 points. Semen
      volume, sperm motility, percentage of viable spermatozoa, sperm concentration,
      morphologically abnormal spermatozoa, daily sperm production and sperm survival
      were assessed. Amounts of mineral components and free amino acids were analysed
      in seminal plasma. Significant differences were found in these parameters: libido
      (4.05 +/- 0.22 vs 3.48 +/- 0.78; p < 0.001), semen volume (331.75 +/- 61.91 vs
      263.13 +/- 87.17 g; p < 0.001), sperm concentration (386.25 +/- 107.95 vs 487.25
      +/- 165.50 * 10(3) /mm(3); p < 0.01), morphologically abnormal spermatozoa (15.94
      +/- 11.08 vs 20.88 +/- 9.19%; p < 0.001) and Mg concentration (28.36 +/- 11.59 vs
      20.27 +/- 13.93 mm; p < 0.05). The experimental group's libido was increased by
      20% in comparison with the beginning of the experiment. Results of this study
      showed positive effect of PHE on libido and some parameters of boar semen
      quality.

PMID- 21092066
TI  - Multiorgan engraftment of human somatic cells in swine foetuses after intra
      blastocyst transplantation.
AB  - Adult human stem cells, mainly from hematopoietic lineage, have been injected
      into developing pre-immune animal foetuses, and xenogenic engraftment of liver
      and other organs has been reported. We isolated a rare cell population from adult
      human liver, fat and skin. Colonies with few cells became visible as early as 2-3
      days, and a fully formed colony took 10-14 days to form. These colonies were
      named as liver-derived cell lines (LDCs), fat-derived cell lines (FDCs) and skin
      derived cell lines (SDCs). All these cells express few pluripotency markers like
      Klf4, c-myc and Sox2. Pig blastocysts were injected with LDCs, FDCs and SDCs and
      transferred to recipient pigs. We achieved an overall pregnancy rate of 71.4% at
      day 35. The foetuses were analysed for human cell chimerism in liver, kidney and
      heart both by RT-PCR and real-time PCR using primers specific to human and pig
      mitochondrial DNA. The percentage of foetuses showing chimerism was 17.4% (4/23),
      12.5% (2/16) and 11.1% (1/9) for LDCs, FDCs and SDCs, respectively. Of these,
      42.9% (three out of seven) showed chimerism in liver and 71.4% (five out of
      seven) showed kidney chimerism. However, we did not detect any chimerism in the
      heart. The level of chimerism varied and was in the range of one human cell per
      one hundred thousand to one million pig cells.

PMID- 21092067
TI  - The stress response of frequently electroejaculated rams to electroejaculation:
      hormonal, physiological, biochemical, haematological and behavioural parameters.
AB  - Electroejaculation (EE) is a technique widely used to collect semen in ruminants,
      which produces a stress response with negative effects on animal welfare. The aim
      of this paper was to characterize the stress response during conventional EE in
      rams that have been frequently electroejaculated. Blood samples were collected
      since 20 min before and until 120 min after electroejaculating 10 rams.
      Electroejaculation affected hormone concentration, as cortisol increased, and
      testosterone decreased after EE. Heart and respiratory rate increased 10 min
      after EE. Several blood parameters, such as glycaemia, an increase in total
      protein and creatine kinase concentrations and a decrease in haematocrit,
      haemoglobin, red blood cell and alkaline phosphatase concentrations. The rams
      vocalized 13.8 +/- 2.4 times, and the largest length of vocalizations during EE
      was associated with the numbers of pulses in which the rams ejaculated. In this
      paper, we provide a complete characterization of the stress response to EE in
      rams. We showed that although rams have been frequently electroejaculated, an
      important stress response including changes in respiratory rate, testosterone
      concentrations, haematological and biochemical parameters were observed, besides
      the changes in cortisol concentrations and heart rate, suggesting that rams were
      not habituated to EE. In addition, we described the main parameters of
      vocalizations and its relation with the moment of EE. The information displayed
      on the frequent use of EE in the rams should be considered in relation to the
      welfare implications.

PMID- 21092068
TI  - Rapid effects of corticosterone in the mouse dentate gyrus via a nongenomic
      pathway.
AB  - Corticosterone activates two types of intracellular receptors in the rodent
      brain: the high affinity mineralocorticoid receptor (MR) and lower affinity
      glucocorticoid receptor (GR). These receptors act as transcriptional regulators
      and mediate slow changes in neuronal activity in a region-dependent manner. For
      example, in CA1 pyramidal cells, corticosterone slowly changes Ca(2+) currents
      and glutamate transmission but dentate granule cells appear to be resistant.
      Recent studies have shown that corticosteroids also exert rapid MR-dependent,
      nongenomic effects on hippocampal CA1 cells [e.g. increasing the frequency of
      miniature excitatory postsynaptic currents (mEPSCs)]. In the present study, we
      investigated whether dentate granule cells are also resistant to the rapid
      effects of corticosterone. We found that, comparable to the CA1 area,
      corticosterone quickly and reversibly increases mEPSC frequency but not amplitude
      of dentate cells. This effect did not require protein synthesis and displayed the
      pharmacological profile of an MR- rather than GR-dependent event. These data
      support the hypothesis that, unlike the slow gene-mediated effects of
      corticosterone, rapid hormonal actions are quite similar for CA1 and dentate
      cells.

PMID- 21092069
TI  - Molybdenum isotope fractionation by cyanobacterial assimilation during nitrate
      utilization and N2 fixation.
AB  - We measured the delta98Mo of cells and media from molybdenum (Mo) assimilation
      experiments with the freshwater cyanobacterium Anabaena variabilis, grown with
      nitrate as a nitrogen (N) source or fixing atmospheric N2. This organism uses a
      Mo-based nitrate reductase during nitrate utilization and a Mo-based
      dinitrogenase during N2 fixation under culture conditions here. We also
      demonstrate that it has a high-affinity Mo uptake system (ModABC) similar to
      other cyanobacteria, including marine N2-fixing strains. Anabaena variabilis
      preferentially assimilated light isotopes of Mo in all experiments, resulting in
      fractionations of -0.20/00 to -1.00/00 +/- 0.20/00 between cells and media
      (epsilon(cells-media)), extending the range of biological Mo fractionations
      previously reported. The fractionations were internally consistent within
      experiments, but varied with the N source utilized and for different growth
      phases sampled. During growth on nitrate, A. variabilis consistently produced
      fractionations of -0.3 +/- 0.10/00 (mean +/- standard deviation between
      experiments). When fixing N2, A. variabilis produced fractionations of -0.9 +/-
      0.10/00 during exponential growth, and -0.5 +/- 0.10/00 during stationary phase.
      This pattern is inconsistent with a simple kinetic isotope effect associated with
      Mo transport, because Mo is likely transported through the ModABC uptake system
      under all conditions studied. We present a reaction network model for Mo isotope
      fractionation that demonstrates how Mo transport and storage, coordination
      changes during enzymatic incorporation, and the distribution of Mo inside the
      cell could all contribute to the total biological fractionations. Additionally,
      we discuss the potential importance of biologically incorporated Mo to organic
      matter-bound Mo in marine sediments.

PMID- 21092070
TI  - Transplantation of bone marrow cells reduces CCl4 -induced liver fibrosis in
      mice.
AB  - BACKGROUND: We investigated the reversibility of liver fibrosis induced with a
      CCl(4) injection and the role of stem cells in reversing the hepatic injury.
      Furthermore, the most effective cell fraction among bone marrow cells (BMCs) in
      the repair process was analysed. METHODS: C57BL/6 mice were divided into four
      groups after 5 weeks of injection of CCl(4) : control, sacrificed after 5 weeks,
      sacrificed at 10 weeks and sacrificed 5 weeks later after GFP-donor BM
      transplantation. Liver function tests and real-time polymerase chain reaction
      (PCR) of markers indicating liver fibrosis were compared between the groups. To
      identify the most effective BMC fraction that repairs liver injury, the mice were
      divided into three groups after the injection of CCl(4) for 2 days: granulocyte
      colony stimulating factor (G-CSF) only, mononuclear cell (MNC) transplantation
      and Lin-Sca-1+c-kit+haematopoietic stem cell (HSC) transplantation. Eight days
      after transplantation, the mice were harvested and morphometric,
      immunohistochemical analyses were performed to compare the expression of
      extracellular matrix and liver fibrosis-related factors. RESULTS: The liver
      fibrosis induced by CCl(4) was not spontaneously recovered but was persistent
      until 10 weeks, but the group injected with BMCs had less fibrosis and better
      liver function. Mobilization with G-CSF increased the recovery of the injured
      liver and the best results were seen in those mice administered the MNC fraction
      and Lin-Sca-1+c-kit+HSC fraction, with no difference between the two groups.
      CONCLUSION: BMC transplantation and stem cell mobilization with G-CSF effectively
      treats liver injury in mice. These are promising techniques for autologous
      transplantation in humans with liver fibrosis.

PMID- 21092071
TI  - Significance of periductal Langerhans cells and biliary epithelial cell-derived
      macrophage inflammatory protein-3alpha in the pathogenesis of primary biliary
      cirrhosis.
AB  - BACKGROUND/AIMS: To clarify the primary biliary cirrhosis (PBC)-specific antigen
      presenting mechanism, we examined the distribution and phenotypic characteristics
      of infiltrating dendritic cells (DCs) with respect to bile ducts and the
      mechanism of migration in terms of the periductal cytokine milieu and biliary
      innate immunity. METHODS AND RESULTS: Immunohistochemistry using liver sections
      from patients with PBC and controls revealed that blood dendritic cell antigen
      (BDCA)-2(+) plasmacytoid DCs were found mainly in the portal tracts in PBC and
      the controls, but their distribution was not related to bile ducts. BDCA-1(+) and
      CD19(-) myeloid DCs were also found in portal tracts in PBC and the controls and,
      in particular, Langerin+Langerhans cells (LCs) were dominantly scattered around
      or within biliary epithelial layers of the damaged bile ducts in PBC. Moreover,
      experiments with cultured human biliary epithelial cells (BECs) showed that an LC
      attracting chemokine, macrophage inflammatory protein-3alpha, was produced by
      BECs in the response to cytokines [interleukin (IL)-1beta, tumour necrosis factor
      alpha and IL-17] and pathogen-associated molecular patterns. CONCLUSIONS: LCs
      existing around or within biliary epithelial layers are important as periductal
      antigen-presenting cells in PBC and the migration of LCs into bile ducts is
      closely associated with the periductal cytokine milieu and biliary innate
      immunity in PBC.

PMID- 21092072
TI  - Anticoagulation in cirrhosis patients: what don't we know?

PMID- 21092073
TI  - Pressure-independent cerebrovascular remodelling and changes in myogenic
      reactivity in diabetic Goto-Kakizaki rat in response to glycaemic control.
AB  - AIM: We have shown hypertrophic cerebrovascular remodelling in the Goto-Kakizaki
      (GK) rat model of diabetes. This study tested the hypotheses that (1) vascular
      remodelling develops as the disease progresses and alters myogenic reactivity of
      resistance vessels important for regulation of cerebral blood flow (CBF), and (2)
      glycaemic control prevents cerebrovascular remodelling and myogenic dysfunction.
      METHODS: Middle cerebral artery (MCA) lumen diameter, media : lumen (M : L)
      ratio, cross-sectional area (CSA) and myogenic tone were measured in 10- and 18
      week-old control Wistar and diabetic GK rats using pressurized arteriograph (n =
      8-14/group). Mean arterial blood pressure (MAP) was measured with telemetry (n =
      5/group). Additional GK rats were treated with metformin (300 mg kg(-1) day(-1) )
      for glycaemic control starting at 7 weeks after the onset of diabetes until 18
      weeks (n = 9). RESULTS: In the control group, there was no difference in
      remodelling indices, myogenic tone or MAP between ages. Eighteen week diabetic
      rats displayed increased M : L ratio and CSA, but decreased lumen diameter and
      myogenic tone compared to 10-week GK or 18-week control rats. MAP increased
      starting around 10 weeks of age and remained slightly higher in the GK rats.
      Glycaemic control normalized M : L ratio, CSA, lumen diameter and myogenic tone
      with no effect on blood pressure. CONCLUSIONS: These findings suggest that
      diabetic rats develop MCA remodelling as the disease progresses but this is
      associated with impaired myogenic reactivity which may ultimately affect CBF. Our
      results also provide evidence that glycaemic control is an effective therapeutic
      strategy to prevent cerebrovascular remodelling and dysfunction.

PMID- 21092074
TI  - Rapid and persistent selection of the K103N mutation as a majority quasispecies
      in a HIV1-patient exposed to efavirenz for three weeks: a case report and review
      of the literature.
AB  - INTRODUCTION: Selection of the K103N mutation is associated with moderately
      reduced in vitro fitness of HIV. Strains bearing K103N in vivo tend to persist,
      even in the absence of additional drug pressure, as minority quasispecies, often
      undetectable in genotyping resistance testing assays, performed at standard
      conditions. Here, we report on the rapid and long lasting selection of a K103N
      bearing strain as the dominant quasispecies after very short exposure to
      efavirenz in vivo. CASE PRESENTATION: A 55-year-old Caucasian man was switched to
      efavirenz, zidovudine and lamivudine in February 2003, while on viral suppression
      in his first-line highly active anti-retroviral treatment regimen. One month
      later, he reported inconsistent adherence and his viremia level was 5700 c/mL. He
      did not attend further checkups until September 2005, when his viral load was
      181,000 c/mL. The patient reported interrupting his medications approximately
      three weeks after simplification. The genotyping resistance testing assay was
      performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern
      with the isolate presence of the K103N mutation in the prevalent strain.
      CONCLUSION: Persistence of the K103N mutation as a majority quasispecies may
      ensue after a very short exposure to efavirenz. Our case would therefore suggest
      that the presence of the K103N mutation should always be ruled out by genotyping
      resistance testing assays, even after minimal exposures to efavirenz.

PMID- 21092075
TI  - Vulval elephantiasis as a result of tubercular lymphadenitis: two case reports
      and a review of the literature.
AB  - INTRODUCTION: Elephantiasis as a result of chronic lymphedema is characterized by
      gross enlargement of the arms, legs or genitalia, and occurs due to a variety of
      obstructive diseases of the lymphatic system. Genital elephantiasis usually
      follows common filariasis and lymphogranuloma venereum. It may follow granuloma
      inguinale, carcinomas, lymph node dissection or irradiation and tuberculosis but
      this happens rarely. Vulval elephantiasis as a consequence of extensive lymph
      node destruction by tuberculosis is very rare. We present two very unusual cases
      of vulval elephantiasis due to tuberculous destruction of the inguinal lymph
      nodes. CASE PRESENTATION: Two Indian women - one aged 40 years and the other aged
      27 years, with progressively increasing vulval swellings over a period of five
      and four years respectively - presented to our hospital. In both cases, there was
      a significant history on presentation. Both women had previously taken a complete
      course of anti-tubercular treatment for generalized lymphadenopathy. The vulval
      swellings were extremely large: in the first case report, measuring 35 * 25 cm on
      the right side and 45 * 30 cm on the left side, weighing 20 lb and 16 lb
      respectively. Both cases were managed by surgical excision with reconstruction
      and the outcome was positive. Satisfactory results have been maintained during a
      follow-up period of six years in both cases. CONCLUSIONS: Elephantiasis of the
      female genitalia is unusual and it has rarely been reported following
      tuberculosis. We report two cases of vulval elephantiasis as a consequence of
      extensive lymph node destruction by tuberculosis, in order to highlight this very
      rare clinical scenario.

PMID- 21092077
TI  - Goltz syndrome (focal dermal hypoplasia) with unilateral ocular, cutaneous and
      skeletal features: case report.
AB  - BACKGROUND: Goltz syndrome or focal dermal hypoplasia (FDH) is an uncommon
      multisystem disorder. Herein, we report a typical case of FDH with unilateral
      ocular, cutaneous and skeletal features. CASE PRESENTATION: a 4-year-old girl
      presented with microphthalmos and iris coloboma of the left eye, facial
      asymmetry, and a low-set protruding ear. Cutaneous changes included hypopigmented
      atrophic macules on the left side of the face, chest, abdomen and limbs.
      Characteristic lobster claw deformity of left hand and oligodactyly and
      syndactyly of left foot were present. CONCLUSIONS: FDH usually affects both sides
      of the body. This case represents the unusual unilateral manifestation of the
      syndrome.

PMID- 21092076
TI  - A randomized phase III study of the docetaxel/carboplatin combination versus
      docetaxel single-agent as second line treatment for patients with
      advanced/metastatic non-small cell lung cancer.
AB  - BACKGROUND: To compare the activity and toxicity of docetaxel/carboplatin (DC)
      doublet vs single agent docetaxel (D) as second-line treatment in patients with
      advanced non-small cell lung cancer (NSCLC). METHODS: Patients pre-treated with
      front-line platinum-free regimens, were randomized to receive either
      docetaxel/carboplatin (DC), (docetaxel 50 mg/m2; carboplatin AUC4; both drugs
      administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m2
      on days 1 and 15). RESULTS: Response rate was similar between the two arms (DC vs
      D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC
      arm and 34.5 months for D arm, progression free survival (PFS) was significantly
      higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while
      no significant difference was observed in terms of overall survival (OS) (DC vs
      D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated
      and grade III/IV toxicities were relatively infrequent. No toxic deaths were
      observed. CONCLUSIONS: This study has not achieved its primary objective of
      significant OS prolongation with docetaxel/carboplatin combination over single
      agent docetaxel in patients who had not received front-line docetaxel; however,
      the docetaxel/carboplatin combination was associated with a significant clinical
      benefit in terms of PFS.

PMID- 21092078
TI  - Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH
      tamoxifen.
AB  - BACKGROUND: Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies
      with poor prognosis. There are currently no standard or effective treatments for
      RTs in part because treatments are not designed to specifically target these
      tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a
      novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol,
      inhibits RT growth. Since the toxicities and narrow window of activity associated
      with flavopiridol may limit its clinical use, we tested the effect of combining
      flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam) in order to reduce the
      concentration of flavopiridol needed for inhibition of RTs. METHODS: The effects
      of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and
      apoptosis were assessed by: i) cell survival assays, ii) FACS analysis, iii)
      caspase activity assays, and iv) immunoblot analysis. Furthermore, the role of
      p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and
      apoptosis was characterized using RNA interference (siRNA) analysis. The effect
      of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also
      determined. RESULTS: We found that the combination of flavopiridol and 4OH-Tam
      potently inhibited the growth of RT cells. Low nanomolar concentrations of
      flavopiridol induced G2 arrest, which was correlated to down-modulation of cyclin
      B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol
      mediated G2 arrest, but enhanced caspase 3,7-mediated apoptosis induced by the
      drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G2 arrest, but
      enhanced flavopiridol- (but not 4OH-Tam-) mediated apoptosis, by enhancing
      caspase 2 and 3 activities. CONCLUSIONS: Combining flavopiridol with 4OH-Tam
      potently inhibited the growth of RT cells by increasing the ability of either
      drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of
      flavopiridol was enhanced by abrogation of p53. Our results warrant further
      studies investigating the combinatorial effects of flavopiridol and 4OH-Tam as a
      novel therapeutic strategy for RTs and other tumors that have been shown to
      respond to flavopiridol.

PMID- 21092079
TI  - A novel syndrome of paediatric cataract, dysmorphism, ectodermal features, and
      developmental delay in Australian Aboriginal family maps to 1p35.3-p36.32.
AB  - BACKGROUND: A novel phenotype consisting of cataract, mental retardation,
      erythematous skin rash and facial dysmorphism was recently described in an
      extended pedigree of Australian Aboriginal descent. Large scale chromosomal re
      arrangements had previously been ruled out. We have conducted a genome-wide scan
      to map the linkage region in this family. METHODS: Genome-wide linkage analysis
      using Single Nucleotide Polymorphism (SNP) markers on the Affymetrix 10K SNP
      array was conducted and analysed using MERLIN. Three positional candidate genes
      (ZBTB17, EPHA2 and EPHB2) were sequenced to screen for segregating mutations.
      RESULTS: Under a fully penetrant, dominant model, the locus for this unique
      phenotype was mapped to chromosome 1p35.3-p36.32 with a maximum LOD score of
      2.41. The critical region spans 48.7 cM between markers rs966321 and rs1441834
      and encompasses 527 transcripts from 364 annotated genes. No coding mutations
      were identified in three positional candidate genes EPHA2, EPHB2 or ZBTB17. The
      region overlaps with a previously reported region for Volkmann cataract and the
      phenotype has similarity to that reported for 1p36 monosomy. CONCLUSIONS: The
      gene for this syndrome is located in a 25.6 Mb region on 1p35.3-p36.32. The known
      cataract gene in this region (EPHA2) does not harbour mutations in this family,
      suggesting that at least one additional gene for cataract is present in this
      region.

PMID- 21092081
TI  - Effectiveness of esterified whey proteins fractions against Egyptian Lethal Avian
      Influenza A (H5N1).
AB  - BACKGROUND: Avian influenza A (H5N1) virus is one of the most important public
      health concerns worldwide. The antiviral activity of native and esterified whey
      proteins fractions (alpha- lactalbumin, beta- lactoglobulin, and lactoferrin) was
      evaluated against A/chicken/Egypt/086Q-NLQP/2008 HPAI (H5N1) strain of clade
      2.2.1 (for multiplicity of infection (1 MOI) after 72 h of incubation at 37 
      degrees C in the presence of 5% CO2) using MDCK cell lines. RESULT: Both the
      native and esterified lactoferrin seem to be the most active antiviral protein
      among the tested samples, followed by beta- lactoglobulin. alpha-Lactalbumin had
      less antiviral activity even after esterification. CONCLUSION: Esterification of
      whey proteins fractions especially lactoferrin and beta-lactoglobulin enhanced
      their antiviral activity against H5N1 in a concentration dependent manner.

PMID- 21092082
TI  - Lifetime risks of specific breast cancer subtypes among women in four
      racial/ethnic groups.
AB  - INTRODUCTION: Breast cancer comprises clinically distinct subtypes, but most risk
      statistics consider breast cancer only as a single entity. To estimate subtype
      specific lifetime breast cancer risks, we took advantage of population-based data
      for which information regarding tumor expression of estrogen receptor (ER),
      progesterone receptor (PR) and HER2/neu (HER2) was newly available. METHODS: We
      included women whose breast cancer was diagnosed in the state of California from
      2006 to 2007 and was reported to the National Cancer Institute's Surveillance,
      Epidemiology and End Results Program (N = 40,936). We calculated absolute
      lifetime and age-specific probabilities (percent, 95% confidence interval) of
      developing breast cancer subtypes defined by ER, PR, and HER2 status - luminal
      (ER and/or PR-positive, HER2-negative), HER2-positive (ER and PR-positive or
      negative, HER2-positive), and triple-negative (ER-negative, PR-negative, and HER2
      negative) - separately for white, black, Hispanic, and Asian women. RESULTS: The
      luminal breast cancer subtype predominates across racial/ethnic groups, with
      lifetime risk lowest in Hispanic women (4.60%, 4.41-4.80%) and highest in white
      women (8.10%, 7.94-8.20%). HER2-positive breast cancer varies less by race (1.56
      1.91%). Lifetime risk of triple-negative breast cancer is highest in black women
      (1.98%, 1.80-2.17%), compared to 0.77% (0.67-0.88%) for Asians, 1.04% (0.96
      1.13%) for Hispanics and 1.25% (1.20-1.30%) for whites. Across racial/ethnic
      groups, nearly half of all luminal breast cancers occur after age 70.
      CONCLUSIONS: These absolute risk estimates may inform health policy and resource
      planning across diverse populations, and can help patients and physicians weigh
      the probabilities of developing specific breast cancer subtypes against competing
      health risks.

PMID- 21092083
TI  - Baculovirus display of single chain antibody (scFv) using a novel signal peptide.
AB  - BACKGROUND: Cells permissive to virus can become refractory to viral replication
      upon intracellular expression of single chain fragment variable (scFv) antibodies
      directed towards viral structural or regulatory proteins, or virus-coded enzymes.
      For example, an intrabody derived from MH-SVM33, a monoclonal antibody against a
      conserved C-terminal epitope of the HIV-1 matrix protein (MAp17), was found to
      exert an inhibitory effect on HIV-1 replication. RESULTS: Two versions of MH
      SVM33-derived scFv were constructed in recombinant baculoviruses (BVs) and
      expressed in BV-infected Sf9 cells, N-myristoylation-competent scFvG2/p17 and N
      myristoylation-incompetent scFvE2/p17 protein, both carrying a C-terminal HA tag.
      ScFvG2/p17 expression resulted in an insoluble, membrane-associated protein,
      whereas scFvE2/p17 was recovered in both soluble and membrane-incorporated forms.
      When coexpressed with the HIV-1 Pr55Gag precursor, scFvG2/p17 and scFvE2/p17 did
      not show any detectable negative effect on virus-like particle (VLP) assembly and
      egress, and both failed to be encapsidated in VLP. However, soluble scFvE2/p17
      isolated from Sf9 cell lysates was capable of binding to its specific antigen, in
      the form of a synthetic p17 peptide or as Gag polyprotein-embedded epitope.
      Significant amounts of scFvE2/p17 were released in the extracellular medium of BV
      infected cells in high-molecular weight, pelletable form. This particulate form
      corresponded to BV particles displaying scFvE2/p17 molecules, inserted into the
      BV envelope via the scFv N-terminal region. The BV-displayed scFvE2/p17 molecules
      were found to be immunologically functional, as they reacted with the C-terminal
      epitope of MAp17. Fusion of the N-terminal 18 amino acid residues from the
      scFvE2/p17 sequence (N18E2) to another scFv recognizing CD147 (scFv-M6-1B9)
      conferred the property of BV-display to the resulting chimeric scFv-N18E2/M6.
      CONCLUSION: Expression of scFvE2/p17 in insect cells using a BV vector resulted
      in baculoviral progeny displaying scFvE2/p17. The function required for BV
      envelope incorporation was carried by the N-terminal octadecapeptide of
      scFvE2/p17, which acted as a signal peptide for BV display. Fusion of this
      peptide to the N-terminus of scFv molecules of interest could be applied as a
      general method for BV-display of scFv in a GP64- and VSV-G-independent manner.

PMID- 21092084
TI  - Evidence of inhibin/activin subunit betaC and betaE synthesis in normal human
      endometrial tissue.
AB  - BACKGROUND: Inhibins are important regulators of the female reproductive system.
      Recently, two new inhibin subunits betaC and betaE have been described, although
      it is unclear if they are synthesized in normal human endometrium. METHODS:
      Samples of human endometrium were obtained from 82 premenopausal, non-pregnant
      patients undergoing gynecological surgery for benign diseases. Endometrium
      samples were classified according to anamnestic and histological dating into
      proliferative (day 1-14, n = 46), early secretory (day 15-22, n = 18) and late
      secretory phase (day 23-28, n = 18). Immunohistochemical analyses were performed
      with specific antibodies against inhibin alpha (n = 81) as well as inhibin betaA
      (n = 82), betaB (n = 82), betaC (n = 74) and betaE (n = 76) subunits. RT-PCR was
      performed for all inhibin subunits. Correlation was assessed with the Spearman
      factor to assess the relationship of inhibin-subunits expression within the
      different endometrial samples. RESULTS: The novel inhibin betaC and betaE
      subunits were found in normal human endometrium by immunohistochemical and
      molecular techniques. Inhibin alpha, betaA, betaB and betaE subunits showed a
      circadian expression pattern, being more abundant during the late secretory phase
      than during the proliferative phase. Additionally, a significant correlation
      between inhibin alpha and all inhibin beta subunits was observed. CONCLUSIONS:
      The differential expression pattern of the betaC- and betaE-subunits in normal
      human endometrial tissue suggests that they function in endometrial maturation
      and blastocyst implantation. However, the precise role of these novel
      inhibin/activin subunits in human endometrium is unclear and warrants further
      investigation.

PMID- 21092085
TI  - "Bong lung" in cystic fibrosis: a case report.
AB  - INTRODUCTION: Marijuana or "bong" lung has been recently described. Subjects
      typically develop large peripheral paraseptal lung bullae and are predisposed to
      spontaneous pneumothoraces. The underlying mechanism for bullae formation is
      uncertain, but probably relates to direct lung toxicity and repeated barotrauma
      as the smoker performs frequent valsalva manoeuvres in an attempt to derive a
      greater drug effect. CASE PRESENTATION: We describe a case of probable "bong
      lung" occurring in a 23-year-old Caucasian man with cystic fibrosis who had a
      history of recurrent pneumothoraces and unusual findings on sputum cytology.
      CONCLUSION: Our case highlights the importance of questioning young adult cystic
      fibrosis patients about illicit drug use and the utility of sputum cytology and
      computed tomography scanning when patients present with pneumothoraces and
      deteriorations in clinical status.

PMID- 21092086
TI  - Living donor liver transplantation for neonatal hemochromatosis using non
      anatomically resected segments II and III: a case report.
AB  - INTRODUCTION: Neonatal hemochromatosis is the most common cause of liver failure
      and liver transplantation in the newborn. The size of the infant determines the
      liver volume that can be transplanted safely without incurring complications
      arising from a large graft. Transplantation of monosegments II or III is a
      standard method for the newborns with liver failure. CASE PRESENTATION: A three
      week old African-American male neonate was diagnosed with acute liver failure
      secondary to neonatal hemochromatosis. Living-related liver transplantation was
      considered after the failure of intensive medical therapy. Intra-operatively a
      non-anatomical resection and transplantation of segments II and III was performed
      successfully. The boy is growing normally two years after the transplantation.
      CONCLUSION: Non-anatomical resection and transplantation of liver segments II and
      III is preferred to the transplantation of anatomically resected monosegements,
      especially when the left lobe is thin and flat. It allows the use of a reduced
      size donor liver with intact hilar structures and outflow veins. In an emergency,
      living-related liver transplantation should be offered to infants with liver
      failure secondary to neonatal hemochromatosis who fail to respond to medical
      treatment.

PMID- 21092087
TI  - Use of rifampin in persistent coagulase negative staphylococcal bacteremia in
      neonates.
AB  - BACKGROUND: Coagulase negative staphylococci (CoNS) are the most common cause of
      neonatal sepsis in the Neonatal Intensive Care Unit (NICU). A minority of
      neonates does not respond to vancomycin therapy and develops persistent
      bacteremia, which may be treated with rifampin. We evaluated the use of rifampin
      in persistent CoNS bacteremia. METHODS: Retrospective study of 137 neonates with
      CoNS bacteremia during admission to a tertiary NICU between July 2006 and July
      2009. Main outcome measures were total duration of bacteremia and the adequacy of
      vancomycin and rifampin therapy. RESULTS: 137/1696 (8.0%) neonates developed a
      CoNS bacteremia. Eighteen were treated with rifampin because of persistent
      bacteremia (3 positive blood cultures at least 48 hours apart with clinical
      symptoms) or (a serious suspicion of) an intravascular thrombus. Duration of
      bacteremia prior to rifampin therapy (8.0 +/- 3.6 days) was positively correlated
      (p < 0.001) to the total duration of bacteremia (10.3 +/- 3.7 days). After
      starting rifampin therapy C-reactive protein (CRP) levels of all neonates
      declined and blood cultures became sterile after 2.3 +/- 1.6 days. Vancomycin
      levels were not consistently measured in all neonates, resulting in late
      detection of subtherapeutic trough levels. CONCLUSION: Rifampin may be effective
      in the treatment of persistent CoNS infections in neonates. Outcome may be
      improved by adequate monitoring of vancomycin trough levels.

PMID- 21092088
TI  - Initiating undergraduate medical students into communities of research practise:
      what do supervisors recommend?
AB  - BACKGROUND: Much has been written in the educational literature on the value of
      communities of practise in enhancing student learning. Here, we take the
      experience of senior undergraduate medical students involved in short-term
      research as a member of a team as a paradigm for learning in a community of
      practise. Based on feedback from experienced supervisors, we offer
      recommendations for initiating students into the research culture of their team.
      In so doing, we endeavour to create a bridge between theory and practise through
      disseminating advice on good supervisory practise, where the supervisor is
      perceived as an educator responsible for designing the research process to
      optimize student learning. METHODS: Using the questionnaire design tool
      SurveyMonkey and comprehensive lists of contact details of staff who had
      supervised research projects at the University of Edinburgh during 1995-2008,
      current and previous supervisors were invited to recommend procedures which they
      had found successful in initiating students into the research culture of a team.
      Text responses were then coded in the form of derivative recommendations and
      categorized under general themes and sub-themes. RESULTS: Using the chi-square
      tests of linear trend and association, evidence was found for a positive trend
      towards more experienced supervisors offering responses (chi2 = 16.833, p <
      0.0005, n = 215) while there was a lack of evidence of bias in the gender
      distribution of respondents (chi2 = 0.482, p = 0.487, n = 203), respectively. A
      total of 126 codes were extracted from the text responses of 65 respondents.
      These codes were simplified to form a complete list of 52 recommendations, which
      were in turn categorized under seven derivative overarching themes, the most
      highly represented themes being Connecting the student with others and
      Cultivating self-efficacy in research competence. CONCLUSIONS: Through the design
      of a coding frame for supervisor responses, a wealth of ideas has been captured
      to make communities of research practise effective mediums for undergraduate
      student learning. The majority of these recommendations are underpinned by
      educational theory and have the potential to take the learner beyond the stage of
      initiation to that of integration within their community of research practise.

PMID- 21092089
TI  - Interaction between drug and placebo effects: a cross-over balanced placebo
      design trial.
AB  - BACKGROUND: The total effect of a medication is the sum of its drug effect,
      placebo effect (meaning response), and their possible interaction. Current
      interpretation of clinical trials' results assumes no interaction. Demonstrating
      such an interaction has been difficult due to lack of an appropriate study
      design. METHODS: 180 adults were randomized to caffeine (300 mg) or placebo
      groups. Each group received the assigned intervention described by the
      investigators as caffeine or placebo, in a randomized crossover design. 4-hour
      area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog
      scales), and systolic blood pressure levels as well as caffeine pharmacokinetics
      (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug,
      placebo, placebo-plus-interaction, and total effects were estimated by comparing
      outcomes after, receiving caffeine described as placebo to receiving placebo
      described as placebo, receiving placebo described as caffeine or placebo,
      receiving caffeine described as caffeine or placebo, and receiving caffeine
      described as caffeine to receiving placebo described as placebo, respectively.
      RESULTS: The placebo effect on area-under-the-curve of energy (mean difference)
      and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction
      effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to
      0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect
      (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its
      combination with the later was larger than total caffeine effect (29.5 [11.9 to
      47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased
      caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P=0.007). CONCLUSIONS:
      Drug and placebo effects of a medication may be less than additive, which
      influences the interpretation of clinical trials. The placebo effect may increase
      active drug terminal half-life, a novel mechanism of placebo action. TRIAL
      REGISTRATION: ClinicalTrials.gov identification number - NCT00426010.

PMID- 21092090
TI  - Doing masculinity, not doing health? A qualitative study among Dutch male
      employees about health beliefs and workplace physical activity.
AB  - BACKGROUND: Being female is a strong predictor of health promoting behaviours.
      Workplaces show great potential for lifestyle interventions, but such
      interventions do not necessarily take the gendered background of lifestyle
      behaviours into account. A perspective analyzing how masculine gender norms
      affect health promoting behaviours is important. This study aims to explore men's
      health beliefs and attitudes towards health promotion; in particular, it explores
      workplace physical activity in relation to masculine ideals among male employees.
      METHODS: In the Fall of 2008, we interviewed 13 white Dutch male employees aged
      23-56 years. The men worked in a wide range of professions and occupational
      sectors and all interviewees had been offered a workplace physical activity
      program. Interviews lasted approximately one to one-and-a-half hour and addressed
      beliefs about health and lifestyle behaviours including workplace physical
      activity, as well as normative beliefs about masculinity. Thematic analysis was
      used to analyze the data. RESULTS: Two normative themes were found: first, the
      ideal man is equated with being a winner and real men are prepared to compete,
      and second, real men are not whiners and ideally, not vulnerable. Workplace
      physical activity is associated with a particular type of masculinity - young,
      occupied with looks, and interested in muscle building. Masculine norms are
      related to challenging health while taking care of health is feminine and, hence,
      something to avoid. Workplace physical activity is not framed as a health
      measure, and not mentioned as of importance to the work role. CONCLUSIONS:
      Competitiveness and nonchalant attitudes towards health shape masculine ideals.
      In regards to workplace physical activity, some men resist what they perceive to
      be an emphasis on muscled looks, whereas for others it contributes to looking
      self-confident. In order to establish a greater reach among vulnerable employees
      such as ageing men, worksite health promotion programs including workplace
      physical activity may benefit from greater insight in the tensions between health
      behaviours and masculinity.

PMID- 21092091
TI  - A rare cause of chronic mesenteric ischemia from fibromuscular dysplasia: a case
      report.
AB  - INTRODUCTION: Chronic mesenteric ischemia is a condition that is classically
      associated with significant atherosclerosis of the abdominal arteries, causing
      postprandial abdominal pain out of proportion to physical examination. The
      abdominal pain is exacerbated after meals due to the shunting of blood away from
      the intestines to the stomach, causing relative ischemia. More than 95% of
      chronic mesenteric ischemia cases are due to atherosclerosis. We report the first
      known case of chronic mesenteric ischemia from fibromuscular dysplasia. To the
      best of our knowledge, this is also the first known case in the literature where
      postprandial abdominal pain was the presenting symptom of fibromuscular
      dysplasia. CASE PRESENTATION: A 44-year-old Caucasian woman with a history of
      hypertension and preeclampsia, who had taken oral contraceptive pills for 15
      years, presented with an intractable, colicky abdominal pain of two weeks
      duration. This abdominal pain worsened with oral intake. It was also associated
      with diarrhea and vomiting. Physical examination revealed stage III hypertension
      out of proportion to her risk factors and diffuse abdominal pain without
      peritoneal signs. An abdominal computed tomography scan, completed in the
      emergency room, revealed nonspecific colitis. Laboratory work revealed
      leukocytosis with a left shift, an erythrocyte sedimentation rate of 79 and a C
      reactive protein level of 100. She was started on intravenous flagyl and
      intravenous ciprofloxacin. However, all microbial cultures were negative
      including three cultures for clostridium difficile. Urine analysis revealed
      nephritic range proteinuria. The laboratory profile was within normal limits for
      perinuclear-anti-neutrophil cytoplasmic antibody, cytoplasmic-anti-neutrophil
      cytoplasmic antibody, anti-saccharomyces cerevisiae antibody, antinuclear
      antibody test, celiac profile, lactate, carbohydrate antigen-125 and thyroid
      stimulating hormone. A colonoscopy was completed, which revealed diffuse colonic
      lymphoid reactive hyperplasia. A small bowel series was negative for any
      inflammation. An indium scan, pan-computed tomography scan and transvaginal
      ultrasound were also negative. Magnetic resonance angiography of her abdomen
      revealed proximal superior mesenteric artery stenosis, which was confirmed by
      computed tomography angiogram findings of severe proximal and distal superior
      mesenteric artery stenosis, consistent with the appearance of fibromuscular
      dysplasia on angiography in the absence of vasculitis or atherosclerotic disease.
      The patient's superior mesenteric artery stenosis was subsequently angioplastied
      suboptimally and had to be stented with an Angioplus stent. One month after she
      was admitted, her abdominal pain and tolerance to oral feeds improved
      tremendously. CONCLUSION: Fibromuscular dysplasia most commonly presents with
      renal artery stenosis, which rarely causes abdominal pain. This case illustrates
      how fibromuscular dysplasia can present as a rare cause of chronic mesenteric
      ischemia, similar to chronic mesenteric ischemia from atherosclerosis.

PMID- 21092092
TI  - Enabling access to new WHO essential medicines: the case for nicotine replacement
      therapies.
AB  - Nicotine replacement therapies (NRT) are powerful tools for the successful
      treatment of nicotine addiction and tobacco use. The medicines are clinically
      effective, supported by the Framework Convention on Tobacco Control, and are now
      World Health Organization-approved essential medicines. Enabling global access to
      NRT remains a challenge given ongoing confusion and misperceptions about their
      efficacy, cost-effectiveness, and availability with respect to other tobacco
      control and public health opportunities. In this commentary, we review existing
      evidence and guidelines to make the case for global access to NRT highlighting
      the smoker's right to access treatment to sensibly address nicotine addiction.

PMID- 21092093
TI  - Associations of alcohol consumption with diabetes mellitus and impaired fasting
      glycemia among middle-aged and elderly Chinese.
AB  - BACKGROUND: The U-shaped relationship between alcohol consumption and diabetes
      mellitus was observed among western populations. However, few studies have
      systematically evaluated the association in Chinese. We aimed to investigate the
      associations of alcohol consumption with diabetes mellitus and impaired fasting
      glycemia (IFG) among middle-aged and elderly Chinese. METHODS: We examined 1,458
      men and 1,831 women aged 50 to 70 from Beijing and Shanghai China in a cross
      sectional survey. Fasting glucose, adipokines and markers of inflammation were
      measured. Macronutrients and alcohol consumption were assessed with standardized
      questionnaires. RESULTS: Compared with abstainers, alcohol consumption was
      associated with a decreased risk of having diabetes mellitus in women (OR: 0.41,
      95%CI: 0.22-0.78) after controlling for socio-demographic factors, physical
      activity, smoking, family income, family history of cardiovascular disease or
      diabetes, macronutrients intake, body mass index, and markers of inflammation and
      adipokines. In men, both low and high alcohol consumptions were associated with
      increased risks of having combined diabetes and IFG (ORs 1.36 [95%CI: 1.02-1.82]
      and 1.50 [95%CI: 1.04-2.15], respectively]. In the multivariable stratified
      analyses among men, moderate drinkers who had drinking days of >= 5 days/week had
      a deceased likelihood (OR: 0.61, 95%CI: 0.37-0.98) and liquor drinkers had an
      increased likelihood (OR: 1.47, 95%CI: 1.09-1.98) of having combined diabetes and
      IFG respectively, compared with the abstainers. CONCLUSIONS: An approximately J
      shaped association was observed between alcohol consumption and combined diabetes
      and IFG among men compared with abstainers in Chinese. Whether moderate alcohol
      intake could help decrease diabetic risk among Chinese people warrants further
      investigation.

PMID- 21092094
TI  - Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28,
      cause increased phenotypic noise.
AB  - BACKGROUND: Inbred individuals reared in controlled environments display
      considerable variance in many complex traits but the underlying cause of this
      intangible variation has been an enigma. Here we show that two modifiers of
      epigenetic gene silencing play a critical role in the process. RESULTS: Inbred
      mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or
      tripartite motif protein 28 (Trim28) show greater coefficients of variance in
      body weight than their wild-type littermates. Trim28 mutants additionally develop
      metabolic syndrome and abnormal behavior with incomplete penetrance. Genome-wide
      gene expression analyses identified 284 significantly dysregulated genes in
      Trim28 heterozygote mutants compared to wild-type mice, with Mas1, which encodes
      a G-protein coupled receptor implicated in lipid metabolism, showing the greatest
      average change in expression (7.8-fold higher in mutants). This gene also showed
      highly variable expression between mutant individuals. CONCLUSIONS: These studies
      provide a molecular explanation of developmental noise in whole organisms and
      suggest that faithful epigenetic control of transcription is central to
      suppressing deleterious levels of phenotypic variation. These findings have broad
      implications for understanding the mechanisms underlying sporadic and complex
      disease in humans.

PMID- 21092095
TI  - Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical
      myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold.
AB  - BACKGROUND: T1 mapping allows direct in-vivo quantitation of microscopic changes
      in the myocardium, providing new diagnostic insights into cardiac disease.
      Existing methods require long breath holds that are demanding for many cardiac
      patients. In this work we propose and validate a novel, clinically applicable,
      pulse sequence for myocardial T1-mapping that is compatible with typical limits
      for end-expiration breath-holding in patients. MATERIALS AND METHODS: The
      Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses
      sequential inversion recovery measurements within a single short breath-hold.
      Full recovery of the longitudinal magnetisation between sequential inversion
      pulses is not achieved, but conditional interpretation of samples for
      reconstruction of T1-maps is used to yield accurate measurements, and this
      algorithm is implemented directly on the scanner. We performed computer
      simulations for 100 ms<T1 < 2.7 s and heart rates 40-100 bpm followed by phantom
      validation at 1.5T and 3T. In-vivo myocardial T1-mapping using this method and
      the previous gold-standard (MOLLI) was performed in 10 healthy volunteers at 1.5T
      and 3T, 4 volunteers with contrast injection at 1.5T, and 4 patients with recent
      myocardial infarction (MI) at 3T. RESULTS: We found good agreement between the
      average ShMOLLI and MOLLI estimates for T1 < 1200 ms. In contrast to the original
      method, ShMOLLI showed no dependence on heart rates for long T1 values, with
      estimates characterized by a constant 4% underestimation for T1 = 800-2700 ms. In
      vivo, ShMOLLI measurements required 9.0 +/- 1.1 s (MOLLI = 17.6 +/- 2.9 s).
      Average healthy myocardial T1 s by ShMOLLI at 1.5T were 966 +/- 48 ms (mean +/-
      SD) and 1166 +/- 60 ms at 3T. In MI patients, the T1 in unaffected myocardium
      (1216 +/- 42 ms) was similar to controls at 3T. Ischemically injured myocardium
      showed increased T1 = 1432 +/- 33 ms (p < 0.001). The difference between MI and
      remote myocardium was estimated 15% larger by ShMOLLI than MOLLI (p < 0.04) which
      suffers from heart rate dependencies for long T1. The in-vivo variability within
      ShMOLLI T1-maps was only 14% (1.5T) or 18% (3T) higher than the MOLLI maps, but
      the MOLLI acquisitions were twice longer than ShMOLLI acquisitions. CONCLUSION:
      ShMOLLI is an efficient method that generates immediate, high-resolution
      myocardial T1-maps in a short breath-hold with high precision. This technique
      provides a valuable clinically applicable tool for myocardial tissue
      characterisation.

PMID- 21092096
TI  - Modeling and simulation of the main metabolism in Escherichia coli and its
      several single-gene knockout mutants with experimental verification.
AB  - BACKGROUND: It is quite important to simulate the metabolic changes of a cell in
      response to the change in culture environment and/or specific gene knockouts
      particularly for the purpose of application in industry. If this could be done,
      the cell design can be made without conducting exhaustive experiments, and one
      can screen out the promising candidates, proceeded by experimental verification
      of a select few of particular interest. Although several models have so far been
      proposed, most of them focus on the specific metabolic pathways. It is preferred
      to model the whole of the main metabolic pathways in Escherichia coli, allowing
      for the estimation of energy generation and cell synthesis, based on
      intracellular fluxes and that may be used to characterize phenotypic growth.
      RESULTS: In the present study, we considered the simulation of the main metabolic
      pathways such as glycolysis, TCA cycle, pentose phosphate (PP) pathway, and the
      anapleorotic pathways using enzymatic reaction models of E. coli. Once
      intracellular fluxes were computed by this model, the specific ATP production
      rate, the specific CO2 production rate, and the specific NADPH production rate
      could be estimated. The specific ATP production rate thus computed was used for
      the estimation of the specific growth rate. The CO2 production rate could be used
      to estimate cell yield, and the specific NADPH production rate could be used to
      determine the flux of the oxidative PP pathway. The batch and continuous
      cultivations were simulated where the changing patterns of extracellular and
      intra-cellular metabolite concentrations were compared with experimental data.
      Moreover, the effects of the knockout of such pathways as Ppc, Pck and Pyk on the
      metabolism were simulated. It was shown to be difficult for the cell to grow in
      Ppc mutant due to low concentration of OAA, while Pck mutant does not necessarily
      show this phenomenon. The slower growth rate of the Ppc mutant was properly
      estimated by taking into account the lower specific ATP production rate. In the
      case of Pyk mutant, the enzyme level regulation was made clear such that Pyk
      knockout caused PEP concentration to be up-regulated and activated Ppc, which
      caused the increase in MAL concentration and backed up reduced PYR through Mez,
      resulting in the phenotypic growth characteristics similar to the wild type.
      CONCLUSIONS: It was shown to be useful to simulate the main metabolism of E. coli
      for understanding metabolic changes inside the cell in response to specific
      pathway gene knockouts, considering the whole main metabolic pathways. The
      comparison of the simulation result with the experimental data indicates that the
      present model could simulate the effect of the specific gene knockouts to the
      changes in the metabolisms to some extent.

PMID- 21092097
TI  - Molecular epidemiology of Plasmodium species prevalent in Yemen based on 18 s
      rRNA.
AB  - BACKGROUND: Malaria is an endemic disease in Yemen and is responsible for 4.9
      deaths per 100,000 population per year and 43,000 disability adjusted life years
      lost. Although malaria in Yemen is caused mainly by Plasmodium falciparum and
      Plasmodium vivax, there are no sequence data available on the two species. This
      study was conducted to investigate the distribution of the Plasmodium species
      based on the molecular detection and to study the molecular phylogeny of these
      parasites. METHODS: Blood samples from 511 febrile patients were collected and a
      partial region of the 18 s ribosomal RNA (18 s rRNA) gene was amplified using
      nested PCR. From the 86 positive blood samples, 13 Plasmodium falciparum and 4
      Plasmodium vivax were selected and underwent cloning and, subsequently,
      sequencing and the sequences were subjected to phylogenetic analysis using the
      neighbor-joining and maximum parsimony methods. RESULTS: Malaria was detected by
      PCR in 86 samples (16.8%). The majority of the single infections were caused by
      P. falciparum (80.3%), followed by P. vivax (5.8%). Mixed infection rates of P.
      falciparum + P. vivax and P. falciparum + P. malariae were 11.6% and 2.3%,
      respectively. All P. falciparum isolates were grouped with the strain 3D7, while
      P. vivax isolates were grouped with the strain Salvador1. Phylogenetic trees
      based on 18 s rRNA placed the P. falciparum isolates into three sub-clusters and
      P. vivax into one cluster. Sequence alignment analysis showed 5-14.8% SNP in the
      partial sequences of the 18 s rRNA of P. falciparum. CONCLUSIONS: Although P.
      falciparum is predominant, P. vivax, P. malariae and mixed infections are more
      prevalent than has been revealed by microscopy. This overlooked distribution
      should be considered by malaria control strategy makers. The genetic
      polymorphisms warrant further investigation.

PMID- 21092099
TI  - Sharing clinical research data in the United States under the Health Insurance
      Portability and Accountability Act and the Privacy Rule.
AB  - Sharing of final research data from clinical research is an essential part of the
      scientific method. The U.S. National Institutes of Health require some grant
      applications to include plans for sharing final research data, which it defines
      as the factual materials necessary to document, support, and validate research
      findings. In the U.S., however, the Privacy Rule adopted under the Health
      Insurance Portability and Accountability Act impedes the sharing of final
      research data. In most situations, final research data may be shared only where
      all information that could possibly be used to identify the subject has been
      deleted, or where the subject has given authorization for specific research, or
      an Institutional Review Board has granted a waiver.

PMID- 21092098
TI  - The impact of care pathways for exacerbation of Chronic Obstructive Pulmonary
      Disease: rationale and design of a cluster randomized controlled trial.
AB  - BACKGROUND: Hospital treatment of chronic obstructive pulmonary disease (COPD)
      frequently does not follow published evidences. This lack of adherence can
      contribute to the high morbidity, mortality and readmissions rates. The European
      Quality of Care Pathway (EQCP) study on acute exacerbations of COPD (NTC00962468)
      is undertaken to determine how care pathways (CP) as complex intervention for
      hospital treatment of COPD affects care variability, adherence to evidence based
      key interventions and clinical outcomes. METHODS: An international cluster
      Randomized Controlled Trial (cRCT) will be performed in Belgium, Italy, Ireland
      and Portugal. Based on the power analysis, a sample of 40 hospital teams and 398
      patients will be included in the study. In the control arm of the study, usual
      care will be provided. The experimental teams will implement a CP as complex
      intervention which will include three active components: a formative evaluation
      of the quality and organization of care, a set of evidence based key
      interventions, and support on the development and implementation of the CP. The
      main outcome will be six-month readmission rate. As a secondary endpoint a set of
      clinical outcome and performance indicators (including care process evaluation
      and team functioning indicators) will be measured in both groups. DISCUSSION: The
      EQCP study is the first international cRCT on care pathways. The design of the
      EQCP project is both a research study and a quality improvement project and will
      include a realistic evaluation framework including process analysis to further
      understand why and when CP can really work. TRIAL REGISTRATION NUMBER:
      NCT00962468.

PMID- 21092100
TI  - Pregabalin, the lidocaine plaster and duloxetine in patients with refractory
      neuropathic pain: a systematic review.
AB  - BACKGROUND: Patients frequently fail to receive adequate pain relief from, or are
      intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This
      refractory chronic pain causes psychological distress and impacts patient quality
      of life. Published literature for treatment in refractory patients is sparse and
      often published as conference abstracts only. The aim of this study was to
      identify published data for three pharmacological treatments: pregabalin,
      lidocaine plaster, and duloxetine, which are typically used at 2(nd) line or
      later in UK patients with neuropathic pain. METHODS: A systematic review of the
      literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented
      with extensive conference and grey literature searching. Studies of any design
      (except single patient case studies) that enrolled adult patients with refractory
      NeP were included in the review and qualitatively assessed. RESULTS: Seventeen
      studies were included in the review: nine of pregabalin, seven of the lidocaine
      plaster, and one of duloxetine. No head-to-head studies of these treatments were
      identified. Only six studies included treatments within UK licensed indications
      and dose ranges. Reported efficacy outcomes were not consistent between studies.
      Pain scores were most commonly assessed in studies including pregabalin; trials
      of pregabalin and the lidocaine plaster reported the proportion of responders.
      Significant improvements in the total, sensory and affective scores of the Short
      form McGill Pain Questionnaire, and in function interference, sleep interference
      and pain associated distress, were associated with pregabalin treatment; limited
      or no quality of life data were available for the other two interventions.
      Limitations to the review are the small number of included studies, which are
      generally small, of poor quality and heterogeneous in patient population and
      study design. CONCLUSIONS: Little evidence is available relevant to the treatment
      of refractory neuropathic pain despite the clinical need. There is a notable lack
      of high-quality comparative studies. It is evident that there is a need for
      future, high quality trials, particularly "gold-standard" RCTs in this refractory
      patient population.

PMID- 21092101
TI  - A genetic network model of cellular responses to lithium treatment and cocaine
      abuse in bipolar disorder.
AB  - BACKGROUND: Lithium is an effective treatment for Bipolar Disorder (BD) and
      significantly reduces suicide risk, though the molecular basis of lithium's
      effectiveness is not well understood. We seek to improve our understanding of
      this effectiveness by posing hypotheses based on new experimental data as well as
      published data, testing these hypotheses in silico, and posing new hypotheses for
      validation in future studies. We initially hypothesized a gene-by-environment
      interaction where lithium, acting as an environmental influence, impacts signal
      transduction pathways leading to differential expression of genes important in
      the etiology of BD mania. RESULTS: Using microarray and rt-QPCR assays, we
      identified candidate genes that are differentially expressed with lithium
      treatment. We used a systems biology approach to identify interactions among
      these candidate genes and develop a network of genes that interact with the
      differentially expressed candidates. Notably, we also identified cocaine as
      having a potential influence on the network, consistent with the observed high
      rate of comorbidity for BD and cocaine abuse. The resulting network represents a
      novel hypothesis on how multiple genetic influences on bipolar disorder are
      impacted by both lithium treatment and cocaine use. Testing this network for
      association with BD and related phenotypes, we find that it is significantly over
      represented for genes that participate in signal transduction, consistent with
      our hypothesized-gene-by environment interaction. In addition, it models related
      pharmacogenomic, psychiatric, and chemical dependence phenotypes. CONCLUSIONS: We
      offer a network model of gene-by-environment interaction associated with
      lithium's effectiveness in treating BD mania, as well as the observed high rate
      of comorbidity of BD and cocaine abuse. We identified drug targets within this
      network that represent immediate candidates for therapeutic drug testing. Posing
      novel hypotheses for validation in future work, we prioritized SNPs near genes in
      the network based on functional annotation. We also developed a "concept
      signature" for the genes in the network and identified additional candidate genes
      that may influence the system because they are significantly associated with the
      signature.

PMID- 21092102
TI  - Translational independence between overlapping genes for a restriction
      endonuclease and its transcriptional regulator.
AB  - BACKGROUND: Most type II restriction-modification (RM) systems have two
      independent enzymes that act on the same DNA sequence: a modification
      methyltransferase that protects target sites, and a restriction endonuclease that
      cleaves unmethylated target sites. When RM genes enter a new cell, methylation
      must occur before restriction activity appears, or the host's chromosome is
      digested. Transcriptional mechanisms that delay endonuclease expression have been
      identified in some RM systems. A substantial subset of those systems is
      controlled by a family of small transcription activators called C proteins. In
      the PvuII system, C.PvuII activates transcription of its own gene, along with
      that of the downstream endonuclease gene. This regulation results in very low
      R.PvuII mRNA levels early after gene entry, followed by rapid increase due to
      positive feedback. However, given the lethal consequences of premature REase
      accumulation, transcriptional control alone might be insufficient. In C
      controlled RM systems, there is a +/- 20 nt overlap between the C termination
      codon and the R (endonuclease) initiation codon, suggesting possible
      translational coupling, and in many cases predicted RNA hairpins could occlude
      the ribosome binding site for the endonuclease gene. RESULTS: Expression levels
      of lacZ translational fusions to pvuIIR or pvuIIC were determined, with the
      native pvuII promoter having been replaced by one not controlled by C.PvuII. In
      frame pvuIIC insertions did not substantially decrease either pvuIIC-lacZ or
      pvuIIR-lacZ expression (with or without C.PvuII provided in trans). In contrast,
      a frameshift mutation in pvuIIC decreased expression markedly in both fusions,
      but mRNA measurements indicated that this decrease could be explained by
      transcriptional polarity. Expression of pvuIIR-lacZ was unaffected when the
      pvuIIC stop codon was moved 21 nt downstream from its WT location, or 25 or 40 bp
      upstream of the pvuIIR initiation codon. Disrupting the putative hairpins had no
      significant effects. CONCLUSIONS: The initiation of translation of pvuIIR appears
      to be independent of that for pvuIIC. Direct tests failed to detect regulatory
      rules for either gene overlap or the putative hairpins. Thus, at least during
      balanced growth, transcriptional control appears to be sufficiently robust for
      proper regulation of this RM system.

PMID- 21092103
TI  - Phylogenetic relationships in genus Arachis based on ITS and 5.8S rDNA sequences.
AB  - BACKGROUND: The genus Arachis comprises 80 species and it is subdivided into nine
      taxonomic sections (Arachis, Caulorrhizae, Erectoides, Extranervosae,
      Heteranthae, Procumbentes, Rhizomatosae, Trierectoides, and Triseminatae). This
      genus is naturally confined to South America and most of its species are native
      to Brazil. In order to provide a better understanding of the evolution of the
      genus, we reconstructed the phylogeny of 45 species using the variation observed
      on nucleotide sequences in internal transcribed spacer regions (ITS1 and ITS2)
      and 5.8 S of nuclear ribosomal DNA. RESULTS: Intraspecific variation was
      detected, but in general it was not enough to place accessions of the same
      species in different clades. Our data support the view that Arachis is a
      monophyletic group and suggested Heteranthae as the most primitive section of
      genus Arachis. The results confirmed the circumscriptions of some sections
      (Caulorrhizae, Extranervosae), but raised questions about others. Sections
      Erectoides, Trierectoides and Procumbentes were not well defined, while sections
      Arachis and Rhizomatosae seem to include species that could be moved to different
      sections. The division of section Arachis into A and B genome species was also
      observed in the phylogenetic tree and these two groups of species may not have a
      monophyletic origin. The 2n = 2x = 18 species of section Arachis (A. praecox, A.
      palustris and A. decora) were all placed in the same clade, indicating they are
      closely related to each other, and their genomes are more related to B genome
      than to the A genome. Data also allowed insights on the origin of tetraploid A.
      glabrata, suggesting rhizome appeared twice within the genus and raising
      questions about the placement of that species in section Rhizomatosae.
      CONCLUSION: The main clades established in this study in general agreed with many
      other studies that have used other types of evidences and sets of species, being
      some of them included in our study and some not. Thus, the relationships
      established can be a useful framework for future systematic reviews of genus
      Arachis and for the selection of species to pre-breeding programs.

PMID- 21092104
TI  - Type D personality is associated with increased metabolic syndrome prevalence and
      an unhealthy lifestyle in a cross-sectional Dutch community sample.
AB  - BACKGROUND: People with Type D-Distressed-personality have a general tendency
      towards increased negative affectivity (NA), while at the same time inhibiting
      these emotions in social situations (SI). Type D personality is associated with
      an increased risk of adverse outcomes in patients with cardiovascular disease.
      Whether Type D personality is a cardiovascular risk factor in healthy populations
      remains to be investigated. In the present study, the relations between Type D
      personality and classical cardiovascular risk factors, i.e. metabolic syndrome
      and lifestyle were investigated in a Dutch community sample. METHODS: In a cross
      sectional study 1592 participants were included, aged 20-80 years. Metabolic
      syndrome was defined by self-report, following the International Diabetes
      Federation-IDF-guidelines including an increased waist circumference,
      dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking,
      alcohol use, exercise and dietary habits were examined. Metabolic syndrome
      prevalence was stratified by Type D personality (a high score on both NA and SI),
      lifestyle and confounders age, gender, having a partner, higher education level,
      cardiac history, family history of cardiovascular disease. RESULTS: Metabolic
      syndrome was more prevalent in persons with a Type D personality (13% vs. 6%).
      Persons with Type D personality made poorer lifestyle choices, adhered less to
      the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, p = .02), had a less
      varied diet (OR = 0.50, 95%CI = 0.40-0.70, p < .0005), and were less likely to
      restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, p = .01). Type D
      personality was related to a twofold increased risk of metabolic syndrome (OR =
      2.2, 95%CI = 1.2-4.0, p = .011), independent of lifestyle factors and
      confounders. CONCLUSIONS: Type D personality is related to an increased
      prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both
      behavioral and biological vulnerability for development of cardiovascular
      disorders and diabetes.

PMID- 21092105
TI  - Bovine Genome Database: supporting community annotation and analysis of the Bos
      taurus genome.
AB  - BACKGROUND: A goal of the Bovine Genome Database (BGD; http://BovineGenome.org)
      has been to support the Bovine Genome Sequencing and Analysis Consortium (BGSAC)
      in the annotation and analysis of the bovine genome. We were faced with several
      challenges, including the need to maintain consistent quality despite diversity
      in annotation expertise in the research community, the need to maintain
      consistent data formats, and the need to minimize the potential duplication of
      annotation effort. With new sequencing technologies allowing many more eukaryotic
      genomes to be sequenced, the demand for collaborative annotation is likely to
      increase. Here we present our approach, challenges and solutions facilitating a
      large distributed annotation project. RESULTS AND DISCUSSION: BGD has provided
      annotation tools that supported 147 members of the BGSAC in contributing 3,871
      gene models over a fifteen-week period, and these annotations have been
      integrated into the bovine Official Gene Set. Our approach has been to provide an
      annotation system, which includes a BLAST site, multiple genome browsers, an
      annotation portal, and the Apollo Annotation Editor configured to connect
      directly to our Chado database. In addition to implementing and integrating
      components of the annotation system, we have performed computational analyses to
      create gene evidence tracks and a consensus gene set, which can be viewed on
      individual gene pages at BGD. CONCLUSIONS: We have provided annotation tools that
      alleviate challenges associated with distributed annotation. Our system provides
      a consistent set of data to all annotators and eliminates the need for annotators
      to format data. Involving the bovine research community in genome annotation has
      allowed us to leverage expertise in various areas of bovine biology to provide
      biological insight into the genome sequence.

PMID- 21092106
TI  - CD4+CD25+ T regulatory cells from FIV+ cats induce a unique anergic profile in
      CD8+ lymphocyte targets.
AB  - BACKGROUND: Using the FIV model, we reported previously that CD4+CD25+ T
      regulatory (Treg) cells from FIV+ cats are constitutively activated and suppress
      CD4+CD25- and CD8+ T cell immune responses. In an effort to further explore Treg
      mediated suppression, we asked whether Treg cells induce anergy through the
      alteration of production of cyclins, cyclin-dependent kinases and their
      inhibitors. RESULTS: Lymphocytes were obtained from control or FIV+ cats and
      sorted by FACS into CD4+CD25+ and CD8+ populations. Following co-culture with
      CD4+CD25+ cells, CD8+ targets were examined by Western blot for changes in
      cyclins D3, E and A, retinoblastoma (Rb) protein, as well as the cyclin dependent
      kinase inhibitor p21cip1. Following co-culture with CD4+CD25+cells, we observed
      up-regulation of p21cip1 and cyclin E, with down-regulation of cyclin D3, in CD8+
      cells from FIV+ cats. As expected, CD8+ targets from control cats were quiescent
      with little up-regulation of p21cip1 and cyclin E. There was also a lack of Rb
      phosphorylation in CD8+ targets consistent with late G1 cell cycle arrest.
      Further, IL-2 mRNA was down regulated in CD8+ cells after co-culture with
      CD4+CD25+ Treg cells. Following CD4+CD25+ co-culture, CD8+ targets from FIV+ cats
      also had increased Foxp3 mRNA expression; however, these CD8+Foxp3+ cells did not
      exhibit suppressor function. CONCLUSIONS: Collectively, these data suggest that
      CD4+CD25+ Treg cells from FIV+ cats induce CD8+ anergy by disruption of normal G1
      to S cell cycle progression.

PMID- 21092107
TI  - The pathogenesis of low pathogenicity H7 avian influenza viruses in chickens,
      ducks and turkeys.
AB  - BACKGROUND: Avian influenza (AI) viruses infect numerous avian species, and low
      pathogenicity (LP) AI viruses of the H7 subtype are typically reported to produce
      mild or subclinical infections in both wild aquatic birds and domestic poultry.
      However relatively little work has been done to compare LPAI viruses from
      different avian species for their ability to cause disease in domestic poultry
      under the same conditions. In this study twelve H7 LPAI virus isolates from North
      America were each evaluated for their comparative pathogenesis in chickens,
      ducks, and turkeys. RESULTS: All 12 isolates were able to infect all three
      species at a dose of 106 50% egg infectious doses based on seroconversion,
      although not all animals seroconverted with each isolate-species combination. The
      severity of disease varied among isolate and species combinations, but there was
      a consistent trend for clinical disease to be most severe in turkeys where all 12
      isolates induced disease, and mortality was observed in turkeys exposed to 9 of
      the 12 viruses. Turkeys also shed virus by the oral and cloacal routes at
      significantly higher titers than either ducks or chickens at numerous time
      points. Only 3 isolates induced observable clinical disease in ducks and only 6
      isolates induced disease in chickens, which was generally very mild and did not
      result in mortality. Full genome sequence was completed for all 12 isolates and
      some isolates did have features consistent with adaptation to poultry (e.g. NA
      stalk deletions), however none of these features correlated with disease
      severity. CONCLUSIONS: The data suggests that turkeys may be more susceptible to
      clinical disease from the H7 LPAI viruses included in this study than either
      chickens or ducks. However the severity of disease and degree of virus shed was
      not clearly correlated with any isolate or group of isolates, but relied on
      specific species and isolate combinations.

PMID- 21092109
TI  - Radiological and pathological findings of a metastatic composite paraganglioma
      with neuroblastoma in a man: a case report.
AB  - INTRODUCTION: Composite tumors of the adrenal medulla or paraganglia are
      extremely rare and present a diagnostic dilemma. These tumors consist of a
      neuroendocrine component mixed with a neural component.We describe the imaging
      characteristics together with the corresponding pathological findings of a
      composite tumor. Apart from any component-specific imaging findings, the hallmark
      of this entity is the presence of histologically distinguishable components. CASE
      PRESENTATION: A 61-year-old Caucasian man was referred to our hospital due to a
      suspect lesion found on chest computed tomography carried out for unclear
      thoracic pain. An abdominal computed tomography scan and ultrasound examination
      detected a retroperitoneal tumor comprising two different tumor components.
      Twenty-four-hour urine revealed high levels of normetanephrine, characteristic of
      a neuroendocrine tumor. An octreoscan prior to surgical procedures revealed
      multiple osseous and intra-hepatic metastases. The final histopathological workup
      revealed a composite paraganglioma with neuroblastoma. Our patient died ten
      months after the initial diagnosis from tumor-associated complications.
      CONCLUSIONS: Composite paragangliomas with neuroblastoma are rare tumors of the
      retroperitoneum. Such tumors should be considered in the differential diagnosis
      of retroperitoneal masses.

PMID- 21092108
TI  - Lack of recovery in monocyte human leukocyte antigen-DR expression is
      independently associated with the development of sepsis after major trauma.
AB  - INTRODUCTION: Major trauma is characterized by an overwhelming pro-inflammatory
      response and an accompanying anti-inflammatory response that lead to a state of
      immunosuppression, as observed after septic shock. Diminished monocyte Human
      Leukocyte Antigen DR (mHLA-DR) is a reliable marker of monocyte dysfunction and
      immunosuppression. The main objective of this study was to determine the relation
      between mHLA-DR expression in severe trauma patients and the development of
      sepsis. METHODS: We conducted a prospective observational study over 23 months in
      a trauma intensive care unit at a university hospital. Patients with an Injury
      Severity Score (ISS) over 25 and age over 18 were included. mHLA-DR was assessed
      by flow cytometry protocol according to standardized protocol. Mann-Whitney U
      test for continuous non-parametric variables, independent paired t test for
      continuous parametric variables and chi-square test for categorical data were
      used. RESULTS: mHLA-DR was measured three times a week during the first 14 days.
      One hundred five consecutive severely injured patients were monitored (ISS 38 +/-
      17, SAPS II 37 +/- 16). Thirty-seven patients (35%) developed sepsis over the 14
      days post-trauma. At days 1-2, mHLA-DR was diminished in the whole patient
      population, with no difference with the development of sepsis. At days 3-4, a
      highly significant difference appeared between septic and non-septic patients.
      Non- septic patients showed an increase in mHLA-DR levels, whereas septic
      patients did not (13,723 +/- 7,766 versus 9,271 +/- 6,029 antibodies per cell, p
      = .004). Most importantly, multivariate logistic regression analysis, after
      adjustment for usual clinical confounders (adjusted OR 5.41, 95% CI 1.42-20.52),
      revealed that a slope of mHLA-DR expression between days1-2 and days 3-4 below
      1.2 remained associated with the development of sepsis. CONCLUSIONS: Major trauma
      induced an immunosuppression, characterized by a decrease in mHLA-DR expression.
      Importantly, after multivariate regression logistic analysis, persistent
      decreased expression was assessed to be in relation with the development of
      sepsis. This is the first study in trauma patients showing a link between the
      lack of immune recovery and the development of sepsis on the basis of the
      standardized protocol. Monitoring immune function by mHLA-DR measurement could be
      useful to identify trauma patients at a high risk of infection.

PMID- 21092110
TI  - Deducing corticotropin-releasing hormone receptor type 1 signaling networks from
      gene expression data by usage of genetic algorithms and graphical Gaussian
      models.
AB  - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a
      hallmark of complex and multifactorial psychiatric diseases such as anxiety and
      mood disorders. About 50-60% of patients with major depression show HPA axis
      dysfunction, i.e. hyperactivity and impaired negative feedback regulation. The
      neuropeptide corticotropin-releasing hormone (CRH) and its receptor type 1
      (CRHR1) are key regulators of this neuroendocrine stress axis. Therefore, we
      analyzed CRH/CRHR1-dependent gene expression data obtained from the pituitary
      corticotrope cell line AtT-20, a well-established in vitro model for CRHR1
      mediated signal transduction. To extract significantly regulated genes from a
      genome-wide microarray data set and to deduce underlying CRHR1-dependent
      signaling networks, we combined supervised and unsupervised algorithms. RESULTS:
      We present an efficient variable selection strategy by consecutively applying
      univariate as well as multivariate methods followed by graphical models. First,
      feature preselection was used to exclude genes not differentially regulated over
      time from the dataset. For multivariate variable selection a maximum likelihood
      (MLHD) discriminant function within GALGO, an R package based on a genetic
      algorithm (GA), was chosen. The topmost genes representing major nodes in the
      expression network were ranked to find highly separating candidate genes. By
      using groups of five genes (chromosome size) in the discriminant function and
      repeating the genetic algorithm separately four times we found eleven genes
      occurring at least in three of the top ranked result lists of the four
      repetitions. In addition, we compared the results of GA/MLHD with the alternative
      optimization algorithms greedy selection and simulated annealing as well as with
      the state-of-the-art method random forest. In every case we obtained a clear
      overlap of the selected genes independently confirming the results of MLHD in
      combination with a genetic algorithm. With two unsupervised algorithms, principal
      component analysis and graphical Gaussian models, putative interactions of the
      candidate genes were determined and reconstructed by literature mining.
      Differential regulation of six candidate genes was validated by qRT-PCR.
      CONCLUSIONS: The combination of supervised and unsupervised algorithms in this
      study allowed extracting a small subset of meaningful candidate genes from the
      genome-wide expression data set. Thereby, variable selection using different
      optimization algorithms based on linear classifiers as well as the nonlinear
      random forest method resulted in congruent candidate genes. The calculated
      interacting network connecting these new target genes was bioinformatically
      mapped to known CRHR1-dependent signaling pathways. Additionally, the
      differential expression of the identified target genes was confirmed
      experimentally.

PMID- 21092111
TI  - Sex, drugs and gender roles: mapping the use of sex and gender based analysis in
      pharmaceutical policy research.
AB  - BACKGROUND: Sex and gender sensitive inquiry is critical in pharmaceutical policy
      due to the sector's historical connection with women's health issues and due to
      the confluence of biological, social, political, and economic factors that shape
      the development, promotion, use, and effects of medicinal treatments. A growing
      number of research bodies internationally have issued laws, guidance or
      encouragement to support conducting sex and gender based analysis (SGBA) in all
      health related research. METHODS: In order to investigate the degree to which
      attempts to mainstream SGBA have translated into actual research practices in the
      field of pharmaceutical policy, we employed methods of literature scoping and
      mapping. A random sample of English-language pharmaceutical policy research
      articles published in 2008 and indexed in MEDLINE was analysed according to: 1)
      use of sex and gender related language, 2) application of sex and gender related
      concepts, and 3) level of SGBA employed. RESULTS: Two thirds of the articles
      (67%) in our sample made no mention of sex or gender. Similarly, 69% did not
      contain any sex or gender related content whatsoever. Of those that did contain
      some sex or gender content, the majority focused on sex. Only 2 of the 85
      pharmaceutical policy articles reviewed for this study were primarily focused on
      sex or gender issues; both of these were review articles. Eighty-one percent of
      the articles in our study contained no SGBA, functioning instead at a sex-blind
      or gender-neutral level, even though the majority of these (86%) were focused on
      topics with sex or gender aspects. CONCLUSIONS: Despite pharmaceutical policy's
      long entwinement with issues of sex and gender, and the emergence of
      international guidelines for the inclusion of SGBA in health research, the
      community of pharmaceutical policy researchers has not internalized, or
      "mainstreamed," the practice. Increased application of SGBA is, in most cases,
      not only appropriate for the topics under investigation, but well within the
      reach of today's pharmaceutical policy researchers.

PMID- 21092112
TI  - The Rhipicephalus (Boophilus) microplus Bm86 gene plays a critical role in the
      fitness of ticks fed on cattle during acute Babesia bovis infection.
AB  - BACKGROUND: Rhipicephalus (Boophilus) microplus is an economically important tick
      of cattle involved in the transmission of Babesia bovis, the etiological agent of
      bovine babesiosis. Commercial anti-tick vaccines based on the R. microplus Bm86
      glycoprotein have shown some effect in controlling tick infestation; however
      their efficacy as a stand-alone solution for tick control has been questioned.
      Understanding the role of the Bm86 gene product in tick biology is critical to
      identifying additional methods to utilize Bm86 to reduce R. microplus infestation
      and babesia transmission. Additionally, the role played by Bm86 in R. microplus
      fitness during B. bovis infection is unknown. RESULTS: Here we describe in two
      independent experiments that RNA interference-mediated silencing of Bm86
      decreased the fitness of R. microplus females fed on cattle during acute B. bovis
      infection. Notably, Bm86 silencing decreased the number and survival of engorged
      females, and decreased the weight of egg masses. However, gene silencing had no
      significant effect on the efficiency of transovarial transmission of B. bovis
      from surviving female ticks to their larval offspring. The results also show that
      Bm86 is expressed, in addition to gut cells, in larvae, nymphs, adult males and
      ovaries of partially engorged adult R. microplus females, and its expression was
      significantly down-regulated in ovaries of ticks fed on B. bovis-infected cattle.
      CONCLUSION: The R. microplus Bm86 gene plays a critical role during tick feeding
      and after repletion during blood digestion in ticks fed on cattle during acute B.
      bovis infection. Therefore, the data indirectly support the rationale for using
      Bm86-based vaccines, perhaps in combination with acaricides, to control tick
      infestation particularly in B. bovis endemic areas.

PMID- 21092113
TI  - DC-ATLAS: a systems biology resource to dissect receptor specific signal
      transduction in dendritic cells.
AB  - BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of
      pathway databases. Currently pathways are defined generically with respect to the
      organ or cell type where a reaction takes place. The cell type specificity of the
      reactions is the foundation of immunological research, and capturing this
      specificity is of paramount importance when using pathway-based analyses to
      decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and
      versatile resource for the interpretation of high-throughput data generated
      perturbing the signaling network of dendritic cells (DCs). RESULTS: Pathways are
      annotated using a novel data model, the Biological Connection Markup Language
      (BCML), a SBGN-compliant data format developed to store the large amount of
      information collected. The application of DC-ATLAS to pathway-based analysis of
      the transcriptional program of DCs stimulated with agonists of the toll-like
      receptor family allows an integrated description of the flow of information from
      the cellular sensors to the functional outcome, capturing the temporal series of
      activation events by grouping sets of reactions that occur at different time
      points in well-defined functional modules. CONCLUSIONS: The initiative
      significantly improves our understanding of DC biology and regulatory networks.
      Developing a systems biology approach for immune system holds the promise of
      translating knowledge on the immune system into more successful immunotherapy
      strategies.

PMID- 21092114
TI  - POLYAR, a new computer program for prediction of poly(A) sites in human
      sequences.
AB  - BACKGROUND: mRNA polyadenylation is an essential step of pre-mRNA processing in
      eukaryotes. Accurate prediction of the pre-mRNA 3'-end cleavage/polyadenylation
      sites is important for defining the gene boundaries and understanding gene
      expression mechanisms. RESULTS: 28761 human mapped poly(A) sites have been
      classified into three classes containing different known forms of polyadenylation
      signal (PAS) or none of them (PAS-strong, PAS-weak and PAS-less, respectively)
      and a new computer program POLYAR for the prediction of poly(A) sites of each
      class was developed. In comparison with polya_svm (till date the most accurate
      computer program for prediction of poly(A) sites) while searching for PAS-strong
      poly(A) sites in human sequences, POLYAR had a significantly higher prediction
      sensitivity (80.8% versus 65.7%) and specificity (66.4% versus 51.7%) However,
      when a similar sort of search was conducted for PAS-weak and PAS-less poly(A)
      sites, both programs had a very low prediction accuracy, which indicates that our
      knowledge about factors involved in the determination of the poly(A) sites is not
      sufficient to identify such polyadenylation regions. CONCLUSIONS: We present a
      new classification of polyadenylation sites into three classes and a novel
      computer program POLYAR for prediction of poly(A) sites/regions of each of the
      class. In tests, POLYAR shows high accuracy of prediction of the PAS-strong
      poly(A) sites, though this program's efficiency in searching for PAS-weak and PAS
      less poly(A) sites is not very high but is comparable to other available
      programs. These findings suggest that additional characteristics of such poly(A)
      sites remain to be elucidated. POLYAR program with a stand-alone version for
      downloading is available at http://cub.comsats.edu.pk/polyapredict.htm.

PMID- 21092116
TI  - Automated processing of label-free Raman microscope images of macrophage cells
      with standardized regression for high-throughput analysis.
AB  - BACKGROUND: Macrophages represent the front lines of our immune system; they
      recognize and engulf pathogens or foreign particles thus initiating the immune
      response. Imaging macrophages presents unique challenges, as most optical
      techniques require labeling or staining of the cellular compartments in order to
      resolve organelles, and such stains or labels have the potential to perturb the
      cell, particularly in cases where incomplete information exists regarding the
      precise cellular reaction under observation. Label-free imaging techniques such
      as Raman microscopy are thus valuable tools for studying the transformations that
      occur in immune cells upon activation, both on the molecular and organelle
      levels. Due to extremely low signal levels, however, Raman microscopy requires
      sophisticated image processing techniques for noise reduction and signal
      extraction. To date, efficient, automated algorithms for resolving sub-cellular
      features in noisy, multi-dimensional image sets have not been explored
      extensively. RESULTS: We show that hybrid z-score normalization and standard
      regression (Z-LSR) can highlight the spectral differences within the cell and
      provide image contrast dependent on spectral content. In contrast to typical
      Raman imaging processing methods using multivariate analysis, such as single
      value decomposition (SVD), our implementation of the Z-LSR method can operate
      nearly in real-time. In spite of its computational simplicity, Z-LSR can
      automatically remove background and bias in the signal, improve the resolution of
      spatially distributed spectral differences and enable sub-cellular features to be
      resolved in Raman microscopy images of mouse macrophage cells. Significantly, the
      Z-LSR processed images automatically exhibited subcellular architectures whereas
      SVD, in general, requires human assistance in selecting the components of
      interest. CONCLUSIONS: The computational efficiency of Z-LSR enables automated
      resolution of sub-cellular features in large Raman microscopy data sets without
      compromise in image quality or information loss in associated spectra. These
      results motivate further use of label free microscopy techniques in real-time
      imaging of live immune cells.

PMID- 21092115
TI  - Mechanical ventilation modulates Toll-like receptor-3-induced lung inflammation
      via a MyD88-dependent, TLR4-independent pathway: a controlled animal study.
AB  - BACKGROUND: Mechanical ventilation augments lung inflammation resulting from
      exposure to microbial products. The objective of this study was to test the
      hypothesis that ventilator-associated immune modulation requires MyD88-dependent
      signaling. Because MyD88 is a critical adapter protein utilized for pro
      inflammatory signaling by all Toll-like receptors (TLRs), with the exception of
      TLR3, as well as by the IL-1 and IL-18 receptors, MyD88 dependence would
      implicate generation of an endogenous soluble ligand recognized by one or more of
      these receptors during mechanical ventilation and would provide an opportunity
      for a potential future therapeutic intervention. METHODS: We compared the effect
      of mechanical ventilation on lung inflammation and permeability between poly(I:C)
      exposed mice with or without expression of MyD88. Poly(I:C) is a synthetic ligand
      for TLR3, the only MyD88-independent TLR, allowing isolation of the effect of
      MyD88 deletion on ventilator-augmentation of lung inflammation. Lung inflammation
      was assessed by cytokine concentration in lung tissue homogenate and
      polymorphonuclear cell (PMN) number in bronchoalveolar lavage fluid (BALF). Lung
      permeability was assessed by total protein, IgM, and intravenously injected FITC
      dextran concentrations in BALF. RESULTS: We found that MyD88 was required for
      mechanical ventilation augmentation of TLR3-induced lung inflammation and
      permeability. Because TLR4 is the most commonly reported receptor for endogenous
      ligands generated during tissue injury, we performed a second experiment
      comparing wildtype and TLR4-/- mice. We found that mechanical ventilation
      increased TLR3-mediated inflammation and permeability independent of TLR4.
      CONCLUSION: These data support the hypothesis that mechanical ventilation with
      moderate tidal volumes generates an endogenous ligand(s) recognized by MyD88
      dependent receptor(s) other than TLR4, and that this mechanism can contribute to
      the development of ventilator-associated lung inflammation and injury.
      Identification of these ligands and/or receptors could lead to new
      pharmacological treatments for ARDS.

PMID- 21092117
TI  - Solitary pulmonary metastasis from prostate sarcomatoid cancer.
AB  - BACKGROUND: Pulmonary metastasis from prostate cancer is considered to be a late
      event, and patients can be treated with chemotherapy or hormonal manipulation.
      However, there has been only a few reports on surgical resection for pulmonary
      metastasis from prostate cancer. CASE PRESENTATION: We present a surgical case of
      solitary pulmonary metastasis from prostate cancer. A 73-year-old man underwent
      pelvic evisceration for prostate cancer. Histopathological examination revealed a
      poorly differentiated adenocarcinoma with a sarcomatoid carcinoma component.
      During postoperative follow-up, chest computed tomography showed a nodular shadow
      in the lung, and thoracoscopic wedge resection of the lung was performed.
      Histopathological examination revealed a histological appearance similar to that
      of the prostate sarcomatoid carcinoma. This is the first reported case of
      solitary pulmonary metastasis from prostate sarcomatoid cancer. CONCLUSION:
      Isolated pulmonary metastasis from prostate sarcomatoid cancer is extremely rare,
      but surgery could be the treatment of choice.

PMID- 21092118
TI  - Process evaluation of appreciative inquiry to translate pain management evidence
      into pediatric nursing practice.
AB  - BACKGROUND: Appreciative inquiry (AI) is an innovative knowledge translation (KT)
      intervention that is compatible with the Promoting Action on Research in Health
      Services (PARiHS) framework. This study explored the innovative use of AI as a
      theoretically based KT intervention applied to a clinical issue in an inpatient
      pediatric care setting. The implementation of AI was explored in terms of its
      acceptability, fidelity, and feasibility as a KT intervention in pain management.
      METHODS: A mixed-methods case study design was used. The case was a surgical unit
      in a pediatric academic-affiliated hospital. The sample consisted of nurses in
      leadership positions and staff nurses interested in the study. Data on the AI
      intervention implementation were collected by digitally recording the AI
      sessions, maintaining logs, and conducting individual semistructured interviews.
      Data were analysed using qualitative and quantitative content analyses and
      descriptive statistics. Findings were triangulated in the discussion. RESULTS:
      Three nurse leaders and nine staff members participated in the study.
      Participants were generally satisfied with the intervention, which consisted of
      four 3-hour, interactive AI sessions delivered over two weeks to promote change
      based on positive examples of pain management in the unit and staff
      implementation of an action plan. The AI sessions were delivered with high
      fidelity and 11 of 12 participants attended all four sessions, where they
      developed an action plan to enhance evidence-based pain assessment documentation.
      Participants labeled AI a 'refreshing approach to change' because it was
      positive, democratic, and built on existing practices. Several barriers affected
      their implementation of the action plan, including a context of change overload,
      logistics, busyness, and a lack of organised follow-up. CONCLUSIONS: Results of
      this case study supported the acceptability, fidelity, and feasibility of AI as a
      KT intervention in pain management. The AI intervention requires minor
      refinements (e.g., incorporating continued follow-up meetings) to enhance its
      clinical utility and sustainability. The implementation process and effectiveness
      of the modified AI intervention require evaluation in a larger multisite study.

PMID- 21092119
TI  - The pathophysiology of prospective memory failure after diffuse axonal injury-
      lesion-symptom analysis using diffusion tensor imaging.
AB  - BACKGROUND: Prospective memory (PM) is one of the most important cognitive
      domains in everyday life. The neuronal basis of PM has been examined by a large
      number of neuroimaging and neuropsychological studies, and it has been suggested
      that several cerebral domains contribute to PM. For these activation studies, a
      constellation of experimental PM trials was developed and adopted to healthy
      subjects. In the present study, we used a widely used clinical PM assessment
      battery to determine the lesions attributable to PM failure, with the hypothesis
      that lesion-symptom analysis using diffusion tensor imaging (DTI) in subjects
      with diffuse axonal injury (DAI) can reveal the neuronal basis of PM in everyday
      life. RESULTS: Fourteen DAI patients (age: range of 18-36, median 24)
      participated in this study. PM failure was scored in the range of 0-6 using three
      sub-tests of the Rivermead Behavioural Memory Test. The PM scores of DAI patients
      were in the range of 2-6 (median 4.5, inter-quartile range 2.25). The severity of
      axonal injury following DAI was examined using fractional anisotropy (FA), one of
      the DTI parameters, at voxel level in each subject. We then obtained clusters
      correlated with PM failure by conducting voxel-based regression analysis between
      FA values and PM scores. Three clusters exhibited significant positive
      correlation with PM score, the left parahippocampal gyrus, left inferior parietal
      lobe, and left anterior cingulate. CONCLUSIONS: This is the first lesion-symptom
      study to reveal the neuronal basis of PM using DTI on subjects with DAI. Our
      findings suggest that the neuronal basis of PM is in the left parahippocampal
      gyrus, left inferior parietal lobe, and/or left anterior cingulate. These
      findings are similar to those of previous activation studies with loading
      experimental PM tasks.

PMID- 21092120
TI  - The overmethylated genes in Helicobacter pylori-infected gastric mucosa are
      demethylated in gastric cancers.
AB  - BACKGROUND: The transitional-CpG sites between weakly methylated genes and
      densely methylated retroelements are overmethylated in the gastric mucosa
      infected with Helicobacter pylori (H. pylori) and they are undermethylated in the
      gastric cancers depending on the level of loss of heterozygosity (LOH) events.
      This study delineated the transitional-CpG methylation patterns of CpG-island
      containing and -lacking genes in view of the retroelements. METHODS: The
      transitional-CpG sites of eight CpG-island-containing genes and six CpG-island
      lacking genes were semi-quantitatively examined by performing radioisotope
      labelling methylation-specific PCR under stringent conditions. The level of LOH
      in the gastric cancers was estimated using the 40 microsatellite markers on eight
      cancer-associated chromosomes. Each gene was scored as overmethylated or
      undermethylated based on an intermediate level of transitional-CpG methylation
      common in the H. pylori-negative gastric mucosa. RESULTS: The eight CpG-island
      genes examined were overmethylated depending on the proximity to the nearest
      retroelement in the H. pylori-positive gastric mucosa. The six CpG-island-lacking
      genes were similarly methylated in the H. pylori-positive and -negative gastric
      mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island
      genes distant from the retroelements remained overmethylated, whereas the
      overmethylation of short transitional-CpG segments close to the retroelements was
      not significant. Both the CpG-island-containing and -lacking genes tended to be
      decreasingly methylated in a LOH-level-dependent manner. CONCLUSIONS: The
      overmethylated genes under the influence of retroelement methylation in the H.
      pylori-infected stomach are demethylated in the gastric cancers influenced by
      LOH.

PMID- 21092121
TI  - The gene-reduction effect of chromosomal losses detected in gastric cancers.
AB  - BACKGROUND: The level of loss of heterozygosity (LOH) that reduces a gene dose
      and exerts a cell-adverse effect is known to be a parameter for the genetic
      staging of gastric cancers. This study investigated if the cell-adverse effect
      induced with the gene reduction was a rate-limiting factor for the LOH events in
      two distinct histologic types of gastric cancers, the diffuse- and intestinal
      types. METHODS: The pathologic specimens obtained from 145 gastric cancer
      patients were examined for the level of LOH using 40 microsatellite markers on
      eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).
      RESULTS: Most of the cancer-associated chromosomes were found to belong to the
      gene-poor chromosomes and to contain a few stomach-specific genes that were
      highly expressed. A baseline-level LOH involving one or no chromosome was
      frequent in diffuse-type gastric cancers. The chromosome 17 containing a
      relatively high density of genes was commonly lost in intestinal-type cancers but
      not in diffuse-type cancers. A high-level LOH involving four or more chromosomes
      tended to be frequent in the gastric cancers with intestinal and mixed
      differentiation. Disease relapse was common for gastric cancers with high-level
      LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and
      for the baseline-level LOH cases through the non-hematogenous route (67%).
      CONCLUSIONS: The cell-adverse effect of gene reduction is more tolerated in
      intestinal-type gastric cancers than in diffuse-type cancers, and the loss of
      high-dose genes is associated with hematogenous metastasis.

PMID- 21092122
TI  - Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac
      origin: a systematic review and meta-analysis.
AB  - BACKGROUND: Several studies have been published in the literature on the
      diagnostic accuracy of NT-pro-BNP for pleural effusions from heart failure in the
      last decade. The purpose of our study was to perform a systematic review and meta
      analysis on the diagnostic accuracy of pleural fluid NT-pro-BNP for pleural
      effusions of cardiac origin. METHODS: MEDLINE, EMBASE, PapersFirst, and the
      Cochrane collaboration and the Cochrane Register of controlled trials were
      searched. All searches were inclusive as of March 2010. Studies were only
      included if the absolute number of true-positive, false-negative, true-negative,
      and false-positive observations were available, and the "reference standards"
      were described clearly. Two investigators independently reviewed articles and
      extracted data. Quality was assessed with the Quality Assessment for Diagnostic
      Accuracy Studies (QUADAS). The bivariate model for diagnostic meta-analysis was
      used to obtain a pooled sensitivity and a pooled specificity. RESULTS: Ten
      studies (total number of patients 1120) were included in the meta-analysis. The
      average pleural fluid NT-pro-BNP level in effusions of cardiac origin was 6140
      pg/mL. The pooled sensitivity and specificity of all studies combined was 94%
      (95% CI: 90-97) and 94% (95% CI: 89-97) respectively. The pooled positive
      likelihood ratio was 15.2 (95% CI: 8.1-28.7) and the pooled negative likelihood
      ratio was 0.06 (95% CI: 0.03-0.11). The area under the ROC curve was 0.98 (95%
      CI: 0.96-0.99) and the diagnostic odds ratio was 246 (95% CI: 81-745).
      CONCLUSIONS: Pleural fluid NT-pro-BNP is a very useful biomarker with high
      diagnostic accuracy for distinguishing pleural effusions of cardiac origin.

PMID- 21092123
TI  - A SNP based linkage map of the turkey genome reveals multiple intrachromosomal
      rearrangements between the turkey and chicken genomes.
AB  - BACKGROUND: The turkey (Meleagris gallopavo) is an important agricultural species
      that is the second largest contributor to the world's poultry meat production.
      The genomic resources of turkey provide turkey breeders with tools needed for the
      genetic improvement of commercial breeds of turkey for economically important
      traits. A linkage map of turkey is essential not only for the mapping of
      quantitative trait loci, but also as a framework to enable the assignment of
      sequence contigs to specific chromosomes. Comparative genomics with chicken
      provides insight into mechanisms of genome evolution and helps in identifying
      rare genomic events such as genomic rearrangements and duplications/deletions.
      RESULTS: Eighteen full sib families, comprising 1008 (35 F1 and 973 F2) birds,
      were genotyped for 775 single nucleotide polymorphisms (SNPs). Of the 775 SNPs,
      570 were informative and used to construct a linkage map in turkey. The final map
      contains 531 markers in 28 linkage groups. The total genetic distance covered by
      these linkage groups is 2,324 centimorgans (cM) with the largest linkage group
      (81 loci) measuring 326 cM. Average marker interval for all markers across the 28
      linkage groups is 4.6 cM. Comparative mapping of turkey and chicken revealed two
      inter-, and 57 intrachromosomal rearrangements between these two species.
      CONCLUSION: Our turkey genetic map of 531 markers reveals a genome length of
      2,324 cM. Our linkage map provides an improvement of previously published maps
      because of the more even distribution of the markers and because the map is
      completely based on SNP markers enabling easier and faster genotyping assays than
      the microsatellitemarkers used in previous linkage maps. Turkey and chicken are
      shown to have a highly conserved genomic structure with a relatively low number
      of inter-, and intrachromosomal rearrangements.

PMID- 21092125
TI  - Mud crab susceptibility to disease from white spot syndrome virus is species
      dependent.
AB  - BACKGROUND: Based on a report for one species (Scylla serrata), it is widely
      believed that mud crabs are relatively resistant to disease caused by white spot
      syndrome virus (WSSV). We tested this hypothesis by determining the degree of
      susceptibility in two species of mud crabs, Scylla olivacea and Scylla
      paramamosain, both of which were identified by mitochondrial 16 S ribosomal gene
      analysis. We compared single-dose and serial-dose WSSV challenges on S. olivacea
      and S. paramamosain. FINDINGS: In a preliminary test using S. olivacea alone, a
      dose of 1 * 106 WSSV copies/g gave 100% mortality within 7 days. In a subsequent
      test, 17 S. olivacea and 13 S. paramamosain were divided into test and control
      groups for challenge with WSSV at 5 incremental, biweekly doses starting from 1 *
      104 and ending at 5 * 106 copies/g. For 11 S. olivacea challenged, 3 specimens
      died at doses between 1 * 105 and 5 * 105 copies/g and none died for 2 weeks
      after the subsequent dose (1 * 106 copies/g) that was lethal within 7 days in the
      preliminary test. However, after the final challenge on day 56 (5 * 106
      copies/g), the remaining 7 of 11 S. olivacea (63.64%) died within 2 weeks. There
      was no mortality in the buffer-injected control crabs. For 9 S. paramamosain
      challenged in the same way, 5 (55.56%) died after challenge doses between 1 * 104
      and 5 * 105 copies/g, and none died for 2 weeks after the challenge dose of 1 *
      106 copies/g. After the final challenge (5 * 106 copies/g) on day 56, no S.
      paramamosain died during 2 weeks after the challenge, and 2 of 9 WSSV-infected S.
      paramamosain (22.22%) remained alive together with the control crabs until the
      end of the test on day 106. Viral loads in these survivors were low when compared
      to those in the moribund crabs. CONCLUSIONS: S. olivacea and S. paramamosain show
      wide variation in response to challenge with WSSV. S. olivacea and S.
      paramamosain are susceptible to white spot disease, and S. olivacea is more
      susceptible than S. paramamosain. Based on our single-challenge and serial
      challenge results, and on previous published work showing that S. serrata is
      relatively unaffected by WSSV infection, we propose that susceptibility to white
      spot disease in the genus Scylla is species-dependent and may also be dose
      history dependent. In practical terms for shrimp farmers, it means that S.
      olivacea and S. paramamosain may pose less threat as WSSV carriers than S.
      serrata. For crab farmers, our results suggest that rearing of S. serrata would
      be a better choice than S. paramamosain or S. olivacea in terms of avoiding
      losses from seasonal outbreaks of white spot disease.

PMID- 21092124
TI  - Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI)
      stress.
AB  - BACKGROUND: Widespread use of chromium (Cr) contaminated fields due to careless
      and inappropriate management practices of effluent discharge, mostly from
      industries related to metallurgy, electroplating, production of paints and
      pigments, tanning, and wood preservation elevates its concentration in surface
      soil and eventually into rice plants and grains. In spite of many previous
      studies having been conducted on the effects of chromium stress, the precise
      molecular mechanisms related to both the effects of chromium phytotoxicity, the
      defense reactions of plants against chromium exposure as well as translocation
      and accumulation in rice remain poorly understood. RESULTS: Detailed analysis of
      genome-wide transcriptome profiling in rice root is reported here, following Cr
      plant interaction. Such studies are important for the identification of genes
      responsible for tolerance, accumulation and defense response in plants with
      respect to Cr stress. Rice root metabolome analysis was also carried out to
      relate differential transcriptome data to biological processes affected by Cr
      (VI) stress in rice. To check whether the Cr-specific motifs were indeed
      significantly over represented in the promoter regions of Cr-responsive genes,
      occurrence of these motifs in whole genome sequence was carried out. In the
      background of whole genome, the lift value for these 14 and 13 motifs was
      significantly high in the test dataset. Though no functional role has been
      assigned to any of the motifs, but all of these are present as promoter motifs in
      the Database of orthologus promoters. CONCLUSION: These findings clearly suggest
      that a complex network of regulatory pathways modulates Cr-response of rice. The
      integrated matrix of both transcriptome and metabolome data after suitable
      normalization and initial calculations provided us a visual picture of the
      correlations between components. Predominance of different motifs in the subsets
      of genes suggests the involvement of motif-specific transcription modulating
      proteins in Cr stress response of rice.

PMID- 21092126
TI  - Modulation of inhibitory activity of xylanase-alpha-amylase inhibitor protein
      (XAIP): binding studies and crystal structure determination of XAIP-II from
      Scadoxus multiflorus at 1.2 A resolution.
AB  - BACKGROUND: Plants produce a wide range of proteinaceous inhibitors to protect
      themselves against hydrolytic enzymes. Recently a novel protein XAIP belonging to
      a new sub-family (GH18C) was reported to inhibit two structurally unrelated
      enzymes xylanase GH11 and alpha-amylase GH13. It was shown to inhibit xylanase
      GH11 with greater potency than that of alpha-amylase GH13. A new form of XAIP
      (XAIP-II) that inhibits alpha-amylase GH13 with a greater potency than that of
      XAIP and xylanase GH11 with a lower potency than that of XAIP, has been
      identified in the extracts of underground bulbs of Scadoxus multiflorus. This
      kind of occurrence of isoforms of inhibitor proteins is a rare observation and
      offers new opportunities for understanding the principles of protein engineering
      by nature. RESULTS: In order to determine the structural basis of the enhanced
      potency of XAIP-II against alpha-amylase GH13 and its reduced potency against
      xylanase GH11 as compared to that of XAIP, we have purified XAIP-II to
      homogeneity and obtained its complete amino acid sequence using cloning
      procedure. It has been crystallized with 0.1 M ammonium sulphate as the
      precipitating agent and the three-dimensional structure has been determined at
      1.2 A resolution. The binding studies of XAIP-II with xylanase GH11 and alpha
      amylase GH13 have been carried out with surface plasmon resonance (SPR).
      CONCLUSION: The structure determination revealed that XAIP-II adopts the well
      known TIM barrel fold. The xylanase GH11 binding site in XAIP-II is formed mainly
      with loop alpha3-beta3 (residues, 102 - 118) which has acquired a
      stereochemically less favorable conformation for binding to xylanase GH11 because
      of the addition of an extra residue, Ala105 and due to replacements of two
      important residues, His106 and Asn109 by Thr107 and Ser110. On the other hand,
      the alpha-amylase binding site, which consists of alpha-helices alpha6 (residues,
      193 - 206), alpha7 (residues, 230 - 243) and loop beta6-alpha6 (residues, 180 -
      192) adopts a stereochemically more favorable conformation due to replacements of
      residues, Ser190, Gly191 and Glu194 by Ala191, Ser192 and Ser195 respectively in
      alpha-helix alpha6, Glu231 and His236 by Thr232 and Ser237 respectively in alpha
      helix alpha7. As a result, XAIP-II binds to xylanase GH11 less favorably while it
      interacts more strongly with alpha-amylase GH13 as compared to XAIP. These
      observations correlate well with the values of 4.2 * 10(-6) M and 3.4 * 10(-8) M
      for the dissociation constants of XAIP-II with xylanase GH11 and alpha-amylase
      GH13 respectively and those of 4.5 * 10(-7) M and 3.6 * 10(-6) M of XAIP with
      xylanase GH11 and alpha-amylase GH13 respectively.

PMID- 21092127
TI  - Functional divergence of the NIP III subgroup proteins involved altered selective
      constraints and positive selection.
AB  - BACKGROUND: Nod26-like intrinsic proteins (NIPs) that belong to the aquaporin
      superfamily are unique to plants. According to homology modeling and phylogenetic
      analysis, the NIP subfamily can be further divided into three subgroups with
      distinct biological functions (NIP I, NIP II, and NIP III). In some grasses, the
      NIP III subgroup proteins (NIP2s) were demonstrated to be permeable to solutes
      with larger diameter, such as silicic acid and arsenous acids. However, to date
      there is no data-mining or direct experimental evidences for the permeability of
      such larger solutes for dicot NIP2s, although they exhibit similar three
      dimensional structures as those in grasses. It is therefore intriguing to
      investigate the molecular mechanisms that drive the evolution of plant NIP2s.
      RESULTS: The NIP III subgroup is more ancient with a divergence time that
      predates the monocot-dicot split. The proliferation of NIP2 genes in modern grass
      species is primarily attributed to whole genome and segmental chromosomal
      duplication events. The structure of NIP2 genes is relatively conserved,
      possessing five exons and four introns. All NIP2s possess an ar/R filter
      consisting of G, S, G, and R, except for the cucumber CsNIP2;2, where a small G
      in the H2 is substituted with the bulkier C residue. Our maximum likelihood
      analysis revealed that NIP2s, especially the loop A (LA) region, have undergone
      strong selective pressure for adaptive evolution. The analysis at the amino acid
      level provided strong statistical evidences for the functional divergence between
      monocot and dicot NIP III subgroup proteins. In addition, several SDPs
      (Specificity Determining Positions) responsible for functional specificity were
      predicted. CONCLUSIONS: The present study provides the first evidences of
      functional divergence between dicot and monocot NIP2s, and suggests that positive
      selection, as well as a radical shift of evolutionary rate at some critical amino
      acid sites is the primary driver. These findings will expand our understanding to
      evolutionary mechanisms driving the functional diversification of monocot and
      dicot NIP III subgroup proteins.

PMID- 21092128
TI  - Peak and averaged bicoherence for different EEG patterns during general
      anaesthesia.
AB  - BACKGROUND: Changes in nonlinear neuronal mechanisms of EEG generation in the
      course of general anaesthesia have been extensively investigated in research
      literature. A number of EEG signal properties capable of tracking these changes
      have been reported and employed in anaesthetic depth monitors. The degree of
      phase coupling between different spectral components is a marker of nonlinear EEG
      generators and is claimed to be an important aspect of BIS. While bicoherence is
      the most direct measure of phase coupling, according to published research it is
      not directly used in the calculation of BIS, and only limited studies of its
      association with anaesthetic depth and level of consciousness have been
      published. This paper investigates bicoherence parameters across equal band and
      unequal band bifrequency regions, during different states of anaesthetic depth
      relating to routine clinical anaesthesia, as determined by visual inspection of
      EEG. METHODS: 41 subjects scheduled for day surgery under general anaesthesia
      were recruited into this study. EEG bicoherence was analysed using average and
      smoothed-peak estimates calculated over different regions on the bifrequency
      plane. Statistical analysis of associations between anaesthetic depth/state of
      consciousness and bicoherence estimates included linear regression using
      generalised linear mixed effects models (GLMs), ROC curves and prediction
      probability (Pk). RESULTS: Bicoherence estimates for the delta_theta region on
      the bifrequency plane were more sensitive to anaesthetic depth changes compared
      to other bifrequency regions. Smoothed-peak bicoherence displayed stronger
      associations than average bicoherence. Excluding burst suppression and large
      transients, the delta_theta peak bicoherence was significantly associated with
      level of anaesthetic depth (z = 25.74, p < 0.001 and R2 = 0.191). Estimates of Pk
      for this parameter were 0.889(0.867-0.911) and 0.709(0.689-0.729) respectively
      for conscious states and anaesthetic depth levels (comparable BIS estimates were
      0.928(0.905-0.950) and 0.801(0.786-0.816)). Estimates of linear regression and
      areas under ROC curves supported Pk findings. Bicoherence for eye movement
      artifacts were the most distinctive with respect to other EEG patterns (average
      |z| value 13.233). CONCLUSIONS: This study quantified associations between
      deepening anaesthesia and increase in bicoherence for different frequency
      components and bicoherence estimates. Increase in bicoherence was also
      established for eye movement artifacts. While identified associations extend
      earlier findings of bicoherence changes with increases in anaesthetic drug
      concentration, results indicate that the unequal band bifrequency region,
      delta_theta, provides better predictive capabilities than equal band bifrequency
      regions.

PMID- 21092130
TI  - Social capital in relation to depression, musculoskeletal pain, and psychosomatic
      symptoms: a cross-sectional study of a large population-based cohort of Swedish
      adolescents.
AB  - BACKGROUND: Social capital has lately received much attention in health research.
      The present study investigated whether two measures of subjective social capital
      were related to psychosomatic symptoms, musculoskeletal pain, and depression in a
      large population of Swedish adolescents. METHODS: A total of 7757 13-18 year old
      students anonymously completed the Survey of Adolescent Life in Vestmanland 2008
      which included questions on sociodemographic background, neighbourhood social
      capital, general social trust, and ill health. RESULTS: Low neighbourhood social
      capital and low general social trust were associated with higher rates of
      psychosomatic symptoms, musculoskeletal pain, and depression. Individuals with
      low general social trust had more than three times increased odds of being
      depressed, three times increased odds of having many psychosomatic symptoms, and
      double the odds of having many symptoms of musculoskeletal pain. CONCLUSIONS: The
      findings make an important contribution to the social capital - health debate by
      demonstrating relations between social capital factors and self-reported ill
      health in a young population.

PMID- 21092129
TI  - Categorical and continuous--disentangling the neural correlates of the carry
      effect in multi-digit addition.
AB  - BACKGROUND: Recently it was suggested that the carry effect observed in addition
      involves both categorical and continuous processing characteristics. METHODS: In
      the present study, we aimed at identifying the specific neural correlates
      associated with processing either categorical or continuous aspects of the carry
      effect in an fMRI study on multi-digit addition. RESULTS: In line with our
      expectations, we observed two distinct parts of the fronto-parietal network
      subserving numerical cognition to be associated with either one of these two
      characteristics. On the one hand, the categorical aspect of the carry effect was
      associated with left-hemispheric language areas and the basal ganglia probably
      reflecting increased demands on procedural and problem solving processes.
      Complementarily, the continuous aspect of the carry effect was associated with
      increased intraparietal activation indicating increasing demands on magnitude
      processing as well as place-value integration with increasing unit sum.
      CONCLUSIONS: In summary, the findings suggest representations and processes
      underlying the carry effect in multi-digit addition to be more complex and
      interactive than assumed previously.

PMID- 21092131
TI  - Size-assortative mating and sexual size dimorphism are predictable from simple
      mechanics of mate-grasping behavior.
AB  - BACKGROUND: A major challenge in evolutionary biology is to understand the
      typically complex interactions between diverse counter-balancing factors of
      Darwinian selection for size assortative mating and sexual size dimorphism. It
      appears that rarely a simple mechanism could provide a major explanation of these
      phenomena. Mechanics of behaviors can predict animal morphology, such like
      adaptations to locomotion in animals from various of taxa, but its potential to
      predict size-assortative mating and its evolutionary consequences has been less
      explored. Mate-grasping by males, using specialized adaptive morphologies of
      their forelegs, midlegs or even antennae wrapped around female body at specific
      locations, is a general mating strategy of many animals, but the contribution of
      the mechanics of this wide-spread behavior to the evolution of mating behavior
      and sexual size dimorphism has been largely ignored. RESULTS: Here, we explore
      the consequences of a simple, and previously ignored, fact that in a grasping
      posture the position of the male's grasping appendages relative to the female's
      body is often a function of body size difference between the sexes. Using an
      approach taken from robot mechanics we model coercive grasping of females by
      water strider Gerris gracilicornis males during mating initiation struggles. We
      determine that the male optimal size (relative to the female size), which gives
      the males the highest grasping force, properly predicts the experimentally
      measured highest mating success. Through field sampling and simulation modeling
      of a natural population we determine that the simple mechanical model, which
      ignores most of the other hypothetical counter-balancing selection pressures on
      body size, is sufficient to account for size-assortative mating pattern as well
      as species-specific sexual dimorphism in body size of G. gracilicornis.
      CONCLUSION: The results indicate how a simple and previously overlooked physical
      mechanism common in many taxa is sufficient to account for, or importantly
      contribute to, size-assortative mating and its consequences for the evolution of
      sexual size dimorphism.

PMID- 21092132
TI  - A non-BRICHOS surfactant protein c mutation disrupts epithelial cell function and
      intercellular signaling.
AB  - BACKGROUND: Heterozygous mutations of SFTPC, the gene encoding surfactant protein
      C (SP-C), cause sporadic and familial interstitial lung disease (ILD) in children
      and adults. The most frequent SFTPC mutation in ILD patients leads to a threonine
      for isoleucine substitution at position 73 (I73T) of the SP-C preprotein (proSP
      C), however little is known about the cellular consequences of SP-CI73T
      expression. RESULTS: To address this, we stably expressed SP-CI73T in cultured
      MLE-12 alveolar epithelial cells. This resulted in increased intracellular
      accumulation of proSP-C processing intermediates, which matched proSP-C species
      recovered in bronchial lavage fluid from patients with this mutation. Exposure of
      SP-CI73T cells to drugs currently used empirically in ILD therapy,
      cyclophosphamide, azathioprine, hydroxychloroquine or methylprednisolone,
      enhanced expression of the chaperones HSP90, HSP70, calreticulin and calnexin. SP
      CI73T mutants had decreased intracellular phosphatidylcholine level (PC) and
      increased lyso-PC level without appreciable changes of other phospholipids.
      Treatment with methylprednisolone or hydroxychloroquine partially restored these
      lipid alterations. Furthermore, SP-CI73T cells secreted into the medium soluble
      factors that modulated surface expression of CCR2 or CXCR1 receptors on CD4+
      lymphocytes and neutrophils, suggesting a direct paracrine influence of SP-CI73T
      on neighboring cells in the alveolar space. CONCLUSION: We show that I73T
      mutation leads to impaired processing of proSP-C in alveolar type II cells,
      alters their stress tolerance and surfactant lipid composition, and activates
      cells of the immune system. In addition, we show that some of the mentioned
      cellular aspects behind the disease can be modulated by application of
      pharmaceutical drugs commonly applied in the ILD therapy.

PMID- 21092134
TI  - Perioperative care of a patient with stroke.
AB  - Strokes and TIAs, with their high cumulative mortality and morbidity rates, are
      occurring with increasing frequency in western population 14. As such, it is
      vital for clinicians to provide optimal medical management in the perioperative
      period for those patients with this common neurological problem. This review aims
      to highlight the importance of the perioperative period and the stages of pre
      optimization that can be taken by the multi-disciplinary team to aid this 171819.
      The evidence suggests that there are significant physiological advantages to
      early invasive monitoring and high dependency care in these complex patients.
      These cohort of patients are at increased risk of development of respiratory,
      gastrointestinal, nutritional and electrolyte disturbances so a constant vigil
      should be exercised in early recognition and treatment.

PMID- 21092133
TI  - Assembling networks of microbial genomes using linear programming.
AB  - BACKGROUND: Microbial genomes exhibit complex sets of genetic affinities due to
      lateral genetic transfer. Assessing the relative contributions of parent-to
      offspring inheritance and gene sharing is a vital step in understanding the
      evolutionary origins and modern-day function of an organism, but recovering and
      showing these relationships is a challenging problem. RESULTS: We have developed
      a new approach that uses linear programming to find between-genome relationships,
      by treating tables of genetic affinities (here, represented by transformed BLAST
      e-values) as an optimization problem. Validation trials on simulated data
      demonstrate the effectiveness of the approach in recovering and representing
      vertical and lateral relationships among genomes. Application of the technique to
      a set comprising Aquifex aeolicus and 75 other thermophiles showed an important
      role for large genomes as 'hubs' in the gene sharing network, and suggested that
      genes are preferentially shared between organisms with similar optimal growth
      temperatures. We were also able to discover distinct and common genetic
      contributors to each sequenced representative of genus Pseudomonas. CONCLUSIONS:
      The linear programming approach we have developed can serve as an effective
      inference tool in its own right, and can be an efficient first step in a more
      intensive phylogenomic analysis.

PMID- 21092135
TI  - Human TOP1 residues implicated in species specificity of HIV-1 infection are
      required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and
      human cells increases permissiveness to HIV-1 infection.
AB  - BACKGROUND: Host determinants of HIV-1 viral tropism include factors from
      producer cells that affect the efficiency of productive infection and factors in
      target cells that block infection after viral entry. TRIM5alpha restricts HIV-1
      infection at an early post-entry step through a mechanism associated with rapid
      disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a
      role in HIV-1 viral tropism by incorporating into or otherwise modulating virions
      affecting the efficiency of a post-entry step, as the expression of human TOP1 in
      African Green Monkey (AGM) virion-producing cells increased the infectivity of
      progeny virions by five-fold. This infectivity enhancement required human TOP1
      residues 236 and 237 as their replacement with the AGM counterpart residues
      abolished the infectivity enhancement. Our previous studies showed that TOP1
      interacts with BTBD1 and BTBD2, two proteins which co-localize with the
      TRIM5alpha splice variant TRIM5delta in cytoplasmic bodies. Because BTBD1 and
      BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a
      splice variant of another, we investigated the potential involvement of BTBD1 and
      BTBD2 in HIV-1 restriction. RESULTS: We show that the interaction of BTBD1 and
      BTBD2 with TOP1 requires hu-TOP1 residues 236 and 237, the same residues required
      to enhance the infectivity of progeny virions when hu-TOP1 is expressed in AGM
      producer cells. Additionally, interference with the expression of BTBD2 in AGM
      and human 293T target cells increased their permissiveness to HIV-1 infection two
      to three-fold. CONCLUSIONS: These results do not exclude the possibility that
      BTBD2 may modestly restrict HIV-1 infection via colocation with TRIM5 variants in
      cytoplasmic bodies.

PMID- 21092136
TI  - Detection of a novel porcine parvovirus, PPV4, in Chinese swine herds.
AB  - To determine whether the novel porcine parvovirus type 4 (PPV4) recently reported
      in America is prevalent in China, a set of specific primers was designed and used
      for molecular survey of PPV4 among the clinical samples collected from various
      provinces of China between 2006 and 2010. The results showed that PPV4 is present
      in Chinese swine herds at a rate of 2.09% (12/573) among the clinical samples
      examined and 0.76% (1/132) among the samples taken from healthy animals. We also
      noted that PPV4 was not detected in samples taken prior to 2009. Analysis of the
      coding sequences showed that the Chinese and American PPV4 genome sequences are
      closely related with greater than 99% nucleotide sequence identity. Similar to a
      previous study, viral genomes in head-to-tail configuration of various lengths of
      the non-coding region were detected. Our findings confirmed that PPV4 is a unique
      recently discovered virus in pigs. Phylogenetically, PPV4 is most closely related
      to bovine parvovirus 2 (BPV2, which is not a Bocavirus and is not assigned to any
      Parvovirinae genus) and shares limited ORF1 (33.6%) and ORF2 (24.5%) amino acid
      identity. With respect to genome structure and organization, PPV4 encodes an ORF3
      in the middle of the viral genome that resembles the Bocavirus genus. However,
      the PPV4 ORF3 encoded protein shares minimal amino acid identity with the ORF3
      encoded proteins of the Bocavirus genus.

PMID- 21092137
TI  - Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT)
      in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) is currently the most
      effective medicine for the treatment of uncomplicated malaria. Artemisinin has
      previously been shown to increase the clearance of Plasmodium falciparum in
      malaria patients with haemoglobin E trait, but it did not increase parasite
      inhibition in an in vitro study using haemoglobin AS erythrocytes. The current
      study describes the efficacy of artemisinin derivatives on P. falciparum
      clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a
      haemoglobin enzyme deficiency, not yet studied in the same context, but
      nonetheless is a common in malaria endemic areas, associated with host protection
      against uncomplicated and severe malaria. The impact of G6PD deficiency on
      parasite clearance with ACT treatment was compared between G6PD-deficient
      patients and G6PD-normal group. METHODS: Blood samples from children and adults
      participants (1 to 70 years old) with uncomplicated P. falciparum malaria
      residing in Kambila, Mali were analysed. Study participants were randomly
      assigned to receive either artemether-lumefantrine (Coartem(r)) or artesunate
      plus mefloquine (ArtequinTM). A restriction-fragment length polymorphism analysis
      of PCR-amplified DNA samples was used to identify the (A-) allele of the gene
      mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus
      analysed and of these, DNA was extracted from 315 samples using the QIAamp kit
      for PCR to identify the G6PD*A- gene. RESULTS: The DNA amplified from 315 samples
      using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%).
      The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for
      homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median
      parasitaemia and other baseline characteristics (mean haemoglobin, sex and age
      groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and
      G6PD-normal participants were comparable (p > 0.05). After treatment, parasite
      clearance did not change significantly whether the participants were G6PD
      deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day
      2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). CONCLUSIONS: The presence of G6PD
      deficiency does not appear to significantly influence the clearance of P.
      falciparum in the treatment of uncomplicated malaria using ACT.

PMID- 21092138
TI  - Expression of 3-hydroxy-3-methylglutaryl-CoA reductase, p-hydroxybenzoate-m
      geranyltransferase and genes of phenylpropanoid pathway exhibits positive
      correlation with shikonins content in arnebia [Arnebia euchroma (Royle)
      Johnston].
AB  - BACKGROUND: Geranyl pyrophosphate (GPP) and p-hydroxybenzoate (PHB) are the basic
      precursors involved in shikonins biosynthesis. GPP is derived from mevalonate
      (MVA) and/or 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway(s), depending upon
      the metabolite and the plant system under consideration. PHB, however, is
      synthesized by only phenylpropanoid (PP) pathway. GPP and PHB are central
      moieties to yield shikonins through the synthesis of m-geranyl-p-hydroxybenzoate
      (GHB). Enzyme p-hydroxybenzoate-m-geranyltransferase (PGT) catalyses the coupling
      of GPP and PHB to yield GHB. The present research was carried out in shikonins
      yielding plant arnebia [Arnebia euchroma (Royle) Johnston], wherein no molecular
      work has been reported so far. The objective of the work was to identify the
      preferred GPP synthesizing pathway for shikonins biosynthesis, and to determine
      the regulatory genes involved in the biosynthesis of GPP, PHB and GHB. RESULTS: A
      cell suspension culture-based, low and high shikonins production systems were
      developed to facilitate pathway identification and finding the regulatory gene.
      Studies with mevinolin and fosmidomycin, inhibitors of MVA and MEP pathway,
      respectively suggested MVA as a preferred route of GPP supply for shikonins
      biosynthesis in arnebia. Accordingly, genes of MVA pathway (eight genes), PP
      pathway (three genes), and GHB biosynthesis were cloned. Expression studies
      showed down-regulation of all the genes in response to mevinolin treatment,
      whereas gene expression was not influenced by fosmidomycin. Expression of all the
      twelve genes vis-a-vis shikonins content in low and high shikonins production
      system, over a period of twelve days at frequent intervals, identified critical
      genes of shikonins biosynthesis in arnebia. CONCLUSION: A positive correlation
      between shikonins content and expression of 3-hydroxy-3-methylglutaryl-CoA
      reductase (AeHMGR) and AePGT suggested critical role played by these genes in
      shikonins biosynthesis. Higher expression of genes of PP pathway was a general
      feature for higher shikonins biosynthesis.

PMID- 21092139
TI  - Malignant inguinal monophasic synovial sarcoma: report of a case and review of
      the literature.
AB  - BACKGROUND: A synovial sarcoma (SS) is an aggressive soft tissue tumor that
      classically occurs in the extremities near, but rarely within large joints, in
      young adults. Variable symptoms and clinical manifestations may be encountered
      and a definite diagnosis should depend on pathological results. This poses
      certain difficulties in arriving at a prompt diagnosis and appropriate treatment.
      CASE PRESENTATION: We report the case of a 68-year-old woman patient who
      presented an inguinal mass with swelling and pain in the right lower limb. She
      underwent surgery, and later received systematic intravenous chemotherapy. The
      pathological studies, especially the specific chromosomal translocation of a
      t(X;18) (p11.2;q11.2), confirmed the diagnosis as a synovial sarcoma. To the best
      of our knowledge, this is the first report of a monophasic synovial sarcoma in
      the inguinal region. CONCLUSION: Besides making the readership aware of the
      rarity of location and age of this present case, this report distinctly
      highlights the great value of a molecular analysis of an SYT associated genetic
      alteration in the diagnosis of synovial sarcoma occurring at rare sites
      especially when immunochemical results are equivocal.

PMID- 21092140
TI  - Quality assessment in surgery: mission impossible?

PMID- 21092141
TI  - GSK3 regulates the expressions of human and mouse c-Myb via different mechanisms.
AB  - BACKGROUND: c-Myb is expressed at high levels in immature progenitors of all the
      hematopoietic lineages. It is associated with the regulation of proliferation,
      differentiation and survival of erythroid, myeloid and lymphoid cells, but
      decreases during the terminal differentiation to mature blood cells. The cellular
      level of c-Myb is controlled by not only transcriptional regulation but also
      ubiquitin-dependent proteolysis. We recently reported that mouse c-Myb protein is
      controlled by ubiquitin-dependent degradation by SCF-Fbw7 E3 ligase via glycogen
      synthase kinase 3 (GSK3)-mediated phosphorylation of Thr-572 in a Cdc4
      phosphodegron (CPD)-dependent manner. However, this critical threonine residue is
      not conserved in human c-Myb. In this study, we investigated whether GSK3 is
      involved in the regulatory mechanism for human c-Myb expression. RESULTS: Human c
      Myb was degraded by ubiquitin-dependent degradation via SCF-Fbw7. Human Fbw7
      ubiquitylated not only human c-Myb but also mouse c-Myb, whereas mouse Fbw7
      ubiquitylated mouse c-Myb but not human c-Myb. Human Fbw7 mutants with mutations
      of arginine residues important for recognition of the CPD still ubiquitylated
      human c-Myb. These data strongly suggest that human Fbw7 ubiquitylates human c
      Myb in a CPD-independent manner. Mutations of the putative GSK3 phosphorylation
      sites in human c-Myb did not affect the Fbw7-dependent ubiquitylation of human c
      Myb. Neither chemical inhibitors nor a siRNA for GSK3beta affected the stability
      of human c-Myb. However, depletion of GSK3beta upregulated the transcription of
      human c-Myb, resulting in transcriptional suppression of gamma-globin, one of the
      c-Myb target genes. CONCLUSIONS: The present observations suggest that human Fbw7
      ubiquitylates human c-Myb in a CPD-independent manner, whereas mouse Fbw7
      ubiquitylates human c-Myb in a CPD-dependent manner. Moreover, GSK3 negatively
      regulates the transcriptional expression of human c-Myb but does not promote Fbw7
      dependent degradation of human c-Myb protein. Inactivation of GSK3 as well as
      mutations of Fbw7 may be causes of the enhanced c-Myb expression observed in
      leukemia cells. We conclude that expression levels of human and mouse c-Myb are
      regulated via different mechanisms.

PMID- 21092142
TI  - Subcellular distribution of nuclear import-defective isoforms of the
      promyelocytic leukemia protein.
AB  - BACKGROUND: The promyelocytic leukemia (PML) protein participates in a number of
      cellular processes, including transcription regulation, apoptosis,
      differentiation, virus defense and genome maintenance. This protein is
      structurally organized into a tripartite motif (TRIM) at its N-terminus, a
      nuclear localization signal (NLS) at its central region and a C-terminus that
      varies between alternatively spliced isoforms. Most PML splice variants target
      the nucleus where they define sub-nuclear compartments termed PML nuclear bodies
      (PML NBs). However, PML variants that lack the NLS are also expressed, suggesting
      the existence of PML isoforms with cytoplasmic functions. In the present study we
      expressed PML isoforms with a mutated NLS in U2OS cells to identify potential
      cytoplasmic compartments targeted by this protein. RESULTS: Expression of NLS
      mutated PML isoforms in U2OS cells revealed that PML I targets early endosomes,
      PML II targets the inner nuclear membrane (partially due to an extra NLS at its C
      terminus), and PML III, IV and V target late endosomes/lysosomes. Clustering of
      PML at all of these subcellular locations depended on a functional TRIM domain.
      CONCLUSIONS: This study demonstrates the capacity of PML to form macromolecular
      protein assemblies at several different subcellular sites. Further, it emphasizes
      a role of the variable C-terminus in subcellular target selection and a general
      role of the N-terminal TRIM domain in promoting protein clustering.

PMID- 21092143
TI  - Prevalence of active hepatitis c virus infection in district Mansehra Pakistan.
AB  - Prevalence of active hepatitis C virus (HCV) infection in apparently healthy
      inhabitants of District Mansehra, Pakistan was surveyed during September, 2009 to
      May, 2010. Subjects of different age and gender groups were analyzed through
      random blood sampling from people of three areas viz; Tehsil Mansehra, Tehsil
      Balakot and Tehsil Oghi. Sum of 400 individuals, 300 male and 100 females with
      age groups from 10 years to 50 and above were included in the study. All the
      individuals were screened for antibodies against HCV. The positive samples thus
      screened, were subjected to polymerase chain reaction (PCR) analysis for
      detection of HCV-RNA. The results showed that 3.5% of the people of District
      Mansehra are actively infected with HCV whereas 7% of the population in general,
      has the presence of antibodies against HCV in their blood. It was also concluded
      that the prevalence of active HCV infection was high 4% in males as compared to
      females (2%). The prevalence of HCV proportionality increases with the increase
      in age of the people. Its incidence was highest (7.69%) in the people of the age
      group of 51 years and above, whereas no sign of infection was recorded for the
      age group of 10-20 years.

PMID- 21092145
TI  - Systems medicine and the integration of bioinformatic tools for the diagnosis of
      Alzheimer's disease.
AB  - Because of the changes in demographic structure, the prevalence of Alzheimer's
      disease is expected to rise dramatically over the next decades. The progression
      of this degenerative and terminal disease is gradual, with the subclinical stage
      of illness believed to span several decades. Despite this, no therapy to prevent
      or cure Alzheimer's disease is currently available. Early disease detection is
      still important for delaying the onset of the disease with pharmacological
      treatment and/or lifestyle changes, assessing the efficacy of potential
      therapeutic agents, or monitoring disease progression more closely using medical
      imaging. Sensitive cerebrospinal-fluid-derived marker candidates exist, but given
      the invasiveness of sample collection their use in routine diagnostics may be
      limited. The pathogenesis of Alzheimer's disease is complex and poorly
      understood. There is thus a strong case for integrating information across
      multiple physiological levels, from molecular profiling (metabolomics,
      lipidomics, proteomics and transcriptomics) and brain imaging to cognitive
      assessments. To facilitate the integration of heterogeneous data, such as
      molecular and image data, sophisticated statistical approaches are needed to
      segment the image data and study their dependencies on molecular changes in the
      same individuals. Molecular profiling, combined with biophysical modeling of
      molecular assemblies associated with the disease, offer an opportunity to link
      the molecular pathway changes with cell- and tissue-level physiology and
      structure. Given that data acquired at different levels can carry complementary
      information about early Alzheimer's disease pathology, it is expected that their
      integration will improve early detection as well as our understanding of the
      disease.

PMID- 21092146
TI  - Genetic discovery: the prescription for chronic pain.
AB  - A recent publication that combined rat gene expression data and a human genetic
      association study has identified the first genetic risk factor for chronic pain
      in humans. In four of the five cohorts studied, there was a significant
      association of an allele within a gene (KCNS1) encoding a potassium channel
      (Kv9.1) with an increased risk for chronic pain. Identification of genetic risk
      factors for chronic pain could catalyze new advances in this difficult clinical
      area that has become a major public health problem. Genomic-medicine-based
      advances for chronic pain could include the development of a mechanism-based
      classification system for chronic pain, new treatment options, improved methods
      for treatment selection and targeted prevention strategies for high-risk
      individuals.

PMID- 21092147
TI  - Preventing severe hypoxia during emergent intubation: is nasopharyngeal
      oxygenation the answer?
AB  - Critically ill patients requiring emergent endotracheal intubation are at risk
      for life-threatening hypoxemia during the intubation procedure, particularly when
      the patient is apneic and not receiving any supplemental oxygen. In a current
      study, Engstrom and colleagues investigated the effect of nasopharyngeal
      oxygenation in eight anesthetized pigs with induced acute lung injury. The
      investigators confirmed, even in this model, that pharyngeal oxygenation
      significantly prolonged the time to desaturation during periods of apnea.
      Recognizing the limitations of directly extrapolating these experimental results
      to critically ill human subjects, the findings do support the contention that,
      until proven otherwise, nasopharyngeal oxygenation should at least be considered
      as one technique to diminish hypoxemic complications in very sick patients,
      particularly those with underlying pulmonary impairment.

PMID- 21092148
TI  - Predicting prognosis of breast cancer with gene signatures: are we lost in a sea
      of data?
AB  - A large number of prognostic and predictive signatures have been proposed for
      breast cancer and a few of these are now available in the clinic as new molecular
      diagnostic tests. However, several other signatures have not fared well in
      validation studies. Some investigators continue to be puzzled by the diversity of
      signatures that are being developed for the same purpose but that share few or no
      common genes. The history of empirical development of prognostic gene signatures
      and the unique association between molecular subsets and clinical phenotypes of
      breast cancer explain many of these apparent contradictions in the literature.
      Three features of breast cancer gene expression contribute to this: the large
      number of individually prognostic genes (differentially expressed between good
      and bad prognosis cases); the unstable rankings of differentially expressed genes
      between datasets; and the highly correlated expression of informative genes.

PMID- 21092149
TI  - New concepts on the immune modulation mediated by mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are the nonhematopoietic multipotent progenitor
      cells found in various adult tissues. They are characterized by their ease of
      isolation and their rapid growth in vitro while maintaining their differentiation
      potential, allowing for extensive expansion in culture that yields large
      quantities suitable for therapeutic use. This article reviews the
      immunomodulatory activities associated with MSCs. Numerous studies have
      demonstrated that MSCs are potently immunosuppressive in vitro and in vivo.
      However, this article presents a new paradigm in MSC biology, in which MSCs, at
      least in vitro, can undergo polarization into either a pro-inflammatory or an
      immunosuppressive phenotype.

PMID- 21092150
TI  - The autoimmune tautology.
AB  - Although autoimmune diseases exhibit contrasting epidemiological features,
      pathology, and clinical manifestations, three lines of evidence demonstrate that
      these diseases share similar immunogenetic mechanisms (that is, autoimmune
      tautology). First, clinical evidence highlights the co-occurrence of distinct
      autoimmune diseases within an individual (that is, polyautoimmunity) and within
      members of a nuclear family (that is, familial autoimmunity). Second,
      physiopathologic evidence indicates that the pathologic mechanisms may be similar
      among autoimmune diseases. Lastly, genetic evidence shows that autoimmune
      phenotypes might represent pleiotropic outcomes of the interaction of non
      specific disease genes.

PMID- 21092151
TI  - Rational or rationalized choices in fluid resuscitation?
AB  - The war between colloids and crystalloids wages on. In a large multinational
      survey of fluid prescribing practices in critically ill patients, we have a new
      and intriguing snapshot of global fluid resuscitation practices. Colloids are
      more often used for impaired perfusion or low cardiac output, and the choice of
      colloid or crystalloid varies enormously between countries. Why are some ICUs
      prescribing colloids more often than crystalloids when there is little convincing
      evidence that colloids are superior for fluid resuscitation? Are colloids
      advantageous in certain diseases, or in specific regional patient populations
      that have not yet been elucidated? Perhaps we should look inwards: the answer may
      not be more randomized clinical trials, but better adherence to current
      guidelines and treatment recommendations.

PMID- 21092152
TI  - The esophagus ... not just for food anymore?

PMID- 21092153
TI  - Are primary care practitioners in Barbados following hypertension guidelines? - a
      chart audit.
AB  - BACKGROUND: About 55% of the population 40 to 80 years of age in Barbados is
      hypertensive. The quality of hypertension primary care compared to available
      practice guidelines is uncertain. FINDINGS: Charts of hypertensive and diabetic
      patients were randomly sampled at all public and 20 private sector primary care
      clinics. Charts of all hypertensive patients >= 40 years of age were then
      selected and processes of care and blood pressure (BP) maintenance < 140/90
      documented.343 charts of hypertensive patients (170 public, and 173 private) were
      audited. Patients had the following characteristics: mean age 64 years, female
      gender 63%, mean duration of diagnosis 9.1 years, and diabetes diagnosed 58%.
      Patients had an average of 4.7 clinic visits per year, 70% were prescribed a
      thiazide diuretic, 42% a calcium channel blocker, 40% an angiotensin receptor
      blocker, and 19% a beta blocker. Public patients compared to private patients
      were more likely to be female (73% vs. 52%, p < 0.01); have a longer duration of
      diagnosis (11.7 vs. 6.5 years, p < 0.01), and more clinic visits per year (5.0
      vs. 4.5, p < 0.01). Over a 2 year period, the proportion of charts with the
      following recorded at least once was: BP 98%, weight 80%, total cholesterol 71%,
      urine tested for albumin 67%, serum creatinine 59%, dietary advice 55%, lipid
      profile 48%, exercise advice 45%, fasting blood glucose for non-diabetics 39%,
      dietician referral 21%, tobacco advice 17%, retinal examination 16%, body mass
      index 1%, and waist circumference 0%. Public patients were more likely to have
      recorded: weight (92% vs. 68%, p = < 0.01); tests for total cholesterol (77% vs.
      67%, p = 0.04), albuminuria (77% vs. 58%, p = < 0.01), serum creatinine (75% vs.
      43%, p < 0.01), and fasting blood glucose for non-diabetics (49% vs. 30%, p =
      0.02); dietician referral (34% vs. 9%, p < 0.01), and tobacco advice (24% vs.
      10%, p < 0.01). Most (92%) diastolic BP readings ended in 0 or 5 (72% ended in
      0). At the last visit 36% of patients had a BP < 140/90 mmHg. CONCLUSIONS:
      Improvements are needed in following guidelines for basic interventions such as
      body mass assessment, accurate BP measurement, use of thiazide diuretics and
      lifestyle advice. BP control is inadequate.

PMID- 21092154
TI  - Adiponectin levels in people with Latent Autoimmune Diabetes-a case control
      study.
AB  - BACKGROUND: To examine adiponectin levels in people with Latent Autoimmune
      Diabetes in Adults using a matched pair case control study. FINDINGS: Patients
      with LADA (n = 64), were matched for sex with type 2 diabetic and non-diabetic
      controls. A matched paired T-test was used to examine average adiponectin levels
      in the LADA patients' versus controls. The average adiponectin level for the LADA
      patients was 9.96 MUg/ml compared to 6.4 MUg/ml for Type 2 matched controls and
      9.6 MUg/ml for non-diabetic controls. Mean difference for the LADA-type 2
      comparison was calculated after data was log transformed and showed a difference
      of 1.58 MUg/ml (95%CI: 1.28-1.95, p = 0.0001). There was no significant
      difference between LADA and non-diabetic controls (p = 0.54). CONCLUSIONS:
      Adiponectin levels are higher among people with LADA compared to those with type
      2 diabetes and are equivalent to levels seen in non-diabetic controls. This
      suggests that risk of complications in LADA, as with type 1 diabetes may be
      related more to glycaemic control rather than to factors of the metabolic
      syndrome.

PMID- 21092155
TI  - Identification of Pns6, a putative movement protein of RRSV, as a silencing
      suppressor.
AB  - RNA silencing is a potent antiviral response in plants. As a counterdefense, most
      plant and some animal viruses encode RNA silencing suppressors. In this study, we
      showed that Pns6, a putative movement protein of Rice ragged stunt virus (RRSV),
      exhibited silencing suppressor activity in coinfiltration assays with the
      reporter green fluorescent protein (GFP) in transgenic Nicotiana benthamiana line
      16c. Pns6 of RRSV suppressed local silencing induced by sense RNA but had no
      effect on that induced by dsRNA. Deletion of a region involved in RNA binding
      abolished the silencing suppressor activity of Pns6. Further, expression of Pns6
      enhanced Potato virus * pathogenicity in N. benthamiana. Collectively, these
      results suggested that RRSV Pns6 functions as a virus suppressor of RNA silencing
      that targets an upstream step of the dsRNA formation in the RNA silencing
      pathway. This is the first silencing suppressor to be identified from the genus
      Oryzavirus.

PMID- 21092156
TI  - IP-10 detection in urine is associated with lung diseases.
AB  - BACKGROUND: Blood cytokines and chemokines have been proposed as biomarkers for
      tuberculosis (TB). Recently, some immune mediators found in the urine of patients
      with renal dysfunctions have also been suggested as potential biomarkers. Finding
      biomarkers for TB in urine would present several advantages over blood in terms
      of collection and safety. The objective of this study was to investigate the
      presence of cytokines and chemokines in the urine of patients with pulmonary TB
      at the time of diagnosis. In a subgroup, the evaluation was also performed during
      TB treatment and at therapy completion. Patients with lung diseases other than
      TB, and healthy subjects were also enrolled. METHODS: Urine samples from 138
      individuals, after exclusion of renal dysfunctions, were collected during an 18
      month-period. Among them, 58 received a diagnosis of pulmonary TB, 28 resulted
      having lung diseases other than TB, and 34 were healthy subjects. Moreover, 18 TB
      patients, 9 of whom were tested 2 months after AFB smear sputum reversion and 9
      of whom were cured of TB were also included. Cytokines and chemokines in urine
      were evaluated using a Cytometric-Bead-Array-Flex-Set. IP-10 detection in 49
      subjects was also carried out in parallel by using an Enzyme Linked ImmunoSorbent
      Assay (ELISA). RESULTS: IFN-gamma, TNF-alpha, IL-2, IL-8, MIP-1alpha, MIP-1beta
      and RANTES were poorly detected in all urine samples. Conversely, IP-10 was
      consistently detected in urine and its level was significantly increased in
      patients with lung disease compared to healthy subjects (p < 0.001). Increased IP
      10 levels were found in both pulmonary TB and lung diseases other than TB.
      Moreover lower IP-10 levels were found in cured-TB patients compared to the
      levels at the time of diagnosis, and this difference was close to significance (p
      = 0.06). Interestingly, we demonstrated a significant correlation between the
      data obtained by flow cytometry and ELISA (r2 0.82, p < 0.0001). CONCLUSIONS: IP
      10, in contrast to IFN-gamma, TNF-alpha, IL-2, IL-8, MIP-1alpha, MIP-1beta and
      RANTES, is detectable in the urine of patients with pulmonary diseases in the
      absence of renal dysfunctions. Moreover, the IP-10 level in cured-TB patients is
      comparable to that found in healthy subjects. More studies are needed to further
      investigate the clinical utility of these findings.

PMID- 21092158
TI  - Biodetoxification of toxins generated from lignocellulose pretreatment using a
      newly isolated fungus, Amorphotheca resinae ZN1, and the consequent ethanol
      fermentation.
AB  - BACKGROUND: Degradation of the toxic compounds generated in the harsh
      pretreatment of lignocellulose is an inevitable step in reducing the toxin level
      for conducting practical enzymatic hydrolysis and ethanol fermentation processes.
      Various detoxification methods have been tried and many negative outcomes were
      found using these methods, such as the massive freshwater usage and wastewater
      generation, loss of the fine lignocellulose particles and fermentative sugars and
      incomplete removal of inhibitors. An alternate method, biodetoxification, which
      degrades the toxins as part of their normal metabolism, was considered a
      promising option for the removal of toxins without causing the above problems.
      RESULTS: A kerosene fungus strain, Amorphotheca resinae ZN1, was isolated from
      the microbial community growing on the pretreated corn stover material. The
      degradation of the toxins as well as the lignocelluloses-derived sugars was
      characterized in different ways, and the results show that A. resinae ZN1
      utilized each of these toxins and sugars as the sole carbon sources efficiently
      and grew quickly on the toxins. It was found that the solid-state culture of A.
      resinae ZN1 on various pretreated lignocellulose feedstocks such as corn stover,
      wheat straw, rice straw, cotton stalk and rape straw degraded all kinds of toxins
      quickly and efficiently. The consequent simultaneous saccharification and ethanol
      fermentation was performed at the 30% (wt/wt) solid loading of the detoxified
      lignocellulosic feedstocks without a sterilization step, and the ethanol titer in
      the fermentation broth reached above 40 g/L using food crop residues as
      feedstocks. CONCLUSIONS: The advantages of the present biodetoxification by A.
      resinae ZN1 over the known detoxification methods include zero energy input, zero
      wastewater generation, complete toxin degradation, processing on solid pretreated
      material, no need for sterilization and a wide lignocellulose feedstock spectrum.
      These advantages make it possible for industrial applications with fast and
      efficient biodetoxification to remove toxins generated during intensive
      lignocellulose pretreatment.

PMID- 21092157
TI  - Peptide binding predictions for HLA DR, DP and DQ molecules.
AB  - BACKGROUND: MHC class II binding predictions are widely used to identify epitope
      candidates in infectious agents, allergens, cancer and autoantigens. The vast
      majority of prediction algorithms for human MHC class II to date have targeted
      HLA molecules encoded in the DR locus. This reflects a significant gap in
      knowledge as HLA DP and DQ molecules are presumably equally important, and have
      only been studied less because they are more difficult to handle experimentally.
      RESULTS: In this study, we aimed to narrow this gap by providing a large scale
      dataset of over 17,000 HLA-peptide binding affinities for a set of 11 HLA DP and
      DQ alleles. We also expanded our dataset for HLA DR alleles resulting in a total
      of 40,000 MHC class II binding affinities covering 26 allelic variants. Utilizing
      this dataset, we generated prediction tools utilizing several machine learning
      algorithms and evaluated their performance. CONCLUSION: We found that 1)
      prediction methodologies developed for HLA DR molecules perform equally well for
      DP or DQ molecules. 2) Prediction performances were significantly increased
      compared to previous reports due to the larger amounts of training data
      available. 3) The presence of homologous peptides between training and testing
      datasets should be avoided to give real-world estimates of prediction performance
      metrics, but the relative ranking of different predictors is largely unaffected
      by the presence of homologous peptides, and predictors intended for end-user
      applications should include all training data for maximum performance. 4) The
      recently developed NN-align prediction method significantly outperformed all
      other algorithms, including a naive consensus based on all prediction methods. A
      new consensus method dropping the comparably weak ARB prediction method could
      outperform the NN-align method, but further research into how to best combine MHC
      class II binding predictions is required.

PMID- 21092159
TI  - Adult asthma and traffic exposure at residential address, workplace address, and
      self-reported daily time outdoor in traffic: A two-stage case-control study.
AB  - BACKGROUND: Most epidemiologic studies use traffic at residential address as a
      surrogate for total traffic exposure when investigating effects of traffic on
      respiratory health. This study used GIS (Geographical Information Systems) to
      estimate traffic exposure, not only on residential, but also on workplace
      address, in addition to survey questions on time spent in traffic during
      commuting or other daily activities.The aim was to investigate 1) if there is an
      association between traffic exposure and prevalence of adult asthma and asthma
      symptoms, and 2) if so, does this association become stronger using more complete
      traffic exposure information. METHODS: This study was conducted in two stages: A
      first cross-sectional survey in Southern Sweden 2004 (n = 24819, 18-80 years,
      response rate 59%) was followed by a case-control study in 2005 to obtain more
      detailed exposure and confounder information (n = 2856, asthmatics and controls
      (1:3), 86% response rate). In the first survey, only residential address was
      known. In the second survey, questions about workplace addresses and daily time
      spent in traffic were also included. Residential and workplace addresses were
      geocoded and linked with GIS to road data and dispersion modelled outdoor
      concentrations of NOx (annual mean, 250 * 250 m resolution). RESULTS: Living
      within 50 m of a road (measured by GIS) with traffic intensity of >10 cars/minute
      (compared with no road within this distance) was associated with an increased
      prevalence of asthma, (OR = 1.8, 95% CI = (1.1-2.8), and with asthma symptoms
      last 12 months. No statistically significant effects were seen for traffic
      exposure at workplace address, daily time spent in traffic, or commuting time to
      work, after adjustment for confounders. A combined total exposure estimate did
      not give a stronger association with asthma prevalence or asthma symptoms.
      CONCLUSIONS: Traffic exposure at close proximity to residential address showed
      association with asthma prevalence and asthma symptoms last 12 months, among
      adults in southern Sweden. The associations were not stronger when accounting for
      total traffic exposure. This could reflect exposure misclassfication at workplace
      address and for other daily time in traffic, but also that residential address
      remains the main determinant for traffic exposure among adults.

PMID- 21092160
TI  - Improving medical students' attitudes towards the chronic sick: a role for social
      science research.
AB  - BACKGROUND: Many medical students are negatively disposed toward the elderly and
      chronic sick. The present study assessed the impact of a community-based teaching
      initiative, the Life History Project, on students' attitudes to these groups.
      METHODS: A questionnaire including Likert based responses and free text comments
      was distributed to all first-year MBChB students after completion of their Life
      History coursework. Data was analysed using SPSS and content analysis. RESULTS: A
      high proportion of students believed the Life History Project had increased their
      understanding of both psychological and social aspects of health and illness and
      the role of the humanistic social sciences within this. We discovered that the
      Life History Project not only gave students first-hand experience of the elderly
      and chronic sick but also had a positive effect on their attitudes towards these
      groups. The qualitative free text comments corroborated these views. CONCLUSIONS:
      It is possible to positively influence medical students' attitudes towards these
      stigmatised groups; it is therefore important that we continue to enhance
      opportunities for learning about the impact of chronic illness on individuals and
      society throughout the curriculum.

PMID- 21092161
TI  - Improving diaper design to address incontinence associated dermatitis.
AB  - BACKGROUND: Incontinence associated dermatitis (IAD) is an inflammatory skin
      disease mainly triggered by prolonged skin contact with urine, feces but also
      liberal detergent use when cleansing the skin. To minimize the epidermal barrier
      challenge we optimized the design of adult incontinence briefs. In the fluid
      absorption area we interposed a special type of acidic, curled-type of cellulose
      between the top sheet in contact with the skin and the absorption core beneath
      containing the polyacrylate superabsorber. The intention was to minimize
      disturbance of the already weak acid mantle of aged skin. We also employed air
      permeable side panels to minimize skin occlusion and swelling of the stratum
      corneum. METHODS: The surface pH of diapers was measured after repeated wetting
      with a urine substitute fluid at the level of the top sheet. Occlusive effects
      and hydration of the stratum corneum were measured after a 4 hour application of
      different side panel materials by corneometry on human volunteers. Finally, we
      evaluated skin symptoms in 12 patients with preexisting IAD for 21 days following
      the institutional switch to the optimized diaper design. Local skin care
      protocols remained in place unchanged. RESULTS: The improved design created a
      surface pH of 4.6 which was stable even after repeated wetting throughout a 5
      hour period. The "standard design" briefs had values of 7.1, which is alkaline
      compared to the acidic surface of normal skin. Side panels made from non-woven
      material with an air-permeability of more than 1200 l/m2/s avoided excessive
      hydration of the stratum corneum when compared to the commonly employed air
      impermeable plastic films. Resolution of pre-existing IAD skin lesions was noted
      in 8 out of 12 patients after the switch to the optimized brief design.
      CONCLUSIONS: An improved design of adult-type briefs can create an acidic pH on
      the surface and breathable side panels avoid over-hydration of the stratum
      corneum and occlusion. This may support the epidermal barrier function and may
      help to reduce the occurrence of IAD.

PMID- 21092162
TI  - Role of oxidative stress on diesel-enhanced influenza infection in mice.
AB  - Numerous studies have shown that air pollutants, including diesel exhaust (DE),
      reduce host defenses, resulting in decreased resistance to respiratory
      infections. This study sought to determine if DE exposure could affect the
      severity of an ongoing influenza infection in mice, and examine if this could be
      modulated with antioxidants. BALB/c mice were treated by oropharyngeal aspiration
      with 50 plaque forming units of influenza A/HongKong/8/68 and immediately exposed
      to air or 0.5 mg/m3 DE (4 hrs/day, 14 days). Mice were necropsied on days 1, 4, 8
      and 14 post-infection and lungs were assessed for virus titers, lung
      inflammation, immune cytokine expression and pulmonary responsiveness (PR) to
      inhaled methacholine. Exposure to DE during the course of infection caused an
      increase in viral titers at days 4 and 8 post-infection, which was associated
      with increased neutrophils and protein in the BAL, and an early increase in PR.
      Increased virus load was not caused by decreased interferon levels, since IFN
      beta levels were enhanced in these mice. Expression and production of IL-4 was
      significantly increased on day 1 and 4 p.i. while expression of the Th1
      cytokines, IFN-gamma and IL-12p40 was decreased. Treatment with the antioxidant N
      acetylcysteine did not affect diesel-enhanced virus titers but blocked the DE
      induced changes in cytokine profiles and lung inflammation. We conclude that
      exposure to DE during an influenza infection polarizes the local immune responses
      to an IL-4 dominated profile in association with increased viral disease, and
      some aspects of this effect can be reversed with antioxidants.

PMID- 21092163
TI  - Evaluation of volumetric modulated arc therapy (VMAT) with Oncentra MasterPlan(r)
      for the treatment of head and neck cancer.
AB  - BACKGROUND: Several comparison studies have shown the capability of VMAT to
      achieve similar or better plan quality as IMRT, while reducing the treatment
      time. The experience of VMAT in a multi vendor environment is limited. We
      compared the plan quality and performance of VMAT to IMRT and we investigate the
      effects of varying various user-selectable parameters. METHODS: IMRT, single arc
      VMAT and dual arc VMAT were compared for four different head-and-neck tumors. For
      VMAT, the effect of varying gantry angle spacing and treatment time on the plan
      quality was investigated. A comparison of monitor units and treatment time was
      performed. RESULTS: IMRT and dual arc VMAT achieved a similar plan quality, while
      single arc could not provide an acceptable plan quality. Increasing the number of
      control points does not improve the plan quality. Dual arc VMAT delivery time is
      about 30% of IMRT delivery time. CONCLUSIONS: Dual arc VMAT is a fast and
      accurate technique for the treatment of head and neck cancer. It applies similar
      number of MUs as IMRT, but the treatment time is strongly reduced, maintaining
      similar or better dose conformity to the PTV and OAR sparing.

PMID- 21092164
TI  - Disseminating research findings: what should researchers do? A systematic scoping
      review of conceptual frameworks.
AB  - BACKGROUND: Addressing deficiencies in the dissemination and transfer of research
      based knowledge into routine clinical practice is high on the policy agenda both
      in the UK and internationally.However, there is lack of clarity between funding
      agencies as to what represents dissemination. Moreover, the expectations and
      guidance provided to researchers vary from one agency to another. Against this
      background, we performed a systematic scoping to identify and describe any
      conceptual/organising frameworks that could be used by researchers to guide their
      dissemination activity. METHODS: We searched twelve electronic databases
      (including MEDLINE, EMBASE, CINAHL, and PsycINFO), the reference lists of
      included studies and of individual funding agency websites to identify potential
      studies for inclusion. To be included, papers had to present an explicit
      framework or plan either designed for use by researchers or that could be used to
      guide dissemination activity. Papers which mentioned dissemination (but did not
      provide any detail) in the context of a wider knowledge translation framework,
      were excluded. References were screened independently by at least two reviewers;
      disagreements were resolved by discussion. For each included paper, the source,
      the date of publication, a description of the main elements of the framework, and
      whether there was any implicit/explicit reference to theory were extracted. A
      narrative synthesis was undertaken. RESULTS: Thirty-three frameworks met our
      inclusion criteria, 20 of which were designed to be used by researchers to guide
      their dissemination activities. Twenty-eight included frameworks were underpinned
      at least in part by one or more of three different theoretical approaches, namely
      persuasive communication, diffusion of innovations theory, and social marketing.
      CONCLUSIONS: There are currently a number of theoretically-informed frameworks
      available to researchers that can be used to help guide their dissemination
      planning and activity. Given the current emphasis on enhancing the uptake of
      knowledge about the effects of interventions into routine practice, funders could
      consider encouraging researchers to adopt a theoretically-informed approach to
      their research dissemination.

PMID- 21092165
TI  - Interface of culture, insecurity and HIV and AIDS: Lessons from displaced
      communities in Pader District, Northern Uganda.
AB  - BACKGROUND: Northern Uganda unlike other rural regions has registered high HIV
      prevalence rates comparable to those of urbanized Kampala and the central region.
      This could be due to the linkages of culture, insecurity and HIV. We explored
      community perceptions of HIV and AIDS as a problem and its inter-linkage with
      culture and insecurity in Pader District. METHODS: A cross sectional qualitative
      study was conducted in four sub-counties of Pader District, Uganda between May
      and June 2008. Data for the study were collected through 12 focus group
      discussions (FGDs) held separately; 2 FGDs with men, 6 FGDs with women, and 4
      FGDs with the youth (2 for each sex). In addition we conducted 15 key informant
      interviews with; 3 health workers, 4 community leaders at village and parish
      levels, 3 persons living with HIV and 5 district officials. Data were analysed
      using the content thematic approach. This process involved identification of the
      study themes and sub-themes following multiple reading of interview and
      discussion transcripts. Relevant quotations per thematic area were identified and
      have been used in the presentation of study findings. RESULTS: The struggles to
      meet the basic and survival needs by individuals and households overshadowed HIV
      as a major community problem. Conflict and risky sexual related cultural
      practices were perceived by communities as major drivers of HIV and AIDS in the
      district. Insecurity had led to congestion in the camps leading to moral
      decadence, rape and defilement, prostitution and poverty which increased
      vulnerability to HIV infection. The cultural drivers of HIV and AIDS were; widow
      inheritance, polygamy, early marriages, family expectations, silence about sex
      and alcoholism. CONCLUSIONS: Development partners including civil society
      organisations, central government, district administration, religious and
      cultural leaders as well as other stakeholders should mainstream HIV in all
      community development and livelihood interventions in the post conflict Pader
      district to curtail the likely escalation of the HIV epidemic. A comprehensive
      behaviour change communication strategy is urgently needed to address the
      negative cultural practices. Real progress in the region lies in advocacy and
      negotiation to realise lasting peace.

PMID- 21092166
TI  - Classification of root canal microorganisms using electronic-nose and
      discriminant analysis.
AB  - BACKGROUND: Root canal treatment is a debridement process which disrupts and
      removes entire microorganisms from the root canal system. Identification of
      microorganisms may help clinicians decide on treatment alternatives such as using
      different irrigants, intracanal medicaments and antibiotics. However, the
      difficulty in cultivation and the complexity in isolation of predominant
      anaerobic microorganisms make clinicians resort to empirical medical treatments.
      For this reason, identification of microorganisms is not a routinely used
      procedure in root canal treatment. In this study, we aimed at classifying 7
      different standard microorganism strains which are frequently seen in root canal
      infections, using odor data collected using an electronic nose instrument.
      METHOD: Our microorganism odor data set consisted of 5 repeated samples from 7
      different classes at 4 concentration levels. For each concentration, 35 samples
      were classified using 3 different discriminant analysis methods. In order to
      determine an optimal setting for using electronic-nose in such an application, we
      have tried 3 different approaches in evaluating sensor responses. Moreover, we
      have used 3 different sensor baseline values in normalizing sensor responses.
      Since the number of sensors is relatively large compared to sample size, we have
      also investigated the influence of two different dimension reduction methods on
      classification performance. RESULTS: We have found that quadratic type
      discriminant analysis outperforms other varieties of this method. We have also
      observed that classification performance decreases as the concentration
      decreases. Among different baseline values used for pre-processing the sensor
      responses, the model where the minimum values of sensor readings in the sample
      were accepted as the baseline yields better classification performance.
      Corresponding to this optimal choice of baseline value, we have noted that among
      different sensor response model and feature reduction method combinations, the
      difference model with standard deviation based dimension reduction or normalized
      fractional difference model with principal component analysis based dimension
      reduction results in the best overall performance across different
      concentrations. CONCLUSION: Our results reveal that the electronic nose
      technology is a promising and convenient alternative for classifying
      microorganisms that cause root canal infections. With our comprehensive approach,
      we have also determined optimal settings to obtain higher classification
      performance using this technology and discriminant analysis.

PMID- 21092167
TI  - Paramedics' and pre-hospital physicians' assessments of anatomic injury in trauma
      patients: a cohort study.
AB  - BACKGROUND: The pre-hospital assessment of a blunt trauma is difficult. Common
      triage tools are the mechanism of injury (MOI), vital signs, and anatomic injury
      (AI). Compared to the other tools, the clinical assessment of anatomic injury is
      more subjective than the others, and, hence, more dependent on the skills of the
      personnel.The aim of the study was to estimate whether the training and
      qualifications of the personnel are associated with the accuracy of prediction of
      anatomic injury and the completion of pre-hospital procedures indicated by local
      guidelines. METHODS: Adult trauma patients met by a trauma team at Helsinki
      University Trauma Centre during a 12-month period (n = 422) were retrospectively
      analysed. To evaluate the accuracy of prediction of anatomic injury, clinically
      assessed pre-hospital injuries in six body regions were compared to injuries
      assessed at hospital in two patient groups, the patients treated by pre-hospital
      physicians (group 1, n = 230) and those treated by paramedics (group 2, n = 190).
      RESULTS: The groups were comparable in respect to age, sex, and MOI, but the
      patients treated by physicians were more severely injured than those treated by
      paramedics [ISS median (interquartile range) 16 (6-26) vs. 6 (2-10)], thus
      rendering direct comparison of the groups ineligible. The positive predictive
      values (95% confidence interval) of assessed injury were highest in head injury
      [0,91 (0,84-0,95) in group 1 and 0,86 (0,77-0,92) in group 2]. The negative
      predictive values were highest in abdominal injury [0,85 (0,79-0,89) in group 1
      and 0,90 (0,84-0,93) in group 2]. The measurements of agreement between injuries
      assessed pre- and in-hospitally were moderate in thoracic and extremity injuries.
      Substantial kappa values (95% confidence interval) were achieved in head injury,
      0,67 (0,57-0,77) in group 1 and 0,63 (0,52-0,74) in group 2. The rate of
      performing the pre-hospital procedures as indicated by the local instructions was
      95-99%, except for decompression of tension pneumothorax. CONCLUSION: Accurate
      prediction of anatomic injury is challenging. No conclusive differences were seen
      in the ability of pre-hospital physicians and paramedics to predict anatomic
      injury in the respective patient populations.

PMID- 21092168
TI  - Reasons for illicit drug use in people with schizophrenia: Qualitative study.
AB  - BACKGROUND: Drug misuse is an important clinical problem associated with a poorer
      outcome in patients who have a diagnosis of schizophrenia. Qualitative studies
      have rarely been used to elicit reasons for drug use in psychosis, but not in
      schizophrenia. METHODS: Seventeen people with a diagnosis of schizophrenia and
      who had used street drugs were interviewed and asked to describe, in narrative
      form, their street drug use from their early experiences to the present day.
      Grounded theory was used to analyse the transcripts. RESULTS: We identified five
      reasons for continuing street drug use. The reasons were: as an 'identity
      defining vocation', 'to belong to a peer group', due to 'hopelessness', because
      of 'beliefs about symptoms and how street drugs influence them' and viewing drugs
      as 'equivalent to taking psychotropic medication'. Street drugs were often used
      to reduce anxiety aroused by voice hearing. Some participants reported street
      drugs to focus their attention more on persecutory voices in the hope of
      outwitting their perceived persecutors. CONCLUSIONS: It would be clinically
      useful to examine for the presence of the five factors in patients who have a
      diagnosis of schizophrenia and use street drugs, as this is likely to help the
      clinician to tailor management of substance misuse to the individual patient's
      beliefs.

PMID- 21092169
TI  - Epstein-Barr virus infection and chronic lymphocytic leukemia: a possible
      progression factor?
AB  - Epstein-Barr virus is pathogenically associated with a well defined group of
      lymphoid and epithelial tumors in which the virus directly drives transformation
      of infected cells. Recent evidence however indicates that this virus may infect a
      subpopulation of tumor cells in patients with chronic lymphocytic leukemia (CLL)
      and EBV infection has been also associated with Richter transformation in a
      fraction of cases. We herein review available data suggesting a possible role of
      EBV as a direct or micro-environmental progression factor in a subset of CLL.

PMID- 21092170
TI  - Imprinted genes show unique patterns of sequence conservation.
AB  - BACKGROUND: Genomic imprinting is an evolutionary conserved mechanism of
      epigenetic gene regulation in placental mammals that results in silencing of one
      of the parental alleles. In order to decipher interactions between allele
      specific DNA methylation of imprinted genes and evolutionary conservation, we
      performed a genome-wide comparative investigation of genomic sequences and highly
      conserved elements of imprinted genes in human and mouse. RESULTS: Evolutionarily
      conserved elements in imprinted regions differ from those associated with
      autosomal genes in various ways. Whereas for maternally expressed genes strong
      divergence of protein-encoding sequences is most prominent, paternally expressed
      genes exhibit substantial conservation of coding and noncoding sequences.
      Conserved elements in imprinted regions are marked by enrichment of CpG
      dinucleotides and low (TpG+CpA)/(2.CpG) ratios indicate reduced CpG deamination.
      Interestingly, paternally and maternally expressed genes can be distinguished by
      differences in G+C and CpG contents that might be associated with unusual
      epigenetic features. Especially noncoding conserved elements of paternally
      expressed genes are exceptionally G+C and CpG rich. In addition, we confirmed a
      frequent occurrence of intronic CpG islands and observed a decelerated
      degeneration of ancient LINE-1 repeats. We also found a moderate enrichment of
      YY1 and CTCF binding sites in imprinted regions and identified several short
      sequence motifs in highly conserved elements that might act as additional
      regulatory elements. CONCLUSIONS: We discovered several novel conserved DNA
      features that might be related to allele-specific DNA methylation. Our results
      hint at reduced CpG deamination rates in imprinted regions, which affects mostly
      noncoding conserved elements of paternally expressed genes. Pronounced
      differences between maternally and paternally expressed genes imply specific
      modes of evolution as a result of differences in epigenetic features and a
      special response to selective pressure. In addition, our data support the
      potential role of intronic CpG islands as epigenetic key regulatory elements and
      suggest that evolutionary conserved LINE-1 elements fulfill regulatory functions
      in imprinted regions.

PMID- 21092171
TI  - Self monitoring of blood glucose - a survey of diabetes UK members with type 2
      diabetes who use SMBG.
AB  - BACKGROUND: Aim - to survey members of Diabetes UK who had Type 2 diabetes and
      who used self monitoring of blood glucose (SMBG), to elicit their views on its
      usefulness in the management of their diabetes, and how they used the results. A
      questionnaire was developed for the Diabetes UK website. The questionnaire was
      posted on the Diabetes UK website until over 500 people had responded. Questions
      asked users to specify the benefits gained from SMBG, and how these benefits were
      achieved. We carried out both quantitative analysis and a thematic analysis for
      the open ended free-text questions. FINDINGS: 554 participants completed the
      survey, of whom 289 (52.2%) were male. 20% of respondents were recently diagnosed
      (< 6 months). Frequency of SMBG varied, with 43% of participants testing between
      once and four times a day and 22% testing less than once a month or for
      occasional periods.80% of respondents reported high satisfaction with SMBG, and
      reported feeling more 'in control' of their diabetes management using it. The
      most frequently reported use of SMBG was to make adjustments to food intake or
      confirm a hyperglycaemic episode.Women were significantly more likely to report
      feelings of guilt or self-chastisement associated with out of range readings (p =
      < .001). CONCLUSION: SMBG was clearly of benefit to this group of confirmed
      users, who used the results to adjust diet, physical activity or medications.
      However many individuals (particularly women) reported feelings of anxiety and
      depression associated with its use.

PMID- 21092172
TI  - Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to
      human epithelium cell carcinoma.
AB  - BACKGROUND: To identify new and useful candidate biomarkers in head and neck
      squamous cell carcinoma (HNSCC), we performed a genome-wide survey and found that
      Myelin and lymphocyte-associated protein (MAL) was a gene that was markedly down
      regulated in HNSCC. Hence, we investigated the mechanism of MAL silencing and the
      effects of MAL on the proliferation, invasion, and apoptotic potential in HNSCC.
      RESULTS: MAL was significantly down-regulated in 91.7% of HNSCC specimens at the
      mRNA level as compared with adjacent normal tissues (P = 0.0004). Moreover, the
      relative transcript levels of the MAL gene were remarkably decreased by five-fold
      in nine HNSCC cell lines as compared with normal head and neck epithelium cells.
      MAL gene expression was restored in 44%, 67%, and 89% in HNSCC cell lines treated
      with TSA, 5-Aza-dC, and TSA plus 5-Aza-dC, respectively. Furthermore, bisulfate
      treated DNA sequencing demonstrated that the two CpG islands (that is, M1 and M2)
      located in MAL promoter region were completely methylated in the HNSCC cell lines
      (CpG methylated ratio was more than 90%), and only one CpG island (that is, M1)
      was partially methylated in HNSCC tissues (CpG methylated ratio between 20% and
      90%). A significant reduction in cell proliferation and a change in the cell
      cycle profile were also observed in MAL transfectants. Matrigel assay
      demonstrated that the invasiveness of HNSCC cells significantly decreased. A
      significant increase in the population of apoptotic cells was observed in MAL
      transfected cells. The exogenous expression of the MAL gene suppressed malignant
      phenotypes, while the cell death induced by MAL gene transfer was a result of
      apoptosis as demonstrated by the induction of cleavage of the poly (that is, ADP
      ribose) polymerase. Additionally, tumor growth was suppressed in cells expressing
      MAL as compared with cells not expressing MAL. CONCLUSION: Our data suggest that
      the epigenetic inactivation of MAL, as a candidate tumor suppressor gene, can
      contribute to human epithelial cell carcinoma and may be served as a biomarker in
      HNSCC.

PMID- 21092173
TI  - Transarticular screw fixation for atlantoaxial instability - modified Magerl's
      technique in 38 patients.
AB  - BACKGROUND: Symptomatic atlantoaxial instability needs stabilization of the
      atlantoaxial joint. Among the various techniques described in literature for the
      fixation of atlantoaxial joint, Magerl's technique of transarticular screw
      fixation remains the gold standard. Traditionally this technique combines
      placement of transarticular screws and posterior wiring construct. The aim of
      this study is to evaluate clinical and radiological outcomes in subjects of
      atlantoaxial instability who were operated using transarticular screws and iliac
      crest bone graft, without the use of sublaminar wiring (a modification of
      Magerl's technique). METHODS: We evaluated retrospectively 38 subjects with
      atlantoaxial instability who were operated at our institute using transarticular
      screw fixation. The subjects were followed up for pain, fusion rates,
      neurological status and radiographic outcomes. Final outcome was graded both
      subjectively and objectively, using the scoring system given by Grob et al.
      RESULTS: Instability in 34 subjects was secondary to trauma, in 3 due to
      rheumatoid arthritis and 1 had tuberculosis. Neurological deficit was present in
      17 subjects. Most common presenting symptom was neck pain, present in 35 of the
      38 subjects.Postoperatively residual neck and occipital pain was present in 8
      subjects. Neurological deficit persisted in only 7 subjects. Vertebral artery
      injury was seen in 3 subjects. None of these subjects had any sign of
      neurological deficit or vertebral insufficiency. Three cases had nonunion. At the
      latest follow up, subjectively, 24 subjects had good result, 6 had fair and 8 had
      bad result. On objective grading, 24 had good result, 11 had fair and 3 had bad
      result. The mean follow up duration was 41 months. CONCLUSIONS: Transarticular
      screw fixation is an excellent technique for fusion of the atlantoaxial complex.
      It provides highest fusion rates, and is particularly important in subjects at
      risk for nonunion. Omitting the posterior wiring construct that has been used
      along with the bone graft in the traditional Magerl' s technique achieves equally
      good fusion rates and is an important modification, thereby avoiding the
      complications of sublaminar wire passage.

PMID- 21092174
TI  - Impact of gamma-chain cytokines on EBV-specific T cell cultures.
AB  - BACKGROUND: Recent preclinical adoptive immunotherapy studies in murine models
      prompt to employ "proper" rather than "as many as possible" antigen-specific T
      cells to gain better therapeutic results. Ideally, "proper" T cells are poorly
      differentiated in vitro, but retain the capacity to fully differentiate into
      effector cells in vivo, where they can undergo long-term survival and strong
      proliferation. Such requirements can be achieved by modifying culture conditions,
      namely using less "differentiating" cytokines than IL-2. METHODS: To evaluate
      this issue in human T cell cultures, we exploited a well characterized and
      clinical-grade protocol finalized at generating EBV-specific CTL for adoptive
      immunotherapy. In particular, we studied the impact of IL-7, IL-15 and IL-21
      compared to IL-2 on different aspects of T cell functionality, namely growth
      kinetics, differentiation/activation marker expression, cytokine production, and
      short-term and long-term cytotoxicity. RESULTS: Results disclosed that the
      culture modifications we introduced in the standard protocol did not improve
      activity nor induce substantial changes in differentiation marker expression of
      EBV-specific CTL. CONCLUSIONS: Our data indicated that the addition of gamma
      chain cytokines other than IL-2 for the generation of EBV-specific T cell
      cultures did not produce the improvements expected on the basis of recent
      published literature. This fact was likely due to the intrinsic differences
      between murine and human models and highlights the need to design ad hoc
      protocols rather than simply modify the cytokines added in culture.

PMID- 21092175
TI  - High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in
      chronic fatigue syndrome.
AB  - BACKGROUND: Chocolate is rich in flavonoids that have been shown to be of benefit
      in disparate conditions including cardiovascular disease and cancer. The effect
      of polyphenol rich chocolate in subjects with chronic fatigue syndrome (CFS) has
      not been studied previously. METHODS: We conducted a double blinded, randomised,
      clinical pilot crossover study comparing high cocoa liquor/polyphenol rich
      chocolate (HCL/PR) in comparison to simulated iso-calorific chocolate (cocoa
      liquor free/low polyphenols(CLF/LP)) on fatigue and residual function in subjects
      with chronic fatigue syndrome. Subjects with CFS having severe fatigue of at
      least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had
      either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week
      wash out period followed by 8 weeks of intervention with the other chocolate.
      RESULTS: Ten subjects were enrolled in the study. The Chalder Fatigue Scale score
      improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range)
      Exact Sig. (2-tailed)] [33 (25 - 38) vs. 21.5 (6 - 35) 0.01], but that
      deteriorated significantly when subjects were given simulated iso-calorific
      chocolate (CLF/CP) [ 28.5 (17 - 20) vs. 34.5 (13-26) 0.03]. The residual
      function, as assessed by the London Handicap scale, also improved significantly
      after the HCL/PR arm [0.49 (0.33 - 0.62) vs. 0.64 (0.44 - 0.83) 0.01] and
      deteriorated after iso-calorific chocolate [00.44 (0.43 - 0.68) vs. 0.36 (0.33 -
      0.62)0.03]. Likewise the Hospital Anxiety and Depression score also improved
      after the HCL/PR arm, but deteriorated after CLF/CP. Mean weight remained
      unchanged throughout the trial. CONCLUSION: This study suggests that HCL/PR
      chocolate may improve symptoms in subjects with chronic fatigue syndrome.

PMID- 21092176
TI  - From fever to anti-malarial: the treatment-seeking process in rural Senegal.
AB  - BACKGROUND: Currently less than 15% of children under five with fever receive
      recommended artemisinin-combination therapy (ACT), far short of the Roll Back
      Malaria target of 80%. To understand why coverage remains low, it is necessary to
      examine the treatment pathway from a child getting fever to receiving appropriate
      treatment and to identify critical blockages. This paper presents the application
      of such a diagnostic approach to the coverage of prompt and effective treatment
      of children with fever in rural Senegal. METHODS: A two-stage cluster sample
      household survey was conducted in August 2008 in Tambacounda, Senegal, to
      investigate treatment behaviour for children under five with fever in the
      previous two weeks. The treatment pathway was divided in to five key steps; the
      proportion of all febrile children reaching each step was calculated. Results
      were stratified by sector of provider (public, community, and retail). Logistic
      regression was used to determine predictors of treatment seeking. RESULTS:
      Overall 61.6% (188) of caretakers sought any advice or treatment and 40.3% (123)
      sought any treatment promptly within 48 hours. Over 70% of children taken to any
      provider with fever did not receive an anti-malarial. The proportion of febrile
      children receiving ACT within 48 hours was 6.2% (19) from any source; inclusion
      of correct dose and duration reduced this to 1.3%. The proportion of febrile
      children receiving ACT within 48 hours (not including dose & duration) was 3.0%
      (9) from a public provider, 3.0% (9) from a community source and 0.3% (1) from
      the retail sector. Inclusion of confirmed diagnosis within the public sector
      treatment pathway as per national policy increases the proportion of children
      receiving appropriate treatment with ACT in this sector from 9.4% (9/96) to an
      estimated 20.0% (9/45). CONCLUSIONS: Process analysis of the treatment pathway
      for febrile children must be stratified by sector of treatment-seeking. In
      Tambacounda, Senegal, interventions are needed to increase prompt care-seeking
      for fever, improve uptake of rapid diagnostic tests at the public and community
      levels and increase correct treatment of parasite-positive patients with ACT.
      Limited impact will be achieved if interventions to improve prompt and effective
      treatment target only one step in the treatment pathway in any sector.

PMID- 21092177
TI  - A panel of kallikrein markers can predict outcome of prostate biopsy following
      clinical work-up: an independent validation study from the European Randomized
      Study of Prostate Cancer screening, France.
AB  - BACKGROUND: We have previously shown that a panel of kallikrein markers--total
      prostate-specific antigen (PSA), free PSA, intact PSA and human kallikrein
      related peptidase 2 (hK2)--can predict the outcome of prostate biopsy in men with
      elevated PSA. Here we investigate the properties of our panel in men subject to
      clinical work-up before biopsy. METHODS: We applied a previously published
      predictive model based on the kallikrein panel to 262 men undergoing prostate
      biopsy following an elevated PSA (>= 3 ng/ml) and further clinical work-up during
      the European Randomized Study of Prostate Cancer screening, France. The
      predictive accuracy of the model was compared to a "base" model of PSA, age and
      digital rectal exam (DRE). RESULTS: 83 (32%) men had prostate cancer on biopsy of
      whom 45 (54%) had high grade disease (Gleason score 7 or higher). Our model had
      significantly higher accuracy than the base model in predicting cancer (area
      under-the-curve [AUC] improved from 0.63 to 0.78) or high-grade cancer (AUC
      increased from 0.77 to 0.87). Using a decision rule to biopsy those with a 20% or
      higher risk of cancer from the model would reduce the number of biopsies by
      nearly half. For every 1000 men with elevated PSA and clinical indication for
      biopsy, the model would recommend against biopsy in 61 men with cancer, the
      majority (~80%) of whom would have low stage and low grade disease at diagnosis.
      CONCLUSIONS: In this independent validation study, the model was highly
      predictive of prostate cancer in men for whom the decision to biopsy is based on
      both elevated PSA and clinical work-up. Use of this model would reduce a large
      number of biopsies while missing few cancers.

PMID- 21092178
TI  - Home visits by neighborhood Mentor Mothers provide timely recovery from childhood
      malnutrition in South Africa: results from a randomized controlled trial.
AB  - BACKGROUND: Child and infant malnourishment is a significant and growing problem
      in the developing world. Malnourished children are at high risk for negative
      health outcomes over their lifespans. Philani, a paraprofessional home visiting
      program, was developed to improve childhood nourishment. The objective of this
      study is to evaluate whether the Philani program can rehabilitate malnourished
      children in a timely manner. METHODS: Mentor Mothers were trained to conduct home
      visits. Mentor Mothers went from house to house in assigned neighborhoods,
      weighed children age 5 and younger, and recruited mother-child dyads where there
      was an underweight child. Participating dyads were assigned in a 2:1 random
      sequence to the Philani intervention condition (n = 536) or a control condition
      (n = 252). Mentor Mothers visited dyads in the intervention condition for one
      year, supporting mothers' problem-solving around nutrition. All children were
      weighed by Mentor Mothers at baseline and three, six, nine and twelve month
      follow-ups. RESULTS: By three months, children in the intervention condition were
      five times more likely to rehabilitate (reach a healthy weight for their ages)
      than children in the control condition. Throughout the course of the study, 43%
      (n = 233 of 536) of children in the intervention condition were rehabilitated
      while 31% (n = 78 of 252) of children in the control condition were
      rehabilitated. CONCLUSIONS: Paraprofessional Mentor Mothers are an effective
      strategy for delivering home visiting programs by providing the knowledge and
      support necessary to change the behavior of families at risk.

PMID- 21092179
TI  - Rationale and methods of the cardiometabolic Valencian study (Escarval-Risk) for
      validation of risk scales in Mediterranean patients with hypertension, diabetes
      or dyslipidemia.
AB  - BACKGROUND: The Escarval-Risk study aims to validate cardiovascular risk scales
      in patients with hypertension, diabetes or dyslipidemia living in the Valencia
      Community, a European Mediterranean region, based on data from an electronic
      health recording system comparing predicted events with observed during 5 years
      follow-up study. METHODS/DESIGN: A cohort prospective 5 years follow-up study has
      been designed including 25000 patients with hypertension, diabetes and/or
      dyslipidemia attended in usual clinical practice. All information is registered
      in a unique electronic health recording system (ABUCASIS) that is the usual way
      to register clinical practice in the Valencian Health System (primary and
      secondary care). The system covers about 95% of population (near 5 million
      people). The system is linked with database of mortality register, hospital
      withdrawals, prescriptions and assurance databases in which each individual have
      a unique identification number. Diagnoses in clinical practice are always
      registered based on IDC-9. Occurrence of CV disease was the main outcomes of
      interest. Risk survival analysis methods will be applied to estimate the
      cumulative incidence of developing CV events over time. DISCUSSION: The Escarval
      Risk study will provide information to validate different cardiovascular risk
      scales in patients with hypertension, diabetes or dyslipidemia from a low risk
      Mediterranean Region, the Valencia Community.

PMID- 21092180
TI  - Reciprocity between abscisic acid and ethylene at the onset of berry ripening and
      after harvest.
AB  - BACKGROUND: The ripening of grape berry is generally regulated by abscisic acid
      (ABA), and has no relationship with ethylene function. However, functional
      interaction and synergism between ABA and ethylene during the beginning of grape
      berry ripening (veraison) has been found recently. RESULTS: The expressions of
      VvNCED1 encoding 9-cis-epoxycarotenoid dioxygenase (NCED) and VvGT encoding ABA
      glucosyltransferase were all increased rapidly at the stage of veraison and
      reached the highest level at 9th week after full bloom. However, VvCYP1 encoding
      ABA 8'-hydroxylase and VvbetaG1 encoding berry beta-glucosidase are different,
      whose expression peak appeared at the 10th week after full bloom and in especial
      VvbetaG1 remained at a high level till harvest. The VvACO1 encoding 1
      aminocyclopropane-1-carboxylic acid (ACC) oxidase, the VvETR2 (ethylene response
      2) and VvCTR1 (constitutive triple response 1) had a transient expression peak at
      pre-veraison, while the VvEIN4 (ethylene insensitive 4) expression gradually
      increased from the veraison to one week before harvest stage. The above mentioned
      changes happened again in the berry after harvest. At one week before veraison,
      double block treatment with NiCl2 plus 1-methylcyclopropene (1-MCP) not only
      inhibited the release of ethylene and the expression of related genes but also
      suppressed the transcription of VvNCED1 and the synthesis of ABA which all might
      result in inhibiting the fruit ripening onset. Treatment with ABA could relieve
      the double block and restore fruit ripening course. However, after harvest,
      double block treatment with NiCl2 plus 1-MCP could not suppress the transcription
      of VvNCED1 and the accumulation of ABA, and also could not inhibit the start of
      fruit senescence. CONCLUSION: The trace endogenous ethylene induces the
      transcription of VvNCED1 and then the generation of ABA followed. Both ethylene
      and ABA are likely to be important and their interplaying may be required to
      start the process of berry ripening. When the level of ABA reached the peak
      value, part of it will be stored in the form of ABA-GE. While after harvest,
      abiotic stresses principally (such as dehydration, harvest shock) could induce
      the transcription of VvNCED1 and the accumulation of ABA, thus starting the
      process of fruit senescence.

PMID- 21092181
TI  - Early detection of urothelial premalignant lesions using hexaminolevulinate
      fluorescence cystoscopy in high risk patients.
AB  - BACKGROUND: To evaluate fluorescence cystoscopy with hexaminolevulinate (HAL) in
      the early detection of dysplasia (DYS) and carcinoma in situ (CIS) in select high
      risk patients. METHODS: We selected 30 consecutive bladder cancer patients at
      high risk for progression. After endoscopic resection, all patients received (a)
      induction BCG schedule when needed, and (b) white light and fluorescence
      cystoscopy after 3 months. HAL at doses of 85 mg (GE Healthcare, Buckinghamshire,
      United Kingdom) dissolved in 50 ml of solvent to obtain an 8 mmol/L solution was
      instilled intravesically with a 12 Fr catheter into an empty bladder and left for
      90 minutes. The solution was freshly prepared immediately before instillation.
      Cystoscopy was performed within 120 minutes of bladder emptying. Standard and
      fluorescence cystoscopy was performed using a double light system (Combilight PDD
      light source 5133, Wolf, Germany) which allowed an inspection under both white
      and blue light. RESULTS: The overall incidence was 43.3% dysplasia, 23.3% CIS,
      and 13.3% superficial transitional cell cancer. In 21 patients, HAL cystoscopy
      was positive with one or more fluorescent flat lesions. Of the positive cases,
      there were 4 CIS, 10 DYS, 2 association of CIS and DYS, 4 well-differentiated non
      infiltrating bladder cancers, and 1 chronic cystitis. In 9 patients with negative
      HAL results, random biopsies showed 1 CIS and 1 DYS. HAL cystoscopy showed 90.1%
      sensitivity and 87.5% specificity with 95.2% positive predictive value and 77.8%
      negative predictive value. CONCLUSION: Photodynamic diagnosis should be
      considered a very important tool in the diagnosis of potentially evolving flat
      lesions on the bladder mucosa such as DYS and CIS. Moreover, detection of
      dysplasic lesions that are considered precursors of CIS may play an important
      role in preventing disease progression. In our opinion, HAL cystoscopy should be
      recommended in the early follow-up of high risk patients.

PMID- 21092182
TI  - Lipid control and use of lipid-regulating drugs for prevention of cardiovascular
      events in Chinese type 2 diabetic patients: a prospective cohort study.
AB  - BACKGROUND: Dyslipidaemia is an important but modifiable risk factor of
      cardiovascular disease (CVD) in type 2 diabetes. Yet, the effectiveness of lipid
      regulating drugs in Asians is lacking. We examined the effects of lipid control
      and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2
      diabetic patients. METHODS: In this prospective cohort consisting of 4521 type 2
      diabetic patients without history of CVD and naive for lipid regulating treatment
      recruited consecutively from 1996 to 2005, 371 developed CVD after a median
      follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the
      hazard ratios (HR) of lipids and use of lipid regulating drugs for risk of CVD.
      RESULTS: The multivariate-adjusted HR (95% confidence interval) of CVD in
      patients with high LDL-cholesterol (>= 3.0 mmol/L) was 1.36 (1.08 - 1.71),
      compared with lower values. Using the whole range value of HDL-cholesterol, the
      risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol.
      Plasma triglyceride did not predict CVD. Statins use was associated with lower
      CVD risk [HR = 0.66 (0.50 - 0.88)]. In sub-cohort analysis, statins use was
      associated with a HR of 0.60 (0.44 - 0.82) in patients with high LDL-cholesterol
      (>= 3.0 mmol/L) and 0.49 (0.28 - 0.88) in patients with low HDL-cholesterol. In
      patients with LDL-cholesterol < 3.0 mmol/L, use of fibrate was associated with HR
      of 0.34 (0.12 - 1.00). Only statins were effective in reducing incident CVD in
      patients with metabolic syndrome [(HR = 0.58(0.42 - 0.80)]. CONCLUSIONS: In
      Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol
      predicted incident CVD. Overall, patients treated with statins had 40-50% risk
      reduction in CVD compared to non-users.

PMID- 21092183
TI  - Antenatal counseling in maternal and newborn care: use of job aids to improve
      health worker performance and maternal understanding in Benin.
AB  - BACKGROUND: Antenatal care provides an important opportunity to improve maternal
      understanding of care during and after pregnancy. Yet, studies suggest that
      communication is often insufficient. This research examined the effect of a job
      aids-focused intervention on quality of counseling and maternal understanding of
      care for mothers and newborns. METHODS: Counseling job aids were developed to
      support provider communication to pregnant women. Fourteen health facilities were
      randomized to control or intervention, where providers were trained to use job
      aids and provided implementation support. Direct observation of antenatal
      counseling sessions and patient exit interviews were undertaken to assess quality
      of counseling and maternal knowledge. Providers were also interviewed regarding
      their perceptions of the tools. Data were collected before and after the job aids
      intervention and analyzed using a difference-in-differences analysis to quantify
      relative changes over time. RESULTS: Mean percent of recommended messages
      provided to pregnant women significantly improved in the intervention arm as
      compared to the control arm in birth preparedness (difference-in-differences
      [DeltaI-C] = +17.9, 95%CI: 6.7,29.1), danger sign recognition (DeltaI-C = +26.0,
      95%CI: 14.6,37.4), clean delivery (DeltaI-C = +21.7, 95%CI: 10.9,32.6), and
      newborn care (DeltaI-C = +26.2, 95%CI: 13.5,38.9). Significant gains were also
      observed in the mean percent of communication techniques applied (DeltaI-C =
      +28.8, 95%CI: 22.5,35.2) and duration (minutes) of antenatal consultations
      (DeltaI-C = +5.9, 95%CI: 3.0,8.8). No relative increase was found for messages
      relating to general prenatal care (DeltaI-C = +8.2, 95%CI: -2.6,19.1). The
      proportion of pregnant women with correct knowledge also significantly improved
      for birth preparedness (DeltaI-C = +23.6, 95%CI: 9.8,37.4), danger sign
      recognition (DeltaI-C = +28.7, 95%CI: 14.2,43.2), and clean delivery (DeltaI-C =
      +31.1, 95%CI: 19.4,42.9). There were no significant changes in maternal knowledge
      of general prenatal (DeltaI-C = -6.4, 95%CI: -21.3,8.5) or newborn care (DeltaI-C
      = +12.7, 95%CI: -6.1,31.5). Job aids were positively perceived by providers and
      pregnant women, although time constraints remained for health workers with other
      clinical responsibilities. CONCLUSIONS: This study demonstrates that a job aids
      focused intervention can be integrated into routine antenatal care with positive
      outcomes on provider communication and maternal knowledge. Efforts are needed to
      address time constraints and other communication barriers, including introduction
      of on-going quality assessment for long-term sustainability.

PMID- 21092184
TI  - Acetylated microtubules are required for fusion of autophagosomes with lysosomes.
AB  - BACKGROUND: Autophagy is a dynamic process during which isolation membranes
      package substrates to form autophagosomes that are fused with lysosomes to form
      autolysosomes for degradation. Although it is agreed that the LC3II-associated
      mature autophagosomes move along microtubular tracks, it is still in dispute if
      the conversion of LC3I to LC3II before autophagosomes are fully mature and
      subsequent fusion of mature autophagosomes with lysosomes require microtubules.
      RESULTS: We use biochemical markers of autophagy and a collection of microtubule
      interfering reagents to test the question. Results show that interruption of
      microtubules with either microtubule stabilizing paclitaxel or destabilizing
      nocodazole similarly impairs the conversion of LC3I to LC3II, but does not block
      the degradation of LC3II-associated autophagosomes. Acetylation of microtubules
      renders them resistant to nocodazole treatment. Treatment with vinblastine that
      causes depolymerization of both non-acetylated and acetylated microtubules
      results in impairment of both LC3I-LC3II conversion and LC3II-associated
      autophagosome fusion with lysosomes. CONCLUSIONS: Acetylated microtubules are
      required for fusion of autophagosomes with lysosomes to form autolysosomes.

PMID- 21092185
TI  - Role of the atypical chemoattractant receptor CRAM in regulating CCL19 induced
      CCR7 responses in B-cell chronic lymphocytic leukemia.
AB  - BACKGROUND: The non-signalling chemokine receptors, including receptors DARC, D6
      and CCX-CKR, have recently been shown to be involved in chemokine clearance and
      activity regulation. The human chemokine receptor CRAM (also known as HCR or
      CCRL2) is the most recently identified member of this atypical group. CRAM is
      expressed on B cells in a maturation-stage dependent manner and absent on T
      cells. We have recently shown that it competitively binds CCL19. CCL19 and its
      signalling receptor CCR7 are critical components involved in cell recruitment to
      secondary lymphoid organs and in maturation. B cell Chronic Lymphocytic Leukemia
      (B-CLL) is a low-grade lymphoma characterized by proliferative centres (or
      pseudofollicles). Proliferative centres develop due to abnormal cellular
      localisation and they are involved in the development of malignant cells. CCR7 is
      highly expressed on B cells from CLL patients and mediates migration towards its
      ligands CCL19 and CCL21, while CRAM expression and potential interferences with
      CCR7 are yet to be characterized. RESULTS: In this study, we show that B cells
      from patients with B-CLL present highly variable degrees of CRAM expression in
      contrast to more consistently high levels of CCR7. We investigated the hypothesis
      that, similar to the atypical receptor DARC, CRAM can modulate chemokine
      availability and/or efficacy, resulting in the regulation of cellular activation.
      We found that a high level of CRAM expression was detrimental to efficient
      chemotaxis with CCL19. MAP-kinase phosphorylation and intracellular calcium
      release induced by CCL19 were also altered by CRAM expression. In addition, we
      demonstrate that CRAM-induced regulation of CCL19 signalling is maintained over
      time. CONCLUSIONS: We postulate that CRAM is a factor involved in the fine
      tuning/control of CCR7/CCL19 mediated responses. This regulation could be
      critical to the pivotal role of CCL19 induced formation of proliferation centres
      supporting the T/B cells encounter as well as disease progression in B-CLL.

PMID- 21092186
TI  - Polymorphisms in genes involved in the estrogen pathway and mammographic density.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes involved in the
      estrogen pathway appear to be associated with breast cancer risk and possibly
      with mammographic density (MD), but little is known of these associations among
      premenopausal women. This study examines the association of 11 polymorphisms in
      five estrogen-related genes (estrogen receptors alpha and beta (ERalpha, ERbeta),
      17beta-hydroxysteroid dehydrogenase 1 (HSD17B1), catechol-O-methyltransferase
      (COMT), cytochrome P450 1B1 (CYP1B1)) with premenopausal MD. Effect modification
      of four estrogen-related factors (parity, age at menarche, hormonal derivatives
      use and body mass index (BMI)) on this relation is also assessed. METHODS:
      Polymorphisms were genotyped in 741 premenopausal Caucasian women whose MD was
      measured in absolute density (AD, cm2) and percent density using a computer
      assisted method. Multivariate linear models were used to examine the associations
      (P(trend)) and interactions (Pi). RESULTS: None of the SNPs showed a
      statistically significant association with AD. However, each additional rare
      allele of rs1056836 CYP1B1 was associated with a reduction in AD among
      nulliparous women (P(trend) = 0.004), while no association was observed among
      parous women (P(trend) = 0.62; Pi = 0.02). An increase in the number of rare
      alleles of the HSD17B1 SNP (rs598126 and rs2010750) was associated with an
      increase in AD among women who never used hormonal derivatives (P(trend) = 0.06
      and P(trend) = 0.04, respectively), but with a decrease in AD among past hormonal
      derivatives users (P(trend) = 0.04; Pi = 0.02 and P(trend) = 0.08; Pi = 0.01,
      respectively). Moreover, a negative association of rs598126 HSD17B1 SNP with AD
      was observed among women with higher BMI (>median) (P(trend) = 0.01; Pi = 0.02).
      A negative association between an increased number of rare alleles of COMT rs4680
      SNP and AD was limited to women who never used hormonal derivatives (P(trend) =
      0.02; Pi = 0.03) or with late age at menarche (>median) (P(trend) = 0.03; Pi =
      0.02). No significant association was observed between polymorphisms in the
      ERalpha or ERbeta genes and AD. Similar results, although less significant, were
      observed when MD was assessed in percent density. CONCLUSION: SNPs located in
      CYP1B1, COMT or HSD17B1 genes seem to be associated with MD in some strata of
      estrogen-related factors. Our findings suggest that modifying effects of estrogen
      related factors should be considered when evaluating associations of
      polymorphisms in estrogen-related genes with premenopausal mammographic density.

PMID- 21092188
TI  - miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c
      Myc.
AB  - MicroRNAs are important gene regulators that potentially play a profound role in
      tumorigenesis. Increasing evidence indicates that miR-145 is a tumor suppressor
      capable of inhibiting breast and colon cancer cell growth both in vitro and in
      vivo. However, the biological function of miR-145 in non-small cell lung cancer
      (NSCLC) is largely unknown. In colon cancer cells, c-Myc is a confirmed direct
      target for miR-145. The aim of this work was to investigate the effect of miR-145
      and c-Myc on proliferation of NSCLC cells, using the NSCLC cell lines A549 and
      H23 as models. We determined the expression level of miR-145 in tumor tissues
      relative to adjacent non-tumor tissues, and in NSCLC cell lines relative to non
      malignant lung cells. Downregulation of miR-145 was seen in tumor tissues and the
      two NSCLC cell lines by real-time quantitative reverse transcription polymerase
      chain reaction. MTT and focus formation assays were conducted to measure cell
      proliferation rates. Cell growth was inhibited and the G1/S transition was
      blocked by miR-145 in transfection assays of A549 and H23 cells. We further
      showed that c-Myc was a direct target for miR-145. Introduction of miR-145
      dramatically suppressed the c-Myc/eIF4E pathway, which was demonstrated to be
      crucial for cell proliferation in NSCLC cells. Furthermore, we found that CDK4
      was regulated by miR-145 in cell cycle control. Taken together, our study results
      demonstrate that miR-145 inhibits proliferation of NSCLC cells through c-Myc.
      Increasing miR-145 expression may provide a novel approach for the treatment of
      NSCLC.

PMID- 21092189
TI  - Quality of Life as reported by children and parents: a comparison between
      students and child psychiatric outpatients.
AB  - BACKGROUND: During the recent decade, a number of studies have begun to address
      Quality of Life (QoL) in children and adolescents with mental health problems in
      general population and clinical samples. Only about half of the studies utilized
      both self and parent proxy report of child QoL. Generally children with mental
      health problems have reported lower QoL compared to healthy children. The
      question whether QoL assessment by both self and parent proxy report can identify
      psychiatric health services needs not detected by an established instrument for
      assessing mental health problems, i.e. the Child Behavior Checklist (CBCL), has
      never been examined and was the purpose of the present study. METHODS: No study
      exists that compares child QoL as rated by both child and parent, in a sample of
      referred child psychiatric outpatients with a representative sample of students
      attending public school in the same catchment area while controlling for mental
      health problems in the child. In the current study patients and students, aged 8
      15.5 years, were matched with respect to age, gender and levels of the CBCL Total
      Problems scores. QoL was assessed by the self- and parent proxy-reports on the
      Inventory of Life Quality in Children and Adolescents (ILC). QoL scores were
      analyzed by non-parametric tests, using Wilcoxon paired rank comparisons.
      RESULTS: Both outpatients and their parents reported significantly lower child
      QoL on the ILC than did students and their parents, when children were matched on
      sex and age. Given equal levels of emotional and behavioural problems, as
      reported by the parents on the CBCL, in the two contrasting samples, the
      outpatients and their parents still reported lower QoL levels than did the
      students and their parents. CONCLUSIONS: Child QoL reported both by child and
      parent was reduced in outpatients compared to students with equal levels of
      mental health problems as reported by their parents on the CBCL. This suggests
      that it should be helpful to add assessment of QoL to achieve a fuller picture of
      children presenting to mental health services.

PMID- 21092190
TI  - The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in
      combination with gemcitabine.
AB  - BACKGROUND: Sigma-2 receptors are over-expressed in proliferating cancer cells,
      making an attractive target for the targeted treatment of pancreatic cancer. In
      this study, we investigated the role of the novel sigma-2 receptor ligand SW43 to
      induce apoptosis and augment standard chemotherapy. RESULTS: The binding affinity
      for sigma-2 ligands is high in pancreas cancer, and they induce apoptosis with a
      rank order of SV119 < SW43 < SRM in vitro. Combining these compounds with
      gemcitabine further increased apoptosis and decreased viability. Our in vivo
      model showed that sigma-2 ligand treatment decreased tumor volume to the same
      extent as gemcitabine. However, SW43 combination treatment with gemcitabine was
      superior to the other compounds and resulted in stabilization of tumor volume
      during treatment, with minimal toxicities. CONCLUSIONS: This study shows that the
      sigma-2 ligand SW43 has the greatest capacity to augment gemcitabine in a pre
      clinical model of pancreas cancer and has provided us with the rationale to move
      this compound forward with clinical investigations for patients with pancreatic
      cancer.

PMID- 21092192
TI  - The reductase domain in a Type I fatty acid synthase from the apicomplexan
      Cryptosporidium parvum: restricted substrate preference towards very long chain
      fatty acyl thioesters.
AB  - BACKGROUND: The apicomplexan Cryptosporidium parvum genome possesses a 25-kb
      intronless open reading frame (ORF) that predicts a multifunctional Type I fatty
      acid synthase (CpFAS1) with at least 21 enzymatic domains. Although the
      architecture of CpFAS1 resembles those of bacterial polyketide synthases (PKSs),
      this megasynthase is predicted to function as a fatty acyl elongase as our
      earlier studies have indicated that the N-terminal loading unit (acyl-[ACP]
      ligase) prefers using intermediate to long chain fatty acids as substrates, and
      each of the three internal elongation modules contains a complete set of enzymes
      to produce a saturated fatty acyl chain. Although the activities of almost all
      domains were confirmed using recombinant proteins, that of the C-terminal
      reductase domain (CpFAS1-R) was yet undetermined. In fact, there were no
      published studies to report the kinetic features of any reductase domains in
      bacterial PKSs using purified recombinant or native proteins. RESULTS: In the
      present study, the identity of CpFAS1-R as a reductase is confirmed by in silico
      analysis on sequence similarity and characteristic motifs. Phylogenetic analysis
      based on the R-domains supports a previous notion on the bacterial origin of
      apicomplexan Type I FAS/PKS genes. We also developed a novel assay using fatty
      acyl-CoAs as substrates, and determined that CpFAS1-R could only utilize very
      long chain fatty acyl-CoAs as substrates (i.e., with activity on C26 > C24 > C22
      > C20, but no activity on C18 and C16). It was capable of using both NADPH and
      NADH as electron donors, but prefers NADPH to NADH. The activity of CpFAS1-R
      displayed allosteric kinetics towards C26 hexacosanoyl CoA as a substrate (h =
      2.0; Vmax = 32.8 nmol min-1 mg-1 protein; and K50 = 0.91 mM). CONCLUSIONS: We
      have confirmed the activity of CpFAS1-R by directly assaying its substrate
      preference and kinetic parameters, which is for the first time for a Type I FAS,
      PKS or non-ribosomal peptide synthase (NRPS) reductase domain. The restricted
      substrate preference towards very long chain fatty acyl thioesters may be an
      important feature for this megasynthase to avoid the release of product(s) with
      undesired lengths.

PMID- 21092193
TI  - Thymic large cell neuroendocrine carcinoma: report of a resected case - a case
      report.
AB  - Thymic large cell neuroendocrine carcinomas (LCNECs) are very rare. We here
      describe a case in which the tumor could be completely resected. A 55-year-old
      male was admitted to our hospital for treatment of an anterior mediastinal tumor
      found at a regular health check-up. The patient underwent an extended thymectomy
      of an invasive thymoma of Masaoka's stage II that had been suspected
      preoperatively. The tumor was located in the right lobe of the thymus and was
      completely resected. Final pathological diagnosis of the surgical specimen was
      thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and
      cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without
      recurrence or metastasis 16 months after surgery.

PMID- 21092191
TI  - The effect of post-discharge educational intervention on patients in achieving
      objectives in modifiable risk factors six months after discharge following an
      episode of acute coronary syndrome, (CAM-2 Project): a randomized controlled
      trial.
AB  - OBJECTIVES: We investigated whether an intervention mainly consisting of a signed
      agreement between patient and physician on the objectives to be reached, improves
      reaching these secondary prevention objectives in modifiable cardiovascular risk
      factors six-months after discharge following an acute coronary syndrome.
      BACKGROUND: There is room to improve mid-term adherence to clinical guidelines'
      recommendations in coronary heart disease secondary prevention, specially non
      pharmacological ones, often neglected. METHODS: In CAM-2, patients discharged
      after an acute coronary syndrome were randomly assigned to the intervention or
      the usual care group. The primary outcome was reaching therapeutic objectives in
      various secondary prevention variables: smoking, obesity, blood lipids, blood
      pressure control, exercise and taking of medication. RESULTS: 1757 patients were
      recruited in 64 hospitals and 1510 (762 in the intervention and 748 in the
      control group) attended the six-months follow-up visit. After adjustment for
      potentially important variables, there were, between the intervention and control
      group, differences in the mean reduction of body mass index (0.5 vs. 0.2; p <
      0.001) and waist circumference (1.6 cm vs. 0.6 cm; p = 0.05), proportion of
      patients who exercise regularly and those with total cholesterol below 175 mg/dl
      (64.7% vs. 56.5%; p = 0.001). The reported intake of medications was high in both
      groups for all the drugs considered with no differences except for statins (98.1%
      vs. 95.9%; p = 0.029). CONCLUSIONS: At least in the short term, lifestyle changes
      among coronary heart disease patients are achievable by intensifying the
      responsibility of the patient himself by means of a simple and feasible
      intervention.

PMID- 21092187
TI  - Fabry disease.
AB  - Fabry disease (FD) is a progressive, X-linked inherited disorder of
      glycosphingolipid metabolism due to deficient or absent lysosomal alpha
      galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1
      in 100,000 may underestimate the true prevalence of the disease. Classically
      affected hemizygous males, with no residual alpha-galactosidase A activity may
      display all the characteristic neurological (pain), cutaneous (angiokeratoma),
      renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia),
      cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes)
      signs of the disease while heterozygous females have symptoms ranging from very
      mild to severe. Deficient activity of lysosomal alpha-galactosidase A results in
      progressive accumulation of globotriaosylceramide within lysosomes, believed to
      trigger a cascade of cellular events. Demonstration of marked alpha-galactosidase
      A deficiency is the definitive method for the diagnosis of hemizygous males.
      Enzyme analysis may occasionnally help to detect heterozygotes but is often
      inconclusive due to random X-chromosomal inactivation so that molecular testing
      (genotyping) of females is mandatory. In childhood, other possible causes of pain
      such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood,
      multiple sclerosis is sometimes considered. Prenatal diagnosis, available by
      determination of enzyme activity or DNA testing in chorionic villi or cultured
      amniotic cells is, for ethical reasons, only considered in male fetuses. Pre
      implantation diagnosis is possible. The existence of atypical variants and the
      availability of a specific therapy singularly complicate genetic counseling. A
      disease-specific therapeutic option - enzyme replacement therapy using
      recombinant human alpha-galactosidase A - has been recently introduced and its
      long term outcome is currently still being investigated. Conventional management
      consists of pain relief with analgesic drugs, nephroprotection (angiotensin
      converting enzyme inhibitors and angiotensin receptors blockers) and
      antiarrhythmic agents, whereas dialysis or renal transplantation are available
      for patients experiencing end-stage renal failure. With age, progressive damage
      to vital organ systems develops and at some point, organs may start to fail in
      functioning. End-stage renal disease and life-threatening cardiovascular or
      cerebrovascular complications limit life-expectancy of untreated males and
      females with reductions of 20 and 10 years, respectively, as compared to the
      general population. While there is increasing evidence that long-term enzyme
      therapy can halt disease progression, the importance of adjunctive therapies
      should be emphasized and the possibility of developing an oral therapy drives
      research forward into active site specific chaperones.

PMID- 21092194
TI  - A neurotoxic regimen of methamphetamine exacerbates the febrile and
      neuroinflammatory response to a subsequent peripheral immune stimulus.
AB  - Methamphetamine (MA) use is associated with activation of microglia and, at high
      doses, can induce neurotoxicity. Given the changes in the neuroinflammatory
      environment associated with MA, we investigated whether MA administration would
      interfere with the thermoregulatory and neuroinflammatory response to a
      subsequent peripheral immune stimulus. C57BL6/J mice were given four i.p.
      injections of either 5 mg/kg MA or saline at two hour intervals. Twenty-four
      hours following the first MA injection, mice were given 100 MUg/kg LPS or saline
      i.p. and blood and brains were collected. Here we report that mice exposed to MA
      developed higher fevers in response to LPS than did those given LPS alone. MA
      also exacerbated the LPS-induced increase in central cytokine mRNA. MA alone
      increased microglial Iba1 expression and expression was further increased when
      mice were exposed to both MA and LPS, suggesting that MA not only activated
      microglia but also influenced their response to a peripheral immune stimulus.
      Taken together, these data show that MA administration exacerbates the normal
      central immune response, most likely by altering microglia.

PMID- 21092196
TI  - Unexpected elevated alanine aminotransferase, aspartate aminotransferase levels
      and hepatitis E virus infection among persons who work with pigs in accra, Ghana.
AB  - BACKGROUND: Several studies have suggested that elevated serum alanine
      aminotransferase (ALT) and asparte aminotransferase (AST) may be markers of
      hepatitis E virus (HEV) infection. Thus, individuals with elevated ALT and AST
      may have ongoing subclinical infection of HEV. We estimated the prevalence of
      anti-HEV antibodies and serum ALT and AST levels among persons who work with pigs
      in Accra, Ghana. RESULTS: Three hundred and fifty- persons who work with pigs
      provided blood samples for unlinked anonymous testing for the presence of
      antibodies to HEV, ALT and AST levels. The median age of participants was 32.85+/
      11.38 years (range 15-70 years). HEV seroprevelance was 34.84%. Anti-HEV IgG was
      detected in 19.26% while anti-HEV IgM was detected in 15.58% of the persons who
      tested positive. On multivariate analysis, the independent determinants of HEV
      infection were, being employed on the farm for less than six months [odds ratio
      (OR) 8.96; 95% confidence interval (95% CI) 5.43-14.80], having piped water in
      the household and/or on the farm (OR 13.33; 95% CI 5.23-33.93) and consumption of
      alcohol (OR 4.91: 95% CI 2.65-9.10). Levels>3* the expected maximum were found
      for both ALT and AST among individuals who tested positive for anti-HEV IgG (ALT,
      210.17+/-11.64 U/L; AST, 127.18+/-11.12 U/L) and anti-HEV IgM (ALT, 200.97+/
      10.76 U/L; AST, 120.00+/-15.96 U/L). CONCLUSION: Consistent with similar studies
      worldwide, the results of our studies revealed a high prevalence of HEV
      infection, ALT and AST values in pig handlers.

PMID- 21092195
TI  - Improving therapeutic HPV peptide-based vaccine potency by enhancing CD4+ T help
      and dendritic cell activation.
AB  - BACKGROUND: Effective vaccination against human papillomavirus (HPV) represents
      an opportunity to control cervical cancer. Peptide-based vaccines targeting HPV
      E6 and/or E7 antigens while safe, will most likely require additional strategies
      to enhance the vaccine potency. METHODS: We tested the HPV-16 E7 peptide-based
      vaccine in combination with a strategy to enhance CD4+ T help using a Pan HLA-DR
      epitope (PADRE) peptide and a strategy to enhance dendritic cell activation using
      the toll-like receptor 3 ligand, poly(I:C). RESULTS: We observed that mice
      vaccinated with E7 peptide-based vaccine in combination with PADRE peptide and
      poly(I:C) generated better E7-specific CD8+ T cell immune responses as well as
      significantly improved therapeutic anti-tumor effects against TC-1 tumors
      compared to E7 peptide-based vaccine with either PADRE peptide or poly(I:C)
      alone. Furthermore, we found that intratumoral vaccination with the E7 peptide in
      conjunction with PADRE peptide and poly(I:C) generates a significantly higher
      frequency of E7-specific CD8+ T cells as well as better survival compared to
      subcutaneous vaccination with the same regimen in treated mice. CONCLUSIONS: The
      combination of PADRE peptide and poly(I:C) with antigenic peptide is capable of
      generating potent antigen-specific CD8+ T cell immune responses and antitumor
      effects in vaccinated mice. Our study has significant clinical implications for
      peptide-based vaccination.

PMID- 21092197
TI  - Proteomic analysis of small acid soluble proteins in the spore core of Bacillus
      subtilis DeltaprpE and 168 strains with predictions of peptides liquid
      chromatography retention times as an additional tool in protein identification.
AB  - BACKGROUND: Sporulation, characteristic for some bacteria such as Bacillus
      subtilis, has not been entirely defined yet. Protein phosphatase E (PrpE) and
      small, acid soluble spore proteins (SASPs) influence this process. Nevertheless,
      direct result of PrpE interaction on SASPs content in spore coat of B. subtilis
      has not been evidenced so far. As proteomic approach enables global analysis of
      occurring proteins, therefore it was chosen in this experiment to compare SASPs
      occurrence in two strains of B. subtilis, standard 168 and DeltaprpE, lacking
      PrpE phosphatase. Proteomic analysis is still a challenge, and despite of big
      approach in mass spectrometry (MS) field, the identification reliability remains
      unsatisfactory. Therefore there is a rising interest in new methods, particularly
      bioinformatic tools that would harden protein identification. Most of currently
      applied algorithms are based on MS-data. Information from separation steps is not
      still in routine usage, even though they also provide valuable facts about
      analyzed structures. The aim of this research was to apply a model for peptides
      retention times prediction, based on quantitative structure-retention
      relationships (QSRR) in SASPs analysis, obtained from two strains of B. subtilis
      proteome digests after separation and identification of the peptides by LC-ESI
      MS/MS. The QSRR approach was applied as the additional constraint in proteomic
      research verifying results of MS/MS ion search and confirming the correctness of
      the peptides identifications along with the indication of the potential false
      positives and false negatives. RESULTS: In both strains of B. subtilis, peptides
      characteristic for SASPs were found, however their identification confidence
      varied. According to the MS identity parameter Xcorr and difference between
      predicted and experimental retention times (DeltatR) four groups could be
      distinguished: correctly and incorrectly identified, potential false positives
      and false negatives. The DeltaprpE strain was characterized by much higher amount
      of SASPs peptides than standard 168 and their identification confidence was,
      mostly for alpha- and beta-type SASP, satisfactory. CONCLUSIONS: The QSRR-based
      model for predicting retention times of the peptides, was a useful additional to
      MS tool, enhancing protein identification. Higher content of SASPs in strain
      lacking PrpE phosphatase suggests that this enzyme may influence their occurrence
      in the spores, lowering levels of these proteins.

PMID- 21092198
TI  - The use of communal rearing of families and DNA pooling in aquaculture genomic
      selection schemes.
AB  - BACKGROUND: Traditional family-based aquaculture breeding programs, in which
      families are kept separately until individual tagging and most traits are
      measured on the sibs of the candidates, are costly and require a high level of
      reproductive control. The most widely used alternative is a selection scheme,
      where families are reared communally and the candidates are selected based on
      their own individual measurements of the traits under selection. However, in the
      latter selection schemes, inclusion of new traits depends on the availability of
      non-invasive techniques to measure the traits on selection candidates. This is a
      severe limitation of these schemes, especially for disease resistance and fillet
      quality traits. METHODS: Here, we present a new selection scheme, which was
      validated using computer simulations comprising 100 families, among which 1, 10
      or 100 were reared communally in groups. Pooling of the DNA from 2000, 20000 or
      50000 test individuals with the highest and lowest phenotypes was used to
      estimate 500, 5000 or 10000 marker effects. One thousand or 2000 out of 20000
      candidates were preselected for a growth-like trait. These pre-selected
      candidates were genotyped, and they were selected on their genome-wide breeding
      values for a trait that could not be measured on the candidates. RESULTS: A high
      accuracy of selection, i.e. 0.60-0.88 was obtained with 20000-50000 test
      individuals but it was reduced when only 2000 test individuals were used. This
      shows the importance of having large numbers of phenotypic records to accurately
      estimate marker effects. The accuracy of selection decreased with increasing
      numbers of families per group. CONCLUSIONS: This new selection scheme combines
      communal rearing of families, pre-selection of candidates, DNA pooling and
      genomic selection and makes multi-trait selection possible in aquaculture
      selection schemes without keeping families separately until individual tagging is
      possible. The new scheme can also be used for other farmed species, for which the
      cost of genotyping test individuals may be high, e.g. if trait heritability is
      low.

PMID- 21092199
TI  - The revised Bethesda guidelines: extent of utilization in a university hospital
      medical center with a cancer genetics program.
AB  - BACKGROUND: In 1996, the National Cancer Institute hosted an international
      workshop to develop criteria to identify patients with colorectal cancer who
      should be offered microsatellite instability (MSI) testing due to an increased
      risk for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). These criteria were
      further modified in 2004 and became known as the revised Bethesda Guidelines. Our
      study aimed to retrospectively evaluate the percentage of patients diagnosed with
      HNPCC tumors in 2004 who met revised Bethesda criteria for MSI testing, who were
      referred for genetic counseling within our institution. METHODS: All HNPCC tumors
      diagnosed in 2004 were identified by accessing CoPath, an internal database. Both
      the Tumor Registry and patients' electronic medical records were accessed to
      collect all relevant family history information. The list of patients who met at
      least one of the revised Bethesda criteria, who were candidates for MSI testing,
      was then cross-referenced with the database of patients referred for genetic
      counseling within our institution. RESULTS: A total of 380 HNPCC-associated
      tumors were diagnosed at our institution during 2004 of which 41 (10.7%) met at
      least one of the revised Bethesda criteria. Eight (19.5%) of these patients were
      referred for cancer genetic counseling of which 2 (25%) were seen by a genetics
      professional. Ultimately, only 4.9% of patients eligible for MSI testing in 2004
      were seen for genetic counseling. CONCLUSION: This retrospective study identified
      a number of barriers, both internal and external, which hindered the
      identification of individuals with HNPCC, thus limiting the ability to
      appropriately manage these high risk families.

PMID- 21092200
TI  - Legionella pneumophila induces cathepsin B-dependent necrotic cell death with
      releasing high mobility group box1 in macrophages.
AB  - BACKGROUND: Legionella pneumophila (LPN) can cause a lethal infectious disease
      with a marked inflammatory response in humans. However, the mechanism of this
      severe inflammation remains poorly understood. Since necrosis is known to induce
      inflammation, we investigated whether LPN induces necrosis in macrophages. We
      also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death.
      METHODS: The human monocytic cell line THP-1 was infected with LPN, NUL1 strain.
      MG132-treated cells were used as apoptotic control cells. After infection, the
      type of cell death was analyzed by using microscopy, LDH release and flow
      cytometry. As a proinflammatory mediator, high-mobility group box 1 (HMGB-1), was
      measured. Cathepsin B activity was also measured and the inhibitory effects of
      cathepsin B on LPN-induced cell death were analyzed. RESULTS: THP-1 cells after
      treatment with high dose of LPN showed necrotic features with releasing HMGB-1.
      This necrosis and the HMGB-1 release were inhibited by a specific lysosomal
      cathepsin B inhibitor and were characterized by a rapid and high activation of
      cathepsin B that was not observed in apoptotic control cells. The necrosis was
      also accompanied by cathepsin B-dependent poly(ADP-ribose) polymerase (PARP)
      cleavage. CONCLUSIONS: We demonstrate here that L. pneumophila rapidly induces
      cathepsin B-dependent necrosis in a dose-dependent manner and releases a
      proinflammatory mediator, HMGB-1, from macrophages. This report describes a novel
      aspect of the pathogenesis of Legionnaires' disease and provides a possible
      therapeutic target for the regulation of inflammation.

PMID- 21092201
TI  - Regulators of ribonucleotide reductase inhibit Ty1 mobility in saccharomyces
      cerevisiae.
AB  - BACKGROUND: Ty1 is a long terminal repeat retrotransposon of Saccharomyces
      cerevisiae, with a replication cycle similar to retrovirus replication.
      Structurally, Ty1 contains long terminal repeat (LTR) regions flanking the gag
      and pol genes that encode for the proteins that enable Ty1 mobility. Reverse
      transcriptase produces Ty1 complementary (c)DNA that can either be integrated
      back into the genome by integrase or recombined into the yeast genome through
      homologous recombination. The frequency of Ty1 mobility is temperature sensitive,
      with optimum activity occurring at 24-26 degrees C. RESULTS: In this study, we
      identified two host genes that when deleted allow for high temperature Ty1
      mobility: RFX1 and SML1. The protein products of these genes are both negative
      regulators of the enzyme ribonucleotide reductase, a key enzyme in regulating
      deoxyribonucleotide triphosphate (dNTP) levels in the cell. Processing of Ty1
      proteins is defective at high temperature, and processing is not improved in
      either rfx1 or sml1 deletion strains. Ty1 mobility at high temperature is
      mediated by homologous recombination of Ty1 cDNA to Ty1 elements within the yeast
      genome. We quantified cDNA levels in wild type, rfx1 and sml1 deletion background
      strains at different temperatures. Southern blot analysis demonstrated that cDNA
      levels were not markedly different between the wild type and mutant strains as
      temperatures increased, indicating that the increased Ty1 mobility is not a
      result of increased cDNA synthesis in the mutant strains. Homologous
      recombination efficiency was increased in both rfx1 and sml1 deletion strains at
      high temperatures; the rfx1 deletion strain also had heightened homologous
      recombination efficiency at permissive temperatures. In the presence of the dNTP
      reducing agent hydroxyurea at permissive temperatures, Ty1 mobility was
      stimulated in the wild type and sml1 deletion strains but not in the rfx1
      deletion strain. Mobility frequency was greatly reduced in all strains at high
      temperature. Deletion of the S-phase checkpoint pathway Dun1 kinase, which
      inactivates Sml1 and Rfx1, reduced Ty1 mobility at a range of temperatures.
      CONCLUSIONS: Levels of cellular dNTPs, as regulated by components of the S-phase
      checkpoint pathway, are a limiting factor in homologous recombination-mediated
      Ty1 mobility.

PMID- 21092202
TI  - Clinical application for the preservation of phospho-proteins through in-situ
      tissue stabilization.
AB  - BACKGROUND: Protein biomarkers will play a pivotal role in the future of
      personalized medicine for both diagnosis and treatment decision-making. While the
      results of several pre-clinical and small-scale clinical studies have
      demonstrated the value of protein biomarkers, there have been significant
      challenges to translating these findings into routine clinical care. Challenges
      to the use of protein biomarkers include inter-sample variability introduced by
      differences in post-collection handling and ex vivo degradation of proteins and
      protein modifications. RESULTS: In this report, we re-create laboratory and
      clinical scenarios for sample collection and test the utility of a new tissue
      stabilization technique in preserving proteins and protein modifications. In the
      laboratory setting, tissue stabilization with the Denator Stabilizor T1 resulted
      in a significantly higher yield of phospho-protein when compared to standard snap
      freeze preservation. Furthermore, in a clinical scenario, tissue stabilization at
      collection resulted in a higher yield of total phospho-protein, total phospho
      tyrosine, pErkT202/Y204 and pAktS473 when compared to standard methods. Tissue
      stabilization did not have a significant effect on other post-translational
      modifications such as acetylation and glycosylation, which are more stable ex
      vivo. Tissue stabilization did decrease total RNA quantity and quality.
      CONCLUSION: Stabilization at the time of collection offers the potential to
      better preserve tissue protein and protein modification levels, as well as reduce
      the variability related to tissue processing delays that are often associated
      with clinical samples.

PMID- 21092203
TI  - Physiological characteristics of the extreme thermophile Caldicellulosiruptor
      saccharolyticus: an efficient hydrogen cell factory.
AB  - Global concerns about climate changes and their association with the use of
      fossil fuels have accelerated research on biological fuel production. Biological
      hydrogen production from hemicellulose-containing waste is considered one of the
      promising avenues. A major economical issue for such a process, however, is the
      low substrate conversion efficiency. Interestingly, the extreme thermophilic
      bacterium Caldicellulosiruptor saccharolyticus can produce hydrogen from
      carbohydrate-rich substrates at yields close to the theoretical maximum of the
      dark fermentation process (i.e., 4 mol H2/mol hexose). The organism is able to
      ferment an array of mono-, di- and polysaccharides, and is relatively tolerant to
      high partial hydrogen pressures, making it a promising candidate for exploitation
      in a biohydrogen process. The behaviour of this Gram-positive bacterium bears all
      hallmarks of being adapted to an environment sparse in free sugars, which is
      further reflected in its low volumetric hydrogen productivity and low
      osmotolerance. These two properties need to be improved by at least a factor of
      10 and 5, respectively, for a cost-effective industrial process. In this review,
      the physiological characteristics of C. saccharolyticus are analyzed in view of
      the requirements for an efficient hydrogen cell factory. A special emphasis is
      put on the tight regulation of hydrogen production in C. saccharolyticus by both
      redox and energy metabolism. Suggestions for strategies to overcome the current
      challenges facing the potential use of the organism in hydrogen production are
      also discussed.

PMID- 21092204
TI  - Image cytometric analysis of p53 and mdm-2 expression in primary and recurrent
      mucoepidermoid carcinoma of parotid gland: immunohistochemical study.
AB  - AIMS AND OBJECTIVES: This study aims to analyze immunocytochemically p53 aberrant
      expression and mdm-2 expression in primary and recurrent mucoepidermoid carcinoma
      (MEC) of parotid gland and to ascertain if expression of these markers correlates
      with tumor behavior, clinical outcome, histological grade and local recurrence.
      METHODS: 20 cases histologically diagnosed as primary MEC with different grades
      were included in the study. Out of 20 cases, 7 were classified as grade I, 8 as
      grade II and 5 as grade III. Immunohistochemical staining of these 20 primary
      cases as well as 6 recurrent cases with anti-p53 and anti-mdm-2 antibodies was
      carried out. Area fraction of immunopositivity was estimated by image analysis
      software. RESULTS: 16/20 primary cases were p53 +ve (80%). The p53 positive cases
      included 3 cases classified as grade (I), 8 cases as grade (II) and 5 cases as
      grade (III). All 6 recurrent cases were p53 +ve. On the other hand, 14/20 primary
      and only 2/6 recurrent cases were mdm-2 +ve. The mdm-2 +ve primary cases included
      2 classified as grade (I), 7 as grade (II) and 5 as grade (III). 12 primary MEC
      showed co-expression of both p53 and mdm-2 of which 2 cases showed local
      recurrence. CONCLUSIONS: These data suggested that expression of p53 and mdm-2 in
      primary and recurrent MEC correlates with the high histological grade. P53
      aberrant expression is not only considered as an early event in MEC
      carcinogenesis but also correlates to tumor behavior and local recurrence. Mdm-2
      overexpression is correlated to pathogenesis of MEC. However, no strong evidence
      was found between mdm-2 expression and MEC local recurrence.

PMID- 21092205
TI  - Shifting gears higher--digital slides in graduate education--4 years experience
      at Semmelweis University.
AB  - BACKGROUND: The spreading of whole slide imaging or digital slide systems in
      pathology as an innovative technique seems to be unstoppable. Successful
      introduction of digital slides in education has played a crucial role to reach
      this level of acceptance. Practically speaking there is no university institute
      where digital materials are not built into pathology education. At the 1st.
      Department of Pathology and Experimental Cancer Research, Semmelweis University
      optical microscopes have been replaced and for four years only digital slides
      have been used in education. The aim of this paper is to summarize our
      experiences gathered with the installation of a fully digitized histology lab for
      graduate education. METHODS: We have installed a digital histology lab with 40
      PCs, two slide servers - one for internal use and one with external internet
      access. We have digitized hundreds of slides and after 4 years we use a set of
      126 slides during the pathology course. A Student satisfaction questionnaire and
      a Tutor satisfaction questionnaire have been designed, both to be completed
      voluntarily to have feed back from the users. The page load statistics of the
      external slide server were evaluated. RESULTS: The digital histology lab served
      ~900 students and ~1600 hours of histology practice. The questionnaires revealed
      high satisfaction with digital slides. The results also emphasize the importance
      of the tutors' attitude towards digital microscopy as a factor influencing the
      students' satisfaction. The constantly growing number of page downloads from the
      external server confirms this satisfaction and the acceptance of digital slides.
      CONCLUSIONS: We are confident, and have showed as well, that digital slides have
      got numerous advantages over optical slides and are more suitable in education.

PMID- 21092206
TI  - Contrast-enhanced sonography as a novel tool for assessment of vascular
      malformations.
AB  - BACKGROUND: Vascular malformations with arteriovenous shunt components can cause
      significant disability, chronic pain, and functional impairment. Effective
      treatment may require serial procedures, yet an imaging modality optimized to
      control cost and reduce radiation exposure in this predominantly pediatric
      population has not yet been identified. METHODS AND RESULTS: We describe the use
      of contrast-enhanced sonography as a novel tool to define vascular anatomy and
      localize arteriovenous shunting in a young patient with a symptomatic vascular
      malformation. CONCLUSIONS: This method may effectively reduce radiation exposure
      and cost, and additionally provide unique information about arteriovenous
      shunting, offering a novel imaging application for patients with these
      conditions.

PMID- 21092207
TI  - Genetic variability and natural selection at the ligand domain of the Duffy
      binding protein in Brazilian Plasmodium vivax populations.
AB  - BACKGROUND: Plasmodium vivax malaria is a major public health challenge in Latin
      America, Asia and Oceania, with 130-435 million clinical cases per year
      worldwide. Invasion of host blood cells by P. vivax mainly depends on a type I
      membrane protein called Duffy binding protein (PvDBP). The erythrocyte-binding
      motif of PvDBP is a 170 amino-acid stretch located in its cysteine-rich region II
      (PvDBPII), which is the most variable segment of the protein. METHODS: To test
      whether diversifying natural selection has shaped the nucleotide diversity of
      PvDBPII in Brazilian populations, this region was sequenced in 122 isolates from
      six different geographic areas. A Bayesian method was applied to test for the
      action of natural selection under a population genetic model that incorporates
      recombination. The analysis was integrated with a structural model of PvDBPII,
      and T- and B-cell epitopes were localized on the 3-D structure. RESULTS: The
      results suggest that: (i) recombination plays an important role in determining
      the haplotype structure of PvDBPII, and (ii) PvDBPII appears to contain neutrally
      evolving codons as well as codons evolving under natural selection. Diversifying
      selection preferentially acts on sites identified as epitopes, particularly on
      amino acid residues 417, 419, and 424, which show strong linkage disequilibrium.
      CONCLUSIONS: This study shows that some polymorphisms of PvDBPII are present near
      the erythrocyte-binding domain and might serve to elude antibodies that inhibit
      cell invasion. Therefore, these polymorphisms should be taken into account when
      designing vaccines aimed at eliciting antibodies to inhibit erythrocyte invasion.

PMID- 21092208
TI  - Structural determinants of PINK1 topology and dual subcellular distribution.
AB  - BACKGROUND: PINK1 is a mitochondria-targeted kinase that constitutively localizes
      to both the mitochondria and the cytosol. The mechanism of how PINK1 achieves
      cytosolic localization following mitochondrial processing remains unknown.
      Understanding PINK1 subcellular localization will give us insights into PINK1
      functions and how mutations in PINK1 lead to Parkinson's disease. We asked how
      the mitochondrial localization signal, the transmembrane domain, and the kinase
      domain participate in PINK1 localization. RESULTS: We confirmed that PINK1
      mitochondrial targeting signal is responsible for mitochondrial localization.
      Once inside the mitochondria, we found that both PINK1 transmembrane and kinase
      domain are important for membrane tethering and cytosolic-facing topology. We
      also showed that PINK1 dual subcellular distribution requires both Hsp90
      interaction with the kinase domain and the proteolysis at a cleavage site
      downstream of the transmembrane domain because removal of this cleavage site
      completely abolished cytosolic PINK1. In addition, the disruption of the Hsp90
      PINK1 interaction increased mitochondrial PINK1 level. CONCLUSION: Together, we
      believe that once PINK1 enters the mitochondria, PINK1 adopts a tethered topology
      because the transmembrane domain and the kinase domain prevent PINK1 forward
      movement into the mitochondria. Subsequent proteolysis downstream of the
      transmembrane domain then releases PINK1 for retrograde movement while PINK1
      kinase domain interacts with Hsp90 chaperone. The significance of this dual
      localization could mean that PINK1 has compartmental-specific functions.

PMID- 21092209
TI  - Increased expression of sialic acid in cervical biopsies with squamous
      intraepithelial lesions.
AB  - BACKGROUND: Altered sialylation has been observed during oncogenic
      transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have
      been implicated in tumor progression and metastases. In the cervical cancer high
      levels of sialic acid have been reported in the patients serum, and an increased
      of total sialic acid concentration has been reported for the cervical neoplasia
      and cervical cancer. This study investigates the changes in expression and
      distribution of alpha2,3-linked sialic acid and alpha2,6- linked sialic acid in
      low and high squamous intraepithelial lesions and in normal tissue. METHODS:
      Lectin histochemistry was used to examine the expression and distribution of
      sialic acid in different grades of cervical neoplasia. We applied Maackia
      amurensis lectin, which interacts with alpha2,3-linked sialic acid and Sambucus
      nigra lectin specific for alpha2,6-linked sialic acid. RESULTS: The histochemical
      analysis showed that alpha2,3-linked sialic acid and alpha2,6- linked sialic acid
      increased in intensity and distribution in concordance with the grade of squamous
      intraepithelial lesion (SIL). These results are in concordance with a previous
      study that reports increased RNAm levels of three sialyltransferases.
      CONCLUSIONS: These results show that the change in sialylation occurs before
      cancer development and may play an important role in cellular transformation.
      These findings provide the basis for more detailed studies of the possible role
      of cell surface glycoconjugates bearing sialic acid in the cellular cervix
      transformation.

PMID- 21092210
TI  - Unusual case of pancreatic inflammatory myofibroblastic tumor associated with
      spontaneous splenic rupture.
AB  - BACKGROUND: Spontaneous splenic rupture considered a relatively rare but life
      threatening. The three commonest causes of spontaneous splenic rupture are
      malignant hematological diseases, viral infections and local inflammatory and
      neoplastic disorders. We describe a unique and unusual case of inflammatory
      myofibroblastic tumor of the tail of pancreas presented with massively enlarged
      spleen and spontaneous splenic rupture. CASE PRESENTATION: A 19 years old male
      patient with no significant past medical history presented to emergency room with
      abdominal pain and fatigue. Massively enlarged spleen was detected. Hypotension
      and rapid reduction of hemoglobin level necessitated urgent laparatomy. About
      1.75 liters of blood were found in abdominal cavity. A large tumor arising from
      the tail of pancreas and local rupture of an enlarged spleen adjacent to the
      tumor were detected. Distal pancreatectomy and splenectomy were performed. To our
      knowledge, we report the first case of massively enlarged spleen that was
      complicated with spontaneous splenic rupture as a result of splenic congestion
      due to mechanical obstruction caused by an inflammatory myofibroblastic tumor of
      the tail of pancreas. A review of the literature is also presented. CONCLUSION:
      Inflammatory myofibroblastic tumor of the tail of pancreas should be included in
      the differential diagnosis of the etiological causes of massively enlarged spleen
      and spontaneous splenic rupture.

PMID- 21092211
TI  - Diagnosis of carotid arterial injury in major trauma using a modification of
      Memphis criteria.
AB  - BACKGROUND: Incidence of Blunt Cerebrovascular Injuries (BCVI) after head injury
      has been reported as 0.5-1% of all admissions for blunt trauma, with a high
      stroke and mortality rate. The purpose of this study is to evaluate if a
      modification of Memphis criteria could improve the rate of BCVI diagnosis.
      METHODS: Trauma patients consecutively admitted to Intensive Care Unit (ICU) from
      Jan 2008 to Oct 2009 were considered for the study. Memphis criteria comprehend:
      basilar skull fracture with involvement of the carotid canal, cervical spine
      fracture, neurological exam not explained by brain imaging, Horner's syndrome,
      LeFort II-III fractures, and neck soft tissue injury. As single criteria
      modification, we included all patients with petrous bone fracture, even without
      carotid canal involvement. In all patients at risk of BCVI, 64-slice angio-CT
      scans was performed. RESULTS: During the study period, 266 patients were admitted
      to the ICU for blunt major trauma. Among them, 162 presented traumatic brain
      injury or cervical spine fracture. In accordance with the proposed modified
      Memphis criteria, 53 patients showed risk factors for BCVI compared to 45 using
      the original Memphis criteria. Among the 53 patients, 6 resulted as having
      carotid lesions (2.2% of all blunt major traumas; one patient more than when
      using Memphis criteria). Anticoagulant therapy with low molecular weight heparin
      was administered in all patients. No stroke or hemorrhagic complications
      occurred. Clinical examination at 6-months showed no central neurological
      deficit. CONCLUSION: A modification of a single criteria of Memphis screening
      protocol might permit the identification of a higher percentage of BCVI. Limited
      by sample size, this study needs to be validated.

PMID- 21092212
TI  - The impact of religious fasting on human health.
AB  - The past two decades have seen a rise in the number of investigations examining
      the health-related effects of religiously motivated fasts. Islamic Ramadan is a
      28 - 30 day fast in which food and drink are prohibited during the daylight
      hours. The majority of health-specific findings related to Ramadan fasting are
      mixed. The likely causes for these heterogeneous findings are the differences
      between studies in the following: 1) the amount of daily fasting time; 2) the
      percentage of subjects who smoke, take oral medications, and/or receive
      intravenous fluids; and 3) the subjects' typical food choices and eating habits.
      Greek Orthodox Christians fast for a total of 180 - 200 days each year, and their
      main fasting periods are the Nativity Fast (40 days prior to Christmas), Lent (48
      days prior to Easter), and the Assumption (15 days in August). The fasting
      periods are more similar than dissimilar, and they can each be described as a
      variant of vegetarianism. Some of the more favorable effects of these fasts
      include the lowering of body mass, total cholesterol, LDL-C, and the LDL-C/HDL-C
      ratio. The Biblical-based Daniel Fast prohibits the consumption of animal
      products, refined carbohydrates, food additives, preservatives, sweeteners,
      flavorings, caffeine, and alcohol. It is most commonly partaken for 21 days,
      although fasts of 10 and 40 days have been observed. Our initial investigation of
      the Daniel Fast noted favorable effects on several health-related outcomes,
      including: blood pressure, blood lipids, insulin sensitivity, and biomarkers of
      oxidative stress. This review summarizes the health-specific effects of these
      fasts and provides suggestions for future research.

PMID- 21092213
TI  - Development of a self-administered questionnaire to screen patients for cervical
      myelopathy.
AB  - BACKGROUND: In primary care, it is often difficult to diagnose cervical
      myelopathy. However, a delay in treatment could cause irreversible aftereffects.
      With a brief and effective self-administered questionnaire for cervical
      myelopathy, cervical myelopathy may be screened more easily and oversight may be
      avoided. As there is presently no screening tool for cervical myelopathy, the aim
      of this study was to develop a self-administered questionnaire for the screening
      of cervical myelopathy. METHODS: A case-control study was performed with the
      following two groups at our university hospital from February 2006 to September
      2008. Sixty-two patients (48 men, 14 women) with cervical myelopathy who
      underwent operative treatment were included in the myelopathy group. In the
      control group, 49 patients (20 men, 29 women) with symptoms that could be
      distinguished from those of cervical myelopathy, such as numbness, pain in the
      upper extremities, and manual clumsiness, were included. The underlying
      conditions were diagnosed as carpal tunnel syndrome, cubital tunnel syndrome,
      thoracic outlet syndrome, tarsal tunnel syndrome, diabetes mellitus neuropathy,
      cervical radiculopathy, and neuralgic amyotrophy. Twenty items for a
      questionnaire in this study were chosen from the Japanese Orthopaedic Association
      Cervical Myelopathy Evaluation Questionnaire, which is a new self-administered
      questionnaire, as an outcome measure for patients with cervical myelopathy. Data
      were analyzed by univariate analysis using the chi-square test and by multiple
      logistic regression analysis. According to the resulting odds ratio, beta
      coefficients, and p value, items were chosen and assigned a score. RESULTS: Eight
      items were chosen by univariate and multiple logistic regression analyses and
      assigned a score. The Hosmer-Lemeshow statistic showed p = 0.805. The area under
      the receiver operation characteristic curve was 0.86. The developed questionnaire
      had a sensitivity of 93.5% and a specificity of 67.3%. CONCLUSIONS: We
      successfully developed a simple self-administered questionnaire to screen for
      cervical myelopathy.

PMID- 21092214
TI  - Fungal-associated NO is involved in the regulation of oxidative stress during
      rehydration in lichen symbiosis.
AB  - BACKGROUND: Reactive oxygen species (ROS) are normally produced in respiratory
      and photosynthetic electron chains and their production is enhanced during
      desiccation/rehydration. Nitric oxide (NO) is a ubiquitous and multifaceted
      molecule involved in cell signaling and abiotic stress. Lichens are
      poikilohydrous organisms that can survive continuous cycles of desiccation and
      rehydration. Although the production of ROS and NO was recently demonstrated
      during lichen rehydration, the functions of these compounds are unknown. The aim
      of this study was to analyze the role of NO during rehydration of the lichen
      Ramalina farinacea (L.) Ach., its isolated photobiont partner Trebouxia sp. and
      Asterochloris erici (Ahmadjian) Skaloud et Peksa (SAG 32.85 = UTEX 911). RESULTS:
      Rehydration of R. farinacea caused the release of ROS and NO evidenced by the
      fluorescent probes DCFH2-DA and DAN respectively. However, a minimum in lipid
      peroxidation (MDA) was observed 2 h post-rehydration. The inhibition of NO in
      lichen thalli with c-PTIO resulted in increases in both ROS production and lipid
      peroxidation, which now peaked at 3 h, together with decreases in chlorophyll
      autofluorescence and algal photobleaching upon confocal laser incidence.
      Trebouxia sp. photobionts generate peaks of NO-endproducts in suspension and show
      high rates of photobleaching and ROS production under NO inhibition which also
      caused a significant decrease in photosynthetic activity of A. erici axenic
      cultures, probably due to the higher levels of photo-oxidative stress.
      CONCLUSIONS: Mycobiont derived NO has an important role in the regulation of
      oxidative stress and in the photo-oxidative protection of photobionts in lichen
      thalli. The results point to the importance of NO in the early stages of lichen
      rehydration.

PMID- 21092216
TI  - Leiomyosarcoma of intravascular origin--a rare tumor entity: clinical
      pathological study of twelve cases.
AB  - BACKGROUND: Leiomysarcoma of intravascular origin is an exceedingly rare entity
      of malignant soft tissue tumors. They are most frequently encountered in the
      retroperitoneum arising from the inferior vena cava and are scarcely found to
      arise from vessels of the extremities. These tumors were analysed with particular
      reference to treatment outcome and prognosis. The aim of this article is to
      broaden the knowledge of the clinical course of this rare malignancy. METHOD:
      During 2000 and 2009 twelve patients were identified with an intravascular origin
      of a leiomyosarcoma. Details regarding the clinical course, follow-up and outcome
      were assessed with focus on patient survival, tumor relapse and metastases and
      treatment outcome. 3 year survival probability was calculated using Kaplan-Meier
      method. RESULTS: Vascular leiomyosarcomas accounted for 0.7% of all malignant
      soft tissue tumors treated at our soft tissue sarcoma reference center. The mean
      follow up period was 38 months. Tumor relapse was encountered in six patients. 6
      patients developed metastatic disease. The three year survival was 57%.
      CONCLUSION: Vascular leiomysarcoma is a rare but aggressive tumor entity with a
      high rate of local recurrence and metastasis.

PMID- 21092215
TI  - Metabolic response of Geobacter sulfurreducens towards electron donor/acceptor
      variation.
AB  - BACKGROUND: Geobacter sulfurreducens is capable of coupling the complete
      oxidation of organic compounds to iron reduction. The metabolic response of G.
      sulfurreducens towards variations in electron donors (acetate, hydrogen) and
      acceptors (Fe(III), fumarate) was investigated via (13)C-based metabolic flux
      analysis. We examined the (13)C-labeling patterns of proteinogenic amino acids
      obtained from G. sulfurreducens cultured with (13)C-acetate. RESULTS: Using (13)C
      based metabolic flux analysis, we observed that donor and acceptor variations
      gave rise to differences in gluconeogenetic initiation, tricarboxylic acid cycle
      activity, and amino acid biosynthesis pathways. Culturing G. sulfurreducens cells
      with Fe(III) as the electron acceptor and acetate as the electron donor resulted
      in pyruvate as the primary carbon source for gluconeogenesis. When fumarate was
      provided as the electron acceptor and acetate as the electron donor, the flux
      analysis suggested that fumarate served as both an electron acceptor and, in
      conjunction with acetate, a carbon source. Growth on fumarate and acetate
      resulted in the initiation of gluconeogenesis by phosphoenolpyruvate
      carboxykinase and a slightly elevated flux through the oxidative tricarboxylic
      acid cycle as compared to growth with Fe(III) as the electron acceptor. In
      addition, the direction of net flux between acetyl-CoA and pyruvate was reversed
      during growth on fumarate relative to Fe(III), while growth in the presence of
      Fe(III) and acetate which provided hydrogen as an electron donor, resulted in
      decreased flux through the tricarboxylic acid cycle. CONCLUSIONS: We gained
      detailed insight into the metabolism of G. sulfurreducens cells under various
      electron donor/acceptor conditions using (13)C-based metabolic flux analysis. Our
      results can be used for the development of G. sulfurreducens as a chassis for a
      variety of applications including bioremediation and renewable biofuel
      production.

PMID- 21092217
TI  - Review for the generalist: evaluation of low back pain in children and
      adolescents.
AB  - Back pain is common in children and adolescents. Most cases of back pain are non
      specific and self-limiting. In children and adolescents, pain is usually related
      to the posterior elements of the spine and disc-related problems are rare.
      Serious pathology, including malignancy and infection needs to be excluded.
      Evaluation and management is challenging and requires a thorough history and
      physical exam, and understanding of the immature skeleton. Diagnostic imaging is
      useful in the evaluation of a child or adolescent with low back pain and can help
      guide management. This article will review common causes of back pain in the
      pediatric population.

PMID- 21092218
TI  - Multimorbidity - not just an older person's issue. Results from an Australian
      biomedical study.
AB  - BACKGROUND: Multimorbidity, the simultaneous occurrence of two or more chronic
      conditions, is usually associated with older persons. This research assessed
      multimorbidity across a range of ages so that planners are informed and
      appropriate prevention programs, management strategies and health service/health
      care planning can be implemented. METHODS: Multimorbidity was assessed across
      three age groups from data collected in a major biomedical cohort study (North
      West Adelaide Health Study). Using randomly selected adults, diabetes, asthma,
      and chronic obstructive pulmonary disease were determined clinically and cardio
      vascular disease, osteoporosis, arthritis and mental health by self-report (ever
      been told by a doctor). A range of demographic, social, risk and protective
      factors including high blood pressure and high cholesterol (assessed bio
      medically), health service use, quality of life and medication use (linked to
      government records) were included in the multivariate modelling. RESULTS: Overall
      4.4% of the 20-39 year age group, 15.0% of the 40-59 age group and 39.2% of those
      aged 60 years of age or older had multimorbidity (17.1% of the total). Of those
      with multimorbidity, 42.1% were aged less than 60 years of age. A variety of
      variables were included in the final logistic regression models for the three age
      groups including family structure, marital status, education attainment, country
      of birth, smoking status, obesity measurements, medication use, health service
      utilisation and overall health status. CONCLUSIONS: Multimorbidity is not just
      associated with older persons and flexible care management support systems,
      appropriate guidelines and care-coordination programs are required across a
      broader age range. Issues such as health literacy and polypharamacy are also
      important considerations. Future research is required into assessing
      multimorbidity across the life course, prevention of complications and assessment
      of appropriate self-care strategies.

PMID- 21092219
TI  - A biologically competitive 21 days hypofractionation scheme with weekly
      concomitant boost in breast cancer radiotherapy feasibility acute sub-acute and
      short term late effects.
AB  - BACKGROUND: Radiation therapy after lumpectomy is a standard part of breast
      conserving therapy for invasive breast carcinoma. The most frequently used
      schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that
      sporadically may dissuade some otherwise eligible women from undertaking
      treatment. The purpose and primary endpoint of this perspective study is to
      evaluate feasibility and short-term late toxicity in a hypofractionated whole
      breast irradiation schedule. METHODS: Between February and October 2008 we
      treated 65 consecutive patients with operable invasive early-stage breast cancer
      with a hypofractionated schedule of external beam radiation therapy. All patients
      were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a
      concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions.
      RESULTS: All the patients had achieved a median follow up of 24 months (range 21
      29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had
      grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were
      34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3%
      of patients presented with clinical grade 1 and grade 2 fibrosis respectively and
      5% presented grade 1 hyperpigmentation. The remaining patients were free of side
      effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of
      late fibrosis. CONCLUSIONS: The clinical results observed showed a reasonably
      good feasibility of the accelerated hypofractionated schedule in terms of acute,
      subacute and short-term late toxicity. This useful 13 fractions with a
      concomitant boost schedule seems, in selected patients, a biologically acceptable
      alternative to the traditional 30 days regime.

PMID- 21092220
TI  - Early variations in plasmodium falciparum dynamics in Nigerian children after
      treatment with two artemisinin-based combinations: implications on delayed
      parasite clearance.
AB  - BACKGROUND: Combination treatments, preferably containing an artemisinin
      derivative, are recommended to improve efficacy and prevent Plasmodium falciparum
      drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are
      efficacious regimens that have been widely adopted in sub-Saharan Africa.
      However, most study designs ignore the effects of these regimens on peripheral
      parasitaemia in the first 24 hours of therapy. The study protocol was designed to
      evaluate more closely the early effects and the standard measures of efficacies
      of these two regimens. METHODS: In an open label, randomized controlled clinical
      trial, children aged 12 months to 132 months were randomized to receive AL (5-14
      kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or
      artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days.
      Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h,
      and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic
      identification and quantification of Plasmodium falciparum. RESULTS: A total of
      193 children were randomized to receive either AL (97) or AA (96). In children
      that received both medications, early response of peripheral parasitaemia showed
      that 42% of children who received AL and 36.7% of those who received AA had an
      immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a
      rapid fall. The rise in parasitaemia was significant and seems to suggest a
      mobilization of asexual parasites from the deep tissues to the periphery. Days 3,
      7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in
      both groups of children. Both drug combinations were well tolerated with minimal
      side effects. CONCLUSION: The study showed the high efficacy of AL and AA in
      Nigerian children. In addition the study demonstrated the mobilisation of asexual
      parasites from the deep to the periphery in the early hours of commencing ACT
      treatment in a subset of patients in both study groups. It is unclear whether the
      early parasite dynamics discovered in this study play any role in the development
      of drug resistance and thus it is important to further evaluate this discovery.
      It may be useful for studies investigating delay in parasite clearance of
      artemisinin derivatives as a way of monitoring the development of resistance to
      artemisinin to assess the early effects of the drugs on the parasites.

PMID- 21092221
TI  - Effect of adding the novel fiber, PGX(r), to commonly consumed foods on glycemic
      response, glycemic index and GRIP: a simple and effective strategy for reducing
      post prandial blood glucose levels--a randomized, controlled trial.
AB  - BACKGROUND: Reductions in postprandial glycemia have been demonstrated previously
      with the addition of the novel viscous polysaccharide (NVP), PolyGlycopleX(r)
      (PGX(r)), to an OGTT or white bread. This study explores whether these reductions
      are sustained when NVP is added to a range of commonly consumed foods or
      incorporated into a breakfast cereal. METHODS: Ten healthy subjects (4M, 6F; age
      37.3 +/- 3.6 y; BMI 23.8 +/- 1.3 kg/m2), participated in an acute, randomized
      controlled trial. The glycemic response to cornflakes, rice, yogurt, and a frozen
      dinner with and without 5 g of NVP sprinkled onto the food was determined. In
      addition, 3 granolas with different levels of NVP and 3 control white breads and
      one white bread and milk were also consumed. All meals contained 50 g of
      available carbohydrate. Capillary blood samples were taken fasting and at 15, 30,
      45, 60, 90 and 120 min after the start of the meal. The glycemic index (GI) and
      the glycemic reduction index potential (GRIP) were calculated. The blood glucose
      concentrations at each time and the iAUC values were subjected to repeated
      measures analysis of variance (ANOVA) examining for the effect of test meal.
      After demonstration of significant heterogeneity, differences between individual
      means was assessed using GLM ANOVA with Tukey test to adjust for multiple
      comparisons. RESULTS: Addition of NVP reduced blood glucose response irrespective
      of food or dose (p < 0.01). The GI of cornflakes, cornflakes+NVP, rice, rice+NVP,
      yogurt, yogurt+NVP, turkey dinner, and turkey dinner+NVP were 83 +/- 8, 58 +/- 7,
      82 +/- 8, 45 +/- 4, 44 +/- 4, 38 +/- 3, 55 +/- 5 and 41 +/- 4, respectively. The
      GI of the control granola, and granolas with 2.5 and 5 g of NVP were 64 +/- 6, 33
      +/- 5, and 22 +/- 3 respectively. GRIP was 6.8 +/- 0.9 units per/g of NVP.
      CONCLUSION: Sprinkling or incorporation of NVP into a variety of different foods
      is highly effective in reducing postprandial glycemia and lowering the GI of a
      food. CLINICAL TRIAL REGISTRATION: NCT00935350.

PMID- 21092222
TI  - LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer.
AB  - BACKGROUND: Most colorectal carcinomas are driven by an activation of the
      canonical Wnt signalling pathway, which promotes the expression of multiple
      target genes mediating proliferation inavasion and invasion. Upon activation of
      the Wnt signalling pathway its key player beta-catenin translocates from the
      cytoplasm to the nucleus and binds to members of the T-cell factor (TCF)/lymphoid
      enhancer factor (LEF-1) family namely LEF-1 and TCF4 which are central mediators
      of transcription. In this study we investigated the expression of beta-Catenin,
      LEF1 and TCF4 in colorectal carcinomas and their prognostic significance.
      METHODS: Immunohistochemical analyses of LEF-1, TCF4 and nuclear beta-Catenin
      were done using a tissue microarray with 214 colorectal cancer specimens. The
      expression patterns were compared with each other and the results were correlated
      with clinicopathologic variables and overall survival in univariate and
      multivariate analysis. RESULTS: LEF-1 expression was found in 56 (26%) and TCF4
      expression in 99 (46%) of colorectal carcinomas and both were heterogeneously
      distributed throughout the tumours. Comparing LEF-1, TCF4 and beta-catenin
      expression patterns we found no correlation. In univariate analysis, TCF4
      expression turned out to be a negative prognostic factor being associated with
      shorter overall survival (p = 0.020), whereas LEF-1 expression as well as a LEF
      1/TCF4 ratio were positive prognostic factors and correlated with longer overall
      survival (p = 0.015 respectively p = 0.001). In multivariate analysis, LEF-1 and
      TCF4 expression were confirmed to be independent predictors of longer
      respectively shorter overall survival, when considered together with tumour
      stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4:
      2.18; p = 0.014). CONCLUSIONS: This study demonstrates different prognostic
      values of LEF-1 and TCF4 expression in colorectal cancer patients indicating
      different regulation of these transcription mediators during tumour progression.
      Moreover both factors may serve as new potential predictive markers in low stage
      colon cancer cases in advance.

PMID- 21092223
TI  - Associations of quality of life with physical activity, fruit and vegetable
      consumption, and physical inactivity in a free living, multiethnic population in
      Hawaii: a longitudinal study.
AB  - INTRODUCTION: High intake of fruit and vegetables and being physically active are
      associated with reduced risk of chronic diseases. In the current study, we
      examined the associations of physical activity, fruit and vegetable consumption,
      and TV/video watching (indicator for physical inactivity) with perceived quality
      of life (QOL) in a sample of free living adults. METHODS: A cohort (N = 139) from
      a random, multi-ethnic sample of 700 adults living in Hawaii was evaluated at 3
      month intervals for the first year and 6-month intervals for the second year. QOL
      was assessed from self-reports of mental or physical health at the end of the
      study. RESULTS: Overall, the cohort participants appeared to maintain relatively
      constant levels of physical activity, fruit and vegetable intake, and TV/video
      watching. Physical activity was positively related to mental health (p-values <
      0.05), but not physical health, at all time points regardless of participants'
      fruit and vegetable consumption and hours of TV/video watching. Neither mental
      nor physical health was associated with fruit and vegetable intake or TV/video
      watching. CONCLUSION: Our study supports that physical activity is positively
      associated with mental health. Fruit and vegetable consumption and TV/video
      watching may be too specific to represent an individual's overall nutritional
      status and physical inactivity, respectively.

PMID- 21092224
TI  - Hypoglycaemia in severe malaria, clinical associations and relationship to
      quinine dosage.
AB  - BACKGROUND: Hypoglycaemia is an independent risk factor for death in severe
      malaria and a recognized adverse treatment effect of parenteral quinine. In 2006
      our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10
      mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new
      WHO guidelines. This presented us with the opportunity to examine whether there
      was any dose relationship of quinine and hypoglycaemia occurrence. METHODS:
      Retrospective case notes review of all children admitted to hospital with severe
      falciparum malaria between April 2002 - July 2009, before and after the
      introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels
      were measured until intravenous quinine was discontinued. Clinical events
      immediately preceding or concurrent with each episode of hypoglycaemia (glucose <
      = 3.0 mmol/l) were recorded. RESULTS: 954 children received the old quinine
      regime and 283 received the new regime. We found no evidence of an increased
      prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former
      (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2
      mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity
      markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but
      less commonly with seizures (10%). Disruption of maintenance fluids and/or blood
      transfusion concurred with 42% of the hypoglycaemia episodes. Post admission
      hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic
      counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P <
      0.01. CONCLUSION: There was no evidence to indicate a dose relationship between
      quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity
      features, disruption of glucose infusion and transfusion. Careful glucose
      monitoring should be targeted to these complications where resources are limited.

PMID- 21092225
TI  - Assessment of surfactant protein A (SP-A) dependent agglutination.
AB  - BACKGROUND: Monomers of the collectin surfactant associated protein-A (SP-A) are
      arranged in trimers and higher oligomers. The state of oligomerization differs
      between individuals and likely affects SP-A's functional properties. SP-A can
      form aggregates together with other SP-A molecules. Here we report and assess a
      test system for the aggregate forming properties of SP-A in serum and broncho
      alveolar lavage samples. METHODS: Anti-SP-A antibodies fixed to latex beads bound
      SP-A at its N-terminal end and allowed the interaction with other SP-A molecules
      in a given sample by their C-terminal carbohydrate recognition domain (CRD) to
      agglutinate the beads to aggregates, which were quantified by light microscopy.
      RESULTS: SP-A aggregation was dependent on its concentration, the presence of
      calcium, and was dose-dependently inhibited by mannose. Unaffected by the
      presence of SP-D no aggregation was observed in absence of SP-A. The more complex
      the oligomeric structure of SP-A present in a particular sample, the better was
      its capability to induce aggregation at a given total concentration of SP-A. SP-A
      in serum agglutinated independently of the pulmonary disease; in contrast SP-A in
      lung lavage fluid was clearly inferior in patients with chronic bronchitis and
      particularly with cystic fibrosis compared to controls. CONCLUSIONS: The
      functional status of SP-A with respect to its aggregating properties in serum and
      lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with
      severe neutrophilic bronchitis was inferior.

PMID- 21092226
TI  - Knowledge-based biomedical word sense disambiguation: comparison of approaches.
AB  - BACKGROUND: Word sense disambiguation (WSD) algorithms attempt to select the
      proper sense of ambiguous terms in text. Resources like the UMLS provide a
      reference thesaurus to be used to annotate the biomedical literature. Statistical
      learning approaches have produced good results, but the size of the UMLS makes
      the production of training data infeasible to cover all the domain. METHODS: We
      present research on existing WSD approaches based on knowledge bases, which
      complement the studies performed on statistical learning. We compare four
      approaches which rely on the UMLS Metathesaurus as the source of knowledge. The
      first approach compares the overlap of the context of the ambiguous word to the
      candidate senses based on a representation built out of the definitions, synonyms
      and related terms. The second approach collects training data for each of the
      candidate senses to perform WSD based on queries built using monosemous synonyms
      and related terms. These queries are used to retrieve MEDLINE citations. Then, a
      machine learning approach is trained on this corpus. The third approach is a
      graph-based method which exploits the structure of the Metathesaurus network of
      relations to perform unsupervised WSD. This approach ranks nodes in the graph
      according to their relative structural importance. The last approach uses the
      semantic types assigned to the concepts in the Metathesaurus to perform WSD. The
      context of the ambiguous word and semantic types of the candidate concepts are
      mapped to Journal Descriptors. These mappings are compared to decide among the
      candidate concepts. Results are provided estimating accuracy of the different
      methods on the WSD test collection available from the NLM. CONCLUSIONS: We have
      found that the last approach achieves better results compared to the other
      methods. The graph-based approach, using the structure of the Metathesaurus
      network to estimate the relevance of the Metathesaurus concepts, does not perform
      well compared to the first two methods. In addition, the combination of methods
      improves the performance over the individual approaches. On the other hand, the
      performance is still below statistical learning trained on manually produced data
      and below the maximum frequency sense baseline. Finally, we propose several
      directions to improve the existing methods and to improve the Metathesaurus to be
      more effective in WSD.

PMID- 21092227
TI  - Clinical outcomes and safety assessment in elderly patients undergoing
      decompressive laminectomy for lumbar spinal stenosis: a prospective study.
AB  - BACKGROUND: To assess safety, risk factors and clinical outcomes in elderly
      patients with spinal stenosis after decompressive laminectomy. METHODS: A
      prospective cohort of patients 70 years and older with spinal stenosis undergoing
      conventional laminectomy without fusion (n = 101) were consecutively enrolled
      from regular clinical practice and reassessed at 3 and 12 months. Primary outcome
      was change in health related quality of life measured (HRQL) with EuroQol-5 D (EQ
      5D). Secondary outcomes were safety assessment, changes in Oswestry disability
      index (ODI), Visual Analogue Scale (EQ-VAS) score for self reported health, VAS
      score for leg and back pain and patient satisfaction. We used regression analyses
      to evaluate risk factors for less improvement. RESULTS: The mean EQ-5 D total
      score were 0.32, 0.63 and 0.60 at baseline, 3 months and 12 months respectively,
      and represents a statistically significant (P < 0.001) improvement. Effect size
      was > 0.8. Mean ODI score at baseline was 44.2, at 3 months 25.6 and at 27.9.
      This represents an improvement for all post-operative scores. A total of 18
      (18.0%) complications were registered with 6 (6.0%) classified as major,
      including one perioperative death. Patients stating that the surgery had been
      beneficial at 3 months was 82 (89.1%) and at 12 months 73 (86.9%). The only
      predictor found was patients with longer duration of leg pain had less
      improvement in ODI (P < 0.001). Increased age or having complications did not
      predict a worse outcome in any of the outcome variables. CONCLUSIONS: Properly
      selected patients of 70 years and older can expect a clinical meaningful
      improvement of HRQL, functional status and pain after open laminectomy without
      fusion. The treatment seems to be safe. However, patients with longstanding leg
      pain prior to operation are less likely to improve one year after surgery.

PMID- 21092228
TI  - Changes in weight loss, body composition and cardiovascular disease risk after
      altering macronutrient distributions during a regular exercise program in obese
      women.
AB  - BACKGROUND: This study's purpose investigated the impact of different
      macronutrient distributions and varying caloric intakes along with regular
      exercise for metabolic and physiological changes related to weight loss. METHODS:
      One hundred forty-one sedentary, obese women (38.7 +/- 8.0 yrs, 163.3 +/- 6.9 cm,
      93.2 +/- 16.5 kg, 35.0 +/- 6.2 kg*m(-2), 44.8 +/- 4.2% fat) were randomized to
      either no diet + no exercise control group (CON) a no diet + exercise control
      (ND), or one of four diet + exercise groups (high-energy diet [HED], very low
      carbohydrate, high protein diet [VLCHP], low carbohydrate, moderate protein diet
      [LCMP] and high carbohydrate, low protein [HCLP]) in addition to beginning a
      3x*week(-1) supervised resistance training program. After 0, 1, 10 and 14 weeks,
      all participants completed testing sessions which included anthropometric, body
      composition, energy expenditure, fasting blood samples, aerobic and muscular
      fitness assessments. Data were analyzed using repeated measures ANOVA with an
      alpha of 0.05 with LSD post-hoc analysis when appropriate. RESULTS: All dieting
      groups exhibited adequate compliance to their prescribed diet regimen as energy
      and macronutrient amounts and distributions were close to prescribed amounts.
      Those groups that followed a diet and exercise program reported significantly
      greater anthropometric (waist circumference and body mass) and body composition
      via DXA (fat mass and % fat) changes. Caloric restriction initially reduced
      energy expenditure, but successfully returned to baseline values after 10 weeks
      of dieting and exercising. Significant fitness improvements (aerobic capacity and
      maximal strength) occurred in all exercising groups. No significant changes
      occurred in lipid panel constituents, but serum insulin and HOMA-IR values
      decreased in the VLCHP group. Significant reductions in serum leptin occurred in
      all caloric restriction + exercise groups after 14 weeks, which were unchanged in
      other non-diet/non-exercise groups. CONCLUSIONS: Overall and over the entire test
      period, all diet groups which restricted their caloric intake and exercised
      experienced similar responses to each other. Regular exercise and modest caloric
      restriction successfully promoted anthropometric and body composition
      improvements along with various markers of muscular fitness. Significant
      increases in relative energy expenditure and reductions in circulating leptin
      were found in response to all exercise and diet groups. Macronutrient
      distribution may impact circulating levels of insulin and overall ability to
      improve strength levels in obese women who follow regular exercise.

PMID- 21092229
TI  - The Hawaiian Rhodophyta Biodiversity Survey (2006-2010): a summary of principal
      findings.
AB  - BACKGROUND: The Hawaiian red algal flora is diverse, isolated, and well studied
      from a morphological and anatomical perspective, making it an excellent candidate
      for assessment using a combination of traditional taxonomic and molecular
      approaches. Acquiring and making these biodiversity data freely available in a
      timely manner ensures that other researchers can incorporate these baseline
      findings into phylogeographic studies of Hawaiian red algae or red algae found in
      other locations. RESULTS: A total of 1,946 accessions are represented in the
      collections from 305 different geographical locations in the Hawaiian
      archipelago. These accessions represent 24 orders, 49 families, 152 genera and
      252 species/subspecific taxa of red algae. One order of red algae (the
      Rhodachlyales) was recognized in Hawaii for the first time and 196 new island
      distributional records were determined from the survey collections. One family
      and four genera are reported for the first time from Hawaii, and multiple species
      descriptions are in progress for newly discovered taxa. A total of 2,418
      sequences were generated for Hawaiian red algae in the course of this study--915
      for the nuclear LSU marker, 864 for the plastidial UPA marker, and 639 for the
      mitochondrial COI marker. These baseline molecular data are presented as neighbor
      joining trees to illustrate degrees of divergence within and among taxa. The LSU
      marker was typically most conserved, followed by UPA and COI. Phylogenetic
      analysis of a set of concatenated LSU, UPA and COI sequences recovered a tree
      that broadly resembled the current understanding of florideophyte red algal
      relationships, but bootstrap support was largely absent above the ordinal level.
      Phylogeographic trends are reported here for some common taxa within the Hawaiian
      Islands and include examples of those with, as well as without, intraspecific
      variation. CONCLUSIONS: The UPA and COI markers were determined to be the most
      useful of the three and are recommended for inclusion in future algal
      biodiversity surveys. Molecular data for the survey provide the most extensive
      assessment of Hawaiian red algal diversity and, in combination with the
      morphological/anatomical and distributional data collected as part of the
      project, provide a solid baseline data set for future studies of the flora. The
      data are freely available via the Hawaiian Algal Database (HADB), which was
      designed and constructed to accommodate the results of the project. We present
      the first DNA sequence reference collection for a tropical Pacific seaweed flora,
      whose value extends beyond Hawaii since many Hawaiian taxa are shared with other
      tropical areas.

PMID- 21092230
TI  - Luciferase expression and bioluminescence does not affect tumor cell growth in
      vitro or in vivo.
AB  - Live animal imaging is becoming an increasingly common technique for accurate and
      quantitative assessment of tumor burden over time. Bioluminescence imaging
      systems rely on a bioluminescent signal from tumor cells, typically generated
      from expression of the firefly luciferase gene. However, previous reports have
      suggested that either a high level of luciferase or the resultant light reaction
      produced upon addition of D-luciferin substrate can have a negative influence on
      tumor cell growth. To address this issue, we designed an expression vector that
      allows simultaneous fluorescence and luminescence imaging. Using fluorescence
      activated cell sorting (FACS), we generated clonal cell populations from a human
      breast cancer (MCF-7) and a mouse melanoma (B16-F10) cell line that stably
      expressed different levels of luciferase. We then compared the growth
      capabilities of these clones in vitro by MTT proliferation assay and in vivo by
      bioluminescence imaging of tumor growth in live mice. Surprisingly, we found that
      neither the amount of luciferase nor biophotonic activity was sufficient to
      inhibit tumor cell growth, in vitro or in vivo. These results suggest that
      luciferase toxicity is not a necessary consideration when designing
      bioluminescence experiments, and therefore our approach can be used to rapidly
      generate high levels of luciferase expression for sensitive imaging experiments.

PMID- 21092231
TI  - Multilocus haplotypes reveal variable levels of diversity and population
      structure of Plasmodium falciparum in Papua New Guinea, a region of intense
      perennial transmission.
AB  - BACKGROUND: The South West Pacific nation of Papua New Guinea has intense year
      round transmission of Plasmodium falciparum on the coast and in the low-lying
      inland areas. Local heterogeneity in the epidemiology of malaria suggests that
      parasites from multiple locations will need to be surveyed to define the
      population biology of P. falciparum in the region. This study describes the
      population genetics of P. falciparum in thirteen villages spread over four
      distinct catchment areas of Papua New Guinea. METHODS: Ten microsatellite loci
      were genotyped in 318 P. falciparum isolates from the parasite populations of two
      inland catchment areas, namely Wosera (number of villages (n) = 7) and Utu (n =
      1) and; and two coastal catchments, Malala (n = 3) and Mugil (n = 3). Analysis of
      the resultant multilocus haplotypes was done at different spatial scales (2-336
      km) to define the genetic diversity (allelic richness and expected
      heterozygosity), linkage disequilibrium and population structure throughout the
      study area. RESULTS: Although genetic diversity was high in all parasite
      populations, it was also variable with a lower allelic richness and expected
      heterozygosity for inland populations compared to those from the more accessible
      coast. This variability was not correlated with two proxy measures of
      transmission intensity, the infection prevalence and the proportion multiple
      infections. Random associations among the microsatellite loci were observed in
      all four catchments showing that a substantial degree of out-crossing occurs in
      the region. Moderate to very high levels of population structure were found but
      the amount of genetic differentiation (FST) did not correlate with geographic
      distance suggesting that parasite populations are fragmented. Population
      structure was also identified between villages within the Malala area, with the
      haplotypes of one parasite population clustering with the neighbouring catchment
      of Mugil. CONCLUSION: The observed population genetics of P. falciparum in this
      region is likely to be a consequence of the high transmission intensity combined
      with the isolation of human and vector populations, especially those located
      inland and migration of parasites via human movement into coastal populations.
      The variable genetic diversity and population structure of P. falciparum has
      important implications for malaria control strategies and warrants further fine
      scale sampling throughout Papua New Guinea.

PMID- 21092232
TI  - Bioinformatic analysis of ESTs collected by Sanger and pyrosequencing methods for
      a keystone forest tree species: oak.
AB  - BACKGROUND: The Fagaceae family comprises about 1,000 woody species worldwide.
      About half belong to the Quercus family. These oaks are often a source of raw
      material for biomass wood and fiber. Pedunculate and sessile oaks, are among the
      most important deciduous forest tree species in Europe. Despite their ecological
      and economical importance, very few genomic resources have yet been generated for
      these species. Here, we describe the development of an EST catalogue that will
      support ecosystem genomics studies, where geneticists, ecophysiologists,
      molecular biologists and ecologists join their efforts for understanding,
      monitoring and predicting functional genetic diversity. RESULTS: We generated
      145,827 sequence reads from 20 cDNA libraries using the Sanger method.
      Unexploitable chromatograms and quality checking lead us to eliminate 19,941
      sequences. Finally a total of 125,925 ESTs were retained from 111,361 cDNA
      clones. Pyrosequencing was also conducted for 14 libraries, generating 1,948,579
      reads, from which 370,566 sequences (19.0%) were eliminated, resulting in
      1,578,192 sequences. Following clustering and assembly using TGICL pipeline,
      1,704,117 EST sequences collapsed into 69,154 tentative contigs and 153,517
      singletons, providing 222,671 non-redundant sequences (including alternative
      transcripts). We also assembled the sequences using MIRA and PartiGene software
      and compared the three unigene sets. Gene ontology annotation was then assigned
      to 29,303 unigene elements. Blast search against the SWISS-PROT database revealed
      putative homologs for 32,810 (14.7%) unigene elements, but more extensive search
      with Pfam, Refseq_protein, Refseq_RNA and eight gene indices revealed homology
      for 67.4% of them. The EST catalogue was examined for putative homologs of
      candidate genes involved in bud phenology, cuticle formation, phenylpropanoids
      biosynthesis and cell wall formation. Our results suggest a good coverage of
      genes involved in these traits. Comparative orthologous sequences (COS) with
      other plant gene models were identified and allow to unravel the oak paleo
      history. Simple sequence repeats (SSRs) and single nucleotide polymorphisms
      (SNPs) were searched, resulting in 52,834 SSRs and 36,411 SNPs. All of these are
      available through the Oak Contig Browser http://genotoul
      contigbrowser.toulouse.inra.fr:9092/Quercus_robur/index.html. CONCLUSIONS: This
      genomic resource provides a unique tool to discover genes of interest, study the
      oak transcriptome, and develop new markers to investigate functional diversity in
      natural populations.

PMID- 21092233
TI  - The role of HIF-1 in up-regulating MICA expression on human renal proximal
      tubular epithelial cells during hypoxia/reoxygenation.
AB  - BACKGROUND: Human major histocompatibility complex class I-related chain A (MICA)
      plays a dual role in adaptive and innate immune responses. Increasing evidence
      demonstrates that MICA is closely correlated with acute and chronic kidney
      allograft rejection. Therefore, understanding the activation mechanisms of MICA
      is important in kidney transplantation. We previously demonstrated that
      ischemia/reperfusion injury (IRI) could up-regulate MICA expression on mouse
      kidney allografts. Since hypoxia-inducible factor-1 (HIF-1) is the master
      regulator of cellular adaptive responses to hypoxia during IRI, here we
      investigate whether HIF-1 could up-regulate MICA expression and its influence on
      NK cell cytotoxicity. RESULTS: We find that HIF-1alpha plays an important role in
      up-regulating MICA expression, inducing IFNgamma secretion and NK cell
      cytotoxicity during hypoxia/reoxygenation. First, we generated a HIF
      1alphaDELTAODD-expressing adenovirus to stably and functionally express HIF
      1alpha in human renal proximal tubular epithelial (HK-2) cells under normoxia
      conditions. HIF-1alpha over-expression in HK-2 cells induces MICA expression and
      enhances NK cell cytotoxic activity towards cells that express HIF-1alpha.
      Second, we used a hypoxia/reoxygenation cell model to simulate IRI in vitro and
      found that the suppression of HIF-1alpha by RNAi induces down-regulation of MICA
      expression and inhibits NK cytotoxicity. In antibody blocking experiments, an
      anti-MICA mAb was able to down-regulate NK cell cytotoxic activity towards HK-2
      cells that over-expressed HIF-1alpha. Moreover, when NK cells were co-cultured
      with the HK-2 cells expressing MICA, which was up-regulated by over-expression of
      HIF-1alpha, there was a significant increase in the secretion of IFNgamma. In the
      presence of the blocking MICA mAb, IFNgamma secretion was significantly
      decreased. CONCLUSIONS: These results demonstrate that hypoxia/reoxygenation
      promoted MICA expression on HK-2 cells is through a HIF-1 pathway. The increased
      IFNgamma secretion and enhanced NK cell cytotoxicity was mainly due to the
      surface expression of MICA induced by over-expression of HIF-1alpha. This study
      enhances our understanding of MICA activation mechanisms during kidney
      transplantation and provides insights into how IRI can influence transplant
      outcome. Moreover, these findings might be also important for developing
      strategies to reduce the effect of MICA in kidney transplant outcomes in the
      future.

PMID- 21092234
TI  - Identification and characterization of a novel fumarase gene by metagenome
      expression cloning from marine microorganisms.
AB  - BACKGROUND: Fumarase catalyzes the reversible hydration of fumarate to L-malate
      and is a key enzyme in the tricarboxylic acid (TCA) cycle and in amino acid
      metabolism. Fumarase is also used for the industrial production of L-malate from
      the substrate fumarate. Thermostable and high-activity fumarases from organisms
      that inhabit extreme environments may have great potential in industry,
      biotechnology, and basic research. The marine environment is highly complex and
      considered one of the main reservoirs of microbial diversity on the planet.
      However, most of the microorganisms are inaccessible in nature and are not easily
      cultivated in the laboratory. Metagenomic approaches provide a powerful tool to
      isolate and identify enzymes with novel biocatalytic activities for various
      biotechnological applications. RESULTS: A plasmid metagenomic library was
      constructed from uncultivated marine microorganisms within marine water samples.
      Through sequence-based screening of the DNA library, a gene encoding a novel
      fumarase (named FumF) was isolated. Amino acid sequence analysis revealed that
      the FumF protein shared the greatest homology with Class II fumarate hydratases
      from Bacteroides sp. 2_1_33B and Parabacteroides distasonis ATCC 8503 (26%
      identical and 43% similar). The putative fumarase gene was subcloned into pETBlue
      2 vector and expressed in E. coli BL21(DE3)pLysS. The recombinant protein was
      purified to homogeneity. Functional characterization by high performance liquid
      chromatography confirmed that the recombinant FumF protein catalyzed the
      hydration of fumarate to form L-malate. The maximum activity for FumF protein
      occurred at pH 8.5 and 55 degrees C in 5 mM Mg(2+). The enzyme showed higher
      affinity and catalytic efficiency under optimal reaction conditions: K(m) = 0.48
      mM, V(max) = 827 MUM/min/mg, and k(cat)/K(m) = 1900 mM/s. CONCLUSIONS: We
      isolated a novel fumarase gene, fumF, from a sequence-based screen of a plasmid
      metagenomic library from uncultivated marine microorganisms. The properties of
      FumF protein may be ideal for the industrial production of L-malate under higher
      temperature conditions. The identification of FumF underscores the potential of
      marine metagenome screening for novel biomolecules.

PMID- 21092235
TI  - Should helical tomotherapy replace brachytherapy for cervical cancer? Case
      report.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) administered via a helical
      tomotherapy (HT) system is an effective modality for treating lung cancer and
      metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative
      to brachytherapy in treatment of locally advanced cervical cancer in patients
      with unusual anatomic configurations of the uterus has never been studied. CASE
      PRESENTATION: A 46-year-old woman presented with an 8-month history of abnormal
      vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic
      resonance imaging (MRI) showed a cervical tumor with direct invasion of the right
      parametrium, bilateral hydronephrosis, and multiple uterine myomas. International
      Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was
      diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered
      via HT was administered instead of brachytherapy because of the presence of
      multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was
      performed after 6 weeks of treatment because of the presence of multiple uterine
      myomas. Neither pelvic MRI nor results of histopathologic examination at X-month
      follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting
      during treatment were noted. Lower gastrointestinal bleeding was noted at 14
      month follow-up. No fistula formation and no evidence of haematological,
      gastrointestinal or genitourinary toxicities were noted on the most recent follow
      up. CONCLUSIONS: CCRT followed by SBRT appears to be an effective and safe
      modality for treatment of cervical cancer. Larger-scale studies are warranted.

PMID- 21092236
TI  - Does epigenetic polymorphism contribute to phenotypic variances in Jatropha
      curcas L.?
AB  - BACKGROUND: There is a growing interest in Jatropha curcas L. (jatropha) as a
      biodiesel feedstock plant. Variations in its morphology and seed productivity
      have been well documented. However, there is the lack of systematic comparative
      evaluation of distinct collections under same climate and agronomic practices.
      With the several reports on low genetic diversity in jatropha collections, there
      is uncertainty on genetic contribution to jatropha morphology. RESULT: In this
      study, five populations of jatropha plants collected from China (CN), Indonesia
      (MD), Suriname (SU), Tanzania (AF) and India (TN) were planted in one farm under
      the same agronomic practices. Their agronomic traits (branching pattern, height,
      diameter of canopy, time to first flowering, dormancy, accumulated seed yield and
      oil content) were observed and tracked for two years. Significant variations were
      found for all the agronomic traits studied. Genetic diversity and epigenetic
      diversity were evaluated using florescence Amplified Fragment Length Polymorphism
      (fAFLP) and methylation sensitive florescence AFLP (MfAFLP) methods. Very low
      level of genetic diversity was detected (polymorphic band <0.1%) within and among
      populations. In contrast, intermediate but significant epigenetic diversity was
      detected (25.3% of bands were polymorphic) within and among populations. More
      than half of CCGG sites surveyed by MfAFLP were methylated with significant
      difference in inner cytosine and double cytosine methylation among populations.
      Principal coordinates analysis (PCoA) based on Nei's epigenetic distance showed
      Tanzania/India group distinct from China/Indonesia/Suriname group. Inheritance of
      epigenetic markers was assessed in one F1 hybrid population between two
      morphologically distinct parent plants and one selfed population. 30 out of 39
      polymorphic markers (77%) were found heritable and followed Mendelian
      segregation. One epiallele was further confirmed by bisulphite sequencing of its
      corresponding genomic region. CONCLUSION: Our study confirmed climate and
      practice independent differences in agronomic performance among jatropha
      collections. Such agronomic trait variations, however, were matched by very low
      genetic diversity and medium level but significant epigenetic diversity.
      Significant difference in inner cytosine and double cytosine methylation at CCGG
      sites was also found among populations. Most epigenetic differential markers can
      be inherited as epialleles following Mendelian segregation. These results suggest
      possible involvement of epigenetics in jatropha development.

PMID- 21092237
TI  - Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in
      oncology.
AB  - BACKGROUND: Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of
      vitamin D and a standard indicator of vitamin D status. Emerging evidence in the
      literature suggests a high prevalence of suboptimal vitamin D (as defined by
      serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum
      levels and higher mortality in cancer. We investigated the effect of oral vitamin
      D supplementation as a means for restoring suboptimal levels to optimal levels in
      cancer. METHODS: This is a retrospective observational study of 2198 cancer
      patients who had a baseline test prior to initiation of cancer therapy at our
      hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of
      their initial nutritional evaluation. Patients with baseline levels of < = 32
      ng/ml (n = 1651) were considered to have suboptimal serum 25(OH)D levels and were
      supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part
      of their nutritional care plan. The patients were retested at their first follow
      up visit. Of 1651 patients, 799 were available for follow up assessment. The mean
      serum 25(OH)D levels were compared in these 799 patients across the 2 time points
      (baseline and first follow-up) using paired sample t-test. We also investigated
      the factors associated with response to vitamin D supplementation. RESULTS: Of
      2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and
      treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean
      age at presentation was 55.4 years. The most common cancer types were breast
      (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and
      prostate (185, 8.4%). The mean time duration between baseline and first follow-up
      assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks).
      The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD =
      17.1) at baseline and first follow-up respectively; p < 0.001. Patients with
      prostate and lung cancer had the highest percentage of responders (70% and 69.2%
      respectively) while those with colorectal and pancreas had the lowest (46.7%
      each). Similarly, patients with serum levels 20-32 ng/ml at baseline were most
      likely to attain levels > 32 ng/ml compared to patients with baseline levels < 20
      ng/ml. CONCLUSIONS: The response to supplementation from suboptimal to optimal
      levels was greatest in patients with prostate and lung cancer as well as those
      with baseline levels between 20-32 ng/ml. Characteristics of non-responders as
      well as those who take longer to respond to supplementation need to be further
      studied and defined. Additionally, the impact of improved serum 25(OH)D levels on
      patient survival and quality of life needs to be investigated.

PMID- 21092238
TI  - Conserved charged amino acid residues in the extracellular region of
      sodium/iodide symporter are critical for iodide transport activity.
AB  - BACKGROUND: Sodium/iodide symporter (NIS) mediates the active transport and
      accumulation of iodide from the blood into the thyroid gland. His-226 located in
      the extracellular region of NIS has been demonstrated to be critical for iodide
      transport in our previous study. The conserved charged amino acid residues in the
      extracellular region of NIS were therefore characterized in this study. METHODS:
      Fourteen charged residues (Arg-9, Glu-79, Arg-82, Lys-86, Asp-163, His-226, Arg
      228, Asp-233, Asp-237, Arg-239, Arg-241, Asp-311, Asp-322, and Asp-331) were
      replaced by alanine. Iodide uptake abilities of mutants were evaluated by steady
      state and kinetic analysis. The three-dimensional comparative protein structure
      of NIS was further modeled using sodium/glucose transporter as the reference
      protein. RESULTS: All the NIS mutants were expressed normally in the cells and
      targeted correctly to the plasma membrane. However, these mutants, except R9A,
      displayed severe defects on the iodide uptake. Further kinetic analysis revealed
      that mutations at conserved positively charged amino acid residues in the
      extracellular region of NIS led to decrease NIS-mediated iodide uptake activity
      by reducing the maximal rate of iodide transport, while mutations at conserved
      negatively charged residues led to decrease iodide transport by increasing
      dissociation between NIS mutants and iodide. CONCLUSIONS: This is the first
      report characterizing thoroughly the functional significance of conserved charged
      amino acid residues in the extracellular region of NIS. Our data suggested that
      conserved charged amino acid residues, except Arg-9, in the extracellular region
      of NIS were critical for iodide transport.

PMID- 21092239
TI  - Echinacea-induced cytosolic Ca2+ elevation in HEK293.
AB  - BACKGROUND: With a traditional medical use for treatment of various ailments,
      herbal preparations of Echinacea are now popularly used to improve immune
      responses. One likely mode of action is that alkamides from Echinacea bind to
      cannabinoid type 2 (CB2) receptors and induce a transient increase in
      intracellular Ca2+. Here, we show that unidentified compounds from Echinacea
      purpurea induce cytosolic Ca2+ elevation in non-immune-related cells, which lack
      CB2 receptors and that the Ca2+ elevation is not influenced by alkamides.
      METHODS: A non-immune human cell line, HEK293, was chosen to evaluate E. purpurea
      root extracts and constituents as potential regulators of intracellular Ca2+
      levels. Changes in cytosolic Ca2+ levels were monitored and visualized by
      intracellular calcium imaging. U73122, a phospholipase C inhibitor, and 2
      aminoethoxydiphenyl borate (2-APB), an antagonist of inositol-1,4,5-trisphosphate
      (IP3) receptor, were tested to determine the mechanism of this Ca2+ signaling
      pathway. E. purpurea root ethanol extracts were fractionated by preparative HPLC,
      screened for bioactivity on HEK293 cells and by GC-MS for potential
      constituent(s) responsible for this bioactivity. RESULTS: A rapid transient
      increase in cytosolic Ca2+ levels occurs when E. purpurea extracts are applied to
      HEK293 cells. These stimulatory effects are phospholipase C and IP3 receptor
      dependent. Echinacea-evoked responses could not be blocked by SR 144528, a
      specific CB2 receptor antagonist, indicating that CB2 is not involved. Ca2+
      elevation is sustained after the Echinacea-induced Ca2+ release from
      intracellular Ca2+ stores; this longer-term effect is abolished by 2-APB,
      indicating a possible store operated calcium entry involvement. Of 28 HPLC
      fractions from E. purpurea root extracts, six induce cytosolic Ca2+ increase.
      Interestingly, GC-MS analysis of these fractions, as well as treatment of HEK293
      cells with known individual and combined chemicals, indicates the components
      thought to be responsible for the major immunomodulatory bioactivity of Echinacea
      do not explain the observed Ca2+ response. Rather, lipophilic constituents of
      unknown structures are associated with this bioactivity. CONCLUSIONS: Our data
      indicate that as yet unidentified constituents from Echinacea stimulate an IP3
      receptor and phospholipase C mediation of cytosolic Ca2+ levels in non-immune
      mammalian cells. This pathway is distinct from that induced in immune associated
      cells via the CB2 receptor.

PMID- 21092240
TI  - Initial experience of transumbilical laparoendoscopic single-site surgery of
      partial adrenalectomy in patient with aldosterone-producing adenoma.
AB  - BACKGROUND: Laparoscopic single-site surgery has recently emerged in the field of
      urology and this minimally-invasive surgery has resulted in a further reduction
      in morbidity compared with traditional laparoscopy. We present our initial
      experience with laparoendoscopic single-site surgery of partial adrenalectomy
      (LESS-PA) to treat aldosterone-producing adenomas. CASE PRESENTATION: A 60-year
      old woman was diagnosed with aldosterone-producing macroadenomas in the left
      adrenal and aldosterone-producing microadenomas in the right adrenal. A two-step
      operation was planned. The first step involved transumbilical LESS-PA for the
      left adrenal tumors. A multichannel port was inserted through the center of the
      umbilicus and the left adrenal gland was approached using bent instruments
      according to standard traditional laparoscopic procedures. The tumors were
      resected using an ultrasonic scalpel, and the resected site was coagulated using
      a vessel sealing instrument and then sealed with fibrin glue. Operative time was
      123 minutes and blood loss was minimal. The patient was discharged from hospital
      within 72 hours. Her right adrenal microadenomas will be treated in the next
      several months. CONCLUSIONS: Although our experience is limited, LESS-PA appears
      to be safe and feasible for treating aldosterone-producing adenomas. More cases
      and comparisons with the multiport technique are needed before drawing any
      definite conclusions concerning the technique.

PMID- 21092241
TI  - Molecular characterization of two distinct monopartite begomoviruses infecting
      tomato in India.
AB  - BACKGROUND: Tomato leaf curl viruses, which are the members of the genus
      Begomovirus, have emerged as devastating pathogens worldwide causing huge
      economic losses and threatening production of crops like cassava, cotton, grain
      legumes and vegetables. Even though the ToLCV isolates from Northern India have
      been shown to possess bipartite genome (designated as DNA A and DNA B), those
      from Australia, Taiwan and Southern India have a single genomic component (DNA
      A). We describe here the genetic diversity of two isolates of monopartite Tomato
      leaf curl virus infecting tomato in two extreme regions (North and South) of
      Indian subcontinent. RESULTS: The rolling circle amplification (RCA) products
      obtained from symptomatic samples were digested, cloned and sequenced. The
      complete DNA sequence of two Tomato leaf curl virus isolates identified as ToLCV
      CTM (India, New Delhi, 2005) and ToLCVK3/K5 (India, Kerala, 2008) are reported
      here. These isolates had the characteristic features of Begomovirus genome
      organization with six conserved open reading frames (ORFs). The ToLCV-K3 and
      ToLCV-K5 isolates may be the strains of the same virus since they show sequence
      homology of 97% over their entire genome. This, according to the guidelines
      established by the ICTV Geminiviridae Study-Group is higher than threshold (92%)
      for delineation of different viral variants and hence single, average value has
      been assigned for all their analyses presented here. The ToLCV-CTM and ToLCV
      K3/K5 viruses were found to be monopartite, as neither DNA-B component nor
      betasatellite associated with begomovirus species, were detected. The complete
      nucleotide sequence of DNA-A genome of CTM exhibited highest sequence homology
      (88%) to Croton yellow vein mosaic virus (AJ507777), and of isolates K3/K5
      (88.5%) to Tomato leaf curl Pakistan virus (DQ116884). This is less than the
      threshold value for demarcation of species in the genus Begomovirus. CONCLUSION:
      K3/K5 and CTM are considered to be novel isolates of Tomato leaf curl virus.
      Sequence analyses and phylogenetic study indicate that these two ToLCV isolates
      might have evolved by recombination between viruses related to two or more viral
      ancestors. The existence of different ToLCV isolates having high genome diversity
      in India poses a threat to the tomato production in the Asian continent.

PMID- 21092242
TI  - Alpha-1-acid glycoprotein as potential biomarker for alpha-fetoprotein-low
      hepatocellular carcinoma.
AB  - BACKGROUND: The outcome of patients with hepatocellular carcinoma (HCC) remains
      poor because of late diagnosis. We determined the performances of alpha -1-acid
      glycoprotein (AAG) and des-gamma-carboxy prothrombin (DCP) for the diagnosis of
      HCC, especially for alpha-fetoprotein (AFP)-low HCC. METHODS: Of the 220 patients
      included in this retrospective study, 124 had HCC, and 61 (49%) of these were AFP
      low HCC (AFP <= 20 ng/mL). The remaining 96 patients, including 49 with chronic
      hepatitis B or C and 47 with cirrhosis, were considered as control. Plasma AAG
      was analyzed using high performance liquid chromatography (HPLC) and confirmed
      using Western blot technique. RESULTS: When all patients with HCC were evaluated,
      the area under receiver operating characteristic (ROC) curves for AAG (0.94, 95%
      CI: 0.91-0.97) and DCP (0.92, 95% CI: 0.88-0.95) were similar (P = 0.40). AAG had
      better area under ROC curve (0.96, 95% CI: 0.94-0.99) than DCP (0.87, 95% CI:
      0.81-0.93) for AFP-low HCC (P < 0.05). At the specificity 95%, the sensitivity of
      AAG was higher in AFP-low HCC than in AFP-high HCC (82% and 62%, respectively).
      In contrast, higher sensitivity was obtained from DCP in discriminating HCC
      patients with low AFP than that in high AFP (57% and 90%, respectively).
      CONCLUSION: Our cross-sectional study showed that AAG was better performance in
      diagnosing HCC patients with low AFP, while DCP did better in those with high
      AFP.

PMID- 21092243
TI  - Proteomic approach with LCMS-IT-TOF identified an increase of Rab33B after
      transient focal cerebral ischemia in mice.
AB  - BACKGROUND: Several proteins are known to be markedly expressed in the brain
      during cerebral ischemia; however, the changes in protein profiles within the
      ischemic brain after an ischemic insult have not been fully elucidated. We
      studied the changes in the ischemic brain proteome after focal cerebral ischemia,
      induced by middle cerebral artery occlusion (MCAO) in mice. METHODS: LCMS-IT-TOF
      mass spectrometry was used to detect the changes in ischemic brain protein
      patterns after MCAO. We evaluated the protein expression detected in the ischemic
      area, by western blotting and immunohistochemistry. RESULTS: Nine unique proteins
      were identified from the ischemic area at 10 h after ischemic insult. Among these
      proteins, we focused on Rab33b, a member of RAS oncogene family and we found that
      Rab33b was up-regulated in the ischemic striatum and the number of Rab33B
      positive cells increased in a time-dependent manner. Rab33B colocalized with Iba
      1 positive microglia in the ischemic area. CONCLUSION: These findings suggest
      that LCMS-IT-TOF is useful for identifying changes in proteins after cerebral
      ischemia and that Rab33B is partially related to the pathogenesis of transient
      cerebral ischemia in mice.

PMID- 21092244
TI  - Involvement of microRNAs in physiological and pathological processes in the lung.
AB  - To date, at least 900 different microRNA (miRNA) genes have been discovered in
      the human genome. These short, single-stranded RNA molecules originate from
      larger precursor molecules that fold to produce hairpin structures, which are
      subsequently processed by ribonucleases Drosha/Pasha and Dicer to form mature
      miRNAs. MiRNAs play role in the posttranscriptional regulation of about one third
      of human genes, mainly via degradation of target mRNAs. Whereas the target mRNAs
      are often involved in the regulation of diverse physiological processes ranging
      from developmental timing to apoptosis, miRNAs have a strong potential to
      regulate fundamental biological processes also in the lung compartment. However,
      the knowledge of the role of miRNAs in physiological and pathological conditions
      in the lung is still limited. This review, therefore, summarizes current
      knowledge of the mechanism, function of miRNAs and their contribution to lung
      development and homeostasis. Besides the involvement of miRNAs in pulmonary
      physiological conditions, there is evidence that abnormal miRNA expression may
      lead to pathological processes and development of various pulmonary diseases.
      Next, the review describes current state-of-art on the miRNA expression profiles
      in smoking-related diseases including lung cancerogenesis, in immune system
      mediated pulmonary diseases and fibrotic processes in the lung. From the current
      research it is evident that miRNAs may play role in the posttranscriptional
      regulation of key genes in human pulmonary diseases. Further studies are,
      therefore, necessary to explore miRNA expression profiles and their association
      with target mRNAs in human pulmonary diseases.

PMID- 21092247
TI  - Decrease in seroprevalence of hepatitis A after the implementation of nationwide
      disposable tableware use in Taiwan.
AB  - BACKGROUND: Taiwan is an endemic area of viral hepatitis, including hepatitis A,
      which is transmitted mainly from the fecal-oral route. In order to reduce the
      transmission through food intake, the government implemented a policy of
      nationwide disposal tableware use in public eating places in 1982. We conducted a
      study to estimate the seroprevalence of Hepatitis A in a group of workers in
      Taiwan in 2005, determine the risk factors, and compare seroprevalence to
      published estimates in Taiwan to evaluate changes in the seroprevalence after the
      implementation of the nationwide disposal tableware use. METHODS: We recruited
      workers of an industrial park during their annual health examinations in 2005 and
      measured their anti-hepatitis A virus IgG titer using microparticle enzyme
      immunoassay. We compared the seroprevalence across different birth cohorts within
      the study population and also analyzed data from previous studies. RESULTS: The
      overall sero-positive rate was 22.0% in the 11,777 participants. The rate was
      much lower among those who were covered by the program since birth (born after
      1982) in comparison with those who were not (2.7% vs. 25.3%, p < 0.001). From the
      analyses of data from previous studies, we found the age-specific rates were
      similar in cohorts born in or after 1982 across studies conducted in different
      time periods but decreased with the calendar year in cohorts born before 1982. In
      particular, the age-specific seroprevalence dropped to less than one third in a
      three-year period among those who were born around 1982. CONCLUSIONS: Data from
      both the current and previous studies in different time periods supported the
      effectiveness of disposal tableware in preventing the transmission of hepatitis
      A.

PMID- 21092245
TI  - LAB-Secretome: a genome-scale comparative analysis of the predicted extracellular
      and surface-associated proteins of Lactic Acid Bacteria.
AB  - BACKGROUND: In Lactic Acid Bacteria (LAB), the extracellular and surface
      associated proteins can be involved in processes such as cell wall metabolism,
      degradation and uptake of nutrients, communication and binding to substrates or
      hosts. A genome-scale comparative study of these proteins (secretomes) can
      provide vast information towards the understanding of the molecular evolution,
      diversity, function and adaptation of LAB to their specific environmental niches.
      RESULTS: We have performed an extensive prediction and comparison of the
      secretomes from 26 sequenced LAB genomes. A new approach to detect homolog
      clusters of secretome proteins (LaCOGs) was designed by integrating protein
      subcellular location prediction and homology clustering methods. The initial
      clusters were further adjusted semi-manually based on multiple sequence
      alignments, domain compositions, pseudogene analysis and biological function of
      the proteins. Ubiquitous protein families were identified, as well as species
      specific, strain-specific, and niche-specific LaCOGs. Comparative analysis of
      protein subfamilies has shown that the distribution and functional specificity of
      LaCOGs could be used to explain many niche-specific phenotypes.A comprehensive
      and user-friendly database LAB-Secretome was constructed to store, visualize and
      update the extracellular proteins and LaCOGs
      http://www.cmbi.ru.nl/lab_secretome/. This database will be updated regularly
      when new bacterial genomes become available. CONCLUSIONS: The LAB-Secretome
      database could be used to understand the evolution and adaptation of lactic acid
      bacteria to their environmental niches, to improve protein functional annotation
      and to serve as basis for targeted experimental studies.

PMID- 21092248
TI  - Allotment gardening and health: a comparative survey among allotment gardeners
      and their neighbors without an allotment.
AB  - BACKGROUND: The potential contribution of allotment gardens to a healthy and
      active life-style is increasingly recognized, especially for elderly populations.
      However, few studies have empirically examined beneficial effects of allotment
      gardening. In the present study the health, well-being and physical activity of
      older and younger allotment gardeners was compared to that of controls without an
      allotment. METHODS: A survey was conducted among 121 members of 12 allotment
      sites in the Netherlands and a control group of 63 respondents without an
      allotment garden living next to the home addresses of allotment gardeners. The
      survey included five self-reported health measures (perceived general health,
      acute health complaints, physical constraints, chronic illnesses, and
      consultations with GP), four self-reported well-being measures (stress, life
      satisfaction, loneliness, and social contacts with friends) and one measure
      assessing self-reported levels of physical activity in summer. Respondents were
      divided into a younger and older group at the median of 62 years which equals the
      average retirement age in the Netherlands. RESULTS: After adjusting for income,
      education level, gender, stressful life events, physical activity in winter, and
      access to a garden at home as covariates, both younger and older allotment
      gardeners reported higher levels of physical activity during the summer than
      neighbors in corresponding age categories. The impacts of allotment gardening on
      health and well-being were moderated by age. Allotment gardeners of 62 years and
      older scored significantly or marginally better on all measures of health and
      well-being than neighbors in the same age category. Health and well-being of
      younger allotment gardeners did not differ from younger neighbors. The greater
      health and well-being benefits of allotment gardening for older gardeners may be
      related to the finding that older allotment gardeners were more oriented towards
      gardening and being active, and less towards passive relaxation. CONCLUSIONS:
      These findings are consistent with the notion that having an allotment garden may
      promote an active life-style and contribute to healthy aging. However, the
      findings may be limited by self selection and additional research is needed to
      confirm and extend the current findings.

PMID- 21092249
TI  - Epigenetic control of the basal-like gene expression profile via Interleukin-6 in
      breast cancer cells.
AB  - BACKGROUND: Basal-like carcinoma are aggressive breast cancers that frequently
      carry p53 inactivating mutations, lack estrogen receptor-alpha (ERalpha) and
      express the cancer stem cell markers CD133 and CD44. These tumors also over
      express Interleukin 6 (IL-6), a pro-inflammatory cytokine that stimulates the
      growth of breast cancer stem/progenitor cells. RESULTS: Here we show that p53
      deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal
      promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits
      the loss of methylation at the CD133 promoter region 1 and of CD44 proximal
      promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces
      the methylation of estrogen receptor (ERalpha) promoter and the loss of ERalpha
      mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter
      and of CD133 promoter region 2, which harbour putative repressor regions.
      CONCLUSION: We conclude that IL-6, whose methylation-dependent autocrine loop is
      triggered by the inactivation of p53, induces an epigenetic reprogramming that
      drives breast carcinoma cells towards a basal-like/stem cell-like gene expression
      profile.

PMID- 21092250
TI  - Supply sensitive services in Swiss ambulatory care: an analysis of basic health
      insurance records for 2003-2007.
AB  - BACKGROUND: Swiss ambulatory care is characterized by independent, and primarily
      practice-based, physicians, receiving fee for service reimbursement. This study
      analyses supply sensitive services using ambulatory care claims data from
      mandatory health insurance. A first research question was aimed at the hypothesis
      that physicians with large patient lists decrease their intensity of services and
      bill less per patient to health insurance, and vice versa: physicians with
      smaller patient lists compensate for the lack of patients with additional visits
      and services. A second research question relates to the fact that several cantons
      are allowing physicians to directly dispense drugs to patients ('self
      dispensation') whereas other cantons restrict such direct sales to emergencies
      only. This second question was based on the assumption that patterns of
      rescheduling patients for consultations may differ across channels of dispensing
      prescription drugs and therefore the hypothesis of different consultation costs
      in this context was investigated. METHODS: Complete claims data paid for by
      mandatory health insurance of all Swiss physicians in own practices were analyzed
      for the years 2003-2007. Medical specialties were pooled into six main provider
      types in ambulatory care: primary care, pediatrics, gynecology & obstetrics,
      psychiatrists, invasive and non-invasive specialists. For each provider type,
      regression models at the physician level were used to analyze the relationship
      between the number of patients treated and the total sum of treatment cost
      reimbursed by mandatory health insurance. RESULTS: The results show non
      proportional relationships between patient numbers and total sum of treatment
      cost for all provider types involved implying that treatment costs per patient
      increase with higher practice size. The related additional costs to the health
      system are substantial. Regions with self-dispensation had lowest treatment cost
      for primary care, gynecology, pediatrics and for psychiatrists whereas
      "prescription only" areas had lowest cost for specialists with non-invasive and
      invasive activities. CONCLUSIONS: The results indicate that payment methods for
      services and for prescription drugs are associated with variations in treatment
      cost that are unlikely warranted by different medical needs of patients alone.
      Promoting physician accountability of care by linking reimbursements to quality,
      not quantity, of services are important policy measures to be considered for
      health care in Switzerland.

PMID- 21092251
TI  - Increased prevalence of vulnerable atherosclerotic plaques and low levels of
      natural IgM antibodies against phosphorylcholine in patients with systemic lupus
      erythematosus.
AB  - INTRODUCTION: The risk of cardiovascular disease (CVD) and atherosclerosis is
      reported to be increased in systemic lupus erythematosus (SLE). We recently
      reported a negative association between natural IgM-antibodies against
      phosphorylcholine (anti-PC) in the general population, high anti-PC levels
      leading to decreased atherosclerosis development and low levels to increased risk
      of CVD. Potential mechanisms include anti-inflammatory properties and inhibition
      of uptake of oxidized low density lipoprotein (LDL) in macrophages. The objective
      herein was to study atherosclerosis in SLE in detail and in relation to
      traditional and non-traditional risk factors. METHODS: A total of 114 patients
      with SLE were compared with 122 age- and sex-matched population-based controls.
      Common carotid intima-media thickness (IMT), calculated intima-media area (cIMa)
      and plaque occurrence were determined by B-mode ultrasound as a surrogate measure
      of atherosclerosis. Plaques were graded according to echogenicity and grouped as
      1 to 4, with 1 being echoluscent, and considered most vulnerable. Anti-PC was
      studied by ELISA. RESULTS: Hypertension, triglycerides and insulin resistance
      (determined by homeostasis model assessment of insulin resistance) and C-reactive
      protein (CRP) were increased in SLE (P < 0.01) while smoking, LDL, high density
      lipoprotein (HDL) did not differ between groups. Low levels of anti-PC IgM
      (lowest tertile) were more common in SLE patients than in controls (P = 0.0022).
      IMT and cIMa did not differ significantly between groups. However, plaques were
      more often found in SLE patients (P = 0.029). Age, LDL and IgM anti-PC (lowest
      tertile) were independently associated with plaque occurrence in SLE. Further, in
      the left carotid arteries echoluscent plaques (grade 1) were more prevalent in
      SLE as compared to controls (P < 0.016). CONCLUSIONS: Plaque occurrence in the
      carotid arteries is increased in SLE and is independently associated with age,
      LDL and low anti-PC levels. Vulnerable plaques were more common in SLE. Anti-PC
      could be a novel risk marker also with a therapeutic potential in SLE.

PMID- 21092252
TI  - Validation of a new transpulmonary thermodilution system to assess global end
      diastolic volume and extravascular lung water.
AB  - INTRODUCTION: A new system has been developed to assess global end-diastolic
      volume (GEDV), a volumetric marker of cardiac preload, and extravascular lung
      water (EVLW) from a transpulmonary thermodilution curve. Our goal was to compare
      this new system with the system currently in clinical use. METHODS: Eleven
      anesthetized and mechanically ventilated pigs were instrumented with a central
      venous catheter and a right (PulsioCath; Pulsion, Munich, Germany) and a left
      (VolumeViewTM; Edwards Lifesciences, Irvine, CA, USA) thermistor-tipped femoral
      arterial catheter. The right femoral catheter was used to measure GEDV and EVLW
      using the PiCCO(2)TM (Pulsion) method (GEDV(1) and EVLW(1), respectively). The
      left femoral catheter was used to measure the same parameters using the new
      VolumeViewTM (Edwards Lifesciences) method (GEDV(2) and EVLW(2), respectively).
      Measurements were made during inotropic stimulation (dobutamine), during
      hypovolemia (bleeding), during hypervolemia (fluid overload), and after inducing
      acute lung injury (intravenous oleic acid). RESULTS: One hundred and thirty-seven
      paired measurements were analyzed. GEDV(1) and GEDV(2) ranged from 701 to 1,629
      ml and from 774 to 1,645 ml, respectively. GEDV(1) and GEDV(2) were closely
      correlated (r(2) = 0.79), with mean bias of -11 +/- 80 ml and percentage error of
      14%. EVLW(1) and EVLW(2) ranged from 507 to 2,379 ml and from 495 to 2,222 ml,
      respectively. EVLW(1) and EVLW(2) were closely correlated (r(2) = 0.97), with
      mean bias of -5 +/- 72 ml and percentage error of 15%. CONCLUSIONS: In animals,
      and over a very wide range of values, a good agreement was found between the new
      VolumeViewTM system and the PiCCOTM system to assess GEDV and EVLW.

PMID- 21092253
TI  - Enrichment of ultraconserved elements among genomic imbalances causing mental
      delay and congenital anomalies.
AB  - BACKGROUND: The ultraconserved elements (UCEs) are defined as stretches of at
      least 200 base pairs of human DNA that match identically with corresponding
      regions in the mouse and rat genomes, albeit their real significance remains an
      intriguing issue. These elements are most often located either overlapping exons
      in genes involved in RNA processing or in introns or nearby genes involved in the
      regulation of transcription and development. Interestingly, human UCEs have been
      reported to be strongly depleted among segmental duplications and benign copy
      number variants (CNVs). However no comprehensive survey of a putative enrichment
      of these elements among pathogenic dose variants has yet been reported. RESULTS:
      A survey for UCEs was performed among the 26 cryptic genomic rearrangements
      detected in our series of 200 patients with idiopathic neurodevelopmental
      disorders associated to congenital anomalies. A total of 29 elements, out of the
      481 described UCEs, were contained in 13 of the 26 pathogenic gains or losses
      detected in our series, what represents a highly significant enrichment of
      ultraconserved elements. In addition, here we show that these elements are
      preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in
      duplications), and that this association is not related with a higher content of
      genes. In contrast, pathogenic CNVs lacking UCEs showed almost a threefold higher
      content in genes. CONCLUSIONS: We propose that these elements may be interpreted
      as hallmarks for dose-sensitive genes, particularly for those genes whose gain or
      loss may be directly implied in neurodevelopmental disorders. Therefore, their
      presence in genomic imbalances of unknown effect might be suggestive of a
      clinically relevant condition.

PMID- 21092254
TI  - Multiple infarcted regenerative nodules in liver cirrhosis after decompensation
      of cirrhosis: a case series.
AB  - INTRODUCTION: Liver cirrhosis is a common disease with many known complications.
      Cirrhosis represents a clinical spectrum, ranging from asymptomatic liver disease
      to hepatic decompensation. Manifestations of hepatic decompensation include
      variceal bleeding, ascites, hepatic encephalopathy, hepatorenal syndrome,
      hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular
      carcinoma. There are reports about infarcted regenerative nodules in cirrhotic
      livers after gastrointestinal hemorrhage. CASE PRESENTATION: We report three
      Caucasian patients (one female and two male patients; ages: 52, 54 and 60 years)
      with decompensated liver cirrhosis, who showed newly infarcted regenerative
      nodules at necropsy. Two of them suffered from gastric variceal bleeding.
      Histopathology showed extensive infarction in all three cases.Hemorrhage and
      inflammatory changes were also observed around the infarcted regenerative
      nodules. CONCLUSION: These patients showed focal liver lesions, to be considered
      in the differential diagnosis of cirrhotic livers. Infarcted regenerative nodules
      may be underdiagnosed in patients with decompensation of cirrhosis. In order to
      differentiate these lesions from malignant tumors, serial imaging seems to be
      helpful. However, the main differential diagnosis should be an abscess. It is
      important to know the wide spectrum of image appearances of these lesions.
      Hypotension can lead to a reduction of portal and arterial liver flow. Since
      variceal bleeding or septic shock can induce hypotension - as observed in our
      patients - we conclude that this leads to infarction of such nodules.

PMID- 21092255
TI  - Reticular alignment: a progressive corner-cutting method for multiple sequence
      alignment.
AB  - BACKGROUND: In this paper, we introduce a progressive corner cutting method
      called Reticular Alignment for multiple sequence alignment. Unlike previous
      corner-cutting methods, our approach does not define a compact part of the
      dynamic programming table. Instead, it defines a set of optimal and suboptimal
      alignments at each step during the progressive alignment. The set of alignments
      are represented with a network to store them and use them during the progressive
      alignment in an efficient way. The program contains a threshold parameter on
      which the size of the network depends. The larger the threshold parameter and
      thus the network, the deeper the search in the alignment space for better scored
      alignments. RESULTS: We implemented the program in the Java programming language,
      and tested it on the BAliBASE database. Reticular Alignment can outperform
      ClustalW even if a very simple scoring scheme (BLOSUM62 and affine gap penalty)
      is implemented and merely the threshold value is increased. However, this set-up
      is not sufficient for outperforming other cutting-edge alignment methods. On the
      other hand, the reticular alignment search strategy together with sophisticated
      scoring schemes (for example, differentiating gap penalties for hydrophobic and
      hydrophylic amino acids) overcome FSA and in some accuracy measurement, even
      MAFFT. The program is available from http://phylogeny-cafe.elte.hu/RetAlign/
      CONCLUSIONS: Reticular alignment is an efficient search strategy for finding
      accurate multiple alignments. The highest accuracy achieved when this searching
      strategy is combined with sophisticated scoring schemes.

PMID- 21092256
TI  - Is advanced life support better than basic life support in prehospital care? A
      systematic review.
AB  - BACKGROUND: Prehospital care is classified into ALS- (advanced life support) and
      BLS- (basic life support) levels according to the methods used. ALS-level
      prehospital care uses invasive methods, such as intravenous fluids, medications
      and intubation. However, the effectiveness of ALS care compared to BLS has been
      questionable. AIM: The aim of this systematic review is to compare the
      effectiveness of ALS- and BLS-level prehospital care. MATERIAL AND METHODS: In a
      systematic review, articles where ALS-level prehospital care was compared to BLS
      level or any other treatment were included. The outcome variables were mortality
      or patient's health-related quality of life or patient's capacity to perform
      daily activities. RESULTS: We identified 46 articles, mostly retrospective
      observational studies. The results on the effectiveness of ALS in unselected
      patient cohorts are contradictory. In cardiac arrest, early cardiopulmonary
      resuscitation and defibrillation are essential for survival, but prehospital ALS
      interventions have not improved survival. Prehospital thrombolytic treatment
      reduces mortality in patients having a myocardial infarction. The majority of
      research into trauma favours BLS in the case of penetrating trauma and also in
      cases of short distance to a hospital. In patients with severe head injuries, ALS
      provided by paramedics and intubation without anaesthesia can even be harmful. If
      the prehospital care is provided by an experienced physician and by a HEMS
      organisation (Helicopter Emergency Medical Service), ALS interventions may be
      beneficial for patients with multiple injuries and severe brain injuries.
      However, the results are contradictory. CONCLUSIONS: ALS seems to improve
      survival in patients with myocardial infarction and BLS seems to be the proper
      level of care for patients with penetrating injuries. Some studies indicate a
      beneficial effect of ALS among patients with blunt head injuries or multiple
      injuries. There is also some evidence in favour of ALS among patients with
      epileptic seizures as well as those with a respiratory distress.

PMID- 21092257
TI  - Cystatin M loss is associated with the losses of estrogen receptor, progesterone
      receptor, and HER4 in invasive breast cancer.
AB  - INTRODUCTION: This study was aimed at understanding the clinicopathological
      significance of cystatin M loss, and investigating possible factors responsible
      for cystatin M loss in breast cancer. METHODS: The expression of estrogen
      receptor (ER), progesterone receptor (PR), HER2, HER4, and cystatin M was
      retrospectively analyzed using immunohistochemistry in 117 patients with ductal
      carcinoma in situ (DCIS) and in 175 patients with invasive breast cancer (IBC).
      The methylation status of CST6 gene encoding cystatin M was evaluated using
      methylation-specific polymerase chain reaction (PCR) in formalin-fixed paraffin
      embedded tissues from 292 participants and using pyrosequencing in fresh-frozen
      tumor and matched normal tissues from 51 IBC patients. RESULTS: Cystatin M loss
      was found in 9 (8%) of 117 patients with DCIS and in 99 (57%) of 175 with
      invasive breast cancer (IBC) (P < 0.0001). Cystatin M loss was found in 58 (57%)
      of 101 HER2-negative IBCs and in 41 (55%) of 74 HER2-positive IBCs, and this
      difference was not statistically significant (P = 0.97). However, cystatin M loss
      was significantly associated with the loss of ER (P = 0.01), PR (P = 0.002), and
      HER4 (P = 0.003) in IBCs. Cystatin M loss occurred in 34 (76%) of the 45 HER4
      negative IBCs and in 65 (50%) of the 130 HER4-positive IBCs. Multivariate
      analysis showed that cystatin M loss occurred at a 3.57 times (95% CI = 1.28 to
      9.98; P = 0.01) higher prevalence in the triple-negative IBCs of ER, PR, and HER4
      than in other subtypes, after adjusting for age. The quantity of CST6 methylation
      was associated with ER loss (P = 0.0002) in IBCs but not with the loss of PR (P =
      0.64) or HER4 (P = 0.87). CONCLUSIONS: The present study suggests that cystatin M
      loss may be associated with the losses of ER, PR, and HER4 in IBC.

PMID- 21092258
TI  - Effects of Kurozu concentrated liquid on adipocyte size in rats.
AB  - BACKGROUND: Kurozu concentrated liquid (KCL) is used as a health-promoting
      supplement for the treatment of disorders such as cancer, hyperlipidemia, and
      hypertension in Japan. We investigated the possible anti-obesity effects of KCL
      in rats. METHODS: Male Sprague Dawley rats were fed American Institute of
      Nutrition 76 formula diet and were orally administrated KCL or acetic acid at a
      dose of 100 mg/kg body weight or deionized water for 4 weeks. Adipocyte size, DNA
      content in subcutaneous adipose tissue, lipid levels in the serum and liver, and
      the rate of fatty acid excretion were determined. Effects of KCL on pancreatic
      lipase activity and 3T3-L1 preadipocyte differentiation were investigated in
      vitro. RESULTS: In the KCL group, the average adipocyte size in subcutaneous and
      perirenal adipose tissues was significantly reduced. The KCL-administered rats
      displayed greater numbers of small adipocytes in the subcutaneous, perirenal and
      mesenteric adipose tissues than did rats from the other groups. In the KCL group,
      the DNA content in subcutaneous adipose tissue was significantly increased. The
      rate of fatty acid excretion was significantly increased in the KCL group.
      Furthermore, KCL significantly inhibited pancreatic lipase activity in vitro, and
      also significantly inhibited fat accumulation and mRNA expression of fatty acid
      binding protein 2 (aP2) and peroxisome proliferator-activated gamma (PPARgamma)
      in 3T3-L1 preadipocyte. The levels of serum and liver lipids, the concentration
      of serum glucose, and the levels of adiponectin were similar among the 3 groups.
      CONCLUSION: Oral administration of KCL decreases the adipocyte size via
      inhibition of dietary fat absorption and reductions of PPARgamma and aP2 mRNA
      expression levels in adipocytes.

PMID- 21092259
TI  - Independent evolution of the core and accessory gene sets in the genus Neisseria:
      insights gained from the genome of Neisseria lactamica isolate 020-06.
AB  - BACKGROUND: The genus Neisseria contains two important yet very different
      pathogens, N. meningitidis and N. gonorrhoeae, in addition to non-pathogenic
      species, of which N. lactamica is the best characterized. Genomic comparisons of
      these three bacteria will provide insights into the mechanisms and evolution of
      pathogenesis in this group of organisms, which are applicable to understanding
      these processes more generally. RESULTS: Non-pathogenic N. lactamica exhibits
      very similar population structure and levels of diversity to the meningococcus,
      whilst gonococci are essentially recent descendents of a single clone. All three
      species share a common core gene set estimated to comprise around 1190 CDSs,
      corresponding to about 60% of the genome. However, some of the nucleotide
      sequence diversity within this core genome is particular to each group,
      indicating that cross-species recombination is rare in this shared core gene set.
      Other than the meningococcal cps region, which encodes the polysaccharide
      capsule, relatively few members of the large accessory gene pool are exclusive to
      one species group, and cross-species recombination within this accessory genome
      is frequent. CONCLUSION: The three Neisseria species groups represent coherent
      biological and genetic groupings which appear to be maintained by low rates of
      inter-species horizontal genetic exchange within the core genome. There is
      extensive evidence for exchange among positively selected genes and the accessory
      genome and some evidence of hitch-hiking of housekeeping genes with other loci.
      It is not possible to define a 'pathogenome' for this group of organisms and the
      disease causing phenotypes are therefore likely to be complex, polygenic, and
      different among the various disease-associated phenotypes observed.

PMID- 21092260
TI  - Combining nitric oxide release with anti-inflammatory activity preserves
      nigrostriatal dopaminergic innervation and prevents motor impairment in a 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.
AB  - BACKGROUND: Current evidence suggests a role of neuroinflammation in the
      pathogenesis of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) model of basal ganglia injury. Reportedly, nonsteroidal
      anti-inflammatory drugs (NSAIDs) mitigate DAergic neurotoxicity in rodent models
      of PD. Consistent with these findings, epidemiological analysis indicated that
      certain NSAIDs may prevent or delay the progression of PD. However, a serious
      impediment of chronic NSAID therapy, particularly in the elderly, is gastric,
      renal and cardiac toxicity. Nitric oxide (NO)-donating NSAIDs, have a safer
      profile while maintaining anti-inflammatory activity of parent compounds. We have
      investigated the oral activity of the NO-donating derivative of flurbiprofen, [2
      fluoro-alpha-methyl (1,1'-biphenyl)-4-acetic-4-(nitrooxy)butyl ester], HCT1026
      (30 mg kg(-1) daily in rodent chow) in mice exposed to the parkinsonian
      neurotoxin MPTP. METHODS: Ageing mice were fed with a control, flurbiprofen, or
      HCT1026 diet starting ten days before MPTP administration and continuing for all
      the experimental period. Striatal high affinity synaptosomal dopamine up-take,
      motor coordination assessed with the rotarod, tyrosine hydroxylase (TH)- and
      dopamine transporter (DAT) fiber staining, stereological cell counts,
      immunoblotting and gene expression analyses were used to assess MPTP-induced
      nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP. RESULTS:
      HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas
      flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026
      efficiently counteracted motor impairment and reversed MPTP-induced decreased
      synaptosomal [3H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH+
      neuron loss in substantia nigra pars compacta (SNpc), as opposed to age-matched
      mice fed with a control diet. These effects were associated to a significant
      decrease in reactive macrophage antigen-1 (Mac-1)-positive microglial cells
      within the striatum and ventral midbrain, decreased expression of iNOS, Mac-1 and
      NADPH oxidase (PHOX), and downregulation of 3-Nitrotyrosine, a peroxynitrite
      finger print, in SNpc DAergic neurons. CONCLUSIONS: Oral treatment with HCT1026
      has a safe profile and a significant efficacy in counteracting MPTP-induced
      dopaminergic (DAergic) neurotoxicity, motor impairment and microglia activation
      in ageing mice. HCT1026 provides a novel promising approach towards the
      development of effective pharmacological neuroprotective strategies against PD.

PMID- 21092262
TI  - Development of a duodenal gallstone ileus with gastric outlet obstruction
      (Bouveret syndrome) four months after successful treatment of symptomatic
      gallstone disease with cholecystitis and cholangitis: a case report.
AB  - INTRODUCTION: Cases of gallstone ileus account for 1% to 4% of all instances of
      mechanical bowel obstruction. The majority of obstructing gallstones are located
      in the terminal ileum. Less than 10% of impacted gallstones are located in the
      duodenum. A gastric outlet obstruction secondary to a gallstone ileus is known as
      Bouveret syndrome. Gallstones usually enter the bowel through a biliary enteral
      fistula. Little is known about the formation of such fistulae in the course of
      gallstone disease. CASE PRESENTATION: We report the case of a 72-year-old
      Caucasian woman born in Germany with a gastric outlet obstruction due to a
      gallstone ileus (Bouveret syndrome), with a large gallstone impacted in the third
      part of the duodenum. Diagnostic investigations of our patient included plain
      abdominal films, gastroscopy and abdominal computed tomography, which showed a
      biliary enteric fistula between the gallbladder and the duodenal bulb. Our
      patient was successfully treated by laparotomy, duodenotomy, extraction of the
      stone, cholecystectomy, and resection of the fistula in a one-stage surgical
      approach. Histopathological examination showed chronic and acute cholecystitis,
      with perforated ulceration of the duodenal wall and acute purulent inflammation
      of the surrounding fatty tissue. Four months prior to developing a gallstone
      ileus our patient had been hospitalized for cholecystitis, a large gallstone in
      the gallbladder, cholangitis and a small obstructing gallstone in the common
      biliary duct. She had been treated with endoscopic retrograde
      cholangiopancreatography, endoscopic biliary sphincterotomy, balloon extraction
      of the common biliary duct gallstone, and intravenous antibiotics. At the time of
      her first presentation, abdominal ultrasound and endoscopic examination
      (including esophagogastroduodenoscopy and endoscopic retrograde
      cholangiopancreatography) had not shown any evidence of a biliary enteral
      fistula. In the four months preceding the gallstone ileus our patient had been
      asymptomatic. CONCLUSION: In patients known to have gallstone disease presenting
      with symptoms of ileus, the differential diagnosis of a gallstone ileus should be
      considered even in the absence of preceding symptoms related to the gallbladder
      disease. Gallstones large enough to cause intestinal obstruction usually enter
      the bowel by a biliary enteral fistula. During the formation of such a fistula,
      patients can be asymptomatic.

PMID- 21092261
TI  - How large are the nonspecific effects of acupuncture? A meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: While several recent large randomized trials found clinically
      relevant effects of acupuncture over no treatment or routine care, blinded trials
      comparing acupuncture to sham interventions often reported only minor or no
      differences. This raises the question whether (sham) acupuncture is associated
      with particularly potent nonspecific effects. We aimed to investigate the size of
      nonspecific effects associated with acupuncture interventions. METHODS: MEDLINE,
      Embase, Cochrane Central Register of Controlled Clinical Trials and reference
      lists were searched up to April 2010 to identify randomized trials of acupuncture
      for any condition, including both sham and no acupuncture control groups. Data
      were extracted by one reviewer and verified by a second. Pooled standardized mean
      differences were calculated using a random effects model with the inverse
      variance method. RESULTS: Thirty-seven trials with a total of 5754 patients met
      the inclusion criteria. The included studies varied strongly regarding patients,
      interventions, outcome measures, methodological quality and effect sizes
      reported. Among the 32 trials reporting a continuous outcome measure, the random
      effects standardized mean difference between sham acupuncture and no acupuncture
      groups was -0.45 (95% confidence interval, -0.57, -0.34; I2 = 54%; Egger's test
      for funnel plot asymmetry, P = 0.25). Trials with larger effects of sham over no
      acupuncture reported smaller effects of acupuncture over sham intervention than
      trials with smaller nonspecific effects (beta = -0.39, P = 0.029). CONCLUSIONS:
      Sham acupuncture interventions are often associated with moderately large
      nonspecific effects which could make it difficult to detect small additional
      specific effects. Compared to inert placebo interventions, effects associated
      with sham acupuncture might be larger, which would have considerable implications
      for the design and interpretation of clinical trials.

PMID- 21092263
TI  - Effects of Hypericum Perforatum, in a rodent model of periodontitis.
AB  - BACKGROUND: Hypericum perforatum is a medicinal plant species containing many
      polyphenolic compounds, namely flavonoids and phenolic acids. In this study we
      evaluate the effect of Hypericum perforatum in animal model of periodontitis.
      METHODS: Periodontitis was induced in adult male Sprague-Dawley rats by placing a
      nylon thread ligature around the lower 1st molars. Hypericum perforatum was
      administered at the dose of 2 mg/kg os, daily for eight days. At day 8, the
      gingivomucosal tissue encircling the mandibular first molar was removed. RESULTS:
      Periodontitis in rats resulted in an inflammatory process characterized by edema,
      neutrophil infiltration and cytokine production that was followed by the
      recruitment of other inflammatory cells, production of a range of inflammatory
      mediators such as NF-kappaB and iNOS expression, the nitration of tyrosine
      residues and activation of the nuclear enzyme poly (ADP-ribose) polymerase;
      apoptosis and the degree of gingivomucosal tissues injury. We report here that
      Hypericum perforatum exerts potent anti-inflammatory effects significantly
      reducing all of the parameters of inflammation as described above. CONCLUSIONS:
      Taken together, our results clearly demonstrate that treatment with Hypericum
      reduces the development of inflammation and tissue injury, events associated with
      periodontitis.

PMID- 21092264
TI  - Delirium epidemiology in critical care (DECCA): an international study.
AB  - INTRODUCTION: Delirium is a frequent source of morbidity in intensive care units
      (ICUs). Most data on its epidemiology is from single-center studies. Our aim was
      to conduct a multicenter study to evaluate the epidemiology of delirium in the
      ICU. METHODS: A 1-day point-prevalence study was undertaken in 104 ICUs from 11
      countries in South and North America and Spain. RESULTS: In total, 975 patients
      were screened, and 497 fulfilled inclusion criteria and were enrolled (median
      age, 62 years; 52.5% men; 16.7% and 19.9% for ICU and hospital mortality); 64%
      were admitted to the ICU because of medical causes, and sepsis was the main
      diagnosis (n = 76; 15.3%). In total, 265 patients were sedated with the Richmond
      agitation and sedation scale (RASS) deeper than -3, and only 232 (46.6%) patients
      could be evaluated with the confusion-assessment method for the ICU. The
      prevalence of delirium was 32.3%. Compared with patients without delirium, those
      with the diagnosis of delirium had a greater severity of illness at admission,
      demonstrated by higher sequential organ-failure assessment (SOFA (P = 0.004)) and
      simplified acute physiology score 3 (SAPS3) scores (P < 0.0001). Delirium was
      associated with increased ICU (20% versus 5.7%; P = 0.002) and hospital mortality
      (24 versus 8.3%; P = 0.0017), and longer ICU (P < 0.0001) and hospital length of
      stay (LOS) (22 (11 to 40) versus 7 (4 to 18) days; P < 0.0001). Previous use of
      midazolam (P = 0.009) was more frequent in patients with delirium. On
      multivariate analysis, delirium was independently associated with increased ICU
      mortality (OR = 3.14 (1.26 to 7.86); CI, 95%) and hospital mortality (OR = 2.5
      (1.1 to 5.7); CI, 95%). CONCLUSIONS: In this 1-day international study, delirium
      was frequent and associated with increased mortality and ICU LOS. The main
      modifiable risk factors associated with the diagnosis of delirium were the use of
      invasive devices and sedatives (midazolam).

PMID- 21092265
TI  - Expression, regulation and function of phosphofructo-kinase/fructose
      biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute
      lymphoblastic leukemia cells.
AB  - BACKGROUND: Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in
      lymphoid cells and constitute a central component in the therapy of lymphoid
      malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2
      (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling
      glucose metabolism, was identified by us previously as a GC response gene in
      expression profiling analyses performed in children with ALL during initial
      systemic GC mono-therapy. Since deregulation of glucose metabolism has been
      implicated in apoptosis induction, this gene and its relatives, PFKFB1, 3, and 4,
      were further analyzed. METHODS: Gene expression analyses of isolated lymphoblasts
      were performed on Affymetrix HGU133 Plus 2.0 microarrays. GCRMA normalized
      microarray data were analyzed using R-Bioconductor packages version 2.5.
      Functional gene analyses of PFKFB2-15A and -15B isoforms were performed by
      conditional gene over-expression experiments in the GC-sensitive T-ALL model CCRF
      CEM. RESULTS: Expression analyses in additional ALL children, non-leukemic
      individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in
      most systems sensitive to GC-induced apoptosis, particularly T-ALL cells. The 3
      other family members, in contrast, were either absent or only weakly expressed
      (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression
      in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (PFKFB2
      15A and PFKFB2-15B) had no detectable effect on cell survival. Moreover, neither
      PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC
      induced apoptosis. CONCLUSIONS: Our data suggest that, at least in the model
      system investigated, PFKFB2 is not an essential upstream regulator of the anti
      leukemic effects of GC.

PMID- 21092266
TI  - Bullying in school and cyberspace: Associations with depressive symptoms in Swiss
      and Australian adolescents.
AB  - BACKGROUND: Cyber-bullying (i.e., bullying via electronic means) has emerged as a
      new form of bullying that presents unique challenges to those victimised. Recent
      studies have demonstrated that there is a significant conceptual and practical
      overlap between both types of bullying such that most young people who are cyber
      bullied also tend to be bullied by more traditional methods. Despite the overlap
      between traditional and cyber forms of bullying, it remains unclear if being a
      victim of cyber-bullying has the same negative consequences as being a victim of
      traditional bullying. METHOD: The current study investigated associations between
      cyber versus traditional bullying and depressive symptoms in 374 and 1320
      students from Switzerland and Australia respectively (52% female; Age: M = 13.8,
      SD = 1.0). All participants completed a bullying questionnaire (assessing
      perpetration and victimisation of traditional and cyber forms of bullying
      behaviour) in addition to scales on depressive symptoms. RESULTS: Across both
      samples, traditional victims and bully-victims reported more depressive symptoms
      than bullies and non-involved children. Importantly, victims of cyber-bullying
      reported significantly higher levels of depressive symptoms, even when
      controlling for the involvement in traditional bullying/victimisation.
      CONCLUSIONS: Overall, cyber-victimisation emerged as an additional risk factor
      for depressive symptoms in adolescents involved in bullying.

PMID- 21092267
TI  - Social desirability and self-reported health risk behaviors in web-based
      research: three longitudinal studies.
AB  - BACKGROUND: These studies sought to investigate the relation between social
      desirability and self-reported health risk behaviors (e.g., alcohol use, drug
      use, smoking) in web-based research. METHODS: Three longitudinal studies (Study
      1: N = 5612, 51% women; Study 2: N = 619, 60%; Study 3: N = 846, 59%) among
      randomly selected members of two online panels (Dutch; German) using several
      social desirability measures (Marlowe-Crowne Scale; Balanced Inventory of
      Desirable Responding; The Social Desirability Scale-17) were conducted. RESULTS:
      Social desirability was not associated with self-reported current behavior or
      behavior frequency. Socio-demographics (age; sex; education) did not moderate the
      effect of social desirability on self-reported measures regarding health risk
      behaviors. CONCLUSIONS: The studies at hand provided no convincing evidence to
      throw doubt on the usefulness of the Internet as a medium to collect self-reports
      on health risk behaviors.

PMID- 21092268
TI  - Probabilistic principal component analysis for metabolomic data.
AB  - BACKGROUND: Data from metabolomic studies are typically complex and high
      dimensional. Principal component analysis (PCA) is currently the most widely used
      statistical technique for analyzing metabolomic data. However, PCA is limited by
      the fact that it is not based on a statistical model. RESULTS: Here,
      probabilistic principal component analysis (PPCA) which addresses some of the
      limitations of PCA, is reviewed and extended. A novel extension of PPCA, called
      probabilistic principal component and covariates analysis (PPCCA), is introduced
      which provides a flexible approach to jointly model metabolomic data and
      additional covariate information. The use of a mixture of PPCA models for
      discovering the number of inherent groups in metabolomic data is demonstrated.
      The jackknife technique is employed to construct confidence intervals for
      estimated model parameters throughout. The optimal number of principal components
      is determined through the use of the Bayesian Information Criterion model
      selection tool, which is modified to address the high dimensionality of the data.
      CONCLUSIONS: The methods presented are illustrated through an application to
      metabolomic data sets. Jointly modeling metabolomic data and covariates was
      successfully achieved and has the potential to provide deeper insight to the
      underlying data structure. Examination of confidence intervals for the model
      parameters, such as loadings, allows for principled and clear interpretation of
      the underlying data structure. A software package called MetabolAnalyze, freely
      available through the R statistical software, has been developed to facilitate
      implementation of the presented methods in the metabolomics field.

PMID- 21092269
TI  - Truth or fallacy? Three hour wait for three minutes with the doctor: Findings
      from a private clinic in rural Japan.
AB  - INTRODUCTION: While previous reports examine various aspects of Family Medicine
      in Japan, there is sparse research on consultation lengths. A common phrase
      permeates throughout Japan, sanjikan machi, sanpun shinsatsu that means, "Three
      hour wait, three minute visit." The purpose of this study is to examine
      consultation length in Japan, and how it is affected by patient variables. CASE
      DESCRIPTION: We conducted a case study of consultation length and how it varies
      in relation to the demographics, presenting illness, and diagnoses at a rural
      clinic in central Japan. Data were coded according to the standards of the
      International Classification of Primary Care. Descriptive statistics were
      obtained to identify features of the data. Further, regression analysis was
      performed to characterize and to quantify the association between length of
      consultation and various subject level characteristics. DISCUSSION AND
      EVALUATION: A total of 263 patients aged 0 - 93 years old had consultations
      during the 8-day study period. The mean consultation duration was 6.12 minutes.
      Of all consultations, 11.8% lasted 3 minutes or less. The mean (median)
      consultation time among males was 6.29 (5.2) minutes and among females was 6.03
      (5.4) minutes. The duration of visits increased with age. Among different
      International Classification of Primary Care categories, psychological issues
      required the most time (mean = 10.75 min, median = 10.9 min) while urological
      issues required the least (mean = 5.08 min, median = 4.9 min). The majority of
      cases seen in the clinic were stable, chronic conditions and required shorter
      consultation times. CONCLUSIONS: While the mean and median consultation length in
      this study extends beyond the anecdotal three minutes, the average length of
      consultation is still remarkably short. Trends affecting consultation length were
      similar to other international studies. These data present only one aspect of
      primary care delivery in Japan. To better understand the significance of
      consultation length relative to the delivery of primary care, future research
      should examine issues such as continuity, frequency of consultations over time
      and comprehensiveness of care.

PMID- 21092270
TI  - Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced
      model of asthma: a randomized laboratory study.
AB  - BACKGROUND: Antigen desensitization through oral tolerance is becoming an
      increasingly attractive treatment option for allergic diseases. However, the
      mechanism(s) by which tolerization is achieved remain poorly defined. In this
      study we endeavored to induce oral tolerance to cockroach allergen (CRA: a
      complex mixture of insect components) in order to ameliorate asthma-like,
      allergic pulmonary inflammation. METHODS: We compared the pulmonary inflammation
      of mice which had received four CRA feedings prior to intratracheal allergen
      sensitization and challenge to mice fed PBS on the same time course. Respiratory
      parameters were assessed by whole body unrestrained plethysmography and
      mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid
      (BAL) and lung homogenate (LH) were assessed for cytokines and chemokines by
      ELISA. BAL inflammatory cells were also collected and examined by light
      microscopy. RESULTS: CRA feeding prior to allergen sensitization and challenge
      led to a significant improvement in respiratory health. Airways hyperreactivity
      measured indirectly via enhanced pause (Penh) was meaningfully reduced in the CRA
      fed mice compared to the PBS fed mice (2.3 +/- 0.4 vs 3.9 +/- 0.6; p = 0.03).
      Directly measured airways resistance confirmed this trend when comparing the CRA
      fed to the PBS-fed animals (2.97 +/- 0.98 vs 4.95 +/- 1.41). This effect was not
      due to reduced traditional inflammatory cell chemotactic factors, Th2 or other
      cytokines and chemokines. The mechanism of improved respiratory health in the
      tolerized mice was due to significantly reduced eosinophil numbers in the
      bronchoalveolar lavage fluid (43300 +/- 11445 vs 158786 +/- 38908; p = 0.007) and
      eosinophil specific peroxidase activity in the lung homogenate (0.59 +/- 0.13 vs
      1.19 +/- 0.19; p = 0.017). The decreased eosinophilia was likely the result of
      increased IL-10 in the lung homogenate of the tolerized mice (6320 +/- 354 ng/mL
      vs 5190 +/- 404 ng/mL, p = 0.02). CONCLUSION: Our results show that oral
      tolerization to CRA can improve the respiratory health of experimental mice in a
      CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary
      eosinophilia.

PMID- 21092271
TI  - Reversed halo sign in pneumocystis pneumonia: a case report.
AB  - BACKGROUND: The reversed halo sign may sometimes be seen in patients with
      cryptogenic organizing pneumonia, but is rarely associated with other diseases.
      CASE PRESENTATION: We present a case study of a 32-year-old male patient with
      acquired immunodeficiency syndrome, who had previously been treated with
      chemotherapy for non-Hodgkin's lymphoma. A chest X-ray showed bilateral patchy
      infiltrates. High-resolution computed tomography revealed the reversed halo sign
      in both upper lobes. The patient was diagnosed with pneumocystis pneumonia, which
      was successfully treated with sulfamethoxazole trimethoprim; the reversed halo
      sign disappeared, leaving cystic lesions. Cases such as this one are rare, but
      show that the reversed halo sign may occur in patients who do not have
      cryptogenic organizing pneumonia. CONCLUSION: Physicians can avoid making an
      incorrect diagnosis and prescribing the wrong treatment by carefully evaluating
      all clinical criteria rather than assuming that the reversed halo sign only
      occurs with cryptogenic organizing pneumonia.

PMID- 21092272
TI  - Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in
      an intact pig model.
AB  - INTRODUCTION: We developed a minimally invasive, closed chest pig model with the
      main aim to describe hemodynamic function during surface cooling, steady state
      severe hypothermia (one hour at 25 degrees C) and surface rewarming. METHODS:
      Twelve anesthetized juvenile pigs were acutely catheterized for measurement of
      left ventricular (LV) pressure-volume loops (conductance catheter), cardiac
      output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were
      surface cooled to 25 degrees C, while four animals were kept as normothermic time
      matched controls. RESULTS: During progressive cooling and steady state severe
      hypothermia (25 degrees C) cardiac output (CO), stroke volume (SV), mean arterial
      pressure (MAP), maximal deceleration of pressure in the cardiac cycle
      (dP/dt(min)), indexes of LV contractility (preload recruitable stroke work, PRSW,
      and maximal acceleration of pressure in the cardiac cycle, dP/dt(max)) and LV end
      diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic
      vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen
      content in arterial and mixed venous blood increased significantly. LV end
      diastolic pressure (EDP) remained constant. After rewarming all the above
      mentioned hemodynamic variables that were depressed during 25 degrees C remained
      reduced, except for CO that returned to pre-hypothermic values due to an increase
      in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming,
      while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac
      troponin T (TnT) and tumor necrosis factor-alpha (TNF-alpha) were significantly
      increased. CONCLUSIONS: Progressive cooling to 25 degrees C followed by rewarming
      resulted in a reduced systolic, but not diastolic left ventricular function. The
      post-hypothermic increase in heart rate and the reduced systemic vascular
      resistance are interpreted as adaptive measures by the organism to compensate for
      a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic
      increase in TnT indicates that hypothermia/rewarming may cause degradation of
      cardiac tissue. There were no signs of inadequate global oxygenation throughout
      the experiments.

PMID- 21092273
TI  - Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP)-targeted delivery of
      soluble TRAIL potently inhibits melanoma outgrowth in vitro and in vivo.
AB  - BACKGROUND: Advanced melanoma is characterized by a pronounced resistance to
      therapy leading to a limited patient survival of ~6 - 9 months. Here, we report
      on a novel bifunctional therapeutic fusion protein, designated anti-MCSP:TRAIL,
      that is comprised of a melanoma-associated chondroitin sulfate proteoglycan
      (MCSP)-specific antibody fragment (scFv) fused to soluble human TRAIL. MCSP is a
      well-established target for melanoma immunotherapy and has recently been shown to
      provide important tumorigenic signals to melanoma cells. TRAIL is a highly
      promising tumoricidal cytokine with no or minimal toxicity towards normal cells.
      Anti-MCSP:TRAIL was designed to 1. selectively accrete at the cell surface of
      MCSP-positive melanoma cells and inhibit MCSP tumorigenic signaling and 2.
      activate apoptotic TRAIL-signaling. RESULTS: Treatment of a panel of MCSP
      positive melanoma cell lines with anti-MCSP:TRAIL induced TRAIL-mediated
      apoptotic cell death within 16 h. Of note, treatment with anti-MCSP:sTRAIL was
      also characterized by a rapid dephosphorylation of key proteins, such as FAK,
      implicated in MCSP-mediated malignant behavior. Importantly, anti-MCSP:TRAIL
      treatment already inhibited anchorage-independent growth by 50% at low picomolar
      concentrations, whereas > 100 fold higher concentrations of non-targeted TRAIL
      failed to reduce colony formation. Daily i.v. treatment with a low dose of anti
      MCSP:TRAIL (0.14 mg/kg) resulted in a significant growth retardation of
      established A375 M xenografts. Anti-MCSP:TRAIL activity was further synergized by
      co-treatment with rimcazole, a sigma-ligand currently in clinical trials for the
      treatment of various cancers. CONCLUSIONS: Anti-MCSP:TRAIL has promising pre
      clinical anti-melanoma activity that appears to result from combined inhibition
      of tumorigenic MCSP-signaling and concordant activation of TRAIL-apoptotic
      signaling. Anti-MCSP:TRAIL alone, or in combination with rimcazole, may be of
      potential value for the treatment of malignant melanoma.

PMID- 21092275
TI  - Stages of use: consideration, initiation, utilization, and outcomes of an
      internet-mediated intervention.
AB  - BACKGROUND: Attrition, or nonuse of the intervention, is a significant problem in
      e-health. However, the reasons for this phenomenon are poorly understood.
      Building on Eysenbach's "Law of Attrition", this study aimed to explore the usage
      behavior of users of e-health services. We used two theoretical models,
      Andersen's Behavioral Model of Health Service Utilization and Venkatesh's Unified
      Theory of Acceptance and Use of Technology, to explore the factors associated
      with uptake and use of an internet-mediated intervention for caregivers taking
      care of a family member with dementia. METHODS: A multiphase, longitudinal design
      was used to follow a convenience sample of 46 family caregivers who received an e
      health intervention. Applying the two theories, usage behavior was conceptualized
      to form four stages: consideration, initiation, utilization (attrition or
      continuation), and outcome. The variables and measurement scales were selected
      based on these theories to measure the sociodemographic context, technology
      aptitudes, and clinical needs of the caregivers. RESULTS: In the Consideration
      Stage, caregivers who felt that the information communication technology (ICT)
      mediated service was easy to use were more likely to consider participating in
      the study (p = 0.04). In the Initiation Stage, caregivers who showed greater
      technology acceptance were more likely to initiate service earlier (p = 0.02). In
      the Utilization Stage, the frequent users were those who had a more positive
      attitude toward technology (p = 0.04) and a lower perceived caregiver competence
      (p = 0.04) compared with nonusers. In the Outcome Stage, frequent users
      experienced a decline in perceived burden compared with an escalation of
      perceived burden by nonusers (p = 0.02). CONCLUSIONS: We illustrate a
      methodological framework describing how to develop and expand a theory on
      attrition. The proposed framework highlighted the importance of conceptualizing e
      health "use" and "adoption" as dynamic, continuous, longitudinal processes
      occurring in different stages, influenced by different factors to predict
      advancement to the next stage. Although usage behavior was influenced mainly by
      technological factors in the initial stages, both clinical and technological
      factors were equally important in the later stages. Frequency of use was
      associated with positive clinical outcomes. A plausible explanation was that
      intervention benefits motivated the caregivers to continue the service and
      regular use led to more positive clinical outcome.

PMID- 21092274
TI  - Targeted gene delivery in tumor xenografts by the combination of ultrasound
      targeted microbubble destruction and polyethylenimine to inhibit survivin gene
      expression and induce apoptosis.
AB  - BACKGROUND: Noninvasive and tissue-specific technologies of gene transfection
      would be valuable in clinical gene therapy. This present study was designed to
      determine whether it could enhance gene transfection in vivo by the combination
      of ultrasound-targeted microbubble destruction (UTMD) with polyethylenimine (PEI)
      in tumor xenografts, and illuminate the effects of gene silencing and apoptosis
      induction with short hairpin RNA (shRNA) interference therapy targeting human
      survivin by this novel technique. METHODS: Two different expression vectors (pCMV
      LUC and pSIREN) were incubated with PEI to prepare cationic complexes (PEI/DNA)
      and confirmed by the gel retardation assay. Human cervical carcinoma (Hela)
      tumors were planted subcutaneously in both flanks of nude mice. Tumor-bearing
      mice were administered by tail vein with PBS, plasmid, plasmid and SonoVue
      microbubble, PEI/DNA and SonoVue microbubble. One tumor was exposed to ultrasound
      irradiation, while the other served as control. The feasibility of targeted
      delivery and tissue specificity facilitated by UTMD and PEI were investigated.
      Moreover, immunohistochemistry analyses about gene silencing and apoptosis
      induction were detected. RESULTS: Electrophoresis experiment revealed that PEI
      could condense DNA efficiently. The application of UTMD significantly increases
      the tissue transfection. Both expression vectors showed that gene expressions
      were present in all sections of tumors that received ultrasound exposure but not
      in control tumors. More importantly, the increases in transgene expression were
      related to UTMD with the presence of PEI significantly. Silencing of the survivin
      gene could induce apoptosis effectively by downregulating survivin and bcl-2
      expression, also cause up-regulation of bax and caspase-3 expression.
      CONCLUSIONS: This noninvasive, novel combination of UTMD with PEI could enhance
      targeted gene delivery and gene expression in tumor xenografts at intravenous
      administration effectively without causing any apparently adverse effect, and
      might be a promising candidate for gene therapy. Silencing of survivin gene
      expression with shRNA could be facilitated by this non-viral technique, and lead
      to significant cell apoptosis.

PMID- 21092278
TI  - Increased levels of circulating Annexin A5 in Familial Mediterranean fever.
AB  - BACKGROUND: Familial Mediterranean fever is a genetic autoinflammatory disease
      most commonly affecting the ethnic groups originating from around the
      Mediterranean Sea. Apoptosis plays an important role in down-regulation of the
      inflammatory response by reducing the lifespan of activated immunocompetent
      cells. Thus, increased apoptosis may be associated with pathogenesis of familial
      Mediterranean fever. METHODS: In the present study we determined the serum levels
      of apoptotic marker, Annexin A5, in familial Mediterranean fever patients, within
      an attack and attack-free, in comparison to healthy subjects and assessed the
      influence of colchicine treatment on this parameter. In addition, in all study
      subjects serum levels of C-reactive protein and interleukine-1beta, and the total
      leukocyte count were also determined. RESULTS: Our results demonstrated that
      pathogenesis of familial Mediterranean fever is characterized by the increased
      levels of circulating Annexin A5, which is higher in patients within the attack
      and which associate with the increased levels of C-reactive protein and
      interleukine-1beta and total leukocyte count. CONCLUSIONS: The results obtained
      indicate elevated rates of apoptosis of subpopulations of leukocytes involved in
      autoinflammation and recurrent episodes of fever in familial Mediterranean fever.
      It was also revealed that regular colchicine treatment sufficiently decreases the
      rate of apoptosis in familial Mediterranean fever patients by affecting the
      intensity of autoinflammatory reactions.

PMID- 21092277
TI  - TGF-beta-induced growth inhibition in B-cell lymphoma correlates with Smad1/5
      signalling and constitutively active p38 MAPK.
AB  - BACKGROUND: Cytokines of the transforming growth factor beta (TGF-beta)
      superfamily exert effects on proliferation, apoptosis and differentiation in
      various cell types. Cancer cells frequently acquire resistance to the anti
      proliferative signals of TGF-beta, which can be due to mutations in proteins of
      the signalling cascade. We compared the TGF-beta-related signalling properties in
      B-cell lymphoma cell lines that were sensitive or resistant to TGF-beta-induced
      anti-proliferative effects. RESULTS: TGF-beta sensitive cell lines expressed
      higher cell surface levels of the activin receptor-like kinase 5 (Alk-5), a TGF
      beta receptor type 1. The expression levels of the other TGF-beta and bone
      morphogenetic protein receptors were comparable in the different cell lines. TGF
      beta-induced phosphorylation of Smad2 was similar in TGF-beta sensitive and
      resistant cell lines. In contrast, activation of Smad1/5 was restricted to cells
      that were sensitive to growth inhibition by TGF-beta. Moreover, with activin A we
      detected limited anti-proliferative effects, strong phosphorylation of Smad2, but
      no Smad1/5 phosphorylation. Up-regulation of the TGF-beta target genes Id1 and
      Pai-1 was identified in the TGF-beta sensitive cell lines. Constitutive
      phosphorylation of MAPK p38 was restricted to the TGF-beta sensitive cell lines.
      Inhibition of p38 MAPK led to reduced sensitivity to TGF-beta. CONCLUSIONS: We
      suggest that phosphorylation of Smad1/5 is important for the anti-proliferative
      effects of TGF-beta in B-cell lymphoma. Alk-5 was highly expressed in the
      sensitive cell lines, and might be important for signalling through Smad1/5. Our
      results indicate a role for p38 MAPK in the regulation of TGF-beta-induced anti
      proliferative effects.

PMID- 21092276
TI  - Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of
      improved prognosis in breast cancer.
AB  - BACKGROUND: Conflicting data exist regarding the prognostic and predictive impact
      of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic
      to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer.
      Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we
      present new data suggesting that a low CNR may predict outcome in tamoxifen
      treated patients. METHODS: Survin expression was assessed using
      immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512
      tumours. Whole slide digital images were captured using an Aperio XT scanner.
      Automated image analysis was used to identify tumour from stroma and then to
      quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model
      selected using a 10-fold cross-validation approach was used to identify
      prognostic subgroups based on nuclear and cytoplasmic survivin expression.
      RESULTS: Following optimisation of the staining procedure, it was possible to
      evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours
      represented on the TMA. Decision tree analysis predicted that nuclear, as opposed
      to cytoplasmic, survivin was the most important determinant of overall survival
      (OS) and breast cancer-specific survival (BCSS). The decision tree model
      confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate
      analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS
      (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR
      (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008).
      An increased CNR was associated with ER positive (p = 0.045), low grade (p =
      0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high
      CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients
      (HR 0.44, 95% CI 0.23-0.87, p = 0.018). CONCLUSION: Using the same threshold as
      our previous study, we have validated survivin CNR as a marker of good prognosis
      in breast cancer in a large independent cohort. These findings provide robust
      evidence of the importance of survivin CNR as a breast cancer biomarker, and its
      potential to predict outcome in tamoxifen-treated patients.

PMID- 21092279
TI  - Evaluation of FTIR spectroscopy as a diagnostic tool for lung cancer using
      sputum.
AB  - BACKGROUND: Survival time for lung cancer is poor with over 90% of patients dying
      within five years of diagnosis primarily due to detection at late stage. The main
      objective of this study was to evaluate Fourier transform infrared spectroscopy
      (FTIR) as a high throughput and cost effective method for identifying biochemical
      changes in sputum as biomarkers for detection of lung cancer. METHODS: Sputum was
      collected from 25 lung cancer patients in the Medlung observational study and 25
      healthy controls. FTIR spectra were generated from sputum cell pellets using
      infrared wavenumbers within the 1800 to 950 cm-1 "fingerprint" region. RESULTS: A
      panel of 92 infrared wavenumbers had absorbances significantly different between
      cancer and normal sputum spectra and were associated with putative changes in
      protein, nucleic acid and glycogen levels in tumours. Five prominent significant
      wavenumbers at 964 cm-1, 1024 cm-1, 1411 cm-1, 1577 cm-1 and 1656 cm-1 separated
      cancer spectra from normal spectra into two distinct groups using multivariate
      analysis (group 1: 100% cancer cases; group 2: 92% normal cases). Principal
      components analysis revealed that these wavenumbers were also able to distinguish
      lung cancer patients who had previously been diagnosed with breast cancer. No
      patterns of spectra groupings were associated with inflammation or other diseases
      of the airways. CONCLUSIONS: Our results suggest that FTIR applied to sputum
      might have high sensitivity and specificity in diagnosing lung cancer with
      potential as a non-invasive, cost-effective and high-throughput method for
      screening. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00899262.

PMID- 21092280
TI  - Decrease of vitamin D concentration in patients with HIV infection on a non
      nucleoside reverse transcriptase inhibitor-containing regimen.
AB  - BACKGROUND: Vitamin D is an important determinant of bone health and also plays a
      major role in the regulation of the immune system. Interestingly, vitamin D
      status before the start of highly active antiretroviral therapy (HAART) has been
      recently associated with HIV disease progression and overall mortality in HIV
      positive pregnant women. We prospectively studied vitamin D status in HIV
      individuals on HAART in Belgium.We selected samples from HIV-positive adults
      starting HAART with a pre-HAART CD4 T-cell count >100 cells/mm3 followed up for
      at least 12 months without a treatment change. We compared 25-hydroxyvitamin D
      plasma [25-(OH)D] concentration in paired samples before and after 12 months of
      HAART. 25-(OH)D levels are presented using two different cut-offs: <20 ng/ml and
      <30 ng/ml. RESULTS: Vitamin D deficiency was common before HAART, the frequency
      of plasma 25-(OH)D concentrations below 20 ng/ml and 30 below ng/ml was 43.7% and
      70.1% respectively. After 12 months on HAART, the frequency increased to 47.1%
      and 81.6%.HAART for 12 months was associated with a significant decrease of
      plasma 25-(OH)D concentration (p = 0.001). Decreasing plasma 25-(OH)D
      concentration on HAART was associated in the multivariate model with NNRTI-based
      regimen (p = 0.001) and lower body weight (p = 0.008). Plasma 25-(OH)D
      concentrations decreased significantly in both nevirapine and efavirenz
      containing regimens but not in PI-treated patients. CONCLUSIONS: Vitamin D
      deficiency is frequent in HIV-positive individuals and NNRTI therapy further
      decreases 25-(OH)D concentrations. Consequently, vitamin D status need to be
      checked regularly in all HIV-infected patients and vitamin D supplementation
      should be given when needed.

PMID- 21092281
TI  - HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2
      interactions and delays cell cycle progression.
AB  - BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) has efficiently adapted
      to its host and establishes a persistent infection characterized by low levels of
      viral gene expression and slow proliferation of HTLV-I infected cells over
      decades. We have previously found that HTLV-I p30 is a negative regulator of
      virus expression. RESULTS: In this study we show that p30 targets multiple cell
      cycle checkpoints resulting in a delayed entry into S phase. We found that p30
      binds to cyclin E and CDK2 and prevents the formation of active cyclin E-CDK2
      complexes. In turn, this decreases the phosphorylation levels of Rb and prevents
      the release of E2F and its transcriptional activation of genes required for G1/S
      transition. Our studies also show that HTLV-II p28 does not bind cyclin E and
      does not affect cell cycle progression. CONCLUSIONS: In contrast to HTLV-I, the
      HTLV-II-related retrovirus is not oncogenic in humans. Here we report that the
      HTLV-I p30 delays cell cycle progression while its homologue, HTLV-II p28, does
      not, providing evidence for important differences between these two related
      retrovirus proteins.

PMID- 21092282
TI  - Identification of the 3' and 5' terminal sequences of the 8 rna genome segments
      of European and North American genotypes of infectious salmon anemia virus (an
      orthomyxovirus) and evidence for quasispecies based on the non-coding sequences
      of transcripts.
AB  - BACKGROUND: Infectious salmon anemia (ISA) virus (ISAV) is a pathogen of marine
      farmed Atlantic salmon (Salmo salar); a disease first diagnosed in Norway in
      1984. This virus, which was first characterized following its isolation in cell
      culture in 1995, belongs to the family Orthomyxoviridae, genus, Isavirus. The
      Isavirus genome consists of eight single-stranded RNA segments of negative sense,
      each with one to three open reading frames flanked by 3' and 5' non-coding
      regions (NCRs). Although the terminal sequences of other members of the family
      Orthomyxoviridae such as Influenzavirus A have been extensively analyzed, those
      of Isavirus remain largely unknown, and the few reported are from different ISAV
      strains and on different ends of the different RNA segments. This paper describes
      a comprehensive analysis of the 3' and 5' end sequences of the eight RNA segments
      of ISAV of both European and North American genotypes, and evidence of
      quasispecies of ISAV based on sequence variation in the untranslated regions
      (UTRs) of transcripts. RESULTS: Two different ISAV strains and two different RNA
      preparations were used in this study. ISAV strain ADL-PM 3205 ISAV-07 (ADL-ISAV
      07) of European genotype was the source of total RNA extracted from ISAV-infected
      TO cells, which contained both viral mRNA and cRNA. ISAV strain NBISA01 of North
      American genotype was the source of vRNA extracted from purified virus. The NCRs
      of each segment were identified by sequencing cDNA prepared by three different
      methods, 5' RACE (Rapid amplification of cDNA ends), 3' RACE, and RNA ligation
      mediated PCR. Sequence analysis of five clones each derived from one RT-PCR
      product from each NCR of ISAV transcripts of segments 1 to 8 revealed significant
      heterogeneity among the clones of the same segment end, providing unequivocal
      evidence for presence of intra-segment ISAV quasispecies. Both RNA preparations
      (mRNA/cRNA and vRNA) yielded complementary sequence information, allowing the
      simultaneous identification and confirmation of the 3' and 5' NCR sequences of
      the 8 RNA genome segments of both genotypes of ISAV. The 3' sequences of the mRNA
      transcripts of ADL-ISAV-07 terminated 13-18 nucleotides from the full 3' terminus
      of cRNA, continuing as a poly(A) tail, which corresponded with the location of
      the polyadenylation signal. The lengths of the 3' and 5' NCRs of the vRNA were
      variable in the different genome segments, but the terminal 7 and 11 nucleotides
      of the 3' and 5' ends, respectively, were highly conserved among the eight
      genomic segments of ISAV. The first three nucleotides at the 3' end are GCU-3'
      (except in segment 5 with ACU-3'), whereas at the 5' end are 5'-AGU with the
      polyadenylation signal of 3-5 uridines 13-15 nucleotides downstream of the 5' end
      terminus of the vRNA. Exactly the same features were found in the respective
      complementary 5' and 3' end NCR sequences of the cRNA transcripts of ADL-ISAV-07,
      indicating that the terminal sequences of the 8 RNA genome segments are highly
      conserved among the two ISAV genotypes. The 5' NCR sequences of segments 1, 2, 3,
      5, and 7, and the 3' NCR sequences of segments 3 and 4 cRNA were 100% identical
      in the two genotypes, and the 3' NCR sequences of segment 5 cRNA was the most
      divergent, with a sequence identity of 77.2%. CONCLUSIONS: We report for the
      first time, the presence of intra-segment ISAV quasispecies, based on sequence
      variation in the NCR sequences of transcripts. In addition, this is the first
      report of a comprehensive unambiguous analysis of the 3' and 5' NCR sequences of
      all 8 RNA genome segments from two strains of ISAV representing the two genotypes
      of ISAV. Because most ISAV sequences are of cDNA to mRNA, they do not contain the
      3' end sequences, which are removed during polyadenylation of the mRNA
      transcripts. We report for the first time the ISAV consensus sequence
      CAT/ATTTTTACT-3' (in the message sense 5'-3') in all segments of both ISAV
      genotypes.

PMID- 21092283
TI  - Using knowledge brokers to facilitate the uptake of pediatric measurement tools
      into clinical practice: a before-after intervention study.
AB  - BACKGROUND: The use of measurement tools is an essential part of good evidence
      based practice; however, physiotherapists (PTs) are not always confident when
      selecting, administering, and interpreting these tools. The purpose of this study
      was to evaluate the impact of a multifaceted knowledge translation intervention,
      using PTs as knowledge brokers (KBs) to facilitate the use in clinical practice
      of four evidence-based measurement tools designed to evaluate and understand
      motor function in children with cerebral palsy (CP). The KB model evaluated in
      this study was designed to overcome many of the barriers to research transfer
      identified in the literature. METHODS: A mixed methods before-after study design
      was used to evaluate the impact of a six-month KB intervention by 25 KBs on 122
      practicing PTs' self-reported knowledge and use of the measurement tools in 28
      children's rehabilitation organizations in two regions of Canada. The model was
      that of PT KBs situated in clinical sites supported by a network of KBs and the
      research team through a broker to the KBs. Modest financial remuneration to the
      organizations for the KB time (two hours/week for six months), ongoing resource
      materials, and personal and intranet support was provided to the KBs. Survey data
      were collected by questionnaire prior to, immediately following the intervention
      (six months), and at 12 and 18 months. A mixed effects multinomial logistic
      regression was used to examine the impact of the intervention over time and by
      region. The impact of organizational factors was also explored. RESULTS: PTs'
      self-reported knowledge of all four measurement tools increased significantly
      over the six-month intervention, and reported use of three of the four
      measurement tools also increased. Changes were sustained 12 months later.
      Organizational culture for research and supervisor expectations were
      significantly associated with uptake of only one of the four measurement tools.
      CONCLUSIONS: KBs positively influenced PTs' self-reported knowledge and self
      reported use of the targeted measurement tools. Further research is warranted to
      investigate whether this is a feasible, cost-effective model that could be used
      more broadly in a rehabilitation setting to facilitate the uptake of other
      measurement tools or evidence-based intervention approaches.

PMID- 21092284
TI  - Pash 3.0: A versatile software package for read mapping and integrative analysis
      of genomic and epigenomic variation using massively parallel DNA sequencing.
AB  - BACKGROUND: Massively parallel sequencing readouts of epigenomic assays are
      enabling integrative genome-wide analyses of genomic and epigenomic variation.
      Pash 3.0 performs sequence comparison and read mapping and can be employed as a
      module within diverse configurable analysis pipelines, including ChIP-Seq and
      methylome mapping by whole-genome bisulfite sequencing. RESULTS: Pash 3.0
      generally matches the accuracy and speed of niche programs for fast mapping of
      short reads, and exceeds their performance on longer reads generated by a new
      generation of massively parallel sequencing technologies. By exploiting longer
      read lengths, Pash 3.0 maps reads onto the large fraction of genomic DNA that
      contains repetitive elements and polymorphic sites, including indel
      polymorphisms. CONCLUSIONS: We demonstrate the versatility of Pash 3.0 by
      analyzing the interaction between CpG methylation, CpG SNPs, and imprinting based
      on publicly available whole-genome shotgun bisulfite sequencing data. Pash 3.0
      makes use of gapped k-mer alignment, a non-seed based comparison method, which is
      implemented using multi-positional hash tables. This allows Pash 3.0 to run on
      diverse hardware platforms, including individual computers with standard RAM
      capacity, multi-core hardware architectures and large clusters.

PMID- 21092285
TI  - Dissection of an old protein reveals a novel application: domain D of
      Staphylococcus aureus Protein A (sSpAD) as a secretion--tag.
AB  - BACKGROUND: Escherichia coli as a frequently utilized host organism for
      recombinant protein production offers different cellular locations with distinct
      qualities. The periplasmic space is often favored for the production of complex
      proteins due to enhanced disulfide bond formation, increased target product
      stability and simplified downstream processing. To direct proteins to the
      periplasmic space rather small proteinaceus tags that can be used for affinity
      purification would be advantageous. RESULTS: We discovered that domain D of the
      Staphylococcus aureus protein A was sufficient for the secretion of various
      target proteins into the periplasmic space of E. coli. Our experiments indicated
      the Sec pathway as the mode of secretion, although N-terminal processing was not
      observed. Furthermore, the solubility of recombinant fusion proteins was improved
      for proteins prone to aggregation.The tag allowed a straightforward affinity
      purification of recombinant fusion protein via an IgG column, which was
      exemplified for the target protein human superoxide dismutase 1 (SOD).
      CONCLUSIONS: In this work we present a new secretion tag that combines several
      advantages for the production of recombinant proteins in E. coli. Domain D of S.
      aureus protein A protects the protein of interest against N-terminal degradation,
      increases target protein solubility and enables a straight-forward purification
      of the recombinant protein using of IgG columns.

PMID- 21092286
TI  - Transcriptome analysis of a barley breeding program examines gene expression
      diversity and reveals target genes for malting quality improvement.
AB  - BACKGROUND: Advanced cycle breeding utilizes crosses among elite lines and is a
      successful method to develop new inbreds. However, it results in a reduction in
      genetic diversity within the breeding population. The development of malting
      barley varieties requires the adherence to a narrow malting quality profile and
      thus the use of advanced cycle breeding strategies. Although attention has been
      focused on diversity in gene expression and its association with genetic
      diversity, there are no studies performed in a single breeding program examining
      the implications that consecutive cycles of breeding have on gene expression
      variation and identifying the variability still available for future improvement.
      RESULTS: Fifteen lines representing the historically important six-rowed malting
      barley breeding program of the University of Minnesota were genotyped with 1,524
      SNPs, phenotypically examined for six malting quality traits, and analyzed for
      transcript accumulation during germination using the Barley1 GeneChip array.
      Significant correlation was detected between genetic and transcript-level
      variation. We observed a reduction in both genetic and gene expression diversity
      through the breeding process, although the expression of many genes have not been
      fixed. A high number of quality-related genes whose expression was fixed during
      the breeding process was identified, indicating that much of the diversity
      reduction was associated with the improvement of the complex phenotype "malting
      quality", the main goal of the University of Minnesota breeding program. We also
      identified 49 differentially expressed genes between the most recent lines of the
      program that were correlated with one or more of the six primary malting quality
      traits. These genes constitute potential targets for the improvement of malting
      quality within the breeding program. CONCLUSIONS: The present study shows the
      repercussion of advanced cycle breeding on gene expression diversity within an
      important barley breeding program. A reduction in gene expression diversity was
      detected, although there is diversity still present after forty years of breeding
      that can exploited for future crop improvement. In addition, the identification
      of candidate genes for enhancing malting quality may be used to optimize the
      selection of targets for further improvements in this economically important
      phenotype.

PMID- 21092287
TI  - Pharmacokinetic and pharmacodynamic comparison of two "pegylated" interferon
      alpha-2 formulations in healthy male volunteers: a randomized, crossover, double
      blind study.
AB  - BACKGROUND: Interferon (IFN) alpha conjugation to polyethylene glycol (PEG)
      results in a better pharmacokinetic profile and efficacy. The aim of this study
      was to compare the pharmacokinetic, pharmacodynamic and safety properties of a
      new, locally developed, 40-kDa PEG-IFN alpha-2b preparation with a reference,
      commercially available PEG-IFN alpha-2a in healthy male volunteers. METHODS: A
      randomized, crossover, double-blind study with a 3-weeks washout period, was
      done. A single 180 micrograms PEG-IFN alpha-2 dose was administered
      subcutaneously in both groups. Sixteen apparently healthy male subjects were
      included. Serum PEG-IFN concentration was measured during 336 hours by an enzyme
      immunoassay (EIA). Other clinical and laboratory variables were used as
      pharmacodynamic and safety criteria. RESULTS: The pharmacokinetic comparison by
      EIA yielded a high similitude between the formulations. In spite of a high
      subject variability, the parameters' mean were very close (in all cases p >
      0.05): AUC: 53623 vs. 44311 pg.h/mL; Cmax: 333 vs. 271 pg/mL; Tmax: 54 vs. 55 h;
      half-life (t1/2): 72.4 vs. 64.8 h; terminal elimination rate (lambda): 0.011 vs.
      0.014 h(-1); mean residence time (MRT): 135 vs. 123 h for reference and study
      preparations, respectively. There were no significant differences with respect to
      the pharmacodynamic variables either: serum neopterin and beta-2 microglobulin
      levels, stimulation of 2'5' oligoadenylate synthetase expression, and serum IFN
      antiviral activity. A strong Spearman's rank order correlation (p < 0.01) between
      the pharmacokinetic and pharmacodynamic concentration-time curves was observed.
      Both products caused similar leukocyte counts diminution and had similar safety
      profiles. The most frequent adverse reactions were leukopenia, fever,
      thrombocytopenia, transaminases increase and asthenia, mostly mild. CONCLUSIONS:
      Both formulations are fully comparable from the pharmacokinetic, pharmacodynamic,
      and safety profiles. Efficacy trials can be carried out to confirm clinical
      similarity.

PMID- 21092288
TI  - Hypofractionated radiotherapy after conservative surgery for breast cancer:
      analysis of acute and late toxicity.
AB  - BACKGROUND: A variety of hypofractionated radiotherapy schedules has been
      proposed after breast conserving surgery in the attempt to shorten the overall
      treatment time. The aim of the present study is to assess acute and late toxicity
      of using daily fractionation of 2.25 Gy to a total dose of 45 Gy to the whole
      breast in a mono-institutional series. METHODS: Eighty-five women with early
      breast cancer were assigned to receive 45 Gy followed by a boost to the tumour
      bed. Early and late toxicity were scored according to the Radiation Therapy
      Oncology Group criteria. For comparison, a group of 70 patients with similar
      characteristics and treated with conventional fractionation of 2 Gy to a total
      dose of 50 Gy in 25 fractions followed by a boost, was retrospectively selected.
      RESULTS: Overall median treatment duration was 29 days for hypofractionated
      radiotherapy and 37 days for conventional radiotherapy. Early reactions were
      observed in 72/85 (85%) patients treated with hypofractionation and in 67/70
      (96%) patients treated with conventional fractionation (p = 0.01). Late toxicity
      was observed in 8 patients (10%) in the hypofractionation group and in 10
      patients (15%) in the conventional fractionation group, respectively (p = 0.4).
      CONCLUSIONS: The hypofractionated schedule delivering 45 Gy in 20 fractions
      shortened the overall treatment time by 1 week with a reduction of skin acute
      toxicity and no increase of late effects compared to the conventional
      fractionation. Our results support the implementation of hypofractionated
      schedules in clinical practice.

PMID- 21092289
TI  - Fed-batch fermentation of GM-CSF-producing glycoengineered Pichia pastoris under
      controlled specific growth rate.
AB  - BACKGROUND: Yeast expression systems with altered N-glycosylation are now
      available to produce glycoproteins with homogenous, defined N-glycans. However,
      data on the behaviour of these strains in high cell density cultivation are
      scarce. RESULTS: Here, we report on cultivations under controlled specific growth
      rate of a GlycoSwitch-Man5 Pichia pastoris strain producing Granulocyte
      Macrophage Colony-Stimulating Factor (GM-CSF) at high levels (hundreds of
      milligrams per liter). We demonstrate that homogenous Man5GlcNAc2 N-glycosylation
      of the secreted proteins is achieved at all specific growth rates tested.
      CONCLUSIONS: Together, these data illustrate that the GlycoSwitch-Man5 P.
      pastoris is a robust production strain for homogenously N-glycosylated proteins.

PMID- 21092290
TI  - Cross-comparison of cardiac output trending accuracy of LiDCO, PiCCO, FloTrac and
      pulmonary artery catheters.
AB  - INTRODUCTION: Although less invasive than pulmonary artery catheters (PACs),
      arterial pulse pressure analysis techniques for estimating cardiac output (CO)
      have not been simultaneously compared to PAC bolus thermodilution CO (COtd) or
      continuous CO (CCO) devices. METHODS: We compared the accuracy, bias and trending
      ability of LiDCOTM, PiCCOTM and FloTracTM with PACs (COtd, CCO) to simultaneously
      track CO in a prospective observational study in 17 postoperative cardiac surgery
      patients for the first 4 hours following intensive care unit admission. Fifty
      five paired simultaneous quadruple CO measurements were made before and after
      therapeutic interventions (volume, vasopressor/dilator, and inotrope). RESULTS:
      Mean CO values for PAC, LiDCO, PiCCO and FloTrac were similar (5.6 +/- 1.5, 5.4
      +/- 1.6, 5.4 +/- 1.5 and 6.1 +/- 1.9 L/min, respectively). The mean CO bias by
      each paired method was -0.18 (PAC-LiDCO), 0.24 (PAC-PiCCO), -0.43 (PAC-FloTrac),
      0.06 (LiDCO-PiCCO), -0.63 (LiDCO-FloTrac) and -0.67 L/min (PiCCO-FloTrac), with
      limits of agreement (1.96 standard deviation, 95% confidence interval) of +/-
      1.56, +/- 2.22, +/- 3.37, +/- 2.03, +/- 2.97 and +/- 3.44 L/min, respectively.
      The instantaneous directional changes between any paired CO measurements
      displayed 74% (PAC-LiDCO), 72% (PAC-PiCCO), 59% (PAC-FloTrac), 70% (LiDCO-PiCCO),
      71% (LiDCO-FloTrac) and 63% (PiCCO-FloTrac) concordance, but poor correlation
      (r(2) = 0.36, 0.11, 0.08, 0.20, 0.23 and 0.11, respectively). For mean CO < 5
      L/min measured by each paired devices, the bias decreased slightly. CONCLUSIONS:
      Although PAC (COTD/CCO), FloTrac, LiDCO and PiCCO display similar mean CO values,
      they often trend differently in response to therapy and show different
      interdevice agreement. In the clinically relevant low CO range (< 5 L/min),
      agreement improved slightly. Thus, utility and validation studies using only one
      CO device may potentially not be extrapolated to equivalency of using another
      similar device.

PMID- 21092291
TI  - DeltaProt: a software toolbox for comparative genomics.
AB  - BACKGROUND: Statistical bioinformatics is the study of biological data sets
      obtained by new micro-technologies by means of proper statistical methods. For a
      better understanding of environmental adaptations of proteins, orthologous
      sequences from different habitats may be explored and compared. The main goal of
      the DeltaProt Toolbox is to provide users with important functionality that is
      needed for comparative screening and studies of extremophile proteins and protein
      classes. Visualization of the data sets is also the focus of this article, since
      visualizations can play a key role in making the various relationships
      transparent. This application paper is intended to inform the reader of the
      existence, functionality, and applicability of the toolbox. RESULTS: We present
      the DeltaProt Toolbox, a software toolbox that may be useful in importing,
      analyzing and visualizing data from multiple alignments of proteins. The toolbox
      has been written in MATLABTM to provide an easy and user-friendly platform,
      including a graphical user interface, while ensuring good numerical performance.
      Problems in genome biology may be easily stated thanks to a compact input format.
      The toolbox also offers the possibility of utilizing structural information from
      the SABLE or other structure predictors. Different sequence plots can then be
      viewed and compared in order to find their similarities and differences. Detailed
      statistics are also calculated during the procedure. CONCLUSIONS: The DeltaProt
      package is open source and freely available for academic, non-commercial use. The
      latest version of DeltaProt can be obtained from
      http://services.cbu.uib.no/software/deltaprot/. The website also contains
      documentation, and the toolbox comes with real data sets that are intended for
      training in applying the models to carry out bioinformatical and statistical
      analyses of protein sequences.Equipped with the new algorithms proposed here,
      DeltaProt serves as an auxiliary analysis tool capable of visualizing and
      comparing orthologus protein sequences. The framework of the algorithms also
      enables easy incorporation of extra information on structure, if such data is
      available.

PMID- 21092292
TI  - Dishevelled-3 C-terminal His single amino acid repeats are obligate for Wnt5a
      activation of non-canonical signaling.
AB  - BACKGROUND: The Wnt non-canonical pathway (Wnt5a > Frizzled-2 > cyclic GMP
      phosphodiesterase/Ca2+-mobilization pathway regulates the activation of NF-AT) is
      mediated by three mammalian Dishevelleds (Dvl1, Dvl2, and Dvl3) and the role of
      the C-terminal region unique to Dvl3 was interrogated. RESULTS: Dvl1, Dvl2, and
      Dvl3 are expressed at varying levels in mouse totipotent F9 embryonal
      teratocarcinoma cells. The expression of each endogenous Dvl isoform, as defined
      by knock-down with siRNA, was obligate for Wnt5a to activate NF-AT-sensitive
      transcription. Elements upstream of effectors, e.g., cGMP phosphodiesterase and
      Ca2+-mobilization, were blocked by knock-down of any one of the Dvls; thus, with
      respect to Wnt5a activation of NF-AT Dvls are not redundant. Among the three Dvl
      isoforms, the C-terminal sequence of Dvl3 is the most divergent. Deletion of
      region of Dvl3 abolishes Wnt5a-stimulated signaling. Alanine (Ala)-substitution
      of histidine (His) single amino acid repeats at 637,638 and/or 647,648 in Dvl3,
      like C-terminal deletion, abolishes Wnt 5a signal propagation. Phenylalanine
      (Phe)-substitution of the same His-repeats in Dvl3 mimics Wnt5a stimulated NF-AT
      sensitive transcription. CONCLUSIONS: The C-terminal third of Dvl3 and His single
      amino acid repeats 637,638 and 647,648 (which are unique to and conserved in
      Dvl3) are essential for Wnt5a activation of the non-canonical pathway, but not
      the Wnt3a activation of the canonical pathway.

PMID- 21092293
TI  - The optimization of the diagnostic work-up in patients with suspected obstructive
      lung disease.
AB  - BACKGROUND: Pulmonary function testing is a key procedure in the work-up of
      patients who are suspected of having asthma and chronic obstructive lung disease
      (COPD). Therein, clinical visits and pulmonary function tests (PFTs) are the
      major contributors to the overall financial costs.The aim of this study was to
      assess whether a specific diagnostic test protocol contributes to the
      optimization of the work-up of patients who are suspected of having asthma and
      COPD. METHODS: A prospective, single-blind, and randomized controlled study was
      performed. In the control group (CG), all of the PFTs that were ordered by the
      lung specialist were carried out. In the experimental group (EG), specific PFTs
      were selected according to our protocol. The primary end point was the total cost
      of achieving a final diagnosis. RESULTS: One hundred and seventy-nine patients
      were included into this study: 86 in the CG and 93 in the EG. The mean number of
      tests to diagnosis was 3.8 in the CG versus 2.9 in the EG (P < 0.001). The mean
      number of redundant PFTs before diagnosis was 1.2 in the CG versus 0.08 in the EG
      (P < 0.001). The number of patients who required an additional outpatient visit
      to complete diagnosis was higher in the CG in comparison to the EG (P = 0.02).
      The mean cost of work-up per diagnosis was ?227 in the CG versus ?181 in the EG
      (P < 0.001). CONCLUSIONS: In this group of patients with suspected obstructive
      lung disease, protocol-driven, PFT-based selection is more cost-effective than
      test selection at the discretion of lung physicians.

PMID- 21092294
TI  - Investigation of DNA damage response and apoptotic gene methylation pattern in
      sporadic breast tumors using high throughput quantitative DNA methylation
      analysis technology.
AB  - BACKGROUND: Sporadic breast cancer like many other cancers is proposed to be a
      manifestation of abnormal genetic and epigenetic changes. For the past decade our
      laboratory has identified genes involved in DNA damage response (DDR), apoptosis
      and immunosurveillance pathways to influence sporadic breast cancer risk in north
      Indian population. Further to enhance our knowledge at the epigenetic level, we
      performed DNA methylation study involving 17 gene promoter regions belonging to
      DNA damage response (DDR) and death receptor apoptotic pathway in 162 paired
      normal and cancerous breast tissues from 81 sporadic breast cancer patients,
      using a high throughput quantitative DNA methylation analysis technology.
      RESULTS: The study identified five genes with statistically significant
      difference between normal and tumor tissues. Hypermethylation of DR5 (P=0.001),
      DCR1 (P=0.00001), DCR2 (P=0.0000000005) and BRCA2 (P=0.007) and hypomethylation
      of DR4 (P=0.011) in sporadic breast tumor tissues suggested a weak/aberrant
      activation of the DDR/apoptotic pathway in breast tumorigenesis. Negative
      correlation was observed between methylation status and transcript expression
      levels for TRAIL, DR4, CASP8, ATM, CHEK2, BRCA1 and BRCA2 CpG sites.
      Categorization of the gene methylation with respect to the clinicopathological
      parameters showed an increase in aberrant methylation pattern in advanced tumors.
      These uncharacteristic methylation patterns corresponded with decreased death
      receptor apoptosis (P=0.047) and DNA damage repair potential (P=0.004) in
      advanced tumors. The observation of BRCA2 -26 G/A 5'UTR polymorphism concomitant
      with the presence of methylation in the promoter region was novel and emerged as
      a strong candidate for susceptibility to sporadic breast tumors. CONCLUSION: Our
      study indicates that methylation of DDR-apoptotic gene promoters in sporadic
      breast cancer is not a random phenomenon. Progressive epigenetic alterations in
      advancing tumors result in aberrant DDR-apoptotic pathway thereby promoting tumor
      development. We propose, since pathological epigenetic changes of the DDR
      apoptotic genes are reversible modifications, these could further be targeted for
      therapeutic interventions.

PMID- 21092295
TI  - Three-dimension structure of ventricular myocardial fibers after myocardial
      infarction.
AB  - BACKGROUND: To explore the pathological changes of three-dimension structure of
      ventricular myocardial fibers after anterior myocardial infarction in dog heart.
      METHODS: Fourteen acute anterior myocardial infarction models were made from
      healthy dogs (mean weight 17.6 +/- 2.5 kg). Six out of 14 dogs with old
      myocardial infarction were sacrificed, and their hearts were harvested after they
      survived the acute anterior myocardial infarction for 3 months. Each heart was
      dissected into ventricular myocardial band (VMB), morphological characters in
      infarction region were observed, and infarct size percents in descending segment
      and ascending segment were calculated. RESULTS: Six dog hearts were successfully
      dissected into VMB. Uncorresponding damages in myocardial fibers of descending
      segment and ascending segment were found in apical circle in anterior wall
      infarction. Infarct size percent in the ascending segment was significantly
      larger than that in the descending segment (23.36 +/- 3.15 (SD) vs 30.69 +/-
      2.40%, P = 0.0033); the long axis of infarction area was perpendicular to the
      orientation of myocardial fibers in ascending segment; however, the long axis of
      the infarction area was parallel with the orientation of myocardial fibers in
      descending segment. CONCLUSIONS: We found that damages were different in both
      morphology and size in ascending segment and descending segment in heart with
      myocardial infarction. This may provide an important insight for us to understand
      the mechanism of heart failure following coronary artery diseases.

PMID- 21092296
TI  - Biomedical engineering meets acupuncture--development of a miniaturized 48
      channel skin impedance measurement system for needle and laser acupuncture.
AB  - BACKGROUND: Due to controversially discussed results in scientific literature
      concerning changes of electrical skin impedance before and during acupuncture a
      new measurement system has been developed. METHODS: The prototype measures and
      analyzes the electrical skin impedance computer-based and simultaneously in 48
      channels within a 2.5*3.5 cm matrix. Preliminary measurements in one person were
      performed using metal needle and violet laser (405 nm) acupuncture at the
      acupoint Kongzui (LU6). The new system is an improvement on devices previously
      developed by other researchers for this purpose. RESULTS: Skin impedance in the
      immediate surroundings of the acupoint was lowered reproducibly following needle
      stimulation and also violet laser stimulation. CONCLUSIONS: A new instrumentation
      for skin impedance measurements is presented. The following hypotheses suggested
      by our results will have to be tested in further studies: Needle acupuncture
      causes significant, specific local changes of electrical skin impedance
      parameters. Optical stimulation (violet laser) at an acupoint causes direct
      electrical biosignal changes.

PMID- 21092297
TI  - 3D-CT implanted interstitial brachytherapy for T2b nasopharyngeal carcinoma.
AB  - BACKGROUND: To compare the results of external beam radiotherapy in combination
      with 3D- computed tomography (CT)-implanted interstitial high dose rate
      brachytherapy (ERT/3D-HDR-BT) versus conventional external beam radiotherapy
      (ERT) for the treatment of stage T2b nasopharyngeal carcinoma (NPC). METHODS:
      Forty NPC patients diagnosed with stage T2b NPC were treated with ERT/3D-HDR-BT
      under local anesthesia. These patients received a mean dose of 60 Gy, followed by
      12-20 Gy administered by 3D-HDR-BT. Another 101 patients diagnosed with non
      metastatic T2b NPC received a mean dose of 68 Gy by ERT alone during the same
      period. RESULTS: Patients treated with ERT/3D-HDR-BT versus ERT alone exhibited
      an improvement in their 5-y local failure-free survival rate (97.5% vs. 80.2%, P
      = 0.012) and disease-free survival rate (92.5% vs. 73.3%, P = 0.014). Using
      multivariate analysis, administration of 3D-HDR-BT was found to be favorable for
      local control (P = 0.046) and was statistically significant for disease-free
      survival (P = 0.021). The incidence rate of acute and chronic complications
      between the two groups was also compared. CONCLUSIONS: It is possible that the
      treatment modality enhances local control due to improved conformal dose
      distributions and the escalated radiation dose applied.

PMID- 21092298
TI  - Minimization of free radical damage by metal catalysis of
      multivitamin/multimineral supplements.
AB  - Multivitamin/multimineral complexes are the most common dietary supplements.
      Unlike minerals in foods that are incorporated in bioorganic structures, minerals
      in dietary supplements are typically in an inorganic form. These minerals can
      catalyze the generation of free radicals, thereby oxidizing antioxidants during
      digestion. Here we examine the ability of a matrix consisting of an amino acid
      and non-digestible oligosaccharide (AAOS) to blunt metal-catalyzed oxidations.
      Monitoring of ascorbate radical generated by copper shows that ascorbate is
      oxidized more slowly with the AAOS matrix than with copper sulfate. Measurement
      of the rate of oxidation of ascorbic acid and Trolox(r) by catalytic metals
      confirmed the ability of AAOS to slow these oxidations. Similar results were
      observed with iron-catalyzed formation of hydroxyl radicals. When compared to
      traditional forms of minerals used in supplements, we conclude that the oxidative
      loss of antioxidants in solution at physiological pH is much slower when AAOS is
      present.

PMID- 21092299
TI  - Patient-oriented gene set analysis for cancer mutation data.
AB  - Recent research has revealed complex heterogeneous genomic landscapes in human
      cancers. However, mutations tend to occur within a core group of pathways and
      biological processes that can be grouped into gene sets. To better understand the
      significance of these pathways, we have developed an approach that initially
      scores each gene set at the patient rather than the gene level. In mutation
      analysis, these patient-oriented methods are more transparent, interpretable, and
      statistically powerful than traditional gene-oriented methods.

PMID- 21092300
TI  - The provision of non-needle/syringe drug injecting paraphernalia in the primary
      prevention of HCV among IDU: a systematic review.
AB  - BACKGROUND: Sharing drug injecting paraphernalia other than needles and syringes
      (N/S) has been implicated in the transmission of Hepatitis C virus (HCV) among
      injecting drug users (IDU). We aimed to determine whether the provision of
      sterile non-N/S injecting paraphernalia reduces injecting risk behaviours or HCV
      transmission among IDU. METHODS: A systematic search of seven databases and the
      grey literature for articles published January 1989-February 2010 was undertaken.
      Thirteen studies (twelve observational and one non-randomized uncontrolled pilot
      intervention) were identified and appraised for study design and quality by two
      investigators. RESULTS: No studies examined the association between the provision
      of non-N/S injecting paraphernalia and incident HCV infection. One cross
      sectional study found that individuals who frequently, compared to those who
      infrequently, used sterile cookers and water, were less likely to report
      prevalent HCV infection. Another found no association between the uptake of
      sterile non-N/S injecting paraphernalia and self-reported sharing of this
      paraphernalia. The remaining observational studies used attendance at needle and
      syringe exchange programmes (NSP) or safer injection facilities (SIF) that
      provided non-N/S injecting paraphernalia as a proxy measure. Eight studies
      presented adjusted odds ratios, ranging from 0.3 to 0.9, suggesting a reduced
      likelihood of self-reported sharing of non-N/S injecting paraphernalia associated
      with use of NSP or SIF. There was substantial uncertainty associated with these
      estimates however. Three unadjusted studies reported a reduction in the
      prevalence of sharing of non-N/S injecting paraphernalia over time among NSP
      users. Only one study reported an adjusted temporal trend in the prevalence of
      sharing non-N/S injecting paraphernalia, finding higher rates among non-NSP users
      than NSP users at each time point, and a greater reduction in sharing among non
      NSP than NSP users over time. Study limitations included the use of convenience
      samples, self-reported exposure and outcome measures, flawed classification of
      the exposed and unexposed groups, and inadequate adjustment for potential
      confounding variables. CONCLUSIONS: The evidence to demonstrate that the
      provision of sterile non-N/S injecting paraphernalia reduces HCV transmission or
      modifies injecting risk behaviours is currently limited by an insufficient volume
      and quality of studies. Further research is required to inform practice and
      policy in this area.

PMID- 21092301
TI  - Treatment and disease progression in a birth cohort of vertically HIV-1 infected
      children in Ukraine.
AB  - BACKGROUND: Ukraine has the highest HIV prevalence (1.6%) and is facing the
      fastest growing epidemic in Europe. Our objective was to describe the clinical,
      immunological and virological characteristics, treatment and response in
      vertically HIV-infected children living in Ukraine and followed from birth.
      METHODS: The European Collaborative Study (ECS) is an ongoing cohort study, in
      which HIV-1 infected pregnant women are enrolled and followed in pregnancy, and
      their children prospectively followed from birth. ECS enrolment in Ukraine
      started in 2000 initially with three sites, increasing to seven sites by 2009.
      RESULTS: A total of 245 infected children were included in the cohort by April
      2009, with a median age of 23 months at most recent follow-up; 33% (n = 77) had
      injecting drug using mothers and 85% (n = 209) were infected despite some use of
      antiretroviral prophylaxis for prevention of mother-to-child transmission. Fifty
      five (22%) children had developed AIDS, at a median age of 10 months (IQR = 6
      19). The most prevalent AIDS indicator disease was Pneumocystis jiroveci
      pneumonia (PCP). Twenty-seven (11%) children had died (median age, 6.2 months).
      Overall, 108 (44%) children had started highly active antiretroviral treatment
      (HAART), at a median 18 months of age; median HAART duration was 6.6 months to
      date. No child discontinued HAART and 92% (100/108) remained on their first-line
      HAART regimen to date. Among children with moderate/severe immunosuppression, 36%
      had not yet started HAART. Among children on HAART, 71% (69/97) had no evidence
      of immunosuppression at their most recent visit; the median reduction in HIV RNA
      was 4.69 log10 copies/mL over a median of 10 months treatment. From survival
      analysis, an estimated 94%, 84% and 81% of children will be alive and AIDS-free
      at 6, 12 and 18 months of age, respectively. However, survival increased
      significantly over time: estimated survival rates to 12 months of age were 87%
      for children born in 2000/03 versus 96% for those born in 2004/08. CONCLUSION:
      One in five children had AIDS and one in ten had died. The half of children who
      received HAART has responded well and survival has significantly improved over
      time. Earlier diagnosis and prompt initiation of HAART remain key challenges.

PMID- 21092302
TI  - Constitutive emission of the aphid alarm pheromone, (E)-beta-farnesene, from
      plants does not serve as a direct defense against aphids.
AB  - BACKGROUND: The sesquiterpene, (E)-beta-farnesene (EBF), is the principal
      component of the alarm pheromone of many aphid species. Released when aphids are
      attacked by enemies, EBF leads aphids to undertake predator avoidance behaviors
      and to produce more winged offspring that can leave the plant. Many plants also
      release EBF as a volatile, and so it has been proposed that this compound could
      act to defend plants against aphid infestation by 1) deterring aphids from
      settling, 2) reducing aphid performance due to frequent interruption of feeding
      and 3) inducing the production of more winged offspring. Here we tested the costs
      and benefits of EBF as a defense against the green peach aphid, Myzus persicae,
      using transgenic Arabidopsis thaliana lines engineered to continuously emit EBF.
      RESULTS: No metabolic costs of EBF synthesis could be detected in these plants as
      they showed no differences in growth or seed production from wild-type controls
      under two fertilizer regimes. Likewise, no evidence was found for the ability of
      EBF to directly defend the plant against aphids. EBF emission did not
      significantly repel winged or wingless morphs from settling on plants. Nor did
      EBF reduce aphid performance, measured as reproduction, or lead to an increase in
      the proportion of winged offspring. CONCLUSIONS: The lack of any defensive effect
      of EBF in this study might be due to the fact that natural enemy attack on
      individual aphids leads to a pulsed emission, but the transgenic lines tested
      continuously produce EBF to which aphids may become habituated. Thus our results
      provide no support for the hypothesis that plant emission of the aphid alarm
      pheromone EBF is a direct defense against aphids. However, there is scattered
      evidence elsewhere in the literature suggesting that EBF emission might serve as
      an indirect defense by attracting aphid predators.

PMID- 21092303
TI  - An exploration of the knowledge and attitudes towards breastfeeding among a
      sample of Chinese mothers in Ireland.
AB  - BACKGROUND: Psychological factors are important in influencing breastfeeding
      practices. This retrospective study explored knowledge and attitudes related to
      breastfeeding of Chinese mothers living in Ireland. METHODS: A cross-sectional
      self-administrated survey written in Chinese was distributed to a convenience
      sample of 322 immigrant Chinese mothers mainly via Chinese supermarkets and
      Chinese language schools in Dublin, with the involvement of the snowball method
      to increase sample size. Maternal breastfeeding knowledge and attitudes were
      described, their associations with socio-demographic variables were explored by
      Chi-square analysis, and their independent associations with breastfeeding
      behaviours were estimated by binary logistic regression analyses. RESULTS: In
      spite of considerable awareness of the advantages of breastfeeding (mean score =
      4.03 +/- 0.73), some misconceptions (e.g. 'mother should stop breastfeeding if
      she catches a cold') and negative attitudes (e.g. breastfeeding inconvenient,
      embarrassing, and adverse to mothers' figure) existed, especially among the less
      educated mothers. Cultural beliefs concerning the traditional Chinese postpartum
      diet were prevalent, particularly among those who had lived in Ireland for a
      shorter duration (P = 0.004). Psychological parameters had strong independent
      associations with breastfeeding practices in this study. Those who had lower
      awareness score (OR = 2.98, 95% CI: 1.87-4.73), more misconceptions and negative
      attitudes (P < 0.05), and weaker cultural beliefs (P < 0.05) were less likely to
      breastfeed. CONCLUSIONS: Findings highlight a need to focus resources and
      education on correcting the misconceptions identified and reversing the negative
      attitudes towards breastfeeding among Chinese mothers in Ireland, in particular
      those with primary/secondary level of education. Mothers' cultural beliefs should
      also be acknowledged and understood by healthcare providers.

PMID- 21092304
TI  - Effectiveness of psychotherapeutic, pharmacological, and combined treatments for
      chronic depression: a systematic review (METACHRON).
AB  - BACKGROUND: Chronic depressions represent a substantial part of depressive
      disorders and are associated with severe consequences. Several studies were
      performed addressing the effectiveness of psychotherapeutic, pharmacological, and
      combined treatments for chronic depressions. Yet, a systematic review comparing
      the effectiveness of multiple treatment options and considering all subtypes of
      chronic depressions is still missing. METHODS/DESIGN: Aim of this project is to
      summarize empirical evidence on efficacy and effectiveness of treatments for
      chronic depression by means of a systematic review. The primary objectives of the
      study are to examine, which interventions are effective; to examine, if any
      differences in effectiveness between active treatment options exist; and to find
      possible treatment effect modifiers. Psychotherapeutic, pharmacological, and
      combined treatments will be considered as experimental interventions and no
      treatment, wait-list, psychological/pharmacological placebo, treatment as usual,
      and other active treatments will be seen as comparators. The population of
      patients will include adults with chronic major depression, dysthymia, double
      depression, or recurrent depression without complete remission between episodes.
      Outcomes of the analyses are depressive symptoms, associated consequences,
      adverse events, and study discontinuation. Only randomized controlled trials will
      be considered. DISCUSSION: Given the high prevalence and serious consequences of
      chronic depression and a considerable amount of existing primary studies
      addressing the effectiveness of different treatments the present systematic
      review may be of high relevance. Special attention will be given to the use of
      current methodological standards. Findings are likely to provide crucial
      information that may help clinicians to choose the appropriate treatment for
      chronically depressed patients.

PMID- 21092305
TI  - Multiple mycobacterial antigens are targets of the adaptive immune response in
      pulmonary sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease for which the
      association with mycobacteria continues to strengthen. It is hypothesized that a
      single, poorly degradable antigen is responsible for sarcoidosis pathogenesis.
      Several reports from independent groups support mycobacterial antigens having a
      role in sarcoidosis pathogenesis. To identify other microbial targets of the
      adaptive immune response, we tested the ability of CD4+ and CD8+ T cells to
      recognize multiple mycobacterial antigens. METHODS: Fifty-four subjects were
      enrolled in this study: 31 sarcoidosis patients, nine non-tuberculosis
      mycobacterial (NTM) infection controls, and 14 PPD- controls. Using flow
      cytometry, we assessed for Th1 immune responses to ESAT-6, katG, Ag85A, sodA, and
      HSP. RESULTS: Alveolar T-cells from twenty-two of the 31 sarcoidosis patients
      produced a CD4+ response to at least one of ESAT-6, katG, Ag85A, sodA, or HSP,
      compared to two of 14 PPD- controls (p = 0.0008) and five of nine NTM controls (p
      = 0.44), while eighteen of the 31 sarcoidosis subjects tested produced a CD8+
      response to at least one of the mycobacterial antigens compared to two of 14 PPD-
      controls (p = 0.009) and three of nine NTM controls (0.26). Not only did the BAL
      derived T cells respond to multiple virulence factors, but also to multiple,
      distinct epitopes within a given protein. The detection of proliferation upon
      stimulation with the mycobacterial virulence factors demonstrates that these
      responses are initiated by antigen specific recognition. CONCLUSIONS: Together
      these results reveal that antigen-specific CD4+ and CD8+ T cells responses to
      multiple mycobacterial epitopes are present within sites of active sarcoidosis
      involvement, and that these antigen-specific responses are present at the time of
      diagnosis.

PMID- 21092306
TI  - Diversity of lactic acid bacteria of the bioethanol process.
AB  - BACKGROUND: Bacteria may compete with yeast for nutrients during bioethanol
      production process, potentially causing economic losses. This is the first study
      aiming at the quantification and identification of Lactic Acid Bacteria (LAB)
      present in the bioethanol industrial processes in different distilleries of
      Brazil. RESULTS: A total of 489 LAB isolates were obtained from four distilleries
      in 2007 and 2008. The abundance of LAB in the fermentation tanks varied between
      6.0 * 105 and 8.9 * 108 CFUs/mL. Crude sugar cane juice contained 7.4 * 107 to
      6.0 * 108 LAB CFUs. Most of the LAB isolates belonged to the genus Lactobacillus
      according to rRNA operon enzyme restriction profiles. A variety of Lactobacillus
      species occurred throughout the bioethanol process, but the most frequently found
      species towards the end of the harvest season were L. fermentum and L. vini. The
      different rep-PCR patterns indicate the co-occurrence of distinct populations of
      the species L. fermentum and L. vini, suggesting a great intraspecific diversity.
      Representative isolates of both species had the ability to grow in medium
      containing up to 10% ethanol, suggesting selection of ethanol tolerant bacteria
      throughout the process. CONCLUSIONS: This study served as a first survey of the
      LAB diversity in the bioethanol process in Brazil. The abundance and diversity of
      LAB suggest that they have a significant impact in the bioethanol process.

PMID- 21092307
TI  - Targeted therapy in lymphoma.
AB  - Discovery of new treatments for lymphoma that prolong survival and are less toxic
      than currently available agents represents an urgent unmet need. We now have a
      better understanding of the molecular pathogenesis of lymphoma, such as aberrant
      signal transduction pathways, which have led to the discovery and development of
      targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of
      rapamycin (mTOR) pathways are examples of pathological mechanisms that are being
      targeted in drug development efforts. Bortezomib (a small molecule protease
      inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus
      are some of the targeted therapies currently being studied in the treatment of
      aggressive, relapsed/refractory lymphoma. This review will discuss the rationale
      for and summarize the reported findings of initial and ongoing investigations of
      mTOR inhibitors and other small molecule targeted therapies in the treatment of
      lymphoma.

PMID- 21092308
TI  - Generation Scotland: Donor DNA Databank; A control DNA resource.
AB  - BACKGROUND: Many medical disorders of public health importance are complex
      diseases caused by multiple genetic, environmental and lifestyle factors. Recent
      technological advances have made it possible to analyse the genetic variants that
      predispose to complex diseases. Reliable detection of these variants requires
      genome-wide association studies in sufficiently large numbers of cases and
      controls. This approach is often hampered by difficulties in collecting
      appropriate control samples. The Generation Scotland: Donor DNA Databank (GS:3D)
      aims to help solve this problem by providing a resource of control DNA and plasma
      samples accessible for research. METHODS: GS:3D participants were recruited from
      volunteer blood donors attending Scottish National Blood Transfusion Service
      (SNBTS) clinics across Scotland. All participants gave full written consent for
      GS:3D to take spare blood from their normal donation. Participants also supplied
      demographic data by completing a short questionnaire. RESULTS: Over five thousand
      complete sets of samples, data and consent forms were collected. DNA and plasma
      were extracted and stored. The data and samples were unlinked from their original
      SNBTS identifier number. The plasma, DNA and demographic data are available for
      research. New data obtained from analysis of the resource will be fed back to
      GS:3D and will be made available to other researchers as appropriate.
      CONCLUSIONS: Recruitment of blood donors is an efficient and cost-effective way
      of collecting thousands of control samples. Because the collection is large,
      subsets of controls can be selected, based on age range, gender, and ethnic or
      geographic origin. The GS:3D resource should reduce time and expense for
      investigators who would otherwise have had to recruit their own controls.

PMID- 21092309
TI  - Health plan administrative records versus birth certificate records: quality of
      race and ethnicity information in children.
AB  - BACKGROUND: To understand racial and ethnic disparities in health care
      utilization and their potential underlying causes, valid information on race and
      ethnicity is necessary. However, the validity of pediatric race and ethnicity
      information in administrative records from large integrated health care systems
      using electronic medical records is largely unknown. METHODS: Information on race
      and ethnicity of 325,810 children born between 1998-2008 was extracted from
      health plan administrative records and compared to birth certificate records.
      Positive predictive values (PPV) were calculated for correct classification of
      race and ethnicity in administrative records compared to birth certificate
      records. RESULTS: Misclassification of ethnicity and race in administrative
      records occurred in 23.1% and 33.6% children, respectively; the majority due to
      missing ethnicity (48.3%) and race (40.9%) information. Misclassification was
      most common in children of minority groups. PPV for White, Black, Asian/Pacific
      Islander, American Indian/Alaskan Native, multiple and other was 89.3%, 86.6%,
      73.8%, 18.2%, 51.8% and 1.2%, respectively. PPV for Hispanic ethnicity was 95.6%.
      Racial and ethnic information improved with increasing number of medical visits.
      Subgroup analyses comparing racial classification between non-Hispanics and
      Hispanics showed White, Black and Asian race was more accurate among non
      Hispanics than Hispanics. CONCLUSIONS: In children, race and ethnicity
      information from administrative records has significant limitations in accurately
      identifying small minority groups. These results suggest that the quality of
      racial information obtained from administrative records may benefit from
      additional supplementation by birth certificate data.

PMID- 21092310
TI  - Comparative genomic analysis of Atlantic salmon, Salmo salar, from Europe and
      North America.
AB  - BACKGROUND: Several lines of evidence including allozyme analysis, restriction
      digest patterns and sequencing of mtDNA as well as mini- and micro-satellite
      allele frequencies indicate that Atlantic salmon (Salmo salar) from North America
      and Europe are genetically distinct. These observations are supported by
      karyotype analysis, which revealed that North American Atlantic salmon have 27
      pairs of chromosomes whereas European salmon have 29 pairs. We set out to
      construct a linkage map for a North American Atlantic salmon family and to
      compare this map with the well developed map for European Atlantic salmon.
      RESULTS: We used microsatellite markers, which had previously been mapped in the
      two Atlantic salmon SALMAP mapping families from the River Tay, Scotland, to
      carry out linkage analysis in an Atlantic salmon family (NB1) whose parents were
      derived from the Saint John River stock in New Brunswick, Canada. As large
      differences in recombination rates between female and male Atlantic salmon have
      been noted, separate genetic maps were constructed for each sex. The female
      linkage map comprises 218 markers in 37 linkage groups while the male map has 226
      markers in 28 linkage groups. We combined 280 markers from the female and male
      maps into 27 composite linkage groups, which correspond to the haploid number of
      chromosomes in Atlantic salmon from the Western Atlantic. CONCLUSIONS: A
      comparison of the composite NB1 and SALMAP linkage maps revealed the reason for
      the difference in the chromosome numbers between European and North American
      Atlantic salmon: Linkage groups AS-4 and AS-32 in the Scottish salmon, which
      correspond to chromosomes Ssa-6 and Ssa-22, are combined into a single NB1
      linkage group as are linkage groups AS-21 and AS-33 (corresponding to chromosomes
      Ssa-26 and Ssa-28). The comparison of the linkage maps also suggested some
      additional chromosomal rearrangements, but it will require finer mapping,
      potentially using SNPs, to test these predictions. Our results provide the first
      comparison of the genomic architecture of Atlantic salmon from North America and
      Europe with respect to chromosome organization.

PMID- 21092311
TI  - Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly
      effective in disrupting tumor angiogenesis.
AB  - BACKGROUND: Dll4/Notch and Ephrin-B2/EphB4 pathways play critical roles in tumor
      vessel development and maturation. This study evaluates the efficacy of the
      inhibition of both signaling pathways, alone and in combination, in reducing the
      growth of an autochthonous mouse tumor and assesses potential adverse effects.
      METHODS: We used the transgenic RIP1-Tag2 tumor model to study the effects of 1)
      inhibition of Dll4/Notch by either Dll4 allelic deletion or use of a soluble
      extracellular Dll4 (sDll4), 2) inhibition of Ephrin-B2/EphB4 signaling by a
      soluble extracellular EphB4 fused to albumin (sEphB4-Alb), and 3) inhibition of
      both pathways by sEphB4-Alb combined with either Dll4 allelic deletion or sDll4.
      To investigate adverse effects, we used inducible endothelial-specific Dll4 knock
      out mice, treated with sEphB4-Alb, and carried out histopathological analysis.
      RESULTS: Dll4 allele deletion or soluble Dll4 treatment resulted in increased
      tumor vessel density, reduced mural cell recruitment and vessel perfusion which
      resulted in reduced tumor size. The soluble EphB4 instead reduced vessel density
      and vessel perfusion, leading to reduction of tumor size. Greater efficacy was
      observed when sEphB4-Alb was combined with either Dll4 allele deletion or sDll4
      in regards to tumor size, vessel perfusion and mural cell recruitment. Induced
      endothelial specific Dll4 loss-of-function caused hepatic vascular alterations,
      which were prevented by concomitant sEphB4-Alb treatment. CONCLUSION: Combination
      targeting of Dll4/Notch and Ephrin-B2/EphB4 has potential for clinical
      investigation, providing cumulative efficacy and increased safety over Dll4/Notch
      inhibition alone.

PMID- 21092312
TI  - Development and analysis of an in vivo-compatible metabolic network of
      Mycobacterium tuberculosis.
AB  - BACKGROUND: During infection, Mycobacterium tuberculosis confronts a generally
      hostile and nutrient-poor in vivo host environment. Existing models and analyses
      of M. tuberculosis metabolic networks are able to reproduce experimentally
      measured cellular growth rates and identify genes required for growth in a range
      of different in vitro media. However, these models, under in vitro conditions, do
      not provide an adequate description of the metabolic processes required by the
      pathogen to infect and persist in a host. RESULTS: To better account for the
      metabolic activity of M. tuberculosis in the host environment, we developed a set
      of procedures to systematically modify an existing in vitro metabolic network by
      enhancing the agreement between calculated and in vivo-measured gene essentiality
      data. After our modifications, the new in vivo network contained 663 genes, 838
      metabolites, and 1,049 reactions and had a significantly increased sensitivity
      (0.81) in predicted gene essentiality than the in vitro network (0.31). We
      verified the modifications generated from the purely computational analysis
      through a review of the literature and found, for example, that, as the analysis
      suggested, lipids are used as the main source for carbon metabolism and oxygen
      must be available for the pathogen under in vivo conditions. Moreover, we used
      the developed in vivo network to predict the effects of double-gene deletions on
      M. tuberculosis growth in the host environment, explore metabolic adaptations to
      life in an acidic environment, highlight the importance of different enzymes in
      the tricarboxylic acid-cycle under different limiting nutrient conditions,
      investigate the effects of inhibiting multiple reactions, and look at the
      importance of both aerobic and anaerobic cellular respiration during infection.
      CONCLUSIONS: The network modifications we implemented suggest a distinctive set
      of metabolic conditions and requirements faced by M. tuberculosis during host
      infection compared with in vitro growth. Likewise, the double-gene deletion
      calculations highlight the importance of specific metabolic pathways used by the
      pathogen in the host environment. The newly constructed network provides a
      quantitative model to study the metabolism and associated drug targets of M.
      tuberculosis under in vivo conditions.

PMID- 21092313
TI  - Bovipain-2, the falcipain-2 ortholog, is expressed in intraerythrocytic stages of
      the tick-transmitted hemoparasite Babesia bovis.
AB  - BACKGROUND: Cysteine proteases have been shown to be highly relevant for
      Apicomplexan parasites. In the case of Babesia bovis, a tick-transmitted
      hemoparasite of cattle, inhibitors of these enzymes were shown to hamper
      intraerythrocytic replication of the parasite, underscoring their importance for
      survival. RESULTS: Four papain-like cysteine proteases were found to be encoded
      by the B. bovis genome using the MEROPS database. One of them, the ortholog of
      Plasmodium falciparum falcipain-2, here named bovipain-2, was further
      characterized. Bovipain-2 is encoded in B. bovis chromosome 4 by an ORF of 1.3
      kb, has a predicted molecular weight of 42 kDa, and is hydrophilic with the
      exception of a transmembrane region. It has orthologs in several other
      apicomplexans, and its predicted amino acid sequence shows a high degree of
      conservation among several B. bovis isolates from North and South America.
      Synteny studies demonstrated that the bovipain-2 gene has expanded in the genomes
      of two related piroplasmids, Theileria parva and T. annulata, into families of 6
      and 7 clustered genes respectively. The bovipain-2 gene is transcribed in in
      vitro cultured intra-erythrocyte forms of a virulent and an attenuated B. bovis
      strain from Argentina, and has no introns, as shown by RT-PCR followed by
      sequencing. Antibodies against a recombinant form of bovipain-2 recognized two
      parasite protein bands of 34 and 26 kDa, which coincide with the predicted sizes
      of the pro-peptidase and mature peptidase, respectively. Immunofluorescence
      studies showed an intracellular localization of bovipain-2 in the middle-rear
      region of in vitro cultured merozoites, as well as diffused in the cytoplasm of
      infected erythrocytes. Anti-bovipain-2 antibodies also reacted with B. bigemina
      infected erythrocytes giving a similar pattern, which suggests cross-reactivity
      among these species. Antibodies in sera of two out of six B. bovis-experimentally
      infected bovines tested, reacted specifically with recombinant bovipain-2 in
      immunoblots, thus demonstrating expression and immunogenicity during bovine
      infecting stages. CONCLUSIONS: Overall, we present the characterization of
      bovipain-2 and demonstrate its in vitro and in vivo expression in virulent and
      attenuated strains. Given the involvement of apicomplexan cysteine proteases in
      essential parasite functions, bovipain-2 constitutes a new vaccine candidate and
      potential drug target for bovine babesiosis.

PMID- 21092314
TI  - iGTP: a software package for large-scale gene tree parsimony analysis.
AB  - BACKGROUND: The ever-increasing wealth of genomic sequence information provides
      an unprecedented opportunity for large-scale phylogenetic analysis. However,
      species phylogeny inference is obfuscated by incongruence among gene trees due to
      evolutionary events such as gene duplication and loss, incomplete lineage sorting
      (deep coalescence), and horizontal gene transfer. Gene tree parsimony (GTP)
      addresses this issue by seeking a species tree that requires the minimum number
      of evolutionary events to reconcile a given set of incongruent gene trees.
      Despite its promise, the use of gene tree parsimony has been limited by the fact
      that existing software is either not fast enough to tackle large data sets or is
      restricted in the range of evolutionary events it can handle. RESULTS: We
      introduce iGTP, a platform-independent software program that implements state-of
      the-art algorithms that greatly speed up species tree inference under the
      duplication, duplication-loss, and deep coalescence reconciliation costs. iGTP
      significantly extends and improves the functionality and performance of existing
      gene tree parsimony software and offers advanced features such as building
      effective initial trees using stepwise leaf addition and the ability to have
      unrooted gene trees in the input. Moreover, iGTP provides a user-friendly
      graphical interface with integrated tree visualization software to facilitate
      analysis of the results. CONCLUSIONS: iGTP enables, for the first time, gene tree
      parsimony analyses of thousands of genes from hundreds of taxa using the
      duplication, duplication-loss, and deep coalescence reconciliation costs, all
      from within a convenient graphical user interface.

PMID- 21092315
TI  - Long descending cervical propriospinal neurons differ from thoracic propriospinal
      neurons in response to low thoracic spinal injury.
AB  - BACKGROUND: Propriospinal neurons, with axonal projections intrinsic to the
      spinal cord, have shown a greater regenerative response than supraspinal neurons
      after axotomy due to spinal cord injury (SCI). Our previous work focused on the
      response of axotomized short thoracic propriospinal (TPS) neurons following a low
      thoracic SCI (T9 spinal transection or moderate spinal contusion injury) in the
      rat. The present investigation analyzes the intrinsic response of cervical
      propriospinal neurons having long descending axons which project into the
      lumbosacral enlargement, long descending propriospinal tract (LDPT) axons. These
      neurons also were axotomized by T9 spinal injury in the same animals used in our
      previous study. RESULTS: Utilizing laser microdissection (LMD), qRT-PCR, and
      immunohistochemistry, we studied LDPT neurons (located in the C5-C6 spinal
      segments) between 3-days, and 1-month following a low thoracic (T9) spinal cord
      injury. We examined the response of 89 genes related to growth factors, cell
      surface receptors, apoptosis, axonal regeneration, and neuroprotection/cell
      survival. We found a strong and significant down-regulation of ~25% of the genes
      analyzed early after injury (3-days post-injury) with a sustained down-regulation
      in most instances. In the few genes that were up-regulated (Actb, Atf3, Frs2,
      Hspb1, Nrap, Stat1) post-axotomy, the expression for all but one was down
      regulated by 2-weeks post-injury. We also compared the uninjured TPS control
      neurons to the uninjured LDPT neurons used in this experiment for phenotypic
      differences between these two subpopulations of propriospinal neurons. We found
      significant differences in expression in 37 of the 84 genes examined between
      these two subpopulations of propriospinal neurons with LDPT neurons exhibiting a
      significantly higher base line expression for all but 3 of these genes compared
      to TPS neurons. CONCLUSIONS: Taken collectively these data indicate a broad
      overall down-regulation in the genes examined, including genes for
      neurotrophic/growth factor receptors as well as for several growth factors. There
      was a lack of a significant regenerative response, with the exception of an up
      regulation of Atf3 and early up-regulation of Hspb1 (Hsp27), both involved in
      cell stress/neuroprotection as well as axonal regeneration. There was no
      indication of a cell death response over the first month post-injury. In
      addition, there appear to be significant phenotypic differences between uninjured
      TPS and LDPT neurons, which may partly account for the differences observed in
      their post-axotomy responses. The findings in this current study stand in stark
      contrast to the findings from our previous work on TPS neurons. This suggests
      that different approaches will be needed to enhance the capacity for each
      population of propriospinal neuron to survive and undergo successful axonal
      regeneration after SCI.

PMID- 21092316
TI  - Process evaluation of a school based physical activity related injury prevention
      programme using the RE-AIM framework.
AB  - BACKGROUND: In general, only information regarding the effectiveness of an
      intervention programme is ever published. However, in recent years evaluating the
      translatability and feasibility of an intervention programme has become more
      important. Therefore, this paper presents the results of the evaluation of the
      iPlay programme aimed at preventing physical activity related injuries in primary
      school children. METHODS: The iPlay programme targeted injuries gained through
      physical activity, and consisted of a teacher's manual, informative newsletters
      and posters, a website, and set exercises to be carried out during physical
      education (PE) classes. In order to evaluate the iPlay programme for
      translatability and feasibility, teachers, children and parents who participated
      in the iPlay programme filled out a questionnaire. The objective of this study is
      to describe the results of the process-evaluation of the iPlay programme based on
      the five dimensions of the RE-AIM framework. RESULTS: The results showed that the
      participation rate of the children was 100% (reach). Nine percent of the schools
      who were invited to take part were willing to participate in the study (adoption
      rate). Teachers stated that they implemented the different elements of the
      programme partly as intended (implementation). The percentage of children and
      parents who followed the programme was less than expected. In addition, 52% of
      the teachers indicated that the current iPlay programme could become standard
      practice in their teaching routine (maintenance). CONCLUSION: The iPlay programme
      is a first start in the prevention of physical activity related injuries in
      children, but further improvements need to be made to the programme on the basis
      of this process evaluation. TRIAL REGISTRATION: ISRCTN78846684;
      http://www.controlled-trials.com.

PMID- 21092317
TI  - Sampling the conformation of protein surface residues for flexible protein
      docking.
AB  - BACKGROUND: The problem of determining the physical conformation of a protein
      dimer, given the structures of the two interacting proteins in their unbound
      state, is a difficult one. The location of the docking interface is determined
      largely by geometric complementarity, but finding complementary geometry is
      complicated by the flexibility of the backbone and side-chains of both proteins.
      We seek to generate candidates for docking that approximate the bound state well,
      even in cases where there is backbone and/or side-chain difference from unbound
      to bound states. RESULTS: We divide the surfaces of each protein into local
      patches and describe the effect of side-chain flexibility on each patch by
      sampling the space of conformations of its side-chains. Likely positions of
      individual side-chains are given by a rotamer library; this library is used to
      derive a sample of possible mutual conformations within the patch. We enforce
      broad coverage of torsion space. We control the size of the sample by using
      energy criteria to eliminate unlikely configurations, and by clustering similar
      configurations, resulting in 50 candidates for a patch, a manageable number for
      docking. CONCLUSIONS: Using a database of protein dimers for which the bound and
      unbound structures of the monomers are known, we show that from the unbound patch
      we are able to generate candidates for docking that approximate the bound
      structure. In patches where backbone change is small (within 1 A RMSD of bound),
      we are able to account for flexibility and generate candidates that are good
      approximations of the bound state (82% are within 1 A and 98% are within 1.4 A
      RMSD of the bound conformation). We also find that even in cases of moderate
      backbone flexibility our candidates are able to capture some of the overall shape
      change. Overall, in 650 of 700 test patches we produce a candidate that is either
      within 1 A RMSD of the bound conformation or is closer to the bound state than
      the unbound is.

PMID- 21092318
TI  - Suppression of nitric oxide production from nasal fibroblasts by metabolized
      clarithromycin in vitro.
AB  - BACKGROUND: Low-dose and long-term administration of 14-membered macrolide
      antibiotics, so called macrolide therapy, has been reported to favorably modify
      the clinical conditions of chronic airway diseases. Since there is growing
      evidence that macrolide antibiotic-resistant bacteria's spreaders in the
      populations received macrolide therapy, it is strongly desired to develop
      macrolide antibiotics, which showed only anti-inflammatory action. The present
      study was designed to examine the influence of clarithromycin (CAM) and its
      metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal
      polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of
      important effector molecule in the development of airway inflammatory disease in
      vitro. METHODS: NPFs (5 * 105 cells/ml) were stimulated with 1.0 MUg/ml
      lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in
      culture supernatants were examined by the Griess method. We also examined the
      influence of agents on the phosphorylation of MAPKs, NF-kappaB activation, iNOS
      mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours,
      respectively. RESULTS: The addition of CAM (> 0.4 MUg/ml) and M-4 (> 0.04 MUg/ml)
      could suppress NO production from NPFs after LPS stimulation through the
      suppression of iNOS mRNA expression and NF-kappaB activation. CAM and M-4 also
      suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are
      increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the
      NO generation, even when 0.1 MUg/ml of the agent was added to cell cultures.
      CONCLUSION: The present results may suggest that M-4 will be a good candidate for
      the agent in the treatment of chronic airway inflammatory diseases, since M-4 did
      not have antimicribiological effects on gram positive and negative bacteria.

PMID- 21092319
TI  - Bovine proteins containing poly-glutamine repeats are often polymorphic and
      enriched for components of transcriptional regulatory complexes.
AB  - BACKGROUND: About forty human diseases are caused by repeat instability
      mutations. A distinct subset of these diseases is the result of extreme
      expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding
      poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation
      is also apparent in human poly-Q encoding genes from normal individuals. As these
      coding sequence repeats are subject to selection in mammals, it has been
      suggested that normal variations in some of these typically highly conserved
      genes are implicated in morphological differences between species and phenotypic
      variations within species. At present, poly-Q encoding genes in non-human
      mammalian species are poorly documented, as are their functions and propensities
      for polymorphic variation. RESULTS: The current investigation identified 178
      bovine poly-Q encoding genes (Q >= 5) and within this group, 26 genes with
      orthologs in both human and mouse that did not contain poly-Q repeats. The bovine
      poly-Q encoding genes typically had ubiquitous expression patterns although there
      was bias towards expression in epithelia, brain and testes. They were also
      characterised by unusually large sizes. Analysis of gene ontology terms revealed
      that the encoded proteins were strongly enriched for functions associated with
      transcriptional regulation and many contributed to physical interaction networks
      in the nucleus where they presumably act cooperatively in transcriptional
      regulatory complexes. In addition, the coding sequence CAG repeats in some bovine
      genes impacted mRNA splicing thereby generating unusual transcriptional
      diversity, which in at least one instance was tissue-specific. The poly-Q
      encoding genes were prioritised using multiple criteria for their likelihood of
      being polymorphic and then the highest ranking group was experimentally tested
      for polymorphic variation within a cattle diversity panel. Extensive and
      meiotically stable variation was identified. CONCLUSIONS: Transcriptional
      diversity can potentially be generated in poly-Q encoding genes by the impact of
      CAG repeat tracts on mRNA alternative splicing. This effect, combined with the
      physical interactions of the encoded proteins in large transcriptional regulatory
      complexes suggests that polymorphic variations of proteins in these complexes
      have strong potential to affect phenotype.

PMID- 21092320
TI  - The use of chemotherapy regimens carrying a moderate or high risk of febrile
      neutropenia and the corresponding management of febrile neutropenia: an expert
      survey in breast cancer and non-Hodgkin's lymphoma.
AB  - BACKGROUND: The use of chemotherapy regimens with moderate or high risk of
      febrile neutropenia (defined as having a FN incidence of 10% or more) and the
      respective incidence and clinical management of FN in breast cancer and NHL has
      not been studied in Belgium. The existence of a medical need for G-CSF primary
      and secondary prophylaxis with these regimens was investigated in a real-life
      setting. METHODS: Nine oncologists and six hematologists from different Belgian
      general hospitals and university centers were surveyed to collect expert opinion
      and real-life data (year 2007) on the use of chemotherapy regimens with moderate
      or high risk of febrile neutropenia and the clinical management of FN in patients
      aged <65 years with breast cancer or NHL. Data were retrospectively obtained,
      over a 6-month observation period. RESULTS: The most frequently used regimens in
      breast cancer patients (n = 161) were FEC (45%), FEC-T (37%) and docetaxel alone
      (6%). In NHL patients (n = 39), R-CHOP-21 (33%) and R-ACVBP-14 (15%) were mainly
      used. Without G-CSF primary prophylaxis (PP), FN occurred in 31% of breast cancer
      patients, and 13% had PSN. After G-CSF secondary prophylaxis (SP), 4% experienced
      further FN events. Only 1 breast cancer patient received PP, and did not
      experience a severe neutropenic event. Overall, 30% of chemotherapy cycles
      observed in breast cancer patients were protected by PP/SP. In 10 NHL patients
      receiving PP, 2 (20%) developed FN, whereas 13 (45%) of the 29 patients without
      PP developed FN and 3 (10%) PSN. Overall, 55% of chemotherapy cycles observed in
      NHL patients were protected by PP/SP. Impaired chemotherapy delivery (timing
      and/or dose) was reported in 40% (breast cancer) and 38% (NHL) of patients
      developing FN. Based on oncologist expert opinion, hospitalization rates for FN
      (average length of stay) without and with PP were, respectively, 48% (4.2 days)
      and 19% (1.5 days). Similar rates were obtained from hematologists. CONCLUSIONS:
      Despite the studied chemotherapy regimens being known to be associated with a
      moderate or high risk of FN, upfront G-CSF prophylaxis was rarely used. The
      observed incidence of severe neutropenic events without G-CSF prophylaxis was
      higher than generally reported in the literature. The impact on medical resources
      used is sizeable.

PMID- 21092321
TI  - Biodiversity Conservation in the REDD.
AB  - Deforestation and forest degradation in the tropics is a major source of global
      greenhouse gas (GHG) emissions. The tropics also harbour more than half the
      world's threatened species, raising the possibility that reducing GHG emissions
      by curtailing tropical deforestation could provide substantial co-benefits for
      biodiversity conservation. Here we explore the potential for such co-benefits in
      Indonesia, a leading source of GHG emissions from land cover and land use change,
      and among the most species-rich countries in the world. We show that focal
      ecosystems for interventions to reduce emissions from deforestation and forest
      degradation in Indonesia do not coincide with areas supporting the most species
      rich communities or highest concentration of threatened species. We argue that
      inherent trade-offs among ecosystems in emission reduction potential, opportunity
      cost of foregone development and biodiversity values will require a regulatory
      framework to balance emission reduction interventions with biodiversity co
      benefit targets. We discuss how such a regulatory framework might function, and
      caution that pursuing emission reduction strategies without such a framework may
      undermine, not enhance, long-term prospects for biodiversity conservation in the
      tropics.

PMID- 21092322
TI  - Establishment of a new human pleomorphic malignant fibrous histiocytoma cell
      line, FU-MFH-2: molecular cytogenetic characterization by multicolor fluorescence
      in situ hybridization and comparative genomic hybridization.
AB  - BACKGROUND: Pleomorphic malignant fibrous histiocytoma (MFH) is one of the most
      frequent malignant soft tissue tumors in adults. Despite the considerable amount
      of research on MFH cell lines, their characterization at a molecular cytogenetic
      level has not been extensively analyzed. METHODS AND RESULTS: We established a
      new permanent human cell line, FU-MFH-2, from a metastatic pleomorphic MFH of a
      72-year-old Japanese man, and applied multicolor fluorescence in situ
      hybridization (M-FISH), UrovysionTM FISH, and comparative genomic hybridization
      (CGH) for the characterization of chromosomal aberrations. FU-MFH-2 cells were
      spindle or polygonal in shape with oval nuclei, and were successfully maintained
      in vitro for over 80 passages. The histological features of heterotransplanted
      tumors in severe combined immunodeficiency mice were essentially the same as
      those of the original tumor. Cytogenetic and M-FISH analyses displayed a
      hypotriploid karyotype with numerous structural aberrations. UrovysionTM FISH
      revealed a homozygous deletion of the p16INK4A locus on chromosome band 9p21. CGH
      analysis showed a high-level amplification of 9q31-q34, gains of 1p12-p34.3,
      2p21, 2q11.2-q21, 3p, 4p, 6q22-qter, 8p11.2, 8q11.2-q21.1, 9q21-qter, 11q13,
      12q24, 15q21-qter, 16p13, 17, 20, and X, and losses of 1q43-qter, 4q32-qter, 5q14
      q23, 7q32-qter, 8p21-pter, 8q23, 9p21-pter, 10p11.2-p13, and 10q11.2-q22.
      CONCLUSION: The FU-MFH-2 cell line will be a particularly useful model for
      studying molecular pathogenesis of human pleomorphic MFH.

PMID- 21092323
TI  - Calmodulin kinase II-dependent transactivation of PDGF receptors mediates
      astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid.
AB  - BACKGROUND: Lipoteichoic acid (LTA) is a component of Gram-positive bacterial
      cell walls, which has been found to be elevated in cerebrospinal fluid of
      patients suffering from meningitis. Moreover, matrix metalloproteinases (MMPs),
      MMP-9 especially, have been observed in patients with brain inflammatory diseases
      and may contribute to brain disease pathology. However, the molecular mechanisms
      underlying LTA-induced MMP-9 expression in brain astrocytes remain unclear.
      OBJECTIVE: The goal of this study was to examine whether LTA-induced cell
      migration is mediated by calcium/calmodulin (CaM)/CaM kinase II (CaMKII)
      dependent transactivation of the PDGFR pathway in rat brain astrocytes (RBA-1
      cells). METHODS: Expression and activity of MMP-9 induced by LTA was evaluated by
      zymographic, western blotting, and RT-PCR analyses. MMP-9 regulatory signaling
      pathways were investigated by treatment with pharmacological inhibitors or using
      dominant negative mutants or short hairpin RNA (shRNA) transfection, and
      chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays.
      Finally, we determined the cell functional changes by cell migration assay.
      RESULTS: The data show that c-Jun/AP-1 mediates LTA-induced MMP-9 expression in
      RBA-1 cells. Next, we demonstrated that LTA induces MMP-9 expression via a
      calcium/CaM/CaMKII-dependent transactivation of PDGFR pathway. Transactivation of
      PDGFR led to activation of PI3K/Akt and JNK1/2 and then activated c-Jun/AP-1
      signaling. Activated-c-Jun bound to the AP-1-binding site of the MMP-9 promoter,
      and thereby turned on transcription of MMP-9. Eventually, up-regulation of MMP-9
      by LTA enhanced cell migration of astrocytes. CONCLUSIONS: These results
      demonstrate that in RBA-1 cells, activation of c-Jun/AP-1 by a CaMKII-dependent
      PI3K/Akt-JNK activation mediated through transactivation of PDGFR is essential
      for up-regulation of MMP-9 and cell migration induced by LTA. Understanding the
      regulatory mechanisms underlying LTA-induced MMP-9 expression and functional
      changes in astrocytes may provide a new therapeutic strategy for Gram-positive
      bacterial infections in brain disorders.

PMID- 21092324
TI  - Identification and expression analysis of microRNAs and targets in the biofuel
      crop sugarcane.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small regulatory RNAs, some of which are
      conserved in diverse plant genomes. Therefore, computational identification and
      further experimental validation of miRNAs from non-model organisms is both
      feasible and instrumental for addressing miRNA-based gene regulation and
      evolution. Sugarcane (Saccharum spp.) is an important biofuel crop with publicly
      available expressed sequence tag and genomic survey sequence databases, but
      little is known about miRNAs and their targets in this highly polyploid species.
      RESULTS: In this study, we have computationally identified 19 distinct sugarcane
      miRNA precursors, of which several are highly similar with their sorghum homologs
      at both nucleotide and secondary structure levels. The accumulation pattern of
      mature miRNAs varies in organs/tissues from the commercial sugarcane hybrid as
      well as in its corresponding founder species S. officinarum and S. spontaneum.
      Using sugarcane MIR827 as a query, we found a novel MIR827 precursor in the
      sorghum genome. Based on our computational tool, a total of 46 potential targets
      were identified for the 19 sugarcane miRNAs. Several targets for highly conserved
      miRNAs are transcription factors that play important roles in plant development.
      Conversely, target genes of lineage-specific miRNAs seem to play roles in diverse
      physiological processes, such as SsCBP1. SsCBP1 was experimentally confirmed to
      be a target for the monocot-specific miR528. Our findings support the notion that
      the regulation of SsCBP1 by miR528 is shared at least within graminaceous
      monocots, and this miRNA-based post-transcriptional regulation evolved
      exclusively within the monocots lineage after the divergence from eudicots.
      CONCLUSIONS: Using publicly available nucleotide databases, 19 sugarcane miRNA
      precursors and one new sorghum miRNA precursor were identified and classified
      into 14 families. Comparative analyses between sugarcane and sorghum suggest that
      these two species retain homologous miRNAs and targets in their genomes. Such
      conservation may help to clarify specific aspects of miRNA regulation and
      evolution in the polyploid sugarcane. Finally, our dataset provides a framework
      for future studies on sugarcane RNAi-dependent regulatory mechanisms.

PMID- 21092325
TI  - Tracking hantavirus nucleocapsid protein using intracellular antibodies.
AB  - BACKGROUND: Hantavirus nucleocapsid (N) protein is a multifunctional viral
      macromolecule involved in multiple stages of the viral replication cycle. The
      intracellular trafficking of N protein during virus assembly remains unclear.
      METHODS: We used N protein-specific intracellular expressed antibodies to track
      the localization and distribution of Hantaan virus and Seoul virus N protein. The
      N protein-specific antibody single-chain variable antibody fragments (scFvs),
      which bind an N-terminal linear epitope (L13F3) and C-terminal conformational
      domain (H34), were intracellularly expressed in the endoplasmic reticulum (ER) by
      fusion of the SEKDEL retention signal peptide at the carboxyl terminus, and in
      the cytoplasm (Cyto) by deletion of the ER membrane target signal peptide. Stable
      Vero-E6 cell lines expressing intracellular scFvs were either infected with
      hantavirus or transfected with an N protein expression plasmid; virus replication
      and N protein intracellular localization were determined. RESULT: N protein co
      localized with scFvs in the ER and cytoplasm with or without viral membrane
      glycoproteins. Hantavirus replication was inhibited in both the scFvs-ER- and
      scFvs-Cyto-expressing stable cell lines. CONCLUSION: N protein may be expressed
      in the ER retention signal peptide of KDEL circulating region (ER/cis-Golgi)
      without the assistance of G protein, and so expression of N protein in both the
      cytoplasm and within the ER/cis-Golgi plays an important role in virus
      replication.

PMID- 21092326
TI  - Geographical, meteorological and vectorial factors related to malaria re
      emergence in Huang-Huai River of central China.
AB  - BACKGROUND: Malaria still represents a significant public health problem in
      China, and the cases dramatically increased in the areas along the Huang-Huai
      River of central China after 2001. Considering spatial aggregation of malaria
      cases and specific vectors, the geographical, meteorological and vectorial
      factors were analysed to determine the key factors related to malaria re
      emergence in these particular areas. METHODS: The geographic information of 357
      malaria cases and 603 water bodies in 113 villages were collected to analyse the
      relationship between the residence of malaria cases and water body. Spearman rank
      correlation, multiple regression, curve fitting and trend analysis were used to
      explain the relationship between the meteorological factors and malaria
      incidence. Entomological investigation was conducted in two sites to get the
      vectorial capacity and the basic reproductive rate to determine whether the
      effect of vector lead to malaria re-emergence. RESULTS: The distances from
      household of cases to the nearest water-body was positive-skew distributed, the
      median was 60.9 m and 74% malaria cases were inhabited in the extent of 60 m near
      the water body, and the risk rate of people live there attacked by malaria was
      higher than others(OR = 1.6, 95%CI (1.042, 2.463), P < 0.05). The annual average
      temperature and rainfall may have close relationship with annual incidence. The
      average monthly temperature and rainfall were the key factors, and the
      correlation coefficients are 0.501 and 0.304(P < 0.01), respectively. Moreover,
      75.3% changes of monthly malaria incidence contributed to the average monthly
      temperature (T(mean)), the average temperature of last two months(T(mean01)) and
      the average rainfall of current month (R(mean)) and the regression equation was Y
      = -2.085 + 0.839I1 + 0.998T(mean0) - 0.86T(mean01) + 0.16R(mean0). All the
      collected mosquitoes were Anopheles sinensis. The vectorial capacity and the
      basic reproductive rate of An. sinensis in two sites were 0.6969, 0.4983 and
      2.1604, 1.5447, respectively. CONCLUSION: The spatial distribution between
      malaria cases and water-body, the changing of meteorological factors, and
      increasing vectorial capacity and basic reproductive rate of An. sinensis leaded
      to malaria re-emergence in these areas.

PMID- 21092327
TI  - NSP2 gene variation of the North American genotype of the Thai PRRSV in central
      Thailand.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a major swine
      pathogen causing economic losses in the swine industry almost worldwide. PRRSV
      has been divided into 2 genotypes, the European (Type 1) and North American (Type
      2) genotype, respectively and displays a large degree of genetic variability,
      particularly at the nonstructural protein (nsp) 2 gene. This is the first study
      determining genetic variation of the nsp2 of Thai PRRSV isolates. The results
      showed that 9 out of 10 Thai PRRSV isolates were nsp2-truncated viruses that
      might have evolved from a virus previously introduced in the past, but not from
      one recently introduced.

PMID- 21092328
TI  - The genome-scale metabolic network analysis of Zymomonas mobilis ZM4 explains
      physiological features and suggests ethanol and succinic acid production
      strategies.
AB  - BACKGROUND: Zymomonas mobilis ZM4 is a Gram-negative bacterium that can
      efficiently produce ethanol from various carbon substrates, including glucose,
      fructose, and sucrose, via the Entner-Doudoroff pathway. However, systems
      metabolic engineering is required to further enhance its metabolic performance
      for industrial application. As an important step towards this goal, the genome
      scale metabolic model of Z. mobilis is required to systematically analyze in
      silico the metabolic characteristics of this bacterium under a wide range of
      genotypic and environmental conditions. RESULTS: The genome-scale metabolic model
      of Z. mobilis ZM4, ZmoMBEL601, was reconstructed based on its annotated genes,
      literature, physiological and biochemical databases. The metabolic model
      comprises 579 metabolites and 601 metabolic reactions (571 biochemical conversion
      and 30 transport reactions), built upon extensive search of existing knowledge.
      Physiological features of Z. mobilis were then examined using constraints-based
      flux analysis in detail as follows. First, the physiological changes of Z.
      mobilis as it shifts from anaerobic to aerobic environments (i.e. aerobic shift)
      were investigated. Then the intensities of flux-sum, which is the cluster of
      either all ingoing or outgoing fluxes through a metabolite, and the maximum in
      silico yields of ethanol for Z. mobilis and Escherichia coli were compared and
      analyzed. Furthermore, the substrate utilization range of Z. mobilis was expanded
      to include pentose sugar metabolism by introducing metabolic pathways to allow Z.
      mobilis to utilize pentose sugars. Finally, double gene knock-out simulations
      were performed to design a strategy for efficiently producing succinic acid as
      another example of application of the genome-scale metabolic model of Z. mobilis.
      CONCLUSION: The genome-scale metabolic model reconstructed in this study was able
      to successfully represent the metabolic characteristics of Z. mobilis under
      various conditions as validated by experiments and literature information. This
      reconstructed metabolic model will allow better understanding of Z. mobilis
      metabolism and consequently designing metabolic engineering strategies for
      various biotechnological applications.

PMID- 21092329
TI  - Validation and characterization of DNA microarray gene expression data
      distribution and associated moments.
AB  - BACKGROUND: The data from DNA microarrays are increasingly being used in order to
      understand effects of different conditions, exposures or diseases on the
      modulation of the expression of various genes in a biological system. This
      knowledge is then further used in order to generate molecular mechanistic
      hypotheses for an organism when it is exposed to different conditions. Several
      different methods have been proposed to analyze these data under different
      distributional assumptions on gene expression. However, the empirical validation
      of these assumptions is lacking. RESULTS: Best fit hypotheses tests, moment-ratio
      diagrams and relationships between the different moments of the distribution of
      the gene expression was used to characterize the observed distributions. The data
      are obtained from the publicly available gene expression database, Gene
      Expression Omnibus (GEO) to characterize the empirical distributions of gene
      expressions obtained under varying experimental situations each of which
      providing relatively large number of samples for hypothesis testing. All data
      were obtained from either of two microarray platforms--the commercial Affymetrix
      mouse 430.2 platform and a non-commercial Rosetta/Merck one. The data from each
      platform were preprocessed in the same manner. CONCLUSIONS: The null hypotheses
      for goodness of fit for all considered univariate theoretical probability
      distributions (including the Normal distribution) are rejected for more than 50%
      of probe sets on the Affymetrix microarray platform at a 95% confidence level,
      suggesting that under the tested conditions a priori assumption of any of these
      distributions across all probe sets is not valid. The pattern of null hypotheses
      rejection was different for the data from Rosetta/Merck platform with only around
      20% of the probe sets failing the logistic distribution goodness-of-fit test. We
      find that there are statistically significant (at 95% confidence level based on
      the F-test for the fitted linear model) relationships between the mean and the
      logarithm of the coefficient of variation of the distributions of the logarithm
      of gene expressions. An additional novel statistically significant quadratic
      relationship between the skewness and kurtosis is identified. Data from both
      microarray platforms fail to identify with any one of the chosen theoretical
      probability distributions from an analysis of the l-moment ratio diagram.

PMID- 21092331
TI  - Quantitative pinch stimulator for exploring evoked nociceptive responses: a pilot
      study.
AB  - BACKGROUND: A mechanical noxious stimulator is useful for studies of pain, both
      for clinic and basic research. We propose to use a pinch stimulator that can not
      only generate a quantitative, reproducible noxious pinch but also simultaneously
      provide a synchronous external trigger signal, which is essential for acquisition
      of evoked potentials. METHODS: For ethical considerations, audible and visual
      aids were incorporated so that pinch force could be regulated within a
      predetermined level. Reproducibility of the nociceptive responses evoked by this
      device was validated. The device was constructed with a simple circuit, and the
      element build-in was delicately selected for the minimum required to produce
      evoked potentials. RESULTS: The magnitude of the force output is linearly
      proportional to the volts produced by the device (i.e., during the pinch).
      Increases in force correspond to increases in the number of action potentials
      induced. CONCLUSIONS: This device may be useful for studying the mechanisms of
      nociceptive signal processing in the brain through application of reproducible,
      noxious pinch stimuli.

PMID- 21092330
TI  - Identification and validation of genes involved in gastric tumorigenesis.
AB  - BACKGROUND: Gastric cancer is one of the common cancers seen in south India.
      Unfortunately more than 90% are advanced by the time they report to a tertiary
      centre in the country. There is an urgent need to characterize these cancers and
      try to identify potential biomarkers and novel therapeutic targets. MATERIALS AND
      METHODS: We used 24 gastric cancers, 20 Paired normal (PN) and 5 apparently
      normal gastric tissues obtained from patients with non-gastric cancers
      (Apparently normal - AN) for the microarray study followed by validation of the
      significant genes (n = 63) by relative quantitation using Taqman Low Density
      Array Real Time PCR. We then used a custom made Quantibody protein array to
      validate the expression of 15 proteins in gastric tissues (4 AN, 9 PN and 9
      gastric cancers). The same array format was used to study the plasma levels of
      these proteins in 58 patients with gastric cancers and 18 from patients with
      normal/non-malignant gastric conditions. RESULTS: Seventeen genes (ASPN,
      CCL15/MIP-1delta, MMP3, SPON2, PRSS2, CCL3, TMEPAI/PMEPAI, SIX3, MFNG, SOSTDC1,
      SGNE1, SST, IGHA1, AKR1B10, FCGBP, ATP4B, NCAPH2) were shown to be differentially
      expressed between the tumours and the paired normal, for the first time. EpCAM (p
      = 0.0001), IL8 (p = 0.0003), CCL4/MIP-1beta (p = 0.0026), CCL20/MIP-3alpha (p =
      0.039) and TIMP1 (p = 0.0017) tissue protein levels were significantly different
      (Mann Whitney U test) between tumours versus AN & PN. In addition, median plasma
      levels of IL8, CXCL9/MIG, CCL3/MIP-1alpha, CCL20/MIP-3alpha, PDGFR-B and TIMP1
      proteins were significantly different between the non-malignant group and the
      gastric cancer group. The post-surgical levels of EpCAM, IGFBP3, IL8,
      CXCL10/IP10, CXCL9/MIG, CCL3/MIP-1alpha, CCL20/MIP-3alpha, SPP1/OPN and PDGFR-B
      showed a uniform drop in all the samples studied. CONCLUSIONS: Our study has
      identified several genes differentially expressed in gastric cancers, some for
      the first time. Some of these have been confirmed at the protein level, as well.
      Some of these proteins will need to be evaluated further for their potential as
      diagnostic biomarkers in gastric cancers and some could be useful as follow-up
      markers in gastric cancer.

PMID- 21092332
TI  - Late-onset peritoneal recurrence of advanced gastric cancer 20 years after
      primary resection.
AB  - Late onset of peritoneal recurrence of gastric cancer more than 10 years after
      surgery is extremely rare, and only three cases have been reported. We present
      the case of a 61-year-old man who was diagnosed finally with peritoneal
      recurrence of gastric cancer 20 years after primary curative resection. As a
      result of small-bowel obstruction caused by peritoneal recurrence, diverting
      ileostomy with partial ileal resection was performed. The resected specimen
      revealed tubular adenocarcinoma that resembled the primary gastric cancer. The
      clinical course after the second operation was unfavorable and systemic
      chemotherapy had no effect. He died at 62 years of age, 21 years and 7 months
      after initial gastrectomy. Immunohistochemical analysis using antibodies against
      proliferating cell nuclear antigen (PCNA), Ki-67, and p53 was performed to
      investigate the phenotype of primary and recurrence cancer. Protein expression of
      proliferation markers such as PCNA and Ki-67 was down-regulated, but p53 was
      overexpressed at the site of recurrence. These data suggest that late peritoneal
      recurrence has a low proliferation rate and is resistant to chemoradiotherapy. In
      conclusion, we present late onset of peritoneal recurrence of gastric cancer more
      than 20 years after primary surgery, and speculate on the mechanism of late-onset
      recurrence in our case.

PMID- 21092333
TI  - Clinical evaluation of Dyslipidemia among type II diabetic patients at Public
      hospital Penang, Malaysia.
AB  - BACKGROUND: Global views emphasize the need for early; effective intervention
      against the atherogenic dyslipidemia associated with type 2 diabetes and
      metabolic syndrome to reduce the risk of premature cardiovascular diseases. Our
      aim was to determine the clinical practices and compliance among dyslipidemia
      with type II diabetes and hypertension in multiracial society. METHOD(S): Study
      was carried out in out-patient department of General hospital Penang over a
      period of ten months (Jan - Oct 2008). Study reflects the retrospective data
      collection covering a period of three years from Jan 2005 - Dec 2007. Universal
      sampling technique was used to select all the patients' undergone treatment for
      diabetes type II and dyslipidemia. All the concerned approvals were obtained from
      Clinical research Committee (CRC). Data was analyzed by using SPSS 15(r).
      RESULT(S): A total of 501 diabetes type 2 patients with dyslipidemia were
      identified in this study. The demographic data showed that 55.9% (n = 280) were
      female patients and 44.1% (n = 221) were males. Patients on combination therapy
      of metformin with other antidiabetic agent were 79%, while 21% were on
      monotherapy. Lovastatin was received as monotherapy in 83% of study population,
      while only 17% were on combination with gemfibrozil. Means of FPG and lipid
      profile were reduced from the initial (2005) to the latest level (2007)
      significantly (p < 0.001). Only 0.89% decrease in mean weight with S.D 13.1 as
      compared to initial S.D 12.8 after three years of Cohort. While in description
      35.2% representatives gain weight with majority of males (71.5%), 52.3% with
      weight loss of 1-3 pounds majority (69.3%) with female respondents and rest 12.4%
      remains with same weight with mix gender distribution. CONCLUSION: Metformin and
      lovastatin use among patients of type 2 diabetes and dyslipidemia is
      significantly improved the clinical outcomes. No significant association of
      metformin or lovastatin is found against the hypertension. Metformin and calcium
      channel blocker combination therapy was found to be the best choice in the co
      treatment of diabetes and hypertension.

PMID- 21092335
TI  - Welcome to investigative genetics.

PMID- 21092334
TI  - Relationship between radiographic changes and symptoms or physical examination
      findings in subjects with symptomatic medial knee osteoarthritis: a three-year
      prospective study.
AB  - BACKGROUND: Although osteoarthritis (OA) of the knee joints is the most common
      and debilitating joint disease in developed countries, the factors that determine
      the severity of symptoms are not yet understood well. Subjects with symptomatic
      medial knee OA were followed up prospectively to explore the relationship between
      radiographic changes and symptoms or physical examination findings. METHODS: One
      hundred six OA knees in 68 subjects (mean age 71.1 years; 85% women) were
      followed up at 6-month intervals over 36 months. At each visit, knee radiographs
      were obtained, symptoms were assessed by a validated questionnaire, and the
      result of physical examination was recorded systematically using a specific
      chart. Correlations between the change of radiographs and clinical data were
      investigated in a longitudinal manner. RESULTS: During the study period, the
      narrowing of joint space width (JSW) was observed in 34 joints (32%). Although
      those knees were clinically or radiographically indistinguishable at baseline
      from those without JSW narrowing, differences became apparent at later visits
      during the follow-up. The subjects with knees that underwent JSW narrowing had
      severer symptoms, and the symptoms tended to be worse for those with higher rates
      of narrowing. A significant correlation was not found between the severity of
      symptoms and the growth of osteophytes. For the knees that did not undergo
      radiographic progression, the range of motion improved during the follow-up
      period, possibly due to the reduction of knee pain. Such improvement was not
      observed with the knees that underwent JSW narrowing or osteophyte growth.
      CONCLUSION: The result of this study indicates that the symptoms of knee OA
      patients tend to be worse when JSW narrowing is underway. This finding may
      explain, at least partly, a known dissociation between the radiographic stage of
      OA and the severity of symptoms.

PMID- 21092336
TI  - Tales the double helix tells.

PMID- 21092337
TI  - Is the NIH policy for sharing GWAS data running the risk of being
      counterproductive?
AB  - Through their current policy on data sharing, the National Institutes of Health
      (NIH) are inadvertently placing a serious and potentially insuperable burden upon
      non-US researchers who perform patient-based genomics studies in collaboration
      with US institutions. Because this policy could adversely affect future
      transnational scientific collaborations, we explore some of its likely
      consequences and suggest possible courses of remedial action wherever feasible.

PMID- 21092339
TI  - Development of a single base extension method to resolve Y chromosome haplogroups
      in sub-Saharan African populations.
AB  - BACKGROUND: The ability of the Y chromosome to retain a record of its evolution
      has seen it become an essential tool of molecular anthropology. In the last few
      years, however, it has also found use in forensic genetics, providing information
      on the geographic origin of individuals. This has been aided by the development
      of efficient screening methods and an increased knowledge of geographic
      distribution. In this study, we describe the development of single base extension
      assays used to resolve 61 Y chromosome haplogroups, mainly within haplogroups A,
      B and E, found in Africa. RESULTS: Seven multiplex assays, which incorporated 60
      Y chromosome markers, were developed. These resolved Y chromosomes to 61 terminal
      branches of the major African haplogroups A, B and E, while also including a few
      Eurasian haplogroups found occasionally in African males. Following its
      validation, the assays were used to screen 683 individuals from Southern Africa,
      including south eastern Bantu speakers (BAN), Khoe-San (KS) and South African
      Whites (SAW). Of the 61 haplogroups that the assays collectively resolved, 26
      were found in the 683 samples. While haplogroup sharing was common between the
      BAN and KS, the frequencies of these haplogroups varied appreciably. Both groups
      showed low levels of assimilation of Eurasian haplogroups and only two
      individuals in the SAW clearly had Y chromosomes of African ancestry.
      CONCLUSIONS: The use of these single base extension assays in screening increased
      haplogroup resolution and sampling throughput, while saving time and DNA. Their
      use, together with the screening of short tandem repeat markers would
      considerably improve resolution, thus refining the geographic ancestry of
      individuals.

PMID- 21092340
TI  - Accurate, rapid and high-throughput detection of strain-specific polymorphisms in
      Bacillus anthracis and Yersinia pestis by next-generation sequencing.
AB  - BACKGROUND: In the event of biocrimes or infectious disease outbreaks, high
      resolution genetic characterization for identifying the agent and attributing it
      to a specific source can be crucial for an effective response. Until recently, in
      depth genetic characterization required expensive and time-consuming Sanger
      sequencing of a few strains, followed by genotyping of a small number of marker
      loci in a panel of isolates at or by gel-based approaches such as pulsed field
      gel electrophoresis, which by necessity ignores most of the genome. Next
      generation, massively parallel sequencing (MPS) technology (specifically the
      Applied Biosystems sequencing by oligonucleotide ligation and detection (SOLiDTM)
      system) is a powerful investigative tool for rapid, cost-effective and parallel
      microbial whole-genome characterization. RESULTS: To demonstrate the utility of
      MPS for whole-genome typing of monomorphic pathogens, four Bacillus anthracis and
      four Yersinia pestis strains were sequenced in parallel. Reads were aligned to
      complete reference genomes, and genomic variations were identified. Resequencing
      of the B. anthracis Ames ancestor strain detected no false-positive single
      nucleotide polymorphisms (SNPs), and mapping of reads to the Sterne strain
      correctly identified 98% of the 133 SNPs that are not clustered or associated
      with repeats. Three geographically distinct B. anthracis strains from the A
      branch lineage were found to have between 352 and 471 SNPs each, relative to the
      Ames genome, and one strain harbored a genomic amplification. Sequencing of four
      Y. pestis strains from the Orientalis lineage identified between 20 and 54 SNPs
      per strain relative to the CO92 genome, with the single Bolivian isolate having
      approximately twice as many SNPs as the three more closely related North American
      strains. Coverage plotting also revealed a common deletion in two strains and an
      amplification in the Bolivian strain that appear to be due to insertion element
      mediated recombination events. Most private SNPs (that is, a, variant found in
      only one strain in this set) selected for validation by Sanger sequencing were
      confirmed, although rare false-positive SNPs were associated with variable
      nucleotide tandem repeats. CONCLUSIONS: The high-throughput, multiplexing
      capability, and accuracy of this system make it suitable for rapid whole-genome
      typing of microbial pathogens during a forensic or epidemiological investigation.
      By interrogating nearly every base of the genome, rare polymorphisms can be
      reliably discovered, thus facilitating high-resolution strain tracking and
      strengthening forensic attribution.

PMID- 21092338
TI  - Identifying experimental surrogates for Bacillus anthracis spores: a review.
AB  - Bacillus anthracis, the causative agent of anthrax, is a proven biological
      weapon. In order to study this threat, a number of experimental surrogates have
      been used over the past 70 years. However, not all surrogates are appropriate for
      B. anthracis, especially when investigating transport, fate and survival.
      Although B. atrophaeus has been widely used as a B. anthracis surrogate, the two
      species do not always behave identically in transport and survival models.
      Therefore, we devised a scheme to identify a more appropriate surrogate for B.
      anthracis. Our selection criteria included risk of use (pathogenicity),
      phylogenetic relationship, morphology and comparative survivability when
      challenged with biocides. Although our knowledge of certain parameters remains
      incomplete, especially with regards to comparisons of spore longevity under
      natural conditions, we found that B. thuringiensis provided the best overall fit
      as a non-pathogenic surrogate for B. anthracis. Thus, we suggest focusing on this
      surrogate in future experiments of spore fate and transport modelling.

PMID- 21092341
TI  - A rare variant of the mtDNA HVS1 sequence in the hairs of Napoleon's family.
AB  - This paper describes the finding of a rare variant in the sequence of the
      hypervariable segment (HVS1) of mitochondrial (mtDNA) extracted from two
      preserved hairs, authenticated as belonging to the French Emperor Napoleon I
      (Napoleon Bonaparte). This rare variant is a mutation that changes the base C to
      T at position 16,184 (16184C->T), and it constitutes the only mutation found in
      this HVS1 sequence. This mutation is rare, because it was not found in a
      reference database (P < 0.05). In a personal database (M. Pala) comprising 37,000
      different sequences, the 16184C->T mutation was found in only three samples, thus
      in this database the mutation frequency was 0.00008%. This mutation 16184C->T was
      also the only variant found subsequently in the HVS1 sequences of mtDNAs
      extracted from Napoleon's mother (Letizia) and from his youngest sister
      (Caroline), confirming that this mutation is maternally inherited. This 16184C->T
      variant could be used for genetic verification to authenticate any doubtful
      material and determine whether it should indeed be attributed to Napoleon.

PMID- 21092342
TI  - Factors affecting the STR amplification success in poorly preserved bone samples.
AB  - BACKGROUND: Factors affecting the success of short tandem repeat (STR)
      amplification of poorly preserved samples are generally known, but as of yet,
      they have seldom been systematically assessed. Using two different maximum
      likelihood-based methods, the relative importance of DNA quantity, degradation
      and inhibition in STR genotyping was studied with DNA extracts from a set of old
      bone samples. First, the effects of different factors related to PCR
      amplification were estimated with a generalized linear mixed model. Second, error
      rates of allelic drop-out and drop-in were estimated on the basis of the
      frequency and nature of mismatches between replicates. RESULTS: In autosomal STR
      analyses, the most important factor was the DNA quantity, followed by the
      degradation, whereas in Y-chromosomal STR analysis, the most important factor was
      the degradation. Inhibition was a minor concern in STR analyses of poorly
      preserved bones. CONCLUSIONS: The success of PCR amplification depends largely on
      the template DNA quality (amount and degradation), but these problems can be
      partly compensated for by different primer design and amplification chemistry.
      Consequently, the relative roles of the compromising factors differ according to
      the kit used.

PMID- 21092343
TI  - DNA identification by pedigree likelihood ratio accommodating population
      substructure and mutations.
AB  - DNA typing is an important tool in missing-person identification, especially in
      mass-fatality disasters. Identification methods comparing a DNA profile from
      unidentified human remains with that of a direct (from the person) or indirect
      (for example, from a biological relative) reference sample and ranking the
      pairwise likelihood ratios (LR) is straightforward and well defined. However, for
      indirect comparison cases in which several members from a family can serve as
      reference samples, the full power of kinship analysis is not entirely exploited.
      Because biologically related family members are not genetically independent, more
      information and thus greater power can be attained by simultaneous use of all
      pedigree members in most cases, although distant relationships may reduce the
      power. In this study, an improvement was made on the method for missing-person
      identification for autosomal and lineage-based markers, by considering jointly
      the DNA profile data of all available family reference samples. The missing
      person is evaluated by a pedigree LR of the probability of DNA evidence under
      alternative hypotheses (for example, the missing person is unrelated or if they
      belong to this pedigree with a specified biological relationship) and can be
      ranked for all pedigrees within a database. Pedigree LRs are adjusted for
      population substructure according to the recommendations of the second National
      Research Council (NRCII) Report. A realistic mutation model was also incorporated
      to accommodate the possibility of false exclusion. The results show that the
      effect of mutation on the pedigree LR is moderate, but LRs can be significantly
      decreased by the effect of population substructure. Finally, Y chromosome and
      mitochondrial DNA were integrated into the analysis to increase the power of
      identification. A program titled MPKin was developed, combining the
      aforementioned features to facilitate genetic analysis for identifying missing
      persons. The computational complexity of the algorithms is explained, and several
      ways to reduce the complexity are introduced.

PMID- 21092344
TI  - An epidemiological perspective on the future of direct-to-consumer personal
      genome testing.
AB  - Personal genome testing is offered via the internet directly to consumers. Most
      tests that are currently offered use data from genome-wide scans to predict risks
      for multiple common diseases and traits. The utility of these tests is limited,
      predominantly because they lack predictive ability and clear benefits for disease
      prevention that are specific for genetic risk groups. In the near future,
      personal genome tests will likely be based on whole genome sequencing, but will
      these technological advances increase the utility of personal genome testing?
      Whole genome sequencing theoretically provides information about the risks of
      both monogenic and complex diseases, but the practical utility remains to be
      demonstrated. The utility of testing depends on the predictive ability of the
      test, the likelihood of actionable test results, and the options available for
      the reduction of risks. For monogenic diseases, the likelihood of known mutations
      will be extremely low in the general population and it will be a challenge to
      recognize new causal variants among all rare variants that are found using
      sequencing. For complex diseases, the predictive ability of genetic tests will be
      mainly restricted by the heritability of the disease, but also by the genetic
      complexity of the disease etiology, which determines the extent to which the
      heritability can be understood. Given that numerous genetic and non-genetic risk
      factors interact in the causation of complex diseases, the predictive ability of
      genetic models will likely remain modest. Personal genome testing will have
      minimal benefits for individual consumers unless major breakthroughs are made in
      the near future.

PMID- 21092345
TI  - The ghost and the machine.

PMID- 21092346
TI  - Forensic identification of severely degraded Atlantic salmon (Salmo salar) and
      rainbow trout (Oncorhynchus mykiss) tissues.
AB  - BACKGROUND: Aquaculture is a globally important and rapidly growing industry. It
      contributes positively to the economy and sustainability of coastal communities,
      but it is not without regulatory challenges. These challenges are diverse, and
      may include identification of fish discarded in an illegal manner, biological
      discharge from fish ensilage tanks, and partially destroyed or processed tissues.
      Robust genetic tools are required by management authorities to address these
      challenges. In this paper, we describe nine species-specific primer sets
      amplifying very short DNA fragments within the mitochondrial DNA cytochrome c
      oxidase (COI) gene, which were designed to permit diagnostic identification of
      degraded DNA from two of the most commonly farmed salmonids in Europe and North
      America. RESULTS: Of the nine designed primer sets, six were found to be species
      specific (four Atlantic salmon, two rainbow trout), whereas the remaining three
      sets (two Atlantic salmon, one rainbow trout) also amplified a product from
      other, closely related, salmonid DNA templates. Screening of DNA templates from
      11 other non-salmonid native fish species did not produce PCR products with any
      of the primer sets. Specific tests confirmed the ability of these markers to
      identify Atlantic salmon and rainbow trout tissues in treated food products,
      chemically treated ensilage waste and fillets left to degrade in saltwater for up
      to 31 days at 15 degrees C. Importantly, these markers provided diagnostic
      identification in cases where other genetic methods failed because of degraded
      DNA quality. CONCLUSIONS: Results from this study demonstrate that amplification
      of very short DNA fragments using species-specific primers represents a robust
      and versatile method to create cheap and efficient genetic tests that can be
      implemented in a range of forensic applications. These markers will provide
      fishery, aquaculture and food regulatory authorities with a method to investigate
      and enforce regulations within these industries.

PMID- 21092347
TI  - Abstracts of the 16th Scientific Symposium of the Austrian Pharmacological
      Society (APHAR). Vienna, Austria. November 25-27, 2010.

PMID- 21092348
TI  - [Hypertension in young women: remember oral contraceptives].
AB  - Three women, aged 18, 31 and 36 years, presented with hypertension while taking
      oral contraceptives. Each patient had received antihypertensive drugs. Blood
      pressure returned to normal within weeks of cessation of oral contraceptives.
      Although the reduction in hormone content seems to have reduced the risk of oral
      contraceptive-induced hypertension, there is still an increased risk. As the
      prevalence of hypertension in women aged under 45 is low, the possibility that
      the hypertension is caused by contraceptives should be considered in women of
      childbearing age. Discontinuation may cause a significant decrease in blood
      pressure and should be encouraged before commencing antihypertensive agents.
      Alternative methods of contraception include the progestogen-only pill or a
      mechanical contraceptive device.

PMID- 21092349
TI  - Identification of Trichinella spiralis early antigens at the pre-adult and adult
      stages.
AB  - Three expression cDNA libraries from Trichinella spiralis worms 14 h, 20 h and 48
      h post-infection (p.i.) were screened with serum from pigs experimentally
      infected with 20,000 T. spiralis muscle larvae. Twenty-nine positive clones were
      isolated from the 14 h p.i. cDNA library, corresponding to 8 different genes. A
      putative excretory-secretory protein similar to that of T. pseudospiralis was
      identified. Three clones corresponded to a T. spiralis serine proteinase
      inhibitor known to be involved in diverse functions such as blood coagulation and
      modulation of inflammation. Screening of the 20 h p.i. cDNA library selected 167
      positive clones representing 12 different sequences. The clone with the highest
      redundancy encoded a small polypeptide having no sequence identity with any known
      proteins from Trichinella or other organisms. Fourteen clones displayed sequence
      identity with the heat shock protein (HSP) 70. HSPs are produced as an adaptive
      response of the parasite to the hostile environment encountered in the host
      intestine but their mechanism of action is not yet well defined. From the 48 h
      p.i. T. spiralis cDNA library, 91 positive clones were identified representing 7
      distinct sequences. Most of the positive clones showed high similarity with a
      member of a putative T. spiralis serine protease family. This result is
      consistent with a possible major role for serine proteases during invasive stages
      of Trichinella infection and host-parasite interactions.

PMID- 21092350
TI  - Contrast processing by ON and OFF bipolar cells.
AB  - Much of what is currently known about the visual response of retinal bipolar
      cells is based on studies of rod-dominant responses to flashes in the dark in the
      isolated retina. This minireview summarizes quantitative findings on contrast
      processing in the intact light-adapted retina based on intracellular recording
      from more than 400 cone-driven bipolar cells in the tiger salamander: 1) In the
      main, the contrast responses of ON and OFF cells are surprisingly similar,
      suggesting a need to refine the view that ON and OFF cells provide the selective
      substrates for processing of positive and negative contrasts, respectively. 2)
      Overall, the response is quite nonlinear, showing very high gain for small
      contrasts, some 10-15 times greater than that of cones, but then quickly
      approaches saturation for higher contrasts. 3) Under optimal conditions of light
      adaptation, both classes of bipolar cells show evidence for efficient coding with
      respect to the contrasts in natural images. 4) There is a marked diversity within
      both the ON and OFF bipolar cell populations and an absence of discrete subtypes.
      The dynamic ranges bracket the range of contrasts in nature. 5) For both ON and
      OFF cells, the receptive field organization shows a striking symmetry between
      center and surround for responses of the same polarity and thus opposite contrast
      polarities. 6) The latency difference between ON and OFF cells is about 30 ms,
      which seems qualitatively consistent with a delay due to the G-protein cascade in
      ON bipolar cells. 7) In sum, we report quantitative evidence for at least 11
      transformations in signal processing that occur between the voltage response of
      cones and the voltage response of bipolar cells.

PMID- 21092351
TI  - Operationalization of the updated diagnostic algorithm for classifying HIV
      related cognitive impairment and dementia.
AB  - BACKGROUND: This study applies the updated HIV-Associated Neurocognitive
      Disorders (HAND) diagnostic algorithm. METHODS: Participants were 210 HIV
      infected-adults, classified using proposed HAND criteria: HIV-Associated Dementia
      (HAD), Mild Neurocognitive Disorder (MND), Asymptomatic Neurocognitive Impairment
      (ANI). RESULTS: The algorithm yielded: normal = 32.8%, ANI = 21.4%, MND = 34.3%,
      and HAD = 11.4%. Normal participants performed superior to HAND-defined
      participants on cognition, and HAD participants performed more poorly on global
      cognition and executive functioning. Two distinct subgroups of interest emerged:
      (1) functional decline without cognitive impairment; (2) severe cognitive
      impairment and minimal functional compromise. CONCLUSIONS: The algorithm
      discriminates between HIV-infected cognitively impaired individuals. Diagnosis
      yields two unique profiles requiring further investigation. Findings largely
      support the algorithm's utility for diagnosing HIV-cognitive-impairment, but
      suggest distinct subsets of individuals with discrepant cognitive/functional
      performances that may not be readily apparent by conventional application of HAND
      diagnosis.

PMID- 21092352
TI  - Psychogeriatric inpatient unit design: a literature review.
AB  - BACKGROUND: In many parts of the world the provision of psychogeriatric inpatient
      units (PGUs) remains limited. More units will be required over coming decades
      given rapid population aging. METHODS: Medline (1950-2010), psycINFO (1806-2009),
      EMBASE (1980-2009) and CINAHL (1982-2009) were searched for papers about PGU
      design. Selected non-peer reviewed literature such as government reports and
      unpublished academic dissertations were also reviewed. Data were also obtained
      from the literature related to general adult psychiatry inpatient units where
      there was limited information from studies of units designed for older people.
      Over 200 papers were reviewed and 130 were included. RESULTS: There are few good
      quality studies to guide the design of acute PGUs and much of the existing
      literature is based on opinion and anecdote or, at best, based on observational
      studies. Randomized controlled studies comparing different designs and assessing
      outcomes are virtually non-existent. Several studies have identified violence and
      trauma resulting from hospitalization as significant problems with current acute
      PGU care. Despite its limitations the available literature provides useful
      guidance on how PGU design can optimize patient and staff safety and improve
      clinical outcomes. CONCLUSIONS: There are significant problems with current acute
      PGUs, and patient mix on existing units is an important issue. Future research
      should examine patient and staff perceptions of different PGU ward environments,
      the relationship between ward design and clinical outcomes, the effects of
      segregating patients with challenging behaviors in dementia and the benefits or
      otherwise of gender segregation.

PMID- 21092353
TI  - Preliminary evaluation of culturally sensitive CBT for depression in Pakistan:
      findings from Developing Culturally-sensitive CBT Project (DCCP).
AB  - BACKGROUND: There is sufficient research evidence in favour of cognitive therapy
      in western world. However, only limited research has been carried out on its
      effectiveness in other countries. It is suggested that adaptations in content,
      format and delivery are needed before CBT can be employed in non-western
      cultures. We describe a preliminary evaluation of culturally adapted CBT for
      depression in Pakistan. AIMS: We aimed to evaluate the efficacy of this
      culturally adapted CBT using a therapist manual. METHOD: In a randomized
      controlled trial we compared combination of CBT and antidepressants with
      antidepressants alone (treatment as usual) in primary care. Referred patients
      with ICD-10 diagnosis of depression were invited to participate and randomized to
      the intervention and control groups. Hospital Anxiety and Depression Scale (HADS)
      and Bradford Somatic Inventory (BSI) were used to measure changes in depression,
      anxiety and somatic symptoms. RESULTS: Seventeen patients each were randomized to
      each arms of the trial. Except for financial status there were no differences
      between the two groups on various demographic variables. Patients receiving CBT
      showed statistically significant improvement on measures of depression (p <
      .001), anxiety (p < .001) and somatic symptoms (p < .000) as compared to
      antidepressant alone group. 82% patients attended six or more sessions of
      therapy. CONCLUSIONS: A culturally sensitive manualized CBT was effective in
      reducing symptoms of depression and anxiety in Pakistan.

PMID- 21092354
TI  - The Australian brain and cognition and antiepileptic drugs study: IQ in school
      aged children exposed to sodium valproate and polytherapy.
AB  - Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with
      increased risk of birth defects and cognitive impairment in young children. We
      evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in
      school-aged children. Fifty-seven children exposed to VPA (n = 23), polytherapy
      with VPA (n = 15), or polytherapy without VPA (n = 19) were assessed using the
      Wechsler Intelligence Scale for Children--Fourth Edition. Information on maternal
      epilepsy, pregnancy, and medical history was obtained prospectively through the
      Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All
      groups had elevated frequencies of Extremely Low (<70) or Borderline (70-79) Full
      Scale IQ (15.8-40.0%). Verbal Comprehension and Working Memory scores in all
      groups fell significantly below the standardized test mean, while Perceptual
      Reasoning and Processing Speed scores were relatively intact. Multivariate
      analysis of covariance analysis revealed significant main effects of VPA on
      Verbal Comprehension and Working Memory, and of polytherapy on Verbal
      Comprehension and Processing Speed. Our results suggest that VPA has a dose
      dependent negative impact on verbal intellectual abilities, and may also affect
      working memory. The possibility that inclusion of VPA in many polytherapy
      regimens may underlie reduced mean scores of polytherapy-exposed children is
      discussed.

PMID- 21092355
TI  - Neuropsychology 3.0: evidence-based science and practice.
AB  - Neuropsychology is poised for transformations of its concepts and methods,
      leveraging advances in neuroimaging, the human genome project, psychometric
      theory, and information technologies. It is argued that a paradigm shift toward
      evidence-based science and practice can be enabled by innovations, including (1)
      formal definition of neuropsychological concepts and tasks in cognitive
      ontologies; (2) creation of collaborative neuropsychological knowledgebases; and
      (3) design of Web-based assessment methods that permit free development, large
      sample implementation, and dynamic refinement of neuropsychological tests and the
      constructs these aim to assess. This article considers these opportunities,
      highlights selected obstacles, and offers suggestions for stepwise progress
      toward these goals.

PMID- 21092357
TI  - Testate amoebae examined by confocal and two-photon microscopy: implications for
      taxonomy and ecophysiology.
AB  - Testate amoebae (TA) are a group of free-living protozoa, important in ecology
      and paleoecology. Testate amoebae taxonomy is mainly based on the morphological
      features of the shell, as examined by means of light microscopy or
      (environmental) scanning electron microscopy (SEM/ESEM). We explored the
      potential applications of confocal laser scanning microscopy (CLSM), two photon
      excitation microscopy (TPEM), phase contrast, differential interference contrast
      (DIC Nomarski), and polarization microscopy to visualize TA shells and inner
      structures of living cells, which is not possible by SEM or environmental SEM.
      Images captured by CLSM and TPEM were utilized to create three-dimensional (3D)
      visualizations and to evaluate biovolume inside the shell by stereological
      methods, to assess the function of TA in ecosystems. This approach broadens the
      understanding of TA cell and shell morphology, and inner structures including
      organelles and endosymbionts, with potential implications in taxonomy and
      ecophysiology.

PMID- 21092356
TI  - Neural correlates of interference control in adolescents with traumatic brain
      injury: functional magnetic resonance imaging study of the counting stroop task.
AB  - Difficulty in inhibition or cognitive control is a common and significant sequela
      of pediatric traumatic brain injury (TBI). The present study used functional MRI
      to examine one specific inhibitory function, interference control, in 11
      adolescents, aged 12-16 years, (mean age, 15.7 years) with TBI who were at least
      1 year postinjury and 11 age-matched typically developing control participants
      (TC) (mean age, 15.2 years). Participants completed a Counting Stroop task with 2
      main conditions: (1) a neutral condition requiring the counting of animal words
      and (2) an interference condition in which mismatched number words were counted.
      Both TBI and TC adolescents activated similar networks of brain regions relevant
      to interference control, but the TBI group showed higher levels of activation
      relative to the TC group in multiple brain areas within this network, including
      predominantly right frontal and parietal regions. Findings of greater activation
      of the relevant neural network in the TBI group are consistent with recent fMRI
      findings using other interference control paradigms with individuals with a
      history of TBI.

PMID- 21092358
TI  - The inclusion of functional foods enriched in fibre, calcium, iodine, fat-soluble
      vitamins and  n-3 fatty acids in a conventional diet improves the nutrient
      profile according to the Spanish reference intake.
AB  - OBJECTIVE: The growing interest in maintaining good health status through optimal
      nutrition has boosted the launch of a number of functional foods on the market.
      The objective of the present study was to theoretically evaluate the nutritional
      relevance of incorporating selected enriched foods in the diet. DESIGN: A 28 d
      dietary plan, designed to be balanced under the recommended macronutrients
      criteria, was used as a basal diet. Some conventional foods were exchanged with
      foods enriched in fibre, calcium, iodine, vitamins A, D, E or n-3 fatty acids.
      SETTING: Nutritional composition of basal and modified diets was derived and
      compared to the Spanish recommended intakes (RI). RESULTS: The basal diet covered
      the recommendations for fibre and calcium with mean intake of 28 g and 1241 mg,
      respectively. The current intake of salt, if iodized, or bread elaborated with
      this salt, allowed reaching the daily intake of iodine every day, with a mean
      supply of 216 MUg/d and 278 MUg/d, respectively. The deficient supply of vitamin
      E in the basal diet (mean = 8 mg/d) was covered by including enriched margarine
      and dairy products (mean = 15 mg/d). The low n-3 fatty acids intake in the basal
      diet (1.1 g/d) increased up to 1.9 g/d after the use of enriched margarine,
      butter and biscuits and soya drink instead of milk. CONCLUSIONS: In order to
      improve the accomplishment of the RI iodine, vitamin E and n-3 fatty acids,
      interesting strategies dealing with the incorporation of enriched foods in the
      diet were successfully initiated.

PMID- 21092359
TI  - Mindfulness groups for psychosis; key issues for implementation on an inpatient
      unit.
AB  - BACKGROUND: There is emerging evidence that mindfulness groups for people with
      distressing psychosis are safe and therapeutic. AIMS: The present study aimed to
      investigate the feasibility of running and evaluating a mindfulness group on an
      inpatient ward for individuals with chronic and treatment resistant psychosis.
      METHOD: Eight participants attended a 6-week mindfulness group on a specialist
      tertiary inpatient ward. RESULTS: This study demonstrated that mindfulness
      exercises were acceptable and well-tolerated by participants. Measuring outcome,
      systemic challenges and participant experience are discussed.

PMID- 21092360
TI  - Socialization to the model: the active component in the therapeutic alliance? A
      preliminary study.
AB  - BACKGROUND: Therapeutic alliance has been found to be a significant predictor of
      outcome in psychotherapy yet what constitutes therapeutic alliance remains
      unclear. Examining the common constructs of therapeutic alliance, it is possible
      that there may be a conceptual overlap between active components of therapeutic
      alliance and socialization to the treatment model. AIM: To investigate the
      relationship between socialization to the model and therapeutic alliance. METHOD:
      Participants (N = 43) were taken from the active treatment arm in a RCT for the
      treatment of chronic fatigue syndrome (CFS/ME). Therapeutic alliance was measured
      using a 5-item questionnaire (brief CALPAS) and socialization to the model was
      extracted from therapy tapes using a novel coding system. RESULTS: Key findings
      were that when patients and therapists agreed about goals of treatment, there
      were higher levels of concordance, less evidence of applying principles
      incongruent to the model, and less resistance during the treatment sessions.
      CONCLUSIONS: The outcome of this preliminary study contributes to the potential
      understanding of active components in the therapeutic alliance, and supports
      further research to achieve a more detailed picture of "non-specific" factors in
      therapy, including the active process of socialization in therapeutic alliance.

PMID- 21092362
TI  - Intelligence in Taiwan: Progressive Matrices means and sex differences in means
      and variances for 6- to 17-year-olds.
AB  - Data for Raven's Progressive Matrices are reported for a sample of 6290 6- to 17
      year-olds in Taiwan. The Taiwanese obtained a mean IQ of 109.5, in relation to a
      British mean of 100. There was no difference in mean scores of boys and girls at
      age 7 years. At age 10 years girls obtained significantly higher scores than
      boys, and at ages 13 and 16 years boys obtained significantly higher scores than
      girls. There was no sex difference in variance at age 7 years. At ages 10, 13 and
      16 years variance was significantly greater in boys.

PMID- 21092366
TI  - Is equol production beneficial to health?
AB  - The health benefits associated with soya food consumption have been widely
      studied, with soya isoflavones and soya protein implicated in the protection of
      CVD, osteoporosis and cancers such as those of the breast and prostate. Equol (7
      hydroxy-3-(4'-hydroxyphenyl)-chroman), a metabolite of the soya isoflavone
      daidzein, is produced via the formation of the intermediate dihydrodaidzein, by
      human intestinal bacteria, with only approximately 30-40% of the adult population
      having the ability to perform this transformation following a soya challenge.
      Inter-individual variation in conversion of daidzein to equol has been
      attributed, in part, to differences in the diet and in gut microflora
      composition, although the specific bacteria responsible for the colonic
      biotransformation of daidzein to equol are yet to be identified. Equol is a
      unique compound in that it can exert oestrogenic effects, but is also a potent
      antagonist of dihydrotestosterone in vivo. Furthermore, in vitro studies suggest
      that equol is more biologically active than its parent compound, daidzein, with a
      higher affinity for the oestrogen receptor and a more potent antioxidant
      activity. Although some observational and intervention studies suggest that the
      ability to produce equol is associated with reduced risk of breast and prostate
      cancer, CVD, improved bone health and reduced incidence of hot flushes, others
      have reported null or adverse effects. Studies to date have been limited and well
      designed studies that are sufficiently powered to investigate the relationship
      between equol production and disease risk are warranted before the clinical
      relevance of the equol phenotype can be fully elucidated.

PMID- 21092361
TI  - Understanding ethnic differences in behaviour relating to Schistosoma mansoni re
      infection after mass treatment.
AB  - It is now widely recognized that a decentralized approach to the control of
      parasitic infections in rural sub-Saharan populations allows for the design of
      more effective control programmes and encourages high compliance. Compliance is
      usually an indicator of treatment success, but cannot be used as a measure of
      long-term benefit since re-infection will be strongly influenced by a number of
      factors including the social ecology of a community. In this paper qualitative
      and quantitative methods are used to identify and understand the structural and
      behavioural constraints that may influence water contact behaviour and create
      inequalities with respect to Schistosoma re-infection following anti-helminth
      drug treatment. The research is set in a community where participant engagement
      has remained uniformly high throughout the course of a 10-year multidisciplinary
      study on treatment and re-infection, but where levels of re-infection have not
      been uniform and, because of variations in water contact behaviour, have varied
      by age, sex and ethnic background. Variations in the biomedical knowledge of
      schistosomiasis, socioeconomic constraints and ethnic differences in general
      attitudes towards life and health are identified that may account for some of
      these behavioural differences. The observations highlight the benefits of
      understanding the socio-ecology of control and research settings at several
      levels (both between and within ethnic groups); this will help to design more
      effective and universally beneficial interventions for control and help to
      interpret research findings.

PMID- 21092365
TI  - Obesity, sarcopenia and their functional consequences in old age.
AB  - The prevalence of obesity is high in older persons and recent trends show a rapid
      increase in this prevalence. Results from observational and intervention studies
      (i.e. weight loss studies) show the strong negative impact of obesity on
      functional status in old age. There are different potential pathways through
      which obesity may lead to functional decline in older persons. Furthermore, the
      presence of overweight and obesity during the life course and trends in medical
      care are likely to influence the impact of obesity on disability. The concepts
      sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of
      muscle strength) receive a lot of research attention as potential determinants of
      functional decline in old age. There is no consensus on the definitions of these
      concepts. Recent studies conducted in large cohort studies of mainly community
      dwelling older persons show that poor muscle strength is strongly associated with
      functional decline compared to low muscle mass. In several studies, no
      association between muscle mass and functional status was observed. Current
      research on the combination of obesity with poor muscle strength (dynapenic
      obesity) suggests a potential additive effect of both components on poor
      functional status in old age which seems independent of the level of physical
      activity.

PMID- 21092368
TI  - The science of muscle hypertrophy: making dietary protein count.
AB  - Growing evidence supports the conclusion that consumption of protein in close
      temporal proximity to the performance of resistance exercise promotes greater
      muscular hypertrophy. We can also state with good certainty that merely consuming
      energy, as carbohydrate for example, is also not sufficient to maximise muscle
      protein synthesis leading to anabolism and net new muscle protein accretion.
      Recent work also indicates that certain types of proteins, particular those that
      are rapidly digested and high in leucine content (i.e. whey protein), appear to
      be more efficient at stimulating muscle protein synthesis. Continued practice of
      consumption of these types or proteins after exercise should lead to greater
      hypertrophy. Reviews of numerous training studies indicate that studies in which
      milk proteins and principally whey protein show an advantage of these proteins
      over and above isoenergetic carbohydrate and soya protein in promoting
      hypertrophy. Thus, the combined evidence suggests a strategic advantage of
      practising early post-exercise consumption of whey protein or dairy-based protein
      to promote muscle protein synthesis, net muscle protein accretion and ultimately
      hypertrophy.

PMID- 21092364
TI  - Dietary protein and exercise training in ageing.
AB  - Ageing is accompanied by a progressive loss of skeletal muscle mass and strength,
      leading to the loss of functional capacity and an increased risk for developing
      chronic metabolic diseases such as diabetes. The age-related loss of skeletal
      muscle mass results from a chronic disruption in the balance between muscle
      protein synthesis and degradation. As basal muscle protein synthesis rates are
      likely not different between healthy young and elderly human subjects, it was
      proposed that muscles from older adults lack the ability to regulate the protein
      synthetic response to anabolic stimuli, such as food intake and physical
      activity. Indeed, the dose-response relationship between myofibrillar protein
      synthesis and the availability of essential amino acids and/or resistance
      exercise intensity is shifted down and to the right in elderly human subjects.
      This so-called 'anabolic resistance' represents a key factor responsible for the
      age-related decline in skeletal muscle mass. Interestingly, long-term resistance
      exercise training is effective as a therapeutic intervention to augment skeletal
      muscle mass, and improves functional performance in the elderly. The consumption
      of different types of proteins, i.e. protein hydrolysates, can have different
      stimulatory effects on muscle protein synthesis in the elderly, which may be due
      to their higher rate of digestion and absorption. Current research aims to
      elucidate the interactions between nutrition, exercise and the skeletal muscle
      adaptive response that will define more effective strategies to maximise the
      therapeutic benefits of lifestyle interventions in the elderly.

PMID- 21092367
TI  - Genetic variation in taste perception: does it have a role in healthy eating?
AB  - Taste is often cited as the factor of greatest significance in food choice, and
      has been described as the body's 'nutritional gatekeeper'. Variation in taste
      receptor genes can give rise to differential perception of sweet, umami and
      bitter tastes, whereas less is known about the genetics of sour and salty taste.
      Over twenty-five bitter taste receptor genes exist, of which TAS2R38 is one of
      the most studied. This gene is broadly tuned to the perception of the bitter
      tasting thiourea compounds, which are found in brassica vegetables and other
      foods with purported health benefits, such as green tea and soya. Variations in
      this gene contribute to three thiourea taster groups of people: supertasters,
      medium tasters and nontasters. Differences in taster status have been linked to
      body weight, alcoholism, preferences for sugar and fat levels in food and fruit
      and vegetable preferences. However, genetic predispositions to food preferences
      may be outweighed by environmental influences, and few studies have examined
      both. The Tastebuddies study aimed at taking a holistic approach, examining both
      genetic and environmental factors in children and adults. Taster status, age and
      gender were the most significant influences in food preferences, whereas genotype
      was less important. Taster perception was associated with BMI in women;
      nontasters had a higher mean BMI than medium tasters or supertasters. Nutrient
      intakes were influenced by both phenotype and genotype for the whole group, and
      in women, the AVI variation of the TAS2R38 gene was associated with a nutrient
      intake pattern indicative of healthy eating.

PMID- 21092370
TI  - Lexical tone awareness among Chinese children with developmental dyslexia.
AB  - This study examined the extent and nature of lexical tone deficit in Chinese
      developmental dyslexia. Twenty Cantonese-speaking Chinese dyslexic children (mean
      age 8;11) were compared to twenty average readers of the same age (CA control
      group, mean age 8;11), and another twenty younger average readers of the same
      word reading level (RL control group, mean age 7;4) on different measures of
      lexical tone awareness, rhyme awareness and visual-verbal paired-associate
      learning. Results showed that the Chinese dyslexic children performed
      significantly worse than the CA but not the RL control groups in nearly all the
      lexical tone and rhyme awareness measures. Analyses of individual performance
      demonstrated that over one-third of the dyslexic children showed a deficit in
      some aspects of tone awareness. Tone discrimination and tone production were
      found to correlate significantly with Chinese word reading. These findings
      confirm that Chinese dyslexic children show weaknesses in tone awareness.

PMID- 21092371
TI  - Mutual exclusivity and phonological novelty constrain word learning at 16 months.
AB  - Studies report that infants as young as 1 ; 3 to 1 ; 5 will seek out a novel
      object in response to hearing a novel label (e.g. Halberda, 2003; Markman, Wasow
      & Hansen, 2003). This behaviour is commonly known as the 'mutual exclusivity'
      response (Markman, 1989; 1990). However, evidence for mutual exclusivity does not
      imply that the infant has associated a novel label with a novel object. We used
      an intermodal preferential looking task to investigate whether infants aged 1 ; 4
      could use mutual exclusivity to guide their association of novel labels with
      novel objects. The results show that infants can successfully map a novel label
      onto a novel object, provided that the novel label has no familiar phonological
      neighbours. Therefore, as early as 1 ; 4, infants can use mutual exclusivity to
      form novel word-object associations, although this process is constrained by the
      phonological novelty of a label.

PMID- 21092369
TI  - Structure, function and mechanism of the anaphase promoting complex (APC/C).
AB  - The complex molecular events responsible for coordinating chromosome replication
      and segregation with cell division and growth are collectively known as the cell
      cycle. Progression through the cell cycle is orchestrated by the interplay
      between controlled protein synthesis and degradation and protein phosphorylation.
      Protein degradation is primarily regulated through the ubiquitin proteasome
      system, mediated by two related E3 protein ubiquitin ligases, the Skp1 cullin F
      box (SCF) and the anaphase promoting complex (also known as the cyclosome)
      (APC/C). The APC/C is a multi-subunit cullin-RING E3 ubiquitin ligase that
      regulates progression through the mitotic phase of the cell cycle and controls
      entry into S phase by catalysing the ubiquitylation of cyclins and other cell
      cycle regulatory proteins. Selection of APC/C targets is controlled through
      recognition of short destruction motifs, predominantly the D-box and KEN-box.
      APC/C-mediated coordination of cell cycle progression is achieved through the
      temporal regulation of APC/C activity and substrate specificity, exerted through
      a combination of co-activator subunits, reversible phosphorylation and inhibitory
      proteins and complexes. The aim of this article is to discuss the APC/C from a
      structural and mechanistic perspective. Although an atomic structure of the APC/C
      is still lacking, a combination of genetic, biochemical, electron microscopy
      studies of intact APC/C and crystallographic analysis of individual subunits,
      together with analogies to evolutionarily related E3 ligases of the RING family,
      has provided deep insights into the molecular mechanisms of catalysis and
      substrate recognition, and structural organisation of the APC/C.

PMID- 21092363
TI  - Contemporary nutritional transition: determinants of diet and its impact on body
      composition.
AB  - The world has experienced a marked shift in the global BMI distribution towards
      reduced undernutrition and increased obesity. The collision between human
      biology, shaped over the millennia and modern technology, globalization,
      government policies and food industry practices have worked to create far
      reaching energy imbalance across the globe. A prime example is the clash between
      our drinking habits and our biology. The shift from water and breast milk as the
      only beverages available, to a vast array of caloric beverages was very rapid,
      shaped both by our tastes and aggressive marketing of the beverage industry. Our
      biology, shaped over millennia by daily consumption of water and seasonal
      availability of food, was not ready to compensate for the liquid energies. Other
      dietary changes were similarly significant, particularly the shift towards
      increased frequency of eating and larger portions. The roles of the food and
      beverage production, distribution and marketing sectors in not only shaping our
      diet but also accelerating these changes must be understood. Apart from the role
      of beverages, there is much less consensus about the role of various components
      of our diet in energy imbalance. Understanding the determinants of change in the
      key components of our diet through an array of research provides insights into
      some of the options we face in attempting to attain a great balance between
      energy intake and expenditures while creating an overall healthier dietary
      pattern. A few countries are systematically addressing the causes of poor dietary
      and physical activity patterns and high energy imbalance.

PMID- 21092377
TI  - Is there any additional evidence for the epidemiological transition hypothesis of
      elderly suicides?

PMID- 21092381
TI  - Diapause and its regulation in the whitefly Trialeurodes lauri.
AB  - This study focuses on the regulation of synchronization between the life cycle of
      the oligophagous whitefly, Trialeurodes lauri (Signoret), and its evergreen host
      tree Arbutus andrachne in Mediterranean chaparral. Whitefly infestations vary
      considerably among trees. The adults of the univoltine (one generation per year)
      whitefly emerge en masse during April and May and oviposit on the new spring
      foliage. Following approximately one month of development to the early fourth
      instar, the nymphs enter nine-month diapauses, terminating in February. This
      diapause is induced and maintained by the plant and can be experimentally avoided
      (in the case of developing young nymphs) or terminated (in the case of diapausing
      fourth instars), if whitefly-bearing branches are severed from the tree and
      placed in water under laboratory conditions. This study is the first report of a
      whitefly diapausing through both summer and winter seasons. The role of the host
      plant in the process is discussed.

PMID- 21092372
TI  - The effect of feeding modified soyabean oil enriched with C18 : 4 n-3 to broilers
      on the deposition of n-3 fatty acids in chicken meat.
AB  - Supplementing broiler diets with conventional vegetable oils has little effect on
      the long-chain n-3 PUFA (LC n-3 PUFA) content of the meat. The present study
      investigated the effect on fatty acid composition and sensory characteristics of
      chicken meat when broilers were fed oil extracted from soyabeans (SDASOY) that
      had been genetically engineered to produce C18 : 4n-3 (stearidonic acid (SDA),
      240 mg/g oil). Three diets were fed to 120 birds (eight replicate pens of five
      birds) from 15 d to slaughter (41-50 d). Diets were identical apart from the oil
      added to them (45 and 50 g/kg as fed in the grower and finisher phases,
      respectively), which was either SDASOY, near-isogenic soya (CON) or fish oil
      (FISH). The LC n-3 PUFA content of the meat increased in the order CON, SDASOY
      and FISH. In breast meat with skin, the SDA concentration was 522, 13 and 37 (sem
      14.4) mg/100 g meat for SDASOY, CON and FISH, respectively. Equivalent values for
      C20 : 5n-3 (EPA) were 53, 13 and 140 (sem 8.4); for C22 : 5n-3 (docosapentaenoic
      acid (DPA)) 65, 15 and 101 (sem 3.5); for C22 : 6n-3 (DHA) 19, 9 and 181 (sem
      4.4). Leg meat (with skin) values for SDA were 861, 23 and 68 (sem 30.1); for EPA
      87, 9 and 258 (sem 7.5); for DPA 95, 20 and 165 (sem 5.0); for DHA 29, 10 and 278
      (sem 8.4). Aroma, taste and aftertaste of freshly cooked breast meat were not
      affected. Fishy aromas, tastes and aftertastes were associated with LC n-3 PUFA
      content of the meat, being most noticeable in the FISH leg meat (both freshly
      cooked and reheated) and in the reheated SDASOY leg meat.

PMID- 21092382
TI  - Pre-digestion of dietary lipids has only minor effects on absorption, retention
      and metabolism in larval stages of Atlantic cod (Gadus morhua).
AB  - The hypothesis of the present study was that cod larvae have a limitation in
      lipid digestion, and that absorption of lipids would increase by pre
      hydrolysation. The diets used were designed to contain 15% lipid, of which 40%
      was phosphatidylcholine (PC) and 60 % was TAG. Cod larvae (40d post hatch (dph))
      were fed a single meal where either PC or TAG was radioactively labelled, and the
      labelled PC or TAG was either intact or hydrolysed (pre-digested). The larvae
      were then incubated individually in chambers with collection of CO2 for 10 h. The
      following fractions were analysed for radioactivity: the incubation water
      (evacuated feed); the intestine; the body; the CO2 trap. The larvae ate a 16-29
      MUg diet, equivalent to 3.4-5.2 % of dry body weight. In the whole population, 0
      16% of the lipid was evacuated. The larvae that had eaten less than 1.9-2.7 MUg
      lipid absorbed close to 100% of the lipid, absorption being defined
      conservatively as the amount contained in the carcass and CO2, excluding the
      intestinal tissue. In these larvae, approximately 100 % of the absorbed lipid was
      also catabolised. In the larvae that ingested more than 1.9-2.7 MUg lipid, there
      was a linear reduction in lipid absorption to a minimum of 55% at the highest
      lipid intakes parallel to an increasing retention of lipids in the carcass. There
      were only minor differences in digestion, absorption, retention and metabolism of
      lipids between the larvae fed the different diets, and the larvae tended to
      retain lipid classes as they were present in the feed. The study shows that 40
      dph Atlantic cod larvae have an efficient utilisation of dietary lipids supplied
      as intact PC and TAG.

PMID- 21092378
TI  - Pathways to inflated responsibility beliefs in adolescent obsessive-compulsive
      disorder: a preliminary investigation.
AB  - BACKGROUND: An inflated sense of responsibility is characteristic of obsessive
      compulsive disorder (OCD). No previous studies have investigated its origins.
      Five potential pathways to inflated responsibility beliefs have been proposed;
      these are tested in this study. METHOD: A novel measure, the Origins
      Questionnaire for Adolescents (OQA), was developed to assess experiences on these
      five pathways. Reliability of the OQA was investigated. The experiences on the
      five pathways to inflated responsibility beliefs of 16 adolescents with a history
      of OCD were compared to 16 adolescents with no history of OCD. Parents also
      reported on adolescents' experiences on the five pathways. RESULTS: Test-retest
      reliability was high. The internal consistency of the subscales was only partly
      satisfactory. The groups differed on one pathway; the clinical group reported a
      higher sense of responsibility for significant incidents with a negative outcome
      prior to onset of OCD. CONCLUSIONS: An inflated sense of responsibility, in
      combination with the occurrence of specific incidents, might act as a
      vulnerability factor for development of OCD. Future research should consider how
      to measure the subtle effects of experiences of responsibility over the course of
      development.

PMID- 21092374
TI  - Inhibition of gametogenesis by the cestode Ligula intestinalis in roach (Rutilus
      rutilus) is attenuated under laboratory conditions.
AB  - Reproductive parameters of Ligula intestinalis-infected roach (Rutilus rutilus)
      which were held under long-tem laboratory conditions with unlimited food supply
      were investigated. Although uninfected and infected roach showed no difference in
      condition factor and both groups deposited perivisceral fat, the gonadosomatic
      index was significantly lower in infected female and male roach. Quantitative
      histological analysis revealed that gonad development was retarded upon
      parasitization in both genders. In contrast to the phenotype described in the
      field, infected females were able to recruit follicles into secondary growth, but
      a high percentage of secondary growth follicles underwent atresia. In both
      genders, the histological data corresponded well with reduced expression of
      pituitary gonadotropins and lowered plasma concentrations of sex steroids, as
      revealed by real-time RT-PCR and ELISA, respectively. Furthermore, a reduction of
      vitellogenin mRNA and modulated expression of sex steroid receptors in the liver
      was demonstrated. Like in the field, there was a significant adverse impact of L.
      intestinalis on host reproductive physiology which could not be related to
      parasite burden. Our results show, for the first time, that maintenance under
      laboratory conditions can not abolish the deleterious effect of L. intestinalis
      on gametogenesis in roach, and indicate a specific inhibition of host
      reproduction by endocrine disruption.

PMID- 21092379
TI  - Development of specific ITS markers for plant DNA identification within
      herbivorous insects.
AB  - DNA-based techniques have proved to be very useful methods to study trophic
      relationships between pests and their natural enemies. However, most predators
      are best defined as omnivores, and the identification of plant-specific DNA
      should also allow the identification of the plant species the predators have been
      feeding on. In this study, a PCR approach based on the development of specific
      primers was developed as a self-marking technique to detect plant DNA within the
      gut of one heteropteran omnivorous predator (Macrolophus pygmaeus) and two
      lepidopteran pest species (Helicoverpa armigera and Tuta absoluta). Specific
      tomato primers were designed from the ITS 1-2 region, which allowed the
      amplification of a tomato DNA fragment of 332 bp within the three insect species
      tested in all cases (100% of detection at t=0) and did not detect DNA of other
      plants nor of the starved insects. Plant DNA half-lives at 25 degrees C ranged
      from 5.8 h, to 27.7 h and 28.7 h within M. pygmaeus, H. armigera and T. absoluta,
      respectively. Tomato DNA detection within field-collected M. pygmaeus suggests
      dietary mixing in this omnivorous predator and showed a higher detection of
      tomato DNA in females and nymphs than males. This study provides a useful tool to
      detect and to identify plant food sources of arthropods and to evaluate crop
      colonization from surrounding vegetation in conservation biological control
      programs.

PMID- 21092376
TI  - Regulatory mechanisms of intestinal folate uptake in a rat model of folate
      oversupplementation.
AB  - Folic acid is essential for numerous biological functions, ranging from
      nucleotide biosynthesis to the remethylation of homocysteine. Folic acid is
      unable to cross the biological membranes by simple diffusion, so there exists a
      well-developed epithelial folate transport system for the regulation of normal
      folate homeostasis in the intestine. Any perturbances in the folate uptake system
      might lead to a state of folate deficiency, which in turn is strongly associated
      with the risk of various cancers, birth defects and CVD. Countries with
      obligatory folate fortification of food (USA and Canada) have documented a
      significant decrease in neural tube defects in newborns. However, the effect of
      folate oversupplementation on the intestinal absorption of folic acid has not
      been studied. We studied the process of folate transport and the expression of
      folate transporters in the rat intestine after folate oversupplementation. Rats
      were oversupplemented with tenfold the normal requirement of folic acid for
      periods of 10 and 60 d. Folate uptake in intestinal brush-border membrane
      vesicles followed saturable kinetics with pH optimum at 5.5. Acute, but not
      chronic, folate oversupplementation led to a significant down-regulation in
      intestinal folate uptake at acidic pH optima and was associated with a decrease
      in Vmax without any significant change in the Km of the folate uptake process.
      The decrease in folate uptake was also associated with the down-regulation in the
      protein levels of major folate transporters, proton-coupled folate transporter
      (PCFT) and reduced folate carrier (RFC), without altering their mRNA levels.
      Hence, it was concluded that acute folate oversupplementation results in a
      significant decrease in intestinal folate uptake by down-regulating the
      expressions of RFC and PCFT, via some post-transcriptional or translational
      mechanisms.

PMID- 21092375
TI  - Modulation of rat hepatic and kidney phase II enzymes by cabbage juices:
      comparison with the effects of indole-3-carbinol and phenethyl isothiocyanate.
AB  - The effect of raw cabbage and sauerkraut juices on the expression and activity of
      phase II enzymes, glutathione S-transferase (GST) and NAD(P)H:quinone
      oxidoreductase 1 (NQO1), in the rat liver and kidney was compared with that of
      two commercially available products of glucosinolate degradation: indole-3
      carbinol (I3C) and phenethyl isothiocyanate (PEITC). Male Wistar rats were
      treated by oral administration with cabbage juices, I3C or PEITC for 4, 10 and 30
      d. The results showed that juices, particularly sauerkraut juice as with I3C and
      PEITC, significantly increased GST and NQO1 activities in the rat liver. The only
      exception was the 30 d time point of feeding with raw cabbage juice. Cabbage
      juices, I3C and PEITC affected the hepatic GST MU to the greatest extent and GST
      alpha to a lesser extent. The results of the present study also showed that the
      treatment of rats with juices and compounds tested caused the translocation of
      the NF-E2-related transcription factor (Nrf2) active subunit from the cytosol to
      the nucleus, providing an argument for the involvement of this transcription
      factor in the induction of GST and NQO1. In contrast to the liver, cabbage juices
      affected only the renal GST theta, while treatment with I3C and PEITC
      significantly increased the activity of NQO1. Thus, the results of the present
      study indicate that induction of the key detoxifying enzymes by cabbage juices,
      particularly sauerkraut, may be responsible for their chemopreventive activity
      demonstrated by epidemiological studies and in animal models. However, the final
      effects might be organ or tissue dependent.

PMID- 21092380
TI  - Resynthesized lines and cultivars of Brassica napus L. provide sources of
      resistance to the cabbage stem weevil ( Ceutorhynchus pallidactylus (Mrsh.)).
AB  - The cabbage stem weevil (Ceutorhynchus pallidactylus (Mrsh.)) (Col.,
      Curculionidae) is a serious pest of winter oilseed rape (Brassica napus L. var.
      oleifera Metzg.) in central and northern Europe. Although host-plant resistance
      is a key tool in integrated pest management systems, resistant genotypes are not
      yet available for this species. Resynthesized rapeseed lines (B. oleracea L.*B.
      rapa L.) are broadening the genetic diversity and might have potential as sources
      of resistance to pest insects. The host quality, of nine resynthesized rapeseed
      lines and six genotypes of B. napus to cabbage stem weevil, was evaluated in
      laboratory screening tests and in a semi-field experiment. In dual-choice
      oviposition tests, female C. pallidactylus laid significantly fewer eggs on five
      resyntheses and on swede cv 'Devon Champion' than on the moderately susceptible
      oilseed rape cv 'Express', indicating a lower host quality of these genotypes.
      Results of laboratory screenings were confirmed in a semi-field experiment, in
      which twelve genotypes were exposed to C. pallidactylus females. The number of
      larvae was significantly lower in two resyntheses and in cv 'Devon Champion' than
      in oilseed rape cv WVB 9. The total, as well as individual, glucosinolate (GSL)
      content in the leaves differed substantially among the genotypes tested. The
      amount of feeding by larvae of C. pallidactylus, as measured by a stem-injury
      coefficient, was positively correlated with the indolyl GSL compounds 3
      indolylmethyl and 4-methoxy-3-indolylmethyl, and with the aromatic GSL 2
      phenylethyl, whereas it was negatively correlated with 4-hydroxy-3-indolylmethyl.
      Thus, the composition and concentration of GSL compounds within the plant tissue
      might be a key factor in breeding for pest resistance in oilseed rape.

PMID- 21092383
TI  - Food photographs in nutritional surveillance: errors in portion size estimation
      using drawings of bread and photographs of margarine and beverages consumption.
AB  - Food photographs are widely used as instruments to estimate portion sizes of
      consumed foods. Several food atlases are available, all developed to be used in a
      specific context and for a given study population. Frequently, food photographs
      are adopted for use in other studies with a different context or another study
      population. In the present study, errors in portion size estimation of bread,
      margarine on bread and beverages by two-dimensional models used in the context of
      a Belgian food consumption survey are investigated. A sample of 111 men and women
      (age 45-65 years) were invited for breakfast; two test groups were created. One
      group was asked to estimate portion sizes of consumed foods using photographs 1-2
      d after consumption, and a second group was asked the same after 4 d. Also, real
      time assessment of portion sizes using photographs was performed. At the group
      level, large overestimation of margarine, acceptable underestimation of bread and
      only small estimation errors for beverages were found. Women tended to have
      smaller estimation errors for bread and margarine compared with men, while the
      opposite was found for beverages. Surprisingly, no major difference in estimation
      error was found after 4 d compared with 1-2 d. Individual estimation errors were
      large for all foods. The results from the present study suggest that the use of
      food photographs for portion size estimation of bread and beverages is acceptable
      for use in nutrition surveys. For photographs of margarine on bread, further
      validation using smaller amounts corresponding to actual consumption is
      recommended.

PMID- 21092373
TI  - Neuropathological associates of multiple cognitive functions in two community
      based cohorts of older adults.
AB  - Studies of neuropathology-cognition associations are not common and have been
      limited by small sample sizes, long intervals between autopsy and cognitive
      testing, and lack of breadth of neuropathology and cognition variables. This
      study examined domain-specific effects of common neuropathologies on cognition
      using data (N = 652) from two large cohort studies of older adults. We first
      identified dimensions of a battery of 17 neuropsychological tests, and regional
      measures of Alzheimer's disease (AD) neuropathology. We then evaluated how
      cognitive factors were related to dimensions of AD and additional measures of
      cerebrovascular and Lewy Body disease, and also examined independent effects of
      brain weight. All cognitive domains had multiple neuropathology determinants that
      differed by domain. Neocortical neurofibrillary tangles were the strongest
      predictors of most domains, while medial temporal tangles showed a weaker
      relationship with episodic memory. Neuritic plaques had relatively strong effects
      on multiple domains. Lewy bodies and macroscopic infarcts were associated with
      all domains, while microscopic infarcts had more limited associations. Brain
      weight was related to all domains independent of specific neuropathologies.
      Results show that cognition is complexly determined by multiple disease
      substrates. Neuropathological variables and brain weight contributed
      approximately a third to half of the explained variance in different cognitive
      domains.

PMID- 21092384
TI  - Development of a dish-based, semi-quantitative FFQ for the Korean diet and cancer
      research using a database approach.
AB  - We used a database approach in developing a dish-based, semi-quantitative FFQ for
      Korean diet and cancer research. Cancer-related dietary factors (CRDF) recognised
      in the scientific community and dietary intake data from the 2001 Korean National
      Health and Nutrition Examination Survey and the 2002 Korean National Nutrition
      Survey by Season were used. The list of dishes (n 993) was those reported to be
      consumed by individuals over 30 years of age during all four seasons. The
      resulting 112-dish list was selected using contribution analyses and variability
      analyses to detect between-person variation for CRDF and non-CRDF nutrients.
      Variations of each dish were grouped into one dish for the final list of 112
      dishes, which were then linked to the nutrient database. The final 112 dish items
      consisted of nine Korean staple dishes, including rice and noodles, twenty-five
      soups and stews, fifty-four side dishes, nine beverages, nine fruit dishes and
      six alcoholic beverages. The percentage coverages of energy, protein, fat,
      carbohydrate and alcohol intake in the selected 112 dishes were 82.4, 76.4, 68.9,
      86.0 and 99.8 %, respectively. Dietary exposure to cancer-related Korean dietary
      factors can be assessed by this new dish-based, semi-quantitative FFQ. This new
      instrument can calculate the intake of CRDF along with non-CRDF nutrient intake
      for cancer research.

PMID- 21092385
TI  - Bipolar affective disorder, type II, apparently precipitated by donepezil.
AB  - There is considerable evidence that pro-cholinergic agents can cause depressed
      mood. However, there are also published case reports of a rare association
      between cholinesterase inhibitors and mood elevation in patients with pre
      existing major functional psychiatric disorders, or organic disorders other than
      dementia. This report adds to the literature by describing a case of mood
      elevation in a patient without pre-existing psychiatric disorder.

PMID- 21092391
TI  - Socio-economic aspects of neglected diseases: sleeping sickness and visceral
      leishmaniasis.
AB  - Several tropical diseases that are essentially poverty-related have recently
      gained more attention under the label of 'neglected tropical diseases' or NTD. It
      is estimated that over 1000 million people currently suffer from one or more NTD.
      Here, the socio-economic aspects of two NTD - human African trypanosomiasis and
      human visceral leishmaniasis - are reviewed. Both of these diseases affect the
      poorest of the poor in endemic countries, cause considerable direct and indirect
      costs (even though the national control programmes tend to provide free care) and
      push affected households deeper into poverty.

PMID- 21092389
TI  - Toward a better understanding of pig behavior and pig welfare.
AB  - Pork production began to flourish in the USA after the practice of finishing pigs
      on corn was popularized in the late 1600s. By the 1840s, there were 35 million
      pigs and 20 million people in the USA and Cincinnati was the world's largest pork
      market. Between 1890 and the present, the total number of pigs in the USA has
      remained at 50-60 million, but dramatic changes in swine husbandry over the
      course of the 20th century have metamorphosed pig production from small,
      extensive (outdoor), labor-dependent enterprises into large, intensive (indoor),
      capital-dependent, production systems. This development has led to debate
      concerning the impact of swine production on animal/human health, the
      environment, and the welfare of the animals under our care. In a very tangible
      way, the future of pork production depends on effectively addressing the public's
      concerns regarding animal welfare and health. Here, we review basic sensory and
      behavioral aspects of swine with the objective of reaching a better understanding
      of pig behavior and pig welfare. The premise of this discussion is that
      safeguarding animal welfare and health is good for pigs, pork producers and the
      animal-conscious public.

PMID- 21092387
TI  - Hippocampal atrophy relates to fluid intelligence decline in the elderly.
AB  - Measures of brain and hippocampal volume in 40 healthy young (aged 18-30 years)
      and 36 healthy elderly (aged 60-83 years) subjects were compared with composite
      cognitive function scores in three conceptual domains: memory ability, processing
      speed, and general fluid intelligence. Through a series of general linear models
      testing the relationship between these brain measures and cognitive performance
      scores, a significant positive relationship between hippocampal volume and fluid
      intelligence ability was found in elderly subjects but not in young. No
      relationship between the other cognitive domains and brain or hippocampal volume
      was found. The findings suggest a role of hippocampal atrophy in the decline in
      fluid intelligence in the elderly.

PMID- 21092388
TI  - Pre-dementia memory impairment is associated with white matter tract affection.
AB  - Mild cognitive impairment (MCI), especially amnestic, often represents pre
      dementia Alzheimer's disease, characterized by medial temporal lobe atrophy,
      while white matter (WM) alterations are insufficiently described. We analyze both
      cortical morphometric and WM diffusivity differences in amnestic versus non
      amnestic subtypes and ask if memory and WM tract affection are related
      independently of cortical atrophy. Forty-nine patients from a university-hospital
      based memory clinic with a score of 3 on the Global Deterioration Scale aged 43
      77 years (45% female) were included. Two neuropsychologists have classified cases
      as amnestic (aMCI), non-amnestic (naMCI), or less advanced (laMCI), not
      satisfying criteria for aMCI/naMCI. Diffusion tensor imaging (DTI) WM tract and
      morphometric data of the temporal-parietal memory network were compared among
      patient subtypes and related to story, word list, and visual memory. WM radial
      and mean diffusivity (DR and MD), underlying the entorhinal cortex, were higher
      in aMCI compared with laMCI. WM DR and MD, underlying the entorhinal,
      parahippocampal, and middle temporal cortex, explained unique variance in word
      list and story memory, and this was not due to secondary effects of cortical
      thinning. DTI may thus potentially aid diagnosis in early disease stages. ).

PMID- 21092390
TI  - Associations of dietary dark-green and deep-yellow vegetables and fruits with
      cervical intraepithelial neoplasia: modification by smoking.
AB  - Smoking has been positively and fruit and vegetable intake has been negatively
      associated with cervical cancer, the second most common cancer among women
      worldwide. However, a lower consumption of fruits and reduced serum carotenoids
      have been observed among smokers. It is not known whether the smoking effect on
      the risk of cervical neoplasia is modified by a low intake of fruits and
      vegetables. The present study examined the combined effects of tobacco smoking
      and diet using a validated FFQ and serum carotenoid and tocopherol levels on
      cervical intraepithelial neoplasia grade 3 (CIN3) risk in a hospital-based case
      control study conducted in Sao Paulo, Brazil, between 2003 and 2005. The sample
      comprised 231 incident, histologically confirmed cases of CIN3 and 453 controls.
      A low intake ( <= 39 g) of dark-green and deep-yellow vegetables and fruits
      without tobacco smoking had a lesser effect on CIN3 (OR 1.14; 95 % CI 0.49, 2.65)
      than among smokers with higher intake ( >= 40 g; OR 1.83; 95 % CI 0.73, 4.62)
      after adjusting for confounders. The OR for the joint exposure of tobacco smoking
      and low intake of vegetables and fruits was greater (3.86; 95 % CI 1.74, 8.57; P
      for trend < 0.001) compared with non-smokers with higher intake after adjusting
      for confounding variables and human papillomavirus status. Similar results were
      observed for total fruit, serum total carotene (including beta-, alpha- and gamma
      carotene) and tocopherols. These findings suggest that the effect of nutritional
      factors on CIN3 is modified by smoking.

PMID- 21092396
TI  - Chinius eunicegalatiae n. sp. (Diptera; Psychodidae), a cavernicolous sandfly
      from Laos.
AB  - A description is given of Chinius eunicegalatiae n. sp. (Diptera; Psychodidae)
      from Laos. This is the third known species belonging to the Asiatic genus Chinius
      Leng, 1987. Like C. junlianensis Leng, 1987 and C. barbazani Depaquit, Leger and
      Beales, 2006, C. eunicegalatiae n. sp. is a cavernicolous species. An absence of
      the R2 vein is shared with C. barbazani. A differential diagnosis with the two
      other known species of the genus is given. The main differential characters are
      the lengths of the genital filaments and of the spermathecal ducts.

PMID- 21092394
TI  - In areas of low transmission, is the presumptive treatment of febrile but
      bloodsmear-negative patients for malaria validated by the results of PCR-based
      testing?
AB  - Presumptive malaria treatment (PMT) is a common strategy in many areas of the
      world, especially in settings where the facilities for diagnosis are limited. The
      subjects of a recent study in central Sudan, in an area with a low level of
      Plasmodium falciparum transmission, were 322 individuals who had each presented
      at one of seven suburban health facilities, complaining of repeated febrile
      episodes. Although all were found bloodsmear-negative for malarial parasites, all
      were presumptively diagnosed as cases of malaria and prescribed artemisinin-based
      combination therapy. When pretreatment samples of blood were, however, checked
      for P. falciparum histidine-rich protein 2, using a rapid diagnostic test (RDT),
      and for Plasmodium DNA, using a PCR-based assay, only one (0.03%) of the cases
      was found RDT-positive and none was found PCR-positive. Although more studies are
      needed, in different areas and seasons, to see if these results mirror the
      general situation, it appears that the wide use of PMT in central Sudan, among
      patients who are bloodsmear-negative, is unjustified, of little, if any, benefit,
      and a waste of resources that are already limited. An international consortium
      for the revision of the conceptual aspects of malaria diagnosis and PMT is
      suggested.

PMID- 21092392
TI  - Emerging tropical diseases in Australia. Part 1. Leptospirosis.
AB  - Human leptospirosis is a zoonotic disease of global importance that causes
      significant morbidity and mortality, particularly in developing nations. In this
      review, the history, epidemiology, transmission, clinical presentation and
      treatment of this disease, and its impact in Australia, are discussed. Central to
      this review is the delineation of diagnostic methods for the disease and the
      challenges that this disease presents for both the clinician and diagnostic
      laboratory. This information should furnish clinicians with an updated tool to
      help overcome a number of problems associated with the diagnosis of
      leptospirosis.

PMID- 21092399
TI  - Ciliary hypertrichosis in a child with keratomalacia.

PMID- 21092393
TI  - Emerging tropical diseases in Australia. Part 2. Ciguatera fish poisoning.
AB  - Ciguatera poisoning is a food-borne neuro-intoxication caused by consumption of
      finfish that have accumulated ciguatoxins in their tissues. Ciguatera is a
      distressing and sometimes disabling condition that presents with a self-limiting
      though occasionally severe gastro-intestinal illness, progressing to a suite of
      aberrant sensory symptoms. Recovery can take from days to years; second and
      subsequent attacks may manifest in a more severe illness. Ciguatera remains
      largely a pan-tropical disease, although tourism and export fish markets
      facilitate increased presentation in temperate latitudes. While ciguatera
      poisoning in the South Pacific was recognised and eloquently described by
      seafarers in the 18th Century, it remains a public-health challenge in the 21st
      Century because there is neither a confirmatory diagnostic test nor a reliable,
      low-cost screening method to ascertain the safety of suspect fish prior to
      consumption. A specific antidote is not available, so treatment is largely
      supportive. The most promising pharmacotherapy of recent decades, intravenous
      mannitol, has experienced a relative decline in acceptance after a randomized,
      double-blind trial failed to confirm its efficacy. Some questions remain
      unanswered, however, and the use of mannitol for the treatment of acute ciguatera
      poisoning arguably deserves revisiting. The immunotoxicology of ciguatera is
      poorly understood, and some aspects of the epidemiology and symptomatology of
      ciguatera warrant further enquiry.

PMID- 21092386
TI  - Neuropsychological Profile of Parkin Mutation Carriers with and without Parkinson
      Disease: The CORE-PD Study.
AB  - The cognitive profile of early onset Parkinson's disease (EOPD) has not been
      clearly defined. Mutations in the parkin gene are the most common genetic risk
      factor for EOPD and may offer information about the neuropsychological pattern of
      performance in both symptomatic and asymptomatic mutation carriers. EOPD probands
      and their first-degree relatives who did not have Parkinson's disease (PD) were
      genotyped for mutations in the parkin gene and administered a comprehensive
      neuropsychological battery. Performance was compared between EOPD probands with
      (N = 43) and without (N = 52) parkin mutations. The same neuropsychological
      battery was administered to 217 first-degree relatives to assess
      neuropsychological function in individuals who carry parkin mutations but do not
      have PD. No significant differences in neuropsychological test performance were
      found between parkin carrier and noncarrier probands. Performance also did not
      differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes,
      compound heterozygotes/homozygotes). Similarly, no differences were found among
      unaffected family members across genotypes. Mean neuropsychological test
      performance was within normal range in all probands and relatives. Carriers of
      parkin mutations, whether or not they have PD, do not perform differently on
      neuropsychological measures as compared to noncarriers. The cognitive functioning
      of parkin carriers over time warrants further study.

PMID- 21092397
TI  - Large orbital hydatid cyst presenting as subconjunctival mass.

PMID- 21092398
TI  - A survey for intestinal parasites in a psychiatric institution in Sri Lanka.

PMID- 21092403
TI  - A meta-analysis for comparison of the two-layer and university of Wisconsin
      pancreas preservation methods in islet transplantation.
AB  - Conflicting results have been reported on the effectiveness of the two-layer
      method (TLM) compared with the University of Wisconsin (UW) method for preserving
      pancreata. The objective of this study was to compile the evidence for or against
      any difference in human islet yield and viability  between these two. PubMed
      (January 2000 to May 2008) and Cochran Library searches were performed and 17
      studies were included for the meta-analysis. Data on donor characteristics,
      preservation time, and outcomes were abstracted. Studies were subgrouped based on
      how TLM was used (UW + TLM or  TLM alone), on mean cold ischemic time (CIT) (>20
      h or <20 h), and on whether special chemical was used (yes or no). Meta-analysis
      of all studies and subgroups was performed and the pooled standardized mean
      differences (SMD) with 95% confidence intervals (CI) were reported. Overall,  the
      use of TLM significantly increased islet yield [SMD, 0.74 (0.44-1.04)] and
      viability [SMD, 0.63 (0.14-1.12)]. The beneficial effects of TLM on islet yield
      were more evident when TLM was used following UW storage or when prolonged CIT
      was used. TLM used alone, shorter CIT,  and no chemical use all resulted in
      similar islet viability between TLM and UW groups. Beneficial effects of TLM on
      islet viability were demonstrated only when TLM was used following UW storage, or
      with prolonged CIT, or with chemical use. In conclusion, the TLM was beneficial
      for prolonged  pancreas preservation before human islet isolation; however,
      benefit of the TLM for short-term preservation was not clear.

PMID- 21092395
TI  - Impact of intestinal helminthiases on the nutritional status of primary-school
      children in Osun state, south-western Nigeria.
AB  - In January-March 2000, the impact of intestinal helminthiases on the nutritional
      status of 749 pupils (353 boys and 396 girls) attending public primary schools in
      the Ife Central local government area of Osun state, in south-western Nigeria,
      was investigated. Demographic, socio-economic and other relevant information was
      collected on the pupils, on the same day that a single stool sample was collected
      from each subject and examined, using Stoll's dilution egg-count technique. The
      weights, heights and ages of the subjects were recorded and converted to
      percentages of the reference medians for weight-for-height, weight-for-age and
      height-for-age. The overall prevalences of helminth infection detected among the
      465 malnourished pupils (i.e. those with any form of under-nutrition) and the 284
      well-nourished pupils were 32.9% and 25.4%, respectively (P=0.029). The
      nutritional indices of the pupils who were found helminth-infected were generally
      lower than those of the pupils who appeared free of intestinal helminths. The
      mean values for weight-for-height, for example, were higher in the apparently
      uninfected pupils than in those found infected with any intestinal helminth
      (P=0.02) or only with Ascaris lumbricoides (P=0.05). Similarly, the mean height
      for-age of the pupils who were apparently uninfected was higher than the
      corresponding value for the pupils found hookworm-positive (P=0.003). The pupils
      who were each found infected with two or more species of intestinal infection had
      significantly lower weights-for-heights, weights-for-ages and heights-for-ages
      than the pupils who appeared to be helminth-free. The results of a multivariate
      logistic-regression analysis indicated that hookworm infection was a significant
      risk factor for underweight (P=0.015), wasting (P=0.033) and stunting (P=0.015)
      whereas Trichuris was only a significant risk factor for stunting (P=0.025). It
      appears that intestinal helminthiasis may play a causal or contributory role in
      the occurrence of childhood malnutrition, at least in the present study area.
      Steps should be taken to control both of these important health problems, through
      functional school-health programmes that provide regular deworming, supervised
      school meals and health education.

PMID- 21092402
TI  - Schwann cell coculture improves the therapeutic effect of bone marrow stromal
      cells on recovery in spinal cord-injured mice.
AB  - Studies of bone marrow stromal cells (MSCs) transplanted into the spinal cord
      injured rat give mixed results: some groups report improved locomotor recovery
      while others only demonstrate improved histological appearance of the lesion.
      These studies show no clear correlation between  neurological improvements and
      MSC survival. We examined whether MSC survival in the injured spinal cord could
      be enhanced by closely matching donor and recipient mice for genetic background
      and marker gene expression and whether exposure of MSCs to a neural environment
      (Schwann cells) prior  to transplantation would improve their survival or
      therapeutic effects. Mice underwent a clip compression spinal cord injury at the
      fourth thoracic level and cell transplantation 7 days later. Despite genetic
      matching of donors and recipients, MSC survival in the injured spinal cord was
      very  poor (~1%). However, we noted improved locomotor recovery accompanied by
      improved histopathological appearance of the lesion in mice receiving MSC grafts.
      These mice had more white and gray matter sparing, laminin expression, Schwann
      cell infiltration, and preservation of neurofilament  and 5-HT-positive fibers at
      and below the lesion. There was also decreased collagen and chondroitin sulphate
      proteoglycan deposition in the scar and macrophage activation in mice that
      received the MSC grafts. The Schwann cell cocultured MSCs had greater effects
      than untreated MSCs on all these  indices of recovery. Analyses of chemokine and
      cytokine expression revealed that MSC/Schwann cell cocultures produced far less
      MCP-1 and IL-6 than MSCs or Schwann cells cultured alone. Thus, transplanted MSCs
      may improve recovery in spinal cord-injured mice through immunosuppressive
      effects  that can be enhanced by a Schwann cell coculturing step. These results
      indicate that the temporary presence of MSCs in the injured cord is sufficient to
      alter the cascade of pathological events that normally occurs after spinal cord
      injury, generating a microenvironment that favors improved  recovery.

PMID- 21092405
TI  - Clinical potential of intravenous neural stem cell delivery for treatment of
      neuroinflammatory disease in mice?
AB  - While neural stem cells (NSCs) are widely expected to become a therapeutic agent
      for treatment of severe injuries to the central nervous system (CNS), currently
      there are only few detailed preclinical studies linking cell fate with
      experimental outcome. In this study, we aimed to validate whether IV
      administration of allogeneic NSC can improve experimental autoimmune
      encephalomyelitis (EAE), a well-established animal model for human multiple
      sclerosis (MS). For this, we cultured adherently growing luciferase-expressing
      NSCs (NSC-Luc), which displayed a uniform morphology and expression profile of
      membrane and intracellular markers, and which displayed an in vitro
      differentiation potential into neurons and astrocytes. Following labeling with
      green fluorescent micron-sized iron oxide particles (f-MPIO-labeled NSC-Luc) or
      lentiviral transduction with the enhanced green fluorescent protein (eGFP)
      reporter gene (NSC-Luc/eGFP), cell implantation experiments demonstrated the
      intrinsic survival capacity of adherently cultured NSC in the CNS of syngeneic
      mice, as analyzed by real-time bioluminescence imaging (BLI), magnetic resonance
      imaging (MRI), and histological analysis. Next, EAE was induced in C57BL/6 mice
      followed by IV administration of NSC-Luc/eGFP at day 7 postinduction with or
      without daily immunosuppressive therapy (cyclosporine A, CsA). During a follow-up
      period of 20 days, the observed clinical benefit could be attributed solely to
      CsA treatment. In addition, histological analysis demonstrated the absence of NSC
      Luc/eGFP at sites of neuroinflammation. In order to investigate the absence of
      therapeutic potential, BLI biodistribution analysis of IV-administered NSC
      Luc/eGFP revealed cell retention in lung capillaries as soon as 1-min
      postinjection, resulting in massive inflammation and apoptosis in lung tissue. In
      summary, we conclude that IV administration of NSCs currently has limited or no
      therapeutic potential for neuroinflammatory disease in mice, and presumably also
      for human MS. However, given the fact that grafted NSCs have an intrinsic
      survival capacity in the CNS, their therapeutic exploitation should be further
      investigated, and-in contrast to several other reports-will most likely be highly
      complex.

PMID- 21092406
TI  - Platelet lysate consisting of a natural repair proteome supports human
      mesenchymal stem cell proliferation and chromosomal stability.
AB  - With favorable regenerative and immunotolerant profiles, patient-derived human
      mesenchymal stem cells (hMSCs) are increasingly considered in cell therapy.
      Derived from bone marrow (BM) and standardized with culture in fetal bovine serum
      (FBS), translation of hMSC-based approaches is impeded by protracted expansion
      times, risk of xenogenic response, and exposure to zoonoses. Here, human platelet
      lysate adherent to good manufacturing practices (GMP-hPL) provided a nonzoonotic
      adjuvant that enhanced the capacity of BM-hMSC to proliferate. The nurturing
      benefit of GMP-hPL was generalized to hMSC from adipose tissue evaluated as an
      alternative to bone marrow. Long-term culture in GMP-hPL maintained the
      multipotency of hMSC, while protecting against clonal chromosomal instability
      detected in the FBS milieu. Proteomic dissection identified TGF-beta, VEGF, PDGF,
      FGF, and EGF as highly ranked effectors of hPL activity, revealing a paradigm of
      healing that underlies platelet lysate adjuvancy. Thus, GMP-adherent human
      platelet lysate accelerates hMSC proliferation with no chromosomal aberrancy,
      through an innate repair paradigm.

PMID- 21092404
TI  - Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into
      sheep fetuses.
AB  - Long-term engraftment and phenotype correction has been difficult to achieve in
      humans after in utero stem cell transplantation mainly because of allogeneic
      rejection. Autologous cells could be obtained during gestation from the amniotic
      fluid with minimal risk for the fetus and the  mother. Using a sheep model, we
      explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs)
      for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF)
      under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9,
      58 days of  gestation, term = 145 days). AFMSCs were isolated and expanded in all
      sampled fetal sheep. Those cells were transduced using an HIV vector encoding
      enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%)
      transduction efficiency rate. After expansion, transduced AFMSCs  were injected
      into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound
      guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal
      injection was successful in the remaining 7 fetal sheep giving a 78% survival for
      the full procedure. Tissues were sampled  at postmortem examination 2 weeks
      later. PCR analysis detected GFP-positive cells in fetal tissues including liver,
      heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein
      was detected in these tissues by Western blotting and further confirmed by
      cytofluorimetric  and immunofluorescence analyses. This is the first
      demonstration of autologous stem cell transplantation in the fetus using AFMSCs.
      Autologous cells derived from AF showed widespread organ migration and could
      offer an alternative way to ameliorate prenatal congenital disease.

PMID- 21092407
TI  - The presence of apoptotic bone marrow cells impairs the efficacy of cardiac cell
      therapy.
AB  - Injection of autologous bone marrow cells into infarcted myocardium has been
      proposed to limit the deterioration of cardiac function following myocardial
      infarction (MI); unfortunately, the beneficial effects observed have been modest.
      One of the limiting factors is believed to be poor  local survival of the
      injected cells, but the potential impact of apoptosis among the injected cells
      has yet to be assessed. Therefore, this study aimed to quantify the apoptosis
      rate in bone marrow mononuclear cells (BMMCs) prepared for cardiac therapy, and
      to analyze their effects in vitro  on cardiomyoblast apoptosis and in vivo on
      cardiac function recovery following MI. Using rabbit BMMCs prepared by Ficoll
      gradient, apoptotic cells were detected via Annexin V (AnV) staining. The effects
      of depleting the apoptotic cell population by means of AnV magnetic beads was
      tested in  vitro after coculture with cardiomyoblasts (H9c2 cells) and in vivo
      after cell injection into the infarcted area. Left ventricular ejection fraction
      and scar extent were assessed by echography and histology 2 months later. After
      Ficoll gradient isolation, 37.3% (33.4-37.9%) of BMMCs  were found to be
      apoptotic (Apo(Base) BMMCs). AnV depletion decreased the proportion of apoptotic
      cells to 20% (17.6-32%) (Apo(Low) BMMCs). Rabbits treated in vivo with Apo(Low)
      BMMCs after MI presented with significantly improved left ventricular ejection 
      fraction [41.4% (41.0-43.6%) vs. 34.6% (34.6-35.9%), p = 0.03), reduced scar
      extent [20.4% (17.9-24.3%) vs. 25.6% (17.9-27.9%), p = 0.057], and reduced rate
      of cardiomyocyte apoptosis compared to those treated with Apo(Base) BMMCs. H9c2
      apoptosis  was found to be higher after coculture with Apo(Base) than with
      Apo(Low) BMMCs [25.6% (22.6-29.6%) vs. 10.1% (6.6-12.6%), p = 0.03], a result
      partially reproduced by cocultures with microparticle-rich supernatants from
      BMMCs. The presence of apoptotic  cells among BMMCs impairs the efficacy of
      cardiac cell therapy after MI, an effect possibly mediated by apoptotic
      microparticles.

PMID- 21092408
TI  - Human amnion epithelial cells prevent bleomycin-induced lung injury and preserve
      lung function.
AB  - Human amnion epithelial cells (hAECs) have attracted recent attention as a
      promising source of cells for regenerative therapies, with reports that cells
      derived from human term amnion possess multipotent differentiation ability, low
      immunogenicity, and anti-inflammatory properties. Specifically, in animal models
      of lung disease characterized by significant loss of lung tissue secondary to
      chronic inflammation and fibrosis, the transplantation of hAECs has been shown to
      reduce both inflammation and subsequent fibrosis. To further explore the
      mechanisms by which hAECs reduce pulmonary fibrosis and enhance lung
      regeneration, we utilized a bleomycin-induced model of pulmonary fibrosis and
      investigated the ability of hAECs to reduce fibrosis and thereby improve
      pulmonary function. We aimed to determine if hAECs, injected into the peritoneal
      cavity could migrate to the lung, engraft, and form functional lung epithelium,
      and whether hAECs could modulate the inflammatory environment in the bleomycin
      injured lung. We demonstrated that, compared to bleomycin alone, IP
      administration of hAECs 24 h after bleomcyin, decreased gene expression of the
      proinflammatory cytokines TNF-alpha, TGF-beta, IFN-gamma, and IL-6 and decreased
      subsequent pulmonary fibrosis with less pulmonary collagen deposition, reduced
      levels of alpha-smooth muscle actin and decreased inflammatory cell infiltrate.
      We also showed that hAECs are able to prevent a decline in pulmonary function
      associated with bleomycin-induced lung damage. We were unable to detect any
      significant engraftment of hAECs in injured, or uninjured, lung after
      administration. The findings from this study support the further investigation of
      hAECs as a potential cell therapy for inflammatory and fibrogenic diseases.

PMID- 21092410
TI  - NUP98-HOXA10hd-expanded hematopoietic stem cells efficiently reconstitute bone
      marrow of mismatched recipients and induce tolerance.
AB  - Gene therapy as well as methods capable of returning cells to a pluripotent state
      (iPS) have enabled the correction of genetic deficiencies in syngenic adult
      progenitors, reducing the need for immunosuppression in cell therapy approaches.
      However, in diseases involving mutations that  lead to the complete lack of a
      protein, such as Duchenne muscular dystrophy, the main immunogens leading to
      rejection of transplanted cells are the therapeutic proteins themselves. In these
      cases even iPS cells would not circumvent the need for immunosuppression, and
      alternative strategies  must be developed. One such potential strategy seeks to
      induce immune tolerance using hematopoietic stem cells originated from the same
      donor or iPS line from which the therapeutic progenitors are derived. However,
      donor hematopoietic stem cells (HSCs) are available in limiting numbers and 
      embryonic stem (ES) cell-derived HSCs engraft poorly in adults. While these
      limitations have been circumvented by ectopic expression of HOXB4, overexpression
      of this protein is associated with inefficient lymphoid reconstitution. Here we
      show that adult HSCs expanded with a NUP98- HOXA10hd  fusion protein sustain long
      term engraftment in immunologically mismatched recipients and generate normal
      numbers of lymphoid cells. In addition, NUP98-HOXA10hd-expanded cells induce
      functional immune tolerance to a subsequent transplant of myogenic progenitors
      immunologically matched with  the transplanted HSCs.

PMID- 21092411
TI  - Bioreactor for the long-term culture of lung tissue.
AB  - In this article we describe the design and validation of a bioreactor for the in
      vitro culture of whole rodent lung tissue. Many current systems only enable large
      segments of lung tissue to be studied ex vivo for up to a few hours in the
      laboratory. This limitation restricts the study  of pulmonary biology in
      controlled laboratory settings, and also impacts the ability to reliably culture
      engineered lung tissues in the laboratory. Therefore, we designed, built, and
      validated a bioreactor intended to provide sufficient nutrient supply and
      mechanical stimulation to support  cell survival and differentiation in cultured
      lung tissue. We also studied the effects of perfusion and ventilation on
      pulmonary cell survival and maintenance of cell differentiation state. The final
      bioreactor design described herein is capable of supporting the culture of whole
      native lung  tissue for up to 1 week in the laboratory, and offers promise in the
      study of pulmonary biology and the development of engineered lung tissues in the
      laboratory.

PMID- 21092409
TI  - Striatal stimulation nurtures endogenous neurogenesis and angiogenesis in chronic
      phase ischemic stroke rats.
AB  - Deep brain stimulation (DBS) is used to treat a variety of neurological disorders
      including Parkinson's disease. In this study, we explored the effects of striatal
      stimulation (SS) in a rat model of chronic-phase ischemic stroke. The stimulation
      electrode was implanted into the ischemic  penumbra at 1 month after middle
      cerebral artery occlusion (MCAO) and thereafter continuously delivered SS over a
      period of 1 week. Rats were evaluated behaviorally coupled with neuroradiological
      assessment of the infarct volumes using magnetic resonance imaging (MRI) at pre-
      and post-SS.  The rats with SS showed significant behavioral recovery in the
      spontaneous activity and limb placement test compared to those without SS. MRI
      visualized that SS also significantly reduced the infarct volumes compared to
      that at pre-SS or without SS. Immunohistochemical analyses revealed a  robust
      neurogenic response in rats that received SS characterized by a stream of
      proliferating cells from the subventricular zone migrating to and subsequently
      differentiating into neurons in the ischemic penumbra, which exhibited a
      significant GDNF upregulation. In tandem with this SS-mediated  neurogenesis,
      enhanced angiogenesis was also recognized as revealed by a significant increase
      in VEGF levels in the penumbra. These results provide evidence that SS affords
      neurorestoration at the chronic phase of stroke by stimulating endogenous
      neurogenesis and angiogenesis.

PMID- 21092412
TI  - Use of a clinically approved iron oxide MRI contrast agent to label human
      hepatocytes.
AB  - Reliable noninvasive methods are needed to monitor cell engraftment and graft
      survival after hepatocyte transplantation. Superparamagnetic iron oxide
      nanoparticles (SPIOs) have been shown to accumulate in various types of cells,
      and are currently the labeling agent of choice for cellular magnetic resonance
      imaging (MRI). However, for successful clinical translation to hepatocyte
      transplantation, it is important that hepatocytes maintain their viability and
      synthetic function after labeling. In this study, primary human hepatocytes were
      incubated with increasing concentrations of clinical grade SPIOs for different
      time intervals. SPIOs uptake was confirmed by light and fluorescence microscopy,
      and intracellular iron content quantified by a colorimetric ferrozine-based
      assay. Studies were performed to determine if labeling affected cell viability
      and function. Intracellular iron concentrations increased in a time- and dose
      dependent manner after incubation with SPIOs. Labeling had minimal short-term
      effects on cell attachment and mitochondrial function. However, exposure of
      hepatocytes to SPIOs resulted in a dose- and time-dependent reduction in protein
      synthesis. Cell labeling for 16 h had no significant effect on hepatocyte
      specific function, but longer periods of incubation resulted in a dose-dependent
      decrease in albumin production. Hepatocytes incorporated SPIOs at sufficient
      levels for in vitro detection on a 7-T MRI imaging system, with a minimum of
      2,000 SPIO-labeled cells/MUl detected by a decreased T2 relaxivity compared to
      controls. Intrasplenic transplantation of human hepatocytes labeled with 50 MUg
      Fe/ml of SPIOs was performed in nonobese diabetic/severe combined immune
      deficiency (NOD-Scid) mice. Recipient livers showed a clear decrease in signal
      intensity on T2*-weighted MR images when compared to controls, allowing detection
      of hepatocytes. With further experiments to optimize the conditions for labeling
      human hepatocytes, it should be possible to apply this technique to track
      hepatocyte transplantation in patients with liver disease.

PMID- 21092415
TI  - Supports used for positioning of patients in hip arthroplasty: is there an
      infection risk?
AB  - INTRODUCTION: Infection after joint arthroplasty is a disastrous complication.
      Implants used in hip arthroplasty increase the risk of infection from organisms
      of low pathogenicity. Potential reservoirs, that have not been assessed as yet,
      are the supports used for patient positioning in hip arthroplasty. The purpose of
      this study was to assess these supports for presence of bacterial pathogens.
      SUBJECTS AND METHODS: We studied 40 supports used in 20 hip arthroplasty
      procedures. Tryptone soya agar plates were used to sample these supports. All
      agar plates were incubated at 37  degrees C for 48 h. RESULTS: Of the 20 anterior
      supports, 17 (85%) showed bacterial colonisation; of the 20 posterior supports,
      10 (50%) had bacterial colonisation. Fourteen (52%) supports were contaminated
      with one organism, 9 (33%) with two organisms, three (11%) with three organisms
      and one (4%) with four organisms. Coagulase-negative staphylococci were the most
      common isolated organisms (61%) followed by coryneforms (10%) and bacilli (10%).
      Anterior supports had two times more colony forming units compared to the
      posterior supports. CONCLUSIONS: This study showed contamination of supports used
      for positioning patients during hip arthroplasty. It reflects poor cleaning
      practice and certainly raises the possibility that a high bacterial load on these
      supports may contribute to higher infection rates in hip arthroplasties. The
      study raises concerns related to contamination of supports, as there is a
      potential for cross-infection, wound problems, and deep sepsis around implants
      which could be disastrous. While colonisation does not equate with infection, we
      suggest thorough cleaning of the supports before and after every surgical
      procedure.

PMID- 21092413
TI  - Effect of splenectomy on pancytopenia after a peripheral blood stem cell
      transplantation.
AB  - To analyze the effect of a splenectomy on pancytopenia after a peripheral blood
      stem cell transplantation (PBSCT) in chronic myeloid leukemia (CML) patients.
      Three CML patients diagnosed with splenomegaly in our department from 2002 to
      2006 received a splenectomy after PBSCT. Patient  1, a 42-year-old male in
      chronic phase (CP), received an HLA-identical sibling allo-PBSCT. Patient 2, a 28
      year-old female in aggressive phase (AP), received a PBSCT from her twin. Patient
      3, a 26-year-old male in chronic phase (CP), received a PBSCT from an unrelated
      donor. The conditioning  regimen included busulfan and cyclophosphamide (BU/CY2).
      Patients 1, 2, and 3 received splenectomies on days 168, 51, and 114,
      respectively. Bcr-abl transcripts were detected using the polymerase chain
      reaction (PCR). Chimerism was documented by PCR amplification of a variable
      number of tandem  repeat (VNTR) polymorphrisms. Neither metrisone (2 mg/kg/day
      for 7 days), mycophenolic acid (MMF) (0.5 g twice daily for 1 month), high-dose
      gamma-globulin (0.4 g/kg/day for 5 days), granulocyte colony-stimulating factor
      (G-CSF) therapy, nor erythropoietin (EPO) therapy had produced post-PBSCT 
      hematopoiesis recovery. Patients 1 and 2 had 5% Ph-positive chromosomes while
      patient 3 exhibited graft-versus-host disease (GVHD). After receiving the
      splenectomy, all three had a rapid hematopoeitic recovery with no evidence of Ph
      positive chromosomes, and patients 1 and 3 showed complete  donor chimerism
      (CDC). Patient 1 developed chronic GVHD (cGVHD) on day 210 postsplenectomy that
      was treated successfully with prednisone. Patient 2 had acute GVHD on day 55 that
      was treated successfully with dexamethasone (10 mg), administered intravenously
      once a day for 3 days with good  clinical response. To date, patients 1, 2, and 3
      have survived postprocedure for 85, 49, and 25 months, respectively. Splenectomy
      is an effective option for the patients who have pancytopenia after PBSCT and the
      patients recovered a good graft function after splenectomy without procedure
      related  complication and with long-time survival. GVHD can develop in both allo
      PBSCT and syngeneic PBSCT. A splenectomy after PBSCT may increase the risk of
      GVHD, enhance the effect of graft versus leukemia (GVL), promote CDC formation.

PMID- 21092414
TI  - Mesenchymal stem cells in renal function recovery after acute kidney injury: use
      of a differentiating agent in a rat model.
AB  - Acute kidney injury (AKI) is a major health care condition with limited current
      treatment options. Within this context, stem cells may provide a clinical
      approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan
      monoesters with butyric acid (HB), able to induce  metanephric differentiation,
      formation of capillary-like structures, and secretion of angiogenic cytokines,
      was tested in vitro. Thereafter, we investigated the effects of human mesenchymal
      stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB,
      after induction of ischemic  AKI in a rat model. At reperfusion following 45-min
      clamping of renal pedicles, each rat was randomly assigned to one of four groups:
      CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed.
      Histological samples were analyzed by light and electron microscopy and renal 
      injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs
      induced an accelerated renal functional recovery, demonstrated by biochemical
      parameters and confirmed by histology showing that histopathological alterations
      associated with ischemic injury were less severe in cell-treated  kidneys. HB
      treated rats showed a minor degree of inflammation, both at cytokine and TEM
      analyses. Better functional and morphological recovery were not associated to
      stem cells' regenerative processes, but possibly suggest paracrine effects on
      microenvironment that induce retrieval of renal  damaged tissues. These results
      suggest that FMhMSCs could be useful in the treatment of AKI and the utilization
      of synthetic compounds could enhance the recovery induction ability of cells.

PMID- 21092417
TI  - Chemical-physical characterization of polyurethane catheters modified with a
      novel antithrombin-heparin covalent complex.
AB  - Detailed structural studies were made of polyurethane catheter surfaces modified
      with a covalent antithrombin-heparin (ATH) complex that has superior
      anticoagulant activity compared to unfractionated heparin. ATH was grafted onto
      polyurethane catheters by surface film preparation involving a three-step
      process: (1) activation of ATH through functionalized poly(ethylene glycol)
      (PEG), (2) base-coating treatment of the polyurethane surface and (3) final
      attachment of ATH onto the surface by free radical polymerization. With the
      application of base coating, composed of polyhydroxyethylmethacrylates and
      poly(ethylene oxide) (PEO), the coating process could easily be transferred to
      other biomaterials by adjusting the base-coating composition. Anti-factor Xa
      assays confirmed high anticoagulant activity of the ATH coatings. To determine
      structural aspects critical for biological function, the product was analyzed
      using differential scanning calorimetry and SDS-PAGE. Radiolabeled ATH was used
      to determine the graft density, homogeneity and stability of modified surfaces,
      as well as the competition of PEO-ATH migration to the surface with self
      aggregation of the PEO-ATH molecules during the coating process. X-ray
      photoelectron spectroscopy was used to investigate the surface chemical
      composition before and after ATH application. Analysis showed that PEO-ATH was
      strongly surface-bound at a final density of 15-200 pmol/cm(2), depending on the
      incubation concentration. 

PMID- 21092416
TI  - Pre-operative cardiac workup after anthracycline-based neoadjuvant chemotherapy.
      Is it really necessary?
AB  - INTRODUCTION: In patients receiving pre-operative anthracyclines for locally
      advanced breast cancer, early cardiotoxicity is a well-recognised complication
      that may interfere with surgery. The aim of this study was to assess the safety
      of breast surgery after neoadjuvant treatment with  Doxorubicin. PATIENTS AND
      METHODS: A retrospective study of breast cancer patients treated with Doxorubicin
      as part of their neoadjuvant protocol. All patients were subsequently operated in
      our institution. Intra-operative and postoperative haemodynamic, cardiac or
      respiratory events were  collected. RESULTS: A total of 83 patients were
      included. All patients had a normal left ventricular ejection fraction before
      starting on chemotherapy. Doxorubicin was given in conjunction with
      Cyclophosphamide and Paclitaxel. The cumulative dose of Doxorubicin was 240
      mg/m(2).  All patients completed their chemotherapy less than a year before
      surgery and were clinically asymptomatic. Of the patients, 2.3% displayed a
      significant reduction in cardiac function to meet cardiotoxicity criteria,
      although not clinically apparent. No complications occurred intra-operatively  or
      postoperatively. CONCLUSIONS: Breast surgery can be safely performed after breast
      neoadjuvant chemotherapy with Doxorubicin. The risk of early cardiotoxicity does
      not mandate a cardiac function assessment after completion of treatment. Work-up
      should be individualised according to the  anthracycline regimen, patient's
      cardiac risk factors and functional status before surgery.

PMID- 21092418
TI  - Formation of concentric multilayers in a chitosan hydrogel inspired by Liesegang
      ring phenomena.
AB  - Liesegang rings, periodical bands or ring patterns formed by inorganic
      precipitation in polymer gel medium, have attracted lots of interest of
      researchers aiming to construct ordered structures. Inspired by the Liesegang
      ring phenomena, chitosan, instead of inorganic species, was used as building
      block to construct a chitosan hydrogel with concentric multilayers in a
      protonated chitosan/NaOH reaction system by alternate soaking in NaOH solution
      and water. The morphology of concentric multilayers structure was characterized
      by environmental scanning electron microscopy. The upload and release behavior of
      isoniazid was also investigated. The quantitive rules of the concentric layer
      position/the square root of reaction time and the position of the consecutive
      concentric layer coincide with the time law and space law of the classical
      Liesegang ring phenomena, respectively. The chitosan solution converts into a
      hydrogel accompanied by remarkable volume shrinkage due to hydrogen bonds
      reconstruction and electrostatic repulsion disappearance. The separated
      concentric multilayers can be formed due to the fluctuation of hydroxide ions
      concentration when the neutralization is interrupted by alternate soaking in NaOH
      solution and water. The major difference of the concentric multilayers in
      chitosan hydrogel from the classical Liesegang ring phenomena occurring in
      inorganic precipitation systems is that chitosan not only plays the role of
      reactant in chitosan hydrogel formation, but also acts as supporting reaction
      medium to control the diffusion behavior of hydroxide ions. The porosity and
      equilibrium swelling ratio of the chitosan xerogel are 63% and 1100%,
      respectively, which is feasible for drug uploading through diffusion or
      absorption. The isoniazid release kinetics are dominated by the diffusion-erosion
      model. The chitosan hydrogel with concentric multilayers structure loaded with
      isoniazid will have wide applications in treatment of bone tuberculosis. 

PMID- 21092421
TI  - Poly(acrylic acid)-grafted poly(N-isopropyl acrylamide) networks: preparation,
      characterization and hydrogel behavior.
AB  - Poly(acrylic acid)-grafted poly(N-isopropylacrylamide) co-polymer networks
      (PNIPAAm-g-PAA) were prepared via the reversible addition-fragmentation transfer
      (RAFT) polymerization of N-isopropyl- acrylamide (NIPAAm) with trithiocarbonate
      terminated PAA as a macromolecular chain-transfer agent in the presence of N,N
      methylenebisacrylamide. The PNIPAAm-g-PAA co-polymer networks were characterized
      by means of Fourier transform infrared spectroscopy, differential scanning
      calorimetry and small-angle X-ray scattering. It is found that the PNIPAAm-g-PAA
      co-polymer networks were microphase-separated, in which the microdomains of
      PNIPAAm-PAA interpolymer complexes were dispersed into the PNIPAAm matrix. The
      PNIPAAm-g-PAA hydrogels displayed a dual response to temperature and pH values.
      The thermoresponsive properties of PNIPAAm-g-PAA networks were investigated.
      Below the volume phase transition temperatures, the PNIPAAm-g-PAA hydrogels
      possessed much higher swelling ratios than control PNIPAAm hydrogel. In terms of
      swelling, deswelling and reswelling tests, it is judged that the PNIPAAm-g-PAA
      hydrogels displayed faster response to the external temperature changes than
      control PNIPAAm hydrogel. The improved thermoresponsive properties of hydrogels
      are ascribed to the formation of PAA-grafted PNIPAAm networks, in which the water
      soluble PAA chains behave as the hydrophiphilic tunnels and allow water molecules
      to go through and, thus, to accelerate the diffusion of water molecules. 

PMID- 21092419
TI  - Porous silk fibroin film as a transparent carrier for cultivated corneal
      epithelial sheets.
AB  - Biological carriers, such as the amniotic membrane and serum-derived fibrin, are
      currently used to deliver cultivated corneal epithelial sheets to the ocular
      surface. Such carriers require being transparent and allowing the diffusion of
      metabolites in order to maintain a healthy ocular surface. However, safety issues
      concerning biological agents encouraged the development of safer, biocompatible
      materials as cell carriers. We examined the application of porous silk fibroin
      films with high molecular permeability prepared by mixing silk fibroin and
      poly(ethylene glycol) (PEG), and then removal of PEG from the silk-PEG films.
      Molecular permeability of porous silk fibroin film is higher than untreated silk
      fibroin film. Epithelial cells were isolated from rabbit limbal epithelium, and
      seeded onto silk fibroin coated wells and co-cultured with mitomycin C-treated
      3T3 fibroblasts. Stratified epithelial sheets successfully engineered on porous
      silk fibroin film expressed the cornea-specific cytokeratins K3 and K12, as well
      as the corneal epithelial marker pax6. Basement membrane components such as type
      IV collagen and integrin beta1 were expressed in the stratified epithelial
      sheets. Further more, colony-forming efficiency of dissociated cells was similar
      to primary corneal epithelial cells showing that progenitor cells were preserved.
      The biocompatibility of fibroin films was confirmed in rabbit corneas for up to 6
      months. Porous silk fibroin film is a highly transparent, biocompatible material
      that may be useful as a carrier of cultivated epithelial sheets in the
      regeneration of corneal epithelium. 

PMID- 21092422
TI  - Performance of protein-A-based affinity membranes for antibody purification.
AB  - The preparation of affinity membranes for application in antibody purification
      studies is described here. Protein-A-attached poly(hydroxyethyl methacrylate-N
      methacryloyl-L-alanine) (PHEMAAL) membranes were produced by a
      photopolymerization technique and then characterized by swelling tests, surface
      area measurements, contact angle and scanning electron microscopy (SEM) studies.
      The water swelling ratio of the PHEMAAL membrane was 133.2%. PHEMAAL membranes
      have large pores with a size in the range of 5-10 MUm. Protein A was covalently
      attached onto the PHEMAAL membranes via cyanogen bromide (CNBr) activation.
      Maximum protein A loading was 4.7 mg/g. There was a very low non-specific IgG
      adsorption onto the PHEMAAL membranes, about 0.38 mg/g. The maximum IgG
      adsorption on the PHEMAAL-protein A membrane was found to be 9.8 mg/g at pH 7.4
      from aqueous solutions. Higher adsorption amount was observed from human plasma
      (up to 37.3 mg/g). Adsorbed IgG was eluted using 0.1 M glycine-HCl buffer (pH
      3.5) with a purity of 93%. PHEMAAL-protein A membrane was used for repetitive
      adsorption/elution of IgG without noticeable loss in IgG adsorption amount after
      10 cycles. The PHEMAAL-protein A membrane showed several advantages, such as
      simpler preparation procedure, good selectivity for IgG purification from human
      plasma and good stability throughout repeated adsorption-elution cycles. 

PMID- 21092427
TI  - Of surgeons and safety checklists.

PMID- 21092424
TI  - Synthesis and characterization of thermo-sensitive radio-opaque poly(N
      isopropylacrylamide-co-PEG-2-iodobenzoate).
AB  - Radiopacity is required for embolic materials to be monitored by angiography
      during embolization. Covalently bound radio-opaque biomaterials would be ideal
      for embolization. Poly(N-isopropylacrylamide-co-PEG-acrylate) modified with 2
      iodobenzoyl chloride was synthesized and characterized by (1)H-NMR, differential
      scanning calorimetry and X-ray opacity. Poly(N-isopropylacrylamide-co-PEG-2
      iodobenzoate) shows radiopacity, as well as thermo-sensitivity. Cytotoxicity
      testing on these co-polymers shows little cytotoxicity. Phase-transition
      temperature and radiopacity varied according to the content of NIPAAm and 2
      iodobenzoate. Increasing the content of 2-iodobenzoate raised the radiopacity and
      lowered the LCST. 

PMID- 21092426
TI  - Novel approach for chronic wound treatment by autologous transplantation.

PMID- 21092423
TI  - Inhibition of microbial growth by silver-starch nanocomposite thin films.
AB  - A sago starch biopolymer with embedded silver nanoparticles has been studied as a
      material for the prevention of microbial growth. Approximately 8 nm in size,
      silver nanoparticles have been synthesized by reduction of the silver salt in
      aqueous solution in the presence of sago starch using sodium borohydride as a
      reducing agent. The obtained solutions were cast on glass plates to obtain thin
      supported silver-starch nanocomposite films. The morphology of the nanocomposites
      was investigated by scanning and transmission electron microscopy. UV-Vis
      absorption spectroscopy showed that during the film formation a part of the
      silver nanoparticles has been trapped in the water present in the sample, which
      enabled their partial oxidation into active Ag(+) species. The oxidation of the
      silver nanoparticles was confirmed by X-ray photoelectron spectroscopy. The
      antimicrobial activity tests have shown that the nanocomposite material can be
      successfully employed to prevent the viability and growth of the common pathogens
      Staphylococcus aureus, Escherichia coli and Candida albicans. 

PMID- 21092432
TI  - Management of primary rectal cancer by surgeons in Atlantic Canada: results of a
      regional survey.
AB  - BACKGROUND: We sought to determine the current practice patterns of general
      surgeons in Atlantic Canada in the management of primary rectal cancer in
      relation to surgeon-specific variables. METHODS: We sent mail-out surveys to all
      practising general surgeons (n = 183) in Atlantic Canada to determine screening
      preferences, preoperative assessment, the use of neoadjuvant and adjuvant
      therapy, surgical therapy for rectal cancer and surgeon demographics. We analyzed
      the responses using chi(2) tests. RESULTS: The response rate was 98 (54%) after 2
      mail-outs; there were 82 (49%) eligible responses. Surgeons in practice for 21
      years or more were more likely than those with fewer than 21 years of practice to
      order preoperative ultrasonography of the liver and were less likely to order
      preoperative computed tomography. Endorectal ultrasonography was ordered
      routinely by 23% of surgeons, whereas 71% of surgeons would order it if time and
      resources were available. Surgeons who were not certified by the Royal College of
      Physicians and Surgeons of Canada were significantly more likely than those who
      were certified to use neoadjuvant therapy in all patients with rectal cancer (43%
      v. 12%; p = 0.031). Surgeons who performed more than 10 rectal cancer surgeries
      per year were significantly more likely than those who performed 10 or fewer
      surgeries per year to use neoadjuvant treatment for T3 tumours (94% v. 61%; p =
      0.007). Surgeons with medical or radiation oncology services in their communities
      were significantly more likely than those without such services to recommend
      neoadjuvant treatment in T3 rectal tumours and rectal tumours with pathologic
      lymph nodes. CONCLUSION: We found significant variation in the management of
      rectal cancer depending on surgeon-specific variables. The implications of these
      differences on the outcomes of patients with rectal cancer are unknown.

PMID- 21092429
TI  - Rural patients' experiences accessing surgery in British Columbia.
AB  - BACKGROUND: More than 33% of Canadians live in rural areas. The vulnerability of
      rural surgical patients makes them particularly sensitive to barriers to
      accessing health care. This study aims to describe rural patients' experiences
      accessing local nonspecialist, family physician-surgeon care and regional
      specialist surgical care when no local surgical care was available. METHODS: We
      conducted a qualitative pilot study of self-selected patients. Interviews were
      analyzed using a modified Delphi technique and NVivo qualitative software.
      RESULTS: The needs of rural surgical patients were reflective of Maslow's
      hierarchy of needs: physiologic, safety and security, community belonging and
      self-esteem/self-actualization. Rural patients expressed a strong desire for
      individualized care in a familiar environment. When such care was not available,
      patients found it difficult to meet even basic physiologic needs. Maternity
      patients and marginalized populations were particularly vulnerable. CONCLUSION:
      Rural patients seem to prefer individualized care in a familiar environment to
      address more of their qualitative emotional, psychological and cultural needs
      rather than only the physiologic needs of surgery. Larger studies are needed to
      delineate more clearly the qualitative aspects of surgical care.

PMID- 21092436
TI  - Practical tips for surgical research. Ensuring balanced groups in surgical
      trials.

PMID- 21092430
TI  - Clinical outcomes of midclavicular fractures treated with titanium elastic nails.
AB  - BACKGROUND: Midclavicular fractures are common clinically, accounting for about
      76% of all clavicular fractures. Recent studies have revealed a previously
      unrecognized incidence of nonunion and malunion after conservative treatment of
      more severe midclavicular fractures. Our aim was to evaluate the clinical
      outcomes of midclavicular fractures treated with titanium elastic nails. METHODS:
      From February 2005 to February 2007, 41 patients with displaced midclavicular
      fractures received open reduction and internal fixation with a titanium elastic
      nail inserted through the sternal end of the clavicle. We evaluated the visual
      analogue scale (VAS), the Constant score and the Disabilities of the Arm,
      Shoulder and Hand (DASH) scale to determine outcomes. RESULTS: A mean follow-up
      of 14.5 months (range 7-24 mo) revealed radiographic fracture union in all
      patients with an average clinical healing time of 2.2 months. Mean subjective
      pain 3 days after surgery was significantly lower than the day before surgery (p
      < 0.001). The mean range of motion 3 days after surgery was significantly
      improved compared with the day before surgery (p < 0.001). The nails were removed
      in all patients a mean of 7.2 months (range 5.4-9.5 mo) after surgery, and no
      fractures recurred. The mean postoperative DASH score was 2.5 (range 0.5-8.0) and
      the mean postoperative Constant score was 95.2 (range 86.5-97.0). CONCLUSION:
      Limited open reduction and internal fixation with titanium elastic nails is a
      safe and minimally invasive surgical procedure for the treatment of displaced
      midclavicular fractures in adults and achieves good functional results and high
      patient satisfaction.

PMID- 21092438
TI  - [Update on definition, diagnosis and classification of chronic kidney disease].

PMID- 21092428
TI  - Adherence to perioperative antibiotic prophylaxis among orthopedic trauma
      patients.
AB  - BACKGROUND: The goal of this study was to assess whether patients receive their
      antibiotic prophylaxis as prescribed. We also investigated what doses and
      durations of antibiotics are typically ordered, which patients actually receive
      antibiotics and factors causing the ordered antibiotic regimen to be altered.
      METHODS: We performed a retrospective review of 205 patient charts and sent a
      national survey to all surgeon members of the Canadian Orthopaedic Trauma Society
      (COTS) about antibiotic prophylaxis in the setting of surgical treatment for
      closed fractures. RESULTS: In all, 93% (179 of 193) of patients received an
      appropriate preoperative dose of antibiotics, whereas less than 32% (58 of 181)
      of patients received their postoperative antibiotics as ordered. The most
      commonly stated reason for patients not receiving their postoperative antibiotics
      as ordered was patients being discharged before completing 3 postoperative doses.
      There was a 70% (39 of 56) response rate to the survey sent to COTS surgeons. A
      single dose of a first-generation cephalosporin preoperatively followed by 3
      doses postoperatively is the most common practice among orthopedic trauma
      surgeons across Canada, but several surgeons give only preoperative prophylaxis.
      CONCLUSION: Adherence to multidose postoperative antibiotic regimens is poor.
      Meta-analyses have failed to demonstrate the superiority of multidose regimens
      over single-dose prophylaxis. Single-dose preoperative antibiotic prophylaxis may
      be a reasonable choice for most orthopedic trauma patients with closed fractures.

PMID- 21092431
TI  - Preoperative bowel preparation for patients undergoing elective colorectal
      surgery: a clinical practice guideline endorsed by the Canadian Society of Colon
      and Rectal Surgeons.
AB  - BACKGROUND: Despite evidence that mechanical bowel preparation (MBP) does not
      reduce the rate of postoperative complications, many surgeons still use MBP
      before surgery. We sought to appraise and synthesize the available evidence
      regarding preoperative bowel preparation in patients undergoing elective
      colorectal surgery. METHODS: We searched MEDLINE, EMBASE and Cochrane Databases
      to identify randomized controlled trials (RCTs) comparing patients who received a
      bowel preparation with those who did not. Two authors reviewed the abstracts to
      identify articles for critical appraisal. We used the methods of the United
      States Preventive Services Task Force to grade study quality and level of
      evidence, as well as formulate the final recommendations. Outcomes assessed
      included postoperative infectious complications, such as anastomotic dehiscence
      and superficial surgical site infections. RESULTS: Our review identified 14 RCTs
      and 8 meta-analyses. Based on the quality and content of these original
      manuscripts, we formulated 6 recommendations for various aspects of bowel
      preparation in patients undergoing elective colorectal surgery. CONCLUSION:
      Taking into account the lack of difference in postoperative infectious
      complication rates when MBP is omitted and the adverse effects of MBP, we believe
      that, based on the literature, MBP before surgery should be omitted.

PMID- 21092439
TI  - [Colorectal cancer screening:methods/models and the strategies based on the
      present policies in China].

PMID- 21092433
TI  - Selective use of magnetic resonance cholangiopancreatography in clinical practice
      may miss choledocholithiasis in gallstone pancreatitis.
AB  - BACKGROUND: Gallstone pancreatitis is a consequence of ampullary obstruction by
      common bile duct (CBD) calculi. Magnetic resonance cholangiopancreatography
      (MRCP) has been advocated for routine use to diagnose choledocholithiasis.
      However, the selective use of MRCP in clinically equivocal situations has not
      been explored until now. This study examines the diagnostic value of selective
      MRCP in gallstone pancreatitis. METHODS: We conducted a retrospective audit of
      all presentations of gallstone pancreatitis between January 2001 and December
      2007 at Middlemore Hospital, Auckland, New Zealand. Demographic data, clinical
      presentation, biochemical and radiological findings and outcomes were reviewed.
      RESULTS: There were 339 cases of gallstone pancreatitis during the study period;
      236 patients were women and the mean age was 52 years. Overall,
      choledocholithiasis was diagnosed in 95 patients. A total of 117 patients
      underwent MRCP within a median of 4 days of admission, with 15 (13.7%) showing
      choledocholithiasis. There was no significant difference in time to MRCP between
      positive and negative groups. Endoscopic retrograde cholangiopancreatography
      (ERCP)/intraoperative cholangiography (IOC) confirmed 13 of 15 stones within a
      median of 2.5 days. However, MRCP missed 8 cases of choledocholithiasis
      subsequently demonstrated on ERCP/IOC, where clinical suspicion remained after a
      negative MRCP. Its sensitivity was 62% and specificity 98%. The positive
      likelihood ratio was 6.5 and the negative likelihood ratio was 0.1. In all, 222
      patients followed different clinical pathways with 82 CBD stones diagnosed by
      ERCP/IOC. CONCLUSION: Selective MRCP is highly specific in gallstone pancreatitis
      but may not be sensitive enough to exclude choledocholithiasis in this context.

PMID- 21092437
TI  - Case series. Soft-tissue sarcoma of the foot.
AB  - BACKGROUND: We reviewed cases of soft-tissue sarcoma of the foot to gain insight
      into the presentation, treatments and outcomes for this rare disease and to
      determine whether limb-salvage surgery yields reasonable functional and
      oncological outcomes. METHODS: We reviewed the cases of 16 patients treated by 2
      of us (R.T. and M.I.) for soft-tissue sarcoma of the foot over a 15-year period.
      We extracted the following information from each patient's medical record:
      disease status at presentation, prior treatment, histological diagnosis, American
      Joint Committee on Cancer (AJCC) stage, details of treatment, oncological outcome
      and functional outcome. Functional outcome was assessed with the Toronto
      Extremity Salvage Score (TESS) and the Musculoskeletal Tumor Society (MSTS 1987).
      RESULTS: Follow-up averaged 6 (range 2-15) years. Eight patients presented after
      unplanned excision. Histological diagnosis was synovial sarcoma for 7 of 16
      patients.The tumours were evenly distributed among the hindfoot, midfoot and
      forefoot. Most patients (n = 13) presented with AJCC stage II or III disease.
      Amputation was necessary for 3 patients, whereas limb salvage was possible for
      the other 13. Free tissue transfer (n = 9) and radiation therapy (n = 12) were
      used in most cases. Surgical margins were microscopically positive in 4 of the 13
      patients treated with limb salvage.Local disease recurred in 2 patients. Lung
      metastases occurred in 4 patients. At last follow-up, 11 of 16 patients were
      alive without disease, 2 with disease and 3 had died of their disease. Functional
      assessment with MSTS 1987 and the TESS averaged 28%and 90%, respectively, after
      limb salvage. CONCLUSION: In this series, we found that, first, patients
      frequently presented after unplanned excision, and this may have led to worse
      oncological outcomes compared with patients who presented primarily. Second, limb
      salvage was usually possible, but it required accepting marginal resections,
      relying on free tissue transfer to obtain coverage and using radiation therapy to
      obtain local control. Third, this combination yielded an acceptable local control
      rate and very good functional outcomes.

PMID- 21092434
TI  - Prospective clinical and radiographic results of CHARITE III artificial total
      disc arthroplasty at 2- to 7-year follow-up: a Canadian experience.
AB  - BACKGROUND: Early and intermediate results have shown that the SB CHARITE III
      total disc arthroplasty (TDA) favourably compares to spinal fusion, but is
      associated with fewer complications and higher levels of satisfaction. We sought
      to prospectively report the clinical and radiographic results of the CHARITE III
      TDA after an average of 55 months follow-up. METHODS: We conducted a prospective
      study of patients receiving the CHARITE TDA at either L4-5 or L5-S1 between April
      2001 and November 2006. The primary indication for surgery was discogenic low
      back pain confirmed by provocative discography. Assessment included pre- and
      postoperative (3, 6 and 12 mo and yearly thereafter) validated patient outcome
      measures and radiographic review. RESULTS: Fifty-seven of the potential 64 (89%)
      patients were available for complete follow-up. Their mean age was 39 (range 21
      59) years. A statistically significant improvement was demonstrated between all
      the mean pre- and postoperative intervals for the Oswestry Disability Index,
      visual analogue scale for back and leg pain, and Short Form-36 health survey (p <
      0.001). The mean sagittal rotation was 6.5 degrees  (range 0.5 degrees -22.4
      degrees ), and the mean intervertebral translation was 1.1 mm (range 0-2.4 mm).
      Subsidence of the implant was present in 44 of 53 (83%) patients with an L5-S1
      disc arthroplasty. The mean subsidence was 1.7 mm (range 0-4.8 mm). CONCLUSION:
      The 2- to 7-year follow-up of this cohort of patients demonstrated satisfactory
      clinical and radiographic results in a carefully selected patient population. The
      radiographic assessment confirmed preservation and maintenance of motion at the
      replaced disc during the period of follow-up.

PMID- 21092435
TI  - CAGS and ACS evidence based reviews in surgery. 35: Efficacy and safety of low
      dose hydrocortisone therapy in the treatment of septic shock.
AB  - OBJECTIVE: To evaluate the efficacy and safety of low-dose hydrocortisone therapy
      in patients with septic shock. DESIGN: Multicentre, randomized, double-blind,
      placebo-controlled trial. SETTING: Nine centres (including 52 intensive care
      units) in Europe and the Middle East. PATIENTS: Patients with clinical evidence
      of infection, evidence of systemic response to infection and onset of shock
      within the previous 72 hours (defined by systolic blood pressure < 90 mm Hg
      despite adequate fluid replacement or a need for vasopressors for at least 1
      hour) and hypoperfusion or organ dysfunction attributable to sepsis.
      INTERVENTION: INTERVENTION group (n = 251) was randomly assigned to receive 50 mg
      of hydrocortisone intravenously, and the control group (n = 248) was randomly
      assigned to receive placebo every 6 hours for 5 days; the dose was tapered during
      a 6-day period. MAIN OUTCOME MEASURE: Death at 28 days in patients who did not
      have a response to corticotrophin. RESULTS: In all, 233 (46.7%) patients did not
      have a response to corticotrophin (125 in the treatment group and 108 in the
      placebo group). At 28 days, there was no significant difference in mortality
      between patients in the 2 groups who did not have a response to corticotropin
      (39.2% in the treatment group and 36.1% in the placebo group, p = 0.69) or
      between those who had a response to corticotropin (28.8% in the treatment group
      and 28.7% in the placebo group, p = 1.00). At 28 days, 86 of 251 (34.3%) patients
      in the treatment group and 78 of 248 (31.5%) in the placebo group had died (p =
      0.51). In the treatment group, shock was reversed more quickly than in the
      placebo group. However, there were more episodes of superinfection, including new
      sepsis and septic shock. CONCLUSION: Hydrocortisone cannot be recommended as
      general adjuvant therapy for septic shock (vasopressor responsive), nor can
      corticotrophin testing be recommended to determine which patients should receive
      hydrocortisone therapy.

PMID- 21092443
TI  - [The diagnosis of Crohn's disease of the small bowel: comparing CT enterography,
      capsule endoscopy, small-bowel follow through and ileocolonoscopy].
AB  - OBJECTIVE: To investigate the diagnostic value of capsule endoscopy (CE), CT
      enterography (CTE), ileocolonoscopy and small bowel follow through (SBFT) for
      small bowel Crohn's disease (CD). METHODS: Fifty-seven consecutive patients with
      CD underwent ileocolonoscopy, CTE, CE, and SBFT. It included the presence of the
      following symptoms and signs: abdominal pain, weight loss, diarrhea, fever and
      positive fecal occult blood test. The location and the characteristics of
      intestinal and extra-intestinal lesions detected by four techniques were
      compared. The proportions of patients with positive findings using each
      examination were compared. RESULTS: Of the 57 patients, 50 underwent
      ileocolonoscopy, terminal ileum lesion was found in 33 patients (66.00%), the
      remaining 17 (34.0%) were normal; among 34 patients who had CTE, 29 of small
      bowel lesion were found (85.29%); CE were performed in 27 patients, due to
      prolonged gastric transit one time, the capsule did not reach the cecum in one
      patient during battery lifetime. CE showed small bowel lesion in 26 patients
      (96.30%); SBFT was performed in 39 patients and 26 of small bowel lesion were
      detected (66.67%). CE had the highest diagnostic yield for CD and ileocolonoscopy
      had the lowest, and there were statistically significant difference among the 4
      examinations (P = 0.006). The combined positive rates of two methods were: CE +
      CTE 92.86% (13/14), SBFT + CTE 90.91% (20/22), CE + ileocolonoscopy 95.65%
      (22/23), CE + SBFT 100% (17/17), ileocolonoscopy + CTE 89.66% (26/29),
      ileocolonoscopy + SBFT 77.78% (28/36), but there were no significant differences
      between each two examinations. CONCLUSION: CE, CTE have a higher yield in
      depicting mild to moderate finding of CD than SBFT. CE is better for assessing
      early mucosal disease, whereas CTE is better for detecting transmural and
      extraluminal abnormalities. Most important, CE plus CTE may depict nonobstructive
      CD of the small bowel when conventional techniques such as ileocolonoscopy or
      SBFT have negative or inconclusive finding. CE provides us explanations for the
      symptoms of patients, decision to follow up or therapy.

PMID- 21092442
TI  - [A multicenter, double-blind, placebo-controlled, randomized, phase III clinical
      study of etanercept in treatment of ankylosing spondylitis].
AB  - OBJECTIVE: To evaluate the short-term efficacy and safety of etanercept treatment
      in Chinese patients with active ankylosing spondylitis (AS). METHODS: This was a
      12-week multicenter, double-blind, placebo-controlled, randomized phase III
      clinical study. The first part was a 6-week placebo-controlled period followed by
      a 6-week open-label period. The primary efficacy endpoint was the percentage of
      subjects achieving a 20% improvement in assessment in ankylosing spondylitis
      (ASAS) (ASAS 20). The secondary efficacy endpoints were the percentage of
      patients achieving a 40% improvement in ASAS (ASAS 40), achieving a 50%
      improvement in ASAS (ASAS 50), achieving a 70% improvement in ASAS (ASAS 70), and
      ASAS 5/6 responses at all visits, and the improvement in subject global
      assessment, physician global assessment, nocturnal and total back pain, bath AS
      functional index (BASFI), bath AS disease activity index (BASDAI), spinal
      mobility, joint assessment and quality of life assessment. All subjects in the
      study were evaluated for safety. RESULTS: The primary endpoint, ASAS 20 at week
      6, was achieved by 86.5% (64/74) patients in the etanercept group compared to
      29.5% (23/78) patients in the placebo group (P < 0.001). As early as week 2, the
      percentages of patients achieving the ASAS 20 between the two groups were
      significantly different. Furthermore, the majority of secondary efficacy end
      points were also significantly improved. Most of adverse events (AE) were mild in
      nature, the commonest adverse events were elevated liver function levels,
      injection site reactions and nasopharyngitis. No death or serious AE were
      observed. CONCLUSION: Etanercept can improve symptoms fastly, significantly and
      safely in Chinese patients with active AS.

PMID- 21092440
TI  - [To modify the design of preclinical trials: a lesson from the failure of
      neuroprotection trials in stroke].

PMID- 21092441
TI  - [An antimicrobial resistance surveillance of gram-positive cocci isolated from 12
      teaching hospitals in China in 2009].
AB  - OBJECTIVE: To investigate antimicrobial resistance among gram-positive cocci in
      China in 2009. METHODS: From June to December 2009, 1169 consecutive and non
      repetitive gram-positive cocci were collected from 12 teaching hospitals at 9
      cities. The minimal inhibitory concentration (MIC) of antibacterial agents was
      determined by agar dilution method. RESULTS: The prevalences of methicillin
      resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase
      negative Staphylococci (MRCoNS) were 45.3% (211/466) and 89.5% (214/239),
      respectively. The isolation rate of MRSA was 33.3% - 68.1% from different
      samples. All Staphylococci isolates were susceptible to vancomycin, teicoplanin
      and linezolid. Five point five percent (7/128) E.faecium strains were resistant
      to vancomycin. All E. faecalis strains were susceptible to vancomycin. About
      99.1% (108/109) of E.faecalis and E.faecium were susceptible to linezolid. The
      prevalence of penicillin-intermediate Streptococcus pneumoniae (PISP) was 21.6%
      (48/222). Only 1 (0.5%, 1/222) Streptococcus pneumoniae strain was resistant to
      penicillin. Teicoplanin, vancomycin, linezolid and tigecycline were the most
      active agents against Streptococcus pneumoniae (susceptible rate 100%).
      CONCLUSIONS: The high prevalence of methicillin-resistance is among
      Staphylococcus strains. Different samples show a different MRSA prevalence.
      Teicoplanin, vancomycin and linezolid show very high activity to Staphylococci,
      E. faecalis, E. faecium and Streptococcus pneumoniae.

PMID- 21092445
TI  - [The clinical characteristics and prognosis of non ST segment elevation acute
      coronary syndrome in different genders].
AB  - OBJECTIVE: To determine gender differences in baseline characteristics and
      intervention treatment in relation to prognosis in patients with non-ST segment
      elevation acute coronary syndrome (NSTEACS). METHODS: A total of 814 patients
      (545 men and 269 women) with NSTEACS were randomized to early intervention
      (coronary angiography < 24 hours after randomization) or delayed intervention
      (coronary angiography > 36 hours after randomization). The primary outcome was a
      composite of death, myocardial infarction, or stroke at 6 months. RESULTS: Women
      were older and more frequently had hypertension, diabetes, and history of
      coronary artery disease (CAD) or chronic angina (P < 0.05 for all). Women less
      were smokers and had elevations in cardiac marker (P < 0.05 for both). Women who
      underwent angiography had no significant lesions more often, but the left main
      stem and/or three-vessel diseases were similar with men. In adjusted multiple
      logistic regression analysis, the previous myocardial infarction and severe
      coronary artery disease were independently associated with the risk of primary
      endpoint in women. On multivariate analysis for men, severe coronary artery
      disease delayed intervention strategy and at least 3 risk factors for CAD were
      independently associated with the risk of primary endpoint. CONCLUSIONS: In
      NSTEACS patients, different gender had the different prognostic predictor. Severe
      coronary diseases were as an independent predictor for both male and female
      patients. An early intervention strategy resulted in a beneficial effect in men
      which was not seen in women.

PMID- 21092444
TI  - [The clinical features, neuroimaging findings and pathological characteristics of
      26 patients with pathologically proven tumor-like inflammatory demyelinating
      diseases].
AB  - OBJECTIVE: To summarize the clinical features, neuroimaging findings and
      pathological characteristics of 26 patients with tumor-like inflammatory
      demyelinating diseases (TIDD) confirmed by histopathology for better diagnosis
      and differential diagnosis. METHODS: The clinical features, neuroimaging findings
      and pathological characteristics of 26 patients (14 male, 12 female) with
      pathologically proven TIDD (24 brain-type and 2 spinal cord-type) were
      retrospectively analysed. RESULTS: The mean onset age was 6 - 69 (36.7 +/- 13.8)
      years. Twenty-one patients had good prognosis with a median followed-up duration
      of 51.0 months. Two patients were died of post-operative complication and
      pulmonary infection respectively and the remaining 3 patients were lost to
      followed up. The TIDD patients almost showed monophasic clinical setting.
      Headache, indifference accompanied with hypothesis were the commonest initial
      symptoms. The positive or abnormal rates of cerebrospinal fluid oligoclonal bands
      (OCB) and myelin basic protein (MBP) in TIDD patients were high. The involvements
      of bilateral and multi-lesions were commonest in TIDD (61.5%, 65.4%
      respectively). Twenty-two patients with CT unenhanced scanning showed hypodense
      lesions. Long T(1) and long T(2) signal intensity was showed on MRI and most
      cases appeared round-like lesion in shape. According to the shape of enhancement
      of the 23 patients performed with contrast agents, 11 were shown with open-ring
      enhancement, 4 cases (including 2 accompanied with open-ring enhancement) with
      complete ring enhancement, 3 with asymmetrical dotted enhancement, 2 with
      diffused even enhancement, and no enhancement was seen in the other 6.
      Furthermore, 14 cases with DWI and 12 with FLAIR all appeared hyperdensity. The
      typical pathological changes were demyelinating, perivascular inflammatory cells
      infiltration and reactive gliosis. Occasionally, the Creutzfeldt cells were also
      found in brain tissue of some patients. CONCLUSIONS: TIDD is a distinct
      demyelinating disease entity. In spite of being apt to be confused with the
      neoplasm in brain and spinal cord. TIDD has its own-features, for example, OCB is
      frequently positive in patients with TIDD and the level of MBP may be
      significantly increased. Furthermore, the involvements of bilateral and multi
      lesions are the common in TIDD, and most cases showed open-ring enhancement or
      complete rim enhancement on MRI. In addition, all cases present hypodense lesions
      on unenhanced CT and patients with hyperdense seemed not to be considered as
      TIDD.

PMID- 21092446
TI  - [A clinical analysis of 25 cases of prosthetic valve endocarditis].
AB  - OBJECTIVE: To report the clinical characteristics of prosthetic valve
      endocarditis (PVE). METHODS: All 25 cases of definite PVE (Duke criteria)
      diagnosed at our hospital between January 1992 to December 2008 were
      retrospectively analyzed. Among them, 7 cases were pathologically confirmed and
      the others were clinically confirmed with either 2 major criteria or 1 major and
      >= 3 minor criteria. Their clinical characteristics, underlying heart diseases,
      previous heart operations, presenting manifestations, causative microbes,
      echocardiographic findings and prognosis, were studied. RESULTS: (1) Although
      most cases underwent valve transplantations for underlying heart diseases of
      rheumatic heart diseases and congenital heart diseases, 10 patients were
      complicated with infectious endocarditis (IE) prior to the operations, 4 of them
      were PVE. (2) Eleven of them developed PVE within 2 months postoperatively. Fever
      (100%), major vessel embolism (48%), and anemia (36%) were the most frequently
      manifestations. Fourteen cases (56%) had positive culture results with 15
      causative pathogens, including 5 coagulase-negative Staphylococcus (CNS, 3 were
      methicillin-resistant coagulase-negative Staphylococcus, MRSCoN), 4 fungi, 2
      Enterococcus faecalis, 2 Burkholderia cepacia, 1 Stenotrophomonas maltophilia,
      and 1 Streptococcus. (3) Prosthetic valve vegetations, periannular leakage,
      regurgitation, were the main echocardiographic findings. Transesophageal
      echocardiography (TEE) revealed 13 PVE who had no positive findings on previous
      transthoracic echocardiography (TTE). (4) Eighteen PVE (72%) developed peri
      annular complications (12 leakage, 3 dehiscence, 2 abscesses, 1 fistula), major
      vessel embolism, congestive heart failure (16%) were frequently observed, 9 of
      the 17 patients died in hospital, in spite of intensive managements. CONCLUSIONS:
      PVE has a high mortality and is a severe complication for patients who underwent
      heart surgery. Its causative pathogen spectrum is quite different from that of
      native valve endocarditis. TTE is not sensitive for some PVE cases.

PMID- 21092447
TI  - [The efficacy and safety of PAD and VAD regimens for untreated multiple myeloma].
AB  - OBJECTIVE: To compare the efficacy and adverse effects of bortezomib + adriamycin
      + dexamethasone (PAD) and vincristine + adriamycin + dexamethasone (VAD) regimens
      in untreated multiple myeloma (MM). METHODS: There were 26 and 28 new diagnosed
      MM patients in PAD and VAD groups. Both clinical effects and adverse effects were
      observed. Patients accepted VAD or PAD regimens for 2 - 4 cycles and followed up
      for 7 - 27 months. RESULTS: There were 10, 5 and 11 patients accepted 2, 3 and 4
      cycles in PAD group, and 6, 11 and 11 in VAD group. In PAD group, there were 2,
      14, 9, 1 and 0 patients achieved complete remission (CR), very good partial
      remission (VGPR), partial remission (PR), stable disease (SD) and progressive
      disease (PD); in VAD group, the number were 0, 4, 12, 10 and 2. The rate of
      patients who achieved good efficacy (CR + VGPR) in PAD group was 61.5%, which was
      higher than that in VAD group (14.3%). The incidences of infection and
      gastrointestinal symptoms were similar in the two groups, while the incidences of
      peripheral neuropathy, thrombosis and Herpes Zoster infection in PAD group were
      higher than those in VAD group. CONCLUSIONS: Compared with the conventional VAD
      chemotherapy, PAD may improve CR and VGPR rates in new diagnosed MM, while it may
      bring more and severer toxicities in peripheral neuropathy, thrombosis and Herpes
      Zoster infection. Preventive medical care is necessary in PAD protocol.

PMID- 21092448
TI  - [The clinical significance of immune-related marker detection in idiopathic
      thrombocytopenic purpura].
AB  - OBJECTIVE: To assess the clinical significance of detecting the immune markers in
      idiopathic thrombocytopenic purpura (ITP). METHODS: The frequencies of
      circulating B cells secreting platelet-specific antibody, platelet-specific
      antibody, the percentage of T lymphocyte subsets, the percentage of reticulated
      platelet and the level of thrombopoietin in 64 ITP patients and 31 healthy
      controls were measured with enzyme-linked immunospot assay (ELISPOT), modified
      monoclonal antibody immobilization of platelet antigens assay (MAIPA), flow
      cytometry and sandwich enzyme-linked immunosorbent assay respectively. RESULTS:
      Compared with the controls [1.3 +/- 0.5/10(5) peripheral blood mononuclear cell
      (PBMC), (0.33 +/- 0.06, 0.41 +/- 0.03), (22.08 +/- 4.54)% and (8.19 +/- 2.46)%],
      the frequencies of circulating B cells secreting platelet-specific antibody (7.6
      +/- 4.6/10(5) PBMC in acute ITP group, 5.3 +/- 3.0/10(5) PBMC in chronic ITP
      group), platelet-specific antibody (including the anti-GPIIb/IIIa antibody, anti
      GPIb/IX antibody) (0.51 +/- 0.11, 0.48 +/- 0.06 in acute ITP group; 0.49 +/-
      0.10, 0.46 +/- 0.09 in chronic ITP group), the percentage of CD(8)(+) T
      Lymphocyte (27.09 +/- 9.86)%, the percentage of reticulated platelet in ITP
      patients [the megakaryocyte cytosis group (24.85 +/- 19.18)%, the normal
      megakaryocyte group (23.89 +/- 18.90)%] were significantly increased (all P <
      0.05). The frequencies of circulating B cells secreting platelet-specific
      antibody in acute ITP patients were notably increased (P < 0.05) compared to the
      chronic ITP patients. In T lymphocyte subsets, the percentage of CD(3)(+) T
      lymphocyte and CD(4)(+) T lymphocyte and the ratio of CD(4)(+)/CD(8)(+) in the
      patients with ITP [(60.88 +/- 14.59)%, (28.41 +/- 10.55)%, 1.18 +/- 0.59] were
      notably decreased than those in the healthy controls [(69.89 +/- 6.43)%, (35.38
      +/- 5.05)%, 1.64 +/- 0.29, P < 0.05]. There was no apparent difference of the
      level of thrombopoietin between ITP patients with megakaryocyte cytosis (72.09 +/
      41.64) and health controls (75.37 +/- 26.32, P > 0.05), however, the level of
      thrombopoietin of ITP patients with normal megakaryocyte apparently increased
      (118.60 +/- 70.72, P < 0.05). CONCLUSION: Detecting the frequencies of
      circulating B cells secreting platelet-specific antibody, platelet-specific
      antibody, the percentage of T lymphocyte subsets, the percentage of reticulated
      platelet and the level of thrombopoietin in the patients with ITP may improve the
      diagnosis and guide clinical therapy.

PMID- 21092449
TI  - [The significance of methylation status of secreted frizzled-related protein gene
      promoter in acute leukemia].
AB  - OBJECTIVE: To investigate the relationship between promoter hypermethylation of
      secreted frizzled-related protein (SFRP) gene and acute leukemia (AL). METHODS:
      We examined the promoter methylation status of SFRP1, 2, 4 and 5 in primary or
      relapsed AL patients, cell lines (HL60, NB4, Molt-4 and Jurkat) and peripheral
      blood mononuclear cells from healthy people with methylation-specific PCR (MSP).
      RESULTS: None of the normal mononuclear cells showed methylation of any SFRP
      genes. The frequencies of aberrant methylation among the samples were 33.9%
      (20/59) for SFRP1, 23.7% (14/59) for SFRP2, 6.8% (4/59) for SFRP4 and 10.2%
      (6/59) for SFRP5 in acute myelocytic leukemia (AML), and 39.3% (11/28) for SFRP1,
      28.6% (8/28) for SFRP2, 25.0% (7/28) for SFRP4 and 32.1% (9/28) for SFRP5 in
      acute lymphoblastic leukemia (ALL). Hypermethylation of SFRP1, 2, 5 genes were
      present in the 4 AL cell lines. SFRP4 was methylated in NB4, Molt-4 and Jurkat
      cell lines. However, methylation and unmethylation of SFRP4 were both detected in
      HL60. CONCLUSIONS: Hypermethylation of SFRP genes is a common event in the
      evolution of AL. Methylation of SFRP genes might serve as potential independent
      biomarkers for early detection of AL.

PMID- 21092450
TI  - [The expression of CD73 in CD4+ regulatory T cells in patients with new-onset
      systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the level of CD(73) expression in CD(4)(+) regulatory T
      (Treg) cells in patients with systemic lupus erythematosus (SLE) and explore its
      role in the pathogenesis of SLE. METHODS: We selected 29 untreated/active SLE
      patients and 22 healthy controls. Frequencies of CD(4)(+)CD(25)(+) CD(73)(+) T
      cells and levels of FOXP3 protein expressed in CD(4)(+)CD(73)(+),
      CD(4)(+)CD(25)(hi), CD(4)(+)CD(25)(+) T cells were analyzed by flow cytometry.
      Meanwhile, the levels of SLE disease activity index (SLEDAI), C reactive protein
      (CRP), ESR, immunoglobulin and complement were measured. RESULTS: The percent of
      CD(4)(+)CD(25)(+) CD(73)(+) T cells was decreased in new-onset SLE compared with
      healthy controls [(1.25 +/- 1.32)% vs (2.35 +/- 1.09)%, P < 0.01], and it had no
      correlation with the levels of SLEDAI, CRP, ESR, et al and anti-C(1q) and anti
      nucleosome antibodies (P > 0.05 for each). Both in groups of new-onset SLE and
      healthy controls, CD(73) level expressed in CD(4)(+)CD(25)(hi) T cells [(29.05 +/
      12.53)%, (43.35 +/- 10.09)%] was higher than that expressed in CD(4)(+)CD(25)(+)
      T cells [(17.48 +/- 6.92)%, (29.98 +/- 10.39)%, P < 0.01]. In both SLE patients
      and healthy controls, levels of FOXP3 protein expressed in CD(4)(+)CD(73)(+) T
      cells [(65.36 +/- 14.40)%, (63.80 +/- 14.05)%] and CD(4)(+)CD(25)(hi) T cells
      [(67.30 +/- 13.04)%, (56.30 +/- 9.21)%] were higher than those in
      CD(4)(+)CD(25)(+) T cells [(45.70 +/- 12.74)%, (43.98 +/- 5.17)%, P < 0.001],
      while it had no significant difference between the CD(4)(+)CD(25)(hi) and
      CD(4)(+)CD(73)(+) T cells (P > 0.05). CONCLUSION: These results demonstrate that
      CD(73) may be a new surface marker of regulatory T cells, and the abnormal
      expression of CD(73) in Treg cells may participate in the pathogenesis of SLE.

PMID- 21092451
TI  - [The influence of indomethacin on TNFalpha and skeletal muscle protein catabolism
      in chronic obstructive pulmonary disease rat model].
AB  - OBJECTIVE: To observe the influence of tumor necrosis factor-alpha (TNFalpha) on
      skeletal muscle protein catabolism in rats with chronic obstructive pulmonary
      disease (COPD) and the effects of indomethacin (IND) on it. METHODS: Duplicated
      COPD model rats were divided into two groups: the malnutrition group and the
      normal nutrition group. The malnutrition group were further divided by randomized
      block design into four groups. Isotonic physiologic saline was administered to
      group A, the control and the normal nutrition group, and different doses of oral
      IND were administered to groups B, C, and D daily (group B: 0.5 mg*kg(-1)*d(-1);
      group C: 1 mg*kg(-1)*d(-1); group D: 2 mg*kg(-1)*d(-1)). The body weight,
      concentrations of TNFalpha, contents of 3-methyl-histidine (3-MH) and tyrosine
      (Tyr)in the diaphragm and extensor digitorum longus muscle homogenates were
      measured before and after the intervention. RESULTS: Before the intervention, the
      concentrations of TNFalpha in the serum of malnutrition groups were all
      significantly higher than those of normal nutrition group and the control
      group.After the intervention: (1) The concentrations of TNFalpha in the serum of
      the rats of group B, C and D were significantly lower than the group A,
      especially in group C. The levels of TNFalpha in serum and body weight of model
      group rats were negatively correlated (r = -0.846, P < 0.01), as well as the
      diaphragm and extensor digitorum longus muscle weights (r = -0.778, P < 0.01; r =
      -0.772, P < 0.01). (2) The levels of 3-methyl-histidine in the diaphragm and
      extensor digitorum longus muscles of the intervention group C was lower than the
      COPD normal nutrition group, as well as the intervention groups B and D. The
      contents of tyrosine in the diaphragm and extensor digitorum longus muscles of
      the intervention group C was lower than that of the COPD normal nutrition group,
      as well as the groups B and D. The body weight growth value of the intervention
      group B were slightly higher than the group A, without significant difference (P
      > 0.05), while the group C was significantly higher than the group A (P < 0.01).
      CONCLUSIONS: TNFalpha is involved in the occurrence of COPD malnutrition and
      skeletal muscle amyotrophy. IND can reduce the TNFalpha levels in the serum and
      the catabolic rates of the skeletal muscle proteins in malnutrition rats with
      COPD, so as to improve partly the skeletal muscle atrophy.

PMID- 21092452
TI  - [The expression of mucosal IL-1beta, TNFalpha and serotonin transporter in
      chronic visceral hypersensitivity rats].
AB  - OBJECTIVE: To assess the expression of TNFalpha, IL-1beta and the serotonin
      transporter (SERT) in adult rats of chronic visceral hypersensitivity induced by
      colon irritation during postnatal development, and to provide evidence to clarify
      the complex relationship between inflammatory cytokines and SERT among visceral
      hypersensitivity. METHODS: Sixteen neonatal male Sprague-Dawley rats were
      randomly separated into two groups undergoing different treatments. The irritated
      group (n = 8) was received intracolonic injections of acetic acid (0.5%) between
      postnatal days 8 and 21 and another group (n = 8) was received colonic infusion
      with 0.9% saline served as control. When they became adults (ages 7 weeks), the
      threshold intensity for a visually identifiable contraction of the abdominal wall
      and body arching were recorded during rectal distention (RD) to evaluate visceral
      hypersensitivity. Histological evaluation and MPO activity assay were performed
      to quantify the inflammation. The expression of cytokine of colon was assessed
      through immunohistochemistry. The expression of SERT was examined by Western
      blot. RESULTS: Histological examination of the tissues showed no significant
      structural damage or loss of crypts. The MPO levels in both groups were similar
      [(0.497 +/- 0.570) unit/g vs (0.623 +/- 0.739) unit/g, P = 0.724]. The threshold
      to elicit a distinctive abdominal muscle contraction in response to RD decreased
      from (0.40 +/- 0.14) ml in the control group to (0.19 +/- 0.06) ml in the
      irritated group. And the threshold for bodying arching decreased from (0.91 +/-
      0.26) ml in the control group to (0.47 +/- 0.13) ml in the irritated group (P <
      0.01). Cytokine immunoreactivity was increased in the irritated group when
      compared to the control group (TNFalpha: 0.194 +/- 0.001 vs 0.182 +/- 0.001, P <
      0.01; IL-1beta: 0.196 +/- 0.002 vs 0.185 +/- 0.001, P < 0.01), while SERT
      expression were reduced in the irritated group (0.298 +/- 0.038 vs 0.634 +/-
      0.200, P < 0.05). CONCLUSION: There is an increase in the proinflammatory
      cytokines and a decrease in the SERT expression associated with the presence of
      chronic visceral hypersensitivity, both of them may play an important role in the
      pathogenesis of visceral hypersensitivity.

PMID- 21092453
TI  - [The effect of mannose-6-phosphate on adipocyte differentiation and its
      underlying molecular mechanism].
AB  - OBJECTIVE: Cathepsin K (CTSK) played an important role in adipocyte
      differentiation. The activation of CTSK needs to convey by mannose-6-phosphate
      receptors (M6PR) in osteoclasts. The aim of the present study was to identify the
      effects of mannose-6-phosphate (M6P) in adipocyte differentiation and its
      underlying molecular mechanism. METHODS: Oil red O staining, accumulation of
      cytoplasmic triglycerides and glycerine release were used to assess its effects
      on adipocyte differentiation in the 3T3-L1 cell line. The enzyme activity of CTSK
      was observed by laser confocal microscopy. The proliferation of 3T3-L1
      preadipocytes was detected by MTT methods. mRNA expression of M6PR was determined
      by RT-PCR. RESULTS: M6P could prevent adipocyte differentiation in a dose
      dependent manner as evidenced by absence of triglyceride accumulation and
      glycerol content. Statistical significance was showed when the concentrations of
      M6P were 5.0 mmol/L and 8.0 mmol/L respectively (P < 0.05). The mRNA expression
      of M6PR was detected during the whole process of adipocyte differentiation. With
      the increase of M6P concentration, enzyme activity of CTSK was inhibited in a
      concentration-dependent manner. MTT method showed that the absorbance at 570 nm
      of 3T3-L1 preadipocytes was 0.057 +/- 0.091, increased about 62.9% at 10.0 mmol/L
      compared with the control group (P < 0.05). CONCLUSION: M6P inhibits the terminal
      differentiation of adipocyte, which may be associated with its effect of blocking
      CTSK activity by competitive binding with M6PR.

PMID- 21092454
TI  - [A comprehensive understanding of T and B lymphocytes in the rejection responses
      of organ transplantation].

PMID- 21092456
TI  - [Evaluation of immune status of kidney transplant recipients by combined HLA-G5
      and sCD30].
AB  - OBJECTIVE: to study the relationship between the expression of serum human
      leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal
      graft in kidney transplant recipients and investigate the immune status of
      recipients with combined HLA-G5 and sCD30. METHODS: from January 2002 to November
      2008, a total of 66 kidney transplant recipients in our centre were selected as
      subjects and divided into three groups: stable function of renal graft (n = 38),
      acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum
      HLA-G5 and sCD30 were detected. There were two different immune conditions with
      acute/chronic allograft rejection and normal renal graft in kidney transplant
      recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity,
      specificity and critical value of the method were analyzed by the curve of
      receiver operating characteristic. RESULTS: the levels of HLA-G5 and sCD30 were
      significantly correlated with serum creatinine (r = -0.493, 0.691, both P <
      0.01). Within the first year post-transplantation, the sensitivity was 78.6% and
      the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical
      value 12.2 microg/L. After one year post-transplantation: the sensitivity was
      92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30
      critical value 10.3 microg/L. CONCLUSION: the immune state of recipients are
      evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.

PMID- 21092455
TI  - [Applications of monitoring human leukocyte antigen G and its inhibitory
      receptors in post-renal transplantation].
AB  - OBJECTIVE: to study the feasibility of human leucocyte antigen-G (HLA-G) as a
      post-transplantation prognostic biomarker and discuss the correlation of its
      receptor expression and the mechanisms. METHODS: a total of 215 recipients in our
      centre from February 2006 to June 2008 were divided into stable kidney function
      group (n = 173) and acute rejection group (n = 42). The soluble human leucocyte
      antigen-G5 (sHLA-G5) level in peripheral plasma was detected by ELISA. And the
      HLA-G receptor ILT-2, KIR2DL4 on T, B, NK lymphocytes were analyzed by flow
      cytometry (FCM). The sHLA-G5 cutoff level by ROC curve was employed to predict
      the events of acute post-transplantation rejection. And regression analysis was
      used to determine the association of sHLA-G5 with acute rejection. RESULTS: an
      optimal cutoff value of 139.0 microg/L could be defined for sHLA-G5 (sensitivity:
      63.6%, specificity: 82.1%, AUC: 0.780). Binary regression analysis showed that
      sHLA-G5 played an independent role on acute rejection (P = 0.019, OR = 0.039,
      95%CI: 2.091 - 5.661). The rate of HLA-G receptor ILT-2 on CD4(+)T cell, CD8(+)T
      cell and B cell in acute rejection group was statistically lower than that in
      stable kidney function group (21% +/- 7% vs 52% +/- 17%, 23% +/- 6% vs 39% +/-
      16%, 21% +/- 7% vs 39% +/- 16%, all P < 0.05). The expression of KIR2DL4 on NK
      cells in acute rejection group was statistically lower than that in stable kidney
      function group (31% +/- 10%vs 57% +/- 21%, P < 0.05). CONCLUSION: sHLA-G5 level
      may be predicted for acute rejection with a high sensitivity and specificity. The
      up-regulated expression of ILT-2 and KIR2DLT may contribute to immunology
      tolerance in peripheral circulation.

PMID- 21092457
TI  - [Immunoadsorption in highly sensitized renal transplant recipients].
AB  - OBJECTIVE: to investigate the efficacy and safety of protein A immunoadsorption
      (IA) therapy in the prevention of highly sensitized renal transplant recipients
      with acute rejection. METHODS: a retrospective analysis of preoperative clinical
      data was carried out in 12 renal transplant patients in our hospital from March
      2008 to October 2009 with a high level of panel reactive antibody (PRA). Serum
      PRA and IgG, IgM, IgA were detected at pre and post-treatment. The acute
      rejection responses and adverse effects were observed. RESULTS: at post
      treatment, PRA of both Class I and II antibody [14% (4%, 27%) vs 86% (73%, 98%),
      6% (0, 23%) vs 68% (34%, 88%), P < 0.01] and serum total IgG levels significantly
      decreased [(550 +/- 341) g/L vs (1301 +/- 393) g/L, P < 0.01]. IgA and IgM were
      also lower than those at pre-treatment [(144 +/- 78) g/L vs (185 +/- 93) g/L,
      (103 +/- 48) g/L vs (131 +/- 66) g/L, P < 0.01]. Five cases had acute rejection
      reversible by anti-thymocyte globulin (ATG) or combined IA (n = 2). Within 6
      months, 1 cases developed Aspergillus pneumonia, 2 cases of Pneumocystis carinii
      pneumonia were cured. CONCLUSION: IA therapy can reduce antibody levels in highly
      sensitized renal transplant recipients. When supplemented with induction therapy,
      it can effectively prevent and reduce rejection after renal transplantation.

PMID- 21092458
TI  - [Value of zinc transporter 8 autoantibody in the diagnostic classification of
      acute-onset diabetics].
AB  - OBJECTIVE: to explore the application significance of zinc transporter 8
      autoantibody (ZnT8A) in the diagnostic classification of acute-onset diabetics.
      METHODS: according to the status of glutamic acid decarboxylase antibody (GADA)
      and tyrosine phosphatase antibody (IA2-A), 453 acute-onset diabetics were divided
      into A+ subgroup (any antibody positive) and A- subgroup (both antibodies
      negative). A total of 555 type 2 diabetics and 405 healthy controls were
      recruited. The distribution and correlated factors of ZnT8A were analyzed in the
      acute-onset diabetic group and two subgroups (A+ and A-). The clinical
      characteristics were compared between the patients with ZnT8A positive alone and
      patients without any antibody. All these islet antibodies were measured by
      radioligand assay. RESULTS: the prevalence of ZnT8A in acute-onset diabetics was
      24.3% and it was significantly higher than that in type 2 diabetics (1.8%) and
      healthy controls (1.0%) (both P < 0.01). The frequency of ZnT8A in A+ subgroup
      was much higher than A- subgroup (29.7% vs 15.8%, P < 0.01). The positive rates
      of ZnT8A were much higher in all the subgroups with age at onset of < 30 yr than
      those with >= 30 yr (0 - 9, 34.9%; 10 - 19, 26.7%; 20 - 29, 26.3% vs >= 30 yr,
      18.3%; all P < 0.05); furthermore, the rates were also higher in BMI < 21.0
      kg/m(2) and 21.0 - 25.0 kg/m(2) subgroups than in BMI > 25.0 kg/m(2) subgroup
      (25.5% and 25.9% vs 8.7%, both P < 0.05). The ZnT8A level was only positively
      correlated with IA2-A titer (r = 0.165, P = 0.01), but not related to such
      factors as GADA titer, age at onset, duration, body mass index, HbA1c and CP
      levels (all P > 0.05). As compared with Ab- patients, the patients with ZnT8A
      positive alone had much higher insulin injection dosage [(35.5 +/- 9.3) U/d vs
      (29.8 +/- 14.7) U/d, P < 0.05], and much lower systolic blood pressures [(107 +/-
      15) mm Hg vs (113 +/- 16) mm Hg, P < 0.05] and diastolic blood pressures [(69 +/-
      12) mm Hg vs (73 +/- 12) mm Hg, P < 0.05]. CONCLUSION: ZnT8A testing may be
      applied in the diagnostic classification of acute-onset diabetics, especially in
      those without an evidence of GADA and IA2-A since it helps to identify a clinical
      phenotype which is more similar to the classic type 1 diabetes.

PMID- 21092459
TI  - [Role of measuring the expression levels of a proliferation-inducing ligand and
      its receptors by real-time fluorescence quantitative method in children with
      lymphoma].
AB  - OBJECTIVE: to investigate the role of a real-time fluorescence quantitative
      polymerase chain reaction (PCR) in measuring the expression levels of a
      proliferation-inducing ligand and its receptors expression levels in peripheral
      blood of children with lymphoma. METHODS: real-time fluorescence quantitative PCR
      was used to detect the expression levels of a proliferation-inducing ligand and
      its receptors in patients with Hodgkin disease (n = 10) or non-Hodgkin lymphoma
      (n = 37) and healthy control (n = 40). The correlation between the mRNA levels of
      a proliferation-inducing ligand and its receptors and differential stage of
      malignant lymphoma was analyzed. RESULTS: the results of 47 samples showed that
      the levels of proliferation-inducing ligand, B cell maturation antigen,
      transmembrane activator and CAML interactor in the peripheral blood of lymphoma
      in children were significantly higher than those in normal children (1.13 +/-
      0.09 vs 0.41 +/- 0.09, 1.22 +/- 0.11 vs 0.43 +/- 0.10, 0.89 +/- 0.12 vs 0.35 +/-
      0.08, all P < 0.05). The level of a proliferation-inducing ligand and its
      receptors had no significant difference between Hodgkin disease and non-Hodgkin
      lymphoma (P > 0.05). The level of a proliferation-inducing ligand in I-II stage
      (0.88 +/- 0.06, 0.90 +/- 0.08) of malignant lymphoma in children was
      significantly lower than that in III-IV stage (1.21 +/- 0.09, 1.23 +/- 0.09, P <
      0.05) while the level of its receptors between various stages showed no
      difference (P > 0.05). CONCLUSION: the real-time fluorescence quantitative PCR
      has a high sensitivity and reproducibility. A proliferation-inducing ligand may
      play a great role in the development and progression of malignant lymphoma in
      children through its receptors of B cell maturation antigen, transmembrane
      activator and CAML interactor. A proliferation-inducing ligand and its receptors
      can be established as target molecules for early diagnosis and anti-cancer
      therapy.

PMID- 21092460
TI  - [Expression of SM22alpha and its relationship with lymph node metastasis in
      breast cancer].
AB  - OBJECTIVE: to analyze the relationship between the expression of SM22alpha and
      the lymph node (LN) metastasis of breast cancer and to investigate its molecular
      mechanisms. METHODS: reverse transcription-polymerase chain reaction (RT-PCR) was
      performed to detect the expression of SM22alpha in breast cancer tissue and
      adjacent normal breast tissue. RT-PCR and Western blot were employed to
      investigate the SM22alpha mRNA and protein level in tissues of breast
      fibroadenoma, breast cancer without LN metastasis and breast cancer with LN
      metastasis. RT-PCR and zymography were used to detect the MMP2 and MMP9
      expression and activity and TIMP1 expression level in breast fibroadenoma, breast
      cancer samples without LN metastasis and those with LN metastasis respectively.
      RESULTS: the expression level of SM22alpha mRNA in breast cancer was
      significantly lower than that in breast fibroadenoma or adjacent normal breast
      tissue (5.1% +/- 2.4% vs 15.1% +/- 5.3% vs 30.1% +/- 5.1%, P < 0.01). The protein
      and mRNA expression level of SM22alpha in breast cancer samples with LN
      metastasis were significant lower than those of breast cancer without LN
      metastasis (6.2% +/- 3.1% vs 10.1% +/- 4.1%, P < 0.01). Both the expression and
      activity of MMP2 and MMP9 in breast cancer samples with LN metastasis were
      significant higher than those without LN metastasis (P < 0.01). A strong negative
      correlation was found between SM22alpha protein level and MMP2 activity (r = 
      0.848; n = 27; P < 0.01) or MMP9 activity (r = -0.916; n = 27; P < 0.01) in
      breast cancer tissue. CONCLUSION: a down-regulation of SM22alpha in breast cancer
      is correlated with LN metastasis. SM22alpha may inhibit the LN metastasis through
      a negative regulation of MMP2 and MMP9 in breast cancer.

PMID- 21092461
TI  - [One-stage anteroposterior hemi-vertebra resection and segmental internal
      fixation for young children with congenital scoliosis].
AB  - OBJECTIVE: to discuss the feasibility and efficacy of one-stage anteroposterior
      hemi-vertebra resection and segmental internal fixation for young children with
      congenital scoliosis. METHODS: thirty-five patients undergoing one-stage
      anteroposterior hemi-vertebra resection and segmental internal fixation were
      retrospectively studied. The mean followed-up period was 5.3 years (range: 1.2 -
      8.7). The Cobb's angle of scoliosis at pre and post-operation was compared.
      RESULTS: all children's parents were satisfied with the outcome. The Cobb's angle
      of scoliosis was corrected from (42.5 +/- 6.7) degrees  to (16.2 +/- 3.2) degrees
      at post-operation. The coronal correction rate was 64.7%. The angle of kyphosis
      improved from preoperative (33.5 +/- 5.2) degrees  to postoperative (13.3 +/-
      5.6) degrees  in 14 cases. Operative duration was 210 - 280 minutes with an
      average of 240 minutes. The intra-operative blood loss was 80 - 200 ml with an
      average of 120 ml. There was no significant correction loss at follow-up. No
      neurological complication, infection or pedicular fracture was reported.
      CONCLUSION: the procedure of one-stage anteroposterior hemi-vertebra resection
      and segmental internal fixation is a safe and effective treatment for scoliosis
      by congenital hemi-vertebra in young children. A satisfactory correction may be
      achieved with a short fusion segment.

PMID- 21092462
TI  - [Change of airway inflammation induced by Th1/Tc1 and the expression of T
      regulatory cells in smoking cessation rats].
AB  - OBJECTIVE: to study the change of airway inflammation induced by Th1/Tc1 and the
      expression of CD4(+)CD25(+) regulatory T cells (Treg) in smoking cessation rats.
      METHODS: fifty healthy male Wistar rats were randomly divided into five groups:
      12-week normal control (group A, n = 10), 24-week normal control (group B, n =
      10), 12-week smoke exposure (group C, n = 10), 24-week smoke exposure (group D, n
      = 10) and smoking cessation (group E, n = 10). Groups C, D and E were exposed to
      cigarettes for 12 weeks. At Week 12, groups A and C were sacrificed. Group D
      continued smoke exposure and group E had smoking cessation for 12 weeks. At Week
      24, groups B, D and E were sacrificed. Pathomorphological changes of small airway
      were analyzed. The cells in BALF (bronchoalveolar lavage fluid) were collected
      and analyzed by absolute and differential cell counts. Enzyme linked
      immunosorbent assay (ELISA) was used to detect the levels of IFN-gamma, IL-4, IL
      8 and TNF-alpha. And flow cytometry was employed to determine the Foxp3 + Treg
      cell populations and reverse transcription-polymerase chain reaction (RT-PCR) to
      assay the mRNA expression for Foxp3. RESULTS: (1) compared with groups A and B,
      the airway inflammation score of groups C, D and E increased significantly (all P
      < 0.01). Compared with group C, the airway inflammation score of groups D and E
      both increased (all P < 0.01), especially group D; (2) compared with groups A and
      B, the levels of IFN-gamma, TNF-alpha and IL-8 in groups C, D and E increased
      (all P < 0.01) while those of IL-4 decreased. The levels of IFN-gamma, TNF-alpha
      and IL-8 showed no difference between groups C and E. The levels of IFN-gamma,
      TNF-alpha and IL-8 were higher in group D than those in groups C and E; (3) the
      ratio of Foxp3 + Treg cells in BALF was higher in group C (7.4% +/- 0.8%), group
      D (7.8% +/- 1.7%) and group E (7.0% +/- 1.4%) than group A (4.8% +/- 1.2%) and
      group B (4.7% +/- 1.2%) (all P < 0.01). There were no differences in the ratio of
      Foxp3 + Treg cells among groups C, D and E (all P < 0.05); (4) there was an
      elevated expression of Foxp3 mRNA in group C (0.22 +/- 0.02), group D (0.23 +/-
      0.03), group E (0.20 +/- 0.04) versus group A (0.13 +/- 0.01) and group B (0.11
      +/- 0.02) (all P < 0.01). But there was no difference in the expression of Foxp3
      mRNA among groups C, D and E (all P > 0.05). CONCLUSIONS: airway inflammation
      induced by Th1/Tc1 and an elevated expression of Treg cells in BALF are found in
      smoke exposure rats. Upon smoking cessation, the above-mentioned airway
      inflammation still persists and the expression of Treg cells in BALF shows no
      decrease. It suggests that an immune imbalance may be involved in the progression
      of Th1/Tc1-induced airway inflammation upon smoking cessation.

PMID- 21092463
TI  - [Effects of Helicobacter pylori, omeprazole and gastrin on the proliferation and
      apoptosis of gastric epithelial cell].
AB  - OBJECTIVE: to explore whether there is an interaction between Helicobacter pylori
      (H. pylori), omeprazole and gastrin on the proliferation and apoptosis of gastric
      epithelial cells. METHODS: With omeprazole, H. pylori and gastrin as treatment
      factors, the in vitro changes of gastric epithelial cells AGS and GES-1 were
      detected by MTS, Hoechst33342 and flow cytometry. RESULTS: (1) for a single
      factor, the gastric mucosal cells (AGS and GES-1) treated by H. pylori or
      omeprazole show significantly higher apoptosis than that of control group [H.
      pylori and 104 nmol/L omeprazole group: (17.20 +/- 0.90)%, (12.81 +/- 0.78)% vs
      (7.96 +/- 1.25)%; (4.60 +/- 0.34)%, (6.60 +/- 0.76)% vs (3.52 +/- 0.16)%; all P <
      0.05]. The gastric mucosal cells treated by H. pylori or omeprazole show
      significantly lower proliferation than that of control group (H. pylori and 104
      nmol/L omeprazole group: 13.35 +/- 0.55 vs 37.78 +/- 1.98, 47.62 +/- 2.40 vs
      62.44 +/- 4.46; 27.15 +/- 1.64 vs 32.76 +/- 1.57, 29.42 +/- 1.44 vs 48.86 +/-
      4.95; all P < 0.05). The differences were statistically significant and the
      effects were correlated with the concentration of omeprazole. Gastrin had no
      direct effect on cellular proliferation and apoptosis (all P > 0.05). (2) For a
      combinations of factors, the GES-1 cells treated with H. pylori and 500 ng/L
      gastrin had a significantly higher ratio [(7.25 +/- 0.54)% vs (4.60 +/- 0.34)%, P
      < 0.05], while the other groups just showed a rising trend in the proportion of
      apoptosis cells, but there was no statistical significance. Flow cytometry
      analysis showed that combinations of H. pylori, omeprazole and gastrin caused
      lower proliferation than that of H. pylori group, and all changes were
      statistically significant (AGS: 12.68 +/- 0.09, 12.28 +/- 0.31 vs 13.35 +/- 0.55;
      GES-1: 22.06 +/- 1.61, 18.59 +/- 0.09 vs 27.15 +/- 1.64; all P < 0.05). And
      combinations of 104 nmol/L omeprazole and 500 ng/L gastrin caused lower
      proliferation than that of 104 nmol/L omeprazole group (33.23 +/- 5.98 vs 47.62
      +/- 2.40 and 25.97 +/- 0.74 vs 29.42 +/- 1.44, both P < 0.05). (3) When comparing
      the apoptosis and proliferation changes of two cell lines, gastric cancer cells
      AGS had a more marked changes than immortalized cells GES-1. CONCLUSION: gastrin
      significantly enhances the effects of omeprazole and H. pylori on gastric
      epithelial cells. It is speculated that the factors of omeprazole, H. pylori and
      gastrin may have a synergistic effect of decreased proliferation and increased
      apoptosis of gastric mucosal cells. Thus a long-term proton pump inhibitor
      treatment of H. pylori patients may carry a higher risk of atrophic gastritis.
      But it needs to be confirmed by further experiments.

PMID- 21092464
TI  - [Expression of Cav-1, AQP1 and AQP5 in lung of acute pancreatitis-associated lung
      injury rats and the therapeutic role of Qingyitang].
AB  - OBJECTIVE: to investigate the expression and location of caveolin-1 (Cav-1),
      aquaporin 1 (AQP1) and AQP5 in the lung of acute pancreatitis-associated lung
      injury rats and to determine the role of these molecules in the pathologic
      progress and the potential therapeutic mechanisms of Qingyitang. METHODS: forty
      Wistar rats were randomly divided into sham operation (SHAM) group, acute lung
      injury (ALI) group, dexamethasone (DEX) group and Qingyitang (QYT) group. ALI was
      induced by reverse injection of deoxycholate into biliopancreatic duct of rats.
      Blood and lung tissues were collected after 24 h. Serum amylase, lung wet/dry
      (W/D) ratio and pathological section were detected to evaluate the degree of lung
      injury. reverse transcription-polymerase chain reaction was taken to detect the
      mRNA levels of Cav-1, AQP1 and AQP5. Lipid rafts were prepared for detection of
      the distribution and expression level of Cav-1, AQP1 and AQP5 proteins by Western
      blot. RESULTS: the concentration of serum amylase, the value of W/D and the
      degree of pathological lung injury obviously increased in ALI rats. Cav-1, AQP1
      and AQP5 were present in the lung while the mRNA level decreased in ALI rats. Cav
      1 appeared mainly in lipid rafts and less in non-lipid rafts. AQP1 was localized
      to lipid rafts while AQP5 to non-lipid rafts. The localization of these three
      molecules in the lung of ALI rats did not change compared with SHAM rats while
      their protein levels decreased. Compared with ALI rats, the concentration of
      serum amylase, the value of W/D and the degree of pathological lung injury
      obviously decreased in DEX and QYT rats. The mRNA and the protein expression of
      Cav-1, AQP1 and AQP5 increased in various degrees by DEX or QYT treatment.
      CONCLUSION: Cav-1 and AQP1 are enriched in lipid rafts while AQP5 in non-lipid
      rafts. The down-regulated expression of these three molecules may play important
      role in acute pancreatitis-associated lung injury. DEX and QYT may relieve lung
      injury effectively by up-regulating the expressions of Cav-1, AQP1 and AQP5.

PMID- 21092465
TI  - [Glycosylation modifications improve secretion and activity of intein spliced
      coagulation factor VIII].
AB  - OBJECTIVE: to investigate the effect of glycosylation modification on secretion
      of intein spliced B-domain-deleted FVIII (BDD-FVIII). METHODS: a total of 226
      amino acid residues of FVIII B domain with six potential asparagines-linked
      glycosylation sites (N6) were incorporated into heavy chain of BDD-FVIII. By dual
      vector co-transfer of heavy and light chain genes with fused intein (N6HCIntN and
      IntCLC) into cultured 293 cells, the amounts of spliced BDD-FVIII protein and
      coagulation activity in culture supernatant were observed by ELISA and Coatest
      method respectively. RESULTS: the amounts of spliced BDD-FVIII protein and
      activity were up to (123 +/- 18) ng/ml and (0.94 +/- 0.11) U/ml in supernatant
      from cells co-transfected with N6HCIntN and IntCLC genes. And they were higher
      than those of cells co-transfected with intein-fused heavy (HCIntN) and light
      chain (IntCLC) genes [(86 +/- 12) ng/ml and (0.65 +/- 0.07) U/ml, both P < 0.05].
      Spliced BDD-FVIII protein and activity could also be detected in the supernatant
      from mixed cells individually transfected with N6HCIntN and IntCLC genes [(18 +/-
      6) ng/ml and (0.15 +/- 0.05) U/ml]. CONCLUSION: it demonstrated that the
      glycosylation modified heavy chain can improve the secretion of intein spliced
      BDD-FVIII and the protein splicing can occur independent of cellular mechanism.

PMID- 21092466
TI  - [Regulation of vascular tension in diabetic coronary artery by large conductance
      Ca(2+)-activated K(+) channel in rats].
AB  - OBJECTIVE: to investigate the regulation in vascular tension of diabetic coronary
      artery by large conductance Ca(2+)-activated K(+) channel (BK channel) and to
      elucidate the mechanisms of coronary dysfunctions due to diabetes. METHODS:
      regulation of vascular tension in normal coronary artery was evaluated by
      videomicroscopy system. Streptozotocin-induced rat diabetic animal model was
      established successfully by intraperitoneal injection. Coronary smooth muscle
      cells were isolated by enzyme digestion. The BK currents in control and diabetic
      groups were recorded by patch clamp technique in whole cell configuration.
      Changes of vascular tension in normal and diabetic coronary arteries were assayed
      by multi-wire myograph system. RESULTS: more than 50% was contracted in inner
      diameters of coronary arteries when 100 nmol/L IBTX, a specific BK channel
      blocker, was applied. In comparison with normal group, the BK current densities
      in diabetic group significantly decreased when test potentials were more than 60
      mV (P < 0.05). The BK current densities at 150 mV in normal group and diabetic
      group were (275 +/- 40) pA/pF and (70 +/- 10) pA/pF respectively. When 100 mmol/L
      KCl was washed out, vascular tensions of normal and diabetic coronary artery were
      (398 +/- 38) mg and (390 +/- 35) mg respectively (P > 0.05); however, when 100
      nmol/L IBTX was added, the vascular tensions of normal and diabetic coronary
      artery were (395 +/- 40) mg and (50 +/- 7) mg (P < 0.05). CONCLUSION: BK channels
      play an important role in the regulation of coronary vascular tension, whereas BK
      channels in diabetic coronary artery are dysfunction, BK currents decrease and
      vascular tensions increase.

PMID- 21092467
TI  - [The investigation of coexistence of cervical and lumbar multiple segment spine
      disease].

PMID- 21092468
TI  - [Anterior cervical discectomy and fusion in the treatment of Hangman's fracture].
AB  - OBJECTIVE: To evaluate the efficacies and features of treating Hangman's fracture
      by anterior cervical discectomy and fusion (ACDF). METHODS: Since June 2005 to
      December 2008, 36 cases with Hangman's fracture were analyzed with their clinical
      data including history, symptoms, signs, radiological findings and treatments.
      According to the classification system designed by Levine and Edwards depending
      on the radiological manifestations of Hangman's fractures, they were subdivided
      into type I (n = 9) (conservative therapy), type II (n = 17) and type IIA (n =
      10). Conservative therapy was offered to type I in 9 cases, while ACDF with
      cervical gear protection for 4 weeks after surgery was performed to type II in 17
      cases and type IIA in 10 cases. A combination of operation time, days of
      hospitalization, complications, neurological improvement and fusion rate was
      assessed. RESULTS: An average follow-up of 15 months (range: 10 - 36) was
      achieved. No vertebral redisplacement and angulation deformity occurred. Axial
      pain was relieved in each case. The preoperative neurological deficits in all
      patients got improvements. No spinal cord injury, vertebral artery injury or
      cerebrospinal fluid leakage occurred. No complication related to internal fixator
      was found. Average operative time and hospitalization were similar to those of
      ACDF for lower cervical spine (98 minutes vs. 9 days). Fusion was achieved within
      6 months in all cases. CONCLUSION: ACDF at C2-C3 may be an effective and safe way
      to treat Hangman's fracture.

PMID- 21092469
TI  - [The clinical effect and disquisition of anterior cervical approach surgery with
      posterior longitudinal ligament hook pliers and posterior longitudinal ligament
      nip pliers].
AB  - OBJECTIVE: To study the clinical effect of anterior cervical approach surgery to
      removal posterior longitudinal ligament (PLL) with posterior longitudinal
      ligament hook pliers and posterior longitudinal ligament nip pliers. METHODS: To
      retrospectively analyzed anterior cervical approach surgery treatment 73 patients
      who were cervical spondylosis myelopathy. All patients removal PLL with self-make
      instrument, According to JOA grade to evaluate effect of operations. RESULTS:
      Full patients removal PLL were in succeed, in shape of extradural has renew, the
      JOA grade were increase, (12.8 +/- 3.2) vs (8.3 +/- 1.9). CONCLUSIONS: Removal
      PLL were increase effect of downright decompress in anterior cervical approach
      surgery, Operations become safety agile and reduce the complications with self
      make instrument.

PMID- 21092470
TI  - [Adjacent segment mobility after anterior cervical discectomy and fusion].
AB  - OBJECTIVE: To investigate the mobility changes of adjacent segments after fusion
      retrospectively. METHODS: A total of 28 patients underwent standard anterior
      cervical arthrodesis. The kinematic changes occurred at segments adjacent to
      cervical arthrodesis through a coral bone graft and plating system. The mean
      follow-up period was 6.3 +/- 1.6 years (3.6 - 10.5). Lateral radiographic views
      of cervical spine in flexion and extension were obtained at pre-operation and
      follow-up. Rotational motion at adjacent levels was quantified. RESULTS: Sagittal
      range of motion (ROM) at adjacent cranial level was 11.2 degrees  +/- 5.0 degrees
      at pre-operation and 11.4 degrees  +/- 6.4 degrees  at follow-up. It was not
      statistically significant (P > 0.01). At adjacent caudal level, ROM was 9.8
      degrees  +/- 5.3 degrees , but 10.2 degrees  +/- 4.6 degrees  at follow-up. But
      it was not statistically significant (P > 0.01). During the follow-up, entire
      cervical motion (C2-C7) decreased significantly from 46.8 degrees  +/- 13.4
      degrees  to 36.8 degrees  +/- 9.6 degrees  in single-level fusion group, but from
      48.6 degrees  +/- 14.6 degrees  to 39.9 degrees  +/- 7.2 degrees  in double-level
      fusion group. CONCLUSION: The assumption of an iatrogenically elevated adjacent
      level mobility by cervical fusion is refuted by the present study.

PMID- 21092471
TI  - [Relationship between expression of MMP-9 and presyrinx state of experimental
      syringomyelia of rabbits].
AB  - OBJECTIVE: To investigate the relationship between the expression of MMP-9 and
      the formation of spinal cord edema in presyrinx state of experimental
      syringomyelia in rabbits and evaluate the inhibitory function of doxycycline in
      the formation of spinal cord edema in presyrinx state. METHODS: A total of 96
      Chinese white rabbits were divided randomly into four groups:kaolin group (n =
      24), doxycycline treatment group (n = 24), physiological saline group (n = 24)
      and control group (n = 24). Under ketamine anesthesia, 0.6 ml of 25% kaolin
      solution was injected into the cisterna magna in all rabbits of kaolin and
      doxycycline groups while 0.6 ml of 37 degrees C physiological saline into the
      cistern in those of saline group; doxycycline (25 mg * kg(-1) * d(-1)) was
      applied post-operatively for doxycycline group. At Days 1, 3, 7 and 14 after
      kaolin injection, 6 rabbits of all four groups were selected randomly for
      sacrificing. Water content of spinal cord could be obtained. The expression of
      MMP-9 activity was measured by Western blot and immunohistochemistry. RESULTS: At
      any time point, the water content of spinal cord and the expression of MMP-9 in
      kaolin group improved obviously more than those of saline and control groups (P <
      0.01). At Day 1, there was no marked difference in the water content of spinal
      cord and the expression of MMP-9 between doxycycline and kaolin groups (P >
      0.05). At other time points, the water content of spinal cord and the expression
      of MMP-9 in doxycycline group markedly decreased than those of kaolin group (P <
      0.01). CONCLUSION: In the model of experimental syringomyelia, MMP-9 plays an
      important role in causing edema in presyrinx state. Thus doxycycline may be used
      to prevent and treat syringomyelia.

PMID- 21092472
TI  - [Severe fungal corneal ulcer resulting in infectious endophthalmitis].
AB  - OBJECTIVE: To analyze causes of serious fungal corneal ulcer resulting in
      infectious endophthalmitis and explore clinical strategies of avoiding the
      failure of antifungal therapy. METHODS: Etiological factors, pre-hospital
      treatments, clinical features and laboratory findings of 47 inpatients with
      fungal corneal ulcer resulting in endophthalmitis from January 1999 to December
      2008 in Qingdao eye hospital were retrospectively reviewed. RESULTS: Rural
      residents (95.7%) dominated in 47 cases with a mean age of (49.8 +/- 10.1) years.
      Ocular trauma was the leading cause of fungal corneal ulcer (66.0%). Three
      patients were ever treated with hormone drugs after the fungal infection.
      Primary, secondary and tertiary hospital accounted for 68.1%, 17.0% and 14.9%
      among first medical consultation sites. Diagnostic accuracies of fungal corneal
      ulcer in three grade hospitals were 31.3%, 62.5% and 71.4% respectively. The
      average interval from the onset of disease to the admission into our hospital was
      (29 +/- 23) days. The dominating pathogen was genus Fusarium (91.5%) with F.
      solani (48.9%), F. oxysporum (31.9%) and F. moniliforme (8.5%). Antifungal drug
      sensitivity tests were performed in 21 patients. The first three sensitive drugs
      were natamycin (88.9%), voriconazole (78.6%) and amphotericin B (61.9%). The
      first three drug-resistant ones were miconazole (90.5%), fluconazole (66.7%) and
      itraconazole (61.9%). CONCLUSION: Main causes of fungal corneal ulcer resulting
      in infectious endophthalmitis included lower diagnostic accuracies of first
      medical consultation in primary hospitals, abuses of non-sensitive drug and
      delayed treatment of patients. Improving clinical capabilities of doctors in
      primary hospitals, emphasizing antifungal drug susceptibility tests, and
      consummating the social security system and the referral system could be
      effective measures to avoid therapeutic failures.

PMID- 21092473
TI  - [Comparison and clinical significance between geometrical characteristics of
      tibial plateau between Uighur nationality and Han people].
AB  - OBJECTIVE: To compare the difference and clinical significance of geometrical
      characteristics of tibial plateau between Uighur nationality and Han people by
      computed tomography scan and three-dimensional reconstruction. METHODS: A total
      of 49 inpatients and outpatients were randomly selected (normal knee without any
      tibial involvement) and volunteers of Han people and 45 ones of the Uighur
      nationality at our hospital and cooperative hospitals. Then the subjects were
      divided into groups according to gender. The following linear geometric
      parameters of tibial plateau were measured: width of tibial plateau (WTP), width
      of medial tibial plateau (WMTP), sagittal length of medial tibial plateau
      (SLMTP), width of lateral tibial plateau (WLTP) and sagittal length of lateral
      tibial plateau (SLLTP). RESULTS: (1) Males were greater than females in linear
      parameters in the same group (P < 0.01); (2) the groups of Uighur nationality
      were greater than groups of Han people in linear parameters in the same gender (P
      < 0.05); (3) the gaps between WMTP and WLTP, SLMTP and SLLTP of Uighur
      nationality were all more approximate than those of Han people (P < 0.05).
      CONCLUSION: The geometrical characteristics of tibial plateau have some visible
      discrepancy between Uighur nationality and Chinese Han people. The prosthetic
      design concept and technology of total knee replacement targeting the Uighur
      nationality should take into consideration the discrepancy.

PMID- 21092474
TI  - [Efficacy and safety of high-dose alpha-lipoic acid in the treatment of diabetic
      polyneuropathy].
AB  - OBJECTIVE: To evaluate the efficacy and safety of high-dose alpha-lipoic acid in
      the treatment of diabetic polyneuropathy with regards to sensory symptoms and
      nerve conduction velocity. METHODS: A total of 236 diabetics with symptomatic
      polyneuropathy were enrolled into this 5-center, randomized, double-blind and
      placebo-controlled study of alpha-lipoic acid 1800 mg daily (n = 117) or matching
      placebo (n = 119) for 12 weeks. The primary outcome was total symptom score
      (TSS). Secondary end points included nerve conduction velocity, individual
      symptom score, HbA1c and safety parameters. The above parameters were reviewed
      and recorded at zero point and after treatment for 2, 4, 8, 12 weeks separately.
      RESULTS: 73.27% patients with symptomatic polyneuropathy improved after treatment
      with alpha-lipoic acid for 12 weeks versus 18.27% with placebo. TSS declined by
      2.6 +/- 2.3 with alpha-lipoic acid. And it was more than 0.7 +/- 1.4 versus
      placebo (P < 0.05). TSS decreased quickly after treatment with alpha-lipoic acid
      for 2 weeks (P < 0.05). And it was better than placebo. Individual symptom scores
      of pain, extremity numbness, burning sensation or resting abnormal sensations
      were significantly diminished as compared to those before treatment and placebo
      group (all P < 0.05). Nerve conduction velocity had no change. HbA1c further
      decreased at the end of trial after alpha-lipoic acid treatment (P < 0.05). The
      incidence rates of adverse effects were 25.4% vs 11.8% in the treatment and
      control groups. The major manifestation was burning sensation from throat to
      stomach (12.7%). CONCLUSION: Oral treatment with high-dose alpha-lipoic acid for
      12 weeks may improve symptoms in patients with diabetic polyneuropathy. Dose of
      600 mg thrice daily for 2 weeks has marked effects with a reasonable safety.

PMID- 21092475
TI  - [Neuromyelitis optica IgG and related clinical features of patients with
      neuromyelitis optica].
AB  - OBJECTIVE: To investigate the differential diagnostic value of NMO-IgG for
      neuromyelitis optica (NMO) versus multiple sclerosis (MS) and to analyze its
      possible clinical features related to NMO-IgG. METHODS: Forty-one NMO patients
      and 44 MS patients in acute phase and 40 healthy controls were investigated.
      Serum NMO-IgG was tested by indirect immunofluorescence assay. The disability
      severity in NMO and MS patients was assessed by Expanded Disability Status Scale
      (EDSS). Clinical features and MRI imaging profiles were analyzed between NMO-IgG
      positive patients and negative ones. RESULTS: 70.7% (29/41) NMO patients were NMO
      IgG positive compared to 9.1% (4/44) MS patients and all healthy controls were
      NMO-IgG negative (P < 0.01). The sensitivity and specificity were 70.7% and 90.9%
      respectively when NMO-IgG was used to discriminate NMO from MS. NMO patients with
      positive NMO-IgG had significantly higher EDSS scores (P < 0.05). More NMO-IgG
      seropositive patients had longitudinally extensive cord lesions (>= 3 segments)
      than the NMO-IgG seronegative patients (93.1% vs 66.7%). But the difference was
      insignificant. CONCLUSION: NMO-IgG is a specific biomarker of NMO. NMO-IgG can
      facilitate an early differentiation of NMO from MS. NMO-IgG seropositivity is
      related to graver symptoms and it may predict an aggravation.

PMID- 21092476
TI  - [An open-label, multicentric clinical trial to evaluate the efficacy and impact
      on bone metabolism of recombinant human tumor necrosis factor-alpha receptor II
      IgG Fc fusion protein with methotrexate in active rheumatoid arthritis: 24-week
      clinical and radiographic results from ReABLE study].
AB  - OBJECTIVE: To evaluate the efficacy, radiographic changes and safety of the
      combination of recombinant human tumor necrosis factor-alpha receptor II IgG Fc
      fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid
      arthritis (RA). METHODS: 30 RA patients were treated with rhTNFR:Fc (25 mg
      subcutaneously twice weekly) and oral MTX (up to 15 mg weekly) in an open-label
      manner. Clinical response was assessed by American College of Rheumatology (ACR)
      criteria and Disease Activity Score in 28 joints (DAS28). Radiographs of hands
      and wrist were assessed by the modified Sharp score. RESULTS: At Week 24, ACR20,
      ACR50 and ACR70 responses were achieved by 90%, 76.67% and 46.67% respectively.
      At Week 24, the mean DAS28 was 3.65 +/- 1.26 versus 6.41 +/- 0.61 at baseline (P
      < 0.001). And 20% patients achieved remission and 16.67% patients had a low
      disease activity. At week 24, EULAR good and moderate responses were attained by
      36.67% and 60% respectively. Similarly, Health Assessment Questionnaire (HAQ)
      improved significantly, declining from 1.12 at baseline to 0.36 at week 24 (P <
      0.001). No radiographic progression (based on change of total Sharp score) was
      found in 27 cases. Adverse events were mild. CONCLUSION: rhTNFR:Fc in combination
      with MTX shows an excellent efficacy of reduced disease activity, improved
      function and slowed radiographic progression through 24 weeks. A combination
      therapy for 24 weeks can lead to disease remission and an inhibition of
      radiographic progression. Further study is warranted.

PMID- 21092477
TI  - [The efficacy analysis of endovascular intervention therapy for transatlantic
      inter society consensus type C and type D femoropopliteal arteriosclerosis
      lesion].
AB  - OBJECTIVE: To evaluate the efficacy of the endovascular intervention for
      transatlantic inter society consensus (TASC) type C and type D femoropopliteal
      artery disease. METHODS: We conducted a retrospective analysis on 95 cases (98
      lower limbs) with TASC type C and type D femoropopliteal artery arteriosclerosis
      lesion treated by percutaneous transluminal angioplasty and/or primary stent
      implantation from January 2007 to April 2009. We used ankle brachial index (ABI),
      Fontaine stages, limb salvage percentage and primary patency to evaluate the
      efficacy of the endovascular intervention therapy. RESULTS: The technical success
      rate of the 98 limbs was 94.9%, the perioperation mortality was 4.2% and the
      total amputation rate was 5.1%. 81 cases (84 limbs) were followed-up for a mean
      time of (13 +/- 7) months, whose average ABI in dorsalis pedis artery and
      posterior tibial artery were 0.58 +/- 0.22 and 0.60 +/- 0.21 and increased 0.14
      +/- 0.25 and 0.13 +/- 0.22 respectively than the ABI before intervention therapy.
      The statistical analysis showed a significant difference in ABI. The limbs of
      critical limb ischemia (CLI) were of 16.4% in the follow-up period and of 73.5%
      before the intervention therapy. The statistical results showed a significant
      difference in the percentage of CLI. CONCLUSION: Percutaneous endovascular
      intervention is an effective and minimally invasive method, and has a curative
      clinical efficacy to treat TASC type C and type D femoropopliteal artery disease.

PMID- 21092478
TI  - [Comparison of surgery for staging using laparoscopy and laparotomy in patients
      with endometrial cancer].
AB  - OBJECTIVE: To compare the surgical outcomes for staging by laparoscopy and
      laparotomy in patients with endometrial cancer, evaluate the feasibility of
      laparoscopic surgical treatment of endometrial cancer, compare the difference
      between clinical and surgical staging of endometrial cancer and elucidate the
      advantages and feasibility of its surgical staging. METHODS: Fifty-six patients
      diagnosed pre-operatively as stage I endometrial cancer were reviewed for surgery
      for staging. They were assigned into laparoscopic group (n = 34) and laparotomic
      (open) group (n = 22). The operative parameters including operating time, intra
      operative blood loss, the number of lymph nodes removed, gastrointestinal
      recovery time, urinary catheterization time, complications and post-operative
      hospital stay were compared. RESULTS: The pre-operative clinical characteristics
      before operation between two groups were similar. No significant differences were
      found in age and body mass index between two groups. As compared with the open
      group, the laparoscopic group had a longer operation time (213 min +/- 49 min vs
      162 min +/- 30 min, P < 0.05), less hemoglobin change (12 g/L +/- 8 g/L vs 19 g/L
      +/- 8 g/L, P < 0.05), shorter hospital stay (6.3 d +/- 1.7 d vs 9.5 d +/- 1.8 d,
      P < 0.01) and shorter gastrointestinal recovery time (1.8 d +/- 0.6 d vs 2.7 d +/
      1.2 d, P < 0.01). While there was no significant difference between two groups
      in the number of lymph nodes removed, urinary catheterization time, costs and
      complications. The total coincidence was 57.14% between clinical and surgical
      staging. CONCLUSION: Laparoscopic staging surgery is both feasible and safe in
      the treatment of endometrial cancer. And the surgical staging truly reflects the
      extent of cancer invasion and it is thus necessary for early-stage endometrial
      cancer.

PMID- 21092479
TI  - [To explore treatment of neurogenic tumors of the peripheral nerve].
AB  - OBJECTIVE: To discuss the clinical features and surgical tactics of neurogenic
      tumors external spinal canal. METHODS: The investigators retrospectively analyzed
      the clinical data of 56 cases with neurogenic tumors external spinal canal as
      confirmed by pathology at our department from January 2000 to June 2010. And the
      follow-up results were tracked. Among the patients, 51 cases underwent
      microsurgery and 5 cases routine retro-peritoneal operation. RESULTS: Fifty cases
      received total resection and 5 cases subtotal resection. Partial tumor removal
      was performed in 1 case with multiple Schwannoma only because nerve roots were
      densely distributed around the tumor. Postoperative complications included
      declining myodynamia (n = 3), extremity pain (n = 2), topical sensory disturbance
      (n = 7), hoarseness (n = 5), ipsilateral facioplegia & hypophysis (n = 1) and
      Horner's syndrome (n = 2). Thirty-six cases had a follow-up period of 0.5 year to
      10 years. No in situ recurrence was found in 34 cases. Two cases with in situ
      recurrence were re-operated. There was no operative death. CONCLUSION: The
      surgery of neurogenic tumors external spinal canal can improve the symptoms and
      quality of life for the patients. A better outcome is based on anatomic
      familiarity and skilled micromanipulation. The key aspects of tumor resection are
      a maximal protection of proximal important vessels and nerves and thorough tumor
      dissection.

PMID- 21092480
TI  - [Clinical features and genetic diagnosis of Kennedy disease].
AB  - OBJECTIVE: To outline the clinical features of Kennedy disease in Chinese
      patients. METHODS: The peripheral blood was collected from the male lower motor
      neuron disease patients of our inpatients and outpatients from July 2005 to
      September 2008. Then the genome DNA was extracted and the target gene amplified
      by polymerase chain reaction and sequenced. The clinical data of positive samples
      were analyzed and summarized. RESULTS: The number of expanded CAG repeats of 12
      patients ranged from 43 to 57. And the number of CAG repeats was inversely
      correlated with the age of onset (r = -0.756, P < 0.005). The first symptom of
      all of these patients was extremity weakness. The progression of disease was
      slow. One of the patients died from pneumonia. And the whole disease course
      lasted for 14 years. CONCLUSION: As an adult onset degenerative disease with a
      slower clinical progression, Kennedy disease has its own characteristics of
      inheritance pattern and natural course. It can be accurately diagnosed by
      androgen receptor gene analysis.

PMID- 21092481
TI  - [Clinical analysis of treating 174 cases with pulmonary tuberculosis by
      pneumonectomy].
AB  - OBJECTIVE: To evaluate the efficacy and indication of pneumonectomy in patients
      with pulmonary tuberculosis. METHODS: From January 1992 to the end of 2008, 174
      patients with pulmonary tuberculosis underwent pneumonectomy. According to the
      classification of pulmonary tuberculosis, there were tuberculous destroyed lungs
      (n = 106), chronic fibro-cavernous pulmonary tuberculosis (n = 27), cavernous
      pulmonary tuberculosis with aspergilloma (n = 5), tuberculous tracheobronchial
      stenosis (n = 16), pulmonary tuberculosis with encapsulated empyema (n = 5),
      tuberculous empyema with broncho pleural fistula (n = 4) and massive hemoptysis
      (n = 11). RESULTS: The surgical approaches were pneumonectomy (n = 146),
      pleuropneumonectomy (n = 21), chlorine pneumonectomy (n = 3), pneumonectomy with
      thoracoplasty (n = 1) and pneumonectomy with tracheoplasty (n = 3). The overall
      clinical cure rate was 93.0%, the rate of complications 11.5% and the operative
      mortality 2.3%. There were 3 dead cases resulting from operations in six months.
      CONCLUSION: Tuberculosis chemotherapy is an important modality for pulmonary
      tuberculosis, but surgical therapy remains essential for some patients.
      Pneumonectomy may increase the cure rates of severe pulmonary and multiple drug
      resistant tuberculosis.

PMID- 21092482
TI  - [Effects of blueberry on the proliferation and activation of hepatic stellate
      cell and its mechanism].
AB  - OBJECTIVE: To investigate the effects of blueberry on the proliferation and
      activation of hepatic stellate cell (HSC) and its mechanism. METHODS: Rat HSC
      were isolated by type IV collagenase digestion and Nycodenz density gradient
      centrifugation. The cultured HSC was incubated at different concentrations of 10%
      blueberry serum. The 10% DSHX serum was used as positive control and 10% normal
      rat serum group as control. MTT colorimetric assay was used to detect the HSC
      proliferation. ColI of culture supernatant was detected by ELISA. The expression
      of alpha-SMA in HSC was measured by immunocytochemistry staining while the
      expressions of Nrf2 and HO-1 were determined by Western blot. RESULTS: Compared
      with controls, the low and high-dose blueberry serum groups significantly
      inhibited the HSC proliferation (P < 0.05). It had the same inhibitory effects as
      the positive control serum group (P > 0.05). ColI of culture supernatant
      obviously decreased (P < 0.05). And the expression levels of alpha-SMA in low and
      high-dose blueberry serum groups decreased significantly (P < 0.05). And there
      were similar effects in low & high-dose blueberry serum and positive control
      serum groups. Western blot showed that the expressions of Nrf2 and HO-1 in
      blueberry and positive control serum groups were higher than that in control
      group. And the increment was more significant in the low and high-dose blueberry
      serum groups (P < 0.05). CONCLUSION: Blueberry can significantly inhibit the
      proliferation and activation of HSC and reduce the synthesis of extra-cellular
      matrix. It may have potential preventive and protective effects on hepatic
      fibrosis. The mechanism may be related to an elevated expression of HO-1 through
      the Nrf2 pathway.

PMID- 21092483
TI  - [Dynamic detection of duck hepatitis B virus cccDNA in serum of ducks with liver
      injury].
AB  - OBJECTIVE: To confirm whether DHBV cccDNA could be detected in serum of DHBV
      infected ducks after liver injury. METHODS: Twenty four ducks with persistent
      DHBV infection were divided into 4 groups with the following treatments: A, D
      galactosamine (D-GalN, 2.2 g/kg) and lipopolysaccharide (LPS, 100 ug/kg); B, 10
      mg/kg of carbon tetrachloride (CCl4) every 12 h twice following D-GalN and LPS;
      C, 15 mg/kg of CCl4 every 12 h twice following D-GalN and LPS; D, normal saline
      as normal control (NC). At 0 h, 24 h, 36 h and 48 h post-treatment, sera were
      collected from each duck for determination of serum DHBV load, DHBV cccDNA and
      alanine aminotransferase (ALT). And ducks were eventually sacrificed to obtain
      liver specimens for pathological assessment of liver lesions and determination of
      intrahepatic total DHBV DNA and DHBV cccDNA. RESULTS: (1) No obvious pathological
      change was observed in the liver of ducks from NC group while the indices of
      liver injury were significantly different between Groups A, B and C; (2) DHBV
      cccDNA was undetectable in the sera of ducks from NC and A group at all time
      points. In contrast, DHBV cccDNA, varying from 3.17 * 10(3) copies/ml to 1.72 *
      10(4) copies/ml, was detected in the sera of 2 ducks from Group B and 3 ducks
      from Group C at 36 h post-treatment. The occurrence of DHBV cccDNA in serum was
      significantly correlated with the degree of liver injury while no significant
      association with serum ALT level and DHBV load as well as with the level of
      intrahepatic total DHBV DNA and DHBV cccDNA was observed. CONCLUSION: DHBV cccDNA
      may be detected in the serum when the liver of duck is seriously damaged. The
      incidence of DHBV cccDNA occurrence in the serum is significantly associated with
      the severity of liver injury.

PMID- 21092484
TI  - [Development and clinical evaluation of an anesthesia information management
      system].
AB  - OBJECTIVE: To study the design, implementation and clinical evaluation of an
      anesthesia information management system. METHODS: To record, process and store
      peri-operative patient data automatically, all kinds of bedside monitoring
      equipments are connected into the system based on information integrating
      technology; after a statistical analysis of those patient data by data mining
      technology, patient status can be evaluated automatically based on risk
      prediction standard and decision support system, and then anesthetist could
      perform reasonable and safe clinical processes; with clinical processes
      electronically recorded, standard record tables could be generated, and clinical
      workflow is optimized, as well. RESULTS: With the system, kinds of patient data
      could be collected, stored, analyzed and archived, kinds of anesthesia documents
      could be generated, and patient status could be evaluated to support clinic
      decision. CONCLUSION: The anesthesia information management system is useful for
      improving anesthesia quality, decreasing risk of patient and clinician, and
      aiding to provide clinical proof.

PMID- 21092485
TI  - [Treatment and diagnosis of adult flatfoot].

PMID- 21092486
TI  - [Surgical treatment of flatfoot resulting from calcaneal fractures malunion].
AB  - OBJECTIVE: To explore the operative approach and efficacy of flatfoot after
      calcaneal fractures malunion. METHODS: A total of 116 flatfoot patients after old
      calcaneal fractures were treated from January 1998 to January 2008. There were 94
      males and 22 females with an average age of 33.5 years old (range: 16 - 46). They
      included unilateral flatfoot after old calcaneal fractures (n = 110) and
      bilateral flatfoot after old calcaneal fractures (n = 6). The surgical treatments
      included open reduction, calcaneal osteotomy without subtalar fusion or a
      reconstruction of calcaneal thalamus and subtalar arthrodesis. RESULTS: A total
      of 101 patients were followed up for an average of 14 months (range: 12 - 24). No
      wound healing problem or infection was observed. Solid union was obtained without
      redislocation in all patients. The mean time of bone union was 12 weeks (range:
      10 - 14). The mean time of complete weight loading was 13 weeks (range: 11 - 15
      weeks). The height of foot arch increased from 4.2 mm +/- 1.7 mm to 14.1 mm +/-
      4.1 mm (P < 0.05). Calcaneal inclination angle increased from 11.2 degrees  +/-
      2.5 degrees  to 19.1 degrees  +/- 4.4 degrees  (P < 0.05). Bohler angle increased
      from 5.4 degrees  +/- 3.5 degrees  to 25.8 degrees  +/- 5.2 degrees  (P < 0.05).
      Meary angle recovered from 22.2 degrees  +/- 4.4 degrees  to 5.1 degrees  +/- 3.2
      degrees  (P < 0.05). The mean AOFAS Ankle and Hindfoot score increased from 33.4
      (range: 27 - 43) to 85.8 (range: 78 - 98). CONCLUSION: As to flatfoot after old
      calcaneal fractures, surgical treatment has a favorable efficacy. A customized
      operative approach may achieve a satisfactory outcome.

PMID- 21092487
TI  - [Triple arthrodesis with osteotomy for the treatment of stage IIB and stage III
      adult-acquired flatfoot deformity].
AB  - OBJECTIVE: To analyze the clinical outcomes of triple arthrodesis with osteotomy
      in the treatment of Stage IIB and Stage III adult-acquired flatfoot. METHODS: The
      authors reviewed 10 cases of adult-acquired flatfoot, including 3 cases of stage
      IIB adult-acquired flatfoot and 7 cases of stage III adult-acquired flatfoot.
      They were treated by triple arthrodesis with osteotomy of subtalar joint (STJ),
      talonavicular joint (TNJ) and calcaneocuboid joint (CCJ). The combined medial and
      lateral incisions were used to obtain adequate exposure for CCJ, STJ and TNJ.
      Then the cartilages of CCJ, STJ and TNJ were completely denuded and osteotomies
      to restore their proper alignments. The optimal positioning of hindfoot could be
      achieved and fixed by Kirschner wires. Two cannulated screws of 7.3 mm were
      delivered through the plantar aspect of heel to fix STJ. And then two 4.5 mm
      cannulated screws individually fixed TNJ and CCJ distal to proximal. Clinical
      evaluations were based on the AOFAS ankle-hindfoot scale and subjective
      assessments of pains, function, cosmesis and overall satisfaction. Radiographic
      evaluations included measurements of anterior-posterior talo-first metatarsal
      angle, lateral talocalcaneal angle, lateral talo-first metatarsal angle and an
      assessment of time to union for all arthrodeses. RESULTS: All patients were
      followed-up with a mean time of 13.2 (6 - 21) months. The average AOFAS ankle
      hindfoot scale improved from 39.4 +/- 4.4 preoperatively to 83.7 +/- 2.6
      postoperatively (P < 0.01). And the patients experienced subjective improvements
      in pain, function and cosmesis. Overall, all patients were satisfied.
      Radiographically, the rate of bone healing was 100%. The anterior-posterior talo
      first metatarsal angle, lateral talocalcaneal angle and lateral talo-first
      metatarsal angle statistically improved. No complication, such as infection and
      un-union, was reported. CONCLUSION: Triple arthrodesis with osteotomy is an
      effective procedure for the treatment of stage IIB and III adult-acquired
      flatfoot deformity. It may relieve pains, correct structural deformities and
      obtain excellent clinical outcomes.

PMID- 21092488
TI  - [Classification and arthroscopic surgery of chronic achilles tendinitis].
AB  - OBJECTIVE: To investigate the clinical classification of chronic achilles
      tendinitis and analyze the surgical technique and efficacy of arthroscopic
      surgery. METHODS: Twenty-two patients (16 males, 6 females) with chronic achilles
      tendinitis were recruited. The average age was 33.5 years old (range: 17 - 53).
      Sixteen cases were caused by sport injury while 6 cases had no definite
      etiological factor. The Achilles tendinopathy was divided into three types
      according to clinical characteristics and the results of X ray, CT scan and MRI
      examination of ankle: Type 1, hypertrophy (n = 10); Type 2, calcified tubercle (n
      = 5); Type 3, fiber tear (n = 7). All cases were treated with endoscopic
      debridement of ventral neovascularized area, peritendineum and Achilles tendon by
      shaver and radiofrequency (RF) probe. RESULTS: The patients were followed-up for
      a mean of 14 months (range: 9 - 15). Evaluated by our criteria and visual
      analogue scale, the post-operative efficacy was excellent in 12 cases, good in 8
      and fair in 2. No postoperative complications, such as neurovascular injury,
      infection and rupture of Achilles tendon, was recorded. CONCLUSION: This scheme
      of classifying is helpful to the diagnosis and effective treatment of chronic
      Achilles tendonitis. With a high safety and a satisfactory efficacy, arthroscopic
      surgery has the advantages of minimally invasiveness.

PMID- 21092489
TI  - [Medial displacement calcaneal osteotomy with mini-incision for the treatment of
      acquired flexible flatfoot caused by posterior tibial tendon dysfunction].
AB  - OBJECTIVE: To investigate the clinical outcomes of medial displacement calcaneal
      osteotomy with mini-incision for the treatment of acquired flexible flatfoot
      caused by posterior tibial tendon dysfunction. METHODS: From 2005 to 2009, 10
      patients (13 feet) of acquired flexible flatfoot with obvious heel valgus
      underwent medial displacement calcaneal osteotomy with mini-incision. The lateral
      skin incision of 3.0 - 4.5cm was made to explore the lateral calcaneal wall.
      Calcaneal osteotomy was performed from inferior and lateral to superior and
      medial, perpendicular to the longitudinal axis of calcaneal body. The distal
      segment was displaced medially for 1/3-1/2 width of calcaneal body and fixed by
      two parallel cannulated screws. All patients were evaluated at 6 weeks, 3 months,
      6 months, 12 months and every 6 months pre- and post-operatively by clinical
      examinations and radiological studies. All patients were physically examined with
      an extended protocol of questionnaires and the AOFAS Ankle & Hindfoot Scales. The
      lateral view of full foot allowed an assessment of bone healing, calcaneus
      inclination angle (CI), talocalcaneal angle (TC) and talar first metatarsal angle
      (TMT). The AP view of full foot allows assessment of TC and TMT. The heel
      varus/valgus alignment could be evaluated on the axial radiographs of hindfoot.
      RESULTS: With a mean postoperative follow-up period of 20.3 months (range 7 - 55
      Ms), all patients had bone union as confirmed by clinical examination and
      radiology. The AOFAS rating scale improved from a pre-operative mean of 50.3 to a
      mean of 80.2 at 6 months and a mean of 84.2 at last follow-up, without any
      complication of infection, nerve injure and so on. All radiographic parameters
      were statistically significant (P < 0.001), including CI, TC and TMT on the
      lateral view and TC and TMT on the AP view. The heel varus/valgus was corrected
      on the axial view. CONCLUSION: The medial displacement calcaneal osteotomy with
      mini-incision is a recommended procedure for the treatment of acquired flexible
      flatfoot with excellent clinical outcomes, correction of deformity and fewer
      complications.

PMID- 21092490
TI  - [Treatment of flatfoot deformity with concurrent spinal disease in children].
AB  - OBJECTIVE: To study the curative effect of operation to flatfoot deformity with
      concurrent spinal disease in children. METHODS: A retrospective survey was
      performed in 8 flatfoot patients with concurrent spinal disease from January 2004
      to January 2008. Every case received special operative treatment. After casting,
      achilles tendon prolongation, reefing or tendon transfer, rehabilitation therapy
      was performed sequentially. Radiographs and clinical outcomes were evaluated
      during the follow-up. RESULTS: Six patients were followed up. There were 2 feet
      in 1 female and 7 feet in 5 males. The complications included tethered cord
      syndrome (n = 1), T12-S1 vertebral canal arachnoid cyst (n = 1), cerebral palsy
      and scoliosis (n = 1) and scoliosis and spinal bifida occult (n = 3). The average
      age was 8.4 (4 - 14) years old and the average follow-up time 22 (14 - 64)
      months. All cases were satisfied with the appearance and function according to
      Maryland foot score. Five were excellent, 2 good and 2 fair postoperatively
      versus 2 fair and 7 failed preoperatively. The total excellent and good rate was
      77.8%. In the early stage after tendon transfer in 4 patients, the lateral view
      of height arch, talus-first metatarsal angle, calcaneus-navicular-first
      metatarsal angle and talonavicular coverage angle improved. Yet it lost the
      improved angle and reverted to the pre-operative state. No degenerative change
      was detected in tarsus joints during the long follow-up. CONCLUSION: The special
      and sequential surgical procedure may be an effective regimen in the treatment of
      flatfoot deformity with concurrent spinal disease in children.

PMID- 21092491
TI  - [The effects of stretch sensitive positive ion channel on the high
      externalization of MUC5AC in airway epithelial cells by mechanical stretching].
AB  - OBJECTIVE: The effects of stretch sensitive positive ion channel, the internal
      flow of Ca(2+) and myristoylated alanine-rich C kinase substrate (MARCKS) on the
      high externalization of MUC5AC in airway epithelial cells in mechanical
      stretching. METHODS: Mini-type Multi-functional Bio-impact Machin was used to
      construct the model of mechanical stretching. The airway epithelial cells were
      divide into control group, stretch, stretch and gadolinium, stretch and low
      molecular weight heparin, stretch and nifedipine, stretch and the locked nucleic
      acids of MARCKS effective domain (ED), stretch and the control locked nucleic
      acids of MARCKS ED groups. The expression of MUC5AC and SNAP23 protein in cells
      were determined by immunohistochemistry method, contents of MUC5AC and SNAP23
      protein were measured by Image Pro Plus 5.0. MUC5AC protein in supernatant was
      determined by ELISA methods. SNAP23 mRNA was determined by RT-PCR methods.
      RESULTS: Mechanical stretching could increase the expression of SNAP23 and MUC5AC
      in cells and MUC5AC in supernatant (P < 0.05). Gadolinium, nifedipine and LNA of
      MARCKS ED could reduce the increase the expression of SNAP23 and MUC5AC in cells
      and MUC5AC in supernatant (all P < 0.05). CONCLUSION: Mechanical stretching could
      increase the expression of MUC5AC in airway epithelial cells. This maybe is
      concerned with stretch sensitive positive ion channel, the internal flow of
      Ca(2+) and MARCKS.

PMID- 21092492
TI  - [Management of prosthetic graft occlusion after lower extremity bypasses].
AB  - OBJECTIVE: Report the experience of management of graft occlusion in patients
      with lower extremity bypasses and discuss the appropriate treatment strategy.
      METHODS: From Oct. 2004 to Oct. 2009, 104 cases of graft occlusion were treated
      in 53 patients with lower extremity arterial bypasses, including medical therapy
      for 10 cases and redo operations for 94 cases: graft thrombectomy alone for 26
      cases, redo bypass or extension bypass with prosthetic or autologous vein grafts
      for 23 cases, graft thrombectomy plus balloon angioplasty for 18 cases, major
      amputation for 14 cases, graft thrombectomy plus femoral or popliteal artery
      endarterectomy for 10 cases, removal of occluded graft with infection for 2 case,
      and autologous stem cell transplantation for 1 case. RESULTS: 77 reconstructive
      procedures were applied and graft failures recurred in 49 cases (63.6%). One
      patient died of acute renal failure during peri-operative period and 9 patients
      died during follow-up; 6 patients were lost to follow-up. The remaining 37
      patients were followed: major amputation for 12 patients, patent grafts after
      reconstruction in 18 patients, and medical therapy after graft occlusion for 7
      patients with limb salvage. Kaplan-Meier survival analysis revealed 3-year
      survival of 77.4%, limb salvage of 64.7%, and graft patency of 45.7%. Effect of
      different procedures on cumulative patency was of no statistical significance.
      CONCLUSIONS: Graft occlusions after lower extremity bypasses may result in high
      rate of reocclusion and amputation. Optimal management should be based on a
      thorough analysis of individual condition.

PMID- 21092493
TI  - [Management of patients with iatrogenic pseudoaneurysm of carotid and vertebral
      artery].
AB  - OBJECTIVE: To evaluate the formation mechanism and management of iatrogenic
      pseudoaneurysms of carotid and vertebral artery. METHODS: Four patients with
      iatrogenic pseudoaneurysms were identified at our department from April 2004 to
      February 2009. One was caused by radiotherapy and the others due to surgical
      trauma. Two parents were treated with balloon occlusion of parent artery. Stent
      grafts were deployed in the other two patients to ensure the patency of parent
      arteries and occlusion of pseudoaneurysm. RESULTS: One patient with
      pseudoaneurysm of internal carotid artery developed decompensation after balloon
      occlusion. Unfortunately, long-term paralysis occurred after decompressive
      craniectomy. The other patients with vertebral artery pseudoaneurysm achieved an
      excellent outcome after balloon occlusion. The therapeutic effect of stent grafts
      in two internal carotid artery pseudoaneurysms was achieved. No recurrence was
      found during a post-operative follow-up of 15 months to 6 years. CONCLUSION:
      Iatrogenic pseudoaneurysms of carotid and vertebral artery deserve a priority
      attention. Cerebrovascular angiography should be performed if needed. The
      neurosurgical intervention for iatrogenic pseudoaneurysms may yield an excellent
      outcome.

PMID- 21092494
TI  - [Minimally invasive neurosurgery for removal of pituitary adenomas by
      neuroendoscope aided with sellar floor reconstruction].
AB  - OBJECTIVE: To evaluate the effect of surgical technique and clinical curative
      effect for a unilateral endonasal-transsphenoidal approach in the removal of
      pituitary adenomas (PAs) by an endoscope-assisted technique with sellar floor
      reconstruction. METHODS: Between April 2001 and March 2009, 426 consecutive
      patients underwent extended neuroendoscopic unilateral endonasal transsphenoidal
      surgery. The series consisted of 54 (12.7%) as I type of Pas and 105 (24.6%) II
      type, 181(42.5%) III type and 86 (20.2%) IV type according to Hardy's
      classification criteria of pituitary adenoma. RESULTS: Tumor removal, as assessed
      by intraoperative findings and postoperative magnetic resonance imaging or CT
      scans, revealed complete tumor removal in 370 cases (86.9%) and subtotal tumor
      removal in 32 cases (7.5%) were achieved. Partial removal was carried out in the
      remaining 24 cases (5.6%) with fibrous tumor. Three patients (0.7%) had
      postoperative death in this group. Twenty-four patients (5.6%) had a
      postoperative cerebrospinal fluid leak that required repair operations. Six
      patients (1.4%) experienced a sphenoid mucositis and meningitis and they were
      cured by medical therapy. CONCLUSION: The slightly soft texture of PAs with or
      without a limited suprasellar extension and without involvement of vascular
      structures, may be resected through such an extended neuroendoscopic
      transsphenoidal approach. Intraoperative angled endoscope is a useful adjunct for
      safe removals.

PMID- 21092495
TI  - [Surgical treatment of giant intracranial arteriovenous malformations].
AB  - OBJECTIVE: To review surgical outcomes in treating intracranial Giant
      arteriovenous malformations (AVMs). To find out the prognosis factors of surgical
      treatment. METHODS: We collected 46 consecutive cases of giant AVMs treated at
      Beijing Tiantan Hospital, reviewed the radiological and Spetzler-Martin grading.
      25 of the patients selected were male (54%), and 21 were female (46%), with a
      mean age of 30.6. The major presenting symptoms were seizures, headaches,
      hemorrhage and neurological deficits. According to the Spetzler-Martin Grading, 8
      patients were Grade III, 22 were Grade IV, and 16 were Grade V. All patients
      received surgical treatment and postoperative DSA were performed. Clinical
      results and long term follow-up (KPS) were gathered for analysis. RESULTS: One of
      the 35 patients who received postoperative DSA revealed residual AVMs. Among all
      patients, severe complications were observed in 9 patients, and 1 patient died in
      the hospital. Complications included hemiparalysis (15 cases), aphasia (6 cases),
      hemianopia (9 cases), cranial nerve dysfunction (5 cases), and seizure (5 cases).
      Normal perfusion pressure breakthrough (NPPB) was observed in 6 patients. After 6
      - 108 months of follow-up, 33 of 37 survived follow-up patients presented normal
      function or minimal symptoms and ability to work or study, 4 patients died (2
      were surgical-related). CONCLUSION: Pre-surgical evaluation of every candidates
      and treatment choice are the determining factors in giant AVMs therapy.
      Microsurgery remains one of the most effective ways for eliminating giant
      cerebral AVMs, and the complication rate was acceptable. For giant cerebral AVMs
      located superficially or do not involve critical components, a good outcome can
      be expected through surgical resection.

PMID- 21092496
TI  - [Microsurgical management of tuberculum sellae meningiomas].
AB  - OBJECTIVE: To explore the approach and efficacy of microsurgery for tuberculum
      sellae meningiomas. METHODS: The clinical data of 56 patients with tuberculum
      sellae meningiomas treated at our department from 1991 - 2009 were analyzed
      retrospectively. There were 20 males and 36 females with an age range of 32 - 65
      years old (mean: 46). All patients underwent microsurgery through pterional,
      unilateral subfrontal, orbitozygomatic or supraorbital keyhole approach. RESULTS:
      Among these patients, there were total resection (n = 51) and subtotal resection
      (n = 5). Postoperatively, 53 patients recovered well, 2 had a mild disability, 1
      suffered a severe disability and there was no mortality. CONCLUSION: Most cases
      of tuberculum sellae meningiomas can be removed safely and totally. Several
      approaches may be employed to achieve the best outcomes. Microsurgery can
      markedly boost the total resection rate of tuberculum salle meningiomas and lower
      the postoperative complications and mortality.

PMID- 21092497
TI  - [Fertilizing ability, cleavage potential and inheritance risk of
      globozoospermia].
AB  - OBJECTIVE: To explore the fertilizing ability, cleavage potential and inheritance
      risks of globozoospermia. METHODS: A globozoospermic patient was diagnosed by
      sperm morphological staining and transmission electron microscope. From his wife
      the investigators obtained 26 oocytes in which 6 oocytes were donated and the
      other 19 (in 20) MII oocytes injected into 19 round-headed sperms. Six donated
      oocytes accepted in vitro fertilization (IVF). This patient's chromosome and
      microdeletion in AZFa, AZFb and AZFc in Y chromosome were checked through 6
      sequence tag sites of sY84, sY86, sY127, sY134, sY254 and sY255. RESULTS: Only 4
      (in 19) were normally fertilized and cleaved. All 6 donated oocytes were normally
      fertilized and cleaved. The fertilizing rate was significantly higher than that
      of this patient (100% vs 21.1%, P < 0.01). But the cleavage rate has no
      statistical difference (100% vs 100%, P > 0.05). This patient had normal
      chromosome (46, XY) and there was no deletion in Y chromosome. His wife became
      pregnant after accepting two thawed embryos and then gave birth to a boy whose
      chromosome was normal (46, XY). The acceptor also gave birth to a healthy boy
      after accepting two thawed embryos. CONCLUSIONS: Despite a lower fertilizing
      rate, intracytoplasmic sperm injection is still an effective therapy for
      globozoospermic infertility.

PMID- 21092498
TI  - [Evaluation of different ultrasonic modalities for prenatal screening congenital
      heart diseases].
AB  - OBJECTIVE: To evaluate the value of four chamber view, outflow tract view and
      color Doppler echocardiography for detecting the fetal congenital heart defects
      among high-risk populations. And to discuss the significance of screening
      congenital heart defects by three methods and select the suitable method for
      wider applications. METHODS: The echocardiographic records of all pregnant women
      performed at our hospital from January 2006 to December 2007 were reviewed
      retrospectively by screening of clinical epidemiology. All cases received
      ultrasonic examinations. The abnormal cases with postnatal confirmation by
      echocardiogram or autopsy were included. The abnormalities detected in each view
      were analyzed and classified. RESULTS: A total of 52 fetuses with congenital
      heart defects were detected by gray scale sonography and color Doppler sonography
      in 1310 cases. Each specific cardiac defect had its typical finding in these
      three planes. The sensitivities of three methods were 61.5%, 88.5% and 96.1%
      respectively. CONCLUSION: Four chamber view, outflow tract view and color Doppler
      sonography have played an important role in screening fetal common congenital
      heart defects. Outflow tract view is easy to operate and it may be recommended as
      a suitable method.

PMID- 21092499
TI  - [Cardiac valve involvement in Behcet's disease: a clinical study of 10 patients].
AB  - OBJECTIVE: To assess the clinical features in patients with cardiac valve lesions
      associated with Behcet's disease (BD). METHODS: We retrospectively reviewed the
      clinical data of 10 BD patients with cardiac valve lesions who were admitted to
      Peking Union Medical College Hospital (PUMCH) during June 1999 to June 2009.
      RESULTS: Aortic regurgitation occurred in 6% of patients with BD in PUCMH.
      Patients included 8 male and 2 female with the mean age of 36.5. All the patients
      had occult onset cardiac symptoms with an average length of clinical course of 6
      years. 5 patients fulfilled the ISG diagnostic criteria for BD and another 5
      patients diagnosed by experts. The main echocardiography findings were severe
      aortic regurgitation, aneurysmal dilatations of ascendant aorta, echo-free space
      at the aortic root, aortic valve prolapse, mesh like mass incorporating aortic
      cusp, aortic valve perforation, et al. 3 patients underwent 7 operations. 5
      simple aortic valve replacement (AVR) surgeries resulted in severe perivalvular
      leakage. 2 patients underwent Bentall and heart transplant surgeries respectively
      with perioperative immunosuppressive therapy had no complications. CONCLUSION:
      Cardiac valve involvement in BD is a rare but critical problem that requires a
      timely diagnosis and management. The current diagnostic criteria may have
      possibilities of delayed diagnosis of such problem. Echocardiography seems to be
      helpful for the timely diagnosis. The immunosuppressive therapy and Bentall type
      operations may be essential for improving the treatment outcome of BD with
      cardiac valve lesions.

PMID- 21092500
TI  - [Comparing the analgesic efficacy of continuous femoral nerve blockade and
      continuous intravenous analgesia after total knee arthroplasty].
AB  - OBJECTIVE: To compare the analgesic efficacy of continuous femoral nerve blockade
      (CFNB) and continuous intravenous analgesia (CIA) after total knee arthroplasty
      (TKA). METHODS: 126 patients undergoing TKA under combined epidural-spinal
      anesthesia were randomized to receive either a femoral infusion of ropivacaine
      0.2% (median infusion rate 5 ml/h) (n = 63) or an intravenous infusion of
      fentanyl 30 ug/kg (2 ml/h) (n = 63). Adjuvant analgesics were oral celebrex or IM
      pethidine. In the CFNB group, CFNB was established before combined epidural
      spinal anesthesia and 20 ml 0.5%ropivacaine was infused through the catheter
      placed near femoral nerve. Visual analogue scale (VAS) scores were assessed at
      rest and on passive mobilization by acute pain service blinded to analgesic
      treatment. Nausea and vomiting, dizziness, satisfaction and other side-effects
      were assessed postoperatively. RESULTS: There was significantly less VAS scores
      in the CFNB group comparing the CIA group at rest 4, 8, 12, 16, 24, 36, 48 h
      after surgery (P < 0.01). A significant difference in VAS scores was found in
      CFNB group vs CIA group on passive mobilization 24, 36, 48 h after operation (P <
      0.01). There was significantly less dizziness, nausea and vomiting in the CFNB
      group (P < 0.01). Patient satisfaction was higher in the CFNB group (92.1%) than
      the CIA group (20.6%) (P < 0.01). CONCLUSION: CFNA with ropivacaine 0.2% is more
      effective in controlling postoperative pain than CIA and CFNB is an effective
      regional component of a multimodal analgesic strategy after TKA.

PMID- 21092501
TI  - [Selective innervation of sacral anterior rootlets to micturition and erection
      function in rats].
AB  - OBJECTIVE: To investigate the selective innervation of sacral anterior rootlets
      to micturition and erection function in SD rats. METHODS: Forty male SD rats of
      clean grade, aged 6 weeks old, were selected. Ten rats received a retrograde
      nerve tract tracing study. Thirty rats were chosen for an electro-physiological
      study. The L6, S1 spinal cord segment anterior rootlets of anesthetic rats were
      electrostimulated respectively. The intravesical pressure, urethral perfusion
      pressure and intracavernous pressure were recorded simultaneously and innervation
      effectiveness was analyzed. RESULTS: CB-HRP labeled neurons were observed mainly
      in L6 and S1 spinal cords. When some anterior rootlets of L6 and S1 were
      electrostimulated, the intravesical pressure rose gradually, but the urethral
      perfusion pressure and the intracavernous pressure curve changed slightly; when
      other rootlets of the same anterior root were stimulated, the urethral perfusion
      pressure could reach the peak; while others were stimulated, the intracavernous
      pressure rose quickly, but there were no great changes in intravesical pressure
      and urethral perfusion pressure. Some other rootlets might lead to the
      simultaneous changes of 2 or 3 above-mentioned pressures. CONCLUSION: The
      innervations of L6 and S1 anterior rootlets to rats' bladder detrusor, external
      urethral sphincter and penile cavernous body are significantly distinct.
      Different rootlets may be distinguished by microanatomy and electrostimulation.

PMID- 21092502
TI  - [In vivo imaging analysis of biodistribution of FITC-labeled Rituximab in
      lymphoma-bearing nude mice].
AB  - OBJECTIVE: To conduct an in vivo optical imaging analysis of the biodistribution
      of antibody Rituximab in lymphoma tumor-bearing nude mice. METHODS: Laser
      scanning confocal microscope and flow cytometry were employed to determine the
      affinity of FITC-labeled Rituximab (FITC-Rituximab) with human lymphoma Raji
      cells. And the in vivo optical imaging system was used to analyze the
      biodistribution of FITC-Rituximab in lymphoma-transplanted xenograft nude mice.
      RESULTS: The results of flow cytometry and laser scanning confocal microscope
      demonstrated that FITC-Rituximab had remarkable affinity with lymphoma Raji cells
      and was mainly bound at cell membrane. The results of in vivo imaging analysis
      suggested that FITC-Rituximab could specifically accumulated at peritumor tissue
      less than 1 h, then penetrated into the interior of tumor and concentrated in 3-4
      h. And the specific concentration of FITC-Rituximab could still been observed
      more than 8-10 h whereas there was no apparent fluorescence at other tissues.
      Furthermore, the results observed from a two-flank tumor xenograft model showed
      that FITC-Rituximab possessed specific binding affinity for CD20-overexpressed
      lymphoma. CONCLUSION: The in vivo optical imaging system can accurately monitor
      the distribution of FITC-Rituximab in tumor-bearing nude mice. And this technique
      has a reference value and significance for a real-time analysis of tumor
      targeting capability of antibody drugs.

PMID- 21092503
TI  - [Attach importance to the methods and strategies for lymphadenectomy in gastric
      cancer surgery].

PMID- 21092504
TI  - [Impact of timing of intervention on prognosis of non-ST segment elevation acute
      coronary syndrome patients with renal dysfunction].
AB  - OBJECTIVE: To investigate the effects of intervention treatment in relation to
      renal function in patients with non-ST segment elevation acute coronary syndrome
      (NSTEACS). METHODS: A total of 815 NSTEACS patients were randomized to receive
      either early intervention (coronary angiography within 24 h of randomization) or
      delayed intervention (coronary angiography over 36 h after randomization). Serum
      creatinine was determined in 781 patients at admission and glomerular filtration
      rate (eGFR) calculated by the abbreviated MDRD formula. The subjects were
      stratified according to eGFR>=90 ml*min(-1).(1.73 m2)(-1), 60<=eGFR<90 ml*min(
      1).(1.73 m2)(-1) and eGFR<60 ml*min(-1).(1.73 m2)(-1) and followed up for 180
      days. Death, myocardial infarction or stroke was regarded as the primary end
      point. RESULTS: Incidence of the primary end point was 6.3% at eGFR>=90 ml*min(
      1)(1.73 m2)(-1), 10.1% at 60<=eGFR<90 ml*min(-1).(1.73 m2)(-1) and 15.5% at
      eGFR<60 ml*min(-1).(1.73 m2)(-1) (P=0.032). The 180 day mortality was 1.9% at
      eGFR>=90 ml*min(-1) (1.73 m2)(-1), 2.6% at 60<=eGFR<90 ml*min(-1).(1.73 m2)(-1)
      and 9.1% at eGFR<60 ml*min(-1).(1.73 m2)(-1) (P=0.01). In a logistic regression
      analysis, adjusting for other important covariables, the delayed intervention
      remained independently associated with the risk of primary end point in
      60<=eGFR<90 ml*min(-1).(1.73 m2)(-1) group (odds ratio, 2.106 ; 95% confidence
      interval, 1.102-4.024). CONCLUSION: The strategy of early intervention reduces
      the risk of death/MI or stroke at 180 days in NSTEACS patients with mild renal
      dysfunction.

PMID- 21092505
TI  - [Surgical treatment and prognostic analysis of retroperitoneal paragangliomas: a
      study of 19 cases].
AB  - OBJECTIVE: To investigate the clinical characteristics, surgical treatment and
      prognostic analysis of retroperitoneal paragangliomas and to enhance the
      diagnostic and therapeutic levels of retroperitoneal paragangliomas. METHODS: The
      clinical data of all patients undergoing paraganglioma resection at our
      department from November 1999 to March 2009 were retrospectively analyzed. The
      parameters included clinical manifestations, tumor function, surgical findings,
      operative approach, tumor pathology, imaging study and post-operative survival
      time. RESULTS: (1) The ratio of male to female was 1.375:1 and the median age 50
      years old. The most common presenting symptom was abdominal mass (9/19, 47%). And
      the preoperative CT misdiagnosis rate was high (89%). (2) The most common tumor
      location was periaortic and percival (9/19, 47%). The average maximal diameter of
      tumors was 8.6 cm. 58% (11/19) tumors had integral peplow, 42% (8/19) adhered to
      adjacent organs and 26% (5/19) required adjacent organ resection. (3) The rate of
      functional tumor was 63% (12/19). Preoperative and intra-operative hypertension
      occurred in 67% (8/12) and 33% (4/12) respectively. (4) Immunohistochemical
      staining was performed in 18 tumors of 16 patients. Among all tumors, 89% (16/18)
      showed positive immunoreactivity for chromogranin and 67% (12/18) for S-100. PCNA
      staining showed different proliferative activities (0%-48% positive). Only
      malignant tumors showed positive immunoreactivity for Ki-67 staining and P53
      staining (20% & 34% respectively). (5) The overall 5-year survival was 77%.
      Survival was significantly worse after metastasis (chi2=6.604, P=0.01). But it
      was not dependent on tumor diameter (chi2=3.208, P=0.201), the secreting function
      of tumor (chi2=0.121, P=0.728) and the status of tumor margins (chi2=0.036,
      P=0.849). CONCLUSION: It is difficult to make an early diagnosis of
      retroperitoneal paragangliomas. Survival is significantly worse after metastasis.
      Lifelong follow-up for recurrence is important. And it is absolutely essential to
      perform immunohistochemical staining for tumors.

PMID- 21092506
TI  - [Clinical significance of toll-like receptor 4 expression on the surface of
      peripheral blood mononuclear cells in uremic patients].
AB  - OBJECTIVE: To explore the clinical significance of toll-like receptor 4
      expression on the surface of peripheral blood mononuclear cells (PBMC) in uremic
      patients and observe the effect of ultrapure dialysate on the PBMC expression of
      TLR4 in these patients. METHODS: Eighty patients on maintenance dialysis were
      randomly divided into two groups: conventional dialysate group (CD, n=40),
      ultrapure dialysate group (UPD, n=40) and 40 uremic patients without dialysis in
      NHD group. The blood cells from all patients and 40 healthy controls were stained
      with FITC labeling anti-TLR4 monoclonal antibodies. Samples were collected and
      analyzed by flow cytometry. RESULTS: The expression of TLR4 was significantly
      lower in CD group (18.1+/-3.7) than in NHD group (24.5+/-4.6, P<0.05) and healthy
      control group (31.6+/-5.8, P<0.01). And marked difference existed between CD
      group (18.1+/-3.7) and UPD group (23.1+/-3.2, P<0.05) at Month 6 post-dialysis.
      In CD group the expression of TLR4 became significantly smaller as the duration
      of dialysis increased (P<0.05) while in UPD group although the expression of TLR4
      became smaller as the duration of dialysis became longer. But the difference was
      not statistically significant (P>0.05). CONCLUSION: The PBMC expression of TLR4
      becomes down-regulated in uremic patients with or without dialysis and its
      expression is smaller in conventional dialysate group than in ultrapure dialysate
      group. The conventional dialysate may suppress the expression of TLR4 while the
      phenomenon is absent in ultrapure dialysate group.

PMID- 21092507
TI  - [Risk factors of novel severe influenza A(H1N1) with concurrent adult respiratory
      distress syndrome].
AB  - OBJECTIVE: To analyze the risk factors of novel severe influenza A (H1N1) with
      concurrent adult respiratory distress syndrome (ARDS). METHODS: A multivariable
      Logistic regression analysis was conducted for ARDS risk factors in controlled
      clinical trials for comparing the clinical features between the ARDS and non-ARDS
      groups and comparing ARDS patients' lymphocyte counts and T lymphocyte subsets
      between the smoking and non-smoking groups through a retrospective analysis of 92
      novel influenza A (H1N1) patients who admitted to our hospital from October 2009
      to January 2010. RESULTS: Through a single factor analysis between ARDS and non
      ARDS groups, the comparisons in the factors including smoking (17 cases vs 11
      cases), T lymphocyte subsets, lactate dehydrogenase (LDH), initial treatment
      point of oseltamivir and initial oxygen flow greater than 2 L/min (28 cases vs 18
      cases) had statistically significant differences (all P<0.05). The comparison in
      T lymphocyte subsets had statistically significant difference between the smoking
      and non-smoking groups in ARDS patients (all P<0.05). The multivariable Logistic
      regression analysis showed that smoking (P=0.027, OR=8.05, 95%CI: 1.28-50.80) and
      initial oxygen flow greater than 2 L/min (P=0.010, OR=16.70, 95%CI: 3.29-84.84)
      were relevant to the incidence of ARDS in novel influenza A (H1N1) patients.
      CONCLUSION: Smoking and initial oxygen flow greater than 2 L/min were the risk
      factors of novel severe influenza A (H1N1) with concurrent ARDS.

PMID- 21092508
TI  - [Diagnostic value of reflux disease questionnaires in children with
      gastroesophageal reflux disease].
AB  - OBJECTIVE: To evaluate the value of reflux diagnostic questionnaire in the
      diagnosis of children with gastroesophageal reflux disease (GERD). METHODS: Forty
      five children aged 7-16 years old referred for suspected GERD with
      vomiting/regurgitation, nausea, heartburn/retrosternal pain, abdominal pain,
      epigastric pain, acid regurgitation and pain while swallowing were assessed. Each
      symptom was rated from 0 to 3 according to its severity and frequency. The items
      of questionnaire were validated against the results from upper gastrointestinal
      endoscopy and esophageal 24 h pH monitoring. And the results were compared with
      symptom scores to determine the threshold value for GERD. RESULTS: In 45
      patients, the ratio of male to female was 1.37:1 and the mean age (11.1+/-2.6)
      years old. Composite score in 23 patients with GERD (20+/-10) was significantly
      higher than that in 22 patients without GERD (13+/-4) (P<0.05). There was no
      significant difference of composite scores among patients with grades 0, I, II
      and III according to upper gastrointestinal endoscopy (P>0.05). With 13.0 as
      threshold score for GERD, the sum of sensitivity and specificity was maximal. The
      area under the receiver operating characteristic curve (ROC) was 0.79 while true
      positive diagnostic rate 72.0% and true negative diagnostic rate 75.0% with a
      sensitivity of 78.3%, a specificity of 68.2% and an accuracy of 73.3%.
      CONCLUSION: Reflux diagnostic questionnaire is a suitable method in initial
      diagnosis of GERD. It may serve as a screening test for GERD in 7-16-year-old
      children.

PMID- 21092509
TI  - [Surgical treatment of acute pulmonary embolism].
AB  - OBJECTIVE: To evaluate the clinical value of surgical treatment for acute
      pulmonary embolism under shallow low temperature cardiopulmonary bypass. METHODS:
      From April 2004 to October 2009, the data of 12 inpatients with acute pulmonary
      embolism were analyzed. Deep vein thrombosis was present in all patients. There
      were unilateral pulmonary embolism (n=7), bilateral pulmonary embolism (n=5),
      shock (n=5); heart function class III (n=7) and heart function class IV (n=5).
      The average time from onset to surgery was 9 hours. RESULTS: Among all cases, no
      recurrence was observed. All showed normal heart function and fully resumed
      manual labor. CONCLUSION: Surgical thrombectomy for acute pulmonary embolism has
      an excellent clinical efficacy. Its routine use should be encouraged.

PMID- 21092510
TI  - [Insulin-like growth factor 1 regulates expression of stem cell factor through
      ERKMAPK signaling pathway in gastric smooth muscle cell].
AB  - OBJECTIVE: To explore the effect and the intracellular signal transduction
      pathway of insulin-like growth factor 1 (IGF-1) on the expression of stem cell
      factor (SCF) in gastric smooth muscle cells (SMC). METHODS: Gastric SMC from SD
      rats were cultured by enzymolysis and identified by alpha-actin
      immunofluorescence methods. Western blot and quantitative reverse transcription
      polymerase chain reaction were used to examine the expression of SCF in gastric
      SMC:(1) The level of SCF after gastric SMC were cultured with IGF-1. (2) The
      level of SCF after IGF-1 receptor (IGF-1Ralpha) monoclonal antibody were added.
      (3) Another SMC were pretreated with specific mitogen-activated protein kinase
      (MEK) inhibitor PD-98059 and phosphatidylinositol 3-kinase (PI 3-kinase)
      inhibitor LY-294002, and investigate expression of SCF in gastric SMC. RESULTS: A
      very low level of SCF was expressed in gastric SMC cultured in bovine serum free
      medium. A low concentration of IGF-1 (5 and 10 ug/L) had no effect on the
      expression of SCF (both P>0.05), but the expressions of SCF mRNA and protein
      increased in IGF-1 at a higher concentration (50, 100 and 150 ug/L) (2.79, 5.51
      and 5.35-fold in protein respectively, 1.81, 2.54 and 2.38-fold in mRNA
      respectively, all P<0.05), and IGF-1 in 100 ug/L may be the effective final
      concentration (all P<0.05). The peak of SCF increment was at the 16th hour with
      IGF-1 (2.36-fold in protein, 5.51-fold in mRNA, all P<0.05). The expression of
      SCF could be inhibited by IGF-1 receptor monoclonal antibody in a dose-dependent
      manner (all P<0.05). The IGF-1-induced SCF expression was reduced significantly
      by a pretreatment of PD-98059 (23% in protein and 48% in mRNA, P<0.05). And LY
      294002 had no effect on the expression of SCF (P>0.05). CONCLUSION: The SCF
      expression in gastric SMC is stimulated by IGF-1 in both dose- and time-dependent
      manners through IGF-1R in which ERKMAPK signal transduction may play an important
      role.

PMID- 21092512
TI  - [Mechanical properties of thermoplastic materials].
AB  - OBJECTIVE: To investigate the mechanical properties of various brands of
      thermoplastic materials under different test conditions so as to analyze their
      influencing factors so as to provide a reference for improving the effect of
      invisible orthodontics. METHODS: Three brands of thermoplastic materials, DR,
      Biolon and Erkodent, were selected. They were tested by Instron testing machine
      to measure their maximal stress and modulus under different processing modes,
      including pre-thermoforming, post-thermoforming and dipped in artificial saliva
      for two weeks after thermoforming. The data were analyzed by SPSS 11.5. Analyzed
      the mechanical properties change-trend under each test condition. RESULTS: The
      modulus (MPa) and maximum stress (MPa) of control group were significantly higher
      than those of thermoforming group (DR: 9.63+/-0.68 vs 7.85+/-0.61, 267+/-8 vs
      199+/-6; Erkodent: 8.28+/-0.28 vs 7.59+/-0.45, 226+/-6 vs 199+/-6; Biolon: 8.85+/
      0.41 vs 7.07+/-0.22, 237+/-6 vs 169+/-7, all P<0.05). The modulus (MPa) and
      maximum stress (MPa) of thermoforming group were significantly lower than those
      of saliva immersion group (DR: 7.85+/-0.61 vs 9.14+/-0.41, 199+/-6 vs 243+/-7;
      Erkodent: 7.59 +/- 0.45 vs 8.38+/-0.29, 199+/-6 vs 212+/-7; Biolon: 7.07+/-0.22
      vs 7.90+/-0.31, 169+/-7 vs 197+/-5, all P<0.05). CONCLUSIONS: The different
      brands of thermoplastic materials have different mechanical properties. The
      different processing modes influence the mechanical properties of thermoplastic
      materials. The mechanical properties decrease after thermoforming and increase
      after saliva immersion.

PMID- 21092511
TI  - [Beneficial effects of retinoic acid on in vitro invasiveness of human thyroid
      carcinoma cell lines].
AB  - OBJECTIVE: To investigate the anti metastatic potential of retinoic acid as an
      important determinant of metastatic behavior in thyroid carcinoma and understand
      the role of invasion associated proteins. METHODS: Differentiated thyroid
      carcinoma cell lines FTC-133 and XTC.UC1, anaplastic thyroid cancer cell lines
      C643 and HTH74 were studied. All cell lines were cultured with all-trans-RA
      (ATRA) or solvent ethanol. The in vitro invasion and adhesion potency were
      studied by transwell experiment and short-term adhesion assay. The functions of
      invasion associated proteins, urokinase type plasminogen activator (uPA), uPA
      receptor (uPAR), MMP2 and E-cadherin were investigated by semi-quantitative RT
      PCR and Western blot. RESULTS: In vitro invasion assay revealed that ATRA
      treatment could reduce the invasive potency in all the thyroid cancer cell lines.
      On Day 5 of ATRA treatment, the numbers of cells that migrated through
      extracellular matrix were as follows, in contrast to control group, FTC-133: 91+/
      9 vs 118+/-10, C643: 92+/-17 vs 164+/-21, HTH74: 87+/-18 vs 169+/-15, and
      XTC.UC1: 95+/-23 vs 136+/-15, respectively (all P<0.05). Short term adhesion
      assay suggested that ATRA increases cancer cell adhesion to extracellular matrix
      (ECM) in C643, HTH74 and XTC.UC1. RT-PCR and Western blot both revealed
      diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74
      cell lines, the expression of uPA was reduced and the expression of E-Cadherin
      was increased; whereas the MMP2 expression was not significantly down-regulated
      in ATRA treated group. In ATRA treated FTC-133 and XTC.UC1 cell lines, MMP2
      expression was decreased, but no significant changes in uPA and E-Cadherin
      expression were observed. CONCLUSION: The present study demonstrates the
      influence of ATRA on two important determinants of metastatic behavior ("de
      adhesion" and proteolysis) in thyroid carcinoma cell lines.

PMID- 21092513
TI  - [Altered expression of intestinal cytokines in development of postinfectious
      irritable bowel syndrome mouse model].
AB  - OBJECTIVE: To observe the expression of Th1 type cytokine IL-12 and Th2 type
      cytokine IL-4 in different development phases of postinfectious irritable bowel
      syndrome in mouse model. METHODS: Mice were infected by Trichinella spiralis (350
      400 Trichinella) and weighted weekly after infection. Visceral sensitivity of
      colorectal distention in mice was assessed by abdominal withdrawal reflex (AWR)
      at Weeks 0, 2, 4, 8, 12 post-infection. Tissues of terminal ileum were collected.
      Histological pathology and inflammation were evaluated by HE staining. RESULTS:
      The weights of mice in 2 and 4-week groups were lower than those in the control
      group [(31.1+/-3.7) g vs (35.6+/-2.7) g, (36.1+/-3.4) g vs (39.8+/-2.7) g, all
      P<0.05)]. The weights of 8, 12-week groups had no statistical difference with the
      control group (all P>0.05). Severe intestinal inflammation was observed at Week 2
      during acute infectious period, but after a 4-week infection it recovered from
      intestinal inflammation, until Weeks 8-12, there was no difference with the
      control group. At 30, 45, 60 mm Hg, the AWR scores of the infectious group was
      higher than those in the control group. The 2-week group was the highest (2.60+/
      0.55 vs 1.00+/-0.35, 2.90+/-0.20 vs 1.50+/-0.70, 3.30+/-0.50 vs 2.00+/-0.35, all
      P<0.05). Mice infected at Week 8 could serve as a successful model of
      postinfectious irritable bowel syndrome. An elevated expression of IL-12, IL-4
      mRNA and protein was observed in ileocecum at Week 2 during acute phase (0.77+/
      0.04 and 0.40+/-0.05, 0.42+/-0.04 and 0.33+/-0.05), decreased expression of IL-4
      mRNA and protein was observed in ileocecum at Weeks 8, 12 (0.10+/-0.03 and 0.08+/
      0.03, 0.08+/-0.03 and 0.06+/-0.03). However a prolonged high expression of IL-12
      mRNA and protein was observed in ileocecum at Weeks 8, 12 (0.42+/-0.03 and 0.25+/
      0.05, 0.39+/-0.02 and 0.24+/-0.04), but lower than those in the 2-week group (all
      P<0.05). CONCLUSION: A differential expression of Th type cytokines is observed
      in different development phases of postinfectious irritable bowel syndrome in a
      mouse model. All cytokines increase during acute infection stage; However Th1
      type cytokine increases continuously while Th2 type cytokine decreases in the
      established model.

PMID- 21092514
TI  - [Effect of ambroxol on lung development of rat models with nitrofen-induced
      congenital diaphragmatic hernia].
AB  - OBJECTIVE: To investigate the effects of ambroxol on rat models with nitrofen
      induced congenital diaphragmatic hernia (CDH) and its potential mechanism.
      METHODS: Nine pregnant female SD rats were randomly divided into 3 groups at Day
      9.5: 2 ml olive oil intragastrically in control group (2 rats) and 200 mg
      nitrofen in nitrofen (2 rats) and ambroxol groups (5 rats). Antenatal ambroxol
      was given intraperitoneally to ambroxol group at Days 18.5, 19.5 and 20.5 of
      gestation while control and nitrofen groups only received intraperitoneal normal
      saline. At Day 21.5 the fetuses were delivered by cesarean section. Incidence of
      hernia, lung weight/body weight (LW/BW), mean terminal branch density (MTBD),
      percentage of lung alveolar area (PLAA), percentage of wall thickness (MT%) and
      the expression of TGF-beta1 were observed. RESULTS: There were 19 CDH fetuses in
      nitrofen group (68.4%). The incidence of hernia in ambroxol group was 65.1%
      (28/43). There was no significant difference (P>0.05) between two groups. LW/BW
      and PLAA decreased while MTBD and MT% increased significantly in the nitrofen
      group versus the control group [(45+/-6) mg/g vs (60+/-7) mg/g, (50.1+/-4.0)% vs
      (58.4+/-3.0)%, (14.0+/-1.8) vs (8.5+/-1.1), (45+/-6)% vs (29+/-6)%, all P=0.001].
      After ambroxol intervention, the ambroxol group showed a higher PLAA but a lower
      MTBD and MT% [(54.0+/-2.0)%, (12.2+/-2.1), (39+/-4)%] than those in the nitrofen
      group (P=0.001, 0.006, 0.002). The expression of TGF-beta1 in pulmonary tissues
      of the nitrofen group was significantly higher than that in the control group
      (13,594+/-3113 vs 9447+/-1355, P=0.001). It decreased after ambroxol intervention
      (10 015+/-818, P=0.01). CONCLUSION: Though with no effect upon the occurrence of
      CDH in rats, the administration of ambroxol may improve the pulmonary maturity.
      The down-regulated expression of TGF-beta1 and the oxidative stability are
      possible mechanisms.

PMID- 21092515
TI  - [Effect of FAM172A protein on apoptosis and proliferation in HEK293 cells].
AB  - OBJECTIVE: To study the effect of FAM172A protein related to diabetic
      macroangiopathy on apoptosis and proliferation in HEK293 cells. METHODS: The
      pDrive-FAM172A plasmid constructed in our previous study was used as a template
      to amplify human FAM172A open reading frame by a polymerase chain reaction. The
      resulting PCR products were subcloned into the eukaryotic expression vector
      PDC315 to construct recombinant PDC315-FAM172A plasmid. PDC315-FAM172A plasmid
      was identified by enzyme cleavage and sequencing analysis. HEK293 cells were
      transiently transfected respectively with appropriate PDC315 or PDC315-FAM172A
      plasmid by Lipofectamine 2000 according to the manufacturer's instruction. XTT
      assay and growth curve were used to observe the effect of over-expression of
      FAM172A gene on HEK293 cell proliferation. PI and Annexin V/PI staining method
      were used to assess the effect of FAM172A gene on apoptosis and cell cycle of
      HEK293 cell. RESULTS: Eukaryotic expression vector PDC315-FAM172A was
      successfully constructed and identified by enzyme cleavage and sequencing
      analysis. Compared with PDC315 plasmid transfection, the XTT assay showed that
      optical density (A) value increased by 52% when transfected with PDC315-FAM172A
      plasmid (0.21+/-0.07 vs 0.32+/-0.06, P<0.01). Growth curve revealed that HEK293
      cells transfected with PDC315-FAM172A plasmid proliferated faster than those
      transfected with PDC315 plasmid. PI staining showed that, as compared with PDC315
      plasmid transfection, the apoptotic rate of HEK293 cells transfected with PDC315
      FAM172A plasmid decreased by 38.5% (23.79+/-1.36 vs 14.64+/-0.95, P<0.01), cell
      percentage of G0-G1 phases significantly decreased (66.79+/-1.73 vs 58.16+/-0.75,
      P<0.01) and cell percentage of S phases significantly increased (22.62+/-1.16 vs
      33.56+/-0.94, P<0.01). Annexin V/PI staining revealed that, as compared with
      PDC315 plasmid transfection, the percentage of early and advanced apoptotic cells
      decreased by 28% (13.63+/-0.56 vs 9.79+/-0.39, P<0.01) and 29% (7.70+/-0.29 vs
      5.43+/-0.29, P<0.01) respectively. CONCLUSION: FAM172A protein promotes cell
      proliferation, inhibits cell apoptosis and facilitates S-phases entry. It
      indicates that FAM172A protein is involved in cell growth regulation. Our
      findings provide a clue for further study on its physiological functions and
      roles in diabetic macroangiopathy.

PMID- 21092516
TI  - [Construction and identification of gene vector expressing PTEN while
      simultaneously silencing Livin].
AB  - OBJECTIVE: To study the effect of simultaneously increasing PTEN gene expression
      and inhibiting Livin gene expression on the gastric carcinoma cell line (BGC823)
      and construct a recombinant vector expressing PTEN while simultaneously silencing
      Livin. METHODS: The siRNA expression unit against Livin gene (siLivin) was
      cleaved from pRNAT-U6.1-Livin vector and then inserted into pCL-neo-PTE to
      construct the recombinant vector pCL-neo-PTEN-siLivin. Then pCL-neo-PTEN
      siLivinp, pCL-neo-PTEN, pRNAT-U6.1-Livin, pCL-neo and pRNAT-U6.1 were
      respectively transfected into the gastric carcinoma cell line (BGC823) with
      LipofectAMINE(TM) 2000. The mRNA and protein expression level of PTEN and Livin
      genes in each cell group was detected by fluorescent quantitative RT-PCR and
      Western blot. RESULTS: Recombinant vectors of pCL-neo-PTEN, pRNAT-U6.1-Livin and
      pCL-neo-PTEN-siLivin were constructed successfully. After transfection with pCL
      neo-PTEN-siLivin, the mRNA and protein expression level of PTEN (0.897+/-0.112)
      rose in BGC823 cells while Livin gene became silenced. And the characterization
      of regulated cell bioactivity improved. There were significant differences
      between transfected and control groups (P<0.05). And the inhibiting effect on the
      proliferation and metastasis of BGC823 cell by increasing PTEN expression and
      silencing Livin simultaneously was better than that only by regulating PTEN genes
      or Livin genes alternatively. CONCLUSION: The recombinant vector of expressing
      PTEN and silencing Livin gene simultaneously is successfully constructed.

PMID- 21092517
TI  - [A modified rat model for infection-induced stone formation].
AB  - OBJECTIVE: To employ a newly modified rat model for infection-induced bladder
      stone formation. METHODS: 24 adult male Sprague Dawley rats were divided into 3
      groups, model group (n=12), sham operation group (n=8) and control group (n=4).
      The surgical procedures were performed aseptically under anesthesia (25% Ultane
      1.0 g/kg). The bladder in model group was exposed through a short lower midline
      abdominal incision, the puncture needle (G18) with guideline was inserted
      aseptically into bladder, a metal wire, which have been contaminated by the
      Proteus mirabilis, was put into the puncture canal, then implanted into the
      bladder lumen through the guideline. In the sham operated group the puncture
      needle (G18) with guideline was inserted into bladder without metal wire
      implanted into the bladder. There was no any operation in control group. The rats
      were sacrificed by excessive anesthesia at 21 days post challenge. The bladder
      were removed aseptically and inspected for evidence of urolithiasis. RESULTS: On
      Day 2 after surgery, two rats died in model group, no rats died in other groups.
      Twenty-one days after surgery, all of rats in model group developed various-sized
      bladder stones. There was no stone formation in sham operation group and control
      group. All stones were verified by infrared spectroscopy and optical
      crystallography. These stone were struvite stone. CONCLUSION: This model has a
      less trauma, faster recovery and excellent stone formation so that it may be used
      for the study of infection stone.

PMID- 21092518
TI  - [The Global Pediatric Education Consortium: transforming pediatric training and
      child health through collaboration].

PMID- 21092519
TI  - [Considerations and suggestions for diagnosis and treatment of neonatal
      jaundice].

PMID- 21092520
TI  - [Roles of UGT 1A1 gene mutation in the development of neonatal hyperbilirubinemia
      in Guangxi].
AB  - OBJECTIVE: Neonatal unconjugated hyperbilirubinemia is one of the most common
      conditions encountered by the practicing pediatricians. Although it is usually
      self-limited and benign, the condition is of importance because of the rare
      instances in which severe hyperbilirubinemia can lead to bilirubin encephalopathy
      or kernicterus. The uridine diphosphate-glucuronosyl transferase 1A1 (UGT 1A1)
      gene controls bilirubin conjugation by determining the structure of the enzyme
      glucuronosyltransferase, which is synthesized in the hepatocyte. In the recent
      years much has been learned about the relationship between UGT 1A1 gene mutation
      and neonatal hyperbilirubinemia. This study aimed to investigate the roles of UGT
      1A1 gene mutation in the development of neonatal hyperbilirubinemia in Guangxi.
      METHODS: A total of 73 cases with hyperbilirubinemia and 31 healthy neonates were
      enrolled. UGT 1A1 G71R genotypes were identified by the (amplification refractory
      mutation system, ARMS) and direct sequencing method in all the neonates. To
      analyze the incidence of bilirubin encephalopathy, the peak (total serum
      bilirubin, TSB) concentration after 72 hours of age, and the possibility of TSB >
      20 mg/dl of each group. RESULTS: (1) The frequencies of allele G71R were 0.1915
      in this study, 0.2329 in hyperbilirubinemia group vs. 0.097 in healthy groups.
      The allele gene frequency of G71R in neonatal hyperbilirubinemia was higher than
      that in the normal group (P < 0.05). (2) Homozygous neonates had higher
      possibility to develop bilirubin encephalopathy and higher TSB concentration 72
      hours after birth (28.57%, 23.12 +/- 4.58) than the normal group (0%, 17.68 +/-
      2.69). The difference between the former two was significant (P < 0.001). (3) The
      TSB of the 5 neonates was > 20 mg/dl in G71R homozygous type, the odds ratio and
      95%CI were 7.955 (1.349, 46.899). CONCLUSION: (1) G71R mutation gene was
      associated with neonatal jaundice in Guangxi region. (2) The possibility of TSB >
      20 mg/dl in G71R homozygous was higher than those of the wild-type. (3) The
      incidence of bilirubin encephalopathy and TSB concentration after 72 hours of age
      for neonates who were homozygous to G71R gene were higher than the wild-type.

PMID- 21092521
TI  - [OATP 1B1 T521C/A388G is an important polymorphism gene related to neonatal
      hyperbilirubinemia].
AB  - OBJECTIVE: Multiple genetic and environmental factors contribute to the onset of
      many human diseases, such as neonatal hyperbilirubinemia. OATP 1B1 is an
      important polymorphism gene which transmembrane transports unconjugated
      bilirubin(UCB). Genetic polymorphisms that affect the functionality of the
      protein may potentially lead to altered transport characteristics. The
      T521C/A388G polymorphism of this gene has been reported to considerably reduce
      the transporting property of drugs like pravastatin, and may be involved in the
      membrane translocation of bilirubin. Some studies have shown that OATP 1B1
      mediates bilirubin uptake from blood into the liver, and the OATP 1B1
      polymorphism is a likely mechanism explaining the differences of bilirubin level
      in peripheral blood. The aim of this study was to evaluate the relationship
      between OATP 1B1 polymorphisms and neonatal hyperbilirubinemia. METHODS: A total
      of 220 newborn infants with hyperbilirubinemia were recruited from Hunan Children
      Hospital from November 2008 to December 2009 according to the diagnostic
      criteria. Age and sex matched control subjects comprised of 200 unrelated,
      hyperbilirubinemia-free newborns. Biochemical and clinical data were collected
      from the case history. One ml venous blood samples in EDTA vials were taken from
      each subject and DNA was isolated from peripheral leukocytes by standard methods,
      preserved in 4 degrees C. 1 - 2 ml venous blood samples were also taken for
      detecting the serum total bilirubin and direct bilirubin level by chemical
      oxidation method. OATP 1B1 T521C/A388G polymorphisms were determined using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. Allele and genotype frequencies were compared between patients and
      control. The gene polymorphism and risk of disease were also analyzed. Serum
      total bilirubin, conjugated bilirubin and unconjugated bilirubin levels were
      compared between different OATP 1B1 T521C/A388G genotypes. RESULTS: Allele
      frequencies in patients and control population were in Hardy-Weinberg equilibrium
      (P > 0.05). Allele and genotype frequencies of the OATP 1B1 T521C polymorphism in
      patients were significantly different from the controls. The OATP 1B1 521C allele
      frequency was only 8.2% in patients, while reached 14.0% in the control group
      which was very close to the frequency of common Chinese people. However, the
      proportion of wild type genotypes was significantly higher than those of the
      controls, reached 84.1%. The 521 C allele and genotypes carrying 521 C allele
      illustrated low risk for neonatal hyperbilirubinemia (OR = 0.530, 95%CI = 0.328 -
      0.857; OR = 0.541, 95%CI = 0.344 - 0.851). However, the frequencies of alleles
      and genotypes of SLCO1B1 A388G did not differ significantly from those of the
      controls, and this polymorphism did not influence susceptibility to such disease.
      Among the three OATP 1B1 A388G genotypes, the level of total serum bilirubin
      (TSB), direct bilirubin (DB) and unconjugated bilirubin (UCB) were significantly
      different. Values of TSB, DB and UCB were the highest in wild type subjects,
      lower in heterozygotes, and the lowest in mutant homozygotes. TSB and UCB in
      patients with wild type genotypes reached 602.5 umol/L and 585.0 umol/L
      respectively, nearly twice the average value of homozygous patients. While the
      TSB and UCB in homozygotes were below the average value of all patients, only
      351.7 umol/L and 338.8 umol/L respectively. CONCLUSIONS: Our findings indicated
      that OATP 1B1 A388G polymorphism has a notable influence on the serum bilirubin
      level in neonatal hyperbilirubinemia patients. The OATP 1B1 521T allele may be a
      potential risk factor of such disease. OATP 1B1 T521C/A388G was an important
      polymorphism gene which related with neonatal hyperbilirubinemia. Future study
      should involve other polymorphisms of OATP 1B1, more candidate genes and
      environmental risk factors. It is also necessary to investigate their association
      with the severity and prognosis of this disease in order to elucidate the genetic
      pathogenesis of neonatal hyperbilirubinemia as a complex disease. This study
      should be repeated in a larger population and different ethnic groups.

PMID- 21092522
TI  - [Meta analysis of the effect of immunoglobulin infusion on neonatal isoimmune
      hemolytic disease caused by blood group incompatibility].
AB  - OBJECTIVE: Neonatal isoimmune hemolytic disease is still one of the major causes
      of neonatal hyperbilirubinemia. The infants with severe hemolysis even need
      phototherapy and exchange transfusion. Early intravenous immunoglobulin infusion
      may block hemolysis to some extent. This study aimed to investigate the efficacy
      and safety of immunoglobulin infusion on neonatal isoimmune hemolytic disease by
      meta analysis. METHOD: All randomized controlled trials on the effect of
      immunoglobulin infusion on neonatal Rh and ABO incompatible hemolytic disease
      obtained by searching MEDLINE, Cochrane Library, EMBASE, CNKI and CBM were
      included. Meta analysis was done by Review Manager 4.2 software. RESULTS: Six
      trials with totally 456 neonates were included. There were 109 infants with Rh
      blood group incompatible hemolysis in 4 studies and 347 infants with ABO blood
      group incompatible hemolysis in 4 studies. There was no significant difference in
      gestational age, weight and sex between the immunoglobulin infusion and control
      groups. Compared with those neonates treated with only phototherapy, the infants
      treated with immunoglobulin and phototherapy had shorter duration of phototherapy
      (weighted mean difference, WMD -15.42, 95%CI -29.00 to -1.85), less chance to be
      given exchange transfusion (RR 0.25, 95%CI 0.17 to 0.39) and shorter duration of
      hospitalization (WMD -25.44, 95%CI -36.93 to -13.94). While intravenous
      immunoglobulin could not decrease the maximum serum bilirubin level (WMD -29.91,
      95%CI -78.24 to 18.42). There was no significant difference in the incidence of
      late anemia between the two groups. No adverse reaction was found in neonates who
      received immunoglobulin. CONCLUSIONS: The results of this meta analysis support
      that the intravenous immunoglobulin had some therapeutic effect on neonatal
      isoimmune hemolytic disease. The infants who received immunoglobulin had shorter
      duration of phototherapy and less chance to be given exchange transfusion. Well
      designed, double blind and randomized controlled trials with large sample size
      and long-term follow-up are needed for further evaluation of the efficacy and
      safety of the immunoglobulin therapy.

PMID- 21092523
TI  - [Dynamic evaluation on body weight gain in premature infants and its
      significance].
AB  - OBJECTIVES: To investigate the incidence of intra- and extrauterine growth
      retardation (EUGR) and growth restriction in premature infants, and to illustrate
      the growth pattern of them in postnatal and infantile period. METHODS: All
      premature infants were admitted to our neonatal intensive care unit (NICU) during
      the recent 7 years. The criteria for enrollment were (1) gestational age < 37
      weeks; (2) single fetus; (3) admitted within the first 24 hours of life; (4)
      hospitalization period >= 14 days; (5) clinical follow-up persisted till >= 3
      months of corrected gestational age. Intrauterine growth restriction (IUGR), EUGR
      and growth restriction were defined as having a measured growth value (weight)
      that was <= 10(th) percentile of Chinese infants' growth curve in corrected age
      on admission, discharge and follow-up period. Results were analyzed by using SPSS
      12.0 statistical software package by chi-square test, rank-sum test, and t test.
      RESULTS: Two hundred and thirty nine infants were involved, 134 were boys and 105
      girls. The incidence of IUGR and EUGR assessed by weight was 25.5% and 40.6%,
      respectively. The lower the birth weight was, the higher the incidence of IUGR
      and EUGR was. The percentile of body weight in the growth curve at discharge was
      lower than that at birth (Z = -7.784, P = 0.000). The incidence of growth
      restriction assessed by weight was 20.5%, 15.0%, 8.8%, 17.0%, 10.4%, 10.1%,
      11.9%, 7.0% at corrected gestational age of 38 - 40 weeks, corrected age of 28 d,
      61 d, 91 d, 122 d, 152 d, 183 d, and 274 d, respectively. The incidences of
      growth restriction were stable when the corrected age was older than 91 days. The
      incidence of growth restriction in female premature infants at 183 days'
      corrected age was higher than that in male children (chi(2) = 6.181, P = 0.017),
      the incidence was 19.3% and 3.8% respectively. During the follow-up period, most
      of the average body weight of premature infants whose gestational age was < 32
      weeks or birth weight <= 1500 g were lower than the 50(th) percentile of the
      growth curve except the average body weight of boys whose gestational age < 32
      weeks at corrected age of 2 and 4 months. CONCLUSIONS: Premature and/or low birth
      weight infants are at high risk of growth restriction, especially very low birth
      weight infants. The incidence of growth restriction decreased with growth. Long
      term prognosis requires further investigation.

PMID- 21092525
TI  - [Multicenter clinical study on umbilical cord arterial blood gas parameters for
      diagnosis of neonatal asphyxia].
AB  - OBJECTIVE: To obtain the normal range of statistics of umbilical artery blood gas
      parameters of the newborns for diagnosis of neonatal asphyxia. METHODS: From
      March 2008 through September 2009, 17 978 singleton term appropriate for
      gestational age (AGA) or larger than gestational age (LGA) newborns in six
      hospitals of five provinces/autonomous regions were consecutively enrolled in
      this prospective study. The normal ranges of umbilical artery blood gas
      parameters were obtained from 17 645 newborns with 1 min Apgar score >= 8. The
      correlations between umbilical artery blood pH, BE and prenatal high-risk
      factors, Apgar scores, and organ damage were analyzed. The diagnostic criteria
      for asphyxia included the following: (1) Having high-risk factors that might
      cause asphyxia; (2) 1 min Apgar score <= 7 (the respiratory depression must be
      present); (3) At least one organ showed evidence of hypoxic damage; (4) Other
      causes of low Apgar score were excluded. The study focused on the distributive
      characteristics of umbilical artery blood pH (clinically corrected by Eisenberg
      formula) and BE values of the asphyxiated and non-asphyxiated cases in low Apgar
      score group, as well as the sensitivity and specificity of different selected pH
      and BE threshold spots within their distributing ranges. RESULTS: Among the 17
      978 singleton term AGA or LGA newborns, the statistically normal range of
      umbilical artery blood pH, BE for the 17 645 cases with 1 min Apgar scores >= 8
      were 7.20 +/- 0.20 (x(-) +/- 1.96 s) and -7.64 +/- 10.02 (x(-) +/- 1.96 s),
      respectively. The pH well correlated positively with BE (r = 0.734, P < 0.01).
      The umbilical artery blood pH and BE values correlated positively with the Apgar
      scores. The umbilical artery blood pH and BE values correlated negatively with
      organ damage (r = 1, the P values = 0.000 for both). Among the 333 low Apgar
      score cases, the umbilical artery blood pH corrected values and BE values of the
      asphyxiated group (163 cases) were 7.011 +/- 0.09 (x(-) +/- s) and -14.98 +/-
      2.99 (x(-) +/- s), being lower than 7.18 +/- 0.07 (x(-) +/- s) and -8.56 +/- 4.68
      (x(-) +/- s) of the non-asphyxiated group (170 cases) respectively (t = 14.3,
      8.79, P values < 0.001). The distributing ranges of the umbilical artery blood pH
      corrected values and BE values of the asphyxiated group were < 7.00- < 7.20 and <
      -10- < -18, respectively. Within the above ranges, none of selected spots with
      both high sensitivity and high specificity was found. CONCLUSIONS: The
      statistically normal range of the umbilical artery blood pH and BE for the
      newborns was 7.20 +/- 0.20 (x(-) +/- 1.96 s) and -7.64 +/- 10.02 (x(-) +/- 1.96
      s) respectively. Owing to individual differences and the measured blood pH should
      be clinically corrected, the statistical threshold was not fully equal to the
      clinicopathological threshold. The pathological threshold of pH or BE for
      neonatal asphyxia is a range rather than a fixed point. The distributing range of
      the umbilical artery blood pH clinically corrected values and BE values for
      neonatal asphyxia were < 7.00- < 7.20 and < -8- < -18, respectively. In the
      presence of the other four indexes for diagnosing neonatal asphyxia, the blood
      gas index should be used flexibly in the above ranges.

PMID- 21092526
TI  - [Alveolar capillary dysplasia: a case report and review of literature].
AB  - OBJECTIVE: To report a newborn infant who died of alveolar capillary dysplasia
      (ACD). The literature on about 20 cases of ACD was reviewed. METHODS: A
      retrospective review of records of infants from Medline with a diagnosis of ACD
      was carried out. RESULTS: The case was a newborn female infant who developed
      respiratory distress 5 hours after an uncomplicated delivery. She died at the
      fourth day after birth despite full ventilatory support. The lung autopsy
      provided a diagnosis of ACD. In the 21 infants, 7 were male and 14 were female;
      19 infants were born full-term and 2 were born pre-term. The birth weight of 19
      infants and Apgar score of 15 infants were normal; 16 infants developed
      progressing tachypnea and cyanosis within 24 hours of age, 5 developed cyanosis
      at 1 day to 19 days. Echocardiography demonstrated a right to left shunt in the
      hearts of all the 21 infants, and pulmonary hypertension in 20 infants. Twenty
      infants were treated with conventional mechanical ventilation, 7 infants with
      high-frequency oscillatory ventilation and 12 infants with extracorporeal
      membrane oxygenation (ECMO). Fourteen infants were also treated with inhaled
      nitric oxide therapy and 4 with exogenous surfactant. Diagnostic open lung biopsy
      was performed in 6 infants. The chest radiography showed normal findings in 3
      infants, pneumothoraces in 9 infants, reticular markings, granular, patchy or
      diffuse opacity in lungs of 7 infants, and decreased pulmonary vascular markings
      in two infants. All the 21 infants died; 8 of them died within 10 days of age, 7
      within 30 days of age, and one died at the age of 4 months who was the longest
      survivor. Fourteen infants were associated with congenital malformations, such as
      cardiovascular, gastrointestinal, and genitourinary systems, including one infant
      associated with chromosomal abnormalities, two infants of familial genetic
      predisposition. CONCLUSIONS: At present, ACD is still a disease with poor
      prognosis, significant medical expenses and no specific treatment. When
      respiratory failure or persistent pulmonary hypertension (PPHN) is persistent
      after routine treatment in an infant, ACD should be highly suspected and
      conventional open-lung biopsy should be preformed to confirm the diagnosis.

PMID- 21092527
TI  - [A case report of acquired syphilis in an infant caused by feeding after chewing
      the food].

PMID- 21092528
TI  - [Maple syrup urine disease of neonates: report of two cases and review of
      literature].
AB  - OBJECTIVE: To analyze and summarize clinical manifestation of maple syrup urine
      disease (MSUD) of neonates. METHODS: Data of two cases with neonatal MSUD and the
      reports of 15 cases seen in the past 15 years in China were reviewed and
      analyzed. RESULTS: There was an increasing number of reports of cases with
      neonatal MSUD. All the 17 cases had the symptom of poor feeding between 3 h and 8
      d after birth; 7 cases had family history; 14 cases showed progressive neurologic
      signs. Odor of maple syrup occurred in 8 cases. Blood levels of branched-chain
      amino acids (BCAA) significantly increased in 13 cases and 6 neonates were
      diagnosed using tandem mass spectrometry. Urinary levels of BCAA and metabolite
      elevated in 12 cases and 5 neonates were diagnosed using gas chromatography-mass
      spectrometry. MRI/CT demonstrated abnormal signal in 10 cases. Twelve cases died
      or their parents gave up treatment and one case had cerebral palsy; 4 cases were
      treated with BCAA-free formula milk and showed improved outcome. CONCLUSION:
      Newborns with MSUD often had early appeared non-specific symptoms with poor
      feeding and lethargy, most cases later showed an odor resembling maple syrup and
      neurologic signs. For patients who were suspected of having MSUD, blood and urine
      concentrations of BCAA should be tested for early diagnosis. Specific MRI edema
      signal from brain suggests the possibility of MSUD. Early intervention and
      treatment after diagnosis, with compliance of parents, would improve the
      patient's outcome.

PMID- 21092529
TI  - [Experts consensus on principles for diagnosis and treatment of neonatal
      jaundice].

PMID- 21092530
TI  - [Evidence-based guidelines for diagnosis and treatment of common renal diseases
      in children (for trial) (VI): guidelines for the diagnosis and treatment of lupus
      nephritis].

PMID- 21092531
TI  - [Interpretation of the experts consensus on principles for diagnosis and
      treatment of neonatal jaundice].

PMID- 21092532
TI  - [Intensive reading of lupus nephritis: evidence-based guidelines on diagnosis and
      treatment of common renal diseases in children (VI)].

PMID- 21092533
TI  - [Clinical characteristics of 34 children with Hodgkin lymphoma and efficacy of
      treatment with chemotherapy plus low dose radiotherapy on involved sites].
AB  - OBJECTIVE: To summarize the clinical features and to evaluate outcomes and to
      assess therapeutic effects in 34 children and adolescents with Hodgkin lymphoma
      treated with risk-adapted combination chemotherapy and low-dose, involved-field
      radiation therapy (IFRT) in China. METHOD: From January 2003 to April 2009, 34
      hospitalized children with Hodgkin lymphoma were enrolled into the BCH-HL 2003
      protocol (revised CCG 5942) in our hospital. Pathological samples were reviewed
      centrally and classified based on the World Health Organization guidelines.
      Staging was based on clinical evaluation and was defined by the Ann Arbor staging
      system. The 34 patients were treated according to the different risk factors in
      three treatment groups (standard, intermediate, and high risk), and received risk
      adapted combination chemotherapy and IFRT. All analyses were calculated by the
      statistical program SPSS. RESULT: Of the 34 Hodgkin lymphoma patients, 28 were
      male and 6 were female. The median age was 8.7 years (range from 4 years to 15
      years) at the time of diagnosis. In terms of clinical presentation, 53% had bulky
      lymph nodes, 47.1% had more than 4 node regions involved and 44% had "B" symptoms
      at presentation. The distribution for stage of disease was 0% for Stage I, 21%
      for Stage II, 35% for Stage III and 44% for Stage IV disease. All patients had
      classical histology consisting of three different sub-discipline: 22 cases of
      mixed cellularity (64.7%). In pathological samples of 25 cases there was EBV
      encoded RNA (EBER) or latent membrane protein (LMP) staining. The overall
      survival (OS) was 100% and the 5-year event-free survival was 94.1% with a median
      follow-up of (26.1 +/- 16.3) months. Two patients had early relapse after
      treatment was finished. Organ toxicity was limited to hematological grades III
      and IV at rates of 40% and 71% respectively. CONCLUSION: Childhood Hodgkin
      lymphoma in our study was more frequently seen in male school aged children.
      Combined-modality therapy using risk-adapted chemotherapy with radiation is
      effective and well tolerated. The overall prognosis was good.

PMID- 21092534
TI  - [The value of the New York University Pediatric Heart Failure Index in chronic
      heart failure in children].
AB  - OBJECTIVE: The study was designed to explore the value of the New York University
      Pediatric Heart Failure Index (NYU PHFI) for diagnosing and grading chronic heart
      failure in children. METHODS: Totally 105 children with chronic heart failure or
      structural heart disease but without signs and symptoms of heart failure were
      enrolled. They were diagnosed using modified Ross score, NYU PHFI and NT-proBNP,
      respectively. According to modified Ross score as the referent criteria, the
      diagnostic value of NYU PHFI in quantifying chronic heart failure severity in
      children was studied. Furthermore, according to the grading of heart failure
      using modified Ross score, the area under the ROC curves of NYU PHFI was
      examined, respectively, in order to find out the optimal cut-off point. RESULTS:
      NYU PHFI score was positively correlated with the modified Ross score (r = 0.909,
      P = 0.000). According to modified Ross score, NYU PHFI scores in different
      severity of heart failure in children differed significantly (F = 80.034, P =
      0.000). A significantly positive correlation was found between plasma NT-proBNP
      and modified Ross score, and between NT-proBNP and NYU PHFI score. Correlation
      coefficients between plasma NT-proBNP and modified Ross score, and between plasma
      NT-proBNP and NYU PHFI score were 0.752 and 0.918, respectively. The correlation
      between NYU PHFI and plasma NT-proBNP was superior to that between modified Ross
      score and plasma NT-proBNP. According to modified Ross scores of 0 - 2 as being
      without heart failure, 3 - 6 as mild degree of heart failure, 7 - 9 as moderate
      degree of heart failure and 10 - 12 as severe degree of heart failure, the areas
      under the ROC curve of the NYU PHFI diagnosing if heart failure was present,
      differentiating moderate from mild and severe from moderate heart failure were
      0.982, 0.942 and 0.918, respectively, and the sum of sensitivity and specificity
      was favorite when 6, 10 and 13 scores were set as cut-off value diagnosing the
      presence of heart failure, differentiating moderate from mild, and severe from
      moderate heart failure, respectively. According to above classification of heart
      failure based on NYU PHFI score, plasma NT-proBNP concentration was significantly
      different in different degree of heart failure (F = 53.31, P < 0.001). Plasma NT
      proBNP concentration in those without heart failure was significantly lower than
      that of mild heart failure, and it was also significantly lower in mild heart
      failure than that of severe heart failure. CONCLUSION: NYU PHFI was highly
      valuable for diagnosing chronic heart failure in children and 0 - 6 scores as
      being without heart failure, 7 - 10 scores as mild degree, 11 - 13 scores as
      moderate degree and 14 - 30 scores as severe degree of heart failure could be
      used as the reference criteria of different severities of heart failure.

PMID- 21092535
TI  - [Clinical characteristics of hepatic veno-occlusive disease in 6 children with
      hematologic neoplasm treated with 6-thioguanine].
AB  - OBJECTIVE: To improve the treatment of drug related childhood hepatic veno
      occlusive disease (HVOD), clinical characteristics of 6 children with hematologic
      neoplasm from 2 hospitals of China Children's Leukemia Group (CCLG) treated with
      6-thioguanine (6-TG) complicated with HVOD were analyzed. METHOD: All the drug
      related HVOD patients were treated with CCLG acute lymphoblastic leukemia (ALL)
      2008 protocol. They were from Children's Hospital of Fudan University and
      Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical
      Sciences & Peking Union Medical College from April 2008 to April 2009. The
      diagnosis was made according to the modified Seattle criteria and Baltimore
      criteria, including 2 or 3 of the following clinical features: hepatomegaly and
      upper right abdominal pain, jaundice (bilirubin >= 35 umol/L), ascites or
      confirmed by pathology. The 6 HVOD patients' clinical manifestations, laboratory
      finding, imageologic and pathologic data were collected and analyzed. RESULT: Of
      the 6 patients, 2 were males and 4 females. Mean age of the 6 patients was 3.89
      years (range from 3 years 1 month to 4 years 11 months). The original disease was
      acute lymphoblastic leukemia. HVOD occurred during chemotherapy protocols of CAM
      (CTX + Ara-C + 6-TG) or maintenance period (MTX + 6-TG). Most of 6 HVOD patients
      presented with pain in liver area, hepatomegaly on imaging, elevated
      aminotransferase and bilirubin (often >= 35 umol/L), hydroperitonia was common,
      one with pleural fluid, illegible hepatic veins. All the patients recovered after
      being treated with hepatoprotective, jaundice-relieving and supportive
      therapeutics, some patients were treated with low molecular weight heparin. The
      prognoses were good. CONCLUSION: HVOD was a serious complication of chemotherapy
      with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight
      heparin could improve the prognosis.

PMID- 21092536
TI  - [Introduction to 2010 version of recommendations for enteral nutritional support
      to premature infants and nutritional demands of premature infants].

PMID- 21092537
TI  - [Aortic atresia with ventricular septal defect in a case].

PMID- 21092538
TI  - [Transcatheter closure of aorto-pulmonary septal defect in an infant: a case
      report].

PMID- 21092539
TI  - [A case of child myiasis].

PMID- 21092540
TI  - [Overview and new prospects of fetal medicine].

PMID- 21092541
TI  - [Summary of the international workshop on developmental origins of health and
      disease in China].

PMID- 21092542
TI  - [Factors relevant to newborn birth weight in pregnancy complicated with abnormal
      glucose metabolism].
AB  - OBJECTIVE: To investigate the influencing factors of neonatal birth body mass in
      women with abnormal glucose metabolism during pregnancy. METHODS: A study was
      conducted on 1157 singleton gravidas, who were diagnosed and treated for abnormal
      glucose metabolism and delivered in the Department of Obstetrics and Gynecology,
      First Hospital, Peking University from January 2005 to December 2009, by
      reviewing the medical records. Based on the pre-pregnant body mass index, the
      selected cases were divided into 4 groups: low body mass group [body mass index
      (BMI) < 18.5 kg/m(2), n = 53], ideal body mass group (BMI 18.5-23.9 kg/m(2), n =
      647), over body mass group (BMI 24.0-27.9 kg/m(2), n = 323), and obese group (BMI
      >= 28.0 kg/m(2), n = 134). 1157 newborns were divided by birth body mass into 3
      groups: normal birth body mass group (body mass 2500-4000 g, n = 987), of which
      545 cases of birth body mass 3000-3500 g for the appropriate newborns, macrosomia
      group (body mass >= 4000 g, n = 112); low birth body mass group (body mass < 2500
      g, n = 58). The following information was collected, including pre-pregnancy body
      mass, height, gestational age of diagnosis and body mass gain after diagnosis,
      maternal serum level of cholesterol, history of adverse pregnancy, and family
      history of diabetes, gestational age, delivering body mass, neonatal birth body
      mass. The influence of pre-pregnant BMI, body mass gain during pregnancy,
      gestational age of diagnosis, body mass gain after diagnosis, maternal serum
      level of cholesterol, family history of diabetes on the newborns' birth body mass
      was analyzed. The appropriate ranges of gestational body mass gain were
      calculated in women with abnormal glucose metabolism. RESULTS: (1) The average
      neonatal birth body mass for each group respectively were (3142 +/- 333) g for
      low body mass group, (3339 +/- 476) g for the ideal body mass group, (3381 +/-
      581) g for over body mass group, and (3368 +/- 644) g for obese group. The
      neonatal birth body mass was increasing with maternal pre-pregnant BMI, and
      average birth body mass of the newborns in low body mass group was lower than
      other 3 groups, respectively, the difference was statistically significant (P <
      0.05). The difference was not statistically significant (P > 0.05), when it was
      compared among the obese group, ideal weight group and over body mass group. (2)
      The body mass gain during pregnancy in women delivered normal birth weight
      newborn and delivered macrosomia for each group respectively were (13.5 +/- 4.5)
      and (17.1 +/- 5.4) kg for the ideal body mass group, (11.6 +/- 4.9) and (15.3 +/-
      6.4) kg for the over body mass group, (10.3 +/- 5.0) and (14.7 +/- 7.4) kg for
      the obese group. The difference was statistically significant in 3 groups (P <
      0.05). The difference of body mass gain during pregnancy in women delivered
      normal birth weight newborn and delivered macrosomia for low body mass group
      could not be compared statistically, because of only 1 case delivered macrosomia.
      (3) The gestational age of diagnosis in women who delivered normal birth weight
      newborn and macrosomia for the ideal body mass group respectively were (27.8 +/-
      5.8) and (29.8 +/- 5.3) weeks, the difference was statistically significant (P <
      0.05). The gestational age of diagnosis in gravidas who delivered normal birth
      weight newborn and macrosomia for the over body mass group respectively were
      (26.7 +/- 6.8) and (30.2 +/- 4.1) weeks, the difference was statistically
      significant (P < 0.05). The gestational age of diagnosis in women who delivered
      normal birth weight newborn for obese group was (26.2 +/- 7.5) weeks, less than
      that of pregnant women who delivered macrosomia [(25.7 +/- 9.3) weeks], but the
      difference was not statistically significant (P > 0.05). The difference of the
      diagnosed gestational age for low body mass group could not be compared
      statistically, because of only 1 case delivered macrosomia. (4) The serum
      triglyceride (TG) levels of pregnant women who delivered macrosomia was (3.1 +/-
      1.5) mmol/L, higher than that of pregnant women who delivered normal birth weight
      newborn [(2.7 +/- 1.2) mmol/L], and the difference was statistically significant
      (P < 0.01). The serum high density lipoprotein cholesterol (HDL-C) levels of
      pregnant women who delivered macrosomia was (1.4 +/- 0.3) mmol/L, lower than that
      of pregnant women who delivered normal birth weight newborn [(1.7 +/- 0.9)
      mmol/L], and the difference was statistically significant (P < 0.01). The serum
      low-density lipoprotein cholesterol (LDL-C) and cholesterol level of pregnant
      women who delivered macrosomia respectively was (2.8 +/- 0.8) and (5.4 +/- 1.1)
      mmol/L, less than those of pregnant women who delivered normal birth weight
      newborn [(3.0 +/- 0.9) mmol/L and (5.6 +/- 1.1) mmol/L], but the difference was
      not statistically significant (P > 0.05). (5) The final regression model of
      variables into the top three were pre-pregnant BMI, body mass gain during
      pregnancy and maternal serum level of HDL-C, when analyzing the related factors
      of affecting neonatal birth body mass with multiple logistic regression analysis
      such as age, history of adverse pregnancy, family history of diabetes, pre
      pregnancy BMI, body mass gain during pregnancy and after diagnosis of abnormal
      glucose metabolism, maternal serum level of cholesterol, abnormal glucose
      metabolism categories, gestational age and other factors (P < 0.01). CONCLUSION:
      Pre-pregnant BMI, body mass gain during pregnancy and maternal serum level of HDL
      C may affect the neonatal birth body mass whose mothers were complicated with
      abnormal glucose metabolism during pregnancy.

PMID- 21092543
TI  - [Intrapartum operation on fetuses with birth defects and its outcome].
AB  - OBJECTIVE: To discuss the value of intrapartum operation in management of birth
      defects and the prognosis. METHODS: From August 2008 to November 2009, 11 fetuses
      were identified with birth defects through 3D color Doppler ultrasound and
      confirmed by MRI and fetal karyotype in the Maternal Fetal Medicine Center,
      Affiliated Shengjing Hospital, China Medical University including three
      lymphangiomas, two congenital diaphragmatic hernias (CDH), one sacrococcygeal
      teratoma, three omphalocele and two gastroschisi. All the above identified birth
      defects were indications for surgery. All fetuses were born abdominally and
      received intrapartum operations, including three intrapartum fetal operations
      with placental infusion (two repairs of CDH, one sacrococcygeal teratoma
      resection), six ex-utero intrapartum treatment (EXIT; two repairs of omphalocele,
      two repairs of gastroschisi, two lymphangioma resection) and two surgeries in
      house (one omphalocele repair and one lymphangioma resection). Both the mothers
      and fetuses were regularly followed up. RESULTS: (1) OPERATIONS: the average
      operating time for the three intrapartum fetal operations was 89 minutes, 5.5
      minutes for the six EXIT, during which EXIT was performed first, followed by
      blocking the umbilical circulation and neonatal surgery, and 37 minutes for the
      two surgeries in house. All neonates survived except for one death from severe
      CDH at 3.5 hours after the operation. The average blood loss for cesarean section
      and fetal operation was 275 ml. All mothers recovered soon without fever or
      infection and were discharged three to five days after the operation. (2) Follow
      ups: the ten survived neonates were followed up at 1-18 months at the pediatric
      clinics and all were growing and developing normally except for one baby with
      gastroschisi suffered from enteral torsion and feeding intolerance showed lower
      weight than babies at the same age, but caught up to normal at four months old
      after posture therapy. One baby with mild CDH developed pulmonary infection at
      two months after operation with 1/4 pneumothorax on chest X-ray, and were
      hospitalized for two weeks. At six months old, patent ductus arteriosus was
      diagnosed in the same baby and chest X-ray was normal. The baby with omphalocele
      was complicated with ventricular septal defect before operation and the cardiac
      function was normal during follow-ups for one year. The baby with sacrococcygeal
      teratoma was reported to have no automatic micturition, but recovered to normal
      at one month of age. CONCLUSION: Babies with certain birth defects can be managed
      through intrapartum operation with better outcomes.

PMID- 21092544
TI  - [Effects of severe hyperglycaemia in pregnancy and early overfeeding on islet
      development and insulin resistance].
AB  - OBJECTIVE: Study the effects of early overfeeding in the adult offspring of
      mother with severely hyperglycaemia in pregnancy to islet development and insulin
      resistance. METHODS: Thirty healthy female Wistar rats were mated with 10 male
      Wistar rats and the morning on which sperm were found in three different visual
      fields of the vaginal smear was designated pregnancy day 1. The pregnant rats
      were intraperitoneally administered with Streptozotocin (STZ, 50 mg/L) on 5th day
      of pregnancy, and blood glucose exceeded 20 mmol/L to induce severely gestational
      diabetes mellitus (SDM) model. The pregnant Wistar rats were assigned to two
      experimental groups: SDM (n = 16) and control (n = 8). Litter size reduction in
      the lactation period induced early postnatal overfeeding model. Offspring were
      divided into three groups according to the level of blood glucose in pregnancy
      and feeding patterns in lactation: (1) control group (CG): euglycemia in
      pregnancy, eight pups in lactation; (2) severely gestational diabetes mellitus
      normal feeding (SDM-N): severely gestational diabetes mellitus, eight pups in
      lactation; (3) severely gestational diabetes mellitus-overfeeding (SDM-O):
      severely gestational diabetes mellitus, four pups lactation. At the end of the
      lactation period, all pups were fed standard laboratory chow adlibitum until the
      date of the experiments. Offspring body weight was measured weekly after
      ablactation. Serum insulin was measured by enzyme-linked immunosorbent assay
      (ELISA) and pancreatic islet morphology was analyzed by immunohistochemistry
      (IHC) in all three groups at 26 weeks of age. RESULTS: (1) Blood glucose of
      pregnant Wistar rats: SDM (28.3 +/- 5.1) mmol/L was statistically higher than
      control (6.3 +/- 1.4) mmol/L (P < 0.05). (2) Growth rates of body weight in 3-7
      weeks and 3-9 weeks: SDM-N: (4.6 +/- 1.3)% and (6.8 +/- 2.5)%, SDM-O: (3.2 +/-
      0.7)% and (4.6 +/- 1.2)%, CG: (2.9 +/- 0.6)% and (4.1 +/- 0.8)%. The growth rates
      of body weight in SDM-N and SDM-O were both significantly higher than those in CG
      (P < 0.05). (3) Body weight at 26 weeks: CG: (486 +/- 132) g, SDM-N: (387 +/-
      115) g, SDM-O: (382 +/- 122) g. There was no statistical difference among the
      three groups (P > 0.05). (4) Fasting plasma glucose (FPG), fasting insulin
      (FINS), homeostasis model of insulin resistance (HOMA-IR) and insulin sensitivity
      index (ISI): at 26 weeks, the SDM-offspring has normal FPG, but more insulin was
      needed to keep it normal. The insulin level of SDM-O [(12.6 +/- 3.3) mU/L] was
      statistically higher than those of SDM-N [(10.9 +/- 3.3) mU/L] and CG [(8.6 +/-
      0.8) mU/L] (P < 0.05). The ISI of SDM-O (0.020 +/- 0.006) was significantly
      smaller than its HOMA-IR (2.40 +/- 0.62, P < 0.05). (5) The morphological change
      of pancreatic islet: The islets of CG and SDM-N were round or ellipse and have
      clear boundary between endocrine and exocrine parts and the beta cells
      distributed equally. However, SDM-O islets were not of uniform size and most of
      islets were hyperplasia and hypertrophy. (6) Relative beta cell area of pancreas,
      beta-cell area and islet size: SDM-O: (1.81 +/- 0.31)%, (57.1 +/- 3.2)% and
      (39,067 +/- 3308) um(2); SDM-N:(1.34 +/- 0.43)%, (60.9 +/- 0.6)% and (30,570 +/-
      4824) um(2); CG: (1.11 +/- 0.26)%, (63.7 +/- 2.7)% and (26,443 +/- 4431) um(2).
      SDM-O has significantly increasing beta-cell mass, hypertrophic islet size and
      slightly decreasing beta-cell percentage compared with other two groups (P <
      0.05). CONCLUSIONS: The exposure of severely hyperglycemia in pregnancy induces
      low weight infant and postnatal catch-up growth leading to the possibility of
      insulin resistance (IR) in adult and early postnatal overfeeding will accelerate
      such course. Islet morphology of SDM-N has no significant change, indicating that
      maternal diabetes mainly affected beta-cell function but not islet morphological
      features. SDM overfeeding results in early impairment of islet morphology and
      function, indicating that the compensation ability of islets has already been
      impaired and the risk of further development of impaired glucose tolerance (IGT)
      and diabetes. In conclusion, the nutritional environment in early life (duration
      of pregnancy and lactation) participate in the metabolic programming in
      adulthood.

PMID- 21092545
TI  - [Analysis of 96 cases with cesarean scar pregnancy].
AB  - OBJECTIVE: To investigate the clinical manifestation, diagnosis, therapies and
      medical economics of cesarean scar pregnancy (CSP). METHODS: From Jan. 2005 to
      Dec. 2008, 96 patients with CSP treated in Obstetrics and Gynecology Hospital of
      Fudan University were studied retrospectively. Those cases were divided into 3
      groups. Thirty-three patients were treated with methotrexate (MTX) 50 mg/m(2)
      intravenously guttae in group A. Among that 18 cases were treated with MTX, after
      5-10 days they underwent dilation and curettage of uterus; 15 cases were given by
      dilation and curettage first if the level of serum human chorionic gonadotrophin
      beta (beta-hCG) descent less than 30% in every 48 hours for 3 times after
      curettage, then MTX (50 mg/m(2)) intravenously guttae. Sixty patients were
      treated with MTX 100 mg bilateral uterine artery injection and embolization in
      group B. After 2 days, they underwent curettage. Group C: 3 patients were treated
      with laparotomy lesion excision. The following clinical parameters were compared,
      including blood loss (M), lesion diameter (x(-) +/- s), blood beta-hCG level (M)
      before treatment, the number of cases with myometrial thickness anterior to the
      CSP <= 3 mm, the resistant index (RI) <= 0.5, expense (x(-) +/- s), hospital days
      (x(-) +/- s) in those 3 groups. The correlation of blood loss with lesion
      diameter and blood beta-hCG level was studied. RESULTS: (1) Clinical
      manifestation: bleeding loss were 20 ml in MTX + curettage of group A, 10 ml in
      curettage + MTX of group A, 12 ml in group B and 200 ml in group C. The volume of
      bleeding loss in group C was significantly higher than those in group A or group
      B (P < 0.01). The lesion diameter were (23 +/- 15) mm in curettage + MTX of group
      A and (30 +/- 14) mm of group B, which were higher than (16 +/- 8) mm of MTX +
      curettage of group A (P < 0.01). The lesion diameter of (52 +/- 7) mm in group C
      were significantly bigger than those in the other groups (P < 0.01). The level of
      blood beta-hCG levels were 21 592 U/L in MTX + curettage of group A, 979 U/L in
      curettage + MTX of group A, which reach statistical difference (P < 0.05). The
      level of blood beta-hCG levels were 11 312 U/L in group B and 101 U/L in group C.
      Among 28 cases with RI <= 0.5, there was 8 cases in group A (24%, 8/33), 18 cases
      in group B (30%, 18/60) and 2 cases in group C (2/3). Among 23 cases with
      myometrial thickness anterior to the CSP <= 3 mm, there was 21 cases in group B
      (35%, 21/60), which were significantly higher than 2 in group A (6%, 2/33) and
      none in group C (P < 0.05). The expense were (5578 +/- 3679) yuan in MTX +
      curettage of group A and (5346 +/- 2765) yuan in curettage + MTX of group, which
      did not reach statistical difference (P > 0.05). The expense were (7860 +/- 2104)
      yuan in group B, which were significantly higher than those in group A and (5004
      +/- 421) yuan in group C (P < 0.05). The hospital days were (15 +/- 8) days and
      (19 +/- 14) days of group A, (16 +/- 10) days in group B and (17 +/- 8) days in
      group C, there was no significant difference among those treatments (P > 0.05).
      (2) Correlation: there was positive correlation between bleeding loss and lesion
      diameter (r = 0.31, P < 0.05) or blood beta-hCG level (r = 0.35, P < 0.05).
      CONCLUSIONS: MTX intravenously guttae, MTX uterine artery injection and
      embolization, and laparotomy lesion excision were all properly used in treatment
      of CSP. MTX uterine artery injection and embolization was recommended for those
      with big lesion, high beta-hCG level, less myometrial thickness anterior to the
      CSP or plentiful blood supply of the lesion but the expense might be high.

PMID- 21092546
TI  - [Prevalence of fecal incontinence among adult women in Beijing district].
AB  - OBJECTIVE: To investigate the prevalence of fecal incontinence (FI) among adult
      women in Beijing area, and to analysis risk factors associated with FI. METHODS:
      A stratified multiple-cluster systemic method was used to recruit women >= 20
      years old in 6 districts of Beijing. A self-administrated questionnaire was used
      to collect information about FI and possible risk factors. RESULTS: There were
      three thousand and 58 women participated in the survey, the average age was (48
      +/- 16) years (range 20-79 years). The prevalence of FI was 1.28% (39/3058),
      which was related to age. There were five factors entered the logistic regress
      model, which were included age >= 40 years old (OR = 3.3, 95%CI: 1.7-6.8),
      urinary incontinence (OR = 3.0, 95%CI: 1.5-6.1), vaginal delivery (OR = 2.4,
      95%CI: 1.2-4.9), household per capita income <= 2000 RMB per month (OR = 3.3,
      95%CI: 1.6-6.5), and feeling fatigue (OR = 3.0, 95%CI: 1.5-5.8). CONCLUSION:
      Prevalence of FI is low among adult women in Beijing area, while risk factors
      associated with FI are complicated and further studies are necessary to be
      conducted.

PMID- 21092547
TI  - [Factors associated with quality of life in survivors of gestational
      trophoblastic neoplasm after chemotherapy].
AB  - OBJECTIVE: To measure the quality of life (QoL) of gestational trophoblastic
      neoplasia (GTN) survivors after chemotherapy by using a self-invented scale, and
      to explore the factors associated with QoL. METHODS: The design of questionnaire
      was based on a series of internationally valid QoL scales, which was tested by
      epidemiology and showed good reliability and validity. A total of 100 survivors
      of GTN patients from Peking Union Medical College Hospital participated in this
      survey from December 2008 to May 2009. RESULTS: Patients with disease-free more
      than three months after chemotherapy enjoys a good QoL, while only 16% (16/100)
      of survivors feel general overall QoL, but no one feels bad QoL. As refer to
      sexual function, more than half of these patients (70%, 70/100) satisfied with
      their sexual life, while there were still 47% (47/100) and 45% (45/100) of the
      patients complaining of decreased sexual desire and dryness of vagina. 66%
      (66/100) of the GTN survivors expressed depression, and 50% (50/100) of patients
      complained anxiety, which were potential factors influencing QoL of GTN
      survivors. Relevant analysis explored the possible predictors of QoL for GTN
      patients, including physical function (r = 0.609, P < 0.01), sexual function (r =
      0.473, P < 0.01), and social psychology (r = 0.294, P < 0.01). CONCLUSIONS: GTN
      survivors have an overall good QoL after chemotherapy, the possible predictors of
      QoL for GTN patients include physical function, sexual function and social
      psychology. The sexual dysfunctions mostly present with short of sexual desire
      and dryness of vagina. Fear of recurrence may be a potential factor influencing
      QoL a long term after remission.

PMID- 21092548
TI  - [Influence of urodynamic factors on urinary retention in patients with cervical
      carcinoma after radical hysterectomy].
AB  - OBJECTIVE: To study the effect of urodynamic factors on the urinary retention of
      the patients with cervical cancer received radical hysterectomy. METHODS: Seventy
      two patients with cervical cancer International Federation of Gynecology and
      Obstetrics (FIGO) stage Ib1 to IIa hospitalized in Fujian Provincial Maternity
      and Child Health Hospital between June 2006 and August 2009, who were not found
      any abnormal representation of urodynamics before the operation, were divided
      into the group with urinary retention and the group without urinary retention
      based on whether urinary retention after the operation. All patients were
      detected by urodynamic examination following radical hysterectomy. Data obtained
      from urodynamic examination were analysed by logistic regression to evaluate the
      influence of urodynamic factors on the urinary retention postoperation. RESULTS:
      Twenty-one patients out of all were found with urinary retention after the
      operation, the incidence rate of urinary retention was 29%. The first sensation
      after operation in both groups were increased significantly than those before
      operation [(171 +/- 61) ml vs. (126 +/- 28) ml, (134 +/- 39) ml vs. (119 +/- 17)
      ml, all P < 0.05], while the maximum volume [(337 +/- 66) and (300 +/- 66) ml,
      respectively], the compliance [(31 +/- 25) and (29 +/- 18) ml/cm H2O (1 cm H2O =
      0.098 kPa), respectively], the maximum flow rate [(10 +/- 4) and (12 +/- 5) ml/s,
      respectively] and the pressure at the maximum flow rate [(27 +/- 9) and (32 +/-
      8) cm H2O, respectively] were decreased obviously after radical hysterectomy in
      both the group with urinary retention and the group without urinary retention
      (all P < 0.05), compared with the corresponding value before the operation. The
      urodynamic changes in urinary retention group was much more severe than those in
      group without urinary retention (P < 0.05). The single factor analysis results
      showed that bladder destusor dysfunction (OR = 8.20, 95%CI: 2.62-25.66, P < 0.01)
      and lack of sensation (OR = 6.90, 95%CI: 1.95-24.43, P < 0.01) were relevant to
      the urinary retention post-operation. While there were not relationship was found
      between low compliance bladder (OR = 1.99, 95%CI: 0.70-5.63, P = 0.195), detrusor
      overactivity (OR = 2.51, 95%CI: 0.73-8.67, P = 0.144), bladder outlet obstruction
      (OR = 3.77, 95%CI: 0.76-18.57, P = 0.104) or dyssynergia of urethral external
      sphincter (OR = 2.67, 95%CI: 0.49-14.45, P = 0.255) and urinary retention
      following the operation. There were an antagonistic effects (OR = 7.60, 95%CI:
      1.43-40.39, P = 0.017) of detrusor overactivity and bladder destrusor dysfunction
      on urinary retention. The multiple factors analysis results revealed that bladder
      destusor dysfunction (OR = 7.01, P < 0.01) and lack of sensation (OR = 5.45, P =
      0.018)were the independent risk factors influencing on the urinary retention post
      operation. CONCLUSIONS: There are obvious urodynamic change in cervical cancer
      patients following radical hysterectomy. Bladder destrusor dysfunction and lack
      of sensation are the independent urodynamic risk factors influencing on urinary
      retention following radical hysterectomy, while detrusor over activity may be a
      protective effect on bladder destrusor dysfunction post-operation in some degree.
      Urodynamic test is important for analysis and treatment of urinary retention
      following radical hysterectomy.

PMID- 21092549
TI  - [Effects of PTEN over-expression on phosphatidyl inositol 3-kinase/protein kinase
      B signal pathway in ovarian epithelial cancer cells].
AB  - OBJECTIVE: To evaluate the effect of exogenous wild PTEN gene stable transfected
      into human ovarian cancer cell line HO-8910 on phosphatidyl inositol 3-kinase
      (PI3K)/protein kinase B (Akt) signal pathway and cells proliferation. METHODS:
      Wild-type PTEN recombinant eukaryotic expression plasmid was constructed and then
      was transfected into HO-8910 cells by lipofectamine 2000. The expression of PTEN,
      Akt1, Akt2, PI3K mRNA and protein of PTEN were tested by reverse transcription
      (RT)-PCR and Western blot. The proliferation of HO-8910 after wild PTEN gene
      transfected was measured by methyl thiazolyl tetrazolium (MTT). RESULTS: Wild
      type PTEN gene was successfully transfected into HO-8910 cells. The results of RT
      PCR and western bolt showed that there were the significant expression high level
      of PTEN mRNA and protein after infected by wild-PTEN plasmid than those in the
      control [(17,372 +/- 23) vs. (39 +/- 1) vs. (78 +/- 4) copies/ml, P < 0.05].
      While the expression of mRNA of Akt1, Akt2 and PI3K were decreased clearly than
      those in the control [(28 +/- 2) vs. (115 +/- 5), (7 +/- 1) vs. (18 +/- 2), (61
      +/- 2) vs. (84 +/- 2) copies/ml, all P < 0.05]. The proliferation rate of HO-8910
      cells was obviously slower than those in the control (90 158 +/- 47 vs. 148,251
      +/- 65 vs. 250,115 +/- 62, P < 0.05). CONCLUSION: Transfection of PTEN may
      increase the expression of PTEN and inhibit the proliferation of HO-8910 cells,
      in which PI3K/Akt signal pathway is inhibit significantly.

PMID- 21092550
TI  - [Regulation of Bub1 mRNA expression in endometrial carcinoma Ishikawa cells by
      estrogen and paclitaxel].
AB  - OBJECTIVE: To explore the regulation of Bub1 mRNA expression in endometrial
      carcinoma cells by estrogen and paclitaxel. METHODS: The high differentiated
      endometrial adenocarcinoma cells (Ishikawa cell line) were cultured in DMED/F12
      supplemented with 10% fetal bovine serum (FBS) or phenol red-free DMED/F12
      supplemented with 5% dextran-charcoal FBS (dcFBS). Firstly, the cells were
      stimulated by 10 nmol/L estradiol (17beta-E(2)) or no hormonal stimulation as
      control group, and the cell proliferation was quantified at 24, 48 and 72 hours
      using cell counting kit-8 (CCK-8) method. Then the cells were stimulated with
      different concentrations of 17beta-E(2) (0.1, 10, 1000 nmol/L) at different
      periods (5, 15, 30 minutes and 2, 4, 8, 12, 16, 24, 30 hours), the expression of
      Bub1 mRNA was detected by real-time quantitative PCR. Ishikawa cells were
      cultured with non-serum DMEM/F12 to be synchronized, and then were treated with
      different concentrations of paclitaxel (10, 100 nmol/L) for 8 and 24 hours.
      While, non-synchronized Ishikawa cells were exposed to 100 nmol/L paclitaxel for
      different periods (4, 8, 16, 24, 48 hours), and real-time quantitative PCR was
      also used to detect the expression levels of Bub1 mRNA. Data were presented as
      folds change relative to control group, in which values < 1 were down-regulated,
      and those > 1 were up regulated. RESULTS: The proliferation rate of cells in the
      presence of 17beta-E(2) was significantly higher than that of the control group
      after treated 24 hours (A value: 0.70 +/- 0.08 vs. 0.86 +/- 0.10, P = 0.049).
      Time-dependent experiments revealed that addition of 17beta-E(2) could increase
      cell numbers during 72 hours period, while the expression level of Bub1 mRNA was
      decreased in Ishikawa cell. Dose-dependent experiments revealed maximal estradiol
      stimulation effects at 10 nmol/L (P = 0.020). After being treated with serum-free
      culture, Ishikawa cells were exposed to 10 nmol/L paclitaxel for 8 and 24 hours,
      and the expression of Bub1 mRNA decreased (0.403 +/- 0.008 vs. 0.775 +/- 0.144, P
      = 0.251). Compared to the control cells, the mRNA expression levels of Bub1 in
      cells treated by paclitaxel for 8 hours was significantly decreased (P = 0.009),
      while there was not significantly decreased at 24 hours (P = 0.396). When exposed
      to 100 nmol/L paclitaxel for 8 and 24 hours, the expression of Bub1 mRNA was also
      decreased (0.697 +/- 0.017 vs. 0.850 +/- 0.004, P = 0.061). Compared to the
      control cells, Bub1 mRNA expression was also significantly decreased (P = 0.038
      and P = 0.019, respectively). While with serum free-treatment culture, when
      Ishikawa cells exposed to 100 nmol/L paclitxel for 4, 8, 16, 24 or 48 hours, the
      expression of Bub1 mRNA significantly increased (1.127 +/- 0.105 vs. 1.614 +/-
      0.154 vs. 2.092 +/- 0.179 vs. 1.381 +/- 0.061 vs. 1.519 +/- 0.182, P = 0.002), of
      which was significantly increased at 16 hours treatment. CONCLUSION: Bub1
      expression could be regulated by estradiol and paclitaxel, in which deregulated
      Bub1 expression may contribute to chemotherapeutic efficacy of paclitaxel.

PMID- 21092552
TI  - [The importance of therapeutic evaluation on limbal stem cells transplantation].
AB  - Damage to the limbus by disease or injury would result in corneal epithelium
      defects, neovascularization and conjunctivalization, which is called limbal stem
      cells deficiency and could be treated by limbal stem cells transplantation. But
      the outcomes of surgery were much different due to various surgical techniques,
      different grade damages of recipient site and criteria for clinical evaluation
      after surgery. This article focused on reasonable evaluation methodology after
      limbal stem cells transplantation.

PMID- 21092551
TI  - [Chemotherapy resistance induced by interleukin-6 in ovarian cancer cells and its
      signal transduction pathways].
AB  - OBJECTIVE: To study the mechanism of chemotherapy resistance caused by
      interleukin-6 (IL-6) in ovarian cancer cells and its related signal pathways.
      METHODS: Ovarian cancer cell lines A2780 (IL-6 receptor positive, while non-IL-6
      expressing and cisplatin/paclitaxel-responsive) and SKOV3 cell lines
      (overexpressing of IL-6 receptor and IL-6 and cisplatin/paclitaxel-resistant)
      were suitable models for this study. The effect of exogenous (a short period of
      treatment with recombination IL-6) and endogenous IL-6 (by transfecting with
      plasmid encoding for sense IL-6) in A2780 cells or deleting of endogenous IL-6
      expression in SKOV3 cells (by transfecting with plasmid encoding for antisense IL
      6) on the sensitivity to cisplatin and paclitaxel was investigated. Meanwhile,
      the mechanism of chemotherapy resistance caused by IL-6 in ovarian cancer cells
      and its related signal pathways were also analyzed. RESULTS: We found that both
      exogenous and endogenous IL-6 induce cisplatin and paclitaxel resistance in non
      IL-6-expressing A2780 cells (the resistance multiple to cisplatin and paclitaxel
      was: exogenous, 6.25 and 7.31; endogenous, 7.13-8.34 and 7.61-10.70), while
      deleting of endogenous IL-6 expression in IL-6-overexpressing SKOV3 cells
      promotes its sensitivity to anticancer drugs (the resistance multiple to
      cisplatin and paclitaxel was 0.15 and 0.10, 0.10 and 0.08). IL-6 significantly up
      regulated the expression levels of mRNA and protein of drug resistance-associated
      genes, MDR1 and GST-pi, and apoptosis-inhibiting genes, bcl-2, bcl-xL and XIAP in
      a dose-dependent manner in A2780 cells. In accordance with this finding, the mRNA
      and protein levels of MDR1 and GST-pi enhanced in sense IL-6-transfected A2780
      cells, and reduced in antisense IL-6-transfected SKOV3 cells compared with the
      corresponding parental and control vector-transfected cells, which had no
      difference. It was found that PD98059 [mitogen-activated protein kinase
      extracellular signal-regulated kinase (MEK) inhibitor] and wortmannin
      [phosphatidylinositol 3-kinase (PI3K) inhibitor] significantly antagonized IL-6
      induced phosphorylation of extracellular signal-regulated kinase (ERK) and
      protein kinase B (Akt), respectively, and both of them blocked IL-6-induced
      cisplatin and paclitaxel resistance and the inhibitory effects of PD98059 and
      wortmannin were dependent on its concentration. CONCLUSIONS: These data suggest
      that IL-6-induced chemoresistance may be associated with increase of both drug
      resistance-associated genes (MDR1 and GST-pi) and apoptosis-inhibiting genes (bcl
      2, bcl-xL and XIAP), and activation of MEK/ERK and PI3K/Akt. Therefore,
      modulation of IL-6 expression or its related signaling pathway may be a promising
      strategy of treatment for drug-resistant ovarian cancer.

PMID- 21092553
TI  - [Focus on the challenge of basic research on corneal tissue engineering].
AB  - Great progress has been made on the corneal tissue engineering in the past two
      decades. Much knowledge has been gained on the seed cells, carrier material, and
      strategies of corneal tissue reconstruction. However, there are still great
      challenges regarding the basic research of corneal tissue engineering, such as
      selection of appropriate carrier and cells, optimization and standardization of
      the construction method, and evaluation of the clinic outcome. Future studies may
      address these questions and bring tissue engineered cornea into clinic
      application.

PMID- 21092554
TI  - [Limbal allografting from related live donors for limbal stem cell deficiency
      secondary to ocular chemical burn].
AB  - OBJECTIVE: To investigate the efficacy and complications of limbal allografting
      from related live donors (RL-LAT) for limbal stem cell deficiency secondary to
      ocular chemical burn. METHODS: Retrospective comparative case series. Limbal
      allografting from related live human leukocyte antigen (HLA)-matched (n = 10) and
      unmatched donors (n = 2) was performed in 12 consecutive patients (12 eyes) with
      limbal stem cell deficiency secondary to ocular chemical burn, including 9 alkali
      burn and 3 acid burn; whereas allolimbal cadaver transplant was performed in
      another 15 patients in Zhongshan Ophthalmic Center between April 2006 to December
      2007. Systemic cyclosporine A was administered to later eight recipients in
      living related donor group and all patients in cadaver donor group. Main outcome
      measures were restoration of corneal epithelium, reduction in corneal
      vascularization, improved corneal clarity, and visual improvement. Mean follow-up
      was (11.4 +/- 3.6) months (from 12 to 27). RESULTS: In living related donor
      group, ten patients (83.3%) achieved initially reepithelialize, and epithelial
      healing time was (9.6 +/- 3.4) d. Nine patients (75.0%) achieved stable ocular
      surface (stable corneal epithelium, decreased vascularization of corneal surface,
      and reduced corneal opacification). However, in seven eyes (77.8%) achieved
      stable ocular surface, gradual recurrence of peripheral corneal vascularization
      occurred after 5 to 8 months postoperatively. Whereas in cadaver donor group,
      twelve patients (80.0%) achieved initially reepithelialize, and epithelial
      healing time was (11.2 +/- 4.6) d. Seven patients (46.7%) achieved stable ocular
      surface. However, in all seven eyes achieved stable ocular surface, gradual
      recurrence of peripheral corneal vascularization occurred after 4 to 10 months
      postoperatively. The differences of both the rate of initially reepithelialize
      and epithelial healing time between these two groups showed no statistical
      significance (chi(2) = 1.764, P = 0.117; t = 0.116, P = 0.133, respectively).
      However, the differences of both the successful rate of ocular surface
      reconstruction and the recurrent rate of corneal vascularization during the
      follow-up period between these two groups were statistically significant (chi(2)
      = 4.158, P = 0.015; chi(2) = 3.463, P = 0.022, respectively). In living related
      donor group, features of graft rejection developed in two patients with
      postoperative stable ocular surface, Both rejected recipients had one among HLA
      matched and one among-unmatched respectively. Whereas in cadaver donor group,
      features of graft rejection developed in three patients with postoperative stable
      ocular surface. None of the donor eyes had any complications. CONCLUSIONS: Limbal
      allografting from related live donors is more effective to reconstruct the ocular
      surface of limbal stem cell deficiency secondary to ocular chemical burn than
      allolimbal cadaver transplant. HLA-matched limbal allografting could reduce
      postoperative graft rejection and systemic cyclosporine A is useful in ensuring
      long-term survival.

PMID- 21092555
TI  - [Retrospective analysis of ocular cicatricial pemphigoid].
AB  - OBJECTIVE: To analyze the clinical characterization of ocular cicatricial
      pemphigoid (OCP). METHODS: It was a retrospective series case study. Five
      consecutive patients referred for the evaluation of possible OCP from January
      2005 to October 2008 in Departments of Ophthalmology and Dermatology of Peking
      University First Hospital. History and clinical characterization of 5 cases (10
      eyes) OCP having been misdiagnosed were analyzed to find the causes of
      misdiagnosis. RESULTS: All of cases were diagnosed as chronic conjunctivitis
      during the early stages of the diseases, one case was diagnosed as Stevens
      Johnson syndrome and one as Sjogren syndrome during the later stage. It was two
      to five years from the first time to see a doctor to definite diagnosis. All of
      cases have been prescribed antibiotic eye drops for a long times, one case has
      been undergone three times trichiasis operation and made the disease progression.
      Among the five patients with OCP, 3 eyes were diagnosed Stage II, 5 eyes Stage
      III, 2 eyes Stage IV. Three cases were positive of bacterial culture. Only in 1
      case, there was slight increase of iron protein as tumor mark. Inflammation was
      controlled by the end of the study, but cicatrization of 2 cases still
      progressed. CONCLUSION: Manifestation of OCP can mimic chronic conjunctivitis
      during the early stages, it is important to pay high attention to OCP,
      misdiagnosis may be stopped.

PMID- 21092556
TI  - [Preliminary investigation on tear film alterations in latent herpes stromal
      keratitis].
AB  - OBJECTIVE: To investigate tear film alterations in patients with latent herpes
      stromal keratitis (HSK). METHODS: Prospective comparative case series study.
      Twenty-four patients with latent HSK in one eye and 28 age and gender matched
      healthy individuals were recruited. All subjects were evaluated by subjective
      symptoms of dry eye, tear film break-up time (BUT) and Schirmer I test (SIT).
      Laser in vivo confocal microscopic investigation was performed in 12 patients
      with severe tear film instability (BUT <= 5 s). Data distribution and homogeneity
      of variance was analyzed. Statistical comparisons of the mean values between
      different groups were performed using Kruskal-Wallis test, Mann-Whitney test or
      student t-test. RESULTS: Most of latent HSK patients (n = 22/24, 91.7%) had
      symptoms as dryness, burning sensation, redness and foreign body sensation. Both
      eyes of patients with latent HSK had hyposecretion (SIT, control eyes (16.2 +/-
      3.2) mm/5 min; affected eyes (10.4 +/- 7.8) mm/5 min; lateral eyes (11.2 +/- 8.8)
      mm/5 min; control and affected, U = 135.0, P < 0.001; control and lateral, U =
      155.0, P = 0.001) and decreased tear film stability [BUT, control eyes (12.1 +/-
      0.7) s, affected eyes (4.3 +/- 3.3) s, lateral eyes (9.2 +/- 4.4) s; control and
      affected, U = 28.0, P < 0.001; control and lateral, U = 114.0, P < 0.001] as
      compared to control group (Kruskal-Wallis nonparametric test). The value of BUT
      showed significant difference between affected eyes and healthy eyes (U = 90.0, P
      < 0.001), whereas no difference of the value of SIT was found (U = 273.0, P =
      0.757). Abnormal SIT (<= 10 mm/min) and BUT (<= 10 s) was presented in 14 (58.3%)
      and 23 (95.8%) affected eyes, as well as in 14 (58.3%) and 17 (70.8%) lateral
      eyes, respectively. Laser in vivo confocal microscopy investigation in 12
      affected corneas with abnormal tear film showed morphological alterations as
      corneal epithelial metaplasia with polymorphism and enlarged cells, reflective
      nuclei, and decreased nucleus/cytoplasm ratio; decreased nerve density in
      subepithelial plexus and obvious branching and beading, which is similar to those
      changes caused by dry eye. CONCLUSIONS: Most of latent HSK patients had abnormal
      tear film. Dry eye related alterations could be found in affected corneas with
      abnormal tear film by in vivo confocal microscopy.

PMID- 21092557
TI  - [Analysis of changes of ultrasonic image and hemodynamics of retrobulbar blood
      vessels in Coats disease].
AB  - OBJECTIVE: To analyze the changes of color Doppler flow imaging (CDFI) and
      hemodynamics of retrobulbar blood vessels in Coats disease. METHODS: It was a
      prospective and self-comparative study in which 18 cases (18 eyes) were included.
      Axial eye length was measured with A scan. Routine CDFI was performed in all
      cases. We examined ophthalmic arteries (OA), central retinal arteries (CRA) and
      posterior ciliary arteries (PCA) by CDFI, and recorded the peak systolic
      velocities (PSV), end diastolic velocities (EDV), time averaged maximum
      velocities (TAMX), pulsatility indexes (PI) and resistance indexes (RI) in all
      cases. Each hemodynamic parameter in the affected eye (21.36 +/- 1.19) mm was
      compared with those in the contralateral normal eye (controls). T-test was used
      for the estimation of significance of the difference between the diseased and
      normal eyes. RESULTS: The axial length in diseased eyes was significantly shorter
      than that of the controls (22.92 +/- 1.09) mm (t = 3.617, P < 0.05). The changes
      of CDFI in diseased eyes included retinal detachment, retinal cyst, subretinal
      organization, etc. Vitreoretinal traction, intraocular ossification and
      calcification were uncommon. The PSV (6.96 +/- 1.21) cm/s and EDV (1.99 +/- 0.36)
      cm/s in the diseased eyes were significantly lower than the PSV (8.30 +/- 1.46)
      cm/s and EDV (2.48 +/- 0.47) cm/s in the control eyes (t = 2.995, 3.476;P <
      0.05). No significance difference was present in other hemodynamic parameters
      between diseased and normal eyes. CONCLUSIONS: Coats disease is a congenital
      disease that may influence the development of the eye. The ultrasonography is
      helpful for the diagnosis and differential diagnosis in Coats disease. Low
      perfusion of the central optic artery might exist in Coats disease. The
      hemodynamics changes in Coats disease require further studies.

PMID- 21092558
TI  - [VCR-loaded nanoparticles as targeted delivery system for the treatment of
      orbital adenoid cystic carcinoma].
AB  - OBJECTIVE: To prepare and observe the properties of Folate Receptor-mediated VCR
      loaded nanoparticles, which is abbreviated as FA-PLGA (VCR)-NP and to study the
      inhibitory effect of FA-PLGA (VCR)-NP in ACC-2 cells in vitro and in ACC in
      BALB/c-nu mice. METHODS: The mAified W/O/W extraction-evaporation technique was
      chosen to prepare FA-PLGA (VCR)-NP. Tumor cells were divided into three groups:
      VCR, PLGA (VCR)-NP and FA-PLGA (VCR)-NP. Seven doses (0.05, 0.25, 0.50, 1.00,
      5.00, 10.00, and 30.00 mg/L) of VCR were tested in the cell culture mAel. After
      1, 2, 3, 4 and 5 days, the cell growth inhibition ratio was evaluated by MTT
      colorimetry. Nude mice mAel of orbital ACC was built by injecting ACC cell
      suspension and divided into four groups: VCR, PLGA (VCR)-NP, FA-PLGA (VCR)-NP,
      and control group. After 1 day, 7 days and 14 days, the inhibition ratio of gross
      tumor volume was observed. Residual concentrations of VCR in tumors were
      evaluated by HPLC. The feature of histopathology was observed by electron
      microscopy. The effect of empty nanoparticles on ACC-2 cells was compared with
      normal control group using t-test to analyze. On account of different drugs,
      concentration, time and the interaction of them, multivariate analysis of
      variance was used to analyze their relationship. Inhibition rate and residual
      volume of drug concentrations were compared using one-factor analysis of variance
      and LSD method. RESULTS: FA-PLGA (VCR)-NP were smooth and spherical with a mean
      particle size of 249.2 nm. The drug loading efficiency was 4.53%. The release of
      VCR from PLGA nanoparticles can persist for 14 d. After blank particles PLGA-NP
      and ACC-2 cells were co-cultured for 5 days, cell viability had remained at more
      than 80 percent (t = 1.952 ~ 3.285, P = 0.081 ~ 0.190). The inhibitory effect of
      FA-PLGA (VCR)-NP was more effective than VCR alone after a period of time (F =
      4.798 ~ 563.479, P = 0.000 ~ 0.006). The effects of the treatment were both in
      dose-dependent and time-dependent manner. Targeting particles could attach to
      tumor surface, via folate receptor. FA was competitive inhibitor of this
      recolonization. The volume inhibition ratios of FA-PLGA (VCR)-NP and PLGA (VCR)
      NP were significant higher than VCR (P = 0.016, P = 0.029). The inhibition ratio
      of FA-PLGA (VCR)-NP was higher than that of PLGA (VCR)-NP, but there was no
      statistical difference (P = 0.376). There was significant different between
      residual concentrations of VCR on the 1(st), 7(th) and 14(th) days. TEM pictures
      showed a mass of electron-dense microspheres in tumor cells on the 14(th) day.
      Tumor necrosis was obvious, while surrounding tissues were normal. CONCLUSIONS:
      FA-PLGA (VCR)-NP are stable and have high drug entrapment efficiency and high
      effect of growth inhibition in vitro. It can be proposed as a potentially
      controlled and targeted delivery system for the treatment of ACC.

PMID- 21092559
TI  - [Protective effect of minocycline on glutamate-induced retinal ganglion cell
      injury and molecular mechanism].
AB  - OBJECTIVE: To investigate the protective effect and molecular mechanism of
      minocycline on toxicity of retinal ganglion cells induced by L-glutamate.
      METHODS: Primary mouse retinal ganglion cells (RGC) were isolated from mouse
      retinal in vitro. RGC were divided into control group, L-glutamate group, and L
      glutamate + minocycline group, the cell survival rate and nerve axon growth
      length were observed. In vivo study, B6 mice was intravitreal injected with 2 ul
      L-glutamate (2 mmol/L) to construct a toxic damage to retinal ganglion cells
      animal model. One day before the beginning of the experiment, mice were daily
      intraperitoneal injected with minocycline (60 mg/kg, saline injected in the
      control group) till day 7, beta3 tubulin positive cells and retinal GFAP protein
      expression were evaluated by tissue i mmol/L unofluorescence assay. Real-time PCR
      and Western blot assay were used to detect IFN-gamma, IL-1, TNF-alpha and GFAP
      and vimentin mRNA and protein expression level in retinal tissues. RESULTS:
      Compared with control group, RGC survival rate in L-glutamate group was
      significantly reduced with a dose-and time-dependent. In addition, axon growth
      was inhibited with the treatment of glutamic acid, while these effects were
      abolished in the minocycline group (F = 18.87, P < 0.01). Animal study showed
      that the number of RGC dramatically decreased, however, expression of GFAP in
      retinal tissue significantly increased in L-glutamate treated mice, compared to
      control (F = 7.6, P < 0.01). Minocycline treatment significantly improved L
      glutamate-induced ganglion cell damage and significantly reduced their GFAP
      expression. Both mRNA and protein expression levels of IFN-gamma, IL-1, TNF-alpha
      and GFAP and Vimentin in retinal tissue of L-glutamic acid group significantly
      upregulated compared to control, while the minocycline significantly reduced the
      expression of these factors. CONCLUSIONS: L-glutamic acid can induce retinal
      ganglion cells damage, inhibit axon growth and increase inflammatory and glial
      cell related genes and proteins expression. Minocycline could significantly
      protect retinal ganglion cells from the injury caused by L-glutamate.

PMID- 21092560
TI  - [Expression of immediate-early genes in primary visual cortex of rat early after
      acute optic nerve injury].
AB  - OBJECTIVE: To investigate the differential expression of immediate-early genes c
      jun and c-fos in primary visual cortex of rat early after acute optic nerve
      injury and the relationship between immediate-early gene expression and injury
      degree of optic nerve. METHODS: This was an factorial design of two factors. 55
      male Sprague-Dawley rats were divided into groups randomized. Unilateral optic
      nerve crush injury or transection was performed in rats to obtain acute partial
      or complete monocular optic nerve injury models. Frozen sections through visual
      cortex were cut in normal rats and model rats respectively at 2 h, 1 d, 3 d, 1
      week and 1 month after operation. Expression of c-Jun and c-Fos was detected in
      primary visual cortex by means of immunohistochemistry. Statistical comparisons
      were made using variance analysis of factorial design. RESULTS: Statistically
      significant different of c-Jun expression existed between optc nerve crash injury
      and transection models (F = 50.344, P = 0.000). Increased expression of c-Jun in
      primary visual cortex could be observed at 2 h postoperation, and reached peak
      value at 1d postoperation. The extent of increased c-Jun expression was much
      higher in optic nerve transection models than crush injury models. Statistically
      significant different of c-Fos expression existed between optc nerve crash injury
      and transection models (F = 62.232, P = 0.000) Decreased expression of c-Fos in
      primary visual cortex could be observed at 2 h postoperation in optic nerve crush
      injury models, and reached bottom at 3 d postoperation. The extent of decrease of
      c-Fos expression was lower in optic nerve transection models than crush injury
      models and transient increased expression could be observed at 2 h postoperation.
      CONCLUSIONS: The expression of immediate-early genes c-Jun and c-Fos changed
      shortly after optic nerve injury. They may act in opposite direction in the
      primary visual cortex.

PMID- 21092561
TI  - [Biocompatible study of modified titanium skirt for keratoprosthesis].
AB  - OBJECTIVE: The research is engaged in developing an improved titanium skirt for
      keratoprosthesis, the aim of this study was to evaluate biocompatible of
      keratoprosthesis of novel design. METHODS: The pure titanium skirt for
      keratoprosthesis with three hands were first Sandblasted, and then bioactive
      hydroxyapatite coated on Sandblasted titanium for keratoprosthesis by a acid
      alkali chemical treatment. A total of 18 New Zealand white rabbits and 18 alkali
      burned rabbit corneas were respectively divided into three groups (Group A, B and
      C; Group E, F and G) with simple random sampling methods. The modified titanium
      skirt was inserted into the corneal stroma of Group A and E, and then the control
      skirt was inserted into Group B and F. Group C and H did not insert skirt as
      surgery control. The interfacial biointegration of skirt/cornea were examined
      under light microscopy by HE, TEM and SEM. The transparent center was implanted
      to rabbit corneas with modified titanium skirt after 3 months. RESULTS: Dense
      hydroxyapatite coating was deposited on the Sandblasted specimens by an acid
      alkali chemical treatment. The number of corneal fibroblasts increased
      significantly in Group A compared with Group B. The extracellular matrix
      deposited on the surface of modified titanium skirt was more dense and tight than
      that of control skirt. There was a significant difference in the shear force of
      skirt among groups A and B (t = 3.297, P < 0.05), E and F (t = 4.237, P < 0.05),
      and taking out the skirt in Group A and E were more difficulty than that in Group
      B and F after 3 months. The observation of the tissue sections of modified skirt
      inserted eyes revealed that there were cells and collagen-like fibres
      perpendicular to or at an angle to the rough interface and the cellular function
      was extremely active, in accordance with the results of TEM. Compared with
      healthy host tissue, skirt/cornea healing after alkali burn was impaired.
      CONCLUSIONS: Hydroxyapatite modified Sandblasted titanium skirt for
      keratoprosthesis can promote the interfacial biointegration of skirt and host
      cornea, no matter in healthy cornea or diseased cornea (alkali burn cornea).
      Hydroxyapatite coating improved the bioactivity of titanium.

PMID- 21092562
TI  - [Expression of inflammatory cytokines in a mouse model of keratomycosis].
AB  - OBJECTIVE: To investigate the expression, contribution and regulation of
      predominant inflammatory cytokines in the inflammation process of in a mouse
      model of keratomycosis. METHODS: It was an experimental study. Two hundred forty
      inbred BALB/c mice were randomly divided into four groups (injury control group,
      F. solani infected group, A. fumigatus infected group and C. albicans infected
      group) and establishment fungal keratitis was performed. At 1, 3, 5, and 7 days
      after infection, the photographs of their corneas were taken using the slit lamp
      and the digital camera system. The presence of inflammatory cells and fungal
      hyphae were observed by HE and PAS staining. Four inflammatory cytokines in
      infectious corneas, including MIP-2, KC, IL-1beta, and IL-6, were detected
      respectively for expression of mRNA and protein levels, using RT-PCR and ELISA.
      One-way ANOVA was used to test the comparisons of the clinical scoring, RT-PCR,
      and ELISA, and LSD was used to test multiple comparisons. RESULTS: The course and
      inflammatory reaction of corneal tissue in all infected group increased at day 3
      and 5 and gradually decreased after day 7 with time. The RT-PCR results showed,
      the mRNA expression levels of MIP-2 and IL-1beta were the highest in A. fumigatus
      infected group, and the expression levels of KC was the highest in C. albicans
      infected group. Additionally, the expression levels of IL-6 were found to be the
      highest in F. solani infected group. The mRNA expression levels of IL-1beta and
      KC in each experimental group were higher than those of IL-6 and MIP-2. The peak
      expression levels of MIP-2, KC, and IL-1beta occurred at day 5, day 1, and day 3
      in F. solani infected group, A. fumigatus infected group and C. albicans infected
      group, respectively. However, the peak expression level of IL-6 occurred at day 1
      and 7, day 1 and 7, and day 1 and 5 in the F. solani, A. fumigatus, and C.
      albicans groups, respectively. The difference of mRNA expression of each cytokine
      had statistically significant between each groups (MIP-2: F = 1675.339, P < 0.01;
      KC: F = 730.267, P < 0.01; IL-1beta: F = 297.106, P < 0.01; IL-6: F = 174.513, P
      < 0.01). The protein expression levels of the four cytokines in the infected
      groups from high to low in turn were IL-1beta, MIP-2, KC and IL-6. The trend of
      protein expression of the four cytokines at each time point was the same as the
      cytokine mRNA expression in different experimental groups as well as within the
      same group. The difference of protein expression of each cytokine had
      statistically significant between each groups (MIP-2: F = 2871.736, P < 0.01;
      KC:F = 886.598, P < 0.01; IL-1beta: F = 3595.488, P < 0.01; IL-6: F = 89.225, P <
      0.01). CONCLUSIONS: The expression levels of MIP-2, KC and IL-1beta are closely
      related to the performance of the disease severity and inflammatory reaction of
      FK. The expression of MIP-2 and IL-1beta may play important role in the
      pathogenesis of FK.

PMID- 21092563
TI  - [Pathological study of mycobacterium abscessus keratitis].
AB  - OBJECTIVE: To characterize the cytopathology, histopathology,
      immunohistochemistry and ultrastructural organization features of Mycobacterium
      abscessus keratitis. METHODS: This retrospective case report included six cases
      with the lesions tissues scraped from acute phase of mycobacterium abscessus
      keratitis after corneal foreign body removal. Among the 6 scrapings, 4 were
      tested for Ziehl-Neelsen acid-fast staining and 3 were examined by transmission
      electron microscopy (TEM). The corneal tissues of 2 cases in chronic phase of the
      disease were collected during keratoplasty and were examined by pathological
      examination including hematoxylin-eosin (HE) staining, acid-fast staining,
      immunohistostaining and TEM. RESULTS: A single or fascicular red bacilli were
      observed after acid-fast staining in the four cases of corneal scrapings. The
      smear samples contained a large number of neutrophils and necrotic corneal
      epithelium and stroma tissue accompanying with a large number of mycobacteria
      that were positive for acid-fast staining scattered in and out of inflammatory
      cells. The corneal buttons obtained at keratoplasty in the 2 patients
      demonstrated corneal epithelial hyperplasia, stroma degeneration, necrosis and
      exelcosis, neutrophil and lymphocyte infiltration, neovascularization and fibrous
      hyperplasia, but no positive mycobacteria by Ziehl-Neelsen acid-fast staining.
      There were no CD4(+) or CD8(+) cells from immunohistochemistry examination. TEM
      of the corneal scrapings of the 3 cases showed phagocytosis of mycobacterium
      abscessus in mononuclear macrophage or neutrophils, inclusion compounds of small
      vacuoles and metachromatic granules in the thallium. TEM of corneal buttons of 2
      cases showed slender rod-shaped mycobacteria with several to dozens of finely
      ground particles with high electron-dense, but no cell wall (L-form) or inclusion
      compounds. CONCLUSIONS: Mycobacterium abscessus keratitis presents acute purulent
      inflammatory changes in early stage and advances to chronic and non-specificity
      inflammation changes in late stage. L-formed mycobacterium abscessus make the
      disease protraction.

PMID- 21092564
TI  - [Expression of integrin during the course of adhesion between fungi and corneal
      epithelial cells].
AB  - OBJECTIVE: To investigate the expression of integrin during the course of
      adhesion between fungi and corneal epithelial cells. METHODS: It was an
      experimental study. Human corneal epithelial cells were cultured and the adhesion
      model were established between human corneal epithelial cells and Fusarium solani
      (CGMCC 3.1829) or Aspergillus fumigatus (CGMCC 3.0772) in vitro. Human corneal
      epithelial cells were incubated with Fusarium solani or Aspergillus fumigatus at
      37 degrees C and the non-adhered fungi were washed out with sterile phosphate
      buffered solution (PBS). The total RNA was extract from the human corneal
      epithelial cells. Real-time polymerase chain reaction (RT-PCR) for the expression
      of integrin was performed. RESULTS: The results of RT-PCR showed that during the
      course of adhesion between Aspergillus fumigatus and corneal epithelial cells,
      the expression of integrin alpha L (ITGAL), integrin alpha M (ITGAM), integrin
      alpha X (ITGAX) and integrin beta 2 (ITGB2) were upregulated significantly.
      However, during the course of adhesion between Fusarium solani and corneal
      epithelial cells, there was no significant differences in the expression of those
      14 kinds of integrin. CONCLUSIONS: Integrin alphaLbeta2, alphaMbeta2 and
      alphaXbeta2 are all belong to the leukocyte adhesion receptor group (beta2 group)
      in integrin family. These three members are all involved in the adhesion of
      Aspergillus fumigatus and corneal epithelial cells. With the adhesion, the
      expression of integrin is upregulated. These results suggest that the integrin
      mediated adhesion is different with different kinds of fungi. Integrin plays an
      important role in adhesion of fungi with human corneal epithelial cells.

PMID- 21092565
TI  - [Substance P and corneal wound healing].
AB  - Cornea is one of the sites that have many nerve fiber terminals which play
      critical roles in maintaining normal cornea functions and the wound healing of
      cornea. SP is one of the neurotransmitters released by cornea nerve fiber and is
      very important in signal transduction and feedback control of the cornea. The
      relationship between SP and cornea wound healing has been discussed.

PMID- 21092566
TI  - [Recent advances in tuberculous uveitis].
AB  - With an increasing number of new cases of tuberculosis every year, the incidence
      of tuberculous uveitis presents a rising trend. The disease is associated with a
      wide spectrum of clinical manifestations. The common clinical presentations
      appear to be anterior uveitis, choroidal tubercles, multifocal choroiditis,
      rarely serpiginous-like choroiditis, subretinal abscesses or suspected ocular
      tumors. Macular edema can be the only ocular manifestation of tuberculosis. With
      absence of proper diagnostic standard, it usually leads to missed diagnosis,
      misdiagnosis, and delayed diagnosis of tuberculous uveitis which can result in
      severe consequences such as vision loss, blind, and even eye enucleation. New
      technology such as PCR and Interferon-Gamma release assays can be helpful for the
      diagnosis of tuberculous uveitis. The early diagnosis and standard treatment of
      tuberculous uveitis are in urgent need.

PMID- 21092567
TI  - [Development and challenges of pancreatic surgery].

PMID- 21092568
TI  - [Current clinical research of pancreatic cancer should pay attention to several
      issues].

PMID- 21092569
TI  - [Mastering the treatment acute pancreatitis proceeding from the guideline].

PMID- 21092571
TI  - [A new method for integrated radical resection of uncinate process of the
      pancreas: a report of 306 cases].
AB  - OBJECTIVE: To investigate the methods and skills of integrated radical resection
      of uncinate process of the pancreas for patients with periampullary malignant
      tumor. METHODS: From March 2005 to March 2010, 306 cases of radical
      pancreaticoduodenectomy (RPD) of periampullary malignant tumor had been
      continuously performed. By exchanging superior mesenteric artery and controlling
      blood stream of pancreatic uncinate process, the integrated radical resection of
      uncinate process for these patients had been successfully completed. Deal with
      restitution of alimentary tract by all using Child method. The method of simplify
      binding pancreaticojejunostomy was carried out to pancreatico-jejunal
      anastomosis. The cases included 169 male and 137 female with 37 - 79 years old,
      and the mean age was 58 years. Tumor types included 151 pancreatic head and neck
      tumors, 48 distal bile duct tumors, 55 ampullary tumors and 52 duodenal papilla
      tumors. RESULTS: Among the 306 cases with RPD, operation time were 4 - 6 h and
      the blood loss were 200 - 600 ml with no intraoperative and postoperative
      bleeding of pancreatic uncinate process site. The incidence rates of
      postoperative bleeding and mortality were 3.3% and 0.9% respectively. The
      incidence rates of postoperative pancreatic fistula and biliary fistula incidence
      were 1.6% and 0.6% respectively. And patients with fistula had well recovered by
      expectant treatment of ultrasound-guided puncture and drainage. Follow-up to
      March 2010, there were no patients died from the recurrence of superior
      mesenteric vascular tumor. CONCLUSIONS: By exchanging superior mesenteric artery
      and controlling blood stream of pancreatic uncinate process, the integrated
      radical resection of uncinate process for those patients who have periampullary
      malignant tumor can be successfully completed. It can reduce the operating
      bleeding, operating time and the miscut of superior mesenteric vein and(or)
      superior mesenteric artery, it can avoid postoperative pancreas necrosis off,
      infection and hemorrhage caused by the pancreas uncinate process residues, and it
      also theoretically reduces the chance of tumor cells spreading.

PMID- 21092570
TI  - [Indications, technique and efficacy of organ preserving pancreatectomy].
AB  - OBJECTIVE: To discuss the proper surgical management of pancreatic benign and low
      grade malignant potential neoplasm. METHODS: The experience of 72 cases who
      accepted organ preserving pancreatectomy from January 1990 to May 2010 was
      analyzed retrospectively. There were 24 male and 48 female, aged from 15 to 68
      years with mean age of 46 years. There were 9 cases underwent duodenum-preserving
      resection of the head of the pancreas, 29 cases underwent spleen-preserving
      distal pancreatectomy, 11 cases underwent middle segmental pancreatectomy, 23
      cases underwent tumor extirpation of huge pancreatic cancer in pancreatic head
      and body. RESULTS: Pancreatic fistula and biliary fistula in 1 case respectively
      were cured among who accepted duodenum-preserving resection of the head of the
      pancreas. Pancreatic fistula was found in 3 cases who accepted spleen-preserving
      distal pancreatectomy. Pancreaticobiliary anastomotic bleeding in 1 case was
      cured among who accepted middle segmental pancreatectomy. Pancreatic fistula was
      found in 5 cases among who accepted tumor extirpation of huge pancreatic cancer
      in pancreatic head and body, and liver metastasis was found in 3 cases at 6, 12,
      16 months after surgery respectively. CONCLUSIONS: Organ preserving
      pancreatectomy can obviously reduce operative injury to patients, its therapeutic
      effect is similar to that of classical operation, it is the first option of
      benign and low-grade malignant potential neoplasm.

PMID- 21092572
TI  - [Experience of the surgical comprehensive treatment on severe acute
      pancreatitis].
AB  - OBJECTIVE: To summary the experience of the surgical comprehensive treatment of
      severe acute pancreatitis (SAP). METHODS: From July 1999 to December 2009, a
      total of 506 patients suffered SAP were admitted with a mean APACHE II score 12.8
      +/- 4.6. There were 270 male and 236 female, aged from 16 to 89 years, mean age
      43 years. SAP patients were treated by the SAP treatment team which consisted of
      pancreatic specialized and multidisciplinary doctors. Two hundreds and thirty
      four cases (46.2%) received non-operative treatment and 272 cases (53.8%)
      received surgical intervention. RESULTS: In 506 cases, 445 patients were cured
      and 52 patients died (31 died in early stage, 21 died in later stage), 9 cases
      discharged automatically. The overall incidence of complication, overall
      mortality and overall curative rate were 29.4% (149/506), 10.3% (52/506) and
      87.9% (445/506), respectively. The incidences of complication in non-operative
      group and in surgical intervention group were 27.8% (65/234) and 30.9% (84/272),
      respectively (P > 0.05). The mortality in non-operative group and in surgical
      intervention group were 9.4% (22/234) and 11.0% (30/272), respectively (P >
      0.05). The curative rates in non-operative group and in surgical intervention
      group were 90.6% (212/234) and 85.7% (233/272), respectively (P > 0.05).
      CONCLUSIONS: Patients should be treated in ICU in the early phase of the disease
      when APACHE II score > 10. Pancreatic specialized and multidisciplinary team
      treatment, appropriate choice of timing, indication and procedure of surgical
      intervention and details of drainage are vital to the prognosis of SAP.

PMID- 21092573
TI  - [The clinical effectiveness of percutaneous drainage and laparotomy for patients
      with infective pancreatic necrosis].
AB  - OBJECTIVE: To compare the clinical effectiveness of percutaneous US- or CT-guided
      drainage and laparotomy for patients with infective pancreatic necrosis. METHODS:
      Data of 90 infective pancreatic necrosis patients admitted from January 2008 to
      December 2009 were included. They were divided into two groups by the different
      treatment choices. Twenty-seven patients in the percutaneous group received
      percutaneous US- or CT-guided drainage as first choice. After that a sump suction
      apparatus was applied for controlled drainage. If no improvement was achieved
      after 3 days, they would received operation soon. While patients in the
      laparotomy group received surgical drainage at the time when the diagnosis of
      infected pancreatic necrosis was confirmed. Continuous drainage was also applied
      for these ones. RESULTS: The percutaneous group had a significant low rate of
      reoperation (7.1% vs. 14.3%, P < 0.05) and postoperative residual abscesses (7.1%
      vs. 28.6%, P < 0.05). Furthermore, 48.1% of patients in percutaneous group
      successfully avoid laparotomy. In the regard of complications, the percutaneous
      group presented lower incidence of both single organ dysfunction (7.4% vs. 28.6%,
      P < 0.05), intestinal fistula (7.4% vs. 27.0%, P < 0.05) and long-term
      complications (3.7% vs. 22.2%, P < 0.05). In addition, the percutaneous group
      costed less medical resources as evidenced by shorter ICU duration (21.2 +/- 9.7
      vs. 28.7 +/- 12.1, P < 0.01), shorter hospital duration (48.2 +/- 12.5 vs. 59.6
      +/- 17.5, P < 0.05) and less expenditure (191 762 +/- 5892 vs. 341 689 +/- 10
      854, P < 0.05). CONCLUSIONS: Percutaneous drainage can effectively lower the
      surgical rates and the rates of complications and reoperations in patients with
      infective pancreatic necrosis. Besides that, it could also reduce the cost of
      medical resources.

PMID- 21092574
TI  - [Surgical complications after pancreatoduodenectomy: risk factors and
      treatments].
AB  - OBJECTIVE: To explore the impact factors and treatment of post
      pancreatoduodenectomy complications. METHODS: The clinical data of 412 cases
      between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed
      retrospectively. There were 232 male, 180 female. Univariate and multivariate
      logistic regression model were used to identify the risk factors related to
      occurrence of postoperative complications. RESULTS: The overall postoperative
      morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total
      uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter
      and pancreatic texture had effects on postoperative pancreatic fistula
      statistically. Total uncinate process resection, the amount of intra-operative
      blood loss >= 600 ml and pancreatic fistula were identified as significant risk
      factors for post pancreatoduodenectomy hemorrhage by means of univariate
      analysis. Delayed gastric empting occurrence in the patients with pylorus
      preserving pancreaticoduodenectomy was higher than those with standard
      pancreaticoduodenectomy significantly. The multivariate Logistic regression
      analysis revealed that duct diameter and pancreatic texture were the independent
      risk factors of pancreatic fistula. Total uncinate process resection, the amount
      of intra-operative blood loss >= 600 ml and pancreatic fistula were independent
      risk factors of bleeding. There were no statistically significant differences
      between the radical group and the standard group when postoperative complication
      rates were analyzed (P < 0.05). CONCLUSIONS: Pancreaticojejunal anastomoses by
      means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and
      end-to-end invaginated pancreaticojejunostomy is fit for the patients with
      undilated pancreatic duct. The prevention of postoperative bleeding depends on
      total uncinate process resection and meticulous hemostatic technique during
      operation. The pancreatic fistula is one of the most important factors which can
      result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV
      resection and extended lymphadenectomy do not significantly increase the
      morbidity rates.

PMID- 21092575
TI  - [Surgical treatment strategy for malignant pancreatic neuroendocrine tumor].
AB  - OBJECTIVE: To investigate the surgical options for the malignant pancreatic
      neuroendocrine tumor (PNETs). METHODS: The clinic data of 32 patients with
      malignant pancreatic neuroendocrine tumors who were admitted between January 2003
      and December 2009 were summarized. There were 19 male and 13 female, aging from
      17 to 71 years (mean age, 46.3 years). The general information, postoperative
      pathology results, surgical options and followup were also collected. RESULTS:
      There were 32 cases of malignant PNETs including functional malignant PNETs in 12
      cases and nonfunctional malignant PNETs in 20 cases. Thirty-one patients accepted
      surgical treatments which included local resections in 4 patients, Whipple
      procedures in 7 patients, distal pancreatectomy in 17 patients and laparotomy in
      3 patients. One patient accepted CT guided biopsy. Follow up were lost in two
      patients after operations. Five patients died in the first year after operations.
      Twenty-two patients still survived after mean follow up of 28 months (4 - 83
      months). The survival rate for this group of patients was 83.5% in the first
      year, 72.6% in the second year and 54.4% in the fifth year. CONCLUSIONS:
      Malignant PNETs is the proper indication for surgical treatments. More
      accumulation of clinical data is needed to evaluate the significance of local
      resection of malignant PNETs in pancreatic head and cytoreductive surgery.

PMID- 21092576
TI  - [Middle segment pancreatectomy for the benign tumors of the neck and body of the
      pancreas (report of 15 cases)].
AB  - OBJECTIVE: To study the clinical application value of middle segment
      pancreatectomy in the treatment of benign tumors of the amphi-neck of the
      pancreas. METHODS: Fifteen cases were retrospectively analyzed treated from
      November 2005 to June 2009. There were 3 male and 12 female aging from 30 to 50
      years. They all received middle segment pancreatectomy for benign tumors of the
      amphi-neck of the pancreas. RESULTS: There was no death during perioperative
      period. All the 15 patients received middle segment pancreatectomy. Fourteen of
      them received the closure of broken ends of pancreatic head,
      pancreaticojejunostomy (mono-anastomosis) and the rest one received dipl
      anastomosis. Postoperative pathology showed that in the 15 patients, 1 got solid
      pseudopapillary tumor of the pancreas, 3 got non-functional islet cell tumor, 11
      got cystadenoma of pancreas. Three of them got pancreatic fistula and were self
      cured in 3 months. Follow-up visits to all the patients kept in the following 2
      to 45 months. There was no death. No patients got new-onset diabetes and
      pancreatic pseudocyst. And their tumors were not relapsed. CONCLUSIONS: There is
      an exact therapeutic effect of middle segment pancreatectomy for benign tumors of
      the amphi-neck of the pancreas. The treatment has little function damage to
      patients' endocrine and external secretion. The incidence rate of pancreatic
      fistula in middle segment pancreatectomy is higher than that in
      pancreaticoduodenectomy. As long as the drainage is kept unobstructed, most of
      the pancreatic fistula can be self cured.

PMID- 21092577
TI  - [Macrocystic serous adenoma of the pancreas: a report of 5 cases].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of macrocystic serous
      adenoma of the pancreas (MSAP). METHODS: The clinical data of 5 patients with
      MSAP treated from October 1999 to October 2009 were retrospectively analyzed.
      There were 5 female and 1 male. RESULTS: Of the 5 patients, 3 patients presented
      with abdominal pain and fullness, 1 patient with jaundice, 1 patient with
      asymptomatic. Ultrasonography and CT could manifest macrocystic lesion of the
      pancreas; all the lesion showed a well-defined border, internal septations,
      enhanced cyst walls, with no intramural (mural) nodule and papillary projections;
      the wall was smooth and thin in 4 cases; irregular lobulation could be observed
      in 3 cases, round or oval in 2 cases; 2 cases had pancreatic duct dilatation, 1
      case had biliary duct dilatation. The tumors located in the pancreatic body and
      tail in 3 cases, the tumors located the pancreatic head in 2 cases. The sizes of
      the tumors ranged from 6.5 cm to 13.0 cm (mean, 8.8 cm). Five patients all
      accepted surgical intervention. The main postoperative complication was
      pancreatic fistula (2 cases); all the fistula was cured. Recurrence or metastasis
      were not found in 5 patient followed up postoperatively from 8 to 35 months.
      CONCLUSIONS: MSAP has no specific symptoms. The imaging appearance of MSAP is
      similar to mucinous cystic neoplasm of the pancreas. The tumor can gradually grow
      up and produce compression symptoms. MSAP can be cured by complete resection.

PMID- 21092578
TI  - [The diagnosis and therapy of pancreatic cystic tumors].
AB  - OBJECTIVE: To discuss the surgical option and the treatment of complications of
      pancreatic cystic tumors. METHODS: From January 1997 to December 2009, 32
      patients with pancreatic cystic tumors in our center were reviewed
      retrospectively. There were 6 male and 26 female, aging from 24 to 76 years. Of
      the 32 patients, 16 patients had serous cystadenoma, 9 patients had mucinous
      cystadenoma; 1 patients had mucinous cystadenocarcinoma; 4 patients had
      intraductal papillary mucinous neoplasms and 3 patients had pancreatic solid
      pseudopapillary neoplasms. Tumor located in pancreatic head in 12 patients and in
      pancreatic body and tail in 20 patients. RESULTS: All patients received surgical
      treatment and there was no perioperative death. Pancreato-duodenectomy was
      performed in 10 patients, duodenum-preserving pancreatic head resection in 1
      patient, distal pancreactomy in 13 patients, including laparoscopic distal
      pancreactomy in 2 patients, pancreatic tumor resection in 3 patients, middle
      segmental resection in 4 patients; 1 patients with mucinous cystadenocarcinoma
      received palliative surgery. Complication included gastroparesis in 3 patients
      and pancreatic fistula in 5 patients, and all recovered by conservative
      treatment. These 29 patients were followed up 4 - 120 months, 3 patients died
      from tumor metastasis or other disease within 4 to 34 months after surgery.
      Others were alive and there was no tumor recurrence or metastasis. CONCLUSIONS:
      CT scan should be the first choice of non-invasive examination for cystic
      pancreatic diagnosis. Positive and timely operation should be performed in the
      patient with cystic pancreatic tumor, and it acts as a cancer preventive
      treatment. The selection of surgical approach should be individualized, the
      principal of damage control surgery should be followed. Complications such as
      gastroparesis and pancreatic fistula should be paid more attention.

PMID- 21092579
TI  - [Candidate immunogenic membrane antigens of human pancreatic cancer].
AB  - OBJECTIVE: To verify the obtained immunogenic membrane antigens candidate of
      pancreatic cancer in the performed research. METHODS: Pancreatic cancer cell line
      SW1990 membrane protein underwent immunoblot with serum IgG purified from
      clinically collected sera of 66 pancreatic cancer patients. Number 3 and number 8
      positive dots of immunoblot were identified by MALDI-TOF mass spectrometry and
      peptide mass fingerprinting matching. The candidate membrane antigens were
      further validated in cell lines by RT-PCR, real-time PCR and Western blot, and
      their different expression level of gene and protein in pancreatic cancer cell
      lines were contrastly studied. RESULTS: Number 3 and number 8 positive dots were
      identified as: voltage-dependent anion channel (VDAC3) and catechol-o
      methyltransferase (COMT). RT-PCR, real-time PCR and Western blot showed that gene
      and protein of VDAC3 and COMT were expressed in the pancreatic cancer cell line
      SW1990, AsPc and P3 respectively. CONCLUSION: VDAC3 and COMT might be the
      candidate immunogenic membrane antigens of human pancreatic cancer, and their
      gene and protein are differently expressed in the pancreatic cancer cell line
      SW1990, AsPc and P3.

PMID- 21092580
TI  - [Pentamer guided HLA-restricted epitope identification for mucoprotein 4 antigen
      of pancreatic ductal adenocarcinoma].
AB  - OBJECTIVES: To identify HLA-restricted epitope of mucoprotein 4 (MUC4) antigen as
      a tumor associated antigen of pancreatic ductal adenocarcinoma (PDAC), and to
      validate its natural presentation in PDAC patient peripheral blood. METHODS: Two
      epitope prediction databases (SYFPEITHI and ProPred-I) were used to predict HLA
      A*0201 restricted MUC4 epitope, T2 cell assay was used to determine the peptide
      binding affinity with HLA-A*0201 molecule. Dendritic cells (DCs) were induced
      from the HLA-A* 0201-positive healthy individuals' peripheral blood mononuclear
      cells (PBMC). Mature DCs were pulsed with synthesized peptides. Autologous CD8(+)
      T cells from the HLA-A* 0201 healthy donor were stimulated with the peptide
      pulsed DCs as CTL. CTL activity was assessed by lactate dehydrogenase release
      assay and IFN-gamma released by enzyme-linked immunospot assay. Pentamer was
      synthesized for HLA-A* 0201 restricted epitope P1126, then was used to detect
      specific CTL in PBMC of PDAC patients. RESULTS: Five candidate HLA-A*0201
      epitopes were predicted, LLLGVGTFV (P1125) and LLGVGTFVV (P1126) were determined
      as the two with more HLA-A*0201 affinity. Mature DCs could be induced from PBMCs.
      CTL induced by peptide P1126 could lyses T2 cells pulsed with peptide P1126 and
      HCT-116 cells [MUC4(+), HLA-A2(+)]. The number of CTL induced by peptide P1126
      which could secret IFN-gamma (130.3 +/- 6.6) was obviously higher than that in
      the negative group. By Pentamer assay, P1126-pentamer and CD8 double positive CTL
      could be detected in PBMC of PDAC patients with MUC4(+) than patients with MUC4(
      ), but no significant difference of CTL frequency between patients with HLA-A2(+)
      and with HLA-A2(-) in MUC4(+) PDAC patients. CONCLUSIONS: Tumor associated
      antigen MUC4-derived HLA-A* 0201-restrictive cytotoxic T lymphocyte (CTL) epitope
      P1126 can induce CTL reaction. The CTL can secret immunologic active material to
      induce the specific target cells lysis. P1126 epitope can be naturally presented
      in PBMC of PDAC patients, but its HLA-restriction may not be perfect.

PMID- 21092581
TI  - [Primary clinical application of traction reductor for lower limb fracture].
AB  - OBJECTIVE: To develop a traction reductor for the reduction of lower limb
      fractures during the minimally invasive surgery and explore its safety and
      efficacy. METHODS: From February 2007 to March 2009, closed or limited open
      reduction plus percutaneous plate and screw internal-fixation were conducted in
      34 patients with fracture of distal femur and tibia metaphysic, among which there
      were 3 distal femoral fractures (2 33-B, 1 33-C), 14 proximal tibial fractures (9
      41-A, 3 41-B, 2 41-C) and 17 distal tibial fractures (9 43-A, 5 43-B, 3 43-C, 2
      Gustilo I a), according to the Association for Osteosynthesis-Orthopaedic Trauma
      Association (AO-OTA) classification. Besides, closed reduction plus interlocking
      intramedullary nailing on tibial shaft fracture were applied in 36 patients (7 42
      A, 21 42-B, 8 42-C, 2 Gustilo I a). All the 70 patients, with an average age of
      37.6 years (range: 17 to 63 years) and average time before surgery of 4.7 d
      (range: 0.7 to 12.0 d), underwent reduction by self-designed traction reductor
      for lower limb fracture in the surgery. The reduction duration and C-arm
      fluoroscopy time were recorded. Recovery of the force line of affected limbs
      after surgery was determined by whether the line from anterior superior iliac
      spine to the interdigit between the first and second toe-web passed the patella
      center. And the distance from bilateral anterior superior iliac spine to medial
      malleolus tip as well as the difference between lower limbs were recorded to
      determine the recovery of length after surgery. Meanwhile, the varus-valgus and
      anteroposterior angulations after reduction were measured by AP and lateral X
      ray. RESULTS: The reduction duration was 12.7 min (range: 7 to 31 min); X-ray
      fluoroscopy time, 1.3 min (range: 0.4 to 3.0 min); length difference between both
      lower limbs (6.5 +/- 1.1) mm; and axial alignment difference (7.0 +/- 1.8) mm.
      The X-ray result showed that varus-valgus angle was (2.75 +/- 0.16) degrees ; and
      anteroposterior angulation (5.13 +/- 0.51) degrees . CONCLUSION: The traction
      reductor for lower limb fracture could achieve satisfying fracture reduction in
      the minimally invasive surgery of distal femur, tibia metaphysic and tibial shaft
      fracture.

PMID- 21092582
TI  - [Recent advances in diagnosis of flat lesions of urinary bladder].

PMID- 21092583
TI  - [Clinicopathologic and molecular genetic study of renal cell carcinoma occurring
      in teenagers].
AB  - OBJECTIVE: To investigate clinicopathological features, molecular genetic
      characteristics, differential diagnoses and prognosis of renal cell carcinoma in
      teenagers. METHODS: Microscopic and immunohistochemical features of 46 cases of
      renal cell carcinomas in teenagers were reviewed along with the clinical follow
      up data. Loss of heterozygosity (LOH), analysis of von Hippel-Lindau (VHL) gene
      and screening for VHL gene mutations were performed in all of the tumors.
      RESULTS: There were 19 Xp11.2 translocations/TFE3 gene fusions renal clear cell
      carcinomas (Xp11 RCCs), 9 chromophobe renal cell carcinomas (CCRCCs), 17
      papillary renal cell carcinomas (PRCCs), and 1 unclassified renal cell carcinoma
      (RCC). All of the 19 Xp11.2 translocation RCCs showed a moderate to strong
      immunoreactivity for TFE, however, no TFEB expression was obtained. There were 4
      histological patterns in the Xp11 RCC cases including: 8 tumors possessing a
      nested to papillary architecture resembling to the t(X;17) ASPL-TFE3 phenotype; 6
      tumors possessing a morphologic feature like the t(X;1) PRCC-TFE3 phenotype; 4
      cases morphologically resembling to clear cell RCC; and 1 Xp11 RCC case, with a
      special morphologic feature not searched yet in the literature, including a
      ground glass appearance of the nuclei accompanying occasionally with grooves on
      the nuclear surface; nucleoli inconspicuous with accumulation of abundant mucin
      like substance in the stroma. VHL gene analysis revealed deletions at 3p25-26 in
      one clear cell RCC and one papillary type 2 RCC. The papillary type 2 RCC had
      also a family history of VHL disease, with a germline G->C mutation at a splicing
      site of position 553+5. There were no VHL mutations detected in the remaining 45
      RCCs. Statistical analysis of tumor stage and outcome revealed that TFE+ RCCs of
      teen-agers were more frequently associated with a higher pT3/pT4 stage and a
      poorer outcome than that of the TFE-RCCs (P < 0.05). CONCLUSIONS: RCCs of the
      teenagers have a different morphologic spectrum and genetic background from the
      RCCs seen in adults. Among RCCs of the teen-agers, Xp11.2 translocation tumors
      are the most common RCCs and have a poorer prognosis than that of the TFE-RCCs.

PMID- 21092584
TI  - [Electron microscopic examination on 50 cases of prostatic needle biopsies].
AB  - OBJECTIVE: To study the differences in ultrastructural findings between prostatic
      carcinoma and benign prostatic hypertrophy, and the various ultrastructural
      features seen in moderately to poorly differentiated prostatic carcinoma.
      METHODS: Utrasound-guided needle biopsies were carried out in 50 clinically
      suspicious cases of prostatic carcinoma. For each case, one additional core was
      sampled from the most suspicious area, fixed in glutaraldehyde and examined under
      electron microscopy. RESULTS: In the 50 cases of prostatic needle biopsies
      studied, there were a total of 42 cases with histologic findings of prostatic
      carcinoma. Thirty-one cases showed features corresponding to Gleason's score 3 to
      5. In contrast to that seen in benign prostatic hypertrophy, the ultrastructural
      findings of the tumor cells commonly seen in prostatic carcinoma included the
      centrally located giant nucleoli, a direct contact with stroma, and formation of
      cytoplasmic microcyst. Occasionaly, there were mitotic figures seen, accompanying
      with fibromyxoid change of the peritumoural stroma. Amongst the 31 cases of
      Gleason's score 3 to 5 prostatic carcinoma, 29 cases (93.5%) demonstrated
      cytoplasmic prostasomes and storage vesicles. Similar to their counterparts in
      benign prostatic cells, prostasomes and storage vesicles in prostatic carcinoma
      cells were formed in the Golgi apparatus and released into the lumen by apocrine
      excretion and exocytosis. CONCLUSIONS: Electron microscopy is helpful in
      distinguishing between benign and malignant prostatic lesions. Because of the
      high yield of prostasomes in moderately to poorly differentiated prostatic
      carcinoma, prostasomes may become a potential target for cancer immunotherapy and
      one of the useful diagnostic indices for delineating the prostatic origin of
      metastatic carcinoma.

PMID- 21092585
TI  - [Expression of BRG1 and BRM proteins in prostatic cancer].
AB  - OBJECTIVE: To study the effect of BRG1 and BRM, the catalytic subunits expressed
      by SWI/SNF, in benign and malignant prostatic tissues and to correlate the
      BRG1/BRM expression with the development and progression of prostatic cancer.
      METHODS: The expression levels of the BRG1 and BRM proteins in benign and
      malignant prostatic tissues were studied using semi-quantitative immunohisto
      chemistry. The results correlated with various clinical and pathologic
      parameters. RESULTS: The average immuno-reactive score for BRG1 expression in
      prostatic cancer tissues was significantly higher than that in benign prostatic
      tissues (57+/-9.8 and 19+/-4.1, respectively, P = 0.000 17). The difference was
      more obvious in the high-grade cancer. On the other hand, BRM expression
      exhibited a heterogeneous pattern. The average immuno-reactive score for BRM
      expression was lower in cancer tissues than in benign tissues (112+/-17 and 151+/
      19, respectively, P = 0.0047). BRG1 and BRM demonstrated a reciprocal expression
      pattern in benign and malignant tissues. The average immuno-reactive score for
      BRG1 expression was higher in the cancer cases with a larger tumor volume than in
      the cases with a smaller tumor volume (P = 0.0112). CONCLUSIONS: The expression
      of BRG1 and BRM correlates with the development of prostatic cancer. Increased
      BRG1 expression may have certain implications in tumor progression.

PMID- 21092587
TI  - [Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma,
      with reference to the 2008 WHO classification of tumours of haematopoietic and
      lymphoid tissues].
AB  - OBJECTIVE: To study the clinical and pathologic features of 4 cases of the so
      called blastic natural killer (NK)-cell lymphoma, with reference to the 2008 WHO
      classification of tumours of haematopoietic and lymphoid tissues. METHODS: The
      clinical, pathologic and immunohistochemical findings (EliVision method) of 4
      cases of blastic NK-cell lymphoma (previously diagnosed according to the 2001 WHO
      classification) were retrospectively analyzed and reclassified with a special
      reference to the 2008 WHO classification. RESULTS: The 4 cases of hematologic
      malignancy studied were characterized by the presence of medium-sized blastic
      lymphoma cells, CD56 expression, and absence of lineage-specific B-cell, T-cell
      and myeloid cell markers. According to the 2001 WHO classification, they fell
      into the category of blastic NK-cell lymphoma. Three of the cases presented with
      primary cutaneous lesions and expression of CD56, CD4 and CD123. They are likely
      derived from the plasmacytoid dendritic cells rather than NK cells. They were
      then, according to the 2008 WHO classification, reclassified as the blastic
      plasmacytoid dendritic cell neoplasm. The remaining case showed lymph node
      involvement, positive for CD56 and CD4, negative for CD123, and not accompanied
      with the cutaneous lesions. This case was provisionally classified as a ambiguous
      lineage leukemia-NK cell lymphoblastic leukemia/lymphoma. CONCLUSIONS: The so
      called blastic NK-cell lymphomas in the 2001 WHO classification are rare and
      represent a heterogeneous group of lymphoproliferative disorders, with different
      clinical, pathologic and immunohistochemical features. It's suggested to have a
      precise category when applying the 2008 WHO classification to this kind of
      lesion.

PMID- 21092586
TI  - [Acquired somatic mutations in non-coding region of bcl-6 gene in germinal center
      type diffuse large B-cell lymphoma].
AB  - OBJECTIVE: To investigate the mutation of 5' non-coding region of bcl-6 gene in
      germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL).
      METHODS: t(14;18) detection and immunohistochemical staining (EnVision method)
      were performed in 60 cases of DLBCL, which were divided into GCB and non-GCB
      subtypes. Polymerase chain reaction (PCR), single-strand conformation
      polymorphism and direct DNA sequencing were used to identify mutations in the 5'
      non-coding region of the bcl-6 gene. RESULTS: Seven of 60 cases showed t(14;18)
      translocation in the major breakpoint region. Using minimally acceptable
      criteria, 18 of 60 cases were probably to be germinal centre derived. Bcl-6
      mutations were detected in 12 of 60 cases (20.0%) of DLBCL, with a significantly
      higher frequency in the GCB subgroups (7/18) than in the non-GCB subgroups
      (11.9%, 5/42). Bcl-6 mutations occurred most frequently in +363 and +469 sites.
      An association of bcl-6 mutation and GCB subgroup was obtained. CONCLUSIONS: The
      5' regulatory region of the bcl-6 gene underwent less frequent somatic
      hypermutation during lymphomagenesis than the results of previous reports. Bcl-6
      mutation occurred mostly in the GCB subtype and detection of t(14;18) seems
      helpful in the classification of DLBCL.

PMID- 21092588
TI  - [Detection of chromosomal DNA imbalance in medulloblastoma by comparative genomic
      hybridization].
AB  - OBJECTIVE: To investigate the relationship between chromosomal genomic DNA
      imbalance in medulloblastoma (MB), and the age and gender. METHODS: The gains and
      losses of chromosomal genomic DNA in 16 MBs were analyzed using comparative
      genomic hybridization. RESULTS: The gains and(or) losses were found in 15 of the
      16 cases. There was not significant difference (P > 0.05) between the total gains
      (10/16) and losses (11/16). Both of their differences had also no significance
      between different age and gender groups (P > 0.05). In 15 cases with gains
      and(or) losses, single-, two-, three- and multi-chromosome genomic DNA imbalances
      were 3/15, 4/15, 1/15 and 7/15 respectively. Eleven gain zones (+5q, +6q, +7q,
      +11q, +15q, +17p, +17q, +19q, +20q, +21q, +Xp) and twenty-five loss zones (-1p, 
      1q, -2p, -2q, -3q, -4p, -6p, -6q, -8p, -8q, -10p, -10q, -11p, -14q, -16p, -16q, 
      17p, -18p, -18q, -19p, -19q, -20p, -20q, -Xp, -Xq) were detected in those tumors.
      +7q (6/16), +17q (6/16), -14q (5/16) and -10q (3/16) were the most frequent, but 
      14q only occurred in the cases of > 10-year-old. CONCLUSIONS: Most MBs have
      chromosomal genomic DNA imbalances. The frequent imbalance zones are mainly at
      the long arms of some chromosomes. +7q, +17q, -14q and -10q correlate closely to
      development of the tumors. -14q is important factor to result in MBs of > 10-year
      old group. MB has possibly different molecular genetics subtype.

PMID- 21092589
TI  - [Expression of CD20 in thymomas and its clinical implication].
AB  - OBJECTIVE: To study the expression of CD20 in thymomas and its clinical
      significance. METHODS: One hundred and seventy-nine cases of thymoma were
      enrolled into the study. The histologic diagnosis was reviewed by two experienced
      pathologists on the basis of the 2004 WHO classification. One hundred and two
      cases were selected for immunohistochemical study for CD20, pancytokeratin, TdT,
      CD3, CD43, CD99 and S-100 protein. The cases were further categorized into two
      groups, according to the association with clinical evidence of myasthenia gravis.
      The immunostaining pattern was then statistically analyzed. RESULTS: Amongst the
      102 cases studied, 7 cases belonged to type A thymoma, 32 cases type AB thymoma,
      17 cases type B1 thymoma, 15 cases type B2 thymoma, 17 cases type B3 thymoma and
      14 cases thymic carcinoma. The expression rates of CD20 in neoplastic epithelial
      cells of type A, type AB, type B1, type B2 and type B3 thymomas and thymic
      carcinomas were 3/7, 84.4% (27/32), 1/17, 2/15, 0/17, 0/14, respectively. The
      proportions of CD20-positive lymphocytes in the background were 3/7, 18.8%
      (6/32), 14/17, 11/15, 11/17, 6/14, respectively. The proportion of CD20-positive
      intra-tumoral B lymphocytes in the group of thymomas with myasthenia gravis was
      67.5% (22/40), in contrast to 35.5% (22/62) in those without myasthenia gravis.
      CONCLUSIONS: The neoplastic epithelial cells in cases of type A and type AB
      thymoma, as well as few cases of type B1 and B2 thymoma, express CD20. The
      immunostain highlights the presence of oval, stellate or spindly cells. Thymomas
      associated with myasthenia gravis contain a significant population of CD20
      positive intra-tumoral B lymphocytes. Type AB thymomas may be originated from
      different populations of cells, rather than a simple admixture of type A and B
      thymoma cells.

PMID- 21092590
TI  - [Influence of phosphoprotein associated with glycosphingolipid microdomains 1 on
      biologic behavior of human prostatic cancer cell line in-vitro].
AB  - OBJECTIVE: To investigate the mechanism of influence of phosphoprotein associated
      with glycosphingolipid microdomains 1 (PAG1) on the biological behavior of human
      prostatic cancer cell line PC-3M-1E8. METHODS: The expression of GST-Raf1-RBD
      recombinant protein, a specific binding domain of active Ras (GTP-Ras), was
      induced by IPTG in JM109 bacterium. SDS-PAGE and coomassie brilliant blue
      staining were performed using cleaved product of the bacterium to determine the
      expression of the fusion protein. GST-pull down essay was designed to detect the
      level of active Ras in PGA1 and vector transfected, respectively and in the
      native PC-3M-1E8 cells. Western blotting was used to detect the expression levels
      of downstream proteins of Ras signal pathway which may be related to the function
      of PAG1. Phalloidine labeled by tetramethylrhodamine-5-(and-6) isothiocyanate
      (TRITC) was used for the staining of intracellular F-actin, Laser passing
      confocal microscopy was adopted for observing change of the cell morphology and
      the arrangement of F-actin. RESULTS: After IPTG induction, the GST-Raf1-RBD
      recombinant protein, with a molecular weight of 33 000, was noticed to be highly
      expressed in JM109 bacterium. GST-pull down assay revealed that the expression
      level of active Ras markedly decreased after PAG1-transfection while the total
      Ras remained unchanged. The expression of p-ERK and cyclin D1 in the PAG1
      transfected cells decreased in accordance with the level of active Ras. However,
      the expression of p21(WAF1/CIP1) and p-Akt didn't show any variation.
      Additionally, the structure of F-actin was turbulent and the pseudopodia of cells
      diminished conspicuously after PAG1-transfection. There was a high expression of
      PAG1 in normal human prostate tissue, however, the positive rate of PAG1 immuno
      staining decreased in cases of prostatic adenocarcinoma, correspondent with
      increasing of the grading index of cell differentiation established in the
      Gleason grading system for the diagnosis of prostate adenocarcinoma. CONCLUSIONS:
      An over-expression of PAG1 in PC-3M-1E8 cells effectively suppresses the
      activation of Ras and ERK, as well as the cyclin D1 expression, leading to an
      inhibition of the proliferation ability of tumor cells. The turbulence of F-actin
      and reduction of pseudopodia of cells result in an impairment of cell mobility,
      invasiveness and metastatic capability. In human prostate and prostatic
      adenocarcinoma tissues, the expression of PAG1 is related to the cellular
      differentiation and malignancy.

PMID- 21092592
TI  - [Calcium-binding protein secretagogin is a novel neuroendocrine marker].

PMID- 21092591
TI  - [Improved angiogenesis by P-selectin glycoprotein ligand-1 overexpression in
      endothelial progenitor cells].
AB  - OBJECTIVE: To explore whether overexpression of P-selectin glycoprotein ligand-1
      (PSGL-1) promotes the adhesive ability of endothelial progenitor cells and
      functionally facilitates neovascularization in mouse model of hindlimb ischemia.
      METHODS: Rat endothelial progenitor cells were transfected with recombinant
      adenovirus vector encoding human PSGL-1. The mRNA and protein expression levels
      of PSGL-1 were measured by RT-PCR and Western blot, respectively. The effect of
      overexpression of PSGL-1 in endothelial progenitor cells was analyzed by
      adherence assay. Histological examination of skeletal muscle sections retrieved
      from the mouse ischemic hindlimbs was performed, and the hindlimb blood flow was
      measured by laser Doppler flow meter. RESULTS: Adenovirus vector expressing of
      PSGL-1 gene was successfully constructed with high titer of 3.1 * 1011 pfu/ml.
      After transfection, PSGL-1 gene was highly expressed in the transfected
      endothelial progenitor cells. In vitro assay showed that overexpression of PSGL-1
      enhanced the adhesive properties of endothelial progenitor cells. When the
      transfected endothelial progenitor cells were transplanted into the ischemic
      hindlimb of nude mice, the number of new capillary vessels was (41.0 +/- 2.2)/HPF
      compared to that of (21.0 +/- 2.5)/HPF in the negative control group and (10.0 +/
      1.6)/HPF in the blank control group (P < 0.01). Furthermore, the blood flow was
      increased in the experimental group (119.1% +/- 7.0%), whereas in the negative
      control group, it was (93.3% +/- 3.0%) and in the blank control group it was
      (76.3% +/- 12.0%), P < 0.01. CONCLUSIONS: Overexpression of PSGL-1 enhances the
      adhesive and angiogenic properties of endothelial progenitor cells. The approach
      may provide an effective therapeutic strategy to improve the efficiency of cell
      based proangiogenic therapy.

PMID- 21092593
TI  - [Comparison of hematoxylin and eosin staining and fixation of testicular biopsies
      when using 4% formalin and Bouin's fixatives].

PMID- 21092594
TI  - [Renal Bellini's collecting duct carcinoma: report of a case].

PMID- 21092595
TI  - [Metanephric stromal tumor: report of a case].

PMID- 21092596
TI  - [Nasopharyngeal EBV-positive diffuse large B-cell lymphoma occurring in elderly:
      report of a case].

PMID- 21092598
TI  - [Chondrosarcoma of kidney: report of a case].

PMID- 21092597
TI  - [Diffuse large B-cell lymphoma following nodular lymphocyte predominant Hodgkin's
      lymphoma: report of a case].

PMID- 21092599
TI  - [Thymic carcinoid: report of a case].

PMID- 21092600
TI  - [Intrahepatic sarcomatoid cholangiocarcinoma with osteoclast-like giant cells:
      report of a case].

PMID- 21092601
TI  - [Epithelial neoplasms associated with osteoclast-like giant cells].

PMID- 21092602
TI  - [Updates of research on the relationship between SOX9 gene and human neoplasms].

PMID- 21092603
TI  - [Pay more attention to the diagnosis and treatment of parathyroid carcinoma].

PMID- 21092604
TI  - [Cytokine responses after lobectomy for early non-small cell lung cancer: a
      prospective randomized comparison of video-assisted thoracic surgery and open
      thoracotomy].
AB  - OBJECTIVE: To compare video-assisted thoracic surgery (VATS) and open thoracotomy
      (OT) on acute inflammatory responses and immunosuppression after lobectomy for
      early non-small cell lung cancer (NSCLC). METHODS: Present prospective randomized
      study. OT or VATS lobectomy was performed in patients who met enter criteria and
      clinical data was collected. Plasma concentration of IL-6, IL-8 and IL-10 were
      measured before surgery and at postoperative day (POD) 1 and POD 3. There were
      271 patients underwent lobectomy for early NSCLC, including of 133 patients in
      group VATS and 138 patients in group OT from January 2007 to June 2008. There
      were 132 males and 139 females, aging from 19 ~ 70 years with a mean of (56 +/-
      8) years. RESULTS: Compared with OT group, shorter postoperative hospital stay
      [(8.2 +/- 2.5) d vs. (9.8 +/- 6.2) d, P = 0.03], lower morbidity rate (11.3% vs.
      21.7%, P = 0.02) and lower increase of plasma concentration of IL-6 at POD 1 [(35
      +/- 25)% vs. (65 +/- 43)%, P = 0.00], IL-6 at POD 3 [(14 +/- 22)% vs. (55 +/-
      44)%, P = 0.00] and IL-10 at POD 1 [(25 +/- 20)% vs. (43 +/- 35)%, P = 0.00] were
      observed in patients of VATS group. CONCLUSION: VATS lobectomy for early NSCLC is
      associated with less acute inflammatory responses and less immunosuppression when
      compared with OT.

PMID- 21092605
TI  - [Surgical treatment results and prognostic analysis of 514 cases with
      gastroesophageal junction carcinoma].
AB  - OBJECTIVE: To clarify the important clinicopathological and therapeutical factors
      affecting the prognosis of patients with gastroesophageal junction carcinoma.
      METHODS: Data of 514 cases with gastroesophageal junction carcinoma who underwent
      surgical treatment from September 1995 to January 2007 was retrospectively
      analyzed. Relevant prognostic factors were studied with univariate and
      multivariate analysis. RESULTS: For all 514 cases (424 men and 90 women), the
      median age was 63 years. The 1-, 3- and 5-year survival rates of this group were
      74.8%, 42.1% and 29.1%, respectively. Gross type, TNM classification,
      histological type, vascular invasion and extent of surgical resection affected
      patients' survival remarkably. There was no significant difference in survival
      between operative approaches (via laparotomy or left thoracotomy) (P > 0.05).
      Long-term survival was similar between proximal subtotal gastrectomy and total
      gastrectomy in advanced cases (P > 0.05). For stage II and III tumors, patients
      with neoadjuvant chemotherapy had better prognosis than those without (P < 0.05).
      Cox multivariate regression analysis revealed TNM classification and vascular
      invasion were independent prognostic factors. CONCLUSIONS: TNM classification and
      vascular invasion are independent prognostic factors for gastroesophageal
      junction carcinoma. Neoadjuvant chemotherapy may improve prognosis of the
      patients with stage II and III tumors. Radical resection should be achieved with
      rational surgical procedures tailored by tumor position, size, staging and so on.

PMID- 21092606
TI  - [Open total extraperitoneal herniorrhaphy for inguinal hernia via a ventral
      midline incision].
AB  - OBJECTIVE: To discuss the operation skills and evaluate the effects of open total
      extraperitoneal herniorrhaphy for inguinal hernia via a ventral midline incision.
      METHODS: From June 2008 to December 2009, 106 patients with inguinal hernia
      received open total extraperitoneal herniorrhaphy via a ventral midline incision,
      the clinical data were analyzed retrospectively. RESULTS: Of the patients, 86
      cases were male, 20 were female, the mean age was 60.2 years (range, 21 - 86
      years). The mean operation time was (32.6 +/- 10.5) minutes. The postoperative
      hospital stay was (2.3 +/- 0.7) days. Intra-operative peritoneal perforation
      occurred in 2 cases. Four cases experienced urine retention and seroma happened
      in 2 cases, 6 cases suffered early surgical-site pain, and all of the
      complications were cured with conservative treatment. Three cases developed
      scrotal hydrocele. No neuralgia or incisional infection occurred in this group.
      During a 3- to 22-months follow-up period (mean, 10.2 months), no patient
      complained of discomfort or foreign body sensation in the inguinal area. Two
      cases recurred 2 and 11 months after the surgery, respectively; the recurrence
      rate was 1.9%, the two patients healed after reoperation. CONCLUSIONS: Open total
      extraperitoneal herniorrhaphy operation via a ventral midline incision is a safe,
      effective and convenient technique for inguinal hernia with few postoperative
      complications. This method is worth popularizing.

PMID- 21092607
TI  - [Total hip replacement with collum femoris preserving for the treatment of
      advanced stage of femoral head necrosis of young patients: a report of results of
      more than five years follow-up].
AB  - OBJECTIVE: To observe the results of total hip replacement with collum femoris
      preserving for the treatment of advanced stage of femoral head necrosis of youth.
      METHODS: From August 2002 to November 2009, 21 patients (28 hips) with advanced
      stage of femoral head necrosis were treated with total hip replacement with
      collum femoris preserving. Sixteen males (22 hips) and 5 females (6 hips) with an
      average age of 36 years (range from 26 to 51 years) were included. All patients
      were evaluated clinically using Harris score, the prosthesis components were
      assessed for position, loosening, bone resorption and other conditions with
      radiographs. RESULTS: Nineteen patients (26 hip) were followed up for mean 5
      years and 7 months (ranging 5 years and 3 months to 7 years and 1 month), 2
      patients were missed. The average Harris score increased from the preoperative
      average 48.5 to 90.2. The leg-length discrepancy (the difference was less than 2
      cm) occurred in 3 cases. No thigh pain and revision. CONCLUSION: Total hip
      arthroplasty with collum femoris preserving is one of the best choices for the
      treatment of advanced stage of femoral head necrosis of young patients with good
      midterm outcome.

PMID- 21092608
TI  - [Diagnosis and treatment for complicated atlantoaxial dislocation].
AB  - OBJECTIVE: To explore the clinical characteristics and treatment methods for
      complicated atlantoaxial dislocation. METHODS: A retrospective evaluation was
      done to summarize and analyze the clinical characteristics and complicated
      factors of 54 patients with complicated atlantoaxial dislocation who could not to
      be treated effectively by using conventional therapy in our hospital from
      February 2005 to October 2008. According to different complicated factors,
      different treatment methods mainly including transoral atlantoaxial reduction
      plate-III (TARP-III) operation, decompression procedure with deep grinding guided
      by computer aided design-rapid prototyping (CAD-RP), screw placement technique
      with CAD-RP guide plate and extensile approach surgery were performed. RESULTS:
      The average follow-up period was 24 months. Among 54 cases, 48 cases achieved
      immediate anatomic reduction completely and 6 cases almost achieved anatomical
      reduction. All the compressed spinal cords were decompressed sufficiently. The
      decompression rate was 86.0% and the improvement rate of nerve function was
      77.8%. Two cases suffered postoperative intracranial infection. CONCLUSION: Some
      cases of complicated atlantoaxial dislocation can be effectively treated by using
      TARP-III operation, decompression procedure with deep grinding guided by CAD-RP,
      individualized screw placement technique with CAD-RP guide plate and extensile
      approach surgery.

PMID- 21092609
TI  - [Study on the relationship between sclerosis rim and bone morphogenetic proteins
      of osteonecrosis of the femoral head].
AB  - OBJECTIVES: To analyze retrospectively the formation and histological changes of
      sclerosis rim in patients with osteonecrosis of the femoral head (ONFH), and to
      study the relationship between bone morphogenetic proteins (BMP4) and sclerosis
      rim, so as to acquire experimental and theoretical basis on individualized
      treatment for ONFH patients. METHODS: From November 2005 to November 2007, 184
      hips of steroid-induced ONFH inpatients were collected. The mean age was (47 +/-
      7) years, the patients were divided into high (more than 54 years old), middle
      (40 - 54 years old) and low (less than 40 years old) age groups. Their clinical
      data were analyzed retrospectively according to gender and age. Parts of the
      femoral heads were selected for the study, including 18 hips in high age group,
      11 hips in low age group and 20 hips in middle age group. Each 10 hips were
      selected with or without sclerosis rim. The femoral heads were cut along middle
      coronal plane, their weight-bearing and non-weight-bearing areas were used for
      the study. The specimens were processed by routine HE staining and picric acid
      Sirius red staining and electron microscopy preparation and immunohistochemistry
      stain. The average optical density of BMP4 protein was calculated by image
      analysis software. RESULTS: The trabecular of sclerosis rim was thickening and
      disorder. But its osteocytes were normal and with high secretion. The ratio of
      sclerosis rim was 71.4% (105/147) in middle age ONFH patients, which was
      significantly higher than the low age group patients (45.5%, 5/11) and high age
      group patients (38.5%, 10/26) (P < 0.01). The optical density of BMP4 in middle
      age ONFH patients was 0.32 +/- 0.14, which was significantly higher than the low
      age group 0.20 +/- 0.17 and high age patients 0.19 +/- 0.27 (P < 0.05). The
      optical density was 0.16 +/- 0.11 in ONFH patients without sclerosis rim, which
      was significantly lower than with sclerosis rim (0.28 +/- 0.13) (P < 0.01). The
      time from hip pain to joint replacement in patients with sclerosis rim was (49 +/
      11) months, and (15 +/- 2) months without sclerosis rim. There was significant
      difference between the two groups (P < 0.01). CONCLUSIONS: The formation of
      sclerosis rim is positively related to the expression of BMP4, and high
      expression of BMP maybe promote the formation of sclerosis rim.

PMID- 21092610
TI  - [Repair full-thickness meniscal defects with injectable tissue engineering
      technique].
AB  - OBJECTIVE: To investigate the effectiveness of injectable tissue engineering to
      repair full-thickness meniscal defects. METHODS: From June 2008 to February 2009
      full-thickness of meniscal defects were created in the anterior corner of goats,
      which with no blood supply, in a diameter of 2 mm. Then bone marrow stem cells
      (BMSCs) was mixed with injectable calcium alginate gel to fill the defects. Other
      groups include the calcium alginate gel and empty group were served as control
      groups. At different time points, the animals were sacrificed and macroscopy,
      microscopy determination, electroscopy and MRI detection were performed to assess
      the outcomes of repairing. RESULTS: The meniscal defects had been filled
      thoroughly in 16 weeks after operation with white, tough and elastic repair
      tissue similar to normal meniscal fibrocartilage in the tissue engineering
      groups. The repair tissue was mainly fibrochondrocytes in line with the calcium
      alginate fiber. Thick matrix secreted by the cells crammed the space between
      fibers. The view under electroscopy demonstrated that the microstructure of the
      repair tissue was normal and cells were in a fibrocartilage phenotype.
      CONCLUSION: The full-thickness meniscal defects in regions without blood supply
      can be reconstructed effectively with injectable tissue engineering.

PMID- 21092611
TI  - [The anatomic and radiographic morphometry of thoracic pedicle rib unit].
AB  - OBJECTIVES: To investigate the spatial structure of pedicle rib units in normal
      thoracic human spines and to compare the dimensions of the pedicle rib unit with
      corresponding dimensions. METHODS: Thoracic spine specimens in four fresh adult
      cadaveric were used. Computerized tomographic (CT) images (including two
      dimensional, three-dimensional reconstruction) of the thoracic spines were
      obtained. Measurement parameters include:the width, the height, the chord length
      and the sagittal angles of the pedicle rib unit compared with pedicle, especially
      for the pedicle-rib overlapping height. RESULTS: The pedicle rib unit was not a
      simple two-dimensional structure but a three-dimensional structure. The shortest
      height of pedicle rib unit was (12.6 +/- 0.8) mm (T(1)), while the longest was
      (16.9 +/- 1.1) mm (T(11)). The shortest height of pedicle-rib overlap was (7.2 +/
      0.3) mm (T(1)), while the longest was (11.8 +/- 1.0) mm (T(10)). The height of
      pedicle rib unit and the height of pedicle were significantly larger than that of
      the pedicle-rib overlap (P < 0.05), while there was no significantly difference
      between the height of pedicle rib unit and the height of pedicle (P > 0.05).
      CONCLUSIONS: The pedicle rib unit is a complicated spatial structure, and the
      longitudinal height of pedicle-rib overlap should be taken as the real height of
      the unit.

PMID- 21092612
TI  - [Unilateral pedicle screw fixation plus interbody fusion by Quadrant system
      through spatium intermuscular of multifidus].
AB  - OBJECTIVE: To explore the clinical outcome of unilateral pedicle screw fixation
      plus single cage interbody fusion through spatium intermuscular of multifidus by
      Quadrant system. METHODS: From April 2008 to April 2009, 47 patients underwent
      unilateral pedicle screw fixation plus single cage interbody fusion through
      spatium intermuscular of multifidus. There were 22 males and 25 females with the
      mean age of 58.2 years (range, 46-74 years). Among them 12 cases had far-lateral
      lumbar disc herniation, 7 cases had post-discectomy recurrence, and 28 cases had
      degenerative instability. Thirty-seven cases were treated with lumbar interbody
      fusion through transforaminal approach, 10 cases through posterior approach.
      After surgery, the radiography was carried out to demonstrate the fusion status,
      and the Nakai criterion was used for assessment. RESULTS: The average skin
      incision length was 3.2 cm (range, 3.0 to 3.5 cm), the average operative time was
      90 min (range, 70 to 160 min), and the average blood loss was 130 ml (range, 90
      to 360 ml). All cases were followed up for 8 - 20 months (average 13.6 months).
      Postoperative radiography showed no evidence of instrument failure, and 43 cases
      got bone fusion, 4 cases got suspicious fusion. At final followed-up the average
      leg pain VAS decreased from 7.4 +/- 1.1 preoperatively to 2.4 +/- 1.3
      postoperatively, the average low back pain VAS decreased from 6.7 +/- 1.3
      preoperatively to 1.8 +/- 1.5 postoperatively. According to Nakai criterion, 31
      cases were rated as excellent, 11 cases as good, and 5 cases as fair with the
      total excellent and good rate of 89.4%. CONCLUSIONS: Unilateral pedicle screw
      fixation plus single cage interbody fusion through spatium intermuscular of
      multifidus has some advantages of minimal invasiveness, less blood loss, less
      complications and reliable curative effect. It is a satisfactory lumbar fusion
      method under suitable indication.

PMID- 21092613
TI  - [Diagnosis of lower urinary tract voiding dysfunction with video-urodynamic
      studies].
AB  - OBJECTIVE: To evaluate the role of video-urodynamics (VUD) in the diagnosis of
      lower urinary tract voiding dysfunction. METHODS: From December 2008 to March
      2010, 115 patients with lower urinary tract voiding dysfunction were included in
      our study. All patients underwent VUD studies. RESULTS: Neurogenic bladder was
      found in 37 patients, including 25 male patients and 12 female patients. Among
      these patients, 18 patients were detrusor areflexia (DA), 2 patients were
      overactive bladder (OAB), 10 patients were low compliance bladder with
      hydronephrosis and 7 patients were detrusor-external sphincter dyssynergia. Non
      neurogenic voiding dysfunction was found in 59 patients, including 34 male
      patients and 25 female patients. Among these patients, bladder outlet obstruction
      was found in 33 patients, OAB in 4 patients, urethra stricture in 4 patients and
      sphincterismus in 3 patients. Seven patients receiving augmentation of bladder
      took second VUD examination, including 4 male patients and 3 female patients. One
      patient receiving Indiana pouch and one patient receiving ureter reimplantation
      all took VUD examination. Ten patients had basic normal bladder urethra function
      from VUD examination, including 6 male patients and 4 female patients.
      CONCLUSION: From combination of pressure-flow figure and real time image, VUD
      examination provides precise evidence of diagnosis and treatment for lower
      urinary tract voiding dysfunction.

PMID- 21092614
TI  - [The study of electrical acupuncture stimulation therapy combined with pelvic
      floor muscle therapy for postprostatectomy incontinence].
AB  - OBJECTIVE: To explore the effectiveness and significance of whether electrical
      acupuncture stimulation combining with pelvic floor muscle therapy (PFMT) can
      improve the recovery of urinary continence. METHODS: A total of 109 patients took
      part in the study of novel combination treatment for urinary continence from
      September 2008 to September 2009. Patients were divided into study group (n = 40)
      and control group (n = 69). The patients in study group received electrical
      acupuncture stimulation therapy combined with PFMT one week after removal the
      catheter. The patients in control group performed PFMT as the only treatment for
      post prostatectomy incontinence. The patients were followed up closely, with
      their clinical characteristics recorded, questionnaires of ICI-Q-SF filled up,
      and all the data for statistical analysis collected. RESULTS: There was a
      significant difference between the study group and the control group in the
      urinary control curve (P = 0.029). The difference of continence probability
      between these two groups became greater from 4 weeks after surgery, and the
      difference reached the peak at 6 weeks (P = 0.023). Then the difference became
      smaller, and there was no difference at 16 weeks after surgery. ICI-Q-SF
      questionnaires showed the same results. CONCLUSION: Electrical acupuncture
      stimulation therapy combining with PFMT can improve the recovery of patients'
      urinary continence after radical prostatectomy.

PMID- 21092615
TI  - [Suppression of tumor growth in renal cancer treatment with tumor vaccination
      after haploidentical bone marrow cell reconstitution].
AB  - OBJECTIVE: To investigate whether whole tumor cell vaccination strategies in
      combination with bone marrow transplantation (BMT) can stimulate graft-versus
      tumor effect (GVT). METHODS: Twenty-six BALB/c mice were randomly divided into 3
      groups: BMT group (group A, n = 10), BMT + vaccination group (group B, n = 10),
      control group (group C, n = 6). (BALB/c * C57BL/6) F1 mice [CB6F1, H-2K(b/d)]
      were used as donors. BALB/c mice of group C were only inoculated with Renca cell
      (2.6 * 10(6)). Mice of group A and B were conditioned with 8 Gy irradiation,
      followed by infusion by bone marrow cell of CB6F1 mice on day 1, then inoculated
      with Renca cell (2.6 * 10(6)) on day 8. All mice of group B were immunized
      subcutaneous on the back with 5 * 10(5) irradiated Renca tumor cells on day 9 and
      day 16. All mice of group C were inoculated with Renca cell (2.6 * 10(6)) on day
      8. In group A and B, all mice were analyzed by fluorescence activated cell sorter
      (FACS) on day 14, and 28 day after BMT. Mice were killed on day 32 after
      inoculation with tumor cell and collected blood sample. All tumors were taken out
      to be weighed and then fixed in 10% buffered formalin, embedded in paraffin, and
      cut into 5 um slices. The slices were stained with HE and examined by TdT
      mediated-dUTP nick end labeling (TUNEL). Liver, skin, intestine, and spleen were
      biopsied for histopathological examination. RESULTS: The results of chimera
      showed that engraftments of group A, B were full donor chimerism, and the
      chimerism of those remained above 90% and preserved even after 28 days. The tumor
      weight, tumor volume increment in the group B was lower than group A and C (P <
      0.05). The tumor suppressing rates of the group A and B were 54%, 60%
      respectively. The area ratio of tumor necrosis and apoptosis index (AI) of the
      tumor in the group B were higher than group A and C (P < 0.05). Graft-versus-host
      disease was not observed in each group. CONCLUSION: The mechanism of GVT after
      haploidentical allogeneic bone marrow transplantation with tumor vaccination may
      be the promotion of tumor necrosis and apoptosis.

PMID- 21092616
TI  - [Clinical outcome of single-bundle versus anatomic double-bundle reconstruction
      of the anterior cruciate ligament: a meta-analysis].
AB  - OBJECTIVE: To evaluate clinical outcome after anterior cruciate ligament (ACL)
      reconstruction with double-bundle or single-bundle by meta-analysis. METHODS:
      Randomized controlled trials (RCTs) on differences of clinical outcomes of ACL
      reconstruction were retrieved in Ovid Medline, PubMed, Embase, Cochrane Library,
      CBM and VIP database. Relevant journals or conference proceedings were also
      searched manually. Then extracted the date of KT-1000 arthrometer, pivot-shift
      testing, Lysholm score and IKDC final score in these researches. RevMan 5.0.23
      software was used for data analyses. RESULTS: Eight prospective RCTs met the
      inclusion criteria. The combined results of meta-analysis indicated that there
      was statistical difference between two operative procedures on postoperative KT
      1000 arthrometer side-to-side [WMD = -0.35, 95%CI (-0.61, -0.08), P = 0.01],
      Lysholm score [WMD = -1.91, 95%CI (-3.45, -0.37), P = 0.01]. But the difference
      of KT-1000 arthrometer side-to-side is demonstrated to be clinically
      insignificant. Others indicated that there was no statistical differences with
      respect to IKDC final score [OR = 1.80, 95%CI (0.98, 3.31), P = 0.06], having a
      normal or nearly normal pivot-shift testing [OR = 1.64, 95%CI (0.85, 3.16), P =
      0.14]. CONCLUSIONS: Double-bundle reconstruction does not result in clinically
      significant advantage when compared with single-bundle. The results do not
      support the theory that double-bundle reconstruction controls knee rotation
      better.

PMID- 21092617
TI  - [Safety needs for nano-technology promoted the development of nano-toxicology].

PMID- 21092618
TI  - [The effect of inhalable titanium dioxide on the oxidative stress among
      occupational population].
AB  - OBJECTIVE: To investigate the inhalable titanium dioxide exposure level and make
      an assessment of its oxidative effect on occupational exposed population.
      METHODS: A total of 7 workers occupationally exposing to inhalable titanium
      dioxide were recruited into the study. The basic information and occupational
      history were collected by interview, while their blood sample (10 ml for each
      subject) were collected before and after the investigation, respectively. Pre-
      and post-work shift urine samples (60 ml for each subject) were collected for 29
      days consecutively. The daily personal titanium dioxide exposure level,
      temperature and relative humidity were detected too. Urinary 8-hydroxy
      deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP)
      were detected by ELISA and latex immunoturbidimetric assay, respectively.
      RESULTS: The mean concentration of air inhalable titanium dioxide was (1.194 +/-
      1.015) mg/m(3). Serum hs-CRP level before and after the investigation was (1.13
      +/- 1.08), (1.33 +/- 1.01) mg/L, respectively. No statistical significance was
      observed between hs-CRP level before and after the investigation (t = -0.848, P =
      0.425). Pre- and post-work shift urinary 8-OHdG was (3.51 +/- 1.39), (3.65 +/-
      1.06) umol/mol Cr, respectively. A positive correlation was found between the
      concentration of inhalable titanium dioxide and the changes of 8-OHdG level (r =
      0.192, t = 2.09, P = 0.039). Linear mixed-effect models, adjusted by work shift,
      years of employment, age, body mass index, smoking status, temperature and
      relative humidity, showed no significant exposure-respond trend between the
      inhalable titanium dioxide concentration and 8-OHdG level (beta = 0.288, t =
      1.940, P = 0.055). CONCLUSION: Our findings do not support the potential link
      between occupationally exposure to inhalable titanium dioxide and high induction
      of DNA oxidative stress.

PMID- 21092619
TI  - [Effect of nano-TiO(2) intratracheal instillation on lipid metabolism of AopE
      gene-knockout mice].
AB  - OBJECTIVE: To investigate the effect of nano-TiO(2) intratracheal instillation on
      the progression of dyslipidemia and atherosclerosis in apolipoprotein E-knockout
      mice. METHODS: The nano-TiO(2) was ultrasound with phosphate-buffered saline
      solutions (PBS) into its suspension for exposure. A total of 46 specific pathogen
      free (SPF) level of 11-week-old male apolipoprotein E-knockout mice were randomly
      divided into groups by their body weights: non-treatment group (8 mice), PBS
      control group (9 mice), high dose group (1.0 mg/ml, 10 mice), medium dose group
      (0.5 mg/ml, 10 mice), and low dose group (0.1 mg/ml, 9 mice). Except the non
      treatment group, mice from other groups were intratracheally instilled with 0.05
      ml each time, twice a week. After exposure of 6 weeks, viscera index, blood TC,
      TG, HDL-C, LDL-C, and organic lipid ratio were assessed as biomarkers. Artery and
      aortic root issues were assessed by histopathology. RESULTS: After 5 weeks
      exposure, mice body weights in high dose group ((29.7 +/- 1.9) g) started to
      drop, compared to PBS control ((31.3 +/- 1.9) g, t = -1.58, P < 0.05) and low
      dose group ((31.4 +/- 1.4) g, t = -1.17, P < 0.05); after 6 weeks, high dose
      group ((28.8 +/- 1.5) g) was lower than PBS control ((30.4 +/- 1.9) g, t = -1.60,
      P < 0.05), non-treatment group ((30.2 +/- 1.3) g, t = -1.43, P < 0.05) and low
      dose group ((30.6 +/- 1.0) g, t = -1.83, P < 0.05). TC levels of non-treatment,
      PBS control, high dose group, medium dose group and low dose group were (2.92 +/-
      1.18), (3.12 +/- 0.73), (4.19 +/- 1.86), (3.46 +/- 0.72) and (2.57 +/- 0.64)
      mmol/L, respectively; TG levels were (0.39 +/- 0.13), (0.39 +/- 0.08), (0.60 +/-
      0.21), (0.55 +/- 0.19) and (0.41 +/- 0.11) mmol/L, respectively; HDL-C levels
      were (1.67 +/- 0.45), (1.54 +/- 0.67), (0.93 +/- 0.50), (1.02 +/- 0.48) and (1.31
      +/- 0.64) mmol/L; TG levels of high dose group were higher than that of non
      treatment group (t = 1.27, P = 0.03) and low dose group (t = 1.62, P = 0.01); TG
      levels of medium dose group was higher than PBS control (t = 0.16, P = 0.04), and
      TC levels of high dose group were higher than PBS control (t = 0.22, P = 0.01),
      non-treatment group (t = 0.22, P = 0.04) and low dose group (t = 0.20, P = 0.03),
      and HDL-C levels of high dose group were lower than PBS control (t = -0.61, P =
      0.04) and non-treatment group (t = -0.74, P = 0.04); organic lipid ratio of each
      group were (2.27 +/- 0.51)%, (2.06 +/- 0.53)%, (2.90 +/- 0.50)%, (2.60 +/-
      0.23)%, (2.24 +/- 0.45)%; high dose group were higher than PBS control (t = 0.85,
      P = 0.00), non-treatment group (t = 0.64, P = 0.03) and low dose group (t = 0.67,
      P = 0.01); medium dose group was higher than PBS control (t = 0.54, P = 0.02).
      The plaque lipid content and calcium content which showed the progression of
      atherosclerosis and plaque rupture were elevated in medium and high dose groups.
      CONCLUSION: Intratracheal instillation of nano-TiO(2) can induce dyslipidemia and
      accelerate the development of atherosclerosis and plaque rupture in ApoE-/-mice.

PMID- 21092620
TI  - [Cell toxicity assessment methodologies applied in the study of the toxicity of
      nano-alumina to nerve cells].
AB  - OBJECTIVE: To observe the effect of nano-alumina on nerve cell viability through
      different detection kits of cell viability, using micro-alumina and nano-carbon
      as controls. METHODS: Primary culturing nerve cells of mouse in vitro, which were
      exposed to 7 doses of 0 umol/L, 62.5 umol/L, 125.0 umol/L, 250.0 umol/L, 500.0
      umol/L, 1.0 mmol/L, 2.0 mmol/L concentrations of nano-alumina (nano-Al), micro
      alumina (micro-Al) and nano-carbon (nano-C), detecting cell viability (A(570)
      values) with CCK-8, MTT and LDH methods. RESULTS: (1) The results of CCK-8 kit
      showed that, in doses of 250.0 umol/L - 2.0 mmol/L, the cell viability values of
      nano-alumina (the values of A(570) were 0.878 +/- 0.009, 0.823 +/- 0.016, 0.647
      +/- 0.008, 0.594 +/- 0.013, respectively) were significantly lower than that of
      micro-Al (the values of A(570) were 0.960 +/- 0.008, 0.951 +/- 0.036, 0.833 +/-
      0.008, 0.708 +/- 0.012, respectively) and nano-C (the values of A(570) were 0.977
      +/- 0.003, 0.973 +/- 0.002, 0.924 +/- 0.006, 0.891 +/- 0.023, respectively).
      While, comparing nano-Al with the same dose of micro-Al, there was significant
      difference (the t values were -0.082, -0.128, -0.186, -0.114, respectively, P <
      0.01), and so as to the comparison of nano-Al with the same dose of nano-C (the t
      values were -0.099, -0.150, -0.277, -0.297, respectively, P < 0.01). (2) MTT
      results showed that in the doses of 500.0 umol/L and 1.0 mmol/L, the cell
      viability of nano-Al (the values of A(570) were 0.648 +/- 0.095 and 0.575 +/-
      0.061) were lower than that of micro-Al (the values of A(570) were 0.830 +/-
      0.044 and 0.816 +/- 0.014) and nano-C (the values of A(570) were 0.889 +/- 0.009
      and 0.765 +/- 0.049), and the differences were significant (nano-Al compared with
      the same dose of micro-Al, the t values were -0.183 and -0.242, P < 0.01; nano-Al
      compared with the same dose of nano-C, the t values were -0.241 and -0.190, P <
      0.01). (3) LDH results showed that in the dose from 125.0 umol/L to 2.0 mmol/L,
      the LDH release of nano-Al group (the values of A(570) were 1.862 +/- 0.102,
      1.905 +/- 0.066, 1.930 +/- 0.037, 1.946 +/- 0.033, 1.967 +/- 0.068, respectively)
      were higher than that of nano-C (the values of A(570) were 1.484 +/- 0.110, 1.559
      +/- 0.039, 1.663 +/- 0.014, 1.732 +/- 0.076, 1.765 +/- 0.073, respectively), and
      the differences were significant (the t values were -0.377, 0.346, 0.266, 0.213,
      0.202, respectively, P < 0.01). In the dose from 125.0 umol/L to 1.0 mmol/L, the
      LDH release of nano-Al group were higher than that of micro-Al (the values of
      A(570) were 1.578 +/- 0.011, 1.639 +/- 0.025, 1.727 +/- 0.024, 1.808 +/- 0.020,
      respectively), and the differences were significant (the t values were 0.284,
      0.266, 0.202, 0.172, respectively, P < 0.01). CONCLUSION: The toxicity of nano-Al
      is greater than nano-C and micro-Al on the viability of nerve cells; LDH is more
      suitable for detecting changes of cell viability after the effect of nano
      materials than CCK-8 and MTT.

PMID- 21092621
TI  - [Cytotoxicity and its mechanism of zinc oxide nanoparticles on human leukemic
      monocyte lymphoma cell line U937].
AB  - OBJECTIVE: To investigate the cytotoxicity and its mechanism of ZnO nanoparticles
      on human leukemic monocyte lymphoma cell line U937. METHODS: Four different size
      ZnO (10, 30, 60, 500 nm) were carefully characterized. The survival rate and
      viability were measured by trypan blue assay and MTT assay for each size ZnO
      particles at different concentrations (12, 120, 240, 600, 1200 umol/L). The zinc
      probe, Fluozin-3, was used to detect the intracellular free zinc. Transmission
      electron microscopy was adopted to observe the cellular ultrastructure and the
      uptake of ZnO. RESULTS: All four kinds of ZnO were rod shape, with a purity of >
      99.9 wt%, and they were classified as zincite phase crystal and their surface
      areas were in accordance with the sizes. The viability (ZnO-n10: (97 +/- 19)%,
      (91 +/- 4)%, (24 +/- 4)%, (15 +/- 2)%; ZnO-n30: (111 +/- 4)%, (81 +/- 3)%, (24 +/
      2)%, (27 +/- 8)%; ZnO-n60: (105 +/- 11)%, (73 +/- 20)%, (43 +/- 11)%, (28 +/-
      14)%; ZnO-um: (88 +/- 16)%, (62 +/- 7)%, (22 +/- 4)%, (13 +/- 5)%) of cells
      exposed to ZnO decreased with the increasing of the concentration of ZnO from 12
      to 600 umol/L (r values were 0.965, 0.979, 0.998, 0.992, and the t values were
      19.8, 25.3, 76.3, 40.9, respectively, P < 0.05). The liability (ZnO-n10: (98 +/-
      1)%, (67 +/- 2)%, (59 +/- 7)%, (13 +/- 13)%, (5 +/- 4)%; ZnO-n30: (98 +/- 1)%,
      (97 +/- 2)%, (50 +/- 3)%, (20 +/- 14)%, (7 +/- 2)%; ZnO-n60: (97 +/- 2)%, (88 +/-
      5)%, (48 +/- 10)%, (12 +/- 5)%, (4 +/- 1)%; ZnO-um: (96 +/- 1)%, (76 +/- 3)%, (58
      +/- 3)%, (19 +/- 5)%, (20 +/- 10)%) of cells exposed to ZnO decreased with the
      increasing of the concentration of ZnO from 12 to 600 umol/L (r valued at 0.982,
      0.956, 0.972, 0.980, and the t valued at 19.3, 12.1, 15.6, 18.5, respectively, P
      < 0.05). The increase of the zinc concentration showed by the zinc fluorescence
      probe was 121 +/- 11, which was similar to the fluorescence of cells treated with
      ZnAc(2) (132 +/- 14, F = 0.6, P > 0.05) at the Zn-equivalent concentration. There
      was no statistic difference for the percents of high zinc content cells in total
      cells exposed to ZnO-n30 (87.6 +/- 2.6)% and these exposed to ZnAc(2) (86.9 +/-
      3.2)% (F = 1.5, P > 0.05). CONCLUSION: ZnO nanoparticles are highly cytotoxic to
      U937 cells and the solubilization of ZnO is the main toxicological mechanism.

PMID- 21092622
TI  - [Comparative study of the pulmonary function equipment and Douglas-bag in the
      energy consumption measurement of Chinese healthy youth].
AB  - OBJECTIVE: To determine the validity of the pulmonary function equipment.
      METHODS: 12 young students (including six males and six females) were enrolled as
      our research subjects. And the values of oxygen consumption (VO(2)), carbon
      dioxide production (VCO(2)) and energy expenditures (EE) of the subjects under
      three typical activity intensities: resting, moderate intensity (on a treadmill
      with grade 10% and speed 2.7 km/h) and hard intensity (on a treadmill with grade
      10% and speed 5.8 km/h) were measured using the pulmonary function equipment
      (K4b(2)) and Douglas-bag respectively. And the Douglas-bag method was used as
      reference and the results were compared with the other method. RESULTS: The
      measured VO(2) values by using the Douglas-bag and the pulmonary function
      equipment under three typical activity intensities were: at rest (0.22 +/- 0.03),
      (0.22 +/- 0.05) L/min (t = 0.120, P > 0.05); moderate intensity condition (0.95
      +/- 0.12), (0.96 +/- 0.14) L/min (t = 0.240, P > 0.05); hard intensity condition
      (1.63 +/- 0.28), (1.54 +/- 0.35) L/min (t = 1.487, P > 0.05). For VCO(2) values:
      at rest (0.18 +/- 0.02), (0.18 +/- 0.04) L/min (t = 0.425, P > 0.05); moderate
      intensity (0.82 +/- 0.11), (0.83 +/- 0.13) L/min (t = 0.579, P > 0.05); hard
      intensity (1.64 +/- 0.27), (1.52 +/- 0.39) L/min (t = 2.330, P < 0.05). And for
      EE values, at rest (269.40 +/- 35.70), (267.02 +/- 55.39) kJ/h (t = 0.200, P >
      0.05); moderate intensity (1165.76 +/- 148.06), (1185.91 +/- 161.89) kJ/h (t =
      0.326, P > 0.05); hard intensity (2062.91 +/- 341.97), (1912.27 +/- 483.88) kJ/h
      (t = 1.718, P > 0.05) respectively. The results showed that there were no
      significant differences between the two methods except the VCO(2) values under
      high intensity condition was underestimated by the pulmonary function equipment.
      Bland-Altman test showed that the difference of the two methods was evenly
      distributed by the mean and standard error of the system was 24.7 kJ/h. Our data
      showed the results from the Douglas-bag and the pulmonary function equipment were
      consistent. CONCLUSION: Pulmonary function equipment had good validity in
      assessing the energy expenditure in Chinese adults.

PMID- 21092623
TI  - [Association of aldosterone synthase (CYP11B2) gene -344T/C polymorphism with
      essential hypertension in Mongolian nationality].
AB  - OBJECTIVE: To explore the relationship between the -344T/C polymorphism of
      aldosterone synthase (CYP11B2) gene and essential hypertension in Chinese
      Mongolian population. METHODS: By cluster-sampling method, a total of 1575
      Mongolian people in Tongliao city of Inner Mongolia were included in this study.
      And 417 subjects were normotension, 596 subjects were prehypertension and 562
      subjects were essential hypertension. A survey was conducted to collect data by
      personal interview using a standard questionnaire, meanwhile fasting blood
      samples were drawn. Height, weight, waist circumference, blood pressure, blood
      fat indexes and fasting plasma glucose were measured. The variant genotypes of
      CYP11B2 were identified by PCR assays. The relationship between the -344T/C
      polymorphism of CYP11B2 gene and essential hypertension were analyzed by
      multinomial logistic regression model. RESULTS: Crude prevalence of
      prehypertension among Mongolian people was 37.84% (596/1575) and hypertension was
      35.68% (562/1575). The age-standardized prevalence of prehypertension was 38.57%
      and hypertension was 31.53%. The frequency of the T and C allele was 0.66
      (481/728) and 0.34 (247/728) for normotension group, 0.69 (696/1042) and 0.33
      (346/1042) for prehypertension group, 0.71 (706/998) and 0.29 (292/998) for
      hypertension group. The multiple logistic models showed CYP11B2 variant genotypes
      were associated with prehypertension (TT/CC, OR = 1.33, 95%CI: 0.87 - 2.01;
      TC/CC, OR = 1.74, 95%CI: 1.13 - 2.67; TC + TT/CC, OR = 1.49, 95%CI: 1.01 - 2.22);
      CYP11B2 variant genotypes were associated with hypertension (TT/CC, OR = 1.70,
      95%CI: 1.07 - 2.70; TC/CC, OR = 1.59, 95%CI: 0.98 - 2.50; TC + TT/CC, OR = 1.66,
      95%CI: 1.06 - 2.58). CONCLUSION: CYP11B2 gene -344T/C polymorphism were
      associated with essential hypertension in Chinese Mongolian population.

PMID- 21092624
TI  - [A survey of Japanese encephalitis antibody migrant workers in Shenzhen 2009].
AB  - OBJECTIVE: To understand the immunological status of Japanese encephalitis (JE)
      antibodies amongst migrant workers and to provide epidemiological basis for
      public health strategies on JE prevention and control in Shenzhen. METHODS: A
      multi-stage random sampling method was used, and 1003 migrant workers aged 18 to
      60 from 44 factories were investigated and their serum specimens were collected.
      The enzyme-linked immunosorbent assay (ELISA) was used to detect JE antibodies
      qualitatively. RESULTS: The gross IgG seroprevalence rate for JE was 20.2%
      (203/1003). Sex-specified seroprevalence was 21.2% (103/485) for male and 19.3%
      (100/518) for female, respectively (chi(2) = 579, P > 0.05). Age-specific
      seropositive rates were 22.6% (12/53) for those below 20 years old, 18.7%
      (120/642) for those between 20-years old, 26.0% (58/223) for those between 30
      years old and 15.3% (13/85) for those on or above 40 years old (chi(2) = 7.96, P
      > 0.05). Proportions for self-reported positive immunization, non-immunization
      and unclear immunization history were 22.1% (30/136), 22.1% (51/231) and 19.2%
      (122/636), respectively (chi(2) = 501, P > 0.05). Seroprevalence by region of
      origins showed that workers from Guangdong province was the highest (30.5%,
      50/164), followed by workers from Guangxi (29.7%, 22/74) whilst workers from
      Shan(3)xi (5.4%, 2/37) had the lowest rate. Seroprevalence rate for managers
      (29.0%, 31/107) was higher than that of technicians (7.1%, 1/14) (chi(2) = 21.78,
      P < 0.05). Serological positive rate of workers with university or above
      educational background was the highest (32.7%, 16/49), followed by that for
      individuals with college degree (10.3%, 10/97) (chi(2) = 13.02, P < 0.05).
      CONCLUSION: No associations are detected between JE seroprevalence and age, or
      sex, or self-reported immunization histories amongst migrant labor workers in
      Shenzhen. However, correlations between JE serological positive rate and region
      of origins, occupation and educational attainment are found to be significant.
      The gross seroprevalence of JE antibodies suggests that the level of JE
      antibodies amongst Shenzhen migrant workers is low and the population immunity
      barrier has yet to be established. It is necessary to strengthen prevention and
      control strategies of JE among labor workers of Shenzhen.

PMID- 21092625
TI  - [Multilocus sequence typing and pulsed-field gel electrophoresis analysis of
      Salmonella Paratyphi A isolates from 2000 to 2008, China].
AB  - OBJECTIVE: To analyze molecular and evolution characteristics of Salmonella
      Paratyphi A isolates from 2000 to 2008, China. METHODS: Using pulsed-field gel
      electrophoresis (PFGE) method with SpeI restriction enzyme, and multilocus
      sequence typing (MLST) method based on housekeeping genes (aroC, thrA, hisD,
      purE, sucA, dnaN, hemD, adk, and purA), the genomic variations of 118 Salmonella
      Paratyphi A isolates from 10 regions during 2000 to 2008 were analyzed. RESULTS:
      Using PFGE method, 118 Salmonella Paratyphi A isolates were clustered into 32
      PFGE patterns, and 5 patterns were predominant (5 isolates or above). However,
      only 2 MLST types were identified for all isolates with MLST method. Among all
      Salmonella Paratyphi A isolates, the sequences of housekeeping genes were highly
      conservative and showed a high degree of cloning. CONCLUSION: For Chinese
      epidemic Salmonella Paratyphi A isolates during 2000 - 2008, MLST method showed
      low discrimination power and the MLST method should not be applied to outbreak
      and epidemiological surveillance of Salmonella Paratyphi A. Currently, nationwide
      paratyphoid fever epidemics is caused by highly clonal isolates in China. As the
      time changes, these isolates also accumulate sporadic mutations.

PMID- 21092626
TI  - [Mechanism study of adaptive response in high background radiation area of
      Yangjiang in China].
AB  - OBJECTIVE: To study the adaptive response mechanisms in high background radiation
      area (HBRA) among Yangjiang local people through gene and protein expression of
      receptor for advanced glycation end products (RAGE) and S100A6 in peripheral
      blood and sputum in inhabitants of HBRA. METHODS: A total of 53 male inhabitants
      were selected from HBRA in Yangjiang as the exposure group, while 53 male
      inhabitants were selected from Enping (control area, CA)as the control group. The
      content of RAGE and S100A6 gene and protein were detected by RT-PCR and Western
      blotting assay. Thermo luminescent dosemeter(TLD) assay was used to measure the
      outside dose and estimate the effective dose. RESULTS: The effective dose in CA
      and HBRA was respectively 1.95 mSv and 6.24 mSv, which was 3 fold difference.
      Compared with CA, RAGE and S100A6 expression were significantly reduced in both
      gene and protein level in HBRA. The relative median mRNA expression of RAGE and
      S100A6 in peripheral blood were respectively 0.28, 1.06 and 0.16, 0.79 in CA and
      HBRA group, there was significance (with analysis Z values of -2.587 and -2.328
      respectively, P < 0.05) with Wilcoxon rank test. For the protein of sputum, the
      relative median expression were respectively 2.98, 2.25 and 0.53, 0.47 with
      significant difference (with analysis Z values of -2.201 and -2.366 respectively,
      P < 0.05) by Wilcoxon rank test. CONCLUSION: The low expression of RAGE and
      S100A6 in HBRA group might be correlated with the adaptive response and the low
      mortality of cancer in HBRA.

PMID- 21092628
TI  - [Role of endobronchial ultrasound-guided transbronchial needle aspiration in the
      respiratory diseases].

PMID- 21092627
TI  - [Associations of polymorphisms of methionine synthase A2756G and methionine
      synthase reductase G66A with the risks of coronary artery disease: a meta
      analysis].
AB  - OBJECTIVE: To evaluate the associations between polymorphisms of methionine
      synthase(MTR) A2756G and methionine synthase reductase(MTRR) G66A and risk of
      coronary artery disease. METHODS: Literatures in Medline reporting the
      relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of
      coronary artery disease from January 1990 to May 2010 were searched. A total of
      14 relevant articles were selected and 13 of them met the criteria. A Meta
      analysis was performed to estimate the pooled odds ratio (OR) to evaluate the
      relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of
      coronary artery disease. All analyses were performed using the STATA statistical
      software. RESULTS: Among the 13 studies, eight case-control studies containing
      2143 cases of coronary artery disease and 2270 controls were included in the
      analysis of MTR A2756G and risk of coronary artery disease. Meanwhile, five case
      control studies with 811 cases of coronary artery disease and 387 controls were
      included in the analysis of MTRR G66A and risk of coronary artery disease. In the
      analysis of MTRR G66A related to the risk of coronary artery disease, there were
      246 GG carries, 397 AG carriers and 168 AA carriers in the group of coronary
      artery disease, against 102 GG carriers, 203 AG carriers and 82 AA carriers in
      the control group. Compared with the MTRR GG carriers, the risk of coronary
      artery disease decreased significantly by 27% (OR = 0.73, 95%CI: 0.54 - 0.99) and
      25% (OR = 0.75, 95%CI: 0.56 - 1.00) (Egger's test t = -0.19, P = 0.862) in the
      MTRR 66 AG and AG/AA carriers, respectively, and also decreased in the MTRR AA
      carriers but significant difference was observed (OR = 0.84, 95%CI: 0.42 - 1.68).
      There was no significant association between coronary artery disease and MTR
      A2756G. CONCLUSION: These results suggest that MTRR66 may play a role in coronary
      artery disease susceptibility. MTRR 66 A allele carries are associated with a
      statistically significant decreased risk of coronary artery disease
      susceptibility.

PMID- 21092629
TI  - [Atypical pathogens in adult patients admitted with community-acquired
      pneumonia].
AB  - OBJECTIVE: To investigate the current status of atypical pathogen associated
      infections in community-acquired pneumonia (CAP) in adults, and their clinical
      attributes. METHODS: Clinical data, sputum specimens from acute phase, and paired
      sera from acute- and convalescent-phases of CAP in 153 adult patients were
      collected from May 2005 to May 2008 in multiple medical centers. Chlamydia
      pneumoniae (Cpn) IgG antibody, and Legionella pneumophila (LP) mixed IgG, IgA and
      IgM antibodies were determined by indirect immuno-fluorescent assay. Mycoplasma
      pneumoniae (Mpn) mixed IgG, IgA and IgM antibodies were determined by passive
      agglutination assay. All the sputum specimens were routinely cultured for
      bacterial isolation. RESULTS: Fifty-two (34%) out of the 153 cases were diagnosed
      as atypical CAP per the paired serum-antibody assay. Forty-seven of the 52
      atypical CAP cases were infected by one atypical pathogen, 38 with Cpn, 4 with
      Mpn, and 5 with LP, while 5 out of the 52 atypical CAP cases were infected by 2
      pathogens, Cpn and Mpnin 2, Cpn and LP in 3 cases. Eleven cases (21.2%) out of
      the 52 patients with atypical pneumonia were complicated with bacterial
      infection. Except peripheral white blood count was significant increased in the
      group of typical (bacterial only) pneumonia (WBC > 10 * 109)/L, P = 0.03), all
      the other clinical parameters did not show statistically significant difference
      between the typical and the atypical pneumonia groups. CONCLUSIONS: Our data
      suggest that Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella
      pneumophila are common pathogens of adult CAP. Chlamydia pneumoniae might be the
      most frequent atypical pathogen associated with atypical CAP.

PMID- 21092630
TI  - [Clinical analysis of 26 cases of nocardiosis].
AB  - OBJECTIVE: To describe the clinical characteristics of nocardiosis. METHOD: The
      clinical and radiological data of 26 patients with nocardiosis admitted into
      Peking Union Medical College Hospital from 1st January 1990 to 1st January 2010
      were retrospectively analyzed. All of the patients had our microbiology
      laboratory identified nocardia species in one or more clinical specimens.
      RESULTS: Nocardiosis was diagnosed in 10 men, aged from 29 to 80 years, mean (52
      +/- 14) years, and in 16 women, aged from 15 to 71 years, mean (42 +/- 17) years.
      No cases were identified in children. Six patients had no significant underlying
      conditions, while the other patients had at least one underlying condition,
      including autoimmune diseases (n = 6), chronic lung disease (n = 6), neoplastic
      disease (n = 2), chronic renal disease (n = 3), diabetes mellitus (n = 1), chest
      crush injuries (n = 1) and Cushing's syndrome (n = 1). Eleven cases had been
      receiving corticosteroids. The most common manifestations were moderate to high
      fever (n = 25), cough (n = 22), expectoration (n = 19), pleuritic chest pain (n =
      10), hemoptysis (n = 8) and moist rales (n = 10). Some of them had subcutaneous
      (n = 5) and brain abscess (n = 4). Blood tests showed elevated ESR in 14 cases
      and decreased albumin levels in 14 cases. Patchy infiltrates or consolidation (n
      = 21) and cavitations (n = 10) were the main manifestations of chest radiology.
      Pleural effusions (n = 13) were common complicated manifestations. Thoracic
      lesions were always bilateral (n = 15). Only 4 patients were diagnosed by sputum
      culture. The other patients were diagnosed by culture of specimens obtained
      invasively: 8 positive pleural effusions, 2 positive bronchioalveolar lavage
      culture, 1 positive bronchial washings, 4 positive abscesses, 7 positive lung
      tissues, and 1 positive brain abscess. Nocardia brasiliensis (n = 9) and Nocardia
      asteroids (n = 6) were the main species. There was one case with Nocardia
      otitisdiscaviarium infection and the other cases with Nocardia undifferentiated.
      Result of antimicrobial susceptibility was unavailable in 10 cases. Among the
      other 16 results, 7 strains of nocardia were resistant to trimethoprim
      sulfamethoxazole (TMP(CO)). Six cases were treated with a single drug, 5 cases
      with trimethoprim-sulfamethoxazole and 1 with minocycline. The other patients
      were given combination treatment, including trimethoprim-sulfamethoxazole,
      amikacin, cefuroxime, ceftriaxone, amoxicillin-clavulanic acid, streptomycin,
      evofloxacin, ciprofloxacin, minocycline and imipenem. Four patients died, 2
      patients relapsed and the other 20 cases cured. CONCLUSIONS: For immunosuppressed
      patients, nocardia infections should be considered when they had moderate to high
      fever and respiratory manifestations, especially accompanied with subcutaneous
      and/or brain abscess, and the chest radiology showed patchy infiltrates and/or
      consolidations. Further specific microbiological studies and sufficient therapy
      should be obtained as quickly as possible.

PMID- 21092631
TI  - [Antimicrobial resistance and genotyping of Acinetobacter baumannii in ICU].
AB  - OBJECTIVE: To investigate the outbreak of acinetobacter baumannii in the ICU, and
      to explore the antimicrobial resistance characteristics of pathogens, and
      therefore to determine the optimal prevention strategies. METHODS: From May to
      June 2007, most of the cases of infection by acinetobacter baumannii in our ICU
      were collected. PFGE (pulsed field gel electrophoresis) and standard disk
      diffusion susceptibility tests were performed on the strains isolated from the
      patients' body fluids including sputum, blood, urine, secretion and from the ICU
      environment involving the patients' bed sheet, skin surface and medical staff's
      hands, humidification water of ventilator tubes. RESULTS: Twelve strains were
      resistant to imipenem and meropenem. Colistin sulphate and tigecycline showed a
      high rate of antimicrobial activity against the strains, the rate of
      susceptibility being 100% and 91.7% respectively. These strains belonged to 3
      clones (clone A, B, C) and there were 2 sub-clones (A1, A2) belonging to clone A.
      The sub-clone A1 was isolated from the surface of unwashed medical staff's hands
      and patients' body fluids. From intermediate to resistance, the antimicrobial
      characteristics of clone A and clone B to minocycline changed over a month, and
      there was one strain that was resistant to tigecycline. CONCLUSION: The outbreak
      of acinetobacter baumannii in the ICU was caused by carbapenem resistant
      acinetobacter baumannii (CRAb). The delicate changes of disk diffusion
      susceptibility in clones A and B occurred in one month. Unwashed hands of medical
      staff were probably responsible for the outbreak.

PMID- 21092632
TI  - [Multiple serum antigenic assays for diagnosis of invasive fungal infections in
      non-neutropenic adult patients].
AB  - OBJECTIVE: To evaluate the value of plasma 1, 3-beta-D-glucan (G), serum mannan,
      galactomannan (GM) and cryptococcus capsular antigen assays for diagnosis of
      invasive fungal infections (IFI) in non-neutropenic adult patients. METHODS: This
      was a prospective case control study. Plasma and serum samples from 25 patients
      with IFI (candidiasis, aspergillosis, cryptococcosis, zygomycosis, pneumocystis
      carinii pneumonia), 27 patients with bacterial infections, and 25 healthy adults
      were collected from February 2007 to February 2009 in Beijing Hospital. The serum
      antigenic assays were performed and their sensitivity and specificity were
      analyzed. Optimal cut-off level of G test and mannan was established with
      receiver operating characteristic curve (ROC). RESULTS: The concentration of G
      test in plasma of patients with IFI [89.4 (25.8, 336.9) ng/L] was significantly
      higher than that of patients with bacterial infection [8.1 (5.0, 34.9) ng/L, U =
      120.5, P < 0.001] and healthy adults [3.8 (3.8, 26.0) ng/L, U = 76.5, P < 0.001].
      The area under curve (AUC) was 0.858, and the optimal cut-off value was 71.7
      ng/L. The sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) were 65.0% (13/20), 92.3% (48/52), 76.5% (13/17) and 87.2%
      (48/55) respectively. The concentration of mannan in serum from patients with
      candidiasis [1.13 (0.44, 1.22) ug/L] was significantly higher than that from
      patients with non-candidiasis IFI [0.21 (0.14, 0.27) ug/L, U = 19, P < 0.05],
      bacterial infection [0.26 (0.22, 0.32) ug/L, U = 36.5, P < 0.001] and healthy
      adults [0.25 (0.22, 0.30) ug/L, U = 29.5, P < 0.001]. The AUC was 0.894, and the
      optimal cut-off value was 0.41 ug/L. The sensitivity, specificity, PPV and NPV
      were 83.3% (10/12), 90.4% (47/52), 66.7% (10/15) and 96.0% (47/49) respectively.
      The sensitivity, specificity, PPV and NPV of GM antigen to diagnose aspergillosis
      were 25.0% (1/4), 96.1% (50/52), 33.3% (1/3) and 92.6% (50/54) respectively. The
      sensitivity, specificity, PPV and NPV of cryptococcus capsular antigen to
      diagnose cryptococcosis were all 100%. CONCLUSIONS: 1,3-beta-D-glucan, mannan and
      cryptococcus capsular antigen were useful for diagnosis of IFI in non-neutropenic
      adult patients. GM antigen did not show a good sensitivity for diagnosis of
      aspergillosis in non-neutropenic adult patients.

PMID- 21092633
TI  - [Cytochrome C oxidase expression and endothelial cell apoptosis in lungs of
      patients with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To observe the expression and activity of cytochrome C oxidase and
      pulmonary endothelial apoptosis in lungs of COPD patients, and therefore to
      investigate the pathogenesis of COPD. METHODS: According to COPD diagnostic
      criteria and patients' smoking status, 20 patients who had undergone lung
      resections were divided into 3 groups: group A, non-smokers without COPD (7
      patients); group B, smokers without COPD (7 patients); and group C, smokers with
      COPD (6 patients). Their normal lung tissues were used in the study. TUNEL assay
      was used to assess pulmonary vascular endothelial apoptosis. Cytochrome C oxidase
      (COX) activity was measured by spectrophotometry. Semi-quantitative polymerase
      chain reaction and Western blot were used to measure COX subunit II (COXII) mRNA
      and protein expression respectively. Moreover, immunohistochemistry was used to
      detect COXII protein expression in pulmonary endothelial cells. One-way ANOVA and
      LSD-t test were used for statistics. RESULTS: The apoptotic index of pulmonary
      vascular endothelial cells in group C [(13.8 +/- 1.9)%] was significantly higher
      than that in group B [(9.6 +/- 0.8)%] and group A [(5.9 +/- 1.0)%]. While COX
      activity and COXII mRNA expression of lung tissues and COXII protein expression
      of pulmonary endothelial cells in group C [(4.4 +/- 0.7) * 105 U/kg, (0.76 +/-
      0.17) and (14.5 +/- 1.6), respectively] were significantly lower than those in
      group A [(7.6 +/- 0.4) * 105 U/kg, 0.86 +/- 0.20 and 23.8 +/- 3.4, respectively]
      and group B [(6.0 +/- 0.6) * 105 U/kg, 0.81 +/- 0.15 and 18.6 +/- 2.1,
      respectively] (t = -13.66 - 13.27, all P < 0.05). The correlation analyses showed
      that COX activity was correlated positively with FEV1 % pred and FEV1/FVC (r =
      0.84, 0.91, all P < 0.01), but negatively with smoking index (r = -0.78, P <
      0.01). The apoptotic index of pulmonary vascular endothelial cells was negatively
      correlated with COXII expression (r = -0.75, P < 0.01). CONCLUSIONS: Increased
      pulmonary vascular endothelial apoptosis and decreased COX expression and
      activity, which were often associated with cigarette smoking, were present in
      COPD patients. COX might mediate the pulmonary vascular endothelial apoptosis in
      COPD.

PMID- 21092634
TI  - [Analysis of the electrocardiographic findings in 288 patients with acute
      pulmonary thromboembolism].
AB  - OBJECTIVE: To research variety orderliness of electrocardiogram in patients with
      acute pulmonary thromboembolism (PET). METHOD: 288 patients with first episode of
      acute PET were included in the study: There were 136 patients with massive and
      sub massive PTE (group A) and 152 with non-massive PET (group B). Thrombolytic
      agents were used for patients in group A and anticoagulant agents for those in
      group B. The electrocardiographic patterns of these patients were observed on 6
      time points during the course. The rate of electrocardiographic abnormalities and
      differences between groups were analyzed. RESULT: A high rate of S(I)Q(III)T(III)
      change was observed, 32.4% (44/136) in group A and 21.7% (33/152) in group B.
      Q(III), T(III), and S(I)T(III) were also very common. Negative T-waves in
      precordial leads were present in 77.8% (105/136) of patients in group A, and
      52.0% (79/152) in group B. The amplitude of R(aVR) and S(V5) was decreased
      gradually and regularly after treatment. The highest rate of left axis deviation
      was 47.06% in group A and 30.26% in group B, the difference being significant
      between the 2 groups. The occurrence of right axis deviation was lower, 16.2%
      (22/136) in group A and 15.1% (23/152) in group B, with no significant
      difference. CONCLUSION: The electrocardiographic findings were useful in the
      early diagnosis of PTE.

PMID- 21092635
TI  - [A study on the activity of clofazimine with antituberculous drugs against
      Mycobacterium tuberculosis].
AB  - OBJECTIVE: To explore the role of clofazimine in combination with other
      antituberculous drugs against Mycobacterium tuberculosis. METHODS: The minimal
      inhibitory concentration (MIC) of each drug and the drugs in combination against
      M. tuberculosis H37Rv were determined, and the synergetic activities according to
      the fractional inhibitory concentration (FIC) formula was calculated. Female
      BALB/C mice were infected intravenously with 0.2 mg/L portions containing 5 * 105
      CFU of the MDR clinical isolate 2931. One day after the infection, 6 mice were
      sacrificed and the numbers of CFU in the lungs and spleens were determined. The
      remaining mice were allocated either to untreated group or to drug-treated groups
      (6 mice per group). Thirty days post-infection, both untreated and treated mice
      were sacrificed and the CFU counted. RESULTS: Clofazimine in combination with the
      10 antituberculosis drugs resulted in two- to eight fold reduction in MIC. The
      FIC of clofazimine (Cfz) in combination with p-aminosalicylic acid (PAS),
      protionamide (Pto), clarithromycin (Clr), and capreomycin were less than 0.5,
      suggesting a synergic interaction against M. tuberculosis H37Rv. All the drug
      treatments reduced the numbers of CFU in the lungs and spleens compared with the
      numbers in the untreated controls. Of the individual drugs, Cfz was the most
      effective on day 30, with a mean CFU count decrease of 1.82 and 2.32 lg10, in
      comparison with that of the untreated control. The Cfz-Clr (clarithromycin)
      combination showed significantly greater activity than the control or Clr alone,
      with a mean CFU count decrease of 1.30 and 1.91 lg, in comparison with that of
      the Clr treatment. Cfz-Clr was slightly more active than Cfz alone, but not at a
      statistically significant level. CONCLUSIONS: The activity of clofazimine was
      enhanced by the addition of clarithromycin. These observations are important for
      the therapy of multidrug-resistant tuberculosis.

PMID- 21092636
TI  - [The expression variations of connective tissue growth factor and cyclinD1 in
      pulmonary vascular remodeling induced by cigarette smoke in rats].
AB  - OBJECTIVE: To investigate the expression variations of connective tissue growth
      factor (CTGF) and cyclin D1 in pulmonary vasculature in rats exposed to cigarette
      smoke and their roles in pulmonary vascular remodeling. METHODS: Twenty-four male
      Wistar rats were randomly divided into 4 groups: 1 control group (C group) and 3
      smoke exposure groups (S2w, S4w, S8w group). Arterial partial pressure of oxygen
      was measured. Pulmonary artery remodeling was observed by Hematoxylin-Eosin
      staining and the percentage of muscularised small pulmonary arteries.
      Immunohistochemistry methods were performed to observe CTGF and cyclin D1
      expressions in pulmonary artery smooth muscle. Real time quantitative RT-PCR and
      Western blot analysis were used for detection of mRNA and protein expressions in
      pulmonary artery smooth muscle. RESULTS: There was no significant difference in
      arterial partial pressure of oxygen among all groups. The percentage of
      muscularised small vessels and W/T were significantly increased in S2w, S4w and
      S8w group compared to control group (P < 0.05). Compared to control group,
      significant increases of CTGF and cyclinD1 expressions in smoke exposure groups
      were observed (P < 0.05). The expressions of CTGF and cyclinD1 were significantly
      positively correlated with the severity of pulmonary vascular muscularization,
      and there was statistically positive correlation between the expression of CTGF
      and cyclinD1. CONCLUSION: CTGF and cyclinD1 expressions significantly were
      upregulated in pulmonary arteries from rats exposed to cigarette smoke (2-8w) and
      there was a significant positive correlation between their expressions. Their
      expression variations may be associated with abnormal proliferation of pulmonary
      artery smooth muscle cells induced by cigarette smoke.

PMID- 21092637
TI  - [A guinea pig model of latent Mycobacterium tuberculosis H37Rv infection].
AB  - OBJECTIVE: To establish the guinea pig model of latent Mycobacterium tuberculosis
      (MTB) H37Rv infection, and to study the multiplication dynamics of MTB in vivo,
      and the relationship between latent MTB infection and PPD skin test. METHODS:
      Sixty-two guinea pigs were randomly divided into the model group (n = 42) and the
      control group (n = 20), and the model group was subdivided into a 4 weeks group
      (n = 12), an 8 weeks group (n = 21) and a 12 weeks group (n = 9), challenged by
      500 CFU H37Rv with restored toxicity. After 2 weeks challenge, the model groups
      were treated with isoniazid (INH, 10 mg/kg) + pyrazinamidum aldinamide (PZA, 40
      mg/kg) for 4 weeks, 8 weeks and 12 weeks respectively. The natural recurrence of
      tuberculosis was observed in the model 4 weeks group, and the natural and induced
      recurrence by dexamethasone was observed in the model 8 weeks group and 12 weeks
      group. PPD skin test, the pathologic changes, and MTB quantity of organs were
      observed. RESULTS: In the control group, the average MTB quantity of spleen was
      3.3 lg CFU after 2 weeks challenge, and the average MTB quantity of spleen and
      lung in guinea pigs were 4.5 lg CFU and 1.8 lg CFU respectively after 6 weeks
      challenge, and they reached 5.3 lg CFU and 5.4 lg CFU at 18 weeks respectively.
      The latent MTB infection of the model 4 weeks group recurred naturally 12 weeks
      after stopping treatment. The latent MTB infection of the model 8 weeks group
      recurred naturally and by dexamethasone treatment. The latent MTB infection of
      the model 12 weeks group did not recur naturally, but dexamethasone induced
      recurrence. The positive PPD response correlated with recurrence. CONCLUSIONS: A
      latent MTB infection model was established successfully by H37Rv challenge and
      treatment with INH and PZA. The latent MTB infection may recur naturally or by
      induction. The PPD response was related to tuberculosis recurrence.

PMID- 21092638
TI  - [CD4(+)Foxp3(+) regulatory T cells in inflammation and emphysema after smoking
      cessation in rats].
AB  - OBJECTIVE: To evaluate the expression of Treg in a cigarette smoke-induced rat
      model of emphysema and after smoking cessation in the rats. METHODS: Fifty male
      Wistar rats were randomly divided into control group 1 (12 weeks), control group
      2 (24 weeks), smoke-exposure group 1 (12 weeks), smoke-exposure group 2 (24
      weeks) and smoking cessation group, with 10 rats in each group. Alveolar airspace
      enlargement was observed by hematoxylin-eosin (HE) staining. IL-8 and TNF-alpha
      levels in bronchoalveolar lavage fluid (BALF) were tested by ELISA. The
      proportion of CD4(+)Foxp3(+) Treg in peripheral blood and lungs of rats was
      determined by flow cytometry. The mRNA expression of Foxp3 was measured by real
      time PCR. Comparisons of the data between different groups were performed using
      one-way ANOVA, and SNK and Games-Howell test was used for comparison between 2
      groups. RESULTS: The mean linear intercept (MLI) in smoke-exposure group 1 and
      group 2 [(64.9 +/- 5.3) um, (77.9 +/- 11.5) um] was higher than those in the
      control group 1 and group 2 [(39.0 +/- 3.8) um, (40.3 +/- 2.7) um], all P < 0.01.
      Compared with smoke-exposure group 2, the MLI in smoking cessation group (71.5 +/
      5.8) um showed a lower value (P < 0.01), but still higher than that in smoke
      exposure group 1 (P < 0.01). The IL-8 and TNF-alpha levels in BALF of smoke
      exposure group 1 and group 2 [(68 +/- 17) ng/L, (85 +/- 16) ng/L], [(14.1 +/-
      1.8) ng/L, (20.1 +/- 8.7) ng/L] were higher than those in control group 1 and
      group 2 [(44 +/- 8) ng/L, (43 +/- 9) ng/L], [(6.3 +/- 2.3) ng/L, (5.8 +/- 1.6)
      ng/L], all P < 0.05. The IL-8 and TNF-alpha levels were not statistically
      different between in smoking cessation group (56 +/- 6) ng/L, (14.7 +/- 4.7) ng/L
      and smoke-exposure group 1. The percentage of Treg in the lungs of smoke-exposure
      group 1 and group 2 [(6.6 +/- 0.8)%, (5.3 +/- 0.9)%] was significantly decreased
      as compared to control group 1 and group 2 [(9.0 +/- 1.0)%, (9.6 +/- 0.9)%], all
      P < 0.01. The percentage of Treg in lungs was not statistically different between
      smoke-exposure group 1 and smoking cessation group (7.2 +/- 0.6)%. In peripheral
      blood, there was no significant difference between groups in the percentage of
      Treg. In the lung, Foxp3 mRNA expression in smoke-exposure group 1 and group 2
      [(17 +/- 7), (9 +/- 7)] was less than that in control group 1 and group 2 [(39 +/
      6), (42 +/- 7)], all P < 0.01. The Foxp3 mRNA expression was not statistically
      different between smoke-exposure group 1 and smoking cessation group (21 +/- 9).
      No significant differences in peripheral blood Foxp3 mRNA expression was found
      between groups. CONCLUSIONS: Decreased Treg was present in lungs of cigarette
      smoke-induced model of emphysema despite 12 weeks' smoking cessation, suggesting
      that down-regulation of Treg may be involved in the amplified and persistent
      inflammation after smoking cessation.

PMID- 21092639
TI  - [The progress in clinical applications of Extracorporeal Membrane Oxygenation].

PMID- 21092640
TI  - [The role of nitrates in prognosis improvement of coronary heart disease: yes or
      no].

PMID- 21092641
TI  - [Chinese expert consensus document on the organic nitrates in cardiovascular
      disease].

PMID- 21092642
TI  - [Association between delayed enhancement on cardiac magnetic resonance imaging
      and arrhythmia in patients with hypertrophic cardiomyopathy].
AB  - OBJECTIVE: to observe the association between myocardial fibrosis, detected by
      delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) and arrhythmia
      in patients with hypertrophic cardiomyopathy (HCM). METHODS: forty-eight
      untreated HCM patients who underwent Cine MR, DE-MRI, 24 h ambulatory Holter
      electrocardiogram and ECG examinations were recruited. Extent of myocardial
      fibrosis (fibrosis mass/total LV mass) was assessed using DE imaging. Association
      between arrhythmias including premature ventricular complexes (PVCS >= 200),
      supra-ventricular tachycardia (SVT), non-sustained ventricular tachycardia
      (NSVT), atrio-ventricular block (AVB) and intra-ventricular block (IVB) detected
      by Holter monitoring and ECG with regard to delayed enhancement (DE) on contrast
      enhanced CMR was analyzed. RESULTS: myocardial fibrosis was detected in 35
      patients. Incidence of arrhythmia was significantly higher in patients with DE
      than in patients without DE (P < 0.05). Extent of myocardial fibrosis was
      significantly associated with the QRS duration (r = 0.33, P < 0.001). CONCLUSION:
      myocardial fibrosis detected by DE-CMR was associated with arrhythmia in patients
      with HCM. DE-CMR might be helpful to detect high-risk HCM patients prone to
      arrhythmia.

PMID- 21092643
TI  - [Clinical characteristics and hypertrophic segments distribution of patients with
      hypertrophic cardiomyopathy].
AB  - OBJECTIVE: to analyze the clinical data and hypertrophic segments distribution of
      patients with hypertrophic cardiomyopathy (HCM). METHODS: clinical data including
      signs and symptoms, electrocardiogram and echocardiography were collected. All
      patients were imaged with cardiac magnetic resonance imaging (CMR). RESULTS: from
      March 2004 to March 2007, 225 consecutive patients [163 males, mean age (50.4 +/-
      14.5) years] with CMR defined HCM were included in this study, positive familial
      history was obtained in 73 patients, 50 patients were associated with
      hypertension, 14 patients with coronary artery disease and 5 patients with
      diabetes mellitus, 28 patients were asymptomatic, 197 patients were symptomatic,
      and 11 patients with syncope. Electrocardiogram abnormalities occurred in 216
      patients. Systolic murmurs were present in 126 patients. Echocardiography
      examination evidenced left ventricular outflow obstruction in 95 patients, mitral
      insufficiency in 32 patients, 32.1% segments were hypertrophied, asymmetrical
      hypertrophy presented in 222 patients and symmetrical hypertrophy in 3 patients.
      The left atrial dimension was (39.4 +/- 8.3) mm, and left ventricular diastolic
      dimension was (47.8 +/- 5.5) mm in this cohort. Apical hypertrophy occurred in 67
      patients. The thickness of ventricular septum was (24.3 +/- 5.3) mm in
      obstructive HCM and (21.6 +/- 4.6) mm in non-obstructive HCM (P < 0.05). The
      thickness of hypertrophy apical segment was (15.6 +/- 3.4) mm. CONCLUSIONS: HCM
      in Chinese patients is characterized by the high prevalence among men and late
      onset of presentation. Combining clinical, electrocardiogram, echocardiographic
      and CMR results are of importance for correctly diagnosing HCM in daily practice.

PMID- 21092644
TI  - [Clinico-pathological evaluation of restrictive cardiomyopathy].
AB  - OBJECTIVE: restrictive cardiomyopathy (RCM) is characterized by impairment of
      ventricular filling during diastole with preserved systolic function. The
      clinical and histopathological profile on endomyocardial biopsy of 25 consecutive
      patients with RCM was analyzed in this study. METHODS: twenty-five patients with
      diagnosis of RCM and underwent endomyocardial biopsy (EMB) were enrolled in the
      study. The clinical characteristics, electrocardiogram, serum chemistry, right
      heart catheter and cardiac pathology results were obtained. RESULTS: heart
      failure symptom was present in all 25 patients and left ventricular size and
      function were normal or near normal while serum brain natriuretic peptide (577
      pg/ml) was moderately elevated. Right atrial and ventricular end-diastolic as
      well as pulmonary capillary wedge pressures derived from right heart catheter
      examination were increased. Amyloid deposition were evidenced in 16 and
      eosinophilic myocarditis in 2 patients upon pathological examination of EMB. In
      the remaining 7 patients, 3 were diagnosed idiopathic RCM, 2 were diagnosed as
      amyloidosis by biopsy from non-cardiac tissue and etiology remained unknown in 2
      patients. Thus, conclusive diagnosis was made on EMB samples in 84% (21/25)
      patients of RCM. CONCLUSION: RCM may result from various local and systemic
      disorders. EMB is helpful for identifying the underlying etiology.

PMID- 21092645
TI  - [Alteration of Th17 cells in mice with coxsackie virus induced myocarditis].
AB  - OBJECTIVE: to observe the alteration of T helper cells 17(Th17) in mice with
      acute viral myocarditis (VMC) induced by coxsackie virus B3 (CVB3), explore the
      role of Th17 in mice VMC. METHODS: CVB3 or PBS was peritoneally injected to
      Balb/c male mice. Pathological scores were determined in hematoxylin-eosin
      stained sections and flow cytometric analysis was used to evaluate the
      frequencies of Th17 subsets in CD4(+) T cells on 7, 14, 21, 28 and 42 days after
      virus injection. RESULTS: there were significant difference of the pathological
      scores between the VMC mice and the control ones (P < 0.05). The pathological
      scores of 7 d VMC subgroup were higher (1.8 +/- 0.5) than those of 0 d VMC
      subgroup, and the scores of 14 d subgroup were highest (2.8 +/- 0.4) among the
      six subgroup of VMC mice, and then showed a decline tendency from 21 d group.
      Statistical difference of the proportion of Th17 cells were seen between the VMC
      and controls on different time points (P < 0.05). When compared with the 0 d VMC
      subgroup the proportion of spleen Th17 cells increased in 7 d VMC subgroup [(2.23
      +/- 0.89)%], and peaked on 28 d [(5.00 +/- 0.81)%]. The results of Th17
      proportion were lower than those of the 28 d subgroup. CONCLUSIONS: our data show
      that differentiated Th17 cells might be involved in the inflammation process of
      CVB3 induced VMC in mice.

PMID- 21092646
TI  - [Retrograde percutaneous recanalization of chronic total occlusion of the
      coronary arteries via epicardial coronary collateral artery in 5 patients].
AB  - OBJECTIVE: to explore the feasibility of percutaneous recanalization by
      retrograde approach via epicardial collaterals. METHODS: retrograde percutaneous
      coronary intervention (PCI) via epicardial collaterals was performed in 5
      patients with previously failed antegrade PCI from April 2009 to November 2009. 7
      F guiding catheters were engaged in donor artery. Hydrophilic wires and
      microcatheters were crossed to the distal ends of chronic total occlusion (CTO)
      lesions via epicardial collaterals. Four retrograde wires were exchanged into
      stiffer wires and further crossed the CTO, eventually went into the 6 F antegrade
      guiding catheters and were jailed by a 2.5 mm balloon. After dilatations of
      retrograde balloons, the lesions were crossed by antegrade wires, and finalized
      by conventional PCI method. One case was recanalized with retrograde wire
      trapping technique and another case was recanalized by reverse CART technique.
      RESULTS: the epicardial collaterals were reached from left anterior descending
      branch (LAD) to distal right coronary artery (RCA) via apex in 3 patients, from
      left circumflex branch via left atrium branch to posterior descending artery and
      RCA in 1 patient and from obtuse marginal artery to diagonal artery and LAD in 1
      patient. CTO was successfully recanalized and stents were implanted in 4 patients
      and failed in 1 patient despite successful wire positioning to the distal end of
      CTO. There was no procedure-induced cardiovascular event in all cases.
      CONCLUSIONS: epicardial collaterals may not be used as a routine route in
      retrograde approach PCI due to the potential risk of myocardial rupture and
      pericardial tamponade. In some cases with unavailable or unsuitable septal
      collaterals, epicardial collaterals may be used as an alternative route for CTO
      recanalization.

PMID- 21092647
TI  - [Plasma asymmetric dimethylarginine and cystatin C levels in patients with
      coronary artery disease].
AB  - OBJECTIVE: To compare plasma asymmetric dimethylarginine (ADMA), an endogenous
      nitric oxide synthase inhibitor, and cystatin C levels in patients with or
      without coronary artery disease (CAD). METHODS: We recruited 87 CAD patients (39
      with acute myocardial infarction and 48 with unstable angina pectoris) and 51 non
      CAD controls. Plasma ADMA was measured by HPLC, cystatin C by particle-enhanced
      immunonephelometric assay (N Latex cystatin C, Dade Behring) with nephelometer
      (BNII, Dade Behring). CAD patients were further divided into low cystatin C group
      (< 1.0 mg/L, 36 cases) and high cystatin C group (> 1.0 mg/L, 51 cases). RESULTS:
      (1) The plasma levels of ADMA [(0.47 +/- 0.15) umol/L vs. (0.37 +/- 0.15)
      umol/L], SDMA [(0.39 +/- 0.19) umol/L vs. (0.28 +/- 0.12) umol/L] and cystatin C
      [(1.16 +/- 0.32) mg/L vs. (0.73 +/- 0.16) mg/L] were significantly higher in CAD
      patients than in controls (all P < 0.05). The plasma L-Arg was significantly
      lower in CAD patients than in controls [(59.4 +/- 19.4) umol/L vs. (83.7 +/-
      19.6) umol/L, P < 0.05]. (2) Plasma ADMA was similar in CAD patients with low
      cystatin C level and controls [(0.42 +/- 0.12) umol/L vs. (0.39 +/- 0.15) umol/L,
      P = 0.251] and Plasma ADMA was significantly higher in CAD patients with high
      cystatin C level than in controls [(0.50 +/- 0.17) umol/L vs. (0.39 +/- 0.15)
      umol/L, P < 0.05]. CONCLUSION: ADMA levels were significantly increased only in
      CAD patients with elevated cystatin C levels but not in CAD patients with normal
      renal function. The reported relationship between coronary heart disease and ADMA
      may not be direct, but could be secondary due to reduced renal function.

PMID- 21092648
TI  - [Early repolarization syndrome and recurrent syncope in two Chinese pedigrees].
AB  - OBJECTIVE: to investigate the clinical characteristics in two families with early
      repolarization syndrome (ERS) and recurrent syncope. METHOD: all family members
      including the probands were screened with routine clinical examination,
      electrocardiography, echocardiography, Holter recording, chest x-ray, head-up
      tilt test and blood biochemistry. RESULTS: there was no clinical evidence of
      organic heart disease in all members from the two families. Proband 1 showed
      recurrent syncope, ERS and repeated torsade de pointes ventricular tachycardia
      and ventricular fibrillation were documented with resting ECG. ERS was detected
      in one brother, one nephew and one son from him and all were free of cardiac
      events including syncope, cardiac arrest and sudden cardiac death. Proband 2
      showed recurrent syncope, ERS and ST segment arched upward elevation in V(1)-V(3)
      were documented by ECG. His father suffered sudden cardiac death at the age of 65
      and asymptomatic ERS was detected in one of his nephew. CONCLUSIONS: ERS is not
      always linked with benign clinical course and can sometimes lead to repeated
      syncope, torsade de pointes ventricular tachycardia and ventricular fibrillation.
      Pedigree research is of importance for ERS.

PMID- 21092649
TI  - [Arrhythmia after a positive head-up tilt table test].
AB  - OBJECTIVE: to study the characteristics of arrhythmia after a positive head-up
      tilt table test (HUTT). METHODS: head-up tilt table test (BHUT) or sublingual
      nitroglycerin-provocation head-up tilt table test (SNHUT) were performed in 1374
      patients at the Second Xiangya Hospital of Central South University from March of
      2001 to August of 2009. Arrhythmias were recorded in 169 patients after a
      positive HUTT [57 male, age 6 - 65 years, 86 children < 18 years, mean age (23.1
      +/- 14.8) years]. RESULTS: arrhythmias developed in 75 patients (44.38%) post a
      positive BHUT and in 94 patients (55.62%) post a positive SNHUT. Major types of
      arrhythmias were sinus bradycardia (143/169, 84.62%), junctional escape rhythm
      (55/169, 32.54%) and sinus arrest (26/169, 15.38%). Sinus bradycardia was more
      common in adult (P < 0.01). Occurrence of junctional escape rhythm and sinus
      arrest was not affected by age, gender and test mode. Arrhythmia and the
      manifestation of syncope or pre-syncope occurred simultaneously in 77 (45.56%)
      patients and mainly in BHUT, while arrhythmia appeared later than the syncope
      manifestation in 92 (54.44%) patients and mainly in SNHUT (P < 0.05). Arrhythmia
      and blood pressure reduction occurred simultaneously in 84 (53.50%) cases and
      mainly in BHUT, while arrhythmia appeared later than reduction of blood pressure
      in 73 (46.50%) cases and mainly in SNHUT (P < 0.01). CONCLUSIONS: (1) the common
      types of arrhythmia were sinus bradycardia, junctional escape rhythm and sinus
      arrest after a positive HUTT. Occurrence of sinus arrest was not affected by age,
      gender and test mode. (2) In BHUT, arrhythmia occurred mostly simultaneously with
      the manifestation of syncope or pre-syncope and blood pressure reduction, while
      arrhythmia appeared later in SNHUT.

PMID- 21092650
TI  - [Statin reduced triglyceride level via activating peroxisome proliferator
      activated receptor alpha and upregulating apolipoprotein A5 in
      hypertriglyceridemic rats].
AB  - OBJECTIVE: to explore the potential role of apolipoprotein A5 (apoA5) on the
      hypertriglyceridemia (HTG)-lowering effects of statin. METHODS: twenty-four
      Sprague-Dawley rats were randomized into 3 groups: (1) control group (n = 8),
      with no special treatment; (2) HTG group (n = 8), treated with 10% fructose water
      for 6 weeks; (3) statin group (n = 8), treated with 10% fructose water for 2
      weeks and cotreated with atorvastatin 10 mg*kg(-1)*d(-1) for another 4 weeks.
      Body weight, fasting plasma lipids and the hepatic expressions of apoA5 and
      peroxisome proliferator activated receptor (PPAR)alpha were determined. In
      separate in vitro experiments, we tested the effects of atorvastatin on TG and
      the expressions of apoA5 and PPARalpha in HepG2 cells. RESULTS: (1) at 6 weeks,
      plasma TG was higher in rats in HTG group than in controls, which was
      significantly reduced in statin group (both P < 0.05). (2) Rat hepatic apoA5
      expression in HTG group was significantly lower than in control group and was
      significantly higher in statin group than in HTG group (both P < 0.05). (3)
      Similarly, rat PPARalpha mRNA expression in HTG group was lower than in control
      group and was higher in statin group than in HTG group (both P < 0.05). (4)
      Statin significantly upregulated the expressions of apoA5 and PPARalpha and
      decreased TG in HepG2 cells. The above effects induced by statin was blocked in
      the presence of PPARalpha inhibitor. CONCLUSIONS: upregulation of apoA5
      expression contributes to TG lowering effect of statin via PPARalpha signaling
      pathway.

PMID- 21092651
TI  - [Rosuvastatin enhances the protective effects of ischemic postconditioning on
      myocardial ischaemia-reperfusion injury in type 2 diabetic rat].
AB  - OBJECTIVE: to investigate the combined effect of rosuvastatin (RSV) and ischemic
      postconditioning (PC) on myocardial ischemia-reperfusion (I/R) injury in a type 2
      diabetic rat model. METHODS: type 2 diabetic (induced by streptozotocin plus
      nicotinamide) rats, undergoing 30 min ischemia and 120 min reperfusion, were
      divided into six groups (n = 10 each): Sham, I/R without other interventions, RSV
      before reperfusion, PC with 3 cycles of 10 s reperfusion and 10 s ischemia, RSV +
      PC and RSV + PC + PI3-K inhibitor LY294002. Myocardial infarct size (IS),
      ultrastructural change and myocardial expression of phosphorylated eNOS/total
      eNOS were determined. RESULTS: IS and ultrastructural damages were all
      significantly reduced and myocardial eNOS phosphorylation was significantly
      increased in RSV and PC groups compared with the I/R group (all P < 0.05) these
      beneficial effects were further enhanced by RSV + PC (all P < 0.05 vs. RSV and
      PC, respectively). The beneficial effects were significantly attenuated by PI3K
      inhibitor LY294002. CONCLUSIONS: the results indicate that RSV + PC could
      alleviate myocardial ischemia-reperfusion injury in this type 2 diabetic model by
      activating PI3K/AKT/eNOS signaling pathway.

PMID- 21092652
TI  - [Effect of ischemia preconditioning on pro- and anti- angiogenic molecule
      expression and functional arteries formation].
AB  - OBJECTIVE: to observe the effect of ischemia preconditioning (IPC) on the
      expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and
      arteriogenesis. METHODS: rat heart IPC model was made by 4 circles of occluding
      the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF
      B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6,
      12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD
      ligation 24 h after IPC, 14 days later, the anti-SM-alpha-actin antibody was used
      to detect the mature neovascularization in the border of the infracted area.
      RESULTS: VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic
      area in IPC group compared with the control group (P < 0.05). Density of mature
      arteries was also significantly increased in IPC plus MI group than that in MI
      group (P < 0.05). CONCLUSION: IPC promoted the formation of mature new arteries
      which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.

PMID- 21092654
TI  - [Evaluation of viable myocardium by two-dimensional strain imaging combined with
      adenosine stress echocardiography in dogs underwent experimental
      ischemia/reperfusion injury].
AB  - OBJECTIVE: to explore the feasibility of evaluating viable myocardium with two
      dimensional strain imaging combined with adenosine stress echocardiography.
      METHODS: acute myocardial infarction and reperfusion model was made by ligating
      anterior descending coronary artery for 90 minutes followed by 120-minute
      reperfusion in 15 healthy mongrel dogs. Images were acquired at baseline and
      after reperfusion. Adenosine was then infused and image acquisition repeated.
      Regional peak-systolic strain in radial, circumferential and longitudinal motion
      on anterior wall and anterior septum were measured. TTC staining served as a
      "gold standard" to define viable and nonviable myocardium. The ratio of infarct
      area (S(N)) to total area (S) was calculated and viable myocardium was defined
      with S(N)/S <= 50%. RESULTS: at baseline, RS(peak sys), CS(peak sys) and LS(peak
      sys) were similar between viable (n = 37) and nonviable myocardial segments (n =
      53) and significantly decreased after reperfusion in both viable and nonviable
      myocardial segments. Compared with values obtained after reperfusion, LS(peak
      sys) and RS(peak sys) remained unchanged in nonviable myocardial segments and
      significantly increased in viable myocardial segments after adenosine (P < 0.05).
      Post adenosine RS(peak sys) was negatively correlated with S(N)/S and CS(peak
      sys) and LS(peak sys) were positively correlated with S(N)/S. With DeltaRS(peak
      sys) (before and after adenosine) >= 13.5%, the sensitivity was 83.8% and
      specificity was 83.0% for distinguishing viable from nonviable myocardial
      segment. With DeltaLS(peak sys) >= 11% as cutoff value, the sensitivity was 78.4%
      and specificity was 88.7% for distinguishing viable from nonviable myocardial
      segment. Combining DeltaRS(peak sys) and DeltaLS(peak sys), the sensitivity and
      specificity for distinguishing viable from nonviable myocardial segment were
      91.9% and 79.2%, respectively. CONCLUSIONS: two-dimensional strain imaging
      combined with adenosine stress echocardiography could quantitatively identify
      viable and nonviable myocardium.

PMID- 21092653
TI  - [Value of in vivo monitoring of abdominal aortic atherosclerosis by high field
      magnetic resonance imaging in apoE-/- mice fed a high fat diet or infused with
      angiotensin II].
AB  - OBJECTIVE: to explore the value of in vivo dynamic monitoring of abdominal aortic
      atherosclerosis (AS) by high field magnetic resonance (MR) imaging (MRI) in apoE
      /- mice fed a high fat diet or infused with angiotensin. METHODS: high fat diet
      or angiotensin II infusion was applied to apoE-/- mice for establishment of
      abdominal aortic atherosclerosis model. Abdominal aorta MRI was performed at 3
      time points (baseline, 3 and 6 months) in 13 high fat diet fed apoE-/- mice aged
      10-12 months and 3 wild-type control mice; 10 apoE-/- mice aged 6 months were
      infused with angiotensin II (1000 or 500 ng * kg(-1)* min(-1), n = 5 each) or
      saline for 14 d through Osmotic minipump. The abdominal aortic artery MRI was
      performed at baseline and 14 d after infusion. Black blood sequences of FLASH T1
      weighted images and Proton density weighted-T2 weighted dual echo images were
      obtained. At each observation time post MRI, mice (n = 3, 5 and 5 for high fat
      diet group and n = 5 and 5 for angiotensin II infusion group) were sacrificed for
      pathological examination of the abdominal artery. RESULTS: (1) the abdominal
      aorta atherosclerosis was identified in both high fat diet and angiotensin II
      treated apoE-/- mice but in WT controls. Lesion progression was documented in
      high fat diet fed apoE-/- mice characterized by significantly increased vessel
      wall (a marker of atherosclerotic burden, F = 29.94, P < 0.05) and gradually
      increased plaque signal in PDW and T2W images. Results derived from MRI
      corresponded histopathology findings in high fat diet fed apoE-/- mice
      (correlative coefficient = 0.84, 0.95, 0.90, P < 0.05, respectively). Both MRI
      and histology showed increased lipid composition and decreased fibrotic
      composition in these mice. (2) The vessel wall area increased significantly
      [(1.21 +/- 0.21) mm(2) vs. (2.65 +/- 0.48) mm(2), P < 0.05] and the abdominal
      aortic dissection aneurysms was identified in apoE-/- mice infused with high
      angiotensin II. The vessel wall area also increased [(0.85 +/- 0.11) mm(2) vs.
      (1.01 +/- 0.17) mm(2), P < 0.05] in low angiotensin II infused apoE-/- mice and
      the coefficient between MR and histopathology is 0.934. CONCLUSION: abdominal
      aortic unstable plaque model could be established by both high fat diet and
      angiotensin II infusion in apoE mice, angiotensin II infusion can transiently
      accelerate the progression of AS and can induce abdominal aortic dissection.
      Serial MR black blood sequences could demonstrate the development and progression
      of atherosclerosis in mouse abdominal aorta with excellent agreement to
      histopathology finding in terms of atherosclerotic burden and plaque composition.
      Thus, MRI appears to be a useful tool for in vivo AS plaque dynamic monitoring in
      mice.

PMID- 21092655
TI  - [Association between myocardial calpain activation and apoptosis in
      lipopolysaccharide-induced septic mouse model].
AB  - OBJECTIVE: in septic mice, myocardial calpain was activated and induced caspase-3
      activation, the association between calpain activation and apoptosis was explored
      in this experiment. METHODS: in in vivo model, adult C57 mice were injected with
      lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Myocardial calpain and
      caspase-3 activities, protein levels of calpain-1, calpain-2, calpastatin, Bcl-2
      and Bid were detected by Western blot analysis and myocardial apoptosis was
      detected by TUNEL, myocardiac function was evaluated by Langendorff system. In in
      vitro model, adult rat cardiomyocytes were incubated with LPS (1 microg/ml) or co
      incubated with calpain inhibitor-III (10 micromol/L), calpain activity, caspase-3
      activity, protein levels of Bcl-2 and Bid, and cardiomyocyte apoptosis were
      detected. RESULTS: in septic mice, myocardial calpain and caspase-3 activity were
      increased up to 2.7- and 1.8-folds, respectively. Both calpain inhibitor-III and
      PD150606 significantly attenuated the increase of caspase-3 activity. Myocardial
      protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were similar
      between control and septic mice, and no cleavage of both Bcl-2 and Bid was found
      in septic mice. Calpain inhibitor-III significantly improved myocardial function
      in septic mice. In in vitro model, calpain and caspase-3 activities were
      increased after 4 h LPS treatment, co-treatment with calpain inhibitor-III
      prevented caspase-3 activity increase, protein Bcl-2 and Bid were similar between
      normal cardiomyocytes and LPS-treated cardiomyocytes. Cardiomyocyte apoptosis was
      similar in in vivo and in vitro septic models. CONCLUSION: myocardial calpain
      activity is increased in LPS induced septic mice, subsequent caspase-3 activation
      may contribute to myocardial dysfunction in septic mice without aggravating
      myocardial apoptosis and Bcl-2 and Bid are not involved on calpain induced
      caspase-3 activation in our model.

PMID- 21092656
TI  - [The relationship between occupational physical activity intensity and peripheral
      arterial disease].
AB  - OBJECTIVE: to explore the relationship between occupational physical activity and
      peripheral arterial disease (PAD)assessed by ankle-brachial index (ABI). METHODS:
      data including ABI, occupational physical activity intensity, health history,
      medication use, blood biochemistry and physical examinations derived from 16 446
      subjects from 9 areas throughout China were analyzed. Univariate and multivariate
      adjusted logistic regression analysis were used for the data analyses. RESULTS:
      occupational physical activity intensity was classified into 5 levels as jobless,
      very light, light, moderate and heavy intensity. With the increasing of physical
      activity intensity, the risk of PAD gradually decreased (P(trend) < 0.05). In
      comparison with jobless group, the ORs of PAD for other groups were 0.65 (95%CI:
      0.52, 0.82), 0.70 (95%CI: 0.56, 0.87), 0.57 (95%CI: 0.44, 0.73), 0.65 (95%CI:
      0.53, 0.80) respectively. After adjusting for gender, age, smoke,
      obesity/overweight, the history of hypertension, hypercholesterolemia, diabetes,
      cardiovascular disease and stroke, the ORs were 1.02 (95%CI: 0.80, 1.31), 0.91
      (95%CI: 0.72, 1.15), 0.92 (95%CI: 0.70, 1.19), 0.90 (95%CI: 0.72, 1.12) (P(trend)
      < 0.05). CONCLUSION: PAD risk reduced in proportion with increasing occupational
      physical activity.

PMID- 21092657
TI  - [One case of coronary slow flow complicated with episodes of ST segment elevation
      followed by complete atrioventricular block and syncope].

PMID- 21092658
TI  - [A case with severity stenosis of left main artery manifested with recurrent
      syncope].

PMID- 21092659
TI  - [Two cases of interventional retrieval of broken vein catheters in Superior vena
      cava and inferior vena cava].

PMID- 21092660
TI  - [Myocardial late gadolinium enhancement cardiovascular magnetic resonance in two
      patients with cardiac amyloidosis].

PMID- 21092661
TI  - [A case analysis of right atrial appendage tachycardia misdiagnosed as sinus
      tachycardia].

PMID- 21092662
TI  - [Clinical and pathological characteristics of atypical Fabry disease].

PMID- 21092664
TI  - [Advances and refinements in voice medicine].

PMID- 21092663
TI  - [Recent research progress and updates of PRKAG2 cardiac syndrome].

PMID- 21092665
TI  - [Sternum-hyoid muscle transposition and arytenoid adduction for unilateral vocal
      cord paralysis].
AB  - OBJECTIVE: To explore the therapeutic effect of sternum-hyoid muscle
      transposition and arytenoid adduction for unilateral vocal cord paralysis (UVCP).
      METHODS: Included in this study were 19 patients with UVCP lasted for 12 months
      to 15 years. The surgical technique was as follows. The thyroid cartilage was
      engaged with a skin hook and gently rotated anteriorly. The lateral-inferior
      corner of the thyroid cartilage was exposed and the muscular process of the
      arytenoid was identified. Then, the thyroid lamina on the involved side was
      parasagittally separated 5 mm off the midline. The inner perichondrium was
      carefully freed from the overlying thyroid cartilage. The lamina was retracted
      laterally, and a 3-0 prolene suture was placed through the muscular process and
      tied to the cricoid cartilage at the origin of the lateral cricoarytenoid muscle.
      A bipedicled strap muscle flap was then transposed into the space between the
      lamina and the inner perichondrium. Pre- and postoperative voice evaluations
      measured mean fundamental frequency, jitter, shimmer, harmonic ratio and maximal
      phonation time, as well as assessments of voice quality. RESULTS: Vocal
      improvement was obtained in 100% (19 of 19) of patients. Immediately after the
      operation, the ingression could be observed in vocal cord membrane and vocal
      process, vocal cord volume was amplified. There was a significant difference (P <
      0.05) in all parameters (fundamental frequency, jitter, shimmer, harmonic ratio
      and maximal phonation time) between pre- and postoperative voice evaluations
      measured mean. There was no significant difference (P > 0.05) in voice
      evaluations measured mean between 2 months and 12 months after operation in all
      patients. No major complications were noted in any patient. CONCLUSION: Sternum
      hyoid muscle transposition and arytenoid adduction for unilateral vocal cord
      paralysis is simple and convenient, no immune rejection, and the long-term result
      is stable.

PMID- 21092667
TI  - [Design of standard voice sample text for subjective auditory perceptual
      evaluation of voice disorders].
AB  - OBJECTIVE: To design a speech voice sample text with all phonemes in Mandarin for
      subjective auditory perceptual evaluation of voice disorders. METHODS: The
      principles for design of a speech voice sample text are: The short text should
      include the 21 initials and 39 finals, this may cover all the phonemes in
      Mandarin. Also, the short text should have some meanings. RESULTS: A short text
      was made out. It had 155 Chinese words, and included 21 initials and 38 finals
      (the final, e, was not included because it was rarely used in Mandarin). Also,
      the text covered 17 light tones and one "Erhua". The constituent ratios of the
      initials and finals presented in this short text were statistically similar as
      those in Mandarin according to the method of similarity of the sample and
      population (r = 0.742, P < 0.001 and r = 0.844, P < 0.001, respectively). The
      constituent ratios of the tones presented in this short text were statistically
      not similar as those in Mandarin (r = 0.731, P > 0.05). CONCLUSIONS: A speech
      voice sample text with all phonemes in Mandarin was made out. The constituent
      ratios of the initials and finals presented in this short text are similar as
      those in Mandarin. Its value for subjective auditory perceptual evaluation of
      voice disorders need further study.

PMID- 21092666
TI  - [Voice fatigue test analysis in secondary school teachers].
AB  - OBJECTIVE: To investigate the status of voice fatigue and throat disease in the
      secondary school teachers in Urumqi. METHODS: This study included 11 689 teachers
      from 109 secondary schools offered by Teaching and Researching Center of Urumqi
      as the second-stage random sampling. Among them, 3217 teachers were selected to
      carry out voice fatigue test and routine examination of throat. For those with
      abnormal routine inspection results, the stroboscopic laryngoscopy were added.
      RESULTS: The failure rate difference of 3217 secondary school teachers voice
      fatigue tests during different periods had statistical significance (F = 202.653,
      P < 0.05). The failure rate difference of voice fatigue test among different
      throat diseases groups had statistical significance (F = 9.516, P < 0.05). There
      was statistical significance in failure rates of the voice fatigue tests between
      908 cases of disease group and 2309 cases of normal group among different genders
      and periods (P < 0.05). Female teachers had higher failure rates than male
      teachers in voice fatigue tests. High failure rates appeared when high volume
      required for male and female teachers in voice fatigue tests. There was
      statistical significance in mean value sound pressure level (MVSPL) and mean
      value fundamental frequency (MVF0) of the voice fatigue tests between different
      gender and periods (P < 0.05). Male teachers had higher MVSPL than female
      teachers, female teachers had higher MVF0 than male teachers. There was
      statistical significance in failure rates of the voice fatigue tests among
      teachers from different tribes in different periods (P < 0.05). The Uighur had
      the highest failure rate, while Han had the lowest. Make further pairwise
      comparisons, failure rates difference of the Han and the Uighur in the voice
      fatigue tests during different periods had statistical significance. Comparison
      among other tribes had no statistical significance (P > 0.05). CONCLUSIONS: Voice
      fatigue is common in secondary school teachers. Female teachers tend to get voice
      fatigue more easily, when required high volume, the voice fatigue is more
      serious. Uighurs teachers have highest degree of voice fatigue.

PMID- 21092668
TI  - [Characterization of vocal fold regeneration after adipose-derived mesenchymal
      stem cells implanting].
AB  - OBJECTIVE: To investigate the treatment for injured vocal folds by implanting
      autologous adipose-derived mesenchymal stem cells (ADSC), and to observe the
      characteristics of lamina propria of the vocal folds and its major extracellular
      matrix (ECM), as well as the growth features of ADSC. METHODS: The lamina propria
      was injured by localized resection in fifty-three vocal folds of thirty-four
      rabbits. Isolation, culture and identification of ADSC were performed in twenty
      rabbits. Three to five days after vocal folds injury, autogeneic ADSC were
      implanted into the injured vocal folds. As control, scaffolds (collagen or
      hyaluronic acid) and none were injected into eighteen and fifteen vocal folds
      respectively. Larynges were harvested at 15 days, 40 days and 3, 6, 12 months
      after operation. The growth and distribution of ADSC were detected by DAPI stain.
      Meanwhile, HE staining was performed for histopathologic research, Masson
      trichrome staining, Alcian Blue staining and immunohistochemical staining were
      used for collagen, hyaluronic acid and fibronectin respectively. RESULTS: ADSC
      showed a spindle-shaped adherent growth, with multi-differentiation potential.
      After implanting into the injured vocal fold, ADSC can survive in vocal fold
      lamina propria. In ADSC implanting group, the morphology and histologic structure
      of vocal folds were similar to normal in six and twelve months after ADSC
      implanting respectively. collagen had an increasing trend in three months, with
      the disorderly distribution in the vocal fold lamina propria, then it became
      decreasing until the twelveth month, when concentration closed to normal,
      however, distribution of collagen was a little irregular. The content of
      hyaluronic acid increased within forty days and distributed in the lamina
      propria, then gradually reduced to normal levels in the following twelve months,
      and limited in the superficial and middle layers of lamina propria, which closed
      to normal. Fibronectin in the lamina propria continued to scattered at the peak
      levels at fortieth day, then decreased in the later twelve months when the
      content became near normal. In the untreated group, vocal fold showed a local
      scar contracture at third month after injury, histology showed large number of
      fibrous tissue (mainly collagen fibers) hyperplasia with a tendency of
      increasing, disorders was also found in vocal fold lamina propria. In the
      scaffold implanting group, the changes were between the two groups above.
      CONCLUSIONS: ADSC are good source of seed cells for vocal fold tissue
      engineering, which have the ability for promoting injured rabbit vocal folds ECM
      secretion, rational distribution and part ordering arrangement. ADSC also play an
      important role in vocal folds reparation and regeneration.

PMID- 21092669
TI  - [Clinical significance of intact canal wall mastoidectomy combined with facial
      recess opening in the treatment of secretory otitis media of children].
AB  - OBJECTIVE: To investigate the clinical significance of intact canal wall
      mastoidectomy combined with facial recess opening in the treatment of secretory
      otitis media of children. METHODS: The clinical data of 17 children (19 ears)
      with recurrent secretory otitis media yet failed tube insertion more than 3
      times, and treated with intact canal wall mastoidectomy combined with facial
      recess opening, in the Department of Otorhinolaryngology Head and Neck Surgery,
      Second Affiliated Hospital of SUN Yat-sen University, were reviewed. And because
      of the eustachian tube dysfunction, 7 ears simultaneously accepted tube
      insertion, which were removed after 1 to 3 months. RESULTS: Pathological
      examination of the lesions in middle ear and mastoid of the 19 ears, revealed
      cholesterol granuloma in 9 ears and inflammatory granulation in 10 ears. All 19
      ears recovered with normal tympanic membranes. There were 16 ears with type A
      tympanogram and 3 ears with type C tympanogram (negative pressure less than 150
      mm H2O). The air-bone gaps were less than 15 dB in 3 months after surgery. There
      was no recurrence in all cases after 2 - 3 years follow-up. CONCLUSIONS: In case
      of recurrent otitis media in children, especially when tube insertion is
      ineffective, intact canal wall mastoidectomy combined with facial recess opening
      can be adopted to clear the lesions thoroughly, and to establish long-time and
      effective ventilation of eustachian tube, tympanic cavity, tympanic antrum, and
      mastoid.

PMID- 21092670
TI  - [Clinical value of dynamic posturography in the evaluation and rehabilitation of
      vestibular function of patients with benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To explore the clinical value of dynamic posturography in the
      evaluation and rehabilitation of vestibular function of patients with benign
      paroxysmal positional vertigo (BPPV). METHODS: A total of 48 patients with BPPV
      of posterior semicircular canal in vertigo clinic of our hospital from May 2007
      to December 2008 were retrospectively analyzed in this study. All patients
      underwent the inspection of caloric test, static posturography, and dynamic
      posturography. The vestibular tests were performed at two different time points:
      at onset when patients had typical nystagmus provoked by the Dix-Hallpike
      maneuver before treatment with the Epley maneuver (canalith repositioning
      maneuver, CRM), and at one week after treatment with CRM as their nystagmus
      disappeared. And results at theses two time points were compared. Eight patients
      whose dynamic balances were still abnormal after CRM accepted vestibular
      rehabilitation exercise using dynamic posturography, and re-examined 3 weeks
      later with dynamic posturography. RESULTS: Among 48 cases of BPPV, the abnormal
      rates of caloric test, static posturography, and dynamic posturography before CRM
      were 25.0%, 33.3% and 70.8%, respectively. The abnormal rate of dynamic
      posturography was much higher than that of caloric test or static posturography,
      and the differences were statistically significant (chi2 = 4.84, 7.88; P < 0.05).
      After CRM, the abnormal rates of caloric test, static posturography, and dynamic
      posturography were 14.6%, 8.3% and 16.7%, respectively. After CRM, the abnormal
      rate of static and dynamic posturography showed significant reduction (chi2 =
      24.04, 10.08; P < 0.05), however, the results of caloric test showed no
      significant change (chi2 = 3.20, P > 0.05). Eight patients whose dynamic balances
      were still abnormal after CRM, accepted vestibular rehabilitation exercise
      lasting 3 weeks using dynamic posturography. The dynamic balances were all
      improved to normal after vestibular rehabilitation. CONCLUSIONS: Dynamic
      posturography can quantitatively analyze postural balance, and is helpful in
      comprehensive evaluation of the vestibular function of BPPV patients. Impaired
      balance often presents in patients with BPPV. Treatment of BPPV using the
      canalith repositioning maneuver results in improved postural stability in static
      and dynamic posturography. However, not all patients have normal dynamic
      stability after successful CRM. The vestibular rehabilitation exercise using
      dynamic posturography is a helpful adjunct to the treatment for these patients.

PMID- 21092671
TI  - [A comparative study on numerical simulation of the normal nasal airflow during
      periodic breathing and steady-state breathing].
AB  - OBJECTIVE: To compare the characteristics of normal nasal airflow during periodic
      breathing and steady-state breathing. METHODS: Fluent software was used to
      simulate the nasal cavity and paranasal sinus structures following CT scanning of
      a normal adult subject. Air flow velocity, pressure, distribution and streamlines
      were calculated and compared during periodic breathing and steady-state
      breathing. RESULTS: The same flux, the performance of nasal airflow on 15.600 s
      of periodic breathing and steady-state expiratory (entrance flow was 697.25 ml/s)
      were as follows: air flow in the common and middle meatus accounted for more than
      50% and 30% of total nasal cavity flow during two respiratory status. Flow
      velocity and pressure of nasal cavity and each paranasal sinus were extremely
      similar. The flow trace during two respiratory status in the inferior and lower
      part of the common meatus were predominately straight in form.Flow were parabolic
      in the middle and superior meatus and the middle and upper parts of the common
      meatus. The flow trace of nasal airflow on 16.495 s of periodic breathing had
      wide areas vortex in nasopharynx and limen nasi, the average speed was 0.0706
      m/s, while the entrance flow 7.62 ml/s stable state of the left nasal expiratory,
      the average speed was 0.0415 m/s, the flow trace was similar to 697.25 ml/s.
      CONCLUSION: The same flow, except in the junction of the respiratory cycle, the
      performance of normal nasal airflow during periodic breathing and steady-state
      breathing were similar.

PMID- 21092672
TI  - [A clinical study of paradoxical breathing during sleep in children].
AB  - OBJECTIVE: Abnormal breathing during sleep included many patterns. In this study,
      we investigated paradoxical breathing patterns during sleep in children using
      standard polysomnography (PSG). METHODS: Children who come to the ENT because of
      snoring were included into the study consecutively. Those who had craniofacial
      anomalies, diabetes, chronic lung diseases, and neuromuscular diseases were
      excluded. At the same time, no sleep snoring children were include as controls.
      Thirty-eight snoring children and twenty-six no snoring children were recruited.
      Polysomnography (PSG) was performed on all subjects. We determined the frequency
      of paradoxical breathing patterns during sleep through blind analysis of
      polysomnograms obtained in all subjects and compared the difference between
      children with snoring and normal controls. RESULTS: The appearance of paradoxical
      breathing was assessed in all subjects. Among children with snoring, the apparent
      amount of paradoxical breathing time and the percent of paradoxical breathing
      time spent in total sleep time (x(-) +/- s) were (70.1 +/- 40.4) min and 17.9% +/
      11.0% respectively. Comparing with control group (28.2 +/- 25.7) min and 7.3% +/
      6.8%, there was obvious difference (paradoxical breathing time t = 5.060,
      percent of paradoxical breathing time t = 4.767, P < 0.05). Thirty-eight snoring
      children were divided into normal-mild group (eighteen children) and moderate
      severe group (twenty children). The children whose PSG results were normal and
      mild had more paradoxical breathing time and the percent of paradoxical breathing
      time than moderate-severe group. The apparent amount of paradoxical breathing
      time of normal-mild group, moderate-severe group and control group were (85.9 +/-
      31.7) min, (55.8 +/- 42.7) min and (28.2 +/- 25.7) min. Among the three groups,
      there was obvious difference (F = 15.897, P < 0.05). The percent of paradoxical
      breathing time of the three groups were 22.0% +/- 10.2%, 14.1% +/- 10.5% and 7.3%
      +/- 6.8% (F = 14.167, P < 0.05). CONCLUSIONS: Currently published
      polysomnographic scoring recommendations overlook some common breathing
      abnormalities during sleep that are associated with clinical complaints.
      Paradoxical breathing is abnormal breathing patterns during sleep and its
      appearance is used to aid in the identification of respiratory events.

PMID- 21092673
TI  - [Neck dissection of Levels II and III for the treatment of supraglottic laryngeal
      cancer with clinically negative neck].
AB  - OBJECTIVE: To evaluate the feasibility of routine inclusion of levels II and III
      in neck dissection to treat the occult neck metastasis as elective treatment for
      supraglottic cancer with clinically node negative (cN0). METHODS: The results of
      52 cN0 patients with supraglottic cancer treated in Tumor Hospital, Harbin
      Medical University from October 2002 to March 2006 were reviewed retrospectively.
      RESULTS: Of the 52 patients with supraglottic cancer and cN0 neck, 32 cases
      received ipsilateral SND (levels II and III) and 20 cases with bilateral SND
      (levels II and III). Fifteen (28.9%) of 52 patients were found to have occult
      regional metastasis on pathological examination. Three patients without
      metastasis in dissected side at pathologic examination showed metastasis in the
      contralateral undissected neck later on therefore the total occult metastasis
      rate was 34.6% (18 of 52). The unilateral and bilateral neck occult metastases
      were determined in 15 cases (28.9%) and 3 cases (5.8%) respectively. A total of
      1190 lymph nodes were harvested in 72 specimens, with 30 positive nodes. The
      distributions of the 30 positive nodes were as follows: level IIA 83.3% (25
      nodes), level III 16.7% (5 nodes). Three-year regional recurrence rate was 5.8%.
      The 3-year survival rate was 84.6% according to Kaplan-Meier in all cN0 patients
      (n = 52). Patients with positive neck metastasis and patients with extracapsular
      spread had higher regional recurrence rates (P = 0.021 and 0.002, respectively).
      CONCLUSIONS: The results support the use of SND (levels II and III) in cN0
      supraglottic cancer. This procedure will reduce both operating time and
      morbidity, without compromising the oncologic result.

PMID- 21092674
TI  - [Effects of RNA interference targeting four different genes on the growth and
      proliferation of nasopharyngeal carcinoma CNE-2Z cells].
AB  - OBJECTIVE: To explore the effects of RNA interference (RNAi) targeting four
      different genes (VEGF, c-myc, survivin, hTERT) on the growth and proliferation of
      nasopharyngeal carcinoma (NPC) CNE-2Z cells. METHODS: Plasmid-1 targeted all four
      genes, plasmid-2, 3, 4 and 5 targeted VEGF, c-myc, survivin and hTERT
      respectively. These plasmids were transfected separately into human NPC CNE-2Z
      cells and xenograft tumors in nude mice. The expressions of plasmids in NPC CNE
      2Z cells and xenograft tumors were observed. Cell proliferation was detected with
      MTT assay. The inhibitory effects on target genes were evaluated with RT-PCR and
      Western blot respectively. The effects of the plasmids on the biological behavior
      of CNE-2Z cells were observed with Transwell invasion chamber model. Apoptosis
      was determined with flow cytometer. The inhibitory effect of the plasmids on
      xenograft tumors were observed in nude mice. RESULTS: CNE-2Z cell proliferation
      was significantly inhibited and in vitro invasion ability was significantly
      decreased in the plasmid-1 group compared with those in the plasmid 2 - 5 groups
      (all P < 0.05). mRNA and protein expressions of all four genes decreased in the
      plasmid-1 group. The apoptosis rate in the plasmid-1 group was higher than that
      in the plasmid 2 - 5 groups (all P < 0.05). Growth of xenograft tumors in nude
      mice were significantly inhibited in the plasmid 1 - 5 groups, particularly in
      the plasmid-1 group. CONCLUSION: RNA interference targeting multiple genes can
      effectively inhibit NPC proliferation and induce apoptosis, which provides an
      experiment basis for NPC gene therapy.

PMID- 21092675
TI  - [Expression and clinical significance of CCR6, CCR7 and CD4(+)CD25(+) Foxp3(+)
      regulatory T cells in laryngeal squamous cell carcinoma and neck lymphatic
      metastasis].
AB  - OBJECTIVE: To evaluate the expressions and clinical significance of chemokine
      receptor 6 (CCR6), chemokine receptor 7(CCR7) and CD4(+)CD25(+)Foxp3(+)
      regulatory T cells (Treg) in laryngeal squamous cell carcinoma (LSCC) and
      metastatic lymph nodes. METHODS: Blood samples and fresh specimens of LSCC were
      obtained from 50 LSCC patients treated. Blood samples from normal subjects were
      donated by 20 volunteers. The mRNA expressions of CCR6, CCR7 and their ligands
      CCL20, CCL19/CCL21 were detected by real-time quantitative RT-PCR. Expressions of
      CCR6 and CCR7 proteins were examined with immunohistochemistry. Flow cytometry
      was used to investigate Treg in peripheral blood mononuclear cells. RESULTS: The
      relative expression levels of CCR6, CCR7 and CCL19 mRNA in tumor tissues with
      lymphatic metastases were significantly lower than those without lymph node
      metastases (P < 0.05), while the relative expression level of CCL20 mRNA in tumor
      tissues with lymphatic metastases was significantly higher than that of those
      without metastatic lymph nodes (t = 2.39, P < 0.05). Immunohistochemistry showed
      that the expression levels of CCR6 and CCR7 in tumor tissues in patients with
      lymph node metastases than those without lymph node metastases. CCR6 and CCR7
      expressions were also detected in metastatic lymph nodes. Flow cytometry showed
      that the percentage of Treg in blood in LSCC patients was significantly higher
      than that in normal subjects (t = 2.19, P < 0.05), and those with lymph node
      metastasis had a much higher percentage of Treg (t = 2.14, P < 0.05).
      CONCLUSIONS: CCR6, CCR7 and Treg could take part in the process of lymph node
      metastasis in LSCC patients.

PMID- 21092676
TI  - [Inhibition of cell growth by rapamycin through targeting mammalian target of
      rapamycin signaling pathway in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To study the effects of rapamycin on cell growth and cell cycle in CNE
      1 and CNE-2 cells. METHODS: Growth inhibition effect of rapamycin on CNE-1 and
      CNE-2 cells were assessed by cell counting kit-8 (CCK-8) assay. Morphological
      alterations of the cells were observed by microscope. Cell cycle and cell
      apoptosis were analyzed by FCM. The expression of mammalian target of rapamycin
      (mTOR) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: The growth of CNE-1 and CNE-2 cells was inhibited significantly by
      rapamycin dose-dependently. FCM showed that CNE-1 and CNE-2 cells at 48 hours
      after rapamycin (150 nmol/L) treatment were arrested in the G0/G1 phase of cell
      cycle. However rapamycin treatment did not significantly induce apoptosis of CNE
      1 and CNE-2 cells (P > 0.05). RT-PCR showed that rapamycin significantly
      inhibited mRNA expression of mTOR in CNE-2 cells (t = 10.625, P < 0.01).
      CONCLUSIONS: Rapamycin inhibits the growth of CNE-1 and CNE-2 cells by inhibiting
      the progression of cell cycle, which could be achieved through decreasing the
      expression of mTOR.

PMID- 21092677
TI  - [Prevention and treatment of cerebrospinal rhinorrhea in postradiotherapy sinus
      surgery].

PMID- 21092678
TI  - [Endoscopic operation for cerebrospinal fluid rhinorrhea by bath-plug method:
      three cases report].

PMID- 21092679
TI  - [Report of a case with long time persisted esophagus foreign associated with
      hoarse].

PMID- 21092680
TI  - [A case of ectopic thyroid adenoma at the lateral neck and the lingual base
      accompanying with motor neuron disease].

PMID- 21092681
TI  - [Angiomyofibroblastoma of auricle: report of a case].

PMID- 21092682
TI  - [Intravascular stent therapy for cerebral venous sinus tinnitus].

PMID- 21092683
TI  - [Laryngocele of lateral neck: one case report].

PMID- 21092684
TI  - [Castleman's disease of the neck: a case report].

PMID- 21092685
TI  - [Summary of 2010 Chinese speech audiometry workshop].

PMID- 21092686
TI  - [Diagnostic significance of vestibular evoked myogenic potentials and subjective
      visual vertical examinations in the inner ear malformations].

PMID- 21092687
TI  - [Phonomicrosurgery].

PMID- 21092688
TI  - [Summary of the 29th annual conference of European association of allergy and
      clinical immunology].

PMID- 21092689
TI  - [Asymmetric dimethylarginine (ADMA) in children with diabetes type 1].
AB  - INTRODUCTION: Asymmetric dimethylarginine (ADMA), a naturally occurring product
      of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial
      nitric oxide synthase. ADMA is now recognized as an independent marker of
      endothelial dysfunction and atherosclerosis. Data concerning ADMA level in type 1
      diabetes (DM1) are controversial. The aim of the study was to evaluate ADMA level
      in children with DM1, without clinical evidence of vascular complications, with
      particular attention to additional cardiovascular risk factors (hypertension,
      obesity, hyperlipidemia). MATERIAL AND METHODS: The study group included 72
      children with DM1, aged mean 15+/-3 yrs (8-20 yrs), 33 boys and 39 girls, with
      diabetes duration time mean 6.6+/-3.5 yrs (1-14 yrs), HBA1c mean level 8.2+/-2.3%
      (5.6-15%). The control group consisted of 41 (19 boys and 22 girls) healthy
      children, aged mean--14.8+/-2.6 yrs, from 8 to 18 yrs, gender matched, with no
      family history of cardiovascular disease. ADMA level was determined in plasma
      using ELISA kit (DLD Diagnostica, Hamburg, Germany) RESULTS: ADMA level was
      similar in children with diabetes and in the control group: 0.69+/-0.33 vs. 0.7+/
      0.27 MUmol/L, ns. We did not find differences in ADMA level in diabetic children
      with the presence of additional diseases being cardiovascular risk factors. In
      the group of 13 children with hypertension ADMA level was the highest: 0.79+/
      0.25 MUmol/L, but the difference was statistically insignificant in comparison to
      children with diabetes without hypertension and in comparison to healthy
      controls. CONCLUSIONS: Children with DM1, without clinically evident vascular
      complications, have ADMA levels similar to healthy children. A possible
      relationship between ADMA and hypertension in these patients requires further
      investigation.

PMID- 21092690
TI  - [The frequency of structural abnormalities in the hypothalamo-pituitary region
      and their clinical significance in patients with growth hormone deficiency].
AB  - INTRODUCTION: In children with confirmed growth hormone deficiency (GHD) the most
      common diagnosis is idiopathic isolated GHD. Nevertheless, it cannot be ignored,
      that the GHD might also be caused by structural malformations or tumours in
      hypothalamo-pituitary region. The aim of the study was to evaluate the frequency
      of structural malformations in the hypothalamo-pituitary region in children with
      growth hormone deficiency and its correlation with clinical parameters. MATERIAL
      AND METHODS: 99 patients with growth hormone deficiency were examined (30 girls
      and 69 boys). Mean age of the patients was 10+/-3.4 years. The diagnosis of
      growth hormone deficiency was based on standard criteria: growth hormone level
      below 10 ng/ml in two stimulatory tests and auxological data. Magnetic resonance
      imaging was performed in pituitary protocol: (SE, TSE in T1- and T2-weighted
      pictures). Patients were divided into two groups: with malformations (ZM) of
      hypothalamo-pituitary region and without the malformations (BM). In the course of
      analysis, the ZM group was divided into the following subgroups: with a severe
      malformation (Mw) and with mild malformations (Mmn). The results of growth
      hormone stimulatory tests, IGF-1 level, additional hormonal disorders and
      auxological parameters were compared between the groups. RESULTS: In the examined
      group structural malformations of hypothalamo-pituitary region were found in 42%
      (n=42) of patients. The most common finding was pituitary hypoplasia and ectopy
      of the posterior lobe. The groups did not differ by age, mean height deficiency
      (in SDS) and mean height of parents. The mean IGF-1 level was statistically
      significantly lower in ZM group than in BM group (p <0.04). Similarly the maximal
      growth hormone secretion in stimulatory tests was lower in ZM patients. The age
      of diagnosis was statistically significantly younger in the Mw subgroup, and
      multihormonal hypopituitarism was diagnosed only in patients with a severe
      structural malformation of hypothalamo-pituitary region. CONCLUSIONS: 1. The
      structural malformations of hypothalamo-pituitary region were found in 42% of
      patients. 2. The diagnosis of multihormonal hypopituitarism in a patient is
      connected with an increased risk of the presence of severe structural
      abnormalities in hypothalamo-pituitary region. 3. IGF-1 level and maximal GH
      secretion are negatively correlated with the presence of malformations of the
      hypothalamo-pituitary region.

PMID- 21092691
TI  - [Low birth weight--additional important factor of diagnosis in children with
      short stature].
AB  - INTRODUCTION: Birth parameters are one of the more important predictors of body
      height in adult life. Children with low birth weight (LBW) are an essential and
      heterogenic group of patients diagnosed because of short stature. AIM OF THE
      STUDY: Evaluation of frequency of low birth mass in children with short stature
      and evaluation of anthropometric parameters in children with low and normal birth
      weight. MATERIAL AND METHODS: Analysis of birth data and present somatic
      parameters in 802 children with short stature who were admitted to the Clinic of
      Paediatrics and Endocrinology. This group consisted of 456 boys and 346 girls.
      The mean calendar age was 9 years. Differential diagnosis of growth disorders was
      made. Our group contained 133 children with growth hormone deficiency (GHD) and
      26 girls with Turner's syndrome. Data of birth parameters (length, weight and
      length of pregnancy) were collected, anthropometric measurements of children and
      their parents were made, body mass index (BMI) was calculated. Low birth weight
      (LBW) is a birth weight <=2500 g. The values of present somatic parameters were
      normalized according to the references of the Institute of Mother and Child, data
      of parameters were given in standard deviation score. RESULTS: In the whole
      examined group LBW was observed in 17.3% (137 children). LBW was observed in 23%
      of girls with Turner's syndrome. Among the children who were born on time low
      birth weight was observed in 5.3% (30 children--15 boys and 15 girls). In this
      group there were 10 patients from a twin pregnancy, 2 with fetal alcohol syndrome
      and 4 with Silver-Russell syndrome. In 14 patients SGA (small for gestational
      age) was observed. The children with LBW contacted the clinic a year earlier than
      other patients, with more body height deficiency (-2.5 SDS vs. -2.1 SDS) and
      smaller values of BMI. No statistically significant differences between
      midparental height in both groups were observed. CONCLUSION: 1. Low birth weight
      is diagnosed in every sixth child with short stature in the Clinic of
      Endocrinology. 2. Children born on time with low birth weight should be diagnosed
      early towards congenital genetic disorders and development defects.

PMID- 21092692
TI  - [Frequency of hypotrophic births in the Warsaw population].
AB  - INTRODUCTION: Newborn's reduced body mass and length are regarded as an important
      symptom. The diagnosis requires careful observation of the individual's course of
      growth and metabolic condition. Various criteria are used to diagnose hypotrophy;
      3rd, 5th or 10th percentile body mass are the most common, although others
      recommend using a value of -2.0 SDS body mass and length. AIM OF THE STUDY: To
      define the frequency of body mass and length deficiency in newborns in the Warsaw
      population. MATERIAL AND METHODS: 4096 children born in single deliveries in 2009
      at one Warsaw hospital. Body dimensions at birth were compared against the
      following standards, taking gestation period and sex into consideration: 1. Usher
      and McLean (UML). 2. A standard generally used in Warsaw maternity wards, drawn
      up by the Mother and Baby Institute (IMiD). 3. A standard drawn up in
      Wielkopolska (WLKP). Hypotrophy was diagnosed retrospectively on the basis of 
      2.0 SDS body mass and/or body length and 10th percentile body mass criterion.
      RESULTS: Regardless of sex and the standard being applied, at least one of the
      analysed body dimensions fell at or below -2.0 SDS in approximately 1% of all
      children. In newborn boys hypotrophy was diagnosed significantly less frequently
      using the UML standard than using the national ones, while in newborn girls it
      was diagnosed less frequently using the IMiD standard than UML or WLKP. Birth
      mass below the 10th percentile was found in approximately 7% and in just over 3%
      of all newborns using the IMiD and WLKP standards respectively. CONCLUSIONS: The
      absence of national standards for body length at birth makes the -2.0 SDS
      criterion difficult to use, while basing the diagnosis purely on evaluating body
      mass results in too few diagnoses of hypotrophy. Using the 10th percentile
      criterion allows for diagnosing hypotrophy in a few percent of newborns, while
      the Warsaw and Wielkopolska standards result in more diagnoses. Taking population
      trends into account, we postulate the need to prepare new national standards of
      body dimensions of newborns based on the gestation period.

PMID- 21092693
TI  - [Retrospective assessment of growth monitoring of subjects born between 1989
      1991].
AB  - INTRODUCTION: Systematically taken measurements of body length, and--after 18
      months of life--height, facilitate the correct monitoring of the course of
      physical development in children and teenagers. Measuring body mass only is
      incorrect and may lead to a faulty evaluation of the patient's condition. AIM OF
      STUDY: Assessment of frequency of measurements of body mass and height during the
      developmental period among students born between 1989-1991. MATERIAL AND METHODS:
      For 109 subjects (52% women), age 20.0+/-1.0 year, range 19.1-23.8 years of age,
      measurements at birth, duration of the mother's pregnancy and frequency of
      measurements of body mass and weight until the 18th year of life. RESULTS: The
      frequency of measurements of body length and height was the highest during the
      1st and 2nd year of life, on average every 3 months during the 1st year and every
      6 months during the 2nd year. However, during the 1st year as many as 1/3 of
      children were assessed incorrectly by having only their body mass measured.
      During the 2nd year, regardless of body mass at birth, measurements were taken
      more frequently than during the 1st year, which may suggest inadequate
      preparation of the medical personnel to take measurements of the baby's body
      length. Measurements of body height and even body mass during puberty and the
      growth spurt were carried out in a far too small percentage of subjects.
      CONCLUSIONS: 1. Body mass measurements are all too frequently not accompanied by
      measurements of body length or height, with the result that the physician is
      unable to assess the child's growth pattern. 2. Measurements of body height and
      mass were taken too infrequently during childhood and puberty, which in many
      cases makes it impossible to assess the subject's physical development.

PMID- 21092694
TI  - [Incidence of low birth weight in academic youth].
AB  - INTRODUCTION: Birth parameters are used to evaluate infant's maturity and to
      indicate children with a potential risk of growing disorders and metabolic
      complications in later life. Low birth weight can be connected with higher fat
      content, especially in the abdominal part in adult individuals. Low birth weight
      is recognized as one of the criteria of metabolic syndrome in non-obese
      individuals. AIM OF THE STUDY: The percentage of academic youth aged 19-25 years
      born with low birth weight was evaluated. MATERIAL AND METHODS: 146 students (52%
      women and 48% men) of Warsaw higher schools took part in the study. Data of birth
      parameters and gestational age (GA, weeks) were gained from the medical
      documentation retrospectively. Infant's mass <=2999 g was recognized as decreased
      birth weight (LBW group). Body height and body mass, waist and hip circumferences
      were measured. WHR was calculated as well. Bioimpedance method was used to
      evaluate the body composition, height and weight were standardized using data for
      18-year-old women and men from Warsaw population. RESULTS: Decreased birth weight
      has been identified in 18% studied population - LBW group: 65% women and 35% men.
      It has been shown that students with low birth weight were characterized by a
      significantly lower body height (-0.22+/-1.14 v. 0.38+/-1.02 SDS) and body mass (
      0.11+/-1.15 vs. 0.70+/-1.15 SDS) in comparison with individuals born with normal
      birth parameters. Body fat content in students of studied groups was similar. It
      has been noted that WHR index was significantly lower (p=0.0009) in men of LBW
      group than in those of NBW group. CONCLUSIONS: 1. Decreased birth weight appears
      more frequently among girls. It's suggested that MONW are more common in females.
      2. The relationship between birth parameters and height and weight in adults was
      confirmed. 3. In young men distribution of body fat is associated with birth
      weight.

PMID- 21092695
TI  - [Assessment of physical fitness in children and teenagers with type 1 diabetes].
AB  - INTRODUCTION: Physical activity is regarded as one of the four basic factors
      influencing the concentration of glucose in the blood of diabetic patients.
      Despite this, concerns about hypoglycaemia and exposure of chronically ill
      children to excessive fatigue mean that their physical activity is frequently
      inadequate. Until now, physical endurance of diabetes mellitus patients has been
      assessed more frequently than their physical fitness. AIM OF THE STUDY: An
      attempt to assess physical fitness of a group of children and teenagers suffering
      from type 1 diabetes (DM1). MATERIALS AND METHODS: Physical fitness was assessed
      in 40 children with DM1: mean age for girls (n=20) was 10.58+/-2.63 years old
      (7.03-16.11), and for boys (n=20) 12.25+/-2.62 years old (7.23-16.52). Physical
      fitness was assessed on the basis of the result of 8 out of 9 tests from the
      European test of physical fitness (Eurofit) set. The results of individual trials
      were expressed as percentile measurements read against percentile grids designed
      by Stupnicki, Przeweda and Milde. RESULTS: When compared against healthy peers,
      girls with DM1 achieved significantly lower scores in balance maintenance, long
      jump and hand grip tests. Boys with DM1 were fitter than girls with DM1 in tests
      assessing balance, hand grip and agility, yet they were less fit than their
      healthy peers in balance and hand grip tests. CONCLUSIONS: Physical fitness of
      children and teenagers suffering from DM1 differs between the sexes. In boys it
      was assessed as being close to that of their healthy peers, while in girls it was
      assessed as being inadequate. It is likely that the girls' poorer physical
      fitness results from both their state of health and environmental conditions,
      which were not defined in this study. It seems that diabetic girls should be
      especially encouraged to take part in regular physical exercise, since it is
      regarded as one of the key components of correct therapeutic procedures in
      diabetes.

PMID- 21092696
TI  - [Physical activity for young adults born with low body weight on the background
      of peers].
AB  - INTRODUCTION: Low birth parameters are associated with an increased risk of
      insulin resistance, type 2 diabetes, glucose intolerance and hypertension at
      later life. Regular physical activity can counteract these metabolic disorders.
      THE AIM OF THE STUDY: We determined the relation of the declared physical
      activity and body composition in young adults with respect to their birth weight.
      MATERIAL: A total of 156 subjects (52% women and 48% men) took part in the study
      (the average age 20.6+/-1.2 years). Participants who declared regular physical
      activity (minimum 3 times per week) were included in group I (n=66), others in
      group II (n=99). In each group, the percentage of people with small (SBW) and
      normal (NBW) birth weight was assessed. METHODS: Information about birth
      parameters and duration of pregnancy was obtained from medical records. Infant's
      mass <=2999 g was recognized as small birth weight. Body height, body weight,
      waist and hips circumferences and body composition by BIA were measured.
      Frequency of physical activity was determined during an interview. RESULTS:
      Percentage of participants with small birth weight was respectively 17% in group
      I and 21% in group II. In group I standardized body height was significantly
      lower in subjects with SBW in comparison with those with NBW. Participants from
      group II with SBW had markedly lower standardized body weight and standardized
      BMI than adults with NBW. Independently of birth weight physically active persons
      characterized higher WHR values than their non active counterparts. Body fat
      content was significantly lower in group I (both in participants with SBW and
      NBW). Women and men from group I with SBW had also higher fat free mass in
      comparison with those from group II. CONCLUSIONS: Body fat content in young
      adults with small birth weight is related to their physical activity. People who
      regularly exercise had lower fat mass in comparison with non exercising ones.
      This is the confirmation of a protective influence of physical activity.

PMID- 21092697
TI  - [Assessment of anaerobic capacity for subjects with short, normal and tall
      stature between 18-23 years of age].
AB  - INTRODUCTION: Until now it has not been established whether anaerobic capacity of
      subjects with short stature, statistically comprising 10% of the population,
      differs from those of normal and tall stature (> 90 centile). No results of
      studies comparing anaerobic capacity for subjects with a range of body heights
      have been published in literature. MATERIAL AND METHODS: 435 (women 57%, men 43%)
      healthy young adults ranging between 18-23 years of age. Physical parameters for
      anaerobic capacity (work, maximum generated power and duration) have been marked
      during a 10-second exercise burst carried out on a cycloergometer. Subjects were
      classified into three body height categories: < 10 centile (ct)--short stature;
      between 10-90 ct--normal stature; > 90 ct--tall stature. RESULTS: Short stature
      was noted in 5% subjects, with a height deficiency (<= -2.0 SDS) noted in 0.7%
      subjects. Tall stature was noted among 22% subjects. In both sexes the cohort
      included a significantly greater than expected (p < 0.001) number of tall
      statured subjects and a significantly lower number (p < 0.01) of short-statured
      subjects. No differences were found in the mean parameters of anaerobic capacity
      for subjects of short, normal and tall stature, with the exception of women of
      tall stature whose results were significantly better than those for women of
      normal stature. CONCLUSIONS: No significant differences were found in the
      capacities of subjects with short, normal and tall stature. However, with regard
      to women, in particular those of tall stature, a correlation between body height
      and anaerobic capacity was observed. It must be noted that the majority of the
      worst results were noted among the short-statured subjects, indicating that
      caution must be taken during interpretation of anaerobic capacity levels among
      this population. In order to correctly interpret results of anaerobic capacity
      studies, a standard needs to be put in place for the national population taking
      into regard sex and age, while for people of short stature the causes of their
      short stature must be established.

PMID- 21092698
TI  - [Posture in Turner syndrome patients].
AB  - INTRODUCTION: Turner syndrome (TS) is a chromosomal disease regarded as the most
      common cause of pathological short stature in women. TS patients frequently
      present with abnormalities in the structure of the vertebrae and limb bones,
      leading to this assessment of posture in girls and women with TS. AIM OF THE
      STUDY: Assessment of posture in TS patients. MATERIALS AND METHODS: Posture was
      assessed in 63 TS patients ranging between 6-27 years of age. All patients under
      16 years of age were undergoing treatment with recombinant human growth hormone.
      The older patients had received the treatment in the past and were undergoing
      oestrogen or combined oestrogen and progesterone treatment. The TS diagnosis was
      confirmed in each case by a cytogenetic study. Two methods of posture assessment
      were used: Moire's photogrammetric (in 68% patients) or an orthopaedic
      examination (in 32% of patients). Posture was assessed in the median and frontal
      planes. RESULTS: The photogrammetric assessment in the median plane found normal
      posture among 30% of patients, 33% of patients exhibited lordosis, while 28% of
      patients exhibited kyphosis. Orthopaedic examination in the medial plane found
      normal posture among half of patients under 16 years of age, while all the older
      patients (n=4) exhibited faulty posture. Clinical examination found more cases of
      kyphosis than other posture defects. In the frontal plane over half of all
      patients were found to have scoliosis, irrespective of patient's age or method
      used. CONCLUSIONS: Because of the numerous and diverse posture defects found in
      the studied patients, routine assessment of posture in all TS patients is
      recommended. From the clinical perspective it seems that a single method of
      posture assessment in TS patients is recommended to simplify comparison of
      assessment results and improve understanding of the frequency of incidence of
      individual posture defects in TS patients.

PMID- 21092699
TI  - [Perception manner of the father of an obese child].
AB  - INTRODUCTION: The child's representation in the father is understood as an
      experience manner of itself. There are specific relation properties of the father
      to the obese child. AIM OF THE STUDY: The aim of this article is an attempt to
      explain/find out what is a mental representation of a child experienced by
      fathers of obese girls and boys. MATERIAL AND METHODS: 30 fathers were
      investigated: 15 fathers of obese children (8 girls and 7 boys) and 15 fathers of
      children with normal body mass (8 girls and 7 boys). The mean age of the obese
      children of the investigated fathers was 8.23, and for normal body mass children
      of the investigated fathers it was 8.47. All fathers were investigated by a
      clinical interview with 15 questions concerning a mental child's representation.
      The obtained results were analyzed in relation to: 1. the contents of a mental
      father's representation of the child: cognitive, emotional, social, sexual,
      certificate, behavioral and somatic. 2. Access to a mental father's
      representation of the child. 3. Differentiation of a mental father's
      representation of the child. 4. Continuity of a mental father's representation of
      the child. RESULTS: 1. There are differences in a mental child's representation
      in fathers of obese and of normal body mass children. There are also differences
      in a mental child's representation in fathers of obese girls and boys 2. Fathers
      of obese children more often than the fathers of children with the normal body
      mass identify with the external contents of a mental child's representation.
      CONCLUSION: 1. A mental representation of an obese child in the father often
      contains external, not mental properties. 2. The representation of an obese child
      in the father contains deficit of mental properties. 3. Specific difficulties in
      the experience of a mental representation of an obese child in the father like
      f.e. emotional emptiness or dependence were pointed out.

PMID- 21092700
TI  - The influence of vegan diet on bone mineral density and biochemical bone turnover
      markers.
AB  - INTRODUCTION: Vegetarian diets can be healthy when they are well balanced and if
      a variety of foods is consumed. However, elimination of animal products from the
      diet (vegan diets) decreases the intake of some essential nutrients and may
      influence the bone metabolism. This is especially important in childhood and
      adolescence, when growth and bone turnover are most intensive. The aim of the
      study was to assess the effect of vegan diet on bone density (BMD) density and
      serum concentrations of bone metabolism markers. MATERIAL AND METHODS: We
      examined a family on vegan diet which consisted of parents and two children.
      Dietary constituents were analysed using a nutritional program. Total and
      regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of
      calcium and phosphate in serum obtained from fasting patients were determined by
      colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and
      bone turnover markers by specific enzyme immunoassays. RESULTS: In studied
      vegans, the dietary intake of phosphate was adequate while calcium and vitamin D
      were below the recommended range. Concentrations of calcium, phosphate and bone
      turnover markers in the serum of all subjects were within the physiological
      range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was
      between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0).
      Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to 
      1.7 in children. CONCLUSIONS: Our results suggest that an inadequate dietary
      intake of calcium and vitamin D may impair the bone turnover rate and cause a
      decrease in bone mineral density in vegans. The parameters of bone density and
      bone metabolism should be monitored in vegans, especially children, in order to
      prevent bone abnormalities.

PMID- 21092701
TI  - [Insulin receptor defect as a cause of Rabson-Mendenhall syndrome and other rare
      genetic insulin resistance syndromes].
AB  - Insulin plays a very important role in maintaining homeostasis of the whole
      organism. It regulates glucose metabolism, glycogen synthesis, lipid and protein
      metabolism. Insulin receptors are present in virtually all cells, which is
      reflected by the diversity of regulatory processes in which this hormone is
      involved. Any dysfunction of insulin signalling pathway as a result of insulin
      receptor gene mutations is linked with various forms of insulin resistance,
      including insulin resistance type A, Donohue or Rabson-Mendenhall syndrome, which
      differ in the level of severity. Molecular analysis of insulin receptor gene may
      lead to a better understanding of molecular mechanisms underlying various types
      of insulin resistance and help to develop a more efficient treatment. They may
      also be used as a powerful tool in prenatal diagnostics as well as in pregnancy
      planning.

PMID- 21092702
TI  - [Progress in diagnostics and therapy of type 1 and type 2 diabetes--part 2].
AB  - The report is the second part of a former publication. The authors presented a
      series of reports, especially from the last year, concerned with diagnostics and
      therapy of type 1 and type 2 diabetes. The progress of the diagnostics included
      especially new, more perfect glycaemic monitoring systems. The progress and
      future of the therapy with personal insulin pumps and different international
      recommendations for the therapy of type 1 diabetes with short-acting insulin
      analogues were presented. Also, the problem of the reports about the increased
      risk of cancer after the treatment with a long-acting insulin analogue glargine
      was discussed (Lantus). Further investigations of the effect of the therapy with
      a biphasic insulin and new possibilities of oral therapy in type 2 diabetes were
      mentioned. It was stressed that actually, a lot of proposals of new drugs and new
      reports are observed. These reports are, however, frequently conference news and
      not complete reports and the proposals require further examinations and
      observations for a confirmed appreciation of their efficacy and safety.

PMID- 21092703
TI  - [Psychological factors during pregnancy correlated with infant low birth weigh].
AB  - INTRODUCTION: Contemporary researches state that the child's mental development
      depends on the quality of its relations with mother starting from pregnancy. They
      point to those elements of maternal functioning which decide about the child
      functioning in various dimensions and play a role in the mother-child
      interaction. One of them is emotional state of the mother during pregnancy. THE
      AIM OF THE STUDY: To demonstrate psychological factors which are correlated with
      infant low birth weight. RESULTS: Contemporary researches state that the infant
      low birth weight depends on the mother's mood during pregnancy. Women, frequently
      suffering from negative emotions, who experience high level of anxiety and
      depression, influence the infant's biological development (e.g. infant low birth
      weight) and shape features of its temperament (level of arousal, low level of
      activity, discontentedness, erethism). As a result, the born infant is not only
      smaller and less active but it is also difficult to take care of it. It often
      cries, the mother cannot calm it down, which is the reason for disregulation of a
      mother-infant relationship CONCLUSIONS: Maternal negative emotions experienced
      during pregnancy are related to the risk of pathological changes in the foetus.
      Depressive disorder and high level of anxiety are an indication for psychotherapy
      of the pregnant women. Psychological intervention can prevent from disturbances
      of infant's development and the mother-infant relation.

PMID- 21092704
TI  - [Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus-
      a case report].
AB  - The relation between type 1 diabetes mellitus and autoimmune thyroid diseases is
      well known. In the pathogenesis of both diseases, chronic autoimmunization plays
      an essential role. Specific autoantibodies are also responsible for the onset of
      idiopathic thrombocytopenic purpura. In the paper we present a case of an 11-year
      old girl with insulin dependent diabetes in whom the idiopathic thrombocytopenic
      purpura without bleeding diathesis has been newly diagnosed. The patient had
      positive titres of thyroid autoantibodies, whilst she did not suffer from thyroid
      dysfunction. Due to inefficiency of intravenous gammaglobulins the patient was
      treated with a steroid therapy, which elevated the platelet counts to safe
      levels. However, the episodes of hyperglycemia have appeared as a side effect.
      The insulin therapy was modified and the girl was released in a good condition.
      In this case report, consideration should be given to the wide range of
      autoimmune diseases that can accompany type one diabetes mellitus--not only can
      we observe immune diabetic markers, but also thyroid autoantibodies and anti
      platelet antibodies. Particular therapeutic dilemmas resulting in a difficult
      decision on steroid therapy while treating a diabetic patient with idiopathic
      thrombocytopenic purpura are also presented.

PMID- 21092705
TI  - Quercetin ameliorates experimental autoimmune myocarditis in rats.
AB  - PURPOSE: Experimental autoimmune myocarditis (EAM) in rats is an animal model of
      human giant cell myocarditis and post-myocarditis dilated cardiomyopathy. The
      pathogenesis of EAM has not been elucidated, but there is accumulating evidence
      that cytokines secreted from monocytes/macrophages and T cells play a crucial
      role in the induction and progression of disease. Flavonoids are a large group of
      polyphenolic compounds abundantly present in the human diet, which scavenge
      oxygen radicals and have anti-inflammatory activities. Having in mind in vivo
      beneficial effects of flavonoid quercetin in different animal models of
      immunoinflammatory diseases such as experimental autoimmune encephalomyelitis and
      adjuvant arthritis, on the one side, and its in vitro suppressive effect on
      production of tumor necrosis factor-alpha (TNF-alpha) on the other side, we
      investigated the effects of quercetin on EAM in rats. METHODS: Myocarditis was
      induced in Dark Agouti (DA) rats by injection of porcine cardiac myosin and
      quercetin at doses of 10 or 20 mg/kg was orally administered from days 0 to 21
      after induction of disease. The severity of myocarditis was evaluated by
      determination of heart weight/body weight ratio (Hw/Bw) and histopathological
      examination of hearts. The levels of cytokines (TNF-alpha, IL-12, IL-17 and IL
      10) in serum and lymph node cells (LNC) culture supernatants were measured by
      ELISA. RESULTS: The rats treated with 20 mg/kg of quercetin had significantly
      decreased incidence of EAM, Hw/Bw, macroscopic and microscopic scores of hearts.
      Further, in EAM rats treated with quercetin levels of TNF-alpha and IL-17 were
      significantly lower, while the level of IL-10 was significantly higher both in
      serum and culture supernatants of LNC stimulated with concanavalin A compared
      with vehicle-treated animals. CONCLUSIONS: The present study suggests that
      quercetin ameliorates EAM, at least in part, by interfering production of
      proinflammatory (TNF-alpha and IL-17) and/or anti-inflammatory (IL-10) cytokines.

PMID- 21092706
TI  - Cationic solid lipid nanoparticles loaded by cysteine proteinase genes as a novel
      anti-leishmaniasis DNA vaccine delivery system: characterization and in vitro
      evaluations.
AB  - PURPOSE: Leishmaniasis is a major health problem in many tropical and sub
      tropical countries and development of a safe and easily-available vaccine has
      high priority. Although several antigens potentially capable of inducing
      protective immunity have been studied, in the absence of pharmaceutical industry
      interest they have remained as fine publications only. Amongst them, Cathepsin L
      like cysteine proteinases (CPs) have received considerable attention and type I
      and II CPs have been used in a heterologous prime-boost vaccination regime for
      experimental visceral leishmaniasis in dogs. Due to the promising results of the
      mentioned vaccination regime, we aimed to evaluate cationic solid lipid
      nanoparticles (cSLNs) for in vitro delivery of cpa, cpb and cpb(CTE) intended to
      be used as a cocktail DNA vaccine in our forthcoming studies. METHODS: cSLNs were
      formulated of cetyl palmitate, cholesterol, DOTAP and Tween 80 via melt
      emulsification method followed by high shear homogenization. Different
      formulations were prepared by anchoring pDNAs on the surface of cSLNs via charge
      interaction. The formulations were characterized according to their size and zeta
      potential as well as pDNA integrity and stability against DNase I treatment.
      Lipoplexes' cytotoxicity was investigated on COS-7 cells by MTT test. The effect
      of the DOTAP:pDNA ratio on protection ability and cytotoxicity was also studied.
      In vitro transfection efficiency was qualified by fluorescent microscopy and
      quantified using flow cytometry technique. RESULTS: cSLN-pDNA complexes were
      formulated with suitable size and zeta potential. Efficiency/cytotoxicity ratio
      of cSLN-pDNAs formulations was comparable to linear PEI-25KD-pDNAs polyplexes
      while exhibiting significantly lower cytotoxicity. CONCLUSION: Tested
      formulations were able to deliver immunogenic CP genes efficiently. This data
      proves the ability of this system as a promising DNA vaccine carrier for
      leishmaniasis to cover the main drawback of naked pDNA delivery that is rapid
      elimination from the circulation.

PMID- 21092707
TI  - yCD/HPyCD mixtures as solubilizer: solid-state characterization and sample
      dexamethasone eye drop suspension.
AB  - PURPOSE: Study the complexation of dexamethasone in combinations of gamma
      cyclodextrin (gammaCD) and 2-hydroxypropyl-gamma-cyclodextrin (HPgammaCD) with
      emphasis on solid characterization and development of aqueous dexamethasone eye
      drop suspension for drug delivery through sclera. METHODS:
      Dexamethasone/cyclodextrin (dexamethasone/CD) solid complex systems were prepared
      and characterized by Fourier transform infrared spectroscopy (FT-IR),
      differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and by in
      vitro drug dissolution testing. Sample eye drop suspensions were prepared
      applying solubilizer/suspender consisting of gammaCD/HPgammaCD mixtures,
      poloxamer 407 (P407) and polyvinylpyrrolidone. The eye drop suspension was
      characterized by its physicochemical properties. RESULTS: The solid
      characterization techniques applied suggested that solid complexes were being
      formed. The results indicated that dexamethasone formed non-inclusion or micelle
      like aggregates with HPgammaCD and the gammaCD/HPgammaCD mixture. The dissolution
      and dexamethasone release from the solid dexamethasone/gammaCD/HPgammaCD
      complexes was much faster than from the solid dexamethasone/gammaCD and
      dexamethasone/HPgammaCD complexes. The diameter of the solid particles in the
      dexamethasone eye drop suspension formulations were in all cases less than 10 MUm
      with a mean diameter from 2.5 to 5.8 MUm. The particle size decreased with
      increasing amount of P407. Permeation studies through semipermeable membrane and
      porcine sclera showed that increasing the amount HPgammaCD could enhance drug
      transport through the membrane barriers and this was related to enhanced drug
      solubility. The permeation rates were, however, decreased compared to formulation
      containing gammaCD alone due to larger hydrodynamic diameter of
      dexamethasone/gammaCD/HPgammaCD complex aggregates. All formulations were both
      chemically stable for at least 8 months at 25 degrees C and 40 degrees C.
      CONCLUSIONS: Combination of gammaCD and HPgammaCD, i.e., formation of
      dexamethasone/gammaCD/HPgammaCD complexes, resulted in synergistic effect. That
      is the mixture had greater solubilizing effect than the individual CD, resulted
      in enhanced dissolution and drug delivery through membranes. Furthermore, it is
      possible to control the drug release rate by adjusting the gammaCD:HPgammaCD
      ratio in the solid dexamethasone/gammaCD/HPgammaCD complexes.

PMID- 21092708
TI  - Chondroitin sulfate capsule system for efficient and secure gene delivery.
AB  - PURPOSE: In this study, we developed various ternary complexes of encapsulated
      polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their
      universal usefulness for gene delivery. METHODS: To prepare the cationic
      complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine,
      poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride
      (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE)
      liposomes. CS was added to the cationic complexes for constructions of ternary
      complexes. We examined in vitro transfection efficiency, cytotoxicity,
      hematotoxicity, and in vivo transfection efficiency of the ternary complexes.
      RESULT: The cationic polymers and cationic liposomes bound to pDNA and formed
      stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes
      showed high transgene efficiency in B16-F10 cells; however, they also had high
      cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the
      polyplexes and lipoplexes and form stable anionic particles without disrupting
      their structures. The ternary complexes encapsulated by CS showed high transgene
      efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the
      result of animal experiments, the polyplexes had little transgene efficiency
      after intravenous administration in mice, whereas polyplexes encapsulated by CS
      showed specifically high transgene efficiency in the spleen. The capsulation of
      CS, however, reduced the high transgene efficiency of the lipoplexes. CONCLUSION:
      These results indicate that CS can contribute to polyplex-mediated gene delivery
      systems for effective and safe gene therapy.

PMID- 21092709
TI  - Spectroscopic studies and molecular modeling for understanding the interactions
      between cholesterol and cyclodextrins.
AB  - PURPOSE: Cholesterol is a major lipid constituent of biological membranes which
      could be included in cyclodextrin (CD) cavities. Solubilization and cell
      extraction of cholesterol have been previously performed in order to study its
      interaction with beta-CD and methylated beta-derivatives notably. The present
      work aims at confirming the formation of inclusion complexes between these CDs
      and cholesterol in order to understand their solubilization and cell extraction
      capacities. METHODS: In this context, liquid-state NMR spectroscopy (1H NMR
      studies and ROESY experiments) as well as theoretical studies (molecular
      modeling) have been performed. RESULTS: Rather than preferential conformations,
      the spectroscopic studies showed us the possible interactions between cholesterol
      and dimethyl-beta-CD, trimethyl-beta-CD, randomly methylated beta-CD or
      Crysmeb(r). Weak interactions were detected using the latter one, confirming the
      advantage of the low substitution to decrease membrane loss of integrity and
      cytotoxicity. Molecular modeling studies should be used to determine which
      stoichiometry and conformations are energetically more favorable. The semi
      empirical AM1 level was used to investigate both 1:1 and 1:2 complexes whereas
      1:1 complexes were also studied using minimal or double zeta basis sets. Four
      conformations for each 1:2 complexes have been envisaged and studied for the
      methylated CDs. CONCLUSIONS: These studies allowed us to confirm the interactions
      between cholesterol and beta-CDs especially the methylated derivatives.

PMID- 21092710
TI  - Effects of one year treatment of sibutramine on insulin resistance parameters in
      type 2 diabetic patients.
AB  - PURPOSE: Comparison of the effects of one year treatment with sibutramine
      compared to placebo on insulin resistance parameters, body weight, glycemic
      control, and lipid profile, in type 2 diabetic patients. METHODS: Two hundred and
      forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with
      different oral hypoglycemic agents or insulin were enrolled in this study and
      randomised to take sibutramine 10 mg or placebo for one year. We evaluated at
      baseline, and after 3, 6, 9, and 12 months these parameters: homeostasis model
      assessment insulin resistance index (HOMA-IR), retinol binding protein-4 (RBP-4),
      resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP), body
      weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma
      glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI),
      total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density
      lipoprotein-cholesterol (HDL-C), and triglycerides (T(g)). RESULTS: A faster
      decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared
      to the control group. We observed a significant decrease of Hs-CRP in both
      groups, and a faster improvement of HbA(1c), FPG and PPG with sibutramine
      compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL
      C, body weight, and BMI in the sibutramine group, but not in the control group.
      CONCLUSIONS: Sibutramine gave a faster improvement of insulin resistance
      parameters and glycemic control compared to placebo; furthermore sibutramine gave
      also an improvement of lipid profile, and body weight.

PMID- 21092711
TI  - Galvanostatic stripping chronopotentiometric study for determination of selenium:
      pharmacokinetic application in experimental mice.
AB  - PURPOSE: The aim of this study was to determine the selenium content in various
      tissues of the mouse employing the galvanostatic stripping chronopotentiometry
      (SCP) technique and to investigate the distribution profile of selenium as well
      as its pharmacokinetics in a mouse model. METHODS: The animals received 0.25
      MUg/g Se orally for 5 days. Samples of whole blood and various tissues comprising
      kidney, liver and brain were harvested from mice and then analysed for Se content
      employing the SCP technique. RESULTS: The SCP method was validated over Se
      concentration range of 10 - 100 ng/mL and showed good linearity (r2 > 0.999). The
      precision (over 5 days) of the assay in various mouse tissues (liver, kidney, and
      brain) ranged from 0.03 to 2.9% with accuracy results that varied from -6.69 to
      0.28%. The mean (n = 5) recoveries of Se from the mouse tissues ranged from 93.31
      to 100.28%. The lower limit of Se detection in the mouse tissues was 0.2 ng/mL.
      The present method was successfully applied in evaluating the distribution of Se
      in various tissues as well as its pharmacokinetics in the mouse model. The Se
      tissue concentrations in the mouse model showed that the maximum Se levels in
      most tissues were attained within 3-4 days following its administration.
      Furthermore, the pharmacokinetic profile of Se in the mouse model indicates that
      the element is slowly absorbed from the gastrointestinal tract (GIT) reaching a
      plateau in 4 days and then it is slowly eliminated from the body with a half-life
      of about 4.5 days. CONCLUSIONS: The present SCP method was employed to analyse Se
      in various mouse tissues. The method was characterized by excellent performance
      parameters necessary for the determination of Se in biological matrices. Se
      distributes in whole blood as well as into various tissues of the mouse with high
      concentrations in the kidney and liver and low levels in the blood and brain
      tissues. The absorption of Se from the GIT was very slow and the data suggest
      that the elimination of Se seems to be through the kidney at a very slow rate as
      well. The data of the present study thus suggest that Se remains in the mouse
      body for a long period of time.

PMID- 21092712
TI  - Smart polymeric nanofibers for topical delivery of levothyroxine.
AB  - Topical administration of levothyroxine (T4) helps to reduces deposits of adipose
      tissue on skin. The question is whether topical application of T4 could lead to
      systemic effects. In the present study a series of nanofibrous membranes were
      electrospun into blends of poly vinyl alcohol (PVA) and poly-N
      isopropylacrylamide (PNIPAM) to develop a sustained topical delivery of T4. The
      polymeric nanofiber mats were characterized by field emission scanning electron
      microscopy (FESEM) and fourier transform infrared (FTIR) spectroscopy. In vitro
      permeation of the drug from the polymeric nanofibers was studied using excised
      human skin and the permeation mechanism investigated using confocal microscopy.
      It was observed that polymeric nanofibers were able to sustain the penetration of
      T4 to the skin and help maintain the effective drug concentration in the skin
      layers for longer period of time. These formulations may have potential uses in
      topical skin products and can help to increase the accumulation of the active
      compound on the skin surface thus minimize the adverse side effects which may be
      caused by systemic absorption. This may result in great improvement in consumer
      compliance, avoid frequent dosing and enhance the therapeutic effectiveness.

PMID- 21092713
TI  - Morin improves urate excretion and kidney function through regulation of renal
      organic ion transporters in hyperuricemic mice.
AB  - PURPOSE: Morin (2',3,4',5,7-pentahydroxyflavone), a plant-derived flavonoid, has
      beneficial effects on hyperuricemia and renal dysfunction in animals. Since the
      decreased renal excretion of uric acid is the hallmark of hyperuricemia, here we
      studied the effects of oral morin administration on renal organic ion
      transporters in potassium oxonate-induced hyperuricemic mice. METHODS:
      Hyperuricemia in mice was induced by potassium oxonate. Uric acid and creatinine
      concentrations in urine and serum, and fractional excretion of uric acid (FEUA)
      were performed to evaluate renal urate handling. Changes in expression levels of
      renal organic ion transporters were detected by Western blotting and semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR) methods.
      RESULTS: Morin treatment significantly increased urinary uric acid/creatinine
      ratio and FEUA, resulting in reduction of serum uric acid levels in hyperuricemic
      mice. And kidney conditions were also improved after morin treatment in this
      model. Protein and mRNA levels of glucose transporter 9 (mGLUT9) and urate
      transporter 1 (mURAT1) were significantly decreased, and of organic anion
      transporter 1 (mOAT1) were remarkably increased in the kidney of morin-treated
      hyperuricemic mice. Morin treatment also blocked down-regulations of renal
      organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in
      hyperuricemic mice. CONCLUSION: These results suggest that morin exhibits the
      uricosuric effects via suppressing urate reabsorption and promoting urate
      secretion in the kidney of hyperuricemic mice and may help to attenuate
      deleterious effects of hyperuricemia with renal dysfunction.

PMID- 21092714
TI  - HPMC capsules: current status and future prospects.
AB  - Hydroxypropyl methylcellulose (HPMC) is employed for a wide variety of
      pharmaceutical and food preparations. Its applications as viscolizing agent
      (thickening agent), coating polymer, bioadhesive, in solid dispersion to enhance
      solubility, binder in the process of granulation and in modified release
      formulations have been well documented. One other notable use is in the
      production of capsule shells, replacing the animal derived gelatin in
      conventional two-piece capsules. The aim of this review is to systemically survey
      published literature on the HPMC use in capsule shells and resolve questions
      regarding their suitability as a replacement for hard gelatin capsules. Future
      refinements in the production and filling of HPMC capsule shells and improvement
      in their in vivo/in vitro dissolution would ensure their superiority over hard
      gelatin capsules.

PMID- 21092715
TI  - Pharmacokinetic study of modafinil in relation to gender and ethnicity in healthy
      young Chinese volunteers.
AB  - PURPOSE: Pharmacokinetics of modafinil were investigated in relation to sex and
      ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui
      (n = 10/group) following administration of a single 200 mg oral dose. METHODS:
      Blood samples were collected over 48 h for the determination of plasma levels of
      modafinil and its acid metabolite by HPLC. Pharmacokinetic parameters were
      evaluated using noncompartmental methods. RESULTS: Modafinil was well tolerated
      and safe at a single oral dose of 200 mg. All participants reported adverse
      events, none of which was serious or unexpected. The maximum plasma concentration
      (C(max)) and area under the curve for modafinil concentration versus time, which
      was extrapolated to infinity (AUC(0-infinity)), were higher in women compared to
      men (p < 0.01). No sex-based difference was noted in the total body weight
      normalized modafinil oral clearance. The total body weight-normalized modafinil
      apparent volume of distribution and t1/2 were found to exhibit ethnicity-based
      significant differences. CONCLUSION: There are pharmacokinetic differences based
      on sex and ethnicity for modafinil.

PMID- 21092716
TI  - New perspectives on innovative drug discovery: an overview.
AB  - Despite advances in technology, drug discovery is still a lengthy, expensive,
      difficult, and inefficient process, with a low rate of success. Today, advances
      in biomedical science have brought about great strides in therapeutic
      interventions for a wide spectrum of diseases. The advent of biochemical
      techniques and cutting-edge bio/chemical technologies has made available a
      plethora of practical approaches to drug screening and design. In 2010, the total
      sales of the global pharmaceutical market will reach 600 billion US dollars and
      expand to over 975 billion dollars by 2013. The aim of this review is to
      summarize available information on contemporary approaches and strategies in the
      discovery of novel therapeutic agents, especially from the complementary and
      alternative medicines, including natural products and traditional remedies such
      as Chinese herbal medicine.

PMID- 21092717
TI  - Nanoparticle-mediated interleukin-12 cancer gene therapy.
AB  - Interleukin-12 (Il-12) is a heterodimeric cytokine which has been proven to
      possess antitumor effects in various animal models via stimulating the immune
      system. However, the main problem associated with Il-12 protein delivery is its
      instability as well as cytotoxicity subsequent to systemic administration in
      rodents and in clinical trials. However, gene delivery can be used to deliver
      genes of interest to the tumor site. Hence, a large number of studies have been
      undertaken to deliver genes of interest to the tumor site through viral or non
      viral vectors. Viral DNA delivery systems suffer from safety concern due to the
      toxicity of the viruses and strong immune response, while non-viral gene delivery
      systems proffer lower transfection efficiency. In contrast, nanometer-sized
      complexes of therapeutic DNA may prove to be more efficient for administration of
      therapeutic genes to solid tumors compared to administration of naked plasmid
      DNA. Nanoparticle-based gene delivery systems might be more pertinent, due to
      enhanced tissue penetrability, and improved cellular uptake. Il-12 gene delivery
      has already been reported with different nanoparticles containing DNA. This
      article provides a review on the in vivo and in vitro studies using various
      nanoparticles, for delivery of the Il-12 gene to neoplastic cells. The future of
      these promising approaches lies in the development of better techniques for
      preparing Il-12 gene delivery systems with complete efficiency of viral vectors
      in addition to the highest safety for cancer patients.

PMID- 21092718
TI  - [Gallstones in children].

PMID- 21092719
TI  - [Need for a national database on lumbar fusion surgery].
AB  - INTRODUCTION: The indication for surgical technique in lumbar fusion is debated.
      The objective of this study was to analyse the indication and operative technique
      in lumbar surgery clinics in Denmark. MATERIAL AND METHODS: A cohort study based
      on a sample from four public and four private clinics in 2006 was used. RESULTS:
      There was no difference in patient demographics and diagnosis between public and
      private clinics. In 62% of the patient files, information was lacking.
      Considerations on indication and surgery did not differ from public to private
      clinics. A standard preoperative rehabilitation program was performed in 59% of
      the cases. Combined anterior and posterior fusion was performed in 37 cases,
      posterior instrumented fusion in 77 cases and posterior uninstrumented fusion in
      105 cases, interspinous spacer was used in six cases and disc arthroplasty in 13
      cases. CONCLUSION: Adequate evaluation of indication and choice of surgical
      technique in lumbar fusion based on patient files was not possible. We found no
      qualitative differences between public and private clinics. A national database
      is needed to monitor indication and choice of operative procedure.

PMID- 21092720
TI  - [Differences in the treatment of idiopathic thrombocytopenic purpura in
      children].
AB  - INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is a rare immune-mediated
      bleeding disorder that usually takes a self-limiting and benign course. Due to
      the risk of intracranial haemorrhage, treatment regimens tend to be active. We
      present treatment data from 17 paediatric departments in Denmark (1998-2000),
      focusing on regional differences in treatment strategy. MATERIAL AND METHODS: As
      part of a prospective Nordic study, clinical findings and treatment were recorded
      for 109 children with newly diagnosed ITP. The course in the following six months
      was reported for 91 children. Results are compared for three geographical
      regions: East, North and South. RESULTS: Pharmacotherapy, almost exclusively
      intravenous immunoglobulin, was given within 14 days of diagnosis to 89%, 70%,
      and 48% in regions East, North, and South, respectively. A very low platelet
      count was the main indication. Platelet transfusion was given to 24%, 0% and 4%,
      respectively. There were no differences in remission rates or frequency of
      mucosal bleeding during follow-up, but treatment rates were 6.3, 4.7, and 3.0 per
      patient-year with severe thrombocytopenia. Chronic ITP lasting more than six
      months developed in 26%, 33%, and 18%, respectively. CONCLUSION: We found obvious
      regional differences in treatment strategy which reflect differences in
      international clinical guidelines. The initial treatment approach had no
      influence on morbidity, time of remission or risk of chronic course.

PMID- 21092721
TI  - [''Liva"--population survey of female sexual habits].
AB  - INTRODUCTION: Sexual and contraceptive habits, e.g. early age at first
      intercourse, multiple sexual partners and non-use of condoms, are well
      established risk factors for sexually transmitted infections and unwanted
      pregnancy. The aim was to examine if and how educational level and degree of
      urbanization are related to age at first intercourse, lifetime number of sexual
      partners and condom use. MATERIAL AND METHODS: We used data from a large
      population-based questionnaire survey conducted during 2004-2005, including a
      random sample of 20,478 women (18-45 years) (participation rate: 81.4%). We used
      multiple logistic regression analysis to estimate odds ratios (OR) of early
      sexual debut (<= 15 years old), having had > 5 lifetime sexual partners and never
      use of condoms associated with educational level and degree of urbanization. The
      OR of having had an early sexual debut was almost twofold higher among women with
      a lower educational level (OR = 1.93; 95% CI: 1.73-2.15) than among women with
      higher educational level, and the OR of having had > 5 lifetime sexual partners
      was highest among women in the capital centre (OR = 2.36; 95% CI: 2.16-2.57)
      compared with women in the small provincial town areas. Furthermore, the OR of
      never-use of condoms was 2.53 (95% CI: 2.15-2.97) for women with a lower
      educational level compared with those with a higher educational level (mutually
      adjusted for age, degree of urbanization and educational level). CONCLUSION: Low
      educational level is associated with young age at first sexual intercourse and
      never-use of condoms, and living in an area of high urbanization is associated
      with a higher lifetime number of sexual partners. This information may be of
      importance for prevention in relation to women's reproductive health.

PMID- 21092722
TI  - [Indacaterol is a new once-daily beta2-agonist for treatment of COPD].
AB  - The aim of pharmacological treatment of COPD is best possible disease control.
      Bronchodilators are accepted as the mainstay of COPD therapy. This short review
      focuses on the available data on indacaterol - a new once-daily beta2-agonist.
      The analysed studies show that indacaterol has clinically important effects on
      quality of life, dyspnoea, level of FEV1, hyperinflation, and exacerbation rate
      in patients with COPD. Indacaterol is therefore in the near future expected to be
      an important part of maintenance therapy for patients with COPD.

PMID- 21092723
TI  - [ABCDE--a systematic approach to critically ill patients].
AB  - This systematic approach to the immediate assessment and treatment of the
      critically ill or injured patient is applicable in all clinical emergencies. The
      aim of the ABCDE approach is to facilitate immediate life-saving treatment and
      thus buy time for definite diagnosis and treatment by breaking down complex
      clinical situations into manageable parts. Application of the ABCDE approach may
      improve treatment quality.

PMID- 21092724
TI  - [Generalized dystrophic epidermolysis bullosa and development of squamous cell
      carcinoma].
AB  - Severe generalized dystrophic epidermolysis bullosa is described via a clinical
      case in an adult male. From the time of birth his skin was characterized by
      extensive blistering, slowly developing into chronic wounds with the formation of
      pseudosyndactyly. As he grew older extracutaneous involvement from other organ
      systems was seen. Specifically, the patient presented with chronic anaemia,
      growth retardation and ocular findings. At the age of 45, squamous cell
      carcinomas to the extremities indicate imminent amputation in an attempt to
      improve survival probability.

PMID- 21092725
TI  - [Fish odour--could be a sign of trimethylaminuria].
AB  - We present a case with a ten-year-old girl with trimethylaminuria (TMAU). Primary
      TMAU is caused by a deficiency of flavin monooxygenase 3 (FMO3) due to mutations
      in the FMO3-gene. Patients suffering from TMAU show an impaired enzymatic
      oxidation of fish-smelling trimethylamine, and their excretion of this amine in
      body fluids produces an unpleasant body odour. TMAU is also seen secondary to
      e.g. liver diseases. It remains unknown if TMAU causes other problems than
      malodour, and today social and psychological problems are considered the most
      important consequence. Treatment includes a low-choline diet and antibiotics.

PMID- 21092733
TI  - Hetero-oligomeric cell wall channels (porins) of Nocardia farcinica.
AB  - The cell wall of Nocardia farcinica contains a cation-selective cell wall
      channel, which may be responsible for the limited permeability of the cell wall
      of N. farcinica for negatively charged antibiotics. Based on partial sequencing
      of the protein responsible for channel formation derived from N. farcinica ATTC
      3318 we were able to identify the corresponding genes (nfa15890 and nfa15900)
      within the known genome of N. farcinica IFM 10152. The corresponding genes of N.
      farcinica ATTC 3318 were separately expressed in the Escherichia coli BL21DE3Omp8
      strain and the N-terminal His10-tagged proteins were purified to homogeneity
      using immobilized metal affinity chromatography. The pure proteins were
      designated NfpANHis and NfpBNHis, for N. farcinica porin A and N. farcinica porin
      B. The two proteins were checked separately for channel formation in lipid
      bilayers. Our results clearly indicate that the proteins NfpANHis and NfpBNHis
      expressed in E. coli could only together form a channel in lipid bilayer
      membranes. This means that the cell wall channel of N. farcinica is formed by a
      heterooligomer. NfpA and NfpB form together a channel that may structurally be
      related to MspA of Mycobacterium smegmatis based on amino acid comparison and
      renaturation procedure.

PMID- 21092734
TI  - Vitamin A supplementation in rats under pregnancy and nursing induces behavioral
      changes and oxidative stress upon striatum and hippocampus of dams and their
      offspring.
AB  - Vitamin A is important for both development and maintenance of adult brain
      homeostasis. However, excessive vitamin A exposure has been linked to cognitive
      impairments and may induce congenital defects, including neuronal malformations.
      Recently, we demonstrated that vitamin A supplementation is able to alter
      behavioral parameters and induce a pro-oxidant state in hippocampus and striatum
      of adult male rat. Thus, the aim of the present work was to investigate the
      effects of vitamin A supplementation in pregnant and nursing rats on maternal and
      offspring striatum and hippocampus. Wistar female rats (7 per group) were orally
      supplemented with retinyl palmitate (2500, 12,500 and 25,000 IU/kg/day) or saline
      (control) throughout pregnancy and nursing. Homing test was performed at
      postnatal days (PND) 5 and 10 for offspring, while open field test (OFT) was
      carried out at PND19 and 20 for dams and offspring, respectively. Redox
      parameters were evaluated at PND21 for both. Vitamin A supplementation during
      pregnancy and nursing increased superoxide dismutase/catalase (SOD/CAT) ratio and
      oxidative damage in maternal and offspring striatum and hippocampus.
      Additionally, supplementation induced behavioral alterations. In conclusion, we
      suggest some caution regarding vitamin A intake during pregnancy and
      breastfeeding, since oxidative stress can disturb several biological phenomena,
      including neuronal signaling and neurotransmission, which may induce several
      behavioral deficits.

PMID- 21092735
TI  - 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after
      spinal cord injury.
AB  - The study investigated the mechanism of the up-regulation of aquaporin-4 (AQP4)
      and aquaporin-1 (AQP1) expression induced by spinal cord injury (SCI). Using
      adult rat spinal cord injury model, it was found that up-regulation of hypoxia
      inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF),
      AQP4, and AQP1 in response to spinal cord injury was greatly antagonized by 2
      methoxyestradiol (2ME2), which can post-transcriptionally inhibit the expression
      of HIF-1alpha. VEGF alone significantly increased the extravasation of Evans blue
      and up-regulated the levels of AQP4 protein expression in the injured spinal cord
      issue, but the levels of AQP1 expression were not significantly changed. Taken
      together, our results suggest that expression of AQP4 and AQP1 is correlated with
      up-regulation of HIF-1alpha after SCI through the mechanisms that were dependent
      and independent of the VEGF signaling pathway, respectively. And the inhibitor of
      HIF-1alpha is a novel promising therapeutic agent for human SCI-induced edema in
      the future.

PMID- 21092736
TI  - Simultaneous determination of tryptophan, kynurenine and 5-hydroxytryptamine by
      HPLC: Application in uremic patients undergoing hemodialysis.
AB  - OBJECTIVES: To develop a reliable HPLC method for the simultaneous determination
      of plasma tryptophan, kynurenine and 5-hydroxytryptamine to analyze tryptophan
      metabolism. DESIGN AND METHODS: Separation was carried out on a C8 column with
      the mobile phase composed of acetate buffer (pH 4.5) and acetonitrile using
      theophylline as internal standard. The eluates were monitored by ultraviolet
      detection with programmed wavelength. RESULTS: Analysis was achieved in less than
      8.0min. The limits of quantification were 3.97MUmol/L, 4.36nmol/L and
      0.421MUmol/L for tryptophan, 5-hydroxytryptamine and kynurenine, respectively.
      Reproducibility and recovery were satisfactory. Twenty healthy adults and 20
      uremic patients undergoing hemodialysis were analyzed using the present method.
      Tryptophan metabolism was found to be disturbed in uremic patients and was
      improved obviously after hemodialysis. CONCLUSIONS: The developed HPLC method is
      simple, reliable and suitable for monitoring tryptophan metabolism in uremic
      patients undergoing hemodialysis.

PMID- 21092737
TI  - Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle
      function in Caenorhabditis elegans.
AB  - Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) from
      nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD(+)
      after it is hydrolyzed. This pathway is emerging as a regulator of multiple
      biological processes. Here we probe the contribution of the NAM-NAD(+) salvage
      pathway to muscle development and function using Caenorhabditis elegans. C.
      elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the
      first step of this NAD(+) salvage pathway, cannot mate due to a spicule muscle
      defect. Multiple muscle types are impaired in the hermaphrodites, including body
      wall muscles, pharyngeal muscles and vulval muscles. An active NAD(+) salvage
      pathway is required for optimal function of each muscle cell type. However, we
      found surprising muscle-cell-type specificity in terms of both the timing and
      relative sensitivity to perturbation of NAD(+) production or NAM levels. Active
      NAD(+) biosynthesis during development is critical for function of the male
      spicule protractor muscles during adulthood, but these muscles can surprisingly
      do without salvage biosynthesis in adulthood under the conditions examined. The
      body wall muscles require ongoing NAD(+) salvage biosynthesis both during
      development and adulthood for maximum function. The vulval muscles do not
      function in the presence of elevated NAM concentrations, but NAM supplementation
      is only slightly deleterious to body wall muscles during development or upon
      acute application in adults. Thus, the pathway plays distinct roles in different
      tissues. As NAM-NAD(+) biosynthesis also impacts muscle differentiation in
      vertebrates, we propose that similar complexities may be found among vertebrate
      muscle cell types.

PMID- 21092738
TI  - PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the
      presence of growth factors.
AB  - Correct guidance of the migration of neural progenitor cells (NPCs) is essential
      for the development and repair of the central nervous system (CNS). Electric
      field (EF)-guided migration, electrotaxis, has been observed in many cell types.
      We report here that, in applied EFs of physiological magnitude, embryonic and
      adult NPCs show marked electrotaxis, which is dependent on the PI3K/Akt pathway.
      The electrotaxis was also evidenced by ex vivo investigation that transplanted
      NPCs migrated directionally towards cathode in organotypic spinal cord slice
      model when treated with EFs. Genetic disruption or pharmacological inhibition of
      phosphoinositide 3-kinase (PI3K) impaired electrotaxis, whereas EF exposure
      increased Akt phosphorylation in a growth factor-dependent manner and increased
      phosphatidylinositol-3,4,5-trisphosphate (PIP3) levels. EF treatments also
      induced asymmetric redistribution of PIP3, growth factor receptors, and actin
      cytoskeleton. Electrotaxis in both embryonic and adult NPCs requires epidermal
      growth factor (EGF) and fibroblast growth factor (FGF). Our results demonstrate
      the importance of the PI3K/Akt pathway in directed migration of NPCs driven by
      EFs and growth factors and highlight the potential of EFs to enhance the guidance
      of various NPC populations in CNS repair therapies.

PMID- 21092739
TI  - PCSK2-null mice exhibit delayed intestinal motility, reduced refeeding response
      and altered plasma levels of several regulatory peptides.
AB  - AIMS: To examine the effects of global lack of proprotein convertase
      subtilisin/kexin 2 (PCSK2) in mouse on intestinal motility, post-fast refeeding
      response and levels of several PCSK-generated peptides known to regulate food
      intake and processing. MAIN METHODS: Using male and female PCSK2 knockout (KO)
      and wild-type (WT) mice, intestinal motility was assessed by determining the
      percent of intestinal length travelled by a charcoal-dyed meal following an oral
      gavage; the refeeding response by measuring the amount of meal consumed following
      an overnight fast; the levels of the regulatory peptides by enzyme immunoassays
      or immunoblotting. KEY FINDINGS: Relative to same-gender WT mice, KO mice
      exhibited delayed intestinal transit (P<0.001 in females; P<0.05 in males). Their
      post-fast feeding response was reduced in females during the first hour of
      refeeding (P<0.05). The circulating level of substance P (SP) was lower (P<0.001
      in females; P<0.05 in males); it was higher for somatostatin (SS) (P<0.001 in
      females; P<0.05 in males) and GLP-1 (P<0.001 in females; P<0.01 in males) and GLP
      2 (P<0.001 in both genders); it was higher for peptide YY (PYY) in female mice
      only (P<0.01). Processing of brain proneuropeptide Y was impaired in both
      genders. SIGNIFICANCE: The alterations in intestinal motility and post-fast
      refeeding response observed in PCSK2-KO mice correlate with changes in the
      circulating and tissue levels of the regulatory peptides tested, suggesting that
      PCSK2 is needed for normal food intake and processing.

PMID- 21092740
TI  - Estrogen dependence of the renal vasodilatory effect of nicotine in rats: role of
      alpha7 nicotinic cholinergic receptor/eNOS signaling.
AB  - AIMS: We recently reported that acute exposure to nicotine vasodilates the renal
      vasculature of male rats via facilitation of endothelial nitric oxide synthase
      (eNOS). In this study, we investigated whether this effect of nicotine is
      sexually dimorphic and the role of estrogen in modulating the nicotine effect.
      MAIN METHODS: Nicotine-evoked vasodilation was evaluated in phenylephrine
      preconstricted perfused kidneys obtained from male, proestrus female,
      ovariectomized (OVX) and estrogen-replaced OVX (OVXE(2)) rats. KEY FINDINGS:
      Nicotine infusion (5*10(-5), 1*10(-4), and 5*10(-4) M) produced greater
      concentration-dependent reductions in the renal perfusion pressure (RPP) in an
      isolated kidney from proestrus females than from males. Inhibition of NOS by N(G)
      nitro-L-arginine abolished the nicotine-evoked reduction in RPP and abolished the
      gender difference in the nicotine effect. Nicotine vasodilation was also
      attenuated in kidneys isolated from OVX and diestrus rats, models characterized
      by reduced estrogen levels. Further, estrogen or L-arginine supplementation in
      OVX rats largely restored the renal vasodilatory response to nicotine. Estrogen
      receptor blockade by tamoxifen abrogated the enhanced nicotine-evoked
      vasodilation elicited by E(2) in OVX rats. The nitrite/nitrate levels and protein
      expressions of eNOS and alpha(7) nicotinic cholinergic receptor (alpha(7) nAChRs)
      were significantly higher in renal tissues of OVXE(2) compared with OVX rats,
      suggesting a facilitatory effect for E(2) on alpha(7) nAChRs/eNOS signaling.
      SIGNIFICANCE: Estrogen-dependent facilitation of NOS signaling mediates the
      enhanced vasodilator capacity of nicotine in the renal vasculature of female
      rats. Preliminary evidence also suggests a potential role for alpha(7) nAChRs in
      this estrogen-dependent phenomenon.

PMID- 21092741
TI  - Breed differences in behavioural response to challenging situations in kittens.
AB  - In a previous experiment, the behaviour of Oriental/Siamese/Abyssinian (OSA)
      kittens was compared with that of Norwegian Forest kittens (NFO) in a repeated
      Open Field Test (OFT), and significant differences emerged. To further
      investigate such variations, we analyzed kittens' responses to a potentially
      threatening object (TO) during the OFT. It was a metal spring enveloped in a
      cotton case suddenly bouncing out of the cylinder after the first 6 min of OFT
      exposure, and the test lasted 6 more minutes. From the 4th to the 10th week of
      age, during each test, the response of 43 OSA kittens and 39 NFO kittens to the
      TO was analyzed. Heart rate (HR) before and after the test was recorded.
      Behaviours were recorded and analyzed by focal animal sampling. Behavioural
      modifications recorded after TO exposure confirmed our suggestions on slow limbic
      system development in NFO kittens, as previously suggested by poor habituation
      and poor memory retention of repeated OFT exposure. The evident avoiding response
      to the TO confirmed the adoption in NFO kittens of an active-coping strategy
      towards challenge, as indicated also by their high scores for exploration and
      escape attempts. Otherwise, poor TO influence on exploration observed in OSA
      kittens suggested the adoption of a passive coping strategy, as previously shown
      by low levels of exploration and intra-session reduction in the number of
      vocalizations. Nevertheless, some of the behaviours observed, and the evidence of
      emotional tachycardia in OSA kittens, suggested also that the low level of
      activity recorded could have been due to a low arousability predisposition in
      this breed. The perception of a poorly arousing potential in the experimental
      setting might have influenced the perception of danger and the behaviour adopted
      in OSA kittens.

PMID- 21092743
TI  - The importance of corticosterone in mediating restraint-induced weight loss in
      rats.
AB  - I. J. Scherer, P. V. Holmes, R. B.S. Harris. The importance of corticosterone in
      mediating restraint-induced weight loss in rats. PHYSIOL BEHAV 00 (0) 000-000,
      2010. Rats restrained for 3 h/day for 3d ays (RR) lose weight and do not return
      to the weight of non-restrained controls once restraint has ended. This study
      tested the importance of restraint-induced corticosterone release in mediating
      the change in body weight by injecting ADX rats with 2.0mg corticosterone/kg
      before each restraint to replicate the restraint-induced surge in circulating
      corticosterone. Restrained adrenalectomized (ADX) rats injected with
      corticosterone had the same initial weight loss as intact restrained rats,
      whereas corticosterone injection in non-restrained ADX rats and restraint of ADX
      rats injected with saline each produced only half as much initial weight loss.
      Sustained weight loss, measured for 14 days after the end of RR, was the same for
      restrained intact rats and restrained ADX rats injected with corticosterone
      whereas restrained ADX rats injected with saline achieved the same weight gain as
      their controls. Corticosterone injections had no effect on weight gain of non
      restrained intact rats. In situ hybridization showed that corticotropin releasing
      factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus
      (PVN) was increased by the same degree in ADX rats and restrained intact rats and
      was not modified by corticosterone injections. There was no significant effect of
      restraint, ADX or corticosterone injection on PVN arginine vasopressin (AVP) mRNA
      expression. These data indicate that a surge in corticosterone causes sustained
      weight loss in ADX rats through a mechanism that can be compensated for in intact
      rats and is independent of changes in PVN CRF or AVP mRNA expression.

PMID- 21092742
TI  - Disruption of the neuregulin 1 gene in the rat alters HPA axis activity and
      behavioral responses to environmental stimuli.
AB  - Exposure to stress can result in an increased risk for psychiatric disorders,
      especially among genetically predisposed individuals. Neuregulin 1 (NRG1) is a
      susceptibility gene for schizophrenia and is also associated with psychotic
      bipolar disorder. In the rat, the neurons of the hypothalamic paraventricular
      nucleus show strong expression of Nrg1 mRNA. In patients with schizophrenia, a
      single nucleotide polymorphism in the 5' region of NRG1 interacts with
      psychosocial stress to affect reactivity to expressed emotion. However, there is
      virtually no information on the role of NRG1 in hypothalamic-pituitary-adrenal
      axis function, and whether the protein is expressed in the paraventricular
      nucleus is unknown. The present studies utilize a unique line of Nrg1 hypomorphic
      rats (Nrg1(Tn)) generated by gene trapping with the Sleeping Beauty transposon.
      We first established that the Nrg1(Tn) rats displayed reduced expression of both
      the mRNA and protein corresponding to the Type II NRG1 isoform. After confirming,
      using wild type animals, that Type II NRG1 is expressed in the neurocircuitry
      involved in regulating hypothalamic-pituitary-adrenal axis responses to
      environmental stimuli, the Nrg1(Tn) rats were then used to test the hypothesis
      that altered expression of Type II NRG1 disrupts stress regulation and
      reactivity. In support of this hypothesis, Nrg1(Tn) rats have disrupted basal and
      acute stress recovery corticosterone secretion, differential changes in
      expression of glucocorticoid receptors in the pituitary, paraventricular nucleus
      and hippocampus, and a failure to habituate to an open field. Together, these
      findings point to NRG1 as a potential novel regulator of neuroendocrine responses
      to stress as well as behavioral reactivity.

PMID- 21092744
TI  - FOXO3a reactivation mediates the synergistic cytotoxic effects of rapamycin and
      cisplatin in oral squamous cell carcinoma cells.
AB  - FOXO3a, a well-known transcriptional regulator, controls a wide spectrum of
      biological processes. The phosphoinositide-3-kinase (PI3K)/Akt signaling pathway
      inactivates FOXO3a via phosphorylation-induced nuclear exclusion and degradation.
      A loss or gain of FOXO3a activity has been correlated with efficiency of
      chemotherapies in various cancers including oral squamous cell carcinoma (OSCC).
      Therefore, in the current study, we have investigated the FOXO3a activity
      modulating and antitumor effects of rapamycin and cisplatin in OSCC cells.
      Cisplatin inhibited proliferation and induced apoptosis in a dose-dependent way
      in OSCC Tca8113 cells. Rapamycin alone had no effect on cell proliferation and
      apoptosis. Rapamycin downregulated the expression of S-phase kinase associated
      protein-2 (Skp2) and increased the FOXO3a protein stability but induced the
      upregulation of feedback Akt activation-mediated FOXO3a phosphorylation.
      Cisplatin decreased the phosphorylation of FOXO3a via Akt inhibition. Rapamycin
      combined with cisplatin as its feedback Akt activation inhibitor revealed the
      most dramatic FOXO3a nuclear localization and reactivation with the prevention of
      its feedback loop and exposed significant synergistic effects of decreased cell
      proliferation and increased apoptosis in vitro and decreased tumor size in vivo.
      Furthermore, the downstream effects of FOXO3a reactivation were found to be
      accumulation of p27 and Bim. In conclusion, rapamycin/cisplatin combination
      therapy boosts synergistic antitumor effects through the significant FOXO3a
      reactivation in OSCC cells. These results may represent a novel mechanism by
      which rapamycin/cisplatin combination therapy proves to be a potent molecular
      targeted strategy for OSCC.

PMID- 21092745
TI  - Implied motion from static photographs influences the perceived position of
      stationary objects.
AB  - A growing amount of evidence suggests that viewing a photograph depicting motion
      activates the same direction-selective neurons involved in the perception of real
      motion. It has been shown that prolonged exposure (adaptation) to photographs
      depicting directional motion can induce motion adaptation and consequently motion
      aftereffect. The present study investigated whether adapting to photographs
      depicting humans, animals, and vehicles that move leftward or rightward also
      generates a positional aftereffect (the motion-induced position shift--MIPS), in
      which the perceived spatial position of a target pattern is shifted in the
      opposite direction to that of adaptation. Results showed that adapting to still
      photographs depicting objects that move in a particular direction shifts the
      perceived position of subsequently presented stationary objects opposite to the
      depicted adaptation direction and that this effect depends on the retinotopic
      location of the adapting stimulus. These results suggest that the implied motion
      could activate the same direction-selective and speed-tuned mechanisms that
      produce positional aftereffect when viewing real motion.

PMID- 21092746
TI  - Alterations in visual and auditory processing in hemispatial neglect: an evoked
      potential follow-up study.
AB  - Hemispatial neglect is common after cerebrovascular stroke in the right
      hemisphere. Cortical electrophysiological studies, especially investigations of
      both visual and auditory processing in subjects with neglect are sparse. Our
      purpose was to assess whether and to which extent subjects with neglect may show
      impairments in both visual and auditory processing. Thereby, we assessed the
      evolution of changes in sensory processing and neglect symptoms over a 6 month
      follow-up period. Twenty-one stroke subjects with hemispatial neglect were
      studied at baseline, 3 weeks later and at 6 months follow-up. At enrollment, 12
      patients were in Acute/subacute and 9 were in the chronic stage of stroke. Visual
      and auditory evoked potentials (EP) were elicited with unilateral stimulations
      and electrophysiologic data were registered with high-density EEG. Primary visual
      and auditory cortex activations seen in EP components were analyzed at three time
      points in order to detect alterations. Both sensory modalities revealed
      differences between hemispheres in processing stimuli coming from a unilateral
      source. Amplitudes of visual and auditory EP components elicited by left-sided
      stimuli were smaller compared to those elicited by right-sided stimuli in the
      Acute/subacute group. The behavioral neglect was more severe in those who had
      smaller EP amplitudes (e.g. EP amplitude after the right auditory stimulus was
      significantly associated with total behavioral neglect score, r=0.57). The main
      hemispheric differences diminished by the follow-up 6 months later along with the
      decreasing severity of neglect in the Acute/subacute group.

PMID- 21092747
TI  - p53 activation mediates polyglutamine-expanded ataxin-3 upregulation of Bax
      expression in cerebellar and pontine nuclei neurons.
AB  - Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative
      disorder caused by polyglutamine-expanded ataxin-3. SCA3 neurodegeneration is
      found in the pontine nuclei and cerebellum. Polyglutamine-expanded ataxin-3-Q79
      caused apoptotic death of cerebellar and pontine nuclei neurons by upregulating
      mRNA expression of pro-apoptotic Bax and activating mitochondria-mediated
      apoptotic cascade. Following various cellular stresses, transcription factor p53
      promotes apoptotic neuronal death by enhancing the transcription of pro-apoptotic
      genes including Bax and PUMA. In the present study, cellular and animal models of
      SCA3 were used to test the hypothesis that mutant polyglutamine ataxin-3
      upregulates Bax expression of cerebellar and pontine nuclei neurons by augmenting
      transcriptional activity of p53. Electrophoretic mobility shift assay (EMSA)
      indicated that p53 binding activity to Bax promoter sequence was significantly
      enhanced in cultured cerebellar neurons expressing mutant ataxin-3-Q79 and
      pontine nuclei and cerebellum of SCA3 transgenic mice expressing ataxin-3-Q79.
      The mRNA level of PUMA, a p53-inducible pro-apoptotic gene, was increased in the
      cerebellum and pontine nuclei of SCA3 transgenic mice and cultured cerebellar
      neurons expressing ataxin-3-Q79. Mutant polyglutamine ataxin-3 increased the
      protein level of active phospho-p53(Ser15) in cerebellar and pontine nuclei
      neurons without affecting mRNA or protein level of p53. Intraperitoneal
      administration of p53 inhibitor pifithrin-alpha significantly ameliorated
      neuronal death in the pontine nuclei of SCA3 transgenic mice. Our results suggest
      that polyglutamine-expanded ataxin-3 upregulates mRNA expression of Bax and PUMA
      and causes apoptotic death of affected neurons by enhancing phosphorylation and
      transcriptional activity of p53.

PMID- 21092748
TI  - A double-blind study of paliperidone palmitate and risperidone long-acting
      injectable in adults with schizophrenia.
AB  - This 13-week double-blind study was designed to assess noninferiority of the
      recently approved (in the U.S.) injectable atypical antipsychotic paliperidone
      palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult
      patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a)
      PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once
      monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or
      100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI:
      gluteal injections days 8 and 22 (25mg), days 36, 50 (25 or 37.5mg) and days 64,
      78 (25, 37.5 or 50mg). RIS-LAI-treated patients received oral supplementation
      with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral
      placebo. The safety analysis set (n=1214) included 58% men, 78% white, with mean
      (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28).
      Mean (SD) change from baseline to endpoint in PANSS total score decreased
      similarly in both groups; PP (-18.6 [15.45]) and RIS-LAI (-17.9 [14.24]). PP
      treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [-1.62;2.38],
      per-protocol analysis set [primary analysis]). The tolerability and safety of PP
      was generally similar to RIS-LAI with no new safety or tolerability findings.

PMID- 21092749
TI  - Glycine soya diet synergistically enhances the suppressive effect of tamoxifen
      and inhibits tamoxifen-promoted hepatocarcinogenesis in 7,12
      dimethylbenz[alpha]anthracene-induced rat mammary tumor model.
AB  - There is increasing interest in phytoestrogens as potential alternatives to
      synthetic selective estrogen receptor modulators (SERMs) in the prevention and
      therapy of breast cancer. The present study is aimed at determining whether
      dietary glycine soya (Glycine max seeds; GS), which is rich in phytoestrogens,
      can enhance the anti breast cancer efficacy of the SERM tamoxifen (TAM) and the
      effect of TAM and GS, either alone or in combination, on DMBA-initiated
      hepatocarcinogenesis in rat. For determination of enhancing effect, rats bearing
      palpable 7, 12-dimethylbenz[alpha] anthracene (DMBA)-induced mammary tumors were
      treated with TAM (10 mg kg(-1)/day) while being fed AIN-93G diet with or without
      added GS (3*10(4) mg kg(-1)), and the tumor growth was monitored up to 5 weeks of
      treatment. For determining the effect on hepatocarcinogenesis, DMBA-initiated
      rats were exposed to TAM and dietary GS as above for 6 weeks during promotion
      stage in a medium-term bioassay, and the development of placental form of
      glutathione-S-transferase (GST-P)-expressing preneoplastic liver lesions was
      quantified. Exposure to both TAM and dietary GS enhanced the anti tumor efficacy
      of TAM via a combination of tumor cell apoptosis (determined by TUNEL) and
      inhibition of tumor cell proliferation (determined by PCNA immunostaining) and
      suppressed the growth of GST-P-positive liver lesions. The findings show that
      dietary GS enhances the therapeutic efficacy of TAM against mammary tumors and
      minimizes TAM's hepatocarcinogenesis promotion potential.

PMID- 21092750
TI  - Ionic liquid-based dispersive liquid-liquid microextraction and enhanced
      spectrophotometric determination of molybdenum (VI) in water and plant leaves
      samples by FO-LADS.
AB  - A new simple and rapid ionic liquid-based dispersive liquid-liquid
      microextraction (IL-DLLME) has been applied to preconcentrate trace levels of
      molybdenum (VI) as a prior step to its enhanced determination by fiber optic
      linear array detection spectrophotometry (FO-LADS). In this method, a small
      amount of [Hmim][Tf(2)N] (1-hexyl-3-methylimmidazolium bis
      (trifluormethylsulfonyl) imid) as an extraction solvent was applied to extract
      molybdenum - pyrogallol red complex, which was formed in an aqueous solution in
      the presence of N-cetyl-N-N-N-trimethyl ammonium chloride as a sensitizing agent.
      Under optimum conditions, enhancement factor, detection limit and relative
      standard deviation (n=5, for 30 MUg L(-1) of molybdenum (VI)) in 10 mL water
      sample were 72.6, 1.43 MUg L(-1) and 2.8%, respectively.

PMID- 21092751
TI  - Extraction and identification of three major aldose reductase inhibitors from
      Artemisia montana.
AB  - Aldose reductase inhibitors (ARIs) provide an important therapeutic and
      preventive opportunity against hyperglycemia associated diabetic complications.
      The methanolic extracts of 12 species from the genus Artemisia exhibited
      significant in vitro rat lens AR (RLAR) inhibitory activities with IC(50) values
      ranging from 0.51 to 13.45 MUg/mL (quercetin, 0.64 MUg/mL). Since the whole plant
      of Artemisia montana showed the highest RLAR inhibitory activity, bioassay-guided
      fractionation was performed to obtain ethyl acetate and n-butanol fractions.
      Repeated column chromatography of two active fractions, yielded fifteen
      compounds, including four chlorogenic acids (3,5-di-O-caffeoylquinic acid,
      chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid), six flavonoids
      (apigenin, luteolin, quercetin, isoquercitrin, hyperoside, luteolin 7
      rutinoside), and five coumarins (umbelliferone, scoparone, scopoletin, esculetin,
      and scopolin); their structures were confirmed by spectroscopic methods. 3,5-Di-O
      caffeoylquinic acid and chlorogenic acid, as well as test flavonoids, displayed
      the most potent RLAR inhibitory activities with IC(50) values ranging from 0.19
      to 5.37 MUM. Furthermore, the HPLC profiles of the ethyl acetate and n-butanol
      fractions indicated that 3,5-di-O-caffeoylquinic acid, chlorogenic acid, and
      hyperoside, as major compounds, might play crucial roles in RLAR inhibition. The
      results suggest that A. montana and three key AR inhibitors therein would clearly
      be potential candidates as therapeutic or preventive agents for diabetic
      complications.

PMID- 21092752
TI  - Chimeric mitochondrial minichromosomes of the human body louse, Pediculus
      humanus: evidence for homologous and non-homologous recombination.
AB  - The mitochondrial (mt) genome of the human body louse, Pediculus humanus,
      consists of 18 minichromosomes. Each minichromosome is 3 to 4 kb long and has 1
      to 3 genes. There is unequivocal evidence for recombination between different mt
      minichromosomes in P. humanus. It is not known, however, how these
      minichromosomes recombine. Here, we report the discovery of eight chimeric mt
      minichromosomes in P. humanus. We classify these chimeric mt minichromosomes into
      two groups: Group I and Group II. Group I chimeric minichromosomes contain parts
      of two different protein-coding genes that are from different minichromosomes.
      The two parts of protein-coding genes in each Group I chimeric minichromosome are
      joined at a microhomologous nucleotide sequence; microhomologous nucleotide
      sequences are hallmarks of non-homologous recombination. Group II chimeric
      minichromosomes contain all of the genes and the non-coding regions of two
      different minichromosomes. The conserved sequence blocks in the non-coding
      regions of Group II chimeric minichromosomes resemble the "recombination repeats"
      in the non-coding regions of the mt genomes of higher plants. These repeats are
      essential to homologous recombination in higher plants. Our analyses of the
      nucleotide sequences of chimeric mt minichromosomes indicate both homologous and
      non-homologous recombination between minichromosomes in the mitochondria of the
      human body louse.

PMID- 21092753
TI  - Increased advanced oxidation of protein products and enhanced total antioxidant
      capacity in plasma by action of toxins of Escherichia coli STEC.
AB  - Shiga toxin (Stx) and hemolysin (Hly) of Escherichia coli O157:H7 produced an
      increase of reactive oxygen species (ROS) in normal human blood. In vitro assays
      showed that stimuli of ROS with these toxins oxidized proteins to carbonyls in
      plasma and raised the degradation of oxidized macromolecules, with the
      AOPP/carbonyl relationship also increasing. The oxidative stress generated by
      toxins during the Hemolytic Uremic Syndrome (HUS) produced oxidation of blood
      proteins with a rise in advanced oxidation protein products (AOPP) in children
      with HUS. There was a response from the antioxidant system in these patients,
      evaluated through the determination of the total antioxidant capacity of plasma
      by the Ferric Reducing Antioxidant Power (FRAP), which reduced the stimuli of ROS
      during in vitro incubation with Stx or Hly. The application of natural
      antioxidants was sufficient to reduce in vitro the oxidative stress provoked by
      both toxins in blood.

PMID- 21092754
TI  - ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human
      epidermal cells.
AB  - Titanium dioxide nanoparticles (TiO(2) NPs) are among the top five NPs used in
      consumer products, paints and pharmaceutical preparations. Since, exposure to
      such nanoparticles is mainly through the skin and inhalation, the present study
      was conducted in the human epidermal cells (A431). A mild cytotoxic response of
      TiO(2) NPs was observed as evident by the MTT and NR uptake assays after 48 h of
      exposure. However, a statistically significant (p<0.05) induction in the DNA
      damage was observed by the Fpg-modified Comet assay in cells exposed to 0.8
      MUg/ml TiO(2) NPs (2.20+/-0.26 vs. control 1.24+/-0.04) and higher concentrations
      for 6 h. A significant (p<0.05) induction in micronucleus formation was also
      observed at the above concentration (14.67+/-1.20 vs. control 9.33+/-1.00).
      TiO(2) NPs elicited a significant (p<0.05) reduction in glutathione (15.76%) with
      a concomitant increase in lipid hydroperoxide (60.51%; p<0.05) and reactive
      oxygen species (ROS) generation (49.2%; p<0.05) after 6h exposure. Our data
      demonstrate that TiO(2) NPs have a mild cytotoxic potential. However, they induce
      ROS and oxidative stress leading to oxidative DNA damage and micronucleus
      formation, a probable mechanism of genotoxicity. This is perhaps the first study
      on human skin cells demonstrating the cytotoxic and genotoxic potential of TiO(2)
      NPs.

PMID- 21092755
TI  - Chemical reactivity measurements: potential for characterization of respiratory
      chemical allergens.
AB  - Allergic diseases of the skin and respiratory tract resulting from exposure to
      low molecular weight chemicals remain important issues for consumer product
      development and occupational/environmental health. Widespread opportunities for
      exposure to chemical allergens require that there are available effective methods
      for hazard identification and risk assessment. In the search for new tools for
      hazard identification/characterization there has been interest in developing
      alternative methods that will reduce, refine or replace the need for animals. One
      approach that shows promise is based on the measurement of the peptide reactivity
      of chemicals; the potential to form stable associations with protein/peptide
      being a key requirement for the induction of sensitization. Recent investigations
      using these systems have focused primarily on skin sensitizing chemicals.
      However, there is interest in the possibility of exploiting these same
      experimental approaches to distinguish between different forms of chemical
      allergens - as individual materials are primarily associated with one or the
      other form of sensitization in humans. These investigations may also provide
      insight into why chemical sensitizers can differ in the form of allergic disease
      they will preferentially induce. These opportunities are surveyed here against a
      background of the immunobiology of allergic sensitization and current state-of
      the-art approaches to measurement of peptide/protein reactivity.

PMID- 21092757
TI  - Trans-4-oxo-2-nonenal potently alters mitochondrial function.
AB  - Alzheimer disease elevates lipid peroxidation in the brain and data indicate that
      the resulting lipid-aldehydes are pathological effectors of lipid peroxidation.
      The disposition of 4-substituted nonenals derived from arachidonate (20:4, n-6)
      and linoleate (18:2, n-6) oxidation is modulated by their protein adduction
      targets, their metabolism, and the nature of the 4-substitutent. Trans-4-oxo-2
      nonenal (4-ONE) has a higher toxicity in some systems than the more commonly
      studied trans-4-hydroxy-2-nonenal (HNE). In this work, we performed a structure
      function analysis of 4-hydroxy/oxoalkenal upon mitochondrial endpoints. We tested
      the hypotheses that 4-ONE, owing to a highly reactive nature, is more toxic than
      HNE and that HNE toxicity is enantioselective. We chose to study freshly isolated
      brain mitochondria because of the role of mitochondrial dysfunction in
      neurodegenerative disorders. Whereas there was little effect related to HNE
      chirality, our data indicate that in the mitochondrial environment, the order of
      toxic potency under most conditions was 4-ONE>HNE. 4-ONE uncoupled mitochondrial
      respiration at a concentration of 5MUM and inhibited aldehyde dehydrogenase 2
      (ALDH2) activity with an IC(50) of approximately 0.5MUM. The efficacy of altering
      mitochondrial endpoints was ALDH2 inhibition>respiration=mitochondrial
      swelling=ALDH5A inhibition>GSH depletion. Thiol-based alkenal scavengers, but not
      amine-based scavengers, were effective in blocking the effects of 4-ONE upon
      respiration. Quantum mechanical calculations provided insights into the basis for
      the elevated reactivity of 4-ONE>HNE. Our data demonstrate that 4-ONE is a potent
      effector of lipid peroxidation in the mitochondrial environment.

PMID- 21092756
TI  - The effects of aging on pulmonary oxidative damage, protein nitration, and
      extracellular superoxide dismutase down-regulation during systemic inflammation.
AB  - Systemic inflammatory response syndrome (SIRS), a serious clinical condition
      characterized by whole-body inflammation, is particularly threatening for elderly
      patients, who suffer much higher mortality rates than the young. A major
      pathological consequence of SIRS is acute lung injury caused by neutrophil
      mediated oxidative damage. Previously, we reported an increase in protein
      tyrosine nitration (a marker of oxidative/nitrosative damage) and a decrease in
      the antioxidant enzyme extracellular superoxide dismutase (EC-SOD) in the lungs
      of young mice during endotoxemia-induced SIRS. Here we demonstrate that during
      endotoxemia, down-regulation of EC-SOD is significantly more profound and
      prolonged, whereas up-regulation of iNOS is augmented, in aged compared to young
      mice. Aged mice also showed 2.5-fold higher protein nitration levels, compared to
      young mice, with particularly strong nitration in the pulmonary vascular
      endothelium during SIRS. Additionally, by two-dimensional gel electrophoresis,
      Western blotting, and mass spectrometry, we identified proteins that show
      increased tyrosine nitration in age- and SIRS-dependent manners; these proteins
      (profilin-1, transgelin-2, LASP 1, tropomyosin, and myosin) include components of
      the actin cytoskeleton responsible for maintaining pulmonary vascular
      permeability. Reduced EC-SOD in combination with increased oxidative/nitrosative
      damage and altered cytoskeletal protein function due to tyrosine nitration may
      contribute to augmented lung injury in the aged with SIRS.

PMID- 21092759
TI  - Chronic L-DOPA therapy alters central serotonergic function and L-DOPA-induced
      dopamine release in a region-dependent manner in a rat model of Parkinson's
      disease.
AB  - The therapeutic benefit of L-DOPA is commonly attributed to restoration of
      dopamine (DA) extracellular levels in the striatum of Parkinsonian patients.
      However, the loss of efficacy of L-DOPA after chronic use is paradoxically
      associated with a similar or enhanced striatal DA response. Release of L-DOPA
      derived DA depends on the widespread serotonergic (5-HT) innervation in the
      brain. Chronic exposure of 5-HT neurons to L-DOPA could lead to aberrant
      neurochemical responses beyond the striatum. Using multi-site intracerebral
      microdialysis in a rat model of Parkinson's disease, we showed that chronic L
      DOPA treatment at a therapeutic dose (12 mg/kg/day for 10 days) homogeneously
      reduced basal 5-HT release and metabolism. These effects were paralleled by a
      decrease in tissue content of 5-HT and its metabolite. Chronic L-DOPA treatment
      severely altered the brain pattern of 5-HT and DA release responses to L-DOPA (3
      12 mg/kg) with an overall loss of efficacy of L-DOPA to increase DA release. Our
      data demonstrate for the first time in vivo that the impairment of 5-HT neuronal
      function induced by chronic L-DOPA alters in a region-dependent manner L-DOPA
      induced DA release. Changes in neurochemical pattern of L-DOPA in the brain may
      favour the occurrence of both motor and non-motor side effects.

PMID- 21092760
TI  - Gastrojejunal stoma diameter predicts weight regain after Roux-en-Y gastric
      bypass.
AB  - BACKGROUND & AIMS: Weight regain after Roux-en-Y gastric bypass (RYGB) is
      associated with reductions in health status and quality of life. We evaluated
      whether gastrojejunal stoma diameter is a risk factor for weight regain after
      RYGB. METHODS: We examined data collected over 4 years from consecutive patients
      referred to a tertiary care bariatric center for upper endoscopy after RYGB. We
      used linear regression analysis to determine the association between the
      gastrojejunal stoma diameter and weight regain. We applied a logistic regression
      model using clinical and endoscopic parameters to develop a prediction rule for
      weight gain after RYGB. RESULTS: Among 165 patients included in our study, 59%
      had significant weight regain (>= 20% of maximum weight lost after the RYGB) and
      41% did not. The mean percentage of maximal weight lost after RYGB that was
      regained in the entire cohort was 30% +/- 22%. Gastrojejunal stoma diameter was
      associated significantly with weight regain after RYGB surgery in univariate
      analysis (beta = .31, P < .0001). This association remained significant after
      adjusting for several known or purported risk factors for weight regain (beta =
      .19, P = .003). We developed a simple prediction rule for weight regain after
      RYGB using a 7-point scoring system that includes the gastrojejunal stoma
      diameter, race, and percentage of maximal body weight lost after RYGB; a cut-off
      score of 4 or more points had an area under receiver operating characteristic
      curve of 0.76 and a positive predictive value of 75%. CONCLUSIONS: Increased
      gastrojejunal stoma diameter is a risk factor for weight regain after RYGB and
      can be incorporated in a novel prediction rule.

PMID- 21092758
TI  - CYP17 inhibitors for prostate cancer therapy.
AB  - Prostate cancer (PC) is now the second most prevalent cause of death in men in
      the USA and Europe. At present, the major treatment options include surgical or
      medical castration. These strategies cause ablation of the production of
      testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes.
      However, because these procedures do not affect adrenal, prostate and other
      tissues' androgen production, they are often combined with androgen receptor
      antagonists to block their action. Indeed, recent studies have unequivocally
      established that in castration-resistant prostate cancer (CRPC) many androgen
      regulated genes become re-expressed and tissue androgen levels increase despite
      low serum levels. Clearly, inhibition of the key enzyme which catalyzes the
      biosynthesis of androgens from pregnane precursors, 17alpha-hydroxy/17,20-lyase
      (hereafter referred to as CYP17) could prevent androgen production from all
      sources. Thus, total ablation of androgen production by potent CYP17 inhibitors
      may provide effective treatment of prostate cancer patients. This review
      highlights the role of androgen biosynthesis in the progression of prostate
      cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone
      acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical
      development. Article from the special issue on Targeted Inhibitors.

PMID- 21092761
TI  - Long-term outcome after antiviral therapy of patients with hepatitis C virus
      infection and decompensated cirrhosis.
AB  - BACKGROUND & AIMS: We evaluated the long-term outcomes after antiviral therapy of
      patients with decompensated cirrhosis and hepatitis C virus (HCV) infection.
      METHODS: Seventy-five patients with HCV infection and decompensated cirrhosis
      received therapy with peginterferon alfa-2b and ribavirin. We compared adverse
      event profiles and mortality rates between patients with or without sustained
      virologic responses (SVRs). The mean follow-up time off therapy was 51 +/- 18
      months (range, 3-78 months). RESULTS: Seven patients with HCV genotypes 1 or 4
      (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean
      survival times were 53 months among patients who did not achieve SVRs (95%
      confidence interval [CI], 48-59 months) and 73 months among those who did achieve
      SVRs (95% CI, 67-80 months) (P = .004). During the study, 25 patients died (2
      with and 23 without SVRs). During the follow-up period, 8 of 24 patients with
      SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of
      decompensation (P < .0001). The hospital readmission rates for patients with and
      without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5
      without/with SVR; 95% CI, 4.0-16.0; P < .0001). At the end of the follow-up
      period, the incidence of hepatocellular carcinoma was not associated with
      clearance of HCV. CONCLUSIONS: Among patients with cirrhosis that is a result of
      HCV infection and who have progressed to a stage of liver decompensation, an SVR
      after antiviral therapy is a positive prognostic factor.

PMID- 21092763
TI  - Small-bowel adenocarcinoma.

PMID- 21092762
TI  - Incidence and predictors of 30-day readmission among patients hospitalized for
      advanced liver disease.
AB  - BACKGROUND & AIMS: The rate of readmission to the hospital 30 days after
      discharge (30-day readmission rate) is used as a quality measure for hospitalized
      patients, but it has not been studied adequately for patients with advanced liver
      disease. We investigated the incidence and factors that predict this rate and its
      relationship with mortality at 90 days. METHODS: We analyzed data from patients
      with advanced liver disease who were hospitalized to an inpatient hepatology
      service at 2 large academic medical centers in 2008. Patients with elective
      admission and recipients of liver transplants were not included. During the study
      period, there were 447 patients and a total of 554 eligible admissions.
      Multivariate analyses were performed to identify variables associated with 30-day
      readmission and to examine its relationship with mortality at 90 days. RESULTS:
      The 30-day readmission rate was 20%. After adjusting for multiple covariates,
      readmission within 30 days was associated independently with model for end-stage
      liver disease scores at discharge (odds ratio [OR], 1.06; 95% confidence interval
      [CI], 1.02-1.09; P = .002), the presence of diabetes (OR, 1.78; 95% CI, 1.07
      2.95; P = .027), and male sex (OR, 1.73; 95% CI, 1.03-2.89; P = .038). After
      adjusting for age, sex, and model for end-stage liver disease score at discharge,
      the 90-day mortality rate was significantly higher among patients who were
      readmitted to the hospital within 30 days than those who were not (26.8% vs 9.8%;
      OR, 2.6; 95% CI, 1.36-5.02; P = .004). CONCLUSIONS: Patients with advanced liver
      disease frequently are readmitted to the hospital within 30 days after discharge;
      these patients have a higher 90-day mortality rate than those who are not
      readmitted in 30 days. These data might be used to develop strategies to reduce
      early readmission of hospitalized patients with cirrhosis.

PMID- 21092764
TI  - The Feeding Infants and Toddlers Study 2008: opportunities to assess parental,
      cultural, and environmental influences on dietary behaviors and obesity
      prevention among young children.

PMID- 21092765
TI  - The Feeding Infants and Toddlers Study 2008: study design and methods.
AB  - OBJECTIVE: Describe the study design, data collection methods, 24-hour dietary
      recall protocol, and sample characteristics of the Feeding Infants and Toddlers
      Study (FITS) 2008. DESIGN: A cross-sectional study designed to obtain information
      on the diets and feeding patterns of US infants, toddlers, and preschoolers ages
      birth to 47 months. Telephone interviews with parents and caregivers were
      conducted from June 2008 through January 2009 and included a household interview
      to recruit the household and collect information on household and child
      demographics and nutrition-related characteristics, and a dietary interview,
      including a 24-hour dietary recall collected using the 2008 Nutrition Data System
      for Research. A second dietary recall was collected on a random subsample to
      estimate usual nutrient intake distributions. Data collection instruments were
      built on those used in FITS 2002, with expanded survey content to address
      emerging issues in childhood nutrition and obesity. The dietary protocol was
      improved to increase reporting accuracy on portion sizes, and a bridging study
      was conducted to test effects of the changes in the food model booklet and
      protocol since FITS 2002 (n=240 cases aged 4 to 23 months). SUBJECTS: A national
      random sample of 3,273 infants, toddlers, and preschoolers from birth up to age 4
      years, with 2 days of dietary intake data for 701 cases. RESULTS: Among sampled
      households with an age-eligible child, the response rate was 60% for the
      recruitment interview. Of recruited households, the response rate for the dietary
      interview was 78%. CONCLUSIONS: The FITS 2008 provides rigorous, well-tested
      methods and survey questions for nutrition researchers to use in other dietary
      studies of young children. FITS 2008 findings on the food and nutrient intakes of
      US children from birth up to age 4 years can inform dietetics practitioners,
      pediatric health practitioners, and policymakers about the dietary issues of
      young children.

PMID- 21092766
TI  - Nutrient intakes of US infants, toddlers, and preschoolers meet or exceed dietary
      reference intakes.
AB  - OBJECTIVES: To assess the usual nutrient intakes of 3,273 US infants, toddlers,
      and preschoolers, aged 0 to 47 months, surveyed in the Feeding Infants and
      Toddlers Study (FITS) 2008; and to compare data on the usual nutrient intakes for
      the two waves of FITS conducted in 2002 and 2008. DESIGN: The FITS 2008 is a
      cross-sectional survey of a national random sample of US children from birth
      through age 47 months. Usual nutrient intakes derived from foods, beverages, and
      supplements were ascertained using a telephone-administered, multiple-pass 24
      hour dietary recall. SUBJECTS: Infants aged birth to 5 months (n=382) and 6 to 11
      months (n=505), toddlers aged 12 to 23 months (n=925), and preschoolers aged 24
      to 47 months (n=1,461) were surveyed. METHODS: All primary caregivers completed
      one 24-hour dietary recall and a random subsample (n=701) completed a second 24
      hour dietary recall. The personal computer version of the Software for Intake
      Distribution Estimation was used to estimate the 10th, 25th, 50th, 75th, and 90th
      percentiles, as well as the proportions below and above cutoff values defined by
      the Dietary Reference Intakes or the 2005 Dietary Guidelines for Americans.
      RESULTS: Usual nutrient intakes met or exceeded energy and protein requirements
      with minimal risk of vitamin and mineral deficiencies. The usual intakes of
      antioxidants, B vitamins, bone-related nutrients, and other micronutrients were
      adequate relative to the Adequate Intakes or Estimated Average Requirements,
      except for iron and zinc in a small subset of older infants, and vitamin E and
      potassium in toddlers and preschoolers. Intakes of synthetic folate, preformed
      vitamin A, zinc, and sodium exceeded Tolerable Upper Intake Level in a
      significant proportion of toddlers and preschoolers. Macronutrient distributions
      were within acceptable macronutrient distribution ranges, except for dietary fat,
      in some toddlers and preschoolers. Dietary fiber was low in the vast majority of
      toddlers and preschoolers, and saturated fat intakes exceeded recommendations for
      the majority of preschoolers. The prevalence of inadequate intakes, excessive
      intake, and intakes outside the acceptable macronutrient distribution range was
      similar in FITS 2002 and FITS 2008. CONCLUSIONS: In FITS 2008, usual nutrient
      intakes were adequate for the majority of US infants, toddlers, and preschoolers,
      except for a small but important number of infants at risk for inadequate iron
      and zinc intakes. Diet quality should be improved in the transition from infancy
      to early childhood, particularly with respect to healthier fats and fiber in the
      diets of toddlers and preschoolers.

PMID- 21092768
TI  - New findings from the Feeding Infants and Toddlers Study: data to inform action.

PMID- 21092767
TI  - Food consumption patterns of infants and toddlers: where are we now?
AB  - OBJECTIVES: To describe current infant-feeding practices and current food group
      consumption patterns of infants and toddlers and to compare 2008 data with 2002
      data to identify shifts in these practices and food consumption over time.
      DESIGN: The Feeding Infants and Toddlers Study (FITS) 2008 is a cross-sectional
      survey of a national random sample of US children from birth up to age 4 years.
      Data for three age subgroups (infants 4 to 5.9 months and 6 to 11.9 months and
      toddlers 12 to 23.9 months) were used from the 2002 (n=2,884) and 2008 surveys
      (n=1,596). STATISTICAL METHODS: All analyses use sample weights that reflect the
      US population aged 4 to 24 months. Descriptive statistics (means, proportions,
      and standard errors) and t tests were calculated using SUDAAN (release 9, 2005,
      Research Triangle Park Institute, Research Triangle Park, NC). RESULTS: These
      data show a higher percentage of infants receiving breast milk from 4 to 11.9
      months of age with a concurrent decreasing percentage of infants receiving
      formula, which is significantly different from data for the 9- to 11.9-month-old
      age group. The use of complementary foods also appears to be delayed in FITS
      2008: There is a significantly lower proportion of infants consuming infant
      cereal at 9 to 11.9 months in FITS 2008 compared to 2002 data. Fruit and
      vegetable consumption remains lower than desired. Significant reductions in the
      percentage of infants and toddlers consuming any desserts or candy, sweetened
      beverages, and salty snacks were seen in 2008. CONCLUSIONS: The findings
      presented here provide important insights to the content of messages and types of
      interventions that are still needed to improve the diets of infants and toddlers.

PMID- 21092769
TI  - Food consumption patterns of young preschoolers: are they starting off on the
      right path?
AB  - OBJECTIVE: To describe the food consumption patterns of US children aged 2 and 3
      years. DESIGN: Descriptive analysis of data collected in the Feeding Infants and
      Toddlers Study 2008 based on a single 24-hour dietary recall collected by
      telephone. SUBJECTS: A national random sample of children aged 2 and 3 years
      (n=1,461). STATISTICAL ANALYSES PERFORMED: The percentage of children consuming
      foods from specific food groups was estimated for the full sample of children
      aged 2 and 3 years and separately by year of age. RESULTS: About a third of 2
      year-olds and a quarter of 3-year-olds consumed whole milk at least once in a
      day. About 70% of 2- and 3-year-olds consumed vegetables as a distinct food item
      at least once in day. French fries and other fried potatoes were the most
      commonly consumed vegetable. Almost three quarters of children (73%) consumed
      fruit as a distinct food item at least once in a day, and 59% consumed 100%
      juice. Fresh fruit was the most commonly consumed type of fruit. About 85% of
      children consumed some type of sweetened beverage, dessert, sweet, or salty snack
      in a day. Percentages of children consuming such foods were consistently higher
      for 3-year-olds than for 2-year-olds. CONCLUSIONS: Parents and caregivers should
      be encouraged to expose young children to a wide variety of fruits and
      vegetables, whole grains, low-fat dairy products, and healthier fats, and to
      limit consumption of low-nutrient, energy-dense foods and beverages. Dietary
      guidance should stress the fact that children in this age group have high
      nutrient needs and relatively low energy requirements, leaving little room for
      such foods. Parents need advice that is specific, practical, and actionable.

PMID- 21092770
TI  - Feeding Infants and Toddlers Study 2008: progress, continuing concerns, and
      implications.

PMID- 21092771
TI  - The fitness of FITS.

PMID- 21092772
TI  - Introduction. The treatment of diseases of the aorta.

PMID- 21092773
TI  - Percutaneous aortic valves: effective in inoperable patients, what price in high
      risk patients?

PMID- 21092774
TI  - Strategies for subacute/chronic type B aortic dissection: the Investigation Of
      Stent Grafts in Patients with type B Aortic Dissection (INSTEAD) trial 1-year
      outcome.
AB  - OBJECTIVE: Endovascular stent grafting represents a novel concept for type B
      aortic dissection both in the acute and subacute/chronic setting, with an unknown
      effect on outcomes. METHODS: In a prospective trial 140 patients with stable type
      B dissection were randomly subjected to elective stent-graft placement in
      addition to optimal medical therapy (n = 72) or to optimal medical therapy (n =
      68) with surveillance (arterial pressure according to World Health Organization
      guidelines <= 120/80 mm Hg). The primary end point was 1-year all-cause
      mortality, whereas aorta-related mortality, progression (with need for conversion
      or additional endovascular or open surgical intervention), and aortic remodeling
      were secondary end points. RESULTS: There was no difference in all-cause
      mortality: cumulative survival was 97.0% +/- 3.4% with optimal medical therapy
      versus 91.3% +/- 2.1% with thoracic endovascular aortic repair (P = .16).
      Moreover, aorta-related mortality was not different (P = .42), and the risk for
      the combined end point of aorta-related death (rupture) and progression
      (including conversion or additional endovascular or open surgical intervention)
      was similar (P = .86). Three neurologic adverse events occurred in the thoracic
      endovascular aortic repair group (1 paraplegia, 1 stroke, and 1 transient
      paraparesis) versus 1 episode of paraparesis with medical treatment. Finally,
      aortic remodeling (with true-lumen recovery and thoracic false-lumen thrombosis)
      occurred in 91.3% with thoracic endovascular aortic repair versus 19.4% with
      medical treatment (P < .001), which is suggestive of continued remodeling.
      CONCLUSIONS: In survivors of uncomplicated type B aortic dissection, elective
      stent-graft placement does not improve 1-year survival and adverse events,
      despite favorable aortic remodeling.

PMID- 21092775
TI  - Thoracic endovascular aortic repair for acute complicated type B aortic
      dissection: superiority relative to conventional open surgical and medical
      therapy.
AB  - OBJECTIVE: This study compared outcomes between thoracic endovascular aortic
      repair and conventional open surgical and medical therapies for acute complicated
      type B aortic dissection. METHODS: From 2002 to 2010, a total of 170 patients
      with type B aortic dissections were retrospectively identified from the
      University of Pennsylvania aortic database. Of these 170 patients, 147 had acute
      type B aortic dissections (uncomplicated 70, complicated 77). For patients with
      acute complicated type B aortic dissections, management included thoracic
      endovascular aortic repair (group A) or conventional open surgical and medical
      therapies (group B). RESULTS: In the 77 patients with acute complicated type B
      aortic dissections, thoracic endovascular aortic repair (group A) was performed
      in 45 patients (59%). In group B, 20 patients (26%) underwent open surgical
      repair and 12 (15%) had their conditions managed with medical therapy. Thoracic
      endovascular aortic repair was associated with lower in-hospital or 30-day
      mortality (n = 2, 4%) than conventional therapy (open surgical repair n = 8, 40%,
      medical therapy, n = 4, 33%, P = .006). Patients in group A (thoracic
      endovascular aortic repair) continued to show significantly improved survival at
      1, 3, and 5 years (group A: 82%, 79%, and 79% vs group B: 58%, 52%, and 44%, P =
      .008). CONCLUSIONS: Thoracic endovascular aortic repair for acute complicated
      type B dissection is associated with superior early outcome and improved midterm
      survival relative to conventional therapy. Longer follow-up demonstrating
      survival benefit is needed before definitive conclusion can be made.

PMID- 21092776
TI  - Multicenter early experience with extended aortic repair in acute aortic
      dissection: is simultaneous descending stent grafting justified?
AB  - OBJECTIVE: In acute type A aortic dissection, the extension of repair to
      downstream aorta has been controversially discussed. We present the early results
      of a multicenter study using a hybrid stent graft prosthesis. METHODS: Between
      January 2005 and January 2010, the data from 191 patients after combined proximal
      aortic replacement and antegrade stent grafting were collected in the database of
      the International E-vita open Registry. Of the 191 patients, 68 underwent surgery
      for acute aortic dissection and were included in the present study. Hypothermic
      circulatory arrest and selective cerebral perfusion were routinely used. Computed
      aortic imaging was performed for false lumen evaluation during follow-up.
      RESULTS: The in-hospital mortality rate was 13% (9/68). Along the stent graft,
      the rate of immediate complete false lumen thrombosis was 86% (51/59) and
      increased during follow-up (23 +/- 17 months) to 94% (46/49). Distally, complete
      or partial false lumen thrombosis was initially observed in 61% (36/59) and in
      82% (40/49) after follow-up. The 1- and 3-year actuarial survival rate was 82%
      and 74%, respectively. CONCLUSIONS: Extended thoracic aortic repair of acute
      aortic dissection with a hybrid stent graft is feasible at acceptable early
      mortality and promotes false lumen thrombosis around the stent graft and below.

PMID- 21092777
TI  - Indications for thoracoabdominal aortic surgery.

PMID- 21092778
TI  - Measuring the collateral network pressure to minimize paraplegia risk in
      thoracoabdominal aneurysm resection.
AB  - OBJECTIVE: To minimize paraplegia during thoracoabdominal aortic aneurysm repair,
      the concept of the collateral network was developed. That is, spinal cord
      perfusion is provided by an interconnecting complex of vessels in the
      intraspinal, paraspinous, and epidural space and in the paravertebral muscles,
      including intercostal and lumbar segmental as well as subclavian and hypogastric
      arteries. METHODS: Collateral network pressure was measured with a catheter in
      the distal end of a ligated segmental artery in pigs and human beings. RESULTS:
      In the pig, collateral network pressure was 75% of the simultaneous mean aortic
      pressure. With complete segmental arterial ligation, it fell to 27% of baseline,
      recovering to 40% at 24 hours and 90% at 120 hours. Spinal cord injury occurred
      in approximately 50% of animals. When all segmental arteries were taken in 2
      stages a week apart, collateral network pressure fell only to 50% to 70% of
      baseline, and spinal cord injury was rare. In human beings, baseline collateral
      network pressure also was 75% of mean aortic pressure, fell in proportion to the
      number of segmental arteries ligated, and began recovery within 24 hours.
      Collateral network pressure was lower with nonpulsatile distal bypass than with
      pulsatile perfusion. CONCLUSIONS: After subtraction of a measure of spinal cord
      outflow pressure (cerebrospinal fluid pressure or central venous pressure),
      collateral network pressure provides a clinically useful estimate of spinal cord
      perfusion pressure.

PMID- 21092779
TI  - Neuromonitor-guided repair of thoracoabdominal aortic aneurysms.
AB  - OBJECTIVE: Monitoring during thoracoabdominal aortic aneurysm repair has included
      the use of cerebrospinal fluid drainage and motor and somatosensory evoked
      potentials. We report our experience with neuromonitoring-guided thoracoabdominal
      aortic aneurysm repair. METHODS: Between November 2008 and January 2010, 105
      thoracic aorta repairs were performed; 89% of patients (93/105) underwent repair
      using cerebrospinal fluid drainage and distal aortic perfusion. In addition,
      somatosensory and motor evoked potentials were monitored during repair, and
      active intraoperative maneuvers were undertaken in response to changes in the
      signals. Intraoperative maneuvers included intercostal artery reimplantation.
      RESULTS: In-hospital mortality for thoracic and thoracoabdominal aortic repair
      was 5.7% (6/105). Immediate spinal cord injury occurred in 1 patient (1%), and 3
      patients (3%) had delayed neurologic deficit. Intercostal arteries were
      reattached in 85% of possible cases (51/60). Somatosensory evoked potentials
      achieved adequate readings in 99% of cases (102/103). Loss of somatosensory
      evoked potential was encountered in 26% of cases (27/102), and return of
      somatosensory evoked potentials occurred in all cases after intraoperative
      maneuvers. Motor evoked potentials achieved adequate readings in 96% of cases
      (99/103). Loss of motor evoked potential was encountered in 50% of cases (50/99),
      and return of motor evoked potentials occurred in all but 1 case (95%). This
      patient awoke with an immediate spinal neurologic deficit. CONCLUSIONS:
      Neuromonitoring using somatosensory evoked potentials and motor evoked potentials
      seems useful during thoracoabdominal aortic aneurysm repair. Alterations in
      intraoperative conduct resulted in return of neuromonitoring signals. This
      suggests a benefit in intercostal artery reimplantation via increasing perfusion
      to the collateral network of the spinal cord. Further studies using
      neuromonitoring-guided repair of thoracoabdominal aortic aneurysms are warranted.

PMID- 21092780
TI  - It is not just assisted circulation, hypothermic arrest, or clamp and sew.
AB  - We have surgically treated 771 patients for thoracic and thoracoabdominal aortic
      aneurysms since 1983. Our primary effort has been to develop experimentally
      validated strategies to reduce paraplegia, renal failure, and mortality in these
      high-risk patients. This approach has led to a spinal cord protection protocol
      that has reduced paraplegia risk by 80% (observed/expected ratio = 0.19) with the
      use of cerebral spinal fluid drainage, moderate hypothermia (31 degrees C-33
      degrees C), endorphin receptor antagonist (naloxone), and thiopental burst
      suppression while optimizing mean arterial pressure (> 90 mm Hg) and cardiac
      index. The elective mortality rate is 2.80% (17% for acute patients), and with
      rapid renal cooling for renal protection, only 0.88% required permanent dialysis.
      These results were achieved without the use of assisted circulation. We have
      reattached intercostal arteries since 2005 using preoperative magnetic resonance
      angiographic localization, but it remains unclear whether intercostal
      reimplantation reduces paraplegia risk, as we had initially proposed. We strongly
      believe that a consistent anesthetic and postoperative care protocol uniformly
      built and applied around these principles greatly enhances our surgical outcomes.
      We also show that improved outcomes with assisted circulation and hypothermic
      arrest in treatment of thoracoabdominal aortic disease follow similar principles
      of spinal cord and end-organ protection.

PMID- 21092781
TI  - Aortic root aneurysm: principles of repair and long-term follow-up.
AB  - OBJECTIVES: This study was undertaken to examine clinical and echocardiographic
      outcomes of aortic valve-sparing operations to treat aortic root aneurysms.
      METHODS: From May 1988 to December 2007, a total of 228 patients underwent
      reimplantation of the aortic valve, and 61 underwent remodeling of the aortic
      root. Patients were followed up prospectively and had echocardiographic
      evaluation of valve function. Mean follow-up was 7.28 +/- 4.33 years. RESULTS:
      There were 5 operative and 26 late deaths. Survival at 12 years was 82.9 +/- 3.7%
      and similar between types of operations. Age and aortic dissection were
      independent predictors of mortality. Seven patients have had reoperations on the
      aortic valve: 6 for aortic insufficiency and 1 for endocarditis. Five of these
      patients had undergone remodeling of the aortic root. Freedoms from reoperation
      at 12 years were 94.3% +/- 2.6% among all patients, 90.4% +/- 4.7% after
      remodeling, and 97.4% +/- 2.2% after reimplantation (P = .09). Postoperatively,
      moderate aortic insufficiency developed in 14 patients (8 remodeling and 6
      reimplantation) and severe aortic insufficiency in 5 (3 remodeling and 2
      reimplantation). The remaining patients had mild, trace, or no aortic
      insufficiency. Freedoms from moderate or severe aortic insufficiency at 12 years
      were 86.8% +/- 3.8% among all patients, 82.6% +/- 6.2% after remodeling, and
      91.0% +/- 3.8% after reimplantation (P = .035). Only age-by 5-year increments-was
      an independent predictor of postoperative aortic insufficiency. CONCLUSIONS:
      Aortic valve-sparing operations provide excellent patient survival and stable
      aortic valve function, particularly after reimplantation of the aortic valve.

PMID- 21092783
TI  - Strategies for renal and visceral protection in thoracoabdominal aortic surgery.

PMID- 21092784
TI  - One-stage repair of extensive thoracic aortic disease.
AB  - OBJECTIVE: Staged procedures for extensive aneurysmal disease of the thoracic
      aorta are associated with substantial cumulative mortality for the 2 procedures
      and death in the interval in between, often from aortic rupture. We have used a 1
      stage procedure for operative repair of most, or all, of the thoracic aorta.
      METHODS: Ninety-five patients were treated using a bilateral anterior thoracotomy
      with transverse sternotomy, hypothermic circulatory arrest, and reperfusion of
      the arch vessels first to minimize brain ischemia. Fifty-six patients had chronic
      type A aortic dissections (all but 2 patients had a previous operation), 36
      patients had degenerative aneurysms, and 3 patients had chronic type B aortic
      dissections with proximal extension. The ascending aorta and aortic arch were
      replaced in all patients combined with resection of varying lengths of descending
      aorta. RESULTS: In-hospital mortality was 8.4% (8 patients). Morbidity included
      reoperation for bleeding (11%), mechanical ventilation for more than 72 hours
      (48%), tracheostomy (17%), and renal dialysis (8%). Stroke occurred in 1 patient
      (1%). Seven of the 93 operative survivors (7.6%) have undergone successful
      reoperation on the graft (4 patients) or the contiguous aorta (3 patients).
      CONCLUSIONS: The 1-stage, arch-first technique is a safe and suitable alternative
      to 2-stage procedures for repair of thoracic aortic disease. Its effectiveness
      relative to more recently developed hybrid procedures awaits further analysis of
      long-term performance.

PMID- 21092785
TI  - Early and late results of descending thoracic and thoracoabdominal aortic
      aneurysm open repair with deep hypothermia and circulatory arrest.
AB  - OBJECTIVE: Open repair of descending thoracic aortic and thoracoabdominal aortic
      aneurysms may carry low morbidity and mortality, depending on experience of the
      surgeon and operative technique used. Although thoracic endovascular aortic
      repair is less invasive, its limitations include anatomy and pathology of the
      aorta, proximity of major branches, and significant complication and
      reintervention rates. We retrospectively reviewed a 2-surgeon experience (J.W.F.
      and J.S.C.) with deep hypothermic circulatory arrest to repair descending
      thoracic aortic and thoracoabdominal aortic aneurysms. METHODS: All patients (n =
      343) who underwent surgical replacement of descending thoracic aortic or
      thoracoabdominal aortic aneurysm with deep hypothermic circulatory arrest from
      1995 to 2009 were included. Segmental arteries between T8 and the celiac artery
      were aggressively reimplanted as indicated. Visceral and renal artery bypasses
      were performed for significant stenosis. Concomitant coronary artery bypass
      grafting was performed if targets were anterior or lateral wall vessels. Lumbar
      drains were not routinely used but placed postoperatively on clinical evidence of
      spinal cord ischemia. RESULTS: Of 343 patients, 98 had descending thoracic aortic
      aneurysms, 69 had Crawford type I thoracoabdominal aortic aneurysms, 111 had type
      II, 32 had type III, and 33 had type IV. Emergency or urgent operations comprised
      13% of repairs. Hospital mortalities were 5.0% for all cases, 3.7% for elective
      cases, and 13.3% for urgent or emergency cases. Overall incidences were 4.4% for
      stroke, 3.2% for paraplegia or paraparesis, 1.5% for renal failure requiring
      dialysis, and 3.5% for tracheostomy. The 1-, 3-, 5-, and 10-year survival rates
      were 90%, 79%, 69%, and 54%, respectively. CONCLUSIONS: Surgical repair of
      descending thoracic aortic and thoracoabdominal aortic aneurysms with deep
      hypothermic circulatory arrest carries low operative morbidity and mortality and
      excellent early and late survival rates. These results can be used as a benchmark
      for future techniques and technologies.

PMID- 21092786
TI  - Incidence and risk factors of renal dysfunction after thoracic endovascular
      aortic repair.
AB  - OBJECTIVES: The risk of renal failure after thoracic endovascular aortic repair
      is not widely established. The aim of this study was to assess the incidence and
      risk factors of renal failure. METHODS: Between 1998 and 2008, 175 consecutive
      patients underwent 210 procedures at 2 tertiary academic institutions. Similar
      nephroprotective protocols and intravascular ultrasound were used. Retrospective
      analysis was performed. Generalized linear model was used to identify factors
      associated with change in postoperative estimated glomerular filtration rate.
      RESULTS: Underlying aortic diseases included 103 aneurysms, 72 dissections, 21
      transections, and 14 penetrating ulcers. Median preoperative estimated glomerular
      filtration rate was 65 mL . min(-1) . 1.73 m(-2). Contrast media averaged 108.7
      +/- 69.8 mL. Median estimated glomerular filtration rates within 48 hours and 30
      days were 69 and 67 mL . min(-1) . 1.73 m(-2), respectively. Rates of acute renal
      dysfunction risk (>25% estimated glomerular filtration rate decrease), acute
      kidney injury (>50% estimated glomerular filtration rate decrease), acute kidney
      function failure (>75% estimated glomerular filtration rate decrease), and
      hemodialysis were 9.8% (19/193), 1.6% (3/193), 0% (0/193), and 0.5% (1/193),
      respectively. Rates of renal dysfunction at 1 month and 6 months were 13.3%
      (10/75) and 17.7% (6/34), respectively. Risk factors for acute renal dysfunction
      were intraoperative hypotension, stroke, sepsis, lengthy procedures, and number
      of stents; at 1 and 6 months they were increased age, male gender, African
      American race, diabetes mellitus, chronic pulmonary disease, smoking, and zone 0
      to 1 graft deployment. Obesity was nephroprotective. CONCLUSIONS: Thoracic aortic
      endograft has a significant rate of renal dysfunction; however, it is lower in
      this cohort than in previous smaller series. Routine use of intravascular
      ultrasound and reduced contrast may have contributed to lower rates of renal
      insufficiency.

PMID- 21092787
TI  - Hybrid and endovascular therapy for extensive thoracoabdominal aortic disease.
AB  - The past 4 decades have witnessed tremendous strides in the evolution of
      endovascular technology with increased operator experience, greater availability
      of more sophisticated and versatile endovascular devices, and advances in imaging
      modalities. In an attempt to limit the physiologic derangements associated with
      aortic crossclamping and extensive tissue dissection during traditional open
      surgical repair of extensive thoracoabdominal aortic aneurysms, less invasive
      strategies have been explored using endovascular technology: hybrid approaches
      and solely endovascular techniques. This article describes these techniques and
      their advantages, their current role in thoracoabdominal aortic aneurysm repair
      and potential future developments in this field.

PMID- 21092788
TI  - Branched endografts for thoracoabdominal aneurysms.
AB  - PURPOSE: Endovascular management of thoracoabdominal aneurysms has been studied
      since 2001, with marked advances allowing for the treatment of complex anatomic
      situations including chronic aortic dissections, tortuous anatomy, and extensive
      aneurysms that involve the visceral segment, aortic arch, and iliacs as well.
      However, the technology is not widely disseminated, and a thorough understanding
      of the engineering principles, imaging techniques, and devices available is
      required. METHODS: Reinforced fenestrated branches coupled with balloon
      expandable stent grafts, and side-arm branch designs mated with self-expanding
      stent grafts have been used. Pure fenestrated designs were used for juxtarenal
      aneurysms, whereas thoracoabdominal aneurysms were treated with reinforced
      fenestrated branches or hybrid devices including side-arm branches and reinforced
      fenestrated branches. Intraoperative fusion techniques have been used since 2009,
      whereby preoperative computed tomographic data are fused with intraoperative
      fluoroscopy. Long-term survival in accordance with extent of disease was assessed
      with life table analysis techniques, and differences were analyzed using the log
      rank test. Intermediate-term data pertaining to patency related to both types of
      branches and paraplegia have been evaluated and previously published. RESULTS: A
      total of 406 patients with thoracoabdominal aneurysms and 227 patients with
      juxtarenal aneurysms have been enrolled in a prospective study. Perioperative and
      2-year survival were most closely related to extent of initial disease and were
      estimated to be 1.8% and 82% for juxtarenal aneurysms, 2.3% and 82% for type IV,
      and 5.2% and 74% for type II and III thoracoabdominal aneurysms at 24 months,
      respectively. When patients undergoing endovascular repair (ER group) were
      matched with those having contemporary surgical repair (SR group) for anatomic
      disease extent, mortality was similar at 30 days (5.7% ER vs 8.3% SR; P = .2) and
      at 12 months (15.6% ER vs 15.9% SR; P = .9). Paraplegia risk was also similar
      between the 2 groups (4.3% ER vs 7.5% SR, respectively; P = .08). Among the 633
      patients, there were 5 (0.8%) late ruptures at a mean of 18 months after
      treatment, of which 4 were fatal. They were attributed to component separation (n
      = 3), a remote aneurysm rupture proximal to the endovascular repair, and a failed
      surgical polyester graft distal to the repair. Reinforced fenestrated branch
      patency, when coupled with balloon-expandable stent grafts, was 97.8% at a mean
      follow-up of 15 months. Side-arm branch occlusion occurred in only 1 case, within
      24 hours of the procedure. New imaging tools resulted in a marked reduction in
      the average contrast dose (>50%). CONCLUSIONS: Intermediate-term results with
      multiple methods of endovascular repair of thoracoabdominal aneurysm indicate the
      technical feasibility of the procedure and show great promise in patients
      considered at high risk for open surgery. The intermediate-term patency and
      survival are excellent, and ruptures are exceedingly uncommon. However, mortality
      and spinal cord ischemia risks are still considerable with this technique.

PMID- 21092790
TI  - Treatment guidelines for thoracic aortic aneurysms and dissections based on the
      underlying causative gene.

PMID- 21092791
TI  - Principles of aortic valve repair.

PMID- 21092792
TI  - Use of the Valsalva graft and long-term follow-up.
AB  - OBJECTIVE: The Valsalva graft is a specifically designed Dacron graft that, on
      implantation and pressurization, generates pseudosinuses of Valsalva. We reviewed
      a multicenter experience of the reimplantation procedure with the Valsalva graft
      in patients with aneurysms involving the aortic root. METHODS: A total of 278
      patients underwent valve-sparing aortic root replacement using the Valsalva graft
      at 4 different Italian cardiac surgery centers and were studied by clinical
      assessment and echocardiography. Of the 278 patients, 220 were men (79%), with a
      mean age of 56 +/- 15 years. Of the patients, 42 (15%) had Marfan syndrome, 31
      (11%) had a bicuspid aortic valve, 13 (5%) had acute aortic dissection, and 136
      (49%) had grade 3 or 4+ aortic insufficiency. Concomitant cardiac procedures were
      performed in 78 patients (28%). Additional aortic leaflet repair was necessary in
      25 patients (9%). The mean crossclamp time was 120 +/- 27 minutes. RESULTS: There
      were 5 (1.8%) operative and 5 (1.8%) late deaths. The mean follow-up was 52 +/-
      28 months (range, 2-112 months) and was 100% complete. The cumulative actuarial
      survival was 95.2% (268 patients). A total of 32 patients (11%) had grade 3 to 4+
      aortic insufficiency, and 17 of these required late aortic valve replacement
      (range, 3-78 months). At 10 years of follow-up, the freedom from aortic valve
      reoperation rate was 91%, and the rate of freedom from residual aortic
      insufficiency not needing reoperation was 88%. CONCLUSIONS: The reimplantation
      type of valve-sparing procedure can be facilitated by the use of the Valsalva
      graft and can be performed with satisfactory perioperative and midterm results.
      How an optimal root reconstruction will affect the second decade of follow-up has
      yet to be determined.

PMID- 21092793
TI  - An aortic ring: from physiologic reconstruction of the root to a standardized
      approach for aortic valve repair.
AB  - OBJECTIVE: We suggest standardizing aortic valve repair using a physiologic
      approach by associating root remodeling with resuspension of the cusp effective
      height and external subvalvular aortic ring annuloplasty. METHODS: A total of 187
      patients underwent remodeling associated with subvalvular aortic ring
      annuloplasty (14 centers, 24 surgeons). Three strategies for cusp repair were
      evaluated: group 1, gross visual estimation (74 patients); group 2, alignment of
      cusp free edges (62 patients); and group 3, 2-step approach, alignment of the
      cusp free edges and effective height resuspension (51 patients). The composite
      outcome was defined as recurrence of aortic insufficiency of grade 2 or greater
      and/or reoperation. RESULTS: The operative mortality rate was 3.2% (n = 6).
      Treatment of a cusp lesion was most frequently performed in group 3 (70.6% vs
      20.3% in group 1 and 30.6% in group 2, P < .001). Nine patients required
      reoperation during a follow-up period of 24 months (range, 12-45), 6 patients in
      group 1 and 3 patients in group 2. At 1 year, no patients in group 3 presented
      with composite outcome events compared with 28.1% in group 1 and 15% in group 2
      (P < .001). Residual aortic insufficiency and tricuspid anatomy were independent
      risk factors for the composite outcome in groups 1 and 2. The annulus diameter,
      the presence of Marfan syndrome, and cusp repair had no effect on aortic
      insufficiency recurrence or reoperation. CONCLUSIONS: A standardized and
      physiologic approach to aortic valve repair, considering both the aorta (root
      remodeling) and the valve (resuspension of the cusp effective height and
      subvalvular ring annuloplasty) improved the preliminary results and might affect
      their long-term durability. The ongoing Conservative Aortic Valve Surgery for
      Aortic Insufficiency and Aneurysm of the Aortic Root (CAVIAAR) trial will compare
      this strategy to mechanical valve replacement.

PMID- 21092794
TI  - Valve-preserving root replacement in bicuspid aortic valves.
AB  - OBJECTIVE: Bicuspid aortic valve anatomy is associated with aortic root aneurysm
      in a relevant proportion of patients. These patients require root replacement for
      prognostic reasons, and the valve may be preserved. The objective of this
      analysis is to analyze the early and late outcomes of root remodeling for
      bicuspid aortic valve. METHODS: Between November 1995 and December 2009, 153
      patients (133 male) were treated by root remodeling in the presence of a bicuspid
      aortic valve. Acute dissection was present in 6 individuals. In 137 instances,
      additional correction of cusp pathology was achieved by plication (n = 119),
      triangular resection (n = 59), and implantation of a pericardial patch (n = 27).
      Follow-up ranges from 3 months to 14.5 years (mean, 4.9 +/- 3.8 years;
      cumulative, 757 years) and is complete in 99.3%. RESULTS: One patient died of
      intracranial hemorrhage in the hospital (mortality 0.7%). Survival at 5 and 10
      years was 99% and 91%, respectively. Seven patients required reoperation for
      stenosis (n = 1) or recurrent aortic insufficiency (n = 6) between 1 month and 11
      years postoperatively. The aortic valve was re-repaired in 2 cases. Freedom from
      reoperation at 5 and 10 years was 95%; freedom from valve replacement was 97%.
      Freedom from valve-related complications was 91% at 5 and 10 years. CONCLUSIONS:
      Root remodeling for aortic root aneurysm in the presence of a bicuspid aortic
      valve can be performed with a low morbidity and mortality. The long-term
      stability of the reconstructed aortic valve is excellent if normal valve
      configuration is achieved. The occurrence of late stenosis seems to be rare, and
      freedom from valve-related complications is high.

PMID- 21092795
TI  - Replacement of the ascending aorta in bicuspid aortic valve disease: where do we
      draw the line?

PMID- 21092797
TI  - Indications for aortic replacement.
AB  - This monograph reviews currently accepted criteria for extirpation of the
      aneurysmal thoracic aorta. Presence of symptoms suffices to justify resection
      regardless of size. For asymptomatic patients, resection of the ascending aorta
      at 5 to 5.5 cm is warranted. The descending aorta can be watched until slightly
      larger sizes (ie, 5.5-6 cm). Marfan disease or bicuspid aortic valve encourages
      resection in the smaller region of these size ranges. A nomogram permits
      adjustment of intervention criteria for extremes of body size. A recently
      computerized aortic risk calculator automatically applies exponential equations
      for determination of yearly risk of rupture or dissection for individual patients
      (available at: http://aorta.yale.edu). Evolving modalities to enhance decision
      making include positron emission tomography imaging of aneurysm metabolic
      activity, measurement of mechanical properties of the aorta by echocardiography,
      and assessment of the biomolecular state of the aneurysm with the "RNA Signature"
      test.

PMID- 21092798
TI  - Does the dilated ascending aorta in an adult with congenital heart disease
      require intervention?
AB  - OBJECTIVES: There is increasing attention to prophylactic replacement of the
      moderately dilated ascending aorta at aortic valve surgery. Moderate ascending
      aortic dilatation is common in adult patients with conotruncal anomalies. There
      are no data outlining actual risk of progressive ascending aortic dilatation or
      dissection to provide management guidelines. METHODS: From December 1973 through
      January 2008, 81 consecutive adults (median age, 34 years; range, 18--59 years)
      with conotruncal anomalies underwent operation on the aortic root, ascending
      aorta, or aortic valve. Primary cardiac diagnoses included tetralogy of Fallot
      with or without pulmonary atresia in 60 patients, truncus arteriosus in 12,
      double-outlet right ventricle in 6, and other in 3. Indications for operation
      included aortic regurgitation in 69 patients, supracoronary ascending aneurysm in
      16, aortic stenosis in 5, and other in 8. Median ascending aortic size was 45 mm
      (23--80 mm). RESULTS: Operations included isolated aortic valve
      repair/replacement in 63 patients, combined aortic valve replacement and
      reduction aortoplasty in 9, aortic root replacement in 7, and isolated ascending
      aortic replacement in 2. Four patients required reoperation during a median
      follow-up of 3.8 years (maximum 31 years). There were no ascending aortic
      reoperations after previous reduction aortoplasties or supracoronary ascending
      aortic grafts, and there were no late aortic dissections. CONCLUSIONS: Moderate
      ascending aortic enlargement is common among patients with conotruncal anomalies
      coming to operation, but aortic dissection is rare, as is subsequent need for
      aortic reoperation. Despite current enthusiasm for prophylactic operations on the
      ascending aorta in patients with acquired disease, these data suggest that the
      moderately dilated aorta in this setting may be observed.

PMID- 21092799
TI  - Aortic root reoperations after pulmonary autograft implantation.
AB  - OBJECTIVE: To report the results of aortic root reoperations after pulmonary
      autograft implantation. METHODS: All consecutive patients in our prospective Ross
      research database were selected for analysis, and additional information for
      patients requiring reoperation was obtained from the hospital records. RESULTS:
      From 1988 to 2009, 155 pulmonary autograft operations were performed. During this
      period, 41 patients required reoperation for aortic root dilatation and/or
      autograft valve insufficiency, in 8 patients combined with pulmonary allograft
      dysfunction. The freedom from autograft reoperation rate was 86% (standard error,
      3.3%) after 10 years and 52% (standard error, 6.6%) after 15 years. The median
      interval to reoperation was 15.3 years. During reoperation, 39 patients underwent
      aortic root replacement (mechanical conduit, 31; stentless root, 2; allograft, 3;
      and valve sparing, 3), and 2 patients underwent valve replacement. In 8 patients
      this was combined with pulmonary allograft replacement. The technical
      difficulties encountered included bleeding at the sternal re-entry in 5 patients.
      No 30-day mortality occurred. The postoperative complications included
      reexploration for persistent blood loss in 3 patients and cerebrovascular
      accident in 3 patients. Two patients died during the follow-up period. The
      survival rate after reoperation was 94% (standard error, 4.1%) at 5 years.
      CONCLUSIONS: An increasing number of patients requires reoperation after
      pulmonary autograft implantation. These reoperations can be done with very low
      mortality and morbidity and excellent follow-up results.

PMID- 21092800
TI  - The Bentall procedure: is it the gold standard? A series of 597 consecutive
      cases.
AB  - OBJECTIVES: We compared aortic root reconstructions using conduits with
      biological valves and mechanical valves. METHODS: Of 597 patients (1995-2008),
      307 (mean age 71 years [23-89 years]) had biological valves and 290 (mean age 51
      years [21-82 years]) had mechanical valves. The subgroup of 242 patients aged 50
      to 70 years included 133 with biological and 109 with mechanical valves. RESULTS:
      Overall hospital mortality was 3.9% with biological valves (n = 15; elective:
      3.7% [n = 10]) versus 2.8% with mechanical valves (n = 8; elective: 1.4% [n =
      3]). In patients 50 to 70 years, age greater than 65 years (relative risk: 3.3 [P
      = .0001]), clot (relative risk: 2.5 [P = .05]), coronary artery disease (relative
      risk:3.5 [P < .0001]), and degenerative etiology (relative risk: 0.4 [P = .006])
      were independent risk factors for long-term survival (after postoperative day
      30); there was no difference in long-term survival between biological and
      mechanical valves (relative risk: 0.9 [P = .74]). The linearized rate for
      valve/ascending aorta reoperation was 0.86%/pt-y (2 in 2310 pt-y) after
      mechanical valves and 2.5%/pt-y (4 in 1586 pt-y) after Bentall procedures with
      the biological valve. CONCLUSIONS: The choice of valve for aortic root
      reconstruction seems to have no influence on long-term outcome. Emergency
      operation and the presence of clot/atheroma have a significant impact on short
      term outcome. Reoperation for either ascending aorta and/or aortic valve is low.

PMID- 21092801
TI  - Long-term outcome after aortic arch replacement with a trifurcated graft.
AB  - OBJECTIVE: We describe the long-term results of aortic arch replacement using a
      trifurcated graft, including an assessment of survival, neurologic complications,
      and graft patency. METHODS: A retrospective review was conducted on data from 206
      consecutive patients (125 male; median age, 67 years; range, 20-87 years) who had
      a trifurcated graft used for aortic arch replacement between September 1999 and
      September 2009. Seventy-four patients (35.9%) had chronic dissection, 68 patients
      (33.0%) had atherosclerotic aneurysms, and 39 patients (18.9%) had degenerative
      disease. Ninety-one patients (44.2%) had undergone previous cardiac surgery.
      RESULTS: An elephant trunk was placed in 190 patients (92.2%) and completed in
      101 patients (53.1%), with an interval of less than 365 days between stages in 94
      of 101 patients. Hospital mortality was 6.8% (14/206). Adverse outcome
      (death/stroke within the first year postoperatively) occurred in 27.7% of
      patients (57/206; 50 deaths/7 strokes). Among 152 1-year survivors, the annual
      rates of transient ischemic attack and stroke were 0.85% and 1.1%, respectively.
      At 6 years, 75% of patients were still alive, compared with 92% in a matched New
      York State control population (P < .001). Follow-up computed tomography scans
      (189 studies in 176/206 patients [85.4%]) revealed 100% patency of the
      trifurcated graft limbs at a mean of 2.3 years. CONCLUSIONS: Aortic arch
      replacement using a trifurcated graft is highly durable, with excellent patency
      in the branch grafts, and is associated with a low incidence of cerebral
      embolization. However, the long-term outcome in these patients is compromised by
      extensive comorbidities.

PMID- 21092802
TI  - Classic hybrid evolving approach to distal arch aneurysms: toward the zone zero
      solution.
AB  - BACKGROUND: A combined open surgical and endovascular approach to managing
      aneurysms of the distal aortic arch (hybrid arch repair) is evolving as a viable
      treatment option. Our aim is to describe a treatment strategy in high-risk
      patients and report the technical and clinical success of the hybrid approach to
      aneurysms involving the distal aortic arch. METHODS: From July 2005 until
      December 2009, 27 consecutive patients with aneurysms of the distal aortic arch
      were treated via a hybrid arch repair. Of this group, 23 patients underwent
      aortic arch debranching and revascularization before endovascular stent
      deployment in the ascending aorta (type I). Four patients required ascending
      aortic and transverse arch replacement before stent graft deployment (type II).
      RESULTS: A stent graft was successfully deployed in 100% of patients after aortic
      arch vessel debranching via median sternotomy. The mean age of the patients was
      71 +/- 7.5 years. The average cardiopulmonary bypass time was 199 +/- 84 minutes
      with an average crossclamp time of 57 +/- 53 minutes. Deep hypothermic
      circulatory arrest was required in 4 patients (all type II). The average length
      of stay was 17.2 +/- 14 days. The complications included stroke in 3 (11%)
      patients, permanent paralysis in 2 (7%), and perioperative death in 3 (11%)
      patients. CONCLUSIONS: Early results of type I and II hybrid arch repair, in this
      cohort of patients with mutiple comorbid risk factors, are acceptable and even
      encouraging. This evolving approach to aneurysms involving the aortic arch may
      extend the indications for use of endovascular prostheses in the treatment of
      patients with complex aortic arch disease.

PMID- 21092803
TI  - Complex thoracic aortic disease: single-stage procedure with the frozen elephant
      trunk technique.
AB  - OBJECTIVE: Extensive thoracic aortic aneurysms represent a challenging pathology
      in cardiac surgery. The frozen elephant trunk procedure, combining conventional
      surgery with endovascular techniques, allows single-stage treatment for such
      pathology. Here we present our surgical technique and results with the single
      stage frozen elephant trunk procedure. METHODS: Between January 2007 and December
      2009, 67 patients were treated with the frozen elephant trunk procedure in our
      institution. Mean age was 61 +/- 11 years. Indications for surgery included
      chronic aneurysm (n = 22, 32.8%), acute type A dissection (n = 4, 6.0%), acute
      type B dissection (n = 2, 3.0%), chronic type A dissection (n = 30, 44.8%), and
      chronic type B dissection (n = 9, 13.4%). Thirty-six patients (53.7%) had
      undergone 38 previous cardiac or aortic operations. Thirty-two associated aortic
      and cardiac operations were performed. Brain protection was achieved by means of
      antegrade selective cerebral perfusion and moderate hypothermia (26 degrees C) in
      all cases. RESULTS: In-hospital mortality was 13.4%. Postoperatively, permanent
      neurologic dysfunction (coma) occurred in 5 cases (7.5%), paraplegia in 2 (3.2%),
      and paraparesis in 3 (4.9%). Follow-up was 100% complete, with mean duration of
      11.1 +/- 8.4 months. The 1- and 2-year survivals were 76.7 +/- 5.6% and 70.3 +/-
      8.0%, respectively. Ten patients (14.9%) required endovascular completion 2.3 +/-
      3.1 months after the first procedure, with 100% technical and procedural success.
      CONCLUSIONS: In contrast to the conventional elephant trunk technique, the frozen
      elephant trunk technique offers a potentially curative single-stage procedure for
      patients with extensive thoracic aortic disease, with encouraging short-term and
      midterm results.

PMID- 21092805
TI  - Acute aortic syndrome.
AB  - The term acute aortic syndrome refers to a heterogeneous group of conditions that
      cause a common set of signs and symptoms, the foremost of which is aortic pain.
      Various pathologic entities may give rise to this syndrome, but the topic has
      come to focus on penetrating aortic ulcer and intramural hematoma and their
      relation to aortic dissection. Penetrating aortic ulcer is a focal
      atherosclerotic plaque that corrodes a variable depth through the intima into the
      media. Intramural hematoma is a blood collection within the aortic wall not
      freely communicating with the aortic lumen, with restricted flow. It may
      represent a subcategory of aortic dissection that manifests different behavior by
      virtue of limited flow in the false lumen. This article reviews the current
      literature regarding acute aortic syndrome, focusing on management options.

PMID- 21092806
TI  - Treatment for malperfusion syndrome in acute type A and B aortic dissection: A
      long-term analysis.

PMID- 21092807
TI  - Root anatomy and canal configuration of the permanent mandibular first molar: a
      systematic review.
AB  - INTRODUCTION: The main goal of endodontic therapy is to prevent or heal apical
      periodontitis. However, root canal anatomy might present a clinical challenge
      directly related to the treatment outcome. The purpose of this study was to
      review published literature related to root anatomy and root canal configuration
      of the permanent mandibular first molar. METHODS: An exhaustive search was
      undertaken to identify published literature related to the root anatomy and root
      canal morphology of the permanent mandibular first molar by using key words. The
      search of the MEDLINE database included all publications from 1966-May 2010.
      Selected articles were then obtained and reviewed. Data evaluated and summarized
      in the data sheet included methodology, population, number of teeth per study
      (power), number of root canals, type of root canal configuration, and
      identification of number of apical foramina. RESULTS: Forty-one studies were
      identified including a total of 18,781 teeth. The incidence of a third root was
      13% and was strongly correlated with the ethnicity of the studied population.
      Three canals were present in 61.3%, 4 canals in 35.7%, and 5 canals in
      approximately 1%. Root canal configuration of the mesial root revealed 2 canals
      in 94.4% and 3 canals in 2.3%. The most common canal system configuration was
      Vertucci type IV (52.3%), followed by type II (35%). Root canal configuration of
      the distal root revealed type I configuration in 62.7%, followed by types II
      (14.5%) and IV (12.4%). The presence of isthmus communications averaged 54.8% on
      the mesial and 20.2% on the distal root. CONCLUSIONS: The number of roots on the
      mandibular first molar is directly related to ethnicity. Root canal morphology
      and configuration might present the clinician with a complex anatomy requiring
      more diagnostic approaches, access modifications, and clinical skills to
      successfully localize, negotiate, disinfect, and seal the root canal system.

PMID- 21092808
TI  - Radiographic parameters of quality of root canal fillings and periapical status:
      a retrospective cohort study.
AB  - INTRODUCTION: The aim of this study was to radiographically evaluate the
      relationship between the quality parameters of root canal fillings (apical
      extension, homogeneity, and taper) and periapical status. In addition, groups of
      teeth and complicating factors of endodontic treatment were assessed. METHODS:
      This retrospective cohort study assessed the quality and periapical status of
      root-filled canals in a 4- to 7-year follow-up period. Each parameter was
      dichotomized into ideal and altered conditions. A root-filled canal with an ideal
      condition for all 3 parameters was considered perfect, whereas the loss of 1 or
      more ideal conditions defined satisfactory or deficient fillings, respectively.
      The periapical statuses at baseline and follow-up were classified as normal,
      slight widening of the apical periodontal ligament, or periapical lesion.
      RESULTS: A total of 291 root-filled canals were evaluated. The prevalence of
      perfect, satisfactory, and deficient fillings was 54.6%, 37.5%, and 7.9%,
      respectively (P < .05). The periapical status at follow-up showed normal, slight
      widening of the apical periodontal ligament, or periapical lesion in 69.8%,
      19.2%, and 11% of the roots, respectively (P < .05). The multivariate logistic
      regression showed that only preoperative periapical lesions (odds ratio, 2.99;
      95% confidence interval, 1.27-7.03) and altered tapers (odds ratio, 3.73; 95%
      confidence interval, 1.51-9.24) were significantly associated with postoperative
      periapical lesions. CONCLUSIONS: Radiographic parameters of the quality of root
      filled canals showed a significant relationship with the periapical status.
      Nevertheless, an altered taper was the main factor associated with the
      maintenance or development of periapical lesions after 4- to 7-year follow-up
      period.

PMID- 21092809
TI  - The effect of three different rotary instrumentation systems on substance P and
      calcitonin gene-related peptide expression in human periodontal ligament.
AB  - INTRODUCTION: The purpose of this study was to quantify the effect of three
      different rotary root canal preparation systems on substance P and calcitonin
      gene-related peptide expression in healthy human periodontal ligament. METHODS:
      Fifty periodontal ligament samples were obtained from healthy premolars in which
      extraction was indicated for orthodontic reasons. Before extraction, 40 of these
      premolars were equally divided into four groups, and root canals were prepared
      using four different systems: the ProTaper Universal rotary system, the RaCe
      rotary system, the Mtwo rotary system, and the hand instrumentation technique.
      The remaining 10 healthy premolars that were extracted without treatment served
      as a negative control group. All periodontal ligament samples were processed, and
      SP and CGRP were measured by radioimmunoassay. RESULTS: Greater SP and CGRP
      expression were found in the ProTaper Universal group followed by the hand
      instrumentation group, the RaCe, and the Mtwo groups. The lower SP and CGRP
      values were for the negative control group. The Kruskal-Wallis test showed
      statistically significant differences between groups (p < 0.0001). Post hoc Least
      Significant Difference (LSD) tests showed statistically significant differences
      in SP and CGRP expression between the negative control group and all the other
      groups except the Mtwo group. Hand instrumentation also showed statistically
      significant differences with all the other groups, except the ProTaper Universal
      group. Differences between the three rotary systems were also statistically
      significant. CONCLUSION: SP and CGRP expression in periodontal ligament increases
      when teeth are prepared with ProTaper Universal and RaCe rotary instrumentation
      systems as well as with hand instrumentation. Mtwo maintains SP and CGRP levels.

PMID- 21092811
TI  - Prevalence, phenotype, and genotype of Enterococcus faecalis isolated from saliva
      and root canals in patients with persistent apical periodontitis.
AB  - INTRODUCTION: The aim of this study was to investigate the prevalence, phenotype,
      and genotype of Enterococcus faecalis isolated from saliva and root canals in
      patients with endodontic treatment failure. METHODS: Samples were collected from
      32 adults undergoing retreatment for periapical lesions after endodontic
      treatment performed at least 2 years previously. Isolates that were presumed to
      be E. faecalis were identified by both API20 Strep kits and 16S rRNA sequencing.
      Phenotypic tests for hemolysin and gelatinase production and antibiotic
      susceptibility were performed. Genotype analysis comprised virulence gene
      detection and pulsed field gel electrophoresis (PFGE). RESULTS: The prevalence of
      E. faecalis was 18.8% in saliva and 40.6% in root canals (P = .666, Fisher exact
      test). Of the 19 isolates of E. faecalis, 6 were from saliva and 13 were from
      root canals. In 3 patients, E. faecalis isolates from saliva were more resistant
      to gentamicin than those from root canals. The genes ace, asa, gelE, cylA, and
      efaA were detected from all isolates. PFGE after SmaI digestion showed a genetic
      correlation among all isolates of 62%-100%. CONCLUSIONS: Phenotype and genotype
      evidence of potential virulence factors was identified in E. faecalis from both
      saliva and root canals. A single patient might carry different E. faecalis
      strains in saliva and root canals.

PMID- 21092810
TI  - Association of endodontic involvement with tooth loss in the Veterans Affairs
      Dental Longitudinal Study.
AB  - INTRODUCTION: The effect of endodontic involvement on tooth loss has not been
      quantified, so the present study aimed to assess this relationship after
      controlling for other relevant risk factors for tooth loss. METHODS: We analyzed
      data from 791 participants (18,798 teeth) in the Veterans Affairs Dental
      Longitudinal Study. Potential tooth-level and person-level covariates were fitted
      into marginal proportional hazards models, including both apical radiolucencies
      (AR) and root canal therapy (RCT) status as time-dependent variables. Survival
      curves were plotted for teeth according to their AR and RCT status. RESULTS: Both
      current AR and RCT status were associated with increased risk of tooth loss (P <
      .01), after controlling for baseline levels of periodontal disease, caries, tooth
      type, number of proximal contacts, number of teeth, age, education, and smoking
      history. Root canal filled (RCF) teeth seemed to have better survival than non
      RCF teeth among teeth with AR but worse survival than non-RCF teeth among teeth
      without AR. CONCLUSIONS: Endodontic involvement was associated with tooth loss,
      controlling for other potential risk factors. Additional prospective studies are
      needed to provide better evidence as to the impact of endodontic involvement on
      tooth loss.

PMID- 21092812
TI  - Tertiary dentin formation after direct pulp capping with odontogenic ameloblast
      associated protein in rat teeth.
AB  - INTRODUCTION: Odontogenic ameloblast-associated protein (ODAM) has been shown to
      be specifically expressed in ameloblasts and odontoblasts and has been suggested
      to play a role in the mineralization of the enamel, possibly through the
      regulation of matrix metalloproteinase 20. However, its function in dentin is not
      clear. The purpose of this study was to evaluate the effect of ODAM on tertiary
      dentin formation. METHODS: MDPC-23 odontoblastic cells were cultured, and the
      effect of recombinant ODAM (rODAM) on mineralized nodule formation was evaluated.
      Pinpoint pulp exposures were made in rat teeth and then capped with rODAM mixed
      with a carrier (rODAM group), carrier only (Carrier group), or white mineral
      trioxide aggregate (WMTA group). After 1, 2, and 4 weeks, odontoblasts and
      tertiary dentin were investigated histologically and immunohistochemically.
      RESULTS: Nodule formation in MDPC-23 cells was enhanced by rODAM treatment.
      Odontoblasts were polarized and showed a palisade arrangement in the remaining
      pulp from the rODAM group, but not the Carrier or WMTA groups. In the WMTA group,
      extensive tertiary dentin along the entire pulp-dentin border obliterated the
      pulp chamber. In contrast, in the rODAM group, limited reaction of odontoblasts
      resulted in normal pulp tissue appearance without excessive tertiary dentin
      formation and obliteration of the pulp cavity. In the Carrier and WMTA groups,
      bone sialoprotein was immunostained in most of the tertiary dentin, whereas in
      the rODAM group, dentin sialoprotein expression was immunostained primarily in
      newly formed reactionary dentin. CONCLUSIONS: These results suggest that rODAM
      accelerates reactionary dentin formation close to the pulp exposure area, thereby
      preserving normal odontoblasts in the remaining pulp.

PMID- 21092813
TI  - Dental pulp stem cell migration.
AB  - INTRODUCTION: The purpose of this in vitro study was to investigate the migration
      of dental pulp stem cells (DPSCs) in response to chemotactants and extracellular
      matrix proteins (EMPs). This DPSC signaling information is needed to help
      understand tooth regeneration after injury and to develop some future
      regenerative endodontic therapies. METHODS: DPSCs were released by trypsinization
      and plated on transwell filters. The chemotactants were recombinant sphingosine-1
      phosphate (S1P), fibroblast growth factor (FGF), epidermal growth factor (EGF),
      or transforming growth factor beta-1 (TGF-beta1), and the EMPs were collagen-1,
      collagen-IV, laminin, and fibronectin. Data were analyzed by using analysis of
      variance (ANOVA) statistical tests for cell migration. RESULTS: S1P induced more
      vigorous DPSC migration in comparison with the other TGF- beta1, FGF, or EFG
      chemotactants (ANOVA, P < .05). Laminin induced more vigorous DPSC migration in
      comparison with the other EMPs (ANOVA, P < .05). CONCLUSIONS: The EMPs,
      particularly laminin, and chemotactants, particularly S1P and TGF-beta1, were
      found to be important promoters of DPSC migration. The interplay between the
      EMPs, blood lipid, serum, and chemotactants suggests that the migration of DPSC
      is highly regulated. Specific chemotactants and EMPs might mediate the process of
      pulp-dentin regeneration after tooth injury, and they could be used as part of
      regenerative endodontic therapy.

PMID- 21092815
TI  - Expression of erythropoietin and erythropoietin receptor in human dental pulp.
AB  - INTRODUCTION: In addition to the involvement in erythropoiesis, erythropoietin
      (EPO) and its receptor (EPO-R) have been shown to be expressed in various
      nonhematopoietic organs and tissues with diverse biological effects. The purpose
      of this study was to evaluate the expression patterns of EPO and EPO-R in healthy
      and inflamed human dental pulp tissues. To gain insight into the possible
      mechanisms involved in the regulation of EPO and EPO-R expression, we further
      investigated the hypothesis that their expression in cultured human dental pulp
      cells (DPCs) may be regulated upon hypoxia, an important factor involved in
      dental pulp inflammation. METHODS: Samples of healthy and inflamed dental pulp
      tissues were obtained from patients undergoing surgical or orthodontic treatment.
      The protein localization and messenger RNA levels of EPO and EPO-R in the pulp
      tissues were detected by immunohistochemistry and quantitative real-time
      polymerase chain reaction (PCR), whereas the EPO and EPO-R expressions in DPCs in
      vitro were evaluated by Western blotting and quantitative real-time PCR. RESULTS:
      EPO and EPO-R proteins were detected in inflamed dental pulp, whereas no obvious
      EPO expression was detected in healthy dental pulp. The EPO messenger RNA level
      was significantly up-regulated in inflamed pulps compared with healthy pulps.
      Moreover, the messenger RNA and protein levels of EPO and EPO-R were up-regulated
      in DPCs under hypoxia in vitro. CONCLUSIONS: The up-regulation of EPO might be
      involved in dental pulp inflammation, which is probably attributed to hypoxia.
      Further studies are needed to investigate the potential role of EPO and EPO-R in
      dentin-pulp repair and regeneration.

PMID- 21092814
TI  - Attenuation of AH26-induced apoptosis by inhibition of SAPK/JNK pathway in MC-3T3
      E1 cells.
AB  - INTRODUCTION: The cytotoxicity of AH26, a resin-based sealer, induces apoptosis
      in osteoblast cells. However, the apoptosis pathway is not completely understood.
      This study examined the apoptosis pathway and its regulation of AH26 through
      mitogen-activated protein kinase (MAPKs), which may play a role in reducing the
      cytotoxicity of AH26. METHODS: Using mouse osteoblasts cells (MC-3T3-E1),
      specimens of AH26 were eluted with the culture medium for 1, 3, 5, and 7 days.
      The cytotoxicity was tested using an 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The induction of apoptosis was detected by
      Hoechst33258 staining and poly (ADP-ribose) polymerase (PARP) activation. The
      AH26-involved signal pathway was analyzed by immunoblotting with a specific
      antibody. RESULTS: AH26 exhibited cytotoxicity toward MC-3T3-E1 cells, which
      resulted in mitochondria-mediated apoptosis, as confirmed by Bax expression and
      the displacement of cytochrome c from mitochondria to cytosol. As evidence of
      MAPKs activation, the cells treated with AH26 expressed stress-activated
      protein/c-jun N-terminal kinase (SAPK/JNK) and extracellular signal-regulated
      protein kinase (ERK1/2). SAPK/JNK activation appears to regulate apoptosis,
      whereas ERK activation protects cell survival. CONCLUSIONS: From these results,
      the toxicity of AH26 can be decreased by controlling the apoptosis signals. This
      approach might have potential applications for reducing the long-term stress of
      periapical tissue that improves endodontic treatment.

PMID- 21092816
TI  - Effects of iRoot SP on mineralization-related genes expression in MG63 cells.
AB  - INTRODUCTION: The purpose of this study was to assess the effects of iRoot SP
      root canal sealer (Innovative BioCreamix Inc, Vancouver, Canada) on the
      expression of mineralization-related genes in human MG63 osteoblast-like cells.
      METHODS: Specimens (5 mm in diameter and 2 mm in height) of iRoot SP and AH Plus
      (Dentsply DeTrey, Konstanz, Germany) were extracted from a 5-mL culture medium.
      The MG63 cells were exposed to various dilutions (1/1, 1/2, and 1/4) of the
      extracts. The 3,(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT
      assay was used for assessing the dental materials' nonspecific cytotoxicity. The
      expression of mineralization-related genes, including collagen type I (COL I),
      osteocalcin (OCN), bone sialoprotein (BSP) and osteopontin (OPN), was detected on
      days 1, 3, and 6 by a real-time polymerase chain reaction. An enzyme-linked
      immunosorbent assay experiment was used for evaluating COL I and BSP protein
      changes. The data were analyzed with one-way analysis of variance and Tukey
      tests. RESULTS: In the MTT assay, the undiluted extracts of iRoot SP were
      noncytotoxic, whereas the undiluted extracts of AH Plus were rated as slightly
      cytotoxic. iRoot SP up-regulated COL I, OCN, and BSP messenger RNA expression
      after 3 and 6 days. In the enzyme-linked immunosorbent assay experiment, iRoot SP
      increased COL I and BSP protein levels compared with AH Plus and the control
      group on day 6. CONCLUSIONS: In the presence of iRoot SP, MG63 cells can produce
      more mineralized matrix gene and protein expression. Based on these results,
      iRoot SP can be considered as a favorable material for cell-material interaction.

PMID- 21092817
TI  - Effectiveness of different irrigant agitation techniques on debris and smear
      layer removal in curved root canals: a scanning electron microscopy study.
AB  - INTRODUCTION: The aim of this study was to evaluate the cleaning efficacy of
      different irrigant agitation techniques on debris and smear layer removal in
      curved root canals. METHODS: Mesiobuccal root canals of 108 mandibular molars
      were shaped with nickel-titanium instruments, and a final rinse of NaOCl and
      ethylenediaminetetraacetic acid was performed. Specimens were assigned to 4
      groups (n = 20) and submitted to the following irrigation agitation techniques:
      no agitation (control), ultrasonic, EndoActivator, and CanalBrush. Root canals
      were split longitudinally and subjected to scanning electron microscopy. The
      presence of debris and smear layer at coronal and apical levels was evaluated by
      using a 5-grade scoring system with 200* and 1000* magnification, respectively.
      RESULTS: Concerning debris removal, no significant differences among groups were
      detected. In the coronal region, agitation of the irrigants resulted in
      significantly more smear layer removal than the control. EndoActivator was
      significantly more effective than ultrasonic agitation and CanalBrush.
      CONCLUSIONS: In curved root canals, activation of NaOCl and
      ethylenediaminetetraacetic acid did not enhance debris removal but resulted in
      significantly more effective smear layer removal at coronal levels.

PMID- 21092818
TI  - Analysis of arsenic in gray and white mineral trioxide aggregates by using atomic
      absorption spectrometry.
AB  - INTRODUCTION: The aim of the present study was to investigate whether the
      concentration of arsenic (As) released from gray or white mineral trioxide
      aggregates (MTAs) met the requirement of the International Standards Organization
      (ISO) for dental cements. METHODS: Sample preparations were carried out according
      to the ISO methods. After centrifugation of dissolved samples, As (III)
      concentration in the final supernatant was analyzed by a high-performance atomic
      absorption spectrophotometer. RESULTS: As (III) concentration from both MTAs was
      much less than the required value (2 ppm) for dental cements regulated by the
      ISO. An experiment simulating pulp capping by using MTA revealed that As
      concentration was also below the standard value of the ISO. The As concentration
      in white MTA was lower than the value (10 ppb) recommended for tap water and
      environmental standards. CONCLUSIONS: The present in vitro studies demonstrated
      that there is no threat to patient health in using commercially available brands
      of MTA for endodontic practices.

PMID- 21092819
TI  - Lifespan of one nickel-titanium rotary file with reciprocating motion in curved
      root canals.
AB  - INTRODUCTION: The purpose of this study was to examine the lifespan of one nickel
      titanium (NiTi) rotary file when used in reciprocating motion and to compare the
      time required for its preparation of a curved root canal using both reciprocating
      and continuous motion. METHODS: One hundred twenty curved canals from 60
      extracted maxillary and mandibular molars were selected for measuring the mean
      number of uses. Each canal was prepared with reciprocating motion until the
      ProTaper F2 single file (Dentsply Maillefer, Ballaigues, Switzerland) reached the
      working length. One file was used until it was fractured. Another 60 canals were
      divided into two groups. 30 canals in the continuous rotation motion (CM) group
      were prepared using continuous rotation following the sequence of ProTaper files,
      whereas the canals in the reciprocating motion (RM) group (n = 30) were prepared
      with reciprocating motion with the sole use of the ProTaper F2. The total root
      canal preparation time was measured until the F2 file finally reached the working
      length in both groups. RESULTS: A total of 11 files were used in the preparation
      of 120 curved root canals. The average lifespan of one F2 file was 10.60 +/- 4.35
      canals with the longest lifespan of 21 canals. The total time for canal
      preparation was 46.42 +/- 18.12 seconds and 21.15 +/- 6.70 seconds in the CM and
      RM groups, respectively. There was a statistically significant difference between
      the groups (p < 0.01). CONCLUSION: Within the limitation of this study, one F2
      file can be safely used to the working length of curved canals at least six times
      under reciprocating motion. Reciprocating preparation with only one F2 file was
      much faster than root canal instrumentation with continuous rotation.

PMID- 21092820
TI  - Effects of root canal irrigants on the push-out strength and hydration behavior
      of accelerated mineral trioxide aggregate in its early setting phase.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effects of endodontic
      irrigants on the push-out strength and hydration behavior of accelerated mineral
      trioxide aggregate (MTA) in its early setting phase. METHODS: In an in vitro
      perforation model, MTA with or without 10% CaCl(2) was condensed and allowed to
      initial set for 10 minutes. The samples were divided into four groups (n = 10) to
      be immersed into either 3.5% sodium hypochlorite (NaOCl) or 2% chlorhexidine
      gluconate (CHX) for 30 minutes and then allowed to set for 48 hours. In the
      control group, a wet cotton pellet was placed over MTA. The maximum force applied
      to the set MTA mixture before dislodgement was recorded. Irrigant-treated
      surfaces were examined using a scanning electron microscope (SEM). Chemical
      elements of these surfaces were also analyzed by energy dispersive x-ray
      spectroscope (EDS). RESULTS: The push-out strength of group A1 (NaOCl-treated
      accelerated MTA) was the highest of all groups. When compared with nonaccelerated
      MTA, CaCl(2)-accelerated MTA showed significantly higher push-out strength (p <
      0.05). NaOCl-treated groups showed significantly higher push-out strength than
      CHX-treated groups (p < 0.05). Scanning electron microscopic examination and EDS
      analysis showed that the formation of calcium hydroxide crystals on accelerated
      MTA exposed to NaOCl was increased compared with those of the control group.
      CONCLUSION: These findings imply that the use of accelerated MTA under the NaOCl
      irrigation was effective in perforation repair without altering its hydration
      behavior even in the early setting phase.

PMID- 21092821
TI  - Dislocation resistance of iRoot SP, a calcium silicate-based sealer, from
      radicular dentine.
AB  - INTRODUCTION: The aim of this study was to evaluate the push-out bond strength of
      iRoot SP (Innovative Bioceramix, Vancouver, Canada) and compare it with that of
      other widely used root canal sealers. METHODS: Sixty extracted human maxillary
      canines were sectioned transversally below the cement-enamel junction to obtain
      120 4-mm-thick dentin disks that were randomly divided into four groups (n = 30)
      for treatment with one of four different root-canal sealers (iRoot SP, AH Plus
      [Dentsply DeTrey GmbH, Konstanz, Germany], Sealapex [SybronEndo Corporation,
      Orange, CA], EndoREZ [Ultradent Inc, South Jordan, UT]). Standardized cavities
      were prepared to simulate root canals, cavities were filled with sealer material,
      and push-out bond-strength testing was performed using a universal testing
      machine. Failure modes were assessed quantitatively under a stereomicroscope and
      morphologically under a scanning electron microscope. Statistical analysis was
      performed using one-way analysis of variance and the post hoc Tukey test, with
      the significance level set at 0.05. RESULTS: Bond strengths of iRoot SP and AH
      Plus were significantly higher than those of Sealapex and EndoREZ. There was no
      significant difference between the bond strength of iRoot SP and AH Plus (p =
      0.274). CONCLUSIONS: iRoot SP and AH Plus performed similarly and better than
      EndoREZ and Sealapex in terms of bond strength.

PMID- 21092822
TI  - Accuracy of three electronic apex locators compared with digital radiography: an
      ex vivo study.
AB  - INTRODUCTION: This study compared (1) the accuracy of three different electronic
      apex locators (EALs) in detecting the apical foramen ex vivo under clinical
      conditions; (2) the accuracy of digital radiography and EALs in determining the
      working length (WL) with visible control under a microscope; and (3) the
      precision of #10, #15, and #20 K-files in electronic measurements. METHODS: The
      length of 101 extracted human teeth was measured with three different EALs (Endex
      [Osada Electric Co, Tokyo, Japan], ProPex II [Dentsply-Maillefer, Ballaigues,
      Switzerland], and Root ZX [J. Morita Co, Tustin, CA]), with radio videography
      (RVG) and compared with the actual length. An endodontic training kit (Pro-Train;
      Simit Dental, Mantova, Italy) was used during the experimental procedures.
      RESULTS: Statistical analysis showed that Endex and ProPex II were more accurate
      than Root ZX in determining the WL. The paired sample t test showed no
      statistically significant difference between the accuracy of the two radiographic
      planes examined. The t test showed no significant difference between the three
      different K-file sizes measurements. CONCLUSIONS: Endex and ProPex II were more
      accurate than Root ZX in determining the actual WL. Instrument sizes of hand
      files did not affect the accuracy of EALs. EALs showed to be more accurate in
      determining the WL than RVG.

PMID- 21092823
TI  - Effects of concentrations and exposure times of sodium hypochlorite on dentin
      deproteination: attenuated total reflection Fourier transform infrared
      spectroscopy study.
AB  - INTRODUCTION: The purpose of this study was to quantitatively analyze the effects
      of different concentrations and exposure times of sodium hypochlorite (NaOCl) on
      dentin deproteination and to determine the suitable concentrations and exposure
      times to minimize the effects of deproteination on dentin. METHODS: Intact human
      dentin slabs were treated with 0.5%, 1%, or 2.25% NaOCl for 1, 5, or 10 minutes.
      A 0.9% NaCl solution served as the control. To investigate the effect of NaOCl on
      the surface chemical changes to human dentin, the attenuated total reflection
      Fourier transform infrared (ATR-FTIR) spectroscopy technique was used to analyze
      the amide:phosphate ratio and carbonate:phosphate ratio. RESULTS: The
      amide:phosphate ratio decreased significantly after NaOCl treatment as compared
      with the control group (p < 0.05). In the 0.5% NaOCl treatment group, the
      amide:phosphate ratio was significantly higher than that in the 1% and the 2.25%
      NaOCl treatment groups (p < 0.05). The different exposure times (1, 5, or 10
      minutes) of NaOCl within the same concentration did not influence the
      amide:phosphate ratio (p > 0.05). NaOCl treatment did not affect the
      carbonate:phosphate ratio (p > 0.05). CONCLUSIONS: NaOCl, 0.5%, is recommended as
      the predominant concentration for routine use during root canal therapy to
      minimize any NaOCl-induced dentin deproteination. It is suggested that a
      prolonged exposure to low concentrations of NaOCl is less damaging to dentin in
      attempting to achieve antisepsis during instrumentation of root canal therapy.

PMID- 21092824
TI  - Invasive cervical resorption Class III in a maxillary central incisor: diagnosis
      and follow-up by means of cone-beam computed tomography.
AB  - INTRODUCTION: Invasive cervical resorption (ICR) is a type of external resorption
      that begins below the epithelial attachment. The etiology of ICR is mainly caused
      by trauma or orthodontic treatment. In many cases, cone-beam computed tomography
      (CBCT) is a very useful tool to achieve proper diagnosis. METHODS: This case
      presented with invasive cervical resorption class III (Heithersay) caused by
      trauma on tooth #9. CBCT was performed allowing observation of the extent of the
      lesion in the three spatial planes. RESULTS: Treatment was combined: surgical
      treatment to expose the resorptive defect and nonsurgical root canal therapy to
      remove the necrotic pulp and disinfect the root canal system; finally, the
      resorptive defect was filled up with resin ionomer (Geristore; Den-Mat
      Corporation, Santa Maria, CA). CONCLUSIONS: Follow up x-ray films showed healing
      of the periradicular tissues, and then a control CBCT was performed to assess the
      reliability of the conventional x-ray film; a small periapical lesion was
      observed in two of the CBCT sections.

PMID- 21092829
TI  - The Know & Go! program improves knowledge for patients with coronary heart
      disease in pilot testing.
AB  - OBJECTIVE: To determine if patients hospitalized for angioplasty could learn
      about symptoms, risk factors, and care-seeking behaviors before and after
      discharge and to assess patient acceptability of the intervention. METHODS:
      Thirty-two women and 32 men were randomly assigned to groups and completed an
      intervention pretest. The experimental group viewed the Know & Go! slide
      presentation at baseline and 2 and 4 months after discharge. A satisfaction
      survey was mailed to patients in the experimental group. RESULTS: There were no
      significant differences between groups in clinical or sociodemographic
      characteristics. The experimental group scored significantly higher on an
      intervention posttest at study completion (F = 15.21; P < .001). Patients were
      highly satisfied with the program and computer technology (range 0-12, M = 9.57
      +/- 1.83). CONCLUSION: The Know & Go! intervention was safe, effective, and
      acceptable to patients in pilot testing. Results support refinement and further
      testing of the intervention for patients diagnosed with coronary heart disease.

PMID- 21092830
TI  - Technology-enhanced practice for patients with chronic cardiac disease: home
      implementation and evaluation.
AB  - OBJECTIVE: This 3-year field experiment engaged 60 nurses and 282 patients in the
      design and evaluation of an innovative home-care nursing model, referred to as
      technology-enhanced practice (TEP). METHODS: Nurses using TEP augmented the usual
      care with a web-based resource (HeartCareII) that provided patients with self
      management information, self-monitoring tools, and messaging services. RESULTS:
      Patients exposed to TEP demonstrated better quality of life and self-management
      of chronic heart disease during the first 4 weeks, and were no more likely than
      patients in usual care to make unplanned visits to a clinician or hospital. Both
      groups demonstrated the same long-term symptom management and achievements in
      health status. CONCLUSION: This project provides new evidence that the purposeful
      creation of patient-tailored web resources within a hospital portal is possible;
      that nurses have difficulty with modifying their practice routines, even with a
      highly-tailored web resource; and that the benefits of this intervention are more
      discernable in the early postdischarge stages of care.

PMID- 21092831
TI  - Classification of the thyroid nodules based on characteristic sonographic
      textural feature and correlated histopathology using hierarchical support vector
      machines.
AB  - In this study, the ultrasound images of thyroid nodules were classified to
      facilitate clinical diagnosis and management. The hierarchical support vector
      machines (SVM) classification system was used to select the characteristic
      sonographic textural feature that represents the major histopathologic components
      of the thyroid nodules. Two ultrasound systems (LA39 and i12L mentioned in the
      Materials and Methods section) were used for comparison. Seventy-six thyroid
      nodular lesions and 157 regions-of-interest thyroid ultrasound image from each
      system were recruited in the study. The parameters affecting image acquisition
      were kept in the same condition for all lesions. Commonly used texture analysis
      methods were applied to characterize thyroid ultrasound images. Image features
      were classified according to the corresponding pathologic findings. To estimate
      their relevance and performance to classification, SVMs were used as a feature
      selector and a classifier. The thyroid nodules are first categorized as two main
      types, i.e., follicle base and fibrosis base nodule, by sum average. The follicle
      base nodules can be further and completely classified into follicles with few
      cells, follicles with follicular cells and follicles with papillary cancer cells
      by run length nonuniformity (RLNU). The fibrosis base nodules are further
      classified by sum square into fibrosis with few cells and fibrosis with dominant
      cells. The fibrosis base neoplasm with dominant cells can be separated into
      fibrosis with follicular cells and fibrosis with papillary cancer cells by
      entropy. The hierarchical SVM classification system achieves a diagnostic
      accuracy between 96.34% and 100%. Besides, the best sonographic textural feature
      can be selected by the system for the differentiation between the follicle and
      fibrosis base thyroid nodules or the cell types mixed in them. In follicle base
      thyroid nodules, papillary cancers show higher sonographic textural RLNU but less
      than follicular cells. In fibrosis base thyroid nodules, papillary cancers show
      increased sonographic textural variance and entropy.

PMID- 21092832
TI  - Nonlinear contrast imaging with an array-based micro-ultrasound system.
AB  - The main goal of this study was to determine the optimal strategy for a real-time
      nonlinear contrast mode for small-animal imaging at high frequencies, on a new
      array-based micro-ultrasound system. Previously reported contrast imaging at
      frequencies above 15 MHz has primarily relied on subtraction schemes involving B
      mode image data. These approaches provide insufficient contrast to tissue ratios
      under many imaging conditions. In this work, pulse inversion, amplitude
      modulation and combinations of these were systematically investigated for the
      detection of nonlinear fundamental and subharmonic signal components to maximize
      contrast-to-tissue ratio (CTR) in the 18-24 MHz range. From in vitro and in vivo
      measurements, nonlinear fundamental detection with amplitude modulation provided
      optimal results, allowing an improvement in CTR of 13 dB compared with
      fundamental imaging. Based on this detection scheme, in vivo parametric images of
      murine kidneys were generated using sequences of nonlinear contrast images after
      intravenous bolus injections of microbubble suspensions. Initial parametric
      images of peak enhancement (PE), wash-in rate (WiR) and rise time (RT) are
      presented. The parametric images are indicative of blood perfusion kinetics,
      which, in the context of preclinical imaging with small animals, are anticipated
      to provide valuable insights into the progression of human disease models, where
      blood perfusion plays a critical role in either the diagnosis or treatment of the
      disease.

PMID- 21092833
TI  - Dose-response effect of charged carbon beam on normal rat retina assessed by
      electroretinography.
AB  - PURPOSE: To compare the effects of carbon beam irradiation with those of proton
      beam irradiation on the physiology of the retina of rats. METHODS AND MATERIALS:
      Eight-week-old Wister rats were used. The right eyes were irradiated with carbon
      beam (1, 2, 4, 8, and 16 Gy) or proton beam (4, 8, 16, and 24 Gy) with the rats
      under general anesthesia. Electroretinograms were recorded 1, 3, 6, and 12 months
      after the irradiation, and the amplitudes of the a and b waves were compared with
      those of control rats. RESULTS: The amplitude of b waves was reduced more than
      that of a waves at lower irradiation doses with both types of irradiation. With
      carbon ion irradiation, the amplitudes of the b wave were significantly reduced
      after radiation doses of 8 and 16 Gy at 6 months and by radiation doses of 4, 8,
      and 16 Gy at 12 months. With proton beam irradiation, the b-wave amplitudes were
      significantly reduced after 16 and 24 Gy at 6 months and with doses of 8 Gy or
      greater at 12 months. For the maximum b-wave amplitude, a significant difference
      was observed in rats irradiated with carbon beams of 4 Gy or more and with proton
      beams of 8 Gy or more at 12 months after irradiation. CONCLUSIONS: These results
      indicate that carbon beam irradiation is about two times more damaging than
      proton beam irradiation on the rat retina at the same dose.

PMID- 21092834
TI  - Impact of prolonged fraction delivery times simulating IMRT on cultured
      nasopharyngeal carcinoma cell killing.
AB  - PURPOSE: To determine the impact of prolonged fraction delivery times (FDTs)
      simulating intensity-modulated radiotherapy (IMRT) on cultured nasopharyngeal
      carcinoma (NPC) cell killing. METHODS AND MATERIAL: Cultured NPC cell lines CNE1
      and CNE2 were used in this study. The biological effectiveness of fractionated
      irradiation protocols simulating conventional external beam radiotherapy and IMRT
      (FDT of 15, 36, and 50 minutes) was estimated with standard colony assay, and the
      differences in cell surviving fractions after irradiation with different
      protocols were tested by use of the paired t test. The impact degree of prolonged
      FDTs (from 8 to 50 minutes) on cell killing was also assessed by the dose
      modifying factors, which were estimated by comparing the effectiveness of
      intermittently delivered 2 Gy with that of continuously delivered 1.5 to 2 Gy.
      RESULTS: The cell surviving fractions of both CNE1 and CNE2 after fractionated
      irradiation simulating IMRT were higher than those simulating conventional
      external beam radiotherapy (p < 0.05). The dose-modifying factors for a fraction
      dose of 2 Gy increased from 1.05 to 1.18 for CNE1 and from 1.05 to 1.11 for CNE2
      with the FDT being prolonged from 15 to 50 minutes. CONCLUSIONS: This study
      showed that the prolonged FDTs simulating IMRT significantly decreased the cell
      killing in both CNE1 and CNE2 cell lines, and these negative effects increased
      with the FDT being prolonged from 15 to 50 minutes. These effects, if confirmed
      by in vivo and clinical studies, need to be considered in designing IMRT
      treatments for NPC.

PMID- 21092835
TI  - Randomized comparison of whole brain radiotherapy, 20 Gy in four daily fractions
      versus 40 Gy in 20 twice-daily fractions, for brain metastases. In regard to
      Graham et al. (Int J Radiat Oncol Biol Phys 2010;77(3):648-54.).

PMID- 21092836
TI  - Defining radiotherapy target volumes using 18F-fluoro-deoxy-glucose positron
      emission tomography/computed tomography: still a Pandora's box?: in regard to
      Devic et al. (Int J Radiat Oncol Biol Phys 2010).

PMID- 21092837
TI  - Selective nodal irradiation on basis of (18)FDG-PET scans in limited-disease
      small-cell lung cancer: a prospective study. In regard to van Loon et al. (Int J
      Radiat Oncol Biol Phys 2010;77:329-336).

PMID- 21092840
TI  - Response to "Integrated prostate cancer centers and overutilization of IMRT: a
      close look at fee-for-service medicine in radiation oncology." (Int J Radiat
      Oncol Biol Phys 2010;78:1285-1288).

PMID- 21092842
TI  - Preface: Rheumatic manifestations of endocrine disease.

PMID- 21092843
TI  - Musculoskeletal manifestations of thyroid disease.
AB  - The relationship between thyroid disorders and rheumatic diseases is
      significant.Thyroid diseases not only emulate rheumatic disease with findings
      such as myopathy or arthropathy but also frequently manifest with primary
      rheumatologic complaints that the practitioner should be wary of, such as calcium
      pyrophosphate deposition disease. There is increasing recognition of the
      prevalence of autoimmune thyroid diseases in patients with connective tissue
      disorder, highlighting a common mechanism for the disease pathogenesis, which
      requires further inquiry.

PMID- 21092844
TI  - Parathyroid disease.
AB  - Patients with parathyroid disease can have important musculoskeletal
      problems.Hypoparathyroidism can cause subcutaneous calcifications, tetany, muscle
      cramps,and paresthesias, but also myopathies and an ankylosing spondylitis-like
      back disease. Hypoparathyroidism can occur in SLE caused by antiparathyroid
      antibodies.Patients with hyperparathyroidism can develop bone disease with cysts,
      erosions,and deformities. They can also develop pseudogout, gout, myopathies, and
      tendon ruptures.

PMID- 21092845
TI  - Osteoporosis and osteomalacia.
AB  - As the population ages, the amount of metabolic bone disease and number of
      fractures will increase. It is imperative that health care providers screen and
      treat patients at risk of metabolic bone disease. There is much research ongoing
      in this field and the number of treatment options will greatly expand. Focusing
      on ways to maximize the development of the fetal skeleton to improve peak bone
      mass, such as improving maternal vitamin D levels during pregnancy, may best
      address the treatment of osteoporosis and osteomalacia for the entire population.

PMID- 21092846
TI  - Rheumatic manifestations of diabetes mellitus.
AB  - DM is associated with various musculoskeletal manifestations. The strength of
      this relationship varies among the various musculoskeletal disorders; the
      associations are based mostly on epidemiologic data. For most of these
      conditions, definitive pathophysiologic correlates are lacking.Hand and shoulder
      disorders occur more frequently than other musculoskeletal manifestations of DM.
      Recognition of the association between DM and shoulder adhesive capsulitis, DD,
      and stenosing flexor tenosynovitis facilitates their correct diagnosis in the
      setting of DM and prompt initiation of appropriate treatment, which may include
      optimizing glycemic control. Conversely, awareness and identification of the
      characteristic musculoskeletal manifestations of DM may facilitate earlier
      diagnosis of DM and initiation of glucose-lowering therapy to retard the
      development of diabetic complications.Much less has been published about the
      musculoskeletal complications of DM than about its micro- and macrovascular
      complications. Prospective case-control cohort studies are needed to establish
      the true prevalence of musculoskeletal complications of DM and the metabolic
      syndrome, especially in this era of tighter glycemic control.The potential
      relationship between DM and the development of OA needs to be clarified in large,
      prospective, case-control cohort studies. The effect on musculoskeletal
      manifestations of various therapeutic regimens to manage DM should be studied
      prospectively. Treatment regimens for some musculoskeletal conditions associated
      with DM, such as DISH, should be studied in larger prospective,
      randomized,controlled clinical trials.At the molecular level, further studies are
      warranted to clarify the potential contribution of AGEs and adipokines to the
      development of OA and diabetic musculoskeletal syndromes, such as shoulder
      adhesive capsulitis, DD, stenosing flexor tenosynovitis, and LJM. Identification
      of such molecular targets for therapy would promote the development of additional
      treatments for these and other rheumatic diseases.

PMID- 21092847
TI  - Adrenal disorders in rheumatology.
AB  - Understanding adrenal disorders, whether endogenous or related to glucocorticoid
      use is important to the day-to-day care of patients with rheumatologic disease.

PMID- 21092848
TI  - Arthropathy in acromegaly.
AB  - Articular involvement in acromegaly is one of the most frequent clinical
      complications and may be present as the earliest symptom in a significant
      proportion of patients. The involvement of other organs may be of clinical
      importance and contribute to increased morbidity and mortality of patients
      suffered from acromegaly. Early diagnosis and proper treatment of the diseases
      can prevent the development of irreversible complications of the disease and
      improve the quality of life in patients suffering from the disease.

PMID- 21092849
TI  - Hypothalamic-pituitary-adrenal axis in rheumatoid arthritis.
AB  - The controlled data accumulated so far support only subtle alterations in HPA
      axis function in RA, mainly at the adrenal level, and particularly in a subset of
      premenopausal-onset women. Such interpretation is supported by consistent
      findings of lower levels of adrenal androgens, particularly DHEAS, in
      premenopausal-onset RA patients. Consequences of the subtle HPA alterations in RA
      for the disease development remain unclear. From a broader perspective, the
      unresponsiveness of the HPA axis to chronic inflammation in RA simply can be seen
      as an ongoing adaptation to the disease state with higher priority to proper
      regulation of core body functions over the immune homeostasis.

PMID- 21092850
TI  - Rheumatologic manifestations of pregnancy.
AB  - Pregnancy, whether normal or complicated, induces change in nearly every system
      of the body. Because most rheumatologic disorders are multisystemic and often
      affect young women, it may be difficult to differentiate pregnancy-related change
      from new onset or exacerbation of rheumatic disease. Familiarity with common
      manifestations of pregnancy is important in evaluating young women of
      childbearing age,whether or not they have known rheumatologic disease.
      Presentation of new connective tissue disease during pregnancy is often
      associated with poorer prognosis, so it is especially important to distinguish
      between pregnancy-induced change and true autoimmune inflammation requiring
      prompt and aggressive therapy.

PMID- 21092851
TI  - Sorting out frontotemporal dementia?
AB  - Mutations within the granulin (GRN) gene that encodes progranulin (PGRN) cause
      the neurodegenerative disease frontotemporal lobar degeneration with ubiquitin
      inclusions (FTLD-U). The receptor for PGRN in the CNS has not been previously
      identified. In this issue of Neuron, Hu and colleagues identify Sortilin (SORT1)
      as a key neuronal receptor for PGRN that facilitates its endocytosis and
      regulates PGRN levels in vitro and in vivo.

PMID- 21092852
TI  - The cytomatrix protein bassoon contributes to fast transmission at conventional
      and ribbon synapses.
AB  - The presynaptic active zone contains a complex web of proteins involved in
      synaptic transmission. In this issue of Neuron, two articles show evidence that
      one of these proteins, Bassoon, coordinates multiple functions in a conventional
      and ribbon-type synapse.

PMID- 21092853
TI  - A recipe for bidirectional motor learning: using inhibition to cook plasticity in
      the vestibular nuclei.
AB  - In this issue of Neuron, McElvain et al. demonstrate for the first time
      plasticity at the synapse between vestibular nerve afferents and their
      postsynaptic targets in the medial vestibular nuclei. This new type of
      plasticity, which is gated by inhibition, is well suited to drive motor learning
      during adaptation of the vestibulo-ocular reflex.

PMID- 21092854
TI  - Molecular motors in neurons: transport mechanisms and roles in brain function,
      development, and disease.
AB  - The kinesin, dynein, and myosin superfamily molecular motors have fundamental
      roles in neuronal function, plasticity, morphogenesis, and survival by
      transporting cargos such as synaptic vesicle precursors, neurotransmitter and
      neurotrophic factor receptors, and mRNAs within axons, dendrites, and synapses.
      Recent studies have begun to clarify the mechanisms of cargo selection and
      directional transport in subcellular compartments. Furthermore, molecular
      genetics has revealed unexpected roles for molecular motors in brain wiring,
      neuronal survival, neuronal plasticity, higher brain function, and control of
      central nervous system and peripheral nervous system development. Finally, it is
      also evident that molecular motors are critically involved in neuronal disease
      pathogenesis. Thus, molecular motor research is becoming an exciting frontier of
      neuroscience.

PMID- 21092855
TI  - Single-synapse analysis of a diverse synapse population: proteomic imaging
      methods and markers.
AB  - A lack of methods for measuring the protein compositions of individual synapses
      in situ has so far hindered the exploration and exploitation of synapse molecular
      diversity. Here, we describe the use of array tomography, a new high-resolution
      proteomic imaging method, to determine the composition of glutamate and GABA
      synapses in somatosensory cortex of Line-H-YFP Thy-1 transgenic mice. We find
      that virtually all synapses are recognized by antibodies to the presynaptic
      phosphoprotein synapsin I, while antibodies to 16 other synaptic proteins
      discriminate among 4 subtypes of glutamatergic synapses and GABAergic synapses.
      Cell-specific YFP expression in the YFP-H mouse line allows synapses to be
      assigned to specific presynaptic and postsynaptic partners and reveals that a
      subpopulation of spines on layer 5 pyramidal cells receives both VGluT1-subtype
      glutamatergic and GABAergic synaptic inputs. These results establish a means for
      the high-throughput acquisition of proteomic data from individual cortical
      synapses in situ.

PMID- 21092856
TI  - Sortilin-mediated endocytosis determines levels of the frontotemporal dementia
      protein, progranulin.
AB  - VIDEO ABSTRACT: The most common inherited form of Frontotemporal Lobar
      Degeneration (FTLD) known stems from Progranulin (GRN) mutation and exhibits TDP
      43 plus ubiquitin aggregates. Despite the causative role of GRN
      haploinsufficiency in FTLD-TDP, the neurobiology of this secreted glycoprotein is
      unclear. Here, we examined PGRN binding to the cell surface. PGRN binds to
      cortical neurons via its C terminus, and unbiased expression cloning identifies
      Sortilin (Sort1) as a binding site. Sort1-/- neurons exhibit reduced PGRN
      binding. In the CNS, Sortilin is expressed by neurons and PGRN is most strongly
      expressed by activated microglial cells after injury. Sortilin rapidly
      endocytoses and delivers PGRN to lysosomes. Mice lacking Sortilin have elevations
      in brain and serum PGRN levels of 2.5- to 5-fold. The 50% PGRN decrease causative
      in FTLD-TDP cases is mimicked in GRN+/- mice, and is fully normalized by Sort1
      ablation. Sortilin-mediated PGRN endocytosis is likely to play a central role in
      FTLD-TDP pathophysiology.

PMID- 21092857
TI  - NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in
      postnatal life and following neurodegeneration.
AB  - The mammalian CNS contains a ubiquitous population of glial progenitors known as
      NG2+ cells that have the ability to develop into oligodendrocytes and undergo
      dramatic changes in response to injury and demyelination. Although it has been
      reported that NG2+ cells are multipotent, their fate in health and disease
      remains controversial. Here, we generated PDGFalphaR-CreER transgenic mice and
      followed their fate in vivo in the developing and adult CNS. These studies
      revealed that NG2+ cells in the postnatal CNS generate myelinating
      oligodendrocytes, but not astrocytes or neurons. In regions of neurodegeneration
      in the spinal cord of ALS mice, NG2+ cells exhibited enhanced proliferation and
      accelerated differentiation into oligodendrocytes but remained committed to the
      oligodendrocyte lineage. These results indicate that NG2+ cells in the normal CNS
      are oligodendrocyte precursors with restricted lineage potential and that cell
      loss and gliosis are not sufficient to alter the lineage potential of these
      progenitors.

PMID- 21092858
TI  - The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb
      neurons via crystallin alphaA.
AB  - Most neurons in the adult mammalian brain survive for the entire life of an
      individual. However, it is not known which transcriptional pathways regulate this
      survival in a healthy brain. Here, we identify a pathway regulating neuronal
      survival in a highly subtype-specific manner. We show that the transcription
      factor Pax6 expressed in dopaminergic neurons of the olfactory bulb regulates the
      survival of these neurons by directly controlling the expression of crystallin
      alphaA (CryalphaA), which blocks apoptosis by inhibition of procaspase-3
      activation. Re-expression of CryalphaA fully rescues survival of Pax6-deficient
      dopaminergic interneurons in vivo and knockdown of CryalphaA by shRNA in wild
      type mice reduces the number of dopaminergic OB interneurons. Strikingly, Pax6
      utilizes different DNA-binding domains for its well-known role in fate
      specification and this role of regulating the survival of specific neuronal
      subtypes in the mature, healthy brain.

PMID- 21092859
TI  - Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.
AB  - Coordinated migration of newly born neurons to their prospective target laminae
      is a prerequisite for neural circuit assembly in the developing brain. The
      evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration
      in the mammalian cerebral cortex. The cytoplasmic nature of LIS1 and NDEL1
      proteins suggest that they regulate neuronal migration cell autonomously. Here,
      we extend mosaic analysis with double markers (MADM) to mouse chromosome 11 where
      Lis1, Ndel1, and 14-3-3E (encoding a LIS1/NDEL1 signaling partner) are located.
      Analyses of sparse and uniquely labeled mutant cells in mosaic animals reveal
      distinct cell-autonomous functions for these three genes. Lis1 regulates neuronal
      migration efficiency in a dose-dependent manner, while Ndel1 is essential for a
      specific, previously uncharacterized, late step of neuronal migration: entry into
      the target lamina. Comparisons with previous genetic perturbations of Lis1 and
      Ndel1 also suggest a surprising degree of cell-nonautonomous function for these
      proteins in regulating neuronal migration.

PMID- 21092860
TI  - Bassoon speeds vesicle reloading at a central excitatory synapse.
AB  - Sustained rate-coded signals encode many types of sensory modalities. Some
      sensory synapses possess specialized ribbon structures, which tether vesicles, to
      enable high-frequency signaling. However, central synapses lack these structures,
      yet some can maintain signaling over a wide bandwidth. To analyze the underlying
      molecular mechanisms, we investigated the function of the active zone core
      component Bassoon in cerebellar mossy fiber to granule cell synapses. We show
      that short-term synaptic depression is enhanced in Bassoon knockout mice during
      sustained high-frequency trains but basal synaptic transmission is unaffected.
      Fluctuation and quantal analysis as well as quantification with constrained short
      term plasticity models revealed that the vesicle reloading rate was halved in the
      absence of Bassoon. Thus, our data show that the cytomatrix protein Bassoon
      speeds the reloading of vesicles to release sites at a central excitatory
      synapse.

PMID- 21092861
TI  - Bassoon and the synaptic ribbon organize Ca2+ channels and vesicles to add
      release sites and promote refilling.
AB  - At the presynaptic active zone, Ca2+ influx triggers fusion of synaptic vesicles.
      It is not well understood how Ca2+ channel clustering and synaptic vesicle
      docking are organized. Here, we studied structure and function of hair cell
      ribbon synapses following genetic disruption of the presynaptic scaffold protein
      Bassoon. Mutant synapses--mostly lacking the ribbon--showed a reduction in
      membrane-proximal vesicles, with ribbonless synapses affected more than ribbon
      occupied synapses. Ca2+ channels were also fewer at mutant synapses and appeared
      in abnormally shaped clusters. Ribbon absence reduced Ca2+ channel numbers at
      mutant and wild-type synapses. Fast and sustained exocytosis was reduced,
      notwithstanding normal coupling of the remaining Ca2+ channels to exocytosis. In
      vitro recordings revealed a slight impairment of vesicle replenishment.
      Mechanistic modeling of the in vivo data independently supported morphological
      and functional in vitro findings. We conclude that Bassoon and the ribbon (1)
      create a large number of release sites by organizing Ca2+ channels and vesicles,
      and (2) promote vesicle replenishment.

PMID- 21092862
TI  - Sensing muscle ischemia: coincident detection of acid and ATP via interplay of
      two ion channels.
AB  - Ischemic pain--examples include the chest pain of a heart attack and the leg pain
      of a 30 s sprint--occurs when muscle gets too little oxygen for its metabolic
      need. Lactic acid cannot act alone to trigger ischemic pain because the pH change
      is so small. Here, we show that another compound released from ischemic muscle,
      adenosine tri-phosphate (ATP), works together with acid by increasing the pH
      sensitivity of acid-sensing ion channel number 3 (ASIC3), the molecule used by
      sensory neurons to detect lactic acidosis. Our data argue that ATP acts by
      binding to P2X receptors that form a molecular complex with ASICs; the receptor
      on sensory neurons appears to be P2X5, an electrically quiet ion channel.
      Coincident detection of acid and ATP should confer sensory selectivity for
      ischemia over other conditions of acidosis.

PMID- 21092863
TI  - Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the
      induction of intrinsic plasticity.
AB  - In visual cortex monocular deprivation (MD) during a critical period (CP) reduces
      the ability of the deprived eye to activate cortex, but the underlying cellular
      plasticity mechanisms are incompletely understood. Here we show that MD reduces
      the intrinsic excitability of layer 5 (L5) pyramidal neurons and enhances long
      term potentiation of intrinsic excitability (LTP-IE). Further, MD and LTP-IE
      induce reciprocal changes in K(v)2.1 current, and LTP-IE reverses the effects of
      MD on intrinsic excitability. Taken together these data suggest that MD reduces
      intrinsic excitability by preventing sensory-drive induced LTP-IE. The effects of
      MD on excitability were correlated with the classical visual system CP, and (like
      the functional effects of MD) could be rapidly reversed when vision was restored.
      These data establish LTP-IE as a candidate mechanism mediating loss of visual
      responsiveness within L5, and suggest that intrinsic plasticity plays an
      important role in experience-dependent refinement of visual cortical circuits.

PMID- 21092865
TI  - Human posterior parietal cortex flexibly determines reference frames for reaching
      based on sensory context.
AB  - Current models of sensorimotor transformations emphasize the dominant role of
      gaze-centered representations for reach planning in the posterior parietal cortex
      (PPC). Here we exploit fMRI repetition suppression to test whether the sensory
      modality of a target determines the reference frame used to define the motor goal
      in the PPC and premotor cortex. We show that when targets are defined visually,
      the anterior precuneus selectively encodes the motor goal in gaze-centered
      coordinates, whereas the parieto-occipital junction, Brodman Area 5 (BA 5), and
      PMd use a mixed gaze- and body-centered representation. In contrast, when targets
      are defined by unseen proprioceptive cues, activity in these areas switches to
      represent the motor goal predominantly in body-centered coordinates. These
      results support computational models arguing for flexibility in reference frames
      for action according to sensory context. Critically, they provide neuroanatomical
      evidence that flexibility is achieved by exploiting a multiplicity of reference
      frames that can be expressed within individual areas.

PMID- 21092864
TI  - Bidirectional plasticity gated by hyperpolarization controls the gain of
      postsynaptic firing responses at central vestibular nerve synapses.
AB  - Linking synaptic plasticity with behavioral learning requires understanding how
      synaptic efficacy influences postsynaptic firing in neurons whose role in
      behavior is understood. Here, we examine plasticity at a candidate site of motor
      learning: vestibular nerve synapses onto neurons that mediate reflexive
      movements. Pairing nerve activity with changes in postsynaptic voltage induced
      bidirectional synaptic plasticity in vestibular nucleus projection neurons: long
      term potentiation relied on calcium-permeable AMPA receptors and postsynaptic
      hyperpolarization, whereas long-term depression relied on NMDA receptors and
      postsynaptic depolarization. Remarkably, both forms of plasticity uniformly
      scaled synaptic currents evoked by pulse trains, and these changes in synaptic
      efficacy were translated into linear increases or decreases in postsynaptic
      firing responses. Synapses onto local inhibitory neurons were also plastic but
      expressed only long-term depression. Bidirectional, linear gain control of
      vestibular nerve synapses onto projection neurons provides a plausible mechanism
      for motor learning underlying adaptation of vestibular reflexes.

PMID- 21092866
TI  - Coding of reward risk by orbitofrontal neurons is mostly distinct from coding of
      reward value.
AB  - Risky decision-making is altered in humans and animals with damage to the
      orbitofrontal cortex. However, the cellular function of the intact orbitofrontal
      cortex in processing information relevant for risky decisions is unknown. We
      recorded responses of single orbitofrontal neurons while monkeys viewed visual
      cues representing the key decision parameters, reward risk and value. Risk was
      defined as the mathematical variance of binary symmetric probability
      distributions of reward magnitudes; value was defined as non-risky reward
      magnitude. Monkeys displayed graded behavioral preferences for risky outcomes, as
      they did for value. A population of orbitofrontal neurons showed a distinctive
      risk signal: their cues and reward responses covaried monotonically with the
      variance of the different reward distributions without monotonically coding
      reward value. Furthermore, a small but statistically significant fraction of risk
      responses also coded reward value. These risk signals may provide physiological
      correlates for the role of the orbitofrontal cortex in risk processing.

PMID- 21092867
TI  - Lessons from the animal kingdom.

PMID- 21092868
TI  - Bone consequences of high dietary phosphate.

PMID- 21092869
TI  - Three-tesla diffusion tensor imaging of Meyer's loop by tractography, color-coded
      fractional anisotropy maps, and eigenvectors.
AB  - The aim of this study was to evaluate Meyer's loop by 3-T MRI with fiber
      tractography, color-coded fractional anisotropy maps, and eigenvector maps. The
      anteroposterior distance from the anterior bundle of the Meyer's loop to temporal
      pole ranged from 26.3 to 34 mm, overlapping with the previously published
      anatomical dissection studies. Diffusion tensor imaging with fiber tractography,
      color-coded FA maps, and color maps of the principal eigenvector at 3 T appear to
      be promising techniques for the virtual dissection of Meyer's loop.

PMID- 21092870
TI  - CAD in full-field digital mammography-influence of reader experience and
      application of CAD on interpretation of time.
AB  - AIM: To assess time expenditure using the influence of computer-assisted
      detection (CAD) system in the interpretation of the dependence of early research
      and benign and malignant mammograms on readers' experience. MATERIALS AND
      METHODS: CAD (Image Checker V2.3; R2 Technology, Los Altos, CA, USA) was
      prospectively applied on digital mammograms of 303 patients [early research
      (n=103), benign (n=102), and malignant group (n=98)]. Mammograms were analyzed by
      three readers with varying experience in evaluating mammograms (medical student,
      resident and attending) according to the BI-RADS classification. Time was stopped
      and recorded. All images were presented randomly with and without the influence
      of CAD and from the different patient groups. To evaluate the statistical
      significance, the corresponding P value for time to read the mammograms in
      addition to different patient groups, application of CAD, readers' experience,
      and interaction of reader was calculated. RESULTS: The attending needs,
      independent of CAD application, the least time, followed by the medical assistant
      and the student. In all three patient groups, CAD adoption elongates reading time
      of the student and the resident. The medical specialist needs with and without
      CAD median the same time. In the early research group, no significant differences
      were registered (P=.1343). Concerning readers' experience, there is an explicit
      significant difference (P<.0001). The application of CAD correlates with the
      corresponding readers' experience and also provides a not significant result. In
      comparison, the P value for the malignant and benign groups shows significant
      interactions between the readers' experiences as well as CAD application.
      CONCLUSION: The future role of CAD application depends on whether sensitivity can
      be increased and time expenditure caused by false-positive marks can be
      decreased. In the future, second reading could be substituted by a CAD system if
      the reader has a wide professional experience.

PMID- 21092871
TI  - Multidetector CT findings of right intrahepatic portosystemic venous shunt.
AB  - PURPOSE: To evaluate multidetector CT features of right intrahepatic
      portosystemic venous shunt (IPSVS). MATERIALS AND METHODS: Pathways of right
      IPSVS were evaluated from 20 patients. Diameters of right portal veins were
      measured in IPSVS patients, 30 cirrhotic and 30 healthy patients. RESULT: Among
      22 IPSVSs, shunt between posterior branch and inferior phrenic vein was most
      common. Diameters of the posterior branch were larger in IPSVS patients than in
      other groups. CONCLUSION: Most right IPSVSs drain to inferior phrenic vein
      through dilated posterior branch.

PMID- 21092872
TI  - Diffusion-weighted MRI with parallel imaging technique: apparent diffusion
      coefficient determination in normal kidneys and in nonmalignant renal diseases.
AB  - The purpose of the study was to assess the capability and the reliability of
      apparent diffusion coefficient (ADC) measurements in the evaluation of different
      benign renal abnormalities. Twenty-five healthy volunteers and 31 patients,
      divided into seven different groups (A-G) according to pathology, underwent
      diffusion-weighted magnetic resonance imaging (DW MRI) of the kidneys using 1.5-T
      system. DW images were obtained in the axial plane with a spin-echo echo planar
      imaging single-shot sequence with three b values (0, 300, and 600 s/mm2). Before
      acquisition of DW sequences, we performed in each patient a morphological study
      of the kidneys. ADC was 2.40+/-0.20*10-3 mm2 s-1 in volunteers. A significant
      difference was found between Groups A (cysts=3.39+/-0.51*10-3 mm2 s-1) and B
      (acute/chronic renal failure=1.38+/-0.40*10-3 mm2 s-1) and between Groups A and C
      (chronic pyelonephritis=1.53+/-0.21*10-3 mm2 s-1) (P<.05). An important
      difference was also observed among Group D (hydronephrosis=4.82+/-0.35*10-3 mm2 s
      1) and Groups A, B, and C (P<.05), whereas no differences were found between
      Groups B and C (P>.05). A considerable correlation between glomerular filtration
      rate and ADC was found (P=.04). In conclusion, significant differences were
      detected among different patient groups, and this suggests that ADC measurements
      can be useful in differentiating normal renal parenchyma from most commonly
      encountered nonmalignant renal lesions.

PMID- 21092873
TI  - Preoperative staging of renal cell carcinoma using magnetic resonance imaging:
      comparison with pathological staging.
AB  - We have retrospectively assessed the accuracy of our MRI protocol on 1.0-T MRI
      system for preoperative staging of renal cell carcinoma using the 2002 TNM
      staging system and pathological staging as the gold standard. Medical records of
      48 patients (mean age, 56.28 years) with 57 renal tumors were reviewed: 52
      malignant renal tumors were found; most of the patients were staged T1N0M0. In
      our study, kappa test revealed excellent agreement between all three classes of
      the TNM staging system.

PMID- 21092874
TI  - Appearance of primary lymphoid malignancies on lymphotropic nanoparticle-enhanced
      magnetic resonance imaging using ferumoxtran-10.
AB  - Patients with pathologically confirmed lymphoma/leukemia were retrospectively
      identified from a large single-institution phase III clinical trial with
      ferumoxtran-10. Five (2.3%) of 220 patients had lymphoid malignancies involving
      lymph nodes. A subset of patients (n=27) with biopsy-proven nodal metastases from
      genitourinary or breast cancer was selected as control group. Ferumoxtran-10
      enhancement patterns and signal-to-noise ratios of lymph nodes involved by
      metastases and lymphoid malignancy were assessed. Like nodal metastases, nodes
      involved by lymphoid malignancies demonstrate persistent high T2*-signal
      intensity on lymphotropic nanoparticle-enhanced magnetic resonance imaging.

PMID- 21092875
TI  - MRI features of lipoblastoma: differentiating from other palpable lipomatous
      tumor in pediatric patients.
AB  - The purpose of this study was to describe the magnetic resonance imaging (MRI)
      features of lipoblastomas in pediatric patients and to differentiate them from
      other palpable benign lipomatous tumors. The relatively specific MRI features of
      nonenhancing cystic change and enhancing soft tissue nodules seen in lipoblastoma
      may help to differentiate it from other types of lipomatous tumor in pediatric
      patients.

PMID- 21092876
TI  - Nutritional secondary hyperparathyroidism in the animal kingdom: report of two
      cases.
AB  - This report describes two cases of marked bone loss (osteopenia) occurring in a 9
      week-old German shepherd puppy and in a 6-month-old tiger. In both cases the
      animals were fed a diet which was exclusively boneless meat. The diets in both
      cases contained approximately 40 mg of calcium and 1000 mg of phosphorus per
      pound resulting in both calcium deficiency and phosphorus excess, resulting in a
      phosphorus-to-calcium ratio of 25:1, well beyond the amounts known to cause
      marked loss of bone experimentally. This has been termed nutritional secondary
      hyperparathyroidism (NSH). Both animals presented with severe bone pain,
      difficulty in ambulation, and difficulty in chewing food. Radiographs showed
      marked osteopenia and spontaneous fractures. Both responded clinically and
      radiographically to calcium supplementation and a diet with an appropriate
      phosphorus-to-calcium ratio. The importance of calcium and phosphorus in the
      human diet is briefly discussed.

PMID- 21092877
TI  - Infiltrating syringomatous adenoma presenting as microcalcification in the nipple
      on screening mammogram: case report and review of the literature of radiologic
      features.
AB  - Infiltrating syringomatous adenoma (ISA) of the nipple, first described by Rosen
      in 1983 (Am J Surg Pathol, 1983, 7, 739-745), is a rare benign tumor that can be
      misdiagnosed as a malignancy. ISA is characterized by its specific location in
      the subareolar region, its distinct histologic appearance resembling sweat duct
      or syringomatous tumors, and its locally infiltrating growth. We describes a case
      of ISA of the nipple presenting as microcalcification that was found on screening
      mammography. We also reviewed previously reported radiologic features of ISA.

PMID- 21092878
TI  - Radiology-Pathology Conference: Mature teratoma arising from an intra-abdominal
      undescended testis in a 7-month-old infant.
AB  - We report a rare case of an intra-abdominal testicular mature teratoma in a 7
      month-old male infant presenting with a palpable abdominal mass and unilateral
      undescended testis. We describe the pathology, clinical presentation, and imaging
      findings of this entity. Clinical features accompanied by characteristic
      radiologic findings guide a provisional diagnosis that is confirmed by histologic
      analysis following surgical removal of the tumor. The pathogenesis and radiologic
      findings of testicular mature teratomas in the prepubertal population share many
      similarities to that of mature ovarian teratomas commonly seen in females of
      reproductive age. Awareness of this entity will permit the radiologist to suggest
      timely diagnosis and intervention when presented with a similar case.

PMID- 21092879
TI  - Polysplenia syndrome accompanied with situs inversus totalis and annular pancreas
      in an elderly patient.
AB  - Polysplenia syndrome (PS) is rarely encountered in elderly. It is characterized
      by multiple spleens associated with various cardiac and gastrointestinal
      abnormalities including partial or complete agenesis of dorsal pancreas. Situs
      inversus totalis (SIT) is a rare congenital anomaly with mirror image of viscera
      combined with dextrocardia. Occurrence of SIT and PS in the same patient is
      exceedingly rare. We present the first case of adult PS with SIT accompanied with
      annular pancreas.

PMID- 21092880
TI  - Non-Hodgkin's lymphoma of the bone and the liver without lymphadenopathy revealed
      on FDG-PET/CT.
AB  - Primary extranodal lymphomas are much less frequent than nodal lymphomas. Osseous
      and hepatic lymphomas commonly present with additional nodal lesions. Primary
      lymphoma of the bone or of the liver without nodal disease is uncommon. We
      describe a case of extranodal non-Hodgkin's lymphoma with numerous osseous and
      hepatic lesions without any lymph node involvement on FDG-PET/CT images. This is
      the first report of the coexistence of both osseous and hepatic lymphoma in the
      same patient without any lymph node involvement.

PMID- 21092881
TI  - Letter-Krook.

PMID- 21092883
TI  - Pulsatile left ventricular assist devices: what is the role in the modern era?
AB  - With the widespread use of continuous-flow ventricular assist devices (VADs), the
      role of pulsatile VADs remain in question. In acute cardiogenic shock, pulsatile
      VADs maximize perfusion pressure, restore end organ perfusion, and maximally
      unload the pulmonary circulation and right heart. In addition, pulsatile left
      VADs allow for easy conversion to biventricular support using one platform, in
      the case of acute right ventricular failure. Pulsatile VADs still have a major
      role in the treatment of acute cardiogenic shock.

PMID- 21092884
TI  - Frailty: the missing element in predicting operative mortality.
AB  - Although age is an extensively documented independent risk factor for mortality,
      morbidity and decreased quality of life after cardiac surgery, it has also been
      demonstrated that excellent outcomes can be obtained after cardiac surgery in
      very elderly patients. The disparity between chronological and biological age
      that underlies these findings forms the focus of this review, which examines
      recent studies aiming to refine pre-operative risk stratification tools by using
      assessments of frailty and functional status.

PMID- 21092885
TI  - Professionalism in medicine: are we closer to unifying principles?
AB  - The enhancement of professionalism in surgery and medicine is an important goal
      for all healthcare providers, both at the individual level of the physician and
      at the large-scale level of the healthcare system. Recently, much has been
      written about the challenges in implementing the concept of professionalism
      within healthcare delivery. The dilemma of ensuring a uniform commitment to
      professional behavior from all physicians has gained particular attention. In a
      unique approach, Lucey and Souba advocate for addressing the problem of lapses in
      professionalism as a form of medical error. This perspective may provide a fresh
      outlook on the problem.

PMID- 21092886
TI  - Video-assisted thoracoscopic surgical lobectomy: the potential oncological
      benefit of surgical immunomodulation.

PMID- 21092887
TI  - Lung cancer outcomes: the effects of socioeconomic status and race.

PMID- 21092888
TI  - "Personalizing" therapy for non-small cell lung cancer.
AB  - The sequencing of the human genome has lead to an even greater understanding of
      the genetic basis of numerous diseases. During the past several years, genetic
      approaches to a number of solid organ malignancies, including non-small cell lung
      cancer, have lead us to an increased understanding of the disrupted genetic
      pathways involved in tumor initiation and progression. Two recent articles are
      reviewed that highlight the broad potential for successful targeted therapy in
      thoracic malignancies.

PMID- 21092889
TI  - Blood conservation in cardiac surgery: let's get restrictive.
AB  - Despite increasing evidence suggesting harmful effects of blood transfusions,
      physician practices are slow to change. A systematic approach is required to
      successfully minimize the need for red cell transfusions in the perioperative
      cardiac surgical patient. This involves preoperative, intraoperative, and
      postoperative strategies to minimize blood loss and maximize blood conservation.
      In addition it requires physician education regarding the potential deleterious
      effects of blood and the more recent evidence that restrictive transfusion
      strategies are safe and possibly beneficial to postoperative surgical outcomes.
      In this article, we review the data with respect to blood transfusions in cardiac
      surgery patients as well as management strategies to minimize the need for blood
      transfusions in the perioperative period.

PMID- 21092891
TI  - Vasoplegia during cardiac surgery: current concepts and management.
AB  - Vasoplegic syndrome (VS) is a recognized and relatively common complication of
      cardiopulmonary bypass (CPB), appearing with an incidence ranging between 5% and
      25%. It is characterized by significant hypotension, high or normal cardiac
      outputs and low systemic vascular resistance (SVR), and increased requirements
      for fluids and vasopressors during or after CPB. Patients developing VS are at
      increased risk for death and other major complications following cardiac surgery.
      This review will focus on the pathophysiology and contemporary strategies of
      treating VS encountered after CPB.

PMID- 21092892
TI  - Interventional valve surgery: building a team and working together.
AB  - Transcatheter aortic valve implantation (TAVI) is a new modality that may change
      the therapeutic landscape in the management of aortic valve stenosis. Despite the
      excellent results of surgical aortic valve replacement, TAVI has the potential to
      revolutionize the treatment of elderly and high-risk patients with aortic
      stenosis. It therefore constitutes a new reality that cardiac surgeons have to
      acknowledge. As TAVI indications and techniques become better defined, the
      importance of a team approach to the implementation and performance of TAVI is
      becoming increasingly evident. The surgeon has a crucial role to play in the
      introduction, development, and sustainability of TAVI at any institution. In this
      article, we discuss the procedural technique involved in TAVI, as well as the
      cardiologist and heart surgeon individualities and team dynamics. We make a case
      for judicious team-based adoption of TAVI technologies, considering that evidence
      based and health economics data are not yet available. We also illustrate how a
      team approach may lead to improved outcomes, better patient and institutional
      acceptance, and a better definition of the therapeutic niche of TAVI modalities,
      amid the excellent results of conventional aortic valve replacement surgery.

PMID- 21092893
TI  - Relevance of endobronchial ultrasonography to thoracic surgeons.
AB  - The relevance of endobronchial ultrasonography (EBUS) to thoracic surgeons is 2
      fold: first, EBUS is an accurate and versatile diagnostic tool; second, EBUS is
      of importance to our specialty. The diagnostic performance of endobronchial
      ultrasonography (EBUS) is similar to that of mediastinoscopy, except for a lower
      negative predictive value for EBUS. Consequently, EBUS does not replace
      mediastinoscopy, but instead EBUS and mediastinoscopy are complementary. A
      thoracic surgeon proficient in EBUS has the ability to decide which tool or
      combination of tools to use to optimize patient care. The relevance of EBUS can
      be described in evolutionary terms: proficiency in EBUS exemplifies a new trait
      that can enhance our adaptability to the current environment. An indirect measure
      of the acquisition of this new skill by our specialty can be gleaned from an
      overview of original EBUS publications: nearly one-half are authored or
      coauthored by thoracic surgeons. EBUS is an excellent diagnostic tool available
      to thoracic surgeons to optimize patient care and an example of a skill that may
      enhance our survival as a surgical specialty.

PMID- 21092890
TI  - Cardiac gene therapy.
AB  - Heart failure is a chronic progressive disorder in which frequent and recurrent
      hospitalizations are associated with high mortality and morbidity. The incidence
      and the prevalence of this disease will increase with the increase in the number
      of the aging population of the United States. Understanding the molecular
      pathology and pathophysiology of this disease will uncover novel targets and
      therapies that can restore the function or attenuate the damage of malfunctioning
      cardiomyocytes by gene therapy that becomes an interesting and a promising field
      for the treatment of heart failure as well as other diseases in the future. Of
      equal importance are developing vectors and delivery methods that can efficiently
      transduce most of the cardiomyocytes that can offer a long-term expression and
      that can escape the host immune response. Recombinant adeno-associated virus
      vectors have the potential to become a promising novel therapeutic vehicles for
      molecular medicine in the future.

PMID- 21092894
TI  - Esophageal preservation in the setting of high-grade dysplasia and superficial
      cancer.
AB  - The principle treatment for high-grade dysplasia and superficial esophageal
      cancer is considered esophagectomy. However, novel technologies and innovations
      in technique have enabled esophageal preservation by endoscopic management in
      select patients. The concepts and evidence pertaining to esophageal preservation
      in early stage malignancy are reviewed in detail. A treatment algorithm based
      upon the current evidence surrounding esophageal preservation is presented.

PMID- 21092895
TI  - Tracheobronchomalacia in adults.
AB  - Severe, diffuse tracheobronchomalacia (TBM) is an underrecognized cause of
      dyspnea, recurrent respiratory infections, cough, secretion retention, and even
      respiratory insufficiency. Patients often have comorbidities, such as asthma or
      chronic obstructive pulmonary disease, and inappropriate treatment for these
      conditions may precede eventual recognition of TBM by months or years. Most of
      these patients have an acquired form of TBM in which the etiology in unknown.
      Diagnosis of TBM is made by airway computed tomography scan and flexible
      bronchoscopy with forced expiration. The prevailing definition of TBM as a 50%
      reduction in cross-sectional area is nonspecific, with a high proportion of
      healthy volunteers meeting this threshold. The clinically significant threshold
      is complete or near-complete collapse of the airway. Airway stenting may treat
      TBM, although complications resulting from indwelling prostheses often limit the
      durability of stents. Surgical stabilization of the airway by posterior splinting
      (tracheobronchoplasty) effectively and permanently corrects malacic airways.
      Proper surgical selection is facilitated by a short-term stent trial.

PMID- 21092896
TI  - Repair of bileaflet prolapse in Barlow syndrome.
AB  - Mitral valve (MV) leaflet billowing, prolapse, and excessive tissue are hallmarks
      of Barlow syndrome. Successful MV repair can be a challenge in these oftentimes
      young and otherwise healthy patients. We herein present details on our stepwise
      approach to MV repair for Barlow syndrome including: (1) surgical approach; (2)
      MV exposure; (3) assessment of MV pathology; (4) repair of leaflet prolapse; (5)
      choice and sizing of annuloplasty ring; and (6) fine-tuning and troubleshooting.
      Our repair strategy involves extensive use of Gore-Tex neochordae using the so
      called "loop technique." We have used this operative strategy via a right mini
      thoracotomy in 436 patients with bileaflet prolapse and 144 patients with Barlow
      syndrome. Our successful MV repair rate is 95% in patients with Barlow syndrome
      and the ten-year freedom from reoperation rate is 96% for such patients. We can
      conclude that a stepwise approach to this MV pathology with extensive use of the
      loop technique can result in very acceptable outcomes, even in patients
      undergoing minimal invasive surgery.

PMID- 21092897
TI  - Bileaflet repair for barlow syndrome.

PMID- 21092898
TI  - Laparoscopic myotomy and fundoplication for achalasia.

PMID- 21092899
TI  - New technique for Heller myotomy with the LigaSure device alone.

PMID- 21092900
TI  - Right coronary artery injury after tricuspid valve repair.

PMID- 21092901
TI  - Visual perception of effervescence in champagne and other sparkling beverages.
AB  - The so-called effervescence process, which enlivens champagne, sparkling wines,
      beers, and carbonated beverages in general, is the result of the fine interplay
      between CO2-dissolved gas molecules, tiny air pockets trapped within microscopic
      particles during the pouring process, and some liquid properties. This chapter
      summarizes recent advances obtained during the last decade concerning the
      physicochemical processes behind the nucleation, rise, and burst of bubbles found
      in glasses poured with sparkling beverages. Those phenomena observed in close-up
      through high-speed photography are often visually appealing. Moreover, the
      kinetics of gas discharging from freshly poured glasses was monitored with time,
      whether champagne is served into a flute or into a coupe. The role of temperature
      was also examined. We hope that your enjoyment of champagne will be enhanced
      after reading this fully illustrated review dedicated to the deep beauties of
      nature often hidden behind many everyday phenomena.

PMID- 21092902
TI  - Chemometric brains for artificial tongues.
AB  - The last years showed a significant trend toward the exploitation of rapid and
      economic analytical devices able to provide multiple information about samples.
      Among these, the so-called artificial tongues represent effective tools which
      allow a global sample characterization comparable to a fingerprint. Born as taste
      sensors for food evaluation, such devices proved to be useful for a wider number
      of purposes. In this review, a critical overview of artificial tongue
      applications over the last decade is outlined. In particular, the focus is
      centered on the chemometric techniques, which allow the extraction of valuable
      information from nonspecific data. The basic steps of signal processing and
      pattern recognition are discussed and the principal chemometric techniques are
      described in detail, highlighting benefits and drawbacks of each one.
      Furthermore, some novel methods recently introduced and particularly suitable for
      artificial tongue data are presented.

PMID- 21092904
TI  - Microoxidation in wine production.
AB  - Microoxygenation (MOX) is now widely applied for the maturation of red wines as
      an alternative to barrel aging. The proposed improvements in wine quality arising
      from MOX include color stabilization, removal of unwanted off-odors, and
      improvements in wine mouthfeel. In this review, an outline is provided of
      oxygenation systems, particularly microbullage and polymer membrane delivery, and
      of the current understanding of wine oxidation processes. A summary of the
      results from published studies into red wine MOX is then provided, beginning with
      observations on O(2) and acetaldehyde accumulation, and the moderating effect of
      added sulfur dioxide. Effects upon red wine color, particularly the more rapid
      formation of polymeric pigments and higher color retention, have been
      consistently demonstrated in MOX studies, along with further effects on specific
      polyphenol compounds. A few reports have recently examined the effect of MOX on
      red wine aromas, but these have yet to identify compounds that consistently
      change in a manner that would explain sensory observations regarding a lowering
      of herbaceous and reductive odors. Likewise, tannin analyses have been undertaken
      in several studies, but explanations of the decline in wine astringency remain to
      be developed. The accelerated growth of unwanted microorganisms has also been
      examined in a limited number of studies, but no major problems have been
      identified in this area.

PMID- 21092903
TI  - Photodynamic treatment: a new efficient alternative for surface sanitation.
AB  - A novel and promising technology-photodynamic treatment (PDT), aimed for surface
      cleaning and sanitation in food industry-is presented. It is based on the
      treatment of surfaces with nontoxic dyes (photosensitizers), followed by
      illumination of the surface with regular white light. The method is currently
      used in the medical field and was proved to have wide specificity against a
      variety of bacterial and viral pathogens as well as against yeasts and protozoa.
      An additional advantage of this approach is that development of resistance of
      microorganisms to PDT was shown to be unlikely. The theoretical basis of light
      induced antimicrobial treatment is described, followed by examples of its
      application for the cleaning and disinfection of surfaces. All available
      information supports the idea that PDT could offer a very efficient and cost
      effective way to combat microbial contamination of foods. The advantages and
      pitfalls of the technique are discussed. Directions of future research needed for
      bringing the technology to commercial reality are identified.

PMID- 21092905
TI  - The morama bean (Tylosema esculentum): a potential crop for southern Africa.
AB  - The morama bean is an underutilized leguminous oilseed native to the Kalahari
      Desert and neighboring sandy regions of Botswana, Namibia, and South Africa
      (Limpopo, North-West, Gauteng, and Northern Cape provinces), and forms part of
      the diet of the indigenous population in these countries. It is also known as
      gemsbok bean, moramaboontjie, elandboontjie, braaiboonjie, marama, marumana, tsi,
      tsin, gami, and ombanui. It is reported as an excellent source of good quality
      protein (29-39%); its oil (24-48%) is rich in mono- and di-unsaturated fatty
      acids and contains no cholesterol. Morama is a good source of micronutrients such
      as calcium, iron, zinc, phosphate, magnesium, and B vitamins including folate. It
      is also reported to be a potential source of phytonutrients including phenolic
      compounds (e.g., tannins), trypsin inhibitors, phytates, and oligosaccharides,
      components which have been shown in other foods to contribute to health in
      particular, prevention of noncommunicable diseases such as cardiovascular
      diseases, diabetes, and some cancers. From a nutritional and health perspective,
      the morama bean has potential commercial value as a cash crop and value-added
      products, particularly in the communities where it is found.

PMID- 21092906
TI  - Foreword: Beam me up, Scotty.

PMID- 21092907
TI  - Preface. The era of telepsychiatry.

PMID- 21092908
TI  - Telepsychiatry in private practice.
AB  - Telepsychiatry is being increasingly adopted in private practice and is predicted
      to play an important role in increasing access to care in rural communities and
      other underserved areas. With the current level of need, it is unlikely that all
      of the required services can be fully met through existing telepsychiatry
      practitioners. Thus, in light of this new research and the significant needs of
      rural communities, some of the historical barriers to using telepsychiatry in
      private practice can be overcome through the use of new technology and sound
      financial modeling. This article examines historical barriers to adopting
      telepsychiatry in private practice and offers adaptations based on a large case
      series derived from the clinical practice of the author as well as a review of
      scientific literature on telepsychiatry.

PMID- 21092909
TI  - Child and youth telepsychiatry in rural and remote primary care.
AB  - Young people with psychological or psychiatric problems are managed largely by
      primary care practitioners, many of whom feel inadequately trained, ill equipped,
      and uncomfortable with this responsibility. Accessing specialist pediatric and
      psychological services, often located in and near large urban centers, is a
      particular challenge for rural and remote communities. Live interactive
      videoconferencing technology (telepsychiatry) presents innovative opportunities
      to bridge these service gaps. The TeleLink Mental Health Program at The Hospital
      for Sick Children in Toronto offers a comprehensive, collaborative model of
      enhancing local community systems of care in rural and remote Ontario using
      videoconferencing. With a focus on clinical consultation, collaborative care,
      education and training, evaluation, and research, ready access to pediatric
      psychiatrists and other specialist mental health service providers can
      effectively extend the boundaries of the medical home. Medical trainees in urban
      teaching centers are also expanding their knowledge of and comfort level with
      rural mental health issues, various complementary service models, and the
      potentials of videoconferencing in providing psychiatric and psychological
      services. Committed and enthusiastic champions, a positive attitude, creativity,
      and flexibility are a few of the necessary attributes ensuring viability and
      integration of telemental health programs.

PMID- 21092910
TI  - Urban telepsychiatry: uncommon service for a common need.
AB  - Psychiatry is a particularly good specialty to provide by telemedicine. The
      psychiatric interaction translates very well to the interactive video medium and
      typically does not require any peripheral medical devices for the consultation
      compared with other specialties. Although telemedicine is most often thought of
      as strictly a rural health tool for solving health care shortages, it has
      sometimes been used to improve access to many health specialists in urban areas
      of the United States. An urban infrastructure can be more supportive of
      telehealth from technical and clinical support perspectives, particularly in
      special or emergent situations. This article highlights the Kansas practice and
      reviews other urban applications of telepsychiatry.

PMID- 21092911
TI  - Bridging the divide between child psychiatry and primary care: the use of
      telephone consultation within a population-based collaborative system.
AB  - The Massachusetts Child Psychiatry Access Project is a public system for
      improving access to care for children with mental health problems in which the
      provision of telephone consultation by child psychiatry teams to pediatric
      primary care providers (PCPs) plays a central role. In this article, the practice
      of telephone consultation within this system is explored through the examination
      of case studies, demonstrating its use in common clinical scenarios. The
      telephone consultations provide immediate case-based clinical education, and also
      serve as a gateway for the provision of as-needed direct child psychiatry
      evaluation and care coordination services. Most importantly, the telephone
      consultations build sustaining collaborative relationships, enhancing the ability
      of PCPs to meet the needs of children with mental health problems.

PMID- 21092912
TI  - The use of telemedicine in pediatric psychology: research review and current
      applications.
AB  - Several novel technologies have long been used in pediatric psychology. From
      using electronic pill-count bottles to track child adherence to pill-taking
      regimens to using bed alarms for night time enuresis, psychologists have relied
      on technology in their work with children who are ill. Much of the recent
      technology literature in pediatric psychology has focused on the use of the
      Internet and other Web-based technologies. This article thoroughly reviews the
      literature regarding telehealth in the field of pediatric psychology, more
      specifically the application of televideo or teleconferencing in various
      populations of children and adolescents with chronic illnesses, followed by the
      authors' clinical and research applications of telehealth in pediatric
      psychology. The review concludes with a summary of study findings and future
      directions in the field for clinicians and researchers alike.

PMID- 21092913
TI  - Telepsychology: research and practice overview.
AB  - There are significant workforce shortages for psychologists with expertise in
      evidence-supported therapies with children, particularly in nonmetropolitan
      areas. Telepsychology, or psychology services delivered by real-time
      videoconferencing, helps bridge this access gap. This article first reviews the
      telepsychology literature and then builds on early telepsychology guidance for
      the current practice environment. The practicalities of telepsychology
      implementation and the lessons drawn from the more well-established
      telepsychiatry practice are described. The authors also provide an update to
      pioneering interdisciplinary telehealth principles presented a decade ago.

PMID- 21092914
TI  - Telepsychiatry and school mental health.
AB  - The provision of mental health services in schools has been one effective
      strategy for reaching out to a greater number of youth to identify and provide
      treatment for mental health issues. With the increasing challenges related to
      shortages in child and adolescent psychiatrists, it is critical to develop models
      of care that can maximize a full range of mental health services for all children
      and adolescents who need them. Telehealth offers an innovative distance
      technology strategy to effectively and efficiently provide access to psychiatric
      services in schools. Telepsychiatry has the potential to better link and enhance
      the provision of health services, and can be particularly beneficial in
      addressing geographic distance and/or capacity issues. This article describes the
      clinical, educational, and administrative uses of telemental health in the school
      environment with mental health professionals and staff.

PMID- 21092915
TI  - Telepsychiatry for children with developmental disabilities: applications for
      patient care and medical education.
AB  - Telemedicine is able to provide specialized care to rural patients with limited
      access. The developmentally disabled population is highly suited to this modality
      and can be seen in general and specialized clinics. The collaborative care model,
      which is useful for this population, provides ongoing collaboration with both the
      local primary care provider and the local treatment team. Telepsychiatry can be
      used for education of trainees working together with an attending physician.
      These clinics can become exceptional opportunities to provide exposure to the
      specialty of child psychiatry for young doctors in training. As new programs
      develop, telepsychiatry for treatment and telepsychiatry for training should go
      hand in hand.

PMID- 21092916
TI  - Telepsychiatry in juvenile justice settings.
AB  - Telepsychiatry is emerging as a valuable means of providing mental health care in
      juvenile justice settings. Youth in the juvenile justice system have high levels
      of psychiatric morbidity. State and local juvenile justice systems frequently
      struggle to provide specialized psychiatric care, as these systems have limited
      resources and often operate in remote locations. Case studies in the use of
      telepsychiatry to provide improved care in juvenile corrections in 4 states are
      described, along with a review of advantages and disadvantages of telepsychiatry
      in these settings.

PMID- 21092917
TI  - Bridging cultures: child psychiatry via videoconferencing.
AB  - Although telepsychiatry can increase access to care for underserved populations,
      its use presents challenges to practicing culturally competent care, especially
      when high degrees of cultural disparity exist between the psychiatrist and the
      patient and/or family. Psychiatrists delivering care from a distance may be
      challenged to understand the health beliefs and practices of the local community
      as well as the social and community settings of clients from different cultural
      backgrounds. Similarly, because providing services via telepsychiatry typically
      requires the involvement of different health care organizations, bridging
      distinct institutional cultures can challenge the effective delivery of services.
      Cultural awareness and sensitivity from the telepsychiatrist are prerequisites
      for helping culturally diverse and remote-dwelling patients to access quality
      care. This article elucidates cultural challenges encountered in the practice of
      telepsychiatry and offers suggestions for how to deal with them.

PMID- 21092919
TI  - Research in child and adolescent telemental health.
AB  - Over the past decade telepsychiatry, and more broadly telemental health (TMH),
      services with children and adolescents have been implemented with diverse
      populations in many geographic areas across the United States. The feasibility
      and acceptability of child and adolescent TMH have been well demonstrated, but
      little research exists on the efficacy and effectiveness of TMH in improving the
      mental health care and outcomes for underserved youth. This article summarizes
      the state of research in child and adolescent telemental health TMH and examines
      studies in other areas of telemedicine that may inspire and guide child and
      adolescent telepsychiatrists to collect data on the process and outcomes of their
      own work.

PMID- 21092920
TI  - Risk management in health care and medical education.

PMID- 21092918
TI  - Telemental health and web-based applications in children and adolescents.
AB  - The authors conducted a review of the literature with regard to child and
      adolescent mental health intervention, from which they identified 20 unique
      publications and 12 separate interventions. These interventions encompassed
      depression, anxiety, substance abuse, eating disorders, and mental health
      promotion. Studies were heterogeneous, with a wide range of study designs and
      comparison groups creating some challenges in interpretation. However, modest
      evidence was found that Internet interventions showed benefits compared with
      controls and preintervention symptom levels. Interventions had been developed for
      a range of settings, but tended to recruit middle-class participants of European
      ethnicity. Internet interventions showed a range of approaches toward engaging
      children and incorporating parents and peers into the learning process.

PMID- 21092921
TI  - I can't believe this isn't wood! An investigation in the perception of
      naturalness.
AB  - For most people "naturalness" is a highly appreciated material characteristic.
      For instance, a natural wooden floor is seen as more valuable than a fake
      replica, though they may be comparable in quality and durability. In the present
      study we investigated how sensory input (vision and touch) contributes to the
      perception of naturalness in wood. Participants rated samples of wood or
      imitations thereof, such as vinyl and veneers. We first attempted to provide a
      validation of the measurement of perceived naturalness by comparing four
      psychophysical measurement methods (labelled scaling, magnitude estimation,
      binary decision, and ranked ordering). Second, we investigated the contribution
      of vision and touch by measuring the perception of naturalness in three
      exploration modalities (vision only, touch only, and visuo-tactile). The results
      show a high degree of consistency across measurement methods, suggesting that we
      measured a common underlying construct that relates to naturalness. It also
      suggests that this construct is represented on a metathetic (categorical)
      continuum. Moreover, we found that both vision and touch are highly correlated
      predictors of visuo-tactile perception of naturalness.

PMID- 21092922
TI  - Pelizaeus-Merzbacher-like disease caused by AIMP1/p43 homozygous mutation.
AB  - Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused
      by PLP1 mutations. A similar autosomal-recessive phenotype, Pelizaeus-Merzbacher
      like disease (PMLD), has been shown to be caused by homozygous mutations in GJC2
      or HSPD1. We report a consanguineous Israeli Bedouin kindred with clinical and
      radiological findings compatible with PMLD in which linkage to PLP1, GJC2, and
      HSPD1 was excluded. Through genome-wide homozygosity mapping and mutation
      analysis, we demonstrated in all affected individuals a homozygous frameshift
      mutation that fully abrogates the main active domain of AIMP1, encoding ARS
      interacting multifunctional protein 1. The mutation fully segregates with the
      disease-associated phenotype and was not found in 250 Bedouin controls. Our
      findings are in line with the previously demonstrated inability of mutant mice
      lacking the AIMP1/p43 ortholog to maintain axon integrity in the central and
      peripheral neural system.

PMID- 21092923
TI  - Targeted next-generation sequencing of a 12.5 Mb homozygous region reveals ANO10
      mutations in patients with autosomal-recessive cerebellar ataxia.
AB  - Autosomal-recessive cerebellar ataxias comprise a clinically and genetically
      heterogeneous group of neurodegenerative disorders. In contrast to their dominant
      counterparts, unraveling the molecular background of these ataxias has proven to
      be more complicated and the currently known mutations provide incomplete coverage
      for genotyping of patients. By combining SNP array-based linkage analysis and
      targeted resequencing of relevant sequences in the linkage interval with the use
      of next-generation sequencing technology, we identified a mutation in a gene and
      have shown its association with autosomal-recessive cerebellar ataxia. In a Dutch
      consanguineous family with three affected siblings a homozygous 12.5 Mb region on
      chromosome 3 was targeted by array-based sequence capture. Prioritization of all
      detected sequence variants led to four candidate genes, one of which contained a
      variant with a high base pair conservation score (phyloP score: 5.26). This
      variant was a leucine-to-arginine substitution in the DUF 590 domain of a 16K
      transmembrane protein, a putative calcium-activated chloride channel encoded by
      anoctamin 10 (ANO10). The analysis of ANO10 by Sanger sequencing revealed three
      additional mutations: a homozygous mutation (c.1150_1151del [p.Leu384fs]) in a
      Serbian family and a compound-heterozygous splice-site mutation (c.1476+1G>T) and
      a frameshift mutation (c.1604del [p.Leu535X]) in a French family. This
      illustrates the power of using initial homozygosity mapping with next-generation
      sequencing technology to identify genes involved in autosomal-recessive diseases.
      Moreover, identifying a putative calcium-dependent chloride channel involved in
      cerebellar ataxia adds another pathway to the list of pathophysiological
      mechanisms that may cause cerebellar ataxia.

PMID- 21092925
TI  - Electrocardiogram for hiccups?

PMID- 21092924
TI  - Rare copy number variants disrupt genes regulating vascular smooth muscle cell
      adhesion and contractility in sporadic thoracic aortic aneurysms and dissections.
AB  - Thoracic aortic aneurysms and dissections (TAAD) cause significant morbidity and
      mortality, but the genetic origins of TAAD remain largely unknown. In a genome
      wide analysis of 418 sporadic TAAD cases, we identified 47 copy number variant
      (CNV) regions that were enriched in or unique to TAAD patients compared to
      population controls. Gene ontology, expression profiling, and network analysis
      showed that genes within TAAD CNVs regulate smooth muscle cell adhesion or
      contractility and interact with the smooth muscle-specific isoforms of alpha
      actin and beta-myosin, which are known to cause familial TAAD when altered.
      Enrichment of these gene functions in rare CNVs was replicated in independent
      cohorts with sporadic TAAD (STAAD, n = 387) and inherited TAAD (FTAAD, n = 88).
      The overall prevalence of rare CNVs (23%) was significantly increased in FTAAD
      compared with STAAD patients (Fisher's exact test, p = 0.03). Our findings
      suggest that rare CNVs disrupting smooth muscle adhesion or contraction
      contribute to both sporadic and familial disease.

PMID- 21092926
TI  - Iatrogenic glaucoma secondary to medications.
AB  - Glaucoma is a progressive optic neuropathy with primary and secondary forms.
      Iatrogenic glaucoma secondary to medications is potentially blinding but
      preventable. Most drug profiles listing glaucoma as a contraindication or an
      adverse effect are concerned with inducing acute angle-closure glaucoma.
      Anticholinergic or adrenergic agents are the most common for inducing "pupillary
      block" angle-closure glaucoma. Patients with a narrow irido-corneal angle are at
      high risk. Sulfa drugs induce "non-pupillary block" angle-closure glaucoma as an
      idiosyncratic reaction to the drug in patients with an open or narrow irido
      corneal angle. Steroids and a few antineoplastic agents induce open-angle
      glaucoma. The risk is higher with topical rather than systemic steroids. The
      first step in the management is discontinuation of the drug, followed by medical,
      laser, and, if necessary, surgical intervention.

PMID- 21092927
TI  - Pheochromocytoma presenting as fever of unknown origin.

PMID- 21092928
TI  - An uncommon cause of portal hypertension: schistosomiasis.

PMID- 21092929
TI  - Expression of epidermal growth factor receptor and vascular endothelial growth
      factor in vaginal squamous cell cancer.
AB  - OBJECTIVE: Primary invasive squamous cell carcinoma of the vagina is a rare
      neoplasm. Investigations concerning the potential of new therapeutic targets are
      limited. STUDY DESIGN: A total of 34 patients with primary invasive squamous cell
      carcinoma of the vagina was identified, who were treated at our institution
      between 1994 and 2008. Epidermal growth factor receptor (EGFR) and vascular
      endothelial growth factor (VEGF) expression was assessed using
      immunohistochemistry from paraffin-embedded tissue blocks. RESULTS: EGFR was
      expressed in 33 of 34 (97.1%) and VEGF was expressed in 12 of 34 cases (35.3%).
      There was no statistically significant relationship between clinicopathologic
      parameters (clinical stage, grading, tumor size), patient survival, and EGFR and
      VEGF expression. CONCLUSION: VEGF was moderate and EGFR was frequently expressed
      in invasive squamous cell carcinoma of the vagina. In our sample size,
      immunohistochemical staining was not statistically significantly associated with
      prognosis.

PMID- 21092930
TI  - Multiplexed analysis of circulating cell-free fetal nucleic acids for noninvasive
      prenatal diagnostic RHD testing.
AB  - OBJECTIVE: The objective of the study was the evaluation of a novel multiplex
      assay to detect fetal Rh blood group D-antigen gene (RHD) loci in maternal plasma
      from RhD-negative, pregnant women. STUDY DESIGN: An RHD genotyping assay was
      designed to detect exons 4, 5, 7, and 10 and RHDPsi (pseudogene) of the RHD gene
      along with a Y chromosome-specific assay and a generic polymerase chain reaction
      amplification control. Plasma samples from 150 RhD-negative pregnant women were
      assayed for fetal RHD genotype using the MassARRAY system. RESULTS: The fetal RHD
      status of 148 of 150 samples (98.7%) was correctly classified; 86 (57.3%) and 62
      (41.3%) were positive and negative, respectively. CONCLUSION: This study
      demonstrates that noninvasive prenatal diagnostics with a single-reaction
      multiplexed assay is a viable path toward routine characterization of fetal RHD
      genotypes using circulating cell-free fetal DNA in maternal plasma on the
      MassARRAY system and is perhaps preferable to serologic testing as currently used
      clinically.

PMID- 21092931
TI  - Use of visual force feedback to improve digit force direction during pinch grip
      in persons with stroke: a pilot study.
AB  - OBJECTIVE: To investigate whether visual feedback of digit force directions for
      the index fingertip and thumb tip during repeated practice of grip force
      production can correct the digit force directions for persons with stroke during
      grip assessments. Following stroke, the paretic fingers generate digit forces
      with a higher than normal proportion of shear force to compression force during
      grip. This misdirected digit force may lead to finger-object slip and failure to
      stably grasp an object. DESIGN: A case series. SETTING: Laboratory. PARTICIPANTS:
      Persons (N=11) with severe chronic hand impairment after stroke. INTERVENTIONS:
      Four training sessions during which participants practiced directing the index
      finger and thumb forces in various target directions during pinch using visual
      feedback. MAIN OUTCOME MEASURE: Digit force direction during pinch and clinical
      hand function scores were measured before and immediately after the training.
      RESULTS: Study participants were able to redirect the digit force closer to the
      direction perpendicular to the object surface and increase their hand function
      scores after training. The mean ratio of the shear force to the normal force
      decreased from 58% to 41% (SD, 17%), the mean Box and Block Test score increased
      from 1.4 to 3.4 (SD, 2.0), and the mean Action Research Arm Test score increased
      from 10.8 to 12.1 (SD, 1.3) (P<.05 for all 3 measures). CONCLUSIONS: Repeated
      practice of pinch with visual feedback of force direction improved grip force
      control in persons with stroke. Visual feedback of pinch forces may prove
      valuable as a rehabilitation paradigm for improving hand function.

PMID- 21092932
TI  - Exercises commonly used in rehabilitation of patients with chronic obstructive
      pulmonary disease: cardiopulmonary responses and effect over time.
AB  - OBJECTIVES: To compare conventional exercise-based assessment of pulmonary
      rehabilitation (PR) with improvement in training exercises employed during a PR
      program, and to describe the cardiopulmonary response of different training
      exercises during PR of patients with chronic obstructive pulmonary disease
      (COPD). DESIGN: Observational study. SETTING: Inpatient PR. PARTICIPANTS:
      Patients with moderate to very severe COPD (N=18). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Cardiopulmonary responses to interval cycling, arm
      exercise, and a test of functional activities of daily living (ADLs) were
      evaluated during the PR training program using a mobile telemetric breath-by
      breath system. The effects of PR were evaluated by comparing pre-PR and post-PR
      training activities, incremental and constant work-rate cycling, and a 6-minute
      walk test. RESULTS: Interval cycling and the ADLs test were moderate-intensity to
      heavy-intensity exercises (70%-80% of maximal oxygen consumption), while the arm
      exercise was a low-intensity activity (40% of maximal oxygen consumption). After
      12 weeks of PR, cycle load, arm weights, and walking distances during training
      activities had increased alongside increased muscle mass. At iso-intensities, no
      cardiopulmonary changes in the training exercises were observed. Exercise
      duration of constant work-rate cycling and 6-minute walk distance increased by
      160% and 14%, respectively, after PR, with concurrent right-shifts of anaerobic
      threshold and a decrease in heart rate. CONCLUSIONS: Supervised increases in
      weight, load, and walking distance during training activities were useful
      clinical outcomes for patients, demonstrating the beneficial effects of
      progressive training on physical performance. However, for physiologic evaluation
      of PR, conventional tests, such as maximal incremental cycling, endurance
      cycling, and a 6-minute walk test, had greater validity. Physiologic evaluation
      of the training exercises showed that the training program complied with the
      training recommendations for PR.

PMID- 21092933
TI  - Guided self-help for disordered eating: A randomised control trial.
AB  - Treatment guidelines recommend evidence-based guided self-help (GSH) as the first
      stage of treatment for bulimia nervosa and binge eating disorder. The current
      randomised control trial evaluated a cognitive behavioural therapy-based GSH
      pack, 'Working to Overcome Eating Difficulties,' delivered by trained mental
      health professionals in 6 sessions over 3 months. It was congruent with the
      transdiagnostic approach and so was intended as suitable for all disordered
      eating, except severe anorexia nervosa. Eighty one clients were randomly
      allocated to either a GSH or waiting list condition. Eating disorder
      psychopathology (EDE-Q), key behavioural features and global distress (CORE) were
      measured at pre- and post-intervention, and 3- and 6-month follow-up. Results
      showed significant improvements in eating disorder psychopathology, laxative
      abuse, exercise behaviours, and global distress, with the GSH condition being
      superior to the waiting list on all outcomes. Treatment gains were maintained at
      3 and 6 months. This study adds to the evidence supporting GSH for disordered
      eating, including EDNOS. However, further work is needed to establish the factors
      that contribute to observed therapeutic improvements and determine for whom GSH
      is most suitable.

PMID- 21092934
TI  - Long-term follow-up of internet-delivered exposure and mindfulness based
      treatment for irritable bowel syndrome.
AB  - We conducted a follow-up of a previously reported study of internet-delivered
      cognitive behavior therapy (CBT) for IBS, based on exposure and mindfulness
      exercises (Ljotsson et al. (2010). Internet-delivered exposure and mindfulness
      based therapy for irritable bowel syndrome - a randomized controlled trial.
      Behaviour Research and Therapy, 48, 531-539). Seventy-five participants from the
      original sample of 85 (88%) reported follow-up data at 15-18 months (mean 16.4
      months) after completing treatment. The follow-up sample included participants
      from both the original study's treatment group and waiting list after it had been
      crossed over to treatment. Intention-to-treat analysis showed that treatment
      gains were maintained on all outcome measures, including IBS symptoms, quality of
      life, and anxiety related to gastrointestinal symptoms, with mainly large effect
      sizes (within-group Cohen's d=0.78-1.11). A total of fifty participants (59% of
      the total original sample; 52% of the original treatment group participants and
      65% of the original waiting list participants) reported adequate relief of
      symptoms. Improvements at follow-up were more pronounced for the participants
      that had completed the full treatment and maintenance of improvement did not seem
      to be dependent on further treatment seeking. This study suggests that internet
      delivered CBT based on exposure and mindfulness has long-term beneficial effects
      for IBS-patients.

PMID- 21092935
TI  - Moving from efficacy to effectiveness trials in prevention research.
AB  - Efficacy trials test whether interventions work under optimal, highly controlled
      conditions whereas effectiveness trials test whether interventions work with
      typical clients and providers in real-world settings. Researchers, providers, and
      funding bodies have called for more effectiveness trials to understand whether
      interventions produce effects under ecologically valid conditions, which factors
      predict program effectiveness, and what strategies are needed to successfully
      implement programs in practice settings. The transition from efficacy to
      effectiveness with preventive interventions involves unique considerations, some
      of which are not shared by treatment research. The purpose of this article is to
      discuss conceptual and methodological issues that arise when making the
      transition from efficacy to effectiveness research in primary, secondary, and
      tertiary prevention, drawing on the experiences of two complimentary research
      groups as well as the existing literature. We address (a) program of research,
      (b) intervention design and conceptualization, (c) participant selection and
      characteristics, (d) providers, (e) context, (f) measurement and methodology, (g)
      outcomes, (h) cost, and (i) sustainability. We present examples of research in
      eating disorder prevention that demonstrate the progression from efficacy to
      effectiveness trials.

PMID- 21092936
TI  - Comparison of different strategies to decrease negative affect and increase
      positive affect in women with borderline personality disorder.
AB  - BACKGROUND: In this study we compared the effect of different emotion regulation
      strategies on positive and negative emotions in patients with borderline
      personality disorder. METHODS: Emotion regulation strategies were a distracting
      task, individual positive memory imagery, individual soothing imagery, and a
      neutral comparison condition. During two separate sessions, 17 participants
      watched either neutral or negative movie segments before using these strategies.
      RESULTS: All three strategies influenced emotions into a favorable direction as
      compared to the neutral comparison condition. The positive memory image increased
      positive emotions significantly stronger than counting colors and distracting.
      DISCUSSION: Different strategies seem to have similar effects in decreasing
      negative emotions. Positive emotions may be affected in particular by positive
      and soothing imagery techniques.

PMID- 21092937
TI  - Maternal depressive history, teen 5HTTLPR genotype, and the processing of
      emotional faces: Exploring mechanisms of risk.
AB  - Variations in the serotonin transporter gene (5HTTLPR) and biased processing of
      face-emotion displays both have been implicated in the transmission of depression
      risk, but little is known about developmental influences on these relationships.
      Within a community sample of adolescents, we examine whether 5HTTLPR genotype
      moderates the link between maternal depressive history and errors in face-emotion
      labeling. When controlling for current levels of depression and anxiety among
      youth, a two-way interaction between maternal depressive history and 5HTTLPR
      genotype was detected. Specifically, adolescents whose mothers reported a
      depressive history and who had a low expressing genotype made more errors in
      classifying emotional faces when compared with adolescents with an intermediate
      or high expressing genotype, with or without maternal depression history. These
      findings highlight the complex manner in which maternal depression and genetic
      risk may interact to predict individual differences in social information
      processing.

PMID- 21092940
TI  - Catalytic conversion of cellulose to chemicals in ionic liquid.
AB  - A simple and effective route for the production of 5-hydroxymethyl furfural (HMF)
      and furfural from microcrystalline cellulose (MCC) has been developed. CoSO(4) in
      an ionic liquid, 1-(4-sulfonic acid) butyl-3-methylimidazolium hydrogen sulfate
      (IL-1), was found to be an efficient catalyst for the hydrolysis of cellulose at
      150 degrees C, which led to 84% conversion of MCC after 300min reaction time. In
      the presence of a catalytic amount of CoSO(4), the yields of HMF and furfural
      were up to 24% and 17%, respectively; a small amount of levulinic acid (LA) and
      reducing sugars (8% and 4%, respectively) were also generated. Dimers of furan
      compounds were detected as the main by-products through HPLC-MS, and with the
      help of mass spectrometric analysis, the components of gas products were methane,
      ethane, CO, CO(2,) and H(2). A mechanism for the CoSO(4)-IL-1 hydrolysis system
      was proposed and IL-1 was recycled for the first time, which exhibited favorable
      catalytic activity over five repeated runs. This catalytic system may be valuable
      to facilitate energy-efficient and cost-effective conversion of biomass into
      biofuels and platform chemicals.

PMID- 21092939
TI  - Specific cognitive training normalizes auditory sensory gating in schizophrenia:
      a randomized trial.
AB  - BACKGROUND: The ratio of scalp-recorded brain responses occurring 50 msec after
      paired clicks (S2-evoked P50/S1-evoked P50) serves as a measure of sensory
      gating. An abnormally large ratio is commonly found in schizophrenia and is
      considered as a sign of reduced sensory gating or otherwise dysfunctional
      organization of the auditory/verbal system as a factor contributing to
      psychopathology and cognitive dysfunction in schizophrenia. This initial
      randomized clinical trial compared the efficacy of two 4-week, computer-based
      cognitive training methods that emphasize either auditory discrimination and
      verbal memory or a broader range of cognitive functions in schizophrenia.
      METHODS: Thirty-nine schizophrenia patients (ICD-F20.0 diagnosis) were assigned
      to Cognitive Exercises (CE) or Cognitive Package (Cogpack). The M50, the
      magnetoencephalographic analogue of electroencephalographic P50, and performance
      on verbal learning and memory tests were used to evaluate training effects.
      RESULTS: As expected, patients exhibited higher pretreatment gating ratios than
      28 age-matched healthy comparison participants. Gating ratios decreased after CE
      but not after Cogpack. Cognitive test performance improved more after CE than
      after Cogpack. CONCLUSIONS: Appropriately specific psychological training changes
      the neural performance in schizophrenia, normalizing sensory and cognitive
      function.

PMID- 21092938
TI  - Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric
      disorder.
AB  - BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic
      disorder that is characterized by affective symptoms, including irritability,
      depression, and anxiety, which arise in the luteal phase of the menstrual cycle
      and resolve soon after the onset of menses. Despite a prevalence of up to 8% in
      women of reproductive age, few studies have investigated the brain mechanisms
      that underlie this disorder. METHODS: We used positron emission tomography with
      [(18)F] fluorodeoxyglucose and self-report questionnaires to assess cerebral
      glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison
      subjects in the follicular and late luteal phases of the menstrual cycle. The
      primary biological end point was incorporated regional cerebral radioactivity
      (scaled to the global mean) as an index of glucose metabolism. Relationships
      between regional brain activity and mood ratings were assessed. Blood samples
      were taken before each session for assay of plasma estradiol and progesterone
      concentrations. RESULTS: There were no group differences in hormone levels in
      either the follicular or late luteal phase, but the groups differed in the effect
      of menstrual phase on cerebellar activity. Women with PMDD but not comparison
      subjects showed an increase in cerebellar activity (particularly in the right
      cerebellar vermis) from the follicular phase to the late luteal phase (p = .003).
      In the PMDD group, this increase in cerebellar activity was correlated with
      worsening of mood (p = .018). CONCLUSIONS: These findings suggest that the
      midline cerebellar nuclei, which have been implicated in other mood disorders,
      also contribute to negative mood in PMDD.

PMID- 21092941
TI  - Characterization of physical interaction between Casiopeina III-ia and chitosan.
      Toward a Cas III-ia drug delivery system.
AB  - Casiopeinas are a new generation of anticancer drugs that have shown great in
      vitro and in vivo antineoplastic activities. Information about interaction drug
      excipient, for developing a based-nanoparticle drug delivery system, has not been
      investigated yet. In order to elucidate if chitosan (CS) modifies the copper
      complex due to its interaction with Cu(2+) ion, different studies in aqueous
      media between CS and Casiopeina III-ia (Cas III-ia) were carried out. CS-Cas III
      ia mixtures were characterized by viscosity curves, UV-vis, EPR, and in vivo
      activity against HeLa cell line. Rheological behavior showed a decrease of
      viscosity when the drug was present due to diminished electrostatic interactions
      of charged amine group. UV-vis results illustrate that Cas III-ia is not stable
      at low pH as a result of interaction with acetic acid. However, when chitosan is
      present at the acidic solution Cas III-ia is stable. These results are supported
      by EPR studies. Finally, activity of the drug against HeLa cell line was not
      modified. Therefore, the present work presents evidence that there is no breaking
      of copper complex due to interaction between CS and Cas III-ia in acidic media.
      In addition, Cas III-ia maintains both its stability and effectiveness against
      cancer cell line.

PMID- 21092942
TI  - Lasting effects of an impairment of Th1-like immune response in gamma-irradiated
      mice: A resemblance between irradiated mice and aged mice.
AB  - Although one of the several chronic effects of ionizing radiation is aging, there
      are no experimental data on radiation-induced immunological aging. The most
      interesting change in aging was a helper T (Th) 1/Th2 imbalance. We investigated
      chronic effect on immune responses after ionizing radiation and its effects in
      irradiated mice were compared with those of aged mice. The 2-month-old mice
      received a whole-body irradiation of 5Gy. At 6months after irradiation, we
      compared the immune functions of the irradiated mice with those of normal mice of
      the same age and with those of older. Interferon (IFN)-gamma and antigen-specific
      immunoglobulin (Ig)G2a level were lower in the irradiated mice than in normal
      mice of same age, showing similar levels to those of old normal mice. In
      contrast, interleukin (IL)-4 and IL-5 and antigen-specific IgG1 level were
      increased in irradiated mice when compared with the same aged-normal mice. Next,
      we investigated the low expression of IL-12p70, IL-12 receptors and IL-18
      receptors in irradiated and old mice. Also, the decrease of natural killer cell
      activity was intensified in the irradiated mice, showing lower than values to
      those of old mice. Interestingly, in irradiated mice, the absolute numbers and
      the percentages of natural killer (NK) cells was extremely decreased. But the
      absolute numbers of Th cells and cytotoxic T (Tc) cells in old mice were
      significantly decreased. In conclusion, an immunological imbalance by the whole
      body irradiation of 5Gy induces to persist in the long term, resulting in the
      similar results with aging. Our results suggest that the downregulation of the
      Th1-like immune response shown in old mice rapidly occurred through exposure of
      ionizing radiation.

PMID- 21092943
TI  - Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo
      and in vitro.
AB  - Toll-like receptor 3 (TLR3) binds and signals in response to dsRNA and poly(I:C),
      a synthetic double stranded RNA analog. Activation of TLR3 triggers innate
      responses that may play a protective or detrimental role in viral infections or
      in immune-mediated inflammatory diseases through amplification of inflammation.
      Two monoclonal antibodies, CNTO4685 (rat anti-mouse TLR3) and CNTO5429 (CDRs from
      CNTO4685 grafted onto a mouse IgG1 scaffold) were generated and characterized.
      These mAbs bind the extracellular domain of mouse TLR3, inhibit poly(I:C)-induced
      activation of HEK293T cells transfected with mTLR3, and reduce poly(I:C)-induced
      production of CCL2 and CXCL10 by primary mouse embryonic fibroblasts. CNTO5429
      decreased serum IL-6 and TNFalpha levels post-intraperitoneal poly(I:C)
      administration, demonstrating in vivo activity. In summary, specific anti-mTLR3
      mAbs have been generated to assess TLR3 antagonism in mouse models of
      inflammation.

PMID- 21092944
TI  - Implicit semantic perception in object substitution masking.
AB  - Decades of research on visual perception has uncovered many phenomena, such as
      binocular rivalry, backward masking, and the attentional blink, that reflect
      'failures of consciousness'. Although stimuli do not reach awareness in these
      paradigms, there is evidence that they nevertheless undergo semantic processing.
      Object substitution masking (OSM), however, appears to be the exception to this
      rule. In OSM, a temporally-trailing four-dot mask interferes with target
      perception, even though it has different contours from and does not spatially
      overlap with the target. Previous research suggests that OSM has an early locus,
      blocking the extraction of semantic information. Here, we refute this claim,
      showing implicit semantic perception in OSM using a target-mask priming paradigm.
      We conclude that semantic information suppressed via OSM can nevertheless guide
      behavior.

PMID- 21092945
TI  - What's new? Children prefer novelty in referent selection.
AB  - Determining the referent of a novel name is a critical task for young language
      learners. The majority of studies on children's referent selection focus on
      manipulating the sources of information (linguistic, contextual and pragmatic)
      that children can use to solve the referent mapping problem. Here, we take a step
      back and explore how children's endogenous biases towards novelty and their own
      familiarity with novel objects influence their performance in such a task. We
      familiarized 2-year-old children with previously novel objects. Then, on novel
      name referent selection trials children were asked to select the referent from
      three novel objects: two previously seen and one completely novel object.
      Children demonstrated a clear bias to select the most novel object. A second
      experiment controls for pragmatic responding and replicates this finding. We
      conclude, therefore, that children's referent selection is biased by previous
      exposure and children's endogenous bias to novelty.

PMID- 21092946
TI  - Automatic detection of maximal oxygen uptake and ventilatory threshold.
AB  - Maximal oxygen uptake (VO(2max)) and ventilatory threshold (VT) are the most
      common measurements in exercise physiology laboratories for the objective
      characterization of the physiologic state of metabolic and respiratory systems.
      Several techniques for their identification were proposed in the literature: the
      aim of the present study was to review them and assess their performance when
      applied to experimental data. In the present study, the criteria to detect
      VO(2max) and VT from respiratory gas-exchange data were analysed and automatic
      procedures for the identification of these parameters were implemented. These
      procedures were then applied to experimental data in order to assess the
      verifiability, repeatability and sensitivity to measurement noise of each
      proposed method. The results suggest plateau- and RISE-105- as the most reliable
      automatic procedures for determining VO(2max), while respiratory exchange ratio-,
      ventilatory equivalent for O(2)- and P(ET,O2)-criteria appear to be the most
      reliable automatic procedures for estimating VT.

PMID- 21092947
TI  - Bias correction by use of errors-in-variables regression models in studies with K
      X-ray fluorescence bone lead measurements.
AB  - In-vivo measurement of bone lead by means of K-X-ray fluorescence (KXRF) is the
      preferred biological marker of chronic exposure to lead. Unfortunately,
      considerable measurement error associated with KXRF estimations can introduce
      bias in estimates of the effect of bone lead when this variable is included as
      the exposure in a regression model. Estimates of uncertainty reported by the KXRF
      instrument reflect the variance of the measurement error and, although they can
      be used to correct the measurement error bias, they are seldom used in
      epidemiological statistical analyzes. Errors-in-variables regression (EIV) allows
      for correction of bias caused by measurement error in predictor variables, based
      on the knowledge of the reliability of such variables. The authors propose a way
      to obtain reliability coefficients for bone lead measurements from uncertainty
      data reported by the KXRF instrument and compare, by the use of Monte Carlo
      simulations, results obtained using EIV regression models vs. those obtained by
      the standard procedures. Results of the simulations show that Ordinary Least
      Square (OLS) regression models provide severely biased estimates of effect, and
      that EIV provides nearly unbiased estimates. Although EIV effect estimates are
      more imprecise, their mean squared error is much smaller than that of OLS
      estimates. In conclusion, EIV is a better alternative than OLS to estimate the
      effect of bone lead when measured by KXRF.

PMID- 21092948
TI  - Traffic noise and hypertension.

PMID- 21092950
TI  - [Neoplasms diagnosed in internal medicine ward: determining characteristics and
      factors to define the diagnostic-therapeutic efforts].

PMID- 21092949
TI  - [Urinary tract infections in internal medicine].
AB  - OBJECTIVES: Analysis of characteristics of patients in internal medicine (IM)
      hospital wards in Spain with the diagnosis of urinary tract infection (UTI).
      PATIENTS AND METHODS: Observational, descriptive, retrospective study of a
      population of inpatients with UTI diagnosis (October-December, 2007). Recorded
      variables included personal data, risk factors for complicated UTI, diagnosis
      criteria, microbiological results and antibiotics used. RESULTS: A total of 992
      patients (61.8% women), from 57 hospitals, were recruited. Mean age was 75.3
      years old (SD 16.5), with 18.1% from nursing homes and with some physical
      dependence in 53.5%. The majority (78.3 %) had some risk factors (diabetes
      mellitus 33.6%, vesical catheterization 24.1%). Non-specific UTI was the most
      frequent diagnosis (38.1%). UTI was diagnosed in 46%, based exclusively on
      urinary sediment alterations and/or positive cultures. E. coli was the most
      frequent pathogen (64.17%), with intermediate sensitivity or resistance of 22.8%
      to amoxicillin-clavunanic, 34.8% to levofloxacin and 40.6% to ciprofloxacin.
      Amoxicillin-clavulanic was the most used antibiotic (30.9%). UTI delayed hospital
      discharge in a 13.3%. Intrahospital-UTI was statistically more frequent (23%)
      with vesical catheterization (50.5 vs 16.2%) and mortality (3.4%) in older
      patients (81.2 vs. 75.1 years old.), in patients with P. aeruginosa cultures
      (11.8 vs 4.1%) and in those with urinary sepsis (41.4 vs 16.2%). CONCLUSIONS:
      Patients in internal medicine wards with a UTI diagnosis are older and with risk
      factors. Frequently, UTI is diagnosed based on non-specific criteria. E. coli is
      the most frequent pathogen. Quinolones should not be the first-line treatment in
      complicated or severe UTI, due to the high percentages of resistance.

PMID- 21092951
TI  - Autoimmune progesterone dermatitis: clinical presentation and management with
      progesterone desensitization for successful in vitro fertilization.
AB  - OBJECTIVE: To report clinical cases of autoimmune progesterone (P) dermatitis,
      its relationship to IVF, and the potential for P desensitization to treat these
      cases to achieve viable pregnancies. DESIGN: Clinical description. SETTING:
      Institutional hospitalary practice. Allergy Division. PATIENT(S): Six patients
      from the Allergy Clinic consulting for cyclic rashes or anaphylaxis related to
      the luteal phase of the menstrual cycle. Three of the conditions were related to
      IVF. INTERVENTION(S): Skin tests were performed with P. For IVF, rapid 8- and 10
      step P desensitization protocols were performed, with increasing doses
      administered every 20 minutes via intravaginal suppositories. A rapid oral
      desensitization protocol was performed in one patient who required an oral
      contraceptive for uterine bleeding. MAIN OUTCOME MEASURE(S): Progesterone skin
      test results. Tolerance to P desensitization. Achievement of viable pregnancies.
      RESULT(S): Skin tests were positive in all patients and negative in 10 controls.
      Desensitization was successful in four patients: three patients for IVF,
      resulting in viable pregnancies. Another patient achieved tolerance to oral
      contraceptives. CONCLUSION(S): Women with autoimmune P dermatitis can be
      desensitized successfully to P. We provide the first evidence of successful P
      desensitization in patients requiring IVF culminating in successful pregnancies.

PMID- 21092952
TI  - Secondary intestinal lymphangiectasia due to multiple myeloma.

PMID- 21092953
TI  - Rupture of a pseudoaneurysm of the middle colic artery.

PMID- 21092954
TI  - Transoral endoscopic esophageal myotomy based on esophageal function testing in a
      survival porcine model.
AB  - BACKGROUND: The most effective treatment of achalasia is Heller myotomy.
      OBJECTIVE: To explore a submucosal endoscopic myotomy technique tailored on
      esophageal physiology testing and to compare it with the open technique. DESIGN:
      Prospective acute and survival comparative study in pigs (n = 12; 35 kg).
      SETTING: University animal research center. INTERVENTION: Eight acute-4 open and
      4 endoscopic-myotomies followed by 4 survival endoscopic procedures. MAIN OUTCOME
      MEASUREMENTS: Preoperative and postoperative manometry; esophagogastric junction
      (EGJ) distensibility before and after selective division of muscular fibers at
      the EGJ and after the myotomy was prolonged to a standard length by using the
      EndoFLIP Functional Lumen Imaging Probe (Crospon, Galway, Ireland). RESULTS: All
      procedures were successful, with no intraoperative and postoperative
      complications. In the survival group, the animals recovered promptly from
      surgery. Postoperative manometry demonstrated a 50% drop in mean lower esophageal
      sphincter pressure (LESp) in the endoscopic group (mean preoperative LESp, 22.2
      +/- 3.3 mm Hg; mean postoperative LESp, 11.34 +/- 2.7 mm Hg; P < .005) and a 69%
      loss in the open procedure group (mean preoperative LESp, 24.2 +/- 3.2 mm Hg;
      mean postoperative LESp, 7.4 +/- 4 mm Hg; P < .005). The EndoFLIP monitoring did
      not show any distensibility difference between the 2 techniques, with the main
      improvement occurring when the clasp circular fibers were taken. LIMITATIONS:
      Healthy animal model; small sample. CONCLUSION: Endoscopic submucosal esophageal
      myotomy is feasible and safe. The lack of a significant difference in EGJ
      distensibility between the open and endoscopic procedure is very appealing. Were
      it to be perfected in a human population, this endoscopic approach could suggest
      a new strategy in the treatment of selected achalasia patients.

PMID- 21092955
TI  - Swallowed fluticasone for the treatment of esophageal lichen planus.

PMID- 21092956
TI  - Stabilization of multi-input hybrid fractional-order systems with state delay.
AB  - In this paper, the stabilization of a particular class of multi-input linear
      systems of fractional order differential inclusions with state delay using
      variable structure control is considered. First, the sliding surface with a
      fractional order integral formula is defined, and then the sufficient conditions
      for stability of the sliding surface are derived. Also, the concepts related to
      sliding control stabilization of differential inclusion systems with integer
      order are extended to differential inclusion systems with fractional order 0<q<1.
      Furthermore, for stabilization of fractional order systems with delay in the
      state space, a feedback and the concept of the norm of a state space is
      exploited. Finally, simulation results are provided to show the effectiveness of
      the proposed method.

PMID- 21092957
TI  - Prevalence and genotype distribution of human papillomavirus in women with
      cervical cancer or high-grade precancerous lesions in Chengdu, western China.
AB  - OBJECTIVE: To study the prevalence and genotype distribution of human
      papillomavirus (HPV) among women with cervical cancer or high-grade squamous
      intraepithelial lesions (HSIL) in western China. METHODS: Cervical cast-off cells
      from 144 women with cervical cancer and 63 women with HSIL were tested for HPV
      genotypes using an oligonucleotide microarray. RESULTS: The overall HPV
      prevalence was 80.6% in cases of carcinoma and 61.9% in cases of HSIL. The most
      common genotypes were HPV-16 (carcinoma, 68.1%; HSIL, 34.9%) and HPV-58
      (carcinoma, 8.3%; HSIL, 17.5%). Other high-risk types included HPV-18, -31, -33, 
      35, -45, and -52, with HPV-18 more common in adenocarcinomas than in squamous
      cell carcinomas (21.4% vs 3.1%; P<0.02). The HPV prevalence was lower among
      patients older than 49 years (P<0.02). CONCLUSION: The prevalence of HPV-16 and
      HPV-58 was high. This finding may help to improve HPV vaccination and cervical
      cancer prevention programs in western China.

PMID- 21092958
TI  - A randomized clinical trial of a levonorgestrel-releasing intrauterine system and
      a low-dose combined oral contraceptive for fibroid-related menorrhagia.
AB  - OBJECTIVE: To compare the efficacy of a levonorgestrel-releasing intrauterine
      system (LNG-IUS) with that of a low-dose combined oral contraceptive (COC) in
      reducing fibroid-related menorrhagia. METHODS: In this single-center, open,
      randomized clinical trial, 58 women with menorrhagia who desired contraception
      were randomized to receive a LNG-IUS or COC. The outcomes included treatment
      failure, defined as the need for another treatment; menstrual blood loss (MBL) by
      the alkaline hematin method and a pictorial assessment chart (PBAC); hemoglobin
      levels; and "lost days." RESULTS: Treatment failed in 6 women (23.1%) in the LNG
      IUS group and 11 (37.9%) in the COC group, for a hazard ratio of 0.46 (95% CI,
      0.17-1.17, P=0.101). Using the alkaline hematin test, the reduction of MBL was
      significantly greater in the LNG-IUS group (90.9% +/- 12.8% vs 13.4% +/- 11.1%;
      P<0.001). Using PBAC scores, the reduction was also significantly greater in the
      LNG-IUS group (88.0% +/- 16.5% vs 53.5% +/- 5 1.2%; P=0.02). Moreover, hemoglobin
      levels increased from 9.7 +/- 1.9g/dL to 11.7 +/- 1.2g/dL (P<0.001) and lost days
      decreased from 8.2 +/- 3.3 days to 1.3 +/- 1.5 days (P=0.003) in the LNG-IUS
      group. CONCLUSION: Although the rate of treatment failure was similar in both
      groups, the LNG-IUS was more effective in reducing MBL than the COC in women with
      fibroid-related menorrhagia.

PMID- 21092961
TI  - Chemotaxis of mesenchymal stem cells within 3D biomimetic scaffolds--a modeling
      approach.
AB  - Bone tissue engineering is a promising strategy to repair local defects by
      implanting biodegradable scaffolds which undergo remodeling and are replaced
      completely by autologous bone tissue. Here, we consider a Keller-Segel model to
      describe the chemotaxis of bone marrow-derived mesenchymal stem cells (BMSCs)
      into a mineralized collagen scaffold. Following recent experimental results in
      bone healing, demonstrating that a sub-population of BMSCs can be guided into 3D
      scaffolds by gradients of signaling molecules such as SDF-1alpha, we consider a
      population of BMSCs on the surface of the pore structure of the scaffold and the
      chemoattractant SDF-1alpha within the pores. The resulting model is a coupled
      bulk/surface model which we reformulate following a diffuse-interface approach in
      which the geometry is implicitly described using a phase-field function. We
      explain how to obtain such an implicit representation and present numerical
      results on MUCT-data for real scaffolds, assuming a diffusion of SDF-1alpha being
      coupled to diffusion and chemotaxis of the cells towards SDF-1alpha. We observe a
      slowing-down of BMSC ingrowth after the scaffold becomes saturated with SDF
      1alpha, suggesting that a slow release of SDF-1alpha avoiding an early saturation
      is required to enable a complete colonization of the scaffold. The validation of
      our results is possible via SDF-1alpha release from injectable carrier materials,
      and an adaptation of our model to similar coupled bulk/surface problems such as
      remodeling processes seems attractive.

PMID- 21092960
TI  - Measurement of in vivo anterior cruciate ligament strain during dynamic jump
      landing.
AB  - Despite recent attention in the literature, anterior cruciate ligament (ACL)
      injury mechanisms are controversial and incidence rates remain high. One
      explanation is limited data on in vivo ACL strain during high-risk, dynamic
      movements. The objective of this study was to quantify ACL strain during jump
      landing. Marker-based motion analysis techniques were integrated with
      fluoroscopic and magnetic resonance (MR) imaging techniques to measure dynamic
      ACL strain non-invasively. First, eight subjects' knees were imaged using MR.
      From these images, the cortical bone and ACL attachment sites of the tibia and
      femur were outlined to create 3D models. Subjects underwent motion analysis while
      jump landing using reflective markers placed directly on the skin around the
      knee. Next, biplanar fluoroscopic images were taken with the markers in place so
      that the relative positions of each marker to the underlying bone could be
      quantified. Numerical optimization allowed jumping kinematics to be superimposed
      on the knee model, thus reproducing the dynamic in vivo joint motion. ACL length,
      knee flexion, and ground reaction force were measured. During jump landing,
      average ACL strain peaked 55+/-14 ms (mean and 95% confidence interval) prior to
      ground impact, when knee flexion angles were lowest. The peak ACL strain,
      measured relative to its length during MR imaging, was 12+/-7%. The observed
      trends were consistent with previously described neuromuscular patterns.
      Unrestricted by field of view or low sampling rate, this novel approach provides
      a means to measure kinematic patterns that elevate ACL strains and that provide
      new insights into ACL injury mechanisms.

PMID- 21092962
TI  - How high is a "high" Hirsch index in biomechanics research?

PMID- 21092964
TI  - Multiscale models of the hybrid palliation for hypoplastic left heart syndrome.
AB  - A less-invasive procedure that combines interventional stent placement in the
      ductus arteriosus and surgical banding of the branch pulmonary arteries has been
      recently introduced in the treatment of the hypoplastic left heart syndrome
      (HLHS). The hemodynamic behaviour of this hybrid approach has not been examined
      before in a mathematical model. In this study, a mathematical model of the hybrid
      procedure for HLHS is described, applying a multiscale approach that couples 3D
      models of the area of the surgical operation and lumped parameter models of the
      remaining circulation. The effects of various degrees of pulmonary banding and
      different stent sizes inserted in the ductus arteriosus on pulmonary-systemic
      flow ratio, cardiac output and oxygen delivery were assessed. Computational
      results suggest that balanced systemic and pulmonary blood flow and optimal
      systemic oxygen delivery are sensitive to the degree of pulmonary arterial
      banding and not to the size of the ductal stent.

PMID- 21092963
TI  - A simulation analysis of the combined effects of muscle strength and surgical
      tensioning on lateral pinch force following brachioradialis to flexor pollicis
      longus transfer.
AB  - Biomechanical simulations of tendon transfers performed following tetraplegia
      suggest that surgical tensioning influences clinical outcomes. However, previous
      studies have focused on the biomechanical properties of only the transferred
      muscle. We developed simulations of the tetraplegic upper limb following transfer
      of the brachioradialis (BR) to the flexor pollicis longus (FPL) to examine the
      influence of residual upper limb strength on predictions of post-operative
      transferred muscle function. Our simulations included the transfer, ECRB, ECRL,
      the three heads of the triceps, brachialis, and both heads of the biceps.
      Simulations were integrated with experimental data, including EMG and joint
      posture data collected from five individuals with tetraplegia and BR-FPL tendon
      transfers during maximal lateral pinch force exertions. Given a measured co
      activation pattern for the non-paralyzed muscles in the tetraplegic upper limb,
      we computed the highest activation for the transferred BR for which neither the
      elbow nor the wrist flexor moment was larger than the respective joint extensor
      moment. In this context, the effects of surgical tensioning were evaluated by
      comparing the resulting pinch force produced at different muscle strength levels,
      including patient-specific scaling. Our simulations suggest that extensor muscle
      weakness in the tetraplegic limb limits the potential to augment total pinch
      force through surgical tensioning. Incorporating patient-specific muscle volume,
      EMG activity, joint posture, and strength measurements generated simulation
      results that were comparable to experimental results. Our study suggests that
      scaling models to the population of interest facilitates accurate simulation of
      post-operative outcomes, and carries utility for guiding and developing
      rehabilitation training protocols.

PMID- 21092965
TI  - A biomechanical assessment to evaluate breed differences in normal porcine medial
      collateral ligaments.
AB  - Little information is available on the role of genetic factors and heredity in
      normal ligament behaviour and their ability to heal. Assessing these factors is
      challenging because of the lack of suitable animal models. Therefore, the purpose
      of this study was to develop a porcine model in order to evaluate and compare the
      biomechanical differences of normal medial collateral ligaments (MCLs) between
      Yorkshire (YK) and red Duroc (RD) breeds. It was hypothesized that biomechanical
      differences would not exist between normal YK and RD MCLs. Comparisons between
      porcine and human MCL were also made. A biomechanical testing apparatus and
      protocol specific to pig MCL were developed. Ligaments were subjected to cyclic
      and static creep tests and then elongated to failure. Pig MCL morphology,
      geometry, and low- and high-load mechanical behaviour were assessed. The custom
      designed apparatus and protocol were sufficiently sensitive to detect mechanical
      property differences between breeds as well as inter-leg differences. The results
      reveal that porcine MCL is comparable in both shape and size to human MCL and
      exhibits similar structural and material failure properties, thus making it a
      feasible model. Comparisons between RD and YK breeds revealed that age-matched RD
      pigs weigh more, have larger MCL cross-sectional area, and have lower MCL failure
      stress than YK pigs. The effect of weight may have influenced MCL geometrical and
      biomechanical properties, and consequently, the differences observed may be due
      to breed type and/or animal weight. In conclusion, the pig serves as a suitable
      large animal model for genetic-related connective tissue studies.

PMID- 21092966
TI  - Elucidation of extracellular matrix mechanics from muscle fibers and fiber
      bundles.
AB  - The importance of the extracellular matrix (ECM) in muscle is widely recognized,
      since ECM plays a central role in proper muscle development (Buck and Horwitz,
      1987), tissue structural support (Purslow, 2002), and transmission of mechanical
      signals between fibers and tendon (Huijing, 1999). Since substrate biomechanical
      properties have been shown to be critical in the biology of tissue development
      and remodeling (Engler et al., 2006; Gilbert et al., 2010), it is likely that
      mechanics are critical for ECM to perform its function. Unfortunately, there are
      almost no data available regarding skeletal muscle ECM viscoelastic properties.
      This is primarily due to the impossibility of isolating and testing muscle ECM.
      Therefore, this note presents a new method to quantify viscoelastic ECM modulus
      by combining tests of single muscle fibers and fiber bundles. Our results
      demonstrate that ECM is a highly nonlinearly elastic material, while muscle
      fibers are linearly elastic.

PMID- 21092967
TI  - Accuracy of single-plane fluoroscopy in determining relative position and
      orientation of total knee replacement components.
AB  - The accuracy of estimating the relative pose between knee replacement components,
      in terms of clinical motion, is important in the study of knee joint kinematics.
      The objective of this study was to determine the accuracy of the single-plane
      fluoroscopy method in calculating the relative pose between the femoral component
      and the tibial component, along knee motion axes, while the components were in
      motion relative to one another. The kinematics of total knee replacement
      components were determined in vitro using two simultaneous methods: single-plane
      fluoroscopic shape matching and an optoelectronic motion tracking system. The
      largest mean differences in relative pose between the two methods for any testing
      condition were 2.1 degrees , 0.3 degrees , and 1.1 degrees  in extension,
      abduction, and internal rotation respectively, and 1.3, 0.9, and 1.9 mm in
      anterior, distal, and lateral translations, respectively. For the optimized
      position of the components during dynamic trials, the limits of agreement,
      between which 95% of differences can be expected to fall, were -2.9 to 4.5
      degrees  in flexion, -0.9 to 1.5 degrees  in abduction, -2.4 to 2.1 degrees  in
      external rotation, -2.0 to 3.9 mm in anterior-posterior translation, -2.2 to
      0.4mm in distal-proximal translation and -7.2 to 8.6mm in medial-lateral
      translation. These mean accuracy values and limits of agreement can be used to
      determine whether the shape-matching approach using single-plane fluoroscopic
      images is sufficiently accurate for an intended motion tracking application.

PMID- 21092968
TI  - Optimization-based prediction of asymmetric human gait.
AB  - An optimization-based formulation and solution method are presented to predict
      asymmetric human gait for a large-scale skeletal model. Predictive dynamics
      approach is used in which both the joint angles and joint torques are treated as
      unknowns in the equations of motion. For the optimization formulation, the joint
      angle profiles are treated as the primary unknowns, and velocities and
      accelerations are calculated using them. In numerical implementation, the joint
      angle profiles are discretized using the B-spline interpolation. An algorithm is
      presented to inversely calculate the joint torques and the ground reaction
      forces. The sum of the joint-torques squared, called the dynamic effort, is
      minimized as the human performance measure. Constraints are imposed on the joint
      strengths (torques) and joint ranges of motion along with other physical
      constraints. The formulation is validated by simulating a symmetric gait and
      comparing the results with the experimental data. Then asymmetric gait motion is
      simulated, where the left and right step lengths are different. The kinematics
      and kinetics results from the simulation are presented and discussed. Predicted
      ground reaction forces are explained by using the inverted pendulum model.
      Predicted kinematics and kinetics have trends that are similar to those reported
      in the literature. Potential practical applications of the formulation and the
      solution approach are discussed.

PMID- 21092969
TI  - Wavelet decomposition of transmitted ultrasound wave through a 1-D muscle-bone
      system.
AB  - In the attempt for using ultrasound as a diagnostic device for osteoporosis,
      several authors have described the result of the in vitro experiment in which
      ultrasound is passed through a cancellous bone specimen placed in a water tank.
      However, in the in vivo setting, a patient's cancellous bone is surrounded by
      cortical and muscle layers. This paper considers in the one-dimensional case (1)
      what effect the cortical bone segments surrounding the cancellous segment would
      have on the received signal and (2) what the received signal would be when a
      source and receiver are placed on opposite sides of a structure consisting of a
      cancellous segment surrounded by cortical and muscle layers. Mathematically this
      is accomplished by representing the received signal as a sum of wavelets which go
      through different reflection-transmission histories at the muscle-cortical bone
      and cortical-cancellous bone interfaces. The muscle and cortical bone are modeled
      as elastic materials and the cancellous bone as a poroelastic material described
      by the Biot-Johnson-Koplik-Dashen model. The approach presented here permits the
      assessment of which possible paths of transmission and reflection through the
      cortical-cancellous or muscle-cortical-cancellous complex will result in
      significant contributions to the received waveform. This piece of information can
      be useful for solving the inverse problem of non-destructive assessment of
      material properties of bone. Our methodology can be generalized to three
      dimensional parallelly layered structure by first applying Fourier transform in
      the directions perpendicular to the transverse direction.

PMID- 21092970
TI  - Influences of spherical tip radius, contact depth, and contact area on
      nanoindentation properties of bone.
AB  - Nanoindentation has been widely used as a means to measure the micro-mechanical
      properties of bone and to predict the macroscopic properties. The role of indent
      depth and indenter tip geometry in measuring the hierarchical properties of bone
      tissue was explored experimentally using a range of spherical indenter tips of
      R=5, 25, 65, and 200 MUm. Nanoindentation arrays, not targeted to fall on
      specific structures or locations, enabled statistical sampling of osteons within
      PMMA-embedded, bovine, cortical bone on a single sample to a range of maximum
      displacements (minimum of 100 nm and maximum of 2000 nm). Elastic finite element
      models were then utilized to isolate the contributions of indenter tip radius,
      contact area, and position within the lamellar structure in comparison to the
      experimental results. For a small, R=5 MUm indenter tip, indentation modulus
      consistently increased with contact depth and increased plastic deformation,
      resulting in an artificial increase in elastic properties. While larger radius
      tips (R=25, 65, and 200 MUm) did not enable evaluation of a high spatial
      resolution on the surface, they produced data that was representative of the
      lower load and contact depth measurements with the smaller tip. However the
      sensitivity to mechanical property variations across the 2-D surface of the
      material was lost with increase in indenter tip size. Correspondingly,
      measurement variance was also decreased as the volume contributing to the indent
      response represented an average of surface roughness, varying mineral content,
      defects, and underlying tissue type and structure.

PMID- 21092971
TI  - Epimerization and hydrolysis of 3,6-dimethyl-2,3,5,6
      tetrahydro[1,2,4]thiadiazino[6,5,4-hi]indole 1,1-dioxide.
AB  - In this study, configurational and chemical stability of (R,R),(S,S),(R,S),(S,R)
      3,6-dimethyl-2,3,5,6-tetrahydro[1,2,4]thiadiazino[6,5,4-hi]indole 1,1-dioxide (1)
      were investigated by dynamic and stopped-flow HPLC methods. Single epimeric
      mixtures (R,R),(R,S)-1 and (S,S),(S,R)-1 were obtained combining synthetic and
      chromatographic strategies. Separation of (R,R)-1 and (R,S)-1 was achieved by
      chiral chromatography and absolute configuration of eluted epimers has been
      assigned basing on molecular modelling calculations. Epimerization and hydrolysis
      of (R,R),(R,S)-1 have been studied by classical off-column, dynamic HPLC and
      stopped-flow HPLC methods. The influence of different parameters, such as
      temperature, pH and dielectric constant was evaluated. The data obtained indicate
      that (R,R),(R,S)-1 undergoes to a rapid epimerization in aqueous solvent and
      hydrolysis in acidic conditions. Moreover, epimerization and hydrolysis were
      investigated in presence of an artificial membrane and in physiological buffers
      (pH 2.2 and 7.0 at 37.5 degrees C) to simulate in vivo conditions.

PMID- 21092972
TI  - Editorial on "Current approaches to trace analysis of pharmaceuticals and
      personal care products in the environment", by Wolfgang Buchberger.

PMID- 21092974
TI  - Comprehensive two-dimensional gas chromatography for the analysis of Fischer
      Tropsch oil products.
AB  - The Fischer-Tropsch (FT) process involves a series of catalysed reactions of
      carbon monoxide and hydrogen, originating from coal, natural gas or biomass,
      leading to a variety of synthetic chemicals and fuels. The benefits of
      comprehensive two-dimensional gas chromatography (GC*GC) compared to one
      dimensional GC (1D-GC) for the detailed investigation of the oil products of low
      and high temperature FT processes are presented. GC*GC provides more accurate
      quantitative data to construct Anderson-Schultz-Flory (ASF) selectivity models
      that correlate the FT product distribution with reaction variables. On the other
      hand, the high peak capacity and sensitivity of GC*GC allow the detailed study of
      components present at trace level. Analyses of the aromatic and oxygenated
      fractions of a high temperature FT (HT-FT) process are presented. GC*GC data have
      been used to optimise or tune the HT-FT process by using a lab-scale micro-FT
      reactor.

PMID- 21092973
TI  - Hypercrosslinking: new approach to porous polymer monolithic capillary columns
      with large surface area for the highly efficient separation of small molecules.
AB  - Monolithic polymers with an unprecedented surface area of over 600 m(2)/g have
      been prepared from a poly(styrene-co-vinylbenzyl chloride-co-divinylbenzene)
      precursor monolith that was swollen in 1,2-dichloroethane and hypercrosslinked
      via Friedel-Crafts reaction catalyzed by ferric chloride. Both the composition of
      the reaction mixture used for the preparation of the precursor monolith and the
      conditions of the hypercrosslinking reaction have been varied using mathematical
      design of experiments and the optimized system validated. Hypercrosslinked
      monolithic capillary columns contain an array of small pores that make the column
      ideally suited for the high efficiency isocratic separations of small molecules
      such as uracil and alkylbenzenes with column efficiencies reproducibly exceeding
      80,000 plates/m for retained compounds. The separation process could be
      accelerated while also improving peak shape through the use of higher
      temperatures and a ternary mobile phase consisting of acetonitrile,
      tetrahydrofuran, and water. As a result, seven compounds were well separated in
      less than 2 min. These columns also facilitate separations of peptide mixtures
      such as a tryptic digest of cytochrome c using a gradient elution mode which
      affords a sequence coverage of 93%. A 65 cm long hypercrosslinked capillary
      column used in size exclusion mode with tetrahydrofuran as the mobile phase
      afforded almost baseline separation of toluene and five polystyrene standards.

PMID- 21092975
TI  - Martin-Synge algorithm for the solution of equilibrium-dispersive model of liquid
      chromatography.
AB  - An alternative method, called the Martin-Synge algorithm, is introduced to
      calculate numerical solutions of the equilibrium-dispersive (ED) model. The
      developed algorithm is based on the earlier work of Friday and Levan and on the
      continuous plate model of Martin and Synge. The column is divided evenly into a
      series of virtual vessels in which a simplified mass balance equation is solved
      accurately by the Runge-Kutta-Fehlberg method and the elution profile is given by
      the numerical solution for the last vessel. The dispersion of the compound during
      the elution process is controlled by adjusting the number of virtual vessels into
      which the column is divided. Solving the ED model under linear conditions with
      this method gives exactly the same profile as the analytical solution of the
      Martin-Synge plate model. The Martin-Synge method gives better results than the
      Rouchon method (1) when the isotherms involved are sigmoidal or anti-Langmuir;
      and, more importantly, (2) in the case of multi-component problems. Finally, the
      Martin-Synge method proves to be more robust and faster than the OCFE method
      that, until now, was considered to be one of the most robust and accurate
      algorithms. The developed algorithm was used for the calculation of the
      coefficients of the isotherm of butyl benzoate by the inverse method, using a
      simplex optimization algorithm.

PMID- 21092976
TI  - Preparative isolation of novel antioxidant flavonoids of alfalfa by stop-and-go
      counter-current chromatography and following on-line liquid chromatography
      desalination.
AB  - In this work, we have established a new stop-and-go two-dimensional
      chromatography coupling of counter-current chromatography and liquid
      chromatography (2D CCC * LC) for the preparative separation of two novel
      antioxidant flavonoids from the extract of alfalfa (Medicago sativa L.). The CCC
      column has been used as the first dimension to purify the target flavonoids using
      a solvent system of isopropanol and 20% sodium chloride aqueous solution (1:1,
      v/v) with the stop-and-go flow technique, and the LC column packed with
      macroporous resin has been employed as the second dimension for on-line
      absorption, desalination and desorption of the targeting effluents purified from
      the first CCC dimension. As a result, two novel flavonoids, 6,8-dihydroxy-flavone
      7-O-beta-D-glucuronide (15.3 mg) and 6-methoxy-8-hydroxy-flavone-7-O-beta-D
      glucuronide (13.7 mg), have been isolated from 126.8 mg of crude sample pre
      enriched by macroporous resin column. Their structures have been identified by
      electrospray ionization mass spectrometry (ESI-MS), electrospray ionization time
      of-flight mass spectrometry (ESI-TOF-MS) and one- and two-dimensional nuclear
      magnetic resonance spectra (1D and 2D NMR). Further antioxidant assays showed
      that the first component possess a strong antioxidant activity. All the results
      demonstrated that the stop-and-go 2D CCC * LC method is very efficient for the
      separation of flavonoids of alfalfa and it can also be applied to isolate other
      comprehensive multi-component natural products.

PMID- 21092977
TI  - Theoretical optimisation of the side-wall of micropillar array columns using
      computational fluid dynamics.
AB  - The present study provides an overview of the ideal side-wall position in micro
      pillar array columns for the case of semi-embedded side-walls. The position has
      been determined using computational fluid dynamics simulations of the flow field
      in flow domains with different side-wall shifts. Optimal side-wall shift values
      are presented for a wide range of shapes (cylinders, and diamonds and hexagons
      with different aspect ratios) and packing densities. Simple linear correlations
      that allow calculating the optimised side-wall geometries for the different
      considered variety of shapes and packing densities could be established.
      Interestingly, only two correlations are needed to represent all investigated
      cases: one correlation for all diamonds, and one correlation for the cylinders
      and all hexagons. Compared to the case of a flat side-wall, the minimal feature
      size on the mask can be increased by a factor of 2.5 in the case of cylindrical
      pillar bed with external porosity E=0.4, implying that that much smaller pillar
      diameters can be used in the bulk of the bed before the minimal feature size on
      the mask falls below the lithography resolution.

PMID- 21092978
TI  - Optimization of large volume injection-programmable temperature vaporization-gas
      chromatography-mass spectrometry analysis for the determination of estrogenic
      compounds in environmental samples.
AB  - Large volume injection-programmable temperature vaporization-gas chromatography
      mass spectrometry (LVI-PTV-GC-MS) was optimized for the determination of estrone
      (E1), 17beta-estradiol (E2), 17alpha-ethynyl estradiol (EE2), mestranol (MeEE2)
      and estriol (E3) for their determination in environmental samples (estuarine
      water, wastewater, fish bile and fish homogenate) after derivatization with 25
      MUL (BSTFA+1% TMCS) and 125 MUL of pyridine. Experimental designs such as
      Plackett-Burman (PBD) and central composite designs (CCDs) were used to optimize
      the LVI-PTV variables (cryo-focusing temperature, vent time, vent flow, vent
      pressure, injection volume, purge flow to split vent, splitless time and
      injection speed). Optimized conditions were as follows: 45 MUL of n-hexane
      extract are injected at 60 degrees C and 6 MUL/s with a vent flow and a vent
      pressure of 50 mL/min and 7.7 psi, respectively, during 5 min; then the split
      valve is closed for 1.5 min and afterwards the injector is cleaned at 100 mL/min
      before the next injection. The method was applied to the determination of
      estrogenic compounds in environmental samples such as estuarine water,
      wastewater, and fish homogenate and bile. Limits of detection (0.04-0.15 ng/L for
      water samples, 0.04-0.67 ng/g for fish bile and 0.1-7.5 ng for fish homogenate)
      obtained were approx. ten times lower than those obtained by means of a common
      split/splitless inlet.

PMID- 21092979
TI  - In(2)O(3) microbundles constructed with well-aligned single-crystalline nanorods:
      F127-directed self-assembly and enhanced gas sensing performance.
AB  - Hierarchical In(2)O(3) rod-like microbundles were fabricated via the Pluronic
      F127-(EO(106)PO(70)EO(106)-) assisted hydrothermal reaction followed by calcining
      the In(OH)(3) precursors. The results revealed that the In(2)O(3)
      microarchitectures were constructed with well-aligned one-dimensional (1D) single
      crystalline nanorods with highly uniform morphologies and particular exposed
      facets. Structural analysis suggested that the In(2)O(3) nanorods were enclosed
      by {110} and {001} facets. The triblock copolymer acted as a structure-directing
      agent and played a key role in the formation of In(OH)(3) microbundles. The
      formation of the precursors In(OH)(3) microbundles was studied through
      contrastive experiments and computational simulation, which can be contributed to
      the soft-template-directed self-assembly mechanism. The gas sensing properties of
      the as-prepared In(2)O(3) microbundles were investigated. Compared to the samples
      prepared in the absence of F127, the In(2)O(3) microbundles exhibited a superior
      sensing performance toward 2-chloroethanol vapor, which can be explained by
      hierarchically ordered structures and exposed crystal surfaces.

PMID- 21092980
TI  - Deagglomeration and surface modification of thermally annealed nanoscale diamond.
AB  - Thermally annealed nanodiamond has been functionalized by C-C coupling of the
      partially graphitized diamond surface using aryl diazonium salts. Depending on
      the terminal functional groups, the modified bucky diamond nanoparticles show
      good solubility (up to 0.63mgmL(-1)) in different solvents. The agglomerate size
      of the originally strongly bound detonation diamond (>0.5MUm) is substantially
      reduced to ~20-50nm by this chemical procedure and without using mechanical
      techniques such as strong ultrasound or milling. Arylation with functionalized
      aryl diazonium salts carrying COOH, SO(3)H, NO(2) or bromoethyl groups opens the
      way for further covalent grafting of organic structures. Arylation with Ar-COOH
      or Ar-SO(3)H leads to the formation of stable colloidal solutions in water and
      physiological media (i.e. PBS buffer), an important prerequisite for biomedical
      applications.

PMID- 21092981
TI  - Perception and production of object-related grasping in 6-month-olds.
AB  - In this study, 6-month-olds' perception of an object-related human grasping
      action was compared with their level of grasping performance using a within
      participants design. In the action perception task, infants were presented with
      the video of an actor's grasping movement toward an occluded target object.
      Subsequently, an expected and an unexpected final state of this grasping movement
      were presented simultaneously, and infants' looking times were measured. In the
      action production task, infants were presented with three graspable objects.
      Infants' grasping behavior was coded to be either palmar or thumb-opposite
      grasping. Results indicate that infants who were already able to perform a thumb
      opposite grasp differentiated between the two final states in the action
      perception task by looking longer toward the unexpected final state. In contrast,
      infants who showed only palmar grasps looked equally long toward both final
      states. This finding supports the assumption that action perception and action
      control are already closely related in infants as young as 6 months.

PMID- 21092983
TI  - Task switching and shifting between stopping and going: Developmental change in
      between-trial control adjustments.
AB  - This study set out to investigate developmental differences in the ability to
      switch between choice tasks and to shift between Go/NoGo and choice tasks. Three
      age groups (7-year-olds, 11-year-olds, and young adults) were asked to consider
      the shape or color of a bivalued target stimulus. The participants performed a
      switch task in which a cue signaled the task to be performed (i.e., respond to
      shape vs. respond to color) and a shift task in which a cue instructed them to
      make a choice reaction to the shape of the stimulus or to respond (Go) versus
      inhibit (NoGo) to the color of the stimulus. The ability to switch was examined
      by considering choice-choice switches versus choice-choice repeats. The ability
      to shift was examined by considering NoGo-to-choice shifts versus choice-choice
      repeats and NoGo-to-Go shifts versus Go-Go repeats. The results showed that
      responding on Go trials was delayed following response inhibition on a NoGo
      trial. This delay did not discriminate between age groups. Responding on choice
      trials was considerably slowed when following response inhibition on NoGo trials.
      This slowing decreased with advancing age. Finally, responses on switch trials
      were slower compared with repeat trials, and this slowing was disproportionately
      large in young children compared with the other two age groups. This pattern of
      findings was interpreted in terms of a generic mechanism involving between-trial
      control adjustments in the setting of response thresholds that are likely to be
      mediated by a complex neural network implicating the dorsolateral prefrontal
      cortex and the presupplementary motor cortex.

PMID- 21092982
TI  - Thinking about representations: the case of opaque contexts.
AB  - To address the question of whether young children are differentially sensitive to
      referential opacity, an advanced Theory of Mind skill, we assessed 4-, 6-, and 8
      year-olds on three types of opaque contexts: epistemic, quotational, and
      intentional. Children's performance improved as a function of age and varied
      significantly by opacity type. Performance was best for epistemic opacity (using
      the verb "know") and poorest for intentional opacity (using "mean to"), with
      quotational opacity (using "said") falling in-between. Importantly, the current
      results suggest that children's sensitivity to referential opacity is not an all
      or-nothing competence but rather one that varies across the contexts examined.
      Possible reasons for this variability are discussed.

PMID- 21092984
TI  - Counterfactual thinking and false belief: the role of executive function.
AB  - The purpose of the current study was to examine further the relationship between
      counterfactual thinking and false belief (FB) as examined by Guajardo and Turley
      Ames (Cognitive Development, 19 (2004) 53-80). More specifically, the current
      research examined the importance of working memory and inhibitory control in
      understanding the relationship between counterfactual thinking and FB.
      Participants were 3-, 4-, and 5-year-olds (N=76). Counterfactual thinking
      statements generated accounted for significant variance in FB performance beyond
      age and language. Working memory and inhibitory control each partially mediated
      the relationship between counterfactual thinking and FB performance. The
      maturation of executive functioning skills is important in children's developing
      understanding of counterfactual reasoning and FB.

PMID- 21092985
TI  - Smoking and ADHD: an evaluation of self medication and behavioral disinhibition
      models based on comorbidity and personality patterns.
AB  - OBJECTIVE: The prevalence of smoking is significantly increased among adults with
      Attention-Deficit/Hyperactivity Disorder (ADHD), and this association has a
      significant impact in both disorders, ascribed to either self-medication or
      behavioral disinhibition hypotheses. However, little is known about clinical
      variables associated with cigarette smoking among patients with ADHD. The present
      study evaluates comorbidity, demographic and personality profiles of patients
      with ADHD in relation to smoking status. METHODS: Patients (n422) were evaluated
      in the adult ADHD outpatient clinic of Hospital de Clinicas de Porto Alegre.
      Diagnoses were based on DSM-IV criteria and interviews were performed with
      Portuguese version of K-SADS-E for ADHD and Oppositional-Defiant Disorder. Axis I
      psychiatric comorbidities were evaluated with the SCID-I and smoking behavior
      with Fagerstrom Test for Nicotine Dependence (FTND). Personality was evaluated
      with Cloninger's Temperament and Character Inventory (TCI). RESULTS: The presence
      of smoking was strongly associated with externalizing characteristics as
      antisocial personality disorder (OR4.2) and substance dependence (OR6.5), but not
      with internalizing disorders. Moreover, smoking was associated with higher
      novelty seeking and lower harm avoidance scores. CONCLUSIONS: Smoking initiation
      among patients with ADHD is consistent with a behavioral disinhibition profile
      beyond the possible role of self-medication in smoking persistence. Smoking in
      these patients is strongly associated with externalizing comorbid disorders.

PMID- 21092986
TI  - Clarifying the role of emotion dysregulation in the interpersonal-psychological
      theory of suicidal behavior in an undergraduate sample.
AB  - The interpersonal-psychological theory of suicidal behavior (IPTS; Joiner, 2005)
      has been subjected to a number of rigorous investigations and has shown to be a
      promising lens through which to understand suicide. One area thus far left
      unstudied with respect to the IPTS is emotion dysregulation. The bulk of the work
      examining the role of emotion dysregulation in suicidality has focused on
      suicidal ideation rather than behavior, with a number of studies reporting that
      emotion dysregulation is predictive of suicidal ideation (e.g., Lynch et al.,
      2004; Orbach et al., 2007). Studies examining suicide attempts have produced more
      ambiguous results. One way to clarify the nature of this relationship is to
      consider the construct of emotion dysregulation through an examination of
      specific subcomponents. In this study, we examined two specific components of
      emotion dysregulation - negative urgency and distress tolerance - and their
      relationships to all three components of the IPTS, thereby providing clarity for
      an otherwise poorly understood relationship. Results indicated that emotionally
      dysregulated individuals - those with low distress tolerance and high negative
      urgency - exhibited higher levels of suicidal desire, as indexed by perceived
      burdensomeness and thwarted belongingness. In contrast, emotionally dysregulated
      individuals exhibited lower levels of the acquired capability for suicide and
      physiological pain tolerance. As such, a complicated but theoretically cogent
      picture emerged indicating that, although emotion dysregulation may drastically
      increase the likelihood of suicidal desire, it simultaneously serves as a form
      protection against lethal self-harm.

PMID- 21092987
TI  - Cortical thickness is associated with poor insight in first-episode psychosis.
AB  - Through conceptualizing poor insight in psychotic disorders as a form of
      anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a
      vital role in its pathogenesis. Whether non-frontal brain regions are important
      for insight remains to be investigated. We used a multi-method approach to
      examine the neural morphometry of all cortical regions for insight in first
      episode psychosis. Insight was rated in 79 people with a first-episode psychosis
      with the awareness of illness and awareness of treatment need and efficacy items
      of the Scale for assessment of Unawareness of Mental Disorder. Participants were
      assessed with magnetic resonance imaging. Cortical thickness analysis and voxel
      based morphometry were utilized to identify the possible neuroanatomical basis of
      insight. Cortical thickness technique revealed that poorer awareness of illness
      was associated with regional thinning in left middle frontal and inferior
      temporal gyri. Poorer awareness of treatment need and efficacy was associated
      with cortical thinning in left medial frontal gyrus, precuneus and temporal gyri.
      No significant associations emerged between any insight measure and gray matter
      density using voxel-based morphometry. The results confirm predictions derived
      from the anosognosia/neuropsychology account and assert that regional thickness
      in frontal cortex is associated with awareness of illness in the early phase of
      psychosis. The fact that prominent thickness reductions emerged in non-frontal
      regions of the brain in parietal and temporal cortices for both awareness of
      illness and awareness of treatment need and efficacy suggests that the neural
      signature of insight involves a network of brain structures, and not only the
      frontal lobes as previously suggested.

PMID- 21092988
TI  - Effects of lazaroids on intestinal ischemia and reperfusion injury in
      experimental models.
AB  - Mesenteric ischemia occurs in a number of clinically relevant pathophysiologic
      processes, including sepsis, hemorrhage, intestinal transplantation, severe
      burns, and mesenteric thrombosis. The readmission of molecular oxygen into an
      ischemic tissue promotes the oxidation of resuscitated tissue with certain
      pathophysiologic mechanisms. Depending on the duration and the intensity of
      ischemia, reoxygenation of the intestine that has been reperfused may further
      induce tissue injury. Intestinal ischemia and reperfusion injury can accelerate
      complex processes between the endothelium and different cell types leading to
      microvascular injury, cellular necrosis, and apoptosis. The injury due to
      reperfusion is found predominantly in the intestinal mucosa and submucosa,
      causing endothelial detachment. The 21-aminosteroids (lazaroids) are a family of
      compounds that inhibit lipid membrane peroxidation. Many of the performed studies
      show conflicting results, which reflect differences in experimental design,
      evolving time that (I/R) is induced, total or partial vascular occlusion, dosage
      of the lazaroid, and the exact period of time that the lazaroid is administered.

PMID- 21092989
TI  - Transapical aortic valve implantation after previous aortic valve replacement:
      clinical proof of the "valve-in-valve" concept.
AB  - OBJECTIVE: The "valve-in-valve" concept may be applied in patients with
      previously implanted biological aortic valve prostheses. There are few reports of
      individual cases and as yet no clinical proof of safety and feasibility in a
      larger group of patients. We report the single-center outcome of transapical
      implantation of aortic valves into degenerated biological aortic valve prostheses
      ("valve-in-valve") in very high-risk patients. METHODS: Since October 2008, 14
      patients were treated by transapical valve implantation into degenerated
      biological aortic valve prostheses. Edwards SAPIEN (Edwards Lifesciences, Irvine,
      Calif) transcatheter heart valves were used in all patients. Mean (+/- standard
      deviation) patient age was 73.3 +/- 13.1 years. Mean (+/- standard deviation)
      Society of Thoracic Surgeons score was 21.9% +/- 10.9% (range, 4.2%-42.2%), and
      logistic euroSCORE was 45.3% +/- 22.2%. Preoperatively, all patients were in New
      York Heart Association functional class III or IV. RESULTS: The procedural
      success was 100%. Preoperative transthoracic echocardiography mean transvalvular
      gradient was reduced from 37.1 +/- 25.7 mm Hg to 13.1 +/- 6.4 mm Hg, and mean
      aortic valve area increased from 0.68 +/- 0.23 cm(2) to 1.35 +/- 0.48 cm(2).
      There was no postoperative valve insufficiency. The postoperative course was
      short and uneventful in all but 1 patient. One patient underwent reoperation 3
      months later because of endocarditis. Up to 20 months postoperatively, the
      patients were in New York Heart Association functional class I or II.
      CONCLUSIONS: Transapical aortic valve implantation after previous aortic valve
      replacement was feasible and safe in our patients. The results are excellent with
      improvements in hemodynamics, but longer follow-up with more patients is needed.

PMID- 21092990
TI  - Survival of patients with clinical stage IIIA non-small cell lung cancer after
      induction therapy: age, mediastinal downstaging, and extent of pulmonary
      resection as independent predictors.
AB  - BACKGROUND: In clinical stage IIIA non-small cell lung cancer, the role of
      surgical resection, particularly pneumonectomy, after induction therapy remains
      controversial. Our objective was to determine factors predictive of survival
      after postinduction surgical resection. METHODS: We retrospectively reviewed a
      prospectively collected database of 136 patients who underwent surgical resection
      after induction chemotherapy (n = 119) or chemoradiation (n = 17) from June 1990
      to January 2010. RESULTS: One hundred five lobectomies or bilobectomies and 31
      pneumonectomies were performed. There was 1 perioperative death (pneumonectomy).
      Seventy-one patients had downstaging to N0 or N1 nodal status (52%). There were 2
      complete pathologic responses. Median follow-up was 42 months (range, 0.69-136
      months). Overall 5-year survival for entire cohort was 33% (36% lobectomy, 22%
      pneumonectomy, P = .001). Patients with pathologic downstaging to pN0 or pN1 had
      improved 5-year survival (45% vs 20%, P = .003). For patients with pN0 or pN1
      disease, survival after lobectomy was better than after pneumonectomy (48% vs
      27%, P = .011). In patients with residual N2 disease, there was no statistically
      significant survival difference between lobectomy and pneumonectomy (5-year
      survival, 21% vs 19%; P = .136). Multivariate analysis showed as independent
      predictors of survival age (hazard ratio, 1.05; P = .002), extent of resection
      (hazard ratio, 2.01; P = .026), and presence of residual pN2 (hazard ratio, 1.60;
      P = .047). CONCLUSIONS: After induction therapy for patients with clinical stage
      IIIA disease, both pneumonectomy and lobectomy can be safely performed. Although
      survival after lobectomy is better, long-term survival can be accomplished after
      pneumonectomy for appropriately selected patients. Nodal downstaging is important
      determinant of survival, particularly after lobectomy.

PMID- 21092991
TI  - Third-time lung transplantation in a patient with cystic fibrosis.

PMID- 21092993
TI  - Pericardial effusions in the cancer population: prognostic factors after
      pericardial window and the impact of paradoxical hemodynamic instability.
AB  - OBJECTIVE: In the cancer population, pericardial effusions are a common and
      potentially life-threatening occurrence. Although decompression benefits most
      patients, paradoxical hemodynamic instability (PHI) develops in some, with
      hypotension and shock in the immediate postoperative period. This study examines
      paradoxical hemodynamic instability after pericardial window and identifies
      prognostic factors in patients with cancer who are treated for pericardial
      effusion. METHODS: Retrospective review of 179 consecutive pericardial windows
      performed for pericardial effusion in a tertiary cancer center over a 5-year
      period (January 2004 through March 2009). Demographic, surgical, pathologic, and
      echocardiographic data were analyzed for the end points of paradoxical
      hemodynamic instability (pressor-dependent hypotension requiring intensive care
      unit admission) and overall survival. RESULTS: The most common malignancies were
      lung (44%), breast (20%), hematologic (10%), and gastrointestinal (7%). Overall
      survival for the group was poor (median, 5 months); patients with hematologic
      malignant disease fared significantly better than the others (median survival 36
      months; P = .008). Paradoxical hemodynamic instability occurred in 19 (11%)
      patients. These patients were more likely to have evidence of tamponade on
      echocardiogram (89% vs 56%; P = .005), positive cytology/pathology (68% vs 41%; P
      = .03), and higher volume drained (674 mL vs 495 mL; P = .003). Overall survival
      was significantly shorter in those in whom paradoxical hemodynamic instability
      developed (median survival 35 vs 189 days; hazard ratio = 3; P < .001), and the
      majority of them (11/19, 58%) did not survive their hospitalization. CONCLUSIONS:
      Postoperative hemodynamic instability after pericardial window portends a grave
      prognosis. Evidence of tamponade, larger effusion volumes, and positive cytologic
      findings may predict a higher risk of paradoxical hemodynamic instability and
      anticipate a need for invasive monitoring and intensive care postoperatively.

PMID- 21092994
TI  - Calcified thymoma: an egg in the chest.

PMID- 21092995
TI  - Re: Predicting biochemical recurrence-free survival for patients with positive
      pelvic lymph nodes at radical prostatectomy: C. Von Bodman, G. Godoy, D. C.
      Chade, A. Cronin, L. J. Tafe, S. W. Fine, V. Laudone, P. T. Scardino and J. A.
      Eastham J Urol 2010; 184: 143-148.

PMID- 21092996
TI  - Re: Honor code: H. E. Rushton and H. G. Rushton, Jr. J Urol 2010; 183: 1276-1277.

PMID- 21092997
TI  - Re: Randomized trial of percutaneous tibial nerve stimulation versus sham
      efficacy in the treatment of overactive bladder syndrome: results from the SUmiT
      trial: K. M. Peters, D. J. Carrico, R. A. Perez-Marrero, A. U. Khan, L. S.
      Wooldridge, G. L. Davis and S. A. MacDiarmid J Urol 2010; 183: 1438-1443.

PMID- 21092998
TI  - Arsenic and trace metal contents in sediment profiles from the Admiralty Bay,
      King George Island, Antarctica.
AB  - Admiralty Bay (Antarctica) hosts three scientific stations (Ferraz, Arctowski and
      Macchu Picchu), which require the use of fossil fuel as an energy source. Fossil
      fuels are also considered the main source of pollution in the area, representing
      important inputs of major pollutants (organic compounds) and trace metals and
      metalloids of environmental interest. Accordingly, this work presents the results
      of As, Cd, Cr, Cu, Ni, Pb and Zn in sediment profiles from Admiralty Bay. The
      sediment results from Ferraz station were slightly higher than the other sampling
      sites. The highest contents were observed for Cu and Zn (from 44 to 89 mg kg(
      1)). Otherwise, by using enrichment factors and geochronology analysis, the most
      relevant enrichment was observed for As in the samples collected close to the
      Ferraz station, indicating that increasing As content may be associated with the
      activities associated with this site.

PMID- 21092999
TI  - Diffuse pollution by persistent organic pollutants as measured in plastic pellets
      sampled from various beaches in Greece.
AB  - Plastic pellets found stranded on beaches are hydrophobic organic materials and
      thus, they are a favourable medium for persistent organic pollutants to absorb
      to. In the present study, plastic pellets are used to determine the diffuse
      pollution of selected Greek beaches. Samples of pellets were taken from these
      beaches and were analyzed for PCBs, DDTs, HCHs, and PAHs. The observed
      differences among pellets from various sampling sites are related to the
      pollution occurring at each site. Plastic pellets collected in Saronikos Gulf
      beaches demonstrate much higher pollutant loading than the ones collected in a
      remote island or close to an agricultural area. Based on data collected in this
      study and the International Pellet Watch program, pollution in Saronikos Gulf,
      Greece, is comparable to other heavily industrialized places of the world. The
      present study demonstrates the potential of pellet watch to be utilized as a
      detailed-scale monitoring tool within a single country.

PMID- 21093000
TI  - Establishment of numerical beach-litter hindcast/forecast models: an application
      to Goto Islands, Japan.
AB  - This study attempts to establish a system for hindcasting/forecasting the
      quantity of litter reaching a beach using an ocean circulation model, a two-way
      particle tracking model (PTM) to find litter sources, and an inverse method to
      compute litter outflows at each source. Twelve actual beach survey results, and
      satellite and forecasted wind data were also used. The quantity of beach litter
      was hindcasted/forecasted using a forward in-time PTM with the surface currents
      computed in the ocean circulation model driven by satellite-derived/forecasted
      wind data. Outflows obtained using the inverse method was given for each source
      in the model. The time series of the hindcasted/forecasted quantity of beach
      litter were found consistent with the quantity of beach litter determined from
      sequential webcam images of the actual beach. The accuracy of the model, however,
      is reduced drastically by intense winds such as typhoons which disturb drifting
      litter motion.

PMID- 21093001
TI  - Effects of hyperimmune equine plasma on clinical and cellular responses in a low
      dose endotoxaemia model in horses.
AB  - Endotoxaemia is a major cause of equine morbidity, and plasma from horses
      immunised against Escherichia coli is used in its treatment. The aim of this
      study was to determine the effects of hyperimmune plasma on the clinical and
      leukocyte responses, including production and activity of TNFalpha, in an in vivo
      endotoxin challenge model. Pre-treatment with hyperimmune equine plasma had no
      significant effect on peak total plasma TNFalpha concentration (occurring 90min
      after the administration of 30ng/kg LPS). However, the bioavailable (unbound)
      TNFalpha measured by bioassay was significantly reduced in plasma-treated horses
      (1044.44+/-193.93pg/ml at 90min) compared to saline treated controls (1373.92+/
      107.63pg/ml; P=0.05). Therefore, although pre-treatment with hyperimmune equine
      plasma did not significantly modify the clinical signs of endotoxaemia in this
      model, there was some evidence of reduced TNF bioactivity, which may be due to
      factors in the plasma which bind and reduce the activity of this cytokine.

PMID- 21093002
TI  - Apropos 'Monitoring of poliovirus neutralizing antibodies in Sao Paulo State,
      Brazil'.

PMID- 21093003
TI  - Seasonal prevalence and incidence of Cryptosporidium spp. and Giardia duodenalis
      and associated diarrhoea in children attending pre-school in Kafue, Zambia.
AB  - Prevalence, incidence and seasonal variation of Cryptosporidium and Giardia
      duodenalis were studied over a 12-month period in 100 children from four pre
      schools in Kafue, Zambia. Questionnaire data and a single stool sample were
      collected monthly from each child. Samples were processed using a commercial kit
      (Meridian Diagnostics Inc., USA) and oo(cysts) visualised by immunofluorescence
      microscopy. Cryptosporidium was detected in 30.7% (241/786; 95% CI = 27.5-33.9)
      while G. duodenalis was detected in 29.0% (228/786; 95% CI = 25.8-32.2). A total
      of 86% experienced one or more episodes of cryptosporidiosis while 75% had
      giardiasis. Cumulative incidence per 100 children was 75.4 for Cryptosporidium
      and 49.0 for G. duodenalis. Both infections were significantly more common in the
      wet compared to the dry season (34.8%, 162/466 vs. 24.7%, 79/320, P = 0.003 and
      35.2%, 164/466 vs. 20.0%, 64/320, P < 0.001, respectively). Thus, risk ratios
      (RR) were 1.41 (95% CI = 1.13-1.77) and 1.76 (95% CI = 1.38-2.27) for
      Cryptosporidium and Giardia, respectively. Diarrhoea was significantly associated
      with cryptosporidiosis (RR = 1.23, 95% CI = 1.03-1.47; P = 0.029) but not with
      giardiasis (RR = 1.12, 95% CI = 0.91-1.53; P = 0.26). We conclude that gastro
      intestinal protozoal infections are highly prevalent among children attending pre
      school in peri-urban Zambia highlighting the need for further studies of risk
      factors.

PMID- 21093005
TI  - Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via
      interaction with the viral NS5B protein.
AB  - To identify the host factors implicated in the regulation of hepatitis C virus
      (HCV) genome replication, we performed comparative proteome analyses of HCV
      replication complex (RC)-rich membrane fractions prepared from cells harboring
      genome-length bicistronic HCV RNA at the exponential and stationary growth
      phases. We found that the eukaryotic chaperonin T-complex polypeptide 1 (TCP1)
      ring complex/chaperonin-containing TCP1 (TRiC/CCT) plays a role in the
      replication possibly through an interaction between subunit CCT5 and the viral
      RNA polymerase NS5B. siRNA-mediated knockdown of CCT5 suppressed RNA replication
      and production of the infectious virus. Gain-of-function activity was shown
      following co-transfection with whole eight TRiC/CCT subunits. HCV RNA synthesis
      was inhibited by an anti-CCT5 antibody in a cell-free assay. These suggest that
      recruitment of the chaperonin by the viral nonstructural proteins to the RC,
      which potentially facilitate folding of the RC component(s) into the mature
      active form, may be important for efficient replication of the HCV genome.

PMID- 21093004
TI  - Epstein-Barr Virus nuclear antigen 1 (EBNA1) confers resistance to apoptosis in
      EBV-positive B-lymphoma cells through up-regulation of survivin.
AB  - Resistance to apoptosis is an important component of the overall mechanism which
      drives the tumorigenic process. EBV is a ubiquitous human gamma-herpesvirus which
      preferentially establishes latent infection in viral infected B-lymphocytes.
      EBNA1 is typically expressed in most forms of EBV-positive malignancies and is
      important for replication of the latent episome in concert with replication of
      the host cells. Here, we investigate the effects of EBNA1 on survivin up
      regulation in EBV-infected human B-lymphoma cells. We present evidence which
      demonstrates that EBNA1 forms a complex with Sp1 or Sp1-like proteins bound to
      their cis-element at the survivin promoter. This enhances the activity of the
      complex and up-regulates survivin. Knockdown of survivin and EBNA1 showed
      enhanced apoptosis in infected cells and thus supports a role for EBNA1 in
      suppressing apoptosis in EBV-infected cells. Here, we suggest that EBV encoded
      EBNA1 can contribute to the oncogenic process by up-regulating the apoptosis
      suppressor protein, survivin in EBV-associated B-lymphoma cells.

PMID- 21093006
TI  - Reduced innate immune response, apoptosis, and virus release in cells cured of
      respiratory syncytial virus persistent infection.
AB  - It has been reported that cell clones isolated at different passages from a
      culture of HEp-2 cells infected persistently with human respiratory syncytial
      virus (HRSV) were cured of the virus. Further studies on one of these clones
      (31C1) are reported here, showing that 31C1 cells can still be infected by HRSV
      but release low amounts of virus to the culture supernatant, develop smaller and
      less numerous syncytia than the original HEp-2 cells, and display only a weak
      innate immune response to the infection. Accordingly, uninfected 31C1 cells, but
      not clones derived from uninfected HEp-2 cells, express low levels of TLR3 and
      RIG-I. In addition, 31C1 cells are partly resistant to apoptosis. These results
      indicate that persistent infection of HEp-2 cells by HRSV has selected cell
      variants, with changes affecting cell survival, virus growth and the innate
      immune response that may be valuable for studies of virus-cell interaction.

PMID- 21093007
TI  - Biochemical oxygen demand and nutrient processing in a novel multi-stage raw
      municipal wastewater and acid mine drainage passive co-treatment system.
AB  - A laboratory-scale, four-stage continuous flow reactor system was constructed to
      test the viability of high-strength acid mine drainage (AMD) and municipal
      wastewater (MWW) passive co-treatment. The synthetic AMD had pH 2.60 and 1860
      mg/L acidity as CaCO(3) equivalent with 46, 0.25, 2, 290, 55, 1.2 and 390 mg/L of
      Al, As, Cd, Fe, Mn, Pb and Zn, respectively. The AMD was introduced to the system
      at a 1:2 ratio with raw MWW from the City of Norman, Oklahoma USA containing 265
      +/- 94 mg/L BOD(5), 11.5 +/- 5.3 mg/L PO(4)(-3), and 20.8 +/- 1.8 mg/L NH(4)(+)
      N. During the 135 d experiment, PO(4)(-3) and NH(4)(+)-N were decreased to <0.75
      and 7.4 +/- 1.8 mg/L, respectively. BOD(5) was generally decreased to below
      detection limits. Nitrification increased NO(3)(-) to 4.9 +/- 3.5 mg/L NO(3)(-)
      N, however relatively little denitrification occurred. Results suggest that the
      nitrogen processing community may require an extended period to mature and reach
      full efficiency. Overall, results indicate that passive AMD and MWW co-treatment
      is a viable ecological engineering approach for the developed and developing
      world that can be optimized and applied to improve water quality with minimal use
      of fossil fuels and refined materials.

PMID- 21093008
TI  - Identification of reaction products from reactions of free chlorine with the
      lipid-regulator gemfibrozil.
AB  - High global consumption rates have led to the occurrence of pharmaceutically
      active compounds (PhACs) in wastewater. The use of chlorine to disinfect
      wastewater prior to release into the environment may convert PhACs into
      uncharacterized chlorinated by-products. In this investigation, chlorination of a
      common pharmaceutical, the antihyperlipidemic agent gemfibrozil, was documented.
      Gemfibrozil (2,2-dimethyl-5-(2,5-dimethylphenoxy)pentanoic acid) was reacted with
      sodium hypochlorite and product formation was monitored by gas chromatography
      mass spectrometry (GC-MS). The incorporation of one, two or three chlorine atoms
      into the aromatic region of gemfibrozil was demonstrated using negative-ion
      electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry
      (ESI-MS/MS). Further analysis using (1)H nuclear magnetic resonance (NMR)
      spectroscopy identified the reaction products as 4'-ClGem (5-(4-chloro-2,5
      dimethylphenoxy)-2,2-dimethylpentanoic acid) 4',6'-diClGem (5-(4,6-dichloro-2,5
      dimethylphenoxy)-2,2-dimethylpentanoic acid), and 3',4',6'-triClGem (5-(3,4,6
      trichloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid), products consistent
      with electrophilic aromatic substitution reactions. The rapid reaction of
      gemfibrozil with free chlorine at pH conditions relevant to water treatment
      indicates that a mixture of chlorinated gemfibrozils is likely to be found in
      wastewater disinfected with chlorine.

PMID- 21093009
TI  - The effects of dissolved natural organic matter on the adsorption of synthetic
      organic chemicals by activated carbons and carbon nanotubes.
AB  - Understanding the influence of natural organic matter (NOM) on synthetic organic
      contaminant (SOC) adsorption by carbon nanotubes (CNTs) is important for
      assessing the environmental implications of accidental CNT release and spill to
      natural waters, and their potential use as adsorbents in engineered systems. In
      this study, adsorption of two SOCs by three single-walled carbon nanotubes
      (SWNTs), one multi-walled carbon nanotube (MWNT), a microporous activated carbon
      fiber (ACF) [i.e., ACF10] and a bimodal porous granular activated carbon (GAC)
      [i.e., HD4000] was compared in the presence and absence of NOM. The NOM effect
      was found to depend strongly on the pore size distribution of carbons. Minimal
      NOM effect occurred on the macroporous MWNT, whereas severe NOM effects were
      observed on the microporous HD4000 and ACF10. Although the single-solute
      adsorption capacities of the SWNTs were much lower than those of HD4000, in the
      presence of NOM the SWNTs exhibited adsorption capacities similar to those of
      HD4000. Therefore, if released into natural waters, SWNTs can behave like an
      activated carbon, and will be able to adsorb, carry, and transfer SOCs to other
      systems. However, from an engineering application perspective, CNTs did not
      exhibit a major advantage, in terms of adsorption capacities, over the GAC and
      ACF. The NOM effect was also found to depend on molecular properties of SOCs. NOM
      competition was more severe on the adsorption of 2-phenylphenol, a nonplanar and
      hydrophilic SOC, than phenanthrene, a planar and hydrophobic SOC, tested in this
      study. In terms of surface chemistry, both adsorption affinity to SOCs and NOM
      effect on SOC adsorption were enhanced with increasing hydrophobicity of the
      SWNTs.

PMID- 21093010
TI  - Surveillance of adenoviruses and noroviruses in European recreational waters.
AB  - Exposure to human pathogenic viruses in recreational waters has been shown to
      cause disease outbreaks. In the context of Article 14 of the revised European
      Bathing Waters Directive 2006/7/EC (rBWD, CEU, 2006) a Europe-wide surveillance
      study was carried out to determine the frequency of occurrence of two human
      enteric viruses in recreational waters. Adenoviruses were selected based on their
      near-universal shedding and environmental survival, and noroviruses (NoV)
      selected as being the most prevalent gastroenteritis agent worldwide.
      Concentration of marine and freshwater samples was done by adsorption/elution
      followed by molecular detection by (RT)-PCR. Out of 1410 samples, 553 (39.2%)
      were positive for one or more of the target viruses. Adenoviruses, detected in
      36.4% of samples, were more prevalent than noroviruses (9.4%), with 3.5% GI and
      6.2% GII, some samples being positive for both GI and GII. Of 513 human
      adenovirus-positive samples, 63 (12.3%) were also norovirus-positive, whereas 69
      (7.7%) norovirus-positive samples were adenovirus-negative. More freshwater
      samples than marine water samples were virus-positive. Out of a small selection
      of samples tested for adenovirus infectivity, approximately one-quarter were
      positive. Sixty percent of 132 nested-PCR adenovirus-positive samples analysed by
      quantitative PCR gave a mean value of over 3000 genome copies per L of water. The
      simultaneous detection of infectious adenovirus and of adenovirus and NoV by
      (RT)PCR suggests that the presence of infectious viruses in recreational waters
      may constitute a public health risk upon exposure. These studies support the case
      for considering adenoviruses as an indicator of bathing water quality.

PMID- 21093011
TI  - Quantitative and qualitative analyses of methanogenic community development in
      high-rate anaerobic bioreactors.
AB  - Methanogenic community structure and population dynamics were investigated in two
      anaerobic reactors treating a dairy wastewater, an Inverted Fluidized Bed (IFB)
      and Expanded Granular Sludge Bed (EGSB). A combination of real-time PCR,
      denaturing gradient gel electrophoresis and statistical techniques was employed.
      Distinct methanogenic communities developed in the IFB and EGSB reactors
      reflecting step-wise reductions in the applied hydraulic retention time from 72
      to 12 h during the 200-day trial. The aceticlastic family Methanosarcinaceae was
      only detected in the IFB and the order Methanomicrobiales was also much more
      abundant in this reactor, while the aceticlastic family Methanosaetaceae was more
      abundant in the EGSB. The hydrogenotrophic order, Methanobacteriales,
      predominated in both reactors under all applied operational conditions. Non
      metric multidimensional scaling (NMS) and moving-window analyses, based on
      absolute and relative abundance quantification data, demonstrated that the
      methanogenic communities developed in a different manner in the IFB, compared to
      the EGSB reactor. In our study, relative abundance-based quantification by NMS
      and moving-window analysis appeared to be a valuable molecular approach that was
      more applicable to reflect the changes in the anaerobic digestion process than
      approaches based either on qualitative analysis, or solely on absolute
      quantification of the various methanogenic groups. The overall results and
      findings provided a comparative, quantitative and qualitative insight into
      anaerobic digestion processes, which could be helpful for better future reactor
      design and process control.

PMID- 21093012
TI  - Efficiency of water disinfectants against Legionella pneumophila and
      Acanthamoeba.
AB  - Free-living amoebae might be pathogenic by themselves and be a reservoir for
      bacterial pathogens, such as Legionella pneumophila. Not only could amoebae
      protect intra-cellular Legionella but Legionella grown within amoebae could
      undergo physiological modifications and become more resistant and more virulent.
      Therefore, it is important to study the efficiency of treatments on amoebae and
      Legionella grown within these amoebae to improve their application and to limit
      their impact on the environment. With this aim, we compared various water
      disinfectants against trophozoites of three Acanthamoeba strains and L.
      pneumophila alone or in co-culture. Three oxidizing disinfectants (chlorine,
      monochloramine, and chlorine dioxide) were assessed. All the samples were treated
      with disinfectants for 1 h and the disinfectant concentration was followed to
      calculate disinfectant exposure (Ct). We noticed that there were significant
      differences of susceptibility among the Acanthamoeba strains. However no
      difference was observed between infected and non-infected amoebae. Also, the
      comparison between the three disinfectants indicates that monochloramine was
      efficient at the same level towards free or co-cultured L. pneumophila while
      chlorine and chlorine dioxide were less efficient on co-cultured L. pneumophila.
      It suggests that these disinfectants should have different modes of action.
      Finally, our results provide for the first time disinfectant exposure values for
      Acanthamoeba treatments that might be used as references for disinfection of
      water systems.

PMID- 21093013
TI  - Effect of selected metal ions on the photocatalytic degradation of bog lake water
      natural organic matter.
AB  - Herein we report the photocatalytic degradation of natural organic matter from a
      bog lake (Lake Hohloh, Black Forest, Germany) in the presence of 0, 5, and 10
      MUmol L(-1) of added Cu(2+), Mn(2+), Zn(2+) and Fe(3+). The reactions were
      followed by size exclusion chromatography with organic carbon detection (SEC-DOC)
      and by measurements of low molecular weight organic acids. Addition of Cu(2+) had
      the largest effect of all four studied metals, leading to a retardation in the
      molecular size changes in NOM: degradation of the larger molecular weight
      fraction was inhibited leading to reduced production of smaller molecular weight
      metabolites. Similarly, addition of Cu(2+) reduced the production of formic and
      oxalic acids, and reduced the bioavailability of the partially degraded NOM.

PMID- 21093014
TI  - Ecological divergence and medial cuneiform morphology in gorillas.
AB  - Gorillas are more closely related to each other than to any other extant primate
      and are all terrestrial knuckle-walkers, but taxa differ along a gradient of
      dietary strategies and the frequency of arboreality in their behavioral
      repertoire. In this study, we test the hypothesis that medial cuneiform
      morphology falls on a morphocline in gorillas that tracks function related to
      hallucial abduction ability and relative frequency of arboreality. This
      morphocline predicts that western gorillas, being the most arboreal, should
      display a medial cuneiform anatomy that reflects the greatest hallucial abduction
      ability, followed by grauer gorillas, and then by mountain gorillas. Using a
      three-dimensional methodology to measure angles between articular surfaces,
      relative articular and nonarticular areas, and the curvatures of the hallucial
      articular surface, the functional predictions are partially confirmed in
      separating western gorillas from both eastern gorillas. Western gorillas are
      characterized by a more medially oriented, proportionately larger, and more
      mediolaterally curved hallucial facet than are eastern gorillas. These
      characteristics follow the predictions for a more prehensile hallux in western
      gorillas relative to a more stable, plantigrade hallux in eastern gorillas. The
      characteristics that distinguish eastern gorilla taxa from one another appear
      unrelated to hallucial abduction ability or frequency of arboreality. In total,
      this reexamination of medial cuneiform morphology suggests differentiation
      between eastern and western gorillas due to a longstanding ecological divergence
      and more recent and possibly non-adaptive differences between eastern taxa.

PMID- 21093015
TI  - Skhodnya, Khvalynsk, Satanay, and Podkumok calvariae: possible Upper Paleolithic
      hominins from European Russia.
AB  - European Russia has been at the fringe of the hominin dispersal for most of the
      late Pleistocene. However, by about 20,000 BP this area was settled by modern
      humans who had highly sophisticated and sometimes unique technologies. Not many
      Upper Paleolithic human fossils have been described from this area and
      consequently the morphology of these people remains largely unknown. Here, we
      present descriptions and a comparative morphological analysis of four possibly
      late Pleistocene fossils from European Russia: Skhodnya, Khvalynsk, Satanay, and
      Podkumok. The frontal bone is chosen for study because it is preserved in all of
      these fossils and is known to provide good discrimination among groups of
      Pleistocene hominins. All four fossils have been previously claimed to possess
      'archaic' features of frontal morphology, such as developed supraorbital relief
      and a flat frontal squama. The results of a 3D geometric morphometric analysis of
      frontal bone landmarks and semilandmarks indicate that these fossils indisputably
      belong to modern humans. However, there are good reasons to associate Khvalynsk,
      Skhodnya, and Podkumok with Upper Paleolithic fossils from central and western
      Europe, whereas Satanay is more similar to a pooled sample of recent modern
      humans.

PMID- 21093016
TI  - What can be learnt from an ecotoxicity database in the framework of the REACh
      regulation?
AB  - Since REACh applies in all of EU, special emphasis has been put on the reduction
      of systematic ecotoxicity testing. In this context, it is important to extract a
      maximum of information from existing ecotoxicity databases in order to propose
      alternative methods aimed at replacing and reducing experimental testing.
      Consequently, we analyzed a database of new chemicals registered in France and
      Europe during the last twenty years reporting aquatic ecotoxicity data with
      respect to three trophic levels (i.e., Algae EC50 72 h, Daphnia EC50 48 h and
      Fish LC50 96 h). In order to ensure the relevance of the comparison between these
      three experimental tests, we performed a stringent data selection based on the
      pertinence and quality of available ecotoxicological information. At the end of
      this selection, less than 5% of the initial number of chemicals was retained for
      subsequent analysis. Such an analysis showed that fish was the least sensitive
      trophic level, whereas Daphnia had the highest sensitivity. Moreover, thanks to
      an analysis of the relative sensitivity of trophic levels, it was possible to
      establish that respective correction factors of 50 and 10 would be necessary if
      only one or two test values were available. From a physicochemical point of view,
      it was possible to characterize two significant correlations relating the
      sensitivity of the aforementioned trophic levels with the chemical structure of
      the retained substances. This analysis showed that algae displayed a higher
      sensitivity towards chemicals containing acid fragments whereas fish presented a
      higher sensitivity towards chemicals containing aromatic ether fragments.
      Overall, our work suggests that statistical analysis of historical data combined
      with data yielded by the REACh regulation should permit the derivation of robust
      safety factors, testing strategies and mathematical models. These alternative
      methods, in turn, could allow a replacement and reduction of ecotoxicological
      testing.

PMID- 21093017
TI  - Metal content of charcoal in mining-impacted wetland sediments.
AB  - Charcoal is well known to accumulate contaminants, but its association with
      metals and other toxic elements in natural settings has not been well studied.
      Association of contaminants with charcoal in soil and sediment may affect their
      mobility, bioavailability, and fate in the environment. In this paper, natural
      wildfire charcoal samples collected from a wetland site that has been heavily
      contaminated by mine waste were analyzed for elemental contents and compared to
      the surrounding soil. Results showed that the charcoal particles were enriched
      over the host soils by factors of two to 40 times in all contaminant elements
      analyzed. Principal component analysis was carried out on the data to determine
      whether element enrichment patterns in the soil profile charcoal are related to
      those in the soils. The results suggest that manganese and zinc concentrations in
      charcoal are controlled by geochemical processes in the surrounding soil, whereas
      the concentrations of arsenic, lead, zinc, iron, phosphorus, and sulfur in
      charcoal are unrelated to those in the surrounding soil. This study shows
      evidence that charcoal in soils can have a distinct and important role in
      controlling contaminant speciation and fate in the environment.

PMID- 21093018
TI  - Assessing the fate of antibiotic contaminants in metal contaminated soils four
      years after cessation of long-term waste water irrigation.
AB  - Spreading of urban wastewater on agricultural land may lead to concomitant input
      of organic and inorganic pollutants. Such multiple pollution sites offer unique
      opportunities to study the fate of both heavy metals and pharmaceuticals. We
      examined the occurrence and fate of selected antibiotics in sandy-textured soils,
      sampled four years after cessation of 100 years irrigation with urban wastewater
      from the Paris agglomeration. Previous studies on heavy metal contamination of
      these soils guided our sampling strategy. Six antibiotics were studied, including
      quinolones, with a strong affinity for organic and mineral soil components, and
      sulfonamides, a group of more mobile molecules. Bulk samples were collected from
      surface horizons in different irrigation fields, but also in subsurface horizons
      in two selected profiles. In surface horizons, three quinolones (oxolinic acid,
      nalidixic acid, and flumequine) were present in eight samples out of nine. Their
      contents varied spatially, but were well-correlated one to another. Their
      distributions showed great similarities regarding spatial distribution of total
      organic carbon and heavy metal contents, consistent with a common origin by
      wastewater irrigation. Highest concentrations were observed for sampling sites
      close to irrigation water outlets, reaching 22 MUg kg(-1) for nalidixic acid.
      Within soil profiles, the two antibiotic groups demonstrated an opposite
      behavior: quinolones, found only in surface horizons; sulfamethoxazole, detected
      in clay-rich subsurface horizons, concomitant with Zn accumulation. Such
      distribution patterns are consistent with chemical adsorption properties of the
      two antibiotic groups: immobilization of quinolones in the surface horizons
      ascribed to strong affinity for organic matter (OM), migration of
      sulfamethoxazole due to a lower affinity for OM and its interception and
      retention in electronegative charged clay-rich horizons. Our work suggests that
      antibiotics may represent a durable contamination of soils, and risks for
      groundwater contamination, depending on the physicochemical characteristics both
      of the organic molecules and of soil constituents.

PMID- 21093019
TI  - Removal of atrazine by nanoscale zero valent iron supported on organobentonite.
AB  - The organobentonite (CTMA-Bent) was prepared from Na(+)-saturated bentonite (Na
      Bent) by intercalation with cetyltrimethylammonium bromide (CTMA), and used as a
      carrier of nanoscale zero valent iron (NZVI) for the removal of atrazine. The
      NZVI/CTMA-Bent composite was characterized by X-ray diffraction (XRD) and
      transmission electron microscope (TEM), and good dispersion of nanoscale iron
      particles on the carrier was observed. The removal efficiency of atrazine by this
      composite was compared with that by commercial iron powder and NZVI itself. For
      both treatments by NZVI and NZVI/CTMA-Bent, the removal efficiency increased as
      the pH of the solution decreased, and the removal percentage of atrazine by
      NZVI/CTMA-Bent reached 63.5% at initial pH=5.0 after 120 min. It is not only much
      higher than that (26.6%) by NZVI containing the same amount of iron, but also
      superior to the sum (32.1%) of reduction by NZVI plus adsorption by CTMA-Bent
      (5.5%). Besides, the NZVI/CTMA-Bent has a good long-term stability, and the
      carrier CTMA-Bent could prevent the iron ions (the byproduct of dechlorination)
      from leaching into the solution.

PMID- 21093021
TI  - Patient characteristics associated with allergen immunotherapy initiation and
      adherence.

PMID- 21093020
TI  - Cancer in patients with rheumatic diseases exposed to TNF antagonists.
AB  - OBJECTIVE: To describe the risk of cancer in patients exposed to tumor necrosis
      factor (TNF) antagonists. METHODS: The following 2 clinical cohorts were studied:
      (1) BIOBADASER 2.0: a registry of patients suffering from rheumatic diseases
      exposed to TNF antagonists (2531 rheumatoid arthritis (RA), 1488
      spondyloarthropathies, and 675 other rheumatic conditions); and (2) EMECAR: a
      cohort of 789 RA patients not exposed to TNF antagonists. Cancer incidence rates
      (IR) per 1000 patient-years and incidence rate ratios (IRR) were calculated for
      BIOBADASER 2.0 and EMECAR patients. The IR over time in BIOBADASER 2.0 patients
      was analyzed by joinpoint regression. The IRR was estimated to compare cancer
      rates in exposed versus nonexposed RA patients. Standardized incidence and
      mortality ratios (SIR, SMR) were also estimated. Risk factors for cancer in
      patients exposed to TNF antagonists were investigated by generalized linear
      models. RESULTS: The SMR for cancer in BIODASER 2.0 was 0.67 (95% CI: 0.51-0.86),
      and the SIR was 0.1 (95% CI 0.03-0.23). The IR in RA patients exposed to TNF
      antagonists was 5.8 (95% CI: 4.4-7.6), and the adjusted IRR was 0.48 (95% CI:
      0.09-2.45). The IR in patients with previous cancer was 26.4 (95% CI: 4.1-171.5).
      Age, chronic obstructive pulmonary disease, and steroids were associated with a
      higher risk of developing cancer. The IR decreased after the first 4 months of
      exposure, without statistical significance. CONCLUSION: Overall cancer and
      mortality rates in patients with rheumatic diseases exposed to TNF antagonists
      are no higher than in the background Spanish population. However special
      attention should be paid to elderly patients, those with previous cancers, and
      patients treated with steroids.

PMID- 21093023
TI  - Dexamethasone regulation of thymic stromal lymphopoietin receptor expression on
      mast cells and their precursors.

PMID- 21093024
TI  - Use of the Asthma Control Questionnaire to predict future risk of asthma
      exacerbation.
AB  - BACKGROUND: Direct correlation of assessments of a validated composite measure
      such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not
      been previously demonstrated in a randomized controlled trial. OBJECTIVE: To
      evaluate the ability of the ACQ score over time to predict risk of a future
      asthma exacerbation. METHODS: This analysis included data from a 12-week placebo
      controlled trial (N = 292) of AMG 317, an IL-4 receptor alpha antagonist, in
      patients with moderate to severe atopic asthma. At baseline, patients had an ACQ
      score >=1.5. Exacerbations were defined as requirement for systemic
      corticosteroids. A Cox proportional hazards model was used, with ACQ score as the
      time-dependent covariate. The analysis was repeated for individual components of
      the ACQ. RESULTS: Each 1-point increase in ACQ was associated with a 50%
      increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the
      following 2-week period. Evaluation of individual ACQ components also
      demonstrated a similar trend, though each to a lesser degree than the full
      composite ACQ. CONCLUSION: Although based on a retrospective analysis, with small
      number of exacerbations, these findings support the utility of the composite ACQ
      score measurement to predict risk of future exacerbation in clinical trials and
      clinical practice. The composite ACQ score measurement was found to be a better
      predictor of future risk than individual ACQ components.

PMID- 21093025
TI  - Ara h 2 peptides containing dominant CD4+ T-cell epitopes: candidates for a
      peanut allergy therapeutic.
AB  - BACKGROUND: Peanut allergy is a life-threatening condition; there is currently no
      cure. Although whole allergen extracts are used for specific immunotherapy for
      many allergies, they can cause severe reactions, and even fatalities, in peanut
      allergy. OBJECTIVE: This study aimed to identify short, T-cell epitope-based
      peptides that target allergen-specific CD4(+) T cells but do not bind IgE as
      candidates for safe peanut-specific immunotherapy. METHODS: Multiple CD4(+) T
      cell lines specific for the major peanut allergen Ara h 2 were generated from
      PBMCs of 16 HLA-diverse subjects with peanut allergy by using 5,6
      carboxyfluorescein diacetate succinimidylester-based methodology. Proliferation
      and ELISPOT assays were used to identify dominant epitopes recognized by T-cell
      lines and to confirm recognition by peripheral blood T cells of epitope-based
      peptides modified for therapeutic production. HLA restriction of core epitope
      recognition was investigated by using anti-HLA blocking antibodies and HLA
      genotyping. Serum-IgE peptide-binding was assessed by dot-blot. RESULTS: Five
      dominant CD4(+) T-cell epitopes were identified in Ara h 2. In combination, these
      were presented by HLA-DR, HLA-DP, and HLA-DQ molecules and recognized by T cells
      from all 16 subjects. Three short peptide variants containing these T-cell
      epitopes were designed with cysteine-to-serine substitutions to facilitate
      stability and therapeutic production. Variant peptides showed HLA-binding
      degeneracy, did not bind peanut-specific serum IgE, and could directly target
      T(H)2-type T cells in peripheral blood of subjects with allergy. CONCLUSION:
      Short CD4(+) T-cell epitope-based Ara h 2 peptides were identified as novel
      candidates for a T-cell-targeted peanut-specific immunotherapy for an HLA-diverse
      population.

PMID- 21093027
TI  - Paracetamol, nonsteroidal anti-inflammatory drugs, and risk of asthma in adult
      survivors of childhood cancer.

PMID- 21093026
TI  - Peanut allergy: Clinical and immunologic differences among patients from 3
      different geographic regions.
AB  - BACKGROUND: Peanut allergy affects persons from various geographic regions where
      populations are exposed to different dietary habits and environmental pollens.
      OBJECTIVE: We sought to describe the clinical and immunologic characteristics of
      patients with peanut allergy from 3 countries (Spain, the United States, and
      Sweden) using a molecular component diagnostic approach. METHODS: Patients with
      peanut allergy from Madrid (Spain, n = 50), New York (United States, n = 30),
      Gothenburg, and Stockholm (both Sweden, n = 35) were enrolled. Clinical data were
      obtained either from a specific questionnaire or gathered from chart reviews. IgE
      antibodies to peanut extract and the peanut allergens rAra h 1, 2, 3, 8 and 9, as
      well as to cross-reactive birch (rBet v 1) and grass (rPhl p 1, 5, 7, and 12)
      pollen allergens, were analyzed. RESULTS: American patients frequently had IgE
      antibodies to rAra h 1 to 3 (56.7% to 90.0%) and often presented with severe
      symptoms. Spanish patients recognized these 3 recombinant peanut allergens less
      frequently (16.0% to 42.0%), were more often sensitized to the lipid transfer
      protein rAra h 9 (60.0%), and typically had peanut allergy after becoming
      allergic to other plant-derived foods. Swedish patients detected rAra h 1 to 3
      more frequently than Spanish patients (37.1% to 74.3%) and had the highest
      sensitization rate to the Bet v 1 homologue rAra h 8 (65.7%), as well as to rBet
      v 1 (82.9%). Spanish and Swedish patients became allergic to peanut at 2 years or
      later, whereas the American children became allergic around 1 year of age.
      CONCLUSIONS: Peanut allergy has different clinical and immunologic patterns in
      different areas of the world. Allergen component diagnostics might help us to
      better understand this complex entity.

PMID- 21093028
TI  - Occupational endotoxin exposure and a novel luminol-enhanced chemiluminescence
      assay of nasal lavage neutrophil activation.

PMID- 21093029
TI  - Single-tree nut immunotherapy attenuates allergic reactions in mice with
      hypersensitivity to multiple tree nuts.
AB  - BACKGROUND: Allergic reactions to tree nuts are often severe and are outgrown in
      less than 10% of diagnosed patients. OBJECTIVES: To determine whether treatment
      of underlying tree nut sensitization will prevent allergic reactions to cross
      reacting tree nuts and to determine the effects of single-tree nut immunotherapy
      on true multi-tree nut sensitization. METHODS: Cross-reactivity model: Cashew
      sensitized mice underwent immunotherapy with cashew and were subsequently
      challenged with cashew and pistachio. Multisensitization model: Cashew plus
      walnut-sensitized mice were treated with cashew alone, walnut alone, or both
      cashew and walnut and then underwent challenges to cashew and walnut. Challenges
      were assessed on the basis of symptoms, changes in body temperature, and mouse
      mast cell protease-1 release. RESULTS: In the cross-reactivity model, cashew
      immunotherapy completely prevented allergic reactions on challenges with cashew
      or the cross-reactive pistachio. In the multisensitization model, mice with
      cashew plus walnut allergy were significantly protected from anaphylactic
      reactions on cashew challenge in both the cashew-alone and walnut-alone
      immunotherapy groups. Results from the walnut challenge demonstrated
      significantly decreased allergic responses in the walnut immunotherapy group,
      whereas mice in the cashew immunotherapy group experienced significantly lower
      symptoms. In the cross-reactivity model, immunotherapy effectively decreased IL-4
      and IL-5 production and increased IL-12 relative to placebo while also inducing a
      5-fold increase in specific IgG(1). CONCLUSION: Single-tree nut immunotherapy can
      effectively decrease allergic responses in both the cross-reactivity and
      multisensitization mouse models. Further studies are needed to determine which
      single-tree nut immunotherapies will be most effective for specific multi-tree
      nut allergy profiles.

PMID- 21093030
TI  - Differences in innate immune function between allergic and nonallergic children:
      new insights into immune ontogeny.
AB  - BACKGROUND: Microbial products are of central interest in the modulation of
      allergic propensity. OBJECTIVE: We sought to explore whether allergic children
      show differences in microbial Toll-like receptor (TLR)-mediated responses over
      their first 5 years of life. METHODS: Mononuclear cells isolated from 35 allergic
      and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were
      stimulated with TLR2-TLR9 ligands to study innate immune function and with
      allergens or mitogen to assess adaptive T-cell responses. Cytokine production was
      measured by using Luminex multiplexing technology. RESULTS: Nonallergic children
      show progressive and significant age-related increases in innate cytokine
      responses (IL-1beta, IL-6, TNF-alpha, and IL-10) to virtually all TLR ligands.
      This innate maturation corresponds with a parallel increase in adaptive T(H)1
      (IFN-gamma) responses to allergens and mitogens. In contrast, allergic children
      show exaggerated innate responses at birth (P < .01) but a relative decrease with
      age thereafter, so that by age 5 years, TLR responses are attenuated compared
      with those seen in nonallergic subjects (P < .05). This early hyperresponsiveness
      in allergic subjects fails to translate to a corresponding maturation of T(H)1
      function, which remains attenuated relative to that seen in nonallergic subjects
      but is associated with a characteristic age-dependent increase in allergen
      specific T(H)2 responses (P < .01). CONCLUSION: Our findings suggest significant
      differences in the developmental trajectory of innate immune function in children
      with allergic disease that might contribute to the recognized differences in
      postnatal adaptive T-cell immunity.

PMID- 21093031
TI  - A lower prevalence of asthma among patients with chronic rhinosinusitis in
      southern China.

PMID- 21093032
TI  - The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous
      candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity.

PMID- 21093033
TI  - The effect of prophylactic palivizumab on recurrent wheezing in children with an
      atopic family history.

PMID- 21093034
TI  - Resin composite--state of the art.
AB  - OBJECTIVES: The objective is to review the current state of the art of dental
      composite materials. METHODS: An outline of the most important aspects of dental
      composites was created, and a subsequent literature search for articles related
      to their formulation, properties and clinical considerations was conducted using
      PubMed followed by hand searching citations from relevant articles. RESULTS: The
      current state of the art of dental composites includes a wide variety of
      materials with a broad range of mechanical properties, handling characteristics,
      and esthetic possibilities. This highly competitive market continues to evolve,
      with the major emphasis in the past being to produce materials with adequate
      strength, and high wear resistance and polishability retention. The more recent
      research and development efforts have addressed the issue of polymerization
      shrinkage and its accompanying stress, which may have a deleterious effect on the
      composite/tooth interfacial bond. Current efforts are focused on the delivery of
      materials with potentially therapeutic benefits and self-adhesive properties, the
      latter leading to truly simplified placement in the mouth. SIGNIFICANCE: There is
      no one ideal material available to the clinician, but the commercial materials
      that comprise the current armamentarium are of high quality and when used
      appropriately, have proven to deliver excellent clinical outcomes of adequate
      longevity.

PMID- 21093035
TI  - Surface integrity of solvent-challenged ormocer-matrix composite.
AB  - OBJECTIVE: To investigate the surface integrity of solvent-challenged ormocer
      matrix composites, photoactivated by different light exposure modes, through
      surface-hardness measurements at different periods of time; and to compare such
      behavior with dimethacrylate-based materials. METHODS: One hundred percent
      ormocer-based matrix (experimental ormocer (ORM)), a commercial mixed
      dimethacrylate-ormocer-based matrix (Admira (ADR)) and two commercial
      dimethacrylate-based matrix composites (experimental controls, (Grandio (GRD) and
      Premise (PRE)) were evaluated. Disk specimens (4 mm * 2 mm) were prepared from
      each material and light-activated using either a standard (S) or soft-start (SS)
      light exposure protocol with an LED-curing unit. Top, irradiated surface Knoop
      hardness (KHN) was measured within the following experimental groups (n=5): Group
      1: immediately after exposure; Group 2: after dry and dark storage, Group 3:
      after storage in distilled water, and Group 4: immersion in absolute ethanol.
      Hardness of Groups 2-4 were measured after 7 days storage. Immediate hardness
      values were submitted to Student's t-tests separately for each material. Hardness
      values after treatments were submitted to two-way ANOVA and Tukey's post hoc test
      to compare values among different storage media and light exposure mode
      protocols. Comparisons among materials were described using percentage of
      hardness change. Statistical testing was performed at a pre-set alpha of 0.05.
      RESULTS: Immediate hardness values were not affected by the light exposure mode,
      regardless of the material. In general, exposure mode did not significantly
      affect hardness after 7 days storage, regardless of storage media or material.
      After 7 days dry storage, hardness values increased for all materials relative to
      immediate testing, and decreased after water and ethanol storage, with ethanol
      showing the greatest effect. The experimental ormocer-based material had the
      lowest percentage hardness change and thus proved more resistant to solvent
      degradation than the other materials, regardless of the light exposure method.
      SIGNIFICANCE: Irradiated surface hardness values and surface integrity were
      unaffected by light exposure mode, regardless of the material tested. The
      experimental ormocer-based material presented the least change in hardness as a
      result of solvent challenge than any of the commercial products: ormocer or
      conventional resin-based, and thus showed better surface integrity.

PMID- 21093037
TI  - Renal sympathetic denervation: the jury is still out.

PMID- 21093036
TI  - Renal sympathetic denervation in patients with treatment-resistant hypertension
      (The Symplicity HTN-2 Trial): a randomised controlled trial.
AB  - BACKGROUND: Activation of renal sympathetic nerves is key to pathogenesis of
      essential hypertension. We aimed to assess effectiveness and safety of catheter
      based renal denervation for reduction of blood pressure in patients with
      treatment-resistant hypertension. METHODS: In this multicentre, prospective,
      randomised trial, patients who had a baseline systolic blood pressure of 160 mm
      Hg or more (>=150 mm Hg for patients with type 2 diabetes), despite taking three
      or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to
      undergo renal denervation with previous treatment or to maintain previous
      treatment alone (control group) at 24 participating centres. Randomisation was
      done with sealed envelopes. Data analysers were not masked to treatment
      assignment. The primary effectiveness endpoint was change in seated office-based
      measurement of systolic blood pressure at 6 months. Primary analysis included all
      patients remaining in follow-up at 6 months. This trial is registered with
      ClinicalTrials.gov, number NCT00888433. FINDINGS: 106 (56%) of 190 patients
      screened for eligibility were randomly allocated to renal denervation (n=52) or
      control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52
      patients who underwent renal denervation and 51 (94%) of 54 controls were
      assessed for the primary endpoint at 6 months. Office-based blood pressure
      measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11,
      baseline of 178/96 mm Hg, p<0.0001), whereas they did not differ from baseline in
      the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0.77
      systolic and p=0.83 diastolic). Between-group differences in blood pressure at 6
      months were 33/11 mm Hg (p<0.0001). At 6 months, 41 (84%) of 49 patients who
      underwent renal denervation had a reduction in systolic blood pressure of 10 mm
      Hg or more, compared with 18 (35%) of 51 controls (p<0.0001). We noted no serious
      procedure-related or device-related complications and occurrence of adverse
      events did not differ between groups; one patient who had renal denervation had
      possible progression of an underlying atherosclerotic lesion, but required no
      treatment. INTERPRETATION: Catheter-based renal denervation can safely be used to
      substantially reduce blood pressure in treatment-resistant hypertensive patients.
      FUNDING: Ardian.

PMID- 21093038
TI  - Doctors and climate change.

PMID- 21093039
TI  - Plastic particles in coastal pelagic ecosystems of the Northeast Pacific ocean.
AB  - The purpose of this study was to examine the distribution, abundance and
      characteristics of plastic particles in plankton samples collected routinely in
      Northeast Pacific ecosystems, and to contribute to the development of ideas for
      future research into the occurrence and impact of small plastic debris in marine
      pelagic ecosystems. Plastic debris particles were assessed from zooplankton
      samples collected as part of the National Oceanic and Atmospheric
      Administration's (NOAA) ongoing ecosystem surveys during two research cruises in
      the Southeast Bering Sea in the spring and fall of 2006 and four research cruises
      off the U.S. west coast (primarily off southern California) in spring, summer and
      fall of 2006, and in January of 2007. Nets with 0.505 mm mesh were used to
      collect surface samples during all cruises, and sub-surface samples during the
      four cruises off the west coast. The 595 plankton samples processed indicate that
      plastic particles are widely distributed in surface waters. The proportion of
      surface samples from each cruise that contained particles of plastic ranged from
      8.75 to 84.0%, whereas particles were recorded in sub-surface samples from only
      one cruise (in 28.2% of the January 2007 samples). Spatial and temporal
      variability was apparent in the abundance and distribution of the plastic
      particles and mean standardized quantities varied among cruises with ranges of
      0.004-0.19 particles/m3, and 0.014-0.209 mg dry mass/m3. Off southern California,
      quantities for the winter cruise were significantly higher, and for the spring
      cruise significantly lower than for the summer and fall surveys (surface data).
      Differences between surface particle concentrations and mass for the Bering Sea
      and California coast surveys were significant for pair-wise comparisons of the
      spring but not the fall cruises. The particles were assigned to three plastic
      product types: product fragments, fishing net and line fibers, and industrial
      pellets; and five size categories: <1 mm, 1-2.5 mm, >2.5-5 mm, >5-10 mm, and >10
      mm. Product fragments accounted for the majority of the particles, and most were
      less than 2.5 mm in size. The ubiquity of such particles in the survey areas and
      predominance of sizes <2.5 mm implies persistence in these pelagic ecosystems as
      a result of continuous breakdown from larger plastic debris fragments, and
      widespread distribution by ocean currents. Detailed investigations of the trophic
      ecology of individual zooplankton species, and their encounter rates with various
      size ranges of plastic particles in the marine pelagic environment, are required
      in order to understand the potential for ingestion of such debris particles by
      these organisms. Ongoing plankton sampling programs by marine research institutes
      in large marine ecosystems are good potential sources of data for continued
      assessment of the abundance, distribution and potential impact of small plastic
      debris in productive coastal pelagic zones.

PMID- 21093040
TI  - An energy budget for the subtidal bivalve Modiolus barbatus (Mollusca) at
      different temperatures.
AB  - Clearance rates, respiration rates and food absorption efficiencies of the
      commercially interesting subtidal bivalve Modiolus barbatus were measured at
      different temperatures under laboratory conditions and scope for growth
      calculated. Clearance rates were highest at temperatures from 20  degrees C to 28
      degrees C, whereas respiration rate was maximal at 9  degrees C and minimal at
      26  degrees C. Highest mean values of absorbed energy occurred at 20  degrees C
      and 26  degrees C. Scope for growth trend had negative values at 9  degrees C, 15
      degrees C and 28  degrees C and positive values at temperatures 20  degrees C
      and 26  degrees C. The profitable thermal window for M. barbatus to have energy
      sufficient for growth and reproduction corresponded to <5 months per year.
      Seawater temperature increases will potentially impact the eco-physiological
      responses of subtidal M. barbatus causing life history traits to change with
      important repercussions for subtidal biodiversity in the Mediterranean.

PMID- 21093041
TI  - Multi-functional liposomes having temperature-triggered release and magnetic
      resonance imaging for tumor-specific chemotherapy.
AB  - For development of tumor-specific chemotherapy, we designed liposomes with
      temperature-triggered drug release and magnetic resonance imaging (MRI)
      functions. We prepared multi-functional liposomes by incorporating
      thermosensitive poly(2-ethoxy(ethoxyethyl)vinyl ether) chains with a lower
      critical solution temperatures around 40  degrees C and polyamidoamine G3 dendron
      based lipids having Gd(3+) chelate residues into pegylated liposomes. These
      stable doxorubicin (DOX)-loaded liposomes retained DOX in their interior below
      physiological temperature but released DOX immediately at temperatures greater
      than 40  degrees C. They exhibited excellent ability to shorten the longitudinal
      proton relaxation time. When administered intravenously into colon 26 tumor
      bearing mice, accumulated liposomes in tumors increased with time, reaching a
      constant level 8 h after administration by following T(1)-weighted MRI signal
      intensity in tumors. Liposome size affected the liposome accumulation efficiency
      in tumors: liposomes of about 100 nm diameter were accumulated more efficiently
      than those with about 50 nm diameter. Tumor size also affected accumulation: more
      efficient accumulation occurred in larger tumors. Tumor growth was strongly
      suppressed when liposomes loaded with DOX were administered intravenously into
      tumor-bearing mice and the tumor was heated mildly at 44  degrees C for 10 min at
      8 h after administration. Multi-functional liposomes having temperature-triggered
      drug release and MRI functions might engender personalized chemotherapy,
      providing efficient patient-optimized chemotherapy.

PMID- 21093043
TI  - Protein adsorption and complement activation for di-block copolymer
      nanoparticles.
AB  - Four types of nanoparticles with core-diffuse shell structures have been
      synthesized through self-assembly of PICBA-Dextran block copolymers. These
      nanoparticles are designed to carry pharmaceutically active molecules into the
      human body through injection into the blood stream. In this work, we have
      determined how the characteristics of the diffuse shell influence the adsorption
      of three types of proteins: Bovine Serum Albumin (BSA), fibrinogen, and a protein
      from the complement system that triggers recognition and elimination by
      macrophages. We have determined the structural characteristics of the diffuse
      shells using Nuclear Magnetic Resonance (NMR), Small Angle Neutron Scattering
      (SANS) and Quasi-Elastic Light Scattering (QELS). We have measured the adsorption
      of Bovine Serum Albumin (BSA) through Immunodiffusion methods, and found that it
      adsorbed in substantial amounts even when the distance between dextran chains at
      the core-diffuse shell interface is quite short. We have observed the aggregation
      of the nanoparticles induced by fibrinogen, and found that it was prevented when
      the density of dextran chains protruding from the core surface was sufficiently
      high. Finally we have measured the activation of the complement system by the
      nanoparticles, and found that it was also limited by the surface density of
      dextran chains that protrude from the core and by their mesh size within the
      diffuse shell.

PMID- 21093042
TI  - A bioactive self-assembled membrane to promote angiogenesis.
AB  - We report here on a bioactive hierarchically structured membrane formed by self
      assembly. The membrane is formed with hyaluronic acid and peptide amphiphiles
      with binding affinity for heparin, and its hierarchical structure contains both
      an amorphous zone and a layer of fibrils oriented perpendicular to the membrane
      plane. The design of bioactivity is based on the potential ability to bind and
      slowly release heparin-binding growth factors. Human mesenchymal stem cells
      (hMSCs) seeded on these membranes attached and remained viable. Basic fibroblast
      growth factor (FGF2) and vascular endothelial growth factor (VEGF) were
      incorporated within the membrane structure prior to self-assembly and released
      into media over a prolonged period of time (14 days). Using the chicken
      chorioallantoic membrane (CAM) assay, we also found that these membranes induced
      a significant and rapid enhancement of angiogenesis relative to controls.

PMID- 21093044
TI  - Quantitative proteomic profiling of breast cancers using a multiplexed
      microfluidic platform for immunohistochemistry and immunocytochemistry.
AB  - This paper describes a multiplexed microfluidic immunohistochemistry
      (IHC)/immunocytochemistry (ICC) platform for quantitative proteomic profiling in
      breast cancer samples. Proteomic profiling via ICC was examined for four breast
      cancer cell lines (AU-565, HCC70, MCF-7, and SK-BR-3). The microfluidic device
      enabled 20 ICC assays on a biological specimen at the same time and a 16-fold
      decrease in time consumption, and could be used to quantitatively compare the
      expression level of each biomarker. The immunohistochemical staining from the
      microfluidic system showed an accurate localization of protein and comparable
      quality to that of the conventional IHC method. Although AU-565 and SK-BR-3 cell
      lines were classified by luminal subtype and adenocarcinomas and were derived
      from the same patient, weak p63 expression was seen only in SK-BR-3. The HCC70
      cell line showed a triple-negative (estrogen receptor-negative/progesterone
      receptor-negative/human epidermal growth factor receptor 2-negative) phenotype
      and showed only cytokeratin 5 expression, a representative basal/myoepithelial
      cell marker. To demonstrate the applicability of the system to clinical samples
      for proteomic profiling, we were also able to apply this platform to human breast
      cancer tissue. This result indicates that the microfluidic IHC/ICC platform is
      useful for accurate histopathological diagnoses using numerous specific
      biomarkers simultaneously, facilitating the individualization of cancer therapy.

PMID- 21093045
TI  - Immobilization of selenocystamine on TiO2 surfaces for in situ catalytic
      generation of nitric oxide and potential application in intravascular stents.
AB  - Immobilization of selenocystamine on TiO(2) film deposited on silicon wafer and
      316 stainless steel stents for catalytic generation of nitric oxide was
      described. Polydopamine was used as the linker for immobilization of
      selenocystamine to the TiO(2) surface. In vitro stability of the immobilized
      selenocystamine was investigated and the result shows surface selenium loss
      occurs mostly in the first four weeks. The selenocystamine immobilized surface
      possesses glutathione peroxidase (GPx) activity, and the activity increases with
      the amount of grafted polydopamine. Such selenocystamine immobilized surfaces
      show the ability of catalytically decomposing endogenous S-nitrosothiols (RSNO),
      generating NO; thus the surface displays the ability to inhibit collagen-induced
      platelet acitivation and aggregation. Additionally, smooth muscle cells are
      inhibited from adhering to the selenocystamine immobilized sample when RSNO is
      added to the culture media. ELISA analysis reveals that cGMP in both platelets
      and smooth muscle cells significantly increases with NO release on
      selenocystamine immobilized samples. Two months in vivo results show that
      selenocystamine immobilized stents are endothelialized, and show significant anti
      proliferation properties, indicating that this is a favorable method for
      potential application in vascular stents.

PMID- 21093046
TI  - Co-electrospun dual scaffolding system with potential for muscle-tendon junction
      tissue engineering.
AB  - Tissue engineering has had successes developing single tissue types, but there is
      a need for methods that will allow development of composite tissues. For
      instance, muscle-tendon junctions (MTJ) require a seamless interface to allow
      force transfer from muscle to tendon. One challenge in engineering MTJs is
      designing a continuous scaffold suitable for both tissue types. We aimed to
      create a dual scaffold that exhibits regional mechanical property differences
      that mimic the trends seen in native MTJ. Poly(epsilon-caprolactone)/collagen and
      poly(l-lactide)/collagen were co-electrospun onto opposite ends of a mandrel to
      create a scaffold with 3 regions. Scaffolds were characterized with scanning
      electron microscopy, tensile testing (uniaxial, cyclic, and video strain), for
      cytocompatibility using MTS, and seeded with C2C12 myoblasts and NIH3T3
      fibroblasts. Native porcine diaphragm MTJs were also analyzed with video strain
      for comparison. Integrated scaffolds were created with fiber diameters from 452
      549 nm. Scaffolds exhibited regional variations in mechanical properties with
      moduli from 4.490-27.62 MPa and generally withstood cyclic testing, although with
      hysteresis. Video analysis showed scaffold strain profiles exhibited similar
      trends to native MTJ. The scaffolds were cytocompatible and accommodated cell
      attachment and myotube formation. The properties engineered into these scaffolds
      make them attractive candidates for tissue engineering of MTJs.

PMID- 21093047
TI  - In vitro generation of an osteochondral interface from mesenchymal stem cell
      collagen microspheres.
AB  - Creating biological interfaces between mechanically dissimilar tissues is a key
      challenge in complex tissue engineering. An osteochondral interface is essential
      in preventing mechanical failure and maintaining normal function of cartilage.
      Despite tremendous efforts in developing osteochondral plugs, formation of the
      osteochondral interface with proper zonal organization has not yet been reported.
      Here, we present a mesenchymal stem cell-collagen microsphere-based approach for
      complex tissue engineering and demonstrate in vitro formation of a stem cell
      derived osteochondral interface with calcified cartilage interface separating a
      non-calcified cartilage layer and an underlying bone layer. Cells at the
      interface region are hypertrophic chondrocytes while the extracellular matrix in
      this region contains collagen type II and X, calcium deposits and vertically
      running fibers. The simultaneous presence of appropriate medium and configuration
      during co-culture is necessary for the interface formation.

PMID- 21093048
TI  - Polyethylenimine-grafted copolymer of poly(l-lysine) and poly(ethylene glycol)
      for gene delivery.
AB  - A major challenge in gene therapy is the development of effective gene delivery
      vectors with low toxicity. In the present study, linear poly(ethylenimine) (lPEI)
      with low molecular weight was grafted onto the block copolymer (PPL) of poly(l
      lysine) (PLL) and poly(ethylene glycol)(PEG), yielding a ternary copolymer PEG-b
      PLL-g-lPEI (PPI) for gene delivery. In such molecular design, PLL, lPEI and PEG
      blocks were expected to render the vector biodegradability, proton buffering
      capacity, low cationic toxicity and potentially long circulation in vivo,
      respectively. Given proper control of molecular composition, the copolymers
      demonstrated lower cytotoxicity, proton buffering capacity, ability to condense
      pDNA and mediate effective gene transfection in various cell lines. With folate
      as an exemplary targeting ligand, the FA-PPI/pDNA complex showed much higher
      transgene activity than its nontargeting counterpart for both reporter and
      therapeutic genes in folate receptor(FR)-positive cells. FA-PPI mediated
      effective transfection of the TNF-related apoptosis-inducing ligand gene (TRAIL)
      in human hepatoma Bel 7402 cells, leading to cell apoptosis and great suppression
      of cell viability. Our results indicate that the copolymers might be a promising
      vector combining low cytotoxicity, biodegradability, and high gene transfection
      efficiency.

PMID- 21093049
TI  - Non-trophoblastic tumor of the placenta with combined histologic features of
      chorangioma and leiomyoma.
AB  - Chorangioma is the most common non-trophoblastic tumor of the placenta, which
      represents an excessive vascular proliferation within chorionic villi. While the
      histologic picture of a chorangioma may vary greatly from lesion to lesion, the
      presence of abundant smooth muscle tissue within a chorangioma has not been
      previously reported. Herein we report a case of a 34-year-old primigravida woman
      with a peculiar mesenchymal placental tumor, characterized by combined features
      of chorangioma and leiomyoma; large lobules of numerous small blood vessels
      within loose stroma, separated by broad bundles of smooth muscle fibers. Genetic
      studies by means of PCR excluded maternal and confirmed placental origin of the
      lesion.

PMID- 21093050
TI  - Caloxin 1b3: a novel plasma membrane Ca(2+)-pump isoform 1 selective inhibitor
      that increases cytosolic Ca(2+) in endothelial cells.
AB  - The purpose of this study was to invent an extracellular inhibitor selective for
      the plasma membrane Ca(2+) pump(s) (PMCA) isoform 1. PMCA extrude Ca(2+) from
      cells during signalling and homeostasis. PMCA isoforms are encoded by 4 genes
      (PMCA1-4). Pig coronary artery endothelium and smooth muscle express the genes
      PMCA1 and 4. We showed that the endothelial cells contained mostly PMCA1 protein
      while smooth muscle cells had mostly PMCA4. A random peptide phage display
      library was screened for binding to synthetic extracellular domain 1 of PMCA1.
      The selected phage population was screened further by affinity chromatography
      using PMCA from rabbit duodenal mucosa which expressed mostly PMCA1. The peptide
      displayed by the selected phage was termed caloxin 1b3. Caloxin 1b3 inhibited
      PMCA Ca(2+)-Mg(2+)-ATPase in the rabbit duodenal mucosa (PMCA1) with a greater
      affinity (inhibition constant=17+/-2 MUM) than the PMCA in the human erythrocyte
      ghosts (PMCA4, inhibition constant=45+/-4 MUM). The affinity of caloxin 1b3 was
      also higher for PMCA1 than for PMCA2 and 3 indicating its selectivity for PMCA1.
      Consistent with an inhibition of PMCA1, caloxin 1b3 addition to the medium
      increased cytosolic Ca(2+) concentration in endothelial cells. Caloxin 1b3 is the
      first known PMCA1 selective inhibitor. We anticipate caloxin 1b3 to aid in
      understanding PMCA physiology in endothelium and other tissues.

PMID- 21093052
TI  - Rapid reversal of quadraparesis in chronic eosinophilic leukaemia expressing the
      FIP1L1-PDGFRA transcript after therapy with imatinib.

PMID- 21093051
TI  - CD49d is an independent prognostic marker that is associated with CXCR4
      expression in CLL.
AB  - The world of chronic lymphocytic leukemia (CLL) research is awash with prognostic
      markers. However, very few of the current group play a clearly defined role in
      the pathology of this disease and even fewer represent a tractable therapeutic
      target. One such marker that fulfils both of these criteria is the integrin
      CD49d. This molecule been implicated in the capacity of CLL cells to migrate into
      lymphoid tissues and there is a CD49d blocking antibody, Natalizumab, currently
      in clinical trials. Here we carried out the largest multi-centre evaluation of
      CD49d as a prognostic marker in 652 primary CLL samples. We confirm that CD49d is
      predictive for time to first treatment (P<0.0001) and overall survival (P<0.0001)
      and increases the prognostic power of CD38, ZAP-70 and IGHV gene mutation status
      in concordant cases. Furthermore, CD49d retained independent prognostic
      significance in multivariate analysis. In contrast to previous studies, we showed
      no correlation between CD49d expression and in vitro resistance to fludarabine in
      liquid cultures (P=0.28) but CD49d(hi) cells were significantly more resistant
      than CD49d(lo) cells when assays were carried out on fibronectin-coated plates
      (P=0.03). Furthermore, we showed for the first time that the expression of CD49d
      is strongly associated with expression of the chemokine receptor CXCR4 suggesting
      a co-ordinated role for these molecules in the trafficking of CLL cells to the
      lymphoid tissues. Taken together, our data support the introduction of CD49d into
      routine immunophenotyping panels for CLL and indicate that the therapeutic
      targeting of this molecule may prove useful in this disease.

PMID- 21093053
TI  - Sorafenib for refractory FMS-like tyrosine kinase receptor-3 (FLT3/ITD+) acute
      myeloid leukemia after allogenic stem cell transplantation.

PMID- 21093054
TI  - Differential liver proteome mapping of control and cadmium-fed rats.
AB  - A comparative study of proteome maps from control and Cd-exposed rat liver was
      performed using a new technology of two-dimensional liquid chromatography
      separation method (PF-2D system, Beckman Coulter). Rats were fed for one month 0
      or 100 MUg Cd g(-1). The between-replicate and between-sample variations showed
      good repeatability and suitable reproducibility for the two dimensions of
      separation of proteins. In this complex mixture, PF-2D led to the separation of
      two major peaks which differed between control and Cd-exposed rat livers, one
      being identified by mass spectrometry as Cu/Zn superoxide dismutase (SOD), a well
      known biomarker of Cd exposure, the other as phosphatidylethanolamine binding
      protein (PEBP). SOD content was decreased in Cd-exposed rat liver, compared to
      the control group which was corroborated by a significant decrease of SOD
      activity. PEBP content also tended to be decreased after Cd exposure. Present
      results demonstrate interest but also limitations of proteomic approach using PF
      2D system to analyze effects of chemicals on organisms.

PMID- 21093055
TI  - Acute toxicity and biodegradability of N-alkyl-N-methylmorpholinium and N-alkyl
      DABCO based ionic liquids.
AB  - N-alkyl-N-methylmorpholinium and N-alkyl substituted 1,4
      diazabicyclo[2.2.2]octane (DABCO) based ionic liquids (ILs), N-alkyl-DABCO,
      bearing short alkyl chains are characterised by a low toxicity to Vibrio
      fischeri, although toxicity significantly increases on increasing the alkyl chain
      length. Alkyl chain length affects also biodegradability in the 28 days tests;
      the higher level of biodegradation was found in both the series in the case of
      the ethyl (C2) derivatives. In the case of N-ethyl DABCO based IL, although
      biodegradability is still around 40%, and consequently this IL cannot be
      classified as "readily biodegradable", this value is similar to the more
      biodegradable functionalized imidazolium based ILs.

PMID- 21093056
TI  - Characterization and expression of HLysG2, a basic goose-type lysozyme from the
      human eye and testis.
AB  - Lysozyme plays an important role in human innate immunity by causing bacterial
      cell lysis. We describe for the first time, the actual performance of human
      lysozyme g-like 2 (HLysG2), a mammalian g-type lysozyme. RT-PCR revealed that the
      HLysG2 gene was transcribed in eye and testis tissues. A spot was detected from
      human tears using 2D gel electrophoresis and was identified as HLysG2 using MALDI
      TOF/TOF MS and a MASCOT search with a matching score of 140 and 27% sequence
      coverage of the whole amino acid sequence. To gain insight into the in vitro
      antimicrobial activities of HLysG2, the mature peptide-coding region was cloned
      into Pichia pastoris for heterogeneous expression. Recombinant HLysG2, had an
      optimal at pH 6.0 and 30  degrees C, reached the peak activity of 1.2 * 10(4)U/mg
      at the sodium ion concentration of 75 mM and showed a higher salt tolerance than
      human c-type lysozyme (HLysC). Recombinant HlysG2 inhibited Gram-positive
      bacterial growth and did not inhibit Gram-negative bacterial and Candida albicans
      growth. Results indicated that HLysG2 is a potent antibacterial protein that may
      play a role in the innate immunity of the human eye.

PMID- 21093058
TI  - Personal and family history of suicidal behaviour is associated with lower
      peripheral cortisol in depressed outpatients.
AB  - BACKGROUND: Suicidal behaviour aggregates in families and HPA-axis dysregulation
      may help explain part of this familial aggregation. Nevertheless, exogenous
      manipulation of the HPA-axis has yielded mixed results. Naturalistic and non
      pharmacological inductions of the HPA-axis do not suggest hyper-responsiveness,
      yet suggest greater cognitive consequences of stress in individuals at risk for
      suicide. In this study, we aimed to characterize the relationship between plasma
      cortisol and an increased risk for suicide, as defined by family history. METHOD:
      Patients (N=148) with depressive disorders underwent psychopathological
      assessment, including structured investigation of past suicidal behaviour and
      underwent laboratory blood testing of cortisol. They also completed a family
      history interview investigating family psychopathology and suicidal behaviour,
      representing data on 848 first degree relatives. The relationship between plasma
      cortisol, past suicidal behaviour and suicidal behaviour among first degree
      relatives was examined. RESULTS: Lower levels of plasma cortisol were associated
      with a personal and family history of suicidal behaviour, as well as a family
      history of depression among first degree relatives. Multivariate analyses
      controlling for significant psychopathology replicated the association between
      lower levels of plasma cortisol, a family history of suicidal behaviour and
      personal history of suicide attempts, but not a family history of depression.
      Controlling for personal history of suicide attempts revealed an independent
      association between plasma cortisol and family history of suicidal behaviour,
      with an additional contribution by family history of depression in predicting the
      latter. CONCLUSIONS: Lower plasma cortisol is associated with a family history of
      suicide among depressed outpatients, independent of psychopathology and previous
      suicide attempts.

PMID- 21093059
TI  - Misdiagnosing bipolar disorder--do clinicians show heuristic biases?
AB  - BACKGROUND: Bipolar disorders (BD) are often misdiagnosed. Clinicians seem to use
      heuristics instead of following the recommendations of diagnostic manuals.
      Bruchmuller and Meyer (2009) suggest that 'reduced sleep' is a prototypic
      criterion that increases the likelihood of a bipolar diagnosis. This study
      examines if this criterion specifically elevates the likelihood of a bipolar
      diagnosis or if the finding of the study mentioned above is rather due to the
      total number of criteria. Furthermore, we want to replicate the finding that
      patients offering a causal explanation for their manic symptoms are misdiagnosed
      more often. Additionally, we examine therapeutic attributes that might influence
      diagnostic decisions as well as treatment consequences following a (mis
      )diagnosis. METHODS: 204 Psychotherapists were presented with a case vignette
      describing someone with a BD and were asked to make a diagnosis. Symptoms and the
      total number of criteria varied systematically within the vignettes but each
      still fulfilled enough diagnostic criteria to be diagnosed as bipolar. RESULTS:
      Almost 60% of the clinicians made misdiagnoses. A correct diagnosis did not
      depend on the specific criterion of 'reduced sleep' but on the total number of
      criteria. The causal explanation as well as therapeutic attributes did not
      significantly influence diagnostic decisions. However, the study showed that a
      misdiagnosis can lead to severe consequences concerning the treatment recommended
      by clinicians. LIMITATIONS: The validity of case vignettes is discussible.
      CONCLUSIONS: It seems as if specific symptoms might not be of so much relevance
      as assumed. Instead, clinicians seem to follow the additive model when making
      diagnoses.

PMID- 21093057
TI  - Altered IgE epitope presentation: A model for hypoallergenic activity revealed
      for Bet v 1 trimer.
AB  - In order to reduce side effects in the course of allergen specific immunotherapy
      hypoallergenic allergen derivatives with reduced IgE reactivity have been made by
      genetic engineering. In contrast to other recombinant hypoallergenic allergen
      derivatives which showed reduced IgE reactivity, a recombinant trimer of the
      major birch pollen allergen Bet v 1 showed reduced allergenic activity despite
      preserved IgE reactivity. We studied rBet v 1 trimer by SDS-PAGE, mass
      spectrometry, circular dichroism and gel filtration. Furthermore we investigated
      IgE and IgG reactivity of the rBet v 1 trimer in solid and liquid phase assays
      and compared its allergenic activity with that of rBet v 1 wildtype using
      basophil activation assays. In solid phase immunoassays rBet v 1 trimer exhibited
      even stronger IgE reactivity than the rBet v 1 wildtype, whereas both proteins
      were equally well recognized by Bet v 1-specific IgG antibody probes. In fluid
      phase IgE experiments rBet v 1 trimer inhibited IgE reactivity to rBet v 1
      wildtype but showed a more than 10-fold reduced allergenic activity compared to
      the rBet v 1 monomer. By analytical gel filtration it was demonstrated that,
      despite its monomeric appearance in SDS-PAGE the trimer occurred in fluid phase
      in the form of defined high molecular weight (>600 kDa) aggregates whereas rBet v
      1 wildtype strictly appeared as monomeric protein. The results indicate that the
      hypoallergenic nature of the rBet v 1 trimer is due to formation of defined high
      molecular weight aggregates which may be responsible for an altered presentation
      of IgE epitopes in a form with reduced capacity to crosslink effector-cell bound
      IgE. We thus provide evidence for a novel mechanism for hypoallergenic activity.

PMID- 21093060
TI  - Age predicts low-frequency transcranial magnetic stimulation efficacy in major
      depression.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) effectiveness in major
      depression has so far been studied mainly with high-frequency (>1 Hz)
      administration (HF-TMS). However, some available studies with low-frequency TMS
      (LF-TMS) have provided similar response rates to HF-TMS with better tolerance,
      but the evidence is mixed and controversial. METHODS: Randomized, controlled, two
      arm, clinical trial. 34 Major Depression patients were randomly assigned to
      receive 20 sessions of real or sham TMS of the right dorsolateral prefrontal
      cortex as adjuvant treatment to pharmacotherapy. The main stimulation parameters
      were 20 trains at 110% of the motor threshold for 60 s at a frequency of 1 Hz.
      Blinded external evaluators administered the Hamilton Depression Rating Scale.
      RESULTS: Both treatment groups significantly improved, although there were no
      statistical differences between them. In the real TMS group patients age
      inversely correlated with improvement of depressive symptoms at the end of the
      study (r=-0683 p=0.002). The percentage of decrease in scores on the Hamilton
      Scale was greater in subjects younger than 45 years old vs. others (41.3 +/- 22.6
      vs. 15.1 +/- 15.8; t=2.8 df=16, p=0.011). These real TMS subgroups did not differ
      significantly in their history of previous depressive disorders, or in the
      refractoriness indicators of the current episode. LIMITATIONS: Small size and
      highly refractory sample. CONCLUSION: Only younger patients benefited from LF
      rTMS as adjuvant treatment to antidepressants in this study.

PMID- 21093061
TI  - The distressed (Type D) personality in both patients and partners enhances the
      risk of emotional distress in patients with an implantable cardioverter
      defibrillator.
AB  - BACKGROUND: A subgroup of patients with an implantable cardioverter defibrillator
      (ICD) experiences emotional distress. This may be related to partner factors. We
      examined the impact of the personality of the partner (i.e., the distressed (Type
      D) personality) in combination with that of the patient on anxiety and depression
      levels in ICD patients. METHODS: Consecutively implanted ICD patients (N=281;
      80.1% men; mean age=58.3+/-11.0) and their partners (N=281; 20.6% men; mean
      age=56.5+/-11.7) completed the Type D Scale at baseline; patients also completed
      the Hospital Anxiety and Depression Scale at baseline and 6 months post
      implantation. RESULTS: ANOVA for repeated measures, using the Type D main effects
      and the interaction effect, showed that the interaction time by Type D patient by
      Type D partner was significant (F((1,277))=7.0, p=.009) for depression as
      outcome, but not for anxiety (F((1,277))=3.1, p=.08). Post-hoc comparisons
      revealed that Type D patients with a Type D partner (n=23/281, 8.2%) experienced
      the highest depression levels compared to other personality combinations (all
      ps<.05). LIMITATIONS: The group of Type D patients with a Type D partner was
      rather small. CONCLUSIONS: ICD patients with a Type D personality report more
      depressive symptoms, but not anxiety, if the partner also has a Type D
      personality. This may be due to poor communication and lack of emotional support
      in the relationship. These results emphasize the importance of taking into
      account the psychological profile of the partner in the management and care of
      the ICD patient, and to direct behavioural support not only at the ICD patient
      but also at the partner.

PMID- 21093062
TI  - Psychotherapies for comorbid anxiety in bipolar spectrum disorders.
AB  - BACKGROUND: Comorbid anxiety disorders are highly prevalent in bipolar disorder
      and have been shown to have serious negative impacts on the course of illness.
      The pharmacological treatment of anxiety can interact with the bipolar disorder
      and has not been proven effective. As such, many have recommended the
      psychological treatment of anxiety. This paper reviews the literature on
      psychological treatments for anxiety comorbid to bipolar disorder. METHOD: The
      Medline, PsychInfo and Web of Science databases were thoroughly examined for
      relevant treatment studies. RESULTS: Despite frequent recommendations in the
      literature, surprisingly few have studied the psychological treatment of comorbid
      anxiety in bipolar disorders. Nevertheless, preliminary results suggest that
      comorbid anxiety disorders can be effectively treated in a bipolar clientele
      using cognitive-behavioral therapy, mindfulness-based cognitive-behavioral
      therapy or relaxation training. In contrast, interpersonal, family therapy and
      psychoeducation alone would not seem to be beneficial treatment alternatives for
      anxiety. Cognitive-behavioral therapy appears to reduce the symptoms of obsessive
      compulsive disorder, generalized anxiety disorder, panic disorder, post-traumatic
      stress disorder and general symptoms of anxiety among patients with bipolar
      disorder. However, the long-term maintenance of anxiety treatment effects may be
      somewhat reduced and adaptations may be called for to augment and sustain
      benefits. CONCLUSIONS: There is an urgent need for randomized controlled trials
      of different forms of psychotherapy for anxiety disorders comorbid to bipolar
      disorder. Until such trials are available, the most promising approach would
      appear to be the sequential or modular CBT-based treatment of the anxiety
      disorder.

PMID- 21093063
TI  - Genetic polymorphisms of glutathione S-transferases GSTM1, GSTT1, GSTP1 and GSTA1
      as risk factors for schizophrenia.
AB  - Oxidative damage is thought to play a role in the predisposition to
      schizophrenia. We determined if the polymorphisms of the GSTP1, GSTM1, GSTT1 and
      GSTA1 genes, which affect the activity of these enzymes against oxidative stress,
      have a role as susceptibility genes for schizophrenia, analyzing 138
      schizophrenic patients and 133 healthy controls. We found that the combination of
      the absence of GSTM1 gene with the of the GSTM1 gene with the polymorphism
      GSTA1*B/*B, and the presence of the GSTT1 gene, represents a risk factor for
      schizophrenia, indicating that the combination of different GST polymorphisms has
      a role in the predisposition to schizophrenia, probably affecting the capacity of
      the cell to detoxify the oxidized metabolites of catecholamines.

PMID- 21093064
TI  - Idiopathic inflammatory myopathies.
AB  - The idiopathic inflammatory myopathies (IIM) encompass a heterogeneous group of
      rare disorders that present with acute, subacute, or chronic muscle weakness.
      Besides overlapping clinical manifestations, polymyositis, dermatomyositis and
      autoimmune necrotizing myopathy may be associated with cancer or collagen
      vascular disease, and respond generally well to immunosuppressive therapy.
      However, these 3 IIM are divergent from the histopathological and pathogenetic
      standpoints. On the other hand, inclusion body myositis (IBM), the most common
      IIM in the elderly, is clinically, histopathologically and pathogenetically
      distinct. IBM is also refractory to all currently available therapies. In this
      manuscript, we depict advances in our knowledge of the IIM, with emphasis on
      clinical presentation, associated conditions, laboratory features,
      electrophysiology, muscle histopathology, pathogenesis, and therapy.

PMID- 21093065
TI  - Does rapid maxillary expansion increase nasopharyngeal space and improve nasal
      airway resistance?
AB  - OBJECTIVE: To evaluate the effect of rapid maxillary expansion (RME) on the
      dimension of the nasopharyngeal space and its relation to nasal airway
      resistance. METHODS: Twenty-five school-age children (from 7 to 10 year-old) with
      mouth and/or mixed breathing, with mixed dentition and uni- or bilateral
      posterior crossbite involving the deciduous canines and the first permanent
      molars, were evaluated. RME was placed and remained during 90 days.
      Rhinomanometry and orthodontic documentation were performed at four different
      times, i.e., before (T(1)), immediately after (T(2)), 90 days (T(3)) and 30
      months (T(4)) after RME. RESULTS: Differences in nasopharyngeal area and in nasal
      airway resistance were observed only 30 months after RME, and could be explained
      by facial growth, and not because of the orthodontic procedure. CONCLUSION: RME
      does not influence on nasopharyngeal area or nasal airway resistance in long-term
      evaluation.

PMID- 21093066
TI  - Prospective double blind randomized clinical trial comparing 75% versus 95%
      silver nitrate cauterization in the management of idiopathic childhood epistaxis.
AB  - OBJECTIVES/HYPOTHESIS:  PRIMARY OUTCOME MEASURE: to evaluate which concentration
      of silver nitrate cauterization was more efficacious in the management of
      idiopathic childhood epistaxis. SECONDARY OUTCOME MEASURES: to evaluate side
      effects and pain scores of the differing concentrations. STUDY DESIGN:
      Prospective double blind randomized clinical trial. PARTICIPANTS AND SETTING: All
      children 16 years of age or younger referred by the accident and emergency
      department or general practitioner, with recurrent idiopathic epistaxis, who met
      the inclusion criteria entered the trial. Patients were randomized to receive
      either the 75% or 95% silver nitrate cauterization. Patients were reviewed at two
      weeks and eight weeks post cauterization. Pain scores, side effects and success
      of each treatments were recorded at the follow up clinic. RESULTS: 101 patients
      completed the trial. 52 patients were randomized to receive the 95%
      concentration, and 49 patients were randomized to receive the 75% cauterization.
      In the 75% concentration group, 98% of patients had total resolution of their
      symptoms at the eight-week follow up. Mean pain scores in this group was 1 out of
      10. In the 95% group, 90% had total resolution of their symptoms at the eight
      week follow up. Mean pain scores in this group was 5 out of 10. There was a
      statistical difference in efficacy and pain scores (0.01 and 0.001). CONCLUSION:
      We would recommend the use of 75% silver nitrate cauterization in the management
      of childhood epistaxis, it appears to be more efficacious, has fewer side effects
      and is better tolerated.

PMID- 21093067
TI  - The phenotypic and genetic biofilm formation characteristics of coagulase
      negative staphylococci isolates in children with otitis media.
AB  - OBJECTIVE: Medical biofilms are involved in a number of chronic infections
      including otitis media with effusion and chronic rhinosinusitis, which are common
      pediatric infectious diseases. The purpose of the study was to analyze the
      phenotypic and genotypic indicators of biofilm formation of coagulase negative
      staphylococci isolates in children with otitis media with effusion, and in
      children with chronic rhinosinusitis as a comparison group by using three
      different detection methods. METHODS: Forty nine children aged from 2 to 6 years
      old, diagnosed with otitis media with effusion were enrolled to the study. The
      comparative group consisted of twenty three strains of coagulase-negative
      staphylococci from the strains collection isolated from nose swabs from children
      3 to 7 years old suffering from rhinosinusitis for longer than 12 weeks. Cultured
      strains were tested for biofilm formation ability with three tests: Congo red
      agar, tissue culture plate methods and detection of ica operon. RESULTS: Out of
      97 ear effusion specimens, obtained from 49 children suffering from OME, 38 were
      found positive in conventional culture resulting in isolation of 50 different
      bacterial species. Nested-PCR method confirmed bacterial presence in 95 (97.9%)
      cases. Among 50 different bacterial species isolated, 30 (30.9%) CNS and 20
      (20.6%) other than CNS species. Detection of slime producing phenotype of CNS was
      performed with CRA plate test. Among OME isolates, 11 (36.7%) were CRA plate test
      positive. In case of isolates from CRS, 8 (34.8%) strains revealed black
      coloration on CRA. Using TCP method, strong adherence to microtiter plate was
      observed in two Staphylococcus epidermidis strains from OME and two S.
      epidermidis from CRS. By using the ica operon test, the genotypic ability to form
      biofilm was identified in 7 (23.3%) S. epidermidis strains cultured from ears
      effusion and in 3 (13%) strains from nose swabs. CONCLUSIONS: CNS strains
      revealed genotypic and phenotypic features responsible for the ability to form
      the biofilm in vivo. The presence of ica genes and phenotypic ability to form a
      biofilm by CNS strains emphasizes the pathogenic character of these strains in
      some cases of otitis media with effusion.

PMID- 21093069
TI  - Evaluation of the effectiveness of a phonoaudiology program for the
      rehabilitation of dysphagia in the elderly.
AB  - The object of this study was to evaluate the effectiveness of a phonoaudiology
      rehabilitation program directed towards the degenerative changes of the
      neurophysiological mechanisms responsible for the upper digestive system
      compromised by the age between 80 and 90 years, in a regime of internment in a
      long permanence institution in the city of Rio de Janeiro, which express, bodily,
      their difficulty in swallowing food of liquid or pasty consistency. To achieve
      such an object, the current study was developed in an experimental format or
      design, comprised of a sample group of 23 elderly subjects, of both genders,
      undergoing evaluation by the phonoaudiology protocol for evaluating the risk of
      dysphagia (abbreviated from the Portuguese name: Protocolo de Avaliacao do Risco
      para Disfagia=PARD), pre- and post-intervention procedure. The developed program
      used the indirect therapy approach based on the adaptive myotherapeutic and
      myofunctional stimulation, contemplating two isometric and isokinetic orofacial
      active myotherapeutic exercises, two passive myotherapeutic manipulations for the
      supra-hyoidal musculature, as well as adaptive cephalic postural maneuvres,
      associated to the intra-oral olfactive and gustative sensory stimulation. The
      evolution of the individuals was analyzed before and after the therapy by
      estimating the capacity of swallowing food in the liquid fluid (LF) consistency,
      by the paired Student t-test, giving a p=0.01, making the difference of 2.31
      between the 2 evaluations statistically significant. The changes produced by the
      PARD program in the capacity of individuals in swallowing food of a pasty
      consistency were also significant when analyzing the variance of the results on
      the 2 instances by using the F-test (pre- and post-intervention difference=4.47,
      p=0.039).

PMID- 21093070
TI  - The effect of loneliness and change in loneliness on self-rated health (SRH): a
      longitudinal study among aging people.
AB  - The association between adverse health and loneliness among aging people is
      known, but most of the studies are cross-sectional. In addition, the associations
      between changes in loneliness with health are less well known, especially in the
      case of aging people. The present study examined whether absence of loneliness in
      2005 predicted subsequent good SRH in 2008, and whether changes in loneliness
      were associated with SRH in 2008. Longitudinal, questionnaire-based data were
      collected from three age cohorts (born in 1926-30, 1936-40, and 1946-50) living
      in southern Finland. Baseline data was collected in 2002 (n = 2815, 66%); the
      follow-ups were done in 2005 (n = 2476, 60%) and 2008 (n =2 064, 73%). Logistic
      regression analyses were used to derive the results. Never or seldom experiencing
      loneliness was a strong predictor for good SRH. In addition, good health was
      common among those who never felt lonely. Among men the group experiencing
      decreasing loneliness had the highest OR of good health. Thus, loneliness is a
      significant contributor to poor SRH among aging people. In addition, favorable
      SRH is indicated not only by the absence of loneliness at both measurement
      points, but also by decreased loneliness. Preventing loneliness is important for
      health promotion.

PMID- 21093071
TI  - Atrial fibrillation (AF) and co-morbidity in elderly. A population based survey
      of 85 years old subjects.
AB  - The occurrence of AF increases sharply with age. The aim of this study was to
      explore and compare prevalent co-morbidity and self-estimated health-related
      quality of life (HRQoL) in subjects with AF versus subjects with sinus rhythm or
      pacemaker in 85 years old subjects. We analyzed data from a population of 336
      eighty-five years old subjects participating in the Elderly in Linkoping
      Screening Assessment (ELSA-85) study. Medical history was obtained from postal
      questionnaire, medical records and during medical examination that included a
      physical examination, cognitive tests, non-fasting venous blood samples and
      electrocardiographic (ECG) examination. 19% had an ECG showing AF. There were
      very few significant differences regarding medical history, self-estimated
      quality of life (QoL), laboratory- and examination findings and use of public
      health care between the AF group and the non-AF group. The study showed that the
      population of 85 years old subjects with AF was surprisingly healthy in terms of
      prevalent co-existing medical conditions, healthcare contacts and overall HRQoL.
      We conclude that elderly patients with AF do not in general have increased co
      morbidity than subjects without AF.

PMID- 21093072
TI  - Safety and efficacy of prasugrel compared with clopidogrel in different regions
      of the world.
AB  - BACKGROUND: Among patients with acute coronary syndrome (ACS), demographics,
      procedural characteristics and adjunctive medications differ globally. We
      examined whether there were differential effects of prasugrel compared with
      clopidogrel in the multinational TRITON-TIMI 38 study. METHODS: We divided the
      enrollment into 5 pre-specified geographic regions. Patients were randomized to
      prasugrel or clopidogrel without regard to country of enrollment. End points are
      expressed as Kaplan-Meier failure estimates through 15 months. Heterogeneity was
      evaluated using Cox proportional hazards model. Additional sensitivity analyses
      were performed by dividing countries into categories based on the Human
      Development Index (HDI), which is a composite measure of social and economic
      development. RESULTS: 13,608 patients were enrolled. Clinical characteristics
      including age, comorbidities, ACS presentation, stent types, and adjunctive
      medications differed broadly among regions. Despite these differences, no
      regional heterogeneity was observed with prasugrel compared to clopidogrel in the
      reduction of ischemic events (HR range: 0.76-0.87, p(interaction)>0.10 for each)
      and stent thrombosis (HR range: 0.34-0.72, p(interaction)>0.10 for each) or in
      the increased rate of non-CABG TIMI major bleeding (HR range: 1.16-1.76,
      p(interaction)>0.10 for each). There was a consistent trend in net clinical
      benefit (all cause death/MI/stroke/non-CABG TIMI major bleeding) favoring
      prasugrel (HR range: 0.81-0.97, p(interaction)>0.10 for each). Consistent results
      were also observed regarding the safety and efficacy of prasugrel compared with
      clopidogrel in both developed and developing countries. CONCLUSIONS: Despite
      differences in patient demographics, procedural techniques and adjunctive
      medications, consistent reduction in ischemic events and increased bleeding were
      seen with prasugrel compared with clopidogrel throughout the world.

PMID- 21093073
TI  - Prevalence and clinical impact of Upper Gastrointestinal Symptoms in subjects
      treated with low dose aspirin: the UGLA survey.
AB  - BACKGROUND: Upper Gastrointestinal Symtoms (UGS) is a reason for discontinuation
      in patients treated by Low Dose Aspirin (LDA). The nationwide UGLA survey was
      designed to evaluate the prevalence and the pattern of UGS in patients on LDA, to
      assess the independent correlates of UGS and finally to determine their impact on
      treatment compliance. METHODS: The UGLA survey was carried out on a
      representative sample of 10,000 subjects aged 50 or over. Prevalence and clinical
      impact of UGS related to LDA was appraised by standardised multi-choice
      questions. RESULTS: A total of 8106 propositus (8106/10,000) accepted to
      participate in the survey. Among them, 986 (12.2%) were treated with LDA. The
      prevalence of UGS was 15.4% in subjects on chronic LDA (152/986), 70% being
      gastroesophageal reflux (GER) (heartburn and/or regurgitation). UGS was reported
      to occur at least once a week in 60% of propositus (91/152) and daily life was
      reported to be moderately and severely impaired in 53% (81/152) and 20% (30/152)
      of them, respectively. UGS impacted compliance to treatment in 12% of propositus
      with UGS. A prior history of dyspeptic symptoms was predictive of LDA-related UGS
      (OR: 17.60; CI 95%: 11.52-26.88) whereas neither, gender nor aspirin dosage
      (ranging from 75 and 325 mg) predicted the occurrence of UGS. CONCLUSIONS:
      Fifteen percent of patients treated with LDA suffered UGS, mostly GER symptoms
      which had a negative impact on daily life in 3 out of 4 patients and on treatment
      compliance in 1 out of 8 patients.

PMID- 21093074
TI  - Can prolonged QTc and cTNT level predict the acute and long-term prognosis of
      stroke?
AB  - BACKGROUND: Previous studies in patients with stroke indicate that QTc
      prolongation and elevated cTNT are related to increased risk of all-cause and
      cardiovascular mortality. METHODS: We analysed the importance of
      electrocardiographic (ECG) abnormalities and elevated serum cardiac troponin
      (cTNT)--at baseline examination--as potential predictors for acute and long-term
      mortalities after stroke in a follow-up of 478 patients with a mean age of 78
      years. RESULTS: In a multivariate analysis, strong predictors for poor prognosis
      during the acute phase were: elevated cTNT (p=0.001); stroke severity (p=0.004);
      ischemia on ECG (p=0.044); and age (p=0.050). Prolonged QTc interval was on the
      limit to statistical significance (p=0.050) when using multivariate analysis,
      while clearly significant in a Cox-regression (when corrected for missing cTNT
      values). One year after stroke, when adjusted for covariates (gender, diabetes
      mellitus, hypertension, and ischemic heart disease), elevated cTNT (p=0.001),
      stroke severity (p=0.014), and age (p=0.031) retained a significant relation with
      mortality. Moreover, atrial fibrillation was strongly correlated with poor
      survival (p=0.009). Cox regression confirmed the predictive value of QTc, cTNT,
      age, and stroke severity, as markers of acute mortality in relation to stroke.
      CONCLUSION: Prolonged repolarization time independently predicts poor prognosis
      during the acute phase, but not one year after stroke. In the absence of acute
      myocardial infarction, elevated initial cTNT is strongly related to poor outcome,
      both during the acute phase and one year after stroke.

PMID- 21093075
TI  - Do currently recommended risk prediction tools help primary prevention of
      cardiovascular disease in Chinese population?

PMID- 21093076
TI  - Fluvastatin upregulates endothelial nitric oxide synthase activity via
      enhancement of its phosphorylation and expression and via an increase in
      tetrahydrobiopterin in vascular endothelial cells.
AB  - BACKGROUND: An HMG-CoA reductase inhibitor, fluvastatin, appears to act directly
      on the blood vessel wall to stabilize plaques in situ, agents that share this
      property have been termed vascular statins. METHODS: We investigated the effects
      of fluvastatin on endothelial nitric oxide synthase (eNOS) phosphorylation and
      expression, as well as terahydrobiopterin (BH4) metabolism, in human umbilical
      vein endothelial cells (HUVEC). RESULTS: Fluvastatin was observed to enhance eNOS
      phosphorylation at Ser-1177 and Ser-633 through the PI3-kinase/Akt and PKA
      pathways, respectively. Inhibition of eNOS phosphorylation using inhibitors of
      these pathways attenuated acute NO release in response to fluvastatin. The mRNA
      of GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme of the first step of de
      novo BH4 synthesis, as well as eNOS, was upregulated in HUVEC treated with
      fluvastatin. In parallel with this observation, fluvastatin increased
      intracellular BH4. Pre-treatment of HUVEC with the selective GTPCH inhibitor, 2,4
      diamino-6-hydroxypyrimidine, reduced intracellular BH4 and decreased citrulline
      formation following stimulation with ionomycin. Furthermore, the potentiating
      effect of fluvastatin was reduced by limiting the cellular availability of BH4.
      CONCLUSIONS: Our data demonstrate that fluvastatin phosphorylates and activates
      eNOS, and increases eNOS expression in vascular endothelial cells. In addition to
      modulating eNOS, fluvastatin potentiates GTPCH gene expression and BH4 synthesis,
      thereby increasing NO production and preventing relative shortages of BH4.

PMID- 21093077
TI  - Plasma amino-terminal propeptide of procollagen type III is associated with
      subclinical left ventricular systolic dysfunction in aortic stenosis.
AB  - OBJECTIVE: The aim of the study was to investigate the association of plasma
      amino-terminal propeptide of procollagen type III (PIIINP) with subclinical left
      ventricular (LV) systolic dysfunction in patients with aortic stenosis (AS) and
      normal LV ejection fraction. METHODS: The study was performed in 57 AS patients
      with normal LV ejection fraction and in 30 control subjects with normal aortic
      valve and normal LV ejection fraction. Tissue Doppler and speckle tracking image
      were performed to assess LV diastolic and systolic function. Plasma PIIINP level
      was measured by specific radioimmunoassay. RESULTS: In AS patients, LV systolic
      longitudinal strain was significantly reduced (-17.1 +/- 2.1 vs. -18.8 +/- 1.4%,
      P<0.001) and plasma PIIINP was increased compared with controls (2.5 +/- 0.6 vs.
      2.1 +/- 0.4 MUg/l, P<0.001). A significant correlation was found between LV
      systolic longitudinal strain and PIIINP (r=-0.67, P<0.001). In patients with
      abnormal LV diastolic function, LV systolic longitudinal strain was reduced
      compared with patients with normal LV diastolic function (-16.3 +/- 1.5 vs. -18.8
      +/- 2.1%, P<0.001) and plasma PIIINP was increased (2.8 +/- 0.5 vs. 2.0 +/- 0.3
      MUg/l, P<0.001). A stepwise multivariate regression analysis revealed that LV
      systolic longitudinal strain and diastolic blood pressure were independent
      predictors of plasma PIIINP (multiple r=0.71, P<0.001). CONCLUSIONS: Plasma
      PIIINP is associated with subclinical LV systolic dysfunction (the impaired LV
      systolic long axis function) in patients with AS and normal LV ejection fraction.
      In addition, the impaired LV systolic long axis function and increased plasma
      PIIINP concentration are most marked in patients with abnormal LV diastolic
      function.

PMID- 21093078
TI  - Reverse epidemiology reflects C-reactive protein as a bystander of
      atherosclerosis in established systemic inflammation models.

PMID- 21093079
TI  - ACTH deficiency and PGI(2) therapy in chronic thromboembolic pulmonary
      hypertension.

PMID- 21093080
TI  - Comparison of arrhythmia incidence after the extracardiac conduit versus the
      intracardiac lateral tunnel Fontan completion.

PMID- 21093081
TI  - Legacy of Avicenna and evidence-based medicine.
AB  - Although the term 'evidence-based medicine' (EBM) is of recent origin, its roots
      are generally agreed to lie in earlier times. Several writers have suggested that
      the 11th century CE physician and philosopher Avicenna (Ibn Sina) formulated an
      approach to EBM that broadly resembles modern-day principles and practice. The
      aim of this paper is to explore the origins and influence of Avicenna's version
      of EBM. A survey of the literature suggests that two influences on Avicenna's
      thought were crucial: the doctrine of Ijma; and Stoic logic, perhaps transmitted
      via the writings of Galen. In turn, Avicenna is known to have been a major
      influence on both medical practice and the development of logic in medieval
      Europe. Through this route, Avicennian logic (notably its inductive aspect)
      inspired the new style of thought associated with the scientific revolution,
      which later came to be reflected in 'scientific medicine', and may therefore have
      been an indirect source of EBM today.

PMID- 21093082
TI  - Acceptance and palatability for domestic and wildlife hosts of baits designed to
      deliver a tuberculosis vaccine to wild boar piglets.
AB  - Tuberculosis (TB) caused by Mycobacterium bovis, a member of the Mycobacterium
      tuberculosis complex, is an important health problem worldwide. The control of TB
      through vaccination of wildlife reservoirs may potentially have advantages over
      other management strategies. The most practical approach to deliver vaccines to
      wildlife is using oral baits that are stable under field conditions and effective
      in reaching the target species. Baits were developed in our laboratory to deliver
      oral vaccines to wild boar piglets. However, these baits were well accepted by
      other wild species. Therefore, bait consumption by different M. bovis hosts was
      evaluated herein. The results showed that the baits were well accepted by cattle,
      feral pigs, and adult red deer whereas small mammals like badgers and possums
      showed varying bait acceptance. Bait acceptance by different species has the
      advantage of targeting more than one wildlife reservoir when they coexist in the
      same area and need to be vaccinated for TB control. However, bait delivery
      methods such as the use of selective feeders to target the desired species should
      be developed to avoid bait consumption by other species.

PMID- 21093083
TI  - Longevity, genes and efforts: an optimal taxation approach to prevention.
AB  - This paper applies the analytical tools of optimal taxation theory to the design
      of the optimal subsidy on preventive behaviours, in an economy where longevity
      varies across agents, and depends on preventive expenditures and on longevity
      genes. Public intervention can be here justified on three grounds: corrections
      for misperceptions of the survival process and for externalities related to
      individual preventive behaviour, and redistribution across both earnings and
      genetic dimensions. The optimal subsidy on preventive expenditures is shown to
      depend on the combined impacts of misperception, externalities and self
      selection. It is generally optimal to subsidize preventive efforts to an extent
      depending on the degree of individual myopia, on how productivity and genes are
      correlated, and on the complementarity of genes and preventive efforts in the
      survival function.

PMID- 21093084
TI  - Accidental and deliberate microbiological contamination in the feed and food
      chains--how biotraceability may improve the response to bioterrorism.
AB  - A next frontier of the global food safety agenda has to consider a broad spectrum
      of bio-risks, such as accidental and intentional contaminations in the food and
      feed chain. In this article, the background for the research needs related to
      biotraceability and response to bioterrorism incidents are outlined. Given the
      current scale of international trade any response need to be considered in an
      international context. Biotraceability (e.g. the ability to use downstream
      information to point to processes or within a particular food chain that can be
      identified as the source of undesirable agents) is crucial in any food-born
      outbreak and particular in the response to bioterrorism events. In the later
      case, tested and proven biotraceability improves the following: (i) international
      collaboration of validated tracing tools and detection methods, (ii) multi
      disciplinary expertise and collaboration in the field of food microbiology and
      conceptual modeling of the food chain, (iii) sampling as a key step in biotracing
      (iv) optimized sample preparation procedures, including laboratory work in
      Biosafety level 3 (BSL-3) laboratories, (v) biomarker discovery for relevant
      tracing and tracking applications, and (vi) high-throughput sequencing using bio
      informatic platforms to speed up the characterization of the biological agent. By
      applying biotraceability, the response phase during a bioterrorism event may be
      shortened and is facilitated for tracing the origin of biological agent
      contamination.

PMID- 21093085
TI  - Efficiency of different sanitation methods on Listeria monocytogenes biofilms
      formed under various environmental conditions.
AB  - The resistance of Listeria monocytogenes biofilms formed under food processing
      conditions, against various sanitizing agents and disinfection procedures was
      evaluated in the present study. The first sanitation procedure included biofilm
      formation on stainless steel coupons (SS) placed in tryptic soy broth
      supplemented with 0.6% yeast extract (TSBYE) of various concentrations of NaCl
      (0.5, 7.5 and 9.5%) at different temperatures (5 and 20  degrees C). The biofilms
      formed were exposed to warm (60  degrees C) water for 20 min, or to peroxyacetic
      acid (2% PAA) for 1, 2, 3 and 6 min. Treatment with warm water caused no
      significant (P >= 0.05) reductions in the attached populations. Conversely,
      surviving bacteria on SS coupons decreased as the exposure time to 2% PAA
      increased and could not be detected by culture after 6 min of exposure. Biofilms
      formed at 20 degrees C were more resistant to PAA than biofilms formed at 5 
      degrees C. Salt concentration in the growth medium had no marked impact on the
      resistance to PAA. The second sanitation procedure included biofilm formation of
      nonadapted (NA) and acid-adapted (AA) cells in TSBYE of pH 5.0 and 7.0 (i.e., NA
      5.0, NA-7.0 and AA-5.0, AA-7.0) at 4  degrees C. Coupons bearing attached cells
      of L. monocytogenes were periodically exposed to chlorine (0.465% Cl(-)),
      quaternary ammonium compound (1% QAC) and 2% PAA. The resistance of attached
      cells to QAC, PAA and Cl(-) followed the order: AA-5.0>NA-7.0 >= AA-7.0>NA-5.0.
      The most effective sanitizer was QAC followed by PAA and Cl(-). The results can
      lead to the development of efficient sanitation strategies in order to eliminate
      L. monocytogenes from the processing environment. Furthermore, such results may
      explain the presence of L. monocytogenes after sanitation as a result of cell
      attachment history.

PMID- 21093086
TI  - A multiplex ligation detection assay for the characterization of Salmonella
      enterica strains.
AB  - A proof of principle of a multi-target assay for genotyping Salmonella has been
      developed targeting 62 genomic marker sequences of Salmonella related to
      pathogenicity. The assay is based on multiplex ligation detection reaction (LDR)
      followed by customized ArrayTube(r) microarray detection. The feasibility of the
      developed assay was verified in a method comparison study with conventional PCR
      using 16 Salmonella 'test' strains comprising eight serovars. Subsequently, the
      feasibility of the LDR microarray assay was also tested by analyzing 41 strains
      belonging to 23 serovars. With the exception of four serovars each serovar was
      characterized by a unique virulence associated gene repertoire. The LDR
      microarray platform proved to be a convenient, rapid and easy to use tool with
      potential in tracing a Salmonella contamination in the food chain, for outbreak
      studies, and to provide data for risk assessors that support bio-traceability
      models.

PMID- 21093087
TI  - Characterization of psychrotrophic bacterial communities in modified atmosphere
      packed meat with terminal restriction fragment length polymorphism.
AB  - Characterization of psychrotrophic lactic acid bacteria (LAB) and Brochothrix
      thermosphacta communities is needed to understand the microbial ecology of
      spoilage of modified atmosphere-packed (MAP) meats. To overcome the limitations
      of the currently used methods for the characterization of psychrotrophic
      bacterial communities in meat, we developed a culture-independent, 16S rRNA gene
      targeted terminal restriction fragment length polymorphism (T-RFLP) method. An
      identification library consisting of 100 Gram-positive and 30 Gram-negative meat
      associated bacterial strains was set up to identify the terminal restriction
      fragments derived from the communities. The taxonomic resolution level of the T
      RFLP method was in between genus and species within the investigated LAB strains
      and within family and genus within the investigated Gram-negative strains. The
      established library was applied to identify the members of bacterial communities
      in MAP minced meat at the end of the shelf life. The T-RFLP results and plate
      counts on Man-Rogosa-Sharpe, Violet Red Bile Glucose, and Streptomycin sulfate
      thallium acetate actidione agars indicated that LAB and B. thermosphacta
      predominated in meat. The bacterial taxa associated with the T-RFLP results were
      compared to those identified among plate-grown LAB isolates by numerical
      ribopattern analysis. Both methods agreed that Leuconostoc spp. and
      Carnobacterium spp. prevailed in the LAB community in minced meat followed by
      Lactobacillus algidus, Lactococcus spp. and Weissella spp. Colony identification
      revealed that Leuconostoc gasicomitatum, L. gelidum, Carnobacterium divergens and
      C. maltaromaticum were the predominant LAB species. The T-RFLP results were shown
      to correlate with viable counts of Leuconostoc spp. and B. thermosphacta. The T
      RFLP method was found to be a useful tool enabling rapid and high-throughput
      characterization of psychrotrophic bacteria prevailing in MAP meat.

PMID- 21093088
TI  - Effects of ozone exposure on the xerophilic fungus, Eurotium amstelodami IS-SAB
      01, isolated from naan bread.
AB  - Xerophilic moulds cause contamination and spoilage of low moisture foods. This
      study examined the effect of ozone fumigation on growth of a Eurotium species
      isolated from naan bread. Two ozone treatments were used - a low-level long-term
      exposure (0.4 MUmol/mol for 21 days) and high-level short-term exposure (300
      MUmol/mol for 5 to 120 min). For the low level exposure the combination of
      different media sucrose concentrations (0, 5, 10 and 20% w/v) with ozone
      treatment was also assessed. The growth of the isolate was found to be sensitive
      to low-level ozone fumigation depending on the media sucrose concentration and
      duration of the exposure. Low-level ozone exposure significantly (p<0.05) reduced
      the number of asexual spores formed in media with no added sucrose, an effect not
      observed in media with higher sucrose levels. Electron microscope observations of
      colonies indicated that ozone exposed cultures produced lower numbers of
      cleistothecia. High-level ozone exposure for short durations reduced spore
      viability although 100% reduction in viability was achieved only after 120 min
      exposure. This work demonstrates that ozone may be used to reduce spore
      production in Eurotium but that the ozone effect can be mediated by sucrose
      levels in the growth medium.

PMID- 21093089
TI  - A novel dipeptidyl peptidase IV inhibitor DA-1229 ameliorates streptozotocin
      induced diabetes by increasing beta-cell replication and neogenesis.
AB  - We studied the effect of a novel dipeptidyl peptidase IV (DPP IV) inhibitor, DA
      1229, on blood glucose profile and pancreatic beta-cell mass in established
      diabetes after streptozotocin (STZ) treatment. Mice that developed diabetes after
      administration of STZ 100mg/kg were treated with DA-1229 for 13 weeks. DA-1229
      significantly reduced plasma DPP IV activity, and enhanced glucagon-like peptide
      1 (GLP-1) levels. In STZ-treated mice fed DA-1229 (STZ-DA), blood glucose levels
      were significantly lower than those in diabetic mice fed normal chow (STZ-NC).
      Basal and glucose-stimulated insulin secretion and glucose tolerance assessed by
      intraperitoneal glucose tolerance test were significantly improved by DA-1229
      administration. Volume density of beta-cell was significantly increased in STZ-DA
      mice compared to STZ-NC mice, suggesting that DA-1229-mediated amelioration of
      established diabetes was due to beneficial effect of DA-1229 on beta-cell mass.
      The number of replicating beta-cells and that of scattered small beta-cell unit
      representing beta-cell neogenesis were significantly increased in STZ-DA mice
      compared to STZ-NC mice, explaining increased beta-cell mass by DA-1229. The
      expression of PDX-1, a downstream mediator of GLP-1 action, was increased in
      islets of STZ-DA mice compared to STZ-NC mice. These results suggest a
      therapeutic potential of DA-1229 in diabetes, particularly that associated with
      decreased beta-cell mass.

PMID- 21093091
TI  - Pathogenesis of cholestatic hepatitis C.

PMID- 21093090
TI  - Hedgehog signaling in the liver.
AB  - Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls
      progenitor cell fate and tissue construction during embryogenesis occurs during
      many types of liver injury in adult. The net effects of activating the Hedgehog
      pathway include expansion of liver progenitor populations to promote liver
      regeneration, but also hepatic accumulation of inflammatory cells, liver
      fibrogenesis, and vascular remodeling. All of these latter responses are known to
      be involved in the pathogenesis of cirrhosis. In addition, Hh signaling may play
      a role in primary liver cancers, such as cholangiocarcinoma and hepatocellular
      carcinoma. Study of Hedgehog signaling in liver cells is in its infancy.
      Additional research in this area is justified given growing experimental and
      clinical data supporting a role for the pathway in regulating outcomes of liver
      injury.

PMID- 21093093
TI  - Using "off-the-shelf" tools for terabyte-scale waveform recording in intensive
      care: computer system design, database description and lessons learned.
AB  - Until now, the creation of massive (long-term and multichannel) waveform
      databases in intensive care required an interdisciplinary team of clinicians,
      engineers and informaticians and, in most cases, also design-specific software
      and hardware development. Recently, several commercial software tools for
      waveform acquisition became available. Although commercial products and even
      turnkey systems are now being marketed as simple and effective, the performance
      of those solutions is not known. The additional expense upfront may be worthwhile
      if commercial software can eliminate the need for custom software and hardware
      systems and the associated investment in teams and development. We report the
      development of a computer system for long-term large-scale recording and storage
      of multichannel physiologic signals that was built using commercial solutions
      (software and hardware) and existing hospital IT infrastructure. Both numeric (1
      Hz) and waveform (62.5-500 Hz) data were captured from 24 SICU bedside monitors
      simultaneously and stored in a file-based vital sign data bank (VSDB) during one
      year period (total DB size is 4.21TB). In total, vital signs were recorded from
      1,175 critically ill patients. Up to six ECG leads, all other monitored
      waveforms, and all monitored numeric data were recorded in most of the cases. We
      describe the details of building blocks of our system, provide description of
      three datasets exported from our VSDB and compare the contents of our VSDB with
      other available waveform databases. Finally, we summarize lessons learned during
      recording, storage, and pre-processing of physiologic signals.

PMID- 21093092
TI  - Pegylated interferon alpha targets Wnt signaling by inducing nuclear export of
      beta-catenin.
AB  - BACKGROUND & AIMS: Pegylated-Interferon-alpha2a (peg-IFN), a first line therapy
      for Hepatitis C virus (HCV) patients, also impacts the recurrence of
      hepatocellular carcinoma (HCC). The activation of the Wnt pathway due to beta
      catenin gene mutations contributes to the development of a significant subset of
      HCC. Herein, we explored the effect of peg-IFN on Wnt/beta-catenin signaling in
      vitro and in vivo. METHODS: Multiple human hepatoma cell lines were treated with
      Peg-IFN to assess its effect on the Wnt pathway and the mechanisms involved.
      Transgenic (TG) mice expressing stable beta-catenin mutant in the liver were
      exposed to diethylnitrosamine (DEN) and treated with peg-IFN. RESULTS: In vitro,
      peg-IFN decreased the transcriptional activity of beta-catenin/Tcf and did so
      independently of JAK/Stat signaling. Peg-IFN treatment led to increased mRNA and
      protein expression of RanBP3, a known beta-catenin nuclear export factor, in all
      hepatoma cells. Co-precipitation studies showed an increased association between
      RanBP3 and beta-catenin after peg-IFN treatment. The siRNA-mediated RanBP3
      knockdown abrogated Peg-IFN-induced decrease in TOPFlash reporter activity. In
      vivo, Peg-IFN treatment led to increased nuclear RanBP3, decreased nuclear beta
      catenin and cyclin D1, and decreased cytoplasmic glutamine synthetase. Increased
      association of RanBP3 and beta-catenin was also observed in vivo in response to
      Peg-IFN that led to decreased hepatocyte proliferation. CONCLUSIONS: Peg-IFN
      inhibits beta-catenin signaling through the up-regulation of RanBP3, which may be
      a contributory mechanism for the delayed HCC and improved survival in treated HCV
      patients. This observation might have chemo-preventive or chemo-therapeutic
      implications in tumor with aberrant Wnt pathway activation.

PMID- 21093094
TI  - New CT response criteria in non-small cell lung cancer: proposal and application
      in EGFR tyrosine kinase inhibitor therapy.
AB  - We aimed to devise new CT response criteria (new response criteria, NRC) in
      patients with non-small cell lung cancer (NSCLC) and to evaluate the efficacy of
      the criteria for stratifying patient responses and predicting patient survival
      compared to that of the traditional size-based criteria RECIST version 1.1. Our
      institutional review board approved this study with a waiver of informed consent.
      We enrolled 80 NSCLC patients as an experimental arm and treated them with
      epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). Two
      blinded, independent radiologists assessed CT images for tumor response using the
      NRC, which were also validated in a separate arm (75 NSCLC patients). Tumor
      responses evaluated by RECIST 1.1 and the new criteria were compared from each
      other and correlated with patient survival. For statistical analyses, Kaplan
      Meier method and kappa statistics were used. In the experimental arm (n=80),
      interobserver agreements for the assessment of patient response were excellent
      for both RECIST and NRC. Sixteen RECIST nonresponding patients achieved a
      designation of partial response according to NRC. In the validation arm (n=75),
      patients of optimal response (partial response) with the new criteria had median
      overall survival of 18.4 months compared with 8.5 months in patients with poor
      response (P=.04). However, RECIST failed to show survival difference between the
      two response groups. In NSCLC patients treated with EGFR-TKIs, new CT criteria
      reflecting additional morphological characteristics of target lesions are
      reproducible and have statistically significant association with overall
      survival.

PMID- 21093095
TI  - Stoichiogenomics: the evolutionary ecology of macromolecular elemental
      composition.
AB  - The new field of 'stoichiogenomics' integrates evolution, ecology and
      bioinformatics to reveal surprising patterns of the differential usage of key
      elements [e.g. nitrogen (N)] in proteins and nucleic acids. Because the canonical
      amino acids as well as nucleotides differ in element counts, natural selection
      owing to limited element supplies might bias monomer usage to reduce element
      costs. For example, proteins that respond to N limitation in microbes use a lower
      proportion of N-rich amino acids, whereas proteome- and transcriptome-wide
      element contents differ significantly for plants as compared with animals,
      probably because of the differential severity of element limitations. In this
      review, we show that with these findings, new directions for future
      investigations are emerging, particularly via the increasing availability of
      diverse metagenomic and metatranscriptomic data sets.

PMID- 21093096
TI  - Redox-sensitive regulation of macrophage-inducible nitric oxide synthase
      expression in vitro does not correlate with the failure of apocynin to prevent
      lung inflammation induced by endotoxin.
AB  - Reactive oxygen and nitrogen species are among the crucial mediators in the
      development of the pathological inflammatory process in the lungs and contribute
      to the damage of lung epithelium. The aim of the present study was to evaluate
      the potential of selected antioxidants or inhibitors of NADPH oxidase
      (glutathione, N-acetyl cysteine, trolox, apocynin, and diphenyleneiodonium
      chloride) to modulate nitric oxide (NO) production and inducible nitric oxide
      synthase (iNOS) expression by mouse macrophages induced by lipopolysaccharide
      (LPS) in vitro and to evaluate the potential of apocynin to modulate the course
      of LPS-induced lung inflammation in vivo. All the tested drugs revealed
      inhibitory effects on LPS-induced NO production and iNOS expression in RAW 264.7
      macrophages. Further, apocynin significantly inhibited activation of nuclear
      factor kappa B induced by LPS. Ex vivo, diphenyleneiodonium chloride and apocynin
      significantly reduced ROS production by inflammatory cells isolated from
      bronchoalveolar lavage fluid. In contrast, in vivo intranasal application of
      apocynin did not exert any significant effect on the course of lung inflammation
      in mice induced by LPS that was evaluated based on the accumulation of cells,
      interleukine-6, interleukine-12, RANTES, tumor necrosis factor-alpha, and protein
      concentration in bronchoalveolar lavage fluid and expression of iNOS in lung
      tissue. Only effected were the levels of nitrites 36 h after induction of lung
      inflammation that were reduced in the apocynin-treated group. In conclusion, our
      data suggest that the inhibitors of NADPH oxidase possess inhibitory potential
      against LPS-induced NO production by mouse macrophages; however, apocynin failed
      to reduce LPS-induced lung inflammation in mice.

PMID- 21093097
TI  - IFN-alpha boosts epitope cross-presentation by dendritic cells via modulation of
      proteasome activity.
AB  - We have investigated the molecular mechanisms underlying the peculiar cross
      presentation efficiency of human dendritic cells (DCs) differentiated from
      monocytes in the presence of Granulocyte-Macrophage Colony-Stimulating Factor (GM
      CSF) and Interferon (IFN)-alpha (IFN-DCs). To this end, we evaluated the
      capability of IFN-DCs to present and cross-present epitopes derived from Epstein
      Barr Virus (EBV) or human melanoma-associated antigens after exposure to cell
      lysates or apoptotic cells. In an autologous setting, IFN-DCs loaded with
      Lymphoblastoid Cell Lines (LCL) lysates or apoptotic LCL were highly efficient in
      expanding, respectively, EBV-specific class II- or class I-restricted memory T
      cell responses. Of note, IFN-DCs loaded with apoptotic LCL were more potent than
      fully mature DCs in triggering the cytotoxicity of CD8(+) T lymphocytes
      recognizing a subdominant HLA-A*0201-restricted epitope derived from EBV latent
      membrane protein 2 (LMP2). In addition, IFN-DCs loaded with apoptotic human
      melanoma cells were highly efficient in cross-presenting the MART-1(27-35)
      epitope to a specific CD8(+) cytotoxic T cell clone, and this functional activity
      was proteasome-dependent. These IFN-DC properties were associated with an
      enhanced expression of all the immunoproteasome subunits as well as of TAP-1, TAP
      2 and tapasin, and, interestingly, to a higher proteasome proteolytic activity as
      compared to immature or mature DCs. Altogether, these results highlight new
      mechanisms by which IFN-alpha influences antigen processing and cross
      presentation ability of monocyte-derived DCs, with potentially important
      implications for the development of DC-based therapeutic vaccines.

PMID- 21093099
TI  - Role of Rab1b in COPII dynamics and function.
AB  - In eukaryotic cells, proteins destined for secretion are translocated into the
      endoplasmic reticulum (ER) and packaged into so-called COPII-coated vesicles. In
      the ER exit sites (ERES), COPII has the capacity of deforming the lipid bilayer,
      where it modulates the selective sorting and concentration of cargo proteins. In
      this study, we analyze the involvement of Rab1b in COPII dynamics and function by
      expressing either the Rab1b negative-mutant (Rab1N121I) or the Rab1b GTP
      restricted mutant (Rab1Q67L), or performing short interference RNA-based
      knockdown. We show that Rab1b interacts with the COPII components Sec23, Sec24
      and Sec31 and that Rab1b inhibition changes the COPII phenotype. FRAP assays
      reveal that Rab1b modulates COPII association/dissociation kinetics at the ERES
      interface. Furthermore, Rab1b inhibition delays cargo sorting at the ER exit
      sites. We postulate that Rab1b is a key regulatory component of COPII dynamics
      and function.

PMID- 21093098
TI  - S-Adenosylmethionine regulates connexins sub-types expressed by hepatocytes.
AB  - Intercellular communication via GAP Junctions plays an important role in tissue
      homeostasis, apoptosis, carcinogenesis, cell proliferation and differentiation.
      Hepatocyte connexins (Cx) 26 and 32 levels are decreased during the de
      differentiation process of primary hepatocytes in culture, a situation that is
      also characterized by a decrease in S-Adenosylmethionine (SAMe) levels. In this
      current study, we show that SAMe supplementation in cultured hepatocytes every
      12h, leads to an up-regulation of Cx26 and 32 mRNA and protein levels and blocks
      culture-induced Cx43 expression, although it failed to increase Cx26 and 32
      membrane localization and GAP junction intracellular communication. SAMe reduced
      nuclear beta-catenin accumulation, which is known to stimulate the TCF/LEF
      dependent gene transcription of Cx43. Moreover SAMe-induced reduction in Cx43 and
      beta-catenin was prevented by the proteasome inhibitor MG132, and was not
      mediated by GSK3 activity. SAMe, and its metabolite 5'-methylthioadenosine (MTA)
      increased Cx26 mRNA in a process partially mediated by Adenosine A(2A) receptors
      but independent of PKA. Finally livers from MAT1A knockout mice, characterized by
      low hepatic SAMe levels, express higher Cx43 and lower Cx26 and 32 protein levels
      than control mice. These results suggest that SAMe maintains a characteristic
      expression pattern of the different Cxs in hepatocytes by differentially
      regulating their levels.

PMID- 21093100
TI  - Identification of S-RNase and peroxidase in petunia nectar.
AB  - Previous SDS PAGE gel analysis of the floral nectars from petunia and tobacco
      plants revealed significant differences in the protein patterns. Petunia floral
      nectar was shown to contain a number of RNase activities by in gel RNase activity
      assay. To identify these proteins in more detail, the bands with RNase activity
      were excised from gel and subjected to trypsin digestion followed by LC-MS/MS
      analysis. This analysis revealed that S-RNases accumulate in nectar from Petunia
      hybrida, where they should carry out a biological function different from self
      pollen rejection. In addition, other proteins were identified by the LC-MS/MS
      analysis. These proteins include a peroxidase, an endochitinase, and a putative
      fructokinase. Each of these proteins contained a secretory signal sequence that
      marked them as potential nectar proteins. We developed RT-PCR assays for each of
      these five proteins and demonstrated that each of these proteins was expressed in
      the petunia floral nectary. A discussion of the role of these proteins in
      antimicrobial activity in nectar is presented.

PMID- 21093101
TI  - Significance of phenols in cadmium and nickel uptake.
AB  - The effects of 2-aminoindane-2-phosphonic acid (AIP), a potent phenylalanine
      ammonia-lyase (PAL) inhibitor, on the accumulation of cadmium and nickel in
      chamomile (Matricaria chamomilla) were examined in this study. In vitro assay of
      AIP effect showed a 90% reduction in PAL activity. In plants cultured for 7 days
      in Cd or Ni solutions with AIP, PAL activity was higher in both shoots and roots
      (in comparison with metals without AIP), and was correlated with changes in free
      phenylalanine content. Individual amino acids were both positively and negatively
      affected by AIP, with the accumulation of tyrosine and proline showing increases
      in some variants. Contents of soluble phenols and flavonoids were not
      considerably affected, while amounts of coumarin-related compounds, cell wall
      bound phenols and phenolic acids were substantially reduced in AIP-treated
      variants. Lignin accumulation decreased in controls and increased in Cd variants
      in response to AIP. Shoot Cd content was depleted, but shoot Ni was elevated by
      AIP. Total root content of Cd and Ni decreased in +AIP variants. AIP also caused
      more expressive changes in hydrogen peroxide and superoxide content in Cd than in
      Ni variants. Our results indicate that phenols have important roles in the uptake
      of Cd and Ni. The present findings are discussed in the context of available data
      regarding AIP's effect on phenols.

PMID- 21093102
TI  - [Using systemic corticotherapy for adult gonococcal keratoconjunctivitis: three
      case reports].
AB  - INTRODUCTION: adult gonococcal keratoconjunctivitis is a rare disease possibly
      leading to blindness, whose severity is related to the risk of corneal
      perforation and whose progression is conditioned by the rapidity of diagnosis and
      therapeutic management. PURPOSE: discuss the value of general corticotherapy in
      the treatment of scleritis associated with this disease. PATIENTS AND METHODS:
      retrospective analysis of patients with adult gonococcal keratoconjunctivitis
      managed in an emergency setting in 2007. OBSERVATION: three patients aged 22-55
      years contracted the disease during unprotected sexual activity. Involvement was
      bilateral in two cases out of three; the intensity of the signs was always
      asymmetrical. Each patient underwent stromal melting of the superior limbic
      structures, with severity proportional to the delay in treatment. For each case,
      systemic and local antibiotics did not control corneal thinning, which seemed
      correlated with the intensity of the systematically associated signs of scleral
      inflammation. Treatment of scleritis with general corticotherapy under antibiotic
      cover stabilized the corneal thickness. DISCUSSION: whether the physiopathology
      of perilimbic corneal thinning can lead to ocular perforation in this condition
      is unknown. In our experience, the stabilization of corneal thickness seems
      correlated with regression of the scleritis observed after introducing general
      corticotherapy, potentially indicating aseptic inflammatory involvement.
      CONCLUSION: stromal melting of the limbus observed in adult gonococcal
      keratoconjunctivitis seems to be related to the associated scleritis. Systemic
      corticotherapy controls progression and reduces the risk of corneal perforation.

PMID- 21093103
TI  - [Role of intolerance to hypoxia in the occurrence of anterior bilateral ischaemic
      optic neuropathy at high altitude].
AB  - The pathophysiology of nonarteritic anterior ischemic optic neuropathy (NA-AION)
      is still imperfectly understood, but arterial hypertension seems to play a
      decisive role. Intolerance to hypoxia is defined as desaturation of hemoglobin
      more than 15% at rest and/or elevation of blood pressure at rest or after
      exercise over 20mmHg in hypoxia. We report the case of a 66-year-old woman who
      presented bilateral NA-AION during a trek at high altitude (>2500m). The
      etiological check up was negative. Due to the circumstances of occurrence, we
      requested a tolerance to hypoxia test, which was positive. In this case, the
      combined effects of altitude and effort probably led to prolonged desaturation of
      oxyhemoglobin associated with an excessive blood pressure increase upon exercise
      leading to ischemia of the optic nerve head. This case showed the value of a
      systematic search for hypoxia tolerance in patients with nonarteritic anterior
      ischemic optic neuropathy occurring during a situation of prolonged hypoxia (long
      distance flight, high altitude).

PMID- 21093104
TI  - [Nutrition and age-related macular degeneration].
AB  - Age-related macular degeneration is a growing burden disease with a high
      prevalence in elderly: it is the first cause of blindness in developped
      countries. It is a multifactorial disease with genetic factors and nutritional
      factors. Carotenoids, lutein and zeaxanthin are components of macular pigment and
      they have a filter role for blue light and an antioxidant role. Other nutritional
      factors might play a role as antioxidants: zinc, selenium, vitamin E, vitamin
      C... which lead to the ARED Study. It is the only one study with proven positive
      effects on the disease progression (stages 3 and 4). A high glycemic index
      increases oxidative stress. Long chain omega-3 polyunsaturated fatty acids have a
      protective effect. Available data are presented and discussed. These are new
      preventive issues.

PMID- 21093105
TI  - [Advantages and limits of multiple grafts (third keratoplasty) under local
      cyclosporin 2%].
AB  - INTRODUCTION: iterative penetrating keratoplasty procedures (PKPs) increase the
      risk of graft rejection. Surgeons are reluctant to perform a third procedure
      following two previous graft failures. We evaluated the outcomes of patients who
      had three successive PKPs treated with a local combination of cyclosporin 2% A
      and dexamethasone 0.1% eye drops. PATIENTS AND METHODS: this is a retrospective
      study of a series of cases including 15 eyes of 15 patients treated and followed
      in the ophthalmology unit at the Hotel-Dieu Hospital in Paris (2006-2009).
      RESULTS: after an average follow-up of 20.5+/-2 months, the risk of transplant
      rejection was 13.33% and the duration of follow-up corresponded in all patients
      to the duration of treatment with cyclosporin eye drops. The treatment was not
      interrupted by any patient because of intolerance. CONCLUSION: in this study, we
      observed a success rate justifying the indication of the third keratoplasty under
      local cyclosporin 2% classically considered debatable.

PMID- 21093106
TI  - Cutaneous small-vessel vasculitis associated with solid organ malignancies: the
      Mayo Clinic experience, 1996 to 2009.
AB  - BACKGROUND: Although rare, cutaneous small-vessel vasculitis (CSVV) secondary to
      solid organ malignancy has been documented. OBJECTIVE: We sought to better
      understand the frequency, clinical course, therapeutic response, and outcome of
      CSVV associated with solid organ malignancy. METHODS: We conducted a
      retrospective chart review of patients seen between 1996 and 2009 with diagnoses
      of biopsy-proven cutaneous leukocytoclastic vasculitis and solid organ malignancy
      separated by less than 12 months. RESULTS: Of 17 patients (mean age, 66.5 years),
      10 patients (59%) were male. CSVV occurred before (3 patients; 18%), concurrent
      with (3 patients; 18%), and after (11 patients; 65%) diagnosis of solid organ
      malignancy. The most common solid organ malignancy was of the lung (n = 4; 24%).
      Other associated cancers were breast (n = 3); prostate (n = 2); colon (n = 2);
      renal (n = 2); thyroid (n = 1); bladder (n = 1); gallbladder (n = 1); and
      peritoneal (n = 1). Three patients had cutaneous vasculitis in association with
      malignancy recurrence despite having no cutaneous vasculitis associated with
      their primary malignancy. Vasculitis remission with use of immunosuppressive
      agents alone occurred in 9 patients (53%). Eleven patients (65%) were alive at
      last follow-up (mean follow-up duration, 27 months). LIMITATIONS: This was a
      retrospective study with a relatively small number of patients. CONCLUSION: Solid
      organ malignancy should be considered as a possible cause of CSVV of unknown
      origin. In contrast to previous reports, our patients were more likely to respond
      to immunosuppressive therapies without treatment of the associated malignancy and
      to be alive at last follow-up.

PMID- 21093107
TI  - The role of informed consent in risks recall in otorhinolaryngology surgeries:
      verbal (nonintervention) vs written (intervention) summaries of risks.
AB  - BACKGROUND: Informed consent is a phrase often used in the law to indicate that
      the consent a person gives meets certain minimum standards. It relies on
      patients' ability to understand risk information. Evidence suggests that people
      may extract the gist of any risk information to make medical decisions. Existing
      evidence also suggests that there is an inverse relationship between the
      perception of risk and the perception of benefit. Informed consent is the method
      by which fully informed, rational persons may be involved in choices about their
      health care. AIM: The aims of this study were to study how much patients remember
      of the risks discussed with them about their otolaryngologic surgery and to
      evaluate whether a simple intervention, the addition of an information handout,
      improves their recall. METHODS: This was a prospective study carried out between
      January and December 2009 in the Department of Otorhinolaryngology, University of
      Ilorin teaching hospital. Fifty patients undergoing a variety of
      otorhinolaryngologic procedures, including mastoidectomy, tympanoplasty, nasal
      polypectomy, rhinotomy, maxillectomy, and laryngoscopy, were verbally consented
      by the operating surgeon with a standard checklist of potential surgical
      complications and adverse effects. Three surgeons participated in the study.
      Patients were stratified into 2 groups: a higher education group and a lower
      education group. Within each group, patients were randomized to either a control
      group, consisting of a verbal explanation only, or an intervention group, which
      added a written handout to the verbal explanation. A follow-up telephone
      interview was conducted at an average of 20.6 days (range, 14-53 days) to survey
      for recall of the complications discussed. The main outcome measure is risk
      recall. This was analyzed by education level and written sheet intervention.
      Other parameters examined were patient demographics and time elapsed from when
      the consent was obtained. RESULTS: Of the 50 patients involved in the study, 30
      were men and 20 were women, with male/female ratio of 1.5:1.0. The average age
      was 43 years (range, 16-76 years). With respect to educational status, 26
      patients had the equivalent of high school or less (group 1), and 24 had some
      degree of postsecondary training (group 2). Overall recall of potential
      complications was 56%. Those who received the handout recalled 67% of the
      complications overall, whereas those who did not receive the handout remembered
      51% of the complications. The difference was significant recall of the specific
      risks varied considerably. For those with potential risk of facial nerve
      paralysis, 88% of them recalled, which was the highest in the study. This was
      followed by hearing loss (85%) and nasal adhesion (23%). The least were
      anesthetic reactions (4%) and hoarseness (2%). Those who received the handout
      recalled 62% of the complications overall, whereas those who did not receive the
      handout remembered 51% the complications. CONCLUSION: The addition of a handout
      significantly alters recall of potential complications of otorhinolaryngologic
      surgery with the recall of specific risk highest for facial nerve paralysis.

PMID- 21093108
TI  - Head and neck osteosarcoma.
AB  - OBJECTIVE: The objective of the study was to discuss the optimal management and
      treatment outcomes for patients with head and neck osteosarcomas. STUDY DESIGN:
      Review article. METHODS: Review of the pertinent literature. RESULTS:
      Osteosarcomas account for approximately 1% or less of all head and neck cancers.
      The vast majority occur in the mandible and maxilla. The median age is in the
      fourth decade, with a wide range. They are more likely to recur locally after
      treatment and distant metastases are observed less often than with the more
      common osteosarcomas arising in the long bones. The optimal treatment is complete
      resection. The role of adjuvant chemotherapy is ill-defined. The vast majority of
      recurrences are observed within 5 years. The 5-year disease-specific and overall
      survival rates are approximately 60% to 70%. CONCLUSIONS: Osteosarcoma of the
      head and neck is a rare entity that occurs primarily in the mandible and maxilla.
      The optimal treatment is surgery. Adjuvant radiotherapy should be considered for
      those with close or positive margins. The role of adjuvant chemotherapy is ill
      defined. The likelihood of cure is approximately 60% to 70%.

PMID- 21093109
TI  - Age affects chunk-based, but not rule-based learning in artificial grammar
      acquisition.
AB  - Explicit learning is well known to decline with age, but divergent results have
      been reported for implicit learning. Here, we assessed the effect of aging on
      implicit vs. explicit learning within the same task. Fifty-five young (mean 32
      years) and 55 elderly (mean 64 years) individuals were exposed to letter strings
      generated by an artificial grammar. Subsequently, participants classified novel
      strings as grammatical or nongrammatical. Acquisition of superficial ("chunk
      based") and structural ("rule-based") features of the grammar were analyzed
      separately. We found that overall classification accuracy was diminished in the
      elderly, driven by decreased performance on items that required chunk-based
      knowledge. Performance on items requiring rule-based knowledge was comparable
      between groups. Results indicate that rule-based and chunk-based learning are
      differentially affected by age: while rule-based learning, reflecting implicit
      learning, is preserved, chunk-based learning, which contains at least some
      explicit learning aspects, declines with age. Our findings may explain divergent
      results on implicit learning tasks in previous studies on aging. They may also
      help to better understand compensatory mechanisms during the aging process.

PMID- 21093110
TI  - No association of psychosis in Alzheimer disease with neurodegenerative pathway
      genes.
AB  - Psychotic symptoms occur in approximately 40% of subjects with Alzheimer disease
      (AD with psychosis; AD + P) and identify a subgroup with more rapid cognitive
      decline. We evaluated in 867 AD subjects the association of AD + P with genes
      which may modify the pathological process via effects on the accumulation of
      amyloid beta (Abeta) protein and/or hyperphosphorylated microtubule-associated
      protein tau (MAPT): amyloid precursor protein (APP), beta-site amyloid precursor
      protein cleaving enzyme (BACE1), sortilin-related receptor (SORL1), and MAPT.
      Each gene was thoroughly interrogated with tag single-nucleotide polymorphisms
      (SNPs), and gene-based tests were used to enhance power. We found no association
      of these genes with AD + P.

PMID- 21093111
TI  - Synthesis and antifungal activity of some substituted phenothiazines and related
      compounds.
AB  - Several phenothiazines and related compounds were synthesized and their
      antifungal activity was evaluated in vitro. The results observed for alpha-chloro
      N-acetyl phenothiazine led us to choose this compound as a lead in the search of
      antifungal agents.

PMID- 21093112
TI  - Chiral 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimine analogues as
      novel potent neonicotinoids: Synthesis, insecticidal evaluation and molecular
      docking studies.
AB  - A new series of 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimines (4a-4x)
      were designed and synthesized as novel chiral neonicotinoid analogues. The single
      crystal structure of 4n was further determined by X-ray diffraction, and its S
      configuration was confirmed. Preliminary bioassay showed that compound 4e, 4k,
      4u, 4v exhibited excellent insecticidal activities at 100 mg/L, while 4k had >90%
      mortality at 10 mg/L, which suggested it could be used as a lead for future
      development. Modeling the inhibitor-nAChR complexes by molecular docking studies
      explained the structure-activity relationships observed in vitro, and revealed an
      intriguing molecular binding mode at the active site of nAChR, which raised the
      possibility that these analogues may arbitrate their insecticidal activity
      through a mechanism other than imidacloprid.

PMID- 21093113
TI  - Molecular modeling studies on imidazo[4,5-b]pyridine derivatives as Aurora A
      kinase inhibitors using 3D-QSAR and docking approaches.
AB  - 3D-QSAR and docking studies were performed on sixty imidazo[4,5-b]pyridine
      derivatives as Aurora A kinase inhibitors. The CoMFA and CoMSIA models using
      forthy-eight molecules in the training set, gave r(cv)(2) values of 0.774 and
      0.800, r(2) values of 0.975 and 0.977, respectively. The external validation
      indicated that both CoMFA and CoMSIA models possessed high predictive powers with
      r(pred)(2) values of 0.933 and 0.959, r(m)(2) values of 0.883 and 0.915,
      respectively. 3D contour maps generated from the two models along with docking
      binding structures have identified several key structural requirements
      responsible for the activity. A set of thirty new analogues were proposed by
      utilizing the results revealed in the present study, and were predicted with
      significantly improved potencies in the developed models.

PMID- 21093114
TI  - Self-organizing molecular field analysis on human beta-secretase nonpeptide
      inhibitors: 5, 5-disubstituted aminohydantoins.
AB  - 5, 5-disubstituted aminohydantoins have been recently reported as potent and
      selective human beta-secretase (BACE-1) inhibitors. Self-Organizing Molecular
      Field Analysis (SOMFA) is used to study the correlation between the molecular
      properties and biological activities of the 5, 5-disubstituted aminohydantoins
      inhibitors. Four different alignments and two charge-assigning methods were
      investigated. The model derived from the superposition of docked conformation
      with AM1 charge showed satisfied predictive ability, which has good non-cross
      validated r(2) (0.842), cross-validated q(2) (0.792), F-test value (254.75) and
      satisfied predictive ability r(2)(pred) (0.721). Analysis of SOMFA model may
      provide some useful information in the design of BACE-1 inhibitors with better
      spectrum of activity.

PMID- 21093115
TI  - Antifungal agents. Part 4: Synthesis and antifungal activities of novel
      indole[1,2-c]-1,2,4-benzotriazine derivatives against phytopathogenic fungi in
      vitro.
AB  - A series of novel indole[1,2-c]-1,2,4-benzotriazine derivatives were obtained by
      a modified Sandmeyer reaction in the presence of tert-butylnitrite (t-BuONO). As
      compared with hymexazol, a commercially available agricultural fungicide, at the
      concentration of 50 MUg/mL, two indole[1,2-c]-1,2,4-benzotriazines, 5h and 5k,
      exhibited the more promising and pronounced antifungal activities in vitro
      against five phytopathogenic fungi. It clearly demonstrated that introduction of
      appropriate substituents on the indolyl ring of indole[1,2-c]-1,2,4-benzotriazine
      (5a) would lead to the more potent derivatives.

PMID- 21093116
TI  - Anti-breast cancer activity of some novel 1,2-dihydropyridine, thiophene and
      thiazole derivatives.
AB  - A variety of novel 1,2-dihydropyridines 10-17, thiophenes 18-21 and thiazole 22
      having a biologically active sulfone moiety were obtained via the reaction of 2
      cyano-N'-[1-(4-(piperidin-1-ylsulfonyl) phenyl) ethylidene] acetohydrazide 3 with
      a variety of reagents. The structures of the newly synthesized compounds were
      confirmed by elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data.
      All the newly synthesized compounds were evaluated for their in-vitro anticancer
      activity against human breast cancer cell line (MCF7). Compounds 15 and 11 with
      IC(50) values (20.6, 25.5 MUM) exhibited better activity than Doxorubicin as a
      reference drug with IC(50) value (32.02 MUM), while compound 14 is nearly as
      active as Doxorubicin as positive control.

PMID- 21093117
TI  - Novel isatinyl thiosemicarbazones derivatives as potential molecule to combat HIV
      TB co-infection.
AB  - A series of novel 5-substituted-1-(arylmethyl/alkylmethyl)-1H-indole-2,3-dione-3
      (N-hydroxy/methoxy thiosemicarbazone) analogues were synthesized and evaluated
      for their anti-HIV activity and anti-tubercular activity in both log phase and
      starved cultures. The compound 2-(1-{[4-(4-chlorophenyl)tetrahydropyrazin-1(2H)
      yl]methyl}-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-yliden)-N-(methyloxy)hydrazine-1
      carbothioamide (B21) displayed promising activity against the replication of HIV
      1 cells (EC(50) 1.69 MUM). In anti-mycobacterial screening B21 proved effective
      in inhibiting the growth of both log phase (MIC 3.30 MUM) and starved (MIC 12.11
      MUM) MTB cultures. Isocitrate lyase enzyme having momentous implication in
      persistent TB was shown to be inhibited by 1-cyclopropyl-6-fluoro-7-[4-{[5-methyl
      3-((Z)-2-{[(methyloxy)amino]carbothioyl}hydrazono)-2-oxo-1H-indol-1(2H)
      yl]methyl}tetrahydropyrazin-1(2H)-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic
      acid (B30) with 63.44% inhibition at 10 mM.

PMID- 21093118
TI  - Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. part
      3.
AB  - A number of 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine with 3-(1,2,3,6
      tetrahydro-pyridin-4-yl)-1H-indole or 2-methyl-3-(1,2,3,6-tetrahydro-pyridin-4
      yl)-1H-indole residues were synthesized for further investigation of SAR in a
      group of pyrido[1,2-c]pyrimidine derivatives with dual 5-HT(1A)/SERT activity.
      Compounds 8a-8p were found to be potent ligands for both 5-HT(1A) and SERT with
      K(i) ranging from 28,3 to 642 nM and 42,4 nM-1,8 MUM, respectively. Moreover
      compounds 8a, 8b, 8c, 8d, 8e and 8g were found to be selective agonists, while 8i
      as an antagonist of 5-HT(1A) presynaptic receptors in the inducible hypothermia
      test in mice.

PMID- 21093119
TI  - Penetratin analogues acting as antifungal agents.
AB  - The synthesis, in vitro evaluation, and conformational study of penetratin
      analogues acting as antifungal agents are reported. Different peptides
      structurally related with penetratin were evaluated. Analogues of penetratin rich
      in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK
      NH(2), a synthetic 20 amino acid peptide was also evaluated. These penetratin
      analogues displayed antifungal activity against human pathogenic strains
      including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide,
      a well-known cell penetrating peptide, did not show a significant antifungal
      activity against fungus tested here. We also performed a conformational study by
      means experimental and theoretical approaches (CD spectroscopic measurements and
      MD simulations). The electronic structure analysis was carried out from Molecular
      Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio
      calculations. Our experimental and theoretical results permitted us to identify a
      topographical template which may provide a guide for the design of new peptides
      with antifungal effects.

PMID- 21093120
TI  - [Inflammatory bowel disease and lower limb lymphedema: a fortuitous
      association?].
AB  - INTRODUCTION: Extra-intestinal manifestations of chronic inflammatory bowel
      disease (CIBD) are various. Cases of genital lymphedema has previously been
      reported in Crohn's disease. CASE REPORTS: We report two women aged 57 and 68
      years who presented with a lower limb lymphedema 8 and 20 years after a diagnosis
      of CIBD (Crohn's disease and ulcerative colitis), respectively. At the time of
      diagnosis of lymphedema, CIBD was asymptomatic. CONCLUSION: Pathophysiological
      mechanisms of this rare manifestation are unclear and lymphedema outcome is
      unrelated to CIBD activity.

PMID- 21093121
TI  - The first undergraduate nursing students: a quantitative historical study of the
      Edinburgh degrees, 1960-1985.
AB  - AIMS: The aim of this article is to examine the experiences of the first 25 years
      of undergraduate nurses at the University of Edinburgh using a quantitative
      historical methodology. BACKGROUND: In 1960, the University of Edinburgh, Nursing
      Studies Unit commenced the first undergraduate degree with nursing in the United
      Kingdom. By 1967, nursing was a component of the academic award itself. METHODS:
      A questionnaire was sent to 225 graduates of nursing at the University of
      Edinburgh through the alumni office. The questionnaire combined biographical data
      and a Likert scale. DATA/RESULTS: Quantitative data can provide the historian
      with wide-ranging information about large groups of people, in this case
      undergraduate nurses. Although some of the responses may be more positive than
      what the participants felt at the time, the material provides useful information
      as to the experiences of early undergraduate nurses. CONCLUSION: This article has
      generated a previously unknown material related to the experiences of the early
      undergraduate nurses at Edinburgh. For example, the respondents did not feel that
      the course was too difficult and it appears that the University was accepting
      nursing as an academic subject. The additional qualitative data provided by the
      respondents has offered potential for further study.

PMID- 21093122
TI  - Learning preference as a predictor of academic performance in first year
      accelerated graduate entry nursing students: a prospective follow-up study.
AB  - The growth of accelerated graduate entry nursing programs has challenged
      traditional approaches to teaching and learning. To date, limited research has
      been undertaken in the role of learning preferences, language proficiency and
      academic performance in accelerated programs. Sixty-two first year accelerated
      graduate entry nursing students, in a single cohort at a university in the
      western region of Sydney, Australia, were surveyed to assess their learning
      preference using the Visual, Aural, Read/write and Kinaesthetic (VARK) learning
      preference questionnaire, together with sociodemographic data, English language
      acculturation and perceived academic control. Six months following course
      commencement, the participant's grade point average (GPA) was studied as a
      measurement of academic performance. A 93% response rate was achieved. The
      majority of students (62%) reported preference for multiple approaches to
      learning with the kinaesthetic sensory mode a significant (p=0.009) predictor of
      academic performance. Students who spoke only English at home had higher mean
      scores across two of the four categories of VARK sensory modalities, visual and
      kinaesthetic compared to those who spoke non-English. Further research is
      warranted to investigate the reasons why the kinaesthetic sensory mode is a
      predictor of academic performance and to what extent the VARK mean scores of the
      four learning preference(s) change with improved English language proficiency.

PMID- 21093123
TI  - Genetics and genomics in nursing: evaluating Essentials implementation.
AB  - The goal of the present study was to determine how well selected essential
      knowledge elements and practice indicators from the Essential Nursing
      Competencies and Curricula Guidelines in Genetics and Genomics (Essentials) were
      being achieved. A cross-sectional survey design was used. Eligible participants
      were recruited from a convenience sample of attendees at a national nursing
      conference in October 2008. Of the 200 surveys distributed, 47 usable surveys
      (24%) were returned. The majority of respondents were current nursing faculty
      (45.7%). Only 36% of all respondents had read the Essentials document. Less than
      30% of respondents had attended any recent genetic/genomic content continuing
      education. There were significant associations between having read the Essentials
      document and obtaining both recent genomic continuing education and conducting
      genetic research (p<0.01). The results from this survey indicate that the
      Essentials have not been well disseminated outside of those primarily interested
      in the subject matter. They further indicate that respondents were not well
      prepared to respond to patient queries about genetic testing. Nurse educators
      must be adequately educated to address genomics as it will eventually become
      commonplace, with global applications in health promotion, disease prevention,
      and diagnostic and treatment strategies.

PMID- 21093124
TI  - Reframing the Australian nurse teacher competencies: do they reflect the 'REAL'
      world of nurse teacher practice?
AB  - The Australian nurse teacher competencies were introduced in 1996; however, the
      researchers perceived that changes to the health care system and a nursing
      workforce shortage may have affected nurse teacher roles over the past decade.
      This study aimed to explore perceptions of nurse teachers on the applicability of
      the current Australian nurse teacher competencies to practice, and modify the
      nurse teacher competencies to better reflect current practice. Methodology
      utilized mixed methods, and data collection was via focus groups, telephone
      interviews, and survey data. Results revealed that participants were mostly
      positive about the original competency statements, although there were some
      variations between items. Themes that emerged from the qualitative data were:
      changing trends in health care; preparation for teaching; understanding of the
      competencies, contextual influences on education role; nurse teachers as change
      agents, and resource management. Conclusions were that the Australian nurse
      teacher competencies (1996) were reflective of the current generic roles of nurse
      teachers however some of the competencies needed reframing to meet the current
      needs of nurse teachers. However, changes needed to be made in areas such as
      reducing complex language, inclusion of technology, and cultural competencies.
      Nurse teachers were supportive of the research because they valued the teacher
      competencies for reflection on their practice and the development of portfolios,
      job descriptions and performance appraisals.

PMID- 21093125
TI  - The transferability of information and communication technology skills from
      university to the workplace: a qualitative descriptive study.
AB  - AIM: This paper presents the findings from a study that explored whether the
      information and communication technology (ICT) skills nurses acquired at
      university are relevant and transferable to contemporary practice environments.
      BACKGROUND: Whilst universities have attempted to integrate information and
      communication technology into nursing curricula it is not known whether the
      skills developed for educational purposes are relevant or transferable to
      clinical contexts. METHODS: A qualitative descriptive study was used to explore
      the perspectives of a small group of new graduate nurses working in a
      regional/semi-metropolitan healthcare facility in New South Wales, Australia.
      Semi-structured interviews were used and the data thematically analysed.
      FINDINGS: The themes that emerged from the study are presented in accordance with
      the conceptual framework and structured under the three headings of pre-transfer,
      transition and post-transfer. The transferability of information and
      communication technology skills from university to the workplace is impacted by a
      range of educational, individual, organisational and contextual factors.
      CONCLUSION: Access to adequate ICT and the necessary training opportunities
      influences new graduates' work satisfaction and their future employment
      decisions. The ability to effectively use information and communication
      technology was viewed as essential to the provision of quality patient care.

PMID- 21093126
TI  - Po-210 and Pb-210 as atmospheric tracers and global atmospheric Pb-210 fallout: a
      review.
AB  - Over the past ~ 5 decades, the distribution of (222)Rn and its progenies (mainly
      (210)Pb, (210)Bi and (210)Po) have provided a wealth of information as tracers to
      quantify several atmospheric processes that include: i) source tracking and
      transport time scales of air masses; ii) the stability and vertical movement of
      air masses iii) removal rate constants and residence times of aerosols; iv)
      chemical behavior of analog species; and v) washout ratios and deposition
      velocities of aerosols. Most of these applications require that the sources and
      sink terms of these nuclides are well characterized. Utility of (210)Pb, (210)Bi
      and (210)Po as atmospheric tracers requires that data on the (222)Rn emanation
      rates is well documented. Due to low concentrations of (226)Ra in surface waters,
      the (222)Rn emanation rates from the continent is about two orders of magnitude
      higher than that of the ocean. This has led to distinctly higher (210)Pb
      concentrations in continental air masses compared to oceanic air masses. The
      highly varying concentrations of (210)Pb in air as well the depositional fluxes
      have yielded insight on the sources and transit times of aerosols. In an ideal
      enclosed air mass (closed system with respect to these nuclides), the residence
      times of aerosols obtained from the activity ratios of (210)Pb/(222)Rn,
      (210)Bi/(210)Pb, and (210)Po/(210)Pb are expected to agree with each other, but a
      large number of studies have indicated discordance between the residence times
      obtained from these three pairs. Recent results from the distribution of these
      nuclides in size-fractionated aerosols appear to yield consistent residence time
      in smaller-size aerosols, possibly suggesting that larger size aerosols are
      derived from resuspended dust. The residence times calculated from the
      (210)Pb/(222)Rn, (210)Bi/(210)Pb, and (210)Po/(210)Pb activity ratios published
      from 1970's are compared to those data obtained in size-fractionated aerosols in
      this decade and possible reasons for the discordance is discussed with some key
      recommendations for future studies. The existing global atmospheric inventory
      data of (210)Pb is re-evaluated and a 'global curve' for the depositional fluxes
      of (210)Pb is established. A current global budget for atmospheric (210)Po and
      (210)Pb is also established. The relative importance of dry fallout of (210)Po
      and (210)Pb at different latitudes is evaluated. The global values for the
      deposition velocities of aerosols using (210)Po and (210)Pb are synthesized.

PMID- 21093127
TI  - Temporal signatures of advective versus diffusive radon transport at a geothermal
      zone in Central Nepal.
AB  - Temporal variation of radon-222 concentration was studied at the Syabru-Bensi hot
      springs, located on the Main Central Thrust zone in Central Nepal. This site is
      characterized by several carbon dioxide discharges having maximum fluxes larger
      than 10 kg m(-2) d(-1). Radon concentration was monitored with autonomous
      BarasolTM probes between January 2008 and November 2009 in two small natural
      cavities with high CO(2) concentration and at six locations in the soil: four
      points having a high flux, and two background reference points. At the reference
      points, dominated by radon diffusion, radon concentration was stable from January
      to May, with mean values of 22 +/- 6.9 and 37 +/- 5.5 kBq m(-3), but was affected
      by a large increase, of about a factor of 2 and 1.6, respectively, during the
      monsoon season from June to September. At the points dominated by CO(2)
      advection, by contrast, radon concentration showed higher mean values 39.0 +/-
      2.6 to 78 +/- 1.4 kBq m(-3), remarkably stable throughout the year with small
      long-term variation, including a possible modulation of period around 6 months. A
      significant difference between the diffusion dominated reference points and the
      advection-dominated points also emerged when studying the diurnal S(1) and semi
      diurnal S(2) periodic components. At the advection-dominated points, radon
      concentration did not exhibit S(1) or S(2) components. At the reference points,
      however, the S(2) component, associated with barometric tide, could be identified
      during the dry season, but only when the probe was installed at shallow depth.
      The S(1) component, associated with thermal and possibly barometric diurnal
      forcing, was systematically observed, especially during monsoon season. The
      remarkable short-term and long-term temporal stability of the radon concentration
      at the advection-dominated points, which suggests a strong pressure source at
      depth, may be an important asset to detect possible temporal variations
      associated with the seismic cycle.

PMID- 21093128
TI  - Modelling the behaviour of 210Po in high temperature processes.
AB  - In several Naturally Occurring Radioactive Material (NORM) industries, relatively
      high temperatures are used as part of their industrial processes. In coal
      combustion, as occur in other high temperature processes, an increase of the
      activity concentration of every natural radioisotope is produced both, in
      residues and by-products. An additional increase can be observed in the activity
      concentration of radionuclides of elements with low boiling point. This work is
      centred in the increase of polonium, more precisely in its radioisotope Po-210,
      present in the natural chains, and with a half-life long enough to be considered
      for radiation protection purposes. This additional increase appears mainly in the
      residual particles that are suspended in the flue gases: the fly-ashes. Besides,
      scales, with a high concentration of this radioisotope, were observed. These
      scales are produced on surfaces with a temperature lower than the boiling point
      of the chemical element. Both, the accumulation in particles and the production
      of scales are attributed to condensation effects. When effective doses for the
      public and the workers are evaluated, taking into account these increases in
      activity concentrations, the use of theoretical models is necessary. In this work
      a theoretical description of those effects is presented. Moreover, a verification
      of the predictions of the model was performed by comparing them with measurements
      carried on in coal-fired power plants. The same description here presented is
      applicable in general to the behaviour of Po-210 in other NORM industries where
      high temperature processes involving raw materials are used, as can be ceramic,
      cement production, tiles production or steel processing.

PMID- 21093129
TI  - The extra-tonsillar approach to the styloid process.

PMID- 21093130
TI  - Effect of forearm axially rotated posture on shoulder load and shoulder abduction
      / flexion angles in one-armed arrest of forward falls.
AB  - BACKGROUND: Falling onto the outstretched hand is the most common cause of upper
      extremity injury. This study develops an experimental model for evaluating the
      shoulder load during a simulated forward fall onto one hand with three different
      forearm axially rotated postures, and examines the shoulder abduction angle and
      shoulder flexion angle in each case. METHODS: Fifteen healthy young male subjects
      with an average age of 23.7 years performed a series of one-armed arrests from a
      height of 5 cm onto a force plate. The kinematics and kinetics of the upper
      extremity were analyzed for three different forearm postures, namely 45 degrees 
      externally rotated, non-rotated, and 45 degrees  internally rotated. FINDINGS:
      The shoulder joint load and shoulder abduction/flexion angles were significantly
      dependent on the rotational posture of the forearm. The shoulder medio-lateral
      shear forces in the externally rotated group were found to be 1.61 and 2.94 times
      higher than those in the non-rotated and internally rotated groups, respectively.
      The shoulder flexion angles in the externally rotated, non-rotated and internally
      rotated groups were 0.6 degrees , 8.0 degrees  and 19.2 degrees , respectively,
      while the corresponding shoulder abduction angles were 6.1 degrees , 34.1 degrees
      and 46.3 degrees , respectively. INTERPRETATION: In falls onto the outstretched
      hand, an externally rotated forearm posture should be avoided in order to reduce
      the medio-lateral shear force acting on the shoulder joint. In falls of this
      type, a 45 degrees  internally rotated forearm posture represents the most
      effective fall strategy in terms of minimizing the risk of upper extremity
      injuries.

PMID- 21093131
TI  - The effects of prosthetic ankle dorsiflexion and energy return on below-knee
      amputee leg loading.
AB  - BACKGROUND: Prosthetic devices are intended to return lower limb amputees to
      their pre-amputation functional status. However, prosthetic devices designed for
      unilateral below-knee amputees have yet to completely restore the biomechanical
      functions normally provided by the ankle muscles, leading to gait asymmetries and
      increased reliance on their intact leg. In an effort to improve amputee gait,
      energy storage and return feet have been developed that store mechanical energy
      in elastic structures in early to mid-stance and return it in late stance.
      However, little is known regarding how ankle compliance and the level of energy
      return influences walking mechanics. The purpose of this study was to identify
      the influence of prosthetic ankle dorsiflexion and energy storage and return on
      leg loading during steady-state walking. METHODS: Compliant ankles with different
      stiffness levels were attached to a Seattle Lightfoot2 in different orientations
      (forward- and reverse-facing). FINDINGS: The ankles decreased residual leg
      vertical ground reaction forces in late stance, increased residual leg propulsive
      ground reaction force impulses and increased residual leg knee joint extensor
      moments. The reverse-facing ankles increased residual leg vertical ground
      reaction forces in early stance, and the compliant forward-facing ankle increased
      residual leg braking impulses. In contrast to previous studies, increased energy
      storage and return from compliant ankles did not decrease hip joint powers or the
      intact leg vertical ground reaction forces. INTERPRETATION: These results provide
      insight into the relationships between ankle dorsiflexion, energy storage and
      return, and leg loading, which may lead to more effective prosthetic devices to
      improve amputee gait.

PMID- 21093132
TI  - How the redox state of tobacco 'Bel-W3' is modified in response to ozone and
      other environmental factors in a sub-tropical area?
AB  - This study intended to determine whether the redox state in plants of Nicotiana
      tabacum 'Bel-W3' fluctuates in response to the environmental factors in a sub
      tropical area contaminated by ozone (Sao Paulo, SE-Brazil) and which
      environmental factors are related to this fluctuation, discussing their
      biomonitoring efficiency. We comparatively evaluated the indicators of redox
      state (ascorbic acid, glutathione, superoxide dismutase, ascorbate peroxidase,
      and glutathione reductase) and leaf injury in 17 field experiments performed in
      2008. The redox state was explained by the combined effects of chronic levels of
      O(3) and meteorological variables 4-6 days prior to the plant sampling. Moderate
      leaf injury was observed in most cases. The redox state of tobacco decreases few
      days after their placement in the sub-tropical environment, causing them to
      become susceptible to oxidative stress imposed by chronic doses of O(3). Its
      bioindicator efficiency would not be diminished in such levels of atmospheric
      contamination.

PMID- 21093133
TI  - The role of root hairs in cadmium acquisition by barley.
AB  - The role of root hairs in Cd acquisition from soil was investigated in three pot
      experiments using a root hairless mutant (bald root barley, brb) and its wild
      type (WT) cultivar of barley (Hordeum vulgare). brb had significantly lower
      concentrations and lower total amounts of Cd in shoots than WT. The Cd uptake
      efficiency based on total root length was 8-45% lower in brb than in WT. The
      difference between brb and WT increased with increasing extractable Cd in soil
      under the experimental conditions used. Additions of phosphate to soil decreased
      Cd extractability. Both soil and foliar additions of phosphate decreased root
      length, and root hair formation in WT. These effects resulted in decreased Cd
      uptake with increasing P supply. Cd uptake in WT correlated significantly with
      root length, root hair length and density, and soil extractable Cd. Root hairs
      contribute significantly to Cd uptake by barley.

PMID- 21093134
TI  - Use of reporter-gene based bacteria to quantify phenanthrene biodegradation and
      toxicity in soil.
AB  - A phenanthrene-degrading bacterium, Sphingomonas paucimobilis EPA505 was used to
      construct two fluorescence-based reporter strains. Strain D harboring gfp gene
      was constructed to generate green fluorescence when the strain started to
      biodegrade phenanthrene. Strain S possessing gef gene was designed to die once
      phenanthrene biodegradation was initiated and thus to lose green fluorescence
      when visualized by a live/dead cell staining. Confocal laser scanning microscopic
      observation followed by image analysis demonstrates that the fluorescence
      intensity generated by strain D increased and the intensity by strain S decreased
      linearly at the phenanthrene concentration of up to 200 mg/L. Such quantitative
      increase and decrease of fluorescence intensity in strain D (i.e., from 1 to
      11.90 +/- 0.72) and strain S (from 1 to 0.40 +/- 0.07) were also evident in the
      presence of Ottawa sand spiked with the phenanthrene up to 1000 mg/kg. The
      potential use of the reporter strains in quantitatively determining biodegradable
      or toxic phenanthrene was discussed.

PMID- 21093135
TI  - Modeling time-dependent toxicity to aquatic organisms from pulsed exposure of
      PAHs in urban road runoff.
AB  - Understanding of the magnitude of urban runoff toxicity to aquatic organisms is
      important for effective management of runoff quality. In this paper, the aquatic
      toxicity of polycyclic aromatic hydrocarbons (PAHs) in urban road runoff was
      evaluated through a damage assessment model. Mortality probability of the
      organisms representative in aquatic environment was calculated using the
      monitored PAHs concentration in road runoff. The result showed that the toxicity
      of runoff in spring was higher than those in summer. Analysis of the time
      dependent toxicity of series of runoff water samples illustrated that the
      toxicity of runoff water in the final phase of a runoff event may be as high as
      those in the initial phase. Therefore, the storm runoff treatment systems or
      strategies designed for capture and treatment of the initial portion of runoff
      may be inappropriate for control of runoff toxicity.

PMID- 21093136
TI  - Uranium bioaccumulation and biological disorders induced in zebrafish (Danio
      rerio) after a depleted uranium waterborne exposure.
AB  - Because of its toxicity and its ubiquity within aquatic compartments, uranium (U)
      represents a significant hazard to aquatic species such as fish. In a previous
      study, we investigated some biological responses in zebrafish either exposed to
      depleted or to enriched U (i.e., to different radiological activities). However,
      results required further experiments to better understand biological responses.
      Moreover, we failed to clearly demonstrate a significant relationship between
      biological effects and U radiological activity. We therefore chose to herein
      examine U bioaccumulation and induced effects in zebrafish according to a
      chemical dose-response approach. Results showed that U is highly bioconcentrated
      in fish, according to a time- and concentration-dependent model. Additionally,
      hepatic antioxidant defenses, red blood cells DNA integrity and brain
      acetylcholinesterase activity were found to be significantly altered. Generally,
      the higher the U concentration, the sooner and/or the greater the effect,
      suggesting a close relationship between accumulation and effect.

PMID- 21093137
TI  - Do area characteristics predict change in moderate-to-vigorous physical activity
      from ages 11 to 15 years?
AB  - In light of geographical and epidemiological research suggesting that the
      socioeconomic environment beyond the family may influence children's physical
      activity, this study investigated the extent to which neighbourhood socioeconomic
      conditions predict change in physical activity from ages 10 through 15 years,
      controlling for the attributes of the individual child and family. Data came from
      889 children participating in the National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development cohort study.
      Accelerometers measured Moderate-to-Vigorous Physical Activity (MVPA) during the
      week and weekend, when the children were aged 10, 11, and 15 years. Selected US
      census block variables were used to create 'independent' area measures of
      economic deprivation and social fragmentation scores for child's area of
      residence at age 10 years. Also, parents' perception of neighbourhood social
      cohesion was measured in terms of relationships with neighbours. All analyses
      controlled for participant characteristics: gender, ethnicity, household income
      to-needs ratio, maternal education, and for United States region of residence.
      Growth curve analyses indicated that whereas social fragmentation did not predict
      MVPA over time, greater area deprivation at age 10 years was associated with
      lower weekday MVPA for boys at 10 years (beta=-0.5, p=0.03) and these differences
      persisted to age 11 and 15 years. This relationship was reversed for girls.
      Weekend MVPA was not significantly associated with the level of deprivation in
      the place of residence at age 10 years. Although the census measure of social
      fragmentation in the area of residence showed no significant association with
      MVPA, parent-reported neighbourhood social cohesion was positively associated
      with weekday (beta=2.0, p<0.01) and weekend (beta=3.1, p<0.01) MVPA minutes
      across time. This association was most pronounced for boys. Area level factors
      may be determinants of physical activity among children and youth in complex ways
      and parental perception of area social environment may be as important for
      children's activity levels as 'independently assessed' socioeconomic conditions.

PMID- 21093138
TI  - [Factor associated with prolonged hospital stay in patients with H1N1 virus
      influenza].

PMID- 21093139
TI  - [Mounier-Kuhn syndrome diagnosed in an adult].

PMID- 21093140
TI  - Disposable laryngeal tube suction: standard insertion technique versus two
      modified insertion techniques for patients with a simulated difficult airway.
AB  - OBJECTIVE: The disposable laryngeal tube suction (LTS-D) is a supraglottic airway
      device that can be used as an alternative to tracheal tube to provide
      ventilation. We tested the hypothesis that, with a frontal jaw thrust insertion
      technique (FIT/JT), the rate of correct placement attempts in patients with a
      simulated difficult airway by means of a rigid cervical immobilization collar
      could be significantly increased compared to the standard insertion technique
      (SIT) recommended by the manufacturer. METHODS: 70 adult patients undergoing
      trauma surgery under general anaesthesia had an LTS-D inserted, randomly assigned
      to the SIT or FIT/JT. In the FIT/JT, the operator was standing in front of the
      patient's head, and forced chin lift to create sufficient retropharyngeal space
      was performed. The rate of successful tube placements within 180s and with a
      maximum of two attempts was the main outcome variable. To distinguish between the
      effects of the frontal approach and the jaw thrust manoeuvre, a third group was
      studied after completion of the SIT and FIT/JT groups. The standard insertion
      technique, but with a jaw thrust manoeuvre (SIT/JT), was employed in another 35
      consecutive patients. RESULTS: Overall placement success was 49% (SIT, 17/35
      patients, P<0.001), 91% (SIT/JT, 32/35 patients) and 100% (FIT/JT). The time
      required for successful insertion was shortest in the FIT/JT group (23+/-6s), and
      significantly longer in the SIT/JT (42+/-29s, P<0.001) and SIT groups (51+/-29s,
      P<0.0001). CONCLUSION: In anaesthetised patients with a simulated difficult
      airway created with a rigid cervical collar, the overall LTS-D placement success
      was significantly higher when a jaw thrust manoeuvre was performed, regardless of
      the particular technique used to introduce the LTS-D. Therefore, an intense jaw
      thrust manoeuvre should be performed whenever an LTS-D is being inserted.

PMID- 21093141
TI  - Mechanical chest compressions with trapezoidal waveform improve haemodynamics
      during cardiac arrest.
AB  - BACKGROUND: During manual chest compressions for cardiac arrest the waveforms of
      chest compressions are generally sinusoidal, whereas mechanical chest compression
      devices can have different waveforms, including trapezoidal. We studied the
      haemodynamic differences of such waveforms in a porcine model of cardiac arrest.
      METHODS: Eight domestic pigs (weight 31+/-3kg) were anaesthetised and
      instrumented to continuously monitor aortic (AP) and right atrial pressure (RAP),
      carotid (CF) and cerebral cortical microcirculation blood flow (CCF). Coronary
      perfusion pressure (CPP) was calculated as the maximal difference between AP and
      RAP during diastole or decompression phase. After 4 min of electrically induced
      ventricular fibrillation, mechanical chest compressions were performed with four
      different waveforms in a factorial design, and in randomized sequence for 3 min
      each. Resulting differences are presented as mean with 95% confidence intervals.
      RESULTS: Mean AP and RAP were higher with trapezoid than sinusoid chest
      compressions, difference 5.7 (0.7, 11) and 6.3 (2.1, 11)mmHg, respectively. Flow
      measured as CF and CCF was also improved with trapezoidal waveform, difference 14
      (2.8, 26)ml/min and 11 (5.6, 17)% of baseline, respectively, with a parallel, non
      significant (P=0.08) trend for CPP. Active vs. passive decompression to zero
      level improved CF, but without even a trend for CPP. CONCLUSION: Trapezoid chest
      compressions and active decompression to zero level improved blood flow to the
      brain. The compression waveform is an additional factor to consider when
      comparing mechanical and manual chest compressions and when comparing different
      compression devices.

PMID- 21093142
TI  - Combined intrauterine and abdominal pregnancy following ICSI with delivery of two
      healthy viable fetuses: a case report.

PMID- 21093143
TI  - Comparative study of liponucleosides in Langmuir monolayers as cell membrane
      models.
AB  - Liponucleosides may assist the anchoring of nucleic acid nitrogen bases into
      biological membranes for tailored nanobiotechnological applications. To this end
      precise knowledge about the biophysical and chemical details at the membrane
      surface is required. In this paper, we used Langmuir monolayers as simplified
      cell membrane models and studied the insertion of five lipidated nucleosides.
      These molecules varied in the type of the covalently attached lipid group, the
      nucleobase, and the number of hydrophobic moieties attached to the nucleoside.
      All five lipidated nucleosides were found to be surface-active and capable of
      forming stable monolayers. They could also be incorporated into
      dipalmitoylphosphatidylcholine (DPPC) monolayers, four of which induced expansion
      in the surface pressure isotherm and a decrease in the surface compression
      modulus of DPPC. In contrast, one nucleoside possessing three alkyl chain
      modifications formed very condensed monolayers and induced film condensation and
      an increase in the compression modulus for the DPPC monolayer, thus reflecting
      the importance of the ability of the nucleoside molecules to be arranged in a
      closely packed manner. The implications of these results lie on the possibility
      of tuning nucleic acid pairing by modifying structural characteristics of the
      liponucleosides.

PMID- 21093144
TI  - Evaluating internalization of multifunctionality by farm diversification:
      evidence from educational dairy farms in Japan.
AB  - Farm diversification by farmers' open-door policy generates opportunities for
      farmers to internalize externalities of multifunctionality. Although the
      educational function of agriculture is an example of such an open-door policy and
      is attracting growing attention, this function has been little explored. To
      promote farm diversification in this direction, this paper examined how and to
      what degree farmers internalize externalities of multifunctionality by focusing
      on the educational function provided by dairy farming, i.e., farming experience
      services, in Japan. The main findings were as follows. First, we can say that the
      educational function is determined by ordinary technical jointness as well as
      institutional jointness, which is represented by food culture and the agrarian
      heritage. Both the technical and institutional jointness enhanced the
      externality. Because of these two working factors, there is a U-shaped
      relationship between farm diversification and provision of farming experience
      services. Second, however, an empirical evaluation indicated that farmers only
      partially internalize educational externalities by treating them as supplementary
      services combined with processed milk products. Therefore, appropriate integrated
      management of these newly emerging educational services to become a viable market
      should be fully addressed in the future, especially for family farms.

PMID- 21093145
TI  - Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate
      cancer in men with lower urinary tract symptoms and enlarged prostates in the
      Combination of Avodart and Tamsulosin trial.
AB  - BACKGROUND: A 23% relative risk reduction (RRR) in prostate cancer (PCa) was
      shown in men receiving dutasteride in the 4-yr Reduction by Dutasteride of
      Prostate Cancer Events study, in whom biopsies were protocol dependent.
      OBJECTIVE: Our aim was to explore PCa risk reduction in men with benign prostatic
      hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study,
      in which biopsies were undertaken for cause. DESIGN, SETTING, AND PARTICIPANTS:
      CombAT was a 4-yr randomized double-blind parallel group study in 4844 men >=50
      yr of age with clinically diagnosed moderate to severe BPH, International
      Prostate Symptom Score >=12, prostate volume >=30 ml, and serum prostate-specific
      antigen (PSA) 1.5-10 ng/ml. Men underwent annual PSA measurement and digital
      rectal examination (DRE), and prostate biopsies were performed for cause.
      INTERVENTION: All patients took tamsulosin 0.4 mg/d, dutasteride 0.5 mg/d, or a
      combination of both. MEASUREMENTS: The primary end point was incidence of PCa.
      Secondary end points included postbaseline prostate biopsy rates and Gleason
      score of cancers. RESULTS AND LIMITATIONS: Dutasteride (alone or in combination
      with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with
      tamsulosin monotherapy (95% confidence interval, 16-57%; p=0.002) and a 40%
      reduction in the likelihood of biopsy. There were similar reductions in low- and
      high-grade Gleason score cancers. The biopsy rate in the groups receiving
      dutasteride trended toward a higher diagnostic yield (combination: 29%,
      dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized
      approach to PCa diagnosis and grading. CONCLUSIONS: Dutasteride, alone or in
      combination with tamsulosin, significantly reduced the relative risk of PCa
      diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent
      with the increased usefulness of PSA for PCa detection, men receiving dutasteride
      had a numerically lower biopsy rate and higher yield of PCa on biopsy. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT00090103
      (http://www.clinicaltrials.gov/ct2/show/NCT00090103).

PMID- 21093146
TI  - Coleusin factor exerts cytotoxic activity by inducing G0/G1 cell cycle arrest and
      apoptosis in human gastric cancer BGC-823 cells.
AB  - Coleusin factor (CF), a kind of diterpenoids, is isolated and purified from the
      root of a Chinese tropical plant Coleus forskohlii by our laboratory. Our
      previous studies have demonstrated that CF significantly inhibits growth in some
      kinds of cancer cell lines. Here, we found that CF remarkably inhibited growth in
      human gastric cancer BGC-823 cells by decreasing cell proliferation, inducing
      G(0)/G(1) cell cycle arrest and apoptosis. CF also decreased the mitochondrial
      membrane potential in BGC-823 cells. Immunoblotting analysis revealed that CF
      significantly decreased the expressions of cyclinD1, Bcl-2, and Bcl-x(L),
      increased the expressions of cytosol cytochrome c, p53, p21, and Rb. In addition,
      CF significantly increased the expressions and activities of caspase-3 and -9.
      More importantly, CF potently inhibited the growth of BGC-823 cells xenografted
      in athymic nude mice with negligible body weight loss and damage towards the
      spleen. These results indicate that CF exerts a cytotoxic effect on BGC-823 cells
      by inducing cell cycle arrest and apoptosis.

PMID- 21093147
TI  - Mechanisms linking pathogens-associated inflammation and cancer.
AB  - It has been estimated that chronic infections with viruses, bacteria and
      parasites are the causative agents of 8-17% of global cancers burden.
      Carcinogenesis associated with infections is a complex process, often mediated by
      chronic inflammatory conditions and accumulating evidence indicate that a
      smouldering inflammation is a component of the tumor microenvironment and
      represents the 7th hallmark of cancer. Selected infectious agents promote a
      cascade of events culminating in chronic inflammatory responses, thus
      predisposing target tissues to increased cancer susceptibility. A causal link
      also exists between an inflammatory microenvironment, consisting of inflammatory
      cells and mediators, and tumor progression. Tumor-Associated Macrophages (TAM)
      represent the major inflammatory population present in tumors, orchestrating
      various aspects of cancer, including: diversion and skewing of adaptive
      responses; cell growth; angiogenesis; matrix deposition and remodelling;
      construction of a metastatic niche and actual metastasis; response to hormones
      and chemotherapeutic agents. Recent studies on human and murine tumors indicate
      that TAM show a remarkable degree of plasticity and functional heterogeneity,
      during tumour development. In established tumors, TAM acquire an M2 polarized
      phenotype are engaged in immunosuppression and the promotion of tumor
      angiogenesis and metastasis. Being a first line of the innate defence mechanisms,
      macrophages are also equipped with pathogen-recognition receptors, to sense the
      presence of danger signals, including onco-pathogens. Here we discuss the
      evidence suggesting a causal relationship between selected infectious agents and
      the pro-tumoral reprogramming of inflammatory cells, as well as its significance
      in tumor development. Finally, we discuss the implications of this phenomenon for
      both cancer prevention and therapy.

PMID- 21093148
TI  - PCA3: from basic molecular science to the clinical lab.
AB  - Prostate cancer is the second leading cause of cancer deaths in men in the United
      States. Use of the serum prostate specific antigen (PSA) test to screen men for
      prostate cancer since the late 1980s has improved the early detection of prostate
      cancer, however low specificity of the test translates to numerous false positive
      results and many unnecessary biopsies. New biomarkers to aid in prostate cancer
      diagnosis are emerging and prostate cancer gene 3 (PCA3) is one such marker. PCA3
      is a noncoding RNA that is highly over-expressed in prostate cancer tissue
      compared to benign tissue. A non-invasive test for PCA3 was developed using whole
      urine collected after a digital rectal exam (DRE). Numerous clinical studies have
      demonstrated the utility of PCA3 for the diagnosis of prostate cancer and some
      studies suggest that PCA3 may also have prognostic value. The use of PCA3 in
      combination with serum PSA and other clinical information enhances the diagnostic
      accuracy of prostate cancer detection and will enable physicians to make more
      informed decisions with patients at risk for prostate cancer.

PMID- 21093149
TI  - Potential of thermal treatment for decontamination of mercury containing wastes
      from chlor-alkali industry.
AB  - Old dumps of mercury waste sludges from chlor-alkaline industry are an
      environmental threat if not properly secured. Thermal retortion can be used to
      remove mercury from such wastes. This treatment reduces the total mercury
      content, and also may reduce the leachability of the residual mercury. The
      effects of treatment temperature and treatment time on both residual mercury
      levels and mercury leachability according to the US EPA TCLP leaching procedure,
      were investigated. Treatment for 1h at 800 degrees C allowed to quantitatively
      remove the mercury. Treatment at 400 degrees C and above allowed to decrease the
      leachable Hg contents to below the US EPA regulations. The ultimate choice of
      treatment conditions will depend on requirements of further handling options and
      cost considerations.

PMID- 21093150
TI  - Enhancing the electrochemical Cr(VI) reduction in aqueous solution.
AB  - In this study we present the cathodic Cr(VI) reduction using electrodissolution
      of iron anode. In batch experiments we tested four different cathodic materials;
      the best conditions were found when copper was used. It is observed that when
      more current is applied into the electrochemical cell faster reduction rates are
      achieved. Continuous experiments also reveal that Cr(VI) reduction could be done
      in a very efficient way. To confirm the experimental data, cyclic voltammetry was
      used and it was found that the cathodic Cr(VI) reduction is taking place.

PMID- 21093151
TI  - Strategies for processing diffraction data from randomly oriented particles.
AB  - The high intensity of free-electron X-ray light sources may enable structure
      determinations of viruses or even individual proteins without the encumbrance of
      first forming crystals. This note compares two schemes of non-crystalline
      diffraction data collection that have been proposed: serial single-shot data from
      individual particles, and averaged cross-correlation data from particle
      ensembles. The information content of these schemes is easily compared and we
      show that the single-shot approach, although experimentally more challenging, is
      always superior in this respect. In fact, for 3D structure determination a
      constraint counting argument shows that the cross-correlation scheme suffers from
      data deficiency.

PMID- 21093152
TI  - Bright-field scanning confocal electron microscopy using a double aberration
      corrected transmission electron microscope.
AB  - Scanning confocal electron microscopy (SCEM) offers a mechanism for three
      dimensional imaging of materials, which makes use of the reduced depth of field
      in an aberration-corrected transmission electron microscope. The simplest
      configuration of SCEM is the bright-field mode. In this paper we present
      experimental data and simulations showing the form of bright-field SCEM images.
      We show that the depth dependence of the three-dimensional image can be explained
      in terms of two-dimensional images formed in the detector plane. For a
      crystalline sample, this so-called probe image is shown to be similar to a
      conventional diffraction pattern. Experimental results and simulations show how
      the diffracted probes in this image are elongated in thicker crystals and the use
      of this elongation to estimate sample thickness is explored.

PMID- 21093153
TI  - Effect of vitamin E supplementation on naturally acquired parasitic infection in
      lambs.
AB  - Gastrointestinal nematode infections cause substantial economic losses in pasture
      based sheep farming worldwide. Host nutritional status has been identified as a
      key component of immune function. While vitamin E supplementation is known to
      have broad-spectrum effects on immune function in livestock, to our knowledge,
      there are no reports on the effect of vitamin E supplementation on
      trichostrongylid parasite infections in lambs. This study evaluated the effect of
      parenteral vitamin E supplementation on naturally acquired parasite infection in
      lambs. Twenty-seven spring lambs were sequentially assigned to receive injections
      of vitamin E (15 or 30 IU D-alpha-tocopherol/kg body weight (BW) or placebo,
      every two weeks, from birth to 28 weeks of age. Blood was collected at weeks 0,
      2, 4, 8, 12, 16, 20, 24, and 28 to determine serum alpha-tocopherol
      concentration. Once the youngest animal reached 15 weeks of age all lambs were
      dewormed and grazed together on a pasture known to be contaminated with
      trichostrongylid larvae. Fecal egg count and blood packed cell volume (%) were
      determined on each lamb immediately prior to deworming and for the first seven
      weeks of pasture infection. Lambs were euthanized when they reached 28 weeks of
      age for determination of parasite worm burdens. Vitamin E supplementation at 30
      IU/kg BW increased serum alpha-tocopherol over that of placebo (P<0.001) however,
      there was no effect of vitamin E supplementation on liver (P=0.804) or muscle
      (P=0.16) alpha-tocopherol content. There was no effect of vitamin E
      supplementation on fecal egg counts, packed cell volume, worm burden or nematode
      species distribution. Nematode genera identified were Haemonchus (30%),
      Trichostrongylus (42%), Nematodirus (27%), Strongyloides sp. (<1%), and
      Aonchotheca sp. (<1%). These results indicate that biweekly injections of vitamin
      E at 15 and 30 IU d-alpha-tocopherol/kg BW, had no effect on parasitological
      parameters used in the study to assess gastrointestinal nematode infection.

PMID- 21093155
TI  - Isolation and identification of a South China strain of Plasmodium inui from
      Macaca fascicularis.
AB  - Southeast Asian macaques are hosts of a number of Plasmodium infections, some of
      which are transmittable to humans. During examination of blood films of five wild
      caught long-tailed macaques Macaca fascicularis from South China, malaria
      infection was detected in one of the monkeys. In order to isolate this parasite
      for identification and characterization, we experimentally passed this parasite
      through both Assamese (M. assamensis) and rhesus (M. mulatta) monkeys by
      intravenous injection of infected blood. This parasite morphologically resembled
      Plasmodium inui, and had a typical 72 h quartan periodicity. This parasite was
      infective to Anopheles dirus mosquitoes, and salivary gland sporozoites appeared
      13 days post feeding. Feeding by 20 infected An. dirus mosquitoes on another
      Assamese monkey produced infection with a prepatent period of 8 days. Molecular
      analysis of the small subunit rRNA genes and the mitochondrial genome confirmed
      this parasite as an isolate of P. inui. In spleen-intact macaques, the infection
      had a protracted duration with parasites being detected during the rearing of the
      infected monkeys for over two years. In summary, this study identified a P. inui
      isolate and successfully passed this parasite through Assamese monkeys by both
      intravenous inoculation and mosquito transmission.

PMID- 21093154
TI  - Prevalence of intestinal parasites and genotyping of Giardia intestinalis in pet
      shop puppies in east Japan.
AB  - The current study examined the prevalence of intestinal parasites and genotypes
      of Giardia intestinalis in puppies from nine pet shops in east Japan. Fresh fecal
      samples from 1794 puppies (?3 months old) were collected on one occasion. Giardia
      spp. was examined for specific coproantigen using ELISA kit (SNAP(r)Giardia,
      IDEXX Laboratories, Inc., USA). Other intestinal parasites were detected
      microscopically using the formalin-ethyl acetate sedimentation technique.
      Genotyping was determined for the random 29 stool samples identified as Giardia
      spp. positive using PCR and direct sequencing of the glutamate dehydrogenase
      (gdh) gene. Overall prevalence of protozoan Giardia spp. and Cystoisospora spp.
      revealed 23.4% and 11.3%, respectively. Prevalence of ascarids, Strongyloides
      spp. and hookworms were recorded 1.8%, 1.1% and 0.1%, respectively. Protozoan
      Giardia spp. and Cystoisospora spp., thus, represent important pathogens among
      pet shop puppies. All genotyped G. intestinalis isolates were belonged to
      assemblage C or D, identified as dog-specific genotypes. Zoonotic assemblage A
      and B were not demonstrated. The result suggests that the risk of zoonotic
      transmission of G. intestinalis from pet shops puppies to humans may be quite low
      in Japan.

PMID- 21093156
TI  - Standardisation of a coproantigen reduction test (CRT) protocol for the diagnosis
      of resistance to triclabendazole in Fasciola hepatica.
AB  - A sheep trial was performed to standardise a coproantigen reduction test (CRT)
      protocol for the diagnosis of resistance to triclabendazole (TCBZ) in Fasciola
      hepatica). The CRT employs the BIO K201 Fasciola coproantigen ELISA (Bio-X
      Diagnostics, Jemelle, Belgium) to test for the presence of F. hepatica
      coproantigens in a faecal sample. If it is coproantigen-positive, the CRT
      protocol recommends that faecal samples are re-tested for coproantigens at 14
      days post-treatment (dpt), with negative testing at this point indicating TCBZ
      success. Initial work aimed to confirm the sensitivity of the BIO K201 ELISA for
      Fasciola infection and investigate whether coproantigens represent a robust
      reduction marker of TCBZ efficacy. Thirty-eight, indoor-reared sheep were
      artificially infected with F. hepatica isolates known to be susceptible
      (Cullompton) and resistant (Sligo) to TCBZ action, respectively. Treatment was
      administered at 12 weeks post-infection (wpi), with 2 sheep groups, infected with
      each isolate, culled at 2 and 4 weeks post-treatment (wpt), respectively.
      Necropsy was performed to confirm treatment efficacy. Individual faecal samples
      were collected twice-weekly throughout the trial period. Additional work focused
      on the effect of temperature on faecal sample collection and storage. Faecal
      samples collected from sheep positive for F. hepatica infection were sub-sampled
      and left at room temperature. Individual sub-samples were tested by ELISA on
      consecutive days and these readings compared to the original test result on the
      day of collection. In addition, ELISA values were compared between faecal sub
      samples prepared on the day of sampling and post storage at -20 degrees C. Also,
      an immunocytochemical study was performed to determine the tissue site of origin
      of the coproantigen protein in the fluke. Results showed that the BIO K201 ELISA
      was sensitive for Fasciola coproantigens, with coproantigens detectable from 5
      wpi onwards. The suitability of coproantigens as a diagnostic marker of TCBZ
      efficacy was supported by the absence and presence of coproantigens in TCBZ
      treated Cullompton (TCBZ-susceptible) and Sligo (TCBZ-resistant) F. hepatica
      infections at 2 and 4 wpt, respectively. Study results suggest that low to
      moderate temperature has little, if any, impact on coproantigen stability in
      faecal samples, but that higher temperatures may have. Immunolabelling for the
      coproantigen showed that it was specific to the gastrodermal cells of both adult
      and juvenile flukes.

PMID- 21093157
TI  - Epidemiology of canine heartworm in its southern distribution limit in South
      America: Risk factors, inter-annual trend and spatial patterns.
AB  - This study was aimed at understanding some aspects of the canine heartworm
      epidemiology in the southern distribution limit of the parasite in South America.
      With this objective, 19,298 blood samples of owned dogs from 65 localities of 13
      municipalities of Buenos Aires Province were tested for Dirofilaria immitis
      circulating microfilariae and/or female antigens. The overall heartworm
      prevalence was 1.63% by microhematocrit tube technique (n=19,136), 3.65% by
      modified Knott (n=713), and 14.41% by antigen test kit (n=118). Microfilaremic
      dogs showed a median of 1933 microfilariae per millilitre (q1=375, q3=5625,
      n=100). Male dogs belonging to breeds of short hair and large size recorded
      significantly higher prevalences than the other categories. Also, the prevalence
      increased significantly with the age and only dogs younger than 12 months were
      not found infected. A clear decreasing trend of the annual prevalence was
      observed during the whole study period, from 3.91% in 2001 to 1.17% in 2006. D.
      immitis-infected dogs were detected in 32 localities of 9 municipalities
      (prevalence range: 0.2-6.7%). Generalized linear models were used to assess
      associations between heartworm prevalence and environmental variables. The
      resulting significant models were univariate and included variables related with
      soil cover and human population density. The best model predicted maximum
      heartworm prevalences around middle values of bare soil cover, and lower at high
      and low covers. According to our analyses, canine heartworm infection in urban
      temperate Argentina could be described as relatively low, endemic, and spatially
      heterogeneous. Host and environmental factors affecting heartworm transmission at
      local level were identified and discussed.

PMID- 21093158
TI  - Differential effect of amphetamine on c-fos expression in female aromatase
      knockout (ArKO) mice compared to wildtype controls.
AB  - Estrogen may be involved in psychosis by an interaction with central dopaminergic
      activity. Aromatase knockout mice are unable to produce estrogen and have been
      shown to display altered behavioural responses and effects of the dopamine
      releaser, amphetamine. This study investigates the effect of gonadal status on
      amphetamine-induced c-fos expression in the brains of female aromatase knockout
      and wildtype mice. Six groups of mice were treated intraperitoneally with saline
      or 5mg/kg amphetamine. Fos immunoreactivity was assessed in the cingulate cortex,
      caudate putamen and nucleus accumbens. Aromatase knockout mice showed markedly
      reduced amphetamine-induced Fos immunoreactivity compared to wildtype mice.
      However, the amphetamine response was restored in aromatase-knockout mice after
      ovariectomy, which reduced this effect in wildtype controls. Estrogen
      supplementation reversed the effect of ovariectomy in wildtype mice but had no
      additional significant effect in aromatase-knockout mice. These results indicate
      that mechanisms involved in amphetamine-induced c-fos expression are altered in
      aromatase knockout mice and that the primary hormone involved in this effect is
      not estrogen, but may be another factor released from the ovaries, such as an
      androgen. These results provide new insight into the effect of gonadal hormones
      on amphetamine induced c-fos expression in this mouse model of estrogen
      deficiency. These results could be important for our understanding of the role of
      sex steroid hormones in psychosis.

PMID- 21093159
TI  - FPGS gene is a novel causative gene for cleft lip in China.
AB  - In China, patients with cleft lip tend to be blood group A. Thus, blood group A
      gene can be viewed as a marker gene for cleft lip. Based on the principle of
      linkage analysis, we may find a causative gene for cleft lip near blood group A
      gene. Among those genes that flank blood group A gene, FPGS gene, only 5.5 cM
      apart from blood group A gene, is suspected to be a good candidate causative gene
      for cleft lip. A normal FPGS gene plays an essential role in intracellular folate
      homeostasis and metabolism, while a variant FPGS gene would lead to folate
      disturbances or even folate deficiency. Since folate deficiency has been
      documented to contribute to cleft lip, the resulting folate deficiency induced by
      a variant FPGS gene would contribute to cleft lip, further strengthening that
      FPGS gene is a good candidate causative gene for cleft lip. We therefore propose
      FPGS gene as a novel causative gene for cleft lip.

PMID- 21093160
TI  - A novel promising therapy for skin aging: dermal multipotent stem cells against
      photoaged skin by activation of TGF-beta/Smad and p38 MAPK signaling pathway.
AB  - Skin photoaging, the most common skin damage, is caused by chronic UV
      irradiation. It is involved in the reduction, aging and apoptosis of fibroblasts
      (FBs) as well as the blockage of transforming growth factor-beta (TGF-beta)/Smad
      and p38 mitogen-actived protein kinase (MAPK) signaling pathways. Dermal
      multipotent stem cells (dMSCs) are a population of adult stem cells derived from
      dermis in recent years. It has been confirmed that dMSCs can activate or
      differentiate into FBs to participate in wound healing by producing and
      expressing TGF-beta and other cytokines. Considering the mechanism of skin
      photoaging and the role of dMSCs, we hold a hypothesis that dMSCs may be applied
      in skin photoaging by activating TGF-beta/Smad and p38 MAPK signaling pathways,
      and then stimulating FBs to secrete and synthesize collagen or elastin,
      heightening the extracellular matrix, finally eliminating wrinkles and
      strengthening skin elasticity. These would provide a novel approach for anti-skin
      photoaging.

PMID- 21093161
TI  - Crude lipoxygenase from pig muscle: partial characterization and interactions of
      temperature, NaCl and pH on its activity.
AB  - Crude lipoxygenase (LOX) was extracted from fresh pig bacon belly and studied of
      partial characteristics. The interactions of temperature, sodium chloride (NaCl)
      and pH on LOX activity were investigated by response surface methodology (RSM).
      Kinetic studies indicated that the Michaelis constant (K(m)) and maximum velocity
      (V(max)) for LOX activity using linoleic acid as substrate were 68 MUM and 0.26
      U/min at 20 degrees C, respectively. The optimal conditions for this reaction
      were: substrate concentration 3.47 mM, reaction temperature 39 degrees C and pH
      ?9.0. The NaCl critical value for LOX activity was 3.0% (w/w) at 20 degrees C,
      above which the LOX activity began to decrease. Temperature had significant
      interactions (p<0.05) with NaCl and pH. The temperature critical value decreased
      with NaCl content increasing, while increased with pH increasing. These indicated
      that LOX activity and enzyme-catalyzed lipid oxidation in dry-cured meat products
      could be regulated by controlling process factors during the processing.

PMID- 21093162
TI  - Evaluation of vascular endothelial growth factor as a prognostic marker for local
      relapse in early-stage breast cancer patients treated with breast-conserving
      therapy.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is an important protein
      involved in the process of angiogenesis that has been found to correlate with
      relapse-free and overall survival in breast cancer, predominantly in locally
      advanced and metastatic disease. A paucity of data is available on the prognostic
      implications of VEGF in early-stage breast cancer; specifically, its prognostic
      value for local relapse after breast-conserving therapy (BCT) is largely unknown.
      The purpose of our study was to assess VEGF expression in a cohort of early-stage
      breast cancer patients treated with BCT and to correlate the clinical and
      pathologic features and outcomes with overexpression of VEGF. METHODS AND
      MATERIALS: After obtaining institutional review board approval, the paraffin
      specimens of 368 patients with early-stage breast cancer treated with BCT between
      1975 and 2005 were constructed into tissue microarrays with twofold redundancy.
      The tissue microarrays were stained for VEGF and read by a trained pathologist,
      who was unaware of the clinical details, as positive or negative according the
      standard guidelines. The clinical and pathologic data, long-term outcomes, and
      results of VEGF staining were analyzed. RESULTS: The median follow-up for the
      entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368
      patients. Although VEGF expression did not correlate with age at diagnosis, tumor
      size, nodal status, histologic type, family history, estrogen
      receptor/progesterone receptor status, or HER-2 status, a trend was seen toward
      increased VEGF expression in the black cohort (26% black vs. 13% white, p=.068).
      Within the margin-negative cohort, VEGF did not predict for local relapse-free
      survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free
      survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p>.05).
      Subset analysis revealed that VEGF was highly predictive of local RFS in node
      positive, margin-negative patients (86% vs. 100%, p=.029) on univariate analysis,
      but it did not retain its significance on multivariate analysis (hazard ratio,
      2.52; 95% confidence interval, 0.804-7.920, p=.113). No other subgroups were
      identified in which a correlation was found between VEGF expression and local
      relapse. CONCLUSION: To our knowledge, our study is the first to assess the
      prognostic value of VEGF with the endpoint of local relapse in early-stage breast
      cancer treated with BCT, an important question given the recent increased use of
      targeted antiangiogenic agents in early-stage breast cancer. Our study results
      suggest that VEGF is not an independent predictor of local RFS after BCT, but
      additional, larger studies specifically analyzing the endpoint of VEGF and local
      relapse are warranted.

PMID- 21093163
TI  - MicroRNA regulation of ionizing radiation-induced premature senescence.
AB  - PURPOSE: MicroRNAs (miRNAs) have emerged as critical regulators of many cellular
      pathways. Ionizing radiation (IR) exposure causes DNA damage and induces
      premature senescence. However, the role of miRNAs in IR-induced senescence has
      not been well defined. Thus, the purpose of this study was to identify and
      characterize senescence-associated miRNAs (SA-miRNAs) and to investigate the role
      of SA-miRNAs in IR-induced senescence. METHODS AND MATERIALS: In human lung (WI
      38) fibroblasts, premature senescence was induced either by IR or busulfan (BU)
      treatment, and replicative senescence was accomplished by serial passaging. MiRNA
      microarray were used to identify SA-miRNAs, and real-time reverse transcription
      (RT)-PCR validated the expression profiles of SA-miRNAs in various senescent
      cells. The role of SA-miRNAs in IR-induced senescence was characterized by
      knockdown of miRNA expression, using anti-miRNA oligonucleotides or by miRNA
      overexpression through the transfection of pre-miRNA mimics. RESULTS: We
      identified eight SA-miRNAs, four of which were up-regulated (miR-152, -410, -431,
      and -493) and four which were down-regulated (miR-155, -20a, -25, and -15a), that
      are differentially expressed in both prematurely senescent (induced by IR or BU)
      and replicatively senescent WI-38 cells. Validation of the expression of these SA
      miRNAs indicated that down-regulation of miR-155, -20a, -25, and -15a is a
      characteristic miRNA expression signature of cellular senescence. Functional
      analyses revealed that knockdown of miR-155 or miR-20a, but not miR-25 or miR
      15a, markedly enhanced IR-induced senescence, whereas ectopic overexpression of
      miR-155 or miR-20a significantly inhibited senescence induction. Furthermore, our
      studies indicate that miR-155 modulates IR-induced senescence by acting
      downstream of the p53 and p38 mitogen-activated protein kinase (MAPK) pathways
      and in part via regulating tumor protein 53-induced nuclear protein 1 (TP53INP1)
      expression. CONCLUSION: Our results suggest that SA-miRNAs are involved in the
      regulation of IR-induced senescence, so targeting these miRNAs may be a novel
      approach for modulating cellular response to radiation exposure.

PMID- 21093164
TI  - Early outcomes from three prospective trials of image-guided proton therapy for
      prostate cancer.
AB  - PURPOSE: To report early outcomes with image-guided proton therapy for prostate
      cancer. METHODS AND MATERIALS: We accrued 211 prostate cancer patients on
      prospective Institutional Review Board-approved trials of 78 cobalt gray
      equivalent (CGE) in 39 fractions for low-risk disease, dose escalation from 78 to
      82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel
      followed by androgen deprivation for high-risk disease. Minimum follow-up was 2
      years. RESULTS: One intermediate-risk patient and 2 high-risk patients had
      disease progression. Pretreatment genitourinary (GU) symptom management was
      required in 38% of patients. A cumulative 88 (42%) patients required
      posttreatment GU symptom management. Four transient Grade 3 GU toxicities
      occurred, all among patients requiring pretreatment GU symptom management.
      Multivariate analysis showed correlation between posttreatment GU 2+ symptoms and
      pretreatment GU symptom management (p < 0.0001) and age (p = 0.0048). Only 1
      Grade 3+ gastrointestinal (GI) symptom occurred. The prevalence of Grade 2+ GI
      symptoms was 0 (0%), 10 (5%), 12 (6%), and 8 (4%) at 6, 12, 18, and 24 months,
      with a cumulative incidence of 20 (10%) patients at 2 years after proton therapy.
      Univariate and multivariate analyses showed significant correlation between Grade
      2+ rectal bleeding and proctitis and the percentage of rectal wall (rectum)
      receiving doses ranging from 40 CGE (10 CGE) to 80 CGE. CONCLUSIONS: Early
      outcomes with image-guided proton therapy suggest high efficacy and minimal
      toxicity with only 1.9% Grade 3 GU symptoms and <0.5% Grade 3 GI toxicities.

PMID- 21093165
TI  - Rapid automated treatment planning process to select breast cancer patients for
      active breathing control to achieve cardiac dose reduction.
AB  - PURPOSE: To evaluate a rapid automated treatment planning process for the
      selection of patients with left-sided breast cancer for a moderate deep
      inspiration breath-hold (mDIBH) technique using active breathing control (ABC);
      and to determine the dose reduction to the left anterior descending coronary
      artery (LAD) and the heart using mDIBH. METHOD AND MATERIALS: Treatment plans
      were generated using an automated method for patients undergoing left-sided
      breast radiotherapy (n = 53) with two-field tangential intensity-modulated
      radiotherapy. All patients with unfavorable cardiac anatomy, defined as having
      >10 cm(3) of the heart receiving 50% of the prescribed dose (V(50)) on the free
      breathing automated treatment plan, underwent repeat scanning on a protocol using
      a mDIBH technique and ABC. The doses to the LAD and heart were compared between
      the free-breathing and mDIBH plans. RESULTS: The automated planning process
      required approximately 9 min to generate a breast intensity-modulated
      radiotherapy plan. Using the dose-volume criteria, 20 of the 53 patients were
      selected for ABC. Significant differences were found between the free-breathing
      and mDIBH plans for the heart V(50) (29.9 vs. 3.7 cm(3)), mean heart dose (317
      vs. 132 cGy), mean LAD dose (2,047 vs. 594 cGy), and maximal dose to 0.2 cm(3) of
      the LAD (4,155 vs. 1,507 cGy, all p <.001). Of the 17 patients who had a breath
      hold threshold of >= 0.8 L, 14 achieved a >= 90% reduction in the heart V(50)
      using the mDIBH technique. The 3 patients who had had a breath-hold threshold
      <0.8 L achieved a lower, but still significant, reduction in the heart V(50).
      CONCLUSIONS: A rapid automated treatment planning process can be used to select
      patients who will benefit most from mDIBH. For selected patients with unfavorable
      cardiac anatomy, the mDIBH technique using ABC can significantly reduce the dose
      to the LAD and heart, potentially reducing the cardiac risks.

PMID- 21093166
TI  - Preoperative single fraction partial breast radiotherapy for early-stage breast
      cancer.
AB  - PURPOSE: Several recent series evaluating external beam accelerated partial
      breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly
      related to large volumes of normal tissue receiving near-prescription doses. We
      hypothesized that delivery of external beam PBI in a single fraction to the
      preoperative tumor volume would be feasible and result in a decreased dose to the
      uninvolved breast compared with institutional postoperative PBI historical
      controls. METHODS AND MATERIALS: A total of 17 patients with unifocal Stage T1
      breast cancer were identified. Contrast-enhanced subtraction magnetic resonance
      images were loaded into an Eclipse treatment planning system and used to define
      the target volumes. A "virtual plan" was created using four photon beams in a
      noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning
      target volume. RESULTS: The median breast volume was 1,713 cm(3) (range: 1,014
      2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all
      cases, 100% of the prescription dose covered 95% of the clinical target volume.
      The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of
      the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was
      3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42)
      and 53% (range: 24-65) in the institutional historical controls treated with
      postoperative external beam PBI (p = .002). The median maximum skin dose was 9
      Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to
      the heart and ipsilateral lung were negligible. CONCLUSION: Preoperative PBI
      resulted in a substantial reduction in ipsilateral breast tissue dose compared
      with postoperative PBI. The skin dose appeared reasonable, given the small
      volumes. A prospective Phase I trial evaluating this technique is ongoing.

PMID- 21093168
TI  - Patient-specific 3D pretreatment and potential 3D online dose verification of
      Monte Carlo-calculated IMRT prostate treatment plans.
AB  - PURPOSE: Fast and reliable comprehensive quality assurance tools are required to
      validate the safety and accuracy of complex intensity-modulated radiotherapy
      (IMRT) plans for prostate treatment. In this study, we evaluated the performance
      of the COMPASS system for both off-line and potential online procedures for the
      verification of IMRT treatment plans. METHODS AND MATERIALS: COMPASS has a
      dedicated beam model and dose engine, it can reconstruct three-dimensional dose
      distributions on the patient anatomy based on measured fluences using either the
      MatriXX two-dimensional (2D) array (offline) or a 2D transmission detector (T2D)
      (online). For benchmarking the COMPASS dose calculation, various dose-volume
      indices were compared against Monte Carlo-calculated dose distributions for five
      prostate patient treatment plans. Gamma index evaluation and absolute point dose
      measurements were also performed in an inhomogeneous pelvis phantom using
      extended dose range films and ion chamber for five additional treatment plans.
      RESULTS: MatriXX-based dose reconstruction showed excellent agreement with the
      ion chamber (<0.5%, except for one treatment plan, which showed 1.5%), film
      (~100% pixels passing gamma criteria 3%/3 mm) and mean dose-volume indices (<2%).
      The T2D based dose reconstruction showed good agreement as well with ion chamber
      (<2%), film (~99% pixels passing gamma criteria 3%/3 mm), and mean dose-volume
      indices (<5.5%). CONCLUSION: The COMPASS system qualifies for routine prostate
      IMRT pretreatment verification with the MatriXX detector and has the potential
      for on-line verification of treatment delivery using T2D.

PMID- 21093167
TI  - Jaw dysfunction related to pterygoid and masseter muscle dosimetry after
      radiation therapy in children and young adults with head-and-neck sarcomas.
AB  - PURPOSE: To investigate the relationship between jaw function, patient and
      treatment variables, and radiation dosimetry of the mandibular muscles and joints
      in children and young adults receiving radiation for soft-tissue and bone
      sarcomas. METHODS AND MATERIALS: Twenty-four pediatric and young adult patients
      with head-and-neck sarcomas were treated on an institutional review board
      approved prospective study of focal radiation therapy for local tumor control.
      Serial jaw depression measurements were related to radiation dosimetry delivered
      to the medial and lateral pterygoid muscles, masseter muscles, and
      temporomandibular joints to generate mathematical models of jaw function.
      RESULTS: Baseline jaw depression was only influenced by the degree of surgical
      resection. In the first 12 weeks from initiation of radiation, surgical
      procedures greater than a biopsy, administration of cyclophosphamide containing
      chemotherapy regimes, and large gross tumor volumes adversely affected jaw
      depression. Increasing dose to the pterygoid and masseter muscles above 40 Gy
      predicted loss of jaw function over the full course of follow-up. CONCLUSIONS:
      Clinical and treatment factors are related to initial and subsequent jaw
      dysfunction. Understanding these complex interactions and the affect of specific
      radiation doses may help reduce the risk for jaw dysfunction in future children
      and young adults undergoing radiation therapy for the management of soft-tissue
      and bone sarcomas.

PMID- 21093169
TI  - Radiation enhances regulatory T cell representation.
AB  - PURPOSE: Immunotherapy could be a useful adjunct to standard cytotoxic therapies
      such as radiation in patients with micrometastatic disease, although successful
      integration of immunotherapy into treatment protocols will require further
      understanding of how standard therapies affect the generation of antitumor immune
      responses. This study was undertaken to evaluate the impact of radiation therapy
      (RT) on immunosuppressive T regulatory (Treg) cells. METHODS AND MATERIALS: Treg
      cells were identified as a CD4(+)CD25(hi)Foxp3(+) lymphocyte subset, and their
      fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and
      without RT. RESULTS: CD4(+)CD25(hi)Foxp3(+) Treg cells increased in immune organs
      after local leg or whole-body radiation. A large part, but not all, of this
      increase after leg-only irradiation could be ascribed to radiation scatter and
      Treg cells being intrinsically more radiation resistant than other lymphocyte
      subpopulations, resulting in their selection. Their functional activity on a per
      cell basis was not affected by radiation exposure. Similar findings were made
      with mice receiving local RT to murine prostate tumors growing in the leg. The
      importance of the Treg cell population in the response to RT was shown by
      systemic elimination of Treg cells, which greatly enhanced radiation-induced
      tumor regression. CONCLUSIONS: We conclude that Treg cells are more resistant to
      radiation than other lymphocytes, resulting in their preferential increase. Treg
      cells may form an important homeostatic mechanism for tissues injured by
      radiation, and in a tumor context, they may assist in immune evasion during
      therapy. Targeting this population may allow enhancement of radiotherapeutic
      benefit through immune modulation.

PMID- 21093170
TI  - Vaginal motion and bladder and rectal volumes during pelvic intensity-modulated
      radiation therapy after hysterectomy.
AB  - PURPOSE: To evaluate variations in bladder and rectal volume and the position of
      the vaginal vault during a 5-week course of pelvic intensity-modulated radiation
      therapy (IMRT) after hysterectomy. METHODS AND MATERIALS: Twenty-four patients
      were instructed how to fill their bladders before simulation and treatment. These
      patients underwent computed tomography simulations with full and empty bladders
      and then underwent rescanning twice weekly during IMRT; patients were asked to
      have full bladder for treatment. Bladder and rectal volumes and the positions of
      vaginal fiducial markers were determined, and changes in volume and position were
      calculated. RESULTS: The mean full and empty bladder volumes at simulation were
      480 cc (range, 122-1,052) and 155 cc (range, 49-371), respectively. Bladder
      volumes varied widely during IMRT: the median difference between the maximum and
      minimum volumes was 247 cc (range, 96-585). Variations in rectal volume during
      IMRT were less pronounced. For the 16 patients with vaginal fiducial markers in
      place throughout IMRT, the median maximum movement of the markers during IMRT was
      0.59 cm in the right-left direction (range, 0-0.9), 1.46 cm in the anterior
      posterior direction (range, 0.8-2.79), and 1.2 cm in the superior-inferior
      direction (range, 0.6-2.1). Large variations in rectal or bladder volume
      frequently correlated with significant displacement of the vaginal apex.
      CONCLUSION: Although treatment with a full bladder is usually preferred because
      of greater sparing of small bowel, our data demonstrate that even with detailed
      instruction, patients are unable to maintain consistent bladder filling.
      Variations in organ position during IMRT can result in marked changes in the
      position of the target volume and the volume of small bowel exposed to high doses
      of radiation.

PMID- 21093171
TI  - Perineural infiltration of cutaneous squamous cell carcinoma and basal cell
      carcinoma without clinical features.
AB  - PURPOSE: To review the factors that influence outcome and patterns of relapse in
      patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma
      (BCC) with perineural infiltration (PNI) without clinical or radiologic features,
      treated with surgery and radiotherapy. METHODS AND MATERIALS: Between 1991 and
      2004, 222 patients with SCC or BCC with PNI on pathologic examination but without
      clinical or radiologic PNI features were identified. Charts were reviewed
      retrospectively and relevant data collected. All patients were treated with
      curative intent; all had radiotherapy, and most had surgery. The primary endpoint
      was 5-year relapse-free survival from the time of diagnosis. RESULTS: Patients
      with SCC did significantly worse than those with BCC (5-year relapse-free
      survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence
      did significantly worse than de novo in terms of 5-year local failure (40% vs.
      19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was
      also a significant factor. Of the PNI-specific factors for SCC, focal PNI did
      significantly better than more-extensive PNI, but involved nerve diameter or
      presence of PNI at the periphery of the tumor were not significant factors.
      CONCLUSIONS: Radiotherapy in conjunction with surgery offers an acceptable
      outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is
      not an adverse feature.

PMID- 21093172
TI  - Clinical trials of a urethral dose measurement system in brachytherapy using
      scintillation detectors.
AB  - PURPOSE: To report on the clinical feasibility of a novel scintillation detector
      system with fiberoptic readout that measures the urethral dose during high-dose
      rate brachytherapy treatment of the prostate. METHODS AND MATERIALS: The clinical
      trial enrolled 24 patients receiving high-dose-rate brachytherapy treatment to
      the prostate. After the first 14 patients, three improvements were made to the
      dosimeter system design to improve clinical reliability: a dosimeter self
      checking facility; a radiopaque marker to determine the position of the
      dosimeter, and a more robust optical extension fiber. RESULTS: Improvements to
      the system design allowed for accurate dose measurements to be made in vivo. A
      maximum measured dose departure of 9% from the calculated dose was observed after
      dosimeter design improvements. CONCLUSIONS: Departures of the measured from the
      calculated dose, after improvements to the dosimetry system, arise primarily from
      small changes in patient anatomy. Therefore, we recommend that patient response
      be correlated with the measured in vivo dose rather than with the calculated
      dose.

PMID- 21093173
TI  - Should patient setup in lung cancer be based on the primary tumor? An analysis of
      tumor coverage and normal tissue dose using repeated positron emission
      tomography/computed tomography imaging.
AB  - PURPOSE: Evaluation of the dose distribution for lung cancer patients using a
      patient setup procedure based on the bony anatomy or the primary tumor. METHODS
      AND MATERIALS: For 39 patients with non-small-cell lung cancer, the planning
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)
      scan was registered to a repeated FDG-PET/CT scan made in the second week of
      treatment. Two patient setup methods were analyzed based on the bony anatomy or
      the primary tumor. The original treatment plan was copied to the repeated scan,
      and target and normal tissue structures were delineated. Dose distributions were
      analyzed using dose-volume histograms for the primary tumor, lymph nodes, lungs,
      and spinal cord. RESULTS: One patient showed decreased dose coverage of the
      primary tumor caused by progressive disease and required replanning to achieve
      adequate coverage. For the other patients, the minimum dose to the primary tumor
      did not significantly deviate from the planned dose: -0.2 +/- 1.7% (p = 0.71) and
      -0.1 +/- 1.7% (p = 0.85) for the bony anatomy setup and the primary tumor setup,
      respectively. For patients (n = 31) with nodal involvement, 10% showed a decrease
      in minimum dose larger than 5% for the bony anatomy setup and 13% for the primary
      tumor setup. The mean lung dose exceeded the maximum allowed 20 Gy in 21% of the
      patients for the bony anatomy setup and in 13% for the primary tumor setup,
      whereas for the spinal cord this occurred in 10% and 13% of the patients,
      respectively. CONCLUSIONS: In 10% and 13% of patients with nodal involvement,
      setup based on bony anatomy or primary tumor, respectively, led to important dose
      deviations in nodal target volumes. Overdosage of critical structures occurred in
      10-20% of the patients. In cases of progressive disease, repeated imaging
      revealed underdosage of the primary tumor. Development of practical ways for
      setup procedures based on repeated high-quality imaging of all tumor sites during
      radiotherapy should therefore be an important research focus.

PMID- 21093174
TI  - Predictive factors of tumor response after neoadjuvant chemoradiation for locally
      advanced rectal cancer.
AB  - PURPOSE: Neoadjuvant chemoradiation followed by surgery is the standard of care
      for locally advanced rectal cancer. The aim of this study was to correlate tumor
      response to survival and to identify predictive factors for tumor response after
      chemoradiation. METHODS AND MATERIALS: From 1998 to 2008, 168 patients with
      histologically proven locally advanced adenocarcinoma treated by preoperative
      chemoradiation before total mesorectal excision were retrospectively studied.
      They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)
      based chemotherapy. Analysis of tumor response was based on lowering of the T
      stage between pretreatment endorectal ultrasound and pathologic specimens.
      Overall and progression-free survival rates were correlated with tumor response.
      Tumor response was analyzed with predictive factors. RESULTS: The median follow
      up was 34 months. Five-year disease-free survival and overall survival rates
      were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively,
      in patients with pathological complete response, 38.6% and 71.9%, respectively,
      in patients with tumor downstaging, and 29.1 and 58.9% respectively, in patients
      with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of
      <5 ng/ml was significantly independently associated with pathologic complete
      tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04),
      pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with
      capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor
      downstaging. CONCLUSIONS: Downstaging and complete response after CRT improved
      progression-free survival and overall survival of locally advanced rectal
      adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml
      was associated with complete tumor response. Thus, small tumor size, a
      pretreatment CEA level of < 5 ng/ml, and use of capecitabine were associated with
      tumor downstaging.

PMID- 21093175
TI  - An ulnar intraneural ganglion arising from the pisotriquetral joint: case report.
AB  - Intraneural ganglions of the hand are rare and remain poorly understood. We
      report a case of an intraneural ganglion arising from the pisotriquetral joint
      that penetrated the ulnar nerve at Guyon's canal. Although rare, these ganglions
      should be considered in the differential diagnosis of any neoplasms causing
      compression neuropathy.

PMID- 21093176
TI  - Divergent fracture-dislocation of the hamatometacarpal joint: case report.
AB  - Hamatometacarpal fracture-dislocation is a rare injury that consists of a fourth
      metacarpal fracture and a fifth carpometacarpal joint injury. We present the case
      of a 21-year-old man with a divergent hamatometacarpal fracture-dislocation that
      consisted of a combination of dorsal intra-articular fracture-dislocation of the
      fourth carpometacarpal joint, palmar dislocation of the fifth carpometacarpal
      joint, and fracture of the hook of the hamate. The mechanism of palmar
      dislocation of the fifth metacarpal base and fracture of the hook of the hamate
      involved extension of the fifth metacarpal and ulnopalmar load transmission.

PMID- 21093177
TI  - Preoperative computer-assisted design templating of complex articular olecranon
      osteotomy: case report.
AB  - Preoperative 3-dimensional modeling methods are commonly used in orthopedic
      surgery but there have been limited reports of their use for planning upper
      extremity surgery. In this report, we describe a case of a malunited olecranon
      fracture and its management using custom preoperative computed tomographic
      templating and mechanical modeling. One year after surgery, the patient
      demonstrated nearly full painless restoration of function and motion.

PMID- 21093178
TI  - The role of the flexor carpi radialis muscle in scapholunate instability.
AB  - PURPOSE: The flexor carpi radialis (FCR) muscle has been suggested to act as a
      dynamic scaphoid stabilizer. Because the FCR tendon uses the scaphoid tuberosity
      as a pulley to reach its distal insertion onto the second metacarpal, it has been
      hypothesized that FCR muscle contraction generates a dorsally directed vector
      that resists the scaphoid from rotating into flexion. The purpose of the present
      study was to validate that hypothesis and clarify the role of the FCR as a
      dynamic scaphoid stabilizer. METHODS: Ten fresh cadaver wrist specimens were
      tested. A custom-designed testing apparatus was used to hold the forearm and
      wrist vertically, in neutral forearm rotation. A 6-degree-of-freedom,
      electromagnetic motion-tracking device, with sensors attached to the scaphoid,
      triquetrum, capitate, and radius, was used to monitor spatial changes in carpal
      alignment as a result of isometrically loading the FCR in 5 different wrist
      positions. RESULTS: In all specimens and all wrist positions, the scaphoid
      consistently rotated into flexion when the FCR was loaded. It also exhibited
      variable degrees of pronation or supination, depending on whether the wrist was
      in flexion or extension. When the wrist was loaded in neutral position, the
      scaphoid consistently supinated and the triquetrum pronated, these differences
      being statistically significant (p < .05). CONCLUSIONS: The scaphoid consistently
      rotated into flexion and supination when the FCR was loaded, while the triquetrum
      rotated in flexion and pronation. The positive effects of FCR muscle re-education
      in dynamic scapholunate instabilities can be explained not by this muscle's
      capability of extending the scaphoid, as has often been hypothesized, but by its
      ability to induce supination to the scaphoid and pronation to the triquetrum.
      Such opposite rotations are likely to result in a dorsal coaptation of the
      scapholunate joint with relaxation of the dorsal scapholunate ligament.

PMID- 21093179
TI  - Recurrent calcifying aponeurotic fibroma of the thumb: case report.
AB  - We present an unusual case report of an aggressive, recurrent calcifying
      aponeurotic fibroma of the thumb in an adult man with invasion into the distal
      and proximal phalanges, the skin, the radial and ulnar neurovascular bundles, and
      the tendons, treated with amputation and an immediate toe-to-thumb transfer.

PMID- 21093180
TI  - EMAS position statement: Bone densitometry screening for osteoporosis.
AB  - INTRODUCTION: Osteoporosis and its consequent fractures is a major public health
      problem. AIM: To formulate a position statement on the use of bone densitometry
      in screening postmenopausal women for osteoporosis and in their management.
      MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS
      AND CONCLUSIONS: Bone densitometry has an important role in screening
      postmenopausal women for osteoporosis. For higher sensitivity and specificity,
      there may be a stronger case for screening in later life, depending on the extent
      to which risk factors add to the value of bone mineral density tests.

PMID- 21093182
TI  - Bisphosphonates and oesophageal cancer risk: where are we now?

PMID- 21093181
TI  - 25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in
      postmenopausal women.
AB  - INTRODUCTION: Low 25-hydroxyvitamin D (25(OH) D) concentrations have been
      associated with radiologic worsening of osteoarthritis in some reports. However,
      the results are mixed and few studies have evaluated associations between 25(OH)
      D concentrations and both total vitamin D intake and clinical joint symptoms.
      STUDY DESIGN: Cross-sectional analyses of information from a subset of 1993
      postmenopausal women obtained at baseline entry in the Women's Health Initiative
      Calcium plus Vitamin D clinical trial. MAIN OUTCOME MEASURES: 25(OH) D
      concentration, total vitamin D intake (diet plus supplements), presence and
      severity of joint pain and joint swelling. RESULTS: The 25(OH) D levels were
      commonly low with 53% having deficient (<50 nmol/L) and only 17% having
      sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling
      (reported by 34%) were also commonly reported. 25(OH) D concentrations were
      modestly correlated with total vitamin D intake (R=0.29, p<0.0001); however,
      considerable variability in 25(OH) D concentrations for a given vitamin D intake
      was seen. In adjusted linear regression models, lower serum 25(OH) D
      concentrations were associated with higher average joint pain score (P=0.01 for
      trend) with differences most apparent in the lowest 25(OH) D levels sextile.
      CONCLUSIONS: Relatively low 25(OH) D levels and a high frequency of joint
      symptoms were common in this population of postmenopausal women. Total vitamin D
      intake was only modestly associated with 25(OH) D. Low serum 25(OH) D
      concentrations were associated with higher joint pain scores. These findings can
      inform the design of future intervention trials.

PMID- 21093183
TI  - Window resection of the trachea and secondary reconstruction for invasion by
      differentiated thyroid carcinoma.
AB  - OBJECTIVE: In cases of differentiated thyroid carcinoma, the presence or absence
      of invasion into the circumferential organs is an important prognostic factor.
      Surgical procedures include circular resection of the trachea with end-to-end
      anastomosis and window resection with secondary closure. We have used window
      resection with secondary closure since 1993, and herein retrospectively analyze
      the treatment outcomes for this surgical procedure in order to determine the
      indications for procedure selection. METHODS: Subjects comprised 41 cases of
      invasion by differentiated thyroid carcinoma into the trachea, for which surgery
      was performed at the Department of Head and Neck Surgery of the National Cancer
      Center Hospital East from 1993 to 2007. The mean age was 65.7+/-7.9 years, and
      the median length of the observation period was 43 months. There were 17 cases
      (41.4%) cases of secondary relapse. RESULTS: The 5-year and 10-year overall
      survival rates for this surgical procedure were 78.9% and 74.5%, respectively,
      while the 5-year and 10-year local control rates were 92.4% and 73.4%,
      respectively. The pathological resection stump was positive in 27 cases (65.8%),
      but no significant differences in treatment outcome were observed between the
      stump-positive group and the stump-negative group. There were 26 cases in which
      closure of the tracheal fistula was performed by the time of observation. When
      the tracheal defect had a diameter equivalent to 7 rings of the trachea or less
      and a circumference half that of the tracheal cartilage or smaller, including
      partial cricoid cartilage, it was possible to perform closure with only a local
      flap. For larger defects, reconstruction was performed using hard tissues or
      materials, such as hydroxyapatite, titanium mesh, and costal cartilage. There
      were 2 cases that required re-window because of dyspnea after closure.
      CONCLUSION: The treatment outcomes for this surgical procedure for invasive cases
      of differentiated thyroid carcinoma into the trachea resulted in a low rate of
      local recurrence and similar survival rates as described in other reports. Even
      for cases of resection exceeding half the circumference of the trachea, closure
      of the tracheal fistula can be performed using hard tissues or materials;
      however, in such cases, we believe that closure should be attempted progressively
      in a two-stage reconstruction.

PMID- 21093184
TI  - A familial case of LEOPARD syndrome associated with a high-functioning autism
      spectrum disorder.
AB  - A connection between LEOPARD syndrome (a rare autosomal dominant disorder) and
      autism spectrum disorders (ASDs) may exist. Of four related individuals (father
      and three sons) with LEOPARD syndrome, all patients exhibited clinical symptoms
      consistent with ASDs. Findings included aggressive behavior and impairment of
      social interaction, communication, and range of interests. The coexistence of
      LEOPARD syndrome and ASDs in the related individuals may be an incidental
      familial event or indicative that ASDs is associated with LEOPARD syndrome. There
      have been no other independent reports of the association of LEOPARD syndrome and
      ASDs. Molecular and biochemical mechanisms that may suggest a connection between
      LEOPARD syndrome and ASDs are discussed.

PMID- 21093186
TI  - [Need for public health].

PMID- 21093185
TI  - [Anomalous intraosseous venous drainage: a rare cause of pretibial varicose
      veins].
AB  - Valvular incompetence with reflux and postthrombotic syndrome are the most common
      features of varicose veins, a common disease. More rare etiologies must be evoked
      when these two main causes have been ruled out. We report herein the case of a 47
      year-old man who has been suffering from varicosis and complained with left leg
      pain since 15 years. He had already been managed by standard stripping, saphenous
      ligations, phlebectomies but was not completely relieved. X-ray findings of the
      tibia, doppler ultrasonography and magnetic resonance imaging led us to the
      diagnosis of tibial intraosseous venous drainage anomaly. We then report
      diagnosis and therapeutic decisional approach.

PMID- 21093187
TI  - [Kingella kingae spondylodiscitis in an adult].

PMID- 21093188
TI  - [Antibiotic susceptibility of Salmonella enterica serovar Typhi isolated from
      blood cultures at the Ain M'lila hospital (Algeria), between 2005 and 2008].
AB  - INTRODUCTION: Typhoid fever is a food- and water-borne disease, caused by
      Salmonella enterica serovar Typhi, responsible for high rates of morbidity and
      mortality in developing countries. Typhoid is also a public health problem in
      Algeria. Antimicrobial susceptibility surveillance must be applied to prevent the
      emergence of multidrug resistant strains. PATIENTS AND METHODS: We studied the
      incidence of S. enterica serovar Typhi isolated from blood cultures in the Ain
      M'lila public hospital (Algeria), between 2005 and 2008. Blood cultures were
      performed in the febrile stage of infection and positive samples were identified
      by biochemical and antigenic tests. Susceptibility to ampicillin, cotrimoxazole,
      chloramphenicol and nalidixic acid was tested by antibiogram. RESULTS: One
      hundred and seventy-eight strains were isolated from blood cultures between 2005
      and 2008. They were all susceptible to the antibiotics tested. DISCUSSION:
      Typhoid fever incidence has decreased in Algeria. In our region, it comes by
      outbreaks during the summer season, with no sporadic cases between the peaks. In
      our study, S. enterica serovar Typhi was still susceptible to antimicrobials
      despite the worldwide emergence of multidrug resistant strains. CONCLUSION: A
      regular surveillance of Salmonella typhi antibiotic susceptibility is mandatory.

PMID- 21093189
TI  - Ultrasound guided Core Biopsy, Fine Needle Aspiration Cytology and Surgical
      Excision Biopsy in the diagnosis of metastatic squamous cell carcinoma in the
      head and neck: an eleven year experience.
AB  - INTRODUCTION: This study aims to review our 11 year experience of diagnosing
      metastatic squamous cell carcinoma presenting as head and neck lumps. The
      techniques of Ultrasound guided Core Biopsy (USCB), Fine Needle Aspiration
      Cytology (FNAC) and Surgical Excision Biopsy (SEB) are compared. MATERIALS AND
      METHODS: All patients with metastatic squamous cell carcinoma (SCC) involving the
      lymph nodes of the head and neck or parotid gland, diagnosed at Eastbourne
      District General Hospital between January 1998 and November 2009 were identified.
      The following data items were collated: biopsy location (e.g. cervical lymph node
      or parotid), any history of likely primary SCC and site, type of biopsy used to
      establish a conclusive diagnosis (index diagnostic technique), previous biopsies,
      the technique and their results, subsequent histology results. RESULTS: A total
      of 90 patients were diagnosed with metastatic squamous cell carcinoma. The index
      diagnostic technique was USCB in 48 patients, FNAC in 29 and SEB in 13. In 72
      (80%) patients the index biopsy was the sole tissue sample taken prior to surgery
      or other treatment. The remaining 18 patients underwent a total of 22 previous
      biopsies prior to the index biopsy. 95% (21/22) of these previous biopsies were
      non-definitive FNAC and 5% (1/22) was a non-definitive USCB. FNACs also
      demonstrated the highest non-diagnostic rate (42%). The accuracy of USCB and FNAC
      in correlating with final histopathology was 97% and 85% respectively.
      CONCLUSIONS: USCB demonstrates excellent results in the diagnosis of metastatic
      SCC in the head and neck with higher accuracy and greater reliability than FNAC.

PMID- 21093190
TI  - Using multi-detector-row CT to diagnose ampullary adenoma or adenocarcinoma in
      situ.
AB  - OBJECTIVE: To assess the diagnostic accuracy of multi-detector-row computed
      tomography (MDCT) for the detection of ampullary adenomas or adenocarcinomas in
      situ. MATERIALS AND METHODS: We retrospectively reviewed 21 computed tomography
      (CT) images from 20 patients with ampullary tumors, and 22 CT images from 22
      patients without periampullary tumor. Three radiologists blindly and
      independently reviewed CT images. The sensitivities and specificities for
      identification of ampullary masses were calculated in all cases and in cases with
      adequate duodenal distension. The sensitivities and specificities for the
      diagnosis of ampullary tumors were calculated using the following criteria:
      identification of mass alone; presence of extrahepatic bile duct (EBD) dilation
      or identification of mass; presence of pancreatic duct (PD) dilation or
      identification of mass. Paired t-tests were performed to assess differences in
      mean values. RESULTS: The mean sensitivity and specificity of MDCT for the
      detection of an ampullary mass in all cases were 47.6% and 86.4%, and in cases
      with adequate duodenal distension, 66.7% (p=0.07) and 80.5% (p=0.32),
      respectively. When the presence of EBD dilation or identification of mass were
      used as criteria, the mean sensitivity and specificity were 73.0% (p=0.03) and
      60.6% (p=0.03), respectively. When presence of PD dilation or identification of
      mass were used as criteria, the mean sensitivity and specificity were 47.6% and
      81.8% (p=0.23). CONCLUSIONS: MDCT is moderately accurate for the diagnosis of
      ampullary adenoma or adenocarcinoma in situ. When EBD dilation or identification
      of mass were used as criteria, the sensitivity can be improved.

PMID- 21093191
TI  - A pilot study on potency determination of human follicle-stimulating hormone: a
      comparison between reversed-phase high-performance liquid chromatography method
      and the in vivo bioassay.
AB  - Reversed-phase high-performance liquid chromatography (RP-HPLC) was compared with
      the classical Steelman-Pohley bioassay (BA), based on animal use, for the
      determination of human follicle-stimulating hormone (hFSH) biological activity. A
      linear relationship (BA(IU)=0.9925 RP-HPLC(IU)-1.3165) with a highly significant
      correlation (r=0.9371; p<0.0001; n=24) was found for these two methods for six
      hFSH preparations of different origins. The mean difference between the
      bioactivity predicted from RP-HPLC data via this equation and the mean of the
      bioactivities obtained with the two methods for six other hFSH preparations was 
      1.4%, with a 95% confidence interval of -9.3 to +6.6%. The precision of these
      parameters was 1.63% and 2.82%, respectively. These results demonstrate that RP
      HPLC is a viable physical-chemical alternative to the use of an in vivo bioassay
      for hFSH potency determination, applicable also to hFSH Standards containing
      large amounts of human serum albumin.

PMID- 21093192
TI  - Necrotizing fasciitis in the setting of marine injury.

PMID- 21093193
TI  - Counseling women with early pregnancy failure: utilizing evidence, preserving
      preference.
AB  - OBJECTIVES: To apply principles of shared decision-making to EPF management
      counseling. To present a patient treatment priority checklist developed from
      review of available literature on patient priorities for EPF management. METHODS:
      Review of evidence for patient preferences; personal, emotional, physical and
      clinical factors that may influence patient priorities for EPF management; and
      the clinical factors, resources, and provider bias that may influence current
      practice. RESULTS: Women have strong and diverse preferences for EPF management
      and report higher satisfaction when treated according to these preferences.
      However, estimates of actual treatment patterns suggest that current practice
      does not reflect the evidence for safety and acceptability of all options, or
      patient preferences. Multiple practice barriers and biases exist that may be
      influencing provider counseling about options for EPF management. CONCLUSION:
      Choosing management for EPF is a preference-sensitive decision. A patient
      centered approach to EPF management should incorporate counseling about all
      treatment options. PRACTICE IMPLICATIONS: Providers can integrate a counseling
      model into EPF management practice that utilizes principles of shared decision
      making and an organized method for eliciting patient preferences, priorities, and
      concerns about treatment options.

PMID- 21093194
TI  - Towards client-centered counseling: development and testing of the WHO Decision
      Making Tool.
AB  - OBJECTIVE: To describe development and testing of a counseling tool intended to
      inform family planning clients while helping the family planning provider
      facilitate the client's decision-making process; and to discuss challenges and
      requisites for shifting to shared decision-making from the extremes of decision
      making dominated by the provider, on one hand, or unaided by the provider, on the
      other. DEVELOPMENT OF THE TOOL: The WHO Decision-Making Tool for Family Planning
      Clients and Providers is derived from evidence-based principles of client
      centered care and counseling. This article discusses how these principles are
      manifested in the Tool and how the Tool aids both provider and client in
      improving counseling. METHODS: Development of the Tool involved formative
      workshops with providers in Indonesia, Mexico, South Africa and Trinidad and
      Tobago and observational evaluation research in Indonesia, Mexico, and Nicaragua.
      Analysis of videotaped counseling sessions quantitatively assessed client
      provider communication and decision-making. Also, focus-group discussions,
      interviews, and a questionnaire collected qualitative data from providers and
      clients. RESULTS: In general, use of the Tool improved providers' counseling
      performance: they engaged clients more and gave more and better tailored
      information. For clients, the Tool increased their communication and involvement.
      Both the Nicaraguan and Mexican studies found marked shifts toward the client in
      the locus of decision-making after introduction of the Tool. PRACTICE
      IMPLICATIONS: Use of the tool improves the performance of both providers and
      clients in family planning counseling and decision-making. There are challenges,
      however, at the levels of both the provider and the organization in sustaining
      these changes and scaling up such initiatives in quality of care.

PMID- 21093196
TI  - Promoting healthy spacing between pregnancies in India: need for differential
      education campaigns.
AB  - OBJECTIVE: Birth spacing intervals are relatively short in India. Healthy spacing
      of 3-5 years between births is an effective way to prevent maternal and child
      mortality and morbidities. Socio-cultural and structural barriers, including
      limited awareness, socio-cultural norms, and misconceptions need to be addressed
      for behavior change. Hence the objective was to understand these barriers and
      accordingly develop separate messages for young women, her husband and her mother
      in-law. METHODS: Data were collected from young women, husbands and mothers-in
      law using qualitative methods. Altogether 16 Focus Group Discussions and 30 in
      depth interviews were conducted. Beliefs related to need of spacing,
      disadvantages of closely spaced pregnancies and messages considered suitable for
      different stakeholders were investigated. Messages were identified for women,
      husband and mother-in-law; communication aids prepared and community workers
      trained to appropriately communicate the messages to stakeholders. Quantitative
      data were collected to measure the effect of the intervention. RESULTS:
      Educational campaign resulted in higher use of contraceptives for spacing among
      registered pregnant women from experimental area compared to control area.
      CONCLUSION: Differential audience specific educational campaign is feasible and
      effective. PRACTICE IMPLICATIONS: For an effective communication in the
      community, workers should know how exactly to convey the different health
      messages to different target population.

PMID- 21093197
TI  - Development, validation, and utilization of a novel antibody specific to the type
      III chicken gonadotropin-releasing hormone receptor.
AB  - Two gonadotropin-releasing hormone receptors (GnRH-Rs) have been characterized in
      chickens to date: cGnRH-R-I and cGnRH-R-III, with cGnRH-R-III being the
      predominant pituitary form. The purpose of the present study was to first
      validate a novel antibody for the specific detection of cGnRH-R-III and second,
      using this antibody, detect changes in cGnRH-R-III protein levels in the
      pituitary gland of male and female chickens during a reproductive cycle. The
      localization of cGnRH-R-III within the anterior pituitary gland was also
      determined. Western blotting of pituitary extracts and transiently transfected
      COS-7 cell lysates revealed that our antibody is highly specific to cGnRH-R-III
      protein. Similarly, when used in immunocytochemistry, this antibody specifically
      detects cells expressing cGnRH-R-III and not cGnRH-R-I. Western blot analyses of
      chicken pituitary gland homogenates show that cGnRH-R-III protein levels are
      significantly greater in sexually mature birds than in immature birds or birds at
      the end of a reproductive cycle (P < 0.0001). A similar pattern was observed for
      both males and females. Additionally, the antibody was able to detect cGnRH-R-III
      in cells along the periphery of the cephalic and caudal lobes of the anterior
      pituitary where the cells containing the gonadotropins are located. In summary,
      we successfully validated a novel antibody to cGnRH-R-III and showed levels of
      cGnRH-R-III protein in the pituitary fluctuate with respect to the reproductive
      status in both male and female chickens.

PMID- 21093195
TI  - Explanatory models of coronary heart disease among South Asian immigrants.
AB  - OBJECTIVE: This study investigated South Asians' explanatory models (EM) of CHD
      and compared them to the biomedical model as part of an effort to inform the
      development of culturally targeted CHD prevention messages. METHODS: We conducted
      in-depth, semi-structured interviews in English, Hindi and Urdu with 75
      respondents from a federally qualified health center and at a community center
      for South Asian immigrants in Chicago, Illinois. RESULTS: While EMs of CHD
      included risk factors from the biomedical model, they also included psychosocial
      and spiritual risk factors. Respondents emphasized that stress causes CHD and
      suggested that CHD was caused by sudden or inexplicable factors. Few respondents
      discussed cholesterol, blood pressure, or diabetes as part of CHD prevention.
      Women and those with lower education had low perceptions of being at-risk for
      CHD. CONCLUSION: South Asians' EMs of CHD encompassed the biomedical model;
      however, EMs also included psychosocial and spiritual factors. PRACTICE
      IMPLICATIONS: Clinicians and health educators should be aware that South Asian
      individual's EM of CHD may include psychosocial and spiritual factors which can
      affect CHD prevention behaviors.

PMID- 21093198
TI  - Concomitance of luteinizing hormone and progesterone oscillations during the
      transition from preluteolysis to luteolysis in cattle.
AB  - The temporal relationships of episodes of luteinizing hormone (LH) oscillations,
      13,14-dihydro-15-keto-PGF2alpha (PGFM) pulses, and progesterone (P4) fluctuations
      during the latter portion of preluteolysis and the early portion of luteolysis
      were characterized. In Experiment 1, the detection of LH episodes in blood
      samples collected every 15 min for 8 h was compared with detection in the samples
      collected every hour in 4 heifers. The number of independently detected
      episodes/heifer (total = 7) was the same for the 15-min and hourly collection
      intervals. In Experiment 2, blood samples were collected every hour (n = 7
      heifers) and retrospectively assigned to 15 h before and 15 h after the
      transitional hour between preluteolysis and luteolysis. During preluteolysis,
      compared with luteolysis, the amplitude of LH oscillations was greater (0.28 +/-
      0.03 vs 0.18 +/- 0.03 ng/mL; P < 0.02) and the interval between peaks of LH
      oscillations was shorter (3.3 +/- 0.3 h vs 4.3 +/- 0.6 h; P < 0.04). The LH peaks
      occurred at the same hour as the peak of a P4 fluctuation in 77% and 29% of LH
      oscillations (P < 0.0009) during preluteolysis and luteolysis, respectively. In
      preluteolysis, synchrony between LH and P4 episodes occurred consistently during
      the P4 rebound after the peak of a PGFM pulse. In luteolysis, the LH peak
      preceded the peak of the P4 rebound. On a temporal basis, the hypothesis was
      supported that episodic LH accounts, at least in part, for the reported P4
      rebound that occurs after the P4 suppression at the peak of a PGFM pulse.

PMID- 21093199
TI  - Lower extremity arteriovenous fistula with central venous stenosis iliocaval
      stenting to treat venous outflow obstruction.
AB  - Maintenance of hemodialysis access for end-stage renal disease continues to be a
      major challenge for vascular surgeons, nephrologists, and primary care
      physicians. This case report highlights the complication and treatment of lower
      extremity central venous stenosis, allowing continued dialysis access for a
      patient with limited remaining fistula options. This stenosis resulted from the
      prolonged use of a lower extremity central venous catheter. This case highlights
      the importance of imaging the central veins in obstruction of lower extremity
      fistulas. Once detected, as in the upper extremity, this can be effectively
      treated using balloon dilation and stenting.

PMID- 21093200
TI  - National trends in utilization and postprocedure outcomes for carotid artery
      revascularization 2005 to 2007.
AB  - OBJECTIVE: This study compared, at a national level, trends in utilization,
      mortality, and stroke after carotid angioplasty and stenting (CAS) and carotid
      endarterectomy (CEA) from 2005 to 2007. METHODS: The Nationwide Inpatient Sample
      (NIS) was queried for patient discharges with International Classification of
      Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes for CAS and CEA.
      The primary outcomes were in-hospital mortality, stroke, hospital charges, and
      discharge disposition. Subgroup analyses were performed to evaluate these
      outcomes by neurologic presentation using chi(2) and multivariable logistic
      regression. RESULTS: Of the 404,256 discharges for carotid revascularization, CAS
      utilization was 66% higher in 2006 than in 2005 (9.3% vs 14%, P = .0004). Crude
      mortality, stroke, and median charges remained higher for CAS than for CEA;
      discharge to home was more common after CEA. Results improved from 2005 to 2007.
      By logistic regression of the total cohort from 2005 to 2006, CAS was
      independently predictive of mortality (odds ratio [OR], 1.47; 95% confidence
      interval [CI], 1.08-2.00; P < .0001). Independent predictors of stroke included
      CAS (OR, 1.43; 95% CI, 1.18-1.73; P < .0001) and symptomatic disease (OR, 2.4;
      95% CI, 2.06-2.93;P < .0001). Among subgroups based on neurological presentation,
      regression showed that CAS significantly increased the odds of stroke in
      asymptomatic patients (OR, 1.6; 95% CI, 1.2-2.0; P = .0003). Among symptomatic
      patients, CAS increased the odds of in-hospital death (OR, 3.0; 95% CI, 1.7-5.1,
      P < .0001) and trended toward significance for stroke (OR, 1.7; 95% CI, 1.0-2.8;
      P = .0569). CONCLUSION: Utilization of CAS has increased from the years 2005 to
      2007 with some improvements in the outcome. Despite improvements in outcome,
      resource utilization remains significantly higher for CAS than CEA.

PMID- 21093201
TI  - The learning curve of robot-assisted laparoscopic aortofemoral bypass grafting
      for aortoiliac occlusive disease.
AB  - BACKGROUND: Since the end of the 20th century, robot-assisted surgery has been
      finding its role among other minimally invasive methods. Vascular surgery seems
      to be another specialty in which the benefits of this technology can be expected.
      Our objective was to assess the learning curve of robot-assisted laparoscopic
      aortofemoral bypass grafting for aortoiliac occlusive disease in a group of 40
      patients. METHODS: Between May 2006 and January 2010, 40 patients (32 men, 8
      women), who were a median age of 58 years (range, 48-75 years), underwent 40
      robot-assisted laparoscopic aortofemoral reconstructions. Learning curve
      estimations were used for anastomosis, clamping, and operative time assessment.
      For conversion rate evaluation, the cumulative summation (CUSUM) technique was
      used. Statistical analysis comparing the first and second half of our group, and
      unilateral-to-bilateral reconstructions were performed. RESULTS: We created 21
      aortofemoral and 19 aortobifemoral bypasses. The median proximal anastomosis time
      was 23 minutes (range, 18-50 minutes), median clamping time was 60 minutes
      (range, 40-95 minutes), and median operative time was 295 minutes (range, 180-475
      minutes). The 30-day mortality rate was 0%, and no graft or wound infection or
      cardiopulmonary or hepatorenal complications were observed. During the median 18
      month follow-up (range, 2-48 months), three early graft occlusions occurred (7%).
      After reoperations, the secondary patency of reconstructions was 100%. Data
      showed a typical short learning curve for robotic proximal anastomosis creation
      with anastomosis and clamping time reduction. The operative time learning curve
      was flat, confirming the procedure's complexity. There were two conversions to
      open surgery. CUSUM analysis confirmed that an acceptable conversion rate set at
      5% was achieved. Comparing the first and second half of our group, all recorded
      times showed statistically significant improvements. Differences between
      unilateral and bilateral reconstructions were not statistically significant.
      CONCLUSIONS: Our results show that the success rate of robot-assisted
      laparoscopic aortofemoral bypass grafting is high and the complication rate is
      low. Anastomosis creation, one of the main difficulties of laparoscopic bypass
      grafting, has been overcome using the robotic operating system and its learning
      curve is short. However, the endoscopic dissection of the aortoiliac segment
      remains the most difficult part of the operation and should be addressed in
      further development of the method to reduce the operative times. Long-term
      results and potential benefits of this minimally invasive method have to be
      verified by randomized controlled clinical trials.

PMID- 21093202
TI  - The impact of adjusting for reliability on hospital quality rankings in vascular
      surgery.
AB  - BACKGROUND: Hospital quality in vascular surgery is often measured using
      mortality. We sought to determine whether adjusting mortality for statistical
      reliability changes hospital quality rankings for vascular surgery. METHODS:
      Patients undergoing five common vascular surgery procedures (open and
      endovascular abdominal aortic aneurysm repair, carotid endarterectomy, lower
      extremity bypass, and aorto-femoral bypass) in the National Surgical Quality
      Improvement Project (NSQIP) in 2007 were identified (n = 14,559). For each
      hospital, we first calculated a ratio of observed to expected mortality (O-E
      ratio) using standard NSQIP techniques. We then adjusted these estimates for
      statistical noise using empirical Bayes methods, a technique known as reliability
      adjustment. We then compared rankings based on the standard O-E ratio to the
      rankings after reliability adjustment. RESULTS: A total of 172 hospitals reported
      an average adjusted mortality rate of 2.4% for the five procedures, varying from
      0% to 17%. After adjusting for statistical noise using reliability adjustment,
      hospital mortality was greatly diminished, varying only from 1.7% to 4.1%. This
      adjustment for reliability had a dramatic effect on hospital rankings. Overall,
      43% of hospitals were reclassified into either a higher or lower quartile of
      performance using traditional methods of risk-adjustment. Fifty-one percent all
      hospitals in the "best" quartile of performance according to traditional O-E
      ratios are not classified in the "best" quartile after adjusting for statistical
      noise. Twenty-six percent of hospitals in the "worst" quartile were no longer
      classified as such after adjusting for noise. CONCLUSIONS: Adjusting mortality
      for reliability reduces statistical noise and provides more stable estimates of
      hospital quality. Reliability adjustment should be standard for comparing
      hospital quality.

PMID- 21093203
TI  - Molecular diagnosis of nonaneurysmal infectious aortitis.
AB  - We report a 79-year-old patient who presented with a fever and abdominal pain.
      The patient was initially thought to have a retroperitoneal fibrosis or
      inflammatory abdominal aortitis in a normal-sized caliber aorta. Broad-range
      polymerase chain reaction (PCR) and DNA sequencing revealed the presence of
      Enterobacter. We finally diagnosed nonaneurysmal infectious aortitis, and we
      performed a successful surgical resection. Establishing a diagnosis of aortic
      infection before formation of an aneurysm is difficult. The molecular diagnostic
      technique was particularly useful in specifying the microbial species and
      diagnosis.

PMID- 21093204
TI  - Morbidity of diaphragmatic surgery for advanced ovarian cancer: retrospective
      study of 148 cases.
AB  - BACKGROUND: Treatment of Advanced Ovarian Cancer (AOC) includes surgery with
      complete cytoreduction, one of the strongest prognostic factors. To achieve
      complete cytoreduction, diaphragmatic surgery is often required. There is
      currently a lack of information in the literature regarding the morbidity and
      impact of this type of surgery. The aim of this study is to report specific
      pulmonary morbidity and overall morbidity associated with diaphragmatic surgery
      in patients with AOC. MATERIALS AND METHODS: We conducted a multicentric (6
      centres), retrospective study that included 148 patients operated on between 2004
      and 2008. Patient characteristics, surgical course and postoperative
      complications were collected. RESULTS: The complete cytoreduction rate was 84%.
      The surgery was categorised by timing as initial, interval or recurrence surgery
      in 38%, 51% and 11% of patients, respectively. In 69% of patients, one or more
      postoperative complications occurred: pulmonary complication (42%), digestive
      fistula (7%) or lymphocyst (18%). The pulmonary complications were pleural
      effusion (37%), pulmonary embolism (5%), pneumothorax (4%) and pulmonary
      infection (2%). These complications required revision surgery, pleural
      evacuation, or lymphocyst evacuation in 13%, 14%, and 11% of the cases,
      respectively. Postoperative mortality was 3%. Risk factors for pulmonary
      complications were the addition of extensive upper surgery to the diaphragmatic
      surgery (p = 0.014) and the size of the diaphragmatic resection (p = 0.012).
      CONCLUSIONS: Diaphragmatic surgery achieved complete removal of the tumour but
      resulted in pulmonary complications in addition to complications of radical
      surgery.

PMID- 21093206
TI  - Prognostic significance of triple negative breast cancer at tumor size 1 cm and
      smaller.
AB  - AIMS: The purpose of this study was to clarify the prognostic significance of
      triple-negative breast cancer (TNBC) with a tumor size <= 1 cm. MATERIALS AND
      METHODS: Patients with primary operable breast cancer with a tumor size <= 1 cm
      were enrolled at Changhua Christian Hospital and National Cheng-Kung University
      Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and
      compared with tumors with any receptor positivity (non-TNBC) for disease-free
      survival (DFS) and cancer-specific survival (CSS). RESULTS: From 1995 to 2006, a
      total of 377 patients with tumor size <= 1 cm were enrolled. Compared with non
      TNBC patients, TNBC patients with a tumor size <= 1 cm as a whole or in a lymph
      node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In
      lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5
      year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative
      subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox
      regression hazard analysis, lymph node invasion was the most important cause of
      disease recurrence and cancer-specific death. CONCLUSION: TNBC is very likely an
      independent risk factor in small (<=1 cm) node-negative invasive breast cancer.
      With tumors 1 cm and smaller, lymph node invasion was the single most important
      prognostic factor.

PMID- 21093205
TI  - Prognostic factors and oncologic outcome in 146 patients with colorectal
      peritoneal carcinomatosis treated with cytoreductive surgery combined with
      hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O.
AB  - AIM: The present study was specifically designed to assess the major clinical and
      pathological variables of patients with colorectal peritoneal carcinomatosis in
      order to investigate whether currently used criteria appropriately select
      candidates for peritonectomy procedures (cytoreductive surgery) combined with
      hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS:
      Preoperative, operative and follow-up data on 146 consecutive patients presenting
      with peritoneal carcinomatosis of colorectal origin and treated by surgical
      cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers
      were prospectively entered in a common database. Univariate and multivariate
      analyses were used to assess the prognostic value of clinical and pathologic
      factors. RESULTS: Over a minimum 24-month follow-up, the overall morbidity rate
      was 27.4% (mortality rate: 2.7%) and was directly related to the extent of
      surgery. Peritoneal cancer index (PCI), unfavorable peritoneal sites, synchronous
      or previously resected liver metastasis and the completeness of cytoreduction,
      all emerged as independent prognostic factors correlated with survival.
      CONCLUSIONS: Until research provides more effective criteria for selecting
      patients based upon the biomolecular features of carcinomatosis, patients should
      be selected according to the existing independent prognostic variables.

PMID- 21093207
TI  - Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary
      thyroid carcinoma: potential markers for aggressive phenotypes.
AB  - BACKGROUND AND OBJECTIVES: Polymorphisms of the VEGF gene are known to affect the
      biological behaviour of cancers but have seldom been studied in thyroid cancer.
      The aim of the current study is to evaluate the prevalence and relevance of VEGF
      A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC).
      MATERIALS AND METHODS: Genomic DNA and total RNA were isolated from paraffin
      embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and
      78 control thyroid tissues. Three DNA polymorphisms (+936C > T, +405C > G and 
      141A > C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were
      studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues
      was studied by real-time PCR. RESULTS: Distribution of polymorphisms in the 5'
      UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all
      significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and
      0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph
      node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were
      more common in PTC of advanced pathological staging (p = 0.018 and 0.017
      respectively). Also, increased expression of VEGF-A mRNA was noted in PTC
      compared to control (p = 0.009). Within the group of patients with conventional
      PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA
      expression than other patients (p = 0.0003). CONCLUSION: These findings suggest
      that VEGF polymorphisms and mRNA expression may predict the aggressiveness
      behaviour of thyroid cancer.

PMID- 21093208
TI  - ?

PMID- 21093209
TI  - [Erythema nodosum and Hodgkin's disease: a rare association that should not be
      neglected].

PMID- 21093210
TI  - [Beta-blockers in portal hypertension: Unexpected limitations!].

PMID- 21093211
TI  - Comparison of simultaneous bilateral and staged bilateral total knee arthroplasty
      in terms of perioperative complications.

PMID- 21093213
TI  - Usefulness of short-term data for evaluating cataract surgery outcomes.

PMID- 21093214
TI  - Psoriatic intraepithelial keratitis after laser in situ keratomileusis treatment.
AB  - A 36-year-old woman with chronic psoriasis developed blurring of vision and
      intraepithelial infiltrates within the flap in the left eye concurrent with the
      appearance of acute psoriatic generalized skin lesions 14 days after bilateral
      laser in situ keratomileusis. After treatment with topical antibiotic and steroid
      agents and topical artificial tears, the intraepithelial infiltrates within the
      flap completely resolved. The final uncorrected distance visual acuity was 1.0 in
      both eyes, along with complete resolution of the dermatologic psoriatic lesions.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 21093215
TI  - Evaluation of trypan-blue and indocyanine-green staining of iris prostheses.

PMID- 21093216
TI  - An object location detector enabling people with developmental disabilities to
      control environmental stimulation through simple occupational activities with
      battery-free wireless mice.
AB  - This study assessed whether two persons with developmental disabilities would be
      able to actively perform simple occupational activities by controlling their
      favorite environmental stimulation using battery-free wireless mice with a newly
      developed object location detection program (OLDP, i.e., a new software program
      turning a battery-free wireless mouse into an object location detector). This
      study was performed according to an ABAB design, in which A represented the
      baseline and B represented intervention phases. Data showed that both
      participants significantly increased their target response (performing simple
      occupational activities) to activate the control system to produce environmental
      stimulation during the intervention phases. Practical and developmental
      implications of the findings are discussed.

PMID- 21093217
TI  - The impact of prolonged rotary ventricular assist device support upon ventricular
      geometry and flow kinetics.
AB  - BACKGROUND: The aim of this study was to determine the impact of prolonged left
      ventricular assist device (VAD) support on cardiac ventricular geometry and VAD
      flow kinetics. METHODS: Nineteen patients with end-stage heart failure underwent
      the implantation of HeartMate II rotary flow VADs. Left and right ventricular
      geometry and VAD flow kinetics were assessed by transthoracic echocardiography
      early (7 +/- 1 days) and late (113 +/- 21 days) after VAD implantation. RESULTS:
      Left ventricular end-diastolic internal dimension decreased by 21% and 35%,
      respectively, early and late after VAD implantation (n = 19; P < .001 vs before
      VAD implantation). Right ventricular end-diastolic internal dimension did not
      decrease at either time. Hemodynamic trends were similar. VAD inflow obstruction
      by myocardium was observed in eight patients, seven of whom demonstrated
      significantly increased variation of VAD inflow during the cardiac cycle
      ("pulsatility") detected by Doppler studies. Medical or surgical intervention
      returned VAD flow patterns toward baseline in seven of eight patients with VAD
      obstructions. CONCLUSIONS: Prolonged rotary VAD support unloads the left
      ventricle, with modest effects on the right ventricle. These changes are often
      associated with alterations of VAD flow kinetics, requiring therapeutic
      intervention. These findings indicate the usefulness of echocardiographic
      surveillance in patients undergoing prolonged VAD support.

PMID- 21093218
TI  - Heart rate dynamics in temporal lobe epilepsy-A long-term follow-up study.
AB  - The aim of the present study was to prospectively evaluate long-term changes in
      interictal heart rate variability (HRV) in patients with temporal lobe epilepsy
      (TLE). A 24-h ECG was recorded at baseline and after a mean follow-up of 6.1
      years in 18 patients with refractory TLE and 18 patients with well-controlled
      TLE. After the follow-up, the Poincare components SD(1) (p=0.039) and SD(2)
      (p=0.001) were decreased in patients with refractory TLE compared to baseline,
      whereas in patients with well-controlled TLE no changes (p>0.05) in HR
      variability were observed. The reduction in HRV seems to be progressive in
      patients with chronic refractory TLE with recurrent seizures.

PMID- 21093219
TI  - Increased Framingham 10-year risk of coronary heart disease in middle-aged and
      older patients with psychotic symptoms.
AB  - OBJECTIVE: The Framingham 10-risk of coronary heart disease (CHD) has been a
      widely studied estimate of cardiovascular risk in the general population.
      However, few studies have compared the relative risk of developing CHD in
      antipsychotic-treated patients with different psychiatric disorders, especially
      in older patients with psychotic symptoms. In this study, we compared the 10-year
      risk of developing CHD among middle-aged and older patients with psychotic
      symptoms to that in the general population. METHOD: We analyzed baseline data
      from a study examining metabolic and cardiovascular effects of atypical
      antipsychotics in patients over age 40 with psychotic symptoms. After excluding
      patients with prior history of CHD and stroke, 179 subjects were included in this
      study. Among them, 68 had a diagnosis of schizophrenia, 42 mood disorder, 38
      dementia, and 31 PTSD. Clinical evaluations included medical and pharmacologic
      treatment history, physical examination, and clinical labs for metabolic
      profiles. Using the Framingham 10-year risk of developing CHD based on the
      Framingham Heart Study (FHS), we calculated the risk CHD risk for each patient,
      and then compared relative risk in each psychiatric diagnosis to the risks
      reported in the FHS. RESULTS: The mean age of entire sample was 63 (range 40-94)
      years, 68% were men. The Framingham 10-year risk of CHD was increased by 79% in
      schizophrenia, 72% in PTSD, 61% in mood disorder with psychosis, and 11% in
      dementia relative to the risk in general population from the FHS. CONCLUSIONS: In
      this sample of middle-aged and older patients with psychotic symptoms, we found a
      significantly increased 10-year risk of CHD relative to the estimated risk from
      FHS, with the greatest increased risk for patients with schizophrenia and PTSD.
      Development of optimally tailored prevention and intervention efforts to decrease
      different risk components in these patients could be an important step to help
      decrease the risks of CHD and overall mortality in this vulnerable population.

PMID- 21093220
TI  - Trajectories of the course of schizophrenia: from progressive deterioration to
      amelioration over three decades.
AB  - BACKGROUND: The extent of heterogeneity in the long-term course of schizophrenia
      is unclear. AIMS: To examine the course of schizophrenia in a population-based
      cohort. METHODS: This study included all Israeli individuals born in 1970-1988,
      of North African or European origin (N=2290), entered in the National Psychiatric
      Hospitalization Case Registry with a last discharge diagnosis of schizophrenia
      (1978-2004) and followed to 2009. Linked socio-demographic information was
      extracted from the Population Registry. Based on the number of hospitalized days
      at each age, trajectory groups were empirically derived, plotted and compared on
      psychiatric hospitalization measures of the course of illness, social factors and
      family stressors. RESULTS: Trajectory analysis identified four course groups.
      Group I (57%) assumed a prototypical course, had an average first hospitalization
      age of 20, deteriorated until 23 and then ameliorated. Group II (15.5%) assumed
      an early-onset protracted course, had an average first hospitalization age of
      17.1, and deteriorated until 21. Group III (15%) assumed a late-onset with
      longest deterioration period course, had an average first hospitalization age of
      22.7, and deteriorated until 29. Group IV (12%) assumed an early-onset refractory
      illness course, had an average first hospitalization age of 18, and had the
      longest hospitalization period. Groups significantly differed on hospitalization
      (i.e., onset), social (i.e., socioeconomic and ethnic status) and familial
      factors (i.e., parental death). Despite group differences all deteriorated and
      then ameliorated on average by the age of 23. CONCLUSIONS: The course of
      schizophrenia was heterogeneous, yet evolved from deterioration to assume a
      course consistent with amelioration.

PMID- 21093221
TI  - Autosomal recessive congenital ichthyosis maps to chromosome 15q26.3 in an
      isolated aboriginal population from southern Taiwan.

PMID- 21093222
TI  - Two new variants of and creation of a repository for Stenotrophomonas maltophilia
      quinolone protection protein (Smqnr) genes.

PMID- 21093223
TI  - Effects of season of birth and a common MTHFR gene variant on the risk of
      schizophrenia.
AB  - Season of birth - in particular winter birth - has been persistently related to
      increased schizophrenia risk. Variation in folate intake is among the
      explanations for this seasonal effect. Methylenetetrahydrofolate reductase
      (MTHFR) is an essential enzyme in the folate mediated methylation transfer
      reactions. Interestingly, the MTHFR gene has been related to schizophrenia risk
      in various studies. We investigated a possible interaction between MTHFR 677C>T
      polymorphism and winter birth in the development of schizophrenia in a group of
      742 schizophrenia patients and 884 control subjects. All subjects were of Dutch
      ancestry. Winter birth (December up to and including February) was associated
      with a 20% increase in schizophrenia risk (odds ratio (OR) of 1.20 and 95%
      confidence interval (CI), 0.96-1.5; P=0.113). The MTHFR 677TT genotype was
      associated with an overall schizophrenia risk of 1.13 (95% CI, 0.82-1.57;
      P=0.454) compared with the MTHFR 677CC genotype. In the winter period the MTHFR
      677TT genotype associated schizophrenia risk was 0.90 (95% CI, 0.47-1.70;
      P=0.744). In conclusion, neither winter birth nor MTHFR genotype were
      significantly associated with increased schizophrenia risk. There was no evidence
      for interaction between MTHFR 677TT genotype and winter birth in the development
      of schizophrenia.

PMID- 21093224
TI  - Cerebral metabolic responses to 5-HT2A/C receptor activation in mice with
      genetically modified serotonin transporter (SERT) expression.
AB  - Variation in the human serotonin transporter gene (hSERT; 5-HTT) resulting in a
      life-long alteration in SERT function influences anxiety and the risk of
      developing affective disorders. The mechanisms underlying the influence of the
      hSERT gene on these phenotypes remain unclear but may involve altered 5-HT
      receptor function. Here we characterise the cerebral metabolic response to 5
      HT(2A/C) receptor activation in two transgenic mouse models of altered SERT
      function, SERT knock-out (SERT KO) and hSERT over-expressing (hSERT OE) mice, to
      test the hypothesis that genetically mediated variability in SERT expression
      alters 5-HT(2A/C) function. We found that a constitutive increase in SERT
      expression (hSERT OE) enhanced, whereas a constitutive decrease in SERT
      expression (SERT KO) attenuated, 5-HT(2A/C) function. Therefore, altered 5
      HT(2A/C) receptor functioning in response to hSERT gene variation may contribute
      to its influence on affective phenotypes.

PMID- 21093225
TI  - Inhibition of protein adsorption and cell adhesion on PNIPAAm-grafted
      polyurethane surface: effect of graft molecular weight.
AB  - In this work, the effect of molecular weight (MW) of surface grafted poly(N
      isopropylacrylamide) (PNIPAAm) on protein adsorption and cell adhesion was
      investigated systematically. PNIPAAm-grafted polyurethane (PU) surfaces of
      varying graft MW were prepared via conventional radical polymerization. The MW
      was controlled by adjusting the monomer concentration. Fibrinogen (Fg) and human
      serum albumin (HSA) were selected as model proteins and their adsorption from
      phosphate-buffered saline (PBS, pH 7.4) and blood plasma at 37 degrees C was
      measured using a radiolabeling method and immunoblot analysis respectively. It
      was found that in both media, as the MW increased, the adsorption of these two
      proteins decreased gradually reaching a plateau value at MW above 7.9*10(4).
      Compared to the unmodified PU, the surface grafted with PNIPAAm of MW 14.6*10(4)
      reduced the adsorption of Fg and HSA in PBS by 91% and 86%, respectively.
      Moreover, the surfaces with higher MW PNIPAAm showed minimal adhesion of L929
      cells presumably due to the absence of cell-adhesive proteins on the surfaces.

PMID- 21093226
TI  - Solidified liquid layer model makes quartz crystal microbalance a convenient
      molecular ruler.
AB  - The applications of quartz crystal microbalance (QCM) in biointerfaces are
      limited by its quantitative ambiguities caused by viscoelasticity and solution
      effects. Although many studies clearly indicated that the quantitative
      interpretation of QCM data needed caution, none of those studies provided a
      practical solution that enabled general and quantitative interpretation of QCM
      data. Recently we proposed a "solidified liquid layer" model that enabled QCM to
      be used as a biomolecular ruler. Here we applied five kinds of proteins with
      significant differences in their sizes and shapes to further validate this model.
      The effective thickness (T(eff)) of surface immobilized, hydrated proteins were
      10.2, 4.7, 1.8 and 4.8 nm for rabbit IgG, streptavidin, lysozyme, and bovine
      serum albumin, respectively. The critical number of stakes needed for the
      formation of a solidified liquid layer was found to be protein dependent. We
      believed this "solidified liquid layer" model will facilitate the popularization
      of QCM as a valuable tool in biointerface studies, such as protein adsorption
      process or the conformational change on surface.

PMID- 21093227
TI  - Direct energy transfer from conjugated polymer to DNA intercalated dye: label
      free fluorescent DNA detection.
AB  - The development of methods for DNA detection is of importance in disease
      diagnosis, gene-targeted drug discovery and molecular biology field. In this
      paper, we synthesize a new cationic water-soluble CP containing fluorene moiety
      and flexible ethylenic moiety in the backbone (PFV) for label-free DNA detection.
      The conformational freedom of PFV provides stronger interactions with double
      stranded DNA (dsDNA) and optimizes the orientation of transition moments between
      PFV and ethidium bromide (EB) intercalated in dsDNA. The efficient FRET from PFV
      (donor) to EB (acceptor) intercalated in dsDNA is observed and the emission of EB
      is amplified by the good light-harvesting ability of conjugated polymers. The
      interactions between PFV and DNA can also be probed by measuring the FRET ratio
      between PFV and EB intercalated in DNA. In comparison to other DNA detection
      assays based on FRET and conjugated polymers, synthesis of dye-labeled DNA probe
      is avoided in our method, which significantly reduces the cost and the synthetic
      complexity. The PFV/dsDNA/EB system provides promising applications on DNA
      detection with a simply, fast and label-free manner.

PMID- 21093228
TI  - Interobserver variability in clinical target volume delineation in tangential
      breast irradiation: a comparison between radiation oncologists and radiation
      therapists.
AB  - AIMS: The delineation of target volumes has been radiation oncologist led. If
      radiation therapists were to undertake this task, work processes may be more
      efficient and the skills set of radiation therapy staff broadened. This study was
      undertaken to quantify interobserver variability of breast target volumes between
      radiation oncologists and radiation therapists. MATERIALS AND METHODS: The
      planning computed tomography datasets of 30 patients undergoing tangential breast
      radiotherapy were utilised. Four radiation oncologists and four radiation
      therapists independently contoured the clinical target volume (CTV) of the breast
      on planning computed tomography using a written protocol. The mean CTV volumes
      and the mean distance between centres of volume (COV) were determined for both
      groups to determine intergroup variation. Each of the radiation oncologists'
      readings in turn has been used as the gold standard and compared with that of the
      radiation therapists. The concordance index for each patient's CTV was determined
      relative to the gold standard for each group. A paired t-test was used for
      statistical comparison between the groups. An intraclass correlation coefficient
      was calculated to measure the agreement between the radiation oncologist and
      radiation therapist groups. RESULTS: The mean concordance index was 0.81 for
      radiation oncologists and 0.84 for radiation therapists. The intraclass
      correlation coefficient for the mean volume was 0.995 (95% confidence interval
      0.981-0.998) between radiation oncologist- and radiation therapist-contoured
      volumes. The intraclass correlation for the mean difference between radiation
      oncologists' and radiation therapists' COV was 0.999 (95% confidence interval
      0.999-1.000). CONCLUSIONS: Interobserver variability between radiation
      oncologists and radiation therapists was found to be low. Radiation therapists
      could potentially assume the role of CTV voluming for breast radiotherapy
      provided a standardised contouring protocol is in place.

PMID- 21093230
TI  - The association of adiponectin and low-grade inflammation with the course of
      metabolic syndrome.
AB  - BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with low-grade
      inflammation. The connections of adiponectin and inflammatory cytokines with the
      course of MetS are not well-known. The aim of this study was to investigate the
      relation of adiponectin and low-grade inflammation with the development or
      resolution of MetS. METHODS AND RESULTS: In the town of Pieksamaki, Finland, five
      complete age groups (n = 1.294) were invited for health check-ups in 1997-1998
      for the first time and in 2003-2004 for the second time. The final study
      population included 284 men and 396 women. MetS was defined according to the
      National Cholesterol Education Program criteria in the beginning and at the end
      of the 6-year research period, and adiponectin, high-sensitivity C-reactive
      protein (hs-CRP), interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1
      beta (IL-1beta) levels were determined from baseline samples. Both male and
      female study subjects were divided into four groups according to the diagnosis of
      MetS in the two check-ups: not diagnosed at either check-up (No MetS), diagnosed
      only at the second check-up (Incident MetS), diagnosed only at the first check-up
      (Resolute MetS), and diagnosed at both check-ups (Persistent MetS). Baseline
      adiponectin, IL-1Ra and IL-1beta levels and IL-1beta/IL-1Ra -ratio were found to
      predict Incident MetS, when adjusted for the change in BMI, age, smoking status
      and physical activity. Our data also suggested that a high adiponectin level and
      low hs-CRP and IL-1Ra levels predict the resolution of MetS. CONCLUSION:
      Adiponectin and inflammatory markers can predict the course of MetS.

PMID- 21093231
TI  - Body mass interacts with fat quality to determine the postprandial lipoprotein
      response in healthy young adults.
AB  - BACKGROUND AND AIMS: Postprandial lipemia predicts the evolution of
      cardiovascular disease. Obesity is associated with an increase in the magnitude
      of postprandial lipemia. Our objective was to evaluate the influence of body mass
      index (BMI) on the effects of acute ingestion of different types of fat on the
      postprandial lipemic response. METHODS AND RESULTS: Twenty-one healthy men
      followed a 4-week baseline diet and then consumed three fat-loaded meals that
      included 1g fat/kg body wt (65%fat) according to a randomized crossover design.
      The compositions of the three meals were olive oil meal (22% saturated fatty
      acids (SFA), 38% monounsaturated fatty acids (MUFA), 4% polyunsaturated fatty
      acids (PUFA)); butter meal (35% SFA, 22% MUFA, 4% PUFA); walnuts meal (20% SFA,
      24% MUFA, 16% PUFA, and 4% alpha-linolenic acid). Higher-weight (HW) subjects
      (BMI greater than the median 26.18 kg/m(2), n = 11) presented higher incremental
      area under the curve (iAUC) for triglycerides (TG), both in large- and small-TG
      rich lipoproteins (TRL) than lower-weight (LW) subjects (BMI<26.18 kg/m(2), n =
      10) (p<0.05), and a similar trend for plasma TG (p = 0.084). Moreover, HW
      subjects presented higher concentrations for small TRL-cholesterol and small TRL
      TG in different timepoints of the postprandial lipemia after the intake of
      enriched walnuts or butter meals compared with the olive oil-enriched meal (p <
      0.05) No significant differences were observed between the three types of meals
      in the postprandial response of LW subjects. CONCLUSION: HW subjects present a
      greater postprandial response than LW subjects, and they benefit from the
      consumption of monounsaturated fatty acids from olive oil, to lower their levels
      of TRL particles during the postprandial state.

PMID- 21093229
TI  - Typical breakfast food consumption and risk factors for cardiovascular disease in
      a large sample of Italian adults.
AB  - BACKGROUND AND AIMS: The overall consumption of foods most frequently consumed in
      a typical Italian breakfast might be associated with a better cardiovascular risk
      profile in Italian adults. METHOD SAND RESULTS: 18,177 subjects (53,2% women),
      aged >= 35 yrs, randomly selected from the Moli-sani Project population were
      studied. The European Prospective Investigation into Cancer and Nutrition (EPIC)
      FFQ was used for dietary assessment. To derive breakfast pattern, an "a priori"
      approach was used: firstly, foods typical of the Italian breakfast were selected:
      milk, coffee, tea, yogurt, crispbread/rusks, breakfast cereals, brioche,
      biscuits, honey, sugar and jam. The breakfast score was obtained adding the
      amounts of all selected foods, expressed in grams/day, previously standardized to
      mean zero and standard deviation 1. Subjects showing a higher breakfast score
      appeared to be younger, more frequently women or smokers, with higher social
      status but less likely practicing physical activity. After multivariable
      analyses, subjects with a higher breakfast food consumption had a lower risk to
      have high body mass index, abdominal obesity, systolic and diastolic blood
      pressure, blood glucose, triglycerides, total cholesterol (P < 0.0001 for all)
      and C Reactive Protein (P = 0.022). The associations were unrelated to age, sex,
      smoking, obesity, physical activity and social status. Subjects with a higher
      food breakfast score also showed a better physical healthy status score, a lower
      risk of metabolic syndrome (OR = 0.63; 0.55-0.72 95% CI) and of future CVD (P <
      0.0001 for both women and men). CONCLUSION: Consumption of typical Italian
      breakfast foods positively affects CVD risk profile in an adult Italian
      population.

PMID- 21093232
TI  - Plasminogen activator inhibitor 1 and visceral obesity during pronounced weight
      loss after bariatric surgery.
AB  - BACKGROUND AND AIMS: Elevated plasminogen activator inhibitor 1 (PAI-1)
      concentrations are a hallmark of obesity and are considered to contribute to the
      development of cardiovascular disease. As adipose tissue constitutes a major
      source for PAI-1 in obesity, we investigated the individual contribution of
      subcutaneous and intra-abdominal fat on PAI-1 concentrations during pronounced
      weight loss after bariatric surgery. METHODS AND RESULTS: Thirty-seven obese
      adults were examined before and 18 months after surgery. Abdominal fat
      distribution was determined by ultrasound, metabolic parameters and plasma PAI-1
      levels by standard methods. BMI was reduced by 9.2 +/- 4.9 kg/m(2), while total
      fat mass and visceral fat diameter (VFD) decreased by 20.7 +/- 11.9 kg and 4.2 +/
      2.3 cm, respectively. Concomitantly, PAI-1 levels diminished by 3.2 +/- 5.6
      ng/ml (all p <= 0.015). Change in PAI-1 levels was correlated with change in VFD
      (r = 0.441, p = 0.008), but not with subcutaneous fat diameter. In stepwise
      multiple regression analysis change in VFD was an independent predictor of change
      in PAI-1 concentrations. When adjusted for age and sex or total fat mass
      associations between PAI-1 and VFD remained significant. CONCLUSION: We
      demonstrate that VFD is a major determinant for PAI-1 concentrations during
      pronounced weight loss after bariatric surgery. Thus, significant reduction of
      visceral fat mass may contribute to the reduced cardiovascular morbidity and
      mortality after bariatric surgery by a concomitant decrease in PAI-1
      concentrations.

PMID- 21093233
TI  - Plasma lipid fatty acid composition, desaturase activities and insulin
      sensitivity in Amerindian women.
AB  - BACKGROUND AND AIMS: Two Amerindian populations--Shuar women living in the
      Amazonian rain forest under traditional conditions and urbanized women in a
      suburb of Lima were studied. The fatty acid composition in plasma lipids and the
      relationships between fatty acid composition and metabolic variables were
      studied, as well as in a reference group of Swedish women. METHODS AND RESULTS:
      Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid
      composition. Women in Lima had more body fat, higher fasting insulin and leptin
      and lower insulin sensitivity than the Shuar women, who had insulin sensitivity
      similar to Swedish women. Shuar women had very high proportions (mean; SD) of
      palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl
      esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low
      fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase
      was about twice as high in the Shuar compared with Lima women, suggesting neo
      lipogenesis, while the delta 5 desaturase activity did not differ. The Lima
      women, as well as the Swedish, showed strong positive correlations between SCD-1
      activity on the one hand and fasting insulin and HOMA index on the other. These
      associations were absent in the Shuar women. CONCLUSIONS: The high SCD-1 activity
      in the Shuar women may reflect increased lipogenesis in adipose tissue. It also
      illustrates how a low fat diet rich in non-refined carbohydrates can be linked to
      a good metabolic situation.

PMID- 21093234
TI  - Cytotoxicity effects of amiodarone on cultured cells.
AB  - Amiodarone is a potent anti-arrhythmic drug used for the treatment of cardiac
      arrhythmias. Although, the effects of amiodarone are well characterized on post
      ischemic heart and cardiomyocytes, its toxicity on extra-cardiac tissues is still
      poorly understood. To this aim, we have monitored the cytotoxicity effects of
      this drug on three cultured cell lines including hepatocytes (HepG2), epithelial
      cells (EAhy 926) and renal cells (Vero). We have investigated the effects of
      amiodarone on (i) cell viabilities, (ii) heat shock protein expressions (Hsp 70)
      as a parameter of protective and adaptive response and (iii) oxidative damage.Our
      results clearly showed that amiodarone inhibits cell proliferation, induces an
      over-expression of Hsp 70 and generates significant amount of reactive oxygen
      species as measured by lipid peroxidation occurrence. However, toxicity of
      amiodarone was significantly higher in renal and epithelial cells than in
      hepatocytes. Vitamin E supplement restores the major part of cell mortalities
      induced by amiodarone showing that oxidative damage is the predominant toxic
      effect of the drug.Except its toxicity for the cardiac system, our findings
      demonstrated that amiodarone can target other tissues. Therefore, kidneys present
      a high sensibility to this drug which may limit its use with subjects suffering
      from renal disorders.

PMID- 21093235
TI  - ESCOP's role in defining a scientific foundation for herbal medicinal products.

PMID- 21093236
TI  - Effect of storage temperature and length on fatty acid composition of fingertip
      blood collected on filter paper.
AB  - We have compared the fatty acids of the capillary and venous whole blood samples
      collected on the commercially developed blood collection paper and standard grade
      filter paper extracted by either the direct methylation or conventional method
      (including various blood lipids fractions). Also, reproducibility of fatty acids
      extracted from dried blood on the filter paper after storing at room temperature
      up to 2 months and at 4 degrees C up to 6 months was assessed. In conclusion, the
      direct methylation of fingertip blood collected on both brand of papers produced
      fatty acids that reflected venous blood fatty acids extracted by the conventional
      method. Of the eight fatty acids evaluated, capillary DHA showed the strongest
      correlation with DHA of the venous whole lipids as well as various lipid
      fractions of the plasma and red cells. However, a prolonged storage of blood
      samples at 4 degrees C had deleterious effect on the qualitative value of fatty
      acids, especially DHA.

PMID- 21093237
TI  - Autoimmunity.

PMID- 21093238
TI  - Allergen-specific pattern recognition receptor pathways.
AB  - Allergic diseases continue to plague modernized societies, underscoring the need
      to identify the molecular basis for the propensity of a small number of
      environmental proteins to provoke maladaptive, allergic responses. Recent data
      suggest that the ability of allergenic proteins to drive allergic responses in
      susceptible hosts is driven by their unique innate immune activating
      capabilities. Although the identification of allergen-specific pattern
      recognition receptors is in its infancy, studies to date have shown that
      allergens drive Th2-biased immune responses via directly engaging C-type lectin
      receptors (dectin-2, DC-SIGN, and mannose receptor) on dendritic cells and/or
      mimicking toll-like receptor 4 signaling complex molecules expressed on airway
      structural cells. Elucidation of the specific innate immune pathways activated by
      allergens holds great promise in defining new therapeutic targets for the
      treatment of allergic diseases.

PMID- 21093239
TI  - Why should mesenchymal stem cells (MSCs) cure autoimmune diseases?
AB  - The adult stem/progenitor cells from bone marrow and other tissues referred to as
      mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) display a
      significant therapeutic plasticity as reflected by their ability to enhance
      tissue repair and influence the immune response both in vitro and in vivo. In
      this review we will focus on the paradigmatic preclinical experience achieved
      testing MSCs in experimental autoimmune encephalomyelitis (EAE), a model for
      multiple sclerosis. We will emphasize how the paradigm changed over time from the
      original prediction that MSCs would enhance tissue repair through their
      transdifferentiation into somatic cells to the current paradigm that they can
      produce therapeutic benefits without engraftment into the injured tissues. The
      data will be reviewed in terms of the potentials of MSCs for therapy of
      autoimmune diseases.

PMID- 21093240
TI  - Optimizing the utility of high-resolution computed tomography in diagnosing
      cryptogenic organizing pneumonia.

PMID- 21093241
TI  - Impact on clinical decision making of quality control standards applied to sputum
      analysis in COPD.
AB  - PURPOSE: Sputum analysis is important in COPD exacerbation management. We
      determined whether application of stringent quality control criteria for sputum
      samples had an impact on culture results. METHODS: We analyzed sputum samples of
      108 patients during stable COPD and during exacerbations. To all samples quality
      control standards and culture interpretation rules according to the American
      Society of Microbiologists (ASM) were applied. RESULTS: In sputum exacerbation
      samples considered appropriate according to ASM quality standards, criteria for
      infection (40%) were met more often compared to inappropriate samples (13%) (p <
      0.001). The same pattern was observed when applying these rules to sputum samples
      obtained during stable disease, (50% vs. 18%, p < 0.001). There was no difference
      in the percentage of infectious cultures obtained during the stable state and
      exacerbations. CONCLUSIONS: Applying stringent quality control criteria to sputum
      samples can have a profound effect on the labeling of sputum samples as
      infectious, and therefore on clinical decision making.

PMID- 21093242
TI  - The cell biology of the germ cell life cycle.

PMID- 21093243
TI  - Endoplasmic reticulum stress-sensing mechanisms in yeast and mammalian cells.
AB  - Upon endoplasmic reticulum (ER) stress, ER-located transmembrane stress sensors
      evoke diverse protective responses. Although ER stress-dependent activation of
      the sensor proteins is partly explained through their negative regulation by the
      ER-located chaperone BiP under non-stress conditions, each of the sensors is also
      regulated by distinct mechanism(s). For instance, yeast Ire1 is fully activated
      via its direct interaction with unfolded proteins accumulated in the ER. This
      insight is consistent with a classical notion that unfolded proteins per se
      trigger ER-stress responses, while various stress stimuli also seem to activate
      individual sensors independently of unfolded proteins and in a stimuli-specific
      manner. These properties may account for the different responses observed under
      different conditions in mammalian cells, which carry multiple ER-stress sensors.

PMID- 21093245
TI  - I-BAR domain proteins: linking actin and plasma membrane dynamics.
AB  - Dynamic plasma membrane rearrangements occur during many cellular processes
      including endocytosis, morphogenesis, and migration. Actin polymerization
      together with proteins that directly deform membranes, such as the BAR
      superfamily proteins, is essential for generation of membrane invaginations
      during endocytosis. Importantly, recent studies revealed that direct membrane
      deformation contributes also to the formation of plasma membrane protrusions such
      as filopodia and lamellipodia. Inverse BAR (I-BAR) domain proteins bind
      phosphoinositide-rich membrane with high affinity and generate negative membrane
      curvature to induce plasma membrane protrusions. I-BAR domain proteins, such as
      IRSp53, MIM, ABBA, and IRTKS also harbor many protein-protein interaction modules
      that link them to actin dynamics. Thus, I-BAR domain proteins may connect direct
      membrane deformation to actin polymerization in cell morphogenesis and migration.

PMID- 21093244
TI  - New mechanisms and functions of actin nucleation.
AB  - In cells the de novo nucleation of actin filaments from monomers requires actin
      nucleating proteins. These fall into three main families--the Arp2/3 complex and
      its nucleation promoting factors (NPFs), formins, and tandem-monomer-binding
      nucleators. In this review, we highlight recent advances in understanding the
      molecular mechanism of actin nucleation by both well-characterized and newly
      identified nucleators, and explore current insights into their cellular functions
      in membrane trafficking, cell migration and division. The mechanisms and
      functions of actin nucleators are proving to be more complex than previously
      considered, with extensive cooperation and overlap in their cellular roles.

PMID- 21093246
TI  - An evaluation on the environmental consequences of residual CFCs from obsolete
      household refrigerators in China.
AB  - Chlorofluorocarbons (CFCs) contained in household refrigerators consist mainly of
      CFC-11 and CFC-12, which will be eventually released into the environment.
      Consequentially, environmental releases of these refrigerants will lead to ozone
      depletion and contribute significantly to the greenhouse effect, if waste
      refrigerators are not disposed of properly. In the present paper, the potential
      release of residual CFCs and their substitutes from obsolete household
      refrigerators in China is examined, and their contributions to ozone depletion
      and greenhouse effect are compared with those of other recognized ozone-depleting
      substances (ODS) and greenhouse gases (GHGs). The results imply that annual
      potential amounts of released residual CFC-11 and CFC-12 will reach their
      maximums at 4600 and 2300 tons, respectively in 2011, and then decrease gradually
      to zero until 2020. Meanwhile, the amounts of their most widely used substitutes
      HCFC-141b and HFC-134a will keep increasing. Subsequently, the contribution ratio
      of these CFCs and their substitutes to ozone depletion will remain at 25% through
      2011, and reach its peak value of 34% by 2018. The contribution to greenhouse
      effect will reach its peak value of 0.57% by 2010. Moreover, the contribution
      ratio of these CFCs to the total global release of CFCs will steadily increase,
      reaching its peak of 15% by 2018. Thus, this period from 2010 to 2018 is a
      crucial time during which residual CFCs and their substitutes from obsolete
      household refrigerators in China will contribute significantly to ozone
      depletion.

PMID- 21093247
TI  - Enlarged gold-tipped silicon microprobe arrays and signal compensation for multi
      site electroretinogram recordings in the isolated carp retina.
AB  - In order to record multi-site electroretinogram (ERG) responses in isolated carp
      retinae, we utilized three-dimensional (3D), extracellular, 3.5-MUm-diameter
      silicon (Si) probe arrays fabricated by the selective vapor-liquid-solid (VLS)
      growth method. Neural recordings with the Si microprobe exhibit low signal-to
      noise (S/N) ratios of recorded responses due to the high-electrical-impedance
      characteristics of the small recording area at the probe tip. To increase the S/N
      ratio, we designed and fabricated enlarged gold (Au) tipped Si microprobes (10
      MUm-diameter Au tip and 3.5-MUm-diameter probe body). In addition, we
      demonstrated that the signal attenuation and phase delay of ERG responses
      recorded via the Si probe can be compensated by the inverse filtering method. We
      conclude that the reduction of probe impedance and the compensation of recorded
      signals are useful approaches to obtain distortion-free recording of neural
      signals with high-impedance microelectrodes.

PMID- 21093248
TI  - Biomimetic sensing layer based on electrospun conductive polymer webs.
AB  - The aim of the present study is to combine a bio-inspired nanofibrous artificial
      epithelium to the electronic nose (e-nose) principles. The sensing device set up
      was an electronic nose consisting of an array of 9 micro-chemoresistors (Cr-Au,
      3*3) coated with electrospun nanofibrous structures. These were comprised of
      doped polyemeraldine base blended with 3 different polymers: polyethylene oxide,
      polyvinilpyrrolidone and polystyrene, which acted as carriers for the conducting
      polymer and were the major responsible of the features of each fibrous overlay
      (electrical parameters, selectivity and sensitivity ranges). The two sensing
      strategies here adopted and compared consisted in the use of 2 different textural
      coatings: a single- and a double-overlay, where the double-overlay resulting from
      overdeposition of 2 different polymer blends. Such e-nose included a plurality of
      nanofibres whose electrical parameters were at the same time depending on each
      polymer exposure to analytes (NO(2), NH(3)) and on the spatial distribution of
      the interlacing fibres. The morphology of the coating arrangements of this novel
      e-nose was investigated by scanning electron microscopy (SEM) and its sensor
      responses were processed by multicomponent data analyses (PCA and PLS) reporting
      encouraging results for detection and recognition of analytes at ppb levels.

PMID- 21093249
TI  - Development of surface plasmon resonance imaging for detection of Acidovorax
      avenae subsp. citrulli (Aac) using specific monoclonal antibody.
AB  - An immunosensor based on surface plasmon resonance imaging (SPR imaging) using a
      specific monoclonal antibody 11E5 (MAb 11E5) was developed for the detection of
      the seed-borne bacterium Acidovorax avenae subsp. citrulli (Aac), which causes
      fruit blotch in watermelons and cantaloupes, and compared to the conventional
      ELISA technique. The 1:40 mixed self-assembled monolayer (mixed SAM) surface was
      used for the immobilized MAb 11E5 on sensor surface for the detection of Aac.
      Both whole cells and broken cells of Aac were tested by using direct and sandwich
      detection assay. The limit of detection (LOD) of Aac using the SPR imaging
      technique and a direct detection assay was 10(6)cfu/ml and a subsequent
      amplification of the SPR signal using a polyclonal antibody (PAb) lowered the LOD
      to 5*10(5) cfu/ml. The LOD for the ELISA technique was 5*10(4) cfu/ml for the
      detection of Aac, which was slightly better than that for the SPR technique.
      However, the sensor surface based on SPR imaging offered a major advantage in
      terms of surface regeneration, allowing at least five cycles with a shorter time
      assay, multi-channel analysis with an application on multiplex detection, and an
      ease of the surface usage for the detection of Aac in the naturally infected
      plant. The surface was tested against the naturally infected sample and showed
      good selectivity toward the Aac bacteria.

PMID- 21093250
TI  - Food applications of bacterial cell wall hydrolases.
AB  - Bacterial cell wall hydrolases (BCWHs) display a remarkable structural and
      functional diversity that offers perspectives for novel food applications,
      reaching beyond those of the archetype BCWH and established biopreservative hen
      egg white lysozyme. Insights in BCWHs from bacteriophages to animals have
      provided concepts for tailoring BCWHs to target specific pathogens or spoilage
      bacteria, or, conversely, to expand their working range to Gram-negative
      bacteria. Genetically modified foods expressing BCWHs in situ showed successful,
      but face regulatory and ethical concerns. An interesting spin-off development is
      the use of cell wall binding domains of bacteriophage BCWHs for detection and
      removal of foodborne pathogens. Besides for improving food safety or stability,
      BCWHs may also find use as functional food ingredients with specific health
      effects.

PMID- 21093251
TI  - The impact of iron on Listeria monocytogenes; inside and outside the host.
AB  - As iron is vital for all cells, host sequestration of iron provides a significant
      barrier to bacterial infection. The absolute requirement for iron has driven the
      evolution of refined systems by which pathogenic bacteria such as Listeria
      monocytogenes can competitively acquire this element during host infection. This
      process is coordinated, at least partly, by the Ferric Uptake Regulator (Fur).
      Recent studies have identified loci within the listerial Fur-regulon and have
      characterized specific systems involved in iron uptake from various sources. This
      work has greatly advanced our knowledge of the mechanisms underpinning iron
      homeostasis in L. monocytogenes. A greater understanding of the molecular
      mechanisms by which pathogenic bacteria acquire iron is significant from both a
      food safety and public-health perspective.

PMID- 21093252
TI  - The dosimetric effect of zipper artifacts on tomotherapy adaptive dose
      calculation--a phantom study.
AB  - Tomotherapy adaptive dose calculation offers the ability to verify and adjust the
      therapeutic plan during the treatment. Using tomotherapy adaptive dose
      calculation, the planned fluence pattern can be used to recalculate the dose
      distribution on pretreatment megavoltage computed tomography (MVCT) images.
      Zipper artifacts, which appear as increased density in the central region of MVCT
      images, may affect the accuracy of adaptive dose recalculation. The purpose of
      this study was to evaluate the dosimetric effects of zipper artifacts on
      tomotherapy adaptive dose calculation. MVCT images of a cylindrical water phantom
      of 22-cm diameter were acquired on a tomotherapy system. The zipper artifacts
      were enclosed by a cylindrical planning target volume (PTV) contoured on these
      images. For comparison, artifact-free images were created by replacing the
      computed tomography (CT) numbers of zipper artifacts with the mean CT number of
      water. Treatment plans were generated by giving a uniform dose of 2 Gy to the PTV
      based on these modified images; it was then applied to the images that have the
      zipper artifacts. The impacts of different pitch ratios on the artifacts were
      assessed. The dose distribution differences between the 2 sets of images were
      compared. The absorbed dose that covered 95% volume of PTV and maximum dose,
      minimum dose, and mean dose of the PTV were also calculated and compared. The
      water phantom was scanned on the tomotherapy system twice per week for 12
      consecutive weeks. The mean CT number of zipper artifacts (101 HU) was three
      times higher than that of water (34 HU). The CT number value and location of
      zipper artifacts were not affected by the pitch ratio. Gamma analysis was
      performed between the original and recalculated dose distributions. The
      discrepancies between the isodose distributions calculated by two sets of images
      were within 1%/1-mm tolerance. The dosimetric impact from zipper artifacts was
      found insignificant such that the recalculated dose was underestimated by less
      than 0.5%.

PMID- 21093253
TI  - Cellular senescence: putting the paradoxes in perspective.
AB  - Cellular senescence arrests the proliferation of potential cancer cells, and so
      is a potent tumor suppressive mechanism, akin to apoptosis. Or is it? Why did
      cells evolve an anti-cancer mechanism that arrests, rather than kills, would-be
      tumor cells? Recent discoveries that senescent cells secrete growth factors,
      proteases and cytokines provide a shifting view--from senescence as a cell
      autonomous suppressor of tumorigenesis to senescence as a means to mobilize the
      systemic and local tissue milieu for repair. In some instances, this mobilization
      benefits the organism, but in others it can be detrimental. These discoveries
      provide potential mechanisms by which cellular senescence might contribute to the
      diverse, and seemingly incongruent, processes of tumor suppression, tumor
      promotion, tissue repair, and aging.

PMID- 21093255
TI  - The removal of nutrients from non-point source wastewater by a hybrid bioreactor.
AB  - The aim of this project was to establish an economical and environmentally benign
      biotechnology for removing nutrients from non-point source wastewater. The
      proposal involves a hybrid bioreactor comprised of sequential anaerobic, anoxic
      and aerobic (A(2)/O) processes and an eco-ditch being constructed and applied in
      a suburban area, Kunming, south-western China, where wastewater was discharged
      from an industrial park and suburban communities. The results show that the
      hybrid bioreactor fosters heterotrophic and autotrophic microorganisms. When the
      hydraulic load is 200 m(3) per day with the running mode in 12h cycles, the
      removal efficiencies of the nutrients were 81% for TP, 74% for TDP, 82% for TN,
      79% for NO(3)-N and 86% for NH(4)-N. The improved bacterial community structure
      and bacterial habitats further implied enhanced water quality and indicates that
      the easily-deployed, affordable and environmentally-friendly hybrid bioreactor is
      a promising bio-measure for removing high loadings of nutrients from non-point
      source wastewater.

PMID- 21093254
TI  - Treatment of coal gasification wastewater by a two-continuous UASB system with
      step-feed for COD and phenols removal.
AB  - A two-continuous mesophilic (37 +/- 2 degrees C) UASB system with step-feed was
      investigated as an attractive optimization strategy for enhancing COD and total
      phenols removal of the system and improving aerobic biodegradability of real coal
      gasification wastewater. Through the step-feed period, the maximum removal
      efficiencies of COD and total phenols reached 55-60% and 58-63% respectively in
      the system, at an influent flow distribution ratio of 0.2 and influent COD
      concentration of 2500 mg/L; the corresponding efficiencies were at low levels of
      45-50% and 43-50% respectively at total HRT of 48 h during the single-feed
      period. The maximum specific methanogenic activity and substrate utilization rate
      were 592 +/- 16 mg COD-CH(4)/(g VSS d) and 89 +/- 12 mg phenol/(g VSS d) during
      the step-feed operation. After the anaerobic digestion with step-feed, the
      aerobic effluent COD concentration decreased from 270 +/- 9 to 215 +/- 10 mg/L.
      The results suggested that step-feed enhanced the degradation of refractory
      organics in the second reactor.

PMID- 21093256
TI  - Comparison of polyhydroxyalkanoates production by activated sludges from
      anaerobic and oxic zones of an enhanced biological phosphorus removal system:
      effect of sludge retention time.
AB  - This study compared the PHAs production behavior of sludges from the anaerobic
      and oxic phases of an enhanced biological phosphorus removal (EBPR) system. This
      was accomplished by using the kinetics and stoichiometric coefficients obtained
      from aerobic batch tests to evaluate the performance of these two sludges.
      Experimental results indicated that the metabolic behavior of the sludges for
      PHAs production depend significantly on the operating sludge retention time (SRT)
      of the EBPR system. The oxic sludge with 5 days of SRT exhibited better PHAs
      production performance than anaerobic sludge. Conversely, the anaerobic sludge
      with 15 days of SRT had superior PHAs production capability compared to oxic
      sludge. These comparisons suggest that whether anaerobic or oxic sludge should be
      employed for PHAs production depends mainly on the operating SRT of the EBPR
      system.

PMID- 21093257
TI  - Fractal kinetic analysis of polymers/nonionic surfactants to eliminate lignin
      inhibition in enzymatic saccharification of cellulose.
AB  - The profile of enzymatic saccharification of Avicel in the presence and absence
      of lignin has been described with a fractal kinetic model (Wang and Feng, 2010),
      in which the retarded hydrolysis rate of enzymatic saccharification of cellulose
      has been represented with a fractal exponent. The lignin inhibition in the
      enzymatic saccharification of cellulose is indexed by the increase of fractal
      exponent, which can not be fully counterbalanced by high cellulase loading due to
      the high fractal exponent at high cellulase loading. On the contrary, fractal
      kinetic analysis indicates that an addition of some nonionic surfactant/polymers
      decrease the fractal exponent to the original values of enzymatic
      saccharification of Avicel without lignin and the corresponding toxicity of
      nonionic surfactants/polymers on the consecutive ethanol fermentation strain
      Saccharomyces cerevisiae is also examined.

PMID- 21093258
TI  - Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide
      derivatives as potent 11beta-HSD1 inhibitors.
AB  - The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide
      inhibitors of 11beta-HSD1 are described. Optimization rapidly led to potent,
      highly selective, and orally bioavailable inhibitors demonstrating efficacy in
      both rat and non-human primate ex vivo pharmacodynamic models.

PMID- 21093259
TI  - Synthesis and 11beta hydroxysteroid dehydrogenase 1 inhibition of thiazolidine
      derivatives with an adamantyl group.
AB  - A new series of thiazolidine derivatives with an adamantyl group was synthesized
      and evaluated for their ability to inhibit 11beta-hydroxysteroid dehydrogenase 1
      (11beta-HSD1). Our initial compound 5a showed a weak inhibitory activity.
      Significant improvements in potency were achieved by substituent modification.
      The potent compound 8g (E) showed good in vitro inhibitory activity toward human
      11beta-HSD1, selectivity toward 11beta-HSD2, metabolic stability,
      pharmacokinetic, and safety profile. Furthermore, this compound significantly
      inhibited 11beta-HSD1 activity in rat and monkey models, and showed improved
      glycemic control in KKAy mice.

PMID- 21093260
TI  - Clinical characteristics and outcomes of bilateral breast cancer in an Australian
      cohort.
AB  - PURPOSE: Uncertainty remains about the impact of bilateral breast cancer.
      Characteristics and outcomes of unilateral and bilateral breast cancer were
      compared within an Australian multi-institutional cohort. METHODS: Demographic,
      tumour and treatment characteristics were compared among unilateral (n = 2336)
      and bilateral cases (52 synchronous, 35 metachronous) using descriptive analyses.
      Disease-specific outcomes were investigated using Cox regression modelling to
      adjust for prognostic and treatment factors. RESULTS: Factors associated with
      increased risk of bilateral breast cancer included lobular histology (p = 0.046),
      family history (p = 0.025) and metropolitan residence (p = 0.006). Mastectomy was
      more common for bilateral cases (p = 0.001) while radiotherapy was less common (p
      = 0.015). Index metachronous cases were less likely to receive hormonal therapy
      (p = 0.001). Five-year survivals for metachronous, synchronous and unilateral
      cases were 79%, 88% and 94%, respectively. Poorer outcomes remained after
      adjusting for prognostic factors [HR = 2.26, 1.21-4.21]. CONCLUSION: Our results
      confirm international findings indicating worse outcomes from bilateral compared
      with unilateral breast cancer.

PMID- 21093261
TI  - Social bonds enhance reproductive success in male macaques.
AB  - For animals living in mixed-sex social groups, females who form strong social
      bonds with other females live longer and have higher offspring survival [1-3].
      These bonds are highly nepotistic, but sometimes strong bonds may also occur
      between unrelated females if kin are rare [2, 3] and even among postdispersal
      unrelated females in chimpanzees and horses [4, 5]. Because of fundamental
      differences between the resources that limit reproductive success in females
      (food and safety) and males (fertilizations), it has been predicted that bonding
      among males should be rare and found only for kin and among philopatric males [6]
      like chimpanzees [7-9]. We studied social bonds among dispersing male Assamese
      macaques (Macaca assamensis) to see whether males in multimale groups form
      differentiated social bonds and whether and how males derive fitness benefits
      from close bonds. We found that strong bonds were linked to coalition formation,
      which in turn predicted future social dominance, which influenced paternity
      success. The strength of males' social bonds was directly linked to the number of
      offspring they sired. Our results show that differentiated social relationships
      exert an important influence on the breeding success of both sexes that
      transcends contrasts in relatedness.

PMID- 21093262
TI  - Inhibition of respiration extends C. elegans life span via reactive oxygen
      species that increase HIF-1 activity.
AB  - A mild inhibition of mitochondrial respiration extends the life span of many
      organisms, including yeast, worms, flies, and mice, but the underlying mechanism
      is unknown. One environmental condition that reduces rates of respiration is
      hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play
      a role in the longevity response to reduced respiration. The hypoxia-inducible
      factor HIF-1 is a highly conserved transcription factor that activates genes that
      promote survival during hypoxia. In this study, we show that inhibition of
      respiration in C. elegans can promote longevity by activating HIF-1. Through
      genome-wide screening, we found that RNA interference (RNAi) knockdown of many
      genes encoding respiratory-chain components induced hif-1-dependent
      transcription. Moreover, HIF-1 was required for the extended life spans of clk-1
      and isp-1 mutants, which have reduced rates of respiration. Inhibiting
      respiration appears to activate HIF-1 by elevating the level of reactive oxygen
      species (ROS). We found that ROS are increased in respiration mutants and that
      mild increases in ROS can stimulate HIF-1 to activate gene expression and promote
      longevity. In this way, HIF-1 appears to link respiratory stress in the
      mitochondria to a nuclear transcriptional response that promotes longevity.

PMID- 21093263
TI  - Disrupting parietal function prolongs dominance durations in binocular rivalry.
AB  - Human brain imaging studies of bistable perceptual phenomena revealed that
      frontal and parietal areas are activated during perceptual switches between the
      two conflicting percepts. However, these studies do not provide information about
      causality, i.e., whether activity reports a consequence or a cause of the
      perceptual change. Here we used functional magnetic resonance imaging to
      individually localize four parietal regions involved in perceptual switches
      during binocular rivalry in 15 subjects and subsequently disturbed their neural
      processing and that of a control site using 2 Hz repetitive transcranial magnetic
      stimulation (TMS) during binocular rivalry. We found that TMS over one of the
      sites, the right intraparietal sulcus (IPS), prolonged the periods of stable
      percepts. Additionally, the more lateralized the blood oxygen level-dependent
      signal was in IPS, the more lateralized the TMS effects were. Lateralization
      varied considerably across subjects, with a right-hemispheric bias. Control
      replay experiments rule out nonspecific effects of TMS on task performance,
      reaction times, or eye blinks. Our results thus demonstrate a causal,
      destabilizing, and individually lateralized effect of normal IPS function on
      perceptual continuity in rivalry. This is in accord with a role of IPS in
      perceptual selection, relating its role in rivalrous perception to that in
      attention.

PMID- 21093264
TI  - Evidence that meiotic sex chromosome inactivation is essential for male
      fertility.
AB  - The mammalian X and Y chromosomes share little homology and are largely
      unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and
      Y-linked genes, or meiotic sex chromosome inactivation (MSCI). Whether MSCI is
      essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed
      in mouse mutants in which MSCI fails, e.g., Brca1(-/-), H2afx(-/-), Sycp1(-/-),
      and Msh5(-/-). However, these also harbor defects in synapsis and/or
      recombination and as such may activate a putative pachytene checkpoint. Here we
      present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY
      males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without
      accompanying synapsis/recombination defects. We find that XYY males, like
      synapsis/recombination mutants, display pachytene arrest and that this can be
      circumvented by preventing Y-Y synapsis and associated Y gene expression.
      Pachytene expression of individual Y genes inserted as transgenes on autosomes
      shows that expression of the Zfy 1/2 paralogs in XY males is sufficient to
      phenocopy the pachytene arrest phenotype; insertion of Zfy 1/2 on the X
      chromosome where they are subject to MSCI prevents this response. Our findings
      show that MSCI is essential for male meiosis and, as such, provide insight into
      the differential severity of meiotic mutations' effects on male and female
      meiosis.

PMID- 21093265
TI  - Adaptive divergence in the thyroid hormone signaling pathway in the stickleback
      radiation.
AB  - During adaptive radiations, animals colonize diverse environments, which requires
      adaptation in multiple phenotypic traits. Because hormones mediate the dynamic
      regulation of suites of phenotypic traits, evolutionary changes in hormonal
      signaling pathways might contribute to adaptation to new environments. Here we
      report changes in the thyroid hormone signaling pathway in stream-resident
      ecotypes of threespine stickleback fish (Gasterosteus aculeatus), which have
      repeatedly evolved from ancestral marine ecotypes. Stream-resident fish exhibit a
      lower plasma concentration of thyroid hormone and a lower metabolic rate, which
      is likely adaptive for permanent residency in small streams. The thyroid
      stimulating hormone-beta2 (TSHbeta2) gene exhibited significantly lower mRNA
      expression in pituitary glands of stream-resident sticklebacks relative to marine
      sticklebacks. Some of the difference in TSHbeta2 transcript levels can be
      explained by cis-regulatory differences at the TSHbeta2 gene locus. Consistent
      with these expression differences, a strong signature of divergent natural
      selection was found at the TSHbeta2 genomic locus. By contrast, there were no
      differences between the marine and stream-resident ecotypes in mRNA levels or
      genomic sequence in the paralogous TSHbeta1 gene. Our data indicate that
      evolutionary changes in hormonal signaling have played an important role in the
      postglacial adaptive radiation of sticklebacks.

PMID- 21093266
TI  - Zygotic resetting of the HISTONE 3 variant repertoire participates in epigenetic
      reprogramming in Arabidopsis.
AB  - In most eukaryotes, the HISTONE 3 family comprises several variants distinguished
      by their amino acid sequence, localization, and correlation with transcriptional
      activity. Transgenerational inheritance of epigenetic information carried by
      histones is still unclear. In addition to covalent histone modifications, the
      mosaic distribution of H3 variants onto chromatin has been proposed to provide a
      new level of epigenetic information. To study the transmission of patterns of H3
      variants through generations, we combined transcriptional profiling and live
      imaging of the 13 H3 variants encoded by the Arabidopsis plant genome. In
      comparison with somatic cells, only a restricted number of H3 variants are
      present in male and female gametes. Upon fertilization, H3 variants contributed
      by both gametes are actively removed from the zygote chromatin. The somatic H3
      composition is restored in the embryo by de novo synthesis of H3 variants. A
      survey of Arabidopsis homologs of animal H3 chaperones suggests that removal of
      parental H3 from the zygote nucleus relies on a new mechanism. Our results
      suggest that reprogramming of parental genomes in the zygote limits the
      inheritance of epigenetic information carried by H3 variants across generations.

PMID- 21093267
TI  - Specialization of a Drosophila capping protein essential for the protection of
      sperm telomeres.
AB  - BACKGROUND: A critical function of telomeres is to prevent fusion of chromosome
      ends by the DNA repair machinery. In Drosophila somatic cells, assembly of the
      protecting capping complex at telomeres notably involves the recruitment of HOAP,
      HP1, and their recently identified partner, HipHop. We previously showed that the
      hiphop gene was duplicated before the radiation of the melanogaster subgroup of
      species, giving birth to K81, a unique paternal effect gene specifically
      expressed in the male germline. RESULTS: Here we show that K81 specifically
      associates with telomeres during spermiogenesis, along with HOAP and HP1, and is
      retained on paternal chromosomes until zygote formation. In K81 mutant testes,
      capping proteins are not maintained at telomeres in differentiating spermatids,
      resulting in the transmission of uncapped paternal chromosomes that fail to
      properly divide during the first zygotic mitosis. Despite the apparent similar
      capping roles of K81 and HipHop in their respective domain of expression, we
      demonstrate by in vivo reciprocal complementation analyses that they are not
      interchangeable. Strikingly, HipHop appeared to be unable to maintain capping
      proteins at telomeres during the global chromatin remodeling of spermatid nuclei.
      CONCLUSIONS: Our data demonstrate that K81 is essential for the maintenance of
      capping proteins at telomeres in postmeiotic male germ cells. In species of the
      melanogaster subgroup, HipHop and K81 have not only acquired complementary
      expression domains, they have also functionally diverged following the gene
      duplication event. We propose that K81 specialized in the maintenance of telomere
      protection in the highly peculiar chromatin environment of differentiating male
      gametes.

PMID- 21093268
TI  - Visiting policies in the adult intensive care units: a complete survey of Dutch
      ICUs.
AB  - OBJECTIVES: Treatment in an intensive care unit (ICU) is not only very stressful
      for the patient but also for the family as well. An open visiting policy, defined
      as a policy that imposes no restrictions on visiting hours, duration of visits
      and/or number of visitors, seems to fit very well both patient and family needs.
      The purpose of this article is to give an overview of the current situation of
      Dutch ICUs visiting policies. DESIGN: Nationwide, telephone-based questionnaire
      survey. PARTICIPANTS: (Head)nurses of all ICUs. RESULTS: The results of this
      study show that none of the ICUs have an open visiting policy, defined as a
      policy that imposes no restrictions on visiting time, duration of visits and/or
      number of visitors. The majority of the Dutch ICUs (85.7%) has restricted
      visiting policies. Responses were obtained from 100% of the ICUs. CONCLUSION:
      Despite several international guidelines, research and literature about
      unrestricted visiting hours on the ICUs, none of the ICUs in this study operates
      with such a visiting policy. If we take these results into account then the
      question rises if ICUs are aware of these patients and family needs on the ICUs.

PMID- 21093269
TI  - Unicompartmental knee arthroplasties implanted for osteoarthritis with partial
      loss of joint space have high re-operation rates.
AB  - The indications and contraindications for unicompartmental knee arthroplasty
      (UKA) are controversial. The aim of the study was to determine the risk factors
      for re-operation in our practice. A series of 113 medial UKAs with mean follow-up
      of 63 months were reviewed retrospectively. Pre-operatively all knees had
      radiographic or arthroscopic evidence of severe cartilage damage. The re
      operation rate was not related to age, gender, arthroscopic finding or body mass
      index. It was related to the joint space on pre-operative standing weight bearing
      radiographs taken in extension. The re-operation rate was 6 (95% CI 2.1-17,
      P<0.001) times higher when the thickness of the pre-operative medial joint space
      was >2 mm rather than <=2 mm. It was 8 (95% CI 2.8-22.5, P<0.001) times higher
      when the thickness of the pre-operative medial space was >40% of the thickness of
      the lateral space. The ratio of pre-operative joint spaces has a greater
      influence on revision rate than the absolute measurement and is independent of
      radiographic magnification or the patient's normal cartilage thickness. We
      therefore recommend that, in medial knee osteoarthritis, UKA should only be used
      if the pre-operative medial joint space on standing radiographs is <=40% of the
      lateral joint space, even if severe cartilage damage is seen arthroscopically.

PMID- 21093270
TI  - Distraction osteogenesis as a salvage method in infected knee megaprostheses.
AB  - Infection of total knee replacement represents a severe complication. Especially
      in cases of infected megaprostheses, treatment options are limited and even
      amputation may become unavoidable. We present two cases of infected knee hinged
      megaprostheses. Both were treated by prosthesis removal and debridement of all
      surrounding infected bone and soft tissue, followed by distraction osteogenesis
      for the bridging of the large bone defect which had resulted. Implant removal and
      surgical debridement were combined with Ilizarov frame application and femoral
      and tibial osteotomies in a one-stage procedure, for commencing distraction
      osteogenesis. After bone transportation was completed, arthrodesis of the knee in
      both cases was successful. Two years after completion of the treatment, both
      patients demonstrate a stable knee arthrodesis and a satisfactory clinical
      result. The described treatment plan represents an effective salvage method in
      cases of infected knee megaprostheses that can successfully address both the need
      for a stable arthrodesis and the avoidance of a severe leg-length discrepancy by
      bridging the extensive bone defect.

PMID- 21093271
TI  - Failures of the Dual Articular knee prosthesis due to fracture of the
      polyethylene post.
AB  - The Dual Articular (DA) total knee replacement was designed for revision and
      complex primary knee arthroplasty. A number of these knees failed due to fracture
      of the polyethylene post. We aimed to identify the proportion of DA prostheses
      that failed in this manner in our hospital. The hospital database was
      interrogated to identify all patients undergoing revision total knee replacement
      under the care of one surgeon from 1995 to 2007. Case notes were then reviewed to
      collect information about the history surrounding the knee surgery, and determine
      the patient's weight at the time of surgery. Telephone follow-up was carried out
      to obtain complete contemporary data. Forty-eight prostheses were implanted into
      39 patients (21 male, 18 female). Thirty-two of the prostheses were DA and of
      these, 7 underwent arthroscopy or arthrotomy to reveal a fracture of the
      polyethylene post (22%). T-tests showed no statistical difference in age (p=0.73)
      or weight (p=0.79) between the group of DA patients with fractured posts and
      those without. Six of the 7 fractures were in male patients (Chi-squared;
      p=0.01). Patients complained of pain, clicking and instability at a mean of 7
      years post-surgery. Sixteen DA2000 prostheses were implanted, but none of these
      had failed due to a fractured polyethylene post. A high proportion of DA
      prostheses failed due to post fracture. We recommend that patients with DA
      prostheses be kept under review to detect failures early. Pain, clicking and
      instability should be investigated with arthroscopy and the tibial insert
      exchanged as appropriate.

PMID- 21093272
TI  - Identification of 3-sulfonylindazole derivatives as potent and selective 5-HT(6)
      antagonists.
AB  - As part of our efforts to develop agents for cognitive enhancement, we have been
      focused on the 5-HT(6) receptor in order to identify potent and selective ligands
      for this purpose. Herein we report the identification of a novel series of 3
      sulfonylindazole derivatives with acyclic amino side chains as potent and
      selective 5-HT(6) antagonists. The synthesis and detailed SAR of this class of
      compounds are reported.

PMID- 21093273
TI  - Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl
      1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.
AB  - The present work describes a series of novel chiral amines that potently inhibit
      the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake
      inhibitors) and were active in vivo in a mouse model predictive of antidepressant
      like activity. The detailed synthesis and in vitro activity and ADME profile of
      compounds is described, which represent a previously undisclosed triple reuptake
      inhibitor chemotype.

PMID- 21093274
TI  - 3D reconstruction and scanning electron microscopy of salivary glands of the
      millipede Rhinocricus padbergi (Verhoef, 1938) (Diplopoda: Spirobolida).
AB  - The three-dimensional technique applied to the salivary gland of the millipides
      Rhinocricus padbergi showed that it is a single structure, dorsolaterally located
      to the animal gut and composed of two distinct portion: an acinar and a tubular
      one. The last one opening onto the oral cavity. This work shows that the salivary
      gland in R. padbergi, although is a single body, it displays two excretory ducts
      (one in each side of the anterior end of the gut) which has the function of
      carrying out the secretion produced toward to the oral cavity, contrary to the
      anterior data registered by other authors who suggested that the salivary gland
      in diplopod animals would be a paired structures.

PMID- 21093275
TI  - Thermoluminescence analysis of co-doped NaCl at low temperature irradiations.
AB  - The thermoluminescent response and kinetics parameters of NaCl, doubly activated
      by Ca-Mn and Cd-Mn ions, exposed to gamma radiation are analyzed. The doped NaCl
      samples were irradiated at relative low temperature, i.e. at the liquid nitrogen
      temperature (LNT) and at dry ice temperature (DIT), and the glow curves obtained
      after 2 Gy of gamma irradiation were analyzed using the computerized glow curve
      deconvolution (CGCD). An evident variation in the glow curve structure after LNT
      and DIT was observed. It seems that different kinds of trapping levels are
      activated at relative low temperature. The original two prominent peaks in
      compositions A (Ca,Mn) and B (Ca,Mn) have been changed in only one main peak with
      satellites in the low temperature side of the glow curves. In compositions C
      (Cd,Mn) and D (Cd,Mn), low temperature peaks become stronger and prominent than
      the high temperature peaks; this effect could be explained considering that the
      trapping probability for low temperature traps, the one very close to the
      conduction band, is enhanced by low temperatures during irradiation.

PMID- 21093276
TI  - Indoor radon measurements in the city of Valencia.
AB  - The indoor radon risk in Valencia (Spain) was studied more than twenty years ago
      in two surveys using different methodologies and leading to contradictory
      results. We report here on new indoor radon measurements with the charcoal
      canister technique, which confirm the low average level of indoor radon in the
      city, with a geometrical mean of 24 Bq/m(3) and an arithmetic mean of 27 Bq/m(3).

PMID- 21093277
TI  - High specific activity tritiation of several biologically active indoles.
AB  - Methods are presented to synthesize and characterize [(3)H] tryptamine (1b) and
      [(3)H] etodolac (2c).

PMID- 21093278
TI  - Analysis of dose rates received around the storage pool for irradiated control
      rods in a BWR nuclear power plant.
AB  - BWR control rods are activated by neutron reactions in the reactor. The dose
      produced by this activity can affect workers in the area surrounding the storage
      pool, where activated rods are stored. Monte Carlo (MC) models for neutron
      activation and dose assessment around the storage pool have been developed and
      validated. In this work, the MC models are applied to verify the expected
      reduction of dose when the irradiated control rod is hanged in an inverted
      position into the pool.

PMID- 21093279
TI  - ESR dating of calcrete nodules from Bala, Ankara (Turkey): preliminary results.
AB  - The age of two calcrete nodules (C1 and C2) from the Bala section in the region
      of Ankara, Turkey, is determined by the Electron Spin Resonance (ESR) method.
      Three radiation-induced ESR signals at g=2.0056 (A signal), g=2.0006 (C signal)
      and g=2.0038 (broad signal, BL) were observed. The broad signal (BL) intensity
      was used as a dating signal. The properties of this dating signal are described
      in this manuscript. The calcrete nodules were irradiated with a (60)Co gamma
      source and measured with an ESR spectrometer (X-band) to obtain the signal
      intensity vs. dose curve and fitted well with the single exponential saturation
      functions. Based on this model, accumulated dose (D(E)) values for dating are
      obtained using the multiple-aliquot additive dose method. The D(E) values of C1
      and C2 calcretes are 1880+/-207 and 671+/-67 Gy, respectively. The ESR ages of
      the two calcrete samples are obtained by assessing the annual dose rate (D) from
      the content of (238)U, (232)Th and K(2)O determined by wavelength dispersive X
      ray fluorescence (XRF) spectrometry. The results are 761+/-120 and 419+/-64 ka,
      respectively, falling into the Middle Pleistocene Epoch in the geological time
      scale in agreement with the positions of the stratigraphical record.

PMID- 21093280
TI  - Nitric oxide inhibits nitrate reductase activity in wheat leaves.
AB  - Nitrate reductase (NR), a committed enzyme in nitrate assimilation, is involved
      in the generation of nitric oxide (NO) in plants. In wheat leaf segments exposed
      to sodium nitroprusside (SNP) or S-nitrosoglutathione (GSNO), NR activity was
      significantly reduced to different degrees between 3 and 21 h, whereas its
      activity was partially recovered when the NO scavenger cPTIO was used. At 21 h,
      NR activity decreased from 38% with 10 MUM SNP to 91% with 500 MUM SNP, respect
      to the C values. S-nitrosoglutathione reduced NR activity between 18% and 26%
      only at 3 h. When added directly to the incubation solution, NR activity was
      quickly and strongly inhibited more than 90% by 10 or 50 MUM SNP, whereas 10 MUM
      GSNO reduced the enzyme activity an average of 50%, at 30 min of incubation. l
      NAME and d-arginine (nitric oxide synthase (NOS) inhibitors) increased NR
      activity by 14% and 52% respectively, at 21 h of exposure, leading us to suppose
      that endogenous NOS-dependent NO formation could also be modulating NR activity.
      NR protein expression was not affected by 10 or 100 MUM SNP at 3 or 21 h of
      incubation, whereas nitration of tyrosines was not detected in the NR protein.
      Nitrates, which content increased along the time in the tissues, could be
      exerting a role in this regulation.

PMID- 21093281
TI  - Differential occurrence of oxidative burst and antioxidative mechanism in
      compatible and incompatible interactions of Solanum lycopersicum and Ralstonia
      solanacearum.
AB  - Striking increase in reactive oxygen species (ROS) such as hydrogen peroxide
      (H(2)O(2)) has been demonstrated to occur in plants in response to pathogen
      attack. The aim of this study was to investigate the biochemical aspects of ROS
      generation, antioxidative mechanism and cell wall reinforcement as responses of
      tomato cultivars Arka Meghali (AM; susceptible) and BT-10 (BT; resistant) against
      Ralstonia solanacearum (Ralsol). While the oxidative burst was characterized by a
      single phase ROS increase in AM, there was a clear bi-phasic ROS generation in
      BT. The first significant increase of H(2)O(2) production was noticed at 12 h
      post-inoculation (hpi) followed by a sharp increase in H(2)O(2) generation after
      36 hpi. Lipid peroxidation was more in roots of AM than that of BT after pathogen
      inoculation. Superoxide dismutase and catalase activities were continuously at
      very high level in Ralsol-inoculated BT plants, whereas activities of the enzymes
      were observed to decrease at later stage in Ralsol-inoculated AM plants. Guaiacol
      peroxidase activity was high in Ralsol-inoculated roots of both cultivars, but BT
      recorded much higher activity than AM. Higher activity of ascorbate peroxidase in
      inoculated BT might be an indication of better scavenging activity of the enzyme.
      Total phenolic content and lignin deposition were significantly higher in Ralsol
      inoculated BT compared to inoculated AM. Our results indicate that increased
      level of ROS production coupled with more efficient antioxidative system, lower
      rate of lipid peroxidation and high lignin deposition in cell wall may contribute
      to the resistance of tomato plants to Ralsol.

PMID- 21093282
TI  - Microalbuminuria is associated with high adverse event rate following cardiac
      surgery.
AB  - OBJECTIVE: To examine if preoperative microalbuminuria is associated with an
      increased risk of long-term adverse outcomes following elective cardiac surgery
      and if it provides additional prognostic information beyond the European System
      for Cardiac Operative Risk Evaluation (EuroSCORE). METHODS: In a prospective
      follow-up study, we included 1049 patients undergoing elective cardiac surgery
      from 1 April 2005 to 30 September 2007. Microalbuminuria (urine
      albumin/creatinine ratio between 2.5 and 25 mg mmol(-1)) was assessed
      preoperatively in a morning spot-urine sample. We used population-based medical
      registries for follow-up from day 31 until day 365 postoperatively, and compared
      all-cause death, myocardial infarction, cerebral stroke and a composite outcome
      of severe infections including septicaemia, deep or superficial sternal wound
      infection, or leg wound infection among patients with or without microalbuminuria
      using Cox proportional hazard and competing risk regressions. RESULTS:
      Microalbuminuria was found in 175 (18.5%) out of 947 patients available for
      follow-up. The adjusted risks of all-cause death (adjusted hazard ratio 2.3 (95%
      confidence interval 1.1-4.9)), stroke (adjusted hazard ratio 2.9 (95% confidence
      interval 1.1-7.8)) and severe infection composite outcome (adjusted hazard ratio
      2.4 (95% confidence interval 1.2-4.9)) were doubled to tripled in patients with
      preoperative microalbuminuria. The risk of myocardial infarction was not
      increased. Adding information on microalbuminuria improved the predictive
      accuracy of the EuroSCORE regarding mortality (areas under receiver operating
      characteristic curves were: for the EuroSCORE 0.73 (95% confidence interval 0.65
      0.81) and for EuroSCORE+microalbuminuria 0.76 (95% confidence interval 0.68
      0.83). CONCLUSIONS: Preoperative microalbuminuria is associated with an increased
      risk of long-term adverse outcomes in patients undergoing elective cardiac
      surgery, and it appears to provide prognostic information on mortality.

PMID- 21093283
TI  - Thymoma: inter-relationships among World Health Organization histology, Masaoka
      staging and myasthenia gravis and their independent prognostic significance: a
      single-centre experience.
AB  - OBJECTIVE: In thymomas, World Health Organization (WHO) histology, Masaoka stage
      and myasthenia gravis (MG) have long been considered important for patient
      management and outcome. Their role has been independently investigated in the
      past. Few studies, however, focussed on the correlations among these variables.
      The aim of the present study was to retrospectively evaluate, in our patient
      population of resected thymomas, the inter-relationships among MG, WHO histology
      and Masaoka stage, and to look at how and to what extent one variable is
      associated with the other two in terms of clinical presentation and survival.
      METHODS: From January 1990 to October 2008, 255 patients received resection of
      thymoma. MG was present in 105 cases (41%). Histology by WHO was: 25 A (10%), 72
      AB (28%), 65 B1 (25%), 69 B2 (27%) and 24 B (9%). Masaoka staging was stage I, 54
      cases (21%), stage II, 86(34%), stage III 79 (31%), and stage IVA 36 (14%).
      Ordinal and logistic regression models were undertaken to analyse correlations
      among ordinal (WHO histology and Masaoka stage) and categorical (MG, A vs B WHO
      types) variables. Univariate and multivariate survival analysis were also
      performed using the same covariates. Overall survival (OS) and disease-free
      survival (DFS) were calculated. RESULTS: MG was associated with early Masaoka
      stages (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33-0.62) and B-type
      thymomas (OR 1.59, 95% CI 1.23-2.05). B-type thymomas were associated with high
      Masaoka stage (OR 0.46, 95% CI 0.36-0.60). High Masaoka stage was associated with
      non-MG (OR 3.27; 95% CI 2.00-5.34). In univariate survival analysis, MG (p =
      0.01) and Masaoka stage (p = 0.0001) were significant prognostic indicators using
      OS. Using DFS, WHO histology (A/AB vs B1/B2/B3 types) (p = 0.05) and Masaoka
      stage (p = 0.0001) had a prognostic significance. In multivariate analysis, only
      Masaoka stage was an independent prognostic covariate using OS (hazard ratio (HR)
      2.57, 95% CI 1.46-4.52, p = 0.001) and DFS (HR 3.18, 95% CI 1.56-6.52, p =
      0.001). CONCLUSIONS: In thymomas, MG, WHO histology and Masaoka stage are inter
      related. MG has an influence on histology and stage at presentation, while two
      clinical/histologic patterns are more likely: early Masaoka stage A/AB WHO type
      and high Masaoka stage/B WHO type. Among the three factors, only Masaoka stage
      had a prognostic significance on OS and DFS. Our results suggest that a
      consistent staging system for thymomas should take into account all three
      variables.

PMID- 21093284
TI  - Thromboelastography-platelet mapping expanding in non-cardiac surgery.

PMID- 21093285
TI  - Mathematical relationship between cytokine concentrations and pathogen levels
      during infection.
AB  - The relationship between concentrations of cytokines and microbial pathogen
      levels during infection is not clear. In a sub-lethal murine infection model
      using Gram-negative bacterial pathogen Yersinia pseudotuberculosis, the serum
      concentrations (C) of pro-inflammatory cytokines tumor necrosis factor alpha
      (TNFalpha), interferon gamma (IFNgamma), interleukine-1beta (IL-1beta) and
      interleukine-18 (IL-18) formed a mathematical relationship with the splenic
      pathogen levels (P) as measured by colony forming unit. Naming parameters "m" and
      "k" for magnitude and kinetics, respectively, the relationship is depicted as
      C=mP(k). When reanalyzing the TNFalpha and IFNgamma concentrations and the
      bacterial levels that were determined by other groups during infection with
      another strain of Y. pseudotuberculosis or with Yersinia pestis, this
      relationship was maintained. Interestingly, the changes in the values of "m" and
      "k" were consistent with the progress of the host immune response during
      infection; while deviation from this relationship was observed in individuals
      that seemed to be unable to control infection. Furthermore, in a murine model of
      ricin intoxication the local concentrations of the cytokine monocyte chemotactic
      protein 1 (MCP-1) and the concentrations of injected castor bean toxin ricin also
      conform to this relationship. C=mP(k) could be a general relationship in host
      cytokine response to pathogens or pathogen-associated molecular patterns. If
      confirmed, this type of analysis will be very useful in identifying the steps in
      a host immune response with which a pathogen interferes. It will also help to
      determine the specific functions of a host factor in the immune response.

PMID- 21093286
TI  - Effect of omega-3 fatty acids on plasma level of 8-isoprostane in kidney
      transplant patients.
AB  - OBJECTIVE: It has been shown previously that the serum level of F2-isoprostanes
      acts as an indicator of oxidative stress, which is a risk factor for vascular
      disease especially in end-stage renal disease. It is not known whether n-3
      polyunsaturated fatty acids can decrease oxidative stress in renal recipient
      patients. DESIGN, SETTING, AND SUBJECTS: In this single blind, randomized,
      placebo-controlled study, the effect of 3 and 6 months of fish oil administration
      on 8-isoprostane levels in renal transplant recipients was evaluated.
      INTERVENTION: Twenty-two renal transplant patients who fulfilled inclusion and
      exclusion criteria randomly received either fish oil dietary supplementation, 6
      g/day (720 mg of DHA and 1,080 mg of EPA) or placebo for 6 months. MAIN OUTCOME
      MEASURE: Serum 8-isoprostane concentration was measured as markers of oxidative
      stress. RESULTS: A significant decrease in 8-isoprostane levels was observed only
      in the placebo group after transplantation compared to baseline (P < 0.05).
      However, the group receiving fish oil had a significantly lower cholesterol level
      than that of the placebo group (P < 0.05). CONCLUSION: On the basis of our
      results, omega-3 fatty acids supplementation decreased the beneficial effects of
      kidney transplantation on oxidative stress.

PMID- 21093287
TI  - Handgrip strength as a simple indicator of possible malnutrition and inflammation
      in men and women on maintenance hemodialysis.
AB  - OBJECTIVE: To assess the validity of handgrip strength (HGS) as a simple
      screening instrument for malnutrition and inflammation in patients on maintenance
      hemodialysis (MHD) by correlating it with malnutrition-inflammation score (MIS).
      DESIGN: Cross-sectional analysis of the Prospective Study of the Prognosis in
      Chronic Hemodialysis Patients (PROHEMO). SETTING: Satellite dialysis units in the
      city of Salvador, Brazil. PATIENTS: The sample included 274 men and 162 women on
      MHD. MAIN PREDICTOR VARIABLE: HGS was chosen as the main predictor variable in
      this study. MAIN OUTCOME MEASURE: An MIS >=6. RESULTS: As compared with men,
      women were found to have lower HGS values (19.38 +/- 6.48 kg vs. 29.07 +/- 8.67
      kg; P < .001) and higher MIS (6.38 +/- 3.84 vs. 5.57 +/- 3.39; P = .032). HGS was
      found to be inversely correlated with MIS among women (Spearman's rho = -.360; P
      < .001) as well as men (Spearman's rho = -0.384; P < .001); this inverse
      correlation was observed in patients with and without diabetes, different racial
      groups, younger and older subjects, incident (<3 months) and prevalent patients,
      in the case of both genders. Among both men and women, every one standard
      deviation lower of HGS was associated with more than two-fold higher odds for MIS
      >=6, after adjusting for age, race, duration of dialysis, and Kt/V. These
      associations remained statistically significant after more extensive adjustments.
      The optimized cutoff point of HGS for MIS >=6 was 28.3 kg for men (sensitivity =
      70.0%; specificity = 66.0%) and 23.4 kg for women (sensitivity = 87.0%;
      specificity = 43.0%). CONCLUSIONS: Lower HGS values were independently associated
      with higher MIS among patients on MHD across several subgroups. These results
      suggest that HGS is a valid screening instrument for malnutrition and
      inflammation in patients on MHD.

PMID- 21093288
TI  - Association of zinc deficiency and depression in the patients with end-stage
      renal disease on hemodialysis.
AB  - INTRODUCTION: Depression is a common psychological symptom in patients undergoing
      chronic hemodialysis. In the general population, low serum zinc level is
      associated with major depression. The current study surveys the possible
      relationship between the prevalence of depression and plasma level of zinc in
      patients on hemodialysis (HD). PATIENTS AND METHODS: A total of 135 patients with
      end-stage renal disease (ESRD) on HD were enrolled in the study. The severity of
      depression was assessed using Beck Depression Inventory (BDI). Plasma zinc level
      was measured from fasting samples. RESULTS: Mean age of the patients was 52.45
      (standard deviation: 15.33) years. In all, 76% of the patients had some degree of
      depression according to BDI scoring system (BDI >14). The mean level of plasma
      zinc in the depressed patients was significantly lower than the rest of the
      patients (67.46 +/- 29.7 vs. 85.26 + 40.05). DISCUSSION: Zinc deficiency may be a
      reversible cause which might contribute to the increased rate of depression in HD
      patients. This is the first study reporting the association of zinc deficiency
      with the presence of depression in HD patients; therefore, these findings need
      further investigations.

PMID- 21093289
TI  - Ascending aortic pseudoaneurysm.

PMID- 21093290
TI  - Postoperative hypoalbuminemia is associated with outcome in patients undergoing
      off-pump coronary artery bypass graft surgery.
AB  - OBJECTIVE: The authors aimed to investigate whether immediate postoperative
      hypoalbuminemia could be associated with outcomes after off-pump coronary artery
      bypass graft (OPCAB) surgery. DESIGN: A retrospective analysis of the medical
      data. SETTING: Cardiac operating room and adult cardiovascular intensive care
      unit at a single institution. PARTICIPANTS: Six hundred ninety adult patients
      underwent elective OPCAB surgery over a 30-month period. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: To evaluate the clinical relevance of immediate
      postoperative hypoalbuminemia, the lowest serum albumin level measured over the
      first 12 hours postoperatively was recorded. A cutoff point was calculated by the
      area under the curve in the receiver operating characteristic plot for 30-day
      adverse events including death. Patients were classified according to the cutoff
      value, and outcomes were compared between groups using propensity score-matching
      analysis. The impact of immediate postoperative hypoalbuminemia on OPCAB outcome
      was investigated using multivariate analysis. The cutoff value for immediate
      postoperative albumin concentration for predicting 30-day adverse events was 2.3
      g/dL. Immediate postoperative hypoalbuminemia (<2.3 g/dL) was associated
      independently with postoperative respiratory failure (odds ratio [OR] = 8.85, p =
      0.04), wound infection (OR = 4.44, p = 0.04), the need for an intra-aortic
      balloon pump after the operation (OR = 13.7, p = 0.02), renal failure (OR = 7.98,
      p = 0.01), reoperation for bleeding (OR = 4.33, p = 0.05), and the need for
      inotropes in the intensive care unit (OR = 1.79, p = 0.02). CONCLUSIONS:
      Immediate postoperative hypoalbuminemia was associated with poorer outcomes in
      OPCAB patients. Monitoring of albumin levels after OPCAB could identify patients
      at risk for short-term adverse events.

PMID- 21093291
TI  - Parachute-like asymmetric mitral valve associated with mitral valve cleft and
      atrial septal defect in an adult.

PMID- 21093292
TI  - Transcatheter aortic valve implantation for high-risk patients does not reduce
      mortality compared with predicted.

PMID- 21093293
TI  - Pulse contour analysis to assess hemodynamic response to passive leg raising.
AB  - OBJECTIVE: The authors evaluated the ability of 2 pulse contour cardiac output
      (CO) techniques to track CO changes during passive leg raising (PLR) to assess
      fluid loading responsiveness. DESIGN: A prospective study. SETTING: An intensive
      care unit in a university hospital. PARTICIPANTS: Twenty mechanically ventilated
      postoperative cardiac surgery patients. INTERVENTIONS: Thirty-degree PLR.
      MEASUREMENTS AND MAIN RESULTS: The authors estimated CO by 3 techniques:
      thermodilution (COtd), arterial pulse power (Coli; LiDCO, London, UK), and pulse
      contour method (Com; FMS, Amsterdam, The Netherlands) based on uncalibrated
      Modelflow. The authors measured heart rate (HR), central venous pressure,
      arterial pulse pressure (PP), systolic pressure (SP), and mean arterial pressure
      (MAP). Stroke volume (SV), SP, PP, and SV variation (PPV and SVV, respectively)
      were calculated over 5 breaths. SVV was measured by both LiDCO (SVVli) and
      Modelflow (SVVm) devices. PLR-induced changes in COtd correlated with COli (p <
      0.001) and COm (p < 0.001). Preload dependence was predicted with an area under
      the ROC curve of 0.968 for DeltaCOm, 0.841 for DeltaCOli, 0.825 for SVVm, 0.873
      for SVVli, 0.808 for PPV, 0.778 for DeltaSP, 0.714 for DeltaPP, and 0.873 for
      DeltaMAP. CONCLUSIONS: Changes in COm, COli, SVV, and PPV track COtd changes
      during PLR with a high degree of accuracy in sedated, ventilated, postoperative
      cardiac surgery patients. Changes in pulse contour CO after PLR can be used to
      predict fluid loading responsiveness.

PMID- 21093294
TI  - Acute intraoperative pulmonary embolism: an unusual cause of hypoxemia during one
      lung ventilation.

PMID- 21093295
TI  - One-lung anesthesia alters the magnitude of aortic regurgitation because of a
      reduction in intrathoracic pressure.

PMID- 21093296
TI  - Aortic valve stenosis and von Willebrand disease: a clinical condition without
      full explanation.

PMID- 21093297
TI  - Perioperative management of endovascular abdominal aortic aneurysm repair: update
      2010.

PMID- 21093298
TI  - Attenuation of early airway obstruction by mesenchymal stem cells in a murine
      model of heterotopic tracheal transplantation.
AB  - BACKGROUND: Long-term success in lung transplantation is limited by obliterative
      bronchiolitis (OB). Presently, complete understanding of the mechanisms of OB has
      been elusive. Bone marrow-derived mesenchymal stem cells (MSC) have been shown to
      modulate repair of the injured lung in multiple disease models. We hypothesized
      that the injection of MSC would prevent development of early airway obstruction
      (AO) in the heterotopic tracheal transplant model. METHODS: Forty-four tracheas
      from BALB/c and C57BL/6 donors were transplanted into 22 C57BL/6 recipients. At
      the time of transplant, 13 of the allogeneic recipient mice were injected with 5
      * 10(5) MSC from various murine sources. To confirm the role of the immune
      response in the generation of AO we used a permeable inhibitor of nuclear factor
      kappaB (NF-kappaB) in 11 recipients after transplantation with 22 BALB/c
      tracheas. RESULTS: After transplantation, administration of MSC inhibited
      intraluminal obstruction by collagen in 98% of the mice and transforming factor
      beta (TGF-beta) expression decreased to levels similar to those observed in
      isograft controls. These effects were associated with a significant (p < 0.05)
      increase in expression of the anti-inflammatory cytokine interleukin-10 (IL-10).
      NF-kappaB inhibitor showed decreased expression of transforming growth factor
      beta (TGF-beta) in the Day 7 and Day 14 groups, resulting in a 60% reduction of
      luminal obstruction as well as a decrease in inflammatory cells to the airway.
      CONCLUSION: Our observations suggest that administration of MSC prevents
      development of airway occlusion in a mouse model, probably through the modulated
      immune response altering TGF-beta expression.

PMID- 21093299
TI  - The Heart Failure Survival Score outperforms the peak oxygen consumption for
      heart transplantation selection in the era of device therapy.
AB  - BACKGROUND: The peak oxygen consumption (VO(2)) and the Heart Failure Survival
      Score (HFSS) risk stratify patients with chronic heart failure (CHF) referred for
      heart transplantation. However, these tools were developed before widespread use
      of implantable cardioverter defibrillator (ICD) and cardiac resynchronization
      therapy (CRT). The prognostic accuracy of these tools in patients with ICD and/or
      CRT is unknown. METHODS: Cardiopulmonary exercise testing with measurement of
      peak VO(2) and calculation of the HFSS was done in 715 CHF patients (54 +/- 12
      years; ICD, 244; CRT, 30; CRT-D, 108; none, 333) referred for heart
      transplantation. RESULTS: During an average follow-up of 962 +/- 912 days, 354
      patients died or received urgent heart transplant or left ventricular assist
      device. By Cox hazard analysis, both peak VO(2) and HFSS were powerful
      independent prognostic markers. By Kaplan-Meier analysis, the HFSS was effective
      in discriminating patients into low-, medium-, and high-risk groups in all device
      groups. In contrast, the peak VO(2) did not discriminate between low (>14
      ml/min/kg) and medium (10.1 to 14 ml/min/kg) risk in device patients. By area
      under the receiver operating characteristic curve, the HFSS performed better than
      the peak VO(2) (1-year in total cohort; 0.72 vs. 0.65; p < 0.001; 1-year in
      device patients; 0.69 vs. 0.65; p < 0.001). CONCLUSION: The HFSS outperforms the
      peak VO(2) in risk stratification for CHF in the presence of an ICD and/or CRT.
      Furthermore, a peak VO(2) <= 10 ml/kg/min rather than the traditional cutoff
      value <= 14 ml/min/kg may be more useful for risk stratification in the device
      era.

PMID- 21093300
TI  - Transcriptional signatures in donor lungs from donation after cardiac death vs
      after brain death: a functional pathway analysis.
AB  - BACKGROUND: Lung donation after cardiac death (DCD), in contrast to donation
      after brain death (DBD), is a promising and increasingly common method to help
      relieve the shortage of donor organs. We aimed to study the differential gene
      expression profiles in lungs of DCD and DBD patients and interpreted the
      differences using functional pathway analysis. METHODS: We performed microarray
      studies on pre- and post-transplant lung tissues from 7 DCD and 12 matched DBD
      patients. Gene profiling was performed by Affymetrix human gene U-133 plus 2
      GeneChip on 35 lung tissues. Principal Component Analysis (PCA), Significance
      Analysis of Microarray (SAM) and Hierarchical Clustering were performed to
      identify gross gene expression features and the lists of significantly regulated
      genes. We used Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis
      (IPA) to determine functional significance and the genomic network relationship.
      RESULTS: Gene expression profiles between DCD and DBD demonstrated a clear
      distinction by PCA, especially in the pre-transplant period. The gene sets
      enriched in DBD mapped to innate immunity, intracellular signaling, cytokine
      interaction, cell communication and apoptosis pathways. The networks produced by
      IPA showed that pro-inflammatory nodes played major role in pre-transplant DBD
      networks. However, the number of differentially regulated transcripts or gene
      sets decreased markedly after transplantation between DBD and DCD. CONCLUSION:
      Analysis of gene expression profiles in donor lungs showed significant
      differences in pathway activation between DBD and DCD lungs. The observation of
      fewer inflammatory features of DCD donor lungs suggests safe application of lung
      transplantation in properly preserved DCD donor lungs.

PMID- 21093301
TI  - Distinguishing three levels in explicit self-awareness.
AB  - This paper focuses on the development of explicit self-awareness in children.
      Mirror self-recognition has been the most popular paradigm used to assess this
      ability in children. Nevertheless, according to Rochat (2003), there are, at
      least, three different levels of explicit self-awareness. We therefore designed
      three different self-recognition tasks, each corresponding to one of these levels
      (a mirror self-recognition task, a picture self-recognition task and a masked
      self-recognition task). We observed a decrease in performance across the three
      tasks. This supports a developmental scale in self-awareness. Besides, the masked
      self-recognition performance makes it possible to assess the final and the most
      sophisticated level of self-awareness, i.e. the external self. To our best
      knowledge, this task is the first attempt to evaluate the external self in
      preverbal children. Our results indicate that 22-month old children show
      awareness of their external self or, at least, that this ability is in the
      process of being acquired.

PMID- 21093302
TI  - The ease of lying.
AB  - Brain imaging studies suggest that truth telling constitutes the default of the
      human brain and that lying involves intentional suppression of the predominant
      truth response. By manipulating the truth proportion in the Sheffield lie test,
      we investigated whether the dominance of the truth response is malleable. Results
      showed that frequent truth telling made lying more difficult, and that frequent
      lying made lying easier. These results implicate that (1) the accuracy of lie
      detection tests may be improved by increasing the dominance of the truth response
      and that (2) habitual lying makes the lie response more dominant.

PMID- 21093304
TI  - What do people with epilepsy know about their condition? Evaluation of a
      subspecialty clinic population.
AB  - Knowledge and understanding of chronic disease has an important role to play in
      establishing good quality outcomes. A small number of studies have looked at a
      number of different aspects of patient knowledge and self-management strategies.
      This study used three previously published scales to assess for the first time
      both the patients' personal knowledge of their own condition and their fund of
      knowledge about epilepsy in general, its treatment and consequences. The subjects
      were all patients attending a specialist-led epilepsy service in a tertiary care
      teaching hospital in Dublin, Ireland. Fifty-two subjects successfully completed
      three knowledge-based surveys focusing on personal information and compliance,
      safety, driving and employment legalities. Patients were more knowledgeable about
      the particulars of their individual condition rather than about epilepsy in
      general. Anti-epileptic drug compliance scores were highest overall; safety and
      legal issues ranked lowest. Many patients with epilepsy are not well informed
      about their disorder. Thus, there is a need for educational intervention in this
      population in order to optimize self-management strategies.

PMID- 21093305
TI  - Has disability discrimination legislation changed the legal framework for
      epilepsy in the United Kingdom?
AB  - In this paper, I review the way in which the legislative framework in the United
      Kingdom has defined epilepsy. Key legislative milestones in the last 100 years,
      and their implications for epilepsy, are discussed; as are some landmark legal
      rulings. The implications of the UK Disability Discrimination Act 1995 for people
      with epilepsy and barriers to the Act's effectiveness are considered, as are the
      evidence of its impact and difficulties in measuring the impact of the Act for
      people with epilepsy. I end with consideration of the possible implications for
      people with epilepsy of the new UK Equality Act.

PMID- 21093306
TI  - Epilepsy stigma: moving from a global problem to a global solution.

PMID- 21093307
TI  - Managing my treatment.

PMID- 21093308
TI  - What needs to change for people with epilepsy?

PMID- 21093309
TI  - Introduction: tracing the recent history of the 'falling sickness'.

PMID- 21093310
TI  - Fluctuating and constant valproate administration gives equivalent seizure
      control in rats with genetic and acquired epilepsy.
AB  - PURPOSE: Controlled-release formulations of Valproate (VPA) reduce side effects
      by minimizing peak plasma VPA concentrations in patients with epilepsy. However,
      the impact of this on anti-seizure efficacy has not been thoroughly explored.
      Here the pharmacokinetics and pharmacodynamics of chronic intermittent
      (consequently, peak VPA concentrations) and continuous VPA administration were
      directly compared in two rat models of epilepsy. METHODS: Genetic Absence
      Epilepsy Rats from Strasbourg (GAERS) received a single acute bolus of VPA (100
      mg/kg intravenously) combined with electroencephalography (EEG) and/or blood
      sampling for 180 min post-injection. GAERS and epileptic rats post-kainic acid
      induced status epilepticus were chronically infused intravenously (3-5 days,
      respectively) with (i) saline followed by in random order (ii) intermittent and
      (iii) continuous VPA (42 mg/kg/h), separated by two days of wash-out. Seizures
      were quantified using video-EEG monitoring and VPA levels measured in brain,
      cerebrospinal fluid and plasma. RESULTS: Following acute VPA administration
      seizure suppression in GAERS persisted after plasma VPA levels became very low.
      Chronic intermittent and continuous VPA significantly suppressed seizures in both
      models (p<0.01) with no difference between administration regimens. In GAERS, the
      pattern of seizure suppression during intermittent treatment was constant, in
      contrast to the fluctuating VPA plasma and brain levels. There was discordance
      between the temporal pattern of plasma, brain VPA levels and seizure suppression
      efficacy in GAERS. CONCLUSION: Administration regimes that result in fluctuating
      VPA blood levels achieve equivalent sustained seizure suppression as those that
      maintain steady mid-range concentrations.

PMID- 21093311
TI  - Epilepsy Action diamond jubilee. Conclusions.

PMID- 21093312
TI  - Living two lives.

PMID- 21093313
TI  - Diverse perspectives on developments in epilepsy surgery.
AB  - The objective of this article is to review the dramatic changes that have
      occurred in the field of epilepsy surgery since the founding of Epilepsy Action
      in 1950. We have chosen to consider these advances from the biomedical
      perspective (the physician and basic scientist), and the behavioral perspective
      (the psychologist and the patient). Both these viewpoints are equally important
      in understanding the evolution of epilepsy surgery over the past 60 years, but
      may not always be well synchronized.

PMID- 21093314
TI  - Validation of the Caprini risk assessment model in plastic and reconstructive
      surgery patients.
AB  - BACKGROUND: The Venous Thromboembolism Prevention Study (VTEPS) Network is a
      consortium of 5 tertiary referral centers established to examine venous
      thromboembolism (VTE) in plastic surgery patients. We report our midterm analyses
      of the study's control group to evaluate the incidence of VTE in patients who
      receive no chemoprophylaxis, and validate the Caprini Risk Assessment Model (RAM)
      in plastic surgery patients. STUDY DESIGN: Medical record review was performed at
      VTEPS centers for all eligible plastic surgery patients between March 2006 and
      June 2009. Inclusion criteria were Caprini score >=3, surgery under general
      anesthesia, and postoperative hospital admission. Patients who received
      chemoprophylaxis were excluded. Dependent variables included symptomatic deep
      vein thrombosis (DVT) or pulmonary embolism (PE) within the first 60
      postoperative days and time to DVT or PE. RESULTS: We identified 1,126 historic
      control patients. The overall VTE incidence was 1.69%. Approximately 1 in 9
      (11.3%) patients with Caprini score >8 had a VTE event. Patients with Caprini
      score >8 were significantly more likely to develop VTE when compared with
      patients with Caprini score of 3 to 4 (odds ratio [OR] 20.9, p < 0.001), 5 to 6
      (OR 9.9, p < 0.001), or 7 to 8 (OR 4.6, p = 0.015). Among patients with Caprini
      score 7 to 8 or Caprini score >8, VTE risk was not limited to the immediate
      postoperative period (postoperative days 1-14). In these high-risk patients, more
      than 50% of VTE events were diagnosed in the late (days 15-60) postoperative
      period. CONCLUSIONS: The Caprini RAM effectively risk-stratifies plastic and
      reconstructive surgery patients for VTE risk. Among patients with Caprini score
      >8, 11.3% have a postoperative VTE when chemoprophylaxis is not provided. In
      higher risk patients, there was no evidence that VTE risk is limited to the
      immediate postoperative period.

PMID- 21093315
TI  - Endothelial heparan sulfate controls chemokine presentation in recruitment of
      lymphocytes and dendritic cells to lymph nodes.
AB  - Heparan sulfate can bind several adhesion molecules involved in lymphocyte
      trafficking. However, the in vivo function of endothelial heparan sulfate in
      lymphocyte homing and stimulation of the immune response has not been elucidated.
      Here, we generated mutant mice deficient in the enzyme Ext1, which is required
      for heparan sulfate synthesis, in a Tek-dependent and inducible manner. Chemokine
      presentation was diminished in the mutant mice, causing the lack of appropriate
      integrin-mediated adhesion, and resulted in a marked decrease in lymphocyte
      sticking to high endothelial venules and in recruitment of resident dendritic
      cells through lymphatic vessels to the lymph nodes. As a consequence, mutant mice
      displayed a severe impairment in lymphocyte homing and a compromised contact
      hypersensitivity response. By contrast, lymphocyte rolling was increased because
      of loss of electrostatic repulsion by heparan sulfate. These results demonstrate
      critical roles of endothelial heparan sulfate in immune surveillance and immune
      response generation.

PMID- 21093316
TI  - Cell-cell propagation of NF-kappaB transcription factor and MAP kinase activation
      amplifies innate immunity against bacterial infection.
AB  - The enteroinvasive bacterium Shigella flexneri uses multiple secreted effector
      proteins to downregulate interleukin-8 (IL-8) expression in infected epithelial
      cells. Yet, massive IL-8 secretion is observed in Shigellosis. Here we report a
      host mechanism of cell-cell communication that circumvents the effector proteins
      and strongly amplifies IL-8 expression during bacterial infection. By monitoring
      proinflammatory signals at the single-cell level, we found that the activation of
      the transcription factor NF-kappaB and the MAP kinases JNK, ERK, and p38 rapidly
      propagated from infected to uninfected adjacent cells, leading to IL-8 production
      by uninfected bystander cells. Bystander IL-8 production was also observed during
      Listeria monocytogenes and Salmonella typhimurium infection. This response could
      be triggered by recognition of peptidoglycan and is mediated by gap junctions.
      Thus, we have identified a mechanism of cell-cell communication that amplifies
      innate immunity against bacterial infection by rapidly spreading proinflammatory
      signals via gap junctions to yet uninfected cells.

PMID- 21093317
TI  - Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity
      during Salmonella typhimurium infection.
AB  - The myeloid differentiation primary response gene 88 (Myd88) is critical for
      protection against pathogens. However, we demonstrate here that MyD88 expression
      in B cells inhibits resistance of mice to Salmonella typhimurium infection.
      Selective deficiency of Myd88 in B cells improved control of bacterial
      replication and prolonged survival of the infected mice. The B cell-mediated
      suppressive pathway was even more striking after secondary challenge. Upon
      vaccination, mice lacking Myd88 in B cells became completely resistant against
      this otherwise lethal infection, whereas control mice were only partially
      protected. Analysis of immune defenses revealed that MyD88 signaling in B cells
      suppressed three crucial arms of protective immunity: neutrophils, natural killer
      cells, and inflammatory T cells. We further show that interleukin-10 is an
      essential mediator of these inhibitory functions of B cells. Collectively, our
      data identify a role for MyD88 and B cells in regulation of cellular mechanisms
      of protective immunity during infection.

PMID- 21093318
TI  - Regulated expression of nuclear receptor RORgammat confers distinct functional
      fates to NK cell receptor-expressing RORgammat(+) innate lymphocytes.
AB  - Whether the recently identified innate lymphocyte population coexpressing natural
      killer cell receptors (NKRs) and the nuclear receptor RORgammat is part of the NK
      or lymphoid tissue inducer (LTi) cell lineage remains unclear. By using adoptive
      transfer of genetically tagged LTi-like cells, we demonstrate that NKR
      RORgammat(+) innate lymphocytes but not NK cells were direct progenitors to
      NKR(+)RORgammat(+) cells in vivo. Genetic lineage tracing revealed that the
      differentiation of LTi-like cells was characterized by the stable upregulation of
      NKRs and a progressive loss of RORgammat expression. Whereas interleukin-7 (IL-7)
      and intestinal microbiota stabilized RORgammat expression within such NKR-LTi
      cells, IL-12 and IL-15 accelerated RORgammat loss. RORgammat(+) NKR-LTi cells
      produced IL-22, whereas RORgammat- NKR-LTi cells released IFN-gamma and were
      potent inducers of colitis. Thus, the RORgammat gradient in NKR-LTi cells serves
      as a tunable rheostat for their functional program. Our data also define a
      previously unappreciated role of RORgammat- NKR-LTi cells for the onset or
      maintenance of inflammatory bowel diseases.

PMID- 21093319
TI  - Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin
      activation in innate-like B cells.
AB  - Marginal zone (MZ) B cells of the spleen and B1 cells, termed innate-like B
      cells, differ from follicular B cells by their attenuated Ca(2+) mobilization,
      fast antibody secretion, and increased cell adhesion. We identified and
      characterized Mzb1 as an endoplasmic reticulum-localized and B cell-specific
      protein that was most abundantly expressed in MZ B and B1 cells. Knockdown of
      Mzb1 in MZ B cells increased Ca(2+) mobilization and nuclear NFAT transcription
      factor localization, but reduced lipopolysaccharide-induced antibody secretion
      and integrin-mediated cell adhesion. Conversely, ectopic expression of an Lck
      Mzb1 transgene in peripheral T cells resulted in attenuated Ca(2+) mobilization
      and augmented integrin-mediated cell adhesion. In addition to its interaction
      with the substrate-specific chaperone Grp94, Mzb1 augmented the function of the
      oxidoreductase ERp57 in favoring the expression of integrins in their activated
      conformation. Thus, Mzb1 helps to diversify peripheral B cell functions by
      regulating Ca(2+) stores, antibody secretion, and integrin activation.

PMID- 21093320
TI  - MicroRNAs prevent the generation of autoreactive antibodies.
AB  - MicroRNAs have been shown to be critical for a number of aspects of immune system
      regulation and function. Here, we have examined the role of microRNAs in terminal
      B cell differentiation by analyzing Cd19-Cre(ki/+) Dicer1(fl/fl) mice. We found
      that in the absence of Dicer, the transitional and marginal zone (MZ) B cell
      compartments were overrepresented and follicular (FO) B cell generation was
      impaired. microRNA analysis revealed that miR185, a microRNA overexpressed in FO
      cells, dampened B cell receptor (BCR) signaling through Bruton tyrosine kinase
      downregulation. Dicer-deficient B cells had a skewed BCR repertoire with
      hallmarks of autoreactivity, which correlated with high titers of autoreactive
      antibodies in serum and autoimmune features in females. Together, our results
      reveal a crucial role for microRNAs in late B cell differentiation and in the
      establishment of B cell tolerance.

PMID- 21093321
TI  - STAT6 transcription factor is a facilitator of the nuclear receptor PPARgamma
      regulated gene expression in macrophages and dendritic cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a lipid-activated
      transcription factor regulating lipid metabolism and inflammatory response in
      macrophages and dendritic cells (DCs). These immune cells exposed to distinct
      inflammatory milieu show cell type specification as a result of altered gene
      expression. We demonstrate here a mechanism how inflammatory molecules modulate
      PPARgamma signaling in distinct subsets of cells. Proinflammatory molecules
      inhibited whereas interleukin-4 (IL-4) stimulated PPARgamma activity in
      macrophages and DCs. Furthermore, IL-4 signaling augmented PPARgamma activity
      through an interaction between PPARgamma and signal transducer and activators of
      transcription 6 (STAT6) on promoters of PPARgamma target genes, including FABP4.
      Thus, STAT6 acts as a facilitating factor for PPARgamma by promoting DNA binding
      and consequently increasing the number of regulated genes and the magnitude of
      responses. This interaction, underpinning cell type-specific responses,
      represents a unique way of controlling nuclear receptor signaling by inflammatory
      molecules in immune cells.

PMID- 21093323
TI  - Hes1 is a critical but context-dependent mediator of canonical Notch signaling in
      lymphocyte development and transformation.
AB  - Although canonical Notch signaling regulates multiple hematopoietic lineage
      decisions including T cell and marginal zone B cell fate specification, the
      downstream molecular mediators of Notch function are largely unknown. We showed
      here that conditional inactivation of Hes1, a well-characterized Notch target
      gene, in adult murine bone marrow (BM) cells severely impaired T cell development
      without affecting other Notch-dependent hematopoietic lineages such as marginal
      zone B cells. Competitive mixed BM chimeras, intrathymic transfer experiments,
      and in vitro culture of BM progenitors on Delta-like-expressing stromal cells
      further demonstrated that Hes1 is required for T cell lineage commitment, but
      dispensable for Notch-dependent thymocyte maturation through and beyond the beta
      selection checkpoint. Furthermore, our data strongly suggest that Hes1 is
      essential for the development and maintenance of Notch-induced T cell acute
      lymphoblastic leukemia. Collectively, our studies identify Hes1 as a critical but
      context-dependent mediator of canonical Notch signaling in the hematopoietic
      system.

PMID- 21093322
TI  - Alternative promoter usage at the Notch1 locus supports ligand-independent
      signaling in T cell development and leukemogenesis.
AB  - Loss of the transcription factor Ikaros is correlated with Notch receptor
      activation in T cell acute lymphoblastic leukemia (T-ALL). However, the mechanism
      remains unknown. We identified promoters in Notch1 that drove the expression of
      Notch1 proteins in the absence of a ligand. Ikaros bound to both canonical and
      alternative Notch1 promoters and its loss increased permissive chromatin,
      facilitating recruitment of transcription regulators. At early stages of
      leukemogenesis, increased basal expression from the canonical and 5'-alternative
      promoters initiated a feedback loop, augmenting Notch1 signaling. Ikaros also
      repressed intragenic promoters for ligand-independent Notch1 proteins that are
      cryptic in wild-type cells, poised in preleukemic cells, and active in leukemic
      cells. Only ligand-independent Notch1 isoforms were required for Ikaros-mediated
      leukemogenesis. Notch1 alternative-promoter usage was observed during T cell
      development and T-ALL progression. Thus, a network of epigenetic and
      transcriptional regulators controls conventional and unconventional Notch
      signaling during normal development and leukemogenesis.

PMID- 21093324
TI  - Effect of intravenous extracellular gadolinium based contrast medium on renal
      diffusion weighted images.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to compare precontrast and
      postcontrast renal diffusion-weighted images for signal intensity (SI), apparent
      diffusion coefficient (ADC), and lesion conspicuity. MATERIALS AND METHODS: In 62
      patients (mean age, 54 +/- 29; 29 men, 33 women) precontrast and postcontrast
      (0.1 mmol/kg of extracellular gadolinium-based contrast medium; mean, 3.3 +/- 0.9
      minutes], diffusion-weighted images at b values of 50 and 400 s/mm2 were compared
      (3 T). The SI, signal-to-noise ratio, and ADC of the renal cortex, medulla, and
      lesions were measured. Lesion contrast-to-noise ratios (against the medulla and
      cortex) were calculated. RESULTS: Postcontrast medullary SI decreased by 50% and
      cortical SI decreased by 33% and 39% on images at b = 50 s/mm2 and b = 400 s/mm2,
      respectively (P < .0001). The SI and signal-to-noise ratio of lesions did not
      change significantly after contrast, but lesion-medullary contrast-to-noise ratio
      was increased by 50% at both b = 50 s/mm2 and b = 400 s/mm2 (P < .005 and P =
      .0005, respectively) following contrast. Qualitative postcontrast lesion
      conspicuity was improved, with average scores of 2.8 +/- 0.9 for all lesions
      (kappa = 0.7 +/- 0.08) and 3.2 +/- 0.9 for solid lesions (kappa = 0.82 +/- 0.1).
      The ADC of renal cortex decreased (P = .03), but the ADC of renal medulla or
      renal lesions did not significantly change. CONCLUSION: Postcontrast diffusion
      weighted imaging causes a significant decrease in renal parenchymal signal
      without a significant change in lesion signal, resulting in increased lesion
      conspicuity.

PMID- 21093325
TI  - Where are the diagnostic codes in dentistry?

PMID- 21093326
TI  - Hb Stanleyville II [alpha 78(EF7) Asn->Lys] occurrence in combination with Hb
      Constant Spring.

PMID- 21093327
TI  - Kinetics of jump landing in agility dogs.
AB  - A recent survey reported an increased risk of injury in dogs participating in
      agility, a competitive canine sport involving different jumping activities. The
      aim of this study was to quantify the kinetic parameters during jump landing for
      commonly used obstacle types. It was hypothesised that with increasing obstacle
      height, the vertical force and vertical and accelerative horizontal impulse will
      increase as a result of a lengthened aerial phase, a more acute landing angle and
      the need to convert potential into forwards kinetic energy. Simultaneous kinetic
      and kinematic data were recorded from 11 competition agility dogs jumping over
      obstacle combinations of different height and inter-obstacle distance. Speed and
      landing angle of the second of the two consecutive jumps were successfully
      controlled by obstacle height and distance between obstacles. Statistical
      analysis showed differences between obstacles for peak vertical force, vertical
      impulse and accelerative horizontal impulse (increasing values with more acute
      landing angles). Extremely high peak vertical force was observed in the forelimbs
      (4.5 times bodyweight) when landing from a hurdle jump at high speed. Further
      detailed studies into the consequences for internal limb structures are warranted
      in order to clarify how this might be related to injury.

PMID- 21093328
TI  - Comparison of the epidemiology of epizootic haemorrhagic disease and bluetongue
      viruses in dairy cattle in Israel.
AB  - An outbreak of epizootic haemorrhagic disease virus (EHDV) in cattle in Israel in
      2006 enabled a comparison of the spatial distribution of epidemic exposure to
      EHDV with that of exposure to bluetongue virus (BTV), which is endemic in the
      country. The seroprevalence of both viruses was examined in 1650 serum samples
      collected from 139 farms representative of the spatial distribution of dairy
      cattle in Israel. A significant association between exposure to EHDV and BTV was
      demonstrated in both univariate and multivariate analyses. Recent exposure to BTV
      and EHDV (demonstrated by seroprevalence in calves) was clustered in different
      geographical locations, indicating that the two viruses had different patterns of
      spread, that of EHDV being influenced by winds and terrain barriers and that of
      BTV by herd immunity.

PMID- 21093329
TI  - IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial
      allodynia/hyperalgesia following a trigeminal nerve injury.
AB  - It has been reported that the whisker pad (WP) area, which is innervated by the
      second branch of the trigeminal nerve, shows allodynia/hyperalgesia following
      transection of the mental nerve (MN: the third branch of the trigeminal nerve).
      However, the mechanisms of this extra-territorial pain induction still remain
      unclear. Glia and cytokines are known to facilitate perception of noxious input,
      raising a possibility that these non-neuronal elements are involved in the
      induction and spread of allodynia/hyperalgesia at non-injured skin territory. One
      day after MN transection, tactile allodynia/hyperalgesia developed on the
      ipsilateral WP area, which is in the non-injured skin territory. The tactile
      allodynia/hyperalgesia lasted for more than 56 days. In response to MN
      transection, astrocytes and microglia appeared to be in an activated state, and
      interleukin (IL)-1beta was up-regulated in astrocytes in the trigeminal
      subnucleus caudalis (Vc). Allodynia/hyperalgesia at WP area induced by MN
      transection was attenuated dose-dependently by IL-1 receptor antagonist IL-1ra
      (i.t., 0.05, 0.5, and 5 pg/rat). Fos-like immunoreactive (Fos-Li) neurons were
      observed in the Vc after non-noxious mechanical stimulation of the WP area in the
      rats with MN transection. Administration of IL-1ra also attenuated the number of
      Fos-Li neurons dose-dependently. Administration of a noncompetitive antagonist of
      NMDA receptors MK-801 (i.t., 5 MUg/rat) reversed allodynia/hyperalgesia. IL-1
      receptor type I (IL-1RI) was localized in Fos- and phospho NR1-immunoreactive
      neurons. These results suggest that IL-1beta in the Vc plays an important role in
      the development of extra-territorial tactile allodynia/hyperalgesia after MN
      transection.

PMID- 21093330
TI  - Primary follicular lymphoma of the conjunctiva in a 6-year-old child.
AB  - Primary follicular lymphomas arise in the lymph nodes or spleen or in extranodal
      sites. Ocular adnexal tumors are rare. We report the case of a 6-year-old boy
      with a 3-mm conjunctival mass. The lesion was resected with clean surgical
      margins. The child has been closely monitored and has remained cancer free for 3
      years.

PMID- 21093331
TI  - Clinical spectrum of pediatric blepharokeratoconjunctivitis.
AB  - PURPOSE: To evaluate the incidence, symptoms, clinical signs, and therapy
      instituted in children with blepharokeratoconjunctivitis (BKC). METHODS: In this
      observational, retrospective case series, we reviewed all medical records of
      pediatric patients presenting to the ophthalmology clinic at the Kalawati Saran
      Children's Hospital, New Delhi, India from 2003 to 2006. History, clinical
      characteristics, and treatment protocol were noted, as well as reason for
      presentation/referral and subsequent diagnosis. RESULTS: Of 5,012 pediatric
      patients, 615 (12%) demonstrated features of BKC. Boys were more commonly
      affected (62%) than girls. The mean age at presentation was 6.7 years (range, 7
      months to 16 years). Lid involvement and conjunctival congestion were consistent
      features. Anterior (seborrheic variety) blepharitis was seen in nearly half the
      children (302), followed by chalazion (18%), external hordeolum (17%), ulcerative
      anterior blepharitis (6%), phlyctenular keratoconjunctivitis (6%), and marginal
      ulcerative keratitis (2%). Refractive error was evident in 521 of 615 children
      (85%) with BKC. All patients were treated with daily eyelid hygiene, warm
      compresses, and topical antibiotics. Corticosteroid drops were prescribed in 14%
      and oral erythromycin in 23%. CONCLUSIONS: BKC was the commonest diagnosis at
      consultation among all pediatric referrals. Anterior blepharitis was more common
      than posterior blepharitis. Severe cases with corneal involvement accounted for
      only 5% of the disease spectrum.

PMID- 21093332
TI  - The use of distance stereoacuity assessment in determining the effectiveness of
      minus lenses in intermittent exotropia.
AB  - PURPOSE: Minus lens treatment has been advocated for intermittent exotropia to
      prevent progression and has been found to be effective in improving the control
      of the deviation in the distance. However, the effectiveness of this treatment is
      difficult to ascertain because of the lack of standardized outcome measures.
      Distance stereoacuity has been reported to be a reliable assessment of control of
      intermittent exotropia. In this study, its role as an outcome measure in the
      efficacy of minus lens treatment was examined by the use of the Frisby-Davis
      Distance stereotest. METHODS: Patients (n = 24) with intermittent exotropia
      participated. Their distance stereoacuity was tested with the Frisby-Davis
      Distance stereotest at baseline and with varying minus lens powers (of -1, -2 and
      -3 D) that were tested randomly, as were the distance binocular visual acuity and
      angle of deviation. RESULTS: Varying minus lens powers had a significant effect
      on the angle of deviation and binocular visual acuity but not distance
      stereoacuity. However, both measures of binocularity, distance stereoacuity, and
      binocular visual acuity tended to diminish with the stronger minus lens power of 
      3 D. Participants actually demonstrated difficulty in accommodating through the
      stronger lenses. CONCLUSIONS: Distance stereoacuity (and binocular visual acuity)
      cannot reliably be used to determine the optimum minus lens strength that could
      be used in these patients to reduce the angle of deviation and regain
      binocularity in the distance. An additional observation was made that stronger
      lenses should perhaps be avoided to prevent binocular and visual discomfort.

PMID- 21093333
TI  - Comparison of UK and US screening criteria for detection of retinopathy of
      prematurity in a developing nation.
AB  - PURPOSE: To determine the incidence, risk factors, and appropriateness of
      differing guidelines in developed nations for screening for retinopathy of
      prematurity (ROP) in a single nursery in a large urban city in southern Turkey.
      METHODS: The records of 260 premature infants born <=34 weeks in a single
      tertiary unit were retrospectively reviewed for ROP risk factors and diagnosis.
      Applicability of UK and US criteria were assessed by the use of receiver
      operating characteristic curves. RESULTS: ROP of any stage was present in 60
      infants (23%); ROP requiring treatment was seen in 30 (11.5%). Univariate
      analysis showed a significant relationship among the following factors:
      gestational age, birth weight, total duration of supplemental oxygen, duration of
      mechanical ventilation, respiratory distress syndrome, anemia, and
      intraventricular hemorrhage (p < 0.0001). Multiple logistic regression analysis
      showed gestational age (p = 0.039), birth weight (p = 0.05), respiratory distress
      syndrome (p = 0.05), and anemia (p = 0.004) as independent predictors of ROP
      requiring treatment. Area under curve for gestational age alone for diagnosing
      stage 2 or greater ROP was 0.824 +/- 0.03 (p = 0.0001) and for birth weight alone
      was 0.808 +/- 0.03 (p = 0.0001). UK screening criteria detected all stage 2 and
      greater ROP; US screening criteria missed 2 infants with stage 2 ROP but detected
      all treatment-requiring disease. Adoption of these screening criteria would have
      reduced unnecessary examinations by either 21% (UK) or 37% (US). CONCLUSIONS: UK
      and US criteria improved the detection accuracy for ROP requiring treatment in
      Turkey and should be studied for other developing nations.

PMID- 21093334
TI  - The benefit of long-term growth hormone (GH) replacement therapy in hypopituitary
      adults with GH deficiency: results of the German KIMS database.
AB  - OBJECTIVE: To evaluate the treatment effects of long-term growth hormone (GH)
      replacement therapy in adults with GH deficiency (GHD) who were followed in KIMS
      Germany (Pfizer International Metabolic Database), a national surveillance study.
      DESIGN: The analysis was performed using baseline and long-term data (range: 4-10
      years) of 440 consecutively documented patients (216 women and 224 men) with GHD,
      aged 20 to 49 years, enrolled in KIMS Germany. Serum insulin-like growth factor I
      (IGF-I), fasting blood glucose, fasting serum total cholesterol and low-density
      lipoprotein cholesterol (LDL-C) as well as body mass index (BMI), waist
      circumference (WC) and hip circumference (HC) at baseline and at last visit were
      studied. Furthermore, QoL-AGHDA score was determined to assess quality-of-life
      (QoL). RESULTS: The mean dose of GH over all years was 0.41 mg per day in women
      and 0.37 mg per day in men. IGF-I and IGF-I SDS levels (standard deviation score)
      increased significantly (p<0.001) during GH treatment. The QoL-AGHDA score
      decreased significantly (p<0.001), indicating long-lasting improvement in QoL. In
      total cholesterol, LDL-C and fasting blood glucose, no significant changes were
      found. Only six patients developed type 2 diabetes during follow-up. Females and
      males similarly increased significantly in BMI, WC and HC. During GH treatment,
      recurrences of pituitary or central nervous system tumours or further de novo
      neoplasia were reported in 6 or 11 patients, respectively. The number of the most
      frequently reported GH treatment-associated adverse events was low. CONCLUSION:
      These observational data show long-term beneficial effects of GH replacement
      therapy on QoL and show no significant effects on total cholesterol, LDL-C or
      BMI, WC and HC. Additionally, our data indicate that GH replacement therapy in
      adults is well tolerated.

PMID- 21093335
TI  - Fatal infantile lactic acidosis and a novel homozygous mutation in the SUCLG1
      gene: a mitochondrial DNA depletion disorder.
AB  - Mitochondrial DNA (mtDNA) depletion syndromes are autosomal recessive conditions
      in which the mtDNA copy number is greatly decreased in affected tissues. The
      encephalomyopathic group of these syndromes comprise mutations in SUCLA2 and
      SUCLG1 subunits [1]. In this report, we describe a patient with fatal infantile
      lactic acidosis associated with mutations in the SUCLG1 gene and mtDNA depletion.
      Histological and enzymatic abnormalities in skeletal muscle support the diagnosis
      of this recently described mitochondrial disorder. This case is unique in that
      prenatal imaging suggested the diagnosis and that the confirmatory molecular
      diagnosis was established at 2 weeks of age. We describe prenatal MRI and
      neonatal laboratory disturbances that can point the clinician toward
      consideration of this diagnosis when treating infantile lactic acidosis.

PMID- 21093336
TI  - Betaine-homocysteine methyltransferase: human liver genotype-phenotype
      correlation.
AB  - Betaine-homocysteine methyltransferase (BHMT) catalyzes the remethylation of
      homocysteine. BHMT is highly expressed in the human liver. In the liver, BHMT
      catalyzes up to 50% of homocysteine metabolism. Understanding the relationship
      between BHMT genetic polymorphisms and function might increase our understanding
      of the role of this reaction in homocysteine remethylation and in S
      adenosylmethionine-dependent methylation. To help achieve those goals, we
      measured levels of BHMT enzyme activity and immunoreactive protein in 268 human
      hepatic surgical biopsy samples from adult subjects as well as 73 fetal hepatic
      tissue samples obtained at different gestational ages. BHMT protein levels were
      correlated significantly (p<0.001) with levels of enzyme activity in both fetal
      and adult tissues, but both were decreased in fetal tissue when compared with
      levels in the adult hepatic biopsies. To determine possible genotype-phenotype
      correlations, 12 tag SNPs for BHMT and the closely related BHMT2 gene were
      selected from SNPs observed during our own gene resequencing studies as well as
      from HapMap. These SNPs data were used to genotype DNA from the adult hepatic
      surgical biopsy samples, and genotype-phenotype association analysis was
      performed. Three SNPs (rs41272270, rs16876512, and rs6875201), located 28kb
      upstream, in the 5'-UTR and in intron 1 of BHMT, respectively, were significantly
      correlated with both BHMT activity (p=3.41E-8, 2.55E-9 and 2.46E-10,
      respectively) and protein levels (p=5.78E-5, 1.08E-5 and 6.92E-6, respectively).
      We also imputed 230 additional SNPs across the BHMT and BHMT2 genes, identifying
      an additional imputed SNP, rs7700790, that was also highly associated with
      hepatic BHMT enzyme activity and protein. However, none of the 3 genotyped or one
      imputed SNPs displayed a "shift" during electrophoretic mobility shift assays.
      These observations may help us to understand individual variation in the
      regulation of BHMT in the human liver and its possible relationship to variation
      in methylation.

PMID- 21093337
TI  - Electronically assisted prescription will minimise drug transcription errors.
AB  - OBJECTIVE: To assess the impact of administration errors when transcribing
      treatments to nurses' administration forms, and to estimate the impact of
      electronically assisted prescription (EAP) in minimising these errors. METHOD: A
      prospective, observational study in hospitalised patients. In a representative
      sample changes in treatment in the 24 h before the examination are analysed.
      Transcription errors were detected when checking the discrepancies between the
      medical prescription and the nurses' treatment administration forms. Error
      incidence was calculated as a whole and by ward, type of error, administration
      route and their potential danger. The possible reduction in new errors per day if
      the EAP were to be introduced in all units was estimated. RESULTS: Of the 416
      prescriptions recorded, the overall percentage of transcription errors was 12.4%,
      9.8% in medical units and 15.2% in surgical units. Most of the errors were made
      when a new medicine was added (29.4%) and the frequency of administration was
      changed (27.4%). With regard to their gravity, 98% did not harm the patients, and
      57.7% were filed as "Category C". Taking into account that 1 change of treatment
      is made per patient per day, the introduction of the EAP is predicted to prevent
      64 new errors daily in the hospital. CONCLUSIONS: There are so many transcription
      errors that they should be taken into account when designing strategies to
      improve care quality. EAP is an efficient tool to eliminate errors associated
      with the transcription of prescriptions.

PMID- 21093338
TI  - Role of CYP450 in pharmacokinetics and pharmacogenetics of antihypertensive
      drugs.
AB  - INTRODUCTION: Antihypertensive drugs are principally metabolised by enzymes of
      the P450 (CYP450) cytochrome family. Response to hypertensive treatment whose
      genetic basis is beginning to be known presents inter-individual differences
      among patients. OBJECTIVE: The aim of this review is to document the role of
      cytochrome enzymes P450 in the metabolising process of antihypertensive drugs,
      and to identify the most relevant polymorphisms in genes that code for these
      enzymes in order to facilitate future studies in hypertension pharmacogenetics.
      METHODS: A keyword search was performed in the following literature databases:
      Pubmed, Rxlist and Medscape. Genetic polymorphism public databases were also
      consulted (PharmGKB, NCBI and the CYP450 allele nomenclature committee web page.
      RESULTS: Enzymes CYP2D6, CYP2C9, CYP2D19 and CYP3A4 participate in the
      metabolising process of most antihypertensive drugs. Considering the allelic
      frequency in the population and the variability in the clinical response
      associated with genetic polymorphism, we find the study of the following alleles
      CYP2D6 *2, *4, deletion and duplication; CYP2C9*2 and *3, CYP2C19 *2 and
      CYP3A4*1B to be of crucial importance. CONCLUSIONS: The study of polymorphisms in
      P450 cytochrome genes may contribute to an individualised therapy in the
      treatment against hypertension.

PMID- 21093339
TI  - [Review of the stabitlity of photosensitive medications].
AB  - OBJECTIVES: Identify the photosensitive drugs included in the hospital
      pharmacotherapeutic guide and search for stability data on the storage,
      reconstitution, and dilution of these compounds. METHODS: The data were obtained
      by referencing technical specifications, information provided by drug
      laboratories, and in some cases, we performed a more extensive bibliographic
      search (tertiary sources and conference lectures) for each particular medication.
      We also performed a data search on the PubMed information database (from 2004 to
      2009). The drugs were placed in alphabetical order by brand since the stability
      of each drug when exposed to light does not depend exclusively on the primary
      active ingredient. Eight columns describe the principal characteristics of the
      drugs: brand name, active ingredient, laboratory, storage, reconstitution and
      dilution conditions, observations, and references. RESULTS: The listing was
      comprised of 139 photosensitive medicines, of the 1,954 included in the
      pharmacotherapeutical guide (table 1). CONCLUSIONS: The lack of studies published
      on the stability of photosensitive medications provided the need for an internal
      review at our hospital. It is important for drug-producing laboratories to
      perform photo-sensitivity tests on their products, with the results presented in
      the technical specifications in order to provide more accessible and reliable
      information. We believe that this should be required by law.

PMID- 21093340
TI  - Escherichia coli septic arthritis of a lumbar facet joint following urinary tract
      infection.
AB  - Septic arthritis of a lumbar facet joint is a rare condition. We report the case
      of a 77-year-old diabetic woman who developed fever and back pain 15 days after
      she had been diagnosed with a genitourinary infection for which she had received
      ciprofloxacin. Physical examination showed fever (38 degrees C) and pain on
      pressure over the lower lumbar spinous vertebral apophyses and over the lower
      left paraspinal musculature. Investigations showed a white cell count of
      8.4*109/l, neutrophils 85.3%, erythrocyte sedimentation rate of 125 mm/h, and C
      reactive protein of >=9 mg/dl. Two blood cultures were both positive for
      Escherichia coli resistant to ciprofloxacin. There was no growth of pathogens
      from the urine cultures. Scintigraphy with gallium citrate Ga67 showed vertical
      lower lumbar (L4-L5) radionuclide uptake lateralized to the left. Magnetic
      resonance imaging of the lumbar spine demonstrated signal changes and alteration
      of the structure at the left interapophyseal L4-L5 joint, an adjacent small
      collection of 1cm in diameter, and infiltration of the surrounding soft tissues,
      which extended to the epidural area, left conjunction hole, and paraspinal
      muscles. The patient was treated with intravenous cefotaxime and gentamicin and
      bed rest for 21 days, and recovered. This is the first report of interapophyseal
      arthritis caused by E. coli.

PMID- 21093341
TI  - Maxillary osteomyelitis by mucormycosis: report of four cases.
AB  - Mucormycosis is a fungal infection commonly affecting structures in the head and
      neck, such as the air sinuses, orbits, and the brain. Common predisposing factors
      include diabetes mellitus and immunosuppression. We describe our clinical
      experience with four cases of mucormycosis of the maxillary antrum associated
      with uncontrolled diabetes mellitus managed at our centre. Early diagnosis and
      prompt treatment can significantly reduce the mortality and morbidity of this
      lethal fungal infection.

PMID- 21093342
TI  - Immunogenicity and reactogenicity of a combined fully liquid DTPw-HepB-Hib
      pentavalent vaccine in healthy infants: no clinically relevant impact of a birth
      dose of hepatitis B vaccine.
AB  - OBJECTIVES: In this open-label, non-randomized phase II study, the safety and
      immunogenicity of a fully liquid diphtheria-tetanus-whole cell pertussis
      hepatitis B-Haemophilus influenzae type b (DTPw-HepB-Hib) combination vaccine
      (Quinvaxem((r))) were assessed in infants who had or had not received a birth
      dose of hepatitis B (HepB) vaccine. STUDY DESIGN: Two groups of infants, 'HepB at
      birth' (n=110) and 'no HepB at birth' (n=108), were enrolled and received a
      primary vaccination course using a 2-4-6 months schedule. RESULTS:
      Seroprotection/seroconversion rates of >95% were achieved against all antigens
      included in the combination vaccine for both study groups. Although significantly
      higher anti-hepatitis B virus (p<0.001) and anti-tetanus (p=0.031) antibody
      titers were achieved in group 'HepB at birth' when compared with group 'no HepB
      at birth', the proportion of 'no HepB at birth' subjects achieving protective
      titers was non-inferior to the proportion of subjects in group 'HepB at birth'.
      The birth dose of HepB vaccine did not seem to influence the safety pattern of
      the DTPw-HepB-Hib combination vaccine. CONCLUSIONS: The present study
      demonstrated that the fully liquid DTPw-HepB-Hib vaccine was safe and immunogenic
      when administered using a 2-4-6 months immunization schedule, regardless of
      whether or not infants had received a dose of HepB vaccine at birth.

PMID- 21093343
TI  - Work related characteristics of back and neck pain among employees of a Swiss
      University Hospital.
AB  - OBJECTIVES: 1) To explore the staff- and work-related risk factors for spinal
      pain among hospital employees, 2) to investigate the effect of staff- and work
      related variables on the consequences of spinal pain, such as doctor visits and
      sick leave. METHODS: A mailed survey was carried out in a random sample of 2700
      employees stratified for occupational categories (administration staff, nurses,
      nurse assistants, physicians, support staff and allied health professionals). The
      questionnaire measured self-reported spinal pain, consequences of pain, and work
      characteristics. RESULTS: The response rate was 48.1% (1298/2700). The one-year
      prevalence of spinal pain was 67.3%, highest among nurses (75.6%) and lowest
      among support staff (54.9%). Reported work characteristics associated with spinal
      pain included frequent work at a poorly adapted work station (odds ratio (OR)
      1.90 [1.24-2.93]) and having to maintain a position for a long time (OR 1.71
      [1.25-2.34]). No significant correlations were observed with lifting, patient
      handling, material handling, or working on nightshift. Sickness leave due to
      spinal pain was significantly associated with duration of pain episode (OR 4.08
      for>3 months compared to less than 10 days), and with work categories (OR 2.58
      for nurse assistants compared to nurses). CONCLUSION: In this population of
      hospital employees, being a nurse, working at a poorly adapted work place, and
      having to maintain positions for a long time were related independently to spinal
      pain. Nurse assistants had a higher risk of work absenteeism.

PMID- 21093345
TI  - [Vascularized bone grafting from the volar distal radius for carpal bones
      reconstruction].
AB  - We report the use of vascularized bone graft harvested from the volar aspect of
      distal radius for carpal bone reconstruction. This transplant is known and used
      since 1965, but the technical description of reliable harvesting more recent is
      presented. The anatomical dissection of 30 corpses found in a constant way the
      presence of the transverse carpal artery which born from radial artery. This
      vascularized bone graft was used for the treatment of 112 scaphoid nonunion with
      an average follow-up of 27.82 months (10-107). Union was obtained in 95.54% of
      the cases with an average of 6.7 weeks (6-9). We report also the result of this
      vascularized bone graft for the revascularization of the lunatum in 22 patients
      with Kienbock's disease with an average follow-up of 74 months (60-124). The
      postoperative MRI control with a minimum of 8 months showed 17 healing, three
      stabilizations of lesions and two failures requiring a secondary palliative
      surgery. The use of a vascularized transplant harvested from the volar aspect of
      distal radius is now a well codified, meticulous but reliable and sure technique,
      which requires a single approach for the reconstruction of some carpal bones
      (scaphoid, lunatum) allowing a locoregional anesthesia and an outpatient basis.

PMID- 21093346
TI  - [Pollicization of the most radial finger in five-fingered hand: report of three
      cases].
AB  - The treatment objective in the five-finger hand is to create an opposable thumb
      with two phalanges and a first web space having a normal appearance. We report
      three cases of pollicization of the most radial finger in two patients evaluated
      by the Percival Score. Currently, the treatment of reference of five-finger hand
      is the pollicization of the most radial finger. We present a particular technical
      enhancement, which is the adaptation to a shorter osseous skeleton and the
      utilization of extrinsic or intrinsic motors present in the radial side of the
      hand.

PMID- 21093347
TI  - [Pedicled bone transfers for digit reconstruction].
AB  - The techniques of pedicled bone transfer harvested from the forearm and the hand
      are largely used in digit reconstruction during the last three decades. Comparing
      with the vascularized bone-free transfer techniques, their realization is
      generally easier because of the single operative field and the absence of
      microvascular suture. Based on their clinical experience, the authors try to make
      the point about the surgical techniques and the indications of the principal
      pedicled bone transfers harvested from the forearm and the hand for digit
      reconstruction.

PMID- 21093348
TI  - Material characterization of ex vivo prostate tissue via spherical indentation in
      the clinic.
AB  - BACKGROUND: The mechanical characterization of prostate tissue has not received
      much attention and is often disconnected from the clinic, where samples are
      readily attained. METHODS: We developed a spherical indenter for the clinic to
      generate force-displacement data from ex vivo prostate tissue. Indentation
      velocity, depth, and sphere diameter, and four means of estimating elastic
      modulus (EM) were validated. EM was then estimated for 26 prostate specimens
      obtained via prostatectomy and 6 samples obtained from autopsy. Prostatectomy
      prostates were evaluated clinically upon digital rectal exam and pathologically
      post-extirpation. FINDINGS: Whole-mount measurements yielded median EM of 43.2
      kPa (SD=59.8 kPa). Once sliced into cross-sections, median EM for stage T2 and T3
      glands were 30.9 and 71.0 kPa, respectively, but not significantly different.
      Furthermore, we compared within-organ EM difference for prostates with
      (median=46.5 kPa, SD=22.2 kPa) and without (median=31.0 kPa, SD=63.1 kPa)
      palpable abnormalities. INTERPRETATION: This work finds that diseased prostate
      tissue is stiffer than normal tissue, stiffness increases with disease severity,
      and large variability exists between samples, even though disease differences
      within a prostate are detectable. A further study of late-stage cancers would
      help to strengthen the findings presented in this work.

PMID- 21093349
TI  - A modified low-cost haptic interface as a tool for complex tactile stimulation.
AB  - This study describes the development and evaluation of a platform for the
      investigation of the human tactile ability. Specifically, it enables precise and
      reproducible application of time-varying 3D force stimuli to the skin of an
      immobilized human limb. We proceeded in the following steps: (1) programming a
      low-cost haptic interface to apply time-varying 3D force stimuli to a fixed rigid
      target, (2) implementing a combined feed-forward/feedback controller to improve
      the platform's precision and reliability in force stimulation, (3) determining
      the optimal tuning of the control loop parameters and (4) evaluating the system's
      performances when applying time-varying 3D force stimuli to an immobilized human
      finger pad. The system's performances were evaluated in terms of the accuracy and
      repeatability when delivering standard 3D force stimuli, i.e., stimuli with
      specified force components in the normal and skin tangential directions. Within
      the range of forces tested (5 N in various directions), the maximum difference
      between the actual force and the desired value during static phases was <30 mN
      (accuracy) and the root-mean-square of the standard deviation (repeatability) was
      15 mN during static phases and <75 mN during dynamic phases.

PMID- 21093350
TI  - A temporal sampling framework for developmental dyslexia.
AB  - Neural coding by brain oscillations is a major focus in neuroscience, with
      important implications for dyslexia research. Here, I argue that an oscillatory
      'temporal sampling' framework enables diverse data from developmental dyslexia to
      be drawn into an integrated theoretical framework. The core deficit in dyslexia
      is phonological. Temporal sampling of speech by neuroelectric oscillations that
      encode incoming information at different frequencies could explain the perceptual
      and phonological difficulties with syllables, rhymes and phonemes found in
      individuals with dyslexia. A conceptual framework based on oscillations that
      entrain to sensory input also has implications for other sensory theories of
      dyslexia, offering opportunities for integrating a diverse and confusing
      experimental literature.

PMID- 21093351
TI  - Combining functional genomics and chemical biology to identify targets of
      bioactive compounds.
AB  - Genome sequencing projects have revealed thousands of suspected genes,
      challenging researchers to develop efficient large-scale functional analysis
      methodologies. Determining the function of a gene product generally requires a
      means to alter its function. Genetically tractable model organisms have been
      widely exploited for the isolation and characterization of activating and
      inactivating mutations in genes encoding proteins of interest. Chemical genetics
      represents a complementary approach involving the use of small molecules capable
      of either inactivating or activating their targets. Saccharomyces cerevisiae has
      been an important test bed for the development and application of chemical
      genomic assays aimed at identifying targets and modes of action of known and
      uncharacterized compounds. Here we review yeast chemical genomic assays
      strategies for drug target identification.

PMID- 21093352
TI  - Optical tweezers for the micromanipulation of plant cytoplasm and organelles.
AB  - Laser trapping of micron-sized particles can be achieved utilizing the radiation
      pressure generated by a focused infrared laser beam. Thus, it is theoretically
      possible to trap and manipulate organelles within the cytoplasm and remodel the
      architecture of the cytoplasm and membrane systems. Here we describe recent
      progress, using this under utilized technology, in the manipulation of
      cytoplasmic strands and organelles in plant cells.

PMID- 21093353
TI  - Rare earth-doped lead borate glasses and transparent glass-ceramics: structure
      property relationship.
AB  - Correlation between structure and optical properties of rare earth ions in lead
      borate glasses and glass-ceramics was evidenced by X-ray-diffraction, Raman, FT
      IR and luminescence spectroscopy. The rare earths were limited to Eu(3+) and
      Er(3+) ions. The observed BO(3)<->BO(4) conversion strongly depends on the
      relative PbO/B(2)O(3) ratios in glass composition, giving important contribution
      to the luminescence intensities associated to (5)D(0)-(7)F(2) and (5)D(0)-(7)F(1)
      transitions of Eu(3+). The near-infrared luminescence and up-conversion spectra
      for Er(3+) ions in lead borate glasses before and after heat treatment were
      measured. The more intense and narrowing luminescence lines suggest partial
      incorporation of Er(3+) ions into the orthorhombic PbF(2) crystalline phase,
      which was identified using X-ray diffraction analysis.

PMID- 21093354
TI  - Spectroscopic studies on the interaction of cilostazole with iodine and 2,3
      dichloro-5,6-dicyanobenzoquinone.
AB  - The electron accepting properties of the 2,3-dichloro-5,6-dicyanobenzoquinone and
      iodine and electron donating properties of the drug cilostazole have been studied
      using the UV-vis, FT-IR, GC-MS and Far-IR techniques. The interaction of
      cilostazole drug with iodine and 2,3-dichloro-5,6-dicyanobenzoquinone resulted
      via the initial formation of charge-transfer complex as an intermediate. The rate
      of formation of the product have been measured and discussed as a function of
      solvent and temperature. The complexes have been found by Job's method of
      continuous variation revealed that the stoichiometry of the complexes in both the
      cases was 1:1. The enthalpies and entropies of formation of the complexes have
      been obtained by determining their rate constant at three different temperature.
      The ionization potential of the donor was determined using the charge-transfer
      absorption bands of the complexes and the same was found comparable with that
      computed using MOPAC PM3 method.

PMID- 21093355
TI  - Detection of pneumonia using free-text radiology reports in the BioSense system.
AB  - OBJECTIVE: Near real-time disease detection using electronic data sources is a
      public health priority. Detecting pneumonia is particularly important because it
      is the manifesting disease of several bioterrorism agents as well as a
      complication of influenza, including avian and novel H1N1 strains. Text radiology
      reports are available earlier than physician diagnoses and so could be integral
      to rapid detection of pneumonia. We performed a pilot study to determine which
      keywords present in text radiology reports are most highly associated with
      pneumonia diagnosis. DESIGN: Electronic radiology text reports from 11 hospitals
      from February 1, 2006 through December 31, 2007 were used. We created a
      computerized algorithm that searched for selected keywords ("airspace disease",
      "consolidation", "density", "infiltrate", "opacity", and "pneumonia"),
      differentiated between clinical history and radiographic findings, and accounted
      for negations and double negations; this algorithm was tested on a sample of 350
      radiology reports. We used the algorithm to study 189,246 chest radiographs,
      searching for the keywords and determining their association with a final
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) diagnosis of pneumonia. MEASUREMENTS: Performance of the search
      algorithm in finding keywords, and association of the keywords with a pneumonia
      diagnosis. RESULTS: In the sample of 350 radiographs, the search algorithm was
      highly successful in identifying the selected keywords (sensitivity 98.5%,
      specificity 100%). Analysis of the 189,246 radiographs showed that the keyword
      "pneumonia" was the strongest predictor of an ICD-9-CM diagnosis of pneumonia
      (adjusted odds ratio 11.8) while "density" was the weakest (adjusted odds ratio
      1.5). In general, the most highly associated keyword present in the report,
      regardless of whether a less highly associated keyword was also present, was the
      best predictor of a diagnosis of pneumonia. CONCLUSION: Empirical methods may
      assist in finding radiology report keywords that are most highly predictive of a
      pneumonia diagnosis.

PMID- 21093356
TI  - Persistence of varicella-zoster virus viraemia in patients with herpes zoster.
AB  - BACKGROUND: Herpes zoster is caused by the reactivation of varicella-zoster virus
      from sensory neurons. The commonest complication following zoster is chronic pain
      termed post herpetic neuralgia. OBJECTIVES: To investigate the dynamics of VZV
      viraemia and viral load following the resolution of zoster and its relationship
      to PHN development. STUDY DESIGN: Blood samples were collected at baseline, 1
      month, 3 months and 6 month from a prospective study of 63 patients with active
      zoster. Quantification of VZV DNA in whole blood was performed using a real-time
      PCR assay. RESULTS: During acute zoster, all patients had detectable VZV DNA in
      their blood. VZV DNA remained detectable in the blood of 91% of patients at 6
      months although levels declined significantly (p<0.0001). A history of prodromal
      symptoms (p=0.005) and severity of pain at baseline (p=0.038) as well as taking
      antivirals (p=0.046) and being immunocompromised (p=0.043) were associated, with
      longer time to recovery from PHN. Viral DNA loads were consistently higher in
      patients with risk factors for PHN and higher viral DNA loads over time were
      associated with longer time to recovery (p=0.058 overall and 0.038 in
      immunocompetent). CONCLUSIONS: Based on these observations we hypothesise that
      VZV replication persists following acute shingles and that higher viral DNA loads
      contribute to the risk factors for PHN.

PMID- 21093357
TI  - Spike-wave discharges in WAG/Rij rats are preceded by delta and theta precursor
      activity in cortex and thalamus.
AB  - OBJECTIVE: In order to unravel the mechanisms underlying the "sudden" onset of
      spontaneous absences in genetically prone subjects, we investigated the immediate
      precursors of spike-wave discharges (SWDs) produced in cortico-thalamo-cortical
      neuronal networks. METHODS: A time-frequency analysis of the cortical and
      thalamic ECoG of WAG/Rij rats was accomplished with a continuous wavelet
      decomposition of SWDs, 3 s prior to the onset of SWDs (pre-SWD), and in control
      periods devoid of SWDs. RESULTS: The pre-SWD ECoG consisted of delta and theta
      components in 80-90% of all SWDs simultaneously in cortex and thalamus, the co
      occurrence of delta and theta was rare (7%) during control periods. The
      occurrence of delta and theta events in pre-SWDs in the cortex preceded that in
      the thalamus. The frequency of theta component in cortex correlated positively
      with that in thalamus, this correlation was less strong for delta. CONCLUSION:
      Precursors of SWDs comprise of delta and theta, their co-occurrence is typical
      for non-epileptic periods. Thalamic and cortical theta are strongly related.
      Rhythmic precursors appear earlier in cortex than in thalamus, and this is in
      line with the cortical origin of SWD. SIGNIFICANCE: Simultaneous presence of
      delta and theta events in EEG is a condition for the occurrence of SWDs.

PMID- 21093358
TI  - Phase brings a new phase to the exploration of the elusive neonatal EEG.

PMID- 21093359
TI  - Fat tissue alters quadriceps response to femoral nerve magnetic stimulation.
AB  - OBJECTIVE: We investigate the influence that inguinal fat has on maximal
      quadriceps response to femoral nerve magnetic stimulation. METHODS: Vastus
      lateralis M-wave amplitude and quadriceps twitch peak torque were measured (i) in
      lean and overweight subjects and (ii) when slices of pig fat ranging from 2 to 18
      mm in thickness were placed between the coil and the nerve. RESULTS: In
      overweight group, the maximal response could not be elicited when intensity was
      <=90% and <=85% of maximal power for twitch torque and M-wave amplitude,
      respectively. The maximal response was obtained at 80% of maximal power in the
      lean group. Negative correlations between relative twitch torque changes and
      inguinal thickness were observed. Fat thickness altered quadriceps response at 14
      mm and 8 mm in the lean and overweight groups, respectively. CONCLUSIONS: The
      capacity of femoral nerve magnetic stimulation to deliver supramaximal
      stimulation is altered when fat thickness below the coil increases. SIGNIFICANCE:
      Special caution should be taken by clinicians when overweight or obese subjects
      are tested using femoral nerve magnetic stimulation.

PMID- 21093360
TI  - Ocular vestibular evoked myogenic potentials are abnormal in internuclear
      ophthalmoplegia.
AB  - OBJECTIVE: The cervical vestibular evoked myogenic potential (cVEMP) is sensitive
      to lower brainstem lesions affecting the vestibulo-collic pathway. We wished to
      determine whether the ocular VEMP (oVEMP), a recently-described otolith-ocular
      reflex, is also abnormal in patients with brainstem lesions. We tested patients
      with internuclear ophthalmoplegia (INO), caused by a brainstem lesion in the
      medial longitudinal fasciculus (MLF), to investigate whether the oVEMP is
      abnormal in patients with a lesion of the otolith-ocular pathway. METHODS: We
      describe a patient who developed a right INO during his first episode of
      demyelination, and report results from 12 additional patients, most of whom had
      multiple sclerosis. All subjects were stimulated with air-conducted tone bursts.
      cVEMPs and oVEMPs were measured using surface electrodes placed over the neck and
      beneath the eyes. RESULTS: Overall, oVEMPs showed significantly more
      abnormalities (69%) than cVEMPs (8%). Ocular VEMPs were absent with stimulation
      of 13/26 ears, significantly delayed in 5/26 cases and normal in only 8/26 cases.
      CONCLUSION: Ocular VEMPs are often abnormal in patients with multiple sclerosis
      who have an INO, while cVEMPs are usually normal. SIGNIFICANCE: Ocular VEMPs
      provide a new, non-invasive method for examining central vestibular pathways in
      humans and are sensitive to lesions of the MLF.

PMID- 21093361
TI  - Prevalence of different parasomnias in the general population.
AB  - OBJECTIVE: To estimate lifetime and current prevalence (defined as having
      experienced the specific parasomnia at least once during the last 3 months) of
      different parasomnias in the general population. In addition, to study the
      relationship between the different parasomnias and gender, depressive mood, and
      symptoms of sleep apnea, insomnia and restless legs, as well as estimating the
      prevalence of having multiple parasomnias. METHODS: Population based cross
      sectional study. One thousand randomly selected adults (51% female), 18years and
      above, participated in a telephone interview in Norway. RESULTS: Lifetime
      prevalence of the different parasomnias varied from about 4% to 67%. For sleep
      walking lifetime prevalence was 22.4% and current prevalence 1.7%. For the other
      parasomnias, lifetime and current prevalence were as follows: sleep talking 66.8%
      and 17.7%, confusional arousal 18.5% and 6.9%, sleep terror 10.4% and 2.7%,
      injured yourself during sleep 4.3% and 0.9%, injured somebody else during sleep
      3.8% and 0.4%, sexual acts during sleep 7.1% and 2.7%, nightmare 66.2% and 19.4%,
      dream enactment 15.0% and 5.0%, sleep related groaning 31.3% and 13.5%, and sleep
      related eating 4.5% and 2.2%. Depressive mood was associated with confusional
      arousal, sleep terror, sleep-related injury, and nightmare. There were few
      associations between the parasomnias and gender and symptoms of sleep apnea,
      insomnia, and restless legs, respectively. About 12% reported having five or more
      parasomnias. CONCLUSIONS: This is one of few population based studies
      investigating the prevalence of parasomnias. Several parasomnias were highly
      prevalent in the general population. The data need to be interpreted with caution
      due to methodological issues, i.e., low response rate and single questions.

PMID- 21093362
TI  - Prevalence of insomnia and sleep characteristics in the general population of
      Spain.
AB  - OBJECTIVE: The goals of this study were to estimate the prevalence of insomnia
      symptomatology and diagnoses in the Spanish general population and to determine
      if certain sleep parameters were related to specific insomnia symptoms. METHODS:
      This is a cross-sectional telephone survey performed in the general population of
      Spain using a representative sample of 4065 individuals aged 15years or older.
      The participation rate was 87.5%. Interviews were conducted using the Sleep-EVAL
      system. The questions were related to sociodemographic characteristics, sleep
      wake schedule, events occurring during sleep, insomnia symptoms, daytime
      consequences and DSM-IV diagnoses of sleep disorders. RESULTS: Overall, 20.8%
      (95% C.I. 19.6-22.1%) of the sample reported at least one insomnia symptom
      occurring at least three nights/week. The prevalence was higher in women than in
      men (23.9% vs. 17.6%) and increased with age. Difficulty maintaining sleep at
      least three nights/week was the most prevalent symptom. DSM-IV insomnia disorder
      diagnoses were found in 6.4% (95% C.I. 5.6-7.1%) of the sample. Delayed bedtime
      and wake-up time, irregular bedtime hours and hypnagogic hallucinations were the
      most frequent in participants who had difficulty initiating sleep. Perception of
      light and "too short" sleep were the most frequent in participants who had early
      morning awakenings. Participants who had a non-restorative sleep were more likely
      to extend sleep on days off than other insomnia participants. Medical
      consultations in the previous year were more frequent in insomnia participants
      compared to participants without insomnia. One-fifth of insomnia participants
      were using sleep-promoting medication. CONCLUSIONS: Insomnia is frequent in
      Spain, affecting up to one in five individuals. Results show that insomnia is
      multidimensional and needs to be assessed as such.

PMID- 21093363
TI  - Characteristics of insomnia in a primary care setting: EQUINOX survey of 5293
      insomniacs from 10 countries.
AB  - OBJECTIVE: To describe the characteristics of insomnia in primary care
      physicians' (PCPs') practices in 10 countries and to understand how the
      difficulty of maintaining sleep (DMS) was or was not associated with other
      insomnia symptoms such as difficulty initiating sleep (DIS), early morning
      awakenings (EMA) or nonrestorative sleep (NRS) in PCPs patients with insomnia.
      METHODS: International, noninterventional, cross-sectional, observational survey
      conducted in a primary care setting in subjects complaining of sleep disturbances
      in 10 countries. A questionnaire based on DSM-IV and ICSD criteria was
      administered. RESULTS: Thirteen thousand one hundred twenty-four subjects were
      enrolled by 647 physicians; 5293 of them (32.6%) had insomnia and were surveyed.
      The population was predominantly female (63.9%) with a mean age of 47.8+/-15.3
      years; 39.9% of these patients have already been treated for sleep difficulties.
      Combination of all types of insomnia symptoms (DIS+DMS+EMA+NRS) was the most
      frequently reported combination (38.6% of the subjects), while the percentage of
      subjects presenting with only one type of insomnia symptom (DIS, DMS, EMA or NRS)
      was very low: 3%, 1.8%, 0.9% and 1.4% respectively. DMS was on average the most
      commonly reported insomnia symptom (80.2%). Multiple logistic regression showed
      that DMS, EMA and NRS symptoms were significantly linked with each other and also
      to other insomnia criteria (sleep satisfaction, sleep quality, sleep duration,
      number of hours of sleep, frequency of insomnia symptoms, wake up rested /
      unrested and non restorative sleep). CONCLUSIONS: Patients visiting PCPs with
      insomnia are likely to present with severe and poly-symptomatic insomnia.

PMID- 21093364
TI  - Periodic limb movements in sleep exhibit a circadian rhythm that is maximal in
      the late evening/early night.
AB  - OBJECTIVE: Periodic limb movements in sleep (PLMS) show a time-of-night pattern,
      with most movements at the beginning of the night. Our study aimed to determine
      whether this pattern is due to an endogenous circadian rhythm, like that in the
      related movement disorder Restless Legs Syndrome (RLS). METHODS: Four healthy
      older adults with a screening PLMI>20 were studied in an inpatient forced
      desynchrony protocol with an imposed sleep-wake cycle of 20 h for 12 "nights,"
      allowing separation of circadian and sleep homeostatic influences on leg
      movements. We recorded sleep polysomnographically throughout each scheduled
      episode, including left and right anterior tibialis EMG. RESULTS: PLMS in Stage 2
      showed both a significant time-within-sleep pattern and a significant circadian
      rhythm. The circadian rhythm in PLMS peaked at the circadian phases when usual
      sleep onset occurs, preceding the evening rise in melatonin secretion.
      CONCLUSIONS: In our subjects, the circadian pattern of PLMs expression was very
      similar to that previously reported in patients with RLS. This evidence for a
      circadian rhythm in PLMS has implications for treatment and provides direction
      for future studies of the pathophysiology of this movement disorder.

PMID- 21093365
TI  - Associations of nonrestorative sleep with insomnia, depression, and daytime
      function.
AB  - STUDY OBJECTIVES: Nonrestorative sleep (NRS) complaints are common but
      associations with insomnia, daytime function or depressive symptoms are not well
      established. This study aims to (1) describe insomnia related symptoms and sleep
      quality in those with NRS compared to those with no NRS; (2) identify the
      independent associations between NRS, insomnia severity, and depression; and (3)
      identify the association between NRS and daytime function independent of insomnia
      severity and depression. DESIGN: Cross sectional survey of enrollees at a health
      plan in the Midwestern United States. MEASUREMENT: Respondents were surveyed
      about the presence and frequency of NRS complaints, depression, insomnia severity
      and related symptoms. Multivariate regression was used to examine the study's
      three research aims. PARTICIPANTS: Study sample consisted of 541 subjects with
      NRS and 717 who reported never experiencing any NRS symptoms. RESULTS: We found a
      statistically significant interaction between NRS and total sleep duration such
      that the association between sleep duration and sleep quality was attenuated in
      those with NRS compared to those without NRS (b=-0.26, SE=0.07, p<0.0001). In
      multivariate analysis, subthreshold, moderate and severe insomnia were associated
      with NRS (OR [95%CI]=5.93 [4.24-8.31], 9.22 [6.15-13.83] and 6.10 [3.34-11.14],
      respectively). NRS was independently associated with daytime physical function,
      cognitive function and emotional function OR [95%CI]=2.21 [1.59-3.08], 1.90 [1.37
      2.64] and 1.71 [1.23-2.36], respectively. CONCLUSION: NRS is a complex concept
      that should be further defined and studied in the larger context of sleep
      quality, other insomnia related symptoms, daytime function and depression.

PMID- 21093366
TI  - Heavy metals (lead, cadmium and mercury) in maternal, cord blood and placenta of
      healthy women.
AB  - Lead, cadmium and mercury were measured in placental tissue, umbilical cord and
      maternal blood samples of 1578 women who delivered at the Al-Kharj King Khalid
      Hospital between 2005 and 2006. The aim of this study was to evaluate the status
      of heavy metal exposure in mothers and their newborns and to identify predictors
      of maternal exposure. Lead was detected in all cord and maternal blood and in 96%
      of placental tissues. Only in 0.89% and 0.83% of cord and maternal blood samples
      were the levels of lead above the CDC threshold limit of 10 MUg/dl. Maternal
      blood lead was also higher (2.3%) than the German Reference value in women of 7
      MUg/dl. Approximately 9.3% of women had a placental lead above the 95th
      percentile in the range of 0.83-78 MUg/g dry wt., a level of possible
      developmental toxicity. Cadmium was detected in 94.8% and 97.9% of cord and
      maternal blood samples respectively, though only five newborns had a cadmium
      level above the OSHA threshold limit of 5 MUg/l. Comparing our results to the
      newly revised German Reference value for nonsmokers, 48.6% of mothers had blood
      cadmium levels >1.0 MUg/l. We found as well that 25% of women had placental
      cadmium in the >75th percentile, in the range of 0.048-4.36 MUg/g dry wt., which
      is likely to affect fetal growth and development. Of the maternal and cord blood
      samples, 11.2% and 13%, respectively, had mercury levels >5.8 MUg/l, which is the
      EPA reference dose. Nearly 49% of women had mercury levels >2.0 MUg/l, the German
      Reference value for those who consume fish <=3 times a month. Around 50% of the
      mothers had placental mercury in the range of 0.031-13.0 MUg/g dry wt. Regression
      analyses indicated that the levels of metals in the blood and placenta were
      influenced by several factors. This study provides informative baseline
      biomonitoring data and reveals a substantial exposure to heavy metals in non
      occupationally exposed Saudi mothers and their newborns that might jeopardize the
      health of both. Additional research is also urgently needed to explore factors
      such as environment, diet, lifestyle and/or cultural habits contributing to
      maternal and fetal exposures. Preventive measures to eliminate or minimize the
      unnecessary risk of fetus exposure to heavy metals or other pollutants during
      pregnancy should be initiated once these factors are identified.

PMID- 21093367
TI  - Heart rate biofeedback fails to enhance children's ability to identify time spent
      in moderate to vigorous physical activity.
AB  - Physical activity recommendations for children in several countries advise that
      all young people should accumulate at least 60 min of moderate to vigorous
      physical activity every day. Perceiving physical activity intensity, however, can
      be a difficult task for children and it is not clear whether children can
      identify their levels of moderate to vigorous physical activity in accordance
      with the recommended guidelines. This study aimed to (1) explore whether children
      can identify time spent in moderate to vigorous physical activity; and (2)
      investigate whether heart rate biofeedback would improve children's ability to
      estimate time spent in moderate to vigorous physical activity. Thirty seven
      children (15 boys and 22 girls, mean age 12.6 years) wore data recording Polar
      E600 heart rate monitors during eight physical education lessons. At the end of
      each lesson children's estimated time in zone was compared to their actual time
      in zone. During a six lesson Intervention phase, one class was assigned to a
      biofeedback group whilst the other class acted as the control group and received
      no heart rate biofeedback. Post-Intervention, students in the biofeedback group
      were no better than the control group at estimating time spent in zone (mean
      relative error of estimation biofeedback group: Pre-Intervention 41+/-32% to Post
      Intervention 28+/-26%; control group: Pre-Intervention 40+/-39% to Post
      Intervention 31+/-37%). Thus it seems that identifying time spent in moderate to
      vigorous physical activity remains a complex task for children aged 11-13 even
      with the help of heart rate biofeedback.

PMID- 21093368
TI  - A simple method for cardioplegia administration and suture control using foley
      catheter during ascending aorta replacement and aortic root surgery.
AB  - There is no standardised approach for cardioplegia administration during
      ascending aorta replacement (AAR) and the techniques used so far are quite
      variable and show important limitations. In order to overcome these limitations,
      we propose a simple and inexpensive technique using a Foley catheter for
      cardioplegia administration and bleeding control in case of AAR or aortic root
      surgery. The benefits of our technique are the technical simplicity and the low
      cost that makes this approach an ideal solution for cardioplegia administration
      in all cases of AAR.

PMID- 21093369
TI  - Additional financial costs borne by cancer patients: a narrative review.
AB  - PURPOSE: To review out-of-pocket costs related to cancer that are borne by
      patients and their families. METHODS: A literature search using key terms
      relating to out-of-pocket costs incurred by cancer patients and their families
      was undertaken to generate a comprehensive narrative synthesis of the information
      available. RESULTS: Four themes were identified: measuring costs; sources of
      costs; the impact of costs and reducing costs. The wide variety of measures for
      ascertaining hidden costs makes comparison of findings difficult; some articles
      cover a very narrow range of costs. Qualitative research is useful for
      elucidating a wide range of costs. Costs pertaining to hospital visits, nutrition
      and clothing are widely mentioned. Low additional expenditure may indicate that
      needs/wants are going unmet. Financial capacity to cope and subjective perception
      of impact are important. Low income, younger age, chemotherapy and living rurally
      are associated with greater impact. Extra expense can exert long-term effects on
      family finances. Primary care follow-up, telemedicine and treatments that entail
      fewer visits may serve to reduce patient costs. CONCLUSIONS: The key question is
      how to organise/deliver cancer care in order to reduce additional expenses to
      patients and families. Future research could identify critical time-points and
      demographic groups susceptible to significant additional costs, in order to
      target support at those most in need.

PMID- 21093370
TI  - Pain in cancer patients: the Greek experience.
AB  - PURPOSE OF THE RESEARCH: Pain is not only one of the most undesirable side
      effects of cancer but also one of its major complications. This study attempted
      to evaluate and describe the pain characteristics and pain control in patients
      with advanced cancer and to identify factors related to effective analgesic
      treatment. METHODS AND SAMPLE: A descriptive cross-sectional study involving the
      eight larger oncology centres in Greece was conducted in 2008. Cancer patients (n
      = 134) attending the oncology outpatient departments were interviewed using a 35
      item questionnaire regarding pain- and treatment-related characteristics. KEY
      RESULTS: The great majority of the patients (72%) with advanced malignancy
      reported high pain intensity and 66.4% experienced the pain as continuous.
      Although most patients (81%) responded to treatment, more than 30% reported side
      effects and asked for treatment to change. Better informed patients about the
      disease showed higher response to pain treatment (OR 3.21; 95%CI 1.28-8.01).
      Adherence to treatment was related to pain response (OR 3.05; 95%CI 1.06-8.75),
      whereas negative attitudes and feelings toward treatment were related with
      reluctance to take analgesic treatment (OR 4.27; 95%CI 1.31-13.89). Patients'
      request for changing medication was significantly related to the presence of side
      effects (OR 8.26; 95%CI 2.80-24.42) and pain response to treatment (OR 0.09;
      95%CI 0.03-0.31). CONCLUSIONS: Negative attitudes and feelings toward treatment
      combined with deficits in patient education/information seem to influence both
      pain response and therapy compliance suggesting the need for more comprehensive
      approach to pain management of cancer patients.

PMID- 21093371
TI  - Piloting electronic self report symptom assessment - Cancer (ESRA-C) in Hong
      Kong: a mixed method approach.
AB  - PURPOSE: The benefits of utilizing computerized assessment in clinical settings
      have been reported in studies over the last three decades and more recently in
      the oncology settings. This study aimed to assess the feasibility and
      acceptability of using an electronic self report symptom assessment tool among
      Chinese oncology patients. METHODS AND SAMPLE: The tool, developed by The
      University of Washington, Distributed Health Assessment and Intervention Research
      (DHAIR) group was translated into Chinese. The adapted web-based survey platform,
      the Electronic Self Report Assessment - Cancer (ESRA-C), was tested in a local
      cancer resource center in Hong Kong. Participants' perceptions of the
      acceptability and feasibility of the symptom assessment process were assessed
      using the Acceptability E-scale as well as observation and qualitative interview
      data. Demographic data were also collected through the touch screen computer
      system. A convenience sample of 30 (11 male and 19 female) oncology patients was
      recruited to use the touch-screen computer to assess participants' symptoms using
      ESRA-C. RESULTS: The acceptability scale indicated moderately high acceptability
      in each subscale (mean score of 3.32-4.71). On average, participants took 17.5
      min (SD: 8.9) to complete the ESRA-C. The qualitative interview data revealed
      that the majority (25 participants) asserted that the ESRA-C was useful and
      effective in reporting personal health conditions. CONCLUSIONS: The study
      suggested that electronic assessment can offer a feasible, attractive, and viable
      means of implementing regular and comprehensive symptom assessment, which can
      lead to better symptom management in cancer patients.

PMID- 21093373
TI  - Push or pull? Relationships between lung cancer patients' perceptions of quality
      of care and use of complementary and alternative medicine.
AB  - Little is known about relationships between quality of care (QoC) and use of
      complementary and alternative medicine (CAM) among patients with lung cancer
      (LC). PURPOSE: This study examines CAM-use among patients with LC in Sweden,
      associations between QoC and CAM-use among these patients, and reported aspects
      of LC-care perceived as particularly positive and negative by patients, as well
      as suggestions for improving QoC. METHODS: Survey data from 94 patient members of
      the Swedish LC patient organization about CAM-use and QoC as measured by the
      instrument "Quality from the patient's perspective" were analyzed. RESULTS: Fifty
      (53%) LC-patients used CAM, with 40 of the CAM-users reporting that CAM helped
      them. The most common CAMs used were dietary supplements and natural remedies,
      followed by prayer. Significantly more patients reported using prayer and
      meditation for cure than was the case for other types of CAM used. Less than half
      the CAM-users reported having spoken with staff from the biomedical health care
      system about their CAM-use. Patients provided numerous suggestions for improving
      LC-care in a variety of areas, aiming at a more effective and cohesive care
      trajectory. No differences in QoC were found between CAM-users and non-CAM-users,
      but differences in CAM-use i.e. type of CAM, reasons for using CAM, and CAM
      provider consulted could be associated with different experiences of care.
      CONCLUSIONS: It is important to recognize that CAM-users are not a homogeneous
      group but might seek different types of CAMs and CAM-providers in different
      situations depending on experiences of care.

PMID- 21093372
TI  - A comparison of disrupted sleep patterns in women with cancer-related fatigue and
      postmenopausal women without cancer.
AB  - PURPOSE: Fatigue and disrupted sleep often coexist and both are prominent
      clinical problems in cancer affecting quality of life. Disrupted sleep patterns
      are likely related to cancer-related fatigue. The relationship needs further
      investigation. This study aimed to characterize and compare disrupted sleep
      patterns in fatigued breast cancer patients receiving chemotherapy with
      postmenopausal women without a history of cancer. Anxiety levels were also
      examined. METHODS: Data for this secondary analysis came from two studies. Global
      sleep quality and state anxiety were self-reported by 30 fatigued female breast
      cancer chemotherapy outpatients and 32 non-cancer postmenopausal women using
      Pittsburgh Sleep Quality Index (PSQI) and State-Trait Anxiety Inventory,
      respectively. RESULTS: Fatigued breast cancer patients showed significant sleep
      difficulties, characterized by prolonged sleep onset latency (M=54.3, SD=49.2
      min) and frequent nighttime awakenings, despite 40% of the patients using sleep
      medications three or more times a week. Compared to the non-cancer comparison
      group, fatigued patients reported significantly longer sleep latency (p=0.041),
      more use of sleep medications (p=0.006), and higher total PSQI scores (p=0.005).
      State anxiety levels did not differ between the two groups (p=0.88). CONCLUSIONS:
      Sleep is disrupted in fatigued breast cancer women undergoing chemotherapy.
      Nearly all fatigued patients (97%) had trouble sleeping (global PSQI scores>5),
      indicating significant difficulties in overall sleep quality among those
      patients. Knowledge of the nature of sleep disruption among cancer patients may
      contribute to CRF symptom management leading to tailored interventions designed
      to improve sleep quality in cancer patients thereby managing fatigue and
      improving quality of life.

PMID- 21093375
TI  - Care for people with an intellectual impairment or mental health problems: moving
      forwards.

PMID- 21093376
TI  - Interprofessional mentoring: enhancing students' clinical learning.
AB  - Interprofessional (IP) collaboration is recognized as critical for patient
      centred care. The clinical setting is an ideal environment for students to learn
      the competencies required to effectively work with providers from other
      professions. To enhance traditional clinical placements, we propose an IP
      mentoring approach, defined as learning that takes place between providers and
      students who are from different disciplines or health professions. In IP
      mentoring, students have primary relationships with their preceptors, but also
      have interactions with providers from other professions. We implemented IP
      mentoring with the support of two faculties of nursing in Alberta, Canada who
      provided an IP clinical focus for interested fourth year students. We emphasized
      to providers and students that there are no prescribed interactions that comprise
      IP mentoring; experiences between providers and students are context-specific and
      often informal. Through our evaluation we demonstrated that in IP mentoring,
      provider commitment was important, students engaged in IP activities of varying
      complexity, and students learned about roles of other professions and how to work
      together to provide patient-centred care. IP mentoring is an effective learning
      strategy to enhance students' knowledge and skills in IP collaboration without
      radical changes to the structure of the placements or to the educational
      curricula.

PMID- 21093377
TI  - A review of the management of pulmonary arterial hypertension associated with
      congenital heart disease.
AB  - Approximately 5-10% of adolescent and adult patients with congenital heart
      disease (CHD) will develop pulmonary arterial hypertension (PAH). Patients with
      PAH associated with CHD (PAH-CHD) exhibit several similarities to those with
      idiopathic and other associated forms of PAH, especially with regards to their
      non-specific, cardinal symptoms. The development of PAH-CHD can lead to lifelong
      impairment although, paradoxically, survival may be better versus idiopathic PAH.
      Patients with PAH-CHD may experience social limitations, and emotional and
      psychological issues, arising from their disease burden. Nurses and other allied
      healthcare professionals are well placed to deliver the individually-tailored
      care that patients with PAH-CHD require. Activities known to be of particular
      benefit include patient engagement and education, patient empowerment, colleague
      training, and ensuring effective communication across the multidisciplinary team.
      Recent developments in the management of PAH-CHD have led to changes in the
      medical needs and optimal care of this patient population. This review aims to
      provide an overview of the natural course, diagnosis, symptoms and impact of PAH
      CHD. We also aim to communicate the current standards in management of patients
      with PAH-CHD, and how their outlook can be improved in the future.

PMID- 21093374
TI  - Mammographic surveillance in women younger than 50 years who have a family
      history of breast cancer: tumour characteristics and projected effect on
      mortality in the prospective, single-arm, FH01 study.
AB  - BACKGROUND: Evidence supports a reduction in mortality from breast cancer with
      mammographic screening in the general population of women aged 40-49 years, but
      the effect of family history is not clear. We aimed to establish whether
      screening affects the disease stage and projected mortality of women younger than
      50 years who have a clinically significant family history of breast cancer.
      METHODS: In the single-arm FH01 study, women at intermediate familial risk who
      were younger than 50 years were enrolled from 76 centres in the UK, and received
      yearly mammography. Women with BRCA mutations were not explicitly excluded, but
      would be rare in this group. To compare the FH01 cohort with women not receiving
      screening, two external comparison groups were used: the control group of the UK
      Age Trial (106,971 women aged 40-42 years at recruitment, from the general
      population [ie, average risk], followed up for 10 years), and a Dutch study of
      women with a family history of breast cancer (cancer cases aged 25-77 years,
      diagnosed 1980-2004). Study endpoints were size, node status, and histological
      grade of invasive tumours, and estimated mortality calculated from the Nottingham
      prognostic index (NPI) score, and adjusted for differences in underlying risk
      between the FH01 cohort and the control group of the UK Age Trial. This study is
      registered with the National Research Register, number N0484114809. FINDINGS:
      6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received
      yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009;
      surveillance and reporting of cancers is still underway. 136 women were diagnosed
      with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the
      interval between screening events, and three (2%) symptomatically after failing
      to attend their latest mammogram. Invasive tumours in the FH01 study were
      significantly smaller (p=0.0094), less likely to be node positive (p=0.0083), and
      of more favourable grade (p=0.0072) than were those in the control group of the
      UK Age Trial, and were significantly less likely to be node positive than were
      tumours in the Dutch study (p=0.012). Mean NPI score was significantly lower in
      the FH01 cohort than in the control group of the UK Age Trial (p=0.00079) or the
      Dutch study (p<0.0001). After adjustment for underlying risk, predicted 10-year
      mortality was significantly lower in the FH01 cohort (1.10%) than in the control
      group of the UK Age Trial (1.38%), with relative risk of 0.80 (95% CI 0.66-0.96;
      p=0.022). INTERPRETATION: Yearly mammography in women with a medium familial risk
      of breast cancer is likely to be effective in prevention of deaths from breast
      cancer.

PMID- 21093378
TI  - A novel technique of stenting for laparoscopic pyeloplasty in children.
AB  - PURPOSE: We introduce the novel technique of a percutaneous pyelo-ureterostomy
      stent for laparoscopic pyeloplasty in children, which overcomes the limitations
      of previously described stenting techniques. MATERIALS AND METHODS: A Chiba
      needle is passed percutaneously across the anterior wall of the renal pelvis
      after completion of the anterior pyelo-ureteric anastamotic line. A guide wire is
      inserted through the trocar followed by an angiocatheter over the wire. The stent
      is passed through the angiocatheter, over the wire and across the wall of the
      renal pelvis. The wire is withdrawn and the stent distal tip is advanced to the
      mid-ureter. The posterior anastamotic line is then completed and the renal pelvis
      closed. The stent is capped on postoperative day 1 and removed in the office on
      postoperative day 10. RESULTS: Since 2007 we have used this approach for 14
      laparoscopic pyeloplasties (5 right, 9 left) in children with a mean age of 8.8
      years (range 5-17). Mean time of insertion was 9:55 min with no difficulties or
      perioperative complications noted. CONCLUSION: The antegrade pyelo-ureteral stent
      is easily and quickly inserted percutaneously as well as removed in the office,
      thus obviating the need for a second anesthetic.

PMID- 21093380
TI  - Lacosamide in the treatment of acute recurrent seizures and periodic epileptiform
      patterns in critically ill patients.
AB  - We investigated the safety, tolerability, and effectiveness of lacosamide (LCM)
      in patients with acute recurrent seizures or with periodic epileptiform activity
      captured during continuous EEG monitoring. A total of 17 patients received LCM;
      12 patients received LCM as a second or third antiepileptic drug (AED), one
      patient as a fourth AED, and one patient as a fifth AED. No additional AEDs were
      introduced after LCM in 15 patients. Twelve patients responded to LCM with
      improvement in the seizures or periodic epileptiform activity. Two patients
      required further AED management or burst suppression. No adverse effects,
      including symptomatic bradycardia and allergic reactions, were seen for
      intravenous infusion dosages up to 300 mg. Eleven patients were eventually
      discharged on LCM. LCM is an important new AED in the add-on treatment of acute
      recurrent seizures and periodic epileptiform activity in critically ill patients.

PMID- 21093379
TI  - Effect of vitamin E on oxidative stress in the contralateral testis of neonatal
      and pubertal hemicastrated rats.
AB  - OBJECTIVE: To evaluate whether the antioxidant vitamin E can prevent the harmful
      effects of reactive oxidative stress (ROS) that occur during compensatory
      testicular hypertrophy (CTH). MATERIALS AND METHODS: Thirty Sprague-Dawley rats
      were divided into six equal groups: neonatal hemicastrated vitamin E (NH_Vit
      E/NH) and sham surgical controls (NC), and pubertal hemicastrated vitamin E
      (PH_Vit E/PH) and sham surgical controls (PC). Vitamin E was administered orally
      to the NH_Vit E and PH_Vit E groups three times a week from week 3-12 prior to
      sacrifice. Antioxidant enzymes were measured in testis samples from each animal.
      RESULTS: Differences in superoxide dismutase activity were observed between the
      NH (21.04 +/- 0.48) and NH_Vit E (22.62 +/- 0.64) groups (P = 0.008); the PH
      (20.59 +/- 0.11) and PC (20.91 +/- 0.20) groups (P = 0.032); and the PH (20.59 +/
      0.11) and PH_Vit E (22.32 +/- 1.01) groups (P = 0.008). Thiobarbituric acid
      reactive substance in the PH and PH_Vit E groups was 0.097 +/- 0.022 and 0.036 +/
      0.004 (P = 0.008), respectively; and in the NH and NH_Vit E groups it was 0.135
      +/- 0.02 and 0.039 +/- 0.003 (P = 0.008), respectively. CONCLUSIONS: These
      results suggest that CTH is not associated with reducing oxidative injury, nor
      does it prevent ROS-induced cell damage. However, administration of vitamin E
      does reduce oxidative injury and prevent ROS-induced cell damage in a
      hemicastrated rat model.

PMID- 21093381
TI  - Gender-specific psychosocial outcome for women with epilepsy.
AB  - The objective of the study described here was to compare gender-specific
      differences of the personal impact of juvenile myoclonic epilepsy (JME) and
      temporal lobe epilepsy (TLE). We interviewed consecutive men and women with JME
      or TLE attending a tertiary epilepsy center to characterize their clinical and
      psychological profiles and details of employment and marriage. We recruited 150
      persons with JME (74 males) and 150 with TLE (80 males). There were no gender
      specific differences between men and women with respect to age at onset or
      semiology or frequency of seizures. Antiepileptic drug usage was comparable for
      both sexes except that fewer women with JME were prescribed valproate.
      Comorbidities, lower employment, and higher anxiety state were more frequent for
      women with epilepsy than for men with epilepsy. Females had more difficulty
      finding life partners compared with males. Women with epilepsy were at increased
      risk of divorce. Women with epilepsy have more problems with, marriage, mood, and
      employment as compared with men, even when the clinical profiles of their
      epilepsy syndromes are comparable.

PMID- 21093382
TI  - Acupuncture for carpal tunnel syndrome: a systematic review of randomized
      controlled trials.
AB  - Acupuncture is a widely used symptomatic treatment for carpal tunnel syndrome
      (CTS). The objective of this systematic review was to evaluate the evidence of
      the effectiveness of acupuncture and acupuncture-like treatments for CTS.
      Systematic searches were conducted on 11 electronic databases without language
      restrictions. All randomized controlled trials (RCTs) of acupuncture as a
      treatment of CTS were included. Methodological quality was assessed using the
      Cochrane risk of bias tool. Six RCTs met our inclusion criteria. Their
      methodological quality was generally low. Two RCTs compared the effectiveness of
      acupuncture with a sham control. The others used active controls. A meta-analysis
      of acupuncture versus steroid block therapy favored acupuncture (2 studies, n =
      144; risk ratio, 1.28; 95% CI, 1.08 to 1.52; P = .005; heterogeneity, I(2) = 10%)
      in terms of responder rate. Our systematic review and meta-analysis demonstrate
      that the evidence for acupuncture as a symptomatic therapy of CTS is encouraging
      but not convincing. The total number of included RCTs and their methodological
      quality were low. Further rigorous studies are required to establish whether
      acupuncture has therapeutic value for this indication. PERSPECTIVE: This
      systematic review of RCTs focused on clinical trials testing the effectiveness of
      acupuncture for CTS. The existing evidence is not convincing enough to suggest
      that acupuncture is an effective therapy for CTS. Further RCTs should overcome
      the limitation of previous studies.

PMID- 21093384
TI  - Lack of significant intraprostatic migration of stranded iodine-125 sources in
      prostate brachytherapy implants.
AB  - PURPOSE: Quantify the migration of iodine-125 RAPIDStrands ("strands") from Day 0
      to Day 30 postoperatively in patients treated with prostate brachytherapy.
      METHODS AND MATERIALS: Gold fiducial markers were inserted into the prostate
      before implants to serve as a fixed reference point within the prostate. Study
      patients underwent CT scans of the pelvis on Day 0 and Day 30 postimplant to
      image the prostate. In-house MATLAB software reconstructed each strand and
      determined its location relative to the center of mass of the fiducial markers.
      The recorded migration was taken to be the difference in these locations between
      Day 0 and Day 30. RESULTS: A total of 232 strands containing 1069 sources were
      implanted in 10 patients. Overall, 84% of strands migrated by less than 5mm in
      any direction. The collection of strands were displaced a mean distance of
      +0.22mm laterally (95% confidence interval [CI]: +0.08 to +0.37mm), -0.22mm
      posteriorly (95% CI: -0.51 to +0.06mm), and +0.41mm superiorly (95% CI: +0.03 to
      +0.79mm). Strands located in the anterior prostate demonstrated the greatest
      degree of migration in any direction, moving a mean of +1.55mm superiorly. These
      strands also moved a mean distance of 0.84mm posteriorly, whereas posteriorly
      located strands moved by a mean distance of 0.82mm anteriorly, consistent with
      movement because of the resolution of edema. CONCLUSIONS: This study did not
      identify any clinically significant patterns of mean migration of iodine-125
      RAPIDStrands from Day 0 to Day 30 postimplant.

PMID- 21093385
TI  - Use of customized-mold brachytherapy in the management of malignancies arising in
      the maxillary antrum after maxillectomy: a dosimetric analysis.
AB  - PURPOSE: To explore the feasibility of a intraoral mold high-dose rate (HDR)
      brachytherapy in the treatment of tumors arising in the maxillary antrum after
      maxillectomy and to describe the dosimetric profile of HDR brachytherapy in such
      an unusual location. METHODS AND MATERIALS: A customized mold with four 6-French
      catheters was designed and produced in transparent acrylic resin. The catheters
      formed a soft loop that allowed the passage of the HDR source. CT-based dose
      evaluation in several volumes of interest, including the gross tumor volume (GTV)
      and several organs at risk (OARs), such as the skin of the cheek, eyeball, lens,
      optic nerve, optic chiasm, and spinal cord was performed. RESULTS: Treatments
      were delivered uneventfully. A favorable OAR/GTV ratio was observed. The GTV
      D(90) was covered by the 3.8 Gy isodose (95% of the prescription isodose of 4 Gy)
      and the doses received by the OARs varied between 4% and 43% of the prescription
      isodose for the V1 cc of spinal cord and eyeball, respectively. The only
      structure that could not be adequately spared was the skin overlying the tumoral
      lesion that received between 94% and 107% of the prescription isodose (1.0 and
      0.5 cm(2) of skin, respectively). CONCLUSIONS: Intraoral mold-based HDR
      brachytherapy can be used to treat tumors involving the maxillary antrum provided
      that access is possible through a previous maxillectomy. A dose reduction of 4
      43% in several OARs, such as the spinal cord, pituitary gland, optic chiasm,
      optic nerve, eyeball, and lens, is obtained.

PMID- 21093386
TI  - Preparative separation of four individual flavonoids in Scutellaria barbata D.
      Don based on high selectivity polymeric adsorbents with different polarities.
AB  - The individual flavonoid component, scutellarin, scutellarein, luteolin and
      apigenin, in Scutellaria barbata plant was isolated based on the macro porous
      adsorbent with high adsorption selectivity. These adsorbents were synthesized
      based on the copolymerization of methyl acrylate and divinylbenzene (MA-co-DVB).
      So the polarity and the adsorption affinity of these adsorbents can be adjusted
      through changing MA content in the adsorbents. And then the ability of the
      adsorbent with different MA contents for isolation of these four individual
      flavonoid was also investigated. Adsorbents M2 and M4, with MA content of 25% and
      45%, respectively, demonstrated the best separation ability. Complete separation
      of the four flavone compounds was achieved in a continuous process based on
      combination of adsorbents with different polarities (M2 and M4). Gradient elution
      using adsorbent M4 separated the four flavonoids into three fractions, which were
      determined to contain scutellarin, scutellarein and a mixture of luteolin and
      apigenin. The latter was separated completely by adsorbent M2 subsequently. All
      four compounds were obtained at high resolution and high recovery yield (96.7%,
      94.1%, 95.8% and 93.8%, respectively), suggesting the efficiency of sequentially
      combined columns with different segregation patterns.

PMID- 21093383
TI  - Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal
      progenitor cells.
AB  - Epidermal and hair follicle development from surface ectodermal progenitor cells
      requires coordinated changes in gene expression. Histone deacetylases alter gene
      expression programs through modification of chromatin and transcription factors.
      We find that deletion of ectodermal Hdac1 and Hdac2 results in dramatic failure
      of hair follicle specification and epidermal proliferation and stratification,
      phenocopying loss of the key ectodermal transcription factor p63. Although
      expression of p63 and its positively regulated basal cell targets is maintained
      in Hdac1/2-deficient ectoderm, targets of p63-mediated repression, including p21,
      14-3-3sigma, and p16/INK4a, are ectopically expressed, and HDACs bind and are
      active at their promoter regions in normal undifferentiated keratinocytes. Mutant
      embryos display increased levels of acetylated p53, which opposes p63 functions,
      and p53 is required for HDAC inhibitor-mediated p21 expression in keratinocytes.
      Our data identify critical requirements for HDAC1/2 in epidermal development and
      indicate that HDAC1/2 directly mediate repressive functions of p63 and suppress
      p53 activity.

PMID- 21093387
TI  - Comparative analysis of the human urinary proteome by 1D SDS-PAGE and chip-HPLC
      MS/MS identification of the AACT putative urinary biomarker.
AB  - Urine is one of the most attractive analyte used for clinical diagnosis. NSCLC
      (non-small cell lung carcinoma), which includes adenocarcinoma, squamous cell
      carcinoma and large-cell carcinoma, is a leading cause of cancer-related deaths.
      In the present study, urinary proteomes of normal individuals and NSCLC patients
      were compared using 1D SDS-PAGE. From the distinctly differentially expressed
      bands in SDS-PAGE gel, 40 proteins were identified by chip-HPLC-MS/MS, including
      five proteins relevant to NSCLC. One of the selected proteins, alpha-1
      antichymotrypsin (AACT), was further validated in urine by western blot and in
      lung tissue by immunohistochemistry staining. Higher expression level of AACT in
      NSCLC patients was observed by western blot when compared with normal urine
      samples. Significantly, the NSCLC tumor tissue (18 out of 20 cases, 90%) showed a
      significantly higher expression level of AACT compared to adjacent non-tumor lung
      tissue (3 out of 20 cases, 15%). These results establish AACT as a potential
      biomarker for objective and non-invasive diagnosis of NSCLC in urine and the
      other four NSCLC-related proteins were also listed.

PMID- 21093388
TI  - High performance liquid chromatography assay with ultraviolet detection for
      moxifloxacin: validation and application to a pharmacokinetic study in Chinese
      volunteers.
AB  - A specific, sensitive and widely applicable high performance liquid
      chromatography with ultraviolet detection (HPLC-UV) method for the determination
      of moxifloxacin in human plasma was developed and validated in this study. The
      method involved a single step of liquid-liquid extraction with dichloromethane
      and the extraction yields more than 80% were achieved. The separation was
      performed on a common Kromasil C(8) column with an isocratic mobile phase. The
      total time was within 10 min per run. The calibration curve for moxifloxacin was
      linear in the concentration range of 0.05-5.0 MUg/ml with correlation coefficient
      of 0.9997. The developed method was validated with excellent specificity,
      sensitivity, accuracy, precision and stability. Using this developed method, the
      pharmacokinetics of moxifloxacin in healthy Chinese volunteers was studied.

PMID- 21093389
TI  - HPLC-MS/MS shotgun proteomic research of deer antlers with multiparallel protein
      extraction methods.
AB  - Deer antlers mature rapidly in 60 days, and subsequently shed in 5 days with
      rapid ossification. During this procedure, the function of deer antlers changes
      significantly. Therefore, the profiling of antler proteome is helpful to discover
      important growing and shedding regulation proteins, which might be of great
      significance for studying development and regeneration. In this study, a parallel
      protein extraction strategy was developed to extract proteins from antlers of red
      deer with five different lysis solutions, followed by shotgun proteomic analysis
      by microflow reversed-phase liquid chromatography/electrospray ionization/tandem
      mass spectrometry (MURPLC-ESI-MS/MS) with a 30 cm-long serially coupled
      microcolumn. Our experimental results showed that the identified proteins
      extracted by five kinds of lysis solution were complementary to each other. In
      total, 416 unique proteins were identified, with relative molecular masses from
      2000 to 600,000, and isoelectric points from 3.84 to 11.57. All these results
      demonstrate that the combination of parallel protein extraction strategy and
      MURPLC-ESI-MS/MS analysis with serially coupled long microcolumns might be of
      great significance for comprehensive proteomic research of deer antler.

PMID- 21093390
TI  - Determination of Bisphenol A and its chlorinated derivatives in placental tissue
      samples by liquid chromatography-tandem mass spectrometry.
AB  - The group of compounds commonly called endocrine disruptors covers a wide range
      of synthetic and natural substances able to alter the normal hormone function of
      wildlife and humans, consequently causing adverse health effects. Bisphenol A
      (BPA) and its chlorinated derivatives are some of these compounds. In this work,
      we propose a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      to determine these compounds in human placental tissue samples. The method
      involves an extraction phase of the extracts from the samples using ethyl
      acetate, followed by a clean-up phase by centrifugation prior to their
      quantification by LC-MS/MS using an atmospheric pressure chemical ionization
      (APCI) interface in the negative mode. Deuterated Bisphenol A (BPA-d(16)) was
      used as internal standard. Found detection limits (DL) ranged from 0.2 to 0.6 ng
      g(-1) and quantification limits (QL) from 0.5 to 2.0 ng g(-1) for Bisphenol A and
      its chlorinated derivatives, while inter- and intra-day variability was under
      8.1%. The method was validated using standard addition calibration and a spike
      recovery assay. Recovery rates for spiked samples ranged from 97% to 105%. This
      method was satisfactorily applied to the determination of BPA and its chlorinated
      derivatives in 49 placental tissue samples collected from women who live in the
      province of Granada (Spain).

PMID- 21093391
TI  - Ribavirin for chronic hepatitis C: and the mystery goes on.
AB  - Twenty years ago, ribavirin was first used in the treatment for chronic hepatitis
      C. After few years, ribavirin, in combination with interferon-alpha, showed a
      dramatic synergistic efficacy against hepatitis C virus infection, leading to
      viral clearance in about 50% of patients. Recent discovery of potent inhibitors
      of hepatitis C virus proteases did not replace ribavirin as the mainstay of
      combination therapy for chronic hepatitis C. Despite this fundamental role of
      ribavirin, many aspects of the mechanism of action and of the optimal dose and
      duration of therapy remain to be discovered or settled. In the present review,
      the authors recall the milestones in the history of ribavirin and try to shed
      light on the more relevant features of ribavirin action and utilization, and on
      the clinical problems encountered in managing and optimizing treatment for
      chronic hepatitis C. Finally, some potential off-label use of this drug in most
      difficult-to-treat subjects is pointed out. In conclusion, even if a sort of
      mystery surrounds ribavirin, its efficacy against hepatitis C virus infection
      fortunately remains lasting and stable.

PMID- 21093392
TI  - Usefulness of wireless capsule endoscopy in paediatric inflammatory bowel
      disease.
AB  - BACKGROUND: Small bowel endoscopy is critical in revealing an inflammatory bowel
      disease (IBD) previously undetected and in classifying the IBD patients, i.e.
      Crohn's disease or ulcerative colitis. METHODS: A prospective paediatric study on
      the usefulness of wireless capsule endoscopy (WCE) was performed in 117 children
      (age range: 4-17 years) with established or suspected IBD and compared with non
      endoscopic imaging tools. All patients underwent upper and lower gastrointestinal
      endoscopy. RESULTS: In Crohn's disease patients (CD, n=44), small bowel lesions
      were revealed by imaging tools in 8 and by WCE in 18 patients, respectively
      (p<0.01). No small bowel involvement was observed in 29 ulcerative colitis
      patients by both imaging tools and WCE. Of 26 unclassified IBD, small bowel
      lesions typical of Crohn's disease were detected by imaging in 7 and by WCE in 16
      (p<0.05). Of 18 patients with suspected IBD, small bowel lesions typical of
      Crohn's disease were observed in 9 with WCE, vs. only in 4 with imaging (p<0.01).
      No cases of capsule retention occurred. CONCLUSIONS: WCE is valuable in revealing
      small bowel lesions in children with a previous diagnosis of CD and unexplained
      clinical and laboratory data. It is also helpful in unclassified IBD patients.
      This tool can influence the management and the course of IBD.

PMID- 21093393
TI  - The impact of gender on the assessment of body checking behavior.
AB  - Body checking includes any behavior aimed at global or specific evaluations of
      appearance characteristics. Men and women are believed to express these behaviors
      differently, possibly reflecting different socialization. However, there has been
      no empirical test of the impact of gender on body checking. A total of 1024 male
      and female college students completed two measures of body checking, the Body
      Checking Questionnaire and the Male Body Checking Questionnaire. Using multiple
      group confirmatory factor analysis, differential item functioning (DIF) was
      explored in a composite of these measures. Two global latent factors were
      identified (female and male body checking severity), and there were expected
      gender differences in these factors even after controlling for DIF. Ten items
      were found to be unbiased by gender and provide a suitable brief measure of body
      checking for mixed gender research. Practical applications for body checking
      assessment and theoretical implications are discussed.

PMID- 21093394
TI  - Virtual muscularity: a content analysis of male video game characters.
AB  - The 150 top-selling video games were content analyzed to study representations of
      male bodies. Human males in the games were captured via screenshot and body parts
      measured. These measurements were then compared to anthropometric data drawn from
      a representative sample of 1120 North American men. Characters at high levels of
      photorealism were larger than the average American male, but these characters did
      not mirror the V-shaped ideal found in mainstream media. Characters at low levels
      of photorealism were also larger than the average American male, but these
      characters were so much larger that they appeared cartoonish. Idealized male
      characters were more likely to be found in games for children than in games for
      adults. Implications for cultivation theory are discussed.

PMID- 21093395
TI  - Mechanical failure of a Fogarty catheter in a microsurgical procedure: a case
      report.
AB  - Although microvascular free-tissue transfer has become a reliable reconstructive
      method, vascular compromise of the flap necessitating surgical exploration and
      attempts at flap salvage commonly occurs. Thrombectomy using Fogarty vascular
      catheters can be used in the setting of vascular pedicle thrombosis. However,
      this is not without potential complications. The following report describes a
      case in which the use of a Fogarty vascular catheter during a thrombectomy for
      microsurgical flap salvage resulted in complete separation of the balloon from
      the catheter.

PMID- 21093396
TI  - Re: Craniofacial reconstruction with bone and biomaterials: review over the last
      11 years. J Plast Reconstr Aesthet Surg 2010; 63: 1615-1623.

PMID- 21093397
TI  - Flexi-seal tube use for enteric fistula control in abdominal wall reconstruction.

PMID- 21093398
TI  - Simultaneous multi-site lymphaticovenular anastomoses for primary lower extremity
      and genital lymphoedema complicated with severe lymphorrhea.
AB  - Primary lower extremity and genital lymphoedema (GL) is difficult to manage,
      especially when complicated with severe lymphorrhea. With abundant experience of
      treatment for lower-extremity lymphoedema (LEL), we performed simultaneous multi
      site lymphaticovenular anastomoses (LVAs) for GL with severe lymphorrhea. In two
      cases of primary LEL and GL, LVAs were performed via 2-cm-long skin incisions
      using two to three operating microscopes under local anaesthesia. Symptoms of
      oedema and lymphorrhea improved clinically. LVA is a minimally invasive surgery,
      which is effective for the treatment of LEL and GL even in primary cases with
      severe lymphorrhea. Simultaneous multi-site LVAs can serve as the most effective
      therapy for lymphoedema.

PMID- 21093399
TI  - Prevalence of temporomandibular dysfunction in orthodontic treatment.
AB  - The aim of our study was to investigate the prevalence of temporomandibular
      dysfunction (TMD) during orthodontic treatment. MATERIAL AND METHOD: the study
      investigated all the patients receiving orthodontic treatment in the dentofacial
      orthopedic department in Casablanca in the course of the different stages of
      treatment over a 4-month period. We looked for a possible association between the
      presence of at least one sign of TMD, the Helkimo anamnesis index, the clinical
      Helkimo index and the following factors: age, gender, extractions, or not, of
      premolars, duration, type and stage of orthodontic treatment, molar and canine
      class, crowding, overjet, overbite and unilateral crossbite. Data were analysed
      using Epi-info 6.0.fr software. The analysis of the results was done using the
      Chi(2) test (P<0.05). RESULTS AND CONCLUSION: no statistically significant
      association could be established between TMD and the various factors under
      investigation with the exception of the association between gender and the
      Helkimo anamnesis index, stage of treatment and the Helkimo anamnesis index and
      the Angle molar class and the Helkimo clinical index.

PMID- 21093401
TI  - Drainage of iliopsoas muscle hematoma.

PMID- 21093402
TI  - Laparoscopic resection of gastric stromal tumor.

PMID- 21093403
TI  - Clinical practice guidelines.
AB  - Transferring results of research into clinical practice and their effective use
      for decisions in health care have become a major concern and are pivotal to
      quality improvement. Among the tools that have been developed are clinical
      practice guidelines (CPG). Developing reliable and valid recommendations requires
      a rigorous methodological approach that combines a systematic review of the
      results of clinical research with expert, pondered and explicit judgment.
      Guaranteeing applicability and implementation of these recommendations implies
      asking the question of how acceptable the recommendations are for the patient,
      the availability of the procedure and the expertise necessary in the specific
      context as well as identification of the organizational impact when put into
      action. CPG are a source of information not only for physicians but also for
      policy makers, insurance institutions, continued education programs and
      production of information for high quality decision making for patients.

PMID- 21093404
TI  - Plasmodium falciparum spliceosomal RNAs: 3' and 5' end processing.
AB  - The major spliceosomal small nuclear ribonucleoproteins (snRNPs) consist of snRNA
      (U1, U2, U4 or U5) and several proteins which can be unique or common to each
      snRNP particle. The common proteins are known as Sm proteins; they are crucial
      for RNP assembly and nuclear import of spliceosomal RNPs. This paper reports
      detecting the interaction between Plasmodium falciparum snRNAs and Sm proteins,
      and the usual 5' trimethylated caps on the snRNAs, by immunoprecipitation with
      specific antibodies. Furthermore, an unusual poly(A) tail was detected on these
      non-coding RNAs.

PMID- 21093405
TI  - High-performance liquid chromatography separation and intact mass analysis of
      detergent-solubilized integral membrane proteins.
AB  - We have developed a method for intact mass analysis of detergent-solubilized and
      purified integral membrane proteins using liquid chromatography-mass spectrometry
      (LC-MS) with methanol as the organic mobile phase. Membrane proteins and
      detergents are separated chromatographically during the isocratic stage of the
      gradient profile from a 150-mm C3 reversed-phase column. The mass accuracy is
      comparable to standard methods employed for soluble proteins; the sensitivity is
      10-fold lower, requiring 0.2-5 MUg of protein. The method is also compatible with
      our standard LC-MS method used for intact mass analysis of soluble proteins and
      may therefore be applied on a multiuser instrument or in a high-throughput
      environment.

PMID- 21093406
TI  - An (R)-specific N-methyltransferase involved in human morphine biosynthesis.
AB  - The biosynthesis of morphine, a stereochemically complex alkaloid, has been shown
      to occur in plants and animals. A search in the human genome for
      methyltransferases capable of catalyzing the N-methylation of benzylisoquinoline
      alkaloids, as biosynthetic precursors of morphine, yielded two enzymes, PNMT (EC
      2.1.1.28) and NMT (EC 2.1.1.49). Introduction of an N-terminal poly-histidine tag
      enabled purification of both proteins by immobilized metal affinity
      chromatography. Recombinant PNMT and NMT were characterized for their catalytic
      activity towards four benzylisoquinolines: tetrahydropapaveroline (THP), 6-O
      methyl-THP, 4'-O-methyl-THP and norreticuline. Human PNMT accepted none of the
      offered alkaloids and was only active with its established substrate,
      phenylethanolamine. The second enzyme, human NMT, converted all four
      benzylisoquinolines, however, with a strict preference for (R)-configured
      morphine precursors. Determination of kinetic parameters of NMT for the four (R)
      configured benzylisoquinoline alkaloids by LC-MS/MS revealed (R)-norreticuline to
      be the best substrate with an even higher catalytic activity as compared to the
      previously reported natural substrate tryptamine. In addition, isolation of the
      morphine precursor salutaridine from urine of mice injected (i.p.) with (R)-THP
      provides new evidence that the initial steps of morphine biosynthesis in mammals
      occur stereochemically and sequentially differently than in plants and suggests
      an involvement of the herein characterized (R)-specific NMT.

PMID- 21093407
TI  - The release of high mobility group box 1 in apoptosis is triggered by nucleosomal
      DNA fragmentation.
AB  - High mobility group box 1 (HMGB1) initially identified as a non-histone
      chromosomal protein, which mainly functions as chromatin structure and
      transcriptional regulation, has been recently reported to be secreted into
      extracellular milieu in necrosis and apoptosis, and act as a proinflammatory
      mediator. However, the mechanism by which apoptotic cells release HMGB1 is not
      clear. In this study, we found that staurosporine (apoptosis-inducer)-induced
      HMGB1 release was associated with nucleosomal DNA fragmentation catalyzed by
      caspase-activated DNase (CAD) in WEHI-231 cells. Importantly, this event was
      effectively attenuated by the treatment of a pan-caspase inhibitor, Z-VAD-fmk,
      and by the inhibition of CAD-mediated DNA fragmentation by the expression of
      caspase-resistant inhibitor of CAD (ICAD-CR). In WEHI-231/ICAD-CR and WEHI
      231/Puro cells, DNase gamma-catalyzed nucleosomal DNA fragmentation occurred by
      anti-IgM antibody treatment was critical for HMGB1 release. Furthermore, in DNase
      gamma stably-expressing HeLa S3 cells (HeLa S3/gamma), the release of HMGB1
      accompanied with nucleosomal DNA fragmentation was more apparent than that in
      parental HeLa S3 cells in which DNA fragmentation was scarcely observed. Taken
      together, these date suggest that nucleosomal DNA fragmentation catalyzed by CAD
      or DNase gamma plays a pivotal role in HMGB1 release.

PMID- 21093408
TI  - Ionic strength-dependent denaturation of Thermomyces lanuginosus lipase induced
      by SDS.
AB  - Triglyceride lipase from Thermomyces lanuginosus (TlL) has been reported to be
      resistant to denaturation by sodium dodecyl sulfate (SDS). We have found that at
      neutral pH, structural integrity is strongly dependent on ionic strength. In 10mM
      phosphate buffer and SDS, the lipase exhibits a far-UV CD spectrum similar to
      other proteins denatured in this surfactant while the near-UV CD spectrum shows a
      complete loss of tertiary structure, observations supported by steady state
      fluorescence spectroscopy. However, when increasing the ionic strength by the
      addition of NaCl, the lipase was rendered resistant towards SDS denaturation, as
      observed by all techniques employed. The effect of salt on the critical micelle
      concentration (CMC) of SDS was observed to correlate with the effect on the
      degree of SDS-induced denaturation. This finding is compatible with the notion
      that the concentration of SDS monomers is a crucial factor for SDS-lipase
      interactions. The presented results are important for the understanding and
      improvement of protein stability in surfactant systems.

PMID- 21093409
TI  - Molecular cloning and characterization of a hamster Cav1.3 Ca2+ channel variant
      with a long carboxyl terminus.
AB  - We have cloned a hamster Cav1.3 variant with a long carboxyl terminus. This
      differs from the first hamster Cav1.3 clone which has a short carboxyl terminus.
      When relative expression levels of the two variants were examined using
      quantitative RT-PCR, the long Cav1.3 transcripts were detected abundantly in the
      brain and testis, moderately in the heart, pancreas, and kidney, and weakly in
      the lung. Comparatively, the short Cav1.3 transcripts were detected less
      abundantly in most of the tissues. The two Cav1.3 variants were reconstituted in
      Xenopus oocytes and their electrophysiological properties were characterized
      using a two-electrode voltage clamping method. The long Cav1.3 variant was ~5
      fold better expressed than the short Cav1.3 variant. When Ca2+ was used as a
      charge carrier, the long Cav1.3 variant containing an IQ (Ile-Gln) motif
      displayed strong calcium-dependent inactivation, while the short variant that was
      deficient of an IQ motif showed little calcium-dependent inactivation.
      Examination of other biophysical properties revealed that potentials for
      activation threshold, peak current, and half-activation and inactivation of the
      long Cav1.3 were significantly lower than those of the short Cav1.3. These
      findings suggest that the long carboxyl tail plays crucial roles in not only
      facilitating calcium-dependent inactivation, but also improving expression and
      negative shifting of the activation and inactivation properties.

PMID- 21093410
TI  - MDM2 promotes the proteasomal degradation of p73 through the interaction with
      Itch in HeLa cells.
AB  - It has been shown that MDM2 inhibits the transcriptional and pro-apoptotic
      activities of p73 but does not promote its proteasomal degradation. In this
      study, we found that MDM2 indirectly induces the degradation of p73 through the
      interaction with Itch in HeLa cells. During adriamycin (ADR)-mediated apoptosis,
      p53 and p73 were induced to stabilize in association with a significant reduction
      of MDM2 and Itch, suggesting that, in addition to Itch, MDM2 could also be
      involved in the stability control of p73. As expected, forced expression of MDM2
      resulted in a remarkable reduction of p73. MDM2-mediated degradation of p73 was
      inhibited by MG-132. Intriguingly, siRNA-mediated knockdown of Itch significantly
      attenuated the negative effect of MDM2 on p73. Additionally, MDM2 bound to Itch
      in HeLa cells but not in H1299 cells. Collectively, our present findings suggest
      that MDM2 promotes Itch-mediated degradation of p73 through the interaction with
      Itch in HeLa cells.

PMID- 21093411
TI  - Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition
      of nuclear factor kappaB p65 activation.
AB  - Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis
      Georgi. We aimed to evaluate the neuroprotective effects of baicalin against
      cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle
      cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h.
      Baicalin at doses of 50, 100 and 200 mg/kg was intravenously injected after
      ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was
      scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was
      performed to analyze the histopathological changes of cortex and hippocampus
      neurons. We examined the levels of NF-kappaB p65 in ischemic cortexes by Western
      blot analysis and RT-PCR assay. The results showed that the neurological deficit
      scores were significantly decreased from 2.0 +/- 0.7 to 1.2 +/- 0.4 and the
      volume of infarction was reduced by 25% after baicalin injection.
      Histopathological examination showed that the increase of neurons with pycnotic
      shape and condensed nuclear in cortex and hippocampus were not observed in
      baicalin treated animals. Further examination showed that NF-kappaB p65 in cortex
      was increased after ischemia reperfusion injury, indicating the molecular
      mechanism of ischemia reperfusion injury. The level of NF-kappaB p65 was
      decreased by 73% after baicalin treatment. These results suggest that baicalin
      might be useful as a potential neuroprotective agent in stroke therapy. The
      neuroprotective effects of baicalin may relate to inhibition of NF-kappaB p65.

PMID- 21093412
TI  - Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T
      lymphocytes influence viral entry co-receptor expression and susceptibility to
      superinfection.
AB  - HIV-1 Nef is a key factor for pathogenesis and is known to down-regulate
      functionally important molecules, including viral entry co-receptor CCR5 and
      CXCR4, from the surface of HIV-infected cells. Some of these Nef activities are
      mediated by the well-conserved proline-rich region of Nef, and this region is
      highly targeted by cytotoxic T lymphocytes (CTLs). In the present study, we asked
      whether Nef variants selected under CTL-mediated selective pressure in vivo may
      constrain these important Nef activities. The analysis of autologous nef
      sequences isolated from a cohort of total 235 subjects in Japan revealed that the
      subjects showing amino acid variations, such as Arg75Thr and Tyr85Phe, located
      within the proline-rich region were significantly over-represented by those
      having HLA-B*3501. CTL assays corroborated that these mutations conferred escape
      from HLA-B(*)3501-restricted CTLs. The Arg75Thr variant Nef selectively impaired
      CCR5, but not CXCR4, down-regulation activity from the cell surface; whereas the
      Tyr85Phe variant Nef affected neither CCR5 nor CXCR4 down-regulation activity.
      Moreover, the cells expressing the Arg75Thr variant Nef significantly impaired
      protection from superinfection by CCR5-tropic, but not CXCR4-tropic, viruses.
      These results highlighted the importance of certain Nef-specific CTLs in
      modulation of viral co-receptor down-regulation activity and protection from HIV
      1 superinfection, providing us with additional insight into vaccine design.

PMID- 21093413
TI  - Association of the functional KL-VS variant of Klotho gene with early-onset
      ischemic stroke.
AB  - Genetic variants of Klotho have been reported to be associated with human
      longevity and atherosclerotic vascular events and risk factors. However, very few
      studies have explored their association with ischemic stroke. We hypothesized
      that the functional KL-VS and the exonic C1818T variants of Klotho gene may be
      associated with ischemic stroke in Indian population. We enrolled a total of 460
      patients with ischemic stroke and 574 age- and gender-matched controls for the
      study. Genotyping was done by polymerase chain reaction and restriction fragment
      length polymorphism. Contrary to other Asian reports, KL-VS variant was
      polymorphic in our population, with a frequency distribution similar to that of
      Caucasians. The frequency distribution of the C1818T variant was similar to
      previously reports in Asians. A differential effect of age on association of
      Klotho KL-VS variant with ischemic stroke was observed. In subjects aged <=40
      years, the KL-VS homozygotes, 352FF and 352VV, had ~1.5-fold (OR=1.57; 95% CI:
      1.02-2.40, p=0.038) and ~3-fold (OR=3.29; 95%CI: 1.02-10.56, p=0.046) higher risk
      of stroke compared to heterozygotes, whereas in the older group (aged >40 years)
      no significant association was observed. The C1818T variant was not associated
      with ischemic stroke. We conclude that KL-VS homozygosity could contribute to
      early-onset stroke in India. Larger studies in other ethnic populations are
      warranted to determine the role of these gene variants in the etiology of stroke
      occurring in the young.

PMID- 21093414
TI  - Snail-mediated regulation of reactive oxygen species in ARCaP human prostate
      cancer cells.
AB  - Reactive oxygen species increases in various diseases including cancer and has
      been associated with induction of epithelial-mesenchymal transition (EMT), as
      evidenced by decrease in cell adhesion-associated molecules like E-cadherin, and
      increase in mesenchymal markers like vimentin. We investigated the molecular
      mechanisms by which Snail transcription factor, an inducer of EMT, promotes tumor
      aggressiveness utilizing ARCaP prostate cancer cell line. An EMT model created by
      Snail overexpression in ARCaP cells was associated with decreased E-cadherin and
      increased vimentin. Moreover, Snail-expressing cells displayed increased
      concentration of reactive oxygen species (ROS), specifically, superoxide and
      hydrogen peroxide, in vitro and in vivo. Real Time PCR profiling demonstrated
      increased expression of oxidative stress-responsive genes, such as aldehyde
      oxidase I, in response to Snail. The ROS scavenger, N-acetyl cysteine partially
      reversed Snail-mediated EMT after 7 days characterized by increased E-cadherin
      levels and decreased ERK activity, while treatment with the MEK inhibitor, UO126,
      resulted in a more marked effect by 3 days, characterized by cells returning back
      to the epithelial morphology and increased E-cadherin. In conclusion, this study
      shows for the first time that Snail transcription factor can regulate oxidative
      stress enzymes and increase ROS-mediated EMT regulated in part by ERK activation.
      Therefore, Snail may be an attractive molecule for therapeutic targeting to
      prevent tumor progression in human prostate cancer.

PMID- 21093415
TI  - Reexpression of ARHI inhibits tumor growth and angiogenesis and impairs the
      mTOR/VEGF pathway in hepatocellular carcinoma.
AB  - The Ras-related tumor suppressor gene aplasia Ras homolog member I (ARHI) is
      frequently downregulated in many types of cancer, including hepatocellular
      carcinoma (HCC). In this study, we sought to explore the therapeutic implications
      of ARHI reconstitution in the treatment of HCC. We generated stable cell lines
      overexpressing ARHI in Hep3B and SK-Hep1 cells, both of which lack endogenous
      ARHI. The effects of ARHI reexpression on tumor growth and angiogenesis were
      assessed. Given the key role of mammalian target of rapamycin (mTOR) signaling in
      HCC progression, we also tested whether ARHI overexpression affected the mTOR
      pathway. Forced expression of ARHI resulted in a significant inhibition of the
      proliferation of both Hep3B and SK-Hep1 cells compared to control cells (P<0.01).
      Cell cycle analysis revealed a G0-G1 arrest induced by ARHI reexpression.
      Moreover, ARHI reexpression significantly retarded Hep3B xenograft growth in
      vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31
      stained microvessel count. Western blot analysis of the xenografts showed that
      ARHI overexpression substantially reduced the phosphorylation of two mTOR
      substrates, S6K1 and 4E-BP1, indicative of an inactivation of the mTOR pathway.
      Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia
      inducible factor 1 alpha and vascular endothelial growth factor, were
      significantly downregulated. These data highlighted an important role for ARHI in
      controlling HCC growth and angiogenesis, therefore offering a possible
      therapeutic strategy against this malignancy.

PMID- 21093417
TI  - Schizophrenia risk genes: Implications for future drug development and discovery.
AB  - Present-day development of improved treatments for schizophrenia is hindered by
      uncertain models of disease, inter-individual response variability in clinical
      trials and a paucity of sensitive measures of treatment effects. Findings from
      genetic research emphasize the potential for schizophrenia risk genes to help
      develop focused treatments, discover new drug targets and provide markers of
      clinical subtypes. Advances in genetic technologies also provide novel modes of
      drug discovery in schizophrenia such as transcriptomics, epigenetics and
      transgenic animal models. In this review, we discuss proven and proposed ways
      risk genes can be used to enhance the development and discovery of treatments for
      schizophrenia and highlight key studies in these approaches.

PMID- 21093418
TI  - Orally active glutamate carboxypeptidase II inhibitor 2-MPPA attenuates
      dizocilpine-induced prepulse inhibition deficits in mice.
AB  - Glutamate carboxypeptidase II (GCP II) is a glial enzyme responsible for the
      hydrolysis of N-acetylaspartylglutamate (NAAG) into glutamate and N
      acetylaspartate (NAA). Abnormalities in glutamate neurotransmission are
      implicated in the pathophysiology of schizophrenia. In this study, we examined
      the effects of a novel, orally active GCP II inhibitor, 2-(3
      mercaptopropyl)pentanedioic acid (2-MPPA), on the prepulse inhibition (PPI)
      deficits after administration of the N-methyl-d-aspartate (NMDA) receptor
      antagonist dizocilpine. Oral administration of 2-MPPA (10, 30 or 100mg/kg)
      significantly attenuated dizocilpine (0.1mg/kg)-induced PPI deficits in mice, in
      a dose dependent manner. Furthermore, the efficacy of 2-MPPA on dizocilpine
      induced PPI deficits was significantly antagonized by pretreatment with the
      selective group II metabotropic glutamate receptor (mGluR) antagonist LY341495
      (1.0mg/kg). In the same model, however, the selective group II mGluR agonist
      LY354740 (3, 10 or 30 mg/kg) significantly attenuated dizocilpine-induced PPI
      deficits at only one dose and prepulse intensity. Our findings suggest that GCP
      II inhibition may be useful therapeutic strategy for schizophrenia. From a
      mechanistic perspective, while increased NAAG and activation of group II mGluRs
      may contribute to the therapeutic efficacy of 2-MPPA, it is likely that
      additional pharmacological activities are also involved.

PMID- 21093416
TI  - Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and
      expression: the hunt goes on.
AB  - Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated enzyme
      displaying esterase and lactonase activity. PON1 hydrolyzes several
      organophosphorus (OP) insecticides and nerve agents, a number of exogenous and
      endogenous lactones, and metabolizes toxic oxidized lipids of low density
      lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining
      susceptibility to OP toxicity, cardiovascular diseases and several other
      diseases. Serum PON1 activity in a given population can vary by at least 40-fold.
      Most of this variation can be accounted for by genetic polymorphisms in the
      coding region (Q192R, L55M) and in the promoter region (T-108C). However,
      exogenous factors may also modulate PON1 activity and/or level of expression.
      This paper examines various factors that have been found to positively modulate
      PON1. Certain drugs (e.g. hypolipemic and anti-diabetic compounds), dietary
      factors (antioxidants, polyphenols), and life-style factors (moderate alcohol
      consumption) appear to increase PON1 activity. Given the relevance of PON1 in
      protecting from certain environmental exposure and from cardiovascular and other
      diseases, there is a need for further mechanistic, animal, and clinical research
      in this area, and for consideration of possible alternative strategies for
      increasing the levels and activity of PON1.

PMID- 21093419
TI  - Parasympathetic reflex vasodilatation in the masseter muscle compensates for
      carotid hypoperfusion during the vagus-mediated depressor response.
AB  - Parasympathetic vasodilatation in the orofacial area is thought to be an
      important factor in the regulation of blood flow in the common carotid artery
      (CABF), and disturbances in parasympathetic vasodilatations may be related to
      impairment of the CABF inducing craniofacial ischemia. We hypothesized that the
      parasympathetic vasodilatation in the masseter muscle evoked by a vagus-mediated
      reflex is involved in the maintenance of the CABF during the vagus-mediated
      depressor response. In the present study, we compared changes in blood flow in
      the masseter muscle (MBF) and CABF, and systemic arterial blood pressure (SABP)
      evoked by electrical stimulation of the central cut end of the cervical vagus
      nerve (cVN) in anesthetized and sympathectomized rats. Electrical stimulation of
      the cVN in the sympathectomized animals caused an increase in MBF followed by a
      CABF increase, although it simultaneously induced a decrease in SABP. These
      increases in blood flow changed to decreases after intravenous administration of
      atropine (100 MUg/kg), while pretreatment with atropine had no effect on the
      changes in SABP. Microinjection (50 nl/site) of the muscimol (1mM), into the
      nucleus of the solitary tract, which is involved in reflex cardiovascular
      regulation, markedly inhibited the cVN stimulation-induced MBF increase. Our
      results indicate that vagal-parasympathetic vasodilatation in the masseter muscle
      compensates for carotid hypoperfusion during the vagus-mediated depressor
      response, and that GABAergic neurons may be involved in the inhibition of this
      response. This inhibition may result in the impairment of CABF, suggesting an
      important role in the etiology of neurally mediated syncope.

PMID- 21093420
TI  - Increased excitability and reduced intracortical inhibition in the ipsilateral
      primary motor cortex during a fine-motor manipulation task.
AB  - The effects of a sensorimotor task on ipsilateral primary motor cortex (ipsi-M1)
      excitability mediated via the transcallosal pathway, including the changes in
      short-interval intracortical inhibition (SICI) and intracortical facilitation
      (ICF), were examined in ten right-handed subjects. Transcranial magnetic
      stimulation (TMS) was delivered to evoke a motor evoked potential (MEP) from the
      first dorsal interosseous (FDI). The test-TMS intensity was adjusted to around
      120% of the resting motor threshold (rMT). For the paired-pulse TMS paradigm, the
      conditioning-TMS intensity was set to 80% of the rMT, and the interstimulus
      interval was fixed at 3 ms for SICI and 12 ms for ICF. As a sensorimotor task, a
      fine-motor manipulation (FM) task (using chopsticks to pick up, transport, and
      release glass balls) was adopted. In addition, a pseudo-FM (pFM) task was also
      performed as a control task. These tasks were carried out using each hand
      separately. The MEPs evoked during the FM task were markedly increased compared
      with those evoked during the pFM task, and these effects were not dependent on
      the electromyographic activity of the FDI performing these tasks. SICI was
      significantly decreased during the FM task, indicating disinhibition of the ipsi
      M1, and these effects were also noted when the subjects used their non-dominant
      hand. The present findings suggest that the differences between the effects of
      the FM and pFM tasks on ipsi-M1 excitability were caused by their property.

PMID- 21093421
TI  - Elevated oxidized low-density lipoprotein concentrations in postmenopausal women
      with the metabolic syndrome.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) and oxidized low-density
      lipoprotein (ox-LDL) are probably associated with atherosclerosis and coronary
      artery disease. The influence of LDL-C and ox-LDL on metabolic syndrome among
      healthy, postmenopausal women has not been well studied. The aim of this study
      was to assess the association between LDL-C, ox-LDL, and metabolic syndrome in
      postmenopausal women. METHODS: The study design was a cross-sectional study. A
      total of 1309 postmenopausal women (355 with metabolic syndrome and 954 without
      metabolic syndrome) aged 60-79 years were included. Lipid profiles, glucose, ox
      LDL, adiponectin, interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha
      concentrations were measured. RESULTS: Plasma ox-LDL levels were higher in
      subjects with metabolic syndrome, when compared without metabolic syndrome
      subjects. A multiple linear regression analysis revealed that ox-LDL was
      significantly associated with high-density lipoprotein cholesterol, LDL-C,
      triglycerides, and adiponectin. After a multivariable adjustment, the odds ratios
      for the second, third, and fourth quartiles of ox-LDL in metabolic syndrome
      compared with the lowest quartile were 1.76 (95% confidence interval [CI], 1.15
      2.70), 2.45 (95% CI, 1.58-3.79), and 3.98 (95% CI, 2.52-6.28), respectively. LDL
      levels were not significantly associated with metabolic syndrome. CONCLUSIONS: Ox
      LDL concentration was associated with metabolic syndrome in postmenopausal women.
      These findings suggest that high ox-LDL levels are associated with high
      cardiovascular risk in postmenopausal women with metabolic syndrome.

PMID- 21093422
TI  - Comparative study on secondary structural changes in diabetic and non-diabetic
      human finger nail specimen by using FTIR spectra.
AB  - BACKGROUND: In human anatomy, a nail is a hornlike envelope covering the dorsal
      aspect of the terminal phalanges of fingers and toes. Nail disorders are most
      common among the geriatric population. Diabetes mellitus is also supposed to
      affect the condition of nails. Acceptable differences in infrared (IR) spectra of
      chronic and acute diabetes mellitus patient fingernail specimens compared to
      control normal specimens were investigated in this study. METHODS: Using a
      Nicolet 360 Fourier Transform Infra Red (FTIR) spectrometer, the spectra of the
      nails of diabetics and normal specimens were recorded. RESULT: In the case of non
      diabetic patients, the amide I band was observed <1640 cm(-1) (1626, 1632, and
      1638 cm(-1)). The bands around 1637 cm(-1), were attributable to amide I of beta
      sheet structures. Amide II bands were absent in all the non-diabetic patients.
      Amide III bands around 1250 cm(-1) were observed both in diabetic and non
      diabetic patients. In all the diabetic patients, a peak of <500 cm(-1),
      particularly around 468 cm(-1), was observed. CONCLUSION: The proteins in the
      nails of diabetic patients contain alpha-helical structure, including the
      presence of amide II bonds. Alkyl thiolated structures are observed. Nails of non
      diabetic patients do not have the amide II structures.

PMID- 21093423
TI  - Clinical performance of a new point-of-care cardiac troponin I assay compared to
      three laboratory troponin assays.
AB  - BACKGROUND: Studies of cardiac markers in diagnosing acute myocardial infarction
      (AMI) have mostly been performed using central laboratory platforms. The AQT90
      FLEX TnI (troponin I) assay is designed for quantitative point of care testing
      (POCT). This study evaluated clinical performance in diagnosing AMI of the AQT90
      FLEX TnI POCT assay compared with central laboratory troponin assays. METHODS:
      The study included 458 chest pain patients. Blood samples were obtained on
      admission and after 6-9h. Blood was analyzed using the following assays: AQT90
      FLEX TnI, Access AccuTnI, Abbott AxSYM ADV, Roche cTnT, Roche CKMBmass. Patients
      were diagnosed with AMI according to the new universal definition of AMI.
      RESULTS: The performance of the AQT90 FLEX TnI assay on admission was equivalent
      to the Abbott AxSYM ADV cTnI but inferior to the AccuTnI. After 6-9 h both
      laboratory based assays were superior. The AQT90 FLEX TnI had a negative
      predictive value (NPV) of 90 and 96% (admission; 6-9 h). No statistical
      differences were seen in receiver operating characteristics analysis.
      CONCLUSIONS: The AQT90 FLEX TnI POCT assay was marginally inferior to the two
      laboratory based assays of cTnI in diagnosing AMI. A high (NPV) may make this
      assay suitable as a rule out marker.

PMID- 21093424
TI  - Cell-free miR-24 and miR-30d, potential diagnostic biomarkers in malignant
      effusions.
AB  - OBJECTIVES: The study was trying to figure out the possible role of cell-free miR
      24 and miR-30d as diagnostic biomarkers for malignant effusions. METHODS: A total
      of 110 effusion samples (28 benign and 82 malignant) were collected and cell-free
      total RNA was extracted. Quantitative RT-PCR was carried out to measure the
      expression levels of miR-24 and miR-30d, with an exogenous supplemented plant
      miRNA, ath-miR156a as the reference RNA. RESULTS: Malignant pleural effusions had
      higher expression levels of cell-free miR-24 and miR-30d than benign effusions.
      In the ascites group, only miR-30d was found to be significantly up-regulated in
      the supernatant of effusions. Combination of cell-free miR-24 and miR-30d could
      discriminate malignant ascites from benign with improved potency comparing to
      single miR-30d. CONCLUSIONS: Cell-free miR-30d and miR-24 are potential
      diagnostic biomarkers for malignant and benign effusions.

PMID- 21093425
TI  - CD40/SCD40 imbalance in hemodialysis patients.

PMID- 21093426
TI  - Genistein stimulates duodenal HCO(3)(-) secretion through PI3K pathway in mice.
AB  - Genistein has been proposed as a promising pharmacotherapeutic for cystic
      fibrosis. We recently found that genistein stimulates murine duodenal HCO(3)(-)
      secretion through cystic fibrosis transmembrane conductance regulator (CFTR). The
      aim of the present study was to determine the intracellular signal pathways
      involved in genistein-stimulated duodenal HCO(3)(-) secretion. Murine duodenal
      mucosal HCO(3)(-) secretion was examined in vitro in Ussing chambers by the pH
      stat technique. The results showed that neither cAMP-dependent signal pathway
      inhibitors MDL-12330A and KT-5720, nor cGMP signal pathway inhibitors NS2028 and
      KT5823, nor calcium signal pathway inhibitors verapamil and W-13, altered
      genistein-stimulated duodenal HCO(3)(-) secretion. In calcium-free solution,
      genistein-stimulated duodenal HCO(3)(-) secretion was not altered either.
      Vanadate, an inhibitor of protein tyrosine phosphatase, only partially inhibited
      genistein-stimulated duodenal HCO(3)(-) secretion. However, both wortmannin and
      LY294002, two structurally and mechanistically distinct phosphatidylinositol 3
      kinase (PI3K) inhibitors, markedly inhibited genistein-stimulated duodenal
      HCO(3)(-) secretion. Genistein increased duodenal mucosal PI3K activity and
      induced the phosphorylation of Akt, a signaling molecule downstream of PI3K,
      which was again inhibited by wortmannin. Estrogen receptor antagonist,
      ICI182,780, also markedly inhibited genistein-stimulated duodenal HCO(3)(-)
      secretion and genistein-induced PI3K activity increase in duodenal mucosa. These
      results demonstrate that genistein stimulates duodenal HCO(3)(-) secretion mainly
      through estrogen receptor and PI3K-dependent pathway. These findings contribute
      to the understanding of the molecular mechanism of genistein-induced anion
      secretion and further pharmacotherapeutic development and use of genistein or
      related substances in the treatment of diseases of epithelial tissues.

PMID- 21093427
TI  - Aripiprazole protects cortical neurons from glutamate toxicity.
AB  - Neurodegeneration is thought to be a component of schizophrenia pathology, and
      some antipsychotics appear to slow degenerative changes in patients.
      Aripiprazole, the first partial dopamine D(2) receptor agonist approved for the
      treatment of schizophrenia, is suggested to be neuroprotective based on non
      clinical studies using transformed cell lines and in vivo stress and lesion
      paradigms. However, aripiprazole-induced neuroprotection has not been studied in
      a neuronal glutamate toxicity assay, which may model aspects of neurodegeneration
      occurring in schizophrenia. This study examined whether therapeutically relevant
      concentrations of aripiprazole protect rat embryonic cortical neurons from
      glutamate toxicity in biochemical and high-content imaging assays. Aripiprazole
      inhibited glutamate-induced neurotoxicity by 40% in a 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, in contrast to risperidone and
      olanzapine, which had little neuroprotective activity. This neuroprotective
      effect of aripiprazole was not mediated by the activation of serotonin 5-HT(1A)
      or dopamine D(2) receptors, Akt or glycogen-synthase kinase-3beta signaling (GSK
      3beta), or through the inhibition of poly-ADP ribose polymerase (PARP). Further
      experiments are required to determine the biochemical nature of aripiprazole
      induced neuroprotection and whether any such activity might have clinical
      relevance.

PMID- 21093428
TI  - Jaceosidin inhibits contact hypersensitivity in mice via down-regulating IFN
      gamma/STAT1/T-bet signaling in T cells.
AB  - In the present study, we aimed to investigate the immunosuppressive activity of
      jaceosidin, a flavone isolated from Artemisia vestita, on T lymphocytes both in
      vitro and in vivo, and further explore its potential molecular mechanism.
      Jaceosidin exerted a significant inhibition on the T cell proliferation and
      activation induced by concanavalin A (Con A) in a concentration-dependent manner
      and it also inhibited the secretion of the proinflammatory cytokines such as IL
      2, TNF-alpha and IFN-gamma of activated T cells. Further study showed that
      jaceosidin down-regulated STAT1 activation and T-bet expression in activated T
      cells. Moreover, in order to investigate the immunosuppressive effect of
      jaceosidin in vivo, the picryl chloride (PCl)-induced ear contact dermatitis
      model was performed on BALB/c mice. Jaceosidin significantly ameliorated PCl
      induced ear swelling in a dose-dependent manner, which was due to its inhibition
      of the STAT1/T-bet signaling pathway. In summary, these findings suggest that
      jaceosidin exerts its immunosuppressive effect both in vitro and in vivo through
      inhibiting T cell proliferation and activation, which is closely associated with
      its potent down-regulation of the IFN-gamma/STAT1/T-bet signaling pathway.

PMID- 21093429
TI  - Histamine H(4) receptor antagonism inhibits allergen-specific T-cell responses
      mediated by human dendritic cells.
AB  - Dendritic cells are potential targets in allergy therapy as they, under the
      influence of their microenvironment, regulate T-cell responses. Histamine has
      been shown to promote Th2 polarization by dendritic cells. However, neither the
      mechanism nor the functionality of the different histamine receptors in this
      process has been fully elucidated. The aim of the present study was to identify
      factors involved in histamine-mediated dendritic cell activation as well as to
      study dendritic cell expression of histamine H(1) and H(4) receptors and their
      influence on allergen-specific T-cell responses in grass pollen allergy.
      Assessment of dendritic cell gene regulation by histamine using mRNA microarrays
      demonstrated that histamine alters many immunoregulatory genes of which the
      majority are novel in this context. Additionally, immunocytochemical stainings
      showed protein expression of histamine H(1) and H(4) receptors on dendritic cells
      from healthy and allergic donors. Furthermore, histamine H(1) and H(4) receptor
      antagonists (pyrilamine/N-(4-methoxybenzyl)-N',N'-dimethyl-N-pyridin-2-ylethane
      1,2-diamine and JNJ7777120/1-[(5-chloro-1H-indol-2-yl)carbonyl]-4
      methylpiperazine, respectively) were shown to influence histamine-induced
      dendritic cell maturation. Interestingly, JNJ7777120 inhibited dendritic cells'
      capacity to induce allergen-specific T-cell proliferation. In conclusion, H(4)
      receptor antagonism suppressed DC-induced, allergen-specific T-cell responses in
      humans and might thus inhibit allergic responses. This finding indicates that the
      H(4) receptor is a potential treatment target in human allergic conditions.

PMID- 21093430
TI  - Opioid receptor agonist Eribis peptide 94 reduces infarct size in different
      porcine models for myocardial ischaemia and reperfusion.
AB  - Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with
      the MU- and delta-opioid receptors. The purpose of the present study was to
      examine the cardioprotective potential of EP 94 in two clinically relevant
      porcine models of myocardial ischaemia and reperfusion, and to investigate if
      such an effect is associated with an increased expression of endothelial nitric
      oxide synthase (eNOS). Forty-one anesthetized pigs underwent 40min of coronary
      occlusion followed by 4h of reperfusion. In Protocol I, balloon occlusion of the
      left anterior descending artery was performed with concurrent intravenous
      administration of (A) vehicle (n=7), (B) EP 94 (1ug/kg) after 5, 12, 19 and 26min
      of ischaemia (n=4) or (C) EP 94 (1ug/kg) after 26, 33, 40min of ischaemia (n=6).
      In Protocol II, open-chest pigs were administered (D) vehicle (n=6) or (E)
      0.2ug/kg/min of EP 94 (n=6) through an intracoronary infusion into the
      jeopardized myocardium, started after 30min of ischaemia and maintained for
      15min. The hearts were stained and the protein content of eNOS measured. EP 94
      reduces infarct size when administered both early and late during ischaemia
      compared with vehicle (infarct size group A 61.6+/-2%, group B 50.2+/-3% and
      group C 49.2+/-2%, respectively, P<0.05), as well as when infused intracoronary
      (infarct size group D 82.2+/-3.9% and group E 61.2+/-2.5% respectively, P<0.01).
      Phosphorylated eNOS Ser(1177) in relation to total eNOS was significantly
      increased in the group administered EP 94, indicating activation of nitric oxide
      production.

PMID- 21093431
TI  - DHF-18, a new synthetic flavonoid, induced a mitochondrial-mediated apoptosis of
      hepatocarcinoma cells in vivo and in vitro.
AB  - A new synthetic flavonoid DHF-18, synthesized with a piperazine substitution, has
      been recently found to show potent anti-tumor activities both in vivo and in
      vitro. In this study, we demonstrated that DHF-18 significantly inhibited tumor
      growth in mice inoculated with Heps hepatoma cells without evident toxicity.
      After the treatment of 40mg/kg DHF-18, the inhibitory rate of tumor weight was
      53.69%. To investigate whether apoptosis induction contributed to the anti-tumor
      effects of DHF-18, DAPI (diamidino-phenyl-indole) staining and Annexin V/PI
      (Propidium iodide) double staining were performed in our tests. The data showed
      that DHF-18 could induce the apoptosis cell death in HepG2 cells. Moreover, the
      apparent increase of intracellular reactive oxygen species levels and the
      reduction of mitochondria DeltaPsim were both observed in HepG2 cells after DHF
      18 treatment. Meanwhile, the transposition of apoptotic inducing factor (AIF)
      from mitochondria to nuclei, the release of cytochrome c from mitochondria and
      the activation of caspase-3, -9 were also detected, indicating that DHF-18 may
      induce apoptosis through a mitochondrial-mediated pathway. Additionally, DHF-18
      decreased the expression of Bcl-2 protein, whereas the levels of Bax and Bak were
      found to increase after DHF-18 treatment. Moreover, the activation of caspase-8,
      the increase of TNF-R1 (Tumor necrosis factor receptor) and Bid were found. Taken
      together, our results suggested that DHF-18 may induce HeG2 cells apoptosis
      through a mitochondrial-dependent and independent pathway.

PMID- 21093432
TI  - Kruppel-like factor 7 is required for olfactory bulb dopaminergic neuron
      development.
AB  - Kruppel-like factor 7 (KLF7) belongs to the large family of KLF transcription
      factors, which comprises at least 17 members. Within this family, KLF7 is unique
      since its expression is strictly restricted within the nervous system during
      development. We have previously shown that KLF7 is required for neuronal
      morphogenesis and axon guidance in selected regions of the nervous system,
      including hippocampus, olfactory bulbs and cortex, as well as in neuronal cell
      cultures. In the present work, we have furthered our analysis of the role of KLF7
      in central nervous system development. By gene expression analysis during brain
      embryogenesis, we found significant alterations in dopaminergic neurons in Klf7
      null mice. In particular, the tyrosine hydroxylase (TH) and dopamine transporter
      (Dat) transcripts are strongly decreased in the olfactory bulbs and ventral
      midbrain at birth, compared to wild-type littermates. Interestingly, Klf7-mutant
      mice show a dramatic reduction of TH-positive neurons in the olfactory bulbs, but
      no change in GABAergic or midbrain dopaminergic neurons. These observations raise
      the possibility that a lack of a KLF family member affects dopaminergic neuron
      development.

PMID- 21093433
TI  - Molecular and cellular characterization of expanded and cryopreserved human
      limbal epithelial stem cells reveal unique immunological properties.
AB  - Transplantation of ex vivo expanded autologous limbal stem cells into the
      diseased eye of patients with limbal stem cell deficiency (LSCD) has been in
      practice worldwide. However, isolation of limbal tissue from the normal eye of
      the patient with unilateral LSCD still remains a major concern for the donor.
      More importantly, autologous cell transplantation is not a viable option for
      patients with bilateral LSCD. The objective of the current study was to determine
      the expansion potential of human limbal epithelial stem cells (hLESCs) for their
      possible use in allo-transplantation. A total of six limbal biopsy samples were
      cultured and expanded in vitro up to passage level 1 (P-1), at which point the
      hLESCs were cryopreserved. Semi-quantitative RT-PCR and immunophenotypic analysis
      revealed that hLESCs obtained before and after cryopreservation retained the
      expression of major limbal epithelial stem cell markers such as p63, SSEA-4,
      ABCG2, cytokeratin 19 (CK19), integrin beta1 and vimentin. One notable difference
      was that while P-0 hLESCs expressed HLA-DR mRNA, no HLA-DR gene expression was
      observed with the expanded and cryopreserved samples. Human LESCs did not express
      costimulatory proteins CD80 or B7-DC but expressed significant levels of CD86, B7
      H1 and HLA-ABC molecules on the cell surface. Treatment of hLESCs with IFN-gamma
      induced the expression of HLA-DR, indoleamine 2,3-dioxygenase (IDO) and HLA-G on
      these cells. Cultured hLESCs were unable to stimulate allogeneic T cell
      proliferation in vitro even in the presence of pro-inflammatory cytokine, IFN
      gamma. These results indicate that cryopreserved hLESCs are non-immunogenic in
      nature and express negative immunoregulatory molecules which may be critical for
      their survival in an allogeneic environment.

PMID- 21093434
TI  - Mechanism of aggregation of UV-irradiated beta(L)-crystallin.
AB  - Thermal denaturation and aggregation of UV-irradiated beta(L)-crystallin from eye
      lenses of steers have been studied. The data on size-exclusion chromatography and
      SDS-PAGE indicated that UV irradiation of beta(L)-crystallin at 10  degrees S
      resulted in fragmentation of the protein molecule and formation of cross-linked
      aggregates. Fluorescence data showed that tryptophan fluorescence in the
      irradiated protein decreased exponentially with the UV dose. Decrease in
      tryptophan fluorescence is a result of photochemical destruction, but not of
      conformational changes of protein, because there is no red shift in the
      fluorescence maximum. The differential scanning calorimetry (DSC) profiles of the
      samples of UV-irradiated and wild type beta(L)-crystallin were registered. The
      area under curves, which is proportional to the amount of the native protein,
      decreased exponentially with increasing the irradiation dose. The shape of the
      DSC profiles for the samples of UV-irradiated beta(L)-crystallin was identical to
      that for wild type beta(L)-crystallin. The DSC data allowed estimating the
      portion of UV-denatured beta(L)-crystallin, which is not registered by DSC, and
      the portion of the combined fraction consisting of native and UV-damaged
      molecules retaining the native structure. A conclusion has been made that UV
      induced denaturation of beta(L)-crystallin follows the one-hit model. The study
      of the kinetics of thermal aggregation of UV-irradiated beta(L)-crystallin at 37 
      degrees S using dynamic light scattering showed that the initial stage of
      aggregation was that of formation of the start aggregates with the hydrodynamic
      radius of 20 nm. Further sticking of the start aggregates proceeded in the regime
      of reaction-limited cluster-cluster aggregation. Splitting of the aggregate
      population into two components occurred above a definite point in time.

PMID- 21093435
TI  - TAT-mediated delivery of neuroglobin protects against focal cerebral ischemia in
      mice.
AB  - Neuroglobin (Ngb), a newly identified globin in vertebrate brain, has been
      suggested to be able to protect against brain hypoxic-ischemic injury. However,
      owing to its large size, the impermeability of the blood-brain barrier (BBB) to
      Ngb limits its application in brain injury. Recently, the 11-amino-acid human
      immunodeficiency virus trans-activator of transcription (TAT) protein
      transduction domain was shown to successfully deliver macromolecules into the
      brain. This study explored whether the TAT-Ngb fusion protein can cross the BBB
      and protect the brain from cerebral ischemia. The TAT-Ngb fusion protein
      generated from Escherichia coli BL21 (DE3) was efficiently delivered into mice
      brain tissues by intravenous injection as demonstrated by immunohistochemistry
      and Western blotting. Two groups of mice were treated with filamentous middle
      cerebral artery occlusion (MCAO) for 30min or 2h followed by reperfusion. Each
      group was then divided into sub-groups and was injected intravenously with TAT
      Ngb, Ngb, or saline respectively before MCAO or immediately after reperfusion.
      Compared with the Ngb- and saline-treated group, the group with TAT-Ngb treated
      2h before MCAO showed significantly less brain infarct volume and had better
      neurologic outcomes (p<0.05). Furthermore, a TAT-Ngb injection following a 30-min
      MCAO treatment significantly increased neuronal survival in the striatum
      (p<0.05). Our results demonstrated that the exogenous Ngb fusion protein
      containing the TAT protein transduction domain could be efficiently transduced
      into neurons in the mouse and protect the brain from mild or moderate ischemic
      injury.

PMID- 21093436
TI  - Neuroprotective and neurodegenerative effects of the chronic expression of tumor
      necrosis factor alpha in the nigrostriatal dopaminergic circuit of adult mice.
AB  - Tumor necrosis factor (TNF)-alpha, a pro-inflammatory cytokine, has been
      implicated in both neuronal death and survival in Parkinson's disease (PD). The
      substantia nigra (SN), a CNS region affected in PD, is particularly susceptible
      to inflammatory insults and possesses the highest density of microglial cells,
      but the effects of inflammation and in particular TNF-alpha on neuronal survival
      in this region remains controversial. Using adenoviral vectors, the CRE/loxP
      system and hypomorphic mice, we achieved chronic expression of two levels of TNF
      alpha in the SN of adult mice. Chronic low expression of TNF-alpha levels reduced
      the nigrostriatal neurodegeneration mediated by intrastriatal 6-hydroxydopamine
      administration. Protective effects of low TNF-alpha level could be mediated by
      TNF-R1, GDNF, and IGF-1 in the SN and SOD activity in the striatum (ST). On the
      contrary, chronic expression of high levels of TNF-alpha induced progressive
      neuronal loss (63% at 20 days and 75% at 100 days). This effect was accompanied
      by gliosis and an inflammatory infiltrate composed almost exclusively by
      monocytes/macrophages. The finding that chronic high TNF-alpha had a slow and
      progressive neurodegenerative effect in the SN provides an animal model of PD
      mediated by the chronic expression of a single cytokine. In addition, it supports
      the view that cytokines are not detrimental or beneficial by themselves, i.e.,
      their level and time of expression among other factors can determine its final
      effect on CNS damage or protection. These data support the view that new anti
      parkinsonian treatments based on anti-inflammatory therapies should consider
      these dual effects of cytokines on their design.

PMID- 21093437
TI  - Potassium channel blocker, 4-aminopyridine-3-methanol, restores axonal conduction
      in spinal cord of an animal model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a severely debilitating neurodegenerative diseases
      marked by progressive demyelination and axonal degeneration in the CNS. Although
      inflammation is the major pathology of MS, the mechanism by which it occurs is
      not completely clear. The primary symptoms of MS are movement difficulties caused
      by conduction block resulting from the demyelination of axons. The possible
      mechanism of functional loss is believed to be the exposure of potassium channels
      and increase of outward current leading to conduction failure. 4-Aminopyridine (4
      AP), a well-known potassium channel blocker, has been shown to enhance conduction
      in injured and demyelinated axons. However, 4-AP has a narrow therapeutic range
      in clinical application. Recently, we developed a new fast potassium channel
      blocker, 4-aminopyridine-3-methanol (4-AP-3-MeOH). This novel 4-AP derivative is
      capable of restoring impulse conduction in ex vivo injured spinal cord without
      compromising the ability of axons to follow multiple stimuli. In the current
      study, we investigated whether 4-AP-3-MeOH can enhance impulse conduction in an
      animal model of MS. Our results showed that 4-AP-3-MeOH can significantly
      increase axonal conduction in ex vivo experimental autoimmune encephalomyelitis
      mouse spinal cord.

PMID- 21093438
TI  - Cortical hyperexcitability in response to preserved spinothalamic inputs
      immediately after spinal cord hemisection.
AB  - Chronic injury of the main somatosensory pathways ascending along the spinal cord
      - the dorsal columns and the spinothalamic tract - can produce both changes in
      the organization of cortical somatotopic maps and neuropathic pain. Little is
      known, however, about the early neurophysiological changes occurring immediately
      after injury. We bilaterally recorded the neural activity of the hindpaw
      representation of the primary somatosensory cortex evoked by stimuli delivered to
      the hindpaws before and immediately after a thoracic spinal cord hemisection in
      anesthetized rats. This unilateral spinal cord injury allowed us to separately
      investigate the cortical effects of deafferenting the dorsal column (stimuli
      ipsilateral to the hemisection) or the spinothalamic tract (stimuli contralateral
      to the hemisection). The hemisection produced immediate bilateral changes in the
      cortical responses evoked by stimuli delivered to the hindpaw ipsilateral to the
      hemisection (deafferented dorsal column): an expected loss of classical short
      latency cortical responses, accompanied by an unexpected appearance of long
      latency activations. At the population level, these activations reflected a
      progressive stimulus-induced transition of the hindpaw somatosensory cortex from
      up-and-down states to a sustained activated state. At the single-cell level,
      these cortical activations resembled the "wind-up" typically observed - with the
      same type of stimuli - in the dorsal horn cells originating the spinothalamic
      tract. Virtually no changes were observed in the responses evoked by stimuli
      delivered to the hindpaw contralateral to the hemisection (deafferented
      spinothalamic tract). These results suggest that spinal cord hemisection
      immediately produces an abnormal hyperexcitability of the primary somatosensory
      cortex in response to preserved spinothalamic inputs from the hindpaw. This
      immediate cortical hyperexcitability could be important to understand the long
      term development of cortical reorganization and neuropathic pain after incomplete
      spinal cord lesions.

PMID- 21093439
TI  - Reactivation of viral hepatitis in immunosuppressed patients: an ounce of
      prevention is worth a pound of cure.

PMID- 21093440
TI  - Eimeria papillata: upregulation of specific miRNA-species in the mouse jejunum.
AB  - Increasing evidence indicates miRNAs as critical regulators of gene expression,
      but little information is available for miRNAs in intestinal diseases. Here, we
      investigated intestinal infections of male Balb/c mice with the coccidian
      parasite Eimeria papillata. On day 4 after oral infection, mice were shedding
      3150 +/- 430 oocysts per gram feces. This was associated with a low inflammatory
      response of the jejunum of mice evidenced by histology, non-response of IL-1beta
      mRNA, even slight downregulation of IL-6 mRNA, only slight increases in iNOS
      mRNA, nitrate/nitrate, malondialdehyde, and a small decrease in glutathione,
      respectively. Only IFNgamma mRNA was strongly induced. Using miRNA microarray
      technology, there were significantly upregulated the four miRNA species miR-1959,
      MCMV-miR-M23-1-5P, miR-203, and miR-21 out of 634 miRNAs, which was also
      confirmed by quantitative RT-PCR. Our data provide evidence that E. papillata
      parasites are able to induce specific miRNA species in their host target organ.

PMID- 21093441
TI  - Helicobacter pylori chromosomal DNA replication: current status and future
      perspectives.
AB  - Helicobacter pylori causes gastritis, gastric ulcer and gastric cancer. Though
      DNA replication and its control are central to bacterial proliferation,
      pathogenesis, virulence and/or dormancy, our knowledge of DNA synthesis in slow
      growing pathogenic bacteria like H. pylori is still preliminary. Here, we review
      the current understanding of DNA replication, replication restart and
      recombinational repair in H. pylori. Several differences have been identified
      between the H. pylori and Escherichia coli replication machineries including the
      absence of DnaC, the helicase loader usually conserved in gram-negative bacteria.
      These differences suggest different mechanisms of DNA replication at initiation
      and restart of stalled forks in H. pylori.

PMID- 21093442
TI  - Structural basis of CX-4945 binding to human protein kinase CK2.
AB  - Protein kinase CK2 (CK2), a constitutively active serine/threonine kinase, is
      involved in a variety of roles essential to the maintenance of cellular
      homeostasis. Elevated levels of CK2 expression results in the dysregulation of
      key signaling pathways that regulate transcription, and has been implicated in
      cancer. The adenosine-5'-triphosphate-competitive inhibitor CX-4945 has been
      reported to show broad spectrum anti-proliferative activity in multiple cancer
      cell lines. Although the enzymatic IC(50) of CX-4945 has been reported, the
      thermodynamics and structural basis of binding to CK2alpha remained elusive.
      Presented here are the crystal structures of human CK2alpha in complex with CX
      4945 and adenylyl phosphoramidate at 2.7 and 1.3 A, respectively. Biophysical
      analysis of CX-4945 binding is also described. This data provides the structural
      rationale for the design of more potent inhibitors against this emerging cancer
      target.

PMID- 21093443
TI  - Profiles in comparative endocrinology: Glen Van Der Kraak.

PMID- 21093444
TI  - An animal model of eating disorders associated with stressful experience in early
      life.
AB  - Experience of childhood abuse is prevalent among patients with eating disorders,
      and dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in
      its pathophysiology. Neonatal maternal separation is considered as an animal
      model of stressful experience early in life. Many of studies have demonstrated
      its impact both on the activity of HPA axis and the development of psycho
      emotional disorders later in life. In this paper, a series of our researches on
      developing an animal model of eating disorders is reviewed. An animal model of
      neonatal maternal separation was used; Sprague-Dawley pups were separated from
      dam daily for 180 min during the first 2 weeks of life (MS) or undisturbed.
      Anxiety-/depression-like behaviors were observed in MS rats at the age of two
      months with decreased serotonergic activity in the hippocampus and the raphe.
      Post-weaning social isolation promoted food intake and weight gain of adolescent
      MS pups, with impacts on anxiety-like behaviors. Sustained hyperphagia was
      observed in the MS pups subjected to a fasting/refeeding cycle repeatedly during
      adolescence, with increased plasma corticosterone levels. Anhedonia, major
      symptom of depression, to palatable food was observed in adolescent MS pups with
      blunted response of the mesolimbic dopaminergic activity to stress. Results
      suggest that neonatal maternal separation lead to the development of eating
      disorders when it is challenged with social or metabolic stressors later in life,
      in which dysfunctions in the HPA axis and the brain monoaminergic systems may
      play important roles.

PMID- 21093445
TI  - Development of a multiplex microsphere immunoassay for the quantitation of
      salivary antibody responses to selected waterborne pathogens.
AB  - Saliva has an important advantage over serum as a medium for antibody detection
      due to non-invasive sampling, which is critical for community-based
      epidemiological surveys. The development of a Luminex multiplex immunoassay for
      measurement of salivary IgG and IgA responses to potentially waterborne
      pathogens, Helicobacter pylori, Toxoplasma gondii, Cryptosporidium, and four
      noroviruses, involved selection of antigens and optimization of antigen coupling
      to Luminex microspheres. Coupling confirmation was conducted using antigen
      specific antibody or control sera at serial dilutions. Dose-response curves
      corresponding to different coupling conditions were compared using statistical
      tests. Control proteins in the specific antibody assay and a separate duplex
      assay for total immunoglobulins G and A were employed to assess antibody cross
      reactivity and variability in saliva composition. 200 saliva samples
      prospectively collected from 20 adult volunteers and 10 paired sera from a subset
      of these volunteers were used to test this method. For chronic infections, H.
      pylori and T. gondii, individuals who tested IgG seropositive using commercial
      diagnostic ELISA also had the strongest salivary antibody responses in salivary
      antibody tests. A steep increase in anti-norovirus salivary antibody response
      (immunoconversion) was observed after an episode of acute diarrhea and vomiting
      in a volunteer. The Luminex assay also detected seroconversions to
      Cryptosporidium using control sera from infected children. Ongoing efforts
      involve further verification of salivary antibody tests and their application in
      larger pilot community studies.

PMID- 21093446
TI  - Expression of recombinant human interleukin-8 and its purification using a single
      buffer system.
AB  - Chemokines, a class of small secreted proteins, direct immune cells to their
      target sites and play an important role in chronic inflammations and allergies.
      To study their interactions with their cellular receptors or potential inhibitors
      large quantities of chemokines are required. Here we present a fast and efficient
      strategy to purify the human chemokine interleukin-8 (IL-8, CXCL8). The chemokine
      is expressed with a pelB-leader peptide that is cleaved off its N-terminus by an
      endogenous bacterial peptidase. This yields wild-type 72aa IL-8 with a serine at
      its N-terminus. IL-8 is recovered in the soluble fraction after lysis while pelB
      IL8 fusion protein remains in the pellet. Interleukin-8 is purified via cation
      exchange chromatography and heparin affinity chromatography using a single
      inexpensive buffer system. No dialysis or membrane filtration steps are required
      and the final protein fractions may be used without any desalting steps. The use
      of 0.5% Triton X-114 in the lysis buffer leads to low endotoxin levels in the
      resulting protein. The protein can be eluted from the gel filtration column with
      a variety of buffers and is ready to be used in binding assays and activity
      assays.

PMID- 21093447
TI  - Construction of divalent anti-keratin 8 single-chain antibodies (sc(Fv)(2)),
      expression in Pichia pastoris and their reactivity with multicellular tumor
      spheroids.
AB  - Single-chain variable fragments (scFvs) are small monovalent recombinant antibody
      fragments that retain the specificity of their parent immunoglobulins. ScFvs are
      excellent building blocks for new and improved immunodiagnostic and therapeutic
      proteins. However, the monovalency and the rapid renal elimination of scFvs
      result in poor tumor accumulation and retention. Engineering divalent antibody
      fragments is an excellent way to address these shortcomings. In this study,
      covalent divalent single-chain variable fragments (sc(Fv)(2)s), were constructed
      from the monovalent anti-keratin 8 scFvs, TS1-218 and its mutant, HE1-Q. The
      scFvs and sc(Fv)(2)s were expressed in the methylotrophic yeast Pichia pastoris,
      utilizing the alpha-factor secretion signal (alpha-factor) for extracellular
      secretion. The immunoreactivity and specificity of the antibody fragments were
      analyzed with enzyme-linked immunosorbent assay (ELISA) and the uptake and
      retention of the (125)I labeled antibody fragments were evaluated using HeLa HEp
      2 multicellular tumor spheroids (MCTSs). Analysis of the antibody fragments
      demonstrated that parts of the alpha-factor remained at the N-terminal of the
      antibody fragments. Despite incomplete processing of the alpha-factor, the
      antibody fragments were functional where the sc(Fv)(2)s gave a three-fold
      stronger signal in ELISA compared to their scFv counterparts and the mutant
      antibodies demonstrated a stronger signal than their initial wild types. In
      addition, the sc(Fv)(2)s DiTS1-218 and DiHE1-Q displayed an approximately two
      fold higher uptake and were retained to a larger extent in the MCTS,
      demonstrating a 3.9 and 9.4-fold increase in half-life respectively compared to
      their corresponding scFvs. In conclusion, expression in P. pastoris improved the
      yield 20-fold and facilitated the purification of the antibody fragments.
      Furthermore, the sc(Fv)(2)s presented a higher functional affinity to K 8 both in
      ELISA and MCTS compared to the scFvs with DiHE1-Q being the best candidate for
      further studies.

PMID- 21093448
TI  - Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell
      vaccine.
AB  - In the search for a therapeutic HIV-1 vaccine, we describe herein the development
      of a monocyte-derived dendritic cell (DC) vaccine loaded with a mixture of HIV-1
      antigen lipopeptides (ANRS HIV-LIPO-5 Vaccine). LIPO-5 is comprised of five HIV-1
      antigen peptides (Gag(17-35), Gag(253-284), Nef(66-97), Nef(116-145), and Pol(325
      355)), each covalently linked to a palmitoyl-lysylamide moiety. Monocytes
      enriched from HIV-1-infected highly active antiretroviral therapy (HAART)-treated
      patients were cultured for three days with granulocyte-macrophage colony
      stimulating factor and alpha-interferon. At day 2, the DCs were loaded with ANRS
      HIV-LIPO-5 vaccine, activated with lipopolysaccharide, harvested at day 3 and
      frozen. Flow cytometry analysis of thawed DC vaccines showed expression of DC
      differentiation markers: CD1b/c, CD14, HLA-DR, CD11c, co-stimulatory molecule
      CD80 and DC maturation marker CD83. DCs were capable of eliciting an HIV-1
      antigen-specific response, as measured by expansion of autologous CD4(+) and
      CD8(+) T-cells. The expanded T-cells secreted gamma-IFN and interleukin (IL)-13,
      but not IL-10. The safety and immunogenicity of this DC vaccine are being
      evaluated in a Phase I/II clinical trial in chronically HIV-1-infected patients
      on HAART (clinicaltrials.gov identifier: NCT00796770).

PMID- 21093449
TI  - Towards nano-physiology of insects with atomic force microscopy.
AB  - Little study of insects with modern nanotechnology tools has been done so far.
      Here we use one of such tool, atomic force microscopy (AFM) to study surface
      oscillations of the ladybird beetles (Hippodamia convergens) measured in
      different parts of the insect at picometer level. This allows us to record a much
      broader spectral range of possible surface vibrations (up to several kHz) than
      the previously studied oscillations due to breathing, heartbeat cycles,
      coelopulses, etc. (up to 5-10Hz). Here we demonstrate three different ways with
      which one can identify the origins of the observed peaks - by physical
      positioning the probe near a specific organ, and by using biological or chemical
      stimuli. We report on identification of high frequency peaks associated with H.
      convergens heart, spiracular closer muscles, and oscillations associated with
      muscles activated while drinking. The method, being a relatively non-invasive
      technique providing a new type of information, may be useful in developing
      "nanophysiology" of insects.

PMID- 21093450
TI  - Myogenic nature of insect heartbeat and intestinal peristalsis, revealed by
      neuromuscular paralysis caused by the sting of a braconid wasp.
AB  - Larvae of the greater waxmoth (Galleria mellonella) become paralysed by the venom
      of the braconid wasp (Habrobracon hebetor) a few minutes after intoxication. The
      profound neuromuscular paralysis, which may last for several weeks, includes all
      somatic muscles that are innervated through neuromuscular transmission. The
      peristaltic contractions of the heart and intestine, which are regulated by the
      depolarisation potentials of the myocardium or intestinal epithelial muscles,
      remain unaffected and fully functional. Heartbeat patterns and intestinal
      pulsations were monitored in the motionless, paralysed larvae by means of
      advanced electrocardiographic recording methods (contact thermography, pulse
      light optocardiography). The records revealed more or less constant cardiac
      pulsations characterised by 20-25 systolic contractions per minute. The
      contractions were peristaltically propagated in the forward (anterograde)
      direction, with a more or less constant speed of 10mm per second (23-25 degrees
      C). Additional electrocardiographic investigations on larvae immobilised by
      decapitation revealed the autonomic (brain independent) nature of heartbeat
      regulation. Sectioning performed in the middle of the heart (4th abdominal
      segment) seriously impaired the pacemaker rhythmicity and slowed down the rate of
      heartbeat in the anterior sections. By contrast, the functions of the posterior
      compartments of the disconnected heart remained unaffected. These results
      confirmed our previous conclusions about the existence of an autonomic, myogenic,
      pacemaker nodus in the terminal part of an insect heart. They show an analogy to
      the similar myogenic, sinoatrial or atrioventricular nodi regulating rhythmicity
      of the human heart. Peristaltic contractions of the intestine also represent a
      purely myogenic system, which is fully functional in larvae with complete
      neuromuscular paralysis. Unlike the constant anterograde direction of the
      heartbeat, intestinal peristaltic waves periodically reversed anterograde and
      retrograde directions. A possibility that the functional similarity between
      insect and human hearts may open new avenues in the field of comparative
      cardiology has been discussed.

PMID- 21093452
TI  - The structure of the CRISPR-associated protein Csa3 provides insight into the
      regulation of the CRISPR/Cas system.
AB  - Adaptive immune systems have recently been recognized in prokaryotic organisms
      where, in response to viral infection, they incorporate short fragments of
      invader-derived DNA into loci called clustered regularly interspaced short
      palindromic repeats (CRISPRs). In subsequent infections, the CRISPR loci are
      transcribed and processed into guide sequences for the neutralization of the
      invading RNA or DNA. The CRISPR-associated protein machinery (Cas) lies at the
      heart of this process, yet many of the molecular details of the CRISPR/Cas system
      remain to be elucidated. Here, we report the first structure of Csa3, a CRISPR
      associated protein from Sulfolobus solfataricus (Sso1445), which reveals a
      dimeric two-domain protein. The N-terminal domain is a unique variation on the
      dinucleotide binding domain that orchestrates dimer formation. In addition, it
      utilizes two conserved sequence motifs [Thr-h-Gly-Phe-(Asn/Asp)-Glu-X(4)-Arg and
      Leu-X(2)-Gly-h-Arg] to construct a 2-fold symmetric pocket on the dimer axis.
      This pocket is likely to represent a regulatory ligand-binding site. The N
      terminal domain is fused to a C-terminal MarR-like winged helix-turn-helix domain
      that is expected to be involved in DNA recognition. Overall, the unique domain
      architecture of Csa3 suggests a transcriptional regulator under allosteric
      control of the N-terminal domain. Alternatively, Csa3 may function in a larger
      complex, with the conserved cleft participating in protein-protein or protein
      nucleic acid interactions. A similar N-terminal domain is also identified in
      Csx1, a second CRISPR-associated protein family of unknown function.

PMID- 21093451
TI  - Cardiac gene therapy with SERCA2a: from bench to bedside.
AB  - While progress in conventional treatments is making steady and incremental gains
      to reduce mortality associated with heart failure, there remains a need to
      explore potentially new therapeutic approaches. Heart failure induced by
      different etiologies such as coronary artery disease, hypertension, diabetes,
      infection, or inflammation results generally in calcium cycling dysregulation at
      the myocyte level. Recent advances in understanding of the molecular basis of
      these calcium cycling abnormalities, together with the evolution of increasingly
      efficient gene transfer technology, have placed heart failure within reach of
      gene-based therapy. Furthermore, the recent successful completion of a phase 2
      trial targeting the sarcoplasmic reticulum calcium pump (SERCA2a) ushers in a new
      era for gene therapy for the treatment of heart failure. This article is part of
      a Special Section entitled "Special Section: Cardiovascular Gene Therapy".

PMID- 21093453
TI  - A top-down linguistic approach to the analysis of genomic sequences: The
      metabotropic glutamate receptors 1 and 5 in human and in mouse as a case study.
AB  - This paper presents a top-down strategy to detect features in genomic sequences.
      The strategy's core is to exploit dictionary-based compression algorithms and
      analyse the content of the automatically generated dictionary. We classify the
      different over-represented segments and in the case study we correlate them to
      experimentally identified or theoretically forecasted biological features. A
      large spectrum analysis reveals that the only feature co-located with the a
      priori extracted segments is the torsional flexibility of DNA, while non-B DNA
      configurations are anti-localized and other features are mostly independent of
      the extracted sequences. This analysis unravels complex relationships between the
      linguistic structures investigated under our approach and some known biological
      features.

PMID- 21093454
TI  - In vitro and in silico binding study of the peptide derived from HIV-1 CA-CTD and
      LysRS as a potential HIV-1 blocking site.
AB  - The assembly process in HIV-1 has become a new target for infected HIV-1 patient
      treatment. During this process, the viral genomic RNA and precursor protein are
      assembled at the permeable membrane and tRNA(Lys3) is packed into a new virion as
      the primer for the reverse transcription process. The packaging of tRNA(Lys3)
      arises from the interaction of HIV-1 Gag and hLysRS. To better understand the
      formation of this ternary complex, the interaction study of LysRS-peptide complex
      using a combination of circular dichroism, molecular dockings and molecular
      dynamic simulations are reported here. The circular dichroism experiments confirm
      that the sh-H4 peptide, containing 10 amino acid residues from helix4 of C
      terminal domain of HIV-1 capsid protein (CA-CTD), can be induced to form a
      helical structure upon binding to hLysRS. Molecular docking analysis of LysRS
      (hLysRS and eLysRS) with the sh-H4 peptide revealed the two possible arrangements
      of the peptide upon the binding event. Molecular dynamics based free energy
      calculations of the peptide binding process are used to determine the
      interactions as well as the important amino acid residues involving in binding.
      The peptide is found to lie against helix 7 of LysRS in a perpendicular fashion.
      Additionally, the peptide preferably interacts with hLysRS over eLysRS including
      strong hydrogen bond interactions between R247-Q219 and R241-E212. Interestingly,
      these amino acid residues are found in both LysRS and CA-CTD. These important
      residues appear to be a vital feature of the LysRS-CA-CTD complex and may
      ultimately lead to the inhibitor design to block the Gag-LysRS interaction.

PMID- 21093455
TI  - Consequences of host heterogeneity, epitope immunodominance, and immune breadth
      for strain competition.
AB  - Consumer-resource dynamics of hosts with their pathogens are modulated by complex
      interactions between various branches of hosts' immune systems and the
      imperfectly perceived pathogen. Multistrain SIR models tend to sweep competitive
      interaction terms between different pathogen strains into a single parameter
      representing cross-immunity. After reviewing several hypotheses about the
      generation of immune responses, we look into the consequences of assuming that
      hosts with identical immune repertoires respond to new pathogens identically. In
      particular, we vary the breadth of the typical immune response, or the average
      number of pathogen epitopes a host perceives, and the probability of perceiving a
      particular epitope. The latter quantity in our model is equivalent both to the
      degree of diversity in host responses at the population level and the relative
      immunodominance of different epitopes. We find that a sharp transition to strain
      coexistence occurs as host responses become narrow or skewed toward one epitope.
      Increasing the breadth of the immune response and the immunogenicity of different
      epitopes typically increases the range of cross-immunity values in which chaotic
      strain dynamics and competitive exclusion occur. Models attempting to predict the
      outcomes of strain competition should thus consider the potential diversity and
      specificity of hosts' responses to infection.

PMID- 21093456
TI  - Perturbation analysis of 6DoF flight dynamics and passive dynamic stability of
      hovering fruit fly Drosophila melanogaster.
AB  - Insects exhibit exquisite control of their flapping flight, capable of performing
      precise stability and steering maneuverability. Here we develop an integrated
      computational model to investigate flight dynamics of insect hovering based on
      coupling the equations of 6 degree of freedom (6DoF) motion with the Navier
      Stokes (NS) equations. Unsteady aerodynamics is resolved by using a biology
      inspired dynamic flight simulator that integrates models of realistic wing-body
      morphology and kinematics, and a NS solver. We further develop a dynamic model to
      solve the rigid body equations of 6DoF motion by using a 4th-order Runge-Kutta
      method. In this model, instantaneous forces and moments based on the NS-solutions
      are represented in terms of Fourier series. With this model, we perform a
      systematic simulation-based analysis on the passive dynamic stability of a
      hovering fruit fly, Drosophila melanogaster, with a specific focus on responses
      of state variables to six one-directional perturbation conditions during latency
      period. Our results reveal that the flight dynamics of fruit fly hovering does
      not have a straightforward dynamic stability in a conventional sense that
      perturbations damp out in a manner of monotonous convergence. However, it is
      found to exist a transient interval containing an initial converging response
      observed for all the six perturbation variables and a terminal instability that
      at least one state variable subsequently tends to diverge after several wing beat
      cycles. Furthermore, our results illustrate that a fruit fly does have sufficient
      time to apply some active mediation to sustain a steady hovering before losing
      body attitudes.

PMID- 21093457
TI  - Ubiquitin ligase switch in plant photomorphogenesis: A hypothesis.
AB  - The E3 ubiquitin ligase COP1 (CONSTITUTIVE PHOTOMORPHOGENIC1) plays a key role in
      the repression of the plant photomorphogenic development in darkness. In the
      presence of light, COP1 is inactivated by a mechanism which is not completely
      understood. This leads to accumulation of COP1's target transcription factors,
      which initiates photomorphogenesis, resulting in dramatic changes of the
      seedling's physiology. Here we use a mathematical model to explore the possible
      mechanism of COP1 modulation upon dark/light transition in Arabidopsis thaliana
      based upon data for two COP1 target proteins: HY5 and HFR1, which play critical
      roles in photomorphogenesis. The main reactions in our model are the inactivation
      of COP1 by a proposed photoreceptor-related inhibitor I and interactions between
      COP1 and a CUL4 (CULLIN4)-based ligase. For building and verification of the
      model, we used the available published and our new data on the kinetics of HY5
      and HFR1 together with the data on COP1 abundance. HY5 has been shown to
      accumulate at a slower rate than HFR1. To describe the observed differences in
      the timecourses of the "slow" target HY5 and the "fast" target HFR1, we
      hypothesize a switch between the activities of COP1 and CUL4 ligases upon
      dark/light transition, with COP1 being active mostly in darkness and CUL4 in
      light. The model predicts a bi-phasic kinetics of COP1 activity upon the exposure
      of plants to light, with its restoration after the initial decline and the
      following slow depletion of the total COP1 content. CUL4 activity is predicted to
      increase in the presence of light. We propose that the ubiquitin ligase switch is
      important for the complex regulation of multiple transcription factors during
      plants development. In addition, this provides a new mechanism for sensing the
      duration of light period, which is important for seasonal changes in plant
      development.

PMID- 21093458
TI  - Developmental and circulatory profile of the diploic veins.
AB  - To examine the development of the diploic veins in the calvarium, FITC-dextran
      was injected into the tail vein. The total area of the diploic veins showed a
      continuous, age-dependent development. We also measured the red blood cell (RBC)
      velocities in the diploic veins using an in vivo imaging technique and revealed
      RBCs with a significantly high velocity and unidirectional characteristics at the
      entrance route. The route passed from the basal periosteum of the cranial bone
      via the dura mater and into the diploic veins. Our findings indicate the
      existence of communications between intra- and extra-cranial circulation.

PMID- 21093460
TI  - Allosteric modulators induce distinct movements at the GABA-binding site
      interface of the GABA-A receptor.
AB  - Benzodiazepines (BZDs) and barbiturates exert their CNS actions by binding to
      GABA-A receptors (GABARs). The structural mechanisms by which these drugs
      allosterically modulate GABAR function, to either enhance or inhibit GABA-gated
      current, are poorly understood. Here, we used the substituted cysteine
      accessibility method to examine and compare structural movements in the GABA
      binding site interface triggered by a BZD positive (flurazepam), zero
      (flumazenil) and negative (3-carbomethoxy-4-ethyl-6,7-dimethoxy-beta-carboline,
      DMCM) modulator as well as the barbiturate pentobarbital. Ten residues located
      throughout the GABA-binding site interface were individually mutated to cysteine.
      Wild-type and mutant alpha(1)beta(2)gamma(2) GABARs were expressed in Xenopus
      laevis oocytes and functionally characterized using two-electrode voltage clamp.
      We measured and compared the rates of modification of the introduced cysteines by
      sulfhydryl-reactive methanethiosulfonate (MTS) reagents in the absence and
      presence of BZD-site ligands and pentobarbital. Flurazepam and DMCM each
      accelerated the rate of reaction at alpha(1)R131C and slowed the rate of reaction
      at alpha(1)E122C, whereas flumazenil had no effect indicating that simple
      occupation of the BZD binding site is not sufficient to cause movements near
      these positions. Therefore, BZD-induced movements at these residues are likely
      associated with the ability of the BZD to modulate GABAR function (BZD efficacy).
      Low, modulating concentrations of pentobarbital accelerated the rate of reaction
      at alpha(1)S68C and beta(2)P206C, slowed the rate of reaction at alpha(1)E122C
      and had no effect at alpha(1)R131C. These findings indicate that pentobarbital
      and BZDs induce different movements in the receptor, providing evidence that the
      structural mechanisms underlying their allosteric modulation of GABAR function
      are distinct.

PMID- 21093459
TI  - Multiple forms of long-term synaptic plasticity at hippocampal mossy fiber
      synapses on interneurons.
AB  - The hippocampal mossy fiber (MF) pathway originates from the dentate gyrus
      granule cells and provides a powerful excitatory synaptic drive to neurons in the
      dentate gyrus hilus and area CA3. Much of the early work on the MF pathway
      focused on its electrophysiological properties, and ability to drive CA3
      pyramidal cell activity. Over the last ten years, however, a new focus on the
      synaptic interaction between granule cells and inhibitory interneurons has
      emerged. These data have revealed an immense heterogeneity of long-term
      plasticity at MF synapses on various interneuron targets. Interestingly, these
      studies also indicate that the mechanisms of MF long-term plasticity in some
      interneuron subtypes may be more similar to pyramidal cells than previously
      appreciated. In this review, we first define the synapse types at each of the
      interneuron targets based on the receptors present. We then describe the
      different forms of long-term plasticity observed, and the mechanisms underlying
      each form as they are currently understood. Finally we highlight various open
      questions surrounding MF long-term plasticity in interneurons, focusing
      specifically on the induction and maintenance of LTP, and what the functional
      impact of persistent changes in efficacy at MF-interneuron synapses might be on
      the emergent properties of the inhibitory network dynamics in area CA3. This
      article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

PMID- 21093462
TI  - Interneurons in the basolateral amygdala.
AB  - The amygdala is a temporal lobe structure that is the center of emotion
      processing in the mammalian brain. Recent interest in the amygdala arises from
      its role in processing fear and the relationship of fear to human anxiety. The
      amygdaloid complex is divided into a number of subnuclei that have extensive
      intra and extra nuclear connections. In this review we discuss recent findings on
      the physiology and plasticity of inputs to interneurons in the basolateral
      amygdala, the primary input station. These interneurons are a heterogeneous group
      of cells that can be separated on immunohistochemical and electrophysiological
      grounds. Glutamatergic inputs to these interneurons form diverse types of
      excitatory synapses. This diversity is manifest in both the subunit composition
      of the underlying NMDA receptors as well as their ability to show plasticity. We
      discuss these differences and their relationship to fear learning. This article
      is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

PMID- 21093461
TI  - An intrinsic GABAergic system in human lymphocytes.
AB  - gamma-amino butyric acid (GABA) is an ubiquitous neurotransmitter in the central
      nervous system and it is also present in non-neuronal cells. In this study we
      investigated the presence of neuronal components of the GABAergic system in
      lymphocytes and its functional significance. By using RT-PCR we detected mRNA
      expression of different components of the GABAergic system in resting and mitogen
      activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA;
      ii) VIAAT, the vesicular protein involved in GABA storage; iii) GABA transporters
      (GAT-1 and GAT-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) subunits
      that conform ionotropic GABA receptors. The presence of VIAAT protein in resting
      and activated cells was confirmed by immunocytochemistry. The functionality of
      GABA transporters was evaluated by measuring the uptake of radioactive GABA. The
      results show that [(3)H]GABA uptake is 5-fold higher in activated than in resting
      lymphocytes. To determine if GABA subunits assemble into functional channels, we
      performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a
      specific agonist of ionotropic GABA receptors, elicit macroscopic currents in
      about 10-15% of the cells. Finally, by using [(3)H]thymidine incorporation
      assays, we determined that the presence of agonists of GABA receptor during
      activation inhibits lymphocyte proliferation. Our results reveal that lymphocytes
      have a functional GABAergic system, similar to the neuronal one, which may
      operate as a modulator of T-cell activation. Pharmacological modulation of this
      system may provide new approaches for regulation of T-cell response.

PMID- 21093463
TI  - The grouping benefit in extinction: overcoming the temporal order bias.
AB  - Grouping between contra- and ipsilesional stimuli can alleviate the lateralised
      bias in spatial extinction (Gilchrist, Humphreys, & Riddoch, 1996; Ward,
      Goodrich, & Driver, 1994). In the current study we demonstrate for the first time
      that perceptual grouping can also modulate the spatio/temporal biases in temporal
      order judgements affecting the temporal as well as the spatial coding of stimuli.
      Perceived temporal order was assessed by presenting two coloured letter stimuli
      in either hemi-field temporally segregated by a range of onset-intervals. Items
      were either identical (grouping condition) or differed in both shape and colour
      (non-grouping condition). Observers were required to indicate which item appeared
      second. Patients with visual extinction had a bias against the contralesional
      item appearing first, but this was modulated by perceptual grouping. When both
      items were identical in shape and colour the temporal bias against reporting the
      contralesional item was reduced. The results suggest that grouping can alter the
      coding of temporal relations between stimuli.

PMID- 21093465
TI  - Hemispheric differences in attentional orienting by social cues.
AB  - Research points to a right hemisphere bias for processing social stimuli.
      Hemispheric specialization for attention shifts cued by social stimuli, however,
      has been rarely studied. We examined the capacity of each hemisphere to orient
      attention in response to social and nonsocial cues using a lateralized spatial
      cueing paradigm. We compared the up/down orienting effects of eye gaze cues,
      arrow cues, and peripheral cues (change in luminance). Results revealed similar
      cueing effects in each visual field for nonsocial cues, but asymmetric effects
      for social cues. At both short (150 ms) and long (950 ms) cue-target intervals,
      gaze cueing was significant in the LVF, but not in the RVF. Thus, there is a
      right hemisphere bias for attentional orienting cued by social stimuli, but not
      for attentional orienting cued by nonsocial stimuli. This supports a theory of a
      separate neural system for socially cued orienting of attention, as well as a
      theory of separate parallel and simultaneous neural systems for attention in the
      two cerebral hemispheres.

PMID- 21093466
TI  - The influence of visual saliency on fixation patterns in individuals with Autism
      Spectrum Disorders.
AB  - It is widely reported that individuals with Autism Spectrum Disorders (ASD)
      direct their attention in an atypical manner. When viewing complex scenes,
      typically developing individuals look at social aspects of scenes more rapidly
      than individuals with ASD. In the absence of a strong drive to extract social
      information, is something else capturing attention in these initial fixations,
      such as visually salient features? Twenty four high-functioning adolescents with
      ASD and 24 typically developing matched control participants viewed a series of
      indoor and outdoor scenes while their eye movements were tracked. Participants in
      both groups were more likely to fixate on salient regions in the first five
      fixations than later in viewing. Peak saliency at fixation occurred at fixation
      two for the typically developing participants but at fixation three for ASD
      participants. This difference was driven by typically developing participants
      looking at heads earlier than ASD participants--which are often visually salient.
      No differences between groups were observed for images in which the heads were
      not salient. We can therefore conclude that visual saliency impacts fixation
      location in a similar manner in individuals with ASD and those with typical
      development. It was found that social features in scenes (heads) captured
      attention much more than visually salient features, even in individuals with ASD.

PMID- 21093464
TI  - Speech perception, rapid temporal processing, and the left hemisphere: a case
      study of unilateral pure word deafness.
AB  - The mechanisms and functional anatomy underlying the early stages of speech
      perception are still not well understood. One way to investigate the cognitive
      and neural underpinnings of speech perception is by investigating patients with
      speech perception deficits but with preserved ability in other domains of
      language. One such case is reported here: patient NL shows highly impaired speech
      perception despite normal hearing ability and preserved semantic knowledge,
      speaking, and reading ability, and is thus classified as a case of pure word
      deafness (PWD). NL has a left temporoparietal lesion without right hemisphere
      damage and DTI imaging suggests that he has preserved cross-hemispheric
      connectivity, arguing against an account of PWD as a disconnection of left
      lateralized language areas from auditory input. Two experiments investigated
      whether NL's speech perception deficit could instead result from an underlying
      problem with rapid temporal processing. Experiment 1 showed that NL has
      particular difficulty discriminating sounds that differ in terms of rapid
      temporal changes, be they speech or non-speech sounds. Experiment 2 employed an
      intensive training program designed to improve rapid temporal processing in
      language impaired children (Fast ForWord; Scientific Learning Corporation,
      Oakland, CA) and found that NL was able to improve his ability to discriminate
      rapid temporal differences in non-speech sounds, but not in speech sounds.
      Overall, these data suggest that patients with unilateral PWD may, in fact, have
      a deficit in (left lateralized) temporal processing ability, however they also
      show that a rapid temporal processing deficit is, by itself, unable to account
      for this patient's speech perception deficit.

PMID- 21093467
TI  - The effects of hedonically acceptable red pepper doses on thermogenesis and
      appetite.
AB  - Previous studies suggest consumption of red pepper (RP) promotes negative energy
      balance. However, the RP dose provided in these studies (up to 10 g/meal) usually
      exceeded the amount preferred by the general population in the United States
      (mean=~1 g/meal). The objective of this study was to evaluate the effects of
      hedonically acceptable RP doses served at a single meal in healthy, lean
      individuals on thermogenesis and appetite. Twenty-five men and women (aged 23.0
      +/- 0.5 years, BMI 22.6 +/- 0.3 kg/m(2), 13 spicy food users and 12 non-users)
      participated in a randomized crossover trial during which they consumed a
      standardized quantity (1 g); their preferred quantity (regular spicy food users
      1.8 +/- 0.3 g/meal, non-users 0.3 +/- 0.1 g/meal); or no RP. Energy expenditure,
      core body and skin temperature, and appetite were measured. Postprandial energy
      expenditure and core body temperature were greater, and skin temperature was
      lower, after test loads with 1 g RP than no RP. Respiratory quotient was lower
      after the preferred RP dose was ingested orally, compared to in capsule form.
      These findings suggest that RP's effects on energy balance stem from a
      combination of metabolic and sensory inputs, and that oral exposure is necessary
      to achieve RP's maximum benefits. Energy intake was lower after test loads with 1
      g RP than no RP in non-users, but not in users. Preoccupation with food, and the
      desire to consume fatty, salty, and sweet foods were decreased more (or tended to
      be decreased more) in non-users than users after a 1 g RP test load, but did not
      vary after a test load with no RP. This suggests that individuals may become
      desensitized to the effects of RP with long-term spicy food intake.

PMID- 21093468
TI  - Steroid receptors and microRNAs: relationships revealed.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that serve as post-transcriptional
      regulators of gene expression. They work predominantly by binding to
      complementary sequences in target messenger RNA (mRNA) 3' untranslated regions
      (UTRs) where they prevent translation or cause degradation of the message.
      Steroid hormone receptors (SHRs) are ligand-activated transcription factors that
      regulate genes in steroid responsive tissues. Recent studies demonstrate that
      SHRs regulate miRNAs, and in turn, miRNAs can regulate SHR expression and
      function. Mounting evidence indicates that miRNAs are intimately involved with
      SHRs, as they are with other transcription factors, often in double negative
      feedback loops. Investigators are just beginning to expose the details of these
      complex relationships and reveal the extent to which miRNAs are involved with
      SHRs in normal physiology and the pathobiology of steroid hormone responsive
      tissues.

PMID- 21093469
TI  - Integration of contour and surface information in shape detection.
AB  - In studies of shape perception, the detection of contours and the segregation of
      regions enclosed by these contours have mostly been treated in isolation.
      However, contours and surfaces somehow need to be combined to create a stable
      perception of shape. In this study, we used a 2AFC task with arrays of oriented
      Gabor elements to determine whether and to what extent human observers integrate
      information from the contour and from the interior surface of a shape embedded in
      this array. The saliency of the shapes depended on the alignment of Gabors along
      the shape outline and on the isolinearity of Gabors inside the shape. In two
      experiments we measured detectability of shapes defined by the contour cue, by
      the surface cue, and by the combination of both cues. As a first step, we matched
      performance in the two single-cue conditions. We then compared shape
      detectability in the double-cue condition with the two equally detectable single
      cue conditions. Our results show a clear double-cue benefit: Participants used
      both cues to detect the shapes. Next, we compared performance in the double-cue
      condition with the performance predicted by two models of sensory cue
      combination: a minimum rule (probability summation) and an integration rule
      (information summation). Results from Experiment 2 indicate that participants
      applied a combination rule that was better than mere probability summation. We
      found no evidence against the integration rule.

PMID- 21093470
TI  - Knowing the future: partial foreknowledge effects on the programming of
      prosaccades and antisaccades.
AB  - Foreknowledge about the demands of an upcoming trial may be exploited to optimize
      behavioural responses. In the current study we systematically investigated the
      benefits of partial foreknowledge--that is, when some but not all aspects of a
      future trial are known in advance. For this we used an ocular motor paradigm with
      horizontal prosaccades and antisaccades. Predictable sequences were used to
      create three partial foreknowledge conditions: one with foreknowledge about the
      stimulus location only, one with foreknowledge about the task set only, and one
      with foreknowledge about the direction of the required response only. These were
      contrasted with a condition of no-foreknowledge and a condition of complete
      foreknowledge about all three parameters. The results showed that the three types
      of foreknowledge affected saccadic efficiency differently. While foreknowledge
      about stimulus-location had no effect on efficiency, task foreknowledge had some
      effect and response-foreknowledge was as effective as complete foreknowledge.
      Foreknowledge effects on switch costs followed a similar pattern in general, but
      were not specific for switching of the trial attribute for which foreknowledge
      was available. We conclude that partial foreknowledge has a differential effect
      on efficiency, most consistent with preparatory activation of a motor schema in
      advance of the stimulus, with consequent benefits for both switched and repeated
      trials.

PMID- 21093471
TI  - Differences between perception of human faces and body shapes: evidence from the
      composite illusion.
AB  - The present study aimed to investigate whether human body forms--like human faces
      -undergo holistic processing. Evidence for holistic face processing comes from
      the face composite effect: two identical top halves of a face are perceived as
      being different if they are presented with different bottom parts. This effect
      disappears if both bottom halves are shifted laterally (misaligned) or if the
      stimulus is rotated by 180 degrees . We investigated whether comparable composite
      effects are observed for human faces and human body forms. Matching of upright
      faces was more accurate and faster for misaligned compared to aligned
      presentations. By contrast, there were no processing differences between aligned
      and misaligned bodies. An inversion effect emerged, with better recognition
      performance for upright compared to inverted bodies but not faces. The present
      findings provide evidence for the assumption that holistic processing-
      investigated with the composite illusion--is not involved in the perception of
      human body forms.

PMID- 21093472
TI  - Vision out of the corner of the eye.
AB  - The margin of the temporal visual field lies more than 90 degrees  from the line
      of sight and is critical for detecting incoming threats and for balance and
      locomotive control. We show (i) contrast sensitivity beyond 70 degrees  is higher
      for moving stimuli than for stationary, and in the outermost region, only moving
      stimuli are visible; (ii) sensitivity is highest for motion in directions near
      the vertical and horizontal axes and is higher for forward than for backward
      directions; (iii) the former anisotropy arises early in the visual pathway; (iv)
      thresholds for discriminating direction are lowest for upward and downward
      motion.

PMID- 21093473
TI  - Genetic ablation of S6-kinase does not prevent processing of SREBP1.
AB  - The SREBP family of transcription factors regulates the expression of genes
      involved in fatty acid and cholesterol biosynthesis. The activation of SREBP
      transcription factors requires proteolytic cleavage of the inactive precursor and
      nuclear translocation of the mature form of the protein. It has been shown that
      nuclear accumulation of the mature form of SREBP1 is induced in response to
      activation of the serine/threonine kinase Akt, an important effector of the
      Ras/PI3-kinase signalling pathway. Activation of SREBP by Akt depends on the
      mammalian target of rapamycin complex 1 (mTORC1) but the exact mechanism of this
      activation remains unclear. We have investigated whether ablation of different
      signalling molecules downstream of mTORC1 affects expression of SREBP targets
      genes. We could show that inhibition of S6-kinases 1 and 2 expression using RNA
      interference did not block induction of expression of fatty acid synthase (FASN)
      or ATP-citrate lyase (ACLY) following activation of Akt in human retinal pigment
      epithelial cells. Furthermore, accumulation of mature SREBP1 was not inhibited
      after combined silencing of S6-kinases 1 and 2. Genetic ablation of both kinases
      also did not prevent the formation of mature SREBP1 in mouse embryonic
      fibroblasts. Taken together, these results suggest that S6-kinases 1 and 2 are
      dispensable for the induction of SREBP processing in the experimental systems
      used here.

PMID- 21093474
TI  - Temporal and functional analysis of DNA replicated in early S phase.
AB  - In summary, recently developed technologies have begun to draw back the curtain
      of mystery that obscures some of the basic mechanisms of DNA replication at
      multiple levels. Studies using extended DNA and chromatin fiber techniques have
      proven valuable for identifying the location of origins of replication at
      specific genomic sites and determining their temporal order of replication, for
      identifying and quantifying sites of DNA damage and localizing chromatin proteins
      in relation to sites of DNA replication. The future potential of these methods
      include further discoveries in functional genomics and contributions to the
      elucidation of the histone code. Such studies could prove very valuable in
      studies of the mechanisms of cancer development, aging, and other processes of
      disordered genomic functioning.

PMID- 21093475
TI  - Pharmacological interaction between oxcarbazepine and two COX inhibitors in a rat
      model of inflammatory hyperalgesia.
AB  - Oxcarbazepine, ibuprofen and etodolac have efficacy in inflammatory pain. The
      combination of different drugs activates both central and peripheral pain
      inhibitory pathways to induce additive or synergistic antinociception, and this
      interaction may allow lower doses of each drug combined and improve the safety
      profile, with lower side-effects. This study aimed to examine the effects of
      oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations, in a rat model
      of inflammatory hyperalgesia, and determine the type of interaction between
      drugs. Rats were intraplantarly injected with carrageenan (0.1 ml, 1%) and the
      hyperalgesia was assessed by modified paw pressure test. The anti-hyperalgesic
      effects of oxcarbazepine, ibuprofen and etodolac and oxcarbazepine-ibuprofen and
      oxcarbazepine-etodolac combinations were examined. Drugs were co-administered in
      a fixed-dose fractions of the ED50 and the type of interaction was determined by
      isobolographic analysis. Oxcarbazepine (40-160 mg/kg; p.o.), ibuprofen (10-120
      mg/kg; p.o.) and etodolac (5-20 mg/kg; p.o.) produced a significant, dose
      dependent anti-hyperalgesia in carrageenan-injected rats. ED50 values (mean+/
      SEM) for oxcarbazepine, ibuprofen and etodolac were 88.17+/-3.65, 47.07+/-10.27
      and 13.05+/-1.42 mg/kg, respectively. Oxcarbazepine-ibuprofen and oxcarbazepine
      etodolac combinations induced significant and dose-dependent anti-hyperalgesia.
      Isobolographic analysis revealed that oxcarbazepine exerts a synergistic
      interaction with ibuprofen, with almost 4-fold reduction of doses of both drugs
      in combination. In contrast, there was an additive interaction with etodolac.
      Synergistic interaction of oxcarbazepine with ibuprofen and its additive
      interaction with etodolac provide new information about the combination pain
      treatment and could be explored further in patients with inflammatory pain.
      Adverse effect analysis of the combinations is necessary to verify possible
      clinical use of the mixtures.

PMID- 21093476
TI  - Synthesis and solution behavior of poly(epsilon-caprolactone) grafted
      hydroxyethyl cellulose copolymers.
AB  - Trimethylsilylated hydroxyethyl cellulose (TMSHEC) was synthesized by using
      hexamethyldisilazane (HMDS) as silylated agent. With the partial protection of
      hydroxyl groups of HEC by silylation, the novel poly(E-polycaprolactone) (PCL)
      grafted HEC (HEC-g-PCL) copolymers were successfully prepared by homogenous ring
      opening graft polymerization and deprotection procedure. The structure of HEC-g
      PCL copolymers was characterized by FTIR and 1H NMR. Fluorescence spectrum of HEC
      g-PCL copolymer dilute solution indicated that copolymers could associate and
      form hydrophobic microdomains in aqueous solution. With the increasing of grafted
      PCL content, the critical association concentration (cac) of HEC-g-PCL copolymers
      decreased. The surface tension of HEC-g-PCL copolymers decreased dramatically
      with the increasing of the concentration and then approached to a plateau value
      when concentration was above the cac of HEC-g-PCL copolymers. The hydrodynamic
      radius of the aggregate of copolymer in dilute solution was found to increase
      with the increasing of the grafted PCL content. When the concentration of
      copolymer was above the cac, the zero-shear viscosity of the copolymer increased
      sharply and became much higher than that of HEC at the same concentration.

PMID- 21093477
TI  - Linoleic acid-grafted chitosan oligosaccharide micelles for intracellular drug
      delivery and reverse drug resistance of tumor cells.
AB  - Intracellular drug delivery is an important rout to reverse drug resistance of
      tumor cells. In this study, the linoleic acid (LA)-grafted chitosan
      oligosaccharide (CSO) was synthesized to construct a micellar delivery system for
      intracellular delivery. The synthesized linoleic acid-grafted chitosan
      oligosaccharide (CSO-LA) with 10.3% graft ratio of LA could form micelles in
      aqueous with 86.69 MUg/ml critical micellar concentration (CMC). The CSO-LA
      micelle had 46.2+/-3.6 nm number average diameter and 36.0+/-3.3 mV zeta
      potential. Taking doxorubicin base (DOX) as a model drug, the drug-loaded CSO-LA
      micelles (CSO-LA/DOX) was then prepared. The drug encapsulation efficiencies of
      CSO-LA/DOX were as high as 80%, and the drug loading capacity could be improved
      by increasing the charged DOX. Using MCF-7, Doxorubicin.HCl resistant MCF-7 (MCF
      7/ADR), K562 and Doxorubicin.HCl resistant K562 (K562/ADR) cells as model drug
      sensitive and drug resistant tumor cells, the experiments demonstrated the CSO-LA
      had excellent cellular uptake ability by either drug sensitive tumor cells or
      drug resistance tumor cells. The CSO-LA micelles could deliver DOX into tumor
      cells, and the DOX in cells was increased with incubation time. As a result, the
      cytotoxicities of DOX encapsulated in CSO-LA micelles against drug resistance
      tumor cells were improved significantly, comparing to that of Doxorubicin.HCl
      solution.

PMID- 21093478
TI  - Molecular responses of calreticulin genes to iron overload and bacterial
      challenge in channel catfish (Ictalurus punctatus).
AB  - Infection and inflammation are often accompanied by oxidative stress caused by
      the accumulation of reactive oxygen species which can be deleterious to the
      health of the host. Antioxidant defense mechanisms and components are crucial in
      limiting cellular and tissue-level damage and restoring homeostasis. In mammals,
      calreticulin is a 46-kDa multifunctional calcium binding protein of the
      endoplasmic reticulum that has many critical functions in the eukaryotic cell
      including regulation of intracellular calcium homoeostasis, lectin binding and
      chaperoning, and oxidative stress responses. In previous studies from our lab,
      the calreticulin gene was observed to be strongly upregulated in catfish during
      challenge with infectious Gram-negative bacteria. However, little is known about
      the function of this gene in teleost fish. The objective of this study,
      therefore, was to characterize the calreticulin gene from channel catfish, to
      determine its genomic organization, to profile its patterns of tissue expression,
      and to establish its potential for physiological antioxidant and immune responses
      in catfish after bacterial infection with Edwardsiella ictaluri and iron
      treatment. Our results indicate that there are at least three calreticulin
      related genes in the catfish genome. The three calreticulin genes are widely
      expressed in various tissues under homeostatic conditions and their expression
      showed significant upregulation following infection and/or iron level changes.

PMID- 21093479
TI  - Topographical distribution of antimicrobial genes in the zebrafish intestine.
AB  - The zebrafish is increasingly being utilized to study aspects of the conserved
      innate intestinal immunity of vertebrates. In mammals, some antimicrobial
      proteins are synthesised by specialised immune cells that appear to have no
      equivalent in zebrafish. To delineate foci of antimicrobial protein production
      along the zebrafish intestine, we examined the antero-posterior expression
      gradients of antimicrobial genes. Quantitative PCR revealed distinct expression
      gradient profiles, with the mid-intestine exhibiting elevated expression of
      several genes such as dual oxidase and the defensin beta-like and peptidoglycan
      recognition protein families. This region also presented with the most numbers of
      leukocytes and endocytic cells, supporting a specialised immunological role.
      Conversely, expression of the Dr-RNase family was prominent in the anterior
      intestine. Expression of the zebrafish beta-defensin family was examined in adult
      zebrafish tissues. Strong expression of defensin beta-like 1 was detected in the
      swim bladder of zebrafish from the larval stage of development through to adults.

PMID- 21093480
TI  - Autism and ADHD: how far have we come in the comorbidity debate?
AB  - The potential for the coexistence of the developmental disorders autism and
      attention-deficit/hyperactivity disorder (ADHD) in any one individual has for a
      long time been a contentious issue. While from a neurobiological perspective it
      is possible, and even highly likely, that ADHD and autism might clinically co
      exist, our major diagnostic classification systems (DSM-IV-TR and ICD-10)
      currently preclude such a dual-diagnosis. The aim of the current review is to
      summarise current diagnostic criteria and treatment strategies for the two
      disorders, relevant theories of developmental dysfunction, and update the state
      of the debate regarding comorbidity. Evidence from clinical, neuroimaging and
      neuropsychological domains is considered, and similarities and differences
      between the two disorders are identified. Suggestions for future research into
      the comorbid profiles of these disorders are proposed, with a strong emphasis
      placed on the neuropsychological assessment of executive functioning as a
      potentially useful tool for both identifying similarities, and differentiating
      the disorders.

PMID- 21093481
TI  - Blood lead levels in relation to cognitive function in older U.S. adults.
AB  - Studies suggest that cumulative exposure to lead, as measured in the bone, is
      associated with accelerated cognitive decline at older age. It is presently
      unclear, however, whether current blood lead levels (BLLs) are adversely related
      to cognitive functioning in older adults. We evaluated BLLs in relation to
      cognition in the continuous National Health and Nutrition Examination Survey
      (NHANES). The current study was limited to adults age 60 and older. We examined
      two measures of cognitive functioning: self-reported functional limitation due to
      difficulty remembering or periods of confusion (NHANES 1999-2008; n=7277) and
      performance on the Digit Symbol Substitution Test (DSST; NHANES 1999-2002;
      n=2299). We evaluated quintiles of BLL (<1.30, 1.79-<2.30, 2.30-<3.20, and
      >=3.20MUg/dL) in relation to cognitive functioning using logistic (functional
      limitation) and linear (DSST scores) regression in SUDAAN, adjusting for age,
      sex, race, poverty-income ratio, education, and self-reported general health
      status. BLLs were not associated with self-reported confusion or memory problems
      in crude and adjusted analyses, with adjusted odds ratios and 95% confidence
      intervals (CI) of 1.0 (ref.), 0.9 (CI=0.7-1.3), 0.8 (CI=0.6-1.2), 1.0 (CI=0.7
      1.3), 1.0 (CI=0.7-1.4), respectively, in increasing quintiles. Similarly, there
      was no clear association between performance on the DSST and BLL after accounting
      for all covariates. Our findings add to the inconsistent evidence regarding the
      association between concurrent BLLs and cognitive function in older adults. Early
      life or long-term, accumulated lead exposures may be etiologically more relevant
      to accelerated cognitive decline at older age.

PMID- 21093483
TI  - Editorial HLDA9 special issue.

PMID- 21093482
TI  - A visual, position-independent instrumental reinforcer devaluation task for rats.
AB  - Flexible goal-directed behavior has been studied across species using reinforcer
      devaluation tasks, in which subjects form associations between specific stimuli
      (cues) and specific reinforcer(s). The reinforcer is subsequently devalued by
      selective satiation or taste aversion. Following devaluation, subjects adjust
      their responding to the cues reflecting the new value of the reinforcer. Tasks
      currently used in rats differ in several ways from tasks used in monkeys and this
      may explain contrasting results between the two species. To address one of the
      differences, we developed a rat task independent of spatial cues. It employs two
      visual cues presented simultaneously, changing left and right positions
      pseudorandomly. Each cue predicts one of two food reinforcers. Rats were trained
      to lever press in response to the two visual cues. Subsequently, they were
      satiated on one of the foods followed by an extinction test where in each trial
      they could choose to respond to one of the two cues, one predicting the devalued
      reinforcer and the other the non-devalued. This procedure was repeated later with
      the alternative food devalued. The rats adjusted their responding by choosing the
      cue predicting the devalued food significantly less (p<0.05) than the alternative
      cue. These results show that rats can discriminate two visual stimuli presented
      simultaneously, devalue two different foods by selective satiation, and transfer
      the new value to the visual cues. Discrimination of the visual cues is not aided
      by spatial cues, thereby eliminating a major difference between the instrumental
      tasks used in rats and the task used in monkeys.

PMID- 21093484
TI  - Development and field evaluation of a nested RT-PCR kit for detecting Japanese
      encephalitis virus in mosquitoes.
AB  - A novel nested reverse transcription-polymerase chain reaction (RT-PCR)-based kit
      is described for detecting Japanese encephalitis virus (JEV), especially for
      genotype 1 and 3 strains. The assay consists of a first round RT-PCR and a
      subsequent nested PCR amplification. It has unique features such as the use of a
      premix system in which all reagents are lyophilized in reaction tubes and the
      inclusion of control RNA in each reaction to monitor false negative results. In
      addition, an automatic tissue homogenizer and a RNA extraction system are used
      concurrently for assay standardization and increasing throughput. The assay using
      the kit proved specific for JEV with no amplification of other JEV-related
      flaviviruses. The detection limits were approximately 0.1 PFU/ml and 1 PFU/ml for
      JEV genotypes 1 and 3, respectively. The assay protocol has been validated in
      large-scale field trials in South Korea during the 2008-2009 surveillance
      seasons. Nineteen of 1136 pools of mosquitoes (54,583 mosquitoes total) were
      identified as JEV positive. This nested RT-PCR kit combined with control RNA and
      an automatic RNA extraction system should be suitable for routine JEV
      surveillance programs.

PMID- 21093485
TI  - Detection of all known filovirus species by reverse transcription-polymerase
      chain reaction using a primer set specific for the viral nucleoprotein gene.
AB  - The filoviruses, Marburg virus (MARV) and Ebola virus (EBOV), are causative
      agents of severe hemorrhagic fever with high mortality rates in humans and non
      human primates. Sporadic outbreaks of filovirus infection have occurred in
      Central Africa and parts of Asia. Identification of the natural reservoir animals
      that are unknown yet and epidemiological investigations are current challenges to
      forestall outbreaks of filovirus diseases. The filovirus species identified
      currently include one in the MARV group and five in the EBOV group, with large
      genetic variations found among the species. Therefore, it has been difficult to
      develop a single sensitive assay to detect all filovirus species, which would
      advance laboratory diagnosis greatly in endemic areas. In this study, a highly
      sensitive universal RT-PCR assay targeting the nucleoprotein (NP) gene of
      filoviruses was developed. The genomic RNAs of all known MARV and EBOV species
      were detected by using an NP-specific primer set. In addition, this RT-PCR
      procedure was verified further for its application to detect viral RNAs in tissue
      samples of animals infected experimentally and blood specimens of infected
      patients. This assay will be a useful method for diagnostics and epidemiological
      studies of filovirus infections.

PMID- 21093486
TI  - Construction and properties of a recombinant pseudorabies virus with tetracycline
      regulated control of immediate-early gene expression.
AB  - A study was carried out to determine whether altering the control of expression
      of the IE180 gene of pseudorabies virus (PRV), by replacing the IE180 promoter
      with the tetracycline-responsive promoter (Ptet), affects virus replication and
      virulence. This PRV-BT90 mutant virus was constructed by complementation and
      recombination in Hela Tet-Off cells. The virus yield produced by infection of
      Hela Tet-Off cells with PRV-BT90 was similar to that of the parental virus
      vBecker2. Viral replication of PRV-BT90 was reduced in Vero cells as reflected by
      a reduction of virus yield and plating efficiency compared to vBecker2. PRV-BT90
      plaque formation in Hela Tet-Off cells was inhibited in the presence of
      doxycycline, whereas vBecker2 plaque formation was not affected. Subcutaneous
      infection of mice with the two viruses revealed a LD(50) higher than 10(6)
      TCID(50) for the PRV-BT90 mutant virus while the LD(50) was 178 TCID(50) for the
      vBecker2 parental virus.

PMID- 21093487
TI  - A reverse-transcription, loop-mediated isothermal amplification assay for
      detection of bovine ephemeral fever virus in the blood of infected cattle.
AB  - A novel reverse-transcription, loop-mediated isothermal amplification (RT-LAMP)
      assay for the detection of bovine ephemeral fever virus (BEFV) was developed and
      evaluated in this study. The RT-LAMP assay exhibited higher sensitivity when
      compared with conventional reverse-transcription polymerase chain reaction (RT
      PCR) and virus isolation methods. The specificity of the assay was determined by
      digestion of the RT-LAMP products with restriction enzyme and detection of BEFV
      serogroup rabies virus (RV). Using RT-LAMP, RT-PCR and virus isolation methods,
      36 blood samples were tested and the results indicated that RT-LAMP could detect
      early infection with BEFV. The RT-LAMP method is useful for the diagnosis of BEFV
      infection in blood samples.

PMID- 21093488
TI  - Viral entry inhibitors block dengue antibody-dependent enhancement in vitro.
AB  - Severe dengue virus (DENV) disease symptoms, including dengue hemorrhagic fever
      and dengue shock syndrome, have been correlated with the presence of pre-existing
      antibodies that enhance rather than neutralize infections in Fc receptor bearing
      cells. These antibodies can originate from previous infection with a different
      serotype of dengue, or from waning antibody titers that occur in infants and
      young children as they are weaned from breast milk that contains protective
      dengue-specific antibodies. Despite the apparent importance of this antibody
      dependent enhancement (ADE) effect, there has been no description of any specific
      inhibitors of this process. We explored DENV entry inhibitors as a potential
      strategy to block ADE. Two different peptide entry inhibitors were tested for the
      ability to block antibody-mediated DENV-2 infection of human, FcRII bearing K562
      cells in vitro. Both peptides were able to inhibit ADE, showing that entry
      inhibitors are possible candidates for the development of specific treatment for
      severe DENV infection.

PMID- 21093489
TI  - Single-dose intranasal administration with mDEF201 (adenovirus vectored mouse
      interferon-alpha) confers protection from mortality in a lethal SARS-CoV BALB/c
      mouse model.
AB  - Interferons (IFNs) are a first line of defense against viral infection. Herein we
      describe the use of an adenovirus vectored mouse IFN alpha gene (mDEF201) as a
      prophylactic and treatment countermeasure in a SARS-CoV-infected BALB/c mouse
      model. Complete survival protection was observed in mice given a single dose of
      mDEF201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal SARS-CoV
      challenge (p<0.001), and body weights of these treated mice were unaffected by
      the challenge. In addition, low doses of mDEF201 protected lungs in a dose
      dependent manner as measured by a reduction in gross pathology. Intranasal
      treatment with mDEF201 ranging from 10(6) to 10(8)PFU significantly protected
      mice against a lethal SARS-CoV infection in a dose dependent manner up to 12h
      post infection (p<0.001). The data suggest that mDEF201 is a new class of
      antiviral agent further development as treatment for SARS-CoV infections.

PMID- 21093490
TI  - Long-term inhibition of HIV-1 replication with RNA interference against cellular
      co-factors.
AB  - In this study we tested whether HIV-1 replication could be inhibited by stable
      RNAi-mediated knockdown of cellular co-factors. Cell lines capable of expressing
      shRNAs against 30 candidate co-factors implicated at different steps of the viral
      replication cycle were generated and analyzed for effects on cell viability and
      inhibition of HIV-1 replication. For half of these candidate co-factors we
      obtained knockdown cell lines that are less susceptible to virus replication. For
      three co-factors (ALIX, ATG16 and TRBP) the cell lines were resistant to HIV-1
      replication for up to 2 months. With these cells we could test the hypothesis
      that HIV-1 is not able to escape from RNAi-mediated suppression of cellular co
      factors, which was indeed not detected.

PMID- 21093491
TI  - The antidepressant action of imipramine and venlafaxine involves suppression of
      nitric oxide synthesis.
AB  - Depressive disorders represent a major public health problem worldwide. The
      limitations of current antidepressant drugs have warranted on-going research to
      identify pharmacological agents and strategies that offer a greater therapeutic
      efficacy. The NMDA/L-arginine nitric oxide (NO)-cyclic guanosine monophosphate
      (cGMP) cascade is an important signaling pathway that is also implicated in the
      regulation of depression. In animal models detecting antidepressant activity,
      distinct NO synthase inhibitors display antidepressant-like action. Therefore,
      the aim of current study was to evaluate whether pretreatment with L-arginine
      (precursor of NO) could counteract antidepressant-like effects of distinct
      antidepressant classes in the mouse forced swimming test (FST), and whether these
      drugs are able to modulate the nitric oxide synthesis in the brain. We found in
      the FST that pretreatment with L-arginine (500 mg/kg) counteracted the
      antidepressant-like effect of imipramine (IMI, 15 mg/kg) and venlafaxine (VENL, 6
      mg/kg), but not the effects of bupropion (BUPR, 20mg/kg) or fluoxetine (FLX,
      20mg/kg). Increasing the dose of L-Arg to 1000 mg/kg attenuated the
      antidepressant-like effects of BUPR, but did not modify the action of FLX. L
      Arginine was devoid of any locomotor effects on the animals. The effect of
      antidepressants on brain NO metabolism paralleled their behavioral action in case
      of IMI and VENL which decreased the nitrite+nitrate concentration in the brain.
      BUPR and FLX did not have any effect on brain nitrite+nitrate concentration.
      These results support the idea that some antidepressants are able to inhibit
      nitric oxide synthesis in the brain, an effect which could be mechanistically
      related to the ability of L-arginine to counteract their antidepressant-like
      effects.

PMID- 21093492
TI  - Multiple autism-like behaviors in a novel transgenic mouse model.
AB  - Autism spectrum disorder (ASD) diagnoses are behaviorally based with no defined
      universal biomarkers, occur at a 1:110 ratio in the population, and predominantly
      affect males compared to females at approximately a 4:1 ratio. One approach to
      investigate and identify causes of ASD is to use organisms that display abnormal
      behavioral responses that model ASD-related impairments. This study describes a
      novel transgenic mouse, MALTT, which was generated using a forward genetics
      approach. It was determined that the transgene integrated within a non-coding
      region on the X chromosome. The MALTT line exhibited a complete repertoire of ASD
      like behavioral deficits in all three domains required for an ASD diagnosis:
      reciprocal social interaction, communication, and repetitive or inflexible
      behaviors. Specifically, MALTT male mice showed deficits in social interaction
      and interest, abnormalities in pup and juvenile ultrasonic vocalization
      communications, and exhibited a repetitive stereotypy. Abnormalities were also
      observed in the domain of sensory function, a secondary phenotype prevalently
      associated with ASD. Mapping and expression studies suggested that the Fam46 gene
      family may be linked to the observed ASD-related behaviors. The MALTT line
      provides a unique genetic model for examining the underlying biological
      mechanisms involved in ASD-related behaviors.

PMID- 21093494
TI  - Blocking IL-1alpha but not IL-1beta increases susceptibility to chronic
      Mycobacterium tuberculosis infection in mice.
AB  - IL-1alpha and IL-1beta are potent inflammatory cytokines and important mediators
      of immune responses to intracellular pathogens such as Mycobacterium tuberculosis
      (Mtb). Here, we investigated the role of IL-1alpha and IL-1beta during chronic
      Mtb infection and spontaneous reactivation in mice. For long-term neutralization
      of IL-1alpha, IL-1beta or both, mice were immunized with virus-like particles
      (VLPs) displaying either of the cytokines, inducing strong and long-lasting
      neutralizing IgG responses. Blocking of IL-1alpha but not of IL-1beta resulted in
      increased susceptibility to chronic infection with Mtb. Neutralizing either IL
      1alpha or IL-1beta alone did not lead to increased reactivation of latent
      tuberculosis. The generation of antibodies neutralizing both IL-1alpha and IL
      1beta simultaneously, did not influence weight gain during Mtb reactivation and
      the slight increase in pulmonary bacillary counts were not significant when
      compared to control-immunized group. Thus, the results suggest that IL-1alpha is
      the major mediator of the IL-1RI-dependent and protective innate immune responses
      to Mtb in mice.

PMID- 21093493
TI  - Structural pathology underlying neuroendocrine dysfunction in schizophrenia.
AB  - Polydipsic hyponatremic schizophrenic (PHS) patients exhibit altered
      neuroendocrine activity that has been linked to their life-threatening water
      imbalance, as well as to impaired function and reduced volume of the anterior
      hippocampus. Polydipsic patients without hyponatremia (polydipsic normonatremic
      schizophrenics: PNS) exhibit similar, albeit less marked, changes in
      neuroendocrine activity and anterior hippocampal function, but not reduced
      anterior hippocampal volume. Indeed, reduced anterior hippocampal volume is seen
      in patients with normal water balance (nonpolydipsic normonatremic
      schizophrenics: NNS) whose neuroendocrine activity and anterior hippocampal
      function differ markedly from those with polydipsia. In an effort to reconcile
      these findings we measured hippocampal, amygdala and 3rd ventricle shapes in 26
      schizophrenic patients (10 PNS, 7 PHS, 9 NNS) and 12 healthy controls matched for
      age and gender. Bilateral inward deformations were localized to the anterior
      lateral hippocampal surface (part of a neurocircuit which modulates
      neuroendocrine responses to psychological stimuli) in PHS and to a lesser extent
      in PNS, while deformations in NNS were restricted to the medial surface.
      Proportional deformations of the right medial amygdala, a key segment of this
      neurocircuit, were seen in both polydipsic groups, and correlated with the volume
      of the 3rd ventricle, which lies adjacent to the neuroendocrine nuclei. Finally,
      these structural findings were most marked in those with impaired hippocampal
      mediated stress responses. These results reconcile previously conflicting data,
      and support the view that anterior lateral hippocampal pathology disrupts
      neuroendocrine function in polydipsic patients with and without hyponatremia. The
      relationship of these findings to the underlying mental illness remains to be
      established.

PMID- 21093495
TI  - Infection of mouse bone marrow-derived dendritic cells by live attenuated
      Japanese encephalitis virus induces cells maturation and triggers T cells
      activation.
AB  - An attenuated Japanese encephalitis virus (JEV) strain SA14-14-2, generated from
      the wild strain SA14, is an effective live vaccine against JEV infection. It has
      led to a significant decrease in JEV infection around the world. Although it is
      highly effective, the mechanism for its robust immunity was not well
      investigated. In this study, the interaction of SA14-14-2 with bone marrow
      derived dendritic cells (bmDCs) was investigated. Our results showed that the
      infection of bmDCs with SA14-14-2 resulted in viral replication and upregulation
      of bmDC maturation marker molecules (CD40, CD80, CD83 and MHC I). SA14-14-2
      infection also stimulated the production of interferon-alpha (IFN-alpha),
      monocyte chemoattractant protein-1 (MCP-1/CCL2), tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) of bmDC. Both MLR and ELISPOT assay showed an
      enhanced allostimulatory capacity of SA14-14-2-infected bmDCs. Furthermore, the
      SA14-14-2-infected bmDCs impaired the expansion of Foxp3+ regulatory T (Treg)
      cells with immunosuppressive potential, suggesting that SA14-14-2 infection
      induced antiviral immunity rather than immunosuppression. Taken together, our
      results indicated that SA14-14-2 infection caused bmDC maturation, changed the
      expression profiles of several cytokines, and triggered T cell activation. This
      offered an insight in the immunologic mechanisms associated with the high
      efficiency of the SA14-14-2 vaccine.

PMID- 21093496
TI  - Diphtheria-tetanus-pertussis vaccine administered simultaneously with measles
      vaccine is associated with increased morbidity and poor growth in girls. A
      randomised trial from Guinea-Bissau.
AB  - BACKGROUND: Combined vaccination with diphtheria-tetanus-pertussis (DTP) and
      measles vaccine (MV) has been associated with increased mortality in
      observational studies. Among children missing MV and a dose of DTP and oral polio
      vaccine (OPV), we conducted a randomised trial of providing MV+DTP+OPV
      simultaneously, as currently recommended, or MV+OPV only, and examined the effect
      on morbidity and growth. We hypothesised that the MV+OPV group would experience
      less morbidity and grow better. Due to previous observations of sex differences
      in the non-specific effects of vaccinations, we analysed all data stratified by
      sex. METHODS: At the Bandim Health Project in Guinea-Bissau, 568 children who
      were due to receive MV and who were missing either DTP3 or DTP booster were
      enrolled in the study. A subgroup of 332 children was followed intensively to
      register adverse events and infections in the first month after vaccination. A
      subgroup of 276 children was followed every third month for a year to monitor
      growth. All children were followed for one year for infectious diseases,
      consultations, and hospitalisations. RESULTS: As expected, adverse events were
      more common in the MV+DTP+OPV group; diarrhoea and use of medication were
      increased among girls but not among boys (both p=0.02, test of interaction
      between DTP and sex). Febrile disease with vesicular rash, as well as
      consultations and hospitalisations tended to be more common in the MV+DTP+OPV
      group than in the MV+OPV group; the hazard ratio (HR) for febrile disease with
      vesicular rash was 1.86 (1.00; 3.47). The strongest tendencies for more febrile
      diseases and hospitalisations in the MV+DTP+OPV group were found in girls.
      Overall, growth did not differ by randomisation group. However, results differed
      by sex. Girls in the MV+DTP+OPV group had a consistent pattern of worse z-scores
      for weight, height, and mid-upper-arm-circumference (MUAC) than girls in the
      MV+OPV group. The effect was opposite for boys, with boys in the MV+OPV group
      faring worse than those in the MV+DTP+OPV group, the interaction test for sex and
      DTP being significant for weight at 6 and 9 months, for MUAC at 12 months and for
      weight-for-height at 3 and 9 months after randomisation. CONCLUSION: This is the
      first randomised trial of the non-specific effects of DTP and supports that these
      effects may be sex-differential and of clinical and anthropometric importance.
      Combined vaccination with DTP+MV+OPV may be detrimental for girls.

PMID- 21093497
TI  - Analysis of porcine circovirus type 1 detected in Rotarix vaccine.
AB  - A metagenomic analysis of live human vaccines has recently demonstrated the
      presence of porcine circovirus type 1 (PCV1) DNA in the paediatric vaccine
      Rotarix used in the prevention of acute gastroenteritis. Using real-time PCR for
      PCV1, titres of PCV1 DNA in several batches of Rotarix were found to be in the
      order of 6-7 log(10) copies per dose. Pre-treatment of the reconstituted vaccine
      with the nuclease Benzonase, followed by extraction of nucleic acid and
      quantification of PCV1 DNA by real-time PCR, revealed that there was no loss of
      PCV1 DNA titre compared to untreated controls, suggesting that the porcine viral
      DNA was present in the vaccine in an encapsidated form. PCV1 permissive PS cells,
      human HEK293 and Vero cells, used for vaccine production, were infected with
      Rotarix or PCV1, respectively, and subjected to immune fluorescence and RT-PCR.
      Viral genomes were present in Rotarix-incubated as well as PCV1-infected cells,
      while viral transcription was seen only in PCV1-infected cells. Similarly, PCV1
      specific protein expression was observed in PCV1-infected cells, but not in cells
      treated with Rotarix. Passaging of the supernatant indicated productive infection
      in PCV1-infected PS cells, but not in HEK293 and Vero cells or in any cell line
      incubated with Rotarix. PCV1 DNA present in Rotarix was protected from Benzonase
      digestion; however, PCV1 was not recognized in immune electron microscopy and
      unable to infect PS, HEK293 or Vero cells, suggesting that the high amount of
      PCV1 DNA present in Rotarix does not reflect a corresponding proportion of
      biologically active virus particles.

PMID- 21093498
TI  - Adjuvating the adjuvant: facilitated delivery of an immunomodulatory
      oligonucleotide to TLR9 by a cationic antimicrobial peptide in dendritic cells.
AB  - IC31((r)) is a novel bi-component vaccine adjuvant consisting of the peptide
      KLKL(5)KLK (KLK) and the TLR9 agonist oligonucleotide d(IC)(13) (ODN1a). While
      membrane-interacting properties of KLK and immuno-modulating capabilities of
      ODN1a have been characterized in detail, little is known of how these two
      molecules function together and synergize in interacting with their primary
      target cells, dendritic cells (DCs). We have found that KLK-triggered aggregates
      entrapped ODN1a and these complexes readily associated with the DC cell surface.
      KLK stimulated the uptake and internalization of ODN1a via endocytosis, while the
      bulk of the peptide remained associated with the cell periphery. ODN1a co
      localized with early and late endosomes as well as endoplasmic reticular
      structures. ODN1a co-localized with TLR9 positive compartments following KLK
      mediated uptake. These features did not depend on the expression of TLR-9. Our
      results reveal novel mechanisms that allow KLK to enhance the effects of the TLR
      9 ligand ODN1a in immunomodulation.

PMID- 21093500
TI  - Developmental expression of high molecular weight tropomyosin isoforms in
      Mesocestoides corti.
AB  - Tropomyosins are a family of actin-binding proteins with diverse roles in actin
      filament function. One of the best characterized roles is the regulation of
      muscle contraction. Tropomyosin isoforms can be generated from different genes,
      and from alternative promoters and alternative splicing from the same gene. In
      this work, we have isolated sequences for tropomyosin isoforms from the cestode
      Mesocestoides corti, and searched for tropomyosin genes and isoforms in other
      flatworms. Two genes are conserved in the cestodes M. corti and Echinococcus
      multilocularis, and in the trematode Schistosoma mansoni. Both genes have the
      same structure, and each gene gives rise to at least two different isoforms, a
      high molecular weight (HMW) and a low molecular weight (LMW) one. Because most
      exons are duplicated and spliced in a mutually exclusive fashion, isoforms from
      one gene only share one exon and are highly divergent. The gene duplication
      preceded the divergence of neodermatans and the planarian Schmidtea mediterranea.
      Further duplications occurred in Schmidtea, coupled to the selective loss of
      duplicated exons, resulting in genes that only code for HMW or LMW isoforms. A
      polyclonal antibody raised against a HMW tropomyosin from Echinococcus granulosus
      was demonstrated to specifically recognize HMW tropomyosin isoforms of M. corti,
      and used to study their expression during segmentation. HMW tropomyosins are
      expressed in muscle layers, with very low or absent levels in other tissues. No
      expression of HMW tropomyosins is present in early or late genital primordia, and
      expression only begins once muscle fibers develop in the genital ducts.
      Therefore, HMW tropomyosins are markers for the development of muscles during the
      final differentiation of genital primordia.

PMID- 21093499
TI  - Genome-wide RNAi screens in African trypanosomes identify the nifurtimox
      activator NTR and the eflornithine transporter AAT6.
AB  - To be effective, therapeutic compounds must typically enter target cells and, in
      some cases, must be concentrated or modified. Thus, uptake and activation
      mechanisms often form the basis of selectivity against infectious agents. Loss-of
      function screens can be used to identify proteins involved in drug uptake and
      metabolism and may also identify clinically relevant potential resistance
      mechanisms. We used a genome-scale RNA interference (RNAi) library to identify
      loss-of-function resistance mechanisms in bloodstream-form Trypanosoma brucei.
      Nifurtimox-Eflornithine Combination Therapy (NECT) was recently introduced for
      Human African Trypanosomiasis and we focus on these drugs here. Screens for
      resistance to nifurtimox and a related drug, benznidazole, identified loss of
      nitroreductase (NTR) pro-drug activator function. A screen for resistance to the
      amino-acid analogue, eflornithine, identified loss of amino-acid transporter
      (AAT6) function. Our results confirm recent findings and suggest that NTR or AAT6
      loss-of-function represent major potential mechanisms of resistance to these
      drugs. Thus, bloodstream-form T. brucei RNAi libraries present a versatile tool
      for selective genetic screening and for the rapid identification of drug
      activation, uptake and potential resistance mechanisms.

PMID- 21093501
TI  - Optimisation of an in vitro antifungal protein assay for the screening of
      potential antifungal proteins against Leptosphaeria maculans.
AB  - Canola is second only to soybean as the most important oilseed crop in the world.
      The global production of canola is forecast to continue to increase and as a
      result the canola industry will continue to flourish. However, it is threatened
      by several fungal diseases that affect canola and cost producers hundreds of
      millions of dollars a year in reduced yield and quality. Blackleg is the most
      common and devastating disease of canola and is caused by the fungus
      Leptosphaeria maculans. The fungus can infect any part of the plant at all growth
      stages and is a serious threat to the canola industry. Novel and more efficient
      antifungal agents which interfere with fungal growth and development are clearly
      needed to control this pathogen. This paper reports the establishment of a simple
      functional assay system for the screening of antifungal proteins against a
      virulent strain of L. maculans.

PMID- 21093502
TI  - Modulation of neurotransmitter receptors and synaptic differentiation by proteins
      containing complement-related domains.
AB  - Neurotransmitter receptors play central roles in basic neurotransmission and
      synaptic plasticity. Recent studies have revealed that some transmembrane and
      extracellular proteins bind to neurotransmitter receptors, forming protein
      complexes that are required for proper synaptic localization or gating of core
      receptor molecules. Consequently, the components of these complexes contribute to
      long-term potentiation, a process that is critical for learning and memory. Here,
      we review factors that regulate neurotransmitter receptors, with a focus on
      proteins containing CUB (complement C1r/C1s, Uegf, Bmp1) or CCP (complement
      control protein) domains, which are frequently found in complement system
      proteins. Proteins that contain these domains are structurally distinct from
      TARPs (transmembrane AMPA receptor regulatory proteins), and may constitute new
      protein families that modulate either the localization or function of
      neurotransmitter receptors. In addition, other CCP domain-containing proteins
      participate in dendritic patterning and/or synaptic differentiation, although
      current evidence has not identified any direct activities on neurotransmitter
      receptors. Some of these proteins are involved in pathologic conditions such as
      epileptic seizure and mental retardation. Together, these lines of information
      have shown that CUB and CCP domain-containing proteins contribute to a wide
      variety of neuronal events that ultimately establish neural circuits.

PMID- 21093503
TI  - Functional evaluation of paraplegic monkeys (Macaca mulatta) over fourteen months
      post-lesion.
AB  - We report on the neurological and neurophysiological findings obtained from two
      adult Macaca mulatta sustaining complete spinal cord transections at T8-T9. We
      performed periodic neurological exams, recorded motor evoked potentials (MEPs)
      following transcranial magnetic stimulation (TMS), and recorded electromyograms
      (EMGs) during the execution of a lower limb motor test. The main observations
      were: (1) the spinal shock period lasted less than a week; tendon, cutaneous and
      withdrawal reflexes were uneven in range and occurrence, and Babinski's sign was
      not observed; (2) a protracted functional lesion in the tibial and common
      peroneal nerves appeared bilaterally early in the post-lesional period; (3) MEPs
      were elicited by TMS in the quadriceps muscle of both monkeys; they were recorded
      as early as the 5th week after lesion in one of the monkeys, and they persisted
      throughout the post-lesional period in both monkeys; and (4) motor unit action
      potentials in the quadriceps muscle recorded by EMG were simultaneous with
      attempts to perform intentional lower limb movements from post-lesion month 11 to
      13.5 in both monkeys. The last two sets of observations argue in favor of a
      partial cortico-spinal functional gain and suggest that spinal cord regeneration
      can occur after complete spinal cord injury in primates.

PMID- 21093504
TI  - Role of group A p21-activated kinases in the anti-apoptotic activity of the
      pseudorabies virus US3 protein kinase.
AB  - The alphaherpesvirus US3 kinase is a conserved multifunctional serine/threonine
      kinase that plays a role in several processes, including modulation of the actin
      cytoskeleton, egress of virus particles from the nucleus and inhibition of
      apoptosis. However, the mechanisms used by the US3 protein to exert its functions
      remain poorly understood. Recently, we identified the group A p21-activated
      kinases PAK1 and PAK2 as important effectors in the US3-mediated cytoskeletal
      rearrangements. Here, we investigated if group A PAKs are also involved in the
      anti-apoptotic properties of US3. Infection experiments using a group A PAK
      inhibitor pointed at a moderate role for group A PAKs in the anti-apoptotic
      properties of US3. Furthermore, infection assays using wild type and US3null PRV
      in wild type MEF, PAK1(-/-) MEF and PAK2(-/-) MEF indicated that PAK2 does not
      play a role in US3-mediated inhibition of apoptosis during infection, whereas
      PAK1 plays a significant, yet limited role. Experiments in US3-transfected MEF
      using staurosporine as apoptosis trigger confirmed these observations. These
      results show that PAK1 plays a significant, yet limited, role in the anti
      apoptotic activity of US3.

PMID- 21093505
TI  - Ammonium carbamates as highly active transdermal permeation enhancers with a dual
      mechanism of action.
AB  - Transdermal permeation enhancers are compounds that temporarily increase drug
      flux through the skin by interacting with constituents of the stratum corneum.
      Transkarbam 12 (T12) is a highly active, broad-spectrum, biodegradable enhancer
      with low toxicity and low dermal irritation. We show here that T12 acts by a dual
      mechanism of action. The first part of this activity is associated with its
      ammonium carbamate polar head as shown by its pH-dependent effects on the
      permeation of two model drugs. Once this ammonium carbamate penetrates into the
      stratum corneum intercellular lipids, it rapidly decomposes releasing two
      molecules of protonated dodecyl 6-aminohexanoate (DDEAC) and carbon dioxide. This
      was observed by thermogravimetric analysis and infrared spectroscopy. This step
      of T12 action influences drug permeation through lipidic pathways, not through
      the aqueous pores (polar pathway) as shown by its effects on various model drugs
      and electrical impedance. Consequently, protonated DDEAC released in the stratum
      corneum is also an active enhancer. It broadens the scope of T12 action since it
      is also able to increase permeation of hydrophilic drugs that prefer the pore
      pathway. Thus, this dual effect of T12 is likely responsible for its favorable
      properties, which make it a good candidate for prospective clinical use.

PMID- 21093506
TI  - Motivation for choice and healthiness perception of calorie-reduced dairy
      products. a cross-cultural study.
AB  - Understanding consumers' motives for selecting calorie-reduced dairy products are
      important to provide targeted communication to different consumer segments. The
      aim of this study was to identify motives for consumption of calorie-reduced
      dairy products among young consumers, and to identify how these consumers
      perceive the healthiness of such products compared to other food products.
      Consumers, aged 18-30 years, from Norway (n=118), Denmark (n=125), and California
      (n=127) participated in this cross-cultural study. The respondents sorted 24
      statements referring to motives for choosing calorie-reduced yoghurt and cheese.
      The study also assessed the aspect of perceived healthiness of these products in
      comparison with a selection of other food products using a two-step ranking
      procedure. The data were analysed using chi-square analysis, Friedman's test and
      Principal Component Analysis (PCA). The results show that fat content,
      healthiness and taste were the most important motivators for choice of the
      calorie-reduced dairy products. In all three countries salmon was perceived as
      the healthiest among the products presented. The calorie-reduced dairy products
      were ranked as relatively healthy, with yoghurt ranked as healthier than cheese.
      Although cross-cultural differences existed in motives for choice and perceived
      healthiness of the products, the similarities between the countries were evident
      in this study.

PMID- 21093507
TI  - Cholecystokinin-8 activates myenteric neurons in 21- and 35-day old but not 4-
      and 14-day old rats.
AB  - Cholecystokinin (CCK) activates the myenteric neurons of adult rats. The goal of
      this work is to determine the ontogeny of this activation by CCK-8 in the
      myenteric plexus of the duodenum (2cm immediately following the pyloric sphincter
      aborally) and compare it with that of the dorsal vagal complex (DVC) - which
      occurs in 1-day old pups. Despite the existence of both of the CCK receptors,
      CCK(1) and CCK(2), in 4, 14, 21 and 35 day old rats, CCK-8 (0, 5, 10, 20 and
      40MUg/kg, i.p.) increased Fos-like immunoreactivity (Fos-LI, a marker for
      neuronal activation) in the myenteric neurons of 21- and 35-day old rats but in
      the DVC of all age groups. As such, this belated activation of myenteric neurons
      by CCK-8 compared to the DVC may reflect a delayed role for these neurons in CCK
      related functions.

PMID- 21093508
TI  - The control of Malpighian tubule secretion in a predacious hemipteran insect, the
      spined soldier bug Podisus maculiventris (Heteroptera, Pentatomidae).
AB  - Spined soldier bugs, Podisus maculiventris, are heteropteran insects that feed
      voraciously on other insects, particular the soft bodied larval forms of
      Lepidoptera and Coleoptera. The response of P. maculiventris Malpighian tubules
      (MTs) to serotonin and known diuretic and antidiuretic peptides has been
      investigated, and is compared with that of MT from the hematophagous and
      phytophagous heteropteran bugs Rhodnius prolixus and Acrosternum hilare,
      respectively. A CRF-related peptide diuretic hormone (DH) from the termite
      Zootermopsis nevadensis (Zoone-DH) stimulated MT secretion, which was reversed by
      a member of the CAP(2b) family of peptides from A. hilare (Acrhi-CAP(2b)-2), an
      antidiuretic effect. Serotonin had no effect on secretion, neither did a
      representative calcitonin-like DH, kinin, tachykinin-related peptide, and an
      antidiuretic factor from the mealworm Tenebrio molitor (Tenmo-ADFb) in both P.
      maculiventris or A. hilare. Serotonin is a DH in R. prolixus, and its lack of
      effect on MT from P. maculiventris and A. hilare suggests this is an adaptation
      to hematophagy. On the other hand, the antidiuretic activity of members of the
      CAP(2b) family in all three bugs is consistent with this being a heteropteran
      feature rather than a specialism for hematophagy.

PMID- 21093509
TI  - The antimicrobial peptide, tilapia hepcidin 2-3, and PMA differentially regulate
      the protein kinase C isoforms, TNF-alpha and COX-2, in mouse RAW264.7
      macrophages.
AB  - The antimicrobial and immunomodulatory functions of the antimicrobial peptide,
      tilapia hepcidin (TH)2-3, were previously studied. Herein, we report the
      differential modulation of protein kinase C (PKC)-associated proteins by TH2-3,
      and the PKC activator, phorbol 12-myristate 13-acetate (PMA), in RAW264.7
      macrophages. Treatment with TH2-3 at 40 or 80MUg/ml did not affect the cell
      morphology, but TH2-3 at 120MUg/ml produced morphological changes similar to
      those after treatment with PMA in RAW264.7 cells. The coexistence of the PKC
      inhibitor, Ro-31-8220, prevented morphological changes induced by either PMA or
      120MUg/ml TH2-3 in RAW264.7 cells. Since PMA is known to induce expression of the
      proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, activation of the
      TNF-alpha promoter in response to TH2-3 and PMA treatments in lipopolysaccharide
      (LPS)-stimulated cells was compared. In LPS-stimulated RAW264.7 cells, TNF-alpha
      promoter activity was significantly suppressed by TH2-3, but not by PMA. In
      addition, PMA activated prostaglandin synthase-associated cyclooxygenase (COX)-2
      proteins on the cell surface, while the presence of TH2-3 inhibited its
      expression. Western blotting demonstrated that the expressions of PKC-MU,
      phosphorylated (p)-PKCMU at serine (S)-744, and p-PKCdelta were activated by PMA,
      but were suppressed by TH2-3. In addition, p-PKC at S-916 was activated by TH2-3
      and inhibited by PMA. In conclusion, the differential regulation of PKC isoforms
      by PMA and TH2-3 may influence morphological changes and regulation of TNF-alpha
      in RAW264.7 cells.

PMID- 21093510
TI  - In vitro leptin treatment of rainbow trout hypothalamus and hindbrain affects
      glucosensing and gene expression of neuropeptides involved in food intake
      regulation.
AB  - The aim of the present study was to evaluate in hypothalamus and hindbrain of
      rainbow trout in vitro the effect of leptin treatment on glucosensing capacity
      and the expression of orexigenic and anorexigenic peptides involved in the
      control of food intake. In a first experiment, the response of parameters
      involved in glucosensing (GK, PK and GSase activities; GK expression and glucose;
      glycogen and DHAP levels) and the expression of orexigenic (NPY) and anorexigenic
      (POMC, CART, CRF) peptides was assessed in hypothalami and hindbrain incubated
      for 1h with 2, 4 or 8mM d-glucose alone (controls) or with 10nM leptin, or with
      10nM leptin plus inhibitors of leptin signaling pathways (50nM wortmannin and
      500nM AG490). Leptin treatment increased levels in parameters involved in
      glucosensing. Leptin treatment decreased NPY mRNA levels in hypothalamus without
      affecting the expression of the other peptides assessed. Leptin effects were
      reverted in the presence of inhibitors for all parameters assessed suggesting the
      involvement of JAK/STAT and IRS-PI(3)K pathways. In a second experiment, we
      observed time-dependent (1-3h) and dose (10, 20 and 50nM)- effects of leptin
      treatment in decreasing NPY mRNA levels without affecting expression of the other
      peptides assessed. Considering the orexigenic action of NPY in fish, it seems
      that the anorexic effect of leptin can be mediated by reduced expression of NPY
      occurring in hypothalamus, and that change can be related to the activation of
      the glucosensing system occurring simultaneously.

PMID- 21093511
TI  - RNA interference of insulin-related peptide and neuroparsins affects
      vitellogenesis in the desert locust Schistocerca gregaria.
AB  - The 'classic' insect hormones, juvenile hormone and 20-hydroxyecdysone, can
      stimulate vitellogenesis and/or ovarian development in adult females of several
      insect species. Accumulating evidence also indicates a crucial role in female
      reproductive physiology for peptide hormones, such as insulin-related peptides
      (IRPs) and neuroparsins (NPs). Especially in dipteran species, IRP signaling has
      been shown to regulate female reproductive events. The first NP was originally
      identified from the migratory locust (Locusta migratoria) as an antigonadotropic
      factor that delayed vitellogenesis. Moreover, NP family members display sequence
      similarities with the N-terminal domain of vertebrate insulin-like growth factor
      binding proteins (IGFBPs). In the current study, RNA interference (RNAi) was
      employed to investigate the possible involvement of IRP and NPs in the control of
      the female desert locust (Schistocerca gregaria) reproductive system. The cDNAs
      encoding an IRP (Scg-IRP) and four NPs (Scg-NPs) had previously been cloned from
      S. gregaria. An RNAi-mediated knock-down of either Scg-NP or Scg-IRP transcript
      levels was induced in adult female desert locusts and the subsequent effects were
      analyzed. Knock-down of the Scg-NPs or Scg-IRP affected vitellogenin transcript
      levels and oocyte growth in a positive and negative way, respectively. The
      current findings are indicative for a role of Scg-NPs and Scg-IRP in the control
      of vitellogenin synthesis. A plausible hypothesis is that Scg-IRP may act as a
      sensor of the nutritional and metabolic status that determines whether
      vitellogenesis can occur. That the same processes were affected in opposite ways
      in both RNAi experiments offers an extra argument for antagonizing roles of Scg
      NPs and Scg-IRP.

PMID- 21093512
TI  - Applications of antimicrobial peptides from fish and perspectives for the future.
AB  - Fish are a major component of the aquatic fauna. Like other organisms, fish
      secrete different kinds of antimicrobial peptides (AMPs), which are positively
      charged short amino-acid-chain molecules involved in host defense mechanisms.
      Environmental hazards and the greenhouse effect have led to increased evolution
      of drug- and vaccine-resistant pathogenic strains, and it is necessary to find
      new drugs with structural uniqueness to fight them. Aquatic sources contain
      thousands of fish species, and each secretes AMPs with structural differences
      which can be used by the pharmaceutical industry in its search for novel drugs to
      treat drug-resistant pathogens. Not only limited to antimicrobial functions, AMPs
      possess other desirable characteristics which may be exploited in the near
      future. In this review, we list fish AMPs available from published reports, and
      discuss application-oriented functions of these AMPs. Notably, the possibilities
      of using fish AMPs as antimicrobial agents, vaccine adjuvants, inactivated
      vaccines, and antitumor agents are discussed in this review.

PMID- 21093513
TI  - Toward a consensus nomenclature for insect neuropeptides and peptide hormones.
AB  - The nomenclature currently in use for insect neuropeptide and peptide hormone
      families is reviewed and suggestions are made as to how it can be rationalized.
      Based upon this review, a number of conventions are advanced as a guide to a more
      rationale nomenclature. The scheme that is put forward builds upon the binomial
      nomenclature scheme proposed by Raina and Gade in 1988, when just over 20 insect
      neuropeptides had been identified. Known neuropeptides and peptide hormones are
      assigned to 32 structurally distinct families, frequently with overlapping
      functions. The names given to these families are those that are currently in use,
      and describe a biological function, homology to known invertebrate/vertebrate
      peptides, or a conserved structural motif. Interspecific isoforms are identified
      using a five-letter code to indicate genus and species names, and intraspecific
      isoforms are identified by Roman or Arabic numerals, with the latter used to
      signify the order in which sequences are encoded on a prepropeptide. The proposed
      scheme is sufficiently flexible to allow the incorporation of novel peptides, and
      could be extended to other arthropods and non-arthropod invertebrates.

PMID- 21093514
TI  - Tilapia (Oreochromis mossambicus) antimicrobial peptide, hepcidin 1-5, shows
      antitumor activity in cancer cells.
AB  - The inhibitory function of tilapia hepcidin (TH)1-5, an antimicrobial peptide,
      was not examined in previous studies. In this study, we synthesized the TH1-5
      peptide and tested TH1-5's antitumor activity against several tumor cell lines.
      We show that TH1-5 inhibited the proliferation of tumor cells and reduced colony
      formation in a soft agar assay. Scanning electron microscopy and transmission
      electron microscopy showed that TH1-5 altered the membrane structure similar to
      the function of a lytic peptide. Acridine orange/ethidium bromide staining, a
      wound-healing assay, and a flow cytometric analysis showed that TH1-5 induced
      necrosis with high-concentration treatment and induced apoptosis with low
      concentration treatment. Inflammation is known to be closely associated with the
      development of cancer. TH1-5 showing anti-inflammatory effects in a previous
      publication induced us to evaluate the anti-inflammatory effects in cancer cell
      lines through the expressions of immune-related genes after being treated with
      the TH1-5 peptide. However, real-time qualitative RT-PCR indicated that TH1-5
      treatment induced downregulation of the expressions of interleukin (IL)-6, IL-8,
      IL-12, IL-15, interferon-gamma, CTSG, caspase-7, and Bcl-2, and upregulation of
      IL-2 and CAPN5 in HeLa cells, and upregulation of IL-8 and CTSG in HT1080 cells.
      These results suggest that TH1-5 possibly induces an inflammatory response in
      HeLa cells, but not in HT1080 cells. Overall, these results indicate that TH1-5
      possesses the potential to be a novel peptide for cancer therapy.

PMID- 21093515
TI  - Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via
      NRF2-ARE signaling in microglial BV2 cells.
AB  - Xanthohumol (2',4',4-trihydroxy-6'-methoxy-3'-prenylchalcone) is a major chalcone
      derivative isolated from hop (Humulus lupulus L.) commonly used in brewing due to
      its bitter flavors. Xanthohumol has anti-carcinogenic, free radical-scavenging,
      and anti-inflammatory activities, but its precise mechanisms are not clarified
      yet. The basic leucine zipper (bZIP) protein NRF2 is a key transcription factor
      mediating the antioxidant and anti-inflammatory responses in animals. Therefore,
      we tested whether xanthohumol exerts anti-inflammatory activity in mouse
      microglial BV2 cells via NRF2 signaling. Xanthohumol significantly inhibited the
      excessive production of inflammatory mediators NO, IL-1beta, and TNF-alpha, and
      the activation of NF-kappaB signaling in LPS-induced stimulated BV2 cells.
      Xanthohumol up-regulated the transcription of NAD(P)H:quinone oxidoreductase 1
      (NQO1) and heme oxygenase-1 (HO-1), and increased the level of the endogenous
      antioxidant GSH. In addition, xanthohumol induced nuclear translocation of NRF2
      and further activation of ARE promoter-related transcription. The anti
      inflammatory response of xanthohumol was attenuated by transfection with NRF2
      siRNA and in the presence of the HO-1 inhibitor, ZnPP, but not the NQO1
      inhibitor, dicoumarol. Taken together, our study suggests that xanthohumol exerts
      anti-inflammatory activity through NRF2-ARE signaling and up-regulation of
      downstream HO-1, and could be an attractive candidate for the regulation of
      inflammatory responses in the brain.

PMID- 21093516
TI  - 17beta-estradiol attenuates programmed cell death in cortical pericontusional
      zone following traumatic brain injury via upregulation of ERalpha and inhibition
      of caspase-3 activation.
AB  - Pericontusional zone (PCZ) of traumatic cerebral contusion is a target of
      pharmacological intervention. It is well studied that 17beta-estradiol has a
      protective role in ischemic brain injury, but its role in brain protection of
      traumatic brain damage deserves further investigation, especially in
      pericontusional zone. Here we show that 17beta-estradiol enhances the protein
      expression and mRNA induction of estrogen alpha receptor (ERalpha) and prevents
      from programmed cell death in cortical pericontusional zone. ERalpha specific
      antagonist blocks this protective effect of 17beta-estradiol. Caspase-3
      activation occurs in cortical pericontusional zone of the oil-treated injured rat
      brain and its activation is inhibited by 17beta-estradiol treatment.
      Additionally, ERalpha specific antagonist reverses this inhibition. Pan-caspase
      inhibitor also protect cortical pericontusional zone from programmed cell death.
      Our present study indicates 17beta-estradiol protects from programmed cell death
      in cortical pericontusional zone via enhancement of ERalpha and decrease of
      caspase-3 activation.

PMID- 21093517
TI  - Neuroprotective effects of SCM198 on 6-hydroxydopamine-induced behavioral deficit
      in rats and cytotoxicity in neuronal SH-SY5Y cells.
AB  - 6-Hydroxydopamine (6-OHDA), one of the most investigated Parkinson's disease
      neurotoxins, is widely used to study mechanisms of cell death in dopaminergic
      neurons. In the present study, we demonstrated that SCM198, a new compound based
      on the active component of Herba leonuri, significantly reduced 6-OHDA-induced
      cell death in dopaminergic SH-SY5Y cells and attenuated apomorphine-elicited
      rotational behavior in 6-OHDA-lesioned rats. Pretreatment with SCM198 (0.001,
      0.01, 0.1, 1, and 10 MUM) concentration-dependently increased the cell viability
      as measured in MTT and LDH leakage assays compared with 6-OHDA-injured cells.
      Tocopherol, an antioxidant used as positive control, had similar effect at 10 MUM
      to SCM198 1 MUM. Furthermore, we assessed oxidative stress and subsequent
      apoptosis, the critical players in dopaminergic neurodegeneration, with 0.1, 1,
      and 10 MUM of SCM198 in SH-SY5Y cells exposed to 6-OHDA. Pretreatment with SCM198
      significantly increased antioxidant enzyme superoxide dismutase activity,
      ameliorated intracellular reactive oxygen species generation, prevented the
      dissipation of mitochondrial membrane potential, decreased apoptotic cell death
      in Hoechst 33258 staining, as well as down-regulated Bax and up-regulated Bcl-2
      in both mRNA and protein levels compared with 6-OHDA damaged cells. Moreover,
      intragastrical administration of SCM198 (18 or 60 mg kg-1 day-1) for 4 weeks
      significantly ameliorates apomorphine-induced contralateral rotations in 6-OHDA
      lesioned rats. These results support the neuroprotective effects of SCM198
      against 6-OHDA-induced toxicity in vivo and in vitro with the underlying
      mechanisms of inhibiting oxidative stress and apoptosis. Therefore we suggest
      that SCM198 might provide a useful therapeutic strategy for neurodegenerative
      diseases such as Parkinson's disease.

PMID- 21093518
TI  - Major histocompatibility complex class III (C2, C4, factor B) and C3 gene
      variants in patients with pulmonary tuberculosis.
AB  - The complement system is an integral part of the host immune system and plays an
      immunoregulatory role at the interface of innate and acquired immune responses.
      Limited data are available on the influence of variations in complement genes in
      infectious diseases such as pulmonary tuberculosis (PTB). The aim of this study
      was to investigate the role of genetic variations in complement system components
      C2, C4, BF, and C3 in PTB (n = 125) compared with healthy controls (n = 125) in
      the Indian population. The study showed, for the first time, an increased
      occurrence of null alleles at the C4A, i.e., C4AQ0; an increased frequency of
      BF*FA and C3*F in patients with PTB compared with healthy individuals, and
      contributed a risk with odds ratios of 18.16 (95% confidence interval [CI] = 3.0
      108.6, p = 0.0004), 2.9 (95% CI = 1.9-4.37, p(c) = 3.15E-06), and 2.26 (95% CI =
      1.5-3.3, p(c) = 6.7E-05), respectively. A combinatorial analysis of complement
      gene variants as risk determinants and their phenotypic effects in various
      populations may provide unique insights into the genetic basis of susceptibility
      to PTB.

PMID- 21093519
TI  - Vulnerability to chronic subordination stress-induced depression-like disorders
      in adult 129SvEv male mice.
AB  - Exposure to stressful life events is intimately linked with vulnerability to
      neuropsychiatric disorders such as major depression. Pre-clinical animal models
      offer an effective tool to disentangle the underlying molecular mechanisms. In
      particular, the 129SvEv strain is often used to develop transgenic mouse models
      but poorly characterized as far as behavior and neuroendocrine functions are
      concerned. Here we present a comprehensive characterization of 129SvEv male
      mice's vulnerability to social stress-induced depression-like disorders and
      physiological comorbidities. We employed a well characterized mouse model of
      chronic social stress based on social defeat and subordination. Subordinate
      129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads
      weight and basal plasma corticosterone. Home cage phenotyping revealed a
      suppression of spontaneous locomotor activity and transient hyperthermia.
      Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response
      toward a novel but palatable food, increased anxiety in the elevated plus maze
      and social avoidance of an unfamiliar male mouse. A direct measured effect of the
      stressfulness of the living environment, i.e. the amount of daily aggression
      received, predicted the degree of corticosterone level and locomotor activity but
      not of the other parameters. This is the first study validating a chronic
      subordination stress paradigm in 129SvEv male mice. Results demonstrated
      remarkable stress vulnerability and establish the validity to use this mouse
      strain as a model for depression-like disorders.

PMID- 21093521
TI  - Effects of repetitive transcranial magnetic stimulation on late-onset
      hallucinations: a case report.

PMID- 21093520
TI  - The WAG/Rij strain: a genetic animal model of absence epilepsy with comorbidity
      of depression [corrected].
AB  - A great number of clinical observations show a relationship between epilepsy and
      depression. Idiopathic generalized epilepsy, including absence epilepsy, has a
      genetic basis. The review provides evidence that WAG/Rij rats can be regarded as
      a valid genetic animal model of absence epilepsy with comorbidity of depression.
      WAG/Rij rats, originally developed as an animal model of human absence epilepsy,
      share many EEG and behavioral characteristics resembling absence epilepsy in
      humans, including the similarity of action of various antiepileptic drugs.
      Behavioral studies indicate that WAG/Rij rats exhibit depression-like symptoms:
      decreased investigative activity in the open field test, increased immobility in
      the forced swimming test, and decreased sucrose consumption and preference
      (anhedonia). In addition, WAG/Rij rats adopt passive strategies in stressful
      situations, express some cognitive disturbances (reduced long-term memory),
      helplessness, and submissiveness, inability to make choice and overcome
      obstacles, which are typical for depressed patients. Elevated anxiety is not a
      characteristic (specific) feature of WAG/Rij rats; it is a characteristic for
      only a sub-strain of WAG/Rij rats susceptible to audiogenic seizures.
      Interestingly, WAG/Rij rats display a hyper-response to amphetamine similar to
      anhedonic depressed patients. WAG/Rij rats are sensitive only to chronic, but not
      acute, antidepressant treatments, suggesting that WAG/Rij rats fulfill a
      criterion of predictive validity for a putative animal model of depression.
      However, more and different antidepressant drugs still await evaluation.
      Depression-like behavioral symptoms in WAG/Rij rats are evident at baseline
      conditions, not exclusively after stress. Experiments with foot-shock stress do
      not point towards higher stress sensitivity at both behavioral and hormonal
      levels. However, freezing behavior (coping deficits) and blunted response of 5HT
      in the frontal cortex to uncontrollable sound stress, increased c-fos expression
      in the terminal regions of the meso-cortico-limbic brain systems and greater DA
      response of the mesolimbic system to forced swim stress suggest that WAG/Rij rats
      are vulnerable to some, but not to all types of stressors. We propose that
      genetic absence epileptic WAG/Rij rats have behavioral depression-like symptoms,
      are vulnerable to stress and might represent a model of chronic low-grade
      depression (dysthymia). Both 5HT and DAergic abnormalities detected in the brain
      of WAG/Rij rats are involved in modulation of vulnerability to stress and
      provocation of behavioral depression-like symptoms. The same neurotransmitter
      systems modulate SWDs as well. Recent studies suggest that the occurrence and
      repetition of absence seizures are a precipitant of depression-like behavior.
      Whether the neurochemical changes are primary to depression-like behavioral
      alterations remains to be determined. In conclusion, the WAG/Rij rats can be
      considered as a genetic animal model for absence epilepsy with comorbidity of
      dysthymia. This model can be used to investigate etiology, pathogenic mechanisms
      and treatment of a psychiatric comorbidity, such as depression in absence
      epilepsy, to reveal putative genes contributing to comorbid depressive disorder,
      and to screen novel psychotropic drugs with a selective and/or complex (dual)
      action on both pathologies.

PMID- 21093522
TI  - Chemical composition and antioxidant activity of essential oils and solvent
      extracts of Ptychotis verticillata from Morocco.
AB  - The objective of this study was to characterize the chemical composition of the
      essential oil and extracts of Ptychotis verticillata. The antioxidative
      activities of this species were also evaluated to suggest it as a new potential
      source of natural antioxidants. Analysis of the chemical composition of P.
      verticillata essential oil from Morocco was carried out using GC and GC-MS. The
      oil was dominated by phenolic compounds (48.0%) with carvacrol (44.6%) and thymol
      (3.4%) as the main compounds. Plant phenolics constitute one of the major groups
      of components that act as primary antioxidant free radical terminators. The
      amounts of total phenolics and flavonoids in the solvent extracts (diethyl ether
      and ethyl acetate) were determined spectrometrically. Furthermore, the
      antioxidant activities of the essential oil and extracts were determined using a
      DPPH test system. The DPPH scavenging activity of extracts increased in the order
      ethyl acetate>ascorbic acid>diethyl ether>essential oil. Finally, a relationship
      was observed between the antioxidant activity potential and total phenolic and
      flavonoid levels of the extract.

PMID- 21093523
TI  - A 90-day subchronic toxicological assessment of Antrodia cinnamomea in Sprague
      Dawley rats.
AB  - Antrodia cinnamomea (Ac) is a medicinal mushroom widely used for the treatment of
      abdominal pain, hypertension and hepatocellular carcinoma, but subchronic
      toxicity of this material has not yet been investigated. This present study was
      conducted to assess the 90-day oral toxicity of A. cinnamomea from submerged
      culture in male and female Sprague-Dawley (SD) rats. Eighty rats were divided
      into four groups, each consisting of ten male and ten female rats. Test articles
      were administered by oral gavage to rats at 3000, 2200 and 1500 mg/kg BW/day for
      90 consecutive days and reverse osmosis water was used as control. All animals
      survived to the end of the study. During the experiment period, no abnormal
      changes were observed in clinical signs, body weight and ophthalmological
      examinations. No significant differences were found in urinalysis, hematology and
      serum biochemistry parameters between the treatment and control groups. Necropsy
      and histopathological examination indicated no treatment-related changes.
      According to the above results, the no-observed-adverse-effect level (NOAEL) of
      Antrodia cinnamomea is identified to be greater than 3000 mg/kg BW/day in Sprague
      Dawley rats.

PMID- 21093524
TI  - Diverse role of microbially bioconverted product of cabbage (Brassica oleracea)
      by Pseudomonas syringe pv. T1 on inhibiting Candida species.
AB  - This study was carried out to evaluate the anticandidal effects of bioconverted
      product, obtained from the microbial conversion of cabbage (Brassica oleracea) by
      a bacterial strain Pseudomonas syringe pv. T1 (Ps-T1) against various isolates of
      Candida species. The diameters of zones of inhibition of bioconverted product of
      cabbage (10 MUl, corresponding to 500 MUg/disc) against Candida albicans KACC
      30003 and 30062, Candida geochares KACC 30061, Candida saitoana KACC 41238 and
      Candida glabrata P00368 were found between 10+/-1 and 16+/-0.8 mm. The
      bioconverted product was tested for the minimum inhibitory and minimum fungicidal
      concentration values against the tested pathogens which were found in the range
      of 125-500 and 125-500 MUg/ml, respectively. On the viable counts of the tested
      fungal pathogens, the bioconverted product showed a remarkable anticandidal
      effect. Also the study of using scanning electron microscopy on the morphology of
      C.albicans KACC 30062 revealed potential detrimental effect of bioconverted
      product at MIC concentration. The results of this study suggest that bioconverted
      product of cabbage by Ps-T1 holds potential therapeutic value and medicinal
      significance to control Candida species.

PMID- 21093525
TI  - European consumer exposure to cosmetic products, a framework for conducting
      population exposure assessments Part 2.
AB  - Access to reliable exposure data is essential for the evaluation of the
      toxicological safety of ingredients in cosmetic products. This study complements
      the data set obtained previously (Part 1) and published in 2007 by the European
      cosmetic industry acting within COLIPA. It provides, in distribution form,
      exposure data on daily quantities of five cosmetic product types: hair styling,
      hand cream, liquid foundation, mouthwash and shower gel. In total 80,000
      households and 14,413 individual consumers in five European countries provided
      information using their own products. The raw data were analysed using Monte
      Carlo simulation and a European Statistical Population Model of exposure was
      constructed. A significant finding was an inverse correlation between the
      frequency of product use and the quantity used per application recorded for
      mouthwash and shower gel. The combined results of Part 1 (7 product types) and
      Part 2 (5 products) reported here, bring up to date and largely confirm the
      current exposure parameters concerning some 95% of the estimated daily exposure
      to cosmetics use in the EU. The design of this study, with its relation to
      demographic and individual diversity, could serve as a model for studies of
      populations' exposure to other consumer products.

PMID- 21093527
TI  - How strong is the evidence for the need to restore posterior bounded edentulous
      spaces in adults? Grading the quality of evidence and the strength of
      recommendations.
AB  - BACKGROUND: It is unclear whether or not untreated bounded edentulous spaces
      (BES) can cause patients problems because of migration of unopposed and adjacent
      teeth. OBJECTIVES: To quantitatively assess BES-related occlusal changes and the
      level of evidence available. MATERIAL AND METHODS: A systematic search of the
      literature was conducted in triplicate in the PubMed and Cochrane Register of
      Controlled Trials (CENTRAL) databases up to and including February 2010 to assess
      studies related to the topic. The LILACS database also was searched by one of the
      authors (CMF). Quantitative mesio-distal changes and overeruption were the
      outcome measures. Manual searching of the reference lists of studies retrieved
      from the electronic databases was also conducted. Google Scholar in English,
      French, German, Greek, Italian, Portuguese, and Spanish was also searched to
      retrieve potential studies. Grey literature was searched in OpenSIGLE (System for
      Information on Grey Literature in Europe) for more potential papers. The quality
      of the retrieved literature and the strength of recommendations were assessed by
      use of the GRADE system. A decision-tree-like scheme was produced to depict
      treatment options. RESULTS: The available evidence demonstrated that for most
      cases occlusal changes in BES after tooth loss might be limited (on average up to
      2mm). The quality of evidence was regarded as very low, however. CONCLUSIONS:
      Tooth replacement should not necessarily be regarded as the mainstay of therapy
      for posterior BES, although more robust studies are necessary to clarify the long
      term effects of non-treatment. The GRADE approach may be useful for enhancing the
      transparency of the decision-making process in dentistry, especially when
      evidence of only limited quality is available.

PMID- 21093526
TI  - Analysis of the passage of the marine biotoxin okadaic acid through an in vitro
      human gut barrier.
AB  - The marine biotoxin okadaic acid (OA), produced by dinoflagellates, can
      accumulate in various bivalve molluscs. In humans, oral consumption of shellfish
      contaminated with OA induces acute toxic effects like diarrhea, nausea, vomiting
      and abdominal pain. However, tumorigenic and embryotoxic effects of OA have been
      also described. Current toxicokinetic studies with mice were performed with high
      cytotoxic oral doses leading presumably to a paracellular passage of OA through
      the gastrointestinal barrier. There are no studies available analyzing the
      absorption at low concentrations, which represent a realistic dietary exposure,
      making a reliable risk assessment difficult. Therefore, we performed a low-dose
      study using the human intestinal Caco-2 cell model to simulate the intestinal
      barrier. Low level exposure of 20-200 nM OA to the cell monolayer allows an only
      limited passage from the "luminal" to the "blood side". Furthermore, we could
      detect a significant efflux of OA, which led to the suggestion that active
      transport mechanisms are involved in the elimination process of OA. In
      conclusion, our results indicate that besides the well known defense mechanisms
      of humans against this marine biotoxin--vomiting and diarrhea--further
      detoxification mechanisms are available to limit the absorption of toxic OA.

PMID- 21093528
TI  - Disinfection procedures: their efficacy and effect on dimensional accuracy and
      surface quality of an irreversible hydrocolloid impression material.
AB  - OBJECTIVES: This study investigated the antibacterial efficacy and effect of
      0.55% ortho-phthalaldehyde (Cidex OPA((r))) and 0.5% sodium hypochlorite (NaOCl)
      on the dimensional accuracy and surface quality of gypsum casts retrieved from an
      irreversible hydrocolloid impression material. METHODS: A simulated clinical cast
      and technique was developed to compare the dimensional accuracy and surface
      quality changes of the test gypsum casts with controls. Dimensional accuracy
      measurements were completed between fixed points using a travelling microscope
      under low angle illumination at a magnification of *3. Surface quality changes of
      "smooth" and "rough" areas on the cast were evaluated by means of optical
      profilometry. The efficacy of the disinfection procedures against Pseudomonas
      aeruginosa was evaluated by determining the number of colony forming units (cfu)
      recovered after disinfection of alginate discs inoculated with 1*106cfu for
      defined intervals. RESULTS: The dimensional accuracy of the gypsum casts was not
      significantly affected by the disinfection protocols. Neither disinfectant
      solution nor immersion time had an effect on the surface roughness of the
      "smooth" area on the cast, however, a significant increase in surface roughness
      was observed with increasing immersion time for the "rough" surface. Complete
      elimination of viable Pseudomonas aeruginosa cells from alginate discs was
      obtained after 30 and 120 s immersion in Cidex OPA((r)) and NaOCl, respectively.
      CONCLUSIONS: Immersion of irreversible hydrocolloid impressions in Cidex OPA((r))
      for 30 s was proved to be the most effective disinfection procedure.

PMID- 21093530
TI  - Nonemotional features suppress early and enhance late emotional electrocortical
      responses to negative pictures.
AB  - Neural processing of emotional pictures is often indexed by two electrocortical
      responses: the early posterior negativity (EPN) and the late positive potential
      (LPP). Because emotional pictures vary in nonemotional features (e.g.,
      composition, human content, and spatial frequency), researchers often match
      pictures on nonemotional features to avoid their confounding effects on the EPN
      and LPP. However, this matching is tedious and might be unnecessary if the
      confounding effects could be shown to be negligible. In an item-analysis of mean
      amplitudes to 400 negative to neutral pictures from the International Affective
      Picture System (IAPS), nonemotional features had larger effects on EPN than LPP.
      Picture composition suppressed the relationship between emotion and EPN. Further,
      data simulations showed that for small picture sets, nonemotional features
      inflated the correlation between emotion and LPP. Therefore, nonemotional
      features suppress the EPN and enhance the LPP, particularly so in small picture
      sets.

PMID- 21093531
TI  - Event-related potential correlates of the expectancy violation effect during
      emotional prosody processing.
AB  - The present study investigated the expectancy violation effects evoked by
      deviation in sentential emotional prosody (EP), and their association with the
      deviation patterns. Event-related potentials (ERPs) were recorded for mismatching
      EPs with different patterns of deviation and for matching control EPs while
      subjects performed emotional congruousness judgment in Experiment 1 and visual
      probe detection tasks in Experiment 2. In the control experiment, EPs and
      acoustically matched non-emotional materials were presented and ERPs were
      recorded while participants judged the sound intensity congruousness. It was
      found that an early negativity, whose peak latency varied with deviation pattern,
      was elicited by mismatching EPs relative to matching ones, irrespective of task
      relevance. A late positivity was specifically induced by mismatching EPs, and was
      modulated by both deviation pattern and task-relevance. Moreover, these effects
      cannot be simply attributed to the change in non-emotional acoustic properties.
      These findings suggest that the brain detects the EP deviation rapidly, and then
      integrates it with context for comprehension, during which the emotionality plays
      a role of speeding up the perception and enhancing vigilance.

PMID- 21093529
TI  - Neuronal control of swimming behavior: comparison of vertebrate and invertebrate
      model systems.
AB  - Swimming movements in the leech and lamprey are highly analogous, and lack
      homology. Thus, similarities in mechanisms must arise from convergent evolution
      rather than from common ancestry. Despite over 40 years of parallel
      investigations into this annelid and primitive vertebrate, a close comparison of
      the approaches and results of this research is lacking. The present review
      evaluates the neural mechanisms underlying swimming in these two animals and
      describes the many similarities that provide intriguing examples of convergent
      evolution. Specifically, we discuss swim initiation, maintenance and termination,
      isolated nervous system preparations, neural-circuitry, central oscillators,
      intersegmental coupling, phase lags, cycle periods and sensory feedback.
      Comparative studies between species highlight mechanisms that optimize behavior
      and allow us a broader understanding of nervous system function.

PMID- 21093532
TI  - Odor perception between heterosexual partners: its association with depression,
      anxiety, and genetic variation in odorant receptor OR7D4.
AB  - We performed a study on a sample of 856 individuals to answer whether the
      pleasantness/unpleasantness of the odor perception of their partners (rating of
      partner odor) is associated with depression and anxiety. To evaluate the
      influence of common genetic variation of the odorant receptor OR7D4 on the rating
      of partner odor, the variant rs8109935 was genotyped in the whole sample. The
      rating of partner odor was significantly associated with scores of anxiety and
      depression. Depression (OR: 0.75, 95% CI: 0.56-0.98, p = 0.039) and anxiety
      (Robust Coef +/- SE: -13 +/- 0.6, p = 0.044) were inversely associated with
      pleasantness rating of partner odor. Ordered probit regression analysis shows
      that the rating of partner odor was significantly associated with the rs8109935
      genotypes (Coef +/- robust SE: 0.19 +/- 0.09, p = 0.028). These findings suggest
      that odor perception between heterosexual partners may have an impact on the
      development of depression and anxiety, and that it might be influenced by genetic
      variation in OR7D4.

PMID- 21093533
TI  - Regulation and deregulation of mRNA translation during myeloid maturation.
AB  - Gene expression in the eukaryotic cell is regulated at a number of levels,
      including transcription of genomic DNA into messenger RNA (mRNA),
      nucleocytoplasmic export of mRNA, and translation of the exported mRNA into
      proteins in the cytoplasm by ribosomes. The role played by epigenetics and
      transcription factors associated with the control of gene expression in the
      developing neutrophil has been well documented and appreciated over the years. A
      wealth of information on the role played by transcription factors in myeloid
      biology has contributed to our understanding of both normal and abnormal
      neutrophil development. However, regulation of mRNA translation in myeloid cell
      maturation is much less well-studied. A better understanding of the translational
      control of myeloid gene expression may provide important insights into both
      normal and abnormal myeloid maturation. This review summarizes our current
      understanding of the regulation of myeloid gene expression at the mRNA
      translational level.

PMID- 21093534
TI  - Special issue: computational models in photosynthesis.

PMID- 21093535
TI  - The single-process biochemical reaction of Rubisco: a unified theory and model
      with the effects of irradiance, CO2 and rate-limiting step on the kinetics of C3
      and C4 photosynthesis from gas exchange.
AB  - Photosynthesis is the origin of oxygenic life on the planet, and its models are
      the core of all models of plant biology, agriculture, environmental quality and
      global climate change. A theory is presented here, based on single process
      biochemical reactions of Rubisco, recognizing that: In the light, Rubisco
      activase helps separate Rubisco from the stored ribulose-1,5-bisphosphate (RuBP),
      activates Rubisco with carbamylation and addition of Mg2(+), and then produces
      two products, in two steps: (Step 1) Reaction of Rubisco with RuBP produces a
      Rubisco-enediol complex, which is the carboxylase-oxygenase enzyme (Enco) and
      (Step 2) Enco captures CO2 and/or O2 and produces intermediate products leading
      to production and release of 3-phosphoglycerate (PGA) and Rubisco. PGA
      interactively controls (1) the carboxylation-oxygenation, (2) electron transport,
      and (3) triosephosphate pathway of the Calvin-Benson cycle that leads to the
      release of glucose and regeneration of RuBP. Initially, the total enzyme
      participates in the two steps of the reaction transitionally and its rate follows
      Michaelis-Menten kinetics. But, for a continuous steady state, Rubisco must be
      divided into two concurrently active segments for the two steps. This causes a
      deviation of the steady state from the transitional rate. Kinetic models are
      developed that integrate the transitional and the steady state reactions. They
      are tested and successfully validated with verifiable experimental data. The
      single-process theory is compared to the widely used two-process theory of
      Farquhar et al. (1980. Planta 149, 78-90), which assumes that the carboxylation
      rate is either Rubisco-limited at low CO2 levels such as CO2 compensation point,
      or RuBP regeneration-limited at high CO2. Since the photosynthesis rate cannot
      increase beyond the two-process theory's Rubisco limit at the CO2 compensation
      point, net photosynthesis cannot increase above zero in daylight, and since there
      is always respiration at night, it leads to progressively negative daily CO2
      fixation with no possibility of oxygenic life on the planet. The Rubisco-limited
      theory at low CO2 also contradicts all experimental evidence for low substrate
      reactions, and for all known enzymes, Rubisco included.

PMID- 21093536
TI  - Follow up estimation of Aedes aegypti entomological parameters and mathematical
      modellings.
AB  - The dengue virus is a vector-borne disease transmitted by mosquito Aedes aegypti
      and the incidence is strongly influenced by temperature and humidity which vary
      seasonally. To assess the effects of temperature on dengue transmission,
      mathematical models are developed based on the population dynamics theory.
      However, depending on the hypotheses of the modelling, different outcomes
      regarding to the risk of epidemics are obtained. We address this question
      comparing two simple models supplied with model's parameters estimated from
      temperature-controlled experiments, especially the entomological parameters
      regarded to the mosquito's life cycle in different temperatures. Once obtained
      the mortality and transition rates of different stages comprising the life cycle
      of mosquito and the oviposition rate, we compare the capacity of vector
      reproduction (the basic offspring number) and the risk of infection (basic
      reproduction number) provided by two models. The extended model, which is more
      realistic, showed that both mosquito population and dengue risk are situated at
      higher values than the simplified model, even that the basic offspring number is
      lower.

PMID- 21093537
TI  - Individual-based modelling of angiogenesis inside three-dimensional porous
      biomaterials.
AB  - This paper presents a simulation modelling framework to study the growth of blood
      vessels and cells through a porous tissue engineering scaffold. The model
      simulates the migration of capillaries and the formation of a vascular network
      through a single pore of a tissue engineering scaffold when it is embedded in
      living tissue. The model also describes how the flow of blood through the network
      changes as growth proceeds. Results are given for how the different strategies of
      seeding the pore with cells affects the extent of vascularisation. Also
      simulations are made to compare results where the values of different model
      parameters are varied such as the pore dimensions, the density of endothelial
      cells seeded into the pore, and the release rate of growth factor from the
      scaffold into the pore. The modelling framework described in this paper is useful
      for exploring experimental strategies for producing well-vascularised tissue
      engineered constructs, and is therefore potentially important to the field of
      regenerative medicine.

PMID- 21093538
TI  - How occasional backstepping can speed up a processive motor protein.
AB  - Fueled by the hydrolysis of ATP, the motor protein kinesin literally walks on two
      legs along the biopolymer microtubule. The number of accidental backsteps that
      kinesin takes appears to be much larger than what one would expect given the
      amount of free energy that ATP hydrolysis makes available. This indicates that
      backsteps are not simply the forward stepping cycle run backwards. We propose
      here a simple effective model that consistently includes the backstep transition.
      Using this model, we show how more backstepping increases the entropy of the
      final state, and probably also the activation state, thus reducing their free
      energy. This free energy reduction of the activation state (related to
      backstepping) speeds up the catalytic cycle of the kinesin, making both forward
      and backward steps more frequent. As a consequence, maximal net forward speed is
      achieved at nonzero backstep percentage. In addition, the optimal backstep
      percentage coincides with the backstep percentage measured for kinesin. This
      result suggests that, through natural selection, kinesin could have evolved to
      maximal speed.

PMID- 21093539
TI  - Goldfish brain somatostatin-28 differentially affects dopamine- and pituitary
      adenylate cyclase-activating polypeptide-induced GH release and Ca(2+) and cAMP
      signals.
AB  - Dopamine (DA) and pituitary adenylate cyclase-activating polypeptide (PACAP)
      stimulate goldfish growth hormone (GH) release via cAMP- and Ca(2+)-dependent
      pathways while DA also utilizes NO. In this study, identified goldfish
      somatotropes responded to sequential applications of PACAP and the DA D1 agonist
      SKF38393 with increased intracellular Ca(2+) levels ([Ca(2+)](i)), indicating
      that PACAP and DA D1 receptors were present on the same cell. A native goldfish
      brain somatostatin (gbSS-28) reduced SKF38393-stimulated cAMP production and
      PACAP- and NO donor-elicited GH and [Ca(2+)](i) increases, but not PACAP-induced
      cAMP production nor the GH and [Ca(2+)](i) responses to forskolin, 8-bromo-cAMP
      and SKF38393. gbSS-28 might inhibit PACAP-induced GH release by interfering with
      PACAP's ability to increase [Ca(2+)](i) in a non-cAMP-dependent manner. However,
      DA D1 receptor activation bypassed gbSS-28 inhibitory effects on cAMP production
      and NO actions via unknown mechanisms to maintain a normal [Ca(2+)](i) response
      leading to unhampered GH release.

PMID- 21093540
TI  - Inhibition of ganglioside synthesis reduces the neuronal survival activity of
      astrocytes.
AB  - Gangliosides are sialic acid-containing sphingolipids that have promoting effects
      on the survival, growth, and functions of neurons in the central nervous system.
      Glial cells including astrocytes assist neurons with regard to their
      proliferation, maintenance, and function. In the present study, we found that
      astrocytes with ganglioside depletion caused by treatment with d-threo-1-phenyl-1
      2-decanoylamino-3-morpholino-1-propanol (d-PDMP) exhibited reduced neuronal
      survival activity, as evaluated using low-density hippocampal cultures. The
      reduction was rescued by a ganglioside, GM3, suggesting that GM3 has significant
      effects on the glial cell activities that help neurons to proliferate and be
      maintained.

PMID- 21093541
TI  - Immunolocalization of membrane skeletal protein, 4.1G, in enteric glial cells in
      the mouse large intestine.
AB  - 4.1 family proteins are membrane skeletal proteins that interact with spectrin
      actin networks and intramembraneous proteins. We reported that one of them, 4.1G,
      was immunolocalized in myelinated nerve fibers of the mouse peripheral nervous
      system, especially along cell membranes of paranodes and Schmidt-Lanterman
      incisures in Schwann cells. In this study, to examine 4.1G's appearance in
      unmyelinated peripheral nerve fibers, we focused on the enteric nervous system in
      mouse large intestines. In intestinal tissues prepared by an "in vivo
      cryotechnique" followed by freeze-substitution fixation, 4.1G was immunolocalized
      in Auerbach's myenteric plexus and connecting nerve fiber networks. Its
      immunostaining was mostly colocalized with glial fibrillar acidic protein, a
      marker of enteric glial cells, but not with c-Kit, a marker of interstitial cells
      of Cajal. Using whole-mount preparation after splitting inner and outer muscle
      layers, the nerve fiber networks including the plexus were clearly detected by
      the 4.1G immunostaining. By conventional pre-embedding immunoelectron microscopy,
      4.1G was detected along cell membranes of enteric glial cells and their processes
      surrounding axons. These indicate that 4.1G may have some roles in adhesion
      and/or signal transduction in unmylinated PNS nerve fibers.

PMID- 21093542
TI  - Substance P in the cerebrospinal fluid-contacting nucleus contributes to morphine
      physical dependence in rats.
AB  - The cerebrospinal fluid-contacting nucleus (CSF-CN), distributes and localizes in
      the ventral periaqueductal central gray (PAG) of the brainstem, which may
      influence actual composition of the cerebrospinal fluid (CSF) for non-synaptic
      signal transmission via releasing or absorbing bioactive substances. Many
      experiments have demonstrated that substance P (SP), a substance that is shown to
      be up-regulated in CSF-CN, plays an important role in the development of
      inflammatory pain and neuropathic pain. Thus in the present study, we hypothesize
      that SP in CSF-CN might contribute to morphine dependence in rats, inhibiting SP
      with (D-Pro2, D-Phe7, D-Trp9)-SP intracerebroventricular (i.c.v.) injection
      reduce chronic morphine dependence and withdrawal. Rats were repeatedly injected
      with morphine in five escalating doses for morphine physical dependence. Morphine
      withdrawal-like behavioral signs and morphine analgesia behaviors were monitored
      after naloxone administration following i.c.v. injection of (D-Pro2, D-Phe7, D
      Trp9)-SP. And SP-expression of CSF-CN was evaluated with dual-label
      immunofluorescent technique on morphine withdrawal in rats. After i.c.v.
      treatment with (D-Pro2, D-Phe7, D-Trp9)-SP, the naloxone-precipitated withdrawal
      symptoms were significantly attenuated, paw withdrawal threshold/thermal
      withdrawal latency (PWT/TWL) were increased, and SP-expression in CSF-CN was
      significantly reduced than control group. SP, known a
      neurotransmitter/neuromodulator of nociception, has also been implicated in the
      signs of opioid withdrawal. This study provides the first evidence that SP in CSF
      CN contributes to morphine physical dependence and withdrawal, which may provide
      an important and specific role in mediating the motivational aspects of opiates
      withdrawal via CSF - the parenchyma of the brain, and may represent a novel
      pharmacological route such as SP inhibitor i.c.v. injection for the control of
      drug abuse.

PMID- 21093543
TI  - Lamotrigine blocks apoptosis induced by repeated administration of high-dose
      methamphetamine in the medial prefrontal cortex of rats.
AB  - Lamotrigine (LTG) is sometimes co-administered with antipsychotic drugs for the
      treatment of schizophrenia. Nevertheless, the pharmacological basis of LTG use
      for schizophrenia has not been reported. Our group recently proposed a new
      psychostimulant animal model that might reflect the progressive pathophysiology
      of schizophrenia. Results obtained using that model show that LTG blocks the
      initiation and expression of repeated high-dosage methamphetamine-induced
      prepulse inhibition deficit in rats (Nakato et al., 2010, Neurosci. Lett. [25]).
      Using the model, the effect of LTG (30 mg/kg) on methamphetamine (METH, 2.5
      mg/kg)-induced increases in extracellular glutamate levels in the medial
      prefrontal cortex (mPFC) was examined in this study. Then the effect of repeated
      co-administration of LTG (30 mg/kg) on repeated METH (2.5 mg/kg)-induced
      apoptosis in this region of rats was investigated. Results show that LTG (30
      mg/kg) blocked the METH (2.5 mg/kg)-induced glutamate increase in the mPFC.
      Repeated co-administration of LTG (30 mg/kg) blocked the development of apoptosis
      induced by repeated administration of METH (2.5 mg/kg) in the mPFC. The LTG
      blocks histological abnormalities induced by repeated administration of METH,
      which suggests a mechanism of LTG that protects against progressive
      pathophysiology in schizophrenia.

PMID- 21093544
TI  - Local repeated corticotropin-releasing factor infusion exacerbates anxiety- and
      fear-related behavior: differential involvement of the basolateral amygdala and
      medial prefrontal cortex.
AB  - Increased central corticotropin-releasing factor (CRF) signaling has been
      associated with various psychiatric symptoms, including anxiety, depression and
      psychosis. CRF signaling in both the basolateral amygdala (BLA) and medial
      prefrontal cortex (mPFC) has been implicated in anxiety-like behavior. In
      addition, repeated activation of CRF receptors within the BLA induces a chronic
      anxious state. Here we studied the effects of local repeated CRF infusion in the
      BLA and mPFC on different forms of anxiety, as assessed during light-enhanced
      startle (LES, general anxiety) and acquisition of fear-potentiated startle (FPS,
      cue-conditioned fear). In addition, as CRF has been implicated in sensorimotor
      gating, prepulse inhibition (PPI) was assessed to determine if local CRF infusion
      within the BLA or mPFC would interfere with the processing of sensory
      information. To this end, canulas were placed bilaterally in either the BLA or
      mPFC of Wistar rats. After recovery, animals were infused with h/rCRF (200
      ng/side) or vehicle for five consecutive days. Long term effects of local CRF
      infusion on LES and acquisition of FPS were measured 4 and 10 days post
      treatment, respectively. In addition, the acute (day 1), sub-chronic (day 5) and
      long-term (7 days post treatment) effects on PPI were measured in the same
      animals. A clear regional differentiation was found on the long lasting effect of
      CRF on anxiety-like behavior: infusion into the BLA only enhanced acquisition of
      FPS, whereas infusion into the mPFC only enhanced LES. Sub-chronic CRF infusion
      into the BLA, but not the mPFC, disrupted PPI. This disturbed PPI was normalized
      7 days post-treatment. Together, the current study shows that local repeated CRF
      receptor activation in the BLA and mPFC is differentially involved in anxiety-
      and fear-related behavior. In addition, the BLA may be involved in CRF-induced
      sensorimotor gating deficits. The absence of a long-term effect on these PPI
      deficits suggests that lasting activation of CRF receptors is a prerequisite for
      CRF-mediated effects on sensorimotor gating. The long-term effects of repeated
      CRF infusion on LES and acquisition of FPS on the other hand, show that in case
      of anxiety-related processes repeated CRF infusion may have lasting effects.

PMID- 21093545
TI  - Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque
      formation in Tg2576 mice.
AB  - A mouse model of amyloid pathology was used to first examine using a cross
      sectional design changes in retrosplenial cortex activity in transgenic mice aged
      5, 11, 17, and 23 months. Attention focused on: (1) overt amyloid labeled with
      beta-amyloid((1-42)) and Congo Red staining, (2) metabolic function assessed by
      the enzyme, cytochrome oxidase, and (3) neuronal activity as assessed indirectly
      by the immediate-early gene (IEG), c-Fos. Changes in cytochrome oxidase and c-Fos
      activity were observed in the retrosplenial cortex in Tg2576 mice as early as 5
      months of age, long before evidence of plaque formation. Subsequent analyses
      concentrating on this early dysfunction revealed at 5 months pervasive, amyloid
      precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex
      and selective afferents (anterior thalamus, hippocampus), which was associated
      with the observed c-Fos hyporeactivity. These findings indicate that
      retrosplenial cortex dysfunction occurs during early stages of amyloid production
      in Tg2576 mice and may contribute to cognitive dysfunction.

PMID- 21093547
TI  - Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and
      amygdala long-term potentiation.
AB  - Complex brain diseases and neurological disorders in human generally result from
      the disturbance of multiple genes and signaling pathways. These disturbances may
      derive from mutations, deletions, translocations or rearrangements of specific
      gene(s). However, over the past years, it has become clear that such disturbances
      may also derive from alterations in the epigenome affecting several genes
      simultaneously. Our work recently demonstrated that epigenetic mechanisms in the
      adult brain are in part regulated by protein phosphatase 1 (PP1), a protein
      Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term
      memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures
      involved in emotional processing like the amygdala, it may therefore be involved
      in the regulation of fear memory, a form of memory related to post-traumatic
      stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular
      suppressor of fear memory and synaptic plasticity in the amygdala that can
      control chromatin remodeling in neurons. We show that the selective inhibition of
      the nuclear pool of PP1 in amygdala neurons significantly alters
      posttranslational modifications (PTMs) of histones and the expression of several
      memory-associated genes. These alterations correlate with enhanced fear memory,
      and with an increase in long-term potentiation (LTP) that is transcription
      dependent. Our results underscore the importance of nuclear PP1 in the amygdala
      as an epigenetic regulator of emotional memory, and the relevance of protein
      phosphatases as potential targets for therapeutic treatment of brain disorders
      like PTSD.

PMID- 21093548
TI  - Representation of the bird's own song in the canary HVC: contribution of broadly
      tuned neurons.
AB  - In songbirds, neurons in the song nucleus HVC exhibit a striking example of
      selective auditory response, firing more to playback of the bird's own song (BOS)
      than to conspecific songs. This song selectivity has been found in various
      songbird species, both those that sing a single individual-specific song as well
      as those, such as the canary, in which both song structure and individual
      identity encoding in song is more complex. In the present study, we investigated
      how the BOS is represented in the HVC of anesthetized long-day canaries by using
      temporal and spectral variants of the BOS stimulus. We addressed the question of
      how selective HVC neurons were by quantifying the number of song elements, called
      phrases, that evoked auditory responses. Phrases that were individual-specific or
      that were frequently delivered in an individual's songs did not drive HVC neurons
      to a greater degree than others. Reordering phrases or altering their acoustic
      structure caused a decrease in the auditory responsiveness of HVC neurons. This
      sensitivity to the spectral and temporal features of the BOS involved neurons
      that failed to respond to BOS variants or were driven by a reduced number of
      phrases, as well as neurons whose auditory responsiveness extended beyond the
      features of the individual's song, responding to phrases that were not sung by
      the bird itself. Therefore, the neural strategy by which BOS structure is
      represented in the canary HVC may require something other than a strict
      representation of the repertoire of song components. We suggest that the
      individual's song could be coded, at least in part, by an ensemble of broadly
      tuned neurons.

PMID- 21093546
TI  - Characterization of Kiss1 neurons using transgenic mouse models.
AB  - Humans and mice with loss-of-function mutations of the genes encoding kisspeptins
      (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic
      hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the
      anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In
      order to better study the different populations of kisspeptin cells we generated
      Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically
      within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre
      dependent expression of green fluorescent protein or beta-galactosidase. Also, we
      demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data
      showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic
      nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the
      Arc and higher leptin-responsivity was observed in the most caudal population of
      Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons
      was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the
      preoptic area and Arc, and both populations expressed melanocortin receptors type
      4 (MC4R). Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed
      MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were
      GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were
      GABAergic. The differences observed between the Kiss1 neurons in the preoptic
      area and the Arc likely represent neuronal evidence for their differential roles
      in metabolism and reproduction.

PMID- 21093549
TI  - Pancreatitis-associated protein-I and pancreatitis-associated protein-III
      expression in a rat model of kainic acid-induced seizure.
AB  - The pancreatitis-associated protein (PAP) family (also known as the regenerating
      gene (Reg) family) is a group of 16 kDa secretory proteins structurally
      classified as the calcium dependent-type lectin superfamily. Some PAP family
      members are expressed in neurons following peripheral nerve injury and traumatic
      brain injury. To determine whether PAP family members are expressed in non
      traumatic brain injury, expressions were analyzed following kainic acid (KA)
      induced seizure. PAP-I (also known as Reg2 in rat and RegIII-beta in mouse) and
      pancreatitis associated protein-III (PAP-III; RegIII-gamma in mouse) messenger
      ribonucleic acid (mRNA) was transiently expressed in some restricted areas, such
      as the hippocampus and parahippocampal area; expression was observed immediately
      at a maximal level 1 day after seizure. Expression disappeared within 3 days
      after seizure. In situ hybridization (ISH) and immunohistochemistry revealed
      neuronal PAP-I and PAP-III expression in the hippocampal dentate gyrus,
      perirhinal and entorhinal cortices, and the posterior cortical nucleus of the
      amygdala. The number of PAP-III mRNA-positive neurons was significantly greater
      than PAP-I mRNA-positive neurons. The majority of positive neurons co-localized
      with c-Jun, but not with glutamic acid decarboxylase (GAD). These results may
      suggest that PAP-I and PAP-III induction in non-GABAergic neurons would protect
      neurons against damage following seizure.

PMID- 21093550
TI  - Task-dependent differences in corticobulbar excitability of the submental motor
      projections: Implications for neural control of swallowing.
AB  - It has been suggested that the primary motor cortex plays a substantial role in
      the neural circuitry that controls swallowing. Although its role in the voluntary
      oral phase of swallowing is undisputed, its precise role in motor control of the
      more reflexive, pharyngeal phase of swallowing is unclear. The contribution of
      the primary motor cortex to the pharyngeal phase of swallowing was examined using
      transcranial magnetic stimulation (TMS) to evoke motor evoked potentials (MEPs)
      in the anterior hyomandibular muscle group during either volitional submental
      muscle contraction or contraction during the pharyngeal phase of both
      volitionally, and reflexively, initiated swallowing. For each subject, in all
      three conditions, TMS was triggered when submental surface EMG (sEMG) reached 75%
      of the mean maximal submental sEMG amplitude measured during 10 volitional
      swallows. MEPs recorded during volitional submental muscle contraction were
      elicited in 22 of the 35 healthy subjects examined (63%). Only 16 of these 22
      subjects (45.7%) also displayed MEPs recorded during volitional swallowing, but
      their MEP amplitudes were larger when triggered by submental muscle contraction
      than when triggered by volitional swallowing. Additionally, only 7 subjects (of
      19 tested) showed MEPs triggered by submental muscle contraction during a
      reflexively triggered pharyngeal swallow. These differences indicate differing
      levels of net M1 excitability during execution of the investigated tasks,
      possibly brought about by task-dependent changes in the balance of excitatory and
      inhibitory neural activity.

PMID- 21093551
TI  - Fluoride induces apoptosis and alters collagen I expression in rat osteoblasts.
AB  - In this study we investigated apoptosis and expression of the collagen I gene in
      newborn rat osteoblasts (OB) by the administration of varying concentrations of
      fluoride (F). Sodium fluoride (NaF) at concentrations of 0, 0.5, 5, 10, and
      20mg/L was administered to cultured OB. The percentage of G(1)/G(0) (Gap 1/Gap
      0), S (synthesis), G(2)/M (Gap 2/M, mitosis), and apoptosis rates in OB were
      analyzed with a Fluorescence-activated Cell Sorter (FACS) by propidium iodine
      (PI) staining after F treatment of 72 h. Effects of F treatment on COL1A1 and
      COL1A2 mRNA and collagen I protein levels were determined using quantitative real
      time RT-PCR (qRT-PCR) and immunofluorescence, respectively. This study
      demonstrates that there is a pronounced negative effect of long term NaF
      treatment on OB survival. These negative effects include an inhibition of the
      transformation from S phase into G(2)/M phase, increased apoptosis, and decreased
      COL1A1 mRNA, down-regulating the synthesis of COL I protein. The results suggest
      that COL I protein degradation in OB from F toxicity is due to a depletion of
      COL1A1 mRNA and not COL1A2.

PMID- 21093552
TI  - Amphetamine modulates cellular recruitment and airway reactivity in a rat model
      of allergic lung inflammation.
AB  - Asthma is characterized by pulmonary cellular infiltration, vascular exudation
      and airway hyperresponsiveness. Several drugs that modify central nervous system
      (CNS) activity can modulate the course of asthma. Amphetamine (AMPH) is a highly
      abused drug that presents potent stimulating effects on the CNS and has been
      shown to induce behavioral, biochemical and immunological effects. The purpose of
      this study was to investigate the effects of AMPH on pulmonary cellular influx,
      vascular permeability and airway reactivity. AMPH effects on adhesion molecule
      expression, IL-10 and IL-4 release and mast cell degranulation were also studied.
      Male Wistar rats were sensitized with ovalbumin (OVA) plus alum via subcutaneous
      injection. One week later, the rats received another injection of OVA-alum
      (booster). Two weeks after this booster, the rats were subjected to AMPH
      treatment 12 h prior to the OVA airway challenge. In rats treated with AMPH, the
      OVA challenge reduced cell recruitment into the lung, the vascular permeability
      and the cellular expression of ICAM-1 and Mac-1. Additionally, elevated levels of
      IL-10 and IL-4 were found in samples of lung explants from allergic rats. AMPH
      treatment, in comparison, increased IL-10 levels but reduced those of IL-4 in the
      lung explants. Moreover, the tracheal responsiveness to methacholine (MCh), as
      well as to an in vitro OVA challenge, was reduced by AMPH treatment, and levels
      of PCA titers were not modified by the drug. Our findings suggest that single
      AMPH treatment down-regulates several parameters of lung inflammation, such as
      cellular migration, vascular permeability and tracheal responsiveness. These
      results also indicate that AMPH actions on allergic lung inflammation include
      endothelium-leukocyte interaction mechanisms, cytokine release and mast cell
      degranulation.

PMID- 21093553
TI  - Investigation of triacetin effect on indomethacin release from poly(methyl
      methacrylate) microspheres: evaluation of interactions using FT-IR and NMR
      spectroscopies.
AB  - The purpose of this study was to form indomethacin (IND)-loaded poly(methyl
      methacrylate) (PMMA) microspheres having an extended drug release profile over a
      period of 24h. Microspheres were prepared by solvent evaporation method using
      sucrose stearate as a droplet stabilizer. When PMMA was used alone for the
      preparation of microspheres, only 44% of IND could be released at the end of 8h.
      Triacetin was added to PMMA, as a minor phase, and the obtained microspheres
      showed a high yield process with recovery of 89.82% and incorporation efficiency
      of 102.3%. A desired release profile lasting 24h was achieved. Differential
      scanning calorimetry (DSC) analysis showed that IND was found to be in an
      amorphous state in the microspheres. Fourier transform infrared (FT-IR) and
      nuclear magnetic resonance ((1)H NMR) spectra suggested that there might be a
      hydrogen bond present between the IND hydroxyl group and PMMA. No interaction
      between triacetin and IND or PMMA as the formation of secondary bonds was
      observed. The release enhancement of IND from microspheres was attributed to the
      physical plasticization effect of triacetin on PMMA and, to some extent, the
      amorphous state of the drug.

PMID- 21093554
TI  - Supramolecular interactions between losartan and hydroxypropyl-beta-CD: ESI mass
      spectrometry, NMR techniques, phase solubility, isothermal titration calorimetry
      and anti-hypertensive studies.
AB  - In this work, low soluble supramolecular complex between the losartan potassium
      (Los) and hydroxypropil-beta-cyclodextrin (HPbetaCD) were characterized
      throughout phase-solubility, NMR techniques ((1)H and 2D-ROESY) and isothermal
      titration calorimetry (ITC) in order to attain physical-chemical knowledge of the
      system. In addition, the hypertensive effect of composition Los/HPbetaCD was
      evaluated aiming to obtain a more efficient oral pharmaceutical composition. ESI
      mass spectrometry and ITC blank experiment demonstrate the presence of Los
      clusters at 30 mM pure solution. Phase-solubility experiments showed a "Bs" type
      system, due to the formation of a less soluble complex than pure Los. NMR
      demonstrated the short distance interactions between the Los and the
      cyclodextrin, where several possibilities of interactions were observed. ITC data
      suggest an average 1:1 stoichiometry of Los and the cyclodextrin. The complex
      demonstrated efficiency in hypertension control, presenting antagonist action on
      the pressure effect of angiotensin II within 30 h, as compared to Los alone, 6h,
      indicating that inclusion of Los in HPbetaCD enhanced the extent and duration of
      its antagonistic action. In this work, a model of interaction between Los and
      HPbetaCD was proposed based on dissociation of self-assembled Los followed by
      complexation with HPbetaCD.

PMID- 21093555
TI  - A novel, biodegradable and reversible polyelectrolyte platform for topical
      colonic delivery of pentosan polysulphate.
AB  - The goal of the present work was to develop a swellable hydrogel colonic delivery
      system, which would maximise the availability of the therapeutic agent at a site
      of inflammation, especially where the water is scarce. A novel method was
      developed to manufacture a biodegradable and reversible polyelectrolyte complex
      (PEC) containing chitosan and poly acrylic-acid (PAA). The PEC was analysed using
      FTIR and DSC, which confirmed the formation of non-permanent swollen gel-network
      at an alkaline pH. Pentosan polysulphate (PPS) was incorporated in a PEC and an
      activated partial thromboplastin time assay was developed to measure the release
      of PPS from PEC. In vitro studies suggested that the release of PPS was dependent
      on the initial drug loading and the composition of the PEC. The gel strength of
      the swollen network, determined using a texture analyser, was dependent on
      polymer composition and the amount of PPS incorporated. Bacterial enzymes were
      collected from the rat caecum and colon for the digestion studies and
      characterised for glucosidase activity, glucuronidase activity and protein
      content. The digestion of the reversible polyelectrolyte complexes was measured
      using a dinitro salicylic acid assay and an increased release of drug was also
      confirmed in the presence of bacterial enzymes.

PMID- 21093556
TI  - Effects of organic solvents on drug incorporation into polymeric carriers and
      morphological analyses of drug-incorporated polymeric micelles.
AB  - We incorporated an anticancer agent, camptothecin (CPT), into polymeric micelle
      carriers by using two different solvents (TFE and chloroform) in the solvent
      evaporation drug incorporation process. We observed significant differences in
      the drug-incorporation behaviors, in the morphologies of the incorporated drug
      and the polymeric micelles, and in the pharmacokinetic behaviors between the two
      solvents' cases. In particular, the CPT-incorporated polymeric micelles prepared
      with TFE as the incorporation solvent exhibited more stable circulation in blood
      than those prepared with chloroform. This contrast indicates a novel
      technological perspective regarding the drug incorporation into polymeric micelle
      carriers. Morphological analyses of the inner core have revealed the presence of
      the directed alignment of the CPT molecules and CPT crystals in the micelle inner
      core. This is the first report of the morphologies of the drug incorporated into
      the polymeric micelle inner cores. We believe these analyses are very important
      for further pharmaceutical developments of polymeric micelle drug-carrier
      systems.

PMID- 21093557
TI  - Cell line-dependent internalization pathways determine DNA transfection
      efficiency of decaarginine-PEG-lipid.
AB  - Previously, we have reported that decaarginine-conjugated PEG-lipids (R10B)
      efficiently delivered plasmid DNA (pDNA) into human cervical carcinoma HeLa cells
      via macropinocytosis; however, the mechanism of cellular uptake by R10B was not
      evaluated in other cell lines. In this study, we investigated the internalization
      mechanism by R10B/pDNA complex (R10B-lipoplex) in human prostate tumor PC-3 and
      human nasopharyngeal tumor KB cells, and compared with that in HeLa cells.
      Although it was necessary for R10B-lipoplex to associate with heparan sulfate
      (HS) on the cell surface in all cell lines, the R10B-lipoplex was internalized
      primarily through clathrin-mediated endocytosis in PC-3 and KB cells, and
      macropinosytosis in HeLa cells. In HeLa cells, treatment with the R10B-lipoplex
      induced the formation of lamellipodia for macropinocytosis, but did not in KB and
      PC-3 cells. Furthermore, the highest transfection efficiency by R10B-lipoplex was
      observed in HeLa cells. These findings indicated that the R10B-lipoplex induced
      the formation of lamellipodia in HeLa cells after binding to HS on the cells and
      was then internalized by macropinocytosis, which could induce high gene
      expression because of escaping degradation in lysosomes. Cell physiology might be
      a critical factor in cellular internalization and efficient transfection by cell
      penetration peptide.

PMID- 21093558
TI  - Formation of bicalutamide nanodispersion for dissolution rate enhancement.
AB  - Bicalutamide was loaded on hydrophilic excipients to form nanodispersions via a
      combination of anti-solvent precipitation and spray drying method. The particle
      size, BET surface area, contact angles and dissolution rate of the
      nanodispersions were analyzed. The results indicated that lactose was a suitable
      matrix to prevent the bicalutamide particles growth and aggregation. The lactose
      loaded particles had a mean size of 330 nm within a narrow distribution. X-ray
      diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform
      infrared (FT-IR) characterization indicated the nanodispersion exhibited
      unchanged crystalline and chemical structure. Dissolution rate of bicalutamide
      nanodispersion was significantly faster than that of commercial products. It
      increased to 94% in 10 min while both commercial formulas Casodex and
      bicalutamide tablets dissolved 60% and 38% respectively at the same period. It
      was proposed that the enhanced dissolution rate of bicalutamide nanodispersion
      contribute to high surface area and well-wetted state of drug particles.

PMID- 21093559
TI  - Preparation of a chemically stable quercetin formulation using nanosuspension
      technology.
AB  - In the present study the evaporative precipitation into aqueous solution (EPAS)
      process and the high homogenization press (HPH) process were compared to evaluate
      their feasibility to form a chemically stable quercetin nanosuspension. The
      particle size and Zeta potential of the EPAS nanosuspension were similar to those
      of the HPH nanosuspension. Differences in results of differential scanning
      calorimetery and X-ray measures were observed between the two processes. The
      crystalline-to-amorphous phase transition was shown in the profile of EPAS dried
      powder. On the contrary the initial crystalline state of drug was maintained
      throughout the HPH process. Dissolution test results indicated that the EPAS
      process showed a higher improvement in the drug solubility and dissolution rate
      than the HPH process. At last the high performance liquid chromatography (HPLC)
      analysis proved the superiority of both nanosuspensions over QCT solution
      formulation for the chemical and photo-stability. As a result, it can be
      concluded that the EPAS and HPH techniques were feasible to prepare a chemically
      stable QCT nanosuspension with significantly enhanced dissolution rate.

PMID- 21093560
TI  - Spray-freeze-drying production of thermally sensitive polymeric nanoparticle
      aggregates for inhaled drug delivery: effect of freeze-drying adjuvants.
AB  - Inhalable dry-powder aggregates of drug-loaded thermally sensitive
      poly(caprolactone) (PCL) nanoparticles are produced using spray-freeze-drying
      (SFD) as the low melting point of PCL prohibits the use of high-temperature spray
      drying. The effects of freeze-drying adjuvant formulation on the particle
      morphology, aerodynamic diameter, aqueous re-dispersibility, flowability, and
      production yield are examined using mannitol and poly(vinyl alcohol) (PVA) as the
      adjuvants. The primary role of the adjuvant is to prevent irreversible
      nanoparticle coalescences during freeze-drying, thereby the nanoparticle
      aggregates can readily re-disperse into primary nanoparticles in an aqueous
      environment hence retaining their therapeutic functions. The nanoparticle
      aggregates produced using either adjuvant exhibit large, porous, and spherical
      morphologies suitable for dry-powder-inhaler delivery. The nanoparticle
      aggregates exhibit good flowability and effective aerosolization off the inhaler.
      The adjuvant selection governs the resultant nanoparticle-adjuvant structures,
      where PCL nanoparticles are physically dispersed in porous mannitol matrix,
      whereas PVA are coated onto the nanoparticle surface. Importantly, nanoparticle
      aggregates produced by SFD exhibit significantly higher aqueous re-dispersibility
      than those produced by spray-drying, which signifies the suitability of SFD as
      the method to produce solid-dosage-form of thermally sensitive nanoparticles.
      Overall, using PVA as adjuvant leads to more stable morphology, superior aqueous
      re-dispersibility, and higher production yield compared to the mannitol
      formulation.

PMID- 21093561
TI  - Zn-Al-NO(3)-layered double hydroxides with intercalated diclofenac for ocular
      delivery.
AB  - This study was aimed to evaluate the potential use of a drug delivery system,
      drug-layered double hydroxide (LDH) nanocomposites for ocular delivery.
      Diclofenac was successfully intercalated into Zn-Al-NO(3)-LDH by coprecipitation
      method. The nanocomposites were characterized by particle size, elemental
      chemical analysis, thermogravimetric analysis, etc. A tilt bilayer of diclofenac
      molecules formed in the interlayer with the gallery height of 1.868 nm. In vivo
      precorneal retention studies were conducted with diclofenac sodium (DS) saline,
      diclofenac-LDH nanocomposite dispersion, 2% polyvinylpyrrolidone (PVP) K30
      diclofenac-LDH nanohybrid dispersion and 10% PVP K30-diclofenac-LDH nanohybrid
      dispersion, separately. Compared with DS saline, all the dispersions have
      extended the detectable time of DS from 3h to 6h; C(max) and AUC(0-t) of
      diclofenac-LDH nanocomposite dispersion showed 3.1-fold and 4.0-fold increase,
      respectively; C(max) and AUC(0-t) of 2% PVP K30-LDH nanohybrid dispersion were
      about 5.3-fold and 6.0-fold enhancement, respectively. Results of the Draize test
      showed that no eye irritation was demonstrated in rabbits after single and
      repeated administration. These results suggest that this novel ocular drug
      delivery system appears to offer promise as a means to improving the
      bioavailability of drugs after ophthalmic applications.

PMID- 21093562
TI  - Electrohydrodynamic preparation of polymeric drug-carrier particles: mapping of
      the process.
AB  - Submicrometre size spheres prepared from biocompatible polymers are becoming
      increasingly popular in drug and gene delivery. This paper describes the
      preparation of polymeric spheres with a mean diameter of 0.4 MUm with a
      polydispersivity index of 8%, using coaxial electrohydrodynamic atomization
      (CEHDA) microbubbling. An 18 wt.% solution of polymethylsilsesquioxane, a
      hydrophobic biocompatible polymer, was subjected to CEHDA microbubbling by
      passing air through the inner needle and polymer solution through the outer
      needle of a twin needle co-axial device, under the influence of an electric
      field. A parametric plot of the flow rate of air and the flow rate of polymer
      solution was constructed and used for systematic process control to reduce the
      diameter of the microspheres from micrometre size to submicrometre size. CEHDA is
      an excellent method for obtaining polymer microspheres. By studying the process
      in detail and mapping it, we can now demonstrate it can also be used to prepare
      submicrometre sized particles with the ability to control size and
      polydispersivity.

PMID- 21093563
TI  - Development and in vitro characterization of paclitaxel and docetaxel loaded into
      hydrophobically derivatized hyperbranched polyglycerols.
AB  - In this study we report the development and in vitro characterization of
      paclitaxel (PTX) and docetaxel (DTX) loaded into hydrophobically derivatized
      hyperbranched polyglycerols (HPGs). Several HPGs derivatized with hydrophobic
      groups (C(8/10) alkyl chains) (HPG-C(8/10)-OH) and/or methoxy polyethylene glycol
      (MePEG) chains (HPG-C(8/10)-MePEG) were synthesized. PTX or DTX were loaded into
      these polymers by a solvent evaporation method and the resulting nanoparticle
      formulations were characterized in terms of size, drug loading, stability,
      release profiles, cytotoxicity, and cellular uptake. PTX and DTX were found to be
      chemically unstable in unpurified HPGs and large fractions (~80%) of the drugs
      were degraded during the preparation of the formulations. However, both PTX and
      DTX were found to be chemically stable in purified HPGs. HPGs possessed
      hydrodynamic radii of less than 10nm and incorporation of PTX or DTX did not
      affect their size. The release profiles for both PTX and DTX from HPG-C(8/10)
      MePEG nanoparticles were characterized by a continuous controlled release with
      little or no burst phase of release. In vitro cytotoxicity evaluations of PTX and
      DTX formulations demonstrated a concentration-dependent inhibition of
      proliferation in KU7 cell line. Cellular uptake studies of rhodamine-labeled HPG
      (HPG-C(8/10)-MePEG(13)-TMRCA) showed that these nanoparticles were rapidly taken
      up into cells, and reside in the cytoplasm without entering the nuclear
      compartment and were highly biocompatible with the KU7 cells.

PMID- 21093564
TI  - Amelioration of dementia induced by Abeta 22-35 through rectal delivery of
      undecapeptide-hEGF to mouse brain.
AB  - A group of growth factors have been shown to play important roles in amelioration
      of the malfunction of the neurodegenerative diseases. However, the proteins or
      polypeptides passing across the blood-brain barrier (BBB) to access the brain
      parenchyma are relatively few so that it hinders the therapies in clinic. Here a
      genetically reconstructed fusion peptide of human epidermal growth factor (hEGF)
      with an undecapeptide YGRKKRRQRRR (P11) was used to investigate the permeability
      between the cell membrane and the BBB via rectal administration. The efficiency
      to rescue the Abeta 22-35-induced dementia in mice was assessed after
      administration of P11-hEGF per rectal. Our results showed that P11-hEGF permeates
      across not only the 3T3 cell membrane in vitro, but also the endothelia of
      vessels after intravenous injection (IV), and the mucosa of the rectum after per
      rectal administration. Further results showed that the circulating P11-hEGF
      allowed penetrating through the blood-brain barrier and then getting into the
      brain manifesting biological responses. In the animal experiments, treatment with
      P11-hEGF not only ameliorated the dementia induced by Abeta 22-35 but also
      rescued the dementia of the aged mice, no matter how it was administrated (IV or
      per rectal). These results suggest that the rectal non-invasive delivery of the
      P11 polypeptide-conjugated growth factor is an efficient way for BBB
      transduction, thus raises the hope of real therapeutic progress against
      neurodegenerative diseases.

PMID- 21093565
TI  - Retinyl acetate-loaded nanoparticles: dermal penetration and release of the
      retinyl acetate.
AB  - Retinyl acetate (RA) loaded polymeric nanoparticle (NP) carriers were prepared
      using two different single polymers, ethyl cellulose (EC) and poly (ethylene
      glycol)-4-methoxycinnamoylphthaloylchitosan (PCPLC). The stability of RA to
      aqueous solution and UVA light was significantly improved when encapsulated with
      PCPLC, whilst EC encapsulation gave some improved stability in water but showed
      no improved photostability. Ex vivo application of free RA and the RA-loaded
      PCPLC NPs onto the surface of the freshly excised skin from a baby mouse
      indicated a significantly slower skin absorption rate for the encapsulated RA.
      However, 100% retention of the encapsulated RA in the skin tissue was observed
      after 24h. Confocal fluorescent analysis of the skin pieces applied with the RA
      loaded PCPLC NPs indicated likely entry and accumulation of the PCPLC NPs and RA
      at the hair follicles. Release of RA from the PCPLC NP carriers was confirmed
      through the detection of an increasingly higher RA/PCPLC fluorescent signal ratio
      deeper into the dermis and away from the hair follicles.

PMID- 21093566
TI  - Dry elixir formulations of dexibuprofen for controlled release and enhanced oral
      bioavailability.
AB  - The objective of this study was to achieve an optimal formulation of dexibuprofen
      dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To
      control the release rate of dexibuprofen, Eudragit((r)) RS was employed on the
      surface of DDE resulting in coated dexibuprofen dry elixir (CDDE).
      Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and
      contents of dexibuprofen and ethanol were characterized. Pharmacokinetic
      parameters of dexibuprofen were evaluated in the rats after oral administration.
      The DDE and CDDE were spherical particles of 12 and 19 MUm, respectively. The
      dexibuprofen and ethanol contents in the DDE were dependent on the amount of
      dextrin and maintained for 90 days. The dissolution rate and bioavailability of
      dexibuprofen loaded in dry elixir were increased compared with those of
      dexibuprofen powder. Moreover, coating DDE with Eudragit((r)) RS retarded the
      dissolution rate of dexibuprofen from DDE without reducing the bioavailability.
      Our results suggest that CDDE may be potential oral dosage forms to control the
      release and to improve the bioavailability of poorly water-soluble dexibuprofen.

PMID- 21093568
TI  - In vitro and in vivo acute antihyperglycemic effects of five selected indigenous
      plants from Jordan used in traditional medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Achillea santolina L., Pistacia atlantica Desf,
      Rheum ribes L., Sarcopoterium spinosum (L.) Spach and Teucrium polium L. have
      traditionally been used as herbal antidiabetic medicines. However their alleged
      benefits and mechanisms remain elusive. AIM OF THE STUDY: This study aimed to
      evaluate the effect of water extracts of these plants in in vitro and in vivo
      experiments. MATERIALS AND METHODS: In vitro enzymatic starch digestion with
      aqueous extracts from plants at concentrations of 1, 5, 10, 12.5, 25, 50 and 100
      mg/ml was assayed using alpha-amylase and alpha-amyloglucosidase. Acarbose was
      used as control and glucose liberation was determined by glucose oxidase method.
      Oral starch tolerance test (OSTT) and oral glucose tolerance test (OGTT) were
      determined for the plant extracts at concentrations 125, 250 and 500 mg/kg b.wt.
      on Sprague-Dawley rats. Blood glucose levels in rats treated with plant extracts
      and drugs (acarbose or metformin and glipizide) were measured at -30, 0, 45, 90
      and 135 min. RESULTS: Compared to acarbose (IC(50)=1.2 MUg/ml), water extracts of
      Pistacia atlantica, Rheum ribes and Sarcopoterium spinosum exerted significant
      dose dependent dual inhibition of alpha-amylase and alpha-glucosidase in in vitro
      enzymatic starch digestion bioassay, with IC(50)s; 46.98, 58.9 and 49.9 mg/ml,
      respectively. Comparable in vivo results were obtained for starch-fed rats,
      exhibiting significant acute postprandial antihyperglycemic efficacies. While
      Achillea santolina and Teucrium polium extracts lacked any favourable in vitro
      anti-alpha-amylase and anti-alpha-glucosidase effect, other modes of action can
      possibly explain their substantial acute antihyperglycemic activities in starch
      treated rats. Except for Pistacia atlantica extracts, none of the investigated
      extracts qualified for improving the glucose intolerance in fasted rats on
      glucose loading. CONCLUSIONS: Pistacia atlantica, Rheum ribes and Sarcopoterium
      spinosum can be considered as potential candidates for amelioration/management of
      type 2 diabetes.

PMID- 21093569
TI  - The use of plants in the medical system of the Fulni-o people (NE Brazil): a
      perspective on age and gender.
AB  - OBJECTIVES: The loss of traditional knowledge and practices is currently a widely
      discussed topic in the academic literature. From this perspective, this study was
      constructed with the main goals of evaluating Fulni-o Indians' knowledge about
      medicinal plants and how this knowledge is influenced by age and gender.
      Additionally, this study seeks to identify the sites where these resources are
      collected. METHODS: In order to meet our intended objectives, we performed a
      stratified sampling of the population; 344 indigenous persons were interviewed in
      an open-ended format. RESULTS: Although a total of 245 ethnospecies were
      mentioned overall, more than 50% of these plants were known by no more than three
      indigenous persons, which could indicate that such knowledge was not widely
      shared. Evaluating the influence of age, we identified a strong tendency for
      older persons to know more about medicinal plants than those in younger age
      groups. However, a critical analysis of the informants' age groups demonstrated
      that significant differences were present only among some of these groups. The
      oldest group of indigenous people (>75 years) had inferior knowledge about
      medicinal plants and the diversity of the ethnospecies they cited was similar to
      the younger age groups. In relation to gender, men cited a total of 196 different
      ethnospecies and 82 of these species were exclusive to their group. Also, men
      have their specific ethnospecies not mentioned by women. Women cited 165 species
      and 51 were exclusive to their group. This indicates that although women
      generally held less knowledge of ethnospecies than the men, they did discuss a
      set of ethnospecies that were not mentioned by men. However, men on average cited
      more ethnospecies than women and this data support the existence of differences
      between the sexes. CONCLUSIONS: Despite the lack of substantial variation in the
      number of ethnospecies cited by men and women on the individual level, the
      differences between the sexes as groups were significant. Diverse collection
      sources were used to attend to the therapeutic needs of the Fulni-o Indians.
      Among the most important collection sites, anthropogenic areas were the primary
      collection sites for women, followed by the Ouricuri Forest, which was the main
      collection site for male indigenous persons.

PMID- 21093567
TI  - Formation and maturation of the calyx of Held.
AB  - Sound localization requires precise and specialized neural circuitry. A prominent
      and well-studied specialization is found in the mammalian auditory brainstem.
      Globular bushy cells of the ventral cochlear nucleus (VCN) project
      contralaterally to neurons of the medial nucleus of the trapezoid body (MNTB),
      where their large axons terminate on cell bodies of MNTB principal neurons,
      forming the calyces of Held. The VCN-MNTB pathway is necessary for the accurate
      computation of interaural intensity and time differences; MNTB neurons provide
      inhibitory input to the lateral superior olive, which compares levels of
      excitation from the ipsilateral ear to levels of tonotopically matched inhibition
      from the contralateral ear, and to the medial superior olive, where precise
      inhibition from MNTB neurons tunes the delays of binaural excitation. Here we
      review the morphological and physiological aspects of the development of the VCN
      MNTB pathway and its calyceal termination, along with potential mechanisms that
      give rise to its precision. During embryonic development, VCN axons grow towards
      the midline, cross the midline into the region of the presumptive MNTB and then
      form collateral branches that will terminate in calyces of Held. In rodents,
      immature calyces of Held appear in MNTB during the first few days of postnatal
      life. These calyces mature morphologically and physiologically over the next
      three postnatal weeks, enabling fast, high fidelity transmission in the VCN-MNTB
      pathway.

PMID- 21093570
TI  - Potential antimalarials from Nigerian plants: a review.
AB  - Malaria, caused by parasites of the genus Plasmodium, is one of the leading
      infectious diseases in many tropical regions, including Nigeria, a West African
      country where transmission occurs all year round. Many of the inhabitants use
      plants as remedies against fever and other symptoms of acute malaria, as reported
      herein. Some of these plants have their antimalarial efficacies scientifically
      demonstrated and the active compounds isolated with their probable mechanisms of
      action studied. Medicinal plants are used to treat diseases also where the
      biodiversity of plants occur in parallel with endemic transmission of malaria.
      This review focuses on medicinal plants which are used to treat malaria in
      Nigeria, and on antimalarial testing of extracts and purified compounds from
      plants. Some show intense activity against malaria parasites in vitro and in
      experimentally infected mice. The search for new drugs based on plants is
      important due to the emergence and widespread of chloroquine-resistant and
      multiple drug-resistant malaria parasites, which require the development of new
      antimalarials. An acquaintance with antimalarial plants may be a springboard for
      new phytotherapies that could be affordable to treat malaria, especially among
      the less privileged native people living in endemic areas of the tropics, mostly
      at risk of this devastating disease.

PMID- 21093571
TI  - In vitro modulatory effects of Andrographis paniculata, Centella asiatica and
      Orthosiphon stamineus on cytochrome P450 2C19 (CYP2C19).
AB  - ETHNO PHARMACOLOGICAL RELEVANCE: Andrographis paniculata (AP), Centella asiatica
      (CA) and Orthosiphon stamineus (OS) are three popular herbs traditionally used
      worldwide. AP is known for the treatment of infections and diabetes and CA is
      good for wound healing and healthy skin while OS is usually consumed as tea to
      treat kidney and urinary disorders. Interaction of these herbs with human
      cytochrome P450 2C19 (CYP2C19), a major hepatic CYP isoform involved in
      metabolism of many clinical drugs has not been investigated to date. AIM OF THE
      STUDY: In this study, the modulatory effects of various extracts and major active
      constituents of AP, CA and OS on CYP2C19 activities were evaluated. MATERIALS AND
      METHODS: S-mephenytoin, the CYP2C19 substrate probe, was incubated in the
      presence or absence of AP, CA and OS components. The changes in the rate of
      metabolite (hydroxymephenytoin) formation were subsequently determined by a high
      performance liquid chromatography (HPLC)-based enzyme assay to characterize the
      modulatory effects. RESULTS: Among the herbal extracts studied, AP ethanol
      extract and CA dichloromethane extract exhibited mixed type inhibition towards
      CYP2C19 with K(i) values of 67.1 and 16.4 MUg/ml respectively; CA ethanol extract
      and OS petroleum ether extract competitively inhibited CYP2C19 activity
      (K(i)=39.6 and 41.5 MUg/ml respectively). Eupatorin (a major active constituent
      of OS) was found to significantly inhibit CYP2C19 by mixed type inhibition
      (K(i)=7.1 MUg/ml or 20.6 MUM). CONCLUSIONS: It was observed that AP, CA and OS
      inhibited CYP2C19 activity with varying potency. While weak inhibitory effect was
      observed with AP, moderate to strong inhibition was observed with CA
      dichloromethane extract and eupatorin, the major OS constituent. Therefore care
      should be taken when these CA and OS components are co-administered with CYP2C19
      substrates (such as omeprazole, proguanil, barbiturates, citalopram, and
      diazepam).

PMID- 21093572
TI  - The antidiarrheal and spasmolytic activities of Phyllanthus emblica are mediated
      through dual blockade of muscarinic receptors and Ca2+ channels.
AB  - AIM OF THE STUDY: This study was aimed at providing the possible mechanisms for
      the medicinal use of Phyllanthus emblica in diarrhea. MATERIALS AND METHODS: The
      in vivo studies were conducted in mice, while isolated rabbit jejunum and guinea
      pig ileum were used for the in vitro experiments. RESULTS: The crude extract of
      Phyllanthus emblica (Pe.Cr), which tested positive for alkaloids, tannins,
      terpenes, flavonoids, sterols and coumarins, caused inhibition of castor oil
      induced diarrhea and intestinal fluid accumulation in mice at 500-700 mg/kg. In
      isolated rabbit jejunum, Pe.Cr relaxed carbachol (CCh) and K(+) (80 mM)-induced
      contractions, in a pattern similar to that of dicyclomine. The preincubation of
      guinea pig-ileum with Pe.Cr (0.3 mg/mL), caused a rightward parallel shift in the
      concentration-response curves (CRCs) of acetylcholine without suppression of the
      maximum response. While at the next higher concentration (1 mg/mL), it produced a
      non-parallel rightward shift with suppression of the maximum response, similar to
      that of dicyclomine, suggesting anticholinergic and Ca(2+) channel blocking (CCB)
      like antispasmodic effect. The CCB-like activity was further confirmed when
      pretreatment of the tissue with Pe.Cr, shifted the CRCs of Ca(2+) to the right
      with suppression of the maximum response, similar to nifedipine or dicyclomine.
      The activity-directed fractions of Pe.Cr showed a combination of Ca(2+)
      antagonist and anticholinergic like components in all fractions but with varying
      potency. CONCLUSION: These results indicate that the Phyllanthus emblica fruit
      extract possesses antidiarrheal and spasmolytic activities, mediated possibly
      through dual blockade of muscarinic receptors and Ca(2+) channels, thus
      explaining its medicinal use in diarrhea.

PMID- 21093573
TI  - Induction of intercellular adhesion molecule-1 by water-soluble components of
      Hericium erinaceum in human monocytes.
AB  - AIM OF THE STUDY: Hericium erinaceum is a medicinal mushroom that has been
      traditionally used in Asian countries for the treatment of cancers and infectious
      diseases. Although the immunomodulating activity of H. erinaceum is considered to
      be responsible for its medicinal activity, its action mechanisms are poorly
      understood. In the present study, we investigated the capability of water
      extracted H. erinaceum (WEHE) to induce the expression of intercellular adhesion
      molecule-1 (ICAM-1), which regulates the migration of immune cells. MATERIALS AND
      METHODS: THP-1, a human monocytic cell-line, or human peripheral blood
      mononuclear cells (PBMC) were stimulated with WEHE (0-30 MUg/mL) and subsequently
      analyzed using flow cytometry to examine the surface expression of ICAM-1
      protein. Steady-state levels of ICAM-1 mRNA were estimated using real-time
      reverse transcription-polymerase chain reaction analysis. Electrophoretic
      mobility shift assay was conducted to examine transcription factors involved in
      ICAM-1 transcription. RESULTS: WEHE induced ICAM-1 expression at both protein and
      mRNA levels in THP-1 cells in a dose- and time-dependent fashion. A similar
      pattern of ICAM-1 induction was also observed in CD14(+) monocytes in human PBMC
      that were stimulated with WEHE. The ICAM-1 expression on THP-1 cells stimulated
      with WEHE was suppressed by specific inhibitors for extracellular signal
      regulated kinases (ERK) and reactive oxygen species (ROS). Additionally, exposure
      of THP-1 cells to WEHE increased the DNA binding activities of NF-kappaB, AP-1,
      SP-1 and STAT-1 transcription factors, all of which are known to be required for
      ICAM-1 gene expression. CONCLUSIONS: These results suggest that WEHE induces ICAM
      1 expression in human monocytes through ERK- and ROS-dependent signaling
      pathways, resulting in the subsequent activations of NF-kappaB, AP-1, SP-1, and
      STAT-1 transcription factors.

PMID- 21093574
TI  - Trigger factor of Streptococcus suis is involved in stress tolerance and
      virulence.
AB  - Streptococcus suis serotype 2 is an important zoonotic pathogen that causes
      serious diseases such as meningitis, septicemia, endocarditis, arthritis and
      septic shock in pigs and humans. Little is known about the regulation of
      virulence gene expression in S. suis serotype 2. In this study, we cloned and
      deleted the entire tig gene from the chromosome of S. suis serotype 2 SC21
      strain, and constructed a mutant strain (Deltatig) and a complementation strain
      (CDeltatig). The results demonstrated that the tig gene, encoding trigger factor
      from S. suis serotype 2 SC21, affects the stress tolerance and the expression of
      a few virulence genes of S. suis serotype 2. Deletion of the tig gene of S. suis
      serotype 2 resulted in mutant strain, DeltaTig, which exhibited a significant
      decrease in adherence to cell line HEp-2, and lacked hemolytic activity. Tig
      deficiency diminishes stresses tolerance of S. suis serotype 2 such as survive
      thermal, oxidative and acid stresses. Quantification of expression levels of
      known S. suis serotype 2 SC21 virulence genes by real-time polymerase chain
      reaction in vitro revealed that trigger factor influences the expression of epf,
      cps, adh, rpob, fbps, hyl, sly, mrp and hrcA virulence-associated genes. DeltaTig
      was shown to be attenuated in a LD50 assay and bacteriology, indicating that
      trigger factor plays an important part in the pathogenesis and stress tolerance
      of. S. suis serotype 2 infection. Mutant DeltaTig was 100% defective in virulence
      in CD1 mice at up to 107 CFU, and provided 100% protection when challenged with
      107 CFU of the SC21 strain.

PMID- 21093575
TI  - XTT assay for evaluating the effect of alcohols, hydrogen peroxide and
      benzalkonium chloride on biofilm formation of Staphylococcus epidermidis.
AB  - To analyze the degree of biofilm formation on three ica-positives Staphylococcus
      epidermidis as a function of biocides, the medium was supplemented with
      increasing concentrations of isopropanol, ethanol, and methanol at 0, 1, 4, 6, 8,
      10, 12 and 14% (v/v), hydrogen peroxide (0, 0.125, 0.25, 0.5, 1, 2, 3, 4 and 5%
      v/v) and benzalkonium chloride (0, 0.125, 0.25, 0.5, 1, 2, 3, 4 and 6 MUg ml-1).
      In biocide-free biofilms, the results showed that two strains (S. epidermidis
      CIP106510 and E24) were strongly biofilm positive displaying a high oxidative
      activity (1.254 and 0.855, respectively) in comparison with the non-adherent one
      (S22). In addition biofilm formation was induced with 1% alcohol (isopropanol and
      ethanol) supplementation. The three studied strains cultured in TSB supplemented
      with 2% methanol displayed a strong oxidative activity (P=0.008). Moreover wells
      with 0.125% hydrogen peroxide enhanced increasing oxidative activity of S.
      epidermidis CIP106510 and S22. A significant induction of biofilm was noted after
      treatment with 1 MUg ml-1 of benzalkonium chloride. This study suggests that some
      biocides currently used in hospitals are ineffective against nosocomial pathogens
      growing in biofilms when used at weak concentration and fail to control this
      reservoir for hospital-acquired infection.

PMID- 21093576
TI  - Anticancer properties of 10-hydroxycamptothecin in a murine melanoma pulmonary
      metastasis model in vitro and in vivo.
AB  - Lung cancer, including lung metastatic cancer, remains one of the most difficult
      types of cancer to treat. Therefore, the search for new agents for its treatment
      is very important. 10-Hydroxycamptothecin (HCPT) was proved to have ideal
      anticancer activity in curing series cancer cells. In this study, the anticancer
      effect of HCPT on melanoma lung metastasis cancer was investigated by several
      administration routes, and whether the effect may be attributed to the induction
      of tumor cells apoptosis was determined. MTT assay results showed that HCPT
      exhibited selective cytotoxic activity against B16-F10 cells in a concentration-
      and time-dependent manner. Hoechst 33258 staining and transmission electron
      microscopy showed typical apoptotic morphology such as condensed chromatin,
      irregular nuclei, and apoptotic body formation. Flow cytometry analysis indicated
      a growth on apoptotic cells and a cell-cycle arrest in S phase after treatment
      with HCPT. In vivo melanoma pulmonary metastases were inhibited by treatment with
      HCPT. A more significant inhibition was observed if HCPT was administered by
      aerosol inhalation than that given by i.v. or i.p. administration. Thus, HCPT
      exhibited potential anticancer activity against B16-F10 cells in vitro and in
      vivo. However, the possible mechanisms involved still need to be investigated to
      explain this behavior.

PMID- 21093577
TI  - mRNA expression of alpha and beta isoforms of glucocorticoid receptor in
      peripheral blood mononuclear cells of patients with tuberculosis and its relation
      with components of the immunoendocrine response.
AB  - We have analyzed the expression of glucocorticoid receptor (GR) isoforms by real
      time RT-qPCR in PBMCs from 19 controls (HCo) and 28 TB patients (8 mild; 12
      moderate; 8 severe), HIV(-) and similar sex and age distribution. mRNA
      hGRalpha/beta ratios were found higher in TB patients respect to those in HCo.
      However, when analyzing for disease severity such overall trend was at the
      expense of mild and moderate patients, with severe cases showing a lower mRNA
      hGRalpha/beta ratio with respect to the other patient groups. This suggested some
      degree of resistance to endogenous glucocorticoids in patients with severe TB,
      since hGRalphaalpha dimer mediates the biological functions of GC, with the
      GRbeta isoform acting as an inhibitor of GC activity. Levels of IL-6, IL-18, IFN
      gamma and Cortisol were significantly increased in severe and moderate cases,
      whereas DHEA values were found decreased in them (p<0.05 respect to HCo).
      Analysis on the relationship between plasma levels of these immuno-endocrine
      mediators with the mRNA expression of hGRalpha and hGRbeta showed that IL-6 was
      positively associated with hGRalpha in mild TB patients (p<0.01), whereas a
      negative correlation between IFN-gamma and hGRbeta was observed in severe cases
      (p<0.01). As regard to hormones, DHEA was positively associated with hGRalpha in
      moderate and severe cases (p<0.01). This group also showed a negative correlation
      between hGRalpha and Cortisol/DHEA ratios (p<0.05). Changes in the systemic
      levels of cytokine and adrenal hormones are likely to affect GR expression in a
      differential fashion and according to the amount of pulmonary involvement.

PMID- 21093579
TI  - Effects of stressors and immune activating agents on peripheral and central
      cytokines in mouse strains that differ in stressor responsivity.
AB  - The impact of inflammatory immune activation on behavioral and physiological
      processes varies with antecedent stressor experiences. We assessed whether immune
      activation would differentially influence such outcomes as a function of stressor
      reactivity related to genetic differences. To this end, we assessed the influence
      of a social stressor (exposure to a dominant mouse) in combination with an acute
      immune challenge on behavior and on peripheral and central cytokines in stressor
      reactive BALB/cByJ mice and the less reactive C57BL/6ByJ strain. As C57BL/6ByJ
      and BALB/cByJ mice are highly T helper type-1 (Th1) and Th2 responsive,
      respectively, the stressor effects were assessed in response to different
      challenges, namely the viral analogue poly I:C and the bacterial endotoxin
      lipopolysaccharide (LPS). The stressor enhanced the effects of LPS on sickness
      behaviors and plasma corticosterone particularly in BALB/cByJ mice, whereas the
      effects of poly I:C, which primarily affects Th1 processes, were not augmented by
      the stressor. As well, the stressor increased circulating cytokines in LPS
      treated C57BL/6ByJ mice, whereas the effects of poly I:C were diminished.
      Finally, like circulating cytokines, mRNA expression of pro-inflammatory
      cytokines within the prefrontal cortex and hippocampus varied with the mouse
      strain and with the stressor experience, and with the specific cytokine
      considered. Together, the experiments indicated that the impact of stressors vary
      with the nature of the immune challenge to which animals had been exposed.
      Moreover, given the diversity of the stressor effects on central and peripheral
      processes, it seems likely that the cytokine changes, HPA activity and sickness
      operate through independent mechanisms.

PMID- 21093578
TI  - Alternatively activated myeloid (M2) cells enhance cognitive function in immune
      compromised mice.
AB  - It was recently shown that adaptive immunity plays a key role in cognitive
      function. T cells appear to be major players in learning and memory; thus, mice
      devoid of functional T cells are impaired in performance of cognitive tasks such
      as Morris water maze (MWM), Barnes maze and others. This is a reversible
      phenomenon; injection of immune deficient mice with T cells from wild type
      counterparts improves their cognitive function. Recently we described a critical
      role for T cell-derived IL-4 as having beneficial effects on learning and memory
      through regulation of meningeal myeloid cell phenotype. In the absence of IL-4,
      meningeal myeloid cells acquire a pro-inflammatory skew. Thus, the presence of IL
      4 in the meningeal spaces maintains a delicate balance of pro- and anti
      inflammatory myeloid cell phenotype. Here we show that macrophages alternatively
      activated in vitro (M2 cells) can circumvent the need for 'pro-cognitive' T cells
      when injected intravenously into immune deficient mice. These results show for
      the first time that M2 myeloid cells are new and unexpected players in cognitive
      function, conferring beneficial effects on learning and memory without adaptive
      immune influence. These results might lead to development of new therapeutic
      approaches for cognitive pathologies associated with malfunction of adaptive
      immunity, such as chemo-brain, age-related dementia, HIV-dementia, and others.

PMID- 21093580
TI  - Astrocytes support hippocampal-dependent memory and long-term potentiation via
      interleukin-1 signaling.
AB  - Recent studies indicate that astrocytes play an integral role in neural and
      synaptic functioning. To examine the implications of these findings for
      neurobehavioral plasticity we investigated the involvement of astrocytes in
      memory and long-term potentiation (LTP), using a mouse model of impaired learning
      and synaptic plasticity caused by genetic deletion of the interleukin-1 receptor
      type I (IL-1RI). Neural precursor cells (NPCs), derived from either wild type
      (WT) or IL-1 receptor knockout (IL-1rKO) neonatal mice, were labeled with
      bromodeoxyuridine (BrdU) and transplanted into the hippocampus of either IL-1rKO
      or WT adult host mice. Transplanted NPCs survived and differentiated into
      astrocytes (expressing GFAP and S100beta), but not to neurons or
      oligodendrocytes. The NPCs-derived astrocytes from WT but not IL-1rKO mice
      displayed co-localization of GFAP with the IL-1RI. Four to twelve weeks post
      transplantation, memory functioning was examined in the fear-conditioning and the
      water maze paradigms and LTP of perforant path-dentate gyrus synapses was
      assessed in anesthetized mice. As expected, IL-1rKO mice transplanted with IL
      1rKO cells or sham operated displayed severe memory disturbances in both
      paradigms as well as a marked impairment in LTP. In contrast, IL-1rKO mice
      transplanted with WT NPCs displayed a complete rescue of the impaired memory
      functioning as well as partial restoration of LTP. These findings indicate that
      astrocytes play a critical role in memory functioning and LTP, and specifically
      implicate astrocytic IL-1 signaling in these processes. The results suggest novel
      conceptualization and therapeutic targets for neuropsychiatric disorders
      characterized by impaired astrocytic functioning concomitantly with disturbed
      memory and synaptic plasticity.

PMID- 21093582
TI  - Distribution of orexinergic neurons and their terminal networks in the brains of
      two species of African mole rats.
AB  - The distribution of orexinergic cell bodies and terminal networks within the
      brains of two species of African mole rat (Cape-dune mole rat--Bathyergus suillus
      and highveld mole rat--Cryptomys hottentotus) were identified using
      immunohistochemistry for orexin-A. The aim of the study was to investigate
      possible differences in the nuclear complement and terminal distribution of this
      system by comparing those of the mole rats to published studies of other rodents
      and mammals. The wild-caught mole rats used in this study live a subterranean
      lifestyle and are well known for their regressed visual system, which may lead to
      the prediction of differences in the distribution of the cell bodies and the
      terminal networks; however, we found that both species of mole rat displayed
      orexinergic nuclei limited to the hypothalamus in regions similar to those
      previously reported for other rodent and mammalian species. No immunoreactive
      neurons could be identified, in either species of mole rat within the anterior
      hypothalamic paraventricular nucleus, as has been reported for Murid rodents. The
      terminal networks, while remaining similar between the species, are more strongly
      expressed in the Cape-dune mole rat than in the highveld mole rat.

PMID- 21093581
TI  - Developmental dioxin exposure of either parent is associated with an increased
      risk of preterm birth in adult mice.
AB  - We have previously described diminished uterine progesterone response and
      increased uterine sensitivity to inflammation in adult female mice with a history
      of developmental exposure to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). Since
      parturition in mammals is an inflammatory process mediated in part by a decline
      in progesterone action, toxicant-mediated disruption of progesterone receptor
      (PR) expression at the maternal-fetal interface would likely impact the timing of
      birth. Therefore, in the current study, we examined pregnancy outcomes in adult
      female mice with a similar in utero exposure to TCDD. We also examined the impact
      of in utero TCDD exposure of male mice on pregnancy outcomes in unexposed females
      since the placenta, a largely paternally derived organ, plays a major role in the
      timing of normal parturition via inflammatory signaling. Our studies indicate
      that developmental exposure of either parent to TCDD is associated with preterm
      birth in a subsequent adult pregnancy due to altered PR expression and placental
      inflammation.

PMID- 21093583
TI  - Projections of calcitonin gene-related peptide immunoreactive neurons in the
      vagal ganglia of the rat.
AB  - We have studied the connections of calcitonin gene-related peptide immunoreactive
      (CGRP-ir) sensory neurons in the ganglia of the vagus nerve. Many CGRP-ir neurons
      were identified in the jugular ganglion located in the cranial cavity, while
      fewer CGRP-ir neurons were found in the nodose ganglion located at the level of
      the jugular foramen. Application of Fluorogold to the cut end of the cervical
      vagus nerve resulted in many Fluorogold-labeled neurons in both the jugular and
      the nodose ganglia. Application of Fluorogold to the cut end of the
      subdiaphragmatic vagus nerve resulted in Fluorogold-labeled neurons mostly in the
      nodose ganglion with only a few labeled neurons in the jugular ganglion.
      Injection of Fluorogold into the heart resulted in Fluorogold-labeled neurons in
      both the jugular and the nodose ganglia. Double labeling combining CGRP
      immunohistochemistry and Fluorogold retrograde tracing showed that in cases of
      both the application of Fluorogold to the cut end of the cervical vagus nerve and
      the injection of Fluorogold into the heart, about 40% of the Fluorogold-labeled
      neurons in the jugular ganglion expressed CGRP-like immunoreactivity. These
      results indicate that many CGRP-ir neurons in the jugular ganglion innervate the
      cervical and thoracic visceral organs, including the heart, but only a few CGRP
      ir neurons project to the abdominal visceral organs.

PMID- 21093584
TI  - Zebrafish wnt9a is expressed in pharyngeal ectoderm and is required for palate
      and lower jaw development.
AB  - Wnt activity is critical in craniofacial morphogenesis. Dysregulation of Wnt/beta
      catenin signaling results in significant alterations in the facial form, and has
      been implicated in cleft palate phenotypes in mouse and man. In zebrafish, we
      show that wnt9a is expressed in the pharyngeal arch, oropharyngeal epithelium
      that circumscribes the ethmoid plate, and ectodermal cells superficial to the
      lower jaw structures. Alcian blue staining of morpholino-mediated knockdown of
      wnt9a results in loss of the ethmoid plate, absence of lateral and posterior
      parachordals, and significant abrogation of the lower jaw structures. Analysis of
      cranial neural crest cells in the sox10:eGFP transgenic demonstrates that the
      wnt9a is required early during pharyngeal development, and confirms that the
      absence of Alcian blue staining is due to absence of neural crest derived
      chondrocytes. Molecular analysis of genes regulating cranial neural crest
      migration and chondrogenic differentiation suggest that wnt9a is dispensable for
      early cranial neural crest migration, but is required for chondrogenic
      development of major craniofacial structures. Taken together, these data
      corroborate the central role for Wnt signaling in vertebrate craniofacial
      development, and reveal that wnt9a provides the signal from the pharyngeal
      epithelium to support craniofacial chondrogenic morphogenesis in zebrafish.

PMID- 21093585
TI  - Foxa1 and Foxa2 positively and negatively regulate Shh signalling to specify
      ventral midbrain progenitor identity.
AB  - Foxa2, a member of the Foxa family of forkhead/winged helix family of
      transcription factors, has previously been shown to be an upstream positive
      regulator of Shh expression in many different tissues. Recent studies also
      strongly suggest that Foxa2 specify cell fate by inhibiting the expression of
      cell fate determinants such as Helt1 and Nkx2.2. In this paper, phenotypic
      analyses of Wnt1cre; Foxa2flox/flox embryos in the midbrain have demonstrated a
      novel role for Foxa2 and its related family member, Foxa1, to attenuate Shh
      signalling by inhibiting the expression of its intracellular transducer, Gli2, at
      the transcriptional level. Chromatin immunoprecipitation experiments indicate
      that Foxa2 binds to genomic regions of Gli2 and likely regulates its expression
      in a direct manner. Our studies, involving loss and gain of function studies in
      mice, also provided further insights into the gene regulatory interactions among
      Foxa1, Foxa2 and Shh in ventral midbrain progenitors that contribute to midbrain
      patterning. Altogether, these data indicate that Foxa1 and Foxa2 contribute to
      the specification of ventral midbrain progenitor identity by regulating Shh
      signalling in a positive and negative manner.

PMID- 21093586
TI  - Nanoparticles attenuate P-glycoprotein/MDR1 function in A549 human alveolar
      epithelial cells.
AB  - P-glycoprotein/MDR1 (P-gp) is a well-characterised membrane transporter relevant
      in drug disposition and multi-drug resistance. In this study, we aimed to
      investigate how far nanoparticulates impair the function of the P-gp transport
      system and which particle properties govern these interactions. Expression and
      function of P-gp was confirmed in A549 cell monolayers. Rhodamine 123 (Rh123)
      release studies were carried out in the presence of known inhibitors of P-gp
      function (i.e., cyclosporine A and verapamil), under ATP depletion (NaN(3)/DOG)
      and after acute exposure to nanoparticles (NPs) with different surface
      modifications, zeta-potentials and sizes (plain, carboxylated, and amine- and
      sulphate-modified). The cytotoxic potential of NPs on A549 monolayers was
      evaluated by MTT assay. The effects on P-gp protein level, after incubation with
      NPs, were investigated by Western blot analysis of A549 cell lysate and
      supernatant. Cellular retention of Rh123 was significantly (P<0.05) increased in
      the presence of carboxylated (100 nm), amine- and sulphate-modified NPs. A
      slight, but not significant, decrease in Rh123 release was also observed for
      plain latex and carboxylated (500 nm) NPs. The MTT assay demonstrated that most
      NPs caused only marginal levels of cytotoxicity (78-88% cell viability); the
      positively charged amine-NPs, however, were considerably more cytotoxic. Western
      blot showed that NPs did not cause any cell membrane disruption. Our findings
      suggest that nanomaterials can attenuate membrane transporter function depending
      on their size and surface properties and hence might influence the disposition of
      xenobiotics as well as endogenous substrates.

PMID- 21093588
TI  - Polyethylenimines for RNAi-mediated gene targeting in vivo and siRNA delivery to
      the lung.
AB  - RNA interference (RNAi) is a promising strategy to inhibit the expression of
      pathologically relevant genes, which show aberrant (over-)expression, e.g. in
      tumors or other pathologies. The induction of RNAi relies on small interfering
      RNAs (siRNAs), which trigger the specific mRNA degradation. Their instability and
      poor delivery into target tissues including the lung, however, so far severely
      limits the therapeutic use of siRNAs and requires the development of nanoscale
      delivery systems. Polyethylenimines (PEIs) are synthetic polymers, which are able
      to form non-covalent complexes with siRNAs. These nanoscale complexes
      ('nanoplexes') allow the protection of siRNAs from nucleolytic degradation, their
      efficient cellular uptake through endocytosis and intracellular release through
      the 'proton sponge effect'. Chemical modifications of PEIs as well as the
      coupling of cell/tissue-specific ligands are promising approaches to increase the
      biocompatibility, specificity and efficacy of PEI-based nanoparticles. This
      review article gives a comprehensive overview of pre-clinical in vivo studies on
      the PEI-mediated delivery of therapeutic siRNAs in various animal models. It
      discusses the chemical properties of PEIs and PEI modifications, and their
      influences on siRNA knockdown efficacy, on adverse effects of the polymer or the
      nanoplex and on siRNA biodistribution in vivo. Beyond systemic application, PEI
      based complexation allows the local siRNA application to the lung.
      Biodistribution studies demonstrate cellular uptake of PEI-complexed, but not of
      naked siRNAs in the lung with little systemic availability of the siRNAs,
      indicating the usefulness of this approach for the targeting of genes, which are
      pathologically relevant in lung tumors or lung metastases. Taken together, (i)
      PEI and PEI derivatives may represent an efficient delivery platform for siRNAs,
      (ii) siRNA-mediated induction of RNAi is a promising approach for the knockdown
      of pathologically relevant genes, and (iii) when sufficiently addressing
      biocompatibility issues, the locoregional delivery of PEI/siRNA complexes may
      become an attractive therapeutic strategy for the treatment of lung diseases with
      little systemic side effects.

PMID- 21093587
TI  - Geometry and surface characteristics of gold nanoparticles influence their
      biodistribution and uptake by macrophages.
AB  - Spherical and rod-shaped gold nanoparticles with surface poly(ethylene glycol)
      (PEG) chains were characterized for size, shape, charge, poly dispersity and
      surface plasmon resonance. The nanoparticles were injected intravenously to 6-8
      week-old female nu/nu mice bearing orthotopic ovarian tumors, and their
      biodistribution in vital organs was compared. Gold nanorods were taken up to a
      lesser extent by the liver, had longer circulation time in the blood, and higher
      accumulation in the tumors, compared with their spherical counterparts. The
      cellular uptake of PEGylated gold nanoparticles by a murine macrophage-like cell
      line as a function of geometry was examined. Compared to nanospheres, PEGylated
      gold nanorods were taken up to a lesser extent by macrophages. These studies
      point to the importance of gold nanoparticle geometry and surface properties on
      transport across biological barriers.

PMID- 21093589
TI  - High loading efficiency and sustained release of siRNA encapsulated in PLGA
      nanoparticles: quality by design optimization and characterization.
AB  - Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery
      of biopharmaceuticals owing to its biocompatibility, biodegradability and
      outstanding controlled release characteristics. The purpose of this study was to
      understand and define optimal parameters for preparation of small interfering RNA
      (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation
      method and characterize their properties. The experiments were performed
      according to a 2(5-1) fractional factorial design based on five independent
      variables: The volume ratio between the inner water phase and the oil phase, the
      PLGA concentration, the sonication time, the siRNA load and the amount of
      acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to
      stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency
      and the particle size were investigated. The most important factors for obtaining
      an encapsulation efficiency as high as 70% were the PLGA concentration and the
      volume ratio whereas the size was mainly affected by the PLGA concentration. The
      viscosity of the oil phase was increased at high PLGA concentration, which
      explains the improved encapsulation by stabilization of the primary emulsion and
      reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased
      the encapsulation efficiency at low PLGA concentrations. The PLGA matrix
      protected siRNA against nuclease degradation, provided a burst release of surface
      localized siRNA followed by a triphasic sustained release for two months. These
      results enable careful understanding and definition of optimal process parameters
      for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with
      immediate and long-term sustained release properties.

PMID- 21093591
TI  - Pleiotropic actions of fenofibrate on the heart.
AB  - Fenofibrate is a third-generation fibric acid derivative employed clinically as a
      hypolipidemic agent to lessen the risk caused by atherosclerosis. Dyslipidemia is
      a condition associated with elevated levels of low-density lipoproteins (LDL),
      very low-density lipoproteins (VLDL) and triglycerides, and reduced levels of
      high-density lipoproteins (HDL) in the circulation. Fenofibrate has an ability to
      diminish LDL, VLDL and triglycerides and pertinently augment HDL, and thus it is
      used to manage dyslipidemia. The lipid lowering effects of fenofibrate are
      classically mediated via an activation of peroxisome proliferator-activated
      receptor-alpha (PPAR-alpha). Recent studies demonstrated numerous pleiotropic
      effects of fenofibrate on the heart that afford direct myocardial protection
      besides its lipid lowering effects. Fenofibrate has an additional potential to
      prevent the induction and progression of hypertensive heart damage, cardiac
      hypertrophy, heart failure, myocarditis, lipotoxic cardiomyopathy and vascular
      endothelial dysfunction-associated cardiovascular abnormalities. In this review,
      we critically discussed recently identified pleiotropic actions of fenofibrate on
      the heart. Moreover, the novel cardioprotective effects of fenofibrate against
      various cardiac disorders have been delineated.

PMID- 21093592
TI  - The 1.9A crystal structure of Prp20p from Saccharomyces cerevisiae and its
      binding properties to Gsp1p and histones.
AB  - Prp20p is the homolog of mammalian RCC1 (regulator of chromosome condensation 1)
      in Saccharomyces cerevisiae, which acts as the guanine nucleotide exchange factor
      (GEF) for Gsp1p (yeast Ran). Prp20p plays multiple roles in mRNA metabolism,
      nucleocytoplasmic transport and mitosis regulation. Prp20p also functions as a
      linker between chromatin and nuclear pore complex (NPC) which regulates the NPC
      mediated boundary activity (BA). Prp20p contains an N-terminal nuclear
      localization signal (NLS) and a typical RCC1-like domain (RLD). Here we present
      the 1.9A crystal structure of the RCC1-like domain of Prp20p, which exhibits a
      classical seven-bladed beta-propeller. We also proved that the additional beta
      wedge in Prp20p is essential for the interaction between Prp20p and Gsp1p. Based
      on this structure, we built a complex model of Prp20p and Gsp1p which was
      optimized by molecular dynamics (MD) simulations. Our model reveals that Prp20p
      and RCC1 share similar Ran GTPase binding mode. In addition, we also studied the
      histone-binding property of Prp20p in vitro.

PMID- 21093590
TI  - Chemically modified non-antimicrobial tetracyclines are multifunctional drugs
      against advanced cancers.
AB  - Metastatic cancers account for more than 90% of cancer mortality. The metastasis
      of all cancers is critically mediated by enzymes that degrade extracellular
      matrix. Aggressive tumors are characterized by an imbalance between enzymes that
      degrade ECM and endogenous inhibitors of the enzymes. Matrix metalloproteinases
      (MMPs) make up the majority of ECM degrading enzymes implicated in cancer
      metastasis. The potent MMP inhibitory activities of tetracyclines, especially
      their chemically modified analogs, combined with their relatively well tolerated
      pharmacological profile, led several researchers to investigate their anticancer
      potential in a variety of cancers, including melanoma, lung, breast and prostate
      cancers. Chemically modified non-antibiotic tetracyclines (CMTs or COL) were
      tested using tumors of prostate, breast and melanomas. Some of these CMTs,
      notably, CMT-3 and CMT-308 significantly inhibited not only invasive potential
      and MMP activity, but also inhibited cell proliferation by inducing cell cycle
      arrest and apoptosis. CMT-3 and CMT-308 were significantly more potent than
      doxycycline or minocycline in inhibiting tumor cell-derived MMPs and inducing
      apoptosis in vitro and in vivo. CMT-3 (COL-3) showed potent inhibition of tumor
      growth in xenografts and in bone metastatic models of prostate cancer. Similar
      results were also reported in melanoma and breast cancer models. The mechanism by
      which CMTs kill tumor cells is via generation of hydroxyl free radicals ([OH](-))
      which permeate and depolarize mitochondria, which in turn activates caspase
      mediated apoptosis. Analysis of tumor tissues from CMT-3 treated rats
      demonstrated reduction in angiogenesis and increase in apoptosis; both emerged as
      mechanisms of CMT action. These observations led to testing the efficacy of CMT-3
      in human clinical trials against several types of cancer with significant
      outcomes, which are described in the next chapter of this issue.

PMID- 21093593
TI  - The differential dynamics of antibody subpopulation expression during affinity
      maturation in a teleost.
AB  - A compositional analysis of the antibody response in rainbow trout was conducted
      using an affinity-based immunopartitioning assay. Trout were immunized with TNP
      keyhole limpet hemocyanin (TNP-KLH) and individual serum titers and their
      affinity distributions analyzed over a period of 27 weeks. The kinetics of
      antibody affinity subpopulation development revealed certain key features: 1) the
      lowest affinity subpopulation (log aK, 3.5-3.99) appears early, does not achieve
      high titer, and was more transient than the higher affinity subpopulations; 2)
      intermediate affinity subpopulations (log aK, 5.0-5.99) appear later (week 5),
      achieve relatively high titers and persist longer; and 3) the highest affinity
      subpopulations (log aK, 6.0-7.49) emerge much later (post week 15), and have
      comparable titers to the intermediate affinity group. We find that the affinity
      maturation of the serum antibody response can be resolved into each affinity
      subpopulation's contribution both in quantity and timing.

PMID- 21093594
TI  - Atlas of transgenic Tet-Off Ca2+/calmodulin-dependent protein kinase II and prion
      protein promoter activity in the mouse brain.
AB  - Conditional transgenic mouse models are important tools for investigations of
      neurodegenerative diseases and evaluation of potential therapeutic interventions.
      A popular conditional transgenic system is the binary tetracycline-responsive
      gene (Tet-Off) system, in which the expression of the gene of interest depends on
      a tetracycline-regulatable transactivator (tTA) under the control of a specific
      promoter construct. The most frequently used Tet-Off promoter mouse lines are the
      Ca(2+)/calmodulin-dependent protein kinase II (CamKII) and prion protein (PrP)
      promoter lines, respectively. To target the regulated gene of interest to
      relevant brain regions, a priori knowledge about the spatial distribution of the
      regulated gene expression in the brain is important. Such distribution patterns
      can be investigated using double transgenic mice in which the promoter construct
      regulates a LacZ reporter gene encoding the marker beta-galactosidase which can
      be histologically detected using its substrate X-gal. We have previously
      published an atlas showing the brain-wide expression mediated by the Tet-Off PrP
      promoter mouse line, but the distribution of activity in the Tet-Off CamKII
      promoter mouse line is less well known. To compare promoter activity
      distributions in these two Tet-Off mouse lines, we have developed an online
      digital atlas tailored for side-by-side comparison of histological section
      images. The atlas provides a comprehensive list of brain regions containing X-gal
      labeling and an interactive dual image viewer tool for panning and zooming of
      corresponding section images. Comparison of spatial expression patterns between
      the two lines show considerable regional and cellular differences, relevant in
      context of generation and analysis of inducible models based on these two
      tetracycline responsive promoter mouse lines.

PMID- 21093595
TI  - Experiential, autonomic, and neural responses during threat anticipation vary as
      a function of threat intensity and neuroticism.
AB  - Anticipatory emotional responses play a crucial role in preparing individuals for
      impending challenges. They do this by triggering a coordinated set of changes in
      behavioral, autonomic, and neural response systems. In the present study, we
      examined the biobehavioral impact of varying levels of anticipatory anxiety,
      using a shock anticipation task in which unpredictable electric shocks were
      threatened and delivered to the wrist at variable intervals and intensities
      (safe, medium, strong). This permitted investigation of a dynamic range of
      anticipatory anxiety responses. In two studies, 95 and 51 healthy female
      participants, respectively, underwent this shock anticipation task while
      providing continuous ratings of anxiety experience and electrodermal responding
      (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step
      wise pattern of responding in anxiety experience and electrodermal responses.
      Several brain regions showed robust responses to shock anticipation relative to
      safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral
      gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of
      these regions demonstrated a linear pattern of increased responding from safe to
      medium to strong trials, including the bilateral insula, ACC, and inferior
      frontal gyrus. These responses were modulated by individual differences in
      neuroticism, such that those high in neuroticism showed exaggerated anxiety
      experience across the entire task, and reduced brain activation from medium to
      strong trials in a subset of brain regions. These findings suggest that
      individual differences in neuroticism may influence sensitivity to anticipatory
      threat and provide new insights into the mechanism through which neuroticism may
      confer risk for developing anxiety disorders via dysregulated anticipatory
      responses.

PMID- 21093596
TI  - In vitro hippocampal gamma oscillation power as an index of in vivo CA3 gamma
      oscillation strength and spatial reference memory.
AB  - Neuronal synchronisation at gamma frequencies (30-100 Hz) has been implicated in
      cognition and memory. Gamma oscillations can be studied in various in vitro
      models, but their in vivo validity and their relationship with reference memory
      remains to be proven. By using the natural variation of wild type C57bl/6J mice,
      we assessed the relationships between reference memory and gamma oscillations
      recorded in hippocampal area CA3 in vivo and in vitro. Local field potentials
      (LFPs) were recorded from area CA3 in behaviourally-characterised freely moving
      mice, after which hippocampal slices were prepared for recordings in vitro of
      spontaneous gamma oscillations and kainate-induced gamma oscillations in CA3. The
      gamma-band power of spontaneous oscillations in vitro correlated with that of CA3
      LFP oscillations during inactive behavioural states. The gamma-band power of
      kainate-induced oscillations correlated with the activity-dependent increase in
      CA3 LFP gamma-band power in vivo. Kainate-induced gamma-band power correlated
      with Barnes circular platform performance and object location recognition, but
      not with object novelty recognition. Kainate-induced gamma-band power was larger
      in mice that recognised the aversive context, but did not correlate with passive
      avoidance delay. The correlations between behavioural and electrophysiological
      measures obtained from the same animals show that the gamma-generating capacity
      of the CA3 network in vitro is a useful index of in vivo gamma strength and
      supports an important role of CA3 gamma oscillations in spatial reference memory.

PMID- 21093597
TI  - The central amygdala nucleus via corticotropin-releasing factor is necessary for
      time-limited consolidation processing but not storage of contextual fear memory.
AB  - The central nucleus of the amygdala (CeA) is traditionally portrayed in fear
      conditioning as the key neural output that relays conditioned information
      established in the basolateral amygdala complex to extra-amygdalar brain
      structures that generate emotional responses. However, several recent studies
      have questioned this serial processing view of the amygdalar fear conditioning
      circuit by showing an influence of the CeA on memory consolidation. We previously
      reported that inhibition of endogenous CeA secretion of corticotropin-releasing
      factor (CRF) at the time of contextual training effectively impaired fear memory
      consolidation. However, the time-dependent range of CeA CRF secretion in
      facilitating consolidation processing has not been examined. Therefore, to
      address this issue, we performed CeA site-specific microinjections of CRF
      antisense oligonucleotides (CRF ASO) at several post-training time intervals.
      Rats microinjected with CRF ASO at post-training intervals up to 24-h
      subsequently exhibited significant impairments in contextual freezing retention
      in contrast to animals treated 96-h after training. To further establish the
      validity of the results, CeA fiber-sparing lesions were made at two distinct post
      training periods (24-h and 96-h), corresponding respectively to the temporal
      intervals when CeA CRF ASO administration disrupted or had no significant effects
      on memory consolidation. Similar to the CeA CRF ASO results, CeA lesions made 24
      h, but not 96-h, after training induced significant freezing deficits in the
      retention test. In conclusion, the current results demonstrate: (1) an extended
      involvement of CeA CRF in contextual memory consolidation and (2) that contextual
      fear memory storage is not dependent on a functional CeA.

PMID- 21093599
TI  - High-fat diets impair spatial learning in the radial-arm maze in mice.
AB  - It has been suggested that hyperglycemia and insulin resistance triggered by
      energy-dense diets can account for hippocampal damage and deficits of cognitive
      behaviour. We wonder if the impairment of learning and memory processes detected
      in diet-induced obese (DIO) mice is linked to diet composition itself. With this
      purpose we have evaluated learning performance in mice undergoing a short-term
      high-fat (HF) treatment, which leads to a pre-obese state characterized by
      increased adiposity without significant changes of glucose and insulin plasma
      levels. C57BL/6J mice were fed either a HF (45 kcal% from fat) or control diet
      (10 kcal% from fat) during 8 weeks. Learning performance was evaluated by using
      the four-arm baited version of the eight-arm radial maze test (RAM). Mice were
      trained to learn the RAM protocol and then memory was tested at different time
      points. Time spent to consume food placed in baited arms and errors committed to
      find them were measured in all sessions. DIO mice significantly spent more time
      in learning the task and made a greater number of errors than controls. Moreover,
      retention tests revealed that both working and total memory errors were also more
      numerous in DIO mice. The current results show that short-term DIO impairs
      spatial learning and suggest that impairment of hippocampal learning elicited by
      HF diets might be perceptible before metabolic alterations linked to obesity
      develop.

PMID- 21093598
TI  - Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats.
AB  - Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of
      learning processes and is important for inhibitory avoidance and conditioned
      taste aversion learning. MGlu5 receptors are physically connected with NMDA
      receptors and they interact with, and modulate, the function of one another in
      several brain regions. The present studies used systemic co-administration of an
      mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol
      5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK
      801) to characterize the interactions of these receptors in two aversive learning
      tasks. Male Sprague-Dawley rats were trained in a single-trial step-down
      inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10mg/kg,
      s.c.), delivered by itself prior to the conditioning trial, did not have any
      effect on performance in either task 48 h after training. However, CDPPB (at
      3mg/kg) attenuated the MK-801 (0.2mg/kg, i.p.) induced learning deficit in both
      tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie
      the importance of mGlu5 and NMDA receptor interactions in modulating memory
      processing, and are consistent with findings showing the efficacy of positive
      allosteric modulators of mGlu5 receptors in reversing the negative effects of
      NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor
      gating, or working, spatial and recognition memory.

PMID- 21093600
TI  - Primary CNS lymphoma--radiation-free salvage therapy by second autologous stem
      cell transplantation.

PMID- 21093601
TI  - Helicobacter pylori infection and graft-versus-host disease.
AB  - The gastrointestinal (GI) tract is the main target site of graft-versus-host
      disease (GVHD). Diagnosis is based on endoscopic and histological findings.
      Helicobacter pylori (HP) is a Gram-negative spiral bacterium linked to gastritis,
      peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and
      adenocarcinoma and is frequently observed on endoscopy in patients who have
      undergone transplantation. The role, if any, played by HP infection in the
      development of acute GVHD is unknown. We conducted a retrospective study between
      January 1, 1990, and December 31, 2008, of 338 upper GI endoscopies
      (gastroscopies) performed on patients who underwent allogeneic stem cell
      transplantation with clinical suspicion of GVHD (198 patients). Acute and chronic
      GVHD were confirmed from histological features in 97 patients (51.3%) and 68
      patients (36%), respectively. HP infection was detected in 69 patients (35%) and
      had a negative modulating effect on the development of acute GVHD (relative risk
      [RR], 0.60; 95% confidence interval, 0.46-0.79; P = .001) and chronic GVHD (RR,
      0.75; 95% confidence interval, 0.61-0.92; P = .016). Furthermore, the presence of
      HP was inversely correlated with the histological severity of GVHD (P = .003).
      Our findings suggest that infection with HP may have a negative modulating effect
      on GVHD.

PMID- 21093603
TI  - The immunity and protective effects of antigen 85A and heat-shock protein X
      against progressive tuberculosis.
AB  - The anti-tuberculosis vaccine, Mycobacterium bovis BCG, has been used worldwide,
      but its protective efficacy is variable against adult pulmonary tuberculosis. In
      this study, immune responses of antigen 85A (Ag85A) and heat-shock protein X
      (HspX) antigen of Mycobacterium tuberculosis were investigated during acute and
      stationary stage of infection in the murine aerosol TB challenge model and their
      protective effects were evaluated against progressive tuberculosis. A high level
      of Ag85A-specific IFN-gamma production was induced from the early stage of the
      infection, whereas HspX-specific IFN-gamma production was increased in the later
      stationary stage. As a subunit vaccine, Ag85A and HspX antigen vaccine induced
      high levels of IFN-gamma, and a vaccine comprising both antigens induced the
      highest level of IFN-gamma. At 30 days post-challenge, the Ag85A subunit vaccine
      was protective against M. tuberculosis challenge, but the HspX subunit vaccine
      was not. Interestingly, the HspX antigen vaccine induced significant protective
      efficacy at 90 days post-challenge. Moreover, the combined antigen vaccine
      induced the highest protective efficacy against M. tuberculosis challenge both at
      30 days and 90 days post-challenge. These results suggest that the vaccine
      comprising Ag85A and HspX antigen which react in different stages of infection is
      highly protective against progressive tuberculosis.

PMID- 21093602
TI  - Molecular pharmacology in a simple model system: implicating MAP kinase and
      phosphoinositide signalling in bipolar disorder.
AB  - Understanding the mechanisms of drug action has been the primary focus for
      pharmacological researchers, traditionally using rodent models. However, non
      sentient model systems are now increasingly being used as an alternative approach
      to better understand drug action or targets. One of these model systems, the
      social amoeba Dictyostelium, enables the rapid ablation or over-expression of
      genes, and the subsequent use of isogenic cell culture for the analysis of cell
      signalling pathways in pharmacological research. The model also supports an
      increasingly important ethical view of research, involving the reduction,
      replacement and refinement of animals in biomedical research. This review
      outlines the use of Dictyostelium in understanding the pharmacological action of
      two commonly used bipolar disorder treatments (valproic acid and lithium). Both
      of these compounds regulate mitogen activated protein (MAP) kinase and inositol
      phospholipid-based signalling by unknown means. Analysis of the molecular
      pathways targeted by these drugs in Dictyostelium and translation of discoveries
      to animal systems has helped to further understand the molecular mechanisms of
      these bipolar disorder treatments.

PMID- 21093604
TI  - Identification of major clonal complexes and toxin producing strains among
      Staphylococcus aureus associated with atopic dermatitis.
AB  - Staphylococcus aureus promotes the onset and severity of atopic dermatitis (AD),
      which is exacerbated by superantigen toxins SEB and SEC. The genetic identity of
      these isolates, and their relationship to common hospital- or community
      associated methicillin resistant S. aureus (HA-MRSA and CA-MRSA) has not been
      defined. We conducted spa typing, partial multi-locus sequence typing (MLST), and
      toxin profiling (seb, sec, lukS-PV) of S. aureus from 119 pediatric and 40 adult
      AD patients. MLST clonal complexes CC45, CC5, CC15, CC1, CC8 and CC30 accounted
      for 79% of isolates, representing the same major groups reported for nosocomial
      S. aureus in hospital intensive care units. The highest disease severity was
      associated with CC1, which was significantly greater relative to CC15 (p = 0.017)
      or CC30 (p = 0.040), but with no significant difference relative to CC45, CC5 or
      CC8. Although there were two few lukS-PV, seb or sec isolates to infer a role in
      disease severity, CC45 was identified as a source of SEC producing strains, and
      lukS-PVL was associated with a small number of CC5 pediatric isolates. CC1
      harbored the only CA-MRSA that was identified, and was a source of isolates that
      expressed both seb and sec, and closely resembled the USA400 strain of CA-MRSA.

PMID- 21093605
TI  - Effect of resveratrol and quercetin in experimental infection by Salmonella
      enterica serovar Typhimurium.
AB  - Flavonoids are phenolic compounds widely distributed in almost every plant and
      act as pharmacologically active constituents in many herbal medicines. They have
      multiple biological, pharmacological, and medicinal properties including anti
      inflammatory and cytoprotective effects. In the present study, the experiments
      were performed to evaluate the effect of resveratrol and quercetin on
      proliferation, viability, nitric oxide (NO) production, and apoptosis in
      Salmonella enterica serovar Typhimurium-infected U937 cells and monocytes (MN).
      The results showed in a time- and dose-dependent manner that both resveratrol and
      quercetin reduced S. enterica serovar Typhimurium-induced NO production. In
      addition, the vegetable extracts resveratrol and quercetin inhibited cell
      viability and proliferation in S. enterica serovar Typhimurium-infected cells. S.
      enterica serovar Typhimurium-induced apoptosis was also blocked by resveratrol
      and quercetin. The results obtained indicate that flavonoids modulate the host
      response during salmonellosis by protecting the host cells from the toxic effects
      of bacterial infection and also by decreasing programmed cell death. Hence, these
      polyphenols can be considered potential candidates against S. enterica serovar
      Typhimurium-related gastric pathogenic processes, and further attention should be
      given to their application as a treatment for infectious diseases.

PMID- 21093606
TI  - All creatures great and small: regulatory T cells in mice, humans, dogs and other
      domestic animal species.
AB  - Abnormalities of peripheral tolerance are thought to contribute to the
      pathogenesis of a number of inflammatory, autoimmune and neoplastic diseases of
      both humans and animals. Furthermore, the induction of allograft tolerance is the
      'holy grail' of clinical transplantation. Of the various mechanisms underlying
      peripheral tolerance, regulatory T cells (Tregs) have risen to particular
      prominence. Various Treg subsets have been characterised, including naturally
      occurring cells that develop along a regulatory lineage in the thymus and induced
      cells that arise in the periphery from conventional T cell precursors. The
      transcription factor Forkhead box (Foxp3) serves a crucial role in stabilising
      the Treg transcriptome and is a faithful marker of peripheral Tregs in the mouse,
      though its expression is somewhat more promiscuous in man. Regulatory T cells
      display a wide spectrum of suppressive and cytotoxic mechanisms and may convert
      to specific T helper cell subsets in response to appropriate inflammatory cues.
      Although knowledge of Tregs in domestic animal species is still in its infancy, a
      growing body of literature is accumulating in the dog, cat, pig, cow, sheep and
      horse. We highlight our own and other studies of Tregs in the dog, an important
      veterinary species and a model for a number of human diseases. The ethos of 'One
      Health, One Medicine' is anticipated to accelerate efforts to close the knowledge
      gap between domestic animal and mainstream species in this field. We predict that
      the prodigious pace of research into Tregs will continue unabated for years to
      come, fuelled by the exciting therapeutic potential of these cells.

PMID- 21093607
TI  - Effect of divalent cations on the porcine kidney cortex membrane-bound form of
      dipeptidyl peptidase IV.
AB  - Dipeptidyl peptidase IV is an ectopeptidase with multiple physiological roles
      including the degradation of incretins, and a target of therapies for type 2
      diabetes mellitus. Divalent cations can inhibit its activity, but there has been
      little effort to understand how they act. The intact membrane-bound form of
      porcine kidney dipeptidyl peptidase IV was purified by a simple and fast
      procedure. The purified enzyme hydrolyzed Gly-Pro-p-nitroanilide with an average
      V(max) of 1.397+/-0.003 MUmol min(-1) mL(-1), k(cat) of 145.0+/-1.2 s(-1), K(M)
      of 0.138+/-0.005 mM and k(cat)/K(M) of 1050 mM(-1) s(-1). The enzyme was
      inhibited by bacitracin, tosyl-L-lysine chloromethyl ketone, and by the
      dipeptidyl peptidase IV family inhibitor L-threo-Ile-thiazolidide (K(i) 70 nM).
      The enzyme was inhibited by the divalent ions Ca(2+), Co(2+), Cd(2+), Hg(2+) and
      Zn(2+), following kinetic mechanisms of mixed inhibition, with K(i) values of
      2.04*10(-1), 2.28*10(-2), 4.21*10(-4), 8.00*10(-5) and 2.95*10(-5) M,
      respectively. According to bioinformatic tools, Ca(2+) ions preferentially bound
      to the beta-propeller domain of the porcine enzyme, while Zn(2+) ions to the
      alpha-beta hydrolase domain; the binding sites were strikingly conserved in the
      human enzyme and other homologues. The functional characterization indicates that
      porcine and human homologues have very similar functional properties. Knowledge
      about the mechanisms of action of divalent cations may facilitate the design of
      new inhibitors.

PMID- 21093608
TI  - Characterization of protein therapeutics by mass spectrometry: recent
      developments and future directions.
AB  - Mass spectrometry (MS) has become a powerful technology in the discovery and
      development of protein therapeutics in the biopharmaceutical industry. This
      review article describes recent developments and future trends in the
      characterization of protein therapeutics using MS. We discuss top-down MS for the
      characterization of protein modifications, hydrogen/deuterium exchange MS and ion
      mobility MS methods for higher order protein structure studies. Quantitative
      analysis of protein therapeutics (in vivo) by MS as an orthogonal approach to
      immunoassay for pharmacokinetics studies will also be illustrated.

PMID- 21093609
TI  - Chemical probes for biological systems.
AB  - According to the latest definition in use by the NIH Molecular Libraries
      Screening Centers Network, a compound to be nominated as a chemical probe should
      have, on the one hand, an affinity below 100 nM for the primary target and, on
      the other hand, at least tenfold selectivity against related targets. Taking
      drugs as the ultimate product of an affinity and selectivity optimization
      process, it is found that only 14.4% of them would actually qualify as chemical
      probes under those criteria. Therefore, if chemical probes are expected to give
      rise to new medicines, strict adherence to the current probe definition might
      result in many compounds of potential therapeutic interest being overlooked.

PMID- 21093610
TI  - Transmitral isthmus conduction alternans.

PMID- 21093611
TI  - The incidence and prognostic significance of new-onset atrial fibrillation in
      patients with acute myocardial infarction and left ventricular systolic
      dysfunction: a CARISMA substudy.
AB  - BACKGROUND: The incidence and risk associated with new-onset atrial fibrillation
      (AF) occurring after discharge in patients with acute myocardial infarction (MI)
      remains unknown. OBJECTIVE: This study sought to describe the incidence and
      clinical risk associated with postdischarge new-onset AF in post-MI patients with
      left ventricular systolic dysfunction. METHODS: The population included 271 post
      MI patients with left ventricular ejection fraction <= 40% and no history of
      previous AF from the Cardiac Arrhythmias and Risk Stratification after Acute
      Myocardial Infarction (CARISMA) study. All patients were implanted with an
      implantable cardiac monitor and followed up every 3 months for 2 years. Major
      cardiovascular events were defined as reinfarction, stroke, hospitalization for
      heart failure, or death. RESULTS: The risk of new-onset AF is highest during the
      first 2 months after the acute MI (16% event rate) and decreases until month 12
      post-MI, after which the risk for new-onset AF is stable. The risk of major
      cardiovascular events was increased in patients with AF events >= 30 seconds
      (hazard ratio [95% CI] = 2.73 [1.35 to 5.50], P = .005), but not in patients with
      AF events lasting <30 seconds (hazard ratio [95% CI] = 1.17 [0.35 to 3.92], P =
      .80). More than 90% of all recorded AF events were asymptomatic. CONCLUSION:
      Using an implantable cardiac monitor, the incidence of new-onset AF was found to
      be 4-fold higher than earlier reported. In the study population, in which
      treatment with beta-blockers was optimized, the vast majority of AF events were
      asymptomatic, emphasizing the importance of using continuous monitoring for
      studies concerning AF in heart failure patients. A duration of 30 seconds or more
      identified clinically important AF episodes documented by an implantable cardiac
      monitor.

PMID- 21093612
TI  - Global population structure of the stable fly (Stomoxys calcitrans) inferred by
      mitochondrial and nuclear sequence data.
AB  - Stomoxys calcitrans (Diptera: Muscidae: Stomoxyini), a synanthropic fly with a
      worldwide distribution, is recognized to have an important medical and veterinary
      impact. We conducted a phylogeographic analysis based on several populations from
      five major zoogeographic regions of the world in order to analyse population
      genetic structure of S. calcitrans and to trace its global dispersion. Results
      from mitochondrial (COI, Cyt-b and ND1-16S) and nuclear (ITS2) DNA show a
      substantial differentiation of Oriental populations (first lineage) from the
      Afrotropical, Palearctic, Nearctic, Neotropical and Oceanian populations (second
      lineage). The divergence time analyses suggest the separation between the two
      lineages approximately in mid-Pleistocene. Oriental populations are isolated and
      would not have participated in the colonization of other regions, unlike the
      Afrotropical one which seems to be the source of S. calcitrans dispersion towards
      other regions. Demographic analyses indicate that Oriental, Afrotropical and
      Palearctic regions have undergone a population expansion during late Pleistocene
      early Holocene. The expansion time of this cosmopolitan species could have been
      influenced by continental human expansions and by animal domestication.

PMID- 21093613
TI  - Identification of key mechanisms controlling gene expression in Leishmania
      infected macrophages using genome-wide promoter analysis.
AB  - The present study describes the in silico prediction of the regulatory network of
      Leishmania infected human macrophages. The construction of the gene regulatory
      network requires the identification of Transcription Factor Binding Sites (TFBSs)
      in the regulatory regions (promoters, enhancers) of genes that are regulated upon
      Leishmania infection. The promoters of human, mouse, rat, dog and chimpanzee
      genes were first identified in the whole genomes using available experimental
      data on full length cDNA sequences or deep CAGE tag data (DBTSS, FANTOM3,
      FANTOM4), mRNA models (ENSEMBL), or using hand annotated data (EPD, TRANSFAC). A
      phylogenetic footprinting analysis and a MATCH analysis of the promoter sequences
      were then performed to predict TFBS. Then, an SQL database that integrates all
      results of promoter analysis as well as other genome annotation information
      obtained from ENSEMBL, TRANSFAC, TRED (Transcription Regulatory Element
      Database), ORegAnno and the ENCODE project, was established. Finally publicly
      available expression data from human Leishmania infected macrophages were
      analyzed using the genome-wide information on predicted TFBS with the computer
      system ExPlainTM. The gene regulatory network was constructed and activated
      signal transduction pathways were revealed. The Irak1 pathway was identified as a
      key pathway regulating gene expression changes in Leishmania infected
      macrophages.

PMID- 21093614
TI  - Phylogeography of foot-and-mouth disease virus types O and A in Malaysia and
      surrounding countries.
AB  - Foot-and-mouth disease (FMD) is endemic in the countries of mainland Southeast
      Asia where it represents a major obstacle to the development of productive animal
      industries. The aim of this study was to use genetic data to determine the
      distribution of FMD virus (FMDV) lineages in the Southeast Asia region, and in
      particular identify possible sources of FMDV causing outbreaks in Malaysia.
      Complete VP1 sequences, obtained from 214 samples collected between 2000 and
      2009, from FMD outbreaks in six Southeast Asian countries, were compared with
      sequences previously reported. Phylogenetic analysis of these sequences showed
      that there were two patterns of FMDV distribution in Malaysia. Firstly, for some
      lineages (O/SEA/Mya98 and serotype A), outbreaks occurred every year in the
      country and did not appear to persist, suggesting that these incursions were
      quickly eradicated. Furthermore, for these lineages FMD viruses in Malaysia were
      closely related to those from neighbouring countries, demonstrating the close
      epidemiological links between countries in the region. In contrast, for O/ME
      SA/PanAsia lineage, viruses were introduced and remained to cause outbreaks in
      subsequent years. In particular, the recent incursion and maintenance of the
      PanAsia-2 sublineage into Malaysia appears to be unique and independent from
      other outbreaks in the region. This study is the first characterisation of FMDV
      in Malaysia and provides evidence for different epidemiological sources of virus
      introduction into the country.

PMID- 21093615
TI  - Carotid chemoafferent activity is not necessary for all phrenic long-term
      facilitation following acute intermittent hypoxia.
AB  - Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity induced
      by acute intermittent hypoxia (AIH) or episodic carotid chemoafferent neuron
      activation. Surprisingly, residual pLTF is expressed in carotid denervated rats.
      However, since carotid denervation eliminates baroreceptor feedback and causes
      profound hypotension during hypoxia in anesthetized rats, potential contributions
      of these uncontrolled factors or residual chemoafferent neuron activity to
      residual pLTF cannot be ruled out. Since ATP is necessary for hypoxic carotid
      chemotransduction, we tested the hypothesis that functional peripheral
      chemoreceptor denervation (with intact baroreceptors) via systemic P2X receptor
      antagonism blocks hypoxic phrenic responses and AIH-induced pLTF in anesthetized
      rats. Pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 100 mg/kg
      i.v.), a non-selective P2X receptor antagonist, was administered to anesthetized,
      vagotomized, paralyzed and ventilated male Sprague-Dawley rats prior to AIH (3, 5
      min episodes of 10% O(2); 5 min intervals). Although PPADS strongly attenuated
      the short-term hypoxic phrenic response (20 +/- 4% vs. 113 +/- 15% baseline; P <
      0.001), pLTF was reduced but not eliminated 60 min post-AIH (25 +/- 4% vs. 51 +/-
      11% baseline; n = 8 and 7, respectively; P < 0.002). Thus, AIH initiates residual
      pLTF out of proportion to the diminished hypoxic phrenic response and
      chemoafferent neuron activation. Although the mechanism of residual pLTF
      following functional chemo-denervation remains unclear, possible mechanisms
      involving direct effects of hypoxia on the CNS are discussed.

PMID- 21093616
TI  - Ultrasound-guided percutaneous cryotherapy of hepatocellular carcinoma.
AB  - BACKGROUND: Reports on percutaneous cryoablation to treat patients with HCC are
      sparse in the medical literature. This study aimed to determine the safety and
      efficacy of percutaneous cryotherapy for unresectable or recurrent hepatocellular
      carcinoma (HCC). METHODS: The results of 40 patients with unresectable HCC and 26
      patients with recurrent HCC treated with ultrasound-guided percutaneous
      cryotherapy from January 2006 to June 2009 were retrospectively analyzed.
      RESULTS: We used percutaneous cryotherapy to treat 76 tumors in 40 patients with
      unresectable and 76 tumors in 26 patients with recurrent HCC. The size of the
      tumors was 2.8 +/- 1.7 cm (mean +/- S.D.). The mean number of treatment sessions
      for unresectable and recurrent HCC were 1.7 and 1.4, respectively. All
      cryotherapy procedures were technically successful. No procedure-related death
      was observed. The overall complication rate was 12.1%. Patients with unresectable
      HCC had 1-, and 3-year overall survival rates of 81.4%, and 60.3%, while the
      disease-free survival rates at 1 year and 3 years were 67.6% and 20.8%,
      respectively. Patients with recurrent HCC had 1-, and 3-year overall survival
      rates of 70.2%, and 28.8%, while the disease-free survival rates at 1 year and 3
      years were 53.8% and 7.7%, respectively. CONCLUSION: Ultrasound-guided
      percutaneous cryotherapy was safe and efficacious in the treatment of
      unresectable and recurrent HCC. Further randomized trials are needed to compare
      the safety and efficacy of cryotherapy with other forms of percutaneous treatment
      so that an unbiased therapeutic strategy can be devised.

PMID- 21093617
TI  - Limited pulmonary resection for peripheral small-sized adenocarcinoma of the
      lung.
AB  - BACKGROUND: It was recently reported that a limited pulmonary resection
      (segmentectomy or wedge resection) was not inferior to a lobectomy in the
      management of peripheral small-sized adenocarcinoma (tumor ? 20 mm) of the lung.
      METHODS: We retrospectively analyzed patients undergoing a lobectomy (n = 114)
      and a limited resection (n = 35) for peripheral small-sized adenocarcinoma of the
      lung during a 7-year period from April 2001 to March 2008. Our criteria for the
      limited resection of lung cancer were as follows: (1) adenocarcinoma of 10 mm or
      less in diameter and (2) adenocarcinoma of 11-20 mm in diameter, in which the
      ratio of the ground glass opacity is 50% or more, without pleural indentation on
      computed tomography. Additionally, the frozen sections of the tumors were
      intraoperatively diagnosed as Noguchi type A or B. The survival and clinical
      outcomes were analyzed. RESULTS: The 5-year survival rates of the lobectomy group
      and limited resection groups were 89.2% and 100%, respectively. No recurrence was
      seen in the limited resection group. CONCLUSIONS: Our results suggest that our
      criteria for limited resection were adequate for the management of small-sized
      adenocarcinoma of the lung.

PMID- 21093619
TI  - [How can we achieve even better results?].

PMID- 21093618
TI  - Characterization of statistically produced xylanase for enrichment of fruit juice
      clarification process.
AB  - Critical factors for xylanase production of Bacillus stearothermophilus under
      batch fermentation and for clarification of citrus fruit juice using this
      xylanase were optimized through central composite design of response surface
      methodology. Statistical approach resulted in an increase of 1.19-fold in
      xylanase yield over conventional method. Model equation for juice clarification
      included independent variables viz. temperature, incubation time and enzyme dose
      to study the dependent variables such as yield, acidic neutrality and
      filterability etc. Coefficient of determination, R(2) for enzyme production model
      and for different juice properties were in accordance with the linearity of the
      model. On the basis of the contour plots the optimum enzyme dose was 12.5 IU/g of
      xylanase. Enzymatic treatment has resulted in the improvement of twofold in the
      release of reducing sugars and 52.97% in juice yield, whereas 35.34% reduction in
      turbidity was observed.

PMID- 21093620
TI  - Preface: Oral disease.

PMID- 21093621
TI  - History and physical examination, screening and diagnostic testing.
AB  - The oral medicine specialist and oral pathologist are the disciplined
      subspecialists in dentistry who deal with oral disease and related systemic
      conditions. Dental colleagues are an invaluable resource for the diagnosis and
      treatment of diseases unfamiliar to the otolaryngologist. This article reviews
      the process of history taking, the physical examination, head and neck
      examination, oral soft tissue anatomy, the oral examination, and screening and
      diagnostic testing.

PMID- 21093622
TI  - Oral manifestations of smokeless tobacco use.
AB  - Smokeless tobacco (SLT) has been smoked, chewed, and inhaled in various forms for
      hundreds of years. The primary oral, mucosal, and hard tissue changes associated
      with SLT use include SLT keratosis (STK); gingival inflammation, periodontal
      inflammation, and alveolar bone damage; and dental caries, tooth abrasion, and
      dysplasia and oral squamous cell carcinoma (SCC). Some high-risk STKs are human
      papillomavirus associated, and the highest level of transition of STK to
      dysplasia or oral SCC appears to be in those lesions that have a diffuse velvety
      or papillary texture clinically. There is minimal risk for oral cancer associated
      with SLT use.

PMID- 21093623
TI  - Oral infections and antibiotic therapy.
AB  - Oral infections commonly originate from an odontogenic source in adults and from
      tonsil and lymphatic sources in children. Odontogenic infections arise from
      advanced dental caries or periodontal disease. Oral trauma, radiation injury,
      chemotherapy mucositis, salivary gland infection, lymph node abscess, and
      postoperative infection are potential nonodontogenic sources of infections that
      could potentially be life threatening. This article reviews the serious nature
      and potential danger that exists from oral infection and the antibiotics
      available to treat them are reviewed. Successful treatment requires an
      understanding of the microflora, the regional anatomy, the disease process, the
      treatment methods available, and interdisciplinary team collaboration.

PMID- 21093624
TI  - Recurrent aphthous stomatitis.
AB  - Recurrent aphthous stomatitis is a common oral ulcerative disease, affecting 10%
      to 15% of the general US population. This article reviews the epidemiology and
      clinical presentations of recurrent aphthous stomatitis, including diagnosis and
      management.

PMID- 21093625
TI  - Oral lichen planus.
AB  - Oral lichen planus (OLP) is a chronic, immune-mediated condition commonly
      affecting middle-aged women. The cause of OLP remains obscure. Strict clinical
      and histologic criteria need to be met to arrive at a definite diagnosis, thereby
      ruling out other conditions that may mimic OLP clinically and/or histologically.
      Although OLP is considered a premalignant condition, the risk for neoplastic
      change seems low.

PMID- 21093626
TI  - White lesions.
AB  - Increased thickness of the epithelium imparts a white appearance to the oral
      mucosa by increasing the distance to the underlying blood vessels. Usually this
      thickening is a result of the increased formation of keratin. Some other less
      common causes of white lesions are acanthosis or a thickening of the spinous cell
      layer, edema of the epithelium, or increased fibrosis of the connective tissue
      thereby reducing blood vessels. Occasionally the surface of an ulcer may appear
      white, due to collection of fibrin on the surface. In this article the authors
      discuss white lesions based on putative etiology, that is, hereditary, reactive,
      inflammation related, immunologic, traumatic, infection related, and idiopathic.

PMID- 21093627
TI  - Vesiculobullous eruptions of the oral cavity.
AB  - The spectrum of vesiculobullous eruptions of the oral cavity is wide and rich,
      with different disease entities that encompass different etiologies,
      pathogenesis, clinical manifestations, treatment plans, and prognostic ends.
      Trying to present all these entities in a comprehensive fashion is challenging,
      but in this article, most of the important entities pertaining to this topic have
      been encompassed in a concise manner.

PMID- 21093628
TI  - Common oral manifestations of systemic disease.
AB  - Oral manifestations of systemic diseases are potential indicators of an array of
      conditions. Truly the oral cavity is a mirror that reflects and unravels many of
      the human body's internal secrets. Some of these manifestations are disease
      specific and help raise a high degree of suspicion for the alert clinician.
      Because oral manifestations may accompany many systemic diseases, it is essential
      that these are appropriately recognized to provide correct diagnosis and referral
      for treatment and patient care. Multiple entities involving the various areas of
      the oral cavity like the soft palate, hard palate, tongue, gingiva, oral mucosa,
      the dentition, periodontium, and the salivary gland tissue have been enlisted.
      Although this article is not all-inclusive, the authors highlight lesions or
      conditions that are directly related to or are caused by some of the more common
      systemic diseases, and hope to provide ample insight for physicians, dentists,
      and clinicians in otolaryngologic practice.

PMID- 21093629
TI  - Oral manifestations of hematologic and nutritional diseases.
AB  - Oral manifestations of hematologic and nutritional deficiencies can affect the
      mucous membranes, teeth, periodontal tissues, salivary glands, and perioral skin.
      This article reviews common oral manifestations of hematologic conditions
      starting with disorders of the white blood cells including cyclic hematopoiesis
      (cyclic neutropenia), leukemias, lymphomas, plasma cell dyscrasias, and mast cell
      disorders; this is followed by a discussion of the impact of red blood cell
      disorders including anemias and less common red blood cell dyscrasias (sickle
      cell disease, hemochromatosis, and congenital erythropoietic porphyria) as well
      as thrombocytopenia. Several nutritional deficiencies exhibit oral
      manifestations. The authors specifically discuss the impact of water-soluble
      vitamins (B2, B3, B6, B9, B12, and C), fat-soluble vitamins (A, D, and K) and the
      eating disorders anorexia nervosa and bulimia nervosa on the oral mucosa.

PMID- 21093630
TI  - Burning mouth syndrome and secondary oral burning.
AB  - Burning mouth syndrome is a complex disorder of unclear etiology that is most
      prevalent in perimenopausal women. It is often accompanied by dysguesia and
      subjective xerostomia. Recent evidence implicates both central and peripheral
      neuropathies, possibly representing a phantom pain syndrome in some patients.
      Ensuring that the patient's oral burning is not secondary to some other local or
      systemic factor is central to appropriate management. Current standard therapies
      include clonazepam, paroxetine, and cognitive behavioral therapy, and several
      promising new alternatives are described.

PMID- 21093631
TI  - Early detection of premalignant lesions and oral cancer.
AB  - Cancers of the oral cavity account for approximately 3% of malignancies diagnosed
      annually in the United States. As with other upper aerodigestive tract cancers, 5
      year survival rates for oral cavity cancers decrease with delayed diagnosis.
      Cancers of the oral cavity are thought to progress from premalignant/precancerous
      lesions, beginning as hyperplastic tissue and developing into invasive squamous
      cell carcinoma. Despite the general accessibility of the oral cavity during
      physical examination, many malignancies are not diagnosed until late stages of
      disease. To prevent malignant transformation of these oral precursor lesions,
      multiple screening and detection techniques have been developed to address this
      problem.

PMID- 21093632
TI  - Diagnosis and management of oral candidiasis.
AB  - Oral candidiasis is the most common fungal infection in both the immunocompetent
      and the immunocompromised populations. This article reviews the clinical
      presentations of the different forms of oral candidiasis, as well as the
      diagnosis and management.

PMID- 21093633
TI  - Respect and care for the older person.

PMID- 21093634
TI  - Promoting women in science and medicine.

PMID- 21093635
TI  - Shortage of streptomycin: time for a change of approach?

PMID- 21093636
TI  - Measles eradication: past is prologue.

PMID- 21093637
TI  - Stronger national public health institutes for global health.

PMID- 21093638
TI  - Fast food feud at Golden Gate.

PMID- 21093640
TI  - CDC's Thomas Frieden--protecting health and reducing costs.

PMID- 21093641
TI  - Trastuzumab for gastric cancer treatment.

PMID- 21093643
TI  - Trastuzumab for gastric cancer treatment.

PMID- 21093645
TI  - Telemonitoring--or better follow-up?

PMID- 21093648
TI  - HDL cholesterol and residual risk of first cardiovascular events.

PMID- 21093649
TI  - Ethiopia struggles to make its voice heard.

PMID- 21093650
TI  - Missing centenarians in Japan: a new ageism.

PMID- 21093651
TI  - Facebook: a new trigger for asthma?

PMID- 21093652
TI  - Tired legs--a gut diagnosis.

PMID- 21093655
TI  - Use of a transparent dressing in the treatment of axillary hyperhidrosis with
      botulinum toxin type A.

PMID- 21093656
TI  - Nodular amyloidosis in a diabetic patient with frequent hypoglycemia: sequelae of
      repeatedly injecting insulin without site rotation.

PMID- 21093657
TI  - A case of indolent CD56-positive lymphomatoid papulosis.

PMID- 21093658
TI  - Pseudoscleroderma possibly induced by intravesical instillation of mitomycin C.

PMID- 21093659
TI  - The use of cyclosporine in dermatology: part I.
AB  - Cyclosporine is a calcineurin inhibitor that acts selectively on T cells. It has
      been used in dermatology since 1997 for its US Food and Drug Administration
      indication of psoriasis and off-label for various other inflammatory skin
      conditions, including atopic dermatitis, blistering disorders, and connective
      tissue diseases. In the last decade, many dermatologists have hesitated to use
      this important drug in their clinical practices because of its toxicity profile.
      The purpose of this article is to review the mechanism of action of cyclosporine
      and its current uses and dosing schedules. It is our goal to create a framework
      in which dermatologists feel comfortable and safe incorporating cyclosporine into
      their prescribing regimens. LEARNING OBJECTIVES: After completing this learning
      activity, participants should be able to describe the mechanism of action of
      cyclosporine, recognize the potential role of cyclosporine in dermatology and the
      evidence to support this role, and incorporate cyclosporine into his or her
      prescribing regimens.

PMID- 21093660
TI  - The use of cyclosporine in dermatology: part II.
AB  - Cyclosporine is highly effective in the treatment of a multitude of dermatoses.
      Concern over its side effect profile has limited its use in dermatology. Adverse
      effects are, for the most part, dose dependent and related to duration of
      therapy. Using the recommended monitoring protocols results in a significant
      decrease in the incidence of cyclosporine-related toxicities. This article
      provides a comprehensive review of the pharmacokinetics of cyclosporine,
      potential drug interactions, adverse effects, and recommendations for monitoring
      in patients treated with cyclosporine. The use of cyclosporine in pregnancy and
      in the pediatric population is also addressed. LEARNING OBJECTIVES: After
      completing this learning activity, participants should be familiar with the
      monitoring guidelines of cyclosporine, its contraindications, its possible drug
      interactions, its adverse effect profile, and its use in pregnancy and the
      childhood and adolescent populations.

PMID- 21093661
TI  - Gummy smile and botulinum toxin: a new approach based on the gingival exposure
      area.
AB  - BACKGROUND: Gummy smile (GS) is an aesthetic disorder for some patients, which
      can be corrected by injection of botulinum toxin. OBJECTIVE: We sought to
      classify GS according to the area of gingival exposure and the respective muscles
      involved in order to perfect the botulinum toxin injection technique for each
      patient. METHODS: Sixteen patients with GS were evaluated before receiving
      botulinum toxin injections. Based on the area of excessive gum displayed and
      identification of the muscles involved, 4 different types of GS were identified:
      anterior, posterior, mixed, and asymmetric. AbobotulinumtoxinA (Dysport, Ipsen
      Biopharm Limited, Wrexham, UK) was injected using a different injection technique
      for each type of GS, based on the main muscles involved. With the aid of two
      computer programs, the area of gum exposed was measured before and after the
      application of abobotulinumtoxinA, to evaluate the level of improvement. RESULTS:
      There was a decrease in the degree of gum display in all patients. The general
      average improvement achieved was 75.09%. Two patients showed slight adverse
      effects that were easily corrected with additional doses of abobotulinumtoxinA.
      LIMITATIONS: For this study, there was no sample size calculation and no
      statistical analysis of the cases. CONCLUSION: The authors conclude that it is
      important to identify the type of GS and therefore the main muscles involved, so
      that the correct injection technique can be used. AbobotulinumtoxinA was shown to
      be effective and safe for use in all types of GS in the present sample.

PMID- 21093662
TI  - Differentiation of vascular tumors from vascular malformations by expression of
      Wilms tumor 1 gene: evaluation of 126 cases.
AB  - BACKGROUND: Vascular tumors and malformations can be challenging to diagnose.
      Although they may initially appear very similar, they have distinct clinical
      courses and management. Wilms tumor 1 (WT1) gene expression has been reported in
      many different tumors including hematologic malignancies and some solid tumors.
      OBJECTIVE: We sought to evaluate the expression of WT1 in 126 vascular lesions
      (64 vascular tumors, one Masson tumor, and 61 vascular malformations). METHODS:
      Based on the International Society for the Study of Vascular Anomalies
      classification of vascular anomalies, we studied the expression of WT1 in
      vascular tumors composed of infantile hemangioma, congenital hemangiomas (non
      involuting, rapidly involuting, and not otherwise specified), pyogenic granuloma,
      tufted angioma, cherry angioma, Kaposi sarcoma, and angiosarcoma. We also studied
      WT1 expression in vascular malformations composed of angiokeratoma/verrucous
      hemangioma, combined vascular malformations, venous malformations, glomuvenous
      malformations, lymphatic malformations/lymphangioma, telangiectasia, and
      targetoid hemosiderotic hemangioma. RESULTS: All vascular tumors and
      proliferations had positive WT1 cytoplasmic endothelial immunostaining whereas
      only 3 vascular malformations were WT1 positive. Moreover the positivity of WT1
      in these vascular malformations was focal and involved only re-endothelialized
      neovessels within thrombi. LIMITATIONS: The low number of malignant vascular
      tumors is a limitation. CONCLUSIONS: Immunohistochemical detection of WT1 could
      be a useful tool to routine evaluation of vascular anomalies allowing the
      distinction of vascular tumors and proliferations from vascular malformations.
      Staining for WT1 may guide the clinician in difficult cases, as positive results
      would suggest a proliferative vascular lesion whereas negative results might
      point to a vascular malformation.

PMID- 21093663
TI  - Sixty-year-old man with slowly expanding nodular plaque on the thigh.

PMID- 21093664
TI  - Understanding over-the-counter medications and prescription devices for eczema:
      potential consequences for consumers.

PMID- 21093665
TI  - The Harvard program and the enduring legacy of Thomas B. Fitzpatrick.

PMID- 21093666
TI  - Comment on "Clinical genetic testing for familial melanoma in Italy: a
      cooperative study".

PMID- 21093667
TI  - Condyloma accuminata: what's in a name?

PMID- 21093668
TI  - Dermatology information on the Internet: an appraisal by dermatologists and
      dermatology residents.

PMID- 21093669
TI  - The clinical triage assistant: a new member of the dermatology health care team.

PMID- 21093670
TI  - Teledermatology: an examination of per-visit and long-term billing trends at East
      Carolina University from 1996 to 2007.

PMID- 21093672
TI  - Severe respiratory syncytial virus infection complicating treatment for infantile
      hemangioma.

PMID- 21093671
TI  - Prospective quality of life impact of keratinocyte carcinomas: observations from
      the Veterans Affairs Topical Tretinoin Chemoprevention Trial.

PMID- 21093673
TI  - Self-healing congenital generalized skin creases: Michelin tire baby syndrome.

PMID- 21093674
TI  - Morphea profunda in a young infant after hepatitis B vaccination.

PMID- 21093675
TI  - Preface: Traumatic brain injury: defining best practice.

PMID- 21093676
TI  - Emerging concepts in the pathophysiology of traumatic brain injury.
AB  - A complex set of molecular and functional reactions is set into motion by
      traumatic brain injury (TBI). New research that extends beyond pathological
      effects on neurons suggests a key role for the blood-brain barrier, neurovascular
      unit, arginine vasopressin, and neuroinflammation in the pathophysiology of TBI.
      The prevalence of molecular derangements in TBI holds promise for the
      identification and use of biomarkers to assess severity of injury, determine
      prognosis, and perhaps direct therapy. Hopefully, improved knowledge of these
      elements of pathophysiology will provide the mechanistic clues that lead to
      improved treatment of TBI.

PMID- 21093677
TI  - Blast-induced mild traumatic brain injury.
AB  - Traumatic brain injury (TBI) has been a major cause of mortality and morbidity in
      the wars in Iraq and Afghanistan. Blast exposure has been the most common cause
      of TBI, occurring through multiple mechanisms. What is less clear is whether the
      primary blast wave causes brain damage through mechanisms that are distinct from
      those common in civilian TBI and whether multiple exposures to low-level blast
      can lead to long-term sequelae. Complicating TBI in soldiers is the high
      prevalence of posttraumatic stress disorder. At present, the relationship is
      unclear. Resolution of these issues will affect both treatment strategies and
      strategies for the protection of troops in the field.

PMID- 21093678
TI  - Combat-related traumatic brain injury and its implications to military
      healthcare.
AB  - Traumatic brain injury (TBI) is a known injury in today's combat arena. Improved
      screening and surveillance methods have diagnosed TBI with increasing frequency.
      Current treatment plans are based largely on information gleaned from sports
      injuries. However, these management paradigms fail to address the effect of
      physiologic stress (fatigue, dehydration) and psychological stress at the time of
      injury as well as the number of previous concussions that may affect recovery
      from combat-related TBI. This article presents current evaluation and management
      of combat-related injury and discusses other psychological conditions that may
      coexist with TBI.

PMID- 21093679
TI  - Mild traumatic brain injury: key decisions in acute management.
AB  - The definition of a mild traumatic brain injury (TBI) has come under close
      scrutiny and is changing as a result of refined diagnostic testing. Although up
      to 15% of patients with a mild TBI will have an acute intracranial lesion
      identified on head computed tomography (CT), less than 1% of these patients will
      have a lesion requiring a neurosurgical intervention. Evidence-based guideline
      methodology has assisted in generating recommendations to facilitate clinical
      decision making; however, no set of guidelines is 100% sensitive and specific.
      Evidence supports the safety of discharging patients with mild TBI who have a
      negative CT. However, though patients with a negative CT are at almost no risk of
      deteriorating from a neurosurgical lesion, a key intervention is to provide these
      patients at discharge from the emergency department with counseling regarding
      postconcussive symptoms, when to return to work, school, or sports, and when to
      seek additional medical care.

PMID- 21093680
TI  - Traumatic brain injury and its neurobehavioral sequelae.
AB  - The neurobehavioral sequelae (NBS) of traumatic brain injury (TBI) consist of a
      spectrum of somatic, neurological, and psychiatric symptoms. The challenge for
      clinicians lies in understanding the interface of the various symptoms and how
      they interrelate with other entities. Specifically, the challenge is
      differentiating post-TBI-related symptoms from pre-existing or de novo
      psychiatric, neurological, and/or systemic disorders. A comprehensive evaluation
      and a multidisciplinary approach to evaluating patients are essential to be able
      to develop the differential diagnosis needed to design a management plan that
      maximizes recovery.

PMID- 21093681
TI  - Head computed tomography interpretation in trauma: a primer.
AB  - Noncontrast computed tomography (CT) provides important diagnostic information
      for patients with traumatic brain injury. A systematic approach to image
      interpretation optimizes detection of pathologic air, fractures, hemorrhagic
      lesions, brain parenchymal injury, and abnormal cerebrospinal fluid spaces. Bone
      and brain windows should be reviewed to enhance injury detection. Findings of
      midline shift and mass effect should be noted as well as findings of increased
      intracranial pressure such as hydrocephalus and cerebral edema, because these may
      immediately influence management. Compared with CT, magnetic resonance imaging
      may provide more sensitive detection of diffuse axonal injury but has no proven
      improvement in clinical outcomes. This article discusses key CT interpretation
      skills and reviews important traumatic brain injuries that can be discerned on
      head CT. It focuses on imaging findings that may deserve immediate surgical
      intervention. In addition, the article reviews the limits of noncontrast CT and
      discusses some advanced imaging modalities that may reveal subtle injury patterns
      not seen with CT scan.

PMID- 21093682
TI  - Neuropsychological assessment in traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a neurological injury that can affect the
      cognitive, emotional, psychological, and physical functioning of an individual.
      The clinical neuropsychologist working with TBI patients must take a holistic
      approach when assessing and treating the patient and consider the patient in
      total, including premorbid and post-incident factors, to formulate a
      comprehensive and accurate picture of the patient. This approach will guide the
      clinician regarding multiple types of treatment the patient may require.

PMID- 21093683
TI  - Rehabilitation of traumatic brain injury.
AB  - Rehabilitation following traumatic brain injury (TBI) is best provided by an
      interdisciplinary team of health care providers that takes advantage of the
      unique skills of multiple specialists, as well as their combined strengths that
      address problems that cut across disciplines. The setting where rehabilitation is
      provided is determined by the medical stability of patients, their ability to
      tolerate intensive therapies, and their likelihood of community reintegration
      within a reasonable period of time. Successful rehabilitation requires prompt
      recognition and treatment of TBI-related medical, cognitive, and behavioral
      problems to promote recovery and enhance community reintegration, using a
      combination of rehabilitation modalities and medications.

PMID- 21093684
TI  - Role and impact of cognitive rehabilitation.
AB  - Cognitive rehabilitation interventions are theoretically based and empirically
      validated treatments designed to ameliorate the cognitive, behavioral, and
      emotional impairments commonly experienced by individuals with traumatic brain
      injury (TBI). Cognitive rehabilitation can play many roles in facilitating
      recovery after TBI, such as improving impaired cognitive functions, increasing
      awareness of injury-related deficits, improving mood, facilitating vocational and
      community involvement, and reducing the probability of secondary disability. The
      considerable evidence documenting the impact of cognitive rehabilitation on
      improving the day-to-day function of individuals with TBI is described.

PMID- 21093685
TI  - Personalized medicine in traumatic brain injury.
AB  - Patients who have sustained a mild traumatic brain injury (TBI) from both
      civilian and military populations exhibit clinical symptoms of varying severity
      with minimal to profound impact on their daily functioning. Although most
      patients make a full recovery, a subgroup of mild TBI patients develop cognitive,
      somatic, and neurobehavioral sequelae that generally resolve over 3 to 6 months;
      a smaller subgroup develop persisting symptoms. The reason why a mild TBI results
      in varying clinical symptoms is currently unknown. Based on evidence that
      microRNA species in peripheral blood mononuclear cells (PBMCs) may reflect
      molecular alterations in neurodegenerative disorders, it can be hypothesized that
      at early, preclinical phases of the disease, PBMC may provide an ideal and
      clinically assessable "window" into the brain. Thus, it is conceivable that
      changes in the expression profile of clinically accessible biological indices
      (biomarkers), such as microRNA in PBMC, may reflect molecular alterations
      following TBI that contribute to the onset and progression of TBI phenotypes
      including chronic traumatic encephalopathy. It is possible that the availability
      of TBI biomarkers may provide potential elements with clinical relevance to
      prevention, prognosis, and treatment of postconcussive disorders.

PMID- 21093686
TI  - Current issues in neurolaw.
AB  - Traumatic brain injury has received significant attention in recent years.
      Advances in diagnosis and management have resulted in opportunities to improve
      patient outcomes; however, controversies in diagnosis and management have
      resulted in increased interactions between the medical and legal communities.
      This article highlights some of the areas of controversy in traumatic brain
      injury litigation with the hope that synchronous resolutions of both legal and
      medical issues will ultimately benefit patient care. It is imperative that the
      neuroscience community engage the legal community to facilitate an understanding
      of the issues and their ramifications. Proactive communication and understanding
      between medical and legal specialties offer the potential to maximize
      efficiencies in our health care and legal systems.

PMID- 21093687
TI  - Risk factors for laboratory-confirmed household transmission of pandemic H1N1
      2009 infection.
AB  - Household transmission of the pandemic H1N1 2009 virus infection (pH1N1)
      frequently occurred in children and adolescents within several days after
      development of index cases. However, antiviral therapy for index cases did not
      seem to prevent household transmission of pH1N1.

PMID- 21093688
TI  - 30 years later: reflections from AJIC's first editor, 1978-1995.

PMID- 21093689
TI  - The journal's past.

PMID- 21093690
TI  - The present.

PMID- 21093691
TI  - The future of AJIC.

PMID- 21093692
TI  - Editorial. A hope fulfilled.

PMID- 21093693
TI  - Report from APIC 2010.

PMID- 21093695
TI  - Expanding infection preventionists' influence in the 21st Century: looking back
      to move forward.
AB  - The 5th Decennial International Conference on Healthcare-Associated Infections
      took place in Atlanta in March 2010. The conference was unprecedented in the
      variety, depth, and breath of scientific sessions and research abstracts
      informing the practice of health care epidemiology and infection prevention.
      However, noticeably absent were topics or related discussions focused on
      essential leadership skills and influence strategies required to implement the
      science into practice.

PMID- 21093694
TI  - Moving evidence from the literature to the bedside: report from the APIC Research
      Task Force.
AB  - Research is an integral component of the mission of the Association for
      Professionals in Infection Control and Epidemiology (APIC). In January 2010, APIC
      's Board of Directors decided to update and clarify the Association's approach to
      research. The purpose of this paper is to briefly review the history of APIC's
      role in research and to report on the recent vision and direction developed by a
      research task force regarding appropriate roles and contributions for APIC and
      its members in regards to research. APIC and its membership play critical roles
      in the research process, especially in terms of setting the research agenda so
      that research resources can be directed to important areas. Additionally,
      dissemination and implementation are areas in which APIC members can utilize
      their unique talents to ensure that patients receive the most up-to-date and
      evidence-based infection prevention practices possible.

PMID- 21093696
TI  - Injection practices among clinicians in United States health care settings.
AB  - BACKGROUND: Improper use of syringes, needles, and medication vials has resulted
      in patient-to-patient transmission of bloodborne pathogens, including hepatitis C
      virus. This study examined the injection practices of health care providers to
      identify trends and target opportunities for education on safe practices.
      METHODS: An on-line survey was conducted in May and June 2010 of clinicians in US
      health care settings that prepare and/or administer parenteral medications.
      RESULTS: The majority of the 5446 eligible respondents reported injection
      practices consistent with current recommendations. However, the following unsafe
      practices were identified: 6.0% "sometimes or always" use single-dose/single-use
      vials for more than 1 patient; 0.9% "sometimes or always" reuse a syringe but
      change the needle for use on a second patient; 15.1% reuse a syringe to enter a
      multidose vial and then 6.5% save that vial for use on another patient (1.1%
      overall). CONCLUSION: Unsafe injection practices represent an ongoing threat to
      patient safety. Ensuring safe injection practices in all health care settings
      will require a multifaceted approach that focuses on surveillance, oversight,
      enforcement, and continuing education.

PMID- 21093697
TI  - Sharps injury reduction using a sharps container with enhanced engineering: a 28
      hospital nonrandomized intervention and cohort study.
AB  - BACKGROUND: The decrease in reported sharps injuries (SI) in the United States
      has markedly slowed. Additional devices and strategies need investigation. Sharps
      containers are associated with SI, and more than 90% of these injuries are
      related to container design. This study addresses the hypothesis that containers
      with enhanced engineering can reduce SI. METHODS: In a before/after intervention
      study from 2006 to 2008, we examined the impact of conversion to a sharps
      container with enhanced engineering (the Device) on SI categories in 14 Ascension
      Health hospitals (study group). The Device's safety features included large
      horizontal aperture, sensitive counterbalanced door, large atrium, and passive
      overfill prevention. Study group results were also compared with a control cohort
      of 14 contemporaneous size-matched, Ascension Health hospitals (control group).
      RESULTS: The Device was associated with significant reductions in after-procedure
      (-30%), disposal-related (-57%), and container-associated (-81%) SI in the study
      group. No significant reductions occurred in container-associated sharps injuries
      in the control group. Hospitals using the Device had significantly fewer total SI
      than control hospitals. CONCLUSION: Enhanced aperture design can significantly
      reduce container-associated sharps injuries. Other factors contributing to
      reduced injuries may include 1-hand deposit, safe closure, hand restriction, and
      preassembly. These results, from a country where sharps safety devices are
      widespread, are particularly applicable to countries where safety devices are not
      extensively used.

PMID- 21093698
TI  - Daily chlorohexidine gluconate bathing with impregnated cloths results in
      statistically significant reduction in central line-associated bloodstream
      infections.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSI) contribute to
      increased morbidity, mortality, length of stay, and excessive cost of care.
      METHODS: This study was an observational cohort study using historical controls
      in the setting of a 9-bed surgical intensive care unit in a Level I trauma
      center; all patients admitted or transferred into the unit were enrolled in the
      study. OBJECTIVES: A quality improvement intervention protocol was instituted to
      reduce CLABSI incidence with a 3-month effectiveness study using 2% chlorhexidine
      gluconate-impregnated cloths for daily patient bathing; education of surgical
      intensive care unit staff on changes to CLABSI prevention protocol and all
      existing CLABSI prevention policies and bundles already in place; and compliance
      monitoring and documentation. RESULTS: The 3-month effectiveness study showed a
      decrease in CLABSI rates from 12.07 CLABSIs per 1000 central line-days to 3.17
      CLABSIs per 1000 central line-days (73.7% rate reduction; P = .0358). CONCLUSION:
      CLABSI incidence rates were reduced in a high-risk patient population using
      evidence-based prevention bundles and implementing daily bathing with 2%
      chlorhexidine gluconate nonrinse cloths.

PMID- 21093699
TI  - Validation of the surveillance and reporting of central line-associated
      bloodstream infection data to a state health department.
AB  - BACKGROUND: The primary goal of health care-associated infection reporting is to
      identify and measure progress towards achieving the irreducible minimum number of
      infections. Assessing the accuracy of reporting data using independent validation
      is critical to this goal. In January 2008, all 30 acute care hospitals in
      Connecticut began mandatory reporting of central line-associated bloodstream
      infections (CLABSI) to the National Healthcare Safety Network (NHSN) system.
      METHODS: A state nurse epidemiologist performed a blinded retrospective chart
      review for NHSN-reported CLABSI based on positive blood cultures from October to
      December 2008. RESULTS: Of 476 septic events, 48 met the NHSN CLABSI definition,
      of which 23 (48%) had been reported to NHSN. Concordance of non-CLABSI events was
      99% sensitive. Components of the case definition that were a source of
      misinterpretation included the following: NHSN surveillance definition of primary
      and secondary bacteremia (45%), CLABSI rules (19%), CLABSI terms (10%), and
      differentiation between laboratory-confirmed bloodstream criterion 1 (recognized
      pathogen) and criterion 2 (skin contaminant) (13%). CONCLUSION: The validation
      study identified >50% underreporting of CLABSI, most related to misinterpretation
      of components of the NHSN definition. Continued validation and training will be
      needed in Connecticut to improve completeness of reported health care-associated
      infection data and to assure that publicly reported data are valid.

PMID- 21093700
TI  - [The "peer-review" process in biomedical journals: characteristics of "Elite"
      reviewers].
AB  - The "peer-review" system is used to improve the quality of submitted scientific
      papers and provides invaluable help to the Editors in their decision-making
      process. The "peer-review" system remains the cornerstone of the scientific
      process and, therefore, its quality should be closely monitored. The profile of
      the "elite" reviewers has been described, but further studies are warranted to
      better identify their main characteristics. A major challenge, not only for
      Editors but also for medical scientific societies as a whole, is to continue to
      guarantee the excellence in the "peer-review" process and to ensure that it
      receives adequate academic recognition.

PMID- 21093701
TI  - [The profile of evaluators of a medical publication in relation to the response].
AB  - INTRODUCTION: The expert is essential in the external evaluation process and for
      this reason it is necessary to know the profile and characteristics of the best
      evaluators. MATERIAL AND METHODS: We have retrospectively analysed the external
      review process of the journal from the 1st of January 2005 until the 30th of June
      2009, with the aim of knowing the profile of the experts in relation to the
      response to the requests. The response rate, mean delay time and responder rate
      were evaluated, using, sex, age and forming part of the editorial committee as
      variables. RESULTS: The response rate fell as the number of evaluations
      increased. Women had a higher response rate, lower delay time and better
      performance than males. The response rate showed a tendency to decrease with age
      and the large majority of responders were between 29 and 39 years. Being a member
      of the journal committees was not associated with a better response rate,
      although there was less delay. The response rate and the delay time are similar,
      although it may increase with the number of requests to a reviewer. CONCLUSIONS:
      Lower age and being female are associated with a better response. No fatigue
      effect was observed in good responders, but if there is a fall in the response
      rates the number of evaluators should be increased.

PMID- 21093703
TI  - [Proposals to improve adherence to immunomodulatory therapies in patients with
      multiple sclerosis].
AB  - INTRODUCTION: The objective of this work was to assess the factors identified in
      the Global Adherence Project (GAP) in disease-modifying therapy (DMT) in patients
      with multiple sclerosis (MS) and to propose measures directed at improving
      adherence. It was proposed to prepare questionnaires to detect patients at risk
      of non-adherence before and during the follow-up. METHODS: Two meetings were held
      by Spanish researchers involved in the GAP project. Factors associated with non
      adherence were grouped in therapy-, patient-, disease- and health care
      professional-related factors. Four working groups were created. Each group
      studied one individual,factor, taking into account the stages of diagnosis,
      management and administering treatment, follow-up and discontinuation or change
      of treatment. A draft of proposals and tools (questionnaires) was agreed.
      RESULTS: Patients should be provided with summaries of treatments, in a positive
      and simple way, and have time to discuss any doubts. Questionnaires should be
      given to patients at the start of treatment and during follow-up, so that
      individual characteristics can be assessed in order to monitor their adherence
      and act accordingly. Patients should be instructed in the management of the most
      common adverse reactions. CONCLUSION: Therapeutic education to improve adherence
      to treatments and identification of non-adherent patients is recommended. We
      propose 2 questionnaires, initial and follow up, to stratify patients depending
      on their adherence.

PMID- 21093702
TI  - [Experience with continuous levodopa enteral infusion (Duodopa((r))) in patients
      with advanced Parkinson's disease in a secondary level hospital].
AB  - INTRODUCTION: Continuous levodopa delivery by enteral infusion (Duodopa((r))) is
      an alternative to deep brain stimulation and subcutaneous apomorphine to control
      motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We
      report our experience with Duodopa((r)) therapy in 11 patients with advanced PD.
      METHODS: We retrospectively assessed clinical and quality of life changes in all
      patients with PD with severe motor fluctuations and dyskinesias who started
      continuous daily levodopa duodenal infusion through percutaneous endoscopic
      gastrostomy from September 2006 (Duodopa((r)) was approved for advanced PD
      treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of
      Spain. RESULTS: Nine patients received Duodopa((r)) [62.7+/-10.6 (44-74) years,
      63.6% male)]. Pre-Duodopa((r)) clinical characteristics of patients were: disease
      duration 14.5+/-8.9 (3-34) years, oral levodopa dose 918.2+/-277.7 (450-1300)
      mg/day, and Hoehn and Yahr staging 3.7+/-0.5 (3-4). Nine patients are still
      receiving Duodopa((r)). Patients improved motor fluctuations (72.7% significant
      improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%)
      and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months
      (3-31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39
      (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5+/-19.8 and
      24+/-12.5 respectively (P<0.05). Equivalent daily dose of levodopa (April 2010)
      was 1683.4+/-295.8 (1234-2216) mg/day. CONCLUSIONS: Intraduodenal infusion of
      levodopa offers an important alternative in treating patients with advanced
      Parkinson disease.

PMID- 21093704
TI  - [Bacterial meningitis secondary to spinal analgesia and anaesthesia].
AB  - INTRODUCTION: Although rare, infectious complications from spinal analgesia and
      anaesthesia (SA) can have serious morbidity and mortality. This study describes
      the clinical features and outcome of SA-associated bacterial meningitis in adults
      seen in a hospital over a 25 yearperiod. METHODS: We reviewed the charts of all
      patients (aged >=14 years) diagnosed with SA-associated bacterial meningitis
      between 1982 and 2006. RESULTS: Eight cases of SA-associated bacterial meningitis
      were diagnosed (3.3% bacterial meningitis), with a median age of 62 years (range,
      35-80). SA procedures were: morphine infusion pumps with epidural (3 cases) or
      intrathecal (3) catheters, spinal cord stimulation with epidural neuroelectrode
      (1), and epidural anesthesia (1). Site of spinal insertion was: cervical (2
      cases), thoracic (3), and lumbar (3). The median time to onset of meningitis was
      26 days (range, 7-101) after AE. The most common clinical findings were fever (8
      cases, 100%), headache (7 cases, 87.5%), and neck stiffness (4 cases, 50%). CSF
      abnormalities were pleocytosis (8 cases, 100%), elevated protein level (8 cases,
      100%), and hypoglycorrhachia (5 cases, 62.5%). The causative organisms were
      Staphylococcus epidermidis (2 cases), Staphylococcus aureus (2), Enterococcus
      faecalis (1), Streptococcus milleri (1), and S. epidermidis and Pseudomonas
      fluorescens (1); one patient had a negative CSF culture. Treatment included
      antibiotics and to remove the analgesia device in all patients. There was one
      death (12.5%). CONCLUSIONS: SA is a rare predisposing condition to bacterial
      meningitis but, due to the seriousness of the infection, it should be considered
      in the differential diagnosis for any patient who develops fever or headache in
      this setting.

PMID- 21093705
TI  - [Specific neurology emergency training of medical residents in Spain].
AB  - INTRODUCTION: Training in emergency neurological illness is very important for
      the neurologist today. The Neurology National Commission has decided to obtain
      information on the work duties of neurologist residents in the different
      neurology units of the hospitals of our country and the supervision of the
      training in urgent pathology. METHOD: A survey of adult neurology program
      directors to find out if their hospital fulfils the program criteria for the
      residents duty work. RESULTS: A response rate of 98.5% was obtained. In 47% of
      the neurology training units a neurologist supervised resident duty work 24 hours
      a day. In the rest of the neurology training units they did not fulfil all the
      training program criteria. We analysed the differences between the neurologist
      training units, and there are great differences between the hospitals and all
      regions and communities in our country. Only 65% of neurology residents do their
      education in neurology units who fulfill the national program criteria on
      training on urgent neurology pathology CONCLUSIONS: There is too much diversity
      in resident duty work in neurologist training units and not all the units meet
      the national training program requirements.

PMID- 21093707
TI  - [Reversible posterior leucoencephalopathy in a patient with spinal cord injury].

PMID- 21093706
TI  - [Neurobiology and neurogenetics of dyslexia].
AB  - INTRODUCTION: Dyslexia is a learning disability in which reading (but not any
      other) impairment is the most prominent symptom. There seems to be a high
      comorbidity among dyslexia and other learning disabilities, such as SLI, SSD or
      ADHD. DEVELOPMENT: The nulear deficit in dyslexia appears to correspond to an
      impairment in phonological processing. Structural and functional studies in
      dyslexic readers converge to indicate the presence of malformations in the brain
      areas corresponding to the reading systems, but also a failure of these systems
      to function properly during reading. Genes linked (or associated) to dyslexia
      have been shown to be involved in neuronal migration and axon guidance during the
      formation of the cortex. In the developing cerebral neocortex of rats, local loss
      of function of most of these genes not only results in abnormal neuronal
      migration and neocortical and hippocampal malformations, but also in deficits
      related to auditory processing and learning. While the structural malformations
      resemble neuronal migration abnormalities observed in the brains of individuals
      with developmental dyslexia, processing/learning deficits also resemble deficits
      described in individuals affected by the disease. CONCLUSIONS: On the whole,
      dyslexia seems to be on a continuum with typical reading at different biological
      levels (genetic, biochemical, physiological, cognitive). Furthermore, certain
      elements belonging to some of these levels (mainly -some of the- genes linked or
      associated to the disease, but also -some of the- neuronal structures whose
      development is regulated by these genes) would simultaneously belong to those of
      other cognitive abilities, which give rise to diseases of a different nature
      (i.e. non- dyslexic impairments) when they are impaired.

PMID- 21093708
TI  - [Convulsive status epilepticus associated with a tramadol overdose].

PMID- 21093709
TI  - [Autoimmune vestibulopathy associated with autoreactive antibodies and parotid
      involvement].

PMID- 21093710
TI  - [Caudal nucleus haemorrhage due to dental anaesthesia].

PMID- 21093711
TI  - [The cell cycle and gene p53. An approach to molecular ophthalmology].

PMID- 21093712
TI  - [The non-mydriatic camera as a screening method in diabetics in Tarragona].
AB  - OBJECTIVE: The aim of the study is to present the results of the first year of
      using a non-mydriatic fundus camera. We performed an evaluation of its usefulness
      and problems. METHODS: During the first year of using the non-mydriatic fundus
      camera we evaluated 3,272 type II diabetic patients who were not being controlled
      in the hospital. RESULTS: The diabetic retinopathy was observed in 164 patients
      (5.01%), the mild form in 70 patients (2.14%). Diabetic macular oedema was
      observed in 41 patients (1.25%). In 119 patients (3.63%) the retinography could
      not be interpreted and were referred to the hospital; 113 patients also were
      referred due to other pathologies; the largest group of these patients had age
      related macular disease or age-related macular degeneration (42 patients).
      Finally, 458 patients (13.99%) required mydriatic eye-drops. CONCLUSIONS: The non
      mydriatic fundus camera is a useful technique for assessing the presence of
      diabetic retinopathy, particularly in patients with poor ophthalmic control. This
      technique may enable us to diagnose these patients who need laser treatment.

PMID- 21093713
TI  - [Clinical- histological correlation in patients with dry eye].
AB  - AIM: It is well known that there is a lack of association between symptoms and
      signs in patients with dry eye disease. The purpose of this study was to assess
      if there was any agreement between common dry eye diagnostic tests and to compare
      them with impression cytology. METHODS: A total of 40 patients were enrolled in
      this cases-controls study. The group of cases consisted of 20 patients previously
      diagnosed with dry eye and the controls were 20 volunteers. The examination
      included: the quality of life test OSDI, break up time test (BUT), fluorescein
      staining, Schirmer's test and finally the study of goblet and conjunctival
      epithelial cells with impression cytology. The Student t and U Mann-Whitney tests
      were used to evaluate the results, and Spearmans Rho coefficient to assess their
      correlation. RESULTS: Statistical differences were observed between cases and
      controls Group for all tests (P<0.0001). After assessing the good correlation
      between BUT, fluorescein staining and Schirmer's test, we studied their
      association with the impression cytology. The number of isolated goblet cells
      showed a weak association with the majority of tests, however the grade of
      metaplasia showed a greater association. CONCLUSION: Impression cytology is a
      valuable test in the diagnosis of dry eye. Although the number of goblet cells is
      not a sufficient diagnostic criterion, its joint assessment with the grade of
      metaplasia and the other dry eye tests is useful.

PMID- 21093714
TI  - [Macular oedema due to rosiglitazone treatment in diabetes mellitus].
AB  - CASE REPORT: A 61-year-old woman with type 2 diabetes mellitus for 7 years for
      which she was prescribed insulin therapy. Rosiglitazone (4 mg once daily) was
      introduced with adequate blood glucose control. One month later, she presented
      with complaints of systemic oedema and loss of vision. Fundoscopy showed
      bilateral macular oedema. A systemic study demonstrated peripheral oedema.
      Rosiglitazone was stopped and she was managed conservatively with a rapid
      resolution of the oedemas and at fundus examination there was no decrease in the
      macular oedema. DISCUSSION: This case reminds us of the importance of identifying
      potential toxicities of glitazone regimens. Glitazone use appears to be a cause
      of macular oedema, and stopping the drug may not resolve this oedema.

PMID- 21093715
TI  - [The vaporiser of Dr. Lourenco. Eye hydrotherapy in the XIX century].

PMID- 21093716
TI  - [The occluded eye of the princess of Eboli].

PMID- 21093717
TI  - Frailty. Preface.

PMID- 21093718
TI  - The frailty syndrome: definition and natural history.
AB  - This article reviews the current state of knowledge regarding the epidemiology of
      frailty by focusing on 6 specific areas: (1) clinical definitions of frailty, (2)
      evidence of frailty as a medical syndrome, (3) prevalence and incidence of
      frailty by age, gender, race, and ethnicity, (4) transitions between discrete
      frailty states, (5) natural history of manifestations of frailty criteria, and
      (6) behavior modifications as precursors to the development of clinical frailty.

PMID- 21093719
TI  - Frailty defined by deficit accumulation and geriatric medicine defined by
      frailty.
AB  - As nonreplicative cells age, they commonly accumulate subcellular deficits that
      can compromise function. As people age, they too experience problems that can
      accumulate. As deficits (symptoms, signs, illnesses, disabilities) accumulate,
      people become more susceptible to adverse health outcomes, including worse health
      and even death. This state of increased risk of adverse health outcomes is
      indistinguishable from the idea of frailty, so deficit accumulation represents
      another way to define frailty. Counting deficits not only allows grades of
      frailty to be discerned but also provides insights into the complex problems of
      older adults. This process is potentially useful to geriatricians who need to be
      experts in managing complexity. A key to managing complexity is through
      instruments such as a comprehensive geriatric assessment, which can serve as the
      basis for routine clinical estimation of an individual's degree of frailty.
      Understanding people and their needs as deficits accumulate is an exciting
      challenge for clinical research on frailty and its management by geriatricians.

PMID- 21093720
TI  - The biology of aging and frailty.
AB  - In developing and validating the concept of frailty as a geriatric syndrome, it
      has been necessary to distinguish the clinical expression of frailty from normal
      age-related changes and other age-related disease pathologies. A framework for
      excluding potentially confounding disease and a working clinical tool to diagnose
      frailty have been provided. The associations between frailty and other
      pathophysiologies has also been shown. However, investigating the underlying
      biologic basis for the geriatric syndrome of frailty by studying basic
      homeostatic pathways and mechanisms has not proceeded at the same rate. The
      following article provides an overview of the homeostatic pathways emphasized in
      research on aging and explains how this science may help to stimulate frailty
      research.

PMID- 21093721
TI  - Frailty and chronic diseases in older adults.
AB  - There are two hallmarks of aging that must be considered primary concerns when
      trying to improve health for older adults: frailty and chronic diseases. Some
      pathologic mechanisms related to diseases may help to explain frailty. This
      article describes known associations among frailty and chronic diseases and
      introduces punished inefficiency as an explanatory framework for frailty.
      Punished inefficiency proposes that having several physiologic impairments leads
      to physiologic inefficiencies. These inefficiencies may become manifest as
      frailty, often in the presence of disease. Therefore, frail older adults perform
      less external work because they must spend more on an absolute scale out of a
      smaller pool of internal resources. Stress imposed on frail older adults
      strengthens this negative feedback to activity, leading to disuse. This article
      discusses how people with frailty and chronic diseases may experience a malignant
      course and thereby intends to improve the ability to identify beneficial biologic
      and health care delivery strategies for older adults with, or at risk of,
      frailty.

PMID- 21093722
TI  - The frail renin-angiotensin system.
AB  - Over the last few decades, the understanding of the renin-angiotensin system
      (RAS) has advanced dramatically. RAS is now thought to play a crucial role in
      physiologic and pathophysiologic mechanisms in almost every organ system and is a
      key regulator of hypertension, cardiovascular disease, and renal function.
      Angiotensin II (Ang II) promotes inflammation and the generation of reactive
      oxygen species and governs onset and progression of vascular senescence, which
      are all associated with functional and structural changes, contributing to age
      related diseases. Although the vast majority of the actions of Ang II, including
      vascular senescence, are mediated by the Ang II type 1 receptor (AT1R), the
      identification, characterization, and cloning of the angiotensin type 2 receptor
      has focused attention on this receptor and to its antagonistic effect on the
      detrimental effects of AT1R. This review provides an overview of the changes in
      RAS with aging and age-disease interactions culminating in the development of
      frailty.

PMID- 21093724
TI  - Inflammation and immune system alterations in frailty.
AB  - Frailty is an important geriatric syndrome characterized by multisystem
      dysregulation. Substantial evidence suggests heightened inflammatory state and
      significant immune system alterations in frailty. A heightened inflammatory state
      is marked by increases in levels of inflammatory molecules (interleukin 6 and C
      reactive protein) and counts of white blood cell and its subpopulations, which
      may play an important role in the pathogenesis of frailty, directly or through
      its detrimental influence on other physiologic systems. Alterations in the innate
      immune system include decreased proliferation of the peripheral blood mononuclear
      cells and upregulated monocytic expression of specific stress-responsive
      inflammatory pathway genes. In the adaptive immune system, although little
      information is available about potential B-cell changes, significant alterations
      have been identified in the T-cell compartment, including increased counts of
      CD8+, CD8+CD28-, CCR5+T cells, above and beyond age-related senescent immune
      remodeling.

PMID- 21093725
TI  - The clinical care of frail, older adults.
AB  - Frailty and its management represent an emerging area of clinical care in older
      adults. Geriatricians have long recognized a syndrome of multiple comorbid
      conditions, immobility, weakness, and poor tolerance of physiologic stressors in
      older adults. Patients with these characteristics are described as frail and
      suffer increased adverse clinical outcomes. This article reviews the clinical
      spectrum of frailty in older adults, its biologic etiology, and potential
      clinical interventions. Several operational definitions of frailty and the
      associated clinical signs, symptoms, and outcomes are outlined. The biologic
      mechanisms hypothesized to underlie frailty are explored, particularly in the
      musculoskeletal, endocrine, and immune systems. Treatment options for frail,
      older adults are discussed, including physiologic system-targeted interventions
      and geriatric models of care.

PMID- 21093723
TI  - Anemia in frailty.
AB  - Although anemia is regarded as a relatively common occurrence in older adults,
      the vigor with which the medical community should intervene to correct this
      common problem is disputed. Epidemiologic data clearly correlate anemia with
      functional decline, disability, and mortality. Anemia may contribute to
      functional decline by restricting oxygen delivery to muscle, or to cognitive
      decline by restricting oxygen delivery to the brain. On the other hand, the
      erythron may be a separate target of the same biologic mediators that influence
      deterioration of physiologic systems that contribute to weakness, functional and
      cognitive decline, and mortality. Clinical trials aimed at treating anemia in
      older adults could assess whether physical performance is improved or whether
      mortality risk declines with improved hemoglobin, but sufficient evidence from
      such trials is currently lacking. With few guidelines regarding treatment of
      older adults and significant risk for adverse events associated with transfusion
      and erythroid stimulating agents, anemia often goes untreated or ignored in
      geriatric clinics. This article reviews the problem of anemia in older adults,
      with a particular emphasis on the frail elderly. The gaps in the evidence base
      for the treatment of anemia in older adults are reviewed and the options for
      advancing the field are assessed.

PMID- 21093726
TI  - Exercise as an intervention for frailty.
AB  - By 2015, nearly 15% of the US population will be older than 65 years. In 2030,
      there will be more than 70 million older Americans. This increase in the elderly
      population has prompted interest in recent years toward the study of frail older
      adults. This article reviews the literature investigating the utility of aerobic
      and resistance exercise training as an intervention for frailty in older adults.
      In addition, areas of future research are addressed, including concerns related
      to the dissemination of exercise interventions on a widespread scale. Guidelines
      for an "exercise prescription" for frail older adults are briefly outlined.

PMID- 21093727
TI  - Idiopathic intracranial hypertension in children: a review and algorithm.
AB  - This updated review of pediatric idiopathic intracranial hypertension focuses on
      epidemiology, clinical presentations, diagnostic criteria, evaluation, clinical
      course, and treatment. General guidelines for the clinical management of
      idiopathic intracranial hypertension are discussed. A new algorithm outlines an
      efficient management strategy for the initial diagnostic evaluation of children
      with signs or symptoms of intracranial hypertension. This algorithm provides a
      systematic approach to initial evaluation and management, and identifies
      important decision-making factors. The risk of permanent visual loss with
      idiopathic intracranial hypertension necessitates a prompt, thorough
      collaborative approach in the management of patients. Although idiopathic
      intracranial hypertension has been recognized for over a century, the need
      remains for prospectively collected data to promote a better understanding of the
      etiology, risk factors, evaluative methods, and effective treatments for children
      with this syndrome.

PMID- 21093728
TI  - Microarray analysis in children with developmental disorder or epilepsy.
AB  - The technique of chromosomal microarray analysis identifies genetic imbalance.
      Evaluation of its diagnostic role in pediatrics is still underway. We describe
      our experience with chromosomal microarrays. We retrospectively reviewed the
      charts of children in the Sections of Neurology and Clinical Genetics at St.
      Christopher's Hospital for Children who had undergone microarray analysis between
      2006 and 2009. Collected data included age, sex, and the presence of mental
      retardation, developmental delay, autism, learning disability, hypotonia,
      dysmorphic features, and epilepsy, and the use of microarray technique.
      Statistical analysis was performed using SPSS. There were 82 children (mean age
      +/- S.D., 5.7 +/- 5 years), including 45 (55%) boys and 37 (45%) girls. All
      patients exhibited a normal karyotype. Microarray analysis produced abnormal
      results in 20 (23.5%). Deletions comprised 74% of all abnormalities. Patients
      with >= 4 clinical variables demonstrated a 30.5% incidence of abnormal
      chromosomal microarray findings, compared with 8.7% of patients with <= 3
      clinical variables (P = 0.039, chi(2) test). Logistic regression indicated that
      motor impairment (P = 0.039) and presence of epilepsy (P = 0.024) independently
      contributed to the model. The likelihood of an abnormal microarray result
      increased with the number of clinical abnormalities. Microarray analysis will
      likely become the diagnostic genetic test of choice in children with
      neurodevelopmental disorders or epilepsy.

PMID- 21093729
TI  - Dysembryoplastic neuroepithelial tumors: a prospective clinicopathologic and
      outcome study of 13 children.
AB  - Dysembryoplastic neuroepithelial tumors (DNETs) are benign intracortical masses
      that are typically observed in children and young adults and are classified as
      glioneuronal tumors (WHO grade I). Large and retrospective series of patients
      with DNETs have been reported, but prospective studies on pediatric cohorts of
      patients with DNETs have been lacking. In the present study, 13 children (8 boys,
      5 girls; age 8-18 years) who had simple (n = 2) or complex (n = 11) partial
      seizures (seizure duration range, 2-4 years; mean, 1.5 years; mode, 1.2 years)
      were prospectively enrolled and monitored over 13 years. The DNETs were located
      in the frontal (n = 2), temporal (n = 9), or occipital (n = 2) cortex. In 11/13
      cases, the seizures were resistant to drug therapy, and all the children had
      surgery consisting of extended lesionectomy coupled with neuronavigation.
      Pathology examination revealed cortical dysplasia (n = 8), glial nodules (n =
      11), calcification (n = 4), cellular atypia (n = 3), endothelial proliferation (n
      = 1), perivascular inflammation (n = 3), and meningeal involvement (n = 6). All
      children were seizure free throughout postsurgical follow-up of 2-11 years. This
      first prospective study with follow-up monitoring of a childhood population with
      DNETs confirms, on a long-term basis, that the coupled strategy of extended
      lesionectomy and neuronavigation has good outcome for long-term seizure control.

PMID- 21093731
TI  - Utility of Charcot-Marie-Tooth Neuropathy Score in children with type 1A disease.
AB  - The aim of this study was to evaluate the utility of the Charcot-Marie-Tooth
      Neuropathy Score (CMTNS) for evaluation of disease severity in young children
      with Charcot-Marie-Tooth type 1A. Current validated scoring scales for Charcot
      Marie-Tooth are the CMTNS and the Neuropathy Impairment Score (NIS). Both work
      well for adult patients, and usually also for children over 10 years of age.
      There is no validation of scales for young children. Children with genetically
      proven Charcot-Marie-Tooth type 1A disease (n = 20, aged 3 to 10 years) were
      examined clinically, followed by electrophysiologic examination, and were scored
      under the CMTNS scale. The clinical symptoms were mild; the two most frequent
      symptoms were difficulty in heel walking and lower limb areflexia. The score was
      maximally abnormal in four of the nine categories. Categories for sensation,
      sensory symptoms, and motor symptoms of the arms were normal in all cases. The
      score was below 8 for all tested children. To conclude, the CMTNS in children
      aged 10 years and younger has limited sensitivity; out of nine categories, only
      four are useful. Thus, evaluation of disease severity and progression in young
      children with Charcot-Marie-Tooth disease remains limited, and there is need for
      other, effective scoring systems.

PMID- 21093730
TI  - Initial and long-term effects of cloxazolam with intractable epilepsy.
AB  - Cloxazolam has been used mainly as an anxiolytic agent. The present study was
      designed to evaluate the effectiveness of cloxazolam as an add-on antiepileptic
      drug in patients with intractable epilepsy. A total of 32 patients with
      intractable epilepsy were treated with cloxazolam: 13 with generalized epilepsy,
      15 with focal epilepsy, and 4 with undetermined type of epilepsy. The initial
      effects were evaluated at 1 month after reaching a maintenance dose (0.3-0.5
      mg/kg). The long-term effects were investigated at 2 years after reaching a
      maintenance dose. With cloxazolam, seizure frequency was reduced by >= 50% in
      19/32 patients (59%) during initial therapy and in 6/23 patients (26%) during
      long-term therapy. Two became seizure free throughout the cloxazolam therapy.
      During initial therapy, 8/32 patients (25%) developed 11 episodes of adverse
      events during the initial therapy, including 5 with drowsiness, 3 with
      hyperactivity, 2 with irritability, and 1 with loss of appetite. During long-term
      therapy, 2/23 (9%) developed drowsiness. The mean dose of cloxazolam in patients
      with an effective response was 0.30 +/- 0.18 mg/kg for initial therapy and 0.26
      +/- 0.20 mg/kg for long-term therapy. Seven of the 19 effective responders
      developed tolerance (37%). Cloxazolam is an effective and safe antiepileptic drug
      for intractable epilepsy.

PMID- 21093732
TI  - Atypical benign partial epilepsy: recognition can prevent pseudocatastrophe.
AB  - To characterize and distinguish atypical benign partial epilepsy of childhood
      among various epileptic syndromes, we conducted a clinical and
      electroencephalogram study. Seventeen children with atypical benign partial
      epilepsy of childhood were followed at our hospital. They all underwent a
      video/polygraphic study of characteristic daily seizures, facilitating a
      diagnosis of atypical benign partial epilepsy of childhood. Their clinical and
      electroencephalogram features were retrospectively analyzed. A video/polygraphic
      study indicated negative motor seizures including epileptic negative myoclonus,
      atonic absence seizures, or atonic seizures corresponding to spike-and-wave
      complexes arising from centro-parieto-temporal regions. Early in the clinical
      course, these seizures appeared every 4 +/- 2 months, and lasted 1-3 months.
      Interictal sleep electroencephalograms, initially localizing in the centro
      parieto-temporal regions, became widespread and displayed continuous, diffuse,
      spike-and-wave complexes, although the spike-wave index did not exceed 85%.
      Negative motor seizures responded to ethosuximide, corticotropin, and high-dose
      steroid, whereas other antiepileptic drugs were much less effective. All patients
      ultimately entered remission before age 12 years. Patients with atypical benign
      partial epilepsy of childhood exhibited a characteristic clinical course, and
      responded favorably to anti-absence treatment. Atypical benign partial epilepsy
      of childhood should be recognized as a discrete epileptic syndrome. Its early
      diagnosis leads to the prevention of pseudocatastrophe.

PMID- 21093733
TI  - Childhood periodic syndromes: a population-based study.
AB  - The objective of the present study was to estimate the prevalence and relative
      risk of symptoms suggestive of childhood periodic syndrome in migraine, migraine
      subtypes, and tension-type headache, relative to control subjects. The target
      population was all children (age 5-12 years) enrolled in public elementary
      schools in one Brazilian city (n = 2173). Consent was obtained for 1994 children;
      analyzable data were available for 1906 children, for a final sample of 1113
      children with migraine, tension-type headache, or no headache. Parents were
      interviewed using validated questionnaires. Headache diagnosis was assigned
      according to the International Classification of Headache Disorders, 2nd edition.
      Relative risk of symptoms was drawn by headache categories relative to controls.
      For episodic migraine, the relative risk of all symptoms except nocturnal
      enuresis was significantly increased: motion sickness, recurrent limb pain,
      recurrent abdominal pain, and parasomnias, such as sleep talking, somnambulism,
      and bruxism. For tension-type headache, only nocturnal enuresis and motion
      sickness were not more common than in controls. In multivariate analyses, any
      interictal symptom was independently associated with any headache (P < 0.001),
      migraine headaches (P < 0.001), and tension-type headaches (P < 0.01). These
      findings indicate that interictal symptoms suggestive of childhood periodic
      syndromes are common in the population, and are associated with migraine and
      specific migraine subtypes, but also with tension-type headache.

PMID- 21093734
TI  - Influenza A induced acute autonomic neuropathy in an adolescent.
AB  - Influenza A may cause serious neurologic complications, but an autoimmune
      autonomic ganglionopathy has rarely been reported. Autoantibodies that impair
      synaptic transmission in the autonomic ganglia may cause orthostatic hypotension,
      gastrointestinal dysmotility, and sudomotor dysfunction. A 15-year-old girl
      developed severe and persisting orthostatic hypotension during influenza A
      infection. Removal of circulating antibodies by a single course of intravenous
      immunoglobulin resulted in rapid and complete recovery.

PMID- 21093735
TI  - Electroconvulsive therapy for pediatric malignant catatonia with cerebellar
      dysgenesis.
AB  - Electroconvulsive therapy was successfully used to treat malignant catatonia in a
      15-year-old male patient with congenital dysgenesis of the left hemisphere of the
      cerebellum and hypoplasia of the vermis and left pons due to a presumed cerebral
      vascular accident in utero. The patient experienced significant motor and
      communication delays with mild cognitive impairment, but was otherwise in good
      health until age 15 years, when he developed rigidity, posturing, stupor,
      unresponsiveness, repetitive self-injurious behaviors, and negativism, as well as
      autonomic abnormalities including profuse diaphoresis and flushing episodes, thus
      meeting criteria for malignant catatonia. After initial response to lorazepam,
      the patient required electroconvulsive therapy for resolution of malignant
      catatonia. The case supports the safe and efficacious usage of electroconvulsive
      therapy for catatonia in adolescents with cerebellar and other developmental
      disorders. The role of the cerebellum in catatonia is also reviewed.

PMID- 21093736
TI  - Henoch-Schonlein purpura in a child with Guillain-Barre syndrome.
AB  - A case of Henoch-Schonlein purpura with Guillain-Barre syndrome in a 3-year-old
      girl is presented. This association is extremely rare. During the course of
      Guillain-Barre syndrome, a decrease in plasma factor XIII activity was noted.
      When the Guillain-Barre symptoms improved, the factor XIII activity returned to
      normal. In the present case of Henoch-Schonlein purpura complicated by Guillain
      Barre syndrome, the factor XIII level was measured, a novel feature of this
      study. The findings suggest the involvement of factor XIII, which is
      characteristically involved in Henoch-Schonlein purpura, also is involved in the
      associated Guillain-Barre syndrome.

PMID- 21093737
TI  - Failure of a clot retrieval device in an adolescent stroke patient.
AB  - A previously healthy 14-year-old boy collapsed after a football game, with
      aphasia and right hemiparesis. Cranial magnetic resonance imaging and magnetic
      resonance angiography revealed left middle cerebral artery distribution ischemic
      infarct with thrombus and possible dissection at the horizontal segment of the
      middle cerebral artery. The patient was treated 9 hours after collapse with intra
      arterial tissue plasminogen activator, but without success. The Merci clot
      retrieval device was then used, but the device broke in the middle cerebral
      artery and led to complete occlusion. At follow-up 3 months later, the boy had
      persistent aphasia, but notable improvement in his right hemiparesis. This is a
      novel report of a complication of mechanical clot retrieval treatment in a child.
      Further research is needed to determine the safety and effectiveness of
      intracranial endovascular clot retrieval devices in children.

PMID- 21093738
TI  - Dandy-Walker malformation: a rare association with hypoparathyroidism.
AB  - Dandy-Walker malformation is characterized by cystic dilatation of the fourth
      ventricle and an enlarged posterior cranial fossa with upward displacement of the
      tentorium, lateral sinuses, and torcular, with agenesis or hypoplasia of the
      cerebellar vermis. Dandy-Walker malformation occurs in approximately the 4th week
      of gestation and is associated with various abnormalities involving the cardiac,
      skeletal, genitourinary, and gastrointestinal systems. The parathyroid gland also
      forms in the 3rd and 4th gestational weeks. Reported here is the case of a male
      infant with Dandy-Walker malformation with ventricular and atrial septal defect,
      unilateral renal agenesis, and hypoparathyroidism. To our knowledge, this rare
      association with neural crest events during the development of Dandy-Walker
      malformation has not been reported previously.

PMID- 21093739
TI  - Unusual presentation of brain aspergillosis in chronic granulomatous disease.
AB  - Aspergillus is a frequently observed pathogen in patients with chronic
      granulomatous disease. We report on a patient with chronic granulomatous disease
      and severe brain aspergillosis with an unusual presentation and favorable course.
      We discuss the impact of this infection on morbidity and mortality, adequate
      therapeutic management, and the need to investigate a possible fungal infection,
      despite nonspecific signs.

PMID- 21093740
TI  - Foreword: Cosmetic procedures in gynecology.

PMID- 21093741
TI  - Preface: Cosmetic procedures in gynecology.

PMID- 21093742
TI  - Adding aesthetics to the OB-GYN practice.
AB  - Laser aesthetic procedures have substantially increased in popularity for both
      women and men over the past several years. As public awareness grows, so does the
      demand for the safe and effective delivery of these services. Gynecologists and
      other primary care providers are offering laser aesthetic procedures to meet
      their own patient demand.

PMID- 21093743
TI  - Laser hair removal.
AB  - Laser hair removal is a rapidly growing aesthetic procedure requested
      predominantly by women. At a time of falling reimbursement by payers,
      gynecologists have an opportunity to improve the fiscal health of their practices
      while delivering a service valued by their patients. As a result, practicing
      gynecologists should become acquainted with aesthetic lasers and should know how
      to incorporate them into their practices. This article introduces the practicing
      gynecologist to aesthetic lasers and the procedure of laser hair removal.

PMID- 21093744
TI  - Intense pulsed light therapy.
AB  - Intense Pulsed Light (IPL) is an FDA-approved photo therapy for the treatment of
      a variety of conditions such as acne and hirsutism. It utilizes the principle of
      selective photothermolysis. Photothermolysis allows a specific wavelength to be
      delivered to a chromophore of a designated tissue while leaving the surrounding
      tissue unaffected. The results of IPL are similar to that of laser treatments but
      it offers the advantage of a relative low cost. It is a safe and rapid treatment
      with minimal discomfort to the patient.

PMID- 21093745
TI  - Laser vein therapy.
AB  - Similar to other antiaging procedures like Botox, skin rejuvenation, and facial
      plastic surgery, spider vein therapy is seen as a way to reverse the signs of
      aging. This article will introduce the clinician to this issue and describe
      treatment, which may be accomplished with the same lasers used for laser hair
      reduction.

PMID- 21093746
TI  - Liposuction.
AB  - Liposuction is the most common cosmetic surgical procedure worldwide. It provides
      effective contouring of the torso, extremities, and submental areas in properly
      selected patients. Tumescent liposuction, a local anesthesia technique, and
      superwet liposuction, a systemic anesthesia technique, are the most common
      methods. The safety profile of both methods is excellent, but local anesthesia
      avoids the specific risks associated with general anesthesia. The most common
      complications of liposuction are contour irregularities and transient bruising.
      No technology seems to provide superior results over conventional methods.

PMID- 21093747
TI  - The use of autologous fat for facial rejuvenation.
AB  - Adding volume to the aging face is a notion that has come into vogue as of late
      but is, however, not a new idea. With the advent of miro-liposuction techniques,
      there is renewed interest in the use of aspirated fat. Commercial fillers have a
      valuable place in the cosmetic surgeon's armamentarium and offer immediate volume
      correction with a more modest financial commitment. Nevertheless, the
      standardization of fat grafting techniques marks an exciting shift in facial
      aesthetics with the ability to correct all aspects of the aging face with safe,
      natural, and lasting results.

PMID- 21093748
TI  - Breast augmentation.
AB  - Breast augmentation is the most commonly performed cosmetic procedure among
      American women. Saline implants, silicone implants, and autologous fat injections
      are the most common options. The inframammary, periareolar, and axillary routes
      with or without endoscopy are the most common routes of implantation. The
      subpectoral dual-plane and the subglandular plane are the most common pockets.
      The most common complications are capsular contracture for implants and volume
      loss for injected fat. Breast augmentation does not appear to increase breast
      cancer risk or survival rates.

PMID- 21093749
TI  - Cosmeceuticals: practical applications.
AB  - Cosmeceuticals are topically applied products that are more than merely cosmetic,
      yet are not true drugs that have undergone rigorous placebo controlled studies
      for safety and efficacy. There are many review articles that outline the
      theoretical biologic and clinical actions of these cosmeceuticals and their
      various ingredients. This article reviews how to incorporate various
      cosmeceuticals into the treatment regime of patients, depending on the diagnosis
      and therapies chosen. The practical application of when, why, and on whom to use
      different products will enable dermatologists to improve the methodology of
      product selection and, ultimately, improve patient's clinical results.

PMID- 21093750
TI  - Botulinum toxin in facial rejuvenation: an update.
AB  - Since its initial approval by the US Food and Drug Administration (FDA) 20 years
      ago for the treatment of strabismus, hemifacial spasm, and blepharospasm in
      adults, botulinum toxin (BTX) has become one of the most frequently requested
      products in cosmetic rejuvenation around the world. After years of clinical
      success and consistent safety in the upper face, the use of BTX has expanded and
      evolved to include increasingly complicated indications. In the hands of adept
      injectors, the focus has shifted from the treatment of individual dynamic
      rhytides to shaping, contouring, and sculpting, alone or in combination with
      other cosmetic procedures, to enhance the aesthetic appearance of the face.
      Although recent reports have questioned the safety of BTX, 25 years of
      therapeutic and over 20 years of cosmetic use has demonstrated an impressive
      record of safety and efficacy when used appropriately by experienced injectors.

PMID- 21093751
TI  - Advanced imaging in gastroenterology. Preface.

PMID- 21093752
TI  - Autofluorescence and narrow band imaging in Barrett's esophagus.
AB  - This review discusses the application of 2 novel imaging techniques in Barrett's
      esophagus: autofluorescence imaging and narrow band imaging (NBI).
      Autofluorescence as well as NBI may help to direct endoscopic therapy for early
      neoplasia in Barrett's esophagus; their value in daily practice, however, seems
      to be limited and needs further evaluation.

PMID- 21093753
TI  - Endomicroscopy of Barrett's Esophagus.
AB  - Endomicroscopy is a remarkable technical advance in gastrointestinal mucosa
      imaging. In 2003, Kiesslich and colleagues described the first human use of
      contrast-aided confocal laser endomicroscopy (CLE) as a novel technique for in
      vivo microscopic imaging of the gastrointestinal mucosa. Both probe-based and
      endoscope-based systems have been applied to many gastrointestinal disorders,
      including Barrett's esophagus (BE) and associated neoplasia. Probe-based confocal
      laser endomicroscopy can be used in conjunction with highresolution white light
      endoscopy and other contrast enhancement techniques. It has proven high accuracy
      for prediction of high-grade neoplasia and cancer. In vivo imaging of both flat
      BE and mucosal lesions can influence diagnosis and thereby impact upon decision
      making regarding tissue sampling and endoscopic therapy. This article discusses
      the scientific literature related to clinical use of CLE for BE, the techniques
      for performing CLE in the esophagus, and the potential future directions for CLE
      in BE and esophageal cancer diagnosis and treatment.

PMID- 21093754
TI  - High-definition endoscopy and magnifying endoscopy combined with narrow band
      imaging in gastric cancer.
AB  - Gastric cancer is the third common cancer and is the second leading cause of
      cancer deaths worldwide. Endoscopy is being increasingly used for gastric cancer
      screening because of a high detection rate. Despite promising data, the technique
      depends heavily on the availability of endoscopic instruments and expertise for
      mass screening. Furthermore, the introduction of various new endoscopic devices
      and techniques may enhance the value of endoscopy in efficacious cancer
      screening. High-definition endoscopy and image-enhanced endoscopy, including
      narrow band imaging, are the key modalities in advanced endoscopic imaging in
      gastric cancer.

PMID- 21093755
TI  - Endomicroscopy of intestinal metaplasia and gastric cancer.
AB  - In vivo histologic diagnosis of gastric intestinal metaplasia (GIM) and gastric
      cancer (GC) can be achieved by confocal laser endomicroscopy (CLE). This review
      describes the endomicroscopic features of GIM and GC and reviews their clinical
      applications. Differentiation of phenotypes of GIM and GC by using CLE is also
      discussed.

PMID- 21093756
TI  - How to approach the small bowel with flexible enteroscopy.
AB  - Nowadays, 5 nonsurgical flexible endoscopic techniques are available for small
      bowel endoscopy: push enteroscopy (PE), balloon-assisted enteroscopy using 2
      balloons (double-balloon enteroscopy [DBE]) or 1 balloon (single-balloon
      enteroscopy [SBE]), balloon-guided enteroscopy (BGE), and spiral enteroscopy
      (SE). PE is a cost-saving, easy, and fast procedure for the examination of the
      proximal jejunum, but for a deep small bowel endoscopy, the other flexible
      enteroscopic techniques are required. BGE does not play a considerable role in
      deep small bowel endoscopy. DBE is the oldest flexible enteroscopic technique.
      Actually, the balloon-assisted enteroscopy (BAE) techniques with one balloon
      (SBE) or two balloons (DBE) are the mainly used techniques. DBE has become
      established throughout the world for diagnostic and therapeutic examinations of
      the small bowel and is now used universally in clinical routine work. DBE is
      still regarded as the gold standard nonsurgical procedure for deep small bowel
      endoscopy, because it provides the highest rates of complete enteroscopy, which
      becomes increasingly useful. The recently introduced SE technique represents a
      promising method but still needs technical improvement. Larger prospective
      studies on SE and prospective studies comparing the 3 systems (DBE, SBE, SE) are
      awaited before conclusive assessments can be made.

PMID- 21093757
TI  - Video capsule endoscopy: what is the future?
AB  - Video capsule endoscopy (VCE) that was launched 10 years ago has become a first
      line procedure for examining the small bowel, especially in the case of obscure
      gastrointestinal bleeding. Other major indications include Crohn disease (CD),
      celiac disease, and intestinal polyposis syndrome. In the case of small bowel
      diseases, the use of VCE must be integrated in a global diagnostic and
      therapeutic approach. More recently, wireless endoscopy has been adapted for
      examining the colon, opening up larger perspectives for colorectal cancer
      screening or colon examination. Technologic modifications of the second
      generation colon capsule increase the sensitivity of this method for detecting
      polyps. Other new developments, including remote magnetic manipulation, power
      management, drug delivery capsule, microbiopsy capsule, and adaptation of
      technologies such as chromoendoscopy, are sure to enhance the capabilities of
      wireless endoscopy in gastrointestinal disorders.

PMID- 21093758
TI  - New options of cholangioscopy.
AB  - In the evaluation of biliary diseases, cholangioscopy is considered as
      complementary procedure to radiographic imaging. Direct visualization of the bile
      duct is the premier advantage of cholangioscopy over indirect imaging techniques.
      However, cholangioscopy has not gained wide acceptance because of several
      technical limitations such as scope fragility, impaired steerability, limited
      irrigation, and suction capabilities, as well as the need for two experienced
      endoscopists. Recent innovations such as the implementation of electronic video
      cholangioscopes and the development of single-operator systems facilitate the
      procedure, and promise to increase the diagnostic and therapeutic yield of
      cholangioscopy.

PMID- 21093759
TI  - Contrast-enhanced and 3-dimensional endoscopic ultrasonography.
AB  - Recent progress of the data processing applied to ultrasonographic (US)
      examination has made it possible to develop new software. The US workstation of
      the last generation thus incorporated in their center a computer allowing a
      precise treatment of the US image. This advancement has made it possible to work
      out new images such as 3-dimensional (3D) US, contrast harmonic US associated
      with the intravenous injection of contrast agents, and even more recently,
      elastography. These techniques, quite elaborate in percutaneous US at present,
      are to be adapted and evaluated with endoscopic US (EUS). The contribution of
      contrast agents of US to pancreatic EUS and then 3D EUS are successively
      approached in this article.

PMID- 21093760
TI  - High-definition and filter-aided colonoscopy.
AB  - New high-resolution colonoscopes and filter technologies are allowing us to
      visualize more lesions and better characterize lesions within the
      gastrointestinal tract. In light of recent findings that flat and serrated
      lesions are more likely to contain invasive cancer and that even small lesions (5
      10 mm) may contain advanced histology, detecting these lesions earlier with
      improved optical technologies may help decrease the rate of interval cancers
      after colonoscopy. With the limited accuracy of white-light colonoscopy (59%-84%)
      in distinguishing non-neoplastic lesions from neoplastic lesions, these new
      technologies can help us improve our abilities to risk stratify patients and
      determine more precise surveillance intervals.

PMID- 21093761
TI  - Wide view and retroview during colonoscopy.
AB  - Colonoscopy is the best imaging device currently available for the detection of
      lesions in the large bowel, but may be an imperfect tool against colon cancer.
      Because recent guidelines for colorectal cancer screening and surveillance depend
      on whether polyps are found on colonoscopy and on their size, the need to
      identify all the neoplasia in the colon has assumed greater importance. This
      article reviews and assesses the latest developments in colonoscopy including
      wide-angle optics, endoscope caps and hoods, retroflexion and the use of the
      third eye retroscope.

PMID- 21093762
TI  - Computed tomographic colonography: ready for prime time?
AB  - Computed tomographic (CT) colonography is a noninvasive method to evaluate the
      colon and has received considerable attention in the last decade as a colon
      imaging tool. The technique has also been proposed as a potential primary colon
      cancer-screening method in the United States. The accuracy of the technique for
      the detection of large lesions seems to be high, perhaps in the range of
      colonoscopy. Overall, the field is rapidly evolving. Available data suggest that
      CT colonography, although a viable colon cancer screening modality in the United
      States, is not ready for widespread implementation, largely because of the lack
      of standards for training and reading and the limited number of skilled readers.

PMID- 21093763
TI  - Molecular imaging: interaction between basic and clinical science.
AB  - One of the major proceedings in the field of gastrointestinal endoscopy has been
      the advent of molecular imaging, which possesses the potential to have a
      significant effect on the existing diagnostic and therapeutic paradigms.
      Molecular imaging encompasses different methods that enable the visualization of
      disease-specific morphologic or functional alterations of the mucosa based on the
      molecular signature of individual cells. This development has been made possible
      by advancements in basic science coupled with technological innovations in
      endoscopy, both facilitating the identification and characterization of mucosal
      lesions in vivo based on the lesions' molecular composition rather than their
      morphologic structure alone. Novel studies based on fluorescent antibody imaging
      pave the road toward clinical translation and give hope for improved diagnosis
      and targeted therapies in gastrointestinal diseases.

PMID- 21093764
TI  - Molecular imaging of gastroenteropancreatic neuroendocrine tumors.
AB  - Somatostatin-receptor scintigraphy has become an obligatory molecular imaging
      method in the management of patients with neuroendocrine tumors when metastatic
      disease is suspected. Using positron emission tomography and new somatostatin
      analogues, sensitivity of somatostatin receptor imaging has further increased.
      With a combination of morphologic imaging methods, such as hybrid imaging by
      PET/CT, this method represents the method of choice in many centers and efforts
      are under way to translate somatostatin receptor imaging onto a cellular level by
      endoscopic confocal microscopy. Other clinically relevant functional pathways in
      neuroendocrine tumors that are accessible by PET imaging are glucose metabolism
      and amine precursor uptake and decarboxylation.

PMID- 21093765
TI  - Abstract thinking: environmental modification, development, and psychopathology.

PMID- 21093766
TI  - The field of toddler/preschool mental health has arrived--on a global scale.

PMID- 21093767
TI  - Evaluating the quality of community care for attention-deficit/hyperactivity
      disorder.

PMID- 21093768
TI  - Developmental neuroimaging studies of OCD: the maturation of a field.

PMID- 21093769
TI  - Neurobiology of the adolescent brain and behavior: implications for substance use
      disorders.
AB  - OBJECTIVE: Adolescence is a developmental period that entails substantial changes
      in risk-taking behavior and experimentation with alcohol and drugs. Understanding
      how the brain is changing during this period relative to childhood and adulthood
      and how these changes vary across individuals are key in predicting risk for
      later substance abuse and dependence. METHOD: This review discusses recent human
      imaging and animal work in the context of an emerging view of adolescence as
      characterized by a tension between early emerging "bottom-up" systems that
      express exaggerated reactivity to motivational stimuli and later maturing "top
      down" cognitive control regions. Behavioral, clinical, and neurobiological
      evidences are reported for dissociating these two systems developmentally. The
      literature on the effects of alcohol and its rewarding properties in the brain is
      discussed in the context of these two systems. RESULTS: Collectively, these
      studies show curvilinear development of motivational behavior and the underlying
      subcortical brain regions, with a peak inflection from 13 to 17 years. In
      contrast, prefrontal regions, important in top-down regulation of behavior, show
      a linear pattern of development well into young adulthood that parallels that
      seen in behavioral studies of impulsivity. CONCLUSIONS: The tension or imbalance
      between these developing systems during adolescence may lead to cognitive control
      processes being more vulnerable to incentive-based modulation and increased
      susceptibility to the motivational properties of alcohol and drugs. As such,
      behavior challenges that require cognitive control in the face of appetitive cues
      may serve as useful biobehavioral markers for predicting which teens may be at
      greater risk for alcohol and substance dependence.

PMID- 21093770
TI  - Genetically informative research on adolescent substance use: methods, findings,
      and challenges.
AB  - OBJECTIVE: To provide an overview of the genetic epidemiology of substance use
      and misuse in adolescents. METHOD: A selective review of genetically informative
      research strategies, their limitations, and key findings examining issues related
      to the heritability of substance use and substance use disorders in children and
      adolescents is presented. RESULTS: Adoption, twin, and extended-family designs
      have established there is a strong heritable component to liability to nicotine,
      alcohol, and illicit drug dependence in adults. However, shared environmental
      influences are relatively stronger in youth samples and at earlier stages of
      substance involvement (e.g., use). There is considerable overlap in the genetic
      influences associated with the abuse/dependence across drug classes, and shared
      genetic influences contribute to the commonly observed associations between
      substance-use disorders and externalizing and, to a lesser extent, internalizing
      psychopathology. Rapid technologic advances have made the identification of
      specific gene variants that influence risks for substance-use disorders feasible,
      and linkage and association (including genomewide association studies) have
      identified promising candidate genes implicated in the development of substance
      use disorders. CONCLUSIONS: Studies using genetically informative research
      designs, including those that examine aggregate genetic factors and those
      examining specific gene variants, individually and in interaction with
      environmental influences, offer promising avenues not only for delineating
      genetic effects on substance-use disorders but also for understanding the
      unfolding of risk across development and the interaction between environmental
      and genetic factors in the etiology of these disorders.

PMID- 21093771
TI  - Preschool psychopathology reported by parents in 23 societies: testing the seven
      syndrome model of the child behavior checklist for ages 1.5-5.
AB  - OBJECTIVE: To test the fit of a seven-syndrome model to ratings of preschoolers'
      problems by parents in very diverse societies. METHOD: Parents of 19,106 children
      18 to 71 months of age from 23 societies in Asia, Australasia, Europe, the Middle
      East, and South America completed the Child Behavior Checklist for Ages 1.5-5
      (CBCL/1.5-5). Confirmatory factor analyses were used to test the seven-syndrome
      model separately for each society. RESULTS: The primary model fit index, the root
      mean square error of approximation (RMSEA), indicated acceptable to good fit for
      each society. Although a six-syndrome model combining the Emotionally Reactive
      and Anxious/Depressed syndromes also fit the data for nine societies, it fit less
      well than the seven-syndrome model for seven of the nine societies. Other fit
      indices yielded less consistent results than the RMSEA. CONCLUSIONS: The seven
      syndrome model provides one way to capture patterns of children's problems that
      are manifested in ratings by parents from many societies. Clinicians working with
      preschoolers from these societies can thus assess and describe parents' ratings
      of behavioral, emotional, and social problems in terms of the seven syndromes.
      The results illustrate possibilities for culture-general taxonomic constructs of
      preschool psychopathology. Problems not captured by the CBCL/1.5-5 may form
      additional syndromes, and other syndrome models may also fit the data.

PMID- 21093772
TI  - Quality of care for childhood attention-deficit/hyperactivity disorder in a
      managed care medicaid program.
AB  - OBJECTIVE: To examine whether clinical severity is greater among children
      receiving attention-deficit/hyperactivity disorder (ADHD) care in primary care
      compared with those in specialty mental health clinics, and to examine how care
      processes and clinical outcomes vary by sector across three 6-month time
      intervals. METHOD: This was a longitudinal cohort study of 530 children aged 5 to
      11 years receiving ADHD care in primary care or specialty mental health clinics
      from November 2004 through September 2006 in a large, countywide managed care
      Medicaid program. RESULTS: Clinical severity at study entry did not differ
      between children who received ADHD care in solely primary or specialty mental
      health care clinics. At three 6-month intervals, receipt of no care ranged from
      34% to 44%, and unmet need for mental health services ranged from 13% to 20%. In
      primary care, 80% to 85% of children had at least one stimulant prescription
      filled and averaged one to two follow-up visits per year. Less than one-third of
      children in specialty mental health clinics received any stimulant medication,
      but all received psychosocial interventions averaging more than five visits per
      month. In both sectors, stimulant medication refill prescription persistence was
      poor (31%-49%). With few exceptions, ADHD diagnosis, impairment, academic
      achievement, parent distress, and parent-reported treatment satisfaction,
      perceived benefit, and improved family functioning did not differ between
      children who remained in care and those who received no care. CONCLUSION: Areas
      for quality improvement are alignment of clinical severity with provider type,
      follow-up visits, stimulant use in specialty mental health, agency data
      infrastructure to document delivery of evidence-based psychosocial treatment, and
      stimulant medication refill prescription persistence.

PMID- 21093773
TI  - Functional magnetic resonance imaging during planning before and after cognitive
      behavioral therapy in pediatric obsessive-compulsive disorder.
AB  - OBJECTIVE: Pediatric obsessive compulsive disorder (OCD) has been associated with
      cognitive abnormalities, in particular executive impairments, and dysfunction of
      frontal-striatal-thalamic circuitry. The aim of this study was to investigate if
      planning as an executive function is compromised in pediatric OCD and is
      associated with frontal-striatal-thalamic dysfunction, and if this dysfunction
      would normalize after successful treatment. METHOD: Twenty-five medication-free
      pediatric patients (mean +/- SD 13.95 +/- 2.52 years old, range 9 to 19 years)
      with OCD and 25 healthy controls, matched by age and gender, were scanned twice
      using a self-paced pseudo-randomized event-related functional magnetic resonance
      imaging version of the Tower of London. Patients were rescanned after 16 sessions
      of protocol-based cognitive behavioral therapy; healthy controls were rescanned
      after a similar interval. RESULTS: Patients performed the task significantly
      slower but with similar accuracy compared with controls. Neuroimaging results
      showed less recruitment of frontal and parietal regions in patients with OCD
      compared with controls during the planning versus control task. With increasing
      task load patients compared with controls showed more recruitment of
      ventrolateral and medial prefrontal cortex and insula and anterior cingulate
      cortex. After treatment, these differences ceased to be significant, with time by
      group by task load interaction analyses showing a significant decrease in right
      posterior prefrontal activity in patients with OCD compared with healthy
      controls. CONCLUSION: Pediatric patients with OCD showed subtle planning
      impairments and decreased dorsolateral prefrontal and parietal recruitment that
      normalized after cognitive behavioral treatment. Planning dysfunction is likely
      to be a state rather than a trait feature of pediatric OCD.

PMID- 21093774
TI  - Altered development of white matter in youth at high familial risk for bipolar
      disorder: a diffusion tensor imaging study.
AB  - OBJECTIVE: To study white matter (WM) development in youth at high familial risk
      for bipolar disorder (BD). WM alterations are reported in youth and adults with
      BD. WM undergoes important maturational changes in adolescence. Age-related
      changes in WM microstructure using diffusion tensor imaging with tract-based
      spatial statistics in healthy offspring having a parent with BD were compared
      with those in healthy controls. METHOD: A total of 45 offspring participated,
      including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25
      healthy control offspring of healthy parents (CONT). All were free of medical and
      psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD),
      and longitudinal diffusivity were examined using whole-brain analyses, co-varying
      for age. RESULTS: Group-by-age interactions showed a linear increase in FA and a
      linear decrease in RD in CONT in the left corpus callosum and right inferior
      longitudinal fasciculus. In HBO, there was a linear decrease in FA and an
      increase in RD with age in the left corpus callosum and no relation between FA or
      RD and age in the right inferior longitudinal fasciculus. Curve fitting confirmed
      linear and showed nonlinear relations between FA and RD and age in these regions
      in CONT and HBO. CONCLUSIONS: This is the first study to examine WM in healthy
      offspring at high familial risk for BD. Results from this cross-sectional study
      suggest altered development of WM in HBO compared with CONT in the corpus
      callosum and temporal associative tracts, which may represent vulnerability
      markers for future BD and other psychiatric disorders in HBO.

PMID- 21093775
TI  - Combined diffusion tensor imaging and transverse relaxometry in early-onset
      bipolar disorder.
AB  - OBJECTIVE: Transverse relaxation time (T2) imaging provides the opportunity to
      examine membrane fluidity, which can affect a number of cellular functions. The
      objective of the present work was to examine T2 abnormalities in children with
      unmodified DSM-IV-TR bipolar disorder (BD) in bilateral cingulate-paracingulate
      (CPC) white matter. METHOD: A total of 21 children and adolescents with BD and 16
      healthy control subjects underwent magnetic resonance imaging at 1.5 Tesla and
      were compared using a region-of-interest analysis. A post hoc diffusion tensor
      imaging (DTI) analysis was also performed on selected subjects. RESULTS: The T2
      values were significantly decreased on the right-side of the subjects with BD
      compared with that of the control subjects. Hemispheric difference was also
      observed in the BD group, with decreased T2 on the right side compared with the
      left side. No significant difference was observed between left and right CPC T2
      in control subjects. For participants who had both T2 and DTI measurements,
      significant DTI differences were observed: On the left side, fractional
      anisotropy was reduced and trace and radial diffusivity were increased, whereas
      on the right side, trace was increased and T2 was decreased in subjects with BD
      compared with control subjects. CONCLUSIONS: Our findings suggest that the
      observed T2 difference is a reflection of cerebral blood flow rather than an
      alteration of the fluidity of cell membranes. It is possible that myelin damage
      occurs on the left side in early-onset BD, in addition to changes in the blood
      flow. Prospective studies with larger numbers of subjects are warranted to
      further explore the relevance of the presented results.

PMID- 21093778
TI  - Hats off: 2010 Journal awards.

PMID- 21093779
TI  - Re-covered, coordinated, e-volved: editor's annual report--Volume 49, 2010.

PMID- 21093776
TI  - White matter compromise of callosal and subcortical fiber tracts in children with
      autism spectrum disorder: a diffusion tensor imaging study.
AB  - OBJECTIVE: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of
      functional networks, highlighting the importance of investigating white matter
      and interregional connectivity. We used diffusion tensor imaging (DTI) to examine
      white matter integrity for the whole brain and for corpus callosum, internal
      capsule, and middle cerebellar peduncle in children with ASD and typically
      developing (TD) children. METHOD: DTI data were obtained from 26 children with
      ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity
      (MD), and axial and radial diffusion were calculated for the whole brain, the
      genu, body, and splenium of the corpus callosum, the genu and anterior and
      posterior limbs of the internal capsule, and the middle cerebellar peduncle.
      RESULTS: Children with ASD had reduced FA and increased radial diffusion for
      whole-brain white matter and all three segments of the corpus callosum and
      internal capsule, compared with those in TD children. Increased MD was found for
      the whole brain and for anterior and posterior limbs of the internal capsule.
      Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was
      also found for the middle cerebellar peduncle. CONCLUSIONS: Our findings suggest
      widespread white matter compromise in children with ASD. Abnormalities in the
      corpus callosum indicate impaired interhemispheric transfer. Results for the
      internal capsule and middle cerebellar peduncle add to the currently limited DTI
      evidence on subcortico-cortical tracts in ASD. The robust impairment found in all
      three segments of the internal capsule is consistent with studies documenting
      impairment of elementary sensorimotor function in ASD.

PMID- 21093782
TI  - Assessment of selenium bioavailability from naturally produced high-selenium soy
      foods in selenium-deficient rats.
AB  - We assessed the bioavailability of selenium (Se) from a protein isolate and tofu
      (bean curd) prepared from naturally produced high-Se soybeans. The Se
      concentrations of the soybeans, the protein isolate and tofu were 5.2+/-0.2,
      11.4+/-0.1 and 7.4+/-0.1mg/kg, respectively. Male weanling Sprague-Dawley rats
      were depleted of Se by feeding them a 30% Torula yeast-based diet (4.1MUg Se/kg)
      for 56 days, and then they were replenished with Se for an additional 50 days by
      feeding them the same diet containing 14, 24 or 30 MUg Se/kg from the protein
      isolate or 13, 23 or 31 MUg Se/kg from tofu, respectively. l-Selenomethionine
      (SeMet) was used as a reference. Selenium bioavailability was determined on the
      basis of the restoration of Se-dependent enzyme activities and tissue Se
      concentrations in Se-depleted rats, comparing those responses for the protein
      isolate and tofu to those for SeMet by using a slope-ratio method. Dietary
      supplementation with the protein isolate or tofu resulted in linear or log
      linear, dose-dependent increases in glutathione peroxidase activities in blood
      and liver and in thioredoxin reductase activity in liver. Furthermore,
      supplementation with the protein isolate or tofu resulted in linear or log
      linear, dose-dependent increases in the Se concentrations of plasma, liver,
      muscle and kidneys. These results indicated an overall bioavailability of
      approximately 101% for Se from the protein isolate and 94% from tofu, relative to
      SeMet. We conclude that Se from naturally produced high-Se soybeans is highly
      bioavailable in this model and that high-Se soybeans may be a good dietary source
      of Se.

PMID- 21093783
TI  - Meiotic sex chromosome inactivation.

PMID- 21093784
TI  - Hydra.

PMID- 21093785
TI  - The natural history of Caenorhabditis elegans.

PMID- 21093786
TI  - Estimating human age from T-cell DNA rearrangements.

PMID- 21093787
TI  - Sexual dimorphism: why the sexes are (and are not) different.
AB  - Sex differences often call sexual selection to mind; however, a new damselfly
      study cautions on being too hasty, and implicates viability selection in the
      evolution of male and female colouration.

PMID- 21093788
TI  - Vascular lumen formation: negativity will tear us apart.
AB  - Functional blood vessels are essential for vertebrate development, but how
      endothelial cells initiate lumen formation during vasculogenesis is not known. A
      new study now reveals that electrostatic repulsion is key.

PMID- 21093789
TI  - Numerical processing: stimulating numbers.
AB  - A new study using transcranial direct current stimulation shows that modulating
      parietal cortex activity during the learning of abstract numerical material can
      enhance numerical competency for up to six months.

PMID- 21093790
TI  - Evolution: plastic sociality in a sweat bee.
AB  - How and why do bees become social? A transplant experiment shows that sweat bees
      can adopt a solitary or social lifestyle in response to their environment.

PMID- 21093791
TI  - Gene regulation: global transcription rates scale with size.
AB  - Is bigger better? Scientists have long puzzled over the potential relationship
      between cell size and the rate of mRNA production. A recent report builds a
      strong case that global transcription rates scale with size.

PMID- 21093792
TI  - Life history: the energy-efficient orangutan.
AB  - A study of orangutans' daily energy expenditure confirmed exceptionally slow
      metabolism. It suggests they evolved a lifestyle designed to minimize energy use.
      If so, shifting to a higher energy-use strategy may help explain how humans
      evolved.

PMID- 21093793
TI  - Palaeoecology: different dinosaur ecologies in deep time?
AB  - Do dinosaurs from the Moroccan Kem Kem formation provide evidence for an
      ecosystem dramatically different from anything seen today? More likely the common
      palaeontological problem of time-averaging has had a part to play.

PMID- 21093794
TI  - Social evolution: war of the worms.
AB  - The discovery of a non-reproductive soldier caste in a clonally reproducing
      trematode greatly extends the taxonomic distribution of eusociality and reaffirms
      the importance of relatedness in the evolution of reproductive altruism.

PMID- 21093795
TI  - Signaling and transcriptional control of reproductive development in Arabidopsis.
AB  - Plant reproductive development is a complex process with diploid and haploid
      phases, including male and female organogenesis, meiosis, gametogenesis,
      pollination and fertilization. A number of regulatory mechanisms control both
      diploid and haploid cell division and differentiation, especially cell-cell
      signaling pathways mediated by receptor-linked protein kinases with prominent
      roles in early male development, and hormonal signaling pathways crucial for
      later events in male and female reproductive development. Furthermore,
      transcriptional networks control the proper formation of specific cell layers and
      embryo sac cell specification.

PMID- 21093796
TI  - The yield of routine EEG in geriatric patients: A prospective hospital-based
      study.
AB  - STUDY AIM: To study the yield of routine EEG in geriatric patients. PATIENTS AND
      METHODS: We examined standard EEG recordings of 701 patients aged 84.6+/-6.4
      years. These were performed over a 15 month-period in a geriatric hospital. The
      majority of patients were hospitalized and 46.5% suffered from multiple medical
      problems. RESULTS: We found EEG abnormalities in 392/701 (56%) patients. These
      consisted of permanent diffuse slowing, either isolated (17.1%) or with
      intermixed epileptiform abnormalities (2.4%), focal slowing (15.4%), intermittent
      diffuse slowing (8.9%), triphasic waves (1.14%), periodic epileptiform discharges
      (0.57%), flat and inactive tracing (0.14%), status epilepticus (0.99%), seizures
      (0.42%), interictal epileptiform abnormalities (8.7%). Epileptiform abnormalities
      (both ictal and interictal) were observed in 92/701 (13.1%) patients. These were
      focal in the majority of cases (85.9%), most frequent in temporal regions (42%),
      followed by centroparietal (20.2%) and temporo-parieto-occipital carrefour
      regions (17.2%), but less frequent in frontal (6.3%) and occipital regions
      (3.8%). We found sleep activity without other EEG abnormalities in 13.7% of
      patients and subclinical rhythmic electrographic discharge in adult (SREDA) in 1%
      of cases. CONCLUSIONS: In this study, EEG abnormalities were very common, which
      reflects the high frequency of cerebral dysfunction in geriatric patients. These
      abnormalities are of various types, often suggestive of different aetiologies,
      and may be helpful in clinical management.

PMID- 21093797
TI  - Revisiting P300 cognitive studies for dementia diagnosis: Early dementia with
      Lewy bodies (DLB) and Alzheimer disease (AD).
AB  - AIMS OF THE STUDY: Earlier P300 studies were conducted when the prevalence of
      dementia with Lewy Bodies (DLB) was unknown. Our study aims to examine whether
      P300 abnormalities are present in DLB and to evidence possible differences
      between DLB and Alzheimer's disease (AD). A second aim of this study is to look
      for correlations between P300 recordings and EEG, as abnormal EEG variability has
      been described in DLB. PATIENTS AND METHODS: Auditory P300 responses were
      recorded by a classic oddball paradigm in 50 controls, in 36 DLB patients, and in
      40 AD patients with MMSE>20. RESULTS: Reliable auditory P300 responses were
      obtained in 26 DLB (72%), 33 AD (82.5%), and 46 controls (92%). P300 was more
      delayed and had lower amplitude in DLB compared to AD groups. P300 topography was
      also different as the anterior-to-posterior scalp amplitude gradient was reversed
      in DLB. P300 latency correlated with neuropsychological test scores and with EEG
      variables. Gradient inversion and delayed P300 responses in frontal derivations
      evidenced differences between DLB and AD patients with a sensitivity of 70% and a
      specificity of 97%. CONCLUSIONS: P300 recordings are abnormal in DLB and can be
      useful to distinguish DLB from AD.

PMID- 21093798
TI  - [Exploration of the auditory system in humans: From click to speech auditory
      brainstem responses].
AB  - There is a growing and unprecedented interest in the objective evaluation of the
      subcortical processes that are involved in speech perception, with potential
      clinical applications in speech and language impairments. Here, we review the
      studies illustrating the development of electrophysiological methods for
      assessing speech encoding in the human brainstem: from the pioneer recordings of
      click-evoked auditory brainstem responses (ABR), via studies of frequency
      following responses (FFR) to the most recent measurements of speech ABR (SABR) or
      ABR in response to speech sounds. Recent research on SABR has provided new
      insights in the understanding of subcortical auditory processing mechanisms. The
      SABR test is an objective and non-invasive tool for assessing individual capacity
      of speech encoding in the brainstem. SABR characteristics are potentially useful
      both as a diagnosis tool of speech encoding deficits and as an assessment tool of
      the efficacy of rehabilitation programs in patients with learning and/or auditory
      processing disorders.

PMID- 21093799
TI  - EEG-NIRS in epilepsy in children and neonates.
AB  - Coregistration of EEG-near infrared spectroscopy (NIRS) is a recent technique
      used to analyse changes in both electrical and local hemodynamic activities.
      Here, we describe some technical aspects of simultaneous EEG-NIRS signal
      acquisition focusing on recent EEG-NIRS sensors, notably the Electroptode((r))TM.
      Advantages and disadvantages of simultaneous EEG-NIRS acquisition are discussed
      in comparison to other common techniques in epilepsy. Most important recent
      results are presented and discussed, notably those providing new insights into
      the mechanisms propelling neurons to synchronize, resulting in inter-critical
      spikes and different types of seizures.

PMID- 21093800
TI  - Barriers to implementing evidence-based clinical guidelines: a survey of early
      adopters.
AB  - OBJECTIVE: The purpose of this study was to identify barriers that early-adopting
      dentists perceive as common and challenging when implementing recommendations
      from evidence-based (EB) clinical guidelines. METHOD: This is a cross-sectional
      study. Dentists who attended the 2008 Evidence-based Dentistry Champion
      Conference were eligible for inclusion. Forty-three dentists (34%) responded to a
      22-item questionnaire administered online. Two investigators independently coded
      and categorized responses to open-ended items. Descriptive statistics were
      computed to assess the frequency of barriers and perceived challenges. RESULTS:
      The most common barriers to implementation were difficulty in changing current
      practice model, resistance and criticism from colleagues, and lack of trust in
      evidence or research. Barriers perceived as serious problems had to do with lack
      of up-to-date evidence, lack of clear answers to clinical questions, and
      contradictory information in the scientific literature. CONCLUSIONS: Knowledge of
      barriers will help improve translation of biomedical research for dentists.
      Information in guidelines needs to be current, clear, and simplified for use at
      chairside; dentists' fears need to be addressed.

PMID- 21093801
TI  - Assessment of publication bias in dental specialty journals.
AB  - OBJECTIVE: The purpose of this study was to investigate the presence of
      publication bias (acceptance of articles indicating statistically significant
      results). METHODS: The journals possessing the highest impact factor (2008 data)
      in each dental specialty were included in the study. The content of the 6 most
      recent issues of each journal was hand searched and research articles were
      classified into 4 type categories: cross-sectional, case-control, cohort, and
      interventional (nonrandomized clinical trials and randomized controlled trials).
      In total, 396 articles were included in the analysis. Descriptive statistics and
      univariate and multivariate logistic regression was used to examine the
      association between article-reported statistical significance (dependent
      variable) and journal impact factor and article study type subject area
      (independent variables). RESULTS: A statistically significant acceptance rate of
      positive result was found, ranging from 75% to 90%, whereas the value of impact
      factor was not related to publication bias among leading dental journals.
      Compared with other research designs, clinical intervention studies (randomized
      or nonrandomized) presented the highest percentage of nonsignificant findings
      (20%); RCTs represented 6% of the examined investigations. CONCLUSIONS: Compared
      with the Journal of Clinical Periodontology, all other subspecialty journals,
      except the Journal of Oral and Maxillofacial Surgery, showed significantly
      decreased odds of publishing an RCT, which ranged from 60% to 93% (P < .05).

PMID- 21093802
TI  - Hospital based emergency department visits attributed to dental caries in the
      United States in 2006.
AB  - OBJECTIVE: There is a paucity of published studies presenting nationally
      representative estimates on hospital-based emergency department visits primarily
      attributed to dental caries. The objective of this study is to provide estimates
      of hospital-based emergency department visits attributed to dental caries in the
      United States. METHODS: The Nationwide Emergency Department Sample, a component
      of the Healthcare Cost and Utilization Project, sponsored by the Agency for
      Healthcare Research and Quality, was used for this study. All emergency
      department visits attributable to dental caries were identified using ICD-9-CM
      diagnoses codes and selected for analysis. Outcomes including hospital charges
      and length of stay in hospital were examined. Simple descriptive statistics were
      used to summarize the data. RESULTS: This study found that in 2006, a total of
      330,757 visits to hospital-based emergency departments occurred in the United
      States. The total charges were $110 million. Approximately 45% of all visits by
      adults occurred among the uninsured. Medicaid was the most common payer for all
      visits by children, accounting for nearly 53% of all visits. About 38% of visits
      occurred among those residing in low-income areas. Hospitalization was required
      for 158 visits. CONCLUSIONS: This study provides nationwide estimates of hospital
      based emergency department visits attributed to dental caries in the United
      States. The uninsured constituted the greatest proportion of emergency department
      visits among adults, whereas Medicaid was the major payer for children visiting
      the emergency departments.

PMID- 21093803
TI  - Periodontal disease may be associated with oral and gastrointestinal cancer.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The association between periodontal
      disease and cancer:a review of the literature. Fitzpatrick SG, Katz J.J Dent
      2010;38(2):83-95. Epub 2009 Nov 4. REVIEWER: Zoann Nugent, Ph. D.
      PURPOSE/QUESTION: To assess the published research to date on the relationship
      between periodontal disease and cancer. SOURCE OF FUNDING: Information not
      available. TYPE OF STUDY/DESIGN: Comprehensive literature review. LEVEL OF
      EVIDENCE: Level 3: Other evidence. STRENGTH OF RECOMMENDATION GRADE: Grade C:
      Consensus, disease-oriented evidence, expert opinion.

PMID- 21093804
TI  - The relationship between periodontitis and alcohol use is not clear.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The relationship of alcohol
      dependence and alcohol consumption with periodontitis: a systematic review.
      Amaral Cda S, Vettore MV, Leao A. J Dent 2009;37:643-51. REVIEWER: Bruce A. Dye,
      DDS, MPH PURPOSE/QUESTION: Is alcohol use or dependence associated with
      periodontitis? SOURCE OF FUNDING: Government: authors received partial support
      from Coordination of Improvement of Higher Education Personnel (CAPES) Ministry
      of Education, Brazil TYPE OF STUDY/DESIGN: Systematic review LEVEL OF EVIDENCE:
      Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION
      GRADE: Not applicable.

PMID- 21093805
TI  - The use of a membrane and/or a bone graft may not improve the effects of enamel
      matrix derivatives in infrabony defects.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Do bone grafts or barrier membranes
      provide additional treatment effects for intrabony lesions treated with enamel
      matrix derivatives? A network meta-analysis of randomized controlled trails. Tu Y
      K, Woolston A, Faggion CM Jr. J Clin Periodontol 2010;37:59-79. REVIEWER: Simone
      Verardi, DDS, MSD. PURPOSE/QUESTION: Do membranes and bone grafts improve the
      outcomes in the treatment of intrabony defects when they are used in combination
      with enamel matrix derivatives? SOURCE OF FUNDING: Government: Higher Education
      Funding Council for England (HEFCE) and United Kingdom Research Council
      Fellowship. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.
      LEVEL OF EVIDENCE: Level 2: Limited-quality patient-oriented evidence. STRENGTH
      OF RECOMMENDATION GRADE: Grade B: Inconsistent or limited-quality patient
      oriented evidence.

PMID- 21093806
TI  - Povidone-iodine may provide small adjunctive benefit to scaling and root planing.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Systematic review on the effect of
      rinsing with povidone-iodine during nonsurgical therapy. Sahrmann P, Puhan MA,
      Attin T, Scmidlin PR. J Periodontal Res 2010;45:153-64. REVIEWER: Mark V. Thomas,
      DMD. PURPOSE/QUESTION: In patients with chronic periodontitis, does intrasulcular
      irrigation with povidone-iodine (PVP-I) offer an adjunctive benefit over
      conventional scaling and root planing (SRP)? SOURCE OF FUNDING: None disclosed.
      TYPE OF STUDY DESIGN: Systematic review with meta-analysis LEVEL OF EVIDENCE:
      Level 3: Other evidence. STRENGTH OF RECOMMENDATION GRADE: Grade C: Consensus,
      disease-oriented evidence, expert opinion.

PMID- 21093807
TI  - It is not clear whether commonly used radiographic markers in panoramic images
      possess predictive ability for determining the relationship between the inferior
      alveolar nerve and the mandibular third molar.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Diagnostic accuracy of panoramic
      radiography in determining relationship between inferior alveolar nerve and
      mandibular third molar. Atieh MA. J Oral Maxillofac Surg 2010;68:74-82. REVIEWER:
      Ann Wenzel, DDS, PhD, Dr Odont. PURPOSE/QUESTION: Are 3 commonly accepted
      radiographic signs in panoramic images indicative of a close relationship between
      the inferior alveolar nerve and the mandibular third molar? SOURCE OF FUNDING:
      Information not available. TYPE OF STUDY/DESIGN: Systematic review with meta
      analysis of data. LEVEL OF EVIDENCE: Level 2:Limited-quality patient-oriented
      evidence. STRENGTH OF RECOMMENDATION GRADE: Grade B:Inconsistent and limited
      quality patient-oriented evidence.

PMID- 21093808
TI  - Only a small percentage of patients experience persistent pain for more than 6
      months after root canal therapy.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Frequency of persistent tooth pain
      after root canal therapy: a systematic review and meta-analysis. Nixdorf DR,
      Moana-Filho EJ, Law AS, McGuire LA, Hodges JS, John MT. J Endod 2010;36(2):224
      30. REVIEWER: Analia Veitz Keenan, DDS. PURPOSE/QUESTION: The aim of the study
      was to assess the frequency of pain at 6 months or more in association with
      endodontically treated permanent teeth. SOURCE OF FUNDING: Information not
      available. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis. LEVEL OF
      EVIDENCE: Level 1: Good-quality patient-oriented evidence. STRENGTH OF THE
      RECOMMENDATION GRADE: Grade A: Consistent, good-quality patient-oriented
      evidence.

PMID- 21093809
TI  - Salivary glucose levels are unable to predict oral candidiasis or monitor
      diabetes.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Salivary glucose levels and oral
      candidal carriage in type II diabetics. Sashikumar R, Kannan R. Oral Surg Oral
      Med Oral Pathol Oral Radiol Endod 2010;109(5):706-11. REVIEWER: Wenche S.
      Borgnakke, DDS, MPH, PhD. PURPOSE/QUESTION: (1) What is the relationship between
      salivary glucose and oral candida carriage? and (2) Can salivary glucose levels
      be used to monitor diabetes control? SOURCE OF FUNDING: The Chennai Dental
      Research Foundation, India. TYPE OF STUDY/DESIGN: Cross-sectional LEVEL OF
      EVIDENCE: Level 2: Limited-quality, patient-oriented evidence. STRENGTH OF
      RECOMMENDATION GRADE: Not applicable.

PMID- 21093810
TI  - Dental caries prediction to target high-risk individuals in community-based
      preventive programs is problematic.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Life course dental caries
      determinants and predictors in children aged 12 years: a population-based birth
      cohort. Peres MA, Barros AJ, et al. Community Dent Oral Epidemiol 2009;37:123-33.
      REVIEWER: John P. Brown, BDS, MS, PhD. PURPOSE/QUESTION: To define selected life
      course social, biological, and behavioral exposures as determinants and
      predictors of dental caries in children at 12 years of age. SOURCE OF FUNDING:
      Brazilian National Council for Scientific and Technological Development CNPq
      Grant No. 403362/2004-0. TYPE OF STUDY/DESIGN: Cohort study. LEVEL OF EVIDENCE:
      Level 2: limited-quality patient-oriented evidence STRENGTH OF RECOMMENDATION
      GRADE: Not applicable.

PMID- 21093811
TI  - Hemostasis in periodontally treated patients on oral antithrombotic therapy may
      be possible.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Hemostatic management for
      periodontal treatments in patients on oral antithrombotic therapy: a
      retrospective study. Morimoto Y, Niwa H, Minematsu K. Oral Surg Oral Med Oral
      Pathol Oral Radiol Endod 2009;108(6):889-96. REVIEWER: Walter A. Bretz, DDS, PhD.
      PURPOSE/QUESTION: The authors attempted to evaluate hemostatic management of
      periodontal treatment in patients on oral antithrombotic therapy. SOURCE OF
      FUNDING: Information not available. TYPE OF STUDY/DESIGN: Retrospective case
      series LEVEL OF EVIDENCE: Level 3: Other evidence. STRENGTH OF RECOMMENDATION
      GRADE: Not applicable.

PMID- 21093812
TI  - Periodontal disease is related to local and systemic mediators of inflammation.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Local and systemic biomarkers in
      gingival crevicular fluid increase odds of periodontitis. Fitzsimmons TR, Sanders
      AE, Bartold PM, Slade GD. J Clin Periodontol 2010;37(1):30-6. REVIEWER: Ananda P.
      Dasanayake, BDS, MPH, PhD, FACE. PURPOSE/QUESTION: The authors attempted to study
      the independent and combined effects of local (IL-1beta) and systemic (CRP)
      inflammatory biomarkers in gingival crevicular fluid (GCF) on the risk of
      periodontitis. SOURCE OF FUNDING: Government: National Health and Medical
      Research Council (NHMRC) of Australia and NHMRC Sidney Sax Public Health
      Fellowship. TYPE OF STUDY/DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 2:
      Limited-quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not
      applicable.

PMID- 21093813
TI  - Interceptive orthodontic treatment improves malocclusions over no treatment, but
      does not produce finished-quality results.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Effectiveness of interceptive
      orthodontic treatment in reducing malocclusions. King GJ, Brudvik P. Am J Orthod
      Dentofacial Orthop 2010;137:18-25. REVIEWER: Anne-Marie Bollen, DDS, MS, PhD.
      PURPOSE/QUESTION: The purpose of this study was to investigate the effectiveness
      of interceptive treatment. SOURCE OF FUNDING: National Institute of Dental and
      Craniofacial Research (NIDCR grant #U54DE14254). TYPE OF STUDY/DESIGN: A
      retrospective cohort study. LEVEL OF EVIDENCE: Level 2: Limited-quality, patient
      oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable.

PMID- 21093814
TI  - Uncertainty remains regarding long-term success of mineral trioxide aggregate for
      direct pulp capping.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Mineral trioxide aggregate or
      calcium hydroxide direct pulp capping: an analysis of the clinical treatment
      outcome. Mente J, Geletneky B, Ohle M, Koch MJ, Friedrich Ding PG, Wolff D, et
      al. J Endod 2010;36(5):806-13. REVIEWER: Toru Naito, DDS, PhD. PURPOSE/QUESTION:
      To ascertain the long-term clinical success of direct pulp capping using mineral
      trioxide aggregate (MTA) versus using calcium hydroxide. SOURCE OF FUNDING:
      Information not available. TYPE OF STUDY/DESIGN: Retrospective cohort study.
      LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence. STRENGTH
      OF RECOMMENDATION GRADE: Not applicable.

PMID- 21093815
TI  - Tooth agenesis patterns in bilateral cleft lip/palate (BCLP) indicate possible
      common genetic pathways.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Tooth agenesis patterns in bilateral
      cleft lip and palate. Bartzela TN, Carels CEL, Bronkhorst EM, Ronning E, Rizell
      S, Kuijpers-Jagtman AM. Eur J Oral Sci 2010;118:47-52. REVIEWER: Michael D.
      Martin, DMD, MSD, MPH, MA, PhD. PURPOSE/QUESTION: Are there patterns of tooth
      agenesis in BCLP that may indicate genetic contributions common to tooth
      developmental anomalies and cleft lip/palate? SOURCE OF FUNDING: Supported by the
      Department of Dentistry, Radboud University Nijmegen Medical Center, the
      Netherlands. TYPE OF STUDY/DESIGN: Retrospective cohort. LEVEL OF EVIDENCE: Level
      2: Limited-quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE:
      Not applicable.

PMID- 21093816
TI  - Dentists consider medical screening important and are willing to incorporate
      screening procedures into dental practice.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Dentists' attitudes toward chairside
      screening for medical conditions. Greenberg BL, Glick M, Frantsve-Hawley J,
      Kantor ML. J Am Dent Assoc 2010;14(1):52-62. REVIEWER: Brian Laurence, DDS, PhD.
      PURPOSE/QUESTION: The purpose of the study was to obtain information about
      dentists' attitudes toward, acceptance of, and perceived barriers regarding
      screening for medical conditions in a dental setting. SOURCE OF FUNDING:
      Information not available. TYPE OF STUDY/DESIGN: Survey. LEVEL OF EVIDENCE: Level
      3: Other evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable.

PMID- 21093817
TI  - Periodontitis does not increase serum inflammatory markers IL-6 and CRP in solid
      organ transplant patients.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Periodontitis and inflammatory
      markers in transplant recipients. Shaqman M, Ioannidou E, Burleson J, Hull D,
      Dongari-Bagtzogou A. J Periodontol 2010;81(5):666-72. REVIEWER: Michael P.
      Rethman, DDS, MS. PURPOSE/QUESTION: Does the presence of severe chronic
      periodontitis or, alternately, individual signs of chronic periodontitis increase
      serum indicators of systemic inflammation among solid organ implant patients?
      SOURCE OF FUNDING: National Institute of Dental and Craniofacial Research (NIDCR
      grant #R21DE16466). TYPE OF STUDY/DESIGN: Cross-sectional study. LEVEL OF
      EVIDENCE: Level 2: Limited-quality, patient-oriented evidence. STRENGTH OF
      RECOMMENDATION GRADE: Not applicable.

PMID- 21093818
TI  - Individuals sustaining snowboarding and skiing accidents have different
      maxillofacial injury profiles.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Facial trauma: how dangerous are
      skiing and snowboarding?. Tuli T, Haechl O, Berger N, Laimer K, Jank S, Kloss F,
      Brandstatter A, Gassner R. J Oral Maxillofac Surg 2010;68(2):293-9. REVIEWER
      NAME: Mike T. John, DDS, MPH, PhD. PURPOSE/QUESTION: To compare the prevalence of
      maxillofacial injury types in individuals who sustained snowboarding and skiing
      accidents. SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN:
      Retrospective case series. LEVEL OF EVIDENCE: Level 2: Limited-quality, patient
      oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable.

PMID- 21093820
TI  - The first case of multidrug-resistant NDM-1-harboring Enterobacteriaceae in
      Taiwan: here comes the superbacteria!

PMID- 21093821
TI  - Investigating the vascular influences of sepsis in portal hypertension: better
      late than never?

PMID- 21093822
TI  - Application of serology in the diagnosis of Helicobacter pylori infection in
      patients with atrophic gastritis.

PMID- 21093823
TI  - Non-compressibility ratio of sonography in deep venous thrombosis.
AB  - BACKGROUND: The risk of post-thrombotic syndrome and pulmonary embolism can be
      increased if there is failure to diagnose deep venous thrombosis (DVT) promptly.
      Emergency physicians (EPs) need a quick and readily available test to diagnose,
      treat and help them decide whether to discharge or admit DVT patients in a timely
      manner. The aim of this study was to investigate the value of the non
      compressibility ratio of thrombosed veins in DVT patients, and give EPs an
      objective value to aid them in their decision-making with regard to DVT patients
      in the emergency department. METHODS: We reviewed 34 adult patients with DVT
      diagnosed by sonography in an emergency department. Medical records including
      demographic data and sonography results were retrospectively reviewed and
      analyzed. RESULTS: Mean age was 72.9 +/- 16.5 years. Group I comprised 14
      patients (41.2%) who had DVT in the popliteal and femoral veins. Group II
      comprised 8 patients (23.5%) who had DVT isolated to the popliteal vein and 12
      patients (35.3%) who had DVT isolated to the femoral vein. Group I had a
      significantly higher non-compressibility ratio than Group II (93.4 +/- 6.2% vs.
      80.1 +/- 19.2%, p < 0.05). The area under the receiver operating characteristic
      curve of the non-compressibility ratio between discriminating groups was 0.711
      (95% confidence interval, 0.527-0.854; p < 0.05). The clinical prognostic score
      of Group I was significantly higher than that of Group II (6.2 +/- 1.8 vs. 4.1 +/
      2.6, p < 0.05). There was a significant positive correlation between the non
      compressibility ratio of the thrombosed vein and the clinical prognostic score (p
      = 0.001). CONCLUSION: The non-compressibility ratio of the thrombosed vein
      provides EPs with an objective test to evaluate the severity of DVT and to admit
      patients for consideration of adverse outcomes.

PMID- 21093824
TI  - Comparison of transrectal ultrasound-guided biopsy of the prostate and
      transurethral resection of the prostate for detection of prostate cancer in
      patients with moderate lower urinary tract symptoms.
AB  - BACKGROUND: To compare transrectal ultrasound (TRUS)-guided biopsy of the
      prostate and transurethral resection of the prostate (TURP) for detection of
      prostate cancer (PCa) in patients with moderate lower urinary tract symptoms
      (LUTS) by retrospective chart review. METHODS: Between January 2004 and December
      2008, a total of 520 patients, aged 50.3-81.5 years, with moderate LUTS
      (International Prostate Symptom Score, 8-19), and elevation of prostate-specific
      antigen (>= 4 ng/mL), or abnormal findings by digital rectal examination, were
      enrolled for evaluation. All the patients were recommended to receive TRUS-guided
      biopsy of the prostate (TRUS biopsy group) or TURP (TURP group) due to the
      possibility of PCa, according to their choice after full explanation by the
      doctors. RESULTS: There were 379 patients in the TRUS biopsy group and 141 in the
      TURP group. PCa was detected in 80 patients (21.1%) in the TRUS group and in 27
      (19.1%) in the TURP group. Clinically localized PCa (T1-2N0M0) was found in 46
      patients (57.5%) in the TRUS biopsy group and in 16 (59.3%) in the TURP group.
      Bone metastasis was noticed in 22 (27.5%) patients in the TRUS biopsy group and
      in 7 (25.9%) in the TURP group. The percentage of low-grade tumor was
      significantly higher in the TURP group than in the TRUS biopsy group (11.1% vs.
      5%). CONCLUSION: TURP was not superior to TRUS-guided biopsy of the prostate for
      detection of PCa in patients with moderate LUTS and prostate-specific antigen >=
      4 ng/mL.

PMID- 21093825
TI  - Therapeutic effects of intra-articular botulinum neurotoxin in advanced knee
      osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a major cause of musculoskeletal pain that
      causes morbidity, physical limitation, and poor quality of life. The purpose of
      this study was to evaluate the therapeutic effects of intra-articular (IA)
      injection of botulinum neurotoxin A (BoNT/A) for advanced knee OA. METHODS:
      Twenty-four patients (38 knees) were enrolled, and the subjects were
      radiographically verified as having stage III or IV OA according to the Kellgren
      Lawrence classification. We used the Western Ontario and McMaster Universities
      Osteoarthritis Index to evaluate the therapeutic effects monthly for 6 months.
      BoNT/A (100 U) was reconstituted with 4.0 mL saline and was injected into the
      symptomatic knee joints after baseline evaluation and 3 months later. RESULTS:
      The therapeutic effects of BoNT/A were clinically significant at 1 month after
      the first injection, but statistical significance was not noted until 3 months
      after the first IA injection. Pain and stiffness improved clinically; however,
      the effect of BoNT/A achieved statistical significance only for the pain subscale
      in stage III OA. There was no significant difference between the stage III and IV
      groups. There was no significant muscle atrophy or serious adverse effect in any
      group after treatment. CONCLUSION: IA BoNT/A provides a new therapeutic option
      for refractory pain in patients with advanced knee OA. Although IA BoNT/A appears
      to be effective and safe for the management of advanced knee OA, these results
      cannot be generalized to patients with mild knee joint pain or nonspecific soft
      tissue pain in the knee joint region.

PMID- 21093826
TI  - Fatty acid composition of Taiwanese human milk.
AB  - BACKGROUND: The purpose of this study was to analyze quantitatively the fatty
      acid composition of the milk of Taiwanese women. METHODS: Two hundred and sixty
      nine human milk specimens were obtained from 240 Taiwanese mothers, aged 19-41
      years, and subjected to chromatographic analysis. RESULTS: Milk specimens were
      pooled by the mothers' districts of residence and lactation stages, at 0-11 days,
      22-45 days, 46-65 days and 66-297 days after delivery. The fatty acid composition
      was expressed as weight percentage of all fatty acids detected with C8-C24 chain
      length. More than 80% of the fatty acids were composed of lauric, myristic,
      palmitic, stearic, oleic and linoleic acids. The amount of saturated fatty acid
      was 36.7%. With regard to essential fatty acids, the amount of linoleic acid (LA)
      was 22% and that of linolenic acid (ALA) was 1.8%, both levels being higher than
      in human milk from Western countries. However, the ratio of LA/ALA remained at
      13:1 for the whole duration of lactation. It has been reported that mothers with
      high fish consumption have a high content of docosahexaenoic acid and
      eicosapentaenoic acid in their milk, and we found this phenomenon occurring in
      our study. The percentage of docosahexaenoic acid and eicosapentaenoic acid in
      Taiwanese human milk was 0.79% and 0.17%, respectively. CONCLUSION: Fatty acid
      composition in human milk varies during lactation. With regard to essential fatty
      acids, the amount of LA was 22% and that of ALA was 1.8%, both levels being
      higher than in human milk from Western and other Asian countries.

PMID- 21093827
TI  - Assessment of clinical competence of medical students using the objective
      structured clinical examination: first 2 years' experience in Taipei Veterans
      General Hospital.
AB  - BACKGROUND: Competence-oriented education is currently the mainstream method of
      teaching clinical medical education. The objective structured clinical
      examination (OSCE) is a widely employed and accepted tool to measure the clinical
      competence of medical students. We describe the first 2 years' experience of OSCE
      in Taipei Veterans General Hospital. METHODS: At Taipei Veterans General
      Hospital, every 7(th)-year medical student has taken the OSCE since 2006. There
      were 15 stations in the first 2 years' OSCEs. In years 1 and 2, 133 and 132
      students were assessed by the OSCE, respectively. The content of the OSCE
      included internal medicine, surgery, pediatrics, obstetrics and gynecology,
      communication, and emergency training. All categories and results of examinees'
      evaluation at each station were recorded inclusively and compared statistically.
      RESULTS: The average scores of students from the 15 stations ranged from 47.7 +/-
      16.4 to 93.7 +/- 8.5 in 2007. The score for communication skills was the lowest,
      whereas the score for Micro-Sim was the highest. Communication skills and
      electrocardiography interpretation were the 2 categories in which most of the
      students failed. A reliability analysis was conducted of the 2007 OSCE questions.
      The overall score and reliability (Cronbach's reliability) was 0.641. The
      difference between the impacts on reliability after deleting a test item ranged
      from 0.59 to 0.65 for all stations. This meant that every station had a similar
      impact on reliability after being deleted. The squared multiple correlation,
      R(2), of the reliability of each item was between 0.12 and 0.49, with chest X-ray
      interpretation being the lowest. The item-total correlation was between 0.10 and
      0.41, with interactive case being the lowest. CONCLUSION: The OSCE is an
      effective method for assessing the clinical competence of medical students. The
      OSCE could be improved further by modifying the examination questions and
      promoting effective training for standardized patients and examiners.

PMID- 21093828
TI  - First identification of a patient colonized with Klebsiella pneumoniae carrying
      blaNDM-1 in Taiwan.
AB  - New Delhi metallo-beta-lactamase 1 (NDM-1) is a novel type of metallo-beta
      lactamase (MBL). Enterobacteriaceae carrying this NDM-1 encoding gene, bla(NDM
      1), have been identified worldwide. Bacteria carrying bla(NDM-1) are not only
      resistant to carbapenem, but also highly resistant to many classes of
      antibiotics, which indicate the importance of prompt identification of these
      bacteria and implementation of strict infection control measures to prevent their
      transmission. Here, we report the first identification and management of a
      patient colonized with Klebsiella pneumoniae carrying bla(NDM-1) in Taiwan, who
      returned from New Delhi where he had been hospitalized for a gun-shot injury.

PMID- 21093829
TI  - Calcifying fibrous pseudotumor of the esophagus.
AB  - Calcifying fibrous pseudotumor is an uncommon lesion and has recently been
      recognized as a distinctive fibrous lesion. Esophageal calcifying fibrous
      pseudotumor is extremely rare and, to the best of our knowledge, has never been
      reported before. A 54-year-old woman underwent upper gastrointestinal endoscopy
      and endoscopic ultrasound because of intermittent dysphagia. The results showed 1
      isoechoic esophageal submucosal tumor over the deep mucosa and submucosal layers,
      with calcifications inside. The patient underwent tumor excision, and the
      diagnosis was confirmed by pathological features, with abundant collagen,
      calcification and inflammatory cell infiltration. She received regular follow-up
      at the clinic and no evidence of tumor recurrence was found.

PMID- 21093830
TI  - Invasive ductal carcinoma arising in phyllodes tumor with isolated tumor cells in
      sentinel lymph node.
AB  - Phyllodes tumor (PT) consists of stroma of variable grading and benign ductal
      epithelium. Although exceptional, carcinomas that arise from the epithelium in
      PTs do exist, and seem to behave less aggressively than the usually encountered
      breast carcinoma. To the best of our knowledge, among the invasive carcinomas
      that have arisen in PTs, only 1 has been proved to have metastatic carcinoma in
      the lymph nodes. Here, we describe the youngest woman to have invasive ductal
      carcinoma that arose in a borderline PT, with isolated carcinoma cells in the
      sentinel lymph node. Whether such a combined lesion carries a more indolent
      course is also discussed.

PMID- 21093831
TI  - Herpes zoster cervical myelitis in a young adult.
AB  - Varicella zoster virus infection, which causes chickenpox and herpes zoster (HZ),
      is not uncommon in the general population. Varicella zoster virus can be latent
      in cranial nerve or dorsal root ganglia, and reactivate several decades later to
      produce vesicles with post-herpetic neuralgia. HZ myelitis usually occurs in
      elderly or immunocompromised patients. We report here a case of HZ myelitis of
      the cervical spinal cord in a 35-year-old woman who was immunocompetent. Cervical
      myelitis developed 1 month after the eruption of vesicles. Pure sensation loss
      was limited initially from the C2 to T1 dermatomes, but later progressed to lower
      limb sensory loss and sphincter function impairment. The patient's motor function
      was also mildly affected. Despite the initial rapid neurological deterioration,
      the symptoms dramatically improved after 5 days of parenteral acyclovir and
      steroid administration with rehabilitation. We therefore propose that early
      medical intervention is necessary for better and earlier recovery.

PMID- 21093832
TI  - Focal nodular hyperplasia of the liver in a 5-year-old girl.
AB  - Focal nodular hyperplasia of the liver is a benign tumor that usually affects
      young women. Traditionally, its treatment in children has been conservative. As a
      result of its rarity in childhood, its differential diagnosis with other liver
      tumors is challenging. We present the case of a 5-year-old girl with a 1-week
      history of fever and abdominal pain. No definite diagnosis could be obtained
      after serial imaging and liver biopsy. As a result of uncertainty in the imaging
      and needle biopsy results, the patient underwent complete tumor resection.
      Pathology showed focal nodular hyperplasia that affected the right lobe of the
      liver. After surgery, the child was doing well at 24 months of follow-up.

PMID- 21093833
TI  - Developing physician leaders of patient-centered care.

PMID- 21093834
TI  - Dimensionality of measures for severe unilateral ankle arthritis.
AB  - OBJECTIVE: To analyze the dimensionality of 2 self-report outcome measures
      (Foot/Ankle Disability Index [FADI] and Short-Form [SF]-36), 3 biomechanical
      measures (stance and step symmetry measures, gait speed, and step width), 2
      physical-performance measures (timed get-up and go [TUG] and 4-square step test
      [4SST]), and 1 clinician-report outcome measure (American Orthopaedic Foot and
      Ankle Society [AOFAS] Hindfoot Scale) in a patient population with unilateral
      ankle arthritis. These measures captured the following functions: mobility and
      speed, pain and its relationship to function, social integration, and symmetry
      and efficiency of gait. DESIGN: Case series design. SETTING: Biomechanical
      research laboratory adjacent to a busy orthopedic clinical practice. PATIENTS:
      Seventy-nine consecutive patients with unilateral traumatic arthritis who were
      candidates for a total ankle replacement. METHODS: An exploratory factor analysis
      with oblimin rotation was performed to determine the dimensions of the physical
      performance, biomechanical, self-report, and clinician-report measures. MAIN
      OUTCOME MEASUREMENTS: Outcomes measures included the SF-36 and pertinent
      subscales, gait speed, the 4SST, the TUG, the FADI, the AOFAS Hindfoot Scale, and
      biomechanical measures of step width, step symmetry, and stance symmetry.
      RESULTS: Four distinct dimensions were captured during factor analysis. Factor 1
      included the TUG, gait speed, the 4SST, and step width; factor 2 included the
      FADI, the SF-36 bodily pain score, and the SF-36 physical function score; factor
      3 included the biomechanical scores of stance symmetry ratio and the step
      symmetry ratio; and factor 4 included SF-36 social functioning and the AOFAS
      Hindfoot Scale. CONCLUSIONS: Findings suggest that various outcome measures for
      the ankle capture different dimensions and should be considered when evaluating
      the presence of disability or long-term change in outcome.

PMID- 21093835
TI  - Spinal mobilization of postpartum low back and pelvic girdle pain: an evidence
      based clinical rule for predicting responders and nonresponders.
AB  - OBJECTIVE: To develop a clinical prediction rule (CPR) for identifying postpartum
      women with low back pain (LBP) and/or pelvic girdle pain (PGP) whose functional
      disability scores improve with a high-velocity thrust technique (HVTT) conducted
      by a physical therapist. DESIGN: Prospective cohort. SETTING: Outpatient physical
      therapy departments. PARTICIPANTS: Sixty-nine postpartum women referred to
      physical therapy with the complaint of LBP and/or PGP. METHODS: Subjects
      underwent a physical examination and a HVTT to the lumbopelvic region. MAIN
      OUTCOME MEASURES: Success with treatment was determined by the use of percent
      changes in disability scores and served as the reference standard for determining
      accuracy of the examination variables. Variables with univariate prediction of
      success and nonsuccess were combined into multivariate CPRs. RESULTS: Fifty-five
      subjects (80%) had success with the HVTT. A CPR for success with 4 criteria was
      identified. The presence of 2 of 4 criteria (positive likelihood ratio=3.05)
      increased the probability of success from 80% to 92%. A CPR for treatment failure
      with 3 criteria was identified. The presence of 2 of 3 criteria (positive
      likelihood ratio=11.79) increased the probability of treatment failure from 20%
      to 75%. CONCLUSIONS: The pretest probability of success (80%) is sufficient to
      reassure the clinician about the decision to use a HVTT to the lumbopelvic region
      in postpartum women with LBP and/or PGP. If 2 of 3 criteria for treatment failure
      are met in the CPR, an alternative approach is warranted. An intervention such as
      the HVTT is compelling, given the need to minimize pharmaceutical remedies in
      women who are potentially breast-feeding post partum.

PMID- 21093836
TI  - Characteristics and predictors of short-term outcomes in individuals self
      selecting yoga or physical therapy for treatment of chronic low back pain.
AB  - OBJECTIVE: To compare clinical and demographic characteristics of individuals
      self-selecting yoga or physical therapy (PT) for treatment of chronic low back
      pain (cLBP) and to examine predictors of short-term pain and functional outcomes.
      DESIGN: Descriptive, longitudinal study. SETTINGS: A hospital-based clinic that
      offers modified integral yoga classes for cLBP and 2 outpatient PT clinics that
      offer exercise-based PT. PARTICIPANTS: Adults (n=53) with cLBP>=12 weeks: yoga
      (n=27), PT (n=26). METHODS: Yoga participants attended a 6-week, once weekly, 2
      hour yoga class. PT participants underwent twice weekly, 1-hour individualized
      PT. Data were collected at baseline and at 6 weeks. Groups were compared by using
      chi2 and independent samples t-tests. Hierarchical linear regression was used to
      predict treatment outcomes. MAIN OUTCOME MEASURES: Disability (Roland Morris
      Disability Questionnaire), health status (Rand Short Form 36 Health Survey 1.0),
      pain bothersomeness (numerical rating scale), back pain self-efficacy (Back Pain
      Self-Efficacy Scale), and treatment satisfaction. RESULTS: At baseline, yoga
      participants were significantly less disabled (P=.013), had higher health status
      (P=.023), greater pain self-efficacy (P=.012), and less average pain
      bothersomeness (P=.001) compared with PT participants. At 6 weeks, when
      controlling for baseline group differences, greater pain self-efficacy was the
      strongest predictor for reduced pain and higher function for the entire sample. A
      significant group interaction by baseline pain self-efficacy predicted disability
      at 6 weeks. PT participants with low pain self-efficacy reported significantly
      greater disability than those with high pain self-efficacy. Yoga participants
      with low and high pain self-efficacy had similar disability outcomes. CONCLUSION:
      These findings strengthen evidence that self-efficacy is associated with cLBP
      outcomes, especially in individuals self-selecting PT. Further research to
      evaluate outcomes after yoga and PT in participants with low pain self-efficacy
      is needed.

PMID- 21093837
TI  - Are electrodiagnostic study findings related to a patient's response to epidural
      steroid injection?
AB  - OBJECTIVE: To determine if improvements in pain after epidural steroid injections
      (ESIs) were related to electromyographic (EMG) findings in patients with
      radicular symptoms and clinical findings consistent with radiculopathy. DESIGN:
      Retrospective chart review. SETTING: Multisite spine clinic. PATIENTS: Data were
      analyzed from 89 patients who had needle EMG within 6 months of ESI between 2005
      and 2008. METHODS: Clinical and demographic data and results of EMG testing from
      qualified patients were recorded from patient charts at least 10 days after ESI.
      Evidence of radiculopathy on EMG reports was classified as positive, normal, or
      equivocal. In all 3 EMG groups, the percentage of patients who had 50%
      improvement in leg pain after ESI was noted. As a secondary analysis, improvement
      in pre-ESI to post-ESI leg and back pain scores in the EMG groups were compared.
      OUTCOME MEASUREMENTS: The clinical outcome measurements were visual analog scale
      (VAS) scores assessing leg and back pain. ESI relief was defined as at least 50%
      improvement in the VAS score assessing leg pain after the injection. RESULTS: EMG
      findings were normal in 47.2%, positive in 31.5%, and equivocal in 21.3% of
      patients. No significant differences were found in the percentages of patients
      experiencing a positive response to the ESI with respect to EMG findings. Forty
      three percent of patients with normal EMG findings (18/42), 25.0% of patients
      with positive EMG findings (7/28), and 31.6% patients with equivocal EMG findings
      (6/19) had relief after ESI. In all 3 EMG groups, a statistically significant
      improvement in mean VAS scores was found after ESI. CONCLUSIONS: Mean leg and
      back pain scores improved significantly after ESI in all 3 EMG groups: those with
      positive, normal, and equivocal findings. Results of this study do not suggest
      that ESI is contraindicated in patients with normal EMG findings.

PMID- 21093838
TI  - Physical therapy workforce in the United States: forecasting nationwide
      shortages.
AB  - OBJECTIVE: To examine current and future physical therapy (PT) job
      surplus/shortage trends across the United States. DESIGN: Forecast models and
      grading methodology previously published for nursing were used to evaluate
      individual state PT job shortages from 2008 to 2030. SETTING: Not applicable.
      PARTICIPANTS: Not applicable. METHODS: The forecast model used to project PT job
      supply and demand accounted for changes in age and population size on the basis
      of estimates from the U.S. Census Bureau for each of the 50 states. PT shortages
      were assigned letter grades on the basis of shortage ratios (difference between
      demand and supply per 10,000 people) to evaluate PT shortages and describe the
      changing PT workforce in each state. RESULTS: On the basis of current trends,
      demand for PT services will outpace the supply of PTs within the United States.
      Shortages are expected to increase for all 50 states through 2030. By 2030, the
      number of states receiving below-average grades for their PT shortages will
      increase from 12 to 48. States in the Northeast are projected to have the
      smallest shortages, whereas states in the south and west are projected to have
      the largest shortages. CONCLUSION: These data serve to provide health
      professionals, policy makers, and stakeholders with a means of assessing current
      and future PT needs. Discussion of the issues surrounding PT shortages and
      ongoing assessment of supply and demand must ensue to mitigate projected
      shortages. Although our model has several limitations and may be oversimplified,
      it is the first attempt to use available, creditable data to examine both supply
      and demand for the entire country. Follow-up studies that use more complex
      modeling are needed to adequately forecast future trends beyond that accomplished
      in the current article. Monitoring trends over time is critical to maintain an
      appropriate balance between PT supply and demand that meets the population needs.

PMID- 21093840
TI  - Social media and health care: an overview.

PMID- 21093841
TI  - Point/Counterpoint. Posttraumatic stress disorder versus traumatic brain injury.

PMID- 21093842
TI  - Intramuscular infection: an unusual cause of back pain.

PMID- 21093839
TI  - The biopsycho-ecological paradigm: a foundational theory for medicine.
AB  - The current biomedical and psychosocial frameworks that form the conceptual basis
      of medicine today are insufficient to address the needs of the medically complex
      and environmentally challenged populations of patients often cared for by
      physical medicine and rehabilitation specialists. The expanded biopsycho
      ecological model of health, illness, injury, and disability operating through
      mechanisms of Health Environmental Integration (HEI) encourages a more complete
      understanding of illness, injury, activity limitation, and participation
      restriction as arising at the interface between the person and the environment.
      HEI recognizes complex interacting multilevel functional hierarchies beginning at
      the cellular level and ending at the individual's experience of the environment.
      Although the foci of illness and injury are within the body and mind, the
      physical and social environments contain elements that can cause or exacerbate
      disease and barriers that interact in ways that lead to injuries and
      disabilities. Furthermore, these environments hold the elements from which
      treating agents, facilitators, and social supports must be fashioned. The highly
      integrative biopsycho-ecological framework provides an expanded basis for
      understanding the objective causes and subjective meanings of disabilities.
      Disabilities are reduced through HEI by seeking to maximally integrate the body
      and mind (the self) with both the surrounding physical environment and other
      people in society. HEI offers mechanisms for interdisciplinary research, an
      expanded framework for education and empowerment, and a blueprint for optimizing
      day-to-day clinical care at both the individual patient and treatment population
      levels in the ever-changing scientific, political, and policy environments.

PMID- 21093843
TI  - Resolution of an intraspinal cyst associated with spondylolysis causing
      radiculopathy in an adolescent athlete: a case report.

PMID- 21093844
TI  - Elevation in the serum and urine concentration of injury-related molecules after
      the formation of deep tissue injury in a rat spinal cord injury pressure ulcer
      model.

PMID- 21093845
TI  - ["The neocricoid": A new surgical technique to prevent and treat tracheostomal
      stenosis after total infracricoid laryngectomy].
AB  - The goal is to present a new surgical technique that may solve and prevent
      tracheostomal stenosis after total infracricoid laryngectomy. The concepts on
      which the technique is based are explained and the technique as performed is
      described. The complete success achieved in three clinical cases treated with
      this technique is also presented.

PMID- 21093847
TI  - Development and validation of nomograms for predicting preterm delivery.
AB  - OBJECTIVE: The objective of the study was to develop a statistical model for
      predicting risk of preterm delivery after in utero transfer for threatened
      preterm delivery in tertiary care centers. STUDY DESIGN: This study was an
      observational study including a total of 906 patients transferred for threatened
      preterm delivery at Paule-de-Viguier and Croix-Rousse University Hospitals.
      Clinical and sonographic data from 1 series were used to construct logistic
      regression models for predicting preterm delivery and were validated on an
      independent series. An Internet-based tool was developed to facilitate the use of
      the nomograms. RESULTS: Based on multivariate analyses, 2 nomograms were built: 1
      to predict delivery within 48 hours after transfer and 1 to predict delivery
      before 32 weeks. Discrimination and calibration of the predictive models were
      good when applied to the validation set (concordance index 0.73 and 0.72,
      respectively). CONCLUSION: We developed and validated nomograms to predict the
      individual probability of preterm birth after transfer for threatened preterm
      delivery.

PMID- 21093846
TI  - Placental microRNA expression in pregnancies complicated by preeclampsia.
AB  - OBJECTIVE: The role of posttranscription regulation in preeclampsia is largely
      unknown. We investigated preeclampsia-related placental microRNA (miRNA)
      expression using microarray and confirmatory quantitative real-time polymerase
      chain reaction experiments. STUDY DESIGN: Placental expressions of characterized
      and novel miRNAs (1295 probes) were measured in samples collected from 20
      preeclampsia cases and 20 controls. Differential expression was evaluated using
      Student t test and fold change analyses. In pathway analysis, we examined
      functions/functional relationships of targets of differentially expressed miRNAs.
      RESULTS: Eight miRNAs were differentially expressed (1 up-regulated and 7 down
      regulated) among preeclampsia cases compared with controls. These included
      previously identified candidates (miR-210, miR-1, and a miRNA in the 14q32.31
      cluster region) and others that are novel (miR-584 and miR-34c-5p). These miRNAs
      target genes that participate in organ/system development (cardiovascular and
      reproductive system), immunologic dysfunction, cell adhesion, cell cycle, and
      signaling. CONCLUSION: Expression of miRNAs that target genes in diverse
      pathophysiological processes is altered in the setting of preeclampsia.

PMID- 21093848
TI  - Evaluation of force applied during deliveries complicated by shoulder dystocia
      using simulation.
AB  - OBJECTIVE: We sought to objectively evaluate the amount of force applied during
      deliveries complicated by shoulder dystocia among different providers. STUDY
      DESIGN: Providers who do deliveries at our institution were approached for
      participation. The simulation exercise used a childbirth mannequin that measures
      the amount of force the provider applies to the fetal head during delivery. The
      amount of force applied and information regarding the provider's level of
      experience, height, weight, and gender was recorded. This study was approved by
      the hospital institutional review board. RESULTS: A total of 47 providers
      participated. The mean force applied during each situation was not associated
      with the provider's experience, height, weight, or gender. CONCLUSION: Provider
      experience, gender, and body habitus were not associated with the amount of force
      applied during delivery. We found differences between family medicine and
      obstetrics/gynecology providers. In addition, a significant number of all
      providers (19/47, 40%) pulled >100 N.

PMID- 21093849
TI  - Cortisol and brain: beyond the hippocampus.

PMID- 21093852
TI  - Stereoisomeric separation of some flavanones using highly succinate-substituted
      alpha-cyclosophoro-octadecaoses as chiral additives in capillary electrophoresis.
AB  - alpha-Cyclosophoro-octadecaoses (alpha-C18), produced by Rhodobacter sphaeroides,
      are mostly homogeneous in size with 18 glucose units per ring as the predominant
      form. alpha-C18s are linked by beta-(1->4)-linkages and one alpha-(1->6)-linkage
      and are also known to be highly substituted by acetyl (0-2 per mol) and/or
      succinoyl groups (1-7 per mol). We isolated and purified alpha-C18 and
      successfully used it in capillary electrophoresis (CE) as a chiral additive for
      the separation of five flavanones and flavanone-7-O-glycosides, including
      naringenin, hesperetin, eriodictyol, homoeriodictyol, isosakuranetin, and
      hesperidin. Throughout the CE experiment with unsubstituted alpha-C18 (ualpha
      C18) obtained after alkaline treatment of the isolated alpha-C18, we found that
      successful chiral separation critically depends on the presence of succinate
      substituents attached to alpha-C18 in CE, suggesting that succinoylation of alpha
      C18 is decisive for effective stereoisomeric separation.

PMID- 21093851
TI  - Mirtazapine alters cue-associated methamphetamine seeking in rats.
AB  - BACKGROUND: Methamphetamine (METH) is a potent psychostimulant, repeated use of
      which can result in a substance abuse disorder. Withdrawn individuals are highly
      prone to relapse, which may be driven, at least in part, by a hyperresponsivity
      to METH-associated cues that can prompt METH-seeking. Clinically efficacious
      pharmacotherapies for METH abuse are critically needed. Mirtazapine (Remeron) is
      an atypical antidepressant that antagonizes activated norepinephrine(alpha)2,
      histamine1 serotonin (5-HT)2(A/C), and 5-HT3 receptors. This pharmacologic
      profile prompted our interest in its potential for preventing relapse to METH
      taking. This study tested the hypothesis that mirtazapine would attenuate METH
      seeking in rats trained to self-administer METH. METHODS: Rats were trained to
      self-administer METH in a lever-pressing operant task. The effect of mirtazapine
      on METH-seeking was determined by evaluating lever pressing in the presence of
      cues previously associated with METH, but in the absence of METH reinforcement.
      Two paradigms were used: cue reactivity, wherein rats do not undergo extinction
      training, and a cue-induced reinstatement paradigm after extinction. RESULTS:
      Mirtazapine (5.0 mg/kg) pretreatment reduced METH-seeking by ~ 50% in the first
      15 min of cue reactivity and cue-induced reinstatement testing. This mirtazapine
      dose did not significantly affect motor performance. CONCLUSIONS: This study
      revealed the overlapping nature of cue reactivity and cue-induced reinstatement
      procedures and provided preclinical evidence that mirtazapine can attenuate METH
      seeking behavior.

PMID- 21093854
TI  - Publisher's note. Negation, questions, and structure building in a homesign
      system.

PMID- 21093853
TI  - Integrating conceptual knowledge within and across representational modalities.
AB  - Research suggests that concepts are distributed across brain regions specialized
      for processing information from different sensorimotor modalities. Multimodal
      semantic models fall into one of two broad classes differentiated by the assumed
      hierarchy of convergence zones over which information is integrated. In shallow
      models, communication within- and between-modality is accomplished using either
      direct connectivity, or a central semantic hub. In deep models, modalities are
      connected via cascading integration sites with successively wider receptive
      fields. Four experiments provide the first direct behavioral tests of these
      models using speeded tasks involving feature inference and concept activation.
      Shallow models predict no within-modal versus cross-modal difference in either
      task, whereas deep models predict a within-modal advantage for feature inference,
      but a cross-modal advantage for concept activation. Experiments 1 and 2 used
      relatedness judgments to tap participants' knowledge of relations for within- and
      cross-modal feature pairs. Experiments 3 and 4 used a dual-feature verification
      task. The pattern of decision latencies across Experiments 1-4 is consistent with
      a deep integration hierarchy.

PMID- 21093855
TI  - Retroactive adjustment of perceived time.
AB  - Accurately timing acoustic events in dynamic scenes is fundamental to scene
      analysis. To detect events in busy scenes, listeners must often identify a change
      in the pattern of ongoing fluctuation, resulting in many ubiquitous events being
      detected later than when they occurred. This raises the question of how delayed
      detection time affects the manner in which such events are perceived relative to
      other events in the environment. To model these situations, we use sequences of
      tone-pips with a time-frequency pattern that changes from regular to random ('REG
      RAND') or vice versa ('RAND-REG'). REG-RAND transitions are detected rapidly, but
      the emergence of regularity cannot be established immediately, and thus RAND-REG
      transitions take significantly longer to detect. Using a temporal order judgment
      task, and a light-flash as a temporal marker, we demonstrate that listeners do
      not perceive the onset of RAND-REG transitions at the point of detection (~530 ms
      post transition), but automatically re-adjust their estimate ~300 ms closer to
      the nominal transition. These results demonstrate that the auditory system
      possesses mechanisms that survey the proximal history of an ongoing stimulus and
      automatically adjust perception to compensate for prolonged detection time,
      allowing listeners to build meaningful representations of the environment.

PMID- 21093856
TI  - Co-activation of syntax in bilingual language production.
AB  - We report four experiments that examined whether bilinguals' production of one
      language is affected by the syntactic properties of their other language. Greek
      English and English-Greek highly proficient fluent bilinguals produced sentence
      completions following subject nouns whose translation had either the same or
      different number. We manipulated whether participants produced completions in the
      same language as the subject (the source language; one-language production) or
      the other language (the non-source language; two-language production), and
      whether they used only one language or both languages within the experimental
      session. The results demonstrated that the grammar systems of both languages were
      activated during both one-language and two-language production. The effects of
      the non-source language were particularly enhanced in two-language utterances,
      when both languages were used in the experiment, and when it was the bilinguals'
      native language. We interpret our results in terms of a model of bilingual
      sentence production.

PMID- 21093857
TI  - Seafood intake and urine concentrations of total arsenic, dimethylarsinate and
      arsenobetaine in the US population.
AB  - BACKGROUND: Seafood is the main source of organic arsenic exposure
      (arsenobetaine, arsenosugars and arsenolipids) in the population. Arsenosugars
      and arsenolipids are metabolized to several species including dimethylarsinate
      (DMA). OBJECTIVE: Evaluate the association of seafood intake with spot urine
      arsenic concentrations in the 2003-2006 National Health Nutrition and Examination
      Survey (NHANES). METHODS: We studied 4276 participants >= 6 years. Total arsenic
      was measured using inductively coupled plasma dynamic reaction cell mass
      spectrometry (ICPMS). Urine DMA and arsenobetaine were measured by high
      performance liquid chromatography coupled with ICPMS. RESULTS: Participants
      reporting seafood in the past 24-h had higher urine concentrations of total
      arsenic (median 24.5 vs. 7.3 MUg/L), DMA (6.0 vs. 3.5 MUg/L), arsenobetaine (10.2
      vs. 0.9 MUg/L) and total arsenic minus arsenobetaine (11.0 vs. 5.5 MUg/L).
      Participants reporting seafood >= 2/wk vs. never during the past year had 2.3
      (95% confidence interval 1.9, 2.7), 1.4 (1.2, 1.6), 6.0 (4.6, 7.8) and 1.7 (1.4,
      2.0) times higher (p-trend <0.001) concentrations of total arsenic, DMA,
      arsenobetaine and total arsenic minus arsenobetaine, respectively. In
      participants without detectable arsenobetaine and in analyses adjusted for
      arsenobetaine, seafood consumption in the past year was not associated with total
      arsenic or DMA concentrations in urine. CONCLUSION: Seafood intake was a major
      determinant of increased urine concentrations of total arsenic, DMA,
      arsenobetaine and total arsenic minus arsenobetaine in the US population.
      Epidemiologic studies that use total arsenic, DMA, the sum of inorganic arsenic,
      methylarsonate and DMA, and total arsenic minus arsenobetaine as markers of
      inorganic arsenic exposure and/or metabolism need to address seafood intake.

PMID- 21093859
TI  - New trends in fixation of proximal humeral fractures: a review.
AB  - Surgical treatment of proximal humeral fractures continues to be a challenge
      especially in osteoporotic patients. Locking plates and intramedullary nails have
      been used with satisfactory results but the previous reported complications have
      not been substantially reduced. Most of the existing studies involve a small
      number of patients followed up for a rather short period of time. Since proximal
      humeral fractures constitute a heterogenous group of complex fractures in an even
      more heterogenous population, no single fixation method is a panacea. Choice of
      implant and method of fixation should be selected according to individual patient
      and fracture pattern characteristics based on clearly defined indications and
      contraindications. Based on the findings of the existing clinical studies the
      authors propose a treatment algorithm.

PMID- 21093858
TI  - Hormonal profile, the PROGINS polymorphism, and erectile dysfunction complaints:
      data from a population-based survey.
AB  - OBJECTIVE: To evaluate a potential association among the hormonal profile,
      PROGINS polymorphism, and erectile dysfunction (ED) complaints in a large
      population-based sample in Sao Paulo, Brazil. DESIGN: Population-based
      questionnaire study. SETTING: Interviews, sleep recording, and blood sample were
      conducted in a sleep institute. PATIENT(S): The total study participants included
      467 men. INTERVENTION(S): General information was obtained through interviews,
      and a blood sample was collected for hormone levels, DNA extraction, and PROGINS
      genotyping. MAIN OUTCOME MEASURE(S): The effect of progesterone and the PROGINS
      polymorphism on the risk of developing ED were measured by questionnaire and
      blood sample. RESULT(S): Progesterone, prolactin, testosterone, and estradiol
      levels did not differ between the genotype groups (T1/T1 and T1/T2+T2/T2). No
      significant genotypic or allelic differences were found between individuals with
      ED complaints and controls. Multivariate logistic regression analyses including
      age, body mass index, hypertension, diabetes, apnea-hypopnea index, and genetic
      ancestry estimation, as well as the PROGINS polymorphism, confirmed the lack of
      association between the T2 allele carriers and the risk of ED (odds ratio = 0.80;
      95% confidence interval = 0.40-1.62). CONCLUSION(S): This is the first study to
      demonstrate the genotypic and allelic frequencies of the PROGINS polymorphism in
      a large population-based sample of men. The results do not support a direct role
      for the PROGINS polymorphism in the risk of developing ED; however, further
      examination of other variants within PR gene will be necessary to completely rule
      out an effect.

PMID- 21093860
TI  - Evaluation of anti-atherosclerotic activities of PPAR-alpha, PPAR-gamma, and LXR
      agonists in hyperlipidemic atherosclerosis-susceptible F(1)B hamsters.
AB  - BACKGROUND: Fenofibrate, a PPAR-alpha agonist and rosiglitazone, a PPAR-gamma
      agonist, reduce triglycerides and fatty acids in humans and in animal disease
      models. The efficacy of PPAR-alpha agonists in mouse model of human
      atherosclerosis disease has shown mixed results, and efficacy of PPAR-gamma and
      liver X receptor (LXR) agonists has not been evaluated in cholesterol ester
      transfer protein (CETP) producing animal models. METHODS AND RESULTS: The
      efficacy of PPAR-alpha, PPAR-gamma and LXR agonists on lipid lowering and
      antiatherosclerotic activities was studied in atherosclerosis-susceptible F(1)B
      hamster that showed greater responsiveness to dietary fat and cholesterol (HFHC)
      diet and increased severity of atherosclerosis compared to Golden Syrian (GS)
      hamsters (aortic lesion 0.3% in GS vs 5% in F(1)B). F(1)B hamsters were fed HFHC
      diet and simultaneously treated with fenofibrate, rosiglitazone, and T0901317 (a
      pan LXR agonist) for 8 weeks. Fenofibrate lowered triglycerides and LDL-C by
      >80%, rosiglitazone did not significantly impact plasma lipid levels, and as
      expected, T0901317 increased triglycerides by 3-fold and HDL-C by 50%. The
      lesions in the aortic arch area as measured by en face method, decreased by 81%,
      38% and 35%, following fenofibrate, rosiglitazone, and T0901317 treatments,
      respectively. In F(1)B hamster regression model, fenofibrate decreased levels of
      triglycerides and LDL-C by >85%, and LDL-C by >70%, respectively, which resulted
      in ~50% regression of aortic lesions compared to vehicle treated group, and ~36%
      compared to baseline. CONCLUSIONS: These results demonstrate that: (a) F(1)B
      hamster is more sensitive to developing diet-induced hyperlipidemia and
      atherosclerosis; and (b) the greater antiatherosclerotic efficacy of fenofibrate
      occurred primarily via reductions in proatherogenic lipoproteins. Thus, PPAR
      alpha selective agonist shows a greater anti-atherosclerotic response compared to
      PPAR-gamma and LXR agonists in diet-induced atherosclerosis-susceptible F(1)B
      hamster.

PMID- 21093861
TI  - Pregnancy associated plasma protein-A as a marker for myocardial infarction and
      death in patients with stable coronary artery disease: a prognostic study within
      the CLARICOR Trial.
AB  - OBJECTIVE: Pregnancy associated plasma protein-A (PAPP-A) is a potential new
      marker for vulnerable plaques in the coronary arteries only examined in stable
      coronary disease (CAD) in patients undergoing coronary angiography. Here we
      address the prognostic value of serum PAPP-A in unselected stable CAD patients.
      METHOD: Blood samples were drawn at study entry. Serum PAPP-A values >=4mIU/L
      were considered elevated. Mortality and non-fatal myocardial infarction was
      prospectively registered. The primary outcome was the composite outcome of
      myocardial infarction and all-cause mortality, secondary outcomes were all-cause
      mortality and myocardial infarction. RESULTS: Patients (n=4243) were followed for
      a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly
      related to the composite outcome of myocardial infarction and death (HR 1.99, 95%
      CI 1.62-2.45, p<0.0005), all-cause mortality (HR 2.42, 1.92-3.06, p<0.0005), and
      myocardial infarction (HR 1.40, 1.01-1.94, p=0.046). After Holm's correction, the
      latter significance disappeared. After adjustment for risk factors and medication
      at entry, elevated PAPP-A remained significantly related to the composite outcome
      (HR 1.51, 1.22-1.86, p<0.0005) and all-cause mortality (HR 1.68, 1.32-2.13,
      p<0.0005). CONCLUSION: In patients with stable CAD elevated serum PAPP-A seems
      promising as aid in identifying patients at high risk for death.

PMID- 21093863
TI  - The effects of estrogen deficiency and bisphosphonate treatment on tissue
      mineralisation and stiffness in an ovine model of osteoporosis.
AB  - While much research has been dedicated to understanding osteoporosis, the nature
      of mineral distribution and the mechanical property variation in diseased bone is
      poorly understood. The current study aimed to determine the effect of estrogen
      deficiency and bisphosphonate therapy on bone tissue properties using an ovine
      model of osteoporosis. Skeletally mature animals (4+ years) were divided into an
      ovariectomy group (ovx, n=20) and a non treatment control group (control, n=20).
      A zoledronic acid treated group was also included in which animals were estrogen
      deficient for 20 months prior to receiving treatment (Zol, n=4). Half of the
      control and ovx groups were euthanized 12 or 31 months post-operatively and all
      Zol animals were euthanised at 31 months. Individual trabeculae were removed from
      the proximal femur and were analysed at specific locations across the width of
      the trabeculae. The mineral content was measured using quantitative backscatter
      electron imaging and the modulus was measured using nanoindentation. The spatial
      distribution of tissue modulus and mineral content in bone from ovariectomised
      animals was similar to control. However, ovariectomy significantly reduced the
      overall mineral content and tissue modulus relative to the control group after 12
      months. Interestingly, significant differences were not maintained 31 months post
      OVX. Treatment with zoledronic acid increased the mineral content and tissue
      modulus relative to both the ovariectomised and control groups. Zoledronic acid
      was also found to alter the mineral and modulus gradients normally associated
      with healthy bone tissue. The current study provides evidence that both estrogen
      deficiency and zoledronic acid therapy significantly alter mineral content and
      the mechanical properties of trabecular tissue.

PMID- 21093864
TI  - Elliptical contact of thin biphasic cartilage layers: exact solution for
      monotonic loading.
AB  - A three-dimensional unilateral contact problem for articular cartilage layers is
      considered in the framework of the biphasic cartilage model. The articular
      cartilages bonded to subchondral bones are modeled as biphasic materials
      consisting of a solid phase and a fluid phase. It is assumed that the subchondral
      bones are rigid and shaped like elliptic paraboloids. The obtained analytical
      solution is valid for monotonically increasing loading conditions.

PMID- 21093865
TI  - The natural frequency of the foot-surface cushion during the stance phase of
      running.
AB  - Researchers have reported on the stiffness of running in holistic terms, i.e. for
      the structures that are undergoing deformation as a whole rather than in terms of
      specific locations. This study aimed to estimate both the natural frequency and
      the viscous damping coefficient of the human foot-surface cushion, during the
      period between the heel strike and the mid-stance phase of running, using a
      purposely developed one degree-of-freedom inverted pendulum state space model of
      the leg. The model, which was validated via a comparison of measured and
      estimated ground reaction forces, incorporated a novel use of linearized and
      extended Kalman filter estimators. Investigation of the effect of variation of
      the natural frequency and/or the damping of the cushioning mechanism during
      running, using the said model, revealed the natural frequency of running on said
      foot-surface cushion, during the stance phase, to lie between 5 and 11 Hz. The
      "extended Kalman filter (EKF)" approach, that was used here for the first time to
      directly apply measured ground forces, may be widely applicable to the
      identification process of combined estimation of both unknown physiological state
      and mechanical characteristics of the environment in an inverse dynamic model.

PMID- 21093866
TI  - A nonlinear characteristic regime of biomembrane force probe.
AB  - A linear relation between stiffness and aspiration pressure is the basis for
      biomembrane force probe (BFP), a widely used technique to measure minuscule
      forces. Here we perform finite element simulations and semi-analytical modeling
      of the BFP operation to show that, at low aspiration pressures, there exists a
      characteristic regime in which the relation between stiffness and aspiration
      pressure is actually nonlinear. We find that this nonlinear characteristic regime
      arises from a transition in configuration of a partially aspirated biomembrane
      force probe under increasing aspiration pressure. We discuss both the conditions
      for the transition and the characteristics of the nonlinear characteristic
      regime, as well as its potential applications.

PMID- 21093867
TI  - Synthesis and evaluation of molecularly imprinted core-shell carbon nanotubes for
      the determination of triclosan in environmental water samples.
AB  - Synthetic core-shell molecularly imprinted polymers (MIPs) were prepared for the
      extraction of trace triclosan in environmental water samples. The synthesis
      process combined a surface molecular imprinting technique with a sol-gel process
      based on carbon nanotubes (CNTs) coated with silica. The morphology and structure
      of the products were characterized by transmission electron microscopy and
      Fourier transform infrared spectroscopy. The adsorption properties of the
      polymers were demonstrated by equilibrium rebinding experiments and Scatchard
      analysis. The prepared imprinted materials exhibited fast kinetics, high capacity
      and favorable selectivity. The process of synthesis was quite simple and
      different batches of MIPs and non-imprinted polymers (NIPs) showed good
      reproducibility in the template binding. The feasibility of determination of
      triclosan from real samples was testified using spiked river and lake water
      samples. The recoveries of river water and lake water samples were ranged from
      92.1 to 95.3% and 90.7 to 93.6%, respectively, when the environmental water
      samples were spiked with 0.1, 0.3, and 0.5 MUg L(-1) of TCS. In addition, the
      reusability of MIPs and NIPs without any deterioration in capacity was
      demonstrated for at least 10 repeated cycles.

PMID- 21093869
TI  - A zirconium based nanoparticle for significantly enhanced adsorption of arsenate:
      Synthesis, characterization and performance.
AB  - In this study, a zirconium nanoparticle sorbent for significantly enhanced
      adsorption of arsenate (As(V)) was successfully synthesized. The characterization
      of the zirconium nanoparticle sorbent and its adsorption behavior for arsenate
      were investigated. The HRTEM micrographs showed that the sorbent was nanoscale
      with particle sizes ranging from 60 to 90nm. The thermal gravimetric and
      elemental analyses indicated that the sorbent had a molecular formula of
      Zr(2)(OH)(6)SO(4).3H(2)O. The X-ray diffraction study revealed that the sorbent
      was amorphous. The potentiometric titration study demonstrated the surface charge
      density of the sorbent decreased with an increase in solution pH, and the pH of
      zero point charge of the sorbent was around 2.85. The kinetics study showed that
      most of the uptake took place in the first 6h, and the adsorption equilibrium was
      obtained within 12h. The optimal pH for As(V) adsorption was between 2.5 and 3.5.
      The Langmuir equation well described the adsorption isotherm; the maximum
      adsorption capacity of 256.4mg As/g was found at the optimal pH, better than most
      of sorbents available in the market. The presence of fluoride or nitrate did not
      obviously affect the adsorption of As(V) onto the sorbent; however, the existence
      of humic acid, phosphate or silicate in aqueous solution significantly reduced
      the uptake of As(V). The humic acid did not cause the reduction of the As(V). The
      FTIR and XPS spectroscopic analyses revealed that surface hydroxyl and sulfur
      containing groups played important roles in the adsorption.

PMID- 21093868
TI  - Determination of polycyclic aromatic hydrocarbons from ambient air particulate
      matter using a cold fiber solid phase microextraction gas chromatography-mass
      spectrometry method.
AB  - Polycyclic aromatic hydrocarbons (PAH) from ambient air particulate matter (PM)
      were analyzed by a new method that utilized direct immersion (DI) and cold fiber
      (CF) SPME-GC/MS. Experimental design was used to optimize the conditions of
      extraction by DI-CF-SPME with a 100MUm polydimethylsiloxane (PDMS) fiber. The
      optimal conditions included a 5min equilibration at 70 degrees C time in an
      ultrasonic bath with an extraction time of 60min. The optimized method was
      validated by the analysis of a NIST standard reference material (SRM), 1649b
      urban dust. The results obtained were in good agreement with certified values.
      PAH recoveries for reference materials were between 88 and 98%, with a relative
      standard deviation ranging from 5 to 17%. Detection limits (LOD) varied from 0.02
      to 1.16ng and the quantification limits (LOQ) varied from 0.05 to 3.86ng. The
      optimized and validated method was applied to the determination of PAH from real
      particulate matter (PM10) and total suspended particulate (TPS) samples collected
      on quartz fiber filters with high volume samplers.

PMID- 21093870
TI  - Abnormal atrial activation is common in patients with arrhythmogenic right
      ventricular cardiomyopathy.
AB  - INTRODUCTION: Structural right atrial abnormalities have been described in
      patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However,
      little is known about electrocardiographic signs of atrial involvement in ARVC
      because no systematic studies have been conducted. METHODS: P-wave-triggered
      signal-averaged orthogonal electrocardiogram from 40 ARVC patients (46 +/- 15
      years, 16 females) was compared with recordings from age- and sex-matched healthy
      control subjects for assessment of P-wave duration and morphology. P-wave
      morphology was classified with regard to the P-wave polarity in leads X, Y, and
      Z. RESULTS: P-wave duration was longer in patients (135 +/- 18 vs 124 +/- 12
      milliseconds; P = .003). Two typical P-wave morphologies were identified in the
      controls: positive in X and Y and negative (45%) or biphasic (55%) in Z. In
      patients with ARVC , typical P waves were seen in only 60%, whereas 15 patients
      (37%) had atypical P-wave positive in all 3 leads (P < .0001). The presence of
      atypical P waves in the ARVC group was not associated with the presence of either
      structural or functional right ventricular abnormality. CONCLUSIONS: Patients
      with ARVC commonly demonstrate deteriorated atrial activation expressed either as
      prolonged P-wave duration or abnormal P-wave morphology. The P-wave abnormalities
      were not secondary to right ventricular dilatation. These findings show that
      atrial involvement is common in ARVC and may represent yet another manifestation
      of the disease to be considered for inclusion in ARVC diagnostic workup.

PMID- 21093872
TI  - Displacement of the heart by diaphragm: is this heart alternating?
AB  - A-64-year-old man was admitted to the emergency department because of dyspnea.
      Twelve-lead ECG revealed alternating QRS complexes. In consequence of diagnostic
      tests, i.e., chest tomography showed eventration of the left diaphragm. In this
      case, we present an unusual case of electrical alternans due to diaphragmatic
      eventration.

PMID- 21093871
TI  - A new electrocardiogram marker to identify patients at low risk for ventricular
      tachyarrhythmias: sum magnitude of the absolute QRST integral.
AB  - OBJECTIVE: We proposed and tested a novel electrocardiogram marker of risk of
      ventricular arrhythmias (VAs). METHODS: Digital orthogonal electrocardiograms
      were recorded at rest before implantable cardioverter-defibrillator (ICD)
      implantation in 508 participants of a primary prevention ICDs prospective cohort
      study (mean +/- SD age, 60 +/- 12 years; 377 male [74%]). The sum magnitude of
      the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. A
      derivation cohort of 128 patients was used to define a cutoff; a validation
      cohort (n = 380) was used to test a predictive value. RESULTS: During a mean
      follow-up of 18 months, 58 patients received appropriate ICD therapies. The SAI
      QRST was lower in patients with VA (105.2 +/- 60.1 vs 138.4 +/- 85.7 mV ms, P =
      .002). In the Cox proportional hazards analysis, patients with SAI QRST not
      exceeding 145 mV ms had about 4-fold higher risk of VA (hazard ratio, 3.6; 95%
      confidence interval, 1.96-6.71; P < .0001) and a 6-fold higher risk of
      monomorphic ventricular tachycardia (hazard ratio, 6.58; 95% confidence interval,
      1.46-29.69; P = .014), whereas prediction of polymorphic ventricular tachycardia
      or ventricular fibrillation did not reach statistical significance. CONCLUSION:
      High SAI QRST is associated with low risk of sustained VA in patients with
      structural heart disease.

PMID- 21093873
TI  - Hyperglycemia and diabetes mellitus in children with pancreatitis.
AB  - OBJECTIVE: To assess the risk factors for developing hyperglycemia and diabetes
      mellitus (DM) in children with pancreatitis. STUDY DESIGN: Patients (from infants
      to age 21 years) hospitalized with acute pancreatitis (AP), acute recurrent
      pancreatitis (ARP), and chronic pancreatitis were studied retrospectively.
      Subjects with known DM or cystic fibrosis before presentation with pancreatitis
      were excluded. RESULTS: A total of 176 patients met the study criteria. Of these,
      140 had AP, 29 had ARP, and 7 had chronic pancreatitis. Severe pancreatitis was
      associated with hyperglycemia; 41% of the patients with hyperglycemia required
      insulin, and 8 patients (4.5%) developed DM requiring insulin by the time of
      discharge. These 8 patients with postpancreatitis DM were more likely to be
      overweight. Five of the 8 patients had a seizure disorder, and 4 had another
      comorbidity, such as mental retardation or cerebral palsy. Seven of the 8
      patients who developed DM had a single episode of AP, and one patient had ARP.
      CONCLUSIONS: Our findings indicate that hyperglycemia and DM can occur with
      pancreatitis. In some cases, postpancreatitis DM was associated with mental
      retardation, seizure disorder, and use of antiseizure medication. As opposed to
      adults who develop DM after chronic pancreatitis, children can develop DM due to
      a single episode of AP.

PMID- 21093874
TI  - Improvements in exercise performance after surgery for Ebstein anomaly.
AB  - OBJECTIVE: The purpose of this longitudinal study was to assess improvements in
      exercise performance and quality of life in patients with Ebstein anomaly after
      surgical intervention. METHODS: In 21 patients with Ebstein anomaly (between 6
      and 59 years of age; 16 female, 5 male) who underwent surgery for tricuspid
      regurgitation and, if present, closure of an interatrial shunt, a cardiopulmonary
      exercise test and a quality-of-life assessment by the Medical Outcomes Study 36
      item short form was performed prior to and 6 to 18 months after surgery. RESULTS:
      After surgery, peak oxygen uptake increased from 68.4% of predicted to 77.3% of
      predicted (P = .009), and ventilatory efficiency (VE/VCO(2) slope) improved from
      32.5 to 29.3 (P = .001). In 14 patients with additional interatrial shunt
      closure, oxygen saturation improved from 95% to 99% at rest (P = .003) and from
      88% to 99% under peak exercise (P = .003). Improvements in VE/VCO(2) slope were
      similar in patients who had undergone primary surgery (P = .005) or reoperation
      (P = .018). Increase in exercise capacity was also similar in both groups but
      failed significance in both (primary surgery, P = .064; reoperation, P = .063).
      There was no difference between tricuspid valve repair and replacement in the
      short-term follow-up. Self-estimated quality of life was fairly good prior to and
      after surgery. Only in the single question about health transition at follow-up
      did the patients confirm an improved situation after surgery. CONCLUSIONS:
      Patients with Ebstein anomaly and severe tricuspid regurgitation draw clinical
      benefit from surgical intervention as measured on exercise testing. This holds
      true for primary surgery and for reoperation.

PMID- 21093875
TI  - Calcification of allograft and stentless xenograft valves for right ventricular
      outflow tract reconstruction: an experimental study in adolescent sheep.
AB  - OBJECTIVE: Aortic homografts were compared with pulmonary homografts in the
      setting of right ventricular outflow tract reconstruction in adolescent sheep.
      Furthermore, clinically available stentless porcine and bovine xenografts were
      studied as an alternative to homografts. METHODS: In 51 adolescent sheep
      cryopreserved aortic and pulmonary (ovine) homografts, as well as 6 different
      types of clinically available stentless bioprostheses (Prima Plus, Toronto SPV,
      Toronto BiLinx, Freestyle, Pericarbon Stentless, and Contegra) were implanted in
      the pulmonary position. After 5 to 6 months, the valves were explanted and
      studied for structural valve degeneration by means of radiographic analysis,
      histology, and calcium content determination. RESULTS: Pulmonary homografts
      calcified significantly less than aortic homografts in the wall portion. Leaflet
      calcification was mild, hardly detectable on radiographic analysis, and
      comparable between aortic and pulmonary homografts. Stentless porcine xenografts
      showed severe calcification in the aortic wall portion, irrespective of the
      antimineralization treatment. Leaflet calcification was mild and in the range of
      that seen in homografts. Pannus formation was present but never induced leaflet
      retraction or cusp immobilization. Calcification was absent in the stentless
      Pericarbon valve implants, but all valves showed extensive pannus overgrowth,
      leaflet retraction, and cusp immobilization. The Contegra valves showed wall
      calcification, but the leaflets were completely free of calcification and pannus.
      CONCLUSIONS: For right ventricular outflow tract reconstruction, the pulmonary
      homograft remains the first choice. All xenografts result in either calcific
      degeneration or cusp immobilization.

PMID- 21093876
TI  - Three-dimensional template-based planning for transapical aortic valve
      implantation.

PMID- 21093877
TI  - Prospective European multicenter randomized trial of PleuraSeal for control of
      air leaks after elective pulmonary resection.
AB  - OBJECTIVES: We sought to evaluate the efficacy and safety of a synthetic
      bioresorbable pleural sealant (PleuraSeal; Covidien, Bedford, Mass) to treat air
      leaks after pulmonary resection. METHODS: Patients with air leaks after lung
      resection were randomized to treatment with pleural sealant on air leak sites
      after standard methods of lung closure or standard lung closure only. The primary
      outcome variable was the percentage of patients remaining air leak free until
      discharge. The secondary outcome variables were the proportion of patients with
      successful intraoperative air leak sealing, time to last air leak, and durations
      of chest tube drainage and hospitalization. RESULTS: The sealant group comprised
      62 subjects, and the control group comprised 59 subjects. Most patients (98.3%)
      underwent open lobectomy for bronchogenic carcinoma. The overall success rates
      for intraoperative air leak sealing were as follows: sealant group, 71.0%;
      control group, 23.7% (P < .001). For grade 2 and 3 air leaks (n = 77), the
      intraoperative sealing rates were as follows: sealant group, 71.7%; control
      group, 9.1% (P < .001). More patients with grade 2 and 3 air leaks had their
      leaks remain sealed in the sealant group (43.5% vs 15.2%, P = .013). The median
      time from skin closure to last observable air leak was 6 hours (sealant group)
      versus 42 hours (control group, P = .718). No treatment-related complications
      were reported. No differences in drainage or hospitalization were observed.
      CONCLUSIONS: In this multicenter study the pleural sealant was safe and effective
      treatment for intraoperative air leaks after lung resection. Significantly fewer
      patients with surgically relevant intraoperative air leaks had postoperative air
      leaks when the pleural sealant was applied.

PMID- 21093878
TI  - Overexpression of MACC1 mRNA in lung adenocarcinoma is associated with
      postoperative recurrence.
AB  - OBJECTIVE: The purpose of this study was to clarify the role and clinical
      significance of metastasis associated in colon cancer 1 in resected stage I non
      small cell lung cancers. METHODS: Tumor specimens were collected from 146
      consecutive patients who underwent a complete resection for stage I lung
      adenocarcinoma from 1998 to 2007 at the University of Occupational and
      Environmental Health. We analyzed the expression of metastasis associated in
      colon cancer 1 mRNA of primary lung adenocarcinomas by real-time reverse
      transcriptase-polymerase chain reaction. RESULTS: The average postoperative
      observation period was 49.4 months. Thirteen (8.9%) of 146 patients had
      recurrences after surgery. Overexpression of metastasis associated in colon
      cancer 1 mRNA was identified in 62 patients (42.5%). Metastasis associated in
      colon cancer 1 was overexpressed in 9 (69.2%) of 13 patients and 53 (39.9%) of
      133 patients with and without recurrence, respectively (P = .004). The median
      metastasis associated in colon cancer 1 copy number was 3.0 and 1.4 in patients
      with and without tumor recurrence, respectively. Metastasis associated in colon
      cancer 1 overexpression was associated with poorer disease-free survival
      according to the survival analysis (P = .033). CONCLUSIONS: Metastasis associated
      in colon cancer 1 gene overexpression may be a useful marker for predicting
      postoperative recurrence in patients with lung adenocarcinoma after surgery.

PMID- 21093881
TI  - Robotic repair of posterior mitral valve prolapse versus conventional approaches:
      potential realized.
AB  - OBJECTIVE: Robotic mitral valve repair is the least invasive approach to mitral
      valve repair, yet there are few data comparing its outcomes with those of
      conventional approaches. Therefore, we compared outcomes of robotic mitral valve
      repair with those of complete sternotomy, partial sternotomy, and right mini
      anterolateral thoracotomy. METHODS: From January 2006 to January 2009, 759
      patients with degenerative mitral valve disease and posterior leaflet prolapse
      underwent primary isolated mitral valve surgery by complete sternotomy (n = 114),
      partial sternotomy (n = 270), right mini-anterolateral thoracotomy (n = 114), or
      a robotic approach (n = 261). Outcomes were compared on an intent-to-treat basis
      using propensity-score matching. RESULTS: Mitral valve repair was achieved in all
      patients except 1 patient in the complete sternotomy group. In matched groups,
      median cardiopulmonary bypass time was 42 minutes longer for robotic than
      complete sternotomy, 39 minutes longer than partial sternotomy, and 11 minutes
      longer than right mini-anterolateral thoracotomy (P < .0001); median myocardial
      ischemic time was 26 minutes longer than complete sternotomy and partial
      sternotomy, and 16 minutes longer than right mini-anterolateral thoracotomy (P <
      .0001). Quality of mitral valve repair was similar among matched groups (P = .6,
      .2, and .1, respectively). There were no in-hospital deaths. Neurologic,
      pulmonary, and renal complications were similar among groups (P > .1). The
      robotic group had the lowest occurrences of atrial fibrillation and pleural
      effusion, contributing to the shortest hospital stay (median 4.2 days), 1.0, 1.6,
      and 0.9 days shorter than for complete sternotomy, partial sternotomy, and right
      mini-anterolateral thoracotomy (all P < .001), respectively. CONCLUSIONS: Robotic
      repair of posterior mitral valve leaflet prolapse is as safe and effective as
      conventional approaches. Technical complexity and longer operative times for
      robotic repair are compensated for by lesser invasiveness and shorter hospital
      stay.

PMID- 21093882
TI  - Short- and long-term outcomes of 1000 adult lung transplant recipients at a
      single center.
AB  - OBJECTIVE: Lung transplantation has become accepted therapy for end-stage
      pulmonary disease. The objective of this study was to review a single-institution
      experience of adult lung transplants. METHODS: We reviewed 1000 adult lung
      transplants that were performed at Washington University between July 1988 and
      January 2009. RESULTS: Transplants were performed for emphysema (52%), cystic
      fibrosis (18.2%), pulmonary fibrosis (16.1%), and pulmonary vascular disease
      (7.2%). Overall recipient age was 48 +/- 13 years with an increase from 43 +/- 12
      years (July 1988-November 1993) to 50 +/- 14 years (June 2005-January 2009).
      Overall incidence of primary graft dysfunction was 22.1%. Hospital mortality was
      higher for patients who had primary graft dysfunction (primary graft dysfunction,
      13.6%; no primary graft dysfunction, 4%; P < .001). Freedom from bronchiolitis
      obliterans syndrome was 84% at 1 year, 38.2% at 5 years, and 12.2% at 10 years.
      Survival at 1, 5, 10, and 15 years was 84%, 56.4%, 32.2%, and 17.8%,
      respectively. Five-year survival improved from 49.6% (July 1988-November 1993) to
      62.1% (October 2001-June 2005). Primary graft dysfunction was associated with
      lower survival at 1, 5, and 10 years (primary graft dysfunction: 72.8%, 43.9%,
      and 18.7%, respectively; no primary graft dysfunction: 87.1%, 59.8%, and 35.7%,
      respectively, P < .001) and lower rates of freedom from bronchiolitis obliterans
      syndrome (primary graft dysfunction: 78%, 27.5%, and 8.5%, respectively; no
      primary graft dysfunction: 85.4%, 40.7%, and 13.1%, respectively, P = .007).
      CONCLUSIONS: Five-year survival has improved over the study period, but long-term
      outcomes are limited by bronchiolitis obliterans syndrome. Primary graft
      dysfunction is associated with higher rates of bronchiolitis obliterans syndrome
      and impaired short- and long-term survival. A better understanding of primary
      graft dysfunction and bronchiolitis obliterans syndrome is critical to improve
      outcomes.

PMID- 21093883
TI  - Early microbial biofilm formation on marine plastic debris.
AB  - An important aspect of the global problem of plastic debris pollution is plastic
      buoyancy. There is some evidence that buoyancy is influenced by attached biofilms
      but as yet this is poorly understood. We submerged polyethylene plastic in
      seawater and sampled weekly for 3 weeks in order to study early stage processes.
      Microbial biofilms developed rapidly on the plastic and coincided with
      significant changes in the physicochemical properties of the plastic. Submerged
      plastic became less hydrophobic and more neutrally buoyant during the experiment.
      Bacteria readily colonised the plastic but there was no indication that plastic
      degrading microorganisms were present. This study contributes to improved
      understanding of the fate of plastic debris in the marine environment.

PMID- 21093884
TI  - Detection and phylogenetic analysis of an atypical pestivirus, strain IZSPLV_To.
AB  - Recently, atypical bovine pestiviruses (BVDV-3) have been identified in batches
      of contaminated foetal calf serum (FCS) and in naturally infected cattle. During
      routine screening of FCS by conventional panpestivirus PCR assay, one batch
      showed traces of pestivirus nucleic acids, and the contaminating virus was typed
      as BVDV-3-like. Phylogenetic analysis based on three genome regions (5'UTR,
      N(pro) and E2) showed that this strain, named IZSPLV_To, clusters in a separate
      clade with CH_KaHo/cont, a cell culture contaminant detected in Switzerland. This
      study is the first report of the detection in Italy of a FCS batch contaminated
      with BVDV-3 and adds more evidence that atypical pestiviruses represent a serious
      cause for concern in cell culture laboratories, with potential repercussions on
      BVD control and vaccine biosafety. Our findings suggest that the BE/B2 primers
      may be able to detect BVDV-3 in a panpestivirus assay, but testing of a larger
      number of strains is required.

PMID- 21093885
TI  - Review and update of involuntary facial movement disorders presenting in the
      ophthalmological setting.
AB  - We review the existing literature on the involuntary facial movement disorders
      benign essential blepharospasm, apraxia of eyelid opening, hemifacial spasm, and
      aberrant facial nerve regeneration. The etiology of idiopathic blepharospasm, a
      disorder of the central nervous system, and hemifacial spasm, a condition
      involving the facial nerve of the peripheral nervous system, is markedly
      different. We discuss established methods of managing patients and highlight new
      approaches.

PMID- 21093886
TI  - Sperm ultrastructure of a member of the black coral family Aphanipathidae:
      Rhipidipathes reticulata (Anthozoa, Antipatharia).
AB  - Fertile male polyps of three colonies of the black coral Rhipidipathes reticulata
      (Aphanipathidae) from Togian Islands (Indonesia) have been the source of the
      sperm investigated at ultrastructural level, in order to compare their
      organization with that of other members belonging to the family Antipathidae and
      Myriopathidae. The extension of the studies to a representative of the family
      Aphanipathidae stresses once more the structural similarity of the male gametes
      in antipatharians. A sketch of the sperm model reports the similarity and
      differences in the examined taxa. Among the micro-characters, the cup-like body
      linked to the pericentriolar apparatus, is exclusive of the antipatharians. Other
      inclusions concern the more common pro-acrosomal vesicles or the acrosomelike
      structure observed only in Antipathella subpinnata and Myriopathes japonica.
      Lipid vesicles are occasionally present. A typical inclusion, the electron-dense
      content of which has a C-shaped configuration, is restricted to Rhipidipathes
      reticulata and is associated to the cup-like body or to the mitochondrion.

PMID- 21093887
TI  - Degradation of the antibiotic amoxicillin by photo-Fenton process--chemical and
      toxicological assessment.
AB  - The influence of iron species on amoxicillin (AMX) degradation, intermediate
      products generated and toxicity during the photo-Fenton process using a solar
      simulator were evaluated in this work. The AMX degradation was favored in the
      presence of the potassium ferrioxalate complex (FeOx) when compared to FeSO(4).
      Total oxidation of AMX in the presence of FeOx was obtained after 5 min, while 15
      min were necessary using FeSO(4). The results obtained with Daphnia magna
      biossays showed that the toxicity decreased from 65 to 5% after 90 min of
      irradiation in the presence of FeSO(4). However, it increased again to a maximum
      of 100% after 150 min, what indicates the generation of more toxic intermediates
      than AMX, reaching 45% after 240 min. However, using FeOx, the inhibition of
      mobility varied between 100 and 70% during treatment, probably due to the
      presence of oxalate, which is toxic to the neonates. After 240 min, between 73
      and 81% TOC removal was observed. Different pathways of AMX degradation were
      suggested including the opening of the four-membered beta-lactamic ring and
      further oxidations of the methyl group to aldehyde and/or hydroxylation of the
      benzoic ring, generating other intermediates after bound cleavage between
      different atoms and further oxidation to carboxylates such acetate, oxalate and
      propionate, besides the generation of nitrate and ammonium.

PMID- 21093888
TI  - Reducing bromate formation with H(+)-form high silica zeolites during ozonation
      of bromide-containing water: Effectiveness and mechanisms.
AB  - This paper investigated the effect of H(+)-form high silica ZSM-5 (HZSM-5)
      zeolites on bromate formation. HZSM-5 zeolites with different Si/Al molar ratios
      (i.e., 25-300) were tested taking ozonation alone as control. The zeolites were
      more effective in reducing bromate formation for the filtered surface water than
      CeO2, a former reported oxide that can reduce bromate formation at slightly
      acidic pH. The reduction efficiencies were not closely related to their Si/Al
      ratios. The HZSM-5 (Si/Al=300) selected for detailed studies effectively reduced
      bromate formation by 58% for the filtered water, and also enhanced the removal of
      dissolved organic carbon (DOC) during ozonation. The efficiency of the HZSM-5 in
      reducing bromate formation increased with ozone dose (0.38-1.16 mg O3 mg-1 DOC)
      and pH (6.6-9.3). The HZSM-5 adsorbed OBr- (one of the critical intermediates in
      bromate formation) quickly with an adsorption capacity of 54 mg g-1, but had no
      adsorption for ozone, Br-, HOBr and BrO3-. It also significantly inhibited the
      formation of trace H2O2 which was generated from ozone decomposition and had been
      considered promoting bromate formation at low concentrations during ozonation.
      The reduction of bromate formation in O3/HZSM-5 is possibly ascribed to the
      selective OBr- adsorption in combination with the inhibited H2O2 formation.

PMID- 21093889
TI  - Scraper reduction and "imposed form" at the Lower Palaeolithic site of High
      Lodge, England.
AB  - This paper investigates patterns of scraper retouch at the Lower Palaeolithic
      site of High Lodge, England. The unifacial scrapers from High Lodge are
      intensively retouched tools with regular and complex shapes that have been
      routinely interpreted as evidence of intentional design. The primary aim is to
      determine whether the different scraper types identified in the assemblage
      represent discrete and discontinuous implement categories made according to fixed
      designs, or rather, points or stages along one or more reduction continuums. To
      achieve this, we apply a range of quantitative measures of artifact reduction to
      all complete single, double, convergent, and transverse scrapers from the site
      (n=165). Our results indicate that morphological and typological diversity in the
      High Lodge scraper assemblage can be parsimoniously explained as a result of both
      the extent to which implements were resharpened during use and subtle variability
      in the nature of blank forms selected for retouch. Accordingly, we critique the
      notion that high levels of morphological complexity in retouched Lower
      Palaeolithic tool types necessarily reflect the imposition of preconceived forms
      on stones.

PMID- 21093890
TI  - Historical biomonitoring of fluoride pollution by determining fluoride contents
      in roe deer (Capreolus capreolus L.) antlers and mandibles in the vicinity of the
      largest Slovene thermal power plant.
AB  - Roe deer antlers/mandibles are a useful tool for determination of ambient
      fluoride pollution. Antlers have a well-defined annual cycle of growth, therefore
      they represent a natural standardisation of samples during winter months. On the
      contrary, mandibles accumulate fluorides during the whole life of an organism,
      thus they reflect aggregated effect of fluoride pollution trough the life-span of
      an organism. Both tissues are easily available; mandibles are often
      systematically collected with the purpose of cognitive management and control,
      and antlers could be gathered from private well-dated hunters' collections.
      Considering these benefits, fluoride contents were measured in 141 antlers
      (period 1960-2007) and 220 mandibles (period 1997-2009) of roe deer, shot in the
      vicinity of the largest Slovene Thermal Power Plant of Sostanj (STPP) as one of
      the major sources of fluorides in Slovenia. Fluoride contents in antlers
      significantly differed among age categories, and ranged from 110 to 1210 mg/kg in
      yearlings, 130 to 2340 mg/kg in young adults, and 250 to 2590 mg/kg in older
      adults, respectively. Fluoride levels in mandibles were also significantly
      different among age categories, and ranged from 30.0 to 227 mg/kg in fawns, 33.8
      to 383 mg/kg in yearlings, and 61.5 to 1020 mg/kg in adults, respectively.
      Comparison of these results with previously reported fluoride contents in antlers
      and mandibles of roe deer from different areas of Europe revealed that the study
      area has never been extensively contaminated with fluorides. Moreover, trends of
      fluoride contents in both tissues confirmed a significant decrease of fluoride
      pollution in the area after the years 1995 and 2000, when flue-gas cleaning
      devices were constructed on the STPP. Indeed, highly positive correlations
      between annual emissions from the STPP and mean annual fluoride contents in
      antlers/mandibles confirmed that both tissues may be a useful tool for assessing
      temporal trends in ambient fluoride pollution.

PMID- 21093891
TI  - Factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase
      (MTHFR) C677T polymorphisms and the risk of tamoxifen-associated thromboembolism
      in breast cancer patients.

PMID- 21093892
TI  - Platelet transfusions: impact on hemostasis, thrombosis, inflammation and
      clinical outcomes.
AB  - Platelet transfusion is one of the most crucial therapeutic approaches in
      Medicine. However, severe and fatal adverse reactions may develop. In addition to
      their important function in hemostasis, platelets' role in inflammation has
      become more evident. Recently, platelets are also recognized as the main source
      of circulating soluble CD40 ligand (sCD40L, (CD154)), which plays significant
      roles in hemostasis, platelet activation, clot stability, interactions with other
      cells, and upregulation of different mediators. In this review, we will briefly
      highlight the importance of platelet transfusion, its role in inflammatory and
      thrombotic transfusion reactions, and visit the most recent findings on sCD40L.

PMID- 21093893
TI  - EORTC 55971: does it apply to all patients with advanced state ovarian cancer?

PMID- 21093894
TI  - MMP-1-PAR1 axis mediates LPA-induced epithelial ovarian cancer (EOC) invasion.
AB  - OBJECTIVES: MMP-1 is over-expressed in many cancers, with high expression often
      associated with poor survival. In the present study, we examined the expression
      of MMP-1 in EOC and its role in EOC invasion. Moreover, we evaluated the role of
      a newly identified MMP-1-protease activated receptor (PAR)-1 axis in LPA-induced
      EOC invasion. METHODS: MMP-1 and PAR1 mRNA expression in EOC cell lines was
      determined by real time PCR. MMP-1 mRNA expression in 96 normal and carcinoma
      ovarian tissue specimens was analyzed using a TissueScan real time PCR array. MMP
      1 concentration in conditioned medium was measured by MMP-1 ELISA. PAR1 protein
      expression was detected by Western blotting. Cell invasion was evaluated by in
      vitro Matrigel invasion assay. RESULTS: In ovarian tumor tissues more MMP-1
      expression was observed than in normal ovarian tissues (p<0.05), and its
      expression correlated with tumor grade (grade 3>grade 2>grade 1). Human
      recombinant MMP-1 as well as serum free conditioned medium containing high levels
      of MMP-1 from DOV13 and R182 cells significantly promoted DOV13 cell invasion
      (p<0.05), implicating a direct role of MMP-1 in EOC invasion. Moreover, MMP-1
      induced DOV13 invasion was significantly blocked by PAR1 siRNA silencing.
      Furthermore, MMP-1 and PAR1 were both significantly induced by LPA (20 MUM), and
      siRNA silencing of MMP-1 and PAR1 both significantly reduced LPA's invasion
      promoting effect in DOV13 cells (p<0.05). CONCLUSIONS: Our results suggest that
      the MMP-1-PAR1 axis is involved in EOC invasion and at least partially mediates
      LPA-induced EOC invasion. Therefore, blocking MMP-1 or PAR1 may represent a new
      therapeutic option for metastatic EOC.

PMID- 21093895
TI  - Endovaginal magnetic resonance imaging of stage 1A/1B cervical cancer with A T2-
      and diffusion-weighted magnetic resonance technique: effect of lesion size and
      previous cone biopsy on tumor detectability.
AB  - OBJECTIVE: To evaluate the effects of previous cone biopsy and lesion size on
      detectability of stage 1a/1b cervical cancer using endovaginal T2- and diffusion
      weighted magnetic resonance imaging. METHODS: One hundred and thirteen patients
      with cervical tumor were imaged using an endovaginal coil with T2-weighted (T2-W)
      and diffusion-weighted single-shot echo-planar sequences; 85 managed surgically
      (58 with prior cone biopsy/LLETZ) were evaluated. T2-W images and ADC maps viewed
      simultaneously were scored positive or negative for tumor and compared with
      histology at surgery. MRI tumor volumes, maximum radiological and histological
      dimensions were recorded. ROC analysis determined the MRI volume with optimal
      sensitivity/specificity for identifying tumor in those without and with prior
      cone biopsy/LLETZ and the maximum histological dimension for correctly
      identifying tumor with MRI. Mean apparent diffusion coefficients (ADCs) from
      tumor and adjacent normal epithelium were compared. RESULTS: Sensitivity and
      specificity for detecting tumor in those without (100%; 100% respectively) and
      with (80%; 78.9% respectively) prior cone biopsy/LLETZ were significantly
      different (p<0.001). Following cone biopsy/LLETZ, MRI tumor volume of 83 mm3
      detected tumor with 80% sensitivity, 94.7% specificity; a 5.3mm maximal
      histological dimension was detected on MRI with 100% sensitivity, 100%
      specificity. Tumor ADCs were significantly lower (p<0.001) than paired normal
      epithelial tissue (median, 988*10(-6) mm2/s vs. 1564*10(-6) mm2/s) but neither
      tumor nor epithelial ADCs differed significantly between patients with or without
      prior cone biopsy/LLETZ (p=0.48 and 0.15, respectively). CONCLUSIONS: Endovaginal
      MRI with T2- and diffusion-weighted sequences has significantly lower sensitivity
      and specificity for tumor detection following cone biopsy/LLETZ.

PMID- 21093896
TI  - ERCC1 (excision repair cross-complementation group 1) expression as a predictor
      for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer.
AB  - OBJECTIVE: Platinum-based neoadjuvant chemotherapy for locally advanced cervical
      cancer has some benefits for patients responding to chemotherapy. However, no
      validated clinical or biologic predictor of response to this chemotherapy has
      been identified to date. METHODS: We employ immunohistochemical analysis to
      determine the expression patterns of the excision repair cross-complementation
      group1 (ERCC1) protein in pre-treatment cervical biopsy tissue. In total, 43
      stage IIB patients had been enrolled in a previous etoposide and cisplatin
      neoadjuvant phase II clinical trial, allowing comparison of the effects of
      cisplatin-based neoadjuvant chemotherapy on response in relation to ERCC1
      expression. RESULTS: Among the 43 patients studied, 34 (79.1%) were positive and
      9 (20.9%) were negative for ERCC1. Response to chemotherapy (according to RECIST
      criteria) was observed in all patients with negative ERCC1 expression. In
      logistic regression analysis, ERCC1 negativity continued to be an independent
      predictor for responsiveness to neoadjuvant chemotherapy (p=0.021). Among the
      pretreatment factors, low ERCC1 expression was a significant prognostic factor of
      disease-free survival in multivariate analysis (p=0.046). CONCLUSIONS: The ERCC1
      expression patterns in pretreatment specimens may thus facilitate the prediction
      of responses to cisplatin-based NAC. We propose that patients expressing low
      levels of ERCC1 derive the most benefit from cisplatin-based NAC.

PMID- 21093897
TI  - Detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal
      lavages, a feasibility study.
AB  - OBJECTIVE: To explore the feasibility of DNA methylation analysis for the
      detection of cervical neoplasia in self-obtained cervico-vaginal lavages.
      METHODS: Lavages collected by a self-sampling device and paired cervical
      scrapings were obtained from 20 cervical cancer patients and 23 patients referred
      with an abnormal cervical smear (15 with high-grade cervical intraepithelial
      neoplasia (CIN2+) and 8 without CIN). All lavages and scrapings were analyzed by
      liquid based cytology (LBC), Hybrid Capture II (HC-II) for hr-HPV DNA detection
      and by DNA methylation analysis (JAM3, TERT, EPB41L3 and C13ORF18). Concordance
      between lavages and scrapings was measured by Cohen's Kappa (k). RESULTS: In
      lavages and scrapings from cervical cancer patients (n=20), methylation analysis
      was positive in 19 (95%) and 19 (95%), HC-II in 16 (80%) and 15 (75%) and LBC in
      15 (75%) and 19 (95%), respectively. In lavages and scrapings from CIN2+ patients
      (n=15), methylation analysis was positive in 10 (67%) and 12 (80%), HC-II in 15
      (100%) and 15 (100%) and LBC in 11 (73%) and 12 (80%), respectively. Concordance
      between cervical scrapings and lavages (n=43) was for LBC k=0.522 (p<0.001), hr
      HPV testing k=0.551 (p<0.001) and DNA methylation analysis k=0.653 (p<0.001).
      CONCLUSIONS: DNA methylation analysis in cervico-vaginal lavages obtained by a
      self-sampling device is feasible and its diagnostic performance appears to be at
      least comparable to the detection of cervical neoplasia by cytomorphology and hr
      HPV. Our pilot study suggests that detection of cervical neoplasia by DNA
      methylation analysis in cervico-vaginal lavages warrants exploration of its use
      in large prospective studies.

PMID- 21093898
TI  - Comparison of gene expression patterns between avian and human ovarian cancers.
AB  - OBJECTIVES: A putative model of spontaneous cancer has been described in the
      laying hen that bears significant similarities to human ovarian cancer. Our
      objective was to characterize and compare the patterns of gene expression in
      chicken and human forms of this disease. METHODS: RNA from 20 localized and
      metastatic ovarian and oviductal chicken tumor samples was isolated, amplified
      using in vitro transcription, and hybridized against normal ovarian epithelium to
      a customized cDNA microarray constructed for these studies. Differentially
      expressed genes were identified for localized ovarian, metastatic ovarian, and
      oviductal (or tubal) cancer by class comparison using BRB-ArrayTools. Results
      were validated with semi-quantitative PCR. A gene list (prediction model)
      constructed with the class prediction tool was used in a human ovarian cancer
      microarray obtained from the GEO datasets (GSE6008) in order to compare these
      results across species. RESULTS: Class comparison analysis between localized
      ovarian, metastatic ovarian and oviductal cancer yielded 41 different informative
      probes that coded for 27 unique genes. Localized ovarian samples clustered
      between metastatic ovarian and oviductal cancer samples. Using our chicken data
      as a training set and leaving oviductal samples out of the analysis, we created a
      prediction model that classified early stage and advanced stage human ovarian
      cancer gene expression arrays with 78% overall accuracy. CONCLUSIONS: Gene
      expression of spontaneous ovarian cancer in the chicken is comparable to gene
      expression patterns of human ovarian cancer.

PMID- 21093900
TI  - Hypersensitivity to systemic corticosteroids: an infrequent but potentially life
      threatening condition.

PMID- 21093899
TI  - Endometrial cancer and genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2
      within a population-based case-control study.
AB  - OBJECTIVE: We assessed whether common genetic variation in PTEN, PIK3CA, AKT1,
      MLH1, and MSH2-genes that reportedly are frequently altered in endometrial cancer
      was associated with risk of endometrial cancer. METHODS: Using data from a
      population-based case-control study in Poland (PECS) of 417 cases and 407 matched
      controls, we genotyped 76 tagging single nucleotide polymorphisms (tagSNPs;
      located in or within 10 kb upstream or 5 kb downstream of the gene of interest,
      minor allele frequency >=5% among various ethnic groups, and not already
      represented by another tagSNP at a LD of r(2) >=0.80) on an Illumina Custom
      Infinium iSelect assay that included over 29,000 SNPs in 1316 genes. For
      individual SNPs, we used unconditional logistic regression models, adjusted for
      age and site, to generate odds ratios (ORs) and 95% confidence intervals (CIs).
      To replicate the one statistically significant association in PECS, we
      independently genotyped that tagSNP among 1141 endometrial cancer cases and 2275
      controls from the SEARCH study in the UK. We assessed haplotypes via extended
      haplotype blocks and the sequential haplotype scan method. RESULTS: The rs2677764
      tagSNP in PIK3CA was statistically significantly associated with endometrial
      cancer in PECS (OR=1.42, 95% CI, 1.03-1.95; P=0.03) but not SEARCH (OR=0.98, 95%
      CI=0.82-1.17). Of the 25 haplotypes observed in at least 5% of cases and controls
      in PECS, only 1, in PIK3CA, was statistically significantly associated with
      endometrial cancer (OR=1.39, 95% CI, 1.00-1.93). All haplotype global p-values
      were null. CONCLUSION: Common genetic variation in PTEN, PIK3CA, AKT1, MLH1, or
      MSH2 was not statistically significantly associated with endometrial cancer.

PMID- 21093902
TI  - Value-based medicine pricing: NICE work?

PMID- 21093901
TI  - Corrosion behavior of Ti-5Ag alloy with and without thermal oxidation in
      artificial saliva solution.
AB  - OBJECTIVES: The aim of the present study was to investigate the effect of thermal
      oxidation on the corrosion behavior of Ti-5Ag alloy. METHODS: The microstructure
      of Ti-5Ag alloy without and with thermal oxidization treatment were
      characterized, with commercial pure (CP) Ti as control, by means of X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning electron
      microscopy (SEM). The electrochemical behavior in artificial saliva solution was
      compared for CP Ti, Ti-5Ag alloy with and without thermal oxidation. RESULTS:
      Compared to CP Ti, Ti-5Ag alloy without thermal oxidization treatment possessed
      much lower current density, higher open circuit potential, larger impedance
      value, and its corrosion resistance could be further improved with thermal
      oxidation. SIGNIFICANCE: The corrosion resistance was enhanced by Ag addition for
      titanium and could be further improved by thermal oxidation.

PMID- 21093903
TI  - Intensified glucose control in type 2 diabetes--whose agenda?

PMID- 21093904
TI  - The health of prisoners.
AB  - More than 10 million people are incarcerated worldwide; this number has increased
      by about a million in the past decade. Mental disorders and infectious diseases
      are more common in prisoners than in the general population. High rates of
      suicide within prison and increased mortality from all causes on release have
      been documented in many countries. The contribution of prisons to illness is
      unknown, although shortcomings in treatment and aftercare provision contribute to
      adverse outcomes. Research has highlighted that women, prisoners aged 55 years
      and older, and juveniles present with higher rates of many disorders than do
      other prisoners. The contribution of initiatives to improve the health of
      prisoners by reducing the burden of infectious and chronic diseases, suicide,
      other causes of premature mortality and violence, and counteracting the cycle of
      reoffending should be further examined.

PMID- 21093905
TI  - Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in
      intravenously exposed mice.
AB  - Mesoporous hollow silica nanoparticles (MHSNs) are emerging as one of the new and
      promising nanomaterials for biomedical applications, but the biocompatibility of
      MHSNs in vivo has received little attention. In the present study, the systematic
      single and repeated dose toxicity, biodistribution and clearance of MHSNs in vivo
      were demonstrated after intravenous injection in mice. For single dose toxicity,
      lethal dose 50 (LD(50)) of 110 nm MHSNs was higher than 1000 mg/kg. Further
      repeated dose toxicity studies indicated no death was observed when mice were
      exposed to MHSNs at 20, 40 and 80 mg/kg by continuous intravenous administration
      for 14 days. These results suggest low toxicity of MHSNs when intravenous
      injection at single dose or repeated administrations. ICP-OES and TEM results
      show that the MHSNs mainly accumulate in mononuclear phagocytic cells in liver
      and spleen. In addition, these particles could be excreted from the body and the
      entire clearance time of the particles should be over 4 weeks. These findings
      would be useful for future development of nanotechnology-based drug delivery
      system and other biomedical applications.

PMID- 21093906
TI  - Hydrophilic surface coatings with embedded biocidal silver nanoparticles and
      sodium heparin for central venous catheters.
AB  - Central venous catheters (CVCs) have become indispensable in the treatment of
      neonates and patients undergoing chemotherapy or hemodialysis. A CVC provides
      easy access to the patient's circulation, thus enabling facile monitoring of
      hemodynamic parameters, nutritional support, or administration of (cytostatic)
      medication. However, complications with CVCs, such as bacterial bloodstream
      infection or thromboembolism, are common. Bloodstream infections, predominantly
      caused by Staphylococcus aureus, are notoriously difficult to prevent and treat.
      Furthermore, patients receiving infusion therapy through a CVC are at risk for
      deep-vein thrombosis, especially of the upper limbs. Several recent clinical
      trials have shown that prophylactic anticoagulation (low-molecular-weight heparin
      or vitamin K antagonists) is not effective. Here, we report on the systematic
      development of a new bifunctional coating concept that can -uniquely- be applied
      to make CVC surfaces antimicrobial and antithrombogenic at the same time. The
      novel coating consists of a moderately hydrophilic synthetic copolymer of N
      vinylpyrrollidinone (NVP) and n-butyl methacrylate (BMA), containing embedded
      silver nanoparticles (AgNPs) and sodium heparin. The work demonstrates that the
      AgNPs strongly inhibit adhesion of S. aureus (reference strain and clinical
      isolates). Surprisingly, heparin not only rendered our surfaces practically non
      thrombogenic, but also contributed synergistically to their biocidal activity.

PMID- 21093907
TI  - The influence of biological motifs and dynamic mechanical stimulation in hydrogel
      scaffold systems on the phenotype of chondrocytes.
AB  - Primary bovine chondrocytes and PEG-based hydrogels were used to investigate the
      effects of scaffold composition and architecture on the cellular response to
      large dynamic compressive strain stimulation. Proteins and proteoglycans were
      conjugated to functionalized poly(ethylene glycol) (PEG) and immobilized in PEG
      hydrogels to create bio-synthetic scaffolds. Second passage articular
      chondrocytes were encapsulated into four different scaffold compositions: PEG
      Proteoglycan (PP), PEG-Fibrinogen (PF), PEG-Albumin (PA), and PEG only and
      subjected to 15% dynamic compressive strain at 1-Hz frequency. Cellular response
      was evaluated in terms of cell number, glycosaminoglycans (GAGs), collagen type
      II and collagen type I accumulation in the constructs following 24h and 28 days
      of stimulated and static culture. Stimulation of the constructs resulted in an
      increase in the cell number in all scaffolds, with no statistical difference
      measured among them. Dynamic stimulation of PP, PF, PA and PEG constructs
      resulted in a respective increase in the GAGs by 33%, 53.4%, 240.5%, and 284.5%,
      compared to their static controls. The permissive PEG and PA scaffolds showed a
      significantly larger relative increase in the GAGs in comparison to the other
      scaffolds tested. Collagen type II content in the PF, PA and PEG constructs
      increased by 78%, 1266% and 896% respectively, compared to their static controls.
      Permissive constructs showed a significantly larger relative increase and final
      absolute values of GAGs and type II collagen, compared to the PF constructs.
      Immunostaining for collagen type I, an indicator for chondrocyte de
      differentiation, indicated that stimulation inhibited its production. Correlation
      maps between scaffold properties highlighted the major differences between
      permissive and instructive scaffolds. These results support the hypothesis that
      both compressive strain and scaffold bioactivity have an important effect on the
      chondrocyte metabolic response to mechanical stimulation, and that the 3-D
      environment surrounding chondrocytes can actively participate in translating
      mechanical stimulation to the resident cells.

PMID- 21093908
TI  - Long-term in vitro human pancreatic islet culture using three-dimensional
      microfabricated scaffolds.
AB  - Human pancreatic islet in vitro culture is very challenging and requires the
      presence of various extra cellular matrix (ECM) components in a three-dimensional
      environment, which provides mechanical and biological support. The development of
      such an environment is vital in providing favourable conditions to preserve human
      islets in long-term culture. In this study, we investigated the effects of human
      islet culture within various three-dimensional environments; collagen I gel,
      collagen I gel supplemented with ECM components fibronectin and collagen IV, and
      microfabricated scaffold with ECM-supplemented gel. The cultured human islets
      were analyzed for functionality, gene expression and hormone content following
      long-term in vitro culture. It was clear the incorporation of ECM components
      within the three-dimensional support improved prolonged culture. However, long
      term and highly uniform human islet culture within a microfabricated scaffold,
      with controlled pore structures, coupled with the presence of ECM components,
      displayed an insulin release profile similar to freshly isolated islets, yielding
      a stimulation index of approximately 1.8. Moreover, gene expression was markedly
      increased for all pancreatic genes, giving a approximately 50-fold elevation of
      insulin gene expression with respect to suspension culture. The distribution and
      presence of pancreatic hormones was also highly elevated. These findings provide
      a platform for the long-term maintenance and preservation of human pancreatic
      islets in vitro.

PMID- 21093909
TI  - Direct and indirect effects of functionalised fluorescence-labelled nanoparticles
      on human osteoclast formation and activity.
AB  - Recently, it was demonstrated that phosphonate-functionalised nanoparticles were
      successfully taken up by mesenchymal stem cells without influencing their
      viability and differentiation capacity, suggesting that they may provide a
      promising basis for the development of nanoparticles for drug delivery or cell
      labelling. The present study aimed to investigate the effects of these
      nanoparticles on osteoclast formation and activity as well as on the inflammatory
      response of osteoclasts and osteoblasts. The intracellular uptake of the
      particles by human osteoclasts and osteoblasts was demonstrated by confocal laser
      scanning microscopy, transmission electron microscopy and fluorescence
      microscopy. The expression of tartrate-resistant acid phosphatase, carboanhydrase
      II, cathepsin K, calcitonin receptor and osteoclast-specific vacuolar proton pump
      subunit TCIRG1 as well as actin ring formation were not significantly altered in
      osteoclasts by particle treatment, as demonstrated by cytochemical staining and
      immunostaining. Active calcium phosphate resorption by osteoclasts was also not
      significantly influenced by the particles. The expression and secretion of pro
      inflammatory cytokines (IL-6, IL-1beta) by osteoclasts and osteoblasts and the
      expression of osteoclast-regulating genes (M-CSF, OPG, RANKL) in osteoblasts were
      similarly not significantly affected. In conclusion, phosphonate-functionalised
      nanoparticles did not affect osteoclast formation and activity either directly or
      indirectly, suggesting that they could provide a promising tool for the
      development of particle-based treatments for anti-resorptive therapies.

PMID- 21093910
TI  - Corticotrophin-releasing factor and urocortin inhibit system A activity in term
      human placental villous explants.
AB  - Plasma corticotrophin-releasing factor (CRF) and urocortin are elevated in
      preterm labour and/or fetal growth restriction (FGR). FGR is associated with
      reduced placental system A amino acid transporter activity and in vitro data
      suggest altered endocrine status could be responsible. Here we test the
      hypothesis that CRF and urocortin inhibit placental system A activity. Chronic
      (48h) exposure of term placental villous explants to these hormones (10(-7)M)
      significantly reduced system A activity (Na(+)-dependent (14)C
      methylaminoisobutyric acid uptake), whereas 1h exposure had no effect. We propose
      elevated CRF and urocortin contribute to FGR through negative regulation of
      placental system A activity.

PMID- 21093911
TI  - The synergistic effect of panobinostat (LBH589) with melphalan or doxorubicin on
      multiple myeloma cells; rationale for the use of combination regimens in myeloma
      patients.

PMID- 21093912
TI  - Cadmium and mercury-induced hyperglycemia in the fresh water crab, Oziotelphusa
      senex senex: involvement of neuroendocrine system.
AB  - The effect of exposure to sublethal concentrations of cadmium chloride and
      mercuric chloride on hemolymph glucose levels of the freshwater crab,
      Oziotelphusa senex senex, was studied. Intact crabs exposed to cadmium or mercury
      exhibited a significant hyperglycemia compared to controls, but no significant
      differences in hemolymph glucose level were detected among the eyestalkless crabs
      after exposure to metals, suggesting that the effect of metals could be on the
      sinus gland in the eyestalks, increasing secretion of the hyperglycemic hormone.
      To test this hypothesis, eyestalks were collected from control and metal exposed
      crabs, and tested for hyperglycemic effect and also for the hyperglycemic hormone
      levels. The levels of hyperglycemic hormone and the hyperglycemic effect were
      significantly low in the eyestalks collected from metal exposed crabs when
      compared with eyestalks from control crabs. These results strongly suggest that
      metals act, at least in part, by triggering the secretion of hyperglycemic
      hormone from the eyestalk.

PMID- 21093913
TI  - Dietary exposure of great blue heron (Ardea herodias) to PCDD/DFs in the
      Tittabawassee River floodplain, MI, USA.
AB  - Concentrations of dioxin-like compounds, primarily polychlorinated dibenzofurans
      (PCDFs), in soils and sediments of the Tittabawassee River (TR) and associated
      floodplains downstream of Midland, Michigan (USA) were greater than upstream
      sites and prompted a site-specific risk assessment of great blue herons (GBH).
      Dietary exposure of GBH to PCDFs and polychlorinated dibenzo-p-dioxins (PCDDs)
      was evaluated based on site-specific concentrations of residues in prey items.
      Concentrations of ?PCDD/DFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents
      (TEQ(WHO-Avian)) in prey items collected from the TR were consistently greater
      than those collected from associated reference areas (RAs) and further downstream
      in the Saginaw River (SR). The average daily dose (ADD(pot)) of ?PCDD/DFs to GBH
      was 45- to 54-fold greater along the TR and 12-fold greater along the SR when
      compared to the RA. ?PCDD/DFs were normalized to TEQ(WHO-Avian), and fold
      differences in the ADD(pot) increased, being 150- to 190-fold greater along the
      TR and 36-fold greater along the SR than they were in the RA. Greater fold
      changes in the ADD(pot) based on TEQ(WHO-Avian) between the RA and the TR and SR
      was due to prey items from the latter reaches having a greater relative toxic
      potency of ?PCDD/DFs, primarily from greater amounts of 2,3,7,8
      tetrachlorodibenzofuran but also 2,3,4,7,8-pentachlorodibenzofuran. Potential for
      adverse population-level effects from site-specific contaminant exposures were
      evaluated via comparison to selected toxicity reference values. The prediction of
      minimal to no risk of adverse population-level effects resultant from the
      assessment of site-specific dietary exposure of GBH to ?PCDD/DFs along the TR and
      SR is consistent with site-specific assessments of tissue-based exposures as well
      as population condition.

PMID- 21093914
TI  - Degeneration of the Arnold's prefrontopontocerebellar tract in a case of locked
      in syndrome over a 23-year period.
AB  - A 52-year-old woman has been under observation for a complete locked-in syndrome
      of vascular origin, since 1984. Her cognitive functions today are still normal.
      When first diagnosed, a CT-scan was made and 23 years later performed, a cerebral
      MRI was performed. A focal, bilateral and symmetric atrophy of the dorsomedial
      prefrontal gyri was clearly shown, contrasting with the non-atrophy of the
      precentral gyri (motor area), others prefrontal areas, frontopolar gyri and
      temporal cortices. Degeneration of the corticopontine projection, the first step
      in the corticopontocerebellar circuit, could explain this selective atrophy. This
      unique observation leads to the precise in vivo anatomical location of the Arnold
      tract. 

PMID- 21093915
TI  - Primary dural lymphoma with vault involvement mimicking meningioma.

PMID- 21093916
TI  - Repeated MR-based intravenous thrombolysis in a patient with short interval
      stroke recurrences.

PMID- 21093917
TI  - Spinal cervical metastasis from a glioblastoma multiform treated by percutaneous
      vertebroplasty: a case report.

PMID- 21093918
TI  - Advanced MRI in Rosai-Dorfman disease: correlation with histopathology.
AB  - Rosai-Dorfman disease is an idiopathic benign lymphoproliferative disorder that
      can, on rare occasions, cause intracranial or intraspinal lesions with non
      specific features on conventional imaging. For this reason, its diagnosis is
      based on the classical pathological findings of histiocyte proliferation and
      emperipolesis. In this case report, we describe the imaging features of Rosai
      Dorfman disease as visualized by newer types of MRI sequences, such as diffusion
      tensor imaging (DTI), susceptibility-weighted imaging (SWI) and perfusion
      weighted imaging (PWI). In fact, combining the findings of conventional cross
      sectional imaging with high fractional anisotropy (FA), a low apparent diffusion
      coefficient (ADC), mild blooming on SWI and decreased perfusion can help to make
      the diagnosis of Rosai-Dorfman disease. These newer tools can also be used to
      clarify the pathology of Rosai-Dorfman disease. 

PMID- 21093920
TI  - Evaluation of retinal nerve fiber layer progression in glaucoma: a comparison
      between the fast and the regular retinal nerve fiber layer scans.
AB  - OBJECTIVE: To compare the performance of the fast (256 A-scans in each scan
      circle) and the regular (512 A-scans in each scan circle) retinal nerve fiber
      layer (RNFL) scan protocols for detection of glaucoma progression using the
      Stratus optical coherence tomography (OCT) device (Carl Zeiss Meditec, Dublin,
      CA). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: One hundred twenty
      nine eyes from 72 glaucoma patients. METHODS: All patients had been followed up
      for 2.9 to 6.1 years with a median follow-up of 4 months. All eyes had at least 4
      serial RNFL measurements obtained with both the fast and the regular RNFL scans.
      Visual field (VF) assessment was performed on the same day as RNFL imaging.
      Retinal nerve fiber layer thickness and VF progression were evaluated with linear
      regression analysis against age. The mean rate of average RNFL thickness
      reduction was estimated with linear mixed modeling. MAIN OUTCOME MEASURES: The
      agreement of progression detection and the rate of change of RNFL thicknesses.
      RESULTS: A total of 1373 fast and 1373 regular RNFL scans and 1236 VF tests were
      analyzed. With reference to the average RNFL thickness, the fast RNFL scan
      detected more eyes with progression (21 eyes from 19 patients vs. 15 eyes from 13
      patients) than the regular scan at a comparable level of specificity (96.9% vs.
      96.1%). More eyes were found to have increasing RNFL thickness with age at
      individual clock hours (except for 3, 5, 6, and 11 o'clock) when the measurements
      were obtained with the regular scan. The agreement between the fast and the
      regular scan for detection of RNFL progression was fair to moderate, with kappa
      values ranging between 0.14 and 0.49. The rate of average RNFL thickness
      progression was -1.01 MUm per year for the fast RNFL scan and -0.77 MUm per year
      for the regular scan. CONCLUSIONS: The choice of scan protocols in the Stratus
      OCT has a significant impact in the evaluation of RNFL progression. The fast RNFL
      scan seems to be preferable to follow RNFL damage in glaucoma.

PMID- 21093919
TI  - Studies of the H60a locus in C57BL/6 and 129/Sv mouse strains identify the H60a
      3'UTR as a regulator of H60a expression.
AB  - The minor histocompatibility antigen 60 (H60a) is expressed in BALB/C and 129/Sv
      but not in C57BL/6 strains of mice. We recently found that IFNgamma down
      regulates H60a, but the mechanism of regulation is not known. To better
      understand the regulation of H60a, we examined the genomic locus of H60a in
      129/Sv and C57BL/6 strains. We found that the upstream regulatory region of H60a
      was present and functional in both strains. Interestingly, IFNgamma can down
      regulate H60a transcripts in cell lines from 129/Sv but not C57BL/6 strains of
      mice, suggesting that IFNgamma-dependent regulation of H60a proceeds through cis
      elements other than the conserved promoter region. We determined that the
      regulation of H60a by IFNgamma proceeds through the 3'UTR of H60a, which is
      present in 129/Sv, but not C57BL/6 cells. We also found that the H60a 3'UTR and
      microRNAs can contribute to the level of constitutive expression of H60a in tumor
      cell lines. We conclude that in 129/Sv strain mice, H60a can be regulated by its
      3'UTR through IFNgamma and unknown microRNAs. Since H60a mediates NK cell target
      recognition, our studies identify a cis element that can regulate virus and tumor
      surveillance.

PMID- 21093921
TI  - A standardized grading system for scleritis.
AB  - OBJECTIVE: This study evaluated the performance of a standardized grading system
      for scleritis using standard digital photographs. DESIGN: Cross-sectional
      interobserver agreement study. PARTICIPANTS: Photo archives from the National Eye
      Institute. METHODS: Three uveitis specialists from 3 different centers graded 79
      randomly arranged images of the sclera with various degrees of inflammation.
      Grading was done using standard screen resolution (1024*768 pixels) on a 0 to 4+
      scale in 2 sessions: (1) without using reference photographs and (2) with
      reference to a set of standard photographs (proposed grading system). The graders
      were masked to the order of images, and the order of images was randomized.
      Interobserver agreement in grading the severity of inflammation with and without
      the use of grading system was evaluated. MAIN OUTCOME MEASURES: Interobserver
      agreement. RESULTS: The proposed grading system for assessing activity in
      scleritis demonstrated a good interobserver agreement. Interobserver agreement
      (pooled kappa) was poor (0.289) without photographic guidance and improved
      substantially when the "grading system" with standardized photographs was used
      (kappa = 0.603). CONCLUSIONS: This system of standardized images for scleritis
      grading provides significantly more consistent grading of scleral inflammation in
      this study and has clear applications in clinical settings and clinical research.

PMID- 21093922
TI  - Effect of preoperative pupil size on quality of vision after wavefront-guided
      LASIK.
AB  - PURPOSE: To evaluate the effect of preoperative pupil size on quality of vision
      after wavefront-guided LASIK. DESIGN: Prospective study. PARTICIPANTS: One
      hundred two eyes. INTERVENTION: LASIK for mild to moderate myopia or astigmatism
      (preoperative manifest spherical equivalent, -3.99+/-1.42 diopters). MAIN OUTCOME
      MEASURES: Questionnaires evaluating specific visual symptoms before and after
      surgery. Each eye was evaluated before surgery, and 1 week and 1, 3, 6, and 12
      months postoperatively. Pupils were stratified according to size: small (<=5.5
      mm), medium (5.6-6.4 mm), or large (>=6.5 mm). Mesopic pupil size and
      preoperative and postoperative variables were evaluated using an analysis of
      variance. A regression model was also performed to determine the correlation
      between mean spherical equivalent and cylinder and visual symptoms. RESULTS: In
      the early postoperative period, there was no difference between the 3 groups with
      regard to any of the symptoms. At the final 12-month postoperative visit,
      patients with medium pupils experienced less glare at night than small pupils (P
      = 0.02), medium pupils had less halos than small or large pupils (P = 0.001 and P
      = 0.02, respectively), and medium pupils experienced greater satisfaction in
      visual improvement than small pupils (P = 0.014). CONCLUSIONS: Twelve months
      after wavefront-guided LASIK surgery, large pupil size does not positively
      correlate with any postoperative visual symptoms.

PMID- 21093923
TI  - Documentation of intraretinal retinal pigment epithelium migration via high-speed
      ultrahigh-resolution optical coherence tomography.
AB  - PURPOSE: To describe the features of intraretinal retinal pigment epithelium
      (RPE) migration documented on a prototype spectral-domain, high-speed, ultrahigh
      resolution optical coherence tomography (OCT) device in a group of patients with
      early to intermediate dry age-related macular degeneration (AMD) and to correlate
      intraretinal RPE migration on OCT to RPE pigment clumping on fundus photographs.
      DESIGN: Retrospective, noncomparative, noninterventional case series.
      PARTICIPANTS: Fifty-five eyes of 44 patients seen at the New England Eye Center
      between December 2007 and June 2008 with early to intermediate dry AMD. METHODS:
      Three-dimensional OCT scan sets from all patients were analyzed for the presence
      of intraretinal RPE migration, defined as small discreet hyperreflective and
      highly backscattering lesions within the neurosensory retina. Fundus photographs
      also were analyzed to determine the presence of RPE pigment clumping, defined as
      black, often spiculated, areas of pigment clumping within the macula. The en face
      OCT images were correlated with fundus photographs to demonstrate correspondence
      of intraretinal RPE migration on OCT and RPE clumping on fundus photography. MAIN
      OUTCOME MEASURES: Drusen, dry AMD, intraretinal RPE migration, and RPE pigment
      clumping. RESULTS: On OCT scans, 54.5% of eyes (61.4% of patients) demonstrated
      intraretinal RPE migration. Of the fundus photographs, 56.4% demonstrated RPE
      pigment clumping. All eyes with intraretinal RPE migration on OCT had
      corresponding RPE pigment clumping on fundus photographs. The RPE pigment
      migrated most frequently into the outer nuclear layer (66.7% of eyes) and less
      frequently into more anterior retinal layers. Intraretinal RPE migration mainly
      occurred above areas of drusen (73.3% of eyes). CONCLUSIONS: The appearance of
      intraretinal RPE migration on OCT is a common occurrence in early to intermediate
      dry AMD, occurring in 54.5% of eyes, or 61.4% of patients. The area of
      intraretinal RPE migration on OCT always correlated to areas of pigment clumping
      on fundus photography. Conversely, all but 1 eye with RPE pigment clumping on
      fundus photography also had areas of intraretinal RPE migration on OCT. The high
      incidence of intraretinal RPE migration observed above areas of drusen suggests
      that drusen may play physical and catalytic roles in facilitating intraretinal
      RPE migration in dry AMD patients.

PMID- 21093924
TI  - Blink lagophthalmos and dry eye keratopathy in patients with non-facial palsy:
      clinical features and management with upper eyelid loading.
AB  - PURPOSE: To evaluate the outcome of using upper eyelid gold weight implantation
      for patients with non-paralytic lagophthalmos on blink (LOB) only. We highlight
      the features of incomplete blink and reduced blink rate in patients with non
      facial palsy as an exacerbating factor in dry eye keratopathy. DESIGN:
      Retrospective, noncomparative case series. PARTICIPANTS: Twelve patients (21
      procedures) who underwent upper eyelid gold weight implantation for non-paralytic
      LOB only. METHODS: Retrospective case note review of patients who underwent upper
      eyelid loading for non-paralytic LOB only over a 5-year period at a single
      institution. MAIN OUTCOME MEASURES: Improvement in LOB, gentle and forced
      closure, increased frequency of blinking (FOB), degree of corneal staining,
      incidence of epithelial defects or corneal ulcer, improvement in vision, and
      subjective improvement in ocular discomfort. RESULTS: Twenty-one procedures in 12
      patients. Nine patients underwent bilateral surgery. Mean age was 56 (range, 8
      80) years. Median postoperative follow-up was 15 months, and mean follow-up was
      20.38 +/- 16.61 (6-58) months. Eleven of 12 patients had an improvement in LOB
      and increased FOB, resulting in improvement of keratopathy and reduced ocular
      discomfort. One patient developed superior corneal thinning and descemetocele,
      requiring removal of the gold weight; 1 patient required ptosis surgery; and 1
      patient developed a gold allergy and underwent platinum chain exchange.
      CONCLUSIONS: We highlight the need to consider incomplete blink and reduced FOB
      as exacerbating factors for corneal-related disorders, including dry eye. Upper
      eyelid loading with gold weight implantation is a useful and predictive method of
      improving exposure-related keratopathy due to LOB in the absence of facial palsy.

PMID- 21093925
TI  - Mindfulness-based cognitive therapy vs cognitive behaviour therapy as a treatment
      for non-melancholic depression.
AB  - AIM: To examine the comparative effectiveness of Mindfulness-Based Cognitive
      Therapy (MBCT) and Cognitive Behaviour Therapy (CBT) as treatments for non
      melancholic depression. METHOD: Participants who met criteria for a current
      episode of major depressive disorder were randomly assigned to either an 8-week
      MBCT (n=19) or CBT (n=26) group therapy condition. They were assessed at pre
      treatment, 8-week post-group, and 6- and 12-month follow-ups. RESULTS: There were
      significant improvements in pre- to post-group depression and anxiety scores in
      both treatment conditions and no significant differences between the two
      treatment conditions. However, significant differences were found when
      participants in the two treatment conditions were dichotomized into those with a
      history of four or more episodes of depression vs those with less than four. In
      the CBT condition, participants with four or more previous episodes of depression
      demonstrated greater improvements in depression than those with less than four
      previous episodes. No such differences were found in the MBCT treatment
      condition. No significant differences in depression or anxiety were found between
      the two treatment conditions at 6- and 12-month follow-ups. LIMITATIONS: Small
      sample sizes in each treatment condition, especially at follow-up. CONCLUSIONS:
      MBCT appears to be as effective as CBT in the treatment of current depression.
      However, CBT participants with four or more previous episodes of depression
      derived greater benefits at 8-week post-treatment than those with less than four
      episodes.

PMID- 21093926
TI  - Increased pituitary-adrenal activation and shortened gestation in a sample of
      depressed pregnant women: a pilot study.
AB  - BACKGROUND: Major depression (MD) is frequently accompanied by a relatively
      increased production of the stress hormone cortisol. During pregnancy
      corticotrophin releasing hormone (CRH) is secreted from the placenta and
      critically high levels of CRH are one of the key triggers for parturition.
      Maternal cortisol promotes the secretion of placental CRH. In this study, we
      examined the hypothesis that women suffering with MD in pregnancy would have
      relatively increased cortisol secretion, a time-advanced rise in placental CRH
      production and an earlier delivery of the baby. METHODS: A group of medication
      free pregnant women, free of know obstetric and medical complications, with
      (n=27) and without (n=38) MD were recruited. Blood concentrations of CRH,
      adrenocorticotrophic hormone (ACTH) and diurnal salivary cortisol concentrations
      were measured at fixed time points. RESULTS: Maternal cortisol concentrations
      were highly correlated with placental CRH secretion for the entire group. Second
      trimester CRH concentrations and mean evening salivary cortisol concentrations
      were significantly higher in the depressed women. Although pregnancy length was
      shorter in the depressed women there were no statistical relationships between
      the stress hormone measures and pregnancy length. LIMITATIONS: The sample size
      was small and highly selected. CONCLUSIONS: These findings suggest that depressed
      pregnant women hypersecrete cortisol in a diurnal pattern similar to that typical
      of MD, and that this leads to a time-advanced rise in placental CRH secretion.
      Factors other than this stress-delivery mechanism may be contributing to the
      shortened pregnancy length in depressed women.

PMID- 21093927
TI  - The association between menstrual cycle and traumatic memories.
AB  - BACKGROUND: Women in the mid-luteal phase of the menstrual cycle have been shown
      to have stronger emotional memories than other women. We investigated the extent
      to which experiencing a traumatic event during the luteal phase of the menstrual
      cycle is associated with stronger traumatic flashback memories. METHODS:
      Consecutive female patients admitted to hospital after traumatic injury (n=138)
      were assessed for days since last menstruation, as well as assessment of
      flashbacks. Twenty three (17%) women were in the mid-luteal phase (18-24) days at
      the time of trauma exposure and 29 (21%) were in the mid-luteal phase at the time
      of assessment. RESULTS: Women were more likely to experience flashback memories
      if they were in the luteal phase during the trauma (22% vs. 9%), adjusted OR:
      3.64 [95%CI: 0.99-13.29] after controlling for injury severity, age, trauma type,
      and mild traumatic brain injury. Women in the luteal phase at assessment were
      4.89 times more likely to have flashbacks. Adjusted OR: 4.89 [95%CI: 1.39-17.86].
      CONCLUSIONS: Increased glucocorticoid release associated with the luteal phase of
      the menstrual cycle may facilitate consolidation of trauma memories.

PMID- 21093928
TI  - Contributions of the glucocorticoid receptor polymorphism (Bcl1) and childhood
      abuse to risk of bulimia nervosa.
AB  - This study evaluated the hypothesis that traumatic stress can increase risk of
      bulimia nervosa (BN) in individuals who are genetically disposed towards lower
      modulation of physiological stress reactions. We explored the extent to which
      childhood abuse (physical or sexual), variants of a main glucocorticoid receptor
      (GR) polymorphism (Bcl1), or their interaction, differentiated women with and
      without BN. Women seeking treatment for BN (N=129) and non-eating-disordered
      comparison women (N=98) provided blood samples for assays of the Bcl1
      polymorphism, and completed structured interviews assessing eating symptoms,
      psychiatric symptoms and childhood abuse. Compared to normal-eaters, bulimic
      women were significantly more likely to carry the low-function Bcl1 C allele (CC
      or CG genotypes), to report a history of childhood abuse and, more importantly,
      to be positive for both factors. We interpret our findings as indicating that
      traumatic stress, when impacting individuals disposed to lower GR modulation, can
      be etiological for BN.

PMID- 21093929
TI  - Gene associations - SNPs and function.

PMID- 21093931
TI  - Clinical and biological heterogeneity of autoimmune myasthenia gravis.
AB  - Although myasthenia gravis (MG) has long been considered a well-established
      autoimmune disease associated with autoantibodies, which are convincingly
      pathogenic, accumulating data indicate both clinical and biological heterogeneity
      similar to many other putative autoimmune disorders. In a subset of patients,
      thymus plays a definite role: thymic autoimmunity results in generation of
      autoantibodies within the thymus, which cross-react with antigens at the
      neuromuscular junction, or thymoma leads to deficient central tolerance and
      impaired T cell selection. Heterogeneity on the autoantibody level may be
      associated with genetic heterogeneity and clinical phenotypes with different
      treatment responses.

PMID- 21093930
TI  - 2D immunomic approach for the study of IgG autoantibodies in the experimental
      model of multiple sclerosis.
AB  - 2D-immunomics may be useful in the identification of autoantigens in neurological
      autoimmune diseases, but its application may be limited by denaturation of target
      proteins. Here we compared the capacity of a single or multiple antigens to
      elicit autoantibodies targeting multiple neural autoantigens by ELISA and 2D
      immunomics. We induced experimental autoimmune encephalomyelitis (EAE) with MBP
      peptide(89-104), total MBP or spinal cord homogenate. Both techniques showed anti
      MBP IgG only after immunization with total MBP. In addition, 2D-immunomics
      revealed the presence in EAE mice of autoantibodies targeting other neural
      proteins, some displaying partial sequence homology with MBP. The present finding
      by 2D-immunomics of multiple neural proteins targeted by autoantibodies generated
      by a single antigen may help to explain the complex autoimmune response observed
      in multiple sclerosis.

PMID- 21093932
TI  - Onconeural antibodies: improved detection and clinical correlations.
AB  - Onconeural antibodies are found in many patients with paraneoplastic neurological
      syndromes (PNS) and define the disease as paraneoplastic. The study describes the
      presence of onconeural antibodies and PNS in 555 patients with neurological
      symptoms and confirmed cancer within five years, and compares the diagnostic
      accuracy of different antibody assays (immunoprecipitation, immunofluorescence
      and immunoblot). Onconeural antibodies were found in 11.9% of the patients by
      immunoprecipitation, in 7.0% by immunofluorescence and in 6.3% by immunoblot. PNS
      were present in 81.8% of the cancer patients that were seropositive by
      immunoprecipitation. Immunofluorescence and immunoblot failed to detect
      onconeural antibodies in almost one third of the PNS cases.

PMID- 21093933
TI  - TGF-beta signaling is altered in the peripheral blood of subjects with multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a central nervous system inflammatory disorder with
      evidence of peripheral immune dysregulation. Abnormalities of the immune
      suppressive cytokine TGF-beta have been reported, but not fully defined, in MS.
      Through a pathway-focused expression profiling of the peripheral blood, we found
      abnormalities of TGF-betaRII, SMAD4 and SMAD7 expression in subjects with MS, and
      reduction in the levels of TGF-beta regulated genes, indicating an overall
      reduction in TGF-beta signaling in MS. The response to exogenous TGF-beta was
      intact, however, indicating an extrinsic defect of TGF-beta signaling in MS.
      These results indicate that TGF-beta control is diminished in MS.

PMID- 21093934
TI  - Induction of frond abscission by metals and other toxic compounds in Lemna minor.
AB  - Fronds of the duckweed Lemna minor L. clone St form colonies of different sizes
      on the basis of stipes connecting mother and daughter fronds for some time after
      the development of daughter fronds. All the metals (AsO(4)(3-), AsO(2)(-),
      Cd(2+), CrO(4)(2-), Co(2+), Cu(2+), Ni(2+), Hg(2+), Tl(+) and Zn(2+)) and one non
      metal (SeO(4)(2-), SeO(3)(2-)) tested here induced frond abscission, thus
      decreasing the colony size on the basis of a novel mechanism of abscission
      described recently. Concentration-response curves were created based on
      percentages of frond abscission after 7 and 24h of toxic compound application,
      and response concentrations were calculated accordingly. The following
      conclusions could be drawn: (1) in most cases the response demonstrates less
      sensitivity than the bio test based on the ISO protocol 20079. (2) Even applying
      1mM of the metals, AsO(4)(3-), CrO(4)(2-), Co(2+) and Zn(2+) did not reach the
      half-maximal effects. (3) The concentration-response curves are bell-shaped with
      AsO(2-), Cd(2+), Hg(2+), SeO(3)(2-) and Tl(+), which demonstrates that abscission
      is induced by lower but not by higher concentrations. (4) Frond abscission shows
      fast and sensitive effects (24h) for Ag(+), Cu(2+), AsO(2-), SeO(4)(2-), SeO(3)(2
      ) and Tl(+). The mechanisms and responses described here quantitatively for the
      first time complement and explain observations within the frame of the ISO
      protocol. Therefore, frond abscission should be regularly reported in the
      standard test protocols as abscission always indicates massive physiological
      effects.

PMID- 21093935
TI  - A new automated system to identify a consistent sampling position to make tissue
      Doppler and transmitral Doppler measurements of E, E' and E/E'.
AB  - BACKGROUND: Transmitral pulse wave (PW) Doppler and annular tissue Doppler
      velocity measurements provide valuable diagnostic and prognostic information.
      However, they depend on an echocardiographer manually selecting positions to make
      the measurements. This is time-consuming and open to variability, especially by
      less experienced operators. We present a new, automated method to select
      consistent Doppler velocity sites to measure blood flow and muscle function.
      METHODS: Our automated algorithm combines speckle tracking and colour flow
      mapping to locate the septal and lateral mitral valve annuli (to measure peak
      early diastolic velocity, E') and the mitral valve inflow (to measure peak inflow
      velocity, E). We also automate peak velocity measurements from resulting PW
      Doppler traces. The algorithm-selected locations and time taken to identify them
      were compared against a panel of echo specialists - the current "gold standard".
      RESULTS: The algorithm identified positions to measure Doppler velocities within
      3.6 +/- 2.2mm (mitral inflow), 3.2 +/- 1.8mm (septal annulus) and 3.8 +/- 1.5mm
      (lateral annulus) of the consensus of 3 specialists. This was less than the
      average 4mm fidelity with which the specialists could themselves identify the
      points. The automated algorithm could potentially reduce the time taken to make
      these measurements by 60 +/- 15%. CONCLUSIONS: Our automated algorithm identified
      sampling positions for measurement of mitral flow, septal and lateral tissue
      velocities as reliably as specialists. It provides a rapid, easy method for new
      specialists and potentially non-specialists to make automated measurements of key
      cardiac physiological indices. This could help support decision-making, without
      introducing delay and extend availability of echocardiography to more patients.

PMID- 21093936
TI  - Effect of smoking cessation on the number and adhesive properties of early
      outgrowth endothelial progenitor cells.
AB  - BACKGROUND: Endothelial progenitor cells participate in angiogenesis and vascular
      repair, and cardiovascular risk factors may reduce their numbers or impair their
      functional properties. Cigarette smoking is a leading cause of preventable
      cardiovascular death, however, the functional properties of these cells before
      and after discontinuation of tobacco use have not been systematically analyzed.
      METHODS: We examined changes in the number and function of early outgrowth
      endothelial progenitor cells (EPC), isolated from individuals (n=144; mean age,
      47.8 +/- 12.0 years; 43% males; more than 50% with additional cardiovascular risk
      factors or disease) who successfully completed a 5-week smoking cessation (SC)
      programme. RESULTS: SC significantly reduced total white blood cell count (WBC;
      P<0.0001), plasma LDL cholesterol (P=0.0002) and fibrinogen (P<0.0001) levels,
      but did not alter the number of circulating CD34(+), VEGFR2(+) or CD34(+),
      CD133(+) cells (P=0.14 and 0.57, respectively). Fewer acLDL(+), lectin(+) cells
      could be expanded from peripheral blood mononuclear cells in comparison to
      baseline (P<0.001). Furthermore, SC was associated with reduced EPC adhesion to
      fibronectin (P<0.001) or TNFalpha-activated endothelial cells (P=0.003), and a
      diminished incorporation of EPC into endothelial cell networks (P=0.035).
      Mechanistically, significantly reduced beta1- and beta2-integrin expression
      (P<0.001 and 0.007) and lower contents of intracellular reactive oxygen species
      (P<0.007) were detected in EPC following SC, in addition to reduced plasma
      asymmetric dimethyl-L-arginine (ADMA) levels (P=0.0003). CONCLUSIONS: Our
      findings suggest that the oxidative and inflammatory stress reduction associated
      with smoking cessation impair the adhesiveness of monocyte-derived EPC.

PMID- 21093937
TI  - MR-pro-atrial natriuretic peptide (MR-proANP) predicts short- and long-term
      outcomes in respiratory tract infections: a prospective validation study.
AB  - BACKGROUND: Previous research found precursor levels of the atrial natriuretic
      peptide (MR-proANP) to be promising prognostic markers. This study aims to
      validate these findings and describe patterns of MR-proANP in a large cohort of
      patients with lower respiratory tract infections. METHODS: We conducted a
      multicenter prospective cohort study, and measured MR-proANP in patients with
      lower respiratory tract infections on admission, and days 3, 5 and 7. The
      prognostic value of MR-proANP for predicting 30-day and 180-day mortalities was
      evaluated. We stratified MR-proANP levels a priori into quartiles, and compared
      it with severity of illness using the pneumonia severity index. RESULTS: A total
      of 1359 patients, including 925 with community-acquired pneumonia, were enrolled.
      The mortality risk at days 30 and 180 significantly increased with increasing MR
      proANP quartiles (<84 pmol/L, 84-158 pmol/L, >158-311 pmol/L, and >311 pmol/L).
      This was true for low-risk, as well as high-risk subjects (pneumonia severity
      index classes I-III and IV-V). In Kaplan-Meier survival curves, MR-proANP
      quartiles significantly separated survivors from non-survivors in the overall
      cohort (p log-rank<0.001), and in low-risk (p log-rank<0.03) and high-risk (p log
      rank=0.007) pneumonia severity index patients at day 30. In multivariate logistic
      regression analysis, MR-proANP was an independent risk factor for 30-day and 180
      day mortalities (odds ratio per unit increase of log transformation MR-proANP
      level: 5.58, 95%CI 1.97-15.82 and 5.08, 95%CI 2.44-10.60). CONCLUSION: This study
      confirms the high prognostic performance of MR-proANP for short- and long-term
      mortality, particularly its high negative predictive value, in lower respiratory
      tract infections and community-acquired pneumonia, thereby complementing clinical
      risk assessment with the pneumonia severity index.

PMID- 21093938
TI  - Lethal myocardial reperfusion injury: a necessary evil?
AB  - Despite being the most effective means of limiting infarct size, coronary
      reperfusion comes at a price and induces additional damage to the myocardium.
      Lethal reperfusion injury (death of myocytes that were viable at the time of
      reperfusion) is an increasingly acknowledged phenomenon. There are many
      interconnected mechanisms involved in this type of cell death. Calcium overload
      (generating myocyte hypercontracture), rapid recovery of physiological pH,
      neutrophil infiltration of the ischemic area, opening of the mitochondrial
      permeability-transition-pore (PTP), and apoptotic cell death are among the more
      important mechanisms involved in reperfusion injury. The activation of a group of
      proteins called reperfusion injury salvage kinases (RISK) pathway confers
      protection against reperfusion injury, mainly by inhibiting the opening of the
      mitochondrial PTP. Many interventions have been tested in human trials triggered
      by encouraging animal studies. In the present review we will explain in detail
      the main mechanism involved in reperfusion injury, as well as the various
      approaches (pre-clinical and human trials) performed targeting these mechanisms.
      Currently, no intervention has been consistently shown to reduce reperfusion
      injury in large randomized multicenter trials, but the research in this field is
      intense and the future is highly promising.

PMID- 21093939
TI  - HbA1c and atrial fibrillation: a cross-sectional study in Japan.
AB  - BACKGROUND: The aim of the present study was to investigate whether the
      prevalence of atrial fibrillation (AF) is associated with the level of glycated
      hemoglobin (HbA1c) in Japanese adults in Kurashiki-city. METHODS: Adult residents
      (? 40 years old) were examined twice, in 2006 and 2007. Electrocardiography was
      conducted to determine the presence of AF. After categorizing all participants
      into two groups (HbA1c <6.5% as low group and ? 6.5% as high group), factors
      independently associated with the prevalence of AF were investigated in total
      cohort, low and high groups using multivariate logistic regression analysis.
      RESULTS: Of the total 52,448 participants (median age, 72 years; range, 65-78
      years; 17,980 men), AF prevalence was 2.2% (1161/52,448). After classifying all
      participants by HbA1c level, the proportion of participants with AF was 2.2%
      (1073/49,498) in the low group and 3.0% (88/2950) in high group (p=0.005). AF was
      significantly associated with cardiac disease (OR, 5.78; 95%CI, 5.07-6.58;
      p<0.001), elevating HbA1c (OR, 1.57; 95%CI, 1.33-1.84; p<0.001), increasing age
      (OR, 1.40; 95%CI, 1.30-1.51; p<0.001), and male sex (OR, 1.27; 95%CI, 1.10-1.47;
      p=0.001) in low group and was related to cardiac disease (OR, 4.85; 95%CI, 3.08
      7.62; p<0.001) and age (OR, 1.45; 95%CI, 1.09-1.93; p=0.010) in high group. After
      adjusted age, gender, vascular risk factors, cardiac disease, and eGFR, elevating
      HbA1c (OR, 1.18; 95%CI, 1.09-1.28; p<0.001) was the factor in association with
      AF. CONCLUSIONS: The presence of AF appears to be associated with the level of
      HbA1c, especially in patients with HbA1c <6.5%.

PMID- 21093940
TI  - Long-term prognosis after hospital admission for acute myocardial infarction from
      1987 to 2006.
AB  - BACKGROUND: Recent population-based estimates for long-term cardiovascular
      disease (CVD) mortality after hospitalization for a first acute myocardial
      infarction (AMI) are not well established. METHODS: Data from the Swedish
      hospital discharge and death registries were used to record all first-ever
      hospital admissions in patients (n=348,772) 35-84 years with AMI from 1987 to
      2006 and subsequent all-cause and CVD case fatality during up to 5 years.
      RESULTS: During the 20-year period, 28-day case fatality was reduced by almost
      two thirds in patients aged <75 years. For cases with a first AMI 1999-2002 long
      term case fatality for men surviving the first 28 days and <55 years was
      10.3/1000 person years, with rates of 23.6, 58.0 and 137.0 for men aged 55-64, 65
      74 and 75-84 years. Corresponding figures for women were 10.5, 24.3, 51.8, 124.1
      deaths/1000 years. In 1999-2002 estimated long-term risk of fatal CVD (based on
      survival until 2007) for men below 55 years was 6.1/1000 years, and 13.8, 34.6,
      92.9 for men aged 55-64, 65-74, and 75-84 years, respectively. Corresponding
      figures for women were 4.8, 11.9, 30.1, 86.2/1000 years. The total reduction in
      CVD case fatality was two thirds among patients aged <55 and approximately one
      third among those aged 75-84. CONCLUSIONS: Long-term case fatality after
      hospitalization for AMI decreased markedly from 1987 to 2006, particularly with
      respect to CVD mortality and in younger patients. However, because of a steep
      increase in case fatality with age and a large proportion of older patients, long
      term prognosis overall still remains poor.

PMID- 21093941
TI  - Risk stratification in patients with chronic heart failure based on metabolic
      immunological, functional and haemodynamic parameters.
AB  - BACKGROUND: A vast array of parameters has been proposed to predict mortality in
      chronic heart failure (CHF). Their applicability into clinical practice remains
      challenging due to economical and availability considerations. METHODS AND
      RESULTS: We studied serum uric acid, total cholesterol, and soluble tumour
      necrosis factor receptor 1 (sTNF-R1) in 114 CHF patients (63.0 +/- 1.0 years,
      NYHA functional class I/II/III/IV: 11/34/54/15) recruited prospectively into a
      metabolic study program. All patients underwent assessment of left ventricular
      ejection fraction and measurement of peak oxygen consumption (pVO(2)). Patients
      were followed for 24 months or until death. A total of 31 patients died;
      cumulative survival was 78% (95% confidence interval [CI] 70-86%) and 73% (65
      81%) at 12 and 24 months, respectively. In single predictor Cox proportional
      hazard analysis, uric acid, pVO2, sTNFR-1, LVEF (all p<0.0001) and cholesterol
      (p<0.02) all predicted survival. All parameters remained significant predictors
      of death after multivariable adjustment (all p<0.02). Receiver-operator
      characteristic (ROC) curve analyses showed that uric acid and sTNF-R1 are equally
      strong with regards to their prognostic performance in CHF like pVO(2,) but even
      better than LVEF. The combination of pVO(2), LVEF, uric acid, and sTNF-R1 in ROC
      statistics turned out as the best model with the highest prognostic value in CHF
      (AUC: 0.91, sensitivity: 90.4, specificity: 74.2, p=0.0001). CONCLUSION:
      Including metabolic-immunological parameters into risk assessment might result in
      a better risk stratification than modeling based on clinical parameters alone,
      probably due to a better reflection of CHF as multisystem disease. We suggest
      metabolic-immunological parameters to be tested in larger populations.

PMID- 21093942
TI  - Randomized study on provisional stenting with sirolimus-eluting stent vs. bare
      metal stent for the treatment of true coronary bifurcations: the PROSUMER
      (PROvisional with sirolimus-eluting vs. bare metal stents in truE bifuRcations)
      study.

PMID- 21093943
TI  - Intra-aortic balloon pump in intensive cardiac care: a registry in Florence.

PMID- 21093944
TI  - Cardiac tamponade caused by acupuncture: a review of the literature.
AB  - This systematic review aims to summarize all reported cases of cardiac tamponade
      after acupuncture. Five electronic databases and our own files were searched for
      reports of cardiac tamponade after acupuncture. No restrictions in time or
      language were imposed. Data were extracted by two independent reviewers according
      to predefined criteria. We found a total of 26 cases. In 14 patients, the
      complications were fatal. In most instances, there is little doubt about
      causality. We conclude that cardiac tamponade is a serious, often fatal
      complication after acupuncture. As it is theoretically avoidable, acupuncturists
      should be trained to minimize the risk.

PMID- 21093945
TI  - Vieussens' ring with congenitally hypoplastic left coronary arterial system.

PMID- 21093946
TI  - Simulation of the seasonal cycles of bird, equine and human West Nile virus
      cases.
AB  - The West Nile virus (WNV) is an arthropod-borne virus (arbovirus) circulating in
      a natural transmission cycle between mosquitoes (enzootic vectors) and birds
      (amplifying hosts). Additionally, mainly horses and humans (dead-end hosts) may
      be infected by blood-feeding mosquitoes (bridge vectors). We developed an
      epidemic model for the simulation of the WNV dynamics of birds, horses and humans
      in the U.S., which we apply to the Minneapolis metropolitan area (Minnesota). The
      SEIR-type model comprises a total of 19 compartments, that are 4 compartments for
      mosquitoes and 5 compartments or health states for each of the 3 host species. It
      is the first WNV model that simulates the seasonal cycle by explicitly
      considering the environmental temperature. The latter determines model parameters
      responsible for the population dynamics of the mosquitoes and the extrinsic
      incubation period. Once initialized, our WNV model runs for the entire period
      2002-2009, exclusively forced by environmental temperature. Simulated incidences
      are mainly determined by host and vector population dynamics, virus transmission
      and herd immunity, respectively. We adjusted our WNV model to fit monthly totals
      of reported bird, equine and human cases in the Minneapolis metropolitan area.
      From this process we estimated that the proportion of actually WNV-induced dead
      birds reported by the Centers for Disease Control and Prevention is about 0.8%,
      whereas 7.3% of equine and 10.7% of human cases were reported. This is consistent
      with referenced expert opinions whereby about 10% of equine and human cases are
      symptomatic (the other 90% of asymptomatic cases are usually not reported).
      Despite the restricted completeness of surveillance data and field observations,
      all major peaks in the observed time series were caught by the simulations.
      Correlation coefficients between observed and simulated time series were R=0.75
      for dead birds, R=0.96 for symptomatic equine cases and R=0.86 for human
      neuroinvasive cases, respectively.

PMID- 21093947
TI  - Effect of osmotic stress and culture density on invasiveness of Listeria
      monocytogenes strains.
AB  - The effect of osmotic stress on its capacity to invade the human enterocytic cell
      line HT-29 was studied in the early log through the stationary phase in 10 L.
      monocytogenes strains representing three genetically independent lineages. The
      results demonstrate that the transition of the bacteria from the log to the
      stationary phase results in a stepwise reduction of invasiveness. This effect was
      heterogeneous in the studied L. monocytogenes population, as the range of
      invasiveness reduction between the log and stationary phases varied from 10- to
      380-fold depending on the strain. Ten-minute exposure to 0.3 M NaCl was
      sufficient to generate invasiveness alteration. No significant change in
      invasiveness induction caused by osmotic stress was found between the different
      points of the log phase (OD600 0.4-1.2), being significantly different in the
      early log phase (OD600 0.2-0.3) and in the stationary phase after 18 h of
      culture. The level of internalins and opuCA transcripts in response to osmotic
      stress did not correlate with invasiveness alteration in most L. monocytogenes
      strains. Prolongation of stress exposure to 1 h and an increase in NaCl
      concentration from 0.3 to 1.8 M had no significant effect on a further increase
      in invasiveness. Short exposure times and low NaCl concentrations were sufficient
      for the generation of maximal invasiveness response of L. monocytogenes. It
      appears that although stationary-phase bacteria exhibit lower invasiveness than
      log-phase bacteria, they have a greater capacity to enhance their pathogenicity
      in response to stress.

PMID- 21093949
TI  - Recognizing autoimmune hepatitis: scores help, but no more.

PMID- 21093948
TI  - Glyoxylate is a substrate of the sulfate-oxalate exchanger, sat-1, and increases
      its expression in HepG2 cells.
AB  - BACKGROUND & AIMS: Hyperoxaluria is a major problem causing nephrolithiasis.
      Little is known about the regulation of oxalate transport from the liver, the
      main organ for oxalate synthesis, into the circulation. Since the sulfate anion
      transporter-1(sat-1) is present in the sinusoidal membrane of hepatocytes and
      translocates oxalate, its impact on increased oxalate synthesis was studied.
      METHODS: Sat-1 expressing oocytes were used for cis-inhibition, trans
      stimulation, and efflux experiments with labelled sulfate and oxalate to
      demonstrate the interactions of oxalate, glyoxylate, and glycolate with sat-1.
      HepG2 cells were incubated with oxalate and its precursors (glycine,
      hydroxyproline, glyoxylate, and glycolate). Changes in endogenous sat-1 mRNA
      expression were examined using real-time PCR. After incubation of HepG2 cells in
      glyoxylate, sat-1 protein-expression was analysed by Western blotting, and
      sulfate uptake into HepG2 cells was measured. RT-PCR was used to screen for mRNA
      of other transporters. RESULTS: While oxalate and glyoxylate inhibited sulfate
      uptake, glycolate did not. Sulfate and oxalate uptake were trans-stimulated by
      glyoxylate but not by glycolate. Glyoxylate enhanced sulfate efflux. Glyoxylate
      was the only oxalate precursor stimulating sat-1 mRNA-expression. After
      incubation of HepG2 cells in glyoxylate, both sat-1 protein-expression and
      sulfate uptake into the cells increased. mRNA-expression of other transporters in
      HepG2 cells was not affected by glyoxylate treatment. CONCLUSIONS: The oxalate
      precursor glyoxylate was identified as a substrate of sat-1. Upregulated
      expression of sat-1 mRNA and of a functional sat-1 protein indicates that
      glyoxylate may be responsible for the elevated oxalate release from hepatocytes
      observed in hyperoxaluria.

PMID- 21093950
TI  - Pathogenesis of lipid metabolism disorder in hepatitis C: polyunsaturated fatty
      acids counteract lipid alterations induced by the core protein.
AB  - BACKGROUND & AIMS: Disturbance in lipid metabolism is one of the features of
      chronic hepatitis C, being a crucial determinant of the progression of liver
      fibrosis. Experimental studies have revealed that the core protein of hepatitis C
      virus (HCV) induces steatosis. METHODS: The activities of fatty acid metabolizing
      enzymes were determined by analyzing the fatty acid compositions in HepG2 cells
      with or without core protein expression. RESULTS: There was a marked accumulation
      of triglycerides in core-expressing HepG2 cells. While the oleic/stearic acid
      (18:1/18:0) and palmitoleic/palmitic acid ratio (16:1/16:0) were comparable in
      both the core-expressing and the control cells, there was a marked accumulation
      of downstream product, 5,8,11-eicosatrienoic acid (20:3(n-9)) in the core
      expressing HepG2 cells. The addition of eicosatetraynoic acid, which inhibits
      delta-6 desaturase activity which is inherently high in HepG2 cells, led to a
      marked accumulation of oleic and palmitoleic acids in the core-expressing cells,
      showing that delta-9 desaturase was activated by the core protein.
      Eicosapentaenoic acid (20:5(n-3)) or arachidonic acid (20:4(n-6)) administration
      significantly decreased delta-9 desaturase activity, the concentration of 20:3(n
      9), and triglyceride accumulation. This lipid metabolism disorder was associated
      with NADH accumulation due to mitochondrial dysfunction, and was reversed by the
      addition of pyruvate through NADH utilization. CONCLUSIONS: The fatty acid
      enzyme, delta-9 desaturase, was activated by HCV core protein and polyunsaturated
      fatty acids counteracted this impact of the core protein on lipid metabolism.
      These results may open up new insights into the mechanism of lipid metabolism
      disorder associated with HCV infection and provide clues for the development of
      new therapeutic devices.

PMID- 21093951
TI  - The GAPs between hepatocellular carcinoma and RAS.

PMID- 21093952
TI  - Influenza vaccine for healthy adult workers: an issue for health authorities or
      employers?
AB  - OBJECTIVE: To contribute to the debate whether extending public coverage of
      influenza vaccination to healthy workers is cost-effective, particularly in the
      perspective of EU countries. METHODS: First, we reviewed the recent international
      literature on the extension of vaccination to subjects aged 50-64 years in highly
      developed countries. Second, we estimated the broad economic impact of influenza
      vaccination on the Italian healthy adult working population. Finally, we ran a
      pilot observational study to assess the healthcare and labour outcomes of
      influenza vaccination on the employees of our organization. RESULTS: The
      methodological weaknesses of the studies reviewed, all built on models, undermine
      the credibility of their optimistic results. The more cautious the model design,
      the less favourable the final results, as our conservative analysis on the
      Italian setting confirmed. The only common result was a steady relationship
      between potential vaccination benefits and indirect costs of absenteeism from
      work. This "modelling-based evidence" was confirmed by our internal survey:
      vaccinated workers showed less tendency to stay at home during influenza-like
      illness episodes and their relapses. CONCLUSIONS: The economic advantage of
      extending public influenza vaccination to healthy adult workers is still
      uncertain and mainly relates to the indirect costs of productivity losses, making
      the extension strategy more a labour than a health issue.

PMID- 21093953
TI  - Setting health care capitations through diagnosis-based risk adjustment: a
      suitable model for the English NHS?
AB  - The English system of health resource allocation has been described as the
      apotheosis of the area-level approach to setting health care capitations.
      However, recent policy developments have changed the scale at which commissioning
      decisions are made (and budgets allocated) with important implications for
      resource allocation. Doubts concerning the legitimacy of applying area-based
      formulae used to distribute resources between Primary Care Trusts (PCTs) to the
      much smaller scale required by Practice Based Commissioning (PBC) led the English
      Department of Health (DH) to introduce a new approach to setting health care
      budgets. To this end, practice-level allocations for acute services are now
      calculated using a diagnosis-based capitation model of the kind used in the
      United States and several other systems of competitive social health insurance.
      The new Coalition Government has proposed that these budgets are directly
      allocated to GP 'consortia', the new commissioning bodies in the NHS. This paper
      questions whether this is an appropriate development for a health system in which
      the major objective of resource allocation is to promote equal opportunity of
      access for equal needs. The chief reservation raised is that of circularity and
      the perpetuation of resource bias, the concern being that an existing social,
      demographic and geographical bias in the use of health care resources will be
      reinforced through the use of historic utilisation data. Demonstrating that there
      are legitimate reasons to suspect that this will be the case, the paper poses the
      question whether health systems internationally should more openly address the
      key limitations of empirical methods that select risk adjusters on the basis of
      existing patterns of health service utilisation.

PMID- 21093955
TI  - Experiments with genitalia: a commentary.
AB  - There has been a recent burst of studies of the function of genitalia, many of
      which share several important shortcomings. Given that further studies on this
      topic are likely (there are probably millions of species showing rapid genital
      divergence), I discuss the studies critically to promote clear formulation of
      hypotheses and interpretation of results in the future. I also emphasize some
      possibly important but neglected variables, including female stimulation,
      phylogenetic contexts, and the behavior of male genitalia, and outline simple
      techniques that could improve future studies.

PMID- 21093954
TI  - Polymorphisms of MLH1 and MSH2 genes and the risk of lung cancer among never
      smokers.
AB  - Mismatch repair (MMR) plays an important role in repairing nucleotide mismatches
      during DNA replication. Defects in MMR genes are associated with some sporadic
      tumors. MLH1 and MSH2 are two of the MMR genes. We conducted a case-control study
      to investigate the associations between the risk of lung cancer and genetic
      polymorphisms in the MLH1 and MSH2 genes. The SNP genotypes were determined in
      730 lung cancer patients and 730 healthy controls that were frequency matched for
      the age, gender, and smoking status. Among the SNP polymorphisms, -93A>G
      (rs1800734), which is located in the promoter region of MLH1, was significantly
      associated with the risk of lung cancer. The GG genotype for MLH1 -93A>G was
      associated with a significantly increased risk of lung cancer compared with the
      AA genotype among the never-smoking group (adjusted OR=1.64, 95% CI=1.10-2.44;
      P=0.013). Consistently, the haplotype of MLH1 with one -93G risk allele was
      associated with the risk of lung cancer compared with the AA haplotype among the
      never-smoking group. Furthermore, the risk of MLH1 -93A>G polymorphism in the
      never-smoking group related to lung adenocarcinoma was modulated by environmental
      tobacco smoke (ETS) exposure status, with a significant gene-ETS interaction
      (P=0.042). No evidence was found of the association between MSH2 and the lung
      cancer risk. In conclusion, our data suggest that the MLH1 -93A>G polymorphism
      may contribute to the etiology of lung cancer, particularly in never smokers.
      This study also suggests that MLH1 -93A>G polymorphisms and ETS exposure have a
      role in the tumorigenesis of lung adenocarcinoma among never smokers.

PMID- 21093956
TI  - Naloxone and alum synergistically augment adjuvant activities of each other in a
      mouse vaccine model of Salmonella typhimurium infection.
AB  - Alum is the most commonly used adjuvant for human vaccination but is a poor
      inducer of cell mediated immunity and T helper 1 (Th1) responses. We have
      previously shown that naloxone (NLX), which is a general opioid antagonist, acts
      as an effective adjuvant in enhancing vaccine-induced cellular immunity and Th1
      immune responses. Here, we tested the efficacy of an alum-NLX mixture, as a new
      adjuvant, in the induction of humoral and cellular immunity in response to
      endotoxin-removed lysate (ERL) of Salmonella typhimurium (S. typhimurium) as a
      model vaccine. BALB/c mice were divided into five vaccination groups. Mice in the
      experimental groups received either the ERL vaccine alone or in combination with
      the adjuvant alum, NLX or the alum-NLX mixture. Mice in the negative control
      group received phosphate-buffered saline. All mice were immunized on days 0 and
      7. Two weeks after the last immunization, immune responses to S. typhimurium were
      assessed. Our results indicate that including the alum-NLX mixture as an adjuvant
      during vaccination increased the ability of the ERL vaccine to enhance lymphocyte
      proliferation, shifted the immune response toward a Th1 profile and increased S.
      typhimurium-specific IgG, IgG2a and the ratio of IgG2a to IgG1. This resulted in
      improved protective immunity against S. typhimurium. In conclusion, administering
      an alum-NLX mixture adjuvant in combination with the ERL vaccine enhances both
      humoral and cellular immunity, and shifts the immune response to a Th1 pattern.

PMID- 21093957
TI  - Nodularin uptake and induction of oxidative stress in spinach (Spinachia
      oleracea).
AB  - The bloom-forming cyanobacterium Nodularia spumigena produces toxic compounds,
      including nodularin, which is known to have adverse effects on various organisms.
      We monitored the primary effects of nodularin exposure on physiological
      parameters in Spinachia oleracea. We present the first evidence for the uptake of
      nodularin by a terrestrial plant, and show that the exposure of spinach to
      cyanobacterial crude water extract from nodularin-producing strain AV1 results in
      inhibition of growth and bleaching of the leaves. Despite drastic effects on
      phenotype and survival, nodularin did not disturb the photosynthetic performance
      of plants or the structure of the photosynthetic machinery in the chloroplast
      thylakoid membrane. Nevertheless, the nodularin-exposed plants suffered from
      oxidative stress, as evidenced by a high level of oxidative modifications
      targeted to various proteins, altered levels of enzymes involved in scavenging of
      reactive oxygen species (ROS), and increased levels of alpha-tocopherol, which is
      an important antioxidant. Moreover, the high level of cytochrome oxidase (COX
      II), a typical marker for mitochondrial respiratory protein complexes, suggests
      that the respiratory capacity is increased in the leaves of nodularin-exposed
      plants. Actively respiring plant mitochondria, in turn, may produce ROS at high
      rates. Although the accumulation of ROS and induction of the ROS scavenging
      network enable the survival of the plant upon toxin exposure, the upregulation of
      the enzymatic defense system is likely to increase energetic costs, reducing
      growth and the ultimate fitness of the plants.

PMID- 21093958
TI  - [Management of posteriorly dislocated lens material after complicated
      phacoemulsification. The vitreoretinal surgeon's point of view].
AB  - Posterior dislocation of lens material is a serious complication of
      phacoemulsification. Its prognosis depends on timely treatment, well-planned by
      cataract and vitreoretinal surgeons working in collaboration. Pars plana
      vitrectomy with removal of the dislocated material is nearly always mandatory on
      a short-term basis in order to prevent and/or treat any further complication,
      mainly uveitis, hypertony, corneal edema, cystoid macular edema, and retinal
      detachment. The best time to implant and perform pars plana vitrectomy is still a
      matter of controversy. The best predictor of final visual acuity is the visual
      acuity before vitrectomy.

PMID- 21093959
TI  - [Nitric oxide, biomarker of experimental autoimmune uveitis induced by S
      antigen].
AB  - INTRODUCTION: uveitis is an intraocular inflammation and one of the most severe
      and frequent manifestations of Behcet disease. S antigen (S Ag) is a highly
      conserved retinal protein implicated in the mechanism of the physiopathology in
      Behcet disease. This autoantigen is used in different animal models for
      experimental autoimmune uveitis (EAU) development, particularly in Behcet
      uveitis. Nitric oxide (NO) production has been reported in this disease by
      several groups and mainly by our team. MATERIALS AND METHODS: in this study, we
      investigated the development of Behcet uveitis in an experimental model using the
      Wistar rat after treatment with S antigen. This antigen was isolated and purified
      from bovine retina by gel filtration chromatography using Sephadex G-200. The
      rats were immunized with 10MUg of S Ag. We evaluated the changes in nitric oxide
      metabolite production in plasma using the Griess reaction, during the 7th, 14th,
      and 21st days post-immunization. Furthermore, deleterious effects by S antigen on
      retinal tissue were assessed in a histological study. RESULTS: the results showed
      a significant increase in NO production in Wistar rats treated with S Ag in
      comparison with controls. We noted with interest that the clinical stages of EAU
      correlated with NO production. Furthermore, S Ag had several deleterious effects
      on Wistar rat retina. CONCLUSION: this study indicated in vivo elevation of NO
      levels, which was observed before retinal tissue damage. Nitric oxide appears to
      be a good marker for a poor prognosis in this experimental model. Moreover,
      oxidative stress can be considered the primary step in pathogenesis inducing the
      destruction of retinal photoreceptors. Collectively, our data could be helpful in
      the development of strategies for diagnosing patients with Behcet uveitis.

PMID- 21093960
TI  - High-resolution hyperspectral imaging of the retina with a modified fundus
      camera.
AB  - PURPOSE: to examine the practical feasibility of developing a hyperspectral
      camera from a Zeiss fundus camera and to illustrate its use in imaging diabetic
      retinopathy and glaucoma patients. METHODS: the original light source of the
      camera was replaced with an external lamp filtered by a fast tunable liquid
      crystal filter. The filtered light was then brought into the camera through an
      optical fiber. The original film camera was replaced by a digital camera. Images
      were obtained in normals and patients (primary open angle glaucoma, diabetic
      retinopathy) recruited at the Manchester Royal Eye Hospital. RESULTS: a series of
      eight images were captured across 495- to 720-nm wavelengths, and recording time
      was less than 1.6s. The light level at the cornea was below the ANSI limits, and
      patients judged the measurement to be very comfortable. Images were of high
      quality and were used to generate a pixel-to-pixel oxygenation map of the optic
      nerve head. Frame alignment is necessary for frame-to-frame comparison but can be
      achieved through simple methods. CONCLUSIONS: we have developed a hyperspectral
      camera with high spatial and spectral resolution across the whole visible
      spectrum that can be adapted from a standard fundus camera. The hyperspectral
      technique allows wavelength-specific visualization of retinal lesions that may be
      subvisible using a white light source camera. This hyperspectral technique may
      facilitate localization of retinal and disc pathology and consequently facilitate
      the diagnosis and management of retinal disease.

PMID- 21093962
TI  - Split hypoglossal-facial nerve neurorrhaphy for treatment of the paralyzed face.
AB  - BACKGROUND: Several methods of neural rehabilitation for facial paralysis using
      12-7 transfers have been described. The purpose of this study is to report on a
      series for dynamic reinnervation of the paralyzed face by using a split 12-7
      nerve transposition. The goals of this procedure are to minimize tongue morbidity
      and to provide good facial reinnervation. METHODS: Prospective case series.
      Melolabial crease discursion, overall facial movement, and degree of tongue
      atrophy and mobility were recorded. RESULTS: Thirteen patients underwent facial
      reanimation using a split hypoglossal-facial nerve transfer with postoperative
      follow-up to 58 months (range, 6-58 months). All patients achieved excellent rest
      symmetry and facial tone. Of 13 patients, 10 had measurable coordinated movement
      and discursion of their melolabial crease. Of 13 patients, 12 had mild to
      moderate ipsilateral tongue atrophy. The mean time to onset of visible
      reinnervation was 3 months. CONCLUSION: Split hypoglossal-facial nerve
      transposition provides good rehabilitation of facial nerve paralysis with reduced
      lingual morbidity. Long-term rest symmetry and potential learned movement can be
      achieved. This technique may provide a favorable alternative to the traditional
      method of complete hypoglossal sacrifice or jump grafting.

PMID- 21093961
TI  - [Study and prevention of contact lens-related microbial keratitis with a
      standardized questionnaire].
AB  - INTRODUCTION: microbial keratitis is a significant health concern for the one
      million wearers of contact lenses and their ophthalmologists, with some
      potentially modifiable risk factors. The number of risk factors for contact lens
      related microbial keratitis has been described, but many of them still remain
      assumed or unknown. PATIENTS AND METHODS: a multicenter prospective case-control
      study was conducted in 12 French university hospitals (Besancon, Bordeaux, Dijon,
      Fort-de-France, Grenoble, Limoges, Lyon, Nancy, Nantes, Paris, Marseille and
      Strasbourg) beginning in July 2007 on contact lens wearers presenting with
      microbial keratitis and on healthy contact lens wearers. Patients and healthy
      wearers were interviewed using a 51-item anonymous standardized questionnaire to
      determine subject demographics and contact lens wear history. RESULTS: two
      hundred and fifty-six patients with microbial keratitis were included. One
      hundred and thirteen healthy contact lenses wearers were surveyed. Cosmetic
      contact lens wear highly increased the relative risk (RR) of microbial keratitis
      (RR, 16.5). Time since the last visit to an ophthalmologist longer than 1 year
      (RR, 3.4) or prescription by someone other than an ophthalmologist (RR, 7.6) also
      increased the risk of microbial keratitis. Education on lens care and handling
      was deficient (hand washing: RR, 2.2; rub and rinse: RR, 2.7). DISCUSSION: a
      standardized questionnaire is a powerful tool to determine risk factors for
      contact lens-related microbial keratitis, but also to analyze individual mistakes
      in contact lenses use and care.

PMID- 21093963
TI  - Is there any association between esophagogastric endoscopic findings and
      laryngeal cancer?
AB  - PURPOSE: The aim of the study was to survey the association between prevalence of
      acid-related inflammation in the upper digestive tract and laryngeal cancer.
      MATERIALS AND METHODS: A case-control study was done in an otolaryngology ward at
      an academic university. Totally, 65 patients with laryngeal cancer and 65 cancer
      free matched controls underwent esophagogastroduodenoscopy, and endoscopic
      findings were collected. RESULTS: In the case group, positive endoscopic findings
      were significantly higher than the control group (87.7% vs 58.5%; P < .001).
      Laryngeal cancer patients had erosive esophagitis, and gastritis +/- other
      findings more than the control group (48 vs 29 cases) and the difference was
      statistically significant. CONCLUSION: The difference between endoscopic findings
      in cases and controls was statistically significant. Severe inflammation and
      erosion existed in patients with laryngeal cancer that could be due to increased
      acid secretion. Our study supported the hypothesis that gastric acid and pepsin
      play a role in laryngeal cancer.

PMID- 21093965
TI  - Synthesis and crystal structure of two new dinuclear cobalt(II) complexes
      interaction with HeLa cells.
AB  - Two novel dinuclear complexes [Co(2)(L)(2)(phen)(2).2H(2)O](n) (1),
      [Co(2)(L)(2)(bipy)(2)](n) (2) (where phen=1,10-phenanthroline, bipy=2,2'
      bipyridine, and L=biphenyl-2,4'-dicarboxylic acid) have been synthesized and
      characterized using IR, (1)H NMR, element analysis and single-crystal X-ray
      diffractometry. The binding of the complexes with HC-DNA (HeLa cells DNA, which
      was extracted by ourselves) was investigated by fluorescence spectrum. The
      experimental results show that the two complexes have the ability to bind with
      extracted HC-DNA. Gel electrophoresis assay demonstrates the ability of the
      complexes to cleave the extracted HC-DNA. The complexes exhibit a higher
      cytotoxicity against tumor cells as against normal cells in vitro. Further more,
      the apoptotic tests indicate that the complexes have an apoptotic effect on HeLa
      cells.

PMID- 21093967
TI  - [Update on infective endocarditis].
AB  - Infective endocarditis has continuously evolved since its first clinical
      description by William Osler in the late 19th century. The epidemiological and
      microbiological profile of the disease has changed as the result of the progress
      of the medical care and demographic mutation in industrialized countries.
      Furthermore, advances in anti-infective therapy and in cardiovascular surgery
      have contributed to an improvement in the management and the prognosis of this
      severe infectious disease. During the past decade, the recommendations on
      antibiotic prophylaxis against infective endocarditis have changed dramatically.
      Guidelines on management of infective endocarditis and state-of-the-art articles
      have been published recently and this work aims to outline current
      recommendations about this evolving disease.

PMID- 21093966
TI  - Isoxazolidinyl polycyclic aromatic hydrocarbons as DNA-intercalating antitumor
      agents.
AB  - The second generation and an isosteric series of isoxazolidinyl polycyclic
      aromatic hydrocarbons, as DNA-intercalator agents designed to act on remotely
      implanted tumors, have been synthesized in good yields according to the 1,3
      dipolar cycloaddition methodology. The structure of the obtained cycloadducts has
      been determined by NOE experiments and supported by computational studies at PM3
      level. The utility of this new template in the synthesis of structures designed
      to capitalize on its intercalative properties has been examined. All the obtained
      compounds have been tested for their in vitro cytotoxic activity and the most
      potent of them showed an IC(50) of 9 MUM upon the human lung cancer (A-549) cell
      and a binding constant, for the intercalation with calf thymus DNA, of 9.6 *
      10(4) M(-1). Biological and docking studies showed that these compounds complex
      exclusively by intercalation between base pairs, approaching the DNA from its
      minor groove, with a neat selectivity for the AT or GC nucleobases.

PMID- 21093968
TI  - A rapidly equilibrating, thin film, passive water sampler for organic
      contaminants; characterization and field testing.
AB  - Improving methods for assessing the spatial and temporal resolution of organic
      compound concentrations in marine environments is important to the sustainable
      management of our coastal systems. Here we evaluate the use of ethylene vinyl
      acetate (EVA) as a candidate polymer for thin-film passive sampling in waters of
      marine environments. Log K(EVA-W) partition coefficients correlate well (r(2) =
      0.87) with Log K(OW) values for selected pesticides and polychlorinated biphenyls
      (PCBs) where Log K(EVA-W) = 1.04 Log K(OW) + 0.22. EVA is a suitable polymer for
      passive sampling due to both its high affinity for organic compounds and its ease
      of coating at sub-micron film thicknesses on various substrates. Twelve-day field
      deployments were effective in detecting target compounds with good precision
      making EVA a potential multi-media fugacity meter.

PMID- 21093964
TI  - The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation
      on numbers of central catecholaminergic neurons.
AB  - Parkinson's disease (PD), an age-related movement disorder, is characterized by
      severe catecholaminergic neuron loss in the substantia nigra pars compacta
      (SN(PC))-ventral tegmental area (VTA) and locus coeruleus (LC). To assess the
      stability of these central catecholaminergic neurons following an acute episode
      of severe inflammation, 6 to 22 month old C57/Bl6 mice received a maximally
      tolerated dose of lipopolysaccharide (LPS) followed by euthanasia 2 hours later
      to assay peak levels of peripheral and central cytokines; and, 14 weeks later for
      computerized stereology of tyrosine hydroxylase-immunopositive (tyrosine
      hydroxylase-positive [TH+]) neurons in the SN(PC)-VTA and LC. Two hours after
      LPS, cytokine levels varied in an age-related manner, with the greatest
      peripheral and central elevations in old and young mice, respectively. Severe
      inflammation failed to cause loss of TH+ neurons in SN(PC)-VTA or LC; however,
      there was an age-related decline in these TH+ neurons in LPS-treated and control
      groups. Thus, unknown mechanisms in the B6 mouse brain appear to protect against
      catecholaminergic neuron loss following an acute episode of severe inflammation,
      while catecholaminergic neuron loss occurs during normal aging.

PMID- 21093969
TI  - National survey of the levels of persistent organochlorine pesticides in the
      breast milk of mothers in China.
AB  - The occurrence of persistent organochlorine pesticides (OCPs) in breast milk
      samples collected from mothers from twelve provinces in mainland China was
      investigated. Dichlorodiphenyltrichloroethanes (DDTs) were the most prevalent
      agent, followed by HCHs and HCB, whereas levels of chlordane compounds, drins and
      mirex were lower. The relatively lower DDE/DDT ratio in the Fujian rural area
      suggested more recent exposure to DDT than in other areas. The mean level of DDTs
      in breast milk from the southern China was higher than those from northern China
      (p < 0.05). A positive correlation was observed between concentration of DDTs in
      human milk and consumption of animal-origin food, suggesting that this parameter
      could play an important part in influencing OCPs burdens in lactating women. The
      mean estimated daily intakes of different OCPs for breastfed infants were lower
      than the tolerable daily intake.

PMID- 21093970
TI  - Mental time travel into the past and the future in healthy aged adults: an fMRI
      study.
AB  - Remembering the past and envisioning the future rely on episodic memory which
      enables mental time travel. Studies in young adults indicate that past and future
      thinking share common cognitive and neural underpinnings. No imaging data is yet
      available in healthy aged subjects. Using fMRI, we scanned older subjects while
      they remembered personal events (PP: last 12 months) or envisioned future plans
      (FP: next 12 months). Behaviorally, both time-periods were comparable in terms of
      visual search strategy, emotion, frequency of rehearsal and recency of the last
      evocation. However, PP were more episodic, engaged a higher state of autonoetic
      consciousness and mental visual images were clearer and more numerous than FP.
      Neuroimaging results revealed a common network of activation (posterior cingulate
      cortex, precuneus, prefrontal cortex, hippocampus) reflecting the use of similar
      cognitive processes. Furthermore, the episodic nature of PP depended on
      hippocampal and visuo-spatial activations (occipital and angular gyri), while,
      for FP, it depended on the inferior frontal and lateral temporal gyri, involved
      in semantic memory retrieval. The common neural network and behavior suggests
      that healthy aged subjects thought about their future prospects in the past. The
      contribution of retrospective thinking into the future that engages the same
      network as the one recruited when remembering the past is discussed. Within this
      network, differential recruitment of specific areas highlights the episodic
      distinction between past and future mental time travel.

PMID- 21093971
TI  - [Weight variation after reduction mammary surgery: retrospective study of 100
      cases].
AB  - INTRODUCTION: Patients desiring breast reduction are often in overweight, and
      describe interferences with their daily life and minor psychological problems. We
      undertook this study to establish the pre- and postoperative weight pattern by
      age and histological breast type. PATIENTS AND METHODS: A retrospective review
      was performed on 100 consecutive patients who underwent bilateral reduction
      mammaplasty for macromastia (>300g per breast) in 2007. The patients were
      categorized by age in two groups: group 1 (G1) comprising the 50 younger patients
      (mean age: 35.5 years) and group 2 (G2) comprising the 50 older (mean age: 47.2
      years). We obtained data points including: preoperative and postoperative weight
      pattern according to age and histological subtypes, calculation of body mass
      index (BMI), data from surgery including amount of resection, postoperative
      course and complications. RESULTS: Patients consulting for breast reduction are
      moderately overweight (mean BMI: 28.22 confounded all ages). Preoperative weight
      loss is low despite systematic surgeon request (<0.5 % on average waiting time of
      6.45 months). The postoperative weight loss is higher in young patients with
      glandular form of HTM (respectively -4.76 kg for glandulofibrous type and -3kg
      for fibrous, which corresponds to a loss of 6.5 and 4.1 % of their body weight).
      The impact of surgery on the patient's psychological condition is better in young
      patients. CONCLUSION: This study demonstrated that postoperative weight loss
      after breast reduction are significant only in young patients with a
      constitutional type of macromastia (glandular or mixed forms). We believe that in
      addition to the functional improvement associated with surgery, these young
      patients lose weight they initially take to harmonize their silhouette.

PMID- 21093972
TI  - Shivering during therapeutic hypothermia after cardiac arrest.

PMID- 21093974
TI  - Time-dependent effectiveness of chest compression-only and conventional
      cardiopulmonary resuscitation for out-of-hospital cardiac arrest of cardiac
      origin.
AB  - BACKGROUND: Little is known about the effect of the type of bystander-initiated
      cardiopulmonary resuscitation (CPR) for prolonged out-of-hospital cardiac arrest
      (OHCA). OBJECTIVES: To evaluate the time-dependent effectiveness of chest
      compression-only and conventional CPR with rescue breathing for witnessed adult
      OHCA of cardiac origin. METHODS: A nationwide, prospective, population-based,
      observational study of the whole population of Japan included consecutive OHCA
      patients with emergency responder resuscitation attempts from 1 January 2005 to
      31 December 2007. Multiple logistic regression analysis was performed to assess
      the contribution of the bystander-initiated CPR technique to favourable
      neurological outcomes. RESULTS: Among 55014 bystander-witnessed OHCA of cardiac
      origin, 12165 (22.1%) received chest compression-only CPR and 10851 (19.7%)
      received conventional CPR. For short-duration OHCA (0-15min after collapse),
      compression-only CPR had a higher rate of survival with favourable neurological
      outcome than no CPR (6.4% vs. 3.8%; adjusted odds ratio (OR), 1.55; 95%
      confidence interval (CI), 1.38-1.74), and conventional CPR showed similar
      effectiveness (7.1% vs. 3.8%; adjusted OR, 1.78; 95% CI, 1.58-2.01). For the long
      duration arrests (>15min), conventional CPR showed a significantly higher rate of
      survival with favourable neurological outcome than both no CPR (2.0% vs. 0.7%;
      adjusted OR, 1.93; 95% CI, 1.27-2.93) and compression-only CPR (2.0% vs. 1.3%;
      adjusted OR, 1.56; 95% CI, 1.02-2.44). CONCLUSIONS: For prolonged OHCA of cardiac
      origin, conventional CPR with rescue breathing provided incremental benefit
      compared with either no CPR or compression-only CPR, but the absolute survival
      was low regardless of type of CPR.

PMID- 21093975
TI  - Effectiveness of highly purified human menopausal gonadotropin in intra-uterine
      insemination.
AB  - OBJECTIVE: In assisted reproductive techniques it is important to find a balance
      between high pregnancy and acceptable multiple pregnancy rates. In IVF treatment,
      stimulation with highly purified human menopausal gonadotropin (hMG) results in
      comparable or even higher pregnancy rates at lower oocyte yields compared to
      recombinant FSH. Since highly purified hMG contains LH activity, a number of the
      advantages of highly purified hMG may be attributed to this LH activity. In IUI
      treatment the effectiveness of highly purified hMG has been barely investigated.
      The aim of this study was to examine the effectiveness of highly purified hMG in
      IUI patients treated with a mild stimulation protocol. STUDY DESIGN: In this
      retrospective study 378 patients were included, receiving 1400 IUI cycles between
      January 2006 and December 2007. Patients were first treated with three subsequent
      natural cycles without controlled ovarian hyperstimulation, followed by three
      subsequent cycles stimulated with highly purified hMG. Primary outcomes were
      ongoing pregnancy rate and multifollicular growth. Secondary outcomes were
      multiple pregnancy and miscarriage rates. Primary and secondary outcomes were
      expressed in percentages with associated 95% confidence intervals (95%CI).
      Differences in the outcomes between natural and stimulated cycles were calculated
      using chi(2) tests. Statistical differences were determined at P < 0.05. RESULTS:
      Ongoing pregnancy rates increased from 6% (95%CI 4.7-7.7) per natural cycle to
      7.4% (95%CI 5.2-10.3) per highly purified hMG stimulated cycle (p = 0.34). The
      highest ongoing pregnancy rate was observed in the fifth treatment cycle (10.8%
      (95%CI 6.6-17)), which is significantly higher than the ongoing pregnancy rate in
      the unstimulated group (p = 0.03). In the highly purified hMG group three (9.7%
      (95%CI 3.3-24.9)) of the ongoing pregnancies were twin pregnancies, in the
      unstimulated group there was one (1.7% (95%CI 0.3-9.0)) twin pregnancy (p =
      0.08). CONCLUSION: Our results indicate that mild stimulation with highly
      purified hMG in IUI treatment results in an acceptable balance between ongoing
      and multiple pregnancy rates. Future prospective trials should compare mild
      stimulation protocols to protocols directly starting with controlled ovarian
      hyperstimulation. Furthermore, these trials should compare other types and
      dosages of gonadotropins.

PMID- 21093976
TI  - The impact of in vitro fertilization on health of the children: an update.
AB  - Infertile couples make up approximately 10% of the worldwide population, and
      around 1% of current live births are a result of assisted reproductive technology
      (ART). Since the time that this technology was first applied, many studies have
      been performed in order to determine the risk associated with infertility
      treatments. Short- and long-term risks have been identified, which confirm that
      the major complications are due to multiple pregnancies. In a previous study we
      described in detail the main reproductive processes, the techniques for in vitro
      fertilization (IVF) and the risks associated with each of them, with a focus on
      intracytoplasmic sperm injection (ICSI). In this review we provide an update from
      2007 to the present. In particular, in addition to new information on post
      pregnancy complications and infant morbidity and malformations, we report data on
      rare syndromes, including recent case reports. Although data are controversial,
      an association between IVF and a minor increase in the incidence of birth defects
      has been confirmed. Several lines of evidence also suggest that there may be a
      link between ART and psychological disorders in the parents and the child.
      Finally, recent findings draw attention to the need for accurate clinical and
      psychological counselling of couples before any treatment decisions are made.

PMID- 21093977
TI  - Spatial variations of human health risk associated with exposure to chlorination
      by-products occurring in drinking water.
AB  - During disinfection, chlorine reacts with organic matter present in drinking
      water and forms various undesirable chlorinated by-products (CBPs). This paper
      describes a study of the spatial variability of human health risk (i.e., cancer
      effects) from CBP exposure through drinking water in a specific region. The
      region under study involves nine drinking water distribution systems divided into
      several zones based on their characteristics. The spatial distribution of cancer
      risk (CR) was estimated using two years of data (2006-2008) on various CBP
      species. In this analysis, trihalomethanes (THMs) and haloacetic acids (HAAs)
      served as surrogates for CBPs. Three possible routes of exposure (i.e., via
      ingestion, inhalation and dermal contact) were considered for each selected
      compound. The cancer risk assessment involved estimating a unit risk (R(T)) in
      each zone of the selected distribution systems. A probabilistic analysis based on
      Monte Carlo simulations was employed. Risk assessment results showed that cancer
      risk varied between systems, but also within individual systems. As a result, the
      population of the same region was not exposed to the same risk associated with
      CBPs in drinking water. Unacceptable levels (i.e., R(T) > 10(-4)) for the
      estimated CR were determined for several zones in the studied region. This study
      demonstrates that a spatial-based analysis performed to represent the spatial
      distribution of risk estimates can be helpful in identifying suitable risk
      management strategies. Suggestions for improving the risk analysis procedure are
      also presented.

PMID- 21093978
TI  - Parry-Romberg syndrome with chronic focal encephalitis: two cases.

PMID- 21093979
TI  - Inhibition of poly (ADP-ribose) polymerase-1 enhances doxorubicin activity
      against liver cancer cells.
AB  - The purpose of this study was to investigate whether PARP-1 inhibition sensitizes
      human liver cancer cell lines to doxorubicin treatment. Both the addition of PARP
      1 inhibitor (ANI) and depletion by means of stable siRNA significantly enhanced
      the growth inhibition induced by the DNA damage agents used. This effect was
      associated with an accumulation of unrepaired DNA, with a reduction in EGFR and
      Bcl-xL gene expression as well as with positive annexin-V staining. These results
      provide novel evidence of the direct role of PARP-1 in tumour chemoresistance in
      relation to its effects on the transcription of key genes involved in tumour
      survival.

PMID- 21093980
TI  - Melanoma-associated antigen genes - an update.
AB  - To date, dozens of melanoma-associated antigens (MAGE) have been identified.
      Based on the differences in tissue-specific gene expression and gene structure,
      the MAGE family has been divided into two big subfamilies: MAGE-I and MAGE-II.
      MAGE-I genes were identified as a group of highly attractive targets for cancer
      immunotherapy because of their wide expression in a variety of malignant tumors
      but silent in normal adult cells except germ-line cells lacking human leukocyte
      antigen (HLA) expression. However, little is known regarding the functions of
      MAGE family members in cell activities. In this review, we briefly described the
      classification of MAGE family members and their expression pattern in cancer. We
      also summarized the mechanism of MAGE activation and the functions of MAGE family
      members in cell cycle progression and apoptosis. We also discussed what is known
      of immunotherapy targeting MAGE family.

PMID- 21093981
TI  - Influence of persulfate ions on the removal of phenol in aqueous solution using
      electron beam irradiation.
AB  - The removal of phenol (Co = 100 MUM) during electron beam irradiation was studied
      in pure water and in the presence of HCO(3)(-) and Br(-) ions. It was found that
      the introduction of S(2)O(8)(2-) ions (1mM), by generating SO(4)(-) radicals
      increases the radiation yield of phenol removal. 90% removal of phenol was
      obtained with radiation doses 600 and 1200 Gy with and without S(2)O(8)(2-) ions
      respectively. This system induced smaller oxygen consumption with smaller
      concentration of catechol and hydroquinone found in the solution. HCO(3)(-) and
      Br(-) have an inhibiting effect in the presence as in the absence of S(2)O(8)(2
      ). In most cases, the introduction of S(2)O(8)(2-) ions in water radiolysis
      system can advantageously increase the yield of organic compounds removal by
      oxidation.

PMID- 21093982
TI  - Oxidation of triclosan by ferrate: reaction kinetics, products identification and
      toxicity evaluation.
AB  - The oxidation of triclosan by commercial grade aqueous ferrate (Fe(VI)) was
      investigated and the reaction kinetics as a function of pH (7.0-10.0) were
      experimentally determined. Intermediate products of the oxidation process were
      characterized using both GC-MS and RRLC-MS/MS techniques. Changes in toxicity
      during the oxidation process of triclosan using Fe(VI) were investigated using
      Pseudokirchneriella subcapitata growth inhibition tests. The results show that
      triclosan reacted rapidly with Fe(VI), with the apparent second-order rate
      constant, k(app), being 754.7 M(-1) s(-1) at pH 7. At a stoichiometric ratio of
      10:1 (Fe(VI):triclosan), complete removal of triclosan was achieved. Species
      specific rate constants, k, were determined for reaction of Fe(VI) with both the
      protonated and deprotonated triclosan species. The value of k determined for
      neutral triclosan was 6.7(+/-1.9)*10(2) M(-1) s(-1), while that measured for
      anionic triclosan was 7.6(+/-0.6)*10(3) M(-1) s(-1). The proposed mechanism for
      the oxidation of triclosan by the Fe(VI) involves the scission of ether bond and
      phenoxy radical addition reaction. Coupling reaction may also occur during Fe(VI)
      degradation of triclosan. Overall, the degradation processes of triclosan
      resulted in a significant decrease in algal toxicity. The toxicity tests showed
      that Fe(VI) itself dosed in the reaction did not inhibit green algae growth.

PMID- 21093983
TI  - Photooxidation processes for an azo dye in aqueous media: modeling of degradation
      kinetic and ecological parameters evaluation.
AB  - Three photooxidation processes, UV/H(2)O(2), UV/S(2)O(8)(2-) and UV/O(3) were
      applied to the treatment of model wastewater containing non-biodegradable organic
      pollutant, azo dye Acid Orange 7 (AO7). Dye degradation was monitored using
      UV/VIS and total organic carbon (TOC) analysis, determining decolorization, the
      degradation/formation of naphthalene and benzene structured AO7 by-products, and
      the mineralization of model wastewater. The water quality during the treatment
      was evaluated on the bases of ecological parameters: chemical (COD) and
      biochemical (BOD(5)) oxygen demand and toxicity on Vibrio fischeri determining
      the EC(50) value. The main goals of the study were to develop an appropriate
      mathematic model (MM) predicting the behavior of the systems under investigation,
      and to evaluate the toxicity and biodegradability of the model wastewater during
      treatments. MM developed showed a high accuracy in predicting the degradation of
      AO7 when considering the following observed parameters: decolorization,
      formation/degradation of by-products and mineralization. Good agreement of the
      data predicted and the empirically obtained was confirmed by calculated standard
      deviations. The biodegradability of model wastewater was significantly improved
      by three processes after mineralizing a half of the initially present organic
      content. The toxicity AO7 model wastewater was decreased as well. The differences
      in monitored ecological parameters during the treatment indicated the formation
      of different by-products of dye degradation regarding the oxidant type applied.

PMID- 21093984
TI  - Mechanism study of nitrate reduction by nano zero valent iron.
AB  - This study investigates the fate of nitrogen species during nitrate reduction by
      nano-scale zero valent iron (NZVI) and related reaction mechanisms. The NZVI used
      for the experiments was prepared by chemical reduction without a stabilizing
      agent. NZVI has great ability to reduce nitrate. However, the question of what
      end-product results from nitrate reduction by NZVI has sparked controversy.
      Establishing nitrogen mass balance by quantitative analysis of aqueous phase and
      gas-phase nitrogen species, this study clearly determines that nitrate was
      converted to ammonium ion followed by ammonia stripping under a strong alkaline
      condition, which leads to a decrease in the total aqueous nitrogen amount.
      Moreover, some of the major reactions, which consisted of nitrate reduction,
      ammonia production, and ammonia stripping were modelled by pseudo first-order
      kinetics. According to the model estimation results, additional reaction
      mechanisms would exist in an early stage of reaction. This might be due to the
      adsorption and desorption reaction which could be explained by the core-shell
      structure model.

PMID- 21093985
TI  - Slurry analysis of cadmium and copper collected on 11-mercaptoundecanoic acid
      modified TiO2 core-Au shell nanoparticles by flame atomic absorption
      spectrometry.
AB  - Separation/preconcentration of copper and cadmium using TiO(2) core-Au shell
      nanoparticles modified with 11-mercaptoundecanoic acid and their slurry analysis
      by flame atomic absorption spectrometry were described. For this purpose, at
      first, titanium dioxide nanoparticles were coated with gold shell by reducing the
      chloroauric acid with sodium borohydride and then modified with 11
      mercaptoundecanoic acid. The characterization of modified nanoparticles was
      performed using ultra-violet spectroscopy and dynamic light scattering. Copper
      and cadmium were then collected on the prepared sorbent by batch method. The
      solid phase loaded with the analytes was separated by centrifugation and the
      supernatant was removed. Finally, the precipitate was slurried and directly
      aspirated into the flame for the determination of analytes. Thus, elution step
      and its all drawbacks were eliminated. The effects of pH, amount of sorbent,
      slurry volume, sample volume and diverse ions on the recovery were investigated.
      After optimization of experimental parameters, the analytes in different
      certified reference materials and spiked water samples were quantitatively
      recovered with 5% RSD. The analytes were enriched up to 20-fold. Limits of
      detection (N=10, 3sigma) for copper and cadmium were 0.28 and 0.15 ng mL(-1),
      respectively.

PMID- 21093986
TI  - Compressive auto-indexing in femtosecond nanocrystallography.
AB  - Ultrafast nanocrystallography has the potential to revolutionize biology by
      enabling structural elucidation of proteins for which it is possible to grow
      crystals with 10 or fewer unit cells on the side. The success of
      nanocrystallography depends on robust orientation-determination procedures that
      allow us to average diffraction data from multiple nanocrystals to produce a
      three-dimensional (3D) diffraction data volume with a high signal-to-noise ratio.
      Such a 3D diffraction volume can then be phased using standard crystallographic
      techniques. "Indexing" algorithms used in crystallography enable orientation
      determination of diffraction data from a single crystal when a relatively large
      number of reflections are recorded. Here we show that it is possible to obtain
      the exact lattice geometry from a smaller number of measurements than standard
      approaches using a basis pursuit solver.

PMID- 21093987
TI  - Modelling population dynamics and response to management options in the poultry
      red mite Dermanyssus gallinae (Acari: Dermanyssidae).
AB  - The poultry red mite Dermanyssus gallinae is a major pest and widespread
      ectoparasite of laying hens and other domestic and wild birds. Under optimal
      conditions, D. gallinae can complete its lifecycle in less than 10 days, leading
      to rapid proliferation of populations in poultry systems. This paper focuses on
      developing a theoretical model framework to describe the population dynamics of
      D. gallinae. This model is then used to test the efficacy and residual effect of
      different control options for managing D. gallinae. As well as allowing
      comparison between treatment options, the model also allows comparison of
      treatment efficacies to different D. gallinae life stages. Three different means
      for controlling D. gallinae populations were subjected to the model using
      computer simulations: mechanical cleaning (killing once at a given time all
      accessible population stages), sanitary clearance (starving the mite population
      for a given duration, e.g. between flocks) and acaricide treatment (killing a
      proportion of nymphs and adults during the persistence of the treatment).
      Simulations showed that mechanical cleaning and sanitary clearance alone could
      not eradicate the model D. gallinae population, although these methods did delay
      population establishment. In contrast, the complete eradication of the model D.
      gallinae population was achieved by several successive acaricide treatments in
      close succession, even when a relatively low treatment level was used.

PMID- 21093988
TI  - Cortisol response to acute trauma and risk of posttraumatic stress disorder.
AB  - This study sought to characterize the variability of the acute cortisol response
      following trauma and its relationship to posttraumatic stress disorder (PTSD).
      Forty eight participants were recruited within 24h of a traumatic accident
      requiring hospital admission. A saliva sample was collected at 08.00 h and 16.00
      h 2 days, 1 month and 6 months after hospital admission, together with 24-h urine
      collection. Participants completed a dexamethasone suppression test (0.5mg DEX at
      21.00 h) at each follow up, together with self-report questionnaires. The
      Clinician Administered PTSD Scale (CAPS) was administered at 1 and 6 months to
      identify PTSD. Prevalence of PTSD was 27% at 1 month and 21% at 6 months. PTSD
      symptoms at 6 months were negatively correlated with salivary cortisol at 08.00 h
      on day 2 (r=-0.36, p=0.04), but positively correlated with 16.00 h cortisols
      (r=0.41, p=0.03). A lower rise in cortisol at 08.00 h on day 2 was associated
      with an increase in risk of PTSD at both 1 month (OR=1.411 (1.017, 1.957)) and 6
      months (OR=1.411 (1.066, 1.866)). At 1 month, 70% of participants with PTSD
      suppressed cortisol to more than 90% of pre-dex levels compared with 25% without
      PTSD (chi(2)=6.77, p=0.034). Urinary cortisol excretion was not different between
      groups at any time point. The findings support a hypothesis that sensitization of
      the HPA axis and enhanced suppression of cortisol following the dexamethasone
      suppression test are established early in the disease process.

PMID- 21093989
TI  - Does the prostate retain an endogenous antiviral defense system suggesting a past
      viral etiology for cancer?
AB  - Evidence of viral infection of the prostate is presented, and consists of viral
      isolation as well as antigen and genomic detection of integrated or episomal
      forms. Prior infection from "ancient" exogenous retroviruses is suggested by
      residual endogenous forms. The presence of an antiviral defense system based upon
      interferon induction has been suggested for the testes. I suggest that a similar
      system is also present in the prostate. Prostate cell lines (or tissue) can be
      tested directly for expression of interferon-gamma (IFN-gamma). However, enhanced
      expression should be induced by IFN inducers such as bispecific oligonucleotides
      having double stranded regions or poly I:C. RNA can be extracted and RT-PCR
      performed using commercially available primers for gamma interferon. Evidence for
      the presence of an interferon based anti-viral system would be indicated not only
      by interferon expression, but also its enhanced expression following exposure to
      the inducers. Gamma interferon is primarily associated with lymphocytic
      expression and immune regulation. Demonstration of its controlled expression in
      non-immune cells would support the hypotheses suggested here.

PMID- 21093990
TI  - Nutrient contribution of total and lean beef in diets of US children and
      adolescents: National Health and Nutrition Examination Survey 1999-2004.
AB  - This study examined the nutritional contribution of total beef and lean beef (LB)
      to the diet of US children and adolescents using the US Department of Agriculture
      definition of LB as defined in MyPyramid. Twenty-four hour dietary recall data
      from children 4-8 years of age [y] (n=2474), 9-13 y (n=3273), and adolescents 14
      18 y (n=4044) participating in the NHANES 1999-2004 were assessed. LB was defined
      as beef with <=9.28 grams [g] fat/100 g (excess was discretionary fat). Means and
      standard errors were determined using appropriate sample weights. Consumption of
      LB contributed significantly to intake of protein and many key nutrients such as
      vitamins B6 and B12, zinc, iron, niacin, phosphorus, and potassium by US children
      and adolescents without providing significantly to intakes of total fat,
      saturated fatty acids, or sodium.

PMID- 21093991
TI  - A C/T mutation in microRNA target sites in BMP5 gene is potentially associated
      with fatness in pigs.
AB  - Bone morphogenetic protein 5 (BMP5) gene was suggested to be a potential
      positional candidate gene for fatness trait QTLs on SSC7. Here by comparative
      sequencing of BMP5 gene in Meishan (MS) and Large White (LW) pigs, one SNP
      *131C>T in 3' un-translated region was detected. Association analysis results in
      322 LW*MS F(2) pigs showed that CC pigs had thinner back fatness and heavier ham
      than TC (P<0.05 or P<0.1), and had a higher fat percentage and a lower lean meat
      percentage (P<0.1) than TT. Moreover, this C/T transition was predicted to alter
      BMP5 interaction with let-7c and miR-184 by using RNA22 and RNAhybrid. The
      negative expression of BMP5 gene with let-7c and miR-184 detected from miRNAs
      overexpression in swine fibroblast, indicating these 2 miRNAs might participate
      in the translational inhibition of BMP5 gene. Overall, SNP *131C>T might be a
      good marker for fatness traits.

PMID- 21093992
TI  - Risks associated with crack cocaine smoking among exotic dancers in Baltimore,
      MD.
AB  - BACKGROUND: There is a dearth of research focusing on sex work in exotic dance
      clubs. We conducted a cross-sectional study to examine the prevalence and
      correlates of crack cocaine smoking among a sample of exotic dancers. METHODS:
      The "block," a historical red-light district in downtown Baltimore, MD, is
      comprised of 30 adult-entertainment establishments. Between 01/09 and 08/09, we
      conducted a survey with exotic dancers (N=98). The survey explored demographic,
      and drug and sexual/drug risk behaviors. Bivariate and multivariate analysis was
      conducted using Poisson regression with robust variance estimates to examine
      correlates of current crack smoking. RESULTS: Crack cocaine smokers compared to
      non-crack cocaine smokers were significantly more likely to report: older age (29
      vs. 23 years, respectively, p<0.0001); being White (79% vs. 50%, respectively,
      p=0.008); having been arrested (93% vs. 67%, respectively, p=0.008); daily
      alcohol consumption (36% vs. 17%, p=0.047); current heroin injection (57% vs.
      13%, p<0.001); and current sex exchange (79% vs. 30%, p<0.001). In the presence
      of other variables, crack cocaine smokers compared to non-crack cocaine smokers
      were significantly older, more likely to report current heroin injection, and
      more likely to report current sex exchange. DISCUSSION: We found high levels of
      drug use and sexual risk behaviors as well as a number of risks behaviors
      associated with crack cocaine smoking among this very under-studied population.
      Targeted interventions are greatly needed.

PMID- 21093993
TI  - Equine herpesvirus-1 infected peripheral blood mononuclear cell subpopulations
      during viremia.
AB  - Infection with equine herpesvirus-1 (EHV-1) causes respiratory disease, late term
      abortions and equine herpesvirus myeloencephalitis (EHM) and remains an important
      problem in horses worldwide. Despite increasing outbreaks of EHM in recent years,
      our understanding of EHM pathogenesis is still limited except for the knowledge
      that a cell-associated viremia in peripheral blood mononuclear cells (PBMCs) is a
      critical link between primary respiratory EHV-1 infection and secondary
      complications such as late-term abortion or EHM. To address this question our
      objective was to identify which PBMC subpopulation(s) are infected during viremia
      and may therefore play a role in transmitting the virus to the vascular
      endothelium of the spinal cord or pregnant uterus. PBMCs from 3 groups of animals
      were collected between days 4 and 9 following experimental infection with EHV-1
      strain Findlay/OH03 or strain Ab4. PBMCs were labeled with primary antibodies
      selective for CD4+ or CD8+ T lymphocytes, B-lymphocytes, or monocytes and
      positively selected using magnetic bead separation. Cell numbers and EHV-1 genome
      numbers in each subpopulation were then determined using quantitative PCR for
      beta-actin and the EHV-1 glycoprotein B, respectively. Viral genomic DNA was
      found in all PBMC subpopulations; the CD8+ lymphocytes were most frequently
      positive for viral DNA, followed by B-lymphocytes. These differences were
      statistically significant in horses infected with the EHV-1 strain Findlay/OH03,
      and ponies with Ab4. These results differ from what has been reported in in vitro
      studies, and indicate that different PBMC subpopulations may play different roles
      in EHV-1 viremia.

PMID- 21093994
TI  - Comparative study of liver vitellogenin gene expression and oocyte yolk
      accumulation in wild and captive Atlantic bluefin tuna (Thunnus thynnus L.).
AB  - The sequence of vitellogenin A (VgA) and vitellogenin B (VgB) cDNAs in Atlantic
      bluefin tuna (Thunnus thynnus L.) were determined, and vitellogenin expression
      levels in the liver and oocyte yolk accumulation were compared in wild and
      captive-reared individuals. Liver and ovary samples were taken from 31
      individuals reared experimentally in three commercial Atlantic bluefin tuna
      fattening sites in the Mediterranean Sea and from 33 wild individuals caught by
      commercial traps during the fish's migration towards their Mediterranean spawning
      grounds. The total length of VgA cDNA was 5585 nucleotides and that of VgB was
      5267 nucleotides. The identity and similarity between deduced amino acid
      sequences of VgA and VgB were 60% and 78%, respectively. The Atlantic bluefin
      tuna VgA and VgB amino acid sequences have high similarities with those of other
      teleost fishes. Relative levels of VgA and VgB mRNAs were low in April, increased
      significantly during the reproductive period in May and June, and declined in
      July. There was a trend towards higher relative levels of VgA and VgB mRNAs in
      captive fish compared to wild individuals during the reproductive period. The
      surface occupied by eosinophilic yolk granules in fully vitellogenic oocytes, as
      well as the frequency of oocytes in late vitellogenesis, was significantly higher
      in captive compared to wild individuals. The study suggests that the experimental
      conditions under which Atlantic bluefin tuna individuals were reared allowed the
      occurrence of normal vitellogenesis, based on gene expression of VgA and VgB in
      the liver and yolk accumulation in the oocytes. The higher yolk accumulation and
      frequency of vitellogenic oocytes observed in the ovaries of captive fish suggest
      that improvements in feeding practices may result in an improved vitellogenic
      process.

PMID- 21093996
TI  - Dementia care in rural and remote settings: a systematic review of
      informal/family caregiving.
AB  - OBJECTIVES: The purpose of this review is to critically evaluate the available
      evidence from the published scientific literature on informal/family dementia
      care in rural and remote settings to assess the current state of knowledge,
      identify support implications, and make recommendations for future research.
      METHODS: A systemic review of the literature indexed in ISI Web of Knowledge,
      PsychInfo, Medline, Healthstar, CINAHL, EMBASE, and Sociological Abstracts was
      conducted. Data were extracted from papers meeting inclusion criteria: peer
      reviewed papers that focused on dementia or Alzheimer's Disease (AD), and
      examined informal or family caregiving in relation to persons with AD or dementia
      in remote or rural locations. RESULTS: The search identified 872 articles for
      review, reduced to 72 after removing duplicates and articles not meeting
      inclusion criteria. Of the 72 remaining, 26 are included in this review focusing
      on informal/family caregiving. A previous review focused on the 46 studies on
      formal/paid care. Four themes that correspond to the current state of knowledge
      about rural informal/family dementia caregiving in the 26 included studies were:
      service use, carer experience, support and education, and rural perceptions of
      dementia. CONCLUSIONS: Despite the growing body of evidence over the 20 years of
      this review, and the widespread interest in family dementia caregiving generally,
      much of the research exploring family caregiving in rural areas focuses on the
      experience, use and barriers to formal service provision. There is limited work
      examining the experiences of rural caregivers and their education and support
      needs. More research is needed about the impact of rurality on caregiving and the
      education and support needs of rural informal family caregivers.

PMID- 21093995
TI  - Phase III data for abiraterone in an evolving landscape for castration-resistant
      prostate cancer.
AB  - At the 2010 meeting of the European Society for Medical Oncology (ESMO), a
      landmark development in prostate cancer therapy was unveiled. In a phase III
      study, the CYP17 inhibitor abiraterone yielded a survival advantage over placebo
      in patients with metastatic castration-resistant prostate cancer (mCRPC) who had
      progressed despite prior docetaxel therapy. The data for abiraterone follow the
      publication of successful phase III studies earlier this year supporting two
      mechanistically distinct agents-namely, the novel taxane cabazitaxel and the
      autologous dendritic cell vaccine sipuleucel-T. A challenge that lies ahead for
      the scientific community is to discern the appropriate positioning of abiraterone
      in an increasingly crowded therapeutic landscape. Several ongoing trials are
      examining the agent in earlier settings (i.e., a phase III in mCRPC pre
      docetaxel, and smaller studies in combination with radiation therapy or as
      neoadjuvant pre-surgery for localized disease). Herein, several potential
      strategies for abiraterone are presented to clarify the clinical utilization of
      this agent in the future.

PMID- 21093997
TI  - Carbon monoxide concentrations in the 2009 Victorian Bushfire disaster victims.
AB  - Blood was available for the estimation of carboxyhemoglobin saturation (COHb) in
      30 of the 173 persons who died in the Victorian bushfires in February 2009. The
      ages of these 30 deaths ranged from 3 to 80 years and there were 8 females. 13
      cases (43%) were considered negative (less than 5% COHb), 12 (40%) were between 5
      and 40% COHb, 2 (6.7%) between 40 and 50% and 3 (10%) were greater than 50% COHb.
      There were 6 persons either found within a building or a car and the COHb in
      these cases ranged up to 69% (mean 50%). There were 5 cases where the location
      was unable to be determined as either indoor or outdoor due to the extensive
      nature of the fire. The remaining 19 deceased persons were all located outside in
      the open and the concentration of COHb in these cases ranged up to 30% (mean
      19%). Hydrogen cyanide was only detected in two deceased persons at
      concentrations of 0.5 and 2.7 mg/L, respectively. 13 deceased were found to have
      soot in the airways following necropsy but this did not correlate with the COHb
      levels.

PMID- 21093998
TI  - Study of TATP: stability of TATP solutions.
AB  - Stability of raw TATP (3,3,6,6,9,9-hexamethyl-1,2,4,5,7,8-hexoxonane) samples in
      solutions of common solvents was studied to highlight problems faced by forensic
      labs in identification and analysis of organic peroxide samples. The TATP samples
      were prepared by reaction of acetone and hydrogen peroxide (30%) with the aid of
      following catalysts: hydrochloric, sulfuric, nitric, perchloric and
      methanesulfonic acid. Acetone, acetonitrile, methanol and acetonitrile/water
      solutions of TATP samples were prepared and stored at 50 degrees C. Various
      degrees of stability were observed for particular combination of catalyst and
      solvent ranging from totally unstable (catalyst-H(2)SO(4)/any solvent) to very
      stable (catalyst-HCl/solvent acetonitrile). Purification of crude TATP by re
      crystallization results in product stable in all investigated solvents. Stability
      of solution prepared from re-crystallized DADP (3,3,6,6-tetramethyl-1,2,4,5
      tetroxane) was found to be on the same level as the stability of solution of re
      crystallized TATP.

PMID- 21093999
TI  - Glomangiopericytoma of the nasal cavity.
AB  - Glomangiopericytoma is a rare tumor arising from the pericytes surrounding
      capillaries, and accounts for less than 0.5% of all sinonasal tumors. A 60-year
      old male patient presented with a glomangiopericytoma of the nasal cavity
      manifesting as nasal obstruction and epistaxis, which was treated successfully
      with endoscopic excision. Histological examination showed multiplication of
      spindle-shaped to oval cells which reacted strongly to immunostaining for alpha
      smooth muscle actin. Glomangiopericytoma is categorized as a borderline low
      malignancy tumor, which tends to recurrence. Strict follow-up is required,
      especially if complete resection is not achieved.

PMID- 21094000
TI  - Prevalence of eating disorders symptoms in nonelite ballet dancers and basketball
      players: An exploratory and controlled study among French adolescent girls.
AB  - BACKGROUND: Until recently, very few controlled studies have examined the
      prevalence of eating disorders (ED) symptoms among nonelite adolescent female
      athletes. Moreover, results are mixed and inconclusive. Therefore, the aim of
      this exploratory study was to examine the prevalence of ED symptoms (underweight,
      bulimia, drive for thinness, body dissatisfaction) among French nonelite
      adolescent female athletes (ballet dancers and basketball players) and
      nonathletes. METHOD: The sample of adolescent girls (aged between 12 and 16
      years), consisted of 43 basketball players, 52 ballet dancers and 49 nonathlete
      controls. The eating disorder inventory and a demographic-personal information
      questionnaire (date of birth, experience of ED, week training time, etc.) were
      filled out by the participants. Additionally, all participants were measured and
      weighed. The frequencies of ED symptoms were compared between the groups
      (athletes versus nonathletes, ballet dancers versus basketball players) using a
      series of chi2 tests. RESULTS: The chi2 tests did not show significant
      differences in frequencies of underweight and body dissatisfaction symptoms
      between nonelite athletes and nonathletes. However, results highlighted a
      nonsignificant trend toward higher frequency of: (i) drive for thinness (P=0.05)
      symptoms in nonelite athletes compared with nonathletes, and (ii) bulimia
      (P=0.06) symptoms in nonathletes compared with nonelite athletes. Additional
      analyses performed among the sport groups revealed that the prevalence of drive
      for thinness symptoms was significantly two-fold higher in ballet dancers than
      basketball players (34.6% versus 16.3%). Nevertheless, no significant differences
      were found in the frequencies of underweight, bulimia and body dissatisfaction
      symptoms among the sport groups. CONCLUSION: This study showed that the frequency
      of ED symptoms is equivalent in nonelite athletes and nonathletes. However, these
      nonsignificant results should be interpreted with caution regarding the weak
      statistical power of the analyses and the small sample size. Detailed analysis
      revealed a significantly higher prevalence of drive for thinness symptoms in
      ballet dancers in comparison with basketball players. Consequently, these results
      should be viewed as preliminary and further studies are needed before they can be
      generalized to French adolescent female athletes.

PMID- 21094001
TI  - [Burden of herpes zoster and postherpetic neuralgia: Incidence, proportion, and
      associated costs in the French population aged 50 or over].
AB  - BACKGROUND: Despite the perspective of vaccination against herpes zoster, there
      are few recent data available on the incidence of this disease, the proportion of
      postherpetic neuralgia cases, and associated disease management costs. This study
      was performed to evaluate these parameters in a representative sample of French
      physicians. METHODS: It was a retrospective, declarative study conducted from the
      medical files of patients who presented with herpes zoster and consulted in 2005,
      based on a random sample of GPs, dermatologists, neurologists, and physicians in
      pain clinics, weighted by demographic departmental distribution of patients aged
      50 years and above. The analysis was performed on cases diagnosed by physicians
      themselves (incident cases). RESULTS: The annual incidence of herpes zoster was
      estimated at 8.99/1000 [8.34-9.64], all types of physicians pooled and at
      8.67/1000 for GPs. This represents about 182,500 cases of herpes zoster in France
      in 2005 in patients aged 50 years and above. Incidence was slightly higher
      amongst women (1.3 times) and increased with age. Amongst the 777 cases of
      incident herpes zoster, 343 were complicated by postherpetic neuralgia one month
      after diagnosis. The proportion of patients presenting postherpetic neuralgia at
      3 and 6 months was 32.1% and 17.6%, respectively. The annual cost of management
      of herpes zoster and postherpetic neuralgia was estimated at 170 [109-249]
      million euros, of which 61.0 million euros were covered by the national health
      insurance. CONCLUSION: In this study, the incidence of herpes zoster observed in
      France in subjects aged 50 years and above is close to that already estimated in
      France and Europe. The proportion of postherpetic neuralgia is high and this
      painful complication may persist for several months after diagnosis of herpes
      zoster. To our knowledge, EPIZOD is the first study conducted in France to assess
      the cost of herpes zoster and of postherpetic neuralgia, the most frequent
      complication of this viral disease.

PMID- 21094002
TI  - [Reliability of anthropometric measurements performed by community nutrition
      workers in a community-based pediatric growth-monitoring program in rural
      Rwanda].
AB  - BACKGROUND: In Rwanda, the community-based growth-monitoring program is
      implemented via volunteer community nutrition workers. These volunteers are
      recruited from within their communities, and receive basic training prior to
      providing services. Utilizing local volunteers improves access to basic nutrition
      services, and allows the local health jurisdictions to use qualified health care
      staff more efficiently. In addition to concerns raised in regards to the
      accountability of unpaid workers, some question the relevance of the data that is
      collected. We carried out a nutritional survey in the catchment area of Ruli
      District Hospital to evaluate the reliability of the community nutrition workers'
      measurements of anthropometric standards collected within the growth-monitoring
      framework. METHODS: A nutritional survey was recently organized in the catchment
      area of the hospital in December 2006. The prevalence rates of malnutrition from
      the survey were compared with those from the existing community-based growth
      monitoring program. Z-test was used to compare the prevalence rate of underweight
      from the survey with the prevalence rate determined by data collected from
      community nutrition workers. The concordance of children classified with moderate
      and severe underweight in each data set was determined by the coefficient Kappa
      of Cohen. RESULTS: Our findings show that the recent survey reported an overall
      underweight prevalence rate of 27.2%. Community data calculated a prevalence rate
      of 28.8% for the same population. The difference is not statistically significant
      (P=0.294). Of 724 children evaluated, the survey and the community were in
      agreement in regards to 454 children classified in the category of good
      nutritional status, 143 children classified in moderate underweight and 11
      children classified in the severe underweight category. The Kappa of Cohen
      coefficient of 0.636 indicates strong concordance between data sets. CONCLUSION:
      Anthropometric measurements provided by the community are reliable. Information
      gathered from the community can be used for epidemiologic monitoring of
      malnutrition. To ensure continued reliability, health centers must provide
      sufficient and permanent training to community nutrition workers. In addition,
      continued access to essential materials used for measuring nutritional status and
      maintenance of these materials will be crucial to the program's ongoing success.

PMID- 21094003
TI  - [Burnout among mental health professionals: A Tunisian experience].
AB  - BACKGROUND: Burnout syndrome consists in physical as well as mental exhaustion
      observed in professionals whose work involves continuous contact with other
      people. Psychiatrists and psychiatry nursing staff are considered to be
      vulnerable to experiencing burnout. The purposes of this study aim to investigate
      the prevalence of burnout syndrome in practitioners, residents and nurses working
      in the psychiatric hospital of Tunisia. It also aims to investigate the
      relationship between burnout, depression, and a variety of personal variables,
      including age, gender, marital, parental and personal difficulties within this
      population. METHODS: A cross-sectional study was conducted among the nursing
      staff (n=54), residents (n=41) and practitioners (n=11) in Razi hospital in
      Tunisia. The Maslach Burnout Inventory, the Beck depression inventory and a
      general questionnaire on demographic data were used. RESULTS: High levels of
      burnout were detected among nurses. This was true for the emotional tiredness sub
      scale (mean score: 26.18); the depersonalization subscale (mean score: 10.20) and
      for the alteration of personal achievements (mean score: 32.94). High scores in
      emotional tiredness were correlated to depression (P=0.000; R=0.56) and to
      personal difficulties (P=0.021; R=0.31) in this group. Residents showed high
      scores in personal achievements (mean score: 32.56), and practitioners did not
      reach the cutoff scores on the Maslach Burnout Inventory. CONCLUSION: Our results
      are somewhat comparable to those of studies in other countries. Burnout syndrome
      was highly prevalent among nurses and residents. This study corroborates former
      results of a relation between depression and burnout. A strong relationship was
      found between personal difficulties and burnout, but seemed to be more specific
      to the nursing sample.

PMID- 21094004
TI  - [The case series method].
AB  - The case series method was developed by Farrington (1995) to investigate the
      strength of association between a time-varying exposure and an acute rare
      potentially recurrent event, using cases only. It can be used when the exposure
      can only be causally related to the event during a limited period of time. It has
      been widely used in pharmaco-epidemiology, particularly in the study of vaccine
      safety. The method is derived from a Poisson model by conditioning on the
      individual total number of events and its exposure history. As a consequence of
      this conditioning, the effects of fixed covariates cancel out, so that the method
      has a particular advantage as compared with cohort and case-control studies.

PMID- 21094005
TI  - [Bacterial resistance and antibiotic prescriptions: perceptions, attitudes and
      knowledge of a sample of French GPs].
AB  - OBJECTIVE: The study's objective was to assess General Practitioners' (GPs)
      perceptions of their antibiotic prescribing practice and of bacterial resistance.
      DESIGN: We surveyed a random sample of 102 GPs out of the 1242 working in the
      Alpes-Maritimes area (France). RESULTS: The response rate was 69%. More than 80%
      of the GPs felt confident when prescribing an antibiotic. The two main factors
      thought to influence their antibiotic prescriptions were their previous
      experience (97%) and guidelines (81%), advice from a colleague was quoted by only
      13% of the GPs. Antibiotic resistance was perceived as a national problem by 91%
      of the respondents, but only 65% rated the problem as important in their own
      daily practice. Widespread and inappropriate antibiotic use, prescription of
      broad spectrum antibiotics or too low antibiotic doses were rated as important
      causes of resistance, but excessive duration of antibiotic treatment or poor hand
      hygiene practices were cited less often. The three measures perceived to be
      helpful or very helpful to improve antibiotic prescribing by more than 80% of the
      GPs were training sessions, availability of guidelines and of resistance data.
      CONCLUSIONS: These perceptions must be taken into account to maximize adherence
      of GPs to the measures intended to limit bacterial resistance.

PMID- 21094006
TI  - [A combination of intramedullary tuberculoma, brain tuberculomas, miliary
      pulmonary and hematologic tuberculosis].

PMID- 21094007
TI  - [A case of Pseudomonas mendocina endocarditis].

PMID- 21094008
TI  - [Quick recovery, after administration of a botulinic antitoxin serum in two
      patients presenting with botulism].

PMID- 21094010
TI  - Semi-automated volumetric analysis of artificial lymph nodes in a phantom study.
AB  - PURPOSE: Quantification of tumour burden in oncology requires accurate and
      reproducible image evaluation. The current standard is one-dimensional
      measurement (e.g. RECIST) with inherent disadvantages. Volumetric analysis is
      discussed as an alternative for therapy monitoring of lung and liver metastases.
      The aim of this study was to investigate the accuracy of semi-automated
      volumetric analysis of artificial lymph node metastases in a phantom study.
      MATERIALS AND METHODS: Fifty artificial lymph nodes were produced in a size range
      from 10 to 55mm; some of them enhanced using iodine contrast media. All nodules
      were placed in an artificial chest phantom (artiCHEST(r)) within different
      surrounding tissues. MDCT was performed using different collimations (1-5 mm) at
      varying reconstruction kernels (B20f, B40f, B60f). Volume and RECIST measurements
      were performed using Oncology Software (Siemens Healthcare, Forchheim, Germany)
      and were compared to reference volume and diameter by calculating absolute
      percentage errors. RESULTS: The software performance allowed a robust volumetric
      analysis in a phantom setting. Unsatisfying segmentation results were frequently
      found for native nodules within surrounding muscle. The absolute percentage error
      (APE) for volumetric analysis varied between 0.01 and 225%. No significant
      differences were seen between different reconstruction kernels. The most
      unsatisfactory segmentation results occurred in higher slice thickness (4 and 5
      mm). Contrast enhanced lymph nodes showed better segmentation results by trend.
      CONCLUSION: The semi-automated 3D-volumetric analysis software tool allows a
      reliable and convenient segmentation of artificial lymph nodes in a phantom
      setting. Lymph nodes adjacent to tissue of similar density cause segmentation
      problems. For volumetric analysis of lymph node metastases in clinical routine a
      slice thickness of <=3mm and a medium soft reconstruction kernel (e.g. B40f for
      Siemens scan systems) may be a suitable compromise for semi-automated volumetric
      analysis.

PMID- 21094009
TI  - Ganglia of the tarsal sinus: MR imaging features and clinical findings.
AB  - PURPOSE: To analyze MR imaging and clinical findings associated with ganglia of
      the tarsal sinus. MATERIALS AND METHODS: In a record search, ganglia of the
      tarsal sinus were retrospectively identified in 26 patients (mean age 48+/-16
      years), who underwent MR imaging for chronic ankle pain. Images were reviewed by
      two radiologists in consensus for size and location of ganglia, lesions of
      ligaments of the ankle and the tarsal sinus, tendon abnormalities,
      osteoarthritis, osseous erosions and bone marrow abnormalities. Medical records
      were reviewed for patient history and clinical findings. RESULTS: Ganglia were
      associated with the interosseus ligament in 81%, the cervical ligament in 31% and
      the retinacula in 46% of cases. Signal alterations suggesting degeneration were
      found in 85%, 50% and 63% in case of the interosseus ligament, the cervical
      ligament and the retinacula, respectively. Scarring of the anterior talofibular
      ligament and the fibulocalcaneal ligament was found in 68% and 72% of the
      patients, respectively, while only 27% of the patients recalled ankle sprains.
      Ganglia at the retinacula were highly associated with synovitis and tendinosis of
      the posterior tibial tendon (p<0.05). CONCLUSION: All patients with ganglia in
      the tarsal sinus presented with another pathology at the ankle, suggesting that
      degeneration of the tarsal sinus may be a secondary phenomenon, due to pathologic
      biomechanics at another site of the hind foot. Thus, in patients with
      degenerative changes of the tarsal sinus, one should be alerted and search for
      underlying pathology, which may be injury of the lateral collateral ligaments in
      up to 70%.

PMID- 21094011
TI  - Metabolic profiling of GuanXin II prescription based on metabolic fingerprinting
      and chemical analysis.
AB  - A sensitive LC/MS method was established to investigate the in vivo metabolism of
      GuanXin II prescription, a five-component Chinese herbal medicine formulation.
      Rat plasma, bile, urine, and feces were collected and analyzed following oral
      administration of the water decoction. A total of 50 compounds were identified,
      including 17 prototypes and 33 metabolites underwent methylation, oxidation,
      hydrolysis, sulfate conjugation, glucuronide conjugation, and glutathion
      conjugation. In addition, the component herb of the formulation from which the
      metabolites were derived was also identified. Among the five component herbs,
      Rhizoma Chuanxiong, Flos Carthami, and Lignum Dalbergiae Odoriferae were actively
      metabolized, contributing 26 metabolites and 2 prototypes, while Radix Salviae
      Miltiorrhizae and Radix Paeoniae Rubra underwent less biotransformation, yielding
      7 metabolites and 15 prototypes. This is the first study on the metabolic profile
      of GuanXin II prescription. The results could be valuable to elucidate the
      material basis of this formulated Chinese medicine.

PMID- 21094012
TI  - Defenses to malpractice: what every emergency physician should know.
AB  - BACKGROUND: Emergency medicine is a high-risk specialty that carries a constant
      risk of malpractice litigation. Fear of malpractice litigation can lead to less
      than-optimal patient care as well as impairments in physician quality of life.
      Although malpractice fear can be ubiquitous among emergency physicians, most
      receive little to no education on malpractice. DISCUSSION: Medical malpractice
      requires that 1) The physician had a duty, 2) The physician breached the duty, 3)
      There was harm to the patient, and 4) The harm was caused by the physician's
      breach of duty. Even if all four medical malpractice conditions are met, there
      are still special legal defenses that have been and can be used in court to
      exonerate the physician. These defenses include assumption of the risk, Good
      Samaritan, contributory negligence, comparative fault, sudden emergency,
      respectable minority, two schools of thought, and clinical innovation.
      CONCLUSIONS: These legal defenses are illustrated and explained using defining
      precedent cases as well as hypothetical examples that are directly applicable to
      emergency medical practice. Knowledge of these special legal defenses can help
      emergency physicians minimize their risk of litigation when caring for patients.

PMID- 21094013
TI  - 'Talking of Sex': developing and piloting a sexual health communication tool for
      use in primary care.
AB  - OBJECTIVE: To develop and pilot a communication aid aimed at increasing the
      frequency with which sexual health issues are raised proactively with young
      people in primary care. METHODS: Group interviews among primary health care
      professionals to guide development of the tool, simulated consultations to pre
      test it, and a pilot study to assess effectiveness. RESULTS: We developed an
      electronic consultation aid: Talking of Sex and piloted it in eight general
      practices across the UK. 188 patients and 58 practitioners completed
      questionnaires pre-intervention, and 92 patients and 45 practitioners post
      intervention. There was a modest increase in the proportion of consultations in
      which sexual health was raised, from 28.1% pre-intervention to 32.6% post
      intervention. In consultations with nurses the rise was more marked. More
      patients reported discussing preventive practices such as condom use post
      intervention. Patients unanimously welcomed the opportunity to discuss sexual
      health matters with their practitioner. CONCLUSION: The tool has capacity to
      increase the frequency with which sexual health is raised in primary care,
      particularly by nurses, to influence the topics discussed, and to improve patient
      satisfaction. PRACTICE IMPLICATIONS: The tool has potential in increasing the
      proportion of young people whose sexual health needs are addressed in general
      practice.

PMID- 21094014
TI  - Extending the reach, effectiveness, and efficiency of communication: evidence
      from the centers of excellence in cancer communication research.

PMID- 21094015
TI  - Teaching physicians to address unhealthy alcohol use: a randomized controlled
      trial assessing the effect of a Web-based module on medical student performance.
AB  - BACKGROUND: The authors developed and evaluated an interactive, Web-based module
      to train medical students in screening and brief intervention (SBI) for unhealthy
      alcohol use. METHODS: First-year students were randomized to module versus
      lecture. Change in knowledge, attitudes, and confidence were compared.
      Performance was assessed by objective structured clinical examination (OSCE) and
      analyzed by intention to treat and treatment received. RESULTS: Of 141 consenting
      students, 64% (n = 90) completed an intervention (54% lecture vs. 70% Web
      assigned). Knowledge, confidence, and attitudes improved in both groups, with
      more improvement in Advise-Assist knowledge for Web students (14% vs. -3%, p =
      .003). Web students outperformed their lecture peers in both general
      communication (65% vs. 51% items well done, p = .004) and alcohol-specific tasks
      (54% vs. 41%, p = .021) on OSCE. Analysis by treatment received enhanced between
      group differences. CONCLUSION: Use of a Web-based module to teach SBI is
      associated with greater knowledge gain and skills performance compared with a
      lecture covering similar content. The module provides an efficient means for
      training in this area.

PMID- 21094016
TI  - Prognostic relevance of the lymph node ratio in surgical patients with
      extrahepatic cholangiocarcinoma.
AB  - AIM: Few studies have investigated the influence of the lymph node ratio (LNR),
      the ratio of the number of lymph nodes harboring metastatic cancer to the total
      number of lymph nodes removed, on the outcome after surgery for extrahepatic
      cholangiocarcinoma. This study was conducted to examine the prognostic impact of
      LNR in patients undergoing resection for extrahepatic cholangiocarcinoma.
      PATIENTS AND METHODS: We retrospectively analyzed a total of 60 consecutive
      patients who underwent resection for extrahepatic cholangiocarcinoma. We focused
      on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13
      patients, and greater than 0.2 in 13 patients. RESULTS: The overall five-year
      survival rates for patients with LNRs of 0, 0 to 0.2, and >=0.2 were 44%, 10%,
      and 0%, respectively (p = 0.023). LNR was an independent predictive factor for
      estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022)
      analyses including LNR, the sites of the primary tumors, and surgical margin as
      the variables. There were no statistically significant differences between
      patients who had less than 12 lymph nodes removed and those who had 12 or more
      lymph nodes removed (p = 0.484). CONCLUSION: LNR was a powerful, independent
      predictor of estimated survival in patients undergoing surgical resection for
      extrahepatic cholangiocarcinoma. LNR should be considered when stratifying
      patients for future clinical trials.

PMID- 21094017
TI  - [Management of aortic dissection. Stent grafts for who?].
AB  - Acute aortic syndrome (AAS) describes several life threatening aortic
      pathologies. Acute aortic syndrome include intramural haematoma, penetrating
      aortic ulcer and acute aortic dissection. Advances in both imaging and
      endovascular treatment has led to an increase in diagnosis and improved
      management of these often catastrophic pathologies. The current place of stent
      grafts for the AAS management is defined on the basis of the most recent
      literature.

PMID- 21094019
TI  - Relational treatment strategies increase social approach behaviors in patients
      with Generalized Social Anxiety Disorder.
AB  - We incorporated strategies based on relational and interpersonal circumplex
      research within a standard cognitive-behavioral regimen for Generalized Social
      Anxiety Disorder (GSAD, Generalized Social Phobia) to determine whether these
      techniques increased the social approach behaviors that facilitate relationship
      development. Individuals seeking treatment for GSAD were randomly assigned to
      either the integrated interpersonal cognitive-behavioral group treatment (ICBT)
      or a wait list condition (WL). Results revealed that the interpersonal techniques
      were readily implemented by the majority of patients. ICBT produced significant
      increases in frequency of social approach behaviors and relationship
      satisfaction, in addition to GSAD symptom reductions comparable to other group
      CBT regimens. The current research highlights the feasibility and potential
      benefit of incorporating strategies based on relational and circumplex theories
      into cognitive-behavioral regimens for GSAD.

PMID- 21094018
TI  - Development of a composite pain measure for persons with advanced dementia:
      exploratory analyses in self-reporting nursing home residents.
AB  - CONTEXT: Experts agree that pain assessment in noncommunicative persons requires
      data from sources that do not rely on self-report, including proxy reports,
      health history, and observation of pain behaviors. However, there is little
      empirical evidence to guide clinicians in weighting or combining these sources to
      best approximate the person's experience. OBJECTIVES: The aim of this exploratory
      study was to identify a combination of observer-dependent pain indicators that
      would be significantly more predictive of self-reported pain intensity than any
      single indicator. Because self-reported pain is usually viewed as the criterion
      measure for pain, self-reported usual and worst pains were the dependent
      variables. METHODS: The sample consisted of 326 residents (mean age: 83.2 years;
      69% female) living in one of 24 nursing homes. Independent variables did not rely
      on self-report: surrogate reports from certified nursing assistants (CNAs) using
      the Iowa Pain Thermometer (IPT), Checklist of Nonverbal Pain Indicators (CNPI),
      Cornell Scale for Depression in Dementia (CSDD), Pittsburgh Agitation Scale
      (PAS), number of painful diagnoses, and Minimum Data Set (MDS) pain variables.
      RESULTS: In univariate analyses, the CNA IPT scores were correlated most highly
      with self-reported pain. The final multivariate model for self-reported usual
      pain included CNA IPT, CSDD, PAS, and education; this model accounted for only
      14% of the variance. The more extensive of the two final models for worst pain
      included MDS pain frequency, CSDD, CNA IPT, CNPI, and age (R(2)=0.14).
      CONCLUSION: Additional research is needed to develop a predictive pain model for
      nonverbal persons.

PMID- 21094021
TI  - Evidence for a unique PTSD construct represented by PTSD's D1-D3 symptoms.
AB  - Two models of posttraumatic stress disorder (PTSD) have received the most
      empirical support in confirmatory factor analytic studies: King, Leskin, King,
      and Weathers' (1998) Emotional Numbing model of reexperiencing, avoidance,
      emotional numbing and hyperarousal; and Simms, Watson, and Doebbeling's (2002)
      Dysphoria model of reexperiencing, avoidance, dysphoria and hyperarousal. These
      models only differ in placement of three PTSD symptoms: sleep problems (D1),
      irritability (D2), and concentration problems (D3). In the present study, we
      recruited 252 women victims of domestic violence and tested whether there is
      empirical support to separate these three PTSD symptoms into a fifth factor,
      while retaining the Emotional Numbing and Dysphoria models' remaining four
      factors. Confirmatory factor analytic findings demonstrated that separating the
      three symptoms into a separate factor significantly enhanced model fit for the
      Emotional Numbing and Dysphoria models. These three symptoms may represent a
      unique latent construct. Implications are discussed.

PMID- 21094020
TI  - The prevalence and clinical implications of self-medication among individuals
      with anxiety disorders.
AB  - Alcohol dependence (AD) is more likely to occur among individuals with rather
      than without an anxiety disorder. Self-medication theory (SMT) holds that
      drinking behavior is negatively reinforced when alcohol temporarily reduces
      anxiety and that the resulting escalation of drinking increases the risk for AD.
      We set out to empirically scrutinize SMT using the National Epidemiologic Survey
      on Alcohol and Related Conditions (NESARC) dataset. We found that only a minority
      (about 20%) of anxiety disordered individuals endorsed drinking to control
      anxiety symptoms. This minority drank more alcohol, had a higher cross-sectional
      rate of AD, and was at higher risk for developing new AD over four years compared
      to anxiety disordered non-self-medicators and individuals with no anxiety
      disorder. Consistent with SMT, increased prospective risk for AD among self
      medicators is partially mediated by an increased level of alcohol use.
      Understanding the processes that promote and inhibit self-medication should be a
      priority for anxiety disorder researchers.

PMID- 21094022
TI  - Searching the sky with CONFIGR-STARS.
AB  - CONFIGR-STARS, a new methodology based on a model of the human visual system, is
      developed for registration of star images. The algorithm first applies CONFIGR, a
      neural model that connects sparse and noisy image components. CONFIGR produces a
      web of connections between stars in a reference starmap or in a test patch of
      unknown location. CONFIGR-STARS splits the resulting, typically highly connected,
      web into clusters, or "constellations". Cluster geometry is encoded as a
      signature vector that records edge lengths and angles relative to the cluster's
      baseline edge. The location of a test patch cluster is identified by comparing
      its signature to signatures in the codebook of a reference starmap, where cluster
      locations are known. Simulations demonstrate robust performance in spite of image
      perturbations and omissions, and across starmaps from different sources and
      seasons. Further studies would test CONFIGR-STARS and algorithm variations
      applied to very large starmaps and to other technologies that may employ
      geometric signatures. Open-source code, data, and demos are available from
      http://techlab.bu.edu/STARS/.

PMID- 21094023
TI  - Some comparisons of complexity in dictionary-based and linear computational
      models.
AB  - Neural networks provide a more flexible approximation of functions than
      traditional linear regression. In the latter, one can only adjust the
      coefficients in linear combinations of fixed sets of functions, such as
      orthogonal polynomials or Hermite functions, while for neural networks, one may
      also adjust the parameters of the functions which are being combined. However,
      some useful properties of linear approximators (such as uniqueness, homogeneity,
      and continuity of best approximation operators) are not satisfied by neural
      networks. Moreover, optimization of parameters in neural networks becomes more
      difficult than in linear regression. Experimental results suggest that these
      drawbacks of neural networks are offset by substantially lower model complexity,
      allowing accuracy of approximation even in high-dimensional cases. We give some
      theoretical results comparing requirements on model complexity for two types of
      approximators, the traditional linear ones and so called variable-basis types,
      which include neural networks, radial, and kernel models. We compare upper bounds
      on worst-case errors in variable-basis approximation with lower bounds on such
      errors for any linear approximator. Using methods from nonlinear approximation
      and integral representations tailored to computational units, we describe some
      cases where neural networks outperform any linear approximator.

PMID- 21094024
TI  - Friction heat during self-drilling of an orthodontic miniscrew.
AB  - The aim of this study was to measure the heat generated when using a self
      drilling miniscrew at speeds of 50, 100, 150, and 250 rpm. Specimens were
      classified into two groups: in the thin group the cortical bone thickness was 1.2
      +/- 0.02 mm on average and in the thick group it was 2.0 +/- 0.03 mm on average.
      The thin group was used to model maxillary bone and the thick group to model
      mandibular bone in humans. The temperature in the 1.2-mm and 2.0-mm cortical bone
      specimens was measured according to revolution speed. As the revolution speed
      increased, the temperature significantly increased in both bone thicknesses. The
      temperature increased significantly more in the thicker cortical bone. The
      temperature increase in the 2.0-mm thick bone at 250 rpm exceeded 10 degrees C,
      regarded as the threshold for bone damage in this study; other temperature
      increases were below this threshold. Installing self-drilling screws at high
      speeds with an implanter is not recommended; low speeds of less than 150 rpm
      should be used.

PMID- 21094025
TI  - A randomized, controlled trial of computer-assisted cognitive remediation for
      schizophrenia.
AB  - OBJECTIVE: There is considerable interest in cognitive remediation for
      schizophrenia. Our study aimed to evaluate, in a large sample of patients with
      schizophrenia, the interest of a computer-assisted cognitive remediation program
      on cognitive performances of patients as well as in clinical and functional
      outcome. METHOD: Seventy-seven patients with remitted schizophrenia were randomly
      assigned to 14 2-hours individual sessions of computer-assisted cognitive
      remediation (n=39) or a control condition (n=38). Remediation was performed using
      RehaCom (r) software. Four procedures were chosen to train four cognitive
      functions involved in different stages of the information processing:
      attention/concentration, working memory, logic, and executive functions. Primary
      outcomes were remediation exercise metrics, neuropsychological composites
      (episodic memory, working memory, attention, executive functioning, and
      processing speed), clinical and community functioning measures. RESULTS:
      Cognitive performances concerning Attention/vigilance, verbal working memory and
      verbal learning memory and reasoning/problem solving improved significantly in
      the remediation condition when no difference was reported in the control
      condition between the 2 assessments. However, there were no significant benefits
      of cognitive remediation on non-verbal working memory and learning and speed of
      processing or functional outcome measures. CONCLUSIONS: Cognitive remediation for
      people with schizophrenia was effective in improving performance, but the
      benefits of training did not generalize to functional outcome measures. Long term
      follow-up studies are needed to confirm the maintenance of such improvements.

PMID- 21094026
TI  - DNA condensations on mica surfaces induced collaboratively by alcohol and
      hexammine cobalt.
AB  - We performed systematic studies of lambda-DNA condensation on mica surfaces
      induced by alcohol and hexammine cobalt (III) [Co(NH(3))(6)(3+)] using atomic
      force microscopy (AFM). The critical condensation concentration for
      [Co(NH(3))(6)(3+)] was found to be about 10 microM; the DNA molecules extended
      freely on mica when the concentration was below the critical value. The
      morphology of condensed DNA became more compact with increasing concentration. At
      about 500 microM [Co(NH(3))(6)(3+)] concentration, no condensation patterns could
      be observed due to charge inversion of the compact structures resulting in
      failure of adhesion to the positively charged surfaces. The critical
      concentration for alcohol was about 15% (v/v). At this concentration, a few
      intramolecular loops could be observed in the AFM images. With increasing ethanol
      concentration the condensation pattern became more complicated ranging from
      flower-like to pancake-like. When the solution contained both alcohol and
      hexammine cobalt (III), DNA condensation patterns could be observed even when the
      concentrations of the two condensation agents were lower than their critical
      values. We observed this phenomenon by adding mixtures of 10% alcohol and 8
      microM hexammine cobalt (III) to DNA solutions. The condensation patterns were
      more compact than those of the condensation agents separately. Typical toroids
      were found at an appropriate alcohol and hexammine cobalt (III) concentration.
      The collaborative condensation phenomenon was analyzed by electrostatic
      interaction and charge neutralization.

PMID- 21094027
TI  - Fluorine-18 deoxyglucose positron emission tomography, magnetic resonance imaging
      and bone scintigraphy for the diagnosis of bone metastases in patients with lung
      cancer: which one is the best?--a meta-analysis.
AB  - AIMS: To carry out a meta-analysis to compare fluorine-18 deoxyglucose ((18)FDG)
      positron emission tomography (PET), magnetic resonance imaging (MRI) and bone
      scintigraphy imaging for the diagnosis of bone metastases in patients with lung
      cancer. MATERIALS AND METHODS: MEDLINE, EMBASE, Scopus and other databases were
      searched for relevant original articles published between January 1995 and
      January 2010. Inclusion criteria were as follows: (18)FDG PET, MRI or (99m)Tc-MDP
      bone scintigraphy was carried out to detect bone metastases in patients with lung
      cancer; sufficient data were presented to construct a 2*2 contingency table;
      histopathological analysis and/or close clinical and imaging follow-up and/or
      radiographic confirmation by multiple imaging modalities were used as the
      reference standard. Two reviewers independently extracted data. META-DiSc was
      used to obtain pooled estimates of sensitivity, specificity, diagnostic odds
      ratio (DOR), summary receiver operating characteristic (SROC) curves and the *Q
      index. RESULTS: In total, 14 articles that consisted of 34 studies fulfilled all
      inclusion criteria. On a per-patient basis, the pooled sensitivity estimates for
      PET, MRI and bone scintigraphy were 91.9, 80.0 and 91.8%, respectively. The
      sensitivity for PET and bone scintigraphy were significantly higher than for MRI
      (P<0.05). There was no significant difference between PET and bone scintigraphy
      (P>0.05). The pooled specificity estimates for PET, MRI and bone scintigraphy
      were 96.8, 90.6 and 68.8%, respectively. The specificity for PET was
      significantly higher than for MRI and bone scintigraphy (P<0.05), and the
      specificity for MRI was significantly higher than for bone scintigraphy (P<0.05).
      The pooled DOR estimates for PET, MRI and bone scintigraphy were 365.5, 53.8 and
      34.4, respectively. The DOR for PET was significantly higher than for MRI and
      bone scintigraphy (P<0.05). There was no significant difference between MRI and
      bone scintigraphy (P>0.05). The SROC curve for PET showed better diagnostic
      accuracy than for MRI and bone scintigraphy. The SROC curve for MRI was better
      than for bone scintigraphy. The *Q index estimates for PET, MRI and bone
      scintigraphy were 0.933, 0.903 and 0.857, respectively. The *Q index for PET and
      MRI were significantly higher than for bone scintigraphy (P<0.05). There was no
      significant difference between PET and MRI (P>0.05). On a per-lesion basis, the
      pooled sensitivity estimates for PET, MRI and bone scintigraphy were 95.0, 83.8
      and 71.5%, respectively. The sensitivity for PET was significantly higher than
      for MRI and bone scintigraphy (P<0.05), and the sensitivity for MRI was
      significantly higher than for bone scintigraphy (P<0.05). The pooled specificity
      estimates for PET, MRI and bone scintigraphy were 94.6, 96.3 and 91.0%,
      respectively. The specificity for MRI was significantly higher than for PET and
      bone scintigraphy (P<0.05), and the specificity for PET was significantly higher
      than for bone scintigraphy (P<0.05). The pooled DOR estimates for PET, MRI and
      bone scintigraphy were 431.9, 158.1 and 9.0, respectively. The DOR for PET was
      significantly higher than for MRI and bone scintigraphy (P<0.05) and the DOR for
      MRI was significantly higher than for bone scintigraphy (P<0.05). The SROC curve
      for PET and MRI showed better diagnostic accuracy than for bone scintigraphy.
      There was no significant difference between PET and MRI. The *Q index estimates
      for PET, MRI and bone scintigraphy were 0.953, 0.962 and 0.778, respectively. The
      *Q index for PET and MRI were significantly higher than for bone scintigraphy
      (P<0.05). There was no significant difference between PET and MRI (P>0.05).
      CONCLUSION: (18)FDG PET was found to be the best modality to detect bone
      metastasis in patients with lung cancer, both on a per-patient basis and a per
      lesion basis; MRI had the highest specificity on a per-lesion basis. For the
      subgroup analysis of (18)FDG PET, PET/computed tomography was shown to be better
      than PET and there were no significant differences between using (68)Ge and
      computed tomography for attenuation correction on a per-patient basis.

PMID- 21094028
TI  - Selenium status and cardiometabolic health: state of the evidence.
AB  - Use of selenium enriched foods, supplements and fertilizers has increased
      markedly in recent years in the US and other Western countries because of the
      perception that the anti-oxidant properties of selenium could potentially reduce
      the risk of cancer and other chronic diseases. However, concern has been raised
      recently about possible adverse cardiometabolic effects of high selenium
      exposure, including an increased risk of diabetes and hyperlipidemia with high
      selenium intake. Hence, from a public health perspective, the relationship
      between selenium status and cardiometabolic health should be clarified in order
      to help guide consumers in their choices of nutritional supplements and enriched
      food products. Additional experimental evidence is needed to provide new insights
      into the role of selenium and of specific selenoproteins in human biology,
      especially to clarify the underlying mechanisms linking selenium to chronic
      disease endpoints. Further epidemiological studies and randomized clinical trials
      across populations with different selenium status should be conducted to
      determine the causal effect of selenium on cardiovascular disease and risk
      factors. Nevertheless, at the present time the widespread use of selenium
      supplements or other strategies that artificially increase selenium status above
      the level required for optimal selenoprotein activity is not justified and should
      not be encouraged.

PMID- 21094029
TI  - Heritability of body weight: moving beyond genetics.
AB  - Obesity is a complex disease, arising from the interaction between several
      genetic and environmental factors. Until recently, the genetic basis of complex
      diseases in general, and of obesity in particular, were poorly characterized.
      While the relatively rare monogenic and syndromic forms of obesity clearly
      recognize a genetic origin, the actual worldwide epidemics of obesity represent a
      challenge for the identification of the genetic factors involved, being likely
      the effect of several loci each having a subtle influence on the phenotypic
      expression. Progress in DNA analysis techniques and in computational tools, and
      the increasing level of characterization of the variability of the human genome
      has recently allowed to study comprehensively the association between genetic
      variants and obesity. To date, well-conducted and powered genome-wide association
      studies allowed to consistently identify genomic regions - lying on different
      chromosomes and affecting different metabolic pathways - influencing the
      predisposition to the accumulation of body fat, ultimately leading to overweight
      and obesity. However, the population attributable risk for obesity linked to the
      most statistically significant loci, like FTO and MC4R, remains discouragingly
      low, explaining only small fractions of the overall variance of body weight. In
      the last few years, the role of the complex interaction between genetic
      determinants and environmental factors in the rapid global increase of obesity
      has been further challenged by the entry of new players, that is the
      transcriptional and post-transcriptional regulation, summarized under the
      emerging discipline of epigenetics. The key challenge now is to move from the
      identification of causal genes and variants to the integration of different
      "omics" disciplines, finally allowing the molecular understanding of obesity and
      related conditions.

PMID- 21094030
TI  - Radix/rhizoma notoginseng extract (sanchitongtshu) for ischemic stroke: a
      randomized controlled study.
AB  - Agents of sanchi have been widely used as a complementary medicine for stroke in
      China. Sanchitongshu is a new Chinese patent medicine extracted from sanchi which
      has stronger anti-platelet activity than other agents of sanchi. Our aim was to
      investigate the synergistic action of low dose of aspirin combined with
      sanchitongshu capsule in the treatment of patients with light and moderate
      ischemic stroke in acute and subacute stages. This was a multi-center, double
      blinded, randomized controlled clinical trial conducted in four hospitals in
      China from July 2004 to 2006. 140 patients of ischemic stroke in anterior
      cerebral circulation within 30 days of onset were enrolled. Participants were
      assigned either to receive aspirin (50mg per day) and sanchitongshu capsule
      (200mg three times a day) or aspirin (50mg per day) and placebo capsule. Low dose
      of aspirin combined with sanchitongshu capsule significantly ameliorated
      neurological deficit (increased score of ESS: t=-5.02, p<0.0001) and activities
      of daily living (increased score of BI: t=-2.4, p=0.0178) after treatment
      compared with aspirin alone. Adverse reaction which occurred equally in both
      arms, was light to moderate and disappeared without special treatment.
      Sanchitongshu capsule, as a complementary medicine to aspirin, was effective in
      improving outcomes after ischemic stroke. It was a safe drug in our trial.

PMID- 21094031
TI  - Regulation of innate immunity by signaling pathways emerging from the endoplasmic
      reticulum.
AB  - The innate immune system has evolved the capacity to detect specific pathogens
      and to interrogate cell and tissue integrity in order to mount an appropriate
      immune response. Loss of homeostasis in the endoplasmic reticulum (ER) triggers
      the ER-stress response, a hallmark of many inflammatory and infectious diseases.
      The IRE1/XBP1 branch of the ER-stress signaling pathway has been recently shown
      to regulate and be regulated by innate immune signaling pathways in both the
      presence and absence of ER-stress. By contrast, innate immune pathways negatively
      affect the activation of two other branches of the ER-stress response as
      evidenced by reduced expression of the pro-apoptotic transcription factor CHOP.
      Here we will discuss how innate immune pathways and ER-signaling intersect to
      regulate the intensity and duration of innate immune responses.

PMID- 21094032
TI  - The role of SLAM/CD2 polymorphisms in systemic autoimmunity.
AB  - The SLAM/CD2 gene family encodes receptors that play important roles in
      regulating multiple cellular interactions in the adaptive and innate immune
      systems. Three members of this gene family, Ly108, Ly9, and CD84, exhibit
      polymorphisms that strongly influence susceptibility to systemic autoimmunity,
      notably in mice, but also in some human populations. Polymorphisms of Ly108 in
      mice strongly impact central tolerance in both B and T cell development,
      predominantly by modulating apoptosis, anergy, and cell-cycle progression. In
      addition, Ly108 and CD84, together with their downstream signaling adaptor SLAM
      associated protein (SAP), have emerged as key players in B-T interactions during
      the formation of germinal centers. Interestingly, several independent lines of
      research have now associated variations in B-T interactions during germinal
      center formation with systemic autoimmunity, suggesting that susceptibility to
      systemic lupus erythematosus (SLE) may involve in part the impairment of this
      peripheral tolerance checkpoint. These new insights into the multiplicity of
      roles played by the SLAM/CD2 family and its potential importance in human
      autoimmunity positions the SLAM/CD2 family as an excellent target for
      immunotherapy.

PMID- 21094033
TI  - The lung permeability index: a feasible measurement of pulmonary capillary
      permeability.
AB  - BACKGROUND: We performed this study to determine the pulmonary capillary
      permeability (PCP) measuring radiolabeled human serum albumin leakage into the
      lung. The objective was to use PCP to differentiate between cardiogenic and non
      cardiogenic pulmonary edema etiologies. METHODS: We conducted this study in 10
      patients admitted to the intensive care unit who had recently developed bilateral
      pulmonary infiltrates and required hemodynamic monitoring. In these patients we
      determined the association among the lung permeability index, cardiac output,
      pulmonary capillary wedge pressure, myocardial performance index, and the protein
      content of the bronchoalveolar lavage as expressed by bronchoalveolar lavage
      (BAL) total protein and BAL-to-serum protein ratio. Twenty mCi of technetium
      labeled albumin was injected and measure in the heart and the lung at 10 and 180
      min post-injection. Lung and heart uptake ratios as well as the lung permeability
      index were calculated. RESULTS: We found a good correlation between the lung
      permeability index and both the myocardial performance index (cardiac
      output/pulmonary capillary wedge pressure) and the total protein content of the
      bronchoalveolar lavage fluid. CONCLUSION: The lung permeability index is a
      feasible, noninvasive estimation of the pulmonary capillary permeability.

PMID- 21094034
TI  - Participation of lectin chaperones and thiol oxidoreductases in protein folding
      within the endoplasmic reticulum.
AB  - Protein folding within the endoplasmic reticulum occurs in conjunction with a
      complex array of molecular chaperones and folding catalysts that assist the
      folding process as well as function in quality control processes to monitor the
      outcome. In this review, we summarize recent advances in the
      calnexin/calreticulin chaperone system that is directed primarily toward Asn
      linked glycoproteins, as well as the protein disulfide isomerase family of
      enzymes that catalyze disulfide formation, reduction, and isomerization. We
      highlight issues related to function and substrate specificity as well as the
      functional interplay between the two systems.

PMID- 21094036
TI  - Biodegradation and biotransformation of explosives.
AB  - Explosives now contaminate millions of hectares of land in the US alone, with
      global levels of contamination difficult to fully assess. Understanding the
      biology behind the metabolism of these toxic compounds by microorganisms and
      plants is imperative for managing these pollutants in the environment. Towards
      this aim, recent studies have identified, and are now characterizing, plant genes
      involved in 2,4,6-trinitrotoluene detoxification and the biochemical pathways of
      nitramine degradation in microorganisms. A key scientific goal continues to be
      identification of enzymes capable of degrading 2,4,6-trinitrotoluene and this
      still remains elusive, although recent reports give insights into the origin of
      nitrite released during biotransformation of this major contaminant. Promising
      phytoremediation research using transgenic model plant systems has now been
      transferred to poplar, a species with field applicability.

PMID- 21094035
TI  - Chaperone-mediated autophagy in protein quality control.
AB  - Chaperone-mediated autophagy is a selective mechanism for degradation of soluble
      cytosolic proteins in lysosomes that distinguishes itself from other autophagic
      pathways by the selectivity with which CMA substrates are targeted for
      degradation. The recent molecular dissection of this autophagic pathway and the
      development of experimental models with compromised CMA have unveiled the
      important contribution of this pathway to protein quality control. In fact, CMA
      activation seems to be a common mechanism of cellular defense against
      proteotoxicity.

PMID- 21094037
TI  - An analysis of research activity in major UK cancer centres.
AB  - The organisation of cancer research is critical to its overall creativity and
      productivity. Cancer centres are a major organisational structure for this
      research, however, little is known about their effect on research or how national
      policy-making intersects with this complex policy nexus. This study of the
      evolution of United Kingdom cancer centres (UKCC), part of a wider European and
      United States programme, uses a bibliometric analysis of research activity prior
      to the creation of the NCRI and after its formation (1995-2004/5). In terms of
      critical research mass UKCC are very heterogeneous with a fourfold difference
      between the top and bottom quintiles. UK centres published just over one eighth
      of the total UKCC in 1995 but almost a quarter by 2004. This centrification
      occurred in the absence of any national strategy. Overall these centres conduct
      more fundamental (laboratory-based) research than that being conducted in the
      wider network but this hides major heterogeneity. UKCC collaborate with European
      investigators in 5-28% of all their outputs and with USA the range is between 6%
      and 21%. We have also derived new measures of research impact on clinical
      management and the general public as well as the impact of national policy on
      research assessment for certain types of cancer research.

PMID- 21094039
TI  - The prognostic significant of percentage drop in serum CEA post curative
      resection for colon cancer.
AB  - OBJECTIVE/BACKGROUND: This study aimed to analyze the hypothesis that increased
      percentage drop in serum CEA post curative resection for colon cancer is
      associated with improved survival. METHODS: Five hundred thirty three patients
      who underwent colon resection with a curative intent were retrospectively
      analyzed for their pre- and postoperative CEA levels. The disease-free and
      overall survival curves were calculated using Kaplan Meier analysis to evaluate
      cancer related outcomes. For multivariate analysis, the Cox regression model was
      used. RESULTS: The estimated 5-year overall survival for the preoperative serum
      CEA > 5 ng/mL group with respect to a postoperative CEA level drop rate of 40%,
      50% and 60% were 72.9%, 80.9% and 81.8%, respectively. The estimated 5-year
      overall survival for the preoperative serum CEA <= 5 ng/mL group with respect to
      each postoperative CEA level drop rate were 86.6%, 97.1% and 97.7%, respectively
      (P = 0.257, P = 0.092 and P = 0.073, respectively). The prognostic factors for
      poor survival were the depth of invasion (p = 0.042, hazard ratio: 2.617, 95% CI
      = 1.021-3.012) and lymph node metastasis (p = 0.008, hazard ratio: 2.249, 95% CI
      = 1.231-4.111). A 60% drop of the CEA level was an independent prognostic factor
      for survival (p = 0.001, hazard ratio: 2.954, 95% CI = 1.686-5.176) for patients
      with a preoperative CEA level > 5 ng/mL. CONCLUSION: Determining the preoperative
      CEA level and the early postoperative percent drop of the serum CEA level may be
      a helpful factor for the prognosis of colon cancer patients. However, the percent
      drop from the pre to postoperative CEA level from the normal range was not
      associated with survival difference.

PMID- 21094038
TI  - Are patients in clinical trials representative of the general population? Dose
      intensity and toxicities associated with FE100C-D chemotherapy in a non-trial
      population of node positive breast cancer patients compared with PACS-01 trial
      group.
AB  - PURPOSE: In our institution, adjuvant taxanes are currently offered to fit, node
      positive breast cancer patients who are either Her2 positive (any ER/PR) or
      triple negative (ER/PR/Her2 negative). The FE(100)C-D (FE(100)C * 3->docetaxel
      100mg/m(2) * 3) regime, based on the PACS 01 trial [Roche H, Fumoleau P,
      Spielmann M, et al. Sequential Adjuvant Epirubicin-Based and Docetaxel
      Chemotherapy for node positive Breast Cancer Patients: The FNCLCC PACS 01 Trial.
      J Clin Oncol 2006;24:5664-5671] is used. We retrospectively audited our
      experience with FE(100)C-D at The Beatson West of Scotland Cancer Centre and one
      representative district general hospital (DGH), Falkirk and District Royal
      Infirmary (FDRI). PATIENTS AND METHODS: Over a two year period, 101 patients
      commenced adjuvant FE(100)C-D chemotherapy. Data was matched with the FE(100)C-D
      arm of the PACS 01 trial. RESULTS: Median age was 54 years. Twenty-six patients
      (26%) had >= 1 episode of febrile neutropaenia (FN), including one fatal episode.
      Twenty-nine percent of patients required treatment interruption >= 1 week. Thirty
      percent of patients had dose reductions. Thirty percent of patients received <90%
      dose intensity of docetaxel. CONCLUSION: The FN rate was substantially higher and
      docetaxel dose intensity substantially lower in our unselected sample of patients
      than in the reference study.(1) This 'real-life' data illustrates the problems of
      applying clinical trial data to the more generalised patient population.

PMID- 21094040
TI  - Application of calcined waste fish (Labeo rohita) scale as low-cost heterogeneous
      catalyst for biodiesel synthesis.
AB  - This paper explores the feasibility of converting waste Rohu fish (Labeo rohita)
      scale into a high-performance, reusable, low-cost heterogeneous catalyst for
      synthesis of biodiesel from soybean oil. The thermo-gravimetric analysis (TGA)
      and X-ray diffraction (XRD) analysis revealed that a significant portion of the
      main component of fish scale i.e. HAP (hydroxyapatite) could be transformed into
      beta-tri-calcium phosphate when calcined above 900 degrees C for 2 h. Scanning
      Electron Microscopy (SEM) morphology studies of the calcined scale depicted a
      fibrous layer of porous structure; while a BET surface area of 39 m(2)/g was
      measured. Response surface methodology (RSM) was employed to determine the
      optimal parametric conditions viz. methanol/oil molar ratio, 6.27:1, calcination
      temperature, 997.42 degrees C and catalyst concentration, 1.01 wt.% of oil
      corresponding to a maximum FAME yield of 97.73%. Reusability results confirmed
      that the prepared catalyst could be reemployed up to six times, procreating a
      potentially applicable avenue in biodiesel synthesis.

PMID- 21094041
TI  - Biodiesel production from rubber seed oil using poly (sodium acrylate) supporting
      NaOH as a water-resistant catalyst.
AB  - Poly (sodium acrylate) supporting NaOH (NaOH/NaPAA) was prepared by in situ
      polymerization of aqueous solution of acrylic acid with an over-neutralization by
      adding excess of NaOH. NaOH/NaPAA presented a promising selectivity for water
      absorbency and good water retention with negligible swelling capacity in the
      organic solvents of methanol, glycerol, rubber seed oil methyl esters, and rubber
      seed oil. NaOH/NaPAA catalysts showed a basic strength of 15.0<H_<18.4 and their
      basicity increased with the increase of the NaOH loading amount. NaOH/NaPAA
      catalysts exhibited almost the same catalytic activity in the transesterification
      of rubber seed oil with methanol under the optimized reaction conditions compared
      to conventional homogeneous NaOH catalyst. Furthermore, the functional
      absorbent/catalyst system presented a good water resistance in the
      transesterification which retained high catalytic activity when a water
      concentration in the reaction system was less than 2 wt.%.

PMID- 21094042
TI  - Simultaneous oxidation of ammonium, p-cresol and sulfide using a nitrifying
      sludge in a multipurpose bioreactor: a novel alternative.
AB  - A nitrifying continuous stirred tank reactor was used as multipurpose bioreactor
      and it was operated for 325 days at 220 mg NH(4)(+)-N/Ld, 89 mg p-cresol-C /Ld
      and 36-76 mg S(2-)/Ld. The bioreactor was fed in sequential way, firstly with
      ammonium, achieving a consumption efficiency of 89%, with a nitrate yield of
      0.99. Afterward, p-cresol was fed, achieving ammonium and p-cresol consumption
      efficiencies of 95% and 100%, respectively. The nitrate yield was higher and no
      aromatic intermediaries from p-cresol were detected. Finally sulfide was fed and
      the consumption efficiencies for all substrates were of 100%, being nitrate,
      HCO(3)(-) and sulfate the end products. The kinetic results showed that
      biological sulfide consumption was 13-fold faster than the chemical oxidation.
      This is the first time that a nitrifying reactor can be used for multiple
      purposes and also for the simultaneous removal of ammonium, sulfide and p-cresol
      in one step.

PMID- 21094043
TI  - Pressurised pyrolysis of Miscanthus using a fixed bed reactor.
AB  - Miscanthus x giganteus was pyrolysed, in a fixed bed reactor in a constant flow
      of dinitrogen gas, at a rate of 13 degrees C/min from ambient to 550 degrees C,
      then held for 25 min at this temperature. The pressures employed ranged from
      atmospheric to 26 bar. The major compounds identified in the bio-oil were water,
      phenol, and phenol derivatives. The water contents impact on the usefulness of
      the bio-oil as a fuel. However, the phenols could provide useful platform
      chemicals and products. The properties of the char were determined using
      elemental analyses, surface area measurements using the Brunauer-Emmett-Teller
      equation, a calorimetric bomb, Scanning Electron Microscopy, and solid state
      (13)C NMR spectroscopy. The chars were highly carbonised, especially at the
      higher pressures, and provided thermally stable materials. Pressure impacted
      greatly on the surface area. Char formed at atmospheric pressure had a surface
      area of 162 m(2)/g, whereas that from the highest pressure applied was only 0.137
      m(2)/g.

PMID- 21094044
TI  - Construction and characterization of a photosynthetic bacterium genetically
      engineered for Hg2+ uptake.
AB  - A recombinant photosynthetic bacterium, Rhodopseudomonas palustris, was
      constructed to simultaneously express mercury transport system and
      metallothionein for Hg(2+) removal from heavy metal wastewater. The effects of
      essential process parameters, including pH, ionic strength and presence of co
      ions on Hg(2+) uptake were evaluated. The results showed that compared with wild
      type R. palustris, recombinant strain displayed stronger resistance to toxic
      Hg(2+), and its Hg(2+) binding capacity was enhanced threefolds. In the range of
      pH 4-10, recombinant R. palustris maintained effective accumulation of Hg(2+).
      The presence of 10 mg L(-1) Mg(2+), Ca(2+), Zn(2+) or Ni(2+) did not
      significantly influence Hg(2+) bioaccumulation by recombinant R. palustris from
      solutions containing 0.2 mg L(-1) Hg(2+), while Na(+) and Cd(2+) posed serious
      adverse effect on Hg(2+) uptake. Furthermore, EDTA treatment experiment confirmed
      that different from wild type R. palustris that mainly absorbed Hg(2+) on the
      cell surface, recombinant R. palustris transported most of the bound Hg(2+) into
      the cells.

PMID- 21094045
TI  - Biodiesel production from Jatropha oil by catalytic and non-catalytic approaches:
      an overview.
AB  - Biodiesel (fatty acids alkyl esters) is a promising alternative fuel to replace
      petroleum-based diesel that is obtained from renewable sources such as vegetable
      oil, animal fat and waste cooking oil. Vegetable oils are more suitable source
      for biodiesel production compared to animal fats and waste cooking since they are
      renewable in nature. However, there is a concern that biodiesel production from
      vegetable oil would disturb the food market. Oil from Jatropha curcas is an
      acceptable choice for biodiesel production because it is non-edible and can be
      easily grown in a harsh environment. Moreover, alkyl esters of jatropha oil meet
      the standard of biodiesel in many countries. Thus, the present paper provides a
      review on the transesterification methods for biodiesel production using jatropha
      oil as feedstock.

PMID- 21094046
TI  - Discovery of a novel hybrid from finasteride and epristeride as 5alpha-reductase
      inhibitor.
AB  - Finasteride and epristeride both inhibit 5alpha-reductase with high potency via
      competitive and non-competitive mechanism, respectively. A new hybrid of
      finasteride and epristeride was designed as a new 5alpha-reductase inhibitor
      based on combination principles in medicinal chemistry. Human 5beta-reductase was
      chosen as a plausible surrogate of 5alpha-reductase type II and the results
      indicate that although the hybrid compound possesses the main bulk of
      epristeride, its inhibitory mechanism is same as of finasteride. The hybrid
      turned out to be a potent 5alpha-reductase inhibitor in low IC(50) ranges.

PMID- 21094047
TI  - 2-Arylbenzoxazoles as CETP inhibitors: raising HDL-C in cynoCETP transgenic mice.
AB  - We describe structure-activity studies leading to the discovery of 2
      arylbenzoxazole 3, the first in a series to raise serum high-density lipoprotein
      cholesterol levels in transgenic mice. Replacement of the 4-piperidinyloxy moiety
      with piperazinyl provided a more synthetically tractable lead, which upon
      optimization resulted in compound 4, an excellent inhibitor of cholesteryl ester
      transfer protein function with good pharmacokinetic properties and in vivo
      efficacy.

PMID- 21094048
TI  - The effects of skill focused instructions on walking performance depend on
      movement constraints in Parkinson's disease.
AB  - Previous research has shown that skill focused attention may be beneficial for
      the performance of complicated motor tasks in individuals with Parkinson's
      disease (PD). The objective of this study was to assess the impact of skill
      focused attention instructions on gait under temporal movement constraints that
      may reflect common challenges experienced in daily life. Eighteen patients with
      PD walked a straight pathway under two different attention focus conditions (no
      instruction, skill focused instruction) and two different walking speeds
      (preferred pace, as fast as possible). In the no instruction condition, patients
      were not told "where" attention should be directed. In the skill focused
      instruction condition, patients were told to focus on the foot contacting the
      floor with each step. Spatial and temporal gait measures, as well as, trunk sway
      were used to quantify walking performance. The results showed that when walking
      at a preferred pace, skill focused instructions benefited gait performance (e.g.,
      increased gait velocity, larger steps, more trunk sway). However, when walking as
      fast as possible, skill focused instructions had the opposite effect on gait
      performance (e.g., decreased gait velocity, smaller steps, and less trunk sway).
      This study demonstrates that skill focused instructions may contribute to the
      prioritization of stability under imposed temporal movement constraints.
      Clinicians should be aware of the processes involved in prioritization of
      movement components versus task goals in PD and the potential application of an
      attention based instructional set in altering priorities in this population.

PMID- 21094049
TI  - Cytotoxicity and topoisomerase I/II inhibition of glycosylated 2-phenyl-indoles,
      2-phenyl-benzo[b]thiophenes and 2-phenyl-benzo[b]furans.
AB  - A panel of glycosylated DNA binding agents (1-12) designed as functional
      anthracycline mimics was screened against three solid-tumor cell lines (MCF-7, HT
      29 and HepG2/C3A) and three non-tumor cell lines by the MTS (3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium) cell viability assay. Several compounds showed better in vitro
      cytotoxicity and selectivity against MCF-7 cells than daunomycin and doxorubicin,
      two known DNA binding agents that are clinically-used anti-cancer agents.
      Although the selectivity for HT 29 and HepG2/C3A cells is generally lower, the
      IC(50) values of some analogs against these two cancer cell lines were of the
      same magnitude as doxorubicin. Because there was no correlation between DNA
      binding affinity and cytotoxicity, and because topoisomerase (Topo) inhibition is
      another biological mechanism of action of most anthracycline drugs, Topo I/II
      inhibition assays with 1-12 were performed. Some of the compounds showed strong
      inhibition against these enzymes at 100MUM, but there was no clear correlation
      between cytotoxicity and Topo I/II inhibition ability. Topo I/II inhibition mode
      assays were also performed, which verified that these compounds are topoisomerase
      suppressors, not poisons. Based on these results, we conclude that although DNA
      binding and/or topoisomerase inhibition may contribute to the observed
      cytotoxicity of 1-12, other mechanisms of action are also likely to be important.

PMID- 21094050
TI  - Anatomical shape analysis of the mandible in Caucasian and Chinese for the
      production of preformed mandible reconstruction plates.
AB  - PURPOSE: The purpose of this study was to evaluate and analyze statistical shapes
      of the outer mandible contour of Caucasian and Chinese people, offering data for
      the production of preformed mandible reconstruction plates. METHODS: A CT
      database of 925 Caucasians (male: n=463, female: n=462) and 960 Chinese (male:
      n=469, female: n=491) including scans of unaffected mandibles were used and
      imported into the 3D modeling software Voxim (IVS-Solutions, Chemnitz, Germany).
      Anatomical landmarks (n=22 points for both sides) were set using the 3D view
      along the outer contour of the mandible at the area where reconstruction plates
      are commonly located. We used morphometric methods for statistical shape
      analysis. RESULTS: We found statistical relevant differences between populations
      including a distinct discrimination given by the landmarks at the mandible. After
      generating a metric model this shape information which separated the populations
      appeared to be of no clinical relevance. The metric size information given by
      ramus length however provided a profound base for the production of standard
      reconstruction plates. CONCLUSION: Clustering by ramus length into three sizes
      and calculating means of these size-clusters seem to be a good solution for
      constructing preformed reconstruction plates that will fit a vast majority.

PMID- 21094051
TI  - The Papworth Bleeding Risk Score: a stratification scheme for identifying cardiac
      surgery patients at risk of excessive early postoperative bleeding.
AB  - OBJECTIVE: We have developed a risk stratification score to identify cardiac
      surgical patients at higher risk of severe postoperative bleeding to aid a
      decision of whether to use a specific intervention preoperatively. METHODS: We
      prospectively created a database of 11592 consecutive patients, who underwent
      cardiac surgery with cardiopulmonary bypass. An adverse outcome was formally
      defined as a mean blood loss exceeding 2 ml kg(-1)h(-1) measured between arrival
      in the intensive care unit (ICU) and the earliest of the elapse of 3h; the start
      of transfusion of any one of fresh-frozen plasma, platelets or cryoprecipitate;
      return to theatre or death. Univariate and multivariate associations of severe
      postoperative bleeding with patient characteristics, clinical features and
      procedure details were analysed on a development set. The final risk
      stratification scheme was then evaluated on a test set. RESULTS: Severe
      postoperative bleeding was associated with urgent or emergency surgery, surgery
      that was not coronary artery bypass grafting or single valve surgery, presence of
      aortic valve disease, low body mass index and older age. A risk stratification
      score was constructed from the above variables to define preoperative categories
      that demonstrated high, medium and low risk of severe postoperative bleeding.
      Patients deemed to be at high, medium and low risk by our preoperative scoring
      had a 21% (95% confidence interval: 18-24%), 8% (7-10%) and 3% (2-4%) rate of
      severe postoperative bleeding, respectively, within the test set. CONCLUSION: We
      have developed a simple risk stratification score that can separate,
      preoperatively, patients into risk groups with markedly different rates of severe
      postoperative bleeding.

PMID- 21094052
TI  - Lessons from the comparison of two randomized clinical trials using gemcitabine
      and cisplatin for advanced biliary tract cancer.
AB  - There had been no standard chemotherapy established for advanced biliary tract
      cancer (BTC) until 2009, when the combination of cisplatin and gemcitabine (GC)
      was adopted as a first line standard chemotherapy option based on the results
      from two randomized studies: ABC-02, a UK investigator-initiated trial and the
      largest randomized phase III study in this tumor type with 410 patients; and
      BT22, a Japanese, industry-sponsored, randomized phase II study with 83 patients.
      In this review, investigators from both studies collaborated to compare
      protocols, patient characteristics, and outcomes of both studies including sub
      analyses of study results. Although both studies showed GC combination therapy to
      be more effective than monotherapy, a detailed comparison revealed disparities
      between efficacy and safety end-points between the studies, which did not
      necessarily arise from different populations but from differences in protocol
      design. This review provides clinicians with insights for advanced BTC clinical
      study design and interpretation of historical studies.

PMID- 21094053
TI  - The perioperative granulocyte/lymphocyte ratio is a clinically relevant marker of
      surgical stress in patients with colorectal cancer.
AB  - PURPOSE: This study was to assess the clinical relevance of the blood
      granulocytes to lymphocytes (G/L) ratio as an early marker of surgical stress in
      patients with colorectal cancer. METHODS: Thirty-three patients with colorectal
      cancer were prospectively to undergo laparoscopic-assisted (n=12) or open (n=21)
      surgical resection. Granulocyte and lymphocyte counts were used to calculate the
      G/L ratios in blood samples from all patients before the operation and post
      operatively on days 1, 3 and 7. Additionally, serum inflammatory cytokines,
      interleukin (IL)-1beta, IL-6, IL-8, tumour necrosis factor (TNF)-alpha,
      granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF were assayed
      as markers of surgical stress. RESULTS: Seven of 33 patients developed unexpected
      complications. Serum IL-6 (P<0.0001), G-CSF (P=0.0257), and M-CSF (P<0.0001) were
      higher on day 1 vs before the operation. Similarly, the G/L ratios were higher on
      days 1-3 vs before the operation (P<0.0001) and then gradually decreased together
      with the surgical stress levels. The G/L ratios and the numbers of granulocytes
      and lymphocytes in the blood showed no correlation with serum IL-1beta or TNF
      alpha. In contrast, the G/L ratios and the numbers of granulocytes in the blood
      showed significant correlation with IL-6 (Rs=0.710, P<0.0001, Rs=0.653, P<0.0001,
      respectively), with G-CSF (Rs=0.626, P<0.0001, Rs=0.578, P<0.0001), with M-CSF
      (Rs=0.470, P<0.0001, Rs=0.372, P<0.0001). However, the number of lymphocytes
      showed inverse correlation with IL-6 (Rs=-0.493, P<0.0001), G-CSF (Rs=-0.440,
      P<0.0001) and M-SCF (Rs=-0.443, P<0.0001). CONCLUSION: The G/L ratio appears to
      be a simple and clinically relevant parameter for the assessment of perioperative
      stress in patients undergoing colorectal surgery.

PMID- 21094054
TI  - Fatigue-related decrease in Piper rhythm frequency of the abductor pollicis
      brevis muscle during isometric contractions.
AB  - The purpose of this study was to analyze how the frequency of the Piper rhythm of
      the abductor pollicis brevis muscle (APB) and thus of the rhythmic
      synchronization of motor units changes with fatigue. Fourteen subjects
      participated in the study. The EMG signals were measured during maximum voluntary
      contractions, and a mimicked motor unit action potential was used to simulate an
      EMG signal containing no rhythmicity. The simulated EMG was used as a reference.
      The Piper rhythm was extracted from the high frequency power (170-271 Hz) of the
      wavelet transformed real and simulated EMG data using the difference of the
      autocorrelation functions of the power. The study shows that the Piper rhythm of
      the APB muscle, its pacing frequency and pacing amplitude can be extracted from
      the EMG signal recorded during a fatiguing task. One can conclude that the pacing
      frequencies observed in various hands covered the whole frequency range of the
      Piper band which includes the beta and the gamma band frequencies observed in
      brain activity (17-60 Hz). While the pacing frequency decreased with fatigue the
      pacing amplitude did not change significantly. The Piper rhythm is a result of a
      changing central drive and its measurement thus allows observing changes of
      central drive to the muscle. The ability to better resolve the Piper rhythm in
      the EMG without using the coherence with the brain activity opens the possibility
      to study the behavior of central control in the peripheral signal.

PMID- 21094055
TI  - Benefits of prestroke use of angiotensin type 1 receptor blockers on ischemic
      stroke severity.
AB  - BACKGROUND: There is a general agreement that the stroke prevention benefit of
      antihypertensive agents is mainly based on their blood pressure lowering
      properties. The aim of this retrospective study was to assess the benefits of
      angiotensin type 1 receptor blockers (ARBs) used before the onset of ischemic
      stroke. METHODS: Data were obtained between April 2007 and March 2009 using the
      discharge statistics of the neurologic service at Juntendo hospital. We retrieved
      the demographic and clinical characteristics of stroke patients and functional
      status upon discharge assessed by the modified Rankin Scale (mRS) and Barthel
      index (BI). RESULTS: We enrolled 151 patients. Patients treated with ARBs were
      less often treated with a calcium channel blocker (CaB)/angiotensin-converting
      enzyme inhibitor (ACEI). They often had diabetes and showed better outcomes than
      the non-ARB group. Logistic regression analysis indicated that in patients with a
      mRS score of 0 to 2, older age (P < .007) was associated with severe outcomes,
      while the factor of pretreatment with ARB (P < .014) was associated with better
      outcomes. For patients with BI scores of more than 75, older age (P < .015) and
      large artery atherosclerosis (P < .035) were associated with severe outcomes.
      Logistic regression analysis identified the factor of pretreatment with ARB (P <
      .020) to be associated with better outcomes. CONCLUSIONS: ARB is widely used in
      patients with hypertension and cardiovascular disease, and our results further
      support this indication.

PMID- 21094056
TI  - Peri-operative novel 2009 H1N1 influenza virus infection successfully treated
      with oseltamivir and zanamivir in a lung transplant recipient.

PMID- 21094057
TI  - Association between renal function and CYP3A5 genotype in heart transplant
      recipients treated with calcineurin inhibitors.
AB  - BACKGROUND: The renal expression of the cytochrome P450 3A5 (CYP3A5) isoenzyme
      and of the adenosine triphosphate (ATP)-binding cassette (ABC) efflux transporter
      P-glycoprotein is inversely associated with calcineurin-induced nephrotoxicity.
      The aim of this study was to evaluate the association between polymorphisms of
      the genes encoding these proteins and the long-term renal function of heart
      transplant recipients treated with calcineurin inhibitors. METHODS: We performed
      a retrospective cohort study of 160 heart transplant recipients from two
      institutions who were discharged alive after transplant and who received a
      calcineurin inhibitor during follow-up. The aim of this study was to evaluate the
      impact of common variants of the genes encoding this isoenzyme (CYP3A5*1 and *3)
      and the transporter (ABCB1 G2677T/A and C3435T) on the renal function of these
      patients after heart transplantation. The primary end-point of the study was
      changes in the estimated glomerular filtration rate (eGFR) at hospital discharge;
      at 3, 6, 12, 18 and 24 months after heart transplant; and then every year for up
      to 9 years. RESULTS: After adjusting for independent predictors of eGFR during
      follow-up, CYP3A5 was significantly associated with eGFR after transplantation (p
      = 0.0002), with carriers of the CYP3A5*1 allele exhibiting a higher eGFR. None of
      the ABCB1 variants or haplotypes were associated with eGFR after transplantation.
      CONCLUSION: The CYP3A5*1 genetic polymorphism is a promising marker to identify
      heart transplant recipients least likely to develop renal dysfunction during long
      term treatment with a calcineurin inhibitor.

PMID- 21094058
TI  - Dietary therapies--an old idea with a new lease of life.
AB  - The ketogenic diet has been used for the treatment of epilepsy in childhood for
      almost 100 years. Although initial use was wide, the advent of antiepileptic
      drugs led to reduced utilisation. However, an apparently 'forgotten treatment'
      gained further popularity in the early 1990s when significant individuals gained
      benefit. This aside, although there are many open label trials to suggest benefit
      can be gained in children with drug resistant epilepsy it is only recently that
      definitive evidence from randomised controlled trials has become available. There
      continues to be a constant struggle with the demand for the resources required,
      and therefore availability and apparent management choice is limited.

PMID- 21094059
TI  - Screening of asymptomatic children for tuberculosis is a lateral chest radiograph
      routinely indicated?
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to determine whether a
      lateral chest radiograph provides additional diagnostic information to a
      posteroanterior (PA) radiograph in the screening of asymptomatic children with
      positive purified protein derivative (PPD) skin tests in a nonendemic area.
      MATERIALS AND METHODS: This was an Institutional Review Board-approved, Health
      Insurance Portability and Accountability Act-compliant, retrospective study of
      605 consecutive pediatric patients (294 males, 311 females; mean age, 10.8 +/-
      5.2 years) with positive PPD skin test results, who underwent PA and lateral
      chest radiographs between July 2003 and May 2009 at a tertiary care pediatric
      hospital in a nonendemic area for tuberculosis (TB). Two pediatric radiologists
      independently reviewed each chest radiograph for evidence of abnormalities that
      may be indicative of acute or chronic TB infection. The reviewers first analyzed
      the PA radiograph alone and subsequently evaluated the PA and the lateral
      radiograph together to determine whether any observed abnormality was identified
      only on the lateral radiograph. When an abnormality was detected on both PA and
      lateral radiographs, the reviewers determined whether the abnormality on the
      lateral radiograph changed the reviewer's decision based on the PA radiograph
      alone. Assessment of nonconcordance between PA and lateral chest radiographs for
      each reviewer was evaluated by the McNemar test of matched binary pairs.
      Agreement between reviewers for detecting abnormalities on radiographs was
      evaluated by using the kappa (kappa) statistic. RESULTS: The frequency of an
      abnormal chest radiograph related to TB was 1.8% (11/605). The PA radiograph
      showed abnormalities in all 11 (100%) children with radiographic abnormalities.
      Lateral radiographs showed abnormalities related to TB in 2 (18.2%) of 11 cases
      found to be abnormal on PA radiographs. Nine (81.8%) of 11 abnormalities on PA
      radiographs were not detected on the lateral chest radiographs. There was
      statistical evidence of nonconcordance between PA and lateral chest radiographs
      in detecting TB-related abnormalities for reviewer 1 (P < .001) and reviewer 2 (P
      = .004). In cases with abnormalities observed on both PA and lateral radiographs,
      there were no cases in which information obtained from the lateral chest
      radiograph resulted in a change in interpretation based on the PA radiograph
      alone. A high level of agreement was observed between the two independent
      reviewers in detecting TB-related abnormalities on PA radiographs (kappa = 0.84,
      P < .001). CONCLUSIONS: A PA radiograph alone is sufficient for TB screening of
      asymptomatic pediatric patients with positive PPD skin test results in an area
      non-endemic for TB.

PMID- 21094060
TI  - The fine line between pressure and pain: ask the horse.

PMID- 21094061
TI  - Prevalence and shedding patterns of Campylobacter spp. in longitudinal studies of
      kennelled dogs.
AB  - Dog ownership is considered a risk factor for campylobacteriosis in humans. This
      study investigated the prevalence and shedding of Campylobacter spp. in kennelled
      dogs. Faecal samples (n=399) were collected in longitudinal studies from 52 dogs
      in two kennels. Campylobacter spp. were isolated using charcoal-based selective
      agars and direct PCR. The prevalence of Campylobacter spp. in dogs in boarding
      kennels ranged from 46% (95% CI 22, 72) on entry, to 50% (95% CI 30, 70) overall,
      and in dogs in 'rescue' kennels from 68% (95% CI 49, 84) on entry to 73% (95%, CI
      56, 87) overall. C. upsaliensis was isolated from 62% (95% CI 48, 73) of the
      dogs, whilst C. jejuni was isolated from 15% (95% CI 7, 26) of animals. The
      majority of infected dogs entered the kennels already carrying Campylobacter
      spp., and remained infected throughout their stay. However, in some cases,
      shedding appeared to commence after kennelling. Given that the prevalence of C.
      upsaliensis and C. jejuni was relatively high in dogs from both boarding and
      rescue kennels, such animals may pose a zoonotic risk.

PMID- 21094062
TI  - Levetiracetam: safety and efficacy in neonatal seizures.
AB  - PURPOSE: Neonatal seizures are common, especially in prematurity. Phenobarbital
      (PB) currently represents the antiepileptic drug (AED) of choice, despite being
      related to increased neuronal apoptosis in animal models and cognitive impairment
      in human subjects. Levetiracetam (LEV) may have a more favorable profile since it
      does not cause neuronal apoptosis in infant rodents. METHODS: In a prospective
      feasibility study, LEV was applied as first-line treatment in 38 newborns with
      EEG-confirmed seizures, after ruling out hypoglycemia, hypocalcaemia,
      hypomagnesaemia and pyridoxin dependency. Initial intravenous doses of 10 mg/kg
      LEV were gradually increased to 30 mg/kg over 3 days with a further titration to
      45-60 mg/kg at the end of the week. Acute intervention with up to 2 intravenous
      doses of PB 20 mg/kg was tolerated during LEV titration. LEV was switched to oral
      as soon as the infants' condition allowed. Based on clinical observation, EEG
      tracings (aEEG/routine EEGs), and lab data, drug safety and anticonvulsant
      efficacy were assessed over 12 months. RESULTS: In 19 newborns a single PB dose
      of 20 mg/kg was administered, while 3 newborns received 2 PB doses. 30 infants
      were seizure free under LEV at the end of the first week and 27 remained seizure
      free at four weeks, while EEGs markedly improved in 24 patients at 4 weeks. In 19
      cases, LEV was discontinued after 2-4 weeks, while 7 infants received LEV up to 3
      months. No severe adverse effects were observed. CONCLUSIONS: These results
      illustrate the safety of LEV treatment in neonatal seizures, including
      prematurity and suggest LEV anticonvulsant efficacy. Additional PB treatment
      admittedly constitutes a methodological shortcoming due to the prolonged
      anticonvulsive efficacy of PB. Double blind prospective controlled studies and
      long-term evaluation of cognitive outcome are called for.

PMID- 21094063
TI  - Homonuclear mixing sequences for perdeuterated proteins.
AB  - We tested the performance of several (13)C homonuclear mixing sequences on
      perdeuterated microcrystalline ubiquitin. All sequences were applied without (1)H
      decoupling and at relatively low MAS frequencies. We found that RFDR gave the
      highest overall transfer efficiency and that DREAM performs surprisingly well
      under these conditions being twice as efficient in the aliphatic region of the
      spectrum than the other mixing sequences tested.

PMID- 21094064
TI  - Oral reading after treatment of dense congenital unilateral cataract.

PMID- 21094066
TI  - Acquired myelinated nerve fibers in association with optic disk drusen.
AB  - Myelinated retinal nerve fibers are a well-recognized anomaly of the ocular
      fundus associated with many ocular and systemic conditions. Myelination is almost
      always congenital and stable, but progression has been documented in rare cases.
      Optic disk drusen are the result of a degenerative process at the optic nerve
      head and are often found incidentally on ophthalmologic examination. To our
      knowledge, optic disk drusen have only been reported once in association with
      acquired and progressive myelinated retinal nerve fibers. We present 2 such cases
      and consider the implications for the pathogenesis of myelinated nerve fibers.

PMID- 21094067
TI  - Comparison of botulinum toxin with surgery as primary treatment for infantile
      esotropia.

PMID- 21094068
TI  - Long-term results of vertical rectus muscle transposition and botulinum toxin for
      sixth nerve palsy.
AB  - PURPOSE: To report the long-term outcome of full-tendon vertical rectus muscle
      transposition combined with chemodenervation of the ipsilateral medial rectus
      muscle for acquired chronic sixth (abducens) nerve palsy. METHODS: A
      retrospective study of all patients treated for severe abduction deficit with
      transposition plus botulinum toxin over the course of 11 years. Minimum follow-up
      was 12 months. Main outcome measures were the surgical result and its stability.
      RESULTS: A total of 22 patients were included. Mean age at the time of surgery
      was 41.7 +/- 19.1 years (range, 4.5-69). The etiologies for the palsy were head
      trauma (11), tumor (10), and idiopathic (1). Mean follow-up time was 44.2 +/-
      37.4 months (range, 12-123). The average distance deviation was 38.1(Delta) +/-
      11.6(Delta) preoperatively, 4.0(Delta) +/- 16.1(Delta) 3 months after the
      operation (p = 0.0004), and 7.9(Delta) +/- 8.8(Delta) at 12 months (p = 0.0003),
      with no subsequent change. At the final examination, on average 44.2 months after
      the operation, 13 patients (59%) were within 10(Delta) of alignment, 2 (1%) were
      overcorrected, and 7 (32%) had vertical deviations. The majority of patients
      (73%) had no double vision in the primary position. No patient developed anterior
      segment ischemia. CONCLUSIONS: Vertical rectus muscle transposition combined with
      intraoperative botulinum toxin injection into the ipsilateral medial rectus
      muscle improved alignment in patients with complete chronic sixth nerve palsy.
      While the effects of treatment may have diminished slightly during the first year
      after surgery, they remained stable thereafter.

PMID- 21094069
TI  - Binding research on flavones as ligands of beta-amyloid aggregates by
      fluorescence and their 3D-QSAR, docking studies.
AB  - The K(d)s (dissociation constants) of 21 flavone derivatives have been obtained
      by fluorescence in vitro when binding with Abeta(1-40) (beta-amyloid(1-40))
      aggregates protein. Extensive 3D-QSAR (quantitative structure-activity
      relationship) studies were performed on the fluorescent flavones, which are
      excellent ligands of Abeta(1-40) aggregates protein. Comparative molecular
      similarity indices analysis (CoMSIA) technique was used to relate the binding
      affinities with the ligand structures, and the QSAR model was obtained using the
      CoMFA technique. The QSAR model was proved to statistically significant and have
      high predictive power: the CoMSIA model yielded the cross-validated q2 = 0.512
      and the non-cross-validated r2 = 0.911. This model showed that electrostatic
      (22.5%) and H-bond interaction (acceptor 15.3%; donor 45.1%) properties played
      major roles in ligand binding process. The QSAR model was further graphically
      interpreted in terms of field contribution maps. In order to further investigate
      the specific binding site of the flavones in the Abeta(1-40) aggregates,
      preliminary docking studies were performed. According to the 3D-QSAR results, the
      possible binding site in the protein was proposed in order to direct the
      molecular docking studies. A good correlation (R2: 0.846) between the calculated
      binding energies and the experimental binding affinities (pK(d)s) suggests that
      the identified binding site is reliable. The 3D-QSAR model and the information of
      the ligand-protein interaction will be helpful in the selection of flavones to be
      structurally modified and labeled by a radio nuclide for imaging Abeta(1-40)
      aggregates in the AD (Alzheimer's disease) brain.

PMID- 21094070
TI  - Structure and biological importance of the Spn1-Spt6 interaction, and its
      regulatory role in nucleosome binding.
AB  - Eukaryotic transcription and mRNA processing depend upon the coordinated
      interactions of many proteins, including Spn1 and Spt6, which are conserved
      across eukaryotes, are essential for viability, and associate with each other in
      some of their biologically important contexts. Here we report crystal structures
      of the Spn1 core alone and in complex with the binding determinant of Spt6.
      Mutating interface residues greatly diminishes binding in vitro and causes strong
      phenotypes in vivo, including a defect in maintaining repressive chromatin.
      Overexpression of Spn1 partially suppresses the defects caused by an spt6
      mutation affecting the Spn1 interface, indicating that the Spn1-Spt6 interaction
      is important for managing chromatin. Spt6 binds nucleosomes directly in vitro,
      and this interaction is blocked by Spn1, providing further mechanistic insight
      into the function of the interaction. These data thereby reveal the structural
      and biochemical bases of molecular interactions that function in the maintenance
      of chromatin structure.

PMID- 21094071
TI  - Cryptococcal immune reconstitution syndrome during steroid withdrawal treated
      with hydroxychloroquine.
AB  - We present a case report of cryptococcal immune reconstitution syndrome (IRS), in
      a non HIV infected patient, which we treated with hydroxychloroquine with
      successful results. We briefly review cryptococcal IRS, possible mechanisms of
      action of hydroxychloroquine as an immunomodulatory agent, and its potential role
      in management of IRS.

PMID- 21094072
TI  - A novel 60 kDa reactivity in cyclic neutropenia: high titer cytoplasmic ANCA
      immunostaining pattern and negative anti-proteinase-3 antibody.

PMID- 21094073
TI  - Primary lung adenocarcinoma associated with anti-Jo-1 positive polymyositis.
AB  - We present a female with anti-Jo-1 positive polymyositis and lung adenocarcinoma.
      Her polymyositis diagnosis was based on her clinical symptoms, electromyography
      results, and highly elevated muscle enzymes, including creatine kinase and
      lactate-dehydrogenase. Anti-Jo-1 positivity, leukocytosis and elevated tumor
      markers: CA 15-3 and CA 72-4 were also certified at the diagnosis. Her malignancy
      was finally diagnosed by transthoracic needle biopsy, two years after the
      appearance of first symptoms of polymyositis. After surgical removal of the
      tumor, polymyositis was in remission. Due to the symptoms mentioned above and the
      coincidence of the tumor, a paraneoplastic myositis was suspected.

PMID- 21094074
TI  - The restorative benefits of walking in urban and rural settings in adults with
      good and poor mental health.
AB  - People differ in their potential for psychological restoration but there is
      little evidence on the role of varying mental health state or settings in the
      process. This paper reports two quasi-experiments which compare the restorative
      benefits of walking in urban and rural settings in two groups of adults with good
      and poor mental health. Two aspects of restoration are examined, firstly mood,
      the other using personal project techniques (Little, 1983) to capture an under
      explored aspect of cognitive restoration through reflection on everyday life
      tasks. Results are consistent with a restorative effect of landscape: the rural
      walk was advantageous to affective and cognitive restoration in both health
      groups when compared to an urban walk. However, beneficial change took place to a
      greater extent in the poor health group. Differential outcomes between health
      groups were found in the urban setting, which was most advantageous to
      restoration in the poor mental health group. This study extends restorative
      environments research by showing that the amount of change and context for
      restoration can differ amongst adults with variable mental health.

PMID- 21094075
TI  - Neck/shoulder pain is more strongly related to depressed mood in adolescent girls
      than in boys.
AB  - A cross-sectional study of 1258, 14 year old girls and boys used self-report and
      physical examination measures to assess neck/shoulder pain in the last month,
      depressed mood, physical fitness, body composition, self-efficacy, global self
      worth, family functioning and social advantage. The data was used to compare the
      relationship between depressed mood and neck/shoulder pain (NSP) in adolescent
      girls and boys. The prevalence of NSP in girls (34%, 211/621) was significantly
      greater than in boys (21%, 134/637; p < .001). After controlling for covariates,
      girls with medium (OR = 4.28; CI = 2.31-7.92; p < .001) and high depressed mood
      (OR = 8.63; CI = 4.39-16.98; p < .001) were significantly more likely to report
      NSP than girls with low depressed mood. Depressed mood was also a significant
      correlate of NSP in boys after controlling for covariates, although the
      association was substantially weaker (OR = 2.44; CI = 1.29-4.61; p < .001). After
      controlling for relevant biological, psychological and social covariates,
      depressed mood was a significant correlate of NSP in both sexes; but the
      association between depressed mood and NSP was significantly stronger for girls
      than for boys.

PMID- 21094076
TI  - Transcription strength and halophytic lifestyle.

PMID- 21094077
TI  - Case report: Chalazion and its features visualized by ultrahigh resolution
      optical coherence tomography.
AB  - PURPOSE: The purpose of this case report is to highlight the clinical
      characteristics of a recurrent chalazion through the use of digital photography
      and ultra-high resolution optical coherence tomography (UHROCT). CASE REPORT: A
      single case is presented, along with digital biomicroscopic photographs and
      UHROCT images. DISCUSSION: A review of the literature describing the
      histopathological and associations of chalazia and other disorders, suggest it
      may be possible to differentiate different eyelid conditions based on their
      clinical manifestations and appearance on UHROCT tomograms. Based on the images
      presented here, it appears that this case is typical of a post-menopausal
      incidence of chalazion and risk for acne rosacea.

PMID- 21094078
TI  - Developmental control of endocycles and cell growth in plants.
AB  - Timely progression of the mitotic cell cycle is central for growth and
      development of plant organs. Many cell types in plants also enter an alternative
      cell cycle called the endoreduplication cycle or endocycle in which cells
      increase their ploidy through repeated rounds of chromosomal replication without
      cell divisions. The transition from the mitotic cycle into the endocycle often
      coincides with the initiation of cell expansion and cell differentiation, and
      strong correlations between final ploidy level and cell size have been reported
      in many plant species. Recent studies have begun to unveil how developmental
      signals modulate entry and exit of the endocycle through both transcriptional and
      post-transcriptional mechanisms. An increase in ploidy by endocycles is not an
      ultimate determinant of plant cell size and it is likely that it sets the maximum
      capacity for future cellular growth.

PMID- 21094079
TI  - Complexation of nitrogen and sulphur donor Schiff's base ligand to Cr(III) and
      Ni(II) metal ions: synthesis, spectroscopic and antipathogenic studies.
AB  - 2,6-diacetyl pyridine based ligand was synthesized by the reaction of 2,6
      diacetyl pyridine with thiocarbohydrazide in presence of acetic acid. The
      coordination compounds with Cr(III) and Ni(II) metal ions having [Cr(L)X]X2 and
      [Ni(L)X]X compositions (where L=ligand and X=NO3-, Cl- and CH3COO-) were
      synthesized and characterized by physicochemical and spectral studies. The
      studies like elemental analyses, molar conductance measurements, magnetic
      susceptibility measurements, IR, UV-Vis, NMR, mass and EPR reveal that the
      complexes are octahedral. The compounds were examined against the pathogenic
      fungal and bacterial strains like Alternaria brassicae, Aspergillus niger,
      Fusarium oxysporum, Xanthomonas compestris and Pseudomonas aeruginosa. A. niger
      causes the diseases Apergillosis and Otomycosis in humans.

PMID- 21094080
TI  - Investigation of causes of oseltamivir chemoprophylaxis failures during influenza
      A (H1N1-2009) outbreaks.
AB  - BACKGROUND: Antiviral post-exposure prophylaxis with oseltamivir has been used as
      a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been
      few reports of well-documented prophylaxis failures and the reasons for failure.
      OBJECTIVES: We report herein a series of 10 cases of prophylaxis failures and
      explore the reasons behind their prophylaxis failure. STUDY DESIGN: In the early
      pandemic phase, the military employed oseltamivir post-exposure ring-prophylaxis
      of affected units. From June 22 to July 30, 2009, cases of laboratory-confirmed
      prophylaxis failures were identified. Nasopharyngeal swabs were collected and
      tested by PCR. Samples with sufficient RNA material were sent for whole genome
      sequencing, and screened for mutations that confer oseltamivir resistance,
      especially the H275Y mutation. RESULTS: Ten cases of laboratory-confirmed
      prophylaxis failure were identified, with a mean age of 22.3 years. One case was
      asymptomatic; the remaining 9 had fever or cough but without severe
      complications. The mean duration of exposure before starting oseltamivir was 1.9
      days (SD 0.9), while the mean duration of oseltamivir consumption before symptom
      onset was 1.9 days (SD 1.4). None of the samples had the H275Y mutation or other
      known mutations that confer resistance. From the whole genome sequencing, several
      mutations at the HA (T220S, E275V, T333A, D239G); PB2 (K660R, L607V, V292I); NS1
      (F103S), and NP (W104G) gene segments were detected, but none of them were likely
      to result in anti-viral resistance. CONCLUSIONS: Primary prophylaxis failures
      exhibited mild symptoms without complications; all did not have the H275Y
      mutation and were unlikely to result from other mutations.

PMID- 21094081
TI  - Eradication of disseminated adenovirus infection in a pediatric hematopoietic
      stem cell transplantation recipient using the novel antiviral agent CMX001.
AB  - Adenovirus infection is a serious and often fatal complication in hematopoietic
      stem cell transplant patients. There are currently no FDA-approved therapies for
      adenovirus infection, with only anecdotal, off-label uses described for a variety
      of anti-viral agents or immune therapies. We report the first case of successful
      eradication of disseminated adenovirus infection by the novel antiviral agent
      CMX001 in a severely immunocompromised pediatric stem cell transplant recipient
      following failure to respond to intravenous cidofovir. Complete clinical and
      virologic response was documented; virologic and pharmacokinetic data are
      reported. CMX001 is a promising new oral antiviral agent under development for
      the prophylaxis and treatment of severe infections caused by double-stranded DNA
      viruses including adenovirus in immunocompromised patients.

PMID- 21094083
TI  - Rolandic spikes--the challenge to differentiate between benign and malignant
      pediatric epilepsies.

PMID- 21094082
TI  - Serological evidence of Merkel cell polyomavirus primary infections in childhood.
AB  - BACKGROUND: Merkel cell polyomavirus (MCPyV) was identified newly (2008) and is
      believed to be an etiologic factor of Merkel cell carcinoma (MCC). Recent
      molecular and serological data suggest that MCPyV infection is common in the
      general population. OBJECTIVES: The aim of this study was to investigate the age
      of primary exposure to MCPyV. STUDY DESIGN: A MCPyV-IgG EIA was developed using
      the MCPyV major capsid protein VP1 expressed and self-assembled into virus-like
      particles (VLPs) in insect cells. The assay was used to detect serum IgG
      antibodies in two groups of children. Group 1 comprised paired and 5-8 year
      follow-up sera from 217 children (3-13 years) with acute lower respiratory tract
      infection. Group 2 comprised sera from 158 children (1-4 years) with otitis
      media; 86 children underwent adenoidectomy and 72 did not, whereafter follow-up
      sera were obtained 3 years later. RESULT: The prevalence of MCPyV-IgG was 9% at 1
      4 years, and increased to 35% at 4-13 years among subjects from Group 1, with a
      33% seroconversion rate during 5-8 years. Among Group 2, the seroconversion rate
      was 16% during 3 years. The IgG prevalence at 4-7 years as well as the IgG levels
      showed an apparent gender difference, with male preponderance prevailing among
      the children without adenoidectomy. CONCLUSION: MCPyV primary infections occur
      ubiquitously in childhood, and the first exposure takes place at young age. The
      serology showed no evidence for a causative role of MCPyV in lower respiratory
      tract infection manifesting as acute wheezing, but was compatible with the notion
      of MCPyV persistence in tonsils.

PMID- 21094084
TI  - Multiple effects of childhood deafness on cortical activity in children receiving
      bilateral cochlear implants simultaneously.
AB  - OBJECTIVE: Auditory development is disrupted without normal hearing but might
      proceed to some extent depending on the type and onset of deafness. We therefore
      hypothesized that activity in the auditory cortex would be highly variable in
      children who are deaf. METHODS: To answer this, activity in the deaf brain was
      evoked by electrical pulses from newly provided bilateral cochlear implants (CIs)
      in 72 children (n=144 responses). RESULTS: Responses were categorized by visual
      inspection into 3 main types which were validated by principal component cluster
      analyses; 49% had a negative amplitude wave similar to that previously reported
      in pre-term infants, 26% were dominated by a positive peak typical of responses
      in young normal hearing children and experienced paediatric CI users, 25% were
      novel multi-peaked responses. No significant demographic differences, including
      duration and onset of deafness, were found between response types. However,
      children with severe biallelic mutations of GJB-2 showed predominately negative
      peak type responses (79%) as compared with their peers without these mutations
      who had a more equal distribution between cortical response types. CONCLUSION:
      Cortical development in children who are deaf is heterogeneous but can be better
      predicted when the genotype is known to be a GJB-2 mutation. SIGNIFICANCE:
      Remediation of childhood deafness seeks to restore normal development and
      function of central auditory functions and thus may need to be tailored to
      account for effects specific to the aetiology of deafness.

PMID- 21094086
TI  - Neck back and spine injuries in amateur rugby league: a review of nine years of
      Accident Compensation Corporation injury entitlement claims and costs.
AB  - Rugby league is a popular participation sport, but there have been concerns
      raised regarding the possible high number of severe neck, back and spine
      injuries. Therefore an epidemiological overview of rugby league neck, back and
      spine injuries and associated costs of these injuries was undertaken in one
      country over nine years. The New Zealand national Accident Compensation
      Corporation data for moderate to serious injury entitlement claims (MSC) over
      nine years were analysed for the number, type and cost of neck, back and spine
      rugby league injuries resulting in medical treatment. There were 206 (3%) neck,
      back and spine MSC claims totalling NZD$1,585,927 (4%) of the total injury
      entitlement costs for rugby league over the nine-year period. The rate of MSC
      neck, back and spine rugby league injuries was 26 per 1000 total rugby league
      claims. Although the rate of neck, back and spine injuries varied over the nine
      years from 22 to 40 per 1000 injury claims, there was a significant increase over
      the duration of the study in the number of neck, back and spine MSC claims
      (chi2=849, df=8, p<0.001), and the cost per MSC injury claim (chi2=19,054, df=8,
      p<0.001). The frequency, severity and first 12 months cost of neck, back and
      spine injuries in rugby league is an issue that needs to be addressed.
      Unfortunately the ACC data base does not provide information on how or why the
      injuries occurred. A prospective injury epidemiology study needs to be conducted
      that will allow collection of information surrounding the mechanisms of injury
      and possible causative risk factors such as tackling technique. In the meantime
      it is suggested that coaches should ensure tackling technique is correctly taught
      to all rugby league players to reduce the risk of neck, back and spine injury.
      Team medical personnel should be trained in dealing with neck and spine injuries
      as well as head related injuries, and emergency procedures in dealing with
      players with a suspected neck or back injury should be practiced at clubs.

PMID- 21094085
TI  - Thermophilic two-stage dry anaerobic digestion of model garbage with ammonia
      stripping.
AB  - To avoid the inhibition of methane production by ammonia that occurs during the
      degradation of garbage, anaerobic digestion with prior ammonia production and
      subsequent stripping was investigated. In the ammonia production phase, the
      maximum ammonia concentration was approximately 2800 mg N/kg of total wet sludge
      in the range of 4 days of sludge retention time, indicating that only 43% of
      total nitrogen in the model garbage was converted to ammonia. The model garbage
      from which ammonia was produced and stripped was subjected to semi-continuous
      thermophilic dry anaerobic digestion over 180 days. The gas yield was in the
      range of 0.68 to 0.75 Nm(3)/kg volatile solid, and it decreased with the decrease
      of the sludge retention time. The ammonia-nitrogen concentration in the sludge
      was kept below 3000 mg N/kg total wet sludge. Microbial community structure
      analysis revealed that the phylum Firmicutes dominated in the ammonia production,
      but the community structure changed at different sludge retention times. In dry
      anaerobic digestion, the dominant bacteria shifted from the phylum Thermotogae to
      Firmicutes. The dominant archaeon was the genus Methanothermobacter, but the
      ratio of Methanosarcina increased during the process of dry anaerobic digestion.

PMID- 21094087
TI  - Family members of patients with cancer: what they know, how they know and what
      they want to know.
AB  - BACKGROUND: Recent changes in healthcare management generally and in cancer care
      in particular, indicate a major shift in the clinical management of cancer from
      hospitals and healthcare professionals (HCPs) to patients and families. In light
      of these changes national and international policies and reports by the
      Department of Health and Children (2001, 2006) and the World Health Organisation
      (2004) have recommended that HCPs support family members (FMs) to care for loved
      ones. The purpose of this review therefore was to explore the extent to which
      FMs' needs are realised by HCPs in practice. OBJECTIVES: To examine recent
      research (2000-2010) in relation to; the type of information that FMs of patients
      with cancer generally seek, how they seek this information from HCPs, and, FMs'
      experiences of communicating with HCPs in this context. METHODS: A review of the
      literature was conducted using key databases Medline, Pub med, Psych-Info and
      CINAHL. RESULTS: Thirty four papers were included in the review. Overall the
      studies demonstrated that FMs of patients with cancer have similar information
      needs and demonstrate similar strategies for seeking information. While many FMs
      report positive communication experiences with HCPs and have information needs
      met, the majority of FMs report negative communication encounters with HCPs.
      CONCLUSION: HCPs are highly significant in the lives of FMs of patients with
      cancer. The review concludes with identifying; FMs most wanted information needs,
      their struggles with accessing HCPs and the type of communication encounters FMs
      most desire to have with HCPs. Recommendations for education, practice and
      research are addressed.

PMID- 21094088
TI  - Women's help seeking behaviour for self discovered breast cancer symptoms.
AB  - PURPOSE OF THE RESEARCH: The aim of the study was to explore women's Help Seeking
      Behaviour (HSB) for a self discovered breast symptom, in order to gain
      understanding of women's experience of finding a breast symptom and how this
      influenced their HSB. In addition, the study sought to confirm the
      appropriateness of the "Help Seeking Behaviour & Influencing Factors" framework,
      for use in phase two of the study. METHODS AND SAMPLE: A qualitative descriptive
      method was used involving semi-structured interviews with ten women, ranging in
      age from 25 to 55 years, who had discovered a breast symptom. KEY RESULTS:
      Women's HSB ranged from up to one month (n = 6), one to three months (n = 2) and
      over three months (n = 2), following symptom discovery. The key variables linked
      to delayed help seeking were denial, fear, social factors and knowledge and
      beliefs. The study verified that the variables within the "Help Seeking Behaviour
      and Influencing Factors" framework act as both facilitators and barriers to
      women's HSB. Thus, confirming the appropriateness of this framework for a larger
      quantitative study of women's help seeking behaviour. CONCLUSIONS: The study
      highlights that despite continued emphasis on early help seeking for breast
      cancer symptoms, delay is still prevalent amongst women. This reiterates the need
      for continued emphasis on the message of early detection for breast cancer
      symptoms. To this end, nurses have a significant role to play in educating women
      in both clinical and community settings, about breast cancer and early detection
      practices.

PMID- 21094090
TI  - The catcher in the why: developing an evidence-based approach to the
      organization, delivery and evaluation of pre-registration nurse educational
      programmes.
AB  - Changes to the pedagogy of pre-registration nurse education and training have
      become a global phenomenon. However, the evidence base to inform responses to
      these changes and the impact on nursing practice is limited. This paper explores
      the outcomes of an innovative approach aimed at ensuring responses to these
      drivers for change, particularly in curriculum development, the organisation,
      management and delivery of programmes and the enhancement of the student
      experience, are evidence based. This paper reports on an organisational change
      project undertaken in a School of Nursing in the North West of England, UK. The
      project involved 12 interrelated work streams used to explore aspects of the
      student journey from recruitment through progression to eventual employment. An
      evidence base was developed through a methodological bricolage that drew upon a
      robust and authentic mixture of systematic literature reviews, contemporaneous
      analysis of educational practice and evaluation of the student experience. This
      was used to underpin the decision making processes required to promote innovation
      in programme design, to increase the involvement of students in the facilitation
      and evaluation of their learning experiences, and helped shape the organisational
      changes required for embedding an evidenced-based culture in the School.
      Consistent and transformational leadership has been key to the project's success
      in communicating and managing the changes.

PMID- 21094089
TI  - Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid
      malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics,
      pharmacodynamics, and antitumour activity.
AB  - BACKGROUND: Proteins of the BCL-2 family regulate clonal selection and survival
      of lymphocytes, and are frequently overexpressed in lymphomas. Navitoclax is a
      targeted high-affinity small molecule that inhibits the anti-apoptotic activity
      of BCL-2 and BCL-XL. We aimed to assess the safety and antitumour activity of
      navitoclax in patients with lymphoid tumours, and establish the drug's
      pharmacokinetic and pharmacodynamic profiles. METHODS: In this phase 1 dose
      escalation study, patients (aged >=18 years) with relapsed or refractory lymphoid
      malignancies were enrolled and treated at seven sites in the USA between
      November, 2006, and November, 2009. A modified Fibonacci 3+3 design was used to
      assign patients to receive oral navitoclax once daily by one of two dosing
      schedules: intermittently for the first 14 days of a 21-day cycle (14/21) at
      doses of 10, 20, 40, 80, 110, 160, 225, 315, or 440 mg/day; or continuously for
      21 days of a 21-day cycle (21/21) at doses of 200, 275, 325, or 425 mg/day. Study
      endpoints were safety, maximum tolerated dose, pharmacokinetic profile,
      pharmacodynamic effects on platelets and T cells, and antitumour activity. This
      trial is registered with ClinicalTrials.gov, number NCT00406809. FINDINGS: 55
      patients were enrolled (median age 59 years, IQR 51-67), 38 to receive the 14/21
      dosing schedule, and 17 to receive the 21/21 dosing schedule. Common toxic
      effects included grade 1 or 2 anaemia (41 patients), infection (39), diarrhoea
      (31), nausea (29), and fatigue (21); and grade 3 or 4 thrombocytopenia (29),
      lymphocytopenia (18), and neutropenia (18). On the intermittent 14/21 schedule,
      dose-limiting toxic effects were hospital admissions for bronchitis (one) and
      pleural effusion (one), grade 3 increase in aminotransferases (one), grade 4
      thrombocytopenia (one), and grade 3 cardiac arrhythmia (one). To reduce platelet
      nadir associated with intermittent 14/21 dosing, we assessed a 150 mg/day lead-in
      dose followed by a continuous 21/21 dosing schedule. On the 21/21 dosing
      schedule, two patients did not complete the first cycle and were excluded from
      assessment of dose-limiting toxic effects; dose-limiting toxic effects were grade
      4 thrombocytopenia (one), grade 3 increase in aminotransferases (one), and grade
      3 gastrointestinal bleeding (one). Navitoclax showed a pharmacodynamic effect on
      circulating platelets and T cells. Clinical responses occurred across the range
      of doses and in several tumour types. Ten of 46 patients with assessable disease
      had a partial response, and these responders had median progression-free survival
      of 455 days (IQR 40-218). INTERPRETATION: Navitoclax has a novel mechanism of
      peripheral thrombocytopenia and T-cell lymphopenia, attributable to high-affinity
      inhibition of BCL-XL and BCL-2, respectively. On the basis of these findings, a
      150 mg 7-day lead-in dose followed by a 325 mg dose administered on a continuous
      21/21 dosing schedule was selected for phase 2 study. FUNDING: Abbott
      Laboratories, Genentech, and National Cancer Institute, National Institutes of
      Health.

PMID- 21094091
TI  - An international consensus classification for focal cortical dysplasias.

PMID- 21094092
TI  - SARS--my personal battle.
AB  - It isn't every day that a doctor becomes a patient. It is more peculiar when it
      occurs with an unknown mysterious epidemic respiratory illness that kills. Severe
      acute respiratory syndrome (SARS) gripped the world in 2003, spreading via air
      links and throwing the global economy into disarray. As a practicing physician in
      Singapore, one of the first countries affected, I describe my first-hand account
      of my battle with this illness, how I acquired this illness in Singapore, and
      eventually quarantine in Frankfurt am Main, Germany.

PMID- 21094093
TI  - Maternal self-efficacy in the home food environment: a qualitative study among
      low-income mothers of nutritionally at-risk children in an urban area of Jakarta,
      Indonesia.
AB  - OBJECTIVE: To explore the factors that encompass maternal self-efficacy in
      providing food for the home. METHODS: In-depth interviews were conducted with 19
      mothers of nutritionally at risk children in an urban area of East Jakarta,
      Indonesia. This study was based on Social Cognitive Theory, Family Stress Models,
      and Ecological Frameworks. Data collection was coded and analyzed using the
      Grounded Theory Method. RESULTS: Most mothers felt secure in providing food for
      their families knowing that their relatives and neighbors would support them if
      they lacked the money to buy food; however, most of them did not supply
      appropriate meals in terms of nutrient content, variety, and timing. CONCLUSIONS
      AND IMPLICATIONS: Maternal self-efficacy was mainly characterized by practical
      issues concerning the preparation of food at home and a lack of knowledge of
      health and nutrition. Family-based interventions are needed to enhance competence
      in providing nutritious food from available resources.

PMID- 21094094
TI  - Circulating cytokines are associated with human islet graft function in type 1
      diabetes.
AB  - Islet cell transplantation has considerable potential as a cure for type 1
      diabetes, but recurrent autoimmunity and allograft rejection in which both
      cytokines play an important role are major obstacles. Using a new approach
      considering confounders by regression analysis, we investigated circulating
      cytokines and their association with graft function in type 1 diabetes patients
      who underwent either simultaneous islet kidney (SIK) or islet after kidney (IAK)
      transplantation. After transplantation, interleukin (IL)-10 was lower in SIK
      recipients with subsequent loss of graft function in comparison to recipients
      maintaining graft function. Before transplantation, high IL-13 and IL-18
      concentrations were prospectively associated for subsequent loss of graft
      function in IAK recipients, whereas in SIK recipients, high macrophage migration
      inhibitory factor (MIF) concentrations were associated with subsequent loss of
      graft function. Circulating cytokines are associated with islet graft function in
      patients with long-standing type 1 diabetes when considering confounders.

PMID- 21094095
TI  - Preconception care for women with diabetes: is it effective and who should
      provide it?
AB  - The association between hyperglycaemia and congenital malformations was first
      recognised over 40 years ago and was followed by the development of preconception
      clinics for women with diabetes. A fresh look at preconception care is needed as
      many studies were conducted during the late 1970s and early 1980s, before the
      introduction of regular home blood glucose monitoring and glycosylated
      haemoglobin assays, and when many patients with diabetes had microvascular
      complications. Recent observational studies and a meta-analysis suggest
      preconception care is effective with an approximately threefold reduction in the
      risk of malformations. There is now a worldwide epidemic of type 2 diabetes, but
      only few studies of preconception care have included women with type 2 diabetes.
      Furthermore, few studies have addressed the relationship between preconception
      care and perinatal morbidity. This article will review the evidence for
      preconception care in women with diabetes, evaluate different models of
      preconception care and discuss future strategies.

PMID- 21094096
TI  - Conflicting disclosure of conflicts of interest among spine societies: a cause
      for concern or an opportunity to evolve?

PMID- 21094097
TI  - Use of bidirectional barbed suture in laparoscopic myomectomy: evaluation of
      perioperative outcomes, safety, and efficacy.
AB  - STUDY OBJECTIVE: To compare perioperative outcomes during laparoscopic myomectomy
      using a bidirectional barbed suture vs conventional smooth suture. DESIGN:
      Retrospective analysis of 138 consecutive laparoscopic myomectomies performed by
      a single surgeon over 3 years (Canadian Task Force classification II-2). SETTING:
      Major university teaching hospital. PATIENTS: One hundred thirty-eight women with
      symptomatic uterine myomas. INTERVENTIONS: In women undergoing laparoscopic
      myomectomy from February 2007 through April 2010, conventional smooth sutures
      were used in 31 patients, and bidirectional barbed suture in 107 patients.
      MEASUREMENTS AND MAIN RESULTS: The primary indications for laparoscopic
      myomectomy in either group were pelvic pain or pressure and abnormal uterine
      bleeding. Use of bidirectional barbed suture was found to significantly shorten
      the mean (SD) duration of surgery (118 [53] minutes vs 162 [69] minutes; p <.05)
      and reduce the duration of hospital stay (0.58 [0.46] days vs 0.97 [0.45] days; p
      <.05). No significant differences were observed between the 2 groups insofar as
      incidence of perioperative complications, estimated blood loss, and number or
      weight of myomas removed during surgery. CONCLUSION: Use of bidirectional barbed
      suture seems to facilitate closure of the hysterotomy site in laparoscopic
      myomectomy.

PMID- 21094098
TI  - Modifications of laparoscopic supracervical hysterectomy technique significantly
      reduce postoperative spotting.
AB  - STUDY OBJECTIVE: The aim of this study was to estimate the benefit of excision of
      the endocervix during laparoscopic supracervical hysterectomy (LSH) with regard
      to postoperative cyclical bleeding. DESIGN: Cohort study from 2 centers (Canadian
      Task Force classification II-2). SETTING: Two surgical teams at the University of
      Duesseldorf Medical Center and PAN Clinic, Cologne, Germany. PATIENTS: Women with
      menstrual bleeding disorders resistant to medical treatment, symptomatic
      leiomyomata, dysmenorrhea. INTERVENTION: Laparoscopic supracervical hysterectomy.
      The uterus was transsected from the cervix with 2 techniques with and without
      excision of cervical canal. MEASUREMENTS AND MAIN RESULTS: We evaluated 300
      patients who underwent consecutive LSH procedures. In 150 patients the uterus was
      transsected from the cervix using a monopolar loop. In a second series of 150
      patients a unipolar needle electrode was used for the uterine amputation and the
      excision of cervical canal. The mean duration of the transsection was 65 seconds
      (monopolar loop) versus 168 seconds (monopolar needle). The excision of the
      endocervix was performed without any complications in 148 procedures. Histologic
      examination of the removed tissue revealed endocervical tissue in 83.3% (n =
      125), endometrium in 9.4% (n = 14), cervicoisthmic mucosa in 3.3% (n = 5), and
      myometrium only in 4% (n = 4). All 300 patients were contacted 12 months after
      surgery to inquire about bleeding status, and 282 (94%) responded. In patients
      who underwent excision of the endocervix, postoperative cyclical bleeding was
      significantly reduced compared with the control group (1.4% vs 10.7%).
      CONCLUSION: The results of this study indicate that the routine excision of the
      endocervix is a quick safe procedure which allows a significant reduction of
      postoperative cyclical bleeding in patients who undergo LSH.

PMID- 21094099
TI  - Comparison of lignocaine gel-soaked Falope rings vs rectal diclofenac suppository
      for pain relief in laparoscopic sterilization.
AB  - STUDY OBJECTIVE: To compare the analgesic efficacy of lignocaine gel-soaked
      Silastic bands compared with rectal diclofenac suppositories in patients
      undergoing interval laparoscopic sterilization under conscious sedation. DESIGN:
      Prospective, randomized, controlled, single-blinded, clinical trial. SETTING: Day
      case center in a tertiary care hospital in India. PATIENTS: Ninety-six women
      undergoing interval laparoscopic sterilization using Silastic bands (Yoon rings)
      randomly allocated by computer-generated random numbers into 3 groups.
      INTERVENTIONS: All women received intravenous sedation with injection diazepam
      and pentazocine along with local infiltration lignocaine injected at the site of
      the incision meant for insertion of the single site laparocator. In group 1 (n =
      32), the Silastic bands (Falope rings) were presoaked in 2% sterile lignocaine
      gel; in group 2 (n = 32), women received a 100-mg rectal diclofenac suppository
      while on the operating table; and women in group 3 received only conventional
      analgesic. Pain perception was assessed using an 11-point visual analog score
      just after the procedure while still on the table (zero minutes), at 30 minutes
      and 1 hour after the procedure, and at discharge. MEASUREMENTS AND MAIN RESULTS:
      The women in all 3 groups were comparable insofar as age and parity. At zero
      minutes (while on the operating table), the pain score in all 3 groups was
      similar. However, the pain scores at 30 and 60 minutes, and at discharge were
      significantly lower in groups 1 and group 2 compared with group 3. However, 2
      women (6.25%) in group 2 and 6 (18.75%) in group 3 required supplemental
      analgesia within 1 hour, and were administered a 500-mg oral dose of mefenamic
      acid. The need for further analgesia was significantly lower in groups 1 and 2
      compared with group 3 (p = .02). Comparison of groups 1 and 3 revealed that in
      group 1, the pain scores were significantly lower at 30 minutes (p = .02), 1 hour
      (p = .005), and at discharge (p = .004). No patients in group 1 requested
      analgesia, whereas 6 women in group 3 asked for further analgesia within an hour
      postoperatively (p = .01). Similarly in groups 2 and 3, women who received
      diclofenac suppositories had significantly lower pain scores at the specified
      intervals (p = 0.02, 0.002, and 0.02, respectively). CONCLUSION: Application of
      lignocaine gel to Falope rings and preoperative insertion of a rectal diclofenac
      suppository are simple and effective measures for pain control in the early
      postoperative period in patients undergoing day-case laparoscopic sterilization
      under conscious sedation. Either method could be incorporated into routine
      practice, depending on patient and physician choice.

PMID- 21094100
TI  - An examination of pentafluorobenzoyl derivatization strategies for the analysis
      of fatty alcohols using gas chromatography/electron capture negative ion chemical
      ionization-mass spectrometry.
AB  - Gas chromatography/electron capture negative ion chemical ionization-mass
      spectrometry (GC/ECNICI-MS) combined with pentafluorobenzoyl derivatization
      (PFBoyl) is frequently used for the sensitive detection of fatty alcohols (FOH).
      However, this derivatization technique suffers from a lack of established
      reaction protocols, time-consuming reactions, and the presence of reagent
      artifacts or unwanted derivatization by-products which can hinder analyte
      detection. Here, strategies are presented to reduce the problems associated with
      PFBoyl-derivatization, including (1) the optimization of reaction conditions
      (derivatization time and temperature) for a variety of PFBoyl-derivatized FOH,
      (2) an investigation of microwave-accelerated derivatization (MAD) as a rapid
      alternative heating mechanism for the PFBoyl-derivatization of FOH, and (3) an
      analysis of an alternative strategy employing a solvent extraction procedure post
      derivatization to reduce the detrimental effects commonly associated with PFBoyl
      derivatization reagents. The optimal reaction conditions for the PFBoyl
      derivatization of FOH were determined to be 60 degrees C for 45 min. The
      investigation in MAD demonstrated the potential of obtaining comparable PFBoyl
      derivatizations to those obtained using traditional heating methods, albeit in a
      reaction time of 3 min. An examination of several solvents for post
      derivatization extraction revealed improved relative response factors in
      comparison to those obtained without solvent extraction. The best solvents for
      the PFBoyl-FOH extraction, dichloromethane and tert-butyl methyl ether, were also
      compared to the no solvent extraction samples with standard response curves and
      PFBoyl-derivatized FOH in Bligh-Dyer extracted rat plasma.

PMID- 21094101
TI  - An ultra performance liquid chromatography-tandem MS assay for tamoxifen
      metabolites profiling in plasma: first evidence of 4'-hydroxylated metabolites in
      breast cancer patients.
AB  - There is increasing evidence that the clinical efficacy of tamoxifen, the first
      and most widely used targeted therapy for estrogen-sensitive breast cancer,
      depends on the formation of the active metabolites 4-hydroxy-tamoxifen and 4
      hydroxy-N-desmethyl-tamoxifen (endoxifen). Large inter-individual variability in
      endoxifen plasma concentrations has been observed and related both to genetic and
      environmental (i.e. drug-induced) factors altering CYP450s metabolizing enzymes
      activity. In this context, we have developed an ultra performance liquid
      chromatography-tandem mass spectrometry method (UPLC-MS/MS) requiring 100 MUL of
      plasma for the quantification of tamoxifen and three of its major metabolites in
      breast cancer patients. Plasma is purified by a combination of protein
      precipitation, evaporation at room temperature under nitrogen, and reconstitution
      in methanol/20 mM ammonium formate 1:1 (v/v), adjusted to pH 2.9 with formic
      acid. Reverse-phase chromatographic separation of tamoxifen, N-desmethyl
      tamoxifen, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen is performed
      within 13 min using elution with a gradient of 10 mM ammonium formate and
      acetonitrile, both containing 0.1% formic acid. Analytes quantification, using
      matrix-matched calibration samples spiked with their respective deuterated
      internal standards, is performed by electrospray ionization-triple quadrupole
      mass spectrometry using selected reaction monitoring detection in the positive
      mode. The method was validated according to FDA recommendations, including
      assessment of relative matrix effects variability, as well as tamoxifen and
      metabolites short-term stability in plasma and whole blood. The method is precise
      (inter-day CV%: 2.5-7.8%), accurate (-1.4 to +5.8%) and sensitive (lower limits
      of quantification comprised between 0.4 and 2.0 ng/mL). Application of this
      method to patients' samples has made possible the identification of two further
      metabolites, 4'-hydroxy-tamoxifen and 4'-hydroxy-N-desmethyl-tamoxifen, described
      for the first time in breast cancer patients. This UPLC-MS/MS assay is currently
      applied for monitoring plasma levels of tamoxifen and its metabolites in breast
      cancer patients within the frame of a clinical trial aiming to assess the impact
      of dose increase on tamoxifen and endoxifen exposure.

PMID- 21094102
TI  - Towards slide enhancement with the titanium-molybdenum wire?
AB  - This study aims to improve the tribological properties of titanium-molybdenum
      wire. Following an analysis of the wire/bracket/ligation friction parameters and
      an overview of the technological research into means of reducing such friction,we
      set up several types of surface treatment in the laboratory by physical
      deposition in the vapor phase and using cold plasma technology. The specimens
      obtained underwent two types of tribological tests and were then subjected to
      traction and bending tests in order to determine the variations in their
      mechanical properties induced by the different types of treatment. For purposes
      of comparison, all the tests were conducted on untreated wire, TMA(r) Low
      friction(r) wire and stainless steel wire and with two types of elastomeric ties.
      We were able to demonstrate some remarkable slide performances obtained using
      cold plasma nitriding while preserving the mechanical properties. A significant
      difference was observed relative to the other surface treatments.

PMID- 21094105
TI  - Impact of genioplasty on mandibular growth during puberty.
AB  - AIM: Genioplasty has been validated for the correction of mandibular vertical
      excess and is generally performed at the end of the growth period, either alone
      or in association with other forms of osteotomy. Our aim was to assess whether
      genioplasty performed at an earlier age can impact mandibular growth. METHODS:
      This comparative prospective study included 25 high-angle, mouth-breathing
      adolescents following orthodontic and ENT treatment. Subjects were divided into
      two groups according to their stage of puberty, either early (group 1: Tanner's
      stage 3, n=12) or late stage (group 2: Tanner stage 4-5, n=13). Genioplasty was
      performed in both groups. Cephalometric comparison was made on the overall
      population and for each group, before and after genioplasty (at 1, 6, 12 and
      18months). RESULTS: In the immediate postoperative period, significant variation
      of all the cephalometric measures was observed within each group showing
      reduction of the vertical dimension and sagittal augmentation. Eighteen months
      post-surgery, only group 1 exhibited a significant increase in SNPog.
      Augmentation of the SNB and anterior mandibular rotation were also significantly
      greater in group 1. The difference in the direction of growth of the mandible
      before genioplasty (18months of orthodontics) and postgenioplasty (18months of
      postoperative monitoring) was also significant. CONCLUSION: Early genioplasty
      permits redirection of mandibular growth conducive to orthopedic correction of
      high angle Class II.

PMID- 21094107
TI  - Influence of the mode of nutritive and non-nutritive sucking on the dimensions of
      primary dental arches.
AB  - INTRODUCTION: Sucking is innate in both infants and young children. It is termed
      nutritive when referring to suckling from the breast or bottle-feeding and non
      nutritive when applied to sucking of a digit or pacifier. Few studies have
      attempted to assess the impact of the type of sucking on the size of the dental
      arches. The aim of this study was to quantify the influence of the mode of
      nutritive suckling and non-nutritive sucking habits (NNSH) on the measurements of
      the dental arches. PATIENTS AND METHODS: This was a transverse descriptive study
      involving 226 Senegalese children. The mode of feeding and the presence or not of
      a NNSH (digit or pacifier) were gathered from parents of all children using a
      structured questionnaire. Quantitative variables regarding intra- and inter-arch
      relationships were recorded using plaster moulds taken from the children.
      Statistical analyses were used to compare the different variables according to
      gender, the mode of feeding and the presence or not of a NNSH. RESULTS: The
      subjects in the study (123 boys and 103 girls) were aged between 5 and 6years
      old. The children who had enjoyed mixed feeding (breast/bottle combination) had a
      great length of the anterior maxillary arch and a significantly greater depth of
      the palatal arch than children receiving breast-feeding alone. The children with
      antecedents or a current NNSH had a longer anterior maxillary arch than subjects
      with no NNSH (P=0.01). Regarding inter-arch relationships, the children with
      antecedents or a current digit-sucking habit had less overbite than their peers
      who had no NNSH (P=0.04). CONCLUSION: The results of this study show that bottle
      feeding, even partial, as well as NNSH are associated with changes in certain
      dimensions of the maxillary dental arch and in inter-arch relationships.
      Longitudinal studies are required to investigate further the nature of this
      association.

PMID- 21094108
TI  - Y-STR Frequency Surveying Method: A critical reappraisal.
AB  - Reasonable formalized methods to estimate the frequencies of DNA profiles
      generated from lineage markers have been proposed in the past years and were
      discussed in the forensic community. Recently, collections of population data on
      the frequencies of variations in Y chromosomal STR profiles have reached a new
      quality with the establishment of the comprehensive neatly quality-controlled
      reference database YHRD. Grounded on such unrivalled empirical material from
      hundreds of populations studies the core assumption of the Haplotype Frequency
      Surveying Method originally described 10 years ago can be tested and improved.
      Here we provide new approaches to calculate the parameters used in the frequency
      surveying method: a maximum likelihood estimation of the regression parameters
      (r(1), r(2), s(1) and s(2)) and a revised Frequency Surveying framework with
      variable binning and a database preprocessing to take the population sub
      structure into account. We found good estimates for 11 metapopulations using both
      approaches and demonstrate that the statistical basis of the method is well
      supported and independent of the population under study. The results of the
      estimation process are reliable and robust if the underlying datasets are large
      and representative and show small average and pairwise genetic distances.

PMID- 21094109
TI  - Spinal cord compression due to C4 vertebral arch osteochondroma.
AB  - Osteochondromas are usually benign bone tumors found on the metaphysis of long
      bones. These tumors are rarely located on the spine especially at cervical level.
      This report presents the case of a 23-year-old man who had previously developed
      tetraparesis at the age of 13 after infectious myelitis. Recent severe clinical
      neurological deterioration revealed the diagnosis of osteochondroma arising in
      the C4 vertebral arch compressing the spinal cord and associated with
      syringomyelia. Of note in his past history was a treated hip localization. The
      patient underwent complete surgical excision of the osteochondroma. Postoperative
      outcome was good with slow clinical recovery from the spinal cord compression. We
      report this rare cause of spinal cord compression and other cases reported in the
      literature.

PMID- 21094110
TI  - Diagnosis and treatment of osteoporosis in spinal cord injury patients: A
      literature review.
AB  - OBJECTIVE: To present an up-to-date literature review of osteoporosis in spinal
      cord injury (SCI) patients, in view of the seriousness of this complication (with
      a high risk of fractures) and the complexity of its diagnosis, evaluation and
      treatment. METHODS: A Medline search with the following keywords: immobilization
      osteoporosis, spinal cord injury, bone loss, dual energy X-ray absorptiometry
      (DEXA), bisphosphonate. RESULTS: Our analysis of the literature noted a bone
      metabolism imbalance in SCI patients, with accelerated early bone resorption
      (particularly during the first 6 months post-injury). Although dual energy X-ray
      absorptiometry constitutes the "gold standard" diagnostic method, the decrease in
      bone mineral density only becomes significant 12 months after the injury.
      Bisphosphonate therapy has proven efficacy. Despite the frequent use of various
      physical therapies, these methods have not been found to be effective.
      CONCLUSION: Although our literature review did not identify any guidelines on the
      strategy for diagnosing and treating osteoporosis in SCI patients, several
      findings provide guidance on procedures for early diagnosis and preventive
      treatment.

PMID- 21094111
TI  - Plasma levels of resistin-like molecule beta in humans.
AB  - BACKGROUND: Resistin-like molecules (RELM) are expressed in many tissues and
      among those, RELMbeta is most abundantly expressed in the colon. Based on animal
      studies, RELMbeta is induced by high fat diets, obesity, and intestinal
      microflora and may play a role in insulin resistance and intestinal inflammation.
      In the present study, we evaluated whether RELMbeta could be measured in human
      plasma and the influence of selected host and behavioral factors on RELMbeta
      levels, including known risk factors for colorectal cancer. METHODS: The subjects
      for this pilot study were derived from healthy controls who participated in a
      population-based case-control study of colorectal cancer in Metropolitan Detroit.
      The subjects were 45-80 years of age without history of cancer or colorectal
      resection. RESULTS: RELMbeta was present in human plasma, with levels in the
      range of 0.08-0.26 ng/mL. Lower RELMbeta levels were found in subjects with non
      Caucasian race, lower pack-years of smoking, and higher physical activity index
      scores. Other variables such as dietary intakes, gender, obesity, use of non
      steroidal anti-inflammatory agents and history of polyps were not associated with
      RELMbeta levels. CONCLUSIONS: The direct association of RELMbeta with smoking and
      inverse association with physical activity, both of which are risk factors for
      colon cancer, indicates that RELMbeta may be involved in mediating the effects of
      these two lifestyle factors on risk of colon cancer.

PMID- 21094113
TI  - Surgical treatment of recurring subareolar abscess using oncoplastic techniques.
AB  - PURPOSE: To evaluate the clinical and cosmetic results of our treatment of
      recurrent periareolar abscess. PATIENTS AND METHODS: Our technique was applied to
      27 patients with recurrent periareolar abscess who had been previously surgically
      treated three or more times between January 2001 and December 2008. Our treatment
      combined resection of the fistula, the terminal milk ducts, and mammary gland
      involved in the inflammatory process. This was associated with glandular
      remodeling and a lift of the periareolar skin. Long-term clinical results and
      evaluation of cosmetic result are analyzed. RESULTS: The median age of patients
      was 36 years and the median course of disease was 5 years (2-11 years). The
      duration of follow-up was 37 months. Before being treated in our service,
      patients had a median of four prior surgeries for this condition (3-12). The
      average hospital stay was 3.2+/-0.6 days after surgery. One recurrence occurred
      among the 24 patients reviewed. She was treated by excision of the nipple and
      areola. Six patients (25%) rated their outcome excellent and 13 patients (54%)
      considered their results good. Five patients assessed their overall result as
      fair (21%), and no patients judged their results as poor. CONCLUSIONS: Our
      technique is simple and feasible and the results are encouraging. It can be used
      regardless of the location of the fistula around the periphery of the nipple
      areola complex and it is perfectly suited to the management of chronic fistulous
      abscess.

PMID- 21094112
TI  - Genetic polymorphisms of CYP17A1, vitamin D receptor and androgen receptor in
      Italian heredo-familial and sporadic prostate cancers.
AB  - BACKGROUND: Searching for genetic and environmental factors predisposing to
      prostate cancer, common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR
      genes, and the number of CAG repeats from AR were investigated in Italian heredo
      familial prostate cancer (HFPC) patients controlled for dietary intake and life
      style habits. METHODS: We evaluated differences between HFPC and sporadic
      cancers, in the pattern of common single-nucleotide polymorphisms in CYP17A1,
      CYP19A1, VDR genes, and the CAG repeat from AR, controlling for dietary intake
      and lifestyle habits in a regionwide population. Ninety-five patients with HFPC
      were identified and 378 sporadic prostate cancers were randomly selected as
      controls. Dietary intake and lifestyle habits were determined through self
      administered questionnaires in all patients. Genotyping of polymorphisms for
      CYP17A1, CYP19A1, VDR, and the CAG repeat from AR was carried out using
      pyrosequencing. RESULTS: HFPC cases were significantly younger than controls,
      whereas similar proportions of localized tumours, favourable histology, and
      abnormal prostate serum antigen levels (4-19 ng/ml) were detected in the two
      groups. A statistically evident gene-gene interaction was found: a 5-fold higher
      probability [odds ratio (OR)=4.83; 95% confidence interval (CI): 1.37-17.02] of
      HFPC was observed in the subgroup profiling VDR1 T/T genotypes coupled with VDR2
      T/T genotype. Among nutrients, an increase in HFPC risk (OR=3.14; 95% CI: 1.12
      8.81) was found only for zinc, when associated with the VDR2 T/T genotype.
      CONCLUSIONS: Significant evidence for positive interactions between VDR1 and VDR2
      genotypes was demonstrated, suggesting that high-risk multigenic polymorphism
      profiles could variously sustain HFPC tumorigenesis.

PMID- 21094114
TI  - CT myocardial perfusion imaging of myocardial blood flow reserve before and after
      coronary artery stenting.
AB  - A patient with crescendo angina underwent CTA, CTMPI and invasive angiography.
      Abnormal flow reserve was demonstrated in the RCA territory, which corresponded
      to a significant lesion demonstrated on CTA and invasive angiography. The defect
      was demonstrated prior to PCI, and resolved post PCI.

PMID- 21094115
TI  - Fungal pigments inhibit the matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry analysis of darkly pigmented fungi.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has been used to discriminate moniliaceous fungal species;
      however, darkly pigmented fungi yield poor fingerprint mass spectra that contain
      few peaks of low relative abundance. In this study, the effect of dark fungal
      pigments on the observed MALDI mass spectra was investigated. Peptide and protein
      samples containing varying concentrations of synthetic melanin or fungal pigments
      extracted from Aspergillus niger were analyzed by MALDI-TOF and MALDI-qTOF
      (quadrupole TOF) MS. Signal suppression was observed in samples containing
      greater than 250ng/MUl pigment. Microscopic examination of the MALDI sample
      deposit was usually heterogeneous, with regions of high pigment concentration
      appearing as black. Acquisition of MALDI mass spectra from these darkly pigmented
      regions of the sample deposit yielded poor or no [M+H](+) ion signal. In
      contrast, nonpigmented regions within the sample deposit and hyphal negative
      control extracts of A. niger were not inhibited. This study demonstrated that
      dark fungal pigments inhibited the desorption/ionization process during MALDI-MS;
      however, these fungi may be successfully analyzed by MALDI-TOF MS when culture
      methods that suppress pigment expression are used. The addition of tricyclazole
      to the fungal growth media blocks fungal melanin synthesis and results in less
      melanized fungi that may be analyzed by MALDI-TOF MS.

PMID- 21094116
TI  - Phosphoinositide-incorporated lipid-protein nanodiscs: A tool for studying
      protein-lipid interactions.
AB  - Phosphatidylinositol (PtdIns) is phosphorylated at D-3, D-4, and/or D-5 of the
      inositol ring to produce seven distinct lipid second messengers known as
      phosphoinositides (PIs). The PI level is temporally and spatially controlled at
      the cytosolic face of the cellular membrane. Effectors containing PI-binding
      domains (e.g., PH, PX, FYVE, ENTH, FERM) associate with specific PIs. This
      process is crucial for the localization of a variety of cell-signaling proteins,
      thereby regulating intracellular membrane trafficking, cell growth and survival,
      cytoskeletal organization, and so on. However, quantitative assessments of
      protein-PI interactions are generally difficult due to insolubility of PIs in
      aqueous solution. Here we incorporated PIs into a lipid-protein nanoscale bilayer
      (nanodisc), which is applied for studying the protein-PI interactions using pull
      down binding assay, fluorescence polarization, and nuclear magnetic resonance
      studies, each facilitating fast, quantitative, and residue-specific evaluation of
      the protein-PI interactions. Therefore, the PI-incorporated nanodisc could be
      used as a versatile tool for studying the protein-lipid interactions by various
      biochemical and biophysical techniques.

PMID- 21094117
TI  - Electrochemical determination of antihypertensive drug irbesartan in
      pharmaceuticals.
AB  - A sensitive voltammetric method has been developed for the determination of
      irbesartan in a Britton-Robinson buffer medium. Irbesartan exhibited a well
      defined cathodic peak over the entire pH range from 2.0 to 12.0. The mechanism of
      reduction was postulated on the basis of controlled potential electrolysis,
      coulometry, and spectral analysis. Under optimal conditions, a linear response of
      irbesartan was obtained in the range from 3.0 * 10(-5) to 5.7 * 10(-3)molL(-1)
      and with a limit of detection of 5.33 * 10(-7)molL(-1). The effect of cationic
      surfactant on the voltammetric reduction peak of irbesartan in Britton-Robinson
      buffer is also described.

PMID- 21094118
TI  - Probing cathepsin S activity in whole blood by the activity-based probe BIL-DMK:
      cellular distribution in human leukocyte populations and evidence of diurnal
      modulation.
AB  - Using the cell-permeable, radioiodinated, irreversible inhibitor BIL-DMK, we
      probed active cysteine cathepsins in blood. Incubation of the probe in human
      whole blood followed by separation of white blood cells by dextran sedimentation
      led to the labeling of one major band at 24kDa. Two-dimensional gel
      electrophoresis showed that the band resolved in a single protein spot and
      corresponded to cathepsin S based on its molecular mass, isoelectric point, and
      Western blot analysis using anti-human cathepsin S antibodies. Cathepsin S
      activity in human whole blood was dependent on the time of blood collection,
      suggesting that cathepsin S activity is subject to circadian variations.
      Separation of white blood cell populations using a magnetic cell sorter and
      further characterization by FACS (fluorescent-activated cell sorting) analysis
      demonstrated that the majority of active cathepsin S resided in the monocyte and
      neutrophil populations, whereas on a cell basis cathepsin S activity in
      granulocytes is 10-fold lower than that in monocytes. A whole blood cathepsin S
      assay was developed and used to measure cathepsin S inhibition in both in vitro
      and ex vivo conditions. To determine the correlation between the in vitro and ex
      vivo assays, a reversible cathepsin S inhibitor was dosed intravenously to a
      rhesus monkey. The inhibitor concentration required to inhibit 50% of the
      cathepsin S activity ex vivo correlated well with the concentration required to
      inhibit the enzyme in rhesus monkey whole blood in vitro. The results reported
      here demonstrate the utility of the activity-based probe BIL-DMK for the ex vivo
      assessment of cathepsin S inhibition.

PMID- 21094119
TI  - High-performance liquid chromatography ultraviolet assay for human erythrocytic
      catalase activity by measuring glutathione as o-phthalaldehyde derivative.
AB  - The most frequently used catalase (CAT) activity assay is based on the
      spectrophotometric measurement of hydrogen peroxide (H(2)O(2)) absorbance
      decrease at 240 nm. Here we report an alternative high-performance liquid
      chromatography (HPLC) assay for human erythrocytic CAT (heCAT) activity
      measurement based on glutathione (GSH) analysis as a highly stable, H(2)O(2)
      insensitive o-phthalaldehyde (OPA) derivative. The method was developed and
      validated using an isolated heCAT in phosphate-buffered saline at pH 7.4 and was
      applied to measure CAT activity in lysed human erythrocytes. heCAT activity was
      measured at initial concentrations of 5 nM for heCAT, 5mM for H(2)O(2), and 10mM
      for GSH, and the incubation time was 10 min. Nitrite (NO(2)(-)) was found to be
      an uncompetitive inhibitor of heCAT activity (IC(50)=9 MUM) and of CAT activity
      in hemolysate (IC(50)~750 MUM). Nitrate (NO(3)(-)) at concentrations up to 100
      MUM did not inhibit heCAT activity. Azide (N(3)(-)) was found to be a very strong
      inhibitor of the heCAT (IC(50)=0.2 nM) but a relatively weak CAT inhibitor
      (IC(50)~10 MUM) in human hemolysates. The novel CAT activity assay works under
      redox conditions that more closely resemble those prevailing in cells and allows
      high-throughput analysis despite the required HPLC step.

PMID- 21094120
TI  - Identification of 1- and 3-methylhistidine as biomarkers of skeletal muscle
      toxicity by nuclear magnetic resonance-based metabolic profiling.
AB  - Nuclear magnetic resonance (NMR)-based metabolomic profiling identified urinary 1
      and 3-methylhistidine (1- and 3-MH) as potential biomarkers of skeletal muscle
      toxicity in Sprague-Dawley rats following 7 and 14 daily doses of 0.5 or 1mg/kg
      cerivastatin. These metabolites were highly correlated to sex-, dose- and time
      dependent development of cerivastatin-induced myotoxicity. Subsequently, the
      distribution and concentration of 1- and 3-MH were quantified in 18 tissues by
      gas chromatography-mass spectrometry. The methylhistidine isomers were most
      abundant in skeletal muscle with no fiber or sex differences observed; however, 3
      MH was also present in cardiac and smooth muscle. In a second study, rats
      receiving 14 daily doses of 1mg/kg cerivastatin (a myotoxic dose) had 6- and 2
      fold elevations in 1- and 3-MH in urine and had 11- and 3-fold increases in 1-
      and 3-MH in serum, respectively. Selectivity of these potential biomarkers was
      tested by dosing rats with the cardiotoxicant isoproterenol (0.5mg/kg), and a 2
      fold decrease in urinary 1- and 3-MH was observed and attributed to the anabolic
      effect on skeletal muscle. These findings indicate that 1- and 3-MH may be useful
      urine and serum biomarkers of drug-induced skeletal muscle toxicity and
      hypertrophy in the rat, and further investigation into their use and limitations
      is warranted.

PMID- 21094121
TI  - Improved method for simultaneous isolation of proteins and nucleic acids.
AB  - Guanidinium thiocyanate-phenol-chloroform extraction (GTPC extraction) is widely
      used in molecular biology for isolating DNA, RNA, and proteins. Protein isolation
      by commercially available GTPC solutions is time consuming and the resulting
      pellets are only incompletely soluble. In this study ethanol-bromochloropropane
      water was used for precipitation of proteins from the phenol-ethanol phase after
      GTPC extraction of RNA and DNA. The precipitated proteins can be readily
      dissolved in 4% SDS for subsequent analysis. This technique allows a fast (30min)
      and efficient (with a protein recovery of up to 95%) extraction of proteins for
      the study of transcriptional and posttranscriptional events from the same sample.

PMID- 21094122
TI  - Noncovalent functionalization of carbon nanotubes with lectin for label-free
      dynamic monitoring of cell-surface glycan expression.
AB  - A kind of concanavalin A functionalized multiwalled carbon nanotube (ConA-MWCNT)
      was constructed by noncovalent assembly of ConA on carboxylated MWCNT with
      poly(diallyldimethylammonium) as a linker. The novel nanomaterial was
      characterized with scanning electron microscopy and atomic force microscopy. It
      incorporated both the specific recognition ability of lectin for cell-surface
      mannosyl groups and the unique electronic and mechanical properties of MWCNT. An
      electrochemical label-free method for cytosensing was proposed by constructing a
      ConA-MWCNT interface on a glassy carbon electrode, which showed a linear response
      to K562 cells ranging from 1 * 10(4) to 1 * 10(7) cellsmL(-1). The ConA-MWCNT
      interface could be further used for monitoring of dynamic variation of glycan
      expression on K562 cells in response to drugs. A facile and high-throughput
      optical method for the analysis of dynamic glycan expression on living cells was
      also developed by constructing an array of ConA-MWCNT spots on a glass slide.
      This method showed acceptable rapidity and low cost. The noncovalent
      functionalization of MWCNTs with lectins could be potentially applied in cell
      biological studies based on cell-surface glycan expression.

PMID- 21094123
TI  - An approach for differentiating uniform glutamatergic neurons from mouse
      embryonic stem cells.
AB  - Much effort is being marshaled to generate uniform neuronal populations from
      embryonic stem (ES) cells, but a completely reliable method has yet to be
      developed. Here we modified and established a method that brings us closer to
      this goal. By examining many parameters, we found that the optimal timing of
      applying a freshly made trypsin/EDTA (ethylenediaminetetraacetic acid) solution
      to dissociate embryoid bodies determines the success of the outcome. Analyses
      demonstrated that with this approach, more than 87% of cells differentiated into
      glutamatergic neurons. Hence, these uniform neurons that were differentiated from
      ES cells provide an ideal cellular model for many aspects of research.

PMID- 21094124
TI  - Green tea prevents non-melanoma skin cancer by enhancing DNA repair.
AB  - Excessive exposure of the skin to solar ultraviolet (UV) radiation is one of the
      major factors for the development of skin cancers, including non-melanoma. For
      the last several centuries the consumption of dietary phytochemicals has been
      linked to numerous health benefits including the photoprotection of the skin.
      Green tea has been consumed as a popular beverage world-wide and skin
      photoprotection by green tea polyphenols (GTPs) has been widely investigated. In
      this article, we have discussed the recent investigations and mechanistic studies
      which define the potential efficacy of GTPs on the prevention of non-melanoma
      skin cancer. UV-induced DNA damage, particularly the formation of cyclobutane
      pyrimidine dimers, has been implicated in immunosuppression and initiation of
      skin cancer. Topical application or oral administration of green tea through
      drinking water of mice prevents UVB-induced skin tumor development, and this
      prevention is mediated, at least in part, through rapid repair of DNA. The DNA
      repair by GTPs is mediated through the induction of interleukin (IL)-12 which has
      been shown to have DNA repair ability. The new mechanistic investigations support
      and explain the anti-photocarcinogenic activity, in particular anti-non-melanoma
      skin cancer, of green tea and explain the benefits of green tea for human health.

PMID- 21094125
TI  - C-terminal fragment of amebin promotes actin filament bundling, inhibits acto
      myosin ATPase activity and is essential for amoeba migration.
AB  - Amebin [formerly termed as ApABP-FI; Sobczak et al. (2007) Biochem. Cell Biol.
      85] is encoded in Amoeba proteus by two transcripts, 2672-nt and 1125-nt. A
      product of the shorter transcript (termed as C-amebin), comprising C-terminal 375
      amino-acid-residue fragment of amebin, has been expressed and purified as the
      recombinant GST-fusion protein. GST-C-amebin bound both to monomeric and
      filamentous actin. The binding was Ca(2+)-independent and promoted filament
      bundling, as revealed with the transmission electron microscopy. GST-C-amebin
      significantly decreased MgATPase activity of rabbit skeletal muscle acto-S1.
      Removal with endoproteinase ArgC of a positively charged C-terminal region of GST
      amebin containing KLASMWEQ sequence abolished actin-binding and bundling as well
      as the ATPase-inhibitory effect of C-amebin, indicating that this protein region
      was involved in the interaction with actin. Microinjection of amoebae with
      antibody against C-terminus of amebin significantly affected amoebae morphology,
      disturbed cell polarization and transport of cytoplasmic granules as well as
      blocked migration. These data indicate that amebin may be one of key regulators
      of the actin-cytoskeleton dynamics and actin-dependent motility in A. proteus.

PMID- 21094126
TI  - Crowding agents and osmolytes provide insight into the formation and dissociation
      of RNase A oligomers.
AB  - RNase A forms 3D domain-swapped oligomers with novel enzymatic and biological
      activities. We study how crowding agents and osmolytes affect the formation and
      dissociation of RNase A oligomers. The crowding agents Ficoll and dextran were
      found to enhance oligomer formation, whereas the stabilizers sodium sulfate,
      glycine and trimethylammonium oxide (TMAO) do not. In contrast, TMAO
      significantly slows RNase A dimer dissociation, while the effect of Ficoll is
      small. These results lead us to propose that the mechanisms of oligomer formation
      and dissociation are different. In the RNase A "C-dimer", the C-terminal beta
      strand is swapped between two subunits. The loop preceding this beta-strand
      adopts a beta-sheet which has been proposed to resemble amyloid structurally.
      Hydrogen/deuterium (H/D) exchange of the RNase A C-dimer reveal that the H-bonds
      formed between the swapped C-terminal beta-strand and the other subunit are
      strong. Their rupture may be crucial for C-dimer dissociation. In contrast, H
      bonds formed by Asn 113 in the novel beta-sheet adopted by the hinge loop in the
      C-dimer are not strongly protected. Besides the fundamental insights obtained,
      the results represent a technical advance for obtaining increased oligomer yields
      and storage lifetimes.

PMID- 21094127
TI  - Adenosine and its receptors in the heart: regulation, retaliation and adaptation.
AB  - The purine nucleoside adenosine is an important regulator within the
      cardiovascular system, and throughout the body. Released in response to
      perturbations in energy state, among other stimuli, local adenosine interacts
      with 4 adenosine receptor sub-types on constituent cardiac and vascular cells:
      A(1), A(2A), A(2B), and A(3)ARs. These G-protein coupled receptors mediate varied
      responses, from modulation of coronary flow, heart rate and contraction, to
      cardioprotection, inflammatory regulation, and control of cell growth and tissue
      remodeling. Research also unveils an increasingly complex interplay between
      members of the adenosine receptor family, and with other receptor groups. Given
      generally favorable effects of adenosine receptor activity (e.g. improving the
      balance between myocardial energy utilization and supply, limiting injury and
      adverse remodeling, suppressing inflammation), the adenosine receptor system is
      an attractive target for therapeutic manipulation. Cardiovascular adenosine
      receptor-based therapies are already in place, and trials of new treatments
      underway. Although the complex interplay between adenosine receptors and other
      receptors, and their wide distribution and functions, pose challenges to
      implementation of site/target specific cardiovascular therapy, the potential of
      adenosinergic pharmacotherapy can be more fully realized with greater
      understanding of the roles of adenosine receptors under physiological and
      pathological conditions. This review addresses some of the major known and
      proposed actions of adenosine and adenosine receptors in the heart and vessels,
      focusing on the ability of the adenosine receptor system to regulate cell
      function, retaliate against injurious stressors, and mediate longer-term adaptive
      responses.

PMID- 21094128
TI  - MAPK signaling in H9c2 cardiomyoblasts exposed to cholesterol secoaldehyde--role
      of hydrogen peroxide.
AB  - 3beta-Hydroxy-5,6-secocholestan-6-al (cholesterol secoaldehyde or ChSeco), an
      oxysterol known to be formed in ozone- and singlet oxygen-mediated oxidations of
      cholesterol, has been detected in the atherosclerotic plaque and in the brain of
      patients suffering from Alzheimer's disease and Lewy body dementia. Previously,
      we have shown that, in H9c2 cardiomyoblasts, ChSeco induces oxidative stress
      followed by apoptosis involving both intrinsic and extrinsic signaling pathways.
      In the present study, we investigated the nature of reactive oxygen species (ROS)
      and its associated redox signaling in H9c2 cells upon treatment with ChSeco. Both
      catalase and deferoxamine, which lowered intracellular ROS, were found to
      alleviate the ChSeco-induced cytotoxicity. ChSeco-treated H9c2 cells showed a
      significant decrease in the intracellular catalase activity, suggesting the
      involvement of H(2)O(2) in the associated cytotoxicity. Additionally, in ChSeco
      exposed cells, there was a marked increase in lipid peroxidation and pre
      treatment with SB 203580 (p38 MAPK inhibitor) and MEK1/2 inhibitor (ERK1/2 and
      JNK inhibitor) rendered protection against the cytotoxicity. An early increase in
      the expression of p-SAPK/JNK or delayed p38 MAPK did not alter ATF-2 but
      decreased c-Jun expression in these cells. Overall, these findings are consistent
      with MAPK signaling resulting from increased cellular H(2)O(2) in ChSeco-induced
      cytotoxicity in cardiomyoblasts.

PMID- 21094129
TI  - Heme oxygenase-1 comes back to endoplasmic reticulum.
AB  - Originally identified as a rate-limiting enzyme for heme catabolism, heme
      oxygenase-1 (HO-1) has expanded its roles in anti-inflammation, anti-apoptosis
      and anti-proliferation for the last decade. Regulation of protein activity by
      location is well appreciated. Even though multiple compartmentalization of HO-1
      has been documented, the functional implication of this enzyme at these
      subcellular organelles is only partially elucidated. In this review we discuss
      the endoplasmic reticulum (ER)-residing HO-1 and its cytoprotective activity
      against ER stress.

PMID- 21094130
TI  - TEC protein tyrosine kinase is involved in the Erk signaling pathway induced by
      HGF.
AB  - BACKGROUND/AIMS: TEC, a member of the TEC family of non-receptor type protein
      tyrosine kinases, has recently been suggested to play a role in hepatocyte
      proliferation and liver regeneration. This study aims to investigate the putative
      mechanisms of TEC kinase regulation of hepatocyte differentiation, i.e. to
      explore which signaling pathway TEC is involved in, and how TEC is activated in
      hepatocyte after hepatectomy and hepatocyte growth factor (HGF) stimulation.
      METHODS: We performed immunoprecipitation (IP) and immunoblotting (IB) to examine
      TEC tyrosine phosphorylation after partial hepatectomy in mice and HGF
      stimulation in WB F-344 hepatic cells. The TEC kinase activity was determined by
      in vitro kinase assay. Reporter gene assay, antisense oligonucleotide and TEC
      dominant negative mutant (TEC(KM)) were used to examine the possible signaling
      pathways in which TEC is involved. The cell proliferation rate was evaluated by
      (3)H-TdR incorporation. RESULTS: TEC phosphorylation and kinase activity were
      increased in 1 h after hepatectomy or HGF treatment. TEC enhanced the activity of
      Elk and serum response element (SRE). Inhibition of MEK1 suppressed TEC
      phosphorylation. Blocking TEC activity dramatically decreased the activation of
      Erk. Reduced TEC kinase activity also suppressed the proliferation of WB F-344
      cells. These results suggest TEC is involved in the Ras-MAPK pathway and acts
      between MEK1 and Erk. CONCLUSIONS: TEC promotes hepatocyte proliferation and
      regeneration and is involved in HGF-induced Erk signaling pathway.

PMID- 21094131
TI  - Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated
      angiogenesis.
AB  - Heparan sulfate proteoglycans (HSPGs) are essential players in several steps of
      tumor-associated angiogenesis. As co-receptors for several pro-angiogenic factors
      such as VEGF and FGF, HSPGs regulate receptor-ligand interactions and play a
      vital role in signal transduction. Previously, we have employed an enzymatic
      strategy to show the importance of cell surface HSPGs in endothelial tube
      formation in vitro. We have recently found several fluoro-xylosides that can
      selectively inhibit proteoglycan synthesis in endothelial cells. The current
      study demonstrates that these fluoro-xylosides are effective inhibitors of
      endothelial tube formation in vitro using a matrigel based assay to simulate
      tumor-associated angiogenesis. These first generation scaffolds offer a promising
      stepping-stone to the discovery of more potent fluoro-xylosides that can
      effectively neutralize tumor growth.

PMID- 21094132
TI  - Galectin-3 binding protein promotes cell motility in colon cancer by stimulating
      the shedding of protein tyrosine phosphatase kappa by proprotein convertase 5.
AB  - It has previously been reported that shedding of the PTPkappa ectodomain drives
      enhanced motility of colon cancer cells. Herein, we provide mechanism underlying
      the regulation of PTPkappa shedding by galectin-3 binding protein. PTPkappa was
      inarguably scissored by the processed form of proprotein convertase 5
      (subtilisin/kexin type 5), and galectin-3 binding protein which is over-produced
      in colon cancer cells and tissues contributed to increased cancer cell motility
      by acting as a negative regulator of galectin-3 at the cell surface. The high
      expression ratio of galectin-3 binding protein to galectin-3 was clinically
      correlated to lymphatic invasion. These results suggest that galectin-3 binding
      protein may be a potential therapeutic target for treatment of, at least, colon
      cancer patients with high expression of galectin-3 binding protein.

PMID- 21094133
TI  - Transglutaminase 2 gene ablation protects against renal ischemic injury by
      blocking constant NF-kappaB activation.
AB  - Transglutaminase 2 knockout (TGase2(-/-)) mice show significantly reduced
      inflammation with decreased myofibroblasts in a unilateral ureteral obstruction
      (UUO) model, but the mechanism remains to be clarified. Nuclear factor-kappaB (NF
      kappaB) activation plays a major role in the progression of inflammation in an
      obstructive nephropathy model. However, the key factors extending the duration of
      NF-kappaB activation in UUO are not known. In several inflammatory diseases, we
      and others recently found that TGase 2 plays a key role in extending NF-kappaB
      activation, which contributes to the pathogenesis of disease. In the current
      study, we found that NF-kappaB activity in mouse embryogenic fibroblasts (MEFs)
      from TGase2(-/-) mice remained at the control level while the NF-kappaB activity
      of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the
      obstructive nephropathy model, we found that NF-kappaB activity remained at the
      control level in TGase2(-/-) mouse kidney tissues, as measured by COX-2
      expression, but was highly increased in WT tissues. We conclude that TGase 2 gene
      ablation reduces the duration of NF-kappaB activation in ischemic injury.

PMID- 21094134
TI  - Acetylation of EGF receptor contributes to tumor cell resistance to histone
      deacetylase inhibitors.
AB  - Alteration of epidermal growth factor receptor (EGFR) is involved in various
      human cancers and has been intensively investigated. A plethora of evidence
      demonstrates that posttranslational modifications of EGFR play a pivotal role in
      controlling its function and metabolism. Here, we show that EGFR can be
      acetylated by CREB binding protein (CBP) acetyltransferase. Interestingly, EGFR
      acetylation affects its tyrosine phosphorylation, which may contribute to cancer
      cell resistance to histone deacetylase inhibitors (HDACIs). Since there is an
      increasing interest in using HDACIs to treat various cancers in the clinic, our
      current study provides insights and rationale for selecting effective therapeutic
      regimen. Consistent with the previous reports, we also show that HDACI combined
      with EGFR inhibitors achieves better therapeutic outcomes and provides a
      molecular rationale for the enhanced effect of combination therapy. Our results
      unveil a critical role of EGFR acetylation that regulates EGFR function, which
      may have an important clinical implication.

PMID- 21094136
TI  - MyD88 is a mediator for the activation of Nrf2.
AB  - If not controlled properly, inflammatory response is often detrimental. However,
      in many cases, it can be self-limited and subsides without inflicting tissue
      damage. In this study, we tested the hypothesis that inflammatory stimuli can
      trigger anti-inflammatory response, which may contribute to limiting tissue
      damage induced by excessive inflammation. We found that treatment of bone marrow
      derived macrophages with lipopolysaccharide (LPS) activated NF-E2-related factor
      2 (Nrf2), a basic leucine zipper transcription factor that regulates
      inflammation, leading to expression of Nrf2-regulated genes including
      NAD(P)H:quinine oxidoreductase 1,glutamyl cysteine ligase catalytic unit and heme
      oxygenase-1. Suppression of Nrf2 by siRNA significantly diminished the expression
      of the Nrf2-regulated genes induced by LPS. By using pharmacological, genetic and
      epigenetic analyses, we found that activation of Nrf2 in response to LPS is
      dependent on MyD88 but independent of the production of reactive oxygen species.
      Together, our results show that activation of Nrf2 by MyD88 dependent signaling
      induced by LPS is an important intrinsic mechanism that limits excessive
      inflammation.

PMID- 21094137
TI  - Characterization of green mutants in Fremyella diplosiphon provides insight into
      the impact of phycoerythrin deficiency and linker function on complementary
      chromatic adaptation.
AB  - Functions of phycobiliprotein (PBP) linkers are less well studied than other PBP
      polypeptides that are structural components or required for the synthesis of the
      light-harvesting phycobilisome (PBS) complexes. Linkers serve both structural and
      functional roles in PBSs. Here, we report the isolation of a phycoerythrin (PE)
      rod-linker mutant and a novel PE-deficient mutant in Fremyella diplosiphon. We
      describe their phenotypic characterization, including light-dependent
      photosynthetic pigment accumulation and photoregulation of cellular morphology.
      PE-linker protein CpeE and a novel protein impact PE accumulation, and thus PBS
      function, primarily under green light conditions.

PMID- 21094135
TI  - Differential expression and localization of 12/15 lipoxygenases in adipose tissue
      in human obese subjects.
AB  - Adipose tissue inflammation in obesity is a major factor leading to
      cardiovascular disease and type 2 diabetes.12/15 lipoxygenases (ALOX) play an
      important role in the generation of inflammatory mediators, insulin resistance
      and downstream immune activation in animal models of obesity. However, the
      expression and roles of 12/15ALOX isoforms, and their cellular sources in human
      subcutaneous (sc) and omental (om) fat in obesity is unknown. The objective of
      this study was to examine the gene expression and localization of ALOX isoforms
      and relevant downstream cytokines in subcutaneous (sc) and omental (om) adipose
      tissue in obese humans. Paired biopsies of sc and om fat were obtained during
      bariatric surgeries from 24 morbidly obese patients. Gene and protein expression
      for ALOX15a, ALOX15b and ALOX 12 were measured by real-time PCR and western
      blotting in adipocytes and stromal vascular fractions (SVF) from om and sc
      adipose tissue along with the mRNA expression of the downstream cytokines IL-12a,
      IL-12b, IL-6, IFNgamma and the chemokine CXCL10. In a paired analysis, all ALOX
      isoforms, IL-6, IL-12a and CXCL10 were significantly higher in om vs. sc fat.
      ALOX15a mRNA and protein expression was found exclusively in om fat. All of the
      ALOX isoforms were expressed solely in the SVF. Further fractionation of the SVF
      in CD34+ and CD34- cells indicated that ALOX15a is predominantly expressed in the
      CD34+ fraction including vascular and progenitor cells, while ALOX15B is mostly
      expressed in the CD34- cells containing various leucocytes and myeloid cells.
      This result was confirmed by immunohistochemistry showing exclusive localization
      of ALOX15a in the om fat and predominantly in the vasculature and non-adipocyte
      cells. Our finding is identifying selective expression of ALOX15a in human om but
      not sc fat. This is a study showing a major inflammatory gene exclusively
      expressed in visceral fat in humans.

PMID- 21094138
TI  - Centchroman inhibits proliferation of head and neck cancer cells through the
      modulation of PI3K/mTOR pathway.
AB  - Centchroman (CC; 67/20; INN: Ormeloxifene) is a non-steroidal antiestrogen
      extensively used as a female contraceptive in India. In the present study, we
      report the anti-proliferative effect of CC in head and neck squamous cell
      carcinoma (HNSCC) cells. CC inhibited cell proliferation in a dose dependent
      manner at 24 h of treatment. Further studies showed that CC treatment induced
      apoptosis, inhibited Akt/mTOR and signal transducers and activators of
      transcription protein 3 (STAT3) signaling, altered proteins associated with cell
      cycle regulation and DNA damage and inhibited colony forming efficiency of HNSCC
      cells. In addition, CC displayed anti-proliferative activity against a variety of
      non-HNSCC cell lines of diverse origin. The ability of CC to serve as a dual
      inhibitor of Akt/mTOR and STAT3 signaling warrants further studies into its role
      as a therapeutic strategy against HNSCC.

PMID- 21094139
TI  - Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human
      cholangiocellular carcinoma cells.
AB  - Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by
      Streptococcus intermedius, which is associated with human brain and liver
      abscesses. Although intrahepatic bile duct cells play a valuable role in the
      pathogenesis of liver abscess, the molecular mechanism of ILY-treated
      intrahepatic bile duct cells remains unknown. In this study, we report that ILY
      induced a nuclear accumulation of intracellular calcium ([Ca(2+)]i) in human
      cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced
      NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In
      contrast to the result that ILY induced NF-kappaB translocation in human hepatic
      HepG2 cells, ILY did not affect NF-kappaB localization in HuCCT1 cells.
      Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented
      by [Ca(2+)]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine
      A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it
      was inhibited by the pre-treatment with cyclosporine A, indicating that the
      calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY
      induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be
      related to the pathogenesis of S. intermedius in human bile duct cells.

PMID- 21094140
TI  - 1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK
      knock-out mice.
AB  - AHNAK is a giant protein of approximately 700 kDa identified in human
      neuroblastomas and skin epithelial cells. Recently, we found that AHNAK knock-out
      (AHNAK(-/-)) mice have a strong resistance to high-fat diet-induced obesity. In
      this study, we applied (1)H NMR-based metabolomics with multivariate statistical
      analysis to compare the altered metabolic patterns detected in urine from high
      fat diet (HFD) fed wild-type and AHNAK(-/-) mice and investigate the mechanisms
      underlying the resistance to high-fat diet-induced obesity in AHNAK(-/-) mice. In
      global profiling, principal components analysis showed a clear separation between
      the chow diet and HFD groups; wild-type and AHNAK(-/-) mice were more distinctly
      separated in the HFD group compared to the chow diet group. Based on target
      profiling, the urinary metabolites of HFD-fed AHNAK(-/-) mice gave higher levels
      of methionine, putrescine, tartrate, urocanate, sucrose, glucose, threonine, and
      3-hydroxyisovalerate. Furthermore, two-way ANOVAs indicated that diet type,
      genetic type, and their interaction (gene * diet) affect the metabolite changes
      differently. Most metabolites were affected by diet type, and putrescine,
      threonine, urocanate, and tartrate were also affected by genetic type. In
      addition, cis-aconitate, succinate, glycine, histidine, methylamine (MA),
      phenylacetylglycine (PAG), methionine, putrescine, uroconate, and tartrate showed
      interaction effects. Through the pattern changes in urinary metabolites of HFD
      fed AHNAK(-/-) mice, our data suggest that the strong resistance to HFD-induced
      obesity in AHNAK(-/-) mice comes from perturbations of amino acids, such as
      methionine, putrescine, threonine, and histidine, which are related to fat
      metabolism. The changes in metabolites affected by microflora such as PAG and MA
      were also observed. In addition, resistance to obesity in HFD-fed AHNAK(-/-) mice
      was not related to an activated tricarboxylic acid cycle. These findings
      demonstrate that (1)H NMR-based metabolic profiling of urine is suitable for
      elucidating possible biological pathways perturbed by functional loss of AHNAK on
      HFD feeding and could elucidate the mechanism underlying the resistance to high
      fat diet-induced obesity in AHNAK(-/-) mice.

PMID- 21094141
TI  - N-terminal segment of proinsulin C-peptide active in insulin
      interaction/desaggregation.
AB  - Evidence has emerged that proinsulin C-peptide has at least three types of
      functional interactions in addition to its role during synthesis and secretion of
      insulin. Thus, C-peptide has been shown (i) to bind to cell membranes triggering
      G-protein-mediated intracellular signaling; (ii) to be internalized into cells
      and nuclei promoting transcription of rRNA and expression of particular genes;
      and (iii) to interact with peptides, including insulin, causing desaggregation of
      insulin oligomers like a chaperone, and with itself, causing homo-oligomers
      potentially capable of forming aggregates and deposits. In this work, we studied
      the insulin-C-peptide interactions by monitoring desaggregation and binding
      effects of C-peptide fragments on insulin. We find that the N-terminal segment of
      C-peptide harbors an interaction with insulin and that Glu11 appears to play a
      role in this action. We conclude that C-peptide fragments with this residue can
      mimic C-peptide in biophysical interactions with insulin, and that the insulin
      interacting and membrane-interacting effects of C-peptide are distinct,
      ascribable to separate C-peptide segments, N- and C-terminally, respectively. The
      findings may have relevance to peptide effects in diabetic and healthy states.

PMID- 21094142
TI  - Mechanism of protein splicing of the Pyrococcus abyssi lon protease intein.
AB  - Protein splicing is a post-translational process by which an intervening
      polypeptide, the intein, excises itself from the flanking polypeptides, the
      exteins, coupled to ligation of the exteins. The lon protease of Pyrococcus
      abyssi (Pab) is interrupted by an intein. When over-expressed as a fusion protein
      in Escherichia coli, the Pab lon protease intein can promote efficient protein
      splicing. Mutations that block individual steps of splicing generally do not lead
      to unproductive side reactions, suggesting that the intein tightly coordinates
      the splicing process. The intein can splice, although it has Lys in place of the
      highly conserved penultimate His, and mutants of the intein in the C-terminal
      region lead to the accumulation of stable branched-ester intermediate.

PMID- 21094143
TI  - Dual effect of hypochlorite in the modification of high density lipoproteins.
AB  - HDL-cholesterol levels are inversely correlated to the risk of cardiovascular
      disease. In recent years the concept that not only the quantity, but also the
      quality of HDL is related to their atheroprotective function has gained momentum.
      In fact several studies have showed that HDL can shift their properties from anti
      atherogenic to pro-atherogenic upon chemical or enzymatic "modification".
      However, not all kind of modifications affect the antiatherogenic properties of
      HDL. For example, tyrosylation of HDL improves its ability to remove cholesterol
      from cultured cells and inhibits mice atherosclerotic lesion formation; oxidation
      of HDL(3) with 15-lipoxygenase or with copper ions for short time induce the
      formation of pre-beta-migrating particles that are highly effective as
      cholesterol acceptors from lipid laden cells. Myeloperoxidase modifies HDL and
      apoA-I and reduces their ability to promote ABCA1-mediated cholesterol efflux. In
      the present study we show that modification with low concentration HOCl (a
      myeloperoxidase product) induces the formation of pre-beta-migrating particles,
      thus improving the function of HDL in the reverse cholesterol transport, without
      affecting the anti-inflammatory activity. At higher HOCl concentration, pre-beta
      migrating particles were not detectable and the anti-inflammatory properties of
      HDL were lost. These findings suggest that during early phases of inflammation,
      when a low HOCl concentration is generated, changes in HDL occur that increase
      their ability to remove cholesterol and sparing anti-inflammatory properties;
      later during acute inflammation, when higher HOCl concentration are present
      changes in HDL occur that severely decrease their ability to remove cholesterol
      from macrophages and to protect endothelial cells from pro-inflammatory stimuli.

PMID- 21094144
TI  - Protection against dexamethasone-induced muscle atrophy is related to modulation
      by testosterone of FOXO1 and PGC-1alpha.
AB  - Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and
      reduced protein synthesis, associated with increased expression of two muscle
      specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein
      synthesis, REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the
      transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC
      1alpha has been shown to attenuate many forms of muscle atrophy and to repress
      FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced
      muscle atrophy can be prevented by testosterone, which blocks up-regulation by
      dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle
      atrophy was used to further characterize effects of testosterone to abrogate
      adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to
      determine how these agents affect PGC-1alpha, and its upstream activators, p38
      MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the
      dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and
      nuclear protein. Dexamethasone reduced total and nuclear PGC-1alpha protein
      levels in the gastrocnemius; co-administration of testosterone with dexamethasone
      increased total and nuclear PGC-1alpha levels above those present in untreated
      controls. Testosterone blocked dexamethasone-induced decreases in activity of p38
      MAPK in the gastrocnemius muscle. Regulation of FOXO1, PGC-1alpha and p38 MAPK by
      testosterone may represent a novel mechanism by which this agent protects against
      dexamethasone-induced muscle atrophy.

PMID- 21094145
TI  - Hypoxic remodelling of Ca2+ stores does not alter human cardiac myofibroblast
      invasion.
AB  - Cardiac fibroblasts are the most abundant cell type in the heart, and play a key
      role in the maintenance and repair of the myocardium following damage such as
      myocardial infarction by transforming into a cardiac myofibroblast (CMF)
      phenotype. Repair occurs through controlled proliferation and migration, which
      are Ca(2+) dependent processes, and often requires the cells to operate within a
      hypoxic environment. Angiotensin converting enzyme (ACE) inhibitors reduce
      infarct size through the promotion of bradykinin (BK) stability. Although CMF
      express BK receptors, their activity under the reduced O(2) conditions that occur
      following infarct are entirely unexplored. Using Fura-2 microfluorimetry on
      primary human CMF, we found that hypoxia significantly increased the mobilisation
      of Ca(2+) from intracellular stores in response to BK whilst capacitative Ca(2+)
      entry (CCE) remained unchanged. The enhanced store mobilisation was due to a
      striking increase in CMF intracellular Ca(2+)-store content under hypoxic
      conditions. However, BK-induced CMF migration or proliferation was not affected
      following hypoxic exposure, suggesting that Ca(2+) influx rather than
      mobilisation is of primary importance in CMF migration and proliferation.

PMID- 21094146
TI  - Steroid synthesis by primary human keratinocytes; implications for skin disease.
AB  - Cortisol-based therapy is one of the most potent anti-inflammatory treatments
      available for skin conditions including psoriasis and atopic dermatitis. Previous
      studies have investigated the steroidogenic capabilities of keratinocytes, though
      none have demonstrated that these skin cells, which form up to 90% of the
      epidermis are able to synthesise cortisol. Here we demonstrate that primary human
      keratinocytes (PHK) express all the elements required for cortisol
      steroidogenesis and metabolise pregnenolone through each intermediate steroid to
      cortisol. We show that normal epidermis and cultured PHK express each of the
      enzymes (CYP11A1, CYP17A1, 3betaHSD1, CYP21 and CYP11B1) that are required for
      cortisol synthesis. These enzymes were shown to be metabolically active for
      cortisol synthesis since radiometric conversion assays traced the metabolism of
      [7-(3)H]-pregnenolone through each steroid intermediate to [7-(3)H]-cortisol in
      cultured PHK. Trilostane (a 3betaHSD1 inhibitor) and ketoconazole (a CYP17A1
      inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally,
      we show that normal skin expresses two cholesterol transporters, steroidogenic
      acute regulatory protein (StAR), regarded as the rate-determining protein for
      steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been
      linked to cholesterol transport in steroidogenesis. The expression of StAR and
      MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that
      are commonly treated with cortisol, suggesting dysregulation of epidermal steroid
      synthesis in these patients. Collectively these data show that PHK are capable of
      extra-adrenal cortisol synthesis, which could be a fundamental pathway in skin
      biology with implications in psoriasis and atopic dermatitis.

PMID- 21094148
TI  - Reversible inactivation of bovine plasma amine oxidase by cysteamine and related
      analogs.
AB  - Cysteamine (1) was reported many years ago to reversibly inhibit lentil seedling
      amine oxidase, through the formation of a complex with thioacetaldehyde, the
      turnover product of 1. Herein, cysteamine (1) and its analogs 2
      (methylamino)ethanethiol (3) and 3-aminopropanethiol (6) were found to be
      reversible inhibitors of bovine plasma amine oxidase (BPAO), but 2
      (methylthio)ethylamine (7) was determined to be a weak irreversible inhibitor of
      BPAO. Based on our results, indicating the necessity of a sulfhydryl-amine for
      reversible inactivation of BPAO, the failure of inhibited BPAO to recover
      activity after gel filtration, the first-order kinetics of activity recovery upon
      dialysis, and 2,4,6-trihydroxyphenylalanine quinine (TPQ) cofactor transformation
      which indicated from the results of phenylhydrazine titration and substrate
      protection, we propose a mechanism for the reversible inactivation of BPAO by 1
      involving the formation of a cofactor adduct, thiazolidine, between BPAO and 1.

PMID- 21094147
TI  - Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2
      reduction.
AB  - Abnormal lung inflammation and oxidant burden are associated with a significant
      reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We
      hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to
      inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid
      resistance in attenuating lung inflammatory response, which may be due to
      oxidant/antioxidant imbalance. Loss of antioxidant transcription factor Nrf2
      resulted in decreased HDAC2 level in lung, and increased inflammatory lung
      response which was not reversed by steroid. Thus, steroid resistance or inability
      of steroids to control lung inflammatory response is dependent on Nrf2-HDAC2
      axis. These findings have implications in steroid resistance, particularly during
      the conditions of oxidative stress when the lungs are more susceptible to
      inflammatory response, which is seen in patients with chronic obstructive
      pulmonary disease, asthma, rheumatoid arthritis, and inflammatory bowel disease.

PMID- 21094149
TI  - Engineered mutated glutaredoxins mimicking peculiar plant class III glutaredoxins
      bind iron-sulfur centers and possess reductase activity.
AB  - In order to gather biochemical information about class III glutaredoxins (CCxC/S
      active sites), the active sites of two poplar class I glutaredoxins, GrxC1 and
      C4, CGYC and CPYC, respectively, were transformed into CCMC or CCMS. All the
      recombinant mutated proteins bind [2Fe-2S] centers into holodimers, whereas
      monomeric apoforms possess glutathione-dependent reductase activity. The
      functionally important, hydrophobic GALWL C-terminal end, found in most class III
      glutaredoxins, prevents expression in Escherichia coli. Changing the C-terminal
      end of GrxS7.2, a genuine class III glutaredoxin, allowed purifying some
      holoproteins. These properties are discussed considering the documented function
      of class III glutaredoxins in development.

PMID- 21094150
TI  - Gene expression of serotonin and dopamine receptors and monoamine oxidase-A in
      the brain of dominant and subordinate pubertal domestic pigs (Sus scrofa) fed a
      beta-adrenoreceptor agonist.
AB  - Aggression is a major source of social stress with negative effects on health and
      well-being, yet limited information is known about the molecular mechanisms
      mediating aggressive behavior in swine. Ractopamine (RAC) is a beta
      adrenoreceptor agonist that enhances growth but increases aggressive behaviors in
      female pigs. Thus, the effects of RAC, sex, and social rank on the mRNA abundance
      of genes encoding serotonin and dopamine receptors, and monoamine oxidase (MAO)-A
      in brains of sub-adult pigs were evaluated. Top dominant and bottom subordinate
      pigs (16/sex) in pens of 4 pigs were determined, and fed either the control or
      RAC diets. At day 31, their raphe nuclei (RN), amygdala (AMY), frontal cortex
      (FC), and hypothalamus (HYP) were dissected; relative mRNA abundance for 5
      HT1(B), 5-HT2(A), 5-HT2(B), and D1 receptors, and MAO-A was determined by Q-RT
      PCR and data subjected to multivariate linear mixed model analysis and Tukey post
      hoc test. Expression of 5-HT1(B) and MAO-A was suppressed in the AMY of female
      pigs; 5-HT2(B) expression was also suppressed in the RN, FC and HYP of females
      and RN of dominant pigs (P < 0.05). Expression of 5-HT2(A) was more up-regulated
      in RN of females compared to males (P < 0.05). Expression of D1 varied in RN and
      FC mostly as a function of RAC feeding and its interaction with sex and social
      rank (P < 0.05). While RAC feeding is related to changes in expression of the D1
      receptor mRNA, suppression in expression of serotonergic genes detected in the
      brain of pigs, especially in females independent of social rank, may be mediating
      the inter-individual offensive aggression.

PMID- 21094151
TI  - Cytokinetics of adult rat SVZ after EAE.
AB  - Cytokinetics regulating cell cycle division can be modulated by several
      endogenous factors. EAE (experimental autoimmune encephalomyelitis) increases
      proliferation of progenitor cells in the subventricular zone (SVZ). Using
      cumulative and single S phase labeling with 5-bromo-2-deoxyuridine, we examined
      cell cycle kinetics of neural progenitor cells in the SVZ after EAE. 20% of the
      SVZ cell population was proliferating in adjuvant control rats. However, EAE
      significantly increased them up to 27% and these cells had a cell cycle length
      (TC) of 15.6h, significantly (P<0.05) shorter than the 19 h TC in non EAE SVZ
      cells. Few TUNEL (+) cells were detected in the SVZ cells of adjuvant controls.
      EAE increased (P<0.05) TUNEL (+) nuclei in SVZ suggesting early stage progenitor
      cell death. Cell cycle phase analysis revealed that EAE substantially shortened
      the length of the G1 phase (9.6h) compared with the G1 phase of 12.25 h in
      adjuvant control SVZ cells (P<0.05). This reduction in G1 contributes to EAE
      induced reduction of TC because no significant changes were detected on the
      length of S, G2 and M phases between the two groups. Our results show a surge in
      proliferating progenitor cells in the SVZ with concomitant increase in apoptotic
      cell death after EAE. Furthermore, increase in the SVZ proliferation contributes
      to EAE-induced neurogenesis and this increase is regulated by shortening the G1
      phase. Our investigation suggests the activation of quiescent cells in SVZ to
      generate actively proliferating progenitors. Moreover, the increase in the cell
      death in proliferating population may contribute towards negative regulation of
      proliferative cell number and hence diminished regenerative capacity of CNS
      following EAE.

PMID- 21094153
TI  - Studies on the effects of heparin products on pregnancy-associated plasma protein
      A.
AB  - BACKGROUND: Intravenous low molecular weight (LMWH) and unfractionated heparin
      (UFH) increase the circulating concentrations of pregnancy-associated plasma
      protein A (PAPP-A), a novel cardiac risk marker, in haemodialysis and coronary
      angiography patients. METHODS: To further investigate the mechanisms of heparin
      effects, free PAPP-A was analysed in serial serum samples collected during
      haemodialysis (intravenous LMWH), carotid endarterectomy or abdominal aortic
      aneurysm surgery (intravenous UFH), treatment at intensive care unit
      (subcutaneous LMWH), and coronary angiography (intravenous bivalirudin). PAPP-A
      was extracted from plaque tissue samples of endarterectomy and aneurysm patients.
      The interaction between heparin products and free PAPP-A was studied with gel
      filtration. RESULTS: After intravenous UFH and LMWH free PAPP-A increased
      significantly but bivalirudin had no effect. After LMWH bolus in haemodialysis
      patients 85% of free PAPP-A was cleared with a half-life of 13.1 min and the rest
      with a half-life of 96.6 min. Subcutaneous LMWH led to lower and slower free PAPP
      A elevation. PAPP-A extracted from plaque tissues was in free form and extraction
      was strongly enhanced by LMWH. Heparin products increased the molecular size of
      free PAPP-A. CONCLUSIONS: The heparin-induced PAPP-A elevation is seen in various
      patients and should be taken into account when PAPP-A is studied as a biomarker.

PMID- 21094152
TI  - Realgar- and cinnabar-containing an-gong-niu-huang wan (AGNH) is much less
      acutely toxic than sodium arsenite and mercuric chloride.
AB  - An-gong-niu-huang wan (AGNH) is a famous traditional Chinese medicine used for
      brain trauma, hemorrhage, and coma. AGNH contains 10% realgar (As4S4) and 10%
      cinnabar (HgS). Both As and Hg are well-known for their toxic effects, and the
      safety of AGNH is of concern. To address this question, the acute toxicity of
      AGNH, realgar and cinnabar were compared to sodium arsenite (NaAsO2) and mercuric
      chloride (HgCl2). Mice were administrated orally AGNH at 1, 3 and 6g/kg. AGNH at
      3g/kg contains 2.8mmol As/kg as realgar and 1.18mmol Hg/kg as cinnabar. Realgar,
      cinnabar, arsenite (0.28 mmol/kg, 10% of realgar) and HgCl2 (0.256 mmol/kg, 20%
      of cinnabar) were orally given to mice for comparison. Blood and tissues were
      collected 8h later for toxicity evaluation. Serum alanine aminotransferase was
      increased by arsenite and blood urea nitrogen was increased by HgCl2. Total As
      accumulation after arsenite in liver (100-fold) and kidney (13-fold) was much
      higher than that after realgar. The accumulation of Hg after HgCl2 in liver was
      400-fold higher and kidney 30-fold higher than after cinnabar. Histopathology
      showed moderate liver and kidney injuries after arsenite and HgCl2, but injuries
      were mild or absent after AGNH, realgar, and cinnabar. The expression of
      metallothionein-1, a biomarker of metal exposure, was increased 4-10-fold by
      arsenite and HgCl2, but was unchanged by AGNH, realgar and cinnabar. Thus, AGNH,
      realgar and cinnabar are much less toxic acutely than arsenite and HgCl2. The
      chemical forms of As and Hg are extremely important factors in determining their
      disposition and toxicity.

PMID- 21094154
TI  - A comparison of restriction fragment length polymorphism, tetra primer
      amplification refractory mutation system PCR and unlabeled probe melting analysis
      for LTA+252 C>T SNP genotyping.
AB  - BACKGROUND: From the wide range of methods currently available for genotyping, we
      wished to identify a quick, reliable and affordable approach for routine use in
      our laboratory for LTA+252 C>T SNP screening. METHODS: We set up and compared
      three genotyping methods for SNP detection: restriction fragment length
      polymorphism (RFLP), tetra primer amplification refractory mutation system PCR
      (TPAP) and unlabeled probe melting analysis (UPMA). The SNP model used was
      LTA+252 C>T, a cytokine gene polymorphism that has been associated with response
      to treatment in rheumatoid arthritis. The study was performed using 46 samples
      from healthy Caucasian volunteers. RESULTS: Allele and genotype distribution was
      similar to that previously described in the same population. All three genotyping
      methods showed good reproducibility and are suitable for a medium scale
      throughput molecular platform. UPMA was the most cost effective, reliable and
      safe method since it required the shortest technician time, could be performed in
      a single closed tube and involved automatic data analysis. CONCLUSION: This work
      is the first to compare these three genotyping techniques and provides evidence
      for UPMA being the method of choice for LTA+252 C>T SNP genotyping.

PMID- 21094156
TI  - A novel zinc-carboxypeptidase SURO-1 regulates cuticle formation and body
      morphogenesis in Caenorhabditis elegans.
AB  - Cuticle formation and molting are critical for the development of Caenorhabditis
      elegans. To understand cuticle formation more clearly, we screened for
      suppressors in transgenic worms that expressed dominant ROL-6 collagen proteins.
      The suro-1 mutant, which is mild dumpy, exhibited a different ROL-6::GFP
      localization pattern compared to other Dpy mutants. We identified mutations in
      three suro-1 mutants, and found that suro-1 (ORF R11A5.7) encodes a putative zinc
      carboxypeptidase homologue. The expression of this enzyme in the hypodermis and
      the genetic interactions between this enzyme and other collagen-modifying enzyme
      mutants suggest a regulatory role in collagen processing and cuticle organization
      for this novel carboxypeptidase. These findings aid our understanding of cuticle
      formation during worm development.

PMID- 21094155
TI  - The mouse KRAB zinc-finger protein CHATO is required in embryonic-derived tissues
      to control yolk sac and placenta morphogenesis.
AB  - Yolk sac and placenta are required to sustain embryonic development in mammals,
      yet our understanding of the genes and processes that control morphogenesis of
      these extraembryonic tissues is still limited. The chato mutation disrupts
      ZFP568, a Kruppel-Associated-Box (KRAB) domain Zinc finger protein, and causes a
      unique set of extraembryonic malformations, including ruffling of the yolk sac
      membrane, defective extraembryonic mesoderm morphogenesis and vasculogenesis,
      failure to close the ectoplacental cavity, and incomplete placental development.
      Phenotypic analysis of chato embryos indicated that ZFP568 does not control
      proliferation or differentiation of extraembryonic lineages but rather regulates
      the morphogenetic events that shape extraembryonic tissues. Analysis of chimeric
      embryos showed that Zfp568 function is required in embryonic-derived lineages,
      including the extraembryonic mesoderm. Depleting Zfp568 affects the ability of
      extraembryonic mesoderm cells to migrate. However, explanted Zfp568 mutant cells
      could migrate properly when plated on appropriate extracellular matrix
      conditions. We show that expression of Fibronectin and Indian Hedgehog are
      reduced in chato mutant yolk sacs. These data suggest that ZFP568 controls the
      production of secreted factors required to promote morphogenesis of
      extraembryonic tissues. Our results support previously undescribed roles of the
      extraembryonic mesoderm in yolk sac morphogenesis and in the closure of the
      ectoplacental cavity and identify a novel role of ZFP568 in the development of
      extraembryonic tissues.

PMID- 21094157
TI  - 14-3-3 proteins fine-tune plant nutrient metabolism.
AB  - 14-3-3 Proteins regulate many cellular processes by binding to phosphorylated
      proteins. Previous findings suggest a connection between three 14-3-3 isoforms
      and plant nutrient signaling. To better understand how these 14-3-3s regulate
      metabolism in response to changes in plant nutrient status, putative new targets
      involved in nitrogen (N) and sulfur (S) metabolisms have been identified. The
      interactions between these 14-3-3s and multiple proteins involved in N and S
      metabolism and altered activity of the target proteins were confirmed in planta.
      Using a combination of methods, this work elucidates how 14-3-3s function as
      modulators of plant N and S metabolic pathways.

PMID- 21094158
TI  - Synthetic lethality: general principles, utility and detection using genetic
      screens in human cells.
AB  - Synthetic lethality occurs when the simultaneous perturbation of two genes
      results in cellular or organismal death. Synthetic lethality also occurs between
      genes and small molecules, and can be used to elucidate the mechanism of action
      of drugs. This area has recently attracted attention because of the prospect of a
      new generation of anti-cancer drugs. Based on studies ranging from yeast to human
      cells, this review provides an overview of the general principles that underlie
      synthetic lethality and relates them to its utility for identifying gene
      function, drug action and cancer therapy. It also identifies the latest
      strategies for the large-scale mapping of synthetic lethalities in human cells
      which bring us closer to the generation of comprehensive human genetic
      interaction maps.

PMID- 21094159
TI  - Flexibility in the PP1:spinophilin holoenzyme.
AB  - Protein phosphatase 1 (PP1) interacts with ~200 regulatory proteins to form
      holoenzymes, which target PP1 to specific locations and regulate its specificity.
      While it is known that many PP1 regulatory proteins are dynamic in the unbound
      state, much less is known about the residual flexibility after PP1 holoenzyme
      formation. Here, we have used small angle X-ray scattering to investigate the
      flexibility of the PP1:spinophilin holoenzyme in solution. Collectively, our data
      shows that the PP1:spinophilin holoenzyme is dynamic in solution, which allows
      for an increased capture radius of spinophilin and is likely important for its
      biological role.

PMID- 21094160
TI  - Association of TP53 mutations with stem cell-like gene expression and survival of
      patients with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Mutations in TP53, a tumor suppressor gene, are associated
      with prognosis of many cancers. However, the prognostic values of TP53 mutation
      sites are not known for patients with hepatocellular carcinoma (HCC) because of
      heterogeneity in their geographic and etiologic backgrounds. METHODS: TP53
      mutations were investigated in a total of 409 HCC patients, including Chinese (n
      = 336) and white (n = 73) patients, using the direct sequencing method. RESULTS:
      A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%).
      HCC patients with TP53 mutations had a shorter overall survival time compared
      with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence
      interval [CI]: 1.37-2.52; P < .001). The hot spot mutations R249S and V157F were
      significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI:
      1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29-2.51; P <
      .001). Gene expression analysis revealed the existence of stem cell-like traits
      in tumors with TP53 mutations. These findings were validated in breast and lung
      tumor samples with TP53 mutations. CONCLUSIONS: TP53 mutations, particularly the
      hot spot mutations R249S and V157F, are associated with poor prognosis for
      patients with HCC. The acquisition of stem cell-like gene expression traits might
      contribute to the aggressive behavior of tumors with TP53 mutation.

PMID- 21094161
TI  - The RelA nuclear localization signal folds upon binding to IkappaBalpha.
AB  - The nuclear localization signal (NLS) polypeptide of RelA, the canonical nuclear
      factor-kappaB family member, is responsible for regulating the nuclear
      localization of RelA-containing nuclear factor-kappaB dimers. The RelA NLS
      polypeptide also plays a crucial role in mediating the high affinity and
      specificity of the interaction of RelA-containing dimers with the inhibitor
      IkappaBalpha, forming two helical motifs according to the published X-ray crystal
      structure. In order to define the nature of the interaction between the RelA NLS
      and IkappaBalpha under solution conditions, we conducted NMR and isothermal
      titration calorimetry studies using a truncated form of IkappaBalpha containing
      residues 67-206 and a peptide spanning residues 293-321 of RelA. The NLS peptide,
      although largely unfolded, has a weak tendency toward helical structure when free
      in solution. Upon addition of the labeled peptide to unlabeled IkappaBalpha, the
      resonance dispersion in the NMR spectrum is significantly greater, providing
      definitive evidence that the RelA NLS polypeptide folds upon binding
      IkappaBalpha. Isothermal titration calorimetry studies of single-point mutants
      reveal that residue F309, which is located in the middle of the more C-terminal
      of the two helices (helix 4) in the IkappaBalpha-bound RelA NLS polypeptide, is
      critical for the binding of the RelA NLS polypeptide to IkappaBalpha. These
      results help to explain the role of helix 4 in mediating the high affinity of
      RelA for IkappaBalpha.

PMID- 21094162
TI  - Creating designed zinc-finger nucleases with minimal cytotoxicity.
AB  - Zinc-finger nucleases (ZFNs) have emerged as powerful tools for delivering a
      targeted genomic double-strand break (DSB) to either stimulate local homologous
      recombination with investigator-provided donor DNA or induce gene mutations at
      the site of cleavage in the absence of a donor by nonhomologous end joining both
      in plant cells and in mammalian cells, including human cells. ZFNs are formed by
      fusing zinc-finger proteins to the nonspecific cleavage domain of the FokI
      restriction enzyme. ZFN-mediated gene targeting yields high gene modification
      efficiencies (>10%) in a variety of cells and cell types by delivering a
      recombinogenic DSB to the targeted chromosomal locus, using two designed ZFNs.
      The mechanism of DSB by ZFNs requires (1) two ZFN monomers to bind to their
      adjacent cognate sites on DNA and (2) the FokI nuclease domains to dimerize to
      form the active catalytic center for the induction of the DSB. In the case of
      ZFNs fused to wild-type FokI cleavage domains, homodimers may also form; this
      could limit the efficacy and safety of ZFNs by inducing off-target cleavage. In
      this article, we report further refinements to obligate heterodimer variants of
      the FokI cleavage domain for the creation of custom ZFNs with minimal cellular
      toxicity. The efficacy and efficiency of the reengineered obligate heterodimer
      variants of the FokI cleavage domain were tested using the green fluorescent
      protein gene targeting reporter system. The three-finger and four-finger zinc
      finger protein fusions to the REL_DKK pair among the newly generated FokI
      nuclease domain variants appear to eliminate or greatly reduce the toxicity of
      designer ZFNs to human cells.

PMID- 21094163
TI  - Analysis of disease-linked rhodopsin mutations based on structure, function, and
      protein stability calculations.
AB  - Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited diseases
      that result in progressive retinal degeneration, characterized by visual field
      constriction and night blindness. A total of 103 mutations in rhodopsin are
      linked to RP to date, and the phenotypes range from severe to asymptomatic. To
      study the relation between phenotype and rhodopsin stability in disease mutants,
      we used a structure-based approach. For 12 of the mutants located at the protein
      lipid interphase, we used the von Heijne water-membrane transfer scale, and we
      find that 9 of the mutations could affect membrane insertion. For 91 mutants, we
      used the protein design algorithm FoldX. The 3 asymptomatic mutations had no
      significant reduced stability, 2 were unsuitable for FoldX analysis since the
      structure was incorrect in this region, 63 mutations had a significant change in
      protein stability (>1.6 kcal/mol), and 23 mutations had energy change values
      under the prediction error threshold (<1.6 kcal/mol). Out of these 23, the
      disease-causing effect could be explained by the involvement in other functions
      (e.g., glycosylation motifs, the interface with arrestin and transducin, and the
      cilia-binding motif) for 19 mutants. The remaining 4 mutants were probably
      incorrectly associated with RP or have functionalities not discovered yet. For
      destabilizing mutations where clinical data were available, we found a highly
      significant correlation between FoldX energy changes and the average age of night
      blindness and between FoldX energy changes and daytime vision loss onset. Our
      detailed structural, functional, and energetic analysis provides a complete
      picture of the rhodopsin mutations and can guide mutation-specific therapies.

PMID- 21094164
TI  - Probing water accessibility in HET-s(218-289) amyloid fibrils by solid-state NMR.
AB  - Despite the importance of protein fibrils in the context of conformational
      diseases, information on their structure is still sparse. Hydrogen/deuterium
      exchange measurements of backbone amide protons allow the identification hydrogen
      bonding patterns and reveal pertinent information on the amyloid beta-sheet
      architecture. However, they provide only little information on the identity of
      residues exposed to solvent or buried inside the fibril core. NMR spectroscopy is
      a potent method for identifying solvent-accessible residues in proteins via
      observation of polarization transfer between chemically exchanging side-chain
      protons and water protons. We show here that the combined use of highly
      deuterated samples and fast magic-angle spinning greatly attenuates unwanted spin
      diffusion and allows identification of polarization exchange with the solvent in
      a site-specific manner. We apply this measurement protocol to HET-s(218-289)
      prion fibrils under different conditions (including physiological pH, where
      protofibrils assemble together into thicker fibrils) and demonstrate that each
      protofibril of HET-s(218-289), is surrounded by water, thus excluding the
      existence of extended dry interfibril contacts. We also show that exchangeable
      side-chain protons inside the hydrophobic core of HET-s(218-289) do not exchange
      over time intervals of weeks to months. The experiments proposed in this study
      can provide insight into the detailed structural features of amyloid fibrils in
      general.

PMID- 21094165
TI  - Visualizing active-site dynamics in single crystals of HePTP: opening of the WPD
      loop involves coordinated movement of the E loop.
AB  - Phosphotyrosine hydrolysis by protein tyrosine phosphatases (PTPs) involves
      substrate binding by the PTP loop and closure over the active site by the WPD
      loop. The E loop, located immediately adjacent to the PTP and WPD loops, is
      conserved among human PTPs in both sequence and structure, yet the role of this
      loop in substrate binding and catalysis is comparatively unexplored.
      Hematopoietic PTP (HePTP) is a member of the kinase interaction motif (KIM) PTP
      family. Compared to other PTPs, KIM-PTPs have E loops that are unique in both
      sequence and structure. In order to understand the role of the E loop in the
      transition between the closed state and the open state of HePTP, we identified a
      novel crystal form of HePTP that allowed the closed-state-to-open-state
      transition to be observed within a single crystal form. These structures, which
      include the first structure of the HePTP open state, show that the WPD loop
      adopts an 'atypically open' conformation and, importantly, that ligands can be
      exchanged at the active site, which is critical for HePTP inhibitor development.
      These structures also show that tetrahedral oxyanions bind at a novel secondary
      site and function to coordinate the PTP, WPD, and E loops. Finally, using both
      structural and kinetic data, we reveal a novel role for E-loop residue Lys182 in
      enhancing HePTP catalytic activity through its interaction with Asp236 of the WPD
      loop, providing the first evidence for the coordinated dynamics of the WPD and E
      loops in the catalytic cycle, which, as we show, is relevant to multiple PTP
      families.

PMID- 21094167
TI  - Stabilizing the eIF4G1 alpha-helix increases its binding affinity with eIF4E:
      implications for peptidomimetic design strategies.
AB  - Eukaryotic initiation factor (eIF)4E is overexpressed in many types of cancer
      such as breast, head and neck, and lung. A consequence of increased levels of
      eIF4E is the preferential translation of pro-tumorigenic proteins such as c-Myc,
      cyclin D1, and vascular endothelial growth factor. Inhibition of eIF4E is
      therefore a potential therapeutic target for human cancers. A novel peptide based
      on the eIF4E-binding peptide eIF4G1, where the alpha-helix was stabilized by the
      inclusion of alpha-helix inducers as shown by CD measurements, was synthesized.
      The helically stabilized peptide binds with an apparent K(d) of 9.43+/-2.57 nM,
      which is ~15.7-fold more potent than the template peptide from which it is
      designed. The helically stabilized peptide showed significant biological activity
      at a concentration of 400 MUM, unlike the naturally occurring eIFG1 peptide when
      measured in cell-based cap-dependent translational reporter and WST-1 (4-[3-(4
      iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assays.
      Fusion of the template peptide and the stabilized peptide to the cell-penetrating
      peptide TAT produced more active but equally potent inhibitors of cap-dependent
      translation in cell lines. They also equally disrupted cell metabolism as
      measured in a WST-1 assay. Propidium iodide staining revealed that the TAT-fused,
      helically stabilized peptide caused more cell death than the TAT-fused eIF4G1
      template peptide with substantial decreases in the G1 and G2 cell populations.
      Annexin-staining experiments also indicated that the TAT-fused eIF4G1 derivative
      peptides caused cell death by apoptosis. The results presented should offer
      further insight into peptidomimetics development for eIF4E.

PMID- 21094166
TI  - Structural and functional conservation of Mycobacterium tuberculosis GroEL
      paralogs suggests that GroEL1 Is a chaperonin.
AB  - GroEL is a group I chaperonin that facilitates protein folding and prevents
      protein aggregation in the bacterial cytosol. Mycobacteria are unusual in
      encoding two or more copies of GroEL in their genome. While GroEL2 is essential
      for viability and likely functions as the general housekeeping chaperonin, GroEL1
      is dispensable, but its structure and function remain unclear. Here, we present
      the 2.2-A resolution crystal structure of a 23-kDa fragment of Mycobacterium
      tuberculosis GroEL1 consisting of an extended apical domain. Our X-ray structure
      of the GroEL1 apical domain closely resembles those of Escherichia coli GroEL and
      M. tuberculosis GroEL2, thus highlighting the remarkable structural conservation
      of bacterial chaperonins. Notably, in our structure, the proposed substrate
      binding site of GroEL1 interacts with the N-terminal region of a symmetry-related
      neighboring GroEL1 molecule. The latter is consistent with the known GroEL apical
      domain function in substrate binding and is supported by results obtained from
      using peptide array technology. Taken together, these data show that the apical
      domains of M. tuberculosis GroEL paralogs are conserved in three-dimensional
      structure, suggesting that GroEL1, like GroEL2, is a chaperonin.

PMID- 21094168
TI  - Multistability in an age-structured model of hematopoiesis: Cyclical neutropenia.
AB  - Cyclical neutropenia (CN) is a rare hematopoietic disorder in which the patient's
      neutrophil level drops to extremely low levels for a few days approximately every
      three weeks. CN is effectively treated with granulocyte colony stimulating factor
      (G-CSF), which is known to interfere with apoptosis in neutrophil precursors and
      to consequently increase the circulating neutrophil level. However, G-CSF
      treatment usually fails to eliminate the oscillation. In this study, we establish
      an age-structured model of hematopoiesis, which reduces to a set of four delay
      differential equations with specific forms of initial functions. We numerically
      investigate the possible stable solutions of the model equations with respect to
      changes in the parameters as well as the initial conditions. The results show
      that the hematopoietic system possesses multistability for parameters typical of
      the normal healthy state. From our numerical results, decreasing the
      proliferation rate of neutrophil precursors or increasing the stem cell death
      rate are two possible mechanisms to induce cyclical neutropenia, and the periods
      of the resulting oscillations are independent of the changing parameters. We also
      discuss the dependence of the model solution on the initial condition at normal
      parameter values corresponding to a healthy state. Using insight from our results
      we design a hybrid treatment method that is able to abolish the oscillations in
      CN.

PMID- 21094169
TI  - Outbreak properties of epidemic models: the roles of temporal forcing and
      stochasticity on pathogen invasion dynamics.
AB  - Despite temporally forced transmission driving many infectious diseases,
      analytical insight into its role when combined with stochastic disease processes
      and non-linear transmission has received little attention. During disease
      outbreaks, however, the absence of saturation effects early on in well-mixed
      populations mean that epidemic models may be linearised and we can calculate
      outbreak properties, including the effects of temporal forcing on fade-out,
      disease emergence and system dynamics, via analysis of the associated master
      equations. The approach is illustrated for the unforced and forced SIR and SEIR
      epidemic models. We demonstrate that in unforced models, initial conditions (and
      any uncertainty therein) play a stronger role in driving outbreak properties than
      the basic reproduction number R0, while the same properties are highly sensitive
      to small amplitude temporal forcing, particularly when R0 is small. Although
      illustrated for the SIR and SEIR models, the master equation framework may be
      applied to more realistic models, although analytical intractability scales
      rapidly with increasing system dimensionality. One application of these methods
      is obtaining a better understanding of the rate at which vector-borne and
      waterborne infectious diseases invade new regions given variability in
      environmental drivers, a particularly important question when addressing
      potential shifts in the global distribution and intensity of infectious diseases
      under climate change. 

PMID- 21094170
TI  - A lysine-free mutant of epidermal growth factor as targeting moiety of a targeted
      toxin.
AB  - AIMS: Elevated levels of epidermal growth factor (EGF) receptor are observed on
      several human tumors, e.g. cervical carcinoma and mamma carcinomas. The natural
      ligand EGF is an alternative to established antibodies and tyrosine kinase
      inhibitors for targeting EGF receptor-overexpressing tumor cells for therapy.
      Conjugations of compounds to EGF lack the necessary homogeneity for an intended
      application, since several amino acids may react with the chemical linker. MAIN
      METHODS: We designed an EGF variant (EGF(RR)) in which the two lysines were
      substituted with arginine (K28R and K48R). EGF(RR) was fused to the protein toxin
      saporin to obtain a model protein for detailed analyses on EGF receptor binding
      and on both the enzymatic activity of saporin and the cytotoxicity of the fusion
      protein. KEY FINDINGS: The mutation decreased the enzymatic activity of saporin
      2.3-fold and the binding of EGF(RR) retained its specificity for EGF receptor
      while increasing the Kd 5.5-fold. In spite of these differences the cytotoxicity
      of the fusion protein was unchanged in comparison to a fusion protein with EGF
      both when applied alone and in combination with cytotoxicity augmenting saponin.
      SIGNIFICANCE: We conclude that EGF(RR) retained its ability to bind with high
      specificity to EGF receptor and is thus suitable for a number of chemical linkage
      applications such as targeting drugs or dyes to EGF receptor-expressing cells.

PMID- 21094171
TI  - Identification of serum proteins involved in pancreatic cancer cachexia.
AB  - AIMS: Treatment of cachexia requires pharmacological intervention which, in turn,
      requires knowledge of the mediators and processes. Cachexia markers that are
      specifically expressed in pancreatic cancer and secreted into the blood
      circulation have yet to be identified. The aim of our study was to investigate
      the serum protein profiles and protein alterations associated with cachexia and
      to identify potential disease protein biomarkers indicative for this syndrome.
      MAIN METHODS: Serum samples from cachectic and non-cachectic patients undergoing
      pancreatic cancer (PaCa) surgery and controls were investigated by Surface
      Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF
      MS). The identity of detected discriminatory markers was determined by a
      combination of protein fractionation, chromatographic purification steps, gel
      electrophoresis, and mass spectrometry. KEY FINDINGS: Using Cu-IMAC array and CM
      10 array based SELDI-TOF-MS. we identified eleven up- and four down-regulated
      proteins associated with cachexia. CiphergenExpress analysis revealed four
      disease-associated protein features (38559Da, 9138Da, 8925Da and 3358Da) that
      were elevated by a factor of 2.3, 1.7, 1.4 and 1.4, respectively. Zinc-alpha2
      glycoprotein (ZAG), apolipoproteins apo C-II and apo C-III and glucagon-like
      peptide-1 (GLP-1) were identified as markers for PaCa-associated cachexia
      syndrome. ZAG levels were additionally evaluated in serum and tissue samples by
      ELISA and immunohistochemistry and the obtained data confirmed the SELDI-TOF-MS
      results. SIGNIFICANCE: The identified proteins could be routinely and reliably
      measured in the serum of patients and provide an elegant non-invasive approach
      for early diagnosis of cachectic pancreatic cancer patients. Controlling ZAG and
      GLP-1 activity could be beneficial in the management of cancers and cachexia
      induced conditions.

PMID- 21094172
TI  - Mouse mesenchymal stem cells from bone marrow differentiate into smooth muscle
      cells by induction of plaque-derived smooth muscle cells.
AB  - AIM: The present study aimed to elucidate the mechanism by which bone marrow
      mesenchymal stem cells (BMSCs) differentiate into smooth muscle cells (SMCs) in
      atherosclerosis. MAIN METHODS: We isolated mouse BMSCs and incubated them in
      conditioned medium from plaque-derived SMCs (SMC-CM) and analyzed growth factors
      from media. BMSCs were treated with different media and harvested at continuous
      time points for investigating the ability to differentiate toward SMCs. Next,
      BMSCs of green fluorescence protein (GFP) mice were transplanted into
      apolipoprotein E(-/-) (apoE(-/-)) mice fed on western type diet for 12 weeks. In
      vivo efficacy of BMSCs was investigated. KEY FINDINGS: After being cultured using
      SMC-CM, hepatocyte growth factor (HGF) was abundantly secreted into the medium by
      BMSCs with time. BMSCs had increased expression of HGF receptor c-met and SMC
      specific markers while they also displayed SMC characteristic 'hill and valley
      like' appearance with an SMC ultra-structure including actin filaments and dense
      bodies. In vivo-grafted BMSCs aggravated atherosclerotic lesions and inflammation
      but ameliorated fibrosis in aorta while they displayed higher expression levels
      of c-met and early SMC-specific markers but not late-stage markers in aorta. They
      also demonstrated greater secretion of HGF in the aorta of apoE(-/-) mice.
      Furthermore, when BMSCs were treated with HGF blocking antibody, they lost the
      ability to differentiate to SMCs. SIGNIFICANCE: HGF from local SMCs plays an
      important role for the differentiation of homing BMSCs.

PMID- 21094173
TI  - A mechanism by which the osmotic laxative magnesium sulphate increases the
      intestinal aquaporin 3 expression in HT-29 cells.
AB  - AIMS: We have suggested that an osmotic laxative, magnesium sulphate (MgSO(4)),
      may act as a cathartic in a very rational manner by increasing the aquaporin 3
      (AQP3) expression level and by changing osmotic pressure in the colon. In this
      study, we examined the mechanism by which MgSO(4) increases the intestinal AQP3
      expression level by using the human colon cancer HT-29 cell line. MAIN METHODS:
      After the addition of MgSO(4) to HT-29 cells, the expression levels of AQP3 mRNA
      and protein were measured using real-time RT-PCR and western blotting,
      respectively. The intracellular Mg(2+) concentration, adenylate cyclase (AC)
      activity and protein kinase A (PKA) activity were also determined. The
      phosphorylated cAMP response element-binding protein (CREB) expression levels
      were determined by western blotting. KEY FINDINGS: The AQP3 mRNA expression level
      started to increase significantly at 1 h after MgSO(4) addition and peaked at 9
      h, at a level 3 times as high as the control levels. The AQP3 protein expression
      level started to increase 6 h after the addition and reached a level almost twice
      as high as the control levels by hour 12. In the HT-29 cells treated with
      MgSO(4), there was a 1.4-fold increase in the intracellular Mg(2+) concentration,
      a 1.5-fold increase in AC activity, a 1.6-fold increase in PKA activity, and a
      significant increase in phosphorylation of the CREB. SIGNIFICANCE: These results
      suggest that the AC activation caused by an increase in the intracellular Mg(2+)
      concentration may trigger CREB phosphorylation through PKA activation and promote
      AQP3 gene transcription.

PMID- 21094174
TI  - Dynamic retinal vessel response to flicker in obesity: A methodological approach.
AB  - Obesity and related metabolic disorders affect vascular endothelial function. The
      use of the Dynamic Vessel Analyzer (DVA) represents a modern methodological
      approach to analyze vascular function in the retinal microcirculation. Whether
      the dynamic reaction to flicker stimulation in retinal vessels is altered in
      obese subjects is investigated. Retinal vessel reactions to flicker stimulation
      were examined by DVA in 46 obese individuals (49.6+/-10.0years) and 46 age- and
      gender-matched healthy controls. The clinical examination included anthropometry,
      blood pressure measurements and blood sampling. Mean maximal arteriolar dilation
      in response to flicker was reduced in the obese group (3.2+/-1.8%) compared to
      controls (4.1+/-2.0%, p<0.05) and the time to maximal arteriolar dilation was
      prolonged (18.0+/-9.4s vs. 14.6+/-3.8s, p=0.03). In addition, mean maximal
      venular dilation was reduced in obese subjects (3.9+/-1.7% vs. 4.7+/-1.8%,
      p<0.05). Among the microvascular parameters, the most significant correlation
      with waist circumference was found for the "area under the reaction curve 50-80s
      after stimulation" in arterioles (r=-0.40; p<0.001). Functional retinal
      arteriolar reactivity to flicker stimulation differs between obese and healthy
      lean subjects. Time course analysis of retinal vessel response and its
      quantitative parameters can comprehensively characterize alterations of retinal
      vessel reactivity in metabolic disease.

PMID- 21094175
TI  - Cytosolic and calcium-independent phospholipase A(2) mediate glioma-enhanced
      proangiogenic activity of brain endothelial cells.
AB  - Glioma is characterized by an active production of proangiogenic molecules. We
      observed that conditioned medium (CM) from C6 glioma significantly enhanced
      proliferation and migration of immortalized rat brain GP8.3 endothelial cells
      (ECs) and primary bovine brain microvascular ECs. The glioma CM effect was
      significantly reduced by cytosolic (cPLA(2)) and Ca(++)-independent (iPLA(2))
      phospholipase A(2), cyclooxygenase-2, and protein kinase inhibitors. In GP8.3
      ECs, cPLA(2) and iPLA(2) enzyme activities and phosphorylation of cPLA(2),
      significantly stimulated after 24h CM co-incubation, were attenuated by PLA(2),
      PI3-K, MEK-1, and ERK1/2 inhibitors. By confocal microscopy, in glioma CM
      stimulated ECs, enhancement of fluorescence signals for phospho-cPLA(2), phospho
      ERK1/2, phospho-PKCalpha, COX-2, and iPLA(2) was in parallel observed.
      Electroporation of anti-iPLA(2) and cPLA(2) antibodies and siRNAs directed
      against iPLA(2) and cPLA(2) significantly inhibited cell proliferation and
      migration. Incubation of CM- or VEGF peptide-stimulated ECs with antibodies
      against VEGF or VEGFR-1/-2 receptors strongly reduced mitotic rate, cell
      migration, and phospho-cPLA(2) and iPLA(2) protein levels. The findings suggest
      that PLA(2) activities are involved in stimulating EC migration and proliferation
      in the presence of glioma CM and that cPLA(2) is positively regulated upstream by
      PI3-K, PKCalpha, and ERK1/2 signal cascades. Our work provides new insights in
      understanding EC metabolism and signaling during tumor angiogenesis.

PMID- 21094176
TI  - Correlated deficits of perception and action in optic ataxia.
AB  - Optic ataxia, following dorsal stream lesions, is characterised by impaired
      visuomotor guidance. Recent studies have found concurrent perceptual deficits,
      but it is unclear whether these are functionally related to the visuomotor
      symptoms. We studied the ability of a well-documented patient (IG) with bilateral
      optic ataxia to react to sudden target jumps by correcting ongoing reaches or by
      explicitly reporting the jump direction. IG showed deficient reach corrections,
      especially for target jumps to the visual periphery, and was similarly slow to
      discriminate the same jumps perceptually. Across six test conditions, in which
      the retinal locations of target jumps were varied, her perceptual slowing
      mirrored her reaching deficit precisely. These findings confirm perceptual
      impairments after dorsal stream lesions, and imply a shared functional basis with
      the classical visuomotor symptoms of optic ataxia. Additionally, we show that the
      online correction deficit is determined dually by the retinal location to which
      the reach must be diverted, and the location to which it is initially directed.
      We suggest that this deficit, and its perceptual counterpart, can be traced to a
      slowed contralesional orienting of attention in optic ataxia.

PMID- 21094177
TI  - Neuromodulation of multisensory perception: a tDCS study of the sound-induced
      flash illusion.
AB  - This study explores whether brain polarization could be effective in modulating
      multisensory audiovisual interactions in the human brain, as measured by the
      'sound-induced flash illusion' (Shams et al., 2000). In different sessions,
      healthy participants performed the task while receiving anodal, cathodal, or sham
      tDCS (2 mA, 8 min) to the occipital, temporal, or posterior parietal cortices. We
      found that up- or down-regulating cortical excitability by tDCS can facilitate or
      reduce audiovisual illusions, depending on the current polarity, the targeted
      area, and the illusory percept. Specifically, the perceptual 'fission' of a
      single flash, due to multiple beeps, was increased after anodal tDCS of the
      temporal cortex, and decreased after anodal stimulation of the occipital cortex.
      A reversal of such effects was induced by cathodal tDCS. Conversely, the
      perceptual 'fusion' of multiple flashes due to a single beep was unaffected by
      tDCS. This evidence adds novel clues on the cortical substrate of the generation
      of the sound-flash illusion, and opens new attractive possibilities for
      modulating multisensory perception in humans: tDCS appears to be an effective
      tool to modulate the conscious visual experience associated with multisensory
      interactions, by noninvasively shifting cortical excitability within occipital or
      temporal areas.

PMID- 21094178
TI  - Genetic differences in emotionally enhanced memory.
AB  - Understanding genetic contributions to individual differences in the capacity for
      emotional memory has tremendous implications for understanding normal human
      memory as well as pathological reactions to traumatic stress. Research in the
      last decade has identified genetic polymorphisms thought to influence
      cognitive/affective processes that may contribute to emotional memory capacity.
      In this paper, we review key polymorphisms linked to emotional and mnemonic
      processing and their influence on neuromodulator activity in the amygdala and
      other emotion-related structures. We discuss their potential roles in specific
      cognitive processes involved in memory formation, and review links between these
      genetic variants, brain activation, and specific patterns of attention,
      perception, and memory consolidation that may be linked to individual differences
      in memory vividness. Finally we propose a model predicting an influence of
      noradrenergic, serotonergic, and dopaminergic processes on emotional perception,
      as well as on memory consolidation and self-regulation. Outside of the
      laboratory, it is likely that real-life effects of arousal operate along a
      continuum that incorporates other "non-emotional" aspects of memory. For this
      reason we further discuss additional literature on genetic variations that
      influence general episodic memory processes, rather than being specific to
      emotional enhancement of memory. We conclude that specific neuromodulators
      contribute to an amygdala-driven memory system that is relatively involuntary,
      embodied, and sensorily vivid.

PMID- 21094179
TI  - Exploiting the potential of three dimensional spatial wavelet analysis to explore
      nesting of temporal oscillations and spatial variance in simultaneous EEG-fMRI
      data.
AB  - Synchronization of the activity in neural networks is a fundamental mechanism of
      brain function, putatively serving the integration of computations on multiple
      spatial and temporal scales. Time scales are thought to be nested within distinct
      spatial scales, so that whereas fast oscillations may integrate local networks,
      slow oscillations might integrate computations across distributed brain areas. We
      here describe a newly developed approach that provides potential for the further
      substantiation of this hypothesis in future studies. We demonstrate the
      feasibility and important caveats of a novel wavelet-based means of relating time
      series of three-dimensional spatial variance (energy) of fMRI data to time series
      of temporal variance of EEG. The spatial variance of fMRI data was determined by
      employing the three-dimensional dual-tree complex wavelet transform. The temporal
      variance of EEG data was estimated by using traditional continuous complex
      wavelets. We tested our algorithm on artificial signals with known signal-to
      noise ratios and on empirical resting state EEG-fMRI data obtained from four
      healthy human subjects. By employing the human posterior alpha rhythm as an
      exemplar, we demonstrated face validity of the approach. We believe that the
      proposed method can serve as a suitable tool for future research on the
      spatiotemporal properties of brain dynamics, hence moving beyond analyses based
      exclusively in one domain or the other.

PMID- 21094180
TI  - Light-induced phosphorylation of crystallins in the retinal pigment epithelium.
AB  - Protein phosphorylations have essential regulatory roles in visual signaling.
      Previously, we found that phosphorylation of several proteins in the retina and
      retinal pigment epithelium (RPE) is involved in anti-apoptotic signaling under
      oxidative stress conditions, including light exposure. In this study, we used a
      phosphoprotein enrichment strategy to evaluate the light-induced phosphoproteome
      of primary bovine RPE cells. Phosphoprotein-enriched extracts from bovine RPE
      cells exposed to light or dark conditions for 1h were separated by 2D SDS-PAGE.
      Serine and tyrosine phosphorylations were visualized by 2D phospho Western
      blotting and specific phosphorylation sites were analyzed by tandem mass
      spectrometry. Light induced a marked increase in tyrosine phosphorylation of beta
      crystallin A3 and A4. The most abundant light-induced up-regulated
      phosphoproteins were crystallins of 15-25 kDa, including beta crystallin S and
      zeta crystallin. Phosphorylation of beta crystallin suggests an anti-apoptotic
      chaperone function of crystallins in the RPE. Other chaperones, cytoskeletal
      proteins, and proteins involved in energy balance were expressed at higher levels
      in the dark. A detailed analysis of RPE phosphoproteins provides a molecular
      basis for understanding of light-induced signal transduction and anti-apoptosis
      mechanisms. Our data indicates that phosphorylation of crystallins likely
      represents an important mechanism for RPE shielding from physiological and
      pathophysiological light-induced oxidative injury.

PMID- 21094181
TI  - The information transfer system of halophilic archaea.
AB  - Information transfer is fundamental to all life forms. In the third domain of
      life, the archaea, many of the genes functioning in these processes are similar
      to their eukaryotic counterparts, including DNA replication and repair, basal
      transcription, and translation genes, while many transcriptional regulators and
      the overall genome structure are more bacterial-like. Among halophilic (salt
      loving) archaea, the genomes commonly include extrachromosomal elements, many of
      which are large megaplasmids or minichromosomes. With the sequencing of genomes
      representing ten different genera of halophilic archaea and the availability of
      genetic systems in two diverse models, Halobacterium sp. NRC-1 and Haloferax
      volcanii, a large number of genes have now been annotated, classified, and
      studied. Here, we review the comparative genomic, genetic, and biochemical work
      primarily aimed at the information transfer system of halophilic archaea,
      highlighting gene conservation and differences in the chromosomes and the large
      extrachromosomal elements among these organisms.

PMID- 21094182
TI  - An integrative model of tinnitus based on a central gain controlling neural
      sensitivity.
AB  - The purpose of the current review is to propose a model highlighting the putative
      connections between hearing loss and the phantom perception of tinnitus (tinnitus
      being accompanied by hearing loss in the majority, if not all, subjects). Sensory
      deprivation is followed by dramatic functional and structural changes in the
      auditory system. Notably, while cochlear injuries are accompanied by a reduced
      activity in the cochlear nerve, neural activity is increased at virtually all
      levels in the central auditory system. We suggest that this central hyperactivity
      could result from a central gain increase; the general purpose of this gain
      modulation being to adapt neural sensitivity to the reduced sensory inputs,
      preserving a stable mean firing and neural coding efficiency. However,
      maintaining neural homeostasis at all costs, in the event of an auditory system
      sensory deprivation, could be done at the price of amplifying "neural noise" due
      to the overall increase of gain (or sensitivity), ultimately resulting in the
      generation of tinnitus. The clinical implications of this model are also
      presented.

PMID- 21094183
TI  - Epidemiology of Haemophilus influenzae bacteremia: a multi-national population
      based assessment.
AB  - OBJECTIVES: Haemophilus influenzae is an important cause of invasive infection
      but contemporary data in non-selected populations is limited. METHODS: Population
      based surveillance for Haemophilus influenzae bacteremia was conducted in seven
      regions in Australia, Canada, and Denmark during 2000-2008. RESULTS: The overall
      annual incidence rate was 1.31 per 100,000 population and type specific rates
      were 0.08 for H. influenzae serotype b (Hib), 0.22 for H. influenzae serotypes a,
      c-f (Hiac-f), and 0.98 per 100,000 for non-typeable H. influenzae (NTHi). Very
      young and old patients were at highest risk. The serotypes causing disease varied
      according to age with nearly all cases in the elderly due to NTHi. The presence
      of comorbid medical illness was common with 14%, 16%, and 29% patients having
      Charlson comorbidity scores of 1, 2, and >= 3, respectively. The 30-day all-cause
      case-fatality rate was 18%. Factors independently associated with death at 30
      days in logistic regression analysis included male gender, hospital-onset
      disease, older age, and lower respiratory tract, central nervous system, or
      unknown focus of infection. CONCLUSIONS: Haemophilus influenzae is an important
      cause of morbidity and mortality particularly with NTHi in the elderly. These
      data serve as a baseline to assess the future effectiveness of new preventative
      interventions.

PMID- 21094184
TI  - The role of particle size in aerosolised pathogen transmission: a review.
AB  - Understanding respiratory pathogen transmission is essential for public health
      measures aimed at reducing pathogen spread. Particle generation and size are key
      determinant for pathogen carriage, aerosolisation, and transmission. Production
      of infectious respiratory particles is dependent on the type and frequency of
      respiratory activity, type and site of infection and pathogen load. Further,
      relative humidity, particle aggregation and mucus properties influence expelled
      particle size and subsequent transmission. Review of 26 studies reporting
      particle sizes generated from breathing, coughing, sneezing and talking showed
      healthy individuals generate particles between 0.01 and 500 MUm, and individuals
      with infections produce particles between 0.05 and 500 MUm. This indicates that
      expelled particles carrying pathogens do not exclusively disperse by airborne or
      droplet transmission but avail of both methods simultaneously and current
      dichotomous infection control precautions should be updated to include measures
      to contain both modes of aerosolised transmission.

PMID- 21094185
TI  - Administration of BDNF/ginsenosides combination enhanced synaptic development in
      human neural stem cells.
AB  - Ginsenosides Rg1 and Rb1, major pharmacologically active ingredients from
      Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), were applied in the
      differentiation media for human neural stem cells (hNSCs), together with brain
      derived neurotrophic factor (BDNF), a commonly used compound for neural stem cell
      (NSC) differentiation. Cell locomotion and neurite extension were observed by
      time-lapse microscopy and analyzed by ImageJ software. The expression of synaptic
      formation was confirmed by immunostaining of synaptophysin (SYN) or/and the co
      localization of synapsin I and microtubule associated protein-2 (MAP-2). Effects
      of cell density on neural differentiation were also examined. Results have shown
      that administration of BDNF/ginsenosides (Rg1 and Rb1) combination in
      differentiation medium promoted cell survival, enhanced neurite outgrowth and
      synaptic marker expression during differentiation. High cell density enhanced
      synaptic marker expression in BDNF/ginsenosides combination medium. In all, this
      study established a condition for hNSCs synaptic development in early
      differentiation, which is a crucial step in applying this cell line in neural
      network-based assay.

PMID- 21094187
TI  - Inhibition of poxvirus spreading by the anti-tumor drug Gefitinib (Iressa).
AB  - The threat of smallpox virus as a bioterrorist weapon is raising international
      concerns again since the anthrax attacks in the USA in 2001. The medical
      readiness of treating patients suffering from such infections is a prerequisite
      of an effective civil defense system. Currently the only therapeutic option for
      the treatment of poxvirus infections relies on the virostatic nulceosid analog
      cidofovir, although severe side effects and drug resistant strains have been
      described. A growing understanding of poxvirus pathogenesis raises the
      possibility to explore other appropriate targets involved in the viral
      replication cycle. Poxvirus encoded growth factors such as the Vaccinia Growth
      Factor (VGF) stimulate host cells via the Epidermal Growth Factor Receptor (EGFR)
      and thereby facilitate viral spreading. In this study we could visualize for the
      first time the paracrine priming of uninfected cells for subsequent infection by
      orthopoxviruses directly linked to EGFR phosphorylation. Since EGFR is a well
      known target for anti-tumor therapy small molecules for inhibition of its
      tyrosine kinase (TK) activity are readily available and clinically evaluated. In
      this study we analyzed three different EGFR receptor tyrosine kinase inhibitors
      for inhibition of orthopoxvirus infection in epithelial cells. The inhibitor
      shown to be most effective was Gefitinib (Iressa) which is already approved as a
      drug for anti-tumor medication in the USA and in Europe. Thus Gefitnib may
      provide a new therapeutic option for single or combination therapy of acute
      poxvirus infections, acting on a cellular target and thus reducing the risk of
      viral resistance to treatment.

PMID- 21094186
TI  - Biological activity of truncated C-terminus human heat shock protein 72.
AB  - Heat shock protein 72 (Hsp72), a canonical intracellular molecular chaperone, may
      also function as an extracellular danger signal for the innate immune system. To
      further delineate the biological role of Hsp72 in the innate immune system, we
      generated two truncated versions of the full length human Hsp72 (N-terminus
      Hsp72, amino acids 1-430; and C-terminus Hsp72 amino acids 420-641) and directly
      compared their ability to activate cells from the macrophage/monocyte lineage. In
      RAW 264.7 macrophages transfected with a NF-kappaB-dependent luciferase reporter
      plasmid, C-terminus Hsp72 was a more potent inducer of NF-kappaB activity than N
      terminus Hsp72, and this effect did not seem to be secondary to endotoxin
      contamination. C-terminus Hsp72-mediated activation of the NF-kappaB pathway was
      corroborated by increased activation of IkappaB kinase, degradation of
      IkappaBalpha, and increased NF-kappaB-DNA binding. C-terminus Hsp72 was a more
      potent inducer of tumor necrosis factor-alpha (TNFalpha) expression in RAW 264.7
      macrophages and in primary murine peritoneal macrophages from wild-type mice. C
      terminus Hsp72 did not induce TNFalpha expression in primary murine peritoneal
      macrophages from Toll-like receptor (TLR4) mutant mice, indicating a role for
      TLR4. In human THP-1 mononuclear cells, C-terminus Hsp72 induced tolerance to
      subsequent LPS stimulation, whereas N-terminus Hsp72 did not induce tolerance.
      Finally, control experiments using equimolar amounts of N-terminus or C-terminus
      Hsp72 demonstrated a higher biological potency for C-terminus Hsp72. These data
      demonstrate that the ability of human Hsp72 to serve as an activator for cells of
      the macrophage/monocyte lineage primarily lies in the C-terminus region spanning
      amino acids 420-641.

PMID- 21094188
TI  - Environmental noise affects auditory temporal processing development and NMDA-2B
      receptor expression in auditory cortex.
AB  - Auditory temporal processing is essential for sound discrimination and speech
      comprehension. Under normal developmental conditions, temporal processing acuity
      improves with age. As recent animal studies have shown that the functional
      development of the auditory cortex (AC) is impaired by early life exposure to
      environmental noise (i.e., continuous, moderate-level, white noise), here we
      investigated whether the normal age-related improvement in temporal processing
      acuity is sensitive to delayed development of the AC. We used a behavioral
      paradigm, the gap-induced prepulse inhibition of the acoustic startle reflex, to
      assess the gap detection threshold, and provide a comparison of temporal
      processing acuity between environmental noise-reared rats and age-matched
      controls. Moreover, because age-related changes normally occur in the relative
      expression of different N-methyl-D-aspartate (NMDA) receptor subunits, we
      assessed the level of protein expression of NMDA-2A and 2B receptors (NR2A and
      NR2B respectively) in the AC after environmental noise-rearing. As hypothesized,
      rats reared in environmental noise showed (1) poor temporal processing acuity as
      adults (i.e., gap detection threshold remained elevated at a juvenile-like
      level), and (2) an increased level of NR2B protein expression compared to age
      matched controls. This poor temporal processing acuity represented delayed
      development rather than permanent impairment, as moving these environmental noise
      reared rats to normal acoustic conditions improved their gap detection threshold
      to an age-appropriate level. Furthermore, housing normally reared, adult rats in
      environmental noise for two months did not affect their already-mature gap
      detection threshold. Thus, masking normal sound inputs with environmental noise
      during early life, but not adulthood, impairs temporal processing acuity as
      assessed with the gap detection threshold.

PMID- 21094189
TI  - Genetic screening for bacterial mutants in liquid growth media by fluorescence
      activated cell sorting.
AB  - Many bacterial pathogens have defined in vitro virulence inducing conditions in
      liquid media which lead to production of virulence factors important during an
      infection. Identifying mutants that no longer respond to virulence inducing
      conditions will increase our understanding of bacterial pathogenesis. However,
      traditional genetic screens require growth on solid media. Bacteria in a single
      colony are in every phase of the growth curve, which complicates the analysis and
      makes screens for growth phase-specific mutants problematic. Here, we utilize
      fluorescence-activated cell sorting in conjunction with random transposon
      mutagenesis to isolate bacteria grown in liquid media that are defective in
      virulence activation. This method permits analysis of an entire bacterial
      population in real time and selection of individual bacterial mutants with the
      desired gene expression profile at any time point after induction. We have used
      this method to identify Vibrio cholerae mutants defective in virulence induction.

PMID- 21094190
TI  - Optimal methods for evaluating antimicrobial activities from plant extracts.
AB  - The search for antimicrobial agents from plants has been a growing interest in
      the last few decades. However, results generated from many of these studies
      cannot be directly compared due to the absence of standardization in particular
      antimicrobial methods employed. The need for established methods with consistent
      results for the evaluation of antimicrobial activities from plant extracts has
      been proposed by many researchers. Nevertheless, there are still many studies
      reported in the literature describing different methodologies. The aim of this
      study was to find optimal methods to give consistent quantitative antimicrobial
      results for studying plant extracts. Three different agar-based assays (pour
      plate disc diffusion (PPDD), streak plate disc diffusion (SPDD) and well-in agar
      (WA)) and one broth-based (turbidometric (TB)) assay were used in this study.
      Extracts from two plant species (Duabanga grandiflora and Acalypha wilkesiana)
      were tested on two bacterial species, namely Escherichia coli and Staphylococcus
      aureus. Amongst the agar-based assays, PPDD produced the most reproducible
      results. TB was able to show the inhibitory effects of the test samples on the
      growth kinetic of the bacteria including plant extracts with low polarity. We
      propose that both agar- (i.e PPDD) and broth-based assays should be employed when
      assessing the antimicrobial activity of plant crude extracts.

PMID- 21094191
TI  - Development of a liposomal nanoparticle formulation of 5-fluorouracil for
      parenteral administration: formulation design, pharmacokinetics and efficacy.
AB  - 5-Fluorouracil (5-FU) is a small, very membrane permeable drug that is poorly
      retained within the aqueous compartment of liposomal nanoparticles (LNP). To
      address this problem a novel method relying on formation of a ternary complex
      comprising copper, low molecular weight polyethylenimine (PEI) and 5-FU has been
      developed. More specifically, in the presence of entrapped copper and PEI,
      externally added 5-FU can be efficiently encapsulated (>95%) in DSPC/Chol (1,2
      Distearoyl-sn-Glycero-3-Phosphocholine/cholesterol; 55:45 mol%) liposomes (130
      170 nm) to achieve drug-to-lipid ratios of 0.1 (mol:mol). Drug release studies
      completed using this LNP formulation of 5-FU demonstrated significant
      improvements in drug retention in vitro and in vivo. Plasma concentrations of 5
      FU were 7- to 23-fold higher when the drug was administered intravenously to mice
      as the LNP 5-FU formulation compared to free 5-FU. Further, the therapeutic
      effects of the LNP 5-FU formulation, as determined in a HT-29 subcutaneous
      colorectal cancer model where treatment was given QDx5, was greater than that
      which could be achieved with free 5-FU when compared at equivalent doses. This is
      the first time an active loading method has been described for 5-FU. The use of
      ternary metal complexation strategy to encapsulate therapeutic agents may define
      a unique platform for preparation of LNP drug formulations.

PMID- 21094192
TI  - Pore formation and pore closure in poly(D,L-lactide-co-glycolide) films.
AB  - Pore formation and pore closure in poly(D,L-lactide-co-glycolide)-based drug
      delivery systems are two important processes as they control the release of the
      encapsulated drug. The phenomenon pore closure was investigated by studying the
      effects of the pH and the temperature of the release medium, and the properties
      of the polymer. Poly(D,L-lactide-co-glycolide) (PLG) films were subjected to a
      pore forming pre-treatment, and then pore closure was observed simultaneously
      with changes in glass transition temperature, wettability (contact angle), water
      absorption and mass remaining. To further understand the effect of pH, combined
      pore formation and pore closure were studied at different pH values. Pore closure
      was increased in a release medium with low pH, with a low-molecular-weight PLG of
      relatively low degree of hydrophobicity, or at high temperature. Pore closure
      occurred by two different mechanisms, one based on polymer-polymer interactions
      and one on polymer-water interactions. The mobility of the PLG chains also played
      an important role. The surface of the PLG films were more porous at pH 5-6 than
      at lower or higher pH, as pore formation was relatively fast and pore closure
      were less pronounced in this pH range. The pH had a significant impact on the
      porous structure, which should be kept in mind when evaluating experimental
      results, as the pH may be significantly decreased in vitro, in vivo and in situ.
      The results also show that the initial porosity is very important when using a
      high-molecular-weight PLG.

PMID- 21094193
TI  - Impact of simulated ostracism on overweight and normal-weight youths' motivation
      to eat and food intake.
AB  - There is growing evidence that the experience of being ostracized can impair
      individuals' abilities to self-regulate, which in turn, leads to negative health
      behaviors, such as increased unhealthy eating. Research has focused on adults,
      but deficits in eating regulation in response to ostracism may be particularly
      detrimental for overweight or obese youth. This study examines the effects of a
      brief episode of ostracism on the motivation to eat and food intake of overweight
      and normal-weight young adolescents (M age=13.6 years). A computerized ball
      tossing game (Cyberball) was used to induce ostracism or inclusion. Following the
      inclusion/ostracism manipulation, all participants completed an operant computer
      task to earn points exchangeable for portions of food or for time socializing
      with an unfamiliar peer. Participants' responses for food and their subsequent
      energy intake were recorded. As hypothesized, ostracized overweight participants
      responded more for food and had a greater energy intake than overweight
      participants in the inclusion/control condition; whereas this was not the case
      for normal-weight participants. These results are important as studies indicate
      that overweight and obese youth may be at risk of social isolation and peer
      difficulties. Social adversity, if left unchanged, may increase the difficulty of
      promoting long-term changes in overweight youths' health behaviors.

PMID- 21094194
TI  - Eating rate of commonly consumed foods promotes food and energy intake.
AB  - We investigated the eating rate of commonly consumed foods and the associations
      with food intake and macronutrient composition. Ingestion time (s) of 50 g of 45
      foods was measured to assess eating rate (g/min), after which ad libitum food
      intake (g) was measured. Thirteen men and 24 women (aged 23.3 (SD 3.4)y, BMI 21.7
      (SD 1.7)kg/m(2)) participated, each testing 7 foods in separate sessions. We
      observed large differences in eating rate between foods, ranging from 4.2 (SD
      3.7) to 631 (SD 507)g/min. Eating rate was positively associated with food intake
      (beta=0.55) and energy intake (beta=0.001). Eating rate was inversely associated
      with energy density (beta=-0.00047) and positively with water content
      (beta=0.011). Carbohydrate (beta=-0.012), protein (beta=-0.021) and fiber content
      (beta=-0.087) were inversely associated with eating rate, whereas fat was not.
      This study showed that when foods can be ingested rapidly, food and energy intake
      is high. People may therefore be at risk of overconsumption, when consuming foods
      with a high eating rate. Considering the current food supply, where many foods
      have a high eating rate, long-term effects of eating rate on energy balance
      should be investigated.

PMID- 21094195
TI  - The effects of tailored and threatening nutrition information on message
      attention. Evidence from an event-related potential study.
AB  - Recent evidence indicates that attention is higher for individually tailored as
      compared to non-tailored health communications. The present study examined
      whether the predicted increased attention for the tailored as opposed to general
      nutrition education messages is moderated by presenting high vs. low threat
      information about the negative consequences of an unhealthy diet. In a mixed
      subject experimental design, undergraduate students (N=34) were reading tailored
      and non-tailored nutrition education messages with either high or low threat
      information about the negative consequences of an unhealthy diet. At the same
      time, they had to pay attention to specific odd auditory stimuli in a sequence of
      frequent auditory stimuli (oddball paradigm). The amount of attention allocation
      was measured by recording event-related potentials (ERPs; i.e., N100, MMN, P300)
      and reaction times. Result revealed main effects of tailoring and threat,
      indicating that more attention resources were allocated to tailored vs. non
      tailored messages and to low threat vs. high threat messages. The findings
      confirm that tailoring is an effective means to draw attention to health
      messages, whereas threat information seems to result in a loss in message
      attention.

PMID- 21094196
TI  - Ghrelin inhibits insulin resistance induced by glucotoxicity and lipotoxicity in
      cardiomyocyte.
AB  - Ghrelin has wide effects on cardiovascular and endocrine system. The aims of this
      study are to investigate the direct damage effect of high glucose and high
      palmitate on cardiomyocyte, and to study the effect of ghrelin on insulin
      resistance induced by glucotoxicity/lipotoxicity in cardiomyocyte and the
      possible mechanism underlying the cardioprotective activities of ghrelin. The
      changes of [(3)H]-2-deoxy-d-glucose ((3)H-G) intake rates were detected by
      isotope tracer method and the gene expressions in insulin signal transduction
      pathway were detected by real-time PCR and Western blot assay. The (3)H-G intake
      rate significantly reduced in high glucose (25mmol/l) or high palmitate
      (0.5mmol/l) treated primary rat ventricular myocytes. After the treatment of
      ghrelin (10(-7)mol/l), the (3)H-G intake rate recovered to the normal level. In
      addition, the phosphorylation of AKT occurred in 10min and was the highest in
      30min after the stimulation with ghrelin, which can be blocked by
      phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. Ghrelin also increased the
      mRNA levels of glucose transporter 4 (GLUT4), peroxisome proliferators (PPARr)
      and AMP activated protein kinase (AMPK) genes in insulin signal transduction
      pathway. These results indicate that the direct damage of high glucose and high
      palmitate on cardiomyocyte might be through insulin resistance (IR). Ghrelin can
      inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway. This
      may provide a clue for therapy for myocardial disease in diabetes mellitus.

PMID- 21094197
TI  - Quantification of estragole in fennel herbal teas: implications on the assessment
      of dietary exposure to estragole.
AB  - Quantification of estragole content in commercial fennel herbal teas was carried
      out in order to allow for a more accurate estimate of the dietary exposure to
      estragole. A simple and rapid analytical method, based on Stir Bar Sorptive
      Extraction and GC-MS, was developed for this purpose. Fennel teas obtained from
      different types of commercial products were analysed. Concentration levels ranged
      from 241 to 2058 MUg L(-1) in teas from teabags, from 9 to 912 MUg L(-1) in
      diluted instant teas, from 251 to 1718 MUg L(-1) in teas from not packaged seeds.
      Based on these data and considering the daily consumption of three portions of
      herbal tea, a maximum exposure to estragole for adults of 10 MUg/kg bw/day was
      calculated. The relatively high level observed in diluted instant teas of some
      brands deserves attention since these products are designed for infant
      consumption. Estimated exposure in infants was up to 51 MUg/kg bw/day for teas
      from teabags, and up to 23 MUg/kg bw/day for instant teas. A generalization of
      the use of suitable technologies in production processes of instant teas could
      substantially reduce the exposure to estragole in the vulnerable population
      groups (infants, young children, pregnant and breastfeeding women) who consume
      these products.

PMID- 21094198
TI  - Cellular glutathione content modulates the effect of andrographolide on beta
      naphthoflavone-induced CYP1A1 mRNA expression in mouse hepatocytes.
AB  - We previously reported that andrographolide (Andro), a major bioactive
      constituent of Andrographis paniculata, synergistically enhanced the inducible
      expression of CYP1A1 mRNA. In this study, although the synergism was confirmed at
      24h after the start of treatment with Andro and beta-naphthoflavone (betaNF), a
      CYP1A inducer, the expression was profoundly suppressed at an earlier phase,
      namely at 6-12h, when the betaNF-induced expression peaked. Although oxidized
      glutathione (GSSG) levels were higher in co-treated cells at 6 and 24h, levels of
      reactive oxygen species varied depending on the treatment period and species,
      indicating no relation to the synergistic expression of CYP1A1 mRNA. Glutathione
      (GSH) and N-acetyl-l-cysteine (NAC) significantly enhanced the betaNF-induced
      expression, and partly reversed the suppressive effect of Andro in the early
      phase. At 24h, the addition of GSH or NAC had no effect on betaNF-induced CYP1A1
      mRNA expression, but significantly reduced the synergistic effect of Andro. The
      synergistic effect was enhanced by l-buthionine-(S,R)-sulfoximine, a GSH
      depleter. Furthermore, H(2)O(2) and ascorbic acid further modified the profile of
      synergism of Andro on betaNF-inducible CYP1A1 mRNA expression. These results
      suggest that GSH status might be involved in betaNF-induced CYP1A1 mRNA
      expression, and the interaction of Andro with GSH might modulate the expression.

PMID- 21094199
TI  - Modifications of the organic and mineral fractions of dental tissues following
      conditioning by self-etching adhesives.
AB  - OBJECTIVES: Our objective was to analyse the acid strengths and concentrations in
      contemporary self-etch adhesives and test whether the adhesion/decalcification
      concept functions the same way for all products. METHODS: The self-etching
      adhesives were dissolved in a 50% water-ethanol solvent, these were reacted with
      biological apatite (HA) in the form of powder of human dentine in order to
      quantify calcium release and study the reaction products as a function of acid
      strengths and concentrations. The four self-etching adhesives investigated were
      AdheSE One (Ivoclar Vivadent, Schaan, Liechtenstein), Adper Easy Bond (3M ESPE,
      St Paul, MN, USA), Optibond All-In-One (KERR, Orange, CA, USA), Xeno V (Dentsply
      De Trey, Konstanz, Germany). RESULTS: Acid concentrations were found to span the
      range from 1 to 2 mmol/l, and the acid dissociation constants varied between
      apparent pKa values of 3.4 and 4.2. The pH values changed with time from values
      near 2.8 to 3.6, confirming the buffering action of HA. The stronger acids
      dissolved more calcium ions but left less organic matter attached to the tissue
      particles. Thermogravimetric and infrared analysis demonstrated that the weaker
      acids tended to bind to HA surfaces and increased significantly the organic to
      mineral ratios of the powders. CONCLUSION: Self-etching adhesives can be
      differentiated and classified in two types: weak acids attach to the mineral
      phase and leach little calcium; strong acids bind to the calcium ions,
      demineralize more and tend to debond from the dentinal hard tissues by forming
      more soluble calcium salts.

PMID- 21094200
TI  - Mental rotation in female fraternal twins: Evidence for intra-uterine hormone
      transfer?
AB  - Men outperform women in mental rotation by about one standard deviation. Prenatal
      exposure to testosterone has been suggested as one cause. In animals it has been
      shown that a female fetus located between two male ones is exposed to higher
      levels of testosterone. It is still unclear whether intra-uterine hormone
      transfer exists in humans. Therefore, the influence of an intra-uterine presence
      of a male co twin was studied in female fraternal twins (N=200). Women with a
      male co-twin outperformed women with a female co-twin by about a third standard
      deviation. In a no-twin control group (N=200), performance of women with a
      slightly older sibling did not depend upon the sibling's sex. These findings
      provide preliminary support for the theory of an influence of prenatal
      testosterone on mental rotation performance.

PMID- 21094202
TI  - Environmental triggers, genetic background, and Crohn's disease.

PMID- 21094203
TI  - Leukemia cells invading the liver express liver chemokine receptors and possess
      characteristics of leukemia stem cells in mice with MPD-like myeloid leukemia.
AB  - OBJECTIVE: Massive liver infiltration by leukemic cells is an indicator of poor
      prognosis in some hemoblastoses. The aim of this study was to determine the
      mechanism of liver invasion by leukemic cells using the mouse model of
      transplantable myeloproliferative disease-like myeloid leukemia characterized by
      liver invasion. MATERIALS AND METHODS: CD45+ cells from the liver of mice
      transplanted with leukemic cells were sorted by magnetic separation. Gene
      expression alterations in CD45+ cells invading the liver were examined by
      polymerase chain reaction arrays and quantitative real-time polymerase chain
      reaction (including polymerase chain reaction arrays) analysis of selected genes.
      RESULTS: Liver chemokine receptors (Ccr1, Ccr2, Ccr5, and others) were expressed
      in cells invading the liver. The expression level of Ccr1 was increased 149-fold
      in comparison with CD45+ cells derived from the livers of healthy mice.
      Expression levels of several genes responsible for proliferation and self-renewal
      were elevated dramatically, which is in accordance with a high concentration of
      leukemia stem cells in the livers of moribund animals. The nuclear factor-kappaB
      signaling pathway and several oncogenes are also activated in these leukemia
      cells. CONCLUSIONS: Overexpression of liver-specific cytokine receptors allowed
      the leukemic cells to invade the liver. The high concentration of leukemia stem
      cells in the liver suggests the cells of this leukemia are able to adapt to new
      extramedullar niches. The model for the investigation and development of
      preventative strategies against massive liver invasion are described here.

PMID- 21094204
TI  - Endo-immunology: interactions between the immune and endocrine systems.
      Introduction.

PMID- 21094205
TI  - ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor.
AB  - The mechanism by which extracellular ADP ribose (ADPr) increases intracellular
      free Ca(2+) concentration ([Ca(2+)](i)) remains unknown. We measured [Ca(2+)](i)
      changes in fura-2 loaded rat insulinoma INS-1E cells, and in primary beta-cells
      from rat and human. A phosphonate analogue of ADPr (PADPr) and 8-Bromo-ADPr (8Br
      ADPr) were synthesized. ADPr increased [Ca(2+)](i) in the form of a peak followed
      by a plateau dependent on extracellular Ca(2+). NAD(+), cADPr, PADPr, 8Br-ADPr or
      breakdown products of ADPr did not increase [Ca(2+)](i). The ADPr-induced
      [Ca(2+)](i) increase was not affected by inhibitors of TRPM2, but was abolished
      by thapsigargin and inhibited when phospholipase C and IP(3) receptors were
      inhibited. MRS 2179 and MRS 2279, specific inhibitors of the purinergic receptor
      P2Y1, completely blocked the ADPr-induced [Ca(2+)](i) increase. ADPr increased
      [Ca(2+)](i) in transfected human astrocytoma cells (1321N1) that express human
      P2Y1 receptors, but not in untransfected astrocytoma cells. We conclude that ADPr
      is a specific agonist of P2Y1 receptors.

PMID- 21094206
TI  - Genetics and genomics of childhood adrenocortical tumors.
AB  - Adrenocortical tumors in children are usually diagnosed because of signs of
      virilization and their prognosis is poor. They possess several distinct
      pathological features compared to adrenocortical tumors in adults and have an
      exceptional prevalence in southern Brazil, where they are nearly invariably
      linked to the presence of a germline specific TP53 (R337H) mutation. Other
      important factors in childhood adrenocortical tumor pathogenesis are
      overexpression of the Steroidogenic Factor-1 transcription factor and imprinting
      defects in the 11p15 genomic region, causing overexpression of Insulin-like
      Growth Factor-2. Genomic studies have revealed the prognostic relevance of the
      expression of some Major Histocompatibility Complex genes and the deregulation of
      the Insulin-like Growth Factor/mammalian Target Of Rapamycin pathway by microRNAs
      in these tumors. Our hope is that these findings will constitute the basis for
      the development of novel therapies that will be more active against these tumors
      and less toxic for the patients.

PMID- 21094207
TI  - Resveratrol reduces oxidative stress and cell death and increases mitochondrial
      antioxidants and XIAP in PC6.3-cells.
AB  - Resveratrol, a polyphenol derived e.g. from red grapes, has been shown to mediate
      several positive biological actions such as protection of cells against oxidative
      stress. It can also influence cell signaling, but the mechanisms behind its
      antioxidant properties are largely unknown. Here we show that RSV reduces
      oxidative stress and enhances cell survival in PC6.3 cells depending on the
      concentration. In these cells, RSV increased the levels of antioxidants, SOD2 and
      TRX2, and of X chromosome-linked inhibitor of apoptosis protein. RSV also
      activated NFkappaB signaling as shown using luciferase reporter constructs. These
      findings show that RSV regulates oxidative stress and mitochondrial antioxidants
      in neuronal cells. This may contribute to cell protection in various brain
      disorders.

PMID- 21094208
TI  - Different early ER-stress responses in the CLN8(mnd) mouse model of neuronal
      ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative
      disorders characterized by epilepsy, progressive motor and cognitive decline,
      blindness, and by the accumulation of autofluorescent lipopigment. Late-infantile
      onset forms (LINCL) include those linked to mutations in CLN8 gene, encoding a
      transmembrane protein at the endoplasmic reticulum (ER). In the motor neuron
      degeneration (mnd) mouse model of the CLN8-LINCL (CLN8(mnd)), we carried out an
      analysis of ER stress-related molecules in CNS structures that exhibit a variable
      rate of disease progression (early retinal degeneration and delayed brain and
      motoneuron dysfunction). At the presymptomatic state of 1-month-old CLN8(mnd)
      mice, we found an upregulation of GRP78 and activation of the transcription
      factor-6 (ATF6) in all structures examined, an activation of a CHOP-dependent
      pathway in the cerebellum, hippocampus and retina, a caspase-12-dependent pathway
      in the retina and no activation of these two pathways in the cerebral cortex and
      spinal cord. An increased CHOP expression was detected in the cortex and spinal
      cord at the early symptomatic state (4 months). Caspase-3 cleavage occurred
      presymptomatically in the cerebellum, hippocampus and retina, and symptomatically
      in the cerebral cortex and spinal cord. We also monitored activation of NF
      kappaB, which is engaged in the alarming phase of ER stress, together with
      increased levels of TRAF2, TNF-alpha and TNFR1, and no activation of ASK-1/JNK
      signalling pathway, all over mnd structures. The results suggest that early ER
      stress responses distinctly combined and ER-stress pathways integrated with
      inflammatory responses may contribute to the progression of the CLN8(mnd) disease
      in CNS structures.

PMID- 21094209
TI  - Cannabinoids attenuate cancer pain and proliferation in a mouse model.
AB  - We investigated the effects of cannabinoid receptor agonists on (1) oral cancer
      cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse
      cancer model. We utilized immunohistochemistry and Western blot to show that
      human oral cancer cells express CBr1 and CBr2. When treated with WIN55,212-2 (non
      selective), ACEA (CBr1-selective) or AM1241 (CBr2-selective) agonists in vitro,
      oral cancer cell proliferation was significantly attenuated in a dose-dependent
      manner. In vivo, systemic administration (0.013M) of WIN55,212-2, ACEA, or AM1241
      significantly attenuated cancer-induced mechanical allodynia. Tumor growth was
      also significantly attenuated with systemic AM1241 administration. Our findings
      suggest a direct role for cannabinoid mechanisms in oral cancer pain and
      proliferation. The systemic administration of cannabinoid receptor agonists may
      have important therapeutic implications wherein cannabinoid receptor agonists may
      reduce morbidity and mortality of oral cancer.

PMID- 21094210
TI  - Biochemical, neuropathological, and neuroimaging characteristics of early-onset
      Alzheimer's disease due to a novel PSEN1 mutation.
AB  - Familial Alzheimer's disease (AD) due to PSEN1 mutations provides an opportunity
      to examine AD biomarkers in persons in whom the diagnosis is certain. We describe
      a 55 year-old woman with clinically probable AD and a novel PSEN1 mutation who
      underwent genetic, clinical, biochemical and magnetic resonance and nuclear
      imaging assessments. We also describe neuropathological findings in her similarly
      affected brother. Neuropsychological testing confirmed deficits in memory,
      visuospatial and language function. CSF t-tau and p-tau181 were markedly elevated
      and Abeta(42) levels reduced. FDG-PET revealed hypometabolism in the left
      parietotemporal cortex. FDDNP-PET showed increased binding of tracer in medial
      temporal and parietal lobes and in the head of the caudate and anterior putamen
      bilaterally. Neuropathological examination of her brother showed the typical
      findings of AD and the striatum demonstrated amyloid pathology and marked
      neurofibrillary pathology beyond that typically seen in late-onset AD. A novel
      S212Y substitution in PSEN1 was present in the index patient and her affected
      brother but not in an older unaffected sister. An in vitro assay in which the
      S212Y mutation was introduced in cell culture confirmed that it was associated
      with increased production of Abeta(42). We describe biochemical, imaging, and
      neuropathological changes in a pedigree with a novel PSEN1 mutation. This allows
      us to validate the pathogenicity of this mutation and the indices used to assess
      AD.

PMID- 21094211
TI  - Muscarinic receptors within the ventromedial hypothalamic nuclei modulate
      metabolic rate during physical exercise.
AB  - The involvement of muscarinic cholinoceptors within the ventromedial hypothalamic
      nuclei (VMH) on the exercise-induced increase in oxygen consumption (VO(2)) was
      investigated. Rats were fitted with bilateral cannulae into the VMH for local
      delivery of drugs. On the day of the experiments, the animals were submitted to
      running exercise (20 m/min; 5% grade) until the point of fatigue. VO(2) was
      continuously measured after bilateral injections of either 0.2 MUL of 5 * 10(
      9)mol methylatropine or 0.15M NaCl solution into the VMH. Control experiments
      were conducted in freely moving rats on the treadmill. Muscarinic blockade within
      the VMH reduced time to fatigue by 32% and enhanced the increase in VO(2) from
      the 8th until the 17th min of exercise when compared to the control trial. In
      fact, time to fatigue was negatively correlated to the rate of increase in VO(2)
      (r(2)=0.747; P<0.001). However, bilateral injections of methylatropine in freely
      moving rats did not change VO(2) in comparison to saline injections. In
      conclusion, muscarinic cholinoceptors within the VMH are activated during
      exercise to modulate the increase in metabolic rate. Furthermore, blocking
      muscarinic transmission leads to a faster increase in VO(2) that is associated
      with the early interruption of exercise.

PMID- 21094212
TI  - WITHDRAWN: l-Arginine prevents the hypothalamic serotonin release but not the
      hypophagia induced by interleukin 1beta in normal Zucker rats.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 21094214
TI  - Expression profile of microRNAs in rat hippocampus following lithium-pilocarpine
      induced status epilepticus.
AB  - Although microRNAs are expressed extensively in the central nervous system in
      physiological and pathological conditions, their expression in neurological
      disorder of epilepsy has not been well characterized. Here we investigated
      microRNA expression pattern in post status epilepticus rats (24h after status).
      Rat MicroRNA array and differential analysis had detected 19 up-regulated
      microRNAs and 7 down-regulated microRNAs in rat hippocampus, and four randomly
      selected deregulated microRNAs (microRNA-34a, microRNA-22, microRNA-125a,
      microRNA-21) were confirmed by qRT-PCR, then their expression alterations in rat
      peripheral blood were analyzed. We found that these four deregulated microRNAs
      were also differentially expressed in rat peripheral blood, and trends for their
      blood expression alterations were just the same as their counterparts in rat
      hippocampus. Thus, our results have not only characterized the microRNA
      expression profile in post status epilepticus rat hippocampus but also
      demonstrated that some rat hippocampal microRNAs were probably associated with
      rat peripheral blood microRNAs. Moreover, targets of these deregulated microRNAs
      were analyzed using bioinformatics and the identified enriched MAPK pathway and
      long-term potentiation pathway might have been involved in molecular mechanisms
      concerning neuronal death, inflammation and epileptogenesis.

PMID- 21094213
TI  - Failure of NMDA receptor hypofunction to induce a pathological reduction in PV
      positive GABAergic cell markers.
AB  - Reduction in cortical presynaptic markers, notably parvalbumin (PV), for the
      chandelier subtype of inhibitory gamma-amino-butyric acid (GABA) interneurons is
      a highly replicated post-mortem finding in schizophrenia. Evidence from genetic
      and pharmacological studies implicates hypofunction of N-methyl-d-aspartate
      receptor (NMDAR)-mediated glutamatergic signaling as a critical component of the
      pathophysiology of schizophrenia. Serine racemase (SR) produces the endogenous
      NMDAR co-agonist d-serine, and disruption of the SR gene results in reduced NMDAR
      signaling. SR null mutant (-/-) mice were used to study the link between NMDAR
      hypofunction and decreased PV expression, assessed by immunoreactive (IR) cell
      density in the medial prefrontal cortex and hippocampus and protein levels in
      brain homogenates from the frontal cortex and hippocampus. Contrary to
      expectations, SR -/- mice showed modest elevations in PV-IR cell density and no
      difference in PV expression in brain homogenate. To control for these surprising
      results, we investigated PV expression in mice and rats following subchronic
      phencyclidine or ketamine treatments in adulthood. PV expression was not affected
      by drug these treatment in either species, failing to reproduce previously
      published findings. Our findings challenge the hypothesis that pathological
      deficits in PV expression are simply a consequence of NMDAR hypofunction.

PMID- 21094215
TI  - Enhancement of episodic memory in young and healthy adults: a paired-pulse TMS
      study on encoding and retrieval performance.
AB  - Transcranial magnetic stimulation (TMS) is a neurophysiological tool that can
      transiently influence brain excitability and improve cognitive performance.
      Facilitation effects induced by low frequency repetitive TMS on memory functions
      have been shown in a few studies in young and healthy participants [29] and in
      older individuals with memory complaints [40]. However, regions specifically
      involved in encoding and retrieval were not always systematically targeted. We
      thus aimed to facilitate episodic memory with online TMS systematically applied
      over the left or right dorsolateral prefrontal cortex (DLPFC) while participants
      were performing a recognition task. We applied online paired-pulse TMS (ppTMS)
      (15 ms inter-stimulus interval) either during encoding or retrieving of verbal or
      non-verbal material. Participants were 11 right-handed young individuals (21.33
      +/- 2.27 years old). Repeated measures ANOVA showed shorter reaction time when
      ppTMS are applied over the left DLPFC during encoding as compared to right
      homologous stimulation or to Sham condition. In contrast, ppTMS over the right
      DLPFC during retrieval was associated with shorter reaction times compared to
      left homologous stimulation. Overall, our data support for the first time that
      online ppTMS over the DLPFCs is capable of hastening memory processes in young
      and healthy individuals.

PMID- 21094216
TI  - Effect of the N-methyl-d-aspartate receptor antagonist on locomotor activity and
      cholecystokinin-induced anorexigenic action in a goldfish model.
AB  - We have previously identified that peripherally administered cholecystokinin
      (CCK) exerts an anorexigenic action via the vagal afferent, and subsequently the
      brain melanocortin- and corticotropin-releasing hormone-neuronal pathways in
      goldfish. N-Methyl-d-aspartate (NMDA) receptors have been shown to be involved in
      the regulations of locomotor activity and food intake in mammals. Although
      several neuropeptides and other factors exert similar effects in fish and
      mammals, the role of NMDA receptor in the control of locomotor activity and
      feeding behavior in fish is still unclear. In the present study, we examined the
      effect of the NMDA receptor antagonist, MK-801, on locomotor activity and food
      intake in the goldfish. Intraperitoneal (IP) injection of MK-801 at 0.15nmol/g
      body weight (BW) increased locomotor activity, but did not affect food
      consumption. IP injection of MK-801 at same dose attenuated peripheral CCK
      (100pmol/g BW)-induced anorexigenic, but not peripheral acyl ghrelin (10pmol/g
      BW)-induced orexigenic actions. These data show for the first time that the NMDA
      receptor-signaling pathway is involved in the regulation of locomotor activity
      and feeding behavior through modulation of the peripheral CCK-induced satiety
      signal, but not the orexigenic effect of ghrelin.

PMID- 21094217
TI  - Effect of pre- versus post-weaning environmental disturbances on social behaviour
      in mice.
AB  - Environmental factors are involved to various degrees in psychiatric diseases.
      Unfortunately, early-life manipulations have been rarely investigated in mice.
      Interestingly, given the advances in genetics, combination of environmental and
      genetic factors to get construct validity is now possible. Herein, spontaneous
      activity, anxiety-like behaviour, social behaviour and short term spatial working
      memory were assessed in mice after maternal separation or social isolation. Of
      note, social withdrawal was observed in both models suggesting that this aspect
      needs to be better considered in future studies, particularly in testing new
      treatments for schizophrenia.

PMID- 21094218
TI  - Simultaneously reduced NKCC1 and Na,K-ATPase expression in murine cochlear
      lateral wall contribute to conservation of endocochlear potential following a
      sensorineural hearing loss.
AB  - The mechanisms of the response in the murine cochlear lateral wall following
      sensorineural hearing loss (SNHL) are poorly understood. We focused on comparing
      the endocochlear potential (EP) with morphological changes in the lateral wall
      and expression of four important potassium (K(+)) transporters in a mouse model
      of SNHL induced by co-administration of aminoglycoside and loop diuretic. The
      expression of the alpha1 and alpha2 isoforms of Na,K-ATPase, Na-K-2Cl
      Cotransporter-1 (NKCC1) and potassium channel KCNQ1 was assessed. The EP showed a
      significant decline at 12h post-treatment followed by complete recovery by 2 days
      post-treatment. The EP was maintained at near normal levels in animals deafened
      for periods up to 112 days. Despite this recovery, there was a significant and
      progressive decrease in the thickness of the stria vascularis, which was
      predominantly due to atrophy of marginal cells. Both protein and mRNA expression
      of alpha1 and alpha2 isoforms of Na,K-ATPase and NKCC1 in the lateral wall were
      dramatically reduced following a long-term deafening. KCNQ1 expression remained
      unchanged. These observations provide insight into the detailed mechanisms of EP
      modulation following SNHL and may have crucial implications in the future
      treatment of aminoglycoside-induced hearing loss.

PMID- 21094219
TI  - Identification and characterization of a novel zebrafish semaphorin.
AB  - The semaphorin gene family contains numerous secreted and transmembrane proteins.
      Some of them function as the repulsive and attractive axon guidance molecules
      during development. Herein, we report the cloning and characterization of a novel
      member of zebrafish semaphorin gene, semaphorin 6E (sema6E). Sema6E is expressed
      predominantly in the nervous system during embryogenesis. Results also show that
      Sema6E binds Plexin-A1, but not other Plexins. Sema6E chemorepels not only dorsal
      root ganglion axons but also sympathetic axons. Therefore, Sema6E might utilize
      Plexin-A1 as a receptor to repel axons of the specific types during development.

PMID- 21094220
TI  - Lactate infusion at rest increases BDNF blood concentration in humans.
AB  - Studies in humans use blood lactate to determine the degree of the exercise
      intensity, suggesting that exercise with elevated blood lactate concentrations
      results in increased BDNF plasma concentrations. However, it is not clear if
      lactate per se or rather other mechanisms are responsible for changes in blood
      BDNF concentrations. The lactate clamp method at rest is an appropriate method to
      examine physiological responses of lactate on the human organism without the
      effects of exercise. Eight male sport students placed in a sitting position
      received intravenous infusions with a 4 molar sodium-lactate solution in an
      incremental design starting with an infusion rate of 0.01ml/kgBW/min for the
      first three minutes, which was increased every three minutes by 0.01ml/kgBW/min
      up to 0.08ml/kg/min in the 24th minute. All together each subject received
      4.2mmol of infusion. Venous blood samples were taken before and immediately after
      the infusion as well as in the 24th and the 60th min after the infusion period
      and analysed for BDNF. Blood gases and capillary blood lactate (La) were analysed
      before the test, every three minutes directly before increasing the infusion
      rate, at the end of the infusion and in the post infusions period until the 12th
      min and after 24 and 60min. BDNF and La increased significantly after the
      infusion and reached baseline values at the end of the experiment (p<0.05,
      p<0.01, respectively). pH and hydrogen ions increased from the beginning until
      the end of the infusion period (p<0.01). This data suggest that blood lactate is
      involved in the regulation of BDNF blood concentrations.

PMID- 21094221
TI  - Facilitating actions of an AMPA receptor potentiator upon extinction of
      contextually conditioned fear response in stressed mice.
AB  - Extinction of conditioned fear response is thought to be a biological process
      underlying exposure therapy for anxiety disorders. We have previously reported
      that an AMPA receptor potentiator, 4-[2-(phenylsulfonylamino)ethylthio]-2,6
      difluorophenoxyacetamide (PEPA), facilitates extinction of fear memory formed
      through contextual fear conditioning in mice that had never been exposed to
      experimental stress. On the other hand, recent findings suggest that the fear
      extinction is impaired in stressed rats or mice. The purpose of the present study
      was to examine whether PEPA facilitates impaired extinction of fear in stressed
      mice. For this purpose, mice were applied stress (a 2h restraint, a 20min forced
      swim, and ether inhalation), and contextual fear conditioning was carried out 7
      days later. After 1-3 days of conditioning, mice were re-exposed to the context
      for 6min, and behavioral freezing response was measured. The time mice spent
      frozen decreased following every extinction session, and the decrease was
      remarkably slower in the stressed mice than in control non-stressed mice. PEPA
      (3, 10, 30mg/kg body weight) or vehicle was intraperitoneally administered into
      stressed mice once before the first extinction session. The significant decrease
      of the freezing response in the extinction sessions was only seen in the 30mg/kg
      PEPA-administered stressed mice, compared with vehicle-administered stressed
      mice. A similar extent of decrease in the freezing response in the extinction
      sessions was observed in the PEPA-administered (30mg/kg) and d-cycloserine
      administered (30mg/kg) mice. These results suggest that PEPA facilitates
      extinction of contextual fear in stressed mice.

PMID- 21094223
TI  - Aging of the subventricular zone neural stem cell niche: evidence for quiescence
      associated changes between early and mid-adulthood.
AB  - Stem cells can exist in either active or quiescent states. In the aging
      hippocampus, adult neural stem cells (aNSCs) shift into a quiescent state,
      contributing to age-related reductions in hippocampal neurogenesis. Here, we
      focused on the subventricular zone (SVZ) stem cell niche of the adult forebrain,
      asking to what extent quiescence-associated changes in aNSCs are initiated
      between early and middle-age. Immunohistochemical and label retention experiments
      revealed that the overall output of the SVZ stem cell system was already highly
      decreased in middle-aged mice (12-months-old) compared with young adult mice (2
      month-old), as measured by reduced marker expression for multiple neural
      precursor sub-populations and diminished addition of SVZ-derived neuroblasts to
      the olfactory bulbs (OBs). These changes were associated with significant
      cytological aberrations within the SVZ niche, including an overall atrophy of the
      SVZ and accumulation of large lipid droplets within ependymal cells, which are
      key support cells of the SVZ niche. Importantly, the reduced output of the middle
      aged SVZ stem cell system correlated with quiescence-associated changes in middle
      aged aNSCs. Specifically, while tissue culture experiments showed that young
      adult and middle-aged forebrains possessed equal numbers of neurosphere-forming
      aNSCs, the middle-aged neurospheres exhibited differences in their in vitro
      properties, and middle-aged aNSCs in vivo divided less frequently. These findings
      demonstrate that aNSCs begin undergoing quiescence-associated changes between
      early and mid-adulthood in the mouse SVZ, and serve as a useful framework for
      further studies aimed at defining the early events involved in aging-associated
      quiescence of aNSCs.

PMID- 21094222
TI  - Different effects of zolpidem and diazepam on hippocampal sharp wave-ripple
      activity in vitro.
AB  - Sharp waves and the concurrent high-frequency "ripple" oscillation (100-200 Hz)
      is a prominent intrinsic hippocampal network activity that occurs during slow
      wave sleep and resting wakefulness with an important role in memory processes.
      Present data suggest that the generation of sharp wave-ripple (SWRs) requires a
      complex interaction between the various components of the hippocampal network
      with the important involvement of GABA(A) receptor (GABA(A)R)-mediated
      transmission. The positive modulators of GABA(A)Rs zolpidem and diazepam differ
      in their selectivity for the various subtypes of GABA(A)Rs. Only zolpidem
      preferentially binds to alpha1-containing receptors whereas diazepam, but not
      zolpidem, also activates alpha5-GABA(A)Rs. In this study using an in vitro model
      of SWRs we examined the hypothesis that the two drugs distinctly affect the
      various characteristics of SWRs. Remarkably, the two drugs displayed opposite
      effects on the ripple oscillation. Zolpidem enhanced whereas diazepam suppressed
      ripples. Furthermore diazepam, but not zolpidem, produced a temporal dissociation
      between ripples and sharp waves. Both drugs suppressed the generation of SWRs in
      the form of sequences of multiple events (i.e. clusters). It was also observed
      that at low concentrations both drugs increased the rate of initiation of
      episodes of SWR. At high concentration zolpidem but not diazepam continued to
      increase the rate of episodes of SWRs. We propose that an accurate yet dynamic
      balance between excitation and inhibition in specific sites of the hippocampal
      network distinctly regulates the generation of basic features of SWRs such as
      ripples and sequential activation of the neuronal assemblies which have
      particular functional roles.

PMID- 21094224
TI  - Melatonin inhibits tetraethylammonium-sensitive potassium channels of rod ON type
      bipolar cells via MT2 receptors in rat retina.
AB  - By challenging specific receptors, melatonin synthesized and released by
      photoreceptors regulates various physiological functions in the vertebrate
      retina. Here, we studied modulatory effects of melatonin on K+ currents of rod
      dominant ON type bipolar cells (Rod-ON-BCs) in rat retinal slices by patch-clamp
      techniques. Double immunofluorescence experiments conducted in isolated cell and
      retinal section preparations showed that the melatonin MT2 receptor was expressed
      in somata, dendrites and axon terminals of rat Rod-ON-BCs.
      Electrophysiologically, application of melatonin selectively inhibited the
      tetraethylammonium (TEA)-sensitive K+ current component, but did not show any
      effect on the 4-aminopyridine (4-AP)-sensitive component. Consistent with the
      immunocytochemical result, the melatonin effect was blocked by co-application of
      4-phenyl-2-propionamidotetralin (4-P-PDOT), a specific MT2 receptor antagonist.
      Neither protein kinase A (PKA) nor protein kinase G (PKG) seemed to be involved
      because both the PKA inhibitor Rp-cAMP and the PKG inhibitor KT5823 did not block
      the melatonin-induced suppression of the K+ currents. In contrast, application of
      the phospholipase C (PLC) inhibitor U73122 or the protein kinase C (PKC)
      inhibitor bisindolylmaleimide IV (Bis IV) eliminated the melatonin effect, and
      when the Ca2+ chelator BAPTA-containing pipette was used, melatonin failed to
      inhibit the K+ currents. These results suggest that suppression of the TEA
      sensitive K+ current component via activation of MT2 receptors expressed on rat
      Rod-ON-BCs may be mediated by a Ca2+-dependent PLC/inositol 1,4,5-trisphosphate
      (IP3/PKC signaling pathway.

PMID- 21094225
TI  - Identification and expression profiling of Ceratitis capitata genes coding for
      beta-hexosaminidases.
AB  - The goal of this study was to identify the genes coding for beta-N
      acetylhexosaminidases in the Mediterranean fruit fly (medfly) Ceratitis capitata,
      one of the most destructive agricultural pests, belonging to the Tephritidae
      family, order Diptera. Two dimeric beta-N-acetylhexosaminidases, HEXA and HEXB,
      have been recently identified on Drosophila sperm. These enzymes are involved in
      egg binding through interactions with complementary carbohydrates on the surface
      of the egg shell. Three genes, Hexosaminidase 1 (Hexo1), Hexosaminidase 2 (Hexo2)
      and fused lobes (fdl), encode for HEXA and HEXB subunits. The availability of C.
      capitata EST libraries derived from embryos and adult heads allowed us to
      identify three sequences homologous to the D. melanogaster Hexo1, Hexo2 and fdl
      genes. Here, we report the expression profile analysis of CcHexo1, CcHexo2 and
      Ccfdld in several tissues, organs and stages. Ccfdl expression was highest in
      heads of both sexes and in whole adult females. In the testis and ovary the three
      genes showed distinct spatial and temporal expression patterns. All the mRNAs
      were detectable in early stages of spermatogenesis; CcHexo2 and Ccfdl were also
      expressed in early elongating spermatid cysts. All three genes are expressed in
      the ovarian nurse cells. CcHexo1 and Ccfdl are stage specific, since they have
      been observed in stages 12 and 13 during oocyte growth, when programmed cell
      death occurs in nurse cells. The expression pattern of the three genes in medfly
      gonads suggests that, as their Drosophila counterparts, they may encode for
      proteins involved in gametogenesis and fertilization.

PMID- 21094226
TI  - Effects of diesel particulate matters on inflammatory responses in static and
      dynamic culture of human alveolar epithelial cells.
AB  - Diesel particulate matter (DPM) possesses the potential to induce acute and
      chronic health issues upon occupational and daily exposure. Many recent studies
      have focused on understanding molecular mechanisms to depict DPM's side effects
      inside the lung using static in vitro cell culture models. These studies have
      provided abundant fundamental information on DPM's adverse effects on cellular
      responses, but these systems were limited by the absence of dynamic nature to
      access relevant cellular responses and functionality. We hypothesized that the
      exposure of DPM under dynamic environment may affect the levels of cellular
      inflammation and reactive oxygen species, which may be different from those under
      static environments. In this study, we used the dynamic cell growth condition to
      mimic mechanically dynamic environment similar to the normal breathing in vivo.
      We also used high (20, 10, and 5 ppm) and low (3, 1, 0.1, and 0.01 ppm) ranges of
      DPM exposure to mimic different levels of exposure, respectively. Following 24-,
      48-, and 72-h exposure of DPM, Interleukin-8 (IL-8), C-reactive protein (CRP),
      reactive oxygen species (ROS), and total amount of protein were analyzed. Our
      results demonstrated the distinct differences in the profiles of inflammatory
      mediators (IL-8, CRP, and ROS) between the static and dynamic cell growth
      conditions.

PMID- 21094227
TI  - IL-4 mediates dicloxacillin-induced liver injury in mice.
AB  - Drug-induced liver injury (DILI) is a major problem in drug development and
      clinical drug therapy. In most cases, the mechanisms are still unknown. It is
      difficult to predict DILI in humans due to the lack of experimental animal
      models. Dicloxacillin, penicillinase-sensitive penicillin, rarely causes
      cholestatic or mixed liver injury, and there is some evidence for immunoallergic
      idiosyncratic reaction in human. In this study, we investigated the mechanisms of
      dicloxacillin-induced liver injury. Plasma ALT and total-bilirubin (T-Bil) levels
      were significantly increased in dicloxacillin-administered (600 mg/kg, i.p.)
      mice. Dicloxacillin administration induced Th2 (helper T cells)-mediated factors
      and increased the plasma interleukin (IL)-4 level. Neutralization of IL-4
      suppressed the hepatotoxicity of dicloxacillin, and recombinant mouse IL-4
      administration (0.5 or 2.0 MUg/mouse, i.p.) exacerbated it. Chemoattractant
      receptor-homologous molecule expressed on Th2 cells (CRTh2) is a cognate receptor
      for prostaglandin (PG) D(2), and is suggested to be involved in Th2-dependent
      allergic inflammation. We investigated the effect of 13,14-Dihydro-15-keto-PGD(2)
      (DK-PGD(2); 10 MUg/mouse, i.p.) administration on dicloxacillin-induced liver
      injury. DK-PGD(2)/dicloxacillin coadministration resulted in a significant
      increase of alanine aminotransferases and a remarkable increase of macrophage
      inflammatory protein 2 expression. In conclusion, to the best of our knowledge,
      this is the first report to demonstrate that dicloxacillin-induced liver injury
      is mediated by a Th2-type immune reaction and exacerbated by DK-PGD(2).

PMID- 21094228
TI  - Photosensitizer loaded HSA nanoparticles II: in vitro investigations.
AB  - The photosensitizing efficiency of human serum albumin (HSA) nanoparticles loaded
      with the photosensitizers meta-tetra(hydroxy-phenyl)-chlorin (mTHPC) and meta
      tetra(hydroxy-phenyl)-porphyrin (mTHPP) was investigated in vitro. The
      endocytotic intracellular uptake, and the time dependent drug release caused by
      nanoparticle decomposition of the PS loaded HSA nanoparticles were studied on
      Jurkat cells in suspension. The photoxicity as well as the intracellular singlet
      oxygen ((1)O(2)) generation were investigated in dependence on the incubation
      time. The obtained results show that HSA nanoparticles are promising carriers for
      the clinical used mTHPC (Foscan). After release the ((1)O(2)) generation as well
      as the phototoxicity are more efficient compared with mTHPC applied without the
      HSA nanoparticles.

PMID- 21094229
TI  - Monitoring of swelling of hydrophilic polymer matrix tablets by ultrasound
      techniques.
AB  - The aim of this study was to investigate the ability of ultrasound (US)
      techniques to monitor the swelling behaviour of hydrophilic polymer matrix
      tablets. Tablets were prepared from hydroxypropyl methylcellulose (HPMC) and
      polyethylene oxide (PEO) polymers. The movement of the eroding front was
      investigated with ultrasound scanning techniques on each tablet's outer interface
      during tablet immersion in phosphate buffer (PB). In addition, a US window
      technique was utilized to simultaneously evaluate eroding and swelling front
      movements during the tablet dissolution process. An optical monitoring was used
      as the reference method. The focused pulsed echo ultrasound method was found to
      be applicable for evaluating the swelling process of hydrophilic polymer matrix
      tablets. Furthermore, it was noted that the sensitivity to follow hydrogel
      formation and thickening by US monitoring varied depending on the polymer under
      study. Thus, multifront detection is challenging since the hydrogels formed by
      different polymers may have totally different acoustic properties. It was found
      that the microbubbles formed inside the hydrogel were acting as a "contrast
      agent", characteristic of some polymers during immersion. In spite of these
      challenges, the US window technique introduced in this study was proven to be a
      promising method for simultaneous multifront detection.

PMID- 21094230
TI  - Taste sensing systems (electronic tongues) for pharmaceutical applications.
AB  - Electronic tongues are sensor array systems able to detect single substances as
      well as complex mixtures by means of particular sensor membranes and
      electrochemical techniques. Two systems are already commercially available, the
      Insent taste sensing system and the alphaAstree electronic tongue. In addition,
      various laboratory prototype versions exist. Besides the successful use in food
      industry, the implementation for pharmaceutical purposes has strongly grown
      within the recent years. A reason for this is the increased interest of
      developing palatable formulations, especially for children. As taste assessment
      of drugs comes along with challenges due to possible toxicity and subjectivity of
      the taste assessors, electronic tongues could offer a safe and objective
      alternative. In order to provide guidance on the use of these systems, possible
      fields of interest are presented in this review, as for example, system
      qualification, quality control, formulation development, comparison between
      marketed drug products, and the validation of the methods used. Further,
      different approaches for solid and liquid dosage forms are summarized. But, also
      the difficulty to obtain absolute statements regarding taste was identified and
      the need of more validated data was discussed to offer guidance for the next
      years of research and application of electronic tongues for pharmaceutical
      applications.

PMID- 21094231
TI  - Dermal targeting of tacrolimus using colloidal carrier systems.
AB  - In the therapy of chronic inflammatory skin diseases, the epicutaneous
      application of anti-inflammatory drugs in combination with maintenance therapy
      leads to ideal therapeutic long term effects. In this work, the development of
      well-tolerated colloidal carrier systems (ME) containing tacrolimus is described.
      A comprehensive physico-chemical characterization of the novel systems was
      performed using different techniques. The potential of three ME compared to an
      ointment as suitable carrier for dermal delivery of tacrolimus was determined.
      The penetration studies demonstrated that in comparison to the standard vehicle
      ointment, all three ME resulted in higher concentrations of tacrolimus in the
      deeper skin layers independent of the time of incubation. Particularly, the
      percentage of the bioavailable amount of tacrolimus (sum of the amount found in
      the dermis and acceptor compartment) from the ME with concentrations up to 20.95
      +/- 12.03% after 1000 min incubation time differed significantly (p<0.01), when
      compared to the ointment which yielded a concentration of 6.41 +/- 0.57%. As a
      result of these experiments, using colloidal carrier systems, the penetration
      profile of tacrolimus was enhanced significantly (p<0.01). High drug amounts
      penetrated the target site in a short period of time after applying the ME.

PMID- 21094232
TI  - Preparation of new 5-fluorouracil-loaded zein nanoparticles for liver targeting.
AB  - This study proposes a new zein nanoparticle (ZP) encapsulated 5-fluorouracil (5
      FU) that target liver through intravenous delivery. The ZPs were prepared by
      phase separation process and optimized using uniform experimental design. The
      physical properties, in vitro drug release and stability of optimal drug-loaded
      ZPs were studied. The biodistribution and the target efficiency of the particles
      were investigated in a mouse model. The highest drug loading was obtained using
      zein: 5-FU, 3:1 (v/v); zein concentration, 12.5mg/ml, pH 9.18, mixing time, 3h
      and ethanol concentration, 40%. The encapsulation efficiency and the drug loading
      were 60.7 +/- 1.74 and 9.17 +/- 0.11 respectively. The size of ZPs and zeta
      potential were 114.9 +/- 59.4 nm and -45 +/- 0.3 mV respectively. Differential
      scanning calorimetry (DSC) demonstrated that the drug was encapsulated within the
      ZPs. A sustained release profile of 5-FU was observed from ZPs. The more stable
      storage condition of ZPs was at a temperature of 4  degrees C. In vivo, ZPs was
      mostly accumulated in liver following intravenous injection, and the targeting
      efficiency increased 31.33%. The relative uptake rate of liver was 2.79. Also,
      nano-sized ZPs were beneficial for prolonged blood residence (7.2-fold increase).
      These demonstrated that the drug-loaded ZPs could be efficiently targeted at the
      liver by intravenous delivery.

PMID- 21094233
TI  - Spray freeze drying with polyvinylpyrrolidone and sodium caprate for improved
      dissolution and oral bioavailability of oleanolic acid, a BCS Class IV compound.
AB  - Spray-freeze-drying (SFD) of oleanolic acid (OA), a BCS Class IV compound, with
      polyvinylpyrrolidone-40 (PVP-40) as stabilizer and sodium caprate (SC) as wetting
      agent and penetration enhancer produced kinetically stable, amorphous solid
      dispersion systems with superior in vitro dissolution performance, and better and
      more uniform absorption in comparison with commercial OA tablet. Relative to the
      SC-free formulation, the presence of SC in the formulation resulted in a
      significant increase in the in vivo absorption rate of OA while exerting no
      apparent impact on the extent of OA absorption. The SFD-processed OA formulations
      and commercial OA tablet generally exhibited large inter-animal variability in
      oral bioavailability, consistent with the absorption characteristics of BCS Class
      IV compounds. Inclusion of SC coupled with the replacement of OA with its sodium
      salt (OA-Na) in the formulation was shown to substantially decrease the observed
      absorption variability. Above results suggested that increases in both
      dissolution rate and intestinal permeability of BCS Class IV compounds, as
      exemplified by the SFD-processed dispersion system containing both OA-Na and SC,
      are critical to reducing the large inter-individual absorption variability
      commonly observed with this class of drugs.

PMID- 21094234
TI  - Release behaviour of clozapine matrix pellets based on percolation theory.
AB  - The release behaviour of clozapine matrix pellets was studied in order to
      investigate if it is possible to explain it applying the concepts of percolation
      theory, previously used in the understanding of the release process of inert and
      hydrophilic matrix tablets. Thirteen batches of pellets with different
      proportions of clozapine/microcrystalline cellulose (MCC)/hydroxypropylmethyl
      cellulose (HPMC) and different clozapine particle size fractions were prepared by
      extrusion-spheronisation and the release profiles were studied. It has been
      observed that the distance to the excipient (HPMC) percolation threshold is
      important to control the release rate. Furthermore, the drug percolation
      threshold has a big influence in these systems. Batches very close to the drug
      percolation threshold, show a clear effect of the drug particle size in the
      release rate. However, this effect is much less evident when there is a bigger
      distance to the drug percolation threshold, so the release behaviour of clozapine
      matrix pellets is possible to be explained based on the percolation theory.

PMID- 21094235
TI  - Design of a composite drug delivery system to prolong functionality of cell-based
      scaffolds.
AB  - Cell encapsulation technology raises hopes in medicine and biotechnology.
      However, despite important advances in the field in the past three decades,
      several challenges associated with the biocompatibility are still remaining. In
      the present study, the effect of a temporary release of an anti-inflammatory
      agent on co-administered encapsulated allogeneic cells was investigated. The aim
      was to determine the biocompatibility and efficacy of the approach to prevent the
      inflammatory response. A composite delivery system comprised of alginate-poly-l
      lysine-alginate (APA)-microencapsulated Epo-secreting myoblasts and dexamethasone
      (DXM)-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres was implanted
      in the subcutaneous space of Balb/c mice for 45 days. The use of independently co
      implanted DXM-loaded PLGA microspheres resulted in an improved functionality of
      the cell-based graft, evidenced by significantly higher hematocrit levels found
      in the cell-implanted groups by day 45, which was found to be more pronounced
      when higher cell-doses (100 MUL) were employed. Moreover, no major host reaction
      was observed upon implantation of the systems, showing good biocompatibility and
      capability to partially avoid the inflammatory response, probably due to the
      immunosuppressive effects related to DXM. The findings of this study imply that
      DXM-loaded PLGA microspheres show promise as release systems to enhance
      biocompatibility and offer advantage in the development of long-lasting and
      effective implantable microencapsulated cells by generating a potential
      immunopriviledged local environment and an effective method to limit the
      structural ensheathing layer caused by inflammation.

PMID- 21094236
TI  - Treatment of high fat diet induced type 2 diabetes in C57BL/6J mice by two
      medicinal plants used in traditional treatment of diabetes in the east of
      Algeria.
AB  - AIM OF THE STUDY: Hydro-alcoholic extracts of Centaurium erythraea Rafn (CE),
      Gentianaceae and Artemisia herba-alba Asso (AHA), Asteraceae, medicinal plants
      used in traditional treatment of diabetes in north-eastern Algeria, were tested
      in established type 2 diabetes induced with a standardized high fat diet (HFD) in
      mice. MATERIALS AND METHODS: After confirmation of diabetes (17th week), plant
      extracts were administered orally by gavage at a dose of 2 g/kg daily for 18
      weeks to male C57BL/6J mice fed HFD. Animals were weighed, food intake and plasma
      glucose measured weekly, insulin and lipid profile at study end. RESULTS: At 35
      weeks, groups treated with AHA or CE vs. HFD control had a significant reduction
      in mean (+/-SD) fasting blood glucose concentrations (143.8+/-23.9 and 139.5+/
      14.2 vs. 229.0+/-20.8 mg/dL, p<0.05, respectively), triglyceride (18.9+/-11.1 and
      16.0+/-6.5 vs. 62.8+/-18.3 mg/dL, p<0.05), total cholesterol (1.2+/-0.1 and 1.2+/
      0.3 vs. 1.8+/-1.1 g/L, p<0.05) and serum insulin concentrations (1.7+/-0.7 and
      0.9+/-0.7 vs. 3.3+/-14.3 ng/mL, p<0.05). Plant extracts also markedly reduced
      insulin resistance as compared to HFD controls (AHA: 15.6+/-9.1, CE: 9.0+/-7.7
      vs. HFD control 38.5+/-30.3, p<0.05). The plant extracts decreased calorie intake
      and had little effect on body weight or HDL-cholesterol. CONCLUSION: AHA has
      already been shown to have a antihyperglycaemic and antihyperlipidemic effect but
      this is the first demonstration of an effect of AHA and CE on established HFD
      induced diabetes.

PMID- 21094237
TI  - Antituberculosis potential of some ethnobotanically selected Malaysian plants.
AB  - AIM OF THE STUDY: Many local plants are used in Malaysian traditional medicine to
      treat respiratory diseases including symptoms of tuberculosis. The aim of the
      study was to screen 78 plant extracts from 70 Malaysian plant species used in
      traditional medicine to treat respiratory diseases including symptoms of
      tuberculosis for activity against Mycobacterium tuberculosis H37Rv using a
      colorimetric microplate-based assay. MATERIALS AND METHODS: Plant extracts were
      prepared by maceration in methanol (80%) and antituberculosis screening was
      carried out using Tetrazolium bromide microplate assay (TEMA) method to determine
      the minimum inhibitory concentration (MIC). RESULTS: Thirty-eight plant extracts
      from 36 plant species exhibited antituberculosis activity with MICs in the range
      of 1600-400 MUg/ml. The leaf extract of Angiopteris evecta exhibited the highest
      activity with MIC of 400 MUg/ml. Five other extracts, namely, Costus speciosus
      (stem and flower), Piper sarmentosum (whole plant), Pluchea indica (leaf),
      Pluchea indica (flower), and Tabernaemontana coronaria (leaf) exhibited
      antituberculosis activity, each with MIC of 800 MUg/ml. To the best of our
      knowledge, this is the first report of in vitro high throughput screening of
      Malaysian medicinal plants for antituberculosis activity. CONCLUSIONS:
      Antituberculosis activity of extracts of some plants justifies, to a certain
      extent their ethnomedicinal uses as remedies for symptoms of tuberculosis. These
      results also support the general view that, selecting the plants based on
      ethnobotanical criteria would enhance the probability of finding species with
      antituberculosis activity.

PMID- 21094238
TI  - TRAMIL ethnopharmalogical survey in Les Saintes (Guadeloupe, French West Indies):
      a comparative study.
AB  - AIM OF THE STUDY: The aim of this study was a comparison of popular household
      remedies in primary health care in the communities of Terre-de-Haut and Terre-de
      Bas, the inhabited islands of 'Les Saintes' archipelago (Guadeloupe, French West
      Indies). METHODS: Twelve ailments, with higher prevalence, were chosen in each
      island and a total of 216 families were interviewed using TRAMIL participative
      ethnopharmacological interviews. RESULTS: According to TRAMIL methodology
      (frequency over 20%), twenty-two plants uses were recorded for Terre-de-Haut and
      eighteen for Terre-de-Bas. The islands share only ten significant plants uses and
      four of them have notable different frequencies. The informant consensus factor
      in the use of many specific remedies was fairly high, that gave an additional
      validity to these popular medicines. CONCLUSION: The data presented in this study
      show that popular knowledge on medicinal plants uses is still alive in the
      studied area. The difference between the two nearby islands is very narrow but on
      the other hand, there exist some differences possibly due to a probable declining
      of plant resources and a more important flux of migration and its provision of
      other practices of healthcare in Terre-de-Haut.

PMID- 21094239
TI  - The potential role of female flowers inflorescence of Typha domingensis Pers. in
      wound management.
AB  - AIM OF THE STUDY: Female flowers inflorescence of Typha species including Typha
      domingensis Pers. are used externally for burns and wound healing in Turkish folk
      medicine. In order to verify the folkloric assertion, the female and male flowers
      inflorescences were individually submitted to in vivo wound models. MATERIAL AND
      METHODS: Ointment formulations prepared directly either from the male or female
      flowers inflorescences of Typha domingensis in 5% and 10% concentrations were
      submitted to activity testing. After that, female flowers inflorescence was
      further submitted to successive extractions with solvents in increasing polarity;
      i.e., n-hexane, chloroform, methanol and water and the wound healing activity of
      each extract was investigated. The linear incision and circular excision wound
      models were used for the evaluation of the healing potential of the test
      materials in rats and mice. Tissue sections were also evaluated by
      histopathological techniques. RESULTS: Remarkable wound healing activity was
      observed only for the female flowers inflorescence at 5% concentration in
      ointment base and its methanolic and aqueous extracts. The wound healing effect
      was found comparable to that of reference ointment Madecassol((r)). The results
      of histopathological evaluation supported the outcome of both linear incision and
      circular excision wound models. CONCLUSION: The experimental study revealed that
      the female flowers inflorescence of Typha domingensis displayed notable wound
      healing activity in mice and rats, at the models tested.

PMID- 21094240
TI  - Acute and chronic cannabinoid extracts administration affects motor function in a
      CREAE model of multiple sclerosis.
AB  - AIM OF THE STUDY: The multiple sclerosis is an immuno-mediated disorder of the
      Central Nervous System characterized by inflammatory processes and
      neurodegenerative changes. It has been shown that the endocannabinoid system is
      altered in this disease and that the exogenous cannabinoids may play a possible
      role in its therapeutic management. The aim of the present study was to
      investigate the efficacy of crude extracts of Cannabis sativa on motor symptoms
      in the chronic relapsing experimental autoimmune encephalomyelitis (CREAE), a
      murine model of multiple sclerosis. MATERIALS AND METHODS: CREAE-induced mice
      were injected by different crude ethanolic extracts from Cannabis sativa,
      containing Delta9-tetrahydrocannabinol, cannabidiol, or cannabinoid-free,
      respectively. The effect of the combined treatment with Delta9
      tetrahydrocannabinol and cannabidiol extracts has also been investigated. All
      extracts were administered in acute and chronic experimental protocols. RESULTS:
      The chronic administration of Delta9-tetrahydrocannabinol-rich extract resulted
      in a significant reduction of neurological deficits that lasted until the end of
      the observations. The acute and chronic treatments with the cannabidiol-rich
      extract resulted unable to induce changes of neurological signs. However, during
      the relapse phase a significant decrease of neurological scores was observed. The
      combined treatment with Delta9-tetrahydrocannabinol and cannabidiol extracts was
      ineffective, whereas the acute administration of the cannabinoid-free extract
      showed a significant improvement. CONCLUSIONS: Our study shows a patchy effect of
      different cannabinoid extracts on CREAE-induced motor deficits. Although the
      effect of crude extracts of Cannabis sativa here reported need to be further
      investigated to define the exact therapeutic target of each cannabinoid, it may
      represent a possible therapeutic approach for the management of the multiple
      sclerosis.

PMID- 21094241
TI  - Ethnobotanical survey of traditionally used plants in human therapy of east,
      north and north-east Bosnia and Herzegovina.
AB  - AIM OF THE STUDY: The study aims to provide a systematical revision of the
      traditional use of wild and cultivated plants in north-eastern Bosnia and
      Herzegovina (Western Balkan Peninsula; Southeast Europe). Thereby, it will extend
      and complement a recent previous study carried out in middle, southern and
      western Bosnia and Herzegovina. MATERIAL AND METHODS: Information was collected
      by performing so called open ethnobotanical interviews. The following data were
      recorded and systematically assembled in a database: name, age and occupation of
      the interviewed person; the geographic locality and date of the interview; the
      name of the used plant; plant parts used; prescription background and preparation
      procedure as well as indication. Plants mentioned to be used by the informants
      were collected during field trips done together with the informants and
      taxonomically determined. The corresponding material was finally deposited in the
      herbarium of the Department of Pharmacognosy of the University of Vienna for the
      purpose of documentation. RESULTS: In total, 45 places including villages and
      mountain areas were visited and 84 persons questioned. 254 wild and cultivated
      species and 1655 different preparations for the use in traditional human therapy
      were recorded. The most frequently mentioned indications were disorders of the
      gastrointestinal tract, respiratory system, urogenital tract, skin, blood system,
      cardiovascular system, nervous system as well as rheumatism. Infusions were the
      most frequently prepared formulation. Other applied preparations mentioned with
      decreasing frequency were decocts, sirups, tinctures, collars, direct application
      of plants without prior preparation, ointments, freshly pressed juices, oils,
      powders, fluid unctions, macerations and finally suppositories. Special
      preparations, typical only for the area of Bosnia and Herzegovina were "mehlems"
      and some kind of sirup called "dulbe secer" (eng. dulbe sugar). While "mehlems"
      were already recognized and accordingly discussed for the central, southern and
      western parts of Bosnia and Herzegovina, "dulbe secer" seems to be known in north
      eastern region only. The main compounds of this preparation are sugar or honey,
      lemon and flowers of one particular species of Rosa (with very small flowers), in
      Bosnia called "dulbe" rose or "sugar" rose. Prescriptions were verbally delivered
      for up to more than six generations, traditionally from mother to daughter. For
      the objective of further analyses and comparisons, the recorded data were
      inserted in the "VOLKSMED" data base of Austrian prescriptions. CONCLUSIONS: The
      study showed that there exist considerable similarities in medicinal plant use
      including indications and type of preparations between the different regions and
      ethnicities of Bosnia and Herzegovina. Interestingly, there were also only little
      differences in frequencies of medicinal plant use, indications and preparations
      between middle, western and southern part Bosnia and Herzegovina on one hand and
      the eastern, northern and north-eastern part of this county on the other hand.
      The results also demonstrated the high importance of medicinal plants for the
      physical health of Bosnian people. 70 of the species reported by Bosnian people
      were also used in official pharmacy. In addition, a variety of less known plants
      has been used since ages in traditional therapy of this country and hence may be
      potential sources for new therapies. Therefore, further pharmaceutical research
      into this particular and scientifically still underexplored proportion of Bosnian
      plant biodiversity appears promising and is recommended by the authors.

PMID- 21094242
TI  - Induction of insulin secretion by an aqueous extract of Tabernanhte iboga Baill.
      (Apocynaceae) in rat pancreatic islets of Langerhans.
AB  - The effect of an aqueous extract of Tabernanthe iboga (TBEt) was studied in the
      rat islets insulin secretion based on its use in traditional medicine for the
      treatment of diabetes. Rats islets were isolated by collagenase digestion. In
      insulin release experiments, the insulin content was determined by Enzyme-Link
      Immunosorbent Assay (ELISA). For experiments on 45Ca(2+) Uptake, the radioactive
      content was determined using a liquid scintillation analyzer. The extract (10-3
      MUg/ml-100 MUg/ml) did not exert a significant increase of insulin secretion
      (p>0.05) in the presence of 2.8 mM of glucose (a none stimulatory concentration).
      Whereas, in the presence of 11.1 mM of glucose (stimulatory concentration), TBEt
      augmented glucose-stimulated insulin secretion in a dose-dependent manner.
      Interestingly, the secretory effect of the extract was glucose-dependent (5.6
      16.7 mM). Furthermore, the insulinotropic effect of TBEt (1 MUg/ml) was
      significantly potentiated (p<0.001) in K(+)-depolarised media as well as in the
      presence of 2.8 mM and 16.8 mM of glucose concentrations. In contrast, in the
      same conditions, TBEt failed to stimulate the high K(+) medium-induced insulin
      release. The extract significantly amplified (p<0.001 and p<0.05) the insulin
      secretion induced by either IBMX or tolbutamide. Diazoxide, cobalt or calcium
      removal inhibited the insulinotropic effect of the extract. TBEt increased
      glucose-induced 45Ca(2+) uptake in rat islets. Overall, our findings suggest that
      Tabernanthe iboga contains water soluble insulinotropic compounds. The insulin
      secretion of TBEt's active principles might involve the closure of K(+)-ATP and
      the intensification of calcium influx through voltage-sensitive Ca(2+) channels.

PMID- 21094243
TI  - Standardized extract of Dicksonia sellowiana Presl. Hook (Dicksoniaceae)
      decreases oxidative damage in cultured endothelial cells and in rats.
AB  - AIMS: Aging and a variety of pathologies, including cancer, diabetes,
      cardiovascular and inflammatory diseases have been associated with reactive
      oxygen species (ROS), such as superoxide anion (O2.-), hydroxyl radical (.OH) and
      hydrogen peroxide (H2O2) generation. Plant polyphenols bear radical
      scavenging/antioxidant activity. A phytomedicinal preparation obtained from
      aerial parts of Dicksonia sellowiana (Dicksoniaceae), a native plant from Central
      and South America, has been widely used in Brazil against asthma and presents
      beneficial effects in several other diseases, including cardiovascular
      disturbance. In this work, we investigated whether Dicksonia sellowiana, which is
      also known to contain high levels of polyphenols, presents antioxidant activity.
      METHODS: The antioxidant activity of the hydroalcoholic extract obtained from
      Dicksonia sellowiana leaves (HEDS) was investigated by in vitro and in vivo
      tests. RESULTS: HEDS (0.1-100 MUg/mL) exhibited a strong scavenging activity
      against all reactive species tested (DPPH, O2.-,.OH and H2O2; IC50=6.83+/-2.05,
      11.6+/-5.4, 2.03+/-0.4, and 4.8+/-0.4 MUg/mL, respectively). HEDS strongly
      protected endothelial cells against H2O2-induced oxidative stress by mechanisms
      other than increasing catalase activity. In addition, HEDS protected cell
      membrane from oxidative damage. HEDS, (20 and 40 mg/kg) inhibited lipid
      peroxidation in vivo (29.8% and 24.5%, respectively). CONCLUSIONS: According to
      our results, we can speculate that the traditional uses of Dicksonia sellowiana
      for cardiovascular diseases, asthma and skin diseases could be, at least in part,
      related to the potent antioxidant and endothelial protective activities of the
      plant.

PMID- 21094244
TI  - Anti-inflammatory effect of ethyl acetate extract from Cissus quadrangularis Linn
      may be involved with induction of heme oxygenase-1 and suppression of NF-kappaB
      activation.
AB  - AIM OF THE STUDY: Cissus quadrangularis (family: Vitaceae) has been widely used
      in traditional herbal medicine for the treatment of hemorrhoids, gastric ulcers
      and bone healing. In the present study, we determined the anti-inflammatory
      activity and the molecular mechanism of the ethyl acetate extract of Cissus
      quadrangularis stem (CQE) in LPS-stimulated RAW 264.7 macrophage cells. MATERIALS
      AND METHODS: The inhibitory effect of CQE on LPS-induced nitric oxide (NO)
      production was evaluated in conditioned media. Cell viability was monitored by
      MTT assay. Protein and mRNA expressions were determined by RT-PCR and Western
      blotting analysis, respectively. RESULTS: CQE potently inhibited
      lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7
      macrophage cells in a dose-dependent manner. The mRNA and protein expressions of
      inducible nitric oxide synthase (iNOS) were suppressed also by CQE as was p65 NF
      kappaB nuclear translocation. Further study demonstrated that CQE by itself
      induced heme oxygenase-1 (HO-1) gene expression at the protein and mRNA levels in
      dose- and time-dependent manner. In addition, the inhibitory effects of CQE on NO
      production were abrogated by a HO-1 inhibitor, zinc protoporphyrin IX (ZnPP).
      CONCLUSIONS: Collectively, these results suggest that CQE exerts an anti
      inflammatory effect in macrophages, at least in part, through the induction of HO
      1 expression. These findings provide the scientific rationale for anti
      inflammatory therapeutic use of Cissus quadrangularis stem.

PMID- 21094245
TI  - Anti-inflammatory effect of Lithrea molleoides extracts and isolated active
      compounds.
AB  - AIM OF THE STUDY: In this study the anti-inflammatory activity of aqueous,
      dichloromethane (CH2Cl2) and methanolic (MeOH) extracts and two major compounds
      isolated from Lithrea molleoides (Vell.) Engl. (Anacardiaceae) were evaluated.
      MATERIALS AND METHODS: Two classical experimental models were used, carrageenan
      induced rat paw edema and 12-O-tetradecanoylphorbol-13 acetate (TPA) induced
      mouse ear edema. RESULTS: MeOH extracts exhibited a significant systemical anti
      inflammatory effect in the carrageenan (inhibition of 46% at 3 h) and in the TPA
      ear edema test (inhibition of 21%). The presence of methyl gallate (inhibition of
      63% in TPA ear edema), as one of the main compounds in the active fraction from
      MeOH extract may be explained the effect observed. Also, 1,3-dihydroxy-(Z,Z)-5
      (tridec-4',7dienyl) benzene obtained from CH2Cl2 extract showed a significant
      topical anti-inflammatory activity (inhibition of 68%). Furthermore, no signs of
      toxicity were observed with doses up to 3g/kg in an acute toxicity assay.
      CONCLUSIONS: The results of this study present evidence that Lithrea molleoides
      given either systemically or topically has anti-inflammatory properties.

PMID- 21094247
TI  - Genomic resources in horticultural crops: status, utility and challenges.
AB  - A significant review of status and availability of genomic resources in
      horticultural crops can be utilized for the efficient exploitation of the current
      research in developing improved varieties and also defining future goals. In this
      review, we describe the current genomic resources available in major
      horticultural crops and utility of the genomic and genic sequence information for
      isolating and characterizing novel useful genes and designing new DNA markers. We
      have found that these genomic resources have been utilized for both basic and
      applied research; however the progress is relatively slow. Recent advances in
      automation and high throughput techniques used in decoding plant genomes play an
      important role to speed up the genomic research. With the establishment of genome
      and transcriptome sequencing projects for several horticultural crops, huge
      wealth of sequence information have been generated. These sequence information
      have been used extensively for analyzing and understanding genome structures and
      complexities, comparative and functional genomics and to mine useful genes and
      molecular markers. However, certain limitations present a number of challenges
      for the generation and utilization of genomic resources in many important crops.

PMID- 21094248
TI  - Perspectives on microalgal CO2-emission mitigation systems--a review.
AB  - The problem of climate change arising mainly from CO2 emission is currently a
      critical environmental issue. Biofixation using microalgae has recently become an
      attractive approach to CO2 capture and recycling with additional benefits of
      downstream utilization and applications of the resulting microalgal biomass. This
      review summarizes the history and strategies of microalgal mitigation of CO2
      emissions, photobioreactor systems used to cultivate microalgae for CO2 fixation,
      current microalgae harvesting methods, as well as applications of valuable by
      products. It is of importance to select appropriate microalgal species to achieve
      an efficient and economically feasible CO2-emission mitigation process. The
      desired microalgae species should have a high growth rate, high CO2 fixation
      ability, low contamination risk, low operation cost, be easy to harvest and rich
      in valuable components in their biomass.

PMID- 21094246
TI  - Impairment of IGF-I expression and anabolic signaling following
      ischemia/reperfusion in skeletal muscle of old mice.
AB  - With the advancement of age, skeletal muscle undergoes a progressive decline in
      mass, function, and regenerative capacity. Previously, our laboratory has
      reported an age-reduction in recovery and local induction of IGF-I gene
      expression with age following tourniquet (TK)-induced skeletal muscle
      ischemia/reperfusion (I/R). In this study, young (6 mo) and old (24-28 mo) mice
      were subjected to 2h of TK-induced ischemia of the hindlimb followed by 1, 3, 5,
      or 7 days of reperfusion. Real time-PCR analysis revealed clear age-related
      reductions and temporal alterations in the expression of IGF-I and individual IGF
      I Ea and Eb splice variants. ELISA verified a reduction of IGF-I peptide with age
      following 7 day recovery from TK. Western blotting showed that the
      phosphorylation of Akt, mTOR, and FoxO3, all indicators of anabolic activity,
      were reduced in the muscles of old mice. These data indicate that an age-related
      impairment of IGF-I expression and intracellular signaling does exist following
      injury, and potentially has a role in the impaired recovery of skeletal muscle
      with age.

PMID- 21094249
TI  - Cytotoxicity of single-walled carbon nanotubes on PC12 cells.
AB  - The increasing use of carbon nanotubes (CNTs) in biomedical applications
      underlines the importance of its potential toxic effects to human health. In the
      present study, we first exposed PC12 cells, a commonly used in vitro model for
      neurotoxicity study, to two kinds of commercially available single-walled carbon
      nanotubes (SWCNTs), to investigate the effect of SWCNTs on nervous system in
      vitro. The decrease of PC12 cells viability was time and dose-dependent with
      exposure to SWCNTs demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release and
      morphological observation. Flow cytometry analysis showed that the PC12 cells'
      cycle was arrested in the G2/M phase, and their apoptotic rate induced by SWCNTs
      was dose-dependent. Further studies revealed SWCNTs decreased mitochondrial
      membrane potential (MMP), induced the formation of reactive oxygen species (ROS)
      and increased the level of lipid peroxide and decreased the activities of
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and
      the content of glutathione (GSH) in a time and dose-dependent manner. These
      findings reveal that SWCNTs may induce oxidative stress to nervous system in
      vivo, causing the occurrence of diseases related to cellular injuries of neuronal
      cells, such as neurodegenerative disorders, and demonstrating the necessity of
      further research in vivo.

PMID- 21094250
TI  - Two-generation reproductive toxicity study of aluminium sulfate in rats.
AB  - In a two-generation reproductive toxicity study, male and female rats were given
      aluminium sulfate (AS) in drinking water at 0, 120, 600 or 3000 ppm. AS reduced
      water consumption in all treatment groups, and body weight was transiently
      decreased in the 3000 ppm group. In the F1 and F2 pups, preweaning body weight
      gain was inhibited at 3000 ppm, and the liver and spleen weight was decreased at
      weaning. At this dose, vaginal opening was slightly delayed. There were no
      compound-related changes in other reproductive/developmental parameters,
      including developmental neurobehavioral endpoints. The data indicated that the
      NOAEL of AS in this two-generation study is 600 ppm for parental systemic
      toxicity and reproductive/developmental toxicity. The total ingested dose of
      aluminium from drinking water and food (standard rat diet, containing 25-29 ppm
      of aluminium) combined for this 600 ppm group was calculated to be 8.06 mg Al/kg
      bw/day.

PMID- 21094251
TI  - Neuroanatomical distribution and neurochemical characterization of cells
      expressing adenylyl cyclase isoforms in mouse and rat brain.
AB  - Transmembrane adenylyl cyclases (Adcy) are involved in the regulation of multiple
      brain processes such as synaptic plasticity, learning and memory. They synthesize
      intracellular cyclic adenosine monophosphate (cAMP) following activation by G
      protein coupled receptors. We examined the neuroanatomical distribution of the
      nine Adcy isoforms in rat and mouse brain by in situ hybridization, as well as
      their location in glutamatergic, GABAergic and cholinergic neurons in several
      mouse brain areas by double in situ hybridization. The Adcys are widely
      distributed throughout the brain in both rat and mouse, being especially abundant
      in cortex, hippocampus, thalamic nuclei, the olfactory system and the granular
      layer of the cerebellum. Double-labeling experiments showed that Adcy isoforms
      are differently expressed in glutamatergic, GABAergic and cholinergic neuronal
      cell populations. We report the neuroanatomical distribution of the nine known
      Adcy isoforms in rat and mouse brain and their cellular localization.

PMID- 21094252
TI  - Reduced DNA oxidation in aged prostaglandin H synthase-1 knockout mice.
AB  - Prostaglandin H synthase (PHS)-2 (COX-2) is implicated in the neurodegeneration
      of Alzheimer and Parkinson diseases. Multiple mechanisms may be involved,
      including PHS-catalyzed bioactivation of neurotransmitters, precursors, and
      metabolites to neurotoxic free radical intermediates. Herein, in vitro studies
      with the purified PHS-1 (COX-1) isoform and in vivo studies of aging PHS-1
      knockout mice were used to evaluate the potential neurodegenerative role of PHS-1
      catalyzed bioactivation of endogenous neurotransmitters to free radical
      intermediates that enhance reactive oxygen species formation and oxidative DNA
      damage. The brains of 2-year-old wild-type (+/+) PHS-1 normal and heterozygous
      (+/-) and homozygous (-/-) PHS-1 knockout mice were analyzed for 8-oxo-2'
      deoxyguanosine formation, characterized by high-performance liquid chromatography
      with electrochemical detection and by immunohistochemistry. Compared to aging PHS
      1(+/+) normal mice, aging PHS-1(-/-) knockout mice had less oxidative DNA damage
      in the cortex, hippocampus, cerebellum, and brain stem. This PHS-1-dependent
      oxidative damage was not observed in young mice. In vitro incubation of purified
      PHS-1 and 2'-deoxyguanosine with dopamine, L-DOPA, and epinephrine, but not
      glutamate or norepinephrine, enhanced oxidative DNA damage. These results suggest
      that PHS-1-dependent accumulation of oxidatively damaged macromolecules including
      DNA may contribute to the mechanisms and risk factors of aging-related
      neurodegeneration.

PMID- 21094253
TI  - Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation
      and ubiquitination.
AB  - Recent studies recognize that Hypocretin system (also known as Orexin) plays a
      critical role in sleep/wake disorders and feeding behaviors. However, little is
      known about the regulation of the Hypocretin system. It is also known that tumor
      necrosis factor alpha (TNF-alpha) is involved in the regulation of sleep/wake
      cycle. Here, we test our hypothesis that the Hypocretin system is regulated by
      TNF-alpha. Prepro-Hypocretin and Hypocretin receptor 2 (HcrtR2) can be detected
      at a very low level in rat B35 neuroblastoma cells. In response to TNF-alpha,
      Prepro-Hypocretin mRNA and protein levels are down-regulated, and also HcrtR2
      protein level is down-regulated in B35 cells. To investigate the mechanism,
      exogenous rat Prepro-Hypocretin and rat HcrtR2 were overexpressed in B35 cells.
      In response to TNF-alpha, protein and mRNA of Prepro-Hypocretin are significantly
      decreased (by 93% and 94%, respectively), and the half-life of Prepro-Hypocretin
      mRNA is decreased in a time- and dose-dependent manner. The level of HcrtR2 mRNA
      level is not affected by TNF-alpha treatment; however, HcrtR2 protein level is
      significantly decreased (by 86%) through ubiquitination in B35 cells treated with
      TNF-alpha. Downregulation of cellular inhibitor of apoptosis protein-1 and -2
      (cIAP-1 and -2) abrogates the HcrtR2 ubiquitination induced by TNF-alpha. The
      control green fluorescent protein (GFP) expression is not affected by TNF-alpha
      treatment. These studies demonstrate that TNF-alpha can impair the function of
      the Hypocretin system by reducing the levels of both Prepro-Hypocretin and
      HcrtR2.

PMID- 21094254
TI  - Relevance of equivalence assessment of topical products based on the
      dermatopharmacokinetics approach.
AB  - Common procedures to test bioequivalence of oral products, measuring the rate and
      extent of the obtained plasma levels, do not apply to drug products for topical
      use, which provide limited systemic absorption. Nowadays, clinical trials are
      still the goldenrule for the development of a generic topical product but,
      unfortunately, not many techniques are helpful for the specific investigation of
      in vivo topical absorption. Additionally, during early stages of pharmaceutical
      development, experimental procedures for demonstrating the quality by design of
      topical formulations are lacking. In some cases, the dermatopharmacokinetic
      characterization in healthy volunteers of the topical drug penetration by skin
      stripping has resulted to be a promising option. Recently, some authors have
      focused special efforts to enlighten all the capabilities of this approach. This
      short review tries to describe and discuss some aspects under optimization of
      dermatopharmacokinetics as is the influence of the formulation on drug
      performance, the parameter calculation and the experimental procedure for
      minimizing variability. All those aspects are nowadays in continuous improvement
      trying to define the place of dermatopharmacokinetics as a putative technique for
      avoiding clinical trials in topical generics development.

PMID- 21094255
TI  - A review of mechanistic studies on aromatase (CYP19) and 17alpha-hydroxylase
      17,20-lyase (CYP17).
AB  - In the conventional P-450 dependent hydroxylation reaction, the Fe(III) resting
      state of the enzyme, by a single electron transfer, is reduced to Fe(II), which
      reacts with O(2) to produce a Fe(III)-O-O intermediate. The latter following the
      transfer of another electron furnishes a ferric-peroxyanion, Fe(III)-O-O(-),
      which after protonation leads to the fission of the O-O bond resulting in the
      formation of Fe(V)O, the key player in the hydroxylation process. Certain members
      of the P-450 family, including CYP17 and CYP19, catalyze, at the same active
      site, not only the hydroxylation process but also an acyl-carbon bond cleavage
      reaction which has been interpreted to involve the nucleophilic attack of the
      ferric-peroxyanion, Fe(III)-O-O(-), on the acyl carbon to furnish a tetrahedral
      intermediate which fragments, leading to acyl-carbon cleavage. Evidence is
      presented to show that in the case of CYP17 the attack of Fe(III)-O-O(-) on the
      target carbon is promoted by cytochrome b(5), which acts as a conformational
      regulator of CYP17. It is this regulation of CYP17 that provides a safety
      mechanism which ensures that during corticoid biosynthesis, which involves
      17alpha-hydroxylation by CYP17, androgen formation is avoided. Finally, a brief
      account is presented of the inhibitors, of the two enzymes, which have been
      designed on the basis of their mechanism of action. Article from the Special
      issue on 'Targeted Inhibitors'.

PMID- 21094256
TI  - TRPA1 is activated by direct addition of cysteine residues to the N
      hydroxysuccinyl esters of acrylic and cinnamic acids.
AB  - The nociceptor TRPA1 is thought to be activated through covalent modification of
      specific cysteine residues on the N terminal of the channel. The precise
      mechanism of covalent modification with unsaturated carbonyl-containing compounds
      is unclear, therefore by examining a range of compounds which can undergo both
      conjugate and/or direct addition reactions we sought to further elucidate the
      mechanism(s) whereby TRPA1 can be activated by covalent modification. Calcium
      signalling was used to determine the mechanism of activation of TRPA1 expressed
      in HEK293 cells with a series of related compounds which were capable of either
      direct and/or conjugate addition processes. These results were confirmed using
      physiological recordings with isolated vagus nerve preparations. We found
      negligible channel activation with chemicals which could only react with cysteine
      residues via conjugate addition such as acrylamide, acrylic acid, and cinnamic
      acid. Compounds able to react via either conjugate or direct addition, such as
      acrolein, methyl vinyl ketone, mesityl oxide, acrylic acid NHS ester,
      cinnamaldehyde and cinnamic acid NHS ester, activated TRPA1 in a concentration
      dependent manner as did compounds only capable of direct addition, namely
      propionic acid NHS ester and hydrocinnamic acid NHS ester. These compounds failed
      to activate TRPV1 expressed in HEK293 cells or mock transfected HEK293 cells. For
      molecules capable of direct or conjugate additions, the results suggest for the
      first time that TRPA1 may be activated preferentially by direct addition of the
      thiol group of TRPA1 cysteines to the agonist carbonyl carbon of alpha,beta
      unsaturated carbonyl-containing compounds.

PMID- 21094257
TI  - Structural basis of triclosan resistance.
AB  - Triclosan (5-chloro-2-(2,4-dichloro-phenoxy)-phenol, TCL) is a well known
      inhibitor against enoyl-acyl carrier protein reductase (ENR), an enzyme critical
      for cell-wall synthesis of bacteria. The inhibitory concentration at 50%
      inhibition (IC(50)) of TCL against the Escherichia coli ENR is 150nM for wild
      type (WT), 380, 470 and 68,500nM for Ala, Ser and Val mutants, respectively. To
      understand this high TCL resistance in the G93V mutant, we obtained the crystal
      structures of mutated ENRs complexed with TCL and NAD(+). The X-ray structural
      analysis along with the ab initio calculations and molecular dynamics simulations
      explains the serious consequence in the G93V mutant complex. The major
      interactions around TCL due to the aromatic(cation)-aromatic and hydrogen bonding
      interactions are found to be conserved both in WT and mutant complexes. Thus, the
      overall structural change of protein is minimal except that a flexible alpha
      helical turn around TCL is slightly pushed away due to the presence of the bulky
      valine group. However, TCL shows substantial edge-to-face aromatic (pi)
      interactions with both the flexible R192-F203 region and the residues in the
      close vicinity of G93. The weakening of some edge-to-face aromatic interactions
      around TCL in the G93V mutant results in serious resistance to TCL. This
      understanding is beneficial to design new generation of antibiotics which will
      effectively act on the mutant ENRs.

PMID- 21094258
TI  - TDCS guided using fMRI significantly accelerates learning to identify concealed
      objects.
AB  - The accurate identification of obscured and concealed objects in complex
      environments was an important skill required for survival during human evolution,
      and is required today for many forms of expertise. Here we used transcranial
      direct current stimulation (tDCS) guided using neuroimaging to increase learning
      rate in a novel, minimally guided discovery-learning paradigm. Ninety-six
      subjects identified threat-related objects concealed in naturalistic virtual
      surroundings used in real-world training. A variety of brain networks were found
      using functional magnetic resonance imaging (fMRI) data collected at different
      stages of learning, with two of these networks focused in right inferior frontal
      and right parietal cortex. Anodal 2.0 mA tDCS performed for 30 min over these
      regions in a series of single-blind, randomized studies resulted in significant
      improvements in learning and performance compared with 0.1 mA tDCS. This
      difference in performance increased to a factor of two after a one-hour delay. A
      dose-response effect of current strength on learning was also found. Taken
      together, these brain imaging and stimulation studies suggest that right frontal
      and parietal cortex are involved in learning to identify concealed objects in
      naturalistic surroundings. Furthermore, they suggest that the application of
      anodal tDCS over these regions can greatly increase learning, resulting in one of
      the largest effects on learning yet reported. The methods developed here may be
      useful to decrease the time required to attain expertise in a variety of
      settings.

PMID- 21094260
TI  - Projecting out muscle artifacts from TMS-evoked EEG.
AB  - Transcranial magnetic stimulation combined with electroencephalography is a
      powerful tool for probing cortical excitability and connectivity; we can perturb
      one brain area and study the reactions at the stimulated and interconnected
      sites. When stimulating areas near cranial muscles, their activation produces a
      large artifact in the electroencephalographic signal, lasting tens of
      milliseconds and masking the early brain signals. We present an artifact removal
      method based on projecting out the topographic patterns of the muscle activity.
      Although the brain and muscle components overlap both temporally and spectrally,
      the fact that muscle activity is present also at frequencies higher than 100 Hz,
      while brain signal is mostly restricted to frequencies lower than that, allows us
      to study the high-frequency muscle activity without brain contribution. We
      determined the muscle activity topographies from data highpass-filtered at a 100
      Hz cutoff frequency using principal component analysis. Projecting out the
      topographies of the principal components which explain most of the variance of
      the high-frequency data reduces not only the high-frequency activity but also the
      low-frequency muscle contribution, because the topography produced by a muscle
      source can be expected to be the same regardless of the frequency. The method
      greatly reduced the muscle artifact evoked by stimulation of Broca's area, while
      a significant brain signal contribution remained. Improvement in the signal-to
      artifact ratio, defined as the relative amplitudes of brain signals peaking after
      50 ms and the first artifact deflection, was of the order of 10-100 depending on
      the number of projections. The presented artifact removal method enables one to
      study the cortical state when stimulating areas near the cranial muscles.

PMID- 21094259
TI  - Medial prefrontal cortex predicts and evaluates the timing of action outcomes.
AB  - The medial prefrontal cortex (mPFC) is active in conditions of performance
      monitoring including error commission and response conflict, but the mechanisms
      underlying these effects remain in dispute. Recent work suggests that mPFC learns
      to predict the value of actions, and that error effects represent a discrepancy
      between actual and expected outcomes of an action. In general, expectation
      signals regarding the outcome of an action may have a temporal structure, given
      that outcomes are expected at specific times. Nonetheless, it is unknown whether
      and how mPFC predicts the timing as well as the valence of expected action
      outcomes. Here we show with fMRI that otherwise correct feedback elicits apparent
      error-related activity in mPFC when delivered later than expected, suggesting
      that mPFC predicts not only the valence but also the timing of expected outcomes
      of an action. Results of a model-based analysis of fMRI data suggested that
      regions in the caudal cingulate zone, dorsal mPFC, and dorsal anterior cingulate
      cortex were jointly responsive to unexpectedly delayed feedback and negative
      feedback outcomes. These results suggest that regions in anterior cingulate and
      mPFC may be more broadly responsive to outcome prediction errors, signaling
      violations of both predicted outcome valence and predicted outcome timing, and
      the results further constrain theories of performance monitoring and cognitive
      control pertaining to these regions.

PMID- 21094262
TI  - Multimodal imaging demonstrates concomitant changes in bone and cartilage after
      destabilisation of the medial meniscus and increased joint laxity.
AB  - OBJECTIVE: Alterations in joint mechanics can cause osteoarthritis, which results
      in degeneration of both cartilage and bone tissue. The objective of this work is
      to measure changes in the laxity of the mouse knee joint after destabilisation of
      the medial meniscus (DMM) and to visualise and quantify the resulting three
      dimensional changes in the bone and cartilage. METHODS: Skeletally mature C57Bl6
      male mice underwent DMM surgery in the right leg. Animals were sacrificed
      immediately 0 weeks (n=15), 4 weeks (n=11) or 8 weeks (n=12) after surgery. For
      the 0-week group, the anterior-posterior (AP) and varus-valgus laxity of the DMM
      limb were compared to the contralateral limb. For 4 and 8-week groups, tibiae
      were scanned with micro-computed tomography (MUCT) to quantify and visualise bone
      changes and with confocal scanning laser microscopy (CSLM) to measure changes in
      cartilage. RESULTS: Laxity testing measured an increase in AP range of motion,
      particularly in the anterior direction. The DMM limbs showed a decrease in
      epiphyseal trabecular bone at 8 weeks and a decrease in cartilage volume,
      primarily on the posterior medial plateau, compared to the contralateral limb.
      Significant bone remodelling was observed at the periphery of the joint and in
      severe cases, osteolysis extended through the growth plate. CONCLUSION:
      Multimodal imaging allowed quantifiable 3D assessment of bone and cartilage and
      indicated extensive changes in the tissues. The increase in AP laxity suggests
      that DMM surgery redistributes loading posteriorly on the medial plateau,
      resulting in bone and cartilage loss primarily on the posterior portion of the
      medial plateau.

PMID- 21094261
TI  - Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2
      transcriptional factor in SW1353 chondrocyte-like cells.
AB  - OBJECTIVE: To investigate the mechanism of mechanical stress-induced expression
      and regulation of aggrecanases and examine the role of runt-related transcription
      factor 2 (RUNX-2) in chondrocyte-like cells. METHODS: SW1353 cells were seeded
      onto stretch chambers at a concentration of 5*104 cells/chamber, and a uni-axial
      cyclic tensile strain (CTS) (0.5 Hz, 10% stretch) was applied for 30 min. Total
      RNA was extracted, reverse transcribed, and analyzed by polymerase chain reaction
      (PCR) and real-time PCR. RUNX-2 overexpression and small interfering RNA (siRNA)
      targeting RUNX-2 were used to investigate the role of RUNX-2 in CTS-induced gene
      expression. The involvement of diverse mitogen-activated protein kinase (MAPK)
      pathways in the activation of RUNX-2, MMP-13 and ADAMTS-5 during CTS was examined
      by Western blotting. RESULTS: CTS induced expression of RUNX-2, MMP-13, ADAMTS-4,
      -5, and -9. Overexpression of RUNX-2 up-regulated expression of MMP-13 and ADAMTS
      5, whereas RUNX-2 siRNA resulted in significant down-regulation of mechanically
      induced MMP-13 and ADAMTS-5 expression. CTS induced activation of p38 MAPK, and
      CTS induction of RUNX-2, MMP-13 and ADAMTS-5 mRNA was down-regulated by the
      selective p38 MAPK inhibitor SB203580 but not by the p44/42 MAPK inhibitor U0126,
      or the JNK MAPK inhibitor JNK inhibitor II. CONCLUSIONS: RUNX-2 might have a role
      as a key downstream mediator of p38's ability to regulate mechanical stress
      induced MMP-13 and ADAMTS-5 expression.

PMID- 21094263
TI  - Expression of the naphthoate synthase gene in Mycobacterium tuberculosis in a
      self-generated oxygen depleted liquid culture system.
AB  - Mycobacterium tuberculosis has been classified for decades as a strict aerobic
      species. Whole genome sequencing of the type culture strain H37Rv has revealed
      the presence of a full set of genes allowing for anaerobic metabolism. Naphthoate
      synthase (menB) is a key enzyme required for the synthesis of menaquinone, which
      plays a crucial role in anaerobic electron transport, ultimately resulting in the
      formation of energy generating intermediates. Interrupting the synthesis of this
      enzyme will interfere with the production of menaquinone and therefore this
      enzyme is a potential drug target. This study serves to investigate the role of
      naphtoate synthase in the survival of M. tuberculosis H37Rv when incubated under
      oxygen limiting conditions of unagitated liquid culture over 15 weeks. M.
      tuberculosis H37Rv was grown in Middlebrook 7H9 media. The tubes were kept
      undisturbed at 37  degrees C for up to 15 weeks. At selected time points,
      aliquots of cells were removed and frozen. RNA was simultaneously extracted from
      all aliquots. The RNA was converted to cDNA for Real-Time PCR on the ABI 7000
      SDS. Gene expression was normalized against 16S RNA quantities at each time
      point. A systematic increase in the expression of the menB gene product was
      observed over the incubation period with a 4.3-fold increase seen at week 6 (P <
      0.001) relative to day 0 and an 85.8-fold increase at week 15 (P < 0.001)
      relative to day 0. Cells of M. tuberculosis increase menaquinone production
      during prolonged incubation in broth culture as a mechanism of survival. This
      study substantiates the menB enzyme to be a putative drug target.

PMID- 21094264
TI  - Genome-wide inventory of metal homeostasis-related gene products including a
      functional phytochelatin synthase in the hypogeous mycorrhizal fungus Tuber
      melanosporum.
AB  - Ectomycorrhizal fungi are thought to enhance mineral nutrition of their host
      plants and to confer increased tolerance toward toxic metals. However, a global
      view of metal homeostasis-related genes and pathways in these organisms is still
      lacking. Building upon the genome sequence of Tuber melanosporum and on
      transcriptome analyses, we set out to systematically identify metal homeostasis
      related genes in this plant-symbiotic ascomycete. Candidate gene products (101)
      were subdivided into three major functional classes: (i) metal transport (58);
      (ii) oxidative stress defence (32); (iii) metal detoxification (11). The latter
      class includes a small-size metallothionein (TmelMT) that was functionally
      validated in yeast, and phytochelatin synthase (TmelPCS), the first enzyme of
      this kind to be described in filamentous ascomycetes. Recombinant TmelPCS was
      shown to support GSH-dependent, metal-activated phytochelatin synthesis in vitro
      and to afford increased Cd/Cu tolerance to metal hypersensitive yeast strains.
      Metal transporters, especially those related to Cu and Zn trafficking, displayed
      the highest expression levels in mycorrhizae, suggesting extensive translocation
      of both metals to root cells as well as to fungal metalloenzymes (e.g., laccase)
      that are strongly upregulated in symbiotic hyphae.

PMID- 21094265
TI  - Autophagy-related lipase FgATG15 of Fusarium graminearum is important for lipid
      turnover and plant infection.
AB  - Autophagy is a non-selective degradation pathway in eukaryotic cells that is
      conserved from yeasts to humans. Autophagy is involved in the virulence of
      several pathogenic fungi such as Magnaporthe grisea or Colletotrichum orbiculare.
      In the current study, we identified and disrupted an autophagy-like lipase
      FgATG15 in Fusarium graminearum. We showed that FgATG15 exhibits lipase activity
      when heterologously expressed in P. pastoris. We used a gene deletion approach to
      characterize the function of the enzyme. We demonstrate that FgATG15 is involved
      in fungal growth and aerial hyphae production. FgATG15 is also involved in
      conidia production and germination, and disruption of FgATG15 led to aberrant
      conidia shapes. FgATG15 disruptants were reduced in storage lipid degradation
      under starvation conditions, implicating FgATG15's involvement in lipid turnover.
      Moreover, wheat head infection by the disruptants was severely attenuated,
      indicating the involvement of FgATG15 in pathogenesis. Additionally, we found
      that the deoxynivalenol levels of FgATG15 disruptants were significantly
      decreased compared with the wild type strain. Taken together, we show that
      FgATG15 is involved in numerous developmental processes and could be exploited as
      an antifungal target.

PMID- 21094266
TI  - Nitric oxide regulates the repair of injured skeletal muscle.
AB  - Skeletal muscle repair can be understood as a balance between fibrosis and
      regeneration, the result of which may lead to complete recovery or loss of muscle
      function. To study the involvement of nitric oxide in post-trauma muscle repair,
      we used an experimental murine model of crush injury muscle. The animals were
      divided into four groups, (i) control (CO), (ii) sham trauma, (iii) trauma and
      (iv) trauma+l-NAME. The animals received a single dose of 100mg/kg of the l-NAME,
      an inhibitor of nitric oxide synthase, 2h after lesion, and the muscle tissue was
      analyzed in two time-points: 24h and 7 days. Twenty-four hours after injury, the
      crushed muscle was characterized by an intense inflammatory cell infiltrate and
      edema demonstrated by histological analysis. These changes were accompanied by
      increased iNOS, MMP-2 and HGF mRNA transcription and protein expression of the
      iNOS and MMP-2 in the gastrocnemius muscle. Crushing injury also promoted cell
      proliferation and increase number satellite cell, responsible for the
      regeneration of the muscle fiber. Treatment with l-NAME blocking local NO
      production, greatly attenuated these histological and molecular findings at 24h.
      On the 7th day the molecular findings of both groups were comparable to the
      control (sham trauma) group. However, the l-NAME group showed increase deposition
      of collagen and decrease of SC expression. These findings demonstrate that
      activation of NO during muscle crush is critical in the early phases of the
      skeletal muscle repair process and indicate its possible role as a regulator of
      the balance between fibrosis and muscle regeneration.

PMID- 21094268
TI  - Effectiveness of the Q fever vaccine: a meta-analysis.
AB  - In the Netherlands, the number of notified human Q fever cases showed a steep
      increase over the last three years and is not expected to disappear in the next
      few years. Since vaccination might be an option to prevent Q fever cases in the
      general population, evidence is needed about its effectiveness. We therefore
      conducted a meta-analysis to determine the evidence base for effectiveness for Q
      fever vaccination in human populations. We calculated Mantel-Haenszel risk ratios
      and we used the following formula to calculate the vaccines effectiveness: (1
      mhRR) * 100%. Although individual and the pooled estimates showed a high
      effectiveness of Q fever vaccine, conclusions for the general population cannot
      be confidently drawn about vaccine effectiveness due to potential flaws in the
      design of the studies and the selected group of study participants.

PMID- 21094267
TI  - Cardioprotective effects of hydrogen sulfide.
AB  - The gaseous mediator hydrogen sulfide (H(2)S) is synthesized mainly by
      cystathionine gamma-lyase in the heart and plays a role in the regulation of
      cardiovascular homeostasis. Here we first overview the state of the art in the
      literature on the cardioprotective effects of H(2)S in various models of cardiac
      injury. Subsequently, we present original data showing the beneficial effects of
      parenteral administration of a donor of H(2)S on myocardial and endothelial
      function during reperfusion in a canine experimental model of cardiopulmonary
      bypass. Overview of the literature demonstrates that various formulations of
      H(2)S exert cardioprotective effects in cultured cells, isolated hearts and
      various rodent and large animal models of regional or global myocardial ischemia
      and heart failure. In addition, the production of H(2)S plays a role in
      myocardial pre- and post-conditioning responses. The pathways implicated in the
      cardioprotective action of H(2)S are multiple and involve K(ATP) channels,
      regulation of mitochondrial respiration, and regulation of cytoprotective genes
      such as Nrf-2. In the experimental part of the current article, we demonstrate
      the cardioprotective effects of H(2)S in a canine model of cardiopulmonary bypass
      surgery. Anesthetized dogs were subjected hypothermic cardiopulmonary bypass with
      60 min of hypothermic cardiac arrest in the presence of either saline (control,
      n=8), or H(2)S infusion (1 mg/kg/h for 2 h). Left ventricular hemodynamic
      variables (via combined pressure-volume-conductance catheter) as well as coronary
      blood flow, endothelium-dependent vasodilatation to acetylcholine and endothelium
      independent vasodilatation to sodium nitroprusside were measured at baseline and
      after 60 min of reperfusion. Ex vivo vascular function and high-energy phosphate
      contents were also measured. H(2)S led to a significantly better recovery of
      preload recruitable stroke work (p<0.05) after 60 min of reperfusion. Coronary
      blood flow was also significantly higher in the H(2)S group (p<0.05). While the
      vasodilatory response to sodium nitroprusside was similar in both groups,
      acetylcholine resulted in a significantly higher increase in coronary blood flow
      in the H(2)S-treated group (p<0.05) both in vivo and ex vivo. Furthermore, high
      energy phosphate contents were better preserved in the H(2)S group. Additionally,
      the cytoprotective effects of H(2)S were confirmed also using in vitro cell
      culture experiments in H9c2 cardiac myocytes exposed to hypoxia and reoxygenation
      or to the cytotoxic oxidant hydrogen peroxide. Thus, therapeutic administration
      of H(2)S exerts cardioprotective effects in a variety of experimental models,
      including a significant improvement of the recovery of myocardial and endothelial
      function in a canine model of cardiopulmonary bypass with hypothermic cardiac
      arrest.

PMID- 21094269
TI  - PPS nanoparticles as versatile delivery system to induce systemic and broad
      mucosal immunity after intranasal administration.
AB  - Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide
      (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible
      disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a
      model antigen, and antigen-conjugated NPs were administered intranasally in the
      mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by
      antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin
      conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen
      tissues, as well as humoral response in mucosal airways. Co-conjugation of the
      TLR5 ligand flagellin further enhanced humoral responses in the airways as well
      as in the distant vaginal and rectal mucosal compartments and induced cellular
      immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP
      platform thus appears interesting as a platform for intranasally-administered
      mucosal vaccination for inducing broad mucosal immunity.

PMID- 21094270
TI  - Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic
      DNA vaccine for HIV-1, delivered by in vivo electroporation.
AB  - ADVAX is a DNA-based candidate HIV vaccine that was safe but weakly immunogenic
      when delivered intramuscularly (IM) in humans. Studies were performed in animal
      models to determine whether an alternative delivery method, in vivo
      electroporation (EP), could improve the immunogenicity of ADVAX while maintaining
      an acceptable safety profile. Immunization of mice with ADVAX with or without EP
      at weeks 0, 3, and 6, revealed significantly higher gamma interferon ELISpot
      responses to all antigens in the EP groups. Antigen-specific CD4+ and CD8+ T cell
      responses, as quantified by intracellular cytokine staining, both improved
      significantly with EP. Evaluation of repeat-dose toxicity of ADVAX-EP in rabbits
      did not reveal any safety concerns. Biodistribution studies of ADVAX delivered IM
      and with EP in rats indicated that the vaccine was localized predominantly to the
      administration site in both groups. PCR-based quantitation of residual plasmid at
      Day 60 indicated that the potential for integration events into the host genome
      was low for both IM and EP delivery. Taken together, these data supported the
      clinical development of ADVAX delivered with EP in human volunteers.

PMID- 21094271
TI  - Response to "Modeling the national pediatric vaccine stockpile: supply shortages,
      health impacts and cost consequences".

PMID- 21094272
TI  - Practical and theoretical characterization of Inga laurina Kunitz inhibitor on
      the control of Homalinotus coriaceus.
AB  - Digestive endoprotease activities of the coconut palm weevil, Homalinotus
      coriaceus (Coleoptera: Curculionidae), were characterized based on the ability of
      gut extracts to hydrolyze specific synthetic substrates, optimal pH, and
      hydrolysis sensitivity to protease inhibitors. Trypsin-like proteinases were
      major enzymes for H. coriaceus, with minor activity by chymotrypsin proteinases.
      More importantly, gut proteinases of H. coriaceus were inhibited by trypsin
      inhibitor from Inga laurina seeds. In addition, a serine proteinase inhibitor
      from I. laurina seeds demonstrated significant reduction of growth of H.
      coriaceus larvae after feeding on inhibitor incorporated artificial diets.
      Dietary utilization experiments show that 0.05% I. laurina trypsin inhibitor,
      incorporated into an artificial diet, decreases the consumption rate and fecal
      production of H. coriaceus larvae. Dietary utilization experiments show that
      0.05% I. laurina trypsin inhibitor, incorporated into an artificial diet,
      decreases the consumption rate and fecal production of H. coriaceus larvae. We
      have constructed a three-dimensional model of the trypsin inhibitor complexed
      with trypsin. The model was built based on its comparative homology with soybean
      trypsin inhibitor. Trypsin inhibitor of I. laurina shows structural features
      characteristic of the Kunitz type trypsin inhibitor. In summary, these findings
      contribute to the development of biotechnological tools such as transgenic plants
      with enhanced resistance to insect pests.

PMID- 21094273
TI  - High hydrophobic amino acid exposure is responsible of the neurotoxic effects
      induced by E200K or D202N disease-related mutations of the human prion protein.
AB  - Mutations in prion protein are thought to be causative of inherited prion
      diseases favoring the spontaneous conversion of the normal prion protein into the
      scrapie-like pathological prion protein. We previously reported that, by
      controlled thermal denaturation, human prion protein fragment 90-231 acquires
      neurotoxic properties when transformed in a beta-rich conformation, resembling
      the scrapie-like conformation. In this study we generated prion protein fragment
      90-231 bearing mutations identified in familial prion diseases (D202N and E200K),
      to analyze their role in the induction of a neurotoxic conformation. Prion
      protein fragment 90-231(wild type) and the D202N mutant were not toxic in native
      conformation but induced cell death only after thermal denaturation. Conversely,
      prion protein fragment 90-231(E200K) was highly toxic in its native structure,
      suggesting that E200K mutation per se favors the acquisition of a peptide
      neurotoxic conformation. To identify the structural determinants of prion protein
      fragment 90-231 toxicity, we show that while the wild type peptide is structured
      in alpha-helix, hPrP90-231 E200K is spontaneously refolded in a beta-structured
      conformer characterized by increased proteinase K resistance and propensity to
      generate fibrils. However, the most significant difference induced by E200K
      mutation in prion protein fragment 90-231 structure in native conformation we
      observed, was an increase in the exposure of hydrophobic amino-acids on protein
      surface that was detected in wild type and D202N proteins only after thermal
      denaturation. In conclusion, we propose that increased hydrophobicity is one of
      the main determinants of toxicity induced by different mutations in prion protein
      derived peptides.

PMID- 21094274
TI  - Genotoxicity assessment of an energetic propellant compound, 3-nitro-1,2,4
      triazol-5-one (NTO).
AB  - 3-Nitro-1,2,4-triazol-5-one (NTO) is an energetic explosive proposed for use in
      weapon systems, to reduce the sensitivity of warheads. In order to develop
      toxicity data for safety assessment, we investigated the genotoxicity of NTO,
      using a battery of genotoxicity tests, which included the Ames test, Chinese
      Hamster Ovary (CHO) cell chromosome aberration test, L5178Y TK(+/-) mouse
      lymphoma mutagenesis test and rat micronucleus test. NTO was not mutagenic in the
      Ames test or in Escherichia coli (WP2uvrA). NTO did not induce chromosomal
      aberrations in CHO cells, with or without metabolic activation. In the L5178Y
      TK(+/-) mouse lymphoma mutagenesis test, all of the NTO-treated cultures had
      mutant frequencies that were similar to the average frequencies of solvent
      control-treated cultures, indicating a negative result. Confirmatory tests for
      the three in vitro tests also produced negative results. The potential in vivo
      clastogenicity and aneugenicity of NTO was evaluated using the rat peripheral
      blood micronucleus test. NTO was administered by oral gavage to male and female
      Sprague-Dawley rats for 14 days at doses up to 2g/kg/day. Flow cytometric
      analysis of peripheral blood demonstrated no significant induction of
      micronucleated reticulocytes relative to the vehicle control (PEG-200). These
      studies reveal that NTO was not genotoxic in either in vitro or in vivo tests and
      suggest a low risk of genetic hazards associated with exposure.

PMID- 21094275
TI  - Ag colloids and Ag clusters over EDAPTMS-coated silica nanoparticles: synthesis,
      characterization, and antibacterial activity against Escherichia coli.
AB  - To produce better antibacterial water-insoluble nanocomposites of silver (Ag),
      silver-silicon dioxide (Ag-SiO(2)) hybrid and silver colloid (Ag-c) nanoparticles
      (NPs) were studied. Ag-c NPs were synthesized using reduction of AgNO(3), and Ag
      SiO(2) composites were prepared on a core of silica NPs functionalized with
      ethylenediamino-propyltrimethoxysilane, where Ag clusters were fabricated on
      amino groups using seed-mediated growth and characterized by transmission
      electron microscopy and ultraviolet-visible absorption spectroscopy.
      Antibacterial effectiveness of the Ag-SiO(2) NPs was tested against general
      Escherichia coli (E. coli ATCC 25922) and E. coli O157:H7 by measuring the growth
      based on optical density and digital counting of live-dead cells using a
      fluorescent microscope, and a field emission scanning electron microscope.
      Minimum inhibitory concentration values were studied against four representative
      bacteria along with E. coli O157:H7. Results showed that Ag NPs of 6.6 +/- 4.5 nm
      were attached to the surface of SiO(2) NPs (74 +/- 13.5 nm), and the Ag-c NPs
      (3.5 +/- 2 nm) showed excellent antibacterial properties. FROM THE CLINICAL
      EDITOR: In this paper, the synthesis of Ag colloids and Ag clusters over EDAPTMS
      coated silica nanoparticles is reported. Both NPs were examined for antibacterial
      effectiveness against representative bacteria including E. coli O157:H7 and found
      to have excellent antibacterial properties.

PMID- 21094276
TI  - Production of magnetic multilamellar liposomes as highly T2-efficient MRI
      contrast agents.
AB  - Lipid-based multilamellar vesicles loaded with aminosilane-modified maghemite
      nanoparticles (a-MNPs), also called magnetonions (MO), were analyzed for their
      magnetic resonance imaging (MRI) contrast agent properties. They were shown to be
      better T(2)-MRI contrast agents than commercial contrast agents and other
      reported liposome-based contrast agents as shown by their higher value of
      relaxivity ratio (r(2)/r(1) = 17), although a lower magnetic field intensity was
      used (0.2 T). Their high efficiency was explained by the aggregation of a-MNPs in
      between multilamellar vesicles, bilayers induced by MO preparation, and evidenced
      by cryo-TEM imaging. Magnetonions are then a promising platform for diagnosis and
      therapy. FROM THE CLINICAL EDITOR: In this study, magnetonions (MO) are presented
      as a very potent T2 relaxation enhancing MRI contrast agents. Such agents may be
      used in cell labeling and molecular imaging applications.

PMID- 21094278
TI  - In vitro protein adsorption studies on nevirapine nanosuspensions for HIV/AIDS
      chemotherapy.
AB  - Nevirapine is a poorly water-soluble antiretroviral drug. Intravenous nevirapine
      nanosuspensions (NS) (457 +/- 10 nm) were prepared by high-pressure
      homogenization. NS were surface modified by stabilizer adsorption, e.g., serum
      albumin, polysaccharide and polyethylene glycol (PEG) 1000. The NS were
      characterized for mean particle size, particle size distribution and
      polydispersity index. The targeting potential of the nonmodified and three
      surface-modified NS to the mononuclear phagocytic system (MPS) cells that serve
      as potent viral reservoirs was assessed by in vitro protein adsorption studies
      using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The
      adsorption patterns were qualitatively identical, but showed quantitative
      differences. The relatively adsorbed high amounts of immunoglobulins indicate
      uptake by liver and spleen, observed quantitative differences (e.g., the amount
      of dysopsonin albumin and apolipoproteins) can modulate the organ distribution.
      Controlled in vitro optimization of the protein adsorption by surface
      modification of the nanocrystals can reduce the number of animals required for in
      vivo studies and accelerate development of targeted nanoparticles. FROM THE
      CLINICAL EDITOR: In this study, intravenous nevirapine (a poorly water-soluble
      antiretroviral drug) nanosuspensions were prepared by high-pressure
      homogenization and characterized.

PMID- 21094277
TI  - Comparing cellular uptake and cytotoxicity of targeted drug carriers in cancer
      cell lines with different drug resistance mechanisms.
AB  - The purpose of this study was to compare the cellular uptake and cytotoxicity of
      targeted and nontargeted doxorubicin (DOX)-loaded poly(d,l-lactide co-glycolide)
      (PLGA) nanoparticle (NP) drug delivery systems in drug-resistant ovarian (SKOV-3)
      and uterine (MES-SA/Dx5) cancer cell lines. The cellular uptakes of DOX from
      nonconjugated DOX-loaded NPs (DNPs) and from HER-2 antibody-conjugated DOX-loaded
      NPs (ADNPs) in MES-SA/Dx5 cancer cells were higher compared to free DOX. Results
      also showed higher uptake of DOX from ADNPs in SKOV-3 cells compared with both
      free DOX and DNPs treatment. Cytotoxicity results at 10 MUM extracellular DOX
      concentration were consistent with the cellular uptake results. Our study
      concludes that cellular uptake and cytotoxicity of DOX can be improved in MES
      SA/Dx5 cells by loading DOX into PLGA NPs. DNPs targeted to membrane receptors
      may enhance cellular uptake and cytotoxicity in SKOV-3 cells. FROM THE CLINICAL
      EDITOR: The authors of this study compare the cellular uptake and cytotoxicity of
      targeted and nontargeted doxorubicin loaded PLGA nanoparticle delivery systems in
      drug-resistant ovarian and uterine cancer cell lines, concluding that cellular
      uptake and cytotoxicity of doxorubicin can be improved by the proposed methods.

PMID- 21094279
TI  - Nanomedicine and personalized medicine toward the application of pharmacotyping
      in clinical practice to improve drug-delivery outcomes.
AB  - Recent technological advances in nanomedicine and nanotechnology in parallel with
      knowledge accumulated from the clinical translation of disease- and drug-related
      genomic data have created fertile ground for personalized medicine to emerge as
      the new direction in diagnosis and drug therapy. To this end, the development of
      sophisticated nano-based systems for targeted drug delivery, along with the
      advent of pharmacogenomics, moves the drug-prescription process toward
      pharmacotyping, e.g., the individualized adjustment of drug selection and dosage.
      However, the clinical validity and utility of pharmacogenomic testing must be
      demonstrated by cost-effectiveness analysis and establishment of clinical
      practice reimbursement codes. Within this framework, and to achieve major
      benefits for all patients worldwide, a multidisciplinary scientific and
      technological infrastructure has to be organized in the healthcare system to
      address better the issues affecting regulatory environment, clinical pharmacology
      guidelines, education, bioethics and genomics data dissemination. FROM THE
      CLINICAL EDITOR: Individualized pharmacotyping, patient and disease-specific
      delivery of drugs, combining nanotechnology and pharmagenomics-based approaches
      would result in much more specific and efficient treatment of a variety of
      illnesses. While this clearly is one of the main cornerstones of individualized
      medicine; the cost effective integration of this complex technology is far from
      trivial, as discussed in details in this opinion paper.

PMID- 21094280
TI  - Identification of immunogenic consensus T-cell epitopes in globally distributed
      influenza-A H1N1 neuraminidase.
AB  - Antigenic drift is the ability of the swine influenza virus to undergo continuous
      and progressive changes in response to the host immune system. These changes
      dictate influenza vaccine updates annually to ensure inclusion of antigens of the
      most current strains. The identification of those peptides that stimulate T-cell
      responses, termed T-cell epitopes, is essential for the development of successful
      vaccines. In this study, the highly conserved and specific epitopes from
      neuraminidase of globally distributed H1N1 strains were predicted so that these
      potential vaccine candidates may escape with antigenic drift. A total of nine
      novel CD8(+) T-cell epitopes for MHC class-I and eight novel CD4(+) T-cell
      epitopes for MHC class-II alleles were proposed as novel epitope based vaccine
      candidates. Additionally, the epitope FSYKYGNGV was identified as a highly
      conserved, immunogenic and potential vaccine candidate, capable for generating
      both CD8(+) and CD4(+) responses.

PMID- 21094281
TI  - Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive
      individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study.
AB  - The HIV integrase enzyme is essential for the HIV life cycle as it mediates
      integration of HIV-1 proviral DNA into the infected cell's genome. Recently, the
      development of drugs capable of inhibiting integrase has provided major new
      options for HIV-infected, treatment-experienced patients with multidrug resistant
      virus, as well treatment-naive patients. More than 40 amino acid substitutions
      within integrase have been described as associated mostly with resistance of HIV
      B-subtypes to currently available integrase inhibitors (INIs). We have analyzed
      the natural polymorphisms of the integrase coding region in 87 antiretroviral
      naive subjects (32 from Cambodia, 37 from Thailand and 18 from Vietnam) infected
      with CRF01_AE virus, the predominant HIV-1 strain circulating in Southeast Asia.
      The 864bp integrase coding region was sequenced using the ANRS consensus
      sequencing technique from plasma samples, and amino acid results were interpreted
      for drug resistance according to the ANRS (Updated July 2009, version 18) and
      Stanford algorithms (Version November 6, 2009). Alignment of the 87 amino acid
      sequences against the 2004 Los Alamos HIV-1 clade B consensus sequence showed
      that overall, 119 of 288 (41.3%) amino acid positions presented at least one
      polymorphism each. Substitutions found in >60% of study subjects occurred at:
      K14, A21, V31, S39, I72, T112, T124, T125, G134, I135, K136, D167, V201, L234 and
      S283. Also, new amino acid substitutions of as yet unknown significance were
      identified: E152K/H, S153F/L, N155I and E157G. None of the known integrase
      resistance mutations were observed, except E157Q found in one Cambodian subject
      (1.1%, CI 95% 0.02-6.3%). The clinical impact of this substitution on resistance
      of B and nonB-viruses to the licensed INI raltegravir is unclear. If this
      substitution is confirmed to compromise the virologic response to raltegravir,
      further studies will be needed to better assess the prevalence of this
      substitution among CRF01_AE virus.

PMID- 21094282
TI  - Chronic hyperoxia alters the expression of neurotrophic factors in the carotid
      body of neonatal rats.
AB  - Chronic exposure to hyperoxia alters the postnatal development and innervation of
      the rat carotid body. We hypothesized that this plasticity is related to changes
      in the expression of neurotrophic factors or related proteins. Rats were reared
      in 60% O(2) from 24 to 36h prior to birth until studied at 3d of age (P3).
      Protein levels for brain-derived neurotrophic factor (BDNF) were significantly
      reduced (-70%) in the P3 carotid body, while protein levels for its receptor,
      tyrosine kinase B, and for glial cell line-derived neurotrophic factor (GDNF)
      were unchanged. Transcript levels in the carotid body were downregulated for the
      GDNF receptor Ret (-34%) and the neuropeptide Vgf (-67%), upregulated for Cbln1
      (+205%), and unchanged for Fgf2; protein levels were not quantified for these
      genes. Immunohistochemical analysis revealed that Vgf and Cbln1 proteins are
      expressed within the carotid body glomus cells. These data suggest that BDNF, and
      perhaps other neurotrophic factors, contribute to abnormal carotid body function
      following perinatal hyperoxia.

PMID- 21094283
TI  - Protein stability, flexibility and function.
AB  - Proteins rely on flexibility to respond to environmental changes, ligand binding
      and chemical modifications. Potentially, a perturbation that changes the
      flexibility of a protein may interfere with its function. Millions of mutations
      have been performed on thousands of proteins in quests for a delineation of the
      molecular details of their function. Several of these mutations interfered with
      the binding of a specific ligand with a concomitant effect on the stability of
      the protein scaffold. It has been ambiguous and not straightforward to recognize
      if any relationships exist between the stability of a protein and the affinity
      for its ligand. In this review, we present examples of proteins where changes in
      stability results in changes in affinity and of proteins where stability and
      affinity are uncorrelated. We discuss the possibility for a relationship between
      stability and binding. From the data presented is it clear that there are
      specific sites (flexibility hotspots) in proteins that are important for both
      binding and stability. This article is part of a Special Issue entitled: Protein
      Dynamics: Experimental and Computational Approaches.

PMID- 21094284
TI  - Senescence in cells in aseptic loosening after total hip replacement.
AB  - Particle-induced osteolysis is a major cause of aseptic loosening after total
      joint replacement. The purpose of the current study was to evaluate cellular
      senescence of macrophages and giant cells in patients with aseptic hip loosening
      by determination of SA-beta-Gal (SA-beta-galactosidase), a reliable and
      frequently used indicator of cellular senescence. The level of senescence in
      capsule and interface membranes was significantly higher in patients with aseptic
      loosening in comparison to specimens from patients without aseptic loosening.
      Using Spearman's rank correlation, we found that the expression of SA-beta-Gal in
      giant cells (p=0.002) and macrophages (p=0.050) in the interface membranes
      correlates significantly with the degree of polyethylene debris. We speculate
      that the induction of DNA damage by wear particles is responsible for premature
      senescence. Consequently, we conclude that the form of senescence observed in
      this study is a "stress-induced senescence".

PMID- 21094285
TI  - Subchondral cysts create increased intra-osseous stress in early knee OA: A
      finite element analysis using simulated lesions.
AB  - AIM OF STUDY: To investigate the role of intra-osseous lesions in advancing the
      pathogenesis of Osteoarthritis (OA) of the knee, using Finite Element Modeling
      (FEM) in conjunction with high-resolution imaging techniques. METHODS: Twenty
      early stage OA patients (<= Grade 2 radiographic score) were scanned with a
      prototype, cone-beam CT system. Scans encompassed the mid-shaft of the femur to
      the diaphysis of the proximal tibia. Individual bones were segmented to create 3D
      geometric models that were transferred to FE software for loading experiments.
      Patient-specific, inhomogeneous material properties were derived from the CT
      images and mapped directly to the FE models. Duplicate models were also created,
      with a 3D sphere (range 3-12 mm) introduced into a weight-bearing region of the
      joint, mimicking the size, location, and composition of a subchondral bone cyst
      (SBC). A spherical shell extending 1mm radially around the SBC served as the
      sample volume for measurements of von Mises equivalent stress. Both models were
      vertically loaded with 750 N, or approximately 1 body weight during a single-leg
      stance. RESULTS: All FE models exhibited a physiologically realistic weight
      bearing distribution of stress, which initiated at the joint surface and extended
      to the cortical bone. Models that contained the SBC experienced a nearly two-fold
      increase in stress (0.934 +/- 0.073 and 1.69 +/- 0.159 MPa, for the non-SBC and
      SBC models, respectively) within the bone adjacent to the SBC. In addition, there
      was a positive correlation found between the diameter of the SBC and the
      resultant intra-osseous stress under load (p = 0.004). CONCLUSIONS: Our results
      provide insights into the mechanism by which SBC may accelerate OA, leading to
      greater pain and disability. Based on these findings, we feel that patient
      derived FE models of the OA knee - utilizing in vivo imaging data - present a
      tremendous potential for monitoring joint mechanics under physiological loads.

PMID- 21094287
TI  - Curcumin promotes degradation of inducible nitric oxide synthase and suppresses
      its enzyme activity in RAW 264.7 cells.
AB  - Curcumin, a natural polyphenolic compound, has been reported to possess anti
      inflammatory properties. Previous works showed that curcumin decreased
      lipopolysaccharide (LPS)-induced iNOS up-regulation at transcription level.
      However, whether curcumin could regulate iNOS at the post-translational level is
      still unclear. In the present study, we demonstrated that curcumin promoted the
      degradation of iNOS which is expressed under LPS stimulation in murine macrophage
      like RAW 264.7 cells. Mechanically, such degradation of iNOS protein is due to
      ubiquitination and proteasome-dependency since it was almost completely blocked
      by N-benzoyloxycarbonyl-Leu-Leu-leucinal (MG132), a specific inhibitor of
      proteasome. Furthermore, curcumin decreased iNOS tyrosine phosphorylation through
      inhibiting ERK 1/2 activation and subsequently suppressed iNOS enzyme activity.
      In conclusion, our research displays a new finding that curcumin can promote the
      ubiqitination and degradation of iNOS after LPS stimulation.

PMID- 21094288
TI  - Invariant NKT cell development and function in microRNA-223 knockout mice.
AB  - Invariant natural killer T (iNKT) cells, potent regulators of diverse immune
      responses, have been implicated in a number of diseases. The detailed mechanisms
      that drive iNKT cell development and maturation are still not completely
      understood. MicroRNAs (miRNAs) are small noncoding RNAs that regulate vast
      networks of genes that share miRNA target sequences. Our previous studies
      indicate that Dicer-dependent miRNAs play important roles in iNKT cell
      development, maturation, and function, but the roles of specific single miRNAs in
      this context are still lacking. Accumulated studies indicated that the miRNA miR
      223 is a myeloid-specific miRNA. Here we report that miR-223 is highly expressed
      in thymic immature and activated splenic iNKT cells. To identify the role of miR
      223 in iNKT cell development and function, miRNA-223-deficient mice were used. We
      have found that miR-223 deletion does not significantly interrupt iNKT cell
      development in the thymus, and miR-223-deficient mice have a normal frequency and
      number of iNKT cells in the thymus and peripheral immune organs. Furthermore,
      cytokine production of iNKT cells activated in vivo and in vitro shows no
      significant differences between miR-223 deficient mice and wild-type control.
      Thus, our data suggest that miR-223 may not be required for iNKT cell development
      and function.

PMID- 21094289
TI  - Novel immunomodulatory effects of adiponectin on dendritic cell functions.
AB  - Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although
      it has been reported that ADN can inhibit the immunostimulatory function of
      monocytes and macrophages, little is known of its effect on dendritic cells (DC).
      Recent data suggest that ADN can regulate immune responses. DCs are uniquely
      specialised antigen presenting cells that play a central role in the initiation
      of immunity and tolerance. In this study, we have investigated the immuno-
      modulatory effects of ADN on DC functions. We found that ADN has only moderate
      effect on the differentiation of murine bone marrow (BM) derived DCs but altered
      the phenotype of DCs. The expression of major histocompatibilty complex class II
      (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on
      untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs.
      Interestingly, ADN treated DCs showed an increase in the expression of the
      inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated
      cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease
      in T cell proliferation and reduction of IL-2 production. Concomitant with that,
      a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was
      detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could
      partially restore T cell function. These findings suggest that the
      immunomodulatory effect of ADN on immune responses could be at least partially be
      mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the
      enhancement of Treg expansion are implicated in the immunomodulatory mechanisms.

PMID- 21094290
TI  - Paeoniflorin improves survival in LPS-challenged mice through the suppression of
      TNF-alpha and IL-1beta release and augmentation of IL-10 production.
AB  - Lipopolysaccharide (LPS) plays an important role in Gram-negative bacteria
      induced sepsis and multiple organ dysfunction syndrome, which are still the
      leading cause of high mortality in intensive care units. Although paeoniflorin
      (Pae) has reportedly exhibited anti-inflammatory effect and protection against
      immunological liver injury in mice, it is not known whether Pae improve survival
      in endotoxemic mice. The purpose of this study was to determine the effect of Pae
      on the mortality, multiple organ dysfunction and cytokine production in
      lipopolysaccharide (LPS)-treated mice. We found that pretreatment with Pae
      decreased mortality, reduced lung and kidney injury, decreased serum creatinine
      level and improve systolic function of heart in mice challenged with LPS. Further
      experiments showed that Pae inhibited LPS-stimulated tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1beta (IL-1beta) release and promoted LPS-induced
      interleukin-10 (IL-10) production. Our results indicate that Pae protects mice
      against lethal LPS challenge, at least in part, through inhibiting TNF-alpha and
      IL-1beta production and accelerating IL-10 expression.

PMID- 21094291
TI  - A comparison of workplace safety perceptions among financial decision-makers of
      medium- vs. large-size companies.
AB  - This study, through a random national survey in the U.S., explored how corporate
      financial decision-makers perceive important workplace safety issues as a
      function of the size of the company for which they worked (medium- vs. large-size
      companies). Telephone surveys were conducted with 404 U.S. corporate financial
      decision-makers: 203 from medium-size companies and 201 from large companies.
      Results showed that the patterns of responding for participants from medium- and
      large-size companies were somewhat similar. The top-rated safety priorities in
      resource allocation reported by participants from both groups were overexertion,
      repetitive motion, and bodily reaction. They believed that there were direct and
      indirect costs associated with workplace injuries and for every dollar spent
      improving workplace safety, more than four dollars would be returned. They
      perceived the top benefits of an effective safety program to be predominately
      financial in nature - increased productivity and reduced costs - and the safety
      modification participants mentioned most often was to have more/better safety
      focused training. However, more participants from large- than medium-size
      companies reported that "falling on the same level" was the major cause of
      workers' compensation loss, which is in line with industry loss data.
      Participants from large companies were more likely to see their safety programs
      as better than those of other companies in their industries, and those of medium
      size companies were more likely to mention that there were no improvements needed
      for their companies.

PMID- 21094292
TI  - The risk of pedestrian injury and fatality in collisions with motor vehicles, a
      social ecological study of state routes and city streets in King County,
      Washington.
AB  - This study examined the correlates of injury severity using police records of
      pedestrian-motor-vehicle collisions on state routes and city streets in King
      County, Washington. Levels of influence on collision outcome considered (1) the
      characteristics of individual pedestrians and drivers and their actions; (2) the
      road environment; and (3) the neighborhood environment. Binary logistic
      regressions served to estimate the risk of a pedestrian being severely injured or
      dying versus suffering minor or no injury. Significant individual-level
      influences on injury severity were confirmed for both types of roads: pedestrians
      being older or younger; the vehicle moving straight on the roadway. New variables
      associated with increased risk of severe injury or death included: having more
      than two pedestrians involved in a collision; and on city streets, the driver
      being inebriated. Road intersection design was significant only in the state
      route models, with pedestrians crossing at intersections without signals
      increasing the risk of being injured or dying. Adjusting for pedestrians' and
      drivers' characteristics and actions, neighborhood medium home values and higher
      residential densities increased the risk of injury or death. No other road or
      neighborhood environment variable remained significant, suggesting that
      pedestrians were not safer in areas with high pedestrian activity.

PMID- 21094293
TI  - Literature review of pedestrian fatality risk as a function of car impact speed.
AB  - The aim of this review was to evaluate all studies of pedestrian fatality risk as
      a function of car impact speed. Relevant papers were primarily investigated with
      respect to data sampling procedures and methods for statistical analysis. It was
      uniformly reported that fatality risk increased monotonically with car impact
      speed. However, the absolute risk estimates varied considerably. Without
      exceptions, papers written before 2000 were based on direct analyses of data that
      had a large bias towards severe and fatal injuries. The consequence was to
      overestimate the fatality risks. We also found more recent research based on less
      biased data or adjusted for bias. While still showing a steep increase of risk
      with impact speed, these later papers provided substantially lower risk estimates
      than had been previously reported.

PMID- 21094294
TI  - Unraveling the complexity of driving while intoxicated: a study into the
      prevalence of psychiatric and substance abuse comorbidity.
AB  - OBJECTIVE: Research is beginning to provide an indication of the co-occurring
      substance abuse and mental health needs for the driving under the influence (DUI)
      population. This study aimed to examine the extent of such psychiatric problems
      among a large sample size of DUI offenders entering treatment in Texas. METHODS:
      This is a study of 36,373 past year DUI clients and 308,714 non-past year DUI
      clients admitted to Texas treatment programs between 2005 and 2008. Data were
      obtained from the State's administrative dataset. RESULTS: Analysis indicated
      that non-past year DUI clients were more likely to present with more severe
      illicit substance use problems, while past year DUI clients were more likely to
      have a primary problem with alcohol. Nevertheless, a cannabis use problem was
      also found to be significantly associated with DUI recidivism in the last year.
      In regards to mental health status, a major finding was that depression was the
      most common psychiatric condition reported by DUI clients, including those with
      more than one DUI offence in the past year. This cohort also reported elevated
      levels of Bipolar Disorder compared to the general population, and such a
      diagnosis was also associated with an increased likelihood of not completing
      treatment. Additionally, female clients were more likely to be diagnosed with
      mental health problems than males, as well as more likely to be placed on
      medications at admission and more likely to have problems with methamphetamine,
      cocaine, and opiates. CONCLUSIONS: DUI offenders are at an increased risk of
      experiencing comorbid psychiatric disorders, and thus, corresponding treatment
      programs need to cater for a range of mental health concerns that are likely to
      affect recidivism rates.

PMID- 21094295
TI  - Mortality from road traffic accidents in Switzerland: longitudinal and spatial
      analyses.
AB  - Road traffic accidents (RTA) are an important cause of premature death. We
      examined socio-demographic and geographical determinants of RTA mortality in
      Switzerland by linking 2000 census data to RTA mortality records 2000-2005 (ICD
      10 codes V00-V99). Data from 5.5 million residents aged 18-94 years, 1744 study
      areas, and 1620 RTA deaths were analyzed, including 978 deaths (60.4%) in motor
      vehicle occupants, 254 (15.7%) in motorcyclists, 107 (6.6%) in cyclists, and 259
      (16.0%) in pedestrians. Weibull survival models and Bayesian methods were used to
      calculate hazard ratios (HR), and standardized mortality ratios (SMR) across
      study areas. Adjusted HR comparing women with men ranged from 0.04 (95% CI 0.02
      0.07) in motorcyclists to 0.43 (95% CI 0.32-0.56) in pedestrians. There was a u
      shaped relationship with age in motor vehicle occupants and motorcyclists. In
      cyclists and pedestrians, mortality increased after age 55 years. Mortality was
      higher in individuals with primary education (HR 1.53; 95% CI 1.29-1.81), and
      higher in single (HR 1.24; 95% CI 1.05-1.46), widowed (HR 1.31; 95% CI 1.05-1.65)
      and divorced individuals (HR 1.62; 95% CI 1.33-1.97), compared to persons with
      tertiary education or married persons. The association with education was
      particularly strong for pedestrians (HR 1.87; 95% CI 1.20-2.91). RTA mortality
      increased with decreasing population density of study areas for motor vehicle
      occupants (test for trend p<0.0001) and motorcyclists (p=0.0021) but not for
      cyclists (p=0.39) or pedestrians (p=0.29). SMR standardized for socio-demographic
      and geographical variables ranged from 82 to 190. Prevention efforts should aim
      to reduce inequities across socio-demographic and educational groups, and across
      geographical areas, with interventions targeted at high-risk groups and areas,
      and different traffic users, including pedestrians.

PMID- 21094296
TI  - A comprehensive analysis of factors influencing the injury severity of large
      truck crashes.
AB  - Given the importance of trucking to the economic well being of a country and the
      safety concerns posed by the trucks, a study of large-truck crashes is critical.
      This paper contributes by undertaking an extensive analysis of the empirical
      factors affecting injury severity of large-truck crashes. Data from a recent,
      nationally representative sample of large-truck crashes are examined to determine
      the factors affecting the overall injury severity of these crashes. The
      explanatory factors include the characteristics of the crash, vehicle(s), and the
      driver(s). The injury severity was modeled using two measures. Several
      similarities and some differences were observed across the two models which
      underscore the need for improved accuracy in the assessment of injury severity of
      crashes. The estimated models capture the marginal effects of a variety of
      explanatory factors simultaneously. In particular, the models indicate the
      impacts of several driver behavior variables on the severity of the crashes,
      after controlling for a variety of other factors. For example, driver distraction
      (truck drivers), alcohol use (car drivers), and emotional factors (car drivers)
      are found to be associated with higher severity crashes. A further interesting
      finding is the strong statistical significance of several dummy variables that
      indicate missing data - these reflect how the nature of the crash itself could
      affect the completeness of the data. Future efforts should seek to collect such
      data more comprehensively so that the true effects of these aspects on the crash
      severity can be determined.

PMID- 21094297
TI  - Excellent gamer, excellent driver? The impact of adolescents' video game playing
      on driving behavior: a two-wave panel study.
AB  - This study explored the impact of adolescents' playing of racing and drive'em up
      games on their risky driving behavior. Participants were 354 adolescent boys and
      girls who took part in a longitudinal panel survey on video game playing and risk
      taking attitudes, intentions and behaviors. In line with cultivation theory and
      theory of planned behavior the results showed that (even after controlling for
      aggression and sensation seeking) video game playing during adolescence succeeded
      in predicting later risky driving behavior through adolescents' attitudes and
      intentions to exhibit this behavior in the future. The results suggest that this
      relationship may in part be explained by the game content.

PMID- 21094298
TI  - Determination of pre-impact occupant postures and analysis of consequences on
      injury outcome. Part I: a driving simulator study.
AB  - This paper considers pre-impact vehicle maneuvers and analyzes the resulting
      driver motion from their comfort seating position. Part I of this work consists
      of analyzing the driver behavior during a crash. The study is conducted using the
      LAMIH driving simulator and involves 76 participants. The emergency situation is
      created by a truck emerging from behind a tractor on the opposite side of the
      road and tearing along the participant. The driver positioning throughout the
      simulation is recorded via five video cameras allowing view of the front scene,
      the driver face, feet and pedals, hands on the steering wheel and global lateral
      view. Data related to braking force, seat pressure, muscular activity for major
      groups of muscles and actions on the steering wheel are also collected. The
      typical response to this type of emergency event is to brace rearward into the
      seat and to straighten the arms against the steering wheel, or, to swerve to
      attempt to avoid the impacting vehicle. While turning the steering wheel, the
      forearm can be directly positioned on the airbag module at time of crash which
      represents a potential injurious situation. These positions are used in Part II
      to determine scenario of positions for numerical simulation of a frontal
      collision.

PMID- 21094299
TI  - Determination of pre-impact occupant postures and analysis of consequences on
      injury outcome--part II: biomechanical study.
AB  - This paper considers pre-impact vehicle maneuvers and analyzes the resulting
      driver motion from their comfort seating position. Part I of this work consisted
      of analyzing the driver behavior during a simulated crash in a car driving
      simulator. The configuration of the virtual accident led to an unavoidable
      frontal crash with a truck. The typical response to this type of emergency event
      was to brace rearward into the seat and to straighten the arms against the
      steering wheel, or, to swerve to attempt to avoid the impacting vehicle. In a
      turn crossover maneuvers, the forearm is directly positioned on the airbag module
      at time of crash. This position represents a potential injurious situation and is
      investigated in this Part II. Static airbag-deployment tests were realized in
      collaboration with Zodiac using conventional airbag (sewn cushion, pyrotechnical
      system and open event) and a Hybrid III 50th Male Dummy seated with the left arm
      positioned in the path of the deploying airbag. These experiments were
      numerically reproduced with Madymo and the ellipsoid Hybrid III dummy model. The
      dummy arm interaction with airbag was correlated with experiments. Then, a
      numerical simulation of a frontal collision at 56 km/h was realized. The results
      of the computational runs put forward injurious situations when the driver's arm
      was in front of the steering wheel. Indeed, in this case, the arm could hit the
      head under airbag deployment and induced serious neck bending and violent head
      launching. To mitigate head and neck trauma in this out-of-position situation, an
      airbag prototype (bonded cushion, two pure helium cold gas generators allowing
      mono- or multi-stage inflating, patented silicone membrane) was proposed by
      Zodiac. The results of static airbag-deployment tests with conventional and
      prototype airbags showed a significant reduction of the maximum linear head
      acceleration and neck bending with airbag prototype when a dual stage inflating
      was ignited, due to a reduced 'flinging' of the arm.

PMID- 21094300
TI  - Longitudinal relationship between economic development and occupational accidents
      in China.
AB  - The relativity between economic development and occupational accidents is a
      debated topic. Compared with the development courses of both economic development
      and occupational accidents in China during 1953-2008, this paper used statistic
      methods such as Granger causality test, cointegration test and impulse response
      function based on the vector autoregression model to investigate the relativity
      between economic development and occupational accidents in China from 1953 to
      2008. Owing to fluctuation and growth scale characteristics of economic
      development, two dimensions including economic cycle and economic scale were
      divided. Results showed that there was no relationship between occupational
      accidents and economic scale during 1953-1978. Fatality rate per 10(5) workers
      was a conductive variable to gross domestic product per capita during 1979-2008.
      And economic cycle was an indicator to occupational accidents during 1979-2008.
      Variation of economic speed had important influence on occupational accidents in
      short term. Thus it is necessary to adjust Chinese occupational safety policy
      according to tempo variation of economic growth.

PMID- 21094301
TI  - A full Bayes multivariate intervention model with random parameters among matched
      pairs for before-after safety evaluation.
AB  - The objective of this study is to evaluate the safety performance of a sample of
      intersections that have been improved with the implementation of certain safety
      countermeasures in the Greater Vancouver area. A full Bayes approach is utilized
      to determine the effectiveness of the improvements using a before-after design
      with matched (yoked) comparison groups. A multivariate Poisson-lognormal
      intervention model is used for the analysis of crash counts by severity levels.
      The model is extended to incorporate random parameters to account for the
      correlation between sites within comparison-treatment pairs. The full Bayes
      analysis revealed that incorporating such design features as matched comparison
      groups in the specification of safety performance functions can significantly
      improve the fit, while reducing the estimates of the extra-Poisson variation. As
      well, such extended models can be used to account for heterogeneity due to
      unobserved road geometrics, traffic characteristics, environmental factors and
      driver behavior. The results showed that the overall odds ratios for injuries and
      fatalities (I+F) and property damage only (PDO) imply significant reductions in
      predicted crash counts of 23% and 15%, respectively. The corresponding credible
      intervals were (12%, 33%) and (6%, 24%) at the 0.95 confidence level. The
      majority of the site-level odds ratio exhibited reductions in both I+F and PDO
      predicted crash counts. However, only some of these reductions were significant.
      As well, the effectiveness of the treatment seems to vary by severity level from
      one location to another. For I+F, the crash reduction factors were 29%, 15% and
      21% for improving signal visibility, left turn phase improvement and left turn
      lane installation, respectively. The corresponding crash reduction factors for
      PDO were 21%, 4% and 20%, respectively.

PMID- 21094302
TI  - The determinants of bicycle helmet use: evidence from Germany.
AB  - Previous research has shown that the risks of serious injury or death from
      bicycling can be mitigated by the decision to wear a helmet. Drawing on a
      nationwide household survey conducted in 2008 in Germany, this analysis
      investigates the determinants of voluntary helmet use through a combination of
      descriptive analyses and econometric methods, the latter relying on variants of
      the probit- and heteroskedastic probit model. Confirming results uncovered
      elsewhere in the literature, we find that household demographics, residential
      location, and riding patterns are significant correlates of helmet use.
      Contrasting with other studies, however, we also find that women are
      significantly less likely to use a helmet than men, a discrepancy that holds over
      most of the adult life-cycle. The paper concludes by highlighting the scope for
      designing strategic information campaigns to promote helmet use.

PMID- 21094303
TI  - Supporting drivers in forming correct expectations about transitions between
      rural road categories.
AB  - In order to support drivers in forming the right expectations on the road, road
      categories are being made recognisable and predictable in the Netherlands. The
      present study investigated which of the selected road layouts can make rural road
      categories most recognisable for road users, especially in transitions from one
      road category to another. A second objective was to study whether explicit
      information could contribute to a better recognisability of transitions. The
      experiment was performed with a series of photographs showing sections of two
      road categories with an intersection in between. The road layout of road
      categories varied in markings and separation of driving direction (within
      subjects factor). Informed and non-informed participants (between-subjects
      factor) had to indicate their expectations regarding speed limit and access
      restriction of each road section, before and after a transition. The results show
      that for transitions between distributor and through roads, the physicality of
      separation of driving direction is a better distinctive characteristic than the
      currently used edge marking. The green centre marking on through roads also
      enhances recognisability, but only with additional information. As far as
      transitions between distributor and access roads are concerned, the results
      demonstrate that this type of transitions is better recognised when no markings
      on access roads are present. Physical separation of driving directions on
      distributor roads also improves recognisability, although this layout is
      associated with higher speed limits. Providing explicit information has in
      general a positive effect on the reconisability of transitions. Implications are
      discussed in the light of potential safety effects.

PMID- 21094304
TI  - Identification and validation of a logistic regression model for predicting
      serious injuries associated with motor vehicle crashes.
AB  - A multivariate logistic regression model, based upon National Automotive Sampling
      System Crashworthiness Data System (NASS-CDS) data for calendar years 1999-2008,
      was developed to predict the probability that a crash-involved vehicle will
      contain one or more occupants with serious or incapacitating injuries. These
      vehicles were defined as containing at least one occupant coded with an Injury
      Severity Score (ISS) of greater than or equal to 15, in planar, non-rollover
      crash events involving Model Year 2000 and newer cars, light trucks, and vans.
      The target injury outcome measure was developed by the Centers for Disease
      Control and Prevention (CDC)-led National Expert Panel on Field Triage in their
      recent revision of the Field Triage Decision Scheme (American College of
      Surgeons, 2006). The parameters to be used for crash injury prediction were
      subsequently specified by the National Expert Panel. Model input parameters
      included: crash direction (front, left, right, and rear), change in velocity
      (delta-V), multiple vs. single impacts, belt use, presence of at least one older
      occupant (>= 55 years old), presence of at least one female in the vehicle, and
      vehicle type (car, pickup truck, van, and sport utility). The model was developed
      using predictor variables that may be readily available, post-crash, from OnStar
      like telematics systems. Model sensitivity and specificity were 40% and 98%,
      respectively, using a probability cutpoint of 0.20. The area under the receiver
      operator characteristic (ROC) curve for the final model was 0.84. Delta-V (mph),
      seat belt use and crash direction were the most important predictors of serious
      injury. Due to the complexity of factors associated with rollover-related
      injuries, a separate screening algorithm is needed to model injuries associated
      with this crash mode.

PMID- 21094305
TI  - Individual and occupational factors related to fatal occupational injuries: a
      case-control study.
AB  - This study has been designed in order to identify factors increasing the risk of
      a fatal outcome when occupational accidents occur. The aim is to provide further
      evidence for the design and implementation of preventive measures in occupational
      settings. The Spanish Ministry of Labour registry of occupational injuries
      causing absence from work includes information on individual and occupational
      characteristics of injured workers and events. Registered fatal occupational
      injuries in 2001 (n=539) were compared to a sample of non-fatal injuries in the
      same year (n=3493). Risks for a fatal result of occupational injuries, adjusted
      by individual and occupational factors significantly associated, were obtained
      through logistic regression models. Compared to non-fatal injuries, fatal
      occupational injuries were mostly produced by trapping or by natural causes,
      mostly related to elevation and transport devices and power generators, and
      injured parts of body more frequently affected were head, multiple parts or
      internal organs. Adjusted analyses showed increased risk of fatality after an
      occupational injury for males (adjusted odds ratio aOR=10.92; 95%CI 4.80-24.84)
      and temporary workers (aOR=5.18; 95%CI 2.63-10.18), and the risk increased with
      age and with advancing hour of the work shift (p for trends <0.01). Injuries
      taking place out of the usual occupational setting (aOR=2.85, 95%CI 2.27-3.59),
      or carrying out atypical tasks (aOR=2.08; 95%CI 1.27-3.39) showed increased risks
      of a fatal result too, as occupational accidents in agricultural or construction
      companies. These data can help to select and define priorities for programmes
      aimed to prevent fatal consequences of occupational injuries.

PMID- 21094306
TI  - Thirty-day self-reported risky driving behaviors of ADHD and non-ADHD drivers.
AB  - The present study aims to compare differences in reported risky driving behaviors
      of drivers - males and females - having and not having Attention Deficit
      Hyperactivity Disorder (ADHD), by using a checklist of driving behaviors based on
      the Driving Behavior Questionnaire (DBQ). Unlike the studies which employ the DBQ
      by asking the subjects to fill the questionnaire once, in this present study, the
      participants were asked to report their behaviors on a daily basis for 30
      consequent days. The checklist included two factors of risky driving behavior:
      Violation and Faults. Thirty-eight drivers - 10 males and 9 females with ADHD,
      and 9 males and 10 females without ADHD (N-ADHD) as control groups - participated
      in the study. The results showed that the mean of the unsafe behaviors of ADHD
      was higher, i.e., less safe driving, compared to that of N-ADHD. However, a
      statistically significant effect was found only between male ADHD and male N-ADHD
      for the Faults. In order to check the effect of the length of the study, the 30
      days duration of the research was divided into three consecutive periods. The
      reported driving habits of the female ADHD showed safer behaviors than those of
      the males. Unlike the findings of N-ADHD of both genders, which showed a tendency
      towards safer driving reports in the three periods, both genders of the ADHD
      showed higher rates of Faults, i.e., a decrease in safety driving reports, in the
      three periods. The findings suggest that ADHD drivers differ from the N-ADHD
      drivers in making driving mistakes, i.e., Faults, due to their lack of sustained
      attention, but not in making Violations. However, some of the results in the
      present study were not very strong. Possible explanations for this as well as
      methodological considerations are discussed, and further research is suggested.

PMID- 21094307
TI  - The choice to text and drive in younger drivers: behavior may shape attitude.
AB  - Following a previous study that reported a large number of young adult drivers
      text and drive, the current study investigated this behavior by looking at
      patterns of use and driver assessment of the risk of the behavior. The data from
      the current study converge with and extended the previous work showing 70% of the
      348 young adult drivers surveyed report initiating texts while driving while
      higher numbers reply to texts (81%) and read texts (92%) while driving.
      Additional drivers also report doing these behaviors, but only while stopped in
      traffic, showing only 2% never text and drive under any circumstances. The
      drivers indicated that they perceived these behaviors to be very risky and
      riskier than talking on a cell phone while driving, but perception of risk was a
      very weak predictor of behavior (for initiating texts) or had no effect on
      texting (for replying or reading texts while driving). In addition, a factor
      analysis of the perception of road conditions while texting revealed that making
      the choice to engage in texting (initiating) led drivers to perceive road
      conditions as being safer than if they replied to a text or read a text,
      suggesting that choosing to engage in the behavior itself changes attitudes
      toward risk.

PMID- 21094308
TI  - Pediatric short-distance household falls: biomechanics and associated injury
      severity.
AB  - OBJECTIVES: Short-distance household falls are a common occurrence in young
      children, but are also a common false history given by caretakers to conceal
      abusive trauma. The purpose of this study was to determine the severity of
      injuries that result from accidental short-distance household falls in children,
      and to investigate the association of fall environment and biomechanical measures
      with injury outcomes. METHODS: Children aged 0-4 years who presented to the
      Emergency Department with a history of a short furniture fall were included in
      the study. Detailed case-based biomechanical assessments were performed using
      data collected through medical records, interviews, and fall scene
      investigations. Injuries were rated using the Abbreviated Injury Scale (AIS).
      Each case was reviewed by a child abuse expert; cases with a vague or
      inconsistent history and cases being actively investigated for child abuse were
      excluded. RESULTS: 79 subjects were enrolled in the study; 15 had no injuries, 45
      had minor (AIS 1) injuries, 17 had moderate (AIS 2) injuries, and 2 had serious
      (AIS 3) injuries. No subjects had injuries classified as AIS 4 or higher, and
      there were no fatalities. Children with moderate or serious injuries resulting
      from a short-distance household fall tended to have fallen from greater heights,
      have greater impact velocities, and have a lower body mass index than those with
      minor or no injuries. CONCLUSION: Children aged 0-4 years involved in a short
      distance household fall did not sustain severe or life-threatening injuries, and
      no children in this study had moderate or serious injuries to multiple body
      regions. Biomechanical measures were found to be associated with injury severity
      outcomes in short-distance household falls. Knowledge of relationships between
      biomechanical measures and injury outcomes can aid clinicians when assessing
      whether a child's injuries were the result of a short-distance fall or some other
      cause.

PMID- 21094309
TI  - Computing what the public wants: some issues in road safety cost-benefit
      analysis.
AB  - In road safety, as in other fields, cost-benefit analysis (CBA) is used to
      justify the investment of public money and to establish priority between
      projects. It amounts to a computation by which 'few' - the CB analysts - aim to
      determine what the 'many' - those on behalf of which the choice is to be made -
      would choose. The question is whether there are grounds to believe that the tool
      fits the aim. I argue that the CBA tool is deficient. First, because estimates of
      the value of statistical life and injury on which the CBA computation rests are
      all over the place, inconsistent with the value of time estimates, and government
      guidance on the matter appears to be arbitrary. Second, because the premises of
      New Welfare Economics on which the CBA is founded apply only in circumstances
      which, in road safety, are rare. Third, because the CBA requires the computation
      of present values which must be questioned when the discounting is of future
      lives and of time. Because time savings are valued too highly when compared to
      life and because discounting tends to unjustifiably diminish the value of lives
      saved in the future, the CBA tends to bias decisions against investment in road
      safety.

PMID- 21094310
TI  - Young worker safety behaviors: development and validation of measures.
AB  - We conducted four studies to develop and validate measures of workplace safety
      related behaviors relevant to young workers. The conceptual basis for this set of
      measures is a range of behavioral responses to deteriorating conditions (e.g.,
      exit, voice, and loyalty, Hirschman, 1970; exit, voice, loyalty/patience, and
      neglect, Rusbult et al., 1982). In Study 1, items were generated by young workers
      (n=39) who participated in focus groups. The representativeness of these items
      was judged in Study 2 by a separate sample of young workers (n=79). In Study 3,
      we found support for five factors using exploratory factor analysis with a sample
      of young workers (n=266). Confirmatory factor analysis was conducted in Study 4
      using a separate sample (n=282) and this supported the five-factor model. Self
      report data on these participants and other-report (co-worker) data on a sub
      sample (n=26) of the same participants provided additional support for the
      validity of the scales. Overall, these studies support the validity and
      reliability of this set of safety-related behaviors: intentions to quit an unsafe
      job (exit), speaking out about safety concerns (voice), adapting to a dangerous
      job hoping that safety conditions improve (patience), deliberately letting safety
      conditions worsen (neglect), and following safety policies (compliance). This set
      is useful for evaluating safety interventions aimed at young workers and studying
      safety-related behavior in a vulnerable work population.

PMID- 21094311
TI  - Situational and personal characteristics associated with adverse weather
      encounters by pilots.
AB  - Weather conditions are significant hazards impacting the safe and efficient
      operation of aircraft. In this study, a large number of pilots were surveyed
      regarding weather events, and the circumstances associated with those events.
      Pilots completed a web-based questionnaire containing demographic questions, a
      risk perception scale, a hazardous events scale, and a pilot judgment scale. The
      pilots who reported a flight in which they penetrated weather without
      authorization or were concerned about the weather also completed 53 questions
      regarding their weather encounter. Usable data were obtained for 364
      participants: 144 who reported flying into weather, 114 who experienced a flight
      on which weather was a concern, and 106 who reported no flights on which weather
      was entered or was a major concern. Significant differences were evident between
      the three groups on the measures of pilot judgment, personal minimums, and
      hazardous events where pilots flying into weather recorded the poorest scores
      (least conservative minimums, most hazardous events, and poorest judgment).
      Significant differences were also noted between the two weather groups for a
      number of circumstances surrounding the events. Compared to the in-weather group,
      pilots in the near-weather group had acquired greater instrument hours, were
      older, and were more likely to have an instrument rating. Their aircraft were
      more likely to have an autopilot. More pilots in the in-weather group (28%)
      reported that they would be much more careful in the future regarding weather,
      compared to 17% of the near-weather group. The study provides data not previously
      obtained on both the situational and personal characteristics that are related to
      involvement in different degrees of weather-related encounters. These data should
      promote a better understanding of these individuals and the situations in which
      they are involved, and should inform future research and intervention efforts.

PMID- 21094312
TI  - Differing types of cellular phone conversations and dangerous driving.
AB  - This study sought to investigate the relationship between cell phone conversation
      type and dangerous driving behaviors. It was hypothesized that more emotional
      phone conversations engaged in while driving would produce greater frequencies of
      dangerous driving behaviors in a simulated environment than more mundane
      conversation or no phone conversation at all. Participants were semi-randomly
      assigned to one of three conditions: (1) no call, (2) mundane call, and, (3)
      emotional call. While driving in a simulated environment, participants in the
      experimental groups received a phone call from a research confederate who either
      engaged them in innocuous conversation (mundane call) or arguing the opposite
      position of a deeply held belief of the participant (emotional call).
      Participants in the no call and mundane call groups differed significantly only
      on percent time spent speeding and center line crossings, though the mundane call
      group consistently engaged in more of all dangerous driving behaviors than did
      the no call participants. Participants in the emotional call group engaged in
      significantly more dangerous driving behaviors than participants in both the no
      call and mundane call groups, with the exception of traffic light infractions,
      where there were no significant group differences. Though there is need for
      replication, the authors concluded that whereas talking on a cell phone while
      driving is risky to begin with, having emotionally intense conversations is
      considerably more dangerous.

PMID- 21094313
TI  - Gasoline prices and their relationship to drunk-driving crashes.
AB  - This study investigates the relationship between changing gasoline prices and
      drunk-driving crashes. Specifically, we examine the effects of gasoline prices on
      drunk-driving crashes in Mississippi by several crash types and demographic
      groups at the monthly level from 2004 to 2008, a period experiencing great
      fluctuation in gasoline prices. An exploratory visualization by graphs shows that
      higher gasoline prices are generally associated with fewer drunk-driving crashes.
      Higher gasoline prices depress drunk-driving crashes among young and adult
      drivers, among male and female drivers, and among white and black drivers.
      Results from negative binomial regression models show that when gas prices are
      higher, there are fewer drunk-driving crashes, particularly among property-damage
      only crashes. When alcohol consumption levels are higher, there are more drunk
      driving crashes, particularly fatal and injury crashes. The effects of gasoline
      prices and alcohol consumption are stronger on drunk-driving crashes than on all
      crashes. The findings do not vary much across different demographic groups.
      Overall, gasoline prices have greater effects on less severe crashes and alcohol
      consumption has greater effects on more severe crashes.

PMID- 21094314
TI  - A hazard perception test for novice drivers.
AB  - We developed a hazard perception test, modeled on that used currently in several
      Australian states, that presents short video scenes to observers and requires
      them to indicate the presence of a traffic conflict that would lead to a
      collision between the "camera" vehicle and another road user. After eliminating
      those scenes that were problematic (e.g., many observers did not recognize the
      hazard), we predicted driver group (novice vs. experienced drivers of similar
      age) on the basis of individual differences in reaction time, miss rate and false
      alarm rate. Novices were significantly slower in responding to hazards, even
      after controlling for age and simple reaction time. After selecting those scenes
      with the larger group differences, an 18-scene test that would be useful for mass
      testing exhibited even larger experience effects. There was good reliability in
      the resulting scale. Results suggest that this brief test of hazard perception
      can discriminate groups that differ in driving experience. Implications for
      driver licensing, evaluation and training are discussed.

PMID- 21094315
TI  - Comparison of factors influencing emergency department visits and hospitalization
      among drivers in work and nonwork-related motor vehicle crashes in Utah, 1999
      2005.
AB  - This study identified contributing factors in the occurrence of motor vehicle
      crashes (MVCs) and the severity of crashes according to work-related status in
      Utah. Analyses were based on probabilistically linked data involving police crash
      reports and hospital inpatient and emergency department (ED) records for the
      years 1999-2005. Of 643,647 drivers involved in crashes, 73,437 (11.4%) went to
      the emergency department (ED) and 4989 (0.8%) were hospitalized. Of the drivers
      in crashes visiting the ED, 2330 (3.2%) were working at the time of the crash and
      of drivers in crashes who were hospitalized, 235 (4.7%) were working at the time
      of the crash. There was no significant difference between those working versus
      not working at the time of the crash in safety belt use (82% [53,947/66,188] for
      ED cases and 60% [2,489/4,176] for hospitalized cases) or fatigue (4%
      [2,697/70,536] for ED cases and 9% [450/4,824] for hospitalized cases) among
      drivers in crashes, but there was a significant difference with respect to
      alcohol drinking between workers versus nonworkers (ED: 1% [31/2,237] vs. 5%
      [3,455/68,299], P<0.001; hospitalized: 3% [7/228] vs. 15% [673/4,596], P<0.001).
      Of those attending the ED because of a crash, workers were significantly more
      likely to have broken bones, bleeding wounds, or to die. Of those hospitalized
      because of a crash, workers were significantly less likely to have caused the
      crash (65% [145/223] vs. 73% [3,315/4,566], P<0.001). Yet although those drivers
      who were working at the time of the crash compared with those not working were
      less likely to have alcohol involved or to have caused the crash, there remains
      room for improvement among workers with respect to these factors, as well as
      safety belt use and fatigue.

PMID- 21094316
TI  - Prevalence rates of helmet use among motorcycle riders in a developed region in
      China.
AB  - This study aimed to determine the prevalence rates of helmet use, and of correct
      helmet use (chinstrap firmly fastened) among motorcycle riders and their
      passengers in Zhongshan, Guangdong Province, China. A cross-sectional survey
      involving direct observation of motorcycle riders was conducted at 20 randomly
      selected intersections. A total of 13,410 motorcycles were observed during a 10
      day period in February 2009. The overall prevalence of helmet use was 72.6% (95%
      CI: 71.8-73.3%) among drivers and 34.1% (95% CI: 32.7-35.5%) among pillion
      passengers. The prevalence of correct use was 43.2% (95% CI: 42.4-44.0%) and
      20.9% (95% CI: 19.8-22.1%) for drivers and passengers respectively. The helmet
      wearing rate on city streets was almost 95%, however city riders were more likely
      than rural riders to wear non-motorcycle helmets while riding. In multivariate
      analyses, factors associated with increased helmet use included riding on city
      streets, male gender, being a driver, carrying less passengers and riding a
      registered motorcycle. The results indicated enforcement and education activities
      need to be strengthened with respect to both helmet use and helmet quality,
      especially in rural areas, in order to improve wearing rates.

PMID- 21094317
TI  - Modeling animal-vehicle collisions using diagonal inflated bivariate Poisson
      regression.
AB  - Two types of animal-vehicle collision (AVC) data are commonly adopted for AVC
      related risk analysis research: reported AVC data and carcass removal data. One
      issue with these two data sets is that they were found to have significant
      discrepancies by previous studies. In order to model these two types of data
      together and provide a better understanding of highway AVCs, this study adopts a
      diagonal inflated bivariate Poisson regression method, an inflated version of
      bivariate Poisson regression model, to fit the reported AVC and carcass removal
      data sets collected in Washington State during 2002-2006. The diagonal inflated
      bivariate Poisson model not only can model paired data with correlation, but also
      handle under- or over-dispersed data sets as well. Compared with three other
      types of models, double Poisson, bivariate Poisson, and zero-inflated double
      Poisson, the diagonal inflated bivariate Poisson model demonstrates its
      capability of fitting two data sets with remarkable overlapping portions
      resulting from the same stochastic process. Therefore, the diagonal inflated
      bivariate Poisson model provides researchers a new approach to investigating AVCs
      from a different perspective involving the three distribution parameters
      (lambda(1), lambda(2) and lambda(3)). The modeling results show the impacts of
      traffic elements, geometric design and geographic characteristics on the
      occurrences of both reported AVC and carcass removal data. It is found that the
      increase of some associated factors, such as speed limit, annual average daily
      traffic, and shoulder width, will increase the numbers of reported AVCs and
      carcass removals. Conversely, the presence of some geometric factors, such as
      rolling and mountainous terrain, will decrease the number of reported AVCs.

PMID- 21094318
TI  - Early predictors of injury mortality among Swedish conscripts: a 35-year cohort
      study.
AB  - Injuries represent an important cause of mortality among young adults. We studied
      the associations between adolescents' family, psychological, behavioural and drug
      related risk factors in relation to unintentional injury death. A population
      based cohort of 49,411 Swedish conscripts aged 18-20 years was followed for 35
      years. The end-point of study was injury death up to 2004. The relationship
      between two family, four psychological and eight behavioural risk factors and
      injury death were analysed with Cox proportional hazards analyses and chi(2)
      tests. Among 485 unintentional injury deaths, 40% occurred in subjects aged 25
      years or under. The incidence per 1000 person years was 0.29 (95% CI, 0.26-0.31)
      and the mean age of death was 33 years. Problem drinking at both adolescent and
      adulthood was more strongly associated with injury death (HR=5.40) than illicit
      drug use (HR=2.70) even after adjusted for behavioural risk factors: (HR=3.43)
      and (HR=1.75), respectively. Adolescent risk factors such as contact with police
      and juvenile authorities, low emotional control, conduct problems at school and
      low social maturity were significant predictors of injury death in multivariate
      analyses. Young adults with social, behavioural and psychological problems and
      especially alcohol and drug use at both adolescent and adulthood have a high
      mortality rate due to road traffic injuries and all kind of injuries. Early
      identification of vulnerable groups of adolescents with psychological and
      behavioural problems including alcohol and drug use at local levels could make a
      difference.

PMID- 21094319
TI  - "Safety in Numbers" re-examined: can we make valid or practical inferences from
      available evidence?
AB  - "Safety in Numbers"(SIN), a recent concept in transportation research, policy and
      planning, has emerged as a causal inference from the non-linear statistical
      association between estimates of the numbers of walkers or bicyclists in an area
      and the rate or number of traffic collisions experienced by pedestrians or
      cyclists. Proponents of SIN argue that greater numbers of walkers or cyclists
      modify the hazardous behaviors of motor vehicle drivers thus creating safer
      conditions. This paper critically examines the research on the non-linear
      association as an adequate empirical basis for this causal interpretation. Given
      the paucity of evidence supporting a specific mechanism for the SIN effect,
      alternative plausible explanations of the non-linear association behind SIN, and
      a potential for unintended consequences from its policy application, the authors
      call for caution in the use of SIN in transportation policy and planning dialogue
      and decision-making.

PMID- 21094320
TI  - Time course of driving-skill self-assessments during French driver training.
AB  - Promoting self-assessment accuracy among student drivers could help improve the
      road safety for young novice drivers (Minimum Requirement for Driving Instructor
      Training, 2005). However, it is essential to first examine the time course of
      student drivers' assessments of their own driving skills. As a result, the
      present study examined the time course of student drivers' self-assessments in
      relation to their general driving abilities during the four steps of French
      driver training. We used Victoir et al.'s (2005) self-efficacy scale, which we
      translated into French. We set four goals for the present study: (1) to examine
      the psychometric qualities of this self-assessment scale, (2) to study the time
      courses of the students' self-assessments, (3) to investigate the relationship of
      these time courses to the number of driving hours that the students estimated
      that they needed to complete before taking the driving test, and (4) to compare
      the number of hours estimated by the students to the number of hours estimated by
      their driving instructors. In total, 150 students (58 men and 92 women) and 38
      instructors from 13 driving schools in Paris participated in the present study.
      The self-assessment scale was composed of 12 items that were rated on a 7-point
      Likert scale that ranged from 1 (certainly so) to 7 (certainly not). The internal
      consistency of the scale was satisfactory (alpha=.88). The self-assessments
      became increasingly positive as the training progressed (at the beginning of
      training, M=3.45 vs. at the completion of the training, M=4.8). Globally, the men
      assessed themselves more positively than the women. However, no significant
      gender difference was observed at each training step. The students' self-ratings
      were negatively correlated with the number of driving hours that they estimated
      they still needed before taking the driving test. This number did not differ
      significantly from the number of hours that was estimated by the instructors at
      each training step throughout the training. The results describing the time
      course of the student drivers' self-assessments during driver training and this
      time course's correlation with the estimated number of driving hours still needed
      to take the driver test were discussed.

PMID- 21094321
TI  - Enhancing hazard avoidance in teen-novice riders.
AB  - Research suggests that novice drivers' safety performance is inferior to that of
      experienced drivers in different ways. One of the most critical skills related to
      accident avoidance by a novice driver is the detection, recognition and reaction
      to traffic hazards; it is called hazard perception and is defined as the ability
      to identify potentially dangerous traffic situations. The focus of this research
      is to assess how far a motorcycle simulator could improve hazard avoidance skills
      in teenagers. Four hundred and ten participants (207 in the experimental group
      and 203 in the control group) took part in this research. Results demonstrated
      that the mean proportion of avoided hazards increases as a function of the number
      of tracks performed in the virtual training. Participants of the experimental
      group after the training had a better proportion of avoided hazards than
      participants of the control group with a passive training based on a road safety
      lesson. Results provide good evidence that training with the simulator increases
      the number of avoided accidents in the virtual environment. It would be
      reasonable to explain this improvement by a higher level of hazard perception
      skills.

PMID- 21094322
TI  - Assessing causality in multivariate accident models.
AB  - This paper discusses the application of operational criteria of causality to
      multivariate statistical models developed to identify sources of systematic
      variation in accident counts, in particular the effects of variables representing
      safety treatments. Nine criteria of causality serving as the basis for the
      discussion have been developed. The criteria resemble criteria that have been
      widely used in epidemiology. To assess whether the coefficients estimated in a
      multivariate accident prediction model represent causal relationships or are non
      causal statistical associations, all criteria of causality are relevant, but the
      most important criterion is how well a model controls for potentially confounding
      factors. Examples are given to show how the criteria of causality can be applied
      to multivariate accident prediction models in order to assess the relationships
      included in these models. It will often be the case that some of the
      relationships included in a model can reasonably be treated as causal, whereas
      for others such an interpretation is less supported. The criteria of causality
      are indicative only and cannot provide a basis for stringent logical proof of
      causality.

PMID- 21094323
TI  - Is a combined enforcement and penalty strategy effective in combating red light
      violations? An aggregate model of violation behavior in Hong Kong.
AB  - Red light violations are a major cause of traffic crashes at signalized
      intersections. In Hong Kong, prosecutions for red light violations have increased
      in the past decade. An automated enforcement camera system has been established
      to combat this prohibited driver behavior. In addition, both demerit points and
      financial penalties were revised upwards in 2006 to strengthen the deterrent
      effect of the system. An observational study of driver tendency to run a red
      light was conducted to evaluate the effectiveness of the combined penalty and
      camera strategy. Both the short- and long-term effects of the strategy on red
      light violations were estimated. The influences of factors including temporal
      variation, the presence of a red light camera, geometric design, and traffic
      control type were also determined with an aggregate count data model. The results
      show that the frequency of red light violations significantly decreased after the
      implementation of the new penalty system, and that the reduction remained
      significant one year after implementation. Interestingly, no evidence was found
      for an association between the frequency of red light violations and the presence
      of a red light camera.

PMID- 21094324
TI  - Evaluation of the Click It or Ticket intervention in Utah.
AB  - OBJECTIVE: To evaluate the Click It or Ticket (CIOT) intervention conducted in
      Utah by comparing changes in safety belt use using observational safety belt
      surveys pre- and post-intervention. METHODS: Observational surveys of safety belt
      use for drivers and front seat passengers (collectively referred to as front seat
      occupants) were conducted before and after the media and enforcement blitz of the
      CIOT intervention. Data were collected from 16 urban sites during the daytime and
      nighttime. Logistic regression and generalized estimating equations were used to
      compute odds ratios for safety belt use adjusted for front seat occupant
      characteristics. RESULTS: Overall safety belt use was observed at 76.5% pre
      intervention and 84.8% post-intervention, an improvement of 8.3% (95% confidence
      interval [CI]: 5.2%, 11.3%). Daytime and nighttime safety belt use improved by
      7.8% (95% CI: 3.5%, 12.1%) and 9.7% (95% CI: 6.4%, 13.0%), respectively. While
      males showed a greater improvement (9.9%) in safety belt use when compared to
      females (5.7%); males were still less likely to use safety belts than females.
      CONCLUSIONS: The CIOT intervention is associated with increased safety belt use
      at the sites observed in Utah, including among the two high risk groups targeted
      by the intervention: nighttime occupants and males.

PMID- 21094325
TI  - Effect of street pattern on the severity of crashes involving vulnerable road
      users.
AB  - Road crashes not only claim lives and inflict injuries but also create an
      economic burden to the society due to loss of productivity. Although numerous
      studies have been conducted to examine a multitude of factors contributing to the
      frequency and severity of crashes, very few studies have examined the influence
      of street pattern at a community level. This study examined the effect of
      different street patterns on crash severity using the City of Calgary as a case
      study. In this study, street pattern is classified into four categories: grid
      iron, warped parallel, loops and lollipops, and mixed patterns. Their effects on
      injury risk are examined together with other factors including road features,
      drivers' characteristics, crash characteristics, environmental conditions and
      vehicle attributes. Pedestrian and bicycle crash data for the years 2003-2005
      were utilized to develop a multinomial logit model of crash severity. Our results
      showed that compared to other street patterns, loops and lollipops design
      increases the probability of an injury but reduces the probability of fatality
      and property-damage-only in an event of a crash.

PMID- 21094326
TI  - The impact of climate change on winter road maintenance and traffic accidents in
      West Midlands, UK.
AB  - Winter weather can be a significant cause of road traffic accidents. This paper
      uses UKCIP climate change scenarios and a temporal analogue to investigate the
      relationship between temperature and severe road accidents in the West Midlands,
      UK. This approach also allows quantification of the changes in the severity of
      the winter season over the next century in the region. It is demonstrated that
      the predicted reduction in the number of frost days should in turn reduce the
      number of road accidents caused due to slipperiness by approximately 50%.
      However, the paper concludes by warning against complacency in winter maintenance
      regimes. A warmer climate may result in budget cuts for highway maintenance which
      in turn may well reverse declining accident trends.

PMID- 21094327
TI  - Safety impact of Gateway Monuments.
AB  - Gateway Monuments are free standing roadside structures or signage that
      communicate the name of a city, country or township to motorists. The placement
      of such monuments within state-controlled right-of-way is a relatively recent
      occurrence in California. As a result, the California Department of
      Transportation (Caltrans) initiated research to quantify the impacts that this
      type of signage may or may not have on crashes in their vicinity. To date, no
      specific research has examined the impact such features have on crashes. To
      determine whether these features impacted safety, the before-after study method
      using the Empirical Bayes technique was used, with reference groups and Safety
      Performance Functions adapted from existing studies, eliminating the need to
      calibrate new models. Results indicated that, on an individual basis, no
      deterioration in safety was observed at any monument site. When all sites were
      examined collectively (using two different scenarios), the calculated index of
      effectiveness values were 0.978 and 0.680, respectively, corresponding to 2.2%
      and 32.0% reductions in crashes. In addition to the EB method, naive study
      methods (with and without AADT taken into account) were applied to the study
      data. Results (crash reductions) from these methods also showed that the presence
      of Gateway Monuments did not have negative impact on traffic safety. However, the
      use of EB technique should be very careful employed when adopting reference
      groups from different jurisdictions, as these may affect the validity of EB
      results. In light of these results, Caltrans may continue to participate in the
      Gateway Monument Program at its discretion with the knowledge that roadway safety
      is not impacted by monuments.

PMID- 21094328
TI  - Visual assessment of pedestrian crashes.
AB  - Of the numerous factors that play a role in fatal pedestrian collisions, the time
      of day, day of the week, and time of year can be significant determinants. More
      than 60% of all pedestrian collisions in 2007 occurred at night, despite the
      presumed decrease in both pedestrian and automobile exposure during the night.
      Although this trend is partially explained by factors such as fatigue and alcohol
      consumption, prior analysis of the Fatality Analysis Reporting System database
      suggests that pedestrian fatalities increase as light decreases after controlling
      for other factors. This study applies graphical cross-tabulation, a novel visual
      assessment approach, to explore the relationships among collision variables. The
      results reveal that twilight and the first hour of darkness typically observe the
      greatest frequency of pedestrian fatal collisions. These hours are not
      necessarily the most risky on a per mile travelled basis, however, because
      pedestrian volumes are often still high. Additional analysis is needed to
      quantify the extent to which pedestrian exposure (walking/crossing activity) in
      these time periods plays a role in pedestrian crash involvement. Weekly patterns
      of pedestrian fatal collisions vary by time of year due to the seasonal changes
      in sunset time. In December, collisions are concentrated around twilight and the
      first hour of darkness throughout the week while, in June, collisions are most
      heavily concentrated around twilight and the first hours of darkness on Friday
      and Saturday. Friday and Saturday nights in June may be the most dangerous times
      for pedestrians. Knowing when pedestrian risk is highest is critically important
      for formulating effective mitigation strategies and for efficiently investing
      safety funds. This applied visual approach is a helpful tool for researchers
      intending to communicate with policy-makers and to identify relationships that
      can then be tested with more sophisticated statistical tools.

PMID- 21094329
TI  - A residential location approach to traffic safety: two case studies from Germany.
AB  - This paper aims to spatially differentiate the road accident risk associated with
      living at a certain place of residence. Official accident data usually record the
      place the accident occurred, but not the casualties' places of residence. Among
      those involved in an accident at a certain place there may obviously be some non
      residents, such as in-commuters and transients. Hence spatial analysis based on
      place of accident may not be suitable for drawing conclusions about specific risk
      levels for people living in certain places. People's risk of encountering an
      accident in areas other than that where they live may vary with their mobility.
      We report on two case studies for the German states of North Rhine-Westphalia and
      Lower Saxony, which are based on casualties' places of residence. We draw on two
      data sets both of which have specific advantages and disadvantages. From the data
      we calculate population-based risk figures on the district level and, for Lower
      Saxony, on the municipality level. For North Rhine-Westphalia these are
      categorised by age group and transport mode. We also investigate to what extent
      accident related analyses can be used to estimate residential related risks. The
      results show that the risk of being killed or seriously injured in a road
      accident is considerably lower for the population of agglomeration cores than for
      the suburban and rural population. Macro-economically this means that suburban
      and rural areas have markedly higher accident costs than cities.

PMID- 21094330
TI  - Riding through red lights: the rate, characteristics and risk factors of non
      compliant urban commuter cyclists.
AB  - This study determined the rate and associated factors of red light infringement
      among urban commuter cyclists. A cross-sectional observational study was
      conducted using a covert video camera to record cyclists at 10 sites across
      metropolitan Melbourne, Australia from October 2008 to April 2009. In total, 4225
      cyclists faced a red light and 6.9% were non-compliant. The main predictive
      factor for infringement was direction of travel, cyclists turning left (traffic
      travels on the left-side in Australia) had 28.3 times the relative odds of
      infringement compared to cyclists who continued straight through the
      intersection. Presence of other road users had a deterrent effect with the odds
      of infringement lower when a vehicle travelling in the same direction was present
      (OR=0.39, 95% CI 0.28-0.53) or when other cyclists were present (OR=0.26, 95% CI
      0.19-0.36). Findings suggest that some cyclists do not perceive turning left
      against a red signal to be unsafe and the opportunity to ride through the red
      light during low cross traffic times influences the likelihood of infringement.

PMID- 21094331
TI  - Safety climate and safety behavior in the passenger ferry context.
AB  - This research empirically evaluates safety climate and safety behavior in the
      passenger ferry context. Using survey data collected from 155 respondents working
      for passenger ferry companies in Taiwan, hierarchical regression analysis was
      used to examine the effects of safety climate on self-reported safety behaviors.
      Confirmatory factor analysis identified five main dimensions of safety climate as
      measured on a passenger ferry safety climate scale: safety policy, safety
      motivation, emergency preparedness, safety training, and safety communication.
      Further, safety training and emergency preparedness were found to positively
      affect self-reported safety behaviors with respect to safety compliance and
      safety participation. The study also revealed positive associations among
      respondents' age, ferry capacity, and safety compliance. Implications of the
      study findings for increasing safety in ferry operations and their contribution
      to the development of safety management are discussed.

PMID- 21094332
TI  - Quantification method analysis of the relationship between occupant injury and
      environmental factors in traffic accidents.
AB  - Injury analysis following a vehicle crash is one of the most important research
      areas. However, most injury analyses have focused on one-dimensional injury
      variables, such as the AIS (Abbreviated Injury Scale) or the IIS (Injury
      Impairment Scale), at a time in relation to various traffic accident factors.
      However, these studies cannot reflect the various injury phenomena that appear
      simultaneously. In this paper, we apply quantification method II to the NASS
      (National Automotive Sampling System) CDS (Crashworthiness Data System) to find
      the relationship between the categorical injury phenomena, such as the injury
      scale, injury position, and injury type, and the various traffic accident
      condition factors, such as speed, collision direction, vehicle type, and seat
      position. Our empirical analysis indicated the importance of safety devices, such
      as restraint equipment and airbags. In addition, we found that narrow impact,
      ejection, air bag deployment, and higher speed are associated with more severe
      than minor injury to the thigh, ankle, and leg in terms of dislocation, abrasion,
      or laceration.

PMID- 21094333
TI  - The contribution of a novel intervention to enhance safe driving among young
      drivers in Israel.
AB  - Young drivers in Israel, as in other parts of the world, are at an elevated risk
      of being involved in car crashes more than any other age group. A Graduated
      Driver Licensing System (GDL) has been introduced in Israel, requiring new
      drivers to be accompanied by an experienced driver during the first 3 months
      after obtaining a driving license. In an effort to ensure the effectiveness of
      the accompanied driving phase, a novel program which targets both young drivers
      and their parents, called green light for life (GLL), was initiated. This study
      aims to determine the effectiveness of GLL by comparing between young drivers who
      participated in the program and those who did not. Additionally, this study
      examined a structural equation model to predict young drivers' involvement in car
      crashes and additional risk measures. The study utilized quantitative measures
      through a questionnaire completed by 738 young drivers (437 men, 301 women; 362
      of whom participated in the program, 376 who did not). The results obtained
      indicate that GLL participants showed more positive views regarding the
      accompanied driving phase and were less involved in car crashes. They draw a
      comprehensive model of associations between various aspects of accompanied
      driving and risky driving measures.

PMID- 21094334
TI  - Participatory ergonomics: development of an employee assessment questionnaire.
AB  - Despite being essential to the success of participatory ergonomics (PEs)
      programs, there are currently no known quantitative measures that capture the
      employees' perspective of PE program effectiveness. The present study addresses
      this need through the development of the Employee Perceptions of Participatory
      Ergonomics Questionnaire (EPPEQ). The questionnaire is designed to assess five
      key components that are based on a review of the available literature: Employee
      Involvement, Knowledge Base, Managerial Support, Employee Support, and Strain
      related to ergonomic changes. In Phase 1, a sample of employees and ergonomists
      working at a manufacturing plant was used to develop and test an initial set of
      items. In Phase 2, data was collected from a nation-wide sample of employees
      representing a wide range of jobs and organizations to cross-validate the results
      from Phase 1. Phase 2 results indicate that the five EPPEQ subscales demonstrate
      sound convergent validity and are also correlated with traditional indicators of
      PE program success. Implications and uses of the EPPEQ are discussed.

PMID- 21094335
TI  - Analysis of large truck crash severity using heteroskedastic ordered probit
      models.
AB  - Long-combination vehicles (LCVs) have significant potential to increase economic
      productivity for shippers and carriers by decreasing the number of truck trips,
      thus reducing costs. However, size and weight regulations, triggered by safety
      concerns and, in some cases, infrastructure investment concerns, have prevented
      large-scale adoption of such vehicles. Information on actual crash performance is
      needed. To this end, this work uses standard and heteroskedastic ordered probit
      models, along with the United States' Large Truck Crash Causation Study, General
      Estimates System, and Vehicle Inventory and Use Survey data sets, to study the
      impact of vehicle, occupant, driver, and environmental characteristics on injury
      outcomes for those involved in crashes with heavy-duty trucks. Results suggest
      that the likelihood of fatalities and severe injury is estimated to rise with the
      number of trailers, but fall with the truck length and gross vehicle weight
      rating (GVWR). While findings suggest that fatality likelihood for two-trailer
      LCVs is higher than that of single-trailer non-LCVs and other trucks, controlling
      for exposure risk suggest that total crash costs of LCVs are lower (per vehicle
      mile traveled) than those of other trucks.

PMID- 21094337
TI  - Fatal train accidents on Europe's railways: 1980-2009.
AB  - This paper presents an analysis of fatal train accident rates and trends on
      Europe's main line railways from 1980 to 2009. The paper uses a new set of data
      for the European Union together with Norway and Switzerland, assembled partly
      under the auspices of the European Railway Agency and partly on the author's own
      account. The estimated overall trend in the number of fatal train collisions and
      derailments per train-kilometre is -6.3% per year from 1990 to 2009, with a 95%
      confidence interval of -8.7% to -3.9%. The estimated accident rate in 2009 is
      1.35 fatal collisions or derailments per billion train-kilometres, giving an
      estimated mean number of fatal accidents in 2009 of 6.0. The overall number of
      fatalities per fatal accident in 1990-2009 is 4.10, with no apparent long term
      change over time, giving an estimated mean of 24.6 fatalities per year in train
      collisions and derailments in 2009. There are statistically significant
      differences in the fatal train accident rates and trends between the different
      European countries, although the estimates of the rates and trends for many
      individual countries have wide confidence limits. The distribution of broad
      causes of accidents appears to have remained unchanged over the long term, so
      that safety improvements appear to have been across the board, and not focused on
      any specific cause. The most frequent cause of fatal train collisions and
      derailments is signals passed at danger. In contrast to fatal train collisions
      and derailments, the rate per train-kilometre of serious accidents at level
      crossings remained unchanged in 1990-2009. The immediate causes of most of the
      serious level crossing accidents are errors or violations by road users.

PMID- 21094336
TI  - Limits of spatial attention in three-dimensional space and dual-task driving
      performance.
AB  - The present study examined the limits of spatial attention while performing two
      driving relevant tasks that varied in depth. The first task was to maintain a
      fixed headway distance behind a lead vehicle that varied speed. The second task
      was to detect a light-change target in an array of lights located above the
      roadway. In Experiment 1 the light detection task required drivers to encode
      color and location. The results indicated that reaction time to detect a light
      change target increased and accuracy decreased as a function of the horizontal
      location of the light-change target and as a function of the distance from the
      driver. In a second experiment the light change task was changed to a singleton
      search (detect the onset of a yellow light) and the workload of the car following
      task was systematically varied. The results of Experiment 2 indicated that RT
      increased as a function of task workload, the 2D position of the light-change
      target and the distance of the light-change target. A multiple regression
      analysis indicated that the effect of distance on light detection performance was
      not due to changes in the projected size of the light target. In Experiment 3 we
      found that the distance effect in detecting a light change could not be explained
      by the location of eye fixations. The results demonstrate that when drivers
      attend to a roadway scene attention is limited in three-dimensional space. These
      results have important implications for developing tests for assessing crash risk
      among drivers as well as the design of in vehicle technologies such as head-up
      displays.

PMID- 21094338
TI  - Analysis of traffic accident injury severity on Spanish rural highways using
      Bayesian networks.
AB  - Several different factors contribute to injury severity in traffic accidents,
      such as driver characteristics, highway characteristics, vehicle characteristics,
      accidents characteristics, and atmospheric factors. This paper shows the
      possibility of using Bayesian Networks (BNs) to classify traffic accidents
      according to their injury severity. BNs are capable of making predictions without
      the need for pre assumptions and are used to make graphic representations of
      complex systems with interrelated components. This paper presents an analysis of
      1536 accidents on rural highways in Spain, where 18 variables representing the
      aforementioned contributing factors were used to build 3 different BNs that
      classified the severity of accidents into slightly injured and killed or severely
      injured. The variables that best identify the factors that are associated with a
      killed or seriously injured accident (accident type, driver age, lighting and
      number of injuries) were identified by inference.

PMID- 21094339
TI  - Spying or steering? Views of parents of young novice drivers on the use and
      ethics of driver-monitoring technologies.
AB  - In-vehicle technologies that document driving practices have the potential to
      enhance the driving safety of young drivers, but their installation depends
      largely on their parents' willingness and raises ethical dilemmas. This study
      investigated, using closed and open-ended questions, the views of 906 parents of
      young drivers in Israel regarding their willingness to install such a technology,
      and their conceptions of social norms and ethical issues associated with the
      technology and of factors that would encourage or discourage parents to adopt it.
      Most believed parents should feel morally obligated to install it. When cost was
      not a consideration, most said they would, and believed other parents would be
      willing to install the technology. Fewer (about half) expressed willingness to
      install it after being told about its estimated cost. Monetary cost was rated as
      a barrier to install it by about half. Environmental considerations were viewed
      as an incentive. Parents who supported the installation believed it would serve
      as a trigger for parent-young driver communication but those who did not thought
      it would erode trust in the parent-young driver relationship. Most said parents
      should have access to the monitoring data. Policy implications regarding issues
      of privacy and resources for parents are discussed.

PMID- 21094340
TI  - Temporal variations in road traffic fatalities in South Africa.
AB  - The annual road traffic fatality (RTF) burden of 43 deaths per 100000 inhabitants
      in South Africa (SA) is disproportionately high in comparison to the world
      average of 22 per 100000 population. Recent research revealed strong geographical
      variations across district councils in the country, as well as a substantial peak
      in mortality occurring during December. In this study, the factors that explain
      temporal variations in RTFs in SA are examined. Using weekly data from the period
      2002-2006 for the country's nine provinces, non-linear auto-regression exogenous
      (NARX) regression models were fitted to explain variations in RTFs and to assess
      the degree to which the variations between the provinces were associated with the
      temporal variations in risk factors. Results suggest that a proportion of the
      variations in weekly RTFs could be explained by factors other than the size of
      the province population, with both temporal and between-province residual
      variance remaining after accounting for the modelled risks. Policies directed at
      reducing the effects of the modifiable risks identified in our study will be
      important in reducing RTFs in SA.

PMID- 21094341
TI  - Multi-scale traffic safety and operational performance study of large trucks on
      mountainous interstate highway.
AB  - In addition to multi-vehicle accidents, large trucks are also prone to single
      vehicle accidents on the mountainous interstate highways due to the complex
      terrain and fast-changing weather. By integrating both historical data analysis
      and simulations, a multi-scale approach is developed to evaluate the traffic
      safety and operational performance of large trucks on mountainous interstate
      highways in both scales of individual vehicle as well as traffic on the whole
      highway. A typical mountainous highway in Colorado is studied for demonstration
      purposes. Firstly, the ten-year historical accident records are analyzed to
      identify the accident-vulnerable-locations (AVLs) and site-specific critical
      adverse driving conditions. Secondly, simulation-based single-vehicle assessment
      is performed for different driving conditions at those AVLs along the whole
      corridor. Finally, the cellular-automaton (CA)-based simulation is carried out to
      evaluate the multi-vehicle traffic safety as well as the operational performance
      of the traffic by considering the actual speed limits, including the differential
      speed limits (DSL) at some locations. It is found that the multi-scale approach
      can provide insightful and comprehensive observations of the highway performance,
      which is especially important for mountainous highways.

PMID- 21094342
TI  - Pedestrian crash estimation models for signalized intersections.
AB  - The focus of this paper is twofold: (1) to examine the non-linear relationship
      between pedestrian crashes and predictor variables such as demographic
      characteristics (population and household units), socio-economic characteristics
      (mean income and total employment), land use characteristics, road network
      characteristics (the number of lanes, speed limit, presence of median, and
      pedestrian and vehicular volume) and accessibility to public transit systems, and
      (2) to develop generalized linear pedestrian crash estimation models (based on
      negative binomial distribution to accommodate for over-dispersion of data) by the
      level of pedestrian activity and spatial proximity to extract site specific data
      at signalized intersections. Data for 176 randomly selected signalized
      intersections in the City of Charlotte, North Carolina were used to examine the
      non-linear relationships and develop pedestrian crash estimation models. The
      average number of pedestrian crashes per year within 200 feet of each
      intersection was considered as the dependent variable whereas the demographic
      characteristics, socio-economic characteristics, land use characteristics, road
      network characteristics and the number of transit stops were considered as the
      predictor variables. The Pearson correlation coefficient was used to eliminate
      predictor variables that were correlated to each other. Models were then
      developed separately for all signalized intersections, high pedestrian activity
      signalized intersections and low pedestrian activity signalized intersections.
      The use of 0.25mile, 0.5mile and 1mile buffer widths to extract data and develop
      models was also evaluated.

PMID- 21094343
TI  - Developing a tool to measure safe recreational boating practice.
AB  - To reduce the number of recreational boating injuries and incidents, appropriate
      educational measures are important to improve boat operator safety practice. A
      tool (the boating safety scale (BSS)) to measure safe practice was developed and
      tested among Western Australian recreational boaters. The BSS allowed the
      identification of factors influencing safety behaviour among recreational
      boaters. Using a database of registered recreational vessels, a telephone survey
      was conducted in 2008 among a sample of 1002 boat owners and a response fraction
      of 47.5% was achieved. The majority of boaters displayed a moderate level of safe
      boating behaviour based on BSS scores. Not being a member of a boating
      association and going boating less often in protected waters was associated with
      a higher level of boating safety behaviour. With further development, the BSS can
      provide information to assist is designing effective intervention strategies to
      reduce the number of boating-related fatalities, injuries and incidents.

PMID- 21094344
TI  - A study of the effectiveness of Electronic Stability Control in Canada.
AB  - Electronic Stability Control (ESC) is a crash avoidance system found on many
      vehicles. Unlike air bags, which only help during a collision, ESC helps to avoid
      a loss of control that could lead to a collision by preventing skidding. ESC is
      designed to help the driver stay in control of the vehicle during an emergency
      manoeuvre, such as when the driver needs to swerve to avoid an obstacle. Our
      study is an effectiveness evaluation of ESC using crash data. The purpose of a
      Canadian evaluation study is to examine whether there is an issue with multi
      vehicle crashes, and whether ESC is effective in Canadian weather conditions,
      i.e. on ice, snow and slush. Our results show that ESC is effective for all ESC
      sensitive crashes (41.1% effectiveness) and its effectiveness is higher for ESC
      sensitive injury crashes only (54.8% effectiveness). In particular, ESC is
      effective in the case of all multi-vehicle ESC-sensitive crashes (23.2%
      effectiveness) and of multi-vehicle ESC-sensitive injury crashes (28.4%
      effectiveness). ESC is also effective for single-vehicle ESC-sensitive crashes,
      both for all severities of crashes (18.6% effectiveness) and injury crashes only
      (49.3% effectiveness). The results of the study also show that ESC is effective
      in Canadian weather conditions (i.e. on ice, snow and slush). The effectiveness
      of ESC on roads covered with ice, snow and slush is 51.1% for ESC-sensitive
      crashes of all severities and 71.1% for ESC-sensitive injury crashes. ESC is also
      effective on dry roads (36.3% effectiveness for ESC-sensitive crashes of all
      severities and 46.6% effectiveness for ESC-sensitive injury crashes), wet roads
      (35.8% effectiveness for ESC-sensitive crashes of all severities and 49.5%
      effectiveness for ESC-sensitive injury crashes) and for both cars (28.5%
      effectiveness for ESC-sensitive crashes of all severities and 43.7% effectiveness
      for ESC-sensitive injury crashes) and LTVs (51.9% effectiveness for ESC-sensitive
      crashes of all severities and 69.6% effectiveness for ESC-sensitive injury
      crashes).

PMID- 21094345
TI  - Analyzing angle crashes at unsignalized intersections using machine learning
      techniques.
AB  - A recently developed machine learning technique, multivariate adaptive regression
      splines (MARS), is introduced in this study to predict vehicles' angle crashes.
      MARS has a promising prediction power, and does not suffer from interpretation
      complexity. Negative Binomial (NB) and MARS models were fitted and compared using
      extensive data collected on unsignalized intersections in Florida. Two models
      were estimated for angle crash frequency at 3- and 4-legged unsignalized
      intersections. Treating crash frequency as a continuous response variable for
      fitting a MARS model was also examined by considering the natural logarithm of
      the crash frequency. Finally, combining MARS with another machine learning
      technique (random forest) was explored and discussed. The fitted NB angle crash
      models showed several significant factors that contribute to angle crash
      occurrence at unsignalized intersections such as, traffic volume on the major
      road, the upstream distance to the nearest signalized intersection, the distance
      between successive unsignalized intersections, median type on the major approach,
      percentage of trucks on the major approach, size of the intersection and the
      geographic location within the state. Based on the mean square prediction error
      (MSPE) assessment criterion, MARS outperformed the corresponding NB models. Also,
      using MARS for predicting continuous response variables yielded more favorable
      results than predicting discrete response variables. The generated MARS models
      showed the most promising results after screening the covariates using random
      forest. Based on the results of this study, MARS is recommended as an efficient
      technique for predicting crashes at unsignalized intersections (angle crashes in
      this study).

PMID- 21094347
TI  - Effect of a road safety training program on drivers' comparative optimism.
AB  - Reducing comparative optimism regarding risk perceptions in traffic accidents has
      been proven to be particularly difficult (Delhomme, 2000). This is unfortunate
      because comparative optimism is assumed to impede preventive action. The present
      study tested whether a road safety training course could reduce drivers'
      comparative optimism in high control situations. Results show that the training
      course efficiently reduced comparative optimism in high control, but not in low
      control situations. Mechanisms underlying this finding and implications for the
      design of road safety training courses are discussed.

PMID- 21094346
TI  - Predictive factors of chronic post-traumatic stress disorder 6 months after a
      road traffic accident.
AB  - BACKGROUND: This study sets out to identify risk factors for post-traumatic
      stress disorder (PTSD) after a road traffic accident with a view to improving
      prevention. METHODS: The study used a prospective cohort of road traffic accident
      casualties. All subjects over 15 years of age were recruited in the course of an
      interview conducted while they were receiving care in a hospital of the Rhone
      area administrative departement. Six months after their accident, they answered a
      self-administered postal questionnaire that included the Post-traumatic Check
      List Scale (PCLS) in order to evaluate PTSD. Multivariate logistic regression
      analysis was conducted to compare those subjects with a PCLS score of 44 or over
      with those with a lower score, in order to identify factors that might be
      associated with PTSD. RESULTS: 592 subjects (out of 1168) returned the 6-month
      questionnaire and 541 completed the PCLS test. One hundred subjects had a PCLS
      score >= 44, suggesting PTSD, and 441 subjects did not. The factors associated
      with PTSD were initial injury severity, post-traumatic amnesia, the feeling of
      not being responsible for their accident and persistent pain 6 months after it. A
      lower odds-ratio was associated with users of two-wheel than four-wheel motor
      vehicles (OR=0.4; 0.2-0.9). CONCLUSION: Besides predictive factors for PTSD
      (injury severity, post-traumatic amnesia and the feeling of not being responsible
      for their accident), our study suggested a reduced risk of PTSD among two-wheel
      motor vehicle users.

PMID- 21094348
TI  - Effects of roadside memorials on traffic flow.
AB  - Despite their growing popularity in North America, little research has been
      conducted on understanding the effects of roadside memorials on drivers'
      behaviour. In this study, we examined the short-term effects of roadside
      memorials on traffic speed and headways on a high speed intercity freeway as well
      as its long-term effect on traffic speed on a high speed urban freeway. Our study
      found that the placement of roadside memorials did not have any significant
      effect on traffic speeds or headways, either in the short or long term.
      Therefore, concerns about the negative effects on driver behaviour were not
      supported by this research, at least with regards to speeding and following too
      closely. However, no positive effects on safety were found either.

PMID- 21094349
TI  - Licence restrictions as an under-used strategy in managing older driver safety.
AB  - While many older drivers remain unimpaired or otherwise effectively compensate
      for functional deficits, a minority are currently faced with two main options:
      either continue to drive with arguably an unacceptable crash risk; or cease
      driving, perhaps at the instigation of licensing authorities. Licence
      restrictions represent a possible third option for some older drivers, by better
      managing crash risk while still allowing acceptable levels of mobility. The
      present study has explored licence restrictions as applied to Victorian older
      drivers over a ten-year period. It has identified the types of restrictions and
      their extent of use in recent years, plus indications of potential safety
      benefits that may result from restricted licencing practices. Less than 10% of
      the older driver cohort had a licence restriction and in around 95% of instances,
      the restriction related to the need to wear corrective lenses; these numbers
      precluded a conclusive evaluation of safety benefits. However, two important
      findings emerged. First, the imposition of a licence restriction was usually
      associated with a reduction in absolute crash rates. Second, three restrictions
      were identified that most readily form the basis of a graduated driving reduction
      program.

PMID- 21094350
TI  - Predictors of reperfusion delay in patients with acute myocardial infarction
      undergoing primary percutaneous coronary intervention from the HORIZONS-AMI
      trial.
AB  - Primary percutaneous coronary intervention (PCI) is the optimal method of
      reperfusion when performed expeditiously. Factors contributing to delays in PCI
      for ST-segment elevation myocardial infarction (STEMI) have not been thoroughly
      characterized or quantified. We sought to identify the factors associated with
      the delays to reperfusion in patients with STEMI undergoing primary PCI. Primary
      PCI was performed in 3,340 patients with STEMI in the international, multicenter
      Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial
      Infarction trial. Multivariate analysis was used to identify independent
      predictors of delay in achieving reperfusion from 38 baseline and procedural
      variables. A total of 905 patients (27.1%) presented to non-PCI hospitals and
      were subsequently transferred; the remainder presented to PCI hospitals. The most
      powerful independent predictor of the interval from symptom onset to arrival at
      the PCI hospital and the first door-to-balloon time was an initial presentation
      at a non-PCI hospital (median incremental 58- and 54-minute delay, respectively,
      both p < 0.001). Other independent predictors of prolonged door-to-balloon times
      included presentation with respiratory failure (42-minute incremental delay, p =
      0.003), presentation during off-work hours (11-minute incremental delay, p <
      0.001), and co-morbid conditions such as diabetes and heart failure. In
      conclusion, among patients undergoing primary PCI, presentation to a non-PCI
      hospital was the variable associated with the greatest delay to reperfusion.
      Systems of care that encourage ambulance diagnosis and direct delivery of
      patients with STEMI to a PCI hospital might shorten the overall door-to-balloon
      times and improve the clinical outcomes.

PMID- 21094351
TI  - Usefulness of decrease in oxygen uptake efficiency slope to identify myocardial
      perfusion defects in men undergoing myocardial ischemic evaluation.
AB  - Cardiopulmonary exercise testing (CPX) might aid in the diagnosis of coronary
      artery disease. However, a heterogeneous clinical population without previous
      workup bias has not been studied nor has a more extensive list of CPX variables.
      A total of 303 subjects (age 49.9 +/- 11.6 years, 157 men) with symptoms
      suggestive of coronary artery disease underwent CPX and a single photon emission
      computed tomographic myocardial perfusion study (MPS). Ventilatory efficiency was
      calculated using the oxygen uptake efficiency slope (OUES). The change in the
      OUES was calculated by subtracting the OUES response during the first 50% of CPX
      from the OUES obtained during the last 25% of CPX. A negative change in the OUES
      (< 0) from the first 50% to the last 25% of CPX was predictive of positive MPS
      findings only in the male subjects. The diagnostic significance of the change in
      OUES in men was found for any level (including equivocal studies) of positive MPS
      findings (area under the curve 0.67, 95% confidence interval 0.59 to 0.76, p <
      0.0001) and was even stronger in those with a more definitive (excluding
      equivocal studies) perfusion defect (area under the curve 0.76, 95% confidence
      interval 0.67 to 0.85; relative risk 5.4, 95% confidence interval 2.1 to 13.8, p
      < 0.0001). In conclusion, this is the first time that a change in ventilatory
      efficiency, assessed using the OUES, has been shown to be predictive of positive
      MPS findings However, the OUES change only provided diagnostic information for
      men, a finding that warrants additional analysis.

PMID- 21094352
TI  - Usefulness of intraplatelet melatonin levels to predict angiographic no-reflow
      after primary percutaneous coronary intervention in patients with ST-segment
      elevation myocardial infarction.
AB  - Platelet aggregates appear to have a pathogenic role in the no-reflow phenomenon,
      which is associated with impaired clinical outcome in patients with ST-segment
      elevation myocardial infarction (STEMI). Melatonin, a hormone that plays a major
      role in biological circadian rhythms, is present in human platelets. Lowered
      circulating melatonin levels predict poor outcome in patients with STEMI
      undergoing primary percutaneous coronary intervention (PPCI). We investigated
      whether intraplatelet melatonin levels correlate with angiographic no-reflow
      after PPCI in patients with STEMI. We studied 180 consecutive patients with a
      first STEMI who underwent PPCI within 6 hours from onset of symptoms.
      Intraplatelet melatonin levels were measured in platelet-rich plasma using an
      enzymatic immunoassay method. After PPCI, angiographic no-reflow (defined as
      Thrombolysis In Myocardial Infarction grade < 2 flow) was observed in 63 patients
      (35%). Patients with angiographic no-reflow had lower intraplatelet melatonin
      levels compared to patients without no-reflow (12.32 +/- 3.64 vs 18.62 +/- 3.88
      ng/100,000 platelets, p < 0.0001). After adjusting by potential confounders,
      binary logistic regression analysis showed that intraplatelet melatonin levels
      were the only significant predictor of angiographic no-reflow (odds ratio 1.58,
      95% confidence interval 1.37 to 1.82, p < 0.0001). In conclusion, low
      intraplatelet melatonin concentration predicts angiographic no-reflow after PPCI
      in patients with STEMI.

PMID- 21094353
TI  - United States stock market performance and acute myocardial infarction rates in
      2008-2009 (from the Duke Databank for Cardiovascular Disease).
AB  - We sought to examine the relation between the United States economic decrease in
      2008 and cardiovascular events as measured by local acute myocardial infarction
      (AMI) rates. Mental stress and traumatic events have been shown to be associated
      with increased risk of MI in patients with ischemic heart disease. This was an
      observational study of data from the Duke Databank for Cardiovascular Disease and
      includes patients undergoing angiography for evaluation of ischemic heart disease
      from January 2006 to July 2009. Patients with AMI occurring within 3 days before
      catheterization were used to calculate AMI rates. Stock market values were
      examined to determine the period of severe economic decrease, and time trends in
      AMI rates were examined over the same period. Time series models were used to
      assess the relation between United States stock market National Association of
      Securities Dealers Automated Quotation (NASDAQ) and rates of AMI. Of 11,590
      patients included in the study cohort, 2,465 patients had an AMI during this
      period. Time series analysis showed a significant increase in AMI rates during a
      period of stock market decrease from October 2008 to April 2009 (p = 0.003),
      which remained statistically significant when adjusted for seasons (p = 0.02). In
      conclusion, unadjusted and adjusted analyses of patients in the Duke Databank for
      Cardiovascular Disease indicated a significant correlation between a period of
      stock market decrease and increased AMI rates in our local cohort.

PMID- 21094354
TI  - Safety and efficacy of sirolimus-eluting stent implantation in patients with
      acute coronary syndrome in the real world.
AB  - The use of drug-eluting stents in patients with acute coronary syndrome (ACS),
      particularly those with acute myocardial infarction (AMI), is controversial owing
      to concerns about late adverse events. We evaluated the long-term safety of
      sirolimus-eluting stent implantation in patients with ACS. Of 10,778 patients
      treated exclusively with a sirolimus-eluting stent in the j-Cypher registry, the
      3-year outcomes of 2,308 patients with ACS (953 patients with AMI) were compared
      to those of 8,470 patients without ACS. Compared to patients without ACS, the
      patients with ACS had a significantly greater adjusted risk of death or
      myocardial infarction (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.12
      to 1.37, p <0.0001) and definite or probable stent thrombosis (HR 1.43, 95% CI
      1.11 to 1.82, p = 0.006) within the first year after sirolimus-eluting stent
      implantation. However, after 1 year, patients with ACS no longer had a greater
      risk of death or myocardial infarction (HR 1.01, 95% CI 0.90 to 1.13, p = 0.87)
      and stent thrombosis (HR 1.32, 95% CI 0.92 to 1.86, p = 0.13). Of the patients
      with ACS, those with AMI had a greater risk of death or myocardial infarction (HR
      1.33, 95% CI 1.12 to 1.6, p = 0.001) and stent thrombosis (HR 1.57, 95% CI 1.05
      to 2.39, p = 0.03) than those with unstable angina pectoris within the first
      year. However, they had a similar risk of death or myocardial infarction (HR
      1.00, 95% CI 0.78 to 1.22, p = 0.83) and stent thrombosis (HR 0.83, 95% CI 0.38
      to 1.6, p = 0.59) after 1 year. The risk of late adverse events >1 year after
      sirolimus-eluting stent implantation was similar between those with and without
      ACS and between those with AMI and those with unstable angina pectoris.

PMID- 21094355
TI  - Tissue characterization of in-stent neointima using intravascular ultrasound
      radiofrequency data analysis.
AB  - Using virtual histology and intravascular ultrasound (VH-IVUS), tissue
      characterization of restenotic in-stent neointima after drug-eluting stent (DES)
      and bare metal stent (BMS) implantation was assessed. VH-IVUS was performed in
      117 lesions (70 treated with DESs and 47 treated with BMSs) with angiographic in
      stent restenosis and intimal hyperplasia (IH) > 50% of the stent area. The region
      of interest was placed between the luminal border and the inner border of the
      struts and tissue composition was reported as percentages of IH area (percent
      fibrous, percent fibrofatty, percent necrotic core, percent dense calcium) at the
      2 sites of maximal percent IH and maximal percent necrotic core. Mean follow-up
      times between stent implantation and VH-IVUS study were 43.5 +/- 33.8 months for
      BMS-treated lesions and 11.1 +/- 7.8 months for DES-treated lesions (p < 0.001).
      The 2 groups had greater percent necrotic core and percent dense calcium at
      maximal percent IH and maximal percent necrotic core sites, especially in stents
      that had been implanted for longer periods. In conclusion, this VH-IVUS analysis
      showed that BMS- and DES-treated lesions develop in-stent necrotic core and dense
      calcium, suggesting the development of in-stent neoatherosclerosis.

PMID- 21094356
TI  - Predictors of death and occurrence of appropriate implantable defibrillator
      therapies in patients with ischemic cardiomyopathy.
AB  - Most patients with chronic ischemia and an implantable cardiac defibrillator
      (ICD) for primary prevention do not experience therapies for ventricular
      arrhythmias on follow-up. The present study aimed to identify independent
      clinical, electrocardiographic, and echocardiographic predictors of death and
      occurrence of ICD therapy in patients with chronic ischemic cardiomyopathy and
      ICD for primary prevention. A total of 424 patients with chronic ischemic
      cardiomyopathy, ejection fraction <= 35%, and New York Heart Association (NYHA)
      class >= II were recruited. All patients underwent echocardiography before ICD
      insertion. Primary outcome was all-cause mortality; secondary outcome was
      occurrence of appropriate ICD therapy on follow-up. Primary and secondary
      outcomes occurred in 84 and 95 patients, respectively. Patients who died were
      more likely to have diabetes (hazard ratio [HR] 1.67, 95% confidence interval
      [CI] 1.00 to 2.79, p = 0.049), higher NYHA class (HR 1.96, 95% CI 1.15 to 3.33, p
      = 0.013), lower peri-infarct strain on echocardiogram (HR 1.25, 95% CI 1.07 to
      1.46, p = 0.005), and lower glomerular filtration rate (HR 1.01, 95% CI 1.00 to
      1.03, p = 0.022). Only peri-infarct strain (HR 1.22, 95% CI 1.09 to 1.36, p <
      0.001) predicted the occurrence of ICD therapy on follow-up. In conclusion, in
      chronic ischemic patients with an ICD for primary prevention, the presence of
      diabetes, renal dysfunction, higher NYHA class, and impaired peri-infarct zone
      function were predictors of all-cause mortality. In contrast, only impaired peri
      infarct zone function determined the occurrence of appropriate ICD therapy on
      follow-up.

PMID- 21094357
TI  - Comparison of prognostic usefulness (three years) of computed tomographic
      angiography versus 64-slice computed tomographic calcium scanner in subjects
      without significant coronary artery disease.
AB  - Coronary computerized tomographic angiography (CTA) has been used as a
      noninvasive method for ruling out high-grade stenoses. Even in the absence of
      such stenoses, analysis of coronary atherosclerosis may provide for important
      prognostic information, and this may be superior to exclusive coronary artery
      calcium scoring. We tested this hypothesis in patients undergoing CTA for
      clinical indications who had no stenoses requiring revascularization. From
      December 2004 to December 2006, 706 consecutive patients who underwent CTA but
      had no high-grade stenoses were included (58% men, mean age 59 +/- 11 years). CTA
      and coronary artery calcium scoring (Agatston method) were performed using a 64
      slice CT scanner with a gantry rotation time of 330 ms. CT angiograms were
      categorized as completely normal (group 1), showing minor plaque (group 2), or
      showing intermediate stenoses (group 3). Follow-up information was obtained in
      670 patients (95%) over a mean of 3.2 years. There were 31 major adverse events
      (5%), namely 9 deaths (all noncoronary), 2 myocardial infarctions, 5 strokes, 13
      coronary revascularization procedures (percutaneous or surgical > 6 months after
      CTA), and 2 peripheral percutaneous interventions. Coronary status as defined by
      CTA was predictive of major events after adjustment for age and gender. In group
      1, the probability of event-free survival at 3 years was 100%; in group 2, it was
      96%; and in group 3, it was 91%. Compared to group 1, the risk in group 2 was
      increased 2.3-fold, and in group 3, it was increased 5.6-fold after adjusting for
      age and gender. However, after addition of the coronary artery calcium score to
      the regression analysis, CT angiographic status no longer appeared to be
      predictive. In conclusion, the risk of a major adverse cardiovascular event or
      death increased in a graded manner with degree of coronary atherosclerosis as
      defined by CTA even in the absence of high-grade coronary stenoses. However, in
      the absence of high-grade stenoses, we were unable to demonstrate a superior
      prognostic value of CTA compared to coronary artery calcium.

PMID- 21094358
TI  - Electrocardiograms of menopausal women with coronary heart disease or at
      increased risk for its occurrence.
AB  - Little is known about electrocardiographic (ECG) characteristics of menopausal
      women with or at increased risk of coronary heart disease (CHD). Data from 10,101
      participants in the Raloxifene Use for The Heart (RUTH) trial were used to
      correlate baseline ECG abnormalities with clinical characteristics. Baseline
      characteristics that were statistically significantly associated (p <= 0.05) with
      ECG findings in univariate analyses were used to derive multivariate model
      selection. Of 59% normal electrocardiograms, 50% were from women with CHD and 69%
      from women at increased risk of CHD. In the women with CHD, 59% reported a
      previous myocardial infarction (MI); 43% had a normal electrocardiogram, and 49%
      had a definite ECG Q-wave MI. Women in the increased-risk group had not reported
      a previous MI, yet 11% had a definite ECG Q-wave MI. Of women reporting
      hypertension, 35% had ECG evidence of left ventricular hypertrophy, but 58% did
      not have an abnormal electrocardiogram. Significantly more women with diabetes in
      the increased-risk and documented CHD cohorts had abnormal electrocardiograms (p
      < 0.01 for the 2 cohorts). Percent abnormal electrocardiograms increased with
      increasing age (55 to 64, 65 to 74, and >= 75 years, p < 0.01) in all cohorts.
      Angina and coronary artery bypass graft surgery, but not percutaneous coronary
      intervention, predicted an abnormal electrocardiogram. In conclusion, there were
      high percentages of normal electrocardiograms in the increased-risk and
      documented CHD groups of RUTH participants, with substantial discrepancy between
      MI history and ECG MI documentation, and increasing age was the predominant
      correlate with an abnormal electrocardiogram in all 3 cohorts.

PMID- 21094359
TI  - Effect of central obesity, low high-density lipoprotein cholesterol and C
      reactive protein polymorphisms on C-reactive protein levels during treatment with
      Rosuvastatin (10 mg Daily).
AB  - Plasma levels of high-sensitivity C-reactive protein (hsCRP) are an important
      predictor of cardiovascular disease, and achievement of lower targets of hsCRP
      with rosuvastatin treatment was associated with improved cardiovascular outcomes.
      The aim of this study was to examine whether hsCRP levels were related to genetic
      variants and traditional cardiovascular risk factors in Chinese patients treated
      with rosuvastatin 10 mg/day. The relations were analyzed between on-treatment
      plasma hsCRP concentrations and cardiovascular risk factors and 14 single
      nucleotide polymorphisms in CRP and other candidate genes. In 281 patients with a
      median plasma hsCRP level of 0.81 mg/L (interquartile range 0.46 to 1.86), higher
      hsCRP levels were significantly associated with female gender, greater waist
      circumference (WC), having diabetes, higher triglycerides, and lower high-density
      lipoprotein (HDL) cholesterol. Three single-nucleotide polymorphisms (rs1205,
      3872G>A and rs2808630, 5237A>G in CRP and rs1169288, I27L in HNF1A) were
      independently associated with hsCRP levels before and after adjustment for other
      variables. WC and the CRP rs1205 polymorphism showed the strongest relations with
      hsCRP, and in multiple regression analysis, gender, WC, diabetes, triglycerides,
      HDL cholesterol, and the 3 genetic variants explained 35.5% of the variance in
      hsCRP levels. The 2 CRP polymorphisms, female gender, higher WC, and lower HDL
      cholesterol were associated with risk for having CRP concentrations >= 1 mg/L. In
      conclusion, central obesity, low HDL cholesterol, and CRP polymorphisms are major
      determinants of higher hsCRP levels in Chinese patients receiving treatment with
      rosuvastatin.

PMID- 21094360
TI  - Pharmacoepidemiology safety study of fibrate and statin concomitant therapy.
AB  - Combinations of statins and fibrates may be increasingly prescribed to achieve
      lipid goals in high-risk patients and those with other cardiovascular risk
      factors, such as mixed dyslipidemia. The purpose of this retrospective cohort
      study was to compare rates of hospitalization for specific diagnoses in a cohort
      of new users of statins or fibrates, using claims data from a large United States
      health insurer. New users of statin, fibrate, or statin-fibrate therapy from 2004
      to 2007 were identified; followed for hospitalization with rhabdomyolysis, renal
      impairment, hepatic injury, or pancreatitis; and confirmed by medical record
      review. Incidence rates (IRs) were compared across categories of fibrate or
      statin use, with adjusted IR ratios estimated using Poisson regression. A total
      of 584,784 patients initiated statins or fibrates. The IR of rhabdomyolysis in
      statins was 3.30 per 100,000 patient-years; the adjusted IR ratio for statin
      fenofibrate combinations compared to statins alone was 3.75 (95% confidence
      interval 1.23 to 11.40). The IRs of renal impairment and pancreatitis in statins
      were 108.87 per 100,000 patient-years and 45.76 per 100,000 patient-years,
      respectively; the adjusted IR ratios for statin-fenofibrate combinations compared
      to statins alone were 1.47 (95% confidence interval 1.12 to 1.93) and 2.87 (95%
      confidence interval 2.05 to 4.02), respectively. The IR of hepatic injury with
      statins was 8.57 per 100,000 patient-years, with no risk difference between
      exposure groups. In conclusion, the risk for rhabdomyolysis was low, although
      higher in patients newly treated with statin-fibrate concurrent therapy than
      those treated with either as monotherapy. The risk for pancreatitis was higher in
      patients treated with fenofibrate, whether in combination with statins or alone.

PMID- 21094361
TI  - Cardiovascular risk in patients with fasting blood glucose levels within normal
      range.
AB  - Fasting glucose levels elevated beyond the normal range have been associated with
      increased cardiovascular risk. However, it is unknown whether this association
      exists for variations of fasting glucose within the normal range. The present
      study was conducted using the computerized database of the Sharon-Shomron
      District of Clalit Health Services. Included in the present study were subjects
      with fasting glucose levels within the normal range (< 100 mg/dl). We excluded
      patients with a history of cardiovascular disease or diabetes. The primary
      outcome was the incidence of coronary revascularization with either percutaneous
      coronary intervention or coronary artery bypass grafting. The 28,263 participants
      (age 53.7 +/- 12.2 years) were divided into quartiles according to the fasting
      glucose level (75.4 +/- 4.5, 83.6 +/- 1.7, 88.9 +/- 1.4, and 95.1 +/- 2.2 mg/dl).
      During a mean follow-up of 5.9 +/- 0.7 years, 424 subjects required coronary
      revascularization. A progressive increase was seen in the risk of coronary
      revascularization as the fasting glucose levels increased within the normal range
      (hazard ratio 1.73, 95% confidence interval 1.3 to 2.3, p > 0.001, between the
      fourth and first quartiles). However, this association lost its statistical
      significance after adjustments for the conventional coronary risk factors (hazard
      ratio 1.17, 95% confidence interval 0.85 to 1.62, p = 0.328). In conclusion,
      elevated fasting glucose levels within the normal range were associated with an
      increased cardiovascular risk. This association was caused by the greater
      prevalence of the other conventional risk factors and not by the glucose level
      itself.

PMID- 21094363
TI  - Atrial substrate properties and outcome of catheter ablation in patients with
      paroxysmal atrial fibrillation associated with diabetes mellitus or impaired
      fasting glucose.
AB  - Diabetes mellitus has been reported to be an independent risk factor of atrial
      fibrillation (AF). The present study investigated the atrial substrate properties
      and clinical outcome of catheter ablation in patients with paroxysmal AF and
      abnormal glucose metabolism. A total of 228 patients with paroxysmal AF who had
      undergone catheter ablation for the first time were enrolled. An abnormal glucose
      metabolism (n = 65) was defined as diabetes mellitus or an impaired fasting
      glucose. We analyzed the clinical and electrophysiologic characteristics in, and
      the clinical outcome of, patients with AF with and without an abnormal glucose
      metabolism. The right atrial (107.2 +/- 15.4 vs 96.0 +/- 16.5 ms, p < 0.001) and
      left atrial (108.4 +/- 22.3 vs 94.0 +/- 17.5 ms, p < 0.001) total activation
      times were significantly longer in the patients with AF and an abnormal glucose
      metabolism than in those without an abnormal metabolism. Furthermore, the right
      atrial (1.46 +/- 0.61 vs 2.00 +/- 0.70 mV, p < 0.001) and left atrial (1.48 +/-
      0.74 vs 2.05 +/- 0.78 mV, p < 0.001) bipolar voltages were significantly lower in
      those with AF and an abnormal glucose metabolism than in those without. The AF
      recurrence rate was also greater in the patients with an abnormal glucose
      metabolism (18.5% vs 8.0%, p = 0.022) than in those without. The follow-up
      duration was 18.8 +/- 6.4 months. In conclusion, an abnormal glucose metabolism
      affects the biatrial substrate properties with an intra-atrial conduction delay,
      decreased voltage, and greater recurrence rate after catheter ablation.

PMID- 21094362
TI  - Effect of combined spironolactone-beta-blocker +/- enalapril treatment on
      occurrence of symptomatic atrial fibrillation episodes in patients with a history
      of paroxysmal atrial fibrillation (SPIR-AF study).
AB  - Angiotensin II and aldosterone are key factors responsible for the structural and
      neurohormonal remodeling of the atria and ventricles in patients with atrial
      fibrillation (AF). The aim of the present study was to evaluate the
      antiarrhythmic effects of spironolactone compared to angiotensin-converting
      enzyme inhibitors in patients with recurrent AF. A cohort of 164 consecutive
      patients (mean age 66 years, 87 men), with an average 4-year history of recurrent
      AF episodes, was enrolled in a prospective, randomized, 12-month trial with 4
      treatment arms: group A, spironolactone, enalapril, and a beta blocker; group B,
      spironolactone and a beta blocker; group C, enalapril plus a beta blocker; and
      group D, a beta blocker alone. The primary end point of the trial was the
      presence of symptomatic AF episodes documented on the electrocardiogram. At 3-, 6
      , 9-, and 12 months, a significant (p < 0.001) reduction had occurred in the
      incidence of AF episodes in both spironolactone-treated groups (group A,
      spironolactone, enalapril, and a beta blocker; and group B, spironolactone plus a
      beta blocker) compared to the incidence in patients treated with enalapril and a
      beta blocker (group C) or a beta blocker alone (group D). No significant
      difference was seen in AF recurrences between patients taking spironolactone and
      a beta blocker with (group A) and without (group B) enalapril. No significant
      differences were found in the systolic or diastolic blood pressure or heart rate
      among the groups before and after 1 year of follow-up. In conclusion, combined
      spironolactone plus beta-blocker treatment might be a simple and valuable option
      in preventing AF episodes in patients with normal left ventricular function and a
      history of refractory paroxysmal AF.

PMID- 21094364
TI  - Comparison of muscle functional electrical stimulation to conventional bicycle
      exercise on endothelium and functional status indices in patients with heart
      failure.
AB  - The aim of this prospective, open-label, cohort study was to compare the effect
      of muscle functional electrical stimulation (FES) on endothelial function to that
      of conventional bicycle training. Eligible patients were those with New York
      Heart Association class II or III heart failure symptoms and ejection fractions
      <= 0.35. Two physical conditioning programs were delivered: FES of the muscles of
      the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week
      washout period between them. Brachial artery flow-mediated dilation (FMD) and
      other parameters were assessed before and after FES and the bicycle training
      program. FES resulted in a significant improvement in FMD, which increased from
      5.9 +/- 0.5% to 7.7 +/- 0.5% (95% confidence interval for the difference 1.5% to
      2.3%, p < 0.001). Bicycle training also resulted in a substantial improvement of
      endothelial function. FMD increased from 6.2 +/- 0.4% to 9.2 +/- 0.4% (95%
      confidence interval for the difference 2.5% to 3.5%, p < 0.001). FES was
      associated with a 41% relative increase in FMD, compared to 57% with bicycle
      exercise (95% confidence interval for the difference between the relative changes
      1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD
      value after bicycle training compared to FES (9.2 +/- 0.4% vs 7.7 +/- 0.5%, p <
      0.001). In conclusion, the effect of muscle FES in patients with heart failure on
      endothelial function, although not equivalent to that of conventional exercise,
      is substantial. Muscle FES protocols may prove very useful in the treatment of
      patients with heart failure who cannot or will not adhere to conventional
      exercise programs.

PMID- 21094365
TI  - Long-term risk of aortic events following aortic valve replacement in patients
      with bicuspid aortic valves.
AB  - Bicuspid aortic valve (BAV) is associated with ascending aortopathy predisposing
      to aneurysmal dilatation and dissection, even after successful aortic valve
      replacement (AVR). There is, however, scant evidence on which to make
      recommendations for prophylactic replacement of the ascending aorta at the time
      of AVR. The medical records of patients who underwent AVR for BAV without aortic
      replacement or repair from 1960 to 1995 were reviewed. Follow-up was by review of
      the medical record and postal questionnaire. Among 1,286 patients, the mean age
      at operation was 58 +/- 14 years. During the follow-up interval (median 12 years,
      range 0 to 38), there were 13 documented aortic dissections (1%), 11 ascending
      aortic replacements (0.9%), and 127 documented cases of progressive aortic
      enlargement (9.9%). Fifteen-year freedom from aortic dissection, enlargement, or
      replacement was 89% (95% confidence interval [CI] 87% to 91%) and was lower in
      patients with documented aortic enlargement at the time of AVR (85%, 95% CI 81%
      to 89%) compared to those whose aortic dimensions were normal (93%, 95% CI 90% to
      96%) (p = 0.001). Multivariate predictors of aortic complications included
      interval (subsequent) AVR (hazard ratio [HR] 3.5, 95% CI 2.3 to 5.4, p <0.001),
      concomitant coronary artery bypass grafting (HR 2.6, 95% CI 1.7 to 4.0, p
      <0.001), enlarged aorta (HR 1.8, 95% CI 1.3 to 2.6, p = 0.001), and history of
      tobacco abuse (HR 1.8, 95% CI 1.2 to 2.6, p = 0.003). Aortic dilatation did not
      predict mortality. In conclusion, despite a true risk for aortic events after AVR
      for BAV, the occurrence of aortic dissection was low. Any incremental surgical
      risk imposed by prophylactic replacement of the ascending aorta must be equally
      low.

PMID- 21094366
TI  - Impact of baseline severity of aortic valve stenosis on effect of intensive lipid
      lowering therapy (from the SEAS study).
AB  - Retrospective studies have suggested a beneficial effect of lipid-lowering
      treatment on the progression of aortic stenosis (AS) in milder stages of the
      disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in
      Aortic Stenosis (SEAS) study, 4.3 years of combined treatment with simvastatin 40
      mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic
      cardiovascular events (ICEs) were significantly reduced in the overall study
      population. However, the impact of baseline AS severity on treatment effect has
      not been reported. Baseline and outcomes data in 1,763 SEAS patients (mean age 67
      years, 39% women) were used. The study population was divided into tertiles of
      baseline peak aortic jet velocity (tertile 1: <= 2.8 m/s; tertile 2: > 2.8 to 3.3
      m/s; tertile 3: > 3.3 m/s). Treatment effect and interaction were tested in Cox
      regression analyses. The rates of AVEs and ICEs increased with increasing
      baseline severity of AS. In Cox regression analyses, higher baseline peak aortic
      jet velocity predicted higher rates of AVEs and ICEs in all tertiles (all p
      values < 0.05) and in the total study population (p < 0.001). Simvastatin
      ezetimibe treatment was not associated with a statistically significant reduction
      in AVEs in any individual tertile. A significant quantitative interaction between
      the severity of AS and simvastatin-ezetimibe treatment effect was demonstrated
      for ICEs (p < 0.05) but not for AVEs (p = 0.10). In conclusion, the SEAS study
      results demonstrate a strong relation between baseline the severity of AS and the
      rate of cardiovascular events but no significant effect of lipid-lowering
      treatment on AVEs, even in the group with the mildest AS.

PMID- 21094367
TI  - Effect of implantable cardioverter-defibrillator on left ventricular ejection
      fraction in patients with idiopathic dilated cardiomyopathy.
AB  - Current guidelines have indicated an implantable cardioverter-defibrillator (ICD)
      for patients with severe idiopathic dilated cardiomyopathy, for both primary and
      secondary prevention. Compared to coronary artery disease, the overall benefit
      has been smaller. A more refined risk assessment, using the left ventricular
      ejection fraction (LVEF) and prevention mode (primary/secondary), is still needed
      to guide ICD implantation. Patients included in 2 large ICD registers were
      analyzed regarding the appropriate therapies and improvement of LVEF, overall and
      in subgroups of prevention mode and LVEF < 20% versus > 20%. Overall, 349
      patients were included; 70% were men, the mean age was 54 years, and the mean
      follow-up was 33 months. Cardiac resynchronization therapy (CRT) was used in 57%,
      and secondary prevention was present in 30%. ICD therapies were delivered to 33%
      of the patients, in most for ventricular tachycardia. Patients receiving an ICD
      for secondary prevention and non-CRT were more likely to have arrhythmic events
      (both p < 0.05). The cumulative event rates at 5 years were 53% for secondary and
      33% for primary prevention (p < 0.001). Depending on the prevention mode and LVEF
      status (< 20% vs > 20%), the event rates ranged from 30% to 76%. The mean LVEF
      improved by 10%, independently of the stimulation mode (CRT 22% to 31%, non-CRT
      26% to 35%; p < 0.0001). A persistent improvement to > 35% was seen in only 25%
      of CRT patients but in 45% of non-CRT patients (p = 0.004). In conclusion, the
      results from the present study have demonstrated that in patients with idiopathic
      dilated cardiomyopathy, the potential for LVEF improvement is considerable and
      that the rate of ICD interventions strongly depends on the prevention mode and
      LVEF. These findings could be the basis for additional risk stratification tools.

PMID- 21094368
TI  - Axillary versus infraclavicular placement for endocardial heart rhythm devices in
      patients with pediatric and congenital heart disease.
AB  - Our objective was to evaluate the implant and mid-term outcomes of transvenous
      pacemaker or internal cardioverter-defibrillator placement by alternative
      axillary approaches compared to the infraclavicular approach in a pediatric and
      congenital heart disease population. We conducted a retrospective review of all
      patients with new endocardial heart rhythm devices placed at 4 pediatric
      arrhythmia centers. A total of 317 patients were included, 63 had undergone a 2
      incision axillary approach, 51 a retropectoral axillary approach, and 203 an
      infraclavicular approach. Congenital heart disease was present in 62% of the
      patients. The patients with the 2-incision axillary approach were younger and
      smaller. The patients with the retropectoral axillary approach were less likely
      to have undergone previous cardiac surgery and were more likely to have had an
      internal cardioverter-defibrillator placed. The duration of follow-up was 2.4 +/-
      1.9 years for the 2-incision axillary, 2.6 +/- 2.6 years for retropectoral
      axillary, and 3.5 +/- 1.4 years for the infraclavicular technique (p = 0.01). No
      differences were seen in implant characteristics, lead longevity, implant
      complications, lead fractures or dislodgements, inappropriate internal
      cardioverter-defibrillator discharges, or device infections among the 3 groups.
      In conclusion, our data support that the outcomes of axillary approaches are
      comparable to the infraclavicular approach for endocardial heart rhythm device
      placement and that axillary approaches should be considered a viable option in
      patients with pediatric and congenital heart disease.

PMID- 21094369
TI  - Relation of size of secondary ventricles to exercise performance in children
      after fontan operation.
AB  - The effects of the nondominant or secondary ventricle on the Fontan circulation
      are not known. The present study used cardiac magnetic resonance imaging to
      investigate the relations between secondary ventricular size and global cardiac
      performance. The Fontan cross-sectional study collected data from 7 centers
      participating in the Pediatric Heart Network. Subjects with complete cardiac
      magnetic resonance imaging data and an identifiable secondary ventricle were
      included in the analysis. Relationships between body surface area-adjusted
      parameters of the secondary ventricle (mass, end-diastolic volume, mass/volume
      ratio, and stroke volume) and the following measures were assessed. These
      measures included the percentage of predicted peak oxygen consumption and oxygen
      consumption at the ventilatory anaerobic threshold, ejection fraction of the main
      ventricular chamber, echocardiographic diastolic function grade, serum B-type
      natriuretic peptide, primary ventricular end-diastolic pressure, and parent
      reported physical functioning summary score on the Child Health Questionnaire. Of
      the 546 enrolled subjects, 123 (age 12.1 +/- 3.3 years, 56% male) had undergone
      cardiac magnetic resonance imaging, and 38 had achieved maximal aerobic capacity.
      A larger secondary ventricular end-diastolic volume, lower mass/volume ratio, and
      greater secondary/total ventricular stroke volume ratio were associated with a
      greater exercise capacity. No significant relationships were found between the
      measures of the secondary ventricle and the other outcomes. In conclusion, in
      children after the Fontan operation, a larger and less hypertrophied secondary
      ventricle with a greater contribution to stroke volume was associated with a
      better exercise capacity.

PMID- 21094370
TI  - Can echocardiographic evaluation of cardiopulmonary hemodynamics decrease right
      heart catheterizations in end-stage heart failure patients awaiting
      transplantation?
AB  - Candidacy for heart transplantation is influenced by the severity of pulmonary
      hypertension. In this study, invasive hemodynamics from right-sided cardiac
      catheterization were compared with values obtained by validated equations from
      Doppler 2-dimensional transthoracic echocardiography. This prospective study was
      conducted in 40 patients with end-stage heart failure evaluated for heart
      transplantation or ventricular assist device implantation. Transthoracic
      echocardiography and right-sided cardiac catheterization were performed within 4
      hours. From continuous-wave Doppler of the tricuspid regurgitation jet, pulmonary
      artery systolic pressure was calculated as the peak gradient across the tricuspid
      valve plus right atrial pressure estimated from inferior vena cava filling. Mean
      pulmonary artery pressure was calculated as (0.61 * pulmonary artery systolic
      pressure) + 2. Pulmonary vascular resistance (PVR) was calculated as (tricuspid
      regurgitation velocity/right ventricular outflow tract time-velocity integral *
      10) + 0.16. Pulmonary capillary wedge pressure was calculated as 1.91 + (1.24 *
      E/E'). Pearson's correlation and Bland-Altman analysis of mean differences
      between echocardiographic and right-sided cardiac catheterization measurements
      were statistically significant for all hemodynamic parameters (pulmonary artery
      systolic pressure: r = 0.82, p < 0.05, mean difference 3.1 mm Hg, 95% confidence
      interval [CI] -0.2 to 6.3; mean pulmonary artery pressure: r = 0.80, p < 0.05,
      mean difference 2.5 mm Hg, 95% CI 0.3 to 4.6; PVR: r = 0.52, p < 0.05, mean
      difference 0.8 Wood units, 95% CI 0.3 to 1.4; pulmonary capillary wedge pressure:
      r = 0.65, p < 0.05, mean difference 2.2 mm Hg, 95% CI 0.1 to 4.3). Compared with
      right-sided cardiac catheterization, PVR by Doppler echocardiography identified
      all patients with PVR > 4 Wood units (n = 4), 73% of patients with PVR <2 Wood
      units (n = 8), and 52% of patients with PVR from 2 to 4 Wood units (n = 10). In
      conclusion, echocardiographic estimation of cardiopulmonary hemodynamics is
      reliable in patients with end-stage cardiomyopathy. The noninvasive assessment of
      hemodynamics by echocardiography may be able to decrease the number of serial
      right-sided cardiac catheterizations in selected patients awaiting heart
      transplantation. However, in patients with borderline PVR, right-sided cardiac
      catheterization is indicated to assess eligibility for transplantation.

PMID- 21094371
TI  - Effect of a standardized quality-improvement protocol on radiation dose in
      coronary computed tomographic angiography.
AB  - Coronary computed tomographic angiography (CCTA) is associated with ionizing
      radiation, prompting concerns of future cancer risk. Recent studies have reported
      reduced radiation doses and similar image quality by the selective use of dose
      reduction techniques, although the clinical penetration of these methods has been
      limited. In a quality improvement initiative, a comprehensive, standardized
      radiation dose reduction protocol was implemented, and its effect on radiation
      dose and image quality was assessed. A total of 449 patients who underwent 64
      detector CCTA at 3 centers were prospectively evaluated, and patients were
      compared before (n = 247) and after (n = 202) the implementation of a
      standardized body mass index-based and heart rate-based protocol that
      simultaneously incorporated multiple dose reduction strategies. Median radiation
      dose decreased from 2.6 mSv (interquartile range 2.0 to 4.2) to 1.3 mSv
      (interquartile range 0.8 to 1.9) after the implementation of the standardized
      protocol (p < 0.001). On multivariate analysis, reduction in overall radiation
      dose was observed by numerous dose reduction techniques, with varying efficacy of
      dose lowering: prospective (vs retrospective) electrocardiographic gating (-82%),
      reduced tube voltage (-41% for 100 vs 120 kV), lower tube current (-25% per -100
      mA), and reduced overall scan length (-6% per -1 cm) (p < 0.001 for each). No
      differences were observed between patients before and after the initiation of the
      protocol for study interpretability (96% vs 96%, p = 0.66). There was an increase
      in signal-to-noise ratio after implementing the standardized protocol (11 +/- 3
      vs 12 +/- 4, p < 0.01). In conclusion, a quality improvement protocol for CCTA
      incorporating multiple dose reduction techniques permits significant radiation
      dose reduction and may improve the safety profile of CCTA.

PMID- 21094372
TI  - Effect of amiodarone-induced hyperthyroidism on left ventricular outflow
      obstruction after septal myectomy for hypertrophic cardiomyopathy.
AB  - Patients with obstructive hypertrophic cardiomyopathy who undergo septal myectomy
      are at risk for developing postoperative atrial fibrillation. Amiodarone is
      effective in treating this arrhythmia but is associated with multiple adverse
      effects, often with delayed onset. A novel case is described of a patient who
      developed type 2 amiodarone-induced hyperthyroidism that presented as recurrence
      of outflow obstruction after septal myectomy. The patient's symptoms and
      echocardiographic findings of outflow obstruction resolved substantially with the
      treatment of the amiodarone-induced hyperthyroidism. Amiodarone-induced
      hyperthyroidism of delayed onset can be a subtle diagnosis, requiring a high
      index of suspicion. In conclusion, recognition of this diagnosis in patients with
      recurrence of outflow obstruction by symptoms and cardiac imaging after septal
      myectomy may avoid unnecessary repeat surgical intervention.

PMID- 21094373
TI  - Folic Acid as a cardiovascular drug: dose matters.

PMID- 21094374
TI  - The "obesity paradox" in coronary heart disease.

PMID- 21094375
TI  - Vitamin D deficiency and stroke: time to act!

PMID- 21094376
TI  - Alignment of high resolution magic angle spinning magnetic resonance spectra
      using warping methods.
AB  - The peaks of magnetic resonance (MR) spectra can be shifted due to variations in
      physiological and experimental conditions, and correcting for misaligned peaks is
      an important part of data processing prior to multivariate analysis. In this
      paper, five warping algorithms (icoshift, COW, fastpa, VPdtw and PTW) are
      compared for their feasibility in aligning spectral peaks in three sets of high
      resolution magic angle spinning (HR-MAS) MR spectra with different degrees of
      misalignments, and their merits are discussed. In addition, extraction of
      information that might be present in the shifts is examined, both for simulated
      data and the real MR spectra. The generic evaluation methodology employs a number
      of frequently used quality criteria for evaluation of the alignments, together
      with PLS-DA to assess the influence of alignment on the classification outcome.
      Peak alignment greatly improved the internal similarity of the data sets.
      Especially icoshift and COW seem suitable for aligning HR-MAS MR spectra,
      possibly because they perform alignment segment-wise. The choice of reference
      spectrum can influence the alignment result, and it is advisable to test several
      references. Information from the peak shifts was extracted, and in one case
      cancer samples were successfully discriminated from normal tissue based on shift
      information only. Based on these findings, general recommendations for alignment
      of HR-MAS MRS data are presented. Where possible, observations are generalized to
      other data types (e.g. chromatographic data).

PMID- 21094377
TI  - Review: Aptamers in microfluidic chips.
AB  - This review, covering reports published from 2002 to August 2010, shows how
      aptamers have made significant contributions in the improvements of microfluidic
      chips for affinity extraction, separations and detections. Furthermore,
      microfluidic chip methods for studying aptamer-target interactions and performing
      aptamer selections have also been summarized. Accordingly, research vacancies and
      future development trends in these areas are discussed.

PMID- 21094378
TI  - Bioanalytical methods for determination of tamoxifen and its phase I metabolites:
      a review.
AB  - The selective estrogen receptor modulator tamoxifen is used in the treatment of
      early and advanced breast cancer and in selected cases for breast cancer
      prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin
      containing monooxygenase are responsible for the extensive metabolism of
      tamoxifen into several phase I metabolites that vary in toxicity and potencies
      towards estrogen receptor (ER) alpha and ER beta. An extensive overview of
      publications on the determination of tamoxifen and its phase I metabolites in
      biological samples is presented. In these publications techniques were used such
      as capillary electrophoresis, liquid, gas and thin layer chromatography coupled
      with various detection techniques (mass spectrometry, ultraviolet or fluorescence
      detection, liquid scintillation counting and nuclear magnetic resonance
      spectroscopy). A trend is seen towards the use of liquid chromatography coupled
      to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for
      identification of unknown metabolites and quantification of known metabolites
      reaching lower limit of quantification levels in the sub pg mL(-1) range.
      Although tamoxifen is also metabolized into phase II metabolites, the number of
      publications reporting on phase II metabolism of tamoxifen is scarce. Therefore
      the focus of this review is on phase I metabolites of tamoxifen. We conclude that
      in the past decades tamoxifen metabolism has been studied extensively and
      numerous metabolites have been identified. Assays have been developed for both
      the identification and quantification of tamoxifen and its metabolites in an
      array of biological samples. This review can be used as a resource for method
      transfer and development of analytical methods used to support pharmacokinetic
      and pharmacodynamic studies of tamoxifen and its phase I metabolites.

PMID- 21094379
TI  - Recent developments in on-line electrochemical stripping analysis--an overview of
      the last 12 years.
AB  - This paper presents an overview of the field of electrochemical stripping
      analysis in flow systems covering developments in the last 12 years (since 1998).
      The review discusses the flow schemes utilized in stripping analysis, techniques
      for on-line sample pre-treatment, the main pre-concentration and
      stripping/detection modes, the most important flow-through cell configurations
      used and the different types of working electrodes. Finally, applications in
      inorganic and organic analysis are discussed. Special emphasis is given to
      different novel approaches developed over the last few years that hold some
      promise for the future such as the use of the lab-on-a valve (LOV) configuration,
      microfluidic manifolds, flow-probes for remote sensing, environmentally friendly
      electrode materials and hyphenation with spectroscopic techniques.

PMID- 21094380
TI  - Spectrochemical study for the in situ detection of oil spill residues using laser
      induced breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been used to identify the
      differences or similarities between crude oil and fuel residues. Firstly, a man
      portable LIBS analyzer was used for the on-site environmental control and
      analysis of the oil spill from The Prestige. An exhaustive analysis of crude oil
      and oil spill residues (collected during the field campaign in the Galician
      Coast) was performed in the laboratory. Characteristics elements in petroleum
      such as C, H, N, O, Mg, Na, Fe and V were detected. In addition, contributions
      from Ca, Si and Al in the composition of residues have been found. The use of
      intensity ratios of line and band emissions in the original fuel (crude oil) and
      in the aged residues allowed a better characterization of the samples than the
      simple use of peak intensities. The chemical composition between the crude oil
      and the fuel residues was found completely different. As well, a statistical
      method was employed in order to discriminate residues. Although significant
      differences were observed, no conclusions in terms of age and provenance could be
      reached due to the unknowledgment in the origin of the samples.

PMID- 21094381
TI  - Study of the binding equilibrium between Zn(II) and HSA by capillary
      electrophoresis-inductively coupled plasma optical emission spectrometry.
AB  - A new method has been developed for following the interaction between zinc ion
      and human serum albumin (HSA) by capillary electrophoresis-inductively coupled
      plasma optical emission spectrometry. Under optimized experimental conditions,
      the detection limit (3sigma) for free Zn(2+) ion was found to be 1.34 MUM by
      running 11 replicates of the reagent blank. The RSD was less than 3% and the
      recovery was more than 98.13%. The linear range of zinc ion concentration was
      between 5.1 MUM and 0.3M. The measured Zn(II)-HSA combination values of n(1) and
      K(1) for primary binding of Zn(2+) to HSA were 1.09 and 2.29*10(5) L mol(-1),
      respectively. The measured values of n(2) and K(2) for the non-specific binding
      of Zn(2+) to HSA were 8.96 and 6.65*10(3) L mol(-1), respectively. This new
      method allows rapid analysis of a small amount of sample, simple operation, while
      avoiding long periods of dialysis and eliminating interference from other metal
      ions. This method provides a reliable and convenient new way for studying
      interactions between metal ions and biomolecules.

PMID- 21094382
TI  - Asymmetric least squares for multiple spectra baseline correction.
AB  - In this paper, based on asymmetric least squares smoothing, a new algorithm for
      multiple spectra baseline correction is proposed. By means of the similarity
      among the multiple spectra, the algorithm estimates the baselines by penalizing
      the differences in the baseline corrected signals, which makes the algorithm
      possible to eliminate scatter effects on the spectra. In addition, a relaxation
      factor which measures the similarity of the baseline corrected spectra is
      incorporated into the optimization model and an alternate iteration strategy is
      used to solve the optimization problem. The proposed algorithm is fast and can
      output multiple baselines simultaneously. Experimental results on both simulated
      data and real data demonstrate the effectiveness and efficiency of the algorithm.

PMID- 21094383
TI  - Spectrometric study of the folding process of i-motif-forming DNA sequences
      upstream of the c-kit transcription initiation site.
AB  - The c-kit oncogene shows a cytosine-rich DNA region upstream of the transcription
      initiation site which forms an i-motif structure at slightly acidic pH values
      (Bucek et al. [5]). In the present study, the pH-induced formation of i-motif -
      forming sequences 5'-CCC CTC CCT CGC GCC CGC CCG-3' (ckitC1, native), 5'-CCC TTC
      CCT TGT GCC CGC CCG-3' (ckitC2) and 5'-CCCTT CCC TTTTT CCC T CCC T-3' (ckitC3)
      was studied by spectroscopic techniques, such as UV molecular absorption and
      circular dichroism (CD), in tandem with two multivariate data analysis methods,
      the hard modelling-based matrix method and the soft modelling-based MCR-ALS
      approach. Use of the hard chemical modelling enabled us to propose the
      equilibrium model, which describes spectral changes as functions of solution
      acidity. Additionally, the intrinsic protonation constant, K(in), and the
      cooperativity parameters, omega(c), and omega(a), were calculated from the
      fitting procedure of the coupled CD and molecular absorption spectra. In the case
      of ckitC2 and ckitC3, the hard model correctly reproduced the spectral variations
      observed experimentally. The results indicated that folding was accompanied by a
      cooperative process, i.e. the enhancement of protonated structure stability upon
      protonation. In contrast, unfolding was accompanied by an anticooperative
      process. Finally, folding of the native sequence, ckitC1, seemed to follow a more
      complex mechanism.

PMID- 21094384
TI  - Uncertainty of measurement for summed masses: application to controlled
      substances.
AB  - Because sentences for drug possession depend on the mass of the seized drug,
      testing laboratories must often determine the summed mass of numerous items
      submitted under a single case. One common practice for this purpose is to
      continue analyzing and weighing samples until a legal threshold is passed, at
      which point it is important to inform the court whether the summed mass is
      significantly above the threshold, or only marginally so. This paper develops a
      means for estimating the uncertainty of the summed mass for the common situation
      where the readability, d, of the balance dominates the uncertainty. It is seen
      that for all sample sizes the uncertainty, UM, is given by the remarkable simple
      expression UM=(d/2)*[N+SQRT(3N)]+N*CCE, where N is the number of items and CCE is
      the absolute value of the calibration check error. In most instances, this can be
      further simplified to UM=N*d.

PMID- 21094385
TI  - Comparing the weathering patterns of six oils using 3-way generalized Procrustes
      rotation and matrix-augmentation principal components.
AB  - A case study is presented in which advanced chemical fingerprinting and data
      interpretation techniques are used to characterize and compare the weathering
      processes of six oil spillages made under controlled conditions (including the
      heavy oil released after the Prestige tanker sunk off the Galician coast-NW Spain
      on 2002). A tiered analytical approach using gas chromatography-flame ionization
      detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) was applied
      along with two different approaches for 3-way analyses; namely, generalized
      Procrustes rotation, and matrix-augmented principal components analysis. Results
      showed that the two 3-way chemometric techniques leaded to essentially the same
      conclusions when analyzing three sets of compounds fingerprinting the spilled
      hydrocarbons (aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAHs) and
      a set of diagnostic ratios). A steady evolution on the weathering of the oils was
      observed with both techniques, but for the diagnostic ratios. The variables
      involved on the weathering were the lightest aliphatic hydrocarbons and a general
      combination of the PAHs, which differentiated mostly among the light and the
      heavy products (fuel oils).

PMID- 21094386
TI  - Potentiometric determination of coextraction constants of potassium salts in ion
      selective electrodes utilizing a nitrobenzene liquid membrane phase.
AB  - A theoretical treatment of potentiometric data is applied to calculate
      coextraction constants (K(IA)) for three potassium salts from water into a liquid
      nitrobenzene phase. The experiment involves treating nitrobenzene as a membrane
      and contacting it with two aqueous solutions of different ion activities. In the
      presence of either a cation or anion exchanger, the ratio of activities of ions
      in the two aqueous phases gives rise to a potential difference across the
      membrane that depends upon the nature and charge of the counter ion of the ion
      exchanger in excess. Here, the cation exchanger was chosen to be potassium
      tetrakis(4-chlorophenyl)borate (KTpClPB) and the anion exchanger was
      tetradodecylammonium chloride (TDDACl). TDDACl was incrementally added to the
      nitrobenzene phase containing a fixed concentration of KTpClPB, and the
      corresponding emf was recorded as a function of concentration of TDDACl. The
      membrane changes from one with cation exchanger properties (excess KTpClPB) to
      one with anion exchanger properties (excess TDDACl). The potential difference and
      shape of the titration curve can be predicted by theory based on the phase
      boundary potential model. Log(K(IA)) values calculated for KCl, KNO(3) and
      KClO(4) in nitrobenzene were found as: -10.53 (+/- 0.09), -8.16 (+/- 0.05) and 
      5.63 (+/- 0.03) respectively, in accordance with the Hofmeister series of
      lipophilicity, and similar to those observed in PVC membranes containing other
      plasticizers. The method presented here offers the advantage over other methods
      to calculate K(IA), in that it is relatively experimentally simple without
      compromising the accuracy of the calculated coextraction constants. The ability
      to titrate directly into the liquid membrane phase affords a higher precision
      compared to the preparation of a series of PVC/plasticizer membranes with
      different compositions.

PMID- 21094387
TI  - Innovative chemically bonded ionic liquids-based sol-gel coatings as highly
      porous, stable and selective stationary phases for solid phase microextraction.
AB  - In this work, two allyl-functionalised ionic liquids (ILs), 1-allyl-3
      methylimidazolium hexafluorophosphate and 1-allyl-3-methylimidazolium
      bis(trifluoromethanesulphonyl)imide, were used as selective coating materials to
      prepare chemically bonded ILs-based organic-inorganic hybrid solid phase
      microextraction fibres. These fibres were prepared with the aid of gamma
      methacryloxypropyltrimethoxysilane as bridge using sol-gel method and free
      radical cross-linking technology. The underlying mechanisms of the sol-gel
      reaction were proposed, and the successful binding of these functional ILs to the
      sol-gel substrate was confirmed by Fourier transform infrared spectroscopy. These
      IL-based sol-gel coatings had porous surface structure, high thermal stability, a
      wide range of pH stability, strong solvent resistance and good coating
      preparation reproducibility. They also had high selectivity and sensitivity
      towards strong polar phenolic environmental estrogens (PEEs) and aromatic amines
      due to the strong electrostatic interactions, hydrogen bonding and pi-pi
      interactions provided by the special molecular structure of these imidazolium
      ILs. Moreover, their characteristics were somewhat different depending on the
      type of anions in the IL structure. The practical applicability of these IL-based
      sol-gel coatings was evaluated through the analysis of PEEs in two real water
      samples. The detection limits were quite low, varying from 0.0030 to 0.1248 MUgL(
      1). The linearity was very good in the range of 0.1 to 1000 MUgL(-1) for most
      analytes, and the relative standard deviation values were below 6%. The relative
      recoveries were between 83.1 and 104.1% for lake water and between 89.1 and 97.1%
      for sewage drainage outlet water.

PMID- 21094388
TI  - Use of Saccharomyces cerevisiae immobilized in agarose gel as a binding agent for
      diffusive gradients in thin films.
AB  - A new binding agent, consisting of the yeast Saccharomyces cerevisiae immobilized
      in agarose, is proposed for use in diffusive gradients in thin films (DGT).
      Different gel compositions, containing from 4.5% to 20% (m/v) of S. cerevisiae
      and 1.5-5.0% (m/v) of agarose, were prepared and tested for uptake of Cd(II). For
      gels containing 20% (m/v) of S. cerevisiae, a mass of 14,900 ng has been
      attributed as the uptake limit of Cd for each disk. Determination of the Cd
      retained in the binding agent was readily carried out using a slurry of the
      agarose-yeast disk introduced directly into the inductively coupled plasma
      optical emission spectrometer. The performance characteristics of the DGT
      samplers, which were assembled with the proposed binding agent (25 mm disk
      containing 20% of S. cerevisiae and 1.5% of agarose) and a diffusive layer of
      cellulose (chromatographic paper 3MM Chr of 25 mm diameter), were evaluated by
      measuring the Cd(II) uptake at various pH values and ionic strengths. Very
      consistent results were found within the pH range 4.5-7.5 and at ionic strengths
      >=0.005 molL(-1). The precision of DGT measurements was characterized by relative
      standard deviations of <8%. No changes in the uptake of Cd(II) were observed in
      the samplers that were assembled with recently prepared disks or 35-day-old
      stored disks. The proposed material has been applied to the analyses of river and
      sea water samples. For determination of Cd(II), excellent agreement between the
      results obtained from devices assembled with the proposed material and those
      assembled with conventional material (Chelex-100 resin) were obtained, strongly
      validating the use of the agarose-yeast gel disk as a new binding agent for DGT.

PMID- 21094389
TI  - Comparative surface plasmon resonance and enzyme-linked immunosorbent assay
      characterisation of a monoclonal antibody with N-acyl homoserine lactones.
AB  - This study shows the detection of (N-acyl) homoserine lactones (AHLs or HSL) with
      monoclonal antibodies via a surface plasmon resonance (SPR)-based immunosensor in
      comparison to conventional microtiter plate-based enzyme-linked immunosorbent
      assay (ELISA). An HSL derivative, named HSL2 (Table 1), was attached to bovine
      serum albumin (BSA) and the conjugate (HSL2-BSA-r2) was either covalently
      immobilised on the SPR sensor chip surface via free amino groups or via
      adsorption on the ELISA polystyrene plate surface. With a newly developed rat
      monoclonal antibody (mAb HSL1/2 2C10), AHLs were detected sensitively in a
      competitive format with SPR and ELISA. Well comparable experiments between SPR
      and ELISA could be obtained in buffers. Moreover, the SPR sensor surface with the
      immobilised conjugate HSL2-BSA-r2 could be regenerated at least 340 times
      (regeneration cycles) without loss of activity. The measurement time per cycle
      was approximately 15 min. The competitive detection format for SPR and ELISA
      allowed the detection in the MUgL(-1) range.

PMID- 21094391
TI  - Optimization of ultrasound assisted-emulsification-dispersive liquid-liquid
      microextraction by experimental design methodologies for the determination of
      sulfur compounds in wines by gas chromatography-mass spectrometry.
AB  - A new method was developed for analyzing sulfur compounds in the aroma of white
      wines using ultrasound assisted-emulsification-dispersive liquid-liquid
      microextraction coupled with gas chromatography-mass spectrometry detection. In
      the present work, the analytical method for simultaneous determination of seven
      sulfur compounds (methylmercaptoacetate, methyl(methylthio)acetate, 2
      methylthioethanol, 3-methylthiopropanol, 3-methylthiohexanol, 4-methylthio-4
      methyl-2-pentanone and hexanethiol) is reported. Parameters that affect the
      efficiency of the methodology such as extracting and dispersing solvents, sample
      volume, ion strength, cavitation time and centrifugation time were investigated
      using a fractionated factorial 2(6-1) (R=V) screening design. Then, the factors
      presenting significant positive effects on the analytical response (extracting
      volume, ion strength, cavitation time and centrifugation time) were considered in
      a further central composite design to optimize the operational conditions for the
      ultrasound assisted-emulsification-dispersive liquid-liquid microextraction
      procedure. Additionally, multiple response simultaneous optimization by using the
      desirability function was used to find the optimum experimental conditions. The
      best results were obtained using pH sample 4.25, extractant volume 150MUL, ionic
      strength 8.75% NaCl, cavitation time 20s and centrifugation time 50s. The use of
      the optimized ultrasound assisted-emulsification-dispersive liquid-liquid
      microextraction technique allowed to obtain the best extraction results with the
      minimum interference from other substances from the matrix, and it allowed to
      quantify the analytes in white wine samples by calibration graphs. Recoveries
      ranging from 91.99% to 125.87% for all sulfur compounds proved the accuracy of
      the proposed method in white wine samples. Method detection limits were in the
      range of 0.36-1.67ngmL(-1) and limits of quantitation were between 0.63 and
      3.02ngmL(-1) for sulfur compounds in white wine samples. The proposed methodology
      was successfully applied for the determination concentrations of sulfur compounds
      in different commercial Chardonnay wine samples from Mendoza, Argentine.

PMID- 21094390
TI  - Identification of bioactive peptides in hypoallergenic infant milk formulas by
      capillary electrophoresis-mass spectrometry.
AB  - In this study, we use capillary electrophoresis-mass spectrometry (CE-MS) for the
      identification of bioactive peptides in hypoallergenic infant milk formulas (IF),
      which are complex bovine milk protein hydrolysates. A sample clean-up
      pretreatment with a citrate buffer containing dithiothreitol and urea followed by
      solid-phase extraction (SPE) with different reversed-phase commercial cartridges
      was investigated to achieve optimum detection sensitivity in CE-MS. SPE with C18,
      StrataX and Oasis HLB cartridges allowed detection of the largest number of low
      molecular mass components, but combination of C18 and StrataX results was enough
      to achieve an excellent coverage of the studied IF. The monoisotopic molecular
      mass values of the low molecular mass components obtained by capillary
      electrophoresis ion-trap mass spectrometry (CE-IT-MS) allowed the tentative
      identification of nine bioactive sequences. Only the identification of five of
      them could be confirmed when accurate mass measurements were performed by
      capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS), namely
      LKP, IPY, ALPM, PGPIHN and VAGTWY, which were reported to present angiotensin
      converting enzyme (ACE) inhibitory and antimicrobial activity (only VAGTWY).

PMID- 21094392
TI  - High temporal resolution monitoring of enzyme reaction and inhibition using
      optically gated vacancy capillary electrophoresis and immobilized enzyme.
AB  - A novel method for monitoring of enzyme reaction and inhibition with high
      temporal resolution was developed by using optically gated vacancy capillary
      electrophoresis (OGVCE) with laser-induced fluorescence (LIF) detection and
      immobilized enzyme. Trypsin cleavage reaction and inhibition were investigated by
      the presented OGVCE-LIF assay, using carboxyfluorescein (FAM) end-labeled
      Angiotensin as the substrate and commercially available immobilized trypsin. The
      substrate and the product were continuously loaded into the capillary by the
      electroosmotic flow while the immobilized enzyme remained in the sample vial.
      Substrate consumption and product formation were monitored simultaneously at 5s
      interval during the whole reaction time. The enzymatic reaction rates obtained
      from the substrate and the product were highly consistent. The enzyme activity
      and the Michaelis constants of trypsin cleavage reaction, as well as the
      inhibition constant (for reversible competitive inhibitor) and the inhibition
      fraction (for irreversible inhibitor), were obtained. It was showed that the
      reported OGVCE-LIF method can perform fast, accurate, sensitive and reproducible
      CE enzyme assay with high temporal resolution, thus has great potential in
      application of the enzyme-substrate systems with fast reaction rate and the
      fluorescent substrate and products.

PMID- 21094393
TI  - Clozapine imprinted polymers: synthesis, characterization and application for
      drug assay in human serum.
AB  - A variety of molecularly imprinted polymers (MIPs) against clozapine (CLZ) were
      synthesized and their recognition properties were compared with blank non
      imprinted polymers. Methacrylic acid (MAA) was used as a functional monomer and
      Chloroform or tetrahydrofuran (THF) were applied as polymerization solvents.
      Chloroform as the solvent and MAA/CLZ ratio of 5 was selected as optimized
      polymerization condition. In Scatchard analysis of MIP-CLZ interactions, two
      classes of binding sites were found in MIP-high affinity (KD=14.5MUM) and low
      affinity (KD=322.5MUM) binding sites. The polymer was evaluated as a selective
      sorbent in molecularly imprinted solid-phase extraction (MISPE) of CLZ from human
      serum. The MISPE procedure was developed and optimized with a recovery of 88
      102%. The intra- and inter-day precision values were less than 1.36% and 2.5%,
      respectively. The selectivity of MISPE for CLZ was studied in comparison with
      some drugs. These drugs could be present with CLZ, simultaneously in serum of
      patients. The data indicated that the imprinted polymer had a good selectivity
      and affinity for CLZ and could be used for selective extraction and analysis of
      CLZ in human serum.

PMID- 21094394
TI  - The quality of teacher-student interactions: associations with first graders'
      academic and behavioral outcomes.
AB  - The associations between the quality of teacher-student interactions and first
      grade academic and adaptive behavior outcomes were examined in a study of 106
      Portuguese students in 64 first grade classrooms. Students' vocabulary, print
      concepts, math, and adaptive skills were assessed both at the end of preschool
      and in first grade. Classrooms were observed in the spring of first grade. After
      taking into account family risk factors and preschool skills, the quality of
      teacher-student interactions, particularly in terms of classroom organization,
      was positively associated with students' first grade vocabulary and print
      concepts. In addition, classroom quality predicted number identification outcomes
      differently depending on student skills prior to school entry. Students with
      lower preschool math skills seemed to benefit from higher quality teacher-student
      interactions. These findings provide further support for the unique contribution
      of the quality of teacher-student interactions in first grade and suggest that it
      may be an important mechanism to improve academic skills.

PMID- 21094395
TI  - Relatedness with teachers and peers during early adolescence: an integrated
      variable-oriented and person-oriented approach.
AB  - The primary aims of the present longitudinal study were to examine (a) patterns
      of early transition relatedness with teachers and peers in 6th grade, (b) whether
      pre-transition behavior in 5th grade predicted early transition relatedness in
      6th grade, and (c) how unique indicators of early transition relatedness with
      teachers and peers and patterns of early transition relatedness were associated
      with school adjustment among 383 rural, lower- to middle-class, White youth.
      Results suggest that behavioral characteristics in elementary school may
      contribute to early transition patterns of relatedness with teachers and peers in
      middle school. Findings also indicate that having a pattern of poor relationships
      with the primary social partners in the school context is negatively associated
      with adjustment above and beyond the independent indicators of relatedness.
      Implications for school practice are discussed.

PMID- 21094396
TI  - Gender differences in the relative impact of physical and relational bullying on
      adolescent injury and weapon carrying.
AB  - Using structural equation modeling, concurrent associations were assessed among
      physical bullying, relational bullying, physical victimization, relational
      victimization, injury and weapon carrying using data from the population of 1300
      adolescent girls and 1362 adolescent boys in grades 7-12 in a Colorado school
      district. For both genders, being a relational bully was a significantly stronger
      predictor of weapon carrying than being a physical bully, and both bullying types
      were significant predictors of more weapon carrying. For both genders, being a
      victim of physical bullying, a victim of relational bullying, or being a
      relational bully significantly predicted more injury. In latent means
      comparisons, adolescent girls reported more relational victimization and
      adolescent boys reported more physical bullying and victimization, more weapon
      carrying, and more injury. The relative strength of relational bullying on weapon
      carrying, and the health-related consequences of bullying on interpersonal
      violence and injury support concerted efforts in schools to mitigate these
      behaviors. Attention to differences related to age and gender also is indicated
      in the design of bullying mitigation programs.

PMID- 21094397
TI  - Supportive school climate and student willingness to seek help for bullying and
      threats of violence.
AB  - This study investigated the relations between student perceptions of support and
      student willingness to seek help for bullying and threats of violence in a sample
      of 7318 ninth-grade students from 291 high schools who participated in the
      Virginia High School Safety Study. Hierarchical linear modeling indicated that
      students who perceived their teachers and other school staff to be supportive
      were more likely to endorse positive attitudes toward seeking help for bullying
      and threats of violence. In schools with more perceived support, there was less
      of a discrepancy in help-seeking attitudes between girls and boys. Findings
      suggest that efforts by school staff to provide a supportive climate are a
      potentially valuable strategy for engaging students in the prevention of bullying
      and threats of violence.

PMID- 21094399
TI  - Preface sports medicine imaging.

PMID- 21094398
TI  - The impact of parents, child care providers, teachers, and peers on early
      externalizing trajectories.
AB  - This study utilized growth mixture modeling to examine the impact of parents,
      child care providers, teachers, and peers on the prediction of distinct
      developmental patterns of classroom externalizing behavior in elementary school.
      Among 241 children, three groups were identified. 84.6% of children exhibited
      consistently low externalizing behavior. The externalizing behavior of the
      Chronic High group (5.8%) remained elevated throughout elementary school; it
      increased over time in the Low Increasing group (9.5%). Negative relationships
      with teachers and peers in the kindergarten classroom increased the odds of
      having chronically high externalizing behavior. Teacher-child conflict increased
      the likelihood of a developmental pattern of escalating externalizing behavior.
      Boys were overrepresented in the behaviorally risky groups, and no sex
      differences in trajectory types were found.

PMID- 21094400
TI  - Basketball injuries.
AB  - Basketball injuries are most prevalent in the lower extremity, especially at the
      ankle and knee. Most basketball injuries are orthopedic in nature and commonly
      include ligament sprains, musculotendinous strains, and overuse injuries
      including stress fractures. By virtue of its excellent contrast resolution and
      depiction of the soft tissues and trabecular bone, magnetic resonance imaging has
      become the principal modality for evaluating many basketball injuries. In this
      article, commonly encountered basketball injuries and their imaging appearances
      are described. The epidemiology of basketball injuries across various age groups
      and levels of competition and between genders are reviewed.

PMID- 21094401
TI  - Skiing and snowboarding injuries: a review with a focus on mechanism of injury.
AB  - Skiing and snowboarding are ever increasing in popularity, with participation
      across a wide patient demographic. This article focuses on common skiing and
      snowboarding injuries, with an emphasis on unique mechanisms of injury and
      discusses the contribution of equipment design to evolving patterns of injury.
      Knowledge of mechanisms of injury and injury patterns allows a targeted approach
      to the interpretation of imaging modalities in this patient population.

PMID- 21094402
TI  - Imaging of triathlon injuries.
AB  - Injuries in triathletes are common and are mostly overuse injuries. Rotator cuff
      tendinitis is the most common complaint from swimming, but the incidence of
      tendinopathy and rotator cuff tears on magnetic resonance imaging is comparable
      in triathletes without and with shoulder pain. Cycling injuries are mainly to the
      knee, including patellar tendinosis, iliotibial band syndrome, and patellofemoral
      stress syndrome, and to the Achilles tendon and the cervical and lumbar spine.
      Running is associated with most injuries in triathletes, during both training and
      racing, causing the athlete to discontinue the triathlon. In addition to knee
      injuries from running, triathletes may also develop foot and ankle, lower leg,
      and hip injuries similar to single-sport distance runners. Some injuries in
      triathletes may be mainly symptomatic during one of the three sports but are
      exacerbated by one or both of the other disciplines.

PMID- 21094403
TI  - Overhead throwing injuries of the shoulder and elbow.
AB  - Injuries to the shoulder and elbow are common in athletes involved in sporting
      activities that require overhead motion of the arm. An understanding of the
      forces involved in the throwing motion, the anatomic structures most at risk, and
      the magnetic resonance imaging appearances of the most common associated injuries
      can help to improve diagnostic accuracy when interpreting imaging studies in
      these patients.

PMID- 21094404
TI  - Hip injuries in athletes.
AB  - Hip injuries are common in athletes, and there is an extensive differential
      diagnosis of potential causes. This article reviews the anatomy of the hip, and
      discusses the imaging findings of hip pathology in athletes including skeletal,
      intraarticular, and extra-articular abnormalities. The role of radiography,
      computed tomography (CT), magnetic resonance (MR) imaging, MR arthrography, CT
      arthrography, and sonography in evaluating each condition is discussed.

PMID- 21094405
TI  - The spectrum of MR imaging in athletic pubalgia.
AB  - Many athletes struggle with groin pain for years without ever receiving a clear
      diagnosis or being offered an effective treatment plan. Confusion among treatment
      providers can also frequently lead to suboptimal surgeries for presumed hernias
      or nerve entrapment syndromes. Imaging, and in particular magnetic resonance (MR)
      imaging, should play a primary role in the workup, diagnosis, and treatment of
      athletic pubalgia. This review outlines standard of care, cutting-edge MR imaging
      techniques for athletic pubalgia, and reviews the spectrum of imaging findings
      that are encountered in this patient group.

PMID- 21094406
TI  - Imaging pediatric sports injuries: upper extremity.
AB  - With increasing youth participation in organized sports, more injuries in this
      age group are being treated by primary care and sports medicine physicians.
      Overuse injuries are much more common now than in past decades, with Little
      League shoulder, Little League elbow, and gymnast wrist being particular
      concerns. Rotator cuff tears and glenoid labral injuries, once thought to be rare
      in this age group, are also more common now. Osteochondritis dissecans of the
      elbow is relatively common and typically fares poorly without surgery. Wrist
      abnormalities that occur nowadays include triangular fibrocartilage tears.
      Tendonitis, which is now observed frequently in clinical practice in this age
      group, rarely requires imaging.

PMID- 21094407
TI  - Imaging pediatric sports injuries: lower extremity.
AB  - Injuries to pediatric athletes, which are becoming increasingly common, take the
      form of acute injuries and chronic overuse injuries. Acute injuries of the lower
      extremity include avulsions of the pelvic apophyses, muscle-tendon injuries,
      transient dislocation of the patella, ankle sprains, and acute tears of the
      anterior cruciate ligament and menisci. Magnetic resonance (MR) imaging of the
      latter 2 injuries should approach the accuracy of MR imaging of the adult knee.
      Chronic overuse injuries of the lower extremity in this age group include stress
      fractures, which are most common in the tibia; ankle impingement syndromes;
      osteochondritis dissecans of the knee and osteochondral lesions of the talus; and
      traction apophysitis, most commonly presenting as Osgood-Schlatter disease and
      Sinding-Larsen-Johannson disease, affecting the patellar tendon. Imaging findings
      of all these lesions are characteristic, and allow radiologists to assist their
      clinical colleagues in diagnosing and treating pediatric athletic injuries.

PMID- 21094408
TI  - Sports-related injury of the pediatric spine.
AB  - Acute spinal injuries are fortunately rare in pediatric sports but can be
      catastrophic. Imaging is integral to the diagnosis and care of spinal trauma.
      Plain radiographs and CT are critical for detecting vertebral fracture, and MR
      imaging is an essential adjunct for evaluating muscular, ligamentous, and spinal
      cord injury. Back pain is a common complaint among athletes of all ages. The
      growing spine has unique weaknesses that result in a higher rate of detectable
      radiologic abnormalities. Disk pathology is less common in children, and is often
      uniquely associated with fracture of the ring apophyses. Spondylolysis is far
      more prevalent in youth athletes than in their adult counterparts, requiring a
      different approach to imaging for assessment of adolescent back pain.

PMID- 21094409
TI  - The female athlete.
AB  - Over time, women have become more extensively involved in athletic programs. The
      female athlete presents a unique challenge to sports medicine in general.
      Although specific types of injuries are the same as in the male athlete, the
      female athlete is at higher risk for some of these injuries. Injuries may be
      sport specific, but gender-related injuries are also related to morphologic and
      physiologic differences between the male and female athlete. This article reviews
      some of the differences between the male and female athlete and focuses on a few
      prominent injuries or risks related specifically to the woman athlete.

PMID- 21094410
TI  - Vision Research special issue on "Perception and action".

PMID- 21094411
TI  - Global perinatal health: accelerating progress through innovations, interactions,
      and interconnections.

PMID- 21094412
TI  - 3.6 million neonatal deaths--what is progressing and what is not?
AB  - Each year 3.6 million infants are estimated to die in the first 4 weeks of life
      (neonatal period)--but the majority continue to die at home, uncounted. This
      article reviews progress for newborn health globally, with a focus on the
      countries in which most deaths occur--what data do we have to guide accelerated
      efforts? All regions are advancing, but the level of decrease in neonatal
      mortality differs by region, country, and within countries. Progress also differs
      by the main causes of neonatal death. Three major causes of neonatal deaths
      (infections, complications of preterm birth, and intrapartum-related neonatal
      deaths or "birth asphyxia") account for more than 80% of all neonatal deaths
      globally. The most rapid reductions have been made in reducing neonatal tetanus,
      and there has been apparent progress towards reducing neonatal infections.
      Limited, if any, reduction has been made in reducing global deaths from preterm
      birth and for intrapartum-related neonatal deaths. High-impact, feasible
      interventions to address these 3 causes are summarized in this article, along
      with estimates of potential for lives saved. A major gap is reaching mothers and
      babies at birth and in the early postnatal period. There are promising community
      based service delivery models that have been tested mainly in research studies in
      Asia that are now being adapted and evaluated at scale and also being tested
      through a network of African implementation research trials. To meet Millennium
      Development Goal 4, more can and must be done to address neonatal deaths. A
      critical step is improving the quantity, quality and use of data to select and
      implement the most effective interventions and strengthen existing programs,
      especially at district level.

PMID- 21094413
TI  - Stillbirths: epidemiology, evidence, and priorities for action.
AB  - The annual global burden of stillbirths amounts to an estimated 3.2 million%, 98%
      of which occur in low- and middle-income countries (LMICs). Of these, 1.02
      million (32%) are intrapartum, ie, taking place during labor. The most important
      causes of stillbirths in LMICs include obstructed or prolonged labor,
      hypertensive diseases of pregnancy, syphilis and gram-negative infections,
      malaria in endemic areas, and undernutrition. Interventions that target these
      causes can play an important role in reducing stillbirths. There is a clear
      benefit of emergency obstetrical care, particularly Cesarean delivery, on
      intrapartum rates in LMICs when Cesarean rates are less than 8% to 10%. Provision
      of a skilled birth attendant is another important intervention whereby labor
      complications can be prevented, identified, managed, and/or referred. Among
      interventions for infections, syphilis screening and treatment can prevent as
      many as 50% of all stillbirths in areas with high syphilis prevalence, reducing
      the risk of stillbirths among treated women to that of untreated women.
      Intermittent preventive treatment of malaria and insecticide-treated mosquito
      nets are also interventions with strong recommendation, especially in the first 2
      pregnancies. Balanced energy protein supplementation is an important nutritional
      intervention to prevent stillbirths in undernourished women, especially in LMICs.
      Creation of increased demand for health services within communities and
      increasing their uptake also can play a role in averting stillbirths. Other
      potential social and behavioral interventions include birth spacing, smoking
      cessation and indoor air pollution control, although the evidence for these is
      weak.

PMID- 21094414
TI  - Reducing intrapartum-related neonatal deaths in low- and middle-income countries
      what works?
AB  - Each year, 814,000 neonatal deaths and 1.02 million stillbirths result from
      intrapartum-related causes, such as intrauterine hypoxia. Almost all of these
      deaths are in low- and middle-income countries, where women frequently lack
      access to quality perinatal care and may delay care-seeking. Approximately 60
      million annual births occur outside of health facilities, and most of these
      childbirths are without a skilled birth attendant. Conditions that increase the
      risk of intrauterine hypoxia--such as pre-eclampsia/eclampsia, obstructed labor,
      and low birth weight--are often more prevalent in low resource settings.
      Intrapartum-related neonatal deaths can be averted by a range of interventions
      that prevent intrapartum complications (eg, prevention and management of pre
      eclampsia), detect and manage intrapartum problems (eg, monitoring progress of
      labor with access to emergency obstetrical care), and identify and assist the
      nonbreathing newborn (eg, stimulation and bag-mask ventilation). Simple,
      affordable, and effective approaches are available for low-resource settings,
      including community-based strategies to increase skilled birth attendance,
      partograph use by frontline health workers linked to emergency obstetrical care
      services, task shifting to increase access to Cesarean delivery, and simplified
      neonatal resuscitation training (Helping Babies Breathe(SM)). Coverage of
      effective interventions is low, however, and many opportunities are missed to
      provide quality care within existing health systems. In sub-Saharan Africa,
      recent health services assessments found only 15% of hospitals equipped to
      provide basic neonatal resuscitation. In the short term, intrapartum-related
      neonatal deaths can be substantially reduced by improving the quality of services
      for all childbirths that occur in health facilities, identifying and addressing
      the missed opportunities to provide effective interventions to those who seek
      facility-based care. For example, providing neonatal resuscitation for 90% of
      deliveries currently taking place in health facilities would save more than
      93,000 newborn lives each year. Longer-term strategies must address the gaps in
      coverage of institutional delivery, skilled birth attendance, and quality by
      strengthening health systems, increasing demand for care, and improving community
      based services. Both short- and long-term strategies to reduce intrapartum
      related mortality should focus on reducing inequities in coverage and quality of
      obstetrical and perinatal care.

PMID- 21094415
TI  - Preventing preterm birth and neonatal mortality: exploring the epidemiology,
      causes, and interventions.
AB  - Globally, each year, an estimated 13 million infants are born before 37 completed
      weeks of gestation. Complications from these preterm births are the leading cause
      of neonatal mortality. Preterm birth is directly responsible for an estimated one
      million neonatal deaths annually and is also an important contributor to child
      and adult morbidities. Low- and middle-income countries are disproportionately
      affected by preterm birth and carry a greater burden of disease attributed to
      preterm birth. Causes of preterm birth are multifactorial, vary by gestational
      age, and likely vary by geographic and ethnic contexts. Although many
      interventions have been evaluated, few have moderate-to high-quality evidence for
      decreasing preterm birth: smoking cessation and progesterone treatment in women
      with a high risk of preterm birth in low- and middle-income countries and
      cervical cerclage for those in high-income countries. Antepartum and postnatal
      interventions (eg, antepartum maternal steroid administration, or kangaroo mother
      care) to improve preterm neonatal survival after birth have been demonstrated to
      be effective but have not been widely implemented. Further research efforts are
      urgently needed to better understand context-specific pathways leading to preterm
      birth; to develop appropriate, efficacious prevention strategies and
      interventions to improve survival of neonates born prematurely; and to scale-up
      known efficacious interventions to improve the health of the preterm neonate.

PMID- 21094416
TI  - Neonatal infections in the developing world.
AB  - An estimated one million newborns die from infections in developing countries.
      Despite the huge burden, high-quality data from community-based epidemiologic
      studies on etiology, risk factors, and appropriate management are lacking from
      areas in which newborns experience the greatest mortality. Several planned and
      ongoing studies in South Asia and Africa promise to address the knowledge gaps.
      However, simple and low-cost interventions, such as community-based neonatal care
      packages supporting clean birth practices, early detection of illness through use
      of clinical algorithms, and home-based antibiotic therapy in areas in which
      hospitalization is not feasible are already available and have the potential to
      bring about a drastic reduction in global neonatal mortality due to infections if
      they are scaled up to national level. Concerted collaborative action by national
      governments, health professionals, civil society organizations, and international
      health agencies is required to reduce neonatal mortality due to infections.

PMID- 21094417
TI  - Neonatal hypothermia in low-resource settings.
AB  - Hypothermia among newborns is considered an important contributor to neonatal
      morbidity and mortality in low-resource settings. However, in these settings only
      limited progress has been made towards understanding the risk of mortality after
      hypothermia, describing how this relationship is dependent on both the degree or
      severity of exposure and the gestational age and weight status of the baby, and
      implementing interventions to mitigate both exposure and the associated risk of
      poor outcomes. Given the centrality of averting neonatal mortality to achieving
      global milestones towards reductions in child mortality by 2015, recent years
      have seen substantial resources and efforts implemented to improve understanding
      of global epidemiology of neonatal health. In this article, a summary of the
      burden, consequences, and risk factors of neonatal hypothermia in low-resources
      settings is presented, with a particular focus on community-based data. Context
      appropriate interventions for reducing hypothermia exposure and the role of these
      interventions in reducing global neonatal mortality burden are explored.

PMID- 21094418
TI  - Linkages among reproductive health, maternal health, and perinatal outcomes.
AB  - Some interventions in women before and during pregnancy may reduce perinatal and
      neonatal deaths, and recent research has established linkages of reproductive
      health with maternal, perinatal, and early neonatal health outcomes. In this
      review, we attempted to analyze the impact of biological, clinical, and
      epidemiologic aspects of reproductive and maternal health interventions on
      perinatal and neonatal outcomes through an elucidation of a biological framework
      for linking reproductive, maternal and newborn health (RHMNH); care strategies
      and interventions for improved perinatal and neonatal health outcomes; public
      health implications of these linkages and implementation strategies; and evidence
      gaps for scaling up such strategies. Approximately 1000 studies (up to June 15,
      2010) were reviewed that have addressed an impact of reproductive and maternal
      health interventions on perinatal and neonatal outcomes. These include systematic
      reviews, meta-analyses, and stand-alone experimental and observational studies.
      Evidences were also drawn from recent work undertaken by the Child Health
      Epidemiology Reference Group (CHERG), the interconnections between maternal and
      newborn health reviews identified by the Global Alliance for Prevention of
      Prematurity and Stillbirth (GAPPS), as well as relevant work by the Partnership
      for Maternal, Newborn and Child Health. Our review amply demonstrates that
      opportunities for assessing outcomes for both mothers and newborns have been
      poorly realized and documented. Most of the interventions reviewed will require
      more greater-quality evidence before solid programmatic recommendations can be
      made. However, on the basis of our review, birth spacing, prevention of indoor
      air pollution, prevention of intimate partner violence before and during
      pregnancy, antenatal care during pregnancy, Doppler ultrasound monitoring during
      pregnancy, insecticide-treated mosquito nets, birth and newborn care preparedness
      via community-based intervention packages, emergency obstetrical care, elective
      induction for postterm delivery, Cesarean delivery for breech presentation, and
      prophylactic corticosteroids in preterm labor reduce perinatal mortality; and
      early initiation of breastfeeding and birth and newborn care preparedness through
      community-based intervention packages reduce neonatal mortality. This review
      demonstrates that RHMNH are inextricably linked, and that, therefore, health
      policies and programs should link them together. Such potential integration of
      strategies would not only help improve outcomes for millions of mothers and
      newborns but would also save scant resources. This would also allow for greater
      efficiency in training, monitoring, and supervision of health care workers and
      would also help families and communities to access and use services easily.

PMID- 21094419
TI  - Behavior change for newborn survival in resource-poor community settings:
      bridging the gap between evidence and impact.
AB  - Despite an established evidence base of simple, affordable, and low-cost
      interventions to avert neonatal deaths, global progress in reducing neonatal
      mortality has stagnated in recent years. Under-recognition of the critical role
      played by behavior change in ensuring adoption and dissemination of innovations
      is a major reason for this gap between evidence and impact. A general lack of
      understanding of the mechanisms underlying behavior change at a population level
      coupled with an under-appreciation of the sociocultural context of newborn care
      behaviors has underscored ill-informed approaches towards behavior change that
      have met with limited success. This article draws upon available evidence from
      prevention-oriented, community-based newborn survival trials to derive insights
      into the role of behavior change in neonatal mortality reduction. We propose a
      simple model, the intervention-causation pathway, to explain the pathway through
      which behavior change interventions may lead to reductions in mortality. Further,
      we explore the unique nature of newborn care behaviors and their underlying
      sociocultural context, along with state-of-the-art advances in social,
      behavioral, and management sciences. These principles form the basis of the
      behavior change management framework that has successfully guided intervention
      design and implementation, leading to high impact on neonatal mortality
      reduction, in Uttar Pradesh, India. We describe how the behavior change
      management framework can be applied to inform the design of theoretically and
      empirically sound behavior change interventions with greater precision,
      predictability and pace towards reduction in neonatal mortality. We finally touch
      upon key overarching principles that should guide intervention execution for
      maximal impact.

PMID- 21094420
TI  - Community-based intervention packages for improving perinatal health in
      developing countries: a review of the evidence.
AB  - The Lancet Neonatal Survival Series categorized neonatal health interventions
      into 3 service delivery modes: "Outreach," "Family-Community Care," and "Facility
      based Clinical Care." Family-Community Care services generally have a greater
      potential impact on neonatal health than Outreach services, with similar costs.
      Combining interventions from all 3 service delivery modes is ideal for
      achievement of high impact. However, access to clinical care is limited in
      resource-poor settings with weak health systems. The current trend for those
      settings is to combine neonatal interventions into community-based intervention
      packages (CBIPs), which can be integrated into the local health care system. In
      this article, we searched several large databases to identify all published,
      large-scale, controlled studies that were implemented in a rural setting,
      included a control group, and reported neonatal and/or perinatal mortality as
      outcomes. We identified only 9 large-scale studies that fit these criteria.
      Several conclusions can be reached. (1) Family-Community Care interventions can
      have a substantial effect on neonatal and perinatal mortality. (2) Several
      important common strategies were used across the studies, including community
      mobilization, health education, behavior change communication sessions, care
      seeking modalities, and home visits during pregnancy and after birth. However,
      implementation of these interventions varied widely across the studies. (3) There
      is a need for additional, large-scale studies to test evidence-based CBIPs in
      developing countries, particularly in Africa, where no large-scale studies were
      identified. (4) We need to establish consistent, clearly defined terminology and
      protocols for designing trials and reporting outcomes so that we are able to
      compare results across different settings. (5) There is an urgent need to invest
      in research and program development focusing on neonatal health in urban areas.
      (6) It is crucial to integrate CBIPs in rural and urban settings into the already
      existing health care system to facilitate sustainability of the program and for
      scaling up. It is also important to evaluate the packages and to demonstrate the
      health impact of large-scale implementation. (7) Finally, there is a need for
      improving the continuum of care between home and facility-based care.

PMID- 21094421
TI  - Why is continuum of care from home to health facilities essential to improve
      perinatal survival?
AB  - The period around the time of delivery is extremely hazardous for infants in
      developing countries. After the first week the risk drops sharply, and survival
      improves markedly. To reduce perinatal mortality, a continuum of care between the
      home and the various facilities is essential during pregnancy, childbirth and the
      newborn period. This paper reviews strategies to promote the establishment of
      this continuum: providing health care within or close to home by frontline
      workers and increasing the use of services in health facilities through community
      mobilization and financing strategies. As perinatal care and care for seriously
      sick children face common challenges and lessons could be learned from successful
      strategies for management of other illnesses, this paper also reviews
      intervention models involving community health workers (CHWs) to improve case
      management of sick children at the household and community levels. Available
      evidence suggests that the community strategy with the greatest impact on
      neonatal mortality is home visits by CHWs combined with community mobilization.
      The same strategy appears to be effective in increasing health facility
      utilization. An equally effective strategy for increasing health facility
      utilization seems to be financing health care to remove financial access
      barriers, particularly using conditional cash transfers or vouchers. Although the
      availability of information on the effect of community interventions to improve
      newborn health has increased in the recent past, significant gaps remain.
      Information on the effectiveness of strategies in different settings,
      particularly in sub-Saharan Africa, cost-effectiveness and sustainability are
      particularly needed and should be gathered in future studies.

PMID- 21094422
TI  - Replicon particle vaccine protects swine against influenza.
AB  - An alphavirus derived replicon particle (RP) vaccine expressing the cluster IV
      H3N2 swine influenza virus (SIV) hemagglutinin (HA) gene induced protective
      immunity against homologous influenza virus challenge. However, pigs with
      maternal antibody had no protective immunity against challenge after vaccination
      with RP vaccines expressing HA gene alone or in combination with nucleoprotein
      gene.

PMID- 21094423
TI  - Genetic structure of Streptococcus pneumoniae isolated from children in a
      tertiary care university hospital, in Korea, 1995 to 2005.
AB  - We investigated the genetic structure of Streptococcus pneumoniae isolated from
      Korean children prior to the use of heptavalent pneumococcal conjugate vaccine
      (PCV7). A total of 278 pneumococcal isolates were obtained from invasive (n = 77)
      and noninvasive (n = 201) specimens from children < 5 years of age that visited
      the Seoul National University Children's Hospital between 1995 and 2005; these
      samples were serotyped. Two hundred seventy-eight isolates were characterized by
      multilocus sequence typing, antibiotic susceptibility pattern testing with the E
      test. The common serotypes were 19F (22.7%), 23F (19.1%), 19A (14.4%), 6B
      (11.2%), 6A (8.3%), 14 (5.4%), and 9V (4.3%); these 7 serotypes accounted for
      85.3% of the 278 isolates. The isolates belonged to 23 serotypes and 81 sequence
      types (STs) (including 48 newly discovered STs). The eBURST analysis showed 7
      clonal complexes (CCs). CC271 was the main CC of serogroup 19; CC81 and CC3115,
      serotype 6A; CC81 and CC880, serotype 23F; CC90, serotype 6B; CC166, serotype 9V;
      and CC554, serotype 14. Nonsusceptibility rates to penicillin and erythromycin
      among the invasive isolates were 9.1% and 94.8%, respectively. The resultant
      database may be useful for postvaccine surveillance.

PMID- 21094424
TI  - Identification of staphylococci by Phoenix: validation of a new protocol and
      comparison with Vitek 2.
AB  - Because of their frequent isolation in the routine laboratory and their
      increasing clinical significance, fast and accurate species identification of
      staphylococci may be required; this can only be achieved by automated systems. A
      total of 147 clinical isolates (52 Staphylococcus aureus, 50 Staphylococcus
      epidermidis, and 45 other coagulase-negative staphylococci [CoNS]) were first
      identified by molecular methodology and then comparatively tested by Vitek 2 (new
      colorimetric identification card) and Phoenix using the novel 0.25 McFarland and
      the standard 0.50 McFarland inoculum protocols. All S. aureus isolates were
      accurately identified. Vitek 2 identified correctly all S. epidermidis and 93.3%
      of the other CoNS, whereas the respective rates were 86% and 82.2% for Phoenix's
      standard and 92% and 82.2% for the novel protocol. It appears that both systems
      provide excellent identification of S. aureus, but Vitek 2 recognizes CoNS
      species more accurately than Phoenix. The 0.25 McFarland protocol does not
      improve system performance.

PMID- 21094425
TI  - Evaluation of synthetic peptides of WbSXP-1 for the diagnosis of human lymphatic
      filariasis.
AB  - Parasitic nematodes infect nearly half of the world's human population, resulting
      in significant morbidity and mortality. Though filariasis is not fatal, it is the
      second leading cause of permanent and long-term disability worldwide. Filariasis
      has a spectrum of disease manifestation and infectivity found among the infected
      individuals and also goes unnoticed for years. Furthermore, there are ample
      reports emerging on the genetic variation among the parasites population. Hence,
      it is necessary to develop diagnostics for early detection of the disease.
      Synthetic peptides that mimic the immunogenic regions and a conserved region
      similar to that of recombinant antigen will be more useful in developing
      diagnostics, vaccines, or therapeutics. WbSXP-1 was earlier proven as a good
      diagnostic antigen; B-cell epitopic analysis showed 4 potent immunodominant
      regions spanning the whole antigen. These synthetic peptides (N, N1, N2, and N3)
      were produced and used as a diagnostic candidate to detect anti-SXP antibody and
      conversely to detect the infected individuals. The monomeric peptides showed good
      reactivity against microfilareamic (MF) sera. Among them, the peptides N, N1, and
      N2 were found to be more reactive. Furthermore, multiple chimeric peptides in
      linear combinations of 2 peptides were tested for its efficacy to detect anti-SXP
      antibody in infected MF sera. The peptides N:N1 and N1:N2 were synthesized and
      tested against human clinical sera. This chimeric peptides constructed based on
      WbSXP-1 were found to be reactive, specifically with MF sera by ELISA. These
      peptide-based diagnostic method can serve as a standard better tool without cross
      reactivity in lymphatic filariasis elimination program.

PMID- 21094426
TI  - Alternative visual displays of metaanalysis of malaria treatment trials to
      facilitate translation of research into policy.
AB  - Typically, metaanalyses show relative effects and heterogeneity, but not absolute
      effects-an essential element in policy decision. Data obtained through a
      systematic review of antimalarial treatment trials and virtual trials were used
      to generate a display that shows and quantifies absolute and relative effects as
      well as heterogeneity for comparative trials results. A plot of failure rates
      (with 95% confidence intervals) of the test drug on the y axis against the risk
      difference (RD) versus the comparator drug on the x axis is proposed; the area is
      divided into 4 quadrants by a vertical line (no RD) and a horizontal line
      (maximum tolerated failures, e.g., 10% for antimalarials). This allows
      identifying where a drug can be used (meeting efficacy requirements) and
      quantifying differences (versus another treatment option). The area of the
      polygon connecting the study points expresses heterogeneity. This graphic display
      is simple to prepare and interpret and combines in 1 graph both measures of
      absolute treatment effect and difference, as well as heterogeneity. It may
      complement current methods and provide useful information in policy decision
      making.

PMID- 21094427
TI  - Two successfully treated cases of Staphylococcus lugdunensis endocarditis.
AB  - Prosthetic valve and pacemaker lead endocarditis by Staphylococcus lugdunensis
      remain very rare, while the former is associated with an ominous prognosis. Two
      cases involving a prosthetic aortic valve and a pacemaker lead, respectively, are
      reported. Despite disease severity and delayed diagnosis, patients recovered
      fully with combined antimicrobial and surgical treatment.

PMID- 21094428
TI  - Stability of linezolid activity in an era of mobile oxazolidinone resistance
      determinants: results from the 2009 Zyvox(r) Annual Appraisal of Potency and
      Spectrum program.
AB  - Linezolid is the only oxazolidinone agent approved for clinical use and has been
      administered to millions of patients over nearly a decade, becoming an important
      therapeutic alternative for infections caused by multidrug-resistant (MDR) Gram
      positive pathogens. Resistance is due to mutations in 23S rRNA and the ribosomal
      proteins L3 and L4 and, more recently, the mobile cfr gene (causes resistance to
      several antimicrobial classes). Using reference broth microdilution methods in a
      central reference laboratory design, MIC values were obtained during the 2009
      Zyvox(r) Annual Appraisal of Potency and Spectrum program (5754 sampled strains
      from 22 countries), and the following MIC(90) values were obtained for the
      leading pathogen or species groups: Staphylococcus aureus (2 MUg/mL), coagulase
      negative staphylococci (CoNS; 1 MUg/mL), Enterococcus spp. (2 MUg/mL), and 3
      groups of streptococci (1 MUg/mL) including Streptococcus pneumoniae. Linezolid
      resistant strains (8 or 0.14% overall) that were not Staphylococcus aureus were
      observed in 5 nations and included CoNS (0.48%) having the mobile cfr gene. The
      results of this study demonstrate that linezolid continues to be effective in
      vitro against MDR pathogens, and the resistance rates appear stable.

PMID- 21094429
TI  - Stage-matched minimal interventions to enhance physical activity in Chinese
      adolescents.
AB  - PURPOSE: Interventions to improve physical activity (PA) might be successful when
      treatments are matched to the requirements of the recipients, in particular to
      their stage of change. This intervention study examines PA in Chinese high school
      students whose stage of change at the beginning of the study was identified.
      METHODS: Two minimal interventions (1 hour) were provided: resource communication
      and strategic planning. We assumed that preintenders would benefit in terms of PA
      frequency mainly from resource communication, and intenders would benefit from
      planning. Adolescents were assigned to an experimental and a control group.
      Moreover, they were divided according to stage (preintender, intender, actor). In
      the experimental group, each stage group received interventions. The data were
      analyzed with repeated measures analyses of variance (N = 534). Stage groups and
      treatment (resource communication, planning, and controls) were chosen as between
      subjects factors. PA frequency was the dependent variable measured at two points
      in time 4 weeks apart (pre-post measures). RESULTS: Preintenders in the resource
      communication condition improved their activity levels, whereas intenders
      increased their PA not only in the planning but also in resource communication
      conditions. Actors maintained their activity independently of the treatment they
      received, which was in line with the hypotheses. CONCLUSIONS: Matching PA
      interventions for adolescents to at least two stages of change might be a
      promising approach. Those who are not motivated to exercise benefit from resource
      based messages, whereas those who have behavioral intentions benefit from
      planning.

PMID- 21094430
TI  - Transition care for adolescents and families with chronic illnesses.
AB  - OBJECTIVES: To explore the attitudes of adolescents and parents toward transition
      care and to identify factors and barriers associated with transition decision.
      METHODS: The study was conducted at a pediatric out-patient clinic using a self
      administered questionnaire to evaluate the perspective of adolescent chronic
      patients on transition care for common chronic diseases. Despite its importance
      as emphasized in medical literature, transition care for adolescent patients with
      chronic illnesses is under-developed in Hong Kong. RESULTS: A total of 137
      adolescents aged 16-19 years, and 67 parents completed the survey; 85.3% of
      adolescents and 82.5% of parents were willing to transfer to adult care.
      "Adolescent's perception of his/her own responsibility towards chronic illness"
      was positively associated with willingness to transfer to adult care (OR = 3.84;
      95% CI, 1.41-10.45; p = .008), whereas "Detailed explanation by doctors"
      encouraged transition decision for adolescents (OR = 12.20; 95% CI, 1.22-122.33;
      p = .033). "Do not want to change" was the only significant barrier for
      transition for both adolescents (OR = .08; 95% CI, .01-.50; p = .007) and parents
      (OR = .07; 95% CI, .02-.36; p = .001). However, less than 10% of subjects had
      ever received any transition information from doctors or other healthcare
      workers. CONCLUSIONS: This is the first study in Asia region evaluating attitudes
      of adolescents and parents on transition care. The majority of adolescents and
      parents accept transition care from pediatrics to adult service, but only a small
      proportion has ever received transition information from doctors. Our findings
      should be useful to healthcare providers in planning transition care programmes
      for adolescent patients with chronic illnesses.

PMID- 21094431
TI  - Early exposure to parents' relationship instability: implications for sexual
      behavior and depression in adolescence.
AB  - PURPOSE: Examine the effects of the timing of parents' relationship instability
      on adolescent sexual and mental health. METHODS: We assessed whether the timing
      of parents' relationship instability predicted adolescents' history of sexual
      partnerships (SP) and major depressive episodes. Multivariate logistic regression
      analyses controlled for potential mediators related to parenting and the family,
      including parent knowledge of activities, parent-child relationship quality,
      number of parents' post-separation relationship transitions, and number of
      available caregivers. Participants were assessed annually from age 5 through
      young adulthood as part of a multisite community sample (N = 585). RESULTS:
      Participants who experienced parents' relationship instability before age 5 were
      more likely to report SP at age 16 (odds ratio [OR](adj) = 1.58) or an episode of
      major depression during adolescence (OR(adj) = 2.61). Greater parent knowledge at
      age 12 decreased the odds of SP at age 16, but none of the hypothesized parenting
      and family variables statistically mediated the association between early
      instability and SP or major depressive episode. CONCLUSIONS: These results
      suggest that experiencing parents' relationship instability in early childhood is
      associated with sexual behavior and major depression in adolescence, but these
      associations are not explained by the parenting and family variables included in
      our analyses. Limitations of the current study and implications for future
      research are discussed.

PMID- 21094432
TI  - Pilot multimethod trial of a school-ethos intervention to reduce substance use:
      building hypotheses about upstream pathways to prevention.
AB  - PURPOSE: Interventions to improve school ethos can reduce substance use but
      "upstream" causal pathways relating to implementation and school-level changes
      are uncertain. We use qualitative and quantitative data from a pilot trial to
      build hypotheses regarding these. METHODS: The Healthy School Ethos intervention
      involved two schools being provided with facilitation, training, and funding to
      plan and implement actions (some mandatory and some locally determined) to
      improve school ethos over one year. The evaluation involved a pilot-trial with
      two intervention and two comparison schools; semi-structured interviews with
      facilitators, staff, and students; and baseline and follow-up surveys with
      students aged 11 to 12 years. RESULTS: Student accounts linked participation in
      planning or delivering intervention activities with improved self-regard and
      relationships with staff and other students. Some activities such as re-writing
      school rules involved broad participation. Students in receipt of actions such as
      peer-mediation or motivational sessions reported benefits such as improved safety
      and relationships. Some student accounts linked improved self-regard and
      relationships with increased engagement and aspirations, and reduced substance
      use. At 9-month follow-up, students in intervention schools reported less hurting
      and teasing of others and feeling unsafe at school. Other outcomes suggested
      intervention benefits but were not significant. CONCLUSIONS: School-ethos
      interventions may reduce substance use through upstream pathways involving the
      aforementioned factors. Future phase-III trials should quantitatively model the
      extent to which these mediate intervention effects.

PMID- 21094433
TI  - A trajectory analysis of alcohol and marijuana use among Latino adolescents in
      San Francisco, California.
AB  - PURPOSE: We examined alcohol and marijuana use trajectories among Latino
      adolescents in the San Francisco Bay Area. METHODS: A total of 410 Latino
      adolescents aged 14-19 years were recruited from community venues from years 2001
      to 2004 and followed up for 2 years. In separate models, we identified groups
      with similar temporal patterns of alcohol and marijuana use using semi-parametric
      latent group trajectory modeling. Multivariable multinomial logistic regression
      was used to identify factors associated with the probability of trajectory group
      membership. RESULTS: The use of alcohol (76%) and marijuana (55%) in the previous
      6 months was common. Three alcohol-use trajectories were identified: low users
      (18%), moderate users (37%), and frequent users (45%). Low alcohol users (vs.
      moderate users) were found to be younger in age, preferred Spanish language, and
      had more parental monitoring. Frequent users were more likely to be male,
      sexually active, gang exposed, and have less parental monitoring than moderate
      users. Similarly, three marijuana-use trajectories were identified: low users
      (36%), moderate users (35%), and frequent users (28%), with similar correlates of
      group membership. CONCLUSIONS: Urban Latino adolescents' substance use is shaped
      by complex cultural and environmental influences. Patterns of substance use
      emerge by early adolescence highlighting the need for timely intervention.

PMID- 21094434
TI  - The effect of early maltreatment, victimization, and partner violence on HIV risk
      behavior among homeless young adults.
AB  - PURPOSE: The purpose of our study was to examine the relationship between child
      maltreatment, physical and sexual victimization, and partner violence
      victimization with human immunodeficiency virus (HIV) risk behaviors among a
      sample of homeless young adults from the midwestern United States. METHODS: Data
      are from the Homeless Young Adult Project. A total of 199 young adults aged 19-26
      years were interviewed over 14 months using a systematic sampling strategy. The
      final sample included 172 young adults who were homeless or had a history of
      running away and being homeless. RESULTS: Results from the path analysis revealed
      that sexual abuse is directly linked with street sexual victimization which was
      positively associated with a greater number of HIV risk behaviors. Experiencing
      more types of physical abuse and neglect were positively correlated with partner
      violence victimization, which was, in turn, associated with more HIV risk
      behaviors. Those who suffered from more types of neglect also experienced more
      forms of sexual and physical victimization. CONCLUSIONS: These findings have
      implications for service providers. Clinicians who serve homeless youth should
      recognize the potential effect that experiencing a variety of forms of
      victimization may have on health risk behaviors.

PMID- 21094435
TI  - Effects of self-esteem and academic performance on adolescent decision-making: an
      examination of early sexual intercourse and illegal substance use.
AB  - PURPOSE: To determine whether higher self-esteem and higher academic performance
      among youth reduce the likelihood of early sexual intercourse and illegal
      substance use. METHODS: Using data from waves I-III of the National Longitudinal
      Study of Adolescent Health, this study used multivariate logistic regression,
      stratified by gender and controlling for known covariates, to examine
      relationships between self-esteem and academic performance and youth decision
      making, specifically self-reported initiation of sexual intercourse and use of
      illegal substances. Self-esteem was constructed as an ascending scale of 10
      Likert-scaled survey items. Academic performance was assessed using the most
      recent grades from English, Math, Science, and History. RESULTS: Among virginal
      adolescents, higher self-esteem at baseline had no effect on sexual debut 1 year
      later. However, higher self-esteem at baseline among females corresponded with a
      significantly lower likelihood of illegal substance use 1 year later (OR, .96; p
      = .003). In terms of academic performance at baseline, girls averaging "A" grades
      as compared with girls averaging "C" grades or lower were significantly less
      likely to initiate sexual intercourse 1 year later (OR, .52; p = .004).
      Additionally among girls, being an "A" student or a "B" student was associated
      with lower odds of illegal substance use, compared with students who averaged "C"
      grades or lower (p < .01). Among young boys, self-esteem and academic performance
      were not significantly predictive of illegal substance use. CONCLUSIONS: This
      study suggests that bolstering self-esteem and improving academic performance
      among young girls may have specific benefits in sexual decision-making and
      substance-related risk-taking.

PMID- 21094436
TI  - Bone mineral content and density in obese, overweight, and normal-weighted
      sedentary adolescent girls.
AB  - PURPOSE: The aim of this study was to compare the whole body (WB) bone mineral
      content (BMC) and bone mineral density (BMD) in obese, overweight, and normal
      weighted adolescent sedentary girls. METHODS: This study included 17 obese, 27
      overweight, and 21 normal-weighted adolescent (aged, 12-20) sedentary (practicing
      less than 2 hours of physical activity/week) girls. The three groups (obese,
      overweight, and normal) were matched for age and maturation index (years since
      menarche). BMC, bone mineral area (BMA), BMD, and body composition were assessed
      by dual-energy X-ray asborptiometry. Bone mineral apparent density (BMAD) was
      calculated for the WB. RESULTS: Obese girls had higher BMC values than overweight
      and normal-weighted girls (p < .05 and p < .001, respectively). Overweight girls
      had higher BMC values than normal-weighted girls (p < .05). BMD values were not
      different among the three groups. However, obese and overweight girls had lower
      BMAD and higher BMC/height values in comparison with normal-weighted girls (p <
      .05). Finally, after adjustment for lean mass, BMC, BMA, BMD, and BMAD were not
      different among the three groups. CONCLUSION: In this population, overweight and
      obesity are associated with higher BMC, BMC/height, and lower BMAD of the WB.
      This study suggests that BMD, BMC, BMA, and BMAD of the WB are not significantly
      different among the three groups (obese, overweight, and normal) after adjustment
      for lean mass. Therefore, our results suggest that the skeleton of the overweight
      and the obese girls adapts to the increased lean mass.

PMID- 21094437
TI  - Factors associated with initiation and completion of human papillomavirus vaccine
      series among young women enrolled in Medicaid.
AB  - PURPOSE: To determine age- and race-specific uptake rates of human papillomavirus
      (HPV) vaccine among females aged 9-20 years who participated in the Florida
      Medicaid during the first 2 years after approval by the Food and Drug
      Administration, and to identify factors associated with HPV vaccine initiation
      and series completion. METHODS: Medicaid administrative data were used to
      identify claims for HPV vaccination together with individual, provider, and
      practice characteristics linked to each vaccination. RESULTS: As of June 2008,
      9.4% of females aged 11-18 years had ever received an HPV vaccination, and 1.8%
      had completed the three-vaccine series. In multivariate analysis, receipt of an
      HPV vaccination was found to be associated with age and race/ethnicity. In
      comparison with their white counterparts, black females were approximately half
      as likely to complete the three-vaccine series after initiation. CONCLUSIONS: The
      data obtained suggest relatively slow initial uptake and completion of the HPV
      vaccine series in this population who are at an increased risk for cervical
      cancer, with racial disparities in vaccine uptake and vaccine series completion.

PMID- 21094438
TI  - Associations between multiple pregnancies and health risk behaviors among U.S.
      adolescents.
AB  - PURPOSE: This study examined the associations between health risk behaviors
      (i.e., substance use behaviors, physical violence, or carried a weapon) and
      multiple adolescent pregnancies (i.e., experiencing or causing more than one
      pregnancy). METHODS: We analyzed 1999-2003 data (3 years: 1999, 2001, and 2003)
      from the National Youth Risk Behavior Survey, a nationally representative survey
      of high school students (N = 14,211 participants). Multinomial logistic
      regression was used to compare one and multiple pregnancies versus no
      pregnancies. Logistic regression was used to compare multiple pregnancies versus
      one pregnancy. RESULTS: A dose-response relationship was observed between
      multiple adolescent pregnancies and health risk behaviors; the more risk
      behaviors endorsed, the greater likelihood of experiencing or causing multiple
      adolescent pregnancies. Participants who engaged in a "high" degree of risk
      behaviors were significantly more likely to have experienced or caused multiple
      adolescent pregnancies than no pregnancies (or only one pregnancy) versus youth
      who endorsed no risk behaviors. Earlier sexual debut and more lifetime sexual
      partners were also associated with increased risk of endorsing multiple
      adolescent pregnancies. CONCLUSIONS: The health risk behaviors examined in our
      study can provide warning signs to influential persons who can potentially
      deliver important prevention messages to at-risk adolescents.

PMID- 21094440
TI  - The perception of adolescent medicine among health care professionals in Saudi
      Arabia.
AB  - The purpose of this study was to survey a group of Health Care Professionals
      (HCP) to assess their perception on adolescent health care and the need for
      dedicated adolescent health care facilities in the country. Cross-sectional,
      close-ended survey designed and administered to assess several categorical
      variables, was conducted on 500 HCP selected by a nonrandom quota-based
      convenience sample. No significant differences were found between different HCP
      positions with regard to all collected variables. Approximately 90% acknowledged
      that behavioral issues and health education can affect services. Three-quarters
      of the respondents were aware that a special division was dedicated to adolescent
      medicine. Thirty-seven percent recognized adolescent medicine as a pediatric
      subspecialty and 81% agreed that adolescent reproductive health education and
      promotion are important. This survey showed that health care professionals in the
      Kingdom of Saudi Arabia have a clear perception about the need for specialized
      adolescent health services. Therefore, provision of adolescent health services
      should be supported by health policy-makers.

PMID- 21094439
TI  - Severe obesity and selected risk factors in a sixth grade multiracial cohort: the
      HEALTHY study.
AB  - The purpose of this study was to document the prevalence of severe obesity and
      associated risk in the HEALTHY cohort. A total of 6,365 students were assessed at
      school-based screenings. Results showed that 6.9% of students were severely
      obese. Severe obesity was associated with elevated cardiometabolic risk and
      race/ethnicity. Severe obesity is common and requires preventive intervention.

PMID- 21094441
TI  - Internet use, social networking, and HIV/AIDS risk for homeless adolescents.
AB  - OBJECTIVE: To examine the association between sexual health and internet use,
      including social networking websites such as MySpace and Facebook, among a sample
      of homeless adolescents at high risk of contracting HIV/AIDS. METHODS: In 2009, a
      survey of internet use among 201 homeless adolescents was carried out.
      Multivariate logistic regression models assessed how patterns of use were
      associated with engaging in exchange sex (sex for money, drugs, or housing),
      recent HIV testing, and online partner-seeking behaviors. RESULTS: Among the
      surveyed adolescents, 96.5% reported internet use. Most youth accessed the
      internet at public libraries or youth service agencies. Increased time online and
      recent engagement in exchange sex were both positively associated with online
      partner-seeking. Youth connected to family members online were less likely to
      practice exchange sex and more likely to report a recent HIV test. Youth
      connected to street-based peers online were more likely to practice exchange sex,
      whereas youth connected to home-based peers online were more likely to report a
      recent HIV test. CONCLUSIONS: Although these data are preliminary, homeless youth
      need more access to the internet, as access facilitates connecting with family
      and home-based peers whose presence may reduce sexual risk-taking. Access,
      however, must be carefully monitored to prevent youth soliciting sex online.

PMID- 21094442
TI  - "Stranger in a strange land": the non-address of the 40th president (or is it the
      first?) of the Society for Adolescent Health and Medicine.

PMID- 21094443
TI  - Most recent developments in liver MR imaging. Preface.

PMID- 21094446
TI  - Chronic hepatitis and cirrhosis on MR imaging.
AB  - This article focuses on the current role of magnetic resonance imaging in the
      detection and characterization of chronic hepatitis and cirrhosis. In particular,
      the characteristic MR imaging features of morphologic changes and focal
      manifestations of chronic liver disease are highlighted.

PMID- 21094447
TI  - MR imaging of benign focal liver lesions.
AB  - MRI has become the most important imaging modality for detecting and
      characterizing focal liver lesions. The introduction of high-field-strengths,
      such as 3 Tesla MR imaging, in combination with the parallel imaging technique,
      has led to significant improvements in spatial and temporal resolution and has
      established this technique as a valuable asset in daily clinical practice. New
      techniques, such as diffusion-weighted imaging, may improve MR imaging
      sensitivity and specificity in the diagnostic workup of focal liver lesions. The
      tailored administration of various nonspecific and liver-specific contrast agents
      enables clinicians to increase the detection rate and improve the
      characterization of the different focal liver lesions. This article describes the
      usefulness of these imaging techniques in detecting and characterizing the most
      common benign focal liver lesions.

PMID- 21094444
TI  - Quantification of liver fat with magnetic resonance imaging.
AB  - Intracellular fat accumulation is common feature of liver disease. Intracellular
      fat (steatosis) is the histologic hallmark of nonalcoholic fatty liver disease
      but also may occur with alcohol abuse, viral hepatitis, HIV and genetic
      lipodystrophies, and chemotherapy. This article reviews emerging MR imaging
      techniques that attempt to quantify liver fat. The content provides an overview
      of fatty liver disease and diseases where fat is an important disease feature.
      Also discussed is the current use and limitation of nontargeted biopsy in diffuse
      liver disease and why quantitative noninvasive biomarkers of liver fat would be
      beneficial.

PMID- 21094448
TI  - MR imaging of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy typically associated with
      chronic liver disease and is a leading cause of mortality among these patients.
      Prognosis is improved when detected early. MRI is the best imaging examination
      for accurate diagnosis. Although arterial enhancement with delayed washout,
      increased T2-weighted signal intensity, delayed capsular enhancement, restricted
      diffusion, and tumor thrombus are typical features, not all lesions demonstrate
      these findings. The radiologist must be familiar with these typical imaging
      characteristics, and less common appearances and associated findings of HCC, and
      must be able to differentiate them from those of lesions that mimic HCC.
      Knowledge of therapeutic options and how those are related to imaging findings is
      imperative to assist clinicians in managing these patients.

PMID- 21094445
TI  - Magnetic resonance imaging quantification of liver iron.
AB  - Iron overload is the histologic hallmark of hereditary hemochromatosis and
      transfusional hemosiderosis but also may occur in chronic hepatopathies. This
      article provides an overview of iron deposition and diseases where liver iron
      overload is clinically relevant. Next, this article reviews why quantitative
      noninvasive biomarkers of liver iron would be beneficial. Finally, we describe
      current state-of-the-art methods for quantifying iron with MR imaging and review
      remaining challenges and unsolved problems.

PMID- 21094449
TI  - Diffusion-weighted MRI and liver metastases.
AB  - Liver metastases are the most frequently encountered malignant liver lesions in
      the Western countries. Accurate diagnosis of liver metastases is essential for
      appropriate management of these patients. Multiple imaging modalities, including
      ultrasound, CT, positron emission tomography, and MRI, are available for the
      evaluation of patients with suspected or known liver metastases. Contrast
      enhanced MRI has a high accuracy for detection and characterization of liver
      lesions. Additionally, diffusion-weighted MRI (DWI) has been gaining increasing
      attention. It is a noncontrast technique that is easy to perform, could be
      incorporated in routine clinical protocols, and has the potential to provide
      tissue characterization. This article discusses the basic principles of DWI and
      discusses its emerging role in the detection of liver metastases in patients with
      extrahepatic malignancies.

PMID- 21094450
TI  - Hepatic perfusion imaging: concepts and application.
AB  - Hepatic perfusion imaging with magnetic resonance (MR) imaging is an emerging
      technique for quantitative assessment of diffuse hepatic disease and hepatic
      lesion blood flow. The principal method that has been used is based on T1 dynamic
      contrast-enhanced MR imaging. Perfusion imaging shows promise in the assessment
      of tumor therapy response, staging of liver fibrosis, and evaluation of
      hepatocellular carcinoma. The future standardization of imaging protocols and MR
      imaging pulse sequences will allow for broader clinical applications.

PMID- 21094451
TI  - Magnetic resonance imaging of biliary tumors.
AB  - This article presents current magnetic resonance imaging techniques for the
      diagnosis of biliary tumors. It emphasizes the need for a comprehensive protocol,
      combining imaging sequences of the liver parenchyma and soft tissues with
      magnetic resonance cholangiopancreatography and magnetic resonance angiography to
      detect and stage biliary malignancies. Imaging characteristics that may indicate
      a specific diagnosis are discussed. The potential role of diffusion-weighted
      imaging in diagnosing the cause of biliary obstruction and detecting unsuspected
      nodal disease and peritoneal seeding is emphasized and illustrated.

PMID- 21094452
TI  - Magnetic resonance cholangiopancreatography of benign disorders of the biliary
      system.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is an elegant MR technique for
      noninvasively delineating the biliary system. Technologic advances in MRCP
      acquisition and processing and the routine availability of three-dimensional
      sequences have facilitated detailed assessment of biliary anatomy and pathologic
      or congenital processes; therefore, invasive endoscopic retrograde
      cholangiopancreatography is rarely needed for establishing a diagnosis. MRCP can
      be combined with contrast-enhanced MR imaging to enable concurrent evaluation of
      organs such as the liver and pancreas in addition to functional biliary imaging.
      This review focuses on the current use of MRCP to evaluate nonmalignant processes
      affecting the biliary system.

PMID- 21094453
TI  - MR imaging evaluation of the hepatic vasculature.
AB  - Assessment of the hepatic vasculature is essential for tumor staging, surgical
      planning, and understanding of liver disease. Technological advances have made
      contrast-enhanced magnetic resonance (MR) imaging comparable to multidetector-row
      computed tomography for diagnostic vascular imaging with respect to spatial
      resolution. Unenhanced MR angiographic sequences enable reasonable clinical
      assessment of vessels without contrast agents in patients with contraindications
      or renal insufficiency. Furthermore, MR angiography may be used to provide
      directional information through manipulation of the signal intensity of flowing
      blood. A major limitation to consistent contrast-enhanced MR angiography is the
      timing of MR image acquisition with arrival of the contrast bolus in the
      structures of interest. In this article, the authors discuss currently available
      techniques for imaging of the hepatic vasculature.

PMID- 21094454
TI  - Magnetic resonance imaging of the liver: sequence optimization and artifacts.
AB  - The liver is one of the most challenging organs of the body to image with
      magnetic resonance because it is large and mobile, receives a dual blood supply,
      and is surrounded by organs and structures that contribute to artifacts from flow
      and susceptibility. Recent advances in imaging hardware, in addition to
      improvements in temporal resolution and development of hepatocyte-specific
      contrast agents, make imaging of the liver more approachable than in the past;
      however, it remains a complex process that requires compromise. In this article
      the authors discuss development and optimization of a liver imaging protocol at
      1.5 T, with common variations in each element of the protocol, as well as the
      strengths and weaknesses associated with the relevant sequences.

PMID- 21094455
TI  - Imaging at higher magnetic fields: 3 T versus 1.5 T.
AB  - Clinical hepatobiliary magnetic resonance (MR) imaging continues to evolve at a
      fast rate. However, three basic requirements must still be satisfied if novel
      high-field MR imaging techniques are to be included in the hepatobiliary imaging
      routine: improvement of parenchymal contrast, suppression of respiratory motion
      artifact, and anatomic coverage of the entire hepatobiliary system. This article
      outlines the various arenas involved in MR imaging of the hepatobiliary system at
      3 Tesla (T) compared with 1.5 T by (1) highlighting magnetic field-dependent MR
      contrast phenomena that contribute to the overall appearance of high-field
      hepatobiliary imaging; (2) summarizing the biodistributions of different
      gadolinium chelates used as MR contrast agents and their effectiveness regarding
      the static magnetic field; (3) showing the implementation of advanced imaging
      techniques such as three-dimensional acquisition schemes and parallel
      acceleration techniques used in T1-, T2-, and diffusion-weighted hepatobiliary
      imaging; and (4) addressing artifact mechanisms exacerbated by, or originating
      from, increase of the static magnetic field.

PMID- 21094456
TI  - Functional magnetic resonance imaging of the liver: parametric assessments beyond
      morphology.
AB  - There is growing interest in exploring and using functional imaging techniques to
      provide additional information on structural alterations in the liver, which
      often occur late in the disease process. This article presents a summary of the
      different functional MR imaging techniques currently in use, focusing on dynamic
      contrast-enhanced MR imaging, diffusion-weighted MR imaging, MR spectroscopy, in-
      and oppose-phase MR imaging, and T2*-weighted imaging. For each technique, the
      biologic underpinning for the technique is explained, the clinical applications
      surveyed, and the challenges for their application enumerated. Developing and
      less frequently used techniques such as MR elastography, blood oxygenation level
      dependent imaging, dynamic susceptibility contrast-enhanced MR imaging, and
      diffusion-tensor imaging are reviewed. The challenges widespread adoption of
      functional MR imaging and the translation of such techniques to high field
      strengths are also discussed.

PMID- 21094457
TI  - Tumors of the liver and intrahepatic bile ducts: radiologic-pathologic
      correlation.
AB  - Primary tumors of the liver can be classified pathologically based on their cell
      of origin into epithelial tumors, arising from hepatocytes or biliary epithelium,
      and nonepithelial tumors, including mesenchymal tumors and lymphoma.
      Characteristic findings on MR imaging can be seen in many cases. This article
      reviews the MR imaging appearance of these tumors with pathologic correlation.

PMID- 21094458
TI  - Hooked on Hes: a T-ALL of addiction.
AB  - Hes1 is a direct Notch1 target; however, its precise function is unclear. In this
      issue of Immunity, Wendorff et al. (2010) report that Hes1 regulates the number
      of T cell progenitors and has important functions in both the induction and
      maintenance of T cell leukemia.

PMID- 21094459
TI  - Licensing PPARgamma to work in macrophages.
AB  - The mechanisms that direct cell-type-specific peroxisome proliferator-activated
      receptor (PPAR) gene programs are poorly understood. In this issue of Immunity,
      Szanto et al. (2010) identify signal transducer and activator of transcription 6
      as a transcriptional switch that licenses PPARgamma-dependent gene expression in
      macrophages and dendritic cells.

PMID- 21094460
TI  - The LTi cell, an immunologic chameleon.
AB  - Lymphoid tissue inducer (LTi) cells are key components of the machinery required
      for the construction of the lymphoid structures underlying immune responses. In
      this issue of Immunity, Vonarbourg et. al. (2010) describe how these cells assume
      several different guises, each associated with different LTi functions.

PMID- 21094461
TI  - Infected cell in trouble: bystander cells ring the bell.
AB  - Infection with intracellular pathogens triggers cytokine production in the
      infected cells. In this issue of Immunity, Kasper et al. (2010) demonstrate that
      in certain infections, much of the response is mounted by noninfected neighboring
      cells.

PMID- 21094462
TI  - Trapped versus soluble chemokines: functions in leukocyte adhesion and motility.
AB  - In this issue of Immunity, Bao et al. (2010) provide in vivo evidence that
      heparan sulfate glycosaminoglycans (GAGs) are indispensable for immobilization
      and function of major chemokines required for leukocyte adhesion to and crossing
      through blood and lymphatic vessels.

PMID- 21094463
TI  - Neutrophils, from marrow to microbes.
AB  - Neutrophils are produced in the bone marrow from stem cells that proliferate and
      differentiate to mature neutrophils fully equipped with an armory of granules.
      These contain proteins that enable the neutrophil to deliver lethal hits against
      microorganisms, but also to cause great tissue damage. Neutrophils circulate in
      the blood as dormant cells. At sites of infection, endothelial cells capture
      bypassing neutrophils and guide them through the endothelial cell lining whereby
      the neutrophils are activated and tuned for the subsequent interaction with
      microbes. Once in tissues, neutrophils kill microorganisms by microbicidal agents
      liberated from granules or generated by metabolic activation. As a final act,
      neutrophils can extrude stands of DNA with bactericidal proteins attached that
      act as extracellular traps for microorganisms.

PMID- 21094464
TI  - Basal insulin dose in 40 type 1 diabetic patients remains stable 1 year after
      educational training in flexible insulin therapy.
AB  - AIM: Basal insulin dose (BID) determination is the key to successful flexible
      insulin therapy (FIT). As our hypothesis was that BID changes over time, the
      primary objective of the present study was to determine the changes in BID 1 year
      after a therapeutic educational programme on FIT. METHODS: This single-centre
      retrospective study recruited the first 40 type 1 adult diabetic patients
      undergoing an educational FIT programme, which was conducted over a 4-day
      hospital stay and included a carbohydrate-fasting test. RESULTS: Patients' BIDs
      decreased between Day 0 and Day 4 after the programme (0.31+/-0.11IU/kg/day vs
      0.27+/-0.09IU/kg/day; P<0.0001), and was increased at 1 year (0.29+/
      0.09IU/kg/day; P=0.004). There was no significant variation in prandial insulin
      requirements. A tendency toward a reduction in HbA(1c) was observed at 1 year
      (8.3+/-1.4% vs 8.1+/-1.6%; P=0.075), with a decrease by more than 0.5% in 37.5%
      of patients. Body weight increased at 1 year (66.9+/-10.4 kg vs 68.1+/-10.7 kg;
      P=0.003), and the gain was greater than 5% in 7.5% of patients. Frequency of mild
      hypoglycaemia either remained stable (40%) or decreased (30%). Only nine patients
      (baseline HbA(1c) 8.03+/-1.7%, baseline BID 0.27+/-0.09IU/kg/day) had BID
      increases more than 20%, with no changes in prandial insulin requirements and no
      distinctive phenotype. Baseline HbA(1c), and BID have an impact on the BID at 1
      year of approximately 0.3IU/kg/day in most patients. CONCLUSION: The stability of
      BID over 1 year, with values close to 0.3IU/kg/day associated with a trend
      towards improvement in HbA(1c), reduction in the frequency of mild hypoglycaemic
      episodes and absence of major weight gain, supports the relevance of FIT
      educational training.

PMID- 21094465
TI  - Spontaneous resolution of tetraparesis because of postoperative cervical epidural
      hematoma.
AB  - BACKGROUND CONTEXT: Symptomatic postoperative spinal epidural hematoma (PSEH) is
      a rare but potentially devastating postoperative complication, accounting for
      0.1% to 0.2% of cases. PURPOSE: To describe a patient with a PSEH that completely
      resolved, clinically and radiographically, without surgical treatment. STUDY
      DESIGN: Case report and review of the literature. METHODS: A 47-year-old man with
      no history of a bleeding disorder underwent anterior cervical interbody fusion
      for C5-C6 disc herniation. The dura was exposed through removal of the posterior
      longitudinal ligament, and extensive decompression of posterior osteophytes of C5
      and C6 vertebral bodies was performed. The patient developed tetraparesis and
      respiratory distress rapidly in the postanesthesia care unit and was reintubated
      for assisted ventilation. The computed tomography (CT) scan revealed a very large
      ventral epidural hematoma compressing the dural sac from C1 to C6. RESULTS: The
      patient was prepared for hematoma evacuation. However, the neurological symptoms
      and respiration problems began to resolve spontaneously before the surgery was
      started. The hematoma was markedly improved on the follow-up CT scan, and the
      patient was discharged 2 weeks after surgery without neurological deficit.
      CONCLUSIONS: This case illustrates that an unpredictable extensive hematoma can
      occur after uneventful surgery of the cervical spine in low-risk patients. In
      case of the dural exposure with a creation of hidden and large epidural space,
      the spine surgeon must pay particular attention to the possibility of a PSEH
      during the early postoperative period.

PMID- 21094466
TI  - Spine care at a crossroads.

PMID- 21094467
TI  - Dural repair with four spinal sealants: focused review of the manufacturers'
      inserts and the current literature.
AB  - BACKGROUND CONTEXT: Deliberate or traumatic dural fistulas are typically
      augmented by a "sealant" or "fibrin glue" to enhance the strength of dural
      closure. PURPOSE: Little is known about the risks and complications associated
      with two specific "sealants" and two specific "fibrin glues" used for dural
      closure. STUDY DESIGN/SETTING: Review of the manufacturers' inserts and a focused
      review of the literature concerning the pros and cons for two "sealants"
      (DuraSeal [Confluent Surgical Inc., Waltham, MA, USA] and BioGlue [Cryolife,
      Kennesaw, GA, USA]) and two "fibrin glues" (EVICEL [Johnson and Johnson Wound
      Management, Ethicon Inc., Somerville, NJ, USA] and Tisseel [fibrin sealant;
      Baxter International Inc., Westlake Village, CA, USA]) were assessed. PATIENT
      SAMPLE: A focused review of the literature using four different "sealants" or
      "fibrin glues" was performed. OUTCOME MEASURES: Documentation of
      persistent/recurrent postoperative cerebrospinal fluid fistulas was an end point
      for failure for the four different "sealants" and "fibrin glues." METHODS:
      Manufacturers' inserts and a focused review of the literature concerning the
      relative safety and efficacy of two "sealants" (DuraSeal and BioGlue) and two
      "fibrin glues" (EVICEL and Tisseel) used to augment dural closure were assessed.
      RESULTS: Although DuraSeal is approved by the Federal Drug Administration (FDA)
      for intracranial and spinal application, two instances of paralysis are described
      in the literature. BioGlue is classified by the manufacturer as neurotoxic.
      EVICEL, one of the "fibrin glues," appeared in just two animal studies, whereas
      Tisseel, the other "fibrin glue," has been used in many large clinical series
      without adverse events. CONCLUSION: Despite the lack of FDA approval, Tisseel
      (fibrin glue) has seen wide adoption in "off-label" use. DuraSeal, which is FDA
      approved, was associated with two instances of paralysis. Alternatively, BioGlue
      was described as neurotoxic even by the manufacturer.

PMID- 21094468
TI  - Reduction in segmental flexibility because of disc degeneration is accompanied by
      higher changes in facet loads than changes in disc pressure: a poroelastic C5-C6
      finite element investigation.
AB  - BACKGROUND CONTEXT: Nerve fiber growth inside the degenerative intervertebral
      discs and facets is thought to be a source of pain, although there may be several
      other pathological and clinical reasons for the neck pain. It, however, remains
      difficult to decipher how much disc and facet joints contribute to overall
      degenerative segmental responses. Although the biomechanical effects of disc
      degeneration (DD) on segmental flexibility and posterior facets have been
      reported in the lumbar spine, a clear understanding of the pathways of
      degenerative progression is still lacking in the cervical spine. PURPOSE: To test
      the hypothesis that after an occurrence of degenerative disease in a cervical
      disc, changes in the facet loads will be higher than changes in the disc
      pressure. STUDY DESIGN: To understand the biomechanical relationships between
      segmental flexibility, disc pressure, and facet loads when the C5-C6 disc
      degenerates. METHODS: A poroelastic, three-dimensional finite element (FE) model
      of a normal C5-C6 segment was developed and validated. Two degenerated disc
      models (moderate and severe) were built from the normal disc model. Biomechanical
      responses of the three FE models (normal, moderate, and severe) were further
      studied under diurnal compression (at the end of the daytime activity period) and
      moment loads (at the end of 5 seconds) in terms of disc height loss, angular
      motions, disc pressure, and facet loads (average of right and left facets).
      RESULTS: Disc deformation under compression and segmental rotational motions
      under moment loads for the normal disc model agreed well with the corresponding
      in vivo studies. A decrease in segmental flexibility because of DD is accompanied
      by a decrease in disc pressure and an increase in facet loads. Biomechanical
      effects of degenerative disc changes are least in flexion. Segmental flexibility
      changes are higher in extension, whereas changes in disc pressure and facet loads
      are higher in lateral bending and axial rotation, respectively. CONCLUSIONS: The
      results of the present study confirmed the hypothesis of higher changes in facet
      loads than in disc pressure, suggesting posterior facets are more affected than
      discs because of a decrease in degenerative segmental flexibility. Therefore, a
      degenerated disc may increase the risk of overloading the posterior facet joints.
      It should be clearly noted that only after degeneration simulation in the disc,
      we recorded the biomechanical responses of the facets and disc. Therefore, our
      hypothesis does not suggest that facet joint osteoarthritis may occur before
      degeneration in the disc. Future cervical spine-based experiments are warranted
      to verify the conclusions presented in this study.

PMID- 21094469
TI  - Effects of rate of loading on viscoelastic supraspinous ligament inflammation and
      cumulative lumbar disorder.
AB  - COMMENTARY ON: Pinski SE, King KB, Davidson BS, et al. High-frequency loading of
      lumbar ligaments increases proinflammatory cytokines expression in a feline model
      of repetitive musculoskeletal disorder. Spine J 2010:10:1078-85 (in this issue).

PMID- 21094470
TI  - Does a needle puncture into the annulus fibrosus cause disc degeneration?
AB  - COMMENTARY ON: Michalek AJ, Buckley MR, Bonassar LJ, et al. The effects of needle
      puncture injury on microscale shear strain in the intervertebral disc annulus
      fibrosus. Spine J 2010:10:1098-105 (in this issue).

PMID- 21094471
TI  - Recurrent autonomic dysreflexia exacerbates vascular dysfunction after spinal
      cord injury.
AB  - BACKGROUND CONTEXT: Individuals with high spinal cord injury (SCI) are prone to
      significant fluctuation in blood pressure with episodes of very high and low
      blood pressure during autonomic dysreflexia (AD) and orthostatic hypotension,
      respectively. We do not know how such blood pressure lability affects the
      vasculature. PURPOSE: We used a well-characterized animal model of AD to
      determine whether increasing the frequency of AD during recovery from SCI would
      exacerbate injury-induced dysfunction in resistance vessels. STUDY
      DESIGN/SETTING: Experimental animal study. International Collaboration On Repair
      Discoveries (ICORD), University of British Columbia, Canada. METHODS: Complete
      transection of the T3 spinal cord was performed in male Wistar rats. For 14 days
      after injury, AD was induced via colorectal distension (CRD; 30 minutes per day)
      in the experimental group (SCI-CRD). One month after SCI, baseline cardiovascular
      parameters and severity of CRD-induced AD were assessed in SCI-CRD animals and
      SCI-only controls. Mesenteric arteries were harvested for in vitro myography to
      characterize vasoactive responses to phenylephrine (PE) and acetylcholine (ACh).
      RESULTS: Mesenteric arteries from SCI-CRD animals exhibited larger maximal
      responses to PE than arteries from SCI-only controls. Hyperresponsiveness to PE
      was not a product of endothelial dysfunction because mesenteric arteries from
      both groups had similar vasodilator responses to ACh. Both SCI-only controls and
      SCI-CRD animals exhibited CRD-evoked AD 1 month after SCI; however, CRD-induced
      hypertension was less pronounced in animals that were previously exposed to CRD.
      CONCLUSIONS: Injury-induced changes within the vasculature may contribute to the
      development of AD after SCI. Here, we provide evidence that AD itself has
      significant and long-lasting effects on vascular function. This finding has
      implications for the medical management of AD and provides an impetus for
      maintaining stable blood pressure.

PMID- 21094472
TI  - A pictorial classification atlas of cement extravasation with vertebral
      augmentation.
AB  - BACKGROUND CONTEXT: Minimally invasive procedures for the treatment of vertebral
      compression fractures (VCFs) have been in use since the mid-1980s. A mixture of
      liquid monomer and powder is introduced through a needle into one or both
      pedicles, and it polymerizes within the vertebral body in an exothermic chemical
      reaction. The interaction between cement and the fractured vertebral body
      determines whether and how the cement stabilizes the fragments, alters
      morphology, and extravasates. The cement is intended to remain within the
      vertebral body. However, some studies have reported cement leakage in more than
      80% of the procedures. Although cement leakage can have no or minimal clinical
      consequences, adverse events, such as paraplegia, spinal cord and nerve root
      compression, cement pulmonary embolisms, or death, can occur. The details of how
      the cement infiltrates a vertebral body or extravasates out of the body are
      poorly understood and may help to identify strategies to reduce complications and
      improve clinical efficacy. PURPOSE: Apply novel techniques to demonstrate the
      cement spread inside vertebrae as well as the points and pattern of cement
      extravastation. STUDY DESIGN: Ex vivo assessment of vertebral augmentation
      procedures. METHODS: Vertebrae from six fresh whole human cadaver spines were
      used to create 24 specimens of three vertebrae each. The specimens were placed in
      a pneumatic testing system, designed to create controlled anterior wedge
      compression fractures. Unipedicular augmentation was performed on the central
      vertebra of 24 specimens using polymethylmethacrylate/barium sulfate
      Vertebroplastic cements (DePuy Spine, Raynham, MA, USA). The volume of cement
      injected into each vertebra was recorded. Fine-cut computed tomography (CT) scans
      of all segments were obtained (Brilliance 64; Philips Medical Imaging, Amsterdam,
      The Netherlands). Using multiplanar reconstructions and volume compositing three
      dimensional imaging (Osirix, www.osirix-viewer.com), each specimen was carefully
      assessed for cement extravasation. Specimens were then immersed in a 50% sodium
      hypochlorite solution until all overlying soft tissues were removed, leaving the
      bone and cement intact. The specimens were dried and visually examined and
      photographed to assess cement extravasation and fracture patterns. Specimens were
      cut in the axial or sagittal plains to assess the gross morphology of cement
      infiltration and extravasation. Finally, 25-mm block sections were removed from
      selected specimens and imaged at 14-MUm resolution using a GE Locus-SP micro-CT
      system (GE Healthcare, London, Ontario, Canada). RESULTS: Infiltration was
      characterized by an intimate capture of trabecular bone within the cement,
      forming an irregular border at the perimeter of the cement that is determined by
      the morphology of the trabeculae and marrow spaces. Extravasation of the cement
      was assessed as "any" if any small or large amount of extravastation was detected
      and was also assessed as severe if a large amount of extravasation was found. Out
      of the 23 levels studied, some extravasation was visibly apparent in all levels.
      A wide spectrum of filling patterns, leakage points, and interdigitation of the
      cement was observed and appeared to be determined by the interaction of the
      cement with the trabecular morphology. The results support the fact that the
      cement generally advances through the vertebrae with relatively regular and
      easily identifiable borders. CONCLUSIONS: Using a cadaver VCF model, this study
      demonstrated the exact filling and extravastation patterns of bone cement inside
      and out of fractured vertebrae. These data enhance our understanding of the
      vertebral augmentation and extravastation mechanics.

PMID- 21094474
TI  - The words we use.

PMID- 21094473
TI  - The association of occipitocervical dissociation and death as a result of blunt
      trauma.
AB  - BACKGROUND CONTEXT: Despite multiple reports of survivability, dissociative
      occipitocervical injury (OCI) is generally accepted to be fatal in most cases.
      The actual number of trauma victims where OCI may have made the difference
      between life and death is unknown because multiple studies have shown that these
      injuries can be missed with current diagnostic methods. An improved understanding
      of the relative importance of OCI in blunt trauma mortality may help to refine
      protocols for the assessment and treatment of patients who arrive alive to the
      emergency room after severe blunt trauma. One way to improve our understanding is
      to document the relative frequency OCI relative to brain, liver, aorta, and
      spleen injuries in blunt trauma fatalities. PURPOSE: In this study, we aimed to
      glean a more accurate estimate of the absolute and relative incidence of OCI
      after death from blunt trauma via a systematic review of data reported in the
      forensic literature. STUDY DESIGN: Systematic literature review. METHODS: A
      systematic literature search and review were undertaken. The search aimed to
      answer three primary questions: What is the true incidence of cervical spine
      injuries in blunt trauma fatalities? What is the incidence of dissociative OCIs
      specifically? and What is the incidence of these injuries relative to other
      common injuries associated with blunt trauma fatalities (central nervous system,
      spleen, liver, etc)? For that, two search protocols were used and included
      postmortem studies of blunt trauma mechanism in adult population. RESULTS: The
      mean reported incidence of cervical spine injuries was 49.7% in blunt trauma
      fatalities. Dissociative OCIs were found to have a mean incidence of 18.1%. The
      relative frequencies of injuries were 49.7% for cervical spine, 41.8% for central
      nervous system, 20.8% for liver, 11.2% for spleen, and 10.8% for aorta.
      CONCLUSIONS: In this systematic literature review, cervical spine injuries were
      found to be the most commonly reported finding associated with blunt trauma
      fatalities, occurring in nearly 50% of cases with occipitocervical dissociation
      accounting for nearly 20%. Older pathologic studies suggested a lesser overall
      and relative frequency and may have underestimated their incidence. Typically,
      these blunt cervical spine injuries were much more commonly found to disrupt the
      soft tissue stabilizing restraints (ligaments, facet capsules, etc) as opposed to
      causing bony fractures and, accordingly, were often not detected on plain
      radiographs. It is likely that the frequency of this injury is underestimated in
      patients surviving severe blunt trauma, placing them at risk for death from an
      occult source in the postinjury period. Additional research is needed to
      determine if improved methods to diagnose OCI and improved patient management
      protocols to protect against secondary injuries might reduce mortality in blunt
      trauma victims.

PMID- 21094475
TI  - The bond strength of the resin-to-zirconia interface using different bonding
      concepts.
AB  - OBJECTIVES: This study investigated the shear bond strength (SBS) and the tensile
      bond strength (TBS) of the zirconia-to-resin interface using different cement
      bonding concepts. METHODS: Coplanar zirconia specimens were bonded to CoCr
      cylinders measuring 5 mm in diameter and 3 mm in height. All bonding areas were
      first sandblasted with 110 MUm Al(2)O(3) (0.28 MPa, 10 s). SBS and TBS were
      determined after 24 h and 90 d of water storage as well as after 12,000 thermal
      cycles (TC, 5 degrees /55  degrees C, 17 d). The bonding concepts consisted of
      the application of a silane coupling agent, tribological silica coating (Rocatec
      system), cements or primers containing phosphone, mono-phosphate, or di
      phosphate, and a combination of silica coating and primer. RESULTS: Bond strength
      higher than 10 MPa was considered clinically sufficient. SBS measured with each
      bonding concept surpassed this value, except control and MaxCem after 90 d. In
      contrast, TBS values were rather different. The application of a silane coupling
      agent alone showed very low values in the TBS test. Silica coating was only
      sufficient after 90 d of water storage and when combined with phosphate-esters or
      phosphone-containing primers. Bonding agents based on di-phosphates or phosphones
      showed stable TBS values of less than 10 MPa under different aging conditions.
      The predominant mode of failure was adhesive failure at the ceramic surface.
      CONCLUSIONS: None of the investigated bonding concepts of the zirconia-to-resin
      interface provided clinically sufficient tensile bond strength. SBS values were
      inadequate for a sufficient ranking.

PMID- 21094476
TI  - Abrupt increase in rat carotid blood flow induces rapid alteration of artery
      mechanical properties.
AB  - Vascular remodeling is essential to proper vessel function. Dramatic changes in
      mechanical environment, however, may initiate pathophysiological vascular
      remodeling processes that lead to vascular disease. Previous work by some of our
      group has demonstrated a dramatic rise in matrix metalloproteinase (MMP)
      expression shortly following an abrupt increase in carotid blood flow. We
      hypothesized that there would be a corresponding change in carotid mechanical
      properties. Unilateral carotid ligation surgery was performed to produce an
      abrupt, sustained increase in blood flow through the contralateral carotid artery
      of rats. The flow-augmented artery was harvested after sham surgery or 1, 2, or 6
      days after flow augmentation. Vessel mechanical response in the circumferential
      direction was then evaluated through a series of pressure-diameter tests. Results
      show that the extent of circumferential stretch (normalized change in diameter)
      at in vivo pressure levels was significantly different (p<0.05) from normo-flow
      controls at 1 and 2 days following flow augmentation. Measurements at 1, 2, and 6
      days were not significantly different from one another, but a trend in the data
      suggested that circumferential stretch was largest 1 day following surgery and
      subsequently decreased toward baseline values. Because previous work with this
      model indicated a similar temporal pattern for MMP-9 expression, an exploratory
      set of experiments was conducted where vessels were tested 1 day following
      surgery in animals treated with broad spectrum MMP inhibitors (either doxycycline
      or GM6001). Results showed a trend for the inhibitors to minimize changes in
      mechanical properties. Observations demonstrate that vessel mechanical properties
      change rapidly following flow augmentation and that alterations may be linked to
      expression of MMPs.

PMID- 21094477
TI  - Investigation of the material properties of alginate for the development of
      hydrogel repair of dura mater.
AB  - The collagenous dura mater isolates the brain from the external environment and
      requires a secure closure following invasive neurosurgery. This is typically
      accomplished by approximation of the dura mater via sutures and adhesives. In
      selected cases, however, large portions of dura mater require excision,
      necessitating a tissue replacement patch. The mild reaction conditions and long
      term biocompatibility of alginate evince strong candidacy for these applications.
      This study investigates the potential of diffusion and internally gelled
      alginates for these applications. Specifically, we quantified the viscosity, gel
      rate, syneresis level, compressive strength, compressive modulus, complex modulus
      and loss angle in the context of dura mater repair. The ideal sealant would have
      a rapid cross-link speed, while the ideal dura mater replacement would have a low
      level of syneresis. Both applications require a compressive modulus of 20-100 kPa
      and a complex modulus of 1-24 kPa. The data collected in this study suggests that
      the use of 1.95 wt% 43 mPa s alginate with 200 mM CaCl(2) is sufficient for
      approximating the dural membrane for closure alone or in conjunction with suture.
      Alternatively, the use of 1.95 wt% 43 mPa s alginate with 100 mM CaCO(3) is
      sufficient for tissue replacement in large dural defects.

PMID- 21094479
TI  - Boron nitride nanotube reinforced hydroxyapatite composite: mechanical and
      tribological performance and in-vitro biocompatibility to osteoblasts.
AB  - This study proposes boron nitride nanotube (BNNT) reinforced hydroxyapatite (HA)
      as a novel composite material for orthopedic implant applications. The spark
      plasma sintered (SPS) composite structure shows higher density compared to HA.
      Minimal lattice mismatch between HA and BNNT leads to coherent bonding and strong
      interface. HA-4 wt% BNNT composite offers excellent mechanical properties-120%
      increment in elastic modulus, 129% higher hardness and 86% more fracture
      toughness, as compared to HA. Improvements in the hardness and fracture toughness
      are related to grain refinement and crack bridging by BNNTs. HA-BNNT composite
      also shows 75% improvement in the wear resistance. The wear morphology suggests
      localized plastic deformation supported by the sliding of outer walls of BNNT.
      Osteoblast proliferation and cell viability show no adverse effect of BNNT
      addition. HA-BNNT composite is, thus, envisioned as a potential material for
      stronger orthopedic implants.

PMID- 21094478
TI  - Measuring the dynamic mechanical response of hydrated mouse bone by
      nanoindentation.
AB  - This study demonstrates a novel approach to characterizing hydrated bone's
      viscoelastic behavior at lamellar length scales using dynamic indentation
      techniques. We studied the submicron-level viscoelastic response of bone tissue
      from two different inbred mouse strains, A/J and B6, with known differences in
      whole bone and tissue-level mechanical properties. Our results show that bone
      having a higher collagen content or a lower mineral-to-matrix ratio demonstrates
      a trend towards a larger viscoelastic response. When normalized for anatomical
      location relative to biological growth patterns in the antero-medial (AM) cortex,
      bone tissue from B6 femora, known to have a lower mineral-to-matrix ratio, is
      shown to exhibit a significantly higher viscoelastic response compared to A/J
      tissue. Newer bone regions with a higher collagen content (closer to the
      endosteal edge of the AM cortex) showed a trend towards a larger viscoelastic
      response. Our study demonstrates the feasibility of this technique for analyzing
      local composition-property relationships in bone. Further, this technique of
      viscoelastic nanoindentation mapping of the bone surface at these submicron
      length scales is shown to be highly advantageous in studying subsurface features,
      such as porosity, of wet hydrated biological specimens, which are difficult to
      identify using other methods.

PMID- 21094480
TI  - Effects of age and loading rate on equine cortical bone failure.
AB  - Although clinical bone fractures occur predominantly under impact loading (as
      occurs during sporting accidents, falls, high-speed impacts or other catastrophic
      events), experimentally validated studies on the dynamic fracture behavior of
      bone, at the loading rates associated with such events, remain limited. In this
      study, a series of tests were performed on femoral specimens obtained post-mortem
      from equine donors ranging in age from 6 months to 28 years. Fracture toughness
      and compressive tests were performed under both quasi-static and dynamic loading
      conditions in order to determine the effects of loading rate and age on the
      mechanical behavior of the cortical bone. Fracture toughness experiments were
      performed using a four-point bending geometry on single and double-notch
      specimens in order to measure fracture toughness, as well as observe differences
      in crack initiation between dynamic and quasi-static experiments. Compressive
      properties were measured on bone loaded parallel and transverse to the osteonal
      growth direction. Fracture propagation was then analyzed using scanning electron
      and scanning confocal microscopy to observe the effects of microstructural
      toughening mechanisms at different strain rates. Specimens from each horse were
      also analyzed for dry, wet and mineral densities, as well as weight percent
      mineral, in order to investigate possible influences of composition on mechanical
      behavior. Results indicate that bone has a higher compressive strength, but lower
      fracture toughness when tested dynamically as compared to quasi-static
      experiments. Fracture toughness also tends to decrease with age when measured
      quasi-statically, but shows little change with age under dynamic loading
      conditions, where brittle "cleavage-like" fracture behavior dominates.

PMID- 21094481
TI  - Dynamic compressive response of bovine liver tissues.
AB  - This study aims to experimentally determine the strain rate effects on the
      compressive stress-strain behavior of bovine liver tissues. Fresh liver tissues
      were used to make specimens for mechanical loading. Experiments at quasi-static
      strain rates were conducted at 0.01 and 0.1 s(-1). Intermediate-rate experiments
      were performed at 1, 10, and 100 s(-1). High strain rate (1000, 2000, and 3000 s(
      1)) experiments were conducted using a Kolsky bar modified for soft material
      characterization. A hollow transmission bar with semi-conductor strain gages was
      used to sense the weak forces from the soft specimens. Quartz-crystal force
      transducers were used to monitor valid testing conditions on the tissue
      specimens. The experiment results show that the compressive stress-strain
      response of the liver tissue is non-linear and highly rate-sensitive, especially
      when the strain rate is in the Kolsky bar range. The tissue stiffens
      significantly with increasing strain rate. The responses from liver tissues along
      and perpendicular to the liver surface were consistent, indicating isotropic
      behavior.

PMID- 21094482
TI  - Application of finite element analysis to the design of tissue leaflets for a
      percutaneous aortic valve.
AB  - Percutaneous Aortic Valve (PAV) replacement is an attractive alternative to open
      heart surgery, especially for patients considered to be poor surgical candidates.
      Despite this, PAV replacement still has its limitations and associated risks.
      Bioprosthetic heart valves still have poor long-term durability due to
      calcification and mechanical failure. In addition, the implantation procedure
      often presents novel challenges, including damage to the expandable stents and
      bioprosthetic leaflets. In this study, a simplified version of Fung's elastic
      constitutive model for skin, developed by Sun and Sacks, was implemented using
      finite element analysis (FEA) and applied to the modelling of bovine and kangaroo
      pericardium. The FEA implementation was validated by simulating biaxial tests and
      by comparing the results with experimental data. Concepts for different PAV
      geometries were developed by incorporating valve design and performance
      parameters, along with stent constraints. The influence of effects such as
      different leaflet material, material orientation and abnormal valve dilation on
      the valve function was investigated. The stress distribution across the valve
      leaflet was also examined to determine the appropriate fibre direction for the
      leaflet. The simulated attachment forces were compared with suture tearing tests
      performed on the pericardium to evaluate suture density. It is concluded that
      kangaroo pericardium is suitable for PAV applications, and superior to bovine
      pericardium, due to its lower thickness and greater extensibility.

PMID- 21094483
TI  - Mechanical characteristics of an Ormocomp((r)) biocompatible hybrid photopolymer.
AB  - In this work, the mechanical behaviour of a photocured Ormocomp((r)) hybrid
      material is investigated. Its biocompatible nature has attracted a growing
      interest for microfabrication applications in biomedicine and tissue engineering.
      Measurements of in situ solidification strain development and achieved degree of
      curing, as obtained using a fibre optic sensor, are presented. The results show
      that the solidification strains generated during UV-curing are significant at the
      maximum achieved degree of curing. The mechanical response (Young's modulus) of
      the material was investigated by testing of thin-film and regular size specimens.
      It was found that the measured mean elastic modulus of the thin-film specimens
      was of the same order of magnitude as that of the larger specimens but noticeably
      smaller.

PMID- 21094484
TI  - Biomechanical comparison of implant retained fixed partial dentures with fiber
      reinforced composite versus conventional metal frameworks: a 3D FEA study.
AB  - Fiber reinforced composite (FRC) materials have been successfully used in a
      variety of commercial applications. These materials have also been widely used in
      dentistry. The use of fiber composite technology in implant prostheses has been
      previously presented, since they may solve many problems associated with metal
      alloy frameworks such as corrosion, complexity of fabrication and high cost. The
      hypothesis of this study was that an FRC framework with lower flexural modulus
      provides more even stress distribution throughout the implant retained fixed
      partial dentures (FPDs) than a metal framework does. A 3-dimensional finite
      element analysis was conducted to evaluate the stress distribution in bone,
      implant-abutment complex and prosthetic structures. Hence, two distinctly
      different models of implant retained 3-unit fixed partial dentures, composed of
      Cr-Co and porcelain (M-FPD model) or FRC and particulate composite (FRC-FPD
      model) were utilized. In separate load cases, 300 N vertical, 150 N oblique and
      60 N horizontal forces were simulated. When the FRC-FPD and M-FPD models were
      compared, it was found that all investigated stress values in the M-FPD model
      were higher than the values in the FRC-FPD model except for the stress values in
      the implant-abutment complex. It can be concluded that the implant supported FRC
      FPD could eliminate the excessive stresses in the bone-implant interface and
      maintain normal physiological loading of the surrounding bone, therefore
      minimizing the risk of peri-implant bone loss due to stress-shielding.

PMID- 21094485
TI  - Analysis of laser fabricated microjoint performance in cerebrospinal fluid using
      a computational approach.
AB  - Assessment of neural biocompatibility requires that materials be tested with
      exposure in neural fluids. We have studied the mechanical performance of laser
      bonded microjoints between titanium foil and polyimide film (TiPI) in artificial
      cerebrospinal fluid (CSF). The samples were exposed in CSF for two, four and
      twelve weeks at 37  degrees C. The laser microbonds showed initial degradation up
      to four weeks which then stabilized afterwards and retained similar strength
      until twelve weeks. To understand this bond degradation mechanism better, a
      finite element modeling approach was adopted. From the finite element results, it
      was revealed that bond degradation was not due to the hygroscopic expansion of
      polyimide. Rather, relaxation of the process induced residual stresses may have
      resulted in weakening of the bond strength as observed from experimental
      measurements.

PMID- 21094486
TI  - Recent progress in biopolymer nanoparticle and microparticle formation by heat
      treating electrostatic protein-polysaccharide complexes.
AB  - Functional biopolymer nanoparticles or microparticles can be formed by heat
      treatment of globular protein-ionic polysaccharide electrostatic complexes under
      appropriate solution conditions. These biopolymer particles can be used as
      encapsulation and delivery systems, fat mimetics, lightening agents, or texture
      modifiers. This review highlights recent progress in the design and fabrication
      of biopolymer particles based on heating globular protein-ionic polysaccharide
      complexes above the thermal denaturation temperature of the proteins. The
      influence of biopolymer type, protein-polysaccharide ratio, pH, ionic strength,
      and thermal history on the characteristics of the biopolymer particles formed is
      reviewed. Our current understanding of the underlying physicochemical mechanisms
      of particle formation and properties is given. The information provided in this
      review should facilitate the rational design of biopolymer particles with
      specific physicochemical and functional attributes, as well as stimulate further
      research in identifying the physicochemical origin of particle formation.

PMID- 21094487
TI  - Colloidal interactions and fouling of NF and RO membranes: a review.
AB  - Colloids are fine particles whose characteristic size falls within the rough size
      range of 1-1000 nm. In pressure-driven membrane systems, these fine particles
      have a strong tendency to foul the membranes, causing a significant loss in water
      permeability and often a deteriorated product water quality. There have been a
      large number of systematic studies on colloidal fouling of reverse osmosis (RO)
      and nanofiltration (NF) membranes in the last three decades, and the
      understanding of colloidal fouling has been significantly advanced. The current
      paper reviews the mechanisms and factors controlling colloidal fouling of both RO
      and NF membranes. Major colloidal foulants (including both rigid inorganic
      colloids and organic macromolecules) and their properties are summarized. The
      deposition of such colloidal particles on an RO or NF membrane forms a cake
      layer, which can adversely affect the membrane flux due to 1) the cake layer
      hydraulic resistance and/or 2) the cake-enhanced osmotic pressure. The effects of
      feedwater compositions, membrane properties, and hydrodynamic conditions are
      discussed in detail for inorganic colloids, natural organic matter,
      polysaccharides, and proteins. In general, these effects can be readily explained
      by considering the mass transfer near the membrane surface and the colloid
      membrane (or colloid-colloid) interaction. The critical flux and limiting flux
      concepts, originally developed for colloidal fouling of porous membranes, are
      also applicable to RO and NF membranes. For small colloids (diameter?100 nm), the
      limiting flux can result from two different mechanisms: 1) the diffusion
      solubility (gel formation) controlled mechanism and 2) the surface interaction
      controlled mechanism. The former mechanism probably dominates for concentrated
      solutions, while the latter mechanism may be more important for dilute solutions.
      Future research needs on RO and NF colloidal fouling are also identified in the
      current paper.

PMID- 21094488
TI  - Novel approaches to the study of postmortem brain in psychiatric illness: old
      limitations and new challenges.
AB  - Biological psychiatry has made significant advances through the development of
      postmortem studies, animal models, and studies with living humans. Although these
      approaches each have advantages and disadvantages, the postmortem field is
      undergoing a significant shift toward more complex and informative methodologies.
      In the first part of this review, we summarize the long-standing methodologic
      challenges facing this field. In the second part of the article, we discuss the
      innovative approaches being used for postmortem studies, including laser capture
      microdissection and subcellular fractionization. These techniques will permit
      scientists working in the postmortem field to ask and answer the largest possible
      questions, providing new targets for drug discovery and improved treatments for
      severe mental illness.

PMID- 21094489
TI  - Isolation and characterization of cellulose nanofibrils from wheat straw using
      steam explosion coupled with high shear homogenization.
AB  - Cellulose nanofibrils of diameter 10-50nm were obtained from wheat straw using
      alkali steam explosion coupled with high shear homogenization. High shear results
      in shearing of the fiber agglomerates resulting in uniformly dispersed
      nanofibrils. The chemical composition of fibers at different stages were analyzed
      according to the ASTM standards and showed increase in alpha-cellulose content
      and decrease in lignin and hemicellulose. Structural analysis of steam exploded
      fibers was carried out by Fourier Transform Infrared (FT-IR) spectroscopy and X
      ray diffraction (XRD). Thermal stability was higher for cellulose nanofibrils as
      compared to wheat straw and chemically treated fibers. The fiber diameter
      distribution was obtained using image analysis software. Characterization of the
      fibers by AFM, TEM, and SEM showed that fiber diameter decreases with treatment
      and final nanofibril size was 10-15nm. FT-IR, XRD, and TGA studies confirmed the
      removal of hemicellulose and lignin during the chemical treatment process.

PMID- 21094491
TI  - The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled
      haemorrhagic shock in swine.
AB  - BACKGROUND: Development of Haemoglobin-based oxygen carriers (HBOCs) as blood
      substitutes has reached an impasse due to clinically adverse outcomes attributed
      to vasoconstriction secondary to nitric oxide (NO) scavenging. Studies suggest
      haemoglobin exhibits nitrite reductase activity that generates NO and N(2)O(3);
      harnessing this property may offset NO scavenging. Therefore, the effects of
      concomitantly infusing sodium nitrite (NaNO(2)) with HBOC-201 were investigated.
      METHODS: Swine underwent uncontrolled liver haemorrhage before receiving up to
      three 10min 10ml/kg infusions of HBOC-201 (HBOC) with or without concurrent
      NaNO(2) (5.4MUmol/kg [LD NaNO(2)] or 10.8MUmol/kg [HD NaNO(2)]) or 6% Hetastarch
      (HEX) with or without HD NaNO(2) during "prehospital" resuscitation (15, 30 and
      45min after injury). Definitive surgical care occurred at 75min; anaesthetic
      recovery at 120min. Animals were euthanised at 72h. RESULTS: NaNO(2) temporarily
      reduced systemic and pulmonary blood pressure increases from HBOC in a dose
      dependent fashion. There was no significant effect between groups in indices of
      tissue oxygenation or survival. Adverse clinical signs requiring humane
      euthanasia occurred with highest frequency after HBOC+HD NaNO(2) (3 of 4 pigs)
      and HBOC+LD NaNO(2) (2 of 4 pigs). Gross evidence of pulmonary congestion was
      observed in 5 of 8 swine receiving a HBOC and NaNO(2) combination compared to 1
      of 16 swine receiving HBOC alone, HEX alone, or HEX+NaNO(2). Gross lesions
      correlated with histological evidence of pulmonary oedema and congestion, and in
      2 of 4 HBOC+HD NaNO(2) pigs, pulmonary fibrin thrombi also were found. No other
      pig had similar evidence of thrombi. Asymmetric pre-resuscitation cardiac index
      was a potential confounder. CONCLUSIONS: A significant interaction between
      NaNO(2) and HBOC-201 ameliorated HBOC-201 vasoconstrictive effects, consistent
      with HBOC possessing a nitrite reductase activity that generates vasodilator NO
      equivalents. Results were relatively equivalent in survival and markers of tissue
      oxygenation. The highest dose of NaNO(2) was the most effective in reducing HBOC
      associated pulmonary and systemic vasoactivity but also with the highest
      incidence of adverse events. In this model, the transient nature of NaNO(2) in
      off-setting HBOC-201 vasoconstriction makes it less clinically promising than
      anticipated and the combination of NaNO(2) and HBOC appear to increase the risk
      of pulmonary complications in a dose-dependent fashion independently of
      haemodilutional effects on haemostatic components.

PMID- 21094490
TI  - Intrauterine exposure to lead may enhance sensitization to common inhalant
      allergens in early childhood: a prospective prebirth cohort study.
AB  - BACKGROUND: Several in vivo and in vitro studies have shown that metal-rich
      particles may enhance allergic responses to house dust mites and induce an
      increased release of allergy-related cytokines. OBJECTIVES: The main goal of this
      analysis is to define the possible association of intrauterine exposure to lead
      and mercury with the occurrence of skin sensitization to common aeroallergens in
      early childhood. MATERIAL AND METHODS: The present study refers to a sample of
      224 women in the second trimester of pregnancy recruited from Krakow inner city
      area who had full term pregnancies and whose children underwent skin prick
      testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord
      blood and retested in children at age of 5 years. Aeroallergen concentrations in
      house dust were measured at the age of 3 years. The main health outcome (atopic
      status) was defined as the positive SPT to at least one common aeroallergen (Der
      f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis
      of the association between atopic status of children and exposure to metals, the
      study considered a set of covariates such as maternal characteristics (age,
      education, atopy), child's gender, number of older siblings, prenatal (measured
      via cord blood cotinine) and postnatal environmental tobacco smoke together with
      exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA
      adducts. RESULTS AND CONCLUSION: In the binary regression analysis, which
      controlled for the confounders, the risk ratio (RR) estimate for atopic
      sensitization was significantly associated with the lead exposure (RR=2.25,
      95%CI: 1.21-4.19). In conclusion, the data suggest that even very low-level of
      prenatal lead exposure may be implicated in enhancing sensitization to common
      aeroallergens in early childhood.

PMID- 21094492
TI  - Accelerated 18O-labeling in urinary proteomics.
AB  - Proteolytic (18)O-labeling of peptides has been studied and optimized in order to
      improve the labeling efficiency and to accelerate the process without increasing
      the degree of incomplete labeling. Using peptides generated from tryptic digested
      bovine serum albumin (BSA) and cytochrome c as model proteins, it was shown that
      complete labeling was achieved after 2 h at pH 6. To increase the sample
      throughput in a bottom-up proteomic setup, tryptic digestion of proteins in
      solution was replaced with tryptic digestion using immobilized trypsin. As a
      result, an integrated approach was made possible, where both digestion (pH 8) and
      (18)O/(16)O-labeling of the resulting peptides (pH 6) were done using immobilized
      trypsin beads. This simplified the sample handling and reduced the overall
      reaction time significantly: the setup enabled tryptic digestion and (18)O/(16)O
      labeling without sample transfer steps within 3.5 h with average (18)O/(16)O
      ratios of 0.96+/-0.13 in aqueous buffer. The initial results were confirmed with
      a more complex matrix, by spiking urine with the model proteins, yielding results
      comparable with the ratios obtained in buffer. Satisfying ratios were also
      achieved regarding urinary proteins identified in a full scale bottom-up
      experiment. Average (18)O/(16)O-peptide ratios of 0.83+/-0.13 and 0.91+/-0.27
      indicated good performance in a highly relevant matrix for biomarker discovery.

PMID- 21094493
TI  - Folate-functionalized nanoparticles for controlled 5-Fluorouracil delivery.
AB  - In this paper, folate conjugated poly(epsilon-caprolactone-co-4-maleate-epsilon
      caprolactone) (P(CL-co-MCL)-folate) was prepared by a carbodiimide coupling
      reaction, i.e., the vitamin folic acid (FA) was covalently linked to the main
      chain of the maleate-functionalized polymer, poly(epsilon-caprolactone-co-4
      maleate-epsilon-caprolactone) (P(CL-co-MCL)). Then the 5-Fluorouracil (5-FU)
      loaded nanoparticles of P(CL-co-MCL)-folate were achieved by solvent-evaporation
      method. Their properties were extensively studied by dynamic light scattering
      (DLS) and scan electron microscopy (SEM). DLS and SEM showed that the
      nanoparticles were in a well-defined spherical shape with a uniform size
      distribution. We also investigated the entrapment and in vitro release behavior,
      which indicated that the release speed of 5-FU could be well controlled and the
      release half-life period could reach 16.86h, which was 26.4 times longer than
      that of pure 5-FU. The in vitro targeting test displayed that the 5-FU loaded
      P(CL-co-MCL)-folate nanoparticles exhibited an enhanced cell inhibition because
      folate targeting increased the concentration of 5-FU loaded P(CL-co-MCL)-folate
      nanoparticles in the tumor cells with folate receptor overexpressed. Meanwhile,
      the tumor inhibition of 5-FU loaded P(CL-co-MCL)-folate nanoparticles was much
      higher than that of pure 5-FU and that of 5-FU loaded P(CL-co-MCL) nanoparticles.
      Therefore, P(CL-co-MCL)-folate nanoparticles would be highly beneficial for
      biomedical and pharmaceutical applications.

PMID- 21094494
TI  - Landau-Levich menisci.
AB  - As shown by Landau, Levich and Derjaguin, a plate withdrawn out of a wetting bath
      at low capillary numbers deforms the very top of the liquid reservoir. At this
      place, a dynamic meniscus forms, whose shape and curvature select the thickness
      of the film entrained by the plate. In this paper, we measure accurately the
      thickness of the entrained film by reflectometry, and characterize the dynamic
      meniscus, which is found to decay exponentially towards the film. We show how
      this shape is modified when reversing the motion: as a plate penetrates the bath,
      the dynamic meniscus can "buckle" and present a stationary wavy profile, which we
      discuss.

PMID- 21094495
TI  - Novel cationic 6-lauroxyhexyl lysinate modified poly(lactic acid)-poly(ethylene
      glycol) nanoparticles enhance gene transfection.
AB  - The leading principle of non-viral delivery systems for gene therapy is to
      mediate high levels of gene expression with low cytotoxicity. Nowadays,
      biodegradable nanoparticles formulated with poly(lactic acid)-poly(ethylene
      glycol) (PLA-PEG) were wildly developed. However, the relative lower gene
      transfection efficiency and higher cytotoxicity still remained critical problems.
      To address these limitations, PLA-PEG nanoparticles have been composited with
      other components in their formulation. Here, a novel cationic lipid, 6
      lauroxyhexyl lysinate (LHLN), was fabricated onto PLA-PEG nanoparticles as a
      charge modifier to improve the transfection efficiency and cytotoxicity. The
      obtained cationic LHLN modified PLA-PEG nanoparticles (LHLN-PLA-PEG NPs) could
      condense pDNA thoroughly via electrostatic force, leading to the formation of the
      LHLN-PLA-PEG NPs/pDNA complexes (NPs/DNA complexes). The nanoparticles obtained
      have been characterized in relation to their physicochemical and biological
      properties, and the results are extremely promising in terms of low cell toxicity
      and high transfection efficiency. These results indicated that the novel cationic
      LHLN modified PLA-PEG nanoparticles could enhance gene transfection in vitro and
      hold the potential to be a promising non-viral nanodevice.

PMID- 21094496
TI  - Stroke risk and prognostic factors of asymptomatic middle cerebral artery
      atherosclerotic stenosis.
AB  - BACKGROUND AND PURPOSE: Stroke risk of asymptomatic atherosclerotic middle
      cerebral artery (MCA) stenosis has not been well studied. This study was designed
      to investigate stroke risk and prognostic factors of asymptomatic atherosclerotic
      MCA stenosis. MATERIALS AND METHODS: A total of 200 consecutive patients who
      visited the transcranial Doppler ultrasound (TCD) laboratory of our hospital and
      who met the following criteria were prospectively enrolled in this study:
      diagnosed as MCA stenosis due to atherosclerosis by TCD, age above 40 years old,
      no history of ischemic stroke or transient ischemic attack (TIA), no ipsilateral
      carotid artery stenosis. The mean follow-up time was 38.3 +/- 9.9 (range 4 to 60)
      months. RESULTS: Thirteen patients were lost to follow up. Seven patients (3.8%)
      developed ischemic stroke or TIA during the follow-up period, with an occurrence
      rate of 0.5% in the first year and 1.6% in the second year. Three were in the
      blood supply region of diseased vessels, three were in the contralateral
      hemisphere and one case of TIA occurred in the posterior circulation. Univariate
      analysis showed that diabetes mellitus (DM) (X2=9.168, p=0.002) and carotid
      atherosclerotic plaque (X2=4.403, p=0.036) were associated with higher risk of
      stroke occurrence in this cohort. CONCLUSIONS: The stroke risk in patients with
      asymptomatic atherosclerotic MCA stenosis was low and remained stable during
      follow up. Higher risk of stroke occurrence is associated with DM and carotid
      atherosclerotic plaque.

PMID- 21094497
TI  - Brain natriuretic peptide is a marker associated with thrombus in stroke patients
      with atrial fibrillation.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) and atrial thrombus are at
      high risk of thromboembolic events. We investigated whether BNP levels can serve
      as a biological marker of thrombus. METHODS: We prospectively enrolled patients
      with AF within 7days of an ischemic stroke and transient ischemic attack (TIA).
      We measured BNP levels in all patients while they underwent transesophageal
      echocardiography (TEE) and then assigned them to groups based on the presence
      (positive group) or absence (negative group) of left atrial thrombus. Factors
      associated with atrial thrombus were investigated using multivariate logistic
      regression analysis. RESULTS: Of the 67 (male, n = 40; mean age, 76.5 +/- 11.1
      years) enrolled patients, 17 (25.4%) had left atrial thrombus. The incidence of
      hypertension was significantly higher in the positive, than in the negative group
      (88.2% vs. 58.0%, p = 0.020). The BNP level was also significantly higher in the
      positive, than in the negative group (median (interquartile range) 189.8 (141.4
      473.2) vs. 117.9 (70.3-187.1) pg/ml, p=0.012). The optimal cut-off value,
      sensitivity, and specificity of BNP levels to distinguish the positive, from the
      negative group were 140.0 pg/ml, 76.5%, and 62.0%, respectively. Multivariate
      logistic regression analysis demonstrated that a BNP concentration of>140.0 pg/ml
      (odds ratio, 5.62; 95% CI, 1.39-22.66, p = 0.015) was an independent factor
      associated with thrombus. CONCLUSION: Levels of BNP can serve as a marker of left
      atrial thrombus in acute ischemic stroke and TIA in patients with AF.

PMID- 21094498
TI  - Cold blood spinoplegia under motor-evoked potential monitoring during thoracic
      aortic surgery.
AB  - OBJECTIVE: Motor-evoked potential monitoring is used to prevent paraplegia during
      thoracic aortic surgery. Multidetector computed tomography has been used
      preoperatively to detect the Adamkiewicz artery, but the hemodynamic significance
      of the Adamkiewicz artery is controversial. This study aims to evaluate whether
      the multidetector computed tomography-defined Adamkiewicz artery is
      hemodynamically essential and needs to be reconstructed with cold blood
      spinoplegia under motor-evoked potential monitoring. METHODS: From 2005 to 2008,
      both preoperative multidetector computed tomographic analysis and intraoperative
      neurogenic motor-evoked potential monitoring with cold blood infusion into the
      clamped segment of the aorta were done in 15 patients. A motor-evoked potential
      decrease to less than 50% of the initial value at 3 minutes after cold blood
      infusion determined the hemodynamic significance of the multidetector computed
      tomography-defined Adamkiewicz artery. Adamkiewicz arteries determined to be
      essential were reconstructed, and those determined to be nonessential were
      sacrificed. RESULTS: The Adamkiewicz artery was involved in the clamped segment
      of the aorta in 11 cases. After cold blood infusion, 8 patients experienced no
      significant motor-evoked potential decrease, and Adamkiewicz artery ligation was
      undertaken, whereas a moderate motor-evoked potential decrease was noted in 1
      patient, prompting reconstruction. None of these 9 patients had permanent
      neurologic deficits. In 2 patients, the Adamkiewicz artery was reconstructed
      based on motor-evoked potential findings, with paraparesis occurring in 1
      patient. In 4 patients without Adamkiewicz artery involvement in the clamped
      segment, there was no neurologic deficit. CONCLUSIONS: Cold blood infusion
      accelerates motor-evoked potential changes and might enable decision making
      regarding the need for reconstruction of multidetector computed tomography
      defined Adamkiewicz arteries. Cold blood-loaded motor-evoked potential is
      beneficial to minimize Adamkiewicz artery reconstruction time and limit spinal
      cord ischemia.

PMID- 21094499
TI  - Surveillance and epidemiology of surgical site infections after cardiothoracic
      surgery in The Netherlands, 2002-2007.
AB  - OBJECTIVE: Surgical site infections after cardiothoracic surgery substantially
      increase the risk for illness, mortality, and costs. Surveillance of surgical
      site infections might assist in the prevention of these infections. This study
      describes the Dutch surveillance methods and results of data collected between
      2002 and 2007. METHODS: Three cardiothoracic procedures were included: coronary
      artery bypass graft procedures, valve surgery, and a combination of coronary
      artery bypass graft procedures with concomitant valve surgery. The surgical site
      infections were divided into sternal and harvest-site infections. Postdischarge
      surveillance of surgical site infections was mandatory for sternal wounds and
      elective for harvest-site wounds, with a follow-up period of 42 postoperative
      days. Multivariate logistic regression was used for risk factor analysis of
      coronary artery bypass grafts, with adjustment for random variation among
      hospitals. RESULTS: Eight of the 16 Dutch cardiothoracic centers participated and
      collected data on 4066 procedures and 183 surgical site infections, revealing a
      surgical site infection rate of 2.4% for sternal wounds and 3.2% for harvest
      sites. Sixty-one percent of all surgical site infections were recorded after
      discharge. For sternal surgical site infections after coronary artery bypass
      graft procedures, the significant risk factors were rethoracotomy, diabetes,
      preoperative length of stay, and obesity; for harvest-site infections, the most
      relevant risk factor was a long time on extracorporeal circulation. Adjusted
      surgical site infection rates regarding coronary artery bypass graft procedures
      varied between hospitals from 0.0% to 9.7%. CONCLUSIONS: Large differences were
      found in surgical site infection rates between Dutch hospitals, which indicate
      room for improvement. The follow-up of patients after hospital discharge reduces
      underestimation of surgical site infection rates.

PMID- 21094501
TI  - Fast and easy method for seagrass monitoring: application of acoustic telemetry
      to precision mapping of Posidonia oceanica beds.
AB  - Posidonia oceanica is an endemic seagrass from the Mediterranean Sea. It is an
      indicator of water quality and of the ecological state of coastal ecosystems. The
      aim of this paper is to test acoustic telemetry for monitoring the position of P.
      oceanica meadow limits with varied types. After evaluating the accuracy of the
      system, we present results from a spatiotemporal survey of P. oceanica meadows on
      nine sites located on the French coast. The method has been demonstrated to be
      highly efficient for high precision underwater mapping regardless of meadow type,
      with 1 cm accuracy for a distance of 40 m between the base and the pointer. A
      temporal survey led at Cerbere-Banyuls shows a weak global progression of 4 m2
      (progression of 26 m2 - regression of 22 m2) between 2006 and 2010. Finally, we
      discuss the cost and efficiency of this method, and wether it should be
      generalized for further studies.

PMID- 21094500
TI  - Pretreatment with angiotensin-converting enzyme inhibitor improves doxorubicin
      induced cardiomyopathy via preservation of mitochondrial function.
AB  - OBJECTIVE: Doxorubicin is a widely used chemotherapy drug, but its application is
      associated with cardiotoxicity. Free radical generation and mitochondrial
      dysfunction are thought to contribute to doxorubicin-induced cardiac failure.
      Angiotensin-converting enzyme inhibitors are commonly used as cardioprotective
      agents and have recently been shown in clinical studies to be efficacious in the
      prevention of anthracycline-induced heart failure. This study evaluated a
      mechanism for these protective effects by testing the ability of the angiotensin
      converting enzyme inhibitor enalapril to preserve mitochondrial function in a
      model of chronic doxorubicin treatment in rats. METHODS: Sprague Dawley rats were
      divided into 3 groups and followed for a total of 10 weeks: (1) control
      untreated, (2) doxorubicin treated, and (3) doxorubicin + enalapril treated.
      Doxorubicin was administered via intraperitoneal injection at weekly intervals
      from weeks 2 to 7. Enalapril was administered in the drinking water of the
      doxorubicin + enalapril group for the study duration. RESULTS: Doxorubicin
      treatment produced a significant loss in left ventricular contractility (P <
      .05), decrease in mitochondrial function via impairment of state-3 respiration,
      decrease in the cytosolic fraction of adenosine triphosphate, and up-regulation
      of free radical production. Enalapril significantly attenuated the decrease in
      percent fractional shortening (P < .05) and prevented the doxorubicin-associated
      reduction in respiratory efficiency and cytosolic adenosine triphosphate content
      (P < .05). Enalapril also abolished the robust doxorubicin-induced increase in
      free radical formation. CONCLUSIONS: Administration of enalapril attenuates
      doxorubicin-induced cardiac dysfunction via preservation of mitochondrial
      respiratory efficiency and reduction in doxorubicin-associated free radical
      generation.

PMID- 21094502
TI  - The most temperature-adapted corals have an Achilles' Heel.
AB  - The corals of the Persian/Arabian Gulf are better adapted to temperature
      fluctuations than elsewhere in the Indo-Pacific. The Gulf is an extreme marine
      environment displaying the highest known summer water temperatures for any reef
      area. The small and shallow sea can be considered a good analogue to future
      conditions for the rest of the world's oceans under global warming. The fact that
      corals can persist in such a demanding environment indicates that they have been
      able to acclimatize and selectively adapt to elevated temperature. The
      implication being that colonies elsewhere may be able to follow suit. This in
      turn provides hope that corals may, given sufficient time, similarly adapt to
      survive even in an impoverished form, under conditions of acidification-driven
      lowering of CaCO3 saturation state, a further consequence of raised atmospheric
      CO2. This paper demonstrates, however, that the uniquely adapted corals of the
      Gulf may, within the next three centuries, be threatened by a chronic habitat
      shortage brought about by the dissolution of the lithified seabed on which they
      rely for colonisation. This will occur due to modifications in the chemical
      composition of the Gulf waters due to climate change.

PMID- 21094503
TI  - Steroidal saponins from Yucca gloriosa L. rhizomes: LC-MS profiling, isolation
      and quantitative determination.
AB  - The occurrence of steroidal saponins in the rhizomes of Yucca gloriosa has been
      detected by LC-MS. On the basis of the LC-MS analysis, five steroidal glycosides,
      including three spirostane, one furostane and one cholestane glycosides, along
      with seven known compounds have been isolated and characterized by ESI-MS and by
      the extensive use of 1D- and 2D-NMR experiments. Quantitative analysis of the
      steroidal glycosides in Y. gloriosa rhizomes was performed by an LC-MS method
      validated according to European Medicines Agency (EMEA) guidelines. The dried
      BuOH extract obtained from rhizomes contains more than 25% w/w of glycosides,
      thus Y. gloriosa rhizomes can be considered a rich source of steroidal
      glycosides.

PMID- 21094504
TI  - Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii
      Hook.f.).
AB  - Tripterygium wilfordii Hook.f., known as Leigongteng (Thunder God Vine) in
      traditional Chinese medicine, has attracted much attention for its applications
      in relieving autoimmune disorders such as rheumatoid arthritis and systemic lupus
      erythematosus, and for treating cancer. Molecular analyses of the ITS and 5S rDNA
      sequences indicate that T. hypoglaucum and T. doianum are not distinct from T.
      wilfordii, while T. regelii should be recognized as a separate species. The
      results also demonstrate potential value of rDNA sequence data in forensic
      detection of adulterants derived from Celastrus angulatus in commercial samples
      of Leigongteng.

PMID- 21094505
TI  - Fatal bovine anaplasmosis in a herd with new genotypes of Anaplasma marginale,
      Anaplasma ovis and concurrent haemoplasmosis.
AB  - Haematological and molecular analysis of blood samples was carried out during an
      outbreak of bovine anaplasmosis in Hungary. Acute disease was observed in five
      animals, two of which died. Anaplasma-carrier state was diagnosed in 69 (92%) of
      cattle. Further evaluation of 24 blood samples revealed concurrent infections
      with Mycoplasma wenyonii and 'CandidatusM. haemobos' in 22 and 21 animals,
      respectively. In addition, two cows were identified with rickettsaemia. Regarding
      molecular investigation of potential hard tick vectors, Haemaphysalis inermis and
      Dermacentor marginatus males collected from the animals were PCR-negative.
      However, in one pool (out of 18) of Ixodesricinus males, and in six pools (out of
      18) of D. reticulatus males the msp4 gene of Anaplasma marginale was detected. In
      the same I. ricinus pool Anaplasma ovis was also identified. All ticks were
      negative for haemoplasmas. Anaplasma sequences yielded 97-99% homology to
      sequences deposited in the Genbank. This is the first report of fatal bovine
      anaplasmosis associated with divergent A. marginale genotypes and concurrent
      'CandidatusM. haemobos' infection, as well as of an A. ovis strain in ticks
      collected from cattle.

PMID- 21094506
TI  - Characterization of Bunostomum trigonocephalum and Bunostomum phlebotomum from
      sheep and cattle by internal transcribed spacers of nuclear ribosomal DNA.
AB  - In the present study, samples representing Bunostomum trigonocephalum and
      Bunostomum phlebotomum from sheep and cattle in Heilongjiang Province, China,
      were characterized and grouped genetically by the first (ITS-1) and second (ITS
      2) internal transcribed spacers (ITS) of nuclear ribosomal DNA (rDNA). The rDNA
      region including the ITS-1, 5.8S, ITS-2, and flanking 18S and 28S rDNA sequences
      was amplified by polymerase chain reaction (PCR), then sequenced and compared
      with that of other members of the hookworms available in GenBankTM, and
      phylogenetic relationships between them were reconstructed using the Maximum
      Parsimony method. The ITS-1, 5.8S, and ITS-2 sequences of the sheep hookworm were
      381, 153, and 231bp in length, respectively, and the corresponding sequences of
      the cattle hookworm were 392, 153, and 240bp in length. The identity of ITS
      sequences of B. trigonocephalum and B. phlebotomum from sheep and cattle was
      87.4%. A PCR-linked restriction fragment length polymorphism (PCR-RFLP) assay
      using restriction endonuclease Nde I was established for the unequivocal
      differentiation of the two hookworm species. Phylogenetic analyses based on the
      ITS sequences revealed that B. trigonocephalum and B. phlebotomum were closely
      related, but they represent two different species.

PMID- 21094507
TI  - Risk factors for death and unwanted early slaughter in Swiss veal calves kept at
      a specific animal welfare standard.
AB  - Calf losses (CL, mortality and unwanted early slaughter) in veal production are
      of great economic importance and an indicator of welfare. The objective of the
      present study was to evaluate CL and the causes of death on farms with a specific
      animal welfare standard (SAW) which exceeds the Swiss statutory regulations. Risk
      factors for CL were identified based on information about management, housing,
      feeding, and medication. In total, 74 production cohorts (2783 calves) of 15
      farms were investigated. CL was 3.6%, the main causes of death were digestive
      disorders (52%), followed by respiratory diseases (28%). Factors significantly
      associated with an increased risk for CL were a higher number of individual daily
      doses of antibiotics (DDA), insufficient wind deflection in winter, and male
      gender. For administration of antibiotics to all calves of the cohort, a DDA of
      14-21 was associated with a decreased risk for CL compared to a DDA of 7-13 days.

PMID- 21094508
TI  - Determination of flagellar types by PCR-RFLP analysis of enteropathogenic
      Escherichia coli (EPEC) and Shiga toxin-producing E. coli (STEC) strains isolated
      from animals in Sao Paulo, Brazil.
AB  - This study evaluated the polymerase chain reaction- restriction fragment length
      polymorphism (PCR-RFLP) analysis of fliC for typing flagella antigen (H) of Shiga
      toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC)
      strains isolated from different animals. The molecular typing of the H type was
      efficient in the determination of 93 (85%) strains. Two nonmotile (H-) E. coli
      strains showed a PCR-RFLP electrophoretic profile that did not match known H type
      patterns. The fliC nucleotide sequence of strains B2N and 4a revealed a
      nucleotide substitution at the restriction site and a nucleotide insertion that
      generated a stop codon, respectively. The results of this study showed that PCR
      RFLP analysis of fliC is faster, less laborious and as efficient for the
      determination of H type E. coli isolated from animals, compared to serotyping and
      that it is useful in determining H type in nonmotile strains and strains
      expressing non-reactive H antigens. Moreover, the fliC sequence of strain B2N
      suggests that we could have found a new flagellin antigen type.

PMID- 21094509
TI  - In vitro properties of small ruminant lentivirus genotype E.
AB  - Small ruminant lentivirus genotype E lacks the dUTPase subunit and vpr-like gene.
      Two strains (Roccaverano and Seui) with identical genetic organization have been
      described, with the env HV1-HV2 domains being the most divergent. Although
      dUTPase and vpr-like deletions have been involved in the RT fidelity in non
      dividing cells, both strains were able to replicate efficiently in blood derived
      macrophages (BDM), while virus production of E1 subtype was reduced or abrogated
      in replicating fibroblastic-like cells. The transcriptional activity of genotype
      E was similar in these two cellular populations. When viral pseudotypes were
      generated with the env of both viruses, Roccaverano pseudotype displayed a
      paranuclear localization on BDM, suggesting a different mechanism of entry.
      Polymorphic GAS and TAS sites in the U3 region, further suggest that a population
      different from classically activated macrophages can be infected by these
      viruses, opening new insights into lentiviruses with low or null pathogenic
      potential.

PMID- 21094511
TI  - A proviral derivative from a reference attenuated EIAV vaccine strain failed to
      elicit protective immunity.
AB  - To investigate essential factors that determine the efficacy of vaccines against
      lentiviruses, an effective attenuated equine infectious anemia virus (EIAV)
      vaccine strain and a proviral derivative of the vaccine were compared with
      respect to differences in inducing protective immunity. Although these two
      strains replicated equally well in vitro and in vivo, the proviral strain induced
      significantly less protection from disease and infection caused by viral
      challenge and significantly lower specific neutralizing capability. These
      findings indicated that the proviral strain had lost the ability to stimulate
      immune protection compared to the parental vaccine strain. A further analysis of
      the envelope gp90 gene variation revealed that compared to the proviral strain,
      the vaccine strain displayed a wide sequence diversity in immunogen composition.
      Thus, we inferred that the differences in immunogen composition might be the
      major cause for the failure of the proviral derivative to elicit the immune
      protection induced by the parental strain.

PMID- 21094510
TI  - Guinea pig cytomegalovirus GP84 is a functional homolog of the human
      cytomegalovirus (HCMV) UL84 gene that can complement for the loss of UL84 in a
      chimeric HCMV.
AB  - The guinea pig cytomegalovirus (GPCMV) co-linear gene and potential functional
      homolog of HCMV UL84 (GP84) was investigated. The GP84 gene had delayed early
      transcription kinetics and transient expression studies of GP84 protein (pGP84)
      demonstrated that it targeted the nucleus and co-localized with the viral DNA
      polymerase accessory protein as described for HCMV pUL84. Additionally, pGP84
      exhibited a transdominant inhibitory effect on viral growth as described for
      HCMV. The inhibitory domain could be localized to a minimal peptide sequence of
      99 aa. Knockout of GP84 generated virus with greatly impaired growth kinetics.
      Lastly, the GP84 ORF was capable of complementing for the loss of the UL84 coding
      sequence in a chimeric HCMV. Based on this research and previous studies we
      conclude that GPCMV is similar to HCMV by encoding single copy co-linear
      functional homologs of HCMV UL82 (pp71), UL83 (pp65) and UL84 genes.

PMID- 21094512
TI  - Analysis of PCDD/Fs and dioxin-like PCBs in atmospheric deposition samples from
      the Flemish measurement network: Optimization and validation of a new CALUX
      bioassay method.
AB  - Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a
      fast, sensitive and inexpensive tool for the analysis of a high number of
      samples, validation of new methods is urgently needed. In this study, a new
      method for the analysis of PCDD/Fs and dioxin-like PCBs in atmospheric deposition
      samples with the CALUX bioassay was developed, optimized and validated. The
      method consists of 4 steps: filtration, extraction, clean up and bioassay
      analysis. To avoid the use of large amounts of toxic solvents, new techniques
      were used for filtration and extraction: a C18 filter was used instead of a
      liquid/liquid extraction and an Accelerated Solvent Extractor (ASE) was used
      instead of the traditional soxhlet extraction. After pre-oxidation of the sample
      extract, clean up was done using a multi-layer silica gel column coupled to a
      carbon column. The PCDD/F and PCB fractions were finally analyzed with the
      H1L7.5c1 and/or the H1L6.1c3 mouse hepatoma cell lines. The limit of
      quantification was 1.4pg CALUX-BEQm(-2)d(-1) for the PCBs and 5.6pgCALUX-BEQm(
      2)d(-1) for the PCDD/Fs, when using the new sensitive H1L7.5c1 cell line. The GC
      HRMS recovery for all PCDD/F congeners was between 55% and 112%, with a mean
      recovery of 90%. CALUX recoveries of spiked procedural blanks were between the
      accepted ranges of 80-120%. Repeatability and reproducibility were satisfactory
      and no interferences from metals were detected. The first results from the
      Flemish measurement program showed good correlation between CALUX and GC-HRMS.

PMID- 21094513
TI  - Levels of 210Po and 210Pb in fish and molluscs in Slovenia and the related dose
      assessment to the population.
AB  - 210Po and 210Pb activity concentrations in fish from the Slovenian part of
      Adriatic Sea, in the vicinity of a former uranium mine at Zirovski vrh and from
      the Slovenian market were determined. In addition, 210Po and 210Pb activity
      concentrations in squid from the Slovenian market and in mussels from the
      Slovenian part of the Adriatic Sea were also determined. Fish, squid and mussel
      consumption in Slovenia was assessed from the data available from Eurostat and
      Food and Agriculture Organisation (FAO) and the data used for the corresponding
      dose calculation. Fish species with the highest activity concentrations were
      grilled to assess possible loss of 210Po during the food preparation process.
      Samples were freeze dried and radiochemical separation of 210Po and 210Pb was
      performed. Measurements of 210Po were performed by alpha spectrometry and 210Pb
      by a low background gas-flow proportional counter. 210Po activity concentrations
      in fish, squid and mussels were from 0.039 to 35.0 Bqkg-1 fresh weight and 210Pb
      activity concentrations were from 0.08 to 3.03 Bqkg-1 fresh weight. Grilling of
      fish resulted in no significant loss of 210Po at 90 degrees C. The assessed
      combined annual effective ingestion dose due to 210Po and 210Pb for fish, squid
      and mussels consumed in Slovenia is 47.6 MUSv year-1.

PMID- 21094514
TI  - Assessing the impact of waterborne and dietborne cadmium toxicity on
      susceptibility risk for rainbow trout.
AB  - The purpose of this study was to use a risk-based integrated-scale toxicological
      model to examine the impact of waterborne and dietborne cadmium (Cd) toxicity on
      rainbow trout (Oncorhynchus mykiss) susceptibility appraised with recent
      published data. A probabilistic assessment model was performed to estimate Cd
      susceptibility risk. The dose-response models were constructed based on two
      endpoints of % Cd in metabolically active pool (MAP) and susceptibility time that
      causes 50% effect (ST50). We further constructed an elimination-detoxification
      recovery scheme to enhance the model predictive ability. We found a 95%
      probability of % Cd in gill and liver MAP exceeding 47-49% and it was likely (70%
      probability) to have exceeded 52-55%, but it was unlikely (30% probability) to
      have exceeded 56-60%. In contrast to gill and liver, gut had a relative lower Cd
      susceptibility risk (15-17% Cd in MAP) with a longer ST50. We suggested that the
      proposed probabilistic risk assessment framework can incorporate the elimination
      detoxification-recovery scheme to help government based biomonitoring and
      bioassessment programs to prevent potential aquatic ecosystems and human health
      consequences.

PMID- 21094515
TI  - Assessing land-use effects on water quality, in-stream habitat, riparian
      ecosystems and biodiversity in Patagonian northwest streams.
AB  - Changes in land-use practices have affected the integrity and quality of water
      resources worldwide. In Patagonia there is a strong concern about the ecological
      status of surface waters because these changes are rapidly occurring in the
      region. To test the hypothesis that greater intensity of land-use will have
      negative effects on water quality, stream habitat and biodiversity we assessed
      benthic macroinvertebrates, riparian/littoral invertebrates, fish and birds from
      the riparian corridor and environmental variables of 15 rivers (Patagonia)
      subjected to a gradient of land-use practices (non-managed native forest, managed
      native forest, pine plantations, pasture, urbanization). A total of 158
      macroinvertebrate taxa, 105 riparian/littoral invertebrate taxa, 5 fish species,
      34 bird species, and 15 aquatic plant species, were recorded considering all
      sites. Urban land-use produced the most significant changes in streams including
      physical features, conductivity, nutrients, habitat condition, riparian quality
      and invertebrate metrics. Pasture and managed native forest sites appeared in an
      intermediate situation. The highest values of fish and bird abundance and
      diversity were observed at disturbed sites; this might be explained by the
      opportunistic behavior displayed by these communities which let them take
      advantage of increased trophic resources in these environments. As expected, non
      managed native forest sites showed the highest integrity of ecological conditions
      and also great biodiversity of benthic communities. Macroinvertebrate metrics
      that reflected good water quality were positively related to forest land cover
      and negatively related to urban and pasture land cover. However, by offering
      stream edge areas, pasture sites still supported rich communities of
      riparian/littoral invertebrates, increasing overall biodiversity.
      Macroinvertebrates were good indicators of land-use impact and water quality
      conditions and resulted useful tools to early alert of disturbances in streams.
      Fish and birds having a greater ability of dispersion and capacity to move
      quickly from disturbances would reflect changes at a higher scale.

PMID- 21094516
TI  - Comparison of mercury and zinc profiles in peat and lake sediment archives with
      historical changes in emissions from the Flin Flon metal smelter, Manitoba,
      Canada.
AB  - The copper-zinc smelter at Flin Flon, Manitoba, was historically the largest
      single Hg point-source in Canada, as well as a major source of Zn. Although
      emissions were reported by industry to have declined significantly since the late
      1980s, these reductions have never been independently verified. Here, the
      histories of Hg and Zn deposition over the past century or more were determined
      at five lake sediment and three peat study sites in the surrounding region. At
      sites spanning the range from heavy to minor pollution, lake sediment Hg and Zn
      concentration and flux profiles increased significantly in the early 1930s after
      the smelter opened. Two of the three peat archives were wholly or partially
      compromised by either physical disturbances or biogeochemical transitions which
      reduced their effectiveness as atmospheric metal deposition recorders. But the
      remaining peat records, including a detailed recent 20 yr record at a moderately
      polluted site, appeared to show that substantive reductions in metal levels had
      occurred after the late 1980s, coincident with the reported emission reductions.
      However, the lake sediment results, taken at face value, contradicted the peat
      results in that no major declines in metal concentrations or fluxes occurred over
      recent decades. Mercury and Zn fluxes have in fact increased substantially since
      1988 in most lakes. We suggest that this discrepancy may be explained by
      catchment soil saturation by historically deposited metals which are now
      mobilizing and leaching into lakes, as has been reported from other smelter
      polluted systems in Canada, whereas the upper sections of the peat cores
      reflected recent declines in atmospheric deposition. However, further research
      including instrumented wet and dry deposition measurements and catchment/lake
      mass balance studies is recommended to test this hypothesis, and to provide
      definitive data on current atmospheric metal deposition rates in the area.

PMID- 21094517
TI  - Disease-modifying effect and economic implications of sublingual immunotherapy.

PMID- 21094518
TI  - Future forms of immunotherapy.
AB  - Allergic respiratory diseases affect approximately 15% of the US population.
      Allergen immunotherapy has been a treatment option for diseases such as allergic
      rhinitis, allergic asthma, and venom allergy for the last 100 years. During the
      first 75 years, conventional subcutaneous immunotherapy did not change much.
      However, the last 25 years has seen substantial growth in the development of
      alternatives to conventional subcutaneous immunotherapy. The addition of
      omalizumab, an anti-IgE mAb, to immunotherapy offers the potential for increased
      safety and efficacy. Activation of the innate immune system through Toll-like
      receptor agonists with and without specific allergens appears to improve the
      immunologic responses and clinical outcomes in patients with allergic diseases.
      The use of chemically altered allergens, allergoids, recombinant allergens, and
      relevant T-cell epitope peptides are all approaches that have yielded positive
      results. Finally, alternative modes of delivery hold promise, with sublingual
      immunotherapy rapidly approaching mainstream use in many countries. One thing is
      clear: the next century of immunotherapy will be vastly different from today's
      current standard of care.

PMID- 21094520
TI  - Higher-ovalbumin-content influenza vaccines are well tolerated in children with
      egg allergy.

PMID- 21094519
TI  - Polymorphous lymphoproliferative disorder with Hodgkin-like features in common
      gamma-chain-deficient severe combined immunodeficiency.

PMID- 21094521
TI  - A genome-wide association study to identify genetic determinants of atopy in
      subjects from the United Kingdom.
AB  - BACKGROUND: A genetic component in the development of atopy has been identified.
      However, numerous heritability models have been proposed with inconsistent
      replication of susceptibility loci and genes. OBJECTIVE: We sought to use a
      genome-wide association study approach to examine genetic susceptibility to
      atopy, which was defined as increased specific IgE levels, positive skin prick
      test (SPT) responses, or both, within a large discovery cohort and 3 additional
      white populations. METHODS: Single nucleotide polymorphisms (SNPs) across the
      genome were tested for association with increased specific IgE levels (>= 0.35
      kU(A)/L) in the British 1958 Birth Cohort (1083 cases and 2770 control subjects;
      Illumina 550K Array) to 1 or more allergens, including house dust mite (Der p 1),
      mixed grass, or cat fur. Independent replication of identified loci (P <= .05)
      was assessed in 3 case-control cohorts from the United Kingdom (n = 3225).
      Combined analyses of data for top signals across cohorts were conducted for
      atopic phenotypes: increased specific IgE levels (1378 cases and 3151 control
      subjects) and positive SPT responses (1058 cases and 2167 control subjects).
      RESULTS: A single SNP on chromosome 13q14 met genome-wide significance (P = 2.15
      * 10(-9)), and a further 6 loci (4.50 * 10(-7) <= P <= 5.00 * 10(-5)) showed
      weaker evidence for association with increased specific IgE levels in the British
      1958 Birth Cohort. However, no SNPs studied showed consistent association with
      atopy defined by increased specific IgE levels, positive SPT responses, or both
      in all study cohorts. CONCLUSIONS: Seven putative atopy loci were identified
      using a genome-wide association study approach but showed limited replication
      across several white populations. This study suggests that large-scale analyses
      with results from multiple populations will be needed to reliably identify key
      genetic factors underlying atopy predisposition.

PMID- 21094522
TI  - Maternal folate levels in pregnancy and asthma in children at age 3 years.

PMID- 21094523
TI  - Rhinoconjunctival sensitization to hydrolyzed wheat protein in facial soap can
      induce wheat-dependent exercise-induced anaphylaxis.

PMID- 21094525
TI  - Neural responses to meaningless pseudosigns: evidence for sign-based phonetic
      processing in superior temporal cortex.
AB  - To identify neural regions that automatically respond to linguistically
      structured, but meaningless manual gestures, 14 deaf native users of American
      Sign Language (ASL) and 14 hearing non-signers passively viewed pseudosigns
      (possible but non-existent ASL signs) and non-iconic ASL signs, in addition to a
      fixation baseline. For the contrast between pseudosigns and baseline, greater
      activation was observed in left posterior superior temporal sulcus (STS), but not
      in left inferior frontal gyrus (BA 44/45), for deaf signers compared to hearing
      non-signers, based on VOI analyses. We hypothesize that left STS is more engaged
      for signers because this region becomes tuned to human body movements that
      conform the phonological constraints of sign language. For deaf signers, the
      contrast between pseudosigns and known ASL signs revealed increased activation
      for pseudosigns in left posterior superior temporal gyrus (STG) and in left
      inferior frontal cortex, but no regions were found to be more engaged for known
      signs than for pseudosigns. This contrast revealed no significant differences in
      activation for hearing non-signers. We hypothesize that left STG is involved in
      recognizing linguistic phonetic units within a dynamic visual or auditory signal,
      such that less familiar structural combinations produce increased neural
      activation in this region for both pseudosigns and pseudowords.

PMID- 21094524
TI  - Sirt3 mediates reduction of oxidative damage and prevention of age-related
      hearing loss under caloric restriction.
AB  - Caloric restriction (CR) extends the life span and health span of a variety of
      species and slows the progression of age-related hearing loss (AHL), a common age
      related disorder associated with oxidative stress. Here, we report that CR
      reduces oxidative DNA damage in multiple tissues and prevents AHL in wild-type
      mice but fails to modify these phenotypes in mice lacking the mitochondrial
      deacetylase Sirt3, a member of the sirtuin family. In response to CR, Sirt3
      directly deacetylates and activates mitochondrial isocitrate dehydrogenase 2
      (Idh2), leading to increased NADPH levels and an increased ratio of reduced-to
      oxidized glutathione in mitochondria. In cultured cells, overexpression of Sirt3
      and/or Idh2 increases NADPH levels and protects from oxidative stress-induced
      cell death. Therefore, our findings identify Sirt3 as an essential player in
      enhancing the mitochondrial glutathione antioxidant defense system during CR and
      suggest that Sirt3-dependent mitochondrial adaptations may be a central mechanism
      of aging retardation in mammals.

PMID- 21094527
TI  - Protein kinase C alpha enhances sodium-calcium exchange during store-operated
      calcium entry in mouse platelets.
AB  - A rise in intracellular calcium concentration ([Ca(2+)](i)) is necessary for
      platelet activation. A major component of the [Ca(2+)](i) elevation occurs
      through store-operated Ca(2+) entry (SOCE). The aim of this study was to
      understand the contribution of the classical PKC isoform, PKCalpha to platelet
      SOCE, using platelets from PKCalpha-deficient mice. SOCE was reduced by
      approximately 50% in PKCalpha(-/-) platelets, or following treatment with
      bisindolylmaleimide I, a PKC inhibitor. However, TG-induced Mn(2+) entry was
      unaffected, which suggests that divalent cation entry through store-operated
      channels is not directly regulated. Blocking the autocrine action of secreted ADP
      or 5-HT on its receptors did not reproduce the effect of PKCalpha deficiency. In
      contrast, SN-6, a Na(+)/Ca(2+) exchanger inhibitor, did reduce SOCE to the same
      extent as loss of PKCalpha, as did replacing extracellular Na(+) with NMDG(+).
      These treatments had no further effect in PKCalpha(-/-) platelets. These data
      suggest that PKCalpha enhances the extent of SOCE in mouse platelets by
      regulating Ca(2+) entry through the Na(+)/Ca(2+) exchanger.

PMID- 21094526
TI  - Adhesion/cementation to zirconia and other non-silicate ceramics: where are we
      now?
AB  - Non-silicate ceramics, especially zirconia, have become a topic of great interest
      in the field of prosthetic and implant dentistry. A clinical problem with use of
      zirconia-based components is the difficulty in achieving suitable adhesion with
      intended synthetic substrates or natural tissues. Traditional adhesive techniques
      used with silica-based ceramics do not work effectively with zirconia. Currently,
      several technologies are being utilized clinically to address this problem, and
      other approaches are under investigation. Most focus on surface modification of
      the inert surfaces of high strength ceramics. The ability to chemically
      functionalize the surface of zirconia appears to be critical in achieving
      adhesive bonding. This review will focus on currently available approaches as
      well as new advanced technologies to address this problem.

PMID- 21094528
TI  - Determinants of the endoplasmic reticulum (ER) lumenal-domain of the adenovirus
      serotype 2 E3-19K protein for association with and ER-retention of major
      histocompatibility complex class I molecules.
AB  - The E3-19K immunomodulatory protein from adenoviruses (Ads) inhibits antigen
      presentation by major histocompatibility complex (MHC) class I molecules. As a
      result, the ability of Ad-specific cytotoxic T lymphocytes (CTLs) to lyse
      infected cells is suppressed. The ER-lumenal domain of E3-19K is subdivided into
      a variable (residues 1 to ~78/81) and conserved (residues ~79/82 to 98) region
      followed by a linker (residues 99-107). Using molecular and cellular approaches,
      we characterized in detail the properties of the ER-lumenal domain of E3-19K that
      enable it to target MHC class I molecules. Proteolysis of recombinant serotype 2
      E3-19K (residues 1-100) (with six His residues) generated a large N-terminal
      (residues 1-88) and a small C-terminal fragment (residues 94-100) in solution.
      Neither of these fragments associates with HLA-A*1101 as shown by a native gel
      band-shift assay. In contrast, the N-terminal 1-93 residues of Ad2 E3-19K
      exhibited the same binding affinity to HLA-A*1101 as E3-19K. Using a site
      directed mutational analysis and flow cytometry, we show that Tyr(93), but not
      Tyr(88), critically modulates the cell-surface expression of MHC class I
      molecules. Taken together, these results indicate that the sequence comprising
      residues 89-93 (M(89)SKQY(93)), and in particular Tyr(93), in the conserved
      region of E3-19K is critical for its immunomodulatory function. Residues 89-93
      likely form a linker or loop in E3-19K. Overall, our data provide novel insights
      into the structure of E3-19K and identify key determinants for association with
      and ER-retention of its cellular target protein. This knowledge is important for
      our understanding of the molecular basis of Ad pathogenesis.

PMID- 21094529
TI  - CLEC5A (MDL-1) is a novel PU.1 transcriptional target during myeloid
      differentiation.
AB  - C-type lectin domain family 5, member A (CLEC5A), also known as myeloid DNAX
      activation protein 12 (DAP12)-associating lectin-1 (MDL-1), is a cell surface
      receptor strongly associated with the activation and differentiation of myeloid
      cells. CLEC5A associates with its adaptor protein DAP12 to activate a signaling
      cascade resulting in activation of downstream kinases in inflammatory responses.
      Currently, little is known about the transcriptional regulation of CLEC5A. We
      identified CLEC5A as one of the most highly induced genes in a microarray gene
      profiling experiment of PU.1 restored myeloid PU.1-null cells. We further report
      that CLEC5A expression is significantly reduced in several myeloid
      differentiation models upon PU.1 inhibition during monocyte/macrophage or
      granulocyte differentiation. In addition, CLEC5A mRNA expression was
      significantly lower in primary acute myeloid leukemia (AML) patient samples than
      in macrophages and granulocytes from healthy donors. Moreover, we found
      activation of a CLEC5A promoter reporter by PU.1 as well as in vivo binding of
      PU.1 to the CLEC5A promoter. Our findings indicate that CLEC5A expression in
      monocyte/macrophage and granulocytes is regulated by PU.1.

PMID- 21094531
TI  - Sexual orientation obsessions in obsessive-compulsive disorder: prevalence and
      correlates.
AB  - Sexual obsessions are a common symptom of obsessive-compulsive disorder (OCD)
      that may be particularly troubling to patients. However, little research has
      examined concerns surrounding sexual orientation, which includes obsessive doubt
      about one's sexual orientation, fears of becoming homosexual, or fears that
      others might think one is homosexual. The present study reports rates and related
      characteristics of individuals with sexual orientation obsessions in a clinical
      sample. Participants from the DSM-IV Field Trial (n=409; Foa et al., 1995) were
      assessed with the Yale-Brown Obsessive Compulsive Symptom Checklist and Severity
      Scale (YBOCS). We found that 8% (n=33) reported current sexual orientation
      obsessions and 11.9% (n=49) endorsed lifetime symptoms. Patents with a history of
      sexual orientation obsessions were twice as likely to be male than female, with
      moderate OCD severity. Time, interference, and distress items from the YBOCS
      obsessions subscale were significantly and positively correlated with a history
      of obsessions about sexual orientation. Avoidance was positively correlated at a
      trend level (p=0.055). Obsessions about sexual orientation may be associated with
      increased distress, interference, and avoidance, which may have unique clinical
      implications. Considerations for diagnosis and treatment are discussed.

PMID- 21094532
TI  - Therapeutic relationships in vocational rehabilitation: predicting good
      relationships for people with psychosis.
AB  - Therapeutic relationships between clients and vocational rehabilitation workers
      have been shown to predict entering competitive employment. We aimed to determine
      predictors of good relationships, using data from an international randomized
      controlled trial of supported employment (n=312). Baseline predictors of early
      therapeutic relationships with vocational workers were assessed, along with the
      impact of vocational status and changing clinical and social functioning
      variables on relationship ratings over time. Associations between client and
      professional relationship ratings were also explored. Better early client-rated
      therapeutic relationship was predicted by better baseline relationship with the
      clinical keyworker, being in the Individual Placement and Support (IPS) service,
      the absence of work history and a greater proportion of care needs being met,
      whereas over time it was predicted by being in the IPS service. Professional
      rated early relationship was predicted by social disability and remission, while
      over time it was predicted by being the same sex as the client, duration of the
      relationship and the client's increasing anxiety. Client and professional ratings
      were positively associated but clients' ratings were higher than professionals',
      particularly in the IPS service. Relationships were better where clients may have
      been more motivated to engage, including by their prior experience of a good
      therapeutic relationship with the clinical keyworker.

PMID- 21094530
TI  - Psychiatric context of human immunodeficiency virus infection among former plasma
      donors in rural China.
AB  - BACKGROUND: China's HIV epidemic commenced in its agrarian provinces through
      contaminated commercial plasma donation centers and is now becoming a public
      health concern nationwide. Little is known of the psychiatric and substance use
      disorder characteristics of this population, or their impact on everyday
      function, employment, and life quality. METHODS: HIV-infected (HIV+) former
      plasma donors (N=203) and HIV-negative (HIV-) donor controls (N=198) completed
      the World Mental Health Survey Composite International Diagnostic Interview to
      determine lifetime major depressive disorder (MDD), substance use disorders, and
      suicidality. Current mood and suicidality were assessed with the Beck Depression
      Inventory-II. Everyday function was measured by an Activity of Daily Living
      questionnaire; life quality was evaluated by the Medical Outcomes Study-HIV.
      RESULTS: HIV+ participants had known their infected status for 2 years on
      average. Most were taking antiretroviral treatment and had frank AIDS. Rates of
      current MDD were similar across groups (1-2%), but HIV+ had a higher frequency of
      lifetime MDD (14% vs. 5%, p<.05). Its onset preceded date of known infection in
      one-third of cases. Alcoholism was the only substance use disorder detected; HIV+
      had a higher proportion of lifetime substance use diagnoses (14% vs. 6%, p<.05).
      Depression and AIDS independently predicted worse daily functioning and life
      quality, and unemployment. LIMITATIONS: The epicenter of China HIV has moved into
      urban injection drug users, limiting the representativeness of this sample.
      CONCLUSIONS: High rates of MDD and its impact suggest that in China, as
      elsewhere, comprehensive care requires detection and treatment of mood disorder.

PMID- 21094533
TI  - Affective dysfunctions in adolescents at risk for psychosis: emotion awareness
      and social functioning.
AB  - Studies of individuals at ultra high risk (UHR) for psychosis have revealed
      deviations in cognitive and neural development before the onset of psychosis. As
      affective impairments are among the core dysfunctions in psychotic disorders such
      as schizophrenia, this study assessed emotion processing and the relationship
      with social competence in adolescents at risk for psychosis. Thirty-four
      adolescents at UHR for psychosis and twenty-three non-clinical controls completed
      the Bermond-Vorst Alexithymia Questionnaire, a measure of emotion awareness.
      Social inadequacy was measured using the Dutch Personality Questionnaire.
      Schizophrenia spectrum psychopathology was assessed using self-report and
      clinical instruments. The Wechsler Adult Intelligence Scale (WAIS) was used to
      evaluate intellectual functioning. UHR adolescents showed difficulties in
      identifying and verbalizing their own emotions, independent of intelligence
      scores. Emotion awareness problems were related to social inadequacy and
      schizotypal traits in the high risk group. These findings suggest that UHR
      adolescents may have reduced emotion awareness, independent of intellectual
      functioning. The relationship with social inadequate behavior fits with the idea
      that emotion awareness is a prerequisite for the regulation of emotions in social
      contexts. In the search for early vulnerability markers of risk for psychosis,
      studying emotion processing besides cognitive abilities might increase our
      understanding of 'at risk' developmental pathways.

PMID- 21094534
TI  - CSF rhinorrhea-feasibility of conservative management in children.
AB  - PURPOSE: To study the role of conservative management in CSF rhinorrhea in
      pediatric population. STUDY DESIGN: A retrospective study in a tertiary care
      center. METHODS: Cases with a diagnosis of CSF rhinorrhea discharged after
      conservative management but required skull base repair for recurrence of CSF
      rhinorrhea or meningitis were included in the study between periods 2000 and July
      2010. RESULTS: 12 cases of CSF rhinorrhea managed were treated conservatively, 7
      patients again required rehospitalisation for recurrence of CSF rhinorrhea or
      meningitis. Male:female ratio was 4:1. The age ranged from 3 years to 14 years.
      Duration of recurrence of the CSF leak or meningitis varied from 6 to 121 months.
      Presenting symptoms included headache, rhinorrhea, or recurrent meningitis. The
      time from the initial injury to surgical exploration ranged from 163 to 3650
      days. All patients were under regular follow-up and doing well except one had
      recurrence of the leak 2 months after surgery requiring revision surgery
      following which the patient had no recurrence. DISCUSSION: The management of CSF
      fistulae is still a matter of debate and there will be a risk of recurrent
      meningitis on conservative management. Most comprehensive study to date indicates
      there is a 9.8% annual risk of developing meningitis. Duration of recurrence of
      the CSF leak or meningitis varied from 6 months to 121 months. The overall
      incidence of meningitis as a result of skull base defect and CSF leak ranges from
      9% to 50% with a reported cumulative risk of 85% in 10 years if no repair is
      performed. As seen in our series CSF repair can resolve with conservative
      management but there is a risk of intermittent CSF leak or meningitis due to an
      incompletely healed or tenuous mucosal regeneration which should be addressed
      surgically. The patients with traumatic CSF leak who were treated with
      conservative management alone had a 25-29% risk of subsequent meningitis.
      CONCLUSION: Conservative treatment of CSF leaks may lead to recurrent meningitis
      or leaks, therefore surgical closure of defects at the skull base should be
      considered treatment of choice to prevent ascending meningitis.

PMID- 21094535
TI  - The expression of plasma membrane Ca(2+)-ATPase isoform 2 and its splice variants
      at sites A and C in the neonatal rat cochlea.
AB  - OBJECTIVE: To study the expression of plasma membrane Ca(2+)-ATPase isoform 2
      (PMCA2) and its alternative splicing at sites A (the first intracellular loop)
      and C (the C-terminal region) in the neonatal rat cochlea. METHODS: The cochleae
      from rats postnatal day 3 to postnatal day 4 (P3-P4) were dissected, fixed,
      embedded, and sectioned. Meanwhile, the cochlear coils from neonatal rats were
      isolated and fixed. Using immunofluorescence staining, the expression of PMCA2
      was respectively examined in the cochlear sections and cochlear coils. In
      addition, the total RNAs of basilar membrane (BM, including the organ of corti,
      the same below), spiral ganglion (SG), spiral ligament (SL, including SV, the
      same below), and the whole cochlea from neonatal rats were respectively extracted
      and reverse transcribed to cDNAs, then subjected to primers flanking site A or C
      in the PMCA2 gene using reverse transcription polymerase chain reaction (RT-PCR).
      Western blot was also applied to detect the expression of PMCA2 isoforms in the
      cochlear tissues. RESULTS: We found that PMCA2 is strongly expressed in outer
      hair cell (OHC) bundles, SG, and stria vascularis (SV), weakly expressed in
      Reissner's membrane (RM), and occasionally expressed in inner hair cell (IHC)
      bundles. Moreover, w/a is the major splice form of PMCA2 present in hair cell
      bundles, z/b and z/c are the major splice forms of PMCA2 present in SG, and w/a
      and w/c are the major splice forms of PMCA2 present in SV. In the whole cochlea,
      variants w, y, and z were detected at site A, and variants a, b, and c were
      detected at site C. Using Western blot, variant a or b was also detectable in the
      same cochlear tissues mentioned above. CONCLUSIONS: PMCA2 and its splice variants
      at sites A and C are differentially expressed in cochlear tissues of neonatal
      rat.

PMID- 21094536
TI  - Cholesterol, vitamin D and cardiovascular prevention in HIV patients treated with
      antiretroviral therapy.

PMID- 21094537
TI  - The influence of diabetes on novel electrocardiographic indexes of arrhythmic
      risk in patients with stable coronary artery disease.

PMID- 21094538
TI  - Acute myocarditis after urinary tract infection by Escherichia coli.

PMID- 21094539
TI  - The influence of inflammation outweighing the metabolic syndrome on
      cardiovascular risk and mortality.

PMID- 21094540
TI  - Coronary plaque components assessed by virtual histology-intravascular ultrasound
      are not associated with neointimal hyperplasia in patients who underwent drug
      eluting stent implantation.

PMID- 21094541
TI  - The older patient with syncope: practicalities and controversies.
AB  - The prevalence of syncope, in particular cardiac syncope, increases with
      advancing age and is associated with significant morbidity and mortality.
      Diagnosis of syncope within this population can be complex due to atypical
      presentations, amnesia for events and the overlap with falls. Thus, a lower
      threshold for investigation, preferably within a specialist syncope service, is
      necessary. Investigations for neurally mediated syncope, such as head-up tilt
      table testing, are well tolerated in the older patients, while advances in auto
      activated cardiac monitoring devices have increased the diagnostic yield for
      cardiac syncope. The treatment of syncope ranges from simple conservative
      measures through to permanent cardiac pacing. This is a review of the existing
      literature highlighting the epidemiology, aetiology, clinical features,
      investigation and management strategies of syncope in the older population.

PMID- 21094542
TI  - Obstructive sleep apnea may increase the risk of stroke in AF patients: refining
      the CHADS2 score.

PMID- 21094543
TI  - Significance of postprocedural cardiac biomarker elevations in patients with
      elective stent implantation.

PMID- 21094544
TI  - Non-ischemic dilated cardiopathy: prognostic value of functional mitral
      regurgitation.

PMID- 21094545
TI  - Epicardial fat thickness and coronary artery disease correlate independently of
      obesity.

PMID- 21094546
TI  - Intestinal barrier function in patients with acute myocardial infarction and the
      therapeutic effect of glutamine.

PMID- 21094547
TI  - Carbamylated low-density lipoprotein increases reactive oxygen species (ROS) and
      apoptosis via lectin-like oxidized LDL receptor (LOX-1) mediated pathway in human
      umbilical vein endothelial cells.

PMID- 21094548
TI  - Accordion phenomenon induced by pressure wire.

PMID- 21094549
TI  - Effects of a short-term exercise training on serum factors involved in
      ventricular remodelling in chronic heart failure patients.
AB  - OBJECTIVES: We studied the effect of a short-term (3 weeks) exercise training
      program on the number of circulating CD34/KDR(+) endothelial progenitor cells
      (EPCs) and on serum levels of matrix metalloproteinases (MMPs) in chronic heart
      failure (CHF) patients as well as on serum capacity to foster colony forming
      units-endothelial cells (CFU-ECs) in vitro. METHODS: Effectiveness of training
      was assessed by the 6-minute walking test (6MWT). Peripheral blood and serum were
      obtained from fourteen patients with CHF due to coronary artery disease before
      and after an inpatient aerobic exercise training program. At admission and at
      discharge we analysed circulating EPC number and serum levels of MMPs, TIMP-1 and
      TNF-alpha. The number and function of CFU-EC colonies were evaluated in cultures
      performed with serum obtained before and after training. RESULTS: After training,
      distance walked at 6MWT and number of circulating CD34/KDR(+) cells increased
      (from 154 +/- 27 to 233 +/- 48 m; P<0.0001 and from 5 +/- 3 to 9 +/- 6 cells/ml
      P<0.05, respectively). Conversely, serum concentrations of MMP-1 and TIMP-1
      decreased significantly (from 11.4 +/- 2.4 to 6.3 +/- 1.1 ng/ml, and from 320.4
      +/- 41.2 to 167.2 +/- 12.6 ng/ml, respectively, both P<0.01), while MMP2/TIMP-1
      and MMP-9/TIMP-1 ratios increased. Interestingly, we found increased CFU-EC
      proliferation in cultures performed with serum obtained after training.
      CONCLUSIONS: Considering that both EPCs and MMPs might play a role in vascular
      remodeling, the increased number of EPCs and MMP activities observed in this
      study, suggest that the selected short-term exercise training could be a
      potential therapeutic strategy to rescue cardiac function in CHF patients.

PMID- 21094550
TI  - End-of-life in adults with congenital heart disease: a call for early
      communication.
AB  - BACKGROUND: We investigated preferences of adults with congenital heart disease
      (CHD) and their health care providers regarding end-of-life (EOL) communication.
      METHODS: Adult CHD outpatients and health care providers completed surveys about
      preferences for and experiences with EOL communication. Responses were compared
      between patients and providers. RESULTS: Two hundred patients (18-79 years) and
      48 CHD health care providers (primarily cardiologists) completed surveys. Only 2
      patients (1%) indicated that they had discussed EOL planning with their medical
      team. In contrast, 50% of providers reported that they typically discuss issues
      including life expectancy, advance planning, and resuscitation preferences with
      their outpatients. Seventy-eight percent (156/199) of patients wanted their
      medical team to raise EOL issues; this preference was independent of disease
      complexity and socio-demographic factors. In contrast, providers reported that
      their EOL discussions increase in accordance with disease complexity (p<0.001).
      Early initiation of EOL discussions, before diagnosis with life-threatening
      complications, was favored by 62% of patients but only 38% of providers
      (p<0.001). CONCLUSION: Health professionals caring for adults with CHD should
      explore preferences of their patients for EOL discussions earlier in the disease
      course, and not only with patients facing life-threatening complications and/or
      with complex conditions. When EOL discussions do occur, health care providers
      should attempt to ensure that patients better understand these conversations.
      Increased attention to EOL issues is proposed in order to improve the care of
      patients with CHD across the lifespan.

PMID- 21094551
TI  - The complex interplay of cardiovascular system and cognition: how to predict
      dementia in the elderly?
AB  - Prevalence of dementing illnesses is expected to grow due to aging of the
      population throughout the world. Vascular dementia and Alzheimer's disease share
      several risk factors and are nowadays considered two ends of a continuum rather
      than two distinct entities. Traditional cardiovascular risk markers such as
      diabetes, dyslipidemia, hypertension, metabolic syndrome and adiposity in mid
      life are harbingers of cognitive decline, Alzheimer's disease and vascular
      dementia later in life. In aged populations, only diabetes has been more
      constantly associated with the development of cognitive dysfunction, while other
      risk markers have shown more mixed results. Normal aging, co-morbidities and
      other changes connected to cognitive decline make the interpretation of the risk
      markers in the elderly challenging and probably explain these contradictory
      findings. Control of cardiovascular risk factors has been linked to beneficial
      effects in terms of cognition in cross-sectional and prospective follow up
      studies, but the results of interventional trials have been disappointing. More
      research in this area is needed, specifically, placebo-controlled randomized
      trials in both mid-life and late-life with cognitive dysfunction as a primary
      endpoint.

PMID- 21094552
TI  - The long term financial impacts of CVD: living standards in retirement.
AB  - BACKGROUND: Cardiovascular disease (CVD) has significant economic costs, however
      these are generally estimated for the present-time and little consideration is
      given to the long term economic consequences. This study estimates the value of
      savings those who retire early due to CVD will have accumulated by the time they
      reach the traditional retirement age of 65 years, and how much lower the value of
      these savings are compared to those who remained healthy and in the workforce.
      METHODS: Using Health&WealthMOD - a microsimulation model of Australians aged 45
      to 64 years, regression models were used to analyse the differences between the
      projected savings and the retirement incomes of people by the time they reach age
      65 for those currently working with no chronic condition, and people not in the
      labour force due to CVD. RESULTS: Over 99% of individuals who are employed full
      time will have accumulated some savings at age 65; whereas only 77% of those who
      are out of the labour force due to CVD will have done so. Those who retire early
      due to CVD will have a median value of total savings by the time they are 65 of
      $1833. This is far lower than the expected median value of savings for those who
      remained in the labour force full-time, who will have $281841 of savings.
      CONCLUSIONS: Not only will early retirement due to cardiovascular disease limit
      the immediate income and wealth available to individuals, but also reduce their
      long term financial capacity by reducing their savings.

PMID- 21094553
TI  - Effect of a low glycaemic index diet on blood glucose in women with gestational
      hyperglycaemia.
AB  - AIM: The objectives of this pilot study were to determine the feasibility and
      effect on glycaemic control of a low-glycaemic-index (GI) diet in women with
      gestational diabetes or impaired glucose tolerance of pregnancy. METHODS:
      participants, recruited from the Diabetes-in-Pregnancy Clinic of an inner-city
      teaching hospital serving a predominantly non-Caucasian population, were
      randomized to a low-GI (n=23) or control (n=24) diet and followed from 28 weeks
      gestation until delivery. Self-monitored-blood-glucose (SMBG), maternal and
      infant weight were collected from medical charts. Dietary intakes were assessed
      using diet records and questionnaires. RESULTS: diet GI on control (58, 95% CI:
      56,60) was significantly higher than on low-GI (49, 95% CI: 47,51; p=0.001).
      Glycaemic control improved on both diets, but more postprandial glucose values
      were within target on low-GI (58.4% of n=1891) than control (48.7% of n=1834;
      p<0.001). SMBG post-breakfast was directly related to pre-pregnancy BMI in the
      control, but not the low-GI group (BMI*diet interaction; p=0.021). Participants
      accepted the study foods and were willing to consume them post-intervention.
      CONCLUSIONS: a low-GI diet was feasible and acceptable in this sample and
      facilitated control of postprandial glucose. A larger study is needed to
      determine the effect of a low-GI diet on maternal and infant outcomes.

PMID- 21094554
TI  - Efficiency of oxidative phosphorylation in liver mitochondria is decreased in a
      rat model of peritoneal carcinosis.
AB  - BACKGROUND & AIMS: Cancer cachexia is a dynamic process characterized by a
      negative energy balance induced by anorexia and hypermetabolism. The mechanisms
      leading to hypermetabolism are not totally elucidated. This study examines the
      efficiency of oxidative phosphorylation and energy wasting in liver mitochondria
      isolated from rats with cancer cachexia induced by peritoneal carcinosis (PC).
      METHODS: PC was generated by an intraperitoneal injection of cancer cells (PROb)
      in BDIX rats. The efficiency of oxidative phosphorylation and energy wasting as
      well as the role played by reactive oxygen species (ROS) and cardiolipin
      (mitochondrial inner membrane phospholipid) in these processes were assessed in
      liver mitochondria of PC and pair-fed control rats. RESULTS: The efficiency of
      oxidative phosphorylation decreased (-26%) while energy wasting increased (+22%)
      in liver mitochondria from PC compared to control rats. The increased energy
      wasting was associated with a higher cardiolipin content (+55%, p<0.05;
      R(2)=0.64, p<0.05) and with a lower n-6/n-3 polyunsaturated fatty acid ratio in
      cardiolipin (-45%, p<0.05; R(2)=0.21, p<0.05) in PC rats. ROS production was
      increased by 12-fold in liver mitochondria from PC rats. CONCLUSIONS: The
      efficiency of ATP synthesis was reduced and energy wasting processes were
      increased in liver mitochondria of PC rats. This suggests that liver mitochondria
      from PC rats request more nutrients than liver mitochondria from control rats to
      maintain the same ATP production. These alterations were associated to the
      content and fatty acid composition of cardiolipin.

PMID- 21094555
TI  - Management of hepatocellular adenoma during pregnancy.
AB  - BACKGROUND & AIMS: Hepatocellular adenoma in pregnant women requires special
      considerations because of the risk of hormone induced growth and rupture. To
      prevent these potential lethal complications, pregnancy is either often
      discouraged or the surgical resection of large adenomas is recommended. It may be
      questioned whether it is justified to deny a young woman a pregnancy, as the
      biological behaviour of hepatocellular adenoma may be less threatening than
      presumed. In this study we establish the management of hepatocellular adenoma
      during pregnancy based on our own experience and literature. METHODS: Twelve
      women with documented hepatocellular adenoma were closely monitored during a
      total of 17 pregnancies between 2000 and 2009. Their files were reviewed.
      RESULTS: In four cases, hepatocellular adenomas grew during pregnancy, requiring
      a Caesarean section in one patient (two pregnancies) at 36 and 34 weeks because
      of an assumed high risk of rupture. In one case radiofrequency ablation therapy
      was applied in the first trimester to treat a hormone sensitive hepatocellular
      adenoma, thereby excluding potential growth later in pregnancy. No intervention
      was performed in the other 14 cases and all pregnancies had an uneventful course
      with a successful maternal and fetal outcome. CONCLUSIONS: A "wait and see"
      management may be advocated in pregnant women presenting with a hepatocellular
      adenoma. In women with large tumours or in whom hepatocellular adenoma had
      complicated previous pregnancies, surgical resection may be recommended. In women
      with smaller adenomas it may no longer be necessary to discourage pregnancy.

PMID- 21094556
TI  - G80S-linked ferroportin disease: classical ferroportin disease in an Asian family
      and reclassification of the mutant as iron transport defective.
AB  - BACKGROUND & AIMS: Hereditary iron overload associated with mutations in the
      ferroportin gene produces a dichotomy of phenotypes resulting from either
      increase or decrease in iron efflux capacity. In this study, we examined the
      molecular basis of iron overload in a family of Vietnamese origin, characterized
      the molecular and cellular defect, and correlated it with the clinical and
      pathological phenotype. METHODS: We analyzed the ferroportin gene by DNA
      sequencing. The molecular characterization was performed by immunofluorescence
      microscopy analysis of transfected cells. We analyzed ferritin levels, in cells
      expressing wild-type and mutant ferroportin, to define the nature of the
      molecular defect in iron transport. RESULTS: We identified a G to A nucleotide
      change at position 238 in the ferroportin gene leading to the G80S substitution.
      Cellular analysis of the mutant protein indicates that this amino acid change
      does not affect the localization of the protein but does affect its ability to
      transport iron. CONCLUSIONS: The G80S mutation results in a mutated ferroportin
      associated with iron overload and is predicted to be defective in iron export.

PMID- 21094557
TI  - Physician dual practice: a review of literature.
AB  - OBJECTIVES: A combination of public and private practice by physicians, referred
      to as physician dual practice, has been receiving attention in connection with
      arguments about its negative impact for the public health care. This paper aims
      to review and critically discuss findings on the subject of dual practice effects
      for the public health care. METHODS: A systematic literature review identified 23
      positions on the subject consisting of journal articles, academic working papers,
      book chapter, and publications of the WHO. RESULTS: The subject is short on
      evidence. Theoretical analyses indicate both positive and negative effects of
      dual practice. Some of the effects depend, however, on assumptions that are
      undermined in the broader literature. The analyses assume that the dual
      practitioners' objective is to maximise income. Yet, while physicians seem to
      engage in a private practice on top of the public one mainly to increase income,
      it remains uncertain whether dual practice is an income-maximising combination of
      jobs. Moreover, costs of enforcing restrictions on dual practice are rarely
      considered. CONCLUSIONS: Further research is needed that compares dual
      practitioners and other physicians in uniform settings, investigates how the dual
      practitioners divide labour between the two jobs, and analyses the costs of
      enforcing restrictions on dual practice.

PMID- 21094558
TI  - Psychosocial factors associated with the prescription of generic drugs.
AB  - OBJECTIVE: To evaluate factors associated with "Generic drug prescription" (GDP)
      behaviour in Spain using the ASE (Attitude, Social Influence, Self-Efficacy)
      Model. METHODS: General Practitioners were sent a validated and anonymous
      questionnaire measuring the ASE and Motivation variables for GDP and their
      generic drug prescription percentage. Most (n=486; 61.98%) responded to this
      cross-sectional survey. The mean scores and the 95% confidence intervals (95% CI)
      were calculated. A binary logistic regression was used to identify the variables
      that best predict GDP behaviour. RESULTS: The main advantages and motivations for
      GDP were "saving money" and "protecting professional ethics". The greatest social
      influences were "doctors' personal preferences" and "authorities' pressure". GDP
      accounted for a scarce 15% of the total prescription. ASE and Motivation items
      were the best predictors: they explain 25% of being a 'high prescriber'. The
      highest prescribers were paediatricians (OR=5.07), workers in rural settings
      (OR=3.68) and professionals with high Motivation (OR=1.17) and Attitude (OR=1.11)
      scores. CONCLUSIONS: GDP percentage is very low compared with other countries.
      Interventions to modify the Attitudes of Primary Care doctors towards generic
      drugs should be implemented. Better informed patients, longer doctor appointment
      times and more varied dosage forms of generic drugs would also facilitate
      improvements in GDP.

PMID- 21094559
TI  - Optimal anatomic coverage for CT in staging lung cancer: lessons from PET-CT
      correlation.
AB  - OBJECTIVE: To determine the optimal anatomic coverage at CT that would provide
      the most accurate staging for patients with non-small cell lung cancer. METHODS:
      We reviewed lung cancer staging PET-CT scans and correlated them with staging
      chest CT scans performed within 50 days of the PET-CT study. There were 113
      patients who underwent both studies within our time frame. We reviewed the
      results of subsequent imaging studies and surgical and biopsy procedures to
      determine the final stage for each patient. This study was approved by the local
      institutional review board. RESULTS: In 86 (76%) of 113 patients, staging by PET
      CT and by CT from the lung apices through the lung bases was identical. PET-CT
      upstaged 21 patients (19%) compared with CT findings; in 13 of these patients the
      PET-CT noted disease that was either outside of the anatomic range of any lung
      cancer staging CT or was within the area scanned by CT, but was not evident by
      CT. In the other 8 upstaged patients, extending the anatomic scope of the CT scan
      to the supraclavicular region (5), adrenal glands (2) or abdomen (1) would have
      resulted in correct staging. CONCLUSIONS: CT scanning from the supraclavicular
      region through the caudal adrenal glands improves the accuracy of CT staging of
      lung cancer compared with scanning from the lung apices through the lung bases.
      Anatomic coverage beyond the adrenal glands has a low yield for improved staging,
      at the cost of requiring administration of oral contrast to all patients.
      SUMMARY: To determine the optimal anatomic coverage at CT that would provide the
      most accurate staging for patients with non-small cell lung cancer, we reviewed
      lung cancer staging PET-CT scans and correlated them with staging chest CT scans
      performed within 50 days of the PET-CT study. CT scanning from the
      supraclavicular region through the caudal adrenal glands improves the accuracy of
      CT staging of lung cancer compared with scanning from the lung apices through the
      lung bases. Anatomic coverage beyond the adrenal glands has a low yield for
      improved staging, at the cost of requiring administration of oral contrast to all
      patients undergoing lung cancer staging.

PMID- 21094560
TI  - Mobile teledermatology in the developing world: implications of a feasibility
      study on 30 Egyptian patients with common skin diseases.
AB  - BACKGROUND: The expansion of store-and-forward teledermatology into underserved
      regions of the world has long been hampered by the requirement for computers with
      Internet connectivity. To our knowledge, this study is one of the first to
      demonstrate the feasibility of teledermatology using newer-generation mobile
      telephones with specialized software and wireless connectivity to overcome this
      requirement in a developing country. OBJECTIVE: We sought to demonstrate that
      mobile telephones may be used on the African continent to submit both patient
      history and clinical photographs wirelessly to remote expert dermatologists, and
      to assess whether these data are diagnostically reliable. METHODS: Thirty
      patients with common skin diseases in Cairo, Egypt, were given a diagnosis by
      face-to-face consultation. They were then given a diagnosis independently by
      local senior dermatologists using teleconsultation with a software-enabled mobile
      telephone containing a 5-megapixel camera. Diagnostic concordance rates between
      face-to-face and teleconsultation were tabulated. RESULTS: Diagnostic agreement
      between face-to-face consultation and the two local senior dermatologists
      performing independent evaluation by teleconsultation was achieved in 23 of 30
      (77%) and in 22 of 30 (73%) cases, respectively, with a global mean of 75%.
      LIMITATIONS: Limited sample size and interobserver variability are limitations.
      CONCLUSION: Mobile teledermatology is a technically feasible and diagnostically
      reliable method of amplifying access to dermatologic expertise in poorer regions
      of the globe where access to computers with Internet connectivity is unreliable
      or insufficient.

PMID- 21094561
TI  - Evaluation of quality of life questionnaires for adult patients with moderate to
      severe allergic rhinitis.
AB  - PURPOSE: The aim of the study was to compare the efficacy of instruments to
      assess quality of life (QoL) in patients with moderate to severe persistent
      allergic rhinitis (PAR) vs intermittent allergic rhinitis (IAR). MATERIALS AND
      METHODS: There were 106 patients with PAR and 99 with IAR and 50 healthy subjects
      in the control group. Questionnaire results were obtained using the Medical
      Outcomes Survey Short Form 36 (SF-36), a visual analog scale (VAS), and the
      rhinoconjunctivitis quality of life questionnaire (RQLQ) and were analyzed using
      correlational analysis. RESULTS: Correlations between the total scores and most
      domains of the 3 questionnaires were stronger in patients with PAR than in those
      with IAR, although the difference between groups was significant only for the
      RQLQ (P < .01). The QoL was worse in the PAR subgroup than in the IAR subgroup in
      the domains of social functioning in the SF-36 and for items of sleeping problems
      and activity limitations in the RQLQ. There were significant correlations between
      RQLQ and VAS-eye symptoms in the PAR subgroup but not in the IAR subgroup.
      CONCLUSIONS: The 3 questionnaires differentiated patients with AR from the
      healthy population, with significant but weak correlation with each other. The
      correlations were higher in patients with PAR than in those with IAR. The
      moderate to severe PAR has a greater effect on quality of life than IAR. Eye
      symptoms affected the QoL more in patients with PAR than in those with IAR.

PMID- 21094562
TI  - [Public health crises in a developed society. Successes and limitations in Spain.
      SESPAS report 2010].
AB  - The perception, acceptability and management of risks are social construction.
      Consequently, in managing public health crises, the gap between facts, beliefs
      and feelings tests the responsiveness of official institutions to health alarms
      that can be objective, potential, or imaginary. On balance, a strong point of the
      Spanish experience of health crises is the presence of clinicians and public
      health officers working in an organization capable of responding adequately,
      although the quasi-federal Spanish political structure has both advantages and
      disadvantages. Weaknesses include the low profile given to public health and a
      management structure that relies too heavily on partitocracy. The management of
      these crises could be improved by transferring greater scope to health
      professionals in decisions about crisis identification and management (with
      transparency) and limiting bureaucratic inertia. For some, health crises involve
      visibility or business opportunities (not always legitimate). Therefore, the
      perception of crisis will increasingly rest less in the hands of experts and more
      in those of groups interested in spreading these crises or in providing
      solutions. While progress is needed to develop participation in strategies to
      respond to emerging crises, even more essential is the involvement of all
      healthcare levels in their preparation and dissemination.

PMID- 21094563
TI  - Synthesis, characterization and cytotoxicity studies of methoxy alkyl substituted
      metallocenes.
AB  - Five titanocene derivatives and one zirconium analogous, having
      cyclopentadienylethenylmethoxy ligand, were synthesized and fully characterized
      by NMR, FT-IR, and elemental analysis. Two of these complexes showed a good
      cytotoxic activity on human breast cancer (MCF-7) cell lines. Moreover, the half
      titanocene disclosed also a good cytotoxic activity on human embryonic kidney
      (HEK-293). Additionally, a study on the rate of hydrolysis of these compounds
      showed that the leaving groups significantly affect the rate of hydrolysis of
      cyclopentadienyl groups too. The different activity of synthesized compounds was
      tentatively related to the rate of hydrolysis.

PMID- 21094564
TI  - Synthesis and antimycobacterial activity of a series of ferrocenyl derivatives.
AB  - In this work we reported the synthesis and evaluation of Mycobacterium
      tuberculosis activities in vitro of a series of twenty five ferrocenyl
      derivatives: ferrocenyl amides derived from nicotinamide and pyrazinamide,
      ferrocenyl pyridinyl, quinolyl and acridinylhydrazones. In particular ferrocenyl
      acylhydrazones 7 and 8 and ferrocenylquinoxaline amide 57 showed interesting
      antimycobacterial activities.

PMID- 21094565
TI  - Discovery of highly potent agents against influenza A virus.
AB  - We previously reported several new M2 inhibitors as active as amantadine against
      influenza A virus and validated by three types of in vitro assays. Herein, we
      further modified one of the most potent hits in a viral inhibition assay and
      conducted structure-activity relationship studies on this scaffold. As a result,
      compound 8e was identified to be the most potent inhibitor against wild-type
      influenza A virus, being nearly 240-fold more active than amantadine.

PMID- 21094566
TI  - The role of faculty and clinical practice in predicting why nurses graduate in
      Hungary.
AB  - AIMS: to estimate the proportion of nursing students in Hungary who intend to
      graduate from a nursing program and intend to work as a nurse after graduation.
      METHODS: a cross-sectional, mail survey was implemented. A total of 381,
      purposively selected, final year students returned the survey instrument
      developed by the researchers. The survey was conducted in 3 of the total 7
      nationwide nursing schools. RESULTS: the rate of estimated student attrition
      ranged between 7 and 20%. Students were most satisfied with the mentoring and
      support received from faculty, and were least satisfied with their future career
      as a nurse. The most important factors that predicted intent to graduate and work
      after graduation were satisfaction with faculty support and clinical experiences,
      influence from family/peers to leave nursing, and intent to work abroad.
      CONCLUSIONS: self-reported student attrition was prevalent in the sample studied.
      Students ranked faculty support as the top influence to graduate and work as a
      nurse after graduation. The finding that family/peers had negative influence on
      students' intent to graduate requires further exploration. Provision of strong,
      continuous support to faculty members by the school administration seems the
      best, but not the only counter attack against student attrition.

PMID- 21094567
TI  - Taking up the challenge for nurse education research and scholarship.

PMID- 21094568
TI  - Use of reciprocating rasp in articular eminectomy.

PMID- 21094569
TI  - Transdiagnostic cognitive processes in high trait anger.
AB  - Trait anger is a personality construct that refers to stable individual
      differences in the propensity to experience anger as an emotional state. The
      objective of this paper is to review relevant empirical studies in order to
      determine whether the transdiagnostic cognitive processes that have been
      identified across the DSM-IV Axis I disorders (specifically, selective attention,
      memory biases, reasoning biases and recurrent negative thinking) are also an
      underlying characteristic of high trait anger. On the basis of the review it is
      concluded that, whilst the research base is limited, there is good evidence that
      high trait anger is associated with selective attention to hostile social cues,
      the tendency to interpret the behaviour of others as indicating potential
      hostility and the tendency to ruminate over past anger-provoking experiences. The
      range of cognitive processes identified in high trait anger is consistent with
      those identified in the Axis I disorders. It is concluded that these findings
      provide support for (i) the broad applicability of the transdiagnostic approach
      as a theoretical framework for understanding a range of psychological conditions,
      not limited to the Axis I disorders, and (ii) the validity of conceptualising
      high trait anger as an aspect of personality functioning that is maintained, at
      least in part, by cognitive processes. Cognitive and motivational factors
      (specifically, beliefs and goals) that may underlie the hostile information
      processing biases and recurrent negative thinking associated with high trait
      anger are discussed, and consideration is given to the clinical relevance of the
      findings of the review.

PMID- 21094570
TI  - Use of the zygomatic arch for stable anchorage in minimal access cranial
      suspension lifting.

PMID- 21094571
TI  - Juxtacortical osteogenic sarcoma of the jaws: case report and review of the
      literature.

PMID- 21094572
TI  - Application of rapid prototyping for temporomandibular joint reconstruction.
AB  - PURPOSE: To introduce the preliminary application of rapid prototyping (RP) for
      temporomandibular joint (TMJ) surgery. MATERIALS AND METHODS: This study included
      11 consecutive patients (13 joints) seeking TMJ replacement. All patients had
      previously undergone 3-dimensional computed tomography (CT) scanning (0.625-mm
      slice thickness) of the craniofacial skeleton. The data from CT scanning in DICOM
      (Digital Imaging and Communications in Medicine) format were input into the
      interactive Simplant CMF software program (Materialise Medical, Leuven, Belgium).
      Preoperative planning included segmentation and osteotomies. The movements of the
      jaw bones were simulated by use of Simplant CMF. The affected mandible was
      reconstructed based on the contralateral side. Then, the titanium plate was
      shaped on the reconstructed model before surgery. The bone graft was transplanted
      by the shaped titanium plate during the operation to reconstruct the TMJ. Twenty
      four patients who underwent traditional surgery were used as the control group.
      The operative time of the 2 groups was analyzed with the SPSS software package,
      version 13.0 (SPSS, Chicago, IL), with the Student t test. The data from CT
      scanning in the experimental group before and after surgery were compared by
      paired t test. RESULTS: All the incisions healed primarily without any
      complications. All patients were satisfied with the operation, because of their
      symmetric faces and good occlusion. Postoperative magnetic resonance imaging
      confirmed the position of the transplanted costochondral cartilage in the glenoid
      fossa. A group t test showed that the operative time was longer in the control
      group (mean, 7.09 hours) than that in the RP group (mean, 5.67 hours). Three
      parameters (condyle-incisor, condyle-mental foramen, and condyle-angle) from the
      postoperative CT scan were analyzed by paired t test, and there was no
      significant difference between the 2 sides. CONCLUSION: RP technology provides an
      advanced method for TMJ reconstruction that can make the TMJ reconstruction more
      accurate and symmetric, improve the mandible's function, and consequently,
      enhance the reconstructive effect.

PMID- 21094573
TI  - Decreased load on general motor preparation and visual-working memory while
      preparing familiar as compared to unfamiliar movement sequences.
AB  - Learning movement sequences is thought to develop from an initial controlled
      attentive phase to a more automatic inattentive phase. Furthermore, execution of
      sequences becomes faster with practice, which may result from changes at a
      general motor processing level rather than at an effector specific motor
      processing level. In the current study, we examined whether these changes are
      already present during preparation. Fixed series of six keypresses, either
      familiar or unfamiliar, had to be prepared and executed/withheld after a go/nogo
      signal. Reaction time results confirmed that familiar sequences were executed
      faster than unfamiliar sequences. Results derived from the electroencephalogram
      showed a decreased demand on general motor preparation and visual-working memory
      before familiar sequences as compared to unfamiliar sequences. We propose that
      with familiar sequences the presetting segments of responses is less demanding
      than with unfamiliar sequences, as familiar sequences can be regarded as less
      complex than unfamiliar sequences. Finally, the decreasing demand on visual
      working memory before familiar sequences suggests that sequence learning indeed
      develops from an attentive to an automatic phase.

PMID- 21094574
TI  - False recognition in Lewy-body disease and frontotemporal dementia.
AB  - The primary goal of this study was to evaluate the false recognition phenomenon
      in persons with frontotemporal dementia (FTD) and those with Lewy-body disease
      (LBD). Patients with LBD (n=10) or FTD (n=15) and their corresponding controls
      (n=30) were subjected to the Deese-Roediger-McDermott (DRM) paradigm to induce
      false recognition. Patients were first presented with items semantically related
      to a nonpresented critical target. The critical target was later included in a
      word list shown to patients to assess level of recognition. Both groups of
      patients showed a reduced level of false recognition of the critical target when
      controlling for their overall level of false alarms. This reduction was greater
      in persons with LBD than in those with FTD. Correlational analyses of performance
      on neuropsychological tests and the DRM variables indicated that the reduced DRM
      effect was associated with inhibition deficits in patients with LBD and with
      inhibition deficits and verbal memory in those with FTD. Our results support
      current models suggesting that these cognitive components contribute to the false
      recognition effect.

PMID- 21094575
TI  - Behavioral performances in participants with phonological dyslexia and different
      patterns on the N170 component.
AB  - Adults with phonological dyslexia and controls performed a lexical decision task
      while ERPs were recorded in the occipitotemporal pathway. Based on N170
      durations, two subgroups were formed: dysl1 showing longer N170 durations and
      dysl2 showing normal N170 durations. While the dysl1 subgroup had poorer accuracy
      for infrequent words and pseudo-words, the dysl2 group responded more slowly than
      controls to pseudo-words. N170 amplitudes were larger in the left hemisphere for
      controls irrespective of items. In the dysl1 subgroup, N170 amplitudes were
      larger in the left hemisphere than the right for words but not for pseudo-words,
      a sign of hemispheric compensation, while in the dysl2 subgroup signs of
      bilateralization were observed. Moreover, in the dysl1 subgroup, P100 amplitudes
      were smaller than controls. These results indicate different behavioral profiles
      of dyslexics with different patterns of P100 and N170 components. The ERP changes
      may be due to different behavioral strategies employed by each subgroup,
      logographic in dysl2 and phonological in dysl1.

PMID- 21094576
TI  - [Breast repaired by silicone implant. Case report of necrobiosis lipoidica].
AB  - The authors report a very rare case of necrobiosis lipoidica, histopathologically
      confirmed, which happened in the breast a few months following the insertion of a
      silicone implant (post-mastectomy reconstruction). This case raises two problems:
      the physiopathology (role of the silicone implant) and the treatment of this
      accident, resistant to current therapy.

PMID- 21094577
TI  - Primary or secondary laparoscopy for staging in patients with uterine sarcoma.

PMID- 21094578
TI  - Regulation by hypoxia of adrenomedullin output and expression in human
      trophoblast cells.
AB  - OBJECTIVES: Plasma adrenomedullin concentrations are increased in the fetal
      circulation in acute and chronic hypoxic conditions. The effect of hypoxia in
      regulating adrenomedullin synthesis and secretion was investigated in human
      placental trophoblast cells. STUDY DESIGN: Human trophoblast cells obtained from
      term placentas (n = 7) were cultured in hypoxic condition (3% oxygen).
      Cytotrophoblast cells were cultured for up to 48 h and syncytiotrophoblasts for
      2, 8 and 24 h. Changes in adrenomedullin output compared to normoxic conditions
      were measured by radioimmunoassay. Protein expression was evaluated with Western
      blot and immunocytochemistry. RESULTS: Hypoxia induced a time-dependent increase
      in adrenomedullin output and protein expression by placental trophoblast cells.
      CONCLUSIONS: Hypoxia regulates adrenomedullin secretion and expression by human
      placenta, thereby promoting increased adrenomedullin concentration in the fetal
      circulation in clinical circumstances characterized by reduced oxygen levels.

PMID- 21094579
TI  - Source characterization of nervous system active pharmaceutical ingredients in
      healthcare facility wastewaters.
AB  - Nervous system active pharmaceutical ingredients (APIs), including anti
      depressants and opioids, are important clinically administered pharmaceuticals
      within healthcare facilities. This study provides source characterization data
      describing the composition and magnitude of nervous system APIs present in
      healthcare facility wastewaters. Concentrations and mass loadings of ten nervous
      system APIs and three nervous system API metabolites are reported for wastewaters
      from a hospital, nursing, assisted living, and independent living facility within
      a single municipality. Concentrations of nervous system APIs ranged from non
      detectable levels for alprazolam in all four facility wastewaters to a high of
      290 ng/L amitriptyline in nursing facility wastewater. The summed mean
      concentration of all thirteen analytes ranged from 402 ng/L in independent living
      facility wastewater to 624 ng/L in assisted living facility wastewater.
      Wastewater flow rates from each facility were combined with concentration data to
      estimate the daily mass loading of nervous system APIs leaving each facility
      through wastewater discharge to the municipal sewer system. The total mass
      loading of all thirteen analytes for the hospital, nursing, assisted living, and
      independent living facility was 228, 44, 29.5, and 28.1 mg/day, respectively. The
      total mass loading of nervous system APIs contributed to the municipality's
      wastewater from all four facilities was 330 mg/day.

PMID- 21094580
TI  - For wider acceptance of radical cystectomy and extended pelvic lymphadenectomy.

PMID- 21094581
TI  - Cortical visual evoked potentials recorded after optic tract near field
      stimulation during GPi-DBS in non-cooperative patients.
AB  - OBJECT: Neurophysiologic monitoring during deep brain stimulation (DBS)
      interventions in the globus pallidus internum (Gpi) for the treatment of
      Parkinson's disease or primary dystonia is generally based upon microelectrode
      recordings (MER); moreover, MER request sophisticated technology and high level
      trained personnel for a reliable monitoring. Recordings of cortical visual evoked
      potentials (CVEPs) obtained after stimulation of the optic tract may be a
      potential option to MER; since optic tract lies just beneath the best target for
      Gpi DBS, changes in CVEPs during intraoperative exploration may drive a correct
      electrode positioning. PATIENTS AND METHODS: Cortical VEPs from optic tract
      stimulation (OT C-CEPs) have been recorded in seven patients during GPi-DBS for
      the treatment of Parkinson's disease and primary dystonia under general sedation.
      OT C-VEPs were obtained after near-field monopolar stimulation of the optic
      tract; recording electrodes were at the scalp. Cortical responses after optic
      tract versus standard visual stimulation were compared. RESULTS: After
      intraoperative near-field OT stimulation a biphasic wave, named N40-P70, was
      detected in all cases. N40-P70 neither change in morphology nor in latency at
      different depths, but increased in amplitude approaching the optic tract. The
      electrode tip was positioned just 1mm above the point where OT-CVEPs showed the
      larger amplitude. No MERs were obtained in these patients; OT CVEPs were the only
      method to detect the Gpi before positioning the electrodes. CONCLUSIONS: OT CVEPs
      seem to be as reliable as MER to detail the optimal target in Gpi surgery: in
      addition they are less expensive, faster to perform and easier to decode.

PMID- 21094582
TI  - Elevated leukocyte count in asymptomatic subjects is associated with a higher
      risk for cerebral white matter lesions.
AB  - OBJECTIVE: Cerebral white matter lesions (WMLs) are radiologic markers of small
      vessel disease in brain, and inflammatory processes were related to WMLs. We
      propose to determine if elevated leukocyte count was associated with a higher
      risk of WMLs. METHODS: 1586 asymptomatic subjects who visited our hospital for a
      routine health check-up were enrolled. Leukocyte counts were measured and the
      presence of moderate to severe WMLs was determined by brain MRI. RESULTS: Thirty
      (1.9%) had moderate to severe WMLs, and a significant greater proportion (4.1%)
      of subjects in the highest leukocyte count quartile had moderate to severe WMLs.
      After adjusting by C-reactive protein, aspirin use and cardiovascular risk
      factors, the highest quartile of leukocyte count (>=6.7*109/L) was significantly
      associated with moderate to severe WMLs compared with the lowest quartile
      [adjusted odds ratio, 4.03; 95% confidence interval, 1.05-15.5]. CONCLUSION: The
      authors report for the first time that an elevated leukocyte count is
      independently associated with moderate to severe WMLs.

PMID- 21094583
TI  - Isolation and characterization of human lung cancer antigens by serological
      screening with autologous antibodies.
AB  - Serological analysis of a recombinant cDNA expression library (SEREX) derived
      from two lung adenocarcinoma cancer cell lines using autologous sera led to the
      isolation of 41 positive cDNA clones comprising 28 different antigens. They coded
      for a variety of nuclear and cytoplasmic proteins. Among the antigens,
      nucleoporin 107 (NUP107) was isolated most frequently (5 of 41 clones). The
      second most frequently isolated antigen was coded for by C21orf58 (4 of 41
      clones). During serological analysis of selected antigens based on their
      reactivity to sera from normal individuals and lung cancer patients, none of the
      antigens showed a cancer-restricted recognition pattern. However, five genes
      including NUP107 showed higher expression when we examined the changes in gene
      expression in five different adenocarcinoma cell lines, including those used in
      SEREX, compared with their levels in normal lung tissues by cDNA microarray
      analysis. On the other hand, the expression levels of five genes including
      C21orf58 were down regulated in all adenocarcinoma cell lines. This SEREX study
      combining comprehensive gene expression assays has added to the growing list of
      lung cancer antigens, which may aid the development of diagnostic and
      immunotherapeutic reagents for patients with lung cancer.

PMID- 21094584
TI  - Experimental infection of dogs (Canis familiaris) with sporulated oocysts of
      Neospora caninum.
AB  - Neospora caninum is widely distributed in the world and this parasite is one of
      the major causes of abortion in cattle. Dogs and coyotes are definitive hosts of
      N. caninum and several species of domestic and wild animals are intermediate
      hosts. Dogs can become infected by the ingestion of tissues containing cysts and
      then excrete oocysts. It is not yet known whether sporulated oocysts are able to
      induce a patent infection in dogs, i.e. a shedding of N. caninum oocysts in
      feces. The objective of this study was to experimentally examine the infection of
      dogs by sporulated oocysts. The oocysts used in the experiment were obtained by
      feeding dogs with brain of buffaloes (Bubalus bubalis) positive for anti-N.
      caninum antibodies by indirect fluorescent antibody test (IFAT >=200). Oocysts
      shed by these dogs were confirmed to be N. caninum by molecular methods and by
      bioassay in gerbils, and sporulated N. caninum oocysts were used for the oral
      infection of four dogs. The dogs were 8 weeks old and negative for antibodies to
      N. caninum and Toxoplasma gondii. Dogs 1 and 4 received an inoculum of 10,000
      sporulated oocysts each; dog 2 an inoculum of 5000 sporulated oocysts and dog 3
      received 1000 sporulated oocysts of N. caninum. The total feces excreted by these
      dogs were collected and examined daily for a period of 30 days. No oocysts were
      found in their feces. The dogs were monitored monthly for a 6-month period to
      observe a possible seroconversion and when this occurred the animals were
      eliminated from the experiment. Dogs 1 and 4 seroconverted 1 month after the
      infection with titer, in the IFAT, of 1600 and 800, respectively; the other two
      dogs presented no seroconvertion during the 6-month period. Dogs 1 and 2 were
      euthanized 180 days after infection and were examined for the detection of N.
      caninum in tissues (brain, muscle, lymph node, liver, lung, heart and bone
      marrow) by immunohistochemistry and PCR with negative results in both techniques.
      Bioassay in gerbils with brain of these dogs was also performed and again the
      results were negative. In conclusion, dogs infected with sporulated oocysts of N.
      caninum were not able to shed oocysts in feces. However, a higher dose of
      infection stimulated the production of antibodies against N. caninum in the dogs.

PMID- 21094585
TI  - Contextual profiles of young adult ecstasy users: A multisite study.
AB  - These analyses assess contextual profiles of 612 young adult ecstasy users, 18-30
      years of age, from St. Louis (USA), Miami (USA) and Sydney (Australia). Bivariate
      analyses revealed different contextual factors influencing ecstasy use. Friends
      were the most common sources of ecstasy at all sites and most used with friends.
      St. Louis and Miami use mostly occurred in residences, whereas in Sydney use was
      mostly at clubs, bars or restaurants. Ecstasy consumption at public places and in
      cars, trains or ferries was significantly higher in Miami (89% and 77%) than in
      St. Louis (67% and 65%) and Sydney (67% and 61%). At all sites, simultaneous use
      of LSD/mushroom and nitrous oxide with ecstasy was common; concurrent
      amphetamines predominated in Sydney and heroin/opiates in St. Louis Contextual
      factors influencing ecstasy use among young adults vary by geographic region.
      Their inclusion may help tailor effective prevention programs to reduce or
      ameliorate ecstasy use.

PMID- 21094586
TI  - Utility of real-time diagnosis using contact endoscopy for oral and lingual
      diseases.
AB  - OBJECTIVE: In this study, we prospectively investigated the diagnostic accuracy
      of CE findings in oral and lingual diseases. METHODS: Between January 2004 and
      December 2009, CE was used to examine 66 patients with oral and lingual diseases
      at Hyogo College of Medicine Hospital. Blood vessel networks and superficial cell
      layers in the mucosal epithelium of normal and lesion sites were observed after
      staining with 1% methylene blue. Endoscopic diagnoses (CE diagnosis) were
      compared with subsequent definitive diagnoses based on pathological findings. The
      sensitivity and specificity for CE diagnosis were calculated. RESULTS: On CE
      findings, SCC showed the characteristics of absent and tortuous blood vessels,
      heterogeneous distribution, and increased nucleus/cytoplasm (N/C) ratio.
      Leukoplakia showed no atypical cells, abundant cornified layers, or cytoplasm
      without nuclei. Lesions were pathologically classified into three groups: 46
      squamous cell carcinomas (SCC), 10 leukoplakias, and 10 other benign lesions
      (n=66). In 4 patients with SCC, malignancy was underestimated by CE findings. The
      overall diagnostic rate of the CE was 93.9% (62/66 patients). The sensitivity and
      specificity of SCC were 0.913 (42/46 patients) and 1.0 (20/20 patients),
      respectively. CONCLUSION: The usefulness of contact endoscopy (CE) as an in vivo
      real-time diagnostic instrument that can deliver results prior to pathological
      confirmation was suggested.

PMID- 21094587
TI  - Hereditary progressive dystonia with marked diurnal fluctuation.
AB  - Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a dopa
      responsive dystonia, now called autosomal dominant GTP cyclohydrolase 1
      deficiency or Segawa disease, caused by mutation of the GCH-1 gene located on
      14q22.1 to q22.2. Because of heterozygous mutation, partial deficiency of
      tetrahydrobiopterin affects tyrosine hydroxylase (TH) rather selectively and
      causes decrease of TH in the terminals of the nigrostriatal dopamine (NS DA)
      neurons, projecting to the D1 receptors on the striosome, the striatal direct
      pathways and the subthalamic nucleus (STN) and the D4 receptors of the
      tuberoinfundibular tract. The activities of TH in the terminal are high in early
      childhood decrease exponentially to the stational level around early twenties,
      and show circadian oscillatron. TH in HPD follows these variations with around
      20% of normal levels and with development of the downstream structures show
      appears characteristic clinical symptoms age dependently. In late fetus period to
      early infancy, through the striosome-substantia nigra pars compacta pathway
      failure in morphogenesis of the DA neurons in substantia nigra, in childhood
      around 6 years postural dystonia through the D1 direct pathways and the
      descending output of the basal ganglia. Diurnal fluctuation is apparent in
      childhood but decrease its grade with age. TH deficiency at the terminal on the
      STN causes action dystonia from around 8 years and postural tremor from around 10
      years, focal dystonia in adulthood. Adult onset cases in the family with action
      dystonia start with writer's cramp, torticollis or generalized rigid hypertonus
      with tremor but do not show postural dystonia. TH deficiency on the D4 receptors
      causes stagnation of the body length in childhood. With or without action
      dystonia depends on the locus of mutation. Postural dystonia is inhibitory
      disorder, while action dystonia is excitatory disorder. The TH deficiency at the
      terminal does not cause morphological changes or degenerative process. Thus,
      levodopa shows favorable effects without any relation to the duration of illness.

PMID- 21094588
TI  - Acute encephalopathy in two cases with severe congenital hydrocephalus.
AB  - We report acute encephalopathy in two cases with severe congenital hydrocephalus.
      Case 1 was a 23-month-old girl, born at of 36weeks gestation and delivered by
      cesarean section due to congenital hydrocephalus. Magnetic resonance imaging
      (MRI) showed prominent ventricular dilation associated with hydrocephalus, Dandy
      Walker variant and cortical malformation. The blood test for toxoplasmosis,
      syphilis, varicella-zoster, rubella, cytomegalovirus, and herpes simplex virus
      (TORCH) complex and various metabolic tests of blood and urine specimens yielded
      unremarkable results. She was admitted to our hospital for respiratory failure
      with fever and her clinical course deteriorated, progressing to hemiconvulsion
      hemiplegia epilepsy syndrome. Case 2 was a 17-month-old boy, born by spontaneous
      vertex delivery at 39weeks. Severe, asymmetrical ventricular dilation associated
      with hydrocephalus, cerebellar and brainstem hypoplasia, and punctuate
      calcifications of the thalamus, third and fourth ventricles, around the aqueduct,
      were observed on computed tomography (CT). The blood test for TORCH complex and
      various metabolic tests of blood and urine specimens yielded unremarkable
      results. He was admitted to our hospital for status epilepticus with fever and
      his clinical course progressed to hemorrhagic shock and encephalopathy syndrome.
      In patients with brain disorders, diagnosis and treatment are likely to be
      delayed and prognosis may thereby be worsened. When status epileptics or
      prolonged coma manifests even in patients with severe brain disorders, we must
      consider encephalopathy in the differential diagnosis.

PMID- 21094589
TI  - [Type 2 diabetes: increasing therapeutic progress and increasing cardiovascular
      deaths due to diabetes. So where's the problem?].

PMID- 21094590
TI  - Examination of standardized patient performance: accuracy and consistency of six
      standardized patients over time.
AB  - OBJECTIVE: To explore the accuracy and consistency of standardized patient (SP)
      performance in the context of routine genetic counseling, focusing on elements
      beyond scripted case items including general communication style and affective
      demeanor. METHODS: One hundred seventy-seven genetic counselors were randomly
      assigned to counsel one of six SPs. Videotapes and transcripts of the sessions
      were analyzed to assess consistency of performance across four dimensions.
      RESULTS: Accuracy of script item presentation was high; 91% and 89% in the
      prenatal and cancer cases. However, there were statistically significant
      differences among SPs in the accuracy of presentation, general communication
      style, and some aspects of affective presentation. All SPs were rated as
      presenting with similarly high levels of realism. SP performance over time was
      generally consistent, with some small but statistically significant differences.
      CONCLUSION AND PRACTICE IMPLICATIONS: These findings demonstrate that well
      trained SPs can not only perform the factual elements of a case with high degrees
      of accuracy and realism; but they can also maintain sufficient levels of
      uniformity in general communication style and affective demeanor over time to
      support their use in even the demanding context of genetic counseling. Results
      indicate a need for an additional focus in training on consistency between
      different SPs.

PMID- 21094591
TI  - Performance contracting to engage detoxification-only patients into continued
      rehabilitation.
AB  - In 2006, only 18.7% of Delaware's detoxification patients were admitted to
      continuing recovery-oriented treatment within 30 days after discharge. In
      response, Delaware established financial contingencies to (1) maintain 90%
      detoxification occupancy, (2) make receipt of 10% of the facility's monthly
      reimbursement contingent on 25% of patients entering treatment, and (3) provide a
      $500 bonus for every patient with three or more prior detoxification visits who
      was retained in treatment. Under the performance contract, the detoxification
      provider (1) maintained the 90% occupancy requirement, (2) achieved the 25%
      treatment entry target for 7 of 12 months, and (3) observed only 8% (27/337) of
      detoxification completions that met the targeted length of stay. Continuation to
      and retention in treatment was even more constrained for patients with three or
      more prior detoxifications. Contrary to the policy intent, the number of patients
      with three or more detoxifications in fiscal year (FY) 2008 is nearly triple that
      of FY 2006. The modest gain in the transition rate was achieved without changes
      in patient access; the FY 2008 patient population reported significantly higher
      rates of homelessness and a younger age of first use than before the performance
      contract in FY 2006. Performance contracting may offer promise for improving
      transition to treatment rates. However, the unique needs of detoxification
      patients, the treatment capacity of each level of care to meet patient needs, and
      the structure of the performance contract must be carefully considered.
      Performance contracting efforts may be strengthened when service contracts across
      the system are tightly synchronized.

PMID- 21094592
TI  - Acquisition of nonlinear forward optics in generative models: two-stage "downside
      up" learning for occluded vision.
AB  - We propose a two-stage learning method which implements occluded visual scene
      analysis into a generative model, a type of hierarchical neural network with bi
      directional synaptic connections. Here, top-down connections simulate forward
      optics to generate predictions for sensory driven low-level representation,
      whereas bottom-up connections function to send the prediction error, the
      difference between the sensory based and the predicted low-level representation,
      to higher areas. The prediction error is then used to update the high-level
      representation to obtain better agreement with the visual scene. Although the
      actual forward optics is highly nonlinear and the accuracy of simulated forward
      optics is crucial for these types of models, the majority of previous studies
      have only investigated linear and simplified cases of forward optics. Here we
      take occluded vision as an example of nonlinear forward optics, where an object
      in front completely masks out the object behind. We propose a two-staged learning
      method inspired by the staged development of infant visual capacity. In the
      primary learning stage, a minimal set of object basis is acquired within a linear
      generative model using the conventional unsupervised learning scheme. In the
      secondary learning stage, an auxiliary multi-layer neural network is trained to
      acquire nonlinear forward optics by supervised learning. The important point is
      that the high-level representation of the linear generative model serves as the
      input and the sensory driven low-level representation provides the desired
      output. Numerical simulations show that occluded visual scene analysis can indeed
      be implemented by the proposed method. Furthermore, considering the format of
      input to the multi-layer network and analysis of hidden-layer units leads to the
      prediction that whole object representation of partially occluded objects,
      together with complex intermediate representation as a consequence of nonlinear
      transformation from non-occluded to occluded representation may exist in the low
      level visual system of the brain.

PMID- 21094593
TI  - A single episode of neonatal seizures alters the cerebellum of immature rats.
AB  - PURPOSE: to test whether a single episode of early-life seizures may interfere
      with the development of the cerebellum. The cerebellum is particularly vulnerable
      in infants, since it is characterized by an important postnatal histogenesis that
      leads to the settling of adult circuitry. METHODS: seizures were induced in 10
      day-old Wistar rats with a single convulsive dose (80MUg/g b.w., s.c.) of
      pentylentetrazole (PTZ). Immediately after rats were treated with (3)H-thymidine
      ((3)HTdR, 2.5MUCi/g b.w, s.c.). Rats were killed 4h later and paraffin sections
      of the cerebellar vermis were processed for (3)HTdR autoradiography and
      immunocytochemistry for 2/3 subunits of AMPA glutamate receptor (GluR2/3),
      glutamate transporter 1 (GLT1) and calbindin. RESULTS: seizures reduced the
      proliferation rate of cells in the external germinal layer. Purkinje cells showed
      increased GluR2/3 immunoreactivity. However, some Purkinje cells were unstained
      or lost. Increased GLT1 immunoreactivity was present in glial cells surrounding
      Purkinje cells. Calbindin immunoreaction confirmed that some Purkinje cells were
      missed. The remaining Purkinje cells showed large spheroids along the course of
      their axon. CONCLUSIONS: data indicate that seizures lead to a loss and
      alteration of Purkinje cells in the cerebellum of immature rats. Since at 10 days
      of life Purkinje cells are no more proliferating, the loss of Purkinje cells
      should be permanent.

PMID- 21094594
TI  - The study of core-shell molecularly imprinted polymers of 17beta-estradiol on the
      surface of silica nanoparticles.
AB  - In this paper, highly selective core-shell molecularly imprinted polymers of
      17beta-estradiol on the surface of silica nanoparticles (SiO(2)@E2-MIPs) were
      prepared. The SiO(2)@E2-MIPs were characterized by Fourier transform infrared
      spectrometer (FT-IR), transmission electron microscope (TEM), dynamic adsorption
      and static adsorption tests. The sorption capacity of the SiO(2)@E2-MIPs were
      nearly 5 times that of the non-imprinted polymers (NIPs), and it only took 25 min
      to achieve the sorption equilibrium. It indicated that the SiO(2)@E2-MIPs
      exhibited a high selectivity, large adsorption capacity and fast kinetics. When
      the SiO(2)@E2-MIPs were used as dispersive solid-phase extraction (dSPE)
      absorbents to selectively enrich and determine estrogens in duck feed, the
      average recoveries of E2 and estriol (E3) were higher than 96.74% and 72.07%,
      respectively, and the relative standard deviations (RSD) of E2 and E3 were less
      than 1.61% and 3.28%, respectively. The study provides an effective method for
      the separation and enrichment of estrogens in the complex matrix samples by the
      SiO(2)@E2-MIPs.

PMID- 21094595
TI  - Simultaneous immobilization of glucose oxidase on the surface and cavity of
      hollow gold nanospheres as labels for highly sensitive electrochemical
      immunoassay of tumor marker.
AB  - A novel tracer, glucose oxidase (GOD)-functionalized hollow gold nanospheres
      encapsulating glucose oxidase (Au(shell)@GOD), was designed to label the
      ferrocenemonocarboxylic-grafted secondary antibodies (Fc@Ab(2)) for highly
      sensitive detection of tumor marker using carboxyl group functionalized multiwall
      carbon nanotubes as platform. Initially, Au(shell)@GOD was synthesized specially
      by reverse micelle approach, and then the labeling of antibody and the
      preparation of GOD-functionalized Au(shell)@GOD were performed by one-pot
      assembly of Fc@Ab(2) and GOD on the surface of Au(shell)@GOD. The ferrocene used
      to label antibodies acted as a mediator of electron transfer between GOD and
      electrode surface. The high-content glucose oxidase in the tracer (on the surface
      and in the cavity) could significantly amplify the amperometric signal for
      sandwich-type immunoassay. Using carcinoembryonic antigen (CEA) as model analyte,
      the designed tracer showed linear range from 0.02 to 5.0 ng mL(-1) with the
      detection limit down to 6.7 pg mL(-1). The assay results of serum samples with
      the proposed method were in an acceptable agreement with the reference values.
      The new protocol showed acceptable stability and reproducibility, high
      sensitivity, and good precision, which could provide a promising potential for
      clinical screening and diagnosis of tumor disease.

PMID- 21094596
TI  - Au-NPs enhanced SPR biosensor based on hairpin DNA without the effect of
      nonspecific adsorption.
AB  - Gold nanoparticles (Au-NPs) are usually used to amplify surface plasmon resonance
      (SPR) signals, however, the serious nonspecific adsorption has largely limited
      their practical applications. Here, we developed a novel Au-NPs enhanced
      biosensor without the effect of nonspecific adsorption: cutting Au-NPs off from
      the biosensor surface by RsaI endonuclease. In order to further improve the
      sensitivity, the probe DNA was designed specially. After the cleavage reaction,
      the residual probe DNA formed hairpin structure, which also resulted in a great
      change in SPR dip shift. Then, with the coaction of Au-NPs and conformation
      change of probe DNA, the SPR signal was amplified greatly. Using this method, we
      monitored the process of DNA cleavage in real-time and achieved a detection level
      of 5*10(-8) M. Moreover, the result of X-ray photoelectron spectroscopy (XPS)
      experiment further confirmed that large nonspecific adsorption existed. However,
      because SPR recorded a process in which the Au-NPs were cut off, the serious
      nonspecific adsorption did not affect the experimental result.

PMID- 21094597
TI  - A portable generic DNA bioassay system based on in situ oligonucleotide synthesis
      and hybridization detection.
AB  - In this study, we present a portable and generic DNA bioassay system based on in
      situ oligonucleotide synthesis followed by hybridization based detection. The
      system include two main parts, an oligonucleotide synthesizer and a fluorescence
      detection system. The oligonucleotide synthesizer is based on microfluidic
      technology and capable of synthesizing any desired oligonucleotide which can be
      either used as a primer for PCR based detection (external) or a probe for
      hybridization based detection (integrated) of a target DNA analyte. The
      oligonucleotide sequence can be remotely sent to the system. The integrated
      fluorescence detection system is based on a photodiode to detect Texas Red
      fluorophore as low as 0.5 fmol. The complete system, integrating the
      oligonucleotide synthesizer and fluorescence detection system, was successfully
      used to distinguish DNA from two different bacteria strains. The presented
      generic portable instrument has the potential to detect any desired DNA target
      sequence in the field. Potential applications are for homeland security and fast
      responses to emerging bio-threats.

PMID- 21094598
TI  - Structural biology of protein functional regulation.

PMID- 21094599
TI  - Biodegradation of chicken feathers waste directed by Bacillus subtilis
      recombinant cells: scaling up in a laboratory scale fermentor.
AB  - Biodegradation of chicken feathers waste directed by Bacillus subtilis DB 100
      (p5.2) cells was successfully carried out in 14L Bio Flo 110 laboratory scale
      fermentor. Seven liters of feathers-based modified basal medium II, feathers
      based tap water and feathers-based distilled water separately in the fermentor
      were inoculated with activated bacterial cells. The fermentation processes were
      conducted at 37 degrees C, 700 rpm agitation speed and 0.7 vvm air flow rate in
      the absence of kanamycin. Highest net levels of released feathers hydrolysis end
      products [soluble proteins and NH(2)-free amino groups] and keratinolytic
      alkaline protease activity in the fermentor were greatly comparable to those of
      shake flasks. Interestingly, the plasmid (p5.2) inside the recombinant B.
      subtilis cells growing in the fermentor displayed 100% stability till the fifth
      day of incubation and this presents a great challenge. Data certainly would
      encourage the transfer to larger scale fermentors to carry out feathers
      biodegradation process.

PMID- 21094600
TI  - Cloning and functional analysis of a new laccase gene from Trametes sp. 48424
      which had the high yield of laccase and strong ability for decolorizing different
      dyes.
AB  - The laccase gene lac48424-1 and its corresponding full-length cDNA were cloned
      and characterized from a novel white-rot fungi Trametes sp. 48424 which had the
      high yield of laccase and strong ability for decolorizing different dyes. The
      1563 bp full-length cDNA of lac48424-1 encoded a mature laccase protein
      containing 499 amino acids preceded by a signal peptide of 21 amino acids. The
      deduced protein sequence of LAC48424-1 showed high similarity with other known
      fungal laccases and contained four copper-binding conserved domains of typical
      laccase protein. The functionality of lac48424-1 gene encoding active laccase was
      verified by expressing the gene in the yeast Pichia pastoris successfully. It was
      found that the recombinant laccase produced by the yeast transformant could
      decolorize different dyes. The 5'-flanking sequence upstream of start codon was
      obtained by Self-Formed Adaptor PCR. Many putative cis-acting responsive elements
      involved in the transcriptional regulation were identified in the promoter region
      of lac48424-1.

PMID- 21094601
TI  - Pyrolysis of ramie residue: kinetic study and fuel gas produced in a cyclone
      furnace.
AB  - The thermal decomposition behavior of ramie residue (RR) and the characteristics
      of fuel gas produced in a cyclone furnace were studied. The pyrolysis kinetics
      was investigated using thermogravimetric analysis (TGA) at heating rates of 5-20
      degrees C/min. The results showed that RR mainly decomposed between 250 and 390
      degrees C, and the apparent activation energy ranged from 200 to 258 kJ/mol. In
      the cyclone furnace, fast pyrolysis, partial combustion and gasification occurred
      almost simultaneously, and the thermal energy was supplied by partial combustion
      of RR powder at the hypo stoichiometric amount of air. Higher effect of
      equivalence ratio (ER) led to higher reaction temperature and fewer contents of
      tar and char, but too high ER lowered fuel gas content and degraded fuel gas
      quality. Over the ranges of the experimental conditions, the gas yield varied
      between 1.07 and 2.08 N m(3)/kg and the LHV was between 3350 and 4798 kJ/Nm(3).

PMID- 21094602
TI  - Total recovery of nitrogen and phosphorus from three wetland plants by fast
      pyrolysis technology.
AB  - Fast pyrolysis of three wetland plants (Alligator weed, Oenanthe javanica and
      Typha angustifolia) in a vertical drop fixed bed reactor was investigated in this
      study. The experiments were carried out at different pyrolysis temperatures, and
      the maximum bio-oil yields achieved were 42.3%, 40.2% and 43.6% for Alligator
      weed, Oenanthe javanica and Typha angustifolia, respectively. The elemental
      composition of the bio-oil and char were analyzed, and the results show that a
      low temperature was appropriate for the nitrogen and phosphorus enrichment in
      char. GC-MS analysis shows that nitrogenous compounds, phenols and oxygenates
      were the main categories in the bio-oil. A series of leaching tests were carried
      out to examine the recovery of the nitrogen and phosphorus in the char, and the
      results indicate that significant fractions of nitrogen and phosphorus could be
      recovered by leaching process.

PMID- 21094603
TI  - Harvest of Scenedesmus sp. with bioflocculant and reuse of culture medium for
      subsequent high-density cultures.
AB  - The optimal flocculating conditions for harvesting high-density cultures of
      Scenedesmus sp. were investigated using inorganic coagulants and the
      bioflocculant produced by Paenibacillus polymyxa AM49. The flocculated medium as
      nutrients for subsequent algal cultivation was also tested. Consecutive treatment
      with 8.5 mM CaCl(2) and 0.2 mM FeCl(3) as coagulants and 1% bioflocculant from
      the culture broth of P. polymyxa AM49 showed the highest flocculating activity of
      up to 95% for high density algal cultures. The medium flocculated with the
      coagulants and bioflocculant showed less than 8% decrease in the growth yield in
      the subsequent algal cultivation. Furthermore, a 20% or 50% fresh BG11 medium
      supplement allowed the flocculated medium to maintain a high growth yield in
      subsequent algal cultivation. These results suggest that the flocculation method
      presented here is efficient and bio-friendly, and allows the reuse of the
      flocculated medium, thereby contributing to the economic cultivation and harvest
      of microalgae.

PMID- 21094605
TI  - Effects of cell entrapment on nucleic acid content and microbial diversity of
      mixed cultures in biological wastewater treatment.
AB  - The effects of entrapment on nucleic acid content and microbial diversity of
      mixed cultures in biological municipal wastewater treatment were investigated.
      Deoxyribonucleic acid content increased 1.6-5.5 times more in alginate entrapped
      cells than in free and polyvinyl alcohol (PVA) entrapped cells. PVA entrapment
      resulted in 1.1- to 5.9-fold more increases in ribonucleic acid content compared
      to that experienced by free and alginate entrapped cells. Entrapment in
      carrageenan changed the bacterial community structure more than the alginate and
      PVA entrapments (35-80% versus 0-35%) as determined by single-strand conformation
      polymorphism analyses. The change in the bacterial community structure of
      alginate entrapped cells was less time dependent than that of PVA entrapped
      cells. This study enhances understandings on the physiology of entrapped cells
      and their community evolution in wastewater treatment environments.

PMID- 21094604
TI  - Sorption of phosphate onto giant reed based adsorbent: FTIR, Raman spectrum
      analysis and dynamic sorption/desorption properties in filter bed.
AB  - A sorption process for the removal of phosphate was evaluated under various
      conditions using a filter bed packed with giant reed (GR) based adsorbent. FTIR
      spectrum measurement validated the existence of grafted amine groups in the
      adsorbent and Raman spectrum displayed the characteristic peaks of different
      forms of phosphate. The column sorption capacity of the adsorbent for phosphate
      was 54.67 mg g(-1) in comparison with the raw GR of 0.863 mg g(-1). Influent pH
      demonstrated an essential effect on the performance of the filter bed as compared
      to other influent conditions (flow rates and influent concentrations) and the
      optimal pH was selected at 5.0-10.0. Eluents of HCl, NaOH and NaCl solutions with
      concentrations of 0.01-0.1 mol l(-1) showed the excellent capacities for
      desorption of phosphate from the adsorbent, and their elution processes could be
      finished in 90 min.

PMID- 21094606
TI  - Discovery of isoindoline and tetrahydroisoquinoline derivatives as potent,
      selective PPARdelta agonists.
AB  - Small molecule isoindoline and tetrahydroisoquinoline derivatives have been
      identified as selective agonists of human peroxisome proliferator-activated
      receptor delta (PPARdelta. Compound 18 demonstrated efficacy in a biomarker for
      increased fatty acid oxidation, with upregulation of pyruvate dehydrogenase
      kinase, isozyme 4 (PDK4) in human primary myotubes.

PMID- 21094607
TI  - Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based
      approach--part 2.
AB  - Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a
      viable core for the development of potent and selective CDK inhibitors. As part
      of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the
      design and synthesis of potent and selective kinase inhibitors, we focused on a
      key regulator in the cell cycle progression, CHK1. Continued SAR development of
      the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction
      with previously disclosed SAR at the C3 and C7 positions, led to the discovery of
      potent and selective CHK1 inhibitors.

PMID- 21094608
TI  - Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based
      approach--part 1.
AB  - The synthesis and hit-to-lead SAR development of a pyrazolo[1,5-a]pyrimidine hit
      4 is described leading to a series of potent, selective CHK1 inhibitors such as
      compound 17r. In the Letter, the further utility of the pyrazolo[1,5-a]pyrimidine
      template for the development of potent, selective kinase inhibitors is detailed.

PMID- 21094609
TI  - The role of vision in obese and normal-weight children's gait control.
AB  - Previous research has suggested that perceptual-motor difficulties may account
      for obese children's lower motor competence; however, specific evidence is
      currently lacking. Therefore, this study examined the effect of altered visual
      conditions on spatiotemporal and kinematic gait parameters in obese versus normal
      weight children. Thirty-two obese and normal-weight children (11.2+/-1.5 years)
      walked barefoot on an instrumented walkway at constant self-selected speed during
      LIGHT and DARK conditions. Three-dimensional motion analysis was performed to
      calculate spatiotemporal parameters, as well as sagittal trunk segment and lower
      extremity joint angles at heel-strike and toe-off. Self-selected speed did not
      significantly differ between groups. In the DARK condition, all participants
      walked at a significantly slower speed, decreased stride length, and increased
      stride width. Without normal vision, obese children had a more pronounced
      increase in relative double support time compared to the normal-weight group,
      resulting in a significantly greater percentage of the gait cycle spent in
      stance. Walking in the DARK, both groups showed greater forward tilt of the trunk
      and restricted hip movement. All participants had increased knee flexion at heel
      strike, as well as decreased knee extension and ankle plantarflexion at toe-off
      in the DARK condition. The removal of normal vision affected obese children's
      temporal gait pattern to a larger extent than that of normal-weight peers.
      Results suggest an increased dependency on vision in obese children to control
      locomotion. Next to the mechanical problem of moving excess mass, a different
      coupling between perception and action appears to be governing obese children's
      motor coordination and control.

PMID- 21094610
TI  - Synthesis of novel 5-amino-thiazolo[4,5-d]pyrimidines as E. coli and S. aureus
      SecA inhibitors.
AB  - An efficient synthesis of a library of 5-amino-thiazolo[4,5-d]pyrimidines is
      reported. Regioselective displacements of chlorines, as well as regioselective
      diazotation reactions are described, which allow the introduction of structural
      diversity on the scaffold by consecutive reactions. Screening of this focused
      library led to the discovery of SecA inhibitors from Escherichia coli and
      Staphylococcus aureus.

PMID- 21094612
TI  - Evaluation of HPGe detector efficiency for point sources using virtual point
      detector model.
AB  - The concept of a virtual point detector (VPD) has been developed and validated in
      the past for Ge(Li) and HPGe detectors. In the present research, a new semi
      empirical equation involving photon energy and source-virtual point detector
      distance for the efficiency of point sources by HPGe detectors is introduced ,
      which is based on the VPD model. The calculated efficiencies for both coaxial and
      off-axis geometries by this equation are in good agreement with experimental
      data. The estimated uncertainties are less than 4%.

PMID- 21094611
TI  - Cytotoxicity of delta-tocotrienols from Kielmeyera coriacea against cancer cell
      lines.
AB  - In the search for new anti-cancer compounds, Brazilian Cerrado plant species have
      been investigated. The hexane root bark extract of Kielmeyera coriacea lead to a
      mixture of delta-tocotrienol (1) and its dimer (2). The structures of both
      compounds 1 and 2 were established based on detailed 1D and 2D NMR and EI-MS
      analyses. The cytotoxicity of the mixture was tested against four human tumor
      cell lines in the following cultures: MDA-MB-435 (melanoma), HCT-8 (colon), HL-60
      (leukemia), and SF-295 (glioblastoma), and displayed IC(50) values ranging from
      8.08 to 23.58MUg/mL. Additional assays were performed in order to investigate the
      mechanism of action of the mixture (1+2) against the human leukemia cell line HL
      60. The results suggested that the mixture suppressed leukemia growth and reduced
      cell survival, triggering both apoptosis and necrosis, depending on the
      concentration.

PMID- 21094613
TI  - Controlled silencing of 4-coumarate:CoA ligase alters lignocellulose composition
      without affecting stem growth.
AB  - Many bioenergy feedstocks are not easily converted to fermentable substrates due
      to of high proportions of lignin, which impedes the degradation of cell wall
      polysaccharides to fermentable sugars. To reduce lignin levels during plant
      growth, we generated transgenic Arabidopsis plants that contain a gene that
      confers inducible silencing of both 4CL1 and 4CL2 genes; these genes play a
      compensatory role in normal development of Arabidopsis, including in mechanisms
      of stem growth. To alter lignocellulose composition at specific times in plant
      development, genes were silenced at bolting, immature stages (5-7 cm high), and
      intermediate stages (10-15 cm high). The stems of induced plants at all stages of
      development exhibited increased cellulose content and reduced amounts of total
      lignin when compared with non-induced stems. Furthermore, treating plants at
      advanced stages of development (the immature and intermediate stages) had little
      impact on plant growth and development while plants treated at the bolting stage
      exhibited modest abnormal development. Our results suggest that it is possible to
      alter lignocellulose composition in plants without negative effects on plant
      growth.

PMID- 21094614
TI  - Conscious and unconscious discriminations between true and false memories.
AB  - When subjects give higher confidence or memory ratings to a test word in a
      recognition test, do they simply raise their criterion without making better
      discrimination, or do they raise both criterion and true discrimination between
      the studied words (SW) and the lures? Given that previous studies found subjects'
      false alarm responses to lures slower than to SW, and recognition latency
      inversely correlated with the confidence rating, can the latency difference
      between the lures and SW be accounted for by confidence or memory ratings? The
      present results showed that when subjects gave higher confidence or memory
      ratings, both their bias and sensitivity were raised, indicating that they could
      consciously distinguish the lures from the SW. However, a latency difference
      between true and false recognitions persisted after confidence and memory ratings
      were held constant, suggesting an unconscious source of discrimination between
      the two types of memory.

PMID- 21094615
TI  - The genetics of epilepsy--the past, the present and future.
AB  - A BRIEF HISTORY OF HUMAN GENETICS: Sixty years is an appropriate yardstick for
      many reasons, not least for the remarkable advances in medicine, public health,
      psychology and biological disciplines. Particularly relevant is the approaching
      60th anniversary of the discovery of the structure of DNA, which unlocked the
      driving force of nature and spawned a plethora of scientific discoveries and
      economic development through the Bitoech industry. Prior to 1953, and before
      Watson and Crick burst into the Cambridge pub with their eureka moment, it was
      known that chromosomes were important, the first principles of clinical
      cytogenetics were emerging and the rules of heritable traits were well-advanced,
      but without the basic framework or mechanism. Human Molecular Genetics arrived
      when the first mutations were linked to human disorders reflecting the advances
      in understanding the genetic code, assembly of protein building blocks and
      methodological advances in reading the physical code (all be it very difficult
      process at the time). Accelerated by the introduction of recombinant gene
      technology in the 1980s, and in conjunction with the development of linked
      genetic marker maps, the catalogue of genes associated with disease has risen
      exponentially with classical examples such as sickle cell disease, cystic
      fibrosis and Huntington's disease. The advances approached super-sonic dimensions
      when genes were found in Mendelian families, and mapping strategies were adopted
      using the variation map of the human genome (SNP's, di-nucleotide repeats), in
      addition to targeted candidate gene approaches aided by the significant database
      resources available to investigators. Super-sonic gave way to light-speed with
      the publication of the 3 billion letters of the genetic code which constitutes
      the human genome, followed quickly by genomes in plants, bacteria, pathogens,
      fruits and vegetables, and a menagerie of eukaryotic and prokaryotic animals,
      often representing model systems for genomic and pathophysiological research. In
      short don't blink or you'll miss the next revolution - too late, it's just
      happened!

PMID- 21094616
TI  - Drainage surgery followed by postoperative irrigation with gentian violet for
      prosthetic graft infection caused by methicillin-resistant Staphylococcus aureus.
AB  - INTRODUCTION: Infection of a prosthetic graft is still associated with
      considerable morbidity and mortality. Conventionally, this vascular complication
      is treated by excising the infected graft, although prosthetic graft preservation
      is possible in selected cases. REPORT: We report the successful treatment of
      prosthetic graft infection caused by methicillin-resistant Staphylococcus aureus
      (MRSA) in three patients, by performing drainage surgery with postoperative
      irrigation using gentian violet. DISCUSSION: The combination of drainage surgery
      and irrigation with gentian violet solution provides an alternative option to
      graft excision for prosthetic graft infection.

PMID- 21094617
TI  - Induction of fetal/embryonic globin gene expression depends on intact cell
      signaling in definitive erythroid cells.
AB  - OBJECTIVE: The induction of fetal hemoglobin during definitive erythropoiesis is
      a major therapeutic goal in beta-globin gene disorders. Butyrate induces fetal
      hemoglobin, and p38 phosphorylation has been implicated in this process. We
      studied p38 and the effect of its inhibitors in a physiologic primary cell model
      of fetal/embryonic globin gene induction during definitive erythropoiesis.
      METHODS: p38 phosphorylation was evaluated in a short-term culture of definitive
      erythroid precursor (EryD) cells following butyrate induction, absent prolonged
      exposure to cytokines. The impact of p38 inhibitors on embryonic/fetal globin
      gene induction by butyrate and on normal erythroid processes, including
      proliferation, differentiation, cell cycle occupancy, and RNA transcription, was
      also examined. RESULTS: p38 phosphorylation, maximal at harvest of murine fetal
      liver-derived EryD (FL EryD), when minimal embryonic/fetal globin gene expression
      is seen, is suppressed by EPO (as reported by others). Butyrate initially delays
      EPO-mediated suppression of p38 phosphorylation, but p38 phosphorylation
      thereafter, at 30 minutes to 48 hours, is equivalent and at low levels in EPO
      treated FL EryD, with or without butyrate. Inhibitors of p38, at 10-50 MUM,
      prevent butyrate-mediated induction of embryonic/fetal globin gene expression. We
      found that p38 inhibitors, which also disrupt non-p38 signaling pathways, perturb
      cell division, erythroid differentiation, transit through the cell cycle, and RNA
      transcription in primary EryD. CONCLUSION: p38 inhibitors interrupt normal
      erythropoiesis and the capacity for embryonic/fetal globin gene induction.
      However, p38 signaling is maximal in primary EryD at harvest, when embryonic
      globin genes are minimally expressed, and diminishes thereafter. We conclude that
      p38 inhibitors disrupt cellular pathways that are essential to butyrate-induced
      embryonic/fetal globin gene expression. However, levels of p38 phosphorylation
      are not coordinate with embryonic/fetal globin gene expression in EryD, and
      increased signaling through p38 may not be the sine qua non for embryonic/fetal
      globin gene induction.

PMID- 21094618
TI  - Chlamydial infection in cattle: the burden of proof?

PMID- 21094619
TI  - Mechanisms of dynamic mechanical allodynia and dysesthesia in patients with
      peripheral and central neuropathic pain.
AB  - Eighteen patients with peripheral neuropathic pain (PNeP) and seven patients with
      central post-stroke pain (CPSP) all suffering from dynamic mechanical allodynia
      (DMA) in a limb were studied. From recent research it is reasonable to suggest
      that A-beta fibres constitute the peripheral substrate for DMA in patients with
      PNeP. The pathophysiological basis for DMA in patients with CPSP is unknown. It
      is clinically observed that some patients with neuropathic pain report variable
      intensity of DMA and volunteer that the phenomenon at times is only an
      unpleasant, i.e., dysesthetic sensation. The pathophysiological basis for dynamic
      mechanical dysesthesia (DMD) has never been addressed. Based on the
      aforementioned clinical observations we aimed at investigating if DMA is the
      hyperbole of DMD both mediated by A-beta fibres in the periphery. A
      compression/ischemia-induced (differential) nerve block in conjunction with
      repeated quantitative sensory testing of A-delta and C-fibre function using cold
      and warm stimuli was used to assess which nerve fibre population that contributes
      to DMA and DMD, respectively. During the nerve block there was a transition of
      DMA to DMD in all patients with PNeP and in 3/7 patients with CPSP. The rest of
      the patients lost DMA without transition to DMD. The transition or loss of DMA
      without transition occurred early and concurrently in time during the block and
      was paralleled by a continuous impairment of mainly A-beta fibre function. We
      therefore suggest DMA to be the hyperbole of DMD, the difference being the number
      of mechanoreceptive fibres having access to the nociceptive system.

PMID- 21094620
TI  - Postnatal expression of the homeobox gene Prrxl1 (Drg11) is increased in
      inflammatory but not neuropathic pain.
AB  - The paired-type homeodomain transcription factor Prrxl1 (also known as Drg11) is
      a key regulator of the differentiation and survival of dorsal root ganglia (DRG)
      and spinal nociceptive neurons in pre- and perinatal stages. Prrxl1(-/-) mice
      exhibit abnormalities in DRG-spinal projections, defects in superficial dorsal
      horn structure and neurochemistry, and reduced nociceptive behaviour in several
      pain tests. Although a low expression of Prrxl1 persists in dorsal root ganglia
      beyond embryonic development, no data exist on its role in adult life. In this
      paper we evaluate whether DRG expression of Prrxl1 is affected both in
      inflammatory and neuropathic models of pain in adult mice. Ipsilateral versus
      contralateral relative expression of Prrxl1 in the DRG was compared in control
      and pain animals. The expression of Prrxl1 mRNA in mice with zymosan-induced
      peripheral inflammation presented a 3.06 +/- 0.71-fold-increase in ipsilateral
      ganglia, which was significantly different from the value observed in control
      animals. In contrast, a slight, non-statistically significant decrease was
      detected in the SNI model of neuropathy. Interestingly, the expression of the
      mRNA splice variant Prrxl1b was unchanged in both pain conditions.
      Immunohistochemical studies showed an increase in the number of Prrxl1-positive
      neurons in the inflammatory pain model, which belonged both in the peptidergic
      and non-peptidergic categories. Our present results point to a role for Prrxl1 in
      sensitization of nociceptive neurons upon inflammatory pain.

PMID- 21094621
TI  - Overexpression of adapted U1snRNA in patients' cells to correct a 5' splice site
      mutation in propionic acidemia.
AB  - Splicing defects account for 16% of the mutant alleles in the PCCA and PCCB
      genes, encoding both subunits of the propionyl-CoA carboxylase (PCC) enzyme,
      defective in propionic acidemia, one of the most frequent organic acidemias
      causing variable neurological impairment. Most of the splicing mutations
      identified affect the conserved 3' splice (3' ss) or 5' splice (5' ss) sites, the
      latter predictably through lowering the strength of base pairing with U1snRNA.
      Among the 5' ss mutations we have focused on the c.1209+3A>G (IVS13+3A>G)
      mutation in the PCCA gene, identified in four patients (three homozygous and one
      heterozygous) of common geographical origin and causing exon 13 skipping. To
      study the potential of splicing modulation to restore PCC function, we analyzed
      the effect of transient transfections in patients' cells with modified U1snRNA
      adapted to compensate the mutant change and other mismatches at different
      positions of the 5' ss. Using this strategy normal transcript could be
      efficiently recovered with the concomitant disappearance of the aberrant exon
      skipping transcript, as observed after standard RT-PCR and sequence analysis or
      using fluorescent primers and semiquantitative RT-PCR. Different efficiencies
      with up to 100% exon inclusion were observed depending on the transfection
      conditions and specifically on the adapted U1snRNA used, confirming previously
      reported dependencies between nucleotides at the 5' ss for its correct
      recognition by the spliceosome. The reversal of the splicing defect did not
      result in a significant increase in enzyme activity, suggesting other factors
      must be taken into account for the application of overexpression of splice
      factors such as U1 as therapeutic strategy for splice defects.

PMID- 21094622
TI  - New, fast and green procedure for the synthesis of gold nanoparticles based on
      sonocatalysis.
AB  - An easy, cheap and green synthetic route, using high-power ultrasounds and sodium
      citrate dihydrate as non-toxic reducing and stabilizer agent, produces gold
      nanoparticles in aqueous solution, and at ambient conditions. The time required
      for the synthesis is 5.5 min. The spherical nanoparticles obtained by this route
      show a homogeneous size distribution, within the range 5-17 nm, with an average
      diameter of 10+/-1 nm. Moreover, 90% of the particles have a diameter ranging
      from 7 to 13 nm, and their half-life is more than 30 days. The gold nanoparticles
      synthesized following this route are known as sononanoparticles. Gold
      sononanoparticles have been characterized by TEM and XRD and their stability has
      been studied by UV-Vis spectroscopy. Alternative experimental designs are
      compared to optimize the proposed synthesis procedure.

PMID- 21094623
TI  - Juvenile dystonia-parkinsonism and dementia caused by a novel ATP13A2 frameshift
      mutation.

PMID- 21094624
TI  - The validity of O'Sullivan's classification system (CS) for a sub-group of NS
      CLBP with motor control impairment (MCI): overview of a series of studies and
      review of the literature.
AB  - Chronic Low Back Pain (LBP) remains a common, recalcitrant and costly problem for
      the individual sufferer and for society. Effective treatments that reduce the
      social and economic burden have yet to be established for the majority of chronic
      LBP cases. Lack of evidence for specific interventions has been blamed on the
      heterogeneity of the chronic LBP population as well as a lack of a patient
      centred bio-psycho-social approach. This issue of heterogeneity has resulted in
      classification being considered the highest research priority in the area of
      chronic LBP. The potential for a 'wash-out effect' caused by the heterogeneity of
      the chronic LBP populations sampled for randomised controlled clinical trials
      (RCTs), has driven the need for classifying patients with nonspecific chronic
      LBP. A summary of a series of studies is outlined in this review paper. They
      represent a comprehensive investigation into the validity of O'Sullivan's
      proposed mechanism-based classification system (CS) for a sub-group of localized
      mechanically provoked nonspecific chronic LBP with motor control impairment
      (MCI). Further, the findings of these studies are discussed in relation to the
      relevant literature and the clinical implications arising are presented. Finally,
      the limitations of this research are outlined and recommendations for future
      research are made.

PMID- 21094625
TI  - A unique HAV strain circulated in patients with acute HAV infection with
      different risk exposures in Tuscany, Italy.
AB  - BACKGROUND: Acute Hepatitis A Virus (HAV) is reported to be an emergent problem
      in several developed countries. OBJECTIVES AND STUDY DESIGN: The aim of this
      study was to analyse the HAV strains circulating among individuals with acute HAV
      infection, apparently transmitted by different routes, in several districts of
      Tuscany in central Italy, during the year 2008. RESULTS: An outbreak of acute HAV
      infection occurred from May to August 2008 in Arezzo; 32 individuals were
      admitted to the hospital, in 25 of them at least a linkage with an infected food
      handler and/or household contacts was reported and in 3 homosexuality was a
      possible risk factor. In Florence, from January 2008 to August 2008, 41
      individuals mainly homosexual men were admitted to two hospitals with the
      diagnosis of acute HAV. The phylogenetic analysis of VP1/2A region of HAV was
      used to characterize these HAV isolates. All viral sequences were assigned to
      genotype IA. All clustered in the same branch (bootstrap 82%) of phylogenetic
      tree, thus indicating the same circulating isolate. Apart of one isolate from
      France and one from Germany which were similar with the "Tuscany" strain reported
      here, high heterogeneity with the other European HAV strains reported in the
      GenBank in the last years, was observed. CONCLUSION: The detection of a unique
      HAV isolate circulating in different Tuscany districts, suggests sequential
      transmission of HAV infection in this geographical area through possible links
      among acute hepatitis cases. The application of safe food handling practices and
      vaccination of homosexual men may contribute to the prevention of HAV infection.

PMID- 21094626
TI  - Effectiveness of the computer enhanced visual learning method in teaching the
      society for fetal urology hydronephrosis grading system for urology trainees.
AB  - OBJECTIVE: A novel educational tool, Computer Enhanced Visual Learning (CEVL),
      has been used to improve resident performance of routine orchiopexy. Our
      objective was to assess the effect of a CEVL teaching module on the diagnostic
      accuracy of medical trainees in grading neonatal hydronephrosis on ultrasound
      using the Society for Fetal Urology (SFU) grading system. METHODS: The authors
      designed an online-based computerized tutorial to teach the grading of
      hydronephrosis using multimedia, practice cases and a grading checklist. In a
      crossover design trial, 29 residents and medical students were asked to grade 16
      standard neonatal renal ultrasounds using the SFU grading system before and after
      viewing the web-based e-learning module. Primary outcome was percent improvement
      in grading accuracy. RESULTS: The mean percentages of ultrasounds that were
      graded correctly before and after CEVL intervention were 51% and 72% respectively
      (mean improvement 21%, 95% CI 3-13%, P < 0.001). Residents graded correctly 56%
      of ultrasounds before and 74% after CEVL (mean 18%, 7-28%, P = 0.002). Medical
      students graded correctly 37% before and 69% after CEVL (mean improvement 32%,
      95% CI 16-48%, P = 0.002). CONCLUSION: Exposure to a computer-based learning
      module based on the CEVL platform improved urology residents' and medical
      students' correct assignment of SFU hydronephrosis grading to newborn renal
      ultrasounds.

PMID- 21094628
TI  - Comment on: Laparoscopic repeat sleeve gastrectomy versus duodenal switch after
      isolated sleeve gastrectomy for obesity.

PMID- 21094627
TI  - Phosphatidylserine reduces immune response against human recombinant Factor VIII
      in Hemophilia A mice by regulation of dendritic cell function.
AB  - A major clinical complication in the treatment of Hemophilia A using exogenously
      administered recombinant Factor VIII (FVIII) is the development of neutralizing
      antibodies. It has been shown previously that FVIII complexed with
      phosphatidylserine (PS) reduces the development of total and neutralizing
      antibody titers in hemophilic mice. The effect of complexation of FVIII with PS
      upon dendritic cell (DC) uptake, maturation and processing, T-cell proliferation
      and cytokine secretion profiles was investigated. Flow cytometric studies of DC
      showed that PS inhibited the up-regulation of cell surface co-stimulatory markers
      (CD86 and CD40). PS reduced T-cell proliferation and significantly increased
      levels of TGF-beta and IL-10 but reduced secretion of IL-6 and IL-17 compared to
      controls. The data suggest that PS reduces immunogenicity of FVIII by regulating
      dendritic cell maturation and subsequent T-lymphocyte activity through modulation
      of cytokine secretion. A possible mechanism for PS-mediated induction of FVIII
      tolerance is discussed.

PMID- 21094629
TI  - High factor XI, recurrent pregnancy loss, enoxaparin.
AB  - Of the 149 women with 0 pregnancy losses, 7 (5%) had factor XI level >=150%
      versus 5 of 31 (16%) women with recurrent pregnancy loss. Three of the 5 women
      with high factor XI and recurrent pregnancy loss, with 19 previous pregnancy
      losses and 0 live births, were given enoxaparin during 5 subsequent pregnancies,
      and had 6 term live births and 1 miscarriage.

PMID- 21094630
TI  - (14)C radiolabeling of proteins to monitor biodistribution of ingested proteins.
AB  - The economical preparation of microgram quantities of (14)C-labeled proteins by
      in vacuo methylation with methyl iodide is described. The (14)C radiolabeling was
      achieved by the covalent attachment of [(14)C]methyl groups onto amino and
      imidazole groups by reaction in vacuo with [(14)C]methyl iodide. The method was
      tested by investigating the biodistribution of (14)C in rats that were fed (14)C
      labeled human soluble cluster of differentiation 14 (CD14) protein, a receptor
      for bacterial lipopolysaccharide. Two other control proteins, bovine serum
      albumin (BSA) and casein, were also labeled with (14)C and used for comparative
      analysis to determine the following: (i) the efficacy and cost efficiency of the
      in vacuo radiolabeling procedure and (ii) the extent of incorporation of the
      (14)C label into the organs of orogastrically fed 10-day-old Sprague-Dawley rats.
      [(14)C]BSA, [(14)C]casein, and [(14)C]CD14 were individually prepared with
      specific radioactivities of 34,400, 18,800, and 163,000 disintegrations per
      minute (dpm)/microg, respectively. It was found that the accumulation of (14)C
      label in the organs of [(14)C]CD14-fed rats, most notably the persistence of
      (14)C in the stomach 480 min postgavage, was temporally and spatially distinct
      from [(14)C]BSA and [(14)C]casein-fed rats.

PMID- 21094631
TI  - Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent
      enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana.
AB  - Formation of the methylenedioxy bridge is an integral step in the biosynthesis of
      benzo[c]phenanthridine and protoberberine alkaloids in the Papaveraceae family of
      plants. This reaction in plants is catalyzed by cytochrome P450-dependent
      enzymes. Two cDNAs that encode cytochrome P450 enzymes belonging to the CYP719
      family were identified upon interrogation of an EST dataset prepared from 2-month
      old plantlets of the Mexican prickly poppy Argemone mexicana that accumulated the
      benzo[c]phenanthridine alkaloid sanguinarine and the protoberberine alkaloid
      berberine. CYP719A13 and CYP719A14 are 58% identical to each other and 77% and
      60% identical, respectively, to stylopine synthase CYP719A2 of
      benzo[c]phenanthridine biosynthesis in Eschscholzia californica. Functional
      heterologous expression of CYP719A14 and CYP719A13 in Spodoptera frugiperda Sf9
      cells produced recombinant enzymes that catalyzed the formation of the
      methylenedioxy bridge of (S)-cheilanthifoline from (S)-scoulerine and of (S)
      stylopine from (S)-cheilanthifoline, respectively. Twenty-seven potential
      substrates were tested with each enzyme. Whereas CYP719A14 transformed only (S)
      scoulerine to (S)-cheilanthifoline (K(m) 1.9+/-0.3; k(cat)/K(m) 1.7), CYP719A13
      converted (S)-tetrahydrocolumbamine to (S)-canadine (K(m) 2.7+/-1.3; k(cat)/K(m)
      12.8), (S)-cheilanthifoline to (S)-stylopine (K(m) 5.2+/-3.0; k(cat)/K(m) 2.6)
      and (S)-scoulerine to (S)-nandinine (K(m) 8.1+/-1.9; k(cat)/K(m) 0.7). These
      results indicate that although CYP719A14 participates in only sanguinarine
      biosynthesis, CYP719A13 can be involved in both sanguinarine and berberine
      formation in A. mexicana.

PMID- 21094632
TI  - Cyclic mechanical stretch reduces myofibroblast differentiation of primary lung
      fibroblasts.
AB  - In lung fibrosis tissue architecture and function is severely hampered by
      myofibroblasts due to excessive deposition of extracellular matrix and tissue
      contraction. Myofibroblasts differentiate from fibroblasts under the influence of
      transforming growth factor (TGF) beta(1) but this process is also controlled
      mechanically by cytoskeletal tension. In healthy lungs, the cytoskeleton of
      fibroblasts is mechanically strained during breathing. In stiffer fibrotic lung
      tissue, this mechanical stimulus is reduced, which may influence fibroblast-to
      myofibroblast differentiation. Therefore, we investigated the effect of cyclic
      mechanical stretch on fibroblast-to-myofibroblast differentiation. Primary normal
      human lung fibroblasts were grown on BioFlex culture plates and stimulated to
      undergo myofibroblast differentiation by 10 ng/ml TGFbeta(1). Cells were either
      or not subjected to cyclic mechanical stretch (sinusoidal pattern, maximum
      elongation 10%, 0.2 Hz) for a period of 48 h on a Flexercell apparatus. mRNA
      expression was analyzed by real-time PCR. Cyclic mechanical loading reduced the
      mRNA expression of the myofibroblast marker alpha-smooth muscle actin and the
      extracellular matrix proteins type-I, type-III, and type-V collagen, and tenascin
      C. These outcomes indicate that fibroblast-to-myofibroblast differentiation is
      reduced. Cyclic mechanical loading did not change the expression of the
      fibronectin ED-A splice variant, but did decrease the paracrine expression of
      TGFbeta(1), thereby suggesting a possible regulation mechanism for the observed
      effects. The data suggest that cyclic loading experienced by healthy lung cells
      during breathing may prevent fibroblasts from differentiating towards
      myofibroblasts.

PMID- 21094633
TI  - Regulated expression of acyl-CoA thioesterases in the differentiation of cultured
      rat brown adipocytes.
AB  - Acyl-CoA thioesterases (ACOTs) are enzymes that catalyze the hydrolysis of fatty
      acyl-CoAs to free fatty acids and CoA-SH. In this study, we show that the
      expression profile of the ACOT isoforms changes remarkably during the
      differentiation of cultured rat brown adipocytes. Immunocytochemistry suggested
      that cytosolic ACOT1 was present in the preadipocytes, while mitochondrial ACOT2
      was additionally expressed as the cells differentiated, concurrent with the
      accumulation of lipid droplets in the cytoplasm. Western blotting confirmed that,
      in contrast to ACOT1, the ACOT2 expression level was very low in the
      preadipocytes. However, after differentiation, the ACOT1 level fell to one-half
      of the baseline level and ACOT2 increased 18-fold. ACOT2 expression in the
      differentiated adipocytes was further enhanced by treatment with lipids or
      troglitazone. These changes in the ACOT2 expression level correlated well with
      changes in the expression of carnitine palmitoyltransferase 2, a mitochondrial
      beta-oxidation enzyme. These results indicate that, in differentiating brown
      adipocytes, cytosolic ACOT1 becomes downregulated as the cellular use of acyl-CoA
      increases, while mitochondrial ACOT2 is upregulated as the beta-oxidation
      capacity increases. ACOT isoform expression may be regulated during brown
      adipocyte differentiation to support the fat storage and combustion
      characteristics of this cell type.

PMID- 21094634
TI  - High density lipoprotein downregulates angiotensin II type 1 receptor and
      inhibits angiotensin II-induced cardiac hypertrophy.
AB  - Angiotensin II (AngII) and its type receptor (AT1-R) play important roles in the
      development of cardiac hypertrophy. Low level of high density lipoprotein (HDL)
      is also an independent risk factor for cardiac hypertrophy. We therefore
      investigated in the present study whether HDL inhibits cardiac hypertrophy
      relatively to inhibition of AngII and AT1-R in both in vitro and in vivo
      experiments. Stimulation of cultured cardiomyocytes of neonatal rats with AngII
      for 24 h and infusion of AngII in mice for 2 weeks resulted in marked cardiac
      hypertrophic responses including increased protein synthesis, enlarged sizes of
      cardiomyocytes and hearts, upregulated phosphorylation levels of protein kinases
      and reprogrammed expression of specific genes, all of which were significantly
      attenuated by the treatment with HDL. Furthermore, AngII-treatment induced
      upregulation of AT-R expression either in cultured cardiomyocytes or in hearts of
      mice and HDL significantly suppressed the upregulation of AT1-R. Our results
      suggest that HDL may abrogate AngII-induced cardiac hypertrophy through
      downregulation of AT1-R expression.

PMID- 21094635
TI  - Differences in islet-enriched miRNAs in healthy and glucose intolerant human
      subjects.
AB  - Many microRNAs (miRNAs) are known to be cell-type specific and are implicated in
      development of diseases. We investigated the global expression pattern of miRNAs
      in human pancreatic islets compared to liver and skeletal muscle, using bead
      based technology and quantitative RT-PCR. In addition to the known islet-specific
      miR-375, we also found enrichment of miR-127-3p, miR-184, miR-195 and miR-493* in
      the pancreatic islets. The expression of miR-375, miR-127-3p, miR-184 and the
      liver-enriched miR-122 is positively correlated to insulin biosynthesis, while
      the expression of miR-127-3p and miR-184 is negatively correlated to glucose
      stimulated insulin secretion (GSIS). These correlations were absent in islets of
      glucose intolerant donors (HbA1c >= 6.1). We suggest that the presence of an
      islet-specific miRNA network, which consists of at least miR-375, miR-127-3p and
      miR-184, potentially involved in insulin secretion. Our results provide new
      insight into miRNA-mediated regulation of insulin secretion in healthy and
      glucose intolerant subjects.

PMID- 21094636
TI  - The effect of motor imagery on gain modulation of the spinal reflex.
AB  - Motor imagery is well known to have a facilitatory effect on the corticospinal
      tract, but conflicting opinions have arisen concerning its effect on spinal
      reflex excitability. The purpose of this study was to clarify the effects of
      motor imagery on gain modulation of the spinal reflex by focusing on the
      physiological differences between the H-reflex and the stretch reflex. In
      experiment 1, there were three conditions: rest, motor imagery of ankle
      dorsiflexion (MI-DF), and motor imagery of ankle plantarflexion (MI-PF). The
      subjects were instructed to imagine 100% maximum voluntary isometric contraction
      (MI-100) in each direction of movement. To examine the effects of the imagined
      effort level on spinal reflex excitability, the subjects also imagined 50%
      maximum voluntary contraction (MI-50) in experiment 2. The soleus H-reflex and
      the stretch reflex amplitude and background EMG (bEMG) activity were measured.
      There were no significant differences in bEMG activity between the H-reflex and
      stretch reflex measurements. In experiment 1, although the H-reflex amplitude did
      not change significantly among the three conditions, the stretch reflex amplitude
      increased significantly under the MI-DF and MI-PF conditions compared to the rest
      condition. In addition, the stretch reflex amplitude under the MI-100 condition
      was significantly larger than that under the MI-50 condition in experiment 2.
      These results indicate that motor imagery has a selective facilitatory effect on
      stretch reflex pathways. Furthermore, this excitability change may occur in
      untargeted antagonist muscles as well as targeted agonist muscles and may depend
      on the imagined effort level.

PMID- 21094637
TI  - The transmembrane receptor Uncoordinated5 (Unc5) is essential for heart lumen
      formation in Drosophila melanogaster.
AB  - Transport of liquids or gases in biological tubes is fundamental for many
      physiological processes. Our knowledge on how tubular organs are formed during
      organogenesis and tissue remodeling has increased dramatically during the last
      decade. Studies on different animal systems have helped to unravel some of the
      molecular mechanisms underlying tubulogenesis. Tube architecture varies
      dramatically in different organs and different species, ranging from tubes formed
      by several cells constituting the cross section, tubes formed by single cells
      wrapping an internal luminal space or tubes that are formed within a cell. Some
      tubes display branching whereas others remain linear without intersections. The
      modes of shaping, growing and pre-patterning a tube are also different and it is
      still not known whether these diverse architectures and modes of differentiation
      are realized by sharing common signaling pathways or regulatory networks.
      However, several recent investigations provide evidence for the attractive
      hypothesis that the Drosophila cardiogenesis and heart tube formation shares many
      similarities with primary angiogenesis in vertebrates. Additionally, another
      important step to unravel the complex system of lumen formation has been the
      outcome of recent studies that junctional proteins, matrix components as well as
      proteins acting as attractant and repellent cues play a role in the formation of
      the Drosophila heart lumen. In this study we show the requirement for the
      repulsively active Unc5 transmembrane receptor to facilitate tubulogenesis in the
      dorsal vessel of Drosophila. Unc5 is localized in the luminal membrane
      compartment of cardiomyocytes and animals lacking Unc5 fail to form a heart
      lumen. Our findings support the idea that Unc5 is crucial for lumen formation and
      thereby represents a repulsive cue acting during Drosophila heart tube formation.

PMID- 21094639
TI  - Mitogen-activated protein kinase phosphatase-1 (MKP-1) in retinal ischemic
      preconditioning.
AB  - We previously described the phenomenon of retinal ischemic pre-conditioning (IPC)
      and we have shown the role of various signaling proteins in the protective
      pathways, including the mitogen-activated protein kinase p38. In this study we
      examined the role in IPC of mitogen-activated protein kinase phosphatase-1 (MKP
      1), which inactivates p38. Ischemia was produced by elevation of intraocular
      pressure above systolic arterial blood pressure in adult Wistar rats.
      Preconditioning was produced by transient retinal ischemia for 5 min, 24 h prior
      to ischemia. Small interfering RNA (siRNA) to MKP-1 or a control non-silencing
      siRNA, was injected into the vitreous 6 h prior to IPC. Recovery was assessed by
      electroretinography (ERG) and histology. The a-and b-waves, and oscillatory
      potentials (OPs), measured before and 1 week after ischemia, were then normalized
      relative to pre-ischemic baseline, and corrected for diurnal variation in the
      normal non-ischemic eye. The P2, or post-photoreceptor component of the ERG
      (which reflects function of the rod bipolar cells in the inner retina), was
      derived using the Hood-Birch model. MKP-1 was localized in specific retinal cells
      using immunohistochemistry; levels of mitogen-activated protein kinases were
      measured using Western blotting. Injection of siRNA to MKP-1 significantly
      attenuated the protective effect of IPC as reflected by decreased recovery of the
      electroretinogram a and b-waves and the P2 after ischemia. The injection of siRNA
      to MKP-1 reduced the number of cells in the retinal ganglion cell and outer
      nuclear layers after IPC and ischemia. Blockade of MKP-1 by siRNA also increased
      the activation of p38 at 24 h following IPC. MKP-1 siRNA did not alter the levels
      of phosphorylated jun N-terminal kinase (JNK) or extracellular signal-regulated
      kinase (ERK) after IPC. The results suggest the involvement of dual-specificity
      phosphatase MKP-1 in IPC and that MKP-1 is involved in IPC by regulating levels
      of activated MAPK p38.

PMID- 21094640
TI  - Structural mechanism of the antigen recognition by the L1 cell adhesion molecule
      antibody A10-A3.
AB  - The L1CAM antibody A10-A3 efficiently reduces tumor growth in a nude mouse model.
      Here, we describe the crystal structure of the Fab fragment of A10-A3 determined
      at 2.0 angstrom resolution. The A10-A3 antibody H3 loop reveals a characteristic
      arrangement of exposed aromatic residues that may play an important role in
      antigen binding. A structure model of the complex between L1CAM Ig1-4 and A10-A3
      Fab indicates that the Fab binds to three small loops outside Ig1 and a residue
      between Ig1 and Ig2, consistent with an epitope mapping result. The data
      presented here should contribute to the design of high-affinity antibody for
      therapeutic purposes as well as to the understanding of neural cell remodeling
      and cancer progression mechanism mediated by L1CAM.

PMID- 21094638
TI  - Bone morphogenetic proteins regulate enteric gliogenesis by modulating ErbB3
      signaling.
AB  - The neural crest-derived cell population that colonizes the bowel (ENCDC)
      contains proliferating neural/glial progenitors. We tested the hypothesis that
      bone morphogenetic proteins (BMPs 2 and 4), which are known to promote enteric
      neuronal differentiation at the expense of proliferation, function similarly in
      gliogenesis. Enteric gliogenesis was analyzed in mice that overexpress the BMP
      antagonist, noggin, or BMP4 in the primordial ENS. Noggin-induced loss-of
      function decreased, while BMP4-induced gain-of-function increased the glial
      density and glia/neuron ratio. When added to immunoisolated ENCDC, BMPs provoked
      nuclear translocation of phosphorylated SMAD proteins and enhanced both glial
      differentiation and expression of the neuregulin receptor ErbB3. ErbB3
      transcripts were detected in E12 rat gut, before glial markers are expressed;
      moreover, expression of the ErbB3 ligand, glial growth factor 2 (GGF2) escalated
      rapidly after its first detection at E14. ErbB3-immunoreactive cells were located
      in the ENS of fetal and adult mice. GGF2 stimulated gliogenesis and proliferation
      and inhibited glial cell derived neurotrophic factor (GDNF)-promoted
      neurogenesis. Enhanced glial apoptosis occurred following GGF2 withdrawal; BMPs
      intensified this GGF2-dependence and reduced GGF2-stimulated proliferation. These
      observations support the hypotheses that BMPs are required for enteric
      gliogenesis and act by promoting responsiveness of ENCDC to ErbB3 ligands such as
      GGF2.

PMID- 21094641
TI  - Stat3 is essential for neuronal differentiation through direct transcriptional
      regulation of the Sox6 gene.
AB  - The transcription factor Signal Transducer and Activator of Transcription 3
      (Stat3) functions in various cellular processes including neuronal
      differentiation. We show that the SRY-box containing gene 6 (Sox6) gene,
      important for neuronal differentiation, is a direct target gene of Stat3. We
      demonstrate that in response to ligand stimulation, Stat3 binds to the Sox6
      promoter and induces its expression. Furthermore, Stat3 is activated and Sox6 is
      induced during neuronal differentiation of P19 cells in the absence of exogenous
      ligand treatment. Moreover, using an RNA interference approach, we show that
      Stat3 is required for Sox6 expression during neuronal differentiation.

PMID- 21094642
TI  - Structural models of DYNLL1 with interacting partners: African swine fever virus
      protein p54 and postsynaptic scaffolding protein gephyrin.
AB  - DYNLL1, the smallest dynein light chain, interacts with different cargos
      facilitating their cellular transport. Usually the sequence recognized in the
      targets is homologous to the GIQVD or the KXTQT motifs with a glutamine that is
      important for binding. Here we add two new examples of DYNLL1 targets that can be
      classified into these two groups: ASFV p54 and gephyrin. Using NMR we demonstrate
      the direct interaction between DYNLL1 and two peptides derived from their
      interacting sequences. We model the structure of both complexes and show that the
      overall binding mode is preserved as in other complexes despite differences at
      the residue-specific interactions.

PMID- 21094643
TI  - The retroviral proteinase active site and the N-terminus of Ddi1 are required for
      repression of protein secretion.
AB  - The Ddi1 protein of the yeast Saccharomyces cerevisiae is involved in numerous
      interactions with the ubiquitin system, which may be mediated by its N-terminal
      ubiquitin like domain and its C-terminal ubiquitin associated domain. Ddi1 also
      contains a central region with all the features of a retroviral aspartic
      proteinase, which was shown to be important in cell-cycle control. Here we
      demonstrate an additional role for this domain, along with the N-terminal region,
      in protein secretion. These results further substantiate the hypothesis that Ddi1
      functions in vivo as a catalytically-active aspartic proteinase.

PMID- 21094644
TI  - Enhanced acetylation of alpha-tubulin in influenza A virus infected epithelial
      cells.
AB  - Acetylated microtubules (AcMTs), a post-translationally modified form of
      microtubules, promote polarized protein transport. Here we report that influenza
      A virus (IAV) induces the acetylation of microtubules in epithelial cells. By
      employing specific inhibitors and siRNA we demonstrate Rho GTPase-mediated
      downregulation of tubulin deacetylase activity in IAV-infected cells, resulting
      in increased tubulin acetylation. Further, we demonstrate that
      depolymerization/deacetylation or enhanced acetylation of microtubules decreased
      or increased, respectively, the release of virions from infected cells. IAV
      assembly requires the polarized delivery of viral components to apical plasma
      membrane. Our findings suggest the potential involvement of AcMTs in polarized
      trafficking of IAV components.

PMID- 21094645
TI  - Identification, characterization, and molecular cloning of a novel hyaluronidase,
      a member of glycosyl hydrolase family 16, from Penicillium spp.
AB  - Hyaluronidase (HAase) activity was detected in the culture supernatants of
      Penicillium purpurogenum and Penicillium funiculosum. The HAase from Penicillium
      spp. (HAase-P) was a hyaluronate 4-glycanohydrolase, which catalyzed the
      endolytic hydrolysis of the beta-1,4 glycosidic linkage, as do vertebrate HAases.
      The gene encoding HAase-P was cloned and expressed in Escherichia coli. According
      to homology analyses of the deduced amino acid sequences, HAase-P is not
      classified into any of the known HAase groups, but belongs to glycoside hydrolase
      family 16, which includes endo-beta-1,3(4)-glucanase. Regarding the substrate
      specificities, no chondroitinase and glucanase activities were detected. Judging
      from homology analyses and enzymatic properties, HAase-P seems to be a new type
      of HAase.

PMID- 21094646
TI  - Expression, cellular distribution, and heterogeneity of growth hormone in the
      chicken cerebellum during development.
AB  - Although growth hormone (GH) is mainly synthesized and secreted by pituitary
      somatotrophs, it is now well established that the GH gene can be expressed in
      many extrapituitary tissues, including the central nervous system (CNS). Here we
      studied the expression of GH in the chicken cerebellum. Cerebellar GH expression
      was analyzed by in situ hybridization and cDNA sequencing, as well as by
      immunohistochemistry and confocal microscopy. GH heterogeneity was studied by
      Western blotting. We demonstrated that the GH gene was expressed in the chicken
      cerebellum and that its nucleotide sequence is closely homologous to pituitary GH
      cDNA. Within the cerebellum, GH mRNA is mainly expressed in Purkinje cells and in
      cells of the granular layer. GH-immunoreactivity (IR) is also widespread in the
      cerebellum and is similarly most abundant in the Purkinje and granular cells as
      identified by specific neuronal markers and histochemical techniques. The GH
      concentration in the cerebellum is age-related and higher in adult birds than in
      embryos and juveniles. Cerebellar GH-IR, as determined by Western blot under
      reducing conditions, is associated with several size variants (of 15, 23, 26, 29,
      35, 45, 50, 55, 80 kDa), of which the 15 kDa isoform predominates (>30% among all
      developmental stages). GH receptor (GHR) mRNA and protein are also present in the
      cerebellum and are similarly mainly present in Purkinje and granular cells.
      Together, these data suggest that GH and GHR are locally expressed within the
      cerebellum and that this hormone may act as a local autocrine/paracrine factor
      during development of this neural tissue.

PMID- 21094647
TI  - Attenuation of food intake in chicks by an inverse agonist of cannabinoid
      receptor 1 administered by either injection or ingestion in hydrocolloid
      carriers.
AB  - The cannabinoid receptor (CB(1)) was studied primarily in mammals where it was
      found to comprise a link between reward processes and addictive behavior such as
      food consumption. The purpose of this study was twofold: first to characterize
      the effect of the chicken CB(1) receptor inverse agonist AM251 on food intake,
      and second, to establish a stress-free approach for application of AM251 to birds
      using hydrocolloid carriers, which can be mixed with food. A single
      administration of AM251 by intravenous injection (at 0.85 or 5 mg kg(-1)BW) or by
      ingestion of hydrocolloid carriers entrapping AM251 at a concentration of 5 mg
      kg(-1)BW led to a transient attenuation of food intake. The consequent reduced
      cumulative food intake and BW were observed in the treated chicks for at least 7h
      post-administration, with no gender differences. Circulating levels of AM251,
      assessed by LC-MS following 48 h of continuous feeding with hydrocolloid carriers
      containing 50mg AM 251 kg(-1) BW day(-1), were physiologically significant at 186
      +/- 73 pmol ml(-1). It is concluded that unlike some other factors, which act
      differently in birds compared to mammals such as ghrelin, CB(1) inverse agonists
      attenuate food intake in chicks similar to its effect in mammals. In addition,
      the new approach for administration of AM251 to birds in hydrocolloid carriers
      could provide a simple and stress-free tool for prolonged studies of this control
      mechanism in birds.

PMID- 21094649
TI  - Maternal nurturing is dependent on her innate anxiety: the behavioral roles of
      brain oxytocin and vasopressin.
AB  - The maternal brain undergoes remarkable physiological and behavioral changes in
      the peripartum period to meet the demands of the offspring. Here, the brain
      neuropeptides oxytocin and vasopressin, together with prolactin, play important
      roles. These neuropeptides are critically involved in the regulation of maternal
      behavior. Furthermore, reduced anxiety in lactation is another adaptation of the
      maternal brain. Therefore, a link between maternal behavior and maternal anxiety
      has been repeatedly postulated. This is supported by our studies in rats bred for
      high (HAB) and low (LAB) anxiety-related behavior. While female HAB rats become
      less anxious in lactation, their anxiety level is still four times higher
      compared with LAB dams. Interestingly, HAB dams display an intense and protective
      mothering style including increased arched back nursing and pup retrieval whereas
      LAB dams display only low levels of maternal care. The amount of maternal care
      directed towards the pups correlates with the mother's innate anxiety. In
      addition to differences in maternal care, HAB dams are also more protective as
      they show heightened aggression against a virgin intruder compared with the less
      aggressive LAB dams. The level of maternal aggression correlates with both their
      innate anxiety level as well as with the release of oxytocin and vasopressin in
      hypothalamic and limbic brain areas. Importantly, manipulations of the brain
      oxytocin and vasopressin systems alter maternal behavior and - depending on the
      brain region - can also alter the dam's anxiety. Thus, the mother's innate
      anxiety determines her maternal performance and oxytocin and vasopressin are
      involved in both parameters.

PMID- 21094650
TI  - The Structure of Physarum polycephalum hemagglutinin I suggests a minimal
      carbohydrate recognition domain of legume lectin fold.
AB  - Physarum polycephalum hemagglutinin I (HA1) is a 104-residue protein that is
      secreted to extracellular space. The crystal structure of HA1 has a beta-sandwich
      fold found among lectin structures, such as legume lectins and galectins.
      Interestingly, the beta-sandwich of HA1 lacks a jelly roll motif and is
      essentially composed of two simple up-and-down beta-sheets. This up-and-down beta
      sheet motif is well conserved in other legume lectin-like proteins derived from
      animals, plants, bacteria, and viruses. It is more noteworthy that the up-and
      down beta-sheet motif includes many residues that make contact with the target
      carbohydrates. Our NMR data demonstrate that HA1 lacking a jelly roll motif also
      binds to its target glycopeptide. Taken together, these data show that the up-and
      down beta-sheet motif provides a fundamental scaffold for the binding of legume
      lectin-like proteins to the target carbohydrates, and the structure of HA1
      suggests a minimal carbohydrate recognition domain.

PMID- 21094648
TI  - Olfactory preference in the male rat depends on multiple chemosensory inputs
      converging on the preoptic area.
AB  - Both volatile and nonvolatile molecules are involved in chemosensory
      communication in rodents. Volatile odors from physically inaccessible estrous
      females induced increased numbers of c-Fos-positive cells in the preoptic area
      (POA) and in the cortical nucleus of the amygdala (CoA) of male rats. The numbers
      of c-Fos-positive cells in the medial nucleus of the amygdala (MeA) increased in
      response to the nonvolatile odors of bedding soiled with the excreta of estrous
      females. In an alternate choice paradigm, male rats carrying ibotenic acid
      lesions in either the MeA or the CoA--or a combination of both--distinguished the
      odors of estrous females from those of males, although the time spent sniffing
      the stimuli was diminished. Males with POA lesions showed complete loss of this
      capability. Males carrying either of the lesions did not detect differences
      between estrous and anestrous females or between intact and orchidectomized
      males. Lesions in the POA or MeA severely impaired male sexual behavior, whereas
      a CoA lesion had no effects. Thus, c-Fos-positive cells in the CoA might be
      involved in chemosensory transmission relevant to certain social contexts, but
      not in the execution of male sexual behavior. The POA is indispensable for both
      olfactory preferences and sexual behavior. The residual olfactory preference in
      males with MeA or CoA lesions or the combination of both could reflect an
      additional route for chemosensory transmission from the main olfactory bulb to
      the POA.

PMID- 21094652
TI  - Active-site structure of class IV adenylyl cyclase and transphyletic mechanism.
AB  - Adenylyl cyclases (ACs) belonging to three nonhomologous classes (II, III, and
      IV) have been structurally characterized, enabling a comparison of the mechanisms
      of cyclic adenosine 3',5'-monophosphate biosynthesis. We report the crystal
      structures of three active-site complexes for Yersinia pestis class IV AC (AC-IV)
      two with substrate analogs and one with product. Mn(2+) binds to all three
      phosphates, and to Glu12 and Glu136. Electropositive residues Lys14, Arg63,
      Lys76, Lys111, and Arg113 also form hydrogen bonds to phosphates. The
      conformation of the analogs is suitable for in-line nucleophilic attack by the
      ribose O3' on alpha-phosphate (distance ~4 A). In the product complex, a second
      Mn ion is observed to be coordinated to both ribose 2' oxygen and ribose 3'
      oxygen. Observation of both metal sites, together with kinetic measurements,
      provides strong support for a two-cation mechanism. Eleven active-site mutants
      were also made and kinetically characterized. These findings and comparisons with
      class II and class III enzymes enable a detailed transphyletic analysis of the AC
      mechanism. Consistent with its lack of coordination to purine, Y. pestis AC-IV
      cyclizes both ATP and GTP. As in other classes of AC, the ribose is loosely
      bound, and as in class III, no base appears to ionize the O3' nucleophile.
      Different syn/anti conformations suggest that the mechanism involves a
      conformational transition, and further evidence suggests a role for ribosyl
      pseudorotation. With resolutions of 1.6-1.7 A, these are the most detailed active
      site ligand complexes for any class of this ubiquitous signaling enzyme.

PMID- 21094651
TI  - Asymmetric configurations and N-terminal rearrangements in connexin26 gap
      junction channels.
AB  - Gap junction channels are unique in that they possess multiple mechanisms for
      channel closure, several of which involve the N terminus as a key component in
      gating, and possibly assembly. Here, we present electron crystallographic
      structures of a mutant human connexin26 (Cx26M34A) and an N-terminal deletion of
      this mutant (Cx26M34Adel2-7) at 6-A and 10-A resolutions, respectively. The three
      dimensional map of Cx26M34A was improved by data from 60 degrees  tilt images and
      revealed a breakdown of the hexagonal symmetry in a connexin hemichannel,
      particularly in the cytoplasmic domain regions at the ends of the transmembrane
      helices. The Cx26M34A structure contained an asymmetric density in the channel
      vestibule ("plug") that was decreased in the Cx26M34Adel2-7 structure, indicating
      that the N terminus significantly contributes to form this plug feature.
      Functional analysis of the Cx26M34A channels revealed that these channels are
      predominantly closed, with the residual electrical conductance showing normal
      voltage gating. N-terminal deletion mutants with and without the M34A mutation
      showed no electrical activity in paired Xenopus oocytes and significantly
      decreased dye permeability in HeLa cells. Comparing this closed structure with
      the recently published X-ray structure of wild-type Cx26, which is proposed to be
      in an open state, revealed a radial outward shift in the transmembrane helices in
      the closed state, presumably to accommodate the N-terminal plug occluding the
      pore. Because both Cx26del2-7 and Cx26M34Adel2-7 channels are closed, the N
      terminus appears to have a prominent role in stabilizing the open configuration.

PMID- 21094653
TI  - Visuomotor integration deficits precede clinical onset in Huntington's disease.
AB  - OBJECTIVES: Visuomotor integration deficits have been documented in Huntington
      disease (HD), with disproportionately more impairment when direct visual feedback
      is unavailable. Visuomotor integration under direct and indirect visual feedback
      conditions has not been investigated in the stage before clinical onset
      ('premanifest'). However, given evidence of posterior cortical atrophy in
      premanifest HD, we predicted visuomotor integration would be adversely affected,
      with greater impairment under conditions of indirect visual feedback. METHODS:
      239 subjects with the HD CAG expansion, ranging from more than a decade before
      predicted clinical onset until early stage disease, and 122 controls, completed a
      circle-tracing task, which included both direct and indirect visual feedback
      conditions. Measures included accuracy, speed, and speed of error detection and
      correction. Using brain images acquired with 3T magnetic resonance imaging (MRI),
      we generated grey and white matter volumes with voxel-based morphometry, and
      analyzed correlations with circle-tracing performance. RESULTS: Compared with
      controls, early HD was associated with lower accuracy and slower performance in
      both circle-tracing conditions. Premanifest HD was associated with lower accuracy
      in both conditions and fewer rotations in the direct condition. Comparing
      performance in the indirect condition with the direct condition, HD gene
      expansion-carriers exhibited a disproportionate increase in errors relative to
      controls. Premanifest and early HD groups required longer to detect and correct
      errors, especially in the indirect condition. Slower performance in the indirect
      condition was associated with lower grey matter volumes in the left somatosensory
      cortex in VBM analyses. CONCLUSIONS: Visuomotor integration deficits are evident
      many years before the clinical onset of HD, with deficits in speed, accuracy, and
      speed of error detection and correction. The visuomotor transformation demands of
      the indirect condition result in a disproportionate decrease in accuracy in the
      HD groups. Slower performance under indirect visual feedback was associated with
      atrophy of the left-hemisphere somatosensory cortex, which may reflect the
      proprioceptive demands of the task.

PMID- 21094654
TI  - A long-lasting improvement of tactile extinction after galvanic vestibular
      stimulation: two Sham-stimulation controlled case studies.
AB  - Sensory extinction is frequent and often persistent after brain damage. Previous
      studies have shown the transient influence of sensory stimulation on tactile
      extinction. In the present two case studies we investigated whether subliminal
      galvanic vestibular stimulation (GVS) modulates tactile extinction. GVS induces
      polarity-specific changes in cerebral excitability in the vestibular cortices and
      adjacent cortical areas in the temporo-parietal cortex via polarization of the
      vestibular nerves. Two patients (DL, CJ) with left-sided tactile extinction due
      to chronic (5 vs. 6 (1/2) years lesion age) right-hemisphere lesions (right
      fronto-parietal in DL, right frontal and discrete parietal in CJ) were examined.
      Both showed normal tactile sensitivity to light touch and yielded 90-100% correct
      identifications in unilateral tactile stimulations for both hands. In Baseline
      investigations without GVS and Sham-GVS both showed stable left-sided tactile
      extinction rates of 40-55% (DL) and 49-72% (CJ). In contrast, one session of
      right-cathodal GVS (intensity: 0.6 mA, duration: 20 min) permanently improved
      tactile identification of identical stimuli, while a second session with left
      cathodal GVS significantly reduced left-sided extinction rates for different
      stimuli in DL. Patient CJ's left-sided tactile extinction was significantly
      improved by left-cathodal GVS (0.5 mA, 20 min) for different stimuli, while right
      cathodal GVS induced a significant reduction for identical materials. In
      contrast, Sham-stimulation was ineffective. Improvements remained stable for at
      least 1 year (DL) resp. 3 weeks (CJ). Control experiments ruled out improvements
      in tactile extinction merely by retesting. In conclusion, chronic tactile
      extinction may be permanently improved by GVS in a polarity-specific way.

PMID- 21094655
TI  - Properties of Weir and Cockerham's Fst estimators and associated bootstrap
      confidence intervals.
AB  - Weir and Cockerham introduced single locus and multiloci F(st) estimators for the
      parameter theta. These estimators are commonly used, but little beyond their bias
      and variance is known. In this work, we develop formulas that allow us to
      describe how the underlying value of theta and the genetic diversity of sampled
      loci affect the distributions of these estimators. We show that in certain
      settings, these estimators are close to normal, while in others they are far from
      normal. We use these results to analyze confidence interval construction for
      theta, showing that the percentile-t bootstrap works well while the BCa bootstrap
      works poorly. Our results are derived using a novel coalescent based method.

PMID- 21094656
TI  - A physiologically based pharmacokinetic model for atrazine and its main
      metabolites in the adult male C57BL/6 mouse.
AB  - Atrazine (ATR) is a chlorotriazine herbicide that is widely used and relatively
      persistent in the environment. In laboratory rodents, excessive exposure to ATR
      is detrimental to the reproductive, immune, and nervous systems. To better
      understand the toxicokinetics of ATR and to fill the need for a mouse model, a
      physiologically based pharmacokinetic (PBPK) model for ATR and its main
      chlorotriazine metabolites (Cl-TRIs) desethyl atrazine (DE), desisopropyl
      atrazine (DIP), and didealkyl atrazine (DACT) was developed for the adult male
      C57BL/6 mouse. Taking advantage of all relevant and recently made available mouse
      specific data, a flow-limited PBPK model was constructed. The ATR and DACT sub
      models included blood, brain, liver, kidney, richly and slowly perfused tissue
      compartments, as well as plasma protein binding and red blood cell binding,
      whereas the DE and DIP sub-models were constructed as simple five-compartment
      models. The model adequately simulated plasma levels of ATR and Cl-TRIs and
      urinary dosimetry of Cl-TRIs at four single oral dose levels (250, 125, 25, and
      5mg/kg). Additionally, the model adequately described the dose dependency of
      brain and liver ATR and DACT concentrations. Cumulative urinary DACT amounts were
      accurately predicted across a wide dose range, suggesting the model's potential
      use for extrapolation to human exposures by performing reverse dosimetry. The
      model was validated using previously reported data for plasma ATR and DACT in
      mice and rats. Overall, besides being the first mouse PBPK model for ATR and its
      Cl-TRIs, this model, by analogy, provides insights into tissue dosimetry for
      rats. The model could be used in tissue dosimetry prediction and as an aid in the
      exposure assessment to this widely used herbicide.

PMID- 21094657
TI  - Oxytocin response in a trust game and habituation of arousal.
AB  - Oxytocin may be implicated in various sophisticated human processes, including
      attachment, trust, social perception, memory, and fear regulation. In this study,
      we explored the relationship between plasma oxytocin level measured after a task
      requiring intimate trust (secret sharing) and habituation of autonomic arousal
      (skin conductance response) in sixty healthy volunteers. Results revealed that
      oxytocin was elevated in the trust-related condition relative to a neutral
      baseline. In a cognitive stress condition (mental arithmetic task), there was no
      significant oxytocin elevation relative to the neutral condition. After
      controlling for age, gender, education, state anxiety and depression, we found a
      significant positive relationship between trust-related oxytocin level and
      habituation of autonomic arousal. This relationship was absent in the case of
      neutral (trust-unrelated) oxytocin level. These results suggest that the
      habituation of autonomic arousal is closely related to oxytocin released during
      trust-related social interactions.

PMID- 21094658
TI  - Water hemlock poisoning in cattle: Ingestion of immature Cicuta maculata seed as
      the probable cause.
AB  - It is well understood that water hemlock tubers are highly toxic to animals and
      to humans. However, this is the first time that immature seed from (Cicuta
      maculata) has been implicated in livestock poisoning. Nine mature Hereford cows
      from a herd of 81 died in northwestern Utah after ingesting immature seed heads
      of water hemlock (Cicuta maculata) in late summer. No obvious signs of poisoning
      were reported as all nine were found dead near the banks of the stream where
      water hemlock was found. Upon discovery of the dead cows, the remaining 72 cows
      were immediately removed from the pasture and no further losses occurred. Field
      necropsy of 3 of the dead cows and follow-up serology and histopathological
      examination of selected tissues did not identify any bacterial or viral causes.
      History of ingestion of large quantities of water hemlock seed, the acute nature
      of the deaths, chemical comparison of seed with toxic tubers and follow-up mouse
      bioassay testing supported the diagnosis of water hemlock poisoning. Seed heads
      collected from the neighboring pasture upstream and across the fence from the
      poisoned cattle and tubers collected from grazed plants were chemically analyzed
      and found to contain cicutoxin, and high levels of two cicutol-like derivatives
      (cicutol-#1 and #2) as well as other unidentified polyacetylene compounds. Seeds
      and tubers from suspected plants were semi-quantified and compared to archive
      samples of highly toxic tubers used in previous experiments. The immature hemlock
      seed contained less cicutoxin (0.01 times), but 9.5 and 22.5 times more cicutol
      #1 and cicutol-#2 respectively, compared to the archive sample. Tubers from the
      grazed plants contained 4.6 times more cicutoxin and 9.8 and 18.8 times more
      cicutol-#1 and cicutol-#2 respectively, compared to the archive sample. Mouse
      bioassays with water extracts of immature seed and tubers from grazed plants
      demonstrated both were highly toxic and of greater toxicity when compared to
      archived sample.

PMID- 21094659
TI  - RAS oncogene-mediated deregulation of the transcriptome: from molecular signature
      to function.
AB  - Transcriptome analysis of cancer cells has developed into a standard procedure to
      elucidate multiple features of the malignant process and to link gene expression
      to clinical properties. Gene expression profiling based on microarrays provides
      essentially correlative information and needs to be transferred to the functional
      level in order to understand the activity and contribution of individual genes or
      sets of genes as elements of the gene signature. To date, there exist significant
      gaps in the functional understanding of gene expression profiles. Moreover, the
      processes that drive the profound transcriptional alterations that characterize
      cancer cells remain mainly elusive. We have used pathway-restricted gene
      expression profiles derived from RAS oncogene-transformed cells and from RAS
      expressing cancer cells to identify regulators downstream of the MAPK pathway.We
      describe the role of epigenetic regulation exemplified by the control of several
      immune genes in generic cell lines and colorectal cancer cells, particularly the
      functional interaction between signaling and DNA methylation. Moreover, we assess
      the role of the architectural transcription factor high mobility AT-hook 2
      (HMGA2) as a regulator of the RAS-responsive transcriptome in ovarian epithelial
      cells. Finally, we describe an integrated approach combining pathway interference
      in colorectal cancer cells, gene expression profiling and computational analysis
      of regulatory elements of deregulated target genes. This strategy resulted in the
      identification of Y-box binding protein 1 (YBX1) as a regulator of MAPK-dependent
      proliferation and gene expression. The implications for a therapeutic application
      of HMGA2 gene silencing and the role of YBX1 as a prognostic factor are
      discussed.

PMID- 21094660
TI  - The song remains the same: coactivators and sex differences in the songbird
      brain.
AB  - The majority of songbird species have sexually dimorphic neuronal circuits for
      song learning and production and these differences are paralleled by sex
      differences in behavior, with only males singing or singing at a higher rate than
      females. Therefore songbirds serve as an excellent model for studying the
      mechanisms that influence the sexually dimorphic development of the brain and
      behavior. Past research focused on the actions of steroid hormones or their
      receptors in the development of these sex differences. This review examines the
      distribution and action of steroid receptor coactivators in the songbird brain;
      more specifically the actions of RPL7, SRC-1, and CBP on the song control system.
      Coactivators enhance the transcriptional activity of the nuclear steroid
      receptors with which they associate, and therefore may play a role in modulating
      the development of sex differences in the brain and behavior. The actions of
      these proteins may help elucidate the hormonal mechanisms that underlie song
      nuclei development and steroid activated singing behavior in adulthood.

PMID- 21094661
TI  - Dying for a smoke: how much does differential mortality of smokers affect
      estimated life-course smoking prevalence?
AB  - OBJECTIVE: An extensive literature uses reconstructed historical smoking rates by
      birth-cohort to inform anti-smoking policies. This paper examines whether and how
      these rates change when one adjusts for differential mortality of smokers and non
      smokers. METHODS: Using retrospectively reported data from the US (Panel Study of
      Income Dynamics, 1986, 1999, 2001, 2003, 2005), the UK (British Household Panel
      Survey, 1999, 2002), and Russia (Russian Longitudinal Monitoring Study, 2000), we
      generate life-course smoking prevalence rates by age-cohort. With cause-specific
      death rates from secondary sources and an improved method, we correct for
      differential mortality, and we test whether adjusted and unadjusted rates
      statistically differ. With US data (National Health Interview Survey, 1967-2004),
      we also compare contemporaneously measured smoking prevalence rates with the
      equivalent rates from retrospective data. RESULTS: We find that differential
      mortality matters only for men. For Russian men over age 70 and US and UK men
      over age 80 unadjusted smoking prevalence understates the true prevalence. The
      results using retrospective and contemporaneous data are similar. CONCLUSIONS:
      Differential mortality bias affects our understanding of smoking habits of old
      cohorts and, therefore, of inter-generational patterns of smoking. Unless one
      focuses on the young, policy recommendations based on unadjusted smoking rates
      may be misleading.

PMID- 21094662
TI  - Clinical usefulness of combination chemotherapy for pulmonary Mycobacterium avium
      complex disease.
AB  - BACKGROUND: This study compared the clinical usefulness of combination
      chemotherapy including various doses of clarithromycin (CAM) for pulmonary
      Mycobacterium avium complex (MAC) disease. METHODS: The subjects were divided
      into three groups receiving combination chemotherapy at various dose levels of
      CAM. The analysis of microbiological effects was based on the sputum conversion
      rate and sputum relapsing rate and that of clinical effects was performed by
      clinical symptoms and radiological findings for patients with pulmonary MAC
      disease. RESULTS: There were no significant differences among the three groups
      with regard to patient characteristics. The sputum conversion rate significantly
      increased with the dose of CAM (CAM 400mg: 43%, CAM 600mg: 69%, CAM 800mg: 88%).
      The sputum relapsing rate did not significantly differ among the three groups
      (CAM 400mg: 47%, CAM 600mg: 35%, CAM 800mg: 33%). Along with the sputum
      conversion rate, the rate of clinical improvement was significantly increased
      with the dose of CAM (CAM 400mg: 27%, CAM 600mg: 40%, CAM 800mg: 54%). Adverse
      reactions, such as gastrointestinal symptoms, were most frequently recognized in
      the group receiving CAM 800mg (38%) compared to those in the other two groups
      (CAM 400mg: 23% and CAM 600mg: 25%). CONCLUSIONS: Although both the sputum
      conversion rate and clinical improvement significantly increased with the dose of
      CAM, the rate of adverse reactions, such as gastrointestinal symptoms, also
      increased. It is important to continue close monitoring of patients with
      pulmonary MAC disease treated with a regimen that includes CAM 800mg.

PMID- 21094663
TI  - Dynamic causal modeling with genetic algorithms.
AB  - In the last years, dynamic causal modeling has gained increased popularity in the
      neuroimaging community as an approach for the estimation of effective
      connectivity from functional magnetic resonance imaging (fMRI) data. The
      algorithm calls for an a priori defined model, whose parameter estimates are
      subsequently computed upon the given data. As the number of possible models
      increases exponentially with additional areas, it rapidly becomes inefficient to
      compute parameter estimates for all models in order to reveal the family of
      models with the highest posterior probability. In the present study, we developed
      a genetic algorithm for dynamic causal models and investigated whether this
      evolutionary approach can accelerate the model search. In this context, the
      configuration of the intrinsic, extrinsic and bilinear connection matrices
      represents the genetic code and Bayesian model selection serves as a fitness
      function. Using crossover and mutation, populations of models are created and
      compared with each other. The most probable ones survive the current generation
      and serve as a source for the next generation of models. Tests with artificially
      created data sets show that the genetic algorithm approximates the most plausible
      models faster than a random-driven brute-force search. The fitness landscape
      revealed by the genetic algorithm indicates that dynamic causal modeling has
      excellent properties for evolution-driven optimization techniques.

PMID- 21094664
TI  - The benzodiazepine diazepam demonstrates the usefulness of Syrian hamsters as a
      model for anxiety testing: evaluation of other classes of anxiolytics in
      comparison to diazepam.
AB  - Clinical evidence in humans suggests that there is some linkage between
      dysfunction in the timing of circadian rhythms and certain types of depression.
      In animal models, Syrian hamsters have been used extensively to study the
      pharmacology of circadian rhythms, while rats and mice are used to screen
      putative anxiolytics/antidepressant compounds. It would be beneficial to be able
      to test anxiolytic/antidepressant compounds in hamsters in conjunction with
      circadian rhythm studies. Therefore, in this study, Syrian hamsters were used in
      three experimental paradigms to evaluate anxiety: the elevated plus maze, the t
      tube, and the open field Thatcher-Britton conflict test. Diazepam, tested with
      2mg/kg and 5mg/kg intraperitoneal injections, was found to induce anxiolytic
      activity in each of the three tests. Hamsters were more likely to spend time in
      the open arms in the plus maze, displayed more exploratory behavior in the t
      tube, and were quicker to enter a brightly lit exposed field in the Thatcher
      Britton conflict test following injections of diazepam. Diazepam (2mg/kg) was
      also tested at three times during the 24-h day in the elevated plus maze: at the
      beginning and end of the lights-on period (Zeitgeber times 23 and 11,
      respectively) and once in the dark just before the room lights came on (Zeitgeber
      time 20). Diazepam induced anxiolytic activity only at Zeitgeber 23. Therefore,
      the following known and putative anxiolytic compounds were also evaluated in each
      of the three tests at Zeitgeber 23: citalopram, the neurokinin(1) receptor
      antagonists GR205171 and vestipitant, the corticotropin releasing factor(1)
      receptor antagonist CP154526, the cannabinoid receptor(1) agonist CP55940, the
      serotonin(6) receptor antagonist SB399885, and the metabotropic glutamate
      receptor(5) antagonists fenobam and MTEP. Vestipitant displayed some anxiolytic
      activity in the elevated plus maze, but this effect was not confirmed with
      GR205171. None of the other compounds displayed any anxiolytic activity in the
      tests. Nevertheless, the present results with diazepam - together with a few
      reports from other laboratories, indicate that the elevated plus maze may be a
      suitable procedure for evaluating the actions of anxiolytic compounds in Syrian
      hamsters. In view of current interest in novel classes of psychotropic agent
      interacting with diverse GABA(A) receptor recognition sites, further
      characterization appears justified.

PMID- 21094665
TI  - VAMP3 is associated with endothelial weibel-palade bodies and participates in
      their Ca(2+)-dependent exocytosis.
AB  - Weibel-Palade bodies (WPBs) are secretory organelles of endothelial cells that
      store the thrombogenic glycoprotein von Willebrand factor (vWF). Endothelial
      activation, e.g. by histamine and thrombin, triggers the Ca(2+)-dependent
      exocytosis of WPB that releases vWF into the vasculature and thereby initiates
      platelet capture and thrombus formation. Towards understanding the molecular
      mechanisms underlying this regulated WPB exocytosis, we here identify components
      of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) machinery associated with WPB. We show that vesicle-associated membrane
      protein (VAMP) 3 and VAMP8 are present on WPB and that VAMP3, but not VAMP8 forms
      a stable complex with syntaxin 4 and SNAP23, two plasma membrane-associated
      SNAREs in endothelial cells. By introducing mutant SNARE proteins into
      permeabilized endothelial cells we also show that soluble VAMP3 but not VAMP8
      mutants comprising the cytoplasmic domain interfere with efficient vWF secretion.
      This indicates that endothelial cells specifically select VAMP 3 over VAMP8 to
      cooperate with syntaxin 4 and SNAP23 in the Ca(2+)-triggered fusion of WPB with
      the plasma membrane. This article is part of a Special Issue entitled: 11th
      European Symposium on Calcium.

PMID- 21094667
TI  - Eating at the university canteen. Associations with socioeconomic status and
      healthier self-reported eating habits in France.
AB  - French university canteens offer structured meals at a fixed moderate price. We
      examined whether eating regularly at university canteens was associated with
      socioeconomic status (SES) or dietary practices. The study data came from a cross
      sectional study of a random sample of 1723 students aged 18-24 years, in their
      first year of university in 2005-2006, enrolled in the universities of
      southeastern France (response rate=71%). Self-reported dietary practices were
      collected with a behavioral questionnaire. Adjusted logistic regressions showed
      that eating regularly at university canteens was less frequent among students
      with less than ? 300 monthly resources and not living with their families
      (OR=0.68 [95%CI: 0.49-0.94]). It was also positively associated, regardless of
      SES, with the consumption of at least five servings of fruit/vegetables daily
      (OR=1.42 [1.05-1.92]) and one serving of meat/fish daily (OR=1.41 [1.13-1.76])
      but not with either restricting fatty food (OR=1.04 [0.81-1.33]) or never/rarely
      adding salt to food (OR=1.06 [0.85-1.32]). Eating regularly at university
      canteens was less frequent among less well-off students and was positively
      associated with some healthier self-reported dietary habits. Further research is
      needed to confirm these results in the overall student population in France and
      to understand the determinants of university canteen utilization.

PMID- 21094668
TI  - A review of mammalian carcinogenicity study design and potential effects of
      alternate test procedures on the safety evaluation of food ingredients.
AB  - Extensive experience in conducting long term cancer bioassays has been gained
      over the past 50 years of animal testing on drugs, pesticides, industrial
      chemicals, food additives and consumer products. Testing protocols for the
      conduct of carcinogenicity studies in rodents have been developed in Guidelines
      promulgated by regulatory agencies, including the US EPA (Environmental
      Protection Agency), the US FDA (Food and Drug Administration), the OECD
      (Organization for Economic Co-operation and Development) for the EU member states
      and the MAFF (Ministries of Agriculture, Forestries and Fisheries) and MHW
      (Ministry of Health and Welfare) in Japan. The basis of critical elements of the
      study design that lead to an accepted identification of the carcinogenic hazard
      of substances in food and beverages is the focus of this review. The approaches
      used by entities well-known for carcinogenicity testing and/or guideline
      development are discussed. Particular focus is placed on comparison of testing
      programs used by the US National Toxicology Program (NTP) and advocated in OECD
      guidelines to the testing programs of the European Ramazzini Foundation (ERF), an
      organization with numerous published carcinogenicity studies. This focus allows
      for a good comparison of differences in approaches to carcinogenicity testing and
      allows for a critical consideration of elements important to appropriate
      carcinogenicity study designs and practices. OECD protocols serve as good
      standard models for carcinogenicity testing protocol design. Additionally, the
      detailed design of any protocol should include attention to the rationale for
      inclusion of particular elements, including the impact of those elements on study
      interpretations. Appropriate interpretation of study results is dependent on
      rigorous evaluation of the study design and conduct, including differences from
      standard practices. Important considerations are differences in the strain of
      animal used, diet and housing practices, rigorousness of test procedures, dose
      selection, histopathology procedures, application of historical control data,
      statistical evaluations and whether statistical extrapolations are supported by,
      or are beyond the limits of, the data generated. Without due consideration, there
      can be result conflicting data interpretations and uncertainty about the
      relevance of a study's results to human risk. This paper discusses the critical
      elements of rodent (rat) carcinogenicity studies, particularly with respect to
      the study of food ingredients. It also highlights study practices and procedures
      that can detract from the appropriate evaluation of human relevance of results,
      indicating the importance of adherence to international consensus protocols, such
      as those detailed by OECD.

PMID- 21094666
TI  - Redox regulation of the mitochondrial K(ATP) channel in cardioprotection.
AB  - The mitochondrial ATP-sensitive potassium channel (mK(ATP)) is important in the
      protective mechanism of ischemic preconditioning (IPC). The channel is reportedly
      sensitive to reactive oxygen and nitrogen species, and the aim of this study was
      to compare such species in parallel, to build a more comprehensive picture of
      mK(ATP) regulation. mK(ATP) activity was measured by both osmotic swelling and
      Tl(+) flux assays, in isolated rat heart mitochondria. An isolated adult rat
      cardiomyocyte model of ischemia-reperfusion (IR) injury was also used to
      determine the role of mK(ATP) in cardioprotection by nitroxyl. Key findings were
      as follows: (i) mK(ATP) was activated by O(2)(-) and H(2)O(2) but not other
      peroxides. (ii) mK(ATP) was inhibited by NADPH. (iii) mK(ATP) was activated by S
      nitrosothiols, nitroxyl, and nitrolinoleate. The latter two species also
      inhibited mitochondrial complex II. (iv) Nitroxyl protected cardiomyocytes
      against IR injury in an mK(ATP)-dependent manner. Overall, these results suggest
      that the mK(ATP) channel is activated by specific reactive oxygen and nitrogen
      species, and inhibited by NADPH. The redox modulation of mK(ATP) may be an
      underlying mechanism for its regulation in the context of IPC. This article is
      part of a Special Issue entitled: Mitochondria and Cardioprotection.

PMID- 21094669
TI  - Olanzapine enhances anxiety response to an SSRI in a woman with bipolar disorder.

PMID- 21094670
TI  - Impact of blue vs red light on retinal response of patients with seasonal
      affective disorder and healthy controls.
AB  - OBJECTIVES: Seasonal affective disorder (SAD) is characterized by a mood lowering
      in autumn and/or winter followed by spontaneous remission in spring or summer.
      Bright light (BL) is recognized as the treatment of choice for individuals
      affected with this disease. It was speculated that BL acts on photosensitive
      retinal ganglion cells, particularly sensitive to blue light, which led to the
      emergence of apparatus enriched with blue light. However, blue light is more at
      risk to cause retinal damage. In addition, we reported using electroretinography
      (ERG) that a 60 min exposure of BL could reduce rod sensitivity. The goal of the
      present study was to verify if this decreased in sensitivity could be a
      consequence of the blue light portion present in the white light therapy lamps.
      We also wanted to assess the effect of monochromatic blue light vs red light in
      both healthy controls and patients with SAD. METHOD: 10 healthy subjects and 10
      patients with SAD were exposed in a random order for 60 min to two different
      light colors (red or blue) separated by an interval of at least 1 day. Cone and
      rod ERG luminance-response function was assessed after light exposure. RESULTS: A
      two-way ANOVA indicates that blue light decreases the maximal ERG response (Vmax)
      in both groups in photopic (p<0.05) and scotopic conditions (p<0.01). CONCLUSION:
      The main finding of this experiment is that blue light reduces photoreceptor
      responses after only a single administration. This brings important concerns with
      regard to blue-enriched light therapy lamps used to treat SAD symptoms and other
      disorders.

PMID- 21094671
TI  - Inhibitory action of methadone and its metabolites on erg-mediated K+ current in
      GH3 pituitary tumor cells.
AB  - Methadone (Mtd) is a widely used opioid drug associated with the side effect of
      hyperprolactinemia. The mechanism of how Mtd induces prolactin secretion remains
      unclear. The effects of Mtd and its two main metabolites (EDDP: (+/-)-2-ethyl-1,5
      dimethyl-3,3-diphenylpyrrolinium percholarate and EMDP: 2-ethyl-5-methyl-3,3
      dipnehyl-1-pyrroline) on ion currents were investigated in GH3 pituitary tumor
      cells. Hyperpolarization-elicited K+ currents in GH3 cells bathed in a high-K(+),
      Ca(2+)-free solution were studied to evaluate the effects of Mtd and other
      related compounds on the ether-a-go-go-related-gene (erg) K(+) current
      (I(K(erg))). Mtd suppressed the amplitude of I(K(erg)) in a concentration
      dependent manner with an IC(50) value of 10.4 MUM. With the aid of a minimal
      binding scheme, the inhibitory action of Mtd on I(K(erg)) was estimated with a
      dissociation constant of 8.2 MUM. Mtd tended to increase the rate of I(K(erg))
      deactivation in a voltage-dependent fashion. EDDP (10 MUM) had no effect on
      I(K(erg)), while EMDP (10MUM) slightly suppressed it. In GH3 cells incubated with
      naloxone (30 MUM), the Mtd-induced inhibition of I(K(erg)) remained unaltered.
      Under cell-attached voltage-clamp recordings, Mtd increased the frequency of
      spontaneous action currents with no change in current amplitude. Similarly, Mtd
      can suppress I(K(erg)) in differentiated NG108-15 cells; dynorphin A(1-13) did
      not reverse Mtd-induced inhibition of I(K(erg)). This study shows that Mtd has a
      depressant effect on I(K(erg)), and suggests its ability to affect membrane
      excitability and prolactin secretion. The cyclization of Mtd, in which EDDP and
      EMDP are formed, tends to be critical in removal of the Mtd binding to erg K+
      channel.

PMID- 21094672
TI  - Negative regulation of RPE cell attachment by carbohydrate-dependent cell surface
      binding of galectin-3 and inhibition of the ERK-MAPK pathway.
AB  - Adhesion and spreading of retinal pigment epithelial (RPE) cells on fibronectin
      rich extracellular matrices is a crucial event in the pathogenesis of
      proliferative vitreoretinopathy (PVR). In the present study we explored the
      capacity of galectin-3, a beta-galactoside-binding endogenous lectin, to inhibit
      early PVR-associated cellular events from a therapeutic perspective. We assessed
      the relative expression levels of galectin-3 in native RPE and dedifferentiated,
      cultured RPE. Galectin-3 was constitutively expressed under in vivo and in vitro
      conditions and was abundant in cultured cells. Treatment of human RPE cells with
      soluble galectin-3 disclosed no toxicity within control limits up to 250 MUg/ml.
      When added to the medium, galectin-3 dose-dependently inhibited attachment and
      spreading of the cells on fibronectin by more than 75%. When coated on the
      plastic surface, galectin-3 alone impaired attachment and spreading of RPE cells,
      and reduced attachment but not spreading on fibronectin. Galectin-3 bound to the
      cell surface, and, as determined by the use of the competing sugar beta-lactose,
      galectin-3-mediated effects were dependent on carbohydrate binding. To ascertain
      the role of the ability of galectin-3 to form pentamers, we proteolytically
      removed the N-terminal, cross-linking section. The remaining C-terminal
      carbohydrate-binding domain alone failed to bind to cells and was functionally
      inactive. These results emphasize the relevance of both properties, i.e., glycan
      binding and cross-linking of glycan moieties, for the inhibitory activity of
      galectin-3. Incubation of mobilized RPE cells with galectin-3 significantly
      disturbed microfilament assembly and, in correlation with decreased attachment,
      inhibited ERK phosphorylation. Therefore, galectin-3, acting as a cross-linking
      lectin on the cell surface, negatively regulates attachment and spreading of RPE
      cells in vitro. This effect, at least in part, is attributed to an inhibition of
      the ERK-MAPK pathway, which prevents cytoskeletal rearrangements needed for RPE
      cell attachment and spreading. Further investigation at this pathway may disclose
      a promising nouveau perspective for treatment and prophylaxis of early PVR.

PMID- 21094673
TI  - Counter-regulation of cholinesterases: differential activation of PKC and ERK
      signaling in retinal cells through BChE knockdown.
AB  - The ubiquitous cholinesterase (ChE) enzymes, functioning in the termination of
      acetylcholine mediated neural transmission, are also reported to have additional
      functions. Through application of siRNAs against butyrylcholinesterase (BChE) in
      R28 cells, a retinal cell line with pluripotent properties, a counter-regulation
      between ChEs was revealed. BChE knock down resulted in an up-regulation of not
      only acetylcholinesterase (AChE), but also altered the signaling status of PKC
      and ERK. Knockdown of BChE modified ERK signaling most notably through ERK1/2
      proteins, together with the transcription activator P90RSK1 and c-fos.
      Stimulation of the R28 cell line by forskolin revealed that ChEs are involved in
      an intricate cross talk between different signaling pathways. Forskolin
      stimulated R28 cells displayed a robust cholinergic response, as detected by both
      electrophysiology and ChE expression, and changed the activation status of
      PKC/ERK signaling pathways. The findings in R28 cells show that ChE expressions
      are inversely co-regulated and act through the transcription factors c-fos and
      P90RSK1. Since R28 cells have the capacity to differentiate into different cell
      types through stimulation of signaling pathways, ChEs are likely to be associated
      with cell fate determination, rather than just terminating cholinergic responses.

PMID- 21094674
TI  - Interaction of the N-terminus of ecdysone receptor isoforms with the ligand
      binding domain.
AB  - Ecdysone receptor (EcR) isoforms exert different biological functions, although
      they vary only in their N-terminal domain. Despite identical C-termini, which
      mediate hormone-induced activity, the influence of ligand is isoform specific,
      which indicates an N/C-interaction. The position of helix 12 with and without
      hormone varies among isoforms and modifies N/C-interaction determined by
      fluorescence resonance-energy transfer (FRET), which depends on the salt bridge
      between helices 4 and 12 of the ligand-binding domain (LBD). Disruption of the
      salt bridge by mutation of K497 (helix 4) had no effect on basal N/C-interaction,
      but prevented the hormone-induced increase, which was partially restored by a
      salt bridge with reversed polarity. The heterodimerization partner Ultraspiracle
      (Usp) can compensate for the disruption of the salt bridge. Without ligand the AB
      domains of EcR-A and EcR-B1, but not EcR-B2, interact with the LBD via K497 and
      repress transcriptional activity. This intramolecular cross talk between N- and C
      terminus along with the position of helix 12 stabilized by K497 regulates
      transcriptional activity of EcR isoforms.

PMID- 21094675
TI  - Behavioral insights from mouse models of forebrain--and amygdala-specific
      glucocorticoid receptor genetic disruption.
AB  - Genetic modulation of glucocorticoid receptor (GR) function in the brain using
      transgenic and gene knockout mice has yielded important insights into many
      aspects of GR effects on behavior and neuroendocrine responses, but significant
      limitations regarding interpretation of region-specific and temporal requirements
      remain. Here, we summarize the behavioral phenotype associated with two knockout
      mouse models to define the role of GRs specifically within the forebrain and
      amygdala. We report that forebrain-specific GR knockout mice exhibit impaired
      negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis and
      increased despair- and anxiety-like behaviors. In addition, mice with a
      disruption of GR specifically within the central nucleus of the amygdala (CeA)
      are deficient in conditioned fear behavior. Overall, these models serve as
      beneficial tools to better understand the biology of GR signaling in the normal
      stress response and in mood disorders.

PMID- 21094676
TI  - Localization of Sonic hedgehog secreting and receiving cells in the developing
      and adult rat adrenal cortex.
AB  - Sonic hedgehog signaling was recently demonstrated to play an important role in
      murine adrenal cortex development. The organization of the rat adrenal differs
      from that of the mouse, with the zona glomerulosa and zona fasciculata separated
      by an undifferentiated zone in the rat, but not in the mouse. In the present
      study we aimed to determine the mRNA expression patterns of Sonic hedgehog and
      the hedgehog signaling pathway components Patched-1 and Gli1 in the developing
      and adult rat adrenal. Sonic hedgehog expression was detected at the periphery of
      the cortex in cells lacking CYP11B1 and CYP11B2 expression, while signal
      receiving cells were localized in the overlying capsule mesenchyme. Using
      combined in situ hybridization and immunohistochemistry we found that the cells
      expressing Sonic hedgehog lie between the CYP11B2 and CYP11B1 layers, and thus
      Sonic hedgehog expression defines one cell population of the undifferentiated
      zone.

PMID- 21094677
TI  - Adrenocortical stem and progenitor cells: unifying model of two proposed origins.
AB  - The origins of our understanding of the cellular and molecular mechanisms by
      which signaling pathways and downstream transcription factors coordinate the
      specification of adrenocortical cells within the adrenal gland have arisen from
      studies on the role of Sf1 in steroidogenesis and adrenal development initiated
      20 years ago in the laboratory of Dr. Keith Parker. Adrenocortical
      stem/progenitor cells have been predicted to be undifferentiated and quiescent
      cells that remain at the periphery of the cortex until needed to replenish the
      organ, at which time they undergo proliferation and terminal differentiation.
      Identification of these stem/progenitor cells has only recently been explored.
      Recent efforts have examined signaling molecules, including Wnt, Shh, and Dax1,
      which may coordinate intricate lineage and signaling relationships between the
      adrenal capsule (stem cell niche) and underlying cortex (progenitor cell pool) to
      maintain organ homeostasis in the adrenal gland.

PMID- 21094678
TI  - Well differentiated follicular thyroid neoplasia: impact of molecular and
      technological advances on detection, monitoring and treatment.
AB  - Our understanding of the molecular mechanisms responsible for follicular thyroid
      cell oncogenesis has been advanced significantly in recent years. Specific
      genetic alterations and the molecular pathways they affect have been associated
      with particular histologic subtypes of well-differentiated thyroid cancer and are
      now being evaluated for their utility as clinical tools with diagnostic,
      prognostic and even therapeutic relevance. This paper focuses on the most common
      and clinically relevant genetic alterations shown to be consistently associated
      with well-differentiated thyroid carcinoma. We review the impact of recent
      molecular and technological advances on thyroid cancer standard of care and the
      practice of clinical medicine.

PMID- 21094679
TI  - The Wnt/beta-catenin pathway in adrenocortical development and cancer.
AB  - Signaling by the Wnt family of secreted glycolipoproteins plays key roles in
      embryonic development of organisms ranging from nematodes to mammals and is also
      implicated in several types of human cancers. Canonical Wnt signaling functions
      by regulating the translocation of beta-catenin to the nucleus, where it controls
      key gene expression programs through interaction with Tcf/Lef and other families
      of transcription factors. Wnts can also act through non-canonical pathways that
      do not involve beta-catenin activation, but implicate small GTPases/JNK kinase
      and intracellular calcium. Here we review recent studies that have revealed the
      expression of several components of Wnt/beta-catenin signaling in the adrenal
      cortex and discovered a key role for this pathway in the regulation of
      proliferation/differentiation of progenitor cells and in tumorigenesis of that
      endocrine organ.

PMID- 21094680
TI  - A possible role for a paralemniscal auditory pathway in the coding of slow
      temporal information.
AB  - Low-frequency temporal information present in speech is critical for normal
      perception, however the neural mechanism underlying the differentiation of slow
      rates in acoustic signals is not known. Data from the rat trigeminal system
      suggest that the paralemniscal pathway may be specifically tuned to code low
      frequency temporal information. We tested whether this phenomenon occurs in the
      auditory system by measuring the representation of temporal rate in lemniscal and
      paralemniscal auditory thalamus and cortex in guinea pig. Similar to the
      trigeminal system, responses measured in auditory thalamus indicate that slow
      rates are differentially represented in a paralemniscal pathway. In cortex, both
      lemniscal and paralemniscal neurons indicated sensitivity to slow rates. We
      speculate that a paralemniscal pathway in the auditory system may be specifically
      tuned to code low-frequency temporal information present in acoustic signals.
      These data suggest that somatosensory and auditory modalities have parallel sub
      cortical pathways that separately process slow rates and the spatial
      representation of the sensory periphery.

PMID- 21094681
TI  - Korean red ginseng extract ameliorates skin lesions in NC/Nga mice: an atopic
      dermatitis model.
AB  - AIM OF THE STUDY: Korean red ginseng (KRG, Panax ginseng C.A. Meyer) has
      traditionally been considered to harbor anti-allergic effects, however its action
      on atopic dermatitis (AD) is unclear. Therefore, we investigated the effect of
      KRG on AD using NC/Nga mice as an AD model. In addition, we examined the effect
      of aprepitant (substance P specific neurokinin receptor antagonist) on AD.
      MATERIALS AND METHODS: The KRG extract and aprepitant were administered orally to
      NC/Nga mice. The efficacy of KRG and aprepitant was evaluated by assessing total
      clinical severity score, ear thickness, serum IgE level and histology. In
      addition, mRNA and protein expression were measured by real-time RT-PCR and
      immunohistochemistry, respectively. RESULTS: The KRG extract significantly
      reduced the total clinical severity score, ear thickness and the level of serum
      IgE in AD mouse model, whereas aprepitant reduced only the serum IgE level. KRG
      not only decreased TNF-alpha, IFN-gamma and substance P but also reduced the
      infiltration of FOXP3+ regulatory T (Treg) cells and CD1a+ Langerhans cells in
      the lesions, whereas aprepitant decreased only substance P and the infiltration
      of Treg cells. CONCLUSION: These results suggest that KRG extract may be a
      potential therapeutic modality for AD and aprepitant could be used as adjunctive
      agent to control pruritus in AD.

PMID- 21094682
TI  - Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological,
      neural and neuro-immune mechanisms.
AB  - Chronic abdominal pain is a common symptom of great clinical significance in
      several areas of medicine. In many cases no organic cause can be established
      resulting in the classification as functional gastrointestinal disorder.
      Irritable Bowel Syndrome (IBS) is the most common of these conditions and is
      considered an important public health problem because it can be disabling and
      constitutes a major social and economic burden given the lack of effective
      treatments. IBS aetiology is most likely multi-factorial involving biological,
      psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and
      visceral hypervigilance, which could be mediated by peripheral, spinal, and/or
      central pathways, constitute key concepts in current research on
      pathophysiological mechanisms of visceral hyperalgesia. The role of central
      nervous system mechanisms along the "brain-gut axis" is increasingly appreciated,
      owing to accumulating evidence from brain imaging studies that neural processing
      of visceral stimuli is altered in IBS together with long-standing knowledge
      regarding the contribution of stress and negative emotions to symptom frequency
      and severity. At the same time, there is also growing evidence suggesting that
      peripheral immune mechanisms and disturbed neuro-immune communication could play
      a role in the pathophysiology of visceral hyperalgesia. This review presents
      recent advances in research on the pathophysiology of visceral hyperalgesia in
      IBS, with a focus on the role of stress and anxiety in central and peripheral
      response to visceral pain stimuli. Together, these findings support that in
      addition to lower pain thresholds displayed by a significant proportion of
      patients, the evaluation of pain appears to be altered in IBS. This may be
      attributable to affective disturbances, negative emotions in anticipation of or
      during visceral stimulation, and altered pain-related expectations and learning
      processes. Disturbed "top-down" emotional and cognitive pain modulation in IBS is
      reflected by functional and possibly structural brain changes involving
      prefrontal as well as cingulate regions. At the same time, there is growing
      evidence linking peripheral and mucosal immune changes and abdominal pain in IBS,
      supporting disturbed peripheral pain signalling. Findings in post-infectious IBS
      emphasize the interaction between centrally-mediated psychosocial risk factors
      and local inflammation in predicting long-term IBS symptoms. Investigating
      afferent immune-to-brain communication in visceral hyperalgesia as a component of
      the sickness response constitutes a promising future research goal.

PMID- 21094683
TI  - The establishment of an up-scaled micro-mixer method allows the standardized and
      reproducible preparation of well-defined plasmid/LPEI polyplexes.
AB  - Polyplexes based on linear polyethylenimine (LPEI) and plasmid DNA are known as
      efficient non-viral gene delivery systems. However, the requirement for freshly
      prepared complexes prior to administration due to their instability in aqueous
      suspension poses the risk of batch-to-batch variations. Therefore, the aim of the
      study was the establishment of a reproducible and up-scalable method for the
      preparation of well-defined polyplexes. Polyplexes consisting of pCMVLuc plasmid
      and 22 kDa linear polyethylenimine (LPEI) were prepared by classical pipetting or
      with a micro-mixer method using different mixing speeds and plasmid DNA
      concentrations (20-400 MUg/mL). The z-average diameter of the polyplexes was
      measured by dynamic light scattering. Metabolic activity and transfection
      efficiency was evaluated on murine neuroblastoma cells after transfection with
      polyplexes. When varying mixing speeds of the micro-mixer, polyplex size (59-197
      nm) and polydispersity index (0.05-0.19) could be directly controlled. The z
      average diameter (65-170 nm) and polydispersity index (0.05-0.22) of the
      polyplexes increased with increasing plasmid DNA concentration (20-400 MUg/mL).
      The established up-scaled micro-mixer method allows the standardized and
      reproducible preparation of well-defined, transfection-competent plasmid/LPEI
      polyplexes with high reproducibility.

PMID- 21094685
TI  - Quantitative analysis of hemodynamic and metabolic changes in subcortical
      vascular dementia using simultaneous near-infrared spectroscopy and fMRI
      measurements.
AB  - Subcortical vascular dementia (SVD) is a form of vascular dementia from small
      vessel disease with white matter lesions and lacunes. We hypothesized that
      hemodynamic and metabolic changes in the cortex during a simple motor task may
      reflect the impaired neurovascular coupling in SVD. We used fMRI and near
      infrared spectroscopy (NIRS) simultaneously, which together provided multiple
      hemodynamic responses as well as a robust estimation of the cerebral metabolic
      rate of oxygen (CMRO(2)). During the task periods, the oxy-hemoglobin, total
      hemoglobin, blood oxygenation level-dependent (BOLD) response, cerebral blood
      flow (CBF), and CMRO(2) decreased statistically significantly in the primary
      motor and somatosensory cortices of SVD patients, whereas the oxygen extraction
      fraction increased when compared with controls. Notably, the flow-metabolism
      coupling ratio, n representing the ratio of oxygen supply to its utilization,
      showed a robust reduction in the SVD patient group (n(Control)=1.99 +/- 0.23;
      n(SVD)=1.08 +/- 0.24), which implies a loss of metabolic reserve. These results
      support the pathological small vessel compromise, including an increased vessel
      stiffness, impaired vascular reactivity, and impaired neurovascular coupling in
      SVD. In conclusion, simultaneous measurement by NIRS and fMRI can reveal various
      hemodynamic and metabolic changes and may be used for as an early detection or
      monitoring of SVD.

PMID- 21094684
TI  - Exploring the spatial and temporal organization of a cell's proteome.
AB  - To increase our current understanding of cellular processes, such as cell
      signaling and division, knowledge is needed about the spatial and temporal
      organization of the proteome at different organizational levels. These levels
      cover a wide range of length and time scales: from the atomic structures of
      macromolecules for inferring their molecular function, to the quantitative
      description of their abundance, and spatial distribution in the cell. Emerging
      new experimental technologies are greatly increasing the availability of such
      spatial information on the molecular organization in living cells. This review
      addresses three fields that have significantly contributed to our understanding
      of the proteome's spatial and temporal organization: first, methods for the
      structure determination of individual macromolecular assemblies, specifically the
      fitting of atomic structures into density maps generated from electron microscopy
      techniques; second, research that visualizes the spatial distributions of these
      complexes within the cellular context using cryo electron tomography techniques
      combined with computational image processing; and third, methods for the spatial
      modeling of the dynamic organization of the proteome, specifically those methods
      for simulating reaction and diffusion of proteins and complexes in crowded
      intracellular fluids. The long-term goal is to integrate the varied data about a
      proteome's organization into a spatially explicit, predictive model of cellular
      processes.

PMID- 21094686
TI  - Multi-parametric neuroimaging reproducibility: a 3-T resource study.
AB  - Modern MRI image processing methods have yielded quantitative, morphometric,
      functional, and structural assessments of the human brain. These analyses
      typically exploit carefully optimized protocols for specific imaging targets.
      Algorithm investigators have several excellent public data resources to use to
      test, develop, and optimize their methods. Recently, there has been an increasing
      focus on combining MRI protocols in multi-parametric studies. Notably, these have
      included innovative approaches for fusing connectivity inferences with functional
      and/or anatomical characterizations. Yet, validation of the reproducibility of
      these interesting and novel methods has been severely hampered by the limited
      availability of appropriate multi-parametric data. We present an imaging protocol
      optimized to include state-of-the-art assessment of brain function, structure,
      micro-architecture, and quantitative parameters within a clinically feasible 60
      min protocol on a 3-T MRI scanner. We present scan-rescan reproducibility of
      these imaging contrasts based on 21 healthy volunteers (11 M/10 F, 22-61 years
      old). The cortical gray matter, cortical white matter, ventricular cerebrospinal
      fluid, thalamus, putamen, caudate, cerebellar gray matter, cerebellar white
      matter, and brainstem were identified with mean volume-wise reproducibility of
      3.5%. We tabulate the mean intensity, variability, and reproducibility of each
      contrast in a region of interest approach, which is essential for prospective
      study planning and retrospective power analysis considerations. Anatomy was
      highly consistent on structural acquisition (~1-5% variability), while variation
      on diffusion and several other quantitative scans was higher (~<10%). Some
      sequences are particularly variable in specific structures (ASL exhibited
      variation of 28% in the cerebral white matter) or in thin structures
      (quantitative T2 varied by up to 73% in the caudate) due, in large part, to
      variability in automated ROI placement. The richness of the joint distribution of
      intensities across imaging methods can be best assessed within the context of a
      particular analysis approach as opposed to a summary table. As such, all imaging
      data and analysis routines have been made publicly and freely available. This
      effort provides the neuroimaging community with a resource for optimization of
      algorithms that exploit the diversity of modern MRI modalities. Additionally, it
      establishes a baseline for continuing development and optimization of multi
      parametric imaging protocols.

PMID- 21094688
TI  - Anti-IL-23 antibody blockade of IL-23/IL-17 pathway attenuates airway
      obliteration in rat orthotopic tracheal transplantation.
AB  - Obliterative bronchiolitis (OB) has been a major obstacle to long-term allograft
      survival after lung transplantation, and the underlying mechanism is not well
      understood. As IL-23/IL-17 pathway has been shown to play important roles in
      airway inflammation, in this study we have investigated the role of IL-23/IL-17
      pathway in acute and chronic airway allograft rejection. We used a rat OB model
      in orthotopic tracheal transplantation, and investigated the effects of anti-IL
      23 blockade antibody on acute and chronic airway allograft rejection. Anti-IL-23
      antibody impaired the function of IL-23 in inducing IL-17 production. The rats
      that received allografts and treated with anti-IL-23 antibody showed
      significantly less symptom of airway obliteration and chronic transplant
      rejection compared with control rats which received physiological saline or IgG
      antibody. Taken together, our results suggest that anti-IL-23 antibody is
      effective in protecting allograft rejection and the development of chronic OB in
      allo-tracheal transplantation. These findings may have implications for new
      therapies to prevent OB and allograft rejection in human lung transplantation.

PMID- 21094687
TI  - Molecular phylogeny and evolution of symbiosis in a clade of Indopacific
      nudibranchs.
AB  - Previous efforts at understanding the evolution of the genus Phyllodesmium, based
      on morphological analyses, have been plagued by poorly supported phylogenies
      (Ortiz and Gosliner, 2008; Moore and Gosliner, 2009, in press). It has been
      suggested (Moore and Gosliner, 2009) that a molecular phylogeny might provide
      more insight into this history than can be easily discovered using morphological
      data. In this study, 658bp of the cytochrome c oxidase subunit I gene (CO1),
      441bp of the mitochondrial large ribosomal subunit (16S) gene, and 328bp of a
      protein-coding nuclear gene (histone 3) were sequenced for 18 species of
      Phyllodesmium and six outgroup species. A total of 464 parsimony informative
      sites were used for parsimony, maximum likelihood, and Bayesian inference of
      phylogeny analyses. All three analyses produced similar topologies, with the
      exception of a single difference within the parsimony analysis. Bootstrap values
      and posterior probabilities provided strong support at many shallow nodes, and
      the monophyly of Phyllodesmium was supported in every case. Three distinct clades
      of Phyllodesmium are evident in this analysis. One of these represents the
      majority of asymbiotic taxa. Phyllodesmium poindimiei, an asymbiotic species, is
      clearly a member of a symbiotic clade and appears to have secondarily lost its
      symbiotic relationship with zooxanthellae. There was moderate support confirming
      similar topological trends seen in earlier morphological phylogenies, including
      the hypothesis that symbiotic species associating with zooxanthellae have evolved
      more recently than non-symbiotic species. Despite the inclusion of a presumably
      conservative nuclear locus, some deep nodes are still unresolved or are not well
      supported. Future inclusion of additional taxa and more slowly evolving loci will
      likely improve resolution of these deeper nodes. The subsequent phylogeny
      supports previous hypotheses by Rudman (1991), Kempf (1991) and Burghardt et al.
      (2008b) that evolution of more complex digestive gland structures is related to
      increased complexity of symbiosis with zooxanthellae and greater efficiency of
      photosynthetic activity. Our phylogeny also demonstrates that this symbiosis has
      evolved only once in Phyllodesmium and that azooxanthellate species are sister,
      rather than basal, to zooxanthellate species.

PMID- 21094689
TI  - Adoptive transfer of CD4+CD25+ regulatory cells combined with low-dose sirolimus
      and anti-thymocyte globulin delays acute rejection of renal allografts in
      Cynomolgus monkeys.
AB  - Although donor alloantigen specific Treg cells play an important role in
      transplant tolerance, therapeutic applications are limited by their low
      frequency. In this study, isolated Tregs from Cynomolgus monkeys were efficiently
      expanded by a co-culture system, and maintained suppressive function on the
      proliferation of CD4(+) effector cells in vitro. Adoptive transfer of expanded
      donor alloantigen specific Tregs without any immunosuppressants could prolong
      survival of MHC-mismatched allografts in Cynomolgus monkeys. To reach the
      feasibility of clinical transplantation, our objectives focused on whether
      exposure of monkey Tregs to immunosuppressants could preserve suppressive
      function in vitro and in vivo. The results showed that low-dose sirolimus
      selectively expanded Tregs, increased the expression of CD25(bright) and Foxp3
      markers, and suppressed TCR- or allo-antigens induced CD4(+) T cell proliferation
      in vitro. In vivo, after pre-treated with anti-thymocyte globulin (ATG) for
      consecutive 3days, a 14-day therapy of adoptive infusion of donor alloantigen
      specific Tregs combined with low-dose sirolimus delayed acute rejection of renal
      allografts in Cynomolgus monkeys, showing an MST of 48.5days as compared with
      those of untreated and sirolimus-treated monkeys (7days and 22days). The
      frequencies of CD4(+)CD25(bright) T cells were significantly elevated in
      mesenteric lymph nodes vs. those in inguino lymph nodes and peripheral blood. In
      summary, expanded donor alloantigen specific Tregs exposed to sirolimus can
      preserve inhibition in vitro and in vivo. Tregs are more resistant to sirolimus
      than other T cells. Expanded donor alloantigen specific Tregs combined with
      sirolimus and ATG prolongs renal allograft survival in monkeys, suggesting that
      sirolimus might be one of the best synergists for Tregs therapy.

PMID- 21094690
TI  - Identification of small molecular compounds and fabrication of its aqueous
      solution by laser-ablation, expanding primordial cartilage.
AB  - OBJECTIVE: The discovery of small molecular compounds that expand cartilage is
      needed. We searched for small molecular compounds that expand cartilage or
      enhance the actions of bone morphogenetic proteins (BMPs) on cartilage. DESIGN:
      Metatarsal primordial cartilage explants prepared from 14.5 days postcoitum
      (d.p.c.) mouse embryos were organ-cultured in the presence or absence of BMPs
      and/or 4-(5-Benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H-imidazol-2-yl)-benzamide
      hydrate (BPIB) and its related molecules. The perichondrium was removed from some
      of the cartilage explants by partial digestion with collagenase. BPIB aqueous
      solution was prepared by fragmenting BPIB crystals in water with laser
      irradiation and then added to cartilage explants in organ culture. RESULTS: We
      found that small molecular compounds, BPIB, available as SB431542 from Sigma and
      its related molecules, expand primordial cartilage explants in organ culture.
      These molecules are transforming growth factor-beta (TGF-beta) inhibitors, and
      the addition of excess TGF-beta reduced cartilage expansion induced by these
      molecules. The co-administration of BPIB and BMPs synergistically expanded
      cartilage explants. Removal of the perichondrium abolished BIPB-induced cartilage
      expansion but not BMP-induced cartilage-expansion, suggesting that BPIB, but not
      BMPs, expands cartilage through the perichondrium. Furthermore, we used the laser
      ablation technique to generate BPIB aqueous solution in the presence of 2
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) without the use of hazardous
      dimethyl sulfoxide (DMSO). The laser-ablation-generated BPIB aqueous solution was
      more stable, expanded cartilage explants more effectively than BPIB colloidal
      solution prepared with DMSO, and synergistically enhanced BMP-induced cartilage
      expansion. CONCLUSIONS: A small molecular compound, BPIB, expands primordial
      cartilage explants. A BPIB aqueous solution was created by laser-ablation without
      using DMSO and proved to be biologically active.

PMID- 21094691
TI  - Antioxidant diet, gender and age affect renal expression of nitric oxide
      synthases in obese diabetic rats.
AB  - Development of diabetic nephropathy (DN) is associated with decreased renal
      nitric oxide production and increased oxidative stress. We studied nitric oxide
      synthase (NOS) expression in kidney of obese Zucker fa/fa rats, a model of Type 2
      obesity-related DN. Male and female rats received a regular (REG) or antioxidant
      fortified (AO) diet starting at age 4 weeks. Quantitative PCR and immunoblot
      analyses were performed on kidney cortex and medulla to determine levels of
      endothelial, neuronal and inducible NOS at 6, 13 and 20 weeks of age. Multiple
      antibody-specific proteins were detected for each form. These may represent
      monomeric splice forms, post-translationally modified forms and their dimers,
      consistent with the known complexity of regulation of these enzymes. Levels of
      eNOS and nNOS are higher in males than females at 6 weeks on the REG diet and 13
      weeks on either diet; the relationship is reversed in females at 6 weeks on the
      AO diet. Levels of eNOS and nNOS are lower on the AO diet compared to REG, in
      males at 6 and 13 weeks and females at 13 weeks; the reverse is seen in 6 week
      females and 20 week males. All three isoforms show peak levels in the younger
      animals, at 6 or 13 weeks. Better preservation of kidney function is associated
      with higher prevalence of dimers with potential to increase production of NO and
      lower levels of potentially harmful monomers. Differential expression of NOS
      isoforms may be linked to renal functional and histopathological changes in this
      rat model of DN.

PMID- 21094692
TI  - Characteristics of orphan drug applications that fail to achieve marketing
      approval in the USA.
AB  - The US Orphan Drug Act has fostered the development of drugs for patients with
      rare diseases by granting 'orphan designations', although several orphan drugs
      for which a marketing application has been submitted to the FDA have failed to
      obtain approval. This study identified the clinical trial design, the level of
      experience of the sponsor and the level of interaction with the FDA to be
      associated with non-approval. Sponsors, therefore, should engage in dialogue with
      the FDA and thoughtfully design pivotal clinical trials in accordance with FDA
      guidance documents.

PMID- 21094693
TI  - Creativity, innovation and lean sigma: a controversial combination?
AB  - The application of lean sigma is gaining momentum in drug discovery and
      development but it remains controversial because of perceptions that process
      improvement will suppress much-needed creativity and innovation. We review the
      conditions required to support creativity and innovation and the principles and
      benefits of lean sigma in a drug discovery environment. We conclude that it is
      desirable to create a unified climate that encourages and enables both innovation
      and continuous improvement and that this is possible if three key tensions are
      handled carefully and with due respect to the needs of research. These three
      potential traps occur in the interpretation of standardization, the role of
      variation and the choice of how to use liberated capacity.

PMID- 21094694
TI  - Phospholipase-D activity and inflammatory response induced by brown spider
      dermonecrotic toxin: endothelial cell membrane phospholipids as targets for
      toxicity.
AB  - Brown spider dermonecrotic toxins (phospholipases-D) are the most well
      characterized biochemical constituents of Loxosceles spp. venom. Recombinant
      forms are capable of reproducing most cutaneous and systemic manifestations such
      as dermonecrotic lesions, hematological disorders, and renal failure. There is
      currently no direct confirmation for a relationship between dermonecrosis and
      inflammation induced by dermonecrotic toxins and their enzymatic activity. We
      modified a toxin isoform by site-directed mutagenesis to determine if
      phospholipase-D activity is directly related to these biological effects. The
      mutated toxin contains an alanine substitution for a histidine residue at
      position 12 (in the conserved catalytic domain of Loxosceles intermedia
      Recombinant Dermonecrotic Toxin - LiRecDT1). LiRecDT1H12A sphingomyelinase
      activity was drastically reduced, despite the fact that circular dichroism
      analysis demonstrated similar spectra for both toxin isoforms, confirming that
      the mutation did not change general secondary structures of the molecule or its
      stability. Antisera against whole venom and LiRecDT1 showed cross-reactivity to
      both recombinant toxins by ELISA and immunoblotting. Dermonecrosis was abolished
      by the mutation, and rabbit skin revealed a decreased inflammatory response to
      LiRecDT1H12A compared to LiRecDT1. Residual phospholipase activity was observed
      with increasing concentrations of LiRecDT1H12A by dermonecrosis and fluorometric
      measurement in vitro. Lipid arrays showed that the mutated toxin has an affinity
      for the same lipids LiRecDT1, and both toxins were detected on RAEC cell
      surfaces. Data from in vitro choline release and HPTLC analyses of LiRecDT1
      treated purified phospholipids and RAEC membrane detergent-extracts corroborate
      with the morphological changes. These data suggest a phospholipase-D dependent
      mechanism of toxicity, which has no substrate specificity and thus utilizes a
      broad range of bioactive lipids.

PMID- 21094695
TI  - Iron and nitrosative metabolism in the Antarctic mollusc Laternula elliptica.
AB  - The objective of this work was to study Fe distribution, and oxidative and
      nitrosative metabolism in Laternula elliptica for physiological analysis and
      interspecific comparisons. Lipid peroxidation, superoxide dismutase and catalase
      activity and total Fe content were estimated in the digestive glands (DG) of L.
      elliptica. The labile Fe pool (LIP) represents the amount of cellular Fe
      responsible for catalyzing radical-dependent reactions. LIP assessed by the
      calcein assay, represents 3.5% of the total Fe in L. elliptica. Experimental
      isolation of ferritin (Ft) was performed. Subunit analyses of the protein by SDS
      polyacrilamide gel electrophoresis indicated that the protein was composed of
      20.6kDa protein subunits, consistent with the horse spleen Ft and the molecular
      weight markers, however, a higher molecular mass subunit could appear. The
      identity of the protein was confirmed by Western blot analysis. The
      nitrate+nitrite content was 73+/-7pmol/mg fresh mass (FW). The nitric oxide (NO)
      content in DG homogenates, assessed by electronic paramagnetic resonance (EPR)
      spin trapping measurements using the NO trap sodium-N-methyl-D-glucamine
      dithiocarbamate-Fe at room temperature, was 30+/-2pmol/mg FW. Nitric oxide
      synthase-like activity (1.50+/-0.09pmol/mg FW min) was assessed by measuring NO
      production by EPR in the presence of L-arginine (L-A) and NADPH. This activity
      was significantly inhibited by L-A analogs such as Nomega-nitro-L-arginine methyl
      ester hydrochloride (-77%) and Nomega-nitro-L-arginine (-62%), or by the lack of
      added L-A (-55%). The data presented here documented the physiological presence
      of labile Fe, Ft and highly reactive nitrogen species, and are the first evidence
      that support the hypothesis that NO being generated in L. elliptica might
      contribute to restrict oxidative damage by a close link with Fe metabolism.

PMID- 21094696
TI  - Semi-automatic semantic annotation of PubMed queries: a study on quality,
      efficiency, satisfaction.
AB  - Information processing algorithms require significant amounts of annotated data
      for training and testing. The availability of such data is often hindered by the
      complexity and high cost of production. In this paper, we investigate the
      benefits of a state-of-the-art tool to help with the semantic annotation of a
      large set of biomedical queries. Seven annotators were recruited to annotate a
      set of 10,000 PubMed(r) queries with 16 biomedical and bibliographic categories.
      About half of the queries were annotated from scratch, while the other half were
      automatically pre-annotated and manually corrected. The impact of the automatic
      pre-annotations was assessed on several aspects of the task: time, number of
      actions, annotator satisfaction, inter-annotator agreement, quality and number of
      the resulting annotations. The analysis of annotation results showed that the
      number of required hand annotations is 28.9% less when using pre-annotated
      results from automatic tools. As a result, the overall annotation time was
      substantially lower when pre-annotations were used, while inter-annotator
      agreement was significantly higher. In addition, there was no statistically
      significant difference in the semantic distribution or number of annotations
      produced when pre-annotations were used. The annotated query corpus is freely
      available to the research community. This study shows that automatic pre
      annotations are found helpful by most annotators. Our experience suggests using
      an automatic tool to assist large-scale manual annotation projects. This helps
      speed-up the annotation time and improve annotation consistency while maintaining
      high quality of the final annotations.

PMID- 21094698
TI  - Antifibrillatory effect of ranolazine during severe coronary stenosis in the
      intact porcine model.
AB  - BACKGROUND: Clinical evidence suggests that the antianginal agent ranolazine has
      antiarrhythmic properties, but its effects on vulnerability to ventricular
      fibrillation (VF) and T-wave alternans (TWA) during coronary artery stenosis have
      not been measured. OBJECTIVE: We investigated whether the antiarrhythmic effect
      of ranolazine during acute coronary stenosis could be quantified by measuring VF
      threshold and TWA magnitude. METHODS: Electrode catheters placed in the left
      ventricular apex were used to determine VF threshold during ventricular pacing at
      130 beats/min, and TWA was quantified from epicardial electrograms using modified
      moving average method (N = 18). Left anterior descending coronary flow was
      reduced with a balloon occluder by 75% for 10 minutes. The I(Kr) blocker E-4031
      was used to distinguish effects of late I(Na) and I(Kr) inhibition by ranolazine.
      RESULTS: Before stenosis, ranolazine and E-4031 increased VF threshold from 32 +/
      4 mA to 46 +/- 4 mA (mean +/- SEM), P = .02, and from 33 +/- 5 mA to 40 +/- 9
      mA, P = .02, respectively. During stenosis, ranolazine increased VF threshold
      from 19 +/- 2 mA to 33 +/- 3 mA (P = .02), whereas E-4031 decreased VF threshold
      from 21 +/- 3 mA to 15 +/- 3 mA (P = .02). The ischemia-induced increase in TWA
      was suppressed by ranolazine but not by E-4031, consistent with effects of these
      agents on VF threshold. CONCLUSION: Ranolazine exerts significant
      antifibrillatory effects during coronary stenosis through direct effects on
      cardiac electrical properties independent of coronary flow. Ranolazine's
      antifibrillatory action during myocardial ischemia does not appear to be mediated
      by blockade of I(Kr) but rather by inhibition of late I(Na). TWA changes
      paralleled vulnerability to VF as indicated by VF threshold testing.

PMID- 21094699
TI  - Onset dynamics of ventricular tachyarrhythmias as measured by dominant frequency.
AB  - BACKGROUND: Differences in dominant frequency (DF), a measure of electrical
      activation rate, were used to characterize and classify ventricular
      tachyarrhythmias (VTA) at onset. METHOD: In canine 3- to 5-day-old infarct border
      zone, monomorphic re-entrant ventricular tachycardia (MVT) was repeatedly induced
      by programmed electrical stimulation (14 experiments, total of 23 instances used
      for analysis). Ventricular fibrillation (VF) and polymorphic ventricular
      tachycardia (PVT) occasionally occurred (total of 23 and 4 episodes,
      respectively, for all experiments). For each of 196 to 312 border zone bipolar
      electrode recordings, the DF and DF spatial derivative (DFD) were calculated to
      assess electrical activity organization and were used to classify VTAs at onset.
      For classification, measurements were made at 1.5 and 3 seconds from last
      stimulus for all recording sites, and at 2.25 and 3 seconds for 3- to 7-site
      subsets as a test with limited data. RESULTS: At 1.5 seconds after stimulus end,
      the DF/DFD magnitudes were ordered: MVT < PVT < VF (P < .001). DF/DFD trended
      upward in VF, downward in MVT, and lacked trend in PVT (P < .001). Based on
      DF/DFD magnitudes/trends, the MVT/VF classifier accuracy was 94.6% (all sites/1.5
      s), 97.9% (all sites/3 s), 82.6% (subset sites/2.25 s), and 86.3% (subset sites/3
      s). CONCLUSION: VTAs are distinguishable at early onset by degree and trend in
      organization of electrical activity as estimated by DF and DFD. VF becomes
      increasingly disorganized, MVT becomes increasingly organized, and PVT remains
      intermediate. It may be possible to apply this technique for analysis and
      classification in a clinical setting using currently available special mapping
      catheters.

PMID- 21094700
TI  - snail gene expression in the medaka, Oryzias latipes.
AB  - Snail transcription factors have prominent roles during embryonic development of
      vertebrates. They are often involved in cell migration processes during neural
      crest development, epithelial-mesenchymal transition and cancer progression.
      Comparative expression studies of snai gene family members in different
      vertebrate species are expected to contribute to a better understanding of their
      roles during development and reflect their evolutionary history. To investigate
      and to compare the expression patterns of snai genes in a second main fish model
      we used the medaka fish (Oryzias latipes), a complementary teleost model to
      zebrafish. We identified three snai gene family members, snai1a, snai1b and
      snai2. Phylogenetic and synteny analysis show a close relatedness of all family
      members to other vertebrate snai genes. Surprisingly, no homologue of snai3 could
      be identified in medaka, although this gene is present in zebrafish and the
      puffer fishes. Here we demonstrate that while most expression domains of medaka
      snai genes are comparable to zebrafish, the contribution of the individual
      paralogs to the overall pattern differs between the two teleosts and indicate
      lineage specific expression shuffling.

PMID- 21094701
TI  - ANCA in the diagnosis of neutrophil-mediated inflammation.
AB  - Inconsistencies in ANCA (anti-neutrophil cytoplasm autoantibodies) and other NSA
      (neutrophil-specific autoantibodies) terminology frequently cause incorrect
      indications, choices, applications and interpretations of ANCA diagnostics in
      routine practice, except for ANCA-associated vasculitis. A review of the current
      knowledge and the authors' personal experiences based on routine assessments of
      ANCA and other NSA are documented and presented. A better understanding of the
      principles and mechanisms of ANCA and other NSA responses and determination, as
      well as unification of their terminology could result in improvements in
      indications, applications and the interpretation of ANCA diagnostics in diseases
      other than vasculitis, especially in IBD (inflammatory bowel diseases), AILD
      (autoimmune liver diseases), CTD (connective tissue diseases) and other chronic
      neutrophil-mediated inflammatory diseases.

PMID- 21094702
TI  - Regulation of smooth muscle cell phenotype by glycosaminoglycan identity.
AB  - The retention of lipoproteins in the arterial intima is an initial event in early
      atherosclerosis and occurs, in part, through interactions between negatively
      charged glycosaminoglycans (GAGs) and the positively charged residues of
      apolipoproteins. Smooth muscle cells (SMCs) which infiltrate into the lipoprotein
      enriched intima have been observed to transform into lipid-laden foam cells. This
      phenotypic switch is associated with SMC acquisition of a macrophage-like
      capacity to phagocytose lipoproteins and/or of an adipocyte-like capacity to
      synthesize fatty acids de novo. The aim of the present work was to explore the
      impact of GAG identity on SMC foam cell formation using a scaffold environment
      intended to be mimetic of early atherosclerosis. In these studies, we focused on
      chondroitin sulfate C (CSC), dermatan sulfate (DS), and an intermediate molecular
      weight hyaluronan (HAIMW, ~400 kDa), the levels and/or distribution of each of
      which are significantly altered in atherosclerosis. DS hydrogels were associated
      with greater SMC phagocytosis of apolipoprotein B than HAIMW gels. Similarly,
      only SMCs in DS constructs maintained increased expression of the adipocyte
      marker A-FABP relative to HAIMW gels over 35 days of culture. The increased SMC
      foam cell phenotype in DS hydrogels was reflected in a corresponding decrease in
      SMC myosin heavy chain expression in these constructs relative to HAIMW gels at
      day 35. In addition, this DS-associated increase in foam cell formation was
      mirrored in an increased SMC synthetic phenotype, as evidenced by greater levels
      of collagen type I and glucose 6-phosphate dehydrogenase in DS gels than in HAIMW
      gels. Combined, these results support the increasing body of literature that
      suggests a critical role for DS-bearing proteoglycans in early atherosclerosis.

PMID- 21094703
TI  - Decellularization of pericardial tissue and its impact on tensile viscoelasticity
      and glycosaminoglycan content.
AB  - Bovine pericardium is a collagenous tissue commonly used as a natural biomaterial
      in the fabrication of cardiovascular devices. For tissue engineering purposes,
      this xenogeneic biomaterial must be decellularized to remove cellular antigens.
      With this in mind, three decellularization protocols were compared in terms of
      their effectiveness to extract cellular materials, their effect on
      glycosaminoglycan (GAG) content and, finally, their effect on tensile
      biomechanical behavior. The tissue decellularization was achieved by treatment
      with t-octyl phenoxy polyethoxy ethanol (Triton X-100), tridecyl polyethoxy
      ethanol (ATE) and alkaline treatment and subsequent treatment with nucleases
      (DNase/RNase). The quantified residual DNA content (3.0+/-0.4%, 4.4+/-0.6% and
      5.6+/-0.7% for Triton X-100, ATE and alkaline treatment, respectively) and the
      absence of nuclear structures (hematoxylin and eosin staining) were indicators of
      effective cell removal. In the same way, it was found that the native tissue GAG
      content decreased to 61.6+/-0.6%, 62.7+/-1.1% and 88.6+/-0.2% for Triton X-100,
      ATE and alkaline treatment, respectively. In addition, an alteration in the
      tissue stress relaxation characteristics was observed after alkaline treatment.
      We can conclude that the three decellularization agents preserved the collagen
      structural network, anisotropy and the tensile modulus, tensile strength and
      maximum strain at failure of native tissue.

PMID- 21094704
TI  - Langerhans cell histiocytosis, a new clinical phenotype of x-linked
      lymphoproliferative disease?
AB  - Langerhans' cell histiocytosis (LCH) is a rare disease of unkown cause and is
      characterized by clonal proliferation of Langerhans cells. Here, we describe the
      case of a 22-month-old boy with LCH associated with X-linked lymphoproliferative
      disease (XLP). Sequence analysis of SH2D1A for mutations that cause T-cell
      dysfunction revealed a CT substitution at nucleotide 462. This is the first case
      that hints at an association between XLP and LCH.

PMID- 21094705
TI  - Crane-Heise syndrome: two further case reports.
AB  - Crane-Heise syndrome is a rare lethal and autosomal recessive condition which has
      been first reported in 1981 in three siblings presenting intrauterine growth
      retardation, a poorly mineralised calvarium, characteristic facial features
      comprising cleft lip and palate, hypertelorism, anteverted nares, low-set and
      posteriorly rotated ears, vertebral anomalies and absent clavicles. Since then,
      to our knowledge, only one isolated case and two siblings were reported with
      similar findings. We present two further cases, diagnosed after termination of
      pregnancy at 24 weeks' gestation in one case and straight after birth in the
      other, both very similar to the previously reported ones, and broaden the
      clinical spectrum of this entity. To our knowledge, no molecular mechanism has
      been identified in Crane-Heise syndrome so far.

PMID- 21094706
TI  - Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14
      French patients with mental retardation.
AB  - Chromosome 17q21.31 microdeletion was one of the first genomic disorders
      identified by chromosome microarrays. We report here the clinical and molecular
      characterization of a new series of 14 French patients with this microdeletion
      syndrome. The most frequent clinical features were hypotonia, developmental delay
      and facial dysmorphism, but scaphocephaly, prenatal ischemic infarction and
      perception deafness were also described. Genotyping of the parents showed that
      the parent from which the abnormality was inherited carried the H2 inversion
      polymorphism, confirming that the H2 allele is necessary, but not sufficient to
      generate the 17q21.31 microdeletion. Previously reported molecular analyses of
      patients with 17q21.31 microdeletion syndrome defined a 493 kb genomic fragment
      that was deleted in most patients after taking into account frequent copy number
      variations in normal controls, but the deleted interval was significantly smaller
      (205 kb) in one of our patients, encompassing only the MAPT, STH and KIAA1267
      genes. As this patient presents the classical phenotype of 17q21.31 syndrome,
      these data make it possible to define a new minimal critical region of 160.8 kb,
      strengthening the evidence for involvement of the MAPT gene in this syndrome.

PMID- 21094707
TI  - Terminal 4q deletion and 8q duplication in a patient with CHARGE-like features.
AB  - The CHARGE syndrome is a multiple congenital malformation syndrome that usually
      results from deletion or heterozygous loss of function mutations of the
      chromodomain helicase DNA-binding protein 7 (CHD7) gene at 8q12.1. Besides CHD7
      related cases, some patients with CHARGE-like phenotype have been reported with
      chromosomal imbalances. We describe a patient with a pattern of malformations
      reminiscent of CHARGE syndrome: choanal atresia, facial dysmorphism
      (micrognathia, hypertelorism, epicanthic folds, and depressed, broad nasal
      bridge), cardiovascular malformations, cryptorchidism, and developmental delay.
      He had duplication 8q and deletion 4q derived from paternal translocation
      t(4;8)(q34;q22.1). CHD7 mutation or deletion was excluded. The present report to
      the best of our knowledge is the only one describing an unbalanced translocation
      t(4;8) and CHARGE-like phenotype.

PMID- 21094708
TI  - Health services research and how it can inform the current state of
      ophthalmology.

PMID- 21094709
TI  - Cavernous hemangioma of the orbital apex: pathogenetic considerations in surgical
      management.
AB  - PURPOSE: To consider the pathogenesis and growth of cavernous hemangioma,
      particularly within the crowded orbital apex, in decisions regarding surgical
      indications, timing, and technique. DESIGN: A perspective based on analysis of
      the microanatomic relationships and growth potential of apical cavernous
      hemangiomas, with representative case studies illustrating management
      recommendations. METHODS: Analysis of microscopic findings in typical and vision
      loss cases; review of tumor growth patterns as reported in observational and
      interventional studies; consideration of surgical approaches and reported
      functional outcomes. RESULTS: An ongoing, local hemodynamic imbalance may drive
      the proliferation of a cavernous hemangioma. Extension into neighboring tissue
      induces a fibrous capsule, which is continually reconstituted as the lesion
      expands, and which may incorporate visually critical structures in the confines
      of the apex. The extent of this microanatomic intimacy is not detectable
      preoperatively. The tumor's remaining growth potential at the time of diagnosis
      or following incomplete resection is not predictable. CONCLUSIONS: Patients
      without significant vision deficits should be observed for progression. Those
      with significant deficits or signs of progression should be offered timely
      surgery, with recognition of the risks. The surgical approach should be
      individualized based on macroanatomic relationships. The decision to intervene
      should not be a commitment to complete resection at any cost; intraoperative
      recognition of "inoperable" attachments may dictate modifications in order to
      preserve vision.

PMID- 21094710
TI  - Intracameral voriconazole injection in the treatment of fungal endophthalmitis
      resulting from keratitis.

PMID- 21094712
TI  - Submacular choroidal vascular bed watershed zones and their clinical importance.

PMID- 21094714
TI  - Contemporary concepts in the diagnosis of oral and dental disease. Preface.

PMID- 21094715
TI  - The diagnostic process.
AB  - When first case examples presents to a dentist, a patient may have a specific
      complaint, be in need of routine evaluation, or arrive on referral from another
      health care provider. In all cases, proper diagnosis of existing problems is the
      essential first step in provision of appropriate oral health care. The
      clinician's approach to diagnosis and the need to arrive at the appropriate
      diagnosis are daily challenges in dental practice. This article discusses the
      prescriptive and descriptive theories of diagnostic reasoning using 4 case
      examples.

PMID- 21094716
TI  - The influence of systemic diseases on the diagnosis of oral diseases: a problem
      based approach.
AB  - Although all dentists are taught about the importance of oral health to general
      health and that systemic disease can manifest in the oral cavity, the 4-year
      dental school curriculum does not allow time to gain competency in these
      relationships. Nevertheless, all dentists must have skills in taking a medical
      history and an appreciation of oral findings that might have a systemic origin.
      This article focuses on the identification of abnormal signs and symptoms in the
      oral cavity and the determination of those that have a systemic origin. It is
      imperative that clinicians are mindful of the possible oral-systemic
      associations, because these could potentially have a huge impact on patient care.

PMID- 21094717
TI  - Dental caries and pulpal disease.
AB  - This article reviews the diagnostic process, from the first clinically evident
      stages of the caries process to development of pulpal pathosis. The caries
      diagnostic process includes 4 interconnected components-staging caries lesion
      severity, assessing caries lesion activity, and risk assessments at the patient
      and tooth surface level - which modify treatment decisions for the patient.
      Pulpal pathosis is diagnosed as reversible pulpitis, irreversible pulpitis
      (asymptomatic), irreversible pulpitis (symptomatic), and pulp necrosis.
      Periapical disease is diagnosed as symptomatic apical periodontitis, asymptomatic
      apical periodontitis, acute apical abscess, and chronic apical abscess.
      Ultimately, the goal of any diagnosis should be to achieve better treatment
      decisions and health outcomes for the patient.

PMID- 21094718
TI  - Contemporary concepts in the diagnosis of periodontal disease.
AB  - Periodontitis is an inflammatory disease of bacterial origin that results in the
      progressive destruction of the tissues that support the teeth, specifically the
      gingiva, periodontal ligament, and alveolar bone. The diagnosis of periodontal
      disease currently relies almost exclusively on clinical parameters and
      traditional dental radiography. In this article, the authors review current
      diagnostic techniques and present new approaches and technologies that are being
      developed to improve assessment of this common condition.

PMID- 21094719
TI  - Contemporary concepts in the diagnosis of oral cancer and precancer.
AB  - This article addresses several issues in the approach to diagnosis of oral
      cancer. The term oral cancer is clarified. Key aspects of the biologic basis of
      development of oral cancer and the known risk factors associated with the disease
      are summarized. The clinical presentation of oral cancers and precancerous
      lesions and their histopathologic correlates is discussed. The importance of
      conventional tissue biopsy as the prevailing gold standard for diagnosis is
      emphasized. Other current technologies available for detecting and diagnosing
      oral cancer and premalignant lesions are acknowledged, and their respective
      strengths and weaknesses are discussed.

PMID- 21094720
TI  - Autoimmune oral mucosal diseases: clinical, etiologic, diagnostic, and treatment
      considerations.
AB  - This article discusses the classic autoimmune diseases: pemphigus vulgaris,
      mucosal pemphigoid, and oral lichen planus. These are generally considered of
      autoimmune origin or, at a minimum, immune system mediated. Cause, diagnosis, and
      treatment are discussed. As management of these diseases progresses, continued
      advances in molecular pathogenesis will allow insight into which strategies can
      be employed in interfering with the complex cascade of events leading to mucosal
      impairment and clinical morbidity.

PMID- 21094721
TI  - Differential diagnosis of temporomandibular disorders and other orofacial pain
      disorders.
AB  - There are many types of pain conditions that are felt in the orofacial
      structures. Most of the conditions treated by the dentist are associated with the
      teeth, periodontal structures, and associated mucosal tissues. This article
      focuses on the differential diagnosis of other common pain conditions the dentist
      will likely face, such as temporomandibular disorders, neuropathic pain
      disorders, and common headaches; and the clinical presentation of each.
      Controlling or reducing pain can be accomplished by controlling perpetuating
      factors such as parafunctional habits and by some simple behavioral
      modifications. Finally, this article offers some simple treatment considerations.

PMID- 21094722
TI  - Salivary gland disorders.
AB  - Salivary gland abnormalities and salivary dysfunction are important orofacial
      disorders. Patients with such problems are usually seen in the dental office for
      evaluation and therapy, and the dental practitioner is required to make a
      diagnosis and institute care. Therefore, it is necessary for the dentist to be
      knowledgeable regarding the more common pathologic entities that involve the
      salivary apparatus, and also be familiar with the diagnostic and therapeutic
      tools that are available. Successful diagnosis is dependent on the organized
      integration of the information derived from past history, clinical examination,
      salivary volume study, imaging, serology, and histopathologic examination. This
      article discusses the most common disorders seen in the Salivary Gland Center and
      indicates the current approaches to diagnosis. Improvement in diagnostic skills
      will avoid serious complications and lead to specific and effective therapy.

PMID- 21094723
TI  - Imaging technology in implant diagnosis.
AB  - Dental implantology based on osseointegration is among the most significant
      advances in dental science in the last 50 years. Imaging technology contributes
      to all stages of implant treatment, from presurgical site evaluation to
      postoperative assessment of integration, and long-term periodic evaluation of
      implant status. Various imaging modalities have been used for dental implant
      assessment in the different stages of implant treatment. These include intraoral
      radiography (film-based and digital), panoramic radiography, computed tomography,
      cone-beam computed tomography, and others. Selection of the specific imaging
      technique should be based on its suitability for providing the diagnostic
      information required by the implant team at different stages of treatment. This
      article reviews the applications of different imaging technologies and their
      diagnostic contribution to presurgical evaluation, treatment planning, and
      postoperative assessment of dental implants.

PMID- 21094725
TI  - Invited review: A commentary on predictive cheese yield formulas.
AB  - Predictive cheese yield formulas have evolved from one based only on casein and
      fat in 1895. Refinements have included moisture and salt in cheese and whey
      solids as separate factors, paracasein instead of casein, and exclusion of whey
      solids from moisture associated with cheese protein. The General, Barbano, and
      Van Slyke formulas were tested critically using yield and composition of milk,
      whey, and cheese from 22 vats of Cheddar cheese. The General formula is based on
      the sum of cheese components: fat, protein, moisture, salt, whey solids free of
      fat and protein, as well as milk salts associated with paracasein. The testing
      yielded unexpected revelations. It was startling that the sum of components in
      cheese was <100%; the mean was 99.51% (N * 6.31). The mean predicted yield was
      only 99.17% as a percentage of actual yields (PY%AY); PY%AY is a useful term for
      comparisons of yields among vats. The PY%AY correlated positively with the sum of
      components (SofC) in cheese. The apparent low estimation of SofC led to the idea
      of adjusting upwards, for each vat, the 5 measured components in the formula by
      the observed SofC, as a fraction. The mean of the adjusted predicted yields as
      percentages of actual yields was 99.99%. The adjusted forms of the General,
      Barbano, and Van Slyke formulas gave predicted yields equal to the actual yields.
      It was apparent that unadjusted yield formulas did not accurately predict yield;
      however, unadjusted PY%AY can be useful as a control tool for analyses of cheese
      and milk. It was unexpected that total milk protein in the adjusted General
      formula gave the same predicted yields as casein and paracasein, indicating that
      casein or paracasein may not always be necessary for successful yield prediction.
      The use of constants for recovery of fat and protein in the adjusted General
      formula gave adjusted predicted yields equal to actual yields, indicating that
      analyses of cheese for protein and fat may not always be necessary for yield
      prediction. Composition of cheese was estimated using a predictive formula;
      actual yield was needed for estimation of composition. Adjusted formulas are
      recommended for estimating target yields and cheese yield efficiency. Constants
      for solute exclusion, protein-associated milk salts, and whey solids could be
      used and reduced the complexity of the General formula. Normalization of fat
      recovery increased variability of predicted yields.

PMID- 21094724
TI  - Saliva as a diagnostic fluid.
AB  - Salivary diagnostics is a dynamic and emerging field utilizing nanotechnology and
      molecular diagnostics to aid in the diagnosis of oral and systemic diseases. In
      this article the author critically reviews the latest advances using oral
      biomarkers for disease detection. The use of oral fluids is broadening
      perspectives in clinical diagnosis, disease monitoring, and decision making for
      patient care. Important elements determining the future possibilities and
      challenges in this field are also discussed.

PMID- 21094726
TI  - Invited review: The application of alkaline phosphatase assays for the validation
      of milk product pasteurization.
AB  - Standard practices for indirectly assessing the pasteurization status of milk
      products are primarily based on the thermal inactivation kinetics of the
      endogenous milk enzyme, alkaline phosphatase (ALP). This assessment provides an
      invaluable, if not required, tool for both regulatory and in-house process
      control and validation. Endogenous milk ALP manifests a slightly higher heat
      resistance than the pathogenic microflora upon which pasteurization time and
      temperature requirements are based. Hence, ALP activity is recognized and
      accepted as the method of choice for the rapid validation of milk product
      pasteurization. However, ALP assays have notable limitations that must be
      understood if they are to be administered and interpreted correctly and the
      results are to be applied judiciously. Issues such as the reactivation of heat
      denatured ALP and the presence of both heat-stable and -labile microbial ALP are
      addressed. A discussion of ALP in the milk of nonbovine species is presented
      based on the limited literature available. Some discussion of research involving
      alternative pasteurization indicators also is presented. This article is intended
      to summarize the pertinent details of the ALP assay for dairy products (noting
      the basis and limitations of various methods) and the processing, handling, and
      known compositional factors that influence the assay results.

PMID- 21094727
TI  - Kinetic analysis and mathematical modeling of growth and lactic acid production
      of Lactobacillus casei var. rhamnosus in milk whey.
AB  - Lactobacillus casei is a lactic acid bacterium (LAB) that colonizes diverse
      ecological niches and that has found broad commercial application. The aim of
      this study was to characterize the kinetics of biomass production, lactic acid
      production, and substrate consumption of Lactobacillus casei var. rhamnosus
      cultured in deproteinized milk whey. Batch culture experiments were performed in
      an instrumented, 2-L, stirred tank bioreactor using different inoculum
      concentrations (0.5 to 1.0 g/L) and lactose levels (35 to 70 g/L). The time
      series of experimental data corresponding to biomass growth, lactose consumption,
      and lactic acid formation were differentiated to calculate the corresponding
      kinetic rates. Strong exponentially dependent product inhibition effects were
      evident at low lactic acid concentrations, and lactic acid production rate was
      partially associated with biomass growth. A mathematical model is presented that
      reproduces the experimental lactose, biomass, and lactic acid concentration
      profiles.

PMID- 21094728
TI  - Heat stability of reconstituted, protein-standardized skim milk powders.
AB  - We determined the effects of standardization material, protein content, and pH on
      the heat stability of reconstituted milk made from low-heat (LH) and medium-heat
      (MH) nonfat dry milk (NDM). Low-heat and MH NDM were standardized downward from
      35.5% to 34, 32, and 30% protein by adding either edible lactose powder (ELP) or
      permeate powder (PP) from skim milk ultrafiltration. These powders were called
      standardized skim milk powders (SSMP). The LH and MH NDM and SSMP were
      reconstituted to 9% total solids. Furthermore, subsamples of reconstituted NDM
      and SSMP samples were set aside to measure heat stability at native (unadjusted)
      pH, and the rest were adjusted to pH 6.3 to 7.0. Heat stability is defined as
      heat coagulation time at 140 degrees C of the reconstituted LH or MH NDM and SSMP
      samples. The entire experiment was replicated 3 times at unadjusted pH values and
      2 times at adjusted pH values. At an unadjusted pH, powder type, standardization
      material, and protein content influenced the heat stability of the samples. Heat
      stability for reconstituted LH NDM and SSMP was higher than reconstituted MH NDM
      and SSMP. Generally, decreased heat stability was observed in reconstituted LH or
      MH SSMP as protein content was decreased by standardization. However, adding ELP
      to MH SSMP did not significantly change its heat stability. When pH was adjusted
      to values between 6.3 and 7.0, powder type, standardization material, and pH had
      a significant effect on heat stability, whereas protein content did not. Maximum
      heat stability was noted at pH 6.7 for both reconstituted LH NDM and SSMP
      samples, and at pH 6.6 for both reconstituted MH NDM and SSMP samples.
      Furthermore, for samples with adjusted pH, higher heat stability was observed for
      reconstituted LH SSMP containing PP compared with reconstituted milk from LH SSMP
      containing ELP. However, no statistical difference was observed in the heat
      stability of reconstituted milk from MH NDM and MH SSMP samples. We conclude that
      powder type (LH or MH) and effect of standardization material (ELP or PP) can
      help explain differences in heat stability. The difference in the heat stability
      of powder type may be associated with the difference in the pH of maximum heat
      stability and compositional differences in the standardization material (ELP or
      PP).

PMID- 21094729
TI  - Chemical characterization of the oligosaccharides in Bactrian camel (Camelus
      bactrianus) milk and colostrum.
AB  - Bactrian camel milk and colostrum are commonly used as foods in Mongolia, whose
      people believe that these products promote human health. It has been hypothesized
      that milk oligosaccharides are biologically significant components of human milk,
      acting as receptor analogs that inhibit the attachment of pathogenic
      microorganisms to the colonic mucosa, and as prebiotics, which stimulate the
      growth of bifidobacteria within the infant colon. To evaluate their biological
      significance, we studied the oligosaccharides present in samples of Bactrian
      camel milk and colostrum. Using (1)H-nuclear magnetic resonance spectroscopy, we
      identified and characterized the following oligosaccharides of camel colostrum:
      Gal(beta1-4)[Fuc(alpha1-3)]Glc (3-fucosyllactose), Gal(beta1-3)Gal(beta1-4)Glc
      (3'-galactosyllactose), Gal(beta1-6)Gal(beta1-4)Glc (6'-galactosyllactose),
      Neu5Ac(alpha2-3)Gal(beta1-4)Glc (3'-sialyllactose), Neu5Ac(alpha2-6)Gal(beta1
      4)Glc (6'-sialyllactose), Neu5Ac(alpha2-3)Gal(beta1-3)Gal(beta1-4)Glc (sialyl-3'
      galactosyllactose), Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc
      (sialyllacto-N-tetraose c), Neu5Ac(alpha2-3)Gal(beta1-3)[Gal(beta1-4)GlcNAc(beta1
      6)]Gal(beta1-4)Glc (sialyllacto-N-novopentaose a), Gal(beta1-3)[Neu5Ac(alpha2
      6)Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (sialyllacto-N-novopentaose b); and
      Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1
      4)Glc (monosialyllacto-N-neohexaose). The oligosaccharides in the mature camel
      milk were characterized as 3'-galactosyllactose, Gal(beta1-3)[Gal(beta1
      4)GlcNAc(beta1-6)]Gal(beta1-4)Glc (lacto-N-novopentaose I), and 3'-sialyllactose.

PMID- 21094730
TI  - Micellar casein concentrate production with a 3X, 3-stage, uniform transmembrane
      pressure ceramic membrane process at 50 degrees C.
AB  - The production of serum protein (SP) and micellar casein from skim milk can be
      accomplished using microfiltration (MF). Potential commercial applications exist
      for both SP and micellar casein. Our research objective was to determine the
      total SP removal and SP removal for each stage, and the composition of retentates
      and permeates, for a 3*, continuous bleed-and-feed, 3-stage, uniform
      transmembrane pressure (UTP) system with 0.1-MUm ceramic membranes, when
      processing pasteurized skim milk at 50 degrees C with 2 stages of water
      diafiltration. For each of 4 replicates, about 1,100 kg of skim milk was
      pasteurized (72 degrees C, 16s) and processed at 3* through the UTP MF system.
      Retentate from stage 1 was cooled to <4 degrees C and stored until the next
      processing day, when it was diluted with reverse osmosis water back to a 1*
      concentration and again processed through the MF system (stage 2) to a 3*
      concentration. The retentate from stage 2 was stored at <4 degrees C, and, on the
      next processing day, was diluted with reverse osmosis water back to a 1*
      concentration, before running through the MF system at 3* for a total of 3
      stages. The retentate and permeate from each stage were analyzed for total
      nitrogen, noncasein nitrogen, and nonprotein nitrogen using Kjeldahl methods;
      sodium dodecyl sulfate-PAGE analysis was also performed on the retentates from
      each stage. Theoretically, a 3-stage, 3* MF process could remove 97% of the SP
      from skim milk, with a cumulative SP removal of 68 and 90% after the first and
      second stages, respectively. The cumulative SP removal using a 3-stage, 3* MF
      process with a UTP system with 0.01-MUm ceramic membranes in this experiment was
      64.8 +/- 0.8, 87.8 +/- 1.6, and 98.3 +/- 2.3% for the first, second, and third
      stages, respectively, when calculated using the mass of SP removed in the
      permeate of each stage. Various methods of calculation of SP removal were
      evaluated. Given the analytical limitations in the various methods for measuring
      SP removal, calculation of SP removal based on the mass of SP in the skim milk
      (determined by Kjeldahl) and the mass SP present in all of the permeate produced
      by the process (determined by Kjeldahl) provided the best estimate of SP removal
      for an MF process.

PMID- 21094731
TI  - Camembert-type cheese ripening dynamics are changed by the properties of wrapping
      films.
AB  - Four gas-permeable wrapping films exhibiting different degrees of water
      permeability (ranging from 1.6 to 500 g/m(2) per d) were tested to study their
      effect on soft-mold (Camembert-type) cheese-ripening dynamics compared with
      unwrapped cheeses. Twenty-three-day trials were performed in 2 laboratory-size
      (18L) respiratory-ripening cells under controlled temperature (6 +/- 0.5 degrees
      C), relative humidity (75 +/- 2%), and carbon dioxide content (0.5 to 1%). The
      films allowed for a high degree of respiratory activity; no limitation in gas
      permeability was observed. The wide range of water permeability of the films led
      to considerable differences in cheese water loss (from 0.5 to 12% on d 23,
      compared with 15% for unwrapped cheeses), which appeared to be a key factor in
      controlling cheese-ripening progress. A new relationship between 2 important
      cheese-ripening descriptors (increase of the cheese core pH and increase of the
      cheese's creamy underrind thickness) was shown in relation to the water
      permeability of the wrapping film. High water losses (more than 10 to 12% on d
      23) also were observed for unwrapped cheeses, leading to Camembert cheeses that
      were too dry and poorly ripened. On the other hand, low water losses (from 0.5 to
      1% on d 23) led to over-ripening in the cheese underrind, which became runny as a
      result. Finally, water losses from around 3 to 6% on d 23 led to good ripening
      dynamics and the best cheese quality. This level of water loss appeared to be
      ideal in terms of cheese-wrapping film design.

PMID- 21094732
TI  - Proteomic and peptidomic study of proteolysis in quarter milk after infusion with
      lipoteichoic acid from Staphylococcus aureus.
AB  - Mastitic milk is associated with increased bovine protease activity, such as that
      from plasmin and somatic cell enzymes, which cause proteolysis of the caseins and
      may reduce cheese yield and quality. The aim of this work was to characterize the
      peptide profile resulting from proteolysis in a model mastitis system and to
      identify the proteases responsible. One quarter of each of 2 cows (A and B) was
      infused with lipoteichoic acid from Staphylococcus aureus. The somatic cell
      counts of the infused quarters reached a peak 6h after infusion, whereas plasmin
      activity of those quarters also increased, reaching a peak after 48 and 12h for
      cow A and B, respectively. Urea-polyacrylamide gel electrophoretograms of milk
      samples of cow A and B obtained at different time points after infusion and
      incubated for up to 7 d showed almost full hydrolysis of beta- and alpha(S1)
      casein during incubation of milk samples at peak somatic cell counts, with that
      of beta-casein being faster than that of alpha(S1)-casein. Two-dimensional gel
      electrophoretograms of milk 6h after infusion with the toxin confirmed hydrolysis
      of beta- and alpha(S1)-casein and the appearance of lower-molecular-weight
      products. Peptides were subsequently separated by reversed-phase HPLC and
      handmade nanoscale C(18) columns, and identified by matrix-assisted laser
      desorption/ionization time-of-flight tandem mass spectrometry. Twenty different
      peptides were identified and shown to originate from alpha(s1)- and beta-casein.
      Plasmin, cathepsin B and D, elastase, and amino- and carboxypeptidases were
      suggested as possible responsible proteases based on the peptide cleavage sites.
      The presumptive activity of amino- and carboxypeptidases is surprising and may
      indicate the activity of cathepsin H, which has not been reported in milk
      previously.

PMID- 21094733
TI  - In vitro screening of lactobacilli with antagonistic activity against
      Helicobacter pylori from traditionally fermented foods.
AB  - Helicobacter pylori may cause stomach diseases such as chronic gastritis, peptic
      ulcer, and gastric cancer, and several studies reported that lactobacilli have
      inhibitory effects on H. pylori. In this study, 38 Lactobacillus strains were
      screened for anti-H. pylori activity using in vitro methods, including
      survivability under the simulated gastric conditions, agar plate diffusion,
      urease activity, coaggregation, autoaggregation, and hydrocarbon analysis. The
      results indicate that 2 Lactobacillus strains showed potential anti-H. pylori
      activity in vitro. Lactobacillus plantarum 18 had the largest zone of inhibition
      and markedly reduced the urease activity of H. pylori. Lactobacillus gasseri Chen
      had higher coaggregation rate (58.15%) and hydrophobicity (59.27%) compared with
      the other strains. Further research is needed to verify the activities of these
      strains against H. pylori.

PMID- 21094734
TI  - Assessing the effects of severe heat treatment of milk on calcium
      bioavailability: in vitro and in vivo studies.
AB  - Thermal processing of milk is a common practice. As milk is the main source of
      dietary calcium, this study aimed to assess the effects of overheating milk on
      calcium availability. Thus, thermally damaged milk (overheated, OH, milk; 3
      cycles of sterilization at 116  degrees C, 16 min) was compared with UHT milk
      (150  degrees C, 6s) in 2 types of assays: in vitro and in vivo (rats). In
      addition, the greater Maillard reaction rate associated with thermal treatment in
      OH milk was confirmed by determining specific (furosine) and unspecific markers
      (CieLab color). A negative effect on calcium solubility was observed after in
      vitro digestion of OH milk compared with UHT milk. Feeding rats the diet
      containing OH milk as the protein source led to significantly lower values of
      apparent calcium absorption and retention than those found among animals fed the
      UHT milk diet. Whereas reducing the absorption appears to result mainly from the
      decreased food intake, the negative effect on retention seems to be due to
      factors derived from milk thermal damage, such as the formation of Maillard
      reaction products. It was concluded that milk-processing conditions warrant
      special attention to prevent impaired dietary calcium utilization. This may be
      especially important in situations where milk and dairy products are the main
      dietary components, such as in early infancy.

PMID- 21094735
TI  - Evaluation of a microbiological indicator test for antibiotic detection in ewe
      and goat milk.
AB  - Antibiotics are widely used for therapeutic and prophylactic purposes in dairy
      animals. The presence of residual antibiotics in milk could cause potentially
      serious problems in human health and have technological implication in the
      manufacturing of dairy products. The aim of this study was to evaluate Delvotest
      Accelerator (DSM Food Specialties, Delft, the Netherlands), a new system for a
      fully automated microbial test to detect antibiotic residues in ewe and goat
      milk. Forty-three samples of raw, whole, refrigerated bulk-tank milk samples (22
      of ewe milk and 21 of goat milk) were analyzed during the whole lactation period.
      Four concentrations of 4 antibiotics were diluted in milk: penicillin G at 1, 2,
      3, and 4 MUg/L; sulfadiazine at 25, 50, 100, and 200 MUg/L; tetracycline at 50,
      100, 200, and 400 MUg/L; and gentamicin at 25, 50, 100, and 200 MUg/L. The
      detection limit of the Delvotest Accelerator was calculated as the range of
      antibiotic concentrations within which 95% of positive result lie. The range of
      detection limit of penicillin G and sulfadiazine was easily detected by Delvotest
      Accelerator at or below the European Union maximum residue limits, both for ewe
      and goat milk samples. In contrast, the system showed a lower ability to detect
      tetracycline and gentamicin both for ewe and goat milk samples. Very low
      percentages of false-positive outcomes were obtained. Lactation phase did not
      seem to be a crucial factor affecting the ability of the Delvotest Accelerator to
      detect spiked milk samples. A higher detection ability was observed for goat milk
      samples compared with ewe milk samples. A negative correlation between the
      percentage of positive milk samples detected and milk fat, protein, and lactose
      contents was observed for gentamicin only.

PMID- 21094736
TI  - Fourier transform infrared spectroscopy and multivariate analysis for the
      detection and quantification of different milk species.
AB  - The authenticity of milk and milk products is important and has extended health,
      cultural, and financial implications. Current analytical methods for the
      detection of milk adulteration are slow, laborious, and therefore impractical for
      use in routine milk screening by the dairy industry. Fourier transform infrared
      (FT-IR) spectroscopy is a rapid biochemical fingerprinting technique that could
      be used to reduce this sample analysis period significantly. To test this
      hypothesis we investigated 3 types of milk: cow, goat, and sheep milk. From
      these, 4 mixtures were prepared. The first 3 were binary mixtures of sheep and
      cow milk, goat and cow milk, or sheep and goat milk; in all mixtures the mixtures
      contained between 0 and 100% of each milk in increments of 5%. The fourth
      combination was a tertiary mixture containing sheep, cow, and goat milk also in
      increments of 5%. Analysis by FT-IR spectroscopy in combination with multivariate
      statistical methods, including partial least squares (PLS) regression and
      nonlinear kernel partial least squares (KPLS) regression, were used for
      multivariate calibration to quantify the different levels of adulterated milk.
      The FT-IR spectra showed a reasonably good predictive value for the binary
      mixtures, with an error level of 6.5 to 8% when analyzed using PLS. The results
      improved and excellent predictions were achieved (only 4-6% error) when KPLS was
      employed. Excellent predictions were achieved by both PLS and KPLS with errors of
      3.4 to 4.9% and 3.9 to 6.4%, respectively, when the tertiary mixtures were
      analyzed. We believe that these results show that FT-IR spectroscopy has
      excellent potential for use in the dairy industry as a rapid method of detection
      and quantification in milk adulteration.

PMID- 21094737
TI  - Short communication: Identification of subclinical cow mastitis pathogens in milk
      by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Subclinical mastitis is a common and easily disseminated disease in dairy herds.
      Its routine diagnosis via bacterial culture and biochemical identification is a
      difficult and time-consuming process. In this work, we show that matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)
      allows bacterial identification with high confidence and speed (1 d for bacterial
      growth and analysis). With the use of MALDI-TOF MS, 33 bacterial culture isolates
      from milk of different dairy cows from several farms were analyzed, and the
      results were compared with those obtained by classical biochemical methods. This
      proof-of-concept case demonstrates the reliability of MALDI-TOF MS bacterial
      identification, and its increased selectivity as illustrated by the additional
      identification of coagulase-negative Staphylococcus species and mixed bacterial
      cultures. Matrix-assisted laser desorption-ionization mass spectrometry
      considerably accelerates the diagnosis of mastitis pathogens, especially in cases
      of subclinical mastitis. More immediate and efficient animal management
      strategies for mastitis and milk quality control in the dairy industry can
      therefore be applied.

PMID- 21094738
TI  - Hot topic: Successful fixed-time insemination within 21 d after first
      insemination by combining chemical pregnancy diagnosis on d 18 with a rapid
      resynchronization program.
AB  - Cattle that are not pregnant to first fixed-time artificial insemination (TAI)
      may be resynchronized for a second TAI if they are found nonpregnant at pregnancy
      diagnosis. The specific interval between first and second TAI ranges from 4 to 8
      wk. The selected interval depends on the available method of pregnancy diagnosis
      and the efficiency of the resynchronization program. The objective of this
      experiment was to evaluate a pregnancy diagnosis and resynchronization system
      that achieved a 21-d interval between TAI. This 21-d interval approximates the
      natural return-to-service interval. It also enables resynchronization to be
      implemented within the same estrous cycle in which cattle are first inseminated.
      Holstein heifers were randomly assigned to a 21-d resynchronization program
      (21d_resynch; n = 40) or a control group in which estrus was observed for the
      purpose of re-insemination (control; n = 29). The 21d_resynch heifers were
      diagnosed for pregnancy on d 18 after a TAI (d 0) by using predetermined cut-off
      values for 2'-5' oligoadenylate synthetase 1 (Oas1) gene expression in leukocytes
      and plasma progesterone concentration. Heifers that were not pregnant to first
      TAI had greater expression of Oas1 at the time of PGF(2alpha) (d -3) than
      pregnant heifers, but this relationship was reversed on d 18 after TAI: the
      heifers that were pregnant to first TAI had almost 5-fold greater expression of
      Oas1 compared with nonpregnant heifers. Nonpregnant heifers in the 21d_resynch
      group were injected with a luteolytic dose of PGF(2alpha) on d 19 and were
      injected with GnRH on d 21 and submitted to TAI. The pregnancy per AI after first
      insemination was similar for 21d_resynch (50.0%; pregnancy diagnosis on d 18) and
      control (51.7%; pregnancy diagnosis on d 27). Likewise, no difference was
      detected in second insemination pregnancy per AI for 21d_resynch (36.8%;
      nonpregnant heifers TAI on d 21) and control (35.7%; nonpregnant heifers
      inseminated at return to estrus or after nonpregnant diagnosis on d 27). The
      interval between first and second insemination was shorter for 21d_resynch
      compared with control (21.0 +/- 0 and 27.5 +/- 2.1 d). The conclusion is that a
      TAI resynchronization can be programmed within 21 d of previous TAI when a d 18
      pregnancy test and a rapid resynchronization are used.

PMID- 21094739
TI  - Fresh cow mastitis monitoring on day 3 postpartum and its relationship to
      subsequent milk production.
AB  - The purpose was to determine the association of milk California Mastitis Test
      (CMT), somatic cell concentration (SCC), and milk differential cell count results
      on day 3 postcalving with subsequent lactation production and health events. On d
      3 postcalving, the CMT was performed and quarter milk samples were collected from
      130 dairy cows. Quarter SCC and milk differential cell counts were determined.
      Microbiology on duplicate quarter milk samples was used to determine the presence
      of intramammary infection by major or minor pathogens. Production measures
      obtained using Dairy Herd Improvement Association testing were 150-d standardized
      and summit milks. Milk culture results on a cow basis included 82 (63.1%) samples
      with no growth, 31 (23.9%) with major pathogens, and 17 (13.1%) with minor
      pathogens. Milk culture results comparing cows with no growth to those with any
      growth (major or minor pathogens) were not associated with statistically
      significant differences in milk production. Milk culture results comparing cows
      with major pathogens to those with no growth and minor pathogens combined were
      associated with statistically significant differences in 150 d milk. Milk
      production did not differ for cows with CMT results above and below a cut-off of
      trace, and for SCC results above and below cut-offs of 200,000, 300,000, and
      400,000/mL, respectively. Statistically significant differences in milk
      production were found for cows above and below cut-offs for percentage
      neutrophils in milk and for absolute neutrophil counts. Associations were found
      for milk production and number of quarters (0, 1, 2, or 3 and 4 combined) above
      respective cut-offs for SCC, percentage neutrophils in milk, and absolute numbers
      of neutrophils in milk, but not for CMT. Milk production differed for cows
      experiencing any health event versus those with no health event. The most
      commonly recorded health event was clinical mastitis. Statistically significant
      associations were detected between health events and milk culture results, SCC,
      neutrophil percentage, and neutrophil absolute counts. Results of the present
      investigation indicate that milk monitoring on d 3 of lactation using milk
      neutrophil percentage or neutrophil absolute counts may be useful as an
      indication of subsequent milk production.

PMID- 21094740
TI  - Vitamin E supplementation during the dry period in dairy cattle. Part I: adverse
      effect on incidence of mastitis postpartum in a double-blind randomized field
      trial.
AB  - A randomized, controlled field trial with dairy cows demonstrated an adverse
      effect of vitamin E supplementation during the dry period on mastitis incidence
      in early lactation. This study was conducted on farms with historically high
      rates of mastitis to investigate the benefit of vitamin E supplementation on
      udder health; however, the outcome showed an adverse effect. The aim of the study
      was to evaluate whether daily supplementation of 3,000 IU of vitamin E to dairy
      cows during the dry period could improve udder health in commercial herds with a
      high incidence of mastitis. On 5 dairy farms, dry cows were randomly divided into
      2 experimental groups: a high and a low group. Both groups received a dry cow
      mineral mix providing 3,000 or 135 IU of vitamin E/cow per day, respectively,
      between dry-off and calving for a mean period of 8 wk. Providing 3,000 IU of
      vitamin E exceeds NRC standards, but this amount has been used in previous
      studies. The experiment, as well as the majority of the statistical analysis,
      were carried out blinded. Blood was sampled 3 times before calving and on calving
      day. Serum was analyzed for vitamin E and cholesterol. Vitamin E and the vitamin
      E:cholesterol ratio were analyzed as dependent variables in mixed models and
      Student's t-tests to study trends in time and differences between groups.
      Relative risk calculation and survival analysis were used to study the effect of
      supplementation on mastitis incidence in the first 3 mo of lactation. The results
      showed that vitamin E supplements increased both absolute vitamin E and the ratio
      of vitamin E to cholesterol in blood. In the high group, significantly more
      subclinical and clinical cases occurred, showing the same trend on all farms. In
      this study, an initial vitamin E level at dry off above 14.5 MUmol/L was a risk
      factor for clinical mastitis, suggesting that the vitamin E status at the start
      of the dry period is important. It is recommended to work out exactly at what
      threshold vitamin E is harmful for udder health before new trials with high
      dosages of vitamin E are started. Additionally, further research is required to
      investigate the mechanism by which vitamin E affects udder health.

PMID- 21094741
TI  - Vitamin E supplementation during the dry period in dairy cattle. Part II:
      oxidative stress following vitamin E supplementation may increase clinical
      mastitis incidence postpartum.
AB  - The aim of this study was to evaluate, retrospectively, which physiological
      states influenced the effect of vitamin E supplements during the dry period on
      the level of oxidative stress at 2 wk antepartum. Furthermore the effect of
      oxidative stress at 2 wk antepartum on the risk of clinical mastitis in early
      lactation was investigated. Cows experience oxidative stress around calving.
      Vitamin E is able to decrease oxidative stress by scavenging free radicals.
      Normally, vitamin E radicals formed when vitamin E reacts with free radicals are
      regenerated by a network of other antioxidants, termed the "vitamin E
      regeneration system" (VERS). In case of vitamin E supplementation, VERS should be
      sufficient to regenerate formed vitamin E radicals; if not, oxidative stress
      might increase instead of decrease. Additionally, the level of oxidative stress
      and vitamin E might be important physiological states to evaluate before
      supplementation. In a clinical trial, 296 cows on 5 farms were randomly divided
      into 2 groups, supplemented with a mineral mix between dry off and calving that
      supplied 3,000 or 135 IU/d, respectively. Blood samples collected at dry off and
      2 wk antepartum were analyzed for vitamin E, reactive oxygen metabolites, ferric
      reducing ability of plasma, glutathione peroxidase, and malondialdehyde. Cows
      were allocated retrospectively into 8 subgroups based on the level of oxidative
      stress, vitamin E, and VERS status at dry off. To evaluate whether differences in
      physiological states at dry off influenced the effect of vitamin E
      supplementation on the level of oxidative stress, group effects (supplemented vs.
      control) were studied with Student's t-test for all 8 subgroup at 2 wk
      antepartum. Differences in physiological states at dry off influenced the effect
      of vitamin E supplements. In 2 insufficient VERS subgroups, the supplemented
      group had higher levels of free radicals at 2 wk antepartum compared with the
      control group. Relative risk calculation was used to study the effect of
      oxidative stress at 2 wk antepartum on the incidence of mastitis in the first 100
      d of lactation. Higher levels of oxidative stress at 2 wk antepartum were related
      to higher risk of clinical mastitis. In conclusion, not every dry cow responded
      well to high vitamin E supplementation. This subgroup analysis provides a
      possible explanation for the unexpected adverse effects observed in the clinical
      trial.

PMID- 21094742
TI  - Field comparison of real-time polymerase chain reaction and bacterial culture for
      identification of bovine mastitis bacteria.
AB  - Fast and reliable identification of the microorganisms causing mastitis is
      important for management of the disease and for targeting antimicrobial
      treatment. Methods based on PCR are being used increasingly in mastitis
      diagnostics. Comprehensive field comparisons of PCR and traditional milk
      bacteriology have not been available. The results of a PCR kit capable of
      detecting 11 important etiological agents of mastitis directly from milk in 4h
      were compared with those of conventional bacterial culture (48h). In total, 1,000
      quarter milk samples were taken from cows with clinical or subclinical mastitis,
      or from clinically healthy quarters with low somatic cell count (SCC). Bacterial
      culture identified udder pathogens in 600/780 (77%) of the clinical samples,
      whereas PCR identified bacteria in 691/780 (89%) of the clinical samples. The PCR
      analysis detected major pathogens in a large number of clinical samples that were
      negative for the species in culture. These included 53 samples positive for
      Staphylococcus aureus by PCR, but negative by culture. A total of 137 samples
      from clinical mastitis, 5 samples from subclinical mastitis, and 1 sample from a
      healthy quarter were positive for 3 or more bacterial species in PCR, whereas
      culture identified 3 or more species in 60 samples from clinical mastitis.
      Culture identified a species not targeted by the PCR test in 44 samples from
      clinical mastitis and in 9 samples from subclinical mastitis. Low SCC samples
      provided a small number of positive results both in culture (4/93; 4.3%) and by
      PCR (7/93; 7.5%). In conclusion, the PCR kit provided several benefits over
      conventional culture, including speed, automated interpretation of results, and
      increased sensitivity. This kit holds much promise as a tool to complement
      traditional methods in identification of pathogens. In conventional mastitis
      bacteriology, a sample with 3 or more species is considered contaminated, and
      resampling of the cow is recommended. Further study is required to investigate
      how high sensitivity of PCR and its quantitative features can be applied to
      improve separation of relevant udder pathogens from likely contaminants in
      samples where multiple species are detected. Furthermore, increasing the number
      of species targeted by the PCR test would be advantageous.

PMID- 21094743
TI  - Somatic cell counts and bacteriological status in quarter foremilk samples of
      cows in Hesse, Germany--a longitudinal study.
AB  - Somatic cell counts (SCC) are generally used as an indicator of udder health.
      Currently in Germany, 100,000 cells/mL is the threshold differentiating infected
      and noninfected mammary glands. The aim of our study was the detailed analysis of
      udder health in a representative part of the dairy cow population in Hesse,
      Germany. Between 2000 and 2008, 615,187 quarter foremilk samples were analyzed.
      In addition to evaluation of distribution of SCC and prevalence of mastitis
      pathogens, pathogen prevalence was also calculated depending on SCC. The data
      indicated that 38% of all samples had SCC >100,000 cells/mL and 62% showed SCC <=
      100,000 cells/mL; 31% of all samples revealed SCC <= 25,000 cells/mL. Coagulase
      negative staphylococci were the dominant pathogens in the Hessian quarter
      foremilk samples (17.17% of all samples) followed by Corynebacterium spp.
      (13.56%), Streptococcus uberis (8.7%), and Staphylococcus aureus (5.01%).
      Mastitis pathogens were detected in 83% of all samples with SCC >100,000
      cells/mL. However, the prevalence of mastitis pathogens in the SCC range from
      1,000 to <= 100,000 cells/mL was 8.5% (5.51% minor pathogens, 2.01% major
      pathogens, and 0.98% other pathogens). For farms producing high quality milk,
      exceptional hygiene management is compulsory. One of the farms randomly selected
      showed clearly different results from the Hessian survey. Fifteen percent more
      samples lay in the SCC range <= 100,000 cells/mL with a lower prevalence of
      mastitis pathogens of 1.91% (1.03% minor pathogens, 0.83% major pathogens, and
      0.05% other pathogens). Based on these results, inflammatory processes can
      obviously be detected in mammary glands of udder quarters healthy according to
      the current definitions. However, we argue that such inflammation can be detected
      by examination of the relationship of immune cells in milk.

PMID- 21094744
TI  - Effect of abomasal glucose infusion on plasma concentrations of gut peptides in
      periparturient dairy cows.
AB  - Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters
      in the portal vein, hepatic vein, mesenteric vein, and an artery were used to
      study the effects of abomasal glucose infusion on splanchnic plasma
      concentrations of gut peptides. The experimental design was a randomized block
      design with repeated measurements. Cows were assigned to one of 2 treatments:
      control or infusion of 1,500 g of glucose/d into the abomasum from the day of
      parturition to 29 d in milk. Cows were sampled 12 +/- 6 d prepartum and at 4, 15,
      and 29 d in milk. Concentrations of glucose-dependent insulinotropic polypeptide,
      glucagon-like peptide 1(7-36) amide, and oxyntomodulin were measured in pooled
      samples within cow and sampling day, whereas active ghrelin was measured in
      samples obtained 30 min before and after feeding at 0800 h. Postpartum, dry
      matter intake increased at a lower rate with infusion compared with the control.
      Arterial, portal venous, and hepatic venous plasma concentrations of the measured
      gut peptides were unaffected by abomasal glucose infusion. The arterial, portal
      venous, and hepatic venous plasma concentrations of glucose-dependent
      insulinotropic polypeptide and glucagon-like peptide 1(7-36) amide increased
      linearly from 12 d prepartum to 29 d postpartum. Plasma concentrations of
      oxyntomodulin were unaffected by day relative to parturition. Arterial and portal
      venous plasma concentrations of ghrelin were lower postfeeding compared with
      prefeeding concentrations. Arterial plasma concentrations of ghrelin were
      greatest prepartum and lowest at 4 d postpartum, giving a quadratic pattern of
      change over the transition period. Positive portal venous-arterial and hepatic
      venous-arterial concentration differences were observed for glucagon-like peptide
      1(7-36) amide. A negative portal venous-arterial concentration difference was
      observed for ghrelin pre-feeding. The remaining portal venous-arterial and
      hepatic venous-arterial concentration differences of gut peptides did not differ
      from zero. In conclusion, increased postruminal glucose supply to postpartum
      transition dairy cows reduced feed intake relative to control cows, but did not
      affect arterial, portal venous, or hepatic venous plasma concentrations of gut
      peptide hormones. Instead, gut peptide plasma concentrations increased as
      lactation progressed. Thus, the lower feed intake of postpartum dairy cows
      receiving abomasal glucose infusion was not attributable to changes in gut
      peptide concentrations.

PMID- 21094745
TI  - The effect of a national mastitis control program on the attitudes, knowledge,
      and behavior of farmers in the Netherlands.
AB  - Over the years, much effort has been put into implementing mastitis control
      programs in herds. To further improve utilization of such programs, there needs
      to be an understanding of the attitudes, knowledge, and behavior of farmers
      regarding udder health, and the way this can be influenced by mastitis control
      programs. This study aimed to explore the effect of a national mastitis control
      program on Dutch farmers' attitudes, knowledge, and behavior regarding mastitis.
      A total of 378 dairy farmers completed a survey on attitudes, knowledge, and
      behavior regarding mastitis before the start of a national mastitis control
      program in 2004, and 204 completed a similar survey in the final year of the
      program (2009). Although the average annual bulk milk somatic cell count (BMSCC)
      remained the same, the farmers' self-reported attitudes, knowledge, and behavior
      changed significantly. The problem level of BMSCC decreased from 285,000 cells/mL
      in 2004 to 271,000 cells/mL in 2009. More farmers perceived that they had
      sufficient knowledge about the prevention of mastitis (34% in 2004 vs. 53% in
      2009) and they more often perceived that they knew the cause of a mastitis
      problem (25% in 2004 vs. 37% in 2009). The use of gloves for milking increased
      from 15 to 46%, the use of a standardized mastitis treatment protocol increased
      from 7 to 34%, and freestalls were cleaned more often (2.28 vs. 2.51 times/d) in
      2009 compared with 2004. Most changes in attitudes, knowledge, and behavior did
      not differ between groups of dairy farmers whose herds had an initially low (<=
      162,000 cells/mL), medium (163,000 to 205,000 cells/mL), or high (>206,000
      cells/mL) BMSCC. The high BMSCC group significantly decreased their annual BMSCC
      level by 15,000 cells/mL. Regression analysis showed that the decrease in BMSCC
      was associated with a change in farmers' perceptions (e.g., increased perceived
      knowledge about the effect of the milking machine on mastitis) and with a change
      in certain management practices (e.g., disinfecting all teats after milking). The
      results showed that a national mastitis control program affected the attitudes,
      knowledge, and behavior of farmers regarding mastitis and could contribute to
      udder health improvement in the long term.

PMID- 21094746
TI  - Stability in the rumen and effect on plasma status of single oral doses of
      vitamin D and vitamin E in high-yielding dairy cows.
AB  - The ruminal fate of the fat-soluble vitamins D and E was studied in dairy cows.
      Ten to 15 kg of ruminal contents was taken from each cow through a ruminal
      fistula. A sample was taken out (0-h sample) and the rest of the contents were
      mixed with 4,360 mg of all-rac-alpha-tocopheryl acetate (vitamin E; study 1) or
      4,360 mg of all-rac-alpha-tocopheryl acetate, 250 mg of ergocalciferol (vitamin
      D(2)), and 250 mg of cholecalciferol (vitamin D(3); study 2). After mixing, the
      ruminal contents were returned to the respective cows. Blood was collected 0, 6,
      24, and 30 h after introducing the vitamins into the rumen. Samples of ruminal
      contents were collected at 0, 1, 2, 4, 6, 24, and 30 h (in vivo). From the 1-h
      sample, 6 subsamples from each cow were incubated at 37  degrees C and taken out
      at 2, 4, 6, 12, 24, and 30 h (in vitro). In vivo concentrations of added alpha
      tocopherol, ergocalciferol, and cholecalciferol in the rumen first increased and
      subsequently declined due to dilution effects of eating and passage out of the
      rumen. The level of the free-alcohol form of alpha-tocopherol from the natural
      content in feed was constant throughout the in vivo study, in contrast to the
      content of total alpha-tocopherol, which indicated that no hydrolysis of the
      acetate form into alcohol form happened in the rumen. In vitro, all added
      vitamins were found at constant levels; hence, none of the added vitamins were
      degraded in ruminal contents. The concentration of alpha-tocopherol in plasma
      increased at a rate per milligram of ruminally introduced alpha-tocopherol below
      the rate of the increase in plasma ergocalciferol or cholecalciferol metabolites
      per milligram of introduced ergocalciferol or cholecalciferol, respectively, over
      24h. In conclusion, ergocalciferol, cholecalciferol, and alpha-tocopheryl acetate
      proved to be stable in the rumen and in ruminal contents from high-yielding dairy
      cows. Changes in plasma concentrations of the vitamins relative to the amount of
      vitamin introduced to the rumen indicated a lower effect on plasma status of
      ergocalciferol than of cholecalciferol, and an even lower effect of alpha
      tocopherol. The limited plasma response after a single dose of alpha-tocopheryl
      acetate led to the conclusion that oral single dose therapy with all-rac-alpha
      tocopheryl acetate is of limited physiological value.

PMID- 21094747
TI  - Correlated changes in behavioral indicators of lameness in dairy cows following
      hoof trimming.
AB  - Cow gait, walking speed, time spent lying down, and distribution of weight among
      legs when standing during the week before and up to 5 wk after hoof trimming were
      assessed in 48 lactating Holstein cows housed in freestall pens to examine how
      changes in gait score following hoof trimming were correlated with other
      behavioral changes. Gait responses to hoof trimming varied between cows, with the
      majority showing no change or an increase in gait score. Walking speed was
      reduced after hoof trimming, and this decrease was maintained during the
      following 4 wk. The change in walking speed following hoof trimming negatively
      correlated with the change in gait (r = -0.33). Before hoof trimming, lame cows
      showed a greater standard deviation of the weight applied to the rear legs (38.4
      vs. 27.2; standard error of the difference = 4.6). After hoof trimming, lame cows
      showed a quadratic increase in the standard deviation of the weight applied to
      the rear legs and the rear leg weight ratio, whereas no time trend existed for
      nonlame cows. The change in gait following hoof trimming was negatively
      correlated with the change in leg weight ratio (r = -0.44). Before hoof trimming,
      lame cows spent more time lying down each day than nonlame cows (801.7 vs. 731.7
      min/d; standard error of the difference = 29.7). Both lame and nonlame cows
      increased the time they spent each day lying down after hoof trimming, and daily
      lying time remained higher for up to 5 wk after hoof trimming. The change in time
      spent lying down after hoof trimming was correlated with the change in gait (r =
      0.30) and the change in leg weight ratio (r = -0.47). Using automated methods of
      lameness detection shows promise as a way of continuously monitoring animals to
      detect changes in behavior associated with the onset of or recovery from
      lameness.

PMID- 21094748
TI  - Risk factors for postpartum uterine diseases in dairy cows.
AB  - The objective of this observational study was to investigate the risk factors for
      metritis, purulent vaginal discharge, and cytological endometritis. The
      hypothesis was that purulent vaginal discharge and cytological endometritis would
      have different risk factors because they represent distinct manifestations of
      uterine disease. Data generated from 1,363 Holstein cows (3 herds) enrolled in a
      randomized clinical trial were used. Calving history, periparturient disease
      incidence, and body condition score at calving and at 63 d in milk (DIM) were
      recorded. Serum nonesterified fatty acid concentration was measured once during
      the week before expected calving. Serum nonesterified fatty acid, beta
      hydroxybutyric acid, and haptoglobin (Hapto) concentrations were measured at 4 +/
      3, 11 +/- 3, and 18 +/- 3 DIM. Serum progesterone concentration was measured at
      21 +/- 3, 35 +/- 3, 49 +/- 3, and 63 +/- 3 DIM. Metritis was diagnosed by farm
      managers within the first 20 DIM using a standardized definition. Cows were
      examined at 35 +/- 3 DIM by a veterinarian for purulent vaginal discharge
      (mucopurulent or worse vaginal discharge; Metricheck device) and cytological
      endometritis (>= 6% polymorphonuclear cells on endometrial cytology; cytobrush
      device). Statistical analyses were performed using multivariable logistic
      regression models for each disease, accounting for the random effect of herd.
      Risk factors for metritis included increased nonesterified fatty acid prepartum
      (>= 0.6 mmol/L), dystocia, retained placenta, and increased Hapto in the first
      week postpartum (>= 0.8 g/L). Risk factors for purulent vaginal discharge
      included twinning, dystocia, metritis, and increased Hapto (>= 0.8 g/L) in the
      first week postpartum. Risk factors for cytological endometritis included low
      body condition score at parturition (<= 2.75), hyperketonemia (>= 1,100 MUmol/L),
      and increased Hapto (>= 0.8 g/L) in the first week postpartum. These results
      support the hypothesis that some of the risk factors for purulent vaginal
      discharge and cytological endometritis are different, which supports that they
      are distinct manifestations of uterine disease.

PMID- 21094749
TI  - Time budgets of lactating dairy cattle in commercial freestall herds.
AB  - The aim of this study was to examine the time budgets of 205 lactating dairy cows
      housed in 16 freestall barns in Wisconsin and to determine the relationships
      between components of the time budget and herd- and cow-level fixed effects using
      mixed models. Using continuous video surveillance, time lying in the stall, time
      standing in the stall, time standing in the alleys (including drinking), time
      feeding, and time milking (time out of the pen for milking and transit) during a
      24-h period were measured for each cow. In addition, the number of lying bouts
      and the mean duration of each lying bout per 24-h period were determined. Time
      milking varied between cows from 0.5 to 6.0 h/d, with a mean +/- standard
      deviation of 2.7 +/- 1.1h/d. Time milking was influenced significantly by pen
      stocking density, and time milking negatively affected time feeding, time lying,
      and time in the alley, but not time standing in the stall. Locomotion score,
      either directly or through an interaction with stall base type (a rubber crumb
      filled mattress, MAT, or sand bedding, SAND), influenced pen activity. Lame cows
      spent less time feeding, less time in the alleys, and more time standing in the
      stalls in MAT herds, but not in SAND herds. The effect of lameness on lying time
      is complex and dependent on the time available for rest and differences in
      resting behavior observed between cows in MAT and SAND herds. In MAT herds, rest
      was characterized by a larger number of lying bouts of shorter duration than in
      SAND herds (mean = 14.4; confidence interval, CI: 12.4 to 16.5 vs. mean = 10.2;
      CI: 8.2 to 12.2 bouts per d, and mean = 1.0; CI: 0.9 to 1.1 vs. mean = 1.3, CI:
      1.2 to 1.4h bout duration for MAT and SAND herds, respectively). Lameness was
      associated with an increase in time standing in the stall and a reduction in the
      mean (CI) number of lying bouts per day from 13.2 (CI: 12.3 to 14.1) bouts/d for
      nonlame cows to 10.9 (CI: 9.30 to 12.8) bouts/d for moderately lame cows, and an
      overall reduction in lying time in MAT herds compared with SAND herds (11.5; CI:
      10.0 to 13.0 vs. 12.7; CI: 11.0 to 14.3h/d, respectively). These results show
      that time out of the pen milking, stall base type, and lameness significantly
      affect time budgets of cows housed in freestall facilities.

PMID- 21094750
TI  - Effectiveness of different footbath solutions in the treatment of digital
      dermatitis in dairy cows.
AB  - Three experiments were conducted to test the effectiveness of different footbath
      solutions and regimens in the treatment of digital dermatitis (DD) in dairy cows.
      During the study, groups of cows walked through allocated footbath solutions
      after milking on 4 consecutive occasions. All cows were scored weekly for DD
      lesion stage on the hind feet during milking. A "transition grade" was assigned
      on the basis of whether the DD lesions improved (1) or deteriorated or did not
      improve (0) from week to week. This grade per cow was averaged for all cows in
      the group. In experiment 1, 118 cows were allocated to 1 of 3 footbath treatments
      for 5 wk: (1) 5% CuSO(4) each week, (2) 2% ClO(-) each week, or (3) no footbath
      (control). The mean transition grade, and proportion of cows without DD lesions
      at the end of the trial were significantly higher for treatment 1 above (0.36,
      0.13, and 0.11, respectively; standard error of the difference, SED = 0.057). In
      experiment 2, 117 cows were allocated to 1 of 4 footbath treatment regimens for 8
      wk: (1) 5% CuSO(4) each week, (2) 2% CuSO(4) each week, (3) 5% CuSO(4) each
      fortnight, or (4) 2% CuSO(4) each fortnight. For welfare reasons, cows allocated
      to the weekly and fortnightly footbath regimens had an average prevalence of >60%
      and <=25% active DD at the start of the trial, respectively. Significantly more
      cows had no DD lesions (0.53 vs. 0.36, respectively; SED = 0.049), and the mean
      transition grade of DD lesions was higher in the 5% compared with the 2% weekly
      CuSO(4) treatment (0.52 vs. 0.38, respectively; SED = 0.066). Similarly,
      significantly more cows had no DD lesions in the 5% compared with the 2%
      fortnightly CuSO(4) treatments (0.64 vs. 0.47, respectively; SED = 0.049). In
      experiment 3, 95 cows were allocated to 1 of 3 footbath treatments: (1) each week
      alternating 5% CuSO(4) with 10% salt water, (2) each week alternating 5% CuSO(4)
      with water, or (3) 5% CuSO(4) each fortnight (control). After 10 wk, more cows
      had no DD in the salt water treatment than in the control treatment (0.35 vs.
      0.26, respectively; SED = 0.038), but levels of active lesions were higher for
      this treatment than in the other 2 treatments (0.17, 0.00, and 0.13,
      respectively; SED = 0.029). Treatment did not affect mean transition grade of DD
      lesions. In conclusion, CuSO(4) was the only footbath solution that was
      consistently effective for treatment of DD. In cases when DD prevalence was high,
      a footbath each week using 5% CuSO(4) was the most effective treatment.

PMID- 21094751
TI  - Herd-level prevalence of Johne's disease in Utah and adjacent areas of the
      intermountain west as detected by a bulk-tank milk surveillance project.
AB  - The objectives of this study were to estimate the dairy herd-level prevalence of
      Johne's disease (JD) in Utah and nearby areas of the intermountain west and to
      estimate the sensitivity of a single bulk-tank milk test for JD detection. Two
      milk samples from all bulk tanks on the study farms were collected 1 mo apart.
      Samples were frozen and shipped to a laboratory for JD testing. An ELISA to
      measure total IgG antibody specific against Mycobacterium avium ssp.
      paratuberculosis, the etiological agent that causes JD, and a quantitative real
      time PCR to detect M. avium ssp. paratuberculosis DNA were used; both tests were
      designed for bulk milk. Of the dairy farms in the study area, 170/246 (69%)
      participated. Positive JD results were found in bulk milk from 67/170 (39%) of
      dairy farms in Utah and adjacent areas. There were 138 JD-positive bulk-tank
      results from 241 bulk-tank samples from the 67 positive herds. The sensitivity of
      the bulk milk testing for detection of JD was 138/241(57%). From the 103 JD
      negative farms, 235 bulk-tank samples tested negative for JD. The probability of
      false-negative results on a single bulk-milk sample was (1 - 0.57) = 0.43. For
      farms with 1 bulk tank, 2 samples collected 1 mo apart, with both samples testing
      negative (by both ELISA and quantitative real-time PCR) for JD, the true-negative
      probability was [1 - (0.43)(2)] = (1 - 0.18) = 82%. For farms with at least 2
      bulk tanks, at least 4 samples tested, with all results negative for JD, the true
      negative probability was at least 97%. Results support other estimates that
      prevalence of JD has increased over the last 15 to 20 yr. However, the prevalence
      detected was 3 times that from a recent report where 13% of dairy herds in the
      western US were positive. The increase in JD suggests that current control
      programs, at least as applied, are not effective. Bulk milk testing is a
      practical way to screen dairy herds for presence of JD. Studies are needed
      regarding the use of individual cow milk tests for accuracy, practicality, and
      effectiveness in reducing the prevalence of JD in dairy herds.

PMID- 21094752
TI  - Effect of interval between induction of ovulation and artificial insemination
      (AI) and supplemental progesterone for resynchronization on fertility of dairy
      cows subjected to a 5-d timed AI program.
AB  - Objectives were to investigate 2 intervals from induction of ovulation to
      artificial insemination (AI) and the effect of supplemental progesterone for
      resynchronization on fertility of lactating dairy cows subjected to a 5-d timed
      AI program. In experiment 1, 1,227 Holstein cows had their estrous cycles
      presynchronized with 2 injections of PGF(2alpha) at 46 and 60 d in milk (DIM).
      The timed AI protocols were initiated with GnRH at 72 DIM, followed by 2
      injections of PGF(2alpha) at 77 and 78 DIM and a second injection of GnRH at
      either 56 (OVS56) or 72h (COS72) after the first PGF(2alpha) of the timed AI
      protocols. All cows were time-inseminated at 72h after the first PGF(2alpha)
      injection. Pregnancy was diagnosed on d 32 and 60 after AI. In experiment 2, 675
      nonpregnant Holstein cows had their estrous cycles resynchronized starting at 34
      d after the first AI. Cows received the OVS56 with (RCIDR) or without (RCON)
      supplemental progesterone, as an intravaginal insert, from the first GnRH to the
      first PGF(2alpha). Pregnancy diagnoses were performed on d 32 and 60 after AI.
      During experiment 2, subsets of cows had their ovaries scanned by ultrasonography
      at the first GnRH, the first PGF(2alpha), and second GnRH injections of the
      protocol. Blood was sampled on the day of AI and 7 d later, and concentrations of
      progesterone were determined in plasma. Cows were considered to have a
      synchronized ovulation if they had progesterone <1 and >2.26 ng/mL on the day of
      AI and 7 d later, respectively, and if no ovulation was detected between the
      first PGF(2alpha) and second GnRH injections during resynchronization. In
      experiment 1, the proportion of cows detected in estrus at AI was greater for
      COS72 than OVS56 (40.6 vs. 32.4%). Pregnancy per AI (P/AI) did not differ between
      OVS56 (46.4%) and COS72 (45.5%). In experiment 2, cows supplemented with
      progesterone had greater P/AI compared with unsupplemented cows (51.3 vs. 43.1%).
      Premature ovulation tended to be greater for RCON than RCIDR cows (7.5 vs. 3.6%),
      although synchronization of the estrous cycle after timed AI was similar between
      treatments. Timing of induction of ovulation with GnRH relative to insemination
      did not affect P/AI of dairy cows enrolled in a 5-d timed AI program.
      Furthermore, during resynchronization starting on d 34 after the first AI,
      supplementation with progesterone improved P/AI in cows subjected to the 5-d
      timed AI protocol.

PMID- 21094753
TI  - The effect of subclinical mastitis on milk yield in dairy goats.
AB  - The aims of this study were to estimate milk yield (MY) losses associated with
      subclinical intramammary infection (IMI) in dairy goats and to assess if somatic
      cell count (SCC) can be used to estimate such MY losses. We used 2 data sets to
      study these questions. The first data set consisted of 5 herds. Milk production
      and SCC were recorded during 1 lactation. From approximately 100 does in each
      herd, milk samples were collected on 3 occasions during lactation for
      bacteriological culture. Linear mixed regression was used to estimate the effect
      of IMI on MY. The second data set consisted of 6 large herds, in which some of
      the goats had an extended lactation (>=2 yr). Milk yield and SCC data were
      recorded without bacteriological culture. The data showed that bacterial
      infection was related to an increase in SCC. Infections with major pathogens were
      rare and associated with a decreased MY; infection with coagulase-negative
      staphylococci did not affect MY, whereas infection with Corynebacterium bovis was
      associated with increased MY. A negative correlation was observed between SCC and
      MY, but the data suggested that this negative correlation was attenuated rather
      than caused by IMI. Furthermore, SCC seemed to be affected by MY via a dilution
      effect. Hypotheses about biological mechanisms behind these observations are
      discussed. This paper shows that MY losses caused by subclinical udder infections
      are limited in goats, and that SCC cannot be used to estimate the magnitude of
      these losses.

PMID- 21094754
TI  - Molecular and epidemiological characterization of bovine intrauterine Escherichia
      coli.
AB  - Escherichia coli are believed to be associated with postpartum metritis and
      endometritis but their role in the pathogenesis of both diseases is still
      undefined. In this study, uterine swabs for E. coli isolation were collected from
      374 lactating Holstein cows housed on 4 commercial farms near Ithaca, New York. A
      total, 125 of 374 cows (33.4%) were positive for E. coli culture. Standard
      multiplex PCR protocols were used to screen the isolates for the presence of 32
      virulence factor genes. Cows that had twin parturition were 4.4 times more likely
      to have intrauterine E. coli contamination than those that gave birth to single
      live female calves. Stillborn parturition and birth of single live male calves
      also increased the odds of intrauterine contamination by E. coli (3.7- and 1.6
      fold, respectively) compared with birth of live female calves. Six virulence
      factors, common to extraintestinal and enteroaggregative E. coli, were found to
      be associated with metritis and endometritis: fimH, hlyA, cdt, kpsMII, ibeA, and
      astA. The virulence factor gene fimH was the most prevalent and the most
      significant: intrauterine E. coli carrying fimH and at least 1 of the other 5
      identified virulence factors were pathogenic, and phylogenetic analysis based on
      the nucleotide sequence of DNA gyrase from 41 such IUEC revealed 2 clades.

PMID- 21094755
TI  - Short communication: Identification of the bovine sterol regulatory element
      binding protein-1c promoter and its activation by liver X receptor.
AB  - Sterol regulatory element binding proteins (SREBP) are a family of transcription
      factors that regulate cholesterogenesis and lipogenesis. Sterol regulatory
      element binding proteins-1a and -1c are transcribed from the same gene by the use
      of alternate promoters, and only differ at their first exon. Sterol regulatory
      element binding protein-1c is hypothesized to be an important regulator of genes
      involved in milk fat synthesis in the lactating dairy cow. However, the bovine
      SREBP-1c promoter has not been previously characterized, and studies to date that
      have investigated the role of SREBP-1 in the bovine mammary gland have not
      distinguished between isoforms 1a and 1c. The purpose of this study was to
      characterize the bovine SREBP-1c promoter and to investigate the DNA elements
      involved in the regulation of SREBP-1c expression by the liver X receptor agonist
      T0901317 in 2 different bovine mammary epithelial cell lines. Luciferase reporter
      constructs containing the wild-type SREBP-1c promoter or constructs with mutated
      liver X receptor response elements or sterol response element were transfected
      into MacT cells and bovine mammary epithelial (BME-UV) cells. We have
      demonstrated that the liver X receptor response elements sites in the SREBP-1c
      promoter are necessary for mediating the T0901317 response, and that stimulation
      through the sterol response element site plays only a minor role in this pathway.
      This report describes the bovine SREBP-1c promoter and its regulation by liver X
      receptor in bovine mammary epithelial cells.

PMID- 21094756
TI  - Technical note: An apparatus for catheterization of the lateral brain ventricle
      in Holstein cows.
AB  - A stereotaxic apparatus for access to the lateral brain ventricle of Holstein
      cows was constructed. This apparatus permits topographic orientation on the head
      of an anesthetized cow that has been placed in right lateral recumbency. After
      assessing the XY-plane in parallel to the frontal bone, correct coordinates in
      reference to the skullcap were adjusted. The lateral brain ventricles were
      accessed by drilling holes perpendicular to the XY-plane. The subsequent surgical
      implant of a tailor-made cannula guide enabled the repeatable placement of a
      catheter. This permanent catheter allowed the frequent withdrawal of
      cerebrospinal fluid from and injections into cerebral ventricles of
      nonanesthetized dairy cows. This method is critical for elucidating the role of
      central hormones, metabolites, and electrolytes in the regulation of diverse
      physiological processes and for the study of neuropathological disorders in cows.

PMID- 21094757
TI  - Dietary sodium butyrate supplementation increases digestibility and pancreatic
      secretion in young milk-fed calves.
AB  - The aim of this study was to test, in 8 calves fed milk formula based on soybean
      protein, the ability of sodium butyrate (SB) supplementation to improve nutrient
      digestibility and daily pancreatic secretions and to modify the kinetics of these
      secretions. Additionally, effects of duodenal SB infusion were evaluated. Plasma
      levels of gastrin, secretin, and cholecystokinin were measured. Butyrate
      supplementation in milk formula increased nutrient digestibility and total daily
      pancreatic secretions. For juice volume, this increase was most important from 12
      to 17h after the morning meal. During the 3-h postprandial period, oral SB
      supplementation reduced the physiological decrease of postprandial pancreatic
      secretion (while duodenal digesta flow rate was maximal) and had a minor effect
      on plasma gut regulatory peptide concentrations. Compared with the diet without
      SB, ingestion of SB stimulated pancreatic secretion. Taken together, these
      results could explain the measured increase in nutrient digestibility. The data
      obtained after duodenal SB infusion did not indicate an effect on pancreatic
      secretion, apart from elevated lipase output compared with control. The
      mechanisms responsible for these events are not known and circulating gut
      regulatory peptides do not seem to be implicated. Our work brings new results
      regarding SB as a feed additive in young calf nutrition.

PMID- 21094758
TI  - Effects of Bacillus subtilis natto on performance and immune function of
      preweaning calves.
AB  - The effects of Bacillus subtilis natto on performance and immune function of
      dairy calves during the preweaning phase were investigated in this study. Twelve
      Holstein male calves 7 +/- 1 d of age were randomly allotted to 2 treatments of 6
      calves. The Bacillus subtilis natto was mixed with milk and fed directly to the
      calves. The calves were weaned when their starter intake reached 2% of their
      weight. Blood was collected and IgA, IgE, IgG, IgM, and cytokine levels in the
      serum of all the calves were determined. The results showed that Bacillus
      subtilis natto increased general performance by improving the average daily gain
      and feed efficiency and advanced the weaning age of the calves. No difference was
      observed in serum IgE, IgA, and IgM, whereas serum IgG was higher in the Bacillus
      subtilis natto-supplemented calves than in the control calves. Furthermore,
      calves fed with Bacillus subtilis natto were found to secrete more IFN-gamma, but
      tended to produce less IL-4 than did the control calves, although serum IL-6 and
      IL-10 were not affected. This study demonstrated that Bacillus subtilis natto did
      not stimulate IgE-mediated allergic reactions, but increased serum IgG and IFN
      gamma levels in the probiotic-fed calves. We propose that the viable probiotic
      characteristics of Bacillus subtilis natto benefit calf immune function.

PMID- 21094759
TI  - Nitrate and sulfate: Effective alternative hydrogen sinks for mitigation of
      ruminal methane production in sheep.
AB  - Twenty male crossbred Texel lambs were used in a 2 * 2 factorial design
      experiment to assess the effect of dietary addition of nitrate (2.6% of dry
      matter) and sulfate (2.6% of dry matter) on enteric methane emissions, rumen
      volatile fatty acid concentrations, rumen microbial composition, and the
      occurrence of methemoglobinemia. Lambs were gradually introduced to nitrate and
      sulfate in a corn silage-based diet over a period of 4 wk, and methane production
      was subsequently determined in respiration chambers. Diets were given at 95% of
      the lowest ad libitum intake observed within one block in the week before methane
      yield was measured to ensure equal feed intake of animals between treatments. All
      diets were formulated to be isonitrogenous. Methane production decreased with
      both supplements (nitrate: -32%, sulfate: -16%, and nitrate+sulfate: -47%
      relative to control). The decrease in methane production due to nitrate feeding
      was most pronounced in the period immediately after feeding, whereas the decrease
      in methane yield due to sulfate feeding was observed during the entire day.
      Methane-suppressing effects of nitrate and sulfate were independent and additive.
      The highest methemoglobin value observed in the blood of the nitrate-fed animals
      was 7% of hemoglobin. When nitrate was fed in combination with sulfate,
      methemoglobin remained below the detection limit of 2% of hemoglobin. Dietary
      nitrate decreased heat production (-7%), whereas supplementation with sulfate
      increased heat production (+3%). Feeding nitrate or sulfate had no effects on
      volatile fatty acid concentrations in rumen fluid samples taken 24h after
      feeding, except for the molar proportion of branched-chain volatile fatty acids,
      which was higher when sulfate was fed and lower when nitrate was fed, but not
      different when both products were included in the diet. The total number of rumen
      bacteria increased as a result of sulfate inclusion in the diet. The number of
      methanogens was reduced when nitrate was fed. Enhanced levels of sulfate in the
      diet increased the number of sulfate-reducing bacteria. The number of protozoa
      was not affected by nitrate or sulfate addition. Supplementation of a diet with
      nitrate and sulfate is an effective means for mitigating enteric methane
      emissions from sheep.

PMID- 21094761
TI  - Effects of increased supplementation of n-3 fatty acids to transition dairy cows
      on performance and fatty acid profile in plasma, adipose tissue, and milk fat.
AB  - The objective of this study was to determine the effects of feeding an increased
      amount of extruded flaxseed with high proportions of n-3 fatty acids (FA) to
      transition dairy cows on performance, energy balance, and FA composition in
      plasma, adipose tissue, and milk fat. Multiparous Israeli-Holstein dry cows (n =
      44) at 256 d of pregnancy were assigned to 2 treatments: (1) control cows were
      fed prepartum a dry-cow diet and postpartum a lactating-cow diet that consisted
      of 5.8% ether extracts; and (2) extruded flaxseed (EF) cows were supplemented
      prepartum with 1 kg of extruded flaxseed (7.9% dry matter)/cow per d, and
      postpartum were fed a diet containing 9.2% of the same supplement. The EF
      supplement was fed until 100 d in milk. On average, each pre- and postpartum EF
      cow consumed 160.9 and 376.2g of C18:3n-3/d, respectively. Postpartum dry matter
      intake was 3.8% higher in the EF cows. Milk production was 6.4% higher and fat
      content was 0.4% U lower in the EF group than in the controls, with no
      differences in fat and protein yields. Energy balance in the EF cows was more
      positive than in the controls; however, no differences were observed in
      concentrations of nonesterified fatty acids and glucose in plasma. Compared with
      controls, EF cows had greater proportions of C18:3n-3 in plasma and adipose
      tissue. The proportion of n-3 FA in milk fat was 3.7-fold higher in the EF cows,
      and the n-6:n-3 ratio was decreased from 8.3 in controls to 2.3 in the EF cows.
      Within-group tests revealed that the C18:3n-3 content in milk fat in the EF cows
      was negatively correlated with milk fat percentage (r = -0.91) and yield (r = 
      0.89). However, no decrease in de novo synthesis of less than 16-carbon FA was
      found in the EF group, whereas C16:0 yields were markedly decreased. It appears
      that the enrichment of C18:3n-3 in milk fat was limited to approximately 2%, and
      the potential for increasing this n-3 FA in milk is higher for cows with lower
      milk fat contents. In conclusion, feeding increased amounts of C18:3n-3 during
      the transition period enhanced dry matter intake postpartum, increased milk
      production, decreased milk fat content, and improved energy balance. Increased
      amounts of EF considerably influenced the FA profile of plasma, adipose tissue,
      and milk fat. However, the extent of C18:3n-3 enrichment in milk fat was limited
      and was negatively correlated with milk fat content and yield.

PMID- 21094760
TI  - Milk performance and glucose metabolism in dairy cows fed rumen-protected fat
      during mid lactation.
AB  - Feeding rumen-protected fat (RPF) can improve energy supply for dairy cows but it
      affects glucose metabolism. Glucose availability is a precondition for high milk
      production in dairy cows. Therefore, this study investigated endocrine regulation
      of glucose homeostasis and hepatic gene expression related to glucose production
      because of RPF feeding in lactating cows. Eighteen Holstein dairy cows during
      second lactation were fed either a diet containing RPF (mainly C16:0 and C18:1;
      FD; n = 9) or a control diet based on corn starch (SD; n = 9) for 4 wk starting
      at 98 d in milk (DIM). Feed intake and milk yield were measured daily and milk
      composition once a week. Blood samples were taken weekly for analyses of plasma
      triglyceride, nonesterified fatty acids (NEFA), beta-hydroxybutyrate, bilirubin,
      urea, lactate, glucose, insulin, and glucagon. At 124 DIM, an intravenous glucose
      tolerance test (GTT; 1g/kg of BW(0.75)) was performed after a 12-h period without
      food. Blood samples were taken before and 7, 14, 21, and 28 min after glucose
      administration, and plasma concentrations of glucose, insulin, and glucagon were
      measured. Glucose half-life as well as areas under the concentration curve for
      glucose, insulin, and glucagon were calculated. After slaughter at d 28 of
      treatment, liver samples were taken to measure mRNA abundance of pyruvate
      carboxylase, cytosolic phosphoenolpyruvate carboxykinase, glucose 6-phosphatase
      (G6Pase), and facilitative glucose transporter 2. Dry matter intake, but not
      energy and protein intake, was lower in FD than in SD. Milk yield during
      lactation decreased more in SD than in FD, and milk protein was lower in FD than
      in SD. Plasma concentrations of triglycerides and NEFA were higher in FD than in
      SD. Plasma insulin concentrations were lower and the glucagon:insulin ratios were
      higher in FD than in SD. Fasting glucose concentration before GTT was lower, and
      fasting glucagon concentrations tended to be higher in FD than in SD. In liver,
      fat content tended to be higher and G6Pase mRNA abundance was lower in FD than in
      SD. Lower hepatic G6Pase mRNA abundance was associated with reduced fasting
      plasma glucose concentrations, but the glucose-induced insulin response was not
      affected by RPF feeding. Hepatic G6Pase gene expression might be affected by DMI
      and might be involved in the regulation of glucose homeostasis in dairy cows,
      resulting in a lower hepatic glucose output after RPF feeding.

PMID- 21094762
TI  - A meta-analysis of passage rate estimated by rumen evacuation with cattle and
      evaluation of passage rate prediction models.
AB  - A meta-analysis of studies using the flux/compartmental pool method with
      indigestible neutral detergent fiber (iNDF) as internal marker was conducted to
      study the effect of extrinsic characteristics and forage type on particle passage
      rate (k(p)) in cattle. Further, the k(p) prediction equations in the National
      Research Council (NRC) and the Cornell Net Carbohydrate and Protein System
      (CNCPS) were evaluated. Data comprised 172 treatment means from 49 studies
      conducted in Europe and the United States. In total, 145 diets were fed to dairy
      cows and 27 to growing cattle. A prerequisite for inclusion of an experiment was
      that dry matter intake, neutral detergent fiber (NDF), proportion of concentrate
      in the diet, body weight, and diet chemical composition were determined or could
      be estimated. Mixed model regression analysis including a random study effect was
      used to generate prediction equations of k(p) and to investigate the
      relationships between NRC and CNCPS predictions and observed k(p) of iNDF.
      Prediction equations were evaluated by regressing residual values on the
      predicted values. The best-fit model when forage type was not included was k(p)
      (%/h) = 1.19+0.0879 * NDF intake (g/kg of body weight)+0.792 * proportion of
      concentrate NDF of total NDF+1.21 * diet iNDF:NDF ratio (adjusted residual mean
      square error = 0.23%/h). The best general equation accounting for an effect of
      forage type was as follows: k(p) (%/h) = F+1.54+0.0866 * NDF intake (g/kg of body
      weight) (adjusted residual mean square error = 0.21%/h), where F is the forage
      adjustment factor of the intercept. The value of F for grass silage, fresh grass,
      mixes of alfalfa and corn silage, and dry or ensiled alfalfa as sole forage
      component were 0.00, -0.91, +0.83, and +0.24, respectively. Relationships between
      predicted and observed k(p) were y = 0.53(+/- 0.187)+0.41( +/- 0.0373) *
      predicted k(p) and y = 0.58(+/- 0.162)+0.46(+/- 0.0377) * predicted k(p) for the
      NRC and CNCPS models, respectively. Residual analysis of the NRC and CNCPS models
      resulted in both significant mean biases (observed--predicted) of -2.40 and 
      1.70% and linear biases of -0.59 and -0.53, respectively. The results from this
      meta-analysis suggest that ruminal particulate matter k(p) is affected by forage
      type in the diet. Further, the evaluation of NRC and CNCPS models showed that
      passage rate equations developed from marker excretion curves markedly deviated
      from observed k(p) of iNDF derived using the rumen evacuation technique.

PMID- 21094763
TI  - Host specificity of the ruminal bacterial community in the dairy cow following
      near-total exchange of ruminal contents.
AB  - The purpose of this study was to examine the stability and host specificity of a
      cow's ruminal bacterial community following massive challenge with ruminal
      microflora from another cow. In each of 2 experiments, 1 pair of cows was
      selected on the basis of differences in ruminal bacterial community composition
      (BCC), determined by automated ribosomal intergenic spacer analysis (ARISA), a
      culture-independent "community fingerprinting" technique. Each pair of cows was
      then subjected to a 1-time exchange of >95% of ruminal contents without changing
      the composition of a corn silage/alfalfa haylage-based TMR. In experiment 1, the
      2 cows differed (P<0.01) in prefeed ruminal pH (mean = 6.88 vs. 6.14) and prefeed
      total VFA concentration (mean = 57 vs. 77 mM), averaged over 3 d. Following
      exchange of ruminal contents, ruminal pH and total VFA concentration in both cows
      returned to their preexchange values within 24h. Ruminal BCC also returned to
      near its original profile, but this change required 14 d for 1 cow and 61 d for
      the other cow. In experiment 2, the 2 other cows differed in prefeed ruminal pH
      (mean = 6.69 vs. 6.20) and total VFA concentration (mean = 101 vs. 136 mM).
      Following exchange of ruminal contents, the first cow returned to its preexchange
      pH and VFA values within 24h; the second cow's rumen rapidly stabilized to a
      higher prefeed pH (mean = 6.47) and lower prefeed VFA concentration (mean = 120
      mM) that was retained over the 62-d test period. Both cows reached somewhat
      different BCC than before the exchange. However, the BCC of both cows remained
      distinct and were ultimately more similar to that of the preexchange BCC than of
      the donor animal BCC. The data indicate that the host animal can quickly
      reestablish its characteristic ruminal pH and VFA concentration despite dramatic
      perturbation of its ruminal microbial community. The data also suggest that
      ruminal BCC displays substantial host specificity that can reestablish itself
      with varying success when challenged with a microbial community optimally adapted
      to ruminal conditions of a different host animal.

PMID- 21094764
TI  - Blood plasma concentrations of metabolic hormones and glucose during extended
      lactation in grazing cows or cows fed a total mixed ration.
AB  - An experiment was conducted to measure the effect of diet on circulating
      concentrations of metabolic hormones and metabolites in cows undergoing extended
      lactations. Two groups of 6 Holstein-Friesian cows managed for lactations of 670
      d were used in the experiment. One group was fully fed on a total mixed ration
      (TMR), whereas the other group grazed fresh pasture supplemented with grain
      (P+G). On 7 occasions between 332 and 612 d in milk, concentrations of metabolic
      hormones and glucose were measured in the blood plasma of each cow. Cows fed TMR
      gained more weight and body condition than P+G cows, but did not produce more
      milk during the study period. Only 3 of the TMR cows continued to lactate until
      612 d in milk compared with all 6 of the P+G cows. Blood plasma from cows fed TMR
      had higher concentrations of glucose, insulin, glucagon, insulin-like growth
      factor 1, and leptin, but lower concentrations of growth hormone, than that from
      P+G cows. These changes were consistent with the preferential deposition of
      energy into adipose tissue at the expense of milk production and presumably were
      induced by a diet that provided precursors for gluconeogenesis that were in
      excess of the requirements for maintenance and prevailing milk production. The
      mechanism responsible for some TMR cows putting on excess weight and reducing or
      ceasing milk production is uncertain, but this observation has important
      implications for the nutritional management of cows in extended lactation
      programs.

PMID- 21094765
TI  - Short communication: Effects of feeding pearl millet silage on milk production of
      lactating dairy cows.
AB  - Twenty Holstein cows were used in a randomized complete block experiment to
      determine the feeding value of pearl millet silage (MS) for dairy cows relative
      to corn silage (CS). Two isonitrogenous diets were formulated with a 53:47
      forage:concentrate ratio. Pearl millet silage and CS comprised 67% of the forages
      in each diet. Relative to CS, MS contained higher crude protein (13.0 vs. 9.4%),
      neutral detergent fiber (66.9 vs. 40.7%), and acid detergent fiber (38.8 vs.
      23.9%). Dietary treatments had no effect on dry matter (average = 23.9 kg/d) or
      crude protein (average = 4.2 kg/d) intake. However, cows fed MS consumed more
      neutral detergent fiber (9.7 vs. 8.3 kg/d) than did cows fed CS. Silage type had
      no effect on milk yield (average 38.0 kg/d), whereas energy-corrected milk (43.8
      vs. 38.6) and 4% fat-corrected milk (41.8 vs. 35.5 kg/d) were greater for cows
      fed MS than for those fed CS. Milk protein, lactose, and total solids
      concentrations were not influenced by dietary treatments. However, cows fed MS
      produced milk with a greater milk fat concentration (4.17 vs. 3.78%) than did
      cows fed CS. We concluded that MS, when compared with CS, had a similar effect on
      feed intake, milk yield, and milk efficiency. Because of increased milk fat
      concentration, cows fed MS produced more energy-corrected milk than did cows fed
      CS.

PMID- 21094766
TI  - Short communication: Detection of yeast DNA in omasal digesta of dairy cows
      consuming dried distillers grains and solubles.
AB  - Purine analysis is widely used to estimate microbial crude protein (MCP) flow,
      and the method assumes that all purines contained in feed are degraded in the
      rumen and that purines detected are of microbial origin. The objectives of our
      experiment were (1) to determine if DNA from yeast (Saccharomyces cerevisiae)
      contained in dried distillers grains and solubles (DDGS) escapes degradation in
      the rumen and (2) to estimate the proportion of yeast DNA compared with total
      bacterial DNA in omasal samples. Two ruminally fistulated Holstein dairy cows
      averaging 649 kg (SD = 42.0) and 126 d in milk (SD = 28.9) were fed in a
      crossover design during 2 periods of 21 d each. Treatments were (1) control, a
      total mixed ration (TMR) not containing DDGS and (2) a DDGS-based diet, a TMR in
      which DDGS were included at 30% of diet dry matter (DM). On d 20 and 21 at 0400
      and 1600 h, omasal digesta samples were collected via a ruminal cannula, and DNA
      was extracted from each sample in duplicate. The DNA samples were subjected to a
      real-time PCR assay to detect the presence of DNA from yeast. Forward and reverse
      primers and a probe were designed to target a DNA segment contained on the second
      chromosome of Saccharomyces cerevisiae. Real-time PCR amplification curves
      indicated the presence of yeast DNA in samples from both treatments.
      Specifically, the estimate of relative abundance of yeast DNA from digesta
      samples collected from animals consuming the diet containing DDGS was 9.46 +/-
      0.67/g of DM and was significantly higher than that from animals consuming no
      DDGS, which was observed to be 0.091 +/- 0.67/g of DM. Omasal samples were also
      analyzed for total bacterial DNA. Primers and a probe were designed from DNA
      encoding part of the 16S rRNA. When the DDGS-based diet was fed, the relative
      abundance of total bacterial DNA tended to increase from 610 to 626+/-3.82/g of
      DM. Results suggest that yeast DNA is detected in the omasum and this is
      increased when cows consume DDGS but it does not represent a significant
      proportion of total microbial DNA in the omasal digesta samples.

PMID- 21094767
TI  - Phenotypic and genetic characterization of novel somatic cell count traits from
      weekly or monthly observations.
AB  - The objectives of this study were (1) to explore traits that better capture
      weekly or monthly changes in somatic cell counts (SCC) than does the commonly
      used lactation-average SCC, (2) to estimate their heritabilities and
      relationships to clinical mastitis (CM), and (3) to determine if these traits are
      feasible for use in monthly testing schemes. Clinical mastitis and weekly test
      day (TD) records of SCC and milk production traits from 1,006 lactations of
      Swedish Red and Holstein cows collected from 1989 to 2004 were used (data set W).
      A data subset was also created to mimic monthly recording (data set M, 980
      lactations). Twenty SCC traits were defined, taking into account SCC general
      levels and variation along the lactation curve, time and level of infection, and
      time of recovery. To reduce dimensionality, cluster and stepwise logistic
      regression procedures were applied. In data set W, 3 traits, "standard deviation
      of SCC over the lactation," a discrete (0/1) indicator of "at least one TD with
      SCC >500,000 cells/mL", and "number of days sick in the widest SCC peak"
      (DWidest) were the variables kept both with cluster procedures and a stepwise
      logistic regression with the logit of CM as dependent variable. In data set M,
      DWidest was replaced by "number of SCC peaks" and "average number of days sick
      per peak" (ADSick). Lactation-average SCC (in the first 150 d or between 150 and
      305 d) did not enter into the logistic regression. Heritability estimates
      obtained for these new traits under a Bayesian setting and a Gibbs sampling
      approach were 10 to 16% (except for ADSick: 5%). Heritabilities were at least as
      high in the monthly data set as in the weekly data set. Thus, these SCC traits
      seem promising for use in breeding programs based on monthly milk recording.

PMID- 21094768
TI  - Predictive ability of subsets of single nucleotide polymorphisms with and without
      parent average in US Holsteins.
AB  - Genome-enabled prediction of breeding values using high-density panels (HDP) can
      be highly accurate, even for young sires. However, the cost of the assay may
      limit its use to elite animals only. Low-density panels (LDP) containing a subset
      of single nucleotide polymorphisms (SNP) may give reasonably accurate predictions
      and could be used cost-effectively with young males and females. This study
      evaluates strategies for selecting subsets of SNP for several traits, compares
      predictive ability of LDP with that of HDP, and assesses the benefits of
      including parent average (PA) as a predictor in models using LDP. Data consisting
      of progeny-test predicted transmitting ability (PTA) for net merit and 6 other
      traits of economic interest from 4,783 Holstein sires were evaluated using
      testing and training sets with regressions on their high-density genotypes and
      parent averages for net merit index. Additionally, SNP subsets of different sizes
      were selected using different strategies, including the "best" SNP based on the
      absolute values of their estimated effects from HDP models for either the trait
      itself or lifetime net merit, and evenly spaced (ES) SNP across the genome.
      Overall, HDP models had the best predictive ability, setting an upper bound for
      the predictive ability of LDP sets. Low-density panels targeting the SNP with
      strongest effects (for either a single trait or lifetime net merit) provided
      reasonably accurate predictions and generally outperformed predictions based on
      evenly spaced SNP. For example, evenly spaced sets would require at least 5,000
      to 7,500 SNP to reach 95% of the predictive ability provided by HDP. On the other
      hand, this level of predictive ability can be achieved with sets of 2,000 SNP
      when SNP are selected based on magnitude of estimated effects for the trait.
      Accuracy of predictions based on LDP can be improved markedly by including parent
      average as a fixed effect in the model; for example, a set with the 1,000 best
      SNP using the parent average achieved the 95% of the accuracy of a HDP model.

PMID- 21094769
TI  - SP110 as a novel susceptibility gene for Mycobacterium avium subspecies
      paratuberculosis infection in cattle.
AB  - The intracellular pathogen resistance 1 (Ipr1) gene has been reported to play a
      role in mediating innate immunity in a mouse model of Mycobacterium tuberculosis
      infection, and polymorphisms of its human ortholog, SP110 nuclear body protein,
      have been suggested to be associated with tuberculosis. Thus, the bovine SP110
      gene was considered to be a promising candidate for a genetic association study
      of bovine paratuberculosis, or Johne's disease, a chronic granulomatous enteritis
      caused by Mycobacterium avium ssp. paratuberculosis (MAP). Initially, single
      nucleotide polymorphisms (SNP) within the bovine SP110 gene were identified, and
      subsequently a population-based genetic association study was carried out.
      Seventeen new SNP along the SP110 gene were identified in Holstein-Friesian
      cattle, and 6 more were compiled from public databases. A total of 14 SNP were
      included in the association study of 2 independent populations. The SNP c.587A>G
      was found to be significantly associated with MAP infection, with the major
      allele A appearing to confer greater disease susceptibility in one of the
      analyzed populations. In addition, 2 haplotypes containing this SNP were also
      found to be associated with infection in the same population. The SNP c.587A>G is
      a nonsynonymous mutation that causes an amino acid change in codon 196 from
      asparagine to serine. In silico analyses point to SNP c.587A>G as a putative
      causal variant for susceptibility to MAP infection. The elucidation of the
      precise mechanism by which this SNP can exert its effect in the protein and, as a
      result, in the risk of infection, requires future functional analyses. Likewise,
      the absence of genetic association in one of the analyzed populations renders it
      necessary to carry out this study in other independent populations, with the aim
      of substantiating the repeatability of the present results. Nevertheless, the
      present results deepen our understanding of the genetic basis of susceptibility
      and resistance mechanisms related to MAP infection in cattle and, in turn,
      constitute a step forward toward the implementation of marker-assisted selection
      in breeding programs aimed at controlling paratuberculosis.

PMID- 21094770
TI  - Associations between novel single nucleotide polymorphisms in the Bos taurus
      growth hormone gene and performance traits in Holstein-Friesian dairy cattle.
AB  - Growth hormone, produced in the anterior pituitary gland, stimulates the release
      of insulin-like growth factor-I from the liver and is of critical importance in
      the control of nutrient utilization and partitioning for lactogenesis, fertility,
      growth, and development in cattle. The aim of this study was to discover novel
      polymorphisms in the bovine growth hormone gene (GH1) and to quantify their
      association with performance using estimates of genetic merit on 848 Holstein
      Friesian AI (artificial insemination) dairy sires. Associations with previously
      reported polymorphisms in the bovine GH1 gene were also undertaken. A total of 38
      novel single nucleotide polymorphisms (SNP) were identified across a panel of 22
      beef and dairy cattle by sequence analysis of the 5' promoter, intronic, exonic,
      and 3' regulatory regions, encompassing approximately 7 kb of the GH1 gene.
      Following multiple regression analysis on all SNP, associations were identified
      between 11 SNP (2 novel and 9 previously identified) and milk fat and protein
      yield, milk composition, somatic cell score, survival, body condition score, and
      body size. The G allele of a previously identified SNP in exon 5 at position 2141
      of the GH1 sequence, resulting in a nonsynonymous substitution, was associated
      with decreased milk protein yield. The C allele of a novel SNP, GH32, was
      associated with inferior carcass conformation. In addition, the T allele of a
      previously characterized SNP, GH35, was associated with decreased survival. Both
      GH24 (novel) and GH35 were independently associated with somatic cell count, and
      3 SNP, GH21, 2291, and GH35, were independently associated with body depth.
      Furthermore, 2 SNP, GH24 and GH63, were independently associated with carcass
      fat. Results of this study further demonstrate the multifaceted influences of GH1
      on milk production, fertility, and growth-related traits in cattle.

PMID- 21094771
TI  - Correlated selection responses for female fertility after selection for high
      protein yield or low mastitis frequency in Norwegian Red cows.
AB  - Correlated selection responses in female fertility were estimated from a
      selection experiment with 2 groups of Norwegian Red cows selected for high
      protein yield (HPY) and low mastitis frequency (LCM), respectively. Genetic
      trends were calculated for nonreturn rate within 56 d after first insemination
      (NR56) for heifers, first-lactation cows, and second- and third-lactation cows,
      calving interval between first and second calving (CIN), and interval from
      calving to first insemination (CFI) for first-lactation cows and for second- and
      third-lactation cows. A total of 5,001 cows from the selection experiment had
      estimated breeding values for fertility, of which 2,806 were HPY and 2,195 were
      LCM cows. Permutation tests showed significant genetic differences between LCM
      and HPY for all fertility traits except CFI for second- and third-lactation cows.
      Observed differences between mean EBV in HPY and in LCM were, with few
      exceptions, far outside the range of the permutation test (i.e., significantly
      different from zero). LCM cows were, in general, genetically more fertile than
      HPY cows, with higher NR56 in heifers and cows, shorter CIN, and shorter CFI in
      first lactation. Genetic differences between HPY and LCM after 6 cow-generations
      were 2.5 percentage units NR56 in heifers, 2 percentage units NR56 in cows, and 4
      d for CIN. No difference was found for CFI in second and third lactation. This is
      the first report of genetic change in female fertility as a correlated response
      after selection against mastitis.

PMID- 21094772
TI  - Application of a multiple-trait, multiple-country genetic evaluation model for
      female fertility traits.
AB  - The need to implement a method that can handle multiple traits per country in
      international genetic evaluations is evident. Today, many countries have
      implemented multiple-trait national genetic evaluations and they may expect to
      have their traits simultaneously analyzed in international genetic evaluations.
      Traits from the same country are residually correlated and the method currently
      in use, single-trait multiple across-country evaluation (ST-MACE), cannot handle
      nonzero residual correlations. Therefore, multiple-trait, multiple across-country
      evaluation (MT-MACE) was proposed to handle several traits from the same country
      simultaneously. To test the robustness of MT-MACE on real data, female fertility
      was chosen as a complex trait with low heritability. Data from 7 Holstein
      populations, 3 with 2 traits and 4 with 1 trait, were used. The differences in
      the estimated genetic correlations by MT-MACE and the single ST-MACE analysis
      (average absolute deviation of 0.064) were due to the bias of considering several
      traits from the same country in the ST-MACE analysis. However, the differences
      between the estimated genetic correlations by MT-MACE and multiple ST-MACE
      analyses avoiding more than one trait per country in each analysis (average
      absolute deviation of 0.066) were due to the lack of analysis of the correlated
      traits from the same country together and using the reported within-country
      genetic correlations. Applying MT-MACE resulted in reliability gain in
      international genetic evaluations, which was different from trait to trait and
      from bull to bull. The average reliability gain by MT-MACE over ST-MACE was 3.0
      points for domestic bulls and 6.3 points for foreign bulls. Even countries with 1
      trait benefited from the joint analysis of traits from the 2-trait countries.
      Another superiority of MT-MACE over ST-MACE is that the bulls that do not have
      national genetic evaluation for some traits from multiple trait countries will
      receive international genetic evaluations for those traits. Rank correlations
      were high between ST-MACE and MT-MACE when considering all bulls. However, the
      situation was different for the top 100 bulls. Simultaneous analysis of traits
      from the same country affected bull ranks, especially for top 100 bulls. Multi
      trait MACE is a recommendable and robust method for international genetic
      evaluations and is appropriate for handling multiple traits per country, which
      can increase the reliability of international genetic evaluations.

PMID- 21094773
TI  - Genetic analysis of clinical mastitis and somatic cell count traits in Austrian
      Fleckvieh cows.
AB  - The objectives of this study were to investigate genetic associations between
      clinical mastitis (CM) and different somatic cell count traits, and to examine
      their relationships, in terms of estimated breeding values, with other traits
      that are routinely evaluated in Austrian Fleckvieh dual-purpose cows. Records on
      veterinary treatments of CM were available from the Austrian health-monitoring
      project. For CM, 3 intervals in early lactation were considered: -10 to 50 d, 51
      to 150 d, and -10 to 150 d after calving. Within each interval, absence or
      presence of CM was scored as 1 or 0 based on whether or not the cow had recorded
      at least one veterinary treatment of CM. The average somatic cell score of the
      first 2 test-days after calving was defined as early lactation average somatic
      cell score, and lactation mean somatic cell score was the average of all test-day
      somatic cell scores from 8 to 305 d after calving. Subclinical mastitis was
      expressed as a binary trait based on prolonged elevated somatic cell counts. If
      somatic cell counts on 3 consecutive test-days in the interval from 8 to 305 d
      after calving were above 200,000 cells/mL, the binary variable subclinical
      mastitis was defined as 1 and otherwise 0. Records of Austrian Fleckvieh cows,
      with calving from January 1, 2007, to February 28, 2009, were analyzed using
      univariate and bivariate sire models. Threshold liability models were applied for
      binary traits, and Gaussian models were used for early lactation average somatic
      cell score and lactation mean somatic cell score. A Bayesian approach using Gibbs
      sampling was applied for genetic analyses. Posterior means of heritability of
      liability to CM were 0.06 and 0.02 in the first and second interval,
      respectively, and 0.05 in the full period (-10 to 150 d). Heritability estimates
      of somatic cell count traits were higher (0.09 to 0.13). The posterior mean of
      the genetic correlation between CM in lactation period 1 (-10 to 50 d after
      calving) and 2 (51 to 150 d after calving) was close to unity. Posterior means of
      genetic correlations between CM and somatic cell count traits ranged from 0.64 to
      0.77. Because CM and somatic cell count describe different aspects of udder
      health, information on both traits should be considered for selection of bulls.
      Correlations of sire breeding values revealed that especially the udder
      conformation trait udder depth may be useful as additional information to reduce
      both CM and somatic cell count.

PMID- 21094774
TI  - Technical note: A simplified PCR-based assay for the characterization of two
      prolactin variants that affect milk traits in sheep breeds.
AB  - In the present study, a rapid and cost-effective PCR-based assay was developed
      for the genetic identification of 2 different variants within intron 2 of the
      prolactin gene. This polymorphism has previously been associated with milk traits
      in some ovine breeds and was recently proposed as a potential marker for future
      breeding schemes in dairy sheep. Until now, 2 alleles (A and B) have been
      identified by PCR-RFLP that included HaeIII digestion of a 2.5-kb PCR fragment.
      By partial sequencing of the prolactin gene intron 2, it was found that the B
      variant results from a 23-bp deletion of the A variant of the prolactin gene and
      not from an extra HaeIII digestion site, as had been reported. This finding
      assisted the design of new primers for analysis of prolactin intron 2 variants
      based on the size of an easily amplified short PCR product, thereby avoiding the
      need and cost for additional digestions. The method was validated by genotyping
      80 animals from 2 breeds and showed 100% sensitivity and specificity compared
      with the PCR-RFLP assay. The established simplified PCR assay was then
      successfully used to genotype 356 Chios sheep.

PMID- 21094775
TI  - Effect of preservatives on the accuracy of mid-infrared milk component testing.
AB  - Our objective was to determine the effect of commonly used milk preservatives on
      the accuracy of fat, protein, and lactose content determination in milk by mid
      infrared (mid-IR) milk analysis. Two producer raw milks (Holstein and Jersey) and
      2 pasteurized modified milks, 1 similar to Holstein milk and 1 similar to Jersey
      milk were used as the 4 different milk sources. Seven different milk preservative
      approaches (K(2)Cr(2)O(7) and 6 different bronopol-based preservatives) and a
      portion of unpreserved milk for each of the 4 different milks sources were tested
      for fat B, lactose, protein, and fat A. The experiment was replicated 3 times (28
      d each) for a total of 84 d. Two mid-infrared (mid-IR) transmittance milk
      analyzers (an optical and a virtual filter instrument) were used. A large batch
      of pilot milk was prepared from pasteurized, homogenized, unpreserved whole milk,
      split into vials, quick frozen by immersion in liquid nitrogen, and transferred
      into a -80  degrees C freezer. Pilots were thawed and analyzed on each testing
      day during the study. Significant increases were observed in all uncorrected
      readings on the pilot milks over the 84 d of the study, but the increases were
      gradual and small on each instrument for all components. Results from the study
      were corrected for these changes. A significant difference in mid-IR fat A
      readings was observed, whereas no differences were detected for fat B, lactose,
      or protein between unpreserved and preserved milks containing 0.02%
      K(2)Cr(2)O(7.) Therefore, K(2)Cr(2)O(7) has little or no effect on mid-IR test
      results. All bronopol-based preservative approaches in this study differed in mid
      IR test results compared with K(2)Cr(2)O(7)-preserved and unpreserved milks, with
      the largest effect on protein results. Mid-IR uncorrected readings increased with
      time of refrigerated storage at 4 degrees C for all preservative approaches, with
      the largest increase for protein. The rate of increase in uncorrected readings
      with time of storage was always higher for raw milks than for pasteurized milks,
      and the stability of instrument zero was lower for raw milks than for pasteurized
      milks. The largest economic effect of a systematic bias caused by a preservative
      occurs when the milks used for calibration and routine testing for payment do not
      contain the same preservative or when calibration milks are preserved and milks
      for routine testing are unpreserved. These effects can create errors in payment
      for large dairy processing plants ranging from several hundred thousand to over a
      million dollars annually.

PMID- 21094776
TI  - Adoption of technology, management practices, and production systems in US milk
      production.
AB  - The introduction of new technology, management practices, and alternative
      production systems has resulted in rapid structural change in the US dairy
      industry. This paper examines adoption rates and adopter characteristics for the
      following dairy technologies, practices, and systems: holding pen with an udder
      washer, milking units with automatic take-offs, genetic selection technologies,
      recombinant bovine somatotropin, membership in the Dairy Herd Improvement
      Association, computerized feed delivery systems, computerized milking systems,
      use of a nutritionist to design feed rations, grazing, milking cows 3 times
      daily, and milking parlors. Four of these were used on a greater percentage of
      farms in 2005 than in 2000, but increased farm sizes and the interaction of farm
      size with adoption suggest a greater percentage of milk being produced under
      each, with the exception of grazing. Except for grazing, technologies were
      generally complementary.

PMID- 21094778
TI  - Immunologic aspects and rejection in solid organ versus reconstructive
      transplantation.
AB  - The immunosuppressive medications developed over the past 3 decades have paved
      the way for solid organ transplantation to become the treatment of choice for end
      stage organ failure. At the end of the century, composite tissue transplantation
      in humans was performed with success using the same immunosuppressive medications
      and therapeutic principles. A decade later, experience from >100 cases of
      reconstructive transplantation have increased the knowledge, changed the view,
      and affected the therapeutic principles in this novel field. We herein portray
      the evolution of this novel type of transplant with particular reference to
      immunologic aspects, particularly differences between reconstructive and solid
      organ transplantation.

PMID- 21094779
TI  - Chagas' disease and solid organ transplantation.
AB  - This review summarizes relevant published data on transplant recipients with
      Chagas' disease and of naive recipients transplanted with organs from infected
      donors. Unpublished experience from some of the largest transplant centers in
      Argentina is also included. The review outlines the guidelines for pretransplant
      evaluation and for posttransplant management formulated by the Chagas Disease
      Argentine Collaborative Transplant Consortium.

PMID- 21094780
TI  - Knowledge, attitudes, and behaviors of officials of religion about organ donation
      in Kahramanmaras, an eastern Mediterranean city of Turkey.
AB  - OBJECTIVE: To establish the knowledge, attitudes, and behaviors of the officials
      of religion, a group with potentially powerful influence on the society, in
      particular regarding organ donation. METHODS: This study, performed in
      Kahramanmaras Province, Turkey, included 416 of 641 officials of religion
      (64.9%): 295 of 492 imams (59.9%) and 121 of 149 Koran course educators (81.2%).
      RESULTS: The mean (SD) age of the study group was 37.2 (8.2) years. Only 1.4% had
      stated that carried organ donation cards. Of participants who had not donated
      organs asked whether they thought of donation, 14.1% answered yes, 17.1% answered
      no, and 68.8% were undecided. Of the study group, 88.2% considered organ donation
      appropriate according to their religion. The imams compared with Koran course
      educators, and men compared with women demonstrated higher rates of considering
      organ donation appropriate according to their religion (P < .05). Among
      participants who stated they had knowledge about organ donation, the 3 leading
      information sources were television, newspapers or journals, and in-service
      training by the Directorate of Religious Affairs. The 3 primary organs the study
      group stated they were aware of being transplanted were kidneys, liver, and
      heart. CONCLUSION: Although 88.2% of religious officials in the present study
      stated that organ donation was appropriate according to their religion, only 1.4%
      agreed to donate organs. Officials of religion hold an important place in
      society, and should be well informed and educated about organ donation via in
      service training courses, and encourage organ donation by members of society.

PMID- 21094781
TI  - Medical students' knowledge about organ transplantation: a South African
      perspective.
AB  - BACKGROUND: Educating physicians about transplantation during undergraduate
      training can improve organ procurement rates. The aim of this study was to
      evaluate and analyze the knowledge of medical students regarding transplantation.
      METHODS: A previously validated self-administered anonymous questionnaire was
      distributed to all medical students. RESULTS: Of the 346 participants, 217 (63%)
      were preclinical students. Their mean age was 21 years (range, 18-33) and 62%
      were women. Twenty-nine (8%) students were registered as organ donors. One third
      of all study participants received formal transplantation teaching; a greater
      proportion of clinical students received teaching compared with the preclinical
      group (52% vs 22%, P < .05). Knowledge was frequently reported for kidney (88%),
      liver (81%), bone marrow (78%), and heart (76%) transplantation. Small Intestine
      (13%), pancreas (9%), and pancreatic islets (4%) were the least recognized
      organs/tissues. Ninety-six percent and 62% of respondents were aware of kidney
      and liver living-donor transplants, respectively; the 27% of students with an
      interest in a surgical career had better knowledge of living-donor
      transplantation (P < .05). Only 22 (6%) students knew which solid organ
      transplants were performed in South Africa. CONCLUSION: Medical students have
      limited knowledge about organ transplantation; there is a need for educational
      intervention early in the medical curriculum.

PMID- 21094782
TI  - Histopathologic evaluation of pretransplantation biopsy as a factor influencing
      graft function after kidney transplantation in 3-year observation.
AB  - BACKGROUND: Many factors affect long-term results in kidney transplantation
      including histologic damage as a independent predictor, eg, chronic allograft
      dysfunction (CAD) in protocol biopsies and age-dependent lesions. Histopathologic
      findings correlate with the incidence of delayed graft function, eventual renal
      function, and allograft survival, allowing a rather precise prediction of graft
      outcomes. PATIENTS AND METHODS: We analyzed 92 thick-needle preimplantation renal
      biopsies and 29 from grafts after explantation. They had been preserved in 4%
      formalin and immersed in paraffin. Evaluable specimens contained >=10 glomeruli
      and >=2 arterial cross-sections. We analyzed tubulitis, intensity of acute
      tubular necrosis (ATN), inflammatory infiltration, glomerulonephritis, arterial
      hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis,
      increased mesangial matrix, and glomerulosclerosis percentage, although for
      comparative analysis not only optimal ones were taken into consideration. Over
      postoperative time, we analyzed patient condition, urine output, serum
      concentrations of creatinine, urea, uric acid, and ions as well as necessity for
      postoperative dialysis, ie, delayed graft function (DGF). During the 3-year
      observation we analyzed living recipients, graft loss, death with a functioning
      graft, incidence of dysfunction (CAD), and acute rejection episodes (ARE).
      RESULTS: We observed significant correlations between immediate graft function
      (IGF) and lack of ATN in the pretransplantation biopsy. The presence of ATN
      significantly correlated with DGF and primary graft non-function. There was no
      correlation between renal function and arterial hyalinization or fibrosis,
      inflammatory infiltration, and tubular atrophy. Over postoperative time we
      observed significant correlations between IGF and the lack of interstitial
      fibrosis as well as significantly lower levels of creatinine, urea, and potassium
      as well as greater urine output early after transplantation. IGF correlated with
      shorter time to reach a creatinine level of 2 mg/dL, lower concentrations of
      creatinine, urea, and potassium, as well as greater diuresis during the first 5
      days. In addition, lower creatinine and urea concentrations after 1 month and of
      urea at 6 and 36 months were associated with IGF. Female recipients showed lower
      concentration of creatinine over 3 months, of urea during the 1st day, and of
      potassium at 1 month; however, thereafter the differences were not significant.
      Better function of the right kidney was observed. The presence of severe ATN (ATN
      III) correlated with lower creatinine concentrations at 6 months and urea after 3
      years. The presence of hyalinization in biopsies correlated with higher
      concentrations of urea at 1 year and of borderline significance after 3 years;
      surprisingly, potassium concentrations were lower after 2 and 3 years. The
      presence of inflammatory infiltrates correlated with higher creatinine
      concentrations after 1 and 3 years; similar correlations, albeit of borderline
      significance, were observed in tubular atrophy. Interstitial fibrosis correlated
      with creatinine concentrations during 10 days after the operation and after 12
      months, also with potassium concentrations 5 days after the operation. Borderline
      correlations were observed between donor age and creatinine concentration in the
      first day after the operation, after 6 months, and time to achieve a creatinine
      concentration of 2 mg/dL. We observed that biopsies with greater numbers of
      glomeruli correlated with better graft function, namely, lower creatinine
      concentrations after 5 days as well as at 1 and 6 months, as well as lower urea
      concentrations after 5 days and 6 months. We also observed differences in renal
      function depending on gender. The presence of acute tubular necrosis, arterial
      fibrosis and a lack of inflammatory infiltration in pretransplantation biopsy
      correlated with worse late renal function. Explantation biopsies showed signs of
      CAD in 66.4% and histologic features of ARE in 38.51%.

PMID- 21094783
TI  - Results of kidney transplantation from high-terminal creatinine donors and the
      role of time-zero biopsy.
AB  - BACKGROUND: Deceased-donor kidney transplantation (DDKT) from high-terminal
      creatinine donors is associated with lower graft survival. These kidneys may be
      considered for discarding, worsening the organ shortage crisis. Using time-zero
      biopsy for histologic evaluation of these kidneys, we identified those organs
      eligible for transplantation, seeking to achieve better graft utility with
      comparable outcomes. METHODS: From April 2004 to April 2008, 55 patients
      underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis,
      interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring
      system was used to determine a discard. RESULTS: Twenty-five patients received
      DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal
      creatinine, HTC group) and 30 from donors whose terminal creatinine levels were
      <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys
      from HTC donors had shorter waiting times (P = .011) but a higher incidence of
      delayed graft function after transplantation (P < .001). Nonetheless, 5-year
      graft survival rates were similar between the two groups. CONCLUSIONS: With a
      time-zero biopsy for histologic evaluation, kidneys recovered from high-terminal
      creatinine donors can be transplanted to overcome the organ shortage while
      achieving reasonable graft survival.

PMID- 21094784
TI  - The influence of intraoperative central venous pressure on delayed graft function
      in renal transplantation: a single-center experience.
AB  - INTRODUCTION: Delayed graft function (DGF) is a common complication in kidney
      transplantation. We sought to evaluate possible correlates for DGF including
      intraoperative parameters, focusing on fluid replacement and central venous
      pressure (CVP) values among patients undergoing kidney transplantation at our
      center. METHODS: One hundred fifty-five cadaveric donor transplantations
      performed at our center between 2001 and 2005 were selected for the study. We
      compared intraoperative parameters together with 15 other clinical and socio
      demographic recipient and donor variables among patients experiencing DGF (n =
      58) versus those with immediate graft function (IGF; n = 97). All significant
      variables at P < .05 upon univariate analysis were entered into a multivariate
      logistic regression model to identify risk factors for DGF. RESULTS: CVP at
      awakening of <=8 mm Hg (odds ratio [OR] = 3.53; 95% confidence interval [CI],
      1.63-7.63), fluid input during surgery <=2.250 mL (OR = 2.12; 95% CI, 1.00-4.51),
      and recipient age >=50 years (OR = 2.72; 95% CI, 1.11-6.68) were the strongest
      correlates of DGF. CONCLUSIONS: Our data suggested that reduced intraoperative
      perfusion as measured using CVP monitoring might increase DGF risk. This study
      provides the rationale to further investigate the optimal CVP target during this
      surgery.

PMID- 21094785
TI  - Biliary complications after orthotopic liver transplantation from donors after
      cardiac death: broad spectrum of disease.
AB  - BACKGROUND: Donation-after-death liver transplantation (DCD-LT) carries higher
      complication rates compared with donation-after-brain death liver transplantation
      (DBD-LT). In this report we describe our experience with biliary complications in
      DCD-LT with emphasis on anatomical patterns and outcomes. MATERIALS AND METHODS:
      We performed retrospective review of patients' medical records from August 2004
      to December 2008, during which time total of 26 DCD-LTs were performed. Mean
      follow-up was 29 months (range 3 to 51 months). RESULTS: Biliary complications
      occurred in 12 patients (46%), of whom 9 were related to DCD (35%). Four patients
      had more than 1 biliary complication, and 4 had concomitant arterial problems
      (stricture/thrombosis). Treatment of complications included: ERCP (n = 5, 3
      resolved), conversion to roux (n = 5, 2 resolved), revision of roux (n = 1),
      percutaneous transhepatic cholangiography (n = 1), artery revision (n = 3). Three
      patients with casts had operative extraction of casts depicting a mummified
      biliary tree; histology showed casts and fibrosis and anastomotic suture
      material. Six patients underwent retransplantation (23%). Among retransplanted
      patients, 2 deaths occurred (7.7%). CONCLUSION: Our experience with DCD-LT
      reveals a high prevalence of biliary complications with a new and wide spectrum
      of clinicopathologic findings. Better strategies for prevention of these unique
      biliary complications are needed to better justify the added risks and costs for
      performance of DCD-LT.

PMID- 21094786
TI  - Stem cell factor, interleukin-16, and interleukin-2 receptor alpha are predictive
      biomarkers for delayed and slow graft function.
AB  - INTRODUCTION: Delayed graft function (DGF) and slow graft function (SGF) due to
      ischemic and reperfusion injury (IRI) are common complications of deceased donor
      kidney transplantation. We tested whether a panel of serum and urine cytokines
      represent early biomarkers for DGF and SGF. METHODS: We collected serum and urine
      samples from 61 patients 48 hours posttransplantation and used a multiplex enzyme
      linked immunosorbent assay (ELISA) technique to measure levels of 23 cytokines.
      Fourteen patients developed poor graft function (PGF), with 6 having DGF and 8
      with SGF. RESULTS: Area under receiver operation characteristics curve (AUC)
      demonstrated the following: serum levels of SCF (0.88) and interleukin (IL) 16
      (0.74). CONCLUSIONS: This study showed that a select panel of cytokines measured
      early post kidney transplantation may predict poor graft function.

PMID- 21094787
TI  - Role of transcription factors in small intestinal ischemia-reperfusion injury and
      tolerance induced by ischemic preconditioning.
AB  - BACKGROUND: Small intestinal ischemia-reperfusion (I/R) injury, a clinically
      important condition, induces severe organ damage. Ischemic preconditioning (IPC)
      produces tolerance to long-term I/R by inducing a short-term I/R. Herein, we have
      examined the reduction in the extent of injury by IPC. METHODS: Small intestinal
      I/R injury was induced in rats by clamping the superior mesenteric artery (SMA)
      for 30 minutes followed by reperfusion for various 30 minutes. The IPC + I/R
      group underwent a short-term I/R (IPC) prior to long-term I/R. Nuclear factor
      kappaB (NF-kappaB) activity was analyzed by an electrophoretic mobility shift
      assay and cytokine mRNA levels, by reverse transcription-polymerase chain
      reaction. Apoptosis-related genes were analyzed by Western blotting and
      immunohistochemistry, and apoptotic cells, by TUNEL staining. RESULTS: The
      animals were subjected to 30 minutes of ischemia followed by 30 minutes of
      reperfusion. NF-kappaB activity increased in the I/R group and decreased in the
      IPC + I/R group. The IPC + I/R group showed decreased cytokine in mRNA levels.
      Expression of the proapoptotic gene caspase-3 was increased in the I/R and
      decreased in the IPC + I/R group. Expression of the antiapoptotic gene Bcl-xL was
      increased in the IPC + I/R group. The number of apoptotic cells was increased in
      the I/R and decreased in the IPC + I/R group. CONCLUSION: Small intestinal I/R
      injury was reduced by IPC produced by clamping the SMA; thus, IPC may have
      potential clinical applications in the future.

PMID- 21094788
TI  - Effect of necrosis modulator necrox-7 on hepatic ischemia-reperfusion injury in
      beagle dogs.
AB  - OBJECTIVE: The liver is susceptible to ischemia-reperfusion (IR) injury during
      inflow occlusion for hepatectomy. There is no effective pharmacologic agent
      available to prevent the release of high-mobility-group box 1 (HMGB1) or to
      ameliorate IR injury. This pilot study sought to develop a model in beagle dogs
      for the purpose of testing the efficacy of a necrosis modulator, necrox-7, to
      prevent hepatic IR injury in beagle dogs. METHODS: Six male beagle dogs were
      randomly assigned to the control group (group A; n = 3) or the treatment group
      (group B; n = 3). Under general anesthesia, group B received intravenous infusion
      of necrox-7 (13 mg/kg over 20 minutes) followed by 60 minutes of left hepatic
      inflow occlusion and 60 minutes of reperfusion. Both groups were tested for serum
      biochemicals, hematology values, liver biopsies, and plasma HMGB1 levels over a
      48-hour period. RESULTS: The maximum alanine transferase (ALT), aspartate
      transferase (AST), and lactate dehydrogenase (LDH) levels among group A versus
      group B were: ALT 868.3 +/- 337.4 IU/L vs 274.3 +/- 72.6 IU/L (P = .041); AST
      1,024.7 +/- 246.5 IU/L vs 505.3 +/- 66.7 IU/L (P = .024); and LDH 962.7 +/- 226.2
      IU/L vs 552.7 +/- 62.4 IU/L (P = .039). Liver biopsy demonstrated marked necrosis
      and inflammatory infiltrates in group A, whereas group B showed little evidence
      of IR injury. The plasma HMGB1 concentration was significantly lower among group
      B versus A. CONCLUSION: This pilot study developed a hepatic IR injury model,
      demonstrating that necrox-7 reduced hepatic necrosis secondary to IR injury in a
      large animal setting.

PMID- 21094789
TI  - Liver injury following renal ischemia reperfusion in rats.
AB  - INTRODUCTION: All transplanted solid organs experience some degree of ischemia
      reperfusion (I-R) injury. There is some evidence that I-R injury affects remote
      organs. We investigated the effects of renal I-R injury on hepatic function,
      cytochrome P-450 enzymes, and morphology in rats. METHODS: A rat model of 1 hour
      of renal ischemia followed by 1, 4, or 8 hours of reperfusion. The assays
      included serum alanine aminotransferase (sALT) aspartate aminotransferase (sAST),
      cytochrome P-450 enzymes (CYP3A, CYP2E1), hepatic glutathione S-transferase
      (GST), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and
      myeloperoxidase (MPO) activities. In addition, we measured serum blood urea
      nitrogen (BUN) and serum creatinine (SCr), and renal MDA, glutathione peroxidase
      levels, and SOD activities. Morphological liver changes were observed by optical
      and electron microscopy. RESULTS: sALT and sAST significantly increased after 1
      hour of ischemia and 4 or 8 hours of reperfusion. Hepatic CYP3A and CYP2E1
      activities were significantly decreased after 1 hour of ischemia and 1 or 4 hours
      of reperfusion. Hepatic GST, GSH, and SOD activities decreased after renal I-R,
      while MDA levels and MPO increased. Serum BUN and SCr levels significantly
      increased after reperfusion. Changes in renal MDA, GSH-px, and SOD activities
      were similar to those in the liver. The only difference between them was the peak
      time of injury: for the kidney, 8 hours, while for the liver, some changes
      appeared at 4 hours. Optical microscopy showed hepatic passive venous congestion
      and fatty degeneration as well as local necrosis. Transmission electronic
      microscope showed hepatic cell membrane was damaged, which seemed to explain some
      data results above. For example, the release of hepatic ALT and AST increased
      serum ALT and AST. More importantly, the release of neutrophil chemokine induced
      neutrophil accumulation in the liver, which could cause further damage.
      CONCLUSION: Our findings indicated that hepatic function, cytochrome P-450
      enzymes and morphology were affected by renal I-R injury. These effects seemed to
      be mediated in part by an imbalance of oxidant and antioxidant systems and
      recruitment of neutrophils to the liver.

PMID- 21094790
TI  - Functional and histological comparison of rat liver preserved in University of
      Wisconsin solution compared with tissue preserved in a novel solution.
AB  - An isolated perfused rat liver model was used to investigate biochemical and
      histologic changes during 2 hours of reperfusion after 24 hours of cold storage
      to compare Leeds solution (LS) with University of Wisconsin solution (UW).
      Compared with livers stored in UW, those perfused with LS showed significantly
      higher bile flow and lower enzyme production (P < .05 by 1-way analysis of
      variance). For example, after 120 minutes, alanine aminotransferase results were:
      LS 38.9 U/L vs UW 66.8 U/L and bile flows were LS 10.3 MUg/15 min/g liver vs UW
      9.2 MUg/15 min/g liver. Histologically the reticulin breakdown was greater and
      its reformation slower in UW-preserved livers. Liver tissue was viable in both
      groups, as shown by the increased glycogen content after reperfusion in both
      groups, but seen at a higher rate among LS, perfused livers. In conclusion, LS
      compared favorably with UW to prevent ischemic damage and so could offer an
      alternative perfusion medium to UW.

PMID- 21094791
TI  - Role of multidetector-row computed tomography in evaluation of living renal
      donors.
AB  - OBJECTIVES: To assess the value of multidetector-row computed tomography (MDCT)
      in evaluation of the anatomy of living kidney donors and to reveal the prevalence
      of renal vascular variations in a Chinese population. PATIENTS AND METHODS: One
      hundred four potential donors underwent MDCT, and the data sets were
      postprocessed for reformatted images using maximum intensity projection, a volume
      rendering technique, and multiplanar re-formation. Nephrectomy was performed in
      97 donors, which enabled correlation of MDCT evaluation with the actual anatomy
      at surgery as the standard of reference. RESULTS: The MDCT images accurately
      demonstrated the anatomical structure of the main renal arteries and veins and
      the upper part of the ureters. The prevalence of accessory arteries was 41.7% (43
      of 103), and of early branching was 12.6% (13 of 103). Compared with findings
      during surgery, the detection rate of accessory arteries on MDCT images was 91.3%
      (21 of 23), of larger accessory arteries (>1.5 mm in diameter) was 100%, and of
      early branching was 100%. CONCLUSION: Multidetector-row computed tomography is
      helpful in accurately evaluating the renal anatomy of potential donors, thus
      facilitating planning of surgery.

PMID- 21094792
TI  - Audit of an initial 100 cases of laparoscopic live donor nephrectomy.
AB  - BACKGROUND: The objective of this study was to analyze variables related to the
      surgical technique and postoperative evolution of kidney donors. MATERIALS AND
      METHODS: This retrospective analysis describes 100 laparoscopic nephrectomies
      from living donors performed in our hospital between February 2002 and July 2007.
      The variables were age, family relationship, surgical time, warm ischemia time,
      hospital stay, oral feeding resumption, morphine use, return to work, and
      complications. RESULTS: The average age of the donors was 49.5 years and their
      male:female ratio was 1:2. The left kidney was extracted from 82% of patients.
      The warm ischemia time was 2.5 minutes (range = 1.09-5.10). There was only one
      case of multiple vessels. The surgical time was 149.5 minutes (range = 80-255).
      The mean hospital stay was 4.8 days (range = 1-18). Food intake was resumed after
      24 hours, with morphine needed for 0.9 days. The time to return to work was 39
      days (range = 7-120). The complications included kidney rupture (n = 1), liver
      tear (n = 1), hematoma (n = 6), including four requiring blood transfusions;
      fever and leukocytosis (n = 5) and one collection. No patients died as a result
      of the surgery. CONCLUSIONS: Living-donor laparoscopic nephrectomy constitutes
      the gold standard among surgical options.

PMID- 21094793
TI  - Technical modifications of retroperitoneoscopic live donor nephrectomy: Chinese
      experience.
AB  - OBJECTIVE: The objective of this article is to report a single-center experience
      and technical modifications of retroperitoneoscopic live donor nephrectomy
      (RPLDN). MATERIALS AND METHODS: One hundred twenty-one 3-port RPLDNs were
      performed at our institution. No prisoners or organs from prisoners were used to
      collect the data for this study. The tributaries of renal artery and vein were
      transected using a harmonic scalpel after both ends of the tributary were
      coagulated intermittently until the color turned light yellow. Transection was
      made using shifting coagulation. A longitudinal 6-8-cm skin incision was extended
      inferiorly from the primary trocar with muscles intact. The renal artery was
      clipped using two Hem-o-Lok clips at the proximal end, and then sheared by
      scissors without any clips on the kidney side. The renal vein was controlled
      similarly. The graft was retrieved by insertion of a hand through the
      longitudinal lumbar incision. RESULTS: The mean operative time and warm ischemia
      time were 126.1 and 3.6 minutes, respectively. No blood transfusion or open
      conversion was required. None of the donors encountered a major complication, but
      7 suffered minor complications. Preoperative and postoperative mean serum
      creatinine levels of the donors were 1.00 and 1.29 mg/dL, respectively. The mean
      serum creatinine levels of the recipients postoperatively at day 1 and month 1
      were 5.48 and 1.60 mg/dL, respectively. CONCLUSIONS: The modified approach of
      RPLDN may be a useful alternative with flexible control of the renal vessels and
      tributaries and easy retrieval of the graft.

PMID- 21094794
TI  - Osteoprotegerin and progression of coronary and aortic calcifications in chronic
      kidney disease.
AB  - Vascular calcifications (VCs) are important predictors of cardiovascular
      mortality in patients with chronic kidney disease (CKD). We have shown previously
      that osteoprotegerin (OPG), a potential early biomarker for VC, was an
      independent predictor of mortality in CKD patients. The aim of our study was to
      follow longitudinally coronary and aortic VCs. VCs were measured using Siemens 16
      detector CT in a group of predialysis and hemodialyzed patients before and after
      a follow-up of 4 years. Some of these patients were transplanted in the meantime.
      Renal function, calcium, phosphate, iPTH, hs-CRP (high sensitive protein C
      reactive), and OPG serum levels were also compared. VCs progressed in
      predialysis, hemodialyzed, and transplanted patients but the progression was not
      the same in all arterial beds. A progression of coronary calcifications was
      observed in predialysis and transplanted patients, while aortic calcifications
      worsened significantly only in hemodialyzed patients. OPG serum levels and hs-CRP
      were significantly lower among transplanted patients. We concluded that VC
      depends on the severity of the kidney disease. Transplanted patients are not
      protected from VC, yet their OPG serum levels were significantly lower,
      suggesting that there is no link between between OPG levels and severity of VC.
      Longer follow-up of these patients would be necessary to assess whether a decline
      in OPG correlates with better survival.

PMID- 21094795
TI  - Presence of cardiovascular disease in patients on a waiting list for renal
      transplantation and in patients after kidney transplantation in a single center.
AB  - BACKGROUND: Cardiovascular risk in hemodialysis patients is enhanced, resulting
      in a higher mortality rate compared with the general population, yet the average
      wait time for renal transplantation in Germany is 5-7 years. The age of wait
      listed patients has risen progressively. The aim of this study was to evaluate
      the prevalence of cardiovascular disease in patients on the waiting list in our
      center before and after renal transplantation as well as the extent to which
      invasive treatment was required in these patients. METHODS: The study
      investigated 2 groups: 350 patients on the renal transplantation waiting list at
      our center in 2008 and 324 patients who underwent renal transplantation at the
      same center in the years 2003-2007. RESULTS: In 2008, 141 women and 209 men with
      a mean age of 48.6 years (range 13-71 years) were on the waiting list. In the
      years 2003-2007, 98 women and 226 men with a mean age of 54.3 years (range 16-78
      years) received renal transplants. One hundred six patients on the waiting list
      for renal transplantation had to undergo coronary angiography. There is no upper
      age limit for donors or recipients in our program. Mean age at admission on the
      waiting list was 48.6 years (range 13-71 years). Mean age at transplantation was
      54.3 years (range 16-78 years) in our center. Most of these patients were
      asymptomatic but presented a risk profile that included diabetes mellitus, severe
      general atherosclerosis, a pathologic ergometric test, or abnormal myocardial
      scintigraphy. Only in 1 case could coronary heart disease be excluded. Seventy
      patients (20%) suffered from mild to moderate coronary heart disease without the
      need for intervention. In 5 patients (1.4%) coronary bypass surgery was necessary
      due to severe 3-vessel coronary heart disease. In 2 cases (0.6%) replacement of
      the aortic valve was performed because of aortic valvular stenosis. Coronary
      angioplasty without implantation of stents was done in 2 patients (0.6%). Twenty
      two patients (6.8%) were treated with implantation of bare metal stents and 6
      patients (1.7%) with drug-eluting stents. After renal transplantation, 22
      patients (6.8%) suffered from peripheral arterial occlusive disease. In 58
      patients, coronary heart disease was documented by angiography. 16 patients
      (4.9%) had 1-vessel disease, 23 patients (7%) 2-vessel disease, and 19 patients
      (5.8%) 3-vessel disease. Myocardial infarction was documented in 18 patients
      (5.5%) before and in 5 patients (1.5%) after renal transplantation. Bare metal
      stent implantation was performed in 6 patients (1.8%) after transplantation. One
      patient received a drug-eluting stent after renal transplantation. In the years
      2003-2007, 22 patients underwent coronary bypass surgery before kidney
      transplantation. CONCLUSION: The prevalence of coronary heart disease is high in
      patients on the waiting list and after renal transplantation. The majority of
      these patients are clinically asymptomatic. One-third of the patients with
      coronary heart disease had to be treated invasively. Nevertheless, many diabetic
      patients are very sick from multiple complications after the waiting time, making
      theme unsuitable for transplantation.

PMID- 21094796
TI  - Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of
      tacrolimus in Chinese renal transplant recipients.
AB  - The aims of this study were to investigate the influence of CYP3A5 and MDR1
      genetic polymorphisms on tacrolimus pharmacokinetics in Chinese renal transplant
      recipients, so as to help rational administration in clinical practice. We
      calculated pharmacokinetic parameters of tacrolimus from blood concentrations in
      steady state at day 28. Polymerase chain reaction restriction fragment length
      polymorphisms were used for CYP3A5 and MDR1 analysis. The results showed that the
      dose-adjusted area under the concentration time curve (AUC(0-12)) and renal
      clearance showed a significant difference between CYP3A5*1 carriers and the
      CYP3A5*3/*3 genotype (P < .01). In the following study, a distinction was made
      between carriers of CYP3A5*1/ vs CYP3A5*3/*3 seeking to investigate the influence
      of the MDR13435T>C polymorphism on tacrolimus pharmacokinetics. MDR1 3435T>C
      polymorphism did not affect any tacrolimus pharmacokinetic parameter in either
      group. Renal transplant recipients who were CYP3A5*1 carriers required a higher
      dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose
      adjusted AUC(0-12) of tacrolimus. In contrast, MDR1 3435T>C polymorphism was not
      an important factor in tacrolimus pharmacokinetics. Pharmacogenetic methods may
      be used prospectively to aid dose selection and individualize immunosuppressive
      therapy.

PMID- 21094797
TI  - Value of CYP3A5 genotyping on determining initial dosages of tacrolimus for
      Chinese renal transplant recipients.
AB  - Optimal blood levels of tacrolimus in transplant recipients are critically
      important to preserve the allograft. Suboptimal doses of the immunosuppressant
      can result in allograft toxicity or rejection. In the present study, we
      determined CYP3A5 genotypes of patients and analyzed their medical documents in 2
      successive periods. In the first period, a fixed initial dosage of 0.1 mg/kg was
      prescribed daily for 28 patients regardless of their CYP3A5 genotype. In the
      second period, CYP3A5 genotyping was performed with polymerase chain reaction
      restriction fragment length polymorphism and DNA sequencing. The frequency
      distribution of CYP3A5 genotypes was 47.4% (38/78) for *1/*3, 2.6% (2/78) for
      *1/*1, and 50% (39/78) for *3/*3. The patients with *1/*3 had shown significantly
      lower tacrolimus blood levels than those with the *3/*3 when the initial dose of
      0.10 mg/kg was given for 2 weeks postoperatively. In the second period, initial
      dosages were selected according to individuals' CYP3A5 genotypes, 0.08 mg/kg/d
      for recipients with CYP3A5 *3/*3 and 0.15 mg/kg/d for recipients with *1/*3.
      Adjustment of the initial dosage of tacrolimus was documented to improve the
      proportion of patients achieving target drug blood levels in the early
      postoperative stage: from 46.7% to 81.8% of the *1/*3 group and from 46.2% to
      73.1% of the *3/*3 group on the third day. In conclusion, CYP3A5 polymorphism
      plays an important role in influencing tacrolimus blood levels. Initial
      tacrolimus dosage selection based on CYP3A5 genotyping can improve drug blood
      levels in the early stage following renal transplantation.

PMID- 21094798
TI  - HLA-B27 is a potential risk factor for posttransplantation diabetes mellitus in
      autosomal dominant polycystic kidney disease patients.
AB  - The aim of this work was to investigate HLA phenotype predisposition to
      posttransplantation diabetes mellitus (PTDM) in kidney transplant recipients
      stratified according to kidney failure etiology. Ninety-eight transplant
      recipient pairs with kidney grafts from the same cadaveric donor were qualified
      for the study. In each pair, 1 kidney was grafted to an individual with autosomal
      dominant polycystic kidney disease (ADPKD group) and 1 to recipient with a
      different cause of kidney failure (non-ADPKD group). All class II HLA antigens
      were determined with the PCR-SSP molecular method. To identify class I HLA
      molecules we used both molecular and serologic methods. Diabetes was diagnosed
      according to the American Diabetes Association criteria. The posttransplantation
      observation period was 12 months. In the ADPKD group, HLA-B27 was more common in
      PTDM than non-PTDM patients; 31.6% versus 11.4% (P = .069). The difference
      achieved significance when comparing insulin-treated with non-insulin-treated
      patients (44.4% vs 12.4%; P = .029). In the non-ADPKD group, HLA-A28 and HLA-B13
      were observed more frequently in patients with PTDM than in recipients without
      diabetes (22.2% vs 2.5% [P = .0099] and 22.2% vs 3.8% [P = .020]). All of these
      associations were significant upon multivariate analysis. HLA-B27 allele is a
      factor predisposing ADPKD patients to insulin-dependent PTDM. Antigens
      predisposing to PTDM among kidney graft recipients without ADPKD include HLA-A28
      and B13.

PMID- 21094799
TI  - The clinical importance of flow cytometry crossmatch in the context of CDC
      crossmatch results.
AB  - BACKGROUND: The complement-dependent microcytotoxicity crossmatch (CDCXM) is a
      standard method for evaluating the presence of preformed antibodies before
      transplantation. The flow cytometry crossmatch (FCXM) is more sensitive, but
      there is controversy regarding translation of its increased sensitivity to
      clinically relevant graft outcomes. METHODS: We analyzed Organ Procurement and
      Transplant Network registry data for living and deceased donor kidney transplants
      performed in 1995 to 2009 after both CDCXM and FCXM testing. Transplants with
      negative CDCXM (CDCXM(-)) and with T-cell positive (T(+)), T-cell negative/B-cell
      positive (T(-)B(+)), or T- and B-cell negative (T(-)B(-)) FCXM results were
      included. Graft survival according to crossmatch results was compared by survival
      analysis. RESULTS: Among patients transplanted with negative CDCXM (CDCXM(-)),
      deceased and living donor graft recipients with T(+) FXCM experienced significant
      absolute reductions in 5-year graft survival of 11.5% and 8.8% compared to those
      with T(-) FCXM (P < .0001). Compared to patients with FCXM(-)/CDCXM(-) deceased
      and living donor recipients with T(-)B(+) FCXM/CDCXM(-) had absolute reductions
      in 5-year graft survival of 9.6% and 7.6%, respectively (P < .0001). Upon
      multivariate adjustment with Cox regression, T(+) FCXM/CDCXM(-) deceased donor
      transplantation was associated with 51% higher adjusted relative risk of 1-year
      graft loss than FCXM(-)/CDCXM(-). Relative risks were more marked at 1 year for
      the T(+) groups but stronger in the 1- to 5-year interval for the T(-)B(+)
      groups. CONCLUSION: Positive FCXM has important prognostic implications even when
      CDCXM is negative. Thus, positive FCXM should not routinely be dismissed as
      "overly sensitive" when CDCXM is negative.

PMID- 21094800
TI  - Biomarkers for the diagnosis of the stable kidney transplant and chronic
      transplant injury using the ProtoArray(r) technology.
AB  - Transplant glomerulopathy (TG), a form of chronic renal transplant rejection,
      carries a poor prognosis. It must be differentiated from the entity defined by
      the Banff '05 classification, interstitial fibrosis/tubular atrophy (IF/TA).
      Sequential transplant biopsies have shown that these lesions are subclinical long
      before clinical manifestations. The availability of biomarkers may provide an
      earlier diagnosis and subsequent treatment. The aim of our study was to identify
      serum biomarkers in kidney recipients showing TG compared with IF/TA or stable
      patients, using protein microarray technology. This technology detects auto- or
      alloantibodies in patient sera. With a high degree of statistical significance,
      we identified 18 antibody reactivities specific for TG; 11 for IF/TA; and 10
      among stable patients. Target proteins were involved in signal transduction,
      transcription regulation, DNA replication and repair, cell cycle, endocytosis,
      cell redox, as well as glycolysis. Some markers, such as podocan and collagen
      XXIII among TG and tubular cell ion channels among IF/TA, possibly provide
      insights into the pathogenesis of the lesions.

PMID- 21094801
TI  - Vimentin expression and myofibroblast infiltration are early markers of renal
      dysfunction in kidney transplantation: an early stage of chronic allograft
      dysfunction?
AB  - INTRODUCTION: The objective of this study was to show the morphologic
      characteristics of allograft renal biopsies in renal transplant patients with
      stable renal function, which can potentially be early markers of allograft
      dysfunction, after 5 years of follow-up. METHODS: Forty-nine renal transplant
      patients with stable renal function were submitted to renal biopsies and
      simultaneous measurement of serum creatinine (Cr). Histology was evaluated using
      Banff scores, determination of interstitial fibrosis by Sirius red staining and
      immunohistochemical study of proximal tubule and interstitial compartment (using
      cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated
      according to the presence or absence of the epitheliomesenchymal transition
      (EMT). The interstitial presence of myofibroblasts and tubular presence of
      vimentin was also analyzed simultaneously. Renal function was measured over the
      follow-up period to estimate the reduction of graft function. RESULTS: Median
      posttransplant time at enrollment was 105 days. Patients were followed for 64.3
      +/- 8.5 months. The mean Cr at biopsy time was 1.44 +/- 0.33 mg/dL, and after the
      follow-up it was 1.29 +/- 0.27 mg/dL. Nine patients (19%) had a reduction of
      their graft function. Eleven biopsies (22%) had tubulointerstitial alterations
      according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen
      biopsies (32%) had high interstitial expression of myofibroblasts and tubular
      vimentin. Using Cox multivariate analysis, HLA and high expression of
      interstitial myofibroblasts and tubular vimentin were associated with reduction
      of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015),
      respectively. CONCLUSION: Fibrogenesis mechanisms occur very early after
      transplantation and are risk factors for long-term renal function deterioration.

PMID- 21094802
TI  - High levels of IDO-expressing CD16+ peripheral cells, and Tregs in graft biopsies
      from kidney transplant recipients under belatacept treatment.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme
      that suppresses T-lymphocyte activity. Costimulation blockade through CTLA4lg
      increases IDO in antigen-presenting cells. The suppressive effect of IDO is
      thought to be mediated by Foxp3+CD4+CD25+ regulatory T-cells (Tregs). OBJECTIVE:
      In this descriptive study, we evaluated the percentage of IDO-expressing
      peripheral cell subpopulations as well as Tregs in 27 stable kidney transplant
      recipients receiving either belatacept (LEA29Y), a daughter compound of abatacept
      (CTLA4lg; n = 19) or cyclosporine (n = 8). METHODS: Blood samples were obtained
      at 24 +/- 2 months (belatacept) and 23 +/- 6 months (cyclosporine) of treatment.
      Intracellular IDO was analyzed by flow cytometry in CD14+, CD11c+, CD16+, CD56+,
      and CD8+ cell subpopulations. Tregs were assessed by intracellular Foxp3
      detection in CD4+CD25+ cells. CD3+, CD4+, CD8+, CD20+, CD68+, IDO+, and Foxp3+
      cells were evaluated by immunohistochemistry on graft biopsies obtained
      preimplantation, at 12 months posttransplant, and in subjects with dysfunction
      during the first 12 months. RESULTS: Only percentages of CD16+/IDO+-expressing
      peripheral monocytes were significantly increased among the group receiving
      belatacept. No differences were observed in peripheral Tregs between the groups.
      In contrast, higher percentages of Tregs, CD4+, CD8+, and CD68+ cells were noted
      in dysfunction and at 12 months vs baseline among graft biopsies in subjects
      receiving belatacept, and also among dysfunction cohorts of belatacept vs
      Cyclosporine treatment. CONCLUSION: Patients receiving belatacept showed greater
      amounts of peripheral blood CD16+/IDO+ cells and Tregs on graft biopsies than
      those under cyclosporine treatment.

PMID- 21094803
TI  - Clinical outcome of preemptive kidney transplantation in patients with diabetes
      mellitus.
AB  - End-stage renal disease (ESRD) caused by diabetic nephropathy is increasing
      throughout the world. The survival of diabetic patients treated by
      transplantation has improved nowadays. Although recent studies have demonstrated
      preemptive kidney transplantation to be associated with better graft survival in
      CKD patients, the effect of pre-transplantation dialysis on graft outcomes among
      diabetic ESRD patients is unclear. This analysis summarized our experience with
      preemptive kidney transplantation in diabetic ESRD patients by retrospectively
      comparing 70 such patients transplanted between 1995 and 2009. These 70 patients
      were divided into two groups: 30 patients underwent preemptive and the other 40
      transplantation after maintenance hemodialysis or peritoneal dialysis. We
      compared graft survivals, acute rejection episodes, postoperative complications,
      and delayed graft function rates. The 10-year patient survival of 100% in the
      preemptive group was similar to that of the nonpreemptive group (85%, P = .11).
      But the 10 year graft survival was higher among the preemptive than the
      nonpreemptive group (100% vs 75%, P = .02). Pre-transplantation modality did not
      affect graft survival. Therefore, preemptive kidney transplantation should be
      applied to eligible patients with diabetic ESRD.

PMID- 21094804
TI  - Randomized trial of thymoglobulin versus alemtuzumab (with lower dose maintenance
      immunosuppression) versus daclizumab in living donor renal transplantation.
AB  - BACKGROUND: We performed a randomized trial evaluating alemtuzumab, a humanized
      anti-CD52 monoclonal antibody, in living donor (LD) kidney transplantation.
      METHODS: Thirty-eight LD first renal transplant recipients were randomized into
      three single-agent antibody induction groups: thymoglobulin (group A);
      alemtuzumab (group B); and daclizumab (group C). In groups A and C, target
      tacrolimus trough levels were 6 to 8 ng/mL, with 1 gm mycophenolate mofetil (MMF)
      administered twice daily, and maintenance methylprednisolone. In group B, the
      target tacrolimus trough level was 4 to 6 ng/mL, with 500 mg MMF administered
      twice daily, without methylprednisolone. RESULTS: With 29/38 patients now
      followed beyond 36 months posttransplantation, we observed no graft failures and
      only one death with a functioning graft (in group B). Acute rejection episodes
      were low: 0/13, 1/13, and 1/12 patients in groups A, B, and C. Biopsy-proven
      chronic allograft injury was higher among group B (3/13) versus groups A (0/13)
      or C (0/12; P = .01). Poorer renal function was observed in group B; the mean
      calculated creatinine clearance at 3 months posttransplantation was significantly
      poorer: 63.3 +/- 3.0 versus 85.4 +/- 7.2 and 82.2 +/- 8.2 in groups A and C (P =
      .01). No differences in the incidence of adverse events were observed.

PMID- 21094805
TI  - Acute transplant glomerulopathy is associated with antibody-mediated rejection
      and poor graft outcome.
AB  - Transplant glomerulopathy (TG) is traditionally considered to be a chronic
      entity. However, in our practice we observed patients who presented with features
      of TG as early as 14 days posttransplantation. We investigated the
      clinicopathological features of these cases. During a 4-year period, all patients
      with acute rejection were identified. Charts were reviewed to identify patients
      with antibody-mediated rejection and biopsy features of TG within 6 months
      posttransplantation. Three patients met the above-mentioned criteria. All of them
      had diffuse margination of inflammatory cells in peritubular capillaries in the
      setting of acute renal failure or delayed graft function. Monocyte (CD68
      positive) margination in peritubular capillaries was a common feature. All 3
      patients had donor-specific antibodies and features suggestive of antibody
      mediated rejection. C4d stain in peritubular capillaries was focal and mild or
      absent in serial biopsies. Occlusive endothelial swelling of glomerular capillary
      loops (endotheliosis) preceded TG. None of the patients had evidence for other
      causes of similar glomerular changes in a transplant, such as calcineurin
      inhibitor toxicity, ischemia, hepatitis C, or immune complex glomerulonephritis.
      They did not have other biopsy features of chronicity when TG appeared and as it
      progressed. TG can occur as an acute phenomenon. We propose that endotheliosis is
      a more accurate and specific precursor of TG than mere glomerulitis. These cases
      of acute TG may represent a form of antibody-mediated rejection associated with
      proteinuria and poor response to treatment.

PMID- 21094806
TI  - Low-dose calcineurin inhibitor regimen combined with mammalian target of
      rapamycin inhibitors preserves kidney functions in renal transplant recipients
      without allograft nephropathy.
AB  - OBJECTIVE: The present study was designed to investigate the effect of low-dose
      calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of
      rapamycin (mTOR) inhibitor on renal function in transplant recipients without
      allograft nephropathy. PATIENTS AND METHODS: Twelve patients including seven men
      (58.3%) of overall mean age of 34.8 +/- 14.1 years underwent renal
      transplantation and were switched to a new second-line treatment of low-dose CNI
      combined with an mTOR inhibitor, either sirolimus or everolimus. RESULTS: The
      underlying cause of renal failure was not clear in half of the cases; for the
      others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney
      disease, or hypovolemia. After 6 months of the new therapy, there was a
      significant increase in calculated creatinine clearance levels compared to
      baseline (75.5 +/- 21.9 vs 89.6 +/- 19.1 mL/min; P < .001), but no significant
      change in serum creatinine (1.3 +/- 0.4 vs 1.2 +/- 0.3 mg/dL) or urinary protein
      excretion (187.5 +/- 142.0 vs 394.0 +/- 326.4 mg/g). For almost all patients,
      proteinuria remained stable, but in two patients, it developed but responded to
      enalapril treatment. Dose decrement was required for four patients with
      hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that
      responded to treatment. One patient developed a urinary tract infection that
      responded to antibiotic treatment. None of the patients developed an acute
      rejection episode. CONCLUSION: Low-dose CNI combined with an mTOR inhibitor, as a
      replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium,
      seemed to prevent renal dysfunction for at least 6 months among renal transplant
      patients without allograft nephropathy.

PMID- 21094807
TI  - Outcomes of renal patients from the Ivory Coast transplanted abroad: time for a
      local kidney transplantation program.
AB  - BACKGROUND: The outcomes of transplanted kidney recipients from "transplant
      tourism" have been reported to be alarming. The present study was an attempt to
      examine the results of renal patients from the Ivory Coast transplanted abroad
      returning home for follow-up. PATIENTS AND METHODS: This retrospective analysis
      includes renal patients from the Ivory Coast transplanted abroad between 1995 and
      2009 and followed up by our nephrology clinic. We collected pre- and
      posttransplant parameters for statistical analyses. RESULTS: The 16 patients had
      a median age of 48 years (range = 32.5-53.75). The median age of kidney donors
      was 44 years (range = 30.75-51.25). Initial kidney disease was hypertension in 10
      patients (62.5%) and diabetes in three patients (18.8%). They received organs
      from living donors (37.5% related [LRD] and 37.5% unrelated [LURD]). Initial
      immunosuppression consisted of induction (72.7%), tacrolimus (75%), and
      mycophenolate mofetil (100%). Two patients (12.5%) experienced late acute
      rejections, resulting in graft loss. The overall graft survival was 93% at 1 year
      and 80% at 5 years. Five patients died over the study period, corresponding to an
      overall mortality rate of 9.25/100 patient-years. The overall median patient
      survival was 6.25 years (range = 4.19-7.58). Patient survivals at 1 and 5 years
      were 93% and 53%, respectively. No factors seemed to influence survival (either
      graft or patient) upon multivariate analysis. Comparison between LRD and LURD
      recipients revealed no statistical difference among posttransplant
      characteristics and survivals. CONCLUSION: Mortality of renal patients from the
      Ivory Coast transplanted abroad is high. Financial exhaustion after
      transplantation renders follow-up precarious. A local kidney transplantation
      program in the Ivory Coast appears more urgent than ever.

PMID- 21094808
TI  - When is it reasonable to split pediatric en bloc kidneys for transplantation into
      two adults?
AB  - BACKGROUND: Traditionally, kidneys from donors >=60 years old and pediatric
      kidneys are considered marginal organs for transplantation. Pediatric donor
      kidneys are underutilized for transplantation into adult recipients due to
      concern for poor outcomes. METHODS: Using data from the Organ Procurement and
      Transplant Network, we analyzed patterns of pediatric kidney use (single vs en
      bloc) in the United States from 1987 to 2007. Using the Cox proportional hazards
      model, graft outcomes of pediatric donor kidneys transplanted as single vs en
      bloc grafts from different donor weight groups were compared with renal
      transplantation from donors >=60 years old in an attempt to define a pediatric
      donor weight at which kidneys can be justifiably split to expand the donor pool.
      RESULTS: Compared with older donor kidneys, graft failure risk of pediatric
      single kidneys was consistently lower when the donor weight exceeded 10 kg. On
      the other hand, graft survival benefit for pediatric en bloc kidneys was evident
      starting at donor weight <=10 kg in comparison to older donor kidneys. Pediatric
      en bloc kidneys performed consistently better than pediatric single kidneys for
      all donor weight groups. CONCLUSIONS: Splitting of pediatric donor en bloc
      kidneys for transplantation into 2 adults when the donor weight exceeds 10 kg was
      associated with acceptable graft outcomes. This practice, along with increased
      use of small pediatric donor kidneys, may help to alleviate the waiting list
      burden in renal transplantation.

PMID- 21094809
TI  - The effect of successful kidney transplantation on ventricular dysfunction and
      pulmonary hypertension.
AB  - BACKGROUND: Heart disease is a frequent complication of chronic kidney disease
      and the major cause of death in patients on renal replacement therapy. The
      purpose of this study was to evaluate the impact of successful kidney
      transplantation on systolic and diastolic ventricular dysfunction and pulmonary
      arterial hypertension in patients with chronic kidney disease (CKD). METHODS: The
      study included 35 patients >18 years of age with CKD who had successful kidney
      transplantations. Ventricular function and pulmonary arterial pressure were
      evaluated by echocardiography before and 1 year after transplant. RESULTS: The
      mean age of subjects was 40 +/- 14 years, and 63% were men. Mean left ventricular
      ejection fraction (LVEF) was 52 +/- 16%. Before transplant, 28 (80%) of the
      patients had ventricular dysfunction (34.3% diastolic and 45.7% systolic).
      Pulmonary arterial hypertension was found in 48.6%. Ventricular dysfunction was
      associated with dialysis of >2 years duration before transplant. The LVEF of the
      entire group increased from 52% to 64% (P < .001) by 12 months after kidney
      transplant. Left ventricular diameters, wall thickness, and pulmonary arterial
      systolic pressure decreased significantly after transplantation Echocardiograms
      became normal 1 year after transplant in 8 (66.7%) of the patients with diastolic
      dysfunction and 9 (56.2%) with systolic dysfunction, and diastolic dysfunction
      persisted in 5 (31.2%). CONCLUSIONS: Because kidney transplantation led to
      considerable improvement in left ventricular systolic and diastolic function as
      well as pulmonary arterial pressure of patients with CKD, optimal treatment for
      dysfunction and transplant as soon as possible is recommended.

PMID- 21094810
TI  - Abnormal diurnal rhythm of urine output following renal transplantation: the
      impact of blood pressure and diuretics.
AB  - BACKGROUND: Nocturnal polyuria is the excretion at night of an excessive volume
      of urine. A major problem following renal transplantation is an abnormal diurnal
      rhythmicity in urine output. The purpose of this study was to elucidate the
      prevalence of nocturnal polyuria among renal transplant recipients in the early
      period after transplantation as well as at least 1 year after transplantation. We
      aimed to explore possible pathophysiological mechanisms behind nocturnal polyuria
      in this group of patients, focusing on the impact of blood pressure and
      medication. METHODS: Seventeen recently transplanted patients 17 late transplant
      recipients, and 17 healthy controls were included in the study. Voiding habits
      were assessed by completion of a frequency-volume chart recording all fluid
      intakes and voiding. A concomitant 24-hour blood pressure profile was obtained in
      all. RESULTS: Renal transplant recipients had a high prevalence of nocturnal
      polyuria (74%) and a disturbed blood pressure profile with a lack of appropriate
      nocturnal dipping (P < .0001) compared to controls. We found a positive
      correlation between increased nocturnal blood pressure and urine output at night
      (r = .368, P = .008). Patients taking diuretics had a circadian diurnal rhythm of
      urine output and a blood pressure profile similar to controls. CONCLUSIONS:
      Nocturnal polyuria was very common among both recent and late transplant
      recipients. A high fluid intake during daytime and hypervolemia were suggested as
      causes of a disturbed blood pressure profile, which partly seemed to explain the
      high urine output at night. Daytime diuretics may be an effective treatment of
      this inconvenient complication.

PMID- 21094811
TI  - A prospective protocol-based trial of darbepoetin alfa therapy to correct the
      early anemia following renal transplantation.
AB  - Anemia is a common complication accompanying renal transplantation. The
      evaluation and therapy for posttransplant anemia (PTA) are not standardized and
      remain controversial. This was a prospective, protocol-driven attempt at early
      PTA evaluation and management by transplant nurse coordinators. Between 1 and 2
      months posttransplantation, 75 consecutive recipients were evaluated for the
      presence and causes of anemia. Anemic patients were given standard doses of
      darbepoetin alfa (DA) for 3 months. Response to therapy and patient outcomes were
      evaluated over 15 months. Twenty-five (33%) of all patients were anemic,
      including 32% who were erythropoietin (EPO)-deficient and 68% with relative EPO
      resistance. No patient with early PTA showed an elevated EPO level or increased
      reticulocytes. Predisposing factors for early PTA included increased numbers of
      perioperative transfusions, deceased kidney donor, decrease reticulocyte count,
      and renal insufficiency. DA therapy corrected anemia in 20% of patients at 1
      month and in 60% at 3 months. Patients unresponsive to standard DA doses were
      observed to display reduced renal function and new onset iron deficiency.
      Patients with prolonged PTA may represent a high-risk population requiring more
      intensive medical supervision. Nurses were able to efficiently direct DA therapy
      with only 1.7% protocol violations.

PMID- 21094812
TI  - Prevalence and predictive factors of anemia after renal transplantation: a
      Moroccan report.
AB  - OBJECTIVE: Anemia, a common multifactorial problem in kidney transplant
      recipients, represents an important cardiovascular risk factor. The purpose of
      this study was to assess anemia prevalence after kidney transplantation, the main
      factors involved in its occurrence, its cardiovascular consequences, and its
      impact on patient survival and graft function. METHODS: This retrospective study
      evaluated 69 patients undergoing renal transplantation between January 1998 and
      September 2008 with >=1 year of follow-up. For all of the patients, we recorded
      hemoglobin concentrations before and at 1, 3, 6, 12, 36, and 60 months after
      transplantation. Anemia was defined as recommended by the American Society of
      Transplantation: hemoglobin level <12 g/dL in women and <13 g/dL in men. To
      determine the factors involved in anemia occurrence, we compared 2 groups of
      patients, with versus without anemia, at various times after renal
      transplantation. RESULTS: This study showed a high prevalence of anemia in the
      early posttransplantation period of 82.7% and 42% of kidney transplantation
      patients at 1 month and 6 months, respectively. It was mainly related to a low
      pretransplant hemoglobin level. The prevalence declined to 37.7% at 1 year. Renal
      graft dysfunction was the most important factor in the occurrence of late post
      renal transplantation anemia. The presence of anemia increased the risk of renal
      graft functional deterioration by a factor of 2.9. The decreased prevalence at 1
      year after transplantation was significantly associated with a reduction in left
      ventricular hypertrophy. CONCLUSION: The management of anemia is essential to
      improve renal graft survival, reduce cardiovascular morbidity, and ensure a
      better quality of life for renal transplant recipients.

PMID- 21094813
TI  - Loss of bone mineral density in renal transplantation recipients.
AB  - AIM: This study investigated the prevalence and contributing factors of loss of
      bone mineral density after renal transplantation among Turkish patients. PATIENTS
      AND METHODS: The study included 70 subjects, namely 50 males and 20 females of
      overall mean age of 36.94 +/- 10.09 years. We measured femoral neck mineral
      density by dual-energy X-ray absorptiometry (DEXA). A T score above -1 was
      defined as a normal bone mineral density compared with T scores of -1.0 to -2.5
      or below -2.5 which were defined as either osteopenia or osteoporosis,
      respectively. RESULTS: At a median duration of 23 months after renal
      transplantation, osteopenia or osteoporosis was observed among 30 (42.9%) or 30
      (42.9%) of the 70 patients, respectively. The mean body mass index (BMI) value
      was significantly higher among the normal than the osteoporotic group: 27.59 +/-
      4.66 kg/m(2) vs 24.18 +/- 3.57 kg/m(2), respectively. However, no significant
      differences occurred in terms of BMI among the other groups. The amount of
      proteinuria was significantly lower in the normal than the osteopenic or
      osteoporotic group: (12.5 (range, 10.0-20.0); 105.0 (10.0-2800.0) or 215.5 (10.0
      1880.0) mg/d (P = .001 and .004, respectively). In contrast, there was no
      significant difference between the amounts of proteinuria displayed by the
      osteopenic group and the osteoporotic group (P < .05)]. These patient groups
      showed no difference in age, gender, donor source, cause of end-stage renal
      disease (ESRD), pretransplant dialysis modality, duration of dialysis, use of a
      vitamin D preparation, immunosuppressive regimen, posttransplantation period,
      levels of iPTH or 25 hydroxy vitamin D3 (25OH vit D), exposure to tacrolimus or
      cyclosporine (CyA), calcium * phosphate product, serum albumin and hemoglobin
      content, creatinine clearance, or serum bicarbonate concentrations (P > .05). The
      T scores of the femoral neck correlated with BMI (r: 0.415; P = .001), 25OH vit D
      level (r: 0.268, P = .026), creatinine clearance (r: 0.273, P = .022), and serum
      glucose level (r: 0.349, P = .003). It inversely correlated with the amount of
      proteinuria (r: -0.263, P = .028), serum alkaline phosphatase level (r: -0.329, P
      = .005), and serum magnesium concentration (r: -0.252, P = .035). Upon
      multivariate analysis, BMI and 25OH vit D level were observed to be independent
      risk factors for loss of femoral mineral density. CONCLUSION: Loss of bone
      mineral density is a common complication that correlates with low BMI values and
      decreased 25OH vit D levels as major risk factors for this problem.

PMID- 21094815
TI  - Tumor necrosis factor alpha promoter polymorphism in posttransplantation diabetes
      mellitus of renal transplant recipients.
AB  - Posttransplantation diabetes mellitus (PTDM) is a major complication in renal
      transplant recipients. Some studies have demonstrated that tumor necrosis factor
      alpha (TNF-alpha) expression and its genetic polymorphism are associated with
      diabetes mellitus. We investigated this association in Asian renal transplant
      recipients. Polymerase chain reaction-restriction-fragment length polymorphism
      was used to measure TNF-alpha G-238A and G-308A gene polymorphisms among 241
      nonposttransplantation diabetic subjects and 73 PTDM patients. PTDM patients
      showed higher values of body weight and body mass index (BMI) than the non-PTDM
      group. However, no significant association was observed between TNF-alpha G-238A
      and TNF-alpha G-308A polymorphisms with PTDM incidence, gender, age at
      transplantation, follow-up duration, BMI, or type of immunosuppression.

PMID- 21094814
TI  - Cinacalcet improves bone density in post-kidney transplant hyperparathyroidism.
AB  - The recent availability of cinacalcet has provided a possible alternative to
      parathyroidectomy in kidney transplant patients with persistent
      hyperparathyroidism, but its effect on bone mass density (BMD) is unknown. From
      our database containing 163 kidney transplants performed at our center from 1999
      to 2007, we compared recipients who received cinacalcet for persistent
      hypercalcemia and hyperparathyroidism following renal transplantation (n = 8)
      with up to two other posttransplant patients matched for age, sex, race, and
      graft function (n = 15). The outcome of the study was BMD changes from baseline
      to 12, 24, and 36 months post-renal transplantation. Repeated-measures mixed
      model was used to assess the difference of BMD change between two groups.
      Cinacalcet therapy was started at a median of 9 (range = 1 to 24) months
      posttransplant with a mean dose 56 +/- 29 mg/d (mean duration = 1.6; range = 1 to
      2.1 years). Cinacalcet therapy was associated with significant reduction of serum
      calcium compared to control. Cinacalcet therapy was associated with greater BMD
      increase at the hip over the 36-month posttransplant period. Cinacalcet was well
      tolerated. Our results suggest that cinacalcet may have a small but favorable
      effect on bone density following kidney transplantation.

PMID- 21094816
TI  - Hyperuricemia in kidney transplant recipients with intact graft function.
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence of
      hyperuricemia and factors predicting its occurrence, and to establish the
      relationship over time between serial changes in estimated glomerular filtration
      rate (eGFR) and uric acid (UR) concentration in kidney transplant (KT) recipients
      with eGFR >60 mL/min/1.73 m(2). METHODS: Adult patients who underwent KT at the
      Asan Medical Center between 1990 and 2008 and maintained eGFR >60 mL/min/1.73
      m(2) were retrospectively assessed. Clinical and laboratory data were obtained
      from inpatient and outpatient charts and from the hospital electronic database.
      RESULTS: Of 356 patients, 301 (84.55%) had normal UR levels and 55 (15.45%) had
      hyperuricemia. After multivariate adjustment, transplant duration, male gender,
      eGFR, diabetes mellitus (DM), and calcium level were associated with higher mean
      UR levels. Mean UR level increased significantly and mean eGFR decreased
      significantly during the first year after transplantation, but there were no
      significant differences over the next 4 years. Serial UR and eGFR levels changed
      almost simultaneously. CONCLUSIONS: Transplantation duration, male gender, eGFR
      level, DM, and serum calcium level were risk factors for hyperuricemia in kidney
      recipients with intact graft function. Increased uric acid after KT did not
      significantly affect graft function.

PMID- 21094817
TI  - Serial measurements of hepatitis C viral load by real-time polymerase chain
      reaction among recipients of living-donor renal transplants: a short-term follow
      up study from a single center.
AB  - There is a high prevalence of hepatitis C virus (HCV) infection among
      immunosuppressed patients including renal transplant recipients. The study
      investigated serum viral loads for up to 6 months posttransplantation among these
      patients. Serum viral load was serially monitored using real-time polymerase
      chain reaction (PCR) in 25 HCV-positive renal transplant recipients
      pretransplantation as well as day 10 and 6 months posttransplantation. A liver
      biopsy specimen obtained under vision at the time of transplantation was analyzed
      for viral load as well as for histological changes. There was increased viremia
      at day 10 followed by a significant (2 log) reduction at 6 months
      posttransplantation. Pretransplantation serum and intrahepatic viral load showed
      significant positive correlations (r = 0.727; P = .001), the latter also
      reflecting liver fibrosis score (r = 0.423; P = .05). The findings suggested that
      serum viral load reflects intrahepatic viral load, which in turn correlates with
      liver fibrosis. At 6 months posttransplantation, the modulatory effects of
      immunosuppressive drugs and of the host immune response may lead to a reduced
      viral load.

PMID- 21094818
TI  - Quantiferon-CMV test in prediction of cytomegalovirus infection after kidney
      transplantation.
AB  - Infection with cytomegalovirus (CMV) is a major cause of morbidity and mortality
      in immunosuppressed patients, including organ and bone marrow transplant
      recipients. The majority of CMV disease is caused by reactivation of alatent
      infection rather that by newly acquired virus. Many techniques have been
      currently available to aid in the diagnostics of CMV disease. In this report we
      performed a prospective evaluation of Quantiferon-CMV assay (Cellestis) to
      determine whether the test is predictive of CMV disease. CD8+ T-cell CMV-specific
      immunity was assessed in a longitudinal cohort of 14 kidney transplant
      recipients. According to our data, subjects with higher cellular immune response
      measured with Quantiferon test had a lower risk of manifestation of CMV infection
      than subjects with lower responses. Despite the small number of patients and
      large intra- and interindividual variability of the data in the study, we
      observed the Quantiferon-CMV assay to be a sensitive specific test to detect a
      virus-specific T-cell response. We propose that this assay in combination with
      viral DNA load estimates may prove to be useful to stratify patients at risk of
      CMV disease.

PMID- 21094819
TI  - Preferential adherence to immunosuppressive over nonimmunosuppressive medications
      in kidney transplant recipients.
AB  - Successful kidney transplantation continues to be associated with an increased
      risk of death from cardiovascular disease. Treatment for hypertension,
      hyperlipidemia, and hyperglycemia adds to the pre-existing medication burden of
      immunosuppression. We postulated that patients are selectively adherent,
      preferentially taking some medications and choosing not to take others. To test
      this hypothesis, a random cross-sectional sample of outpatient kidney transplant
      recipients was interviewed by a person previously unknown to them using a
      structured closed-ended interview. Nonadherence was defined as missing any dose
      of medication over the preceding 1 month. By this criteria, 18.4% of patients
      were nonadherent to immunosuppressive medications, whereas 44.9% of patients were
      nonadherent to nonimmunosuppressive medication (antihypertensives, antidiabetic
      agents, and lipid-lowering agents). More patients were selectively nonadherent to
      their nonimmunosuppressive medications than to their immunosuppressive
      medications (P = .028). Patients who were nonadherent to nonimmunosuppressant
      medications were on a higher number of total medications and were more likely to
      be diabetic. We conclude that patients are more likely to miss or change doses of
      nonimmunosuppressive medications than immunosuppressive medications. The
      importance of nonimmunosuppressive medications must also be stressed at clinic
      visits to facilitate adherence to all classes of medication. Whether nonadherence
      to medications that treat cardiovascular risk factors contributes to the
      persistently high cardiovascular death rate in kidney transplant recipients
      remains to be determined.

PMID- 21094820
TI  - Anxiety, depression and emotional profile in renal transplant recipients and
      healthy subjects: a comparative study.
AB  - BACKGROUND: Renal transplantation is a well established treatment for end-stage
      renal disease. However, recipients have been shown to develop emotional distress
      and affective disorders, such as anxiety and depression, associated with a
      compromised quality of life. Some accounts report an improvement of affective
      disorders after transplantation, others draw opposite conclusion. METHODS: The
      present cross-sectional study selected 42 transplant recipients and 42 control
      subjects matched for gender, age, educational background, and marital status.
      Symptoms of anxiety, depression and general emotional profiles were compared
      using the Zung Self-Rating Anxiety Scale, the Beck Depression Inventory (BDI),
      and the Affective Neuroscience Personality Scale (ANPS), a self-report inventory
      that evaluates 6 neurally based affective tendencies: seeking, caring, and
      playfulness (positive affects) and fear, anger, and sadness (negative affects).
      RESULTS: No significant differences were observed between transplanted patients
      and controls in scores for anxiety and depression, as evaluated with Zung and BDI
      scales. However, transplanted patients scored significantly lower than control
      subjects in fear and anger scales and in general negative emotions. Transplant
      recipients did not display any symptom of anxiety or depression, however, a
      significant reduction in negative affect, evaluated through the ANPS scale
      revealed psychological distress. CONCLUSIONS: These findings suggest that
      affective profile in transplanted patients should be more extensively examined to
      review all facets in their mental and emotional assessment, especially regarding
      the role played by this emotional pattern in complying with medical treatment,
      which is well known to be a clinically critical feature of these patients.

PMID- 21094821
TI  - Patterns of injury in mycophenolate mofetil-related colitis.
AB  - Mycophenolate mofetil (MMF) was introduced as a new immune-suppression drug in
      the mid-1990s. It is widely utilized in solid-organ transplantation immune
      suppression regimens. Side effects include gastrointestinal (GI) toxicity in the
      form of nausea, vomiting, and diarrhea. Physicians tend to reduce the dose of MMF
      or switch their patients to an enterio-coated formula to overcome the side
      effects. Because GI side effects are well linked to MMF, colonoscopy is not
      utilized in most of the cases to investigate the diarrhea. However, Crohn's
      disease-like changes in the colon, erosive enterocolitis, and graft versus host
      disease-like colonic changes associated with the use of MMF have been reported.
      Colonic findings in five patients whose symptoms resolved after substituting
      another agent for MMF are described in the present report. Repeat colonoscopy 4
      months following discontinuation of MMF showed reparative changes in one of our
      patients. MMF is an important drug in organ transplantation immune-suppression
      regimens; however, with its widespread usage, additional side effects continue to
      be recognized.

PMID- 21094822
TI  - Correlation between SF-36 and six-minute walk distance in liver donors.
AB  - OBJECTIVE: We employed the 36-item short-form health survey (SF-36) and 6-minute
      walk distance (6MWD) to assess the quality of life (QoL) of donors after living
      donor liver transplantation (LDLT). METHODS: This longitudinal prospective study
      had data collection via an interview and test or a mailed survey. Fifty-one liver
      LDLT donors underwent testing before and after donation using the SF-36
      questionnaire and 6MWD. RESULTS: The physical component summary (PCS) of the SF
      36 declined (P < .0001) and the mental component summary (MCS) increased
      significantly (P = .04) at 1 month after donation. The 6MWD declined
      significantly at 2 weeks after donation (P < .0001). After standardization, there
      was a high correlation between PCS and 6MWD (r(2) = 0.766). CONCLUSIONS: Liver
      donation had a moderate impact on donor physical status, but enhanced mental
      status. Similar decreasing trends were observed in 6MWD and PCS. After donation,
      real physical performance predicted PCS but not MCS.

PMID- 21094823
TI  - Standard formula for liver volume in Middle Eastern Arabic adults.
AB  - OBJECTIVES: To determine a formula for estimating the standard liver volume (SLV)
      in Middle Eastern Arabic adults and to compare it with the 12 standard liver
      volume (SLV) formulas reported for eastern and western populations. METHODS:
      Liver volume measured using computed tomography (CTLV) was determined in 351
      Saudi Arabian adults older than 16 years without liver or body build abnormality.
      This measurement was correlated with body indices including age, sex, height,
      weight, body mass index, and body surface area to derive a new formula using
      multiple-step linear regression analysis. The CTLV was compared with the 12 SLV
      formulas using the t test, with error % as (SLV - CTLV)/CTLV * 100. RESULTS: Body
      weight was the only significant factor that correlated with CTLV, that is, 12.26
      * body weight (kg) + 555.65 (R(2) = .37; P = .000). Only the Vauthey formula
      (1267.28 * body surface area (m(2)) - 794.41) yielded an estimation of SLV that
      did not differ significantly from CTLV (P = .26), and had the least mean % error
      of +1% (underestimation by 15.7 mL) and the closest agreement, that is, 62.4%
      demonstrated less than +/-16% error). Other formulas also yielded acceptable
      agreement with mean % error less than 12%, although the differences from actual
      measurements were statistically significant. The Chengdu and Chouker formulas
      were the exceptions, with more than 16% underestimation or overestimation.
      CONCLUSIONS: Either the formulas derived in the present study and the Vauthey
      formula could be used to estimate SLV in Middle East Arabic adults. However, the
      moderate coefficient of determination (R(2) = .37) suggested wide interindividual
      variation. Caution must be exercised when using these formulas in preoperative
      planning.

PMID- 21094824
TI  - The effect of Prometheus device on laboratory markers of inflammation and tissue
      regeneration in acute liver failure management.
AB  - Prometheus, based on modified fractionated plasma separation and adsorption
      (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver
      transplantation. As the therapeutic effect of Prometheus is caused not only by
      the elimination of terminal metabolites, the aim of the study was to identify the
      effect of FPSA on the levels of cytokines and markers of inflammation and liver
      regeneration. Previous studies assessing cytokine levels involved mostly acute-on
      chronic liver failure patients. Data concerning markers of inflammation and liver
      regeneration are not published yet. Eleven patients (three males, eight females)
      with acute liver failure were investigated. These patients underwent 37
      therapeutic sessions on Prometheus device. Before and after each treatment, the
      plasma levels of selected cytokines, tumor necrosis factor alpha (TNFalpha), C
      reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and
      alpha(1) fetoprotein, were measured, and the kinetics of their plasma
      concentrations was evaluated. Before the therapy, elevated levels of interleukin
      (IL)-6, IL-8, IL-10, TNFalpha, CRP, and PCT were detected. The level of TNFalpha,
      CRP, PCT, and alpha(1) fetoprotein decreased significantly during the therapy. In
      contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10
      concentrations was not significant. Our results show that Prometheus is highly
      effective in clearing inflammatory mediators responsible for systemic
      inflammatory response syndrome and affects the serum levels of inflammatory and
      regeneration markers important for management of acute liver failure.

PMID- 21094825
TI  - Intraoperative changes in hyponatremia as a risk factor for prolonged mechanical
      ventilation after living donor liver transplantation.
AB  - Prolonged mechanical ventilation (PMV), a common clinical manifestation, may
      result in fatal outcomes after living donor liver transplantation (LDLT).
      Although hyponatremia contributes to neurologic alterations in association with
      PMV, the effects of acute changes in hyponatremia during LDLT have not been well
      studied. We sought to determine whether an acute change in hyponatremia during
      surgery might be a risk factor for PMV after LDLT. Perioperative data were
      retrospectively collected from 381 patients who underwent LDLT from January 2000
      to December 2008. PMV was defined as the need for >=24 hours of mechanical
      ventilation within the first postoperative week. Using multivariate logistic
      regression a simple comparison of perioperative variables between the PMV group
      and the non-PMV group yielded a predictive model to establish PMV. Thirty-seven
      patients (9.7%) experienced PMV after LDLT. Intraoperative changes in blood
      sodium were associated with postoperative PMV; however, the relationship was
      limited to patients with preoperative hyponatremia. Patients with PMV showed
      lower survival rates than those without PMV (56.3% vs 86.3%; P <.001). A
      multivariate analysis revealed that preoperative hepatic encephalopathy,
      hypotension during surgery (more than 3 bowls), and intraoperative changes in
      hyponatremia were predictive of PMV. Among the hyponatremia change subgroups,
      only a severe intraoperative change (>=10 mEq/L) was associated with PMV
      occurrence (odds ratio, 5.85; 95% confidence interval, 1.62 to 21.20, P = .007).
      In conclusion, a severe intraoperative change in hyponatremia was a risk factor
      for PMV in the immediate period after LDLT.

PMID- 21094826
TI  - Factors influencing the concentration of cytokines during liver transplantation.
AB  - Not only does the underlying disease that requires surgery constitute a
      significant stress to the human body, but also the surgery itself serves as a
      stressor. Cytokine secretion is activated in response to the surgical stress
      during liver transplantation. We examined 44 patients to compare cytokine levels,
      according to the underlying diseases causing liver failure (viral hepatitis vs
      alcoholic hepatitis), examining whether the values differed according to the
      model for end-stage liver disease (MELD) score [high (>=20) vs low (<20)]. Pro
      inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)1beta,
      and IL-6 and anti-inflammatory cytokines IL-4 and IL-10 were quantified using
      sandwich enzyme- linked immunoassays at three times: (1) after inducing
      anesthesia, (2) 60 minutes after the start of the anhepatic period, and (3) 60
      minutes after reperfusion. No difference in the level of any cytokine measured in
      our study was detected at any time point between the viral and the alcoholic
      hepatitis groups. Among the high MELD group, IL-1beta and IL-4 contents were
      higher than in the low MELD group at all time points (P < .05). IL-10
      concentrations at time 1 and TNF-alpha at time 2 were higher among the high MELD
      group (P < .05). In conclusion, the severity of the inflammatory and stress
      reactions expressed as cytokine concentrations did not differ according to the
      underlying liver disease, but did associate with the MELD score.

PMID- 21094827
TI  - Does model for end-stage liver disease score predict the short-term outcome of
      living donor liver transplantation?
AB  - OBJECTIVE: The objective of this study was to evaluate the predictive ability of
      the Model for End-Stage Liver Disease (MELD) score for short-term outcomes after
      living donor liver transplantation (LDLT). PATIENTS AND METHODS: The 135
      consecutive patients who underwent LDLT did not include prisoners or their
      organs. Patients were divided into a low (group A; MELD score <15), a moderate
      (group B; MELD score >=15 but <25), and a high MELD score (group C; MELD score
      >=25) group according to their preoperative score. We retrospectively analyzed
      the data concerning complications, biochemical parameters, and survival over 90
      postoperative days. RESULTS: Complications were similar among patients with a
      low, moderate, or high MELD score. The 90-day survival rates of group A, B, and C
      were 88%, 90%, and 90%, respectively (P = .960). Compared with groups A and B,
      group C showed a longer mean intensive care unit (ICU) stay. CONCLUSION:
      Preoperative MELD score may not help to predict short-term outcomes of LDLT.
      However, a high MELD score may be related to a prolonged ICU stay.

PMID- 21094828
TI  - Evolving strategies to prevent biliary strictures after living donor liver
      transplantation.
AB  - INTRODUCTION: The optimal surgical technique has not been elucidated that reduces
      the occurrence of biliary strictures after living donor liver transplantation
      (LDLT). METHOD: We performed retrospective analysis of 193 consecutive LDLTs,
      including 78 right and 115 left lobe grafts. An external biliary stent was used
      for all of the cases. RESULTS: The overall 1-, 3-, and 5-year biliary stricture
      free survival rates were 87.5%, 85.3%, and 85.3%, respectively. The 1- and 3-year
      biliary stricture-free survival rates for duct-to-duct reconstruction were 86.9%
      and 84.9%, and those for hepaticojejunostomy were 90.1% and 80.8%, respectively.
      A multivariate analysis revealed that the original number of graft bile ducts
      greater than the number of external stents, right lobe grafts, bile leaks, and
      recipient age older than 60 years represented the significant risk factors (P <
      .05) to develop a biliary stricture after LDLT. All cases with biliary strictures
      (n = 61) were initially managed nonsurgically, but 4 patients ultimately required
      interventions. CONCLUSIONS: Biliary reconstruction in LDLT using an appropriate
      number of external stents resulted in fairly acceptable outcomes. However, not
      only the proper use of stents or graft selection, but also nonsurgical factors,
      are important factors that determine the incidence of biliary strictures after
      LDLT.

PMID- 21094829
TI  - Does arterialisation time influence biliary tract complications after orthotopic
      liver transplantation?
AB  - BACKGROUND: In the cardiac death donor era, many reports deal with biliary tract
      complications and concerns about ischemic reperfusion injury owing to the
      exclusive arterial vascularization of the biliary tree, the warm ischemia time
      has been implicated as responsible for biliary lesions during organ procurement.
      We defined the arterialization time as the second warm ischemia time. Our purpose
      was to study the correlation between the arterialization time during liver
      implantation and the appearance of biliary lesions. METHODS: We retrospectively
      collected data from the last 5-years of orthotopic liver transplantation: namely,
      indications, cold perfusion fluid, cold ischemia time, operative procedure times,
      and acute rejection events. We excluded split-liver transplantations,
      retransplantations, pediatric patients, transplantations for cholestatic disease,
      cases where hepatic artery thrombosis happened before biliary complications, or
      patients with posttransplant cytomegalovirus infection. We defined 2 groups: A)
      without biliary complications; and B) with biliary complications. We compared the
      mean arterialization time using Student t test to define whether the warm
      ischemic time during implantation was responsible for biliary tract
      complications. A P value of <.05 was considered to be significant. RESULTS:
      Between 2004 and the end of 2008, we grafted 402 patients among whom 243 met the
      inclusion criteria: 198 in group A and 45 in group B. Only the cold ischemia time
      was significantly different between the 2 groups (P = .039). CONCLUSION: After
      the anhepatic time, the surgeon may take time for the arterial anastomosis
      without fearing increased biliary damage.

PMID- 21094830
TI  - Strong impact of acute kidney injury on survival after liver transplantation.
AB  - Acute kidney injury (AKI) is a major complication in orthotopic liver
      transplantation (OLT). In an evaluation of Acute Kidney Injury Network (AKIN)
      criteria in liver transplanted patients, we retrospectively analyzed the
      usefulness of these criteria to predict survival of 193 consecutive patients at a
      single center who underwent primary OLT for clinical parameters and peak AKI.
      Postoperative AKI according to AKIN occurred in 60.1% of the patients, namely,
      stages 1, 2, and 3 in 30%, 13% and 17.1% respectively. Using multivariate
      logistic regression, AKIN stage 1 and 2 AKI were independently associated with
      the pre-OLT Model for End-Stage Liver Disease (MELD) score and age, while stage 3
      AKI was independently associated with MELD and Acute Physiology and Chronic
      Health Evaluation (APACHE) II scores. The 28-day and 1-year mortality post-OLT of
      AKI patients were 15.5% and 25.9% respectively compared with 0% and 3.9% among
      non-AKI patients (P < .05 for both). The survival rates of non-AKI and stages 1,
      2, and 3 AKI subjects were 96%, 85.5%, 84%, and 45.3%, respectively. Cox
      regression analysis showed independent risk factors for mortality during the
      first year after transplantation to include post-OLT AKI (12.1; P < .05), post
      OLT infection (HR 4.7; P < .01), pre-OLT hypertension (HR 4.4; P < .01) hazard
      ratio [HR] and post-OLT APACHE II >=10 (HR 3.6; P < .05). We concluded that AKI
      as defined by the AKIN criteria is a major complication of OLT linked to a poor
      outcomes. It remains to be evaluated whether aggressive perioperative therapy to
      prevent AKI can improve survival among OLT patients.

PMID- 21094831
TI  - The value of tubular enzymes for early detection of acute kidney injury after
      liver transplantation: an observational study.
AB  - Tubular enzymes (TE) are early markers of acute kidney injury (AKI), but their
      value for liver transplant (LT) recipients is unknown. We sought to evaluate the
      usefulness of TE to predict AKI after LT. We enrolled Thirty-nine adult patients
      without AKI who had been admitted to the Intensive Care Unit (ICU). AKI was
      diagnosed according to the Acute Kidney Injury Network criteria. Of these
      patients, 23 had received orthotopic LT and 16 controls had been admitted for
      other conditions. Urinary lactate dehydrogenase (LDH), alkaline phosphatase (AF)
      and gamma-glutamyl transpeptidase (gamma-GT) measured on days 1 and 3 of the ICU
      stay were normalized to urinary creatinine concentrations. AKI was diagnosed in
      14 patients: 8 in the LT group and 6 in the control group. In the LT group, on
      the first day of the patients' stay in the ICU, urinary LDH (P = .032), AF (P =
      .022), and gamma-GT (P = .002) were significantly higher among those who
      developed AKI; these elevations preceded those of serum creatinine. In forward
      receiver-operating characteristic (ROC) plot analysis, the areas under the ROC
      curves were 0.8, 0.86, and 0.92 for LDH, AF, and gamma-GT, respectively. We
      concluded that TE determined early after LT are a helpful predictors of AKI.

PMID- 21094832
TI  - Chronic kidney disease following liver transplantation: a South Australian
      experience.
AB  - The incidence of chronic kidney disease (CKD) and its impact on survival have not
      been widely studied in the Australian liver transplant (OLT) population. The aims
      of this study were to evaluate the prevalence of CKD stages at various time
      points, calculate the cumulative incidence of progression to severe CKD, and
      study the impact of CKD stages on patient survival and risk factors for severe
      CKD in a single-center post-OLT population. We studied retrospectively 130
      patients who underwent OLT in South Australia with a minimum of 6 months of
      follow-up from 1992 to 2008. CKD was staged according to Kidney Diseases Outcome
      Quality Initiative Guidelines. Glomerular filtration rate (GFR) was calculated
      using the Modification of Diet in Renal Disease equation. Multiple pre- and post
      OLT variables were examined for their association with severe CKD. Log-rank tests
      and Cox regression analysis were performed to evaluate the survival data. The
      cumulative incidences of severe CKD (stages 4 and 5) at 2, 5, and 15 years were
      3.8%, 12.7%, and 14.8%, respectively. Severe CKD was associated with an increased
      mortality (hazard ratio 6.5; 95% confidence interval = 2.5-17.0; P < .001). Mild
      and moderate CKD stages were not associated with increased mortality. Risk
      factors for severe CKD were: female gender, hepatitis C infection, pre-OLT
      diabetes, acute renal failure post-OLT, and low 1-year GFR. Mild and moderate CKD
      are common post-OLT. The development of severe CKD, which can be predicted early
      in the post-OLT period, is strongly associated with an increased mortality rate.

PMID- 21094833
TI  - Factors associated with sustained virological response in liver transplant
      recipients with recurrent hepatitis C.
AB  - BACKGROUND: Antiviral therapy has achieved sustained virological response (SVR)
      in less than one third of orthotopic liver transplantation (OLT) patients with
      recurrent hepatitis C. AIM: The aim of this study was to identify predictors of
      SVR in OLT patients treated with pegylated interferon and ribavirin (PEG+RBV) for
      recurrent hepatitis C virus (HCV). METHODS: We analyzed data from our
      transplantation database for 62 subjects treated with PEG+RBV between August 2001
      and September 2008. After univariate examination for factors known to be
      associated with SVR, significant associations (P < .05) were probed using
      multivariate logistic regression. Kaplan-Meier patient and graft survival
      analyses were compared between patients with (n = 19; 30.6%) versus without SVR.
      RESULTS: On univariate analysis, longer duration of therapy, low pretreatment HCV
      RNA (<1 million IU/mL), and early virological response (EVR) were associated with
      SVR. On multivariate analysis, only low pretreatment HCV RNA predicted SVR.
      Patient survival was significantly higher in the SVR group. CONCLUSIONS:
      Covariates associated with SVR among OLT patients with recurrent HCV were similar
      to the pretransplantation group. Potentially modifiable risk factors, such as
      obesity, diabetes mellitus, and metabolic syndrome, were not significant
      predictors of treatment response. Patient survival was associated with SVR,
      highlighting the impact of successful HCV therapy on long-term post-OLT outcomes.

PMID- 21094834
TI  - Delayed kidney allograft function after simultaneous pancreas-kidney
      transplantation.
AB  - BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is one of the
      treatments for insulin-dependent chronic renal failure patients. METHODS: One
      year patient and kidney allograft survival rates of 150 patients undergoing SPKT
      were subjected to Cox regression and Kaplan-Meier analyses. Uni- and multivariate
      methods identified risk factors involved in allograft and patient survival.
      RESULTS: One-year patient and kidney allograft survival rates were 82% and 80%,
      respectively. Delayed graft function (DGF) (P = .001; hazard ratio [HR]5.41) and
      acute kidney rejection episodes (P = .016; HR 3.36) were related to 1 year
      patient survival as well as intra-abdominal infection (IAI) rates. (IAI). One
      year kidney allograft survival was related to DGF (P = .013; odds ratio [OR]
      3.39), acute rejection (P = .001; OR 4.74), and IAI (P = .003, OR 6.29). DGF was
      related to a time on dialysis >27 months (P = .046; OR 2.59), cold kidney
      ischemia time >14 hours (P = .027; OR 2.94), donor age >25 years (P = .03; OR
      2.82), and donor serum sodium concentration >155 mEq/L (P < .0001; OR 1.09).
      Female kidney to male recipient in 17% of the cases did not increase the risk of
      DGF. We observed an important correlation between donor serum sodium and
      creatinine (P < .0001), which suggested undertreatment of diabetes insipidus
      secondary to brain death. CONCLUSIONS: DGF, acute rejection, and IAI were the
      main determinants of survival after SPKT. Improving the care of deceased donors
      may reduce DGF occurrence.

PMID- 21094835
TI  - Intestinal obstruction due to internal hernia following pancreas transplantation.
AB  - BACKGROUND: Simultaneous pancreas-kidney transplantation has evolved as the best
      treatment for type 1 diabetic patients at end-stage renal disease. The surgical
      complication rate is high, which is an important barrier to the success of this
      procedure. The frequent complications that require relaparotomies include
      fistulas, graft thromboses, and intra-abdominal abscesses. Intestinal
      obstructions after pancreas transplantation due to internal herniation are not
      common. PURPOSE: The objective of this article was to review the literature about
      this problem and describe our personal experience in pancreas transplantation.
      METHODS: We examined the cases of small bowel obstruction secondary to an
      internal hernia after following 292 pancreas transplantations in our center from
      2000 to 2009 as well as performed a Medline literature review. RESULTS: Only 2
      articles described the diagnosis and treatment of internal hernias after pancreas
      transplantation. However, both contribution were from the same center reporting
      the same 3 cases, with surgical versus radiologic perspectives. We have described
      our 2 cases of young pancreas-kidney transplant patients who presented with acute
      intestinal obstruction due to internal hernia. CONCLUSION: Although internal
      hernias are rare, they are potentially fatal and difficult to diagnose when they
      occur after pancreas transplantation. Detection with early surgery demands a high
      degree of clinical vigilance.

PMID- 21094836
TI  - Pancreatic islet derived stem cells can express co-stimulatory molecules of
      antigen-presenting cells.
AB  - BACKGROUND: Antigen-presenting cells (APCs) are crucial intermediates in the
      generation of both innate and specific immune responses. It has long been
      understood that some APCs are resident in islets in situ as well as after
      isolation. Our aim was to investigate the presence of molecules involved in
      antigen presentation in rat pancreatic islet-derived stem cells (PI-SCs).
      METHODS: We used immunocytochemistry and reverse transcription polymerization
      chain reaction to study immunophenotypic characteristics; pluripotent-related
      gene expressions; transcripts coding for antigen-presenting surface proteins
      CD40, CD80, CD86; and major histocompatibility complex class II in addition to
      genes with known antiapoptotic functions including mitogen-activated protein
      kinase-activated protein kinase 2 (MAPKAPK2), tumor necrosis factor alpha-induced
      protein 3 (TNFAIP3) interacting protein 1 (TNIP1) and BCL3 of the PI-SCs.
      RESULTS: Rat PI-SCs were negative for CD45 as demonstrated by flow cytometry and
      for CD31, CD34, and CD71 as demonstrated by immunocytochemistry. Therefore, there
      was no evidence of hematopoietic precursors in the cultures. OCT4, SOX2, and REX1
      were expressed by rat PI-SCs. We determined the expression of genes for antigen
      presenting surface proteins CD40 and CD80, and genes with known antiapoptotic
      functions including MAPKAPK2, TNIP1 and BCL3, besides the surface protein, CD80,
      by flow cytometry. CONCLUSION: Expression of these genes by rat PI-SCs implied
      that they could be involved in the regulation of immunity in islets, highlighting
      the influence of protective role-playing antiapoptotic mechanisms on pancreatic
      islet cells. This study offers the potential to understand the molecular
      mechanisms of a devastating disease, type-1 diabetes mellitus.

PMID- 21094837
TI  - Reversible cardiomyopathies--a review.
AB  - End-stage renal disease, cirrhosis, obesity, tachycardia, and extreme stress have
      all been shown to result in impaired left ventricular function. It is becoming
      clear, however, that the cardiomyopathies associated with these states are
      reversible after resolution of the underlying process. In this article, we
      present the current data demonstrating that renal transplantation, liver
      transplantation, and bariatric surgery can lead to reversal of uremic, cirrhotic,
      and obesity cardiomyopathies, respectively. We also discuss the reversibility of
      tachycardia-induced cardiomyopathy after radiofrequency ablation or pharmacologic
      therapy for rate or rhythm control and the reversibility of stress-induced
      cardiomyopathy with supportive care.

PMID- 21094838
TI  - Antithymocyte globulin induction therapy in heart transplantation: prospective
      randomized study of high vs standard dosage.
AB  - BACKGROUND: In cardiac transplantation, high-dose antithymocyte globulin (ATG)
      induction therapy as short-term rejection prophylaxis has not been used.
      OBJECTIVE: To evaluate the efficacy and safety of intraoperative use of single
      high-dose ATG induction therapy after heart transplantation. PATIENTS AND
      METHODS: Fourteen patients received single high-dose ATG therapy plus shortened
      standard therapy (group1), and 16 patients received ATG standard therapy
      (group2). RESULTS: No perioperative deaths were reported. During follow-up, 3
      deaths were recorded. Five-year patient survival was 92.8% in groupl vs 85.7% in
      group2 (P = .34). The mean (SD) number of acute rejection episodes per patient
      was 2.5 (2.2) in the high-dose ATG group vs 2.7 (2.5) in the standard therapy
      group (P = .83), with 5-year freedom from acute rejection of 45.5% in group 1 vs
      35.6% in group 2 (P = .85). Infections were observed in 6 patients in group1 and
      in 8 patients in group2 (P = .69). Malignant disease was diagnosed in 1 patient
      in the high-dose group and 3 patients in the standard therapy group (P = .35).
      Chronic allograft vasculopathy was recognized in 4 patients (28%) in group1 and 8
      (50%) in group2 (P = .05). Five-year actuarial freedom from allograft
      vasculopathy was 69.2% in the high-dose ATG group vs 50.0%% in the standard
      therapy group (P = .35). CONCLUSIONS: High-dose ATG for prevention of rejection
      episodes is safe and efficacious, with a lower rate of early and late
      complications, in particular, graft vasculopathy.

PMID- 21094839
TI  - Domino heart transplantation: long-term outcome of recipients and their living
      donors: single center experience.
AB  - BACKGROUND: "Domino" cardiac procedure is an effective option to increase the
      donor pool when heart-lung transplantation (HLT) is the only treatment for
      patients with terminal cardiopneumopathy. We reviewed the long-term outcomes of
      domino cardiac donors and recipients at our institution. METHODS: Ten of 35
      patients who underwent HLT from 1991 onward served as domino cardiac donors. They
      included eight female and two male subjects of overall mean age of 33 years and
      mean weight of 55 kg. Their diagnoses were primary pulmonary hypertension (n = 6)
      as well as cystic fibrosis, bronchiectasis, Eisenmenger's syndrome, and
      bronchiolitis obliterans (n = 1 each). The domino cardiac recipients included six
      males and four females of overall mean age of 47 years and mean weight of 61 kg.
      They were affected by ischemic heart disease (n = 5), cardiomyopathy (n = 4), and
      valvular heart disease (n = 1). Mean pulmonary vascular resistance was 3 Wood
      units. The heart was used either in the orthotopic (n = 8) or in the heterotopic
      position (n = 2). RESULTS: The 1-, 5-, and 10-year survivals for the domino
      cardiac donors versus their recipients were 60%, 40%, 30% versus 90%, 70%, 60%,
      respectively. Five domino donors developed bronchiolitis obliterans syndrome.
      Among the domino recipients group, cardiac allograft vasculopathy was rare (n =
      1). Common causes of late death were in the domino recipients infections in the
      domino donors (n = 2) and malignancies. CONCLUSIONS: Our experience suggested
      good long-term results of the domino procedure.

PMID- 21094841
TI  - Common occurrence of everolimus-associated aphthous stomatitis in Japanese heart
      transplant recipients.
AB  - Mammalian target of rapamycin (mTOR) inhibitors display antiproliferative effects
      with less nephrotoxicity than calcineurin inhibitors. However, clinical use of
      mTOR inhibitors can be associated with a series of adverse events. We experienced
      cases of aphthous stomatitis associated with everolimus (EVL) in four Japanese
      heart transplant recipients treated at the target trough EVL blood level after a
      switch from mycophenolate mofetil between April and December 2007. All four
      patients developed aphthous stomatitis; three required reduction of the exposure
      and one, EVL discontinuation due to stomatitis as well as other side effects. All
      patients recovered from stomatitis after reduction or withdrawal of EVL. Thus, we
      considered that EVL-related stomatitis might occur commonly among the Japanese
      population. The proper dosage, effects, and frequency of the side effects of mTOR
      inhibitors may vary by ethnic population.

PMID- 21094840
TI  - Malignancies after heart transplantation: incidence, risk factors, and effects of
      calcineurin inhibitor withdrawal.
AB  - The objectives of the present study were to evaluate the incidence of
      malignancies and to describe the effects of immunosuppression on survival and
      recurrence of malignancies after heart transplantation (HTX). Data were analyzed
      in 211 cardiac allograft recipients, in whom HTX was performed between 1989 and
      2005. All of these patients survived for more than 2 years after HTX and received
      induction therapy with antithymocyte globulin (RATG) guided by T-cell monitoring
      since 1994. An immunosuppressive regimen consisting of cyclosporine A (CsA)
      combined with azathioprine was followed by CsA and mycophenolate mofetil (MMF) in
      2001; mammalian target of rapamycin (mTOR) inhibitors (everolimus/sirolimus) were
      used since 2003. Mean patient age at HTX was 51.4 +/- 10.5 years; mean follow-up
      time after HTX 9.2 +/- 4.7 years. Overall incidence of neoplasias was 30.8%.
      Individual risk factors associated with a higher risk of malignancy after HTX
      were higher age at transplantation (P = .003), male gender (P = .005) and
      ischemic cardiomyopathy before HTX (P = .04). Administration of azathioprine (P <
      .0001) or a calcineurin inhibitor (CNI) (P = .02) for more than 1 year was
      associated with development of malignancy, whereas significantly fewer
      malignancies were noticed in patients receiving an mTOR-inhibitor (P < .0001).
      Kaplan-Meier analysis demonstrated a strong statistical trend toward an improved
      survival in patients with a noncutaneous neoplasia switched to a CNI-free
      protocol (P = .05). This study demonstrated the impact of a variety of individual
      risk factors and immunosuppressive drugs on development of malignancy after HTX.
      Markedly fewer patients with noncutaneous malignancies died after switch to a CNI
      free regimen, not quite reaching statistical significance by Kaplan-Meier
      analysis, however.

PMID- 21094842
TI  - Serum midkine is related to NYHA class and cystatin C in heart transplant
      recipients.
AB  - Heart transplantation is now the established method of therapy for end-stage
      heart failure, with significantly improved outcomes over recent years. However,
      an increasingly prevalent complication in this population is that chronic kidney
      disease appears to be generally associated with subclinical inflammation. Midkine
      is a heparin-binding growth factor with various functions ranging from cell
      growth and survival to angiogenesis, repair, and inflammation. Recently, serum
      midkine has been reported to be a novel marker of cardiac events in heart failure
      patients. The aim of this study was to assess midkine concentration in 134 heart
      transplant recipients in relation to kidney function and New York Heart
      Association (NYHA) class. Heart transplant recipients had significantly higher
      serum creatinine, urea, cholesterol, triglycerides, fasting glucose, white blood
      cell count, and serum midkine, and lower estimated glomerular filtration rate
      than the control group. Serum midkine levels rose together with advancing NYHA
      class. Serum midkine was related to kidney function, NT-proBNP, transferrin, and
      prednisone dose. Cystatin C and NT-proBNP class turn out to be predictors of
      midkine in heart transplant recipients. Midkine levels are dependent on heart and
      kidney function, and might also represent a surrogate marker of subclinical
      inflammation.

PMID- 21094843
TI  - Preoperative evaluation improves the outcome in heart transplant recipients with
      pulmonary hypertension--retrospective analysis of 106 cases.
AB  - OBJECTIVES: The objectives of this study were to retrospectively analyze the
      value of preoperative evaluation and to analyze the risk factors of long-term
      mechanical ventilation in heart transplant recipients. METHODS: We analyzed the
      data of 106 patients prepared to receive heart transplants. Before the operation,
      according to the pulmonary vascular resistance (PVR) and transpulmonary gradient
      (TPG), the patients were divided into 2 groups: a pulmonary hypertension (PH)
      group and a pulmonary artery pressure normal (N) group. The vasodilator
      conditioning test as a predictive factor was performed in the PH group.
      Univariate analysis and logistic regression were used to examine the relationship
      between risk factors and long-term mechanical ventilation. The 30-day and long
      term survival rates were followed. RESULTS: PVR and TPG significantly decreased
      among the PH group after intravenous infusion epoprostenol and inhalation (nitric
      oxide). After preoperative evaluation, 96 patients underwent heart
      transplantation. There were no short-term deaths related to PH. There was no
      significant difference in mortality between the PH group and the N group. PH,
      hypotension after cardiopulmonary bypass, renal dysfunction, donor heart ischemia
      time, and ejection fraction <25% were risk factors for long-term mechanical
      ventilation. PH was not related to long-term deaths. CONCLUSION: A vasodilator
      conditioning test was reliable for PH patients undergoing heart transplantation
      for preoperative evaluation and preparation.

PMID- 21094844
TI  - Lung transplantation in cystic fibrosis patients in the Czech Republic: initial
      single-center experience.
AB  - BACKGROUND: Lung transplantation is a well established treatment for advanced
      lung diseases. METHODS: We compared the clinical results of patients with cystic
      fibrosis (CF) entered into the waiting list with those of patients after lung
      transplantation. RESULTS: Among 36 patients with CF on the waiting list, 23
      underwent lung transplantation, 8 died, 3 are still on the waiting list, and 2
      were excluded from the waiting list. The median waiting list time of 0.48 years
      (range, 0.03-2.37) was insignificantly longer for patients who died compared with
      transplanted patients (0.97 vs 0.44 years). Mortality of waiting-list patients
      was 25.8%. The median survival of transplant patients of 7.48 years (range 0.00
      10.85 years) was significantly lower among patients who were colonized (BCC)
      versus those who were not Burkholderia cepacia complex (0.19 vs 7.48 years; P =
      .041). The 1-, 3-, and 5-year patient survivals after lung transplantation were
      72.9, 54.4, and 54.4, respectively. CONCLUSION: The results of patients with
      cystic fibrosis on the waiting list versus after lung transplantation in our
      center were similar to those reported in the literature. We confirmed a less
      favorable prognosis of BCC-colonized patients.

PMID- 21094845
TI  - Hepatic artery resistance index at doppler ultrasonography is a useful parameter
      of hepatic graft-vs-host disease after allogeneic stem cell transplantation.
AB  - The hepatic artery resistance index (HARI) reflects portal venous blood pressure
      and resistance in several diseases of the liver. This study investigated whether
      preconditioning HARI values would predict hepatic complications such as hepatic
      graft-vs-host disease (GvHD), veno-occlusive disease, and drug- and sepsis
      related hepatotoxicity after allogeneic stem cell transplantation (SCT). Fifty
      nine patients who underwent allogeneic SCT were studied to determine whether pre
      SCT HARI would predict post-SCT hepatic complications. Twenty-six patients
      (44.1%) had high HARI values (>=0.74) before allogeneic SCT. At univariate
      analysis, a high HARI value correlated with incidence of hepatic GvHD.
      Multivariate analysis revealed that a nonmyeloablative regimen (P = .009; hazard
      ratio [HR], 4.05), infused CD34-positive cell dosage (P = .01; HR, 3.32), and
      high HARI (P = .02; HR, 2.82) were independent predictors. However, a high HARI
      did not correlate with nonrelapsed mortality and overall survival. In conclusion,
      it seems that a high HARI before SCT might be an important predictor of
      significant hepatic GvHD in patients after allogeneic SCT.

PMID- 21094846
TI  - Feasibility of second hematopoietic stem cell transplantation using reduced
      intensity conditioning with fludarabine and melphalan after a failed autologous
      hematopoietic stem cell transplantation.
AB  - This study was performed to determine the feasibility of second hematopoietic
      stem cell transplantation (HSCT) using reduced-intensity conditioning (RIC) with
      fludarabine and melphalan in patients with relapsed hematologic malignancies
      after a prior autologous HSCT. Twelve patients (multiple myeloma [n = 7], non
      Hodgkin lymphoma [n = 3], and acute myeloid leukemia [n = 2] received allogeneic
      HSCT using RIC with fludarabine (25 mg/m(2) for 5 days) and melphalan (140
      mg/m(2) for 1 day) after a failed autologous HSCT. The graft-versus-host disease
      (GVHD) prophylaxis consisted of cyclosporine plus a minidose of methotrexate. All
      patients achieved a neutrophil and platelet engraftment in a median 13.5 days and
      17.5 days, respectively. The transplant-related mortality was 2 patients (16.7%).
      Grade II-IV acute GVHD and chronic extensive GVHD were noted in 4 (33.3%) and 1
      patient (11.1%), respectively. Over a median follow-up duration of 376 days, 5
      patients were alive without evidence of disease. The estimated nonrelapse
      mortality at 1 year was 28.4%. The estimated overall survival rate at 1 year was
      58.3%, and the estimated event-free survival rate at 1 year was 41.7%. Allogeneic
      HSCT using RIC with fludarabine and melphalan appears to be feasible for a second
      HSCT in patients with relapsed hematologic malignancies after a failed autologous
      HSCT.

PMID- 21094847
TI  - Hematuria due to adenoviral infection in bone marrow transplant recipients.
AB  - Late-onset hemorrhagic cystitis (HC) caused by adenovirus (AdV) infection is a
      common complication in hematopoietic stem cell transplantation (HSCT) recipients.
      However, limited information exists regarding adenovirus-associated HC. We report
      a retrospective study of 84 hematopoietic stem cell transplant recipients that
      evaluated the incidence and risk factors for AdV-induced HC. The development of
      HC was strongly related to adenoviral infection (P = .004). Among 13 patients who
      developed late-onset HC, AdVs were identified as a causative agent in 10 cases.
      AdV preferentially affected younger (P = .013) and male patients. Affected
      subjects had been transplanted for either malignant (7/10) or nonmalignant
      disorders (3/10). Most cases of AdV-hematuria were self-limited single or
      recurrent mild hemorrhagic episodes (P = .000), occurring at a median of 41 days
      after transplantation and lasting an average of 4 days. Viral load in patients
      with AdV-induced HC was similar to infected subjects who did not develop HC (2.5
      * 10(3) vs 3.4 * 10(3) copies/mL). We HC occurring before 200 days was associated
      with a greater risk of a fatal outcome (P = .002) but occurrence of AdV infection
      did not affect a patient's survival. Our study confirmed the suggestion that non
      AdV coinfections may worsen the course of AdV-HC.

PMID- 21094848
TI  - Assessment of bioequivalence of a generic cyclosporine (Equoral) by a prospective
      randomized controlled trial on allogeneic stem cell transplant recipients.
AB  - INTRODUCTION: Bioequivalence of Equoral has been suggested by measurements of
      pharmacokinetic parameters in healthy volunteers and in stable renal transplant
      recipients, but not study in allogeneic stem cell transplant (ASCT) recipients.
      The aim of our study was to compare the pharmacokinetics and safety of Equoral to
      Neoral solution among ASCT recipients. PATIENTS AND METHODS: Our open-label, two
      way crossover, randomized controlled trial compared Equoral versus Neoral
      solutions in ASCT recipients. The 30 enrolled patients from June 2007 to November
      2008 had a 7 to 14-day duration of the test period. A 10-point blood sampling
      from 0 to 12 hours measured Cmax (extent of absorption), tmax (rate of
      absorption) and AUC(0-12h) (area under the concentration-time curve) calculated
      by the linear trapezoid rule. The study protocol was approved by the ethics
      committee. RESULTS: Median age was 26 years (range = 6-47). The mean
      pharmacokinetic features were: AUC(0-12h): Equoral 4162 +/- 1231 ng.mL/h vs
      Neoral 4370 +/- 1059 ng.mL/h (P = .50); Cmax: Equoral 821 +/- 244 ng/mL vs Neoral
      834 +/- 298 ng/mL (P = .86); and tmax: 105 minutes for both formulations.
      Comparable toxicities and rates of graft-versus-host disease were recorded in
      both groups. CONCLUSION: We suggest that Equoral and Neoral solution can be
      considered interchangeable in ASCT recipients.

PMID- 21094849
TI  - Human umbilical cord blood-derived stromal cells: a new resource in hematopoietic
      reconstitution in mouse haploidentical transplantation.
AB  - OBJECTIVE: Our previous study showed that human umbilical cord blood-derived
      stromal cells (hUcBdSCs) expanded CD34(+) cells in vitro. This study further
      explored the role of hUcBdSCs in vivo. METHODS: The cultured hUcBdSCs were
      infused into transplanted haploidentical mice to observe hematopoietic recovery
      and complications. RESULTS: The engraftment was faster in transplantation with
      hUcBdSCs than without hUcBdSCs. The numbers of fibroblast (CFU-F),
      granulocyte/monocyte (CFU-GM), erythrocytic (CFU-E), and megakaryocyte (CFU-Mg)
      colony-forming units were greater among mice transplanted with hUcBdSCs than
      without hUcBdSCs. The scoring of graft-versus-host disease was significantly
      lower in mice that had been subjected to transplantation with hUcBdSCs than
      without hUcBdSCs. The infused hUcBdSCs migrated to the bone marrow of the
      recipients. CONCLUSIONS: These data indicated that hUcBdSCs improved
      hematopoietic reconstitution in haploidentical transplantation in mice.

PMID- 21094850
TI  - Adult endothelial progenitor cells retain hematopoiesis potential.
AB  - Hematopoietic stem cells (HSCs) are derived from endothelium in the aortic-gonado
      mesonephric (AGM) region during embryogenesis. But little is known about whether
      endothelial progenitor cells (EPCs) retain hematopoiesis potential after birth.
      In this study, we isolated adult EPCs from the bone marrow of C57BL/6 mice and
      identified them with an endothelial functional assay and by the CD31(+) CD133(+)
      CD45(-/dim) VEGFR2(+) phenotype. EPCs isolated from green fluorescence protein
      (GFP) transgenic C57BL/6 mice were cotransfused with bone marrow cells from wild
      type C57BL/6 mice into lethally irradiated BABL/c mice. One month after
      transplantation, granulocytes (25.73 +/- 5.43%) and lymphocytes (12.68 +/- 3.26%)
      in peripheral blood showed GFP(+), referred to as donor EPC-derived blood cells.
      After an additional month, the percentage of GFP(+) granulocytes decreased to
      (3.69 +/- 1.43%), whereas the percentage of GFP(+) lymphocytes showed no
      significant difference. Most of the GFP(+) elements showed a diffuse distribution
      in the spleen; but some were present as aggregates forming lymphoid nodules.
      GFP(+) endothelial cells were observed in the liver sinusoids, intestinal villi,
      and lung of recipient mice. These results indicated that adult EPCs not only took
      part in vasculogenesis, but also retained hematopoietic ability.

PMID- 21094851
TI  - Transplanted fingerprints: a preliminary case report 40 months posttransplant.
AB  - For the past century, fingerprints have been considered permanent and specific
      for each individual. However, with the advances in transplantology, fingerprints
      have lost their permanence. Because no study has yet been described, we examined
      possible changes in the fingerprint pattern of a transplanted hand. In 2006, we
      performed a hand transplantation on a 32-year-old man. The donor was revealed to
      have had a criminal record; his fingerprints were stored in the Polish automated
      fingerprint identification system. A forensic technician fingerprinted the
      transplanted hand nine times between June 2006 and September 2009. The appearance
      of minutiae and white lines and the change in the distance between papillary
      ridges were assessed in the thumbprints of the transplanted hand. The appearance
      of white lines was only temporary; at no point did they impair fingerprint
      identification. No significant changes occurred in the distance between the
      friction ridges. The observed small differences were ascribed to the two
      techniques used to collect the prints (spoon vs rolling). The number of minutiae
      ranged from 1 to 3, reaching a maximum in the third posttransplant month. A 40
      month observation showed no significant changes in the fingerprints of the
      transplanted hand. Nevertheless, a long-term study is needed because of the risk
      of chronic rejection. The noninvasiveness of dactylography argues for inspecting
      its application to diagnose acute rejection. Finally, lawmakers should be made
      aware of the personal-protection issues related to the growing number of hand
      transplant recipients.

PMID- 21094852
TI  - Immune suppression produced by intrathymic inoculation with xenogeneic antigen
      and whole-body gamma-irradiation in a pig-to-monkey heart transplantation model.
AB  - OBJECTIVE: To validate the use of pig-to-monkey transplantation as an
      experimental animal model for study of the induction of immune suppression of
      cardiac xenografts via intrathymic inoculation with xenogeneic spleen cells and
      whole-body gamma-irradiation. MATERIALS AND METHODS: Donors (Meishan pigs) and
      recipients (Rhesus monkeys) were randomized into 3 groups. Group 2 was the
      control group; group 2 received whole-body irradiation, and group 3 received
      whole-body irradiation and intrathymic inoculation. In each group, survival time
      of heterotopic heart xenografts in monkeys were observed. A mixed lymphocyte
      reaction assay with (3)H thymidine was used to examine changes in lymphocyte
      function in all groups on the day of transplantation. In each group, recipient
      serum was harvested for analysis of IL-2 and IL-10 concentrations. RESULTS: Mean
      (SD) survival time of donor hearts in group 3 was significantly longer (91.1
      [22.8] hours) than in group 1 (36.6 [5.8] hours) (P < .01). The results of mixed
      lymphocyte reaction assay demonstrated a significant reduction in the stimulation
      index in group 3 compared with groups 1 and 2 (P < .01) when recipient
      splenocytes responded to the donor stimulator. The IL-2 concentration in
      recipients in all groups was much higher during rejection of xenografts than
      before transplantation (P < .01). CONCLUSION: These results suggest that
      pretreatment with intrathymic inoculation or whole-body irradiation induces T
      cell immunosuppression. The IL-2 concentration is closely correlated with
      xenograft rejection.

PMID- 21094853
TI  - In vitro Ad5F35-mediated CTLA4-Ig gene transfer prolongs pig skin xenotransplant
      survival.
AB  - Wound closure and coverage are the biggest challenges faced by medical
      practitioners in treating severe burns. Fresh cadaver allografts are still
      considered to be the gold standard skin substitute. Unfortunately, their use is
      severely impeded by inadequate availability. In this report we endeavored to
      solve this problem by using gene-modified pig skin as a substitute for human
      skin. We report that adenovirus (Ad)-mediated transfer of human cytotoxic T
      lymphocyte-associated antigen 4 immunoglobin (CTLA4-Ig) into pig skin in vitro is
      a useful approach to lower immunostimulatory ability and improve the take of pig
      skin for wound coverage. To optimize gene transfer efficiency, we also compared
      exogenous gene transfer efficiency in pig skin by Ad5F35 vector with that of the
      widely used Ad5. The uptake efficiency of Ad5F35 was about 1.3 times more than
      that of Ad5, and the survival time on rat burn wounds was prolonged by about 3
      days. Our results demonstrate that CTLA4Ig gene-modified pig skin is a promising
      biologic dressing for wound coverage and Ad5F35 an effective viral carrier for
      delivery.

PMID- 21094855
TI  - Human hepatoma HepaRG cell line engraftment in severe combined immunodeficient *
      beige mice using mouse-specific anti-Fas antibody.
AB  - Chimeric mice with repopulated human hepatocytes are widely used for drug
      development research. HepaRG cell line is a naturally immortalized human liver
      cell line with progenitor properties and inducible bipotent differentiation
      capability. It would be useful if HepaRG cells could repopulate damaged livers
      severe, combined immunodeficient * beige (SCID/bg) mice and exhibit special human
      hepatic features. After inducing mouse hepatocyte apoptosis with an antimouse
      agonistic Fas monoclonal antibody (Jo2 mAb), HepaRG cells with bipotent
      differentiation capability were repopulated in SCID/bg mouse livers. HepaRG cells
      were transplanted intrasplenically into SCID/bg mice treated with 0.2 mg/kg Jo2
      mAb once a week for 10 weeks. Human hepatocyte repopulation was characterized by
      immunohistochemistry for human serum albumin (HSA), Hep Par1, and CK18 and by
      immunofluorescence staining for HSA. Human albumin mRNA was detected by reverse
      transcription polymerase chain reactions. HSA levels were quantified by Western
      blotting and enzyme-linked immunosorbent assays. Our results showed that HepaRG
      cell engraftment protected mice from the effects of Jo2 mAb-mediated liver
      hemorrhage and hepatocyte apoptosis. At 2 weeks after transplantation, increase
      concentrations of HSA were detected in recipient blood and liver. At 12 weeks
      after transplantation, approximately 15%-20% of mice showed livers repopulated
      with human hepatocytes. In conclusion, normal SCID/bg mice were suitable
      recipients for HepaRG cell transplantation when induced with Jo2 mAb. This
      chimeric mouse model with HepaRG cells could serve as a useful model for in vivo
      studies of drug metabolism and hepatitis virus infections.

PMID- 21094856
TI  - Effects and mechanisms of tacrolimus on development of murine Th17 cells.
AB  - Tacrolimus (Tac, FK506) is a widely used T-cell-targeted immunosuppression drug
      known as a calcineurin inhibitor. However, its pharmacologic effects on T-helper
      type 17 (Th17) cells have not been fully elucidated. Herein, we demonstrate that
      Tac inhibits Th17 cell differentiation and proliferation, and expression of IL-17
      messenger RNA. The proposed mechanism is that Tac inhibits calcineurin and T-cell
      receptor stimulation-induced cell division. Because Th17 cells participate in
      allograft rejection, the results of the present study suggest a novel model of
      immunosuppression effects of Tac. In addition, they provide further implications
      for the therapeutic immunosuppression effects of Tac on allograft rejection.

PMID- 21094854
TI  - Effects of bone marrow stromal cells and umbilical cord blood-derived stromal
      cells on daunorubicin-resistant residual Jurkat cells.
AB  - OBJECTIVE: To observe the effects of the hematopoietic inductive microenvironment
      (HIM) simulated by stromal cells of different origins on daunorubicin-resistant
      residual Jurkat cells (Jurkat/DNR cells). METHODS: Jurkat/DNR cells were cultured
      and identified. Human umbilical cord blood-derived stromal cells (UCBDSCs) and
      normal human bone marrow stromal cells (BMSCs) were isolated and cocultured with
      Jurkat/DNR cells. Jurkat/DNR cells were collected after 14 days of coculture and
      analyzed with regard to cell proliferation and differentiation abilities,
      apoptosis, drug sensitivity, and MRD1 multidrug resistance gene mRNA expression.
      RESULTS: UCBDSC-simulated HIM suppressed proliferation and promoted apoptosis,
      differentiation, and drug sensitivity of Jurkat/DNR cells more significantly than
      BMSC-simulated HIM. CONCLUSIONS: Both BMSCs and UCBDSCs reconstruct the leukemic
      HIM and reverse drug resistance in Jurkat/DNR cells. UCBDSCs reconstruct the
      leukemic HIM and reverse drug resistance more significantly than BMSCs.

PMID- 21094857
TI  - Kupffer cells promote acute rejection via induction of Th17 differentiation in
      rat liver allografts.
AB  - BACKGROUND: Th17, a newly identified CD4+ T-cell subset, has been implicated in
      transplant rejection. Differentiation of Th17 cells is associated with
      transforming growth factor-beta (TGF-beta) and interleukin-6 (IL-6), which are
      the main products of Kupffer cells. OBJECTIVE: To determine whether Kupffer cells
      promote acute liver allograft rejection by inducing Th17 cell differentiation.
      METHODS: A rat model of allogeneic liver transplantation using Dark Agouti (DA)
      to Brown Norway (BN) rats was established with or without gadolinium chloride
      (GdCl(3)) pretreatment. Isogeneic liver transplantation (BN to BN) was performed
      as a control. Concentrations of cytokines secreted by Kupffer cells or Th17
      related cytokines detected in the liver and peripheral blood were analyzed using
      immunohistochemistry assays, flow cytometry, and enzyme-linked immunosorbent
      assays. Survival differences were compared between treatment groups. In vitro,
      Kupffer cells from liver grafts were isolated and co-cultured with naive CD4 T
      cells. RESULTS: Both Kupffer cells and Th17 cells infiltrated liver allografts,
      accompanied by an increase in concentrations of IL-6 and TGF-beta. Pretreatment
      with GdCl(3) attenuated intragraft infiltration of Kupffer cells and Th17 cells,
      and decreased IL-6 and TGF-beta concentrations. Liver function improved after
      pretreatment, and mean (SD) survival time was prolonged, compared with the
      control group (16.33 [0.96] days vs 11.50 [0.99] days, respectively; P < .01). In
      vitro, Kupffer cells from livers with allografts secreted significantly higher
      concentrations of IL-6 and TGF-beta and induced Th17 differentiation more
      effectively compared with livers with isografts (30.8% vs 8.1%, respectively).
      CONCLUSION: Kupffer cells have the potential to induce Th17 cells by secreting IL
      6 and TGF-beta, and as a result, promote acute liver allograft rejection.

PMID- 21094858
TI  - Astragalus membranaceus injection delayed allograft survival related with CD4+
      CD25+ regulatory T cells.
AB  - INTRODUCTION: Recently it has been reported that Astragalus membranaceus
      injection (AMI) inhibits immune responses, but whether it affects alloimmunity is
      not clear. It has been shown that the CD4(+) CD25(+) regulatory T cells (Treg)
      down-regulate immune responses. The aim of our study was to investigate the
      effects of AMI on allograft survival and its relation to Treg. MATERIALS AND
      METHODS: Allografted mice were administered AMI for 14 consecutive days with
      observations of graft survival. The specific recall response, the ratio of Treg,
      the expression of Foxp3 mRNA, and interleukin (IL)-10 secretion were measured by
      mixed lymphocyte reactions (MLR), FCM, reverse transcriptase-polymerase chain
      reaction, and radioimmunoassay, respectively. RESULTS: AMI significantly
      prolonged allograft survival by up-regulating the Treg ratio and promoting Foxp3
      expression (P < .05). The ratio of Tregs, the expression of Foxp3 mRNA, and the
      IL-10 level in the AMI administration group increased from day 7, to reach a
      maximum at day 14, recovering to the initial level on day 21. No obvious
      difference was detected between the AMI and a cyclosporine group. CONCLUSION: AMI
      administered in vivo prolonged allograft survival associated with promotion of
      Treg activities.

PMID- 21094859
TI  - Astilbin suppresses acute heart allograft rejection by inhibiting maturation and
      function of dendritic cells in mice.
AB  - The effect of astilbin on acute graft rejection was investigated in C57BL/6 mice
      carrying BALB/c hearts heterotopically transplanted into the neck vessels. Daily
      treatment with astilbin (50, 125, or 250 mg/kg intraperitoneally) significantly
      prolonged the survival of grafts in a dose-dependent manner, when cyclosporine
      (CsA; 5 mg/kg) was co-administered with astilbin (250 mg/kg), there was more
      potent immunosuppression than that solely achieved by 20 mg/kg CsA. Addition of
      10 mg/mL astilbin significantly inhibited the proliferation and activation of T
      cells, as determined by (3)H-thymidine deoxyribose uptake, Western blots for
      nuclear factor kappaB and p38, and 1-way mixed lymphocyte reactions (MLR). Mature
      and antigen-presenting functions of dendritic cells (DCs) also were inhibited by
      astilbin (10 mg/mL), as determined by morphologic observations, flow cytometry,
      and MLR. These observations suggested that astilbin is a potential candidate for
      immunosuppressive therapy after heart engraftment. Inhibiting the maturation and
      antigen-presenting function of DCs and thus preventing T-cells activation is a
      possible mechanism underlying its inhibitory effects on acute heart allograft
      rejection.

PMID- 21094861
TI  - Effects of orthotopic liver transplantation in inbred rats on bone biomechanical
      properties.
AB  - AIM: To determine the effects of orthotopic liver transplantation in inbred rats
      on the mechanical properties of bones at different anatomic sites. METHODS: The
      24 rats that survived liver transplantation were paired with sham-operated rats
      of similar body weight. Six months after surgery, the lumbar vertebra, the
      proximal femur, and the middle femoral shaft were measured for their
      biomechanical properties and bone mineral density. RESULTS: The ultimate force,
      the ultimate stress, the Young modulus and the bone mineral density of both the
      proximal femur and the middle femur shaft of the rats were significantly reduced
      in the liver transplant group. However, no significant change was observed in the
      various parameters that indicate the biomechanical properties and the bone
      mineral density of the lumbar vertebra. CONCLUSIONS: Orthotopic liver
      transplantation impairs the biomechanical properties of the proximal femur and
      the middle femoral shaft. Orthotopic liver transplantation itself is one of the
      risk factors for posttransplant fracture.

PMID- 21094860
TI  - Antigen sampling on the Peyer's patches in a murine small bowel transplantation
      model.
AB  - AIM: This study investigated changes in the mucosal barrier of transplanted
      intestines with particular emphasis on antigen sampling by Peyer's patches (PPs).
      METHODS: Heterotopic small bowel transplantation (SBTx) was performed as
      described previously. C57BL/6 mice were used as donors and BALB/c (allogeneic) or
      C57BL/6 mice (syngeneic) as recipients. Tacrolimus (FK506) or saline control was
      administered to the recipients for 2 weeks. Four groups included in this study
      were: syngeneic with or without immunosuppression (SYN and SYN + FK506,
      respectively) and allogeneic with or without immunosuppression (ALLO and ALLO +
      FK506, respectively). Animals were sacrificed weekly after SBTx to evaluate
      microfold (M) cells within PPs and for routine histology. By the third
      postoperative week, recipients were subjected to an intestine loop model to
      examine the uptake of microbeads by M cells as well as expression of Toll-like
      receptor 2 (TLR2) protein in the PPs with or without a TLR2 agonist challenge. We
      also measured occludin expression on follicle-associated epithelium (FAE) of PPs
      in the grafts. RESULTS: Transportation of microbeads through the PPs of the
      grafts increased in the ALLO + FK506 group compared with that in the SYN or SYN +
      FK506 group. This finding was accompanied by increased expression of TLR2 in the
      PPs and a gradually increased number of M cells following SBTx. However, occludin
      expression patterns on the FAE of the PPs in the grafts were similar among SYN,
      SYN + FK506, and ALLO + FK506 groups. Nevertheless, as transportation of
      microbeads and TLR2 expression in the PPs of the grafts was enhanced once exposed
      to Pam3Cys-SKKKK, similar results were not seen in the ALLO + FK506 group.
      CONCLUSIONS: Our study revealed that the mucosal barrier of intestinal grafts is
      altered under alloreactivity as evidenced by enhanced antigen sampling. Such a
      change may provide a pathway for translocation of microorganisms in the lumen.

PMID- 21094862
TI  - Use of genetically modified allograft to deliver local immunomodulatory molecule
      with minimal systemic toxicity in a rat model of allogeneic skin flap
      transplantation.
AB  - The effects of OX40-OX40 ligand (OX40L) costimulatory pathway blockade to prevent
      T-cell-mediated acute rejection were investigated in a rat model of allogeneic
      superficial inferior epigastric artery flap transplantation. An ex vivo gene
      transfer technique was used to modify allografts to locally deliver an
      immunomodulatory molecule. The flaps were separated from donors, perfused with an
      adenoviral vector expressing the OX40 immunoglobulin (AdOX40Ig) for 1 hour, and
      incubated at 37 degrees C for 2 hours. Before transplantation, the flaps were
      flushed with phosphate-buffered saline solution to remove unincorporated viral
      particles. Recipients were randomly divided into 5 groups, and treated with
      topical OX40Ig gene transfer, a single low dose of rapamycin alone, or a
      combination of agents. Graft survival was assessed using histopathologic
      classification of skin rejection. All animals in the untreated group (n = 9) or
      the group treated with adenovirus expressing green fluorescence protein (n = 9)
      developed grade 3 clinical rejection by postoperative day 7. No significant
      difference was observed in graft survival between the locally treated AdOX40Ig
      groups (mean [SD], 8.1 [0.7] days) and the untreated groups (7.7 [1.2] days)
      could be observed (P > .05, t test). Graft survival in the locally treated
      AdOX40Ig groups was extended to 18.7 (1.2) days when transduction was combined
      with a low dose of rapamycin, a significant improvement over survival with
      rapamycin treatment alone (13.2 [0.6] days) (P < .01). These results demonstrated
      that local immunomodulation by the allograft itself and low-dose rapamycin
      treatment promote graft acceptance. This protocol may enable reduction of the
      dosage of immunosuppressive drugs needed for successful inhibition of acute
      rejection in the early postoperative period.

PMID- 21094863
TI  - Oxidant and antioxidant activity in rabbit livers treated with zoledronic acid.
AB  - Zoledronic acid (ZA), a nitrogen-bearing bisphosphonate, is used to treat the
      hypercalcemia associated with cancer. In addition to its antiumor effects, it
      acts as an osteoclast inhibitor. To investigate the effects of ZA on oxidative
      stress and antioxidants, we studied reduced glutathione (GSH) and antioxidant
      gamma glutamate cysteine, including nitrite and nitrate, which are endproducts of
      nitric oxide (NO) as well as malondialdehyde (MDA) in rabbit liver tissue. In the
      study ZA (100 MUg/kg) was administered to 7 rabbits that were fed ad libitum for
      comparison with untreated controls. MDA was studied using Thiobarbituric acid
      reactive substance reduction, NO using cadmium reduction, GSH using an enzymatic
      method yielding dithinitrobenzene yellow substance. We observed significantly
      higher MDA and NO levels in the ZA group (P < .0001), whereas GSH levels were
      significantly lower (P < .0001). Tissues were examined histopathologically.
      According to our results we find ZA induced rabbit liver oxidative stress and
      decreases with antioxidant levels in liver tissue. Further studies are needed to
      explore the safe use of this agent.

PMID- 21094864
TI  - Effects of different doses of statins on liver regeneration through angiogenesis
      and possible relation between these effects and acute phase responses.
AB  - BACKGROUND: We examined the effects of two doses of statins on liver regeneration
      through angiogenesis and its possible relation to acute phase responses.
      MATERIALS AND METHODS: Seventy-two rats were randomly divided into three groups:
      controls; low-dose atorvastatin (0.5 mg/kg/d); high-dose atorvastatin (2.5
      mg/kg/d). Statin was administered daily by oral gavage for 7 days. After
      atorvastatin treatment, all animals in the three groups underwent 70%
      hepatectomy. Thereafter animals were subdivided into three subgroups, to evaluate
      the characteristics of liver regeneration proliferating cell nuclear antigen
      (PCNA), angiogenesis (KDR/Flk-1 [vascular endothelial growth factor-2]) and acute
      phase response (serum interleukin [IL]-6) at 12, 24, and 72 hours. RESULTS: At
      the 24 hours posthepatectomy, low-dose compared with high-dose atorvastatin
      increased liver regeneration (P = .004) and angiogenic responses compared also to
      controls (P = .026 and P = .059). However, there appeared no difference in IL-6
      expression (P = .159). At the 72 hours posthepatectomy, low-dose atorvastatin
      treatment increased liver regeneration compared with controls (P = .047), but it
      showed no significant difference from the high-dose treatment (P = .109). Low
      doses of statin increased angiogenic responses compared with both control and
      high-dose animals (P = .016 and P = .002). Moreover, the high-dose group
      displayed decreased angiogenic responses compared with the control group (P =
      .044). Serum IL-6 expression was significantly greater among both low- and high
      dose groups compared with controls (P = .005 and P = .003, respectively).
      CONCLUSIONS: Low-dose statin treatment increased KDR/Flk-1-dependent
      angiogenesis, which resulted in an increased regeneration response. In contrast,
      high-dose statin therapy decreased angiogenesis without affecting long-term
      regeneration responses. Finally, statin therapy may contribute to liver
      regeneration due to prolonged IL-6 expression independent of statin doses.

PMID- 21094865
TI  - Heterotopic heart transplantation in rats: improved anesthetic and surgical
      technique.
AB  - OBJECTIVE: An updated anesthetic and surgical technique in a rat model of
      heterotopic heart transplantation is described. MATERIALS AND METHODS: A
      microsurgical technique via a suprarenal approach was performed, and is described
      in stepwise fashion, and several technical improvements are compared with
      previous descriptions. Lewis rats were used as donors and recipients (syngeneic
      model). RESULTS: Factors that affected early surgical outcome included type of
      anesthetic used; surgeon skill, experience in handling blood vessels, and
      knowledge of small-animal anatomy; gentle manipulation during the operation; and
      duration of surgery (<1 hour). Use of isoflurane inhalation anesthesia (10 rats)
      vs intraperitoneal injection of ketamine, 75 mg/kg, and dexmedetomidine, 0.25
      mg/kg (20 rats), was associated with improved early survival (90%) and no
      occurrence of paralysis, paraparesis, bleeding, or intestinal ischemia. Long-term
      survival (>11 months) with a functioning graft was achieved in all 9 surviving
      animals. CONCLUSIONS: Survival was substantially improved with administration of
      isoflurane anesthesia; surgeon microvascular surgical skills and knowledge of
      small-animal anatomy, and duration of surgery less than 1 hour. These factors
      collectively contributed to successful early outcomes after heterotopic heart
      transplantation in rats, with 90% freedom from morbidity and mortality, and
      resulted in long-term survival (>11 months) with a functioning graft in a
      syngeneic model. This heterotopic model in rats is suitable for short- and long
      term studies of heart transplantation.

PMID- 21094866
TI  - Administration of granulocyte colony-stimulating factor ameliorates radiation
      induced hepatic fibrosis in mice.
AB  - On the basis of the recent report that granulocyte colony-stimulating factor (G
      CSF) treatment significantly improves survival and liver histology among
      chemically injured mice, we investigated whether G-CSF administration could
      contribute to faster recovery and promote tissue repair after local liver
      irradiation. Bone marrow chimeric female C57BL/6 mice were treated with G-CSF at
      days 7, 14, and 21 after local liver irradiation. We assessed the fibrosis index
      and the origin of proliferating cells reconstituting the liver at 2 or 5 weeks
      after radiation challenge. At day 35 after local irradiation, we observed G-CSF
      treatment to significantly reduce radiation-induced liver damage and collagen
      deposition. In addition, hepatic hydroxyproline levels and serum fibrosis markers
      in mice receiving G-CSF administration after radiation challenge were
      significantly lower compared with those of control mice. More importantly,
      histological examination suggested that recovery from hepatic damage was much
      better among the G-CSF-treated mice. Immunofluorescence and fluorescence in situ
      hybridization analyses revealed that donor cells engrafted into the host liver
      displayed epithelium-like morphology and expressed albumin, albeit at low
      frequency. These results suggested that G-CSF treatment initiated endogenous
      hepatic tissue regeneration in response to radiation injury and ameliorated its
      fibrogenic effects.

PMID- 21094867
TI  - Liver transplantation for metastasized extragastrointestinal stromal tumor: a
      case report and an overview of literature.
AB  - A 63-year-old woman underwent living donor liver transplantation for hepatic
      metastases of an extragastrointestinal stromal tumor (EGIST) originating from the
      rectovaginal space. Due to a multifocal extrahepatic tumor recurrence, treatment
      with imatinib mesylate was started after extensive pharmacokinetic studies to
      rule out possible interactions with immunosuppressives. We performed several re-
      resections for EGIST recurrence thereafter. At the last follow-up, 17 years after
      primary tumor resection and 10 years after living donor liver transplantation,
      the patient is symptom-free under immunosuppressive and imatinib mesylate
      treatments with a 2-cm stable recurrent pararectal EGIST. To our knowledge, this
      is the only report published on a patient who underwent transplantation for
      hepatic EGIST metastases with a posttransplantation follow-up of 10 years and the
      first report on living donor liver transplantation for metastasized EGIST. This
      is the first description of pharmacokinetics of imatinib and its main active
      metabolite CGP74588 in a liver transplant recipient.

PMID- 21094869
TI  - De novo autoimmune hepatitis with centrilobular necrosis following liver
      transplantation for primary biliary cirrhosis: a case report.
AB  - De novo autoimmune hepatitis (AIH) occurred in patients who underwent liver
      transplantation for a different etiology. This 55-year-old woman was transplanted
      due to PBC. One year after liver transplantation, she complained of fatigue.
      Liver function tests showed markedly elevated serum alanine transaminase (ALT)
      and globulin levels. She also tested positive for anti-nuclear antibodies (ANA).
      Liver biopsy showed lymphocytic and plasmacytic infiltration in the portal and
      periportal areas, with numerous areas of bridging centrilobular necrosis,
      indicating AIH. She had a pretreatment AIH score of 16 points, and a
      posttreatment score of 18 points according to the scoring system of the
      International AIH Group (IAHG). The patient was treated effectively with
      prednisone, but then suffered two further episodes of AIH as a result of
      decreasing the prednisone dose. Histological features on liver biopsy were
      similar to those on initial presentation. Treatment with prednisone and
      azathioprine resulted in a dramatically improved outcome. Her liver function and
      globulin levels rapidly returned to normal and have remained so thereafter.

PMID- 21094868
TI  - Fatal sclerosing peritonitis associated with primary effusion lymphoma after
      liver transplantation: a case report.
AB  - Sclerosing peritonitis (SP) after liver transplantation has been described in 10
      cases in the literature. The etiology is still unknown; however, SP is considered
      a consequence of chronic irritation and inflammation. It can be classified as
      primary (idiopathic) or secondary form. Although pathologically benign, it has a
      negative course, resulting in unrelenting abdominal pain, small bowel
      obstruction, malnutrition, and death. Posttransplantation lymphoproliferative
      disease (PTLD) is one of the leading causes of late death. Its development is
      related to complex interactions between immunosuppressive drugs and environmental
      agents. Primary effusion lymphoma (PEL) as an onset presentation of PTLD is
      relatively uncommon. Most examples of effusion-based PTLD have been secondary to
      widespread solid organ involvement and associated with Human herpes virus 8 (HHV
      8) recurrence. Here in, we report a case of a 55-year-old man who rapidly
      developed refractory ascites and bacterial peritonitis at 1-year after orthotopic
      liver transplantation (OLT) with a fatal clinical course at the beginning of the
      second follow-up year after an uncomplicated liver transplantation due to
      cryptogenic cirrhosis. The diagnosis of HHV-8-positive lymphoma was established
      by postmortem examination with multiple solid localizations and massive dense
      fibrotic adhesions encompassing the small intestine, colon, liver, and porta
      hepatis without any involvement of body cavities.

PMID- 21094870
TI  - Living donor liver transplantation for Dorfman-Chanarin syndrome with 1 year
      follow-up: case report.
AB  - A 27-year-old Japanese man underwent liver transplantation because of
      uncompensated cirrhosis due to Dorfman-Chanarin syndrome (DCS). At birth, the
      patient displayed ichthyosis and liver dysfunction. Moreover, mental retardation
      appeared and intracytoplasmic vacuoles were observed within peripheral blood
      neutrophils. A fatty liver was also noticed, leading to the diagnosis of DCS.
      When he was referred to our hospital, his American Society of Anesthesiologists
      score was 3. The findings of computed tomography showed liver atrophy,
      splenomegaly, and ascites. The Child-Pugh score was B, and the Model for End
      stage Liver Disease score was 14. The pathophysiology was DCS with uncompensated
      liver cirrhosis. Therefore, living donor liver transplantation (LDLT) was
      performed from the patient's brother. The histological appearance of the resected
      liver revealed macrovesicular steatosis in most hepatocytes with excess fibrous
      tissue in the portal areas. These findings were compatible with nonalcoholic
      steatohepatitis. Although the patient's mental retardation and characteristic
      appearance have not improved, good liver function has been maintained since LDLT.
      An outpatient protocol liver biopsy performed at 12 months after LDLT did not
      show recurrence of macrovesicular steatosis.

PMID- 21094871
TI  - Posttransplant bilioportal fistula with portal vein thrombosis: a case report.
AB  - An 8-year-old female patient, known to have post-Kasai biliary atresia with mild
      intrapulmonary shunting, underwent living donor liver transplantation because of
      recurrent cholangitis. After the treatment of postoperative biliary stricture
      with percutaneous transhepatic biliary drainage, the patient subsequently
      developed hematochezia with portal vein thrombosis. The intraoperative findings
      showed portal vein thrombosis with a bilioportal fistula. We performed closure of
      the bilioportal fistula and reconstruction of the portal vein with a native
      internal jugular vein interposition graft. A bilioportal fistula due to
      percutaneous hepatobiliary procedures is a reportedly a rare complication
      following liver transplantation. The patient is currently doing well after a
      successful surgical intervention.

PMID- 21094872
TI  - Unusual presentation of left hepatic vein in deceased donor: case report.
AB  - An anomaly of the left hepatic vein was discovered in a deceased donor for whole
      liver transplantation. This vein was attached by a thin bridge of tissue to the
      suprahepatic inferior vena cava cuff, which received the right and middle hepatic
      vein in a common trunk. The left hepatic vein and the common trunk drained
      together into the right atrium. The thin bridge of tissue connecting the 2
      independent vessels was severed, and ex situ reduction of the left lateral
      segments was using a harmonic scalpel. Although a graft with reduced size is not
      ideal, ex situ reduction should be considered a valuable option when viability of
      the left lateral segments is uncertain in the donor or at the back table.

PMID- 21094873
TI  - Extracorporeal shock wave lithotripsy (ESWL) of a renal calculus in a liver
      transplant recipient: report of a severe complication--a case report.
AB  - INTRODUCTION: Extracorporeal shock wave lithotripsy (ESWL) has evolved as a
      standard treatment modality for calculi of the upper urinary tract. Noninvasive
      ESWL shows rare life-threatening complications. Herein we have reported the case
      of a liver transplant recipient who developed severe renal hemorrhage after ESWL
      of a renal calculus. Transfusion of erythrocytes and platelets led to
      anaphylactic shock with acute renal failure requiring intensive care. The patient
      fully recovered shortly thereafter and was discharged home with a residual left
      kidney stone measuring 8 mm. CASE PRESENTATION: A 55-year-old man with a single
      left kidney underwent ESWL due to symptomatic left nephrolithiasis. He had
      undergone successful liver transplantation 11 years earlier. At the time of ESWL
      his liver functions were normal and his serum creatinine level was 1.3 mg/dL. Two
      weeks before the treatment a double pigtail ureteral stent was inserted because
      of a symptomatic left hydronephrosis. Several hours after ESWL treatment the
      patient complained of left-sided flank pain. An ultrasound revealed a large
      subcapsular hematoma of the left kidney, which was confirmed using abdominal
      computed tomography (CT). With the patient being hemodynamically stable, we opted
      for conservative management. Despite postinterventional complications, the
      patient made a fast recovery. CONCLUSION: ESWL is a noninvasive, safe, and
      efficient method to treat renal calculi. Patients who are at risk for hemorrhage
      should undergo close postinterventional monitoring, including red blood cell
      count and renal ultrasound.

PMID- 21094874
TI  - Recurrent non-melanoma skin cancer: remission of field cancerization after
      conversion from calcineurin inhibitor- to proliferation signal inhibitor-based
      immunosuppression in a cardiac transplant recipient.
AB  - Non-melanoma skin cancers (NMSCs) are the most common malignancies after solid
      organ transplantation. Their incidence increases with time after transplantation.
      Calcineurin-inhibitors (CNIs) and azathioprine are known as skin neoplasia
      initiating and -enhancing immunosuppressants. In contrast, increasing clinical
      experience suggests a relevant antiproliferative effect of mammalian target of
      rapamycin inhibitors, also named proliferation signal inhibitors (PSIs). We
      report the case of a cardiac allograft recipient with an impressive and
      consolidated reduction of recurrent NMSC, observed after conversion from CNI
      therapy to a PSI-based protocol.

PMID- 21094875
TI  - Aerosolized tacrolimus: a case report in a lung transplant recipient.
AB  - Long-term outcomes after lung transplantation remain poor mainly to the
      development of bronchiolitis obliterans syndrome (BOS). Currently, treatment
      options for BOS are very limited. Strategies to prevent and treat this
      complication include the use of aerosolized therapy with only cyclosporine used
      in patients to date. We describe the use of aerosolized tacrolimus in a lung
      transplant recipient with BOS. The patient demonstrated clinical improvement in
      functional capacity and oxygenation while receiving tacrolimus by nebulization.
      Further research is needed to study whether aerosolized tacrolimus is beneficial
      in lung transplant recipients with BOS.

PMID- 21094876
TI  - Infliximab as therapeutic option in steroid-refractory ulcerative colitis after
      kidney transplantation: case report.
AB  - In inflammatory bowel disease refractory to established therapies, treatment with
      biological agents such as monoclonal tumor necrosis factor-alpha antibodies is an
      established therapeutic option. However, application in renal allograft
      recipients is either not licensed or has not yet been systematically examined.
      Herein, we present 2 case reports of renal allograft recipients who had steroid
      refractory ulcerative colitis who demonstrated improvement of symptoms after
      treatment with infliximab, without signs of effect on transplant function. In
      both patients, stool frequency decreased significantly. Colonoscopy controls and
      histologic examination after initiation of treatment revealed a state of
      remission. Renal function parameters and drug concentrations remained constant.

PMID- 21094877
TI  - A lucky fall? Case report.
AB  - Renal cell carcinomas (RCCs) account for 3% of all solid neoplasms, with an
      increased incidence after renal transplantation. In transplant recipients, RCCs
      predominantly occur in the patient's native kidneys. Herein is reported a case of
      a localized RCC of recipient origin that developed in the donor allograft and was
      detected 8 years after renal transplantation. Treatment with high-intensity
      focussed ultrasound followed by partial nephrectomy was successful, averting the
      need for dialysis therapy.

PMID- 21094879
TI  - Late-onset intestinal perforation in the setting of posttransplantation
      microangiopathy: a case report.
AB  - Intestinal perforation in the setting of posttransplantation microangiopathy
      (TMA) is a very rare event and might be considered a terminal event of intestinal
      microangiopathy (i-TMA), a rather rarely recognized posttransplantation
      complication, as it overlaps with the more common intestinal graft-versus-host
      disease (GVHD). Cases of i-TMA described in literature occurred within with first
      100 days posttransplantation or shortly thereafter. In this report, we describe a
      case of late-onset intestinal perforation that occurred in the setting of
      systemic microangiopathy more than a year after allogeneic transplantation. In
      our case, the patient poorly responded to treatment secondary to refractory
      mircoangiopathy.

PMID- 21094878
TI  - Simultaneous pancreas-kidney transplantation in HIV-infected patients: a case
      report and literature review.
AB  - Since the introduction of combined antiretroviral therapy (cART), solid organ
      transplantation (SOT) has become a therapeutic option for the HIV-positive
      population. In contrast with liver and kidney transplantation, only three
      simultaneous pancreas-kidney transplants (SPKT) have been reported among HIV
      infected patients. Herein we have reported the first SPKT in an HIV-infected
      patient in Spain. The pancreas graft failed at 2 weeks and the patient died at 9
      months because of a Pseudomonas aeruginosa infection. The three recipients
      reported in the literature lived, despite the failure of both the pancreas and
      kidney grafts in one subject. Despite the poor outcome of our case, HIV-1
      infection was controlled after transplantation (stable CD4(+) cells and no AIDS
      related events), and the kidney graft functioned with no episodes of rejection.
      The cART regimen used in the pretransplant period was switched at the time of
      transplantation to raltegravir and two nucleoside reverse transcriptase
      inhibitors (NRTI). Raltegravir has no interactions with immunosuppressive drugs.
      Target plasma levels of tacrolimus were achieved at a dose similar to that used
      in HIV-negative transplant recipients. The most adequate antiretroviral regimen
      for HIV-infected SOT recipients has not yet been established; however, one may
      consider switching protease inhibitors or non-NRTI-based regimens for a
      raltegravir-based regimen at the time of transplantation.

PMID- 21094880
TI  - Treatment of acute graft-vs-host disease after simultaneous pancreas-kidney
      transplantation: a case report.
AB  - Whereas neutropenia is common after solid-organ transplantation, graft-vs-host
      disease is unusual, especially after simultaneous pancreas-kidney
      transplantation. Most cases reported in the literature give few details of
      treatment approach, and all were fatal. A 45-year-old man with diabetes underwent
      simultaneous pancreas-kidney transplantation at our center, with organs from a
      female donor. Two weeks postoperatively, he was readmitted with fever, malaise,
      and neutropenia. A bone marrow biopsy specimen demonstrated that two-thirds of
      the lymphocytes were of female karyotype. Graft-vs-host disease was diagnosed.
      Aggressive immunosuppression therapy was administered; however, the patient died.
      To our knowledge, this is the first case report with specific details of a
      treatment protocol and sequential short tandem repeat data.

PMID- 21094881
TI  - Sex differences in the human brain, their underpinnings and implications.
      Preface.

PMID- 21094882
TI  - Sex differences in brain anatomy.
AB  - Over the past decades scientific studies have revealed a number of striking sex
      differences in the human brain. This chapter highlights some of the most
      important discoveries with particular emphasis on macro-anatomical observations
      based on magnetic resonance imaging (MRI) data. Cross-references to animal
      studies and to post mortem analyses, as well as an overview with respect to micro
      anatomical findings, are provided. The chapter concludes with a discussion of
      possible determinants of sex differences in brain anatomy. The main goal of this
      chapter is to exemplify the variety of findings and to demonstrate how the
      presence, magnitude, and direction of observed sex differences strongly depend on
      a number of factors including (but not limited to) the following: the brain
      structure examined (cerebral cortex, corpus callosum, etc.), the specific brain
      feature assessed (cortical thickness, cortical convolution, etc.), the degree of
      regional specificity (global gray matter volume, voxel-wise gray matter volume,
      etc.), and whether measurements are adjusted for individual brain size or not.

PMID- 21094883
TI  - Sex differences in the human brain: a developmental perspective.
AB  - At a population level, women and men differ in a wide variety of behavioral
      traits and in the probabilities of developing certain mental disorders. Some of
      these sex differences may be related to sexual dimorphism in brain structure, as
      it emerges during prenatal and post-natal development. Here, I provide a brief
      overview of the sex-chromosome-specific pathways that underlie sexual dimorphisms
      in general, describe the most common brain phenotypes derived in vivo with
      magnetic resonance imaging, discuss the challenges in interpreting these
      phenotypes vis-a-vis the underlying neurobiology, and, finally, review the known
      sex differences in brain structure from birth, through adolescence, to adulthood.

PMID- 21094884
TI  - Sex influences on brain and emotional memory: the burden of proof has shifted.
AB  - Sex influences are ubiquitous on brain function, including the human brain. This
      chapter addresses the issue of sex influences on human brain function first as it
      pertains to studies of emotional memory, then as it pertains to the field of
      neuroscience more generally. The striking quantity and diversity of sex-related
      influences on nervous system function argue that the burden of proof regarding
      the issue has shifted from those examining the issue in their investigations
      generally having to justify why, to those not doing so having to justify why not.

PMID- 21094885
TI  - Sexual differentiation of the human brain in relation to gender identity and
      sexual orientation.
AB  - It is believed that during the intrauterine period the fetal brain develops in
      the male direction through a direct action of testosterone on the developing
      nerve cells, or in the female direction through the absence of this hormone
      surge. According to this concept, our gender identity (the conviction of
      belonging to the male or female gender) and sexual orientation should be
      programmed into our brain structures when we are still in the womb. However,
      since sexual differentiation of the genitals takes place in the first two months
      of pregnancy and sexual differentiation of the brain starts in the second half of
      pregnancy, these two processes can be influenced independently, which may result
      in transsexuality. This also means that in the event of ambiguous sex at birth,
      the degree of masculinization of the genitals may not reflect the degree of
      masculinization of the brain. There is no proof that social environment after
      birth has an effect on gender identity or sexual orientation. Data on genetic and
      hormone independent influence on gender identity are presently divergent and do
      not provide convincing information about the underlying etiology. To what extent
      fetal programming may determine sexual orientation is also a matter of
      discussion. A number of studies show patterns of sex atypical cerebral dimorphism
      in homosexual subjects. Although the crucial question, namely how such complex
      functions as sexual orientation and identity are processed in the brain remains
      unanswered, emerging data point at a key role of specific neuronal circuits
      involving the hypothalamus.

PMID- 21094886
TI  - Genes and brain sex differences.
AB  - Throughout development, numerous biological events occur that differentially
      affect males and females. Specifically, sex-determining genes that are triggered
      by the sex-chromosome complement initiate a series of events that determine an
      organism's sex and lead to the differentiation of the body in sex-specific ways.
      Such events contribute to many unique sex differences, including the
      susceptibility to different diseases. Although it was believed that sex hormones
      singularly differentiated the brain and body, there is emerging research showing
      that genes also play a direct role. In this chapter, we review this line of work
      and focus on the use of a unique mouse model that separates the effect of gonadal
      hormones and sex chromosomes. As genetic technology continues to advance, our
      understanding of the role that hormones and genes play in sex differences can be
      used to advance the physical and mental health of both men and women.

PMID- 21094887
TI  - Genetic and epigenetic underpinnings of sex differences in the brain and in
      neurological and psychiatric disease susceptibility.
AB  - There are numerous examples of sex differences in brain and behavior and in
      susceptibility to a broad range of brain diseases. For example, gene expression
      is sexually dimorphic during brain development, adult life, and aging. These
      differences are orchestrated by the interplay between genetic, hormonal, and
      environmental influences. However, the molecular mechanisms that underpin these
      differences have not been fully elucidated. Because recent studies have
      highlighted the key roles played by epigenetic processes in regulating gene
      expression and mediating brain form and function, this chapter reviews emerging
      evidence that shows how epigenetic mechanisms including DNA methylation, histone
      modifications, and chromatin remodeling, and non-coding RNAs (ncRNAs) are
      responsible for promoting sexual dimorphism in the brain. Differential profiles
      of DNA methylation and histone modifications are found in dimorphic brain regions
      such as the hypothalamus as a result of sex hormone exposure during developmental
      critical periods. The elaboration of specific epigenetic marks is also linked
      with regulating sex hormone signaling pathways later in life. Furthermore, the
      expression and function of epigenetic factors such as the methyl-CpG-binding
      protein, MeCP2, and the histone-modifying enzymes, UTX and UTY, are sexually
      dimorphic in the brain. ncRNAs are also implicated in promoting sex differences.
      For example, X inactivation-specific transcript (XIST) is a long ncRNA that
      mediates X chromosome inactivation, a seminal developmental process that is
      particularly important in brain. These observations imply that understanding
      epigenetic mechanisms, which regulate dimorphic gene expression and function, is
      necessary for developing a more comprehensive view of sex differences in brain.
      These emerging findings also suggest that epigenetic mechanisms are, in part,
      responsible for the differential susceptibility between males and females that is
      characteristic of a spectrum of neurological and psychiatric disorders.

PMID- 21094888
TI  - Gene expression in neuroendocrine cells during the critical period for sexual
      differentiation of the brain.
AB  - Following transcription of the SRY gene on the Y chromosome of genetic males, a
      cascade of genomic and biochemical events causes the developing brain to be
      influenced by two testosterone metabolites, the potent androgen
      dihydrotestosterone and the aromatization product estradiol (E2). These steroid
      hormones binding to their cognate nuclear receptors produce differential gene
      expression profiles between male and female brains, and as a result, male-typical
      sex behaviors appear in adulthood and female-typical sex behaviors are
      suppressed. Although anatomical and cellular substrates underlying sexually
      dimorphic brain and behavior have been identified, still very little information
      is available about the molecular mechanisms involved. Microarray technology is a
      powerful technique that can be a used to assess the changes in thousands of gene
      transcripts simultaneously. Thus such high-throughput screening may be a useful
      initial step in the identification of estrogen-responsive genes involved in the
      sexual differentiation of brain.

PMID- 21094890
TI  - Sex and gender differences in pain and analgesia.
AB  - It is a clinical reality that women make up the large majority of chronic pain
      patients, and there is now consensus from laboratory experiments that when
      differences are seen, women are more sensitive to pain than men. Research in this
      field has now begun to concentrate on finding explanations for this sex
      difference. Although sex differences in sociocultural, psychological, and
      experiential factors likely play important roles, evidence largely from animal
      studies has revealed surprisingly robust and often qualitative sex differences at
      low levels of the neuraxis. Although not yet able to affect clinical practice,
      the continued study of sex differences in pain may have important implications
      for the development of new analgesic strategies.

PMID- 21094891
TI  - The skewed sex distribution in affective disorders--a diagnostic, social, or
      biological problem?

PMID- 21094892
TI  - Empathizing, systemizing, and the extreme male brain theory of autism.
AB  - Females in the general population on average have a stronger drive to empathize,
      and males in the general population on average have a stronger drive to
      systemize. Evidence related to these claims is reviewed. People with autism
      spectrum conditions have below average empathy alongside intact or even above
      average interest in systems. As such, they can be conceptualized as an extreme of
      the typical male brain.

PMID- 21094893
TI  - Gender and the injured brain.
AB  - Ischemic brain injury is increasingly recognized as progressing through non
      identical mechanisms in the male vs female brain. It is increasingly accepted
      that women are protected from cerebrovascular disease relative to men even beyond
      their menopausal years, and that young boys have higher stroke rates than do
      girls. The biological basis for this sexual dimorphism in epidemiology of
      ischemic brain injury, and less clearly in its outcome, is only partially known.
      However, both hormone-dependent and hormone-independent factors are likely
      involved, the latter of which is emphasized in this chapter. Understanding the
      molecular and cell-based mechanisms underlying sex differences in ischemic brain
      injury is an important step toward designing more effective therapeutic
      interventions and molecular targets in stroke.

PMID- 21094894
TI  - Incretins and insulin secretion. Preface.

PMID- 21094889
TI  - Neurosteroids: endogenous role in the human brain and therapeutic potentials.
AB  - This chapter provides an overview of neurosteroids, especially their impact on
      the brain, sex differences and their therapeutic potentials. Neurosteroids are
      synthesized within the brain and rapidly modulate neuronal excitability. They are
      classified as pregnane neurosteroids, such as allopregnanolone and
      allotetrahydrodeoxycorticosterone, androstane neurosteroids, such as
      androstanediol and etiocholanolone, and sulfated neurosteroids such as
      pregnenolone sulfate. Neurosteroids such as allopregnanolone are positive
      allosteric modulators of GABA-A receptors with powerful anti-seizure activity in
      diverse animal models. Neurosteroids increase both synaptic and tonic inhibition.
      They are endogenous regulators of seizure susceptibility, anxiety, and stress.
      Sulfated neurosteroids such as pregnenolone sulfate, which are negative GABA-A
      receptor modulators, are memory-enhancing agents. Sex differences in
      susceptibility to brain disorders could be due to neurosteroids and sexual
      dimorphism in specific structures of the human brain. Synthetic neurosteroids
      that exhibit better bioavailability and efficacy and drugs that enhance
      neurosteroid synthesis have therapeutic potential in anxiety, epilepsy, and other
      brain disorders. Clinical trials with the synthetic neurosteroid analog
      ganaxolone in the treatment of epilepsy have been encouraging. Neurosteroidogenic
      agents that lack benzodiazepine-like side effects show promise in the treatment
      of anxiety and depression.

PMID- 21094895
TI  - Evolution of genes for incretin hormones and their receptors.
AB  - The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) are essential components in the regulation of
      blood glucose levels in mammals. These two incretins are produced by
      evolutionarily related genes and these hormones show similarity in sequence as
      both are glucagon-like sequences. Genes for these hormones have been identified
      in a number of diverse vertebrate species indicating that they originated prior
      to the earliest divergences of vertebrate species. However, analysis of
      functional and sequence data suggest that each of these hormones acquired
      incretin activity independently, and only since the divergence of tetrapods from
      fish. Not only are the hormones related, but so are their receptors. Like the
      hormones, the incretin action of the receptors is not a product of a shared
      common ancestral history, as the receptors for GLP-1 and GIP are not most closely
      related. Further study of the physiological functions of GLP-1 and GIP in
      additional vertebrates is required to better understand the origin of incretin
      action.

PMID- 21094896
TI  - Pleiotropic actions of the incretin hormones.
AB  - The insulin secretory response to a meal results largely from glucose stimulation
      of the pancreatic islets and both direct and indirect (autonomic) glucose
      dependent stimulation by incretin hormones released from the gastrointestinal
      tract. Two incretins, Glucose-dependent insulinotropic polypeptide (GIP) and
      glucagon-like peptide-1 (GLP-1), have so far been identified. Localization of the
      cognate G protein-coupled receptors for GIP and GLP-1 revealed that they are
      present in numerous tissues in addition to the endocrine pancreas, including the
      gastrointestinal, cardiovascular, central nervous and autonomic nervous systems
      (ANSs), adipose tissue, and bone. At these sites, the incretin hormones exert a
      range of pleiotropic effects, many of which contribute to the integration of
      processes involved in the regulation of food intake, and nutrient and mineral
      processing and storage. From detailed studies at the cellular and molecular
      level, it is also evident that both incretin hormones act via multiple signal
      transduction pathways that regulate both acute and long-term cell function. Here,
      we provide an overview of current knowledge relating to the physiological roles
      of GIP and GLP-1, with specific emphasis on their modes of action on islet
      hormone secretion, beta-cell proliferation and survival, central and autonomic
      neuronal function, gastrointestinal motility, and glucose and lipid metabolism.
      However, it is emphasized that despite intensive research on the various body
      systems, in many cases there is uncertainty as to the pathways by which the
      incretins mediate their pleiotropic effects and only a rudimentary understanding
      of the underlying cellular mechanisms involved, and these are challenges for the
      future.

PMID- 21094897
TI  - Dietary effects on incretin hormone secretion.
AB  - The delivery of nutrients from the stomach into the duodenum and their subsequent
      interaction with the small intestine to stimulate incretin hormone release are
      central determinants of the glycemic response. The incretin effect has hitherto
      been attributed to the secretion of glucose-dependent insulinotropic polypeptide
      (GIP) and glucagon-like peptide-1 (GLP-1) from enteroendocrine cells in the
      intestinal epithelium. A number of recent studies have yielded fundamental
      insights into the influence of individual nutrients on incretin release and the
      mechanisms involved in the detection of carbohydrates, fats, and proteins by
      enteroendocrine cells, including the K(ATP) channel, sodium-glucose cotransporter
      1 (SGLT1), sweet taste receptors, G-protein-coupled receptors (GPRs), and
      oligopeptide transporter 1 (PepT1). Dietary modification, including modifying
      macronutrient composition or the consumption of "preloads" in advance of a meal,
      represents a novel approach to manipulate the incretin response and thereby
      regulate glucose homeostasis in patients with type 2 diabetes. This review
      focuses on the effects of individual nutrients on incretin hormone secretion, our
      current understanding of the signaling mechanisms that trigger secretion by
      enteroendocrine cells, and the therapeutic implications of these observations.

PMID- 21094898
TI  - K-cells and glucose-dependent insulinotropic polypeptide in health and disease.
AB  - In the 1970s, glucose-dependent insulinotropic polypeptide (GIP, formerly gastric
      inhibitory polypeptide), a 42-amino acid peptide hormone, was discovered through
      a search for enterogastrones and subsequently identified as an incretin, or an
      insulinotropic hormone secreted in response to intraluminal nutrients.
      Independent of the discovery of GIP, the K-cell was identified in small intestine
      by characteristic ultrastructural features. Subsequently, it was realized that K
      cells are the predominant source of circulating GIP. The density of K-cells may
      increase under conditions including high-fat diet and obesity, and generally
      correlates with plasma GIP levels. In addition to GIP, K-cells secrete xenin, a
      peptide with as of yet poorly understood physiological functions, and GIP is
      often colocalized with the other incretin hormone glucagon-like peptide-1 (GLP
      1). Differential posttranslational processing of proGIP produces 30 and 42 amino
      acid versions of GIP. Its secretion is elicited by intraluminal nutrients,
      especially carbohydrate and fat, through the action of SGLT1, GPR40, GPR120, and
      GPR119. There is also evidence of regulation of GIP secretion via neural pathways
      and somatostatin. Intracellular signaling mechanisms of GIP secretion are still
      elusive but include activation of adenylyl cyclase, protein kinase A (PKA), and
      protein kinase C (PKC). GIP has extrapancreatic actions on adipogenesis, neural
      progenitor cell proliferation, and bone metabolism. However, the clinical or
      physiological relevance of these extrapancreatic actions remain to be defined in
      humans. The application of GIP as a glucose-lowering drug is limited due to
      reduced efficacy in humans with type 2 diabetes and its potential obesogenic
      effects demonstrated by rodent studies. There is some evidence to suggest that a
      reduction in GIP production or action may be a strategy to reduce obesity. The
      meal-dependent nature of GIP release makes K-cells a potential target for
      genetically engineered production of satiety factors or glucose-lowering agents,
      for example, insulin. Transgenic mice engineered to produce insulin from
      intestinal K-cells are resistant to diabetes induced by a beta-cell toxin.
      Collectively, K-cells and GIP play important roles in health and disease, and
      both may be targets for novel therapies.

PMID- 21094899
TI  - The emerging role of promiscuous 7TM receptors as chemosensors for food intake.
AB  - In recent years, several highly promiscuous seven transmembrane (7TM) receptors
      have been cloned and characterized of which many are activated broadly by amino
      acids, proteolytic degradation products, carbohydrates, or free fatty acids
      (FFAs) and are expressed in taste tissue, the gastrointestinal (GI) tract,
      endocrine glands, adipose tissue, and/or kidney. This has led to the hypothesis
      that these receptors may act as sensors of food intake modulating, for example,
      release of incretin hormones from the gut, insulin/glucagon from the pancreas,
      and leptin from adipose tissue. In the present review, we describe the molecular
      mechanisms of nutrient-sensing of the calcium-sensing receptor (CaR), the G
      protein-coupled receptor family C, group 6, subtype A (GPRC6A), and the taste1
      receptor T1R1/T1R3-sensing L-alpha-amino acids; the carbohydrate-sensing
      T1R2/T1R3 receptor; the proteolytic degradation product sensor GPR93 (also termed
      GPR92); and the FFA sensing receptors FFA1, FFA2, FFA3, GPR84, and GPR120. Due to
      their omnipresent nature, the natural ligands have had limited usability in
      pharmacological/physiological studies which has hampered the elucidation of the
      physiological function and therapeutic prospect of their receptors. However, an
      increasing number of subtype-selective ligands and/or receptor knockout mice are
      being developed which at least for some of the receptors have validated them as
      promising drug targets in, for example, type II diabetes.

PMID- 21094900
TI  - Central regulation of glucose-dependent insulinotropic polypeptide secretion.
AB  - Glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP
      1) are potent stimulators of glucose-dependent insulin secretion, a phenomenon
      known as incretin effect. After food ingestion, the circulating levels of GIP and
      GLP-1 rise more quickly than could be explained by the arrival of unabsorbed
      nutrients that have a direct stimulatory effect on K- and L-cells. Previous
      studies have thoroughly investigated the possible role of the autonomic nervous
      system on GIP secretion, demonstrating conflicting results. Recent data from
      intracerebroventricular infusions of different neuropeptides that participate in
      the overall regulation of energy homeostasis, suggest the possible existence of
      additional neuroendocrine mechanisms that may contribute to a central regulation
      of GIP secretion.

PMID- 21094901
TI  - Incretin hormone secretion over the day.
AB  - The two incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and
      glucagon-like peptide-1 (GLP-1) are key factors in the regulation of islet
      function and glucose metabolism, and incretin-based therapy for type 2 diabetes
      has gained considerable interest during recent years. Regulation of incretin
      hormone secretion is less well characterized. The main stimulus for incretin
      hormone secretion is presence of nutrients in the intestinal lumen, and
      carbohydrate, fat as well as protein all have the capacity to stimulate GIP and
      GLP-1 secretion. More recently, it has been established that a diurnal regulation
      exists with incretin hormone secretion to an identical meal being greater when
      the meal is served in the morning compared to in the afternoon. Finally, whether
      incretin hormone secretion is altered in disease states is an area with, so far,
      controversial results in different studies, although some studies have
      demonstrated reduced incretin hormone secretion in type 2 diabetes. This review
      summarizes our knowledge on regulation of incretin hormone secretion and its
      potential changes in disease states.

PMID- 21094902
TI  - Using the lymph fistula rat model to study incretin secretion.
AB  - The past several decades have witnessed a flourish of interest in the field of
      incretin biology. The importance of the two incretin hormones, glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), in health
      and disease is becoming more apparent as the prevalence of type 2 diabetes and
      other metabolic disorders escalates. Rodent models have become indispensable in
      the study of the physiological function of GIP and GLP-1; however, investigators
      have run into several roadblocks when untangling the regulation of incretin
      secretion in these systems. The low circulating levels of the incretin hormones
      combined with sensitivity of the currently available assays require substantial
      amounts of blood to be removed from an animal if the hormones are to be analyzed
      over a period of time. Because of these limitations, continuous monitoring of GIP
      and GLP-1 secretion becomes difficult. A more effective means of studying
      incretin secretion in small animal models is therefore desirable. This chapter
      evaluates the use of the lymph fistula rat as a model to study the secretion of
      incretins. Lymph fistula models, in a variety of animals, have been used for
      decades to study the absorption and transport of lipid and lipophilic compounds;
      however, only recently has the value of this model been appreciated as a tool to
      explore incretin secretion.

PMID- 21094903
TI  - Structural basis for ligand recognition of incretin receptors.
AB  - The glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon
      like peptide-1 (GLP-1) receptor are homologous G-protein-coupled receptors
      (GPCRs). Incretin receptor agonists stimulate the synthesis and secretion of
      insulin from pancreatic beta-cells and are therefore promising agents for the
      treatment of type 2 diabetes. It is well established that the N-terminal
      extracellular domain (ECD) of incretin receptors is important for ligand binding
      and ligand specificity, whereas the transmembrane domain is involved in receptor
      activation. Structures of the ligand-bound ECD of incretin receptors have been
      solved recently by X-ray crystallography. The crystal structures reveal a similar
      fold of the ECD and a similar mechanism of ligand binding, where the ligand
      adopts an alpha-helical conformation. Residues in the C-terminal part of the
      ligand interact directly with the ECD and hydrophobic interactions appear to be
      the main driving force for ligand binding to the ECD of incretin receptors.
      Obviously, the-still missing-structures of full-length incretin receptors are
      required to construct a complete picture of receptor function at the molecular
      level. However, the progress made recently in structural analysis of the ECDs of
      incretin receptors and related GPCRs has shed new light on the process of ligand
      recognition and binding and provided a basis to disclose some of the mechanisms
      underlying receptor activation at high resolution.

PMID- 21094905
TI  - Central GLP-1 actions on energy metabolism.
AB  - Glucagon-like peptide 1 (GLP-1) is secreted mainly by the intestine in a nutrient
      dependent manner and stimulates glucose-induced insulin secretion, inhibits
      gastric emptying, food intake, and glucagon secretion. All these beneficial
      effects make GLP-1 as a promising, and currently in the market, drug candidate
      for the treatment of type 2 diabetes. More recently, it has been also
      demonstrated that within the central nervous system, GLP-1 also exerts important
      metabolic actions inhibiting food intake, increasing insulin secretion, and
      modulating behavioral responses. In this review, we will focus on the metabolic
      actions and mechanisms of the central GLP-1 system: modulation of energy intake,
      glucose metabolism, and fatty acid metabolism.

PMID- 21094904
TI  - Epac2-dependent rap1 activation and the control of islet insulin secretion by
      glucagon-like peptide-1.
AB  - Glucagon-like peptide-1 (GLP-1) binds its Class II G protein-coupled receptor to
      stimulate cyclic adenosine monophosphate (cAMP) production and to potentiate the
      glucose metabolism-dependent secretion of insulin from pancreatic beta cells
      located within the islets of Langerhans. Prior clinical studies demonstrate that
      this cAMP-mediated action of GLP-1 to potentiate glucose-stimulated insulin
      secretion (GSIS) is of major therapeutic importance when evaluating the abilities
      of GLP-1 receptor (GLP-1R) agonists to lower levels of blood glucose in type 2
      diabetic subjects. Surprisingly, recent in vitro studies of human or rodent
      islets of Langerhans provide evidence for the existence of a noncanonical
      mechanism of beta cell cAMP signal transduction, one that may explain how GLP-1R
      agonists potentiate GSIS. What these studies demonstrate is that a cAMP-regulated
      guanine nucleotide exchange factor designated as Epac2 couples beta cell cAMP
      production to the protein kinase A-independent stimulation of insulin exocytosis.
      Provided here is an overview of the Epac2 signal transduction system in beta
      cells, with special emphasis on Rap1, a Ras-related GTPase that is an established
      target of Epac2.

PMID- 21094906
TI  - Glucagon-like peptide-1 gastrointestinal regulatory role in metabolism and
      motility.
AB  - Gastrointestinal (GI) motility, primarily gastric emptying, balances the hormonal
      output that takes place after food intake in order to maintain stable blood
      sugar. The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic peptide (GIP), work together to reduce postprandial
      hyperglycemia by glucose-dependent insulin secretion and inhibition of glucagon
      release, as well as inhibition of GI motility and gastric emptying. GLP-1 is
      considered the more effective of the two incretins due to its additional
      inhibitory effects on GI motility. It is observed that patients on treatment with
      GLP-1 analogues or exenatide achieve a considerable weight loss during treatment.
      This is of benefit to improve insulin resistance in type 2 diabetes. Furthermore,
      weight loss per se is of considerable benefit in an even longer health
      perspective. The weight loss is considered to be due to the inhibition of GI
      motility. This effect has been studied in animal experimentation, and from there
      taken to involve studies on GI motility in healthy volunteers and patients with
      irritable bowel syndrome (IBS). Evolving to a phase II study in IBS, the GLP-1
      analogue (ROSE-010) was recently shown to be effective for treatment of acute
      pain attacks in IBS. Taken together, data speak in favor of GI motility as a
      central component not only in metabolic disorders but also in IBS, be it due to a
      direct relaxing effect on GI smooth muscle or a slow emptying of gastric contents
      resulting in a less outspoken nutritional demand on hormonal regulatory functions
      in the GI tract.

PMID- 21094907
TI  - The role of GLP-1 in neuronal activity and neurodegeneration.
AB  - Type 2 diabetes has been identified as a risk factor for Alzheimer's disease
      (AD). The underlying mechanism behind this unexpected link is most likely linked
      to the observed desensitization of insulin receptors in the brain. Insulin acts
      as a growth factor in the brain and supports neuronal repair, dendritic
      sprouting, and differentiation. Several drugs have been developed to treat type 2
      diabetes which re-synthesize insulin receptors and may be of use to prevent
      neurodegenerative developments in AD. The incretin glucagon-like peptide-1 (GLP
      1) is a hormone that facilitates insulin release under high blood sugar
      conditions. Interestingly, GLP-1 also has very similar growth factor like
      properties as insulin, and has been shown to protect neurons from toxic effects.
      In preclinical studies, GLP-1 and longer lasting analogues reduce apoptosis,
      protect neurons from oxidative stress, induce neurite outgrowth, protect synaptic
      plasticity and memory formation from the detrimental effects of beta-amyloid, and
      reduce plaque formation and the inflammation response in the brains of mouse
      models of AD. An advantage of GLP-1 is that it does not affect blood sugar levels
      in nondiabetic people. Furthermore, recent research has shown that some GLP-1
      analogues can cross the blood-brain barrier, including two that are on the market
      as a treatment for type 2 diabetes. Therefore, GLP-1 analogues show great promise
      as a novel treatment for AD or other neurodegenerative conditions.

PMID- 21094908
TI  - Wnt and incretin connections.
AB  - WNT signaling is emerging as a global regulator of metabolism, targeting multiple
      tissues. This is achieved either directly through Wnt receptors, or indirectly
      through the action of incretins, hormones that enhance glucose-stimulated insulin
      secretion and target extrapancreatic organs that cooperatively control whole body
      energy balance. WNT increases expression of incretins through evolutionarily
      conserved elements located within their proximal promoters. Wnt-responsive
      elements at the Incretin promoters may exhibit a high degree of selectivity for
      specific WNT effectors. Additionally, Incretins may modulate Wnt signaling and
      vice versa. Wnt-dependent modulation of incretin action in beta-pancreatic cells
      is suspected because the expression levels of Incretin receptors correlate with
      those of the Wnt effector TCF7L2. Conversely, Wnt signaling is enhanced by
      Incretin binding to their receptors which induces cAMP accumulation followed by
      stabilization of the Wnt effector: beta-catenin. High glucose and/or lipids
      control the number of Incretin receptors exhibited by beta cells. Whether these
      nutrients and/or the Incretins control Wnt receptors (either their expression or
      signaling) remains to be further elucidated. Thus, Wnt controls the expression of
      incretins and modulate their signaling at pancreatic cells. Signaling by Wnt and
      incretins appears to be interconnected at multiple levels. The in vivo
      significance of incretin induction by Wnt is unknown as it is the nature and
      origin of Wnt signals in enteroendocrine cells but opens an intense research that
      promises many surprises; in vitro approaches may be used for mechanistic studies
      and animal models for physiological perspectives.

PMID- 21094909
TI  - Incretin-based therapy and type 2 diabetes.
AB  - This chapter focuses on the incretin hormones, glucagon-like peptide-1 (GLP-1),
      and glucose-dependent insulinotropic polypeptide (GIP), and their therapeutic
      potential in treating patients with type 2 diabetes. Type 2 diabetes is
      characterized by insulin resistance, impaired glucose-induced insulin secretion,
      and inappropriately regulated glucagon secretion which in combination eventually
      result in hyperglycemia and in the longer term microvascular and macrovascular
      diabetic complications. Traditional treatment modalities--even multidrug
      approaches--for type 2 diabetes are often unsatisfactory at getting patients to
      glycemic goals as the disease progresses due to a steady, relentless decline in
      pancreatic beta-cell function. Furthermore, current treatment modalities are
      often limited by inconvenient dosing regimens, safety, and tolerability issues,
      the latter including hypoglycemia, body weight gain, edema, and gastrointestinal
      side effects. Therefore, the actions of GLP-1 and GIP, which include potentiation
      of meal-induced insulin secretion and trophic effects on the beta-cell, have
      attracted a lot of interest. GLP-1 also inhibits glucagon secretion and
      suppresses food intake and appetite. Two new drug classes based on the actions of
      the incretin hormones have been approved for therapy of type 2 diabetes:
      injectable long-acting stable analogs of GLP-1, incretin mimetics, and orally
      available inhibitors of dipeptidyl peptidase 4 (DPP4; the enzyme responsible for
      the rapid degradation of GLP-1 and GIP), the so-called incretin enhancers. In
      this chapter, we will describe the physiological effect of the incretin hormones-
      the incretin effect--in a historical perspective and focus on the two new classes
      of antidiabetic agents and will outline the scientific basis for the development
      of incretin mimetics and incretin enhancers, review clinical experience gathered
      so far, and discuss future expectations for incretin-based therapy.

PMID- 21094910
TI  - GPR119 agonists for the potential treatment of type 2 diabetes and related
      metabolic disorders.
AB  - Type 2 diabetes (T2D) has reached epidemic proportions, and there is an unmet
      medical need for orally effective agents that regulate glucose homeostasis.
      GPR119, a class-A (rhodopsin-like) G protein-coupled receptor expressed primarily
      in the pancreas and gastrointestinal tract, has attracted considerable interest
      as a T2D drug target in recent years. The activation of GPR119 increases the
      intracellular accumulation of cAMP, leading to enhanced glucose-dependent insulin
      secretion from pancreatic beta-cells and increased release of the gut peptides
      GLP-1 (glucagon-like peptide 1), GIP (glucose-dependent insulinotropic peptide)
      and PYY (polypeptide YY). Oral administration of small molecule GPR119 agonists
      has been shown to improve glucose tolerance in both rodents and humans. This
      review summarizes the research leading to the identification of GPR119 as a
      potential drug target for T2D and related metabolic disorders, and provides an
      overview of the recent progress made in the discovery of orally active GPR119
      agonists.

PMID- 21094912
TI  - Remote ischemic preconditioning: is the groove in the heart?

PMID- 21094913
TI  - The challenges of cost-effectiveness analyses for the clinician.

PMID- 21094914
TI  - The tradeoff between the risks of acute rejection and new-onset diabetes after
      kidney transplant.

PMID- 21094916
TI  - The importance of considering metabolism when indexing the GFR.

PMID- 21094917
TI  - Comparison of plasma clearance of iodixanol during versus after angiography.

PMID- 21094918
TI  - Foreword: the stress of writing about stress.

PMID- 21094919
TI  - Stress and immune-based diseases. Preface.

PMID- 21094920
TI  - Stress and autoimmunity.
AB  - Stress reduction interventions can have a positive therapeutic effect in
      autoimmune disease patients. Physicians and patients must recognize the potential
      for stress to impact autoimmune diseases and how stress management should be
      considered in a multidimensional treatment approach. This article evaluates the
      effects of stress as a trigger and a modulator, and stress reduction as a
      treatment option in rheumatoid arthritis.

PMID- 21094921
TI  - Epidemiology of stress and asthma: from constricting communities and fragile
      families to epigenetics.
AB  - Several epidemiologic frameworks, exemplified through extant research examples,
      provide insight into the role of stress in the expression of asthma and other
      allergic disorders. Biologic, psychological, and social processes interact
      throughout the life course to influence disease expression. Studies exploiting a
      child development framework focus on critical periods of exposure, including the
      in utero environment, to examine the influence of stress on disease onset. Early
      stress effects that alter the normal course of morphogenesis and maturation that
      affect both structure and function of key organ systems (eg, immune, respiratory)
      may persist into adult life underscoring the importance of a life course
      perspective. Other evidence suggests that maternal stress influences programming
      of integrated physiologic systems in their offspring (eg, neuroendocrine,
      autonomic, immune function) starting in pregnancy; consequently stress effects
      may be transgenerational. A multilevel approach that includes an ecological
      perspective may help to explain heterogeneities in asthma expression across
      socioeconomic and geographic boundaries that to date remain largely unexplained.
      Evolving studies incorporating psychological, behavioral, and physiologic
      correlates of stress more specifically inform underlying mechanisms operating in
      these critical periods of development. The role of genetics, gene by environment
      interactions, and epigenetic mechanisms of gene expression have been sparsely
      examined in epidemiologic studies on stress and asthma although overlapping
      evidence provides proof of concept for such studies in the future.

PMID- 21094922
TI  - Clinical potentials for measuring stress in youth with asthma.
AB  - It is well established that the course of asthma can be affected by the
      psychological stress an individual experiences. This article reviews literature
      assessing the effects of psychological stress on asthma outcomes and discusses
      the benefits and disadvantages of different measures for assessing stress,
      including subjective questionnaires, event checklists, and interview-based
      approaches. We discuss the importance of taking into account the timing and
      chronicity of stress, as well as individuals' subjective appraisals of stress. We
      suggest that, although questionnaire and checklist approaches are easier to
      administer, interview-based stress assessments are preferable, where feasible,
      because they generate richer and more in-depth information regarding the
      stressors that people experience. In addition, this kind of information seems to
      be more robustly linked to pediatric asthma outcomes of interest.

PMID- 21094923
TI  - Stress and allergic diseases.
AB  - Allergy describes a constellation of clinical diseases that affect up to 30% of
      the world's population. It is characterized by production of allergen-specific
      IgE, which binds to mast cells and initiates a cascade of molecular and cellular
      events that affect the respiratory tract (rhinitis and asthma), skin (dermatitis,
      urticaria), and multiple systems (anaphylaxis) in response to a variety of
      allergens including pollens, mold spores, animal danders, insect stings, foods,
      and drugs. The underlying pathophysiology involves immunoregulatory dysfunctions
      similar to those noted in highly stressed populations. The relationships in terms
      of potential for intervention are discussed.

PMID- 21094924
TI  - Stressor-induced alterations of adaptive immunity to vaccination and viral
      pathogens.
AB  - The stress response influences the immune system, and studies in laboratory
      animals indicate that the response to stress significantly reduces resistance to
      infectious challenge. Only a few studies, however, have determined the impact of
      the stress response on human susceptibility to infectious challenge due, in part,
      to the difficulties of using live, replicating pathogens in human research. As a
      result, many studies have assessed the immune response to vaccination as a
      surrogate for the immune response to an infectious challenge. Thus, much is known
      about how the stress response influences adaptive immunity, and memory responses,
      to vaccination. These studies have yielded data concerning the interactions of
      the nervous and immune systems and have provided important information for
      clinicians administering vaccines to susceptible populations. This review
      provides a brief overview of the immune response to commonly used vaccines and
      the impact that stress can have on vaccine-specific immunity.

PMID- 21094925
TI  - The impact of psychological stress on wound healing: methods and mechanisms.
AB  - Converging and replicated evidence indicates that psychological stress can
      modulate wound-healing processes. This article reviews the methods and findings
      of experimental models of wound healing. Psychological stress can have a
      substantial and clinically relevant impact on wound repair. Physiologic stress
      responses can directly influence wound-healing processes. Furthermore,
      psychological stress can indirectly modulate the repair process by promoting the
      adoption of health-damaging behaviors. Translational work is needed to develop
      innovative treatments able to attenuate stress-induced delays in wound healing.

PMID- 21094926
TI  - Neuroendocrine effects of stress on immunity in the elderly: implications for
      inflammatory disease.
AB  - Age-related changes in immune function leave older adults at risk for a host of
      inflammatory diseases. Immune-mediated inflammatory processes are regulated by
      neuroendocrine hormones, including glucocorticoids, dehydroepiandrosterone, and
      the catecholamines, epinephrine, and norepinephrine. This regulation, however,
      becomes impaired in older adults in light of age-related changes in endocrine
      function. Chronic stress shows similarly harmful effects on neuroendocrine and
      immune function and may, therefore, combine with age to further increase disease
      risk in older adults. This article highlights evidence for the impact of age and
      stress on neuroendocrine regulation of inflammatory processes that may
      substantially increase risk for inflammatory disease at older ages.

PMID- 21094929
TI  - Where do we stand in enzyme replacement therapy in Pompe's disease?

PMID- 21094928
TI  - The adverse effects of psychological stress on immunoregulatory balance:
      applications to human inflammatory diseases.
AB  - Psychological stress has known effects on the immune system, including impacting
      effector and regulatory components. This can result in increased susceptibility
      to various infections, latent virus reactivation, and impact on immunoregulatory
      circuits. One of the great challenges in translational research is defining the
      risks associated with stress in specific patient populations and individuals.
      Future studies must include identification and validation of biomarkers that can
      categorize patient risk for adverse immune effects from various forms and degrees
      of psychological stress and how this impacts the course of their inflammatory
      disease.

PMID- 21094930
TI  - Perspectives for IJS November issue.

PMID- 21094927
TI  - Biobehavioral influences on cancer progression.
AB  - This review focuses on the contributions of stress-related behavioral factors to
      cancer growth and metastasis and the biobehavioral mechanisms underlying these
      relationships. Behavioral factors that are important in modulation of the stress
      response and the pivotal role of neuroendocrine regulation in the downstream
      alteration of physiologic pathways relevant to cancer control, including the
      cellular immune response, inflammation, and tumor angiogenesis, invasion, and
      cell signaling pathways are described. Consequences for cancer progression and
      metastasis, as well as quality of life, are delineated. Behavioral and
      pharmacologic interventions with the potential to alter these biobehavioral
      pathways for patients with cancer are discussed.

PMID- 21094931
TI  - Polymeric membrane materials: new aspects of empirical approaches to prediction
      of gas permeability parameters in relation to permanent gases, linear lower
      hydrocarbons and some toxic gases.
AB  - Membrane gas separation technologies (air separation, hydrogen recovery from
      dehydrogenation processes, etc.) use traditionally the glassy polymer membranes
      with dominating permeability of "small" gas molecules. For this purposes the
      membranes based on the low free volume glassy polymers (e.g., polysulfone,
      tetrabromopolycarbonate and polyimides) are used. On the other hand, an
      application of membrane methods for VOCs and some toxic gas recovery from air,
      separation of the lower hydrocarbons containing mixtures (in petrochemistry and
      oil refining) needs the membranes with preferable penetration of components with
      relatively larger molecular sizes. In general, this kind of permeability is
      characterized for rubbers and for the high free volume glassy polymers. Data
      files accumulated (more than 1500 polymeric materials) represent the region of
      parameters "inside" of these "boundaries." Two main approaches to the prediction
      of gas permeability of polymers are considered in this paper: (1) the statistical
      treatment of published transport parameters of polymers and (2) the prediction
      using model of ?diffusion jump? with consideration of the key properties of the
      diffusing molecule and polymeric matrix. In the frames of (1) the paper presents
      N-dimensional methods of the gas permeability estimation of polymers using the
      correlations "selectivity/permeability." It is found that the optimal accuracy of
      prediction is provided at n=4. In the frames of the solution-diffusion mechanism
      (2) the key properties include the effective molecular cross-section of
      penetrating species to be responsible for molecular transportation in polymeric
      matrix and the well known force constant (epsilon/k)(eff i) of {6-12} potential
      for gas-gas interaction. Set of corrected effective molecular cross-section of
      penetrant including noble gases (He, Ne, Ar, Kr, Xe), permanent gases (H(2),
      O(2), N(2), CO), ballast and toxic gases (CO(2), NO(,) NO(2), SO(2), H(2)S) and
      linear lower hydrocarbons (CH(4), C(2)H(6), C(3)H(8), C(4)H(10), C(2)H(4),
      C(3)H(6), C(4)H(8) - 1, C(2)H(2), C(3)H(4)-m (methylacetylene) and C(3)H(4)-a
      (allen) is determined by using two above mentioned approaches. All of this allows
      calculating preliminary the permeability parameters of above mentioned gases for
      most part of known polymers based on limited experimental data. The new
      correlations suggested demonstrate that the available free volume of polymeric
      matrix plays an important role in providing of rate and selectivity of gas
      diffusion for glassy-like polymers; the rate and selectivity of gas diffusion in
      rubbers is affected mainly by cohesion energy density (CED) the both polymer
      parameters being calculated by traditional additive group contributions
      technique. Results of present study are demonstrated by calculation of expected
      permeability parameters in relation to lower hydrocarbons and some toxic gases
      for polynorbornene based polymers, PIM and PTMSP outlining potential of practical
      application for new membrane polymers.

PMID- 21094933
TI  - Tropoelastin and fibulin overexpression in the subepithelial connective tissue of
      human pterygium.
AB  - PURPOSE: To evaluate possible changes in the collagen and elastic components of
      the subepithelial connective tissue of human pterygium. DESIGN:
      Immunohistochemical study. METHODS: Immunohistochemical staining using
      antitropoelastin, anti-fibulin-2, and anti-fibulin-3 antibodies was performed in
      10 normal conjunctival and 20 pterygium specimens. Masson trichome staining also
      was performed to study subepithelial connective tissue. Sirius red staining was
      used to identify collagen type I and III components. Tropoelastin, fibulin-2, and
      fibulin-3 messenger ribonucleic acid (mRNA) expressions were analyzed in 9
      conjunctival and 12 pterygium specimens by quantitative real-time polymerase
      chain reaction assay. RESULTS: The subepithelial connective tissue and vessels
      were more predominant in pterygium compared with the normal conjunctival tissue.
      Amorphous subepithelial zones were observed in the areas of the pterygium tissue,
      but not in normal conjunctiva. Increased tropoelastin staining was seen in the
      pterygium tissue with areas of degenerative changes or immature formation of
      elastic fibers, as well an increase in tropoelastin mRNA, in contrast with
      fibulin-2 and fibulin-3 messenger levels. Fibulin-2 and fibulin-3 expression was
      colocalized in the subepithelial connective tissue and was distributed along
      blood and lymphatic vessels. Collagen type III, an immature form of collagen, was
      increased in the pathologic samples in association with a tissue remodeling
      process. CONCLUSIONS: Elastin metabolism is dysregulated in the pathogenesis of
      human pterygium with tropoelastin, fibulin-2, and fibulin-3 overexpression in the
      subepithelial connective tissue.

PMID- 21094934
TI  - Fourier-domain optical coherence tomography and microperimetry findings in
      retinitis pigmentosa.
AB  - PURPOSE: To investigate the relation between the optical coherence tomography
      (OCT) findings and retinal sensitivity in patients with retinitis pigmentosa (RP)
      by assessing the retinal thickness and retinal function using Fourier-domain OCT
      (FD-OCT) and microperimetry, respectively. DESIGN: Observational case series.
      METHODS: Fifty-nine patients (118 eyes) were enrolled, mean age 47 +/- 14.8
      years. Thirty-two healthy subjects (HS) were enrolled as a control group.
      Patients were assessed by means of FD-OCT and microperimetry. We analyzed the
      average foveal thickness (diameter of 1 mm centered on the point of fixation),
      the value of the retinal sensitivities corresponding to the 4 degrees centered on
      the fixation point, and logMAR visual acuity for regression analysis converted
      from Snellen chart. RESULTS: We distinguished 4 groups of RP patients according
      to the macular pattern seen on OCT images. The first group of 36 eyes, mean age
      of 33.5 +/- 7.4 years, had no macular changes, mean best-corrected visual acuity
      (BCVA) of 0.95 +/- 0.07, mean foveal thickness of 256.3 +/- 9.14 MUm, and mean
      retinal sensitivities inside the central 4 degrees of 19.27 +/- 0.87 dB (P > .05
      for all the values). The second group of 28 eyes, mean age 35.4 +/- 6.3 years,
      showed clinical macular edema (CME) on OCT images with mean BCVA of 0.72 +/-
      0.22, mean foveal thickness of 363.5 +/- 93.45 MUm, and mean retinal sensitivity
      inside the central 4 degrees of 15.94 +/- 3.6 dB (P < .01 for all the values).
      The third group of 26 eyes, mean age 50.8 +/- 8.7 years, showed macular
      vitreoretinal traction on OCT images with a mean BCVA of 0.5 +/- 0.2, mean foveal
      thickness of 337.1 +/- 71.7 MUm, and mean retinal sensitivity inside the central
      4 degrees of 11.78 +/- 3.09 dB (P < .01 for all the values). The last group of 28
      eyes, mean age 52.1 +/- 13.6 years, showed macular retinal thinning on OCT images
      with mean BCVA of 0.36 +/- 0.15, mean foveal thickness of 174.2 +/- 24.40 MUm,
      and mean retinal sensitivity inside the central 4 degrees of 10.22 +/- 3.82 dB (P
      < .01 for all the values). CONCLUSIONS: MP-1 and FD-OCT showed high sensitivity
      for identifying functional and structural macular abnormalities, respectively.
      Future studies should investigate the relationships among photoreceptor cell
      loss, retinal sensitivity, and fixation in patients with RP.

PMID- 21094932
TI  - The "Great Obstetrical Syndromes" are associated with disorders of deep
      placentation.
AB  - Defective deep placentation has been associated with a spectrum of complications
      of pregnancy including preeclampsia, intrauterine growth restriction, preterm
      labor, preterm premature rupture of membranes, late spontaneous abortion, and
      abruptio placentae. The disease of the placental vascular bed that underpins
      these complications is commonly investigated with targeted biopsies. In this
      review, we critically evaluate the biopsy technique to summarize the salient
      types of defective deep placentation, and propose criteria for the classification
      of defective deep placentation into 3 types based on the degree of restriction of
      remodeling and the presence of obstructive lesions in the myometrial segment of
      the spiral arteries.

PMID- 21094935
TI  - Retinal vessel diameter, retinal nerve fiber layer thickness, and intraocular
      pressure in korean patients with normal-tension glaucoma.
AB  - PURPOSE: To investigate the retinal vessel diameter and evaluate the relationship
      of the retinal nerve fiber layer (RNFL) thickness with retinal vessel diameter
      and intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG).
      DESIGN: A prospective, cross-sectional study. METHODS: This study included 60
      previously untreated patients with NTG (60 eyes) and 45 age- and sex-matched
      healthy controls (45 eyes) that had no history of systemic vascular disease at a
      single institution. The diameters of the central retinal arteries and veins were
      measured on retinal photographs. The central retinal arteriolar equivalent (CRAE)
      and central retinal venular equivalent (CRVE) were calculated using the revised
      Parr-Hubbard formula. The RNFL thickness was measured using Stratus optical
      coherence tomography. RESULTS: The mean central retinal arteriolar (P = .000) and
      venular (P = .000) diameters were significantly smaller in the eyes with NTG than
      in the normal eyes. Multivariate linear regression analysis demonstrated a
      significant positive correlation between the RNFL thickness and CRAE (P = .014),
      and a negative correlation between the RNFL thickness and IOP (P = .005) in the
      eyes with NTG. However, there was no significant correlation between the RNFL
      thickness and the independent variables in the control group (P = .112).
      CONCLUSION: The patients with NTG had smaller diameters of the central retinal
      vessels than the normal subjects. Both IOP and CRAE were significantly associated
      with RNFL thickness in the patients with NTG. Our results suggest that narrower
      retinal vessels and higher IOP may be related to the thinning of the RNFL in
      patients with NTG.

PMID- 21094936
TI  - Salivary levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of
      matrix metalloproteinase (TIMP)-1: a pilot study about the relationship with
      periodontal status and MMP-9(-1562C/T) gene promoter polymorphism.
AB  - OBJECTIVE: Chronic periodontitis (CP) has been linked with an imbalance in the
      MMP-9/TIMP-1 ratio. A reasonable biologic explanation for this link is that the
      MMP-9 transcriptional activity can be modulated by MMP-9(-1562C/T) gene promoter
      polymorphism contributing to periodontal breakdown. This study aimed to assess
      the relationship between salivary MMP-9/TIMP-1 balance, MMP-9(-1562C/T) genotype
      and periodontal clinical status. DESIGN: Sixty-nine CP subjects and 54 healthy
      controls (HC) were selected. Periodontal status was assessed by criteria based on
      probing depth, clinical attachment level, extent, and severity of periodontal
      breakdown. Salivary levels of MMP-9 and TIMP-1 were analysed using ELISA and MMP
      9(-1562C/T) genotype using the polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method. The association between salivary levels of
      MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio with CP was assessed individually and
      adjusted for confounding using a binary logistic regression model. RESULTS:
      Significantly higher levels of both markers and their ratios were detected in the
      CP group in comparison to healthy controls. Synchronously, weak-to-moderate
      positive significant correlations between salivary biomarkers and clinical
      parameters were observed. After binary logistic regression analysis, salivary
      levels of MMP-9>20ngmL(-1), TIMP-1>64ngmL(-1) as well as MMP-9/TIMP-1 ratio >1
      were independently associated with CP. Nevertheless, the MMP-9(-1562C/T) gene
      promoter polymorphism was not associated with the different degrees of chronic
      periodontitis and did not have influence on the salivary levels of biomarkers.
      CONCLUSION: The findings when considered within the limitations of this study may
      indicate that although a dominant expression of MMP-9 over TIMP-1 in saliva might
      reflect the periodontal clinical status, the functional polymorphisms in the
      promoter of the MMP-9(-1562C/T) gene from the Colombian population are not linked
      neither with significant salivary MMP-9 variations in these individuals nor
      periodontal clinical status.

PMID- 21094938
TI  - "Cool" inferior frontostriatal dysfunction in attention-deficit/hyperactivity
      disorder versus "hot" ventromedial orbitofrontal-limbic dysfunction in conduct
      disorder: a review.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and conduct disorder overlap
      behaviorally, clinically, and cognitively. An important question of potential
      future clinical relevance is whether these two overlapping disorders are mediated
      by similar or distinct underlying brain substrates. This article reviews the
      modern neuroimaging literature on brain structure, function, and connectivity in
      both disorders, shaping out commonalities and differences. Findings show that
      ADHD is characterized predominantly by abnormalities in inferior frontal,
      striatal, parietotemporal, and cerebellar regions and networks that mediate
      "cool"-cognitive, i.e., inhibitory, attention and timing functions associated
      with the disorder. Conduct disorder, by contrast, has consistently been
      associated with abnormalities of the "hot" paralimbic system that regulates
      motivation and affect, comprising lateral orbital and ventromedial prefrontal
      cortices, superior temporal lobes, and underlying limbic structures, most
      prominently the amygdala. Direct comparisons in functional imaging show that
      these associations of cool inferior fronto-striato-cerebellar dysfunction in ADHD
      and of hot orbitofrontal-paralimbic dysfunction in conduct disorder are disorder
      specific. There is, hence, evidence for dissociated underlying pathophysiologies
      for these two disorders that may have implications for future anatomy-based
      differential diagnosis and prevention and intervention.

PMID- 21094937
TI  - Hippocampal volume differences in Gulf War veterans with current versus lifetime
      posttraumatic stress disorder symptoms.
AB  - BACKGROUND: Decreased hippocampal volume is described in posttraumatic stress
      disorder (PTSD) and depression. However, it is not known whether it is a risk
      factor for the development of PTSD or a consequence of PTSD. We sought to
      determine the effects of PTSD and depressive symptoms on hippocampal volume.
      METHODS: Clinical and magnetic resonance imaging data were collected in a cross
      sectional study of 244 Gulf War veterans. Measures included lifetime and current
      Clinician Administered PTSD Scale, Hamilton Depression Scale, Life Stressor
      Checklist, and Lifetime Drinking History. Magnetic resonance imaging data were
      acquired with a 1.5-T scanner and analyzed with automated and semiautomated image
      processing techniques. RESULTS: Eighty-two veterans had lifetime PTSD, 44 had
      current PTSD, and 38 had current depression. In the linear regression analysis,
      current PTSD symptoms (standardized coefficient beta = -.25, p = .03) but neither
      lifetime PTSD symptoms nor current depression were associated with smaller
      hippocampal volume. Gender, age, history of early life trauma, education,
      lifetime and current alcohol use, current marijuana use, and treatment with
      antidepressants did not have independent effects. Participants with chronic PTSD
      had, on average, a smaller hippocampus compared with those with remitted PTSD.
      CONCLUSIONS: The finding that current but not lifetime PTSD symptom severity
      explains hippocampal size raises two possibilities: either a small hippocampus is
      a risk factor for lack of recovery from PTSD (trait) or PTSD effects on
      hippocampal volume are reversible once PTSD symptoms remit and the patient
      recovers (state).

PMID- 21094939
TI  - Habenula volume in bipolar disorder and major depressive disorder: a high
      resolution magnetic resonance imaging study.
AB  - BACKGROUND: Increased activity of the habenula has been implicated in the
      etiology of major depressive disorder (MDD), in which reductions in habenula
      volume are present after death. We conducted the first magnetic resonance imaging
      analysis of habenula volume in MDD and bipolar disorder (BD). METHODS: High
      resolution images (resolution approximately .4 mm(3)) were acquired with a 3T
      scanner, and a pulse sequence was optimized for tissue contrast resolution. The
      habenula was manually segmented by one rater blind to diagnosis. Seventy-four
      healthy control subjects (HC) were compared with both medicated
      (lithium/divalproex, n = 15) and unmedicated, depressed BD (n = 22) patients;
      unmedicated, depressed MDD patients (n = 28); and unmedicated MDD patients in
      remission (n = 32). RESULTS: The unmedicated BD patients displayed significantly
      smaller absolute (p < .01) and normalized (p < .05) habenula volumes than the HC
      subjects. In post hoc assessments analyzing men and women separately, the
      currently-depressed women with MDD had smaller absolute (p < .05) habenula
      volumes than the HC women. None of the other psychiatric groups differed
      significantly from the HC group. CONCLUSIONS: We provide further evidence for the
      involvement of the habenula in affective illness but suggest that a reduction in
      volume might be more pronounced in unmedicated, depressed BD subjects and female
      currently depressed MDD subjects. The habenula plays major roles in the long-term
      modification of monoamine transmission and behavioral responses to stress and in
      the suppression of dopamine cell activity after the absence of an expected
      reward. A reduction in habenula volume might thus have functional consequences
      that contribute to the risk for developing affective disease.

PMID- 21094940
TI  - IFN-gamma-induced BST2 mediates monocyte adhesion to human endothelial cells.
AB  - BST2 is a type II transmembrane protein that had been initially identified as a
      surface molecule expressed on terminally differentiated B cells. Here, we
      characterize the expression of BST2 in human endothelial cells, HUVECs. IFN
      gamma, among various inflammatory stimuli, dramatically upregulates BST2
      expression in HUVECs. We also address a novel putative role of BST2 in IFN-gamma
      stimulated HUVECs as an intercellular adhesion-related molecule. We show that
      purified extracellular domain of BST2 protein specifically and significantly
      decreased the adhesion of human monocytes to HUVECs, which suggests that IFN
      gamma-induced BST2 expression may be involved in monocyte migration from blood
      through the endothelium to the inflammation site. Furthermore, we show that the
      monocytic cell line U937 can directly adhere to BST2 extracellular domain-coated
      tissue culture wells. These results provide experimental evidence to support a
      novel role for BST2 in the interaction between human monocyte and IFN-gamma
      stimulated endothelium.

PMID- 21094941
TI  - Comparison of in vitro maturation media of immature oocytes: the effectiveness of
      blastocyst culture media.
AB  - OBJECTIVE: To compare three different in vitro maturation (IVM) media for
      immature oocytes. DESIGN: Experimental study. SETTING: In vitro fertilization
      laboratory. ANIMAL(S): BDF1 female and male mice. INTERVENTION(S): Retrieval and
      maturation of cumulus-enclosed germinal vesicle-stage oocytes according to one of
      three protocols: group A, conventional IVM medium; group B, blastocyst culture
      medium; and group C, tissue culture medium (TCM) 199. MAIN OUTCOME MEASURE(S):
      Maturation, fertilization, and developmental rates of immature oocytes.
      RESULT(S): A total of 653 immature oocytes were cultured in vitro and then
      analyzed. No difference was found in maturation rates and fertilization rates in
      comparing groups A and B. However, the IVM rates were statistically significantly
      increased in groups A and B compared with group C. No difference was found in
      fertilization rates between media, but the developmental competency to blastocyst
      stage was statistically significantly higher in group B compared with group C.
      CONCLUSION(S): The developmental competency of immature oocytes did not differ
      between conventional IVM medium and blastocyst culture medium, but TCM-199 was
      found to be unsuitable. Evidence from mice as test subjects suggests that both
      conventional IVM medium and blastocyst culture medium are suitable for IVM, and
      that blastocyst culture medium may be a good choice for conventional IVM of
      immature oocytes.

PMID- 21094943
TI  - Subjective health complaints in individuals with Ehlers-Danlos syndrome: a
      questionnaire study.
AB  - BACKGROUND: Ehlers-Danlos syndrome (EDS) is an inherited connective tissue
      disorder where symptoms such as hyper mobile joints, fragile tissues, a bleeding
      tendency and chronic pain are frequent. Consequently, functional disability is
      common. OBJECTIVE: In the present study we investigated the prevalence of
      subjective health complaints in a Swedish EDS group. DESIGN, PARTICIPANTS AND
      METHOD: Members of the Swedish EDS Association were invited to respond to the
      questionnaire Subjective Health Complaints Inventory (SHCI). Of the 365
      individuals receiving questionnaires, 250 diagnosed individuals >18 years (mean
      age 46.15; SD 12) responded. The overall response rate was 68% (females 89.2%;
      n=223). RESULTS: The total number of persons reporting any health complaint was
      247 (99%). The mean number of complaints was 16.1 (SD 5.7) in the whole group.
      The complaints reported were musculoskeletal by 246 (98%), pseudoneurological by
      241 (96%), gastrointestinal by 236 (94%), allergic by 182 (73%) and influenza
      like by 144 (58%) persons. Substantial complaints were reported by 240 (96%)
      persons. Women reported a significantly higher number of complaints, mean total
      SHC, and severity per complaint compared to men and the reference group; the
      Norwegian general population. CONCLUSION: Swedish females with EDS have higher
      number of and more substantial health complaints like tiredness and different
      localisations of pain than the compared Norwegian general population.
      Musculoskeletal, pseudoneurological and gastrointestinal complaints are most
      frequent in individuals with the hyper mobile EDS type.

PMID- 21094942
TI  - Psychometric properties of the Chinese version of the Parental Bonding
      Instrument.
AB  - BACKGROUND: The Parental Bonding Instrument (PBI) is a widely used assessment
      tool for measuring parental characteristics that affect parent-child bonds. The
      measure was developed for and has been most administered in Western populations.
      Psychometric analyses have yielded discrepant results as to whether the PBI is
      best represented by a two-factor model (care and overprotection) or a three
      factor model (care, overprotection, and autonomy). OBJECTIVES: Little is known
      about how the PBI performs in Chinese samples, and there is limited data from
      Eastern populations as a whole. The purpose of this study is to: (1) explore the
      data and identify the underlying structural model that best fits the Chinese
      culture, and (2) to further compare the factor structure that emerges in a
      Chinese sample with that which has emerged in other Eastern cultures (i.e.,
      Japanese) and Western countries. METHODS: The present study investigated the
      psychometric properties of a Chinese translation of the PBI among a sample
      (N=1417) of mothers of kindergarten children. Confirmatory factor analysis was
      used to identify the most adequate model. RESULTS: Results supported a four
      factor model that included an indifference factor (chi(2)/df<3.0; RMSEA<0.06;
      SRMR<0.08). Both the two-factor and three-factor models performed poorly
      (chi(2)/df>5.0; RMSEA>0.08; SRMR>1.0; CFI<0.90 for both). In this sample, use of
      a Chinese translated version of the PBI was successful. Support for the four
      factor model is consistent with findings from previous studies of Eastern
      populations and discrepant from those among Western samples. CONCLUSIONS: The
      indifference factor may reflect aspects of parenting specific to Eastern
      cultures, which tend to value group cohesion over individualization and
      independence. More research is needed to determine whether these findings are
      generalizable to all Eastern countries and whether aspects of Chinese culture
      (e.g., the single-child law) produce unique effects that may impact PBI
      administration in China.

PMID- 21094944
TI  - Dynamic stability of human walking in visually and mechanically destabilizing
      environments.
AB  - Understanding how humans remain stable during challenging locomotor activities is
      critical to developing effective tests to diagnose patients with increased fall
      risk. This study determined if different continuous low-amplitude perturbations
      would induce specific measureable changes in measures of dynamic stability during
      walking. We applied continuous pseudo-random oscillations of either the visual
      scene or support surface in either the anterior-posterior or mediolateral
      directions to subjects walking in a virtual environment with speed-matched optic
      flow. Floquet multipliers and short-term local divergence exponents both
      increased (indicating greater instability) during perturbed walking. These
      responses were generally much stronger for body movements occurring in the same
      directions as the applied perturbations. Likewise, subjects were more sensitive
      to both visual and mechanical perturbations applied in the mediolateral direction
      than to those applied in the anterior-posterior direction, consistent with
      previous experiments and theoretical predictions. These responses were likewise
      consistent with subjects' anecdotal perceptions of which perturbation conditions
      were most challenging. Contrary to the Floquet multipliers and short-term local
      divergence exponents, which both increased, long-term local divergence exponents
      decreased during perturbed walking. However, this was consistent with specific
      changes in the mean log divergence curves, which indicated that subjects'
      movements reached their maximum local divergence limits more quickly during
      perturbed walking. Overall, the Floquet multipliers were less sensitive, but
      reflected greater specificity in their responses to the different perturbation
      conditions. Conversely, the short-term local divergence exponents exhibited less
      specificity in their responses, but were more sensitive measures of instability
      in general.

PMID- 21094945
TI  - Spectral analysis and connectivity of porous microstructures in bone.
AB  - Cancellous bone is a porous composite of calcified tissue interspersed with soft
      marrow. Sea ice is also a porous composite, consisting of pure ice with brine,
      air, and salt inclusions. Interestingly, the microstructures of bone and sea ice
      exhibit notable similarities. In recent years, we have developed mathematical and
      experimental techniques for imaging and characterizing the brine microstructure
      of sea ice, such as its volume fraction and connectivity, as well as a range of
      theoretical approaches for studying fluid, thermal, and electromagnetic transport
      in sea ice. Here we explore the application of our sea ice techniques to
      investigate trabecular bone. For example, percolation theory that quantifies
      brine connectivity and its thermal evolution can also help assess the impact of
      osteoporosis on trabecular structure. Central to our approach is the spectral
      measure of a composite material, which contains detailed information about the
      mixture geometry, and can be used in powerful integral representations to compute
      the effective properties. The spectral measure is obtained from the eigenvalues
      and eigenvectors of a self-adjoint operator determined exclusively by the
      composite microgeometry. Here we compute the spectral measures for
      discretizations of images of healthy and osteoporotic bone. The measures are used
      to compute the effective electromagnetic properties of the bone specimens. These
      data are then inverted to reconstruct the porosity of the original specimens,
      with excellent agreement.

PMID- 21094946
TI  - Two-dimensional liquid chromatography/mass spectrometry/mass spectrometry
      separation of water-soluble metabolites.
AB  - Off-line two-dimensional liquid chromatography with tandem mass spectrometry
      detection (2D-LC/MS-MS) was used to separate a set of metabolomic species. Water
      soluble metabolites were extracted from Escherichia coli and Saccharomyces
      cerevisae cultures and were immediately analyzed using strong cation exchange
      (SCX)-hydrophilic interaction chromatography (HILIC). Metabolite mixtures are
      well-suited for multidimensional chromatography as the range of components varies
      widely with respect to polarity and chemical makeup. Some currently used methods
      employ two different separations for the detection of positively and negatively
      ionized metabolites by mass spectrometry. Here we developed a single set of
      chromatographic conditions for both ionization modes and were able to detect a
      total of 141 extracted metabolite species, with an overall peak capacity of ca.
      2500. We show that a single two-dimensional separation method is sufficient and
      practical when a pair or more of unidimensional separations are used in
      metabolomics.

PMID- 21094947
TI  - Comprehensive two-dimensional gas chromatography, retention indices and time-of
      flight mass spectra of flavonoids and chalcones.
AB  - The applicability of comprehensive two-dimensional gas chromatography (GC*GC) for
      flavonoids analysis was investigated by separation and identification of
      flavonoids in standards, and a complex matrix natural sample. The modulation
      temperature was optimized to achieve the best separation and signal enhancement.
      The separation pattern of trimethylsilyl (TMS) derivatives of flavonoids was
      compared on two complementary column sets. Whilst the BPX5/BPX50 (NP/P) column
      set offers better overall separation, BPX50/BPX5 (P/NP) provides better peak
      shape and sensitivity. Comparison of the identification power of GC*GC-TOFMS
      against both the NIST05 MS library and a laboratory (created in-house) TOFMS
      library was carried out on a flavonoid mixture. The basic retention index
      information on high-performance capillary columns with a non-polar stationary
      phase was established and database of mass spectra of trimethylsilyl derivatives
      of flavonoids was compiled. TOFMS coupled to GC*GC enabled satisfactory
      identification of flavonoids in complex matrix samples at their LOD over a range
      of 0.5-10 MUg/mL. Detection of all compounds was based on full-scan mass spectra
      and for each compound a characteristic ion was chosen for further quantification.
      This study shows that GC*GC-TOFMS yields high specificity for flavonoids derived
      from real natural samples, dark chocolate, propolis, and chrysanthemum.

PMID- 21094948
TI  - Development of a solid phase dispersion-pressurized liquid extraction method for
      the analysis of suspected fragrance allergens in leave-on cosmetics.
AB  - A new method based on solid phase dispersion-pressurized liquid extraction (PLE)
      followed by gas chromatography-mass spectrometry (GC-MS) has been developed for
      the determination of 26 suspected fragrance allergens (all the regulated in the
      EU Cosmetics Directive amenable by GC, as well as pinene and methyleugenol) in
      cosmetic samples. The effects of the temperature, extraction time and solvent,
      and dispersing sorbent, affecting the whole proposed procedure, have been
      evaluated using a multifactor strategy. The optima conditions after the analysis
      of main and second order effects entailed the extraction at 120 degrees C for 15
      min, using hexane/acetone as solvent, and florisil as dispersing sorbent. The
      method performance has been studied, showing good linearity (R>=0.996) as well as
      good precision (RSD<=10%). Detection limits (S/N=3) ranged from 0.000001 to
      0.0002% (w/w), values far below the established restrictions as regard labelling
      in the European Cosmetics Regulation. Reliability was demonstrated through the
      quantitative recoveries of all the studied compounds. The absence of matrix
      effects allowed quantification of the compounds by calibration with standard
      solutions. The analysis of 10 samples (several moisturizing and anti-wrinkle
      creams and lotions, hand creams, and sunscreen and after-sun creams), covering
      very different matrices, showed the presence of suspected allergens in all the
      analyzed samples; in fact, half of the samples contained an elevated number of
      them. Although the ubiquity of these compounds was demonstrated, labelling was in
      all cases in consonance with the European Cosmetics Regulation.

PMID- 21094949
TI  - Separation of nonionic surfactants according to functionality by hydrophilic
      interaction chromatography and comprehensive two-dimensional liquid
      chromatography.
AB  - It is shown, that amphiphilic polymers--such as polysorbates and fatty esters of
      polyethylene glycol can be separated by comprehensive two-dimensional liquid
      chromatography using a reversed phase column (under critical conditions for the
      polyoxyethylene chain) and a HILIC column, which may arranged in different order.
      The mobile phases in both dimensions can be 93-97 wt% acetone water. As the
      retention of higher esters on the reversed phase column is very strong, this
      column should be used as the first dimension. On the HILIC column all fractions
      elute within a reasonably short time (at a flow rate of 2.5 ml/min within 2 min).
      With a flow rate of 0.1 ml/min in the first dimension, a full separation can be
      achieved in 90 min.

PMID- 21094950
TI  - A simple high pH liquid chromatography-tandem mass spectrometry method for basic
      compounds: application to ephedrines in doping control analysis.
AB  - Solvent systems for use with LC-MS often result in a compromise between
      chromatographic performance and mass spectrometric detection, exemplified here by
      a LC-MS/MS method development for the analysis of ephedrines in doping control.
      Ephedrines, frequently found in therapeutic and nutritional preparations, are
      among the most commonly administered doping agents in competitive sport. Improved
      separation of these hydrophilic, basic compounds, some of which are
      diastereoisomers, is achieved in reversed-phase LC by the use of a high pH mobile
      phase in order to suppress analyte ionisation, and thus alter their polarity,
      resulting in reduced peak tailing and enhanced retention. However, when coupled
      to an ESI-MS detector, this eluent composition generated a non-linear and poorly
      reproducible signal. APCI yielded greater stability and reproducibility and is
      here presented as an ion source for the analysis of basic compounds under
      conditions that suppress their ionisation. Errors as large as 49.3% were observed
      with ESI, compared with 15.4% generated using APCI, for pseudoephedrine over the
      calibration range (25-400 MUg/mL) in urine with a simple dilution and injection
      of samples. These data highlight the importance of suitable MS conditions for
      stable performance, necessary for accurate quantification, without undue
      compromise to the LC separation.

PMID- 21094951
TI  - Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight
      preterm infants with patent ductus arteriosus.
AB  - OBJECTIVE: To compare oral ibuprofen with intravenous ibuprofen for closure of
      patent ductus arteriosus in very low birth weight (VLBW) preterm infants. STUDY
      DESIGN: In a prospective, randomized study, 102 VLBW preterm infants with patent
      ductus arteriosus received either intravenous or oral ibuprofen at an initial
      dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours. The success rate and
      evaluation of renal tolerance using cystatin-C were the major outcomes. RESULTS:
      Patent ductus arteriosus closure rate was significantly higher with oral
      ibuprofen (84.6% versus 62%) after the first course of the treatment (P = .011).
      The cystatin-C level increased significantly after treatment in the oral group (P
      = .001), but did not change with intravenous ibuprofen (P = .4). CONCLUSIONS:
      Oral ibuprofen is more effective than intravenous ibuprofen for ductal closure in
      VLBW infants. The increase in the cystatin-C level with oral treatment suggests
      that patients with borderline renal function should be evaluated and followed
      closely.

PMID- 21094952
TI  - Mental, motor, and language development of toddlers with neurofibromatosis type
      1.
AB  - OBJECTIVE: To examine the mental, motor, and language development of toddlers
      with neurofibromatosis type 1 (NF1). STUDY DESIGN: In this cross-sectional study,
      39 toddlers with NF1 (aged 21-30 months) and 42 age-matched control children were
      assessed using the Bayley Scales of Infant Development, Second Edition. Basic
      vocabulary was assessed with the language subtests from the Wechsler Preschool
      and Primary Scale of Intelligence, Third Edition. Parents completed
      questionnaires evaluating the children's expressive language, behavior, and
      executive functioning. The chi(2) test, independent t test, Mann-Whitney U test,
      and analysis of covariance were used to examine differences between the two
      groups. RESULTS: The toddlers with NF1 had significantly poorer mental and motor
      development than the control participants. Parental responses indicated that most
      of the children with NF1 had delayed language skills. No differences in behavior
      and executive functioning were noted between the two groups of children.
      CONCLUSIONS: Children with NF1 as young as age 30 months demonstrate early signs
      of mental, motor, and language difficulties. Age 2 years may be the appropriate
      time to perform an initial developmental assessment to identify mental, motor,
      and language impairments in children with NF1.

PMID- 21094953
TI  - Clinical monitoring guidelines for congenital hypothyroidism: laboratory outcome
      data in the first year of life.
AB  - OBJECTIVE: To examine whether current recommendations for thyroid status
      monitoring in children with congenital hypothyroidism (CH) (monthly in the first
      6 months and every 3-4 months subsequently) are adequate, or whether monthly
      monitoring is necessary throughout the first year. STUDY DESIGN: We reviewed
      charts of 70 children with CH for initial thyroid-stimulating hormone (TSH),
      frequency of follow-up, dose changes, and thyroxine (T(4)) and TSH levels in the
      first year. Need for monthly monitoring was determined on the basis of guidelines
      to maintain T(4)/free T(4) in the upper half of the normal range and rapidly
      normalize TSH. RESULTS: Monthly monitoring was justified in 75% in the first 6
      months and 36% in the next 6 months. Children requiring monthly monitoring in the
      second 6 months had higher baseline TSH (P = .02) and lower T(4) (P = .01) than
      those not requiring monthly monitoring. Thyroid dysgenesis, starting
      levothyroxine dose, sex, and ethnicity did not predict requirement for monthly
      monitoring. Thirty percent of children in the first and second 6 months had >=1
      high TSH level, with a T(4)/free T(4) not in the upper half of the normal range.
      CONCLUSION: More than a third of children with CH require monthly monitoring
      between 6 to 12 months on the basis of study criteria. Current monitoring
      guidelines may need to be reexamined.

PMID- 21094955
TI  - Chronic kidney disease and risk of death during hospitalization for stroke.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with higher stroke
      incidence, but little is known about the impact of CKD on mortality during stroke
      hospitalization, especially by CKD stage and index stroke type. This study
      assessed the effect of prevalent CKD on risk of dying in the hospital after a
      stroke. METHODS: Data were obtained from all US states that contributed to the
      Nationwide Inpatient Sample. All patients identified by the International
      Classification of Diseases, Ninth Revision procedure codes (n=1,127,842) admitted
      to hospitals between October 2005 and December 2006 with a discharge diagnosis of
      stroke were included. Independent associations of CKD with in-hospital mortality
      following stroke were evaluated using multivariable logistic regression. RESULTS:
      Of the sample, 64,985 (6%) had CKD, of which 5,785 (9%) died in the hospital. In
      multivariable analyses, CKD was associated with mortality overall (OR 1.63, 95%
      CI=1.52-1.75) and regardless of stroke type: ischemic stroke (OR 1.70, 95%
      CI=1.55-1.86), subarachnoid hemorrhage (OR 1.93, 95% CI=1.45-2.58), intracerebral
      hemorrhage (OR 1.28, 95% CI=1.10-1.49). Association between CKD and greater
      mortality was more pronounced in younger age groups (CKD*age interaction: p <
      0.0001) and in women vs. men (CKD*sex interaction: p < 0.0001). Higher CKD stage
      was associated with greater mortality odds, but only with Stages 5 (OR 3.21, 95%
      CI: 2.09-4.92) and 6 (OR 2.92, 95% CI: 2.62-3.25) was this association of
      significance. CONCLUSIONS: Presence of CKD is independently associated with
      higher odds of dying during stroke hospitalization regardless of index stroke
      type. This adverse association is driven by severe CKD and is more pronounced in
      relatively younger persons and women.

PMID- 21094954
TI  - Age-related differences in the clinical presentation of food-induced anaphylaxis.
AB  - Food-induced anaphylaxis may be more difficult to recognize in younger children.
      We describe age-related patterns in the clinical presentation of children with
      anaphylaxis, which may facilitate the early recognition and treatment of this
      potentially life-threatening condition.

PMID- 21094956
TI  - Effects of GABA(A) receptor blockade on regional cerebral blood flow and blood
      brain barrier disruption in focal cerebral ischemia.
AB  - In cerebral ischemia, transmission by the inhibitory neurotransmitter, gamma
      aminobutyric acid (GABA) is altered. This study was performed to determine
      whether blockade of GABA(A) receptor would affect regional cerebral blood flow
      (rCBF) and blood-brain barrier (BBB) permeability in a focal ischemic area of the
      brain. Rats were anesthetized with isoflurane and mechanically ventilated.
      Fifteen minutes after a permanent middle cerebral artery (MCA) occlusion, one
      half of the rats were infused with bicuculline 1mg/kg/min iv for 2 min followed
      by 0.1mg/kg/min iv to the end of the experiment. The other half were infused with
      normal saline. At one hour after MCA occlusion, rCBF was determined using 14C
      iodoantipyrine and BBB permeability was determined by measuring the transfer
      coefficient (Ki) of 14C-alpha-aminoisobutyric acid. With MCA occlusion, rCBF was
      decreased in the ischemic cortex (IC) (-70%) in the control rats. In the
      bicuculline treated rats, the rCBF of the IC was lower (-48%) than the
      contralateral cortex but higher than the rCBF of the IC of the control rats
      (+55%). MCA occlusion increased Ki in the IC of the control rats (+72%) and
      bicuculline administration increased Ki further (+53%) in the IC. Blockade of
      GABA(A) receptors did not significantly affect rCBF or BBB permeability in the
      non-ischemic brain regions under isoflurane anesthesia. Our data demonstrated
      that blockade of GABA(A) receptors increased rCBF and enhanced the BBB disruption
      in focal cerebral ischemia. Our data suggest that GABA(A) receptors are involved,
      at least in part, in modulating rCBF and BBB disruption in focal cerebral
      ischemia.

PMID- 21094958
TI  - Chronic non-paroxysmal neuropathic pain - Novel phenotype of mutation in the
      sodium channel SCN9A gene.
AB  - BACKGROUND: Gain-of-function mutations in the SCN9A gene (encoding to NaV1.7
      voltage-gated sodium channel) cause two rare paroxysmal pain disorders: inherited
      erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEDP). These
      phenotypes are characterized by episodic extreme localized pain with cutaneous
      autonomic signs. So far, no other phenotypes have been associated with mutation
      in the SCN9A gene. OBJECTIVE: To investigate mutations in the SCN9A gene in
      patients with chronic non-paroxysmal neuropathic pain. PATIENTS: 9 patients with
      chronic severe unexplained neuropathic pain. RESULTS: Of the nine patients one
      had predicted pathologic mutations in the SCN9A gene. This patient had a
      heterozygous change of n.4648 T-C in exon 27 resulting in a substitution of
      W1550R, a highly conserved amino acid, predicting damage in the transmembrane S2
      region, repeat IV. This mutation was not found in 50 controls. CONCLUSIONS: SCN9A
      mutations cause pain syndromes other than IEM and PEPD. These mutations should be
      considered in patients with resistant unexplained chronic neuropathic pain.

PMID- 21094959
TI  - Serial diffusion-weighted MRI and SPECT findings in a Creutzfeldt-Jakob disease
      patient with V180I mutation.
AB  - We report serial changes of diffusion-weighted imaging (DWI) and single photon
      emission computed tomography (SPECT) in a patient with Creutzfeldt-Jakob disease
      with V180I mutation (CJD180). DWI abnormalities in our patient were more
      predominantly observed in the left cerebral cortex than left basal ganglia.
      Hemilateral abnormalities progressed over 5 months to involve the contralateral
      side with increasing DWI signals. At 6 months, SPECT showed hypoperfusion in the
      left parietal and frontal lobes and the hypoperfusion region spread to the
      bilateral basal ganglia, right parietal and frontal lobes. SPECT imaging revealed
      marked cerebral blood flow reduction, predominantly in the cerebral cortex
      corresponding to brain areas with high-intensity DWI signals. During the follow
      up period of CJD180, DWI was more sensitive than conventional FLAIR and T2
      weighted images (T2WI) to detect and monitor the progression of abnormal
      hyperintense lesions. We suggest that serial DWI and SPECT findings are useful
      for not only early diagnosis of CJD but also for monitoring disease progression.

PMID- 21094960
TI  - Intracerebral haemorrhage, a possible presentation in Churg-Strauss syndrome:
      case report and review of the literature.
AB  - Churg-Strauss syndrome (CSS) is a rare systemic vasculitis, almost invariably
      accompanied by asthma, nasal polyposis, paranasal sinus abnormalities, and
      increased peripheral blood eosinophil count. Neurological involvement as
      peripheral neuropathy is a common feature, whereas cerebral involvement is
      extremely rare. Herein, we report the case of a young man who presented with
      sudden onset of right-side emiparesis and aphasia, whose head CT scan showed the
      presence of large haemorrhage in the left striatum nucleus involving part of the
      temporal lobe. Based on clinical and laboratory findings (asthma, eosinophilia
      >10%, paranasal sinus abnormalities and mononeuritis multiplex) a diagnosis of
      CSS was made. Cerebral angiography resulted normal, excluding the presence of
      vascular malformations or signs of vessel abnormalities. Pharmacotherapy with
      (intravenous and afterwards oral) corticosteroid and immunosuppressors
      (cyclophosphamide and then azathioprine) was initiated. The outcome was good with
      neurological follow-up showing a nearly complete recover. Our case points out
      that intracerebral haemorrhage can be, despite rare, a presenting feature of CSS.
      Previously reported patients affected by cerebral haemorrhage and CSS are
      summarized and briefly reviewed.

PMID- 21094961
TI  - Re: Fuhrman grade provides higher prognostic accuracy than nucleolar grade for
      papillary renal cell carcinoma: T. Klatte, C. Anterasian, J. W. Said, M. de
      Martino, F. F. Kabbinavar, A. S. Belldegrun and A. J. Pantuck J Urol 2010; 183:
      2143-2147.

PMID- 21094962
TI  - The atmospheric lead record preserved in lagoon sediments at a remote equatorial
      Pacific location: Palmyra Atoll, northern Line Islands.
AB  - Anthropogenic lead (Pb) inputs to the atmosphere increased greatly over the past
      century and now dominate Pb supply to the oceans. However, the Pb content of
      sediments across the equatorial Pacific region is relatively unknown, and data
      exist only for deep sea sites where Pb deposition lags surface water inputs by up
      to a century. Here we present ICP-MS analyses of Pb of a core from a lagoon at
      Palmyra Atoll, northern Line Islands, that spans approximately the past 160
      years. The non-bioturbated sediments of the euxinic lagoon, coupled with rapid
      rates of deposition, provide a unique fine-scale record of atmospheric Pb supply
      at a remote Pacific location. These first observations of historic Pb
      sedimentation in an atoll lagoon reveal a 63-fold increase in Pb flux to
      sediments during the past century and correlate directly with the North American
      consumption of leaded gasoline that began in 1926.

PMID- 21094963
TI  - [Neuro-ophthalmology in France in 2010].

PMID- 21094964
TI  - Fine structure of the female reproductive system in a viviparous insect, Glossina
      morsitans morsitans (Diptera, Glossinidae).
AB  - The female reproductive system of the tsetse fly Glossina morsitans morsitans is
      analysed by scanning electron microscopy (SEM). The study focuses in particular
      on the choriothete, a peculiar uterine structure involved in the viviparous mode
      of reproduction of Glossina morsitans morsitans. Under light microscopy, the
      choriothete appears formed by numerous tongue-like folds projecting towards the
      uterine lumen and lined by a thin cuticle. SEM analysis highlights for the first
      time a distinctive new feature that is not visible by traditional histological
      methods. That is a cuticular covering of the choriothete, which shows numerous
      thorns in the form of crest-like structures arranged in nearly parallel lines.
      The role of the choriothete in pregnancy and in larval nourishment is discussed.

PMID- 21094965
TI  - A Wavelet-Based Processing method for simultaneously determining ultrasonic
      velocity and material thickness.
AB  - Methods of measuring ultrasonic wave velocity in an elastic sample require data
      on the thickness of the sample and/or the distances between the transducers and
      the sample. The uncertainty of the ultrasonic wave velocity measurements
      generally depends on that of the data available. Conversely, to determine the
      thickness of a material, it is necessary to have a priori information about the
      wave velocity. This problem is particularly hard to solve when measuring the
      parameters of biological specimens such as bones having a greater acoustical
      impedance contrast (typically 3-5 MRayl) than that of the surrounding soft
      tissues (typically 1.5 MRayl). Measurements of this kind cannot easily be
      performed. But obtaining the thickness of a bone structure and/or the ultrasonic
      wave velocity is a important problem, for example, in biomechanical field for the
      calculation of elastic modulus, or in acoustical imaging field to parameterize
      the images, and to reference the grey or color level set to a physical parameter.
      The aim of the present study was to develop a method of simultaneously and
      independently determining the velocity of an ultrasonic wave in an elastic sample
      and the wave path across the thickness of this sample, using only one acquisition
      in pure transmission mode. The new method, which we have called the "Wavelet
      Based Processing" method, is based on the wavelet decomposition of the signals
      and on a suitable transmitted incident wave correlated with the experimental
      device, and the mathematical properties such as orthonormality, of which lend
      themselves well to the time-scale approach. By following an adapted algorithm,
      ultrasonic wave velocities in parallelepipedic plates of elastic manufactured
      material and the apparent thicknesses were both measured using a water tank, a
      mechanical device and a matched pair of 1MHz ultrasonic focused transducers
      having a diameter of 3mm, a focal length of 150mm and beam width of 2*2mm at the
      focus (mean temperature 22 degrees ). The results were compared with those
      obtained with a conventional Pulse-mode method and with the control values, to
      check their validity. Measurements performed on bovine and human dry cortical
      bone samples are also presented to assess the limitations of the method when it
      is applied to elastic biological samples, including those of an equal-wavelength
      size (~1.5mm). The thicknesses and the ultrasonic wave velocities were then
      measured in this kind of (quasi-) parallelepipedic elastic materials with an mean
      estimated error ranged from 1% to 3.5% compared to the referenced values.

PMID- 21094966
TI  - Simulation of ultrasonic lamb wave generation, propagation and detection for a
      reconfigurable air coupled scanner.
AB  - A computer simulator, to facilitate the design and assessment of a
      reconfigurable, air-coupled ultrasonic scanner is described and evaluated. The
      specific scanning system comprises a team of remote sensing agents, in the form
      of miniature robotic platforms that can reposition non-contact Lamb wave
      transducers over a plate type of structure, for the purpose of non-destructive
      evaluation (NDE). The overall objective is to implement reconfigurable array
      scanning, where transmission and reception are facilitated by different sensing
      agents which can be organised in a variety of pulse-echo and pitch-catch
      configurations, with guided waves used to generate data in the form of 2-D and 3
      D images. The ability to reconfigure the scanner adaptively requires an
      understanding of the ultrasonic wave generation, its propagation and interaction
      with potential defects and boundaries. Transducer behaviour has been simulated
      using a linear systems approximation, with wave propagation in the structure
      modelled using the local interaction simulation approach (LISA). Integration of
      the linear systems and LISA approaches are validated for use in Lamb wave
      scanning by comparison with both analytic techniques and more computationally
      intensive commercial finite element/difference codes. Starting with fundamental
      dispersion data, the paper goes on to describe the simulation of wave propagation
      and the subsequent interaction with artificial defects and plate boundaries,
      before presenting a theoretical image obtained from a team of sensing agents
      based on the current generation of sensors and instrumentation.

PMID- 21094967
TI  - Transmissible gastroenteritis virus (TGEV)-based vectors with engineered murine
      tropism express the rotavirus VP7 protein and immunize mice against rotavirus.
AB  - A coronavirus vector based on the genome of the porcine transmissible
      gastroenteritis virus (TGEV) expressing the rotavirus VP7 protein was constructed
      to immunize and protect against rotavirus infections in a murine model. The
      tropism of this TGEV-derived vector was modified by replacing the spike S protein
      with the homologous protein from mouse hepatitis virus (MHV). The rotavirus gene
      encoding the VP7 protein was cloned into the coronavirus cDNA. BALB/c and STAT1
      deficient mice were inoculated with the recombinant viral vector rTGEV(S-MHV)
      VP7, which replicates in the intestine and spreads to other organs such as liver,
      spleen and lungs. TGEV-specific antibodies were detected in all the inoculated
      BALB/c mice, while rotavirus-specific antibodies were found only after
      immunization by the intraperitoneal route. Partial protection against rotavirus
      induced diarrhea was achieved in suckling BALB/c mice born to dams immunized with
      the recombinant virus expressing VP7 when they were orally challenged with the
      homotypic rotavirus strain.

PMID- 21094969
TI  - Speciation and transport of arsenic in an acid sulfate soil-dominated catchment,
      eastern Australia.
AB  - Factors controlling the transport of geogenically-derived arsenic from a coastal
      acid sulfate soil into downstream sediments are identified in this study with
      both solid-phase associations and aqueous speciation clearly critical to the
      mobility and toxicity of arsenic. The data from both sequential extractions and X
      ray adsorption spectroscopy indicate that arsenic in the unoxidised Holocene acid
      sulfate soils is essentially non-labile in the absence of prolonged oxidation,
      existing primarily as arsenopyrite or as an arsenopyrite-like species, likely
      arsenian pyrite. Anthropogenically-accelerated pedogenic processes, which have
      oxidised this material over time, have greatly enhanced the potential
      bioavailability of arsenic, with solid-phase arsenic almost solely present as
      As(V) associated with secondary Fe(III) minerals present. Analyses of downstream
      sediments reveal that a portion of the arsenic is retained as a mixed
      As(III)/As(V) solid-phase, though not at levels considered to be environmentally
      deleterious. Determination of arsenic speciation in pore waters using high
      performance liquid chromatography/Inductively Coupled Plasma-Mass Spectrometry
      shows a dominance of As(III) in upstream pore waters whilst an unidentified As
      species reaches comparative levels within the downstream, estuarine locations.
      Pore water As(V) was detected at trace concentrations only. The results
      demonstrate the importance of landscape processes to arsenic transport and
      availability within acid sulfate soil environments.

PMID- 21094970
TI  - Effect of ultrasonication and Fenton oxidation on biodegradation of bis(2
      ethylhexyl) phthalate (DEHP) in wastewater sludge.
AB  - The presence of bis(2-ethylhexyl) phthalate (DEHP) and its metabolites, i.e. 2
      ethylhexanol, 2-ethylhexanal, and 2-ethylhexanoic acid in wastewater sludge (WWS)
      were investigated during aerobic digestion and Bacillus thuringiensis (Bt)-based
      fermentation of WWS. Ultrasonication and Fenton oxidation pre-treatment was
      applied to improve biodegradability of WWS and bioavailability of the target
      compounds for digestion and fermentation. DEHP and 2-ethylhexanoic acid were
      observed at higher concentration, meanwhile 2-ethylhexanol and 2-ethylhexanal
      were observed at lower concentration in WWS. After 20-day aerobic digestion, DEHP
      removal was 72%, 89%, and 85%, and 2-ethylhexanoic acid removal was 71%, 84%,
      79%, respectively for raw, ultrasonicated, and Fenton-oxidized sludges. Bt was
      found to degrade DEHP, leading to DEHP removal of 21%, 40%, and 30%, respectively
      for raw, ultrasonicated, and Fenton-oxidized sludges in the fermentation. The
      results suggested that aerobic stabilization and Bt-based fermentation can remove
      the phthalates, and pre-treatment of WWS was also effective in improvement of
      DEHP biodegradation. Hence, Bt-based biopesticide production from WWS can be
      applied safely when taking into consideration the phthalate contaminants.

PMID- 21094971
TI  - An on-farm survey of spatial and temporal stratifications of 17beta-estradiol
      concentrations.
AB  - 17beta-estradiol (E2) is a natural estrogenic hormone found in animal manure and
      urine, which may cause endocrine disruption in sensitive organisms. 17beta
      Estradiol has been widely detected in the environment, and animal agriculture may
      be an important source. The objectives of this study were to investigate the
      potential sources and/or spatial and temporal characteristics contributing to
      detections of E2 at the farm-scale. Soil cores, segmented into 0.15m increments,
      were taken down to the water table from four locations (three potential E2
      sources and one control) at or around a swine (Sus scrofa domesticus) farm on
      five different dates between 2006 and 2007. Estradiol was quantified in the soil
      water extracts using liquid chromatography-with tandem mass spectrometry
      (LC/MS/MS) analysis. Estradiol detections were widespread and found in 128 out of
      345 extractions (37%). Concentrations ranged from 0 to 1910 ng L-1 (porewater
      equivalents). A location that received field application of manure had
      significantly lower E2 concentrations compared to other locations. Also, the
      spring 2007 E2 concentrations were significantly higher than all other sample
      dates, perhaps related to climatic and hydrological events. Results suggested E2
      was not directly related to manure sources, but was widespread in this
      environment. Where E2 was detected, highest concentrations favored the upper
      profile, while the greatest frequency of detections was in the lower profile and
      near the water table. Detections of E2 were associated with high organic mater
      contents in the upper profile and high sand contents in the lower profile. The
      study suggests that E2 is widespread in some soil environments, raising questions
      as to the source and mechanisms that facilitate its transport and mobility.

PMID- 21094972
TI  - Physiological effects of mercury in the lichens Cladonia arbuscula subsp. mitis
      (Sandst.) Ruoss and Peltigera rufescens (Weiss) Humb.
AB  - This study aimed at investigating the cellular distribution of Hg in the lichens
      Cladonia arbuscula subsp. mitis and Peltigera rufescens treated with Hg2(+) and
      at testing if Hg treatment affects selected physiological parameters. In both
      species, increasing Hg accumulation under increasing Hg supply in the treatment
      solutions was found. P. rufescens showed a higher intracellular accumulation.
      Photosynthetic parameters were negatively affected in both species, as indicated
      by the decrease in photosynthetic pigments content, photosynthetic efficiency and
      chlorophyll integrity. Cell membranes of both species endured damage as indicated
      by the increase in the concentration of products of lipid peroxidation and
      decrease in ergosterol content. Nevertheless, differences between the two species
      were found, suggesting a differential sensitivity to Hg.

PMID- 21094973
TI  - Salting-out phenomenon and 1-octanol/water partition coefficient of metalaxyl
      pesticide.
AB  - In this paper, we present the effect of inorganic cations such as Na+, K+, Ca2+,
      Mg2+ on the salting-out phenomenon of metalaxyl from pure water to aqueous salt
      solutions. Moreover the 1-octanol/water partition coefficient in pure water is
      presented. To accomplish this, aqueous solubility of metalaxyl was determined in
      pure water, in different salt solution (NaCl, KCl, CaCl2 and MgCl2), and at
      different concentration level ranging from 0.01 to 1.5 M. The 1-octanol/water
      partition coefficient was determined using the static shake-flask method.
      Solubility was determined using dynamic saturation method for pure water in the
      range of 298.15-325.15 K and at 298.15 K for different salt solutions. The
      solubility value in pure water for studied interval was found constant
      (m=3.118*10(-2) mol kg(-1)). Solubility values were used to calculate the
      standard molar Gibbs free energy of dissolution (DeltasolG degrees ) and transfer
      (DeltatrG degrees ) at 298.15 K. The values of DeltatrG degrees  from pure to all
      studied aqueous salt solutions did not exceed 2 kJ mol(-1), the value of
      DeltasolG degrees  of dissolution is 18.5 +/-0.72 kJ mol(-1). The 1-octanol/water
      partition coefficient in pure water log Ko/w is equal to 1.69. The obtained
      results confirm the classification of the neutral metalaxyl as a slightly
      hydrophobic molecule.

PMID- 21094974
TI  - Distribution, source and risk assessment of polychlorinated biphenyls (PCBs) in
      urban soils of Beijing, China.
AB  - The concentration of PCBs in urban soils of Beijing across six land types
      including business districts (BD), cultural and educational areas (CE), classical
      gardens (CG), public green (PG), residential areas (RA), and roadsides (RD) was
      investigated. The total concentrations of PCBs ranged from below method detection
      limit (M.D.L.) to 37.11*10(-3)mgkg(-1) dry weight (mean: 11.70*10(-3)mgkg(-1);
      median: 13.28*10(-3)mgkg(-1)), which was at a medium level compared with other
      cities around the world. In general, the levels of PCBs decreased from the center
      of Beijing city to the suburb, suggesting the increasing PCBs concentrations with
      the age of the urban area. For different types of land use, the highest level of
      PCBs was observed in CG soils which have the oldest age, and the homologue
      profiles were similar, which were predominated by lowly chlorinated congeners
      including di-, tri- and tetra-CBs. Principal component analysis indicated that
      local sources such as Aroclor 1016, 1242, and 1248 were important sources in
      addition to long-range transport of PCBs all over the world. Although the toxic
      equivalency (TEQ) concentrations of dioxin-like PCBs in all soil samples of
      Beijing were higher than those in other urban areas of China, they met the
      Canadian soil quality standard.

PMID- 21094975
TI  - Phosphine migration at the water-air interface in Lake Taihu, China.
AB  - The diurnal atmospheric phosphine (PH3) concentrations and fluxes at the water
      air interface in Lake Taihu were reported. The results showed that the PH3 flux
      at the water-air interface ranged from -69.9+/-29.7 to 121+/-42 ng m(-2) h(-1),
      with a mean flux of 14.4+/-22.5 ng m(-2) h(-1). The fluxes were both negative and
      positive during the diurnal period, indicating that the lake can act as a sink
      and a source of PH3. In addition, the PH3 fluxes were positively correlated with
      water temperature, total soluble phosphorus and soluble reactive phosphorus,
      while they were negatively correlated with water redox potential. A similar
      diurnal variation curve of atmospheric PH3 concentrations was observed during all
      four seasons, with the maximum level occurring in early morning and the minimum
      appearing around midday. These findings suggest that light plays an important
      role in the elimination of atmospheric PH3. A significant positive correlation
      was also found between air temperature and atmospheric PH3 concentration. The
      mean flux of PH3 in Lake Taihu was higher than in other reported wetlands, with
      an estimated annual emission of PH3 to the atmosphere of 2.94*10(5) g y(-1).

PMID- 21094976
TI  - The role of a steel plant in north-west Italy to the local air concentrations of
      PCDD/Fs.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) are ubiquitous contaminants, mainly released into the environment during
      combustion processes (point sources), but also from other sources (traffic,
      uncontrolled combustion). This study aims at investigating the contribution of a
      steel plant in NW Italy (700000tons of steelyear(-1)) to the air concentrations
      of PCDDs/PCDFs at local level, through the analysis of measured, modelled and
      literature data. The study was carried out in an area of 600km(2), using air
      quality data measured by the institutional monitoring network, data obtained from
      AERMOD simulations and literature data. The measured air concentrations were
      consistent with literature values for similar areas, and both the homologue
      profiles and PCA analyses showed a clear distinction between the monitoring
      stations and the source profiles. All the previous results were confirmed by the
      air dispersion model (AERMOD), that predicted PCDD/F air concentrations due to
      the steel plant from four to two orders of magnitude lower than those measured in
      the monitoring stations, highlighting the presence of other sources. This study
      outlines the limited influence of the source in the local PCDD/F air
      concentrations and at the same time the usefulness of a joint analysis of
      measured, literature and calculated data to correctly evaluate the role of a
      source to the local pollution. The study also highlights the usefulness of AERMOD
      as a complementary tool to define the correct placement of monitoring stations
      and to locate those areas expected to have the highest air concentrations
      deriving from a source.

PMID- 21094978
TI  - Role of microbial exopolymeric substances (EPS) on chromium sorption and
      transport in heterogeneous subsurface soils: II. Binding of Cr(III) in EPS/soil
      system.
AB  - Laboratory batch sorption and column experiments were performed to investigate
      the effects of microbial EPSs isolated from Pseudomonas putida P18, Pseudomonas
      aeruginosa P16 and Pseudomonas stutzeri P40 on Cr(III) mobility in heterogeneous
      subsurface soils. Our batch and column results indicate that microbial EPS may
      have a pronounced effect on Cr(III) sorption and transport behavior depending on
      system conditions (e.g., pH, type of EPS). While EPS had no effect on Cr(III)
      sorption at pH<5, it led to a significant decrease in Cr(III) sorption under
      slightly acidic to alkaline pH range. Column experiments performed at pH 7.9
      suggest that, in the presence of EPS, chromium(III) was significantly mobilized
      relative to non-EPS containing system due to the formation less sorbing and
      highly soluble Cr-EPS complexes and competition of EPS against Cr for surface
      sites. A two-site non-electrostatic surface chemical model incorporating a
      discrete ligand approach for the description of Cr-EPS interactions accurately
      predicted Cr(III) sorption and transport behavior in the presence of EPS under
      variable chemical conditions. Our simulations show that an accurate description
      of Cr(III) transport in the presence of EPS requires incorporation of proton and
      Cr(III) binding by EPS, EPS binding by soil minerals, Cr(III) binding by soil
      minerals, and ternary Cr(III)-EPS surface complexes into the transport equations.
      Although this approach may not accurately describe the actual mechanisms at the
      molecular level, it can improve our ability to accurately describe the effects of
      EPS on Cr(III) mobility in subsurface environment relative to the use of
      distribution coefficients (K(d)).

PMID- 21094977
TI  - Sorption of thallium(I) onto geological materials: influence of pH and humic
      matter.
AB  - The sorption behaviour of the severely toxic heavy metal thallium (Tl) as a
      monovalent cation onto three representative materials (goethite, pyrolusite and a
      natural sediment sampled from a field site) was examined as a function of pH in
      the absence and presence of two natural humic acids (HAs), using 204Tl(I) as a
      radiotracer. In order to obtain a basic understanding of trends in the pH
      dependence of Tl(I) sorption with and without HA, sorption of HAs and humate
      complexation of Tl(I) as a function of pH were investigated as well. In spite of
      the low complexation between Tl(I) and HAs, the presence of HAs results in
      obvious alterations of Tl(I) sorption onto pyrolusite and sediment. An influence
      on Tl(I) sorption onto goethite was not observed. Predictions of Kd (distribution
      coefficient) for Tl(I) on goethite in the presence of HAs, based on a linear
      additive model, agree well with the experimental data, while a notable
      disagreement occurs for the pyrolusite and sediment systems. Accordingly, it is
      suggested that HAs and goethite may act as a non-interacting sorbent mixture
      under the given conditions, but more complex interactions may take place between
      the HAs and the mineral phases of pyrolusite or sediment.

PMID- 21094979
TI  - Sorption of polycyclic aromatic hydrocarbons (PAHs) on glass surfaces.
AB  - Sorption of polycyclic aromatic hydrocarbons (PAHs) to glass commonly used in
      laboratories was studied. Sorption coefficients (Kd) of five selected PAHs to
      borosilicate glass surfaces were measured using column chromatography. A linear
      relationship between log Kd and the corresponding water solubility of the
      subcooled liquid (log Sw) of the investigated PAHs was observed. Based on the
      determined sorption coefficients our data revealed that mass loss caused by
      sorption on glass walls strongly depends on the ratio of solution volume to
      contacted surface area (V/S). The influence of solution chemistry such as ionic
      strength, solution pH, presence of cosolvent, and the influence of temperature on
      the sorption process were investigated. In the presence of ionic strength,
      sorption coefficients concurrently increased but less than a factor of 2 up to
      0.005 M calcium chloride concentration. However, further increasing ionic
      strength had no influence on Kd. The cosolvent reduced sorption at a
      concentration of methanol in water above 0.5% (v/v); however, for benzo[a]pyrene
      even with 10% (v/v) methanol the mass loss would be still higher than 10% (with a
      V/S ratio less than 0.25). Significant effects of the solution pH and temperature
      were not observed. These results suggest that van der Waal's forces dominate the
      sorption process. In the analysis of highly hydrophobic PAHs in aqueous samples,
      mass loss due to sorption on glass walls should be accounted for in the final
      result if untreated glass is used. The presented relationship between log Kd and
      log Sw may help to decide if such a correction is necessary. Furthermore, the
      frequently used silanization of glass surfaces may not be sufficient to suppress
      sorption for large PAHs.

PMID- 21094980
TI  - Biodegradation of 4-aminobenzenesulfonate by Ralstonia sp. PBA and Hydrogenophaga
      sp. PBC isolated from textile wastewater treatment plant.
AB  - A co-culture consisting of Hydrogenophaga sp. PBC and Ralstonia sp. PBA, isolated
      from textile wastewater treatment plant could tolerate up to 100 mM 4
      aminobenzenesulfonate (4-ABS) and utilize it as sole carbon, nitrogen and sulfur
      source under aerobic condition. The biodegradation of 4-ABS resulted in the
      release of nitrogen and sulfur in the form of ammonium and sulfate respectively.
      Ninety-eight percent removal of chemical oxygen demand attributed to 20 mM of 4
      ABS in cell-free supernatant could be achieved after 118 h. Effective
      biodegradation of 4-ABS occurred at pH ranging from 6 to 8. During batch culture
      with 4-ABS as sole carbon and nitrogen source, the ratio of strain PBA to PBC was
      dynamic and a critical concentration of strain PBA has to be reached in order to
      enable effective biodegradation of 4-ABS. Haldane inhibition model was used to
      fit the degradation rate at different initial concentrations and the parameters
      MU(max), K(s) and K(i) were determined to be 0.13 h-1, 1.3 mM and 42 mM
      respectively. HPLC analyses revealed traced accumulation of 4-sulfocatechol and
      at least four unidentified metabolites during biodegradation. This is the first
      study to report on the characterization of 4-ABS-degrading bacterial consortium
      that was isolated from textile wastewater treatment plant.

PMID- 21094981
TI  - Hematological, biochemical and ionoregulatory responses of Indian major carp
      Catla catla during chronic sublethal exposure to inorganic arsenic.
AB  - In the present study the acute toxicity of arsenic trioxide in fingerlings of
      Catla catla an Indian major carp was evaluated with renewal bioassay method. The
      median lethal concentration of arsenic trioxide to the fish C. catla for 96 h was
      found to be 20.41 ppm (with 95% confidence limits). From this a non-lethal dose
      of (2.041 ppm; 1/10th of LC 50 96 value) was selected and fingerlings were
      exposed to 35 d and hematological, biochemical and ionoregulatory responses were
      studied at days 7, 14, 21, 28 and 35. Arsenic trioxide produced a significant
      increase in hemoglobin, hematocrit, WBC count, plasma GPT levels and reduction in
      RBC count, plasma sodium, chloride, potassium, glucose, protein, GOT, LDH levels
      as compared to the control group. Gill Na(+)/K(+)-ATPase activity was influenced
      by arsenic trioxide exposure. A biphasic response was noted in the value of MCH
      and MCV. However the MCHC level was not altered in arsenic trioxide treated fish
      throughout the study period. Results of the present investigation suggest that
      arsenic trioxide affects the hematological, biochemical and ionoregulatory
      parameters of fish and alterations of these parameters can be useful in
      environmental biomonitoring of arsenic contamination.

PMID- 21094982
TI  - Gene polymorphisms of glutathione S-transferase omega 1 and 2, urinary arsenic
      methylation profile and urothelial carcinoma.
AB  - Genetic polymorphisms in arsenic-metabolizing enzymes may be involved in the
      biotransformation of inorganic arsenic and may increase the risk of developing
      urothelial carcinoma (UC). The present study evaluated the roles of glutathione S
      transferase omega 1 (GSTO1) and GSTO2 polymorphisms in UC carcinogenesis. A
      hospital-based case-control study was conducted. Questionnaire information and
      biological specimens were collected from 149 UC cases and 251 healthy controls in
      a non-obvious inorganic arsenic exposure area in Taipei, Taiwan. The urinary
      arsenic profile was determined using high-performance liquid chromatography and
      hydride generator-atomic absorption spectrometry. Genotyping for GSTO1 Ala140Asp
      and GSTO2 Asn142Asp was conducted using polymerase chain reaction-restriction
      fragment length polymerase. GSTO1 Glu208Lys genotyping was performed using high
      throughput matrix-assisted laser desorption and ionization time-of-flight mass
      spectrometry. A significant positive association was found between total arsenic,
      inorganic arsenic percentage and monomethylarsonic acid percentage and UC, while
      dimethylarsinic acid percentage was significantly inversely associated with UC.
      The minor allele frequency of GSTO1 Ala140Asp, GSTO1 Glu208Lys and GSTO2
      Asn142Asp was 18%, 1% and 26%, respectively. A significantly higher MMA% was
      found in people who carried the wild type of GSTO1 140 Ala/Ala compared to those
      who carried the GSTO1 140 Ala/Asp and Asp/Asp genotype (p=0.02). The homogenous
      variant genotype of GSTO2 142 Asp/Asp was inversely associated with UC risk
      (OR=0.17; 95% CI, 0.03 - 0.88; p=0.03). Large-scale studies will be required to
      verify the association between the single nucleotide polymorphisms of arsenic
      metabolism-related enzymes and UC risk.

PMID- 21094983
TI  - Functional analysis of three recombinant A1-VWF domain mutants in comparison to
      wild type and plasma-derived VWF facilitates subtyping in type 2 von Willebrand
      disease.
AB  - Phenotypic diagnosis of VWD, in particular type 2, is challenging. Molecular
      diagnosis may fail to provide clarity since mutations within a short stretch of
      the same domain may cause various phenotypes, and since even experts will ascribe
      different subtypes to similar mutations. We assessed diagnostic difficulty in VWD
      by investigating five cases where phenotypic data was unclear. We identified 3
      novel mutations within the A1 domain of the VWF gene: L1460F (2 related
      patients), Y1363C (1 patient), E1389K (2 related patients). These were not found
      in 100 normal individuals or documented in the VWF mutation database. Detailed
      functional analysis of recombinant mutants included VWF multimers, VWF:Ag,
      VWF:RCo, VWF:CB, and Platelet-VWF binding studies, and results assessed against
      recombinant WT and plasma derived (pd) VWF. Multimer analysis showed clear loss
      of HMW VWF with E1389K only, consistent with coincident low relative CB/Ag ratio.
      VWF-platelet binding studies using two independent approaches showed enhanced
      activity for L1460F, but reduced activity for E1389K and Y1363C. A novel finding
      was that WT rVWF showed enhanced platelet binding in RIPA analysis compared to
      pdVWF with this being dependent on the dilution material used. Through these
      extensive studies, we assigned L1460F to type 2B, E1389K to 2A, and Y1363C to 2M
      VWD. Thus, although molecular analysis is not required to classify VWD patient
      subtypes, a thorough and combined phenotypic, genotypic and functional analysis
      will assist assignment of the VWD subtype.

PMID- 21094984
TI  - Plasma factor VII: a potential marker of pre-eclampsia.
AB  - INTRODUCTION: Normal pregnancy is associated with a local hypercoagulable state
      that becomes more profound in certain obstetric complications such pre-eclampsia
      (P-EC). Current literature on the levels of individual haemostatic factors in
      women with P-EC is limited and results are inconsistent. In this study we provide
      detailed investigation on the tissue factor (TF)-dependent pathway in women with
      P-EC. MATERIALS AND METHODS: Enzyme-linked immunosorbent assays (ELISA) were used
      to measure plasma factor (F) FVII, FVIIa, TF and tissue factor pathway inhibitor
      (TFPI) in healthy non-pregnant women (n = 22), normal pregnant women (n = 15),
      and women with P-EC (n = 20). All subjects were age matched. In addition,
      pregnant women were matched for gestational age, parity and were all at the third
      trimester. RESULTS: Plasma FVII levels were significantly higher in women with P
      EC compared to the healthy non-pregnant (P<0.001) or the normal pregnant groups
      (P<0.001). No such significant trends were observed for plasma FVIIa, TF or TFPI
      levels. Plasma FVII levels can distinguish women with P-EC from healthy non
      pregnant women or normal pregnant women at the third trimester, with high
      sensitivity (90%), specificity (80%), positive and negative predictive values
      (86%). CONCLUSIONS: Plasma FVII levels are significantly elevated in women with P
      EC, in the absence of comparable changes in other TF-dependent pathway factors
      (FVIIa, TF and TFPI). We propose the use of plasma FVII as a marker for P-EC.

PMID- 21094985
TI  - Comparison of the Wells score with the simplified revised Geneva score for
      assessing pretest probability of pulmonary embolism.
AB  - INTRODUCTION: The Wells score is widely used in the assessment of pretest
      probability of pulmonary embolism (PE). The revised Geneva score is a fully
      standardized clinical decision rule that was recently validated and further
      simplified. We compared the predictive accuracy of these two scores. METHODS:
      Data from 339 patients clinically suspected of PE from two prospective management
      studies were used and combined. Pretest probability of PE was assessed
      prospectively by the Wells score. The simplified revised (SR) Geneva score was
      calculated retrospectively. The predictive accuracy of both scores was compared
      by area under the curve (AUC) of receiver operating characteristic (ROC) curves.
      RESULTS: The overall prevalence of PE was 19%. Prevalence of PE in the low,
      moderate and high pretest probability groups assessed by the Wells score and by
      the simplified revised Geneva score was respectively 2%(95% CI (CI) 1-6) and 4%
      (CI 2-10), 28% (CI 22-35) and 25% (CI 20-32), 93% (CI 70-99) and 56% (CI 27-81).
      The Wells score performed better than the simplified revised Geneva score in
      patients with a high suspicion of PE (p<0.05). The AUC for the Wells score and
      the simplified revised Geneva score was 0.85 (CI: 0.81 to 0.89) and 0.76 (CI:
      0.71 to 0.80) respectively. The difference between the AUCs was statistically
      significant (p=0.005). CONCLUSIONS: In our population the Wells score appeared to
      be more accurate than the simplified revised Geneva score. The impact of this
      finding in terms of patient outcomes should be investigated in a prospective
      study.

PMID- 21094987
TI  - A new method measuring the interaction between von Willebrand factor and
      coagulation factor VIII.
AB  - INTRODUCTION: There is a need for more reliable methods measuring the binding of
      coagulation factor VIII (FVIII) to von Willebrand factor (VWF) in plasma samples,
      for use in the clinical routine. We have developed such a method measuring FVIII
      binding in plasma, utilizing an ELISA system. MATERIALS AND METHODS: Microtiter
      plates were coated with a monoclonal antibody (ESH-8), reacting with the C2
      domain in FVIII. Thereafter the wells were treated with recombinant FVIII
      (Kogenate Bayer(r)). After washing, diluted plasma samples were added and
      incubated for 1h. Then HRP-conjugated antibodies against VWF were added and used
      for quantification of bound VWF. RESULTS: A strong signal to VWF concentration
      response was obtained. Plasma from patients with different types of von
      Willebrand disease gave frequently diminished responses. However, after
      correction for the VWF antigen levels, by calculation of FVIII binding/VWF
      antigen ratio, only the patients with known von Willebrand disease type 2N (n =
      4) had clearly abnormal results. The FVIII binding in 40 healthy individuals was
      determined as 1.08 +/- 0.48 U/mL (SD). After correction for the VWF antigen
      levels the result was 0.94 +/- 0.15. Thus, the SD declined substantially by this
      correction. The within-series CV and between-series CV were determined as 6.8 and
      11.3%, respectively. CONCLUSIONS: We have established a simple and reliable
      method to detect decreased binding of FVIII to von Willebrand factor in plasma
      samples. The method can conveniently be used to study large populations, as well
      as finding minor binding defects in patients.

PMID- 21094986
TI  - Platelets as initiators and mediators of inflammation at the vessel wall.
AB  - Platelets are dynamic cells with activities that extend beyond thrombosis
      including an important role in initiating and sustaining vascular inflammation. A
      role for platelets has been described in many physiologic and pathophysiologic
      processes such as atherosclerosis, stem cell trafficking, tumor metastasis, and
      arthritis. Platelet activation at sites of an intact inflamed endothelium
      contributes to vascular inflammation and vascular wall remodeling. Platelets
      secrete a wide array of preformed and synthesized inflammatory mediators upon
      activation that can exert significant local and systemic effects. This review
      will focus on the role of platelet derived mediators in vascular inflammation and
      vascular wall remodeling.

PMID- 21094988
TI  - Xanthogranulomatous pyelonephritis with unconnected liver lesion.
AB  - Xanthogranulomatous pyelonephritis is a chronic renal inflammation characterized
      by destruction and replacement of its parenchyma with granulomatous tissue. This
      uncommon condition is rare in children. We report on a 5-month-old male infant
      with a left renal and hepatic mass detected by ultrasound. The case was
      preoperatively misdiagnosed as Wilms' tumor and total nephrectomy and biopsy from
      liver lesion were performed. The subsequent histopathological findings confirmed
      the diagnosis of xanthogranulomatous pyelonephritis for renal and liver lesions.
      Increasing awareness of this disease should lead to the diagnosis being suspected
      preoperatively even if it is with unconnected tissue lesions.

PMID- 21094989
TI  - Higher proportion of haploid round spermatids and spermatogenic disomy rate in
      relation to idiopathic male infertility.
AB  - OBJECTIVES: To investigate the possible association between the spermatogenic
      chromosomal aberrations and idiopathic male infertility with normal semen volume,
      sperm concentration, sperm number per ejaculum, and sperm motility. Male
      infertility can be considered as a syndrome that results from many congenital or
      acquired illness. Currently, there is an increasing awareness of the potential
      role of chromosomal factors in the idiopathic forms of male infertility. METHODS:
      A total of 202 idiopathic infertile men and 41 normal fertile donors were
      recruited into this study, through eligibility screening procedures. Proportions
      and chromatin status of sperm were assessed by flow cytometry after staining the
      DNA with propidium iodide. Sperm chromosome aneuploidy rates for chromosome 13,
      18, 21, X, and Y were evaluated by fluorescence in situ hybridization using five
      color probes. RESULTS: Infertile males showed a significantly lower percentage of
      mature haploid sperm cells and higher percentage of haploid round spermatids than
      the controls. A significantly higher frequency of disomy on spermatozoa was also
      detected in infertile males compared with the controls. CONCLUSIONS: These
      findings suggest that higher frequencies of haploid round spermatids and
      spermatogenic disomy rate may contribute to elevated risk of idiopathic male
      infertility.

PMID- 21094990
TI  - Urothelial cell platelet-activating factor production mediated by calcium
      independent phospholipase A2gamma.
AB  - OBJECTIVES: To determine the effect of phospholipase A(2) (PLA(2)) inhibitors on
      urothelial cell platelet-activating factor (PAF) production in response to
      tryptase stimulation. METHODS: Urothelial cells isolated from normal human
      ureters were immortalized with the human papillomavirus type 16E6E7 cell line
      (TEU-2 cells). PLA(2) activity in TEU-2 cells was measured using (16:0,
      [(3)H]18:1) plasmenylcholine and phosphatidylcholine substrates in the presence
      and absence of calcium. [(3)H]PAF production was measured in TEU-2 cells
      prelabeled with [(3)H] acetic acid. PAF-acetylhydrolase activity was measured by
      determining the amount of [(3)H] acetate hydrolyzed from [(3)H]PAF incubated with
      TEU-2 cellular protein. Adherence of human polymorphonuclear leukocyte (PMN) to
      TEU-2 cells was assessed by measuring myeloperoxidase activity in adherent PMNs
      after incubation with TEU-2 cells. RESULTS: Most PLA(2) activity measured in TEU
      2 cells was determined to be membrane-associated, calcium-independent PLA(2) and
      selective for plasmenylcholine substrate. Stimulation of TEU-2 cells with
      tryptase results in increased production of PAF and increased PMN adherence that
      were inhibited completely by pretreatment with the membrane-associated, calcium
      independent PLA(2)gamma-selective inhibitor (R)-bromoenol lactone. Pretreatment
      with the cytosolic PLA(2) inhibitor methyl arachidonyl fluorophosphonate resulted
      in potentiation of tryptase-stimulated PAF production and PMN adherence to TEU-2
      cells that is a result of PAF-acetylhydrolase inhibition. CONCLUSIONS: Tryptase
      stimulation of TEU-2 cells results in activation of membrane-associated, calcium
      independent PLA(2)gamma, leading to an increase in PAF production and increased
      PMN adherence. Inhibition of TEU-2 cell PAF-acetylhydrolase activity with methyl
      arachidonyl fluorophosphonate potentiated tryptase-stimulated PAF production and
      PMN adherence.

PMID- 21094991
TI  - Tolerance of bacteriuria after urinary diversion is linked to antimicrobial
      peptide activity.
AB  - OBJECTIVES: To compare the cationic antimicrobial peptide gene expression
      profiles and urinary cationic antimicrobial activities of patients after urinary
      diversion according to their urinary tract infection (UTI) status. Ileal conduit
      urinary diversion joins the bacterial-tolerant ileal epithelium and intolerant
      urothelium. After this procedure, one quarter of patients develop repeated
      symptomatic UTIs. Such development might reflect the altered innate immune
      mechanisms centered on epithelial expression and urinary activity of cationic
      antimicrobial peptides, such as defensins. METHODS: Ileal and ureteral biopsy
      specimens from ileal conduit subjects with (n = 18) and without (n = 18)
      recurrent symptomatic UTIs were assessed for cationic antimicrobial peptide gene
      expression using quantitative reverse transcriptase polymerase chain reaction.
      Overnight urine collections were analyzed for antimicrobial activity against a
      laboratory Escherichia coli strain, and infecting organisms were isolated from
      individual subjects. RESULTS: Overall, the ureteral epithelium showed increased
      expression of human alpha-defensin 5 and decreased expression of the human beta
      defensin 1 after urinary diversion (P < .05). No significant changes were seen
      for the ileal epithelium. The expression levels of both defensins also did not
      differ significantly according to UTI status. Urinary cationic activity against
      infecting bacterial isolates from the individual subjects was significantly
      greater in those with symptomatic UTI (P < .001), and the activities against the
      laboratory E. coli strain were similar. CONCLUSIONS: The changes in the human
      beta-defensin 1 and human alpha-defensin 5 expression profiles and the link
      between symptomatic infection and high urinary antimicrobial activity suggest
      that innate mechanisms play significant roles in balancing bacterial tolerance
      and killing after ileal conduit urinary diversion. Future work needs to determine
      whether these changes can be therapeutically modulated to benefit the patients.

PMID- 21094992
TI  - The effects of type 2 diabetes and hypertension on changes in serum prostate
      specific antigen levels: results from the Olmsted County study.
AB  - OBJECTIVE: Men with type 2 diabetes have lower concomitant prostate-specific
      antigen (PSA) levels; however, the influence of metabolic conditions on PSA
      changes over time remains unknown. Therefore, the goal of this study was to
      assess associations between type 2 diabetes and hypertension and changes in serum
      PSA levels. METHODS: In 1990, a randomly selected cohort of Caucasian men, ages
      40-79, from Olmsted County, MN completed questionnaires ascertaining demographic
      characteristics, current medical conditions and medications biennially, with 633
      men undergoing blood draws. Men with a physician diagnosis of diabetes or
      hypertension at baseline, or who reported using medications to treat these
      conditions prior to baseline were considered exposed. Men with at least two serum
      PSA measurements (n = 569) were included in this analysis. Linear mixed models
      were used to estimate the annual percent change in serum PSA levels associated
      with diabetes and hypertension, adjusting for baseline age. RESULTS: The overall
      mean change in serum PSA levels was 3.6% per year and increased with age (P =
      .009). Men with diabetes experienced less annual change in serum PSA levels
      (1.1%) than did non-diabetic men (3.7%), adjusting for age (P = .02). Age
      adjusted change in serum PSA levels differed little by hypertension status (3.7%
      vs. 3.6%; P = .49). CONCLUSIONS: Our results suggest that Caucasian men with type
      2 diabetes experience smaller increases in serum PSA levels as they age compared
      to men without diabetes. Additional research is needed to elucidate whether this
      difference results in a relatively lower incidence of prostate cancer or less
      cancer detection among diabetic men.

PMID- 21094993
TI  - Diffuse large B-cell lymphoma as presenting feature of Zap-70 deficiency.

PMID- 21094994
TI  - Sex differences in asthma during the first 8 years of life: the Prevention and
      Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study.

PMID- 21094995
TI  - Differences in the allergenicity of 6 different kiwifruit cultivars analyzed by
      prick-to-prick testing, open food challenges, and ELISA.

PMID- 21094996
TI  - From porcelain-fused-to-metal to zirconia: clinical and experimental
      considerations.
AB  - OBJECTIVE: The interest of dental research in metal-free restorations has been
      rising in the last 20 years following the introduction of innovative all-ceramic
      materials in the daily practice. In particular, high strength ceramics and
      related CAD/CAM techniques have widely increased the clinical indications of
      metal-free prostheses, showing more favourable mechanical characteristics
      compared to the early ceramic materials. The purpose of the present paper is
      providing a brief review on the all-ceramic dental materials, evaluating pros and
      cons in the light of the most recent scientific results and of the authors'
      clinical experience. MATERIALS: A structured review of the literature was given
      on the basis of medical and engineering papers published in the last decades on
      the use of dental ceramics and zirconia in particular. The experimental and
      clinical findings of the most relevant researches were reported. RESULTS:
      Zirconia is one of the most promising restorative materials, because it yields
      very favourable mechanical properties and reasonable esthetic. Several in vitro
      and in vivo investigations reported suitable strength and mechanical performances
      of zirconia, compatible with clinical serviceability as a framework material for
      both single crowns and short-span fixed partial dentures. However, clinical
      results are not comparable, at the moment, with conventional metal-ceramic
      restorations, neither is there sufficient long-term data for validating the
      clinical potential of zirconia in the long run. SIGNIFICANCE: The use of zirconia
      frameworks for long-span fixed partial dentures or for implant-supported
      restorations is currently under evaluation and further in vivo, long-term
      clinical studies will be needed to provide scientific evidence for drawing solid
      guidelines.

PMID- 21094997
TI  - Glomerular filtration rate, proteinuria, and the incidence and consequences of
      acute kidney injury: a cohort study.
AB  - BACKGROUND: Low values of estimated glomerular filtration rate (eGFR) predispose
      to acute kidney injury, and proteinuria is a marker of kidney disease. We aimed
      to investigate how eGFR and proteinuria jointly modified the risks of acute
      kidney injury and subsequent adverse clinical outcomes. METHODS: We did a cohort
      study of 920,985 adults residing in Alberta, Canada, between 2002 and 2007.
      Participants not needing chronic dialysis at baseline and with at least one
      outpatient measurement of both serum creatinine concentration and proteinuria
      (urine dipstick or albumin-creatinine ratio) were included. We assessed hospital
      admission with acute kidney injury with validated administrative codes; other
      outcomes were all-cause mortality and a composite renal outcome of end-stage
      renal disease or doubling of serum creatinine concentration. FINDINGS: During
      median follow-up of 35 months (range 0-59 months), 6520 (0.7%) participants were
      admitted with acute kidney injury. In those with eGFR 60 mL/min per 1.73 m(2) or
      greater, the adjusted risk of admission with this disorder was about 4 times
      higher in those with heavy proteinuria measured by dipstick (rate ratio 4.4 vs no
      proteinuria, 95% CI 3.7-5.2). The adjusted rates of admission with acute kidney
      injury and kidney injury needing dialysis remained high in participants with
      heavy dipstick proteinuria for all values of eGFR. The adjusted rates of death
      and the composite renal outcome were also high in participants admitted with
      acute kidney injury, although the rise associated with this injury was attenuated
      in those with low baseline eGFR and heavy proteinuria. INTERPRETATION: These
      findings suggest that information on proteinuria and eGFR should be used together
      when identifying people at risk of acute kidney injury, and that an episode of
      acute kidney injury provides further long-term prognostic information in addition
      to eGFR and proteinuria. FUNDING: The study was funded by an interdisciplinary
      team grant from Alberta Heritage Foundation for Medical Research.

PMID- 21094998
TI  - Proteinuria and risk of acute kidney injury.

PMID- 21094999
TI  - Sex-specific biochemical and histological differences in gonads of sea urchins
      (Psammechinus miliaris) and their response to phenanthrene exposure.
AB  - Female and male individuals of the same species often differ with respect to
      their susceptibility to toxicant stress. In the present study, sea urchins
      (Psammechinus miliaris) of both sexes were exposed to high (150 MUg L-1) and
      environmentally relevant (5 MUg L-1) concentrations of phenanthrene over 10 days.
      While food intake was significantly decreased following exposure to 150 MUg L-1
      phenanthrene, histological indices (lipofuscin accumulation, fibrosis, oocyte
      atresia), energetic status (energy charge, sum adenylates, AMP/ATP ratio) as well
      as ascorbate levels in the gonads showed either little or no effect upon
      phenanthrene exposure. However, most parameters (vitamin C, energy charge, sum
      adenylates, AMP/ATP ratio, ATP and ADP concentrations, lipofuscin content,
      fibrosis) significantly differed between male and female animals. This study
      illustrates the difficulties to identify toxic injury in reproductive tissue as
      it may be superimposed by gametogenesis and spawning of gametes.

PMID- 21095000
TI  - High-throughput generation of hydrogel microbeads with varying elasticity for
      cell encapsulation.
AB  - Elasticity of cellular microenvironments strongly influences cell motility,
      phagocytosis, growth and differentiation. Currently, the relationship between the
      cell behaviour and matrix stiffness is being studied for cells seeded on planar
      substrates, however in three-dimensional (3D) microenvironments cells may
      experience mechanical signalling that is distinct from that on a two-dimensional
      matrix. We report a microfluidic approach for high-throughput generation of 3D
      microenvironments with different elasticity for studies of cell fate. The
      generation of agarose microgels with different elastic moduli was achieved by (i)
      introducing into a microfluidic droplet generator two streams of agarose
      solutions, one with a high concentration of agarose and the other one with a low
      concentration of agarose, at varying relative volumetric flow rate ratios of the
      two streams, and (ii) on-chip gelation of the precursor droplets. At 37 degreesC,
      the method enabled a approximately 35-fold variation of the shear elastic modulus
      of the agarose gels. The application of the method was demonstrated by
      encapsulating two mouse embryonic stem cell lines within the agarose microgels.
      This work establishes a foundation for the high-throughput generation of
      combinatorial microenvironments with different mechanical properties for cell
      studies.

PMID- 21095002
TI  - Exploring chronic myeloid leukemia patients' reasons for not adhering to the oral
      anticancer drug imatinib as prescribed.
AB  - Nonadherence has been shown to be frequent amongst chronic myeloid leukemia (CML)
      patients prescribed imatinib, which results in reduced clinical response and
      increased healthcare costs. However, little is known about the reasons why CML
      patients frequently do not take their imatinib as prescribed. The current study
      explored CML patients' experience of taking, or not taking, imatinib therapy
      through in-depth interviews with twenty-one patients. Their adherence had been
      previously measured using a medication events monitoring device. The interviews
      were recorded, transcribed and analysed in accordance with established
      techniques. Patients revealed a variety of reasons for their nonadherence. Major
      themes that emerged from the data were the intentional and unintentional reasons
      for nonadherence. Furthermore, as a result of information received from health
      care professionals, several patients felt inappropriately reassured that their
      nonadherence would not have a detrimental effect on their clinical response.
      Factors that seemed to favour adherence were finding ways to deal with side
      effects and using prompts as reminders to take the medicine. This study forms a
      basis on which to build future adherence research and may help to develop
      interventions designed to ensure that patients with CML and other cancers adhere
      optimally to their oral drugs treatment.

PMID- 21095001
TI  - D2-40/podoplanin expression in the human placenta.
AB  - Placental tissue expresses many lymphatic markers. The current study was
      undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was
      expressed in the human placenta, and how it is altered developmentally and
      pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas
      from normotensive pregnancies at different gestational ages and in placentas from
      women with clinically defined preeclampsia. D2-40 expression in systemic
      lymphatic vessel endothelium served as a positive control. Protein expression for
      D2-40, VEGFR-3, and beta-actin was determined by Western blot in placentas from
      normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that
      D2-40/podoplanin was strongly expressed in the placenta, mainly as a network
      plexus pattern in the villous stroma throughout gestation. CD31 was limited to
      villous core fetal vessel endothelium and VEGFR-3 was found in both villous core
      fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was
      significantly decreased, and VEGFR-3 significantly increased in preeclamptic
      placental tissues compared to normotensive placental controls. Placental villous
      stroma is a reticular-like structure, and the localization of D2-40 to the stroma
      suggests that a lymphatic-like conductive network may exist in the human
      placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is
      known regarding biological functions of sialylated glycoproteins within the
      placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during
      placenta development and reduced D2-40/podoplanin expression in preeclamptic
      placenta may contribute to altered interstitial fluid homeostasis and impaired
      angiogenesis in this pregnancy disorder.

PMID- 21095003
TI  - Toxicological responses of Cyprinus carpio after exposure to a commercial
      herbicide containing imazethapyr and imazapic.
AB  - Cyprinus carpio was exposed to imazethapyr and imazapic at laboratory and at
      field conditions. The laboratory experiment was carried out for 7 days and at
      rice field for 7, 30 and 90 days. Oxidative stress parameters and antioxidant
      profile were studied as well as metabolic parameters. After 7 days, brain AChE
      activity increases in laboratory and field, but in muscle, reduction was observed
      only in laboratory. At the same period, brain and muscle TBARS and liver CAT
      increase in the laboratory. Metabolic parameters showed changes in both
      conditions and exposure periods. After 30 days in rice field, brain AChE activity
      decreases and in muscle it was enhanced. After 90 days in field, only muscle AChE
      activity was reduced. The disorders in oxidative stress parameters and metabolism
      remained, indicating mainly a protein catabolism. This study pointed out short-
      and long-term effects of rice herbicides at environmentally relevant
      concentrations on toxicological parameters in tissues of C. carpio.

PMID- 21095005
TI  - Comparison of the 2000 and 2005 spatial distributions of heavy metals in wild
      mussels from the North-Atlantic Spanish coast.
AB  - Spatial distributions of Cd, Cu, Hg, Pb and Zn in Mytilus galloprovincialis in 41
      sampling sites in the North-Atlantic Spanish coast were monitored in 2000 and
      2005 to assess the coastal environmental pollution. A pool of mussel soft tissue
      was prepared using 50 or more individuals representing the available size range.
      Samples were grounded, homogenised and quantified by atomic absorption
      spectrometry. Quality of the chemical analyses was assessed by participation in
      periodic interlaboratory exercises. Univariate and multivariate statistical
      studies, Principal Components Analysis and Procrustes rotation (a technique
      intended to compare several data spaces) were carried out. Some decreasing trends
      were observed for the concentrations throughout the 2000-2005 period, mainly for
      Hg and Pb. In general, the Northern area showed higher median concentrations
      (e.g., 3.79 and 4.28 mg Pb/kg dry weight, and 0.160 and 0.191 mg Hg/kg dry
      weight, for 2000 and 2005, respectively) than the Atlantic ones (e.g., 1.47 and
      1.44 mg Pb/kg dry weight, and 0.097 and 0.084 mgHg/kg dry weight, for 2000 and
      2005, respectively). Nevertheless, some Atlantic sampling points, located far
      from human inputs (cities, industries, rivers, etc.) exhibited high
      concentrations of Cd, which was attributed to the influence of the natural
      upwelling processes which occur annually in that geographical region.

PMID- 21095004
TI  - Effects of pulp and paper mill effluent extracts on liver anaerobic and aerobic
      metabolic enzymes in rainbow trout.
AB  - This study investigates whether pulse exposure to Chilean pulp and paper mill
      effluent solid phase extracted (SPE) extracts via intraperitoneal injection (IP),
      would result in changes in the activities of the respiratory metabolic enzymes
      citrate synthase (CS) and lactate dehydrogenase (LDH) in rainbow trout livers. It
      also investigated if an alteration in liver metabolic capacity influenced the
      liver detoxification processes and estrogenic effects previously reported.
      Besides, a comparison of those enzymatic activities with fish IP injected with
      SPE extracts of two model effluents coming from industries that process 100%
      different type of feedstock (softwood, SW and hardwood, HW) was also evaluated.
      An initial induction of the anaerobic metabolism (increase in LDH enzymatic
      activity) was detected in all Chilean pulp mill effluent extracts evaluated,
      contrary to the initial unaltered aerobic metabolism (CS enzymatic activity)
      observed. A compensatory relationship in energy metabolism (Pasteur effect) was
      observed when comparing both enzymatic activities of fish exposed to those
      effluent extracts. LDH and CS activities observed in fish injected with Chilean
      extracts seem to be related to the effects observed in fish injected with SW
      extracts. This study showed that intraperitoneal injection of pulp and paper mill
      effluent extracts affected the anaerobic and aerobic metabolic capacities in
      rainbow trout livers, but this metabolic alteration did not affect detoxification
      capability or estrogenic effect previously reported.

PMID- 21095006
TI  - Daphnia response to biotic stress is modified by PCBs.
AB  - The aim of this study was to examine the influence of xenobiotics (PCBs) on the
      responses of Daphnia to biotic factors such as the presence of a predator (fish
      kairomone) or filamentous cyanobacteria. Both behaviour (depth selection) and
      life history (body size at first reproduction and fecundity) were affected by
      these stressors. Though there was no direct effect of PCBs, their influence
      resulted in disruption of the "natural" reaction to the presence of fish or
      cyanobacteria, leading to inadequate responses of Daphnia to these biotic
      threats. Examined clones of Daphnia showed significant diversity in their
      reaction to these stress factors, which was greater than that between Daphnia
      clones exposed to different environmental conditions. PCB pollution may change
      the frequency of Daphnia clones in favour of those whose responses to biotic
      stress are similar in both the absence and presence of these toxic chemicals.

PMID- 21095007
TI  - Latex-allergic patients sensitized to the major allergen hevein and hevein-like
      domains of class I chitinases show no increased frequency of latex-associated
      plant food allergy.
AB  - Allergies to certain fruits such as banana, avocado, chestnut and kiwi are
      described in 30-70% of latex-allergic patients. This association is attributed to
      the cross-reactivity between the major latex allergen hevein and hevein-like
      domains (HLDs) from fruit class I chitinases. We aimed to assess the extent of
      cross-reactivity between hevein and HLDs using sera from latex-allergic patients
      with and without plant food allergy. Hevein and HLDs of latex, banana, and
      avocado chitinases were expressed in Escherichia coli as fusion proteins with the
      maltose-binding protein and purified by affinity chromatography. IgE binding to
      these proteins was studied in sera from 59 latex-allergic patients and 20 banana
      allergic patients without latex allergy by ELISA and ELISA inhibition.
      Additionally, 16,408 allergic patients' sera were tested for IgE binding to
      hevein, latex chitinase, and wheat germ agglutinin using an allergen microarray.
      Hevein-specific IgE was detected in 34/59 (58%) latex-allergic patients' sera.
      HLDs of latex, banana, and avocado chitinases were recognized by 21 (36%), 20
      (34%), and 9 (15%) sera, respectively. In contrast, only one of 20 banana
      allergic patients without latex allergy was sensitized to chitinase HLDs. In most
      tested latex-allergic patients' sera, IgE binding to hevein was only partially
      reduced by preincubation with HLDs. Among hevein-sensitized, latex-allergic
      patients, the percentage of plant food allergy (15/34 = 44%) was equal to latex
      allergic patients without hevein sensitization (11/25 = 44%). In the general
      allergic population, 230 of 16,408 sera (1.4%) reacted to hevein and/or a hevein
      like allergen. Of these, 128 sera showed an isolated sensitization to hevein,
      whereas only 17 bound to latex chitinase or wheat germ agglutinin without hevein
      sensitization. In conclusion, the IgE response to HLDs is elicited by hevein as
      sensitizing allergen in most cases. Despite considerable cross-reactivity between
      these allergens, no correlation between latex-associated plant food allergy and
      sensitization to hevein or HLDs was found.

PMID- 21095008
TI  - IL-10 inhibits the starvation induced autophagy in macrophages via class I
      phosphatidylinositol 3-kinase (PI3K) pathway.
AB  - Autophagy is an important process which maintains cellular homeostasis under
      stressful conditions such as starvation and pathogenic invasion. Previous
      observations have indicated that several cytokines are important regulators of
      the autophagic process. Among the various cytokines, IL-10 has a unique property
      which functions to suppress overall immunity. However, the functional role of IL
      10 during the autophagic process has not been studied. In this study, we examined
      the effect of IL-10 during starvation induced autophagy of murine macrophages
      (J774). The results clearly indicated that IL-10 and IL-10 receptor signaling
      inhibits autophagy induction of murine macrophage. Further experiments revealed
      that IL-10 activates the class I phosphatidylinositol 3-kinase (PI3K) pathway,
      which results in the phosphorylation of p70S6K through the activation of Akt and
      a mammalian target of the rapamycin complex 1 (mTORC 1). These results will
      advance our understanding of the physiological function of IL-10 during the
      autophagic process of macrophage.

PMID- 21095009
TI  - Genome-wide association studies reveal genetic variants in CTNND2 for high myopia
      in Singapore Chinese.
AB  - OBJECTIVE: To determine susceptibility genes for high myopia in Singaporean
      Chinese. DESIGN: A meta-analysis of 2 genome-wide association (GWA) datasets in
      Chinese and a follow-up replication cohort in Japanese. PARTICIPANTS AND
      CONTROLS: Two independent datasets of Singaporean Chinese individuals aged 10 to
      12 years (Singapore Cohort Study of the Risk factors for Myopia [SCORM]: cases =
      65, controls = 238) and more than 21 years (Singapore Prospective Study Program
      [SP2]: cases = 222, controls = 435) for GWA studies, and a Japanese dataset aged
      more than 20 years (cases = 959, controls = 2128) for replication. METHODS:
      Genomic DNA samples from SCORM and SP2 were genotyped using various Illumina
      Beadarray platforms (>HumanHap 500). Single-locus association tests were
      conducted for each dataset with meta-analysis using pooled z-scores. The top
      ranked genetic markers were examined for replication in the Japanese dataset.
      Fisher P was calculated for the combined analysis of all 3 cohorts. MAIN OUTCOME
      MEASURES: High myopia, defined by spherical equivalent (SE) <= -6.00 diopters
      (D); controls defined by SE between -0.50 and +1.00 D. RESULTS: Two SNPs
      (rs12716080 and rs6885224) in the gene CTNND2 on chromosome 5p15 ranked top in
      the meta-analysis of our Chinese datasets (meta P = 1.14 * 10(-5) and meta P =
      1.51 * 10(-5), respectively) with strong supporting evidence in each individual
      dataset analysis (max P = 1.85 * 10(-4) in SCORM: max P = 8.8 * 10(-3) in SP2).
      Evidence of replication was observed in the Japanese dataset for rs6885224 (P =
      0.035, meta P of 3 datasets: 7.84 * 10(-6)). CONCLUSIONS: This study identified a
      strong association of CTNND2 for high myopia in Asian datasets. The CTNND2 gene
      maps to a known high myopia linkage region on chromosome 5p15.

PMID- 21095010
TI  - Vitreomacular interface in typical exudative age-related macular degeneration and
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: To investigate the association in Japanese between posterior vitreous
      attachment and the pathologies of typical age-related macular degeneration (AMD)
      and polypoidal choroidal vasculopathy (PCV), 2 major forms of exudative AMD.
      DESIGN: Retrospective observational case series. PARTICIPANTS: A total of 378
      eyes from 302 subjects (132 with typical AMD, 126 with PCV, 120 controls) from
      the University of Tokyo Hospital. METHODS: Posterior vitreous detachment (PVD)
      and vitreomacular adhesion (VMA) were investigated by B-mode ultrasonography and
      spectral-domain optical coherence tomography (SD-OCT), respectively. The greatest
      linear dimension (GLD) of initial photodynamic therapy (PDT) in a subset of the
      patients (n=92) receiving PDT was also investigated. MAIN OUTCOME MEASURES:
      Number of eyes with complete PVD and with VMA. The GLD of initial PDT. RESULTS:
      In typical AMD eyes, the frequency of complete PVD was significantly lower (63
      [56.8%] of 111 eyes) than in the controls (52 [70.3%] of 74 eyes, risk ratio [RR]
      0.76, P=0.021) and the frequency of VMA tended to be higher (14/115 [12.2%] in
      typical AMD eyes and 6/86 [7.0%] in the controls, RR 2.15, P=0.099). The
      frequency of complete PVD [77 [63.1%] of the 122 eyes] and VMA (9/108 [8.3%]) in
      PCV eyes was the same as the controls (RR 0.91, P=0.415 and RR 1.29, P=0.615). In
      patients with unilateral exudative AMD, the frequency of complete PVD was lower
      in typical AMD eyes than in fellow eyes (odds ratio [OR] 0.111, P=0.026) and VMA
      was observed in 7 (17.5%) and 3 (7.5%) typical AMD and fellow eyes, respectively
      (OR 2.33, P=0.34), whereas in PCV eyes, the frequency of complete PVD was higher
      (OR 8.00, P=0.045) and the frequency of VMA was the same as in the fellow eyes
      (OR 0.80, P=1.00). The GLD of the eyes without complete PVD or with VMA was
      significantly larger than that in the eyes with complete PVD in typical AMD eyes
      (P=0.042) and the same as that in the eyes with complete PVD in PCV eyes
      (P=0.67). CONCLUSIONS: There is an association between posterior vitreous
      attachment and typical AMD. However, this association is not evident in PCV.

PMID- 21095011
TI  - Two-to-three-year-old children's interactions with peers in child-care centres:
      Effects of spatial distance to caregivers.
AB  - In child-care centres, the influence of caregivers on the development of peer
      interactions seems ambivalent and mixed results are reported in the literature.
      Adopting an environmental approach, we examined the effects of the caregivers'
      spatial proximity on children's social behaviour. The study was carried out with
      175 children (18-40 months) in 12 child-care-centre groups. Children's behaviours
      were observed during free plays, and both children and caregivers' locations were
      recorded. When peers were nearby, children's social behaviours were compared when
      they were in the immediate proximity (within 2m) and out of the immediate
      proximity of a caregiver. Results show that in the latter situation children
      spend substantially more time addressing social overture to peers and interacting
      with them; positive interactions with peers show a particularly marked
      difference. This pattern of results is exhibited by the greater part of the
      children. Whatever the child-care-centre group, the age subgroup or the gender
      considered similar results are found. Results also demonstrate that when children
      are in the immediate proximity of caregivers they are socially oriented towards
      the attractive adult partners rather than towards peers.

PMID- 21095012
TI  - Engulfment of spermatozoa by cumulus cells and the role of CD36.
AB  - The function of cumulus cells after sperm penetration is not well understood. The
      present study examined the phagocytic action of cumulus cells on sperm after
      dispersion of cumulus-oocyte complexes. In a co-incubation system of cauda sperm
      and cumulus cells, the sperm heads were beginning to vanish after 2.5h and 77%+/
      1.34 of sperm heads had disappeared at 30 h. Most of the sperm heads were
      engulfed by cumulus cells. Immunofluorescent studies showed that cumulus cells
      were expressing the CD36 molecule, and sperm were exposing phosphatidylserine
      (PS). Anti-CD36 antibody and annexin V inhibited the engulfment of sperm by
      cumulus cells by 26.0% and 40.5%, respectively. These results suggested that the
      cumulus cells recognized the PS molecules on sperm via CD36 and this molecular
      interaction possibly triggered the phagocytosis of sperm by cumulus cells. These
      results suggest that cumulus cells might play a role in inhibiting undesired
      immune reactions induced by sperm antigens.

PMID- 21095013
TI  - Predicting violence using structured professional judgment in patients with
      different mental and behavioral disorders.
AB  - We examined whether a leading instrument for the prediction of future violence in
      those with a mental disorder. The Historical, Clinical, Risk Management-20 (HCR
      20) was equally effective across a wide range of mental health diagnoses. Records
      at the time of discharge from secure psychiatric services were used to score the
      HCR-20 risk assessment scheme. Patients were stratified according to whether they
      had received a particular mental health diagnosis. Reconvictions within 2 years
      of discharge were obtained from official sources and classified as to whether the
      offence was violent or not. Those with a diagnosis of either personality disorder
      or substance abuse were most likely to be reconvicted, whilst those with either a
      diagnosis of schizophrenia or mental retardation were the least likely. The HCR
      20 was a statistically significant predictor of future violence in all groups;
      however, it returned only weak effects for the personality disordered group, but
      strong effects for those in the schizophrenia or mental retardation group. The
      HCR-20 risk assessment scheme is effective across a wide range of diagnoses.
      Nevertheless, the prediction of future events appears more difficult in those
      disorders characterized by impulsive behaviors and further research efforts are
      needed to understand how such prediction can be improved.

PMID- 21095014
TI  - Concurrent validity of the Health of the Nation Outcome Scales compared with a
      patient-derived measure, the Symptom Checklist-90-Revised in out-patient clinics.
AB  - The psychometric properties of the Health of the Nation Outcome Scales (HoNOS)
      have been questioned. The present study examined the concurrent validity of the
      HoNOS against a patient-derived measure (the Symptom Checklist-90-R (SCL-90-R))
      in out-patients. This relationship has previously only been investigated in in
      patients. The study considered newly admitted patients, and only those with a
      complete data set were analyzed (N=118). Internal consistency (Cronbach's alpha)
      and effect sizes were calculated on pre- and post-treatment data. Concurrent
      validity was assessed using correlation (Spearman's rho) as well as agreement
      (kappa) on reliable and clinically significant change (RCSC). The internal
      consistencies associated with the SCL-90-R were satisfactory, a property shared
      only by the HoNOS sum score. The pre- to post-treatment changes in both
      instruments corresponded to medium to large effect sizes and were comparable in
      size. However, the correlations between the two were low, as was their agreement.
      This suggests that the HoNOS and the SCL-90-R measure somewhat different
      phenomena. The findings shed doubt on whether the patient-derived measures should
      be regarded as the "gold standard". The instruments seem to complement each
      other.

PMID- 21095015
TI  - Use of antipsychotics - an analysis of lifetime treatment in 66 patients with
      psychoses.
AB  - Only a minority of patients treated with antipsychotics in clinical studies
      continue their treatments throughout a longer study period. Few studies address
      this issue from a lifetime perspective. In this naturalistic study, we aimed at
      analysing the prescription pattern of antipsychotic drugs among a sample of
      Swedish patients with a diagnosis of psychotic illness, from the first contact
      with psychiatry (typically between 1973 and 1997) until the last written note in
      the case history documents. A retrospective descriptive analysis was performed of
      all case history data of 66 patients diagnosed with schizophrenia or related
      psychotic disorders. Patients with schizophrenia were prescribed antipsychotic
      medication more than 90% of the time. Each patient generally had been prescribed
      several (up to 16) different antipsychotic drugs and a quarter of the patients
      had been prescribed two or more antipsychotics for a third of their prescription
      time. Patients with psychosis were exposed to a cumulatively growing number of
      antipsychotics. Various factors, including clinician and patient expectations,
      and specific strengths and limitations of available antipsychotics may account
      for frequent medication changes over time.

PMID- 21095016
TI  - Association of DRD2 and ANKK1 polymorphisms with prolactin increase in olanzapine
      treated women.
AB  - Dopamine D2 receptors, encoded by DRD2, play a role in regulating serum prolactin
      concentration. Single nucleotide polymorphisms (SNPs), rs2734842(C), rs6275(T),
      and rs6279(C) located within DRD2, have been shown to be associated with
      prolactin increase in olanzapine/fluoxetine combination (OFC)-treated women. The
      present analyses seek to replicate these results and test other SNPs in DRD2 and
      neighboring gene ANKK1 for associations with prolactin increase in women, using
      data from 3 pooled studies of olanzapine, and 2 previously examined studies OFC.
      An ANCOVA was used to test whether change from baseline in the natural log of
      prolactin concentration (ln[prolactin]) was associated with SNPs in the pooled
      olanzapine studies. A meta-analysis was also performed using the inverse chi
      square method, pooling p-values from the 2 previously examined studies and the 3
      olanzapine studies. Negative strand alleles rs2734842(C), rs6275(T), and
      rs6279(C) were significantly associated with increased prolactin in olanzapine
      treated women, replicating previous results. These SNPs also showed moderate
      association with increased prolactin in olanzapine-treated and OFC-treated women
      in the meta-analysis, as did rs4938016, rs2734848, rs2734841, rs1124493, and
      rs1076562. Five of these SNPs fall in or are adjacent to an LD block spanning
      DRD2 intron 7, exon 7, 5' untranslated region and ANKK1. CLINICAL TRIAL
      REGISTRATION: www.clinicaltrial.gov.

PMID- 21095017
TI  - Personality development characteristics of women with anorexia nervosa, their
      healthy siblings and healthy controls: What prevents and what relates to
      psychopathology?
AB  - This exploratory study assessed attachment and personality in anorexic women, non
      affected siblings, and healthy controls, examining correlations with
      psychopathology. Thirty-eight anorexic subjects (31 females), thirty-one siblings
      (22 females), and fifty controls (35 females) participated. Personality
      development characteristics were assessed using the Attachment Style
      Questionnaire (ASQ), Temperament and Character Inventory (TCI), Eating Disorders
      Inventory (EDI-2), Symptom Checklist-90 (SCL-90), and other inventories for
      clinical assessment of EDs. Both anorexic probands and their siblings described
      lower maternal care and higher maternal overprotection than did controls. Healthy
      siblings were more similar to controls, but had lower scores than either controls
      or affected siblings on preoccupation with relationships (P<0.005) and higher
      scores than controls on self-transcendence (P<0.015) and obsessive-compulsive
      traits (P<0.025). Logistic regression indicated that need for approval,
      persistence, resourcefulness, self-transcendence, state anger, pursuit of
      thinness, interpersonal distrust, social insecurity, and binge eating
      differentiated anorexic probands from siblings. The need for approval was related
      to several psychopathological characteristics. Low preoccupation with
      relationships, low need for approval, and high self-transcendence may have
      protected siblings from family and environmental stressors. High need for
      approval was independently related to psychopathological traits in anorexic
      siblings. Implications for prevention and treatment are discussed.

PMID- 21095018
TI  - Associations of impaired behaviors with elevated plasma chemokines in autism
      spectrum disorders.
AB  - A role for immune dysfunction has been suggested in autism spectrum disorders
      (ASD). Elevated levels of chemokines have been detected in the brain and CSF of
      individuals with ASD but, to date, no study has examined chemokine levels in the
      plasma of children with this disorder. In the current study, we determined
      whether there were differential profiles of chemokines in the plasma of children
      with ASD compared to age-matched typically developing controls and children with
      developmental disabilities other than ASD. Increased MCP-1, RANTES and eotaxin
      levels were observed in ASD children compared with both control groups (p<0.03),
      and increased chemokine production was associated with higher aberrant behavior
      scores and more impaired developmental and adaptive function.. Elevated MCP-1,
      RANTES and eotaxin in some ASD children and their association with more impaired
      behaviors may have etiological significance. Chemokines and their receptors might
      provide unique targets for future therapies in ASD.

PMID- 21095019
TI  - Intracranial hemorrhage causes a transmural myocardial infarction without the
      presence of coronary atherosclerosis.

PMID- 21095020
TI  - Chronic formoterol administration reduces cardiac mitochondrial protein synthesis
      and oxidative capacity in mice.

PMID- 21095021
TI  - Effects of simvastatin therapy on circulating adipocytokines in patients with
      hypercholesterolemia.

PMID- 21095022
TI  - Cigarette smoking and vascular conditions in elderly males: evidence from a
      community-based study.

PMID- 21095023
TI  - Relation between red blood cell distribution width and mortality after acute
      myocardial infarction.

PMID- 21095024
TI  - Association of coronary inflammation and angiotensin II with impaired
      microvascular reperfusion in patients with ST-segment elevation myocardial
      infarction.

PMID- 21095025
TI  - Prevalence of hyperuricemia and its association with antihypertensive treatment
      in hypertensive patients in Taiwan.
AB  - BACKGROUND: Hyperuricemia is thought to be associated with an increased risk of
      hypertension, impaired renal function and cardiovascular disease. Our aim is to
      study the prevalence of hyperuricemia and its association with antihypertensive
      treatment in Taiwanese hypertensive subjects. METHODS: We recruited 2145
      hypertensive subjects from 19 hospitals in four areas of Taiwan. We assessed the
      prevalence of hyperuricemia and determined the independent risk factors for
      raised serum uric acid level by multiple logistic regression analyses. RESULTS:
      Compared to the general population, hypertensive subjects in Taiwan had a higher
      prevalence (mean 35% in males, 43% in females) of hyperuricemia; this prevalence
      being 1.5- and 1.7-fold higher in males and females respectively. Uric acid
      levels; gout and prevalence of hyperuricemia were found to be highest in the
      younger age group (20-39 years) and no regional differences were noted. The most
      important risk factors for hyperuricemia were impaired renal function and
      diuretic use. Serum uric acid values correlated significantly with four quintiles
      of serum creatinine (p<0.0001) independent of diuretic use. Diuretic users had a
      significantly elevated serum uric acid and serum creatinine values than non
      users. Among the patients given diuretics, hyperuricemia occurred in 44% of those
      given thiazides, in 56% of those given loop diuretics, and in 57% of those given
      aldosterone receptor blockers. CONCLUSIONS: Diuretic usage and renal function
      status have a strong impact on the prevalence of hyperuricemia in Taiwanese
      hypertensive subjects. It is still unclear, however, whether diuretics induce
      renal failure through elevating serum uric acid levels.

PMID- 21095026
TI  - Renal dysfunction in syndrome Y.

PMID- 21095027
TI  - Titanium-nitride-oxide-coated bioactive stents: a novel evolution of stent
      technology.

PMID- 21095028
TI  - Co-treatment with azelinidipine and olmesartan inhibits advanced glycation end
      products (AGEs) elicited down-regulation of adiponectin mRNA levels in cultured
      adipocytes partly via its anti-oxidative property.

PMID- 21095029
TI  - Ibn Sina's treaties on pulsology.

PMID- 21095030
TI  - Upstream tirofiban reduces reperfusion cardiac arrhythmias in patients of acute
      ST-elevation myocardial infarction undergoing primary percutaneous coronary
      intervention.

PMID- 21095031
TI  - Temporal changes in diastolic function in heart failure patients with restrictive
      filling.

PMID- 21095033
TI  - Reporting of methodological features in observational studies of pre-harvest food
      safety.
AB  - Observational studies in pre-harvest food safety may be useful for identifying
      risk factors and for evaluating potential mitigation strategies to reduce
      foodborne pathogens. However, there are no structured reporting guidelines for
      these types of study designs in livestock species. Our objective was to evaluate
      the reporting of observational studies in the pre-harvest food safety literature
      using guidelines modified from the human healthcare literature. We identified 100
      pre-harvest food safety studies published between 1999 and 2009. Each study was
      evaluated independently by two reviewers using a structured checklist. Of the 38
      studies that explicitly stated the observational study design, 27 were described
      as cross-sectional studies, eight as case-control studies, and three as cohort
      studies. Study features reported in over 75% of the selected studies included:
      description of the geographic location of the studies, definitions and sources of
      data for outcomes, organizational level and source of data for independent
      variables, description of statistical methods and results, number of herds
      enrolled in the study and included in the analysis, and sources of study funding.
      However, other features were not consistently reported, including details related
      to eligibility criteria for groups (such as barn, room, or pen) and individuals,
      numbers of groups and individuals included in various stages of the study,
      identification of primary outcomes, the distinction between putative risk factors
      and confounding variables, the identification of a primary exposure variable, the
      referent level for evaluation of categorical variable associations, methods of
      controlling confounding variables and missing variables, model fit, details of
      subset analysis, demographic information at the sampling unit level, and
      generalizability of the study results. Improvement in reporting of observational
      studies of pre-harvest food safety will aid research readers and reviewers in
      interpreting and evaluating the results of such studies.

PMID- 21095034
TI  - Do expert patients get better treatment than others? Agency discrimination and
      statistical discrimination in obstetrics.
AB  - We address models that can explain why expert patients (obstetricians, midwives
      and doctors) are treated better than non-experts (mainly non-medical training).
      Models of statistical discrimination show that benevolent doctors treat expert
      patients better, since experts are better at communicating with the doctor.
      Agency theory suggests that doctors have an incentive to limit hospital costs by
      distorting information to non-expert patients, but not to expert patients. The
      hypotheses were tested on a large set of data, which contained information about
      the highest education of the parents, and detailed medical information about all
      births in Norway during the period 1967-2005 (Medical Birth Registry). The
      empirical analyses show that expert parents have a higher rate of Caesarean
      section than non-expert parents. The educational disparities were considerable 40
      years ago, but have become markedly less over time. The analyses provide support
      for statistical discrimination theory, though agency theory cannot be totally
      excluded.

PMID- 21095035
TI  - Microbial quality and nutritional aspects of Norwegian brand waters.
AB  - The microbiological quality of the five leading brands of Norwegian bottled still
      waters was investigated. All brands were free for the enteric indicator organisms
      and named pathogens whose absence is demanded in current quality directives. The
      relatively nutrient-poor agar R2A revealed large heterogeneous bacterial
      populations which grew slowly, or not at all, on clinical media specified for use
      in substrate-utilization approaches to identification. The main approach used for
      identification was cultivation of microbes on R2A, followed by amplification and
      partial sequencing of 16S rDNA genes. The identity of the heterotrophic plate
      count of the brands differed significantly to that found in many other similar
      studies with respect to the dominating species. The bacterial flora was dominated
      by beta- and alphaproteobacteria most of which were psychrotolerant. Several
      brands contained Sphingomonas and large populations of Methylobacterium species
      which have been associated with a variety of opportunistic infections of
      immunocompromised hosts. Analysis of the isolated strains' nutritional
      capabilities using the Biolog GN2(r) system, gave in most instances low positive
      scores, and strain identifications using the system were generally inconclusive.
      Measures of assimilable organic carbon in the water revealed that some brands
      contained levels higher than those which have been associated with biological
      stability and restricted or no growth of heterotrophs in distribution systems.
      The relationship between assimilable organic carbon and R2A plate counts was
      significant and moderately positive for bottled waters. Assimilable organic
      carbon correlated strongly with the survival time of Escherichia coli when
      introduced into bottles as a contaminant. Those brands having high values (~100
      MUg/L) supported protracted survival, but not growth of E. coli, whereas E. coli
      quickly became nonculturable in brands with low values. Thus measures of
      assimilable organic carbon may have a particular value in predicting the survival
      of this and nutritionally similar species of hygienic relevance. Only small
      numbers of fungi were found. However, one isolate (Aureobasidium pullulans) has
      been associated with infections of humans.

PMID- 21095036
TI  - Viral load reduction improves activation and function of natural killer cells in
      patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: Natural killer (NK) cells play a major role in anti-viral
      immunity as first line defense and regulation of virus-specific T cell responses.
      This study aimed to investigate phenotype and function of NK cells in patients
      with chronic hepatitis B virus (HBV) infection and to study the effect of anti
      viral therapy. METHODS: Peripheral blood NK cells from 40 chronic HBV patients
      were compared to NK cells of 25 healthy controls. The effect of entecavir-induced
      viral load reduction on NK cell phenotype and function was investigated in 15
      chronic HBV patients. RESULTS: NK cell numbers and subset distribution did not
      differ between HBV patients and normal subjects. In chronic HBV patients, the
      cytotoxic capacity was retained, but NK cell activation and subsequent IFNgamma
      and TNFalpha production, especially of the CD56(dim) subset, were strongly
      hampered. This functional dichotomy was paralleled by an altered activation
      state, elevated expression of NKG2A, and downregulated expression of CD16 and
      NKp30, which correlated with serum HBV-DNA load. Anti-viral therapy partially
      restored NK cell phenotype, as shown by NKG2A downregulation. Moreover, viral
      replication inhibition improved IFNgamma production as a result of an increased
      ability of CD56(dim) NK cells to become activated de novo. This improved NK cell
      activation and function which correlated with therapy-induced reduction in serum
      ALT levels, but not HBV-DNA load. CONCLUSIONS: The specific defect in CD56(dim)
      NK cell activation and the reduced capacity to produce anti-viral and Th1-skewing
      cytokines may play a role in HBV persistence. Restoration of this NK cell
      cytokine-producing capacity, as achieved by viral load reduction, could therefore
      contribute to definite clearance of the virus.

PMID- 21095037
TI  - Premature senescence induced by DNA demethylating agent (Decitabine) as
      therapeutic option for malignant pleural mesothelioma.
AB  - The drug-dependent induction of premature senescence in neoplastic cells is
      considered per se an important tumor suppressive mechanism. DNA demethylating
      agents recently introduced in clinical trials, such as 5-aza-cytidine
      (Decitabine) and its derivatives, have been extensively characterized in recent
      years as antiproliferative compounds that act through multiple mechanisms, which
      have not yet been fully clarified. We recently analyzed the introduction of
      Decitabine in therapy for malignant pleural mesothelioma (MPM) observing that,
      despite the ability to induce profound biological effects in MPM cells, the drug
      failed to generate a massive apoptotic response. Since one of the most intriguing
      aspects of DNA demethylating agents is the possibility to accelerate the
      senescent response of tumor cells, we investigated the hypothesis of Decitabine
      inducing, in vitro, the premature aging of MPM cells.

PMID- 21095038
TI  - IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA
      hypermethylation.
AB  - Insulin-like growth factor binding protein 7 (IGFBP7) was considered a tumor
      suppressor gene in lung cancer. However, the mechanism responsible for the
      downregulation of this gene has not yet been fully understood. In this study, we
      analyzed the epigenetic inactivation of IGFBP7 expression in human lung cancer.
      We found that 14 out of 16 lung cancer cell lines showed decreased expression of
      IGFBP7 compared to control cells by real-time RT-PCR, and 42 out of 90 patients
      (46.7%) with primary lung tumor exhibited negative staining of IGFBP7 by
      immunohistochemistry analysis. The IGFBP7 expression could be restored by
      demethylation agent 5-aza-2'-deoxycytidine (DAC) in 7 cancer cell lines.
      Methylation status of IGFBP7 was further evaluated by bisulfite sequencing (BS)
      and methylation-specific-PCR (MSP). It turned out that low expression of IGFBP7
      was associated with DNA methylation in lung cancer cell lines and in primary lung
      tumors (P=0.019). To explore the regulatory role of p53 on IGFBP7, we transfected
      a wild type p53 expression vector into lung cancer cell lines H1299, H2228, and
      H82. Forced expression of p53 increased IGFBP7 expression only in H82 harboring
      no IGFBP7 methylation, while transfection in combination with DAC induced the
      expression of IGFBP7 in H1299 and H2228, in which IGFBP7 was methylated.
      Additionally, treatment with p53 inducer adriamycin (ADR) alone or in combination
      with DAC increased the expression of IGFBP7 in the 3 cell lines. Our data suggest
      that IGFBP7 is inactivated in lung cancer by DNA hypermethylation in both lung
      cancer cell lines and primary lung tumors, and IGFBP7 might be regulated by p53
      in lung cancer cells.

PMID- 21095039
TI  - Prevalence and effectiveness of first-, second-, and third-line systemic therapy
      in a cohort of unselected patients with advanced non-small cell lung cancer.
AB  - Systemic therapy is the most relevant option for patients with advanced non-small
      cell lung cancer (NSCLC) and many receive therapies beyond first-line. Little is
      known on response, progression free survival (PFS) and overall survival (OS) and
      their prognostic factors after second- and third-line therapy in daily clinical
      practice. Between January 2003 and July 2007, 406 consecutive patients were
      included in this prospective observational study and followed up until August
      2010. At each treatment line the timing and kind of therapy, best response
      achieved, sites and time of progression were documented. Multiple logistic and
      Cox-regression models were used to analyse prognostic factors for achieving
      disease control (DC: response or disease stabilization), PFS and OS after
      different therapy lines. DC rate and median PFS decreased from 64% and 146 days,
      to 41% and 49 days, and to 39% and 51 days in response to first-, second- and
      third-line, respectively. A strong predictor for a worse outcome after second
      line was development of new metastases after first-line therapy (DC: OR=2.50; 95%
      CI: 1.30-4.83; p-value=0.006; PFS: HR=1.53; 95% CI: 1.13-2.06; p-value=0.005) or
      achieving no DC after first-line (OS: HR=1.41; 95% CI: 1.01-1.97; p-value=0.041).
      Achieving no DC after second-line was a strong negative predictor for all outcome
      measures after third-line therapy (DC: OR=5.10; 95% CI: 1.56-16.6; p-value=0.007;
      PFS: HR=2.00; 95% CI: 1.23-3.27; p-value=0.005; OS: HR=1.69; 95% CI: 1.02-2.79; p
      value=0.042). In conclusion, response in previous line and no involvement of new
      metastases after progression were relevant positive prognostic factors. However,
      further research is necessary to identify optimal therapy sequences.

PMID- 21095040
TI  - Pleiotropy, apparent stabilizing selection and uncovering fitness optima.
AB  - Evolutionary theory has emphasized that the evolution of single traits cannot be
      understood in isolation when pleiotropy is present. Widespread pleiotropy causes
      the appearance of stabilizing selection on metric traits owing to joint effects
      with fitness, and results in the genetic variation being concentrated in
      relatively few combinations of the measured traits. In this review, we show how
      trait combinations with high levels of genetic variation can be used to uncover
      fitness optima that are defined by apparent stabilizing selection. Defining
      fitness optima in this way could provide one avenue by which researchers can
      overcome the problem posed by measuring the myriad of traits that must influence
      fitness, or by measuring total fitness itself.

PMID- 21095041
TI  - Forced-air warming blowers: An evaluation of filtration adequacy and airborne
      contamination emissions in the operating room.
AB  - BACKGROUND: Forced-air warming (FAW) is widely used to prevent hypothermia during
      surgical procedures. The airflow from these blowers is often vented near the
      operative site and should be free of contaminants to minimize the risk of
      surgical site infection. Popular FAW blowers contain a 0.2-MUm rated intake
      filter to reduce these risks. However, there is little evidence that the
      efficiency of the intake filter is adequate to prevent airborne contamination
      emissions or protect the internal air path from microbial contamination buildup.
      METHODS: Five new intake filters were obtained directly from the manufacturer
      (Bair Hugger 505, model 200708D; Arizant Healthcare, Eden Prairie, MN), and 5
      model 200708C filters currently in hospital use were removed from FAW devices.
      The retention efficiency of these filters was assessed using a monodisperse
      sodium chloride aerosol. In the same hospitals, internal air path surface swabs
      and hose outlet particle counts were performed on 52 forced-air warming devices
      (all with the model 200708C filter) to assess internal microbial buildup and
      airborne contamination emissions. RESULTS: Intake filter retention efficiency at
      0.2 MUm was 93.8% for the 200708C filter and 61.3% at for the 200708D filter. The
      200708D filter obtained directly from the manufacturer has a thinner filtration
      media than the 200708C filter in current hospital use, suggesting that the
      observed differences in retention efficiency were due to design changes. Fifty
      eight percent of the FAW blowers evaluated were internally generating and
      emitting airborne contaminants, with microorganisms detected on the internal air
      path surfaces of 92.3% of these blowers. Isolates of Staphylococcus aureus,
      coagulase-negative Staphylococcus, and methicillin-resistant S aureus were
      detected in 13.5%, 3.9%, and 1.9% of FAW blowers, respectively. CONCLUSION: The
      design of popular FAW devices using the 200708C filter was found to be inadequate
      for preventing the internal buildup and emission of microbial contaminants into
      the operating room. Substandard intake filtration allowed airborne contaminants
      (both viable and nonviable) to penetrate the intake filter and reversibly attach
      to the internal surfaces within the FAW blowers. The reintroduction of these
      contaminants into the FAW blower air stream was detected and could contribute to
      the risk of cross-infection. Given the deficiencies identified with the 200708C
      intake filter, the introduction of a new filter (model 200708D) with
      substantially lower retention efficiency is of concern.

PMID- 21095042
TI  - Supplemental treatment of air in airborne infection isolation rooms using high
      throughput in-room air decontamination units.
AB  - BACKGROUND: Evidence has recently emerged indicating that in addition to large
      airborne droplets, fine aerosol particles can be an important mode of influenza
      transmission that may have been hitherto underestimated. Furthermore, recent
      performance studies evaluating airborne infection isolation (AII) rooms designed
      to house infectious patients have revealed major discrepancies between what is
      prescribed and what is actually measured. METHODS: We conducted an experimental
      study to investigate the use of high-throughput in-room air decontamination units
      for supplemental protection against airborne contamination in areas that host
      infectious patients. The study included both intrinsic performance tests of the
      air-decontamination unit against biological aerosols of particular epidemiologic
      interest and field tests in a hospital AII room under different ventilation
      scenarios. RESULTS: The unit tested efficiently eradicated airborne H5N2
      influenza and Mycobacterium bovis (a 4- to 5-log single-pass reduction) and, when
      implemented with a room extractor, reduced the peak contamination levels by a
      factor of 5, with decontamination rates at least 33% faster than those achieved
      with the extractor alone. CONCLUSION: High-throughput in-room air treatment units
      can provide supplemental control of airborne pathogen levels in patient isolation
      rooms.

PMID- 21095043
TI  - [Grounding public health policies in ethics and economic efficiency. SESPAS
      report 2010].
AB  - OBJECTIVES: In recent times, various voices in Spain have questioned public
      health policies as an assault to personal freedom. The present article aims to
      respond to these voices with ethical and economic arguments. METHODS: The scope
      and characteristics of this current of opinion are described. Then, starting with
      John Stuart Mill, the ethical principles of non-maleficence, beneficence,
      personal autonomy and justice, as well as related concepts taken from economic
      efficiency, such as externalities, monopoly, incomplete and asymmetric
      information, agency relationship, public goods and adverse selection, are
      discussed. A short mention is made of equity in economics, the welfare state and
      public health systems. The justification for paternalist actions by the state, as
      well as limits to these actions, are briefly discussed. CONCLUSION: Respect for
      individual freedom does not exclude the implementation of public health actions
      but rather demands the adoption of such policies. If these actions comply with
      certain conditions, they do not limit individual freedom but rather serve to
      protect it.

PMID- 21095044
TI  - [Climate change and health. SESPAS report 2010].
AB  - OBJECTIVES: To present the available evidence on the impacts of climate change on
      health, to analyze the situation in Spain in relation to the European context, to
      discuss barriers to and catalysts for climate change, and to recommend policy
      options to reduce the effects of climate change on health. METHODS: We reviewed
      the literature on the impact of climate change on health. The proposals for
      adaptation to climate change identified in the framework of the European project
      coordinated by the WHO/Europe on "Climate, Environment and Health action plans
      and information systems" were analyzed. RESULTS: The effects of climate change on
      health include: 1) an increase in the impacts of extreme weather events; 2) an
      increase of the frequency of respiratory diseases due to changes in air quality
      and pollen distribution; 3) an increase in the incidence of food-borne, zoonotic
      and waterborne diseases; and 4) a change in the distribution of infectious
      diseases and/or their vectors. In Spain, the morbidity and mortality due to heat
      waves are expected to increase. The main impact related to atmospheric
      contamination is a predicted increase in fine particles and ozone. There is also
      a risk of an increase in the geographical distribution of vector borne diseases
      that are already established in Spain or the establishment of new subtropical
      vectors. Spain is one of the first European countries to have developed a climate
      change adaptation plan. This plan provides a framework for coordination among
      public institutions on activities to evaluate the impacts of climate change, as
      well as vulnerability and adaptation to this phenomenon, and makes reference to
      the health sector. CONCLUSIONS: Policy options to reduce the impacts of climate
      change on health include: 1) integrating health in all policies, strategies and
      interventions to mitigate and adapt to climate change; 2) strengthening health
      systems and public health systems to improve their ability to prevent, prepare
      and respond to the impacts of climate change; 3) raising awareness among all
      sectors to promote the co-benefits to health of adaptation and mitigation
      strategies; and 4) promoting research, technological development, data sharing
      and information exchange across sectors.

PMID- 21095045
TI  - Strategies used by experienced versus novice practice teachers to enact their
      role with community nurse students.
AB  - This study offers an original analysis of how community nurse practice teachers
      learn to enact their role. A constructivist grounded theory approach was applied
      to a study of thirty community nurse practice teachers. Practice teachers were
      interviewed using a lightly structured interview approach following ethical
      approval. The study found that practice teachers considered relationships and
      nurturance to be of central importance. This led to emphasis being placed on
      providing experience for students and formative assessment. A number of key
      differences between the way novice and experienced practice teachers saw
      themselves functioning were discovered. These differences were theorised to
      explain the finding that novice practice teachers were much more likely to
      identify students as experiencing major difficulties than experienced practice
      teachers. It was discovered that practice teachers learn to enact their role
      within a socio-cultural context drawing upon a transformation approach to
      learning. This approach becomes firmly established over a period of approximately
      three years and is at odds with the current emphasis on competency based
      transmission models of learning.

PMID- 21095046
TI  - Teachers' experiences of English-language-taught degree programs within health
      care sector of Finnish polytechnics.
AB  - The purpose of this study was to research teachers' experiences of the English
      Language-Taught Degree Programs in the health care sector of Finnish
      polytechnics. More specifically, the focus was on teachers' experiences of
      teaching methods and clinical practice. The data were collected from eighteen
      teachers in six polytechnics through focus group interviews. Content analysis was
      used to analyse the data. The results suggested that despite the positive
      interaction between students and teachers, choosing appropriate teaching methods
      provided a challenge for teachers, due to cultural diversity of students as well
      as to the use of a foreign language in tuition. Due to students' language-related
      difficulties, clinical practice was found to be the biggest challenge in the
      educational process. Staffs' attitudes were perceived to be significant for
      students' clinical experience. Further research using stronger designs is needed.

PMID- 21095047
TI  - State of the art treatment of chronic lymphocytic leukaemia.
AB  - The management of chronic lymphocytic leukaemia is currently undergoing profound
      changes. Several drugs like bendamustine, alemtuzumab and rituximab have recently
      been approved for CLL treatment by regulatory agencies. New and very promising
      compounds like lenalidomide, ofatumumab, GA101, flavopiridol, or ABT-263 are
      currently investigated in clinical trials and are likely to further enlarge the
      therapeutic armamentarium in the next years. Latest results show that
      chemoimmunotherapies like FCR (fludarabine, cyclophosphamide and rituximab) may
      improve the life expectancy of CLL patients. This new paradigm will modify the
      way of CLL management in a radical manner. Finally, the development of new
      biological markers that describe distinct forms of CLL allows to enter the era of
      personalized therapy similar to other malignancies.

PMID- 21095049
TI  - Mineralisation of target hydrocarbons in three contaminated soils from former
      refinery facilities.
AB  - This study investigated the microbial degradation of (14)C-labelled hexadecane,
      octacosane, phenanthrene and pyrene and considered how degradation might be
      optimised in three genuinely hydrocarbon-contaminated soils from former petroleum
      refinery sites. Hydrocarbon mineralisation by the indigenous microbial community
      was monitored over 23 d. Hydrocarbon mineralisation enhancement by nutrient
      amendment (biostimulation), hydrocarbon degrader addition (bioaugmentation) and
      combined nutrient and degrader amendment, was also explored. The ability of
      indigenous soil microflora to mineralise (14)C-target hydrocarbons was
      appreciable; >= 16% mineralised in all soils. Generally, addition of nutrients or
      degraders increased the rates and extents of mineralisation of (14)C
      hydrocarbons. However, the addition of nutrients and degraders in combination had
      a negative effect upon (14)C-octacosane mineralisation and resulted in lower
      extents of mineralisation in the three soils. In general, the rates and extents
      of mineralisation will be dependent upon treatment type, nature of the
      contamination and adaptation of the ingenious microbial community.

PMID- 21095050
TI  - Oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) in urban soils of
      Bratislava, Slovakia: patterns, relation to PAHs and vertical distribution.
AB  - We determined concentrations, sources, and vertical distribution of OPAHs and
      PAHs in soils of Bratislava. The ?14 OPAHs concentrations in surface soil
      horizons ranged 88-2692 ng g(-1) and those of ?34 PAHs 842-244,870 ng g(-1). The
      concentrations of the ?9 carbonyl-OPAHs (r=0.92, p=0.0001) and the ?5 hydroxyl
      OPAHs (r=0.73, p=0.01) correlated significantly with ?34 PAHs concentrations
      indicating the close association of OPAHs with parent-PAHs. OPAHs were
      quantitatively dominated by 9-fluorenone, 9,10-anthraquinone, 1-indanone and
      benzo[a]anthracene-7,12-dione. At several sites, individual carbonyl-OPAHs had
      higher concentrations than parent PAHs. The concentration ratios of several OPAHs
      to their parent-PAHs and contribution of the more soluble OPAHs (1-indanone and 9
      fluorenone) to ?14 OPAHs concentrations increased with soil depth suggesting that
      OPAHs were faster vertically transported in the study soils by leaching than PAHs
      which was supported by the correlation of subsoil:surface soil ratios of OPAH
      concentrations at several sites with K(OW).

PMID- 21095051
TI  - A review of technology-assisted self-help and minimal contact therapies for drug
      and alcohol abuse and smoking addiction: is human contact necessary for
      therapeutic efficacy?
AB  - Technology-based self-help and minimal contact therapies have been proposed as
      effective and low-cost interventions for addictive disorders, such as nicotine,
      alcohol, and drug abuse and addiction. The present article reviews the literature
      published before 2010 on computerized treatments for drug and alcohol abuse and
      dependence and smoking addiction. Treatment studies are examined by disorder as
      well as amount of therapist contact, ranging from self-administered therapy and
      predominantly self-help interventions to minimal contact therapy where the
      therapist is actively involved in treatment but to a lesser degree than
      traditional therapy and predominantly therapist-administered treatments involving
      regular contact with a therapist for a typical number of sessions. In the
      treatment of substance use and abuse it is concluded that self-administered and
      predominantly self-help computer-based cognitive and behavioral interventions are
      efficacious, but some therapist contact is important for greater and more
      sustained reductions in addictive behavior.

PMID- 21095048
TI  - JAK2 inhibitors: what's the true therapeutic potential?
AB  - Physicians treating patients with the classic Philadelphia-negative
      myeloproliferative neoplasms (Ph-negative MPNs) (polycythemia vera [PV],
      essential thrombocythemia [ET] and primary myelofibrosis [PMF]) traditionally had
      few therapeutic drugs available. Spurred by the discovery of activating mutation
      of the JAK2 tyrosine kinase (JAK2 V617F mutation) in patients with Ph-negative
      MPNs several years ago, several JAK2 inhibitors were synthesized and are
      currently undergoing clinical trials in patients with PMF, PV and ET. Initial
      results from these studies have shown that these drugs can markedly reduce spleen
      size and alleviate constitutional symptoms, increase weight and improve exercise
      capacity in MF patients, thus improve quality of their life, which is significant
      clinical benefit. In ET and PV JAK2 inhibitor therapy may efficiently control
      blood cell count, as well as improve splenomegaly and control disease related
      symptoms. JAK2 inhibitors are a novel class of agents with promising results for
      treating patients with MF, PV and ET. In this article we will review the current
      evidence regarding the role of JAK2 mutations in the pathogenesis of Ph-negative
      MPNs and summarize results from the most recent clinical trials with JAK2
      inhibitors in these disorders. JAK2 inhibitors are a novel class of agents with
      promising results for treating patients with MF, PV and ET.

PMID- 21095052
TI  - The influence of culture on home-based family caregiving at end-of-life: a case
      study of Dutch reformed family care givers in Ontario, Canada.
AB  - Families are facing increased pressure to provide care to their terminally-ill or
      dying kin in the home. It is known that balancing care with other personal and
      social roles can adversely affect family caregivers' (FCGs) health, yet access to
      supportive services which can mitigate burden is often inadequate. Cultural
      factors are known to shape the experience of caregiving; however, most research
      to date tends to neglect the experiences of FCGs from different cultural groups.
      This understanding is necessary to ensure that supportive services are both
      meaningful and culturally-appropriate. Using qualitative methods, we undertook
      longitudinal research with a sample of Dutch Reformed FCGs (n = 5) to understand
      their experiences of caregiving and bereavement. The results of the study are
      suggestive of a cultural specificity with respect to caregiving that impacts both
      responsibilities and reactions to care. Three themes were salient to this group
      as a cultural entity: cultural attitudes towards care, religious beliefs and
      coping, and culturally-informed care-seeking behaviours. These three themes were
      seen to be a function of their religious and ethnic identities and were
      reinforced by ties to the communities in which they resided. Cultural identity
      provided a framework through which to understand and make sense of the
      experience, while group membership provided access to networks of informal
      support. This research contributes to the geographical literature on
      care/caregiving by providing insight into the social, cultural and religious
      context of informal family caregiving with a population who live in close
      geographic proximity. On a practical level, this case study indicates the
      importance of considering how these factors may operate in other settings in
      order to implement timely and appropriate interventions to better support FCGs
      who are caring for their terminally-ill loved-ones at home.

PMID- 21095053
TI  - Individual differences in cognitive-flexibility: the influence of spontaneous
      eyeblink rate, trait psychoticism and working memory on attentional set-shifting.
AB  - Individual differences in psychophysiological function have been shown to
      influence the balance between flexibility and distractibility during attentional
      set-shifting [e.g., Dreisbach et al. (2005). Dopamine and cognitive control: The
      influence of spontaneous eyeblink rate and dopamine gene polymorphisms on
      perseveration and distractibility. Behavioral Neuroscience, 119(2), 483-490].
      Here we replicate both the facilitatory and detrimental influence of spontaneous
      eyeblink rate upon switch costs across the two distinct conditions of a set
      shifting task. We extend this by presenting additional, putatively dopamine
      related, individual differences that also influence attentional control. Whereas
      trait psychoticism showed a pattern of effects opposite to that of eyeblink rate,
      greater working memory served to decrease switch costs across both conditions.
      These results highlight the need for further exploration of the role of
      dopaminergic neurotransmission and component processes involved in such
      attentional paradigms, and illustrates the importance of considering individual
      differences in cognitive control.

PMID- 21095054
TI  - Retrospective analysis of emergency room thoracotomy in pediatric severe trauma
      patients.
AB  - BACKGROUND: Although the integral role of ED thoracotomy for open cardiac massage
      has been extensively reviewed in adult literature, this "heroic maneuver" remains
      very controversial and greatly debated in children. METHODS AND RESULTS: A
      retrospective cohort review of emergency thoracotomies in children, performed at
      a European Level I trauma center between 1992 and 2008 was undertaken. Clinical
      manifestation, injury mechanism and surgical treatment were described, with
      special regard to prognostic factors and outcome. A total of eleven thoracotomies
      were performed, ten for blunt injuries (91%), and one for perforating injury
      (9%), with a mean age of 7.8 years, range 2.6-15.4 years, comprising eight boys
      and three girls. The mean Injury Severity Score of the children with blunt force
      trauma was 46, ranging from 25 to 66 compared with 20 of the penetrating trauma
      victim. Ten of eleven patients (91%) who underwent ED thoracotomy died. Nine of
      them were in cardiac arrest on arrival. One patient who had a penetrating knife
      injury and had stable vital sign on arrival survived. CONCLUSIONS: Similar to
      previous studies, out data confirmed ED thoracotomy for children in cardiac
      arrest from blunt trauma had universally fatal outcome. The mechanism of injury
      and signs of life at arrival were predictive key factors that influence the
      outcome of ED thoracotomy.

PMID- 21095055
TI  - Cancer control and functional outcomes after radical prostatectomy as markers of
      surgical quality: analysis of heterogeneity between surgeons at a single cancer
      center.
AB  - BACKGROUND: Previous studies have shown that complications and biochemical
      recurrence rates after radical prostatectomy (RP) vary between different surgeons
      to a greater extent than might be expected by chance. Data on urinary and
      erectile outcomes, however, are lacking. OBJECTIVE: In this study, we examined
      whether between-surgeon variation, known as heterogeneity, exists for urinary and
      erectile outcomes after RP. DESIGN, SETTING, AND PARTICIPANTS: Our study
      consisted of 1910 RP patients who were treated by 1 of 11 surgeons between
      January 1999 and July 2007. INTERVENTION: All patients underwent RP at Memorial
      Sloan-Kettering Cancer Center. MEASUREMENTS: Patients were evaluated for
      functional outcome 1 yr after surgery. Multivariable random effects models were
      used to evaluate the heterogeneity in erectile or urinary outcome between
      surgeons, after adjustment for case mix (age, prostate-specific antigen,
      pathologic stage and grade, comorbidities) and year of surgery. RESULTS AND
      LIMITATIONS: We found significant heterogeneity in functional outcomes after RP
      (p<0.001 for both urinary and erectile function). Four surgeons had adjusted
      rates of full continence <75%, whereas three had rates >85%. For erectile
      function, two surgeons in our series had adjusted rates <20%; another two had
      rates >45%. We found some evidence suggesting that surgeons' erectile and urinary
      outcomes were correlated. Contrary to the hypothesis that surgeons "trade off"
      functional outcomes and cancer control, better rates of functional preservation
      were associated with lower biochemical recurrence rates. CONCLUSIONS: A patient's
      likelihood of recovering erectile and urinary function may differ depending on
      which of two surgeons performs his RP. Functional preservation does not appear to
      come at the expense of cancer control; rather, both are related to surgical
      quality.

PMID- 21095056
TI  - Is the surgical repair of unruptured atherosclerotic aneurysms at a higher risk
      of intraoperative ischemia?
AB  - BACKGROUND: The incidence of ischemia might be increased in the surgical repair
      of atherosclerotic unruptured aneurysms compared to non-atherosclerotic
      aneurysms. The atherosclerotic wall might increase the occurrence of
      thrombembolic events or its rigidity might endanger the occlusion of perforators
      within the aneurysm vicinity. METHODS: 87 patients (53 patients without and 34
      patients with atherosclerotic unruptured aneurysms, 50.5 +/- 9.7 years) were
      analyzed for severity of atherosclerosis within the aneurysm and the aneurysm
      bearing vessel, surgical maneuvers, intraoperative alterations in evoked
      potentials and clinical and neuroradiological results. RESULTS: Temporary vessel
      occlusion (25% vs. 50%, p = 0.021), repositioning of a permanent clip (21% vs.
      56%, p = 0.001) and aneurysm remnants (2% vs. 18%, p = 0.012) occurred more often
      in patients with atherosclerotic aneurysms. At 6 months, 3/34 patients with
      atherosclerosis (8.8%) had an unfavorable outcome, all patients without
      atherosclerosis had a favorable outcome (p = 0.056). CONCLUSION: The surgical
      repair of unruptured aneurysms is safe but patients with atherosclerotic altered
      vessels and aneurysms accounted to a minor increase in unfavorable outcome and an
      increased risk of morbidity at 6 months postoperatively. This factor should be
      taken into consideration when performing surgery of atherosclerotic, unruptured
      aneurysms.

PMID- 21095057
TI  - In vitro binding capacities of three dietary fibers and their mixture for four
      toxic elements, cholesterol, and bile acid.
AB  - Water-soluble dietary fibers from apple peels and water-insoluble dietary fibers
      from wheat bran and soybean-seed hull were used to evaluate their binding
      capacities for four toxic elements (Pb, Hg, Cd, and As), lard, cholesterol, and
      bile acids. The water-soluble dietary fibers showed a higher binding capacity for
      three toxic cations, cholesterol, and sodium cholate; and a lower binding
      capacity for lard, compared to the water-insoluble ones. A mixture of the dietary
      fibers from all samples - apple peels, wheat bran, and soybean-seed hull - in the
      ratio 2:4:4 (w/w) significantly increased the binding capacity of water-insoluble
      dietary fibers for the three toxic cations, cholesterol, and sodium cholate;
      moreover, the mixture could lower the concentrations of Pb(2+) and Cd(+) in the
      tested solutions to levels lower than those occurring in rice and vegetables
      grown in polluted soils. However, all the tested fibers showed a low binding
      capacity for the toxic anion, AsO(3)(3-).

PMID- 21095058
TI  - Ni(2+) and H(2)PO(4)(-) uptake properties of compounds in the CaTiO(3)-CaFeO(2.5)
      system.
AB  - A batch method was used to investigate the uptake of heavy metal cations and
      anions by the compounds in the CaTiO(3)-CaFeO(2.5) system, in which a series of
      oxygen vacancies was systematically introduced into a perovskite structure as the
      x-value of Ca(Fe(x)Ti(1-x))O(3-x/2) was increased. Samples of CaTiO(3),
      CaFe(0.1)Ti(0.9)O(2.95), CaFe(0.5)Ti(0.5)O(2.75), CaFe(0.67)Ti(0.33)O(2.67) and
      CaFeO(2.5) were prepared by solid mixing (SM), co-precipitation (CP) and gel
      evaporation (GE) methods. The resulting samples were calcined at temperatures
      between 400 and 1000  degrees C. The target crystalline phases differed according
      to the preparation method, but in most cases were formed at 700-800  degrees C.
      The Ni(2+) sorption isotherms of all the samples were fitted better by the
      Langmuir model than by the Freundlich model, while in the case of H(2)PO(4)(-)
      sorption isotherms, these were better fitted by the latter model. The uptake
      ability increased with increasing x value of the samples. The maximum values for
      the saturated sorption of Ni(2+) (Q(0)(Ni(2+)) = 2.83 mmol/g) and H(2)PO(4)(-)
      (K(F)(H(2)PO(4)(-)) = 2.95 mmol/g) were achieved for x = 1 (i.e. CaFeO(2.5))
      sample.

PMID- 21095060
TI  - Determination of a risk management primer at petroleum-contaminated sites:
      developing new human health risk assessment strategy.
AB  - Total petroleum hydrocarbon (TPH) is an important environmental contaminant that
      is toxic to human and environmental receptors. However, human health risk
      assessment for petroleum, oil, and lubricant (POL)-contaminated sites is
      especially challenging because TPH is not a single compound, but rather a mixture
      of numerous substances. To address this concern, this study recommends a new
      human health risk assessment strategy for POL-contaminated sites. The strategy is
      based on a newly modified TPH fractionation method and includes an improved
      analytical protocol. The proposed TPH fractionation method is composed of ten
      fractions (e.g., aliphatic and aromatic EC8-10, EC10-12, EC12-16, EC16-22 and
      EC22-40). Physicochemical properties and toxicity values of each fraction were
      newly defined in this study. The stepwise ultrasonication-based analytical
      process was established to measure TPH fractions. Analytical results were
      compared with those from the TPH Criteria Working Group (TPHCWG) Direct Method.
      Better analytical efficiencies in TPH, aliphatic, and aromatic fractions were
      achieved when contaminated soil samples were analyzed with the new analytical
      protocol. Finally, a human health risk assessment was performed based on the
      developed tiered risk assessment framework. Results showed that a detailed
      quantitative risk assessment should be conducted to determine scientifically and
      economically appropriate cleanup target levels, although the phase II process is
      useful for determining the potency of human health risks posed by POL
      contamination.

PMID- 21095059
TI  - Photodegradation of crystal violet in TiO(2) suspensions using UV-vis irradiation
      from two microwave-powered electrodeless discharge lamps (EDL(-2)): products,
      mechanism and feasibility.
AB  - Aqueous crystal violet (CV) solutions containing P25-TiO(2) photocatalyst were
      irradiated with ultraviolet-visible (UV-vis) light from two microwave-powered
      electrodeless discharge lamps (EDL(-2)). The results demonstrated that
      approximately 94.4% of CV was effectively removed after 3 min of irradiation,
      with a pseudo-first order kinetic constant of 0.838 min(-1). According to 32
      kinds of products, a five-step degradation pathway of CV was proposed. Further
      investigations showed that (1) three kinds of N-demethylated products and 4
      dimethylaminobenzophenone (DLBP) were the main intermediates; (2) malachite green
      (MG) and leuco-crystal violet could not be generated by N-demethylation and
      phototransformation reactions, respectively; (3) bis(4
      (dimethylamino)phenyl)methanone preferentially generated via decomposition of the
      conjugated structure of CV could be further N-demethylated into DLBP. Moreover,
      the unique degradation pathways of CV and MG were ascribed to the different
      substituents on the conjugated structures. Additionally, the cost and kinetic
      constant of different processes was also evaluated, and the results indicated the
      feasibility of this method for treatment of CV in field situations.

PMID- 21095061
TI  - Larval development of Toxocara canis in dogs.
AB  - The parasitic roundworm Toxocara canis is present in dog populations all over the
      world. Due to its zoonotic potential, this roundworm is of special interest not
      only for veterinarians, but also for medical practitioners. In the present
      review, current knowledge of infection routes and the subsequent development of
      larvae within the canine host is summarised. Furthermore, information about the
      clinical, pathological, enzymatic, haematological and histopathological changes
      was collected, giving a broad overview of current knowledge of the infection.
      Although the data collected over the years give an idea of what happens during
      the larval development of T. canis, many questions remain open. Nevertheless, it
      is important that we continue our efforts to further understand the biology of
      this versatile and compelling parasite and try to improve and optimise strategies
      to prevent the infection in dogs and thereby to protect humans from this
      infection.

PMID- 21095062
TI  - Optimizing initial vancomycin dosing in burn patients.
AB  - RATIONALE: Burned patients have altered vancomycin pharmacokinetics necessitating
      adjusted dosing. Published initial dosing recommendations to target troughs of 15
      20mg/L for this population are lacking. OBJECTIVE: This study was conducted to
      develop initial vancomycin dosing recommendations based on the pharmacokinetics
      of vancomycin in acute burn patients. METHODS: A retrospective chart review of 49
      vancomycin treated burn patients was conducted. Mean pharmacokinetic parameters
      were determined and Monte Carlo Simulation was used to develop initial vancomycin
      dosing recommendations that target trough concentrations between 15 and 20mg/L.
      RESULTS: Vancomycin pharmacokinetic parameters were significantly (p < 0.05)
      different for vancomycin levels obtained 48 h to 14 days after burn versus >14
      days after burn. Monte Carlo simulation indicated that the most commonly used
      empiric dosing regimen (1g iv q12 h) attained targets with a probability of <10%
      in all burned patients. The probability of attaining targets was optimized to 20
      25% by using 1.5 g iv q8 h, 1.75 g iv q8 h, 1g iv q6 h, 1.25g iv q6 h or 750 mg
      iv q4 h in patients 48 h to 14 days after burn and 1-1.25 g iv q8 h or 500 mg iv
      q4 h in patients >14 days after burn. CONCLUSIONS: This study provides initial
      vancomycin dosing recommendations for burned patients 48 h to 14 days after burn
      and patients >14 days after burn. However, because of the heterogeneity in
      pharmacokinetics and the observation that vancomycin pharmacokinetics change with
      time after burn, monitoring of vancomycin serum concentrations is required to
      ensure targets are met and maintained.

PMID- 21095064
TI  - Human mineralocorticoid receptor (MR) gene haplotypes modulate MR expression and
      transactivation: implication for the stress response.
AB  - Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis,
      resulting in secretion of corticosteroids which facilitate behavioural
      adaptation. These effects exerted by corticosteroids are mediated by two brain
      corticosteroid receptor types, the mineralocorticoid receptor (MR), with a high
      affinity already occupied under basal conditions and the glucocorticoid receptor
      (GR), with a low affinity only activated during stress. Here, we studied MR gene
      haplotypes constituted by the two single nucleotide polymorphisms MR-2G/C
      (rs2070951) and MRI180V (rs5522). The haplotypes showed differences in cortisol
      induced gene transcription and protein expression while the structural variant
      MRI180V did not affect ligand binding. Moreover, in a well characterized cohort
      of 166 school teachers these haplotypes have been associated with perceived
      chronic stress (Trier Inventory for the Assessment of Chronic Stress, TICS) and,
      in a subgroup of 47 subjects, with ACTH, cortisol and heart rate responses to
      acute psychosocial stress (Trier Social Stress Test, TSST). MR haplotypes were
      significantly associated with the TICS scales "excessive demands at work" and
      "social overload". Subjects homozygous for haplotype MR-2C/MRI180, which in vitro
      showed highest expression and transactivational activity, displayed the highest
      salivary cortisol (p<0.001), plasma cortisol (p=0.010), plasma ACTH (p=0.003) and
      heart rate (p=0.018) responses. It is concluded that the investigated MR
      haplotypes modulate cortisol-induced gene transcription in vitro. Moreover, these
      haplotypes may contribute to individual differences in perceived chronic stress
      as well as neuroendocrine and cardiovascular stress responses.

PMID- 21095063
TI  - Effects of social isolation on mRNA expression for corticotrophin-releasing
      hormone receptors in prairie voles.
AB  - Previous studies have demonstrated that various type of stressors modulate
      messenger ribonucleic acid (mRNA) for type 1 corticotropin-releasing hormone
      (CRH) receptor (CRH-R1 mRNA) and type 2 CRH receptor (CRH-R2 mRNA). The purpose
      of this study was to explore the effect of social isolation stress of varying
      durations on the CRH, CRH-R1 and CRH-R2 mRNAs expression in the hypothalamus,
      hippocampus and pituitary of socially monogamous female and male prairie voles
      (Microtus ochrogaster). Isolation for 1h (single isolation) or 1h of isolation
      every day for 4 weeks (repeated isolation) was followed by a significant increase
      in plasma corticosterone levels. Single or repeated isolation increased
      hypothalamic CRH mRNA expression, but no changes in CRH-R1 mRNA in the
      hypothalamus were observed. Continuous isolation for 4 weeks (chronic isolation)
      showed no effect on hypothalamic CRH or CRH-R1 mRNAs in female or male animals.
      However, hypothalamic CRH-R2 mRNA was significantly reduced in voles exposed to
      chronic isolation. Single or repeated isolation, but not chronic isolation,
      significantly increased CRH-R1 mRNA and decreased CRH-R2 mRNA in the pituitary.
      Despite elevated CRH mRNA expression, CRH-R1 and CRH-R2 mRNAs were not modulated
      in the hippocampus following single or repeated isolation. Although, chronic
      isolation did not affect hippocampal CRH or CRH-R1 mRNAs, it did increase CRH-R2
      mRNA expression in females and males. The results of the present study in prairie
      voles suggest that social isolation has receptor subtype and species-specific
      consequences for the modulation of gene expression for CRH and its receptors in
      brain and pituitary. Previous studies have revealed a female-biased increase in
      oxytocin in response to chronic isolation; however, we did not find a sex
      difference in CRH or its receptors following single, repeated or chronic social
      isolation, suggesting that sexually dimorphic processes beyond the CRH system,
      possibly involving vasopressin, might explain this difference.

PMID- 21095066
TI  - The roots of sexual arousal and sexual orientation.
AB  - Unlike members of other species that are genetically wired to be attracted to
      their sexual partners, humans learn the cues that guide them in choosing their
      sexual partners and that trigger sexual arousal. Genetically wired mechanisms
      must be directing the acquisition of those cues and organizing them in
      information structures that underlie human sexual behavior. Individual sexuality
      is a combination of the genetic mechanisms and information learned through
      personal experiences. This article focuses on the roots of human sexuality - on
      genetically embedded mechanisms, common to all humans, around which the wide
      variety of sexual behaviors is built. It proposes a model that defines the basic
      mechanisms and their role in developing individual sexuality. It is suggested
      that three brain areas host the roots of human sexuality: the auditory area,
      which provides stimuli that serve as cues for the identification of a mate; an
      emotional area, which provides cues for emotional arousal; and a corporal area,
      which controls the physiological expressions of arousal. The amygdala is a main
      candidate for the emotional area, and the hypothalamus for the corporal area, but
      other areas may also provide those inputs. Experimental observations that support
      this model are discussed, and an outline of additional experiments for validating
      the model is proposed. If validated, the model would provide knowledge that fills
      a gap in the understanding of human sexuality - knowledge that would benefit
      individuals, the medical profession, and society as a whole.

PMID- 21095065
TI  - Synchronized dance therapy to stimulate mirror neurons in autism.

PMID- 21095067
TI  - Is CD146 pivotal in neoplasm invasion and blastocyst embedding?
AB  - Blastocyst embedding is very similar to neoplasm invasion. Blastocyst embedding
      is seeding the young plant of life, while neoplasm invasion is knocking at the
      door of death. Overexpression of melanoma cell adhesion molecule (CD146 or MCAM),
      a novel member of the immunoglobulingene superfamily, promotes invasion,
      metastasis, growth and survival of malignant cells, and implantation of
      blastocyst embedding in placenta. We hypothesize that CD146 may be a key gene
      both in neoplasm invasion and blastocyst embedding because of its ability in
      regulating cell invasion. The regulation of CD146 expression may be a control
      switch in the progress of the neoplasm invasion and blastocyst embedding. If the
      hypothesis is correct, the inhibition of CD146 can be used to prevent and/or
      treat tumor invasion. Current treatment modalities of tumor invasion include
      different therapies: surgical resection, radiotherapy, chemotherapy, etc. These
      treatments are all non-specific to tumor cells. If further studies proof our
      hypothesis, CD146 may be a candidate target gene in gene therapy of tumor
      invasion and in regulation of blastocyst embedding.

PMID- 21095068
TI  - Synthetic aromatic compounds interfering with melanogenesis are responsible of
      the rising trend of malignant melanoma incidence.
AB  - The hypotheses is forwarded that the introduction in the environment of high
      concentrations of phenols and other aromatic compounds (AC) is one, perhaps the
      main cause of the continuously rising trend of malignant melanoma (MM) incidence.
      Two, non-mutually exclusive, possibilities could explain how AC may induce MM:
      (1) AC may act as inhibitors or alternative substrates of tyrosinase, the enzyme
      synthesizing melanin, thus impairing the melanocyte photoprotection. (2) AC may
      impair, directly or indirectly, the activity or synthesis of the
      melanocorticotropin receptor (MC1R), which photoprotects melanocytes from the UV
      rays (UVR) by stimulating the DNA repair system. Particularly suspected are
      sunscreens, as they contain high concentrations of a large variety of AC, three
      of which are known to be tyrosinase inhibitors. AC that may interfere with
      tyrosinase are also present in a large variety of medicines used orally or as
      creams, and in many industrial products with which man is frequently in contact.

PMID- 21095069
TI  - HER2-positive status is an independent predictor for coexisting invasion of
      ductal carcinoma in situ of the breast presenting extensive DCIS component.
AB  - DCIS of the breast with coexisting invasion is commonly seen, and no consensus on
      any biomarker capable of discriminating this subgroup has been reached yet. We
      retrospectively examined the receptor status and the histological grade in
      Chinese DCIS patients to identify any independent predictor in order to
      discriminate a subgroup with coexisting invasion from pure DCIS patients. A
      consecutive Chinese DCIS patient cohort registered at a single institution was
      included for ER, PR, and HER2 status, as well as for evaluation of the
      histological grade. Patients with invasion foci >1cm in diameter were excluded.
      The HER2 gene amplification status was further examined by FISH when the IHC
      result was HER2 (2+). Molecular subtypes were also profiled. Age, histological
      grade, ER, PR, and HER2 status were included in association analyses. In total,
      183 patients were included. A hundred and forty patients had pure DCIS, and 43
      patients had DCIS with invasion. The luminal A subtype accounted for 49.7% of all
      cases, the HER2-positive subtype for 27.9%, and only 10.4% and 12.0% represented
      the luminal B and basal-like subtypes, respectively. Univariate analyses showed
      that histological Grade 2, Grade 3, and HER2-positive status were associated with
      DCIS with invasion, odds ratios 5.1 (P = 0.017), 5.2 (P = 0.01) and 3.34 (P =
      0.001), respectively. However, only the HER2-positive status was of statistical
      significance in the multivariate logistic regression analyses after adjustment
      for other markers, odds ratio 3.8 (95%CI 1.4-10, P = 0.008). The 43 cases with
      invasion were further stratified into extensive or small DCIS components
      according to the percentage of DCIS to total tumor area using 25% as the cutoff
      point. Multinomial logistic regression with pure DCIS cases as reference showed
      that the HER2-positive status was associated only with the group showing an
      extensive DCIS component, odds ratio 6.2 (95%CI 1.8-21, P = 0.003), but not with
      the group having a small DCIS component. Our study demonstrates that HER2
      positive status is an independent predictor for DCIS, with invasion presenting an
      extensive DCIS component, and favors the hypothesis that HER2 overexpression or
      gene amplification is involved in the transition from DCIS to invasive disease.

PMID- 21095070
TI  - Intravenous lipoleiomyomatosis of uterus with cardiac extension: a case report.
AB  - A case of intravenous leiomyomatosis (IVL) with histological features of a
      lipoleiomyoma (intravenous lipoleiomyoma) in a 48-year-old woman is reported. The
      patient, with the tumor located in the uterus and extended up on the right side
      of the heart through the inferior vena cava, was diagnosed as having a cardiac
      mass. She displayed symptoms of dyspnea, chest pain due to the cardiac mass, as
      well as pelvic pain and dysmenorrhea. She underwent cardiac surgery because of a
      right atrial mass, and the histopathological diagnosis was leiomyoma without the
      knowledge of a uterine mass. Afterwards, a right adnexial mass was detected in
      the pelvis, and a total hysterectomy-bilateral salpingo-oophorectomy was
      performed for the adnexial mass, which was also diagnosed as leiomyoma. In this
      case report, we describe an intravenous lipoleiomyomatosis of the uterus which,
      at the initial clinical presentation, showed cardiovascular symptoms. We
      emphasize the histopathological features and the differential diagnosis of this
      rare tumor in the light of the literature.

PMID- 21095071
TI  - Dose-painted intensity-modulated radiation therapy for anal cancer: a multi
      institutional report of acute toxicity and response to therapy.
AB  - PURPOSE: Chemoradiation for anal cancer yields effective tumor control, but is
      associated with significant acute toxicity. We report our multi-institutional
      experience using dose-painted IMRT (DP-IMRT). PATIENTS AND METHODS: Between
      August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent
      chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two
      academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5
      Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8
      Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54
      Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68
      Gy/fx to nodal PTVs <= 3 cm in size. Acute and late toxicity was reported by the
      treating physician. Actuarial analysis was performed using the Kaplan-Meier
      method. RESULTS: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42%
      III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on
      chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5
      months). Sixty percent completed chemoradiation without treatment interruption;
      median duration of treatment interruption was 2 days (range, 2-24 days). Acute
      Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal
      7%, and genitourinary 7%. Two-year local control, overall survival, colostomy
      free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%,
      respectively. CONCLUSIONS: Dose-painted IMRT appears effective and well-tolerated
      as part of a chemoradiation therapy regimen for the treatment of anal canal
      cancer.

PMID- 21095072
TI  - Impact of [11C]methionine positron emission tomography for target definition of
      glioblastoma multiforme in radiation therapy planning.
AB  - PURPOSE: The purpose of this work was to define the optimal margins for
      gadolinium-enhanced T(1)-weighted magnetic resonance imaging (Gd-MRI) and T(2)
      weighted MRI (T(2)-MRI) for delineating target volumes in planning radiation
      therapy for postoperative patients with newly diagnosed glioblastoma multiforme
      (GBM) by comparison to carbon-11-labeled methionine positron emission tomography
      ([(11)C]MET-PET) findings. METHODS AND MATERIALS: Computed tomography (CT), MRI,
      and [(11)C]MET-PET were separately performed for radiation therapy planning for
      32 patients newly diagnosed with GBM within 2 weeks after undergoing surgery. The
      extent of Gd-MRI (Gd-enhanced clinical target volume [CTV-Gd]) uptake and that of
      T(2)-MRI of the CTV (CTV-T(2)) were compared with the extent of [(11)C]MET-PET
      (CTV--[(11)C]MET-PET) uptake by using CT--MRI or CT--[(11)C]MET-PET fusion
      imaging. We defined CTV-Gd (x mm) and CTV-T(2) (x mm) as the x-mm margins (where
      x = 0, 2, 5, 10, and 20 mm) outside the CTV-Gd and the CTV-T(2), respectively. We
      evaluated the relationship between CTV-Gd (x mm) and CTV-- [(11)C]MET-PET and the
      relationship between CTV-T(2) (x mm) and CTV-- [(11)C]MET-PET. RESULTS: The
      sensitivity of CTV-Gd (20 mm) (86.4%) was significantly higher than that of the
      other CTV-Gd. The sensitivity of CTV-T(2) (20 mm) (96.4%) was significantly
      higher than that of the other CTV-T(2) (x = 0, 2, 5, 10 mm). The highest
      sensitivity and lowest specificity was found with CTV-T(2) (x = 20 mm).
      CONCLUSIONS: It is necessary to use a margin of at least 2 cm for CTV-T(2) for
      the initial target planning of radiation therapy. However, there is a limit to
      this setting in defining the optimal margin for Gd-MRI and T(2)-MRI for the
      precise delineation of target volumes in radiation therapy planning for
      postoperative patients with GBM.

PMID- 21095073
TI  - Progression of non-small-cell lung cancer during the interval before stereotactic
      body radiotherapy.
AB  - PURPOSE: To investigate the relationship between waiting time (WT) and disease
      progression in patients undergoing stereotactic body radiotherapy (SBRT) for lung
      adenocarcinoma (AD) or squamous cell carcinoma (SQ). METHODS AND MATERIALS: 201
      patients with Stage I AD or SQ undergoing SBRT between January 2004 and June 2010
      were analyzed. The WT was defined as the interval between diagnostic computed
      tomography before referral and computed tomography for treatment planning or
      positioning before SBRT. Tumor size was measured on the slice of the longest
      tumor diameter, and tumor volume was calculated from the longest diameter and the
      diameter perpendicular to it. Changes in tumor volume and TNM stage progression
      were evaluated, and volume doubling time (VDT) was estimated. RESULTS: The median
      WT was 42 days (range, 5-323 days). There was a correlation between WT and rate
      of increase in volume in both AD and SQ. The median VDTs of AD and SQ were 170
      and 93 days, respectively. Thirty-six tumors (23%) did not show volume increase
      during WTs >25 days. In 41 patients waiting for <=4 weeks, no patient showed T
      stage progression, whereas in 25 of 120 (21%) patients waiting for >4 weeks, T
      stage progressed from T1 to T2 (p = 0.001). In 10 of 110 (9.1%) T1 ADs and 15 of
      51 (29%) T1 SQs, T stage progressed (p = 0.002). N stage and M stage progressions
      were not observed. CONCLUSION: Generally, a WT of <=4 weeks seems to be
      acceptable. The WT seems to be more important in SQ than in AD.

PMID- 21095074
TI  - Long-term outcome and morbidity after treatment with accelerated radiotherapy and
      weekly cisplatin for locally advanced head-and-neck cancer: results of a
      multidisciplinary late morbidity clinic.
AB  - PURPOSE: To evaluate the long-term outcome and morbidity after intensified
      treatment for locally advanced head-and-neck cancer. METHODS AND MATERIALS:
      Between May 2003 and December 2007, 77 patients with Stage III to IV head-and
      neck cancer were treated with curative intent. Treatment consisted of accelerated
      radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors
      were invited to a multidisciplinary outpatient clinic for a comprehensive
      assessment of late morbidity with special emphasis on dysphagia, including
      radiological evaluation of swallowing function in all patients. RESULTS:
      Compliance with the treatment protocol was high, with 87% of the patients
      receiving at least five cycles of cisplatin and all but 1 patient completing the
      radiotherapy as planned. The 5-year actuarial disease-free survival and overall
      survival rates were 40% and 47%, respectively. Locoregional recurrence-free
      survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation
      Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of
      Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively.
      Radiologic evaluation after a median follow-up of 44 months demonstrated impaired
      swallowing in 57% of the patients, including 23% with silent aspiration.
      Subjective assessment using a systematic scoring system indicated normalcy of
      diet in only 15.6% of the patients. CONCLUSION: This regimen of accelerated
      radiotherapy with weekly cisplatin produced favorable tumor control rates and
      survival rates while compliance was high. However, comprehensive assessment by a
      multidisciplinary team of medical and paramedical specialists revealed
      significant long-term morbidity in the majority of the patients, with dysphagia
      being a major concern.

PMID- 21095075
TI  - Cell-specific radiosensitization by gold nanoparticles at megavoltage radiation
      energies.
AB  - PURPOSE: Gold nanoparticles (GNPs) have been shown to cause sensitization with
      kilovoltage (kV) radiation. Differences in the absorption coefficient between
      gold and soft tissue, as a function of photon energy, predict that maximum
      enhancement should occur in the kilovoltage (kV) range, with almost no
      enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are
      not biologically inert, causing oxidative stress and even cell death, suggesting
      a possible biological mechanism for sensitization. The purpose of this study was
      to assess GNP radiosensitization at clinically relevant MV X-ray energies.
      METHODS AND MATERIALS: Cellular uptake, intracellular localization, and
      cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and
      breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic
      survival at kV and MV photon energies and MV electron energies. Intracellular DNA
      double-strand break (DSB) induction and DNA repair were determined and GNP
      chemosensitization was assessed using the radiomimetic agent bleomycin. RESULTS:
      GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with
      nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells,
      radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were
      achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No
      significant effect was observed in L132 or DU145 cells at kV or MV energies (SER
      0.97-1.08). GNP exposure did not increase radiation-induced DSB formation or
      inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231
      cells treated with bleomycin (SER 1.38). CONCLUSIONS: We have demonstrated
      radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization
      was cell-specific with comparable effects at kV and MV energies, no increase in
      DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible
      biological mechanism of radiosensitization.

PMID- 21095076
TI  - Complications of intercostal nerve transfer for brachial plexus reconstruction.
AB  - PURPOSE: Although numerous publications discuss outcomes of intercostal nerve
      transfer for brachial plexus injury, few publications have addressed factors
      associated with intercostal nerve viability or the impact perioperative nerve
      transfer complications have on postoperative nerve function. The purposes of this
      study were to report the results of perioperative intercostal nerve transfer
      complications and to determine whether chest wall trauma is associated with
      damaged or nonviable intercostal nerves. METHODS: All patients who underwent
      intercostal nerve transfer as part of a brachial plexus reconstruction procedure
      as a result of injury were identified. A total of 459 nerves in 153 patients were
      transferred between 1989 and 2007. Most nerves were transferred for use in biceps
      innervation, free-functioning gracilis muscle innervation, or a combination of
      the two. Patient demographics, trauma mechanism, associated injuries,
      intraoperative nerve viability, and perioperative complications were reviewed.
      RESULTS: Complications occurred in 23 of 153 patients. The most common
      complication was pleural tear during nerve elevation, occurring in 14 of 153
      patients. Superficial wound infection occurred in 3 patients, whereas symptomatic
      pleural effusion, acute respiratory distress syndrome, and seroma formation each
      occurred in 2 patients. The rate of complications increased with the number of
      intercostal nerves transferred. Nerves were harvested from previously fractured
      rib levels in 50 patients. Rib fractures were not associated with an increased
      risk of overall complications but were associated with an increased risk of lack
      of nerve viability. In patients with rib fractures, intraoperative nerve
      stimulation revealed 148 of 161 nerves to be functional; these were subsequently
      transferred. In patients with preoperative ipsilateral phrenic nerve palsy, the
      risk of increased complications was marginally significant. CONCLUSIONS: Brachial
      plexus reconstruction using intercostal nerves can be challenging, especially if
      there is antecedent chest wall trauma. Complications were associated with
      increasing numbers of intercostal nerves transferred. Ipsilateral rib fracture
      was adversely associated with intercostal nerve viability; it was not
      significantly associated with complication risk and should not be considered a
      contraindication to transfer. Preoperative phrenic nerve palsy was marginally
      associated with the likelihood of complications but not postoperative respiratory
      dysfunction when associated with intercostal nerve transfer. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Therapeutic IV.

PMID- 21095077
TI  - Pharmacological blockade or genetic knockout of the NOP receptor potentiates the
      rewarding effect of morphine in rats.
AB  - The Nociceptin/OrphaninFQ (NOP) system is believed to be involved in drug abuse
      and addiction. We have recently demonstrated that activation of the NOP receptor,
      by systemic administration of the NOP receptor agonist Ro65-6570, attenuated the
      rewarding effect of various opioids in conditioned place preference (CPP) in rats
      and this attenuating effect was reversed by the NOP receptor antagonist J-113397.
      The present study demonstrates that co-administration of J-113397 (4.64 mg/kg,
      i.p.) during conditioning, facilitates morphine-induced CPP. Moreover, we found
      that NOP receptor knockout rats (oprl1(-/-)) are more sensitive to the rewarding
      effect of morphine than wildtype control rats. Thus, pharmacological or genetic
      inactivation of the NOP system rendered rats more susceptible to the rewarding
      effect of morphine. These findings support the suggestion that the endogenous NOP
      system attenuates the rewarding effect of opioids and therefore offers a
      therapeutic target for the treatment of drug abuse and addiction.

PMID- 21095078
TI  - Attenuation in Leptospira strain collections.

PMID- 21095079
TI  - Cardiovascular and metabolic outcome in 6-8 year old offspring of women with type
      1 diabetes with near-optimal glycaemic control during pregnancy.
AB  - BACKGROUND: High maternal glucose concentrations during diabetic pregnancy may
      lead to health problems in the offspring later in life. We showed in a previous
      nationwide study on pregnancy outcome in type 1 diabetic women that prepregnancy
      care was good and a near-optimal glycaemic control during pregnancy was achieved
      (mean HbA1c 6.2%). AIMS: We investigated to what extent current care and
      treatment of pregnant women with type 1 diabetes were related to cardiovascular
      and metabolic disturbances in the offspring at school age. Additionally, we
      studied the influence of level of maternal glycaemic control, preterm birth and
      neonatal macrosomia (birth weight>p 90). STUDY DESIGN: Observational cohort
      study. SUBJECTS: 6-8 year old offspring of women with type 1 diabetes (ODM,
      n=213) and a control group of children of non-diabetic women (n=79). OUTCOME
      MEASURES: BMI, blood pressure, parameters of fasting glucose regulation and lipid
      metabolism, components of the metabolic syndrome (overweight, hypertension,
      impaired fasting glucose, dyslipidaemia). RESULTS: Parameters of fasting glucose
      regulation and lipid metabolism and the frequency of components of the metabolic
      syndrome did not significantly differ between ODM and controls. Systolic blood
      pressure was slightly higher in ODM. The influence of level of maternal glycaemic
      control, preterm birth and neonatal macrosomia on outcome in ODM was limited.
      CONCLUSIONS: Current care and treatment of pregnant women with type 1 diabetes
      result in cardiovascular and metabolic outcome in the offspring at 6-8 years of
      age that is comparable to that in children of non-diabetic women. Further follow
      up should substantiate these results at later age.

PMID- 21095080
TI  - Reproductive cycle of the elephant.
AB  - The combination of a few factors, including poor captive reproduction, secession
      of importation from the wild and advances in hormone detection and
      ultrasonography, has contributed to the current knowledge on the elephant
      reproductive cycle. Several reproductive features in elephants differ markedly
      from other mammals. These include the urogenital tract anatomy, length and
      structure of the reproductive cycle, the formation of multiple corpora lutea and
      the type and secretion pattern of reproductive hormones. Being 13-18 weeks in
      length, the elephant estrous cycle is the longest amongst all studied non
      seasonal mammals to date. Progesterone increases 1-3 days after ovulation,
      indicating the start of the luteal phase, which lasts 6-12 weeks. This is
      followed by a 4- to 6-week follicular phase that is concluded by two, precisely
      spaced and timed, LH surges. In general, the first, anovulatory LH surge occurs
      exactly 19-21 days before the second, ovulatory surge. Normally, a single
      follicle is ovulated. However, beside a corpus luteum (CL) forming on the site of
      ovulation, multiple accessory CLs can be found on the ovaries. Unlike many other
      species, the predominant progestagen secreted by luteal tissues is not
      progesterone, but rather its 5-alpha-reduced metabolites. The currently known
      aspects of the unique estrous cycle in Asian and African elephants, covering
      estrous behavior, circulating hormones, ultrasonography and anatomy of the
      reproductive organs as well as hormonal manipulation treatment possibilities,
      will be reviewed here.

PMID- 21095081
TI  - Treatment of benign focal epilepsies in children: when and how should be treated?
AB  - Benign focal epilepsies represent almost one-fourth of all childhood epilepsies
      and are a frequent occurrence in clinical practice. They include benign infantile
      seizures (BIS), Panayiotopoulos syndrome (PS), and benign childhood epilepsy with
      centrotemporal spikes (BCECTS) in this order of the onset age. Because the
      prognosis is always excellent in patients with benign focal epilepsies, we must
      consider the risks and benefits of chronic antiepileptic drug (AED)
      administration. AED treatment is usually not recommended for the patients with a
      first attack, but should be considered for those with a second or third attack. A
      choice of AED has been based on the expert opinion. Carbamazepine (CBZ) is
      recommended for both acute and chronic treatment of seizure clusters in patients
      with BIS. Valproic acid (VPA), CBZ or clobazam (CLB) appears to be a first option
      of AED for patients with PS. A common first choice for BCECTS is CBZ in the USA
      and Japan, and VPA in the EU. The treatment period should be as short as possible
      without waiting for EEG normalization, possibly within 2 years after the
      initiation of AED. We must remember that some patients with BCECTS may have an
      "atypical evolution". In conclusion, when and how to treat this benign condition
      should be determined in an individual manner based on the length and frequency of
      seizures, circadian rhythm of the attacks, interictal EEG findings, cognitive and
      behavioral functions in daily life and the attitude of the parents toward seizure
      recurrences and AED side effects.

PMID- 21095082
TI  - [Personal and occupational factors associated with low-back pain in a general
      working population in France].
AB  - BACKGROUND: Low-back pain is a major public health concern because of its
      socioeconomic burden, especially for chronic forms. The purpose of this study was
      to analyse the associations between low-back pain and occupational and personal
      factors, with a special focus on interactions between age and occupational
      exposures. METHODS: The study population comprised a sample of 3958 and 4526
      working women and men aged 30 to 59 derived from a national health survey (2002
      2003 EDS). Low-back pain was assessed using the French version of the Nordic
      questionnaire. Weight, height and smoking status were obtained through interview
      at home. Occupational exposures were self-assessed. The associations between low
      back pain for more than 30 days in the previous year and occupational and
      personal factors were assessed using logistic models. An interaction between age
      and each occupational exposure was studied. RESULTS: In the multivariate models,
      age was the only personal factor significantly associated with low-back pain for
      both genders. The other personal factors studied were significantly associated
      with low-back pain for women only. Handling heavy loads and awkward postures at
      work were strongly associated with low-back pain for both genders (respectively
      OR=1.80 [1.46-2.23] and OR=1.65 [1.34-2.03] for men, and OR=1.65 [1.32-2.06] and
      OR=1.28 [1.04-1.59] for women). A high level of psychological demands at work and
      a low level of decision latitude were also associated with low-back pain for both
      genders (respectively OR=1.22 [1.03-1.46] and OR=1.32 [1.11-1.57] for men, and
      OR=1.31 [1.10-1.56] and OR=1.27 [1.06-1.51] for women). Only the interaction
      between age and awkward postures for men was borderline significant. CONCLUSION:
      This study showed strong associations between occupational exposures and
      persistent/recurrent low-back pain in a general working population in France.
      Targeting these exposures in prevention programs could be useful.

PMID- 21095083
TI  - Use of prior mammograms in the transition to digital mammography: a performance
      and cost analysis.
AB  - Breast screening in Europe is gradually changing from film to digital imaging and
      reporting of cases. In the transition period prior mammograms (from the preceding
      screening round) are films thereby potentially causing difficulties in comparison
      to current digital mammograms. To examine this breast screening performance was
      measured at a digital mammography workstation with prior mammograms displayed in
      different formats, and the associated costs calculated. 160 selected difficult
      cases (41% malignant) were read by eight UK qualified mammography readers in
      three conditions: with film prior mammograms; with digitised prior mammograms; or
      without prior mammograms. Lesion location and probability of malignancy were
      recorded, alongside a decision of whether to recall each case for further tests.
      JAFROC analysis showed a difference between conditions (p=.006); performance with
      prior mammograms in either film or digitised formats was superior to that without
      prior mammograms (p<.05). There was no difference in the performance when the
      prior mammograms were presented in film or digitised form. The number of benign
      or normal cases recalled was 26% higher without prior mammograms than with
      digitised or film prior mammograms (p<.05). This would correspond to an increase
      in recall rate at the study hospital from 4.3% to 5.5% with no associated
      increase in cancer detection rate. The cost of this increase was estimated to be
      L11,581 (?13,666) per 10,000 women screened, which is higher than the cost of
      digitised (L11,114/?13,115), or film display (L6451/?7612) of the prior
      mammograms. It is recommended that, where available, prior mammograms are used in
      the transition to digital breast screening.

PMID- 21095084
TI  - Malate dehydrogenase: a useful phylogenetic marker for the genus Aeromonas.
AB  - The reconstruction of correct genealogies among biological entities, the
      estimation of the divergence time between organisms or the study of the different
      events that occur along evolutionary lineages are not always based on suitable
      genes. For reliable results, it is necessary to look at full-length sequences of
      genes under stabilizing selection (neutral or purifying) and behaving as good
      molecular clocks. In bacteria it has been proved that the malate dehydrogenase
      gene (mdh) can be used to determine the inter- and intraspecies divergence, and
      hence this gene constitutes a potential marker for phylogeny and bacterial
      population genetics. We have sequenced the full-length mdh gene in 36 type and
      reference strains of Aeromonas. The species grouping obtained in the phylogenetic
      tree derived from mdh sequences was in agreement with that currently accepted for
      the genus Aeromonas. The maximum likelihood models applied to our sequences
      indicated that the mdh gene is highly conserved among the Aeromonas species and
      the main evolutionary force acting on it is purifying selection. Only two sites
      under potential diversifying selection were identified (T 108 and S 193). In
      order to determine if these two residues could have an influence on the MDH
      structure, we mapped them in a three-dimensional model constructed from the
      sequence of A. hydrophila using the human mitochondrial MDH as a template. The
      presence of purifying selection together with the linear relationship between
      substitutions and gene divergence makes the mdh an excellent candidate gene for a
      phylogeny of Aeromonas and probably for other bacterial groups.

PMID- 21095085
TI  - Molecular and biochemical diversity of Oenococcus oeni strains isolated during
      spontaneous malolactic fermentation of Malvasia Nera wine.
AB  - The diversity of indigenous Oenococcus oeni strains was investigated by molecular
      and biochemical characterization of isolates from Malvasia Nera wine, an
      economically important red wine of the Salento Region (Apulia, Italy), during
      spontaneous malolactic fermentation (MLF). A total of 82 isolates of this
      species, identified by species-specific PCR and 16S rDNA sequence analysis, was
      molecularly characterized by the amplified fragment length polymorphism (AFLP)
      technique. Three main groups resulted from cluster analysis and showed
      intraspecific homology higher than 50%, and a total of seven subgroups, with
      similarity values ranged from 80% to 98%, were obtained within these groups.
      Enzymatic activities, such as esterase, beta-glucosidase, protease, and the
      consumption rate of l-malic acid, citric acid, acetaldehyde and arginine were
      assessed in the representative strains, according to AFLP analysis. The results
      showed different enzymatic activities and consumption rates of the tested
      metabolites among the strains. No correlation between molecular and biochemical
      data was observed. The evidence of biochemical variability observed among
      Malvasia Nera strains demonstrated that the wine aroma can be modulated depending
      on the strains involved in MLF. Hence, the heterogeneity existing within natural
      O. oeni populations represents an interesting ecological source that can be
      useful for technological purposes.

PMID- 21095086
TI  - Identification of Staphylococcus spp. using (GTG)5-PCR fingerprinting.
AB  - A group of 212 type and reference strains deposited in the Czech Collection of
      Microorganisms (Brno, Czech Republic) and covering 41 Staphylococcus species
      comprising 21 subspecies was characterised using rep-PCR fingerprinting with the
      (GTG)5 primer in order to evaluate this method for identification of
      staphylococci. All strains were typeable using the (GTG)5 primer and generated
      PCR products ranging from 200 to 4500 bp. Numerical analysis of the obtained
      fingerprints revealed (sub)species-specific clustering corresponding with the
      taxonomic position of analysed strains. Taxonomic position of selected strains
      representing the (sub)species that were distributed over multiple rep-PCR
      clusters was verified and confirmed by the partial rpoB gene sequencing.
      Staphylococcus caprae, Staphylococcus equorum, Staphylococcus sciuri,
      Staphylococcus piscifermentans, Staphylococcus xylosus, and Staphylococcus
      saprophyticus revealed heterogeneous fingerprints and each (sub)species was
      distributed over several clusters. However, representatives of the remaining
      Staphylococcus spp. were clearly separated in single (sub)species-specific
      clusters. These results showed rep-PCR with the (GTG)5 primer as a fast and
      reliable method applicable for differentiation and straightforward identification
      of majority of Staphylococcus spp.

PMID- 21095088
TI  - A validated RP-HPLC method for quantitative determination of related impurities
      of ursodeoxycholic acid (API) by refractive index detection.
AB  - An isocratic RP-HPLC method was developed and validated for quantitative
      determination of ursodeoxycholic acid (UDCA) and its related impurities.
      Considering the lower molecular absorptivity of UDCA, refractive index detector
      was used to detect the impurities on a Phenomenex Luna C(18), 150 mm * 4.6 mm, 5
      MUm column. The mobile phase was 0.1% acetic acid/methanol (30:70, v/v) and flow
      rate was 0.8 ml/min. The detector and column temperature was maintained at 40
      degrees C. The method is linear over a range of 0.25-3.5 MUg/ml for all
      impurities and coefficient of correlation (r(2)) was >=0.9945. The accuracy of
      method demonstrated at three levels in the range of 50-150% of the specification
      limit and recoveries were found to be in the range of 97.11-100.75%. The
      precision for all related impurities was below 3.5% R.S.D. The method was applied
      to commercial bulk drug sample for assay purpose.

PMID- 21095087
TI  - Stir bar sorptive extraction of diclofenac from liquid formulations: a proof of
      concept study.
AB  - A new stir bar sorptive extraction (SBSE) technique coupled with HPLC-UV method
      for quantification of diclofenac in pharmaceutical formulations has been
      developed and validated as a proof of concept study. Commercially available
      polydimethylsiloxane stir bars (TwisterTM) were used for method development and
      SBSE extraction (pH, phase ratio, stirring speed, temperature, ionic strength and
      time) and liquid desorption (solvents, desorption method, stirring time etc)
      procedures were optimised. The method was validated as per ICH guidelines and was
      successfully applied for the estimation of diclofenac from three liquid
      formulations viz. Voltarol((r)) Optha single dose eye drops, Voltarol((r)) Ophtha
      multidose eye drops and Voltarol((r)) ampoules. The developed method was found to
      be linear (r=0.9999) over 100-2000ng/ml concentration range with acceptable
      accuracy and precision (tested over three QC concentrations). The SBSE extraction
      recovery of the diclofenac was found to be 70% and the LOD and LOQ of the
      validated method were found to be 16.06 and 48.68ng/ml, respectively.
      Furthermore, a forced degradation study of a diclofenac formulation leading to
      the formation of structurally similar cyclic impurity (indolinone) was carried
      out. The developed extraction method showed comparable results to that of the
      reference method, i.e. method was capable of selectively extracting the
      indolinone and diclofenac from the liquid matrix. Data on inter and intra stir
      bar accuracy and precision further confirmed robustness of the method, supporting
      the multiple re-use of the stir bars.

PMID- 21095089
TI  - Validation of a gas chromatographic method to quantify sesquiterpenes in copaiba
      oils.
AB  - Copaifera species (Leguminoseae) are popularly known as "copaiba" or "copaiva".
      The oleoresins obtained from the trunk of these species have been extensively
      used in folk medicine and are commercialized in Brazil as crude oil and in
      several pharmaceutical and cosmetic products. This work reports a complete
      validated method for the quantification of beta-caryophyllene, alpha-copaene, and
      alpha-humulene in distinct copaiba oleoresins available commercially. Thus,
      essential oil samples (100MUL) were dissolved in 20mL of hexanes containing
      internal standard (1,2,4,5-tetramethylbenzene, 3.0mM) in a 25mL glass flask. A
      1MUL aliquot was injected into the GC-FID system. A fused-silica capillary column
      HP-5, coated with 5% phenyl-methylsiloxane was used for this study. The developed
      method gave a good detection response with linearity in the range of 0.10
      18.74mM. Limits of detection and quantitation variety ranged between 0.003 and
      0.091mM. beta-Caryophyllene, alpha-copaene, and alpha-humulene were recovered in
      a range from 74.71% to 88.31%, displaying RSD lower than 10% and relative errors
      between -11.69% and -25.30%. Therefore, this method could be considered as an
      analytical tool for the quality control of different Copaifera oil samples and
      its products in both cosmetic and pharmaceutical companies.

PMID- 21095091
TI  - Trends in abdominal aortic aneurysm repair in the era of endovascular technology
      in Ontario.

PMID- 21095090
TI  - Antithrombotic effect of grape seed proanthocyanidins extract in a rat model of
      deep vein thrombosis.
AB  - OBJECTIVE: Proanthocyanidins are abundantly found in grape seeds and have been
      suggested to inhibit the pathogenesis of systemic diseases. We investigated the
      antithrombotic effects of proanthocyanidins in a rat model of deep vein
      thrombosis (DVT) and examined the underlying mechanisms. METHODS: DVT was induced
      in rat model by inferior vena cava (IVC) ligation. Grape seed proanthocyanidins
      extract (GSPE, 400 mg/kg/d) dissolved in saline (2 mL) was orally administered to
      the experimental rats. Control rats were administrated saline (2 mL) only. The
      thrombi were harvested and weighed. The IVC was analyzed histologically and by
      transmission electron microscopy. The cytokines interleukin (IL)-6, IL-8, and
      tumor necrosis factor-alpha (TNF-alpha) were detected by enzyme-linked
      immunosorbent assay. Expression of cellular adhesion molecules (CAMs) in thrombi
      was examined by Western blot. RESULTS: GSPE significantly reduced thrombus length
      and weight (P < .01) and protected the integrity of the endothelium. GSPE
      inhibited thrombogenesis-promoting factors P-selectin, von Willebrand factor, and
      CAMs, and promoted thrombogenesis-demoting factors CD34, vascular endothelial
      growth factor receptor-2, and ADAMTS13 (a disintegrin and metalloproteinase with
      a thrombospondin type one motif, member 13). Compared with the control, GSPE
      significantly lowered the cytokines IL-6 (74.19 +/- 13.86 vs 189.54 +/- 43.76
      pg/mL; P < .01), IL-8 (80.71 +/- 21.42 vs 164.56 +/- 39.54 pg/mL; P < .01), and
      TNF-alpha (43.11 +/- 17.58 vs 231.84 +/- 84.11 pg/mL; P < .01). CONCLUSIONS: GSPE
      significantly inhibited the propagation of thrombus induced by IVC ligation in a
      rat model. The antithrombotic properties of proanthocyanidins are likely to be
      directly associated with endothelial protection and regeneration, platelet
      aggregation, and inhibition of inflammatory cell and thrombus adhesion. Thus,
      proanthocyanidins may have a clinical application in DVT treatment.

PMID- 21095093
TI  - Transradial iliac artery intervention with dual downstream embolic protection.
AB  - We report a case of a thrombotic common iliac lesion with concern for elevated
      risk of downstream embolization during intervention. In this case, a transradial
      approach enabled the novel, simultaneous deployment of two embolic protection
      devices, one in the internal iliac artery and the other in the common femoral
      artery, for complete downstream protection during intervention. An endovascular
      stent, which accommodates a 0.035-inch wire lumen, was able to be delivered over
      both 0.014-inch protection device wires simultaneously and was successfully
      deployed with evidence of captured embolic material.

PMID- 21095092
TI  - Predictors of early and late mortality following open extent IV thoracoabdominal
      aortic aneurysm repair in a large contemporary single-center experience.
AB  - OBJECTIVE: The primary purpose of this study was to examine outcomes following
      open repair of extent IV thoracoabdominal aortic aneurysms (TAAAs) at a single
      university hospital. As a secondary aim, comparison was made to patients who
      underwent open abdominal aortic aneurysm (AAA) repair with supraceliac clamping
      but without left renal artery bypass to assess the effect of left renal artery
      bypass on outcomes. METHODS: Patients undergoing open extent IV TAAA repair from
      1998 to 2008 were identified (n = 108). Primary outcomes were 30-day and long
      term survival. Secondary outcomes were major complication, renal failure, and
      postoperative change in renal function. A second analysis was performed,
      comparing patients undergoing extent IV TAAA repair with patients undergoing AAA
      repair with supraceliac clamping but without left renal artery bypass (n = 50).
      RESULTS: Eighty-three men (76.9%) and 25 women (23.1%), with a mean age of 72.9
      years, underwent open extent IV TAAA repair. Nine patients (8.3%) were ruptured.
      Mean aneurysm maximal diameter was 6.5 +/- 1.3 cm. Supraceliac and left renal
      ischemic times were 22.9 +/- 9.3 and 40.6 +/- 16.2 minutes, respectively. Six
      patients (5.6%) died at 30 days. The only predictor of 30-day mortality was
      decreased preoperative estimated glomerular filtration rate (eGFR) (P = .044 by
      multivariate analysis; and P = .011 by univariate analysis). One-year and 5-year
      survival rates were 87% and 50%, respectively. Patients with a history of
      cerebrovascular disease (P = .001) and postoperative renal insufficiency (P =
      .034) had increased long-term mortality by log-rank test. Twenty-five (25.3%)
      patients sustained a postoperative decrease in renal function, while 19 (19.2%)
      patients had an improvement in renal function. There was no difference in 30-day
      mortality (5.6% vs 6.0%; P = 1.000), 5-year survival (50% vs 48%; P = .886),
      major complications (37.0% vs 38.0%; P = 1.000), renal failure (6.1% vs 0%; P =
      .215), or postoperative change in renal function, in patients undergoing extent
      IV TAAA repair vs AAA repair with supraceliac clamping but without left renal
      artery bypass. CONCLUSIONS: Open extent IV TAAA repair can be performed with low
      morbidity and mortality rates. The performance of left renal artery bypass does
      not appear to contribute to the morbidity and mortality of extent IV TAAA repair.
      While decreased preoperative eGFR appears to increase the risk of 30-day
      mortality, a history of cerebrovascular disease and postoperative renal
      insufficiency appear to increase the risk of long-term mortality. Finally, open
      extent IV TAAA repair not uncommonly improves renal function.

PMID- 21095094
TI  - Axillary nodal yields: a comparison between primary clearance and completion
      clearance after sentinel lymph node biopsy in the management of breast cancer.
AB  - AIMS: Axillary nodal status is the most important prognostic indicator which in
      turn influences adjuvant therapy and long term outcomes. The aim of this study
      was to compare total nodal yields from primary axillary lymph node dissection
      (pALND) with completion ALND after a cancer positive SLNB: either concurrently
      (cALND) following intra-operative assessment (IOA) of the SLN's or as a delayed
      procedure (dALND) when the SLN was found to be cancer positive on post-operative
      histological examination. METHODS: All axillary procedures performed between May
      2006 and September 2009 were identified from a prospective database and
      categorised into four groups: SLNB with no further axillary surgery, pALND, cALND
      and dALND. Total nodal yield was the sum of SLN/s and ALND yields. RESULTS: Of
      1025 axillary procedures, ALND accounted for 332 (32.4%) of which 207 (62.3%)
      underwent pALND, 43 (12.9%) cALND, and 82 (24.6%) dALND. Median nodal yields were
      15.0, 16.0 and 14.5 respectively (p = 0.3). CONCLUSION: Total nodal yields for
      primary, concurrent and delayed ALND were comparable suggesting completion dALND
      performed as a second operation does not compromise axillary staging.

PMID- 21095095
TI  - Altered expression of HSP27 and HSP70 in distal oesophageal mucosa in patients
      with gastro-oesophageal reflux disease subjected to fundoplication.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a risk factor for
      oesophageal adenocarcinoma. Although fundoplication cures reflux symptoms and
      oesophagitis, it remains controversial whether it is capable of preventing the
      development of oesophageal adenocarcinoma. Hsp27 and Hsp70 are associated with
      the development of cancer, whereas the effect of fundoplication on them is not
      known. METHODS: The expression of Hsp27 and Hsp70 was assessed semiquantitatively
      from biopsies of oesophageal mucosa for a prospective cohort of 19 patients with
      GERD treated with fundoplication and 7 controls without GERD. Upper
      gastrointestinal endoscopy with biopsies from the oesophagogastric junction (EGJ)
      and the distal and proximal oesophagus were performed preoperatively (19
      patients) and after recovery from GERD at 6 (19 patients) and 48 months (16
      patients) postoperatively. RESULTS: The expressions of both Hsp27 (p = 0.001) and
      Hsp70 (p = 0.002) in the distal oesophagus were lower in patients preoperatively
      and at 48 months postoperatively (p < 0.001 for both) than in controls. The
      patients' Hsp27 and Hsp70 levels were lower preoperatively in the proximal
      oesophagus (p = 0.048 for both) than in controls. Both Hsp27 (p = 0.002) and
      Hsp70 (p = 0.003) were lower in the distal oesophagus preoperatively and at 48
      months postoperatively (p = 0.003 for Hsp27, p = 0.004 for Hsp70) than in the
      proximal oesophagus. CONCLUSIONS: Our results indicate that there may be some
      factor interfering with the mucosal defence system of the distal oesophagus in
      GERD that is uninfluenced by fundoplication and not associated with the acid
      reflux-normalizing effect.

PMID- 21095096
TI  - Assessment of body composition using whole body air-displacement plethysmography
      in children with and without developmental coordination disorder.
AB  - Developmental coordination disorder (DCD) is a neuro-developmental disorder
      characterized by poor fine and/or gross motor coordination. Children with DCD are
      hypothesized to be at increased risk for overweight and obesity from inactivity
      due to their motor coordination problems. Although previous studies have found
      evidence to support this hypothesis, their reliance on field-based measures, most
      notably body mass index (BMI), to determine body composition is problematic.
      Moreover, there has been no research to date that has examined whether THERE ARE
      differences in lean tissue mass between children with and without coordination.
      Differences in muscle mass, the main component of lean tissue, may be a
      contributing factor to both coordination problems and the development of
      overweight and obesity, but has only been indirectly examined at this time. In
      this study, whole-body air displacement using a dual chamber plethysmograph was
      used to estimate fat mass, fat free mass and body fat in children with probable
      DCD (pDCD) and a group of typically developing children. Consistent with previous
      research using field-based assessments of relative body weight, the results show
      that children with pDCD have much higher body fat than their peers, and that this
      difference increases with the severity of observed motor coordination
      difficulties. There was no difference in lean tissue mass between groups. The
      demonstration of an association between pDCD and body fat using a more sensitive
      measure of body composition, and evidence showing a dose-response in this
      relationship, further supports the hypothesis that DCD may be a risk factor for
      obesity in children.

PMID- 21095097
TI  - Influence of motivating operations and discriminative stimuli on challenging
      behavior maintained by positive reinforcement.
AB  - We examined the effects of an establishing operation (EO) and abolishing
      operation (AO) on stimulus control of challenging behavior. Two participants with
      developmental disabilities and challenging behavior participated. In Phase I, a
      functional analysis was conducted to identify the consequences maintaining
      challenging behavior. In Phase II, a discrimination between SD and SDelta was
      trained. In Phase III, pre-session MOs (i.e., EO and AO conditions) were arranged
      to assess their effects on challenging behavior. Finally in Phase IV, in addition
      to manipulating pre-session MOs the challenging behavior was evaluated under
      extinction in both SD and SDelta conditions. Results indicated that in the
      context of extinction when pre-session EO and AO conditions were manipulated,
      responding not only became differentiated but was higher in both SD and SDelta
      conditions in the pre-session EO condition when compared to the pre-session AO
      condition.

PMID- 21095098
TI  - Quasi-objective nonlinear principal component analysis.
AB  - By means of mathematical analysis and numerical experimentation, this study shows
      that the problems of non-uniqueness of solutions and data over-fitting, that
      plague the multilayer feedforward neural network for NonLinear Principal
      Component Analysis (NLPCA), are caused by inappropriate architecture of the
      neural network. A simplified two-hidden-layer feedforward neural network, which
      has no encoding layer and no bias term in the mathematical definitions of
      bottleneck and output neurons, is proposed to conduct NLPCA. This new, compact
      NLPCA model alleviates the aforementioned problems encountered when using the
      more complex neural network architecture for NLPCA. The numerical experiments are
      based on a data set generated from a well-known nonlinear system, the Lorenz
      chaotic attractor. Given the same number of bottleneck neurons or reduced
      dimensions, the compact NLPCA model effectively characterizes and represents the
      Lorenz attractor with significantly fewer parameters than the relevant three
      hidden-layer feedforward neural network for NLPCA.

PMID- 21095099
TI  - Assessment of myocardial deformation in children using Digital Imaging and
      Communications in Medicine (DICOM) data and vendor independent speckle tracking
      software.
AB  - BACKGROUND: Analysis of myocardial deformation from data stored in Digital
      Imaging and Communications in Medicine format using vendor-independent software
      may be useful for clinical and research purposes but has not been evaluated in
      children. METHODS: Grayscale images were prospectively acquired on Vivid 7 (GE
      Healthcare) and iE33 (Philips Medical Systems) ultrasound systems in 49 children.
      Digital Imaging and Communications in Medicine and raw data were analyzed using
      vendor-independent software (Cardiac Performance Analysis, Tomtec Imaging
      Systems) and vendor-specific software (EchoPAC and QLAB) and results compared. In
      addition, vendor-independent software using images at 30 frames/sec were compared
      with images at the higher acquisition frame rate. RESULTS: Measurement of short
      axis radial and circumferential strain (epsilon) and apical four-chamber
      longitudinal epsilon by vendor-independent software was possible in >92% of the
      children. Intraobserver and interobserver coefficients of variation for global
      circumferential and longitudinal epsilon ranged from 7.1% to 15.3% and for radial
      epsilon from 23.9% to 30.2%. Strain values were somewhat higher when using GE
      images at acquisition frame rates compared with epsilon values using GE images
      stored at 30 frames/sec. Strain values obtained by vendor-independent software
      were comparable with those obtained by vendor-specific software for longitudinal
      epsilon and higher for circumferential epsilon. Radial epsilon values obtained by
      vendor-independent software were lower than epsilon values by EchoPAC and higher
      than epsilon values by QLAB. CONCLUSIONS: Vendor-independent software-derived
      epsilon is feasible and potentially valuable for measuring myocardial deformation
      in research and in multicenter studies using images from different ultrasound
      systems, especially for longitudinal deformation. However, a systematic bias for
      circumferential epsilon and a high variability in radial epsilon measurements
      remain concerns.

PMID- 21095101
TI  - Uncommon complication of facial fractures.
AB  - Vascular complications after head and neck surgical procedures are rare but can
      life-threatening. A pseudoaneurysm may appear weeks or months after the initial
      injury and may be difficult to diagnose. The authors report the case of a 43-year
      old man involved in a motor vehicle accident presenting with multiple facial
      fractures, which after surgical treatment presented episodes of bleeding. After
      an angiography was performed, a pseudoaneurysm of the facial artery was detected.
      The patient later underwent endovascular embolization and had a satisfactory
      resolution.

PMID- 21095100
TI  - Limited sufficiency of antigen presentation by dendritic cells in models of
      central nervous system autoimmunity.
AB  - Experimental autoimmune encephalomyelitis (EAE), a model for the human disease
      multiple sclerosis (MS), is dependent upon the activation and effector functions
      of autoreactive CD4 T cells. Multiple interactions between CD4 T cells and major
      histocompatibility class II (MHCII)+ antigen presenting cells (APCs) must occur
      in both the periphery and central nervous system (CNS) to elicit autoimmunity.
      The identity of the MHCII+ APCs involved throughout this process remains in
      question. We investigated which APC in the periphery and CNS mediates disease
      using transgenic mice with MHCII expression restricted to dendritic cells (DCs).
      MHCII expression restricted to DCs results in normal susceptibility to peptide
      mediated EAE. Indeed, radiation-sensitive bone marrow-derived DCs were sufficient
      for all APC functions during peptide-induced disease. However, DCs alone were
      inefficient at promoting disease after immunization with the myelin protein
      myelin oligodendrocyte glycoprotein (MOG), even in the presence of MHCII
      deficient B cells. Consistent with a defect in disease induction following
      protein immunization, antigen presentation by DCs alone was incapable of
      mediating spontaneous optic neuritis. These results indicate that DCs are capable
      of perpetuating CNS-targeted autoimmunity when antigens are readily available,
      but other APCs are required to efficiently initiate pathogenic cognate CD4 T cell
      responses.

PMID- 21095102
TI  - Ultrasound guided wire localisation to aid surgical biopsy of impalpable parotid
      oncocytoma.
AB  - Ultrasound guided wire localisation (UGWL) is an effective way of helping a
      surgeon find an impalpable lesion but its use in the head and neck has only
      recently been described. The authors present an unusual case of bilateral multi
      focal parotid oncocytoma, in which UGWL was combined with extracapsular
      dissection to obtain an impalpable lesion for histological examination following
      initial equivocal core biopsy.

PMID- 21095103
TI  - Digital three-dimensional image fusion processes for planning and evaluating
      orthodontics and orthognathic surgery. A systematic review.
AB  - The three important tissue groups in orthognathic surgery (facial soft tissues,
      facial skeleton and dentition) can be referred to as a triad. This triad plays a
      decisive role in planning orthognathic surgery. Technological developments have
      led to the development of different three-dimensional (3D) technologies such as
      multiplanar CT and MRI scanning, 3D photography modalities and surface scanning.
      An objective method to predict surgical and orthodontic outcome should be
      established based on the integration of structural (soft tissue envelope, facial
      skeleton and dentition) and photographic 3D images. None of the craniofacial
      imaging techniques can capture the complete triad with optimal quality. This can
      only be achieved by 'image fusion' of different imaging techniques to create a 3D
      virtual head that can display all triad elements. A systematic search of current
      literature on image fusion in the craniofacial area was performed. 15 articles
      were found describing 3D digital image fusion models of two or more different
      imaging techniques for orthodontics and orthognathic surgery. From these articles
      it is concluded, that image fusion and especially the 3D virtual head are
      accurate and realistic tools for documentation, analysis, treatment planning and
      long term follow up. This may provide an accurate and realistic prediction model.

PMID- 21095104
TI  - Transition and remission in adolescents at ultra-high risk for psychosis.
AB  - BACKGROUND: Future success of early intervention initiatives to prevent the onset
      of psychosis will rely on the validity of methods to predict clinical outcome.
      Proper identification is particularly essential for young adolescents, as
      psychotic-like symptoms are often transitory during this period and mislabeling
      can lead to early stigmatization and unnecessary treatment. This article presents
      results from a prospective, naturalistic 2-year follow-up study of a cohort of
      young adolescents putatively at ultra-high risk (UHR) for psychosis. METHODS:
      Seventy-two adolescents between 12 and 18years were recruited, fulfilling either
      UHR criteria or the basic symptom-based criterion cognitive disturbances
      (COGDIS). Incidence of transition as well as the remission rate from UHR status
      was calculated. Individuals who made a transition (UHR-P) were compared to those
      who did not (UHR-NP) and to those who remitted (UHR-R) on socio-demographic and
      clinical characteristics. RESULTS: Fifty-seven UHR individuals completed the 2
      year follow-up assessment. The confirmed transition rate was 15.6% and 35.3%
      still met UHR criteria. The remaining 49.1% had remitted from an initial UHR
      status. The UHR subgroups did not differ on socio-demographic or clinical
      variables at baseline. CONCLUSIONS: Half of young adolescents meeting UHR
      criteria continue to experience prodromal or psychotic symptoms after 2 years.
      However, they are at least three times more likely to have remitted from their
      UHR status than to have made a transition to psychosis. In addition, baseline
      characteristics are not indicative of clinical outcome at follow-up. Our results
      emphasize the need for further improvement and stratification of relative risk
      factors for psychosis.

PMID- 21095105
TI  - Correlated structural and functional brain abnormalities in the default mode
      network in schizophrenia patients.
AB  - BACKGROUND: There is increasing evidence of default mode network (DMN)
      dysfunction in schizophrenia. It has also been suggested that brain structural
      changes are maximal in a medial frontal area which overlaps with the anterior
      midline node of this network. METHODS: Brain deactivations were examined in 14
      schizophrenic patients and 14 controls during performance of two tasks requiring
      identification or labelling of facial emotions. Grey matter and white matter
      volumes were compared using voxel-based morphometry. RESULTS: Relative to the
      controls, the schizophrenic patients showed failure to deactivate in the anterior
      and posterior midline nodes of the default mode network, as well as other areas
      considered to be part of the network. Grey matter volume reductions in the
      patients were found in medial cortical regions which overlapped with the same
      parts of the network. The functional and structural changes showed significant
      correlations in a number of medial cortical areas. CONCLUSIONS: Failure of
      deactivation in the default mode network is seen in schizophrenic patients when
      they perform facial emotion tasks. This failure is more extensive than that seen
      during performance of working memory tasks. The study also supports recent
      findings of brain structural changes in schizophrenia in the territory of the
      default mode network.

PMID- 21095106
TI  - Significant correlation of serum IL-22 levels with CCL17 levels in atopic
      dermatitis.

PMID- 21095107
TI  - Efficacy of hesperidin on plasma, heart and liver tissue lipids in rats subjected
      to isoproterenol-induced cardiotoxicity.
AB  - The present study examines the preventive role of hesperidin (HDN) on plasma,
      cardiac and hepatic lipids in isoproterenol (ISO)-induced rats. Myocardial injury
      was induced by subcutaneous injection of isoproterenol hydrochloride (85 mg/kg
      BW) twice at an interval of 24 h, for two consecutive days. HDN was administered
      by post-orally at a dose of 200 mg/kg BW. The results showed increased levels of
      plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density
      lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA) and
      phospholipids (PL) and decreased level of high density lipoprotein-cholesterol
      (HDL-C) in ISO-induced rats. ISO rats also showed an increase in cholesterol, TG
      and FFA and decrease in PL levels in the heart and liver tissues. HDN treatment
      brought the above parameters towards normal level. This experiment shows that HDN
      possesses hypolipidemic effect in ISO-induced rats.

PMID- 21095108
TI  - Toxic effects of citrinin on the male reproductive system in mice.
AB  - This study investigated the effects of citrinin (CTN) on male mouse reproductive
      organs. Adult male mice were exposed to intraperitoneal injection of CTN at 0
      6.25 mg/kg body weight daily for 7 days, and then mated with sexually mature
      untreated female mice. Reproductive organ relative weights, semen quality, serum
      testosterone concentrations and fertility of treated mice were assessed. CTN
      significantly increased relative weights of the testes, epididymis, seminal
      vesicle and preputial gland, increased the number of abnormal spermatozoa and
      decreased the number of live spermatozoa. A significantly lower pregnancy rate
      was observed when females were mated with CTN-exposed males. The histological
      results indicated that distance of testicular seminiferus tubule increased. The
      sperm count and serum testosterone concentrations were significantly reduced in a
      dose-dependent manner in mice treated with CTN. The results suggest that CTN has
      adverse effects on the reproductive system of adult male mice.

PMID- 21095109
TI  - Genistein effects on haematoimmune cells in a newly developed alternative
      toxicological model.
AB  - Unexpected, sometimes opposite effects of dietary isoflavonic phytoestrogens on
      immunity may suggest that classical mammalian toxicological assays are not
      entirely suitable for preclinical safety tests of these compounds. We evaluated a
      new alternative model of haemocytes of Egyptian cotton worm in vivo following
      genistein administration. Genistein induced significant changes in nucleolar
      morphology of haemocytes but did not influence their counts and nucleolar
      indices. The results indicate that genistein does not affect proliferation and
      differentiation of normal cells but potentiates their immuno-competence. Egyptian
      cotton worm larvae seem to be the new alternative biomodel for immunological
      screening.

PMID- 21095110
TI  - Basophils as APC in Th2 response in allergic inflammation and parasite infection.
AB  - Basophils are important effector cells, which contribute to protection against
      helminths and execute proinflammatory effector function during allergic
      inflammation. Basophils are also regulators of Th2 responses in helminth-infected
      hosts and in allergen-injected animals. Recently, three groups using different
      experimental systems have shown that basophils are antigen-presenting cells
      (APC), which induce Th2 cells both in vitro and in vivo. Basophils express MHC
      class II and CD80/86, have the potential to take-up and process protein antigen
      (Ag), particularly Ag-IgE complexes, and to present peptide with MHC class II and
      produce IL-4. However, relevance of basophils as Th2 cell-inducing APC in vivo
      has been challenged by several recent reports that favor the concept that
      basophils and DC cooperate or basophils merely amplify DC-driven Th2 cell
      differentiation. In this review, I summarize and discuss the data on the role of
      basophils as Th2 cell-inducing APC in allergy and parasite infection.

PMID- 21095111
TI  - Bacterial polarity.
AB  - Many recent studies have revealed exquisite subcellular localization of proteins,
      DNA, and other molecules within bacterial cells, giving credence to the concept
      of prokaryotic anatomy. Common sites for localized components are the poles of
      rod-shaped cells, which are dynamically modified in composition and function in
      order to control cellular physiology. An impressively diverse array of mechanisms
      underlies bacterial polarity, including oscillatory systems, phospho-signaling
      pathways, the sensing of membrane curvature, and the integration of cell cycle
      regulators with polar maturation.

PMID- 21095112
TI  - Monitoring the growth and drug susceptibility of individual bacteria using
      asynchronous magnetic bead rotation sensors.
AB  - Continuous growth of individual bacteria has been previously studied by direct
      observation using optical imaging. However, optical microscopy studies are
      inherently diffraction limited and limited in the number of individual cells that
      can be continuously monitored. Here we report on the use of the asynchronous
      magnetic bead rotation (AMBR) sensor, which is not diffraction limited. The AMBR
      sensor allows for the measurement of nanoscale growth dynamics of individual
      bacterial cells, over multiple generations. This torque-based magnetic bead
      sensor monitors variations in drag caused by the attachment and growth of a
      single bacterial cell. In this manner, we observed the growth and division of
      individual Escherichia coli, with 80-nm sensitivity to the cell length. Over the
      life cycle of a cell, we observed up to a 300% increase in the rotational period
      of the biosensor due to increased cell volume. In addition, we observed single
      bacterial cell growth response to antibiotics. This work demonstrates the non
      microscopy limited AMBR biosensor for monitoring individual cell growth dynamics,
      including cell elongation, generation time, lag time, and division, as well as
      their sensitivity to antibiotics.

PMID- 21095113
TI  - Measuring growth rate in high-throughput growth phenotyping.
AB  - Growth rate is an important variable and parameter in biology with a central role
      in evolutionary, functional genomics, and systems biology studies. In this review
      the pros and cons of the different technologies presently available for high
      throughput measurements of growth rate are discussed. Growth rate can be measured
      in liquid microcultivation of individual strains, in competition between strains,
      as growing colonies on agar, as division of individual cells, and estimated from
      molecular reporters. Irrespective of methodology, statistical issues such as
      spatial biases and batch effects are crucial to investigate and correct for to
      ensure low false discovery rates. The rather low correlations between studies
      indicate that cross-laboratory comparison and standardization are pressing issue
      to assure high-quality and comparable growth-rate data.

PMID- 21095114
TI  - Immediate effect of foot orthoses on plantar force timing during running: A
      repeated measures study.
AB  - BACKGROUND: Despite evidence supporting the use of foot orthoses in the
      prevention and treatment of several running related conditions, the physical
      effects of these devices during running is currently unclear. This limitation has
      clinical consequences in relation to dispensing foot orthoses, as the presumed
      biomechanical action may not be produced as intended. The aim of this study was
      therefore to investigate the effect of foot orthoses on plantar force timing
      during running. METHODS: A laboratory study with a repeated measures design was
      conducted with subjects (n = 20) running on a treadmill while wearing an in-shoe
      force measurement device. The effect of two types of prefabricated foot orthoses
      (ProthoticTM S and ProthoticTM W) on plantar force timing beneath the rearfoot
      and forefoot was observed in comparison to a control condition. RESULTS: No
      statistically significant effects between conditions were found for rearfoot
      variables. In contrast, peak forefoot force occurred earlier and the duration of
      forefoot off-loading was extended in both orthosis conditions (P < 0.05, d > 0.9)
      compared with control. The ProthoticTM S was found to have a larger effect on
      plantar force timing beneath the forefoot, and also decreased the duration of
      forefoot loading (P = 0.04, d = 0.8). CONCLUSION: The foot orthoses used in this
      study were observed to have systematic effects on plantar force timing during
      running. The findings of this study may be used to guide future research in this
      field, as the clinical importance of these effects remains unclear.

PMID- 21095115
TI  - Prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of
      children with acute lymphoblastic leukaemia (ALL) treated without cranial
      irradiation: results of European Organization for Research and Treatment of
      Cancer (EORTC) Children Leukemia Group study 58881.
AB  - AIM OF THE STUDY: To evaluate the prognostic significance of the initial cerebro
      spinal fluid (CSF) involvement of children with ALL enrolled from 1989 to 1996 in
      the EORTC 58881 trial. PATIENTS AND METHODS: Patients (2025) were categorised
      according to initial central nervous system (CNS) status: CNS-1 (CNS negative,
      n=1866), CNS-2 (<5 leucocytes/mm(3), CSF with blasts, n=50), CNS-3 (CNS positive,
      n=49), TLP+ (TLP with blasts, n=60). CNS-directed therapy consisted in
      intravenous (i.v.) methotrexate (5 g/sqm) in 4-10 courses, and intrathecal
      methotrexate injections (10-20), according to CNS status. Cranial irradiation was
      omitted in all patients. RESULTS: In the CNS1, TLP+, CNS2 and CNS3 group the 8
      year EFS rate (SE%) was 69.7% (1.1%), 68.8% (6.2%), 71.3% (6.5%) and 68.3%
      (6.2%), respectively. The 8-year incidence of isolated CNS relapse (SE%) was 3.4%
      (0.4%), 1.7% (1.7%), 6.1% (3.5%) and 9.4% (4.5%), respectively, whereas the 8
      year isolated or combined CNS relapse incidence was 7.6% (0.6%), 3.5% (2.4%),
      10.2% (4.4%) and 11.7% (5.0%), respectively. Patients with CSF blasts had a
      higher rate of initial bad risk features. Multivariate analysis indicated that
      presence of blasts in the CSF had no prognostic value: (i) for EFS and OS; (ii)
      for isolated and isolated or combined CNS relapse; WBC count<25 * 10(9)/L and
      Medac E-coli asparaginase treatment were each related to a lower CNS relapse
      risk. CONCLUSIONS: The presence of initial CNS involvement has no prognostic
      significance in EORTC 58881. Intensification of CNS-directed chemotherapy,
      without CNS radiation, is an effective treatment of initial meningeal leukaemic
      involvement.

PMID- 21095116
TI  - 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating
      factor to reduce the incidence of chemotherapy-induced febrile neutropenia in
      adult patients with lymphoproliferative disorders and solid tumours.
AB  - Chemotherapy-induced neutropenia is a major risk factor for infection-related
      morbidity and mortality and also a significant dose-limiting toxicity in cancer
      treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN)
      during chemotherapy frequently receive dose reductions and/or delays to their
      chemotherapy. This may impact the success of treatment, particularly when
      treatment intent is either curative or to prolong survival. In Europe,
      prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such
      as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is
      available to reduce the risk of chemotherapy-induced neutropenia. However, the
      use of G-CSF prophylactic treatment varies widely in clinical practice, both in
      the timing of therapy and in the patients to whom it is offered. The need for
      generally applicable, European-focused guidelines led to the formation of a
      European Guidelines Working Party by the European Organisation for Research and
      Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use
      of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new
      systematic literature review has been undertaken to ensure that recommendations
      are current and provide guidance on clinical practice in Europe. We recommend
      that patient-related adverse risk factors, such as elderly age (>=65 years) and
      neutrophil count be evaluated in the overall assessment of FN risk before
      administering each cycle of chemotherapy. It is important that after a previous
      episode of FN, patients receive prophylactic administration of G-CSF in
      subsequent cycles. We provide an expanded list of common chemotherapy regimens
      considered to have a high (>=20%) or intermediate (10-20%) risk of FN.
      Prophylactic G-CSF continues to be recommended in patients receiving a
      chemotherapy regimen with high risk of FN. When using a chemotherapy regimen
      associated with FN in 10-20% of patients, particular attention should be given to
      patient-related risk factors that may increase the overall risk of FN. In
      situations where dose-dense or dose-intense chemotherapy strategies have survival
      benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in
      chemotherapy dose intensity or density are known to be associated with a poor
      prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy.
      Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have
      clinical efficacy and we recommend the use of any of these agents to prevent FN
      and FN-related complications where indicated. Filgrastim biosimilars are also
      approved for use in Europe. While other forms of G-CSF, including biosimilars,
      are administered by a course of daily injections, pegfilgrastim allows once-per
      cycle administration. Choice of formulation remains a matter for individual
      clinical judgement. Evidence from multiple low level studies derived from audit
      data and clinical practice suggests that some patients receive suboptimal daily G
      CSFs; the use of pegfilgrastim may avoid this problem.

PMID- 21095117
TI  - Composting of bio-waste, aerobic and anaerobic sludges--effect of feedstock on
      the process and quality of compost.
AB  - In-vessel composting of three stocks with originally different degree of organic
      matter degradation was conducted for: (1) kitchen source-separated bio-waste
      (BW), (2) aerobic (AS) as well as (3) anaerobic sludges (AnS) from municipal
      wastewater treatment plant. Composting experiment lasted over a year. The highest
      activity of the process was in the BW compost. It was implied by the highest
      temperature, CO(2) release, ammonification and nitrification, intensive
      accumulation and removal of low-weight carboxylic acids (water- and NaOH
      extractable). Between the sludges higher mineralization and CO2 release was in
      AnS, while ammonification and nitrification were higher in AS compost; no
      significant difference between sludge composts was noticed for dynamics of pH,
      conductivity, concentrations of LWCA, and some nutrient compounds and heavy
      metals. Nitrogen content of the final compost increased in BW, but decreased in
      AS and AnS. Phytotoxicity of Lepidium sativum was eliminated faster in sludge
      composts compared to BW compost.

PMID- 21095118
TI  - Bacterial community dynamics in a functionally stable pilot-scale wastewater
      treatment plant.
AB  - To determine whether functional stability was correlated with a stable microbial
      community structure in a functionally stable pilot-scale wastewater treatment
      plant, bacterial communities in the system were monitored over a one-year period.
      Bacterial community dynamics was characterized by the terminal restriction
      fragment length polymorphism (T-RFLP) of 16S rRNA genes. During the study period,
      the effluent BOD concentrations were very stable, with the average BOD
      concentration below 10 mg/L. The effluent TN concentrations were always below 20
      mg/L, except for the first 40 days. T-RFLP results showed that, during the test
      period, the bacterial community structures were not stable, with an average
      change rate (every 15 days) of 20.4%+/-11.2%. Based on Lorenz distribution
      curves, it was observed that 20% of the species corresponded with 40-77% of
      cumulative relative abundances. Results clearly revealed that, in the pilot-scale
      wastewater treatment plant, functional stability did not correlate with stable
      bacterial communities.

PMID- 21095119
TI  - Development of a yeast strain for xylitol production without hydrolysate
      detoxification as part of the integration of co-product generation within the
      lignocellulosic ethanol process.
AB  - The present study verified an applicable technology of xylitol bioconversion as
      part of the integration of co-product generation within second-generation
      bioethanol processes. A newly isolated yeast strain, Candida tropicalis JH030,
      was shown to have a capacity for xylitol production from hemicellulosic
      hydrolysate without detoxification. The yeast gives a promising xylitol yield of
      0.71 g(p) g(s)(-1) from non-detoxified rice straw hydrolysate that had been
      prepared by the dilute acid pretreatment under severe conditions. The yeast's
      capacity was also found to be practicable with various other raw materials, such
      as sugarcane bagasse, silvergrass, napiergrass and pineapple peel. The lack of a
      need to hydrolysate detoxification enhances the potential of this newly isolated
      yeast for xylitol production and this, in turn, has the capacity to improve
      economics of lignocellulosic ethanol production.

PMID- 21095121
TI  - Molecular modeling and UV-vis spectroscopic studies on the mechanism of action of
      reversed chloroquine (RCQ).
AB  - Reversed chloroquine (RCQ) is a multiple ligand compound active against
      chloroquine-sensitive and resistant falciparum malaria. It is composed by a 4
      aminoquinoline moiety (like that present in chloroquine (CQ)) joined to
      imipramine (IMP), a modulating agent that also showed intrinsic antiplasmodial
      activity against Brazilian Plasmodium falciparum isolates resistant to CQ.
      Molecular modeling and ultraviolet-visible spectroscopy (UV-vis) studies strongly
      suggest that the interaction between RCQ and heme is predominant through the
      quinoline moiety in a mechanism of action similar to that observed for CQ.

PMID- 21095122
TI  - Bitriazolyl acyclonucleosides synthesized via Huisgen reaction using internal
      alkynes show antiviral activity against tobacco mosaic virus.
AB  - A family of novel bitriazolyl acyclonucleosides were synthesized using a simple
      and convenient one-step synthetic procedure via the Huisgen reaction by addition
      of NaN(3) onto triazole nucleosides bearing internal alkynyl groups introduced at
      the 5-position of the triazole ring. Some of the compounds exhibited interesting
      antiviral activity against tobacco mosaic virus, demonstrating the importance of
      the bitriazolyl motif for the observed antiviral activity.

PMID- 21095123
TI  - Novel gratisin derivatives with high antimicrobial activity and low hemolytic
      activity.
AB  - The substitution of each constituent amino acid residue of gratisin (GR) with Ala
      residue indicated that each side chain structure of the constituent amino acid
      residues affect largely the antibiotic and hemolytic activities of GR. Among
      them, the substitution of Pro residues at positions 5 and 5' with a cationic
      amino acid residues (Lys and Arg) results the high antibiotic activity and the
      low toxicity against human blood cells. Thus, we have found a novel position on
      the scaffold of GR at Pro(5,5') residues whose modification will significantly
      lower the unwanted hemolytic activity and enhance the desired antibiotic
      activity.

PMID- 21095124
TI  - A new and efficient synthetic route for the anxiolytic agent CL285032.
AB  - CL285032 is an anxiolytic compound currently under investigation as a possible
      treatment for canine noise phobia associated anxiety. A robust scale-up and
      manufacturing process is essential for the development and marketability of the
      drug. The current synthetic route, although reliable, requires seven steps and
      has a low overall yield (18%), leaving opportunity for improvement. We are
      presenting an efficient alternative approach toward the synthesis of CL285032 and
      the results thereof.

PMID- 21095125
TI  - Synthesis and biological activity of novel 5'-arylamino-nucleosides by microwave
      assisted one-pot tandem Staudinger/aza-Wittig/reduction.
AB  - Novel pseudonucleosides with benzylamino group on 5'-position (4) were
      synthesized by using the microwave-assisted one-pot tandem Staudinger/aza
      Wittig/reduction reaction in good yields of 55.2-71.7%. The deacetylation of 4
      afforded compounds 5. HIV-1 reverse transcriptase (RT) inhibitory and antitumor
      activities were preliminarily evaluated with 5. The results showed that the new
      pseudonucleosides (5) could effectively inhibit HIV-1 RT activity, but no
      antitumor activity.

PMID- 21095126
TI  - Discovery of 1-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroquinolin-4
      amine, a dual serotonin and dopamine reuptake inhibitor.
AB  - The present work describes a series of novel tetrahydroquinoline amines that
      potently inhibit the in vitro reuptake of serotonin and dopamine (dual reuptake
      inhibitors). The compounds are structurally related to a series we disclosed
      previously, but are improved with respect to cytochrome P-450 enzyme (CYP) and
      potassium ion channel Kv11.1 (hERG) inhibition and synthetic accessibility. The
      detailed synthesis and in vitro activity and ADME profile of the compounds is
      described, which represent a previously undisclosed dual reuptake inhibitor
      chemotype.

PMID- 21095127
TI  - Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4
      oxadiazoles as antifungal agents.
AB  - Sodium bisulfite has been reported first time for the synthesis of 2,5
      disubstituted 1,3,4-oxadiazole using microwave and conventional method in ethanol
      water. The yields obtained are in the range of 90-95% using microwave and 87-91%
      using conventional method. All the synthesized compounds (8a-8s) are novel and
      were evaluated for their in vitro antifungal activity. SAR for the series has
      been developed by comparing their MIC values with miconazole and fluconazole.
      Some of the compounds from the series like 8k was equipotent with miconazole
      against Candida albicans and Fusarium oxysporum. Also compound 8n was equipotent
      with miconazole against F. oxysporum.

PMID- 21095128
TI  - Squat-to-reach task in older and young adults: kinematic and electromyographic
      analyses.
AB  - The purpose of this study was to compare the two-dimensional kinematic and
      electromyographic (EMG) changes during the squat-to-reach task in older and young
      adults. Twenty-six older adults and thirty-three young adults were studied. A 16
      channel telemetry system was used for recording muscular activity and kinematic
      data during two trials of a squat-to-reach task. Surface EMG data were recorded
      on select muscles of the trunk and the lower extremity on the dominant side. An
      electrogoniometer was fixed over the knee joint, and an inclinometer was fastened
      on the head and thigh to record kinematic data. The task was split into six
      movement phases based on the angular displacement and velocities of the knee
      joint. The mean values of the maximal displacements in the sagittal plane of the
      head, knee, and thigh were significantly (p<0.05) lower, but those in the frontal
      plane of the head and thigh were significantly (p<0.05) higher in older adults
      than in young adults. Thigh muscle activities were significantly (p<0.05) higher
      in older adults than in young adults throughout the movements. The trunk and leg
      muscles contracted earlier, but the hip adductors contracted later in older
      adults compared to young adults (p<0.05). The older adults squatted in a shallow
      and heel-off posture during forward reaching tasks. Therefore, older adults had
      increased lateral flexion of the head to compensate for insufficient knee flexion
      during the squat-to-reach movement and required increased activity of the posture
      muscles to maintain lateral stability.

PMID- 21095129
TI  - Age-related deficits of dual-task walking: the role of foot vision.
AB  - Previous studies found that age-related deficits of dual-task walking emerge with
      secondary tasks that require substantial visual processing, but are absent with
      tasks that require little or no visual processing. We evaluated whether this is
      so because visual tasks typically interfere with foot vision, on which older
      persons depend more heavily than young ones. Young (25+/-3 years) and older (69+/
      5 years) subjects walked along a straight path and checked boxes on a handheld
      panel, separately or concurrently. The panel was either transparent or opaque,
      thus allowing or blocking vision of the feet, respectively. We quantified
      subjects' performance by spatial and temporal gait measures, and as the speed of
      checking. An analysis of variance revealed significant effects of age and of
      condition (single, dual) for several gait measures, as well as for checking
      speed. The dual-task costs (|dual-single|/single) averaged 0.04+/-0.14 in younger
      and 0.33+/-0.30 in older subjects; this age difference was significant in a t
      test (p<0.01). Most importantly, performance measures obtained with the
      transparent and with the opaque panel were not significantly different. In
      conclusion, our study confirms previous findings about age-related deficits of
      walking with a concurrent visual task, documents for the first time that these
      deficits influence the entire spatio-temporal gait structure, but provides no
      support for the notion that they reflect an increased dependence on foot vision.

PMID- 21095130
TI  - Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential
      application for the treatment of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease
      currently without a cure. Mutations in copper/zinc superoxide dismutase 1 (SOD1)
      have been implicated in the pathophysiology of this disease. Using a high
      throughput screening assay expressing mutant G93A SOD1, two bioactive chemical
      hit compounds (1 and 2), identified as arylsulfanyl pyrazolones, were identified.
      The structural optimization of this scaffold led to the generation of a more
      potent analogue (19) with an EC(50) of 170nM. To determine the suitability of
      this class of compounds for further optimization, 1 was subjected to a battery of
      pharmacokinetic assays; most of the properties of 1 were good for a screening
      hit, except it had a relatively rapid clearance and short microsomal half-life
      stability. Compound 2 was found to be blood-brain barrier penetrating with a
      brain/plasma ratio=0.19. The optimization of this class of compounds could
      produce novel therapeutic candidates for ALS patients.

PMID- 21095131
TI  - 3-Arylisoquinolines as novel topoisomerase I inhibitors.
AB  - Topoisomerase I (topo I) is an essential enzyme for vital cellular processes.
      Inhibition of topo I activities is lethal and leads to cell death, thus
      establishing topo I as a promising target for cancer treatment. Camptothecin, a
      natural alkaloid, inhibits topo I. Topotecan and irinotecan, synthetic
      derivatives of camptothecin, are the most potent anticancer drugs in clinical
      use. However, several limitations of camptothecins such as solubility, toxicity,
      stability, resistance and the required high drug dose have encouraged the
      development of non-camptothecin topo I inhibitors. Natural alkaloid
      benzo[c]phenanthridines and synthetic indenoisoquinolines have been extensively
      studied as alternatives to camptothecin. Interestingly, these non-camptothecin
      topo I inhibitors share a common 3-arylisoquinoline scaffold. This review will
      describe the development of novel indeno[1,2-c]isoquinolines, isoindolo[2,1
      b]isoquinolines, 12-oxobenzo[c]phenanthridines and benz[b]oxepines with a 3
      arylisoquinoline nucleus as topo I inhibitors.

PMID- 21095132
TI  - Synovial chondromatosis originally arising in the lower compartment of
      temporomandibular joint: a case report and literature review.
AB  - INTRODUCTION: More than 200 cases of synovial chondromatosis (SC) in the TMJ were
      reported. Most of SC described exclusively involved the upper compartment of the
      joint. SC originally arising in the lower compartment is rarely found. MATERIAL
      AND METHODS: This article presents a 50-year-old man with a slow growing, pain,
      preauricular swelling in left side and the limitation of mouth-opening. Panoramic
      radiograph, CT scans and MR images were taken. An arthroscopic examination and a
      surgical intervention were performed. RESULTS: Panoramic radiograph and CT scans
      didn't reveal the calcifying lesions in left TMJ region. Sagittal MR images and
      the arthroscopic examination demonstrated distinct nodules within an extremely
      expanded lower joint compartment and a normal position of the articular disc. All
      loose bodies and grossly abnormal synovium were removed. The diagnosis of SC was
      confirmed by histologic examination. CONCLUSION: MRI and arthroscopy may be
      helpful diagnostically. Removal of all involved synovium, and loose cartilaginous
      bodies may be required for adequate treatment.

PMID- 21095133
TI  - A rare bilateral Tessier no. 6 and 7 clefts.
AB  - The authors describe a patient with bilateral Tessier no. 6 and no. 7 clefts. The
      case consists of macrostomia combined with maxillary, zygomatico-orbito-temporal
      deformities, dental anomalies and mandibular retrusion. In addition, the cleft is
      located bilaterally in the maxillary arch with a double deciduous posterior
      dentition. This is rare. The clinical and radiological features are reported and
      the treatment plans are discussed.

PMID- 21095134
TI  - Clinical value of intra-operative transit-time flow measurement for coronary
      artery bypass grafting: a prospective angiography-controlled study.
AB  - OBJECTIVE: Transit-time flow measurement (TTFM) is the most widely used method
      for intra-operative graft quality control in coronary artery bypass surgery.
      Although it may provide the opportunity for the surgeon to promptly revise the
      graft before the patient is discharged from the operating room, controlled
      clinical data on the ultimate usefulness of the TTFM are scarce. Clear cut-off
      values for when to revise grafts have not been set. METHODS: A total of 204
      consecutive grafts (left internal mammary artery (n=46), vein graft (n=155), and
      radial artery (n=3)) underwent TTFM in 75 elective coronary artery bypass
      grafting (CABG) patients. The following parameters were recorded: mean graft flow
      (MGF), pulsatility index (PI), and insufficiency ratio (IR). After a mean follow
      up of 199 +/- 42 days, coronary angiography was performed for assessment of graft
      patency. RESULTS: A total of 166 grafts were found to be patent (85%), and 29
      (15%) were completely occluded. The median and interquartile range (IQR) of MGF
      for the occluded grafts at the time of surgery was 38 ml min(-1) (IQR, 2549 ml
      min(-1)) and for the patent grafts 45 ml min(-1) (IQR, 31-71 ml min(-1); p=ns].
      The corresponding PI values were 3.3 (IQR, 2.8-5.0) and 2.2 (IQR, 1.7-3.2;
      p=0.003), and the IR values were 1.6 (IQR, 0.6-6.1) and 0.2 (IQR, 0-2.2; p=0.03).
      By receiver operating characteristic (ROC) analysis, the highest sensitivity
      (72%) and specificity (70%) were associated with a PI value>3.0. However, 49 out
      of 70 such grafts (70%) were found to be patent. Furthermore, 10 out of 16 (63%)
      grafts, that had a combination of low flow (MGF<15 ml min(-1)) and high PI
      (>3.0), were patent at control angiography. CONCLUSIONS: TTFM predicts graft
      failure within the 6 months after CABG. However, specific cut-off recommendations
      for when to revise a graft cannot be set on the basis of TTFM. The cut-off values
      suggested in the literature lead to unnecessary graft revisions in the majority
      of cases, and, on the other hand, many technical defects probably remain
      unnoticed. Better methods to assess the quality of coronary artery bypass grafts
      are needed.

PMID- 21095135
TI  - The effect of carbohydrate ingestion on plasma interleukin-6, hepcidin and iron
      concentrations following prolonged exercise.
AB  - The aim of our study was twofold, firstly to examine the relationship between
      plasma concentrations of IL-6, hepcidin and iron following prolonged exercise and
      secondly, to assess the effect of carbohydrate ingestion on circulating hepcidin
      concentration post-exercise. The study was a randomised double-blind cross-over
      design, with participants consuming either a carbohydrate (CHO) or an
      isovolumetric placebo drink throughout the trial. Nine healthy, trained males
      completed a treadmill run at 60% vVO(2max) for 120 min followed by a 5 km time
      trial. Plasma concentrations of both IL-6 and hepcidin significantly increased
      post-exercise following both trials (p<.05) and returned to baseline by 24 h post
      (p>.05). A positive correlation between hepcidin and IL-6 was demonstrated
      immediately following exercise during PLA while there was a trend for a moderate
      correlation during CHO (PLA trial rho=0.81, p<0.001; CHO trial rho=0.36, p=0.07).
      Plasma iron was unaffected immediately post-exercise but significantly reduced by
      24 h post-exercise compared to baseline. CHO ingestion significantly reduced post
      exercise IL-6 (p<.05) but this had no effect on plasma hepcidin or iron
      concentration. Our data demonstrate CHO supplementation does not alter the rapid
      hepcidin response associated with exercise and does not prevent a subsequent fall
      in plasma iron concentration. This finding adds further support to the theory
      that an exercise-induced, up-regulation of hepcidin activity is a mechanism
      causing iron deficiency in endurance athletes.

PMID- 21095136
TI  - Multi-joint movements with reversal in Parkinson's disease: Kinematics and
      electromyography.
AB  - Subjects with Parkinson's disease (PD) presented difficulties in the performance
      of multi-joint movements. The purpose of the study was to determine whether the
      slowness of such movements was caused by the generation of non-linear
      trajectories and/or by a reduction or a deficit in the modulation of EMG
      activity. Nine healthy subjects and 10 subjects with PD performed multi-joint
      movements involving elbow and shoulder with reversal towards three targets in the
      sagittal plane without any constraint. The movement kinematics were calculated
      using X and Y coordinates of the markers positioned on the joints. EMG signals
      were recorded for the muscles related to these movements. The results revealed
      that subjects with PD presented a lower linear speed and the differences between
      them and healthy subjects increased with target distance. The trajectory was
      found to be linear and both groups of subjects had few errors in the targets
      despite the slower muscle activity in subjects with PD. Another interesting
      finding was the EMG pattern of subjects with PD. They showed a difficulty in
      modulating the activity of agonists and antagonists during the different movement
      phases. The low speed movements of PD subjects were attributable to the low EMG
      activity and difficulty in modulating the bursts of muscle activity.

PMID- 21095137
TI  - Radiation exposure after heart transplantation: trends and significance.
AB  - BACKGROUND: Heart transplant recipients are frequently exposed to ionizing
      radiation from various imaging and cardiac procedures. However, radiation
      exposure carries various risks, including cancer. In this retrospective study, we
      calculated the mean cumulative radiation exposure during a 10-year period and the
      subsequent cancer risk after heart transplantation. METHODS: The study included
      all patients who underwent heart transplantation from August 1998 to July 2008 at
      our center. We identified all plain X-ray images, computed tomography, nuclear
      medicine procedures, and cardiac procedures (endomyocardial biopsies, right and
      left heart catheterization, and coronary angiograms) each patient underwent
      during the follow-up period. Radiation doses from cardiac procedures were the
      recorded exposures, and we used reference values for plain X-ray imaging and
      nuclear medicine procedures. RESULTS: The mean radiation dose was 84 mSv during
      the 10-year period, and cardiac procedures represented the largest radiation dose
      at 43.6 mSv (52%). The 10-year cumulative dose represented an additional 1 in 290
      new cancers in the healthy population. Encouragingly, there was a decreasing
      trend of radiation exposure during the study period, with a mean decrease of 4.3
      mSv per year. CONCLUSION: Heart transplant patients are exposed to a 3.5 times
      greater dose of radiation per year compared with radiation from medical imaging
      in general population. The lifetime increase in cancer risk estimated from
      population studies was small. Although, there was a decreasing trend of radiation
      exposure during the study period, further reductions in radiation doses may be
      possible by the use of alternative imaging and non-imaging investigations.

PMID- 21095138
TI  - Implications for families of advances in understanding the genetic basis of
      epilepsy.
AB  - Investigations into families with a large number of individuals with epilepsy
      have led to the discovery of epilepsy-causing (or epilepsy associated) gene
      mutations. These discoveries offer advantages and insights for the patient,
      family, healthcare professionals and biomedical scientists. Despite these
      benefits, there is little evidence about the impact of participation in genetic
      research for families with epilepsy. Here we report on the reflections of
      individuals who have participated in epilepsy genetic research through the Wales
      Epilepsy Research Network (WERN). Undergoing genetic investigation for inherited
      epilepsy has extensive emotive impact, both positive and negative, on individuals
      and families. Recognising these impacts is imperative to researchers working with
      families; having implications for study design, research consent and the
      provision of appropriate support.

PMID- 21095139
TI  - Advances in understanding basic mechanisms of epilepsy and seizures.
AB  - Sixty years ago the clinical neurophysiology of epilepsy had progressed to the
      stage that it posed questions that could be addressed by major advances in
      cellular electrophysiology made around the that time. However, it took about 25
      30 years to build up serious momentum in understanding the mechanisms of
      epileptic discharges. Over the past 2-3 decades developments in pharmacology and
      molecular biology have substantially increased the depth and complexity of our
      insights into the nervous system in general and the epileptic brain in
      particular. One of the biggest advances in our understanding of the brain is in
      its plasticity in the adult - that is its ability to modify its structure and
      function. The current state of play is that for most chronic epileptic foci it is
      possible to identify multiple differences from normal brain tissue in both the
      structure and function of neurons, neuronal networks and glia. This review will
      chart some of this progress to give an idea of the pace of advances over the
      decades.

PMID- 21095140
TI  - Altered mRNA expression due to acute mesenteric ischaemia in a porcine model.
AB  - INTRODUCTION: Messenger RNA (mRNA) changes in the small intestine in response to
      acute mesenteric ischaemia (AMI) could offer novel diagnostic possibilities, but
      have not been described. The aim was to characterize the mRNA response to
      experimental AMI. MATERIALS AND METHODS: Twelve pigs underwent catheterisation of
      the superior mesenteric artery with injection of polivinylalcohol embolisation
      particles or sodium chloride. Laparotomy and intestinal tissue sampling were
      performed. Microarray analysis was performed using the GeneChip((r)) whole
      porcine genome array. RESULTS: Seven down-regulated cellular pathways were
      associated with protein, lipid and carbohydrate metabolism. Seventeen up
      regulated pathways were associated with inflammatory and immunological activity,
      regulation of extracellular matrix and decreased cellular proliferation.
      Thrombospondin (THS), monocyte chemoattractant protein 1(MCP-1) and gap junction
      alpha 1(GJA-1) were consistently up-regulated in all embolised pigs. Genes
      encoding earlier proposed biomarkers for AMI were up-regulated, such as lactate
      dehydrogenase and creatine kinase, or down-regulated, such as intestinal fatty
      acid binding protein and glutathione S-transferase. CONCLUSION: This study
      describes the intestinal tissue response on a gene expression level to AMI. THS,
      MCP-1 and GJA-1 were consistently up-regulated by ischaemia, whereas earlier
      proposed biomarkers for AMI were not. Gene expression may not be directly linked
      to the use of the corresponding proteins as potential clinical biomarkers.

PMID- 21095141
TI  - Prospective comparative analysis of colour-Doppler ultrasound, contrast-enhanced
      ultrasound, computed tomography and magnetic resonance in detecting endoleak
      after endovascular abdominal aortic aneurysm repair.
AB  - OBJECTIVES: To assess the accuracy of colour-Doppler ultrasound (CDUS), contrast
      enhanced ultrasonography (CEUS), computed tomography angiography (CTA) and
      magnetic resonance angiography (MRA) in detecting endoleaks after endovascular
      abdominal aortic aneurysm repair (EVAR). DESIGN: Prospective, observational
      study. MATERIALS AND METHODS: From December 2007 to April 2009, 108 consecutive
      patients who underwent EVAR were evaluated with CDUS, CEUS, CTA and MRA as well
      as angiography, if further treatment was necessary. Sensitivity, specificity,
      accuracy and negative predictive value of ultrasound examinations were compared
      with CTA and MRA as the reference standards, or with angiography when available.
      RESULTS: Twenty-four endoleaks (22%, type II: 22 cases, type III: two cases) were
      documented. Sensitivity and specificity of CDUS, CEUS, CTA, and MRA were 58% and
      93%, 96% and 100%, 83% and 100% and 96% and 100% respectively. CEUS allowed
      better classification of endoleaks in 10, two and one patients compared with
      CDUS, CTA and MRA, respectively. CONCLUSIONS: The accuracy of CEUS in detecting
      endoleaks after EVAR is markedly better than CDUS and is similar to CTA and MRA.
      CEUS seems to be a feasible tool in the long-term surveillance after EVAR, and it
      may better classify endoleaks missed by other imaging techniques.

PMID- 21095142
TI  - Percutaneous access for endovascular aortic aneurysm repair. Potential predictors
      of success must be reappraised.

PMID- 21095143
TI  - In situ revascularisation with silver-coated polyester prostheses and arterial
      homografts in patients with aortic graft infection--a prospective, comparative,
      single-centre study.
AB  - OBJECTIVE: The aim of our study was to evaluate the effectiveness of in situ
      revascularisation with the use of arterial homografts and silver-coated
      prostheses in the treatment of aortic graft infection. MATERIALS: A total of 77
      consecutive patients (74 males, three females, mean age: 58 years), hospitalised
      between 2001 and 2008, were enrolled into the study. Patients were assigned to
      three groups: group 1 (n = 24)--fresh arterial homograft with subsequent
      immunosuppression, group 2 (n = 26)--fresh arterial homograft without
      immunosuppression and group 3 (n = 27)--silver-coated prosthesis. METHODS: The
      course of infection was assessed by scintigraphy with (99m)Technetium-labelled
      leucocytes, Duplex-Doppler ultrasound, angio-computed tomography (CT) and
      microbiological examination. RESULTS: The mean follow-up was 22.8 (+/-10.1)
      months. There was a significant decrease in leucocyte accumulation around the
      graft among all groups (group 1: p = 0.012, group 2: p = 0.006 and group 3: p =
      0.021). The postoperative mortality rate in groups 1,2 and 3 was 8%, 23% and 11%,
      respectively. The postoperative morbidity was 35% in group 2, 16% in group 1 and
      7% in group 3. CONCLUSION: Our study suggests that silver-coated prostheses can
      be as effective as arterial allografts in the treatment of infections of vascular
      prostheses.

PMID- 21095144
TI  - Use and utility of ankle brachial index in patients with diabetes.
AB  - Ankle brachial index (ABI) is a simple method to screen peripheral arterial
      disease (PAD) and to evaluate cardiovascular (CV) prognosis in the general
      population. Measuring it requires a hand-held Doppler probe but it can be done
      also with an automatic device. ABI is an effective tool for clinical practice or
      clinical studies. However, in diabetic patients, it has some specific caveats.
      Sensitivity of the standard threshold of 0.9 appears to be lower in diabetic
      patients with complications. Moreover, highly frequent arterial medial
      calcifications in diabetes increase ABI. It has been demonstrated that
      measurements >1.3 are well correlated with both an increased prevalence of PAD
      and CV risk. Therefore, ABI thresholds of less than 0.9 and more than 1.3 are
      highly suspicious for PAD and high CV risk in diabetic patients. However, when
      there is concomitant clinical peripheral neuropathy or high risk of arterial
      calcification, the efficiency of ABI seems to be limited. In this case, other
      methods should be applied, toe pressure, in particular. Thus, the ABI could be
      used in patients with diabetes, but values should be interpreted with precision,
      according to the clinical situation.

PMID- 21095145
TI  - Comments regarding "Capturing the Essence of Developing Endovascular Expertise
      for the Construction of a Global Assessment Instrument". Eur J Vasc Endovasc Surg
      (2010) 40, 292-302.

PMID- 21095146
TI  - Low usage rate of banked sibling cord blood units in hematopoietic stem cell
      transplantation for children with hematological malignancies: implications for
      directed cord blood banking policies.
AB  - Directed sibling cord blood banking is indicated in women delivering healthy
      babies who already have a sibling with a disease that is potentially treatable
      with an allogeneic cord blood transplant. We evaluated the effectiveness of a
      national directed cord blood banking program in sibling HLA-identical stem cell
      transplantation for hematological malignancies and the factors influencing the
      usage rate of the stored cord blood units. Fifty families were enrolled from
      which, 48 cord blood units were successfully collected and 2 collections failed
      due to damaged cord/placenta at delivery. Among enrolled families 4 children
      needed transplantation; however, only one was successfully transplanted using the
      collected cord blood unit containing 2*10(7) nucleated cells/kg in conjunction
      with a small volume of bone marrow from the same HLA-identical donor. Two
      children received grafts from matched unrelated donors because their sibling cord
      blood was HLA-haploidentical, while the fourth one received bone marrow from his
      HLA-identical brother, since cord blood could not be collected due to damaged
      cord/placenta at delivery. With a median follow-up of 6 years (range, 2-12) for
      the 9 remaining HLA-matched cord blood units, none from the prospective
      recipients needed transplantation. The low utilization rate of sibling cord blood
      in the setting of hematopoietic stem cell transplantation for pediatric
      hematological malignant diseases necessitates the development of directed cord
      blood banking programs that limit long-term storage for banked cord blood units
      with low probability of usage such as non-HLA-identical or identical to patients
      who are in long-term complete remission.

PMID- 21095147
TI  - Effect of anaesthesia on contrast-enhanced ultrasound of the feline spleen.
AB  - The spleens of 18 healthy cats were imaged using contrast-enhanced ultrasound
      (CEUS) to evaluate splenic perfusion and to compare perfusion patterns in awake
      and anaesthetised cats. Two groups of cats were imaged; the first (Group 1)
      consisted of 10 young, anaesthetised cats and the second (Group 2) comprised
      eight young to middle aged cats that were initially imaged when awake and later
      following anaesthesia. A two-phase enhancement of the spleen was observed both in
      awake and in anaesthetised cats. The time to first appearance of the contrast was
      significantly faster in awake (3.9+/-0.6s) than anaesthetised (4.8+/-1.0s) cats
      in Group 2 (P=0.031). A marked heterogeneous perfusion pattern was more prevalent
      in the anaesthetised (50%) compared to the awake (12.5%) animals in Group 2. The
      spleen was heterogeneous for approximately 30s in all groups. The results
      indicated that CEUS suspected focal perfusion defects of the spleen, especially
      during general anaesthesia, should be evaluated with caution and only after the
      initial heterogeneity has disappeared.

PMID- 21095148
TI  - Repetitive transcranial magnetic stimulation (rTMS) as a tool for the treatment
      of chronic visceral pain.

PMID- 21095149
TI  - Consistency of bone turnover marker and calcium responses to parathyroid hormone
      (1-84) therapy in postmenopausal osteoporosis.
AB  - We investigated whether those who experience the greatest increases in bone
      turnover in response to parathyroid hormone (PTH) therapy are the same as those
      who experience elevations in calcium levels. Baseline and follow-up procollagen
      type I N propeptide (PINP), bone-specific alkaline phosphatase (BAP), C-terminal
      telopeptide (CTX), and serum and urinary calcium levels were analyzed post hoc
      from the 119 postmenopausal women with osteoporosis randomized to PTH(1-84) in
      the Parathyroid Hormone and Alendronate trial. Short-term changes in the markers
      of bone turnover were highly correlated with one another (r=0.57-0.87, p<0.001).
      In contrast, change in serum calcium correlated only modestly with changes in
      markers of formation (r=0.22-0.30, p<=0.02) and did not correlate significantly
      with change in CTX (r=0.13, p=0.18). Participants who experienced hypercalcemia
      experienced greater 3-mo changes in BAP than those who did not (78% vs. 42%
      increase in BAP, p=0.04), with similar trends for PINP and CTX. In conclusion,
      the use of 1 marker of bone turnover, rather than multiple markers, may be
      sufficient to assess biochemical response to PTH(1-84). The relationship between
      bone turnover marker and calcium responses to PTH(1-84) is modest and does not
      suggest a profound, broadly heightened responsiveness of certain individuals to
      therapy.

PMID- 21095150
TI  - Bone ultrasound velocity in neonates with intrauterine growth deficit reflects a
      growth continuum.
AB  - Both bone mass by densitometry and speed of sound (SOS) from quantitative
      ultrasound of the bone (QUS) are directly related to bone strength. However,
      reports of lower bone mass but higher SOS in neonates with intrauterine growth
      deficit lead to apparent contradictory conclusions on bone strength. Three groups
      of infants were studied: small for gestation (SGA) with birth weights <=10th
      percentile for gestation and 2 control groups with appropriate birth weights
      (11th to 90th percentile) for gestation (AGA): matched to SGA group for gestation
      and birth weight, respectively. SOS was measured with a commercial QUS instrument
      (Sunlight Omnisense 7000, Sunlight Medical Ltd, Tel Aviv, Israel) and 2
      manufacturer supplied ultrasound probes (CS and CR) for small bones. The SGA
      group had significantly (p<0.01) higher SOS compared with weight matched but
      gestational less matured control group by an average of 54m/s with the CS probe
      and 80m/s with the CR probe but not significantly different from gestation
      matched AGA group. SOS values from both probes were significantly correlated
      (r=0.71-0.91) but were significantly different between probes. Probe failure
      occurred with both probes. We conclude that QUS SOS values in SGA neonates are a
      reflection of a continuum of intrauterine maturation of the skeleton.

PMID- 21095151
TI  - Modification of aspartoacylase for potential use in enzyme replacement therapy
      for the treatment of Canavan disease.
AB  - Canavan disease is a fatal neurological disease without any effective treatments
      to slow the relentless progress of this disorder. Enzyme replacement therapy has
      been used effectively to treat a number of metabolic disorders, but the presence
      of the blood-brain-barrier presents an additional challenge in the treatment of
      neurological disorders. Studies have begun with the aim of establishing a
      treatment protocol that can effectively replace the defective enzyme in Canavan
      disease patients. The human enzyme, aspartoacylase, has been cloned, expressed
      and purified, and the surface lysyl groups modified through PEGylation. Fully
      active modified enzymes were administered to mice that are defective in this
      enzyme and that show many of the symptoms of Canavan disease. Statistically
      significant increases in brain enzyme activity levels have been achieved in this
      animal model, as well as decreases in the elevated substrate levels that mimic
      those found in Canavan disease patients. These results demonstrate that the
      modified enzyme is gaining access to the brain and functions to correct this
      metabolic defect. The stage is now set for a long term study to optimize this
      enzyme replacement approach for the development of a treatment protocol.

PMID- 21095152
TI  - The obesity paradox in community-acquired bacterial pneumonia.
AB  - BACKGROUND: The impact of obesity on the outcome of pneumonia is uncertain.
      METHODS: We retrospectively identified 266 hospitalized patients with proven
      pneumococcal or Haemophilus community-acquired pneumonia who had at least one
      body mass index (BMI, kg/m2) value documented in the 3 months before admission.
      Patients were classified as underweight (BMI <18.5), normal weight (BMI 18.5 to
      <25), overweight (BMI 25 to <30), or obese (BMI >=30). The association of
      absolute BMI values and BMI categories with the mortality at 30 days after
      admission for pneumonia was investigated. RESULTS: Increasing BMI values were
      associated with reduced 30-day mortality, even after adjustment for significant
      covariates (odds ratio 0.88, confidence interval 0.81-0.96; p<0.01). There was a
      significant trend towards lower mortality in the overweight and obese (non
      parametric trend, p=0.02). CONCLUSIONS: Our data suggest that obesity may exert a
      protective effect against 30-day mortality from community-acquired bacterial
      pneumonia.

PMID- 21095153
TI  - Experimental study of the mechanical properties of human abdominal fascia.
AB  - The aim of the study is to characterise mechanical properties of human abdominal
      fascia according to its direction of loading and localization. The one
      dimensional tensile behaviour of human abdominal fascia and its orthotropy has
      been studied experimentally using human umbilical (UF) and transversalis fascia
      (FT). The specimens have been cut and stretched parallel and orthogonal to the
      main fibre bundles. 90 specimens 10 mm wide and up to 70 mm long have been
      tested. The following mechanical parameters, characterising tensile properties of
      human abdominal fascia, have been calculated from the obtained stress-stretch
      ratio curves: maximal stress T(L)(max), stretch ratio at maximal stress
      lambda(T(max)), maximal stretch ratio at failure lambda(max), and a secant
      modulus E(i). The tissue strips obtained from defined areas reveal break stress
      between 0.63 and 1.99 MPa for FT and 0.93-1.61 MPa for UF. The parameter
      estimation has shown that in the physiological strain range specimens from both
      type of fascia can be considered orthotropic material according to their secant
      module, maximum stress T(L)(max) and stretch at maximum stress. Anisotropy factor
      AF (ratio of the stress in longitudinal and transverse directions) has been used
      to establish the level of the orthotropy of material and its variations with the
      stretch ratio. The maximum AF is 4.3 for FT at 20% deformation and 3.3 for UF at
      5% deformation. The differences between the mechanical properties of FT and UF
      according to localization are not statistically significant thus the mechanical
      properties of human abdominal fascia are not affected by the localization.

PMID- 21095154
TI  - The role of Th17 cytokines in primary mucosal immunity.
AB  - The T helper type 17 (Th17) lineage of CD4+ T-cells produce several effector
      molecules including IL-17A, IL-17F, IL-21, and IL-22. In addition to CD4+,
      alphabeta T-cells, these cytokines can be produced by natural killer and
      gammadelta T-cells. These effector cytokines can be produced rapidly upon
      infection at mucosal sites and evidence to date strongly implicates that this arm
      of the immune system plays a critical role in mucosal immunity to many
      extracellular pathogens. Moreover these cytokines can also coordinate adaptive
      immunity to some intracellular pathogens. In this review, we will highlight
      recent progress in our understanding of these cytokines, and mechanisms of their
      effector function in the mucosa.

PMID- 21095155
TI  - Little evidence for fire-adapted plant traits in Mediterranean climate regions.
AB  - As climate change increases vegetation combustibility, humans are impacted by
      wildfires through loss of lives and property, leading to an increased emphasis on
      prescribed burning practices to reduce hazards. A key and pervading concept
      accepted by most environmental managers is that combustible ecosystems have
      traditionally burnt because plants are fire adapted. In this opinion article, we
      explore the concept of plant traits adapted to fire in Mediterranean climates. In
      the light of major threats to biodiversity conservation, we recommend caution in
      deliberately increasing fire frequencies if ecosystem degradation and plant
      extinctions are to be averted as a result of the practice.

PMID- 21095157
TI  - Statistical optimization of culture conditions for the production of enniatins H,
      I, and MK1688 by Fusarium oxysporum KFCC 11363P.
AB  - The aim of this study was to optimize the culture conditions for the production
      of biological cyclic hexadepsipeptides (enniatins H, I and MK1688) from Fusarium
      oxysporum KFCC 11363P. Tests of 10 complete or chemically defined liquid culture
      media revealed that Fusarium defined medium was the best for the production of
      enniatins (produced amounts: enniatin H, 185.4 mg/L; enniatin I, 349.1mg/L;
      enniatin MK1688, 541.1mg/L; and total enniatins, 1075.6 mg/L). On the eighth day
      after inoculation, the maximal production of enniatins was observed at 25 degrees
      C in Fusarium defined medium. The optimal carbon and nitrogen sources for
      producing biological cyclic hexadepsipeptides (enniatins H, I, and MK1688) were
      sucrose and NaNO(3), respectively, and their optimal concentrations were
      determined by the principle of response surface methodology. It was confirmed
      that using the optimized growth medium compositions increased the amounts of
      enniatins H, I, and MK1688, and total enniatins produced to 695.2, 882.4, 824.8,
      and 2398.5mg/L, respectively. These findings will assist in formulating
      microbiological media useful for enniatin research.

PMID- 21095156
TI  - Genome mining for ribosomally synthesized natural products.
AB  - In recent years, the number of known peptide natural products that are
      synthesized via the ribosomal pathway has rapidly grown. Taking advantage of
      sequence homology among genes encoding precursor peptides or biosynthetic
      proteins, in silico mining of genomes combined with molecular biology approaches
      has guided the discovery of a large number of new ribosomal natural products,
      including lantipeptides, cyanobactins, linear thiazole/oxazole-containing
      peptides, microviridins, lasso peptides, amatoxins, cyclotides, and conopeptides.
      In this review, we describe the strategies used for the identification of these
      ribosomally synthesized and posttranslationally modified peptides (RiPPs) and the
      structures of newly identified compounds. The increasing number of chemical
      entities and their remarkable structural and functional diversity may lead to
      novel pharmaceutical applications.

PMID- 21095158
TI  - Multigenerational mitochondrial alterations in pneumocytes exposed to oil fly ash
      metals.
AB  - Oil fly ash (OFA), containing high amounts of transition metals, is among the
      most reactive airborne particulate matter emissions, which have been associated
      with several diseases, such as chronic obstructive pulmonary diseases (COPD),
      lung cancer, and cardiovascular diseases. The aim of the present study was to
      evaluate mitochondrial alterations in OFA-exposed cultured pneumocytes and in
      their progeny. Alveolar epithelial cells (A549 line) were exposed either to an
      OFA water solution, containing 68.8 MUM vanadium (V), 110.4 MUM iron (Fe), and
      18.0 MUM nickel (Ni), or to the individual metal solutions. Structural and
      functional mitochondrial parameters were determined in exposed cultures and in 3
      consecutive subcultures. OFA, V and Fe solutions caused a time-dependent loss of
      mitochondrial enzymatic activity, glutathione depletion, generation of lipid
      hydroperoxides, hydrogen peroxide and other reactive oxygen species, especially
      in G(0)-G(1) phase cells, accompanied by a decrease in mitochondrial mass and
      transmembrane potential. Mitochondrial alterations were partly transmissible to
      daughter cells for up to 3 generations. Fe and especially V were responsible for
      the observed mitochondrial alterations in pneumocytes exposed to OFA. Spread of
      mitochondrial dysfunctions to daughter cells is expected to amplify oxidative
      stress in the respiratory epithelium and to play an important role in the
      pathogenesis of respiratory diseases.

PMID- 21095160
TI  - Which interventions are used by health care professionals to enhance medication
      adherence in cardiovascular patients? A survey of current clinical practice.
AB  - BACKGROUND: Complex medication regimens are often required to manage
      cardiovascular diseases. As non-adherence, which can have severe negative
      outcomes, is common among cardiovascular patients, various interventions to
      improve adherence should be implemented in daily practice. AIM: To assess which
      strategies cardiovascular nurses and allied health professionals utilize to (1)
      assess patients' adherence to medication regimen, and (2) enhance medication
      adherence via educational/cognitive, counseling/behavioral, and
      psychological/affective interventions. METHOD: A 45-item questionnaire to assess
      adherence assessment and interventional strategies utilized by health care
      professionals in daily clinical practice was distributed to a convenience sample
      of attendants of the 10th Annual Spring Meeting of the European Society of
      Cardiology Council on Cardiovascular Nursing and Allied Professions conference in
      Geneva (Switzerland) in March 2010. Respondents not in direct clinical practice
      were excluded. Descriptive statistics were used to describe practice patterns
      regarding adherence management. RESULTS: Of 276 distributed questionnaires, 171
      (62%) were returned, of which 34 (20%) were excluded as respondents performed no
      direct patient care. Questioning patients about non-adherence during follow-up
      was the most frequently reported assessment strategy (56%). Educational/cognitive
      adherence enhancing interventions were used most frequently, followed by
      counseling/behavioral interventions. Psychological/affective interventions were
      less frequently used. The most frequent intervention used was providing reading
      materials (66%) followed by training patients regarding medication taking during
      inpatient recovery (48%). Slightly over two-thirds (69%) reported using a
      combination of interventions to improve patient's adherence. CONCLUSION:
      Educational interventions are used most in clinical practice, although evidence
      shows they are less effective than behavioral interventions at enhancing
      medication adherence.

PMID- 21095159
TI  - Tai Chi as an adjunct physical activity for adults aged 45 years and older
      enrolled in phase III cardiac rehabilitation.
AB  - BACKGROUND: Cardiac rehabilitation improves physical, cognitive and psychosocial
      functioning, yet services are greatly underutilized with increasing patterns of
      attrition over time. Tai Chi has been suggested as a possible adjunct to cardiac
      rehabilitation exercise training. AIM: To describe differences in physical,
      cognitive and psychosocial functioning among adults >= 45 years old attending
      phase III cardiac rehabilitation, who have or have not self-selected Tai Chi
      exercise as an adjunct physical activity. METHODS: A cross-sectional design
      compared subjects attending group-based Wu style Tai Chi classes plus cardiac
      rehabilitation, with cardiac rehabilitation only. Subjects had a battery of
      physical and cognitive functioning tests administered to examine aerobic
      endurance, balance, strength, and flexibility, verbal retrieval/recall,
      attention, concentration and tracking. Subjects completed a health survey to
      ascertain cardiac event information, medical history, and psychosocial
      functioning (i.e. health-related quality of life, stress, depressive symptoms,
      social support, and Tai Chi self-efficacy). RESULTS: A total of 51 subjects (75%
      married, 84% college-educated, 96% White/European-American) participated.
      Subjects were on average 70 (+/- 8) years old and had attended cardiac
      rehabilitation for 45 (+/- 37) months. Approximately 45% (n = 23) attended Tai
      Chi classes plus cardiac rehabilitation, while 55% (n = 28) attended cardiac
      rehabilitation only. Subjects attending Tai Chi plus cardiac rehabilitation had
      better balance, perceived physical health, and Tai Chi self-efficacy compared to
      those attending cardiac rehabilitation only (p <= 0.03). CONCLUSION: Tai Chi can
      be easily implemented in any community/cardiac rehabilitation facility, and may
      offer adults additional options after a cardiac event.

PMID- 21095161
TI  - Commentary to 'A retrospective observational study of enuresis, daytime voiding
      symptoms, and response to medical therapy in children with attention deficit
      hyperactivity disorder and autism spectrum disorder'.

PMID- 21095163
TI  - Trachelectomy for cancer of the cervix: dargent's operation. Vaginal hysterectomy
      for early cancer of the cervix stage IA1 and CIN III.
AB  - Radical vaginal trachelectomy is today an established method of treating selected
      women with cervical cancer stage IA2 and IB1, with tumour size less than 2cm
      without precluding future childbearing. This technique has been used for more
      than 20 years with reassuring oncological safety and excellent obstetrical
      outcomes. The procedure is a combination of laparoscopy for pelvic
      lymphadenectomy and challenging classic vaginal surgery to resect the tumour,
      part of the parametrium and upper vagina. Complications are in the range of 8
      13%. Recurrence and death occur in 5 and 3%, respectively, as good as figures for
      radical hysterectomy. Rate of second trimester miscarriage is 8-10%, and that of
      preterm delivery 20-30%. More than 900 cases with 200 children are now reported
      in the published literature.

PMID- 21095164
TI  - A case of late epidural hematoma in a patient on clopidogrel therapy
      postoperatively: when is it safe to resume antiplatelet agents?
AB  - BACKGROUND CONTEXT: The use of antiplatelet agents after coronary artery stent
      placement is currently recommended to prevent coronary stent obstruction. These
      patients may have concurrent disabling spinal stenosis and require spinal
      decompression. Resuming antiplatelet agents as soon as possible after spinal
      surgery is recommended. PURPOSE: To describe a unique case of late postoperative
      epidural hematoma occurring with the use of clopidogrel. STUDY DESIGN: A case
      report and review of the literature. METHODS: The hospital chart, history,
      physical examination, and imaging of a single patient were reviewed. RESULTS: A
      59-year-old man underwent spinal decompression and fusion for neurogenic
      claudication with lumbar spinal stenosis and spondylolisthesis while managed on
      clopidogrel for prevention of thrombosis after cardiac stent placement. He
      developed a symptomatic epidural hematoma 12 days postoperatively, well outside
      the usual time frame for this complication. The patient was closely monitored,
      and lumbar radiculopathy resolved over the ensuing days. CONCLUSION: After spinal
      surgery and resumption of antiplatelet therapy, the physician needs to maintain
      vigilance in observing patients for late postoperative complications such as
      epidural hematoma, which could have catastrophic consequences if not recognized
      in a timely manner.

PMID- 21095166
TI  - The management of portal hypertensive gastropathy and gastric antral vascular
      ectasia.
AB  - Portal hypertensive gastropathy and gastric antral vascular ectasia are gastric
      mucosal lesions that can cause chronic gastrointestinal haemorrhage and,
      consequently, chronic anaemia, in patients with cirrhosis. Although chronic
      anaemia is the most common clinical manifestation, these entities may also lead
      to acute gastrointestinal bleeding. Despite similar clinical manifestations,
      their pathophysiology and management are entirely different. Their diagnosis is
      endoscopic and although generally each of them has a characteristic endoscopic
      appearance and distribution, there are cases in which the differential is
      difficult and must rely on histology. This review focuses on the management of
      both entities. The mainstay of management of portal hypertensive gastropathy is
      based on portal-hypotensive pharmacological treatment whilst gastric antral
      vascular ectasia benefits from endoscopic therapy. More invasive options should
      be reserved for refractory cases.

PMID- 21095165
TI  - Determination of beta-lactam antibiotics in milk based on magnetic molecularly
      imprinted polymer extraction coupled with liquid chromatography-tandem mass
      spectrometry.
AB  - In this work, a rapid and selective method was successfully developed using the
      magnetic molecularly imprinted polymer (MMIP) as sorbent for the extraction of
      beta-lactam antibiotics (BLAs) from milk samples. The MMIP has been prepared
      using penicillin V potassium (PENV) as template molecule, methacrylic acid as
      functional monomer, ethylene glycol dimethacrylate as crosslinking agent and
      Fe(3)O(4) magnetite as magnetic component. The experimental results showed that
      the MMIP had high affinity and selectivity toward PENV and other structurally
      related BLAs. The extraction process was carried out in a single step by mixing
      the extraction solvent, MMIPs and milk samples under ultrasonic action. When the
      extraction was completed, the MMIPs adsorbing the analytes were separated from
      the sample matrix by an external magnet. The analytes eluted from the MMIP were
      analyzed by liquid chromatography-tandem mass spectrometry. For achieving optimal
      preconcentration and reducing non-specific interactions, various parameters
      affecting the extraction efficiency such as extraction mode, extraction solvent,
      the amount of MMIPs, extraction time, washing solution and eluting solution were
      comprehensively evaluated. Under the optimal conditions, the detection limits of
      BLAs are in the range of 1.6-2.8 ng mL(-1). The relative standard deviations of
      intra- and inter-day ranging from 3.2% to 8.3% and from 3.6% to 9.8% are
      obtained, respectively. The method was applied to determine BLAs including PENV,
      amoxicillin and oxacillin in five milk samples from different provenances. The
      recoveries of BLAs in these samples from 71.6% to 90.7% are obtained.

PMID- 21095162
TI  - Anti-tumor potential of type-I NKT cells against CD1d-positive and CD1d-negative
      tumors in humans.
AB  - Valpha24-invariant natural killer T cells (NKTs) are strictly CD1d-restricted,
      and CD1d expression has been found in several types of leukemia and lymphoma as
      well as in brain tumors suggesting that these malignancies could be targeted for
      direct NKT-cell cytotoxicity. Several studies have revealed strong positive
      associations between the numbers of tumor-infiltrating or circulating NKTs with
      improved disease outcome in patients with diverse types of CD1d-negative solid
      tumors. The mechanism by which NKTs mediate anti-tumor activity against CD1d
      negative tumors has long remained enigmatic. Recent evidence indicates that NKTs
      can suppress tumor growth indirectly by targeting CD1d-positive elements of tumor
      supportive stroma such as tumor-associated macrophages. This review summarizes
      the current knowledge about the mechanisms that regulate NKT-cell localization to
      the tumor site and their interaction with the tumor microenvironment. The
      discussed strategies for pharmacologic modulation and genetic engineering of NKTs
      may lead to development of effective and broadly applicable immunotherapies of
      cancer.

PMID- 21095167
TI  - Psychometric properties of the Revised Male Body Attitudes Scale among Irish men.
AB  - The psychometric properties of a revised version of the Male Body Attitudes Scale
      (Tylka, Bergeron, & Schwartz, 2005) were investigated using two independent
      online samples of Irish men (ns=241 and 253, respectively). Exploratory factor
      analyses suggested that a 15-item, 3-factor solution representing men's attitudes
      toward their body fat, muscularity, and height best described the data. The
      internal consistency and construct validity of scores on the Revised Male Body
      Attitudes Scale suggest that this measure holds promise as an indicant of men's
      attitudes toward their physical appearance. Limitations and strengths associated
      with the current research are discussed and directions for future research are
      outlined.

PMID- 21095168
TI  - European College of Orthodontics: Commission of Affiliation and Titularisation.
AB  - Date of birth: 21/11/1994; gender: female. A. PRETREATMENT RECORDS: 02/11/2004
      (age of patient: 10years). DIAGNOSIS: Skeletal Class II, hyperdivergent, dental
      Class II, arch-length discrepancy (ALD), anterior open bite, lingual dysfunction.
      TREATMENT: First functional stage: ENT check-up, tongue rehabilitation using
      retroincisal spurs. Second orthodontic stage: multibracket appliance with
      extraction of 15-25-35-45. B. END-OF-TREATMENT RECORDS: 18/09/2007 (age of
      patient: 12y10m). RETENTION: Upper arch: palatal wire bonded from 12 to 22 and
      nightguard. Lower arch: bonded lingual wire from 33 to 43. C. END-OF-TREATMENT
      RECORDS: 20/11/2007 (age of patient: 13years). D. CLINICAL OBSERVATIONS: Poor
      state of teeth: risk of caries.

PMID- 21095170
TI  - European College of Orthodontics: Commission of Affiliation and Titularisation.
AB  - Date of birth: 18/08/1988; gender: female. A. PRETREATMENT RECORDS: 10/2002 (age
      of patient: 11years 9months). DIAGNOSIS: Ariane R., aged 11years 9months,
      presented with: an Angle Class II,1 malocclusion; an arch-length discrepancy
      (ALD) with a 2-mm deviation to the right of the mandibular midline; incisor
      deepbite, Ballard Class II skeletal relations in a hypodivergent facial pattern.
      TREATMENT: Extractions of 14, 24, 34, 44; fixed appliance: 0.022*0.028
      bimaxillary multiband (non-preformed brackets); a transpalatal arch on 16 and 26.
      B. END-OF-TREATMENT RECORDS: 11/2005 (age of patient: 13years 10months).
      RETENTION: Maxillary Hawley plate; lingual bonded wire from 33 to 43. C. END-OF
      TREATMENT RECORDS: 9/2006 (age of patient: 16years 2months).

PMID- 21095172
TI  - Two new protocols to enhance the production and isolation of human induced
      pluripotent stem cell lines.
AB  - There are two critical stages in the retroviral reprogramming of somatic cells to
      produce human induced pluripotent stem cell (hiPSC) lines. One is the production
      of high titer virus required to reprogram somatic cells; the other is
      identification of true hiPSC colonies from heterogeneous cell populations, and
      their isolation and expansion to generate a sustainable, pluripotent stem cell
      line. Here we describe simple, time-saving methods to address the current
      difficulties at these two critical junctures. First, we have developed a method
      to increase the number of infectious viral units 600-fold. Second, we have
      developed a TRA-1-81-based positive selection column method for isolating "true"
      hiPSCs from the heterogeneous cell populations, which overcomes the labor
      intensive and highly subjective method of manual selection of hiPSC colonies. We
      have used these techniques to produce 8 hiPSC lines from human fibroblasts and we
      believe that they are of considerable utility to researchers in the hiPSC field.

PMID- 21095174
TI  - Gaps between evidence-based guidelines and the daily surgical practices.

PMID- 21095173
TI  - The presence of Y chromosomal deoxyribonucleic acid in the female vaginal swab:
      possible implications for human papillomavirus testing.
AB  - BACKGROUND: Vaginal self-sampling for human papillomavirus (HPV) detection is the
      focus of recent research. However, it has been shown previously that male DNA can
      be detected in vaginal swabs. The aim of this study was to investigate whether a
      female vaginal swab may reflect a male active HPV infection. METHODS: Eleven
      women volunteered to take vaginal samples. The first sample was taken within
      hours after unprotected intercourse, the others each following morning for five
      consecutive days. On these samples, a Y-chromosomal locus, as a surrogate marker
      for HPV, was amplified by PCR. To investigate the prevalence of male DNA in self
      obtained vaginal swabs, 282 swabs from 16 women enrolled in an ongoing HPV follow
      up study were tested. RESULTS: All baseline samples from the 11 women were
      positive for male DNA. In the follow-up samples, positivity ranged from day 1
      till day 5, with a sharp drop from day 2 (91%) to day 3 (36%). Of 282 swabs, 23
      (8.2%) were positive for male DNA. However, 10 of these 23 swabs were provided by
      one single woman. DISCUSSION: Since HPV can be deposited by the male in the
      vagina, either through semen, or through exfoliated epithelial cells, our results
      are of some importance when testing for HPV in vaginal swabs. It is conceivable
      that women with acquired immunity to HPV, but with an HPV positive partner, are
      found to be HPV positive in the swab. However, larger studies on more diverse
      populations are warranted.

PMID- 21095175
TI  - Oncoplastic conservative treatment for breast cancer (part 4): techniques for
      inner quadrants.

PMID- 21095176
TI  - Robotic thyroid surgery using a gasless transaxillary approach: cosmetic
      improvement or improved quality of surgical dissection?
AB  - In head and neck surgery, minimally invasive approaches have been typically
      avoided due to concerns about visualization, possible damage to vital structures,
      and limited availability of effective instrumentation. The incorporation of
      robotic technology in surgery is now an accepted fact, and because of the
      complexities of certain laparoscopic procedures, the extended capabilities
      offered by robotic technology have gained wide acceptance. We report the case of
      a patient who underwent a robotic total thyroidectomy using a gasless right
      transaxillary approach. This technique provides a high quality image leading to
      improved visualization of vital structures during thyroidectomy with the added
      advantage of avoidance of a neck incision. Several issues regarding this
      technique remain to be clarified and evaluated in multicenter studies: patient
      selection, surgeon training and learning curve, postoperative morbidity due to
      recurrent nerve and parathyroid injury, long term oncologic and cosmetic results.
      However, we believe that robotic thyroid surgery using a gasless transaxillary
      approach will advance the frontiers of minimally invasive endocrine surgery.

PMID- 21095177
TI  - Oncoplastic conservative treatment for breast cancer (part 3): techniques for the
      upper quadrants.

PMID- 21095178
TI  - Fifteen common mistakes encountered in clinical research.
AB  - The baseline standards for minimally acceptable science are improving as the
      understanding of the scientific method improves. Journals publishing research
      papers are becoming more and more rigorous. For example, in 2001 a group of
      authors evaluated the quality of clinical trials in anesthesia published over a
      20 year period [Pua et al., Anesthesiology 2001;95:1068-73]. The authors divided
      the time into 3 subgroups and analyzed and compared the quality assessment score
      from research papers in each group. The authors reported that the scientific
      quality scores increased significantly in this time, showing more randomization,
      sample size calculation and blinding of studies. Because every journal strives to
      have a high scientific impact factor, research quality is critical to this goal.
      This means novice researchers must study, understand and rigorously avoid the
      common mistakes described in this review. Failure to do so means the hundreds and
      hundreds of hours of effort it takes to conduct and write up a clinical trial
      will be for naught, in that the manuscript with be rejected or worse yet,
      ignored. All scientists have a responsibility to understand research methods,
      conduct the best research they can and publish the honest and unbiased results.

PMID- 21095179
TI  - Influence of Chlorella powder intake during swimming stress in mice.
AB  - We used the forced swimming test to investigate the influence of Chlorella powder
      intake during muscle stress training in mice. After day 14, swimming time was
      about 2-fold longer for Chlorella intake mice than for control swimming mice.
      Microarray analysis revealed that the global gene expression profile of muscle
      from the Chlorella intake mice was similar to that of muscle from the intact (non
      swimming) mice, and the profile of these two groups differed from that of the
      control (swimming) mice. Gene ontology and pathway analyses of gene expression
      data showed that oxidoreductase activity and the leukotriene synthesis pathway
      were repressed in the Chlorella intake mice following the swimming test. In
      addition, measurements of free fatty acids, glucose, triglycerides, and lactic
      acid in the blood of Chlorella intake mice were higher than that of control mice.
      These findings suggest that metabolism in tissues is altered by Chlorella intake.

PMID- 21095180
TI  - The effect of gastric inhibitory polypeptide on intestinal glucose absorption and
      intestinal motility in mice.
AB  - Gastric inhibitory polypeptide (GIP) is released from the small intestine upon
      meal ingestion and increases insulin secretion from pancreatic beta cells.
      Although the GIP receptor is known to be expressed in small intestine, the
      effects of GIP in small intestine are not fully understood. This study was
      designed to clarify the effect of GIP on intestinal glucose absorption and
      intestinal motility. Intestinal glucose absorption in vivo was measured by single
      pass perfusion method. Incorporation of [(14)C]-glucose into everted jejunal
      rings in vitro was used to evaluate the effect of GIP on sodium-glucose co
      transporter (SGLT). Motility of small intestine was measured by intestinal
      transit after oral administration of a non-absorbed marker. Intraperitoneal
      administration of GIP inhibited glucose absorption in wild-type mice in a
      concentration-dependent manner, showing maximum decrease at the dosage of 50
      nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice,
      GIP inhibited glucose absorption as in wild-type mice. In vitro examination of
      [(14)C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent
      glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50
      nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild
      type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor
      antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both
      intestinal transit and glucose absorption in wild-type mice. These results
      demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing
      intestinal motility through a somatostatin-mediated pathway rather than through a
      GLP-1-mediated pathway.

PMID- 21095181
TI  - Clec14a is specifically expressed in endothelial cells and mediates cell to cell
      adhesion.
AB  - Clec14a is a member of the thrombomodulin (TM) family, but its function has not
      yet been determined. Here, we report that Clec14a is a plasma membrane protein of
      endothelial cells (ECs) expressed specifically in the vasculature of mice.
      Deletion mutant analysis revealed that Clec14a mediates cell-cell adhesion
      through its C-type lectin-like domain. Knockdown of Clec14a in ECs suppressed
      cell migratory activity and filopodial protrusion, and delayed formation of tube
      like structures. These findings demonstrate that Clec14a is a novel EC-specific
      protein that appears to play a role in cell-cell adhesion and angiogenesis.

PMID- 21095182
TI  - Cyclic phosphatidic acid influences the expression and regulation of cyclic
      nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 cells.
AB  - Cyclic phosphatidic acid (cPA) is found in cells from slime mold to humans and
      has a largely unknown function. We previously reported that cPA significantly
      inhibited the lipid accumulation in 3T3-L1 adipocytes through inhibition of
      PPARgamma activation. We find here that cPA reduced intracellular triglyceride
      levels and inhibited the phosphodiesterase 3B (PDE3B) expression in 3T3-L1
      adipocytes. PPARgamma activation in adipogenesis that can be blocked by treatment
      with cPA then participates in adipocyte function through inhibition of PDE3B
      expression. We also found the intracellular cAMP levels in 3T3-L1 adipocytes
      increased after exposure to cPA. These findings contribute to the participation
      of cPA on the lipolytic activity in 3T3-L1 adipocytes. Our studies imply that cPA
      might be a therapeutic compound in the treatment of obesity and obesity-related
      diseases.

PMID- 21095183
TI  - Stable formyl peptide receptor agonists that activate the neutrophil NADPH
      oxidase identified through screening of a compound library.
AB  - The neutrophil formyl peptide receptors (FPR1 and FPR2) are G-protein coupled
      receptors that can induce pro-inflammatory as well as anti-inflammatory
      activities when activated. Accordingly, these receptors may become therapeutic
      targets for the development of novel drugs to be used for reducing the
      inflammation induced injuries in asthma, rheumatoid arthritis, Alzheimer's
      disease, cardiovascular diseases and traumatic shock. We screened a library of
      more then 50K small compounds for an ability of the compounds to induce a
      transient rise in intracellular Ca(2+) in cells transfected to express FPR2
      (earlier called FPRL1 or the lipoxin A(4) receptor). Ten agonist hits were
      selected for further analysis representing different chemical series and five new
      together with five earlier described molecules were further profiled. Compounds 1
      10 gave rise to a calcium response in the FPR2 transfectants with EC(50) values
      ranging from 4*10(-9)M to 2*10(-7)M. All 10 compounds activated human neutrophils
      to release superoxide, and based on the potency of their activity, the three most
      potent activators of the neutrophil NADPH-oxidase were further characterized.
      These three agonists were largely resistant to inactivation by neutrophil
      produced reactive oxygen species and shown to trigger the same functional
      repertoire in neutrophils as earlier described peptide agonists. Accordingly they
      induced chemotaxis, granule mobilization and secretion of superoxide.
      Interestingly, the oxidase activity was largely inhibited by cyclosporine H, an
      FPR1 selective antagonist, but not by PBP10, an FPR2 selective inhibitor,
      suggesting that FPR1 is the preferred receptor in neutrophils for all three
      agonists.

PMID- 21095184
TI  - First molecular identification of Sarcocystis miescheriana (Protozoa,
      Apicomplexa) from wild boar (Sus scrofa) in Iran.
AB  - Sarcocystis isolate obtained from the thigh muscle of a wild boar (Sus scrofa),
      captured from Gilan Province, northern Iran, was subjected to molecular analysis.
      Genomic DNA was obtained using a DNA extraction tissue kit and Polymerase chain
      reaction (PCR) for amplification of the 18S ribosomal DNA region yielded an 842
      bp DNA band on agarose gel. Analysis of DNA sequencing by BLAST confirmed the
      isolate as Sarcocystis miescheriana and the sequence was deposited in GenBank by
      Accession No. GU395554. This is the first molecular identification of an isolate
      of S. miescheriana in Iran.

PMID- 21095185
TI  - Echinococcus multilocularis: identification and functional characterization of
      cathepsin B-like peptidases from metacestode.
AB  - Cysteine peptidases have potent activities in the pathogenesis of various
      parasitic infections, and are considered as targets for chemotherapy and antigens
      for vaccine. In this study, two cathepsin B-like cysteine peptidases (EmCBP1 and
      EmCBP2) from Echinococcus multilocularis metacestodes were identified and
      characterized. Immunoblot analyses demonstrated that EmCBP1 and EmCBP2 were
      present in excretory/secretory products and extracts of E. multilocularis
      metacestodes. By immunohistochemistry, EmCBP1 and EmCBP2 were shown to localize
      to the germinal layer, the brood capsule and the protoscolex. Recombinant EmCBP1
      and EmCBP2 expressed in Pichia pastoris, at optimum pH 5.5, exhibited substrate
      preferences for Z-Phe-Arg-MCA, Z-Val-Val-Arg-MCA, and Z-Leu-Arg-MCA, and low
      levels of hydrolysis of Z-Arg-Arg-MCA. Furthermore, recombinant enzymes degraded
      IgG, albumin, type I and IV collagens, and fibronectin. These results suggested
      that EmCBP1 and EmCBP2 may play key roles in protein digestion for parasites'
      nutrition and in parasite-host interactions.

PMID- 21095186
TI  - Plasmodium falciparum: differing effects of non-esterified fatty acids and
      phospholipids on intraerythrocytic growth in serum-free medium.
AB  - Different combinations of non-esterified fatty acids (NEFA) had variable effects
      on intraerythrocytic growth of Plasmodium falciparum. All stages of the parasite
      cultured in medium supplemented with cis-9-octadecenoic acid (C18:1-cis-9),
      hexadecanoic acid (C16:0), phospholipids (Pld) and bovine albumin free of NEFA
      were similar to those grown in complete growth medium. Three typical growth
      patterns indicating suppressed schizogony (SS), suppressed formation of
      merozoites (SMF), and inhibited invasion of merozoites (IMI) resulted from
      culture in other combinations of lipids. Unsaturated or saturated NEFA with
      longer or shorter carbon chains than C18:1-cis-9 or C16:0, higher degree of
      unsaturation, and trans-forms mainly resulted in SS and SMF effects. However, IMI
      or partial IMI was observed with tetradecanoic acid or octadecanoic acid enriched
      with C18:1-cis-9, and cis-9-hexadecenoic acid plus C16:0. Isoforms of C18:1-cis-9
      also mainly resulted in partial IMI. SMF also occurred with C18:1-cis-9 plus
      C16:0 in the absence of Pld. Thus different NEFA exerted distinct roles in
      erythrocytic growth of the parasite by sustaining development at different
      stages.

PMID- 21095187
TI  - Investigation of some medicinal plants traditionally used for treatment of
      malaria in Kenya as potential sources of antimalarial drugs.
AB  - Malaria is a major public health problem in many tropical and subtropical
      countries and the burden of this disease is getting worse, mainly due to the
      increasing resistance of Plasmodium falciparum against the widely available
      antimalarial drugs. There is an urgent need for discovery of new antimalarial
      agents. Herbal medicines for the treatment of various diseases including malaria
      are an important part of the cultural diversity and traditions of which Kenya's
      biodiversity has been an integral part. Two major antimalarial drugs widely used
      today came originally from indigenous medical systems, that is quinine and
      artemisinin, from Peruvian and Chinese ancestral treatments, respectively. Thus
      ethnopharmacology is a very important resource in which new therapies may be
      discovered. The present review is an analysis of ethnopharmacological
      publications on antimalarial therapies from some Kenyan medicinal plants.

PMID- 21095188
TI  - IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3).
AB  - Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase vital to the regulation
      of T-cells. We report that JAK3 is a mediator of interleukin-8 (IL-8) stimulation
      of a different class of hematopoietic relevant cells: human neutrophils. IL-8
      induced a time- and concentration-dependent activation of JAK3 activity in
      neutrophils and differentiated HL-60 leukemic cells. JAK3 was more robustly
      activated by IL-8 than other kinases: p70S6K, mTOR, MAPK or PKC. JAK3 silencing
      severely inhibited IL-8-mediated chemotaxis. Thus, IL-8 stimulates chemotaxis
      through a mechanism mediated by JAK3. Further, JAK3 activity and chemotaxis were
      inhibited by the flavonoid apigenin (4',5,7-trihydroxyflavone) at ~5nM IC(50).
      These new findings lay the basis for understanding the molecular mechanism of
      cell migration as it relates to neutrophil-mediated chronic inflammatory
      processes.

PMID- 21095190
TI  - Functional argument for the existence of an avian nitric oxide synthase in muscle
      mitochondria: effect of cold acclimation.
AB  - We report the first evidence of a mitochondrial NO synthase (mtNOS) in bird
      skeletal muscle. In vitro, mtNOS activity stimulated by L-arginine reduced
      intermyofibrillar mitochondrial oxygen uptake and ATP synthesis rates, stimulated
      endogenous H(2)O(2) generation, but had no effect on oxidative phosphorylation
      efficiency. Arginine-induced effects were fully reversed by L-NAME, a known NOS
      inhibitor. When ducklings were cold exposed for 4 weeks, muscle mitochondria
      displayed an increased state 3 respiration, a reduced H(2)O(2) generation but no
      significant alteration in mtNOS activity. We conclude that mtNOS is expressed in
      avian skeletal muscle.

PMID- 21095189
TI  - Filamin A mediates interactions between cytoskeletal proteins that control cell
      adhesion.
AB  - Cell adhesion, spreading and migration on extracellular matrices are regulated by
      complex processes that involve the cytoskeleton and a large array of adhesion
      receptors, including the beta1 integrin. Filamin A is a large, multi-domain,
      homodimeric actin binding protein that contributes to the mechanical stability of
      cells and interacts with several proteins that regulate cell adhesion including
      beta1 integrin and several protein kinases. Here we review current data on the
      structure, mechanical properties and intracellular signaling functions of filamin
      that regulate cell adhesion. We also consider new data showing that interactions
      of filamin A with intermediate filaments and protein kinase C enable tight
      regulation of beta1 integrin function and consequently early events in cell
      adhesion and migration on extracellular matrix proteins.

PMID- 21095191
TI  - Regulation and distribution of squirrel monkey chorionic gonadotropin and
      secretogranin II in the pituitary.
AB  - Secretogranin II (SgII) is a member of the granin family of proteins found in
      neuroendocrine and endocrine cells. The expression and storage of SgII in the
      pituitary gland of Old World primates and rodents have been linked with those of
      luteinizing hormone (LH). However, New World primates including squirrel monkeys
      do not express LH in the pituitary gland, but rather CG is expressed. If CG takes
      on the luteotropic role of LH in New World primates, SgII may be associated with
      the expression and storage of CG in the pituitary gland. The goal of this study
      was to evaluate the regulation and distribution of CG and SgII in the squirrel
      monkey. A DNA fragment containing approximately 750 bp of squirrel monkey SgII
      promoter was isolated from genomic DNA and found to contain a cyclic-AMP response
      element that is also present in the human SgII promoter and important for GnRH
      responsiveness. The squirrel monkey and human SgII promoters were similarly
      activated by GnRH in luciferase reporter gene assays in LbetaT2 cells. Double
      immunofluorescence microscopy demonstrated close association of SgII and CG in
      gonadotrophs of squirrel monkey pituitary gland. These results suggest that CG
      and SgII have a similar intercellular distribution and are coregulated in
      squirrel monkey pituitary gland.

PMID- 21095192
TI  - Diurnal rhythms in hypothalamic/pituitary AVT synthesis and secretion in rainbow
      trout: evidence for a circadian regulation.
AB  - Arginine vasotocin (AVT) and isotocin (IT) are two neurohypophysial peptide
      hormones for which a role in adaptation to environmental changes has been
      suggested in fish. In teleosts, there are only a few available studies about
      circadian changes of AVT and IT levels, and a role of those peptides in the
      circadian system has been mainly suggested on the basis of the role of the
      homologous hormone AVP in mammals. Herein, we evaluated the diurnal rhythms in
      plasma AVT, pituitary AVT and IT content and the hypothalamic pro-vasotocin (pro
      VT) expression in rainbow trout kept under a natural photoperiod, as well as
      their persistence in constant darkness as a tool for defining circadian
      dependence. Trout kept under a natural light cycle showed clear diurnal rhythms
      in both circulating and pituitary AVT levels with peak values around the last
      hours of the light phase. Hypothalamic pro-VT mRNA was also rhythmically
      expressed with similar peak characteristics. These rhythms persisted in fish kept
      under constant darkness for nearly two consecutive days, although peaks were
      progressively attenuated and phase-advanced. An IT rhythm was also found in
      pituitary of the trout maintained under a natural photoperiod, but not in those
      kept under continuous darkness. These results suggest that rhythms of
      hypothalamic AVT synthesis might be regulated by endogenous circadian mechanisms,
      and these rhythms contribute to maintain a similar fluctuation in pituitary AVT
      secretion into the blood. A potential role for AVT in the circadian and seasonal
      time-keeping system of teleost fish, either as a component of the neural
      machinery that participates in the adaptation to cyclic environmental changes, or
      as a circadian/seasonal output signal, is also discussed.

PMID- 21095193
TI  - Cortisol and corticosterone exhibit different seasonal variation and responses to
      acute stress and captivity in tuco-tucos (Ctenomys talarum).
AB  - In this work we aimed to evaluate variations in plasma glucocorticoids (GCs,
      cortisol and corticosterone) levels throughout an annual cycle in free-living
      male tuco-tucos (Ctenomys talarum) and compare their responses to acute and
      chronic stressors (trapping, manipulation, immobilization, confinement in a novel
      environment, transference to captivity). In addition, we used leukocyte profiles
      to allow discrimination between basal and stress-induced seasonal changes in GC
      concentrations. Our results showed that cortisol and corticosterone are
      differently affected by environmental stimuli in C. talarum. Both hormones showed
      different patterns of variation in the field and responses to captivity.
      Moreover, only cortisol was responsive to acute stressors. Leukocyte profiles
      indicated that animals were unstressed in the field and therefore, that we were
      able to measure basal, stress-independent, fluctuations in GC levels. GC
      concentrations were low in comparison to values frequently reported for other
      mammals. Our results suggest differentiated physiological roles for cortisol and
      corticosterone in our study species and further emphasize the complexity of GC
      physiology in wild mammals.

PMID- 21095195
TI  - Transport mechanisms in oral transmucosal drug delivery: implications for pain
      management.
AB  - The mechanism for the oral transmucosal delivery of fentanyl citrate (OTFC) was
      investigated in this work. A developed mathematical model included the following
      transport characteristics: dissolution of the fentanyl citrate lozenge, diffusion
      through the saliva and oral mucosal membrane and equilibrium between adjacent
      layers. An orthogonal-collocation-based solution procedure was adopted to
      discretize the governing equations and boundary conditions. The Mathematica(r)
      built-in function, NDSolve, was applied to integrate the equations with respect
      to time. Simulations were conducted with a 200 MUg-dosage. A novel fabrication
      method, aimed at maintaining a high flux for a prolonged period of time, was
      proposed based on the calculated delivery rate and cumulative amount of
      medicament absorbed into the systemic circulation. The model allows drug
      manufacturers to decide when to replace the unit based on estimated drug
      concentrations in the saliva and the mucosal membrane. Both the model and
      solution strategies were validated using serum fentanyl citrate concentration
      collected from adult subjects. The predicted profiles, based on parameters
      obtained from the literature, agree well with the experimental data.

PMID- 21095194
TI  - Non-covalent interactions across subunit interfaces in Sm proteins.
AB  - The distinguishing property of Sm protein associations is their high stability.
      In order to understand this property, we analyzed the interface non-covalent
      interactions and compared the properties of the Sm protein interfaces with those
      of a test set, Binding Interface Database (BID). The comparison revealed that the
      main differences between interfaces of Sm proteins and those of the BID set are
      the content of charged residues, hydrogen bonds, salt bridges, and conservation
      scores of interface residues. In Sm proteins, the interfaces have more
      hydrophobic and fewer charged residues than the surface, which is also the case
      for the BID test set and other proteins. However, in the interfaces, the content
      of charged residues in Sm proteins (26%) is substantially larger than that in the
      BID set (22%). Both interfaces of Sm proteins and of test set have a similar
      number of hydrophobic interactions per 100A(2). The interfaces of Sm proteins
      have substantially more hydrogen bonds than the interfaces in test set. The
      results show clearly that the interfaces of Sm proteins form more salt bridges
      compared with test set. On average, there are about 16 salt bridges per
      interface. The high conservation score of amino acids that are involved in non
      covalent interactions in protein interfaces is an additional strong argument for
      their importance. The overriding conclusion from this study is that the non
      covalent interactions in Sm protein interfaces considerably contribute to
      stability of higher order structures. 

PMID- 21095196
TI  - Mutational and promoter hypermethylation status of FHIT gene in breast cancer
      patients of Kashmir.
AB  - OBJECTIVE: Fragile histidine triad (FHIT) gene located at chromosome 3p14.2 is a
      putative tumor suppressor gene involved in the pathogenesis of breast cancer.
      Both genetic and epigenetic alterations in FHIT have been implicated in breast
      carcinoma. In the present study, our main aim was to study the impact of these
      two kinds of alterations of FHIT gene in breast cancer patients of Kashmir.
      METHODS: We screened a total of 130 breast cancer patients of Kashmir by PCR-SSCP
      followed by direct sequencing and methylation specific PCR. RESULTS: Mutational
      screening of FHIT gene revealed significant amount of mutations [40.7% (53/130)]
      in five hot spot exons (exon 5-9), FHIT promoter was found to be hypermethylated
      in 59 of 130 [45.3%] breast cancer patients in our population. CONCLUSION: In the
      present study we have shown a significant association between the mutational and
      hypermethylation profile of FHIT gene. Hence, we provide the first evidence to
      our knowledge that the significant association of FHIT mutation and
      hypermethylation leads to the complete inactivation of FHIT gene in patients with
      breast cancer. Silencing of the FHIT gene by promoter hypermethylation occurs in
      breast carcinomas, especially those with the significant amount of mutations.

PMID- 21095197
TI  - Integration of tactile input across fingers in a patient with finger agnosia.
AB  - Finger agnosia has been described as an inability to explicitly individuate
      between the fingers, which is possibly due to fused neural representations of
      these fingers. Hence, are patients with finger agnosia unable to keep tactile
      information perceived over several fingers separate? Here, we tested a finger
      agnosic patient (GO) on two tasks that measured the ability to keep tactile
      information simultaneously perceived by individual fingers separate. In
      experiment 1 GO performed a haptic search task, in which a target (the absence of
      a protruded line) needed to be identified among distracters (protruded lines).
      The lines were presented simultaneously to the fingertips of both hands.
      Similarly to the controls, her reaction time decreased when her fingers were
      aligned as compared to when her fingers were stretched and in an unaligned
      position. This suggests that she can keep tactile input from different fingers
      separate. In experiment two, GO was required to judge the position of a target
      tactile stimulus to the index finger, relatively to a reference tactile stimulus
      to the middle finger, both in fingers uncrossed and crossed position. GO was able
      to indicate the relative position of the target stimulus as well as healthy
      controls, which indicates that she was able to keep tactile information perceived
      by two neighbouring fingers separate. Interestingly, GO performed better as
      compared to the healthy controls in the finger crossed condition. Together, these
      results suggest the GO is able to implicitly distinguish between tactile
      information perceived by multiple fingers. We therefore conclude that finger
      agnosia is not caused by minor disruptions of low-level somatosensory processing.
      These findings further underpin the idea of a selective impaired higher order
      body representation restricted to the fingers as underlying cause of finger
      agnosia.

PMID- 21095198
TI  - The executive control of attention differentiates patients with schizophrenia,
      their first-degree relatives and healthy controls.
AB  - Attentional and executive impairments have been reported in patients with
      schizophrenia and in their healthy first-degree relatives. However, its nature
      remains unclear and discrepancies between studies have been observed. These might
      be due to differences in the clinical severity of the illness or in
      sociodemographic factors. The objective of the present work was to explore the
      efficiency of three attention networks: alerting, orienting and executive control
      (conflict inhibition) defined anatomically, using patients, their relatives and
      controls, assessing the possibility to use them as endophenotypes. We used three
      tests, the Attention Network Test (ANT), the Wisconsin Card Sorting Test (WCST)
      and the Stroop Test, and compared 52 patients with schizophrenia, 55 of their
      first-degree relatives and 53 unrelated healthy controls, taking into account
      demographic variables (age, sex and years of education) and clinical symptoms of
      schizophrenia. Patients had a longer overall mean reaction-time (p<0.001), and
      took longer to resolve the ANT conflict (ANTc) (p=0.04) than the control group.
      In the schizophrenia group, the SSPI disorganization score was significantly
      correlated to the ANTc performance. Additionally, first-degree relatives of
      patients with schizophrenia also performed significantly worse than controls in
      attention performance test. Our findings support a specific deficit in executive
      control of attention in patients with schizophrenia. This deficit was shown to be
      correlated with the intensity of the disorganization score in patients. Relative
      presented an intermediate phenotype between patients and controls; the ANT
      reaction time (but not the ANTc) may thus be considered as possible endophenotype
      marker for schizophrenia.

PMID- 21095199
TI  - Neural structures and mechanisms involved in scene recognition: a review and
      interpretation.
AB  - Since the discovery in 1996 that a region within caudal parahippocampal cortex
      subserves learning and recall of topographical information, numerous studies
      aimed at elucidating the structures and pathways involved in scene recognition
      have been published. Neuroimaging studies, in particular, have revealed the
      locations and identities of some of the principal cortical structures that
      mediate these faculties. In the present study the detailed organization of the
      system is examined, based on a meta-analysis of neuroimaging studies of scene
      processing in human subjects, combined with reviews of the results of lesions on
      this type of processing, single neuron studies, and available hodological data in
      non-human primates. A cortical hierarchy of structures that mediate scene
      recognition is established based on these data, and an attempt is made to
      determine the function of the individual components of the system.

PMID- 21095201
TI  - Nitrite in feed: from animal health to human health.
AB  - Nitrite is widely consumed from the diet by animals and humans. However the
      largest contribution to exposure results from the in vivo conversion of
      exogenously derived nitrate to nitrite. Because of its potential to cause to
      methaemoglobin (MetHb) formation at excessive levels of intake, nitrite is
      regulated in feed and water as an undesirable substance. Forages and contaminated
      water have been shown to contain high levels of nitrate and represent the largest
      contributor to nitrite exposure for food-producing animals. Interspecies
      differences in sensitivity to nitrite intoxication principally result from
      physiological and anatomical differences in nitrite handling. In the case of
      livestock both pigs and cattle are relatively susceptible. With pigs this is due
      to a combination of low levels of bacterial nitrite reductase and hence potential
      to reduce nitrite to ammonia as well as reduced capacity to detoxify MetHb back
      to haemoglobin (Hb) due to intrinsically low levels of MetHb reductase. In cattle
      the sensitivity is due to the potential for high dietary intake and high levels
      of rumen conversion of nitrate to nitrite, and an adaptable gut flora which at
      normal loadings shunts nitrite to ammonia for biosynthesis. However when this
      escape mechanism gets overloaded, nitrite builds up and can enter the blood
      stream resulting in methemoglobinemia. Looking at livestock case histories
      reported in the literature no-observed-effect levels of 3.3mg/kg body weight
      (b.w.) per day for nitrite in pigs and cattle were estimated and related to the
      total daily nitrite intake that would result from complete feed at the EU maximum
      permissible level. This resulted in margins of safety of 9-fold and 5-fold for
      pigs and cattle, respectively. Recognising that the bulkiness of animal feed
      limits their consumption, these margins in conjunction with good agricultural
      practise were considered satisfactory for the protection of livestock health. A
      human health risk assessment was also carried out taking into account all direct
      and indirect sources of nitrite from the human diet, including carry-over of
      nitrite in animal-based products such as milk, eggs and meat products. Human
      exposure was then compared with the acceptable daily intake (ADI) for nitrite of
      0-0.07 mg/kg b.w. per day. Overall, the low levels of nitrite in fresh animal
      products represented only 2.9% of the total daily dietary exposure and thus were
      not considered to raise concerns for human health. It is concluded that the
      potential health risk to animals from the consumption of feed or to man from
      eating fresh animal products containing nitrite, is very low.

PMID- 21095200
TI  - Actual and perceived sleep: associations with daytime functioning among
      postpartum women.
AB  - Sleep and wake have a homeostatic relation that influences most aspects of
      physiology and waking behavior. Sleep disturbance has a detrimental effect on
      sleepiness and psychomotor vigilance. The purpose of this study was to identify
      which actual or perceived sleep characteristics accounted for the most variance
      in daytime functioning among postpartum mothers. Seventy first-time postpartum
      mothers' actual sleep (actigraphically estimated: total sleep time, number of
      wake bouts, length of nocturnal wake, and sleep efficiency) and perceived sleep
      (self-reported: number of awakenings, wake time, and sleep quality) were measured
      along with their daytime functioning (Stanford Sleepiness Scale [SSS], Epworth
      Sleepiness Scale [ESS], Visual Analogue of Fatigue Scale [VAFS], and morning
      Psychomotor Vigilance Test [PVT]). Data were repeatedly collected from the same
      sample during postpartum weeks 2, 7, and 13. Four stepwise linear regressions
      were calculated for each postpartum week to examine which objective and/or
      subjective variable(s) accounted for the most variance in daytime functioning.
      The SSS and VAFS were both most consistently associated with perceived sleep
      quality. The ESS was most consistently associated with actual total sleep time.
      PVT performance was most consistently associated with estimates of actual and
      perceived sleep efficiency. Actual and perceived sleep profiles were
      differentially associated with specific daytime functions. These results from
      postpartum mothers may indicate that populations who experience specific forms of
      sleep disturbance (e.g. fragmentation and/or deprivation) may also experience
      specific daytime conditions.

PMID- 21095202
TI  - Study of a novel glycoconjugate, thiopeptidoglycan, and a novel polysaccharide
      lyase, thiopeptidoglycan lyase.
AB  - A typical filamentous bacterium, Sphaerotilus natans, secretes a thiolic
      glycoconjugate which is assembled into a microtube, so called sheath. The
      glycoconjugate is known to consist of a pentasaccharide-dipeptide repeating unit,
      but its chemical structure has not been completely elucidated. In order to
      determine its chemical structure, the sheath was broken down by performic acid
      oxidation. The released sulfonated derivative was water soluble which was
      suitable for detailed NMR analysis. The data exhibited the presence of two
      stoichiometric and one substoichiometric (relative abundance was about 0.5)
      acetylations, suggesting that the glycoconjugate is composed of two equimolar
      pentasaccharide-dipeptide repeating units each having either two or three acetyl
      groups. However, the position of substoichiometric acetylation could not be
      defined. To determine the position, the sheath was derivatized with a thiol
      selective fluorescent reagent followed by digestion with a specific
      polysaccharide lyase prepared from a sheath-degrading bacterium, Paenibacillus
      koleovorans. As expected, two fluorescent digests were recovered by reverse-phase
      HPLC and were subjected to NMR analysis. The data revealed that both digests are
      pentasaccharide-dipeptides which have unsaturated glucuronic acid and
      galactosamine residues at their reducing and non-reducing ends, respectively. It
      was also confirmed that one digest has 3-O-acetylated glucose residue while the
      other has non-derivatized glucose residue. The substoichiometric acetylation was
      thus identified with the 3-O-acetylation, and structural determination of the
      thiolic glycoconjugate was completed. By virtue of the clarification of the two
      digests' structures, the cleavage site was specified as (1->4)-alpha
      galactosaminic bond to glucuronic acid. Based on the present and earlier
      findings, we propose a novel glycoconjugate category named thiopeptidoglycan and
      a novel polysaccharide lyase named thiopeptidoglycan lyase.

PMID- 21095203
TI  - Avian-specific TLRs and downstream effector responses to CpG-induction in chicken
      macrophages.
AB  - Chickens possess toll-like receptor (TLR15), a pattern recognition receptor (PRR)
      absent in mammals. We characterized the regulation and mechanism of CpG
      responsiveness via TLRs in chicken macrophage HD11 cells. TLR15 was significantly
      upregulated after induction with B- and C-type CpG oligonucleotides (ODN),
      tripalmitoylated lipopeptide (PAM3CSK4), Escherichia coli- and Salmonella
      enteritidis-derived lipopolysaccharide (LPS). In response to CpG-ODN inhibitor,
      TLR15 and IL1B were downregulated, but TLR21 was upregulated. IL1B was
      upregulated with CpG-ODN and downregulated after inhibitor treatment. The results
      suggest that responsiveness to different types of CpG-ODN in chicken macrophages
      requires multiple receptors, each with unique variation in expression. We
      utilized RNA interference (RNAi) technology to examine myeloid differentiation
      primary response gene (MyD88) dependency of TLR15 and TLR21. HD11 macrophages
      transfected with multiple MyD88-target siRNAs exhibited 70% decrease in MyD88
      mRNA expression. IL1B was upregulated with CpG induction in cells with no
      reduction of MyD88 mRNA levels, but not in cells with 70% MyD88 reduction.
      Therefore, induction through TLR15 in response to CpG-ODN operates via the MyD88
      dependent pathway in chicken macrophages.

PMID- 21095204
TI  - Acute phase response in Chinese soft-shelled turtle (Trionyx sinensis) with
      Aeromonas hydrophila infection.
AB  - Chinese soft-shelled turtle (Trionyx sinensis) is an important culture reptile.
      However, little is known about its acute phase response (APR) caused by bacteria.
      Serum amyloid A (SAA) is a major acute phase protein (APP). In this study, a
      turtle SAA homologue was identified and described in reptiles. The full-length
      cDNA of turtle SAA was 554 bp and contained a 381 bp open reading frame (ORF)
      coding for a protein of 127 aa. Similar to other known SAA genes, the turtle SAA
      gene contained three exons and two introns. The promoter region of turtle SAA
      gene contained the consensus binding sites for nuclear factor (NF)-kappaB and c
      Rel. The turtle SAA amino acid sequence shared the highest identity to avian SAA
      sequences. Meantime, we present the first systematic study with expression levels
      of five genes encoding APPs in immune response caused by Aeromonas hydrophila
      infection. After infection, turtle SAA mRNA was induced in liver at 8h, then
      increased more than 1200-fold at 2d; in spleen and kidney, the SAA mRNAs were
      also induced during 8h-7d, but the level was far lower than that in the liver.
      The complement 3 (C3), fibrinogen-gamma chain (Fb-G) and cathepsin L (CathL)
      mRNAs were increased in liver at 2d, whereas the albumin (ALB) mRNA was
      significantly decreased during 8h-7d. Our studies suggest that the APR in turtle
      with A. hydrophila infection is similar to that in mammals, and SAA is a major
      indicator of bacterial infection, especially at early stage, in reptiles.
      Additionally, the different expression patterns of five APP genes observed in
      present studies could provide clues for understanding the innate immune
      mechanisms in the APR of reptiles.

PMID- 21095205
TI  - Activity of Melaleuca alternifolia (tea tree) oil on Influenza virus A/PR/8:
      study on the mechanism of action.
AB  - Our previous study demonstrated that Melaleuca alternifolia (tea tree) oil (TTO)
      had an interesting antiviral activity against Influenza A in MDCK cells. In fact,
      when we tested TTO and some of its components, we found that TTO had an
      inhibitory effect on influenza virus replication at doses below the cytotoxic
      dose; terpinen-4-ol, terpinolene, and alfa-terpineol were the main active
      components. The aim of this study was to investigate the mechanism of action of
      TTO and its active components against Influenza A/PR/8 virus subtype H1N1 in MDCK
      cells. None of the test compounds showed virucidal activity nor any protective
      action for the MDCK cells. Thus, the effect of TTO and its active components on
      different steps of the replicative cycle of influenza virus was studied by adding
      the test compounds at various times after infection. These experiments revealed
      that viral replication was significantly inhibited if TTO was added within 2h of
      infection, indicating an interference with an early step of the viral replicative
      cycle of influenza virus. The influence of the compound on the virus adsorption
      step, studied by the infective center assay, indicated that TTO did not interfere
      with cellular attachment of the virus. TTO did not inhibit influenza virus
      neuraminidase activity, as shown by the experiment measuring the amount of 4
      methylumbelliferone, cleaved by the influenza virus neuraminidase from the
      fluorogenic substrate 2'-O-(4-methylumbelliferyl)-N-acetylneuraminic acid. The
      effect of TTO on acidification of cellular lysosomes was studied by vital
      staining with acridine orange using bafilomycin A1 as positive control. The
      treatment of cells with 0.01% (v/v) of TTO at 37 degrees C for 4h before staining
      inhibited the acridine orange accumulation in acid cytoplasmic vesicles,
      indicating that TTO could inhibit viral uncoating by an interference with
      acidification of intralysosomal compartment.

PMID- 21095207
TI  - Nucleolar localization/retention signal is responsible for transient accumulation
      of histone H2B in the nucleolus through electrostatic interactions.
AB  - The majority of known nuclear proteins are highly mobile. The molecular
      mechanisms by which they accumulate inside stable compartments that are not
      separated from the nucleoplasm by membranes are obscure. The compartmental
      retention of some proteins is associated with their biological function; however,
      some protein interactions within distinct nuclear structures may be non-specific.
      The non-specific retention may lead to the accumulation of proteins in distinct
      structural domains, even if the protein does not function inside this domain. In
      this study, we have shown that histone H2B-EGFP initially accumulated in the
      nucleolus after ectopic expression, and then gradually incorporated into the
      chromatin to leave only a small amount of nucleolus-bound histone that was
      revealed by removing chromatin-bound proteins with DNase I treatment. Nucleolar
      histone H2B had several characteristics: (i) it preferentially bound to granular
      component of the nucleolus and interacted with RNA or RNA-containing nucleolar
      components; (ii) it freely exchanged between the nucleolus and nucleoplasm; (iii)
      it associated with the nuclear matrix; and (iv) it bound to interphase prenuclear
      bodies that formed after hypotonic treatment. The region in histone H2B that acts
      as a nucleolar localization/retention signal (NoRS) was identified. This signal
      overlapped with a nuclear localization signal (NLS), which appears to be the
      primary function of this region. The NoRS activity of this region was non
      specific, but the molecular mechanism was probably similar to the NoRSs of other
      nucleolar proteins. All known NoRSs are enriched with basic amino acids, and we
      demonstrated that positively charged motifs (nona-arginine (R9) and nona-lysine
      (K9)) were sufficient for the nucleolar accumulation of EGFP. Also, the
      correlation between measured NoRS activity and the predicted charge was observed.
      Thus, NoRSs appear to achieve their function through electrostatic interactions
      with the negatively charged components of the nucleolus. Though these
      interactions are non-specific, the functionally unrelated retention of a protein
      can increase the probability of its interaction with specific and functionally
      related binding sites.

PMID- 21095206
TI  - Lung surfactant DPPG phospholipid inhibits vaccinia virus infection.
AB  - Vaccinia virus (VACV) was used as a surrogate of Variola virus (genus
      Orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection
      via the respiratory airway. Lung surfactant, a physiological barrier to infection
      encountered by the virus, is predominantly composed of phospholipids whose role
      during orthopoxvirus infection has not been investigated. An attenuated Lister
      strain, derived from the traditional smallpox vaccine and the Western Reserve
      (WR) strain, lethal for mice infected by the respiratory route, were examined for
      their ability to bind various surfactant phospholipids. Dipalmitoyl
      phosphatidylglycerol (DPPG) was found to interact with both VACV strains. DPPG
      incorporated in small unilamellar vesicle (SUV-DPPG) inhibited VACV cell
      infection, unlike other phospholipids tested. Both pre-incubation of virus with
      SUV-DPPG and pretreatment of the cell with SUV-DPPG inhibited cell infection.
      This specific DPPG effect was shown to be concentration and time dependent and to
      prevent the first step of the viral cycle, i.e. virus cell attachment. Cryo
      electron microscopy highlighted the interaction between the virus and SUV-DPPG.
      In the presence of the phospholipid, virus particles displayed a hedgehog-like
      appearance due to the attachment of lipid vesicles. Mice infected intranasally
      with VACV-WR pre-incubated with SUV-DPPG survived a lethal infection. These data
      suggest that DPPG in lung surfactant could reduce the amount of orthopoxvirus
      particles able to infect pneumocytes at the beginning of a respiratory poxvirus
      infection. The knowledge acquired during this study of virus-DPPG interactions
      may be used to develop novel chemotherapeutic strategies for smallpox.

PMID- 21095208
TI  - Molecular epidemiology of bovine leukemia virus associated with enzootic bovine
      leukosis in Japan.
AB  - Bovine leukemia virus (BLV) infection of cattle has been increasing yearly in
      Japan although several European countries have successfully eradicated the
      infection. In the present study, phylogenetic analysis on the env gene obtained
      from 64 tumor samples found in different regions in Japan was carried out in
      order to define the genetic background of BLV strains prevailing in the country.
      Most of the Japanese isolates were found to reside in the consensus cluster or
      genotype 1 of BLV strains (Rodriguez et al., 2009). Out of them, 21 isolates and
      10 isolates exhibited the identical sequences, respectively. Only one isolate was
      classified into the different genotype related to the US isolates. Analysis on
      the deduced amino acids of gp51 demonstrated the sequence diversity in the
      neutralizing domain. These data may indicate that two major populations of BLV
      prevailed throughout Japan, whereas antigenic variants also exist. It was further
      proved that multiple invasion of the genetically different BLV strains have
      occurred in Japan.

PMID- 21095210
TI  - Antibody derivatization and conjugation strategies: application in preparation of
      stealth immunoliposome to target chemotherapeutics to tumor.
AB  - A great deal of effort has been made over the years to develop liposomes that
      have targeting vectors (oligosaccharides, peptides, proteins and vitamins)
      attached to the bilayer surface. Most studies have focused on antibody conjugates
      since procedures for producing highly specific monoclonal antibodies are well
      established. Antibody conjugated liposomes have recently attracted a great deal
      of interest, principally because of their potential use as targeted drug delivery
      systems and in diagnostic applications. A number of methods have been reported
      for coupling antibodies to the surface of stealth liposomes. The objective of
      this review is to enumerate various strategies which are employed in the
      modification and conjugation of antibodies to the surface of stealth liposomes.
      This review also describes various derivatization techniques of lipids prior and
      after their use in the preparation of liposomes. The use of single chain variable
      fragments and affibodies as targeting ligands in the preparation of
      immunoliposomes is also discussed.

PMID- 21095211
TI  - Finishing the family meal. The interactional organisation of satiety.
AB  - This paper provides an extended review of psychological, sociological and
      interactional research on mealtimes and satiety (fullness), arguing for a focus
      on how fullness and finishing a meal is interactionally achieved. Drawing on
      three specimen data fragments from contrasting family settings, routinely used
      resources for pursuing completion and expressing satiety are described. We show
      how checks on completion are tailored to children according to their age, the
      intimate knowledge family members have of one another and attuned to
      contingencies, such as, whether there is a further course to be offered. Equally,
      that in teaching children how to eat together with others, the family also
      transmits and transforms all manner of other eating practices such as how to
      comply, or not, with requests to finish. A central aim of the article is to
      complement the many studies of satiety that have explained its physiological
      aspects by providing the familial logics that are expressed in bringing the meal
      to a close. We offer a suggestive analysis, based on conversation analytic
      principles, to illustrate our argument and to provide a starting point for
      further work in this field. Where bodies of work have previously used mealtimes
      as a convenient setting for accessing other social practices, this article turns
      its focus back toward the tasks of dining together.

PMID- 21095212
TI  - Food nanotechnology in the news. Coverage patterns and thematic emphases during
      the last decade.
AB  - For novel issues like food nanotechnology, media can play an important role in
      shaping the awareness and mental associations that underlie public opinion.
      Seeking to complement recent research exploring public opinion formation about
      food nanotechnology, this study tracks the evolution of U.S. newspaper coverage
      of food nanotechnology, identifying the descriptive and thematic traits that have
      characterized this coverage over time. We use a rigorous methodology to examine
      the levels of coverage, authorship patterns, and thematic emphases exhibited in
      the American journalistic narrative about this burgeoning application of
      nanoscience. Our findings indicate that U.S. newspaper coverage of food
      nanotechnology is relatively modest in terms of how often it has been covered,
      its thematic diversity, and the level of journalistic expertise from which it was
      produced. To our knowledge, this is the first study to empirically assess
      journalistic coverage of food nanotechnology.

PMID- 21095209
TI  - The search for new therapies for human cytomegalovirus infections.
AB  - Ganciclovir (GCV), the therapy of choice for human cytomegalovirus (CMV)
      infections and foscarnet, a drug used to treat GCV-resistant CMV infections was
      approved more than twenty years ago. Although cidofovir and a prodrug of GCV have
      since been added to the armamentarium, a highly effective drug without
      significant toxicities has yet to be approved. Such a therapeutic agent is
      required for treatment of immunocompromised hosts and infants, which bear the
      greatest burden of disease. The modest antiviral activity of existing drugs is
      insufficient to completely suppress viral replication, which results in the
      selection of drug-resistant variants that remain pathogenic, continue to
      replicate, and contribute to disease. Sustained efforts, largely in the biotech
      industry and academia, have identified highly active lead compounds that have
      progressed into clinical studies with varying levels of success. A few of these
      compounds inhibit new molecular targets, remain effective against isolates that
      have developed resistance to existing therapies, and promise to augment existing
      therapies. Some of the more promising drugs will be discussed with an emphasis on
      those progressing to clinical studies. Their antiviral activity both in vitro and
      in vivo, spectrum of antiviral activity, and mechanism of action will be reviewed
      to provide an update on the progress of potential new therapies for CMV
      infections.

PMID- 21095214
TI  - Mirtazapine augmentation enhances cognitive and reduces negative symptoms in
      schizophrenia patients treated with risperidone: a randomized controlled trial.
AB  - This preliminary study aimed to determine if adding mirtazapine to risperidone
      might improve negative and cognitive symptoms in schizophrenia. In an 8-week,
      double-blind clinical trial, we randomly assigned 21 stabilized outpatients with
      schizophrenia undergoing risperidone treatment to adjunctive treatment with
      either mirtazapine or a placebo. The mirtazapine group exhibited a statistically
      significant improvement in cognitive function, including vocabulary and immediate
      memory, and negative symptoms (as measured by negative symptom scales) and showed
      an adverse effect of 5.83 kg mean weight gain. This study suggests augmenting
      risperidone with mirtazapine can effectively improve both negative and some
      cognitive symptoms of schizophrenia.

PMID- 21095213
TI  - Hydrogen sulfide reduces mRNA and protein levels of beta-site amyloid precursor
      protein cleaving enzyme 1 in PC12 cells.
AB  - Hydrogen sulfide (H(2)S) is now identified as a new neuromodulator. Increasing
      evidence suggest that H(2)S may play an important role in the progression of
      Alzheimer's disease (AD). The aim of the present study is to investigate the
      effects of H(2)S on beta-site amyloid precursor protein cleaving enzyme 1 (BACE
      1) expression and amyloid beta (Abeta) secretion in PC12 cells. The levels of
      BACE-1 mRNA were measured by quantitative polymerase chain reaction analysis.
      BACE-1 protein levels were assessed by Western blot. Cellular culture medium
      levels of Abeta1-42 were analyzed by ELISA. We found that sodium hydrosulfide
      (NaHS), a H(2)S donor, decreased BACE-1 mRNA and protein levels and Abeta1-42
      release. Furthermore, NaHS promoted the phosphorylation of Akt and ERK but not
      JNK or p38 MAPK. However, the effects of NaHS on BACE-1 expression and Abeta1-42
      secretion were abolished by inhibitors of phosphatidylinositol 3-kinase (PI3-K),
      but not of mitogen-activated protein kinase kinases (MEK). Our data indicate that
      H(2)S reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt
      signaling pathways. H(2)S releasing drugs may have therapeutic potential in AD
      patients.

PMID- 21095215
TI  - Gender differences in the effects of peroxisome proliferator-activated receptor
      gamma2 gene polymorphisms on metabolic adversity in patients with schizophrenia
      or schizoaffective disorder.
AB  - OBJECTIVE: Metabolic syndrome (MS) is a major health problem in schizophrenic
      patients. Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is one
      of the candidate genes responsible for the liability to metabolic problems. In
      this study, we investigated the effect of the PPARgamma2 gene Pro12Ala and C161T
      polymorphisms on metabolic adversities in patients with schizophrenia or
      schizoaffective disorder. METHODS: Metabolic profiles and PPARgamma2 gene
      polymorphisms were determined in 600 patients (309 men and 291 women) with a
      clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic
      indices and components of MS were compared between patients with different
      Pro12Ala or C161T genotypes. RESULTS: In the whole population, the allele
      frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms
      had no significant effect on obesity or metabolic-related traits. However,
      following gender stratification of the data, we found female 12Ala allele
      carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI =
      1.1-14.2, p = 0.04) and hypertension (OR=2.9, 95% CI = 1.2-7.4, p = 0.02) than
      female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin
      levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p =
      0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele
      carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and
      systolic blood pressure (p = 0.01), and were at greater risk of developing
      hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed
      that PPARgamma2 gene polymorphisms were significantly associated with HDL-C level
      in men and blood pressure in women. CONCLUSIONS: We did not find an association
      of PPARgamma2 gene polymorphisms with MS or obesity in our schizophrenia sample.
      But further analyses by gender stratification revealed gender-specific
      differences in the effect of different PPARgamma2 genotypes on certain metabolic
      adversities in these patients.

PMID- 21095216
TI  - Aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin enhances
      liver damage in bile duct-ligated mice.
AB  - The environmental pollutant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) is known
      to cause a wide variety of toxic effects, including hepatotoxicity, by way of the
      aryl hydrocarbon receptor (AHR). Although inducible expression of cytochrome P450
      (CYP) 1A1 and CYP1A2 is associated with liver injury caused by high-dose TCDD,
      the specific role of the AHR-CYP1 cascade in hepatotoxicity remains unclear. We
      investigated the effects of AHR activation under conditions of cholestasis. We
      administered oral TCDD to mice at a dose that can effectively induce Cyp1 gene
      expression without overt liver toxicity and then ligated their bile ducts. TCDD
      pretreatment enhanced bile duct ligation (BDL)-induced increases in liver and
      plasma bile acids, bilirubin, and aminotransferases. Histology of TCDD-pretreated
      BDL mice revealed massive hepatic necrosis without any increase in number of
      apoptotic cells. Whereas induction of AHR-target genes by TCDD was observed
      similarly in sham-operated as well as in BDL mice, TCDD pretreatment of BDL mice
      altered the expression of hepatic genes involved in bile acid synthesis and
      transport. Increased plasma proinflammatory cytokines, tumor necrosis factor and
      interleukin-1beta, in BDL mice were further elevated by TCDD pretreatment. Liver
      injury by TCDD plus BDL, such as increased plasma bile acids, bilirubin and
      aminotransferases, liver necrosis, and increased tumor necrosis factor
      production, was exaggerated in Cyp1a1/1a2(-/-) double knockout mice. These
      findings indicate that TCDD aggravates cholestatic liver damage and that the
      presence of CYP1A1 and CYP1A2 plays a protective role in liver damage caused by
      TCDD and BDL.

PMID- 21095217
TI  - Hepatoprotective activity of berberine is mediated by inhibition of TNF-alpha,
      COX-2, and iNOS expression in CCl(4)-intoxicated mice.
AB  - This study investigated the protective effects of isoquinoline alkaloid berberine
      on the CCl(4)-induced hepatotoxicity in mice. Berberine was administered as a
      single dose at 5 and 10mg/kg intraperitoneally (i.p.), 1h before CCl(4) (10%, v/v
      in olive oil, 2ml/kg) injection and mice were euthanized 24h later. The rise in
      serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      and alkaline phosphatase (ALP) in CCl(4)-intoxicated mice was markedly suppressed
      by berberine in a concentration-dependent manner. The decrease in hepatic
      activity of superoxide dismutase (Cu/Zn SOD) and an increase in lipid
      peroxidation were significantly prevented by berberine. Histopathological changes
      were reduced and the expression of tumor necrosis factor-alpha (TNF-alpha),
      cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was markedly
      attenuated by berberine 10mg/mg. The results of this study indicate that
      berberine could be effective in protecting the liver from acute CCl(4)-induced
      injury. The hepatoprotective mechanisms of berberine may be related to the free
      radical scavenging and attenuation of oxidative/nitrosative stress, as well as to
      the inhibition of inflammatory response in the liver.

PMID- 21095219
TI  - Mathematical modeling of cell cycle regulation in response to DNA damage:
      exploring mechanisms of cell-fate determination.
AB  - After DNA damage, cells activate p53, a tumor suppressor gene, and select a cell
      fate (e.g., DNA repair, cell cycle arrest, or apoptosis). Recently, a p53
      oscillatory behavior was observed following DNA damage. However, the relationship
      between this p53 oscillation and cell-fate selection is unclear. Here, we present
      a novel model of the DNA damage signaling pathway that includes p53 and whole
      cell cycle regulation and explore the relationship between p53 oscillation and
      cell fate selection. The simulation run without DNA damage qualitatively realized
      experimentally observed data from several cell cycle regulators, indicating that
      our model was biologically appropriate. Moreover, the comprehensive sensitivity
      analysis for the proposed model was implemented by changing the values of all
      kinetic parameters, which revealed that the cell cycle regulation system based on
      the proposed model has robustness on a fluctuation of reaction rate in each
      process. Simulations run with four different intensities of DNA damage, i.e. Low
      damage, Medium-damage, High-damage, and Excess-damage, realized cell cycle arrest
      in all cases. Low-damage, Medium-damage, High-damage, and Excess-damage
      corresponded to the DNA damage caused by 100, 200, 400, and 800 J/m(2) doses of
      UV-irradiation, respectively, based on expression of p21, which plays a crucial
      role in cell cycle arrest. In simulations run with High-damage and Excess-damage,
      the length of the cell cycle arrest was shortened despite the severe DNA damage,
      and p53 began to oscillate. Cells initiated apoptosis and were killed at 400 and
      800 J/m(2) doses of UV-irradiation, corresponding to High-damage and Excess
      damage, respectively. Therefore, our model indicated that the oscillatory mode of
      p53 profoundly affects cell fate selection.

PMID- 21095218
TI  - Mining Dense Overlapping Subgraphs in weighted protein-protein interaction
      networks.
AB  - Many methods have been proposed for mining protein complexes from a protein
      protein interaction network; however, most of them focus on unweighted networks
      and cannot find overlapping protein complexes. Since one protein may serve
      different roles within different functional groups, mining overlapping protein
      complexes in a weighted protein-protein interaction network has attracted more
      and more attention recently. In this paper, we propose an effective method,
      called MDOS (Mining Dense Overlapping Subgraphs), for mining dense overlapping
      protein complexes (subgraphs) in a weighted protein-protein interaction network.
      The proposed method can integrate the information about known complexes into a
      weighted protein-protein interaction network to improve the mining results. The
      experiment results show that our method mines more known complexes and has higher
      sensitivity and accuracy than the CODENSE and MCL methods.

PMID- 21095220
TI  - 16alpha-hydroxyprogesterone: origin, biosynthesis and receptor interaction.
AB  - The metabolism of progesterone (PROG) by cytochrome P450 17alpha
      hydroxylase/17,20-lyase (CYP17A1) results in the formation of both 17alpha
      hydroxyprogesterone (17-OHPROG) and 16alpha-hydroxyprogesterone (16-OHPROG) in
      humans. Unlike 17-OHPROG, 16-OHPROG is not metabolised further in steroidogenic
      tissue. While this metabolite can be readily detected in serum and urine, its
      physiological role remains unclear. This paper reviews the production of 16
      OHPROG by human CYP17A1 by providing insight into the catalysis of PROG by
      CYP17A1 and highlights the role of Ala105 in the 16alpha-hydroxylation reaction.
      As 16-OHPROG has been putatively linked to reproductive function, we investigated
      the interaction of this steroid metabolite with both isoforms of the human
      progesterone receptor (hPR). We show for the first time that 16-OHPROG can bind
      to both hPR-A and hPR-B and act as an agonist for both receptors.

PMID- 21095221
TI  - The thyroid hormone responsive protein (THRP) has a critical role in the
      embryogenesis of Xenopus laevis.
AB  - The human and mouse homologs of the rat thyroid hormone responsive protein
      (THRP), c-abl-interacting protein 2 (Abi-2), are critically involved in
      neurological development. The Abi-2 gene is evolutionarily conserved in
      vertebrates, and is also found in Xenopus laevis and Drosophila melanogaster. The
      THRP gene is one of the few genes regulated by thyroid hormone in adult animals.
      Sequence analysis of the 5'-flanking region of the THRP gene identified a
      putative thyroid hormone response element (TRE) that is conserved between rat and
      human. To determine whether or not THRP regulates neural growth and development,
      THRP was constitutively expressed in transgenic X. laevis. Growth of most animals
      was halted in early neurulation while the few animals that survived the process
      developed into grossly malformed tadpoles. In contrast, control animals reached
      late embryonic stage 25. These observations suggest that THRP over-expression in
      early development is not compatible with completion of early embryogenesis and
      that a different strategy needs to be employed to investigate THRP function in
      this model.

PMID- 21095222
TI  - Evaluation of antioxidant activity of vanillin by using multiple antioxidant
      assays.
AB  - BACKGROUND: Vanillin, a compound widely used in foods, beverages, cosmetics and
      drugs, has been reported to exhibit multifunctional effects such as
      antimutagenic, antiangiogenetic, anti-colitis, anti-sickling, and antianalgesic
      effects. However, results of studies on the antioxidant activity of vanillin are
      not consistent. METHODS: We systematically evaluated the antioxidant activity of
      vanillin using multiple assay systems. DPPH radical-, galvinoxyl radical-, and
      ABTS(+)-scavenging assays, ORAC assay and an oxidative hemolysis inhibition assay
      (OxHLIA) were used for determining the antioxidant activity. RESULTS AND
      CONCLUSION: Vanillin showed stronger activity than did ascorbic acid and Trolox
      in the ABTS(+)-scavenging assay but showed no activity in the DPPH radical- and
      galvinoxyl radical-scavenging assays. Vanillin showed much stronger antioxidant
      activity than did ascorbic acid and Trolox in the ORAC assay and OxHLIA. In the
      ABTS(+)-scavenging assay, ORAC assay and OxHLIA, vanillin reacted with radicals
      via a self-dimerization mechanism. The dimerization contributed to the high
      reaction stoichiometry against ABTS(+) and AAPH-derived radicals to result in the
      strong effect of vanillin. Oral administration of vanillin to mice increased the
      vanillin concentration and the antioxidant activity in plasma. These data
      suggested that antioxidant activity of vanillin might be more beneficial than has
      been thought for daily health care. GENERAL SIGNIFICANCE: Based on the results of
      the present study, we propose the addition of antioxidant capacity to the
      multifunctionality of vanillin.

PMID- 21095223
TI  - Mechanical influence of static versus dynamic loadings on parametrical analysis
      of plasticized ethyl cellulose films.
AB  - The object of this study was to investigate the influence of static and dynamic
      forces on mechanical properties of the biocompatible polymer ethyl cellulose.
      Similar polymeric films containing 40% (w/w) of the plasticizer dibutyl sebacate
      were subjected to tensile forces at different velocities. The average Young's
      modulus and the variation of yield strength, strain, and strain energy at
      different velocities complied with the pre-established theories of dynamic
      loadings. The ultimate strength and the yield strength and/or strain displayed
      linearity with the velocity, though the ultimate strain and therefore, the
      plastic and/or ultimate working energies proved non-linear pseudo-Michaelis
      Menten behavior. The speculation was that achieving the maximum displacement
      would probably be the most important cause of failure. Finally the most suitable
      velocity at which the data would obtain the most demonstrable stress-strain
      diagrams was selected: tensile forces at almost low velocities, best illustrated
      as static forces, proved immature failure of the specimens during or shortly
      after the yield; so that the specimen resembled as a brittle material. High
      velocities of loadings were also avoided since the strain would usually approach
      the plateau and would therefore disrupt the rational correlation between forces
      and displacements during the end region of the curve.

PMID- 21095224
TI  - Modelling drug release from inert matrix systems: from moving-boundary to
      continuous-field descriptions.
AB  - The purpose of this review is to provide a comprehensive overview of mathematical
      procedures that can be used to describe the release of drugs from inert matrix
      systems. The review focuses on general principles rather than particular
      applications. The inherent multiscale nature of the drug-release process is
      pointed out and multiscale modelling is exemplified for inert porous matrices.
      Although effects of stagnant layers and finite volumes of release media are
      briefly discussed, the systematic analysis is restricted to systems under sink
      conditions. When the initial drug loading exceeds the drug solubility in the
      matrix, Higuchi-type moving-boundary descriptions continue to be highly valuable
      for obtaining approximate analytical solutions, especially when coupled with
      integral balance methods. Continuous-field descriptions have decisive advantages
      when numerical solutions are sought. This is because the mathematical formulation
      reduces to a diffusion equation with a nonlinear source term, valid over the
      entire matrix domain. Solutions can thus be effortlessly determined for arbitrary
      geometries using standard numerical packages.

PMID- 21095225
TI  - Gastroretentive drug delivery systems with L-dopa based on carrageenans and
      hydroxypropylmethylcellulose.
AB  - A comprehensive study was conducted to investigate the effects of carrageenans,
      and hydroxypropylmethylcellulose (HPMC) on the properties of hydrodynamically
      balanced systems (HBS) containing L-dopa as a model drug. The novel integrated
      approach included measurements of: solvent uptake, erosion, apparent density and
      changes in the internal structure of dosage forms during dissolution test by
      means of a USP4 compatible MRI. Differences in water ingress into the matrices
      with pure carrageenans (iota, kappa, lambda) or low viscous HPMC, were detected
      by non-invasive magnetic resonance imaging. Matrices based on carrageenans
      subjected to rapid hydration and erosion, were not able to maintain satisfactory
      floating properties for a sufficiently long period of time. The application of
      carrageenans in mixtures with HMC promoted water uptake by HBS formulations. The
      effect produced by varying the polymer blend's composition on release of the L
      dopa was also studied. Dissolution data was fitted to Korsmeyer-Peppas equation.
      For matrices containing mixtures of carrageenan and HPMC, the linear increase in
      the releasing rate constant, K, with the carrageenan content in the matrix was
      observed.

PMID- 21095227
TI  - Chronic exposure to cigarette smoke condensate in vitro induces epithelial to
      mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
AB  - Cigarette smoke causes lung tumorigenesis; however, the mechanisms underlying
      transformation are unknown. We investigated if tobacco compounds induce DNA
      promoter hypermethylation in BEAS-2B cells treated with low doses of cigarette
      smoke condensate (CSC) for one month. Transcriptional profiles and anchorage
      independent growth were explored using Affymetrix microarray and soft agar assay,
      respectively. To investigate if tobacco compounds induce hypermethylation,
      CSC/dimethyl sulfoxide (DMSO)-treated cells were further treated with 5-Aza-2'
      deoxycytidine (5AzaC) and trychostatin A (TSA). This treatment was followed by
      transcriptional profiling. CSC-exposed cells acquired a fibroblast-like shape
      with enhanced anchorage-independent growth. Silencing of epithelial cadherin, the
      hallmark of epithelial to mesenchymal transition (EMT), was observed upon
      exposure to CSC. Changes in the expression of genes involved in epidermal
      development, intercellular junction formation, and cytoskeleton formation were
      identified. Gene expression profiles from 5AzaC- and TSA-treated cells revealed
      130 genes possibly methylated due to chronic CSC exposure. Our results suggest
      that E-cadherin may also be silenced by hypermethylation in an in vitro model of
      chronic exposure to low doses of CSC. This study demonstrates evidence for a
      tobacco compound induced EMT-like process in vitro and provides insight into
      possible mechanisms of gene silencing occurring during this treatment.

PMID- 21095226
TI  - Changes in growth-related kinases in head, neck and limb muscles with age.
AB  - Sarcopenia coincides with declines in several systemic processes that signal
      through the MAP kinase and Akt-mTOR-p70S6k cascades typically associated with
      muscle growth. Effects of aging on these pathways have primarily been examined in
      limb muscles, which experience substantial activity and neural changes in
      addition to systemic hormonal and metabolic changes. Head and neck muscles are
      reported to undergo reduced sarcopenia and disuse with age relative to limb
      muscles, suggesting muscle activity may contribute to maintaining mass with age.
      However many head and neck muscles derive from embryonic branchial arches, rather
      than the somites from which limb muscles originate, suggesting that developmental
      origin may be important. This study compares the expression and phosphorylation
      of MAP kinase and mTOR networks in head, neck, tongue, and limb muscles from 8-
      and 26-month old F344 rats to test the hypothesis that physical activity and
      developmental origin contribute to preservation of muscle mass with age.
      Phosphorylation of p38 was exaggerated in aged branchial arch muscles.
      Phosphorylation of ERK and p70S6k T421/S424 declined with age only in the biceps
      brachii. Expression of p70S6k declined in all head and neck, tongue and limb
      muscles although no change in phosphorylation of p70S6k on T389 could be
      resolved. A systemic change that results in a loss of p70S6k protein expression
      may reduce the capacity to respond to acute hypertrophic stimuli, while the
      exaggerated p38 signaling in branchial arch muscles may reflect more active
      muscle remodeling.

PMID- 21095228
TI  - Crystallographic analysis of a thermoactive nitrilase.
AB  - The nitrilase superfamily is a large and diverse superfamily of enzymes that
      catalyse the cleavage of various types of carbon-nitrogen bonds using a Cys-Glu
      Lys catalytic triad. Thermoactive nitrilase from Pyrococcus abyssi (PaNit)
      hydrolyses small aliphatic nitriles like fumaro- and malononitryl. Yet, the
      biological role of this enzyme is unknown. We have analysed several crystal
      structures of PaNit: without ligands, with an acetate ion bound in the active
      site and with a bromide ion in the active site. In addition, docking calculations
      have been performed for fumaro- and malononitriles. The structures provide a
      proof for specific binding of the carboxylate ion and a general affinity for
      negatively changed ligands. The role of residues in the active site is considered
      and an enzymatic reaction mechanism is proposed in which Cys146 acts as the
      nucleophile, Glu42 as the general base, Lys113/Glu42 as the general acid, WatA as
      the hydrolytic water and Nzeta_Lys113 and N_Phe147 form the oxyanion hole.

PMID- 21095229
TI  - Statistical parametric network analysis of functional connectivity dynamics
      during a working memory task.
AB  - Network analysis has become a tool of choice for the study of functional and
      structural Magnetic Resonance Imaging (MRI) data. Little research, however, has
      investigated connectivity dynamics in relation to varying cognitive load. In
      fMRI, correlations among slow (<0.1 Hz) fluctuations of blood oxygen level
      dependent (BOLD) signal can be used to construct functional connectivity
      networks. Using an anatomical parcellation scheme, we produced undirected
      weighted graphs linking 90 regions of the brain representing major cortical gyri
      and subcortical nuclei, in a population of healthy adults (n=43). Topological
      changes in these networks were investigated under different conditions of a
      classical working memory task - the N-back paradigm. A mass-univariate approach
      was adopted to construct statistical parametric networks (SPNs) that reflect
      significant modifications in functional connectivity between N-back conditions.
      Our proposed method allowed the extraction of 'lost' and 'gained' functional
      networks, providing concise graphical summaries of whole-brain network
      topological changes. Robust estimates of functional networks are obtained by
      pooling information about edges and vertices over subjects. Graph thresholding is
      therefore here supplanted by inference. The analysis proceeds by firstly
      considering changes in weighted cost (i.e. mean between-region correlation) over
      the different N-back conditions and secondly comparing small-world topological
      measures integrated over network cost, thereby controlling for differences in
      mean correlation between conditions. The results are threefold: (i) functional
      networks in the four conditions were all found to satisfy the small-world
      property and cost-integrated global and local efficiency levels were
      approximately preserved across the different experimental conditions; (ii)
      weighted cost considerably decreased as working memory load increased; and (iii)
      subject-specific weighted costs significantly predicted behavioral performances
      on the N-back task (Wald F=13.39,df(1)=1,df(2)=83,p<0.001), and therefore
      conferred predictive validity to functional connectivity strength, as measured by
      weighted cost. The results were found to be highly sensitive to the frequency
      band used for the computation of the between-region correlations, with the
      relationship between weighted cost and behavioral performance being most salient
      at very low frequencies (0.01-0.03 Hz). These findings are discussed in relation
      to the integration/specialization functional dichotomy. The pruning of functional
      networks under increasing cognitive load may permit greater modular
      specialization, thereby enhancing performance.

PMID- 21095230
TI  - Processing social aspects of human gaze: a combined fMRI-DTI study.
AB  - Human gaze is a critical social cue that can reveal intentions and dispositions
      of others. The right posterior superior temporal sulcus (pSTS) is thought to be
      critically involved in processing eye gaze information. We combined diffusion
      tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to identify
      direct neural connections of right pSTS and to determine how these connections
      are modulated by the social significance of perceived gaze shifts. Participants
      saw faces with direct or averted gaze during event-related fMRI. Half of these
      faces remained static, and half displayed a dynamic gaze shift either towards or
      away from the subject. Social attention (dynamic gaze shifts towards the
      observer) not only increased activity in right pSTS, but also its functional
      connectivity with the right anterior insula (aIns) and right fusiform gyrus (FG).
      However, direct fiber connections from pSTS were demonstrated by DTI for the
      right aIns, but not the right FG. Moreover, the right FG responded to eye motion
      irrespective of direction and social significance; whereas the right aIns was
      selectively sensitive to social significance (i.e. gaze shifts towards the
      observer), but not generally to eye motion. We conclude that the social aspects
      of mutual gaze contact are processed by direct fiber pathways between right pSTS
      and right aIns; whereas increased connectivity with FG could reflect an enhanced
      perceptual analysis of changing facial features in dynamic gaze conditions and
      involves indirect fiber pathways with pSTS, perhaps via motion-selective regions
      in middle temporal (MT) gyrus that exhibited strong white-matter connections with
      both pSTS and FG and could thus provide inputs to these two areas.

PMID- 21095231
TI  - Speech-induced suppression of evoked auditory fields in children who stutter.
AB  - Auditory responses to speech sounds that are self-initiated are suppressed
      compared to responses to the same speech sounds during passive listening. This
      phenomenon is referred to as speech-induced suppression, a potentially important
      feedback-mediated speech-motor control process. In an earlier study, we found
      that both adults who do and do not stutter demonstrated a reduced amplitude of
      the auditory M50 and M100 responses to speech during active production relative
      to passive listening. It is unknown if auditory responses to self-initiated
      speech-motor acts are suppressed in children or if the phenomenon differs between
      children who do and do not stutter. As stuttering is a developmental speech
      disorder, examining speech-induced suppression in children may identify possible
      neural differences underlying stuttering close to its time of onset. We used
      magnetoencephalography to determine the presence of speech-induced suppression in
      children and to characterize the properties of speech-induced suppression in
      children who stutter. We examined the auditory M50 as this was the earliest
      robust response reproducible across our child participants and the most likely to
      reflect a motor-to-auditory relation. Both children who do and do not stutter
      demonstrated speech-induced suppression of the auditory M50. However, children
      who stutter had a delayed auditory M50 peak latency to vowel sounds compared to
      children who do not stutter indicating a possible deficiency in their ability to
      efficiently integrate auditory speech information for the purpose of establishing
      neural representations of speech sounds.

PMID- 21095232
TI  - Phylogenetics and phylogeography of the monocot genus Baldellia (Alismataceae):
      Mediterranean refugia, suture zones and implications for conservation.
AB  - Aquatic plants, and especially the emblematic genus Baldellia (Alismataceae), are
      among the most threatened organisms, due to unprecedented human-driven habitat
      destructions. Therefore protection plans are crucially needed and call for
      thoroughly documenting the genetic diversity and clarifying the taxonomy of this
      endangered genus. Our sampling included 282 individuals from 42 natural
      populations and covered the whole geographical range of the genus, across Europe
      and the Mediterranean. We combined sequencing of nuclear internal transcribed
      spacer (ITS) and chloroplastic trnL-ndhF regions with amplified fragment length
      polymorphism (AFLP) genotyping to investigate the Alismataceae phylogeny, and
      produce a phylogeography of Baldellia. Our phylogeny strongly supported the
      monophyly of Baldellia and placed it as the sister clade to Luronium and Alisma,
      therefore excluding, as previously supposed, a close genetic relatedness to the
      predominantly neotropical genus Echinodorus. The phylogeography of Baldellia
      outlined patterns consistent with a hypothesis considering glacial refugia
      located in the Iberian Peninsula and the Italy/Balkan region from which two
      distinct genetic lineages re-colonized Europe. These two lineages corresponded
      respectively to Baldellia ranunculoides (Italy/Balkan derived populations) and
      Baldellia repens (populations recovered from the Iberian Peninsula refuge),
      therefore supporting differences outlined between the two taxa in previous
      ecological and morphological studies. These results allowed clarifying taxonomic
      uncertainties by confirming the genetic distinctness of B. repens according to B.
      ranunculoides. A third lineage, Baldellia alpestris, originated and remained
      endemic to the mountainous regions of the Iberian Peninsula. Unexpectedly, B.
      repens populations collected in northern Africa, appeared to be genetically
      distinct from their European counterparts, this calls for further investigation
      to fully address their genetic and conservation status. Finally, we detected a
      large hybridization zone in northwestern Europe between B. repens and B.
      ranunculoides. These results were discussed in light of conservation approaches
      for Baldellia populations.

PMID- 21095233
TI  - Recent vicariant and dispersal events affecting the phylogeny and biogeography of
      East Asian freshwater crab genus Nanhaipotamon (Decapoda: Potamidae).
AB  - The molecular phylogeny and biogeography of the East Asian freshwater crabs of
      the genus Nanhaipotamon (Decapoda: Brachyura: Potamidae) were studied, using two
      mitochondrial (16S rRNA and cytochrome oxidase I) and one nuclear (28S rRNA)
      markers, and correlated with various vicariant and dispersal events which have
      occurred in this region. The results showed Nanhaipotamon to be a monophyletic
      taxon with four clades which correspond to the topography of the coastal region
      of southeastern China and Taiwan Island. Mountains appear to play an important
      role in the distribution. The genus occurs only from east of the Wuyishan Range
      (Zhejiang and Fujian) and south of the Nanling Range (Guangdong) in southern
      China, and is also present west of the Central Range in Taiwan. The molecular and
      geological data suggest that Nanhaipotamon originated in an area between the
      Wuyishan and Nanling Ranges. In this area, the main and earliest cladogenesis
      occurred at ~4.8 million years ago (mya), with speciation probably taking place
      at around 4mya. The molecular evidence strongly supports the recent invasion of
      the genus into Taiwan Island from northeastern Fujian, via the paleo-Minjiang
      River on the landbridge of Taiwan Strait. The presence of the genus in Dongyin
      Island, however, is through invasion from southeastern Zhejiang, during the
      Pleistocene glaciation period. Nanhaipotamon reached Taiwan and Dongyin Island at
      ~1.0 and 0.4 mya, respectively. A small population of Nanhaipotamon formosanum
      from Penghu Islands (Pescadores) in the central Taiwan Strait has a slightly
      different genetic constitution and suggests it is a relict of past Pleistocene
      glaciations.

PMID- 21095234
TI  - Molecular systematics of the African snake family Lamprophiidae Fitzinger, 1843
      (Serpentes: Elapoidea), with particular focus on the genera Lamprophis Fitzinger
      1843 and Mehelya Csiki 1903.
AB  - The snake family Lamprophiidae Fitzinger (Serpentes: Elapoidea) is a putatively
      Late Eocene radiation of nocturnal snakes endemic to the African continent. It
      incorporates many of the most characteristic and prolific of Africa's non
      venomous snake species, including the widespread type genus Lamprophis Fitzinger,
      1843 (house snakes). We used approximately 2500 bases of mitochondrial and
      nuclear DNA sequence data from 28 (41%) of the approximately 68 recognised
      lamprophiid species in nine of the eleven genera to investigate phylogenetic
      structure in the family and to inform taxonomy at the generic level. Cytochrome
      b, ND4 and tRNA gene sequences (mitochondrial) and c-mos sequences (nuclear) were
      analysed using Maximum Likelihood, Bayesian Inference and Maximum Parsimony
      methods. The genus Mehelya Csiki, 1903 was paraphyletic with respect to
      Gonionotophis Boulenger, 1893. To address this, the concept of Gonionotophis is
      expanded to include all current Mehelya species. The genus Lamprophis emerged
      polyphyletic: the enigmatic Lamprophis swazicus was sister to Hormonotus modestus
      from West Africa, and not closely related to its nominal congeners. It is moved
      to a new monotypic genus (Inyoka gen. nov.). The remaining Lamprophis species
      occur in three early-diverging lineages. (1) Lamprophis virgatus and the widely
      distributed Lamprophis fuliginosus species complex (which also includes
      Lamprophis lineatus and Lamprophis olivaceus) formed a clade for which the
      generic name Boaedon Dumeril, Bibron & Dumeril, 1854 is resurrected. (2) The
      water snakes (Lycodonomorphus) were nested within Lamprophis (sensu lato), sister
      to Lamprophis inornatus. We transfer this species to the genus Lycodonomorphus
      Fitzinger, 1843. (3) We restrict Lamprophis (sensu strictissimo) to a small clade
      of four species endemic to southern Africa: the type species of Lamprophis
      Fitzinger, 1843 (Lamprophis aurora) plus Lamprophis fiskii, Lamprophis fuscus and
      Lamprophis guttatus.

PMID- 21095235
TI  - Pattern and process of diversification in an ecologically diverse epifaunal
      bivalve group Pterioidea (Pteriomorphia, Bivalvia).
AB  - The pterioid bivalves (superfamily Pterioidea) are epifaunal filter feeders that
      attach to various substrata, including rocks, corals, gorgonians, and sponges. An
      intriguing question is how different substratum types have affected the
      diversification of pterioid bivalves. To elucidate the evolutionary pathway of
      Pterioidea, we conducted a phylogenetic analysis of 49 individuals belonging to
      18 pterioid and 5 outgroup species using 18S and 28S ribosomal RNA genes. The
      results supported the monophyly of superfamily Pterioidea and recovered three
      major clades within Pterioidea: Malleus, Pteria and Electroma (Pterelectroma)
      zebra and the rest. This result contradicts the current circumscription of the
      pterioid families, Pteriidae, Malleidae, and Isognomonidae, and suggests that
      hinge morphology, which has long been used as a diagnostic character, does not
      reflect phylogenetic relationships. The monophyly of most genera, however, was
      confirmed. Mapping substrata types on the phylogenetic tree indicated that the
      ancestors of pterioid bivalves were epifaunal on rocks, and that epizoic life on
      sessile cnidarians had a single origin. Although we could not ascertain whether
      endozoic life in sponges evolved once or twice, our results suggest that
      colonization of biotic substrata resulted in diversification and morphological
      and ecological adaptation to epi-/endozoic life. We estimated that the genus
      Pteria has diversified since the late Cretaceous in response to gorgonian
      diversification. These results emphasize the importance of substratum shifts in
      speciation and diversification of pterioid bivalves.

PMID- 21095236
TI  - Galatheoidea are not monophyletic - molecular and morphological phylogeny of the
      squat lobsters (Decapoda: Anomura) with recognition of a new superfamily.
AB  - The monophyletic status of the squat lobster superfamily Galatheoidea has come
      under increasing doubt by studies using evidence as diverse as larval and adult
      somatic morphology, sperm ultrastructure, and molecular data. Here we synthesize
      phylogenetic data from these diverse strands, with the addition of new molecular
      and morphological data to examine the phylogeny of the squat lobsters and assess
      the status of the Galatheoidea. A total of 64 species from 16 of the 17 currently
      recognised anomuran families are included. Results support previous work pointing
      towards polyphyly in the superfamily Galatheoidea and Paguroidea, specifically,
      suggesting independent origins of the Galatheidae+Porcellanidae and the
      Chirostylidae+Kiwaidae. Morphological characters are selected that support clades
      resolved in the combined analysis and the taxonomic status of Galatheoidea sensu
      lato is revised. Results indicate that Chirostylidae are more closely related to
      an assemblage including Aegloidea, Lomisoidea and Paguroidea than to the
      remaining Galatheoidea and are referred to the superfamily Chirostyloidea to
      include the Chirostylidae and Kiwaidae. A considerable amount of research
      highlighting morphological differences supporting this split is discussed. The
      Galatheoidea sensu stricto is restricted to the families Galatheidae and
      Porcellanidae, and diagnoses for both Chirostyloidea and Galatheoidea are
      provided. Present results highlight the need for a detailed revision of a number
      of taxa, challenge some currently used morphological synapomorphies, and
      emphasise the need for integrated studies with wide taxon sampling and multiple
      data sources to resolve complex phylogenetic questions.

PMID- 21095237
TI  - PGE1 and PGE2 modify platelet function through different prostanoid receptors.
AB  - There is evidence that the overall effects of prostaglandin E(2) (PGE(2)) on
      human platelet function are the consequence of a balance between promotory
      effects of PGE(2) acting at the EP3 receptor and inhibitory effects acting at the
      EP4 receptor, with no role for the IP receptor. Another prostaglandin that has
      been reported to affect platelet function is prostaglandin E(1) (PGE(1)), however
      the receptors that mediate its actions on platelet function have not been fully
      defined. Here we have used measurements of platelet aggregation and P-selectin
      expression induced by the thromboxane A(2) mimetic U46619 to compare the effects
      of PGE(1) and PGE(2) on platelet function. Their effects on vasodilator
      stimulated phosphoprotein (VASP) phosphorylation, as a marker of cAMP, were also
      determined. We also investigated the ability of the selective prostanoid receptor
      antagonists CAY10441 (IP antagonist), DG-041 (EP3 antagonist) and ONO-AE3-208
      (EP4 antagonist) to modify the effects of the prostaglandins on platelet
      function. The results obtained confirm that PGE(2) interacts with EP3 and EP4
      receptors, but not IP receptors. In contrast PGE(1) interacts with EP3 and IP
      receptors, but not EP4 receptors. In both cases the overall effects on platelet
      function reflect the balance between promotory and inhibitory effects at
      receptors that have opposite effects on adenylate cyclase.

PMID- 21095238
TI  - Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle
      cells by mediating the transport of angiotensin II type 1 receptor under hypoxia.
AB  - Previous studies have demonstrated that Rab1 is involved in the export of
      angiotensin II (Ang II) type 1 receptor (AT1R) to the cell surface in endothelial
      cells and cardiomyocytes. The aim of this study was to evaluate whether the
      modification of Rab1-mediated endoplasmic reticulum (ER) to the Golgi body
      transport alters the cell surface expression and function of endogenous AT1R and
      AT1R-mediated phenotypic modulation in primary cultures of pulmonary artery
      smooth muscle cells (PASMCs). Lentiviral expression of wild-type Rab1 (Rab1WT)
      significantly increased cell surface expression of endogenous AT1R. However, Rab1
      siRNA had the opposite effect, and attenuated downregulation of the expression of
      PASMCs phenotype markers, alpha smooth muscle actin (alpha-SMA) and vimentin
      (VIM) in rat pulmonary artery smooth muscle cells (RPASMCs) during hypoxia.
      Analysis of the subcellular localization of AT1R revealed that Rab1 regulated
      AT1R transport from the ER to the Golgi in PASMCs. Consistent with their effects
      on AT1R export, Rab1 modified the AT1R-mediated cell growth and the
      phosphorylation of signal transducing activator of transcription 3 (STAT3) during
      hypoxia. We found that hypoxia promoted Rab1 expression and strongly correlated
      with the repressed expression of PASMC phenotype markers in RPASMCs. These data
      strongly indicate that Rab1 modulates PASMCs function by manipulating AT1R
      traffic from the ER to the Golgi and provide the first evidence implicating ER-to
      Golgi transport as a regulatory step for the control of RPASMCs growth.

PMID- 21095240
TI  - Magnetic fields promote a pro-survival non-capacitative Ca2+ entry via
      phospholipase C signaling.
AB  - The ability of magnetic fields (MFs) to promote/increase Ca(2+) influx into cells
      is widely recognized, but the underlying mechanisms remain obscure. Here we
      analyze how static MFs of 6 mT modulates thapsigargin-induced Ca(2+) movements in
      non-excitable U937 monocytes, and how this relates to the anti-apoptotic effect
      of MFs. Magnetic fields do not affect thapsigargin-induced Ca(2+) mobilization
      from endoplasmic reticulum, but significantly increase the resulting Ca(2+)
      influx; this increase requires intracellular signal transduction actors including
      G protein, phospholipase C, diacylglycerol lipase and nitric oxide synthase, and
      behaves as a non-capacitative Ca(2+) entry (NCCE), a type of influx with an
      inherent signaling function, rather than a capacitative Ca(2+) entry (CCE). All
      treatments abrogating the extra Ca(2+) influx also abrogate the anti-apoptotic
      effect of MFs, demonstrating that MF-induced NCCE elicits an anti-apoptotic
      survival pathway.

PMID- 21095239
TI  - Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-activated
      c-Jun N-terminal protein kinase 1 contributes to survival of erythropoietin
      dependent cells.
AB  - The glycoprotein erythropoietin (Epo) is a hematopoietic cytokine necessary for
      the survival of erythrocytes from immature erythroid cells. The mitogen-activated
      c-Jun N-terminal kinase 1 (JNK1) plays an important role in the proliferation and
      survival of erythroid cells in response to Epo. However, the precise mechanism of
      JNK1 activation promoting erythroid cell survival is incompletely understood.
      Here, we reported that JNK1 is required for Epo-mediated cell survival through
      phosphorylation and inactivation of the pro-apoptotic, Bcl-2 homology domain 3
      (BH3)-only Bcl-associated death protein (Bad). Upon Epo withdrawal, HCD57 cells,
      a murine Epo-dependent cell line, displayed increased apoptotic cell death that
      was associated with decreased JNK1 activity. Epo withdrawal-induced apoptosis was
      promoted by inhibition of JNK1 activity but suppressed by expression of a
      constitutively active JNK1. Furthermore, Epo-activated JNK1 phosphorylated Bad at
      threonine 201, thereby inhibiting the association of Bad with the anti-apoptotic
      molecule B-cell lymphoma-extra large (Bcl-X(L)). Replacement of threonine 201 by
      alanine in Bad promoted Epo withdrawal-induced apoptosis. Thus, our results
      provide a molecular mechanism by which JNK1 contributes to the survival of
      erythroid cells.

PMID- 21095242
TI  - Systemic vascular diseases in the antiphospholipid syndrome. What is the best
      diagnostic choice?
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease which is characterized
      by arterial and venous thromboses, fetal loss, and the presence of
      antiphospholipid antibodies in the serum (aPL). It is characterized by
      accelerated atherosclerosis and that together with an increased tendency towards
      thrombosis leading to the occurrence of various vascular events. Timely diagnosis
      of vascular changes, preferably in subclinical phase, is required due both to
      their severity and to the high mortality rate. Detection of arterial and venous
      changes nowadays is performed through diversity of invasive and non invasive
      diagnostic methods. 64-multi slice computed tomographic angiography (64-MSCT)
      seems to be the most precise method with low exposure time, giving the
      opportunity for clinicians to early diagnose and timely treat APS patients.

PMID- 21095241
TI  - DNA damage phenotype and prostate cancer risk.
AB  - The capacity of an individual to process DNA damage is considered a crucial
      factor in carcinogenesis. The comet assay is a phenotypic measure of the combined
      effects of sensitivity to a mutagen exposure and repair capacity. In this paper,
      we evaluate the association of the DNA repair kinetics, as measured by the comet
      assay, with prostate cancer risk. In a pilot study of 55 men with prostate
      cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we
      investigated the association of DNA damage with prostate cancer risk at early (0
      15 min) and later (15-45 min) stages following gamma-radiation exposure. Although
      residual damage within 45 min was the same for all groups (65% of DNA in comet
      tail disappeared), prostate cancer cases had a slower first phase (38% vs. 41%)
      and faster second phase (27% vs. 22%) of the repair response compared to
      controls. When subjects were categorized into quartiles, according to efficiency
      of repairing DNA damage, high repair-efficiency within the first 15 min after
      exposure was not associated with prostate cancer risk while higher at the 15-45
      min period was associated with increased risk (OR for highest-to-lowest
      quartiles=3.24, 95% CI=0.98-10.66, p-trend=0.04). Despite limited sample size,
      our data suggest that DNA repair kinetics marginally differ between prostate
      cancer cases and controls. This small difference could be associated with
      differential responses to DNA damage among susceptible individuals.

PMID- 21095243
TI  - Dynamic mechanical analysis and biomineralization of hyaluronan-polyethylene
      copolymers for potential use in osteochondral defect repair.
AB  - Treatment options for damaged articular cartilage are limited due to its lack of
      vasculature and its unique viscoelastic properties. This study was the first to
      fabricate a hyaluronan (HA)-polyethylene copolymer for potential use in the
      replacement of articular cartilage and repair of osteochondral defects.
      Amphiphilic graft copolymers consisting of HA and high-density polyethylene (HA
      co-HDPE) were fabricated with 10, 28 and 50 wt.% HA. Dynamic mechanical analysis
      was used to assess the effect of varying constituent weight ratios on the
      viscoelastic properties of HA-co-HDPE materials. The storage moduli of HA-co-HDPE
      copolymers ranged from 2.4 to 15.0 MPa at physiological loading frequencies. The
      viscoelastic properties of the HA-co-HDPE materials were significantly affected
      by varying the wt.% of HA and/or crosslinking of the HA constituent. Cytotoxicity
      and the ability of the materials to support mineralization were evaluated in the
      presence of bone marrow stromal cells. HA-co-HDPE materials were non-cytotoxic,
      and calcium and phosphorus were present on the surface of the HA-co-HDPE
      materials 2 weeks after osteogenic differentiation of the bone marrow stromal
      cells. This study is the first to measure the viscoelastic properties and
      osseocompatibility of HA-co-HDPE for potential use in orthopedic applications.

PMID- 21095244
TI  - Electrospun gelatin nanofibers: optimization of genipin cross-linking to preserve
      fiber morphology after exposure to water.
AB  - The development of suitable biomimetic three-dimensional scaffolds is a
      fundamental requirement of tissue engineering. This paper presents the first
      successful attempt to obtain electrospun gelatin nanofibers cross-linked with a
      low toxicity agent, genipin, and able to retain the original nanofiber morphology
      after water exposure. The optimized procedure involves an electrospinning
      solution containing 30 wt.% gelatin in 60/40 acetic acid/water (v/v) and a small
      amount of genipin, followed by further cross-linking of the as-electrospun mats
      in 5% genipin solution for 7 days, rinsing in phosphate-buffered saline and then
      air drying at 37 degrees C. The results of scanning electron microscopy
      investigations indicated that the cross-linked nanofibers were defect free and
      very regular and they also maintained the original morphology after exposure to
      water. Genipin addition to the electrospinning solution dramatically reduced the
      extensibility of the as-electrospun mats, which displayed further remarkable
      improvements in elastic modulus and stress at break after successive cross
      linking up to values of about 990 and 21 MPa, respectively. The results of the
      preliminary in vitro tests carried out using vascular wall mesenchymal stem cells
      indicated good cell viability and adhesion to the gelatin scaffolds.

PMID- 21095245
TI  - The effects of water and microstructure on the mechanical properties of bighorn
      sheep (Ovis canadensis) horn keratin.
AB  - The function of the bighorn sheep horn prompted quantification of the various
      parametric effects important to the microstructure and mechanical property
      relationships of this horn. These parameters included analysis of the stress
      state dependence with the horn keratin tested under tension and compression, the
      anisotropy of the material structure and mechanical behavior, the spatial
      location along the horn, and the wet-dry horn behavior. The mechanical properties
      of interest were the elastic moduli, yield strength, ultimate strength, failure
      strain and hardness. The results showed that water has a more significant effect
      on the mechanical behavior of ram horn more than the anisotropy, location along
      the horn and the type of loading state. All of these parametric effects showed
      that the horn microstructure and mechanical properties were similar to those of
      long-fiber composites. In the ambient dry condition (10 wt.% water), the
      longitudinal elastic modulus, yield strength and failure strain were measured to
      be 4.0 G Pa, 62 MPa and 4%, respectively, and the transverse elastic modulus,
      yield strength and failure strain were 2.9 GPa, 37 MPa and 2%, respectively. In
      the wet condition (35 wt.% water), horn behaves more like an isotropic material;
      the elastic modulus, yield strength and failure strain were determined to be 0.6G
      Pa, 10 MPa and 60%, respectively.

PMID- 21095246
TI  - Preparation of well-defined poly(ether-ester) macromers: photogelation and
      biodegradability.
AB  - Two series of poly(ether-ester)-based bis-functional macromers terminated with
      acrylate groups and a well-defined number of ester bonds were synthesized. One
      series had a chain of 1, 3 or 5 ester bonds at both ends of the central
      poly(ethylene glycol) block (molecular weight, about 1000), while the other had
      an alternating structure of oligo(ethylene glycol) each of them linked to two
      ester bonds, in which 6 or 10 ester bonds were incorporated equally in the
      macromer molecules and the total molecular weight was adjusted by about 1000.
      Irradiation of all poly(ether-ester) macromers mixed with camphorquinone resulted
      in the formation of gels. Gel yield increased and hydrophilic properties of the
      gels produced decreased with irradiation time. The elastic modulus of the gels
      decreased with the number of ester bonds. Upon incubation in a PBS solution (pH
      8.04), all gels were gradually degraded with time. At 3 weeks of incubation, the
      degradation ratio increased linearly with the number of ester bonds per unit of
      molecular weight of the macromers. The order of in vivo degradation rates
      determined from weight loss was similar to that of the in vitro study. Thus,
      these poly(ether-ester) macromers may be useful for biodegradable biomaterials or
      tissue engineering scaffolds.

PMID- 21095247
TI  - Alternative splicing in bone following mechanical loading.
AB  - It is estimated that more than 90% of human genes express multiple mRNA
      transcripts due to alternative splicing. Consequently, the proteins produced by
      different splice variants will likely have different functions and expression
      levels. Several genes with splice variants are known in bone, with functions that
      affect osteoblast function and bone formation. The primary goal of this study was
      to evaluate the extent of alternative splicing in a bone subjected to mechanical
      loading and subsequent bone formation. We used the rat forelimb loading model, in
      which the right forelimb was loaded axially for 3 min, while the left forearm
      served as a non-loaded control. Animals were subjected to loading sessions every
      day, with 24 h between sessions. Ulnae were sampled at 11 time points, from 4 h
      to 32days after beginning loading. RNA was isolated and mRNA abundance was
      measured at each time point using Affymetrix exon arrays (GeneChip(r) Rat Exon
      1.0 ST Arrays). An ANOVA model was used to identify potential alternatively
      spliced genes across the time course, and five alternatively spliced genes were
      validated with qPCR: Akap12, Fn1, Pcolce, Sfrp4, and Tpm1. The number of
      alternatively spliced genes varied with time, ranging from a low of 68 at 12h to
      a high of 992 at 16d. We identified genes across the time course that encoded
      proteins with known functions in bone formation, including collagens, matrix
      proteins, and components of the Wnt/beta-catenin and TGF-beta signaling pathways.
      We also identified alternatively spliced genes encoding cytokines, ion channels,
      muscle-related genes, and solute carriers that do not have a known function in
      bone formation and represent potentially novel findings. In addition, a
      functional characterization was performed to categorize the global functions of
      the alternatively spliced genes in our data set. In conclusion, mechanical
      loading induces alternative splicing in bone, which may play an important role in
      the response of bone to mechanical loading.

PMID- 21095249
TI  - The Match: five years later.

PMID- 21095248
TI  - Autophagy and misfolded proteins in neurodegeneration.
AB  - The accumulation of misfolded proteins in insoluble aggregates within the
      neuronal cytoplasm is one of the common pathological hallmarks of most adult
      onset human neurodegenerative diseases. The clearance of these misfolded proteins
      may represent a promising therapeutic strategy in these diseases. The two main
      routes for intracellular protein degradation are the ubiquitin-proteasome and the
      autophagy-lysosome pathways. In this review, we will focus on the autophagic
      pathway, by providing some examples of how impairment at different steps in this
      degradation pathway is related to different neurodegenerative diseases. We will
      also consider that upregulating autophagy may be useful in the treatment of some
      of these diseases. Finally, we discuss how antioxidants, which have been
      considered to be beneficial in neurodegenerative diseases, can block autophagy,
      thus potentially compromising their therapeutic potential.

PMID- 21095250
TI  - In vitro analysis of the factors contributing to the antiviral state induced by a
      plasmid encoding the viral haemorrhagic septicaemia virus glycoprotein G in
      transfected trout cells.
AB  - We have found out that transfection of the RTG-2 cell line with the viral
      haemorrhagic septicaemia virus (VHSV) glycoprotein G (G(VHSV))-coding plasmid
      induces an anti-VHSV state, similar to that induced by poly I:C. Taking the
      advantage of the constitutive expression of toll-like receptor 9 gene (tlr9) in
      RTG-2 cells, we have investigated whether this antiviral state was induced by the
      cytosine-phosphodiester-guanine (CpG) motifs present in the plasmid DNA, by the
      endogenous expression of G(VHSV) protein or by both elements. For that, we have
      analysed the expression profile of the rainbow trout tlr9 and several genes
      related to TLR9-mediated immune response in the absence or presence of a
      lysosomotropic drug that specifically blocks TLR9-CpG DNA interaction. The
      results suggested that the high levels of cell protection conferred by a plasmid
      encoding G(VHSV) gene are due to G(VHSV) rather than to the CpG motifs within
      plasmid DNA. Therefore, plasmid DNA might not play a key role in the immune
      response elicited by DNA vaccines or perhaps other receptors instead TLR9 could
      be implicated in CpG motifs recognition and signalling. In addition, since RTG-2
      cells express tlr9 gene, this cell line could be a good tool for screening TLR9
      agonists, such as the immunomodulatory oligonucleotides (IMOs), as fish DNA
      vaccine adjuvants.

PMID- 21095252
TI  - A novel Salmonella Typhi-based immunotherapy promotes tumor killing via an
      antitumor Th1-type cellular immune response and neutrophil activation in a mouse
      model of breast cancer.
AB  - We investigated the use of a live, attenuated Salmonella enterica serovar Typhi
      vaccine strain as an antitumor immunotherapy. Mice bearing a subcutaneous tumor
      (LM3 mammary adenocarcinoma) were immunized on three occasions with S. Typhi
      strain CVD 915 by injection into the tumor, the peritumoral tissue and the
      draining lymph node areas; this procedure was termed Salmonella multiple
      treatment (Salmonella MT). Tumor-bearing mice subjected to the Salmonella MT
      exhibited reduced tumor growth, prolonged survival and reduced incidence of lung
      metastases, compared to untreated mice. We examined the mechanisms mediating this
      effect and found that Salmonella MT promoted an antitumor Th1-type response
      characterized by increased frequencies of IFN-gamma-secreting CD4(+) T and CD8(+)
      T cells with reduction of regulatory T cells in tumor draining lymph nodes. The
      main cells infiltrating bacteria-treated tumors were activated neutrophils, which
      can exert an antitumor effect through the secretion of TNF-alpha. These results
      demonstrate for the first time the efficacy of an attenuated S. Typhi vaccine
      strain as a cancer immunotherapeutic agent. By potentiating the host antitumor
      immune response, this approach could be a powerful adjunct tool for cancer
      therapy.

PMID- 21095251
TI  - LT-IIc, a new member of the type II heat-labile enterotoxin family, exhibits
      potent immunomodulatory properties that are different from those induced by LT
      IIa or LT-IIb.
AB  - A plethora of human pathogens invade and/or colonize mucosal surfaces.
      Elaboration of strong, protective immune responses against those pathogens by
      mucosal vaccination, however, is hampered by endogenous regulatory systems in the
      mucosae that dampen responses to foreign antigens (Ags). To overcome those
      natural barriers, mucosal adjuvants must be employed. Using a mouse mucosal
      immunization model and AgI/II, a weak immunogen from Streptococcus mutans, LT
      IIc, a new member of the type II subgroup of the heat-labile enterotoxin family,
      was shown to have potent mucosal adjuvant properties. In comparison to mice
      intranasally immunized only with AgI/II, co-administration of AgI/II with LT-IIc
      enhanced production of Ag-specific IgA antibodies in the saliva and vaginal
      fluids and Ag-specific IgA and IgG in the serum. Secretion of IL-2, IL-6, IL-17,
      IFN-gamma, and TNF-alpha was enhanced in cultures of AgI/II-stimulated splenic
      cells isolated from mice that had received LT-IIc as a mucosal adjuvant. In
      contrast, secretion of IL-10 was suppressed in those cells. This pattern of
      cytokine secretion suggested that LT-IIc stimulates both Th1 and Th2 immune
      responses. In contrast to LT-IIa and LT-IIb, the original members of the type II
      subgroup that also are mucosal adjuvants, LT-IIc dramatically enhanced secretion
      of IL-1alpha and IL-1beta in peritoneal macrophages that had been co-cultured
      with LPS. Furthermore, the B pentameric subunit of LT-IIc augmented uptake of Ag
      by bone marrow-derived dendritic cells to levels that exceeded those attained by
      use of LPS or by the B pentamers of LT-IIa or LT-IIb. These data confirmed that
      LT-IIc is a strong mucosal adjuvant with immunomodulatory properties that are
      distinguishable from those of LT-IIa and LT-IIb and which has immunomodulatory
      properties that may be exploitable in vaccine development.

PMID- 21095253
TI  - Comparison of influenza vaccine effectiveness using different methods of case
      detection: clinician-ordered rapid antigen tests vs. active surveillance and
      testing with real-time reverse-transcriptase polymerase chain reaction (rRT-PCR).
AB  - Annual evaluation of influenza vaccine effectiveness (VE) is needed to assess
      ongoing impact of immunization efforts in the setting of antigenic drift and
      periodic vaccine reformulation. Optimal methodology for determining VE remains
      unclear. We compared influenza VE generated from prospective enrollment and rRT
      PCR testing (active surveillance group) with VE based on clinician-ordered
      diagnostic tests (clinical testing group) in a defined population over four
      seasons. VE was calculated as (1 - adjusted OR) for vaccination in cases vs. test
      negative controls. VE based on clinical testing underestimated VE based on active
      surveillance and testing with rRT-PCR by 5-33% depending on season.

PMID- 21095254
TI  - Evaluation of the immune response induced by DNA vaccine cocktail expressing
      complete SAG1 and ROP2 genes against toxoplasmosis.
AB  - Toxoplasma gondii, the pathogen of toxoplasmosis, can infect most mammals and
      birds. The high incidence and severe or lethal damages of toxoplasmosis clearly
      indicate the need for the development of a more effective vaccine. We constructed
      a DNA cocktail, containing plasmids encoding the full-length SAG1 and ROP2 genes
      of T. gondii and evaluated its immune response and protective efficacy in
      comparison with single-gene vaccines and control groups. We immunized BALB/c mice
      intramuscularly three times. DNA cocktail elicited IgG and IFN-gamma, TNF-alpha
      and IL-2 greater than single-gene plasmids and increased survival time against a
      lethal challenge with the highly virulent T. gondii RH strain. The current study
      shows that pc-SAG1+ pc-ROP2 as a cocktail DNA vaccine produces higher Th1 immune
      response than single-gene plasmids and cocktail DNA is effective to prime an
      enhanced and balanced specific immunity.

PMID- 21095255
TI  - Serological response and persistence in schoolchildren with high baseline
      seropositive rate after receiving 2009 pandemic influenza A(H1N1) vaccine.
AB  - The serological response of the current 2009 H1N1 pandemic influenza monovalent
      vaccine in children exhibiting high baseline seropositive rate was evaluated
      though a community-based household study. Seroprotection rate of >90% and
      seroconversion rate of >50% were observed in children one month after receiving
      the pandemic vaccine. Among children with low baseline antibody titer, a
      significant lower seroconversion rate (55%) was observed in children who received
      seasonal trivalent inactivated vaccine (TIV) prior to pandemic vaccine, when
      compared with those receiving the pandemic vaccine only (86%). Persistence of
      antibody against the pandemic influenza virus was observed 6 months after
      vaccination in >80% of children presenting seroprotective antibody levels.

PMID- 21095256
TI  - Evaluation of a DNA vaccine candidate expressing prM-E-NS1 antigens of dengue
      virus serotype 1 with or without granulocyte-macrophage colony-stimulating factor
      (GM-CSF) in immunogenicity and protection.
AB  - Dengue is one of the most important mosquito-borne viral diseases. In past years,
      although considerable effort has been put into the development of a vaccine,
      there is currently no licensed dengue vaccine. In this study, we constructed DNA
      vaccines that carried the prM-E-NS1 genes of dengue virus serotype 1 (DV1) with
      or without the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, an
      attractive DNA vaccine adjuvant. Immunization with the plasmid pCAG-DV1/E/NS1,
      which expresses viral prM-E-NS1, or the bicistronic plasmid pCAG-DV1-GM, which co
      expresses viral prM-E-NS1 and GM-CSF, resulted in long-term IgG response, high
      levels of splenocyte-secreted interferon-gamma and interleukin-2, strong
      cytotoxic T lymphocyte activity and sufficient protection in the DV1-challenged
      mice. This suggested that both humoral and cellular immune responses were induced
      by the immunizations and that they played important roles in protection against
      the DV1 challenge. Interestingly, the magnitude, quality and protective capacity
      of the immune responses induced by immunization with pCAG-DV1/E/NS1 or pCAG-DV1
      GM seemed stronger than those induced by pCAG-DV1/E (expressing viral prM-E
      alone). Taken together, we demonstrated that prM/E plus NS1 would be a suitable
      solution for the development of a DNA vaccine against DV.

PMID- 21095257
TI  - CD4+ and CD8+ T cell- and IL-17-mediated protection against Entamoeba histolytica
      induced by a recombinant vaccine.
AB  - Amebiasis in the murine model can be prevented by vaccination with the Gal/GalNAc
      lectin through a T cell-dependent mechanism. In this work we further decipher the
      mechanism of this protection. Mice vaccinated with the recombinant "LecA"
      fragment of the Gal/GalNAc lectin with alum were capable of transferring
      protection to naive recipients by both CD4+ T cells and surprisingly CD8+ T
      cells. We then examined the cytokine profile of these cells. CD4+ T cells from
      PBMC of LecA-alum vaccinated mice were observed to be a major source of IFN
      gamma, known to be a protective cytokine with this vaccine. In contrast, CD8+ T
      cells produced relatively little IFN-gamma but more IL-17 than the CD4
      compartment. We thus examined the role of IL-17 in vaccine mediated protection
      and found through neutralization experiments that this cytokine contributed to
      LecA-alum vaccine protection. In addition we examined whether these cells
      exhibited direct amebicidal activity in vitro and found that both populations had
      amebicidal activity at high concentrations (1000:1) but CD8+ T cells appeared
      more potent, capable of cytotoxicity at a 100:1 ratio. In conclusion, both CD4
      and CD8 T cells exert protection with this amebiasis vaccine. The mechanism of
      CD8 T cell-mediated protection may include direct amebicidal activity and/or IL
      17 production. Both IL-17 and IFN-gamma are useful surrogates for immune
      protection.

PMID- 21095259
TI  - Oral administration of heat-killed Lactobacillus pentosus strain b240 augments
      protection against influenza virus infection in mice.
AB  - Host-defense mechanisms against influenza virus (IFV) infection involve both
      innate and acquired immunities. Among other components, secretory immunoglobulin
      A (SIgA) in the airway mucosa plays a particularly pivotal role in preventing IFV
      infection. Among 150 strains of lactic acid bacteria, Lactobacillus pentosus
      strain b240 (b240) has the highest IgA-inducing potency in mouse Peyer's patch
      cells. We previously reported a practical new finding that oral ingestion of
      nonviable heat-killed b240 elevates salivary IgA secretion in humans. The present
      study aimed to determine if nonviable b240 can prevent IFV infection in mice. In
      a BALB/c mouse model infected with lethal levels of IFV A/PR8/34 (H1N1), oral
      administration of b240 for 3 weeks by gavage prior to IFV infection significantly
      prolonged the survival period. For IFV infection at nonlethal levels, the
      infectious titers of IFV in the lungs 7 days after infection were significantly
      reduced after similar b240 administration. Both anti-IFV IgA and immunoglobulin G
      titers in bronchoalveolar lavage fluid and plasma on day 7 were significantly
      higher in the b240-treated group than the control group. The augmentation of the
      anti-IFV immune response by b240 application was preliminarily confirmed by the
      elevated production of IFV-driven T-cell factors during mixed lymphocyte
      reactions with b240-primed splenocytes. These results suggest that oral nonviable
      heat-killed b240 intake can facilitate protection against IFV infection.

PMID- 21095258
TI  - Towards an immunosense vaccine to prevent toxoplasmosis: protective Toxoplasma
      gondii epitopes restricted by HLA-A*0201.
AB  - The ideal vaccine to protect against toxoplasmosis in humans would include
      antigens that elicit a protective T helper cell type 1 immune response, and
      generate long-lived IFN-gamma-producing CD8(+) T cells. Herein, we utilized a
      predictive algorithm to identify candidate HLA-A02 supertype epitopes from
      Toxoplasma gondii proteins. Thirteen peptides elicited production of IFN-gamma
      from PBMC of HLA-A02 supertype persons seropositive for T. gondii infection but
      not from seronegative controls. These peptides displayed high-affinity binding to
      HLA-A02 proteins. Immunization of HLA-A*0201 transgenic mice with these pooled
      peptides, with a universal CD4(+) epitope peptide called PADRE, formulated with
      adjuvant GLA-SE, induced CD8(+) T cell IFN-gamma production and protected against
      parasite challenge. Peptides identified in this study provide candidates for
      inclusion in immunosense epitope-based vaccines.

PMID- 21095260
TI  - Heparin changes the conformation of high-mobility group protein 1 and decreases
      its affinity toward receptor for advanced glycation endproducts in vitro.
AB  - High-mobility group protein 1 (HMGB1) has been identified as a late-acting
      mediator of inflammation. The receptor for advanced glycation end products (RAGE)
      is the main receptor and mediates the cytokine activity of HMGB1. Since HMGB1
      also exhibits heparin-binding activity, we investigated whether heparin
      interferes with HMGB1/RAGE interaction and prevents the cytokine activity. We
      used fluorescence spectrometry, circular dichroism spectrometry and SPR biosensor
      technique to evaluate the effect. After treatment of HMGB1 with different
      concentrations of heparin (0, 50, 100 and 1000 U/L), the fluorescence peak values
      of HMGB1 increased and the emission wavelength showed red shifts; further, the
      secondary structure of HMGB1 showed a marked change in that the content of beta
      pleated sheet reduced while that of alpha-helix increased. The equilibrium
      dissociation constants (K(D)) were determined by SPR technique; K(D)=4.5 * 10(
      9)mol/L for heparin and HMGB1 and K(D)=9.77 * 10(-8)mol/L for HMGB1 and RAGE,
      respectively. Heparin and RAGE had no interaction. The amount of HMGB1 and RAGE
      bound forms reduced after treatment with heparin. ELISA revealed that addition of
      heparin inhibited the TNF-alpha and IL-6 released by macrophages RAW264.7 and
      HUVEC; 10 U/L and 50 U/L of heparin showed the most marked inhibitory effect in
      RAW264.7 cells and in HUVEC, respectively. In conclusion, heparin can combine
      with HMGB1 and affect the affinity of HMGB1/RAGE by changing the conformation of
      HMGB1. And this effect was independent of heparin concentration, so that a low
      dose of heparin was sufficient to achieve the best anti-inflammatory effect in
      our test.

PMID- 21095261
TI  - Red blood cell storage duration and mortality in patients undergoing percutaneous
      coronary intervention (Am Heart J 2010;159:876-81).

PMID- 21095263
TI  - Study of Heart and Renal Protection (SHARP): randomized trial to assess the
      effects of lowering low-density lipoprotein cholesterol among 9,438 patients with
      chronic kidney disease.
AB  - BACKGROUND: Lowering low-density lipoprotein (LDL) cholesterol with statin
      therapy has been shown to reduce the incidence of atherosclerotic events in many
      types of patient, but it remains uncertain whether it is of net benefit among
      people with chronic kidney disease (CKD). METHODS: Patients with advanced CKD
      (blood creatinine >= 1.7 mg/dL [>= 150 MUmol/L] in men or >= 1.5 mg/dL [ >= 130
      MUmol/L] in women) with no known history of myocardial infarction or coronary
      revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus
      simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily
      (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin
      20 mg daily vs placebo). The key outcome will be major atherosclerotic events,
      defined as the combination of myocardial infarction, coronary death, ischemic
      stroke, or any revascularization procedure. RESULTS: A total of 9,438 CKD
      patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years,
      two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular
      disease. Compared with either placebo or simvastatin alone, allocation to
      ezetimibe plus simvastatin was not associated with any excess of myopathy,
      hepatic toxicity, or biliary complications during the first year of follow-up.
      Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily
      yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year
      and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until
      August 2010, when all patients will have been followed for at least 4 years.
      CONCLUSIONS: SHARP should provide evidence about the efficacy and safety of
      lowering LDL cholesterol with the combination of ezetimibe and simvastatin among
      a wide range of patients with CKD.

PMID- 21095264
TI  - Design and rationale of the Reduction of Infarct Expansion and Ventricular
      Remodeling with Erythropoietin after Large Myocardial Infarction (REVEAL) trial.
AB  - BACKGROUND: Acute myocardial infarction (MI) remains a leading cause of death
      despite advances in pharmacologic and percutaneous therapies. Animal models of
      ischemia/reperfusion have demonstrated that single-dose erythropoietin may reduce
      infarct size, decrease apoptosis, and increase neovascularization, possibly
      through mobilization of endothelial progenitor cells. STUDY DESIGN: REVEAL is a
      randomized, double-blind, placebo-controlled, multicenter trial evaluating the
      effects of epoetin alpha on infarct size and left ventricular remodeling in
      patients with large MIs. The trial comprises a dose-escalation safety phase and a
      single-dose efficacy phase using the highest acceptable epoetin alpha dose up to
      60,000 IU. Up to 250 ST-segment elevation myocardial infarction patients
      undergoing primary or rescue percutaneous coronary intervention will be
      randomized to intravenous epoetin alpha or placebo within 4 hours of successful
      reperfusion. The primary study end point is infarct size expressed as a
      percentage of left ventricular mass, as measured by cardiac magnetic resonance
      imaging 2 to 6 days post study medication administration. Secondary end points
      will assess changes in endothelial progenitor cell numbers and changes in indices
      of ventricular remodeling. CONCLUSION: The REVEAL trial will evaluate the safety
      and efficacy of the highest tolerated single dose of epoetin alpha in patients
      who have undergone successful rescue or primary percutaneous coronary
      intervention for acute ST-segment elevation myocardial infarction.

PMID- 21095265
TI  - Randomized comparison of 6- versus 24-month clopidogrel therapy after balancing
      anti-intimal hyperplasia stent potency in all-comer patients undergoing
      percutaneous coronary intervention Design and rationale for the PROlonging Dual
      antiplatelet treatment after Grading stent-induced Intimal hyperplasia study
      (PRODIGY).
AB  - BACKGROUND: The optimal duration of clopidogrel therapy after coronary stenting
      is debated because of the scarcity of randomized controlled trials and
      inconsistencies arising from registry data. Although prolonged clopidogrel
      therapy after bare metal stenting is regarded as an effective secondary
      prevention measure, the safety profile of drug-eluting stents itself has been
      questioned in patients not receiving >= 12 months of dual-antiplatelet therapy.
      HYPOTHESIS: Twenty-four months of clopidogrel therapy after coronary stenting
      reduces the composite of death, myocardial infarction, or stroke compared with 6
      months of treatment. STUDY DESIGN: PRODIGY is an unblinded, multicenter, 4-by-2
      randomized trial. All-comer patients with indication to coronary stenting are
      randomly treated-balancing randomization-with bare metal stent (no active late
      loss inhibition), Endeavor Sprint zotarolimus-eluting stent (Medtronic, Santa
      Rosa, CA) (mild late loss inhibition), Taxus paclitaxel-eluting stent (Boston
      Scientific, Natick, MA) (moderate late loss inhibition), or Xience V everolimus
      eluting stent (Abbott Vascular, Santa Clara, CA) (high late loss inhibition). At
      30 days, patients in each stent group are randomly allocated to receive 24 or up
      to 6 months of clopidogrel therapy-primary end point randomization. With 1,700
      individuals, this study will have >80% power to detect a 40% difference in the
      primary end point after sample size augmentation of 5% and a background event
      rate of 8%. SUMMARY: The PRODIGY trial aims to assess whether 24 months of
      clopidogrel therapy improves cardiovascular outcomes after coronary intervention
      in a broad all-comer patient population receiving a balanced mixture of stents
      with various anti-intimal hyperplasia potency.

PMID- 21095266
TI  - Rationale and design of a trial on the effect of angiotensin II receptor blockers
      on the function of the systemic right ventricle.
AB  - BACKGROUND: Angiotensin II receptor blockers have been proven to be beneficial in
      left ventricular failure. In patients with a morphologic right ventricle
      supporting the systemic circulation, its efficacy has not yet been established.
      METHODS: We designed a multicenter, prospective, randomized, double-blind,
      placebo-controlled trial studying the effect of valsartan in patients with a
      systemic right ventricle due to a congenitally or surgically corrected
      transposition of the great arteries. The primary end point is the change in right
      ventricular ejection fraction as measured by cardiovascular magnetic resonance or
      multidetector row cardiac computed tomography in case of pacemaker patients.
      CONCLUSION: This large prospective, double-blind, randomized, placebo-controlled
      trial will establish the role of angiotensin II receptor blockers (valsartan) in
      the treatment of patients with a systemic right ventricle.

PMID- 21095267
TI  - Troponin-positive, MB-negative patients with non-ST-elevation myocardial
      infarction: An undertreated but high-risk patient group: Results from the
      National Cardiovascular Data Registry Acute Coronary Treatment and Intervention
      Outcomes Network-Get With The Guidelines (NCDR ACTION-GWTG) Registry.
AB  - BACKGROUND: Despite the 2000 and 2007 redefinition of myocardial infarction (MI),
      patients who are troponin (Tn) positive ([+]) but MB negative ([-]) may not be
      considered to have MI, particularly in the absence of known coronary disease
      (prior MI or revascularization; coronary artery disease [CAD]). How this affects
      treatment and outcomes has not been well described. METHODS: Direct arrival
      patients with non-ST elevation MI (NSTEMI) enrolled in the American College of
      Cardiology NCDR ACTION-GWTG Registry were included. Patients missing marker data
      who were Tn (-) and had CAD were excluded. Troponin (+) patients were categorized
      as MB (+) (n = 11,563) or MB (-) (n = 4,501). Treatments and in-hospital outcomes
      were compared between the 2 groups using logistic regression. RESULTS: Of the
      16,064 NSTEMI patients, 28% were MB (-). The MB (-) patients were older (median
      age 68 vs 65 years) and had more comorbidities (hypertension 71% vs 66%, diabetes
      31% vs 27%, heart failure 22% vs 19%; all Ps < .01). After adjusting for baseline
      characteristics, MB (-) patients were significantly less likely to receive
      clopidogrel, antithrombins, glycoprotein IIb/IIIa antagonists, or angiography
      (all Ps < .001). In-hospital mortality was lower in MB (-) patients (3.8% vs
      4.9%, P < .01), which remained significant after adjusting for baseline variables
      (odds ratio 0, 69, 95% CI 0.6-0.9, P = .002). CONCLUSIONS: Patients without known
      CAD who have NSTEMI and are MB (-) have a higher risk profile but are less likely
      to receive guideline-recommended acute pharmacologic treatment than those who are
      MB (+). Given the relatively high mortality in this group, increased emphasis on
      improving quality of care in Tn (+)/MB (-) patients is warranted.

PMID- 21095268
TI  - "Do GRACE (Global Registry of Acute Coronary events) risk scores still maintain
      their performance for predicting mortality in the era of contemporary management
      of acute coronary syndromes?".
AB  - BACKGROUND: Although the GRACE risk scores (RS) are the preferred scoring system
      for risk stratification in acute coronary syndromes (ACS), little is known
      whether these RS still maintain their performance in the current era. We aimed to
      investigate this issue in a contemporary population with ACS. METHODS: The study
      population composed of patients enrolled in the MASCARA national registry. The
      GRACE RS were calculated for each patient. Discrimination and calibration were
      evaluated with the C statistic and the Hosmer-Lemeshow test, in the whole
      population and according to the type of ACS, risk strata, and whether the patient
      had a history of diabetes and/or chronic renal failure. We determined if left
      ventricular ejection fraction (LVEF) provides incremental prognostic information
      above that established by the RS and whether percutaneous coronary intervention
      (PCI) during admission affects the performance of the score for predicting 6
      month mortality. RESULTS: The 5,985 patients constituted the validation cohort
      for the in-hospital mortality RS and 5,635 the validation cohort for the 6-month
      mortality RS. Overall, both GRACE RS demonstrated excellent discrimination (C >
      0.80) and calibration (all P values in Hosmer-Lemeshow >.1). Although similar
      results were seen in all subgroups, the 6-month mortality RS performed
      significantly less well in patients undergoing PCI compared to those patients who
      did not (C = 0.73 vs 0.76, P < .004). Adding LVEF to the RS did not convey
      significant prognostic information. CONCLUSIONS: The GRACE RS for predicting in
      hospital and 6-month mortality still maintain their excellent performance in a
      contemporary cohort of patients with ACS. Further studies are needed to
      investigate the performance of the 6-month mortality GRACE score in patients
      undergoing in-hospital PCI. Left ventricular ejection fraction did not convey
      significant information over that provided by the RS.

PMID- 21095270
TI  - Does ST resolution achieved via different reperfusion strategies (fibrinolysis vs
      percutaneous coronary intervention) have different prognostic meaning in ST
      elevation myocardial infarction? A systematic review.
AB  - OBJECTIVE: We perform a systematic review to discern if ST resolution achieved
      via percutaneous coronary intervention (PCI) has a different meaning to that
      achieved via fibrinolysis. BACKGROUND: Resolution of ST-segment elevation in
      acute myocardial infarction has been widely used as a surrogate for treatment
      success. A recent randomized study suggested that after primary PCI, the
      prognostic significance of ST resolution may have been overemphasized. METHODS:
      Using the MEDLINE, COCHRANE, EMBASE, and PUBMED databases to search for the
      relevant papers, we analyze the data with a new ST-resolution score. ST
      resolution groups of <30%, 30% to < 70%, and >= 70% are given scores of 1, 2, and
      3 respectively, whereas ST-resolution groups reported as < 50% are scored as 1.5,
      and >= 50% scored as 2.5. RESULTS: We identify 18 fibrinolysis cohorts (32,341
      patients) and 5 PCI cohorts (1,913 patients). The mean ST-resolution score
      weighted for the number of patients in each cohort is 1.87 +/- 0.15 for PCI and
      1.66 +/- 0.20 for fibrinolysis (P < .001). The raw combined 30-day mortality is
      4.9% with fibrinolysis and 4.3% with PCI (P = .452 by Poisson regression). There
      is a linear relationship with lower 30-day mortality associated with higher ST
      resolution score. The regression line for the PCI cohorts almost overlaps with
      that from the fibrinolysis cohorts. On multivariate regression, only ST
      resolution score is significant in predicting 30-day mortality. When tested, the
      interaction term (treatment group * ST resolution score) is never a significant
      predictor (P > .25 in all models). CONCLUSION: ST resolution after different
      reperfusion therapies has similar prognostic meaning.

PMID- 21095269
TI  - Early and late outcome prediction of death in the emergency room setting by point
      of-care and laboratory assays of cardiac troponin I.
AB  - BACKGROUND: Point-of-care (POC) assays of cardiac troponins are common in the
      emergency department setting. The question raised was as follows: What is the
      clinical impact of the results of POC assays of cardiac troponins as compared
      with sensitive laboratory assays? METHODS: Patients admitted consecutively to the
      emergency department (N = 1,069) and on whom cardiac troponins were requested as
      part of their clinical work-up were included. Cardiac troponin I (cTnI) was
      measured by the POC assays-i-Stat (Abbott Diagnostics, Abbott Park, IL) and
      Stratus CS (Siemens Healthcare Diagnostics, Deerfield, IL)-and by the laboratory
      assays-Access AccuTnI (Beckman Coulter, Fullerton, CA) and Architect cTnI (Abbott
      Diagnostics). Results were related to early (14 days) and late outcome (median
      3.3 months, range 0.1-35) as to death. RESULTS: The laboratory assays identified
      more patients (P < .001) with elevated levels than the two POC assays (39%-74% vs
      20%-27%). Adopting the 99th percentiles upper reference limit, the Access AccuTnI
      identified 88% and Architect cTnI identified 81% of all patients who died of
      cardiovascular disease as compared with 50% and 54% for i-Stat and Stratus CS,
      respectively (P < .001). Negative predictive values for the laboratory assays
      were 97% as compared with 89% to 93% for the POC assays. Negative likelihood
      ratios were 0.25 (CI 0.15-0.041) and 0.59 to 0.68 (CI 0.47-0.79), respectively.
      CONCLUSIONS: The current POC cTnI assays are less sensitive for outcome
      prediction of patients with myocardial injury. The clinical judgment of the
      patient with suspected myocardial ischemia should not solely rely on results from
      POC assays. If a clinical suspicion of myocardial injury remains despite negative
      cTnI results with the POC assays, such results should be complemented by results
      from sensitive laboratory assays.

PMID- 21095271
TI  - Can an elderly woman's heart be too strong? Increased mortality with high versus
      normal ejection fraction after an acute coronary syndrome. The Global Registry of
      Acute Coronary Events.
AB  - BACKGROUND: Coronary artery disease is the leading cause of death in women. We
      sought to validate previous clinical experience in which we have observed that
      elderly women with a very high left ventricular ejection fraction (LVEF) are at
      increased risk of death compared with elderly women with acute coronary syndromes
      with a normal LVEF. METHODS: Data from 5,127 elderly female patients (age >65
      years) enrolled in the Global Registry of Acute Coronary Events were collected.
      Patients were divided into 3 groups based on their LVEF: group I had a low
      ejection fraction (<55%), group II had a normal ejection fraction (55%-65%), and
      group III had a high ejection fraction (>65%). chi2 test and multiple logistic
      regression analysis were performed. The main outcome measures were death in
      hospital and death, stroke, rehospitalization, and myocardial infarction at 6
      month follow-up. RESULTS: Hospital mortality was 12% in group I. Patients in
      group III were more likely to die in-hospital than those in group II (P = .003).
      Multivariable logistic regression showed that high ejection fraction was an
      independent predictor of hospital death (odds ratio [OR] 2.5, 95% CI [CI] 1.2
      5.2, P = .01), 6-month death (OR 2.0, 95% CI 1.1-3.4, P = .01), and cardiac
      arrest/ventricular fibrillation (OR 2.5, 95% CI 1.2-5.0, P = .01) compared with
      the normal ejection fraction group. CONCLUSIONS: Having a very high LVEF (> 65%)
      is associated with worse survival and higher rates of sudden cardiac death than
      an LVEF considered to be in the reference range.

PMID- 21095272
TI  - Association between smoking, outcomes, and early clopidogrel use in patients with
      acute coronary syndrome: insights from the Global Registry of Acute Coronary
      Events.
AB  - BACKGROUND: Smoking induces CYP1A2, thereby enhancing clopidogrel conversion to
      its active metabolite. We sought to determine the association between clopidogrel
      use and clinical outcomes in smokers versus nonsmokers with a broad spectrum of
      acute coronary syndrome (ACS). METHODS: We examined the association between early
      clopidogrel use in-hospital and 6-month outcomes among 44,426 patients with ACS
      in relation to smoking status in the Global Registry of Acute Coronary Events. We
      tested for heterogeneity of clopidogrel effect among smokers versus nonsmokers in
      separate multivariable models that adjusted for (1) established prognosticators
      in the Global Registry of Acute Coronary Events risk score and (2) independent
      predictors of major bleeding. RESULTS: Rates of in-hospital mortality,
      death/myocardial infarction, and major bleeding were 4.3%, 5.9%, and 2.5%,
      respectively. Current smokers (n = 12,149) were more likely to be younger men
      without documented vascular disease; had lower rates of hypertension,
      hyperlipidemia, and diabetes; and more frequently presented with ST elevation
      (all P < .0001). Early clopidogrel use (55%) was associated with a reduction in
      the composite endpoint of mortality and myocardial infarction both in-hospital
      and at 6 months among current smokers and nonsmokers. There was no interaction
      between current smoking and clopidogrel use for ischemic endpoints. Major
      bleeding associated with early clopidogrel use was actually lower among current
      smokers compared with nonsmokers. CONCLUSIONS: Despite prior observations of
      smoking-enhanced clopidogrel effects, early clopidogrel use among smokers
      presenting with ACS compared with nonsmokers was not independently associated
      with a greater reduction in cardiovascular events. In contrast with nonsmokers,
      clopidogrel use among smokers was not associated with excess bleeding, perhaps
      because of unmeasured confounders.

PMID- 21095273
TI  - Early hemodynamic and neurohormonal response after transcatheter aortic valve
      implantation.
AB  - BACKGROUND: The conventional surgical aortic bioprostheses used for treatment of
      aortic stenosis (AS) are inherently stenotic in nature. The more favorable
      mechanical profile of the Medtronic CoreValve bioprosthesis may translate into a
      better hemodynamic and neurohormonal response. PATIENTS AND METHODS: The early
      hemodynamic and neurohormonal responses of 56 patients who underwent successful
      transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve
      bioprosthesis for severe symptomatic AS were compared with those of 36 patients
      who underwent surgical aortic valve replacement (SAVR) using tissue valves in the
      same period. RESULTS: At baseline, patients in the TAVI and SAVR group had
      comparable indexed aortic valve area (0.33 +/- 0.1 vs 0.34 +/- 0.1 cm2 ,
      respectively; P = .69) and mean transvalvular gradient (51.1 +/- 16.5 vs 53.1 +/-
      14.3 mm Hg, respectively; P = .56). At 30-day follow-up, mean transvalvular
      gradient was lower in the TAVI group than in the SAVR group (10.3 +/- 4 vs 13.1
      +/- 6.2 mm Hg, respectively; P = .015), and the indexed aortic valve area was
      larger in the TAVI group (1.0 +/- 0.14 vs 0.93 +/- 0.13 cm2/m2; P = .017). There
      was a trend toward a higher incidence of moderate patient-prosthesis mismatch in
      the surgical group compared with the TAVI group (30.5% vs 17.8%, respectively; P
      = .11). The overall incidence of prosthetic regurgitation (any degree) was higher
      in the TAVI group than in the SAVR group (85.7% vs 16.7%, respectively; P <
      .00001). The left ventricular mass index decreased after TAVI (175.1 +/- 61.8 vs
      165.6 +/- 57.2 g/m2; P = .0003) and remained unchanged after SAVR (165.1 +/- 50.6
      vs 161 +/- 64.8 g/m2; P = .81). Similarly, NT-ProBNP decreased after TAVI (3,479
      +/- 2,716 vs 2,533 +/- 1,849 pg/mL; P = .033) and remained unchanged after SAVR
      (1,836 +/- 2,779 vs 1,689 +/- 1,533 pg/mL; P = .78). There was a modest
      correlation between natriuretic peptides and left ventricular mass index in the
      whole cohort (r = 0.4, P = .013). CONCLUSION: In patients with severe AS, TAVI
      resulted in lower transvalvular gradients and higher valve areas than SAVR. Such
      hemodynamic performance after TAVI may have contributed to early initiation of a
      reverse cardiac remodeling process and a decrease in natriuretic peptides.

PMID- 21095274
TI  - Ventricular response to stress predicts outcome in adult patients with a systemic
      right ventricle.
AB  - BACKGROUND: Previous studies demonstrated that ventricular response to stress
      cardiovascular magnetic resonance (CMR) is frequently abnormal in patients with a
      systemic right ventricle (RV). However, the clinical implications of these
      findings remained unknown. We sought to evaluate whether abnormal response to
      stress CMR predicts adverse outcome in patients with a systemic RV. METHODS:
      Thirty-nine adult patients (54% male; mean age 26, range 18-65 years) with a
      systemic RV underwent stress CMR to determine the response of RV volumes and
      ejection fraction (EF). During follow-up, cardiac events, defined as
      hospitalization for heart failure, cardiac surgery, aborted cardiac arrest, or
      death, were recorded. The prognostic value of an abnormal response to stress,
      defined as lack of a decrease in RV end-systolic volume (ESV) or lack of an
      increase in RV EF, was assessed. RESULTS: We frequently observed an abnormal
      response to stress, as RV ESV did not decrease in 17 patients (44%), and RV EF
      did not increase in 15 patients (38%). After a mean follow-up period of 8.1
      years, 8 (21%) patients had reached the composite end point. The inability to
      decrease RV ESV during stress was predictive for cardiac events with a hazard
      ratio of 2.3 (95% CI 1.19-88.72, P = .034), as was the inability to increase RV
      EF with a hazard ratio of 2.3 (95% CI 1.31-81.59, P = .027). CONCLUSIONS: Stress
      CMR potentially has important prognostic value in patients with a systemic RV.
      Patients with a systemic RV who show abnormal cardiac response to stress have a
      substantially higher risk of adverse outcome.

PMID- 21095275
TI  - Echocardiographic left atrial reverse remodeling after catheter ablation of
      atrial fibrillation is predicted by preablation delayed enhancement of left
      atrium by magnetic resonance imaging.
AB  - BACKGROUND: Atrial fibrosis is a hallmark of atrial structural remodeling (SRM)
      and leads to structural and functional impairment of left atrial (LA) and
      persistence of atrial fibrillation (AF). This study was conducted to assess LA
      reverse remodeling after catheter ablation of AF in mild and moderate-severe LA
      SRM. METHODS: Catheter ablation was performed in 68 patients (age 62 +/- 14
      years, 68% males) with paroxysmal (n = 26) and persistent (n = 42) AF. The
      patients were divided into group 1 with mild LA SRM (<10%, n = 31) and group 2
      with moderate-severe LA SRM (>10%, n = 37) by delayed enhancement magnetic
      resonance imaging (DEMRI). Two-dimensional echocardiography, LA strain, and
      strain rate during left ventricular systole by velocity vector imaging were
      performed pre and at 6 +/- 3 months postablation. The long-term outcome was
      monitored for 12 months. RESULTS: Patients in group 1 were younger (57 +/- 15 vs
      66 +/- 13 years, P = .009) with a male predominance (80% vs 57%, P < .05) as
      compared to group 2. Postablation, group 1 had significant increase in average LA
      strain (Delta?: 14% vs 4%, P < .05) and strain rate (Delta?: 0.5 vs 0.1 cm/s, P <
      .05) as compared to group 2. There was a trend toward more patients with
      persistent AF in group 2 (68% vs 55%, P = .2), but it was not statistically
      significant. Group 2 had more AF recurrences (41% vs 16%, P = .02) at 12 months
      after ablation. CONCLUSION: Mild preablation LA SRM by DEMRI predicts favorable
      LA structural and functional reverse remodeling and long-term success after
      catheter ablation of AF, irrespective of the paroxysmal or persistent nature of
      AF.

PMID- 21095276
TI  - Generalizability and longitudinal outcomes of a national heart failure clinical
      registry: Comparison of Acute Decompensated Heart Failure National Registry
      (ADHERE) and non-ADHERE Medicare beneficiaries.
AB  - BACKGROUND: Clinical registries are used increasingly to analyze quality and
      outcomes, but the generalizability of findings from registries is unclear.
      METHODS: We linked data from the Acute Decompensated Heart Failure National
      Registry (ADHERE) to 100% fee-for-service Medicare claims data. We compared
      patient characteristics and inpatient mortality of linked and unlinked ADHERE
      hospitalizations; patient characteristics, readmission, and postdischarge
      mortality of linked ADHERE patients to a random 20% sample of Medicare
      beneficiaries hospitalized for heart failure; and characteristics of Medicare
      sites participating and not participating in ADHERE. RESULTS: Among 135,667
      ADHERE records for eligible patients >= 65 years, we matched 104,808 (77.3%)
      records to fee-for-service Medicare claims, representing 82,074 patients. Linked
      hospitalizations were more likely than unlinked hospitalizations to involve women
      and white patients; there were no meaningful differences in other patient
      characteristics. In-hospital mortality was identical for linked and unlinked
      hospitalizations. In Medicare, ADHERE patients had slightly lower unadjusted
      mortality (4.4% vs 4.9% in-hospital, 11.2% vs 12.2% at 30 days, 36.0% vs 38.3% at
      1 year [P < .001]) and all-cause readmission (22.1% vs 23.7% at 30 days, 65.8% vs
      67.9% at 1 year [P < .001]). After risk adjustment, modest but statistically
      significant differences remained. ADHERE hospitals were more likely than non
      ADHERE hospitals to be teaching hospitals, have higher volumes of heart failure
      discharges, and offer advanced cardiac services. CONCLUSION: Elderly patients in
      ADHERE are similar to Medicare beneficiaries hospitalized with heart failure.
      Differences related to selective enrollment in ADHERE hospitals and self
      selection of participating hospitals are modest.

PMID- 21095278
TI  - Cardiopulmonary exercise testing characteristics in heart failure patients with
      and without concomitant chronic obstructive pulmonary disease.
AB  - BACKGROUND: The assessment of aerobic exercise capacity is an important component
      in the clinical management of patients with heart failure (HF). Although a
      significant percentage of patients diagnosed with HF also present with chronic
      obstructive pulmonary disease (COPD) comorbidity, the combined impact of these
      chronic conditions on the aerobic exercise response is unknown and is therefore
      the purpose of the present investigation. METHODS: Sixty-nine subjects with HF
      and COPD were matched to 69 subjects solely diagnosed with HF according to age,
      sex, and HF etiology. All subjects underwent resting pulmonary function and
      diffusion capacity testing, echocardiography with tissue Doppler imaging, and
      cardiopulmonary exercise testing (CPX). RESULTS: Subjects with COPD comorbidity
      had significantly lower pulmonary function testing and diffusion capacity values
      versus HF alone (P < .05). In addition, subjects with both HF and COPD had
      significantly higher pulmonary artery systolic pressures (51.9 +/- 9.0 vs 37.0 +/
      7.8 mm Hg, P < .001) as assessed by pulsed Doppler echocardiography.
      Cardiopulmonary exercise testing revealed a significantly poorer response in
      subjects with HF and COPD by all variables that were analyzed, including peak
      oxygen consumption (12.1 +/- 4.3 vs 16.3 +/- 4.3 mL kg-1 min-1, P < .001), minute
      ventilation/carbon dioxide production slope (42.7 +/- 7.4 vs 33.3 +/- 6.6, P <
      .001) and heart rate recovery at 1 minute (12.1 +/- 2.5 vs 14.2 +/- 2.9 beats, P
      < .001). CONCLUSIONS: Patients with HF and the comorbidity of COPD have
      significantly impaired CPX responses. This novel finding may impact the clinical
      interpretation of CPX data in patients with HF who also present with this chronic
      pulmonary condition.

PMID- 21095277
TI  - Serum 25-hydroxyvitamin D concentration is associated with functional capacity in
      older adults with heart failure.
AB  - BACKGROUND: Vitamin D is a fat-soluble hormone necessary for calcium homeostasis.
      Recently, studies have demonstrated that vitamin D may be important to the health
      of the cardiovascular system. METHODS: Adults >= 50 years of age with heart
      failure were recruited for assessment of serum 25-hydroxyvitamin D (25OHD)
      concentrations. Cardiopulmonary exercise testing was used to assess functional
      capacity. Proximal muscle strength was evaluated with a Biodex isokinetic
      dynamometer [corrected] (Biodex, Shirley, NY), and health status was assessed
      with the Kansas City Cardiomyopathy Questionnaire. Univariate associations
      between physical performance and health status measures and 25OHD followed by a
      linear regression model were used to study associations, adjusting for other
      potential explanatory variables. RESULTS: Forty adults 67.8 +/- 10.9 years of age
      (55% women and 57.5% African American) with mean ejection fraction 40% were
      analyzed (New York Heart Association class II in 70% and class III in 30%).
      Comorbidities included 77.5% hypertension and 47.5% diabetes. The mean 25OHD
      concentration was 18.5 +/- 9.1 ng/mL, and mean peak Vo2, 14 +/- 4 mL/kg/min. In
      univariate regression analysis, 25OHD was positively associated with peak Vo2 (P
      = .045). Multivariable regression analysis sustained positive association between
      25OHD and peak Vo2 (P = .044) after adjusting for age, race, and respiratory
      exchange ratio (adjusted R2 = 0.32). Association between proximal muscle strength
      with the 25OHD concentration was not significant. The Kansas City Cardiomyopathy
      Questionnaire physical limitation domain score was negatively associated with
      25OHD (P = .04) but was not sustained in multivariable analysis. CONCLUSIONS: 25
      Hydroxyvitamin D may be an important marker or modulator of functional capacity
      in patients with heart failure. Randomized controlled trials are needed to assess
      the effect of vitamin D repletion on functional performance.

PMID- 21095279
TI  - Clinical and prognostic role of pressure-volume relationship in the
      identification of responders to cardiac resynchronization therapy.
AB  - BACKGROUND: The identification of responders remains challenging in cardiac
      resynchronization therapy (CRT). Pressure-volume relationship (PVR) is a method
      to evaluate left ventricular myocardial contractility during stress. The aim of
      the study was to assess the role of PVR to identify responders to CRT. METHODS:
      Seventy-two patients (57% with ischemic etiology) referred to CRT: ejection
      fraction <= 35%, New York Heart Association >= III and QRS duration >= 120
      milliseconds, underwent dobutamine stress echocardiography (up to 40 MUg/kg per
      minute). PVR was defined as systolic cuff pressure/end-systolic volume index
      difference between rest-peak dobutamine stress echocardiography. Responders were
      identified by clinical and/or echocardiographic (end-systolic volume decrease >=
      15%) follow-up criteria. We divided retrospectively the patient population into 2
      groups, accordingly to the presence of myocardial contractile reserve that was
      set at the value of PVR (0.72 mm Hg/mL per square meter) obtained by a receiver
      operating characteristic analysis. RESULTS: During a median follow-up of 12
      months, 8 patients (11%) died. Patients with lower PVR, showed higher brain
      natriuretic peptide levels (853 +/- 1211 vs 342 +/- 239, P = .044) larger left
      ventricular end-diastolic (196 +/- 82 mL vs 152 +/- 39 mL, P = .005) and end
      systolic (147 +/- 66 vs 112 +/- 30 mL, P = .006) volumes. Intraventricular
      dyssynchrony was similar in the 2 groups (88 +/- 45 vs 70 +/- 32 milliseconds, P
      = .175). Patients with higher PVR presented a larger incidence of clinical (86%
      vs 46% P < .001), and echocardiographic responders to CRT (79% vs 40%, P = .002).
      Event-free survival was significantly better in patients with higher PVR (log
      rank = 5.78, P = .01). CONCLUSION: Patients with preserved contractility,
      assessed by PVR during stress echocardiography show a favor clinical outcome and
      left ventricular reverse remodeling after CRT. In particular, PVR may have a
      significant clinical role in patients undergoing CRT, providing critical
      information for risk stratification.

PMID- 21095280
TI  - Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1(c)
      levels in patients with chronic heart failure.
AB  - BACKGROUND: It has been reported that mineralocorticoid receptor antagonist
      improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1(c)
      (HbA1(c)) levels have been reported to be an independent risk factor for
      mortality in CHF, suggesting the important role of insulin resistance in CHF. We
      compared the metabolic effect of a selective mineralocorticoid receptor blocker
      eplerenone with spironolactone in CHF patients. METHODS: One hundred seven stable
      outpatients with mild CHF, who were already receiving standard therapy for CHF,
      were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma
      levels of B-type natriuretic peptide, adiponectin, HbA1(c) and cortisol were
      measured before and after 4 months treatment with spironolactone or eplerenone.
      RESULTS: There were no differences in baseline characteristics including
      hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both
      groups, plasma B-type natriuretic peptide levels were significantly decreased and
      plasma aldosterone levels were significantly increased after 4 months. In
      patients receiving spironolactone (n = 34), plasma adiponectin levels were
      significantly decreased (12.6 +/- 1.4-11.2 +/- 1.3 MUg/mL, P < .0001) and HbA1(c)
      and cortisol levels were significantly increased (5.61 +/- 0.1-5.8 +/- 0.1%, P <
      .0001, 11.3 +/- 0.8-14.7 +/- 1.3 MUg/dL, P = .003, respectively). In patients
      receiving spironolactone, there was a significant positive correlation between
      the change in cortisol and the change in HbA1(c) (r = 0.489, P = .003). In
      contrast, in patients receiving eplerenone (n = 73), plasma levels of
      adiponectin, HbA1(c) and cortisol did not change. CONCLUSION: These findings
      indicated that the metabolic effect of eplerenone differed from that of
      spironolactone and that eplerenone had a superior metabolic effect especially on
      HbA1(c) in CHF patients.

PMID- 21095281
TI  - Prognostic usefulness of the functional aerobic reserve in patients with heart
      failure.
AB  - BACKGROUND: Peak oxygen consumption derived from cardiopulmonary exercise (CPX)
      testing provides important prognostic information in patients with heart failure
      (HF). The oxygen consumption at the ventilatory threshold (VT) has also been
      shown to be prognostic. However, the VT cannot always be detected in patients
      with HF. Other variables such as the difference between peak oxygen consumption
      and oxygen consumption at the VT (termed the functional aerobic reserve [FAR])
      may also provide prognostic information. The purpose of this study was to
      determine the prognostic value of an undetectable VT and FAR. METHODS: Eight
      hundred seventy-four patients with chronic, systolic HF (70% male, age 54 +/- 14
      years, ejection fraction 29% +/- 12%) underwent CPX and were tracked for 2 years
      for major events (death, transplant, and left ventricular assist device
      implantation). RESULTS: Patients were divided into 2 subgroups based on whether
      VT could be detected or not. There were 141 major events during the 2-year follow
      up. Kaplan-Meier analysis for the 2 VT subgroups demonstrated worse prognoses for
      patients with a nondetectable VT versus those with a detectable VT (P < .001).
      Based on receiver operating characteristic curve analysis (FAR = 0 mlO2 kg-1 min
      1 for patients with undetectable VT), the optimal cut-point for FAR was <=/>3
      mlO2 kg min-1 (sensitivity/specificity 69%/60%). Cox regression analysis
      identified the FAR as a significant univariate predictor of risk and was retained
      in multivariate analysis. CONCLUSION: In conclusion, these data reveal that an
      undetectable VT and the FAR during CPX testing can provide useful prognostic
      information in patients with HF.

PMID- 21095282
TI  - Uric acid level and allopurinol use as risk markers of mortality and morbidity in
      systolic heart failure.
AB  - BACKGROUND: Previous studies have not extensively examined the association of
      hyperuricemia and adverse outcomes in systolic heart failure (HF) in relation to
      xanthine oxidase inhibitor therapy. METHODS: The Prospective Randomized
      Amlodipine Survival Evaluation study included New York Heart Association class
      IIIB or IV patients with left ventricular ejection fraction <30%. For analysis,
      the population was divided into uric acid quartiles among nonallopurinol users
      (2.2-7.1, >7.1-8.6, >8.6-10.4, >10.4 mg/dL) and those using allopurinol.
      Multivariate Cox regression modeling was performed to identify predictors of
      mortality. Uric acid quartile and allopurinol groups were referenced to the
      lowest uric acid quartile. RESULTS: A total of 1,152 patients were included. In
      general, patients in the allopurinol group and in the highest uric acid quartile
      had indicators of more severe HF, including worse renal function and greater
      proportion of New York Heart Association class IV patients, and greater diuretic
      use. The allopurinol group and highest uric acid quartile had the highest total
      mortality (41.7 and 42.4 per 100 person-years, respectively) and combined
      morbidity/mortality (45.6 and 51.0 per 100 person-years, respectively).
      Allopurinol use and highest uric acid quartile were independently associated with
      mortality (hazard ratio [HR] 1.65, 95% CI 1.22-2.23, P = .001 and HR 1.35, 95% CI
      1.07-1.72, P = .01, respectively) and combined morbidity/mortality (uric acid
      quartile 4 vs 1: HR 1.32, 95% CI 1.06-1.66, P = .02; allopurinol use: HR 1.48,
      95% CI 1.11-1.99, P = .008). CONCLUSION: Elevated uric acid level was
      independently associated with mortality in patients with severe systolic HF, even
      when accounting for allopurinol use.

PMID- 21095284
TI  - Who is missing from the measures? Trends in the proportion and treatment of
      patients potentially excluded from publicly reported quality measures.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services provides public
      reporting on the quality of hospital care for patients with acute myocardial
      infarction (AMI). The Centers for Medicare and Medicaid Services Core Measures
      allow discretion in excluding patients because of relative contraindications to
      aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors. We describe
      trends in the proportion of patients with AMI with contraindications that could
      lead to discretionary exclusion from public reporting. METHODS: We completed
      cross-sectional analyses of 3 nationally representative data cohorts of AMI
      admissions among Medicare patients in 1994-1995 (n = 170,928), 1998-1999 (n =
      27,432), and 2000-2001 (n = 27,300) from the national Medicare quality
      improvement projects. Patients were categorized as ineligible (eg, transfer
      patients), automatically excluded (specified absolute medical contraindications),
      discretionarily excluded (potentially excluded based on relative
      contraindications), or "ideal" for treatment for each measure. RESULTS: For 4 of
      5 measures, the percentage of discretionarily excluded patients increased over
      the 3 periods (admission aspirin 15.8% to 16.9%, admission beta-blocker 14.3% to
      18.3%, discharge aspirin 10.3% to 12.3%, and angiotensin-converting enzyme
      inhibitors 2.8% to 3.9%; P < .001). Of patients potentially included in measures
      (those who were not ineligible or automatically excluded), the discretionarily
      excluded represented 25.5% to 69.2% in 2000-2001. Treatment rates among patients
      with discretionary exclusions also increased for 4 of 5 measures (all except
      angiotensin-converting enzyme inhibitors). CONCLUSIONS: A sizeable and growing
      proportion of patients with AMI have relative contraindications to treatments
      that may result in discretionary exclusion from publicly reported quality
      measures. These patients represent a large population for which there is
      insufficient evidence as to whether measure exclusion or inclusion and treatment
      represents best care.

PMID- 21095285
TI  - Association of prior coronary artery bypass graft surgery with quality of care of
      patients with non-ST-segment elevation myocardial infarction: a report from the
      National Cardiovascular Data Registry Acute Coronary Treatment and Intervention
      Outcomes Network Registry-Get With the Guidelines.
AB  - BACKGROUND: The American College of Cardiology/American Health Association
      guidelines recommend both an early invasive strategy and administration of
      antiplatelet/anticoagulant therapy for high-risk patients in the absence of
      contraindications. Little is known about adherence to guideline recommendations
      in patients with prior coronary artery bypass graft (CABG) surgery presenting
      with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We
      analyzed 47,557 patients with NSTEMI in the 2007-2008 National Cardiovascular
      Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry
      Get With The Guidelines. Treatment patterns were compared between patients with
      and without prior CABG surgery. Multivariable regression with generalized
      estimating equations evaluated the association between prior CABG and in-hospital
      outcomes. RESULTS: In this study, 8,790 NSTEMI patients (18.5%) had a history of
      CABG surgery. Prior CABG surgery was associated with a significantly lower
      adjusted likelihood of early cardiac catheterization (adjusted odds ratio [OR]
      0.88, 95% CI 0.83-0.92), higher rates of short-term clopidogrel use (adjusted OR
      1.08, 95% CI 1.02-1.14), and comparable use of anticoagulant therapy (adjusted OR
      0.96, 95% CI 0.88-1.04). Adjusted risks of bleeding and in-hospital mortality did
      not differ significantly between the 2 groups (adjusted ORs 1.00, 95% CI 0.92
      1.11 and 0.99, 95% CI 0.87-1.11, respectively). CONCLUSIONS: Patients with prior
      CABG surgery presenting with NSTEMI are often felt to be at high risk for adverse
      outcomes and therefore require aggressive treatment. Our study indicates that
      they are less likely to undergo guideline-recommended early cardiac
      catheterization but equally or more likely to receive guideline-recommended
      antiplatelet and anticoagulant therapy. This risk-treatment paradox, however,
      does not appear to negatively influence short-term clinical outcomes.

PMID- 21095283
TI  - Physician diagnosis of overweight status predicts attempted and successful weight
      loss in patients with cardiovascular disease and central obesity.
AB  - INTRODUCTION: Despite the association of central obesity with adverse outcomes,
      most patients with cardiovascular disease (CVD) are unable to successfully lose
      weight. We undertook this analysis to evaluate the effect of motivational
      factors, and clinical factors, including physician diagnosis of overweight, on
      weight loss in patients with CVD and central obesity in the United States.
      METHODS AND RESULTS: We used data from the National Health and Nutrition
      Examination Survey 1999 to 2004. Waist circumference >= 102 cm in men and >= 88
      cm in women were used to classify central obesity. We examined demographic,
      motivational and clinical determinants of attempted and successful weight loss
      using multivariable logistic regression. Successful weight loss was defined as >=
      5% weight loss in the preceding year. There were 907 respondents with CVD and
      central obesity of which 78% were aware of their overweight status and 80% were
      desirous to weigh less. Despite this awareness and desire, only 49% of centrally
      obese adults had attempted weight loss in the last year. Only 62% (n = 584)
      reported that they had been informed that they were overweight by a physician. On
      multivariable analysis, physician diagnosis of overweight was a significant
      predictor of weight loss attempts (OR 2.42, 95% CI 1.44-4.09, P = .006) and
      successful weight loss (OR 2.70, 95% CI 1.40-5.19, P = .001). CONCLUSION: In a
      nationally representative sample of adults with CVD and central obesity,
      physician diagnosis of overweight status emerged as a significant predictor of
      attempted and successful weight loss.

PMID- 21095286
TI  - Increasing rates of angioplasty versus bypass surgery in Canada, 1994-2005.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being
      offered to patients with coronary artery disease. The purpose of this study was
      to determine the impact of this change in coronary revascularization strategy on
      PCI and coronary artery bypass grafting (CABG) utilization across Canada.
      METHODS: All cases of PCI and isolated CABG between years 1994 and 2005 were
      identified through the Canadian Institute for Health Information. Age- and sex
      standardized rates of PCI and CABG per 100,000 population as well as PCI-to-CABG
      ratios were calculated by year and province and across age, sex, income,
      diabetes, and recent acute coronary syndrome subgroups. In addition, risk
      adjusted rates of in-hospital mortality after PCI and CABG were reported by year.
      RESULTS: Between 1994 and 2005, PCI rates increased from 85.6/100,000 to
      186.7/100,000 (P < .001), whereas CABG rates remained stable (75.6/100,000
      70.8/100,000; P = .43), resulting in an increase in PCI-to-CABG ratio (1.13-2.64;
      P < .001). Significant increases in PCI-to-CABG ratios were seen across all
      provinces (except Newfoundland and Alberta), as well as across all age, sex,
      income, diabetes, and recent acute coronary syndrome categories. Decline in risk
      adjusted in-hospital mortality was seen after both CABG (3.9%-2.2%; P < .001) and
      PCI (1.6%-1.3%; P < .001) but appeared larger after CABG. CONCLUSIONS: Since
      1994, rates of PCI have increased significantly as compared to CABG. During the
      same period, greater declines in risk-adjusted rates of in-hospital mortality
      were seen among CABG versus PCI patients. Further study is needed to determine
      the appropriateness of PCI and CABG rates in terms of clinical outcomes and
      resource utilization.

PMID- 21095287
TI  - Thrombus aspiration followed by direct stenting: a novel strategy of primary
      percutaneous coronary intervention in ST-segment elevation myocardial infarction.
      Results of the Polish-Italian-Hungarian RAndomized ThrombEctomy Trial (PIHRATE
      Trial).
AB  - BACKGROUND: Previous studies with thrombectomy showed different results, mainly
      due to use of thrombectomy as an additional device not instead of balloon
      predilatation. The aim of the present study was to assess impact of aspiration
      thrombectomy followed by direct stenting. METHODS: Patients with ST elevation
      myocardial infarction (STEMI) <6 hours from pain onset and occluded infarct
      related artery in baseline angiography were randomized into aspiration
      thrombectomy followed by direct stenting (TS, n = 100) or standard balloon
      predilatation followed by stent implantation (n = 96). The primary end point of
      the study was the electrocardiographic ST-segment elevation resolution >70% (STR
      > 70%) 60 minutes after primary angioplasty (percutaneous coronary intervention
      [PCI]). Secondary end points included angiographic myocardial blush grade (MBG)
      after PCI, combination of STR > 70% immediately after PCI and MBG grade 3
      (optimal myocardial reperfusion), Thrombolysis In Myocardial Infarction flow
      after PCI, angiographic complications, and in-hospital major adverse cardiac
      events. RESULTS: Aspiration thrombectomy success rate was 91% (crossing of the
      lesion with thrombus reduction and flow restoration). There was no significant
      difference in STR >= 70% after 60 minutes (53.7% vs 35.1%, P = .29). STR > 70%
      immediately after PCI (41% vs 26%, P < .05), MBG grade 3 (76% vs 58%, P < .03),
      and optimal myocardial reperfusion (35.1% vs 11.8%, P < .001) were more frequent
      in TS. There was no difference in between the groups in 6-month mortality (4% vs
      3.1%, P = .74) and reinfarction rate (1% vs 3.1%, P = .29). CONCLUSIONS:
      Aspiration thrombectomy and direct stenting is safe and effective in STEMI
      patients with early presentation (<6 hours). The angiographic parameters of
      microcirculation reperfusion and ECG ST-segment resolution directly after PCI
      were significantly better in thrombectomy group despite the lack of the
      difference in ST-segment resolution 60 minutes after PCI.

PMID- 21095288
TI  - Long-term outcomes after drug-eluting stent for the treatment of ostial left
      anterior descending coronary artery lesions.
AB  - BACKGROUND: Although drug-eluting stents (DES) have reduced restenosis in a broad
      range of lesions, there is limited data, from relatively small studies, on the
      safety and efficacy of DES for isolated ostial left anterior descending (LAD)
      stenoses. In addition, in the setting of these high-risk lesions, there is the
      issue of the potential involvement of the left main (LM) bifurcation, requiring
      subsequent revascularization for a lesion involving this critical location.
      METHODS: Patients with a de novo isolated unprotected ostial LAD stenoses treated
      with DES were included. Evaluated end points were cardiac death, nonfatal
      myocardial infarction, overall target lesion revascularization (TLR), and the
      reintervention for a restenotic lesion located at the LM segment adjacent to the
      stent (TLR-LM). RESULTS: A total of 162 patients were included: 95 underwent
      focal ostial LAD stenting and 67 stenting from the distal LM into the LAD ostium.
      The 2-year Kaplan-Meier estimates of cardiac death, nonfatal myocardial
      infarction, overall TLR, and TLR-LM were 2.6%, 2.1%, 8.3%, and 4.7%,
      respectively. Overall TLR and TLR-LM rates were higher in the focal ostial LAD
      stenting group. There was a trend toward an independent increased risk of TLR
      associated with focal ostial stenting. In addition, final minimal luminal
      diameter trended to be independently associated with TLR. CONCLUSION: The present
      study showed that DES for isolated ostial LAD lesions is a feasible, safe, and
      effective treatment strategy. In addition, this study suggested the hypothesis
      that a default distal LM-LAD stenting, rather than focal ostial stenting, might
      provide more favorable outcomes. Nevertheless, larger specifically designed
      studies are needed.

PMID- 21095289
TI  - Differential effects of post-dilation after stent deployment in patients
      presenting with and without acute myocardial infarction.
AB  - BACKGROUND: In the practice of percutaneous coronary intervention, post-dilation
      often is performed after stent deployment to improve stent expansion. However,
      aggressive mechanical expansion is a risk factor of distal embolization and
      microvascular injury, especially for patients with acute myocardial infarction
      (AMI). Few studies have investigated the effects of post-dilation on medium-term
      clinical outcomes. METHODS AND RESULTS: Patients enrolled in the multicenter
      NHLBI Dynamic Registry between 2001 and 2006 were evaluated. Patients who were
      treated with >= 1 stent were studied. Patients with cardiogenic shock or history
      of coronary artery bypass graft surgery were excluded. Patients were followed up
      to 1 year. Because of the significant statistical interaction (P = .02) between
      post-dilation and AMI status on the hazard of death/myocardial infarction (MI),
      post-dilation effects were estimated separately for patients who did and did not
      present with an AMI. Among the 1,358 patients who presented with an AMI, post
      dilation was associated with a significantly higher risk of death/MI (hazard
      ratio [HR] = 1.78, 95% CI 1.12-2.83, P = .01), not associated with the risk of
      repeat revascularization (HR = 1.15, 95% CI 0.81-1.62, P = .43). Among the 3,001
      patients who did not present with AMI, post-dilation was not associated with
      risks of death/MI (HR = 1.08, 95% CI 0.77-1.50, P = .67) or repeat
      revascularization (HR = 1.17, 95% CI 0.93-1.47, P = .19). Similar effects were
      observed for the restricted analysis with additional adjustment for lesion
      characteristics among the 1,039 AMI patients and 2,179 non-AMI patients with a
      single lesion treated. CONCLUSIONS: Stent post-dilation is associated with an
      increased risk of death/MI in AMI patients but not in non-AMI patients. Further
      investigation is warranted.

PMID- 21095290
TI  - Incidence and natural history of coronary artery aneurysm developing after drug
      eluting stent implantation.
AB  - AIMS: There is a growing concern about the occurrence of coronary artery
      aneurysms (CAAs) after drug-eluting stent (DES) implantation and their long-term
      course. We assessed the occurrence and the factors affecting the long-term
      outcome of DES-associated CAA. METHODS AND RESULTS: We analyzed 3,612 consecutive
      patients (4,419 lesions) who underwent follow-up angiography after DES
      implantation. All 34 CAAs (0.76% per lesion) in 29 patients (0.8% per patient)
      were detected at follow-up, and the mean elapsed time from DES implantation to
      CAA diagnosis was 414 +/- 213 days. Angiographically, CAAs developed almost
      exclusively in complex (type B2/C) de novo lesions (30 [88.2%] of 34 lesions),
      and lesion length was significantly greater in patients with CAA than without CAA
      (26.9 +/- 9.03 vs 23.1 +/- 7.14 mm; P = .004). Myocardial infarction with stent
      thrombosis occurred in 5 patients with CAA (17.2%), 4 of whom were on aspirin
      only without clopidogrel. CONCLUSION: Although CAAs rarely develop after DES
      implantation and show mostly favorable clinical courses, long-term maintenance of
      clopidogrel therapy might be required to minimize occurrence of adverse clinical
      events resulting from stent thrombosis.

PMID- 21095291
TI  - Staged repair of benign tracheo-neo-esophageal fistula 12 years after
      esophagectomy for esophageal cancer.
AB  - Benign tracheo-neo-esophageal fistula is a rare complication after esophagectomy.
      We report a 60-year-old man who presented 12 years after a McKeown esophagectomy
      with a fistula between the tracheal carina and the gastric conduit. In view of
      his severe sepsis and profound malnutrition, he underwent placement of a silicon
      Y-stent with a successful three-stage surgical repair consisting of duodenal
      exclusion with drainage gastrostomy. Six weeks later, the patient had closure of
      the fistula through a right thoracotomy. He finally underwent Roux-en-Y gastro
      jejunostomy through a left thoraco-abdominal approach to restore the
      gastrointestinal continuity. Eighteen months postoperatively, he reports no
      dysphagia and has regained his premorbid weight.

PMID- 21095292
TI  - Desmoplastic small round cell tumor of the lung.
AB  - We report a rare case of desmoplastic small round cell tumor, which arose from
      the left lung. A 25-year-old man was found to have an abnormal shadow during a
      routine physical examination and was admitted to our hospital. A thoracoscopic
      tumor biopsy was performed under general anesthesia. According to the
      histopathologic findings of permanent sections, the tumor was composed of sharply
      outlined nests, clusters, and trabeculae of small round to oval cells separated
      by a spindle-shaped desmoplastic stroma. A gene analysis revealed chimera genes
      of Ewing's sarcoma and Wilms' tumor by reverse transcription polymerase chain
      reaction.

PMID- 21095293
TI  - A complex thoracoabdominal aneurysm in a Loeys-Dietz patient: an open, hybrid,
      anatomic repair.
AB  - We report the successful treatment of a life-threatening thoracoabdominal
      aneurysm in a young patient affected by type I Loeys-Dietz syndrome. To overcome
      anatomic and surgical difficulties, we used an original strategy and a specially
      designed surgical tool. The clinical and technical aspects of this approach are
      presented.

PMID- 21095294
TI  - Surgical treatment of ruptured aneurysm of the left sinus of Valsalva caused by
      Takayasu arteritis.
AB  - Takayasu arteritis is a chronic large-vessel vasculitis that is more frequently
      observed in young women. We report the case of a 29-year-old woman who required
      an operation for an aneurysm of the left sinus of Valsalva that ruptured into the
      left ventricle, for aortic regurgitation, and for left main coronary trunk
      stenosis. The patient had not been previously diagnosed with Takayasu arteritis.

PMID- 21095295
TI  - Repair for mitral stenosis due to pannus formation after Duran ring annuloplasty.
AB  - Mitral stenosis after mitral repair with using an annuloplasty ring is not common
      and it is almost always due to pannus formation. Mitral valve replacement was
      required in most of the previous cases of pannus covering the mitral valve
      leaflet, which could not be stripped off without damaging the valve leaflets. In
      two cases, we removed the previous annuloplasty ring and pannus without leaflet
      injury, and we successfully repaired the mitral valve. During the follow-up of 4
      months and 39 months respectively, we observed improvement of the patients'
      symptoms and good valvular function. Redo mitral repair may be a possible method
      for treating mitral stenosis due to pannus formation after ring annuloplasty.

PMID- 21095296
TI  - Symptomatic compression of the pulmonary artery by a posterior mediastinal
      bronchogenic cyst.

PMID- 21095297
TI  - Cavernous hemangioma of the posterior mediastinum.

PMID- 21095298
TI  - Correction of a severe pouter pigeon breast by triple sternal osteotomy with a
      novel titanium rib bridge fixation.
AB  - We describe a technique of correction of a severe pouter pigeon breast. Three
      osteotomies were performed on the sternum, one resecting the curved fused angle
      of Louis. Multiples chondrotomies allowed to flatten the cartilage part. The
      reconstruction was firmly hardened with a STRATOS titanium device. The cosmetic
      result was satisfactory.

PMID- 21095299
TI  - Early and late clinical outcomes of pulmonary embolectomy for acute massive
      pulmonary embolism.
AB  - BACKGROUND: The aim of this study was to investigate the early and late outcomes
      of patients undergoing pulmonary embolectomy for acute massive pulmonary embolus.
      METHODS: Twenty-one patients (15 male, 6 female) underwent pulmonary embolectomy
      at our institution between March 2001 and July 2010. The median age was 55 years
      (range, 24 to 70 years). Of these, 9 patients presented with out-of-hospital
      cardiac arrest and 8 presented with New York Heart Association class III or IV.
      Sixteen patients underwent preoperative transthoracic echocardiography, which
      showed evidence of right ventricular dilatation in all, whereas in 14 patients
      (66.6%) pulmonary artery pressures were significantly elevated with moderate to
      severe tricuspid regurgitation. The median preoperative Euroscore was 9 (range, 3
      to 16), and 11 patients (52.1%) received systemic thrombolysis preoperatively.
      There were 6 salvage (28.5%), 10 emergency (47.6%), and 5 urgent (23.8%)
      procedures. Concomitant procedures were performed in 3 patients (14.2%), and
      surgery was performed without the use of cardiopulmonary bypass in 3 patients
      (14.2%). The median follow-up was 38 months (range, 0 to 114 months). RESULTS:
      The in-hospital mortality was 19% (n = 4). Postoperative complications included
      stroke (n = 3, 14.2%), lower respiratory tract infection (n = 6, 28.5%), wound
      infection (n = 3, 14.2%), acute renal failure requiring hemofiltration (n = 4,
      19%), and supraventricular tachyarrhythmias (n = 4, 19%). At discharge,
      transthoracic echocardiography showed mild to moderate right ventricular
      dysfunction and dilatation in 11 survivors (64.7%). Two patients died during
      follow-up, and actuarial survival at 5 years was 76.9% +/- 10.1% and at 8 years
      was 51.2% +/- 22.0%. At final follow-up, 11 of the 15 survivors (73.3%) were New
      York Heart Association class I, and no patients required further intervention.
      CONCLUSIONS: Patients who undergo surgery for massive pulmonary embolism have an
      acceptable outcome despite being high-risk.

PMID- 21095300
TI  - Invited commentary.

PMID- 21095301
TI  - Mediastinoscopy in patients with lung cancer and negative endobronchial
      ultrasound guided needle aspiration.
AB  - BACKGROUND: Endobronchial ultrasound with transbronchial needle aspiration (EBUS
      TBNA) has been proposed as a safe, less-invasive alternative to mediastinoscopy
      to stage mediastinal lymph nodes in patients with lung cancer. We evaluated the
      negative predictive value of EBUS-TBNA in lung cancer patients suspected of
      having N2 nodal metastases. METHODS: This study is a single-institution
      retrospective review of cases with suspected or confirmed lung cancer undergoing
      mediastinoscopy after a negative EBUS-TBNA between June 2006 and February 2008.
      RESULTS: A total of 494 patients underwent EBUS-TBNA during the study period.
      Twenty-nine patients with suspected or confirmed lung cancer had a negative EBUS
      TBNA and underwent subsequent mediastinoscopy. Mediastinoscopy was performed for
      findings suspicious of N2 disease based on noninvasive imaging. Mediastinoscopy
      found metastatic nodes in eight of 29 patients (28%) for a patient-specific
      negative predictive value of EBUS-TBNA of 72% (95% CI, 56% to 89%). Mediastinal
      lymph node dissection found four further patients with positive N2 nodes (19%).
      The EBUS-TBNA and mediastinoscopy sampled the same lymph node station on 36
      occasions in the 29 patients. The average lymph node size was 10 mm.
      Mediastinoscopy was positive in 5 of 36 stations, for a nodal-specific negative
      predictive value of EBUS-TBNA of 86% (95% CI, 75% to 97%). CONCLUSIONS:
      Endobronchial ultrasound with transbronchial needle aspiration can effectively
      sample mediastinal lymph node stations in patients with lung cancer. However, in
      this early experience, 28% of patients with high clinical suspicion of nodal
      disease had N2 mediastinal nodal metastases confirmed by mediastinoscopy despite
      negative EBUS-TBNA.

PMID- 21095302
TI  - Invited commentary.

PMID- 21095303
TI  - Computed tomography-guided preoperative radiotracer localization of nonpalpable
      lung nodules.
AB  - BACKGROUND: We describe preoperative computed tomography (CT)-guided injection of
      radiotracer technetium (99m) macroaggregates ((99m)Tc-MAA) in challenging small
      lung nodules, intraoperative localization, and resection. METHODS: Between
      November 2007 and February 2010, 44 patients with 47 lung nodules which were
      detected incidentally or at screening and that were (18)F-fluorodeoxyglucose
      positron emission tomography ((18)F FDG-PET) positive or increasing in size at
      subsequent CT scans were candidates for surgical biopsy. Inclusion criteria for
      preoperative percutaneous CT-guided (low-dose technique) (99m)Tc-MAA localization
      included having at least one of the following characteristics: nodule size less
      than 1 cm, subsolid morphology, or distance from the pleura greater than 1 cm.
      RESULTS: Mean nodule size was 11 mm (range, 5 to 24 mm); 24 nodules were
      nonsolid, 15 nodules were partially solid, and 8 nodules had a solid morphology.
      Mean distance from the pleura was 11 mm (range, 0 to 35 mm). Localization
      complications included 13 minor asymptomatic pneumothoraces, 9 parenchymal
      hemorrhage suffusions, 1 mild allergic reaction to contrast medium, and 2
      patients with chest pain after the procedure. Nine patients had mild
      extravasation of radiotracer into the pleura. In 2 cases, there was an
      extravasation of a significant quantity of radiotracer into the pleural cavity.
      Thoracoscopic biopsy was performed in 30 cases, 2 cases were converted to
      thoracotomy, and 12 patients underwent intentional thoracotomy. CONCLUSIONS:
      Asymptomatic subjects with suspicious nodules detected by screening or incidental
      CT are best candidates due to small lesion size and high percentage of nonsolid
      morphology, making thoracoscopic biopsy potentially difficult. Radiotracer
      localization is a safe, versatile, simple technique to help perform diagnosis
      with a minimally invasive approach in nonpalpable lung lesions.

PMID- 21095304
TI  - Invited commentary.

PMID- 21095305
TI  - Resection of solitary pulmonary lesion is beneficial to patients with a history
      of malignancy.
AB  - BACKGROUND: Solitary pulmonary lesion poses a diagnostic challenge, especially in
      patients with a history of malignancy. The purpose of this study was to evaluate
      the characteristics of solitary pulmonary lesions and the outcome of surgical
      resection. METHODS: We retrospectively analyzed 243 patients with a history of
      cancer who underwent surgery for new-found solitary pulmonary lesion between
      January 1998 and December 2007. RESULTS: The diagnosis was primary lung cancer in
      92 patients, metastasis in 133, and benign lesions in 18. The 5-year survival
      rate was 67.9% in all patients, 74.6% in those with primary lung cancer, 62.8% in
      those with metastasis, and 79.9% in those with benign lesions (p = 0.56). In
      metastasis patients, history of extrapulmonary recurrence and larger diameter
      lesion were risk factors for recurrence by multivariate analysis. History of
      cancers other than colorectal and bone and soft tissue sarcoma and shorter
      disease-free interval were indicators of poor prognosis. Pathologic stage was the
      only indicator of prognosis for primary lung cancer, and none of the factors
      concerning antecedent cancer influenced prognosis. CONCLUSIONS: Surgical
      resection of solitary pulmonary lesion is essential in patients with a history of
      cancer because substantial numbers of benign lesions are included. In the case of
      malignancy, metastasectomy had a life-prolonging effect for selected patients,
      and prognosis of primary lung cancer was no worse than for the general population
      if treated appropriately. It is important not to hesitate to take a surgical
      approach for a diagnosis and to treat with standard therapy for primary lung
      cancer.

PMID- 21095306
TI  - Invited commentary.

PMID- 21095307
TI  - Lung cancer invading the pericardium: quantum of lymph nodes.
AB  - BACKGROUND: Lung cancer may invade the pericardium (T3) and the intrapericardial
      pulmonary veins and left atrium (T4). Our purpose was to analyze the
      characteristics of this invading process in search of the reasons explaining its
      poor prognosis. METHODS: The clinical records of 4,668 patients who underwent
      surgery for lung cancer between January 1983 and December 2006 in two thoracic
      surgery centers were retrospectively reviewed. The epidemiology, pathology, and
      prognostic characteristics of the tumors invading the pericardium alone (T3) or
      with pulmonary veins and atrium (T4) were analyzed and compared with all other
      tumors. RESULTS: There were 75 male and 16 female patients, with 85
      pneumonectomies and 6 lobectomies that proved R0 in 59.3% of patients, and
      contained 69 squamous cell cancers, 11 adenocarcinomas, and 13 miscellaneous
      tumors; 12 were N0 (13.2%), 31 were N1 (34.1%), and 48 were N2 (52.8%).
      Pericardium alone was invaded in 32 patients (35.2%), and with pulmonary vein and
      atrium in 34 (37.3%) and 25 (27.5%), respectively. Patient characteristics were
      similar in each group. Five-year and 10-year survival rates were 15.1% and 10.4%,
      respectively. Frequency of pneumonectomy, R1-2 resection, and N1-2 involvement
      were significantly more important compared with noninvading tumors (p < 10(-6)).
      CONCLUSIONS: Reports on T3 and T4 cancer with pericardial involvement are few,
      but also stress that pulmonary vein and left atrium invasion does not worsen the
      prognosis more than pericardial invasion alone. The rich pericardial lymph
      drainage might enhance the spread of tumor cells, explaining excessively high N1
      N2 rates and pericardial invasion-related poor prognosis.

PMID- 21095308
TI  - Invited commentary.

PMID- 21095309
TI  - Surgical sealant for the prevention of prolonged air leak after lung resection:
      meta-analysis.
AB  - BACKGROUND: We performed a systematic and meta-analysis of randomized controlled
      trials comparing a surgical sealant with buttressed staple lines using standard
      methods. The aim of our meta-analysis was to determine the effectiveness and
      safety of different techniques to reduce the proportion of patients with
      prolonged air leakage after pulmonary resection. METHODS: We searched the
      Medline, Embase, Science Direct, Food and Drug Administration, Cochrane
      controlled trials register, and clinical trial databases for publications between
      January 1995 and May 2009 that included terms related to prolonged air leak after
      lung resection. We included randomized controlled trials comparing glue or patch
      or buttressed staple line with suture or staple in patients undergoing lung
      resection (wedge resection or lobectomy). The prespecified primary outcome of our
      meta-analysis was prolonged air leak more than 7 days. Secondary outcomes were
      the occurrence of adverse effects. RESULTS: Thirteen trials were included in the
      meta-analysis. Overall, the trials had allocated 1,335 patients to glue or patch
      (1,064 patients) or buttress (271 patients) for the prevention of prolonged air
      leak after lung resection. The type of buttress used to reinforce the staple line
      was bovine pericardial strips (271 patients). In the control group of all trials
      for air-leakage management, single or continuous running sutures or staples were
      used according to the routine of the center. The use of glue or a patch or
      buttressing compared with control groups (1,335 patients) decreased prolonged air
      leak more than 7 days. Indeed, the pooled effect size odds ratio was 0.55 (95%
      confidence interval: 0.386 to 0.79). An I(2) of 0% indicated low between-trial
      heterogeneity. The funnel-plot asymmetry coefficient was significantly different
      from zero (asymmetry coefficient -1.23 (95% confidence interval: -2.38 to -0.086;
      p < 0.04), indicating the presence of publication bias. Neither glue nor a patch
      nor buttressing influenced the occurrence of postoperative complications such as
      atelectasis, hemothorax, pneumonia, pneumothorax, and mortality. Eight trials
      (1,020 patients) showed that, compared with control groups, the use of glue or a
      patch or buttressing decreased postoperative arrhythmia, which yielded a pooled
      odds ratio of 0.44 (95% confidence interval: 0.275 to 0.72). CONCLUSIONS: The use
      of surgical sealants and buttressing decreased the risk of prolonged air leakage
      and postoperative arrhythmia after pulmonary resection. However, given the
      possibility of publication bias, the conclusions should be interpreted with
      caution.

PMID- 21095310
TI  - Invited commentary.

PMID- 21095311
TI  - Comparison of outcomes from smoking and nonsmoking donors: thirteen-year
      experience.
AB  - BACKGROUND: Lung transplantation remains the best treatment option for a variety
      of end-stage lung diseases. Pressure on the limited donor pool has led to the use
      of extended criteria donors. One aspect of this has been the liberalization of
      the use of smoking donors (SmD). METHODS: This study is a retrospective review of
      lung transplants performed between April 1995 and August 2008 at a single
      institute. We examined the impact of donor smoking on short-term and long-term
      survival in relationship to recipient and donor demographics such as ischemic
      time, cytomegalovirus status, rates of rejection and infection, ventilation, and
      intensive care stay. Endpoints were survival, infection, and rejection. RESULTS:
      During this 13-year period, 454 lung transplants were performed. Smoking history
      was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one
      patients died within 3 months of transplant leaving 353 alive at 3 months
      posttransplant. Fatalities within the first 3 months were significantly higher in
      the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No
      significant difference in rejection and infection rates between recipients of
      lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51
      and 0.09) was found. Although recipients of lungs from SmD had higher odds of
      ventilation for more than 10 hours, the odds were only increased by 20%, which
      was not statistically significant. Recipients from SmD had significantly longer
      stays in the intensive care (odds ratio 1.9, p = 0.002). There was little
      evidence for an effect of SmD on the development of bronchiolitis obliterans.
      CONCLUSIONS: In this large cohort of patients, donor smoking history has an
      effect on early survival but no effect on long-term survival. The cause of this
      early mortality is independent of infection and rejection. However, these data
      suggest that overall outcomes from the use of donor lungs from smokers are
      acceptable, particularly in the current era with limited donor organs.

PMID- 21095312
TI  - Tracheal replacement with a bioabsorbable scaffold in sheep.
AB  - BACKGROUND: A significant native tracheal approximation phenomenon was observed
      in our previous study [Tsukada H, Ernst A, Gangadharan S, et al. Tracheal
      replacement with a silicone-stented fresh aortic allograft in sheep. Ann Thorac
      Surg 2010;89:253-8], in which sheep trachea was replaced with an allogenic aortic
      graft in order to attempt transplantation. Because an appropriate tracheal
      replacement graft has yet to be determined, other means to repair or replace
      tracheal tissue have to be evaluated. The aim of this study was to test a
      bioabsorbable scaffold for temporary tracheal grafting. METHODS: Eight male sheep
      underwent cervical tracheal replacement (5 cm) using a copolymer of L-lactide and
      epsilon-caprolactone sponge tube reinforced by polyglycolic acid. A silicone
      stent (7 cm) was placed perioperatively to prevent graft collapse. Routine
      bronchoscopy and computed tomographic scans were scheduled for up to 9 months and
      necropsies with histologic examinations were scheduled at 9 months (n = 3), 6
      months (n = 2), 4 months (n = 1), 3 months (n = 1), and 2 months (n = 1) after
      surgery. RESULTS: No procedural deaths and postoperative complications occurred.
      Planned follow-up points were reached in all animals. Computed tomographic
      imaging of the grafted area showed tracheal approximation up to 75% at 9 months
      after surgery. Silicone stents were removed at 9 months in three animals.
      Symptomatic airway collapse was observed at 6 hours, 1 week, and 2 weeks after
      stent removal. Epithelialization of the entire grafted area was confirmed in all
      sheep that were followed beyond 4 months. CONCLUSIONS: Tracheal axial
      approximation occurs consistently after tracheal resection and replacement. Our
      data suggest that bioabsorbable materials can be used as a reliable, temporary,
      tracheal replacement conduit.

PMID- 21095313
TI  - Invited commentary.

PMID- 21095314
TI  - The use of human acellular dermal matrix for chest wall reconstruction.
AB  - BACKGROUND: Reconstruction of chest wall defects has evolved, but challenges
      remain. This is particularly true when defects are large or contamination is
      present. Although numerous materials are available for reconstruction, acellular
      dermal matrix has the advantage of becoming vascularized and incorporated
      autologously. By its resistance to infection and lack of adhesion formation, it
      is a promising although expensive alternative to synthetic materials in some
      circumstances. This report examines our experience with human acellular dermal
      matrix (HADM) in reconstruction of major chest wall and diaphragmatic defects.
      METHODS: A retrospective study was conducted of all patients who underwent
      thoracic reconstruction using HADM between March 2007 and March 2010 at Harbor
      University of California-Los Angeles Medical Center. Data acquisition included
      demographics, surgical indications, operative details, complications, and follow
      up evaluation. RESULTS: Ten patients were identified. Indications included
      thoracic tumor resection in 5, Clagett procedure modification for
      postpneumonectomy empyema in 2, resection of chest wall osteomyelitis in 2, and
      pneumonectomy for multiple aspergillomata in 1. Complications occurred in 4
      patients and included respiratory failure, pneumonia, and wound seromas. All
      wounds healed without need to remove or revise the HADM, and sound chest wall
      closure was achieved in every case. CONCLUSIONS: HADM is an effective but
      expensive alternative to synthetic mesh in reconstruction of chest wall and
      diaphragmatic defects. It is particularly attractive for use under conditions of
      potential or overt contamination.

PMID- 21095315
TI  - Predictors of cervical and recurrent laryngeal lymph node metastases from
      esophageal cancer.
AB  - BACKGROUND: Although patients with esophageal cancer (EC) often develop lymph
      node metastases in the cervical and recurrent laryngeal (CRL) distribution,
      lymphadenectomy in this field is rarely performed. The purpose of this study was
      to determine factors associated with CRL node positivity and to determine the
      appropriate indications to perform a "three field" lymphadenectomy. METHODS: In a
      retrospective review, EC patients who underwent three-field lymphadenectomy were
      analyzed. Predictors of positive CRL nodes were examined univariately, then
      selected for inclusion in a multivariate logistic regression model. RESULTS: From
      1994 to 2009, 185 patients had a three-field lymphadenectomy, of whom 46 patients
      (24.9%) had positive CRL nodes. Final pathology stages (seventh edition) were I
      in 24 patients, II in 43, III in 109, and IV in 1 patient. Eight patients had a
      major pathologic response after induction therapy. On univariate analysis,
      variables significantly associated with positive CRL nodes included squamous cell
      histology, proximal location, advanced clinical presentation, the presence of
      clinical nodal disease, higher pT classification, and higher pN classification.
      There was no reduction in the rate of positive CRL nodes after induction
      chemotherapy. On multivariate analysis, higher pN classification (adjusted odds
      ratio 16.25, 95% confidence interval: 5.40 to 48.87; p < 0.0001) and squamous
      histology (adjusted odds ratio 6.04, 95% confidence interval: 2.21 to 16.56; p <
      0.0001) predicted positive CRL nodes. CONCLUSIONS: Complete lymphadenectomy is
      necessary in esophageal cancer to appropriately stage patients. Low rates of
      positive CRL nodes are present with early clinical stage, with pT0-2 tumors, and
      with pN0 classification, particularly in patients with adenocarcinoma and
      gastroesophageal junction tumors. Dissection of the CRL field should be
      considered with advanced disease for adenocarcinoma and in all patients with
      squamous cell cancer.

PMID- 21095316
TI  - Richard E. Clark Award. Aortic dissection as a complication of cardiac surgery:
      report from the Society of Thoracic Surgeons database.
AB  - BACKGROUND: Aortic dissection as a complication of cardiac surgery is a rare but
      often lethal event. We sought to determine the frequency of this complication in
      the STS (Society of Thoracic Surgeons) database as well as the outcomes of
      patients who suffer intraoperative aortic dissection. We then developed a model
      to identify preoperative characteristics and intraoperative factors associated
      with the complication. METHODS: All patients from the STS database who underwent
      coronary artery bypass grafting, aortic valve surgery, or mitral valve surgery
      were included. Exclusion criteria included any patient who had aortic dissection
      listed as a reason for urgent or emergent operation. Data collected were then
      analyzed to describe the frequency of aortic dissection as a complication as well
      as its consequences. We then analyzed a more recent era that included information
      on arterial cannulation site (femoral-other versus aortic) to identify risk
      factors for aortic dissection. RESULTS: Of 2,219,991 patients analyzed, 1,294
      suffered aortic dissection as a complication of their surgery, for an incidence
      of 0.06%. This complication frequently led to catastrophic results, with 615 of
      1,294 (48%) operative mortality. A logistic regression model was created based on
      2004 to 2007 STS data. Of 680,025 patients analyzed, 436 patients suffered an
      aortic dissection. The analysis yielded nine significant risk factors including
      femoral arterial cannulation, preoperative steroids, and Asian race; the presence
      of diabetes appeared to be protective. CONCLUSIONS: Aortic dissection is a rare
      but catastrophic complication of cardiac surgery. Femoral cannulation is
      associated with an increased frequency of this complication.

PMID- 21095317
TI  - Patient-specific insulin-resistance-guided infusion improves glycemic control in
      cardiac surgery.
AB  - BACKGROUND: Maintenance of appropriate capillary blood glucose in cardiovascular
      surgery patients has been associated with improved outcomes, including lower
      mortality. Interpatient variability in insulin resistance can make management
      difficult, leading to unexpected episodes of hypoglycemia and hyperglycemia. To
      improve postoperative glucose control at our institution, a patient-specific
      insulin-resistance-guided (IRG) protocol was developed. METHODS: Prospective data
      were gathered on 100 consecutive cardiovascular surgery patients managed with our
      standard insulin infusion protocol and 100 patients managed using the IRG
      protocol. Clinical characteristics and glycemic indices were analyzed for the two
      groups. Primary endpoints included (1) percentage of time spent in the target
      range, (2) number of hypoglycemic and hyperglycemic episodes, (3) time to
      achievement of target blood glucose, and (4) the total daily dose of insulin
      required. RESULTS: The IRG protocol resulted in significant improvements,
      including increased percentage of time spent in the normoglycemic range (82.5%
      versus 65.8%, p < 0.001), reduced rate of hypoglycemic episodes (0.12 versus
      0.99, p < 0.01), reduced rate of hyperglycemic episodes (capillary blood glucose
      >126 mg/dL: 4.8 versus 8.2, p < 0.01), and a reduced time to the first
      measurement in the target range. Total daily dose of insulin was mildly
      increased, but failed to reach statistical significance (92.48 versus 82.64
      units, p = 0.32). CONCLUSIONS: Use of the IRG protocol led to improved glycemic
      indices while reducing episodes of hypoglycemia in both diabetic and nondiabetic
      patients. The ability to adjust a patient's insulin dosing based upon factors
      related to their insulin resistance results in improved blood glucose control and
      safety in cardiovascular surgery patients.

PMID- 21095318
TI  - Invited commentary.

PMID- 21095319
TI  - Effects of moderate intensity glycemic control after cardiac surgery.
AB  - BACKGROUND: The impact of intensive insulin therapy on the clinical outcomes of
      hospitalized patients is highly controversial. We used a protocol based on
      dynamic insulin administration targeted to achieve moderately tight glycemic
      control and tested its impact on clinical outcomes after cardiac surgery.
      METHODS: Patients with diabetes mellitus or random blood glucose greater than 150
      mg/dL were treated in the intensive care unit with intravenous insulin, followed
      by a multi-injection protocol consisting of 4 glargine/aspart insulin injections
      in the ward, with a glycemic target of 110 to 150 mg/dL. The study cohort (n =
      410) consisted of consecutive patients undergoing cardiothoracic surgery. Control
      patients (n = 207) were admitted during the first 8 months and treated according
      to standard of care. The intervention group of patients (n = 203) were operated
      on during the following 8 months. The main outcome measures were glycemic control
      and the rate of postsurgery infections. RESULTS: During the intervention, mean
      blood glucose +/- SD was 151 +/- 19 mg/dL and 157 +/- 32 mg/dL in the intensive
      care unit and ward, respectively, versus 166 +/- 27 mg/dL and 184 +/- 46 mg/dL
      during the control period (p < 0.0001). The incidence of hypoglycemia (blood
      glucose less than 60 mg/dL) was low and similar in the two groups (2.5% control
      versus 3% intervention). Intensive insulin treatment decreased the risk for
      infection from 11% to 5% (56% risk reduction, p = 0.018), mainly by reducing the
      incidence of graft harvest site infection (6.9% versus 2.5%, p = 0.034). The
      incidence of atrial fibrillation after coronary artery bypass graft surgery
      decreased from 30% to 18% (39% risk reduction; p = 0.042). CONCLUSIONS: Moderate
      intensity dynamic blood glucose control after cardiac surgery is effective and
      safe, and is associated with improved clinical outcomes.

PMID- 21095320
TI  - Practice patterns for thoracic aneurysms in the stent graft era: health care
      system implications.
AB  - BACKGROUND: The US Food and Drug Administration approved the first thoracic
      aneurysm endograft in 2005. However, because the United States lacks a thoracic
      aneurysm endovascular repair registry, implications of Food and Drug
      Administration endograft approval on surgical management of thoracic aneurysms in
      clinical practice are unknown. METHODS: Retrospective review of thoracic aneurysm
      repair rates for 2000 to 2007 and analysis of patient characteristics and
      complications for 2006 and 2007 cohorts uses the National Inpatient Sample.
      International Classification of Diseases, 9th Revision codes were used to
      identify unruptured descending thoracic aneurysm cases undergoing either thoracic
      endovascular aortic repair (39.73) or open repair (38.45). RESULTS: Thoracic
      aneurysm open repair averaged 3.3 per million from 2000 to 2002 and increased to
      5.6 per million in 2003 with introduction of 16 slice computed tomographic
      scanners. In 2005 endovascular repair was 1.2 repairs per million, which
      increased dramatically to 6.1 repairs per million in 2006. In 2007, endovascular
      repair decreased to 4.8 repairs per million while the open repair rate was 3.1
      repairs per million. The 2006 and 2007 open repair cohorts had more favorable
      baseline characteristics compared with the endovascular cohort. Open repair
      mortality was significantly greater than endovascular mortality in 2006
      (estimated relative risk, 8.48; 95% confidence interval 3.03 to 23.75), but not
      in 2007 (estimated relative risk, 0.71; 95% confidence interval 0.12 to 4.24).
      Length of stay was greater for open repair in 2006 and 2007. CONCLUSIONS:
      Thoracic endovascular aortic repair has been rapidly adopted in the United States
      resulting in increased treatment of thoracic aortic aneurysms. Despite older age
      and comorbidities, endovascular repair had better outcomes and shorter hospital
      stays.

PMID- 21095321
TI  - Invited commentary.

PMID- 21095322
TI  - Operative strategy for descending and thoracoabdominal aneurysm repair with
      preoperative demonstration of the Adamkiewicz artery.
AB  - BACKGROUND: Our study aimed to demonstrate the efficacy of preoperative
      intraarterial computed tomographic angiography to identify the Adamkiewicz artery
      (AKA). We also aimed to investigate the impact of identification of the AKA on
      the strategy for preventing spinal cord injury. METHODS: Thirty-seven patients
      (24 cases of descending aortic aneurysms and 13 cases of thoracoabdominal aortic
      aneurysms), were studied. Average age was 63.8 years old. A pigtail catheter was
      inserted into the descending aorta and its tip was located immediately below the
      left subclavian artery. Subsequently, intraarterial computed tomographic
      angiography was performed and the segmental artery to the AKA was identified.
      Aneurysms were replaced electively with prosthetic graft in all cases. In cases
      where the aortic segment that supplied the AKA was cross-clamped, the identified
      segmental artery-AKA was selectively perfused. In these cases, the segmental
      artery-AKA was reconstructed with an interposition graft. RESULTS: Intraarterial
      computed tomographic angiography successfully identified the segmental artery-AKA
      in all patients. The average number of AKA observed per patient was 1.3+/- 0.6
      AKAs. Selective perfusion of preoperatively identified segmental artery-AKAs was
      performed in 11 cases. The average number of reconstructed segmental arteries was
      0.5 in descending aortic aneurysms and 1.7 in thoracoabdominal aortic aneurysms.
      Although paraparesis occurred in two patients (5%), the remaining 35 patients did
      not suffer spinal cord injury. CONCLUSIONS: Intraarterial computed tomographic
      angiography reliably identifies the segmental-AKA. Furthermore, selective
      perfusion of the segmental artery-AKA, based on accurate preoperative
      identification, might be one option for preventing intraoperative spinal cord
      ischemia.

PMID- 21095323
TI  - Hybrid aortic arch debranching with staged endovascular completion in DeBakey
      type I aortic dissection.
AB  - BACKGROUND: We assess midterm results of a hybrid approach to DeBakey type I
      aortic dissection using a new multibranched Dacron graft to create, by relocation
      of the inflow openings to the arch vessels toward the aortic root, a new aortic
      arch for an easier and safer second-staged endovascular stent grafting of the
      distal thoracic aorta. METHODS: From March 2006 to July 2008 24 patients with
      DeBakey type I aortic dissection underwent ascending aorta and aortic arch
      replacement with debranching of epiaortic vessels using a new prosthesis to
      create an optimal landing zone for possible subsequent endovascular stent
      grafting of the distal thoracic aorta. Fifteen patients, who postoperatively
      presented a residual patent distal false lumen, underwent a successful second
      stage endovascular stent-graft implantation. RESULTS: One patient died after the
      surgical stage while there was no death after the endovascular stage with
      hospital mortality of 4.2%. Follow-up confirmed complete thrombosis of the
      residual distal false lumen in 95.6% and partial thrombosis in 4.4% of patients
      with no evidence of endoleaks in the cases that required the endovascular
      procedure. Overall actuarial survival at 28 months is 92.1% +/- 7.9% with 100%
      freedom from reoperation. CONCLUSIONS: Hybrid treatment of DeBakey type I aortic
      dissection with aortic arch debranching, using a new multibranched prosthesis
      (Lupiae Graft; Vascutek Terumo Inc, Scotland, United Kingdom) is confirmed to
      facilitate the subsequent endovascular completion. Midterm results in terms of
      survival and distal false lumen thrombosis are satisfactory. Further study of
      this operation is warranted to confirm the effectiveness and the durability of
      this approach.

PMID- 21095324
TI  - Invited commentary.

PMID- 21095325
TI  - The early and midterm function of decellularized aortic valve allografts.
AB  - BACKGROUND: This study evaluates the early and midterm results of decellularized
      aortic valve allografts (DAVA) as an aortic valve replacement. METHODS: Between
      October 2005 and February 2010, 41 patients, 28 of whom were male, with a median
      age of 34 years (range, 0.1 to 71), had aortic valve replacement with DAVA.
      Decellularization was obtained with a 0.1% sodium dodecyl sulfate solution.
      Postoperative evaluation was performed with serial echocardiograms, magnetic
      resonance imaging, and multislice computed tomography studies to evaluate valve
      hemodynamics, allograft conduit dimensions, and calcification scores. RESULTS:
      There were 3 early deaths and 1 late death, with a mean follow-up of 19 months
      (range, 1 to 53). There was 1 reoperation due to a failed mitral valve repair. By
      echocardiography in all patients, the median immediate postoperative peak
      gradient was 7 mm Hg (range, 1 to 26 mm Hg), and at last follow-up it was 4 mm Hg
      (range, 1 to 16 mm Hg); valvular regurgitation was graded as none or trivial in
      all but 1 patient, who had a regurgitation graded as mild to moderate. By
      magnetic resonance imaging (n = 4), mean root dimensions were stable at the
      annulus (24 mm), sinus of Valsalva (33 mm), and sinotubular junction (28 mm). By
      computed tomography (n = 22), there was only discrete conduit calcification
      (median calcium score 63 Hounsfield units [HU]; range, 0 to 894 HU) to 3 years of
      follow-up. Conduit biopsy in the patient who underwent reoperation demonstrated
      well-preserved wall structure, absence of calcification, and limited in vivo host
      repopulation. CONCLUSIONS: The early and midterm results with DAVA demonstrated
      stable structural integrity, low rate of calcification, and adequate
      hemodynamics. Although longer periods of observation are necessary, DAVA appears
      to be a promising alternative for aortic valve replacement in selected patients.

PMID- 21095326
TI  - Invited commentary.

PMID- 21095328
TI  - Invited commentary.

PMID- 21095327
TI  - Survival and quality of life after aortic root replacement with homografts in
      acute endocarditis.
AB  - BACKGROUND: Treatment of prosthetic aortic valve endocarditis and native aortic
      valve endocarditis with abscess formation is associated with high mortality and
      morbidity. Aortic root replacement with a freestanding aortic homograft is an
      attractive alternative. We report outcome and quality of life after homograft
      replacement for infective endocarditis. METHODS: Sixty-two patients with
      infective prosthetic valve endocarditis (n = 31) or native valve endocarditis
      with abscess (n = 31), operated with homograft replacement were included. Thirty
      day mortality, severe operative complications (dialysis, stroke, pacemaker
      implantation, myocardial infarction, and prolonged mechanical ventilation),
      midterm survival, reoperations, and quality of life were assessed after a mean
      follow-up of 37 +/- 11 months. RESULTS: Nine patients (15%) died within 30 days
      and 22 patients (35%) had severe perioperative complications. Preoperative and
      perioperative variables univariately associated with early mortality were higher
      (Cleveland Clinic risk score [p = 0.014], extracorporeal circulation time [p =
      0.003], prolonged inotropic support [p = 0.03], reoperation for bleeding [p =
      0.01], and perioperative myocardial infarction [p < 0.001].) Cumulative survival
      was 82%, 78%, 75%, and 67% at one, three, five, and ten years, respectively. One
      patient was reoperated due to recurrence of endocarditis nine months after
      surgery and one after five years due to homograft failure. Quality of life, as
      assessed by the 36 item short-form health survey scales for physical and mental
      health, was not significantly different to an age-matched and gender-matched
      healthy control group. CONCLUSIONS: Severe acute aortic endocarditis treated with
      homograft replacement is still associated with a substantial early complication
      rate and mortality. Long-term survival and quality of life are satisfactory in
      patients surviving the immediate postoperative period.

PMID- 21095329
TI  - Quality of life after aortic root surgery: reimplantation technique versus
      composite replacement.
AB  - BACKGROUND: Recent studies indicate the safety of the aortic valve reimplantation
      technique (David operation) in the long-term follow-up. The aim of this study was
      to compare the results of the David operation with those of the aortic composite
      replacement procedure, with the focus on quality of life (QoL). METHODS: Within a
      6-year period, 143 patients received either an aortic composite replacement
      (composite group, n = 67) or the David-I operation (David group, n = 76). The QoL
      of 108 patients (87% of the living patients) was evaluated postoperatively by the
      36-Item Short Form Health Survey. A subgroup analysis of QoL excluded patients
      with aortic stenosis and type A acute aortic dissection. RESULTS: Hospital
      survival rates (89.6% versus 97.4%, p = 0.102), as well as actuarial 1-year
      survival rate (86.6% versus 91.9%) and 3-year survival rate (81.1% versus 91.9%)
      proved more successful among the David group. Incidences of serious adverse
      events during the follow-up period (10.8% versus 28.3%, p = 0.008) were higher
      for patients of the composite group. The QoL was found to be compromised for
      patients of the composite group, in relation to all criteria outlined in the 36
      Item Short Form Health Survey. Subgroup analysis without patients with dissection
      and aortic stenosis demonstrated a significantly better postoperative QoL for
      patients of the David group. Patients belonging to the composite group were more
      frequently compromised by prosthetic valve noise (p < 0.001). CONCLUSIONS: This
      study demonstrates the superiority of the aortic valve reimplantation compared
      with the aortic composite replacement, regarding both clinical outcome and
      postoperative QoL.

PMID- 21095330
TI  - Clinical outcome of asymptomatic severe aortic stenosis with medical and surgical
      management: importance of STS score at diagnosis.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS) score aims at predicting
      operative mortality in cardiac surgery. The value of this score in predicting
      short- and long-term survival with medical or surgical management in patients
      with asymptomatic severe aortic stenosis (AS) is unknown. METHODS: In a cohort of
      694 patients (aged 71 +/- 11 years) with isolated, asymptomatic severe AS
      (velocity >=4 m/s), STS score was calculated at baseline and its link to survival
      analyzed. Patients were stratified by STS score less than 4%, 4% to 6.5%, and
      6.5% or greater. RESULTS: The STS score showed no association with operative
      mortality within 1 year of diagnosis or any time (1%, 2.9%, and 6.1%,
      respectively, by strata; p = 0.08) and a weak association with 1-year survival (p
      = 0.04). Conversely, long-term survival (10-year) was strongly predicted by STS
      score strata (78%, 47%, and 16%, respectively; p < 0.0001). In multivariate
      analysis, STS score independently predicted mortality (hazard ratio/1%, 1.15
      [1.12 to 1.18], p < 0.0001) or cardiac death (1.21 [1.17 to 1.25], p < 0.0001).
      Aortic valve replacement within 1 year of diagnosis markedly improved survival
      (adjusted hazard ratio, 0.58, p < 0.001). However, benefit of early surgery
      varied according to strata, with no overt benefit with low score (p = 0.83),
      whereas early surgery considerably improved survival in the intermediate strata
      (p < 0.001). CONCLUSIONS: For patients with asymptomatic severe AS, STS score is
      a powerful tool for predicting long-term outcome and for selecting patients
      (particularly those at intermediate risk) who benefit markedly from early
      surgery. Hence, risk-scoring using STS score should be routinely performed in
      patients with AS to support the clinical decision-making process.

PMID- 21095331
TI  - When to operate on the bicuspid valve patient with a modestly dilated ascending
      aorta.
AB  - BACKGROUND: Bicuspid aortic valves (BAV) are frequently associated with
      root/ascending aorta dilatation, but there is controversy regarding when to
      operate to prevent dissection of a dilated aorta associated with a well
      functioning BAV. METHODS: From 1988 through 2008, 158 patients (mean age: 56 +/-
      13.5 years) with a dilated ascending aorta (AA) and a well-functioning BAV were
      referred to our institution. All patients underwent computed tomographic (CT)
      scanning and digitization to calculate mean AA diameter. Forty-two patients
      underwent operation a median of 52 days after initial CT scan with a mean AA
      diameter of 5.6 +/- 0.5 cm. One hundred sixteen patients (mean diameter 4.6 +/-
      0.5 cm) were enrolled in annual or semiannual surveillance. Seventy-one patients,
      45 with 2 or more CT scans, are still under surveillance. RESULTS: Average follow
      up was 6.5 +/- 4.1 years. Overall survival after the first encounter was 93% at 5
      years and 85% at 10 years. A total of 87 of 158 patients had a Bentall or Yacoub
      procedure, with two hospital deaths (2.3%). Mean duration of surveillance in the
      116 patients without immediate operation was 4.2 +/- 2.9 years (481 patient
      years). Average growth rate of the AA in patients with 2 scans or greater was
      0.77 mm/year (p < 0.0001 versus normal population) with no significant impact of
      hypertension, sex, smoking or age. Forty-five of the 116 surveillance patients
      underwent operation after a mean of 3.4 +/- 2.9 years (mean age 55 +/- 14.7
      years; mean AA diameter 4.9 +/- 0.6 cm). Six patients died without surgery,
      median age 82 (range, 44 to 87) years, but none within one year of the last CT
      scan. CONCLUSIONS: A consistent approach to patients with a well-functioning BAV
      and AA dilatation, recommending operation to those with an AA diameter greater
      than 5 cm and deferring operation in patients under surveillance in the absence
      of significant enlargement (>0.5 cm/year), resulted in overall survival
      equivalent to a normal age-matched and sex-matched population. Operation was
      necessary in approximately 10% of patients under surveillance each year.

PMID- 21095332
TI  - Altered oxidative stress responses and increased type I collagen expression in
      bicuspid aortic valve patients.
AB  - BACKGROUND: The mechanisms governing extracellular matrix degradation and smooth
      muscle cell (SMC) loss in the ascending aorta of bicuspid aortic valve (BAV)
      patients are unknown. We recently reported that expression and induction of
      metallothionein, a reactive oxygen species scavenger, is reduced in BAV ascending
      aortic aneurysms relative to nonaneurysmal patients. METHODS: Tissue and primary
      SMCs from patients with and without thoracic aortic aneurysms and metallothionein
      null and wild-type mice were analyzed for cell viability, vascular endothelial
      growth factor (VEGF), and type I collagen gene expression during exposure to
      reactive oxygen species. RESULTS: The BAV SMCs and metallothionein -/- mice
      failed to induce VEGF under conditions of oxidative stress in vitro. Exogenous
      VEGF restored resistance to oxidative stress in BAV SMCs to normal. Type I
      collagen gene induction was increased in BAV aorta. CONCLUSIONS: Lack of VEGF
      induction during exposure to reactive oxygen species suggest that the oxidative
      stress response is faulty upstream of metallothionein and VEGF in BAV SMCs.
      Improvement of cell viability with VEGF treatment suggests that the deficient
      pathway can be rescued by VEGF. Increased type I collagen in BAV suggests that
      lack of metallothionein/VEGF activation in response to reactive oxygen species
      may play a role in extracellular matrix homeostasis of the ascending aorta. These
      data continue to support our hypothesis that BAV SMCs lack sufficient resistance
      to reactive oxygen species to maintain extracellular matrix homeostasis, which
      imparts a predisposition to thoracic aortic aneurysms.

PMID- 21095333
TI  - Dual renin-angiotensin system blockade for patients with prosthesis-patient
      mismatch.
AB  - BACKGROUND: Patients with prosthesis-patient mismatch (PPM) continue to show some
      degrees of left ventricular hypertrophy after aortic valve replacement for aortic
      stenosis. The renin-angiotensin system plays a major role in promoting and
      sustaining hypertrophy. In a controlled, randomized study, we tested the
      hypothesis that the combination of angiotensin-converting enzyme inhibitors
      (ACEi) plus angiotensin II receptor blocker (ARB) can be more effective in
      decreasing hypertrophy than a largely employed association such as ACEi plus beta
      blockers in PPM patients. METHODS: We enrolled a total of 72 patients with aortic
      valve replacement and evidence of PPM (effective orifice area <0.85 cm(2)/m(2))
      at postoperative echocardiography. At discharge, they were randomly assigned to
      ramipril plus candesartan (n = 36) or ramipril plus metoprolol (n = 36). RESULTS:
      At baseline, age, 24-hour blood pressure, left ventricular measurements, and
      transprosthetic gradients were similar between the two groups. After 12 months,
      the extent of 24-hour systolic and diastolic blood pressure decrease was similar
      between the two groups (-13.3% and 16.3% versus -12.3% and 15.8%, respectively; p
      = 0.7 and 0.8, respectively). Left ventricular mass index significantly decreased
      in both groups (ACEi plus ARB 165 +/- 19 g/m(2) to 117 +/- 17 g/m(2); p < 0.0001;
      ACEi plus beta-blockers 161 +/- 15 g/m(2) to 128 +/- 20 g/m(2); p < 0.0001).
      However, patients receiving ACEi plus ARB had a higher decrease of left
      ventricular mass (-46 +/- 15 g/m(2) versus -35 +/- 12 g/m(2); p = 0.001) and a
      lower rate of residual left ventricular hypertrophy (22% versus 47%; p = 0.04).
      CONCLUSIONS: This study shows that in patients with PPM, the association ACEi and
      ARB has a greater antiremodeling effect compared with ACEi and beta-blockers, and
      is independent of blood pressure.

PMID- 21095334
TI  - Predictors of mitral valve repair: clinical and surgeon factors.
AB  - BACKGROUND: Mitral valve repair is acknowledged as desirable and superior to
      replacement for virtually all mitral pathology. Utilizing The Society of Thoracic
      Surgeons (STS) Adult Cardiac Surgery Database (ACSD), a multivariable model was
      created that included patient clinical characteristics and surgeon-specific
      mitral volume to predict the likelihood of mitral valve repair. METHODS: Between
      January 2005 and December 2007, 28,507 patients undergoing isolated mitral valve
      surgery (with or without tricuspid valve surgery, with or without atrial
      fibrillation surgery) by 1,088 surgeons at 639 hospitals in the STS ACSD were
      identified. Patient characteristics independently associated with mitral valve
      repair were identified using a generalized estimating equations logistic
      regression model. Observed mitral valve repair rates were plotted against surgeon
      specific annual mitral volume, and predicted probabilities of mitral repair by
      surgeon volume were calculated after adjusting for patient baseline covariates.
      RESULTS: On average, patients undergoing mitral valve surgery were 62 years old,
      with 51% female and 82% Caucasian. Among surgeons performing mitral procedures,
      the mean rate of mitral valve repair was 41% (range, 0% to 100%) and the median
      number of mitral valve operations per year was 5 (range, 1 to 166). Several
      patient characteristics were independently associated with a decreased odds of
      mitral repair (versus replacement), including mitral stenosis (odds ratio 0.09;
      95% confidence interval: 0.08 to 0.11) and active endocarditis (odds ratio 0.21;
      95% confidence interval: 0.17 to 0.25). While substantial variability in repair
      rates was observed among low-volume surgeons, increased surgeon-level mitral
      volume was independently associated with an increased probability of mitral
      repair. CONCLUSIONS: This analysis demonstrates marked variability in the
      frequency of mitral valve repair, and the influence of both patient- and surgeon
      level factors on the likelihood of mitral valve repair. Increasing surgeon
      specific annual mitral valve volume is associated with a higher probability of
      mitral repair. Identification of these predictors of mitral valve repair creates
      substantial opportunity for quality improvement in patient outcomes in mitral
      valve surgery, potentially through education, adoption of best practices, and
      improved mitral repair enabling technology.

PMID- 21095335
TI  - Clinical and functional effects of restrictive mitral annuloplasty at midterm
      follow-up in heart failure patients.
AB  - BACKGROUND: Restrictive mitral annuloplasty (RMA) is increasingly applied to
      treat functional mitral regurgitation in heart failure patients. Previous studies
      indicated beneficial clinical effects with low recurrence rates. However, the
      underlying pathophysiology is complex and outcome in terms of left ventricular
      function is not well known. We investigated chronic effects of RMA on ventricular
      function in relation to clinical outcome. METHODS: Heart failure patients (n =
      11) with severe mitral regurgitation scheduled for RMA were analyzed at baseline
      (presurgery) and midterm follow-up by invasive pressure-volume loops, using
      conductance catheters. Clinical performance was evaluated by New York Heart
      Association class, quality-of-life-score, and 6-minute hall-walk-test. RESULTS:
      All patients were alive without recurrence of mitral regurgitation at follow-up
      (9.4 +/- 4.1 months). Clinical parameters improved significantly (all p < 0.05).
      Global cardiac function, assessed by cardiac output, stroke volume, and stroke
      work did not change after RMA. Reverse remodeling was demonstrated by decreased
      end-systolic and end-diastolic volumes (16% and 11%, both p < 0.001). Systolic
      function improved, evidenced by increased ejection fraction (0.32 +/- 0.05 to
      0.36 +/- 0.07, p = 0.001) and leftward shift of the end-systolic pressure-volume
      relation (ESV(100): 116 +/- 43 to 74 +/- 26 mL, p < 0.001). Diastolic function,
      however, demonstrated impairment by increased tau (69 +/- 13 to 80 +/- 14 ms, p <
      0.001) and stiffness constant (0.022 +/- 0.022 to 0.031 +/- 0.028 mL(-1), p =
      0.001). CONCLUSIONS: Restrictive mitral annuloplasty significantly improved
      clinical status without recurrence of mitral regurgitation at midterm follow-up
      in patients with heart failure. Hemodynamic analyses demonstrated significant
      reverse remodeling with unchanged global function and improved systolic function,
      but some signs of diastolic impairment. Overall, RMA appears an appropriate
      therapy for patients with dilated cardiomyopathy and functional mitral
      regurgitation.

PMID- 21095336
TI  - Invited commentary.

PMID- 21095337
TI  - Mitral valve morphology assessment: three-dimensional transesophageal
      echocardiography versus computed tomography.
AB  - BACKGROUND: Advances in the minimally invasive mitral valve repair techniques
      increase the demands on accurate and reliable morphologic assessment of the
      mitral valve using three-dimensional imaging modalities. The present study
      compared mitral valve geometry measurements obtained by three-dimensional
      transesophageal echocardiography (TEE) to those obtained with multidetector row
      computed tomography (MDCT) used as a standard reference. METHODS: Clinical
      preoperative MDCT and intraoperative three-dimensional TEE were performed in 43
      patients (mean age 81.0 +/- 7.7 years) considered for transcatheter valve
      implantation procedure. Various measurements of mitral valve geometry were
      obtained from three-dimensional TEE datasets using mitral valve quantification
      software, and compared with those obtained from MDCT images using multiplanar
      reformation planes. RESULTS: Moderate and severe mitral regurgitation was present
      in 48.9% of patients. There was good agreement in mitral valve geometry
      measurements between three-dimensional TEE and MDCT without significant
      overestimation or underestimation and tight 95% limits of agreement. For linear
      dimensions, angles and areas, the 95% limits of agreement were less than 1 cm,
      less than 15 degrees, and less than 2 cm(2), respectively. In addition, the
      intraclass correlation coefficients were more than 0.8 for all parameters.
      Finally, the measurements were highly reproducible, with low intraobserver and
      interobserver variability (nonsignificant overestimation or underestimation and
      narrow 95% limits of agreement). CONCLUSIONS: The present study demonstrates the
      accuracy and clinical feasibility of the assessment of the mitral valve geometry
      with three-dimensional TEE that is comparable to the MDCT measurements. Three
      dimensional TEE and MDCT provide accurate and complementary information in the
      evaluation of patients with mitral valve disease. Its potential incremental
      clinical value in the field of transcatheter mitral repair procedures needs
      further assessment in the future studies.

PMID- 21095338
TI  - Anterior mitral leaflet length: predictor for mitral valve repair in a rheumatic
      population.
AB  - BACKGROUND: The length and mobility of the anterior mitral leaflet (AML) are
      considered important for mitral valve reparability. In this study, we looked at
      AML length as a predictor of mitral valve reparability in a rheumatic population.
      METHODS: Between May and November 2008, 44 patients underwent mitral valve repair
      for pure mitral regurgitation, pure mitral stenosis, and mixed lesions. The mean
      age was 26.5 +/- 10.4 years (range, 9 to 50; median 23.5), and 15 patients were
      less than 20 years old. There were 28 female patients. The mean body surface area
      was 1.37 +/- 0.13 (range, 0.97 to 1.62). In all patients, we measured AML length
      at the A2 segment, both by transesophageal echocardiography and intraoperative
      direct measurement. These measurements were indexed to the body surface area.
      RESULTS: Thirty-five patients had successful repair. Nine patients underwent
      mitral valve replacement after failed repair. The AML lengths were significantly
      higher in the successful repair group as compared with the failed repair group
      (AML length measured by transesophageal echocardiography was 31.4 +/- 4.9 mm
      versus 24.1 +/- 2.2 mm, p = 0.001; AML length measured intraoperatively was 30.8
      +/- 4.4 mm versus 22.3 +/- 1.5 mm, p = 0.001). An intraoperatively measured AML
      length of 26 mm or more predicts reparability with 97.1% sensitivity and 100%
      specificity. Transesophageal echocardiography can reliably judge AML length and
      can also predict reparability. Indexed AML lengths are an even stronger predictor
      of mitral valve reparability, especially in a pediatric population. CONCLUSIONS:
      Indexed AML length is a strong predictor of mitral valve reparability. With a
      value of 18 mm/m(2) or more, repair can be accomplished in all cases.

PMID- 21095339
TI  - Surgical treatment of traumatic tricuspid insufficiency: experience in 13 cases.
AB  - BACKGROUND: Traumatic tricuspid insufficiency (TTI) is uncommon and surgical
      experience is limited. We report our surgical experience with TTI in 13 patients.
      METHODS: From January 2000 through March 2008, we operated on 13 patients with
      TTI (10 men 3 women; mean age, 39.8 +/- 10.5 years). The intervals from trauma to
      diagnosis and from trauma to surgery averaged 37.4 and 54.4 months, respectively.
      At operation, the mechanism of TTI was due to anterior chordal rupture in 8,
      anterior papillary muscle rupture in 3, rupture of anterior papillary muscle and
      chordae in 1, and anterior leaflet defect in 1. In 7 patients the annulus was
      dilated. Valve repair was successful in 13 patients. RESULTS: No early or late
      deaths occurred. Severe hemolysis occurred in 1 patient after tricuspid and
      mitral valve repairs. At follow-up extending to 9.5 years, 9 patients were in New
      York Heart Association functional class I, and 4 were in class II. Transthoracic
      echocardiography demonstrated no or trivial residual regurgitation in 7 patients,
      mild regurgitation in 4, and mild-to-moderate regurgitation in 2. A significant
      decrease of the right ventricular end-diastolic dimension (37.7 +/- 9.7 vs 20.7
      +/- 4.6 mm; p < 0.001) was observed. The mean transvalvular gradient was 2.5 +/-
      0.8 mm Hg. Eleven patients were in sinus rhythm. CONCLUSIONS: Satisfactory early
      and midterm outcomes can be achieved for TTI by tricuspid valve repair. Early
      surgical intervention should be emphasized to achieve good functional results and
      preserve the right ventricular function.

PMID- 21095340
TI  - Cardiac surgery-associated acute kidney injury: a comparison of two consensus
      criteria.
AB  - BACKGROUND: Cardiac surgery-related acute kidney injury has short- and long-term
      impact on patients' risk for further morbidity and mortality. Consensus
      statements have yielded criteria--such as the risk, injury, failure, loss, and
      end-stage kidney disease (RIFLE) criteria, and the Acute Kidney Injury Network
      (AKIN) criteria--to define the type and consequence of acute kidney injury. We
      sought to estimate the ability of both the RIFLE and and AKIN criteria to predict
      the risk of in-hospital mortality in the setting of cardiac surgery. METHODS:
      Data were collected on 25,086 patients undergoing cardiac surgery in Northern New
      England from January 2001 to December 2007, excluding 339 patients on
      preoperative dialysis. The AKIN and RIFLE criteria were used to classify patients
      postoperatively, using the last preoperative and the highest postoperative serum
      creatinine. We compared the diagnostic properties of both criteria, and
      calculated the areas under the receiver operating characteristic curve. RESULTS:
      Acute kidney injury occurred in 30% of patients using the AKIN criteria and in
      31% of patients using the RIFLE criteria. The areas under the receiver operating
      characteristic curve for in-hospital mortality estimated by AKIN and RIFLE
      criteria were 0.79 (95% confidence interval: 0.77 to 0.80) and 0.78 (95%
      confidence interval: 0.76 to 0.80), respectively (p = 0.369). CONCLUSIONS: The
      AKIN and RIFLE criteria are accurate early predictors of mortality. The high
      incidence of cardiac surgery postoperative acute kidney injury should prompt the
      use of either AKIN or RIFLE criteria to identify patients at risk and to
      stimulate institutional measures that target acute kidney injury as a quality
      improvement initiative.

PMID- 21095341
TI  - Invited commentary.

PMID- 21095342
TI  - Bone marrow resident and circulating progenitor cells in patients undergoing
      cardiac surgery.
AB  - BACKGROUND: Vascular trauma induced by surgical revascularization stimulates
      mobilization of hematopoietic and nonhematopoietic progenitor cells. However, it
      is not clear whether mobilized progenitors are functionally active and
      participate in peripheral homing. We have found no clinical studies available
      regarding the reaction of bone marrow to surgical revascularization. METHODS:
      This was an observational prospective study of 76 patients undergoing elective
      coronary artery bypass graft surgery. Bone marrow aspirates and blood samples
      were collected at baseline, at the end of surgery, and 24 hours postoperatively
      (blood samples only). The CD34+, CD34+CD133+, and CD34+CXCR4+ progenitor cell
      counts, CXCR4+ mononuclear cell counts, and CXCR4 expression on CD34+ cells were
      measured by flow cytometry. Progenitor cell functions were studied in vitro by
      clonogenic and migration assays. RESULTS: In response to coronary
      revascularization there was mobilization of CD34+ progenitors, having increased
      migratory and clonogenic function. The CD34+CXCR4+ subsets and CXCR4 expression
      on CD34+ cells in peripheral blood increased significantly 24 hours
      postoperatively. The CXCR4 expression on mobilized progenitors at the end of
      surgery was independently related to baseline CXCR4 expression on bone marrow
      resident CD34+ cells and duration of cardiopulmonary bypass in a multivariate
      model. At the end of surgery there was a significant fall in the expression of
      CXCR4 on CD34+ bone marrow cells, suggesting egress into peripheral circulation
      of the most active CXCR4-expressing progenitors. CONCLUSIONS: Coronary artery
      bypass graft surgery is associated with bone marrow release of functionally
      active progenitor cells. Further studies are needed to verify whether mobilized
      progenitors participate in regeneration of injured tissues.

PMID- 21095343
TI  - Invited commentary.

PMID- 21095344
TI  - Effect of amlodipine in human internal mammary artery and clinical implications.
AB  - BACKGROUND: Graft spasm remains challenging in CABG (coronary artery bypass
      grafting) surgery. We investigated the inhibitory effect of a dihydropyridine
      calcium antagonist amlodipine on the vasoconstriction mediated by potassium
      chloride (KCl), human urotensin-II (hU-II), and U46619 in human internal mammary
      artery (IMA) from patients undergoing CABG. METHODS: Isolated IMA rings (n = 78,
      taken from 42 patients) were studied in organ baths in two ways: the relaxing
      effect of amlodipine on vasoconstrictor-induced precontraction by KCl, hU-II, and
      U46619 and the depressing effect of amlodipine on the contraction. RESULTS:
      Amlodipine caused full relaxation in KCl-contracted (98.0% +/- 2.1%), in hU-II
      contracted (98.5% +/- 2.4%), and in U46619-contracted (96.3% +/- 1.3%) IMA rings
      (n = 8) with 15.5-fold higher potency to KCl than to hU-II (effective
      concentration causing 50% of maximal response [EC(50)]: -8.17 +/- 0.28 vs -6.98
      +/- 0.01 log M, p < 0.001) and 19.5-fold that to U46619 (EC(50): -8.17 +/- 0.28
      vs -6.88 +/- 0.08 log M, p < 0.001). Pretreatment of IMA with plasma
      concentrations of amlodipine (-6.6 log M) significantly depressed subsequent
      contraction to KCl (from 20.8 +/- 2.5 mN to 7.6 +/- 3.0 mN, p = 0.004) and hU-II
      (from 14.1 +/- 4.2 mN to 3.8 +/- 2.0 mN, p = 0.026), but did not significantly
      affect the contraction to U46619. CONCLUSIONS: We conclude that in human IMA
      amlodipine has a potent inhibitory effect on the vasoconstriction mediated by a
      variety of vasoconstrictors. Thus, use of amlodipine in CABG patients is favored
      in treating and preventing graft spasm.

PMID- 21095345
TI  - Invited commentary.

PMID- 21095346
TI  - Late occurrence of atrial arrhythmias after the simple left atrial procedure for
      chronic atrial fibrillation in mitral valve surgery.
AB  - BACKGROUND: We postulated that chronic atrial fibrillation (AF) associated with
      mitral valve disease originated from the distended left atrium and is maintained
      by itself. We had performed a simple left atrial procedure for the elimination of
      chronic AF associated with mitral valve disease in patients from 1993 to 1998.
      This paper evaluated the long-term results of the simple left atrial procedure
      after more than 10 years, and discussed the late occurrence of atrial arrhythmias
      in relation to the left atrial procedure. METHODS: Fifty-two patients were
      examined after the simple left atrial procedure concomitant with mitral valve
      surgery retrospectively. We divided the patients into two groups with or without
      the elimination of AF (AF group and non-AF group). The disappearance of AF was
      estimated by electrocardiography, and atrial function was estimated by
      transthoracic echocardiography. The elimination of chronic AF and the recovery of
      atrial systolic function after surgery were evaluated during more than 10 years
      of follow-up. RESULTS: In a total of 702.5 patient-years of follow-up (range,
      11.3 to 16.1 years; mean, 13.5 +/- 3.5 years), AF disappeared in 73% of the
      patients (38 of 52) at 5 years and in 69% of the patients (36 of 52) at 10 years
      after the simple left atrial procedure. Among the preoperative and intraoperative
      variables, a long duration of AF was the only predictive factor for late
      recurrences of AF (p < 0.05). In the sinus rhythm group, 2 of 36 patients
      remained in left atrial tachycardia. The final success rate in elimination of AF
      and atrial tachycardia was 34 of 52 patients (65.3%) at 10 years. An atrial kick
      was detected in 60% of patients across the mitral valve and in 100% of patients
      across the tricuspid valve by transthoracic echocardiography. CONCLUSIONS: The
      simple left atrial procedure could terminate chronic AF associated with mitral
      valve disease and maintain sinus rhythm for more than 10 years in 65% of chronic
      AF patients. Left atrial tachycardia was a troublesome complication after
      cryoablation toward mitral valvular annulus. This study shows the long-term
      results and problems of the simple left atrial procedure for more than 10 years
      of follow-up.

PMID- 21095347
TI  - Simulation experience enhances medical students' interest in cardiothoracic
      surgery.
AB  - BACKGROUND: Applications to cardiothoracic training programs have declined
      dramatically. Increased effort in recruiting trainees is paramount. In this
      study, we test our hypothesis that mentored instruction on cardiothoracic
      simulators will enhance the interest of junior medical students in cardiothoracic
      surgery. METHODS: First- and second-year medical students were recruited from a
      "surgery interest group" to receive mentored instruction on high-fidelity
      cardiothoracic simulators. Before and after simulation assessment tools were used
      to assess attitudes toward simulation, general surgery, and cardiothoracic
      surgery. RESULTS: Forty-four medical students participated in the study. Although
      80% of the students were interested in pursuing a career in surgery before the
      course, the majority (64%) indicated they were "neutral" about pursuing a career
      in cardiothoracic surgery. After participating in the course, 61% of the students
      agreed or strongly agreed that they were interested in pursuing a career in
      cardiothoracic surgery (p = 0.001). When asked to select a surgical subspecialty
      for their third-year clerkship rotation, 18% of the students selected thoracic
      surgery before participating in the simulator course versus 39% after completing
      the course. This increase was most evident among the female participants, of whom
      only 3 (12%) selected a thoracic rotation before the simulator course versus 9
      (35%) after completion of the course (p < 0.05). CONCLUSIONS: High-fidelity
      surgical simulators are an effective way to introduce medical students to
      cardiothoracic surgery. Participation in moderated simulator sessions improves
      attitudes toward cardiothoracic surgery as a career choice and correlates with a
      greater interest in selecting thoracic surgery as a third-year clerkship
      rotation. The role of surgical simulation as a recruitment tool should be further
      delineated.

PMID- 21095348
TI  - Impact of pump flow rate during selective cerebral perfusion on cerebral
      hemodynamics and metabolism.
AB  - BACKGROUND: Although hypothermic selective cerebral perfusion (SCP) is widely
      used for cerebral protection during aortic surgery, little is known about the
      ideal pump-flow management during this procedure. This study explored cerebral
      hemodynamics and metabolism at two different flow rates. METHODS: Fourteen pigs
      (33 to 38 kg) were cooled on cardiopulmonary bypass to 25 degrees C. After 10
      minutes of hypothermic circulatory arrest, the animals were randomly assigned to
      60 minutes of SCP at two different pump flow rates: 8 mL.kg(-1).min(-1) (n = 7)
      and 18 mL.kg(-1).min(-1) (n = 7). Microspheres were injected at baseline, coolest
      temperature, and at 5, 15, 25, and 60 minutes of SCP to calculate cerebral blood
      flow, cerebral vascular resistance, metabolic rate, and intracranial pressure.
      RESULTS: Cerebral blood flow decreased during cooling to 41% of the baseline
      value (from 57 +/- 10 to 23 +/- 4 mL.min(-1).100 g(-1)). It recovered during the
      initial 15 minutes of SCP, showing a significantly higher increase (p = 0.017) at
      high-flow versus low-flow perfusion (139 +/- 41 versus 75 +/- 22 mL.min(-1).100
      g(-1)). After 60 minutes of SCP the cerebral blood flow almost returned to
      baseline values in the low-flow group (43 +/- 25 mL.min(-1).100 g(-1)), but
      showed an unexpected decrease (30 +/- 7 mL.min(-1).100 g(-1)) in the high-flow
      group. The highest regional cerebral blood flow was seen in the cortex (66 +/- 12
      mL.min(-1).100 g(-1)), followed by the cerebellum (63 +/- 12 mL.min(-1).100 g(
      1)), the pons (51 +/- 17 mL.min(-1).100 g(-1)), and the hippocampus (36 +/- 9
      mL.min(-1).100 g(-1)). Intracranial pressure increased from 11 +/- 3 to 13 +/- 5
      mm Hg during cooling on cardiopulmonary bypass. During low-flow SCP, it stayed
      stable at baseline values, whereas high-flow perfusion resulted in significantly
      higher intracranial pressures (17 +/- 3 mm Hg; p = 0.001). Changes in cerebral
      vascular resistance and metabolic rate showed no significant differences between
      the groups. CONCLUSIONS: High-flow SCP provides no benefit during long-term SCP
      at 25 degrees C. Higher cerebral blood flow during the initial SCP period leads
      to cerebral edema, with no profit in metabolic rate.

PMID- 21095349
TI  - Invited commentary.

PMID- 21095350
TI  - J. Maxwell Chamberlain Memorial Paper for congenital heart surgery. Deep
      hypothermic circulatory arrest does not impair neurodevelopmental outcome in
      school-age children after infant cardiac surgery.
AB  - BACKGROUND: The purpose of this study was to assess deep hypothermic circulatory
      arrest (DHCA) as a modifier of neurodevelopmental (ND) outcomes in preschool
      children after cardiac surgery in infancy for repair of congenital heart defects
      (CHD). METHODS: This is a planned analysis of infants enrolled in a prospective
      study of apolipoprotein E polymorphisms and ND outcome after cardiac surgery. The
      effect of DHCA was assessed in patients with single or biventricular CHD without
      aortic arch obstruction. Neurodevelopmental assessment at 4 years of age included
      cognition, language, attention, impulsivity, executive function, social
      competence, and visual-motor and fine-motor skills. Patient and procedural
      variables were evaluated in univariate and multivariate models. RESULTS:
      Neurodevelopmental testing was completed in 238 of 307 eligible patients (78%).
      Deep hypothermic circulatory arrest was used at the discretion of the surgeon at
      least once in 92 infants (38.6%) with a median cumulative duration of 36 minutes
      (range, 1 to 132 minutes). By univariate analysis, DHCA patients were more likely
      to have single-ventricle CHD (p = 0.013), lower socioeconomic status (p < 0.001),
      a higher incidence of preoperative ventilation (p < 0.001), and were younger and
      smaller at the first surgery (p < 0.001). By multivariate analysis, use of DHCA
      was not predictive of worse performance for any ND outcome. CONCLUSIONS: In this
      cohort of children undergoing repair of CHD in infancy, patients who underwent
      DHCA had risk factors associated with worse ND outcomes. Despite these, use of
      DHCA for repair of single-ventricle and biventricular CHD without aortic arch
      obstruction was not predictive of worse performance for any ND domain tested at 4
      years of age.

PMID- 21095351
TI  - Changes of brain magnetic resonance imaging findings after congenital aortic arch
      anomaly repair using regional cerebral perfusion in neonates and young infants.
AB  - BACKGROUND: The objective of this prospective study is to compare magnetic
      resonance imaging (MRI) findings before and after surgery for repairing
      congenital aortic arch anomalies using regional cerebral perfusion. METHODS:
      Neurologic examinations that included brain MRI, brain sonography, and
      electroencephalograms were performed before and after surgery for congenital
      aortic arch anomalies and the accompanying intracardiac anomalies using regional
      cerebral perfusion in 11 neonates and young infants. RESULTS: The median age at
      operation was 11 days (range, 5 to 46). The diagnoses included coarctation of the
      aorta with accompanying intracardiac anomalies (n = 10) and interruption of the
      aortic arch (n = 1). Aortic arch repair was performed using regional cerebral
      perfusion through the right innominate artery (regional perfusion time: 25.6 +/-
      6.0 minutes) without cardiac arrest. Two patients had new postoperative lesions
      on postoperative brain MRI, and these were acute focal subdural hemorrhage (n =
      1) and acute focal infarction (n = 1). However, they were without clinical
      significance. Periventricular leukomalacia was not observed on brain MRI. There
      was no significant change between the preoperative and postoperative findings on
      brain sonography and electroencephalograms. All the patients showed normal
      neurologic growth for a mean follow-up duration of 175.3 days (range: 25 to 497
      days). CONCLUSIONS: There were newly developed lesions on the postoperative brain
      MRI in 2 of 11 patients, even though these patients showed normal brain
      sonography and electroencephalogram findings and normal neurologic development.
      Our regional cerebral perfusion protocol for aortic arch repair showed tolerable
      neurologic outcomes, and it did not induce periventricular leukomalacia.

PMID- 21095353
TI  - Invited commentary.

PMID- 21095352
TI  - Hypothermic circulatory arrest increases permeability of the blood brain barrier
      in watershed areas.
AB  - BACKGROUND: The integrity of the blood brain barrier (BBB) after cardiopulmonary
      bypass (CPB) with hypothermic circulatory arrest (HCA) is controversial in
      children. We tested the hypothesis that the BBB is disrupted by HCA. METHODS:
      Forty-one piglets (mean weight 11 kg) were randomly allocated to acute and
      survival experiments. Five groups (25 piglets, 5 per group) underwent acute
      studies: anesthesia alone (control); CPB at 37 degrees C with full-flow (FF); CPB
      at 25 degrees C with very low flow (LF); HCA at 15 degrees C, and HCA at 25
      degrees C. Two groups (16 piglets, 8 per group) underwent survival studies: CPB
      at 25 degrees C with LF and HCA. In the acute studies, Evans blue dye (EBD)
      extravasation through the BBB into the brain was measured using two methods: EBD
      absorbance of homogenized brain, and immunohistochemical localization of EBD
      linked albumin for cortex, caudate nucleus, thalamus, hippocampus, and
      cerebellum. In the survival studies, cerebral histology was assessed with
      hematoxylin-eosin stain after sacrifice at 4 days after surgery. RESULTS: The BBB
      disruption was clearly observed around watershed areas for 25 degrees C HCA
      compared with other conditions. Microscopic data showed that leakage of EBD in 25
      degrees C HCA was more severe than control in all brain areas (p < 0.05), and EBD
      and albumin were colocalizing. Histologic damage scores were significantly higher
      in watershed areas with 25 degrees C HCA. CONCLUSIONS: The BBB was impaired
      around watershed areas by 25 degrees C HCA for 1 hour according to both
      macroscopic and microscopic data. An increase in permeability of the BBB may be
      both a sign and a mechanism of brain damage.

PMID- 21095354
TI  - The increasing use of mechanical pulmonary valve replacement over a 40-year
      period.
AB  - BACKGROUND: Because reoperation is often necessary for bioprostheses, mechanical
      pulmonary valve replacement (mPVR) may be appropriate for many patients.
      Mechanical prostheses are durable, but there has been concern concerning valve
      thrombosis and bleeding complications from warfarin. METHODS: Between October
      1965 and August 2008, 54 patients (33 male, median age 30 years, range 5 to 66)
      underwent mechanical PVR at our institution (40 patients since 2004). Forty-nine
      of these 54 patients underwent a total of 110 prior operations (median 2, maximum
      5), including 89 prior operations on the right ventricular outflow tract (median
      1, maximum 4). Diagnoses included congenital (n = 47) and carcinoid (n = 7) heart
      disease. Bleeding complications were compared with a 1:2 matched patient cohort
      (age, gender, and diagnosis) receiving bioprosthetic PVR. RESULTS: The most
      common concomitant procedures were tricuspid valve replacement in 15 patients,
      aortic root replacement in 14, and aortic valve replacement in 13. At last follow
      up in 45 of 51 early survivors (median 2.2 years, maximum 20 years), there was no
      perivalvular leak, vegetations, pannus formation, or valve thrombosis. Further,
      no patient required reoperation on mPVR. Major late bleeding complications
      occurred in 3 of 54 patients in the mPVR group and 4 of 108 in the tissue PVR
      group. CONCLUSIONS: Thromboembolic complications are rare with therapeutic
      international normalized ratios and mechanical PVR provides excellent durability
      and freedom from reoperation. Tissue PVR does not eliminate bleeding
      complications. Mechanical PVR should be considered in select patients with
      multiple prior operations, or when there is another need for warfarin
      anticoagulation.

PMID- 21095355
TI  - Reoperation after supravalvular aortic stenosis repair.
AB  - BACKGROUND: Supravalvular aortic stenosis (SVAS) is the rarest type of left
      ventricular outflow tract obstruction. We reviewed our experience with this
      anomaly and analyzed risk factors for death or reoperation. METHODS: Between 1984
      and 2009, 49 patients had surgery for SVAS. A single-patch technique was used in
      3, two-sinus enlargement in 39, and three-sinus enlargement in 7. Variables
      evaluated included age at surgery (<2 versus >2 years old), presence of pulmonary
      artery stenosis, type of SVAS (focal versus diffuse), presence of valvular aortic
      stenosis, and era of surgery. RESULTS: The only early death occurred in a patient
      who experienced cardiac arrest during anesthesia induction and could not be
      separated from bypass after surgery. There were 2 late deaths at 3 and 11 years
      after SVAS repair, both related to treatment for pulmonary artery stenosis.
      Actuarial survival at 5, 10, and 20 years was 95%, 95%, and 90%, respectively.
      Sixteen patients required 23 reoperations: for pulmonary artery stenosis (n =
      10), distal aortic stenosis (n = 9), aortic valve stenosis (n = 4), and coronary
      artery stenosis (n = 1). Actuarial reoperation-free survivals at 5, 10, and 20
      years were 73%, 58%, and 52%, respectively. Coexistent pulmonary artery stenosis,
      young age at surgery, and diffuse type SVAS were predictors of lower freedom from
      death or reoperation by both univariate and multivariate analyses. CONCLUSIONS:
      Survival after surgical repair of SVAS is excellent. However, reoperation is
      frequent, especially when the patients also have pulmonary artery stenosis,
      diffuse type SVAS, and initial surgery at a young age.

PMID- 21095356
TI  - Do high-risk infants have a poorer outcome from primary repair of coarctation?
      Analysis of 192 infants over 20 years.
AB  - BACKGROUND: Balloon angioplasty for infant coarctation is associated with a high
      recurrence rate, making operative repair the gold standard for low-risk infants.
      Debate exists as to whether high-risk infants might be better served with primary
      angioplasty. We compared the outcome in high-risk versus low-risk infants over 20
      years, in a center that always used surgical repair as the primary intervention.
      METHODS: Of 192 infants from 1986 to 2005, 56 were considered "high-risk,"
      defined as requiring prostaglandin infusion together with either epinephrine
      infusion for 24 hours preoperatively, or ventilation and milrinone infusion for
      24 hours preoperatively. All high-risk patients had a period of ventricular
      dysfunction prior to surgery, ranging from mild to severe. Outcomes were compared
      using Bonferroni comparison of means or the Fischer exact test as appropriate.
      RESULTS: Although the high-risk patients were smaller (3.3 +/- 0.1 vs 4.2 +/- 0.2
      kg, p < 0.01), younger (18 +/- 4 vs 57 +/- 7 days, p < 0.01), and more often
      required a concomitant pulmonary artery band (25% vs 15%, p = 0.05), their cross
      clamp times were the same as the low-risk patients (18.9 +/- 0.9 vs 18.0 +/- 0.4
      minutes, p = 0.27) and there was no difference in postoperative morbidity (7% vs
      3%, p = 0.11). However, there was a trend toward higher perioperative mortality
      (7% vs 2%, p = 0.07). When compared with the published studies of primary
      angioplasty in comparable high-risk infants, the mortality rate in our surgically
      treated high-risk group is much lower. Additionally, only 11% of our high-risk
      group required reintervention, with two-thirds treated successfully with a single
      angioplasty at 3.8 +/- 2.2 years later, far lower than recurrence rates with
      primary angioplasty. CONCLUSIONS: We propose that primary surgical repair of
      coarctation in infants who are high risk should be the primary treatment, with
      angioplasty reserved for recurrent coarctation.

PMID- 21095357
TI  - Simple prophylactic fixation for lung torsion.
AB  - PURPOSE: Although pulmonary torsion is a rare complication after lung resection,
      thoracic surgeons should always consider the risk of this development. We
      describe a new prophylactic method to repair the residual lobe by using an
      absorptive sheet and fibrin glue. DESCRIPTION: Between January 2009 and March
      2010, 6 patients underwent this simple prophylactic fixation for lung torsion,
      and their clinical records were retrospectively reviewed. EVALUATION: No
      postoperative complications were observed in this series. CONCLUSIONS: This
      technique is satisfactorily effective and does not result in any complications.

PMID- 21095358
TI  - Sarcoid-like reaction mimics progression of disease after induction chemotherapy
      for lung cancer.
AB  - The use of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) for
      staging nonsmall cell lung cancer is widely recognized, whereas the value of
      fluorodeoxyglucose-positron emission tomography imaging in the evaluation of
      response to induction chemotherapy is still controversial. We describe a case of
      a 57-year-old man who had a sarcoid-like reaction develop during induction
      chemotherapy for a pathologically proven N2 lung cancer. Re-evaluation of the
      nodal status using fluorodeoxyglucose-positron emission tomography showed false
      positive accumulation in the mediastinal and hilar lymph nodes, which led us to
      suspect lung cancer progression after induction chemotherapy.

PMID- 21095359
TI  - Venous hemangioma presenting as a superior sulcus tumor.
AB  - Non-small cell pulmonary carcinomas represent the majority of tumors located in
      the superior sulcus. However, only 5% of all non-small cell pulmonary carcinomas
      present in the superior sulcus. Other causes of superior sulcus tumors include
      metastatic tumors, hematologic malignancies, infectious causes, and amyloid
      nodules, as well as other lesions. We report a case in which a venous hemangioma
      presented as a superior sulcus tumor.

PMID- 21095360
TI  - Transapical valve implantation after David operation and stenting of the
      descending aorta.
AB  - This case report illustrates our experience with transapical minimally invasive
      aortic valve implantation in a patient with an extended aneurysm of the
      thoracoabdominal aorta, who had previously undergone a replacement of the
      ascending aorta with concomitant aortic valve reconstruction (David procedure).
      Endovascular stent grafting of the descending aorta was also performed. The
      implantation of a 23-mm SAPIEN valve (Edwards Lifesciences, Irvine, CA) did not
      interfere with the existing 26-mm aortic Hemashield prosthesis (Boston
      Scientific, Natick, MA) or the previously implanted endograft in the descending
      aortic position. No paravalvular leakage with aortic valve regurgitation,
      prosthesis instability, or coronary malperfusion was seen after valve
      implementation.

PMID- 21095361
TI  - Unexpected small bowel intussusception caused by lung cancer metastasis on 18F
      fluorodeoxyglucose PET-CT.
AB  - Small bowel metastasis from primary lung cancer is rare. We report the case of an
      unexpected small bowel intussusception caused by primary non-small cell lung
      cancer, which was primarily detected by 18 fluorine ((18)F)-fluorodeoxyglucose
      (FDG) positron emission tomography (PET) and computed tomography (CT). A 74-year
      old man underwent FDG PET-CT for the diagnostic workup of a lung mass in the left
      upper lobe. On FDG PET-CT images, intense FDG uptake was observed in the primary
      lung mass lesion and mediastinal paraesophageal area. Furthermore, unexpected
      intense FDG uptake was observed in the jejunum along with the findings of
      intussusception in the proximal jejunum on the CT images of the PET-CT, which
      suggested jejunojejunal intussusception caused by lung cancer metastasis. The
      patient underwent an immediate operation, and the histopathologic results of the
      resected bowel indicated metastatic lesion from adenocarcinoma of the lung.

PMID- 21095362
TI  - Use of ECMO for resection of post-traumatic ruptured lung abscess with empyema.
AB  - We report a patient who sustained multiple injuries from a motorcycle collision.
      He had a protracted intensive care course complicated by ventilator-associated
      pneumonia and empyema resulting from a ruptured lung abscess. He successfully
      underwent a thoracotomy, lung resection, decortication, and pleurectomy on veno
      venous extracorporeal membrane oxygenation.

PMID- 21095363
TI  - Video-assisted thoracoscopic surgery for a cystic seminoma of the mediastinum.
AB  - Mediastinal seminomas are uncommon primary mediastinal neoplasms, and most are
      solid in appearance. Cystic mediastinal seminoma is an unusual type of
      extragonadal germ cell tumor that has rarely been reported in the literature.
      Here we describe a 36-year-old man with a 7.5-cm cystic mediastinal seminoma. The
      tumor was excised successfully by video-assisted thoracoscopic surgery. No
      recurrence was noted during 28 months of follow-up.

PMID- 21095364
TI  - Arrhythmogenic left ventricular cardiomyopathy associated with noncompaction.
AB  - A 46-year-old woman was admitted to our hospital because of progressive
      exertional dyspnea and occasional premature ventricular contraction. An enhanced
      computed tomographic scan revealed partial defect of the left ventricular
      myocardium and prominent trabecular meshwork at the same thin-wall segment. She
      underwent resection and endoventricular patch plasty using cardiopulmonary
      bypass. Histopathologic examination showed transmural fibro-fatty replacement of
      the myocardium, with an extremely thickened endocardium. Here we report an
      extremely rare case of surgery in a patient with arrhythmogenic left ventricular
      cardiomyopathy associated with left ventricular noncompaction.

PMID- 21095365
TI  - A rare case of coronary artery bypass grafting in a patient with left ventricular
      noncompaction.
AB  - Ventricular myocardium noncompaction is a rare congenital cardiomyopathy
      resulting from an arrest in normal endomyocardial embryogenesis. Initially the
      noncompaction of the left ventricle was described in the pediatrics population
      with poor prognosis, but recent reports have noticed the presence of this
      pathology in the adult population. We describe a 54-year-old man with isolated
      noncompaction of the left ventricle who had ischemic heart disease and was
      successfully treated with bypass surgery.

PMID- 21095366
TI  - Idiopathic pulmonary artery aneurysm with pulmonary regurgitation.
AB  - Idiopathic pulmonary artery aneurysms are rare and need a multidisciplinary
      approach to diagnosis and treatment. Surgery is the treatment of choice,
      especially when the aneurysms are large and when they are associated with
      pulmonary regurgitation. This report highlights a case in which successful
      surgical repair preserved the native pulmonary valve after pulmonary artery
      reconstruction.

PMID- 21095367
TI  - Successful thrombolysis after pulmonary endarterectomy.
AB  - We report the case of a 51-year-old woman who underwent pulmonary endarterectomy
      for chronic thromboembolic pulmonary hypertension. On postoperative day 1 she
      developed bilateral pulmonary thrombosis due to preoperatively undiagnosed
      heparin-induced thrombocytopenia. Systemic thrombolytic therapy with alteplase on
      postoperative days 5 and 6 resulted in marked clinical improvement. To our
      knowledge this is the first report of successful thrombolysis of pulmonary
      thrombosis due to heparin-induced thrombocytopenia after pulmonary
      endarterectomy.

PMID- 21095368
TI  - Occlusion of left coronary ostium with a rudimentary aortic cusp.
AB  - A 74-year-old woman with exertional angina was diagnosed with occlusion of the
      left coronary ostium associated with a rudimentary aortic valve cusp. A
      transesophageal echocardiogram, a multi-detector computed tomographic scan, and a
      coronary angiographic scan revealed the rudimentary aortic cusp covering the
      small left coronary aortic sinus leading to occlusion of the ostium of the left
      coronary artery, despite the intact coronary arteries. After excision of the
      rudimentary left coronary cusp, the left coronary ostium appeared intact. An
      aortic valve replacement with annular enlargement using a bioprosthetic valve was
      performed. The patient uneventfully recovered without angina.

PMID- 21095369
TI  - Absence of posterior mitral leaflet with secundum atrial septal defect.
AB  - A rare case of a 54-year-old woman with absence of congenital posterior mitral
      leaflet, moderate mitral insufficiency, and large secundum-type atrial septal
      defect is reported. Two-dimensional color Doppler and transesophageal
      echocardiography revealed complete absence of the posterior mitral leaflet, a
      thick muscular formation replacing the posterior leaflet, a 3.3-cm secundum type
      atrial septal defect, and severe pulmonary hypertension. This report describes
      the rare case of congenital absence of posterior mitral leaflet associated with
      secundum type large atrial septal defect in a middle-age woman.

PMID- 21095370
TI  - Hybrid procedure for obstructive neonatal left ventricular tumors.
AB  - We report the use of the hybrid procedure (bilateral pulmonary artery banding,
      ductal stenting followed by balloon atrial septostomy) in the first week of life
      for the treatment of two neonates with large left ventricular fibromas resulting
      in univentricular physiology. At 6 months of age, second-stage palliation was
      accomplished and the 2 patients are growing well with normal developmental
      milestones and no atrial or ventricular ectopy at 30 months. Hybrid strategy
      offers a less invasive, initial intervention and the options of typical second
      stage univentricular palliation, conversion to biventricular physiology in cases
      of tumor regression, planned surgical resection, or transplantation.

PMID- 21095371
TI  - Three-dimensional imaging of an anomalous systemic artery supplying normal lung.

PMID- 21095372
TI  - Pneumothorax, pneumomediastinum and hemorrhagic shock complicating oxygen
      administration through a nasopharyngeal catheter.

PMID- 21095373
TI  - Concomitant aortoesophageal and aortobronchial fistula after endovascular aortic
      repair.

PMID- 21095374
TI  - A new application for the heart positioner in operations for mediastinal tumors.
AB  - We applied a heart positioner during operations to remove large mediastinal
      tumors. Fixing and lifting the tumor with this device allowed a good view behind
      the tumor. Separating the tumor from surrounding structures was easy and safe,
      with no risk of insult. The device caused no damage to the tumor capsule. This
      could represent a novel method to remove large mediastinal tumors safely and
      effectively.

PMID- 21095375
TI  - Anterior diaphragmatic plication in mediastinal surgery: the "reefing the
      mainsail" technique.
AB  - Diaphragmatic plication is usually obtained by suturing the entire dome, which
      can be laborious when an anterior approach is used. The same result can be
      obtained by anchoring the redundant diaphragm to the anterior costal arch
      maneuver, which resembles the action of reefing the mainsail on the boom of a
      sailboat. Radiologic results have been analyzed from a series of 10 consecutive
      patients who underwent mediastinal surgery with phrenic nerve section. One week
      after surgery, no patient had an eventrated diaphragm on lateral chest
      roentgenogram. No lower lobe atelectasis was recorded in the series until
      discharge. This technique represents an alternative to classic diaphragmatic
      plication with three main advantages: (1) it does not require suturing of the
      posterior part of the dome, which can be difficult to reach when an anterior
      approach (sternotomy or hemi-clamshell) is used; (2) the presence of three
      sequential steps, which progressively increases diaphragmatic stretching and
      permits adjusting the tension of the dome; and (3) the possibility of standard
      plication is not precluded.

PMID- 21095376
TI  - Combined unilateral-thoracoscopic and mediastinoscopic thymectomy.
AB  - To achieve maximal benefit, after thymic tissue and mediastinal fat were removed
      by thoracoscopic thymectomy, a transverse cervical incision allowed access to
      remove fat in the neck. A mediastinoscopy was then performed for removal of the
      fat in the retrosternal area superior to the innominate vein. In 15 cases,
      ectopic thymic tissue was found. There were three cases in which the residual
      superior horns of thymus were found in the neck and three in the retrosternal
      area. The combined use of a mediastinoscope and a thoracoscope can remove almost
      all the thymus, including ectopic tissues. Long-term results are still being
      awaited.

PMID- 21095377
TI  - A device for ensuring the neochordae replacement in mitral valve repair.
AB  - We have developed a new device for maintaining artificial chordae at the
      appropriate length during the tying of Gore-Tex sutures (W. L. Gore and Assoc,
      Flagstaff, AZ). This double-armed, double-hooked device is inserted through the
      loop formed by the neochordae, which is anchored in the papillary muscle and
      passed through the prolapsing segment. The device pulls up both leaflets and
      maintains the neochordae at the same length as that of the opposing normal
      chordae. The prolapsed leaflet is suspended at the same height as the facing
      leaflet, enabling the accurate and reproducible placement of neochordae.

PMID- 21095378
TI  - Rapid two-stage Starnes procedure for a symptomatic neonate with Ebstein anomaly.
AB  - We present a rapid two-stage Starnes procedure for a seriously symptomatic
      neonate with the prenatal diagnosis of Ebstein anomaly. At 16 hours after birth,
      we performed an emergency operation consisting of main pulmonary artery ligation,
      plication of the right atrial and right ventricular wall, modified Blalock
      Taussig shunt, and patent ductus arteriosus ligation, without cardiopulmonary
      bypass. At age 12 days, we then performed the Starnes procedure using a
      glutaraldehyde-treated autologous pericardial patch with a 4-mm fenestration to
      close the tricuspid valve orifice. The infant's postoperative course was
      excellent. A rapid two-stage Starnes procedure is useful for treating a seriously
      symptomatic neonate with Ebstein anomaly.

PMID- 21095379
TI  - Single ventricle strategy for Uhl's anomaly of the right ventricle.
AB  - Uhl's anomaly is a rare condition and surgical techniques are few and have had
      variable success. We present a novel and successful surgical technique to treat
      this difficult condition.

PMID- 21095380
TI  - Surgical treatment of atrial fibrillation: the time is now.
AB  - Atrial fibrillation (AF) is the most common chronic arrhythmia in the United
      States and is associated with high morbidity rates and significant healthcare
      costs. Although medical therapy for AF modestly reduces complications, cardiac
      surgery continues to have an important role in the treatment of AF and is
      constantly evolving. Cardiothoracic surgeons are uniquely positioned to offer
      effective operations to patients with lone AF, in addition to those undergoing
      concomitant elective cardiac surgery. This review discusses (1) the burden of AF,
      (2) classification and electrophysiology of AF, (3) surgical techniques and
      outcomes, and (4) future directions in surgical therapy.

PMID- 21095381
TI  - Metal allergy, atrial septal occluder devices and the risk of Kounis syndrome.

PMID- 21095382
TI  - A rare complication indeed.

PMID- 21095383
TI  - Preoperative carotid reperfusion in type A aortic dissection: how safe is it?

PMID- 21095385
TI  - Biodegradable ring annuloplasty for acute endocarditis.

PMID- 21095386
TI  - Mitral valve replacement in heavily calcified annulus.

PMID- 21095388
TI  - Tracheal replacement with aortic allografts in the pig.

PMID- 21095390
TI  - [At risk mental status in 15- to 25-year-olds: the 1st episodes].

PMID- 21095391
TI  - Early intervention in psychosis: specialized intervention and early case
      identification.
AB  - Specialized early intervention (SEI) approach to treatment of a First Episode of
      Psychosis (FEP) consists of two equally important components, namely, a phase
      specific treatment program and early case identification. In this article we
      report a brief update on our knowledge about both aspects of SEI services. We
      then provide a description of a prototypical SEI service within the Canadian
      context, examine the pathways to care for patients with FEP and report on
      different methods of reducing delay in treatment. We also provide a description
      of a novel method of reducing delay in treatment using principles of academic
      detailing targeting all health care and educational services within a defined
      catchment area in combination with quick access to the SEI service.

PMID- 21095392
TI  - [Which course of medical care to provide for teenagers with behavioural
      disorders?].
AB  - Teenage claustration and wandering entail specific issues, in connection with the
      diagnosis and the therapy involved, because of the particular relationship of
      these teenagers with time and space. A course of specific coordinated medical
      care (emergency admission, hospitalization, follow-up care) is offered to them as
      well as to their family, according to certain modalities within a department of
      psychiatry for adults.

PMID- 21095393
TI  - [The outcome of pervasive development disorders after the adolescence].
AB  - Until the end of the 20th century, the medical literature was very pessimistic
      concerning the clinical and natural course of autistic spectrum disorders from
      childhood to adulthood. Fortunately, during the last decade, we met dramatic
      turnovers in the domain of pervasive developmental disorders, especially in terms
      of prevalence (now estimated at about 1 % of the population). Besides, for the
      first time, we are now able to build a strong link between recent genetic
      discoveries, the neurophysiopathology of autism and new subsequent therapeutic
      tools.

PMID- 21095394
TI  - [Which cognitive remediation programs are adapted to first episode of
      psychosis?].
AB  - Cognitive remediation is efficient to treat cognitive disorders associated with
      schizophrenia. Since (i) these disorders play a negative role in functional
      outcome and (ii) antipsychotics do not improve significantly cognition, cognitive
      remediation should be systematically used with patients with schizophrenia and
      after the first episode of psychosis. A comprehensive neuropsychological
      assessment, that precedes the beginning of cognitive remediation, allows
      targeting the most impaired cognitive domains. Cognitive remediation intervention
      takes place after symptoms stabilization. It needs also that the antipsychotic
      treatment was prescribed at minimal fully effective dose and that the patients
      have acquired a minimal understanding of their disease (i.e. after
      psychoeducation). Cognitive remediation programs that have been validated for
      schizophrenia (NEAR, CET, NET, IPT, CRT...) can be used after the first episode
      of psychosis.

PMID- 21095395
TI  - [Brain imaging and transition to psychosis].
AB  - First episode psychosis is usually preceded by a prodromal period of about 5
      years during which the manifestation of the disease is not yet clear. This
      prodromal phase is called 'At Risk Mental State' (ARMS) as all subjects with
      prodromal symptoms will not develop a psychotic disorder. Several brain imaging
      studies have been conducted over the past decade in these ARMS subjects and found
      structural, functional and neurochemical deviations. These deviations are similar
      to those observed when the psychosis is established but with less severity. These
      deviations have important translational perspective as they might help to
      distinguish the development of a psychotic disorder from occasional psychotic
      symptoms.

PMID- 21095396
TI  - [First episode of mood disorders: an opportunity for early intervention in
      bipolar disorders].
AB  - While early intervention strategies have been developed for psychotic disorders,
      affective psychoses and bipolar disorders have been neglected by this movement.
      However, when considering that outcome of bipolar disorders is often not as
      favorable as previously thought and that delay between illness onset and
      introduction of an adequate treatment is often very long, such developments seem
      clearly justified. In this paper we briefly review arguments supporting early
      intervention in bipolar disorders, the practical and theoretical obstacles that
      still need to be overcome, the strategies that may already now contribute to
      decrease treatment delay, and we describe current state of research regarding
      identification of the prodromal phase of bipolar disorders.

PMID- 21095397
TI  - Immediately loaded fixed maxillary implant treatment for a patient with advanced
      periodontal disease: a clinical report.
AB  - Patients with a failing maxillary dentition typically require an extended
      treatment sequence that involves extractions, interim prosthesis wear, grafting
      and subsequent implant placement, and restoration with an implant-supported fixed
      or bar-retained prosthesis. Established maxillary implant protocols can take up
      to 15 or more months to complete. The purpose of this report is to describe a
      treatment sequence using zygomatic implants in a patient with advanced
      periodontal disease. A fixed prosthesis was fabricated without grafting,
      resulting in a shortened treatment time.

PMID- 21095398
TI  - Management of a failed mandibular staple implant: a clinical report.
AB  - A 48-year-old woman sought treatment because her staple implant-retained
      overdenture was no longer retentive, and the denture was worn over the abutments.
      After unsuccessfully attempting to move the retentive nuts along the transosseous
      posts of the staple implant, the posts were cut off at the level of the bone. Two
      endosseous implants were placed around the staple implant, and a new implant
      retained overdenture was fabricated and inserted using ball attachments for
      retention. This article describes the treatment for this patient, who has been
      wearing the new dentures successfully for the past 4 years.

PMID- 21095399
TI  - A randomized clinical trial to compare diagnostic casts made using plastic and
      metal trays.
AB  - STATEMENT OF PROBLEM: Virtually every prosthodontic rehabilitation involves
      making diagnostic casts for analysis and prosthesis fabrication. Frequently,
      these casts are produced using irreversible hydrocolloid (IH) impression
      materials in stock metal or plastic trays. However, it is unclear whether one
      technique produces a more accurate cast. PURPOSE: The purpose of this randomized
      clinical trial was to compare the linear accuracy of diagnostic casts produced
      using IH with 1 of 3 different tray types: (1) perforated metal trays, (2) stock
      plastic trays, and (3) directed-flow stock plastic trays. All groups were
      compared to casts produced with custom trays and vinyl polysiloxane (VPS)
      impression materials, which were considered the control. MATERIAL AND METHODS:
      Seven subjects participated in this trial. IH impressions were made in a random
      order using 1 of 3 tray types: stock plastic, perforated metal, or plastic
      directed flow. These were compared to VPS impressions using custom trays (control
      group). Each impression technique was repeated 3 times per subject, for a total
      of 84 observations. Impressions were disinfected and poured in a type IV stone.
      Linear accuracy of casts was measured using computer software analysis of scanned
      images of the casts at x30 magnification. Three linear measurements were made on
      each cast: second molar to second molar, right second molar to left first
      premolar, and left second molar to right first premolar. Measurements were
      compared among techniques using mixed-model analysis of variance to account for
      correlation among the multiple measurements made on each subject. Dunnett's
      adjustment for multiple comparisons with control was used (alpha=.05). RESULTS:
      For molar-to-molar and right second molar to the left first premolar
      measurements, there were no significant differences in linear dimensions between
      casts made from different trays. However, linear measurements from the left
      second molar to the right first premolar demonstrated significant differences for
      casts made with stock metal, directed-flow, and stock plastic trays compared to
      custom trays. In this group, casts produced by stock metal, directed-flow, and
      stock plastic trays differed from controls by 102, 68, and 71 um, respectively.
      Generally, casts made with plastic trays (stock plastic and directed flow) had
      values closer to those of custom trays than did casts made with metal trays.
      CONCLUSIONS: Impressions made with irreversible hydrocolloid produced casts that
      were significantly different in linear dimension than casts produced by custom
      trays and VPS impressions. These differences were not uniform, but varied by
      location on the cast.

PMID- 21095400
TI  - The effect of repeated firings on the color of an alumina ceramic system with two
      different veneering porcelain shades.
AB  - STATEMENT OF PROBLEM: Possible sources of processing variables in porcelain
      firing include thickness and color of the opaque; thickness, color, and
      translucency of the body and enamel layers; firing temperature; and number of
      firings. PURPOSE: The purpose of this in vitro study was to investigate the color
      changes of an alumina ceramic system veneered with different veneering porcelain
      shades and fired different numbers of times. MATERIAL AND METHODS: Twenty disc
      shaped ceramic specimens (10 mm in diameter, with a core thickness of 1 mm), with
      2 different veneering porcelain shades (A1, A3), were fabricated from an alumina
      ceramic system (Turkom-Cera) (n=10). Repeated firings (3, 5, 7, or 9 firings)
      were performed, and color differences (DeltaE) were determined using a
      spectrophotometer. Repeated-measures ANOVA was used to analyze the data (number
      of firings, veneering porcelain color). The Duncan test and paired 2-tailed tests
      were used for multiple comparisons (alpha=.05). RESULTS: The L*a*b* values of the
      ceramic system were affected by the number of firings (3, 5, 7, or 9) (P<.005)
      and veneering porcelain shade (P<.001). Significant interactions were present
      between the number of firings and the veneering porcelain shade for L* (P=.002),
      a* (P=.001), and b* (P=.001) values. A1 shade specimens maintained their L* value
      independent of the number of firings, whereas A3 shade specimens became lighter
      after an increased number of firings. For both A1 and A3 veneering porcelain
      shades, the a* value decreased after repeated firings, which resulted in less
      reddish specimens, and the b* value decreased after repeated firings, which
      resulted in less yellowish specimens. CONCLUSIONS: Imperceptible (DeltaE<1.6) and
      clinically acceptable color changes (DeltaE<3.7) were demonstrated by the alumina
      ceramic system tested.

PMID- 21095401
TI  - Influence of post material and length on endodontically treated incisors: an in
      vitro and finite element study.
AB  - STATEMENT OF PROBLEM: Cast posts require sufficient length for prosthesis
      retention and root strength. For prefabricated metal and fiber posts, the effects
      of different post lengths on the strength and internal stress of the surrounding
      root need evaluation. PURPOSE: The purpose of this study was to examine, using
      both experimental and finite element (FE) approaches, the influence of post
      material and length on the mechanical response of endodontically treated teeth.
      MATERIAL AND METHODS: Sixty extracted incisors were endodontically treated and
      then restored with 1 of 3 prefabricated posts: stainless steel (SS), carbon fiber
      (CF), and glass fiber (GF), with intraradicular lengths of either 5 or 10 mm
      (n=10). After composite resin core and crown restorations, these teeth were
      thermal cycled and then loaded to fracture in an oblique direction. Statistical
      analysis was performed for the effects of post material and length on failure
      loads using 2-way ANOVA (alpha=.05). In addition, corresponding FE models of an
      incisor restored with a post were developed to examine mechanical responses. The
      simulated tooth was loaded with a 100-N oblique force to analyze the stress in
      the root dentin. RESULTS: The SS/5 mm and all fiber post groups presented no
      statistical differences, with mean (SD) fracture loads of 1247 to 1339 (53 to
      121) N. The SS/10 mm group exhibited a lower fracture load, 973 (115) N, and a
      higher incidence of unfavorable root fracture (P<.05). The FE analysis showed
      high stress around the apical end of the long SS post, while stress was
      concentrated around the crown margins in the fiber post groups. CONCLUSIONS: Both
      long and short fiber posts provided root fracture resistance comparable to that
      of SS posts. For metal posts, extending the post length does not effectively
      prevent root fracture in restored teeth.

PMID- 21095402
TI  - Cyclic fatigue properties of cobalt-chromium alloy clasps for partial removable
      dental prostheses.
AB  - STATEMENT OF PROBLEM: Cast cobalt-chromium (Co-Cr) alloy clasps have been widely
      used for prosthodontic treatment, but long-term retentiveness of these clasps is
      not clear. PURPOSE: The purpose of this study was to investigate the residual
      retentive force of 3 types of cast Co-Cr alloy clasps in relation to their
      proportional limits. MATERIAL AND METHODS: Thirty half-round straight clasps and
      30 circumferential clasp assemblies were made from 3 Co-Cr alloys (Hardalloy,
      Regalloy, and Vera PDN) (n=10). All of the straight clasps were subjected to a
      compression-deformation test to obtain data for displacement/load at the
      proportional limit. Two undercut depths (0.25 mm and 0.50 mm, n=5) were included
      in a cyclic fatigue test. Each circumferential clasp assembly was subjected to an
      insertion/removal test on a metal abutment tooth for 7200 cycles to simulate 5
      years of clinical use. The residual retentive force was measured after 360
      cycles; thus, the retentive force of each clasp was recorded 21 times throughout
      the test. The data were subjected to repeated-measures ANOVA (alpha=.05) to
      compare the retentive force of each group of clasps for different periods of
      fatigue testing. The ANOVA. The Student t test (alpha=.05) was used for analysis
      of clasps fabricated with the same alloy but with different undercuts. A linear
      correlation analysis (alpha=.05) was used to test the correlation between
      retentive forces and cycling sequences. RESULTS: The mean values of displacement
      at the proportional limit for the 3 Co-Cr alloys varied from 0.30 mm to 0.36 mm.
      The mean retentive forces of each alloy group decreased dramatically after the
      first cycling phase (P<.05). Thereafter, the decrease was more gradual but was
      still significantly different compared to the original retentive forces (P<.05).
      Compared to clasps in the 0.25-mm undercut group, those in the 0.50-mm undercut
      group exhibited greater mean retentive forces before the cyclic fatigue test
      (P<.05), as well as a greater decrease in the retentive force at the end of the
      test (P<.05). CONCLUSIONS: A negative correlation was found between the retentive
      force of cast Co-Cr alloy clasps and the logarithm of cycling sequences. After a
      test simulating 5 years of service, cast Co-Cr alloy clasps exhibited a residual
      retentive force to satisfy the requirements for clinical use.

PMID- 21095403
TI  - A technique for converting an existing denture into a cast metal-reinforced
      implant-retained overdenture.
AB  - Prosthesis fracture is a common complication associated with implant-retained
      overdentures. A new overdenture can be strengthened by incorporating a cast metal
      reinforcement during processing. The authors describe a technique for converting
      an existing conventional nonreinforced serviceable denture into an overdenture
      that includes a cast metal reinforcement and its attachments.

PMID- 21095404
TI  - Fabrication of a modified repositioning key for relining provisional
      restorations.

PMID- 21095405
TI  - Chemical contamination assessment of the Hudson-Raritan Estuary as a result of
      the attacks on the World Trade Center: analysis of trace elements.
AB  - The attack on the World Trade Center (WTC) resulted in the destruction of
      buildings, and the release of tons of dust and debris into the environment. As
      part of the effort to characterize the environmental impact of the WTC collapse,
      Mussel Watch Program trace element measurements from the Hudson-Raritan Estuary
      (HRE) were assessed for the years before (1986-2001) and after (2001-2005) the
      attack. Trace element measurements in the HRE were significantly higher than
      Mussel Watch measurements taken elsewhere in the Nation. Post-attack trace
      element measurements were not significantly different from pre-attack
      measurements. The impacts of WTC collapse may have been obscured by high ambient
      levels of trace elements in the HRE.

PMID- 21095406
TI  - Preface urologic issues for the internist.

PMID- 21095407
TI  - Pediatric urologic conditions, including urinary infections.
AB  - Genitourinary complaints are common in children, and the busy primary care
      provider must determine initial treatment and assess need for specialty referral.
      Many complaints are self-limited, but some represent disorders that can threaten
      organ function. In this article, an initial approach in the primary care office
      and a guide to specialty referral for pediatric urologic conditions of the
      urinary tract, male genitalia, and female genitalia are suggested.

PMID- 21095408
TI  - Long-term follow-up and late complications following treatment of pediatric
      urologic disorders.
AB  - Many pediatric urologic disorders have sequelae that may affect patients well
      into adulthood. Despite adequate treatment, many patients are at risk for
      progressive urologic deterioration years after surgical reconstruction. While
      many pediatric urologists follow their patients years after surgery, screening
      for late complications is a shared responsibility with primary care providers.
      This article discusses potential late complications and appropriate follow-up for
      patients who have a history of ureteral reimplantation, pyeloplasty, hypospadias
      repair, posterior urethral valve ablation, and intestinal interposition.

PMID- 21095409
TI  - Urinary tract infections in women.
AB  - Urinary tract infection (UTI) is the most common extraintestinal infectious
      disease entity in women worldwide, and perhaps one of the most formidable
      challenges in clinical practice given its high prevalence, frequent recurrence,
      and myriad associated morbidities in the setting of rapidly evolving
      antimicrobial resistance. Achieving timely symptom relief and infection control
      and preventing morbidity, growth of resistant organisms, and recurrent infection
      are often difficult. This article reviews epidemiology and pathogenesis of
      urinary tract infection in women; characterizes common patterns of infection,
      clinical red flags, and appropriate laboratory testing and imaging; explores
      emerging patterns of antimicrobial resistance; and reviews the updated guidelines
      for the treatment of uncomplicated UTI in women.

PMID- 21095410
TI  - Urinary infections in men.
AB  - Urinary tract infections are one of the most common bacterial infections and
      account for significant morbidity and mortality. This review of urinary
      infections in men provides an overview of the general presentation, diagnosis,
      and management of common genitourinary infections in men. The focus of this
      article is on clinical presentation, basic diagnostic evaluation strategies,
      treatment options, and when referral to a specialist is warranted.

PMID- 21095411
TI  - Bladder pain syndrome.
AB  - Bladder pain syndrome is a deceptively intricate symptom complex that is
      diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived
      to be related to the urinary bladder, accompanied by at least one other urinary
      symptom. It is a diagnosis of exclusion in a patient who has experienced the
      symptoms for at least 6 weeks in the absence of any confusable diseases that may
      give rise to the symptoms. Symptoms compatible with the diagnosis are now thought
      to affect up to 3% of the female population in the United States with a 5:1
      female-to-male preponderance. Diagnosis and treatment can be challenging, and
      misdiagnosis as a psychological problem, overactive bladder, or chronic urinary
      infection has plagued patients with the problem.

PMID- 21095412
TI  - Prostatitis and chronic pelvic pain syndrome in men.
AB  - Primary care physicians can and should diagnose, classify, and treat patients
      presenting with acute and chronic prostatitis syndromes. Although the chronic
      syndromes are a challenge to manage, this review article provides the necessary
      background to allow primary care physicians to take on this task. Patients who
      are unfortunate to be diagnosed with a prostatitis syndrome have the best chance
      for successful therapy at initial presentation. Those patients will ultimately
      benefit from an informed and educated physician.

PMID- 21095413
TI  - Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).
AB  - Male lower urinary tract symptoms, benign prostatic hyperplasia, enlargement of
      the prostate, and bladder outlet obstruction are common among aging men and will
      increase in socioeconomic and medical importance at a time of increased life
      expectancy and aging of the baby boomer generation. This article reviews the
      epidemiology, management, and therapeutic options for these conditions. In
      patients bothered by moderate to severe symptoms, providers can make educated and
      differential choices between several classes of drugs, alone or in combination,
      to treat effectively and improve the symptoms in most men. Despite the efficacy
      of medical therapy, there will be patients who require referral to a urologist
      either early, to rule out prostate cancer and other conditions, or later, after
      initial medical therapy and lifestyle management has failed. Perhaps as many as
      30% of patients fail to achieve sufficient symptom improvement with medication,
      lifestyle adjustment, and fluid management, and may require more invasive or
      surgical treatment options.

PMID- 21095414
TI  - Urinary incontinence in women.
AB  - Urinary incontinence is a common and vexing problem that affects millions of
      adults. The main types of incontinence in women are stress, urge, and mixed. It
      is important to delineate the different types to target the treatment options
      better. Treatments include conservative or behavioral modifications,
      pharmacotherapy, and surgical interventions.

PMID- 21095415
TI  - The neurogenic bladder: an update with management strategies for primary care
      physicians.
AB  - Patients with lesions of the central nervous system often have neurogenic bladder
      dysfunction. Lifelong bladder monitoring and management in these patients is
      necessary to prevent severe complications, including renal damage. The urodynamic
      test, performed by neurourologists or other specially trained providers, is the
      definitive test for diagnosis and management of neurogenic bladder dysfunction.
      This article describes the indications and technique of urodynamic testing and
      the interpretation of the results of such testing. The management of patients
      with neurogenic bladder dysfunction is also discussed.

PMID- 21095416
TI  - Assessment and management of irritative voiding symptoms.
AB  - Irritative voiding symptoms are to the urinary tract much as a cough is to the
      pulmonary system, that is, a nonspecific manifestation of multiple potential
      underlying causes. Key to the evaluation and management of patients with these
      symptoms is a clear understanding of the differential diagnosis, the diagnostic
      tests required for evaluation, and the role of specialists in diagnosis and
      treatment. This article outlines a general diagnostic approach for patients with
      irritative voiding symptoms. Treatment approaches for the diseases, as well as
      the initial management that may be performed in the primary care setting, are
      also discussed.

PMID- 21095417
TI  - Urologic aspects of HIV infection.
AB  - Although lifespan has dramatically improved in the human immunodeficiency virus
      positive (HIV+) population, HIV and its treatment continue to be a source of
      substantial morbidity in many organ systems, including the genitourinary tract.
      As the number of long-term survivors increases with advances in antiretroviral
      therapy, age-associated urologic symptoms are also becoming increasingly relevant
      considerations for people living with HIV. Primary care physicians have a major
      role to play in maintaining the genitourinary health of their HIV+ patients. This
      role is of great importance not just for the well-being of the individual patient
      but for the public health, as the genitourinary tract is a common vector for HIV
      transmission. In this article the authors review the management of the
      genitourinary system in patients with HIV infection. Particular consideration is
      given to urinary tract infections, lower urinary tract symptoms, renal
      insufficiency, sexual and fertility problems, and cancers of the genitourinary
      tract. Management algorithms are outlined and indications for referral to a
      urologist are emphasized.

PMID- 21095418
TI  - Assessment of hematuria.
AB  - The most common causes of hematuria in adults include urinary tract infections,
      urolithiasis, benign prostatic enlargement, and urologic malignancy. Once
      hematuria is confirmed, its cause should be investigated through a comprehensive
      history, a focused physical examination, laboratory studies, an image-based
      assessment of the upper urinary tract, and a cystoscopic evaluation of the lower
      urinary system. Prompt evaluation and appropriate referral of patients with
      documented hematuria should be initiated in the primary care setting according to
      the proposed guidelines, and aimed at cost-effective and early detection of
      urologic abnormality.

PMID- 21095419
TI  - Urologic assessment of decreasing renal function.
AB  - The discussion of renal failure as it relates to urology is largely a discussion
      of obstructive uropathy. Obstructive uropathy has been identified in multiple
      series to account for approximately 10% of all cases of renal failure. On a total
      population scale, autopsy series have shown the prevalence of hydronephrosis in
      3% of men and women who are younger than 65 years and 6% of men older than 65
      years. When benign prostatic hypertrophy and renal stone disease are considered,
      obstructive uropathy is also one of the most common indications for surgery. In
      this review, the different causes of obstructive renal insufficiency and
      management options available are discussed.

PMID- 21095420
TI  - Medical and medical/urologic approaches in acute and chronic urologic stone
      disease.
AB  - Urinary stone disease is a condition with far-reaching implications. Patients
      with their initial instance of acute renal colic enter the health care system
      through 2 routes. Severe cases are generally seen in the emergency room, whereas
      more tolerable cases may be seen by primary care physicians. Patients with
      urinary stone disease are then managed in the long-term by a urologist. Timely
      and appropriate treatment of patients with urinary stone disease is essential to
      prevent the development of sepsis and progressive renal insufficiency. This
      article reviews the epidemiology, pathogenesis, presentation, and short- and long
      term management of acute and chronic urinary stone disease.

PMID- 21095421
TI  - Evaluation and management of the renal mass.
AB  - The evaluation and management of renal cell carcinoma (RCC) has evolved in recent
      decades in response to the changing clinical presentation of the disease.
      Traditional teaching suggested that RCC usually presents with signs or symptoms.
      However, RCC discovered this way was usually locally advanced and often
      metastatic, requiring radical nephrectomy in most cases but often having a poor
      prognosis. As contemporary general medical practice began routinely using axial
      body imaging in the evaluation of many nonspecific abdominal complaints, today
      more than 70% of RCC cases identified are "screen-detected" as incidental
      findings having no attributable symptoms. This change has prompted a significant
      RCC stage migration over the past 20 years, with most kidney tumors seen in 2010
      being smaller, organ-confined, and appropriate for nephron-sparing approaches
      with the anticipation of a favorable outcome. The approach to addressing patients
      with these incidentally detected, often localized, small renal masses raises
      different concerns than those for traditional patients presenting with
      symptomatic RCC. This article reviews the modern epidemiology of RCC, outlines
      the components of the evaluation of the incidental renal mass, details the
      current options of management, and discusses the long-term expectations for these
      patients.

PMID- 21095422
TI  - Use and assessment of PSA in prostate cancer.
AB  - Since the introduction of prostate-specific antigen (PSA) screening in the late
      1980s, more prostate cancers have been detected, and at an earlier stage. As a
      consequence, the majority of prostate cancers are now detected years before the
      emergence of clinically evident disease, which usually represents locally
      advanced or metastatic cancer. PSA screening has remained controversial, because
      many of the prostate cancers detected are low grade and slow growing. With this
      long natural history and a median survival without treatment that often
      approaches at least 15 to 20 years, many clinicians and researchers have
      questioned if prostate cancer screening and treatment actually improves survival,
      as many patients will die with prostate cancer rather than of prostate cancer. In
      this review, the authors discuss the rationale for prostate cancer screening and
      present the current guidelines for the use of PSA.

PMID- 21095423
TI  - Evaluation and treatment of erectile dysfunction.
AB  - Erectile dysfunction (ED) is a prevalent and important disease that has been
      associated with various comorbidities. The evaluation of patients with ED should
      include a general health assessment followed by a discussion of reversible
      factors and lifestyle changes that might help preserve erectile capacity.
      Numerous effective treatment options are currently available. A frank discussion
      about use and side effects of these therapies is required to optimize success.
      Although oral pharmacologic treatments can be initiated and monitored by the
      primary care physician, patients who do not experience response to these
      treatments may be best served by referral to a sexual medicine specialist for
      further assessment and consideration of other treatment options. This article
      discusses the physiology and pathophysiology of erectile function in men, how the
      primary care physician may address the clinical problem of ED in practice, and
      when specialty referral is indicated.

PMID- 21095424
TI  - Medical implications of erectile dysfunction.
AB  - Erectile dysfunction (ED) is a common condition in aging men, with a prevalence
      of 52% in men aged 40 to 70 years. It is frequently associated with several
      comorbid conditions, including cardiovascular disease, lower urinary tract
      symptoms, and testosterone deficiency. These conditions often have major
      consequences on the quality of life of patients and require adequate evaluation
      by the primary care practitioner. Complaints of ED, therefore, serve as a marker
      for these conditions and give the practitioner an opportunity to prevent the
      consequences of a delay in treatment. In this article, the evidence behind these
      associations is described.

PMID- 21095425
TI  - Male factor assessment in infertility.
AB  - Male infertility assessment is more than a semen analysis. By interpreting a
      semen analysis, clinicians recognize its uses and limitations. Once understood,
      clinicians can then apply modern techniques of endocrine and radiologic
      evaluation to diagnosis of male reproductive dysfunction. It is important to
      identify patients with infertility not only to allow reproductive potential but
      also to identify a population susceptible to future disease states.

PMID- 21095426
TI  - The diagnosis and management of scrotal masses.
AB  - When evaluating a patient with a scrotal mass, a careful history and
      inguinoscrotal examination are necessary. Malignant scrotal wall, paratesticular,
      or spermatic cord tumors are rare. Scrotal ultrasound can confirm the precise
      location of a mass or rule out the presence of an inguinal hernia. Testicular
      masses deserve a formal workup, with serum tumor markers, a scrotal ultrasound as
      needed, and prompt consultation with a urologist for further staging and
      intervention. Scrotal masses in children are much rarer than in adults and should
      be evaluated by a urologist.

PMID- 21095427
TI  - Assessment and initial management of urologic trauma.
AB  - This article discusses the appropriate assessment, initial management, timely
      referral to a urologist for abdominal, bladder, urogenital, and renal/renal
      collecting system injury. Appropriate laboratory and physical examinations, as
      well as radiologic imaging, are paramount to obtaining accurate diagnosis and to
      providing appropriate treatment.

PMID- 21095428
TI  - Major urologic problems in geriatrics: assessment and management.
AB  - Elderly urologic patients require the same cautions as used in development of
      treatment programs for them in other disciplines. Because of potential
      interference with poor renal function or crossover effects with central or
      peripheral nervous system, however, many urologic drugs must be titrated
      appropriately. In treating cancer, erectile dysfunction, incontinence or urinary
      infection, patient quality of life and life span become dominant factors in
      making therapeutic decisions, by behavioral change, medication, or surgical
      intervention.

PMID- 21095429
TI  - Preface: Obesity in orthopedics.

PMID- 21095430
TI  - Office and hospital needs.
AB  - Obesity is a national phenomenon that affects every facet of the delivery and the
      reception of health care. Orthopedic surgeons are not immune to these influences.
      This article discusses the social and physical environment in which orthopedic
      surgeons evaluate obese patients. Special attention should be paid in both the
      inpatient and outpatient arenas to the different emotional and physical needs
      with which obese patients present in contrast to their lean counterparts.

PMID- 21095431
TI  - Management of upper extremity injuries in obese patients.
AB  - Upper extremity injuries are more prevalent in obese people than in nonobese
      people after low-energy falls. Because splinting and casting are inefficient
      methods of stabilization in the setting of obesity, internal fixation provides
      stability for mobilization and realignment. Morbid obesity adversely affects
      positioning, surgical exposures, and complications associated with operative
      fixation. Avoiding short cuts and complications, morbidly obese patients should
      be able to return to normal functioning.

PMID- 21095432
TI  - Management of femur shaft fractures in obese patients.
AB  - Given the ongoing epidemic of obesity, femoral fracture management in the
      population affected by this condition is likely to become more frequent. Fracture
      treatment in obese patients poses a special challenge given greater difficulty in
      establishing an accurate diagnosis and confirming associated injuries. Adequate
      intraoperative positioning and obtaining accurate reduction and stable fixation
      may require special considerations. Obese patients have a high predisposition for
      complications such as compartment syndrome, nerve injuries, and pressure ulcers,
      and are at increased risk for medical complications given the high prevalence of
      comorbidities. A thorough understanding of the risks associated with obesity and
      the diagnostic and therapeutic challenges involved with femoral shaft fractures
      in this setting is paramount to achieve adequate results.

PMID- 21095433
TI  - Periarticular tibial fracture treatment in the obese population.
AB  - Lambotte's 7 steps of fracture treatment have stood the test of time. Incision,
      preparation of the bone ends, reduction, temporary fixation, permanent fixation,
      closure, and dressing are modified to suit the needs of each fracture and each
      patient. One specific patient characteristic, obesity, has provided complex
      challenges in fracture care. This article reviews the challenges of obesity as
      they relate to the 7 steps of lower extremity periarticular fracture care.
      Specifically, helpful modifications to these 7 steps are provided for the
      treatment of tibial plateau fractures and tibial plafond fractures. As there is
      little published evidence with respect to the treatment of these injuries in the
      obese population, the suggestions that are provided are based on the
      extrapolation from published evidence of fracture care in other areas in patients
      with obesity, logic, and personal experience with fracture care in patients with
      obesity.

PMID- 21095434
TI  - Ankle injuries and fractures in the obese patient.
AB  - Ankle fractures are a common orthopedic injury. Certain ankle injuries have been
      associated with patient demographics such as obesity and smoking. Obese patients
      are more prone to severe ankle injuries. Naturally, these injuries affect the
      lower extremity mobility significantly, which itself is a risk factor for
      obesity. Although obese patients have increased complications across the board,
      there are specific techniques that can be used to assure the best possible
      outcome. The perioperative, surgical, and postoperative considerations as well as
      the outcomes are discussed in this article.

PMID- 21095435
TI  - Percutaneous treatment of pelvic and acetabular fractures in obese patients.
AB  - A body mass index (BMI) greater than 30 is becoming increasingly common in the
      United States. Surgery for pelvic and acetabular fractures in this population is
      particularly problematic because conventional treatment often requires large
      surgical exposures. The surgery for both these fractures is technically difficult
      because of the volume of soft tissue and proneness to complications. Wound
      problems and infections are particularly common after open surgery in obese
      patients, and these increase linearly with the BMI. In this article, we present a
      small consecutive series over 14 months on obese patients who underwent
      percutaneous treatment of their pelvic or acetabular fractures.

PMID- 21095436
TI  - Open treatment of pelvic and acetabular fractures.
AB  - The open operative management of pelvic and acetabular fractures in the obese is
      technically demanding, with a significantly higher rate of complications compared
      with patients who are nonobese. The decision to perform surgery should involve a
      thorough understanding of risks, and patients should be counseled. Careful
      attention should be paid to patient factors; coexisting systemic conditions and
      patient positioning to reduce complications. Wound complications are most
      commonly seen, and techniques to reduce risk should be incorporated. When
      complications occur, aggressive management can result in successful salvage.
      Future areas of study should include methods to reduce risk of surgical site
      infections and improving our understanding of the physiologic alterations that
      occur with obesity. This article summarizes the current literature on open
      treatment of pelvic and acetabular fractures in the obese patient, reviews the
      physiologic adaptations of obesity as they relate to pelvic surgery, highlights
      risk factors for complications, and provides recommendations to reduce the
      incidence of complications.

PMID- 21095437
TI  - Evaluation and treatment of spinal injuries in the obese patient.
AB  - Given the increasing incidence and severity of obesity in the adult population,
      orthopaedic surgeons are evaluating and treating more acutely injured obese
      patients. Management of obese patients is complicated given their body habitus
      and associated medical comorbidities. Although evaluation and treatment are
      almost the same as for nonobese patients, some special considerations are
      necessary to prevent errors in diagnosis and treatment of obese trauma patients.
      This article focuses on spine injuries in obese patients. Predisposition to
      spinal injury, effective evaluation and early management, principles of treatment
      planning, operative technical pearls, and postoperative management are discussed.

PMID- 21095438
TI  - Obesity in pediatric orthopaedics.
AB  - Obesity is a rapidly expanding health problem in children and adolescents and is
      the most prevalent nutritional problem for children in the United States. Some
      believe that obesity has become a major epidemic in American children, with the
      prevalence having more than doubled since 1980. This epidemic has led to a near
      doubling in hospitalizations with a diagnosis of obesity between 1999 and 2005
      and an increase in costs from $125.9 million to $237.6 million between 2001 and
      2005. This article describes some of the orthopaedic conditions commonly
      encountered in overweight/obese children and adolescents, classically infantile
      and adolescent tibia vara and slipped capital femoral epiphysis. Also discussed
      are genu valgum, which has been associated with obesity, and other difficulties
      encountered in providing orthopaedic care to obese children.

PMID- 21095439
TI  - Treatment of knee arthrosis in the morbidly obese patient.
AB  - The purpose of this article is to present the challenges of dealing with the
      morbidly obese patient suffering from degenerative knee arthrosis. Surgery should
      only be undertaken when conservative management has failed and comorbidities
      optimized. Owing to risks related to comorbidities, diligence is necessary before
      proceeding with surgery to lessen the chance of complications-especially
      infection. Evaluation, conservative treatments, preoperative optimization, and
      surgical options are discussed.

PMID- 21095440
TI  - Hip disease and hip arthroplasty.
AB  - There has been a significant increase in the prevalence of obesity in the United
      States over the last 20 years, with the highest percentage in Mississippi. The
      percentage of obese patients undergoing total hip arthroplasty (THA) appears to
      be increasing at an even faster rate. Orthopedic surgeons performing hip
      arthroplasty need to be aware of potential issues to minimize complications
      associated with this population. This article outlines preoperative and
      postoperative care and describes current techniques and tools used by surgeons in
      obese patients to facilitate soft tissue dissection, exposure, implant placement,
      and closure.

PMID- 21095441
TI  - Financial implications of obesity.
AB  - The obesity epidemic continues to grow. As the number of obese people increases,
      it is logical to expect an increasing number of obese patients and increasing
      costs to care for these patients. Orthopedic surgeons will see many of these
      patients who need treatment for injuries and chronic conditions. Care of obese
      patients requires more work and time in providing nonoperative and operative
      care. No system has been proposed to handle reimbursement disparities,
      particularly for providers. The model for health care will change and, along with
      it, should be all parties coming together to address inequalities and inequities
      in care for obese and morbidly obese patients.

PMID- 21095442
TI  - Preface. Renal Transplantation--new insights for a new decade.

PMID- 21095443
TI  - Immunoregulation and tolerance.
AB  - T-regulatory cells (Tregs), a subset of CD4(+)CD25(+) lymphocytes, have the
      functional ability to suppress alloimmune responses in vitro and in vivo.
      Conditions that promote their development and enhance their biological function
      may be attractive for promoting unresponsiveness to organ transplants. Among the
      various mechanistic influences of sirolimus, one of its properties as an in vivo
      agent is to enhance Treg development and function. Therefore, sirolimus is being
      evaluated as a component of strategies to promote tolerance in organ transplant
      recipients. On the other hand, Treg promotion by sirolimus may be offset by other
      properties such as its influence on T-memory cells and B-cell activation. Other
      immunosuppressive agents will likely need to be used in combination with
      sirolimus to control the B-cell response. The development of novel genotypic
      markers of tolerance for liver and kidney transplant recipients should enhance
      our ability to measure the impact of immunosuppressive strategies with respect to
      their ability to promote tolerance in the clinical setting.

PMID- 21095444
TI  - Can the early elimination of calcineurin inhibitors result in clinical benefits?
AB  - Ideally, every kidney should serve its owner for his or her remaining life
      expectancy. Current approaches with immunosuppression have steadily reduced early
      rejection rates. However, we have not seen a comparable improvement in graft
      longevity. Reduction of acute rejection rates should improve survival, unless
      concurrent nephrotoxicity offsets this benefit. An important question is whether
      selective substitution of other drugs/biologicals for calcineurin inhibitors will
      permit adequate immunoprophylaxis, yet improve graft longevity.

PMID- 21095445
TI  - Long-term maintenance therapy with calcineurin inhibitors: an update.
AB  - Combination therapy with mammalian target of rapamycin (mTOR)-inhibitors and
      calcineurin inhibitors (CNIs) provides significant immunosuppressive efficacy. If
      the combination of these agents is not properly optimized, however, important
      risks for synergistic toxicity and long-term complications may result. The
      combination of a CNI and an mTOR-inhibitor is a potent immunosuppressive therapy
      that effectively prevents the incidence of acute rejection, although the
      potential nephrotoxic impact must be considered in the longer term. The trend has
      therefore been to use a low-dose CNI in combination with the mTOR-inhibitor
      sirolimus in order to reduce the risk of nephrotoxicity. Recent studies show that
      an mTOR-inhibitor/low-dose CNI combination is effective in the short term
      following transplantation, and over time, consideration should be given to the
      elimination of the CNI in order to preserve renal function. In the medium to long
      term, it is also possible to consider the elimination of steroids from such a
      protocol. Considering CNI dose minimization or elimination is an essential
      component of this approach, as is the optimal dose and level of both drugs when
      used in combination.

PMID- 21095446
TI  - Can we eliminate both calcineurin inhibitors and steroids?
AB  - Calcineurin inhibitors (CNIs) and steroids, the cornerstone of most
      immunosuppressive regimens in the past 20 years, have undesirable chronic
      effects. This has led to the use of new strategies with sirolimus (SRL) and
      mycophenolate mofetil (MMF). In the SPIESSER study, de novo CNI avoidance and
      early steroid withdrawal were evaluated in 145 renal recipients randomized to
      receive either SRL (n = 71) or cyclosporine (CsA; n = 74). All patients received
      polyclonal antithymocyte globulin for 5 days, MMF, and steroids withdrawn at 6
      months. At 12 months, the incidence of biopsy-proven acute rejection was low
      (14.3% for SRL vs 8.6% for CsA). At 3 years, renal function (Nankivell) was
      better in the SRL group, particularly in patients who remained on treatment
      according to the protocol (71 +/- 22 vs 60 +/- 17 mL/min; P < .01). Steroids were
      withdrawn in 70.5% of SRL-treated patients and in 66.7% of CsA-treated patients.
      In the CONCEPT study, early conversion from CsA to SRL was evaluated in 192 renal
      recipients prospectively randomized at week 12 to switch from CsA to SRL (n = 95)
      or to continue CsA (n = 97). At 12 months, estimated glomerular filtration rate
      (Modification of Diet in Renal Disease) was significantly higher with SRL (61 +/-
      16 vs 54 +/- 15 mL/min; P = .002, intent-to-treat analysis). The significant
      improvement in renal function was maintained at 30 months. In both studies graft
      and patient survival were similar, with better renal function and a tendency for
      fewer cancers observed at follow-up in patients receiving a maintenance regimen
      with SRL and MMF. At 30 months, steroids had been withdrawn in 72% of SRL-treated
      patients and in 70% of CsA-treated patients.

PMID- 21095447
TI  - Rationale for using belatacept in combination with sirolimus.
AB  - Kidney transplantation can be used to replace failing native kidneys; however, it
      requires long-term immunosuppression, and immunological tolerance for this is not
      yet achievable. The cornerstone of immunosuppression is based on calcineurin
      inhibitors, which are nephrotoxic. Therefore, new drugs are being developed that
      provide efficacious immunosuppression and almost no renal toxicity. The first
      family of drugs that have these properties are mammalian target of rapamycin
      inhibitors: these include sirolimus and everolimus. These two drugs, besides
      their immunosuppressive properties, also have beneficial effects regarding
      cytomegalovirus (CMV) infection, which is a very common posttransplantation
      complication. In phase III trials, belatacept, a costimulatory blocker, has also
      been shown to provide a good immunosuppressive effect and also gives a
      significantly better cardiovascular profile than cyclosporine-based
      immunosuppression. However, belatacept can potentially increase infections such
      as CMV. Thus, herein, we describe the rationale for combining belatacept with
      sirolimus for kidney transplant patients.

PMID- 21095448
TI  - Clinical renal transplantation: where are we now, what are our key challenges?
AB  - Today transplant patients have a risk of death a log order higher than someone of
      the same age but without end-stage renal failure and a prognosis akin to the
      normal population with a diagnosis of cancer. Graft losses are mostly from
      chronic allograft nephropathy, and death arises from cardiac disease, malignancy,
      and infection. Most immunosuppression protocols are designed to minimize acute
      allograft rejection, through heavy induction strategies, powerful but toxic
      maintenance therapies, and equally powerful and expensive prophylaxis against
      resultant infections. However, despite all efforts, the 20-year survival of renal
      allografts has not improved much over the past 30 years. New metrics and new
      thinking are needed to change the long-term outcomes. The biological consequences
      of immunosuppression currently require a balance between controlling the
      allograft response and reducing toxicity. To improve, we must both control
      rejection and remove the long-term problems of toxicity and infection. In the
      early period after transplantation, we need maximum immunosuppressive efficacy
      with minimal ischemia-reperfusion injury. Later, we need less immunosuppressive
      efficacy, to avoid risk factors for chronic toxicity, cardiovascular disease, and
      malignancy. One of the key challenges for the next few years will be to learn how
      to individualize therapy using surveillance biopsies and then to validate and use
      noninvasive technologies to guide therapeutic decisions. There is also an urgent
      need to determine the relevant early indicators for measuring long-term success
      to help design better management strategies. The multiplicity of alternatives
      testifies to the absence of a single dominant strategy.

PMID- 21095449
TI  - Can immunosuppressive strategies be used to reduce cancer risk in renal
      transplant patients?
AB  - The risk of renal transplant recipients developing a malignancy is increasingly
      recognized as a major issue impacting long-term overall survival. As
      immunosuppression is thought to contribute to the development of cancer but is
      therapeutically required to protect against kidney rejection, reducing cancer in
      this setting is a challenging objective. An important question is whether there
      is a selective difference between pharmacological immunosuppressants regarding
      effects on malignancy. Both experimental and clinical studies thus far suggest
      that calcineurin inhibitors tend to promote tumor development; mycophenolic acid
      prodrugs such as mycophenolate mofetil have exhibited some capacity to inhibit
      tumors, but the concentrations needed for this effect are well above levels
      sustainable in transplant recipients. In contrast to these immunosuppressive
      substances, despite its potent immunosuppressive effects, rapamycin has
      demonstrated an impressive ability to inhibit de novo tumor development, as well
      as reduce tumor growth once cancer is already established. The antitumor effects
      of rapamycin are being studied extensively and appear to stem from the central
      role that the mammalian target of rapamycin molecule plays in basic cellular
      processes such as cell growth and proliferation, which are also essential for
      neoplasm development. Pilot trials and retrospective analyses of clinical data,
      especially using sirolimus, are highly suggestive that rapamycin can inhibit
      tumors in the clinical transplant setting. Prospective clinical trials are
      currently underway that will bring definitive answers as to whether rapamycin
      treatment can act simultaneously as an immunosuppressive and anticancer agent,
      with the aim of reducing the long-term problem of posttransplant malignancy.

PMID- 21095450
TI  - Clinical insights for cancer outcomes in renal transplant patients.
AB  - The long-term fate of renal transplant recipients has remained relatively
      unchanged over the last 15 years. The cumulative, chronic effects of
      immunosuppression contribute, to a great extent, to the higher, premature
      mortality rates linked to cardiovascular disease and malignancy observed in this
      patient population. Immunosuppression disrupts both antitumor surveillance and
      antiviral activities, and oncogenic viruses predispose to specific malignancies.
      Further, some drugs promote carcinogenesis by mechanisms independent of their
      immunosuppressive effects. In vitro studies have shown that calcineurin
      inhibitors (CNIs) promote tumor progression by a transforming growth factor-beta
      dependent mechanism. In contrast, in vivo mouse models have demonstrated that
      mammalian target of rapamycin (mTOR) inhibitors inhibit metastatic tumor growth
      and angiogenesis. The association between mTOR-inhibitor and reduced malignancy
      has been demonstrated in several studies. United Network for Organ Sharing
      registry data demonstrate that an mTOR-inhibitor either with or without a CNI, is
      associated with a reduced incidence of tumors compared to regimens that do not
      utilize mTOR-inhibitor Five years after renal transplantation, patients in the
      Rapamune Maintenance Regimen study who received sirolimus (SRL)-based CNI-free
      therapy after cyclosporine (CsA) withdrawal at 3 months showed a reduced
      incidence of malignancy compared with those who continued a regimen including
      (CsA) In the CONVERT study, patients who converted to SRL displayed a
      significantly lower malignancy rate (3.8%) at 24 months compared with those who
      continued CNI based therapy (11%; P < .001). A randomized, prospective study to
      evaluate the effect of conversion to SRL from a CNI, compared with continued CNI,
      showed that SRL was associated with a lower rate of nonmelanoma skin cancer
      (NMSC) and a longer time to first biopsy-confirmed new NMSC. An mTOR-inhibitor
      CNI-free regimen should be considered for transplant recipients at high risk for
      cancer development and for those who develop malignancies over the posttransplant
      course.

PMID- 21095451
TI  - Regression of left ventricular hypertrophy in kidney transplant recipients: the
      potential role for inhibition of mammalian target of rapamycin.
AB  - Left ventricular hypertrophy (LVH) contributes to elevated cardiac mortality with
      graft function in renal transplant recipients. Antihypertensive therapy, and
      especially angiotensin-converting enzyme (ACE) inhibitors, proved to be effective
      in regressing the LVH of renal transplant recipients, at least in part by
      interacting with immunosuppressive agents, thus raising the possibility that
      immunosuppressive therapy might affect changes in the left ventricular mass (LVM)
      of recipients. This review mainly focuses on the potential role of mammalian
      target of rapamycin (mTOR) inhibition to regress cardiac hypertrophy in both
      experimental models and in the clinical setting. We comment on the results of
      experimental studies conducted on animal models, which showed regression of
      cardiac hypertrophy by sirolimus (SRL). We also discuss clinical studies that
      show that conversion from calcineurin inhibitors to SRL is effective to achieve
      regression of LVH in both kidney and cardiac transplant recipients, mainly by
      reducing the true left ventricular wall hypertrophy.

PMID- 21095452
TI  - Impact of mammalian target of rapamycin inhibition on autosomal-dominant
      polycystic kidney disease.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the
      progressive development of countless cysts in both kidneys, which compress the
      cyst-free renal parenchyma, leading to a loss of renal function and the need for
      renal replacement therapy and/or kidney transplantation in ~50% of affected
      patients. In animal models of experimental polycystic kidney disease, the
      mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus
      effectively reduce cyst growth and loss of renal function. Furthermore, an
      analysis of renal transplant patients with ADPKD has shown that cystic kidney and
      liver volumes regress more on a sirolimus-based regimen than on a calcineurin
      inhibitor-based immunosuppressive regimen. Several prospective controlled
      clinical trials have been initiated to investigate whether mTOR inhibitors retard
      cyst growth and slow renal functional deterioration in patients with ADPKD. Study
      results are expected in 2010.

PMID- 21095453
TI  - Conclusions from the symposium.
AB  - Despite the progressive improvement in the early outcomes of renal
      transplantation, longer-term outcomes such as graft and patient survival have
      changed little since the introduction of cyclosporine-based immunosuppression.
      The major causes of graft loss after the first year are, first, chronic allograft
      nephropathy (CAN), and, second, death with a functioning graft. Kidney transplant
      recipients are not a homogenous population and so careful consideration is needed
      to individualize care in order to reduce the risk of cardiovascular disease and
      malignancy and improve long-term outcomes. A key component will be the
      consideration of the early and late phases of immunosuppression and the
      modification of immunosuppression in order to address the specific short- and
      long-term risks faced by each of our kidney transplant patients. The insights
      presented and discussed at this symposium will help to inform the design of new
      clinical strategies that may hold potential for improving the quality and
      quantity of life of the wide range of patients that we manage on a daily basis.

PMID- 21095455
TI  - Preface. Up-to-date on COMT enzyme and its inhibitors.

PMID- 21095454
TI  - Contribution of epithelial plasticity to renal transplantation-associated
      fibrosis.
AB  - Every year in the United States, 5000 renal transplant recipients start or
      restart dialysis because of the unusual propensity of these allografts to develop
      interstitial fibrosis and tubular atrophy (IF/TA). Although IF/TA often follows
      one or more identifiable events, our capacity to specifically treat, prevent, or
      even detect IF/TA at an early stage is poor. These limitations are largely
      related to our lack of adequate tools to assess graft failure over time. Data
      accumulated over the past 5 years have demonstrated that tubular epithelial cells
      may react to certain fibrogenic stimuli to engage in the process of epithelial-to
      mesenchymal transition (EMT). In this review, we highlight the current view of
      EMT with a focus on both its role in the context of renal transplantation and the
      potential for utilizing markers of EMT to identify patients undergoing early
      IF/TA.

PMID- 21095456
TI  - Introductory remarks: Catechol-O-methyltransferase inhibition--an innovative
      approach to enhance L-dopa therapy in Parkinson's disease with dual enzyme
      inhibition.
AB  - Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely
      related to the treatment of Parkinson's disease (PD) patients with motor
      fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa
      decarboxylase inhibitor), this indication being so far the only clinical
      application of COMT inhibitors. L-dopa treatment has remained the most effective
      therapy for PD, but its further development has been quite a challenge mainly due
      to the effective metabolism of L-dopa in the human body by multiple pathways,
      decarboxylation and O-methylation being the two most important of them. The
      introduction of clinically effective and safe COMT inhibitors has greatly
      increased the usefulness of L-dopa therapy, but how to utilize the full potential
      of L-dopa is still unsolved leaving a need for more potent COMT inhibitors.

PMID- 21095457
TI  - The catechol-O-methyltransferase gene: its regulation and polymorphisms.
AB  - The catechol-O-methyltransferase (COMT) gene is of significant interest to
      neuroscience, due to its role in modulating dopamine function. COMT is
      dynamically regulated; its expression is altered during normal brain development
      and in response to environmental stimuli. In many cases the underlying molecular
      basis for these effects is unknown; however, in some cases (e.g., estrogenic
      regulation in the case of sex differences) regulatory mechanisms have been
      identified. COMT contains several functional polymorphisms and haplotypes,
      including the well-studied Val158Met polymorphism. Here I review the regulation
      of COMT and the functional polymorphisms within its sequence with respect to
      brain function.

PMID- 21095459
TI  - Catechol-O-methyltransferase enzyme: cofactor S-adenosyl-L-methionine and related
      mechanisms.
AB  - Long-term daily repeated intake of traditional levodopa (L-dopa)/dopa
      decarboxylase inhibitor (DDI) formulations increases the homocysteine synthesis
      in plasma of Parkinson's disease patients with unforeseen consequences, like an
      augmented vulnerability for onset of concomitant non-motor symptoms. Homocysteine
      decrease may therefore be a future therapeutic challenge, which may be achieved
      by supplementation with certain vitamins or by combination of a catechol-O
      methyltransferase (COMT) inhibitor with L-dopa/DDI administration. Monitoring of
      plasma homocysteine concentration may also serve as biomarker for the
      detoxification potential of endogenous, exogenous, and environmental toxins.
      These substrates may also accumulate in the nervous system, since homocysteine
      formation is associated with O-methylation which has a broad detoxification
      potential.

PMID- 21095458
TI  - Distribution and functions of catechol-O-methyltransferase proteins: do recent
      findings change the picture?
AB  - Old and new results show that both catechol-O-methyltransferase (COMT) forms are
      found in all mouse tissues, demonstrating that COMT is a ubiquitous enzyme. Some
      novel findings are obvious when considering differences between old and new
      distribution data. In addition to the brain, membrane-bound form of COMT (MB
      COMT) is found also in most peripheral mouse tissues at about equal amounts as
      soluble form of COMT (S-COMT), suggesting that their functions do not need to be
      very different. There are large differences between the species in the relative
      distribution of S-COMT and MB-COMT. According to the new data, it is evident that
      even in the animal tissues MB-COMT is not associated with the plasma membranes
      but with intracellular membranes, and that S-COMT resides not only in the
      cytoplasm but even in the nucleus.

PMID- 21095460
TI  - Biochemistry and pharmacology of catechol-O-methyltransferase inhibitors.
AB  - Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of
      catechol structured compounds such as catecholamines, catecholestrogens, and L
      dopa. When combined with decarboxylase inhibitor L-dopa is the most efficacious
      treatment for Parkinson's disease. Bioavailability and efficacy of L-dopa
      treatment can be enhanced greatly by the use of COMT inhibitors. This has been
      the driving force for development of new selective and potent COMT inhibitors.
      The success in COMT inhibitor development has generated a tremendous scientific
      interest in the role of COMT in health and disease. COMT inhibitors have also
      helped to clarify the reaction mechanism of COMT, increased interest in its
      structural biology, and physicochemical properties in order to develop even
      better COMT inhibitors. New techniques, especially the transgenic mice, have
      revealed further new aspects about the role of COMT in periphery as well as in
      the brain.

PMID- 21095461
TI  - The chemistry of catechol-O-methyltransferase inhibitors.
AB  - Despite several drawbacks, levodopa (L-dopa) remains the gold standard drug for
      treatment of the symptoms of Parkinson's disease (PD). L-dopa is a pro-drug of
      dopamine and is used to elevate striatal levels of the neurotransmitter. One
      approach to provide a more continuous and sustained delivery of dopamine has
      targeted one of the principal enzymes responsible for metabolic deactivation of L
      dopa, namely catechol-O-methyltransferase (COMT). The chapter will provide a
      perspective of the medicinal chemistry behind the discovery of several COMT
      inhibitors and discuss how certain physicochemical parameters, including aqueous
      solubility and lipophilicity, are thought to influence pharmacokinetic properties
      such as absorption, distribution, and bioavailability.

PMID- 21095462
TI  - Toxicology and safety of COMT inhibitors.
AB  - The development of catechol-O-methyltransferase (COMT) inhibitors for the adjunct
      treatment to levodopa and aromatic L-amino acid decarboxylase (AADC) inhibitors
      in Parkinson's disease started in the late 1950s. The first-generation inhibitors
      were associated with toxic properties: they induced convulsions, or they were
      toxic to the liver. None of them was taken into clinical use. The second
      generation inhibitors entacapone and tolcapone have now been in clinical use for
      over a decade, and some new inhibitors are under development. The main adverse
      events in the use of entacapone and tolcapone are dopaminergic and dependent of
      the concomitant use of levodopa, but the symptoms are generally moderate or mild.
      Among the non-dopaminergic adverse events, diarrhea is the most prominent one
      induced by both entacapone and tolcapone. In clinical use, entacapone has been
      safe, but tolcapone is under strict regulations on liver enzyme monitoring, since
      in the early years, a few hepatotoxicity cases appeared, three of them with fatal
      outcome. The mechanism behind tolcapone-induced liver toxicity has been evaluated
      both in vitro and in vivo, but no clear answer exists at the moment. In the
      regulatory animal studies, both inhibitors have been safe with no reported
      toxicity. Also nebicapone, the latest of the second-generation inhibitors in
      clinical trials has shown some liver enzyme elevations in human subjects. New
      inhibitors with a structure differing from nitrocatechols are under development.
      No safety concerns have been reported connected to COMT inhibiton as such. COMT
      knockout mice are fertile without any pathologies due to the total COMT
      inhibition.

PMID- 21095463
TI  - Catechol-O-methyltransferase inhibitors in preclinical models as adjuncts of L
      dopa treatment.
AB  - Long-term L-dopa treatment is limited by the development of motor complications,
      such as motor fluctuations and dyskinesias. These motor complications are
      postulated to arise from a non-physiological intermittent or pulsatile
      stimulation of striatal dopamine (DA) receptors that normally receive tonic
      stimulation. The concept of continuous dopaminergic stimulation (CDS) proposes
      that therapies providing more continuous stimulation of brain dopaminergic
      receptors are associated with a reduced risk of motor complications. One approach
      to the CDS is to prolong the half-life of L-dopa inhibiting its degradation by
      means of the administration of catechol-O-methyltransferase (COMT) inhibitors, as
      entacapone, a potent, selective, and reversible peripherally acting inhibitor.
      Animal models of L-dopa-induced motor complications can be obtained in monkeys
      and rats with severe damage in the nigrostriatal dopaminergic pathway induced by
      1-methyl-4-phenyl-1-2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6
      OHDA), respectively. The effect of entacapone on L-dopa-induced motor response
      and complications has been widely investigated in preclinical models. The
      administration of entacapone is able to potentiate the long-duration response
      (LDR) to L-dopa and to attenuate L-dopa-induced motor fluctuations and
      dyskinesias in these preclinical models. These effects, however, are not related
      with a normalization of the molecular changes induced by L-dopa in the basal
      ganglia nuclei.

PMID- 21095464
TI  - Problems with the present inhibitors and a relevance of new and improved COMT
      inhibitors in Parkinson's disease.
AB  - Entacapone and tolcapone are reversible COMT inhibitors which have been approved
      for clinical use in patients with Parkinson disease (PD). Nebicapone is a third
      COMT inhibitor which has been studied in humans. COMT inhibitors are used in
      combination with levodopa and a dopa decarboxylase (DDC) inhibitor. Each of them
      has problems either in pharmacokinetics, pharmacodynamics, clinical efficacy, or
      in safety. All three inhibitors have short elimination half-lives, about 2-3h.
      Tolcapone is longer acting and more potent COMT inhibitor than entacapone;
      nebicapone lies in between. However, none of the present inhibitors cause a
      complete peripheral COMT inhibition. Tolcapone and nebicapone have increased more
      levodopa AUC than entacapone which is reflected also in their clinical efficacy.
      The most common adverse event with COMT inhibitors is dyskinesia which is usually
      managed by decreasing levodopa dose. The greatest problem with tolcapone and
      probably also with nebicapone is their liver toxicity which is not seen with
      entacapone. Tolcapone causes severe diarrhea more often than entacapone. Though
      the present COMT inhibitors have improved significantly the treatment of advanced
      PD patients, they still have several problems and weaknesses leaving room for
      developing better COMT inhibitors.

PMID- 21095465
TI  - Catechol-O-methyltransferase and pain.
AB  - In animals, different types of COMT inhibitors, irrespective of their brain
      penetration, are pro-nociceptive in several models of acute and inflammatory
      pain. Similarly, COMT knock-out mice are more sensitive to nociceptive stimuli,
      whereas in mice over-expressing a high activity COMT variant nociceptive
      sensitivity is decreased. COMT knock-out mice also show altered response to
      opioids and stress-induced analgesia. In different rat models of neuropathic
      pain, the action of nitecapone is opposite: it is antinociceptive and
      antiallodynic. Complex actions of low COMT activity may be caused by enhanced
      adrenergic and dopaminergic activities that play different and even contrasting
      roles at different parts of the nociceptive system. Also compensatory changes in
      other neurotransmitters may occur. Pro-nociceptive effects seem to be caused by
      increased activation of peripheral adrenergic beta(2)- and beta(3) -receptors.
      Other properties of COMT inhibitors, like scavenging of oxygen and nitrogen
      radicals, may be important in antiallodynic effects found in neuropathic pain
      models. Increased number of u-opioid receptors in certain brain areas may be
      responsible of enhanced opioid effects associated with a low COMT activity. In
      human pain studies, a low COMT activity is often associated with increased pain
      sensitivity in experimental pain models and with increased pre- and postoperative
      pain in acute clinical situations. As a rule, a simultaneous occurrence of
      several SNPs within the haplotype, causing low COMT activity, is more often
      associated with pain than any single SNP alone. In experimental pain studies, all
      negative findings resulted from concentrating solely on SNP rs4680 (Val158Met).
      Virtually all studies assessing haplotypes were able to confirm an association of
      a low COMT and increased pain. In chronic clinical pain, the effect of COMT
      polymorphisms depends on the pain conditions. Hence, in neuropathic and cancer
      pains, COMT activity is meaningless but in some chronic musculoskeletal pain
      conditions and migraine or headache low COMT activity appears to increase
      incidence and symptoms. A low COMT activity also increases availability of opioid
      receptors and may enhance opioid analgesia and adverse effects at least in cancer
      pains.

PMID- 21095466
TI  - Preface vascular anomalies.

PMID- 21095467
TI  - Vascular anomalies: current overview of the field.
AB  - Vascular anomalies are disorders of the endothelium that can affect each part of
      the vasculature (capillaries, arteries, veins, or lymphatics). Although nearly
      always benign, vascular anomalies can involve any anatomic structure. Significant
      progress in understanding and treating patients with vascular anomalies has been
      made during the past quarter century since the introduction of a biologic
      classification for these lesions.

PMID- 21095469
TI  - Diagnostic imaging of vascular anomalies.
AB  - Medical imaging has become critically important in the diagnosis and treatment
      planning of vascular anomalies. The classification of lesions into fast-flow and
      slow-flow categories, the identification of a soft tissue mass, and the
      determination of the extent of the lesions are all facilitated by the use of
      magnetic resonance imaging, ultrasonography, catheter angiography, and other
      imaging studies. The use of these imaging techniques in the diagnosis and
      assessment of vascular tumors, malformations, and combined malformation syndromes
      is discussed in this article.

PMID- 21095470
TI  - Histopathology of vascular anomalies.
AB  - Over the past decade, many changes and updates have occurred in the world of
      vascular anomalies, including their histopathology. An appreciation has developed
      that a combined team approach is optimal in arriving at a correct diagnosis.
      Technical advances such as immunohistochemical stains for GLUT1, an excellent
      marker for infantile hemangioma, and vascular immunostains such as D2-40, PROX1,
      and vascular endothelial growth factor receptor 3, which distinguish lymphatics
      from arteries and veins, have been of immense help in daily practice.

PMID- 21095468
TI  - Pathogenesis of vascular anomalies.
AB  - Vascular anomalies are localized defects of vascular development. Most of them
      occur sporadically (ie, there is no familial history of lesions, yet in a few
      cases clear inheritance is observed). These inherited forms are often
      characterized by multifocal lesions that are mainly small in size and increase in
      number with patients' age. The authors review the known (genetic) causes of
      vascular anomalies and call attention to the concept of Knudson's double-hit
      mechanism to explain incomplete penetrance and large clinical variation in
      expressivity observed in inherited vascular anomalies. The authors also discuss
      the identified pathophysiological pathways involved in vascular anomalies and how
      it has opened the doors toward a more refined classification of vascular
      anomalies and the development of animal models that can be tested for specific
      molecular therapies.

PMID- 21095471
TI  - Management of hemangiomas and other vascular tumors.
AB  - Vascular tumors of childhood are typically benign. The 4 most common types are
      infantile hemangioma (IH), congenital hemangioma (CH), kaposiform
      hemangioendothelioma (KHE), and pyogenic granuloma (PG). Vascular tumors must be
      differentiated from vascular malformations. Although tumors and malformations may
      appear as raised, blue, red, or purple lesions, their management differs
      significantly.

PMID- 21095472
TI  - Management of capillary malformations.
AB  - Capillary malformations (CMs) are the most common vascular malformations. They
      are comprised of the small vessels of the capillary network in skin and mucous
      membranes. In the vast majority of affected individuals, CMs are isolated and not
      associated with any underlying abnormalities. Depending on size and location,
      however, they may cause significant morbidity due to disfigurement or
      stigmatization and, rarely, herald the presence of an underlying syndrome.

PMID- 21095473
TI  - Management of lymphatic malformations.
AB  - Lymphatic malformation results from an error in the embryonic development of the
      lymphatic system. Clinically, lymphatic malformation is characterized by the size
      of the malformed channels: microcystic, macrocystic, or combined
      (microcystic/macrocystic).This article describes the clinical features,
      diagnosis, and management of lymphatic malformations.

PMID- 21095474
TI  - Management of venous malformations.
AB  - Venous malformation results from an error in vascular morphogenesis. Although
      this condition is present at birth, it may not become evident until childhood or
      adolescence when it has grown large enough to cause a visible deformity or
      symptoms. This article discusses the types, diagnosis, and the nonoperative and
      operative management of venous malformations.

PMID- 21095475
TI  - Management of arteriovenous malformations.
AB  - This article describes the clinical features, diagnosis, and management of
      arteriovenous malformation, capillary malformation-arteriovenous malformation,
      and PTEN-associated vascular anomaly.

PMID- 21095476
TI  - Management of combined vascular malformations.
AB  - Like single-channel-type vascular malformations, combined lesions are categorized
      as slow-flow and fast-flow lesions. Many of the combined vascular malformations
      are associated with soft tissue and skeletal hypertrophy. This article discusses
      the diagnosis, management, and treatment of patients with capillary
      lymphaticovenous malformation, capillary-arteriovenous malformation, and
      capillary-arteriovenous fistulas and congenital lipomatous overgrowth, vascular
      malformations, epidermal nevi, and skeletal anomalies syndrome.

PMID- 21095477
TI  - Special considerations in vascular anomalies: airway management.
AB  - Vascular anomalies are disorders of abnormal vasculogenesis or lymphogenesis. All
      types of vascular anomalies may involve the airway, causing varying degrees of
      upper airway obstruction as well as dysphagia and bleeding. Certain signs and
      symptoms may implicate airway involvement with a hemangioma or vascular
      malformation. It is necessary to distinguish a vascular anomaly from other airway
      lesions such as a congenital cyst. This is accomplished with imaging and
      endoscopy.

PMID- 21095478
TI  - Special considerations in vascular anomalies: operative management of
      craniofacial osseous lesions.
AB  - The treatment of vascular anomalies of the head and neck typically focuses on
      restoration of abnormal structures of the soft tissues. However, vascular
      anomalies can affect the craniofacial skeleton, and osseous reconstruction may be
      indicated. Osseous involvement occurs as either a primary or secondary
      phenomenon. In primary osseous involvement, the vascular anomaly expands the bone
      from within. Secondary osseous involvement occurs when bony hypertrophy develops
      because of increased flow of the surrounding soft tissue. This article focuses on
      the management of the osseous deformities associated with vascular anomalies.

PMID- 21095479
TI  - Special considerations in vascular anomalies: operative management of upper
      extremity lesions.
AB  - The past 3 decades has seen a steady, almost exponential, increase in knowledge
      of vascular anomalies. A useful biologic classification system has evolved. A
      careful physical examination augmented with refined imaging will yield an
      accurate diagnosis and set the stage for treatment. A multidisciplinary team can
      offer treatment options with some degree of predictability. One option is
      surgery, which can be fraught with numerous complications. This article focuses
      on surgical principles and technical pearls in the treatment of these unique
      problems involving the upper limb. If incorporated into routine management, these
      suggestions will improve surgical outcomes.

PMID- 21095480
TI  - Special considerations in vascular anomalies: hematologic management.
AB  - Proper care of the patient with a vascular anomaly requires the expertise of
      multiple specialists. Because of the need for an interdisciplinary approach,
      several vascular anomalies centers have now been developed across the world. A
      hematologist/oncologist provides clinical acumen in establishing a correct
      diagnosis and guiding the medical management of these patients. These patients
      can have complicated coagulopathies and need medical therapy. This article
      emphasizes the hematologic complications and management of these patients.

PMID- 21095481
TI  - Safety profile of abatacept in rheumatoid arthritis: a review.
AB  - BACKGROUND: Abatacept, a soluble human fusion protein that selectively modulates
      the costimulatory signal required for full T-cell activation, is approved for the
      treatment of rheumatoid arthritis (RA) in the United States, Canada, and the
      European Union. Because rare but serious adverse effects have been associated
      with biologic therapies, it is important to assess the safety profiles of these
      agents on an ongoing basis. OBJECTIVE: This article reviews current evidence on
      the safety profile of abatacept in patients with RA. METHODS: PubMed/MEDLINE was
      searched for clinical trials of abatacept using the terms abatacept OR CTLA4Ig,
      rheumatoid arthritis, and safety. Searches of abstracts presented at the 2007
      2009 annual meetings of the American College of Rheumatology, European League
      Against Rheumatism, and Canadian Rheumatology Association were also conducted.
      Reports from clinical trials of at least 6 months' duration that evaluated
      abatacept in adults with RA were included in the review. RESULTS: Seven placebo
      controlled trials and 1 open- label trial were included in the review, as were
      the long-term extensions of 5 of the studies and an integrated safety analysis.
      Abatacept added to methotrexate had an acceptable safety profile in patients with
      RA who had an inadequate response to methotrexate or other traditional disease
      modifying antirheumatic drugs, or who failed to respond to treatment with anti
      tumor necrosis factor agents. In the 5 core trials, discontinuations due to
      adverse events ranged from 1.9% to 8.7% of abatacept recipients and 0.9% to 4.3%
      of placebo recipients. In the integrated safety analysis, serious infections were
      reported in 3.0% of abatacept recipients and 1.9% of placebo recipients; the
      corresponding rates of malignancies were 3.7% and 2.9%. No additional safety
      concerns emerged during up to 7 years of exposure in the long-term extension
      studies. Antibodies to abatacept developed in <=3% of patients, with no
      association found between immunogenicity and adverse events. CONCLUSION: Based on
      the evidence reviewed, abatacept had an acceptable safety profile and was well
      tolerated in patients with RA.

PMID- 21095482
TI  - A meta-analysis of the efficacy and tolerability of interferon-beta in multiple
      sclerosis, overall and by drug and disease type.
AB  - BACKGROUND: Interferon-beta (IFN-beta) is an immunomodulatory agent that has been
      approved in >80 countries worldwide for the treatment of multiple sclerosis (MS)
      with a relapsing course. Several studies have found IFN-beta beneficial in
      reducing rates of relapse, whereas others have reported no benefit in this
      regard. OBJECTIVE: A systematic review and meta-analysis of published placebo
      controlled clinical trials of IFN-beta was conducted to determine the efficacy
      and tolerability of IFN-beta in the maintenance of remission of MS and to examine
      variations in effectiveness according to type of IFN-beta and subtype of MS.
      METHODS: PubMed, Scopus, and the Cochrane Central Register of Controlled Trials
      (1966-May 2010) were searched for English-language reports of placebo- controlled
      trials on the efficacy and/or tolerability of IFN-beta in MS. Three reviewers
      independently examined the abstracts of identified publications for relevance and
      extracted pertinent data from the selected reports. The key efficacy outcomes of
      interest were the number of patients with at least one relapse and the mean
      change in Expanded Disability Status Scale (EDSS) scores. The key tolerability
      outcomes were the number of discontinuations due to adverse events, number of
      deaths, and number of patients with completed suicides or suicide attempts. In
      addition, specific adverse events of interest (flulike symptoms, injection-site
      reactions, injection-site inflammation, myalgia, depression, leukopenia,
      lymphopenia, and increased alanine aminotransferase) were analyzed individually
      and compared between IFN-beta and placebo. RESULTS: Nine randomized, placebo
      controlled clinical trials of IFN-beta met the criteria for inclusion in the meta
      analysis. These studies included a total of 3980 patients with MS (2639 with
      secondary progressive MS, 50 with primary progressive MS, 359 with relapsing MS,
      and 932 with relapsing-remitting MS; 2552 women, 1428 men; mean age, 40.6 years)
      randomized to receive either IFN-beta or placebo. Of those randomized to
      treatment, 1893 received IFN-beta-1a or placebo, 2029 received IFN-beta-1b or
      placebo, and 58 received natural IFN-beta or placebo. The summary relative risks
      (RRs) for at least one relapse compared with placebo were as follows: 0.86 (95%
      CI, 0.76 to 0.97; P = 0.011) for all types of IFN-beta across all subtypes of MS
      (7 trials); 1.11 (95% CI, 0.79 to 1.55) for all types of IFN-beta in secondary
      progressive MS (SPMS) (3 trials); and 0.77 (95% CI, 0.57 to 1.05) for all types
      of IFN-beta in relapsing-remitting MS (2 trials). The summary RR for at least one
      relapse across all types of MS was 0.97 (95% CI, 0.57 to 1.67) for IFN-beta-1a (3
      trials) and 0.92 (95% CI, 0.85 to 1.00; P = 0.042) for IFN-beta-1b (3 trials).
      The summary RR for at least one relapse was 0.93 (95% CI, 0.75 to 1.14) in
      patients with SPMS receiving IFN-beta-1b. The pooled effect sizes for the mean
      change in EDSS score with the IFN-beta doses used in the Prevention of Relapses
      and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis
      Accepted for publication August 19, 2010. study were -1.71 (95% CI, -4.70 to
      1.28) for the 22-MUg dose and -1.71 (95% CI, -4.70 to 1.27) for the 44-MUg dose
      (2 trials). For the tolerability outcomes, the summary RRs were 2.76 (95% CI,
      1.97 to 3.89; P < 0.001) for discontinuation due to adverse events (9 trials),
      1.53 (95% CI, 0.45 to 5.15) for death (3 trials), and 0.86 (95% CI, 0.41 to 1.79)
      for completed suicides and suicide attempts (5 trials). The summary RRs for all
      adverse events of interest (with the exception of depression) were statistically
      significant for all types of IFN-beta compared with placebo across all types of
      MS (P < 0.01). CONCLUSIONS: In this meta-analysis of 9 randomized clinical
      trials, IFN-beta was associated with prevention of relapse compared with placebo
      across all subtypes of MS. However, the effectiveness of IFN-beta appeared to
      vary depending on the type of IFN-beta used and the subtype of MS treated.

PMID- 21095483
TI  - Safety and tolerability of lersivirine, a nonnucleoside reverse transcriptase
      inhibitor, during a 28-day, randomized, placebo-controlled, Phase I clinical
      study in healthy male volunteers.
AB  - BACKGROUND: Lersivirine is a nonnucleoside reverse transcriptase inhibitor
      undergoing clinical development for the treatment of HIV-1. OBJECTIVE: The goal
      of this study was to investigate the safety and tolerability of multiple oral
      doses of lersivirine administered to healthy male subjects to assist in the
      planning of longer term studies. METHODS: This was a randomized, double-blind,
      double-dummy, placebo-controlled, parallel-group, multicenter, Phase I clinical
      study in fasting, healthy male volunteers. Subjects were randomly assigned in a
      ratio of 7:7:4:4 to receive lersivirine 500 mg BID, lersivirine 750 mg once
      daily, efavirenz 600 mg once daily, or placebo once daily for 28 days. Safety and
      tolerability were assessed throughout the study by continuous collection of
      adverse events (AEs), including adverse drug reactions, illnesses with onset
      during the study, exacerbation of previous illnesses, and clinically significant
      changes in physical examination findings. Vital sign measurements and ECGs were
      performed at screening; on day 1 (predose and 2, 3, and 4 hours postdose); on
      days 7, 14, 21, and 28 (predose); at discharge; and at follow-up. Safety
      laboratory tests (including hematology, chemistry, and urinalysis) were performed
      at screening; days 0, 7, 14, 21, and 27; and at follow-up. RESULTS: Of the 66
      healthy male subjects enrolled (age range, 21-51 years; body mass index, 18.1
      29.9 kg/m(2)), 40 were white, 22 were Asian, 3 were black, and 1 was of mixed
      race. There were no clinically significant laboratory abnormalities, including
      changes in lipid profile, liver or renal function test results, or ECG findings.
      Overall, 86% (18/21) of subjects in the lersivirine 500-mg BID group, 81% (17/21)
      in the lersivirine 750-mg once-daily group, 92% (11/12) in the efavirenz 600-mg
      once-daily group, and 92% (11/12) in the placebo group experienced at least one
      treatment-related AE. Eight subjects were permanently discontinued from the
      study; 4 subjects in the efavirenz group (3 of whom participated in the trial at
      the Brussels study center) were permanently discontinued due to AEs considered to
      be treatment related. No subjects receiving lersivirine permanently discontinued
      the study due to treatment-related AEs, although one subject temporarily
      discontinued treatment. In addition, 4 subjects withdrew consent (2 subjects [1
      of whom was at the Brussels study center] receiving lersivirine 750 mg once daily
      and 2 subjects [1 of whom was at the Brussels study center] receiving efavirenz).
      There were no deaths or serious AEs in any of the study groups. CONCLUSION:
      Lersivirine appeared to be well tolerated after 28 days of continuous dosing in
      this small, selected group of young, healthy male volunteers.

PMID- 21095485
TI  - Reversal of refractory sulfasalazine-related renal failure after treatment with
      corticosteroids.
AB  - BACKGROUND: Sulfasalazine is a combination of sulfapyridine and 5-aminosalicylic
      acid and is used as a first-line treatment in inflammatory bowel disease.
      OBJECTIVE: We describe a case of acute interstitial nephritis that presented
      after 7 months of sulfasalazine therapy. Despite the discontinuation of the drug,
      the patient's renal function continued to deteriorate and recovered only when
      systemic corticosteroid treatment was initiated. CASE SUMMARY: A 19-year-old
      white male (weight, 65 kg) presented in November 2006 with upper abdominal pain,
      fever >=38 degrees C, bloody diarrhea, anorexia, and weight loss. Ulcerative
      colitis involving the left colon was diagnosed based on results of a colonoscopy
      and intestinal biopsy, and treatment was initiated with cefprozil 1 g/d,
      mesalamine 3 g/d, methylprednisolone 32 mg/d, and ranitidine 300 mg/d. All drugs
      were administered orally. Cefprozil and ranitidine were discontinued after 10
      days. Mesalamine was discontinued 1 month later because of gastrointestinal
      adverse effects (vomiting and diarrhea), and methylprednisolone was tapered over
      the next 3 months to zero. The patient then had a relapse, and sulfasalazine 2
      g/d orally was administered. Seven months after the initiation of sulfasalazine,
      the patient developed fatigue, nausea, fever more prominent in the afternoon
      (increased from 38 degrees C to 40 degrees C), and nocturia, and he was admitted
      to the hospital. He had no history of renal impairment. Laboratory test results
      showed elevated serum urea and creatinine levels (170 and 7 mg/dL, respectively),
      while kidney ultrasound showed normal kidneys without obstruction. The patient
      had a Naranjo Adverse Drug Reaction Probability scale score of 6, indicating a
      probable adverse drug reaction with sulfasalazine. Based on these findings,
      sulfasalazine-related nephrotoxicity was suspected, and the drug was
      discontinued. During the next 4 days, serum urea and creatinine values increased
      to 212 and 8.3 mg/dL, respectively, and then remained stable for 3 days. A renal
      biopsy was performed, which revealed changes compatible with granulomatous
      interstitial nephritis. The patient received methylprednisolone 500 mg IV for 3
      days, followed by oral administration of methylprednisolone 16 mg/d for 1 month.
      Renal function recovered completely a few days after initiation of
      corticosteroids, and the patient's condition continued to be stable 1 year later
      (eg, serum urea, 34 mg/dL; creatinine level, 0.9 mg/dL). CONCLUSIONS: Although
      this isolated case of sulfasalazine- related interstitial nephritis cannot lead
      to definite conclusions, treatment with corticosteroids was effective in this
      patient and should be considered irrespective of the time of exposure to
      sulfasalazine. However, randomized controlled trials are needed to provide
      evidence regarding the efficacy and tolerability profile of corticosteroids.

PMID- 21095484
TI  - Efficacy and tolerability of a generic and a branded formulation of atorvastatin
      20 mg/d in hypercholesterolemic Korean adults at high risk for cardiovascular
      disease: a multicenter, prospective, randomized, double-blind, double-dummy
      clinical trial.
AB  - BACKGROUND: The reduction in plasma LDL-C concentrations with 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor (statin) therapy has been reported
      to reduce cardiovascular risk and mortality in individuals with or without
      preexisting coronary artery disease and elevated LDL-C concentrations.
      Atorvastatin is a statin used for lowering LDL-C concentrations. A generic
      formulation of atorvastatin is being developed in Korea. This study was
      undertaken for the purposes of marketing the generic formulation. OBJECTIVE: This
      study was designed to compare the efficacy and tolerability of a generic
      formulation of atorvastatin 20 mg/d versus a branded formulation at the same
      dosage in hypercholesterolemic Korean adults at high risk for cardiovascular
      events. METHODS: This 8-week, multicenter, randomized, double-blind, double-dummy
      study was conducted at 10 clinical centers in Korea between September 2008 and
      May 2009. Male and female patients aged 20 to 85 years at high risk for
      cardiovascular events (defined as an elevated LDL-C concentration [>=100 mg/dL])
      were enrolled. Eligible patients were randomly assigned to receive generic or
      branded atorvastatin 20 mg once daily for 8 weeks. The primary end point was the
      percentage change from baseline to 8 weeks in LDL-C concentration. Secondary end
      points were the percentage changes from baseline in total cholesterol (TC),
      triglycerides (TG), HDL-C, apolipoprotein (apo) A1 and B, and high-sensitivity C
      reactive protein concentrations; small, dense LDL (sdLDL) fraction; and
      tolerability. Tolerability was assessed using physical examination, laboratory
      testing, and by recording adverse events (AEs) at each visit. An additional
      secondary end point was the proportion of patients who achieved an LDL-C goal of
      <100 mg/dL. RESULTS: A total of 244 patients were randomized to treatment, and 33
      patients were withdrawn from the study (9 patients did not receive the study
      medication, 11 patients due to AEs, and 13 patients due to withdrawal of
      consent). A total of 211 patients completed the study (50.7% male; 100% Asian;
      mean [SD] age, 61.7 [9.2] years) (106 patients in the group that received
      Accepted for publication October 5, 2010. the generic formulation and 105
      patients in the group that received the branded formulation). LDL-C
      concentrations were reduced from the baseline by 44% and 46% after 8 weeks of
      treatment with the generic and branded formulations, respectively (P = NS). The
      percentage changes from baseline to study end in HDL-C, TC, TG, apo A1, apo B,
      and hsCRP concentrations and sdLDL fraction the proportions of patients who
      achieved the LDL-C goal between the 2 groups did not reach statistical
      significance. The most commonly reported events were hepatobiliary laboratory
      abnormality (1.7%), general somatic discomfort (1.7%), and epigastric pain (0.8%)
      in the group that received the generic formulation, and myalgia (1.7%),
      epigastric pain (0.9%), and elevation of creatinine phosphokinase (0.9%) in the
      group that received the branded formulation. No serious AEs were reported in
      either group. CONCLUSIONS: After 8 weeks of treatment, the differences in the LDL
      C-lowering effects between the generic and branded formulations of atorvastatin
      20 mg/d did not reach statistical significance in these Korean patients at high
      risk for cardiovascular events. Both formulations were generally well tolerated.

PMID- 21095486
TI  - Modulation of CD20 antigen expression after rituximab treatment: a retrospective
      study in patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: CD20 antigen down-modulation by anti-CD20 rituximab treatment is a
      well-recognized phenomenon in patients with non-Hodgkin's lymphoma. However, few
      data are currently available on this topic in other lymphoproliferative
      disorders, in particular in chronic lymphocytic leukemia (CLL). OBJECTIVE: The
      aim of this study was to establish how many patients with CLL show a
      disappearance of CD20 antigen after salvage treatment with rituximab and its
      possible clinical significance. METHODS: We sequentially analyzed CD20 expression
      by flow cytometry in patients treated with rituximab in combination with other
      agents for relapsed/resistant disease. RESULTS: Eleven white patients with CLL (6
      females, 5 males; median age, 71.6 years [range, 60-84 years]) were included in
      the study. Three of the 11 patients were not positive for CD20 due to complete
      response at baseline. Four of the remaining 8 patients (50%) lacked CD20 antigen
      on neoplastic cells after monoclonal antibody treatment. Two of them developed
      Richter's syndrome and died within 4 months. The phenomenon was transient in the
      other 2 patients, who were alive after a follow-up of 25 and 26 months,
      respectively, with CD20-positive recurrent disease. CONCLUSIONS: In this study,
      CD20 antigen disappearance in patients with CLL treated with rituximab-containing
      salvage regimens occurred in 4 of 8 (50%) tested patients, half of whom developed
      Richter's syndrome. [Note: Since the initial writing and submission, a third
      patient developed Richter's syndrome.] In 2 patients (50%), CD20 returned at
      progression.

PMID- 21095487
TI  - Intuitiveness, ease of use, and preference of a prefilled growth hormone
      injection pen: a noninterventional, randomized, open-label, crossover,
      comparative usability study of three delivery devices in growth hormone-treated
      pediatric patients.
AB  - BACKGROUND: Growth hormone (GH) is used to treat pediatric and adult GH
      deficiency (GHD) and growth failure in, among others, patients with Turner
      syndrome or children born small for gestational age. To improve treatment
      adherence, self-injection devices should be easy to learn, easy to use, and well
      accepted, especially in pediatric patients. Several GH pen devices are available,
      each with distinct features designed for specific patient needs. OBJECTIVES: This
      study compared injection time and intuitiveness of a prefilled test injection
      device (Norditropin FlexPro, Novo Nordisk A/S, Bagsvaerd, Denmark) with those of
      2 commercially available durable injection devices (easypod, Merck Serono SA,
      Geneva, Switzerland; and Genotropin, Pfizer Inc, New York, New York) in GH
      treated pediatric patients. Dose accuracy, application errors, intuitiveness,
      usability, device features, ease of learning, ease of use, and overall preference
      were also assessed. METHODS: This noninterventional, randomized, open-label,
      crossover study enrolled patients aged >=10 to <18 years who were diagnosed with
      GHD or Turner syndrome or were born small for gestational age. Patients were
      allocated to an intuitiveness group (without instruction) or an instruction group
      and assigned to 1 of 3 sequences of device testing. For each device, time taken
      to deliver a mock injection of test medium (FlexPro) or GH (easypod and
      Genotropin) into an Eppendorf tube and the delivered dose were measured. Dose
      accuracy and application errors were assessed by a health care professional.
      Patients assessed the intuitiveness (intuitiveness group only), device features,
      ease of learning, ease of use, and overall preference of the devices using
      questionnaires. RESULTS: Included in the study were 56 patients (mean [SD] age,
      13.6 [2.1] years; 63% male; GHD, 44 patients; Turner syndrome, 3; born small for
      gestational age, 9): 30 in the intuitiveness group and 26 in the instruction
      group. In the intuitiveness group, the mean (SD) mock injection time was
      significantly shorter with FlexPro (47.0 [49.0] seconds) than with the easypod
      (219.2 [72.6] seconds; P < 0.001) or the Genotropin pen (95.1 [78.4] seconds; P <
      0.01). In the instruction group, injection time was also shortest with FlexPro
      (30.7 [10.8] seconds vs 59.6 [13.1] with easypod and 40.7 [18.6] with the
      Genotropin pen; both, P < 0.001). Most patients (70%) ranked FlexPro as the most
      intuitive device (easypod, 0%; Genotropin, 30%). In both the intuitiveness and
      instruction groups, a significantly greater proportion of patients considered
      FlexPro easiest to learn compared with the easypod and Genotropin devices (both,
      P < 0.001), although more patients preferred the easypod or Genotropin devices
      than FlexPro with regard to appearance (intuitiveness group: FlexPro, 8 patients;
      easypod, 9; and Genotropin, 13; instruction group: FlexPro, 4; easypod, 10; and
      Genotropin, 12) and quality (intuitiveness group: FlexPro, 6 patients; easypod,
      10; and Genotropin, 14; instruction group: FlexPro, 8; easypod, 12; and
      Genotropin, 6), and easy- pod's delivery feedback feature was preferred by more
      patients (intuitiveness group: FlexPro, 8 patients; easypod, 14; Genotropin, 8;
      instruction group: FlexPro, 8; easypod, 14; and Genotropin, 4). Dose accuracies
      (as assessed by weighing the delivered dose and calculating variation in the
      delivered dose by device) were 4.6% with FlexPro, 14.6% with easypod, and 20.6%
      with the Genotropin pen in the intuitiveness group, and 2.7% with FlexPro, 5.8%
      with easypod, and 24.4% with the Genotropin pen in the instruction group.
      CONCLUSION: In this study, Norditropin FlexPro was associated with shorter
      injection times, higher dose accuracy, and greater intuitiveness, and was rated
      as easier to learn compared with the easypod and Genotropin devices.

PMID- 21095488
TI  - Adjunctive levetiracetam in patients aged 1 month to <4 years with partial-onset
      seizures: subpopulation analysis of a prospective, open-label extension study of
      up to 48 weeks.
AB  - BACKGROUND: In a recent double-blind, placebo-controlled study, adjunctive
      levetiracetam (LEV) was reported to be effective and well tolerated during 5-day
      treatment in patients aged 1 month to <4 years with partial-onset seizures. A
      study was planned to fulfill the regulatory requirement to evaluate the long-term
      safety of LEV as adjunctive therapy for partial-onset seizures in pediatric
      patients. OBJECTIVE: This study evaluated the long-term effectiveness and
      tolerability of adjunctive LEV in infants and young children with partial-onset
      seizures. METHODS: This was a prospective, open-label, outpatient, multicenter
      study (N01148; ClinicalTrials.gov identifier NCT00152516) conducted as an
      extension of a previously published study (N01009; NCT00175890). Patients were
      enrolled from 3 sources, as follows: (1) patients who had completed study N01009;
      (2) patients who had failed screening for entry into study N01009 but fulfilled
      the eligibility criteria for entry into this study; and (3) patients who were
      directly enrolled. The study consisted of a 2- to 4-week retrospective baseline
      period (and a 3- to 10-day prospective baseline period for directly enrolled
      patients), a 2- to 8-week uptitration/conversion period, and a maintenance
      period. Eligible patients were required to have epilepsy with partial-onset
      seizures, treated with a stable regimen of 1 or 2 antiepileptic drugs. Patients
      received adjunctive LEV, 20 to 80 mg/kg/d, for up to 48 weeks (total study
      duration). The primary variable for effectiveness was the percentage reduction
      from baseline in the weekly frequency of partial-onset seizures, as recorded in
      patients' diaries. Data for effectiveness were also analyzed by age strata (1
      month to <1 year, 1 to <2 years, and 2 to <4 years). Neuropsychological
      assessment was conducted with the Bayley Scales of Infant Development, Second
      Edition (BSID-II). All analyses were performed on observed data, and the last
      observation-carried-forward approach was not used. The intent-to-treat (ITT)
      population was defined as all patients who took at least one dose of LEV during
      the study. Treatment-emergent adverse events (TEAEs) were assessed by
      observation, spontaneous reporting, standard questions, review of diary cards,
      and neuropsychologists' clinical reports. Additional measures included physical
      and neurologic examinations, vital signs, ECGs, routine blood chemistry, and
      routine hematology assessments. RESULTS: The study included 152 patients in the
      ITT population. In total, 51.3% (78/152) of the patients were male, and mean (SD)
      age was 23.5 (12.4) months. The mean LEV maintenance dose was 56.1 (16.2)
      mg/kg/d, and the median (Q1-Q3) treatment duration was 287.8 (209.0-295.5) days.
      Ninety-seven patients (63.8%) completed the study. The BSID-II subpopulation
      included 51 patients. During maintenance, the overall median (Q1-Q3) percentage
      reduction from baseline in the weekly frequency of partial-onset seizures was
      56.0% (-10.9% to 92.8%), which was sustained over time and appeared comparable
      across the age strata (1 month to <1 year, n = 25, 50.9%; 1 to <2 years, n = 48,
      58.0%; and 2 to <4 years, n = 59, 55.0%). The overall responder rate (ie, >=50%
      reduction from baseline in weekly partial-onset seizures) was 53.8% (71/132), was
      maintained over time, and was consistent across the age strata (1 month to <1
      year, 52.0%; 1 to <2 years, 56.3%; and 2 to <4 years, 52.5%). Mean BSID-II raw
      scores for psychomotor development and behavioral functioning remained static,
      whereas mental development appeared to improve over time, although this was not
      tested statistically. At least one TEAE was reported in 143 patients (94.1%). The
      most frequently reported TEAEs were pyrexia (60/152; 39.5%), upper respiratory
      tract infection (42/152; 27.6%), and vomiting (28/152; 18.4%). The most common
      TEAEs affecting the central nervous system were convulsion (25/152; 16.4%),
      irritability (19/152; 12.5%), and somnolence (16/152; 10.5%). Most TEAEs (77.0%)
      were mild or moderate in intensity. CONCLUSION: Adjunctive LEV treatment for up
      to 48 weeks was associated with effective and sustained seizure control and had
      an acceptable tolerability profile in this small, selected population of infants
      and young children aged 1 month to <4 years with partial-onset seizures.

PMID- 21095489
TI  - Assessing treatment effects in the "real world".

PMID- 21095490
TI  - Does type of bolus insulin matter in the hospital? Retrospective cohort analysis
      of outcomes between patients receiving analogue versus human insulin.
AB  - BACKGROUND: Poor glycemic control in hospitalized patients has been associated
      with increased morbidity and mortality. Research suggests that analogue bolus
      insulin may be more effective in achieving blood glucose (BG) control compared
      with human bolus insulin. OBJECTIVE: This study compares mortality, length of
      stay (LOS), costs, and BG control in hospitalized patients receiving either
      analogue or human bolus insulin. METHODS: This retrospective cohort analysis used
      data from January 1, 2004, to December 31, 2007, within the Health Facts database
      (Cerner Corporation, Kansas City, Missouri). Nonsurgical adult patients who
      received exclusively analogue or human bolus insulin during hospitalization were
      included in the study. Propensity score matching and multivariate regression
      analyses were used to compare patients treated with analogue versus human bolus
      insulin. The study outcomes were in-hospital mortality, hospital LOS among
      survivors (to avoid potentially short hospitalizations among nonsurvivors
      distorting results), and hospitalized BG control (present vs absent), defined as
      having a mean BG of 70 to <200 mg/dL during hospitalization. RESULTS: In total,
      35,049 participants met the inclusion criteria and 5568 of 7754 patients in the
      analogue group were matched by their propensity scores to patients in the human
      bolus group (mean age, 67.1 years; 53% women; 77% white). On propensity score
      analysis, analogue bolus insulin was associated with lower mortality (relative
      risk [RR] = 0.52; 95% CI, 0.45-0.61) and shorter LOS (0.668-day reduction; 95%
      CI, 0.44-0.89) compared with human bolus insulin. However, analogue insulin was
      associated with only a modest benefit for BG control (RR = 0.88; 95% CI, 0.81
      0.95). The multivariate regression analysis produced similar findings.
      CONCLUSIONS: In this cohort of hospitalized patients, analogue bolus insulin was
      associated with lower mortality, shorter LOS, and modestly better BG control
      compared with patients treated with human bolus insulin. These results highlight
      the need for a randomized controlled clinical trial comparing outcomes by bolus
      insulin type in the hospital setting to determine a true mortality benefit.

PMID- 21095491
TI  - Pharmacokinetic and pharmacodynamic comparison of two recombinant human
      erythropoietin formulations after single subcutaneous administration: an open
      label, sequence-randomized, two-treatment crossover study in healthy Korean male
      volunteers.
AB  - BACKGROUND: Recombinant human erythropoietin is indicated for the treatment of
      anemia resulting from chronic renal failure or chemotherapy. It is also used for
      patients at high risk for transfusions because of significant blood loss during
      surgery. A new recombinant human erythropoietin (epoetin alfa) that excludes
      fetal bovine serum and human serum albumin from among its ingredients was
      developed in Korea. This study was planned as part of a product development
      project at the request of the Korean regulatory agency. OBJECTIVE: The aim of
      this study was to compare the pharmacokinetic and pharmacodynamic characteristics
      of a new recombinant human erythropoietin (test) formulation with an existing
      branded (reference) formulation after a single subcutaneous administration.
      METHODS: An open-label, sequence-randomized, 2-period, 2-sequence, 2-treatment
      crossover study was conducted. Healthy male subjects were randomly assigned with
      a random number table into 1 of 2 sequence groups, and each subject was given
      recombinant human erythropoietin 4000 IU SC in the upper arm as the test
      formulation in one period and the reference formulation in the other period,
      according to the sequence group. Each period was separated by a 4-week washout
      period. Serial blood samples were taken up to 120 hours after drug administration
      for the pharmacokinetic assessments and up to 240 hours for reticulocyte counts
      as the pharmacodynamic end point. Pharmacokinetic analysis was performed without
      baseline correction. Adverse events (AEs) were collected by spontaneous reporting
      of the subjects or solicited by asking general health-related questions. RESULTS:
      Twenty healthy men (mean [range] age, 25.6 [21-36] years; height, 175 [167-187]
      cm; weight, 70 [57.6-85.5] kg) were enrolled in and completed the study. The mean
      (SD) baseline erythropoietin plasma concentrations were 10.4 (2.4) mIU/mL for the
      test formulation and 10.8 (3.5) mIU/mL for the reference formulation. After the
      injection of 4000 IU SC per subject, the erythropoietin plasma concentrations
      reached a maximum at a median T(max) of 10 hours for both formulations (range:
      test formulation, 7.00-95.95 hours; reference formulation, 6.98-24.13 hours). The
      mean (SD) C(max) values for the test and reference formulations were 74.34
      (30.63) and 80.46 (30.56) mIU/mL, respectively; the mean AUC(0-last) values were
      3664 (731.5) and 3553 (723.2) mIU.h/mL. The ratios of the geometric mean
      (test/reference) for C(max) and AUC(0-last) were 0.92 (90% CI, 0.81-1.05) and
      1.03 (90% CI, 0.98-1.09). The mean baseline hemoglobin, hematocrit, and
      reticulocyte counts were 15.4 g/dL, 45.5%, and 49.6 . 10(3)/MUL, respectively,
      for the test formulation and 15.5 g/dL, 45.3%, and 47.5 . 10(3)/MUL for the
      reference formulation. The mean reticulocyte counts slowly reached T(max) for
      both formulations at a median of 120 hours after administration (test
      formulation, 120.0 hours [range, 95.5-240.8 hours]; reference formulation, 120.1
      hours [range, 72.0-240.5 hours]). The mean (SD) maximum reticulocyte counts for
      the test and reference formulations were 77.7 (12.2) . 10(3)/MUL and 80.7 (15.2)
      . 10(3)/MUL, respectively; values for area under the effect curve to the last
      observation (AUEC(0-last)) were 14,781.5 (2439.2) . 10(3)/MUL . h and 14,783.8
      (2415.4) . 10(3)/MUL . h. The 2 agents did not exhibit any significant
      differences in maximum reticulocyte counts or AUEC(0-last). During the study, a
      total of 6 AEs were reported, which were mild in severity. After the
      administration of test formulation, 1 case each of rhinorrhea, epigastric
      discomfort, and joint sprain (left ankle) were reported. After the administration
      of reference formulation, 2 cases of rhinorrhea and 1 case of cough were
      reported. CONCLUSION: In this small, selected group of healthy male volunteers,
      there were no significant differences in pharmacokinetic parameters or effects on
      reticulocytes between a test formulation and a reference formulation of
      recombinant human erythropoietin.

PMID- 21095492
TI  - Comparative bioavailability and tolerability of a single 20-mg dose of two
      fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy
      Chinese male volunteers: an open-label, randomized-sequence, two-period crossover
      study.
AB  - BACKGROUND: The proprietary formulation of fluoxetine hydrochloride is an
      antidepressant of the selective serotonin reuptake inhibitor class.
      Pharmacokinetic studies investigating the bioequivalence of generic and branded
      formulations are needed to market generic fluoxetine in China. OBJECTIVE: The aim
      of this study was to compare the bioavailability and tolerability of the proposed
      generic formulation with the established reference formulation of fluoxetine
      hydrochloride 20 mg in a fasting, healthy Chinese male population. METHODS: This
      10-week, open-label, randomized-sequence, single-dose, 2-period crossover study
      was conducted in healthy native Han Chinese male volunteers. Eligible subjects
      were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test
      or reference formulation, followed by a 35-day washout period and administration
      of the alternate formulation. Doses were administered after a 12-hour overnight
      fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0
      t), AUC(0-infinity), and t(1/2)), blood samples were obtained over a 672-hour
      period after dosing. Plasma concentrations of fluoxetine and its active
      metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The
      formulations were to be considered bioequivalent if the ln-transformed ratios
      (test/ reference) of C(max) and AUC were within the predetermined bioequivalence
      range of 80% to 125%, as established by the US Food and Drug Administration, and
      if the P values were <0.05 for the 90% CIs. Signs and symptoms of adverse effects
      of fluoxetine hydrochloride such as nausea, vomiting, insomnia, somnolence,
      anxiety, and nervousness, as well as any untoward effects, were collected using a
      daily written questionnaire and recorded by the study physicians. Tolerability
      was assessed using monitoring of vital signs, physical ex- amination, ECG, and
      routine blood and urine tests, along with blood biochemical tests, at the start
      as well as at the end of the study. RESULTS: Twenty-four subjects were enrolled
      and completed the study (mean [SD] age, 24.4 [2.3] years [range, 20-30 years];
      weight, 63.6 [8.5] kg [range, 51.2-86.8 kg]; height, 1.72 [0.07] m [range, 1.57
      1.91 m]). The AUC values for fluoxetine were not consistent with a normal
      distribution, reflecting the existence of 2 different populations (poor and
      extensive metabolizers). Data from the one poor metabolizer were excluded from
      the pharmacokinetics data summarized. In extensive metabolizers, the mean (SD)
      C(max) for fluoxetine with the test formulation was 11.786 (3.459) ng/mL and
      T(max) was 5.48 (2.06) hours. With the reference formulation, the corresponding
      values were 11.754 (3.292) ng/mL and 6.26 (5.77) hours, respectively. The t(1/2)
      values with the test and reference formulations were 30.86 (7.61) and 30.96
      (6.91) hours, respectively. For norfluoxetine, mean C(max) with the test
      formulation was 14.177 (4.957) ng/mL and T(max) was 58.48 (31.67) hours; the
      corresponding values for the reference formulation were 13.828 (4.838) ng/mL and
      57.91 (25.75) hours. The t(1/2) values with the test and reference formulations
      were 130.91 (42.04) and 128.79 (52.72) hours, respectively. For fluoxetine, the
      90% CIs (in extensive metabolizers only) for the In-transformed C(max), AUC(0
      168), and AUC(0-infinity) were 92.0% to 108.4%, 95.7% to 110.3%, and 97.4% to
      111.3%, respectively (all, P < 0.001). For norfluoxetine, the 90% CIs for the ln
      transformed C(max), AUC(0-672), and AUC(0-infinity) were 93.7% to 110.7%, 98.9%
      to 111.4%, and 98.8% to 110.9% (all, P < 0.001). No period or sequence effects
      were observed for any pharmacokinetic variable in the extensive metabolizers. No
      adverse events were reported by the volunteers or found with results of clinical
      laboratory testing. CONCLUSIONS: This single-dose study found that the test and
      reference formulations of fluoxetine hydro- chloride met the regulatory criteria
      for bioequivalence in these fasting, healthy Chinese male volunteers. Both
      formulations appeared to be well tolerated.

PMID- 21095493
TI  - [Acne moves again and again].

PMID- 21095494
TI  - [Recent data on epidemiology of acne].
AB  - The prevalence of acne is about 80% in the majority of the countries worldwide.
      Moderate and severe acne account for 20% of all cases. Prognostic factors of acne
      severity were identified: hyper seborrhea, an age of beginning of acne after 17
      years or pre pubertray, extension of acne lesions to the trunk, stress for the
      two sexes, and notion of family acne (hereditary). The role of cigarette and food
      remains discussed. Acne of the adult (man and woman) is in increase and is
      estimated at 40% of the adults. In addition, recent epidemiologic data reveal
      that the acneic subject consults little the doctor (on average, one out of two)
      and, in the same way, only one young person out of two teenagers declaring a
      severe acne is treated. Actually, acne is regarded today as a chronic disease
      requiring treatment of induction and maintenance.

PMID- 21095495
TI  - [Pathophysiological advances in acne].
AB  - Acne is a chronic disorder caused by multiple factors. Recent advances suggest
      that inflammation plays an initial role and Propionibacterium acnes plays a major
      role by initiating, maintaining and extending acne.

PMID- 21095496
TI  - [Adult acne in women].
AB  - Acne, a disease of adolescence, is actually quite frequent in the adult and may
      be on the rise. It is particularly observed in women, but this may result from
      consultation bias. Stress and hormone disorders are blamed with no tangible
      evidence. The clinical aspect in females is quite specific: inflammatory acne in
      the lower facial region. This acne is highly chronic and recurrent, requiring
      adaptation of contraception and often isotretinoin.

PMID- 21095497
TI  - [Acne and diet].
AB  - The classical opinion of dermatologists on the absence of a dietary effect on
      acne is challenged by the discovery of so-called primary populations with no acne
      and by the demonstration of a possible role played by dairy products in the diet
      of adolescents. The role played by IGF1 as the effector of these dietary effects
      has a number of elements of proof. From a practical point of view, however, it is
      too early to provide particular advice to patients other than eating a balanced
      diet.

PMID- 21095498
TI  - [Psychological impact of acne vulgaris].
AB  - Through its visible clinical aspect, acne induces a significantly impaired body
      image which is not correlated to clinical severity. This diminished body image
      and the resulting psychosocial behaviour must be considered to optimize the
      treatment. In addition, depressive disorders related to bodily concern are
      frequently observed during adolescence period and faced with these bodily
      transformations, acne can be a source of anxiety. It is therefore important to
      spot the symptoms of depression and indeed treat them if they are persistent,
      because they impair "self-image" and have an influence on the wish to "take care
      of oneself".

PMID- 21095499
TI  - [A therapeutic algorithm in acne: why?].
AB  - The acne is one of the cutaneous affections the most frequently seen by the
      dermatologist in his or her office. But it is also one of the affections, for
      which the therapeutic decisions vary more for patients of identical severity.
      This justifies firstly to be able to have a scale of severity of acne easily
      usable in an office, in order to homogenize our evaluation of severity of acne,
      and thus to be able to propose a prescription adapted to the severity of acne
      patient taking of course account of the recent recommendations of the AFSSAPS.

PMID- 21095500
TI  - [Isotretinoin, depression and medias].
AB  - Acne is a frequent disease with a strong impact upon quality of life. The most
      effective treatment of severe acne is isotretinoin. Cases of suicid have been
      reported during isotretinoin treatments in adolescents and were mediatised. Now a
      day, the link between isotretinoin intake and psychiatric troubles is not
      established at populational level. The pressure of public and medias led the
      French Drug Agency to send a letter to health professionals to summarize the
      scientific question. An explanative video is on line on the website of the French
      Society of Dermatology www.dermato-info.fr. This video summarizes the state of
      the art concerning the context of isotretinoin for public, dermatologists and
      other physicians To summarize isotretinoin is the drug for severe acne in case of
      failure of first line classical treatment. Dermatologists must stay the first
      line prescribers reminding that adolescence is a fragile period.

PMID- 21095501
TI  - [Current role of light-based treatments and procedures in acne].
AB  - A range of light-based treatments in acne have been used including visible light,
      specific narrowband light, intense pulsed light, pulsed dye laser with or without
      photosensitizing agents. The clinical studies in this topic have often lacked
      controls and included only small numbers of patients The purpose of this
      presentation was to assess the level of evidence in the literature on this
      subject, remember the scientific rational and targets of light-based therapy and
      remember procedures for approving the devices in the US.

PMID- 21095502
TI  - [Dermo-cosmetic approach to acne by the dermatologist].
AB  - Cosmetics contribute to the success of anti-acne treatments, by providing optimal
      hygiene, compensating the irritation and dryness induced by medications, and
      allowing use of adapted cosmetics and sun protection. The most contemporary
      products can contribute directly to obtaining a therapeutic benefit, either alone
      or with medications. The dermatologist's advice is essential. The choices are
      guided by information from laboratories and the efficacy and tolerance tested by
      use. Overall, cosmetology is considered by the dermatologist as part of the
      management of acne devoid of notable side effects. In day-to-day medical
      practice, the dermatologist prescribes medications and dermo-cosmetics together,
      an approach that is also found in managing other disorders such as atopic
      dermatitis. This mode of operation is part of a true healthcare protocol in which
      each part has its importance, from daily hygiene to isotretinoin, to ensure
      complete and individualized management.

PMID- 21095504
TI  - Maxillofacial Oncologic and Reconstructive Surgery Group (MORS): at harvest time.

PMID- 21095503
TI  - [What's new in acne? New therapeutic approaches].
AB  - Well-known topical and systemic treatments for acne have advanced little over the
      last 10 years. However, many therapeutic approaches are being evaluated both in
      terms of topical and systemic treatments. The purpose of this paper is to show
      the progress of innovative drug projects in treating acne. The topical use of new
      formulations using lipid nanoparticles and microspheres could help for new
      products based on anti-androgens or retinoids more concentrated and better
      tolerated. New active agents such as topical antimicrobial peptides, inhibitors
      of ectopeptidase, omiganan pentahydrochloride, antisense oligonucleotides, lauric
      acid are many original ways to explore for the treatment of acne. New treatment
      regimens for doxycycline and isotretinoin would increase tolerance. Dapsone has
      been evaluated for isotretinoin-resistant forms. Phototherapy narrowband light
      (blue or red) can find its place in the strategy for the management of acne.
      Finally, acne vaccines could be developed too.

PMID- 21095505
TI  - Most patients with asymptomatic, disease-free third molars elect extraction over
      retention as their preferred treatment.
AB  - PURPOSE: To answer the clinical question, "Among patients presenting for
      evaluation of their third molars (M3s), do those who choose M3 extraction,
      compared with those who choose M3 retention, differ in important demographic,
      clinical, anatomic, or radiographic ways?" MATERIALS AND METHODS: The
      investigators implemented a retrospective cohort study and enrolled a sample
      composed of patients presenting for M3 evaluation. The primary predictor variable
      was the clinician's assessment of M3 status categorized as asymptomatic, disease
      free (Sx-/D-); asymptomatic, disease present (Sx-/D+); symptomatic, disease free
      (Sx+/D-); and symptomatic, disease present (Sx+/D+). The secondary predictor
      variable was treatment recommendation grouped as extraction, retention, or
      patient choice. The primary outcome variable was the subject's treatment
      decision: extract or retain M3s. Data analyses were performed using bivariate and
      multiple regression methods. RESULTS: The study sample comprised 249 subjects
      (855 M3s) with a mean age of 27.3 +/- 10.4 (median = 25.0) years. Of the 855 M3s
      evaluated, 37.3% were Sx-/D-, 0.6% were Sx+/D-, 51.1% were Sx-/D+, and 11.0% were
      Sx+/D+. The treatment recommendations were retention (6.5%), extraction (55.7%),
      or patient choice (37.8%). Subjects chose M3 extraction 82.1% of the time. In the
      adjusted multiple logistic regression model, increasing age, presence of Sx-/D-
      M3s, and a treatment recommendation of M3 retention were factors statistically (P
      < .05) associated with subject treatment choice of M3 retention. CONCLUSION: When
      offered the choice of retention or extraction, most patients (60%) with
      asymptomatic, disease-free M3s elected for extraction. When M3 symptoms or
      disease were present, more than 95% of patients chose extraction as the preferred
      treatment.

PMID- 21095506
TI  - Are personality patterns and clinical syndromes associated with patients' motives
      and perceived outcome of orthognathic surgery?
AB  - PURPOSE: A study of surgical-orthodontic patients was performed to assess whether
      signs of personality patterns and psychologically defined clinical syndromes
      influenced patients' motives for treatment, perceived oral function, self
      concept, social interaction, and overall satisfaction with treatment. PATIENTS
      AND METHODS: The sample consisted of 92 adult surgical-orthodontic patients. They
      filled out 3 questionnaires from Kiyak et al: one on motives for treatment;
      another on perceived oral function, self-concept, and social interaction; and a
      third on satisfaction with treatment outcome. The Millon Clinical Multiaxial
      Inventory III was used for classification of personality patterns and clinical
      syndromes. RESULTS: Patients with signs of a schizoid personality pattern
      expressed stronger presurgical motives than other patients. Concerning self
      concept and social interaction, the patients showing signs of personality
      patterns and clinical syndromes, in general, perceived themselves as worse than
      the other patients. However, differences were only evident before treatment.
      Overall satisfaction was independent of the psychological profile. Histrionic and
      narcissistic personality patterns seemed to be overrepresented among surgical
      orthodontic patients compared with the general population. CONCLUSION: Patients
      who showed signs of certain personality patterns and clinical syndromes improved
      most from treatment in terms of self-concept and social interaction, and such
      traits did not influence their degree of satisfaction.

PMID- 21095507
TI  - Lymphoepithelial cyst of mouth floor.

PMID- 21095508
TI  - Bovine papillomavirus DNA can be detected in keratinocytes of equine sarcoid
      tumors.
AB  - Bovine papillomavirus (BPV)-1 and -2 is linked to equine sarcoids, a commonly
      observed skin tumor in horses that is of considerable veterinary importance.
      Previous studies using in situ hybridization have detected BPV DNA only in
      fibroblasts and not in keratinocytes of sarcoids. In contrast, normal equine skin
      latently infected with BPV shows a dysplastic epithelium without dermal changes,
      similar to lesions induced by other papillomavirus types infecting the
      epithelium. The first goal of our study was to describe the epidermal and dermal
      characteristics of several stages in sarcoid development. Next, we explored
      whether BPV can infect epidermal cells in the horse using real-time PCR on laser
      micro-dissected keratinocytes and fibroblasts. We found that latently infected
      normal skin samples and a subset of early stage sarcoids show dysplastic,
      koilocyte-like epithelial changes. BPV DNA was detected in keratinocytes in 40%
      of the samples with these particular epithelial properties, whereas advanced
      sarcoids only had BPV DNA in the fibroblasts. These data may indicate a novel and
      intriguing pathway of BPV infection in the horse composed of a first step of
      keratinocyte infection, followed by migration of viral material towards the
      dermis resulting in infection of sub-epidermal fibroblasts and their fully
      transformed phenotype. Additionally, an example of co-existence of a dermal BPV-1
      and an epidermal BPV-2 infection in the same lesion is shown, indicating that
      horses can harbor infection with more than one BPV type at the same time.

PMID- 21095509
TI  - Development and application of a real-time TaqMan((r)) qPCR assay for detection
      and quantification of 'Candidatus Mycoplasma haemolamae' in South American
      camelids.
AB  - Two alpacas from a herd in southwest Switzerland died for unknown reasons.
      Necropsy revealed chronic weight loss and pale mucous membranes. Infection with
      hemotropic mycoplasmas was suspected and subsequently confirmed by molecular
      methods. In order to investigate the epidemiological situation in this herd, a
      real-time TaqMan((r)) qPCR assay for the specific detection and quantification of
      hemoplasma infection in South American camelids was developed. This assay was
      based on the 16S rRNA gene and amplified 'Candidatus Mycoplasma haemolamae' DNA,
      but not DNA from other hemoplasmas or non-hemotropic mycoplasma species. The
      lower detection limit was one copy/PCR, and the amplification efficiency was
      97.4%. In 11 out of 24 clinically healthy herd mates of the two infected alpacas,
      'Candidatus M. haemolamae' infection was confirmed. No correlation was found
      between bacterial load and clinical signs or anemia. The assay described herein
      enables to detect and quantify 'Candidatus M. haemolamae' and may be used in
      future studies to investigate the prevalence, pathogenesis and treatment follow
      up of hemoplasma infections in South American camelids.

PMID- 21095510
TI  - Using CF0218-ELISA to distinguish Chlamydophila felis-infected cats from
      vaccinated and uninfected domestic cats.
AB  - Chlamydophila felis is a causative agent of acute and chronic conjunctivitis and
      pneumonia in cats. Cats can be vaccinated with killed or attenuated C. felis.
      However, current serodiagnostics cannot distinguish these cats from naturally
      infected cats. This causes difficulty of early diagnosis and seroepidemiological
      survey for C. felis. We previously reported that C. felis CF0218 can be used as a
      C. felis-infection-specific diagnostic antigen in experimentally infected and/or
      vaccinated cats. In this study, we evaluated an enzyme-linked immunosorbent assay
      using recombinant CF0218 as antigen (CF0218-ELISA) to detect anti-C. felis
      antibody in 714 sera of domestic cats whose histories of vaccination against C.
      felis are known. The 44 vaccinated cats were 93% negative using CF0218-ELISA;
      half of these scored positive by immunofluorescence assay (IFA) using C. felis
      infected cells as antigen. The 670 non-vaccinated cats had CF0218-ELISA
      positivity rates that were statistically in agreement with IFA (18% vs. 21%).
      These results show that CF0218, which was identified as a C. felis-infection
      specific antigen, is a useful serodiagnostic antigen to distinguish naturally C.
      felis-infected cats from vaccinated and non-infected cats.

PMID- 21095511
TI  - Pharmacogenetics in medico-legal context.
AB  - Medico-legal autopsy is the primary method in determining the cause and manner of
      death when the death is suspected to be unnatural. In some of these autopsies,
      the death remains ambiguous, even after a complete autopsy including histological
      investigation and toxicological screenings. In cases where there are no
      morphological abnormalities, medico-legal genetics may offer additional means to
      provide knowledge of possible genetic mutations, which may have initiated the
      process or predisposed the individual to stress risk conditions leading to death.
      One class of ambiguous deaths consists of drug-related deaths where the
      interpretation of the toxicological results are not clear. In such situations
      post mortem genotyping and the analysis of metabolite rations may provide an
      insight to the findings. A few cases demonstrating the potential strength of
      pharmacogenetics in medico-legal context has been published. However, there is a
      paramount need for serious scientific studies before the field of post mortem
      pharmacogenetics can be utilized in routine medico-legal analyses casework and
      brought routinely into courtroom.

PMID- 21095512
TI  - [Liver fibrosis in hepatitis B: a dynamic process].
AB  - Liver fibrosis is a common complication of chronic hepatitis B leading to the
      progressive destruction of normal tissue architecture or the replacement of
      hepatocytic tissue with fibrous tissue. The final outcome of this process is
      liver cirrhosis, which is the major cause of morbidity and mortality in chronic
      viral hepatitis. Fibrogenesis is closely related to activation of the main type
      of fibrocompetent cells in the liver: hepatic stellate cells. Experimental models
      have allowed a better understanding of the dynamics of fibrosis, the biological
      processes related to its progression and regression and the development of new
      anti-fibrotic drugs. Nevertheless, it is universally accepted that such an anti
      fibrotic treatment will be efficient only after hepatitis B virus eradication.
      Furthermore, early fibrosis is more amenable to regression than more advanced and
      highly organized liver cirrhosis.

PMID- 21095513
TI  - [Influence of treatment on long-term evolution of chronic hepatitis B].
AB  - The treatment of chronic hepatitis B is essentially based on the use of
      nucleoside or nucleotide analogues, which lead to viral suppression in the
      majority of cases. Viral suppression is associated with normal ALT values and
      progressive histological improvement of not only necroinflammatory lesions but
      also fibrosis. Regression of cirrhosis can be observed in severe cases. With the
      use of second-generation nucleoside or nucleotide analogues, the risk of mutation
      resistance is rare or inexistent. Finally, negativation and seroconversion of the
      HBs antigen can be observed in the medium-term. This seroconversion is usually
      associated with a decreased risk of complications and morbidity-mortality
      improvement.

PMID- 21095514
TI  - [HBsAg quantification: virological significance].
AB  - HBsAg is a classic marker of hepatitis B virus infection. Since the levels of
      serum HBsAg are correlated to those of intrahepatic cccDNA, HBsAg quantification
      indirectly reflects the number of infected hepatocytes. The kinetics of serum
      HBsAg decline seems to be a predictive marker for sustained virological response,
      and clearance of HBsAg. This new tool may be clinically relevant for the
      monitoring and optimization of hepatitis B treatments. To fulfill this objective,
      prospective studies are still warranted for the the spread of sensitive and
      standardized techniques standardization of the quantification assays and to
      define cut off values with clinical predictive values.

PMID- 21095515
TI  - [HBsAg seroclearance: prognostic value for the response to treatment and the long
      term outcome].
AB  - Chronic hepatitis B is a major cause of liver disease worldwide, ranking as the
      first cause of cirrhosis and hepatocellular carcinoma. Hepatitis B surface
      antigen (HBsAg) is usually used as a qualitative marker for the diagnosis of
      hepatitis B virus (HBV) infection. HBsAg clearance is the closest to cure outcome
      as one can expect to achieve in hepatitis B. Support for this comes from natural
      history studies demonstrating increased length of survival, lower rates of
      hepatic decompensation, reduction in the frequency of hepatocellular carcinoma,
      and regression of liver fibrosis in patients who clear HBsAg. HBsAg seroclearance
      may occur spontaneously at a yearly incidence of 1-2%, preceded usually by a long
      period of inactive disease. Interferon treatment enhanced HBsAg seroclearance by
      approximately three-fold in western studies and sixfold in Asian studies compared
      with non-treated patients. Pegylated interferon induced a 10-15% yearly rate of
      HBsAg seroclearance in patients who developed sustained virological response in
      clinical trials. By contrast, treatment with nucleos (t) ides analogues did not
      significantly affect the rate of HBsAg seroclearance, especially in patients with
      hepatitis B e antigen (HBeAg) - negative disease. Recently, serum HBsAg has been
      shown to be a surrogate marker of covalently closed circular DNA (cccDNA)
      concentration in the liver. Quantification of serum HBsAg has also been recently
      shown to be a promising tool for monitoring virologic response in HBeAg-negative
      patients treated with pegylated interferon.

PMID- 21095516
TI  - [Analogs combination therapy in chronic hepatitis B: when and how?].
AB  - Hepatitis B virus (HBV) genomic variability is responsible for the complexity of
      the viral quasi-species and its evolution during the course of infection. The
      persistence of infected cells promotes the selection of drug-resistant strains.
      The development of nucleoside analogs without cross-resistance has provided a
      rationale for combination therapy. De novo combination, with low genetic barrier
      drugs, prevents the emergence of resistance in the short-term for drugs with a
      low genetic barrier and improves the control of infection. Long-term studies are
      needed to determine whether de novo combination is beneficial for analogs with a
      high genetic barrier as well. The add-on strategy is a standard in case of
      emergence of resistant mutants. This strategy needs to be implemented as early as
      possible before the virological breakthrough, especially if the viral suppression
      is sub-optimal. Clinical trials are mandatory in order to assess whether a) de
      novo combination is better than an early add-on strategy; and b) whether in case
      of sub-optimal viral suppression, an early add-on strategy is better in the long
      term than a switch to a more potent drug with a high genetic barrier.

PMID- 21095517
TI  - [Long-term therapy for chronic hepatitis B in HIV co-infected patients].
AB  - As human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are acquired
      through the same routes of contamination, the prevalence of HBV serological
      markers found in the HIV-infected population is approximately 7%. Liver-related
      mortality and morbidity is higher in HIV/HBV co-infected patients than in HBV
      mono-infected patients. Both viruses must be considered before a treatment
      decision is made. According to the European consensus conference on the treatment
      of chronic hepatitis B and C in HIV coinfected patients, treatment is based on
      whether there is an existing indication of anti- HIV therapy or not. In patients
      with no indication of anti-HIV therapy, drugs with dual anti-viral activity
      (lamivudine, entecavir, tenofovir disoproxil fumarate) should not be used due to
      the risk of developing HIV-resistance. Interferon or adefovir in combination with
      telbivudine are recommended. In patients with an indication of anti-HIV therapy,
      a backbone of highly active anti-retroviral therapy should include tenofovir in
      combination with lamivudine or emtricitabine. The same regimen is recommended in
      patients who develop lamivudine resistance.

PMID- 21095518
TI  - [Treatment of chronic hepatitis B: adherence and safety].
AB  - Second generation nucleos (t) idic analogues result in a complete viral
      suppression after 48 to 96 weeks of therapy in most patients, regardless of the
      virus (HBV genotype, wild type or pre-C mutant), the underlying liver disease
      (cirrhosis or not) or the immune status (mono- or HIV/HBV co-infection). This
      antiviral efficacy may result in HBe or HBs seroconversion. Its clinical impact
      is important since inactivation of necroinflammation allows, in the absence of
      liver comorbidities, a stabilisation then a reversal of fibrosis and cirrhosis,
      and consequently a decrease in the occurrence of carcinomatous or non
      carcinomatous complications. The future issues for long-term anti-HBV therapy
      will be adherence on the one hand and safety on the other hand. Therapeutic
      failures are mainly related to poor adherence more than to viral resistance.
      Adherence of patients has to be optimized by therapeutic education and education
      of physicians. Long-term safety has to be systematically evaluated. More than the
      neuromuscular or metabolic side effects (lactic acidosis), the renal and bone
      related adverse events have to be monitored, followed-up and anticipated by good
      clinical practices.

PMID- 21095519
TI  - [Treatment has a positive impact on the long-term evolution of chronic hepatitis
      B].

PMID- 21095520
TI  - Preface special topics in tropical dermatology.

PMID- 21095521
TI  - Buruli ulcer: Advances in understanding Mycobacterium ulcerans infection.
AB  - Buruli ulcer (BU), caused by the environmental organism Mycobacterium ulcerans
      and characterized by necrotizing skin and bone lesions, poses important public
      health issues as the third most common mycobacterial infection in humans.
      Pathogenesis of M ulcerans is mediated by mycolactone, a necrotizing
      immunosuppressive toxin. First-line therapy for BU is rifampin plus streptomycin,
      sometimes with surgery. New insights into the pathogenesis of BU should improve
      control strategies.

PMID- 21095522
TI  - Outbreak of nontuberculous mycobacterial disease in the central Pacific.
AB  - Approximately 10% of the island population of Satowan (population, 650 persons),
      a small, remote coral island in the central Pacific, suffers from an acquired,
      chronic, disfiguring skin condition known locally as "spam." This skin disease
      has affected the island population since shortly after World War II. An
      investigation in 2007 revealed that this skin disease is caused by a
      nontuberculous mycobacterial infection closely related to Mycobacterium marinum.
      This article reviews the fascinating history of this skin disease on Satowan, its
      distinctive clinical presentation, and recommendations for diagnosis and
      treatment of clinically similar skin lesions in Pacific Islanders.

PMID- 21095523
TI  - Dermatology aboard the USNS COMFORT: Disaster relief operations in Haiti after
      the 2010 earthquake.
AB  - On the 12th of January 2010, Haiti was struck by a 7.0 Richter magnitude
      earthquake that devastated its already fragile capital region. Approximately
      230,000 people died immediately or during ensuing weeks, mostly due to acute
      trauma. Countless others suffered significant life- or limb-threatening injuries.
      As a part of the United States' response to this tragedy, eventually named
      Operation Unified Response, the United States Navy deployed hundreds of
      physicians and other medical response individuals on a hospital ship. Operation
      Unified Response was a military joint task force operation augmented by
      governmental and nongovernmental organizations. Its mission was to bring medical
      and logistical support to the region.

PMID- 21095524
TI  - Community-associated methicillin-resistant Staphylococcus aureus skin infections
      in the tropics.
AB  - Skin and soft tissue infections (SSTI) caused by Staphylococcus aureus are very
      common, particularly in children, in tropical regions. The proportion of S aureus
      SSTI caused by community-associated methicillin-resistant S aureus (CA-MRSA)
      varies according to region, but is up to 25% in some areas. There are diverse CA
      MRSA clones, including several that harbor Panton-Valentine leukocidin. Key
      predisposing factors for staphylococcal infections are scabies infestation,
      overcrowding, poor hygiene, and inadequate water supplies. In the setting of a
      community outbreak of staphylococcal SSTI, interventions intended to improve
      personal and community hygiene are likely to be the most practical, effective,
      and achievable. Options for oral treatment of clinical infections caused by CA
      MRSA include clindamycin and trimethoprim-sulfamethoxazole. Although rapid
      diagnostics are now available, and 2 vaccines have reached clinical trials,
      neither of these is likely to be of use in tropical, developing regions in the
      near future.

PMID- 21095525
TI  - Mosquito-borne hemorrhagic fevers.
AB  - Arboviruses continue to be a significant source of disease, especially in regions
      where their insect hosts are endemic. This article highlights these diseases,
      with particular focus on dengue, yellow fever, and viral hemorrhagic fever. A
      general background is provided, as well information concerning diagnosis and
      treatment.

PMID- 21095526
TI  - Immune reconstitution inflammatory syndrome and tropical dermatoses.
AB  - The human immunodeficiency virus (HIV) pandemic has disproportionately affected
      tropical regions of the world, where dermatoses, such as leprosy and
      leishmaniasis, rarely encountered in temperate climates, are endemic. Although
      the introduction of highly active antiretroviral therapy (HAART) has been
      lifesaving, a few patients undergoing HAART experience clinical deterioration
      caused by immune reconstitution inflammatory syndrome (IRIS). This article
      explores the range of tropical dermatoses that are reported to date with
      associated IRIS events.

PMID- 21095527
TI  - Arsenical keratoses in Bangladesh--update and prevention strategies.
AB  - Arsenic is considered a Class I human carcinogen by the International Agency for
      Research on Cancer because of its increased risk for skin cancer, as well as
      internal cancers, such as lung and bladder cancer. Arsenic contamination of
      drinking water in Bangladesh has been called the "largest mass poisoning of a
      population in history." This inorganic arsenic contamination is of natural
      origin, with arsenic thought to be released to the groundwater from the
      surrounding sediment. Arsenicosis and its risk factors and prevention and
      management are discussed in this article.

PMID- 21095528
TI  - Chagas disease: coming to a place near you.
AB  - Chagas disease, or American trypanosomiasis, is a parasitic infection caused by
      the flagellate protozoan Trypanosoma cruzi, an organism that is endemic to Latin
      America. While Chagas disease is primarily a vector-borne illness, new cases are
      emerging in non-endemic areas due to globalization of immigration and non
      vectorial transmission routes. This article discusses the mode of transmission,
      evolving epidemiology, pathogenesis, diagnosis, treatment and prevention and
      control of the disease.

PMID- 21095529
TI  - Dermatology in Botswana: The American Academy of Dermatology's Resident
      International Grant.
AB  - In 2008, the American Academy of Dermatology began sponsoring North American
      dermatology residents to travel to Botswana in sub-Saharan Africa and spend 4 to
      6 weeks working with the Botswana-UPenn Partnership, the Baylor International
      Pediatrics AIDS Initiative, Princess Marina Hospital, and surrounding smaller
      district hospitals. During their time in Botswana, the residents staff the busy
      outpatient dermatology clinic and see adult and pediatric inpatients at Princess
      Marina Hospital in Gaborone, the capital city. The residents also travel to 4
      rural hospitals to provide clinical services to patient and education to local
      health care providers. The program goals include providing direct care to the
      people of Botswana, capacity-building through dermatologic education for local
      clinicians, and educating the residents about delivering dermatologic care in
      resource-limited and culturally diverse settings and using teledermatology
      consulting services. Since the start of the program, more than 1500 patients have
      been seen, and 35 residents would have completed the program by the end of 2010.

PMID- 21095530
TI  - Effectiveness of gentian violet and similar products commonly used to treat
      pyodermas.
AB  - The term pyoderma encompasses a variety of distinct entities including impetigo
      (bullous and nonbullous), erysipelas, cellulitis, folliculitis, and
      staphylococcal scalded skin syndrome. Treatment of pyodermas centers around wound
      care and appropriate antibiotic selection. Triphenylmethane dyes, such as gentian
      violet, represent a unique group of compounds that act as antiseptics and have
      shown clinical efficacy as antibiotics in a variety of pyodermas, including those
      secondary to methicillin-resistant Staphylococcus aureus. Given their low cost,
      ease of application, and favorable side effect profile, triphenylmethanes must be
      considered legitimate treatment options for pyodermas, particularly in the face
      of continued and emerging bacterial resistance.

PMID- 21095531
TI  - Cutaneous leishmaniasis in Mali.
AB  - While not as common as in other parts of the world, cutaneous leishmaniasis is
      endemic to countries in Africa, particularly in the north, central, east, and
      south. Sporadic case reports of cutaneous leishmaniasis in countries spanning
      West Africa have allowed scientists to propose an endemic belt in sub-Saharan
      Africa ranging from Senegal to Cameroon. While the presence of cutaneous
      leishmaniasis in West Africa is well established, there is a paucity of data
      regarding the parasite species, vector, and reservoir responsible for the disease
      in this part of the continent. This article focuses on cutaneous leishmaniasis in
      Mali, West Africa.

PMID- 21095532
TI  - Albinism in Africa: stigma, slaughter and awareness campaigns.
AB  - Oculocutaneous albinism is an autosomal recessive disorder characterized by a
      lack of pigment in the hair, skin, and eyes. Albinism is caused by defective or
      absent tyrosinase, an enzyme necessary for melanogenesis. Although rare in the
      western world, albinism is quite common in sub-Saharan Africa, likely as a result
      of consanguinity. Albinism has long been associated with stigma and
      superstitions, such as the belief that a white man impregnated the mother or that
      the child is the ghost of a European colonist. Recently, a notion has emerged
      that albino body parts are good-luck charms or possess magical powers. These body
      parts may be sold for as much as $75,000 on the black market. As a result there
      have been over 100 albino murders in Tanzania, Burundi, and other parts of Africa
      in the past decade, which is now beginning to garner international attention and
      thus prompting novel legislation. To ameliorate the plight of individuals with
      albinism in Africa, a coordinated effort must be organized, involving medical
      professionals (dermatologists, ophthalmologists, oncologists), public health
      advocates and educators, social workers, human rights and antidiscrimination
      activists, law-enforcement agencies, and governmental support groups. The main
      issues that should be addressed include skin cancer prevention education, stigma
      and discrimination denouncement, and swift prosecution of albino hunters and
      their sponsors.

PMID- 21095533
TI  - Innate immunity and Leishmania vaccination strategies.
AB  - Despite the ubiquity and severity of parasitic diseases and our desire to prevent
      them, there are no effective antiparasitic vaccines in widespread clinical use.
      This review focuses on strategies for development of a vaccine against cutaneous
      leishmaniasis as a representative parasitic disease of paramount interest to
      dermatologists and all who care for patients who live in or travel to the
      developing world. Any effective strategy will require attention to the central
      role that host innate immunity plays during induction of durable resistance to
      these virulent protozoa. The cell types, receptors, and molecules of the innate
      immune system that will likely play a role in any effective vaccine against
      cutaneous leishmaniasis are reviewed.

PMID- 21095534
TI  - Female genital mutilation: what every American dermatologist needs to know.
AB  - Female genital mutilation (FGM) has become more common in the United States with
      increased immigration to the United States of individuals from areas where the
      practice is endemic. Although the root causes of FGM may be multiple, the
      practice is banned in the United States on all women under age 18 and is
      increasingly being outlawed by individual state legislatures. American
      dermatologists should expect to see a growing number of patients having undergone
      FGM who may present with complications ranging from keloids and epidermal cysts
      to clitoral neuromas and abscess formation. While treatment of such complications
      is often elusive and unsuccessful, recognition of the practice may prevent future
      patient abuse and death. The eradication of FGM will require the concerted
      efforts of many individuals, both within and outside of the health care field,
      with dermatologists poised to play a crucial role in diagnosis and management in
      the near future.

PMID- 21095535
TI  - Widespread use of toxic skin lightening compounds: medical and psychosocial
      aspects.
AB  - Hyperpigmentation disorders and skin lightening treatments have a significant
      impact on the dermatologic, physiologic, psychologic, economic, social, and
      cultural aspects of life. Skin lightening compounds, such as hydroquinone and
      topical corticosteroids, are often used to treat hyperpigmentation disorders,
      such as melasma, or lighten skin for cosmetic purposes. Despite their established
      effectiveness, a multitude of dermatologic and systemic complications have been
      associated with these agents. Regulatory agencies have also recognized the
      adverse effects of skin lighteners and many countries around the world now forbid
      the production and sale of these compounds, although this prohibition has not
      significantly curtailed distribution. Dermatologists and users of cosmetic
      products should be aware of the various components in bleaching compounds, their
      potential adverse effects, and alternative options for skin lightening.

PMID- 21095536
TI  - Human immunodeficiency virus and leprosy: an update.
AB  - Coinfection with human immunodeficiency virus (HIV) has a major effect on the
      natural history of many infectious diseases, particularly mycobacterial diseases.
      Early in the HIV epidemic, it was predicted that HIV infection would worsen
      leprosy outcomes, with more patients developing lepromatous disease, an impaired
      response to multidrug therapy and fewer reactions. However, studies on the
      epidemiologic and clinical aspects of leprosy suggest that the course of leprosy
      in coinfected patients has not been greatly altered by HIV. In contrast,
      initiation of antiretroviral treatment has been reported to be associated with
      activation of subclinical Mycobacterium leprae infection and exacerbation of
      existing leprosy lesions. With regular new discoveries about the interaction of
      leprosy and HIV, the need to maintain research in this field is of considerable
      importance.

PMID- 21095537
TI  - Foreword: Gastroenteropancreatic system and its tumors: Part 1.

PMID- 21095538
TI  - Preface: Gastroenteropancreatic system and its tumors: Part 1.

PMID- 21095539
TI  - The history and development of the gastroenteropancreatic endocrine axis.
AB  - Fundamental medical principles, such as hormone action, distant physiologic
      regulation, and ductless secretion were once mysteries. They now form the basis
      of basic medical diagnostics and therapeutics. This article discusses and reviews
      the rich history that served as the foundation of modern medicine, from the early
      descriptions of tumors, to the discovery of hormones and assays, and how they
      resulted in the treatments available today.

PMID- 21095540
TI  - Pathology of gastrointestinal disorders.
AB  - Nonneoplastic and neoplastic proliferative lesions of endocrine cells of the
      gastrointestinal tract are detailed. A multistep continuum from hyperplasia,
      dysplasia to neoplasia is identified for histamine-producing enterochromaffin
      like (ECL) cells of the gastric corpus. Most gastric neuroendocrine tumors (NETs)
      are silent and composed by ECL cells, the second most frequent neuroendocrine
      neoplasms being the high-grade neuroendocrine carcinoma (NEC). In the duodenum,
      preneoplastic lesions are similarly described for gastrin (G) and somatostatin
      (D) cells. G-cell NETs are the most frequent neuroendocrine tumors of the
      duodenum, either functioning or nonfunctioning, followed by D-cell NETs and
      gangliocytic paraganglioma (GCP). No systematic definition of nonneoplastic
      lesions exists for endocrine cells of the ileum, appendix, and colon-rectum. The
      most frequent ileal NETs are serotonin-producing enterochromaffin (EC)-cell NETs
      (classic carcinoid), associating with functional syndrome only in presence of
      liver metastases. Neoplasms are usually larger in the colon as compared with the
      small lesions observed in the rectum. High-grade NECs are observed in the colon
      and rectum-sigmoid, often associate with nonendocrine neoplastic components, and
      fare an aggressive course with poor outcome and short survival.

PMID- 21095541
TI  - Appetite and hedonism: gut hormones and the brain.
AB  - Precise automatic control of food intake and energy expenditure maintains a
      steady weight and is fundamental to survival. The brainstem and hypothalamus are
      key areas within the brain that integrate peripheral signals from the gut and
      adipose tissue to control feeding behavior according to energy need. Gut hormones
      are released after a meal and signal to the brain to initiate meal termination
      and feelings of satiation. However, reward pathways are able to override this
      mechanism so that when palatable food is presented, food is consumed irrespective
      of energy requirements.

PMID- 21095542
TI  - Diabetic gastroparesis and its impact on glycemia.
AB  - Diabetes is the most common cause of gastroparesis and it is now recognized that
      the relationship between gastric emptying and glycemia is complex and
      intertwined. Postprandial blood glucose levels influence, and are influenced by,
      the rate of gastric emptying, highlighting the difficulty in determining which is
      the cause and which is the effect. Novel diagnostic techniques and therapeutic
      strategies have been developed for the management of diabetic gastroparesis. This
      article highlights recent advances in knowledge about diabetic gastroparesis,
      with an emphasis on the inter-relationships between disordered gastric motor
      function on glycemia and vice versa, as well as therapeutic strategies for
      optimizing glycemic control using modulation of gastric emptying.

PMID- 21095543
TI  - Harnessing the pancreatic stem cell.
AB  - Building on the elaborate research studies that have helped map out key decision
      points in the process of pancreas development, reprogramming of pluripotent
      embryonic stem cells or induced pluripotent stem cells offers the possibility of
      overcoming restrictions on tissue supply associated with transplantation of donor
      islets. In a healthy pancreas, the beta-cell mass can exhibit significant
      plasticity, as reflected in the normal adaptive response in beta-cell mass to
      offset the metabolic challenge associated with pregnancy and obesity. In this
      article, alternative strategies and potential sources of pancreatic stem cells
      are considered.

PMID- 21095544
TI  - Circulating biomarkers in neuroendocrine tumors of the enteropancreatic tract:
      application to diagnosis, monitoring disease, and as prognostic indicators.
AB  - Neuroendocrine tumors (NETs) are difficult to diagnose. Their symptoms may be
      vague or intermittent, and are frequently associated with much more common
      diseases; many of the tumors may be asymptomatic. Therefore, diagnosis can be
      delayed for some years. Because most NETs are secretory, the measurement of
      circulating biomarkers is helpful not only for diagnosis but also for assessing
      tumor response to treatment, monitoring disease progression, and use as
      prognostic indicators.

PMID- 21095545
TI  - Glucagonlike peptide-1 receptor: an example of translational research in
      insulinomas: a review.
AB  - Glucagonlike peptide-1 receptors (GLP-1R) play an increasingly important role in
      endocrine gastrointestinal tumor management. In particular, virtually all benign
      insulinomas express GLP-1R in high density. Exendin-4 is a GLP-1 analog that has
      a longer half-life than GLP-1. Targeting GLP-1R by (111)In-DOTA-exendin-4 or
      (111)In-DPTA-exendin-4 offers a new approach that permits the successful
      localization of small benign insulinomas. It is likely that this new noninvasive
      technique has the potential to replace the invasive localization by selective
      arterial stimulation and venous sampling.

PMID- 21095546
TI  - Signaling mechanisms in neuroendocrine tumors as targets for therapy.
AB  - Although neuroendocrine tumors are rare, the more common types such as
      gastrointestinal and pancreatic carcinoids, medullary thyroid cancers, and small
      cell lung cancers have been studied in detail during the last few years. Data
      published thus far indicate that multiple signaling pathways are involved in
      these cancers. Recent focus has been on developing novel therapeutics by
      targeting specific signaling pathways. This article details several of the
      signaling mechanisms that have been discovered to play a role in the development
      and progression of neuroendocrine tumors. The therapeutic options developed to
      address the various pathways, including their specific mechanisms of actions, are
      also discussed.

PMID- 21095547
TI  - Novel anticancer agents in clinical trials for well-differentiated neuroendocrine
      tumors.
AB  - Neuroendocrine tumors (NETs) are rare malignancies that arise from endocrine
      cells located in various anatomic locations, with a dramatic increase in
      incidence during the last 30 years. Limited therapeutic options are currently
      available for patients with advanced well-differentiated NETs, including
      carcinoids and pancreatic NETs. Streptozotocin-based chemotherapy and
      somatostatin analogues are drugs that are currently used for the treatment of
      progressive metastatic NETs. Recently, sunitinib demonstrating efficacy in
      pancreatic islet cell carcinomas has opened a new avenue for the treatment of
      NETs, and further trials shall be considered in NET types such as carcinoids,
      poorly differentiated neuroendocrine carcinomas, and several other endocrine
      tumors that depend on vascular endothelial growth factor (VEGF)/VEGF receptor for
      angiogenesis. In addition, drugs with distinct mechanisms of action, such as
      mammalian target of rapamycin inhibitors, currently investigated in phase 3
      trials, may also supply novel options to control tumor growth and metastasis.
      Although acknowledged as rare tumors, recent data demonstrated the feasibility of
      large randomized trials in this disease. Furthermore, data from large trials also
      showed the importance of selecting an appropriate patient population when
      designing randomized studies. This review focuses on novel therapeutic approaches
      in the treatment of well-differentiated NETs. Based on recent data, novel
      strategies may now be designed using those anticancer agents to optimize the
      current treatment of patients with NETs.

PMID- 21095548
TI  - Nutrition and gastroenteropancreatic neuroendocrine tumors.
AB  - Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are relatively rare
      neoplasms that characteristically synthesize and secrete an excess of a variety
      of regulatory peptides, hormones, and neuroamines, which regulate gut and
      pancreatic function. This excess can lead to distinct clinical syndromes.
      Therapeutic strategies include surgery, radiofrequency ablation, chemotherapy,
      chemoembolization, and biotherapy using somatostatin analogs. The clinical
      syndromes and the various management strategies can lead to altered gut and
      pancreatic function with nutritional consequences. Diet and nutritional
      management is critical for GEP NET patients and is the focus of this article.

PMID- 21095549
TI  - The role of angiogenesis in neuroendocrine tumors.
AB  - The first studies to assess in vitro angiogenesis in neuroendocrine tumors used
      animal-based assays to study the antiangiogenic properties of somatostatin
      analogs. Current technologies enable investigators to directly appraise the in
      vitro angiogenic response of an individual's neuroendocrine tumor with and
      without potential antiangiogenic reagents. This article describes the evolution
      of methods to assess in vitro angiogenesis in neuroendocrine tumors and describes
      some of the clinical data.

PMID- 21095550
TI  - Preface: human response: health promotion and healing before, during, and after
      catastrophic events.

PMID- 21095551
TI  - Disaster nursing: a retrospective review.
AB  - A plethora of information exists in the literature regarding emergencies and
      disasters. Nevertheless, significant gaps in the science related to nurses
      working during disasters are revealed. Few studies have addressed the perspective
      of nurses and their intent to respond to future disasters. Because nurses are
      invaluable to disaster response efforts, more research is essential to validate
      current findings and elucidate the needs of nurses who respond to disasters and
      other health emergencies. There is a paucity of research in the literature
      describing nurses' lived experiences of working during hurricanes. Natural
      disasters inevitably inflict human suffering, and nurses are expected to respond
      and provide services during these catastrophic times. Lost within this
      expectation are the experiences and concerns of the nurses who are called upon
      and intend to respond to the disaster, and yet are themselves affected by the
      disaster. Understanding the experiences and needs of nurses who decide to respond
      to the call of duty and work during disasters remains unclear in the literature.
      Research in the area of disaster response intentions by nurses becomes the
      initial step in understanding the phenomenon of working during a disaster and
      creating innovative approaches that address working during disasters. Disaster
      policies have been developed and implemented at the international, national,
      state, local, and hospital level. Nevertheless, disasters continue to adversely
      impact communities and hospitals at all levels causing injuries, death, and
      destruction of infrastructure. To reduce the impact of disasters, continued
      research is needed to inform and strengthen future disaster policies. Knowledge
      gained from future research has great potential to inform nursing education,
      research, and practice, as well as health policy related to the care of
      individuals and responders before, during, and after disasters.

PMID- 21095552
TI  - Financial and economic considerations for emergency response providers.
AB  - Catastrophic events often threaten or cause depletion of resources. It is
      generally accepted that changes inherent to disasters are stressful. The
      Conservation of Resources Theory predicts that positive and negative changes in
      resources will have markedly different effects.28 This theory proposes that
      resource losses are psychologically stressful, whereas resource gains buffer
      against the effects of resource loss. For first responders, the level of
      preparedness is crucial. Investments in planning, training, and logistics are
      necessary to mitigate the stress associated with a crisis. Stress is also related
      to not knowing the future of their loved ones if death or permanent incapacity
      occurs, hence specific laws and financial resources provide a safety net to
      dependents of first responders and survivors. This kind of safety gives the first
      responders peace of mind and assurance that the future of their dependents will
      not be jeopardized. Incentives that are offered let the first responders know
      that they are valued and appreciated. Indeed, financial support considerably
      helps first responders before, during, and after catastrophic events. It assists
      them to cope with stress at the individual level and allows them to become more
      resilient; this resonates to the community and country in which they serve and
      enhances their potential to save lives and prevent disabilities.

PMID- 21095553
TI  - Physical and environmental considerations for first responders.
AB  - To prioritize the most common effects of a disaster, HCPs must decide in advance
      what is needed and how, when, and whom to provide the necessary support to deal
      with the posteffects of a disaster. During the rescue mission, the primary public
      health concern is clean drinking water, food, shelter, and medical care. Medical
      care is critical especially in areas where little or no medical care exists.
      Natural disasters do not necessarily cause an increase in infectious disease
      outbreaks. However, contaminated water and food supplies as well as the lack of
      shelter and medical care may have a secondary effect of worsening illnesses that
      already exists in the affected region. Appropriate preparation in the form of
      preplanning for immunizations as well as education about other forms of
      protection, such as appropriate apparel and water decontamination, promotes a
      safer environment for first responders and survivors. The continued need for
      postdisaster health monitoring for HCPs is imperative. The effects of a disaster
      last a long time; therefore there is an ongoing need to focus on the physical and
      environmental effects, including surveying and monitoring for infectious water or
      insect-transmitted diseases; restoring normal primary health services, water
      systems, transportation, housing, and employment; and continuing to assist the
      community's recovery after the immediate crisis has subsided.

PMID- 21095554
TI  - Cultural, ethical, and spiritual competencies of health care providers responding
      to a catastrophic event.
AB  - Compassion is a language that is understood across cultures, religions, and
      nations. Being compassionate and empathetic is a basic responsibility of health
      care providers responding to disasters. Compassion and empathy cannot be
      operationalized unless providers show culturally competent, ethically right, and
      spiritually caring behavior. In addition to being accepting of cultures other
      than their own, providers must read literature and familiarize themselves with
      the predominant cultures of the affected population. Ethically right decision
      making is essentially an act of balancing the risks and benefits to the entire
      society. Spiritual care is an important dimension of total health, and therefore
      recognition and resolution of the spiritual needs of disaster victims is an
      essential role of health care providers. Disaster management is teamwork and
      therefore requires that health care providers draw on the expertise and support
      of other team members; coordinating efforts with local religious, social
      governmental organizations, and NGOs to deal with the intangible effects of the
      cultural and spiritual impact of a disaster and to prevent further demoralization
      of the affected community is imperative. Disasters occur, and the only thing that
      can ameliorate their devastating effects is to improve disaster preparedness and
      respond collectively and courageously to every catastrophic event.

PMID- 21095556
TI  - Responding to the psychosocial needs of children and families in disasters.
AB  - Pediatric health care professionals play a critical role in disaster response by
      assisting parents, teachers, and health care organizations to meet the unique
      needs of children, adolescents, and families during all phases of disaster.
      Addressing the psychosocial needs of this vulnerable population by providing age
      appropriate care and facilitating adaptive coping strategies has the potential to
      decrease the long-term behavioral health consequences and help children
      positively adjust to a stressful life experience.

PMID- 21095555
TI  - Keeping PEDIATRICS in pediatric disaster management: Before, during, and in the
      aftermath of complex emergencies.
AB  - From 1900 there have been more than 9800 natural disasters affecting more than 67
      million children worldwide. Because of unique physical, developmental, and
      psychosocial characteristics of children, caring for them during complex
      emergencies is different to caring for adults. However, planning for these unique
      physical, developmental, and psychosocial needs has not been well addressed when
      planning for complex emergencies. Therefore, the purpose of this article is to
      review those characteristics of children that place them at higher disaster risk,
      and discuss the preparations necessary to meet their needs before, during, and in
      the aftermath of complex emergencies.

PMID- 21095557
TI  - Disaster planning for vulnerable populations: mental health.
AB  - Psychological responses to a disaster are well established; however, little is
      known regarding how individuals with established psychiatric and mental health
      needs respond to a disaster. Further research is needed to provide a better
      understanding as well as to provide data and information that would assist in the
      provision of timely and adequate intervention and treatment. Addressing the
      psychological and psychiatric needs of this vulnerable population would assist in
      the provision of adequate and appropriate psychiatric mental health care in a
      timely and an effective manner.

PMID- 21095558
TI  - Catastrophic events and older adults.
AB  - The plight of older adults during catastrophic events is a societal concern.
      Older persons have an increased prevalence of cognitive disorders, chronic
      illnesses, and mobility problems that limit their ability to cope. These
      disorders may result in a lack of mental capacity and the ability to discern when
      they should evacuate or resolve problems encountered during a catastrophe. Some
      older persons may have limited transportation options, and many of the elderly
      survivors are at increased risk for abuse, neglect, and exploitation.
      Recommendations for future catastrophic events include the development of a
      federal tracking system for elders and other vulnerable adults, the designation
      of separate shelter areas for elders and other vulnerable adults, and involvement
      of gerontological professionals in all aspects of emergency preparedness and care
      delivery, including training of frontline workers. Preparation through preevent
      planning that includes region-specific social services, medical and public health
      resources, volunteers, and facilities for elders and vulnerable adults is
      critical. Elders need to be protected from abuse and fraud during catastrophic
      events. A public health triage system for elders and other vulnerable populations
      in pre- and postdisaster situations is useful, and disaster preparedness is
      paramount. Communities and members of safety and rescue teams must address
      ethical issues before an event. When older adults are involved, consideration
      needs to be given to triage decision making, transporting those who are immobile,
      the care of older adults who receive palliative care, and the equitable
      distribution of resources. Nurses are perfectly equipped with the skills,
      knowledge, and training needed to plan and implement disaster preparedness
      programs. In keeping with the tradition of Florence Nightingale, nurses can
      assume several crucial roles in disaster preparedness for older adults. Nurses
      possess the ability to participate and lead community policy development, serve
      on rescue teams, perform patient assessments, and deliver care. Nurses are
      crucial to well-planned and executed programs for catastrophic events that affect
      older adults. Also, all health care providers involved must be aware of the
      physical and psychological ramifications of disaster relief. The health and
      resilience of disaster-relief teams depend on paying attention to signs and
      symptoms of posttraumatic stress disorder and seeking appropriate treatment
      should it occur.

PMID- 21095559
TI  - Cultural, ethical, and spiritual implications of natural disasters from the
      survivors' perspective.
AB  - Cultural, ethical, and spiritual implications of disaster depend on various
      factors. The impact of a disaster on a particular culture depends on the people
      in that culture and the strength and resilience of the culture. Disasters may
      slow cultural development; however, typically the customs, beliefs, and value
      systems remain the same even if the outward expressions of culture change.
      Critical to survivors is the implication of aid that is culturally sensitive.
      Ethical questions and dilemmas associated with disasters and their management are
      profound. Adhering to ethical principles does not solve all of the issues related
      to disaster management, but awareness of their utility is important. People
      affected by a disaster may not be capable of responding to human rights
      violations, so it is the first responders who must be cognizant of their
      responsibility to protect the victims' dignity and rights. Ethical treatment of
      survivors entails a crucial blend of knowledge about ethnic culture, religious
      beliefs, and human rights. A strong awareness of ethical principles is merely a
      beginning step to well-informed decision making in disaster situations. The
      literature also suggests that during a crisis, spirituality helps victims to
      cope. Important to any catastrophic event is the understanding that every
      disaster creates unique circumstances that require relief responses tailored to
      the specific situation.

PMID- 21095560
TI  - Disaster aftermath: a first-person perspective as a responder and caregiver.
AB  - The patient reception team remains in existence, although its services have not
      been called upon since Hurricane Katrina. Drills are held, largely for ancillary
      personnel, with providers brought in on an as-needed basis. The team stands ready
      for the next challenge, knowing that the most important lesson is to expect the
      unexpected. Responders, who understand this and take it to heart, from the onset
      of the mitigation phase through to the final recovery phase, should find
      themselves better able to surmount the challenges they will surely face.

PMID- 21095561
TI  - CellBio-X: celebrating the interface between Cell Biology and other disciplines.

PMID- 21095562
TI  - Probing the proteostasis network.

PMID- 21095563
TI  - Disarming Clostridium difficile.
AB  - In this issue, Puriet al. (2010) present inhibitors that prevent the
      autocatalytic activation of the clostridial toxin TcdB in vivo. Their approach is
      likely to provide guidance for the development of novel drugs targeting virulence
      factors and thereby rendering bacterial pathogens innocuous.

PMID- 21095564
TI  - Reeling in the catch: advancing cleavable linkers for proteomics.
AB  - In global proteomic applications that focus on the characterization of proteins
      that have been derivatized using bioorthogonal chemistry, a challenge persists in
      the release of labeled proteins from supports used for purification. In this
      issue, Yang and coworkers (2010) present a detailed study of the diazobenzene
      cleavable linker system as an effective solution for proteomic studies.

PMID- 21095565
TI  - Making E. coli an erythromycin production plant.
AB  - The production of bioactive compounds in heterologous hosts has become a valuable
      tool for the investigation of biosynthetic pathways and their rational
      engineering. In this issue of Chemistry & Biology, Zhang et al. (2010) report the
      manipulation of E. coli for the production of erythromycin A.

PMID- 21095566
TI  - Assembling ligands in situ using bioorthogonal boronate ester synthesis.
AB  - Many molecules that could manipulate cellular function are not practical due to
      their large size and concomitant undesirable pharmocokinetic properties. Here, we
      describe a bioorthogonal, highly stable boronate ester (HiSBE) synthesis and use
      this reaction to synthesize a biologically active molecule from smaller
      precursors in a physiological context. The rapid rate of HiSBE synthesis suggests
      that it may be useful for assembling a wide variety of biologically active
      molecules in physiological solutions.

PMID- 21095567
TI  - Chemical-genetic screen identifies riluzole as an enhancer of Wnt/beta-catenin
      signaling in melanoma.
AB  - To identify new protein and pharmacological regulators of Wnt/beta-catenin
      signaling, we used a cell-based reporter assay to screen a collection of 1857
      human-experienced compounds for their ability to enhance activation of the beta
      catenin reporter by a low concentration of WNT3A. This identified 44 unique
      compounds, including the FDA-approved drug riluzole, which is presently in
      clinical trials for treating melanoma. We found that treating melanoma cells with
      riluzole in vitro enhances the ability of WNT3A to regulate gene expression, to
      promote pigmentation, and to decrease cell proliferation. Furthermore riluzole,
      like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs
      targeting the metabotropic glutamate receptor, GRM1, a reported indirect target
      of riluzole, enhance beta-catenin signaling. The unexpected regulation of beta
      catenin signaling by both riluzole and GRM1 has implications for the future uses
      of this drug.

PMID- 21095568
TI  - Allele-selective inhibition of huntingtin expression by switching to an miRNA
      like RNAi mechanism.
AB  - Inhibiting expression of huntingtin (HTT) protein is a promising strategy for
      treating Huntington's disease (HD), but indiscriminant inhibition of both wild
      type and mutant alleles may lead to toxicity. An ideal silencing agent would
      block expression of mutant HTT while leaving expression of wild-type HTT intact.
      We observe that fully complementary duplex RNAs targeting the expanded CAG repeat
      within HTT mRNA block expression of both alleles. Switching the RNAi mechanism
      toward that used by miRNAs by introducing one or more mismatched bases into these
      duplex RNAs leads to potent (<10 nM) and highly selective (>30-fold relative to
      wild-type HTT) inhibition of mutant HTT expression in patient-derived cells.
      Potent, allele selective inhibition of HTT by mismatched RNAs provides a new
      option for developing HD therapeutics.

PMID- 21095569
TI  - Identification and evaluation of small molecule pan-caspase inhibitors in
      Huntington's disease models.
AB  - Huntington's Disease (HD) is characterized by a mutation in the huntingtin (Htt)
      gene encoding an expansion of glutamine repeats on the N terminus of the Htt
      protein. Numerous studies have identified Htt proteolysis as a critical
      pathological event in HD postmortem human tissue and mouse HD models, and
      proteases known as caspases have emerged as attractive HD therapeutic targets. We
      report the use of the substrate activity screening method against caspase-3 and 
      6 to identify three novel, pan-caspase inhibitors that block proteolysis of Htt
      at caspase-3 and -6 cleavage sites. In HD models these irreversible inhibitors
      suppressed Hdh(111Q/111Q)-mediated toxicity and rescued rat striatal and cortical
      neurons from cell death. In this study, the identified nonpeptidic caspase
      inhibitors were used to confirm the role of caspase-mediated Htt proteolysis in
      HD. These results further implicate caspases as promising targets for HD
      therapeutic development.

PMID- 21095570
TI  - Rational design of inhibitors and activity-based probes targeting Clostridium
      difficile virulence factor TcdB.
AB  - Clostridium difficile is a leading cause of nosocomial infections. The major
      virulence factors of this pathogen are the multi-domain toxins TcdA and TcdB.
      These toxins contain a cysteine protease domain (CPD) that autoproteolytically
      releases a cytotoxic effector domain upon binding intracellular inositol
      hexakisphosphate. Currently, there are no known inhibitors of this protease.
      Here, we describe the rational design of covalent small molecule inhibitors of
      TcdB CPD. We identified compounds that inactivate TcdB holotoxin function in
      cells and solved the structure of inhibitor-bound protease to 2.0 A. This
      structure reveals the molecular basis of CPD substrate recognition and informed
      the synthesis of activity-based probes for this enzyme. The inhibitors presented
      will guide the development of therapeutics targeting C. difficile, and the probes
      will serve as tools for studying the unique activation mechanism of bacterial
      toxin CPDs.

PMID- 21095571
TI  - Comparative analysis of cleavable azobenzene-based affinity tags for
      bioorthogonal chemical proteomics.
AB  - The advances in bioorthogonal ligation methods have provided new opportunities
      for proteomic analysis of newly synthesized proteins, posttranslational
      modifications, and specific enzyme families using azide/alkyne-functionalized
      chemical reporters and activity-based probes. Efficient enrichment and elution of
      azide/alkyne-labeled proteins with selectively cleavable affinity tags are
      essential for protein identification and quantification applications. Here, we
      report the synthesis and comparative analysis of Na2S2O4-cleavable azobenzene
      based affinity tags for bioorthogonal chemical proteomics. We demonstrated that
      ortho-hydroxyl substituent is required for efficient azobenzene-bond cleavage and
      show that these cleavable affinity tags can be used to identify newly synthesized
      proteins in bacteria targeted by amino acid chemical reporters as well as their
      sites of modification on endogenously expressed proteins. The azobenzene-based
      affinity tags are compatible with in-gel, in-solution, and on-bead enrichment
      strategies and should afford useful tools for diverse bioorthogonal proteomic
      applications.

PMID- 21095573
TI  - Complete biosynthesis of erythromycin A and designed analogs using E. coli as a
      heterologous host.
AB  - Erythromycin A is a potent antibiotic long-recognized as a therapeutic option for
      bacterial infections. The soil-dwelling bacterium Saccharopolyspora erythraea
      natively produces erythromycin A from a 55 kb gene cluster composed of three
      large polyketide synthase genes (each ~10 kb) and 17 additional genes responsible
      for deoxysugar biosynthesis, macrolide tailoring, and resistance. In this study,
      the erythromycin A gene cluster was systematically transferred from S. erythraea
      to E. coli for reconstituted biosynthesis, with titers reaching 10 mg/l.
      Polyketide biosynthesis was then modified to allow the production of two
      erythromycin analogs. Success establishes E. coli as a viable option for the
      heterologous production of erythromycin A and more broadly as a platform for the
      directed production of erythromycin analogs.

PMID- 21095572
TI  - Broad-spectrum antibiotic activity of the arylomycin natural products is masked
      by natural target mutations.
AB  - Novel classes of broad-spectrum antibiotics are needed to treat multidrug
      resistant pathogens. The arylomycin class of natural products inhibits a
      promising antimicrobial target, type I signal peptidase (SPase), but upon initial
      characterization appeared to lack whole-cell activity against most pathogens.
      Here, we show that Staphylococcus epidermidis, which is sensitive to the
      arylomycins, evolves resistance via mutations in SPase and that analogous
      mutations are responsible for the natural resistance of Staphylococcus aureus,
      Escherichia coli, and Pseudomonas aeruginosa. We identify diverse bacteria
      lacking these mutations and demonstrate that most are sensitive to the
      arylomycins. The results illustrate that the arylomycins have a broad-spectrum of
      activity and are viable candidates for development into therapeutics. The results
      also raise the possibility that naturally occurring resistance may have masked
      other natural product scaffolds that might be developed into therapeutics.

PMID- 21095574
TI  - Activation state-dependent binding of small molecule kinase inhibitors:
      structural insights from biochemistry.
AB  - Interactions between kinases and small molecule inhibitors can be activation
      state dependent. A detailed understanding of inhibitor binding therefore requires
      characterizing interactions across multiple activation states. We have
      systematically explored the effects of ABL1 activation loop phosphorylation and
      PDGFR family autoinhibitory juxtamembrane domain docking on inhibitor binding
      affinity. For a diverse compound set, the affinity patterns correctly classify
      inhibitors as having type I or type II binding modes, and we show that
      juxtamembrane domain docking can have dramatic negative effects on inhibitor
      affinity. The results have allowed us to associate ligand-induced conformational
      changes observed in cocrystal structures with specific energetic costs. The
      approach we describe enables investigation of the complex relationship between
      kinase activation state and compound binding affinity and should facilitate
      strategic inhibitor design.

PMID- 21095575
TI  - Cell-penetrant, nanomolar O-GlcNAcase inhibitors selective against lysosomal
      hexosaminidases.
AB  - Posttranslational modification of metazoan nucleocytoplasmic proteins with N
      acetylglucosamine (O-GlcNAc) is essential, dynamic, and inducible and can compete
      with protein phosphorylation in signal transduction. Inhibitors of O-GlcNAcase,
      the enzyme removing O-GlcNAc, are useful tools for studying the role of O-GlcNAc
      in a range of cellular processes. We report the discovery of nanomolar OGA
      inhibitors that are up to 900,000-fold selective over the related lysosomal
      hexosaminidases. When applied at nanomolar concentrations on live cells, these
      cell-penetrant molecules shift the O-GlcNAc equilibrium toward hyper-O
      GlcNAcylation with EC50 values down to 3 nM and are thus invaluable tools for the
      study of O-GlcNAc cell biology.

PMID- 21095577
TI  - The role of biomarkers in respiratory disease.

PMID- 21095576
TI  - Inhibitor of fatty acid amide hydrolase normalizes cardiovascular function in
      hypertension without adverse metabolic effects.
AB  - The enzyme fatty acid amide hydrolase (FAAH) catalyzes the in vivo degradation of
      the endocannabinoid anandamide, thus controlling its action at receptors. A novel
      FAAH inhibitor, AM3506, normalizes the elevated blood pressure and cardiac
      contractility of spontaneously hypertensive rats (SHR) without affecting these
      parameters in normotensive rats. These effects are due to blockade of FAAH and a
      corresponding rise in brain anandamide levels, resulting in CB1 receptor-mediated
      decrease in sympathetic tone. The supersensitivity of SHR to CB1 receptor
      mediated cardiovascular depression is related to increased G protein coupling of
      CB1 receptors. Importantly, AM3506 does not elicit hyperglycemia and insulin
      resistance seen with other FAAH inhibitors or in FAAH-/- mice, which is related
      to its inability to inhibit FAAH in the liver due to rapid hepatic uptake and
      metabolism. This unique activity profile offers improved therapeutic value in
      hypertension.

PMID- 21095578
TI  - ATM: Promoter of metabolic "cost" reduction and "savings" usage during hypoxia
      through mTORC1 regulation.
AB  - Cells must sense environmental conditions and adjust to maintain metabolic
      homeostasis and survive stress conditions; in this issue, Cam et al. (2010) show
      that the tumor suppressor kinase ATM is activated by hypoxia, phosphorylates and
      stabilizes HIF-1alpha, and inhibits mTORC1.

PMID- 21095579
TI  - A pause to splice.
AB  - Maturation of mRNA termini occurs during transcription and can be aided by
      pausing of RNA polymerase II (RNAPII). In this issue of Molecular Cell, two
      groups now demonstrate that RNAPII pausing may also assist cotranscriptional
      splicing in S. cerevisiae.

PMID- 21095580
TI  - Choreography of the 9-1-1 checkpoint complex: DDK puts a check on the
      checkpoints.
AB  - Checkpoint proteins respond to DNA damage by halting the cell cycle until the
      damage is repaired. In this issue of Molecular Cell, Furuya et al. (2010) provide
      evidence that checkpoint proteins need to be removed from sites of damage in
      order to properly repair it.

PMID- 21095581
TI  - The meaning of pausing.
AB  - Pausing of RNA polymerase II (RNAPII) at the 5' end of genes is a widespread
      phenomenon in metazoans, but the role of this event in gene regulation is poorly
      understood. Gilchrist et al. (2010) now demonstrate that RNAPII pausing
      counteracts DNA-influenced nucleosome organization to allow precise gene
      activation.

PMID- 21095583
TI  - PARP-1 attenuates Smad-mediated transcription.
AB  - The versatile cytokine transforming growth factor beta (TGF-beta) regulates
      cellular growth, differentiation, and migration during embryonic development and
      adult tissue homeostasis. Activation of TGF-beta receptors leads to
      phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate
      in the nucleus where they recognize gene regulatory regions and orchestrate
      transcription. Termination of Smad-activated transcription involves Smad
      dephosphorylation, nuclear export, or ubiquitin-mediated degradation. In an
      unbiased proteomic screen, we identified poly(ADP-ribose) polymerase-1 (PARP-1)
      as a Smad-interacting partner. PARP-1 dissociates Smad complexes from DNA by ADP
      ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and
      TGF-beta-induced epithelial-mesenchymal transition. Thus, our results identify
      ADP-ribosylation of Smad proteins by PARP-1 as a key step in controlling the
      strength and duration of Smad-mediated transcription.

PMID- 21095582
TI  - mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent
      phosphorylation of HIF-1alpha.
AB  - The mTOR complex-1 (mTORC1) coordinates cell growth and metabolism, acting as a
      restriction point under stress conditions such as low oxygen tension (hypoxia).
      Hypoxia suppresses mTORC1 signaling. However, the signals by which hypoxia
      suppresses mTORC1 are only partially understood, and a direct link between
      hypoxia-driven physiological stress and the regulation of mTORC1 signaling is
      unknown. Here we show that hypoxia results in ataxia telangiectasia mutated (ATM)
      dependent phosphorylation of hypoxia-inducible factor 1-alpha (HIF-1alpha) on
      serine(696) and mediates downregulation of mTORC1 signaling. Deregulation of
      these pathways in pediatric solid tumor xenografts suggests a link between mTORC1
      dysregulation and solid tumor development and points to an important role for
      hypoxic regulation of mTORC1 activity in tumor development.

PMID- 21095584
TI  - Primary cilium-dependent and -independent Hedgehog signaling inhibits p16(INK4A).
AB  - In a genome-wide siRNA analysis of p16(INK4a) (p16) modulators, we identify the
      Hedgehog (Hh) pathway component SUFU and formally demonstrate that Hh signaling
      promotes mitogenesis by suppression of p16. A fragment of the Hh-responsive GLI2
      transcription factor directly binds and inhibits the p16 promoter and senescence
      is associated with the loss of nuclear GLI2. Hh components partially reside in
      the primary cilium (PC), and the small fraction of cells in mass culture that
      elaborate a PC have the lowest expression of p16. Suppression of p16 is effected
      by both PC-dependent and -independent routes, and ablation of p16 renders cells
      insensitive to an Hh inhibitor and increases PC formation. These results directly
      link a well-established developmental mitogenic pathway with a key tumor
      suppressor and contribute to the molecular understanding of replicative
      senescence, Hh-mediated oncogenesis, and potentially the role of p16 in aging.

PMID- 21095585
TI  - Ubiquitin binding to A20 ZnF4 is required for modulation of NF-kappaB signaling.
AB  - Inactivating mutations in the ubiquitin (Ub) editing protein A20 promote
      persistent nuclear factor (NF)-kappaB signaling and are genetically linked to
      inflammatory diseases and hematologic cancers. A20 tightly regulates NF-kappaB
      signaling by acting as an Ub editor, removing K63-linked Ub chains and mediating
      addition of Ub chains that target substrates for degradation. However, a precise
      molecular understanding of how A20 modulates this pathway remains elusive. Here,
      using structural analysis, domain mapping, and functional assays, we show that
      A20 zinc finger 4 (ZnF4) does not directly interact with E2 enzymes but instead
      can bind mono-Ub and K63-linked poly-Ub. Mutations to the A20 ZnF4 Ub-binding
      surface result in decreased A20-mediated ubiquitination and impaired regulation
      of NF-kappaB signaling. Collectively, our studies illuminate the mechanistically
      distinct but biologically interdependent activities of the A20 ZnF and ovarian
      tumor (OTU) domains that are inherent to the Ub editing process and, ultimately,
      to regulation of NF-kappaB signaling.

PMID- 21095586
TI  - Pervasive and cooperative deadenylation of 3'UTRs by embryonic microRNA families.
AB  - To understand how miRNA-mediated silencing impacts on embryonic mRNAs, we
      conducted a functional survey of abundant maternal and zygotic miRNA families in
      the C. elegans embryo. We show that the miR-35-42 and the miR-51-56 miRNA
      families define maternal and zygotic miRNA-induced silencing complexes (miRISCs),
      respectively, that share a large number of components. Using a cell-free C.
      elegans embryonic extract, we demonstrate that the miRISC directs the rapid
      deadenylation of reporter mRNAs with natural 3'UTRs. The deadenylated targets are
      translationally suppressed and remarkably stable. Sampling of the predicted miR
      35-42 targets reveals that roughly half are deadenylated in a miRNA-dependent
      manner, but with each target displaying a distinct efficiency and pattern of
      deadenylation. Finally, we demonstrate that functional cooperation between
      distinct miRISCs within 3'UTRs is required to potentiate deadenylation. With this
      report, we reveal the extensive and direct impact of miRNA-mediated deadenylation
      on embryonic mRNAs.

PMID- 21095587
TI  - Global analysis of nascent RNA reveals transcriptional pausing in terminal exons.
AB  - Pre-mRNA splicing is catalyzed by the spliceosome, which can assemble on pre-mRNA
      cotranscriptionally. However, whether splicing generally occurs during
      transcription has not been addressed. Indeed, splicing catalysis is expected to
      occur posttranscriptionally in yeast, where the shortness of terminal exons
      should leave insufficient time for splicing. Here, we isolate endogenous S.
      cerevisiae nascent RNA and determine gene-specific splicing efficiencies and
      transcription profiles, using high-density tiling microarrays. Surprisingly, we
      find that splicing occurs cotranscriptionally for the majority of intron
      containing genes. Analysis of transcription profiles reveals Pol II pausing
      within the terminal exons of these genes. Intronless and inefficiently spliced
      genes lack this pause. In silico simulations of transcription and splicing
      kinetics confirm that this pausing event provides sufficient time for splicing
      before termination. The discovery of terminal exon pausing demonstrates
      functional coupling of transcription and splicing near gene ends.

PMID- 21095588
TI  - Splicing-dependent RNA polymerase pausing in yeast.
AB  - In eukaryotic cells, there is evidence for functional coupling between
      transcription and processing of pre-mRNAs. To better understand this coupling, we
      performed a high-resolution kinetic analysis of transcription and splicing in
      budding yeast. This revealed that shortly after induction of transcription, RNA
      polymerase accumulates transiently around the 3' end of the intron on two
      reporter genes. This apparent transcriptional pause coincides with splicing
      factor recruitment and with the first detection of spliced mRNA and is repeated
      periodically thereafter. Pausing requires productive splicing, as it is lost upon
      mutation of the intron and restored by suppressing the splicing defect. The
      carboxy-terminal domain of the paused polymerase large subunit is
      hyperphosphorylated on serine 5, and phosphorylation of serine 2 is first
      detected here. Phosphorylated polymerase also accumulates around the 3' splice
      sites of constitutively expressed, endogenous yeast genes. We propose that
      transcriptional pausing is imposed by a checkpoint associated with
      cotranscriptional splicing.

PMID- 21095589
TI  - Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to
      regulate T-box family member-dependent gene expression.
AB  - The stable and heritable H3K27-methyl mark suppresses transcription of lineage
      specific genes in progenitor cells. During developmental transitions, histone
      demethylases are required to dramatically alter epigenetic and gene expression
      states to create new cell-specific profiles. It is unclear why demethylase
      proteins that antagonize polycomb-mediated repression continue to be expressed in
      terminally differentiated cells where further changes in H3K27 methylation could
      be deleterious. In this study, we show that the H3K27 demethylases, Jmjd3 and
      UTX, mediate a functional interaction between the lineage-defining T-box
      transcription factor family and a Brg1-containing SWI/SNF remodeling complex.
      Importantly, Jmjd3 is required for the coprecipitation of Brg1 with the T-box
      factor, T-bet, and this interaction is necessary for Ifng remodeling in
      differentiated Th1 cells. Thus, Jmjd3 has a required role in general chromatin
      remodeling that is independent from its H3K27 demethylase potential. This
      function for H3K27 demethylase proteins may explain their presence in
      differentiated cells where the epigenetic profile is already established.

PMID- 21095590
TI  - DDK phosphorylates checkpoint clamp component Rad9 and promotes its release from
      damaged chromatin.
AB  - When inappropriate DNA structures arise, they are sensed by DNA structure
      dependent checkpoint pathways and subsequently repaired. Recruitment of
      checkpoint proteins to such structures precedes recruitment of proteins involved
      in DNA metabolism. Thus, checkpoints can regulate DNA metabolism. We show that
      fission yeast Rad9, a 9-1-1 heterotrimeric checkpoint-clamp component, is
      phosphorylated by Hsk1(Cdc7), the Schizosaccharomyces pombe Dbf4-dependent kinase
      (DDK) homolog, in response to replication-induced DNA damage. Phosphorylation of
      Rad9 disrupts its interaction with replication protein A (RPA) and is dependent
      on 9-1-1 chromatin loading, the Rad9-associated protein Rad4/Cut5(TopBP1), and
      prior phosphorylation by Rad3(ATR). rad9 mutants defective in DDK phosphorylation
      show wild-type checkpoint responses but abnormal DNA repair protein foci and
      decreased viability after replication stress. We propose that Rad9
      phosphorylation by DDK releases Rad9 from DNA damage sites to facilitate DNA
      repair.

PMID- 21095591
TI  - Crystal structures of RNase H2 in complex with nucleic acid reveal the mechanism
      of RNA-DNA junction recognition and cleavage.
AB  - Two classes of RNase H hydrolyze RNA of RNA/DNA hybrids. In contrast to RNase H1
      that requires four ribonucleotides for cleavage, RNase H2 can nick duplex DNAs
      containing a single ribonucleotide, suggesting different in vivo substrates. We
      report here the crystal structures of a type 2 RNase H in complex with substrates
      containing a (5')RNA-DNA(3') junction. They revealed a unique mechanism of
      recognition and substrate-assisted cleavage. A conserved tyrosine residue
      distorts the nucleic acid at the junction, allowing the substrate to function in
      catalysis by participating in coordination of the active site metal ion. The
      biochemical and structural properties of RNase H2 explain the preference of the
      enzyme for junction substrates and establish the structural and mechanistic
      differences with RNase H1. Junction recognition is important for the removal of
      RNA embedded in DNA and may play an important role in DNA replication and repair.

PMID- 21095593
TI  - [Psychosocial and spiritual experience of elderly people recovering from stroke].

PMID- 21095592
TI  - ATP-dependent steps in the binding of ubiquitin conjugates to the 26S proteasome
      that commit to degradation.
AB  - Eukaryotic cells target proteins for degradation by the 26S proteasome by
      attaching a ubiquitin chain. Using a rapid assay, we analyzed the initial binding
      of ubiquitinated proteins to purified 26S particles as an isolated process at 4
      degrees C. Subunits Rpn10 and Rpn13 contribute equally to the high-affinity
      binding of ubiquitin chains, but in their absence, ubiquitin conjugates bind to
      another site with 4-fold lower affinity. Conjugate binding is stimulated 2- to 4
      fold by binding of ATP or the nonhydrolyzable analog, ATPgammaS (but not ADP), to
      the 19S ATPases. Following this initial, reversible association, ubiquitin
      conjugates at 37 degrees C become more tightly bound through a step that requires
      ATP hydrolysis and a loosely folded domain on the protein, but appears
      independent of ubiquitin. Unfolded or loosely folded polypeptides can inhibit
      this tighter binding. This commitment step precedes substrate deubiquitination
      and allows for selection of ubiquitinated proteins capable of being unfolded and
      efficiently degraded.

PMID- 21095594
TI  - Farewell to editorial board member.

PMID- 21095595
TI  - Education changes Mexican nurses' knowledge and attitudes regarding pediatric
      pain.
AB  - This study explored the effectiveness of a pain education intervention on Mexican
      nurses' knowledge and attitudes toward pediatric pain. A convenience sample of
      106 registered nurses from three hospitals in Mexico City was recruited. A
      Pediatric Pain Education Program (PPEP) was developed, implemented, and evaluated
      by a nurse researcher, clinical nurse specialist, and a child life specialist.
      The 4-hour program, which was translated into Spanish, consisted of pain
      assessment, physiology, and management, including pharmacology and
      nonpharmacology. The effects of PPEP were measured in a one-group pretest
      posttest design using a translated Spanish version of the Pediatric Nurses'
      Knowledge and Attitudes Survey (PNKAS). A total of 79 nurses completed both
      tests. A paired t test indicated significant differences between pre- and
      posttest results (p < .0001) on the PNKAS. The hospital site and years of nursing
      experience were significantly related to nurses' pre- and post-PNKAS scores. One
      test item on children's ability to reliably report their pain had a significantly
      lower score after the intervention (p = .016). The intervention was effective in
      improving Mexican pediatric nurses' knowledge and attitudes. However, it is not
      known how long this effect was maintained. Health care professionals can share a
      common vision for pain management by increasing international collaborative
      efforts and by advancing pediatric pain knowledge.

PMID- 21095596
TI  - Literature review of pain prevalence among older residents of nursing homes.
AB  - Pain is a common symptom among older residents of nursing homes and can lead to
      adverse effects such as a decrease in the activities of daily living and quality
      of life. Existing literature on the prevalence of pain among older residents of
      nursing homes was reviewed. Of the studies that were reviewed here, 27 met the
      criteria of this study, and these were selected for further analysis. These
      studies were published from 1990 to 2009. There was a slight increase in the
      number of studies on this topic from 2004 onwards. It was clear that older
      residents commonly suffer from pain and other serious problems related to pain.
      The prevalence of pain in these studies appeared to be related to the research
      methods and data sources used as well as to the time frame of pain detection.
      Therefore, the results of such prevalence studies should be interpreted
      cautiously. It was also reported that higher pain intensity led to greater
      limitations in the activities of daily living. Insufficient use of analgesics for
      treating residents with pain was often reported, particularly in residents with a
      low cognitive status. Health professionals should be aware of the serious issues
      related to pain among nursing home residents and the fundamental right to have
      pain assessed and treated to the greatest extent possible.

PMID- 21095597
TI  - Barriers to pain management among adolescents with cancer.
AB  - Patient-related barriers to reporting pain and using analgesics (e.g., fear of
      addiction) can detrimentally affect pain management for adolescents with cancer.
      However, adolescent barriers have not been systematically investigated;
      furthermore, no instrument exists to measure these barriers. The purposes of this
      study were to examine the psychometric properties of the newly developed
      Adolescent Barriers Questionnaire (ABQ) and to describe adolescent barriers to
      pain management. The study was guided by a barriers model which suggests that
      barriers (beliefs) influence coping (hesitation to report pain, use of
      analgesics, and adequacy of analgesics), which in turn affects outcomes (pain
      severity and quality of life). Sixty adolescent patients with cancer aged 12-17
      years completed the ABQ; 22 of which reported pain and also completed measures of
      hesitation, analgesic use, pain severity, and physical and psychosocial function.
      Initial testing provided evidence that the ABQ is reliable and valid. Internal
      consistency estimates for the total scale ranged from 0.91 to 0.94 and for the
      subscales ranged from 0.54 to 0.96. Test-retest reliability over a 2-week period
      was r=0.82. Construct validity was supported by a significant positive
      relationship between barriers scores and coping (hesitation to report pain and to
      use analgesics). However, coping did not mediate the relationship between
      barriers and outcomes. All of the adolescents reported some barriers. Barriers
      scores did not vary by age or gender. The leading barrier was concern that social
      activities would be restricted if pain was reported. Clearly, adolescents have
      barriers that can interfere with pain management. Interventions are needed to
      identify and help adolescents overcome these barriers.

PMID- 21095598
TI  - Best evidence of psychosocially focused nonpharmacologic therapies for symptom
      management in older adults with osteoarthritis.
AB  - Osteoarthritis (OA) is a common chronic joint problem among older adults which
      causes severe pain and loss of physical function. Early diagnosis and proper
      management are important strategies in delaying disease exacerbation and
      maintaining physical mobility. The number of older adults suffering from joint
      diseases is increasing, and many of these individuals are using nonpharmacologic
      therapies (NPTs) to control pain. Because there is no cure for OA, interventions
      have aimed at controlling pain, improving joint function, and minimizing
      disability. This paper reviewed literature that examines the effects of
      psychosocially focused NPTs, including education, self-management, coping skills,
      and social support for pain control and function improvement in older adults with
      OA. This review demonstrates that NPTs do not have the side effects that
      pharmacologic therapies do, but more high-quality clinical trials with
      appropriate design and meta-analyses need to be conducted to more clearly
      identify the effects of such NPTs to control pain and improve physical function
      in older adults with OA. Because many NPTs are easy to learn and use without
      serious side effects, nurses can play a pivotal role in helping patients
      implement NPTs for maximal benefit.

PMID- 21095599
TI  - Prior conditions influencing nurses' decisions to adopt evidence-based
      postoperative pain assessment practices.
AB  - Over the past 30 years, postoperative pain relief has been shown to be
      inadequate. To provide optimal postoperative pain relief, it is imperative for
      nurses to use evidence-based postoperative pain assessment practices. This
      correlational descriptive study was conducted to identify factors, termed prior
      conditions, that influenced nurses' decisions to adopt three evidence-based
      postoperative pain assessment practices. A convenience sample of nurses who cared
      for adult postoperative patients in two Midwestern hospitals were surveyed, and
      443 (46.9%) nurses responded. The previous practice and innovativeness of nurses
      were supportive of adoption of the three practices. Nurses felt that patients
      received adequate pain relief, which is unsupportive of adoption of the three
      practices because there is no impetus to change. Nurses who perceived the prior
      conditions as being supportive of adoption of pain management practices used
      multiple sources to identify solutions to clinical practice problems, and those
      who read professional nursing journals were more likely to have adopted the three
      practices and were more innovative. The number of sources used to identify
      solutions to clinical practice problems, previous practices, and innovativeness
      were predictive of nurses' adoption of the three evidence-based postoperative
      pain assessment practices. Nurses need to be encouraged to use multiple sources,
      including professional nursing journals, to identify solutions to clinical
      practice problems. Innovative nurses may be considered to be opinion leaders and
      need to be identified to promote the adoption of evidence-based postoperative
      pain assessment practices. Further exploration of the large unexplained variance
      in adoption of evidence-based postoperative pain assessment practices is needed.

PMID- 21095600
TI  - Pain in children with Down syndrome: assessment and intervention by parents.
AB  - The aims of this study were: 1) to describe how parents assess pain in their
      child with Down syndrome; and 2) to examine the relationship between pain
      assessment and decisions by parents to intervene to relieve pain in the child.
      Twelve parents of school-age children with Down syndrome (ages 6-12 years) were
      interviewed. Data analysis followed Spradley's Developmental Research Sequence
      (1979). This included domain analysis, taxonomic analysis, componential analysis,
      and theme development. Four themes emerged from the data analysis. Theme 1: Being
      sensitive to verbal and behavioral attributes of pain in the child. Parents
      reported that they assessed pain in their child with Down syndrome through the
      child's use of words to express pain, pointing or showing pain location, crying,
      changes in usual activities, and seeking closeness to the parent. Theme 2:
      Recognizing emotional and social responses to pain. Parents reported that
      emotional responses (e.g., anger, fear, frustration, acting out) were part of the
      pain expressions of their child with Down syndrome. Theme 3: Identifying
      differences in pain expressions between child and siblings. Parents used
      strategies to assess pain based on their beliefs that the child was less verbal,
      slower to complain, and less bothered by pain than siblings. Strategies included
      questioning the child to elicit self-reporting of pain and observing the child's
      behaviors. Theme 4: Making decisions to intervene. Parents reported that actions
      to relieve pain in their child with Down syndrome included more psychologic
      measures than physical measures, but otherwise no differences were noted in the
      actions taken for the child and the child's siblings.

PMID- 21095601
TI  - Nerves are living structures whose injury requires urgent repair.

PMID- 21095602
TI  - The war of the 'Noses'.

PMID- 21095603
TI  - [15 years AZQ (medical central office for quality in medicine)].

PMID- 21095604
TI  - [Transformation of an "aged" periodical over the last 15 years].

PMID- 21095605
TI  - [After seven years of National Disease Management Guidelines: quo vadis?].
AB  - After seven years the National Disease Management Guidelines Programme (German DM
      CPG Programme) that was established under the auspices of the German Medical
      Association, the National Association of Statutory Health Insurance Physicians
      and the Association of the Scientific Medical Societies in Germany has been
      widely accepted by both health care professionals and patients. DM-CPGs are
      available as tools for knowledge and quality management for widespread chronic
      diseases showing need for improvement in treatment pathways and coordination
      between health care providers. The main objective of the German DM-CPG Programme
      is to establish consensus among the medical professions on evidence-based key
      recommendations covering all sectors of health care provision and facilitating
      the coordination of care for the individual patient over time and across
      interfaces. German DM-CPGs provide a conceptual basis for disease management and
      integrative care aiming at the implementation of best practice recommendations
      for prevention, acute care, rehabilitation, chronic care and management aspects
      for high priority health care topics. Thus, representatives of all disciplines,
      professions and patients concerned with the topic of an individual German DM-CPG
      are involved in the development process. The methodology of guideline development
      is in accordance with international standards. However, the improvement of
      strategies for effective implementation and continuous update remain challenging.
      Future work will also focus on content-related aspects such as co-morbidity,
      gender and migration background.

PMID- 21095606
TI  - [Diversity in spite of standards: the special features of NDGMs].
AB  - For seven years the German National Disease Management Guidelines Programme (NDMG
      Programme) has been supported by its funding bodies: the German Medical
      Association, the National Association of Statutory Health Insurance Physicians,
      and the Association of Scientific Medical Societies. The objectives of the NDMG
      Programme are to develop and to implement comprehensive national clinical
      guidelines for the management of selected illnesses. Key points of NDMG
      methodology are the strict adherence to the principles of evidence-based medicine
      as well as the avoidance of contradictory recommendations by means of neutrally
      facilitated consensus rounds. Despite the standardised NDMG methodology each
      guideline has individual structural and content features that make it unique. For
      example, the complex illness type 2 diabetes is presented in topic- and problem
      oriented NDMG modules. For unipolar depression, the NDMG was simultaneously
      developed as a S3 guideline. Furthermore each NDMG group was faced with its own
      content-based challenges. For instance, in the case of the NDMG Low-back Pain the
      guideline group intensely and controversially discussed the definition of
      unspecific low-back pain. The NDMG Asthma does not solely address adults, but
      also children and adolescents, and the NDMG Heart Failure for the first time
      covers other health care relevant aspects such as multimorbidity and psychosocial
      factors in detail. The following article aims to deliver insight into the
      diversity of the development of National Disease Management Guidelines and to
      demonstrate the complexity of guideline development.

PMID- 21095607
TI  - [Gender: new methodological approaches in guideline development].
AB  - Gender and diversity have a strong impact on health and illness as evidenced by
      sex and gender differences in the onset and progression of diseases as well as in
      diagnosis, therapy, and therapeutic outcome. The number of sex/gender-specific
      studies in medicine has increased steadily in recent years, indicating sex
      (biological) and gender (social) differences in numerous diseases. Despite this
      evidence, however, sex/gender differences are rarely considered in medical
      practice or in health systems, suggesting a delay in transferring such research
      into evidence-based medical treatment. Similarly, quality improvement guidelines
      in medical care do not systematically integrate the sex/gender perspective.
      Against this backdrop, this paper seeks to enumerate the necessary components of
      a guideline development and evaluation process that systematically integrates
      sex/gender differences in addition to providing a sex/gender-based methodological
      approach. The latter is illustrated by a pilot study in which four international
      guidelines on depression were selected. The sex/gender appropriateness of these
      guidelines was analysed using two methods: first, sex/gender-relevant words were
      counted; and second, relevant sex/gender differences were summarised based on a
      systematic literature review and then compared with the information given in the
      guidelines. The findings of the pilot study revealed that although strong
      evidence exists on sex/gender differences in depression, such research was rarely
      implemented in the guidelines. Given the scope and potential of guidelines to
      improve the quality of health care, it is essential that they consider the
      crucial role of sex/gender differences. To date, sex/gender differences have been
      insufficiently addressed in guideline development and evaluation when they should
      be an integral component of the process.

PMID- 21095608
TI  - [Diagnostic imaging in oncology--evidence reviews for evidence based guidelines
      by the Agency of Quality for Medicine (AZQ)].
AB  - Within the context of the development of evidence-based oncology guidelines, the
      Agency for Quality in Medicine undertook evidence reviews for diagnostic imaging
      procedures. Systematic searches retrieved no randomised controlled trials, but
      only cohort studies and case series of mostly moderate quality. The identified
      studies provided only a restricted basis for the guideline recommendations as
      their validity was limited and only outcomes of diagnostic accuracy were
      examined. However, decision criteria for recommending diagnostic strategies
      significantly comprise judgements about required resources and availability of
      diagnostic imaging procedures. These criteria as well as patient out-comes were
      mostly implicit and should be explicated in future. In order to increase the
      relevance of evidence reviews for oncological diagnosis, high quality studies
      which examine resources and patient-centred outcomes for diagnostic strategies
      are required.

PMID- 21095609
TI  - [After 15 years of AZQ: 10 years of safety for patients].
AB  - The German Agency for Quality in Medicine (AZQ) has been actively addressing the
      topic patient safety for ten years. AZQ's work in the field has focused on
      establishing a patient safety expert circle, publishing various articles on the
      subject, developing a patient safety continuing education curriculum, setting up
      a patient safety internet forum, and participating in the WHO initiative "Action
      on Patient Safety: High 5s". Furthermore, "CIRSmedical.de", a reporting and
      learning system for German medical professionals supported and maintained by AZQ,
      developed into the nationwide "CIRSmedical.de Network". In the following article
      these activities and how they relate to other national and international patient
      safety programs are described.

PMID- 21095610
TI  - [Doctor rating sites: which of them find the best doctors in Germany?].
AB  - Online doctor rating sites have been increasingly discussed in the past few
      years, but scientific papers on the issue are rare. Results of a recent study
      could show that online doctor rating sites do not support patients in identifying
      qualified doctors. Against this background, the German Medical Association and
      the National Association of Statutory Health Insurance Physicians have
      commissioned the German Agency for Quality in Medicine (AZQ) with developing
      quality standards for online doctor rating sites. The list of quality criteria,
      published in December 2009, contains 40 questions and defines the following main
      quality standards: data privacy, transparency in terms of operators and funding,
      a clear and understandable assessment procedure, a strict separation of content
      and advertisement, measures against defamation, discrimination and deception. At
      present,all German online doctor rating sites are being assessed according to the
      list of quality criteria by AZQ. The results will be published.

PMID- 21095611
TI  - [Informed decisions: patient and consumer information at the German Agency for
      Quality in Medicine (AZQ)].
AB  - The concept of informed decision making does not only comply with the ideals of
      the self-determining citizen. In politics and society it is more and more
      understood as an individual obligation. In order to be capable of making
      competent decisions regarding treatment options, citizens have to be provided
      with high quality information. With the aim of facilitating patients' and
      consumers' orientation in health care questions, the German Agency for Quality in
      Medicine (AZQ) has been committed to developing and promoting the use of reliable
      patient information for more than ten years. AZQ's activities are based on four
      main principles: development of patient versions of high quality clinical
      practice guidelines; provision of patient information which has been assessed
      according to its formal quality; provision of information on the German health
      care system (checklists); further development of quality standards and methods.

PMID- 21095612
TI  - [The German Medical eLibrary].
AB  - The internet offers doctors plenty of high-value information for medical
      questions. However, several barriers impair the preoccupation with this
      information, most notably lack of time, far too much offered information and
      missing confidence in the reliability of the offers. The following article points
      out how the Agency for Quality in Medicine developed the Internet portal "German
      Medical eLibrary" (Arztbibliothek) in which information is transparently pre
      selected and grouped in a structured way as well as easy to find with the help of
      a simple, user-friendly search function. Evidence-based high-quality information
      is available in an easy, quick and well-directed manner. Thus the "German Medical
      eLibrary" facilitates knowledge management as a cornerstone of high-quality
      medical care.

PMID- 21095614
TI  - [Knowledge management in AZQ (medical central office for quality in medicine)].

PMID- 21095615
TI  - ["He who wants to build high towers must spend a lot of time on the foundation".
      On the development of the German Network of Evidence Based Medicine (interview by
      Sylvia Sanger)].

PMID- 21095616
TI  - [Acceptance of dental care guidelines by quality circles].
AB  - The discussion about the advantages of evidence-based guidelines in daily dental
      practice is a matter of current interest. In this report three high-quality S3
      level pilot guidelines which have been developed in dental medicine were
      evaluated under practice conditions. Quality circles in the city of Hamburg
      readily accepted to join this survey. By means of a questionnaire before and
      after a 4-month field test in dental practices the participants of quality
      circles were interviewed about their attitude towards guidelines and to the
      application of the guidelines. In addition, the experience gained with the
      application of the guidelines was incorporated into a group discussion with
      moderators of quality circles. The inclusion of quantitative and qualitative
      methods enabled a recording of the complete range of differentiated opinions
      concerning the application of guidelines. The results show that the concerns
      expressed by participants can be reduced by integrating guidelines in their
      everyday clinical practice. A strength and weakness analysis demonstrates that
      the quality circle moderators' attitudes towards approved guidelines range from
      rather positive to ambivalent. Field testing by quality circles proves to be a
      sound method for evaluating the acceptance of guidelines in daily practice.

PMID- 21095617
TI  - Resting heart rate is associated with blood pressure in male children and
      adolescents.
AB  - OBJECTIVES: To analyze the association between resting heart rate and blood
      pressure in male children and adolescents and to identify if this association is
      mediated by important confounders. STUDY DESIGN: Cross-sectional study carried
      out with 356 male children and adolescents from 8 to 18 years old. Resting heart
      rate was measured by a portable heart rate monitor according to recommendations
      and stratified into quartiles. Blood pressure was measured with an electronic
      device previously validated for pediatric populations. Body fatness was estimated
      by a dual-energy x-ray absorptiometry. RESULTS: Obese subjects had values of
      resting heart rate 7.8% higher than nonobese (P = .001). Hypertensive children
      and adolescents also had elevated values of resting heart rate (P = .001). When
      the sample was stratified in nonobese and obese, the higher quartile of resting
      heart rate was associated with hypertension in both groups of children and
      adolescents. CONCLUSIONS: This study confirms the existence of a relationship
      between elevated resting heart rate and increased blood pressure in a pediatric
      population, independent of adiposity, ethnicity and age.

PMID- 21095618
TI  - A kinematic analysis of visually-guided movement in Williams syndrome.
AB  - Previous studies have reported that people with the neurodevelopmental disorder
      Williams syndrome exhibit difficulties with visuomotor control. In the current
      study, we examined the extent to which visuomotor deficits were associated with
      movement planning or feedback-based on-line control. We used a variant of the
      Fitts' reciprocal aiming task on a computerized touchscreen in adults with WS, IQ
      matched individuals with Down syndrome (DS), and typically developing controls.
      By manipulating task difficulty both as a function of target size and amplitude,
      we were able to vary the requirements for accuracy to examine processes
      associated with dorsal visual stream and cerebellar functioning. Although a
      greater increase in movement time as a function of task difficulty was observed
      in the two clinical groups with WS and DS, greater magnitude in the late
      kinematic components of movement-specifically, time after peak velocity-was
      revealed in the WS group during increased demands for accuracy. In contrast, the
      DS group showed a greater speed-accuracy trade-off with significantly reduced and
      more variable endpoint accuracy, which may be associated with cerebellar
      deficits. In addition, the WS group spent more time stationary in the target when
      task-related features reflected a higher level of difficulty, suggestive of
      specific deficits in movement planning. Our results indicate that the visuomotor
      coordination deficits in WS may reflect known impairments of the dorsal stream,
      but may also indicate a role for the cerebellum in dynamic feed-forward motor
      control.

PMID- 21095619
TI  - Hepatitis C virus expressing flag-tagged envelope protein 2 has unaltered
      infectivity and density, is specifically neutralized by flag antibodies and can
      be purified by affinity chromatography.
AB  - Hepatitis C virus (HCV) purification by ultracentrifugation is difficult because
      of the low and heterogeneous density of native and cultured viruses. It was
      recently shown that inserting flag tag into envelope protein 2 (E2) of HCV
      permitted virus purification by affinity chromatography. However, flag-tagged
      viruses had drastically altered properties, and purification yield was low. In
      this study, we found that insertion of flag tag at the N-terminus of E2 in HCV
      recombinant J6/JFH1 did not affect viability in Huh7.5 cells, and that flag
      tagged virus had physiochemical properties similar to the original virus. Flag
      tagged virus was susceptible to flag-specific antibody neutralization, and
      infected cells could be immuno-stained by anti-flag antibodies. Using affinity
      chromatography with anti-flag resin we repeatedly obtained ~30% recovery of
      infectious particles. The full viability and unaltered physiochemical properties
      of flag-tagged HCV is an important improvement for utilizing these viruses for
      imaging, virion composition analysis and possibly vaccine development.

PMID- 21095620
TI  - Effects of G-CSF on systemic inflammation, coagulation and platelet activation in
      patients with acute myocardial infarction.
AB  - INTRODUCTION: In the prospective, randomised, double-blind, placebo-controlled
      Regenerate Vital Myocardium by Vigorous Activation of Bone Marrow Stem Cells
      (REVIVAL)-2 trial patients with acute myocardial infarction (AMI) and successful
      mechanical reperfusion received granulocyte-colony stimulating factor (G-CSF, 10
      MUg/kg KG s.c.) or placebo for 5 days. Aim of this substudy was to assess the
      impact of G-CSF on systemic inflammatory and procoagulant responses and platelet
      activation. METHODS AND RESULTS: Before and five days after G-CSF (n=56) or
      placebo (n=58) circulating cytokine concentrations of interleukin (IL)-1beta, IL
      6, IL-8, IL-10, IL-12 and Tumor-Necrosis Factor-alpha (TNF-alpha were measured.
      Prothrombin fragment F1+2 and Tissue Factor activity served as a measure for
      activated coagulation. Platelet activation was characterized by cell surface
      expression of the activated fibrinogen receptor (PAC-1), P-selectin and CD40L by
      flow cytometry. Administration of G-CSF was associated with elevated TNF-alpha
      and CRP concentrations compared to the placebo group after 5 days. Other
      cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12) were comparable after treatment
      with G-SCF or placebo. Similarly, circulating prothrombin fragments F1+2, TF
      activity and platelet activation did not differ in both groups. CONCLUSION:
      Treatment with G-CSF in patients with AMI was associated with enhanced
      proinflammatory TNF-alpha and CRP levels but no activation of coagulation.

PMID- 21095621
TI  - Vital exhaustion, depressive symptoms and serum triglyceride levels in high-risk
      middle-aged men.
AB  - The role of elevated serum triglyceride level as a risk factor of coronary artery
      disease is well established. Previous results have also indicated that depression
      or depressive symptoms and vital exhaustion correlate with triglyceride levels.
      The aim of this study was to investigate the associations of depressive symptoms,
      vital exhaustion, and health behavior with serum triglyceride levels. The study
      sample comprised 444 high-risk middle-aged men. Participants completed self
      report questionnaires before laboratory tests. Triglyceride concentrations were
      measured by the enzymatic method. Vital exhaustion and depression were associated
      with unhealthy lifestyles and triglycerides. Vital exhaustion and depression were
      closely correlated constructs with comparable relations with known coronary
      artery disease risk factors. When comparing vital exhaustion (VE) to Beck
      Depression Inventory (BDI), however, the first one had a stronger correlation
      with triglycerides (TG), and also, path analyses showed a direct link from vital
      exhaustion to body mass index but not from depression. Both vital exhaustion and
      depression are related to triglyceride levels. The relations are partly mediated
      by unfavorable lifestyles. Although vital exhaustion is not so commonly assessed
      as depression, results of this study support the importance of vital exhaustion
      as a health-related psychological risk factor.

PMID- 21095623
TI  - Abnormal coagulation and platelet profile in patients with obstructive sleep
      apnea syndrome.

PMID- 21095624
TI  - Unrecognized noncompaction on the internet.

PMID- 21095622
TI  - Protective factors for posttraumatic stress disorder symptoms in a prospective
      study of police officers.
AB  - Although police officers are frequently exposed to potentially traumatic
      incidents, only a minority will develop chronic posttraumatic stress disorder
      (PTSD). Identifying and understanding protective factors could inform the
      development of preventive interventions; however, few studies have examined this.
      In the present prospective study, 233 police officers were assessed during
      academy training and again following 2 years of police service. Caucasian race,
      less previous trauma exposure, and less critical incident exposure during police
      service as well as greater sense of self-worth, beliefs of greater benevolence of
      the world, greater social support and better social adjustment, all assessed
      during academy training, were associated with lower PTSD symptoms after 2 years
      of service. Positive personality attributes assessed during training with the NEO
      Five-Factor Personality Inventory were not associated with lower PTSD symptoms.
      In a hierarchical linear regression model, only Caucasian race, lower critical
      incident exposure during police service, greater assumptions of benevolence of
      the world and better social adjustment during training remained predictive of
      lower PTSD symptoms after 2 years of police service. These results suggest that
      positive world assumptions and better social functioning during training may
      protect police officers from critical incident related PTSD.

PMID- 21095625
TI  - Influence of AIN-93 diet on mortality and cardiac remodeling after myocardial
      infarction in rats.
AB  - BACKGROUND: The AIN-93 diet was proposed by the American Institute of Nutrition
      with the objective of standardising studies in experimental nutrition. Our
      objective was to analyze the effects of AIN-93 diet after myocardial infarction
      in rats. METHODS: Post weaning, the animals were divided into two groups: control
      (C, n=62), fed the standard diet of our laboratory (Labina); AIN-93 Group (n=70),
      fed the AIN-93 diet. Achieving 250 g, the animals were subjected to myocardial
      infarction. RESULTS: Early mortality was increased in AIN-93 animals, associated
      with lower serum levels of calcium, magnesium, potassium, sodium, and phosphorus.
      On the other hand, after 90 days, AIN-93 showed smaller normalized left
      ventricular dimensions. The caloric and carbohydrate intake was smaller, but the
      fat intake was higher in AIN-93 rats. AIN-93 group also showed increased levels
      of beta-hydroxyacylcoenzyme A dehydrogenase and citrate synthase. In addition,
      serum levels of insulin and cardiac levels of malondialdehyde, metalloproteinases
      2 and -9, and TNF-alpha and IFN-gamma were decreased in the AIN-93 group.
      CONCLUSION: AIN-93 diet increased early mortality, while attenuated the chronic
      remodeling process after experimental coronary occlusion. Therefore, this diet
      has biological effects and should be use with attention in this model.

PMID- 21095626
TI  - Renal outcome of contrast-induced nephropathy after coronary angiography in
      patients with chronic kidney disease.

PMID- 21095627
TI  - Incremental value and safety of oral ivabradine for heart rate reduction in
      computed tomography coronary angiography.
AB  - BACKGROUND: Heart rate (HR) reduction is essential to achieve optimal image
      quality and diagnostic accuracy with computed tomography coronary angiography
      (CTCA). Administration of ivabradine could be an attractive alternative to beta
      blockade to reduce HR. METHODS: One-hundred-twenty-three patients referred for
      CTCA were prospectively enrolled. Patients were divided in two groups depending
      on the absence or presence of chronic beta-blockade treatment. Within the two
      groups patients were randomized to either no additional premedication or oral
      ivabradine for 5 days prior to CTCA. In presence of chronic beta-blockade therapy
      it was shifted to atenolol 50mg twice a day for 5 days prior to CTCA. HR and
      blood pressure were assessed at admission (T0), immediately before CTCA (T1) and
      during CTCA (T2). The target HR was <65 bpm. RESULTS: Ivabradine significantly
      reduced HR during CTCA. Mean relative HR reduction was 15% for controls, 12% for
      chronic beta-blockade, 19% for ivabradine and 24% for both chronic beta-blockade
      and ivabradine at T2 (p for trend <0.001). The rate of patients who reached the
      target HR at T2 was 83% in controls, 71% with chronic beta-blockade, 97% with
      ivabradine and 97% with both (p for trend <0.05). The percentage of patients that
      needed additional IV beta-blockade at T1 decreased from 69% to 40% with
      ivabradine and 30% with both (p for trend <0.05). CONCLUSIONS: Ivabradine is safe
      and effective in increasing the rate of patients at target HR and in reducing the
      need for additional IV beta-blockade in patients referred for CTCA.

PMID- 21095628
TI  - Perioperative oral nutritional support in surgical hip fracture patients:
      suggestions for the prevention of pressure ulcers.

PMID- 21095629
TI  - Self-Rating of the Effects of Alcohol (SRE): Predictive utility and reliability
      across interview and self-report administrations.
AB  - The Self-Rating of the Effects of Alcohol (SRE) is a widely used and well
      established measure of the level of response to alcohol. Although the SRE has
      been successfully used in studies of alcoholism etiology, including genetics,
      studies to date have not compared the self-report and interview formats. The
      objectives of this study are to: (a) test the predictive utility of the subscales
      of the SRE in relation to alcohol problems; and (b) test the reliability of the
      SRE in interview versus self-report formats. A sample of college drinkers (n=446)
      completed the SRE in a self-report format along with the Alcohol Use Disorders
      Identification Test (AUDIT). A subset of participants (n=34) returned to the
      laboratory and completed the SRE in a face-to-face interview format. All
      subscales of the SRE were robust predictors of alcohol problems accounting for as
      much as 25% of the variance in AUDIT scores. In addition, scores obtained via
      self-report and interview-based SRE were highly correlated (r=.70 to .80).
      Results support the predictive utility of the SRE and provide initial evidence
      that the self-report and interview formats produce reliable results and may be
      combined and/or used interchangeably.

PMID- 21095630
TI  - Epidermal growth factor receptor expression modulates antitumor efficacy of
      vandetanib or cediranib combined with radiotherapy in human glioblastoma
      xenografts.
AB  - PURPOSE: The purpose of this study was to determine the ability of radiation
      therapy (RT) combined with the tyrosine kinase inhibitors (TKI) vandetanib
      (antiepidermal growth factor receptor [EGFR] plus antivascular endothelial growth
      factor receptor [anti-VEGFR]) and cediranib (anti-VEGFR) to inhibit glioblastoma
      multiforme (GBM) growth. A secondary aim was to investigate how this regimen is
      modulated by tumor EGFR expression. METHODS AND MATERIALS: Radiosensitivity was
      assessed by clonogenic cell survival assay. VEGF secretion was quantified by
      enzyme-linked immunosorbent assay. GBM (U87MG wild-type EGFR [wtEGFR] and U87MG
      EGFR-null) xenografts were treated with vandetanib, cediranib, and RT, alone or
      in combinations. Excised tumor sections were stained for proliferative and
      survival biomarkers. RESULTS: In vitro, U87MG wtEGFR and U87 EGFR-null cells had
      similar growth kinetics. Neither TKI affected clonogenic cell survival following
      RT. However, in vivo, exogenous overexpression of wtEGFR decreased tumor doubling
      time (T2x) in U87MG xenografts (2.70 vs. 4.41 days for U87MG wtEGFR vs. U87MG
      vector, respectively). In U87MG EGFR-null cells, TKI combined with radiation was
      no better than radiation therapy alone. In U87MG wtEGFR, RT in combination with
      vandetanib (but not with cediranib) significantly increased tumor T2x compared
      with RT alone (T2x, 10.4 days vs. 4.8 days; p < 0.001). In vivo, growth delay
      correlated with suppression of pAkt, survivin, and Ki67 expression in tumor
      samples. The presence of EGFR augmented RT-stimulated VEGF release; this effect
      was inhibited by vandetanib. CONCLUSIONS: EGFR expression promoted tumor growth
      in vivo but not in vitro, suggesting a microenvironmental effect. GBM xenografts
      expressing EGFR exhibited greater sensitivity to both cediranib and vandetanib
      than EGFR-null tumors. Hence EGFR status plays a major role in determining a
      tumor's in vivo response to radiation combined with TKI, supporting a
      "personalized" approach to GBM management.

PMID- 21095631
TI  - High-density spore production of Piriformospora indica, a plant growth-promoting
      endophyte, by optimization of nutritional and cultural parameters.
AB  - Piriformospora indica is an axenically cultivable root endophytic fungus which
      exerts plant growth promoting effects on its host plants. To enable commercial
      production of its spores, the medium composition and culture conditions have been
      optimized in a 14 L bioreactor such that they result in maximum biomass during
      growth phase and in maximum spore yield during subsequent sporulation phase.
      Maximum spore yields were obtained with modified Kaefer medium using a glucose
      deprivation strategy. An enhancement of 100% in overall biomass productivity
      (0.18 g L(-1) h(-1)) and reduction of about 70% in the time (60 h) required to
      achieve the maximum spore yield (9.25*10(7) spores/mL) was achieved in comparison
      to the original Kaefer medium. The high spore yield obtained in the present study
      seems to be economical for commercial production of P. indica.

PMID- 21095633
TI  - Adult attachment and reports of pain in experimentally-induced pain.
AB  - Attachment theory has been proposed as a framework for understanding the
      development of chronic pain, with evidence supporting the overrepresentation of
      insecure attachment styles in chronic pain populations and links between insecure
      attachment and factors known to impact one's ability to cope with pain. The
      present study sought to extend two earlier studies exploring the relationships
      between adult attachment and communication of an acute pain experience, in
      anticipation of providing insight into individual differences in vulnerability in
      development of chronic pain. It was hypothesised that: (a) fearful attachment
      would be associated with perceptions of the pain as less intense, and (b) anxious
      attachment would be associated with lower pain thresholds. A convenience sample
      of 82 healthy adults completed self-report measures of attachment, neuroticism,
      and negative affect prior to taking part in a coldpressor pain inducement task.
      Results demonstrated that fearful attachment was associated with lower levels of
      pain intensity throughout the coldpressor task. In addition, dismissing
      attachment was also associated with less intense pain, as well as increased
      coldpressor endurance (tolerance) in the presence of a known assessor. These
      associations were retained after controlling for measures of neuroticism,
      negative affect, age, and social desirability. The results of this study are
      consistent with the proposition that fearful and dismissing individuals tend to
      mask their underlying distress caused by the pain experience, potentially leading
      to difficulties coping with pain over time.

PMID- 21095634
TI  - Effectiveness of music interventions for women with high anxiety during coronary
      angiographic procedures: a randomized controlled.
AB  - The purpose was to investigate if women with high pre-procedural anxiety reported
      higher degree of relaxation and comfort if listening to music during coronary
      angiographic procedures. A prospective randomized controlled trial was used
      included 68 patients undergoing coronary angiography and/or PCI. The women were
      allocated to receive calming music and standard care or standard care only.
      Relaxation, environmental sound and discomfort associated with lying still were
      assessed. There was significantly more positive impression of the sound
      environment and less discomfort associated with lying still in women listening to
      music in comparison to women who received only standard care. No effect in
      relaxation was found.

PMID- 21095635
TI  - Treatment of gynaecomastia--the orthopaedic option.

PMID- 21095636
TI  - An image based vibration sensor for soft tissue modal analysis in a Digital Image
      Elasto Tomography (DIET) system.
AB  - Digital Image Elasto Tomography (DIET) is a non-invasive elastographic breast
      cancer screening technology, based on image-based measurement of surface
      vibrations induced on a breast by mechanical actuation. Knowledge of frequency
      response characteristics of a breast prior to imaging is critical to maximize the
      imaging signal and diagnostic capability of the system. A feasibility analysis
      for a non-invasive image based modal analysis system is presented that is able to
      robustly and rapidly identify resonant frequencies in soft tissue. Three images
      per oscillation cycle are enough to capture the behavior at a given frequency.
      Thus, a sweep over critical frequency ranges can be performed prior to imaging to
      determine critical imaging settings of the DIET system to optimize its tumor
      detection performance.

PMID- 21095632
TI  - Glycogen synthase kinase 3: a point of convergence for the host inflammatory
      response.
AB  - The phosphatidylinositol 3-kinase (PI3K) pathway has been shown to play a central
      role in regulating the host inflammatory response. Recent studies characterizing
      the downstream effector molecules within the PI3K pathway have identified that
      the serine/threonine kinase, glycogen synthase kinase 3 (GSK3), plays a pivotal
      role in regulating the production of pro- and anti-inflammatory cytokines. In
      innate immune cells, GSK3 inactivation augments anti-inflammatory cytokine
      production while concurrently suppressing the production of pro-inflammatory
      cytokines. The role of GSK3 in T cell biology has also been studied in detail and
      is involved in regulating multiple downstream signaling processes mediated by the
      T cell receptor (TCR), the co-stimulatory molecule CD28, and the IL-17 receptor.
      In vivo studies assessing the therapeutic properties of GSK3 inhibitors have
      shown that the inactivation of GSK3 can protect the host from immune-mediated
      pathology and death. This review will highlight the immunological importance GSK3
      plays within different signal transduction pathways of the immune system, the
      cellular mechanisms regulating the activity of GSK3, the role of GSK3 in innate
      and adaptive immune responses, and the in vivo use of GSK3 inhibitors to treat
      inflammatory mediated diseases in animals.

PMID- 21095637
TI  - In vivo measurement of the complex shear modulus of rat mammary tumors using
      shear wave imaging techniques.
AB  - This paper summarizes dynamic measurements of shear modulus constants acquired
      for spontaneously growing rat mammary tumors. Measurements are compared with
      histology to determine tumor types. We also report on 3D shear-wave velocity
      fields acquired from an inhomogeneous hydrogel phantom with known mechanical
      properties. Phantom measurements enable us to interpret the effects of tissue
      structure and geometry on viscoelastic parameter estimates, and demonstrate that
      reproducible measurements are possible in vivo. Viscoelastic properties describe
      the mechano-environment of cells undergoing malignant transformation and tumor
      growth.

PMID- 21095638
TI  - Motion estimation using the monogenic signal applied to ultrasound elastography.
AB  - This paper presents a phase-based method for estimating subpixel motion in
      medical ultrasound imaging. The main novelty is to propose a closed form
      expression for local motion estimation in space domain based on the model of the
      monogenic signal. First, the proposed method uses the properties of the monogenic
      signal in order to extract local orientation and phase data of ultrasound images.
      Second, using these image features, we show how the proposed method can
      analytically estimate the dense motion field between a pair of images. This way
      of estimating motion provides subpixel accuracy without interpolating the images.
      For this reason, we show that the proposed method has high computational
      efficiency. Results on simulated and experimental data show that this method
      provides a better Contrast to Noise Ratio than a classical block-matching method
      applied to images that are 25 times larger (in number of pixels).

PMID- 21095639
TI  - Feasibility of a transient elastography technique for in vitro arterial
      elasticity assessment.
AB  - The early detection of biomechanical modifications in the arterial wall could be
      used as a predictor factor for various diseases, for example hypertension or
      atherosclerosis. In this work a transient elastography technique is used for the
      in vitro evaluation of the arterial wall elasticity. The obtained Young modulus
      is compared with the one obtained by a more classical approach: pressure-diameter
      relationships. As a sample an arterial phantom made of PolyVinyl Alcohol (PVA)
      gel was used. Diameter variation due to pressure variation inside the phantom was
      recorded by means of ultrasound. Through both techniques similar Young modulus
      estimations are obtained showing in this way the feasibility of applying
      transient elastography for the arterial wall elasticity assessment.

PMID- 21095640
TI  - An ECG ambulatory system with mobile embedded architecture for ST-segment
      analysis.
AB  - A prototype of a ECG ambulatory system for long term monitoring of ST segment of
      3 leads, low power, portability and data storage in solid state memory cards has
      been developed. The solution presented is based in a mobile embedded architecture
      of a portable entertainment device used as a tool for storage and processing of
      bioelectric signals, and a mid-range RISC microcontroller, PIC 16F877, which
      performs the digitalization and transmission of ECG. The ECG amplifier stage is a
      low power, unipolar voltage and presents minimal distortion of the phase response
      of high pass filter in the ST segment. We developed an algorithm that manages
      access to files through an implementation for FAT32, and the ECG display on the
      device screen. The records are stored in TXT format for further processing. After
      the acquisition, the system implemented works as a standard USB mass storage
      device.

PMID- 21095641
TI  - Smart phone as a tool for measuring anticipatory postural adjustments in healthy
      subjects, a step toward more personalized healthcare.
AB  - We present a study on using a smart phone as a tool to evaluate anticipatory
      postural adjustments (APA) before the beginning of normal gait in healthy
      subjects. The results show a significantly lower amplitude of anticipatory
      postural adjustments in the mediolateral axis (ML) when subjects used the non
      dominant leg for the first step compared with the amplitude when using the
      dominant leg. The use of smart phones as a tool for measuring APA enables more
      personalized and active healthcare for the population without the necessity of
      their buying or carrying other devices.

PMID- 21095642
TI  - Motor function assessment using wearable inertial sensors.
AB  - We present an approach to wearable sensor-based assessment of motor function in
      individuals post stroke. We make use of one on-body inertial measurement unit
      (IMU) to automate the functional ability (FA) scoring of the Wolf Motor Function
      Test (WMFT). WMFT is an assessment instrument used to determine the functional
      motor capabilities of individuals post stroke. It is comprised of 17 tasks, 15 of
      which are rated according to performance time and quality of motion. We present
      signal processing and machine learning tools to estimate the WMFT FA scores of
      the 15 tasks using IMU data. We treat this as a classification problem in
      multidimensional feature space and use a supervised learning approach.

PMID- 21095643
TI  - Configurable portable/ambulatory instrument for the analysis of the coordination
      between respiration and swallowing.
AB  - Physiological studies of swallowing and the diagnosis and treatment of dysphagia
      are crucially dependent of detailed information of respiratory and feeding
      events. Home telemonitoring is of great interest in this area, where large
      numbers of people have long term conditions. The purpose of this study was
      twofold: (1) describe a new configurable instrument that can be used in
      ambulatory and telemedicine applications and (2) evaluate the performance of this
      device in the description of physiological and abnormal events during water
      swallowing. The instrument is able to detect when water is beginning to enter the
      mouth of the volunteer, to unobtrusively monitor the respiration, and to
      characterize the elevation of the larynx. The performance of the system was
      tested in normal subjects and patients with dysphagia, showing results in close
      agreement with the physiology. We concluded that the developed system could be a
      useful tool for the ambulatory evaluation of respiratory and feeding events and
      for the implementation of telemedicine services, contributing to reduce the costs
      of the assistance offered to patients with dysphagia.

PMID- 21095644
TI  - Evaluation of a CE approved ambulatory patient monitoring device in a general
      medical ward.
AB  - An evaluation of a newly CE approved bedside monitoring device used in a general
      hospital ward is presented. This evaluation has shown that it is feasible to use
      the system within this environment to provide medical staff with supplementary
      information on patient health, at more frequent intervals than traditional
      monitoring methods. The physiological data recorded by the body worn device is
      wirelessly transmitted to a patient management system for storage and display.
      Good correlation between heart rate values recorded by hospital staff and those
      recorded by the automated Vitalsens VS100 system was observed. The system has
      highlighted clinical information that routine observations alone did not readily
      identify. This can provide clinicians with a better view of the overall health
      status of the patient. Such medical issues include those witnessed in this study,
      namely paroxysmal AF, ectopic beats, increasing heart rates recorded prior to a
      hypoglycaemic event, general high and low heart rate trends and various instances
      where clinically relevant ECG data has been captured.

PMID- 21095645
TI  - An EMG-based system for continuous monitoring of clinical efficacy of Parkinson's
      disease treatments.
AB  - Current methods for assessing the efficacy of treatments for Parkinson's disease
      (PD) rely on physician rated scores. These methods pose three major shortcomings:
      1) the subjectivity of the assessments, 2) the lack of precision on the rating
      scale (6 discrete levels), and 3) the inability to assess symptoms except under
      very specific conditions and/or for very specific tasks. To address these
      shortcomings, a portable system was developed to continuously monitor
      Parkinsonian symptoms with quantitative measures based on electrical signals from
      muscle activity (EMG). Here, we present the system design and the implementation
      of methods for system validation. This system was designed to provide continuous
      measures of tremor, rigidity, and bradykinesia which are related to the
      neurophysiological source without the need for multiple bulky experimental
      apparatuses, thus allowing more precise, quantitative indicators of the symptoms
      which can be measured during practical daily living tasks. This measurement
      system has the potential to improve the diagnosis of PD as well as the evaluation
      of PD treatments, which is an important step in the path to improving PD
      treatments.

PMID- 21095646
TI  - Detecting nonlinear causal interactions between dynamical systems by non-uniform
      embedding of multiple time series.
AB  - This study introduces a new approach for the detection of nonlinear Granger
      causality between dynamical systems. The approach is based on embedding the
      multivariate (MV) time series measured from the systems X and Y by means of a
      sequential, non-uniform procedure, and on using the corrected conditional entropy
      (CCE) as unpredictability measure. The causal coupling from X to Y is quantified
      as the relative decrease of CCE measured after allowing the series of X to enter
      the embedding procedure for the description of Y. The ability of the approach to
      quantify nonlinear causality is assessed on MV time series measured from
      simulated dynamical systems with unidirectional coupling (the Rossler-Lorenz
      deterministic system) and bidirectional coupling (two coupled stochastic
      systems). The method is then applied to real magnetoencephalographic data
      measured during a visuo-tactile cognitive experiment, showing values of causal
      coupling consistent with the hypothesis of a cross-processing of different
      sensory modalities.

PMID- 21095647
TI  - Methodology for multifractal analysis of heart rate variability: from LF/HF ratio
      to wavelet leaders.
AB  - The present contribution aims at proposing a comprehensive and tutorial
      introduction to the practical use of wavelet Leader based multifractal analysis
      to study heart rate variability. First, the theoretical background is recalled.
      Second, practical issues and pitfalls related to the selection of the scaling
      range or statistical orders, minimal regularity, parabolic approximation of
      spectrum and parameter estimation, are discussed. Third, multifractal analysis is
      connected explicitly to other standard characterizations of heart rate
      variability: (mono)fractal analysis, Hurst exponent, spectral analysis and the
      HF/LF ratio. This review is illustrated on real per partum fetal ECG data,
      collected at an academic French public hospital, for both healthy fetuses and
      fetuses suffering from acidosis.

PMID- 21095648
TI  - Wavelet leader based multifractal analysis of heart rate variability during
      myocardial ischaemia.
AB  - Heart rate variability is a non invasive and indirect measure of the autonomic
      control of the heart. Therefore, alterations to this control system caused by
      myocardial ischaemia are reflected in changes in the complex and irregular
      fluctuations of this signal. Multifractal analysis is a well suited tool for the
      analysis of this kind of fluctuations, since it gives a description of the
      singular behavior of a signal. Recently, a new approach for multifractal analysis
      was proposed, the wavelet leader based multifractal formalism, which shows
      remarkable improvements over previous methods. In order to characterize and
      detect ischaemic episodes, in this work we propose to perform a short-time
      windowed wavelet leader based multifractal analysis. Our results suggest that
      this new method provides appropriate indexes that could be used as a tool for the
      detection of myocardial ischaemia.

PMID- 21095649
TI  - Real-time feedback of dynamic cardiac repolarization properties.
AB  - Arrhythmia is a major health problem and is the subject of much research and
      computational modeling. The impact of this research has been limited by the
      availability of human data and by difficulties in its translation to clinical
      practice. This paper describes an expert system for analysis of cardiac
      electrogram signals, detecting local activation and repolarization times using
      heuristic algorithms that incorporate automatic rejection of measurements that
      are deemed to be unreliable. The fully-automated system operates in real-time to
      provide feedback to cardiologists of derived dynamic repolarization models, which
      could dramatically enhance research capabilities and produce novel diagnostic
      techniques and therapies.

PMID- 21095650
TI  - Medical software management: a failure analysis approach for maintenance and
      safety plan.
AB  - Medical software management represents one of the biggest future challenge in
      healthcare. Technology level is actually waiting for appropriate normative and
      regulatory support by including maintenance, assistance and safety. This paper
      aims to highlight the critical aspects in medical software management and
      specifically to provide a methodology in order to support decision makers
      responsible for medical software assistance in health structures. The results
      show how medical software effectiveness depends on technical, organizational and
      clinical aspects.

PMID- 21095651
TI  - Freespace estimation in an autonomous wheelchair using a stereoscopic camera
      system.
AB  - This paper is concerned with the estimation of the height and width of freespace
      based on a Bayesian Recursive (BR) algorithm for an autonomous wheelchair using a
      stereoscopic camera system for disabled people. A 2D distance map for the purpose
      of freespace estimation is converted from a 3D point map using geometric
      projection and computation. The comparison of this 2D map to a 2D map obtained
      from Laser is carried out. Moreover, freespaces in the 2D map are estimated using
      a BR algorithm based on uncertainty information and control data. Given the
      average probability, a possible movement decision is then made for the mobile
      wheelchair. Experimental results obtained in an indoor environment prove the
      effectiveness of this estimation algorithm.

PMID- 21095652
TI  - Voluntary motion support control of Robot Suit HAL triggered by bioelectrical
      signal for hemiplegia.
AB  - Our goal is to enhance the quality of life of patients with hemiplegia by means
      of an active motion support system that assists the impaired motion such as to
      make it as close as possible to the motion of an able bodied person. We have
      developed the Robot Suit HAL (Hybrid Assistive Limb) to actively support and
      enhance the human motor functions. The purpose of the research presented in this
      paper is to propose the required control method to support voluntarily motion
      using a trigger based on patient's bioelectrical signal. Clinical trials were
      conducted in order to investigate the effectiveness of the proposed control
      method. The first stage of the trials, described in this paper, involved the
      participation of one hemiplegic patient who is not able to bend his right knee.
      As a result, the motion support provided by the HAL moved the paralyzed knee
      joint according to his intention and improved the range of the subject's knee
      flexion. The first evaluation of the control method with one subject showed
      promising results for future trials to explore the effectiveness for a wide range
      of types of hemiplegia.

PMID- 21095653
TI  - Cable-driven elastic parallel humanoid head with face tracking for Autism
      Spectrum Disorder interventions.
AB  - This paper presents the development of new prismatic actuation approach and its
      application in human-safe humanoid head design. To reduce actuator output
      impedance and mitigate unexpected external shock, the prismatic actuation method
      uses cables to drive a piston with preloaded spring. By leveraging the advantages
      of parallel manipulator and cable-driven mechanism, the developed neck has a
      parallel manipulator embodiment with two cable-driven limbs embedded with
      preloaded springs and one passive limb. The eye mechanism is adapted for low-cost
      webcam with succinct "ball-in-socket" structure. Based on human head anatomy and
      biomimetics, the neck has 3 degree of freedom (DOF) motion: pan, tilt and one
      decoupled roll while each eye has independent pan and synchronous tilt motion (3
      DOF eyes). A Kalman filter based face tracking algorithm is implemented to
      interact with the human. This neck and eye structure is translatable to other
      human-safe humanoid robots. The robot's appearance reflects a non-threatening
      image of a penguin, which can be translated into a possible therapeutic
      intervention for children with Autism Spectrum Disorders.

PMID- 21095655
TI  - Using 'stall detection' as an auxiliary mechanism for sensing obstacles and hand
      grasping in arm prosthesis.
AB  - This paper proposes a novel method for sensing obstacles and hand grasping
      activities in electromechanical arm prosthesis. The described method is based on
      indirectly sensing 'Stall' condition in prosthesis actuators through hall-effect
      sensors already embedded on its dc motors, thus not requiring external sensors.
      To test the proposed methodology, an electromechanical arm prosthesis of 3
      degrees of freedom (DOF), plus 'open-close' of hand, which is being developed at
      CINVESTAV Mexico, was used. At the end of this paper, experimental measurements
      performed on the tested prosthesis, using and non using 'Stall Detection', are
      shown. We demonstrated that methodology can be used successfully for "sensing
      obstacles", but it cannot be used alone for "hand grasping". In any case, this
      technique demonstrated to be a good method to simplify and strengthen control of
      prosthesis.

PMID- 21095654
TI  - Autonomous assistance navigation for robotic wheelchairs in confined spaces.
AB  - In this work, a visual interface for the assistance of a robotic wheelchair's
      navigation is presented. The visual interface is developed for the navigation in
      confined spaces such as narrows corridors or corridor-ends. The interface
      performs two navigation modus: non-autonomous and autonomous. The non-autonomous
      driving of the robotic wheelchair is made by means of a hand-joystick. The
      joystick directs the motion of the vehicle within the environment. The autonomous
      driving is performed when the user of the wheelchair has to turn (90, 90 or 180
      degrees) within the environment. The turning strategy is performed by a
      maneuverability algorithm compatible with the kinematics of the wheelchair and by
      the SLAM (Simultaneous Localization and Mapping) algorithm. The SLAM algorithm
      provides the interface with the information concerning the environment
      disposition and the pose -position and orientation-of the wheelchair within the
      environment. Experimental and statistical results of the interface are also shown
      in this work.

PMID- 21095656
TI  - Stumble detection and classification for an intelligent transfemoral prosthesis.
AB  - This paper describes an approach for the real-time detection of stumble for use
      in an intelligent lower limb prosthesis, using accelerometers mounted on the
      prosthesis, and also describes an algorithm that classifies the stumble response
      as either an elevating or lowering type response. In order to validate the
      proposed approach, the investigators collected stumble data on 10 healthy
      subjects using accelerometers affixed to the subjects in a manner consistent with
      similar instrumentation on a transfemoral prosthesis. The proposed algorithms
      were shown to correctly identify stumbling and correctly classify the stumble
      response for all 19 stumbles and 34 control strides collected in the experiments.

PMID- 21095657
TI  - Biomechanical conceptual design of a passive transfemoral prosthesis.
AB  - In this study, we present the conceptual design of a fully-passive transfemoral
      prosthesis. The proposed design is inspired by the analysis of the musculo
      skeletal activity of the healthy human leg. In order to realize an energy
      efficient device, we introduce three storage elements, which are responsible of
      the energetic coupling between the knee and the ankle joints. Simulation results
      show that the power storage of the designed conceptual prosthesis is comparable
      with the human gait.

PMID- 21095658
TI  - A biomechanical model for the development of myoelectric hand prosthesis control
      systems.
AB  - Advanced myoelectric hand prostheses aim to reproduce as much of the human hand's
      functionality as possible. Development of the control system of such a prosthesis
      is strongly connected to its mechanical design; the control system requires
      accurate information on the prosthesis' structure and the surrounding
      environment, which can make development difficult without a finalized mechanical
      prototype. This paper presents a new framework for the development of
      electromyographic hand control systems, consisting of a prosthesis model based on
      the biomechanical structure of the human hand. The model's dynamic structure uses
      an ellipsoidal representation of the phalanges. Other features include
      underactuation in the fingers and thumb modeled with bond graphs, and a
      viscoelastic contact model. The model's functions are demonstrated by the
      execution of lateral and tripod grasps, and evaluated with regard to joint
      dynamics and applied forces. Finally, future work is suggested with which this
      model can be used in mechanical design and patient training as well.

PMID- 21095659
TI  - An empirical model of end-tidal CO(2) response to minute ventilation.
AB  - This paper presents an empirical model of end-tidal CO(2) (P(ET)CO(2)) response
      to minute ventilation (MV) for use in the closed-loop control of artificial
      respiration. An affine model structure consisting of a linear dynamic system
      followed by an affine transform is presented. It is proposed that this derives a
      low-order, high-fidelity representation of the respiratory process that can
      describe the positive and inversely proportional relationship between P(ET)CO(2)
      and MV. The efficacy of the model is evaluated using experimental respiratory
      data from 18 human subjects. The model performed well with a root-mean-squared
      error (RMSE) of 0.22+/-0.15mmHg and a coefficient of determination (r(2)) of
      0.81+/-0.18 (mean+/-SD) when a 2(nd)-order rational transfer function was used as
      the linear component of the model. The physiologic implication of the model is
      analyzed by comparison with a traditional compartment model that is widely used
      in pharmacological modeling.

PMID- 21095660
TI  - Basic study of brain injury mechanism.
AB  - The purpose of this study is to discuss the mechanism of brain injury
      experimentally paying attention to the pressure changes on the surface of a brain
      agar phantom generated by a cavitation.

PMID- 21095661
TI  - Thermal injury models for optical treatment of biological tissues: a comparative
      study.
AB  - The interaction of optical radiation with biological tissues causes an increase
      in the temperature that, depending on its magnitude, can provoke a thermal injury
      process in the tissue. The establishment of laser irradiation pathological limits
      constitutes an essential task, as long as it enables to fix and delimit a range
      of parameters that ensure a safe treatment in laser therapies. These limits can
      be appropriately described by kinetic models of the damage processes. In this
      work, we present and compare several models for the study of thermal injury in
      biological tissues under optical illumination, particularly the Arrhenius thermal
      damage model and the thermal dosimetry model based on CEM (Cumulative Equivalent
      Minutes) 43 degrees C. The basic concepts that link the temperature and
      exposition time with the tissue injury or cellular death are presented, and it
      will be shown that they enable to establish predictive models for the thermal
      damage in laser therapies. The results obtained by both models will be compared
      and discussed, highlighting the main advantages of each one and proposing the
      most adequate one for optical treatment of biological tissues.

PMID- 21095662
TI  - Application of Tikhonov and MTSVD methods to unfold experimental X-ray spectra in
      the radiodiagnostic energy range.
AB  - A thorough knowledge of the primary spectrum is very important for Quality
      Control (QC) of X-ray tubes. A methodology to assess primary spectrum using a
      Compton spectrometer has been simulated with the MCNP5 code based on the Monte
      Carlo (MC) method. The Pulse Height Distribution (PHD) recorded in the detector
      is related with the primary X-ray spectrum by means of a Response matrix.
      Tikhonov and Modified Truncated Singular Values Decomposition (MTSVD) unfolding
      methods have been applied to the Response matrix to assess the primary spectrum.
      Both methods are tested comparing unfolded results with theoretical spectra from
      IPEM-78 catalogue.

PMID- 21095663
TI  - Towards improved sedation control in critically ill patients.
AB  - Patients in intensive care units are often prescribed a combination of sedative
      and analgesic to manage anxiety and pain relief. Proper sedation management is
      crucial to patient recovery but few intensive care units routinely employ
      strategies that tailor drug delivery to ongoing patient needs. The Infuse-Rite
      has been developed to automate a protocol that eliminates the possibility of
      excessive sedation. Changing clinical demands have provided the impetus for
      ongoing enhancements to improve the sedation control of patients in intensive
      care.

PMID- 21095664
TI  - Miniaturized antennas for link between binaural hearing aids.
AB  - We have investigated the possibility of using the 2.45 GHz ISM band for
      communication between binaural hearing aids. The small size of a modern hearing
      aid makes it necessary to miniaturize the antennas to make this feasible. Two
      different types of hearing aid placements have been investigated: in the outer
      ear and in the ear canal. Both put strict demands on the size of the antenna,
      which have been miniaturized by applying disc loads and high permittivity
      materials. The investigations have been done by FDTD simulation of a modified SAM
      phantom head, where we have included a simple model of the ear canal. Simulations
      show that the outer ear placement is better, as it gives a total link loss of 48
      dB. The placement in the ear canal gives a total link loss of 92 dB.

PMID- 21095665
TI  - Wireless power delivery for wearable sensors and implants in Body Sensor
      Networks.
AB  - A recent study on witricity (wireless electricity) has demonstrated that wireless
      energy can be delivered over a moderate distance using strongly coupled magnetic
      resonance. The objective of this work is to apply the witricity technology to the
      problem of powering a wireless Body Sensor Network (wBSN). The theory of
      witricity is investigated using coupled mode theory. Compact witricity resonators
      are designed, and a working prototype of witricity powered wBSN is built and
      evaluated. An energy transfer efficiency of about 80 % over a distance of 15 cm
      is achieved. Besides the high efficiency, it has been observed that a certain
      misalignment between the transmitter and receiver has little effect on the power
      transfer. Our experimental results indicate that witricity provides a powerful
      solution to the energy supply problem of wBSN.

PMID- 21095666
TI  - Utilizing electromagnetic shielding textiles in wireless body area networks.
AB  - For privacy and radio propagation controls, electromagnetic shielding textile
      could be adopted in WBANs. The effect of including a commercially available
      electromagnetic shielding apron in WBANs was examined in this paper. By having
      both the coordinator and the sensor covered by the shielding apron, signal could
      be confined around the body; however signal strength can be greatly influenced by
      body movements. Placing the shielding apron underneath both antennas, the
      transmission coefficient could be on average enhanced by at least 10dB, with less
      variation comparing to the case when apron does not exist. Shielding textiles
      could be utilized in designing a smart suit to enhance WBANs performance, and to
      prevent signals travelling beyond its intended area.

PMID- 21095667
TI  - Wireless powered electronic sensors for biological applications.
AB  - Radio frequency identification technology is used to power a novel platform of
      sensor devices. The employed energy harvesting system of the individual sensors
      enables a blanking of the radio frequency field for a defined period, while
      supplying the sensor electronics with a highly stable voltage. This guarantees
      interference free operation of the electronic circuitry during measurements. The
      implementation of this principle is demonstrated for a sensor system which is
      based on insets for state-of-the-art micro-titer-plates. Each inset is carrying
      electronic circuitry and an interdigitated electrode system which is acting as
      sensor for recording alterations of the cell metabolism. The presented sensor
      devices work without batteries and are designed for impedance measurements on
      microbiological cell cultures under physiological relevant conditions.

PMID- 21095668
TI  - Low power wireless acquisition module for wearable health monitoring systems.
AB  - This paper presents a low power wireless acquisition module for use within
      wearable health monitoring systems and Ambient Assisted Living applications. The
      acquisition module provides continuous monitoring of the user's electrocardiogram
      (ECG) and activity, as well as the local temperature at the module. The module is
      placed on the chest of the user, and its wearability is achieved due to its
      fabrication based on a flexible PCB, and by the complete absence of connecting
      wires, as a result of the integration of flexible and dry ECG monitoring
      electrodes on the acquisition module, which do not require preparation with
      electrolyte gel. The design of the acquisition module also aimed for the
      minimization of power consumption to enable long-term continuous monitoring,
      namely concerning the wireless link, for which a proprietary low power solution
      was adopted. A low power analog frontend was custom designed for single-lead ECG
      monitoring, achieving a current consumption of 220 epsilonA. The wireless
      acquisition module has a current consumption down to 1.3 mA while processing the
      acquisition of sensor data, and 4 mA when the wireless transceiver is active.

PMID- 21095669
TI  - Time reversal microwave breast imaging for contrast-enhanced tumor
      classification.
AB  - This paper studies the decomposition of the time reversal operator (DORT, by the
      French acronym) technique for microwave breast lesion classification. We apply
      the finitedifference time-domain (FDTD) method to a realistic numerical breast
      phantom where lesion-like targets are artificially introduced, and obtain the
      multistatic data matrix (MDM) for a particular antenna array configuration. Then,
      the singular value decomposition (SVD) of this matrix is derived for different
      targets, which represent malignant and benign lesions. We show that the singular
      value spectrum can assist in classifying these targets as malignant or benign,
      especially in the case where contrast-enhanced agents can be employed to allow
      the analysis of differential backscatter data.

PMID- 21095670
TI  - A Biomechanical model of spiculated tumours under mammographic compressions.
AB  - The aim of this paper is to introduce effects well known to clinicians -but
      neglected to date- in the biomechanical modelling of breast malignant tumours. We
      develop a model of an isolated stellate breast tumour under mammographic
      compression forces. We study a range of reported mechanical properties, both
      linear elastic and hyperelastic. We also introduce different volumes of increased
      density/stiffness around the tumour. We show that each of these issues has a non
      negligible effect on stresses and strains/deformations.

PMID- 21095671
TI  - Effects of needle placement inaccuracies in hepatic radiofrequency tumor
      ablation.
AB  - The correct needle placement is one of the crucial tasks in performing
      radiofrequency tumor ablation (RFA). In this work we evaluated the effects of
      imperfect needle placement for RFAs that are performed with an expandable needle
      array by using a finite-element simulation. We performed simulations for normal
      liver tissue with hypo- and hyperperfused metastasis as well as for cirrhotic
      liver tissue with hepatocellular carcinoma (HCC). We found that the shortest
      distance from tumor to the border of the ablated region is significantly smaller
      even for just 5mm deviation from the position recommended by the generator
      manufacturer. In case of hyperperfused metastasis even the tumor itself might
      stay unablated which means a very high probability of local tumor recurrence.
      These results provide valuable information on acceptability of inaccurate needle
      position to the radiologist performing RFA.

PMID- 21095672
TI  - Real-time sleep quality assessment using single-lead ECG and multi-stage SVM
      classifier.
AB  - Sleep efficiency measures provide an objective assessment to gauge the quality of
      individual's sleep. In this study we present a home-based, automated and non
      intrusive system that is based on Electrocardiogram (ECG) measurements and uses a
      multi-stage Support Vector Machines (SVM) classifier to measure three indices for
      sleep quality assessment per 30 s epoch segment: Sleep Efficiency Index, Delta
      Sleep Efficiency Index and Sleep Onset Latency. This method provides an
      alternative to the intrusive and expensive Polysomnography (PSG) and scoring by
      Rechtschaffen and Kales visual method.

PMID- 21095673
TI  - A portable self-sensing rheometer for investigation and therapy of swallowing
      disorders.
AB  - Dysphagia is a medical condition in which the safety or efficiency of eating and
      drinking is compromised. Thin, watery fluids flow too quickly through the oral
      anatomy during an abnormal swallow, pre-empting airway protective mechanisms, and
      potentially resulting in fluid entry into the lung. Dysphagia therapy consists of
      reducing flow speed during swallowing by increasing fluid viscosity using
      thickeners. Bolus viscosity must be specified and presented to the patient within
      a well-defined range for effective therapy. Thickeners produce non-Newtonian
      fluids, rendering current subjective methods for fluid assessment unreliable.
      Widespread quantification of fluid viscosity is presently impractical as
      rheometers are costly and complicated to use. Alternative techniques also have
      disadvantages such as operation at shear rates inappropriate to fluid use. A
      simple and inexpensive rheometer has been constructed to remedy this situation
      using a self-sensing electromagnetic actuator. This avoids the need for separate
      force and displacement sensors, with benefits for simplicity and robustness. The
      actuator and fluid interface were designed for viscosities consistent with those
      used for dysphagia therapy. The self-sensing rheometer was found to be able to
      resolve the different dynamic viscosities obtained from three commonly used
      therapeutic fluid consistency levels in close agreement with results from a
      reference laboratory rheometer. Widespread use of the rheometer could remove the
      subjectivity of fluid assessment, increasing accuracy of fluid specification and
      therapy across all consistencies and fluid types.

PMID- 21095674
TI  - Electronic temperature monitoring during the decompression surgery of the facial
      nerve.
AB  - Despite of its apparent protection by being located deep in a bony canal, the
      facial nerve is a cranial pair of nerves more vulnerable to traumatic injuries.
      The surgical accidents are the most frequent causes of intratemporal
      complications of the facial nerve. Among the postoperative sequelae, the thermal
      injuries are common due to overheating of the otologic burr resulting in facial
      paralysis. For the prevention of thermal injuries in the facial nerve was
      designed a data acquisition board to obtain the temperature measured by
      thermocouples using a PC and parallel communication. The signals from the
      temperature sensors passed through conditioning for amplification and analog to
      digital data conversion. Afterwards, they were stored on a computer for the
      statistical analysis and the visualization of the curves of variation of the
      measured temperatures. These curves provide the verification of the facial nerve
      temperature ascending and descending time during surgery steps to access the
      nerve. These data provide a substantial safe working margin to the surgeon.

PMID- 21095675
TI  - Intraoperative multichannel audio-visual information recording and automatic
      surgical phase and incident detection.
AB  - Identification, analysis, and treatment of potential risk in surgical workflow
      are the key to decrease medical errors in operating room. For the automatic
      analysis of recorded surgical information, this study reports multichannel audio
      visual recording system, and its review and analysis system. Motion in operating
      room is quantified using video file size without motion tracking. Conversation
      among surgical staff is quantified using fast Fourier transformation and
      frequency filter without speech recognition. The results suggested the
      progression phase of surgical procedure.

PMID- 21095676
TI  - PhysioDoloris: a monitoring device for analgesia / nociception balance evaluation
      using heart rate variability analysis.
AB  - Continuous Analgesia / Nociception balance evaluation during general anesthesia
      could be of precious help for the optimization of analgesic drugs delivery,
      limiting the risk of toxicity due to the use of opioid drugs, limiting the risk
      of post operative hyper algesia, and, probably, reducing time of recovery after
      surgical procedure. Heart Rate Variability analysis has been shown in several
      studies to measure the Autonomic Nervous System tone, which is strongly
      influenced by anesthetic drugs. Recording RR series during general anesthesia
      enabled us to observe that the Respiratory Sinus Arrhythmia pattern changed when
      a surgical stimulation was painful, even though the patient was not conscious. We
      have previously developed and evaluated a pain / analgesia measurement algorithm
      based on the magnitude analysis of the respiratory patterns on the RR series. In
      this paper, we present the development of a monitoring device (PhysioDoloris),
      based on the previously described technology, giving in real time an Analgesia
      Nociception Index (ANI) which can be used during general anesthesia in order to
      give to the anesthetist, a complementary tool for optimized drug delivery.

PMID- 21095677
TI  - Determining levels of arousal using electrocardiography: a study of HRV during
      transcranial magnetic stimulation.
AB  - Introduction. Electrocardiography (ECG) can be used to collect heart rate data
      which in turn can be used to measure heart rate variability (HRV). The
      sympathetic and parasympathetic nervous systems have the ability to affect this
      variability, which can ultimately affect arousal levels.

PMID- 21095678
TI  - Technological platform for biomechanical analysis of static and dynamic tests of
      upper and lower limbs.
AB  - One of the most important elements for the rehabilitation process regards to the
      correct evaluation of the biomechanical and the electrophysiological responses.
      This evaluation must be done during the therapy. In general, the improvements
      achieved by the treatment are slightly and difficult to be distinguished. This is
      a difficult task when the changes in the signals obtained by the bio-amplifiers
      (EMG, electro-goniometry, etc) are evaluated by a wired system because the
      patient cannot interact with its environment freely. The present work tackles the
      design, construction and implementation of a platform to carry out biomechanical
      analysis for upper and lower limbs. The included variables in the biomechanical
      system are the angular position, linear acceleration, electromyography signals
      and force executed by the limbs. The designed scheme considers the wireless
      monitoring of relevant signals; such variables allow us to analyze the
      effectiveness achieved by the therapy. Processing and data exhibition are carry
      out in a personal computer. Two application examples regarding the biomechanical
      wrist evaluation and the EMG correlation are presented. Nonlinear algorithms to
      analyze the information obtained in the system are used to evaluate the
      biomechanical responses produced in different patients.

PMID- 21095680
TI  - Integrating optical fiber force sensors into microforceps for ORL microsurgery.
AB  - The delicate anatomy of the ear require surgeons to use great care when operating
      on its internal structures. One example for such an intervention is the
      stapedectomy, where a small crook shaped piston is placed in the oval window of
      the cochlea and connected to the incus through crimping thus bypassing the
      diseased stapes. Performing the crimp process with the correct force is necessary
      since loose crimps poorly transmit sound whereas tight crimps will eventually
      result in necrosis of the incus. Clinically, demand is high to reproducibly
      conduct the crimp process through a precise force measurement. For this reason,
      we have developed a fiber Bragg grating (FBG) integrated microforceps for use in
      such interventions. This device was calibrated, and tested in cadaver
      preparations. With this instrument we were able to measure for the first time
      forces involved in crimping a stapes prosthesis to the incus. We also discuss a
      method of attaching and actuating such forceps in conjunction with a robot
      currently under development in our group. Each component of this system can be
      used separately or combined to improve surgical accuracy, confidence and outcome.

PMID- 21095679
TI  - Method to observe hemodynamic and metabolic changes during hemodiafiltration
      therapy with exercise.
AB  - Intradyalitic exercise programas are important to improve patient's hemodynamic
      stability. Blood pressure and metabolic changes are correlated when heat
      accumulation is due to increment of the body core temperature (+1.0  degrees C).
      However, increase in temperature could be controlled by lowering dialysate's
      temperature using two main modalities techniques (isothermic and thermoneural)
      with different patient's thermal balance consequences, not yet well studied. In
      this work, a new method to observe the main physiological parameters (hearth rate
      variability (HRV), blood pressure, BTM dialysate temperature control and
      substrate utilization by indirect calorimtery) which are involved in
      hemodiafitration (HDF), are displayd. An experiment was carried out in a group of
      5 patients waiting kidney transplant. In each patient, EE was assessed as well as
      the HRV during isothermic and thermoneutral modalities as a manner of cross and
      prospective study (a) at before therapy, (b) during therapy and (c) at the end of
      the HDF therapy. Power extraction was also measured by a BTM (Blood Temperature
      Monitor from Fresenius Inc), in order to determine how the dialysate temperature
      was controlled. The results showed important method's advantages which place the
      BTM performance as unstable control system with the possibility to produce
      undesirable HRV changes as the vagotonical response. However more patient cases
      are needed in order to identify the real advantage of this new method.

PMID- 21095681
TI  - A Gel filled intravaginal transducer for extended measurements of intra-abdominal
      pressure.
AB  - Limitations of the standard urogynecological pressure transducers have not
      adequately provided reliable measurements of intra-abdominal pressure (IAP)
      during physical activities. A previous novel intravaginal pressure transducer
      (IVT) was developed in order to overcome the shortcomings in existing technology.
      The design of the IVT was validated though comparisons with existing pressure
      transducers in both the clinical and bench top settings. However, a number of
      improvements were needed to overcome limitations in the previous design. A larger
      elastomeric capsule with transducer was developed and filled with silicone gel to
      replace the existing saline filled capsule and to better integrate proposed
      wireless technology. Impulse response and frequency testing were compared between
      the saline filled IVT and the new gel filled sensor and were found to be
      equivalent. Additional testing was performed on the gel filled device including
      drift and temperature measurements of sensitivity and offset. Results show the
      temperature coefficient of offset and sensitivity within correctible limitations
      with our proposed signal conditioner circuits.

PMID- 21095682
TI  - An insole sensor for recording weight bearing behavior during tibial fracture
      rehabilitation.
AB  - Partial weight bearing prescriptions for tibial fracture care are made with
      little data to support their efficacy. To provide long term tibial load data that
      can be used to study, guide, and monitor partial weight bearing, we developed a
      novel load sensor that can record the load placed on an injured limb over a two
      week period of time. The prototype load sensor demonstrated high linearity, low
      hysteresis and low static and dynamic drift. Preliminary human testing on the
      load sensor demonstrated the ability of the load sensor to capture load profile
      during underfoot recording. Presented are the bench testing and human testing
      data on the prototype load sensor verifying the design of an economic and durable
      system that allows for 2 weeks of recording of normal loads experienced by the
      tibia. This design motivates a next generation approach for use in clinical
      trials that will enable clinicians and researchers to improve current partial
      weight bearing prescriptions, thus improving tibial fracture outcomes.

PMID- 21095683
TI  - Relative to direct haptic feedback, remote vibrotactile feedback improves but
      slows object manipulation.
AB  - Most prosthetic hand users are limited to visual feedback of movement
      performance. To characterize the benefit of vibrotactile feedback for a task that
      lacks haptic feedback, a virtual environment was used to experimentally
      manipulate visual, task-relevant haptic, and remote vibrotactile feedback on
      simple object manipulation for unimpaired subjects. The combination of visual and
      remote vibrotactile feedback was compared to visual feedback alone, and to
      simultaneous visual and direct haptic feedback to represent ideal performance.
      Visual and vibrotactile feedback resulted in improvement of most performance
      variables including difficulty ratings relative to visual feedback alone. However
      addition of sensory cues to visual feedback increased trial times and the
      increase was steeper for vibrotactile than for haptic feedback. Specifically,
      during vibrotactile feedback the velocity did not change, but the duration of
      execution increased due to improved performance, resulting in increased trial
      times. This result suggests future exploration of performance improvement and
      execution speed for augmented sensory feedback.

PMID- 21095684
TI  - Effect of force feedback from each DOF on the motion accuracy of a surgical tool
      in performing a robot-assisted tracing task.
AB  - In robot-assisted surgery, it may be important to provide force feedback to the
      hand of the surgeon. Here we examine how force feedback from each degree of
      freedom (DOF) on a hand controller affects the motion accuracy of a surgical
      tool. We studied the motion accuracy of a needle-shaped tool in performing a
      robot-assisted tracing task. On a virtual simulation of the tool and neuroArm
      robot, human participants manipulated a hand controller to move the tool attached
      to the end-effector of the robot. They used the tool to trace a line on pipes
      (mimicking blood vessels) along 3 orthogonal directions, corresponding to 3 DOF
      on the hand controller. We observed that force feedback from each DOF on the hand
      controller had a significant effect on the motion accuracy of the tool during
      tracing. Varying force conditions yielded insignificant difference in motion
      accuracy. These results indicate a need of revising the hand controller for
      achieving improved motion accuracy in performing robot-assisted tasks.

PMID- 21095685
TI  - Learning kinematic mappings in laparoscopic surgery.
AB  - We devised an interactive environment in which subjects could perform simulated
      laparoscopic maneuvers, using either unconstrained movements or standard
      mechanical contact typical of a box-trainer. During training the virtual tool
      responded to the absolute position in space (Position-Based) or the orientation
      (Orientation-Based) of a hand-held sensor. Volunteers were further assigned to
      different sequences of target distances (Near-Far-Near or Far-Near-Far).
      Orientation-Based control produced much lower error and task times during
      training, which suggests that the motor system more easily accommodates tool use
      with degrees of freedom that match joint angles. When evaluated in constrained
      (physical box-trainer) conditions, each group exhibited improved performance from
      training. However, Position-Based training enabled greater reductions in movement
      error relative to Orientation-Based (mean -13.7%, CI:-27.1, -0.4). Furthermore,
      the Near-Far-Near schedule allowed a greater decrease in task time relative to
      the Far-Near-Far sequence (mean -13.5%, CI:-19.5, -7.5). Training at shallow
      insertion in virtual laparoscopy might promote more efficient movement strategies
      by emphasizing the curvature of tool motion. In addition, our findings suggest
      that an understanding of absolute tool position is critical to coping with
      mechanical interactions between the tool and trochar.

PMID- 21095686
TI  - Improving the management of chronic diseases using web-based technologies: an
      application in hemophilia care.
AB  - Modern methods of information and communication that use web technologies provide
      an opportunity to facilitate closer communication between patients and healthcare
      providers, allowing a joint management of chronic diseases. This paper describes
      a web-based technological solution to support the management of inherited
      bleeding disorders integrating, diffusing and archiving large sets of data
      relating to the clinical practice of hemophilia care, more specifically the
      clinical practice at the Hematology Service of Coimbra Hospital Center (a
      Hemophilia Treatment Center located in Portugal).

PMID- 21095687
TI  - A system for intelligent home care ECG upload and priorisation.
AB  - In this contribution, a system for internet based, automated home care ECG upload
      and priorisation is presented for the first time. It unifies the advantages of
      existing telemonitoring ECG systems adding functionalities such as automated
      priorisation and usability for home care. Chronic cardiac diseases are a big
      group in the geriatric field. Most of them can be easily diagnosed with help of
      an electrocardiogram. A frequent or long-term ECG analysis allows early diagnosis
      of e.g. a cardiac infarction. Nevertheless, patients often aren't willing to
      visit a doctor for prophylactic purposes. Possible solutions of this problem are
      home care devices, which are used to investigate patients at home without the
      presence of a doctor on site. As the diffusion of such systems leads to a huge
      amount of data which has to be managed and evaluated, the presented approach
      focuses on an easy to use software for ECG upload from home, a web based
      management application and an algorithm for ECG preanalysis and priorisation.

PMID- 21095688
TI  - Interoperable and standard e-Health solution over Bluetooth.
AB  - The new paradigm of e-Health demands open sensors and middleware components that
      permit transparent integration and end-to-end interoperability of new personal
      health devices. The use of standards seems to be the internationally adopted way
      to solve these problems. This paper presents the implementation of an end-to-end
      standards-based e-Health solution. This includes ISO/IEEE11073 standard for the
      interoperability of the medical devices in the patient environment and EN13606
      standard for the interoperable exchange of the Electronic Healthcare Record. The
      design strictly fulfills all the technical features of the most recent versions
      of both standards. The implemented prototype has been tested in a laboratory
      environment to demonstrate its feasibility for its further transfer to the
      healthcare system.

PMID- 21095689
TI  - A wireless blood pressure monitoring system for personal health management.
AB  - In this paper, we developed a wireless blood pressure monitoring system which
      provides a useful tool for users to measure and manage their daily blood pressure
      values. This system includes an ARM-based blood pressure monitor with a ZigBee
      wireless transmission module and a PC-based management unit with graphic user
      interface and database. The wireless blood pressure monitor can measure the blood
      pressure and heart rate and then store and forward the measuring information to
      the management unit through the ZigBee wireless transmission. On the management
      unit, user can easy to see their blood pressure variation in the past using a
      line chart. Accuracy of blood pressure measurement has been verified by a
      commercial blood pressure simulator and shown the bias of systolic blood pressure
      is <= 1 mmHg and the bias of diastolic blood pressure is <= 1.4 mmHg.

PMID- 21095690
TI  - Angelcare mobile system: homecare patient monitoring using bluetooth and GPRS.
AB  - The quick progress in technology has brought new paradigms to the computing area,
      bringing with them many benefits to society. The paradigm of ubiquitous computing
      brings innovations applying computing in people's daily life without being
      noticed. For this, it has used the combination of several existing technologies
      like wireless communications and sensors. Several of the benefits have reached
      the medical area, bringing new methods of surgery, appointments and examinations.
      This work presents telemedicine software that adds the idea of ubiquity to the
      medical area, innovating the relation between doctor and patient. It also brings
      security and confidence to a patient being monitored in homecare.

PMID- 21095691
TI  - A healthy lifestyle coaching-persuasive application for patients with type 2
      diabetes.
AB  - Losing weight can be one of the toughest objectives related to diabetes
      treatment, especially for Type 2 diabetes mellitus. This paper describes a tool
      to set goals to achieve lifestyle behavioral changes, and keep track of the
      benefits derived from these changes. This strategy leans on the capability of
      evaluating users' compliance to treatment, identifying key points where the lack
      of motivation causes therapy dropping, and on the better resources that
      physicians will have to adjust the treatments and the prescriptions.

PMID- 21095692
TI  - Body sway measurement for fall risk assessment using inexpensive webcams.
AB  - In this paper, we present a method for extracting body sway parameters from a
      three-dimensional voxel reconstruction, which is built using silhouettes captured
      from two calibrated web camera views. The results were validated with a Vicon
      motion capture system. Experiments were conducted in which subjects stand and
      sway in the anterior-posterior direction and then in the lateral directions with
      two different frequencies. In addition, experiments were also conducted where
      subjects walked in a straight path at different speeds. Through the experiment,
      the Vicon cameras recorded the motion of reflective markers attached to subjects,
      and our two calibrated cameras captured the images. Good agreement was found with
      our system compared to the Vicon results, given the limitation of voxel space
      resolution and frame rate. The development of this technology provides potential
      capability of measuring body sway in daily living environment for elderly people,
      and can be used as part of a balance, stability and fall risk assessment tool.

PMID- 21095693
TI  - Wavelet based time series forecast with application to acute hypotensive episodes
      prediction.
AB  - This paper presents a generic methodology for time series prediction, based on a
      wavelet decomposition/ reconstruction technique, together with a feedforward
      neural networks structure. The proposed methodology combines the flexibility and
      learning abilities of neural networks with a compact description of the signals,
      inherent to wavelets. In a first phase a wavelet decomposition of the signal is
      performed, providing a small number of coefficients that summarizes signal time
      evolution dynamics. The prediction problem is then effectively addressed by means
      of a neural networks model, previously trained using coefficients of the training
      dataset. The particular problem of forecasting acute hypotensive episodes (AHE)
      occurring in intensive care units was used to prove the effectiveness of the
      proposed strategy. The dataset, extracted from MIMIC-II, was made available in
      the context of the PhysioNet-Computers in Cardiology Challenge 2009. Results
      attained in this work were similar to the best ones achieved under that
      challenge.

PMID- 21095694
TI  - Using the Lomb periodogram for non-contact estimation of respiration rates.
AB  - We describe a contact-less method for measurement of respiration rate during
      sleep using a 5.8GHz radio-frequency bio-motion sensor. The sensor operates by
      sensing phase shifts in reflected radio waves from the torso caused by
      respiratory movements and other bodily movements such as twitches, positional
      changes etc. These non-respiratory motion artefacts can obscure reliable
      estimation of breathinig rates if conventional spectral analysis is used. This
      paper reports on the accuracy of the respiration rate estimates obtained via
      algorithmic approaches using Lomb-periodogram based analysis (which can deal with
      missing or corrupted data), as compared to conventional spectral analysis. Gold
      standard respiration rates are derived by expert scoring of respiration rates
      measured through polysomnography (PSG) from sensors (Respiratory Inductance
      Plethysmography (RIP) belts) in contact with the subject in an accredited sleep
      laboratory. Specifically, respiration rates for 15-minute segments chosen from 10
      subjects free of Sleep-Disorded Breathing (AHI<5) were selected for analysis in
      this paper. Comparison to the expert annotation indicates strong agreement, with
      the Lomb-periodogram respiration rates with the average error between the
      measurements being less than 0.4 breaths/min and a standard deviation of 0.3
      breaths/minute. Moreover, we showed that the proposed algorithm could track
      respiration rate over the complete night's recordings for those 10 subjects. We
      conclude that the non-contact biomotion sensor may provide a promising approach
      to continuous respiration rate monitoring of reasonable accuracy.

PMID- 21095695
TI  - Automated Levodopa-induced dyskinesia assessment.
AB  - An automated methodology for Levodopa-induced dyskinesia (LID) assessment is
      presented in this paper. The methodology is based on the analysis of the signals
      recorded from accelerometers and gyroscopes, which are placed on certain
      positions on the subject's body. The obtained signals are analyzed and several
      features are extracted. Based on these features a classification technique is
      used for LID detection and classification of its severity. The method has been
      evaluated using a group of 10 subjects. Results are presented related to each
      individual sensor as well as for various sensor combinations. The obtained
      results indicate high classification ability (93.73% classification accuracy).

PMID- 21095696
TI  - Localized fatigue effects on quiet standing control by fractional Brownian
      motion.
AB  - In this work, the anterior-posterior displacement of the center of pressure was
      modeled as a fractional Brownian motion to analyze the effect of fatigue of
      plantar flexor muscles by isometric contraction. A sample of 17 young, healthy
      adults was evaluated by stabilometric test, 2 min before and after a plantar
      flexion, sustained until exhaustion. For each test, the model was applied to four
      consecutive periods of 30 s and then averaged to estimate the parameters. The
      fatigue increased the stochastic activity in both persistent and antipersistent
      controls, and also increased the Hurst exponent of the long-term mechanism. As a
      conclusion, the used model suggests that peripheral fatigue increases the body
      sway and reduces the gain of the antipersistent mechanism. However, these changes
      are detectable only when more than one 30 s data segment is considered for
      analysis.

PMID- 21095697
TI  - An alternative approach in muscle fatigue evaluation from the surface EMG signal.
AB  - The aim of this study was to compare the intervals of time between adjacent zero
      crossings (ZCI), an alternative frequency-temporal parameter, with the root-mean
      square (RMS) value and the median frequency (F(med)) from the surface EMG (sEMG)
      signal in muscle fatigue analysis. Twenty right-handed volunteers performed
      isometric contractions of right biceps brachii muscle while sEMG signals were
      collected from it at three different and arbitrary load levels until fatigue. The
      mean ZCI presented a significant correlation with F(med) but not with RMS value
      and it also presented lower coefficients of variation than others. The results
      pointed that mean ZCI properties can contribute more than F(med) and RMS value on
      the interpretation of the muscle function under fatigue conditions.

PMID- 21095698
TI  - Vigilance detection based on sparse representation of EEG.
AB  - Electroencephalogram (EEG) based vigilance detection of those people who engage
      in long time attention demanding tasks such as monotonous monitoring or driving
      is a key field in the research of brain-computer interface (BCI). However, robust
      detection of human vigilance from EEG is very difficult due to the low SNR nature
      of EEG signals. Recently, compressive sensing and sparse representation become
      successful tools in the fields of signal reconstruction and machine learning. In
      this paper, we propose to use the sparse representation of EEG to the vigilance
      detection problem. We first use continuous wavelet transform to extract the
      rhythm features of EEG data, and then employ the sparse representation method to
      the wavelet transform coefficients. We collect five subjects' EEG recordings in a
      simulation driving environment and apply the proposed method to detect the
      vigilance of the subjects. The experimental results show that the algorithm
      framework proposed in this paper can successfully estimate driver's vigilance
      with the average accuracy about 94.22 %. We also compare our algorithm framework
      with other vigilance estimation methods using different feature extraction and
      classifier selection approaches, the result shows that the proposed method has
      obvious advantages in the classification accuracy.

PMID- 21095699
TI  - Ambulatory REACT: real-time seizure detection with a DSP microprocessor.
AB  - REACT (Real-Time EEG Analysis for event deteCTion) is a Support Vector Machine
      based technology which, in recent years, has been successfully applied to the
      problem of automated seizure detection in both adults and neonates. This paper
      describes the implementation of REACT on a commercial DSP microprocessor; the
      Analog Devices Blackfin(r). The primary aim of this work is to develop a
      prototype system for use in ambulatory or in-ward automated EEG analysis.
      Furthermore, the complexity of the various stages of the REACT algorithm on the
      Blackfin processor is analysed; in particular the EEG feature extraction stages.
      This hardware profile is used to select a reduced, platform-aware feature set, in
      order to evaluate the seizure classification accuracy of a lower-complexity,
      lower-power REACT system.

PMID- 21095700
TI  - Characterization of neurologic injury using novel morphological analysis of
      Somatosensory Evoked Potentials.
AB  - This paper describes an innovative, easy-to-interpret, clinically translatable
      tool for analysis of Somatosensory Evoked Potentials (SSEPs). Unlike traditional
      analysis, which involves peak-to-peak amplitude and latency calculation, this
      method, phase space analysis, analyzes the overall morphology of the SSEP, and
      includes greater information. The SSEP is plotted in phase space (x-dot vs. x),
      which leads to an approximately spiral curve. The area swept out by this curve is
      termed the Phase Space Area (PSA). As PSA calculation involves numerical
      differentiation, we present a comparison of two different approaches to combat
      noise amplification: finite-window smoothing, and total variation regularization
      (TVR) of the numerical derivative. These methods are applied to simulated SSEPs.
      The efficacy of these methods in performing noise-reduction is assessed and
      compared with ensemble averaging. While TVR gives a reasonably robust
      approximation of the derivative, Gaussian smoothing of the derivative offers the
      best trade-off between the number of signal sweeps required to be averaged, close
      approximation of the SSEP derivative, and optimal estimation of the PSA. We
      validate this method by analyzing non-characteristic SSEPs that have
      indistinguishable peaks as is frequently seen in cases of underlying neurologic
      injury such as hypoxic-ischemic encephalopathy.

PMID- 21095701
TI  - Complexity analysis of the uterine electromyography.
AB  - In respect to the main goal of our ongoing work for predicting preterm birth, we
      analyze in this paper the complexity of the uterine electromyography (EMG) by
      using the sample entropy (SampEn) algorithm. By considering recent methodological
      developments, we measure the SampEn over multiple scales using the wavelet packet
      decomposition method. The results obtained from the analyzed data indicate that
      SampEn decreases along pregnancy. Furthermore, we demonstrate that the computed
      SampEn parameter may discriminate between the two classes (pregnancy/labor). The
      results are supported by statistical analysis using t-test indicating good
      statistical significance with a confidence level of 95%. A surrogate data test is
      also performed to investigate the nature of the underlying dynamics of our
      experimental data. The results are very promising for monitoring pregnancy and
      detecting labor to help identify preterm labor.

PMID- 21095702
TI  - Band-phase-randomized surrogate data reveal high-frequency chaos in heart rate
      variability.
AB  - We propose a new band-phase-randomized surrogate data method to evaluate the
      chaotic dynamics in the high (HF) and low frequency (LF) bands of heart rate
      variability (HRV) in healthy subjects. The chaotic strength of normal HRV as
      assessed by a noise titration assay completely vanished when its power spectrum
      was phase-randomized over the entire frequency band or the HF band alone, but not
      the LF band alone. This finding confirms recent evidence that chaotic dynamics in
      normal HRV is ascribable mainly to the HF component, or respiratory sinus
      arrhythmia.

PMID- 21095703
TI  - Movement decoding from noninvasive neural signals.
AB  - It is generally assumed that noninvasively-acquired neural signals contain an
      insufficient level of information for decoding or reconstructing detailed
      kinematics of natural, multi-joint limb movements and hand gestures. Here, we
      review recent findings from our laboratory at the University of Maryland showing
      that noninvasive scalp electroencephalography (EEG) or magnetoencephalography
      (MEG) can be used to continuously decode the kinematics of 2D 'center-out'
      drawing, unconstrained 3D 'center-out' reaching and 3D finger gesturing. These
      findings suggest that these 'far-field', extra-cranial neural signals contain
      rich information about the neural representation of movement at the macroscale,
      and thus these neural representations provide alternative methods for developing
      noninvasive brain-machine interfaces with wide-ranging clinical relevance and for
      understanding functional and pathological brain states at various stages of
      development and aging.

PMID- 21095704
TI  - Compressed-sensing dynamic MR imaging with partially known support.
AB  - Compressed Sensing (CS) has recently been applied to dynamic MRI to improve the
      acquisition speed. Existing methods exploit the information that the dynamic
      images are sparse in the spatial and temporal-frequency (y-f) domain. In this
      paper, we propose to use the additional prior information in CS reconstruction
      that the support of y-f space is partially known from the motion pattern of
      dynamic MR images. The reconstruction is then formulated as a truncated l(1)
      minimization problem. Experimental results show that the dynamic image
      reconstruction quality of the proposed method is superior to that of existing
      methods when the same number of measurements is used.

PMID- 21095705
TI  - First-pass perfusion cardiac MRI using the Partially Separable Functions model
      with generalized support.
AB  - Dynamic imaging methods based on the Partially Separable Functions (PSF) model
      have been used to perform ungated cardiac MRI, and the critical parameter
      determining the quality of the reconstructed images is the order, L, of the PSF
      model. This work extends previous methods by increasing L in the cardiac region
      to improve the ability of the PSF model to represent complex spatiotemporal
      signals. The resulting higher order PSF model is fit to sparse (k, t)-space data
      using spatial-spectral support, spatial-eigenbasis support, and spectral sparsity
      constraints. This new method is demonstrated in the context of 2D first-pass
      perfusion MRI in a healthy rat heart.

PMID- 21095706
TI  - Quantification of DCE-MRI: pharmacokinetic parameter ratio between TOI and RR in
      reference region model.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed by
      obtaining sequential MRI images, before, during, and after the injection of a
      contrast agent. T(1) weighted MR imaging is used to observe the exchange of
      contrast agent between the vascular space and extravascular extracellular space
      (EES), providing information about blood volume and microvascular permeability.
      Signal intensity is obtained from the sequence of T(1) weighted images and then
      used to estimate the kinetic parameters in the equation derived from the
      pharmacokinetic model. In a DCE-MRI study, an accurate knowledge of the arterial
      input function (AIF) is very important to estimate the kinetic parameters.
      However, the AIF is usually unknown and it remains very difficult to obtain such
      information noninvasively. Here we use a reference region model that does not
      require the information about AIF. Though, this model usually needs literature
      value for the reference region. In this abstract, without knowledge of AIF,
      K(trans) in the tissue of interest (TOI) is compared with K(trans) in a reference
      region (RR). This was done by calculating the ratio K(R) between K(trans) in TOI
      and RR and the ratio V(R) between v(e) in TOI and RR while the K(trans,RR) was
      assigned a value ranging from 0.1 to 1.0. It is shown from both simulation and in
      vivo data set that this ratio is independent of K(trans,RR), implying we are no
      longer required to get the information about literature value for the reference
      region.

PMID- 21095707
TI  - Automated intracranial aneurysm isolation and quantification.
AB  - Until today, geometrical descriptors of intracranial aneurysms are largely used
      for diagnosis and treatment selection. Nevertheless, relatively little work has
      been devoted to automatize these measurements. In this work we propose a
      methodology for the automated isolation and quantification from vascular
      segmentation. The proposed methodology is based on skeleton topology analysis,
      geometrical analysis and deformable models to isolate, automatically, the
      aneurysm dome as well as its geometrical characteristics. The accuracy of this
      methodology when compared to manually isolated aneurysms is evaluated in 10
      patient-specific vascular geometries. Good correspondence is observed between
      manual and automated results.

PMID- 21095708
TI  - Pulse transit time variability analysis in an animal model of endotoxic shock.
AB  - The use of non-invasively measured pulse transit time (PTT) to monitor the
      cardiovascular systems in critically ill patients, like sepsis, can be of
      significant clinical value. In this study, the potential of PTT and its
      variability in cardiovascular system monitoring in a mechanically ventilated and
      anesthetized rabbit model of endotoxic shock was assessed. Eight adult New
      Zealand white rabbits, which were treated with endotoxin bolus infusion, were
      studied. Measurements of PTT, pre-ejection period (PEP), and vascular transit
      time (VTT) were obtained in pre- and post-intervention stages (before and 90
      minutes after the administration of endotoxin). The decrease in mean PTT (p <
      0.05) and PEP (p < 0.01) in the post-intervention stage reflected sympathetic
      activation, whilst the increase in respiratory variation in PTT (p < 0.01), PEP
      (p < 0.01), and VTT (p < 0.01) could be attributed to an enhancement of
      respiratory variation in stroke volume associated with hypovolemia in endotoxic
      shock. The relationship between beat-to-beat variability in PTT and all other
      cardiovascular time series were further investigated through linear regression
      analysis, which revealed that PTT was most strongly correlated with VTT (R(2) >=
      0.84 with positive slope). Computation of coherence and phase shift in the
      ventilating frequency band (HF: 0.50 - 0.75 Hz) showed that the respiratory
      variation in PTT was synchronized with both PEP and VTT (coherence > 0.84 with
      phase shift less than one cardiac beat). These results highlighted the potential
      value of PTT and its respiratory variation in characterizing the
      pathophysioloigcal hemodynamic change in endotoxic shock.

PMID- 21095709
TI  - Cardiovascular risk and status assessment.
AB  - This work focuses on the development of models to support the assessment of a
      patient's global cardiovascular condition. Three types of models, based on
      different types of information, have been developed: long term cardiovascular
      risk models, that evaluate the risk of occurring of cardiovascular event within a
      long period of time (years); short term cardiovascular risk models, to assess the
      risk of death within a short period of time (months); cardiovascular status
      assessment models, to estimate the current cardiovascular condition of a patient.
      Three major drawbacks of current cardiovascular tools are addressed: reduced
      number of risk factors considered by each individual tool, inappropriateness of
      these tools to incorporate empirical clinical expertise and incapacity of these
      tools to deal with incomplete information. Methodologies and preliminary results,
      obtained under FP7 HeartCycle project, as well as future directions of research
      are also presented in this paper.

PMID- 21095710
TI  - Effect of ECG quality measures on piecewise-linear trend detection for telehealth
      decision support systems.
AB  - Fledgling clinical decision support systems (DSSs) are being designed on the
      false assumption that consistent, good-quality signals are created in the
      unsupervised telehealth environment, but it has in fact been shown that signal
      quality is often very poor. Hence, it is important to investigate the detrimental
      impact of failing to recognize erroneous clinical parameter values. This study
      combines previous work in this area, related to artifact detection in
      electrocardiogram (ECG) signals, and piecewise-linear trend detection in
      longitudinal heart rate parameter records, to investigate the impact of choosing
      to ignore ECG signal quality prior to trend detection in the heart rate (HR)
      records. Using an artifact detection algorithm to improve the HR estimates from
      the ECG signals, when compared to reference HR values derived from human
      annotated 2453 ECGs from nine patients, resulted in a decrease in the estimation
      bias from 2.54 BPM (beat per minute) to 0.70 BPM and a decrease in the standard
      error from 0.47 BPM to 0.17 BPM. The application of the same artifact detection
      also results in a significant improvement in trend fitting, when compared to a
      fitting of the reference HR values, by reducing the mean RMSE value of the error
      in the trend fit from 2.14 BPM to 0.78 BPM and standard error from 0.49 BPM to
      0.10 BPM. As trend detection will be a component of future telehealth decision
      support systems, signal quality measures for unsupervised measurements are of
      paramount importance.

PMID- 21095711
TI  - Updating the biomedical engineering curriculum: Inclusion of Health Technology
      Assessment subjects.
AB  - This paper describes the work being carried out at Metropolitan Autonomous
      University (UAM) in Mexico City with regard to the continuous evaluation and
      updating of the Biomedical Engineering (BME) curriculum. In particular the
      courses regarded as part of the BME basic branch are reduced and new sets of
      elective subjects are proposed in order to bring closer the research work at UAM
      with the subjects in the BME curriculum. Special emphasis is placed on subjects
      dealing with Health Technology Assessment (HTA) and Health economics, as this
      branch of the BME discipline is quite promising in Mexico, but there are very few
      professionals in the field with adequate qualifications.

PMID- 21095712
TI  - Design and construction of a real simulator for calibrating lung servo
      ventilators.
AB  - This work shows the theoretical and practical development of a lung simulator for
      the calibration of Servoventilators of common use in health centers. It shows the
      development of a prototype device, Shown in the paper the formulation of a model
      to consider factors that exist in a human respiratory system in order to simulate
      normal and pathological conditions. Includes the calculation and construction of
      electronical and fluidic systems that were developed to set up an emulator that
      allows real lung adequate to connect with any type of servoventilator; as well as
      the results in terms of graphics of the required functions, highlighting the
      practical part that behaves like a real lung subsequently introduced into a torso
      anthropomorphic designed to better emulate real operating conditions of the lung
      embedded in a actual context closest to where the components behave as does the
      lung of a patient.

PMID- 21095713
TI  - Headset Bluetooth and cell phone based continuous central body temperature
      measurement system.
AB  - The accurate measure of the central temperature is a very important physiologic
      indicator in several clinical applications, namely, in the characterization and
      diagnosis of sleep disorders. In this paper a simple system is described to
      continuously measure the body temperature at the ear. An electronic temperature
      sensor is coupled to the microphone of a common commercial auricular Bluetooth
      device that sends the temperature measurements to a mobile phone to which is
      paired. The measurements are stored at the mobile phone and periodically sent to
      a medical facility by email or SMS (short messaging service).

PMID- 21095714
TI  - Patents on diagnostic methods in Europe under the European Patent Convention
      (EPC).
AB  - This article reviews the provisions of the European Patent Convention with regard
      to diagnostic methods practiced on the human or animal body. Moreover, it is also
      discussed the relevant jurisprudence (Case Law) interpreting the legal
      provisions. Some examples based on real cases are also presented and discussed.

PMID- 21095715
TI  - Performance of insole in reducing plantar pressure on diabetic patients in the
      early stages of the disease.
AB  - It has been well documented that subjects with peripheral neuropathy resulting
      from diabetes mellitus are at high risk of developing foot ulceration. Decreased
      sensation, in combination with high underfoot pressures, have been identified as
      prime etiology factors in the cause of plantar naturopathic ulceration [1]. This
      study presents the effect of four orthotic treatment techniques in reducing
      metatarsal head, heel and toes pressure during walking. A pressure measurement
      study was carried out on a diabetic patients group wearing four insoles,
      including the insole designed by the computer model proposed in this project. The
      aim of this study was to evaluate the effect on plantar pressure in diverse
      insoles prescribed and manufactured with various techniques on a random group of
      patients with diabetes mellitus in the early stages of the disease. Four types of
      insoles were designed and manufactured by methods available in the market; the
      computer model proposed on this project was used in order to design and
      manufacture the insole. The results show that every patient requires an
      individual assessment and often a personalized insole.

PMID- 21095716
TI  - Dynamic modeling and experimental results for a head tilt response.
AB  - The estimation of the vertical in humans is important in everyday life although
      the mechanisms involved are not completely understood yet. This paper presents
      two sets of experiments with normal subjects, using the same virtual reality
      setup, aiming to help in this understanding. First, a steady state experiment is
      presented, which is used to determine the gravitational vertical precision while
      the second, a dynamical transient response experiment, is used to find dynamic
      models of each subject response. Results show that the dynamic models are able to
      reproduce the results of the steady state experiment while having the benefits
      that a dynamic model brings to evaluate subjects performance.

PMID- 21095717
TI  - Active metabolic weight estimation using bioimpedance, indirect calorimetry and
      the clino-ortho maneuver.
AB  - The resting energy expenditure (REE) and substrate utilization are computed by
      indirect calorimetry technique (ICT). The REE represents 80-85% of the total
      energy expenditure (TEE) but only accounts for the 7% of the actual body weight
      (ABW). The TEE is produced by the organs plus muscles, whereas the REE accounts
      only for the main organs. An important problem comes up when the REE is computed
      throughout the fat free mass (FFM) computation or anthropometric measurements
      because they do not explain the tremendous catabolic variability by ICT when
      subjects show the same body composition. Therefore, the aim of this work is to
      develop a method to compute the metabolic active weight (MAW) as a new form that
      may help to understand the catabolic activity of the body composition. The
      premise was the clino-ortho maneuver can split the ABW in two parts: one in which
      the MAW reflects the FFM catabolism while the second part was not considered
      since there is not energy requirement in it. The experiment design studied 37
      young volunteers undergoing the clino-ortho maneuver during fast and postprandial
      conditions. The results showed REE increments of 21% during phase I (fast), while
      in phase II (postprandial) only 14% was achieved in ortho-postprandial.
      Therefore, the computed MAWs were 65.5Kg and 58Kg, respectively, when the ABW
      average was 70 Kg and the FFM was 50 Kg. One first conclusion was that the 15.5
      Kg of the MAW above the FFM could explain a catabolic equivalence which can be
      exclusively related to the fast-ortho position which can help to classify
      exclusively the dynamic over activity of the FFM.

PMID- 21095718
TI  - An evaluation of passive properties of spastic muscles in hemiparetic stroke
      survivors.
AB  - We have reported earlier [1] a new method for estimating reflex threshold in
      spastic muscles of stroke survivors, using controlled amplitude taps superimposed
      on progressive and controlled muscle indentation of the bicipital tendon in the
      bicipital fossa. This muscle indentation is done with a linear actuator
      positioned over the biceps muscle tendon at the elbow. In the course of testing
      for increased stretch reflex responses, (a cardinal feature of spasticity), we
      have also observed that the intrinsic or passive stiffness of the muscle is often
      increased. This assessment is derived from recordings of the force generated by
      the tendon during progressive loading, and by the instantaneous force response to
      the tendon tap. Thus, it appears that passive properties of muscle are often also
      changed in parallel with the reflex abnormalities. While some of these mechanical
      features have been described in earlier studies of torque-angle relations of
      spastic joints, it appears that these features can also be recognized readily
      using a small actuator that loads the tendon progressively. These findings may
      help clinicians recognize early changes in muscle mechanical properties, and may
      help them prevent large-scale adverse changes in muscle function.

PMID- 21095719
TI  - Global solution of the finite element shape-from-shading model with a
      bioluminescent molecular imaging application.
AB  - Only a planar bioluminescence image acquired from an ordinary cooled charge
      coupled device (CCD) array every time, how to re-establish the three-dimensional
      small animal shape and light intensity distribution on the surface has become
      urgent to be solved as a bottleneck of bioluminescence tomography (BLT)
      reconstruction. In this paper, a finite element algorithm to solve the Dirichlet
      type problem for the first order Hamilton-Jacobi equation related to the shape
      fromshading model is adopted. The algorithm outputting the globally maximal
      solution of the above problem avoids cumbersome boundary conditions on the
      interfaces between light and shadows and the use of additional information on the
      surface. The results of the optimization method are satisfied. It demonstrates
      the feasibility and potential of the finite element shape-fromshading (FE-SFS)
      model for reconstructing the small animal surface that lays one of key
      foundations for a fast low-cost application of the BLT in the next future.

PMID- 21095720
TI  - Multimodal multidimensional imaging for visual system status assessment.
AB  - Non-invasive optical methods that enable in vivo or in situ visualization of
      tissue components are of particular relevance in ophthalmology, as they can
      provide key information about the relationship between the structure and function
      of the visual system. In this paper we present a semiautomated multimodal imaging
      tool for co-registration of images of retinal structure and its function, based
      on point correspondence. Decision support analysis was applied to define
      significant features for the multimodal mapping system, using a set of 1500
      subjects who were affected by blindness associated hereditary retinal
      dystrophies. Additionally, the developed software was tested by two experienced
      observers using data from 25 subjects. Inter-observer and intra-observer
      reliability was determined. We conclude that semi-automated multimodal mapping
      could be a promising new tool for an individualized visual system status
      assessment that can be applied for the early diagnosis of blindness associated
      diseases. Moreover, this mapping approach should prove particularly appropriate
      for studying pathophysiology in inherited blindness associated diseases.

PMID- 21095721
TI  - Anomalous diffusion of kv2.1 channels observed by single molecule tracking in
      live cells.
AB  - Kv2.1 are voltage gated potassium channels that form long-lived clusters on the
      surface of mammalian cells. We have used single molecule tracking to study the
      interesting dynamics of these channels in live HEK cells. Both the channels
      inside the clusters and non-clustering channels are found to follow anomalous
      subdiffusion. The effect of actin cytoskeleton on the diffusion properties of the
      channels is also investigated in the presence of cytochalasin D, a F-actin
      binding drug that blocks actin polymerization.

PMID- 21095722
TI  - An efficient global inexact Newton method regularized by a dynamic sparse term
      for in vivo tomographic bioluminescence imaging.
AB  - Tomographic bioluminescence imaging suffers from poor imaging robustness, since
      it is severely affected by selection of regularization parameter (RP) and
      initialization for source distribution. In this paper, a global-inexact-Newton
      based reconstruction methodology, which is regularized by a dynamic sparse term,
      is demonstrated for in vivo tomographic imaging. The novel method can enhance
      higher imaging reliability and efficiency. Mouse experimental reconstructions
      were performed to validate the proposed method. These results demonstrate that
      the source distribution can be accurately located over a wide range of values of
      RP and iteration initializations. Moreover, the reconstruction efficiency was
      also studied.

PMID- 21095723
TI  - Automatic detection of Schwalbe's line in the anterior chamber angle of the eye
      using HD-OCT images.
AB  - Angle-closure glaucoma is a major cause of blindness in Asia and could be
      detected by measuring the anterior chamber angle (ACA) using gonioscopy,
      ultrasound biomicroscopy or anterior segment (AS) optical coherence tomography
      (OCT). The current software in the VisanteTM OCT system by Zeiss is based on
      manual labeling of the scleral spur, cornea and iris and is a tedious process for
      ophthalmologists. Furthermore, the scleral spur can not be identified in about
      20% to 30% of OCT images and thus measurements of the ACA are not reliable.
      However, high definition (HD) OCT has identified a more consistent landmark:
      Schwalbe's line. This paper presents a novel algorithm which automatically
      detects Schwalbe's line in HD-OCT scans. The average deviation between the values
      detected using our algorithm and those labeled by the ophthalmologist is less
      than 0.5% and 0.35% in the horizontal and vertical image dimension, respectively.
      Furthermore, we propose a new measurement to quantify ACA which is defined as
      Schwalbe's line bounded area (SLBA).

PMID- 21095724
TI  - Time-domain Optical Coherence Tomography system with integrated delay line for
      surgical guidance applications.
AB  - Optical Coherence Tomography is a high resolution imaging technique able to
      provide in-depth information about living tissue. Among all its applications, it
      can be argued that surgical guidance is one of the most demanding in terms of
      system reliability, footprint and cost. In order to enable faster adoption of
      this technology in that field, we had already developed and demonstrated a new
      type of scanning delay line based on the thermo-optic effect of silicon. By
      changing the temperature of an integrated waveguide, we are able to produce a
      variation in optical delay. In this paper, we demonstrate the inclusion of such a
      device in a complete system and the performance levels that can be achieved with
      this technique. In particular, we show a line scan rate of 2kHz with good
      linearity and a scan range of 0.95mm in air. These values meet the needs of most
      surgical guidance applications.

PMID- 21095725
TI  - Terahertz sensing of corneal hydration.
AB  - An indicator of ocular health is the hydrodyanmics of the cornea. Many corneal
      disorders deteriorate sight as they upset the normal hydrodynamics of the cornea.
      The mechanisms include the loss of endothelial pump function of corneal
      dystophies, swelling and immune response of corneal graft rejection, and
      inflammation and edema, which accompany trauma, burn, and irritation events. Due
      to high sensitivity to changes of water content in materials, a reflective
      terahertz (300 GHz and 3 THz) imaging system could be an ideal tool to measure
      the hydration level of the cornea. This paper presents the application of THz
      technology to visualize the hydration content across ex vivo porcine corneas. The
      corneas, with a thickness variation from 470 - 940 um, were successfully imaged
      using a reflective pulsed THz imaging system, with a maximum SNR of 50 dB. To our
      knowledge, no prior studies have reported on the use of THz in measuring
      hydration in corneal tissues or other ocular tissues. These preliminary findings
      indicate that THz can be used to accurately sense hydration levels in the cornea
      using a pulsed, reflective THz imaging system.

PMID- 21095726
TI  - Early detection of disease-oriented state from hyperspectral tongue images with
      principal component analysis and vector rotation.
AB  - In this article, we propose an effective colorprocessing algorithm to analyze the
      hyperspectral image of the tongue and its application to preventive medicine by
      the concept of Japanese traditional herbal medicine (Kampo medicine). Kampo
      medicine contains a number of concepts useful for preventive medicine such as
      "Mibyou" - disease-oriented state - signs of abnormalities. Hyperspectral images
      of the tongue were taken with the system with an integrating sphere, and tongue
      area without coating was eliminated automatically. Then, spectral information of
      the tongue area without coating was analyzed by principal component analysis, and
      the component vector best representing the clinical symptom was found by rotating
      the vector on a plane spanned by two arbitrary principal component vectors.

PMID- 21095727
TI  - Comparative analysis of various brain imaging techniques.
AB  - The bio-imaging techniques have widespread applications from diagnosing diseases
      to investigating the body tissues at the cells level. Traditionally, these
      techniques were used mainly in the orthopedic treatment. However, with the
      development of infrared cameras, ultrasound, and radio wave technology, they are
      used in different medical fields such as cardiovascular analysis, neurological
      treatment and infant care. This paper reviews the common bio-imaging techniques
      used in the brain imaging and compares them based on resolution, contrast,
      biological risks involved, and price.

PMID- 21095728
TI  - An optical-parameters-free method for locating light source in deep tissue.
AB  - Bioluminescence of luciferase-expressing cells in live animals is a promising
      technique for image guided tumor resection. However, requiring exact optical
      tissue parameters is an underlying problem of diffusion equation when recovering
      bioluminescent images of luciferase activity within a volume using emission
      optical signal data from internal light sources. In this paper, an equivalence
      method based on the equation of radiative transfer (ERT) is proposed to locate
      bioluminescence source without optical tissue parameters. The solution of
      equivalence method is satisfied with the unique of localization as well as the
      complex tissue environment. The reconstructed images of bioluminescence are
      presented with simulated heterogeneous tissue models, and an 8.7% relative error
      of the source localization is obtained.

PMID- 21095729
TI  - Corneal graft detection for Descemet's stripping automated endothelial
      keratoplasty using optical coherence tomography.
AB  - The cornea is the window of the eye and when it is severely damaged or diseased,
      vision is impaired. Descemet's Stripping Automated Endothelial Keratoplasty
      (DSAEK) is a surgical procedure to replace the malfunctioned Descemet's membrane
      with a healthy one in order to restore the patient's sight. After the operation,
      ophthalmologists need to monitor the grafted membrane to check for signs of
      detachment, rejection, etc. and take appropriate actions before graft failure
      occurs. In this paper, we introduce the COrneaL GrAft Thickness Evaluation
      (COLGATE) System that we developed for ophthalmologists for the evaluation of the
      transplanted corneal graft. We discuss the various components in our system and
      methods we developed. Experiments are conducted and the results are m1 = 7.5% and
      m2 = 7.2%.

PMID- 21095730
TI  - Evaluation of autofocus functions of conventional sputum smear microscopy for
      tuberculosis.
AB  - This article presents a systematic analysis of focus functions in conventional
      sputum smear microscopy for tuberculosis. This is the first step in the
      development of automatic microscopy. Nine autofocus functions are analyzed in a
      set of 1200 images with varying degrees of content density. These functions were
      evaluated using quantitative procedures. The main accomplishment of this work was
      to show that an autofocus function based on variance measures produced the best
      results for tuberculosis images.

PMID- 21095731
TI  - Towards a versatile automated cell-detection system for science and diagnostics.
AB  - Analyzing in-situ tissue structures with complex shapes and textures such as
      multinuclear cells or cells without nuclei is still a challenge for currently
      available imageprocessing software. This work aims to provide a versatile system
      to solve such tasks provided that the structures of interests were detected by
      immunofluorescence microscopy. Images were automatically acquired using slide
      based microscopy. Human domain-experts manually marked up tissue samples to
      evaluate the performance of the computer generated masks. From precision and
      recall a balanced F-score was computed to measure the correlation between experts
      and algorithm output. Exhaustive parameter optimization was conducted to ensure
      that the optimal input parameters were applied during evaluation of the developed
      algorithm. This procedure significantly increased the performance compared to
      manually chosen input parameters. We present an approach that can handle huge
      tissue areas and does not rely on nuclei detection. Once a markup has been
      created, the algorithm can be parameter-optimized on ground-truth data for the
      chosen tissue sample. Thereafter, the resulting settings could be applied
      automatically to the respective stitched image. Concluding, we provide new
      insights in physiological and pathopysiological cellular mechanisms by automating
      the in-situ analysis of proteins in intact tissues.

PMID- 21095732
TI  - In vivo imaging of retinal gliosis: a platform for diagnosis of PD and Screening
      of anti-PD compounds.
AB  - Parkinson's disease (PD) is the second most frequent degenerative disorder after
      Alzheimer's disease. It is characterized by the depletion of mesenchephalic
      dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and
      striatal dopamine. Oxidative stress plays a major role in the pathogenesis of
      Parkinson's disease where DA neurons are especially vulnerable to excessive
      production of the H2O2 reactive oxygen species. Unfortunately, the first clinical
      symptoms of PD occur after at least 60-80% of nigro-striatal dopaminergic neurons
      have lost their function. Therefore, early detection of PD is critical in slowing
      down the progression of the disease and enabling the development of therapeutic
      compounds which could intervene at an earlier stage. Here, we employ in vivo
      molecular imaging of astrocytic retinal gliosis in a transgenic mice to
      longitudinally monitor the progression of MPTP-induced PD. We have quantitatively
      evaluated, via this imaging platform, the efficacy of a synthetic antioxidant,
      1,3- bisbenzylimidazolium bromide (DBZIM), in protecting the DA neurons and
      scavenging the ROS. We show here that MPTPinduced PD results in an upregulation
      of glial fibrillary acidic protein (GFAP), a marker for gliosis, by 36% relative
      to saline whereas gliosis is normalized in MPTP-induced PD mice treated with
      DBZIM.

PMID- 21095733
TI  - Probing sepsis and sepsis-like conditions using untargeted SPIO nanoparticles.
AB  - Sepsis is the leading cause of death in critically ill patients in the United
      States. Current diagnosis of sepsis relies heavily on the patient's manifestation
      of septic symptoms, which occur at life-threatening late stage of sepsis. Because
      the underlying biological changes of sepsis occur hours to days before the
      clinical presentation of symptoms, early detection of the biological changes will
      provide crucial opportunities for early diagnosis and effective treatment of
      sepsis. As an candidate for early sepsis detection, we propose using a novel
      quantitative susceptibility mapping (QSM) MRI that quantifiably measure the
      activity of the immune system during sepsis progression. It has been observed
      that Kupffer cells, comprising 80% of the liver's macrophages, play a pivotal
      role in the early response to system infection, a condition characteristic of
      sepsis. Further, it has been observed that phagocytosis by Kupffer cells is a
      major mechanism by which nanoparticle-based contrast agents, such as Feridex, are
      cleared from the body. By quantifying the amount of superparamagnetic iron-oxide
      nanoparticles uptaken by these macrophages and correlating this result to immune
      system response and the progression of sepsis, we can utilize commonly used
      contrast agents as markers in monitoring and diagnosing sepsis condition. This
      study offers an in vitro proof of concept; RAW264.7 murine monocytes were treated
      with lipopolysaccharide to induce a sepsis-like cell condition, incubated with
      the FDA-approved contrast agent Feridex IV, and imaged using QSM MRI for the
      quantification of iron.

PMID- 21095734
TI  - New reconstruction method of magnetoacoustic tomography with magnetic induction.
AB  - Image reconstruction is the key problem of MAT-MI. At present, there are certain
      problems for the images reconstruction methods which based on the divergence of
      Lorentz force, therefore, a new reconstruction method which based on the Lorentz
      force instead of its divergence is proposed in this paper. The singularity on the
      interface can be avoided, and it is possible to reconstruct the conductivity of
      imaging object directly without boundarypeak- noise on the reconstruction images.
      In order to test the validity of the new method, models of different structure
      were analyzed through numerical analysis, and the availability of the method was
      demonstrated.

PMID- 21095735
TI  - ORIGA(-light): an online retinal fundus image database for glaucoma analysis and
      research.
AB  - Retinal fundus image is an important modality to document the health of the
      retina and is widely used to diagnose ocular diseases such as glaucoma, diabetic
      retinopathy and age-related macular degeneration. However, the enormous amount of
      retinal data obtained nowadays mostly stored locally; and the valuable embedded
      clinical knowledge is not efficiently exploited. In this paper we present an
      online depository, ORIGA(-light), which aims to share clinical groundtruth
      retinal images with the public; provide open access for researchers to benchmark
      their computer-aided segmentation algorithms. An in-house image segmentation and
      grading tool is developed to facilitate the construction of ORIGA(-light). A
      quantified objective benchmarking method is proposed, focusing on optic disc and
      cup segmentation and Cup-to-Disc Ratio (CDR). Currently, ORIGA(-light) contains
      650 retinal images annotated by trained professionals from Singapore Eye Research
      Institute. A wide collection of image signs, critical for glaucoma diagnosis, are
      annotated. We will update the system continuously with more clinical ground-truth
      images. ORIGA(-light) is available for online access upon request.

PMID- 21095736
TI  - Content Based medical image retrieval based on BEMD: optimization of a similarity
      metric.
AB  - Most medical images are now digitized and stored in patients files databases. The
      challenge is how to use them for acquiring knowledge or/and for aid to diagnosis.
      In this paper, we address the challenge of diagnosis aid by Content Based Image
      Retrieval (CBIR). We propose to characterize images by using the Bidimensional
      Empirical Mode Decomposition (BEMD). Images are decomposed into a set of
      functions named Bidimensional Intrinsic Mode Functions (BIMF). Two methods are
      used to characterize BIMFs information content: the Generalized Gaussian density
      functions (GGD) and the Huang-Hilbert transform (HHT). In order to enhance
      results, we introduce a similarity metric optimization process: weighted
      distances between BIMFs are adapted for each image in the database. Retrieval
      efficiency is given for different databases (DB), including a diabetic
      retinopathy DB, a mammography DB and a faces DB. Results are promising: the
      retrieval efficiency is higher than 95% for some cases.

PMID- 21095737
TI  - Automatic detection of luminal borders in IVUS images by magnitude-phase
      histograms of complex brushlet coefficients.
AB  - We present a new technique to delineate lumen borders in intravascular ultrasound
      (IVUS) volumes of images acquired with a high-frequency Volcano (Rancho Cordova,
      CA) 45MHz transducer. Our technique relies on projection of IVUS sub-volumes onto
      orthogonal directional brushlet functions. Through selective projection of IVUS
      sub-volumes images and their Fourier transforms, tissue-specific backscattered
      magnitudes and phases identified within brushlet coefficients. We take advantage
      of such characteristics and construct 2.5-dimensional (2.5-D) magnitudes-phase
      histograms of coefficients in the transformed complex brushlet domain that
      contain distinct peaks corresponding to blood and non-blood regions. We exploit
      these peaks to mask out coefficients that represent blood regions and ultimately
      detect the luminal border after spatial regularization employing a parametric
      deformable model. We quantify our results by comparing them to manually traced
      borders by an expert on 2 datasets, containing 108 frames. We show that our
      approach is well suited for isolating coherent (i.e. plaque) structures from
      incoherent (i.e. blood) ones in IVUS pullbacks and detecting the lumen border, a
      challenging problem particularly in images acquired with high frequency
      transducers.

PMID- 21095738
TI  - In vitro evaluation of surface based non-invasive breast cancer screening with
      digital image based Elasto tomography (DIET).
AB  - Digital Image-based Elasto Tomography (DIET) is a non-invasive breast cancer
      screening modality that induces vibrations into a breast and images its surface
      motion with digital cameras. Disturbances in the motion are caused by areas of
      higher stiffness within the breast, potentially cancerous tumors. A concept is
      presented to detect the angular location of a tumor by analyzing the phase delay
      of the vibrations on the surface. The approach is verified experimentally on
      silicone phantom breasts with stiffer inclusions ranging from 0-32 mm. A strong
      signal differentiating healthy and cancerous phantoms can be seen at the second
      modal frequency of the breast, clearly detecting a 10 mm tumor. This approach
      offers great potential for this low cost and accessible breast cancer screening,
      as an adjunct to existing modalities.

PMID- 21095739
TI  - Dijkstra's algorithm applied to 3D skeletonization of the brain vascular tree:
      evaluation and application to symbolic.
AB  - This paper describes the methodology and the evaluation of a 3D skeletonization
      algorithm applied on brain vascular structure. This method is based on the
      application of the minimum cost-spanning tree using Dijkstra's algorithm and
      seems well appropriate to tubular objects. We briefly describe the different
      steps, from the segmentation to the skeleton analysis. Besides, we propose an
      original evaluation scheme of the method based on digital phantom and clinical
      data. The final aim of this work is to provide a symbolic description framework
      applied to cerebro-vascular structures.

PMID- 21095740
TI  - Multiple kernel learning for classification of diffuse lung disease using HRCT
      lung images.
AB  - A novel algorithm is presented for classification of four patterns of diffuse
      lung disease: normal, emphysema, honeycombing and ground glass opacity, on the
      basis of textural analysis of high resolution computed tomography (HRCT) lung
      images. The algorithm incorporates scale-space features based on Gaussian
      derivative filters and multi-dimensional multi-scale features based on wavelet
      and contourlet transforms of the original images. The mean, standard deviation,
      skewness and kurtosis along with generalized Gaussian density are used to model
      the output of filters and transforms, and construct feature vectors. Multi-class
      multiple kernel learning (m-MKL) classifier is used to evaluate the performance
      of the feature extraction scheme. The method is tested on a collection of 89
      slices from 38 patients, each slice of size 512*512, 16 bits/pixel in DICOM
      format. The dataset contains 70,000 ROIs from slices already marked by
      experienced radiologists. The average sensitivity and specificity achieved is
      94.16% and 98.68%, respectively.

PMID- 21095741
TI  - Preliminary Monte Carlo study of (18)F-FDG SPECT imaging with LaBr(3):Ce Crystal
      based Gamma Cameras.
AB  - The utility of (18)F-deoxyglucose ((18)F-FDG) in oncology, cardiology, and
      neurology has generated great interest in a more economical ways of imaging (18)F
      FDG than conventional PET scanners. The main thrust of this work is to
      investigate the potential use of LaBr(3):Ce materials in a low-cost FDG-SPECT
      system compared to NaI(Tl) using GATE Monte Carlo simulation. System performance
      at 140 keV and 511 keV was assessed using energy spectra, system sensitivity and
      count rate performance. Comparison of the LaBr(3):Ce and NaI(Tl) crystal-based
      systems showed 4.5% and 8.9% higher system sensitivity for the LaBr(3):Ce at 140
      keV and 511 keV, respectively. The LaBr(3):Ce scintillator significantly improves
      intrinsic count rate performance due to its fast decay time with respect to
      NaI(Tl). In conclusion, because LaBr(3):Ce crystal combines excellent intrinsic
      count rate performance with slightly increased system sensitivity, it has the
      potential to be used for (18)F-FDG -SPECT systems.

PMID- 21095743
TI  - Segmentation of small animal PET/CT mouse brain scans using an MRI-based 3D
      digital atlas.
AB  - The work reported in this paper aimed at developing and testing an automated
      method to calculate the biodistribution of a specific PET tracer in mouse brain
      PET/CT images using an MRI-based 3D digital atlas. Surface-based registration
      strategy and affine transformation estimation were considered. Such an approach
      allowed overcoming the lack of anatomical information in the inner regions of
      PET/CT brain scans. Promising results were obtained in one mouse (on two scans)
      and will be extended to a neuroinflammation mouse model to characterize the
      pathology and its evolution. Major improvements are expected regarding
      automation, time computation, robustness and reproducibility of mouse brain
      segmentation. Due to its generic implementation, this method could be
      successfully applied to PET/CT brain scans of other species (rat, primate) for
      which 3D digital atlases are available.

PMID- 21095742
TI  - Dental implant examination based on the log-polar matching of the maxillary
      radiograph images in the anisotropic scale space.
AB  - In this paper a computer vision system is proposed for automatic examination of
      implant placements based on the maxillary radiograph images. To find rotated and
      scale changed implants the system does template matching in the extended log
      polar space. Matching is proposed to be performed in the anisotropic scale-space,
      starting from the coarse level. The precise location of an implant is then
      refined based on the fine level of this space. The two processes are additionally
      controlled by the contour images which delineate exact positions of implants and
      other dental works.

PMID- 21095744
TI  - Towards respiration management in radiation treatment of lung tumors:
      transferring regions of interest from planning CT to kilovoltage X-ray images.
AB  - Tracking of lung tumors is imperative for improved radiotherapy treatment.
      However, the motion of the thoracic organs makes it a complicated task. 4D CT
      images acquired prior to treatment provide valuable information regarding the
      motion of organs and tumor, since it is manually annotated. In order to track
      tumors using treatment-day X-ray images (kV images), we need to find the
      correspondence with CT images so that projection of tumor region of interest will
      provide a good estimate about the position of the tumor on the X-ray image. In
      this study, we propose a method to estimate the alignment and respiration phase
      corresponding to X-ray images using 4D CT data. Our approach generates Digitally
      Reconstructed Radiographs (DRRs) using bilateral filter smoothing and computes
      rigid registration with kV images since the position and orientation of patient
      might differ between CT and treatment-day image acquisition processes. Instead of
      using landmark points, our registration method makes use of Kernel Density
      Estimation over the edges that are not affected much by respiration. To estimate
      the phase of X-ray, we apply template matching techniques between the lung
      regions of X-ray and registered DRRs. Our approach gives accurate results for
      rigid registration and provides a starting point to track tumors using the X-ray
      images during the treatment.

PMID- 21095745
TI  - TMS modeling toolbox for realistic simulation.
AB  - Transcranial magnetic stimulation (TMS) is a technique for brain stimulation
      using rapidly changing magnetic fields generated by coils. It has been
      established as an effective stimulation technique to treat patients suffering
      from damaged brain functions. Although TMS is known to be painless and
      noninvasive, it can also be harmful to the brain by incorrect focusing and
      excessive stimulation which might result in seizure. Therefore there is ongoing
      research effort to elucidate and better understand the effect and mechanism of
      TMS. Lately Boundary element method (BEM) and Finite element method (FEM) have
      been used to simulate the electromagnetic phenomenon of TMS. However, there is a
      lack of general tools to generate the models of TMS due to some difficulties in
      realistic modeling of the human head and TMS coils. In this study, we have
      developed a toolbox through which one can generate high-resolution FE TMS models.
      The toolbox allows creating FE models of the head with isotropic and anisotropic
      electrical conductivities in five different tissues of the head and the coils in
      3D. The generated TMS model is importable to FE software packages such as ANSYS
      for further and efficient electromagnetic analysis. We present a set of
      demonstrative results of realistic simulation of TMS with our toolbox.

PMID- 21095746
TI  - Automatic segmentation of the spinal cord and the dural sac in lumbar MR images
      using gradient vector flow field.
AB  - A Computer-aided diagnosis (CAD) system aims to facilitate characterization and
      quantification of abnormalities as well as minimize interpretation errors caused
      by tedious tasks of image screening and radiologic diagnosis. The system usually
      consists of segmentation, feature extraction and diagnosis, and segmentation
      significantly affects the diagnostic performance. In this paper, we propose an
      automatic segmentation method that extracts the spinal cord and the dural sac
      from T2-weighted sagittal magnetic resonance (MR) images of lumbar spine without
      the need of any human intervention. Our method utilizes a gradient vector flow
      (GVF) field to find the candidate blobs and performs a connected component
      analysis for the final segmentation. MR Images from fifty two subjects were
      employed for our experiments and the segmentation results were quantitatively
      compared against reference segmentation by two medical specialists in terms of a
      mutual overlap metric. The experimental results showed that, on average, our
      method achieved a similarity index of 0.7 with a standard deviation of 0.0571
      that indicated a substantial agreement. We plan to apply this segmentation method
      to computer-aided diagnosis of many lumbar-related pathologies.

PMID- 21095747
TI  - Segmenting echocardiography images using B-Spline snake and active ellipse model.
AB  - In this paper, a fully automated method for segmenting Left Ventricle (LV) in
      echocardiography images is proposed. A new method named active ellipse model is
      developed to automatically find the best ellipse inside the LV chamber without
      intervention of any specialist. A modified B-Spline Snake algorithm is used to
      segment the LV chamber in which the initial contour is formed by the predefined
      ellipse. As a result of using active ellipse model, the segmentation is
      extricated from dealing with gaps within myocardium boundary which are highly
      problematic in echocardiography image segmentation. Based on the results obtained
      from different studies, the proposed method is faster and more accurate than
      previous approaches. Our method is evaluated on 20 sets of echocardiography
      images of patients; and acquired results (92.30 +/- 4.45% dice's coefficient)
      indicate the proposed method has remarkable performance.

PMID- 21095748
TI  - Vessel network detection using contour evolution and color components.
AB  - Automated retinal screening relies on vasculature segmentation before the
      identification of other anatomical structures of the retina. Vasculature
      extraction can also be input to image quality ranking, neovascularization
      detection and image registration. An extensive related literature often excludes
      the inherent heterogeneity of ophthalmic clinical images. The contribution of
      this paper consists in an algorithm using front propagation to segment the vessel
      network, including a penalty on the wait queue to the fast marching method, which
      minimizes leakage of the evolving boundary. The algorithm requires no manual
      labeling of seeds, a minimum number of parameters and it is capable of segmenting
      color ocular fundus images in real scenarios, where multi-ethnicity and
      brightness variations are parts of the problem.

PMID- 21095749
TI  - Ultrafast method for mapping local functional connectivity hubs in the human
      brain.
AB  - Brain networks with energy-efficient hubs might support the high cognitive
      performance of humans and a better understanding of their organization is of
      relevance not only for studying normal brain development and plasticity but also
      neuropsychiatric disorders. Here we propose an ultra-fast method to map the
      distribution of the functional connectivity density (FCD) in the human brain. The
      method was tested in 972 subjects from a large repository of magnetic resonance
      imaging (MRI) time series collected in resting conditions. Consistently across
      research sites, a region located in the ventral precuneus was the area with the
      highest FCD, which suggest that this is a prominent functional hub in the brain.
      In addition regions located in the paracentral lobule, cuneus, inferior parietal,
      and posterior cingulate cortices had localized high FCD, suggesting that these
      regions also include prominent functional connectivity hubs.

PMID- 21095750
TI  - PDE-based reconstruction of the cerebral cortex from MR images.
AB  - The topologically correct and geometrically accurate reconstruction of the
      cerebral cortex from magnetic resonance (MR) images is an important step in
      quantitative analysis of the human brain structure, e.g. in cortical thickness
      measurement studies. Limited resolution of MR images, noise, intensity
      inhomogeneities, and partial volume effects can all contribute to geometrical
      inaccuracies and topological errors in the model of cortical surfaces. For
      example, unresolved touching banks of gray matter (GM) in narrow sulci pose a
      particular challenge for an automated algorithm, requiring specific steps for the
      recovery of separating boundaries. We present a method for the automated
      reconstruction of the cortical compartment from MR images. The method is based on
      several partial differential equation (PDE) modelling stages. First, a potential
      field is computed in an electrostatic model with GM posing as an insulating
      dielectric layer surrounding a charged conductive white matter (WM) object.
      Second, geodesic distances from WM along the streamlines of the potential field
      are computed in a Eulerian framework PDE. Third, a digital skeleton surface
      separating GM sulcal banks is derived by finding shocks in the distance field. At
      the last stage, a geometric deformable model based on the level set PDE is used
      to reconstruct the outer cortical surface by advection along the gradient of the
      distance or potential field. The rule preserving the digital topology, and the
      skeleton of the distance field resolving fused adjacent banks in sulci, constrain
      the deformable model evolution. In addition, the deformable model may use the
      distance field as a constraint on thickness of the reconstructed cortical layer.

PMID- 21095751
TI  - Bayesian optimization of perfusion and transit time estimation in PASL-MRI.
AB  - Pulsed Arterial Spin Labeling (PASL) techniques potentially allow the absolute,
      non-invasive quantification of brain perfusion and arterial transit time. This
      can be achieved by fitting a kinetic model to the data acquired at a number of
      inversion time points (TI). The intrinsically low SNR of PASL data, together with
      the uncertainty in the model parameters, can hinder the estimation of the
      parameters of interest. Here, a two-compartment kinetic model is used to estimate
      perfusion and transit time, based on a Maximum a Posteriori (MAP) criterion. A
      priori information concerning the physiological variation of the multiple model
      parameters is used to guide the solution. Monte Carlo simulations are performed
      to compare the accuracy of our proposed Bayesian estimation method with a
      conventional Least Squares (LS) approach, using four different sets of TI points.
      Each set is obtained either with a uniform distribution or an optimal sampling
      strategy designed based on the same MAP criterion. We show that the estimation
      errors are minimized when our proposed Bayesian estimation method is employed in
      combination with an optimal set of sampling points. In conclusion, our results
      indicate that PASL perfusion and transit time measurements would benefit from a
      Bayesian approach for the optimization of both the sampling strategy and the
      estimation algorithm, whereby prior information on the parameters is used.

PMID- 21095752
TI  - Shape modeling of the corpus callosum.
AB  - A novel approach for shape modeling of the corpus callosum (cc) is introduced
      where the contours of the cc are extracted by image/volume segmentation, and a
      Bezier curve is used to connect the vertices of the sampled contours, generating
      a parametric polynomial representation. These polynomials are shown to maintain
      the characteristics of the original cc, thus are suitable for classification of
      populations. The Bernstein polynomials are used in fitting the Bezier curves. The
      coefficients of the Bernstein polynomials are shown to capture the geometric
      features of the cc, and are able to describe deformations. We use these
      coefficients, in conjunction with the Fourier Descriptors and other features, to
      discriminate between autistic and normal brains. The approach is tested on T1
      weighted MRI scans of 16 normal and 22 autistic subjects and shows its ability to
      provide perfect classification, suggesting that the approach is worth
      investigating on a larger population with the hope of providing early
      identification and intervention of autism using neuroimaging.

PMID- 21095753
TI  - Denoising of LSFCM images with compensation for the photoblinking/photobleaching
      effects.
AB  - Fluorescence confocal microscopy images present a low signal to noise ratio and a
      time intensity decay due to the so called photoblinking and photobleaching
      effects. These effects, together with the Poisson multiplicative noise that
      corrupts the images, make long time biological observation processes very
      difficult.

PMID- 21095754
TI  - Local image enhancement for fiducial marker detection in electronic portal images
      of prostate radiotherapy.
AB  - This paper proposes a new method for the automatic contrast enhancement of
      fiducial markers in low-radiation Electronic Portal Images. It is shown that the
      proposed approach significantly enhances the contrast of the fiducial markers and
      produces results where these markers are clearly visible. The main theoretical
      contribution consists in designing an algorithm that enhances the contrast of
      small structures in noisy images; the parameters of this algorithm are not
      empirically selected, but determined via a maximum search over a contrast metric.
      From a practical standpoint, the proposed method has direct applications in the
      current clinical workflow involving manual marker detection. It is also able to
      significantly improve the performances of automatic marker detection reported in
      literature.

PMID- 21095755
TI  - Compton scattered imaging based on the V-line radon transform and its medical
      imaging applications.
AB  - The Radon transform (RT) on straight lines deals as mathematical foundation for
      many tomographic modalities (e.g. Xray scanner, Positron Emission Tomography),
      using only primary radiation. In this paper, we consider a new RT defined on a
      pair of half-lines forming a letter V, arising from the modeling a two
      dimensional emission imaging process by Compton scattered gamma rays. We
      establish its analytic inverse, which is shown to support the feasibility of the
      reconstruction of a two-dimensional image from scattered radiation collected on a
      one-dimensional collimated camera. Moreover, a filtered back-projection inversion
      method is also constructed. Its main advantages are algorithmic efficiency and
      computational rapidity. We present numerical simulations to illustrate the
      working. To sum up, the V-line RT leads not only to a new imaging principle, but
      also to a new concept of detector with high energetic resolution capable to
      collect the scattered radiation.

PMID- 21095756
TI  - Electromagnetic source imaging for sparse cortical activation patterns.
AB  - We propose modifications to the Automatic Relevance Determination (ARD) algorithm
      for solving the EEG/MEG inverse problem when the activation map of the cortex is
      known to be sparse. We propose to include a term to account for the background
      noise activity, i.e. electric activity of sources not in the cortex. Also, we
      prune the results of the ARD algorithm using a Model Selection criterion to get
      sparser results. Simulations with a realistic head model show a very important
      reduction of the number of sources incorrectly detected as active.

PMID- 21095757
TI  - Analysis of trial-by-trial variability in stimulus-evoked neural activity.
AB  - Using standard dimensionality reduction analysis we examined the stimulus-evoked
      neural activity over time and their variability across trials. Consistent with
      earlier results, we found that odor pulses evoked spatio-temporal responses
      distributed throughout an ensemble of simultaneous recorded neurons. Responses
      clustered based on odor identity despite the presence of a relatively small
      amount of trial-by-trial variability. We found that this scatter across trials
      can be reduced using a simple linear projection of the data.

PMID- 21095758
TI  - Psychoacoustic active noise control with ITU-R 468 noise weighting and its sound
      quality analysis.
AB  - Non-uniform frequency response of human hearing system requires conventional
      active noise control (ANC) system to be modified. Psychoacoustic active noise
      control (PANC) system based on filtered-E least-mean-square (FELMS) structure
      aims to improve the noise attenuation performance in terms of hearing perception.
      ITU-R 468 noise weighting reflects human hearing response to random noise. In
      this paper we incorporate ITU-R 468 noise weighting into PANC system. Sound
      quality analysis is conducted for attenuated noise with a predictive pleasantness
      model which combines four psychoacoustic parameters (loudness, sharpness,
      roughness and tonality). Simulation on realistic MRI acoustic noise shows
      improvement of sound quality in the new system.

PMID- 21095759
TI  - Performance enhancement of adaptive Active Noise Control systems for FMRI
      machines.
AB  - Active Noise Control (ANC) of fMRI acoustic noise using the conventional Filtered
      X LMS (FXLMS) approach results in poor cancelation performance and slow
      convergence due to its broadband nature and the need for high order adaptive
      filters. High order adaptive filters are needed to effectively model the long
      acoustic impulse responses. Existing methods to improve the performance of FXLMS
      based broadband ANC systems are either computationally expensive or need
      elaborate implementation. In this paper we show a practical method to enhance the
      performance of FXLMS based algorithms, by deriving a crude estimate of the
      causalWiener filter and initializing the adaptive filter with the estimated
      Wiener filter. We observe that very fast convergence to the global minimum can be
      achieved along with huge gains in the noise cancelation performance. We call this
      method Wiener initialized FXLMS (WI-FXLMS).We show the effectiveness of the
      proposed approach for the active noise control of functional MRI acoustic noise
      and several other realistic noise sources.

PMID- 21095760
TI  - Continuous monitoring of electrodermal activity during epileptic seizures using a
      wearable sensor.
AB  - We present a novel method for monitoring sympathetic nervous system activity
      during epileptic seizures using a wearable sensor measuring electrodermal
      activity (EDA). The wearable sensor enables long-term, continuous EDA recordings
      from patients. Preliminary results from our pilot study suggest that epileptic
      seizures induce a surge in EDA. These changes are greater in generalized tonic
      clonic seizures and reflect a massive sympathetic discharge. This paper offers a
      new approach for investigating the relationship between epileptic seizures and
      autonomic alterations.

PMID- 21095761
TI  - Silicon nanophotonic devices for integrated lab-on-a-chip sensing.
AB  - We present our recent progress in designing nanophotonic devices for integrated
      sensing applications. We focus on Si-based microresonators and on-chip
      spectrometers as the main building blocks to implement compact sensing platforms
      with strong light-matter interaction. The performance of these devices is
      discussed, and their future prospects in realizing low-power low-cost portable
      multi-purpose sensing systems are addressed.

PMID- 21095762
TI  - The deployment of information systems and information technology in field
      hospitals.
AB  - Information systems and related technologies continue to develop and have become
      an integral part of healthcare provision and hospital care in particular. Field
      hospitals typically operate in the most austere and difficult of conditions and
      have yet to fully exploit related technologies. This paper addresses those
      aspects of healthcare informatics, healthcare knowledge management and lean
      healthcare that can be applied to field hospitals, with a view to improving
      patient care. The aim is to provide a vision for the deployment of information
      systems and information technology in field hospitals, using the British Army's
      field hospital as a representative model.

PMID- 21095763
TI  - In a hospital: An electrical safety and information system.
AB  - Literatures in the health areas are reported frequently on accidents caused by
      problems with shock during surgery in both patients as the clinical team. It
      should be noted that most electrical equipment, during use, is often in contact
      with the patient and / or with medical professionals. Therefore, the electric
      shock danger always exists in this environment. To avoid this, some equipment has
      been identified for monitoring IT-system and the use of these normally required
      by standards. The research described in this paper presents an electrical safety
      and information system in a critical environment on the hospital that meets the
      standard. This system has an insulation monitoring device and annunciator, part
      of the IT-system, with unpublished characteristics.

PMID- 21095764
TI  - Development of a personal electronic health record card in the United Kingdom.
AB  - In most emergency situations, health professionals rely on patients to provide
      information about their medical history. However, in some cases patients might
      not be able to communicate this information, and in most countries, including the
      UK an on-line integrated patient record system has not been adopted. Therefore,
      in order to address this issue the ongoing project MyCare Card (MyC(2),
      www.myc2.org) has been established. The aim of this project is to design,
      implement and evaluate a prototype patient held electronic health record card.
      One of the tasks involved in the project was to develop a Graphical User
      Interface (GUI) software, which provides access to the data stored on the card.
      The requirements for this software had to be established via questionnaire
      surveys and end user evaluations, conducted simultaneously with the software
      development. This paper is addressing development of the MyCare Card GUI
      software. It also overviews the hardware and open-source software solutions
      selected for the MyCare Card implementation.

PMID- 21095765
TI  - Semantic similarity measure in biomedical domain leverage web search engine.
AB  - Semantic similarity measure plays an essential role in Information Retrieval and
      Natural Language Processing. In this paper we propose a page-count-based semantic
      similarity measure and apply it in biomedical domains. Previous researches in
      semantic web related applications have deployed various semantic similarity
      measures. Despite the usefulness of the measurements in those applications,
      measuring semantic similarity between two terms remains a challenge task. The
      proposed method exploits page counts returned by the Web Search Engine. We define
      various similarity scores for two given terms P and Q, using the page counts for
      querying P, Q and P AND Q. Moreover, we propose a novel approach to compute
      semantic similarity using lexico-syntactic patterns with page counts. These
      different similarity scores are integrated adapting support vector machines, to
      leverage the robustness of semantic similarity measures. Experimental results on
      two datasets achieve correlation coefficients of 0.798 on the dataset provided by
      A. Hliaoutakis, 0.705 on the dataset provide by T. Pedersen with physician scores
      and 0.496 on the dataset provided by T. Pedersen et al. with expert scores.

PMID- 21095766
TI  - A new XML-aware compression technique for improving performance of healthcare
      information systems over hospital networks.
AB  - Most organizations exchange, collect, store and process data over the Internet.
      Many hospital networks deploy Web services to send and receive patient
      information. SOAP (Simple Object Access Protocol) is the most usable
      communication protocol for Web services. XML is the standard encoding language of
      SOAP messages. However, the major drawback of XML messages is the high network
      traffic caused by large overheads. In this paper, two XML-aware compressors are
      suggested to compress patient messages stemming from any data transactions
      between Web clients and servers. The proposed compression techniques are based on
      the XML structure concepts and use both fixed-length and Huffman encoding methods
      for translating the XML message tree. Experiments show that they outperform all
      the conventional compression methods and can save tremendous amount of network
      bandwidth.

PMID- 21095767
TI  - Estimation of alertness levels with changes in decibel scale wavelength of EEG
      during dual-task simulation of auditory sonar target detection.
AB  - Changes in alertness levels can have dire consequences for people operating and
      controlling motorized equipment. Past research studies have shown the
      relationship of Electroencephalogram (EEG) with alertness of the person. This
      research reports the fractal analysis of EEG and estimation of the alertness
      levels of the individual based on the changes in the maximum fractal length (MFL)
      of EEG. The results indicate that MFL of only 2 channels of EEG can be used to
      identify the loss of alertness of the individual with mean (inverse) correlation
      coefficient = 0.82. This study has also reported that using the changes in MFL of
      EEG, the changes in alertness level of a person was estimated with a mean
      correlation coefficient = 0.69.

PMID- 21095768
TI  - Behavioural microsleeps in normally-rested people.
AB  - Sleep-deprived people, or those performing extended monotonous tasks, frequently
      have brief episodes when performance is suspended and they appear to fall asleep
      momentarily - behavioural microsleeps (BMs). As BM rates are highly variable
      between normally-rested people, this study aimed to determine whether there is a
      relationship between propensity for BMs and measures of sleep. Subjects undertook
      a continuous 50-min 2-D tracking task and BMs were identified with high temporal
      accuracy based on simultaneous analysis of visuomotor response, tracking speed,
      tracking error, vertical electrooculogram, and eye-video. BM rates and durations
      were correlated with measures of sleep (i.e., wrist actigraphy, Epworth
      Sleepiness Scale, Pittsburgh Sleep Quality Index, and Horne-Ostberg Morning
      Eveningness Questionnaire). BMs occurred frequently during the task but rates
      were highly variable between participants (mean 79.1/h +/- 66.2, range 0-226/h).
      There were correlations between ESS score and BM rate and duration. However, BMs
      were not related to other sleep measures. Thus, there is a very large variability
      in BM propensity in normally-rested subjects which cannot be explained by
      variation in sleep duration, quality, or efficiency. Propensity to fall asleep in
      situations in which sustained performance is required may be a trait
      characteristic in normally-rested people.

PMID- 21095769
TI  - The relationship between behavioural microsleeps, visuomotor performance and EEG
      theta.
AB  - Visuomotor performance and responsiveness deteriorates with time-on-task due to
      drowsiness and increased propensity to sleep. Frequent episodes of behavioural
      microsleep (BM) are also common during extended and monotonous tasks. In this
      study, simultaneous recording of EEG, eye-video, and continuous visuomotor
      response is used to investigate visuomotor performance and EEG activity during
      tonic drowsiness and phasic BMs. The data were collected from 20 healthy
      volunteers while they performed a continuous 2-D pursuit tracking task for 50
      min. We identified episodes of BMs by expert visual rating of eye-video and
      visuomotor response using a set of pre-defined criteria. Visuomotor performance
      and EEG activity were correlated with and without BM events. A moderate
      correlation was observed between visuomotor error and theta activity in EEG at a
      posterior channel (Pz) before the removal of BMs. However, when BMs were removed
      from the data, the correlation dropped in most subjects. Furthermore, most of the
      large fluctuations in performance observed during the visuomotor task disappeared
      after the removal of BMs. This suggests that episodic behaviours such as BMs
      contribute substantially to fluctuations in performance and to EEG theta activity
      during an extended task, and that they should be taken into account when studying
      tonic drowsiness.

PMID- 21095770
TI  - Evaluation of PERCLOS based current fatigue monitoring technologies.
AB  - In an overnight driving simulation study three commercially available devices of
      fatigue monitoring technologies (FMT) were applied to test their accuracy. 16
      volunteers performed driving tasks during eight sessions (40 min each) separated
      by 15 minutes breaks. The main output variable of FMT devices, which is the
      percentage of eye closure (PERCLOS), the driving performance (standard deviation
      of lateral position in lane, SDL), the electroencephalogram (EEG) and
      electrooculogram (EOG) were recorded during driving. In addition, the subjective
      self-rated Karolinska sleepiness scale (KSS) was assessed every 2 min. As
      expected, Pearson product-moment correlation coefficient (PMCC) yielded
      significant linear dependence between KSS and PERCLOS as well as between SDL and
      PERCLOS. However, if PMCC was estimated within smaller data segments (3 min) as
      well as without averaging across subjects then strongly decreased correlation
      coefficients resulted. To further validate PERCLOS at higher temporal resolution
      its ability to discriminate between mild and strong fatigue was investigated and
      compared to the results of the same analysis for EEG/EOG. Spectral-domain
      features of both types of signals were classified using Support-Vector Machines
      (SVM). Results suggest that EEG/EOG indicate driver fatigue much better than
      PERCLOS. Therefore, current FMT devices perform acceptably if temporal resolution
      is low (> 20 min). But, even under laboratory conditions large errors have to be
      expected if fatigue is estimated on an individual level and with high temporal
      resolution.

PMID- 21095771
TI  - Improving classification rates for use in fatigue countermeasure devices using
      brain activity.
AB  - Fatigue can be defined as a state that involves psychological and physical
      tiredness with a range of symptoms such as tired eyes, yawning and increased
      blink rate. It has major implications for work place and road safety as well as a
      negative symptom of many acute and chronic illnesses. As such there has been
      considerable research dedicated to systems or algorithms that can be used to
      detect and monitor the onset of fatigue. This paper examines using
      electroencephalography (EEG) signals to classify fatigue and alert states as a
      function of subjective self-report, driving performance and physiological
      symptoms. The results show that EEG classification network for fatigue improved
      from 75% to 80% when these factors are applied, especially when the data is
      grouped by subjective self-report of fatigue with classification accuracy
      improving to 84.5%.

PMID- 21095772
TI  - Wireless physiological monitoring and ocular tracking: 3D calibration in a fully
      immersive virtual health care environment.
AB  - Wireless physiological/neurological monitoring in virtual reality (VR) offers a
      unique opportunity for unobtrusively quantifying human responses to precisely
      controlled and readily modulated VR representations of health care environments.
      Here we present such a wireless, light-weight head-mounted system for measuring
      electrooculogram (EOG) and electroencephalogram (EEG) activity in human subjects
      interacting with and navigating in the Calit2 StarCAVE, a five-sided immersive 3
      D visualization VR environment. The system can be easily expanded to include
      other measurements, such as cardiac activity and galvanic skin responses. We
      demonstrate the capacity of the system to track focus of gaze in 3-D and report a
      novel calibration procedure for estimating eye movements from responses to the
      presentation of a set of dynamic visual cues in the StarCAVE. We discuss cyber
      and clinical applications that include a 3-D cursor for visual navigation in VR
      interactive environments, and the monitoring of neurological and ocular
      dysfunction in vision/attention disorders.

PMID- 21095773
TI  - Development of body weight support gait training system using antagonistic bi
      articular muscle model.
AB  - The purpose of this study is to develop a body weight support gait training
      system for stroke and spinal cord injury. This system consists of a powered
      orthosis, treadmill and equipment of body weight support. Attachment of the
      powered orthosis is able to fit subject who has difference of body size. This
      powered orthosis is driven by pneumatic McKibben actuator. Actuators are arranged
      as pair of antagonistic bi-articular muscle model and two pairs of antagonistic
      mono-articular muscle model like human musculoskeletal system. Part of the
      equipment of body weight support suspend subject by wire harness, and body weight
      of subject is supported continuously by counter weight. The powered orthosis is
      attached equipment of body weight support by parallel linkage, and movement of
      the powered orthosis is limited at sagittal plane. Weight of the powered orthosis
      is compensated by parallel linkage with gas-spring. In this study, we developed
      system that has orthosis powered by pneumatic McKibben actuators and equipment of
      body weight support. We report detail of our developed body weight support gait
      training system.

PMID- 21095774
TI  - Bio cooperative robotic platform for motor function recovery of the upper limb
      after stroke.
AB  - Biocooperative augmented robots, can enhance rehabilitation therapies by giving
      the correct assistance at the correct time. Since different patients may benefit
      from different amounts of assistance or resistance at a given time, predicting
      when a person enters in an undesired psychophysiological state can provide an
      intelligent system with important information about when to initiate interaction.
      This paper presents a subject centered approach method that includes the human
      into the loop by using physiological feedback techniques. This allows the robot
      to adapt to several different patients and maintain the therapy as intensive as
      possible without compromising patients health or letting the individual get
      stressed which would result in a decay of the overall performance.

PMID- 21095775
TI  - A telepresence robotic system operated with a P300-based brain-computer
      interface: initial tests with ALS patients.
AB  - Brain-computer interfaces (BCIs) open a new valuable communication channel for
      people with severe neurological or motor degenerative diseases, such as ALS
      patients. On the other hand, the ability to teleoperate robots in a remote
      scenario provides a physical entity embodied in a real environment ready to
      perceive, explore, and interact. The combination of both functionalities provides
      a system with benefits for ALS patients in the context of neurorehabilitation or
      maintainment of the neural activity. This paper reports a BCI telepresence system
      which offers navigation, exploration and bidirectional communication, only
      controlled by brain activity; and an initial study of applicability with ALS
      patients. The results show the feasibility of this technology in real patients.

PMID- 21095776
TI  - Efficacy of robotic rehabilitation of ankle impairments in children with cerebral
      palsy.
AB  - The current study introduces a novel rehabilitation robot for treatment of
      impaired ankle in children with cerebral palsy (CP). The treatment consisted of
      passive stretching under intelligent control and active movement training with
      motivating game-playing using the portable robot. After 18 sessions of training
      (3 sessions/week for 6 weeks), we found significant improvement in 12 children
      with CP in terms of improved passive and active ranges of motion, selective motor
      control and mobility functions. The positive outcomes of this study along with
      the improvements in motor control and functional activities suggest that robotic
      rehabilitation provides a useful and convenient option of treatment in clinic or
      patient home for more accessible and frequent rehabilitation.

PMID- 21095777
TI  - Hand function recovery in chronic stroke with HEXORR robotic training: A case
      series.
AB  - After a stroke, many survivors have impaired motor function. Robotic
      rehabilitation techniques have emerged to provide a repetitive, activity-based
      therapy at potentially lower cost than conventional methods. Many patients
      exhibit intrinsic resistance to hand extension in the form of spasticity and/or
      hypertonia. We have developed a therapy program using the Hand Exoskeleton
      Rehabilitation Robot (HEXORR) that is capable of compensating for tone to assist
      patients in opening the paretic hand. The system can move the user's hand, assist
      movement, allow free movement, or restrict movement to allow static force
      production. These options combine with an interactive virtual reality game to
      enhance user motivation. Four chronic stroke subjects received 18 sessions of
      robot therapy as well as pre and post evaluation sessions. All subjects showed at
      least modest gains in active finger range of motion (ROM) measured in the robot,
      and all but one subject had gains in active thumb ROM. Most of these gains
      carried over to ROM gains outside of the robot. The clinical measures (Fugl
      Meyer, Box-and-Blocks) showed clear improvements in two subjects and mixed
      results in two subjects. Overall, the robot therapy was well received by subjects
      and shows promising results. We conclude HEXORR therapy is best suited for
      patients with mild-moderate tone and at least minimal extension.

PMID- 21095778
TI  - Gravity compensation of an upper extremity exoskeleton.
AB  - This paper presents a new gravity compensation method for an upper extremity
      exoskeleton mounted on a wheel chair. This new device is dedicated to regular and
      efficient rehabilitation training for post-stroke and injured people without the
      continuous presence of a therapist. The exoskeleton is a wearable robotic device
      attached to the human arm. The user provides information signals to the
      controller by means of the force sensors around the wrist and the arm, and the
      robot controller generates the appropriate control signals for different training
      strategies and paradigms. This upper extremity exoskeleton covers four basic
      degrees of freedom of the shoulder and the elbow joints with three additional
      adaptability degrees of freedom in order to match the arm anatomy of different
      users. For comfortable and efficient rehabilitation, a new heuristic method have
      been studied and applied on our prototype in order to calculate the gravity
      compensation model without the need to identify the mass parameters. It is based
      on the geometric model of the robot and accurate torque measurements of the
      prototype's actuators in a set of specifically chosen joint positions. The weight
      effect has been successfully compensated so that the user can move his arm freely
      while wearing the exoskeleton without feeling its mass.

PMID- 21095779
TI  - Neuro-mechanical control using differential stochastic operators.
AB  - In order to understand how populations of neurons control movement, several
      phenomena beyond the realm of classical control theory must be addressed. These
      include the effect of variability in control due to stochastic firing, the effect
      of large partially unlabeled cooperative controllers, the effect of bandlimited
      control due to finite neural resources, and the effect of variation in the number
      of available neurons. I propose to use differential stochastic operators to model
      the time-varying effect of multiple stochastic controllers. Integration of these
      operators yields the time evolution of the probability density of the state. The
      main result is that since these operators are linear, the combined dynamic effect
      of populations of neurons can be described by linear combinations of the
      operators for individual neurons. This permits prediction of the effect of
      changes in the firing pattern of neurons, and control can be achieved by changing
      the firing rates of different neurons in a population. The mathematical
      formulation permits prediction of uncertainty and variability in control, and it
      also permits prediction of the effect of increase (growth) or decrease (injury)
      in the number of neurons on the accuracy and stability of control. The theory
      provides a strong mathematical link between the behavior of individual neurons
      and populations of neurons, and the dynamic behavior of neuro-mechanical systems.

PMID- 21095780
TI  - Modeling the biomechanical constraints on the feedforward control of endpoint
      stiffness.
AB  - Appropriate regulation of human arm mechanics is essential for completing the
      diverse range of tasks we accomplish each day. The steady state mechanical
      properties of the arm most relevant for postural tasks can be characterized by
      endpoint stiffness, the static forces generated by a limb in response to external
      perturbations of posture. Endpoint stiffness is directional, resisting
      perturbations in certain directions more than others. It has been shown that
      humans can voluntarily control the orientation of the maximum stiffness to meet
      specific task requirements, although the limits on this control are poorly
      understood. Both neural and biomechanical factors may limit endpoint stiffness
      control. The purpose of this work was to quantify the biomechanical constraints
      limiting the control of stiffness orientation. A realistic musculoskeletal model
      of the human arm coupled with a model of muscle stiffness was used to explore the
      range of endpoint stiffness orientations that could be achieved with changes in
      the feedforward control of muscle activation. We found that this range is
      constrained by the biomechanics of the neuromuscular system, and by the
      requirements of the specific task being performed by the subject. These
      constraints and the sensitivity to experimental conditions may account for some
      of the discrepancies in the literature regarding the ability to control endpoint
      stiffness orientation.

PMID- 21095781
TI  - Understanding complex muscles in the rat hindlimb: Activations and actions.
AB  - We present research examining the function of complex muscles in the rat
      hindlimb. Two related sets of experiments are described. In the first, we examine
      the degree of specificity in spinal pattern generators, assessing whether the
      pattern generators at birth are capable of differentially activating
      intramuscular subdivisions in the complex hindlimb muscle biceps femoris. In the
      second, we describe a novel approach for creating a musculoskeletal model to
      capture the mechanical actions of individual muscles and evaluate its ability to
      capture the action of both simple and complex muscles in the rat hindlimb.

PMID- 21095782
TI  - Towards a neuronal network controller for vertical jumping from different initial
      squat depths.
AB  - In this study, a forward dynamic simulation model of the human musculoskeletal
      system was used to explore various strategies of generating muscle stimulation
      patterns for vertical squat jumping. It was shown that a simple mapping from
      joint angles to muscle stimulation onsets yielded successful control, albeit not
      optimal control, for jumps from different initial squat depths. Furthermore, it
      was shown that this mapping could be implemented in a straightforward way in a
      simple network of Hodgkin-Huxley type neurons.

PMID- 21095783
TI  - Optimality in neuromuscular systems.
AB  - We provide an overview of optimal control methods to nonlinear neuromuscular
      systems and discuss their limitations. Moreover we extend current optimal control
      methods to their application to neuromuscular models with realistically numerous
      musculotendons; as most prior work is limited to torque-driven systems. Recent
      work on computational motor control has explored the used of control theory and
      estimation as a conceptual tool to understand the underlying computational
      principles of neuromuscular systems. After all, successful biological systems
      regularly meet conditions for stability, robustness and performance for multiple
      classes of complex tasks. Among a variety of proposed control theory frameworks
      to explain this, stochastic optimal control has become a dominant framework to
      the point of being a standard computational technique to reproduce kinematic
      trajectories of reaching movements (see [12]) In particular, we demonstrate the
      application of optimal control to a neuromuscular model of the index finger with
      all seven musculotendons producing a tapping task. Our simulations include 1) a
      muscle model that includes force- length and force-velocity characteristics; 2)
      an anatomically plausible biomechanical model of the index finger that includes a
      tendinous network for the extensor mechanism and 3) a contact model that is based
      on a nonlinear spring-damper attached at the end effector of the index finger. We
      demonstrate that it is feasible to apply optimal control to systems with
      realistically large state vectors and conclude that, while optimal control is an
      adequate formalism to create computational models of neuro-musculoskeletal
      systems, there remain important challenges and limitations that need to be
      considered and overcome such as contact transitions, curse of dimensionality, and
      constraints on states and controls.

PMID- 21095784
TI  - A predictive model of the isometric force response of the locust extensor muscle.
AB  - A predictive model that can be used to estimate the isometric force response of
      the locust hind leg extensor muscle is presented. The model consists of two first
      order coupled differential equations. The first of these equations is linear and
      relates an input pulse train to the calcium concentration in muscle filaments.
      The second is non-linear and relates the calcium concentration to muscle force.
      Experimental data was collected by stimulating the extensor muscle and measuring
      the force generated at the tibia. Model parameters were estimated by minimising
      the error between the modelled and actual force response in a set of training
      data. These parameters were then used to predict the isometric response when the
      neural activity recorded during a kick was used as an input to the model. The
      model was found to accurately predict the isometric force response of the locust
      hind leg extensor muscle.

PMID- 21095785
TI  - Mapping visual stimuli to perceptual decisions via sparse decoding of mesoscopic
      neural activity.
AB  - In this talk I will describe our work investigating sparse decoding of neural
      activity, given a realistic mapping of the visual scene to neuronal spike trains
      generated by a model of primary visual cortex (V1). We use a linear decoder which
      imposes sparsity via an L1 norm. The decoder can be viewed as a decoding neuron
      (linear summation followed by a sigmoidal nonlinearity) in which there are
      relatively few non-zero synaptic weights. We find: (1) the best decoding
      performance is for a representation that is sparse in both space and time, (2)
      decoding of a temporal code results in better performance than a rate code and is
      also a better fit to the psychophysical data, (3) the number of neurons required
      for decoding increases monotonically as signal-to-noise in the stimulus
      decreases, with as little as 1% of the neurons required for decoding at the
      highest signal-to-noise levels, and (4) sparse decoding results in a more
      accurate decoding of the stimulus and is a better fit to psychophysical
      performance than a distributed decoding, for example one imposed by an L2 norm.
      We conclude that sparse coding is well-justified from a decoding perspective in
      that it results in a minimum number of neurons and maximum accuracy when sparse
      representations can be decoded from the neural dynamics.

PMID- 21095786
TI  - Assessment of lower extremity motor adaptation via an extension of the force
      field adaptation paradigm.
AB  - Lower extremity rehabilitation has seen recent increased interest. New tools are
      available to improve gait retraining in both adults and children. However, it
      remains difficult to determine optimal ways to plan interventions due to
      difficulties in continuously monitoring outcomes in patients undergoing
      rehabilitation. In this paper, we introduce an extension of the Force Field
      Adaptation Paradigm, used to quantitatively assess upper extremity motor
      adaptation, to the lower extremity. The algorithm is implemented on the Lokomat
      lower extremity gait orthosis and utilized to assess short-term motor adaptation.
      Establishing an understanding of how healthy adults' motor systems adapt to
      external perturbations will be important to understanding how the adaptive
      mechanisms involved in gait are altered by disease.

PMID- 21095787
TI  - Prefrontal cortex deletion affects the dopaminergic neural firing complexity in
      nicotine-treated ventral tegmental area.
AB  - Nicotine, an addictive substance in cigarette, triggers glutamatergic synaptic
      plasticity on ventral tegmental area (VTA) dopamine (DA) neurons. The functional
      coupling between prefrontal cortex (PFC) and VTA has been demonstrated, but
      little is known how PFC mediates nicotinic modulation in VTA DA neurons. In this
      study, we tested the hypothesis that systemic exposure to nicotine significantly
      increases the VTA DA neuron's complexity of firing. The complexity of the neural
      firing of VTA DA neurons was significantly increased in PFC intact subjects, as
      determined using the advanced nonlinear dynamic method based on the Lempel-Ziv
      estimator. To further understand the functional coupling between PFC and VTA, we
      used LZ complexity method to estimate the complexity of firing of PFC transected
      subjects. Interestingly, without the input from PFC, the change in complexity
      estimated from VTA for PFC transected subjects is not significant. The results
      suggest PFC plays an important role in mediating VTA activity and that the LZ
      complexity method is a useful tool for the characterization of the dynamical
      changes in VTA DA neurons firing activities.

PMID- 21095788
TI  - A domain model of a clinical reading center - Design and implementation.
AB  - In clinical trials huge amounts of raw data are generated. Often these data are
      submitted to reading centers for being analyzed by experts of that particular
      type of examination. Although the installment of a reading center can raise the
      overall quality, they also introduce additional complexity to the management and
      conduction of a clinical trial. Software can help to handle this complexity.
      Domain-driven-design is one concept to tackle software development in such
      complex domains. Here we present our domain model for a clinical reading center,
      as well as its actual implementation utilizing the Nuxeo enterprise content
      management system.

PMID- 21095789
TI  - TongueWise: Tongue-computer interface software for people with tetraplegia.
AB  - Many computer interfaces and assistive devices for people with motor disabilities
      limit the input dimensionality from user to system, in many cases leading to
      single switch interfaces where the user can only press one button. This can,
      either limit the level of direct access to the functionalities of the operating
      system, or slow down speed of interaction. In this paper we present TongueWise: a
      software developed for a tongue computer interface that can be activated with the
      tip of the tongue and that provides direct input that covers most of the standard
      keyboard and mouse commands.

PMID- 21095790
TI  - Smartphone based face recognition tool for the blind.
AB  - The inability to identify people during group meetings is a disadvantage for
      blind people in many professional and educational situations. To explore the
      efficacy of face recognition using smartphones in these settings, we have
      prototyped and tested a face recognition tool for blind users. The tool utilizes
      Smartphone technology in conjunction with a wireless network to provide audio
      feedback of the people in front of the blind user. Testing indicated that the
      face recognition technology can tolerate up to a 40 degree angle between the
      direction a person is looking and the camera's axis and a 96% success rate with
      no false positives. Future work will be done to further develop the technology
      for local face recognition on the smartphone in addition to remote server based
      face recognition.

PMID- 21095791
TI  - User inspection of National Taiwan University Hospital's telehealth care
      information system.
AB  - The telehealth care system has been important in the healthcare world for several
      decades; however, Taiwan only began work on telehealth care this past year. This
      paper outlines the effectiveness of the telehealth care system developed by the
      National Taiwan University Hospital (NTUH). The usability of the integrated
      telehealth care system was analyzed through of heuristic evaluation and its
      usefulness. By using the heuristic evaluation form as developed by Nielsen, it is
      possible to examine the telehealth care system from the user's perspective. In
      addition, in assessing the usefulness through lists of criteria, system
      developers can determine the pros and the cons of the database. Ultimately, the
      heuristic evaluation revealed several violations on the system, but are not
      prohibitive to the development of such as system. Similarly, evaluation of the
      usefulness comes out positive; despite the fact that the suggested changes
      proposed by the users can be said are the main weaknesses of the system. With
      some improvements, the telehealth care system can be used efficiently in NTUH's
      healthcare system.

PMID- 21095792
TI  - The effect of wavelet-based filtering and data set length on the fractal scaling
      of cardiorespiratory variability.
AB  - The effect of filtering and data set length on the accuracy of the quantification
      of fractal characteristics of cardiorespiratory activity remains unclear. Breath
      to-breath interval (BBI) and heartbeat-to-heartbeat interval (RRI) were recorded
      from 8 healthy human subjects during a quiet seated posture. Movement artifact
      was filtered from the raw respiratory data using a simple low-pass (LP) or a
      wavelet-based (WB) filter. The RRI data was segmented into three sets of 256,
      512, and 1024 sequential data points. BBI and RRI fractal scaling was quantified
      using detrended fluctuation analysis and a wavelet-based estimation of fractal
      dimension. No significant difference in the calculation of fractal behavior of
      BBI was identified after using a LP or a WB filter. Furthermore, there was no
      significant difference in fractal measurements among the different RRI data set
      lengths. In conclusion, filtering of physiologic data with standard LP or WB
      techniques or data set length, between 256 and 1024 sequential points, does not
      significantly affect the calculation of fractal behavior.

PMID- 21095793
TI  - Arterial pressure and diameter waveforms analysis by means of wavelet transform:
      application to artery de-endothelization.
AB  - In this present paper, we showed that wavelet analysis (WA) has the potential for
      extracting specific features from measured arterial diameter and pressure
      waveforms. The fifth detail of the Daubechies 4 (Db4) wavelet appears to be the
      most appropriate level for application, in order to analyze artery waveforms and
      was used to characterized arterial de-endothelization (DE). Raises in smooth
      muscle tone induced by (DE) tended to increase arterial stiffness and therefore
      that WA details embed the information of the diameter and pressure pulse that
      contains the signature of effects of wave travel and reflection affected by
      arterial stiffness.

PMID- 21095794
TI  - Variable optimisation of medical image data by the learning Bayesian Network
      reasoning.
AB  - The method proposed here uses Bayesian non-linear classifier to select optimal
      subset of attributes to avoid redundant variables and reduce data uncertainty in
      the classification process often used in medical diagnosis. The method also
      exploits the structural reasoning ability of Bayesian Networks (BN) to optimize
      large number of attributes to prevent overfitting, meanwhile it maintains the
      high classification accuracy. This process simplifies the complex data analyses
      and may lead to a cost reduction in clinical data acquisition process.

PMID- 21095795
TI  - An asynchronous BMI system for online single-trial detection of movement
      intention.
AB  - This paper presents an approach for an asynchronous BMI proposed as a switching
      part of a tremor suppression system developed for real-time continuous
      conditions. The main purpose of this BMI-switch is to anticipate the execution of
      self-initiated movements performed after relatively long periods of inactivity.
      The performance indicators used for the detector validation are specially suited
      for the continuous characteristic of the paradigm used and it is demonstrated
      that our ERD-based bayesian classifier solution is a reliable option, detecting a
      high rate of positive cases and generating very few false positives during long
      intervals of inactivity. The subjects analyzed for our detector validation were
      patients with neurological tremor caused by different pathologies in order to
      assure the adaptability of our system.

PMID- 21095796
TI  - Heart murmur classification with feature selection.
AB  - Heart sounds entail crucial heart function information. In conditions of heart
      abnormalities, such as valve dysfunctions and rapid blood flow, additional sounds
      are heard in regular heart sounds, which can be employed in pathology diagnosis.
      These additional sounds, or so-called murmurs, show different characteristics
      with respect to cardiovascular heart diseases, namely heart valve disorders. In
      this paper, we present a method of heart murmur classification composed by three
      basic steps: feature extraction, feature selection, and classification using a
      nonlinear classifier. A new set of 17 features extracted in the time, frequency
      and in the state space domain is suggested. The features applied for murmur
      classification are selected using the floating sequential forward method (SFFS).
      Using this approach, the original set of 17 features is reduced to 10 features.
      The classification results achieved using the proposed method are compared on a
      common database with the classification results obtained using the feature sets
      proposed in two well-known state of the art methods for murmur classification.
      The achieved results suggest that the proposed method achieves slightly better
      results using a smaller feature set.

PMID- 21095797
TI  - Oscillations in the evaluation of fractal dimension of RR intervals time series.
AB  - Previously, we have reported the presence of oscillations in the graphs we have
      used to evaluate the Higuchi's fractal dimension in RR intervals time series of
      congestive heart failure (CHF) patients in the sleep phase but these oscillations
      hardly appear in all the six hours of the awake phase. In this paper we report
      the same analysis for heart rate time series for different groups of healthy
      subjects; we are looking for the presence of this kind of oscillations in other
      situations. We analyzed all the time series in the Exaggerated Heart Rate
      Oscillations database of Physionet during two meditation techniques: volunteers
      with spontaneous breathing, subjects in meditation, volunteers in a metronomic
      breathing group and elite athletes. We have found oscillations in the graphs of
      the Higuchi's fractal dimension in the heart rate time series of subjects in
      meditation and metronomic breathing and this fact coincides with previous
      reported results.

PMID- 21095798
TI  - Improving discriminality in heart rate variability analysis using simple artifact
      and trend removal preprocessors.
AB  - Heart Rate variability (HRV) is important in characterizing heart functions.
      However, artifacts and trends are regularly observed to contaminate the HRV
      sequences. This study proposes a simple and effective preprocessor for the
      removal of artifacts and trend in the HRV sequences. A thresholding filter is
      applied to remove artifacts to maintain the HRV sequences in a reasonable range.
      A wavelet filter proceeds to remove the ultra and very low frequency components
      determined as trends. As a consequence, more reliable low frequency (LF) and high
      frequency (HF) components can be calculated, which are believed to be close
      related to the autonomic nervous system (ANS) regulation of the heart. The result
      demonstrates that features calculated from the power spectral density of the
      preprocessed HRV are more separable in feature space when compared with that from
      the original HRV. A simple KNN classifier is employed to justify the effects of
      this preprocessor in differentiating congestive heart failure (CHF) from the
      normal sinus rhythms (NSR). Using five features calculated from LF and HF, the
      performance of the KNN classifier shows significant improvement after applying
      the preprocessors. When compared with the other studies published in the
      literature, the proposed method outperforms them in CHF recognition with a much
      simpler scheme.

PMID- 21095799
TI  - Computer-aided auscultation to diagnose Renal Artery Stenosis.
AB  - Renal Artery Stenosis (RAS) is the most common cause of secondary hypertension,
      and early diagnosis is important since correct and timely treatment may cure
      hypertension and prevent loss of renal function. This study investigates a new
      approach to diagnosing renal artery stenosis by computer analysis of the
      phonogram recorded with an electronic stethoscope. Phonograms recorded from five
      positions over the renal arteries were obtained, three from patients with
      confirmed RAS and 15 from healthy subjects. Two features describing the power
      ratios between the systolic and diastolic periods in two different frequency
      bands were extracted. It was possible to discriminate all three RAS subjects from
      the healthy subjects in the frequency band 0.4-1.1 kHz. However, the number of
      subjects is insufficient to draw statistically significant conclusions about the
      performance of the system.

PMID- 21095800
TI  - PPG delineator for real-time ubiquitous applications.
AB  - This paper presents real-time signal processing algorithm for detection of onsets
      and peaks in Photoplethysmogram (PPG) waveform. Algorithm relies on the analysis
      of amplitude, slope and inter-beat intervals. The presented algorithm consists of
      four stages for characterizing PPG waveform. Preprocessing stage involves
      transformation of PPG since the original waveform is less impulsive and robust.
      In second stage, algorithm seeks for valid pulse detection in transformed signal
      complying with the amplitude threshold and inter-beat interval. On detection of
      valid pulses, algorithm then searches backward and forward in transformed signal
      for the detection of peaks and onsets. Further the detection parameters are made
      adaptive to comply with varying beat morphologies and fluctuations in baseline.
      All signal processing steps and decision logics are implemented with low
      computational complexity to make it applicable for compact ubiquitous health
      monitoring devices. On evaluation with our database, the algorithm achieved
      sensitivity of 96.89% and positive predictivity of 94.55% within an acceptance
      level of 12 ms.

PMID- 21095801
TI  - Rechargeable wireless EMG sensor for prosthetic control.
AB  - Surface electrodes in modern myoelectric prosthetics are often embedded in the
      prosthesis socket and make contact with the skin. These electrodes detect and
      amplify muscle action potentials from voluntary contractions of the muscle in the
      residual limb and are used to control the prosthetic's movement and function.
      There are a number of performance-related deficiencies associated with external
      electrodes including the maintenance of sufficient electromyogram (EMG) signal
      amplitude, extraneous noise acquisition, and proper electrode interface
      maintenance that are expected to be improved or eliminated using the proposed
      implanted sensors. This research seeks to investigate the design components for
      replacing external electrodes with fully-implantable myoelectric sensors that
      include a wireless interface to the prosthetic limbs. This implanted technology
      will allow prosthetic limb manufacturers to provide products with increased
      performance, capability, and patient-comfort. The EMG signals from the
      intramuscular recording electrode are amplified and wirelessly transmitted to a
      receiver in the prosthetic limb. Power to the implant is maintained using a
      rechargeable battery and an inductive energy transfer link from the prosthetic. A
      full experimental system was developed to demonstrate that a wireless
      biopotential sensor can be designed that meets the requirements of size, power,
      and performance for implantation.

PMID- 21095802
TI  - The mean value of the descriptors of the pathological events recorded on the
      polysomnogram as a support tool in the diagnosis of SAHS.
AB  - Commercial polysomnographs used in the test to diagnose Sleep Apnea-Hypopnea
      Syndrome (SAHS) usually generate a report summarizing the test. This report helps
      clinicians in the task of diagnosing the patient. Some of the information
      presented in these reports has been carefully studied and standardized -for
      example, the apnea-hypopnea index. Therefore, there are clear guidelines on how
      to interpret it. However, these reports usually contain other information that
      has not been carefully studied and for which no precise guidelines on how to
      interpret it exist. Examples include the mean values of certain descriptors of
      the pathological events that have occurred during the patient's sleep, such as
      the mean duration of apneas, hypopneas and desaturations, the mean of the minimum
      blood oxyhemoglobin saturation value reached in each desaturation, ecetera. The
      goals of this paper are to study whether this information is useful in the
      diagnosis of SAHS and to try to provide some insight on how to interpret it. To
      this end, we have analyzed the descriptors generated from 97 patients who
      underwent the polysomnographic test, comparing the ones arising from SAHS
      patients with the ones arising from healthy patients.

PMID- 21095803
TI  - Comparison of two commercial patellofemoral prostheses by means of computational
      modeling.
AB  - There are many patellofemoral prostheses designs available for patellofemoral
      resurfacing, but few studies provide results objectively comparing these designs.
      In this study two designs are compared on the basis of patella kinematics and
      patellofemoral kinetics by means of a computational technique. Results indicated
      that the patellae displaced laterally after trochlear engagement, while tilt
      patterns were irregular between volunteers. Patellofemoral contact loads
      increased with knee flexion, whereas medial patellofemoral tension diminished.
      The results from three volunteer-specific models showed that Prosthesis B would
      reproduce similar patella kinematics and patellofemoral kinetics to the baseline
      models. The computational technique provided a means by which prostheses designs
      could be compared with similar input and boundary values.

PMID- 21095804
TI  - Force feedback in limb lengthening.
AB  - A new variable-rate distraction system using a motorized distractor driven by
      feedback from the distraction force was designed. The distractor was mounted on a
      unilateral fixator and attached to the tibiae of 6 sheep that underwent
      distraction osteogenesis. The sheep were divided equally into 3 groups. In group
      1, the forces were recorded but were not used to drive the lengthening rate. In
      group 2, force feedback was used and the desired distraction force level was set
      to 300 N and the initial rate was 1 mm/day. Group 3 also underwent force feedback
      with the desired force limit at 300 N, but the rate change was initiated earlier,
      at 200 N. The distraction force was recorded at 15 second intervals throughout
      the distraction phase and stored onboard the distractor.

PMID- 21095805
TI  - Contact stresses in a patient-specific unicompartmental knee replacement.
AB  - A custom, patient-specific unicompartmental knee replacement was developed using
      a unsupervised neural network trained on a database of healthy knee geometries.
      This custom implant was then compared to a conventional implant in terms of
      contact stress in a Finite Element Model. The custom implant experienced lower
      contact stresses at the tibiofemoral joint compared to the conventional implant.
      The custom implant stresses were further reduced with the use of a customized
      mobile bearing. The custom implant also displayed more uniform stress
      distribution at the bone-implant interface.

PMID- 21095806
TI  - The sacroiliac spine - computer simulation of motion and modeling of the
      ligaments.
AB  - Using an interactive, 3D, kinematic simulation of the human skeleton, the motion
      of the sacro-iliac (SI) joint is modeled based upon descriptions available in the
      literature. The major ligaments are added to the simulation data structure using
      deformable cubic B-spline curve paths. Ligament strains were generated and
      studied in response to the motion simulations. Results improve our understanding
      of sacro-iliac kinematics and highlight the importance of further studies to
      elucidate pathological as well as normal SI joint and ligament function.

PMID- 21095807
TI  - Self-powered instrumented knee implant for early detection of postoperative
      complications.
AB  - In-vivo measurement of tibiofemoral forces transmitted through Total Knee
      Replacement (TKR) during normal walking allows the early detection of
      postoperative complications such as the tibiofemoral misalignment and soft-tissue
      imbalance. In addition, the in-vivo data can help to improve the design of TKR in
      order to reduce polyethylene wear and consequently to increase the lifespan of
      knee implant. A self-powered custom-designed tibial implant instrumented with
      four piezoceramics has been developed in order to detect the aforementioned
      complications by measuring the relative change in pressure center (COP) position
      for different levels of eccentric compressive loading. Moreover, the energy
      harvested by the piezoceramics can be used to power a transmission system located
      at the stem of knee implant to wirelessly transmit the in-vivo data outside the
      implant for further processing and display.

PMID- 21095808
TI  - Repeatability of an off-the-shelf, full body inertial motion capture system
      during clinical gait analysis.
AB  - BACKGROUND AND AIMS: To establish gait analysis as part of routine clinical
      diagnoses, physicians demand accurate and flexible motion capture (Mocap).
      Currently, popular optical, mechanical and acoustic Mocap systems offer
      acceptable repeatability, but fall short of the spatial and economic benefits
      accompanying inertial motion capture (IMC). However, IMC is considered adolescent
      due to limited testing in gait analysis. This paper aims to address this
      hindrance through within-day and between test day repeatability studies. METHODS:
      To determine the repeatability of IMC, routine gait studies were done on 30 able
      bodied males. Repeatability was quantified using the coefficient of multiple
      determination (CMD) and the coefficient of multiple correlation (CMC). RESULTS:
      IMC-recorded kinematics were highly repeatable for within-day (CMD: 0.786-0.984
      or CMC: 0.881-0.992) and between-day trials (CMD: 0.771-0.991 or CMC: 0.872
      0.995). The results compare well to those from similar repeatability studies in
      the literature based on optical Mocap systems.

PMID- 21095809
TI  - Sources of non-physiologic noise in simultaneous EEG-fMRI data: a phantom study.
AB  - Simultaneous EEG-fMRI studies require an understanding of the noise
      characteristics of the acquisition environment so that appropriate pre-processing
      steps may be taken to remove known artifacts from the data stream. Using a
      phantom approach, we have developed a general methodology for characterizing non
      physiologic noise in EEG signal and demonstrate the use of this methodology for a
      specific MR scanner and EEG data acquisition system configuration. Our results
      show the delta frequency band is significantly impacted by baseline drift or
      baseline correction algorithms while the beta and gamma bands are impacted by
      residual gradient artifact and gradient corrections.

PMID- 21095810
TI  - Detection of EEG electrodes in brain volumes.
AB  - This paper presents a method to detect 128 EEG electrodes in image study and to
      merge with the Nuclear Magnetic Resonance volume for better diagnosis. First we
      propose three hypotheses to define a specific acquisition protocol in order to
      recognize the electrodes and to avoid distortions in the image. In the second
      instance we describe a method for segmenting the electrodes. Finally,
      registration is performed between volume of the electrodes and NMR.

PMID- 21095811
TI  - Localization of class-related mu-rhythm desynchronization in motor imagery based
      brain-computer interface sessions.
AB  - We localize the sources of class-dependent event-related desynchronisation (ERD)
      of the mu-rhythm related to different types of motor imagery in Brain-Computer
      Interfacing (BCI) sessions. Our approach is based on localization of single-trial
      Fourier coefficients using sparse basis field expansions (S-FLEX). The analysis
      reveals focal sources in the sensorimotor cortices, a finding which can be
      regarded as a proof for the expected neurophysiological origin of the BCI control
      signal. As a technical contribution, we extend S-FLEX to the multiple measurement
      case in a way that the activity of different frequency bins within the mu-band is
      coherently localized.

PMID- 21095812
TI  - DYNAMO: dynamic multi-model source localization method for EEG and/or MEG.
AB  - This paper proposes a multiple model method that addresses the estimation of the
      EEG/MEG neural sources as a multihypothesis, multidimensional and dynamic
      estimation problem. The key aspect is the probabilistic integration of several
      neural models to simultaneously estimate and integrate the brain activity of
      different dynamic neural processes that are characterized by the number of
      sources, the dynamic of those sources and the initial conditions. The method was
      validated with EEG data gathered in a protocol to elicit error-related
      potentials, since there is evidence of the brain region that generate those
      signals. The results reveal that the proposed multiple model method is able to
      identify the brain structure associated with error processing, which is a
      preliminary indicator of the validity of the proposed method.

PMID- 21095813
TI  - Variation-based sparse cortical current density imaging in estimating cortical
      sources with MEG data.
AB  - We investigated the performance of a new sparse neuroimaging method, i.e.,
      Variation-Based Sparse Cortical Current Density (VB-SCCD) using
      magnetoencephalography (MEG) data to reconstruct extended cortical sources and
      their spatial distributions on the cortical surface. We conducted Monte Carlo
      simulation studies to compare the performance of the VB-SCCD method with
      different number of cortical sources and different number of MEG sensors. Our
      simulation data suggests that the VB-SCCD method is able to reconstruct extended
      cortical sources with the overall accuracy, while it has significantly reduced
      performance when cortical sources are radially oriented to MEG sensors. It has
      higher accuracy when the number of sensors is large and the source configuration
      is simple. We further assess the performance of VB-SCCD in real MEG data from an
      epilepsy patient and reconstructed cortical sources behind interictal spikes from
      the patient which are consistent with the clinical evaluation outcomes. This data
      indicate its promising applications in clinical problems related to neurological
      disorders.

PMID- 21095814
TI  - 3D reconstruction of wireless capsule endoscopy images.
AB  - Wireless capsule endoscopy (WCE) has been gradually applied for inspecting the
      gastrointestinal (GI) tract. However, WCE can only provide monocular view.
      Moreover, only a small part of GI wall is visible frame by frame due to the
      limited illumination and irregular motion of the capsule endoscope. The
      perception of entire GI structure could be hard even for the experienced
      endoscopists. A realistic friendly three dimension view is needed to help the
      physicians to get a better perception of the GI tract. In this paper, we present
      a method to reconstruct the three dimension surface of the intestinal wall by
      applying the SIFT feature detector and descriptor to a sequence of WCE images.
      Epipolar geometry is employed to further constrain the matching feature points in
      order to obtain a more accurate 3D view. The experiments on real data are
      presented to show the performance of our proposed method.

PMID- 21095815
TI  - Using magnetic resonance imaging measurements for the determination of local wave
      speed and arrival time of reflected waves in human ascending aorta.
AB  - Wave speed is one of the key factors describing wave propagation in arteries [1].
      Local wave speed is directly related to the arterial wall properties [2]. With
      aging, arterial wave speed increases due to the stiffening of arterial wall, and
      also related to arterial disease.

PMID- 21095816
TI  - Structured light imaging of epicardial mechanics.
AB  - There is a need for accurate measurements of mechanical strain and motion of the
      heart both in vitro and in vivo. We have developed a new structured-light imaging
      system capable of epicardial shape measurement at 333 fps at a resolution of 768
      * 768 pixels. Here we present proof-of-concept data from our system applied to a
      beating rabbit heart in vitro to measure epicardial mechanics. This method will
      allow high resolution mapping of epicardial strain and virtual immobilization of
      the heart for removal of motion artifacts from epicardial recordings with
      fluorescence dyes. This will allow mapping of transmembrane potential and calcium
      transients in a beating heart, including in vivo.

PMID- 21095817
TI  - Observation of capillary flow in human skin during tissue compression using CCD
      video-microscopy.
AB  - Recent technological advances of the CCD video-camera have made microscopes more
      compact and greatly improved their sensitivity. We newly designed a compact
      capillaroscopy which was composed with a CCD video-probe equipped a contact-type
      objective lens and illuminator. In the present study, we evaluated usefulness of
      the instrument for a bed-side human capillaroscopy to observe the capillary flow
      in various dermal regions. The influences of tissue compression on the dermal
      capillary blood flow were also investigated to confirm the utility for clinical
      applications. Our capillaroscopy visualized the nutritional capillary blood flow
      in almost all parts of skin surface. Our observations showed that a level of
      vertical stress similar to arterial pressure was required to stop the capillary
      flow. From these demonstrations the present CCD video-probe based capillaroscopy
      would be useful for clinical applications as a bed-side human capillaroscopy.

PMID- 21095818
TI  - A new gradient-based algorithm for edge detection in ultrasonic carotid artery
      images.
AB  - In human clinical studies, digital B-Mode ultrasound images of carotid and
      femoral artery walls are used to measure Intima-Media Thickness (IMT). IMT
      represents the arterial intima-media complex and is a validated surrogate
      parameter for atherosclerosis and cardiovascular disease risk. Conventionally,
      IMT is obtained by tracing the ultrasound interfaces of the arterial far walls
      manually. The manual tracing, however, may be replaced by an automated approach
      in order to decrease image analysis variability and improve consistency and
      efficiency of the imaging laboratory. In this paper, we present and test a novel
      automated edge detection method which employs a multi-step gradient based
      algorithm. The new method principally uses intensity, intensity gradient, and
      interface continuity of pixels to determine the ultrasound interfaces. In our
      investigations, we used the far wall of the common carotid artery to test the
      proposed algorithm. As our results show, the novel algorithm greatly eliminates
      subjectivity associated with conventional manual tracing and semi-automated
      gradient methods that employ seed point selection. The new method can therefore
      have a great potential in atherosclerosis studies and clinical trials.

PMID- 21095819
TI  - Silicone rubber trileaflet valve assessment using cardiovascular magnetic
      resonance imaging.
AB  - Hydrodynamic valve performance is usually evaluated by effective orifice area
      (EOA), geometric orifice area (GOA) and transvalvular pressure gradients (PG).
      Magnetic resonance imaging (MRI) is a very efficient tool for assessing these
      parameters. In this study, we evaluated a silicone rubber trileaflet valve using
      MRI. EOA, GOA and PG were evaluated under steady (12 l/min - 20 l/min) and
      pulsatile (5 l/min) flow conditions using continuity equation, planimetry and
      simplified Bernoulli's equation respectively; the contraction coefficient (Cc)
      and Reynolds number (Re) were also evaluated as hydrodynamic parameters. The
      highest EOAs were 0.75 cm(2) for steady flow conditions and 0.98 cm(2) for
      pulsatile flow. For pulsatile flow conditions greater GOA by planimetry was 1.43
      cm(2). For both flow conditions the highest PGs were > 40 mmHg. Cc was on range
      from 0.8 to 0.86 under steady flow conditions and 0.68 for pulsatile flow at peak
      sytole. The Re was much greater than 2200 for all flow conditions. This study
      allowed the non invasive evaluation of a silicone rubber trileaflet valve under
      steady and pulsatile conditions with MRI in order to understand valve opening.

PMID- 21095820
TI  - Patient based abdominal aortic aneurysm rupture risk prediction combining
      clinical visualizing modalities with fluid structure interaction numerical
      simulations.
AB  - Fluid structure interaction (FSI) simulations of patient-specific fusiform non
      ruptured and contained ruptured Abdominal Aortic Aneurysm (AAA) geometries were
      conducted. The goals were: (1) to test the ability of our FSI methodology to
      predict the location of rupture, by correlating the high wall stress regions with
      the rupture location, (2) estimate the state of the pathological condition by
      calculating the ruptured potential index (RPI) of the AAA and (3) predict the
      disease progression by comparing healthy and pathological aortas.

PMID- 21095821
TI  - Multiscale imaging of the human heart: Building the foundation for human systems
      physiology and translational medicine.
AB  - The development of human cardiovascular systems physiology is inhibited by the
      lack of multiscale functional physiological data, which represents human heart
      physiology at the molecular, cellular, tissue, organ, and system levels. We have
      developed an experimental approach to study explanted human hearts in vitro at
      multiple physiological scales with a wide array of imaging modalities. This
      approach has already yielded data indicating significant differences between
      animal models of diseases and actual human heart disease. Our data provides a
      quantitative foundation for multiscale physiological models of the cardiovascular
      system and will allow improvement in translation of medical technology and
      pharmacology from animal models to therapy.

PMID- 21095822
TI  - E-Textile platforms for rehabilitation.
AB  - This paper focus on SFIT platforms for rehabilitations and FES therapy. Two
      systems will be described, one developed to support patients during motor
      therapy, when they are still hospitalized, and after discharge, at home; the
      other is a sleeve integrating multi-electrodes patches, designed to allow FES
      therapy and EMG acquisition for patients affected by tremor. These examples prove
      that it is possible to combine fabric electrodes and biomechanical textile
      sensors to conceive systems where gesture recognition function can be combined
      with EMG detection and FES capability. These platforms can be easily used at home
      for daily therapy, as well as for telemedicine services.

PMID- 21095823
TI  - Behavioral pattern detection from Personalized Ambient Monitoring.
AB  - Bipolar disorder (BD) is a serious psychiatric condition that affects a large
      number of people. Many people with BD self-monitor their condition in order to
      try and keep the disturbances from affective episodes to a minimum. The
      Personalized Ambient Monitoring (PAM) project has developed a system that
      performs behavioral monitoring in an unobtrusive manner and can detect changes in
      a person's behavior. The system uses a variety of discreet sensors to gather data
      on the parson's behavior and this data is processed to extract behavioral
      patterns and detect changes in those patterns. In this paper we present one
      method of data processing that takes 24hr long data-streams from the sensors, pre
      processes them and uses the Continuous Profile Model to align and extract the
      underlying patterns from the data-streams. We present some preliminary results
      from a technical trial.

PMID- 21095824
TI  - A system for monitoring cardiac vibration, respiration, and body movement in bed
      using an infrared.
AB  - We have developed a non-invasive system for monitoring cardiac vibrations,
      respiration and body movement of in-bed hospitalized patients and elderly people
      who need constant care. These physiological parameters are recorded by an
      infrared emitting diode and a photo transistor, which are attached between spring
      coils in bed mattress. The infrared emitting diode diffuses infrared light into
      the mattress. The diffusion of this energy is changed by mattress shape
      variations and spring coil vibrations, which modulate the intensity of the
      received infrared signal. The intensity is also modulated by physiological
      parameters such as heart pulse, respiration and body movement. The physiological
      parameters are detected from the received infrared intensity signal by low, high
      and band pass filters.

PMID- 21095825
TI  - Predicting severity of Parkinson's disease from speech.
AB  - Parkinson's disease is known to cause mild to profound communication impairments
      depending on the stage of progression of the disease. There is a growing interest
      in home-based assessment tools for measuring severity of Parkinson's disease and
      speech is an appealing source of evidence. This paper reports tasks to elicit a
      versatile sample of voice production, algorithms to extract useful information
      from speech and models to predict the severity of the disease. Apart from
      standard features from time domain (e.g., energy, speaking rate), spectral domain
      (e.g., pitch, spectral entropy) and cepstral domain (e.g, mel-frequency warped
      cepstral coefficients), we also estimate harmonic-to-noise ratio, shimmer and
      jitter using our recently developed algorithms. In a preliminary study, we
      evaluate the proposed paradigm on data collected through 2 clinics from 82
      subjects in 116 assessment sessions. Our results show that the information
      extracted from speech, elicited through 3 tasks, can predict the severity of the
      disease to within a mean absolute error of 5.7 with respect to the clinical
      assessment using the Unified Parkinson's Disease Rating Scale; the range of
      target motor sub-scale is 0 to 108. Our analysis shows that elicitation of speech
      through less constrained task provides useful information not captured in widely
      employed phonation task. While still preliminary, our results demonstrate that
      the proposed computational approach has promising real-world applications such as
      in home-based assessment or in telemonitoring of Parkinson's disease.

PMID- 21095827
TI  - Measurement of the complex permittivity of microbubbles using a cavity
      perturbation technique for contrast enhanced ultra-wideband breast cancer
      detection.
AB  - Measurements of the complex permittivity of various concentrations of
      microbubbles in ethylene glycol liquid phantom have been carried out. A cavity
      perturbation technique using custom rectangular waveguide cavities, which are
      sensitive to small changes in the permittivity of the perturber, has been
      employed. Three different frequencies within the ultra-wideband (UWB) frequency
      spectrum have been used for the experiments. The results show that the
      concentration of the air filled microbubbles required to achieve a dielectric
      contrast as little as 2% exceeds the recommended dosage used in clinical
      ultrasound applications, by more than two orders of magnitude.

PMID- 21095826
TI  - Model-based data integration in clinical environments.
AB  - As a result of improved hospital information-technology infrastructure and
      declining costs of storage media, vast amounts of physiological waveform and
      trend data can now be continuously collected and archived from bedside monitors
      in operating rooms, intensive care units, or even regular hospital rooms. The
      real-time or off-line processing of such volumes of high-resolution data, in
      attempts to turn raw data into clinically actionable information, poses
      significant challenges. However, it also presents researchers - and eventually
      clinicians - with unprecedented opportunities to move beyond the traditional
      individual-channel analysis of waveform data, and towards an integrative patient
      monitoring framework, with likely improvements in patient care and safety. We
      outline some of the challenges and opportunities, and propose strategies for
      model-based integration of physiological data to improve patient monitoring.

PMID- 21095828
TI  - Fractal analysis of contours of breast masses in mammograms via the power spectra
      of their signatures.
AB  - Contours of benign breast masses and malignant tumors in mammograms differ
      substantially in their shape and complexity; the former are usually round and
      smooth, whereas the latter are typically spiculated and irregular. We demonstrate
      the usefulness of fractal analysis via a frequency domain approach applied to one
      dimensional signatures of the two-dimensional contours of breast masses. The 1/f
      model was applied to power spectra of signatures to estimate the fractal
      dimension. Tests with a dataset of 111 contours, including those of 65 benign
      masses and 46 malignant tumors, indicated a high classification performance of
      0.89 in terms of the area under the receiver operating characteristic curve.

PMID- 21095829
TI  - Automated video-based measurement of eye closure for detecting behavioral
      microsleep.
AB  - A device capable of continuously monitoring an individual's levels of alertness
      in real-time is highly desirable for preventing drowsiness and microsleep related
      accidents. This paper presents a development of non-intrusive and light
      insensitive video-based system that uses computer-vision methods to measure
      facial metric for identifying visible facial signs of drowsiness and behavioral
      microsleep. The developed system uses a remotely placed camera with a near
      infrared illumination to acquire the video. The computer-vision methods are then
      applied to sequentially localize face, eyes, and eyelids positions to measure
      ratio of eye closure. The system was evaluated in frontal images of nine subjects
      with varying facial structures and exhibiting several ratio of eye closure and
      eye gaze under fully dark and ambient lighting conditions. The preliminary
      results showed promising results with sufficient accuracy to distinguish between
      fully closed, half closed, and fully open eyes.

PMID- 21095830
TI  - Detection of exudates in retinal images using a pure splitting technique.
AB  - Diabetic retinopathy is a major cause of blindness. Earliest signs of diabetic
      retinopathy are damage to blood vessels in the eye and then the formation of
      lesions in the retina. This paper presents an automated method for the detection
      of bright lesions (exudates) in retinal images. In this work, an adaptive
      thresholding based on a novel algorithm for pure splitting of the image is
      proposed. A coarse segmentation based on the calculation of a local variation for
      all image pixels is used to outline the boundaries of all candidates which have
      clear borders. A morphological operation is used to refine the adaptive
      thresholding results based on the coarse segmentation results. Using a clinician
      reference standard (ground truth), images with exudates were detected with 91.2%
      sensitivity, 99.3% specificity, and 99.5% accuracy. Due to its results the
      proposed method can achieve superior performance compared to existing techniques
      and is robust to image quality variability.

PMID- 21095831
TI  - Automated classification of renal cell carcinoma subtypes using bag-of-features.
AB  - Color variation in medical images degrades the classification performance of
      computer aided diagnosis systems. Traditionally, color segmentation algorithms
      mitigate this variability and improve performance. However, consistent and robust
      segmentation remains an open research problem. In this study, we avoid the
      tenuous phase of color segmentation by adapting a bag-of-features approach using
      scale invariant features for classification of renal cell carcinoma subtypes.
      Previous work shows that features from each subtype match those from expertly
      chosen template images. In this paper, we show that the performance of this match
      based methodology greatly depends on the quality of the template images. To avoid
      this uncertainty, we propose a bag-of-features approach that does not require
      expert knowledge and instead learns a "vocabulary" of morphological
      characteristics from training data. We build a support vector machine using
      feature histograms and evaluate this method using 40 iterations of 3-fold cross
      validation. We achieve classification accuracy above 90% for a heterogeneous
      dataset labeled by an expert pathologist, showing its potential for future
      clinical applications.

PMID- 21095832
TI  - Activation of ganglion cell axons following epiretinal electrical stimulation
      with hexagonal electrodes.
AB  - A hexagonal electrode configuration has been proposed as an advantageous
      alternative to conventional electrode arrangements used in retinal prosthesis
      design. In the present study, the aim was to characterize retinal ganglion cell
      axonal responses to epiretinal electrical stimulation. 50 and 125 microm disk
      electrodes, arranged in a hexagonal configuration, were tested using in vitro
      rabbit retinal preparations. 100 micros/phase anodic-first biphasic current
      pulses were applied to the inner retinal surface, and ganglion cell responses
      were recorded differentially with extracellular microelectrodes. Axonal
      activation thresholds were 4.7 +/- 2.5 microA for 50 microm, and 9.3 +/- 4.0
      microA for 125 microm electrodes. With anodic monophasic pulses there was a 3.3
      +/- 0.8 times increase in threshold, compared to anodic-first biphasic
      stimulation. Thresholds increased up to 20 times when stimulating electrodes were
      lifted 100 microm above the retinal surface. Overall, axonal activation
      thresholds were within the safe charge injection limits for platinum electrodes,
      given that these electrodes were positioned in close proximity to the retinal
      surface.

PMID- 21095833
TI  - Diamond penetrating electrode array for epi-retinal prosthesis.
AB  - This paper presents progress in the characterization and application of diamond
      penetrating electrode arrays for Epi-Retinal Prostheses. Electrical stimulation
      of degenerate retina has already been shown to restore partial vision for some
      blind patients, albeit at low spatial resolution. Higher resolution may be
      achievable by building arrays with electrodes that have greater areal density and
      closer proximity to target neurons. However, high standards of biocompatibility
      and hermeticity must be maintained, limiting the range of available materials of
      manufacture. Here, the design and histology of high density electrode arrays
      (approximately 100 electrodes/mm(2)) made from polycrystalline diamond and
      implanted into rat retinae are discussed. Results from initial steps in this
      process are reported.

PMID- 21095835
TI  - Focal activation of primary visual cortex following supra-choroidal electrical
      stimulation of the retina: Intrinsic signal imaging and linear model analysis.
AB  - We performed optical intrinsic signal imaging of cat primary visual cortex (Area
      17 and 18) while delivering bipolar electrical stimulation to the retina by way
      of a supra-choroidal electrode array. Using a general linear model (GLM) analysis
      we identified statistically significant (p < 0.01) activation in a localized
      region of cortex following supra-threshold electrical stimulation at a single
      retinal locus. OUR RESULTS: (1) demonstrate that intrinsic signal imaging
      combined with linear model analysis provides a powerful tool for assessing
      cortical responses to prosthetic stimulation, and (2) confirm that supra
      choroidal electrical stimulation can achieve localized activation of the cortex
      consistent with focal activation of the retina.

PMID- 21095834
TI  - Retinal ganglion cell (RGC) responses to different voltage stimulation parameters
      in rd1 mouse retina.
AB  - Retinal prostheses are being developed to restore vision for the blind with
      retinal diseases such as retinitis pigmentosa (RP) or age-related macular
      degeneration (AMD). Since neural prostheses depend upon electrical stimulation to
      control neural activity, optimal stimulation parameters for successful encoding
      of visual information are one of the most important requirements to enable visual
      perception. Therefore, in this paper, we focused on RGC responses to different
      stimulation parameters in degenerated retina. For this purpose, we used in vitro
      preparation of rd1 mice retina on microelectrode arrays. When the neural network
      of rd1 mice retinas is stimulated with voltage-controlled pulses, RGCs in
      degenerated retina also respond to voltage amplitude or voltage duration
      modulation as well in wild-type RGCs. But the temporal pattern of RGCs response
      is very different; in wild-type RGCs, single peak within 100 ms appears while in
      RGCs in degenerated retina multiple peaks (approximately 4 peaks) with
      approximately 10 Hz rhythm within 400 ms appear. The threshold charge densities
      for activation of RGCs in rd1 mouse retinas were on average 70.50 approximately
      99.87 microC/cm(2) in the experiment of voltage amplitude modulation and 120.5
      approxiamtely 170.6 microC/cm(2) in the experiment of voltage duration
      modulation.

PMID- 21095836
TI  - Conducting polymer electrodes for visual prostheses.
AB  - Conducting polymers (CPs) have the potential to provide superior neural
      interfaces to conventional metal electrodes by introducing more efficient charge
      transfer across the same geometric area. In this study the conducting polymer
      poly(ethylene dioxythiophene) (PEDOT) was coated on platinum (Pt) microelectrode
      arrays. The in vitro electrical characteristics were assessed during biphasic
      stimulation regimes applied between electrode pairs. It was demonstrated that
      PEDOT could reduce the potential excursion at a Pt electrode interface by an
      order of magnitude. The charge injection limit of PEDOT was found to be 15 x
      larger than Pt. Additionally, PEDOT coated electrodes were acutely implanted in
      the suprachoroidal space of a cat retina. It was demonstrated that PEDOT coated
      electrodes also had lower potential excursions in vivo and electrically evoked
      potentials (EEPs) could be detected within the vision cortex.

PMID- 21095837
TI  - Uncertainty and complexity in personal health records.
AB  - New technologies in medicine have led to an explosion in the number of parameters
      that must be considered when diagnosing and treating a patient. Because of this
      high volume of data it is not possible for the human decision maker to take all
      information into account in arriving at a decision. Automated methods are needed
      to effectively evaluate electronic information in many formats and provide
      summaries to the medical professional. The task is complicated by the complexity
      of the data and the potential uncertainty of some of the results. In this article
      complexity and uncertainty in medical data are discussed in terms of both
      representation and types of analysis. Methods that can address multiple complex
      data types are illustrated and examples are provided for specific medical
      problems. These methods are particularly important for automated trend analysis
      in the personal health record as small errors can be propagated through the
      complex system resulting in incorrect diagnosis and treatment.

PMID- 21095838
TI  - Anaesthesia synchronization software: target controlled infusion system
      evaluation.
AB  - Target Controlled Infusion (TCI) systems are based in drug Pharmacokinetic (Pk)
      and Pharmacodynamic (Pd) models implemented in an algorithm to drive an infusion
      device. Several studies had compare manual titration of anesthesia and TCI system
      use; some studies evaluate the performance of the control algorithms for TCI
      systems, and a considerable number of studies assess the performance of Pk/Pd
      models implemented into TCI systems. This study presents a set of tests to
      validate the performance of a TCI system as a computer-aided. The goal of the
      current study was to assess the performance of the TCI system, Anaesthesia
      Synchronization Software (ASYS), on clinical set up to evaluate communication
      consistence (computer - infusion device) and controller performance in real time.
      These measures provided quantitative and qualitative evidences of software
      robustness and accuracy to be used at clinical environment.

PMID- 21095839
TI  - Intelligent clinical decision support systems based on SNOMED CT.
AB  - The decision support systems that have been developed to assist physicians in the
      diagnostic process often are based on static data which may be out of date. We
      present a comprehensive analysis of artificial intelligent methods which could be
      applied to documents encoded by SNOMED CT. By mining information directly from
      SNOMED CT encoded documents, a decision support system could contain timely
      updated diagnostic information, which is of significant value in fast changing
      situations such as minimally understood emerging diseases and epidemics. Through
      a high level comparison of many AI methods it is found that a TAN-Bayesian method
      could be the most suitable to apply to SNOMED CT data.

PMID- 21095840
TI  - Real-time prognosis of ICU physiological data streams.
AB  - This paper presents a system capable of predicting in real-time the evolution of
      Intensive Care Unit (ICU) physiological patient data streams. It leverages a
      state of the art stream computing platform to host analytics capable of making
      such prognosis in real time. The focus is on online algorithms that do not
      require a training phase. We use Fading-Memory Polynomial filters [8] on the
      frequency domain to predict windows of ICU data streams. We report on both the
      system and the performance of this approach when applied to traces of more than
      1500 ICU patients obtained from the MIMIC-II database [1].

PMID- 21095841
TI  - Using tele-medical electrocardiography monitoring and analysis for a more
      immediate prognosis to patients of suspect Long QT Syndrome.
AB  - Currently Long QT Syndrome (LQTS) is diagnosed by using the Long QT Syndrome
      "diagnostic score". Calculation of the score is done by assigning different
      points to various criteria. The answers to the criteria are often hard to obtain
      as they require lengthy periods of cardiac observations. And even after the
      scores are obtain, only a percentage of certainty is obtained. Diagnosis of LQTS
      is often hard as 2.5% of the healthy population has prolonged QT interval.
      Conversely, 10-15% of LQTS patients have normal QT intervals. In this paper an
      approach to prognose a patient suspect of LQTS is proposed. It involves
      monitoring the QTc interval trend lines of the suspected patient. Through trend
      analysis, it seeks to discern the patients with LQTS from the healthy patients.

PMID- 21095842
TI  - Integrated approach for the study of anatomical variability in the cardiac
      Purkinje system: from high resolution MRI to electrophysiology simulation.
AB  - The ordered electrical stimulation of the ventricles is achieved by a specialized
      network of fibres known as the Purkinje system. The gross anatomy and basic
      functional role of the Purkinje system is well understood. However, very little
      is known about the detailed anatomy of the Purkinje system, its inter-individual
      variability and the implications of the variability in ventricular function, in
      part due to limitations in experimental techniques. In this study, we aim to
      provide new insight into the inter-individual variability of the free running
      Purkinje system anatomy and its impact on ventricular electrophysiological
      function. As a first step towards achieving this aim, high resolution magnetic
      resonance imaging (MRI) datasets of rat and the rabbit ventricles are obtained
      and analysed using a novel semi-automatic image processing algorithm for
      segmentation of the free-running Purkinje system. Segmented geometry from the MRI
      datasets is used to construct a computational model of the Purkinje system, which
      is incorporated in to an anatomically-based ventricular geometry to simulate
      ventricular electrophysiological activity.

PMID- 21095843
TI  - Comparing finite elements and finite differences for developing diffusive models
      of glioma growth.
AB  - Glioma is the most aggressive type of brain tumor. Several mathematical models
      have been developed during the last two decades, towards simulating the
      mechanisms that govern the development of glioma. The most common models use the
      diffusion-reaction equation (DRE) for simulating the spatiotemporal variation of
      tumor cell concentration. The proposed diffusive models have mainly used finite
      differences (FDs) or finite elements (FEs) for the approximation of the solution
      of the partial differential DRE. This paper presents experimental results on the
      comparison of the FEs and FDs, especially focused on the glioma model case. It is
      studied how the different meshes of brain can affect computational consistency,
      simulation time and efficiency of the model. The experiments have been studied on
      a test case, for which there is a known algebraic expression of the solution.
      Thus, it is possible to calculate the error that the different models yield.

PMID- 21095844
TI  - AngioLab: integrated technology for patient-specific management of intracranial
      aneurysms.
AB  - AngioLab is a software tool developed within the GIMIAS framework and is part of
      a more ambitious pipeline for the integrated management of cerebral aneurysms.
      AngioLab currently includes three plug-ins: angio segmentation, angio morphology
      and stenting, as well as supports advanced rendering techniques for the
      visualization of virtual angiographies. In December 2009, 23 clinicians completed
      an evaluation questionnaire about AngioLab. This activity was part of a teaching
      course held during the 2(nd) European Society for Minimally Invasive
      Neurovascular Treatment (ESMINT) Teaching Course held at the Universitat Pompeu
      Fabra, Barcelona, Spain. The Automated Morphological Analysis (angio morphology
      plug-in) and the Endovascular Treatment Planning (stenting plug-in) were
      evaluated. In general, the results provided by these tools were considered as
      relevant and as an emerging need in their clinical field.

PMID- 21095845
TI  - Effects of time varying currents and magnetic fields in the frequency range of 1
      kHz to 1 MHz to the human body - a simulation study.
AB  - Exposure to time-varying magnetic fields evokes two effects in biological tissue:
      Firstly, an electric field is induced that generates eddy currents in conductive
      tissues, and, secondly, power deposit might increase local temperatures. Field
      effects of frequencies up to 1 kHz and above 1 MHz are well known. The
      intermediate frequency range lacks intensive research. Only little attention has
      been paid so far. Yet due to recent innovations in medical diagnostics and
      therapies like Magnetic Particle Imaging or RF-Hyperthermia, the need arises to
      investigate the frequency range from 1kHz to 1 MHz. This work presents results of
      numerical field calculations of a human body model placed within simple coil
      configurations. Induced current densities, generated by alternating coil
      currents, are simulated. The effect of current densities are demonstrated and
      evaluated on schematic cell models of excitable tissue. In order to generate an
      action potential at the cell membrane, a difference in electric potential from
      intra- to extracellular space must be present. It can be shown that in case of
      sufficient field strength, stimulation of nerves and muscles is possible up to a
      frequency of 100 kHz. The aim of this paper is to transfer simulation results
      from the macroscopic model to the microscopic model in order to estimate field
      effects of big field generating coils.

PMID- 21095846
TI  - Evaluation framework for the multilevel macroscopic models of solid tumor growth
      in the glioma case.
AB  - This paper investigates the applicability of multilevel macroscopic models for
      simulating solid tumor growth in the invasive glioblastoma multiforme (GBM) case.
      The continuum case approach tumor model based on the diffusion reaction equation
      is evaluated on a pre-segmented tomographic atlas where all tissue properties are
      known a priori. The atlas is further registered on a real clinical case where the
      tumor invasion status is gauged in two successive points in time. Based on the
      latter, the model attempts to fully replicate tumor growth taking into account
      tissue based properties as identified from the atlas template. The whole process
      is performed on a clinical platform specially designed to facilitate precise
      identification and delineation of tumors of large number of 3D tomographic
      datasets by an expert clinician. The promising results presented encourage the
      potential clinical applicability of the proposed model in the glioma case and
      identify crucial points and direction of further model refinement and research.

PMID- 21095847
TI  - Towards a realistic dielectric tissue model: a multiscale approach.
AB  - In the past, mainly analytical mixing formulas were used for modeling of
      dielectric properties of biological cells. General drawbacks of such formulas are
      the restriction to simple shapes and small cellular volume fractions. Assuming
      cell suspensions or tissues being quasi-periodic the problem size can be reduced
      to a cubic unit cell containing a single biological cell. Under this assumption
      numerical, e.g. Finite- Element models of such unit cells provide effective
      dielectric parameters for the entire tissue or cell suspension. In this work a
      flexible shape parametrization method allowing for a realistic representation of
      biological cells is applied to eight different cell types. A non-axisymmetric
      columnar epithelium cell occurring e.g. in the epidermis is chosen as an example.
      Numerical simulations of the columnar cell exposed to a time-harmonic electric
      field are performed for two different, high volume fractions, followed by the
      extraction of effective dielectric parameters of the bulk material. The
      simulation results are compared to two analytical approximations for ellipsoidal
      particles. The results suggest, that the calculation of effective dielectric
      properties of arbitrarily shaped cells in the frequency range between 100kHz and
      1GHz requires at least a numerical cell model.

PMID- 21095848
TI  - Auditory streaming and listening effort: an event related potential study.
AB  - Until now, an objective method to estimate listening effort with a minimum level
      of cooperation of the patient in order to fit hearing aids is not existent. The
      benefit of such a method would be to reduce the listening effort in hearing
      impaired persons by an adequate adaption of the hearing aids. Recently, we have
      shown that the wavelet phase synchronization stability (WPSS) of auditory late
      responses could serve as a measure to estimate listening effort. In this paper,
      we extend our previous studies by using for the first time syllable stimulation
      paradigms with two levels of difficulty due to the combination of the syllables.
      Furthermore, by taking the model of auditory stream selection into account, the
      complexity of the paradigms was enhanced by the generation of a second competing
      auditory stream beside the syllable stream. This stream consisted of multitalker
      babble noise at two different signal to noise ratios in order to mimic noisy
      environments. The data was collected from a total of 21 normal hearing subjects,
      who had always to detect a target syllable. It is concluded, that the WPSS is a
      robust measure to perceive differences between the effort needed to solve a task
      in an easy and a difficult listening condition. However, a further research will
      be to test hearing impaired persons to prove, if this electrophysiological method
      could be applied to improve the hearing aid fitting procedures in clinical
      settings.

PMID- 21095849
TI  - Transcranial magnetic stimulation in the presence of deep brain stimulation
      implants: Induced electrode currents.
AB  - The safety of transcranial magnetic stimulation (TMS) in patients with an
      implanted deep brain stimulation (DBS) systems has not been thoroughly
      investigated. One potential safety hazard is the induction of significant
      voltages in the subcutaneous leads in the scalp that could result in unintended
      electrical currents in the DBS electrode contacts. We measured ex-vivo the TMS
      induced voltages and currents in DBS electrodes with the implantable pulse
      generator (IPG) set in various modes of operation. We show that voltages as high
      as 100 V resulting in currents as high as 83 mA can be induced in the DBS leads
      by a TMS pulse in all IPG modes. These currents are an order of magnitude higher
      than the normal DBS pulses, and could result in tissue damage. When the IPG is
      turned off, electrode currents flow only if the TMS-induced voltage exceeds 5 V.

PMID- 21095850
TI  - Habituation analysis of chirp vs. tone evoked auditory late responses.
AB  - We have recently shown that tone evoked auditory late responses are able to proof
      that habituation is occurring [1], [2]. The sweep to sweep analysis using time
      scale coherence method from [1] is used. Where clear results using tone evoked
      ALRs were obtained. Now it is of interest how does the results behave using chirp
      evoked ALRs compared to tone evoked ALRs so that basilar membrane dispersion is
      compensated. We presented three different tone bursts and three different band
      limited chirps to 10 subjects using two different loudness levels which the
      subjects determined themselves before as medium and uncomfortably loud. The 3
      chirps are band limited within 3 different ranges, the chirp with the lowest
      center frequency has the smallest range (according to octave-band). Chirps and
      tone bursts are using the same center frequencies.

PMID- 21095851
TI  - Feasibility and performance evaluation of generating and recording visual evoked
      potentials using ambulatory Bluetooth based system.
AB  - Report contains the design overview and key performance measurements
      demonstrating the feasibility of generating and recording ambulatory visual
      stimulus evoked potentials using the previously reported custom Complementary and
      Alternative Medicine physiologic data collection and monitoring system, CAMAS.
      The methods used to generate visual stimuli on a PDA device and the design of an
      optical coupling device to convert the display to an electrical waveform which is
      recorded by the CAMAS base unit are presented. The optical sensor signal,
      synchronized to the visual stimulus emulates the brain's synchronized EEG signal
      input to CAMAS normally reviewed for the evoked potential response. Most
      importantly, the PDA also sends a marker message over the wireless Bluetooth
      connection to the CAMAS base unit synchronized to the visual stimulus which is
      the critical averaging reference component to obtain VEP results. Results show
      the variance in the latency of the wireless marker messaging link is consistent
      enough to support the generation and recording of visual evoked potentials. The
      averaged sensor waveforms at multiple CPU speeds are presented and demonstrate
      suitability of the Bluetooth interface for portable ambulatory visual evoked
      potential implementation on our CAMAS platform.

PMID- 21095852
TI  - A kernel-based novelty detection scheme for the ultra-fast detection of chirp
      evoked Auditory Brainstem Responses.
AB  - Auditory Brainstem Responses (ABRs) are used as objective method for diagnostics
      and quantification of hearing loss. Many methods for automatic recognition of
      ABRs have been developed, but none of them include the individual measurement
      setup in the analysis. The purpose of this work was to design a fast recognition
      scheme for chirp-evoked ABRs that is adjusted to the individual measurement
      condition using spontaneous electroencephalographic activity (SA). For the
      classification, the kernel-based novelty detection scheme used features based on
      the inter-sweep instantaneous phase synchronization as well as energy and entropy
      relations in the time-frequency domain. This method provided SA discrimination
      from stimulations above the hearing threshold with a minimum number of sweeps,
      i.e., 200 individual responses. It is concluded that the proposed paradigm,
      processing procedures and stimulation techniques improve the detection of ABRs in
      terms of the degree of objectivity, i.e., automation of procedure, and
      measurement time.

PMID- 21095853
TI  - Electric-field intrabody communication channel modeling with finite-element
      method.
AB  - Electric-field intrabody communication (EF-IBC) is a promising new scheme for the
      data exchange among wearable biomedical sensors. It uses the body as the signal
      transmission media. Compared with existing body area network (BAN) schemes, EF
      IBC can achieve higher data rate with less transmission power. Until now, the
      detailed EF-IBC channel mechanism is not well understood. In this work, finite
      element method (FEM) is utilized for the first time to investigate the EF-IBC
      channel. A circuit-coupled FEM model is established for the EF-IBC channel. The
      FEM model is extensively verified by experimental measurements. The new physical
      model enables the revelation of characteristics and effects of different
      components in the EF-IBC channel. The FEM investigation finds that the capacitive
      return path is critical to the characteristics of the EF-IBC channel. Parameters
      of the capacitive return path are quantitatively measured. The investigation also
      finds that the body plays an important role to the return path capacitance. The
      forward body path can be well modeled by a cascade of pi-shaped circuits. Based
      on the FEM model of the EF-IBC channel, a simplified circuit model is derived to
      provide an efficient tool for the transceiver design.

PMID- 21095854
TI  - The inverse problem utilizing the boundary element method for a nonstandard
      female torso.
AB  - This paper proposes a new method of rapidly deriving the transfer matrix for the
      boundary element method (BEM) forward problem from a tailored female torso
      geometry in the clinical setting. The method allows rapid calculation of
      epicardial potentials (EP) from body surface potentials (BSP). The use of EPs in
      previous studies has been shown to improve the successful detection of the life
      threatening cardiac condition--acute myocardial infarction. The MRI scanning of a
      cardiac patient in the clinical setting is not practical and other methods are
      required to accurately deduce torso geometries for calculation of the transfer
      matrix. The new method allows the noninvasive calculation of tailored torso
      geometries from a standard female torso and five measurements taken from the body
      surface of a patient. This scaling of the torso has been successfully validated
      by carrying out EP calculations on 40 scaled torsos and ten female subjects. It
      utilizes the BEM in the calculation of the transfer matrix as the BEM depends
      only upon the topology of the surfaces of the torso and the heart, the former can
      now be accurately deduced, leaving only the latter geometry as an unknown.

PMID- 21095855
TI  - Discovering functional interdependence relationship in PPI networks for protein
      complex identification.
AB  - Protein molecules interact with each other in protein complexes to perform many
      vital functions, and different computational techniques have been developed to
      identify protein complexes in protein-protein interaction (PPI) networks. These
      techniques are developed to search for subgraphs of high connectivity in PPI
      networks under the assumption that the proteins in a protein complex are highly
      interconnected. While these techniques have been shown to be quite effective, it
      is also possible that the matching rate between the protein complexes they
      discover and those that are previously determined experimentally be relatively
      low and the "false-alarm" rate can be relatively high. This is especially the
      case when the assumption of proteins in protein complexes being more highly
      interconnected be relatively invalid. To increase the matching rate and reduce
      the false-alarm rate, we have developed a technique that can work effectively
      without having to make this assumption. The name of the technique called protein
      complex identification by discovering functional interdependence (PCIFI) searches
      for protein complexes in PPI networks by taking into consideration both the
      functional interdependence relationship between protein molecules and the network
      topology of the network. The PCIFI works in several steps. The first step is to
      construct a multiple-function protein network graph by labeling each vertex with
      one or more of the molecular functions it performs. The second step is to filter
      out protein interactions between protein pairs that are not functionally
      interdependent of each other in the statistical sense. The third step is to make
      use of an information-theoretic measure to determine the strength of the
      functional interdependence between all remaining interacting protein pairs.
      Finally, the last step is to try to form protein complexes based on the measure
      of the strength of functional interdependence and the connectivity between
      proteins. For performance evaluation, PCIFI was used to identify protein
      complexes in real PPI network data and the protein complexes it found were
      matched against those that were previously known in MIPS. The results show that
      PCIFI can be an effective technique for the identification of protein complexes.
      The protein complexes it found can match more known protein complexes with a
      smaller false-alarm rate and can provide useful insights into the understanding
      of the functional interdependence relationships between proteins in protein
      complexes.

PMID- 21095856
TI  - Segmentation of liver vasculature from contrast enhanced CT images using context
      based voting.
AB  - A novel vessel context-based voting is proposed for automatic liver vasculature
      segmentation in CT images. It is able to conduct full vessel segmentation and
      recognition of multiple vasculatures effectively. The vessel context describes
      context information of a voxel related to vessel properties, such as intensity,
      saliency, direction and connectivity. Voxels are grouped to liver vasculatures
      hierarchically based on vessel context. They are first grouped locally into
      vessel branches with the advantage of a vessel junction measurement, and then
      grouped globally into vasculatures, which is implemented using a multiple feature
      point voting mechanism. The proposed method has been evaluated on 10 clinical CT
      datasets. Segmentation of third-order vessel trees from CT images (0.76 * 0.76 *
      2.0mm) of the portal venous phase takes less than 3 min on a PC with 2.0 GHz dual
      core processor and the average segmentation accuracy is up to 98%.

PMID- 21095857
TI  - Toward unsupervised adaptation of LDA for brain-computer interfaces.
AB  - There is a step of significant difficulty experienced by brain-computer interface
      (BCI) users when going from the calibration recording to the feedback
      application. This effect has been previously studied and a supervised adaptation
      solution has been proposed. In this paper, we suggest a simple unsupervised
      adaptation method of the linear discriminant analysis (LDA) classifier that
      effectively solves this problem by counteracting the harmful effect of nonclass
      related nonstationarities in electroencephalography (EEG) during BCI sessions
      performed with motor imagery tasks. For this, we first introduce three types of
      adaptation procedures and investigate them in an offline study with 19 datasets.
      Then, we select one of the proposed methods and analyze it further. The chosen
      classifier is offline tested in data from 80 healthy users and four high spinal
      cord injury patients. Finally, for the first time in BCI literature, we apply
      this unsupervised classifier in online experiments. Additionally, we show that
      its performance is significantly better than the state-of-the-art supervised
      approach.

PMID- 21095858
TI  - Point-of-care device for quantification of bilirubin in skin tissue.
AB  - Steady state diffuse reflectance spectroscopy is a nondestructive method for
      obtaining biochemical and physiological information from skin tissue. In medical
      conditions such as neonatal jaundice excess bilirubin in the blood stream
      diffuses into the surrounding tissue leading to a yellowing of the skin. Diffuse
      reflectance measurement of the skin tissue can provide real time assessment of
      the progression of a disease or a medical condition. Here we present a
      noninvasive point-of-care system that utilizes diffuse reflectance spectroscopy
      to quantifying bilirubin from skin reflectance spectra. The device consists of an
      optical system integrated with a signal processing algorithm. The device is then
      used as a platform to study two different spectral databases. The first spectral
      database is a jaundice animal model in which the jaundice reflectance spectra are
      synthesized from normal skin. The second spectral database is the spectral
      measurements collected on human volunteers to quantify the different chromophores
      and other physical properties of the tissue such as Hematocrit, Hemoglobin, etc.
      The initial trials from each of these spectral databases have laid the foundation
      to verify the performance of this bilirubin quantification device.

PMID- 21095859
TI  - Magnetoelastic materials as novel bioactive coatings for the control of cell
      adhesion.
AB  - Interfacial fibrosis is known to dramatically decrease the lifespan, stability,
      and function of biomedical implants and bone-anchored prosthetics. Bioactive
      coatings aimed at mitigating fibrous adhesions are one of the approaches to
      alleviate the problem. In this paper, we are developing a bioactive coating based
      upon a magnetoelastic (ME) material that vibrates in response to an ac magnetic
      field. In order to establish these coatings for this purpose, the ME material was
      first rendered bioactive through the sequential addition of polyurethane and
      chitosan thin films. Indirect live/dead assays were performed showing increased
      cell viability for polyurethane and chitosan-coated sensors compared to the
      uncoated controls. Direct adhesion experiments were performed to test the
      response of fibroblasts cultured on static and vibrated ME materials. Results
      showed cells adherent to static but not vibrated coatings. Detached cells showed
      no viability loss compared to controls. The finding that submicrometer ME
      vibrations can prevent cell adhesion in vitro without inducing cell death
      suggests the potential of these coatings to effectively control interfacial
      fibrosis. Future work will address the effect of vibrations on cell morphology
      and local gene expression in vitro, as well as fibrous tissue formation in vivo.

PMID- 21095860
TI  - Characterization of drug efficacy regions based on dosage and frequency
      schedules.
AB  - This paper proposes a framework to study the drug effect at the molecular level
      in order to address the following question of current interest in the drug
      community: Given a fixed total delivered drug, which is better, frequent small or
      infrequent large drug dosages? A hybrid system model is proposed to link the
      drug's pharmacokinetic and pharmacodynamic information, and allows the drug
      effects for different dosages and treatment schedules to be compared. A hybrid
      model facilitates the modeling of continuous quantitative changes that leads to
      discrete transitions. An optimal dosage-frequency regimen and the necessary and
      sufficient conditions for the drug to be effective are obtained analytically when
      the drug is designed to control a target gene. Then, we extend the analysis to
      the case where the target gene is part of a genetic regulatory network. A crucial
      observation is that there exists a "sweet spot," defined as the "drug efficacy
      region (DER)" in this paper, for certain dosage and frequency arrangements given
      the total delivered drug. This paper quantifies the therapeutic benefits of
      dosage regimen lying within the DER. Simulations are performed using
      MATLAB/SIMULINK to validate the analytical results.

PMID- 21095861
TI  - Parallel MR image reconstruction using augmented Lagrangian methods.
AB  - Magnetic resonance image (MRI) reconstruction using SENSitivity Encoding (SENSE)
      requires regularization to suppress noise and aliasing effects. Edge-preserving
      and sparsity-based regularization criteria can improve image quality, but they
      demand computation-intensive nonlinear optimization. In this paper, we present
      novel methods for regularized MRI reconstruction from undersampled sensitivity
      encoded data--SENSE-reconstruction--using the augmented Lagrangian (AL) framework
      for solving large-scale constrained optimization problems. We first formulate
      regularized SENSE-reconstruction as an unconstrained optimization task and then
      convert it to a set of (equivalent) constrained problems using variable
      splitting. We then attack these constrained versions in an AL framework using an
      alternating minimization method, leading to algorithms that can be implemented
      easily. The proposed methods are applicable to a general class of regularizers
      that includes popular edge-preserving (e.g., total-variation) and sparsity
      promoting (e.g., l(1)-norm of wavelet coefficients) criteria and combinations
      thereof. Numerical experiments with synthetic and in vivo human data illustrate
      that the proposed AL algorithms converge faster than both general-purpose
      optimization algorithms such as nonlinear conjugate gradient (NCG) and state-of
      the-art MFISTA.

PMID- 21095862
TI  - Count data modeling and classification using finite mixtures of distributions.
AB  - In this paper, we consider the problem of constructing accurate and flexible
      statistical representations for count data, which we often confront in many areas
      such as data mining, computer vision, and information retrieval. In particular,
      we analyze and compare several generative approaches widely used for count data
      clustering, namely multinomial, multinomial Dirichlet, and multinomial
      generalized Dirichlet mixture models. Moreover, we propose a clustering approach
      via a mixture model based on a composition of the Liouville family of
      distributions, from which we select the Beta-Liouville distribution, and the
      multinomial. The novel proposed model, which we call multinomial Beta-Liouville
      mixture, is optimized by deterministic annealing expectation-maximization and
      minimum description length, and strives to achieve a high accuracy of count data
      clustering and model selection. An important feature of the multinomial Beta
      Liouville mixture is that it has fewer parameters than the recently proposed
      multinomial generalized Dirichlet mixture. The performance evaluation is
      conducted through a set of extensive empirical experiments, which concern text
      and image texture modeling and classification and shape modeling, and highlights
      the merits of the proposed models and approaches.

PMID- 21095863
TI  - Mixing matrix estimation from sparse mixtures with unknown number of sources.
AB  - In blind source separation, many methods have been proposed to estimate the
      mixing matrix by exploiting sparsity. However, they often need to know the source
      number a priori, which is very inconvenient in practice. In this paper, a new
      method, namely nonlinear projection and column masking (NPCM), is proposed to
      estimate the mixing matrix. A major advantage of NPCM is that it does not need
      any knowledge of the source number. In NPCM, the objective function is based on a
      nonlinear projection and its maxima just correspond to the columns of the mixing
      matrix. Thus a column can be estimated first by locating a maximum and then
      deflated by a masking operation. This procedure is repeated until the evaluation
      of the objective function decreases to zero dramatically. Thus the mixing matrix
      and the number of sources are estimated simultaneously. Because the masking
      procedure may result in some small and useless local maxima, particle swarm
      optimization (PSO) is introduced to optimize the objective function. Feasibility
      and efficiency of PSO are also discussed. Comparative experimental results show
      the efficiency of NPCM, especially in the cases where the number of sources is
      unknown and the sources are relatively less sparse.

PMID- 21095864
TI  - Domain adaptation via transfer component analysis.
AB  - Domain adaptation allows knowledge from a source domain to be transferred to a
      different but related target domain. Intuitively, discovering a good feature
      representation across domains is crucial. In this paper, we first propose to find
      such a representation through a new learning method, transfer component analysis
      (TCA), for domain adaptation. TCA tries to learn some transfer components across
      domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In
      the subspace spanned by these transfer components, data properties are preserved
      and data distributions in different domains are close to each other. As a result,
      with the new representations in this subspace, we can apply standard machine
      learning methods to train classifiers or regression models in the source domain
      for use in the target domain. Furthermore, in order to uncover the knowledge
      hidden in the relations between the data labels from the source and target
      domains, we extend TCA in a semisupervised learning setting, which encodes label
      information into transfer components learning. We call this extension
      semisupervised TCA. The main contribution of our work is that we propose a novel
      dimensionality reduction framework for reducing the distance between domains in a
      latent space for domain adaptation. We propose both unsupervised and
      semisupervised feature extraction approaches, which can dramatically reduce the
      distance between domain distributions by projecting data onto the learned
      transfer components. Finally, our approach can handle large datasets and
      naturally lead to out-of-sample generalization. The effectiveness and efficiency
      of our approach are verified by experiments on five toy datasets and two real
      world applications: cross-domain indoor WiFi localization and cross-domain text
      classification.

PMID- 21095865
TI  - Bounded Hinfinity synchronization and state estimation for discrete time-varying
      stochastic complex networks over a finite horizon.
AB  - In this paper, new synchronization and state estimation problems are considered
      for an array of coupled discrete time-varying stochastic complex networks over a
      finite horizon. A novel concept of bounded H(infinity) synchronization is
      proposed to handle the time-varying nature of the complex networks. Such a
      concept captures the transient behavior of the time-varying complex network over
      a finite horizon, where the degree of bounded synchronization is quantified in
      terms of the H(infinity)-norm. A general sector-like nonlinear function is
      employed to describe the nonlinearities existing in the network. By utilizing a
      time-varying real-valued function and the Kronecker product, criteria are
      established that ensure the bounded H(infinity) synchronization in terms of a set
      of recursive linear matrix inequalities (RLMIs), where the RLMIs can be computed
      recursively by employing available MATLAB toolboxes. The bounded H(infinity)
      state estimation problem is then studied for the same complex network, where the
      purpose is to design a state estimator to estimate the network states through
      available output measurements such that, over a finite horizon, the dynamics of
      the estimation error is guaranteed to be bounded with a given disturbance
      attenuation level. Again, an RLMI approach is developed for the state estimation
      problem. Finally, two simulation examples are exploited to show the effectiveness
      of the results derived in this paper.

PMID- 21095866
TI  - Extended input space support vector machine.
AB  - In some applications, the probability of error of a given classifier is too high
      for its practical application, but we are allowed to gather more independent test
      samples from the same class to reduce the probability of error of the final
      decision. From the point of view of hypothesis testing, the solution is given by
      the Neyman-Pearson lemma. However, there is no equivalent result to the Neyman
      Pearson lemma when the likelihoods are unknown, and we are given a training
      dataset. In this brief, we explore two alternatives. First, we combine the soft
      (probabilistic) outputs of a given classifier to produce a consensus labeling for
      K test samples. In the second approach, we build a new classifier that directly
      computes the label for K test samples. For this second approach, we need to
      define an extended input space training set and incorporate the known symmetries
      in the classifier. This latter approach gives more accurate results, as it only
      requires an accurate classification boundary, while the former needs an accurate
      posterior probability estimate for the whole input space. We illustrate our
      results with well-known databases.

PMID- 21095867
TI  - Signature neural networks: definition and application to multidimensional sorting
      problems.
AB  - In this paper we present a self-organizing neural network paradigm that is able
      to discriminate information locally using a strategy for information coding and
      processing inspired in recent findings in living neural systems. The proposed
      neural network uses: 1) neural signatures to identify each unit in the network;
      2) local discrimination of input information during the processing; and 3) a
      multicoding mechanism for information propagation regarding the who and the what
      of the information. The local discrimination implies a distinct processing as a
      function of the neural signature recognition and a local transient memory. In the
      context of artificial neural networks none of these mechanisms has been analyzed
      in detail, and our goal is to demonstrate that they can be used to efficiently
      solve some specific problems. To illustrate the proposed paradigm, we apply it to
      the problem of multidimensional sorting, which can take advantage of the local
      information discrimination. In particular, we compare the results of this new
      approach with traditional methods to solve jigsaw puzzles and we analyze the
      situations where the new paradigm improves the performance.

PMID- 21095868
TI  - Boosting color feature selection for color face recognition.
AB  - This paper introduces the new color face recognition (FR) method that makes
      effective use of boosting learning as color-component feature selection
      framework. The proposed boosting color-component feature selection framework is
      designed for finding the best set of color-component features from various color
      spaces (or models), aiming to achieve the best FR performance for a given FR
      task. In addition, to facilitate the complementary effect of the selected color
      component features for the purpose of color FR, they are combined using the
      proposed weighted feature fusion scheme. The effectiveness of our color FR method
      has been successfully evaluated on the following five public face databases
      (DBs): CMU-PIE, Color FERET, XM2VTSDB, SCface, and FRGC 2.0. Experimental results
      show that the results of the proposed method are impressively better than the
      results of other state-of-the-art color FR methods over different FR challenges
      including highly uncontrolled illumination, moderate pose variation, and small
      resolution face images.

PMID- 21095869
TI  - JPEG2000-based scalable interactive video (JSIV).
AB  - We propose a novel paradigm for interactive video streaming and we coin the term
      JPEG2000-based scalable interactive video (JSIV) for it. JSIV utilizes JPEG2000
      to independently compress the original video sequence frames and provide for
      quality and spatial resolution scalability. To exploit interframe redundancy,
      JSIV utilizes prediction and conditional replenishment of code-blocks aided by a
      server policy that optimally selects the number of quality layer for each code
      block transmitted and a client policy that makes most of the received (distorted)
      frames. It is also possible for JSIV to employ motion compensation; however, we
      leave this topic to future work. To optimally solve the server transmission
      problem, a Lagrangian-style rate-distortion optimization procedure is employed.
      In JSIV, a wide variety of frame prediction arrangements can be employed
      including hierarchical B-frames of the scalable video coding (SVC) extension of
      the H.264/AVC standard. JSIV provides considerably better interactivity compared
      to existing schemes and can adapt immediately to interactive changes in client
      interests, such as forward or backward playback and zooming into individual
      frames. Experimental results for surveillance footage, which does not suffer from
      the absence of motion compensation, show that JSIV's performance is comparable to
      that of SVC in some usage scenarios while JSIV performs better in others.

PMID- 21095870
TI  - Geodesic active fields--a geometric framework for image registration.
AB  - In this paper we present a novel geometric framework called geodesic active
      fields for general image registration. In image registration, one looks for the
      underlying deformation field that best maps one image onto another. This is a
      classic ill-posed inverse problem, which is usually solved by adding a
      regularization term. Here, we propose a multiplicative coupling between the
      registration term and the regularization term, which turns out to be equivalent
      to embed the deformation field in a weighted minimal surface problem. Then, the
      deformation field is driven by a minimization flow toward a harmonic map
      corresponding to the solution of the registration problem. This proposed approach
      for registration shares close similarities with the well-known geodesic active
      contours model in image segmentation, where the segmentation term (the edge
      detector function) is coupled with the regularization term (the length
      functional) via multiplication as well. As a matter of fact, our proposed
      geometric model is actually the exact mathematical generalization to vector
      fields of the weighted length problem for curves and surfaces introduced by
      Caselles-Kimmel-Sapiro. The energy of the deformation field is measured with the
      Polyakov energy weighted by a suitable image distance, borrowed from standard
      registration models. We investigate three different weighting functions, the
      squared error and the approximated absolute error for monomodal images, and the
      local joint entropy for multimodal images. As compared to specialized state-of
      the-art methods tailored for specific applications, our geometric framework
      involves important contributions. Firstly, our general formulation for
      registration works on any parametrizable, smooth and differentiable surface,
      including nonflat and multiscale images. In the latter case, multiscale images
      are registered at all scales simultaneously, and the relations between space and
      scale are intrinsically being accounted for. Second, this method is, to the best
      of our knowledge, the first reparametrization invariant registration method
      introduced in the literature. Thirdly, the multiplicative coupling between the
      registration term, i.e. local image discrepancy, and the regularization term
      naturally results in a data-dependent tuning of the regularization strength.
      Finally, by choosing the metric on the deformation field one can freely
      interpolate between classic Gaussian and more interesting anisotropic, TV-like
      regularization.

PMID- 21095871
TI  - Walking motion generation, synthesis, and control for biped robot by using PGRL,
      LPI, and fuzzy logic.
AB  - This paper proposes the implementation of fuzzy motion control based on
      reinforcement learning (RL) and Lagrange polynomial interpolation (LPI) for gait
      synthesis of biped robots. First, the procedure of a walking gait is redefined
      into three states, and the parameters of this designed walking gait are
      determined. Then, the machine learning approach applied to adjusting the walking
      parameters is policy gradient RL (PGRL), which can execute real-time performance
      and directly modify the policy without calculating the dynamic function. Given a
      parameterized walking motion designed for biped robots, the PGRL algorithm
      automatically searches the set of possible parameters and finds the fastest
      possible walking motion. The reward function mainly considered is first the
      walking speed, which can be estimated from the vision system. However, the
      experiment illustrates that there are some stability problems in this kind of
      learning process. To solve these problems, the desired zero moment point
      trajectory is added to the reward function. The results show that the robot not
      only has more stable walking but also increases its walking speed after learning.
      This is more effective and attractive than manual trial-and-error tuning. LPI,
      moreover, is employed to transform the existing motions to the motion which has a
      revised angle determined by the fuzzy motion controller. Then, the biped robot
      can continuously walk in any desired direction through this fuzzy motion control.
      Finally, the fuzzy-based gait synthesis control is demonstrated by tasks and
      point- and line-target tracking. The experiments show the feasibility and
      effectiveness of gait learning with PGRL and the practicability of the proposed
      fuzzy motion control scheme.

PMID- 21095872
TI  - MAWA*-a memory-bounded anytime heuristic-search algorithm.
AB  - This paper presents a heuristic-search algorithm called Memory-bounded Anytime
      Window A* (MAWA*), which is complete, anytime, and memory bounded. MAWA* uses the
      window-bounded anytime-search methodology of AWA* as the basic framework and
      combines it with the memory-bounded A* -like approach to handle restricted memory
      situations. Simple and efficient versions of MAWA* targeted for tree search have
      also been presented. Experimental results of the sliding-tile puzzle problem and
      the traveling-salesman problem show the significant advantages of the proposed
      algorithm over existing methods.

PMID- 21095873
TI  - LMI-based stability analysis of fuzzy-model-based control systems using
      approximated polynomial membership functions.
AB  - Relaxed linear-matrix-inequality-based stability conditions for fuzzy-model-based
      control systems with imperfect premise matching are proposed. First, the
      derivative of the Lyapunov function, containing the product terms of the fuzzy
      model and fuzzy controller membership functions, is derived. Then, in the
      partitioned operating domain of the membership functions, the relations between
      the state variables and the mentioned product terms are represented by
      approximated polynomials in each subregion. Next, the stability conditions
      containing the information of all subsystems and the approximated polynomials are
      derived. In addition, the concept of the S-procedure is utilized to release the
      conservativeness caused by considering the whole operating region for
      approximated polynomials. It is shown that the well-known stability conditions
      can be special cases of the proposed stability conditions. Simulation examples
      are given to illustrate the validity of the proposed approach.

PMID- 21095875
TI  - Reconstruction of high frame rate image sequences in biomechanical related areas.
AB  - Regular video cameras shoot normally at 25/30 frames per second (fps). Actually
      there are available in the market equipments that allow us to acquire video at
      1.000.000 fps. When we observe a video sequence it becomes noticeable that great
      part of the information remains unchanged regardless of the bit rate or frame
      rate used. One origin of discontinuity in video signals is directly related to
      movement. Several areas use high frame rate images to analyze and comprehend
      certain events or effects, biomechanical engineering is one of them. Biomechanics
      engineering studies the mechanics of a living body, especially the forces exerted
      by muscles and gravity on the skeletal structure. Some examples are athlete
      assessment, were images are capture and then the acquired parameters are
      analyzed. This article describes a new methodology to decrease the space needed
      to store high frame rate image sequences in the specific case of biomechanical
      related areas.

PMID- 21095874
TI  - Intuitionistic fuzzy cognitive maps for medical decision making.
AB  - Medical decision making can be regarded as a process, combining both analytical
      cognition and intuition. It involves reasoning within complex causal models of
      multiple concepts, usually described by uncertain, imprecise, and/or incomplete
      information. Aiming to model medical decision making, we propose a novel approach
      based on cognitive maps and intuitionistic fuzzy logic. The new model, called
      intuitionistic fuzzy cognitive map (iFCM), extends the existing fuzzy cognitive
      map (FCM) by considering the expert's hesitancy in the determination of the
      causal relations between the concepts of a domain. Furthermore, a modification in
      the formulation of the new model makes it even less sensitive than the original
      model to missing input data. To validate its effectiveness, an iFCM with 34
      concepts representing fuzzy, linguistically expressed patient-specific data,
      symptoms, and multimodal measurements was constructed for pneumonia severity
      assessment. The results obtained reveal its comparative advantage over the
      respective FCM model by providing decisions that match better with the ones made
      by the experts. The generality of the proposed approach suggests its suitability
      for a variety of medical decision-making tasks.

PMID- 21095876
TI  - High resolution 3D cardiac perfusion imaging using compartment-based k-t PCA.
AB  - k-t PCA is a a regularized image reconstruction method to recover images from
      highly undersampled dynamic magnetic resonance data. It is based on the
      decomposition of the training and the undersampled data into temporally and
      spatially invariant terms using principal component analysis. In this paper, a
      compartment-based k-t PCA reconstruction approach is presented, with the
      objective of improving highly undersampled, high-resolution 3D myocardial
      perfusion magnetic resonance imaging (MRI) by constraining the temporal content
      of different spatial compartments in the image series based on the bolus arrival
      times and prior knowledge about the signal intensity-time curves.

PMID- 21095877
TI  - In-vivo clinical validation of cardiac deformation and strain measurements from
      4D ultrasound.
AB  - An important goal in clinical cardiology is the non-invasive quantification of
      regional cardiac deformation. While many methods have been proposed for the
      estimation of 3D left ventricular deformation and strains derived from 4D
      ultrasound, currently there is a lack of in vivo clinical validation of these
      algorithms on humans. In this paper, we describe the experiments used in
      validating cardiac deformation and strain estimates of 4D ultrasound using
      correlation-based optical flow tracking on two different COPD patients with
      normal left ventricular function. Validation of the algorithm was done by 1)
      validation of cardiac volume across multiple scans of the same patient and 2)
      validation of the repeatability of cardiac displacement and strain results from
      multiple scan acquisitions of the same patient. The preliminary results are
      encouraging with our algorithm producing consistent cardiac volume and strain
      results across multiple acquisitions. Furthermore, our derived 4D cardiac strains
      showed qualitatively correct results. We also observed particularly interesting
      results in the radial displacements of the posterior and lateral walls of our
      COPD patients.

PMID- 21095878
TI  - Lamb wave Shearwave dispersion ultrasound Vibrometry (SDUV) validation study.
AB  - Our group has been investigating the use of Shearwave Dispersion Ultrasound
      Vibrometry (SDUV) for quantifying viscoelasticity of the myocardium. The primary
      aim of this study is the design and testing of viscoelastic materials suitable
      for validation of the Lamb wave model in the heart. The Lamb wave SDUV method was
      used to measure shear wave velocity dispersion of gelatin and urethane rubber
      plates in the range 40-500 Hz and estimate the material properties. A finite
      element model (FEM) of a viscoelastic plate submerged in water was used to study
      the appropriateness of the Lamb wave dispersion equations. An embedded sphere
      method was used as an independent measurement of viscoelasticity. The FEM wave
      velocity dispersion data were in excellent agreement with the theoretical
      predictions. Elasticity and viscosity of urethane and gelatin obtained using the
      Lamb wave SDUV and embedded sphere methods agree within one standard deviation.

PMID- 21095879
TI  - Learning cellular texture features in microscopic cancer cell images for
      automated cell-detection.
AB  - In this paper we present a new approach for automated cell detection in single
      frames of 2D microscopic phase contrast images of cancer cells which is based on
      learning cellular texture features. The main challenge addressed in this paper is
      to deal with clusters of cells where each cell has a rather complex appearance
      composed of sub-regions with different texture features. Our approach works on
      two different levels of abstraction. First, we apply statistical learning to
      learn 6 different types of different local cellular texture features, classify
      each pixel according to them and we obtain an image partition composed of 6
      different pixel categories. Based on this partitioned image we decide in a second
      step if pre-selected seeds belong to the same cell or not. Experimental results
      show the high accuracy of the proposed method and especially average precision
      above 95%.

PMID- 21095880
TI  - 3D OCT eye movement correction based on particle filtering.
AB  - Three-dimensional optical coherence tomography (OCT) is a new ophthalmic imaging
      technique offering more detailed quantitative analysis of the retinal structure.
      Eye movement during 3D OCT scanning, however, creates significant spatial
      distortions that may adversely affect image interpretation and analysis. Current
      software solutions must use additional reference images or B-scans to correct eye
      movement in a certain direction. The proposed particle filtering algorithm is an
      independent 3D alignment approach, which does not rely on any reference image. 3D
      OCT data is considered as a dynamic system, while location of A-scan is
      represented by the state space. A particle set is generated to approximate the
      probability density of the state. The state of the system is updated frame by
      frame to detect A-scan movement. Seventy-four 3D OCT images with eye movement
      were tested and subjectively evaluated by comparing them with the original
      images. All the images were improved after z-alignment, while 81.1% images were
      improved after x-alignment. The proposed algorithm is an efficient way to align
      3D OCT volume data and correct the eye movement without using references.

PMID- 21095881
TI  - Microfabricated endoscopic probe integrated MEMS micromirror for optical
      coherence tomography bioimaging.
AB  - In this paper, we present a miniaturized endoscopic probe, consisted of MEMS
      micromirror, silicon optical bench (SiOB), grade index (GRIN) lens, single mode
      optical fiber (SMF) and transparent housing, for optical coherence tomography
      (OCT) bioimaging. Due to the use of the MEMS micromirror, the endoscopic OCT
      system is highly suitable for non-invasive imaging diagnosis of a wide variety of
      inner organs. The probe engineering and proof of concept were demonstrated by
      obtaining the two-dimensional OCT images with a cover slide and an onion used as
      standard samples and the axial resolution was around 10um.

PMID- 21095882
TI  - A uniform, raytracing-based imaging model for rigid and fiber-optic endoscopy.
AB  - Modern techniques for medical diagnosis and therapy make considerable use of
      endoscopes. Unfortunately, the wide-angle characteristic of endoscopes introduce
      severe aberrations such as chromatic aberration, geometric distortion or comb
      structure to the images. The aberrations hinder or at worst prevent the
      application of fundamental image processing techniques for an appropriate image
      analysis. In this paper, we propose a uniform ray-tracing based image model for
      rigid as well as fiber-optic endoscopes. This model enables an objective
      assessment of algorithms that rely on the image formation using physically
      correct and thus valid ground truth data.

PMID- 21095883
TI  - Identification of intracellular calcium dynamics in stimulated cardiomyocytes.
AB  - We have developed an automatic method for the analysis and identification of
      dynamical regimes in intracellular calcium patterns from confocal calcium images.
      The method allows the identification of different dynamical patterns such as
      spatially concordant and discordant alternans, irregular behavior or phase
      locking regimes such as period doubling or halving. The method can be applied to
      the analysis of different cardiac pathologies related to anomalies at the
      cellular level such as ventricular reentrant arrhythmias.

PMID- 21095884
TI  - A quadratic programming approach for the mosaicing of virtual slides that
      incorporates the positioning accuracy of the microscope stage.
AB  - We describe a novel approach for creating virtual slides that incorporates the
      positioning accuracy of the microscope stage in the optimization step. To capture
      a complete slide in microscopy, a large number of fields of view have to be
      acquired by moving the microscope stage in a controlled way. These fields of view
      are aligned in such a way that a globally consistent virtual slide is formed.
      However, depending on the positioning repeatability of the stage and the accuracy
      of the stage calibration, this results in alignment errors. These errors are
      usually resolved by applying a mosaicing algorithm. Our algorithm extends known
      mosaicing approaches by analyzing the positioning accuracy of the stage and
      incorporating this knowledge to make the mosaicing process more robust.

PMID- 21095885
TI  - Assisted navigation based on shared-control, using discrete and sparse human
      machine interfaces.
AB  - This paper presents a shared-control approach for Assistive Mobile Robots (AMR),
      which depends on the user's ability to navigate a semi-autonomous powered
      wheelchair, using a sparse and discrete human-machine interface (HMI). This
      system is primarily intended to help users with severe motor disabilities that
      prevent them to use standard human-machine interfaces. Scanning interfaces and
      Brain Computer Interfaces (BCI), characterized to provide a small set of commands
      issued sparsely, are possible HMIs. This shared-control approach is intended to
      be applied in an Assisted Navigation Training Framework (ANTF) that is used to
      train users' ability in steering a powered wheelchair in an appropriate manner,
      given the restrictions imposed by their limited motor capabilities. A shared
      controller based on user characterization, is proposed. This controller is able
      to share the information provided by the local motion planning level with the
      commands issued sparsely by the user. Simulation results of the proposed shared
      control method, are presented.

PMID- 21095886
TI  - Treadmill motor current based real-time estimation of anteroposterior force
      during gait.
AB  - We have been developing a new vehicle, "Tread-Walk 2", which supports walking for
      elderly. A control algorithm to improve the operability has been constructed. As
      the first step, we accurately estimated the user's anteroposterior force from the
      motor current value without the force sensor. This method is to develop a new
      mechanical model that considers the friction forces of the treadmill and remove
      the modeled friction losses from the output. However, we need the vertical force
      in order to develop a mechanical model. Thus, we proposed the new method to
      estimate the vertical force without the force sensor. This paper describes the
      new method to approximate the waveforms of the vertical forces as square waves by
      adding the user's weight as a parameter to the stance phase. By comparing the
      estimated anteroposterior force using the new method with the measured one using
      the force plate, the waveform pattern of the estimated one was similar with that
      of the measured one in two young subjects whose physical characteristics were
      different. This showed that the proposed method might possibly be useful for
      estimating the anteroposterior force in real-time.

PMID- 21095887
TI  - Electron influence on the reconstruction of a linac 6 MeV photon spectra by
      unfolding methods.
AB  - Megavoltage photon sources are normally used for radiotherapy treatments. For
      these equipments an accurate knowledge of their spectral distribution is
      essential for accurate dose calculations planning. There are several ways to
      determine the spectrum of a clinical photon beam: direct measurement, electron
      source modelling or reconstruction from experimental measures. In this paper we
      focus on the latter type of spectral reconstruction methods which can be used to
      provide an independent confirmation of source models for a given machine without
      any prior knowledge of the spectral distribution. This technique involves
      measuring the depth dose curve in a water phantom and applying an unfolding
      method using Monte Carlo simulated depth dose curves for consecutives mono
      energetic beams. We illustrate this theory to calculate a 6 MeV photon beam from
      an Elekta Precise radiotherapy unit using the gradient of depth dose measurements
      in a cube-shaped water tank.

PMID- 21095888
TI  - Modeling of electromagnetic stimulation of the human brain.
AB  - The World Health Organization estimates depression as a serious threat to the
      health of millions of people worldwide. The purpose of this paper is to introduce
      the ongoing research devoted to the investigation of a possibility to use low
      field electromagnetic stimulation of the human brain in the treatment of
      depressive disorder. In the course of the work the 3D models of transcranial
      magnetic stimulation and low-field magnetic stimulation based upon the use of a
      layered sphere head model have been developed. An initial approach towards the
      realistic human head reconstruction has been made. The revealed order of the
      stimulating electromagnetic field suitable for operation makes it possible to
      draft a technical specification for the stimulation device.

PMID- 21095889
TI  - Multispectral acoustic investigation of a thyroid geometrical model.
AB  - The aim of this paper is to present a new noninvasive method for investigating
      the homogeneity of the thyroid gland geometric model. The amplitude of reflected
      signal depends on the shape, size and homogeneity of the object investigated
      acoustic as well as the signal frequency emitted by generator. The eigenvalues
      proportional to the resonance frequencies are obtained by using finite element
      method applied to discretized form of differential equations of sound
      propagation. The resonance frequency variations of the first three eigenvalues
      were presented as functions of the geometrical model size and spheres with
      different radii, inside thyroid, which simulate malignant nodules.

PMID- 21095890
TI  - Predictive modeling of glucose metabolism using free-living data of type 1
      diabetic patients.
AB  - The aim of this study is to model the blood glucose metabolism of type 1 diabetic
      patients using free-living data. The proposed method considers the effect of
      diet, medication and exercise on blood glucose levels. Compartmental models are
      used to quantify the absorption of subcutaneously administered insulin, the
      absorption of glucose from the gut following a meal, as well as the effects of
      exercise on plasma glucose and insulin dynamics. Compartmental analysis is
      combined with a glucose predictive model which employs Support Vector machines
      for Regression to estimate the subcutaneous glucose concentrations. The model is
      trained and tested on real data recorded from two type 1 diabetic patients. The
      results obtained demonstrate the ability of the model to predict glucose response
      with a sufficient accuracy.

PMID- 21095891
TI  - Diagnosis of foot-and-mouth disease by electrochemical enzyme-linked immunoassay.
AB  - The development of an inmunosensor for the point-of-care detection of the foot
      and-mouth cattle disease is presented. The detector is based on an ELISA method
      with electrochemical detection. A non-structural protein, 3ABC, is used to
      selectively detect antibodies is used to selectively detect anti-3ABC antibodies
      produced after infection. The biological test is performed onto a screen printed
      electrodes. A dedicated small, portable potentiostat is employed for the control
      of the sensors, as well as data acquisition, processing, and storage.

PMID- 21095892
TI  - Smart hydrogel based microsensing platform for continuous glucose monitoring.
AB  - In this paper, we present preliminary results showing the response of glucose
      sensitive hydrogels, confined in micro-pressure sensors, to the changes in
      environmental glucose concentration. The glucose concentrations were
      incrementally varied between 20 and 0mM in 0.15M PBS solution at 7.4 pH and
      bovine serum at 7.4 pH at room temperature and response of the sensor was
      recorded. The micro sensors demonstrate a response time of 10 minutes in both PBS
      and serum. Tissue response after 55 days of subcutaneous implantation of a EtO
      sterilized sensor in mice is presented. The preliminary analysis of the
      surrounding tissue shows inflammation which is believed not to interfere with the
      sensor performance.

PMID- 21095893
TI  - LPV control of glucose for Diabetes type I.
AB  - This paper considers the problem of automatically controlling the glucose level
      in a Diabetes type I patient. Three issues have been considered: model
      uncertainty, time-varying/nonlinear phenomena and controller implementation. To
      that end, the dynamical model of the insulin/glucose relation is framed as a
      Linear Parameter Varying system and a controller is designed based on it. In
      addition, this framework allows not only a better performance than other
      classical methods, but also provides stability and performance guarantees. Design
      computations are based on convex Linear Matrix Inequality (LMI) optimization.
      Implementation is based on a low order controller whose dynamics adapts according
      to the glucose levels measured in real-time.

PMID- 21095894
TI  - Quantifying show jumping horse rider expertise using IMUs.
AB  - Horse rider ability has long been measured using horse performance, competition
      results and visual observation. Scientific methods of measuring rider ability on
      the flat are emerging such as measuring position angles and harmony of the horse
      rider system. To date no research has quantified rider ability in show jumping.
      Kinematic analysis and motion sensors have been used in sports other than show
      jumping to measure the quality of motor control patterns in humans. The aim of
      this study was to quantify rider ability in show jumping using body-mounted IMUs.
      Preliminary results indicate that there are clear differences in experienced and
      novice riders during show jumping.

PMID- 21095895
TI  - A computational model of the primary auditory neuron activity.
AB  - Sound translation into neural message at the first auditory synapse is of prime
      importance for providing organism with sound environment. Here, we compiled
      experimental features of the primary auditory neurons into a computational model,
      composed of two distinct compartments (i.e., afferent bouton and axon).
      Simulation of the model closely reproduces the whole biophysical properties of
      both excitatory post-synaptic currents and action potentials firing. This simple
      model provides a powerful tool to understand the synaptic disorders on the sound
      neural coding at the first auditory synapse.

PMID- 21095896
TI  - Quantitative analysis of tumor vascular structure after drug treatment.
AB  - This paper reports a method that aims to quantify the changes of tumour vascular
      structure as a result of drug treatment. The measures we have investigated to
      date include: vessel radii, inter-branch lengths, tortuosity and branch angles.
      We show that the distribution of vessel radii is better modelled as a gamma
      distribution as opposed to the log-normal distribution asserted by other
      researchers. We propose a new metric based on multiple linear regression to
      measure vascular tortuosity. We report statistical analyses which confirm that
      (as expected), at different significance levels, all the drugs we have tested
      (FTI, Iressa, Nelfinavir and PI-103) have positive effects in improving a
      tumour's vascular network. In each case, the changes are quantified.

PMID- 21095897
TI  - Reduction of a linear complex model for respiratory system during Airflow
      Interruption.
AB  - The paper presents methodology of a complex model reduction to its simpler
      version - an identifiable inverse model. Its main tool is a numerical procedure
      of sensitivity analysis (structural and parametric) applied to the forward linear
      equivalent designed for the conditions of interrupter experiment. Final result -
      the reduced analog for the interrupter technique is especially worth of notice as
      it fills a major gap in occlusional measurements, which typically use simple, one
      or two-element physical representations. Proposed electrical reduced circuit,
      being structural combination of resistive, inertial and elastic properties, can
      be perceived as a candidate for reliable reconstruction and quantification (in
      the time and frequency domain) of dynamical behavior of the respiratory system in
      response to a quasi-step excitation by valve closure.

PMID- 21095898
TI  - Comparison of SAR in realistic fetus models of two fetal positions exposed to
      electromagnetic wave from business portable radio close to maternal abdomen.
AB  - Since the diversification of the electromagnetic (EM) environment is spreading,
      it is essential to estimate the EM energy absorption rate [specific absorption
      rate (SAR)] of a pregnant woman's body and her fetus under various exposure
      situations. For example, if pregnant women work in jobs where they might wear
      business portable radios around their abdomens, they should also be concerned
      about this issue, because the fetuses are in their abdomens. In this paper, in
      order to evaluate the SAR in the pregnant woman and her fetus when wearing the
      wireless radio terminal on her abdomen, the SAR distribution in the fetus is
      calculated using the numerical model of the pregnant woman by exposed to near
      field of a normal mode helical antenna (NHA) with a metallic case at 150 MHz. In
      addition, the SAR in the fetus will be evaluated under two fetal positions. It
      was found that the fetal SARs are greatly affected by the distance and
      penetration path from the antenna to the fetal surface. In addition, the fetal
      SARs are lower than the RF safety guidelines for occupational exposure.

PMID- 21095899
TI  - Cardiac valve annulus manual segmentation using computer assisted visual feedback
      in three-dimensional image data.
AB  - Annulus manual segmentation is an important tool for the study of valve anatomy
      and physiology, for the four main valves of the heart (mitral, tricuspid, aortic
      and pulmonary). In this paper we review two traditional manual segmentation
      approaches: slice-by-slice and interpolating a sparse set of landmarks with a
      spline curve. We propose a new Spline Tool for the open source software platform
      Seg3D, that is fast and improves spatial coherence by providing visual feedback
      of the segmentation in real time. The Spline Tool was tested successfully on 14
      rat hearts, on all four valves.

PMID- 21095900
TI  - A control theoretic approach to venom immunotherapy with state jumps.
AB  - We investigate a model-based control method to boost the immune response. We
      apply this control method to select the appropriate immune response between the
      Th1 and Th2 responses. The idea of state jump is discussed using hybrid models
      notation. To implement the control idea we propose physically available methods.

PMID- 21095901
TI  - Modeling bacterial clearance using stochastic-differential equations.
AB  - Capillary - tissue fluid exchange is controlled by the blood pressure in the
      capillary and the osmotic pressure of blood (pressure of the tissue fluid outside
      the capillaries). In this paper, we develop a mathematical model to simulate the
      movement of bacteria into and within a capillary segment. The model is based on
      Fokker-Planck equation and Navier-Stocks equations that accounts for different
      boundary conditions. Also, we model the transportation through capillary walls by
      means of anisotropic diffusivity that depends on the pressure difference across
      the capillary walls. By solving the model with a numerical method, it was
      possible to predict the concentration of bacteria at points within the capillary.
      However, numerical analysis consumes computational time and resources. To
      efficiently simulate the bacterial clearance, we propose a segmentation model
      that is based on breaking the capillary network into smaller sections with pre
      defined properties in order to reduce the overall computational time. The
      proposed model shows a great reduction in computational time and provides
      accurate results when compared to the numerical analysis.

PMID- 21095902
TI  - Multiscale systems modeling of the tetralogy of Fallot.
AB  - This paper provides a first description of a multiscale systems modeling approach
      applied to the congenital birth defect known as the tetralogy of Fallot. The
      multiscale approach adopted owes a lot to the effort of the world-wide physiome
      consortium and the work of research groups within the European Union on the
      Virtual Physiological Human. Both a spatial scale and time scale are used to
      establish the systems boundaries of the application. The tetralogy of Fallot
      includes up to four simultaneously occurring anatomic abnormalities that underpin
      the defect. The use of finite state machines and cellular automata pave the way
      to understand the processes in time and space that contribute to the defect.

PMID- 21095903
TI  - SVM-based spectral matching for metabolite identification.
AB  - Mass spectrometry-based metabolomics is getting mature and playing an ever
      important role in the systematic understanding of biological process in
      conjunction with other members of "-omics" family. However, the identification of
      metabolites in untargeted metabolomics profiling remains a challenge. In this
      paper, we propose a support vector machine (SVM)-based spectral matching
      algorithm to combine multiple similarity measures for accurate identification of
      metabolites. We compared the performance of this approach with several existing
      spectral matching algorithms on a spectral library we constructed. The results
      demonstrate that our proposed method is very promising in identifying metabolites
      in the face of data heterogeneity caused by different experimental parameters and
      platforms.

PMID- 21095904
TI  - Shock-induced arrhythmogenesis in the human heart: A computational modelling
      study.
AB  - Electrical defibrillation by application of a strong shock to the heart is the
      only effective treatment against lethal cardiac arrhythmias such as ventricular
      fibrillation. A large body of experimental and computational research has been
      devoted to understanding shock-induced effects on the heart in an attempt to
      improve defibrillation efficacy. However, most of the research has been performed
      in small animal hearts, and in particular rabbits. The difference in size between
      rabbits and humans might limit the extrapolation of the results to the clinical
      setting. In this paper, we present, for the first time, computer simulations of
      shock-induced effects on a human ventricular model with realistic ion channel
      dynamics and fibre architecture. Bidomain simulations using the human ventricular
      model were performed using the Chaste open source simulation package. The
      parallel performance of the software package was highly improved in order to meet
      the computational requirements of these kind of studies.

PMID- 21095905
TI  - Designing antimicrobial peptides with weighted finite-state transducers.
AB  - The design of novel antimicrobial peptides (AMPs) is an important problem given
      the rise of drug-resistant bacteria. However, the large size of the sequence
      search space, combined with the time required to experimentally test or simulate
      AMPs at the molecular level makes computational approaches based on sequence
      analysis attractive. We propose a method for designing novel AMPs based on
      learning from n-gram counts of classes of amino acid residues, and then using
      weighted finite-state machines to produce sequences that incorporate those
      features that are strongly associated with AMP sequences. Finite-state machines
      are able to generate sequences that include desired n-gram features. We use this
      approach to generate candidate novel AMPs, which we test using third-party
      prediction servers. We demonstrate that our framework is capable of producing
      large numbers of novel peptide sequences that share features with known
      antimicrobial peptides.

PMID- 21095906
TI  - Evolutionary computation for the design of a stochastic switch for synthetic
      genetic circuits.
AB  - Biological systems are inherently stochastic, a fact which is often ignored when
      simulating genetic circuits. Synthetic biology aims to design genetic circuits de
      novo, and cannot therefore afford to ignore the effects of stochastic behavior.
      Since computational design tools will be essential for large-scale synthetic
      biology, it is important to develop an understanding of the role of stochasticity
      in molecular biology, and incorporate this understanding into computational tools
      for genetic circuit design. We report upon an investigation into the combination
      of evolutionary algorithms and stochastic simulation for genetic circuit design,
      to design regulatory systems based on the Bacillus subtilis sin operon.

PMID- 21095908
TI  - An expert system for hydrocephalus patient feedback.
AB  - Diagnosis of hydrocephalus symptoms and shunting system faults currently are
      based on clinical observation, monitoring of cranial growth, transfontanelle
      pressure, imaging techniques and, on occasion, studies of cerebrospinal fluid
      (CSF) dynamics. Up to date, the patient has to visit the hospital or meet
      consultant to diagnose the symptoms that occur due to rising of intracranial
      pressure or any shunt complications, which cause suffering for the patient and
      his family. This work presents the design and implementation of an expert system
      based on real-time patient feedback that aims to provide a suitable decision for
      hydrocephalus management and shunt diagnosis. Such decision would help in
      personalising the management as well as detecting and identifying of any shunt
      malfunctions without the need to contact or visit the hospital. In this paper,
      the development of patient feedback expert system is described. The outcome of
      such system would help satisfy the patient's needs regarding his/her shunt.

PMID- 21095907
TI  - Automatic decision using dirty databases: application to prostate cancer
      diagnosis.
AB  - Currently, the best way to reduce the mortality of cancer is to detect and treat
      it in its early stages. Automatic decision support systems, such as automatic
      diagnosis systems, are very helpful in this task but their performance is
      constrained by the integrity of the clinical input data. This could be a problem
      since clinical databases, in which these systems are based on, are commonly built
      up containing dirty data (empty fields, non-standard or normalized values, etc).
      This article presents a study of the performance of a clinical decision support
      system, based on an artificial neural networks, using sets of clean and dirty
      prostate cancer data. The study shows that is possible to obtain an
      implementation that allow us to avoid the problems associated to the database's
      lack of integrity and reach a similar performance using either clean or dirty
      data.

PMID- 21095909
TI  - A method for clinical and physiological event stream processing.
AB  - This paper proposes a methodology for the event stream processing of synchronous
      (physiological) and asynchronous (clinical) health data streams. The purpose is
      to illustrate the feasibility of Artemis, our extension of IBM's InfoSphere
      Streams, to appropriately deliver notifications from an initial clinical
      hypothesis within the critical care environment. We demonstrate that an positive
      alert can be delivered that is indicative of an onset of instability in
      critically ill newborns. Artemis, is also tested for its potential to allow
      clinicians the ability to interact directly with the rule-based system to prove
      certain hypothesis. We begin this methodology with a model of the clinical case
      study, and then transform that model into Stream's SPADE code. Subsequently, it
      is compiled and executed within the Streams environment to deliver notifications
      in real-time of the newborns health state.

PMID- 21095910
TI  - Fuzzy cognitive maps for medical decision support - a paradigm from obstetrics.
AB  - Medical Decision Support Systems can provide assistance in crucial clinical
      judgments, particularly for inexperienced medical professionals. Fuzzy Cognitive
      Maps (FCMs) is a soft computing technique for modeling complex systems following
      an approach similar to human reasoning and decision-making. FCMs successfully
      represent knowledge and human experience, introducing concepts to represent the
      essential elements and the cause and effect relationships among the concepts to
      model the behavior of any system. Medical Decision Systems are complex systems
      that can be decomposed to subsystems and elements, where many factors have to be
      taken into consideration that may be complementary, contradictory, and
      competitive; these factors influence each other and determine the overall
      clinical decision with varying degrees. Here a Medical Decision Support System
      based on an appropriate FCM architecture is proposed and developed, as well as a
      corresponding paradigm from obstetrics is described.

PMID- 21095911
TI  - Capacitive driven-right-leg grounding in Indirect-contact ECG measurement.
AB  - For the reduction of common-mode noise level in Indirect-contact ECG (IDC-ECG)
      measurement, a driven-right-leg grounding method was applied to the IDC-ECG.
      Because the IDC-ECG does not require any direct contact between the electrodes
      and the human skin, it is adequate for un-constraining long-term ECG measurement
      at home and its various applications are now under development. However, larger
      60 Hz noise induced by power line appears in IDC-ECG than in conventional ECG,
      that is a restriction of IDC-ECG application. In this study, the driven-right-leg
      ground which has been used in conventional direct-contact ECG, was adapted to the
      IDC-ECG measurement, by feedback of the inversion of amplified common-mode noise
      to the body through the conductive textile laid on the chair seat. It was shown
      that the level of 60Hz power line noise was reduced to about -40 dB when the
      driven-right-leg gain was 1000.

PMID- 21095912
TI  - Optimized surgical tool for pectus bar extraction.
AB  - Surgeons on a daily basis improve or rescue human lives. Therefore, they should
      be provided with the most optimal tools so their skills are fully utilized. In
      this paper, we present such an optimized tool for surgeons who employ the Nuss
      procedure to correct pectus excavatum - a congenital chest wall deformity. The
      Nuss procedure is a minimally invasive procedure that results in the placement of
      a metal bar inside the chest cavity. The bar is removed after approximately two
      years. Surgeons have been reporting that the currently available tools for the
      bar extraction do not provide the most optimal functionality. Therefore, we have
      proposed an optimized and improved design of the tool for the bar extraction. The
      improved design tool is further analyzed using finite element techniques.
      Additionally, we have built a physical prototype to ensure that the new tool to
      seamlessly integrate with the bar and to further evaluate by the surgeons who
      routinely practice the Nuss procedure. In order to validate in the future the
      final design, we have manufactured wax models that will serve as the patterns in
      the casting process of metal prototypes. They should provide enough strength to
      withstand stresses present in the bar straightening process.

PMID- 21095913
TI  - Acupoint stimulation device using focused ultrasound.
AB  - Acupuncture is used widely in oriental medicine. But it is difficult to stimulate
      continuously or intermittently in daily life with conventional acupuncture. An
      acupoint stimulation device using focused ultrasound has been developed. Because
      the device size is about 6 mm in diameter, it can be easily put on the skin
      during daily life. Appropriate stimulation intensity and pattern can be chosen by
      changing driving voltage and pattern. In this paper, we stimulated acupoints with
      this device and measured the blood flow volume of brachial artery. As a result,
      the blood flow volume increased significantly as well as acupuncture. Because the
      device stimulate acupoints with intactness of skin, advantages of this device is
      free from infection and fear and pain by insertion of acupuncture needles.

PMID- 21095914
TI  - Effectiveness of Laser treatment at acupuncture sites compared to traditional
      acupuncture in the treatment of peripheral artery disease.
AB  - Cardiovascular diseases are the main causes of mortality, not only in Brazil, but
      around the world. The use of acupuncture as a complementary and alternative
      treatment for cardiovascular diseases has been suggested for animals as well as
      human beings. Possible advantages in using acupuncture are the low cost of
      treatment and low risks of collateral damage from a combination of acupuncture
      with other medical treatments. The purpose of this study is to assess the effect
      of traditional acupuncture with needles and laser acupuncture on arterial
      pressure and peripheral circulation of inferior limbs in patients with
      circulatory deficiency. Ten acupuncture points were stimulated in 40 individuals,
      being that 20 were stimulated by Aluminum gallium arsenide (AlGaAs) laser with
      emission in the red spectral region (650 nm) using an energy density of 2,4
      J/cm2, and 20 were stimulated by systemic acupuncture needles. The analysis of
      peripheral circulation was performed based on the measurement of arterial
      pressure of the ankle and arms, using sphygmomanometer and Doppler equipment. The
      variance of the revascularization index of the laser acupuncture group was 0,057,
      and 0.030 for the needles group with p= 0,006. These results show that only those
      treated with laser acupuncture exhibit a significant increase in systolic
      pressure of their lower limbs, with a consequent improvement of the
      Revascularization Index, suggesting that different stimuli on acupuncture points
      generate different variations of peripheral resistance of lower limbs. is column.

PMID- 21095915
TI  - Multi-organ effects of Conducted Electrical Weapons (CEW) -- a review.
AB  - Since the introduction of the Conducted Electrical Weapons (CEW) several studies
      have been conducted and multiple reports have been published on safety of these
      devices from a medical point of view. Use of these devices in different
      situations and reported deaths attracts media attention and causes general
      anxiety around these devices. These devices have several limitations- such as
      rate of fire or maximum effective range in comparison to fire arms. Here we wish
      to review medical publications regarding the safety of these devices based on
      different systems.

PMID- 21095916
TI  - Hiding robot inertia using resonance.
AB  - To enable compliant training modes with a rehabilitation robot, an important
      prerequisite is that any undesired human-robot interaction forces caused by robot
      dynamics must be avoided, either by an appropriate mechanical design or by
      compensating control strategies. Our recently proposed control scheme of
      "Generalized Elasticities" employs potential fields to compensate for robot
      dynamics, including inertia, beyond what can be done using closed-loop force
      control. In this paper, we give a simple mechanical equivalent using the example
      of the gait rehabilitation robot Lokomat. The robot consists of an exoskeleton
      that is attached to a frame around the patient's pelvis. This frame is suspended
      by a springloaded parallelogram structure. The mechanism allows vertical
      displacement while providing almost constant robot gravity compensation. However,
      inertia of the device when the patient's pelvis moves up and down remains a
      source of large interaction forces, which are reflected in increased ground
      reaction forces. Here, we investigate an alternative suspension: To hide not only
      gravity, but also robot inertia during vertical pelvis motion, we suspend the
      robot frame by a stiff linear spring that allows the robot to oscillate
      vertically at an eigenfrequency close to the natural gait frequency. This
      mechanism reduces human-robot interaction forces, which is demonstrated in pilot
      experimental results.

PMID- 21095917
TI  - A novel variable stiffness actuator: minimizing the energy requirements for the
      stiffness regulation.
AB  - The design of robots required to work in the close vicinity or physically
      interact with humans such as humanoids machines, rehabilitation or human
      performance augmentation systems should not follow the traditional design rule
      'stiffer is better'. Safety is a particularly vital concern in these systems and
      to maximize it a different design approach should be used. The role of compliance
      in improving specific suspects of the robotic system, including safety and energy
      efficiency, has been studied and validated in many works. This work presents the
      design and realization of a new variable compliance actuator for robots
      physically interacting with humans, e.g. prosthesis devices and exoskeleton
      augmentation systems. The actuator can independently control the equilibrium
      position and stiffness using two motors. The main novelty of the proposed
      variable stiffness actuator is that the stiffness regulation is achieved not
      through the pretension of the elastic elements which needs the stiffness tuning
      actuator to act against the forces generated by the springs but by mechanically
      adjusting the fixation of the spring elements. As a result the stiffness actuator
      does not need to act against the spring forces reducing the energy required for
      the stiffness adjustment to minimal.

PMID- 21095918
TI  - Soft artificial tactile sensors for the measurement of human-robot interaction in
      the rehabilitation of the lower limb.
AB  - A new and alternative method to measure the interaction force between the user
      and a lower-limb gait rehabilitation exoskeleton is presented. Instead of using a
      load cell to measure the resulting interaction force, we propose a distributed
      measure of the normal interaction pressure over the whole contact area between
      the user and the machine. To obtain this measurement, a soft silicone tactile
      sensor is inserted between the limb and commonly used connection cuffs. The
      advantage of this approach is that it allows for a distributed measure of the
      interaction pressure, which could be useful for rehabilitation therapy assessment
      purposes, or for control. Moreover, the proposed solution does not change the
      comfort of the interaction; can be applied to connection cuffs of different
      shapes and sizes; and can be manufactured at a low cost. Preliminary results
      during gait assistance tasks show that this approach can precisely detect changes
      in the pressure distribution during a gait cycle.

PMID- 21095920
TI  - On the control of the MIT-skywalker.
AB  - Walking impairments are a common sequela of neurological injury, severely
      affecting the quality of life of both adults and children. Gait therapy is the
      traditional approach to ameliorate the problem by re-training the nervous system
      and there have been some attempts to mechanize such approach. In this paper, we
      present a novel device to deliver gait therapy, which, in contrast to previous
      approaches, takes advantage of the concept of passive walkers and the natural
      dynamics of the lower extremity in order to deliver more "ecological" therapy. We
      also discuss the closed-loop control scheme, which enables safe and efficient
      operation of the device, and present the initial feasibility tests with
      unimpaired subjects.

PMID- 21095919
TI  - A wearable ergonomic gaze-tracker for infants.
AB  - In this paper we present a low-cost hardware and software solution for monitoring
      gaze and head movements in infants. The proposed device consists in a webcam and
      a magneto-inertial sensor mounted on a cap. Signal acquisition and elaboration is
      carried out on a common PC. Technological choices and calibration procedures rely
      on a minimally obtrusive and ecological approach. The purpose of this work is to
      present preliminary in-lab evaluations on a new method that may enable
      researchers to gain new insights on the contents of visual experience from the
      child's point of view.

PMID- 21095921
TI  - Human characterization and emotion characterization from gait.
AB  - Human gait has been proven to be of importance when trying to recognize people.
      In addition gait also conveys the emotional state of someone. The present study
      propose to objectively and systematically analyze gait data to highlight features
      that can characterize someone and the emotion conveyed. Rather than using gait
      stance phase, frequency, footstep length... we use the inverse kinematics data
      computed from the motion-capture data using a 34 degree of freedom human body
      model. Then we compute a similarity criteria with respect to a reference motion.
      We first utilize the 6 components of the base-link velocity for the similarity
      criteria computation. The motion data are collected on 4 candidates (2 males and
      2 females professional actors), 4 emotional states are simulated: neutral, happy,
      angry, sad. Each is repeated 5 times. The experimental results show that using
      the gait characteristics it is possible to characterize each candidate and to
      characterize each emotional state with a good accuracy.

PMID- 21095922
TI  - Adaptive estimation of temporal gait parameters using body-worn gyroscopes.
AB  - Body-worn kinematic sensors have been widely proposed for use in portable, low
      cost, ambulatory monitoring of gait. Such sensor based systems could avoid the
      need for high-cost laboratory-based methods for measurement of gait. We aimed to
      evaluate an adaptive gyroscope-based algorithm for automated temporal gait
      analysis using body-worn wireless gyroscopes. Temporal gait parameters were
      calculated from initial contact (IC) and terminal contact (TC) points derived
      from gyroscopes, contained in wireless sensors on the left and right shanks,
      using a newly developed adaptive algorithm. Gyroscope data from nine healthy
      adult subjects performing four walks at three different speeds were then compared
      against data acquired simultaneously using two force-plates. Results show that
      the mean true error between the adaptive gyroscope algorithm and force-plate was 
      5.5 +/- 7.3 ms and 40.6 +/- 19.2 ms for IC and TC points respectively; the latter
      representing a consistent, systematic error of this magnitude that may be
      intrinsic to shank-mounted gyroscopes. These results suggest that the algorithm
      reported here could form the basis of a robust, portable, low-cost system for
      ambulatory monitoring of gait.

PMID- 21095923
TI  - A single gyroscope method for spatial gait analysis.
AB  - Inertial sensors have become increasingly popular in gait analysis, due to their
      highly portable, low cost, and potentially wireless nature. However, accurate
      spatial gait analysis using few sensors remains a challenge. A gyroscope-based
      algorithm for spatial gait analysis is presented. This novel algorithm (SGA) uses
      data from a single gyroscope attached to each shank. The performance of the SGA
      was compared to that of an electronic walkway, GAITRite(r). The two systems
      compared favorably, with a mean error in stride length of 0.09 +/- 0.07 m, and a
      mean error in stride velocity of 0.11 +/- 0.10 m/s. The error between the SGA and
      GAITRite was also similar to that reported by previous inertial sensor based
      algorithms. The relationship between stride length and stride velocity, as well
      as that of subject height and stride length was also examined. This new method
      provides an inexpensive, portable system for spatial or spatio-temporal gait
      analysis, which has potential for use in any location.

PMID- 21095924
TI  - A PDF-based classification of gait cadence patterns in patients with amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a type of neurological disease due to the
      degeneration of motor neurons. During the course of such a progressive disease,
      it would be difficult for ALS patients to regulate normal locomotion, so that the
      gait stability becomes perturbed. This paper presents a pilot statistical study
      on the gait cadence (or stride interval) in ALS, based on the statistical
      analysis method. The probability density functions (PDFs) of stride interval were
      first estimated with the nonparametric Parzen-window method. We computed the mean
      of the left-foot stride interval and the modified Kullback-Leibler divergence
      (MKLD) from the PDFs estimated. The analysis results suggested that both of these
      two statistical parameters were significantly altered in ALS, and the least
      squares support vector machine (LS-SVM) may effectively distinguish the stride
      patterns between the ALS patients and healthy controls, with an accurate rate of
      82.8% and an area of 0.87 under the receiver operating characteristic curve.

PMID- 21095925
TI  - Domo-Grip: functional evaluation and rehabilitation using grip force.
AB  - Grip force measurement is routinely used to identify pathologies, evaluate
      muscular function, and as part of rehabilitation. Grip force has also been shown
      to be a good indicator of the capacity of elderly to live independently owing to
      its strong relationship with clinical tests such as the Index of Activities of
      Daily Living. An autonomous, communicant grip-force measurement device is
      presented in this paper in order to perform grip-force evaluation at home. The
      Domo-Grip system consists of the Grip-Ball, the Grip-Box, and Grip-Soft. The Grip
      Ball measures the pressure resulting from grip force, the Grip-Box serves as the
      communication hub, while Grip-Soft is an interactive software suite. The Domo
      Grip system can be used as part of a home-based rehabilitation, and also for
      functional evaluation as part of an assessment of the capacity of elderly to live
      autonomously.

PMID- 21095926
TI  - Extension assist control for individuals with cervical cord injury using motion
      assist robot for upper limb.
AB  - Many people of all ages have sustained cervical cord injury in traffic accidents
      or sport accidents, and consequently suffered physical impairment. Among these
      individuals dysfunction of the upper limbs is a concern, although recovery from
      dysfunction is possible through rehabilitation. In this study, we developed an
      assistive robot for upper limb movement which has high effectiveness in
      rehabilitation. To achieve this, we devised an algorithm of a dynamic filter that
      decreases the noise and delay of the device for controlling the motion assist
      robot stably. This filter changes the cutoff frequency depending on the amount of
      input change. The robot assists movement only during elbow extension. The
      effectiveness of the proposed method is demonstrated through experiments.

PMID- 21095927
TI  - Towards smart prosthetic hand: Adaptive probability based skeletan muscle fatigue
      model.
AB  - Skeletal muscle force can be estimated using surface electromyographic (sEMG)
      signals. Usually, the surface location for the sensors is near the respective
      muscle motor unit points. Skeletal muscles generate a spatial EMG signal, which
      causes cross talk between different sEMG signal sensors. In this study, an array
      of three sEMG sensors is used to capture the information of muscle dynamics in
      terms of sEMG signals. The recorded sEMG signals are filtered utilizing optimized
      nonlinear Half-Gaussian Bayesian filters parameters, and the muscle force signal
      using a Chebyshev type-II filter. The filter optimization is accomplished using
      Genetic Algorithms. Three discrete time state-space muscle fatigue models are
      obtained using system identification and modal transformation for three sets of
      sensors for single motor unit. The outputs of these three muscle fatigue models
      are fused with a probabilistic Kullback Information Criterion (KIC) for model
      selection. The final fused output is estimated with an adaptive probability of
      KIC, which provides improved force estimates.

PMID- 21095928
TI  - Experimental analysis for the contribution of tooth vibration to production of
      sibilant /s/ ~ measurement of sound and vibration ~.
AB  - Sibilant /s/, one of unvoiced sounds, is believed to be produced by flow
      turbulence provoked by the impingement of a jet to anterior teeth. Although it
      would be possible that the impingement of a jet as well as pressure fluctuations
      behind the anterior teeth associated with flow turbulence make anterior teeth
      vibrate, whereby contributing to the production of sibilant /s/, no studies have
      focused on this aspect. The present study is designed to investigate the
      possibility that the vibration of teeth contributes to the production of sibilant
      /s/. A morphologically simplified model of an oral cavity is fabricated. An air
      is steadily delivered at 45 L/min to the model to produce aeroacoustic sounds.
      Sound and vibration of teeth (obstacle wall) are measured simultaneously with a
      microphone and the Michelson interferometer. The spectrum analysis showed two
      peaks in the sound at 1,300 and 3,500 Hz, and one peak in the wall vibration at
      3,500 Hz. An association of the peak at 3,500 Hz between the sound and wall
      vibration suggested that this sound is produced as a result of wall vibration.
      Experiments exhibited a decrease in the sound amplitude with an increase in
      thickness (rigidity) of teeth (obstacle wall). Those results demonstrated
      potential of the proposed method for exploring the production mechanism of
      sibilant /s/ and possibility of the contribution of teeth vibration to the
      production of sibilant /s/.

PMID- 21095929
TI  - Post-prandial plasma glucose prediction in type I diabetes based on Impulse
      Response Models.
AB  - In this paper the impact of different meals and rapid insulin were estimated as
      Finite Impulse Response Models from a data set of 18 patients. Based on these
      models short-term individualized predictors were tested for 20 and 60 minute
      prediction. The predictors were evaluated using Clarke Grid Analysis and had on
      average more than 94 % and 75 % in the A zone and less than 1 % and 3 % in the
      errorous C/D/E zones, which in comparison to other published results is
      competitive.

PMID- 21095930
TI  - Dynamic modeling of EMG-force relationship using parallel cascade identification.
AB  - Parallel cascade identification (PCI) is used as a dynamic estimation tool to map
      surface electromyography recordings from upper-arm muscles to the elbow-induced
      force at the wrist. PCI mapping is composed of parallel connection of a cascade
      of linear dynamic and nonlinear static blocks. Experimental comparison between
      PCI and previously published orthogonalization scheme has shown superior force
      prediction by PCI. The improved performance is attributed to the structural
      capability of PCI in capturing nonlinear dynamic effects in the generated force.

PMID- 21095931
TI  - Phase velocity analysis of acoustic propagation in trabecular bone.
AB  - The trabecular bones are highly dispersive acoustic media composed by randomly
      shaped trabeculae (considered as scatterers) and surrounded by bone marrow. An
      acoustic wave generated by an incident ultrasonic pulse with respect to the media
      under study, shows that its velocity and amplitude are a function of the density
      size and shaped of the scatterers. Two different methods were used to
      theoretically study this scattering phenomena: i) a self-consistent model
      proposed by Sabina and Willis, and ii) the multiple-scattering theory of Waterman
      Truell. These methods were able to compute the phase velocity and amplitude as a
      function of operating frequency, density and size of scatterers. The theoretical
      results were compared with experimental data already published and the phase
      veloctiy shows a good agreement for low concentration of scatterers.

PMID- 21095932
TI  - Monitoring of drowsiness and microsleep.
AB  - An overview is presented of different studies on monitoring and detection of
      drowsiness and microsleep (MS) during driving simulation.

PMID- 21095933
TI  - Lapses of responsiveness: Characteristics, detection, and underlying mechanisms.
AB  - Lapses in responsiveness ('lapses'), particularly microsleeps and attention
      lapses, are complete disruptions in performance from approximately 0.5-15 s. They
      are of particular importance in the transport sector in which there is a need to
      maintain sustained attention for extended periods and in which lapses can lead to
      multiple-fatality accidents.

PMID- 21095934
TI  - Arousing feedback rectifies lapse in performance and corresponding EEG power
      spectrum.
AB  - This study explores electroencephalographic (EEG) dynamics and behavioral changes
      in response to arousing auditory signals presented to individuals experiencing
      momentary cognitive lapses. Arousing auditory feedback was delivered to the
      subjects in half of the non-responded lane-deviation events during a sustained
      attention driving task, which immediately agitated subject's responses to the
      events. The improved behavioral performance was accompanied by concurrent power
      suppression in the theta- and alpha-bands in the lateral occipital cortices. This
      study further explores the feasibility of estimating the efficacy of arousing
      feedback presented to the drowsy subjects by monitoring the changes in EEG power
      spectra.

PMID- 21095935
TI  - A transparent electrode array for simultaneous cortical potential recording and
      intrinsic signal optical imaging.
AB  - Intrinsic signal optical imaging (ISOI) is a technique that enables researchers
      to relate changes in cortical activity in response to stimuli by measuring
      changes in hemoglobin oxygenation and local blood volume. As the time course of
      these changes - local blood volume in particular - is of the order of seconds,
      the neural activity that initiates these changes is only indirectly acquired in
      ISOI. To better correlate these events, it is beneficial to simultaneously record
      both the evoked cortical potentials and ISOI. In this study we present a novel,
      transparent, recording array that allows the combination of optical imaging with
      electrical recordings without the use of metal electrodes in the observation
      field. Pilot data were recorded after visual and electrical stimuli of the eye to
      prove the concept.

PMID- 21095936
TI  - Intrafascicular thin-film multichannel electrodes for sensory feedback: Evidences
      on a human amputee.
AB  - The performance of motor neuroprostheses or robotic arm prostheses can be
      significantly improved by delivering sensory feed-back related to the ongoing
      motor task (e.g. the slippage of an object during grasping). Microfabricated
      neural electrodes implantable in peripheral nervous system seem a promising
      approach to this aim. New generation of thin-film intrafascicular electrodes
      longitudinally implantable in peripheral nerves (tf-LIFE4) has been developed and
      tested for afferent stimulation in human amputee case study.

PMID- 21095937
TI  - A modular 256-channel micro electrode array platform for in vitro and in vivo
      neural stimulation and recording: BioMEA.
AB  - In order to understand the dynamics of large neural networks, where information
      is widely distributed over thousands of cells, one of today's challenges is to
      successfully monitor the simultaneous activity of as many neurons as possible.
      This is made possible by using the Micro-Electrode Array (MEA) technology
      allowing neural cell culture and/or tissue slice experimentation in vitro. Thanks
      to development of microelectronics' technologies, a novel data acquisition system
      based on MEA technology has been developed, the BioMEATM. It combines the most
      advanced MEA biochips with integrated electronics, and a novel user-friendly
      software interface. To move from prototype (result of the RMNT research project
      NEUROCOM) to manufactured product, a number of changes have been made. Here, we
      present a 256-channel MEA data acquisition system with integrated electronics
      (BioMEATM) allowing simultaneous recording and stimulation of neural networks for
      in vitro and in vivo applications. This integration is a first step towards an
      implantable device for BCI (Brain Computer Interface) studies and neural
      prosthesis.

PMID- 21095938
TI  - 3D microprobes for deep brain stimulation and recording.
AB  - A new generation of three dimensional (3D) multi channel microprobes is reported
      for deep brain stimulation (DBS) applications offering both stimulation and
      recording capabilities. The devices are comprised of planar flexible microprobes
      assembled or folded over cylindrical polyurethane shafts with radiuses as low as
      350 microm. As a direct benefit of this approach, the dimensions and density of
      the electrode sites are precisely defined by the sub-micrometer resolution of the
      lithography processes employed for fabrication of planar devices. This work
      presents a microprobe with 16 stimulating and 16 recording channels. The
      stimulation sites are 100 microm * 1.5 mm while the recording sites are 20 microm
      * 20 microm.

PMID- 21095939
TI  - Tuning electrode impedance for the electrical recording of biopotentials.
AB  - Tuning the electrode impedance through the DC biasing of iridium oxide is
      presented. Impedance reduction of up to two orders of magnitude was reproducibly
      observed in 20 microm diameter microelectrodes at a biasing of 1V.

PMID- 21095940
TI  - An implantable integrated low-power amplifier-microelectrode array for Brain
      Machine Interfaces.
AB  - One of the important challenges in designing Brain-Machine Interfaces (BMI) is to
      build implantable systems that have the ability to reliably process the activity
      of large ensembles of cortical neurons. In this paper, we report the design,
      fabrication, and testing of a polyimide-based microelectrode array integrated
      with a low-power amplifier as part of the Florida Wireless Integrated Recording
      Electrode (FWIRE) project at the University of Florida developing a fully
      implantable neural recording system for BMI applications. The electrode array was
      fabricated using planar micromachining MEMS processes and hybrid packaged with
      the amplifier die using a flip-chip bonding technique. The system was tested both
      on bench and in-vivo. Acute and chronic neural recordings were obtained from a
      rodent for a period of 42 days. The electrode-amplifier performance was analyzed
      over the chronic recording period with the observation of a noise floor of 4.5
      microVrms, and an average signal-to-noise ratio of 3.8.

PMID- 21095941
TI  - Predicting a protein's melting temperature from its amino acid sequence.
AB  - Melting temperature is an important characteristic feature of a protein and is
      used for various purposes such as in drug development. Currently protein melting
      temperature is determined by laboratory methods such as Differential Scanning
      Calorimetry, Circular Dichroism, Fourier transform infrared spectroscopy and
      several other methods. These methods are laborious and costly. Therefore, we
      propose a novel bioinformatics based method for predicting protein melting
      temperature from amino acid sequence of a protein. This is not only a challenging
      task but has been previously unexplored. For this study, melting temperature of
      230 proteins from a range of organisms was collected along with their sequence
      information from the published literature. The melting temperature of these
      proteins represents a very large spectrum and varies between 25 degrees C and 113
      degrees C. The protein sequences are then used to derive two sets of sequence
      driven features, namely amino acid composition (AAC) and pseudo-amino acid
      composition (PseudoAAC) to characterise the proteins. In order to predict the
      melting temperature, two different computational intelligence methods, namely
      artificial neural networks (ANN) and adaptive network-fuzzy inference system
      (ANFIS) were utilized. Amongst over 100 different models generated, the ANN
      produced the best model with the least error (0.01087 for the AAC and 0.01086 for
      the pseudoAAC). As both feature sets yielded quite similar error and computation
      of pseudoAAC is costly when compared to that of AAC, traditional AAC seems to be
      an effective feature set for predicting melting temperature. The results obtained
      in this study are very promising and, for the first time, shows that the melting
      temperature of a protein can be predicted from its amino acid sequence only.
      Therefore, costly lab-based experiments may not be required to measure the
      melting temperature and the bioinformatics models can help speed up laboratory
      processes such as in drug development.

PMID- 21095942
TI  - Stress development, heat production and dynamic modulus of rat isolated cardiac
      trabeculae revealed in a flow-through micro-mechano-calorimeter.
AB  - Progress toward understanding the thermo-mechanical behavior of isolated cardiac
      muscle, excised from either healthy or diseased heart, is contingent on being
      able to measure simultaneously the stress (force per cross-sectional area) and
      heat production. Determination of dynamic modulus (dynamic stiffness times muscle
      length per cross-sectional area) sheds further light on the behavior of the force
      and heat-generating actin-myosin cross-bridges. We are in a unique position to
      perform such measurements, given the recent completion of a micro-mechano
      calorimeter. In this paper, we characterize the micro-mechano-calorimeter and
      present experimental results of twitch stress, heat per twitch and dynamic
      modulus measured in rat right-ventricular trabeculae at varied stimulus
      frequencies and muscle lengths. The minute radial dimensions of cardiac
      trabeculae (which approximate those of a human hair) ensure adequate provision of
      oxygen and nutrients via diffusion from the continuously replenished superfusate
      flowing through the measurement chamber. This enables investigation of the thermo
      mechanical performance of cardiac trabeculae for many hours.

PMID- 21095943
TI  - Feasibility study of a smart pen for autonomous detection of concentration lapses
      during reading.
AB  - We implemented a portable smart pen system capable of detecting lapses in
      concentration during reading. An accelerometer and a microcontroller are embedded
      within a pen casing to record data as a user reads sections of text using the pen
      as a pointer. When a substantial pause in reading is detected, the system
      generates an appropriate warning or alarm. An accompanying software program can
      communicate with the pen through a USB interface to customize system parameters,
      record relevant data, and graph collected data over time. The overall
      effectiveness of a prototype system was tested on 11 normal volunteers and 3
      persons with attention deficit disorder (ADD). The prototype system had
      probability of false alarm of 19%, and sensitivity of 82%. With further
      refinement, this system could enable patients with attention
      deficit/hyperactivity disorder maintain concentration during reading in a variety
      of environments.

PMID- 21095944
TI  - Modeling the motor striatum under Deep Brain Stimulation in normal and MPTP
      conditions.
AB  - Striatum (STR) is the major input stage of the basal ganglia (BG). It combines
      information from cortex, subthalamic nucleus (STN) and external globus pallidus
      (GPe), and projects to the output stages of the BG, where selection between
      concurrent motor programs is performed. Parkinson's disease (PD) reduces the
      concentration of dopamine (DA, a neurotransmitter) in STR and changes in the
      level of DA correlate with the onset of PD motor disorders. Though STR plays a
      pivotal role in BG, its behavior under PD and Deep Brain Stimulation (DBS) is
      still unclear. We develop point-process models of the STR neurons as a function
      of the activity in GPe, cortex, and DBS. We use single unit recordings from a
      monkey under STN DBS at different frequencies before and after treatment with 1
      methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to develop PD motor symptoms.
      The models suggest that STR neurons have prominent bursting activity in normal
      conditions, positive correlation with cortex (3-10 ms delay), and mild negative
      correlation with GPe (1-5 ms lag). DA depletion evokes 30-60 Hz oscillations, and
      increases the propensity of each neuron to be inhibited by surrounding neurons.
      DBS elicits antidromical activation, masks existent dynamics, reinforces
      dependencies between nuclei, and entrains at the stimulation frequency in both
      conditions.

PMID- 21095945
TI  - A computational model of direct brain stimulation by electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) is the most effective treatment for severe
      depressive disorder, and yet the mechanisms of its therapeutic effects remain
      largely unknown. A novel computational model is presented in this study to
      simulate and investigate direct cortical excitation caused by bitemporal
      electroconvulsive therapy (BT ECT), using a finite element model (FEM) of the
      human head. The skull was modeled with anisotropic conductivity, with an
      excitable ionic neural model incorporated into the brain based on the classic
      Hodgkin-Huxley formulation. Results suggested that this model is able to
      reproduce direct stimulation of the cortex during the application of ECT.

PMID- 21095946
TI  - Modeling the electric field induced in a high resolution realistic head model
      during transcranial current stimulation.
AB  - Much of our knowledge about the electric field distribution in transcranial
      current stimulation (tCS) still relies on results obtained from layered spherical
      head models. In this work we created a high resolution finite element model of a
      human head by segmentation of MRI images, and paid particular attention to the
      representation of the cortical sheet. This model was then used to calculate the
      electric field induced by two electrodes: an anode placed above the left motor
      cortex, and a cathode placed over the right eyebrow. The results showed that the
      maxima of the current density appear located on localized hotspots in the bottom
      of sulci and not on the cortical surface as would be expected from spherical
      models. This also applies to the components of the current density normal and
      tangential to the cortical surface. These results show that such highly detailed
      head models are needed to correctly predict the effects of tCS on cortical
      neurons.

PMID- 21095947
TI  - A continuum model of the retinal network and its response to electrical
      stimulation.
AB  - A continuum network model of the retina is presented, consisting of an active
      implementation of the retinal ganglion cell tissue layer and passive
      implementation of deeper cell layers. The retinal ganglion cell layer receives
      excitatory presynaptic inputs from the bipolar layer and inhibitory presynaptic
      inputs from the amacrine layer. Simulations were performed to investigate the
      behavior of retinal tissue activation with epiretinal and suprachoroidal
      electrode stimulation. The results indicated the presence of both early and late
      onset action potentials consistent with experimental findings.

PMID- 21095948
TI  - Modeling the effects of Deep Brain Stimulation on sensorimotor cortex in normal
      and MPTP conditions.
AB  - Deep Brain Stimulation (DBS) is an effective surgical therapy for the treatment
      of movement disorders in Parkinson's disease (PD) and other neurological
      pathologies. DBS is known to modulate the spiking activity of the neurons within
      the basal ganglia, but how such modulation impacts the primary sensorimotor
      cortex is still uncertain. In this study a monkey was stimulated with DBS at
      several frequencies in the subthalamic nucleus (STN) before and after treatment
      with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to develop PD symptoms,
      while single unit recordings are simultaneously obtained from the sensorimotor
      cortex. We exploit such data to develop point-process input-output models of the
      cortical neurons. Our models describe the effects of stimulation in normal and
      MPTP conditions and investigate the influence of the stimulation frequency on the
      neuronal activity. Our models show increased synchronization of the cortical
      neurons in MPTP vs. normal conditions before stimulation, suggest that STN DBS
      impacts the cortical activity by antidromically eliciting spikes at the
      stimulation frequency, and support the hypothesis that high frequency DBS
      partially masks the effects of thalamo-cortical input.

PMID- 21095949
TI  - Vibrotactile guidance for trajectory following in computer aided surgery.
AB  - Most conventional computer-aided navigation systems assist the surgeon visually
      by tracking the position of an ancillary and by superposing this position into
      the 3D preoperative imaging exam. This paper aims at adding to such navigation
      systems a device that will guide the surgeon towards the target, following a
      complex preplanned ancillary trajectory. We propose to use tactile stimuli for
      such guidance, with the design of a vibrating belt. An experiment using a virtual
      surgery simulator in the case of skull base surgery is conducted with 9 naive
      subjects, assessing the vibrotactile guidance effectiveness for complex
      trajectories. Comparisons between a visual guidance and a visual+tactile guidance
      are encouraging, supporting the relevance of such tactile guidance paradigm.

PMID- 21095950
TI  - Preliminary evaluation of podotactile feedback in sighted and blind users.
AB  - This paper presents preliminary work towards the evaluation of an on-shoe tactile
      display that enables users to obtain information through the sense of touch of
      their feet. A series of experiments were designed to determine the performances
      of 20 healthy sighted and 5 blind voluntary subjects. Tests evaluated the
      perception of simple shapes, patterns, and directional instructions. Results show
      that some information is discriminable and that tactile-foot stimulation could be
      used for a wide number of applications in human-machine interaction. In
      particular, results suggest that the blind perform better in some key tasks and
      that it is feasible to exploit podotactile feedback for mobility and navigation
      assistance of the blind.

PMID- 21095951
TI  - A portable eBook reader for the blind.
AB  - This paper presents the design and first prototype of the TactoBook system, a
      novel concept of reading assistive device that aims to make eBooks accessible to
      the blind. The TactoBook consists of a computer-based software translator that
      converts fast and automatically any eBook into Braille. The Braille version of
      the eBook is then encrypted as a file and stored in a USB memory drive which is
      later inserted and reproduced in a compact, lightweight, and highly-portable
      tactile terminal. Braille readers can store multiple eBooks in the same USB and
      access/reproduce them in the tactile terminal without this being plugged to a
      computer. The first Braille terminal developed is a 10-cell prototype based on a
      piezoelectric ultrasonic actuation approach. Its overall performance is quite
      similar to the one obtained with traditional Braille terminals. However, unlike
      them, the full device is only 1 kg mass and its compact dimensions (20 * 15 * 10
      cm) make it easily carried by the user. A technical overview of all subsystems is
      presented and discussed.

PMID- 21095952
TI  - Inkjet printed arrays of pressure sensors based on all-organic field effect
      transistors.
AB  - In this paper we propose totally flexible organic field effect transistors
      (OFETs) assembled on plastic films as sensors for mechanical variables. First
      mechanical sensors for pressure and bending detection are presented. A sharp and
      reversible sensitivity of the output current of the device to an elastic
      deformation induced by means of a mechanical stimulus on the device channel has
      been observed and suggested the idea of employing arrays of such sensors for
      detecting the deformation applied onto a planar surface. Second the possibility
      of using similar devices for bio- and chemo-detection is described. By exploiting
      the properties of the basic structure, the device can be combined with any kind
      of substrate to detect for instance the pressure applied by people walking or
      standing on a functionalized carpet. This emerging technology seems to be
      promising for applications in the field of remote and non invasive monitoring of
      elderly and disabled people.

PMID- 21095953
TI  - Evaluation and analysis of multimodal sensors for developing in and around the
      bed patient monitoring system.
AB  - Due to the decline in physical and cognitive abilities, many frail elderly may
      have to lie in the bed most of their time. It is not feasible to monitor them
      continuously through manual observations alone. This issue can be resolved by
      embedding a set of multimodal sensors into the bed and providing automated
      activity recognition intelligence. But it is important to design and develop such
      multimodal sensing intelligence system desirable to the demands made by the
      clinicians. This paper presents the comparison and evaluation of different
      sensing bed configurations to observe different granularities of patient's
      contexts and activities in and around the bed. Based on the achievements and
      lessons learned from the experimental analysis, we propose improved sensing bed
      hardware and software systems to meet the real needs of in and around the bed
      patient monitoring.

PMID- 21095954
TI  - Reducing hardware risks in the development of Telematic rescue assistance
      systems: a methodology.
AB  - In developed countries many of the main causes of death such as heart attack and
      stroke usually strike outside of hospitals. Therefore patient outcome depends to
      a large extent on the quality of preclinical care. In order to improve it,
      Telematic Rescue Assistance Systems (TRAS) are being developed. They transmit
      vital signs, audio and sometimes video data from the rescue team to an emergency
      physician at a remote site, thus enabling this specialist to assist in diagnosis
      and treatment. Not only is specialist expertise brought to the emergency site,
      but also time to definite treatment is reduced, as specialists are involved
      earlier and hospitals are informed in advance about incoming patients. Due to
      their use in emergencies, risks to the proper functioning of TRAS hardware have
      to be kept as low as possible. Adequate methods for risk assessment have to be
      chosen, since the use of an inadequate method can result in a cumbersome resource
      intensive process, while at the same time major risks are being overlooked. This
      paper proposes a methodology for reducing hardware risks in the development of
      TRAS.

PMID- 21095955
TI  - Wireless remote monitoring of myocardial ischemia using reconstructed 12-lead
      ECGs.
AB  - CardioBip (CB) is a hand-held patient-activated device for recording and wireless
      transmission of reconstructed 12-lead ECG (12CB) based on patient specific
      matrices. It has 5 contact points: 3 precordial and 2 on the device top serving
      as limb leads when touched by index fingers. To determine whether CB could be
      used to monitor coronary disease (CAD) patients, we compared 12CB to simultaneous
      12-lead ECGs (12L) in patients with CAD, pre-and post-exercise treadmill testing
      (ETT). The study goals were to assess: (1) whether 12CB can accurately
      reconstruct and wirelessly transmit 12-lead ECGs in CAD patients during ETT
      recovery; (2) whether 12CB can be used to evaluate ST segment changes in patients
      with exercise-induced ischemia.

PMID- 21095956
TI  - Real-time low-energy fall detection algorithm with a programmable truncated MAC.
AB  - The ability to discriminate between falls and activities of daily living (ADL)
      has been investigated by using tri-axial accelerometer sensors, mounted on the
      trunk and using simulated falls performed by young healthy subjects under
      supervised conditions and ADL performed by elderly subjects. In this paper we
      propose a power-aware real-time fall detection integrated circuit (IC) that can
      distinguish Falls from ADL by processing the accelerations measured during 240
      falls and 240 ADL. In the proposed fixed point custom DSP architecture, a
      threshold algorithm was implemented to analyze the effectiveness of Programmable
      Truncated Multiplication regarding power reduction while maintaining a high
      output accuracy. The presented system runs a real time implementation of the
      algorithm on a low power architecture that allows up to 23% power savings through
      its digital blocks when compared to a standard implementation, without any
      accuracy loss.

PMID- 21095957
TI  - Novel delta zero crossing regression features for gait pattern classification.
AB  - Many recent research works on gait pattern classification indicates that static
      features are used. This paper describes of extracting novel dynamic features as
      complimentary features for the gait pattern classification. The dynamic features
      are obtained by using regression on the delta zero crossing counts (DeltaZCC) of
      the acceleration signal. The classification results using the filterbank features
      with the novel dynamic features showed an overall accuracy of 97% was achieved.
      This is an improvement of 3% from using the filterbank features alone.

PMID- 21095958
TI  - Automatic seizure detection: going from sEEG to iEEG.
AB  - Several different algorithms have been proposed for automatic detection of
      epileptic seizure based on both scalp and intracranial electroencephalography
      (sEEG and iEEG). Which modality that renders the best result is hard to assess
      though. From 16 patients with focal epilepsy, at least 24 hours of ictal and non
      ictal iEEG were obtained. Characteristics of the seizures are represented by use
      of wavelet transformation (WT) features and classified by a support vector
      machine. When implementing a method used for sEEG on iEEG data, a great
      improvement in performance was obtained when the high frequency containing lower
      levels in the WT were included in the analysis. We were able to obtain a
      sensitivity of 96.4% and a false detection rate (FDR) of 0.20/h. In general, when
      implementing an automatic seizure detection algorithm made for sEEG on iEEG,
      great improvement can be obtained if a frequency band widening of the feature
      extraction is performed. This means that algorithms for sEEG should not be
      discarded for use on iEEG - they should be properly adjusted as exemplified in
      this paper.

PMID- 21095959
TI  - Morphological descriptors for automatic detection of epileptiform events.
AB  - The purpose of this study was to analyze morphological characteristics of
      electroencephalogram (EEG) signals in order to define a representation of
      epileptiform events that can distinguish them from other events occurring in the
      signal. There are several studies on parameterization of EEG signals,
      particularly for automatic detection of paroxysms related to epilepsy.
      Considering that during the automatic detection process the morphological
      characteristics pertaining to these events may get mixed up if only conventional
      descriptors are used, it was necessary to create a new set of parameters that
      reveal more differences between them. The parameters are fed to artificial neural
      networks and the individual and collective contribution of each parameter was
      evaluated by statistical process. The proposed method achieved a success rate of
      80-90%, sensitivity and specificity between 85% and 96%.

PMID- 21095960
TI  - Assisted diagnosis of attention-deficit hyperactivity disorder through EEG
      bandpower clustering with self-organizing maps.
AB  - The electroencephalogram is an attractive clinical tool given its non-invasive
      nature, its ability to reflect real-time changes in local cortical activity, and
      the load of objective bioelectrical measurements that can be derived from it. For
      decades, the electroencephalogram has been successfully used for diagnosing
      epilepsy and schizophrenia, among other brain disorders. This paper focuses in
      the design and implementation of a computer-aided diagnostic tool for
      establishing the likelihood of presence of Attention-Deficit Hyperactivity
      Disorder in children, out of routine electroencephalographic recordings obtained
      during a specific visual stimulation protocol. Classical bandpower features from
      multiple differential recordings are computed and used as features in a
      classifier built from a cooperative ensemble of labeled self-organizing maps.
      Classification accuracy of the proposed system is 0,7 +/- 0,11, as estimated from
      unseen data, a result that points to the idea that such a quantitative diagnostic
      aid could adequately support the diagnostic task of a clinical expert.

PMID- 21095961
TI  - On the use of virtual and augmented reality for upper limb prostheses training
      and simulation.
AB  - Accidents happen and unfortunately people may loose part of their body members.
      Studies have shown that in this case, most individuals suffer physically and
      psychologically. For this reason, actions to restore the patient's freedom and
      mobility are imperative. Traditional solutions require ways to adapt the
      individual to prosthetic devices. This idea is also applied to patients who have
      congenital limitations. However, one of the major difficulties faced by those who
      are fitted with these devices is the great mental effort needed during first
      stages of training. As a result, a meaningful number of patients give up the use
      of theses devices very soon. Thus, this article reports on a solution designed by
      the authors to help patients during the learning phases, without actually having
      to wear the prosthesis. This solution considers Virtual (VR) and Augmented
      Reality (AR) techniques to mimic the prosthesis natural counterparts. Thus, it is
      expected that problems such as weight, heat and pain should not contribute to an
      already hard task.

PMID- 21095962
TI  - Non-thermal irreversible electroporation for deep intracranial disorders.
AB  - Non-thermal irreversible electroporation (N-TIRE) is a new minimally invasive
      technique to kill undesirable tissue. We build on our previous intracranial
      studies in order to evaluate the possibility of using N-TIRE for deep
      intracranial disorders. In this manuscript we describe a minimally invasive
      computed tomography (CT) guided N-TIRE procedure in white matter. In addition, we
      report the electric field threshold needed for white matter ablation (630 - 875
      V/cm) using four sets of twenty 50 us pulses at a voltage-to-distance ratio of
      1000 V/cm. We also confirm the non-thermal aspect of the technique with real time
      temperature data measured at the electrode-tissue interface.

PMID- 21095963
TI  - A study using irreversible electroporation to treat large, irregular tumors in a
      canine patient.
AB  - Irreversible electroporation (IRE) has shown promise for the therapeutic
      treatment of focal disease, including tumors. The effects of treatment are
      dependent on the electric field distribution, which may be predicted with
      numerical modeling. In order to improve the effectiveness and scope of IRE
      therapies, techniques must be developed for designing protocols capable of
      treating large and irregular tumors. We present the findings of a study designing
      an IRE treatment plan for a canine patient using medical imaging analysis and
      reconstruction, numerical modeling, and real-time electrode placement guidance.
      The executed plan was able to alleviate the patient's clinical symptoms without
      damaging any of the nearby sensitive tissues in a complex heterogeneous
      environment.

PMID- 21095964
TI  - Nonlinear dynamic modeling of impaired voice.
AB  - This paper presents a nonlinear dynamic model for the purpose of modeling vowels
      uttered by patients who have problem in the control of voice box muscles. The
      proposed model will be utilized in the detection of speech pathologies and also
      automatic speech recognition systems to enhance patients' communication
      capabilities. The model of this study utilizes feedback, and also a sigmoid
      nonlinear function which is not included in the linear speech production models.
      The nonlinear function allows for the higher order dynamics of the signal to be
      captured and feedback increases dynamicity of the model. The model of the current
      research was applied to discriminate between few voice pathologies and normal
      cases. The statistical analysis of the parameters of the trained model showed
      that these parameters can provide independent and distinct features with which
      pathological classes can be discriminated.

PMID- 21095965
TI  - Comparison of artificial neural networks an support vector machines for feature
      selection in electrogastrography signal processing.
AB  - The paper describes a feature selection process applied to electrogastrogram
      (EGG) processing. The data set is formed by 42 EGG records from functional
      dyspeptic (FD) patients and 22 from healthy controls. A wrapper configuration
      classifier was implemented to discriminate between both classes. The aim of this
      work is to compare artificial neural networks (ANN) and support vector machines
      (SVM) when acting as fitness functions of a genetic algorithm (GA) that performs
      a feature selection process over some features extracted from the EGG signals.
      These features correspond to those that literature shows to be the most used in
      EGG analysis. The results show that the SVM classifier is faster, requires less
      memory and reached the same performance (86% of exactitude) than the ANN
      classifier when acting as the fitness function for the GA.

PMID- 21095966
TI  - A graph based algorithm for postures estimation based on accelerometers data.
AB  - An algorithm is presented in this paper to estimate the activity of a person at
      each time index through a Bayesian approach. It does not require any pre
      processing to identify single activity parts in the signal but can generate some
      instability in the estimated sequences of activities due to its nature. To
      circumvent this issue, the decision is enforced with a graph setting constraints
      between the different activities to be detected. As the method is based on a
      Bayesian approach, training can be used to adapt the algorithm to each person. If
      so, the algorithm shows very good performance.

PMID- 21095967
TI  - Assessment of waist-worn tri-axial accelerometer based fall-detection algorithms
      using continuous unsupervised activities.
AB  - This study aims to evaluate a variety of existing and novel fall detection
      algorithms, for a waist mounted accelerometer based system. Algorithms were
      tested against a comprehensive data-set recorded from 10 young healthy subjects
      performing 240 falls and 120 activities of daily living and 10 elderly healthy
      subjects performing 240 scripted and 52.4 hours of continuous unscripted normal
      activities.

PMID- 21095968
TI  - Analysis of human tremor in patients with Parkinson disease using entropy
      measures of signal complexity.
AB  - Tremor in Parkinson's disease (PD) is a fundamental feature used in the
      determination of disease onset and progression. Traditionally, tremor has been
      evaluated using frequency domain analysis. However, in many cases, this analysis
      did not show significant differences comparing healthy elders and individuals
      with PD. Given its complex nature, recently the interest in nonlinear dynamical
      analysis for better understanding of tremor has grown. In this paper, we examine
      the effect of PD on the complexity of the tremor time series of PD patients using
      the approximate entropy method (ApEn). Tremor was also evaluated in the frequency
      domain. This study involved 11 healthy and 11 PD patients. The peak frequency was
      similar in both groups, while the amplitude and power in the peak frequency and
      the total power were significantly higher in PD patients (p < 0.0001). A
      significant reduction (p < 0.001) in ApEn was observed in PD. ROC analysis showed
      that ApEn differentiated physiological tremor from tremor in PD patients with
      high accuracy. These results are in close agreement with pathophysiological
      fundamentals, and provide evidence that in PD patients the tremor pattern becomes
      less complex. Furthermore, our findings also suggest that ApEn has a high
      clinical potential in assessing PD patients.

PMID- 21095969
TI  - Entropy of the EEG in transition to burst suppression in deep anesthesia:
      Surrogate analysis.
AB  - In this paper 5 methods for the assessment of signal entropy are compared in
      their capability to follow the changes in the EEG signal during transition from
      continuous EEG to burst suppression in deep anesthesia. To study the sensitivity
      of the measures to phase information in the signal, phase randomization as well
      as amplitude adjusted surrogates are also analyzed. We show that the selection of
      algorithm parameters and the use of normalization are important issues in
      interpretation and comparison of the results. We also show that permutation
      entropy is the most sensitive to phase information among the studied measures and
      that the EEG signal during high amplitude delta activity in deep anesthesia is of
      highly nonlinear nature.

PMID- 21095970
TI  - Graph analysis of neuronal interactions for the error-related negativity.
AB  - The brain is a biological system with dynamic interactions between its sub
      systems. The complexity of this system poses a challenge for identifying
      functional networks underlying observed neural activity. Current imaging
      approaches index local neural activity very well, but there is an increasing need
      for methods that quantify the interaction between regional activations. In this
      paper, we focus on inferring the functional connectivity of the brain based on
      electroencephalography (EEG) data. The interactions between the different
      neuronal populations are quantified through a dynamic measure of phase synchrony
      which is used to form sparsely connected networks that can be evaluated using
      measures of graph theory. These measures are applied to an EEG study containing
      the error-related negativity (ERN), a brain potential response that indexes
      endogenous action monitoring, to determine the organization of the brain during a
      decision making task and determine the differences between Error and Correct
      responses from subjects grouped according to an Externalizing Inventory. Results
      conclude weighted clustering coefficient and binary path length measures
      demonstrate significant differences between error low externalizers with all
      other response/externalizer types (error/high, correct/low, and correct/high).

PMID- 21095971
TI  - A novel continuous cardiac output monitor based on pulse wave transit time.
AB  - Monitoring cardiac output (CO) is important for the management of patient
      circulation in an operation room (OR) or intensive care unit (ICU). We assumed
      that the change in pulse wave transit time (PWTT) obtained from an
      electrocardiogram (ECG) and a pulse oximeter wave is correlated with the change
      in stroke volume (SV), from which CO is derived. The present study reports the
      verification of this hypothesis using a hemodynamic analysis theory and animal
      study. PWTT consists of a pre-ejection period (PEP), the pulse transit time
      through an elasticity artery (T(1)), and the pulse transit time through
      peripheral resistance arteries (T(2)). We assumed a consistent negative
      correlation between PWTT and SV under all conditions of varying circulatory
      dynamics. The equation for calculating SV from PWTT was derived based on the
      following procedures. 1. Approximating SV using a linear equation of PWTT. 2. The
      slope and y-intercept of the above equation were determined under consideration
      of vessel compliance (SV was divided by Pulse Pressure (PP)), animal type, and
      the inherent relationship between PP and PWTT. Animal study was performed to
      verify the above-mentioned assumption. The correlation coefficient of PWTT and SV
      became r = -0.710 (p < 0.001), and a good correlation was admitted. It has been
      confirmed that accurate continuous CO and SV measurement is only possible by
      monitoring regular clinical parameters (ECG, SpO2, and NIBP).

PMID- 21095972
TI  - A comparison between local wave speed in the carotid and femoral arteries in
      healthy humans: application of a new method.
AB  - The wave speed (c) and the arrival time of reflected wave (Trw) in the common
      left carotid artery and common left femoral artery have been evaluated in 70
      healthy subjects, aged 35-55 years with a non-invasive method.

PMID- 21095973
TI  - Validity of a new method to estimate mean arterial pressure at brachial level.
AB  - The value of mean arterial pressure (MBP) is of clinical importance, and is
      required for peripheral resistance calculation as well as for central blood
      pressure calibration procedures. MBP is usually estimated at the upper arm using
      systolic and diastolic sphygmomanometers pressure values, as 33% of pulse
      pressure (PP) above diastolic pressure. In a previous work, we proposed to use
      38%. The aim of this study was to investigate the validity of the proposed
      formula to calculate MBP, when assessing subjects with a wide range of blood
      pressure and pulse wave velocity (PWV) levels. In 73 volunteers (56 +/- 10 years,
      range: 27-82; pulse pressure: 59 +/- 12 mmHg, range: 43-86; PWV: 10 +/- 2 m/s,
      range: 8-17) arterial pressure waveforms were obtained at the left brachial
      artery by applanation tonometry. Diastolic (DBP) and systolic (SBP) brachial
      pressure were obtained with oscillometric device. Brachial-radial PWV was
      obtained at the same arm using mechano-transducers. MBP computed as 38% of PP
      above diastolic pressure, introduces an error of only 0.1% in brachial MBP
      estimation, independent of pressure and PWV levels.

PMID- 21095974
TI  - Levels and rates of change in carotid-radial pulse wave velocity associated with
      reactive hyperaemia: Analysis of the dependence on transient ischemia length.
AB  - The analysis of carotid-radial pulse wave velocity (PWVcr) changes in response to
      forearm transient ischemia (TI) has been proposed as an alternative approach to
      evaluate endothelial function. Consider flow mediated dilatation tests, PWVcr
      changes are characterized after 5 minutes of TI. It is unknown if lower TI times
      could be used and if different TI times would result in different PWVcr responses
      (levels and/or kinetics). OBJECTIVE: To determine PWVcr changes associated with
      the reactive hyperemia in response to 1, 3 or 5 minutes of forearm TI. METHODS:
      We measured left PWVcr change using mechano-transducers in healthy volunteers (22
      +/- 2 years old) before (basal) and after 1 (n=14), 3 (n=14) and 5 (n=15) minutes
      of TI (forearm cuff inflation), respectively. The change of level and rate in
      PWVcr were recorded at 15, 30, 45 and 60 seconds after cuff release. Right
      brachial pressure was measured. RESULTS: There were no changes in heart rate or
      blood pressure during the studies. Regardless of the occlusion length, TI
      resulted in PWVcr reduction (p < 0.05). The groups showed similar maximum PWVcr
      reduction. However, there were differences in the immediate PWVcr changes (-4.9
      +/- 0.2%; -6.8 +/- 0.3% and -8.3 +/- 0.5% for 1, 3 and 5 minutes of TI,
      respectively) (p < 0.05). Then, the immediate rate of PWVcr change differed (p <
      0.05) among the different ischemia times considered. Thereafter, the differences
      diminished and a minute after TI the groups showed similar levels and mean rate
      of PWVcr reduction. CONCLUSION: Similar maximum PWVcr responses can be obtained
      after 1, 3, or 5 minutes of TI. Different TI times resulted in dissimilar
      immediate, but not later, PWVcr changes.

PMID- 21095975
TI  - How to quantitatively synthesize dynamic changes in arterial pressure from
      baroreflexly modulated ventricular and arterial properties.
AB  - Baroreflex regulates arterial pressure by modulating ventricular and vascular
      properties. We investigated if the framework of circulatory equilibrium that we
      developed previously (Am J Physiol 2004, 2005) by extending the classic Guyton's
      framework is capable of predicting baroreflex induced changes in arterial
      pressure. In animal experiments, we estimated open loop transfer functions of
      baroreflexly modulated ventricular and vascular properties, synthesized
      baroreflex induced dynamic changes in arterial pressure using the estimated
      transfer functions and compared the predicted responses with measured responses.
      We demonstrated that the predicted baroreflex induced changes in arterial
      pressure matched reasonable well with those measured. We conclude that the
      framework of circulatory equilibrium is generalizable under the condition where
      baroreflex dynamically changes arterial pressure.

PMID- 21095976
TI  - E-Health towards ecumenical framework for personalized medicine via Decision
      Support System.
AB  - The purpose of the present manuscript is to present the advances performed in
      medicine using a Personalized Decision Support System (PDSS). The models used in
      Decision Support Systems (DSS) are examined in combination with Genome
      Information and Biomarkers to produce personalized result for each individual.
      The concept of personalize medicine is described in depth and application of PDSS
      for Cardiovascular Diseases (CVD) and Type-1 Diabetes Mellitus (T1DM) are
      analyzed. Parameters extracted from genes, biomarkers, nutrition habits,
      lifestyle and biological measurements feed DSSs, incorporating Artificial
      Intelligence Modules (AIM), to provide personalized advice, medication and
      treatment.

PMID- 21095977
TI  - Discovery and use of efficient biomarkers for objective disease state assessment
      in Alzheimer's disease.
AB  - Objective and early detection of Alzheimer's disease (AD) is a demanding problem
      requiring consideration of manymodal observations. Potentially, many features
      could be used to discern between people without AD and those at different stages
      of the disease. Such features include results from cognitive and memory tests,
      imaging (MRI, PET) results, cerebral spine fluid data, blood markers etc.
      However, in order to define an efficient and limited set of features that can be
      employed in classifiers requires mining of data from many patient cases. In this
      study we used two databases, ADNI and Kuopio LMCI, to investigate the relative
      importance of features and their combinations. Optimal feature combinations are
      to be used in a Clinical Decision Support System that is to be used in clinical
      AD diagnosis practice.

PMID- 21095978
TI  - An intelligent system for classification of patients suffering from chronic
      diseases.
AB  - The CHRONIOUS system addresses a smart wearable platform, based on multi
      parametric sensor data processing, for monitoring people suffering from chronic
      diseases in long-stay setting. Several signals are being recorded through
      wearable sensors and are stored together with additional information, entered by
      the patient. An Intelligent System, placed at a Smart Assistant Device, analyzes
      incoming data and facilitates data mining techniques resulting upon the severity
      of a health episode. Part of the Intelligent System is the Mental Support Tool,
      which calculates a Stress Index and classifies the mental condition and stress
      levels of the patient. An additional component aiming at the personalization of
      the Intelligent System's Decision is the Profiler which defines several patients
      profiles and facilitates clustering techniques in order to associate each
      patient's description with one of the predefined profiles.

PMID- 21095979
TI  - Decision-making system for orthodontic treatment planning based on direct
      implementation of expertise knowledge.
AB  - Development of the decision-making systems has been highly demanded to provide
      objective evidence for the decisions of experts, especially in medicine, and a
      variety of systems have been developed by means of the state-of-the-art
      technology. In orthodontics, there has been no objective criterion for the
      decisions of whether or not to perform one of the invasive treatments, tooth
      extraction. Therefore, the prediction system for the extraction-nonextraction
      decisions was developed by intuitive implementation of expertise knowledge in
      this study. The system was successfully optimized with respect to knowledge
      descriptions and an inference algorithm to provide the prediction accuracy of
      90.5% and simulations of the decision-making process on the optimized model were
      performed to obtain the terse representation of the expertise knowledge elements
      that are assumed to affect the decision-making of experts.

PMID- 21095980
TI  - Influence of source separation and montage on ictal source localization.
AB  - The aim of this paper is to evaluate the influence of the reference electrode
      (introduced to form an augmented average montage) and of the artifact elimination
      by blind source separation on the ictal electrical source imaging. We present
      here a preliminary study on one patient only. The results seem to indicate that
      the montage (and thus the reference handling method) has a limited but existent
      influence on the quality of the source localization. Artifact elimination highly
      improves this quality as well.

PMID- 21095981
TI  - Neuropolitics: EEG spectral maps related to a political vote based on the first
      impression of the candidate's face.
AB  - The aim of the present research is to investigate the EEG activity elicited by a
      fast observation of face of real politicians during a simulated political
      election. Politician's face are taken from real local election performed in Italy
      in the 2004 and 2008. We recorded the EEG activity of eight healthy subjects
      while they are asked to give a judgment on dominance, trustworthiness traits and
      a preference of vote on faces shown. Statistical differences of spectral EEG
      scalp activity have been mapped onto a realistic head model. For each
      experimental condition, we employed the t-test to compare the PSD values and
      adopted the False Discovery Rate correction for multiple comparisons. The scalp
      statistical maps revealed a desynchronization in the alpha band related to the
      politicians who lost the simulated elections and have been judged less
      trustworthy. Although these results might be congruent with the recent
      literature, the present is the first EEG study about and there is the need to
      extend the paradigm and the analysis on a larger number of subjects to validate
      these results.

PMID- 21095982
TI  - Three-fold cross-validation of parkinsonian brain patterns.
AB  - Abnormal physiological networks of brain areas in disease can be identified by
      applying specialized multivariate computational algorithms based on principal
      component analysis to functional image data. Here we demonstrate the
      reproducibility of network patterns derived using positron emission tomography
      (PET) data in independent populations of parkinsonian patients for a large,
      clinically validated data set comprised of subjects with idiopathic Parkinson's
      disease (iPD), multiple system atrophy (MSA) and progressive supranuclear palsy
      (PSP). Correlation of voxel values of network patterns derived for the same
      condition in different data sets was high. To further illustrate the validity of
      these networks, we performed single subject differential diagnosis of prospective
      test subjects to determine the most probable case based on a subject's network
      scores expressed for each of these distinct parkinsonian syndromes. Three-fold
      cross-validation was performed to determine accuracy and positive predictive
      rates based on networks derived in separate folds of the composite data set. A
      logistic regression based classification algorithm was used to train in each fold
      and test in the remaining two folds. Combined accuracy for each of the three
      folds ranged from 82% to 93% in the training set and was approximately 81% for
      prospective test subjects.

PMID- 21095983
TI  - A Kullback-Leibler methodology for HRF estimation in fMRI data.
AB  - Hemodynamic Response Function (HRF) estimation in functional Magnetic Resonance
      Imaging (fMRI) experiments is an important issue in functional neuroimages
      analysis. Indeed, when modeling each brain region as a stationary linear system
      characterized by its impulse response, the HRF describes the temporal dynamic of
      the brain region response during activations. Using the mixed-effects model, a
      new algorithm for maximum likelihood HRF estimation is derived. In this model,
      the random effect is used to better account for the variability of the drift.
      Contrary to the usual approaches, the proposed algorithm has the benefit of
      considering an unknown drift matrix. Estimations of the HRF and the
      hyperparameters are derived by alternating minimization of the Kullback-Leibler
      divergence between a model family of probability distributions defined using the
      mixed-effects model and a desired family of probability distributions constrained
      to be concentrated on the observed data. The relevance of proposed approach is
      demonstrated both on simulated and real data.

PMID- 21095984
TI  - Estimation of dynamic neural activity using a Kalman filter approach based on
      physiological models.
AB  - This paper presents a new method to estimate dynamic neural activity from EEG
      signals. The method is based on a Kalman filter approach, using physiological
      models that take both spatial and temporal dynamics into account. The filter's
      performance (in terms of estimation error) is analyzed for the cases of linear
      and nonlinear models having either time invariant or time varying parameters. The
      best performance is achieved with a nonlinear model with time-varying parameters.

PMID- 21095985
TI  - Hemodynamic correlates of visuomotor motor adaptation by functional Near Infrared
      Spectroscopy.
AB  - The development of rehabilitation engineering technologies such as the design of
      smart prosthetics necessitates a deep understanding of brain mechanisms engaged
      in ecological situations when human interact with new tools and/or environments.
      Thus, we aimed to investigate potential hemodynamic signatures reflecting the
      level of cognitive-motor performance and/or the internal or mental states of
      individuals when learning a novel tool with unknown properties. These markers
      were derived from functional Near Infrared Spectroscopy (fNIR) signals. Our
      results indicate an increased level of oxy-hemoglobin in prefrontal sensors
      associated with enhanced kinematics during early compared with late learning.
      This is consistent with previous neuroimaging studies that revealed a higher
      contribution of prefrontal areas during early compare to late adaptation
      learning. These non-invasive functional hemodynamic markers may play a role in
      bioengineering applications such as smart neuroprosthesis and brain monitoring
      where adaptive behavior is important.

PMID- 21095986
TI  - Repetitive transcranial magnetic stimulator with controllable pulse parameters
      (cTMS).
AB  - We describe a novel transcranial magnetic stimulation (TMS) device that uses a
      circuit topology incorporating two energy-storage capacitors and two insulated
      gate bipolar transistors (IGBTs) to generate near-rectangular electric field E
      field) pulses with adjustable number, polarity, duration, and amplitude of the
      pulse phases. This controllable-pulse-parameter TMS (cTMS) device can induce E
      field pulses with phase widths of 5-200 us and positive/negative phase amplitude
      ratio of 1-10. Compared to conventional monophasic and biphasic TMS, cTMS reduces
      energy dissipation by 78-82% and 55-57% and decreases coil heating by 15-33% and
      31-41%, respectively. We demonstrate repetitive TMS (rTMS) trains of 3,000 pulses
      at frequencies up to 50 Hz with E-field pulse amplitude and width variability of
      less than 1.7% and 1%, respectively. The reduced power consumption and coil
      heating, and the flexible pulse parameter adjustment offered by cTMS could
      enhance existing TMS paradigms and could enable novel research and clinical
      applications with potentially enhanced potency.

PMID- 21095987
TI  - Towards a Switched-Capacitor based Stimulator for efficient deep-brain
      stimulation.
AB  - We have developed a novel 4-channel prototype stimulation circuit for implantable
      neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS)
      aims to utilize charge storage and charge injection techniques to take advantage
      of both the efficiency of conventional voltage-controlled stimulators (VCS) and
      the safety and controllability of current-controlled stimulators (CCS). The
      discrete SCS prototype offers fine control over stimulation parameters such as
      voltage, current, pulse width, frequency, and active electrode channel via a
      LabVIEW graphical user interface (GUI) when connected to a PC through USB.
      Furthermore, the prototype utilizes a floating current sensor to provide charge
      balanced biphasic stimulation and ensure safety. The stimulator was analyzed
      using an electrode-electrolyte interface (EEI) model as well as with a pair of
      pacing electrodes in saline. The primary motivation of this research is to test
      the feasibility and functionality of a safe, effective, and power-efficient
      switched-capacitor based stimulator for use in Deep Brain Stimulation.

PMID- 21095988
TI  - An architecture for a universal neural stimulator with almost arbitrary current
      waveform.
AB  - This paper describes the architecture and protocol of a digital stimulator which
      is intended to realize a highly flexible stimulation waveform pattern. The
      flexibility is provided by programmable stimulation profiles such as pulse
      duration, frequency, polarity, amplitude level, arbitrary wave shape, train of
      pulses and different types of wave patterns among stimulation sites. The
      programmable stimulation data is therefore divided into two parts, global and
      local stimulation data. The global data which defines the timing of pulse
      duration and wave shaping, are sent sequentially to all stimulation sites using 5
      bit control commands. Local stimulation data defines the initial amplitude
      setting and is stored at each active stimulation cell. At each stimulation site,
      the amplitude level can be changed during the stimulation process and
      consequently it generates an arbitrary wave shape. Without the need of a large
      memory size, the proposed simple design architecture generates not only arbitrary
      stimulation waveforms, but also trains of pulses as well as different types of
      stimulation patterns among stimulation sites are enabled.

PMID- 21095989
TI  - A neurophotonic device for stimulation and recording of neural microcircuits.
AB  - Neural stimulation and recording with high spatiotemporal precision is desirable
      for studying the real time cellular basis of neural circuits, as well as
      developing possible therapeutic treatments for neurological diseases. Optical
      stimulation of genetically targeted neurons expressing the light sensitive ion
      channel protein Channelrhodopsin (ChR2) and Halorhodopsin (NpHR) has recently
      been reported as a means for millisecond temporal control of neuronal spiking
      activity with cell-type selectivity. We combine the new 'optogenetics' approaches
      with a dual-modality device, which consists of a tapered coaxial optical
      waveguide ("optrode") directly integrated into a 36 element intra-cortical multi
      electrode recording array (MEA). This novel optoelectronic microarray was
      cortically implanted in ChR2 transduced behaving rats. We have shown that the
      idiopathic induced epileptic seizure could be modulated by optical stimulation.

PMID- 21095990
TI  - VLSI implementation of a template subtraction algorithm for real-time stimulus
      artifact rejection.
AB  - In this paper, we present very-large-scale integrated (VLSI) implementation of a
      template subtraction algorithm for stimulus artifact rejection (SAR) in real time
      with applicability to closed-loop neuroprostheses. The SAR algorithm is based
      upon an infinite impulse response (IIR) temporal filtering technique, which can
      be efficiently implemented in VLSI with reduced power consumption and silicon
      area. We demonstrate that initialization of the memory within the system
      architecture using the first recorded stimulus artifact significantly decreases
      system response time as compared to the case without memory initialization. Two
      sets of pre-recorded neural data from an Aplysia californica are used to simulate
      the functionality of the proposed VLSI architecture in AMS 0.35 microm
      complementary metal-oxide-semiconductor (CMOS) technology. Depending upon the
      reproducibility in the shape of stimulus artifacts in vivo, the system eliminates
      virtually all artifacts in real time and recovers the extracellular neural
      activity with microW-level power consumption from 1.5 V.

PMID- 21095991
TI  - Using reciprocal derivative chronopotentiometry as a technique to determine safe
      charge injection limits of electrodes used for neural stimulation.
AB  - We used reciprocal derivative chronopotentiometry (RDC) with platinum electrodes
      of 50 microm diameter in 0.15 M phosphate buffered saline solution to identify
      the various electrochemical processes occurring at the electrode during biphasic
      current pulsing. RDC allowed to determine the limits of water hydrolysis based on
      the specific (dt/dE)-E data representation employed in this technique resulting
      in curves similar to the voltammetric i-E response. Current stimulation was
      performed by either varying the pulse amplitude or pulse width. We found that the
      limits for H(2) and O(2) evolution for constant-amplitude pulses lied at 0.51
      mC/cm(2) and 0.67 mC/cm(2), respectively, while for constant-width pulses they
      occurred at slightly lower values of 0.49 mC/cm(2) and 0.61 mC/cm(2),
      respectively. We could also extract values for the anodic and cathodic
      overvoltages associated with gas evolution. The cathodic overvoltage for H(2)
      evolution was 1.43 V for both constant-amplitude and constant-width pulses, while
      the anodic overpotentials for O(2) evolution were 2.45 V in the first and 2.24 V
      in the latter case. These values are clearly larger than the gas evolution limits
      generally found with steady-state voltammetry.

PMID- 21095992
TI  - Pedagogical issues for effective teaching of biosignal processing and analysis.
AB  - Biosignal processing and analysis is generally perceived by many students to be a
      challenging topic to understand, and to become adept with the necessary
      analytical skills. This is a direct consequence of the high mathematical content
      involved, and the many abstract features of the topic. The MATLAB and Mathcad
      software packages offer an excellent algorithm development environment for
      teaching biosignal processing and analysis modules, and can also be used
      effectively in many biosignal, and indeed bioengineering, research areas. In this
      paper, traditional introductory and advanced biosignal processing (and analysis)
      syllabi are reviewed, and the use of MATLAB and Mathcad for teaching and research
      is illustrated with a number of examples.

PMID- 21095993
TI  - Learning by gaming - evaluation of an online game for children.
AB  - Playing computer games is widely popular among children and teenagers as an
      entertainment activity; meanwhile, playing computer games also provides a
      learning opportunity. For example, the rules of the game have to be learned by
      the player in order to improve his/her performance. Based on that principle, the
      City eHealth Research Centre (CeRC) developed a web game for 13-15 year olds,
      whereby the player becomes an investigator who attends the scene of an incident
      that involves microbes. There are four missions in total, each involving a
      mystery that the player needs to solve and learning objectives that need to be
      taught - such as antibiotic resistance and the importance of hygiene. This paper
      presents the results from a game evaluation that took place between July of 2009,
      in four UK schools (Glasgow, Gloucester, London), with 129 students; whereby 98%
      of the students commented positively about playing the game. Subsequently, CeRC
      has improved the game and developed an interactive educational games portal
      (www.edugames4all.com) for different age groups of web game enthusiasts.

PMID- 21095994
TI  - Collaboration for cooperative work experience programs in biomedical engineering
      education.
AB  - Incorporating cooperative education modules as a segment of the undergraduate
      educational program is aimed to assist students in gaining real-life experience
      in the field of their choice. The cooperative work modules facilitate the
      students in exploring different realistic aspects of work processes in the field.
      The track records for cooperative learning modules are very positive. However, it
      is indeed a challenge for the faculty developing Biomedical Engineering (BME)
      curriculum to include cooperative work experience or internship requirements
      coupled with a heavy course load through the entire program. The objective of the
      present work is to develop a scheme for collaborative co-op work experience for
      the undergraduate training in the fast-growing BME programs. A few co
      op/internship models are developed for the students pursuing undergraduate BME
      degree. The salient features of one co-op model are described. The results
      obtained support the proposed scheme. In conclusion, the cooperative work
      experience will be an invaluable segment in biomedical engineering education and
      an appropriate model has to be selected to blend with the overall training
      program.

PMID- 21095995
TI  - Challenges of the biomedical engineering education in Europe.
AB  - Higher education in Europe has passed through a very dynamic period of changes
      during the last ten years. Since the signing of the Bologna Declaration in 1999
      by the Ministers of Education from the EU states, European higher education
      system has aimed toward establishing harmonized programs enabling students and
      teachers to extensively exchange knowledge, ideas and skills. Education in the
      field of Biomedical Engineering has experienced changes also because of the
      research and development in the field which was more intensive than in other
      fields. Besides research in new power sources, it is the most intensive and
      productive research field. Much of the development in BME education in Europe is
      influenced by the European research policy expressed through the 7th Framework
      Programme where health is the major theme. In order to foster and support the
      changes in the European Higher Education Area (EHEA) according to the needs of
      research sector and the labor market, the Tempus scheme of projects was
      established. Tempus scheme aims to support the modernization of higher education
      and create an area of co-operation in the countries surrounding the EU. Our
      Tempus project, CRH-BME "Curricula Reformation and Harmonization in the field of
      Biomedical Engineering" aims to create guidelines for updating existing curricula
      in the field of BME in Europe in order to meet recent and future developments in
      the area, address new emerging interdisciplinary domains that appear as the
      result of the R&D progress and respond to the BME job market demands. In this
      paper, some policy and economic factors affecting BME education in Europe are
      discussed and the results of a BME education survey we prepared within the Tempus
      CHR-BME project are presented. The number of BME programmes in Europe has in the
      last decade significantly increased and there are more BME specializations as the
      result of growing complexity of the research and production in the field.

PMID- 21095996
TI  - Assessment of moral judgment of BME and other health sciences students.
AB  - The accreditation criteria for engineering programs require that the curriculum
      introduce students to the ethical, social, economics and safety issues arising
      from the practice of engineering. This paper presents the assessment of moral
      judgment of biomedical engineering, dentistry and biochemistry students through
      the standardized Defining Issues Test (DIT). Results show that college students,
      as most active members of society, remain at a stage of moral development where
      morality is still predominantly dictated by outside forces. It is expected that
      after formal Ethics studies, students will score higher in the last stages of
      moral development, where laws are regarded as social contracts and moral
      reasoning is based on universal ethical principles.

PMID- 21095997
TI  - Compressive sensing for ultrasound RF echoes using a-Stable Distributions.
AB  - This paper introduces a novel framework for compressive sensing of biomedical
      ultrasonic signals based on modelling data with stable distributions. We propose
      an approach to l(p) norm minimisation that employs the iteratively reweighted
      least squares (IRLS) algorithm but in which the parameter p is judiciously chosen
      by relating it to the characteristic exponent of the underlying alpha-stable
      distributed data. Our results show that the proposed algorithm, which we prefer
      to call S +/- S-IRLS, outperforms previously proposed l(1) minimisation
      algorithms, such as basis pursuit or orthogonal matching pursuit, both visually
      and in terms of PSNR.

PMID- 21095998
TI  - Fusion of multiscale wavelet-based fractal analysis on retina image for stroke
      prediction.
AB  - In this paper, we present a novel method of analyzing retinal vasculature using
      Fourier Fractal Dimension to extract the complexity of the retinal vasculature
      enhanced at different wavelet scales. Logistic regression was used as a fusion
      method to model the classifier for 5-year stroke prediction. The efficacy of this
      technique has been tested using standard pattern recognition performance
      evaluation, Receivers Operating Characteristics (ROC) analysis and medical
      prediction statistics, odds ratio. Stroke prediction model was developed using
      the proposed system.

PMID- 21095999
TI  - Automatic detection of dining plates for image-based dietary evaluation.
AB  - An automatic detector that finds circular dining plates in chronically recorded
      images or videos is reported for the study of food intake and obesity. We first
      detect edges from input images. After a number of processing steps that convert
      edges into curves, arc filtering and grouping algorithms are applied. Then,
      convex hulls are identified and the ones that fit the description of ellipses
      corresponding to dining plates are determined. Our experiments using real-world
      images indicate that this detector is highly reliable and robust even when the
      input images contain complex background scenes and the dining plates are severely
      occluded.

PMID- 21096000
TI  - Model development, testing and experimentation in a CyberWorkstation for Brain
      Machine Interface research.
AB  - The CyberWorkstation (CW) is an advanced cyber-infrastructure for Brain-Machine
      Interface (BMI) research. It allows the development, configuration and execution
      of BMI computational models using high-performance computing resources. The CW's
      concept is implemented using a software structure in which an "experiment engine"
      is used to coordinate all software modules needed to capture, communicate and
      process brain signals and motor-control commands. A generic BMI-model template,
      which specifies a common interface to the CW's experiment engine, and a common
      communication protocol enable easy addition, removal or replacement of models
      without disrupting system operation. This paper reviews the essential components
      of the CW and shows how templates can facilitate the processes of BMI model
      development, testing and incorporation into the CW. It also discusses the ongoing
      work towards making this process infrastructure independent.

PMID- 21096001
TI  - Multimodal fusion of muscle and brain signals for a hybrid-BCI.
AB  - Practical Brain-Computer Interfaces (BCIs) for disabled people should allow them
      to use all their remaining functionalities as control possibilities. Sometimes
      these people have residual activity of their muscles, most likely in the morning
      when they are not exhausted. In this work we fuse electromyographic (EMG) with
      electroencephalographic (EEG) activity in the framework of a so called "Hybrid
      BCI" (hBCI) approach. Thereby, subjects could achieve a good control of their
      hBCI independently of their level of muscular fatigue. Furthermore, although EMG
      alone yields good performance, it is outperformed by the hybrid fusing of EEG and
      EMG. Two different fusion techniques are explored showing graceful performance
      degradation in the case of signal attenuation. Such a system allows a very
      reliable control and a smooth handover if the subjects get exhausted or fatigued
      during the day.

PMID- 21096002
TI  - Reconstructing grasping motions from high-frequency local field potentials in
      primary motor cortex.
AB  - Recent developments in neural interface systems hold the promise to restore
      movement in people with paralysis. In search of neural signals for control of
      neural interface systems, previous studies have investigated primarily single and
      multiunit activity, as well as low frequency local field potentials (LFPs). In
      this paper, we investigate the information content about grasping motion of a
      broad band high frequency LFP (200 Hz - 400 Hz) by classifying discrete grasp
      aperture states and decoding continuous aperture trajectories. LFPs were recorded
      via 96-microelectrode arrays in the primary motor cortex (M1) of two monkeys
      performing free 3-D reaching and grasping towards moving objects. Our results
      indicate that broad band high frequency LFPs could serve as useful signals for
      restoring a motor function such as grasp control.

PMID- 21096003
TI  - Common spatial pattern patches - an optimized filter ensemble for adaptive brain
      computer interfaces.
AB  - Laplacian filters are commonly used in Brain Computer Interfacing (BCI). When
      only data from few channels are available, or when, like at the beginning of an
      experiment, no previous data from the same user is available complex features
      cannot be used. In this case band power features calculated from Laplacian
      filtered channels represents an easy, robust and general feature to control a
      BCI, since its calculation does not involve any class information. For the same
      reason, the performance obtained with Laplacian features is poor in comparison to
      subject-specific optimized spatial filters, such as Common Spatial Patterns (CSP)
      analysis, which, on the other hand, can be used just in a later phase of the
      experiment, since they require a considerable amount of training data in order to
      enroll a stable and good performance. This drawback is particularly evident in
      case of poor performing BCI users, whose data is highly non-stationary and
      contains little class relevant information. Therefore, Laplacian filtering is
      preferred to CSP, e.g., in the initial period of co-adaptive calibration, a novel
      BCI paradigm designed to alleviate the problem of BCI illiteracy. In fact, in the
      co-adaptive calibration design the experiment starts with a subject-independent
      classifier and simple features are needed in order to obtain a fast adaptation of
      the classifier to the newly acquired user's data. Here, the use of an ensemble of
      local CSP patches (CSPP) is proposed, which can be considered as a compromise
      between Laplacians and CSP: CSPP needs less data and channels than CSP, while
      being superior to Laplacian filtering. This property is shown to be particularly
      useful for the co-adaptive calibration design and is demonstrated on off-line
      data from a previous co-adaptive BCI study.

PMID- 21096004
TI  - MRI visualization of a single 15 um navigable imaging agent and future
      microrobot.
AB  - In magnetic resonance imaging (MRI), the susceptibility-based contrast provides a
      way to amplify the effects of a magnetic microparticle, whereas its volume is
      largely inferior to the spatial resolution of the system. This concept presents
      an approach to visualization by means of susceptibility artifact using
      ferromagnetic microparticles. In this work, the amount of the susceptibility
      artifact was investigated using a simulation model and in vitro experiments on
      stainless steel microspheres measuring 40, 20 and 15 microm in diameter. The
      results showed that using a clinical MRI system, a single 15 microm microsphere
      is detectable in gradient-echo scans. The extent of the susceptibility artifact
      was found to be related to the scan parameters and the particles' sizes. Since
      the same ferromagnetic microparticle can be used for MRI-based propulsion, these
      results suggest several potential applications for navigable agents and
      microrobots involved in therapy, diagnostics, and imaging inside the
      microvascular network of the human body.

PMID- 21096005
TI  - A new approach to discriminative HMM training for pathological voice
      classification.
AB  - This paper presents a new approach that improves discriminative training
      criterion for Hidden Markov Models, and is oriented to pathological voice
      identification. This technique is aimed at maximizing the Area under the Curve of
      a receiver operating characteristic curve by adjusting the model parameters using
      as objective function the Mahalanobis distance and the distance between means of
      the underlying probability density functions associated with each class. The
      results show that the proposed technique significantly outperforms the accuracy
      in a classification system compared with other training criteria. Results are
      provided using the MEEIVL voice disorders database.

PMID- 21096006
TI  - Spectral Spatio-Temporal template extraction from EEG signals.
AB  - Analysis of Event Related Potentials (ERPs) produced by brain activities can
      provide insight into the timing of underlying brain function. ERPs can be
      classified by their time/frequency characteristics and spatial location on the
      scalp. Traditionally, ERPs are manually located by temporally and spatially
      averaged EEG signals. This process is error prone and sensitive to a priori
      assumptions. Our proposed algorithm is a general neuroscience-focused data mining
      algorithm that performs time and frequency analysis on ERPs and automatically
      extracts templates corresponding to Spectral Spatio-Temporal (SST) regions
      exhibiting significant differences between experimental outcomes. The method uses
      time-aligned templates, which preserve the characteristics of the signal
      important to cognitive researchers. The ability of the selected signal templates
      to differentiate between stimulus responses has been verified using a pattern
      recognition procedure. SST template extraction is tested on data taken from a
      Go/NoGo task and shown to both find relationships consistent with published
      neuroscience literature as well as novel relationships.

PMID- 21096007
TI  - Creating symbolic representations of electroencephalographic signals: an
      investigation of alternate methodologies on intracranial data.
AB  - The electroencephalogram (EEG) is widely used in the investigation of
      neurological disorders. Continuous long-term EEG data offers the opportunity to
      assess patient health over long periods of time, and to discover previously
      unknown physiological phenomena. However, the sheer volume of information
      generated by long-term EEG monitoring also poses a serious challenge for both
      analysis and visualization. Symbolization has been successful in addressing
      information overload in many disciplines. In this paper, we present different
      approaches to transform EEG signals into symbolic sequences. This discrete
      symbolic representation reduces the amount of EEG data by several orders of
      magnitude and makes the task of discovering and visualizing interesting activity
      more manageable. We describe alternate methodologies to symbolize EEG data from
      patients with epilepsy. When evaluated on long-term intracranial data from 10
      patients, our symbolization produced results that were consistent with clinical
      labels of seizures (for 97% of the seizures and 68% of the seizure segments), and
      often produced finer-grained distinctions.

PMID- 21096008
TI  - An integrated domain specific language for post-processing and visualizing
      electrophysiological signals in Java.
AB  - Electrophysiology of vision - especially the electroretinogram (ERG) - is used as
      a non-invasive way for functional testing of the visual system. The ERG is a
      combined electrical response generated by neural and non-neuronal cells in the
      retina in response to light stimulation. This response can be recorded and used
      for diagnosis of numerous disorders. For both clinical practice and clinical
      trials it is important to process those signals in an accurate and fast way and
      to provide the results as structured, consistent reports. Therefore, we developed
      a freely available and open-source framework in Java (http://www.eye.uni
      tuebingen.de/project/idsI4sigproc). The framework is focused on an easy
      integration with existing applications. By leveraging well-established software
      patterns like pipes-and-filters and fluent interfaces as well as by designing the
      application programming interfaces (API) as an integrated domain specific
      language (DSL) the overall framework provides a smooth learning curve.
      Additionally, it already contains several processing methods and visualization
      features and can be extended easily by implementing the provided interfaces. In
      this way, not only can new processing methods be added but the framework can also
      be adopted for other areas of signal processing. This article describes in detail
      the structure and implementation of the framework and demonstrate its application
      through the software package used in clinical practice and clinical trials at the
      University Eye Hospital Tuebingen one of the largest departments in the field of
      visual electrophysiology in Europe.

PMID- 21096009
TI  - Tunnel morph model for time frequency bio-signal waveform processing.
AB  - In this paper, we proposed a tunnel morph model for bio-signal waveform in
      measuring their similarity. Firstly, the formal specifications of bio-signal
      waveforms are given. And then, a series of model establishing related definitions
      are presented. These definitions contain waveform segmentation; waveforms
      distance measurement, and tunnel width computation. Moreover, on the base of the
      model, a similarity measuring strategy which takes the curve feature of bio
      signal into account was presented. In the end, the strategy was compared with
      other similarity measurement methods by AECG (Ambulatory Electrocardiogram)
      waveform data. The data are adopted from MIT/BIH arrhythmia database. Experiment
      results show that the sensitivity and the positive predictivity of the strategy
      based on tunnel morph model are prior to other strategies.

PMID- 21096010
TI  - Classification of holter registers by dynamic clustering using multi-dimensional
      particle swarm optimization.
AB  - In this paper, we address dynamic clustering in high dimensional data or feature
      spaces as an optimization problem where multi-dimensional particle swarm
      optimization (MD PSO) is used to find out the true number of clusters, while
      fractional global best formation (FGBF) is applied to avoid local optima. Based
      on these techniques we then present a novel and personalized long-term ECG
      classification system, which addresses the problem of labeling the beats within a
      long-term ECG signal, known as Holter register, recorded from an individual
      patient. Due to the massive amount of ECG beats in a Holter register, visual
      inspection is quite difficult and cumbersome, if not impossible. Therefore the
      proposed system helps professionals to quickly and accurately diagnose any latent
      heart disease by examining only the representative beats (the so called master
      key-beats) each of which is representing a cluster of homogeneous (similar)
      beats. We tested the system on a benchmark database where the beats of each
      Holter register have been manually labeled by cardiologists. The selection of the
      right master key-beats is the key factor for achieving a highly accurate
      classification and the proposed systematic approach produced results that were
      consistent with the manual labels with 99.5% average accuracy, which basically
      shows the efficiency of the system.

PMID- 21096011
TI  - Syllable-based speech recognition using EMG.
AB  - This paper presents a silent-speech interface based on electromyographic (EMG)
      signals recorded in the facial muscles. The distinctive feature of this system is
      that it is based on the recognition of syllables instead of phonemes or words,
      which is a compromise between both approaches with advantages as (a) clear
      delimitation and identification inside a word, and (b) reduced set of
      classification groups. This system transforms the EMG signals into robust-in-time
      feature vectors and uses them to train a boosting classifier. Experimental
      results demonstrated the effectiveness of our approach in three subjects,
      providing a mean classification rate of almost 70% (among 30 syllables).

PMID- 21096012
TI  - Shape analysis and clustering of Surface EMG Data.
AB  - Functional Data Analysis (FDA) is a recent field in data analysis and processing.
      It provides efficient methods and tools by considering the analyzed data as
      realizations of functions. In this discipline, raised shape analysis approaches.
      Among them, the Core Shape Modelling (CSM) furnished statistical tools for the
      evaluation of the shape dispersion among a set of curves. In this work, it is
      proposed to use this approach to study Surface EMG (SEMG) Data. These data
      represent electrical activity elicited during muscle contractions and measured on
      the surface of the skin. The generation of the SEMG signal is dependent on many
      morphological, physiological and neural parameters. In fact, the neural
      parameters tune the spatial and time recruitment of the Motor Units (MUs). In
      this study, the CSM algorithm is applied to detect MUs firing synchrony on SEMG
      data simulated using a realistic generation model. The generation parameters
      induce several variabilities and compensatory effects on SEMG data that could
      complicate and bias the data processing task. After phase realignment, a shape
      clustering is done on SEMG amplitude histograms using CSM formalism for different
      MU synchrony classes. The obtained results are promising and demonstrate the
      ability of shape analysis using the CSM approach to detect and classify MUs
      firing synchrony levels in SEMG data despite the present variabilities.

PMID- 21096014
TI  - A multiclass multivariate group comparison test: Application to drug safety.
AB  - Hypothesis tests are used to compare and show the efficiency of drugs. However,
      usual tests do not perform properly whenever the number of variables is greater
      than, or of the same order of magnitude as, the number of observations. In this
      paper, we propose an alternative to usual multiclass multivariate group
      comparison tests such as MANOVA or Wilcoxon tests. We present a pattern
      recognition approach to compare drugs in high dimensional spaces. Our test is
      based on the classification probability of error of a classifier. The decision
      statistics is obtained using the leave one out procedure. The statistics power
      density function has been experimentally shown independent from the data
      distribution under the null hypothesis, that allows to determine the threshold,
      or the p-values, of our test. This test has been applied on clinical data
      registered to ensure the safety side and tolerability of drugs tested.

PMID- 21096013
TI  - Complex-valued spatial filters for task discrimination.
AB  - The method of common spatial patterns (CSP) has been widely adopted for the
      discrimination of mental tasks using EEG data. In this paper, some limitations of
      the standard CSP implementation when considering data where phase relationships
      play a significant role are highlighted. Furthermore, a variant of the CSP method
      based on the analytic representation of signals is proposed to make up for these
      drawbacks. The advantages of the proposed method over the standard CSP
      implementation are demonstrated using simulated data and tests with real EEG
      data. Specifically, it is shown that the complex-valued spatial filters and the
      derived spatial patterns can improve the discrimination process and give a more
      adequate representation of the tasks being considered, respectively.

PMID- 21096015
TI  - An alpha-stable model for ultrasound speckle statistics in skin.
AB  - Characterization of biological tissues in ultrasound images is often tackled
      using empirical pre-Rayleigh distributions. However, the absence of a theoretical
      explanation to these distributions hinders their improvement and clinical
      interpretation. This paper presents a novel model that extends classic
      statistical theories to speckle in biological tissues and explains the existing
      pre-Rayleigh distributions. Furthermore, statistics derived from the proposed
      model outperform the state of the art in skin tissue characterization. Finally,
      promising results in characterization of skin melanoma tumors set the basis for
      the development of reliable ultrasound-based diagnosis techniques.

PMID- 21096016
TI  - Role of fuzzy pre-classifier for high performance LI/MA segmentation in B-mode
      longitudinal carotid ultrasound images.
AB  - The automated segmentation of the carotid artery wall from ultrasound images is
      required for an accurate measurement of the artery intima-media thickness.
      Segmentation accuracy of automated techniques is usually limited by noise and
      artifacts. In 2005, the authors developed a methodology called CULEX whose
      performance was noise sensitive. The final stage of CULEX segmentation was fuzzy
      clustering of the pixels, to detect the lumen-intima (LI) and media-adventitia
      (MA) carotid wall interfaces. In this paper, we show the effect of a fuzzy
      Mamdani-type pre-classifier used to improve the segmentation performance. Thanks
      to the Mamdami fuzzy pre-classifier, we optimized the de-fuzzyfication threshold,
      increasing the LI and MA performance by 62% and 3.5%, respectively. The obtained
      segmentation errors (55.6 +/- 69.4 microm for LI and 34.4 +/- 24.4 microm for
      MA), validated against human tracings and on a 200-images dataset containing a
      mixture of healthy and plaque vessels.

PMID- 21096017
TI  - Ultrasound Biomicroscopy for In vivo architectural characterization of
      gastrocnemius muscle from rats.
AB  - This work applies the Ultrasound Biomicroscopy (UBM) technique to quantify the
      pennation angle (PA) and muscle thickness (MT) of rats' gastrocnemius muscle and
      to determine the reliability of these measurements. UBM (40MHz) images of five
      Wistar female rats were acquired at two ankle positions (neutral and full
      extension) and in two different days. A total of 320 images were processed to
      quantify PA and MT and a statistical analysis assessed data variability and
      reliability. The coefficients of variation were 9.37 and 3.97% for PA and MT,
      respectively, for the ankle at full extension and 15.41 and 4.99% for the ankle
      at neutral position. Pearson correlation between two repeated measurements in the
      same image were 0.93 and 0.99 for PA and MT, respectively. The results indicate
      that UBM is suitable for quantitative muscle architectural characterization and
      can be used in future muscle biomechanical studies.

PMID- 21096018
TI  - Automatic localization and segmentation of colelithiasis crystals in ultrasound
      images.
AB  - This paper presents a new method of localization and segmentation of
      colelithiasis crystals. This disease is characterized by crystals which are
      composed by irregular substances in the bile that appear in the gallbladder and
      can cause pain to the individual. Since the actual evaluation is done by
      radiologists and lacks precise, objective and quantitative assert, we present an
      algorithm which locates and segments the crystals using RunningHills algorithm,
      giving a quantitative approach to the diagnostic of this disease.

PMID- 21096019
TI  - A spectral k-means approach to bright-field cell image segmentation.
AB  - Automatic segmentation of bright-field cell images is important to cell
      biologists, but difficult to complete due to the complex nature of the cells in
      bright-field images (poor contrast, broken halo, missing boundaries). Standard
      approaches such as level set segmentation and active contours work well for
      fluorescent images where cells appear as round shape, but become less effective
      when optical artifacts such as halo exist in bright-field images. In this paper,
      we present a robust segmentation method which combines the spectral and k-means
      clustering techniques to locate cells in bright-field images. This approach
      models an image as a matrix graph and segment different regions of the image by
      computing the appropriate eigenvectors of the matrix graph and using the k-means
      algorithm. We illustrate the effectiveness of the method by segmentation results
      of C2C12 (muscle) cells in bright-field images.

PMID- 21096020
TI  - Soft thresholding for medical image segmentation.
AB  - A new soft thresholding method is presented. The method is based on relating each
      pixel in the image to the different regions via a membership function, rather
      than through hard decisions. The membership function of each of the regions is
      derived from the histogram of the image. As a consequence, each pixel will belong
      to different regions with a different level of membership. This feature is
      exploited through spatial processing to make the thresholding robust to noisy
      environments.

PMID- 21096021
TI  - Stery-hand: A new device to support hand disinfection.
AB  - Incomplete disinfection can cause serious complications in surgical care. The
      teaching of effective hand washing is crucial in modern medical training. To
      support the objective evaluation of hand disinfection, we developed a compact,
      mobile device, relying on digital imaging and image processing. The hardware
      consists of a metal case with matte black interior, ultra-violet lighting and a
      digital camera. Image segmentation and clustering are performed on a regular
      notebook. The hand washing procedures performed with a soap mixed with UV
      reflective powder. This results the skin showing bright under UV light only on
      the treated (sterile) surfaces. When the surgeon inserts its hands into the box,
      the camera placed on the top takes an image of the hand for evaluation. The
      software performs the segmentation and clustering automatically. First, the hand
      contour is determined from the green intensity channel of the recorded RGB image.
      Then, the pixels of the green channel belonging to the hand are partitioned to
      three clusters using a quick, histogram based fuzzy c-means algorithm. The
      optimal threshold between the intensities of clean and dirty areas is extracted
      using these clusters, while the final approximated percentage of the clean area
      is computed using a weighting formula. The main advantage of our device is the
      ability to obtain objective and comparable result on the quality of hand
      disinfection. It may find its best use in the clinical education and training.

PMID- 21096022
TI  - Towards unobtrusive in vivo monitoring of patients prone to falling.
AB  - Falling is a serious health problem for many elderly. To investigate whether the
      higher fall incidence in elderly is due to a higher probability of experiencing
      near falls in daily life, it is necessary to evaluate the stumble incidence of
      elderly in daily life. Accelerometers are already frequently used for in vivo
      activity monitoring. The current study investigates whether an ambulant and
      unobtrusive accelerometer can identify stumbles from treadmill walking using a
      wavelet based detection approach. Seventy nine healthy subjects walked on a
      treadmill with a triaxial accelerometer attached at the level of the sacrum.
      Stumbles were induced using a specially designed braking system (The TRiP). The
      TRiP evoked 30 stumbles at different phases of the swing phase. A wavelet-based
      detection algorithm is used to isolate the stumbles from treadmill walking, with
      a specificity of 99.9% and a sensitivity of 98.4%.

PMID- 21096023
TI  - A novel object-oriented stereo matching on multi-scale superpixels for low
      resolution depth mapping.
AB  - This paper presents a novel object-oriented stereo matching on multi-scale
      superpixels to generate a low-resolution depth map. It overcomes the classic
      downsampling methods' disadvantages, such as boundary blurring, outlier
      enlargement and foreground objects merging to background, etc. The approach we
      exploited is to segment the image in three scales' superpixels from dense to
      sparse ones according to downsampling scale first, then compute disparity
      directly on superpixel's stereo matching. The post-processing of region
      constraint and local refinement uses hierarchical multi-scale superpixels as
      well. The proposed approach is validated on Middle-bury test-bed, and the
      experimental results outperform the current state-of-the-art stereo matching
      methods in low resolutions.

PMID- 21096024
TI  - Analysis of lipid vesicle populations from microscopy video sequences.
AB  - Conducting research on lipid vesicles is very convenient, since they provide a
      stable and controllable environment for in vitro observations. Their resemblance
      to biological cell membranes allows biologists to assess hazardous potential of
      nanoparticles by exposing the vesicles instead of live organisms. When
      considering behavior of vesicles during incubation with nanoparticles, majority
      of existing research focus on observing single vesicles only. Our approach
      provides an ability to observe thousands of lipid vesicles for more
      representative behavior estimation. We developed an efficient algorithm to
      transform video sequences acquired with video microscopy into quantitative data.
      This includes steps required to filter noise, use multiple frames for more
      precise content presentation, detection of regions of interest, and segmentation
      of circular and non-primitively shaped vesicles. Presented work is a crucial step
      towards the creation of an automated computer analysis for lipid vesicles
      behavior assessment.

PMID- 21096025
TI  - Improving a CAD system using bilateral information.
AB  - Computer Aided Detection (CAD) mammographic systems are used in medicine to
      assist radiologists in the evaluation of mammographic images. The aim of this
      work is to compare the results of a developed single-image CAD system with a new
      one, dual-image CAD, that adds registration information of bilateral mammographic
      images in the training step of the former system. The evaluation of the different
      registration methods is performed using similarity measures. Receiver Operating
      Characteristic (ROC) analysis and Free Receiver Operating Characteristics (FROC)
      analysis are used to compare the results of both CAD systems. At a sensitivity of
      80%, the false positives per image was 1.68 for the single-image CAD system and
      0.90 for the dual-image CAD system. The results shows the benefits of integrating
      bilateral information into the CAD system.

PMID- 21096026
TI  - Selection of sampling rate for EMG pattern recognition based prosthesis control.
AB  - Most previous studies of electromyography (EMG) pattern recognition control of
      multifunctional myoelectric prostheses adopted a conventional sampling rate that
      is commonly used in EMG research fields. However, it is unknown whether using a
      lower sampling rate in EMG acquisition still preserves sufficient neural control
      information for accurate classification of user movement intents. This study
      investigated the effects of EMG sampling rate on the performance of EMG pattern
      recognition in identifying 11 classes of arm and hand movements. Our results
      showed that decreasing the sampling rate from 1 kHz to 500 Hz only caused 0.8%
      reduction of the average classification accuracy over five able-bodied subjects
      and 2.2% decrease over two transradial amputees. When using a 400 Hz sampling
      rate, the average classification accuracy decreased 1.3% and 2.8% in able-bodied
      subjects and amputees, respectively. These results suggest that a sampling rate
      between 400-500 Hz would be optimal for EMG acquisition in EMG pattern
      recognition based control of a multifunctional prosthesis.

PMID- 21096027
TI  - A multigrasp hand prosthesis for transradial amputees.
AB  - This paper presents the design of a multi-degree-of-freedom, anthropomorphic hand
      for transradial amputees, and also presents experimental data characterizing its
      performance. Unlike state-of-the-art commercially available prosthetic hands, the
      hand described herein is capable of providing eight canonical postures (and
      movement between these postures). The experimental characterization includes its
      capability to provide eight canonical grasp postures; the frequency response of
      finger motion; and its grasping force capability (as a function of finger
      position). Other performance specifications, such as total mass and audible
      noise, are also provided.

PMID- 21096028
TI  - Structural preservation of deafferented cortex induced by electrical stimulation
      of a sensory peripheral nerve.
AB  - Any manipulation to natural sensory input has direct effects on the morphology
      and physiology of the Central Nervous System. In the particular case of
      amputations, sensory areas of the brain undergo degenerative processes with a
      marked reduction in neuronal activity and global disinhibition. This is probably
      due to a deregulation of the circuits devoted to the control of the cortical
      activity. These changes are detected in the organization of the representational
      maps, the metabolic labeling by 2-deoxyglucose or cytochrome oxidase, the density
      of afferent and efferent axonal connections and the reduced expression of
      inhibitory neurotransmitters. In the present study, performed in animals, we have
      evaluated the therapeutic potential of Brain Machine Interfaces in reversing or
      limiting the degenerative/deregulation processes of amputations. Applying
      electrical stimulation on amputated peripheral nerves, we have achieved to
      maintain in approximately normal values 1) the cortical activity and 2) the
      expression of GABA-associated molecules of the inhibitory interneurons of the
      primary somatosensory cortex.

PMID- 21096029
TI  - Acquisition of myoelectric signals to control a hand prosthesis with implantable
      epimysial electrodes.
AB  - The acquisition of myoelectric signals from the Musculus deltoideus of a rhesus
      monkey is described. Such signals are aimed to be used as control signal for an
      active myoelectric hand prosthesis. For recording, implantable flexible,
      polyimide-based multi-site microelectrodes were placed epimysially on the muscle.
      EMG signals were recorded during voluntary goal-directed movements of the arm,
      and analyzed with respect to signal amplitude and frequency.

PMID- 21096030
TI  - Toward improved sensorimotor integration and learning using upper-limb prosthetic
      devices.
AB  - To harness the increased dexterity and sensing capabilities in advanced
      prosthetic device designs, amputees will require interfaces supported by novel
      forms of sensory feedback and novel control paradigms. We are using a motorized
      elbow brace to feed back grasp forces to the user in the form of extension
      torques about the elbow. This force display complements myoelectric control of
      grip closure in which EMG signals are drawn from the biceps muscle. We expect
      that the action/reaction coupling experienced by the biceps muscle will produce
      an intuitive paradigm for object manipulation, and we hope to uncover neural
      correlates to support this hypothesis. In this paper we present results from an
      experiment in which 7 able-bodied persons attempted to distinguish three objects
      by stiffness while grasping them under myoelectric control and feeling reaction
      forces displayed to their elbow. In four conditions (with and without force
      display, and using biceps myoelectric signals ipsilateral and contralateral to
      the force display,) ability to correctly identify objects was significantly
      increased with sensory feedback.

PMID- 21096031
TI  - Automatic annotation of actigraphy data for sleep disorders diagnosis purposes.
AB  - The diagnosis of Sleep disorders, highly prevalent in the western countries,
      typically involves sophisticated procedures and equipments that are intrusive to
      the patient. Wrist actigraphy, on the contrary, is a non-invasive and low cost
      solution to gather data which can provide valuable information in the diagnosis
      of these disorders. The acquired data may be used to infer the Sleep/Wakefulness
      (SW) state of the patient during the circadian cycle and detect abnormal
      behavioral patterns associated with these disorders. In this paper a classifier
      based on Autoregressive (AR) model coefficients, among other features, is
      proposed to estimate the SW state. The real data, acquired from 23 healthy
      subjects during fourteen days each, was segmented by expert medical personal with
      the help of complementary information such as light intensity and Sleep e-Diary
      information. Monte Carlo tests with a Leave-One-Out Cross Validation (LOOCV)
      strategy were used to assess the performance of the classifier which achieves an
      accuracy of 96%.

PMID- 21096032
TI  - Automatic detection of a phases of the cyclic alternating pattern during sleep.
AB  - This study aimed to develop an automatic algorithm to detect the activation
      phases (A phases) of the Cyclic Alternating Pattern. The sleep EEG microstructure
      of 4 adult, healthy subjects was scored by a sleep medicine expert. Features were
      calculated from each of the six EEG bands (low delta, high delta, theta, alpha,
      sigma and beta), and three additional characteristics were computed: the Hjorth
      activity in the low delta and high delta bands, and the differential variance of
      the raw EEG signal. The correlation between couples of features was analyzed to
      find redundancies for the automatic analysis. The features were used to train an
      Artificial Neural Network to automatically find the A phases of CAP. The data
      were divided into training, validation and testing set, and the visual scoring
      provided by the clinician was used as the desired output. The statistics on the
      second by second classification show an average sensitivity equal to 76%,
      specificity equal to 83% and accuracy equal to 82%. The results obtained are
      encouraging, since an automatic classification of the A phases could benefit the
      practice in clinics, preventing the physician from the time-consuming activity of
      visually scoring the sleep microstructure over the whole eight-hour sleep
      recordings. Moreover, it would provide an objective criterion capable of
      overcoming the problems of inter-scorer variability.

PMID- 21096033
TI  - Sleep/wake detection based on cardiorespiratory signals and actigraphy.
AB  - We investigated the potential of adding cardiac and respiratory activity
      information to actigraphy for sleep-wake staging. A dataset of 35 recordings with
      full polysomnography and actigraphy was used to assess the performance of an
      automated sleep/wake Bayesian classifier using electrocardiogram, inductance
      plethysmogram estimate of respiratory effort and actigraphy. The best performance
      was achieved with the linear discriminant model that provided an agreement of
      Cohen's kappa=0.62 for one of the configurations of the classifier, corresponding
      to an accuracy of 86.8%, a sensitivity of 66.9% and a specificity of 93.1%. It
      shows that combining different vital signs for a home sleep-wake staging system
      could be a promising approach.

PMID- 21096034
TI  - REM behaviour disorder detection associated with neurodegenerative diseases.
AB  - Abnormal skeleton muscle activity during REM sleep is characterized as REM
      Behaviour Disorder (RBD), and may be an early marker for different
      neurodegenerative diseases. Early detection of RBD is therefore highly important,
      and in this ongoing study a semi-automatic method for RBD detection is proposed
      by analyzing the motor activity during sleep. METHOD: A total number of twelve
      patients have been involved in this study, six normal controls and six patients
      diagnosed with Parkinsons Disease (PD) with RBD. All subjects underwent at least
      one ambulant polysomnographic (PSG) recording. The sleep recordings were scored,
      according to the new sleep-scoring standard from the American Academy of Sleep
      Medicine, by two independent sleep specialists. A follow-up analysis of the
      scoring consensus between the two specialists has been conducted. Based on the
      agreement of the two manual scorings, a computerized algorithm has been attempted
      implemented. By analysing the REM and non-REM EMG activity, using advanced signal
      processing tools combined with a statistical classifier, it is possible to
      discriminate normal and abnormal EMG activity. Due to the small number of
      patients, the overall performance of the algorithm was calculated using the leave
      one-out approach and benchmarked against a previously published
      computerized/visual method. RESULTS: Based on the available data and using
      optimal settings, it was possible to correctly classify PD subjects with RBD with
      100% sensitivity, 100% specificity, which is an improvement compared to previous
      published studies. CONCLUSION: The overall result indicates the usefulness of a
      computerized scoring algorithm and may be a feasible way of reducing scoring
      time. Further enhancement on additional data, i.e. subjects with idiopathic RBD
      (iRBD) and PD without RBD, is needed to validate its robustness and the overall
      result.

PMID- 21096035
TI  - Automated polysomnogram artifact compensation using the generalized singular
      value decomposition algorithm.
AB  - Manual/visual polysomnogram (psg) analysis is a standard and commonly implemented
      procedure utilized in the diagnosis and treatment of sleep related human
      pathologies. Current technological trends in psg analysis focus upon translating
      manual psg analysis into automated/computerized approaches. A necessary first
      step in establishing efficient automated human sleep analysis systems is the
      development of reliable pre-processing tools to discriminate between
      outlier/artifact instances and data of interest. This paper investigates the
      application of an automated approach, using the generalized singular value
      decomposition algorithm, to compensate for specific psg artifacts.

PMID- 21096036
TI  - Energy expenditure estimation using triaxial accelerometry and barometric
      pressure measurement.
AB  - Energy expenditure (EE) is a parameter of great relevance in studies involving
      the assessment of physical activity. However, most reliable techniques for EE
      estimation are impractical for use in free-living environments, and those which
      are practically useful often poorly track EE when the subject is working to
      change their altitude, for example when ascending or descending stairs or slopes.
      The aim of this study is to evaluate the utility of adding barometric pressure
      related features, as a surrogate measure for altitude, to existing accelerometry
      related features to estimate the subject's EE. The EE estimation system described
      is based on a triaxial accelerometer (triax) and a barometric pressure sensor.
      The device is wireless, with Bluetooth connectivity for data retrieval, and is
      mounted at the subject's waist. Using a number of features extracted from the
      triax and barometric pressure signals, a linear model is trained for EE
      estimation. This EE estimation model is compared to its counterpart, which solely
      utilizes accelerometry signals. A protocol (comprising lying, sitting, standing,
      walking phases) was performed by 13 healthy volunteers (8 male and 5 female; age:
      23.8 +/- 3.7 years; weight: 70.5 +/- 14.9 kg), whose instantaneous oxygen uptake
      was measured by means of an indirect calorimetry system. The model incorporating
      barometric pressure information estimated the oxygen uptake with the lowest mean
      square error of 4.5 +/- 1.7 (mlO(2).min(-1).kg(-1))(2), in comparison to 7.1 +/-
      2.3 (mlO(2).min(-1).kg(-1))(2) using only accelerometry-based features.

PMID- 21096037
TI  - A Sensor Middleware for integration of heterogeneous medical devices.
AB  - In this paper, the architecture of a modular, service-oriented, Sensor Middleware
      for data acquisition and processing is presented. The described solution was
      developed with the purpose of solving two increasingly relevant problems in the
      context of modern pHealth systems: i) to aggregate a number of heterogeneous, off
      the-shelf, devices from which clinical measurements can be acquired and ii) to
      provide access and integration with an 802.15.4 network of wearable sensors. The
      modular nature of the Middleware provides the means to easily integrate pre
      processing algorithms into processing pipelines, as well as new drivers for
      adding support for new sensor devices or communication technologies. Tests
      performed with both real and artificially generated data streams show that the
      presented solution is suitable for use both in a Windows PC or a Windows Mobile
      PDA with minimal overhead.

PMID- 21096038
TI  - Estimated venous return surface and cardiac output curve precisely predicts new
      hemodynamics after volume change.
AB  - In our extended Guyton's model, the ability of heart to pump blood is
      characterized by a cardiac output curve and the ability of vasculature to pool
      blood by a venous return surface. These intersect in a three-dimensional
      coordinate system at the operating right atrial pressure, left atrial pressure,
      and cardiac output. The baseline cardiac output curve and venous return surface
      and their changes after volume change would predict new hemodynamics. The
      invasive methods needed to precisely characterize cardiac output curve and venous
      return surface led us to aim at estimating cardiac output curve and venous return
      surface from a single hemodynamic measurement. Using the average values for two
      logarithmic function parameters, and for two slopes of a surface, we were able to
      estimate cardiac output curve and venous return surface. The estimated curve and
      surface predicted new hemodynamics after volume change precisely.

PMID- 21096039
TI  - Heuristics to determine ventilation times of ICU patients from the MIMIC-II
      database.
AB  - Mechanical ventilation is an important life support tool for patients in
      intensive care units (ICU). For various research purposes related to patient
      hemodynamic and cardiopulmonary monitoring, it is important to know when a
      patient is on a ventilator. Unfortunately, the widely used MIMIC-II database
      contains results from user charted data, where the user did not always store
      ventilation on and off times explicitly and accurately. The resulting ventilation
      related data are subject to error. Therefore, there are no simple rules to define
      ventilation times retrospectively for this dataset. Hence, we designed a simple
      set of rules to determine the ventilation times using multiple sources of
      mechanical ventilator-related settings and physiological measurements by expert
      heuristics. The rules worked well in comparison with nursing notes regarding
      ventilation events. We conclude that our rule sets for determining ventilation
      times may be useful in assisting with MIMIC-II database analysis.

PMID- 21096040
TI  - Evaluation of monitoring cardiac output by long time interval analysis of a
      radial arterial blood pressure waveform using the MIMIC II database.
AB  - We recently proposed a technique to estimate relative cardiac output (CO) change
      by unique long time interval analysis (LTIA) of a radial arterial blood pressure
      waveform. Here, we evaluated the technique in 169 critically ill patients, while
      comparing it to previous "pulse contour analysis" techniques, using the public
      MIMIC II database. The LTIA technique achieved an overall calibrated CO error of
      18.8% against reference (single determination) thermodilution measurements. This
      level of accuracy was not better than the previous techniques. However, the
      average absolute thermodilution CO change in each patient was only 12.3%. As the
      absolute CO change increased, the LTIA technique became increasingly more
      accurate than the previous techniques.

PMID- 21096041
TI  - Preliminary study of physiological control for the undulation pump ventricular
      assist device.
AB  - The undulation pump ventricular assist device (UPVAD) is a small implantable
      ventricular assist device using an undulation pump. The UPVAD can produce
      pulsatile flow by changing the motor rotation speed of the UPVAD. Because the
      undulation pump is a volume displacement type pump, the inflow sucking occurs
      easily. The purpose of this study is to develop a suitable control method for the
      UPVAD. The UPVAD inflow cannula equipped with an implantable pressure sensor was
      inserted into the ventricle. Therefore, pressure variation that synchronized with
      the natural heartbeat and negative pressure spike caused the inflow sucking were
      observed. By changing the motor rotation speed that responded to the inflow
      pressure, the UPVAD could synchronize with the natural heartbeat and the UPVAD
      could generate a co-pulse assist flow. The inflow sucking could be released by
      reducing the motor rotation speed, if the inflow sucking was detected. The newly
      developed control method exhibited superior characteristics than existing ones
      due to high immunity against pressure sensor drift. The assist flow could be
      increased more than 15% and the inflow sucking occurrence could be decreased with
      this control method. The UPVAD could generate the suitable assist flow with the
      developed control method.

PMID- 21096042
TI  - Automated drug delivery system for the management of hemodynamics and cardiac
      energetic in acute heart failure.
AB  - We have developed a novel automated drug delivery system for simultaneous control
      of systemic arterial pressure (AP), cardiac output (CO), and left atrial pressure
      (P(LA)) in acute heart failure. The circulatory equilibrium framework we
      established previously discloses that AP, CO, and P(LA) are determined by
      equilibrium of the mechanical properties of the circulation, i.e. pumping ability
      of the left heart, stressed blood volume and systemic arterial resistance. Our
      system directly controls the three mechanical properties with cardiovascular
      drugs including inotropes and vasodilators, thereby controlling AP, CO, and
      P(LA). Furthermore, by precisely controlling bradycardia and LV inotropy, our
      system enables to improve cardiac energetic efficiency while preserving AP, CO,
      and P(LA) within acceptable ranges. In conclusion, by directly controlling the
      mechanical properties of the heart and vessel, our automated system realizes
      comprehensive management of hemodynamics in acute heart failure.

PMID- 21096043
TI  - Different models for predicting driving performance in people with brain
      disorders.
AB  - Data from performance on a computerized battery of driving-related sensory-motor
      and cognitive tests (SMCTestsTM) were used to predict outcome on a blinded on
      road driving assessment in 501 people with brain disorders. Six modelling
      approaches were assessed: discriminant analysis (DA), binary logistic regression
      (BLR), nonlinear causal resource analysis (NCRA), and three kernel methods
      (product kernel density (PK), kernel-product density (KP), and support vector
      machine (SVM)). At the classification level, the three kernel methods were more
      accurate for predicting on-road Pass or Fail (SVM 99%, PK 99%, KP 80%) than the
      other models (DA 75%, BLR 77%, NCRA 66%). However, accuracy decreased
      substantially across the kernel models when leave-one-out cross-validation was
      used to estimate how accurately the models would predict on-road Pass or Fail in
      an independent referral group (SVM 76%, PK 73%, KP 72%) but remained fairly
      constant for DA (74%) and BLR (76%). Cross-validation of NCRA was not possible.
      While kernel-based models are successful at modelling complex data at a
      classification level, this appears to be due to overfitting of the data which
      does not improve accuracy in an independent data set over and above the accuracy
      of other modelling techniques.

PMID- 21096044
TI  - Model-based inference of cognitive processes from unobtrusive gait velocity
      measurements.
AB  - In this paper we describe a preliminary modeling and analysis of a unique data
      set comprising unobtrusive and continuous measurements of gait velocity in the
      elder participants' residences. The data have been collected as a part of a
      longitudinal study aimed at early detection of cognitive decline. We motivate
      these analyses by first presenting evidence that suggests significant
      relationship between gait parameters and cognitive functions. We then describe a
      simple, model-based approach to the analysis of gait velocity using a weighted
      correlation function estimates. One of the main challenges is due to the fact
      that the daily estimates of the gait parameters vary with the number of walks. We
      illustrate the importance of using weighted as opposed to unweighted estimates on
      a sample of different houses. The correlation functions appear to capture
      behavioral differences that can be related to the cognitive functioning of the
      participants.

PMID- 21096045
TI  - Models of cognitive performance based on home monitoring data.
AB  - Modeling cognitive performance using home monitoring data is a new approach to
      managing neurologic conditions and for monitoring the effects of cognitive
      exercise interventions. The data consists of activity monitoring from motion
      sensors and specific cognitive metrics embedded within our adaptive computer
      games. The frequency and continuity of data collection allows us to analyze
      within subject trends of cognitive performance and to assess day to day
      variability. This approach provides a framework for clinicians and care managers
      to have the potential of detecting patients' cognitive problems early and to have
      timely feedback on treatment interventions.

PMID- 21096046
TI  - Cognitive performance modeling based on general systems performance theory.
AB  - General Systems Performance Theory (GSPT) was initially motivated by problems
      associated with quantifying different aspects of human performance. It has proved
      to be invaluable for measurement development and understanding quantitative
      relationships between human subsystem capacities and performance in complex
      tasks. It is now desired to bring focus to the application of GSPT to modeling of
      cognitive system performance. Previous studies involving two complex tasks (i.e.,
      driving and performing laparoscopic surgery) and incorporating measures that are
      clearly related to cognitive performance (information processing speed and short
      term memory capacity) were revisited. A GSPT-derived method of task analysis and
      performance prediction termed Nonlinear Causal Resource Analysis (NCRA) was
      employed to determine the demand on basic cognitive performance resources
      required to support different levels of complex task performance. This approach
      is presented as a means to determine a cognitive workload profile and the
      subsequent computation of a single number measure of cognitive workload (CW).
      Computation of CW may be a viable alternative to measuring it. Various possible
      "more basic" performance resources that contribute to cognitive system
      performance are discussed. It is concluded from this preliminary exploration that
      a GSPT-based approach can contribute to defining cognitive performance models
      that are useful for both individual subjects and specific groups (e.g., military
      pilots).

PMID- 21096047
TI  - Arm path fragmentation and spatiotemporal features of hand reaching in healthy
      subjects and stroke patients.
AB  - Arm motion in healthy humans is characterized by smooth and relatively short
      paths. The current study focused on 3D reaching in stroke patients. Sixteen right
      hemiparetic stroke patients and 8 healthy adults performed 42 reaching movements
      towards 3 visual targets located at an extended arm distance. Performance was
      assessed in terms of spatial and temporal features of the movement; i.e., hand
      path, arm posture and smoothness. Differences between groups and within subjects
      were hypothesized for spatial and temporal aspects of reaching under the
      assumption that both are independent. As expected, upper limb motion of patients
      was characterized by longer and jerkier hand paths and slower speeds. Assessment
      of the number of sub-movements within each movement did not clearly discriminate
      between groups. Principal component analyses revealed specific clusters of either
      spatial or temporal measures, which accounted for a large proportion of the
      variance in patients but not in healthy controls. These findings support the
      notion of a separation between spatial and temporal features of movement. Stroke
      patients may fail to integrate the two aspects when executing reaching movements
      towards visual targets.

PMID- 21096048
TI  - Human strategies in balancing an inverted pendulum with time delay.
AB  - The strategy of human manual control is investigated in balancing an inverted
      pendulum under time-delay constraints. Experiments show that as the task becomes
      more difficult due to the increase in time delay, the human operator adopts a
      more discrete-like strategy. Interpretation of the discrete-control mechanism is
      provided by relating the observed human responses with a human-performance model.

PMID- 21096049
TI  - Wireless control of smartphones with tongue motion using tongue drive assistive
      technology.
AB  - Tongue Drive System (TDS) is a noninvasive, wireless and wearable assistive
      technology that helps people with severe disabilities control their environments
      using their tongue motion. TDS translates specific tongue gestures to commands by
      detecting a small permanent magnetic tracer on the users' tongue. We have linked
      the TDS to a smartphone (iPhone/iPod Touch) with a customized wireless module,
      added to the iPhone. We also migrated and ran the TDS sensor signal processing
      algorithm and graphical user interface on the iPhone in real time. The TDS-iPhone
      interface was evaluated by four able- bodied subjects for dialing 10-digit phone
      numbers using the standard telephone keypad and three methods of prompting the
      numbers: visual, auditory, and cognitive. Preliminary results showed that the
      interface worked quite reliably at a rate of 15.4 digits per minute, on average,
      with negligible errors.

PMID- 21096050
TI  - Wireless fabric patch sensors for wearable healthcare.
AB  - Two novel wireless fabric patch sensors are introduced for low energy wearable
      healthcare. The first is a wirelessly powered patch sensor that can be attached
      to a patient to capture electrocardiogram (ECG) while consuming only 12 microW.
      By using fabric circuit board technology, the band-aid like sensor is
      implemented. The second wearable cardiac heathcare sensor, fabricated in the form
      of 4-layer compact smart poultice type including flexible battery, can extend to
      monitor bio-impedance together with ECG signals at 16 different sites of the
      heart with 25 reconfigurable electrodes. It also provides cm-range inductive
      coupled remote system start-up and duty-cycled data transmission using body as
      communication channel for a low energy wireless interconnectivity. Both sensors
      exploit dry fabric electrodes to minimize skin irritation during clinical long
      term operation.

PMID- 21096052
TI  - A low-power asynchronous ECG acquisition system in CMOS technology.
AB  - An asynchronous electrocardiogram (ECG) acquisition system is presented for
      wearable ambulatory monitoring. The proposed system consists of a low noise front
      end amplifier (AFE) with tunable bandwidth, an asynchronous analog-to-digital
      converter (ADC), and digital signal processing (DSP). Data compression is
      achieved by the inherent signal dependent sampling rate of the asynchronous
      architecture. This makes the system attractive for compact wearable ECG
      monitoring applications. The AFE and ADC were fabricated in a 0.18 microm CMOS
      technology and consume a total of 79 microW. Measured results demonstrating ECG
      monitoring are presented.

PMID- 21096051
TI  - Development of a sleep apnea event detection method using photoplethysmography.
AB  - We studied the possibility of detection of sleep apnea or hypopnea events from
      photoplethysmography (PPG) wave variation patterns during sleep. In three
      patients with suspected sleep apnea syndrome, polysomnography (PSG) and the PPG
      wave were measured simultaneously during sleep. The characteristics of the PPG
      wave variation patterns in apnea or hypopnea events detected by PSG were
      investigated. It was found that pulse rate increases and pulse wave amplitude
      decreases during apnea or hypopnea events, and the respiratory component of heart
      rate variability has a tendency to decrease before the apnea or hypopnea events.
      Also, compared to hypopnea, the ratio of the pulse rate is higher, the reduction
      of the pulse amplitude is more significant, and the decrease of the degree of
      respiratory variation component in the apnea event is greater. We devised the
      apnea / hypopnea detection algorithm using these characteristics and evaluated
      its effectiveness.

PMID- 21096053
TI  - Care assessment platform: an ICT-enabled home care model for secondary prevention
      of cardiovascular diseases.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading chronic diseases
      affecting developed countries. Traditional approach to secondary prevention of
      CVD through hospital-based cardiac rehabilitation (CR) is hampered by the lack of
      uptake and adherence.

PMID- 21096054
TI  - Telehealth technologies for managing chronic disease - experiences from Australia
      and the UK.
AB  - In developed countries, chronic disease now accounts for more than 75% of health
      care expenditure and nearly an equivalent percentage of disease-related deaths
      [1]. The burden of chronic disease (often, but not exclusively, associated with
      ageing) includes congestive heart failure (CHF), chronic obstructive pulmonary
      disease (COPD), hypertension and diabetes. Over the past several decades there
      has been an epidemiological shift in disease burden from acute to chronic
      diseases that has rendered acute care models of health service delivery
      inadequate to address population health needs.

PMID- 21096055
TI  - A diabetes management system empowering patients to reach optimised glucose
      control: from monitor to advisor.
AB  - The DIAdvisor is an EC/FP7 funded project aiming at the development of a Blood
      Glucose prediction device which uses easily available information to optimise the
      therapy of patients with diabetes.

PMID- 21096056
TI  - Personal health systems - Opportunities and barriers for adoption.
AB  - INCREASING prevalence of lifestyle-related health risks and chronic diseases,
      coupled with limited resources in the healthcare system, calls for citizen
      centric health promotion and disease prevention measures as well as new care
      models for management of chronic diseases. As a future scenario emphasis of the
      health care should gradually shift from treating and managing of diseases to
      their prevention and early interventions. The risk of chronic diseases begins to
      rise and physical capacity begins to decline after the age of 30. Therefore,
      working-age citizens are an important target group for health promotion and early
      interventions.

PMID- 21096057
TI  - Hidden state dynamics in laser Doppler vibrometery measurements of the carotid
      pulse under resting conditions.
AB  - A laser Doppler vibrometer (LDV) is used to sense movements of the skin overlying
      the carotid artery. Fluctuations in carotid artery diameter due to variations in
      the underlying blood pressure are sensed at the surface of the skin. Portions of
      the LDV signal corresponding to single heartbeats, called the LDV pulses, are
      extracted. This paper introduces the use of hidden Markov models (HMMs) to model
      the dynamics of the LDV pulse from beat to beat based on pulse morphology, which
      under resting conditions are primarily due to breathing effects. LDV pulses are
      classified according to state, by computing the optimal state path through the
      data using trained HMMs. HMM state dynamics are compared to simultaneous
      recordings of strain gauges placed on the abdomen. The work presented here
      provides a robust statistical approach to modeling the dependence of the LDV
      pulse on latent states.

PMID- 21096058
TI  - Pulse wave velocity in patients with severe head injury a pilot study.
AB  - The study aimed to determine the potential of pulse wave velocity measurements to
      reflect changes in compliant cerebral arteries/arterioles in head injured
      patients. The approach utilizes the electrocardiogram and intracranial pressure
      signals to measure the wave transit time between heart and cranial cavity. Thirty
      five clinical records of nineteen head injured patients, with different levels of
      cerebrovascular pressure-reactivity response, were investigated through the
      study. Results were compared with magnitude of normalized transfer function at
      the fundamental cardiac frequency. In patients with intact cerebrovascular
      pressure-reactivity, magnitude of normalized transfer function at the fundamental
      cardiac component was found to be highly correlated with pulse wave transit time.

PMID- 21096059
TI  - Relative blood volume monitoring during hemodialysis in end stage renal disease
      patients.
AB  - A crucial point in the haemodialysis (HD) treatment is the reliable assessment of
      hydration status. An inadequate removed volume may lead to chronic fluid overload
      which can lead to hypertension, left ventricular hypertrophy and heart failure.
      Therefore, the estimation of the hydration state and the management of a well
      tolerated water removal is an important challenge. This exploratory study aims at
      identifying new parameters obtained from continuous Blood Volume Monitoring (BVM)
      allowing a qualitative evaluation of hydration status for verifying the adequacy
      of HD setting parameters (e.g UFR, target dry weight). The percentage of blood
      volume reduction (BVR%) during HD was compared against a gold standard method for
      hydration status assessment. The slope of the first 30 minute of blood volume
      reduction (BVR) was proposed as a useful parameter to identify overhydrated
      patients.

PMID- 21096060
TI  - Atrial fibrillation disorganization is reduced by catheter ablation: a standard
      ECG study.
AB  - Selection of candidates to catheter ablation (CA) of long-lasting persistent
      atrial fibrillation (AF) is challenging, since success is not guaranteed. In this
      study, we put forward an automated method for noninvasively evaluating the
      reduction of the complexity of the AF organization following CA. Complexity is
      meant as the amount of disorganization observed on the ECG, supposed to be
      directly correlated to the number and interactions of atrial wavefronts. By means
      of PCA, the complexity of the AF organization is evaluated quantitatively from a
      12-lead ECG recording. Preliminary results show that CA is able to reduce the
      complexity of AF organization in the atrial wavefront pattern propagation,
      despite the persistence of AF in most cases. This can be viewed as a first
      clinical validation of this parameter. Whether AF complexity and its reduction by
      CA are predictive of long-term outcome is thus still to be determined.

PMID- 21096061
TI  - Visualizing the electrocardiogram through orbital transform.
AB  - The purpose of this work is to present a new electrocardiogram (ECG)
      visualization technique through a mathematical transform applied to one lead ECG
      signal. This transform, called orbital transform (OT) in this work, consists of a
      remapping of the ECG signal to a spatial curve represented by a three dimensional
      phase portrait. With this spatial curve it is possible to observe the evolution
      of changes in the QRS complex, which are not always clear to distinguish by a
      simple visual inspection of the temporal ECG signal. Moreover, using the
      projection of this curve in one of the 2D planes it is possible to easily
      calculate variation ranges of several ECG parameters such as maximal and minimal
      waves amplitudes and maximal and minimal wave slopes.

PMID- 21096062
TI  - Relationship between heart rate variability using Lorenz plot and sleep level.
AB  - In the present study, we propose a new technique for estimating depth of sleep
      over the whole night using electrocardiogram (ECG) RR intervals (RRIs). We
      produced a Lorenz plot (LP) using the RRIs recorded during all-night sleep and
      confirmed that changes in distribution on the LP occur based on changes in sleep
      stage. To evaluate the changes in these distributions, RRIs are projected a LP on
      a y = x axis, y = -x axis, and analyzed the shifting of the mean (center C) and
      standard deviation (area S) for each sleep stage. Analysis interval time was 60
      seconds, shifting every second, and we compared heart rate variability (HRV) and
      sleep level. Center C showed progress toward light sleep levels and area S showed
      the transition phases toward deep sleep. A concordance rate of 60.1% between the
      estimated values and actual transitional sleep level was obtained for all-night
      sleep. Therefore, transitional sleep level can be evaluated based on HRV using
      the LP.

PMID- 21096063
TI  - High range resolution medical acoustic vascular imaging with frequency domain
      interferometry.
AB  - For high range resolution acoustic vascular imaging we apply frequency domain
      interferometry and Capon method to a few frames of in-phase and quadrature (IQ)
      data acquired by a commercial ultrasonographic device. To suit the adaptive
      beamforming algorithm to medical acoustic imaging we employ three techniques;
      frequency averaging, whitening, and pseudo-double RF data conversion. The
      proposed method detected two couples of boundaries 0.26 and 0.19 mm apart using a
      single frame and two frames of IQ data, respectively, where each couple of
      boundaries is indistinguishable from a single boundary utilizing B-mode images.
      Further this algorithm could depict a swine femoral artery with higher range
      resolution than conventional B-mode imaging. These results indicate the potential
      of the proposed method for the range resolution improvement in ultrasonography,
      originating the progress in detection of vessel stenosis.

PMID- 21096064
TI  - Understanding the vascular environment of myofascial trigger points using
      ultrasonic imaging and computational modeling.
AB  - Myofascial pain syndrome (MPS) is a common, yet poorly understood, acute and
      chronic pain condition. MPS is characterized by local and referred pain
      associated with hyperirritable nodules known as myofascial trigger points (MTrPs)
      that are stiff, localized spots of exquisite tenderness in a palpable taut band
      of skeletal muscle. Recently, our research group has developed new ultrasound
      imaging methods to visualize and characterize MTrPs and their surrounding soft
      tissue. The goal of this paper was to quantitatively analyze Doppler velocity
      waveforms in blood vessels in the neighborhood of MTrPs to characterize their
      vascular environment. A lumped parameter compartment model was then used to
      understand the physiological origin of the flow velocity waveforms. 16 patients
      with acute neck pain were recruited for the study and the blood vessels in the
      upper trapezius muscle in the neighborhood of palpable MTrPs were imaged using
      Doppler ultrasound. Preliminary findings show that symptomatic MTrPs have
      significantly higher peak systolic velocities and negative diastolic velocities
      compared to latent MTrPs and normal muscle sites. Using compartment modeling, we
      show that a constricted vascular bed and an enlarged vascular volume could
      explain the observed flow waveforms with retrograde diastolic flow.

PMID- 21096065
TI  - Non-invasive hemodynamic state monitoring using ultrasound.
AB  - Hemodynamic monitoring provides vital information for diagnosing and treating
      patients in acute clinical settings. A method is investigated to non-invasively
      monitor changes in the hemodynamic state. The approach utilizes short-axis
      ultrasound color flow imaging and processing methods to produce simultaneous
      waveforms for the arterial area and flow. Beat-to-beat measurements of the mean
      area, peak volumetric flow rate, and heart rate are extracted, and the
      distribution of these parameters is used to define the hemodynamic state. Changes
      in the hemodynamic state are detected by calculating a distance between new
      measurements and the current hemodynamic state, and then comparing this distance
      to an adaptive threshold. The distribution was modeled as a multivariate normal
      distribution characterized by a mean vector and a covariance matrix, and the
      Mahalanobis distance was used as the distance metric. The threshold level was
      adapted to produce a constant probability of false positives based on the current
      distribution. The method was evaluated by observing pharmacologically induced
      changes in the hemodynamic state during an in vivo animal experiment. The
      ultrasound-based measurements provided sufficient accuracy to discriminate
      between the hemodynamic states before, during and after infusion of a
      vasodilator. The ability to detect an acute change in the hemodynamic state was
      demonstrated in the transient period at the start of the infusion.

PMID- 21096066
TI  - Measurement of tendon velocities using vector tissue Doppler imaging: a
      feasibility study.
AB  - We have developed a vector Doppler ultrasound imaging method to directly quantify
      the magnitude and direction of muscle and tendon velocities during movement. The
      goal of this study was to evaluate the feasibility of using vector Tissue Doppler
      Imaging (vTDI) for estimating the tibialis anterior tendon velocities during
      dorsiflexion in children with cerebral palsy who have foot drop. Our preliminary
      results from this study show that tendon velocities estimated using vTDI have a
      strong linear correlation with the joint angular velocity estimated using a
      conventional 3D motion capture system. We observed a peak tendon velocity of
      5.66+/-1.45 cm/s during dorsiflexion and a peak velocity of 8.83+/-2.13 cm/s
      during the passive relaxation phase of movement. We also obtained repeatable
      results from the same subject 3 weeks apart. Direct measurements of muscle and
      tendon velocities may be used as clinical outcome measures and for studying
      efficiency of movement control.

PMID- 21096067
TI  - Separation of preterm infection model from normal pregnancy in mice using texture
      analysis of second harmonic generation images.
AB  - This paper presents an image processing system to distinguish a
      lipopolysaccharide (LPS) infection model of preterm labor from normal mouse
      pregnancy using Second Harmonic Generation (SHG) images of mouse cervix. Two
      classes of SHG images are considered: images from mice in which premature birth
      was caused by intrauterine LPS administration and images from normal pregnant
      mice. A wide collection of image texture features consisting of co-occurrence
      matrix-based, granulometry-based and wavelet-based are examined. The results
      obtained indicate that the combination of co-occurrence-based and granulometry
      based textures features provides the most effective texture set for separating
      these two classes of images.

PMID- 21096068
TI  - Probing protein binding spectra with Fourier microfluidics.
AB  - New developments in microfluidic chip technology enable the construction of
      chemical spectrum analyzers that can probe the binding interactions between
      chemical entities. In this paper we report the implementation of a microfluidic
      chip suitable for Fourier transform measurements of biochemical interactions. The
      chip consists of a chemical signal generator, a flow cell and a binding sensor
      surface. The microfluidic signal generator produces a periodic stream of protein
      plugs in solution flowing at constant velocity through the cell. This flow
      produces periodic association and dissociation cycles of the protein to a
      functionalized gold sensing surface placed inside the cell. The sensor activity
      corresponding to the phasor response of the chemical interaction at the
      excitation frequency is measured optically using surface plasmon resonance (SPR)
      imaging. We demonstrated the feasibility of the technique using a model system of
      carbonic anhydrase-II (CA-II) and immobilized 4-(2-Aminoethyl) benzenesulfonamide
      (ABS) ligand. The observed transfer function showed a dominant pole at 10.2 mHz
      corresponding to association and dissociation constants of 4.8 * 10(3) M(-1).s(
      1), and 3.5 * 10(-2) s(-1) respectively.

PMID- 21096069
TI  - A miniaturized device for wireless FSCV monitoring of dopamine in an ambulatory
      subject.
AB  - This paper reports on a miniaturized device for wireless monitoring of
      extracellular dopamine levels in the brain of an ambulatory rat using fast-scan
      cyclic voltammetry at a carbon-fiber microelectrode. The device comprises
      integrated circuitry for neurochemical recording fabricated in 0.5-microm double
      poly triple-metal CMOS technology, which is assembled and packaged on a miniature
      rigid-flex substrate together with a few external components for supply
      generation, biasing, and chip programming. The device operates from a single 3-V
      battery, weighs 2.3 g (including the battery), and upon implantation successfully
      captures the effects of the psychostimulant amphetamine on electrically and non
      electrically evoked dopamine neurotransmission in the caudateputamen region of an
      ambulatory rat's forebrain.

PMID- 21096070
TI  - A novel pulse-based modulation technique for wideband low power communication
      with neuroprosthetic devices.
AB  - Pulse Harmonic Modulation (PHM) is a novel pulse-based (carrierless) modulation
      method for wideband, low power data transmission across inductive telemetry links
      that operate in the near-field domain. PHM utilizes two or more unidentical
      pulses during each bit period to minimize inter-symbol interference (ISI). In
      this paper, we describe the PHM concept and demonstrate its operation with a
      proof-of-concept prototype, which achieves a data rate of 5.2 Mbps at 1 cm coil
      separation with a bit error rate (BER) of 10(-6).

PMID- 21096071
TI  - Microsystems technology in radiation therapy.
AB  - In this paper, we present several implantable micro-devices targeted towards
      improving the efficacy of radiation therapy. Three micro-devices are discussed: a
      self-biased solid state dosimeter to be used for wireless monitoring of the
      delivered dose, an electromagnetic tracking system to locate the position of
      tumor in real-time, and a Guyton-chamber-embedded capacitive pressure sensor for
      wireless measurement of interstitial pressure inside a tumor. Dosimeter and
      tracking systems are developed to be integrated together to achieve a track-able
      radiation sensor. Guyton chamber of the pressure sensor will eliminate the sensor
      drift due to the interaction of cells and fibrous tissue with sensor's membrane.
      The dosimeter has a sensitivity of up to 9 kOmega/Gy and a dynamic range of 10
      Gy, when operating with a zero bias voltage. The tracking system is able to track
      a tumor that is 60 cm away with a resolution of 2 mm and a dynamic range of up to
      5 cm. Finally, the capacitive pressure sensor has a sensitivity of 75 fF/kPa and
      a dynamic range of 60 mmHg.

PMID- 21096072
TI  - Segmenting the sepal and shoot apical meristem of Arabidopsis thaliana.
AB  - We present methods for segmenting the sepal and shoot apical meristem of the
      Arabidopsis thaliana plant. We propose a mathematical morphology pipeline and a
      modified numerical scheme for the active contours without edges algorithm to
      extract the geometry and topology of plant cells imaged using confocal laser
      scanning microscopy. We demonstrate our methods in typical images used in the
      studies of cell endoreduplication and hormone transport and show that in practice
      they produce highly accurate results requiring little human intervention to cope
      with image aberrations.

PMID- 21096073
TI  - Comparison of source separation techniques for multilead T-wave alternans
      detection in the ECG.
AB  - T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms
      leading to sudden cardiac death. In this work, we evaluate different source
      separation techniques for multilead detection of TWA in the electrocardiogram
      (ECG). Two periodicity-based techniques - periodic component analysis (piCA) and
      the newly proposed spectral ratio maximization (SRM) - are compared to two
      independence-based techniques - FastICA and JADE - and to principal component
      analysis (PCA). According to simulation results, the best detection performance
      is obtained with the periodicity-based schemes.

PMID- 21096074
TI  - Skin relaxation predicts neural firing rate adaptation in SAI touch receptors.
AB  - In response to ramp-and-hold indentation, the slowly-adapting type I (SAI)
      afferent exhibits an exponential decrease in its firing frequency during the hold
      phase. Such adaptation may be tied to skin relaxation but is neither well
      understood nor has it been quantitatively modeled. The specific hypothesis of
      this work is that skin relaxation is a primary contributor to observed changes in
      firing rate. Double exponential functions were fit to 21 responses from a mouse
      SAI afferent for both instantaneous firing rate and indenter tip force over time.
      The model was then generalized by using a linear transformation between fit
      parameters for force and firing rate data, allowing prediction of firing rates
      from force. The results show that the generalized model matches the recorded
      firing rate (R(2) = 0.65) equally well as fitting a doubleexponential function
      directly to firing rate (R(2) = 0.67) for a second dataset. When the procedure
      was repeated with two D-hair fibers, the generalized model matched the recorded
      firing rate (R(2) = 0.47) much more poorly compared to the fitted double
      exponential function (R(2) = 0.89). Thus, firing rate adaptation in SAI responses
      can be predicted by skin relaxation, whereas this factor alone did not adequately
      describe adaptation in the D-hair.

PMID- 21096075
TI  - Non-listening effort related parameters in auditory discrimination paradigms.
AB  - Objective methods to asses listening effort are still missing in clinical
      settings. Thus, the focus of our ongoing research is the extraction of possible
      substrates of listening effort. This paper focuses on the non-effort related
      factor reaction time (RT) on the different components of auditory late responses
      (ALRs). It makes sense to consider this factor in the context of age related
      changes of the RT. For the comparison of the ALR components and the RT, two
      syllable oddball paradigms with different degree of difficulty were created. The
      paradigms were embedded in multitalker babble noise to create a realistic
      listening situation. The data was collected from 13 normal hearing healthy
      subjects, who had to detect a deviant. Furthermore, the wavelet phase
      synchronization stability (WPSS) was calculated for different scales. A filter
      bank was designed in order to separate the components by their frequency content.
      Finally, the Pearson product-moment correlation coefficient was calculated to
      clarify if there is a possible linkage between the RT and the ALR components. The
      results show, that only the P(3) latency is correlated with the RT. A relation
      between the RT and the other ALR components could not be observed. It is
      concluded, that the focus of our further research, will be on the N(1) and the
      P(2) wave due to the fact that those components are independent from the non-
      effort related factor reaction time.

PMID- 21096076
TI  - ZMIND - an interactive environment for electrical modeling of the thorax.
AB  - Interest in the electrical modeling of the thorax is motivated by various desires
      ranging from determining cardiac function, optimizing defibrillation efficacy,
      monitoring pulmonary edema, etc. However, existing models represent the thorax
      with rather coarse anatomical details, limiting their utilizations for accurately
      simulating small electrodes which typically occurs in pacing and defibrillation
      clinical practices. In this paper, we describe an anatomically realistic finite
      difference modeling software environment, referred as ZMIND. Segmented image
      based finite difference models of a male adult at the end of systole and the end
      of diastole were constructed based on ECG-gated MRI scans. Up to 36 types of
      tissues were identified and included in the model, providing fine anatomical
      details in the heart and lung regions. The environment enables placing electrodes
      interactively and also provides a library of clinically-based, user-configurable
      electrodes. The analysis module of this environment allows performing sensitivity
      analysis and visualizing the computed electric fields, current density, and
      sensitivity distribution.

PMID- 21096077
TI  - Using the Virtual Heart Model to validate the mode-switch pacemaker operation.
AB  - Artificial pacemakers are one of the most widely-used implantable devices today,
      with millions implanted worldwide. The main purpose of an artificial pacemaker is
      to treat bradycardia, or slow heart beats, by pacing the atrium and ventricles at
      a faster rate. While the basic functionality of the device is fairly simple,
      there are many documented cases of death and injury due to device malfunctions.
      The frequency of malfunctions due to firmware problems will only increase as the
      pacemaker operations become more complex in an attempt to expand the use of the
      device. One reason these malfunctions arise is that there is currently no
      methodology for formal validation and verification of medical device software, as
      there are in the safety-critical domains of avionics and industrial control
      automation. We have developed a timed-automata based Virtual Heart Model (VHM) to
      act as platform for medical device software validation and verification. Through
      a case study involving multiple arrhythmias, this investigation shows how the VHM
      can be used with closed-loop operation of a pacemaker to validate the necessity
      and functionality of the complex mode-switch pacemaker operation. We demonstrate
      the correct pacemaker operation, to switch from one rhythm management mode to
      another, in patients with supraventricular tachycardias. (1).

PMID- 21096078
TI  - Suitable acoustic paths to transfer energy in depth using ultrasound.
AB  - The goal of this study is to optimize the transfer of acoustic energy deep in the
      body. In order to find suitable acoustic paths for the energy transfer to be
      efficient, we propose a model of ultrasound propagation that takes into account a
      realistic geometry of the tissue layers inside the human body. The data from the
      Visible Human Project is used to identify the tissues between the transducer
      array and the target point located on the epicard of the heart. The model is
      validated by comparison with measurements of the pressure field radiated by a
      focused 64-element array in water. Then, model results are presented in a
      realistic configuration, choosing a suitable input acoustic power so that adverse
      bio-effects are minimized. The model predicts the amount of acoustic energy that
      can be obtained at the target point, and is therefore useful to select the best
      acoustic path among several possibilities.

PMID- 21096079
TI  - Design of a fuzzy controller for the automation of an extracorporeal support
      system with the use of a simulation environment.
AB  - The automation of a portable extracorporeal support system may greatly help
      people who suffer from cardiogenic shock by providing them with an optimal oxygen
      perfusion and avoid mult-organ failure while being transported to a hospital.
      This however requires the creation of tools that help in the design of the ideal
      controller. In this paper a simulation environment is described were a
      cardiovascular model from the ISR Physiome database was used together with a
      model of a portable extracorporeal support system. Additionally a model of an
      oxygenator/blender model is introduced to allow the simulation of oxygen
      perfusion. Fuzzy controlling was used for automation since it allows a
      straightforward implementation of expert knowledge. Through the simulation
      environment different scenarios may be created where intensive testing is
      possible and constant repetition for control optimization. Initial simulation
      results are given of the fuzzy controller adjusting the extracorporeal flow rate
      and oxygen administration for a case of low cardiac output.

PMID- 21096080
TI  - Safety evaluation of magnetic catheter steering with upgraded magnetic resonance
      imaging system.
AB  - Catheter navigation and placement through the arterial network is a major
      limitation for clinical procedure. In this article, a specific catheter tip and a
      modified clinical MRI scanner with an upgraded gradient system are used to steer
      a catheter through a single Y-shaped bifurcation. Safety aspects are analyzed to
      avoid the peripheral nerve stimulation (PNS) according to an empirical law of
      magnetostimulation and the magnetic field of upgraded 3D gradient coils. For a
      rabbit-sized device, the rising time of gradients system have to be limited to
      1.7ms at 400mT.m(-1) to avoid PNS. These rise time values allow the use of this
      system for catheter steering and other more demanding applications.

PMID- 21096081
TI  - Characteristics of smooth muscle cells' shape and proliferation rate in novel
      short-term thermal angioplasty ex vivo and in vitro.
AB  - We investigated the influences on the smooth muscle cells of temporally heated
      arterial walls in both ex vivo and in vitro study to determine the optimum heat
      parameter of novel short-term thermal angioplasty, Photo-thermo Dynamic Balloon
      Angioplasty (PTDBA). Arterial heating dilatation was performed by the prototype
      PTDBA balloon ex vivo. We found that the smooth muscle cells in the vessel wall
      were stretch-fixed after the heating dilatation ex vivo. The stretch-fixing rate
      of these cells was increased with the temperature rise in the balloon of PTDBA
      from 60  degrees C to 70  degrees C. We measured the proliferation rate of the
      stretch-fixed smooth muscle cells, which were extracted from porcine arteries, on
      specially designed culture equipment in vitro. It was observed that the
      proliferation rate was inhibited at 20 % stretching compared to 10 % stretching.
      We think the stretch-fixing of the smooth muscle cells might not be harmful for
      PTDBA performances.

PMID- 21096082
TI  - Delineation and interpretation of gene networks towards their effect in cellular
      physiology- a reverse engineering approach for the identification of critical
      molecular players, through the use of ontologies.
AB  - Exploiting ontologies, provides clues regarding the involvement of certain
      molecular processes in the cellular phenotypic manifestation. However,
      identifying individual molecular actors (genes, proteins, etc.) for targeted
      biological validation in a generic, prioritized, fashion, based in objective
      measures of their effects in the cellular physiology, remains a challenge. In
      this work, a new meta-analysis algorithm is proposed for the holistic
      interpretation of the information captured in -omic experiments, that is
      showcased in a transcriptomic, dynamic, DNA microarray dataset, which examines
      the effect of mastic oil treatment in Lewis lung carcinoma cells. Through the use
      of the Gene Ontology this algorithm relates genes to specific cellular pathways
      and vice versa in order to further reverse engineer the critical role of specific
      genes, starting from the results of various statistical enrichment analyses. The
      algorithm is able to discriminate candidate hub-genes, implying critical
      biochemical cross-talk. Moreover, performance measures of the algorithm are
      derived, when evaluated with respect to the differential expression gene list of
      the dataset.

PMID- 21096083
TI  - A hybrid Decision Support System for the risk assessment of retinopathy
      development as a long term complication of Type 1 Diabetes Mellitus.
AB  - The aim of the present study is to design and develop a Decision Support System
      (DSS) closely coupled with an Electronic Medical Record (EMR), able to predict
      the risk of a Type 1 Diabetes Mellitus (T1DM) patient to develop retinopathy. The
      proposed system is able to store a wealth of information regarding the clinical
      state of the T1DM patient and continuously provide the health experts with
      predictions regarding the possible future complications that he may present. The
      DSS is a hybrid infrastructure combining a Feedforward Neural Network (FNN), a
      Classification and Regression Tree (CART) and a Rule Induction C5.0 classifier,
      with an improved Hybrid Wavelet Neural Network (iHWNN). A voting mechanism is
      utilized to merge the results from the four classification models. The proposed
      DSS has been trained and evaluated using data from 55 T1DM patients, acquired by
      the Athens Hippokration Hospital in close collaboration with the EURODIAB
      research team. The DSS has shown an excellent performance resulting in an
      accuracy of 98%. Care has been taken to design and implement a consistent and
      continuously evolving Information Technology (IT) system by utilizing
      technologies such as smart agents periodically triggered to retrain the DSS with
      new cases added in the data repository.

PMID- 21096084
TI  - Construction of signaling pathways and identification of drug effects on the
      liver cancer cell HepG2.
AB  - Construction of signaling pathway maps and identification of drug effects are
      major challenge for pharmaceutical industries. Signaling maps are usually
      obtained from manual literature search, automated text mining algorithms, or
      canonical pathway databases (i.e. Reactome, KEGG, STKE, Pathway Studio, Ingenuity
      etc.) and in some cases they are used in combination with gene expression or mass
      spec data in an effort to create pathways specific to cell types or diseases. Our
      approach combines computational models with novel multicombinatorial high
      throughput phosphoproteomic data for the functional analysis of signalling
      networks in mammalian cells. On the experimental front, we subject the cells with
      hundreds of co-treatment with a diverse set of ligands and inhibitors and we
      measure phosphorylation events on key signaling proteins using the xMAP
      technology. On the computational front, we create pathway maps that are cell type
      specific by fitting our phosphoprotein dataset into generic signaling maps via an
      Integer Linear programming formulation. To identify drug effects, we monitor the
      differences of topologies created with and without the presence of drug. In the
      present work, we use this approach to identify the effects of Nilotinib, a well
      known anti-cancer drug.

PMID- 21096085
TI  - Classification of dermatological images using advanced clustering techniques.
AB  - Computer vision-based diagnosis systems have been widely used in dermatology,
      aiming at the early detection of skin cancer and more specifically the
      recognition of malignant melanoma tumor. This paper proposes a novel clustering
      technique for the characterization and categorization of pigmented skin lesions
      in dermatological images. Appropriate image processing techniques (i.e.
      segmentation, border detection, color and texture processing) are utilized for
      feature extraction. The proposed method uses Principal Component Analysis and is
      considered appropriate, since it is suitable for problems with high dimensional
      data. Initial experimental results have proved the superiority of this method
      against traditional ones.

PMID- 21096086
TI  - A new curve registration technique for the analysis of T waves shapes.
AB  - T waves properties are not usually fully exploited when analyzing its profile
      variation within a set of records. An affine transform of the temporal support is
      a good candidate for the modeling of this variation. Based on this assumption, we
      propose here a new framework that provides an estimation of the reference T wave
      and the parameters of the affine functions. To achieve this task, the domain of
      the inverse normalized integral is investigated, allowing a compact description
      of the dataset. As a straightforward tool, the Principal Component Analysis is
      shown to be efficient in this do- main. This approach is illustrated by analyzing
      a set of T waves recorded during Dipyridamol infusion and during angioplasty.

PMID- 21096087
TI  - Classifier-assisted metric for chromosome pairing.
AB  - Cytogenetics plays a central role in the detection of chromosomal abnormalities
      and in the diagnosis of genetic diseases. A karyogram is an image representation
      of human chromosomes arranged in order of decreasing size and paired in 23
      classes. In this paper we propose an approach to automatically pair the
      chromosomes into a karyogram, using the information obtained in a rough SVM-based
      classification step, to help the pairing process mainly based on similarity
      metrics between the chromosomes. Using a set of geometric and band pattern
      features extracted from the chromosome images, the algorithm is formulated on a
      Bayesian framework, combining the similarity metric with the results from the
      classifier. The solution is obtained solving a mixed integer program. Two
      datasets with contrasting quality levels and 836 chromosomes each were used to
      test and validate the algorithm. Relevant improvements with respect to the
      algorithm described by the authors in [1] were obtained with average paring rates
      above 92%, close to the rates obtained by human operators.

PMID- 21096088
TI  - Adaptive extraction of emotion-related EEG segments using multidimensional
      directed information in time-frequency domain.
AB  - Emotion discrimination from electroencephalogram (EEG) has gained attention the
      last decade as a user-friendly and effective approach to EEG-based emotion
      recognition (EEG-ER) systems. Nevertheless, challenging issues regarding the
      emotion elicitation procedure, especially its effectiveness, raise. In this work,
      a novel method, which not only evaluates the degree of emotion elicitation but
      localizes the emotion information in the time-frequency domain, as well, is
      proposed. The latter, incorporates multidimensional directed information at the
      time-frequency EEG representation, extracted using empirical mode decomposition,
      and introduces an asymmetry index for adaptive emotion-related EEG segment
      selection. Experimental results derived from 16 subjects visually stimulated with
      pictures from the valence/arousal space drawn from the International Affective
      Picture System database, justify the effectiveness of the proposed approach and
      its potential contribution to the enhancement of EEG-ER systems.

PMID- 21096093
TI  - Wavelet based motion artifact removal for Functional Near Infrared Spectroscopy.
AB  - Functional Near Infrared Spectroscopy (fNIRS) enables researchers to conduct
      studies in situations where use of other functional imaging methods is
      impossible. An important shortcoming of fNIRS is the sensitivity to motion
      artifacts. We propose a new wavelet based algorithm for removing movement
      artifacts from fNIRS signals. We tested the method on simulated and experimental
      fNIRS data. The results show an average of 18.97 dB and 15.54 dB attenuation in
      motion artifacts power for our two test subjects without introducing significant
      distortion in the artifact-free regions of the signal.

PMID- 21096094
TI  - Evolution of phase synchronization of the two frequency components of the
      electrohysterogram (EHG): application to the detection of human labor.
AB  - The analysis of the electrical activity of the uterus recorded externally, the
      electrohysterogram (EHG), may find an application in the prediction of labor. In
      the literature parameters that are supposed to be related to the excitability of
      the uterine cells have almost exclusively been used for this purpose. In the
      present paper we evaluate the possible use of synchronization parameters for EHG
      measured in several places on the uterus for this prediction. The EHG is mainly
      composed of two frequency components called FWL and FWH. These components may be
      related to the synchronization and the excitability phenomenon respectively. In
      order to study independently these frequency components, we extracted the
      corresponding ridges of the wavelet transform of the EHG using the GVF-snake
      method. For each frequency component we computed parameters that are related to
      the frequency content of the signals and parameters that consider the
      synchronization relationship between signals. The synchronization parameters used
      were the mean phase coherence and the phase entropy. The values of the different
      parameters were compared during pregnancy and labor by statistical analysis. The
      detection quality of each parameter was evaluated using ROC curves. Our results
      suggest that synchronization parameters could be used for the detection of labor
      in addition to the classical previously published parameters. Another important
      result of our study is that both FWH and FWL seem related to excitability but
      only FWL seems to be related to the synchronization of the uterus at term.

PMID- 21096095
TI  - Monitor-decoupled pharmacodymamics of propofol in children using State Entropy as
      the clinical end point.
AB  - This paper presents two alternative approaches to characterize the
      pharmacodynamics of propofol anesthesia in children, using State Entropy as a
      clinical end point. The first approach is the traditional approach where the
      pharmacodynamic model is described in terms of an effect-site equilibration rate
      constant and the Hill equation. In the second approach (the monitor-decoupled
      approach) the dynamics of the Entropy monitor is identified and added to the
      traditional pharmacodynamic model. The traditional approach resulted in mean
      k(e0) values of 2.08min(-1) and 1.27min(-1) for the Paedfusor and Kataria
      pharmacokinetic models, respectively. The monitor-decoupled approach resulted in
      significantly larger values (mean k(e0) values of 2.57min(-1) and 1.71min(-1))
      than the traditional approach. The differences between k(e0) values suggest that
      the dynamic effect of the Entropy monitor must be accounted for when identifying
      the "true" pharmacodynamics of the patient, without the bias caused by the
      monitor's processing characteristics. The values of k(e0) obtained in this study
      were larger than those values previously published for the Bispectral Index. This
      is likely due to the different processing characteristics of the Entropy and
      Bispectral Index monitors, as well as the use of different pharmacokinetic
      models.

PMID- 21096096
TI  - Circuit analysis justifies a reduced Mead's model of the human respiratory
      impedance for impulse oscillometry data.
AB  - Recent attempts at estimating the parameters for respiratory impedance models
      from data obtained by Impulse Oscillometry (IOS) have come across difficulties
      when using the well-established Mead's model of human respiratory impedance.
      Unconstrained optimization of this model often yields values of chest wall
      compliance (C(W)) and lung compliance (C(l)) too large to be physiologically
      feasible. We hypothesize that IOS volume displacements are inconsequential to the
      lung tissue and chest wall due to the small contributions of these displacements
      relative to lung capacity. In order to explore the validity of this hypothesis we
      performed a detailed analysis of Mead's impedance model. The IOS input flow
      signal was approximated by using a combination of typical waveforms, this signal
      was then used to excite Mead's electrical circuit model of the respiratory
      impedance with physiologically realistic parameter values estimated using data
      obtained from one normal adult, ten adult patients with Cystic Fibrosis, ten
      patients with Asthma and ten normal children, with focus on normal adult data.
      Pressure waveforms, energy and integrated pressure values were then obtained and
      compared at different points of interest in the model. This investigation
      suggests that the pressures "felt" by the lung tissue and chest wall are too
      small to have a noticeable effect on them therefore making those particular
      circuit elements unnecessary when the respiratory system is subject to small
      displacement volumes such as those used in Impulse Oscillometry. Furthermore, we
      believe that the very large parameter values often obtained with unconstrained
      optimization of Mead's model are evidence that C(l) and C(w) could be "shorted
      out" when modeling IOS data.

PMID- 21096097
TI  - Viability of the inner retina in a novel mouse model of retinitis pigmentosa.
AB  - Retinal prostheses aim to restore vision to patients who are blind from
      photoreceptor diseases such as Retinitis Pigmentosa (RP). All implants target the
      neural cells in the inner retina, the retinal ganglion cells (RGCs). Our research
      focuses on further understanding the disease process of RP during mid to late
      stages when total loss of photoreceptors has occurred and significant remodeling
      of inner retinal neurons has taken place. We have used a novel transgenic mouse,
      Rd1-FTL, to observe different degenerative stages of RP. Notably, in the aged
      retina we have evidence that there was gross inner retinal remodeling as well as
      glial dysfunction that occurred in confined regions in the central retina that
      worsened overtime. Consequently, the timing of implantation and location of the
      prosthesis both need to account for the state of the retina at different stages
      in the disease process.

PMID- 21096098
TI  - SAR analysis of a re-entrant resonant cavity applicator for brain tumor
      hyperthermia treatment with a 3-D anatomical human head model.
AB  - A re-entrant resonant cavity applicator system for non-invasive brain tumor
      hyperthermia treatments was presented. We have already confirmed the
      effectiveness of the heating properties of this heating system with cylindrical
      agar phantoms and with computer simulations.

PMID- 21096099
TI  - Theoretical simulation of the dual-heat-flux method in deep body temperature
      measurements.
AB  - Deep body temperature reveals individual physiological states, and is important
      in patient monitoring and chronobiological studies. An innovative dual-heat-flux
      method has been shown experimentally to be competitive with the conventional zero
      heat-flow method in its performance, in terms of measurement accuracy and step
      response to changes in the deep temperature. We have utilized a finite element
      method to model and simulate the dynamic process of a dual-heat-flux probe in
      deep body temperature measurements to validate the fundamental principles of the
      dual-heat-flux method theoretically, and to acquire a detailed quantitative
      description of the thermal profile of the dual-heat-flux probe. The simulation
      results show that the estimated deep body temperature is influenced by the
      ambient temperature (linearly, at a maximum rate of 0.03  degrees C/ degrees C)
      and the blood perfusion rate. The corresponding depth of the estimated
      temperature in the skin and subcutaneous tissue layer is consistent when using
      the dual-heat-flux probe. Insights in improving the performance of the dual-heat
      flux method were discussed for further studies of dual-heat-flux probes, taking
      into account structural and geometric considerations.

PMID- 21096100
TI  - Computation electrical variables induced by magnetic stimulation in 3D thigh
      model.
AB  - This paper presents the changes in the electrical variables induced in a 3D thigh
      model with femoral diaphyseal fracture when it is magnetically stimulated. Three
      cases with particular geometries of the models were considered: skin, muscle,
      cortical bone (CB), bone marrow, metal pin, and fracture shape. Fracture shape
      included electric properties for blood, cartilage, trabecular bone (TB), and
      cortical bone (CB), to represent the consolidation process. A Helmholtz coil was
      added to the thigh model as stimulation source. The stimulation signal was
      between 0.5 and 2 mT, and between 5 and 100 Hz. The results shown than induced
      electric signals were higher for a change in frequency than a change in magnetic
      field. An important dependence between frequency, magnetic field, fracture shape,
      and fracture properties was found. The result suggest that the consolidation
      process could be better if different magnetic stimulation levels were considered.

PMID- 21096101
TI  - Computational tool for modeling and simulation of mechanically ventilated
      patients.
AB  - The mechanical ventilator settings in patients with respiratory diseases like
      chronic obstructive pulmonary disease (COPD) during episodes of acute respiratory
      failure (ARF) is not a simple task that in most cases is successful based on the
      experience of physicians. This paper describes an interactive tool based in
      mathematical models, developed to make easier the study of the interaction
      between a mechanical ventilator and a patient. It describes all stages of system
      development, including simulated ventilatory modes, the pathologies of interest
      and interaction between the user and the system through a graphical interface
      developed in Matlab and Simulink. The developed computational tool allows the
      study of most widely used ventilatory modes and its advantages in the treatment
      of different kind of patients. The graphical interface displays all variables and
      parameters in the common way of last generation mechanical ventilators do and it
      is totally interactive, making possible its use by clinical personal, hiding the
      complexity of implemented mathematical models to the user. The evaluation in
      different clinical simulated scenes adjusts properly with recent findings in
      mechanical ventilation scientific literature.

PMID- 21096102
TI  - Respiratory impedance and corresponding phase-constancy in the 7.5 to 247.5 Hz
      frequency interval for healthy subjects.
AB  - This paper presents contributions on respiratory impedance and its phase
      constancy effects at high frequencies; i.e. 7.5-247.5 Hz. Measurements of 14
      healthy volunteers are used to provide the input impedance values. It is shown,
      via the modulus-phase characteristics, that the impedance poses a typical
      frequency-independent behavior, known as phase constancy. We propose an
      electrical ladder network analogue for which we identify a set of parameters from
      these real-life measurements. The results presented in this paper support earlier
      theoretical insights on the appearance of phase constancy in ladder networks and
      the estimated model parameters have meaningful values. The phase constancy
      implies that the respiratory system is fractal and that the tissue exhibits
      viscoelastic properties.

PMID- 21096103
TI  - An automated online positioning system and simulation environment for multi
      electrodes in extracellular recordings.
AB  - Extracellular recordings are a key tool to record the activity of neurons in
      vivo. Especially in the case of experiments with behaving animals, however, the
      tedious procedure of electrode placement can take a considerable amount of
      expensive and restricted experimental time. Furthermore, due to tissue drifts and
      other sources of variability in the recording setup, the position of the
      electrodes with respect to the recorded neurons can change causing low recording
      quality. The contributions of this work are threefold. We introduce a quality
      measure for the recording position of the electrode which should be maximized
      during recordings and is especially suitable for the use of multi-electrodes. An
      automated positioning system based on this quality measure is proposed. The
      system is able to find favorable recording positions and adapts the electrode
      position smoothly to changes of the neuron positions. Finally, we evaluate the
      system using a new simulator for extracellular recordings based on realistically
      reconstructed 3D neurons.

PMID- 21096104
TI  - Is pulse transit time a good indicator of blood pressure changes during short
      physical exercise in a young population?
AB  - The Pulse Transit Time (PTT) is generally assumed to be a good surrogate measure
      to comfortably track blood pressure (BP) and blood pressure changes. This paper
      investigates PTT variations for healthy young subjects during a sequence of short
      term physical exercises. PTT was measured by two different methodologies having
      different measurement accuracies as well as underlying assumptions: the total PTT
      from heart to fingertip and the difference of fingertip and earlobe PTTs. Small
      non consistent changes and very low correlation of both PTTs with systolic blood
      pressure (SBP) have been observed for the study population (-0.19 +/- 0.45 and
      0.22 +/- 0.46). In conclusion, there might be a need for an improved measurement
      accuracy of the sensors and data processing techniques in use. The applicability
      of the Moens-Korteweg equation is also questionable for young people having
      flexible arteries. In this case, significant radius changes do occur in the large
      arteries during exercise, which might counteract a PTT decrease with the BP
      elevation. These radius effects are excluded from the Moens-Korteweg model.

PMID- 21096105
TI  - Automatic wavelet detrending benefits to the analysis of cardiac signals acquired
      in a moving wheelchair.
AB  - Biomedical signals are customarily overlaid with interferences and noise,
      furthermore, baseline wandering is another significant drawback to their accurate
      interpretation, especially if the implementation platform is a wheelchair. The
      nonlinear processes which generate the physiologic signals, and the disturbances,
      regularly exclude, or limit, the usage of classical linear techniques, hence,
      among other options, wavelets have been used to decompose the signals.
      Unobtrusively acquired signals are prone to have important baseline fluctuations,
      namely contactless impedance plethysmogram, and ballistocardiogram, therefore
      making them apposite to detrending. Sensing hardware was embedded in a wheelchair
      to acquire these signals, given the valuable information provided about the
      cardiovascular system of the monitored subject. This work also reports the
      improvements achieved by automatic wavelet detrending application in the real
      time processing of these signals. Although significant baseline wavering is
      acquired, important enhancements are swiftly computed without noteworthy error.

PMID- 21096106
TI  - Comparison of systolic time interval measurement modalities for portable devices.
AB  - Systolic time intervals (STI) have shown significant diagnostic and prognostic
      value to assess the global cardiac function. Their value has been largely
      established in hospital settings. Currently, STI are considered a promising tool
      for long-term patient follow-up with chronic cardiovascular diseases. Several
      technologies exist that enable beat-by-beat assessment of STI in personal health
      application scenarios. A comparative study is presented using the
      echocardiographic gold standard synchronized with impedance cardiography (ICG),
      phonocardiography (PCG) and photoplethysmography (PPG). The ability of these
      competing technologies in assessing the pre ejection period (PEP) and the left
      ventricle ejection time (LVET) is given a general overview with comparative
      results.

PMID- 21096107
TI  - X-chromosome linked recessive diseases model.
AB  - We adopt the second Liapunov method to derive stability property of the
      equilibrium point in a non linear, discrete time, positive system, modeling the
      inheritance pattern of X-chromosome linked recessive diseases in the human
      population. By constructing a Liapunov function we derive globally asymptotically
      stable properties of the non trivial equilibrium point.

PMID- 21096108
TI  - Flexible modeling for anatomically-based cardiac conduction system construction.
AB  - We present a method to automatically deploy the peripheral section of the cardiac
      conduction system in ventricles. The method encodes anatomical information
      thorough rules that ensure that Purkinje network structures generated are
      realistic and comparable to those observed in ex-vivo studies. The core
      methodology is based in non-deterministic production rules that are parameterized
      by means of statistical functions. Input parameters allow the construction of a
      great diversity of Purkinje structures that could be incorporated in fine element
      ventricular models to perform electrophysiology simulations. Resulting Purkinje
      trees show good geometrical approximations of Purkinje core network and bundles
      when compared to histological diagrams and do not require user interaction.
      Simulations carried out with these models result in activation sequences
      remarkably similar to micro-electrode electrical mapping studies.

PMID- 21096109
TI  - Unraveling the conundrum of seemingly discordant protein-protein interaction
      datasets.
AB  - Most high-throughput experimental results of protein-protein interactions (PPIs)
      are seemingly inconsistent with each other. In this article, we re-evaluated
      these contradictions within the context of the underlying domain-domain
      interactions (DDIs) for two Escherichia coli and four Saccharomyces cerevisiae
      PPI datasets derived from high-throughput (yeast two-hybrid and tandem affinity
      purification) experimental platforms. For shared DDIs across pairs of compared
      datasets, we observed a remarkably high pair-wise correlation (Pearson
      correlation coefficient between 0.80 and 0.84) between datasets of the same
      organism derived from the same experimental platform. To a lesser degree, this
      concordance also held true for more general inter-platform and intra-species
      comparisons (Pearson correlation coefficient between 0.52 and 0.89). Thus,
      although varying experimental conditions can influence the ability of individual
      proteins to interact and, therefore, create apparent differences among PPIs, the
      physical nature of the underlying interactions, captured by DDIs, is the same and
      can be used to model and predict PPIs.

PMID- 21096110
TI  - Paired-pulse stimulation at glutamatergic synapses - pre- and postsynaptic
      components.
AB  - Paired-pulse stimulation is a standard protocol that has been used for decades to
      characterize dynamic systems: the differences in responses to two sequential
      identical stimuli as a function of inter-stimulus interval provide quantitative
      information on the dynamics of the system. In neuroscience, the paired-pulse
      protocol is also widely used at multiple levels of analysis, from behavioral
      conditioning to synaptic plasticity, and in particular to define the biomolecular
      mechanism of learning and memory. In a system as small and complex as synapses,
      it is extremely challenging - if not impossible - to experimentally gain access
      to the multitude of possible readouts. In the present study, we first introduce a
      computational synaptic modeling platform that we developed and calibrated based
      on experimental data from both our laboratories and a variety of publications. We
      then show how this platform allows not only to replicate experimental data, but
      also to go beyond technological boundaries and investigate the main parameters
      responsible for regulation of synaptic transmission and plasticity. The results
      provide critical information regarding the respective role of various subsynaptic
      processes and of their interactions. Additionally, this approach can strengthen
      our understanding of potential dysfunctions (pathologies) and suggest potential
      approaches to re-establish normal function.

PMID- 21096111
TI  - Predicting the target genes of intronic microRNAs using large-scale gene
      expression data.
AB  - Current microRNA target prediction techniques provide long lists of putative
      miRNA-target interactions, many of which are false positives. The goal of this
      paper is to identify functional targets in these lists based on biological
      evidence obtained from the expression profiles of the host genes of intronic
      miRNAs and those of their targets. We propose a scoring strategy for each
      interaction based on the combinatorial effect of miRNAs. In particular, the
      change in expression level of a target gene is expressed in terms of a linear
      combination of the host gene data which are used as surrogates for expression
      data of the intronic miRNAs. The parameters of this linear model give an estimate
      of the contribution of each intronic miRNA in down-regulating the target gene.
      The experimental results show that our prediction technique is able to detect
      several functional interactions. In addition, the analysis of mRNA microarrays
      after intronic miRNA transfection confirms that significantly down-regulated
      genes are among targets detected by our technique.

PMID- 21096112
TI  - Identification of gene regulatory networks from time course gene expression data.
AB  - Several methods have been proposed to infer gene regulatory networks from time
      course gene expression data. As the number of genes is much larger than the
      number of time points at which gene expression (mRNA concentration) is measured,
      most existing methods need some ad hoc assumptions to infer a unique gene
      regulatory network from time course gene expression data. It is well known that
      gene regulatory networks are sparse and stable. However, inferred network from
      most existing methods may not be stable. In this paper we propose a method to
      infer sparse and stable gene regulatory networks from time course gene expression
      data. Instead of ad hoc assumption, we formulate the inference of sparse and
      stable gene regulatory networks as constraint optimization problems, which can be
      easily solved. To investigate the performance of our proposed method,
      computational experiments are conducted on synthetic datasets.

PMID- 21096113
TI  - Inference of an in situ epidermal intracellular signaling cascade.
AB  - The stratified architecture of the epidermis makes it an ideal system in which to
      investigate intracellular signaling pathways within the context of a native
      tissue. We have applied quantitative imaging protocols to investigate the
      expression of 13 total-proteins and 4 phosphorylated-proteins across human
      epidermis. Plasma membrane, nuclear and/or cytoplasmic protein expression levels
      were measured along the gradient of keratinocyte differentiation. Dynamic
      Bayesian network techniques were used to infer conditional dependencies between
      the expression levels of target molecules and construct an associated cascade
      topology. The resulting networks were compared against a canonical network to
      investigate the extent to which known biochemical interactions could be
      recapitulated in situ. Biochemical evidence from the literature supported the
      majority (71-86%) of inferred network edges, however, overall coverage of the
      canonical network was relatively low (12-31%). Identified edges may represent key
      signaling pathway interactions which occur during keratinocyte differentiation.
      Inferred networks were ranked by model likelihood given the data and the top five
      were used to construct a consensus network. Several edges were present within
      this consensus network yet absent from the canonical network. These edges may
      represent putative interactions which occur in human epidermis.

PMID- 21096114
TI  - Graph theory-based measures as predictors of gene morbidity.
AB  - Previous studies have suggested that some graph properties of protein interaction
      networks might be related with gene morbidity. In particular, it has been
      suggested that when a polymorphism affects a gene, it is more likely to produce a
      disease if the node degree in the interaction network is higher than for other
      genes. However, these results do not take into account the possible bias
      introduced by the variance in the amount of information available for different
      genes. This work models the relationship between the morbidity associated with a
      gene and the degrees of the nodes in the protein interaction network controlling
      the amount of information available in the literature. A set of 7461 genes and
      3665 disease identifiers reported in the Online Mendelian Inheritance in Man
      (OMIM) was mined jointly with 9630 nodes and 38756 interactions of the Human
      Proteome Resource Database (HPRD). The information available from a gene was
      measured through PubMed mining. Results suggest that the correlation between the
      degree of a node in the protein interaction network and its morbidity is largely
      contributed by the information available from the gene. Even though the results
      suggest a positive correlation between the degree of a node and its morbidity
      while controlling the information factor, we believe this correlation has to be
      taken with caution for it can be affected by other factors not taken into account
      in this study.

PMID- 21096115
TI  - Extracting very simple diagnostic rules from microarray data.
AB  - We present an approach to deriving very simple classification rules from
      microarray data by first selecting very small gene subsets that can ensure highly
      accurate classification of cancers. Finding such minimum gene subsets can greatly
      reduce the computational load and "noise" arising from irrelevant genes. The
      derived simple classification rules allow for accurate diagnosis without the need
      for any classifiers. This work can simplify gene expression tests by including
      only a very small number of genes rather than thousands or tens of thousands of
      genes, which can significantly bring down the cost for cancer testing. These
      studies also call for further investigations into possible biological
      relationship between these small number of genes and cancer development and
      treatment. For example, we report the following simple, and yet 100% accurate,
      diagnostic rules involving only 2 genes to separate the 3 types of lymphoma
      patients: the patient has diffuse large B-cell lymphoma (DLBCL), if and only if
      the expression level of gene GENE1622X is greater than -0.75; the patient has
      chronic lymphocytic leukaemia (CLL), if and only if the expression level of gene
      GENE540X is less than -1; and the patient has follicular lymphoma (FL) otherwise,
      i.e., if and only if the expression level of gene GENE1622X is less than -0.75
      and the expression level of gene GENE540X is greater than -1.

PMID- 21096116
TI  - Platforms for controlled release of antibacterial agents facilitated by plasma
      polymerization.
AB  - Bacterial infections present an enormous problem causing human suffering and cost
      burdens to the healthcare systems worldwide. Herein we present several versatile
      strategies for controlled release of antibacterial agents which include silver
      ions as well as traditional antibiotics. At the heart of these release platforms
      is a thin film deposited by plasma polymerization. The use of plasma
      polymerization makes these strategies applicable to the surface of many types of
      medical devices since the technique for deposition of a polymer film from plasma
      in practically substrate independent.

PMID- 21096117
TI  - Fluorescence and diffuse reflectance spectroscopy for early cancer detection
      using a new strategy towards the development of a miniaturized system.
AB  - This paper describes the design of a miniature, cost-effective spectroscopy
      system for assessing tissue biochemical and morphological information using a few
      wavelengths. This instrument will integrate thin-film optical filters and silicon
      photodiodes, avoiding the use of a spectrograph and optical fibers. The
      components in the set-up design are described. The feasibility of using only 16
      wavelengths to accurately extract tissue properties is confirmed on physical
      tissue models. Also, the suitable spectral performance of several optical filters
      for the selection of these wavelengths is demonstrated. The reduced size of this
      device will make possible its implementation in an endoscopic capsule.

PMID- 21096119
TI  - Microwave tomographic imaging for osteoporosis screening: a pilot clinical study.
AB  - We are developing a microwave tomographic system for assessment of overall bone
      health. We hypothesize that as the mineralization of bone decreases due to the
      normal aging process and for more extreme situations such as osteoporosis, the
      dielectric property signature will also vary accordingly. To determine the merits
      of this approach, we have begun by performing initial exams of the heel to assess
      the level of image quality achievable. Early experience from our pilot study is
      encouraging and indicates that multiple planes of 2D images produce good
      representations of the 3D structural features within the heel.

PMID- 21096120
TI  - Proportional mechanical ventilation through PWM driven on/off solenoid valve.
AB  - Proportional strategies for artificial ventilation are the most recent form of
      synchronized partial ventilatory assistance and intra-breath control techniques
      available in clinical practice. Currently, the majority of commercial ventilators
      allowing proportional ventilation uses proportional valves to generate the flow
      rate pattern. This paper proposes on-off solenoid valves for proportional
      ventilation given their small size, low cost and short switching time, useful for
      supplying high frequency ventilation. A new system based on a novel fast
      switching driver circuit combined with on/off solenoid valve is developed. The
      average short response time typical of onoff solenoid valves was further reduced
      through the driving circuit for the implementation of PWM control. Experimental
      trials were conducted for identifying the dynamic response of the PWM driven
      on/off valve and for verifying its effectiveness in generating variable-shaped
      ventilatory flow rate patterns. The system was able to smoothly follow the
      reference flow rate patterns also changing in time intervals as short as 20 ms,
      achieving a flow rate resolution up to 1 L/min and repeatability in the order of
      0.5 L/min. Preliminary results showed the feasibility of developing a stand alone
      portable device able to generate both proportional and high frequency ventilation
      by only using on-off solenoid valves.

PMID- 21096118
TI  - A new drip infusion solution monitoring system with a free-flow detection
      function.
AB  - A new drip infusion solution monitoring system has been developed for hospital
      and care facility use. The system detects the fall of each drip chamber drop of
      fluid and also a free-flow situation. Three non-contacting copper foil electrodes
      are used. The electrodes are wrapped around the infusion supply polyvinyl
      chloride (PVC) tube from the solution bag, the drip chamber, and the infusion PVC
      tube from the drip chamber. Drip infusion fluids have electrical conductivity, so
      a capacitor is formed between the infusion fluid and each electrode. A thirty kHz
      sine wave is applied to the electrode wrapped around the infusion supply PVC tube
      from the solution bag. The capacity-coupled signal on the drip chamber electrode
      is the transducer output. When an infusion fluid drop is forming, its length and
      diameter, and therefore the drip chamber capacitance, are increasing, causing
      change in the output signal. The drip chamber electrode can detect the fall of
      each drip chamber drop of fluid. When the infusion solution becomes free-flow, an
      infusion fluid drop is not forming and the infusion fluid flows continuously.
      Therefore, the capacitance of the electrode around drip chamber does not change
      the output signal. On the other hand, the electrode wrapped around the infusion
      supply polyvinyl chloride tube under the drip chamber detects the thirty kHz sine
      wave conducted by the infusion fluid. The drip chamber electrodes and the
      infusion supply PVC tube under the drip chamber detect each drop of fluid and
      free-flow, respectively.

PMID- 21096121
TI  - A blood pressure monitor with robust noise reduction system under linear cuff
      inflation and deflation.
AB  - We have developed the non-invasive blood pressure monitor which can measure the
      blood pressure quickly and robustly. This monitor combines two measurement mode:
      the linear inflation and the linear deflation. On the inflation mode, we realized
      a faster measurement with rapid inflation rate. On the deflation mode, we
      realized a robust noise reduction. When there is neither noise nor arrhythmia,
      the inflation mode incorporated on this monitor provides precise, quick and
      comfortable measurement. Once the inflation mode fails to calculate appropriate
      blood pressure due to body movement or arrhythmia, then the monitor switches
      automatically to the deflation mode and measure blood pressure by using digital
      signal processing as wavelet analysis, filter bank, filter combined with FFT and
      Inverse FFT. The inflation mode succeeded 2440 measurements out of 3099
      measurements (79%) in an operating room and a rehabilitation room. The new
      designed blood pressure monitor provides the fastest measurement for patient with
      normal circulation and robust measurement for patients with body movement or
      severe arrhythmia. Also this fast measurement method provides comfortableness for
      patients.

PMID- 21096122
TI  - Design and analysis of an actuated endoscopic grasper for manipulation of large
      body organs.
AB  - During laparoscopic surgery, grasping of large body organs such as spleen,
      kidney, and liver, is a difficult task using conventional instruments. This paper
      describes the design and analysis of a novel actuated endoscopic grasper for
      manipulation of large internal organs. The designed instrument resembles a
      miniaturized three fingered hand with each finger consisting of two links. It
      could pass through a 10 mm trocar and then be opened inside the abdomen to grasp
      body organs up to 80 mm diameter. A detailed force analysis of the mechanism
      revealed that high actuating forces are required to grasp large organs. In order
      to facilitate the actuation of the grasper, its dimensions were optimized against
      the needed actuating force and an electro-mechanical actuator was designed to
      activate the system. Design optimization of the grasper resulted in up to 40%
      decrease in the required actuating force which could be effectively produced by a
      small linear actuator, with a moving course of 10 mm, placed inside the
      instrument handle. Finally, the efficacy of the actuated endoscopic grasper
      during a laparoscopic surgery operation was demonstrated using computer
      simulation.

PMID- 21096123
TI  - Comparison of manual steering and steering via joystick of a flexible rhino
      endoscope.
AB  - Flexible endoscopes are used in ENT surgery for examination tasks in cases
      wherever rigid endoscopes are unsuitable to reach certain positions in the nasal
      cavity. Until today they are steered by hand and no robotized system has been put
      into clinical practice. One qualification a robot manipulator system has to
      fulfill to be accepted is not to create new disadvantages compared to the
      conventional method in surgery. An important factor is the time needed to steer
      the new system compared to the time needed to steer the conventional system. In
      this article a robot manipulator system and an experiment are presented to
      compare the particular times test persons need to perform a certain task. This
      approach offers the possibility to benchmark the developed robot manipulator
      system and future systems for flexible rhino endoscopes.

PMID- 21096124
TI  - A design of RF stimulator which is similar to temperature distribution by
      moxibustion (preliminary study).
AB  - We developed a novel radio-frequency (RF) stimulator to mimic heat effects
      similar to the temperature distributions created by moxibustion in porcine
      tissue. Moxibustion is a traditional Oriental medicine technique using moxa,
      which is utilized not only to cure disease, but also to increase immunity.
      However, it may lead to undesired effects including severe pains, blisters, and
      burns because of the difficulty of controlling heat intensity during the process.
      To overcome these problems, a novel RF stimulator that can conduct thermal energy
      to the deep tissue of the body and also easily control the power of heat
      stimulation was proposed. RF stimulating protocols were designed to mimic the
      temperature profiles of two types of moxibustion. In our results, the temperature
      distributions created by the proposed protocols were similar to those attained by
      moxibustion. It was also shown that the proposed protocols were more effective
      than moxibustion for transferring heat effects into deep tissues.

PMID- 21096125
TI  - A fully automatic calibration framework for navigated ultrasound imaging.
AB  - Navigated ultrasound (US) imaging is used for the intra-operative acquisition of
      3D image data during image-guided surgery. The presented approach includes the
      design of a compact and easy to use US calibration device and its integration
      into a software application for navigated liver surgery. User interaction during
      the calibration process is minimized through automatic detection of the
      calibration process followed by automatic image segmentation, calculation of the
      calibration transform and validation of the obtained result. This leads to a
      fast, interaction-free and fully automatic calibration procedure enabling intra
      operative US calibration being performed by the surgical user.

PMID- 21096126
TI  - Design of a medical and laboratory equipment management program for the new
      standards certification achievement in Mexico.
AB  - Certification for healthcare institutions in Mexico is ruled by 2009 standards
      homologated with the Joint Commission International criteria. Nowadays,
      healthcare requires of medical equipment and devices, so it has become necessary
      to implement guidelines for its adequate management in order to reach the highest
      level of quality and safety at the lowest cost. The objective of this work was to
      develop a Medical and Laboratory Equipment Management Program, oriented to the
      improvement of quality, effectiveness and efficiency of the technological
      resources in order to meet the certification requirements. The result of this
      work allows to have an auto evaluation tool that focuses the efforts of the
      National Institute for Respiratory Diseases to the achievement of the new
      requirements established for the certification.

PMID- 21096127
TI  - Adaptive control of 2-wheeled balancing robot by cerebellar neuronal network
      model.
AB  - A new adaptive motor controller was constructed, and tested on the control of a 2
      wheeled balancing robot in simulation and real world. The controller consists of
      a feedback (PD) controller and a cerebellar neuronal network model. The structure
      of the cerebellar model was configured based upon known anatomical neuronal
      connection in the cerebellar cortex. Namely it consists of 120 granular (Gr)
      cells, 1 Golgi cell, 6 basket/stellate cells, and 1 Purkinje (Pk) cell. Each cell
      is described by a typical artificial neuron model that outputs a weighted sum of
      inputs after a sigmoidal nonlinear transformation. The 2 components of the
      proposed controller work in parallel, in a way that the cerebellar model
      adaptively modifies the synaptic weights between Gr and Pk as in the real
      cerebellum to minimize the output of the PD controller. We demonstrate that the
      proposed controller successfully controls a 2-wheeled balancing robot, and the
      cerebellar model rapidly takes over the PD controller in simulation. We also show
      that an abrupt load change on the robot, which the PD controller alone cannot
      compensate for, can be adaptively compensated by the cerebellar model. We further
      confirmed that the proposed controller can be applied to the control of the robot
      in real world.

PMID- 21096128
TI  - Simulation of a conductive shield plate for the focalization of transcranial
      magnetic stimulation in the rat.
AB  - Transcranial Magnetic Stimulation (TMS) in the rat is a powerful tool for
      investigating brain function. However, the state-of-the-art experiments are
      considerably limited because the stimulation usually affects undesired anatomical
      structures. A simulation of a conductive shield plate placed between the coil
      stimulator and the rat brain during TMS is presented. The Finite Element (FE)
      method is used to obtain the 3D electric field distribution on a four-layer rat
      head model. The simulations show that the shield plate with a circular window can
      improve the focalization of stimulation, as quantitatively seen by computing the
      three-dimensional half power region (HPR). Focalization with the shield plate
      showed a clear compromise with the attenuation of the induced field. The results
      suggest that the shield plate can work as a helpful tool for conducting TMS rat
      experiments on specific targets.

PMID- 21096129
TI  - Thermal heating of a retinal prosthesis: thermal model and in-vitro study.
AB  - In order to develop retinal implants with a large number of electrodes, it is
      necessary to ensure that they do not cause damage to the neural tissue by the
      heat that the electrical circuits generate. Knowledge about the threshold of the
      amount of power that induces thermal damage will greatly assist in development of
      power budgets for implants, which has a significant effect upon the design of
      implant circuitry. In this study, we developed and tested in-vitro equipment that
      can dissipate thermal energy in current prosthesis implantation sites while
      simultaneously measuring and recording temperature distributions at multiple
      locations along the retinal tissue. A finite element thermal model of the feline
      eye was also created and validated by the in-vitro tests allowing for a much
      larger spectrum of thermal influences to be evaluated without the additional cost
      of animal sacrifice.

PMID- 21096130
TI  - MR-compatible RF ablation system for online treatment monitoring using MR
      thermometry.
AB  - RF ablation (RFA) is used for thermal ablation of tumors in which the RF
      electrode is placed in the tissue under image-guidance. Because of the good tumor
      visibility and the lack of ionizing radiation, MR-guided RFA is the method of
      choice. Additionally, with the help of MR thermometry the RF ablation can be
      monitored during the intervention. Unfortunately, the imaging of an MR scanner is
      highly sensitive to interferences caused by external electrical signals. In this
      paper the high-power RF ablation signal of a commercially available medical
      therapy device is made MR-compatible. A design of a low-pass filter with high
      power compatibility is presented. The filter performance is demonstrated by means
      of simulations and measurements.

PMID- 21096132
TI  - Initial human feasibility study of DC ablation as a treatment for benign
      prostatic hyperplasia: 6 month follow-up data.
AB  - Direct current (DC) ablation is a novel non-thermal technology that causes
      focused coagulative necrosis in the lateral lobes of the prostate to treat benign
      prostatic hyperplasia (BPH). The necrosis is caused by a zone of non-physiologic
      pH which is created in a predictable pattern around each electrode in which a
      direct current is applied during treatment. The objective of this study was to
      optimize treatment parameters and assess treatment tolerability using
      transurethral DC ablation as an office-based treatment for BPH.

PMID- 21096131
TI  - Mathematical modeling of impedance controlled radiofrequency tumor ablation and
      ex-vivo validation.
AB  - Radiofrequency (RF) ablation uses RF current to heat and kill cancer applied via
      an electrode inserted under image-guidance, and is in clinical use for tumors in
      liver, lung kidney, and bone. Mathematical models are frequently used to
      determine tissue temperature during RF ablation, but most prior models do not
      include accurate implementation of power control algorithms as are used in
      clinical devices. We created a computer model employing the Finite Element
      Method, and implemented a clinically used impedance control algorithm. We assumed
      a rapid increase in tissue electrical conductivity upon vaporization to
      approximate tissue vapor formation and allow impedance control. We performed ex
      vivo tissue experiments where we measured the tissue temperature and impedance to
      validate the computer models. Impedance and temperature time course were
      comparable between model and experiments, and deviations are likely due to
      inaccurate data on temperature dependence of tissue properties. Ablation zone
      diameter was 33 mm in the computer model, and 29 +/- 3 mm in the experiments. Our
      computer model may more accurately allow tissue temperature calculation via
      including power control algorithms as used in clinical devices.

PMID- 21096133
TI  - Development of selective laser treatment techniques using mid-infrared tunable
      nanosecond pulsed laser.
AB  - Mid-infrared (MIR) laser with a specific wavelength can excite the corresponding
      biomolecular site to regulate chemical, thermal and mechanical interactions to
      biological molecules and tissues. In laser surgery and medicine, tunable MIR
      laser irradiation can realize the selective and less-invasive treatments and the
      special diagnosis by vibrational spectroscopic information. This paper showed a
      novel selective therapeutic technique for a laser angioplasty of atherosclerotic
      plaques and a laser dental surgery of a carious dentin using a MIR tunable
      nanosecond pulsed laser.

PMID- 21096134
TI  - The laser driven short-term heating balloon catheter: Relation between the
      chronic neointimal hyperplasia formation and thermal damage to arterial smooth
      muscle cells.
AB  - We proposed a novel laser-driven short-term heating angioplasty to realize
      restenosis-suppressive angioplasty for peripheral artery disease. In this study,
      we investigated the chronic intimal hyperplasia formation after the short-term
      heating dilatation in vivo, as well as the thermal damage calculation on arterial
      smooth muscle cells (SMCs). The prototype short-term heating balloon catheter
      with 5.0, 5.5, 6.0 mm phi in balloon diameter and 25 mm in balloon length were
      employed. The short-term heating dilatation was performed in porcine iliac
      arteries with dilatation conditions of 75 degrees C (N=4) and 65 degrees C (N=5)
      as peak balloon temperature, 18 +/- 4s as heating duration, 3.5 atm as balloon
      dilatation pressure. Four weeks after the balloon dilatation, the balloon-dilated
      artery segments were extracted and were stained with HE and picrosirius red for
      histological observation. In the case of 75 degrees C as the peak balloon
      temperature, neointimal hyperplasia formation was significantly reduced. In this
      case, the SMCs density in the artery media measured from the HE-stained specimen
      was 20% lower than that in the reference artery. According to the thermal damage
      calculation, it was estimated that the SMCs lethality in artery media after the
      short-term heating angioplasty was 20% in the case of 75 degrees C as the peak
      balloon temperature. We demonstrated that the short-term heating dilatation
      reduced the number of SMCs in artery media. We think this SMCs reduction might
      contribute to the suppression of chronic neointimal hyperplasia.

PMID- 21096135
TI  - Point process time-frequency analysis of respiratory sinus arrhythmia under
      altered respiration dynamics.
AB  - Respiratory sinus arrhythmia (RSA) is largely mediated by the autonomic nervous
      system through its modulating influence on the heartbeat. We propose an algorithm
      for quantifying instantaneous RSA as applied to heart beat interval and
      respiratory recordings under dynamic respiration conditions. The blood volume
      pressure derived heart beat series (pulse intervals, PI) are modeled as an
      inverse gaussian point process, with the instantaneous mean PI modeled as a
      bivariate regression incorporating both past PI and respiration values observed
      at the beats. A point process maximum likelihood algorithm is used to estimate
      the model parameters, and instantaneous RSA is estimated by a frequency domain
      transfer function approach. The model is statistically validated using Kolmogorov
      Smirnov (KS) goodness-of-fit analysis, as well as independence tests. The
      algorithm is applied to subjects engaged in meditative practice, with distinctive
      dynamics in the respiration patterns elicited as a result. Experimental results
      confirm the ability of the algorithm to track important changes in
      cardiorespiratory interactions elicited during meditation, otherwise not
      evidenced in control resting states.

PMID- 21096136
TI  - Time-varying analysis of autonomic control in response to spontaneous sighs in
      sickle cell anemia.
AB  - Sickle cell anemia (SCA) is a genetic disease which is characterized by painful
      episodes of vascular occlusions. In the present study, we investigated a
      potential contribution of the autonomic nervous system (ANS) in initiating such
      episodes. We observed prominent decreases in microvascular perfusion in response
      to spontaneous sighs, which may increase the likelihood of red blood cell
      polymerization followed by vascular occlusions in SCA patients. Time-varying
      spectral analysis of heart rate variability (HRV), based on recursive least
      squares estimation, was employed to study the modulation of the ANS in response
      to sighs. To improve robustness of the spectral estimation while retaining its
      ability to track rapid changes, we propose a time-varying parameter estimate
      variability reduction (TV-PEVR) technique. Because respiration patterns can vary
      considerably across subjects, we employed a time-varying autoregressive with
      exogenous input (TV-ARX) model to adjust for the effect of respiration patterns
      on the HRV indices. Results from 8 SCA subjects and 9 normal controls suggested
      that the cardiac ANS responses to sighs are not different between the two groups,
      after adjusting for the effect of post-sigh respiration. However, the peripheral
      sympathetic response in SCA appeared to be enhanced in this group relative to
      normals, and sighs may play a role in initiation of vaso-occlusive events in this
      group of patients.

PMID- 21096137
TI  - Slow neuronal oscillations in the resting brain vs task execution: A BSS
      investigation of EEG recordings.
AB  - Spontaneous very low frequency oscillations (< 0.5 Hz) occurring within widely
      distributed neuroanatomical systems have been increasingly analyzed in brain
      imaging studies. Whilst being more prominent in the resting brain, these slow
      waves also persist into task sessions and may potentially interfere with active
      goal-directed attention, leading to periodic lapses in attention during task
      execution. This work presents a new experimental framework and a multistage
      signal processing methodology - comprising blind source separation (BSS) coupled
      with a neural network feature extraction and classification method - developed
      for assessing variations in the slow wave characteristics in EEG data recorded
      during periods of quiet wakefulness (termed as "rest"), and during visual tasks
      of various difficulty levels. Core results demonstrate that the amplitude and
      phase of the brain sources in the slow wave band share essential similarities
      during rest and task conditions, but are distinct enough to be classified
      separately. These slow wave variations are also significantly correlated with the
      level of cognitive attention assessed by task performance measures (such as
      reaction times and error rates). Moreover, the power of the brain sources in the
      slow wave band is attenuated during task, and the level of attenuation drops as
      the task difficulty level is increased, whilst the slow wave phase undergoes a
      change in structure (measured through entropy). The methodology and findings
      presented here provide a new basis for assessing neural activity during various
      mental conditions.

PMID- 21096138
TI  - EEG-EMG coherence estimated using time-varying autoregressive models in movement
      activated myoclonus in patients with progressive myoclonic epilepsies.
AB  - We aimed this study at verifying the appropriateness of bivariate time-varying
      autoregressive models in detecting EEG-EMG relationships and identifying the
      characteristics of myoclonus-related EEG changes in patients with two forms of
      progressive myoclonus epilepsy (PME). Our results indicate that TVAR analysis was
      able to detect the presence of prominent peaks of EEG-EMG coherence between the
      EMG and contralateral frontocentral EEG derivation in all patients, revealing
      differences in time-frequency spectral profiles associated to the two different
      forms of PMEs, possibly correlated with the severity of myoclonus.

PMID- 21096139
TI  - The impact of expertise on brain computer interface based salient image
      retrieval.
AB  - Autonomous decision making modules in computer vision application allow
      recognition and classification of different objects, persons, and events in
      images and video sequences and also make it possible to classify different sensor
      readings (e.g. images) according to their scientific saliencies. In this paper,
      we propose a new approach to create the training set for these algorithms by
      retrieving salient images using electroencephalogram (EEG) and brain computer
      interface (BCI) and rapid image presentation. To this end, two groups of
      subjects, namely, expert and novice subjects were asked to participate in our
      experiments. We show that a relatively high retrieval accuracy can be achieved
      for most of the subjects. Furthermore, to assess the impact of expertise on the
      retrieval process, we study their EEG signals separately and show that there is a
      clear difference in their brainwaves while observing salient images.

PMID- 21096140
TI  - Application of multivariate empirical mode decomposition for seizure detection in
      EEG signals.
AB  - We present a method for the analysis of electroencephalogram (EEG) signals which
      has the potential to distinguish between ictal and seizure-free intracranial EEG
      recordings. This is achieved by analyzing common frequency components in
      multichannel EEG recordings, using the multivariate empirical mode decomposition
      (MEMD) algorithm. The mean frequency of the signal is calculated by applying the
      Hilbert-Huang transform on the resulting intrinsic mode functions (IMFs). It has
      been shown that the mean frequency estimates for the ictal and seizure-free EEG
      recordings are statistically different, and hence, can serve as a test statistic
      to distinguish between the two classes of signals. Simulation results on real
      world EEG signals support the analysis and demonstrate the potential of the
      proposed scheme.

PMID- 21096141
TI  - Shrinkage approach for EEG covariance matrix estimation.
AB  - We present a shrinkage estimator for the EEG spatial covariance matrix of the
      background activity. We show that such an estimator has some advantages over the
      maximum likelihood and sample covariance estimators when the number of available
      data to carry out the estimation is low. We find sufficient conditions for the
      consistency of the shrinkage estimators and results concerning their numerical
      stability. We compare several shrinkage schemes and show how to improve the
      estimator by incorporating known structure of the covariance matrix.

PMID- 21096142
TI  - An analysis of sequence alignment: heuristic algorithms.
AB  - Sequence alignment becomes challenging with an increase in size and number of
      sequences. Finding optimal or near optimal solutions for sequence alignment is
      one of the most important operations in bioinformatics. This study aims to survey
      heuristics applied for the sequence alignment problem summarized in a time line.

PMID- 21096143
TI  - Clustering-based spot segmentation of cDNA microarray images.
AB  - Microarrays are utilized as that they provide useful information about thousands
      of gene expressions simultaneously. In this study segmentation step of microarray
      image processing has been implemented. Clustering-based methods, fuzzy c-means
      and k-means, have been applied for the segmentation step that separates the spots
      from the background. The experiments show that fuzzy c-means have segmented spots
      of the microarray image more accurately than the k-means.

PMID- 21096144
TI  - A comparative study for characterisation and prediction of tissue-specific DNA
      methylation of CpG islands in chromosomes 6, 20 and 22.
AB  - Advanced technology has enabled identification of tissue-specific methylated CpG
      islands of different human tissues. As methylation of CpG islands is involved in
      various biological phenomena and function of the DNA methylation is linked to
      various human diseases such as cancer, analysis of the CpG islands has become
      important and useful in characterising and modelling biological phenomena and
      understanding mechanism of such diseases. However, analysis of the data
      associated with the CpG islands is a quite new and challenging subject in
      bioinformatics, systems biology and epigenetics.

PMID- 21096145
TI  - A signal processing-based bioinformatics approach to assessing drug resistance:
      human immunodeficiency virus as a case study.
AB  - Measuring drug resistance is one of the challenging and essential pharmaceutical
      activities. It is a laborious and costly laboratory-based experimentation.
      Various clinical and experimental analyses for measuring drug resistance have
      been carried out. Results have been obtained for different types of therapeutic
      agents as a consequence of changes in the amino acids compositions in the
      sequence (mutation) of the organisms involved. In the same manner, the positions
      of these amino acids alterations and the level of resistance (folds) have also
      been experimentally identified. For example, G36S and V38M mutation in the Human
      Immunodeficiency Virus (HIV) Transmembrane glycoprotein (gp41) has been found to
      cause 100-fold resistance. However, there does not seem to have bioinformatics
      method developed in which the amino acid information of the proteins involved in
      the studies were used to computationally assess the degree of drug resistance
      without involving laboratory-based experimental procedure. The post-genomic era
      has witnessed the relevance of Bioinformatics approaches in the analysis of huge
      biomedical data. One such approach is the analysis of protein residues using
      digital signal processing technique such as informational spectrum method (ISM).
      Therefore, we propose a new bioinformatics method that is capable of assessing
      drug resistance without the use of any laboratory-based experiments. This new
      method incorporates ISM, sequence information of the proteins and other relevant
      information. By using the ISM and EIIP amino acid scale, the technique was
      applied in three classes of anti-HIV/AIDS drugs as a case study. It is observed
      that the protein residues of the susceptible strains attained the maximal peak
      amplitude at the consensus frequency while the resistant strains maintained lower
      amplitudes. This result signifies lower contribution from the resistant strains
      due to the mutation. The findings are consistent with those of the experimental
      ones and therefore suggest that the approach taken can be used to help assess
      drug resistance without laboratory-based experimentation. It should also be noted
      that the method can be applied in other drug resistance studies where sequence
      information of proteins is available and help design a computer-aided drug
      resistance calculator.

PMID- 21096146
TI  - Denoising embolic Doppler ultrasound signals using Dual Tree Complex Discrete
      Wavelet Transform.
AB  - Early and accurate detection of asymptomatic emboli is important for monitoring
      of preventive therapy in stroke-prone patients. One of the problems in detection
      of emboli is the identification of an embolic signal caused by very small emboli.
      The amplitude of the embolic signal may be so small that advanced processing
      methods are required to distinguish these signals from Doppler signals arising
      from red blood cells. In this study instead of conventional discrete wavelet
      transform, the Dual Tree Complex Discrete Wavelet Transform was used for
      denoising embolic signals. Performances of both approaches were compared. Unlike
      the conventional discrete wavelet transform discrete complex wavelet transform is
      a shift invariant transform with limited redundancy. Results demonstrate that the
      Dual Tree Complex Discrete Wavelet Transform based denoising outperforms
      conventional discrete wavelet denoising. Approximately 8 dB improvement is
      obtained by using the Dual Tree Complex Discrete Wavelet Transform compared to
      the improvement provided by the conventional Discrete Wavelet Transform (less
      than 5 dB).

PMID- 21096147
TI  - Portable digital esophageal stethoscope system.
AB  - Heart sound occurs when the heart contracts and expands. It provides information
      on myocardial contractility and blood vessels, which is not obtainable from ECG.
      For this reason, stethoscopy of heart sound in anesthesiology is a very crucial
      means for acquiring cardiac information and preventing intraoperative medical
      accidents, and it requires a system for precise objective measurement and
      analysis of heart sound and murmur. Thus, this study purposed to develop portable
      digital esophageal stethoscope (PDES) that can objectify and quantify heart sound
      and murmur. In this study, we designed PDES for precise measurement and analysis
      of heart sound and murmur data. Heart sound information obtained by inserting the
      sensor of the PDES into the patient's esophagus can be transmitted to a terminal
      or a PC and displayed on the screen The amplitude and waveform of heart sound are
      displayed using self-developed software Heart Sound 1.0. The results of
      experiment with the developed PDES showed that data on the amplitude and waveform
      of heart sound and murmur were produced stably in real-time. In addition, when
      heart sound was heard using a headphone, the sound was clear without external
      murmur. The PDES developed in this study, which complements the disadvantages of
      traditional esophageal stethoscope while preserving its advantages, could not
      only examine heart sound and murmur using an esophageal catheter but also display
      the amplitude and waveform of heart sound and murmur and measure the patient's
      body temperature. Accordingly, the developed PDES is expected to be useful in the
      continuous stethoscopy of heart sound during operation and to contribute to
      research on heart sound by providing heart sound data.

PMID- 21096148
TI  - Regional electric field induced by electroconvulsive therapy: a finite element
      simulation study.
AB  - The goal of this study is to investigate the regional distribution of the
      electric field (E-field) strength induced by electroconvulsive therapy (ECT), and
      to contrast clinically relevant electrode configurations through finite element
      (FE) analysis. An FE human head model incorporating tissue heterogeneity and
      white matter anisotropy was generated based on structural magnetic resonance
      imaging (MRI) and diffusion tensor MRI (DT-MRI) data. We simulated the E-field
      spatial distributions of three standard ECT electrode placements [bilateral (BL),
      bifrontal (BF), and right unilateral (RUL)] and an investigational electrode
      configuration [focal electrically administered seizure therapy (FEAST)]. A
      quantitative comparison of the E-field strength was subsequently carried out in
      various brain regions of interests (ROIs) that have putative role in the
      therapeutic action and/or adverse side effects of ECT. This study illustrates how
      the realistic FE head model provides quantitative insight in the biophysics of
      ECT, which may shed light on the differential clinical outcomes seen with various
      forms of ECT, and may guide the development of novel stimulation paradigms with
      improved risk/benefit ratio.

PMID- 21096149
TI  - Electroconvulsive therapy in the presence of deep brain stimulation implants:
      electric field effects.
AB  - The safety of electroconvulsive therapy (ECT) in patients who have deep brain
      stimulation (DBS) implants represents a significant clinical issue. A major
      safety concern is the presence of burr holes and electrode anchoring devices in
      the skull, which may alter the induced electric field distribution in the brain.
      We simulated the electric field using finite-element method in a five-shell
      spherical head model. Three DBS electrode anchoring techniques were modeled,
      including ring/cap, microplate, and burr-hole cover. ECT was modeled with
      bilateral (BL), right unilateral (RUL), and bifrontal (BF) electrode placements
      and with clinically-used stimulus current amplitude. We compared electric field
      strength and focality among the DBS implantation techniques and ECT electrode
      configurations. The simulation results show an increase in the electric field
      strength in the brain due to conduction through the burr holes, especially when
      the burr holes are not fitted with nonconductive caps. For typical burr hole
      placement for subthalamic nucleus DBS, the effect on the electric field strength
      and focality is strongest for BF ECT, which runs contrary to the belief that more
      anterior ECT electrode placements are safer in patients with DBS implants.

PMID- 21096150
TI  - Reduced spatial focality of electrical field in tDCS with ring electrodes due to
      tissue anisotropy.
AB  - For effective stimulation with tDCS, spatial focality of induced electrical field
      (EF) is one of the important factors to be considered. Recently, there have been
      some studies to improve the spatial focality via different types of electrodes
      and their new configurations: some improvements using ring electrodes were
      reported over the conventional pad electrodes. However, most of these studies
      assumed isotropic conductivities in the head. In this work, we have investigated
      the effect of tissue anisotropy on the spatial focality of tDCS with the 4+1 ring
      electrode configuration via a 3-D high-resolution finite element (FE) head model
      with anisotropic conductivities in the skull and white matter. By examining the
      profiles of the induced EF from the head models with isotropic and anisotropic
      conductivities respectively, we found that the spatial focality of the induced EF
      significantly drops and get diffused due to tissue anisotropy. Our analysis
      suggests that it is critical to incorporate tissue anisotropy in the stimulation
      of the brain via tDCS.

PMID- 21096151
TI  - Micro vs macro electrode DBS stimulation: A dosimetric study.
AB  - Deep Brain Stimulation (DBS) is a clinically suitable technique for the treatment
      of the Parkinson's disease. Recently, also other neurological disorders such as
      Tourette syndrome, obsessive-compulsive disorder, epilepsy are being to be
      treated with DBS. However, the debate on its therapeutic mechanisms of action is
      still open. In order to a better understanding of such mechanisms, in this work
      the attention is focused on the DBS micro-stimulation. Indeed, a micro electrodes
      registration and stimulation is a fundamental step, during the surgical phase, to
      optimize the technique in terms of DBS lead positioning and DBS signal
      parameters. In this paper a dosimetric analysis with micro electrodes has been
      carried out, showing a more focused distribution of the electrical potential
      induced in the neuroanatomical tissues and changes of the excited/inhibited
      regions, respect to a macro electrodes stimulation.

PMID- 21096152
TI  - Steering deep brain stimulation fields using a high resolution electrode array.
AB  - Deep brain stimulation (DBS) therapy relies on electrical stimulation of neuronal
      elements in small brain targets. However, the lack of fine spatial control over
      field distributions in current systems implies that stimulation easily spreads
      into adjacent structures that may induce adverse side-effects. This study
      investigates DBS field steering using a novel DBS lead design carrying a high
      resolution electrode array. We apply computational models to simulate voltage
      distributions and DBS activation volumes in order to theoretically assess the
      potential of field steering in DBS. Our computational analysis demonstrates that
      the DBS-array is capable of accurately displacing activation volumes with sub
      millimeter precision. Our findings demonstrate that future systems for DBS
      therapy may provide for more accurate target coverage than currently available
      systems achieve.

PMID- 21096153
TI  - Measuring nightly activity, body weight and body weight change rate with a sensor
      equipped bed.
AB  - A bed was equipped with four force transducers so that the location of the Center
      Of Mass (COM) can be computed, when the bed contains a person. The computation of
      the COM and its alterations in combination with the sum of all measured forces
      allows to compute the person's position in bed, an activity level, the resulting
      body weight and the corresponding weight change rate over time (overnight and
      long-term) as well as simply to determine whether the person is in the bed or
      not. The results of several overnight measurement experiments show, that the
      person's position in the bed (central, left, right) can be correctly detected,
      the proposed activity level is a promising indicator for the sleep-activity and
      furthermore the initial body weight as well as the nightly weight change rate can
      be determined.

PMID- 21096154
TI  - Ambient assisted living: a methodological approach.
AB  - In this paper, the most important challenges and trends related to the
      application of Ambient Assisted Living (AAL) methods and techniques to the
      social/healthcare context are discussed. In order to find out technical solutions
      to these challenges, the main methodological issues concerning the design of open
      and distributed architectures are analyzed. The objective is to improve the
      efficiency/cost ratio in the provision of social and healthcare services to
      citizens with special needs, through the application of new paradigms in the
      context of AAL environments. Finally, some results and conclusions regarding the
      proposed open architecture are illustrated for the case of a distributed
      biomedical sensor network designed by the authors following this methodology.

PMID- 21096155
TI  - On search guide phrase compilation for recommending home medical products.
AB  - To help people find desired home medical products (HMPs), we developed an
      intelligent personal health record (iPHR) system that can automatically recommend
      HMPs based on users' health issues. Using nursing knowledge, we pre-compile a set
      of "search guide" phrases that provides semantic translation from words
      describing health issues to their underlying medical meanings. Then iPHR
      automatically generates queries from those phrases and uses them and a search
      engine to retrieve HMPs. To avoid missing relevant HMPs during retrieval, the
      compiled search guide phrases need to be comprehensive. Such compilation is a
      challenging task because nursing knowledge updates frequently and contains
      numerous details scattered in many sources. This paper presents a semi-automatic
      tool facilitating such compilation. Our idea is to formulate the phrase
      compilation task as a multi-label classification problem. For each newly obtained
      search guide phrase, we first use nursing knowledge and information retrieval
      techniques to identify a small set of potentially relevant classes with
      corresponding hints. Then a nurse makes the final decision on assigning this
      phrase to proper classes based on those hints. We demonstrate the effectiveness
      of our techniques by compiling search guide phrases from an occupational therapy
      textbook.

PMID- 21096156
TI  - Internal validation of a telemedical system for monitoring patients with chronic
      respiratory diseases.
AB  - One of the most promising and innovative developments in medicine are telemedical
      systems. The system PulmoTel 2010 and its internal validation are presented,
      focusing on the system architecture, hardware, software and communication
      solutions. PulmoTel 2010 consists of a distant server managing users and medical
      devices, as well as data transmission, processing, storage and presentation. The
      server cooperates with home units used by patients, capable of performing lung
      function tests. All the elements communicate via the Internet, however other
      media, as wire and mobile telephony, can be additionally applied in regions with
      a less developed infrastructure. Internal validation of the system was performed
      using data generated by application simulating features of a home unit. It
      demonstrated an appropriate operation of the overall system and fulfillment of
      the main objectives of the project.

PMID- 21096157
TI  - Vital signs remote monitoring through multipoint videoconferencing.
AB  - A system for remote monitoring of patients' vital signs using multipoint
      videoconferencing is proposed. A multiparametric module and a videoconference
      server were developed to set up a proof-of-concept where a text was streamed live
      as data was captured, while a third party monitored it.

PMID- 21096159
TI  - Physical modeling of low-frequency sound propagation through human thoracic
      tissue.
AB  - This work aims at modeling, in the presence of simplifying physical and
      geometrical assumptions, acoustic wave propagation through human thoracic tissue.
      Presented here are preliminary modeling results that are indicative of dominant
      lung resonances at specific frequencies. These resonant modes strongly impact
      pressure distribution in the tissue as well as the pressure and acceleration at
      the tissue-air interface. Under the modeling conditions, the effect of these lung
      resonant modes outweighs that of bones on acoustic waves at these frequencies.

PMID- 21096158
TI  - A multipoint videoconference-based telemedicine system for electrocardiogram
      monitoring.
AB  - In this work, a system to transfer electrocardiogram image signal through
      videoconference is described. The approach proposed was tested in order to
      evaluate its performance and the quality of the signal received back from the
      videoconference. The performance presented good results as the system react
      rapidly and no losses of data were observed.

PMID- 21096160
TI  - Wakefulness estimation only using ballistocardiogram: nonintrusive method for
      sleep monitoring.
AB  - To evaluate sleep quality or autonomic nervous system, many annoying electrodes
      have be attached to subjects' body. It can disturb comfortable sleep and,
      moreover, since it is very expensive experiment, continuous sleep monitoring is
      difficult. Since heart rate reflects the autonomic nervous system, it is highly
      synchronized with the sympathetic activation during transition from non-REM sleep
      to wakefulness. When the transition occurred the heart rate abruptly increased
      clearly distinguished with other changes. By using this physiology, we tried to
      classify the wakefulness during the whole night sleep. Our final goal is adopting
      this method to the continuous monitoring in our daily life. electrocardiogram
      (ECG) is not the suitable. Subjects have to attach the electrodes by themselves
      in their housing to obtain ECG. In that point of view, we used the
      ballistocardiogram (BCG) that is the representative method to obtain heart beat
      nonintrusively. For ten normal subjects, the wakefulness classifications by using
      the heart rate dynamics were executed. Nine subjects showed substantial agreement
      with the visually-scored method, polysomnography (PSG), and only one subject
      showed moderate agreement in Cohen's kappa value.

PMID- 21096161
TI  - Approximate entropy as a measure of the airflow pattern complexity in asthma.
AB  - The scientific and clinical value of a measure of complexity is potentially
      enormous because complexity appears to be lost in the presence of illness. The
      changes introduced by asthma in respiratory mechanics and control of breathing
      may result in modifications in the airflow pattern. These changes may be
      interesting clinically, since they can reduce the ability of the patient to
      perform daily life activities. In this paper, we examine the effect of elevated
      airway obstruction on the complexity of the airflow pattern of asthmatic patients
      using the approximate entropy method (ApEnQ). This study involved 5 healthy and
      asthmatics with normal spirometric exam (5), mild (5), moderate (6) and severe
      (5) airway obstruction. A significant (p<0.002) reduction in ApEnQ was observed
      in asthmatic patients. This reduction was significantly correlated with
      spirometric indices of airway obstruction (R=0.60; p<0.001). These results are in
      close agreement with pathophysiological fundamentals, and suggest that in
      asthmatic patients the airflow pattern becomes less complex, which may reduce the
      adaptability of the respiratory system to perform exercise associated with daily
      life activities. Furthermore, our findings also suggest that ApEnQ may help the
      clinical evaluation of asthmatic patients.

PMID- 21096162
TI  - Electrical circuit models of the human respiratory system reflect small airway
      impairment measured by impulse oscillation (IOS).
AB  - The use of the forced oscillatory input impedance parameter, frequency-dependence
      of Resistance (fdR), to assess small airway impairment (SAI) has not been widely
      accepted due to concern about the effects of "upper airway shunt" on
      oscillometric resistance and low frequency reactance. On the other hand, recent
      medical studies suggest that low frequency reactance is a very sensitive index of
      treatment intervention directed at small airways. The present study was
      undertaken to analyze and compare Impulse Oscillometry (IOS) resistance and
      reactance data with model-derived indices of small airway function from two
      models of the respiratory impedance, one with, and the other without an element
      for upper airway shunt capacitance. Fifty six patients with stable chronic
      obstructive lung disease of varying severity due to Cystic Fibrosis (CF) and 21
      patients with asthma were evaluated by IOS testing. IOS data were input into the
      augmented RIC (aRIC) model with an upper airway shunt capacitance, and the
      extended RIC (eRIC) model, without a shunt capacitance element. Model-derived
      indices were compared between the two models for CF patients separately from
      asthma patients. We conclude that IOS indices of SAI are modeled equally well
      with or without upper airway shunt capacitance, and do not seem to be dependent
      on upper airway shunt capacitance.

PMID- 21096163
TI  - One-dimensional computational model of pulse wave propagation in the human
      bronchial tree.
AB  - Airflow in the respiratory system has been predominantly studied in rigid ducts.
      Three-dimensional simulations are computationally expensive. One-dimensional (1
      D) modelling offers a good compromise between accuracy and computational cost. In
      this work we described the propagation of air pulse in a model of human airways
      using the 1-D equations of flow in compliant vessels. Seven generations of
      bifurcations, starting from the trachea, were studied. Peripheral airways (from
      the 8(th) to 23(rd) generation) were modelled using lumped parameter models.
      Peripheral resistance values for normal and emphysematous lungs were taken from
      the literature. An acceleration pulse, very short in time, was enforced at the
      inlet of trachea. The results suggest that compression (positive pressure peaks)
      and expansion (negative pressure peaks) waves are generated according to the
      reflection coefficients of the corresponding reflection sites (bifurcations and
      terminal reflections). Different values for peripheral bronchial resistance
      generate three different terminal reflections, all negative with different wave
      amplitudes. The sensitivity of the code to different peripheral resistances
      suggests that the 1-D formulation is a promising tool for a better understanding
      of the impact of disease on the velocity and pressure waveforms in the first
      generations of airway vessels.

PMID- 21096164
TI  - Mechanical analysis of an oscillatory positive expiratory pressure device used in
      respiratory rehabilitation.
AB  - This article aims to characterize the mechanical behavior of the Acapella Blue, a
      respiratory rehabilitation device designed to aid sputum clearance. In this
      scope, the present study initially describes in detail the peak-to-peak
      oscillation amplitude (App) and peak frequency (fp) behavior, as well as positive
      pressure level (Ppl), in the flow range more comonly found in practice. The
      parameters were evaluated in all 5 adjustment levels of the equipment in
      intervals of 50 mL/s. The device characterization has shown fp up to 23 Hz, App
      from 0.2 to 2.8 cmH(2)O and Ppl ranging from 1.2 to 13.5 cmH(2)O. The studied
      device may produce oscillation in the ranges of ciliary movements and respiratory
      system resonance frequency of patients with respiratory diseases. Data obtained
      in this work may help to optimize the use of the Acapella Blue device in
      respiratory rehabilitation. Suggestions for the practical use of the device are
      also presented.

PMID- 21096165
TI  - Evaluation of pulmonary rehabilitation after lung resection through opto
      electronic plethysmography.
AB  - The aim of this study is to evaluate the Pulmonary Rehabilitation (PR) and post
      operative complications on lung cancer patients by means of opto-electronic
      plethysmography (OEP). FEV1 and FVC have been measured through OEP on 13 lung
      cancer patients, before and after lobectomy and after pulmonary rehabilitation
      (PR). In every patient, FEV1 decreases after surgery, whereas FVC decreases only
      in 8 patients. Mean FEV1 and FVC decrease in every compartment of chest wall (CW)
      and in CW after lobectomy and improve in post-rehabilitation phase
      (DeltaFEV1(CW)=+31%; DeltaFVC(CW) = +13%). The highest positive variation of FEV1
      has been measured in rib-cage abdominal compartment (DeltaFEV1(RCa) =+59%) and of
      FVC in abdomen (DeltaFVC(AB) = +24%), after PR.

PMID- 21096166
TI  - Spectral analysis of the RR series and the respiratory flow signal on patients in
      weaning process.
AB  - A considerable number of patients in weaning process have problems to keep
      spontaneous breathing during the trial and after it. This study proposes to
      extract characteristic parameters of the RR series and respiratory flow signal
      according to the patients' condition in weaning test. Three groups of patients
      have been considered: 93 patients with successful trials (group S), 40 patients
      that failed to maintain spontaneous breathing (group F), and 21 patients who had
      successful weaning trials, but that had to be reintubated before 48 hours (group
      R). The characterization was performed using spectral analysis of the signals,
      through the power spectral density, cross power spectral density and Coherence
      method. The parameters were extracted on the three frequency bands (VLF, LF and
      HF), and the principal statistical differences between groups were obtained in
      bands of VLF and HF. The results show an accuracy of 76.9% in the classification
      of the groups S and F.

PMID- 21096167
TI  - Online estimation of respiratory mechanics in non-invasive pressure support
      ventilation: a bench model study.
AB  - An online algorithm for determining respiratory mechanics in patients using non
      invasive ventilation (NIV) in pressure support mode was developed and embedded in
      a ventilator system. Based on multiple linear regression (MLR) of respiratory
      data, the algorithm was tested on a patient bench model under conditions with and
      without leak and simulating a variety of mechanics. Bland-Altman analysis
      indicates reliable measures of compliance across the clinical range of interest
      (+/- 11-18% limits of agreement). Resistance measures showed large quantitative
      errors (30-50%), however, it was still possible to qualitatively distinguish
      between normal and obstructive resistances. This outcome provides clinically
      significant information for ventilator titration and patient management.

PMID- 21096168
TI  - Noninvasive measurement of inspiratory muscle performance by means of diaphragm
      muscle mechanomyographic signals in COPD patients during an incremental load
      respiratory test.
AB  - The study of mechanomyographic (MMG) signals of respiratory muscles is a
      promising noninvasive technique in order to evaluate the respiratory muscular
      effort and efficiency. In this work, the MMG signal of the diaphragm muscle it is
      evaluated in order to assess the respiratory muscular function in Chronic
      Obstructive Pulmonary Disease (COPD) patients. The MMG signals from left and
      right hemidiaphragm were acquired using two capacitive accelerometers placed on
      both left and right sides of the costal wall surface. The MMG signals and the
      inspiratory pressure signal were acquired while the COPD patients carried out an
      inspiratory load respiratory test. The population of study is composed of a group
      of 6 patients with severe COPD (FEV1>50% ref and DLCO < 50% ref). We have found
      high positive correlation coefficients between the maximum inspiratory pressure
      (IPmax) developed in a respiratory cycle and different amplitude parameters of
      both left and right MMG signals (RMS, left: 0.68 +/- 0.11 - right: 0.69 +/- 0.12;
      Renyi entropy, left: 0.73 +/- 0.10 - right: 0.77 +/- 0.08; Multistate Lempel-Ziv,
      left: 0.73 +/- 0.17 - right: 0.74 +/- 0.08), and negative correlation between the
      Pmax and the maximum frequency of the MMG signal spectrum (left: -0.39 +/- 0.19 -
      right: -0.65 +/- 0.09). Furthermore, we found that the slope of the evolution of
      the MMG amplitude parameters, as the load increases during the respiratory test,
      has positive correlation with the %FEV1/FVC pulmonary function test parameter of
      the six COPD patients analyzed (RMS, left: 0.38 - right: 0.41; Renyi entropy,
      left: 0.45 - right: 0.63; Multistate Lempel-Ziv, left: 0.39 - right: 0.64). These
      results suggest that the information provided by MMG signals could be used in
      order to evaluate the respiratory effort and the muscular efficiency in COPD
      patients.

PMID- 21096169
TI  - A wearable respiratory biofeedback system based on body sensor networks.
AB  - Technology advantages of body sensor networks (BSN) have shown great deal of
      promises in medical applications. In this paper we introduced a wearable device
      for biofeedback application based on the BSN platform we had developed. The
      biofeedback device we have developed includes the heart rate monitoring belt with
      conductive fabric and the biofeedback device with respiration belt. A wearable
      respiratory biofeedback system was preliminarily explored based on the BSN
      platform. In-situ experiments showed that the BSN platform and the biofeedback
      device worked as intended.

PMID- 21096171
TI  - Cerebral autoregulation in the vertebral and middle cerebral arteries during
      combine head upright tilt and lower body negative pressure in healthy humans.
AB  - The majority of cerebral autoregulation research has focused on the middle
      cerebral artery. However, many symptoms of presyncope indicate posterior cerebral
      hypoperfusion. To address this issue, we measured cerebrovascular reactivity,
      cerebral blood flow velocity and dynamic cerebral autoregulation in the middle
      cerebral artery and vertebral arteries during orthostatic stress to presyncope in
      9 healthy subjects. There was no significant difference in either the decline in
      cerebral blood flow velocity or indices of dynamic cerebral autoregulation
      between the middle cerebral and vertebral arteries prior to or during presyncope.
      In conclusion, there is no significant difference in regulation of blood flow
      between the vertebral artery and middle cerebral artery in healthy subjects.
      Further study is required to determine whether or not a difference exists in
      syncopal patient populations.

PMID- 21096170
TI  - Development of a cardiorespiratory monitoring system based on pressure change of
      aircushion.
AB  - Heartbeat and respiration are fundamental vital signs used for estimation of
      patient's status. In this study, we have proposed a simple method to monitor the
      heartbeat and respiration based on displacements of human body which occur due to
      periodic heartbeat and breathing.

PMID- 21096172
TI  - Fast tracking of a given heart rate profile in treadmill exercise.
AB  - This paper investigates the application of a multi-loop PID controller in an
      automated treadmill exercise machine. The approach is to design a computer
      controlled treadmill control system for the regulation of heart rate (HR) during
      treadmill exercise. A single-input and multiple-output (SIMO) controller was
      implemented to fast track a given heart rate profile in treadmill exercise. Two
      separate single-input and single-output (SISO) PID control systems are initially
      implemented to modify either the treadmill speed or its angle of inclination in
      order to achieve a desired HR. The purpose of this paper is to apply a SIMO
      control system by implementing a control algorithm which includes the two PID
      controllers working simultaneously to track the desired HR profile. The
      performance of the SIMO and SISO control systems are compared through the closed
      loop responses recorded during experimentation. This would also help future
      development of safe treadmill exercise system.

PMID- 21096173
TI  - Reproducibility of heart rate turbulence indexes in heart failure patients.
AB  - Cardiovascular oscillations following spontaneous ventricular premature complexes
      (VPC) are characterized by a short-term heart rate fluctuation known as heart
      rate turbulence (HRT) described by the so-called turbulence onset (TO) and slope
      (TS). Despite a recent written consensus on the standard of HRT measurement,
      reproducibility data are lacking. Aim of the paper was a reproducibility study of
      HRT indexes in heart failure patients (HF). Eleven HF patients underwent two 24h
      ECG Holter recordings, spaced 7 +/- 5 days. A paired t test was used to assess
      the clinical stability of patients during the study period and the number of PVC
      in Holter recordings' couples. Both TO and TS indexes were calculated for each
      isolated VPC, and due to their skewed distribution, reproducibility of median and
      mean TO and TS was studied by Bland-Altman technique. Results showed that median
      HRT indexes might be preferred to commonly suggested mean values and that,
      although TO showed lower bias value than TS, TS can be considered much more
      reproducible than TO, comparing limits of agreements with normal values. This
      preliminary results suggest the use of medians instead of mean HRT indexes values
      and a reliability of the turbulence slope greater than the turbulence onset
      index.

PMID- 21096174
TI  - A miniature on-chip multi-functional ECG signal processor with 30 uW ultra-low
      power consumption.
AB  - In this paper, a miniature low-power Electrocardiogram (ECG) signal processing
      application specific integrated circuit (ASIC) chip is proposed. This chip
      provides multiple critical functions for ECG analysis using a systematic wavelet
      transform algorithm and a novel SRAM-based ASIC architecture, while achieves low
      cost and high performance. Using 0.18 um CMOS technology and 1 V power supply,
      this ASIC chip consumes only 29 uW and occupies an area of 3 mm(2). This on-chip
      ECG processor is highly suitable for reliable real-time cardiac status monitoring
      applications.

PMID- 21096175
TI  - Derive right precordial leads at higher intercostal spaces from 12-lead system
      for diagnosis of Brugada syndrome.
AB  - Recording the right procordial leads at higher intercostal spaces (ICS) can raise
      the sensitivity of the diagnosis on Brugada syndrome using ECG. However, the
      directive measurement of the right precordial leads at the higher ICSs is tedious
      and impractical. In this paper, we proposed a derivation method based on the
      information redundancy in the 12-lead system to study the possibility of deriving
      the right precordial leads at the higher ICSs from the commonly used Mason-Likar
      12-lead ECGs. Through the evaluation based on the simulated Brugada-type ECGs and
      recorded ECGs from BS subjects, we found that the BS characteristic J wave and
      coved type ST elevation in the right precordial leads at the higher ICSs could be
      satisfyingly derived from the 12-lead ECGs. It is concluded that the derived
      precordial leads at the higher ICSs may serve as an assistant diagnosis tool to
      unmask Brugada syndrome.

PMID- 21096176
TI  - Modal analysis of ultrasound radiation force generated shear waves on arteries.
AB  - Arterial elasticity has gained importance in the past few decades as a predictor
      of cardiovascular diseases and mortality. Measuring the speed of propagation of
      the pressure wave traveling in the wall of the arteries has been used for a very
      long time to estimate the mechanical properties of the artery. Two of the major
      disadvantages of this method are the low temporal resolution (1 sample per
      second) and the low spatial resolution (carotid-femoral or carotid-radial
      segments). In our laboratory, we have been working on an ultrasound radiation
      force-based method to generate high frequency local shear waves, which will allow
      the study of the mechanical properties of short arterial segments within the
      heart cycle. In this work we present a modal analysis of the waves generated by
      our method on an excised pig artery. By doing a two-dimensional fast Fourier
      transform (2D FFT) of the propagating waves, it was possible to differentiate the
      multiple Lamb-like modes propagating in the wall. These modes showed changes with
      varying transmural pressure; this was expected as the arterial stiffness
      increases with pressure. This work shows the feasibility of our method for the
      study and characterization of propagating modes in the arterial wall. Future
      studies include developing a Lamb wave model for cylindrical viscoelastic
      structures to fit our data.

PMID- 21096177
TI  - Flow model with vessel tree for segmentation and registration with color Doppler
      ultrasound and CT.
AB  - Numerous phantoms for human organs are commercially available or designed for
      scientific purposes. None of these combine the imaging possibility with color
      Doppler ultra-sound (CDU) and computer tomography (CT) while providing vessel
      branches with bifurcations as natural landmarks.

PMID- 21096178
TI  - Spectral models for 1D blood flow simulations.
AB  - In this paper we introduce a new theoretical formulation for the description of
      the blood flow in the circulatory system. Starting from a linearized version of
      the Navier-Stokes equations, the Green's function of the propagation problem is
      computed in a rational form. As a consequence, the input-output transfer function
      relating the upstream and downstream pressure and blood flow is written in a
      rational form as well, leading to a time-domain state-space model suitable for
      transient analysis. The proposed theoretical formulation has been validated by
      pertinent numerical results.

PMID- 21096179
TI  - Evaluation of model-independent deconvolution techniques to estimate blood
      perfusion.
AB  - This report evaluates several methods to estimate blood perfusion and residue
      functions in dynamic contrast enhanced (DCE) MRI. Among these are model-dependent
      and model-independent techniques. All methods were applied to series of Monte
      Carlo simulations to evaluate the accuracy in order to reproduce different
      underlying vascular residue functions and blood perfusions. Of the model
      independent approaches the use of B-splines with Tikhonov regularization was
      shown to have a reasonable accuracy in blood perfusion estimations and was less
      biased than all model-dependent approaches. This technique seems most promising
      for application to experimental data.

PMID- 21096180
TI  - Automatic reconstruction of activation and velocity maps from electro-anatomic
      data by radial basis functions.
AB  - The integration of mapping techniques with suitable methods for the
      characterization and visualization of propagation patterns may enhance the
      targeting of critical arrhythmic areas, thus optimizing the ablative treatment of
      atrial arrhythmias. In this study, we tested the feasibility of an innovative
      approach for the automatic determination of activation and velocity maps from
      sparse data as provided by electro-anatomic mapping systems. The proposed
      algorithm reconstructed the activation process by a radial basis function (RBF)
      interpolation of mapping point latencies. Velocity vectors were analytically
      determined by differentiation of the interpolation function. The method was
      tested by a multistate cellular automaton simulation model, implemented on a
      CARTO-derived atrial endocardial surface, and reconstruction accuracy was
      evaluated as a function of the number of mapping points. The RBF algorithm
      accurately reconstructed wave propagation patterns in simulated tissues with
      homogeneous and heterogeneous conduction properties, consistently with the data
      access afforded by clinical practice. These preliminary results suggest the
      possible integration of the method with clinically-used mapping systems to favor
      the identification of specific propagation patterns and conduction disturbances.

PMID- 21096181
TI  - Dynamic modeling of the vascular system in the state-space.
AB  - Modern control theory allows the representation of cardiac dynamics in the state
      space, describing the operation of the vascular systems in terms of the
      cushioning effect of the arterial wall facing compliance changes. In this paper
      we use state equations to modeling the effect of the compliance variations on the
      arterial wall. The characteristics of the dynamics and of the calculated
      parameters of the model allow the distinction of hypertensive and normotensive
      subjects, in accordance to real clinical data.

PMID- 21096182
TI  - Numerical investigation of the hemodynamics in anatomically realistic lateral
      cerebral aneurysms.
AB  - Hemodynamically induced stress plays an important role in the progression and
      rupture of cerebral aneurysms. The current work describes computational fluid
      dynamics (CFD) simulations in anatomically realistic models of cerebral
      aneurysms. Twenty lateral aneurysms models were investigated. The models were
      obtained from three-dimensional rotational angiographic imaging data and CFD were
      studied under the same physiologically representative waveform of inflow. The
      flow was assumed to be laminar, non-Newtonian, and incompressible. The CFD models
      were solved with the finite elements package ADINA. Predictions of velocity field
      and wall shear stress (WSS) on the aneurysms were compared for the different
      cases. Linear correlations between the WSS on the aneurysm fundus at peak systole
      for lateral aneurysms with an area index were found.

PMID- 21096183
TI  - Comparison of steady-state and transient blood flow simulations of intracranial
      aneurysms.
AB  - Hemodynamics play an important role in the pathogenesis of intracranial aneurysms
      and patient-specific computational hemodynamic simulations could provide valuable
      information to clinicians. Transient simulations that capture the pulsatility of
      blood flow are commonly used for research purposes. However, steady-state
      simulations might provide enough information at a lower computational cost, which
      could help facilitate the introduction of hemodynamic simulations into clinical
      practice. In this study, we compared steady-state simulations to transient
      simulations for two aneurysms. The effect of a change in flow rate waveform was
      investigated and virtual treatment techniques were employed to compare post
      treatment flow reduction predictions. We found that the difference in the time
      averaged wall shear stress on the aneurysm was less than 5% and the distribution
      of wall shear stress was qualitatively assessed to be very similar.

PMID- 21096184
TI  - Computed wall stress may predict the growth of abdominal aortic aneurysm.
AB  - Growth rate of abdominal aortic aneurysm (AAA) is thought to be an important
      indicator of the potential risk of rupture. Wall stress is also thought to be a
      trigger for its rupture. However, stress change during the expansion of an AAA is
      unclear. Forty-four patients with AAAs were included in this longitudinal follow
      up study. They were assessed by serial abdominal ultrasonography and computerized
      tomography (CT) scans if a critical size was reached or a rapid expansion
      occurred. Patient-specific 3-dimensional AAA geometries were reconstructed from
      the follow-up CT images. Structural analysis was performed to calculate the wall
      stresses of the AAA models at both baseline and final visit. A non-linear large
      strain finite element method was used to compute the wall stress distribution.
      The average growth rate was 0.66 cm/year (range 0-1.32 cm/year). A significantly
      positive correlation between shoulder tress at baseline and growth rate was found
      (r=0.342; p=0.02). A higher shoulder stress is associated with a rapidly
      expanding AAA. Therefore, it may be useful for estimating the growth expansion of
      AAAs and further risk stratification of patients with AAAs.

PMID- 21096185
TI  - Changes in wall viscosity and filtering as determinant of carotid and femoral
      atherosclerotic plaque vulnerability: theoretical analysis.
AB  - Atherosclerotic plaque complication is a major cause of vascular accidents.
      Although a variety of factors have been proposed as key factors in these process,
      the mechanism that contribute to this problem remain to be characterized.
      Previously we demonstrated that changes in arterial wall viscous and elastic
      properties and/or in the filtering function (FF) could be part of the arterial
      wall alterations basis. If these properties are altered in arteries with
      atherosclerotic plaques remains to be analyzed. Our aims were 1) to analyze the
      arterial wall visco-elasticity and FF of carotid and femoral segments with
      atherosclerotic plaques, 2) to compare them with the mechanical behavior of
      segments without plaques (from the same artery) and of healthy arteries studied
      non-invasively. To this end, in each arterial segment, pressure and diameter
      signals were obtained, in vitro (circulation mock) and in vivo (non-invasive
      recordings). In atherosclerotic arteries recordings were performed on plaques and
      near regions without plaques. In each segment, the elasticity, the viscosity, and
      the wall FF were quantified. Atherosclerotic vessels, and particularly plaque
      regions, showed a reduced viscosity and FF. At the light of our results,
      hypothetical links between plaque events and changes in visco-elasticity and FF
      were discussed.

PMID- 21096186
TI  - Linear and nonlinear viscoelastic modeling of ovine aortic biomechanical
      properties under in vivo and ex vivo conditions.
AB  - This study uses linear and nonlinear viscoelastic models to describe the dynamic
      distention of the aorta induced by time-varying arterial blood pressure. We
      employ an inverse mathematical modeling approach on a four-parameter (linear)
      Kelvin viscoelastic model and two five-parameter nonlinear viscoelastic models
      (arctangent and sigmoid) to infer vascular biomechanical properties under in vivo
      and ex vivo experimental conditions in ten and eleven male Merino sheep,
      respectively. We used the Akaike Information Criterion (AIC) as a goodness-of-fit
      measure. Results show that under both experimental conditions, the nonlinear
      models generally outperform the linear Kelvin model, as judged by the AIC.
      Furthermore, the sigmoid nonlinear viscoelastic model consistently achieves the
      lowest AIC and also matches the zero-stress vessel radii measured ex vivo. Based
      on these observations, we conclude that the sigmoid nonlinear viscoelastic model
      best describes the biomechanical properties of ovine large arteries under both
      experimental conditions considered in this study.

PMID- 21096187
TI  - Distribution of active fiber stress at the beginning of ejection depends on left
      ventricular shape.
AB  - Left-ventricular shape is an important determinant of regional wall mechanics
      during passive filling. To examine the influence of left-ventricular shape for
      the ejection phase, the distribution of active fiber stress at the beginning of
      ejection was calculated in a finite element study. Hereto, finite element models
      were constructed with varying left-ventricular shapes, ranging from an elongated
      ellipsoid to a sphere, but keeping the initial cavity and wall volume constant. A
      realistic transmural gradient in fiber orientation was assumed. The passive
      myocardium was described by an incompressible hyperelastic material law with
      transverse isotropic symmetry along the muscle fiber directions. The activation
      of the left-ventricular wall was governed by the eikonal-diffusion equation.
      Active contraction was incorporated using a Hill-like model. For each left
      ventricular shape, a simulation was performed in which passive filling was
      followed by isovolumic contraction. It was found that the transmural gradient of
      active fiber stress at the beginning of ejection steepens at the mid-height level
      when the left ventricle becomes more spherical, which was also obtained
      previously for end-diastolic passive fiber stress and strain.

PMID- 21096188
TI  - 3D mesh based wall thickness measurement: identification of left ventricular
      hypertrophy phenotypes.
AB  - Left ventricular hypertrophy (LVH) is a complex cardiac condition mainly
      identified by the thickening of the myocardial wall. Although most of the
      contemporary cardiac imaging modalities provide high resolution 3D images, the
      wall thickness (WT) is still measured within the acquired planes. This way of
      measurement may introduce an error as cardiac wall is not necessarily orthogonal
      to the plane. In this study we analyze how different approaches to measure WT can
      affect an automatic identification of hypertrophy. The compared approaches are:
      WT measured along surface normal and the one provided by a medial surface. For
      both approaches we evaluated their ability to identify LVH phenotypes by testing
      with two classifiers: Transductive Confidence Machine-k Nearest Neighbor (TCM
      kNN) and Linear Discriminant Analysis (LDA). Fifty three subjects were included
      in this study: 18 patients with hypertrophic cardiomyopathy (HCM), 13 patients
      with hypertensive heart disease (HDD) and 22 sedentary subjects (CG). Medial
      surface based approach allowed obtaining higher classification accuracy in HDD
      patients, while normal based approach allowed for higher classification accuracy
      in HCM patients.

PMID- 21096189
TI  - Functional model of dual AV nodal pathway physiology.
AB  - Role of dual AV nodal pathway physiology in the atrioventricular nodal (AVN)
      conduction during atrial arrhythmias remains unclear. By using His electrogram
      alternans (HEA), we have developed a functional model of the atrioventricular
      conduction that incorporates the dual AV nodal pathway physiology. Experiments
      performed on 5 rabbit atrial-AVN preparations were used to develop and test the
      presented AV nodal functional model. HEAs from the inferior margin of the His
      bundle were used to identify fast and slow wavefront propagations (FP and SP).
      Conduction curves were calculated by using the model and compared with the real
      experiments, the root mean square error of the FP and SP were 7 +/- 4ms and 3 +/-
      3 ms respectively. In addition, the model has been used for illustrating the
      effects of the atrioventricular node modification, which has emerged as one of
      the alternatives for ventricular rate control during atrial fibrillation. The
      presented model can help in understanding some of the unclear AV node conduction
      mechanisms and should be considered as a step forward in understanding the AV
      node and specifically its dual pathway physiology.

PMID- 21096190
TI  - Spiral wave induced numerically using electrical stimulation and comparison with
      experimental results.
AB  - Experiments in vitro on a Microelectrode Array (MEA) platform show that
      electrical stimulation can provoke the generation of spiral waves in cardiac
      tissue. Nevertheless, the conditions leading to this artificial fibrillation
      state remain unclear. In order to have a better understanding of this phenomenon,
      a numerical simulation study has been conducted. The results obtained with a two
      dimensional FitzHugh-Nagumo model proved that it is possible to create spiral
      waves by adding a stimulation current under certain conditions, which are made
      explicit.

PMID- 21096191
TI  - Long-term biatrial recordings in post-operative atrial fibrillation.
AB  - Although atrial fibrillation (AF) is a common complication of cardiac surgery,
      its pathophysiology remains unclear. The study of post-operative AF demands for
      the recording of cardiac electrical activity in correspondence of AF onset and
      progression. Long-term recordings in post-surgery patients could provide this
      information, but, to date, have been limited to surface signals, which precludes
      a characterization of the arrhythmic triggers and substrate. In this study we
      demonstrate the feasibility of a continuous long-term recording of atrial
      electrical activities from the right and left atria in post-surgery patients.
      Local atrial epicardial electrograms are acquired by positioning temporary pacing
      wires in the right and left atria at the end of the intervention, while three day
      recordings are obtained by a digital holter recorder, adapted to epicardial
      signal features. The capability of the system to map local atrial activity and
      the possibility to obtain quantitative information on atrial rate and
      synchronization from the processed epicardial signals are proven in
      representative examples. The quantitative description of local atrial properties
      opens new perspective in the investigation of post-surgery AF.

PMID- 21096192
TI  - A novel biophysically-detailed mathematical model of rabbit Purkinje cell
      electrophysiology.
AB  - Purkinje fibres play an important role in cardiac conduction and have been
      implicated in arrhythmia in presence of diseased states, genetic mutations, or
      adverse side effects of drugs. For these reasons, the Purkinje assay is commonly
      used in pre-clinical in vitro drug assessment of arrhythmic risk. Several
      investigators have pointed out that rabbit Purkinje cells, compared to other
      species, have a better sensitivity in detecting arrhythmic risk.

PMID- 21096193
TI  - Exploring the parameter space of a rabbit ventricular action potential model to
      investigate the effect of variation on action potential and calcium transients.
AB  - Computational models for cardiomyocyte action potentials (AP) often make use of a
      large parameter set. This parameter set can contain some elements that are fitted
      to experimental data independently of any other element, some elements that are
      derived concurrently with other elements to match experimental data, and some
      elements that are derived purely from phenomenological fitting to produce the
      desired AP output. Furthermore, models can make use of several different data
      sets, not always derived for the same conditions or even the same species. It is
      consequently uncertain whether the parameter set for a given model is
      physiologically accurate. Furthermore, it is only recently that the possibility
      of degeneracy in parameter values in producing a given simulation output has
      started to be addressed. In this study, we examine the effects of varying two
      parameters (the L-type calcium current (I(CaL)) and the delayed rectifier
      potassium current (I(Ks))) in a computational model of a rabbit ventricular
      cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+))
      transient. It will subsequently be determined if there is degeneracy in this
      model to these parameter values, which will have important implications on the
      stability of these models to cell-to-cell parameter variation, and also whether
      the current methodology for generating parameter values is flawed. The accuracy
      of AP duration (APD) as an indicator of AP shape will also be assessed.

PMID- 21096194
TI  - Automatic code generation for solvers of cardiac cellular membrane dynamics in
      GPUs.
AB  - The modeling of the electrical activity of the heart is of great medical and
      scientific interest, as it provides a way to get a better understanding of the
      related biophysical phenomena, allows the development of new techniques for
      diagnoses and serves as a platform for drug tests. However, due to the multi
      scale nature of the underlying processes, the simulations of the cardiac
      bioelectric activity are still a computational challenge. In addition to that,
      the implementation of these computer models is a time consuming and error prone
      process. In this work we present a tool for prototyping ordinary differential
      equations (ODEs) in the area of cardiac modeling that aim to provide the
      automatic generation of high performance solvers tailored to the new hardware
      architecture of the graphic processing units (GPUs). The performance of these
      automatic solvers was evaluated using four different cardiac myocyte models. The
      GPU version of the solvers were between 75 and 290 times faster than the CPU
      versions.

PMID- 21096195
TI  - Real-time recognition of feedback error-related potentials during a time
      estimation task.
AB  - Feedback error-related potentials are a promising brain process in the field of
      rehabilitation since they are related to human learning. Due to the fact that
      many therapeutic strategies rely on the presentation of feedback stimuli,
      potentials generated by these stimuli could be used to ameliorate the patient's
      progress. In this paper we propose a method that can identify, in real-time,
      feedback evoked potentials in a time-estimation task. We have tested our system
      with five participants in two different days with a separation of three weeks
      between them, achieving a mean single-trial detection performance of 71.62% for
      real-time recognition, and 78.08% in offline classification. Additionally, an
      analysis of the stability of the signal between the two days is performed,
      suggesting that the feedback responses are stable enough to be used without the
      needing of training again the user.

PMID- 21096196
TI  - Parallel field programmable gate array particle filtering architecture for real
      time neural signal processing.
AB  - Both linear and nonlinear estimation algorithms have been successfully applied as
      neural decoding techniques in brain machine interfaces. Nonlinear approaches such
      as Bayesian auxiliary particle filters offer improved estimates over other
      methodologies seemingly at the expense of computational complexity. Real-time
      implementation of particle filtering algorithms for neural signal processing may
      become prohibitive when the number of neurons in the observed ensemble becomes
      large. By implementing a parallel hardware architecture, filter performance can
      be improved in terms of throughput over conventional sequential processing. Such
      an architecture is presented here and its FPGA resource utilization is reported.

PMID- 21096197
TI  - Application of system identification methods for decoding imagined single-joint
      movements in an individual with high tetraplegia.
AB  - This study investigated the decoding of imagined arm movements from M1 in an
      individual with high level tetraplegia. The participant was instructed to imagine
      herself performing a series of single-joint arm movements, aided by the visual
      cue of an animate character performing these movements. System identification was
      used offline to predict the trajectories of the imagined movements and compare
      these predictions to the trajectories of the actual movements. We report rates of
      25 - 50% for predicting completely imagined arm movements in the absence of a
      priori movements to aid in decoder building.

PMID- 21096198
TI  - Corticostriatal dynamics during learning and performance of a neuroprosthetic
      task.
AB  - Corticostriatal dynamics exhibit gross alterations over the course of natural
      motor learning, yet little is known about the role they play in neuroprosthetic
      tasks. We therefore investigated interactions between the striatum and primary
      motor cortex while rats learned to control a brain-machine interface. Striatal
      firing rates increased greatly from early to late in learning, suggesting that
      the striatum underlies similar functions in both natural and neuroprosthetic
      motor learning. In addition, spike-field coherence between neurons in primary
      motor cortex and local field potentials in the striatum increased greatly in the
      alpha band in late learning relative to early learning, suggesting the
      development of functional interactions in corticostriatal networks over the
      course of learning.

PMID- 21096199
TI  - A novel brain-computer interface based on the rapid serial visual presentation
      paradigm.
AB  - Most present-day visual brain computer interfaces (BCIs) suffer from the fact
      that they rely on eye movements, are slow-paced, or feature a small vocabulary.
      As a potential remedy, we explored a novel BCI paradigm consisting of a central
      rapid serial visual presentation (RSVP) of the stimuli. It has a large vocabulary
      and realizes a BCI system based on covert non-spatial selective visual attention.
      In an offline study, eight participants were presented sequences of rapid bursts
      of symbols. Two different speeds and two different color conditions were
      investigated. Robust early visual and P300 components were elicited time-locked
      to the presentation of the target. Offline classification revealed a mean
      accuracy of up to 90% for selecting the correct symbol out of 30 possibilities.
      The results suggest that RSVP-BCI is a promising new paradigm, also for patients
      with oculomotor impairments.

PMID- 21096200
TI  - Using ERPs for assessing the (sub) conscious perception of noise.
AB  - In this paper, we investigate the use of event-related potentials (ERPs) as a
      quantitative measure for quality assessment of disturbed audio signals. For this
      purpose, we ran an EEG study (N=11) using an oddball paradigm, during which
      subjects were presented with the phoneme /a/, superimposed with varying degrees
      of signal-correlated noise. Based on this data set, we address the question to
      which degree the degradation of the auditory stimuli is reflected on a neural
      level, even if the disturbance is below the threshold of conscious perception.
      For those stimuli that are consciously recognized as being disturbed, we suggest
      the use of the amplitude and latency of the P300 component for assessing the
      level of disturbance. For disturbed stimuli for which the noise is not perceived
      consciously, we show for two subjects that a classifier based on shrinkage LDA
      can be applied successfully to single out stimuli, for which the noise was
      presumably processed subconsciously.

PMID- 21096201
TI  - A pointwise correspondence based DT-MRI fiber similarity measure.
AB  - Diffusion Tensor Magnetic Resonance Imaging (DTI) fiber tractography is a way to
      reconstruct fiber tracts underlying data according to local anisotropic diffusion
      characteristics. Reliability of fiber tracts as a result of tractography
      decreases due to noise in the data, error accumulation during integration and
      stochastic nature of the underlying data. We proposed a new similarity measure
      based on point-wise correspondence between tracts. Laplacian Eigenmaps are used
      to embed the fiber tracts into R(3) based on the new similarity measure. We
      compared our method with a previously proposed method, on real and phantom data,
      that uses a 9D feature space to measure fiber similarity and showed that the new
      similarity measure results in a low dimensional manifold representing the fiber
      bundles. We presented preliminary results demonstrating that the fibers that fall
      far from this manifold correspond to outliers.

PMID- 21096202
TI  - Robust ODF smoothing for accurate estimation of fiber orientation.
AB  - Q-ball imaging was presented as a model free, linear and multimodal diffusion
      sensitive approach to reconstruct diffusion orientation distribution function
      (ODF) using diffusion weighted MRI data. The ODFs are widely used to estimate the
      fiber orientations. However, the smoothness constraint was proposed to achieve a
      balance between the angular resolution and noise stability for ODF constructs.
      Different regularization methods were proposed for this purpose. However, these
      methods are not robust and quite sensitive to the global regularization
      parameter. Although, numerical methods such as L-curve test are used to define a
      globally appropriate regularization parameter, it cannot serve as a universal
      value suitable for all regions of interest. This may result in over smoothing and
      potentially end up in neglecting an existing fiber population. In this paper, we
      propose to include an interpolation step prior to the spherical harmonic
      decomposition. This interpolation based approach is based on Delaunay
      triangulation provides a reliable, robust and accurate smoothing approach. This
      method is easy to implement and does not require other numerical methods to
      define the required parameters. Also, the fiber orientations estimated using this
      approach are more accurate compared to other common approaches.

PMID- 21096203
TI  - Maximum likelihood estimation for Rician distributed data in analytical q-ball
      imaging.
AB  - Analytical q-ball imaging is widely used for reconstruction of orientation
      distribution function (ODF) using diffusion weighted MRI data. Estimating the
      spherical harmonic coefficients is a critical step in this method. Least squares
      (LS) is widely used for this purpose assuming the noise to be additive Gaussian.
      However, Rician noise is considered as a more appropriate model to describe noise
      in MR signal. Therefore, the current estimation techniques are valid only for
      high SNRs with Gaussian distribution approximating the Rician distribution. The
      aim of this study is to present an estimation approach considering the actual
      distribution of the data to provide reliable results particularly for the case of
      low SNR values. Maximum likelihood (ML) is investigated as a more effective
      estimation method. However, no closed form estimator is presented as the
      estimator becomes nonlinear for the noise assumption of the Rician distribution.
      Consequently, the results of LS estimator is used as an initial guess and the
      more refined answer is achieved using iterative numerical methods. According to
      the results, the ODFs reconstructed from low SNR data are in close agreement with
      ODFs reconstructed from high SNRs when Rician distribution is considered. Also,
      the error between the estimated and actual fiber orientations was compared using
      ML and LS estimator. In low SNRs, ML estimator achieves less error compared to
      the LS estimator.

PMID- 21096204
TI  - Incorporating independent component analysis to Q-ball imaging for diffusion
      orientation distribution reconstruction.
AB  - In this paper, we investigate the incorporation of independent component analysis
      (ICA) with Q-ball imaging (QBI) to extract information on the diffusion
      orientation distribution function (ODF) from an inner voxel. In our approach, the
      ICA algorithm is applied to a mixture of ODFs which are constructed based on the
      analytical QBI solution. The numerical simulation results demonstrate that the
      proposed ICA framework can not only successfully separate the diffusion ODF from
      the noisy diffusion data, but also achieves better performance compared with a
      QBI solution when the data has a low signal to noise ratio (SNR).

PMID- 21096205
TI  - A new model for diffusion weighted MRI: complete Fourier direct MRI.
AB  - The diffusion weighted MR signal is modeled using particle methods. The model
      shows that the signal is the Fourier transform of the distribution function of
      the number of spins at the initial time at a given position with a given
      displacement integral value. The distribution function is computed via Fourier
      transform steps that keep the Hermitian property of the signal in order to
      guarantee that the distribution function is real valued. The function, which
      depicts the tissue microstructure 'as it is' without being tied to any
      expansions, transformations and assumptions such as Markovian property or
      symmetry about the spin motions, is displayed using isosurfaces overlayed on the
      spin density map for a fixed baboon brain sample.

PMID- 21096206
TI  - Use of Shannon information in treatment of high resolution diffusion MRI.
AB  - Diffusion MRI allows the obtaining of an approximation of the water
      displacement's probability density function (PDF) and orientation distribution
      function (ODF). Examples of techniques used in obtaining these distributions
      being q-space imaging (QSI), and q-ball imaging (QBI), respectively. Shannon
      information quantifies the discriminative power of a symbol based on its
      probability. We quantified the information amount of a white matter fiber bundle
      being used to discriminate those fibers using specific diffusion MRI data
      treatment techniques. The equations developed are new and it is also described
      how they will help in future experimental calculations. An example of
      experimental ODF surfaces and ODF based white matter fiber tracking in living
      humans is also shown to highlight possible future advantages of Shannon
      information usage in describing crossing white matter fiber bundles.

PMID- 21096207
TI  - An integrated, low noise patch-clamp amplifier for biological nanopore
      applications.
AB  - We present an integrated, low noise patch-clamp amplifier for biological nanopore
      applications. Our amplifier consists of an integrator-differentiator architecture
      coupled with a novel opamp design in the CMOS 0.35 um process. The post-layout
      full-chip simulation shows the input referred noise of the amplifier is 0.49 pA
      RMS over a 5 kHz bandwidth using a verified electrical model for the biological
      nanopore system. In our biological nanopore experiments studying protein-DNA
      interactions, we encounter capacitive transients with a nominal settling time of
      5 ms. Our amplifier design reduces the settling time to 0.2 ms, without requiring
      any compensation circuitry.

PMID- 21096208
TI  - Carbon nanotube electrodes for electrochemiluminescence biosensors.
AB  - The present application is based on the use of carbon nanotubes (CNTs) for
      biomolecular analysis using electrochemiluminescence (ECL) detection technique
      [1]-[9]. For this purpose we have grown self standing cylinder-shaped blocks of
      multi-wall CNTs (MWCNTs) by means of a catalytic chemical vapour deposition
      system, fed by camphor and ferrocene gases. The blocks were subsequently back
      contacted and encapsulated into epoxy resin as electrical insulator and sealant,
      for their use as voltammetric electrodes. A ruthenium-complex solution has been
      used as ECL label. It has been observed a periodical light emission that lasts
      for hundreds of cycles, likely due to the CNTs structure. Thanks to a data
      processing algorithm which exploits this behavior, the experiments show that it
      is possible to obtain a great increase in detection limit as compared to the
      common working metal electrodes (for example Au or Pt).

PMID- 21096209
TI  - A novel 16k micro-nail CMOS-chip for in-vitro single-cell recording, stimulation
      and impedance measurements.
AB  - In neurophysiological and pharmaceutical research, parallel and individual access
      to a dense population of in-vitro cultured neurons is a key feature for analyzing
      networks of neurons. This paper presents a 0.18um CMOS chip containing a dense
      array of micro-nail electrodes, a 128*128 sensor/actuator matrix with in-situ
      differential amplification circuits, pico-Ampere current stimulation, and
      impedance measurement circuits. Measurements on packaged chips show successful
      impedance measurements matching the simulation model and electrical recordings of
      in-vitro cultured cardiomyocytes, correlated with recorded changes in intra
      cellular calcium concentrations. This system is a first step towards a high
      throughput neuron/chip interface.

PMID- 21096210
TI  - Impedimetric biosignal analysis and quantification in a real-time biosensor
      system.
AB  - We describe our real-time, label-free, electrochemical impedance biosensor system
      with an emphasis on the use of an impedance response signal model to quantify
      assays. The signal processing for estimating model parameters from noisy data and
      the quantitative verification against target concentration and affinity are also
      presented.

PMID- 21096213
TI  - Ferrimagnetic nanoparticles enhance microwave heating for tumor hyperthermia
      therapy.
AB  - Localized tumor hyperthermia therapy has been intensively studied for the past
      three decades. One engineering limitation has been the difficulty of specifically
      targeting cancerous tissues in the normal tissue surroundings. Recent attention
      has turned to the deposition of nanoparticles in the tumor to enhance heating
      relative to its surroundings. The work in magnetic nanoparticles has focused on
      resonant hysteresis loop heating in the 100 to 300 kHz range, where that
      mechanism dominates - however extremely high magnetic field strengths are
      required to realize an advantage, up to 10(5) (A/m). We introduce experimental
      evidence that substantial advantages in heating can also be obtained at the
      microwave ISM frequency of 2.45 GHz when gamma-hematite (Fe(2)O(3)) is dispersed
      in media at concentrations on the order of 10(12) particles/mL.

PMID- 21096211
TI  - Towards a closed-loop system for stimulation and recording: an in vitro approach
      with embryonic cardiomyocytes.
AB  - Closed loop systems, in which stimulation parameters are adjusted according to
      recorded signals would reduce the occurrence of side effects of stimulation and
      broaden current therapeutic options. As a step towards a closed-loop clinical
      system, we developed a single electrode stimulation / recording system for an in
      vitro microelectrode array. The system was used in vitro to simultaneously
      stimulate and record cardiac cells. Results indicated that stimulation artifacts
      depend on the distance between recording electrode and stimulating electrode and
      on the voltage amplitude. No artifact reduction algorithm was required for
      detecting cardiac action potentials 2ms after stimulation if the stimulation
      pulses were less than or equal to +/- 1.5 V, and the distance from stimulation
      site was more than 200 um. Cardiac signal propagation was also investigated with
      this system.

PMID- 21096212
TI  - Photodynamic effects on basal cell carcinoma with topical Photosensitizer.
AB  - Photodynamic therapy (PDT) is a potential cancer therapy used in several clinical
      fields. Its application in dermatology following a fixed protocol usually
      generates good results. However, some cases of basal cell carcinoma show tumour
      persistence. The poor response observed in this type of pathology, whose lesions
      penetrate in the deeper layers of the skin, could be attributed to an
      insufficient accumulation of the PS (Photosensitizer) in deeper tissues. The
      development of accurate models could propose the adequate treatment dosimetry for
      those problematic cases in order to maximize the efficiency of the PDT treatment
      outcome. In this work we present a PDT model that tries to predict the
      photodynamic effect on the skin affected by a basal cell carcinoma with a
      topically administered photosensitizer. The results obtained allow us to know the
      evolution of the cytotoxic agent in order to estimate the necrotic area adjusting
      parameters such as the optical power, the photosensitizer concentration, the
      incubation and exposition time or the diffusivity and permeability of the damaged
      tissue.

PMID- 21096214
TI  - Practical evaluations on heating characteristics of thin microwave antenna for
      intracavitary thermal therapy.
AB  - Microwave thermal therapy is one of the modalities for cancer treatment. There
      are several schemes of microwave heating. The authors have been studying thin
      coaxial antenna for intracavitary microwave heating aiming at the treatment of
      bile duct carcinoma. Up to now, the heating characteristics of the antenna are
      investigated by numerical simulation and experiment for finding a possibility of
      the treatment. In this study, in order to consider practical situations of the
      treatment, heating characteristics of the antenna inserted into a metallic stent
      is evaluated by numerical simulations. Moreover, the relation between coagulation
      size of the tissue and the radiation power from the antenna is investigated
      experimentally. It must be considered, when the input power of the antenna is
      high (around several tens of watts). From these investigations, some useful
      results for practical treatments were found.

PMID- 21096215
TI  - Basic study of charring detection at the laser catheter-tip using back scattering
      light measurement during therapeutic laser irradiation in blood.
AB  - The purpose of this study is to investigate transient process of the charring at
      the laser catheter-tip in blood during therapeutic laser irradiation by the back
      scattering light measurement to detect precursor state of the charring. We took
      account of using photodynamic therapy for arrhythmia in blood through the laser
      catheter. We observed the influence of the red laser irradiation (lambda=663 nm)
      upon the shape of red blood cells (RBCs). The RBCs aggregation, round formation,
      and hemolysis were took place sequentially before charring. With a model blood
      sandwiched between glass plates simulated as a catheter-tip boundary, we measured
      diffuse-reflected-light power and transmitted-light power simultaneously and
      continuously by a microscopic optics during the laser irradiation. We found that
      measured light power changes were originated with RBCs shape change induced by
      temperature rise due to the laser irradiation. A gentle peak following a slow
      descending was observed in the diffuse-reflected-light power history. This
      history might indicate the precursor state of the charring, in which the
      hemolysis might be considered to advance rapidly. We think that the measurement
      of diffuse-reflected-light power history might be able to detect precursor state
      of charring at the catheter-tip in blood.

PMID- 21096216
TI  - Nonlinear dynamic analyses of single hippocampal neurons before and after long
      term potentiation.
AB  - Long-term potentiation (LTP) has long been considered an important phenomenon
      involved in learning and memory. However, the current literature lacks
      systematical analyses of single neuron dynamics before and after LTP induction.
      In this report, we applied an up to 3rd-order Volterra kernel to analyze the
      dynamics of single hippocampal neurons before and after LTP induction. Broadband
      Poisson random impulse trains with a 2 Hz mean frequency, which included
      physiologically plausible patterns, were applied to stimulate CA1 pyramidal
      neurons through Schaffer collateral before and after LTP induction. Corresponding
      somatic sub-threshold excitatory postsynaptic potentials (EPSPs) were recorded
      from CA1 neurons using whole-cell patch-clamp recording. The result suggests that
      LTP increases linear responses and depresses nonlinear responses. The phenomenon
      can be explained with both presynaptic and postsynaptic hypotheses. Further
      comparisons of voltage-clamp and current-clamp recordings are needed to
      distinguish the changes of dynamics in presynaptic and/or postsynaptic
      mechanisms.

PMID- 21096217
TI  - Surface EMG classification during dynamic contractions for multifunction
      transradial prostheses.
AB  - High usability myo-controlled devices require robust classification schemes
      during dynamic contractions. Therefore, this study investigates the impact of the
      training data set on the performance of several pattern recognition algorithms
      during dynamic contractions. It is shown that combined with a threshold to detect
      the onset of the contraction, current pattern recognition algorithms used on
      static conditions can maintain relatively high classification accuracy on dynamic
      situations. Moreover, the performance of the pattern recognition algorithms
      tested improved by optimizing the choice of the training set. Finally, the
      results also showed that rather simple approaches for classification of time
      domain features provide results comparable to more complex classification methods
      of wavelet features.

PMID- 21096218
TI  - Finding stationary brain sources in EEG data.
AB  - Neurophysiological measurements obtained from e.g. EEG or fMRI are inherently non
      stationary because the properties of the underlying brain processes vary over
      time. For example, in Brain-Computer-Interfacing (BCI), deteriorating performance
      (bitrate) is a common phenomenon since the parameters determined during the
      calibration phase can be suboptimal under the application regime, where the brain
      state is different, e.g. due to increased tiredness or changes in the
      experimental paradigm. We show that Stationary Subspace Analysis (SSA), a time
      series analysis method, can be used to identify the underlying stationary and non
      stationary brain sources from high-dimensional EEG measurements. Restricting the
      BCI to the stationary sources found by SSA can significantly increase the
      performance. Moreover, SSA yields topographic maps corresponding to stationary-
      and non-stationary brain sources which reveal their spatial characteristics.

PMID- 21096220
TI  - Neurophysiology of perceived confidence.
AB  - In a partial report paradigm, subjects observe during a brief presentation a
      cluttered field and after some time - typically ranging from 100 ms to a second -
      are asked to report a subset of the presented elements. A vast buffer of
      information is transiently available to be broadcasted which, if not retrieved in
      time, fades rapidly without reaching consciousness. An interesting feature of
      this experiment is that objective performance and subjective confidence is
      decoupled. This converts this paradigm in an ideal vehicle to understand the
      brain dynamics of the construction of confidence. Here we report a high-density
      EEG experiment in which we infer elements of the EEG response which are
      indicative of subjective confidence. We find that an early response during
      encoding partially correlates with perceived confidence. However, the bulk of the
      weight of subjective confidence is determined during a late, N400-like waveform,
      during the retrieval stage. This shows that we can find markers of access to
      internal, subjective states, that are uncoupled from objective response and
      stimulus properties of the task, and we propose that this can be used with
      decoding methods of EEG to infer subjective mental states.

PMID- 21096219
TI  - Simultaneous estimation of cortical activity during social interactions by using
      EEG hyperscannings.
AB  - In this paper we show how the possibility of recording simultaneously the
      cerebral neuroelectric activity in different subjects (EEG hyperscanning) during
      the execution of different tasks could return useful information about the
      "internal" cerebral state of the subjects. We present the results obtained by EEG
      hyperscannings during ecological task (such as the execution of a card game) as
      well as that obtained in a series of couples of subjects during the performance
      of the Prisoner's Dilemma Game. The simultaneous recordings of couples of
      interacting subjects allows to observe and to model directly the neural signature
      of human interactions in order to understand the cerebral processes generating
      and generated by social cooperation or competition. Results obtained in a study
      of different groups recorded during the card game revealed a larger activity in
      prefrontal and anterior cingulated cortex in different frequency bands for the
      player that leads the game when compared to other players. Results collected in a
      population of 10 subjects during the performance of the Prisoner's Dilemma
      suggested that the most consistently activated structure is the orbitofrontal
      region (roughly described by the Brodmann area 10) during the condition of
      competition in both the tasks. It could be speculated whether the pattern of
      cortical connectivity between different cortical areas in different subjects
      could be employed as a tool for assessing the outcome of the task in advance.

PMID- 21096221
TI  - Decoding state transitions in hippocampal oscillatory activity in mice.
AB  - Understanding the intricate dynamics of the hippocampal neural network, from
      which several types of neural oscillation rhythms arise, is an important step in
      uncovering the role of the hippocampus in the formation of memory. The different
      oscillation types commonly recorded in the hippocampus are thought to correspond
      to several states of neural network synchronization. Therefore, accurate
      segmentation and decoding of these underlying states provide useful insight on
      the rhythms' generation. In this study we use a framework based on Hidden Markov
      Models, coupled with a nonlinear dynamics method based on the Lempel-Ziv
      estimator. The method allows us to decode and model the neural state transitions.
      Network synchronization was induced by acute exposure to cholinergic agonist
      carbachol and oscillations were recorded from the Cornu Ammonis (CA1) region of
      the mouse hippocampus. Our results prove that deficits in cholinergic neuro
      transmission found in triple transgenic mice (3xTG, as Alzheimer's disease animal
      model) lead to increased instability in the hippocampal neural network
      synchronization.

PMID- 21096222
TI  - Application of frequency and sample entropy to discriminate long-term recordings
      of paroxysmal and persistent atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. At
      an early stage of the disease, AF may terminate spontaneously and is then
      referred to as paroxysmal AF. On the other hand, when external intervention is
      required for the arrhythmia to terminate, it is referred to as persistent AF. In
      this work, a method to discriminate between paroxysmal and persistent AF in the
      long-term ECGs is presented. The dominant frequency as well as the organization
      of the atrial activity are employed to characterize AF. The dominant atrial
      frequency (DAF) is estimated using hidden Markov model based frequency tracking,
      and organization is estimated by the sample entropy of the main atrial wave (MAW)
      and the first two harmonics, respectively. Long-term variations in DAF and
      organization from 50 ECG recordings were evaluated, showing that episodes of
      paroxysmal AF were consistently associated with lower DAF and organization of the
      MAW and the harmonics, than was persistent AF. Discrimination of paroxysmal and
      persistent AF resulted in classification rates of 84.1+/-26.1%, thus suggesting
      that it possible to discriminate between paroxysmal and persistent AF in patients
      without previously known AF history.

PMID- 21096223
TI  - A new method for automatic delineation of ECG fiducial points based on the Phasor
      Transform.
AB  - The present work introduces a new ECG delineator, based on the Phasor Transform,
      which is characterized by its robustness, low computational cost and mathematical
      simplicity. The method converts each instantaneous ECG sample into a phasor, thus
      being able to deal very precisely with P and T waves, which are of notably lower
      amplitude than the QRS complex. Initially, the method relies on the detection of
      R peaks and, next, onset and offset of the QRS complex are identified. Finally,
      taking the QRS as a reference, P and T waves are detected and delineated. The new
      delineator has been validated with the QT database, providing average values of
      sensitivity higher than 98.60% for the detection of all the significant ECG waves
      and fiducial points. Additionally, the average maximum time delineation error was
      lower than 6 ms and its standard deviation was in agreement with the accepted
      tolerances for expert physicians in the onset and offset identification for QRS,
      P and T waves. As a consequence, this new algorithm is able to achieve similar
      performance to the one provided by other well known delineation algorithms, but
      with notably lower computational cost.

PMID- 21096224
TI  - Application of empirical mode decomposition and Teager energy operator to EEG
      signals for mental task classification.
AB  - This paper presents a novel method for mental task classification from EEG
      signals using Empirical Mode Decomposition and Teager energy operator techniques
      on EEG data. The efficacy of these techniques for non-stationary and non-linear
      data has already been demonstrated, which therefore lend themselves well to EEG
      signals, which are also non-stationary and non-linear in nature. The method
      described in this paper decomposed the EEG signals (6 EEG signals per task per
      subject, for a total of 5 tasks over multiple trials) into their constituent
      oscillatory modes, called intrinsic mode functions, and separated out the trend
      from the signal. Teager energy operator was used to calculate the average energy
      of both the detrended signal and the trend. The average energy was used to
      construct separate feature vectors with a small number of parameters for the
      detrended signal and the trend. Based on these parameters, one-versus-one
      classification of mental tasks was performed using Linear Discriminant Analysis.
      Using both feature vectors, an average correct classification rate of more than
      85% was achieved, demonstrating the effectiveness of the method used.
      Furthermore, this method used all the intrinsic mode functions, as opposed to
      similar studies, demonstrating that the trend of the EEG signal also contains
      important discriminatory information.

PMID- 21096225
TI  - Measurement of distal EMG signals using a wearable device for reading facial
      expressions.
AB  - In this paper we present a quantitative analysis of electrode positions on the
      side of the face for facial expression recognition using facial bioelectrical
      signals. We show that distal electrode locations on areas of low facial mobility
      have a strong amplitude and are correlated to signals captured in the traditional
      positions on top of the facial muscles. We report on electrode position choice as
      well successful facial expression identification using computational methods. We
      also propose a wearable interface device that can detect facial bioelectrical
      signals distally in a continuous manner while being unobtrusive to the user. The
      proposed device can be worn on the side of the face and capture signals that are
      considered to be a mixture of facial electromyographic signals and other
      bioelectrical signals. Finally we show the design of an interface that can be
      comfortably worn by the user and makes facial expression recognition possible.

PMID- 21096226
TI  - Reducing electrocardiographic artifacts from electromyogram signals with
      independent component analysis.
AB  - The aim of this work was to reduce ECG artifacts from surface electromyogram
      (EMG) signals collected from lumbar muscles with the blind source separation
      technique based on independent component analysis (ICA). Using four EMG signals
      collected above erector spinal lumbar muscles from 27 subjects, the proposed
      method fail in separating the sources. However, when considering a single channel
      of EMG and the same one time-shifted by one sample, the FastICA allowed reducing
      the signal to ECG noise ratio.

PMID- 21096227
TI  - Merging PK/PD information in a minimally parameterized model of the neuromuscular
      blockade.
AB  - A recursive system identification algorithm that merges PK/PD information in a
      minimally parameterized Wiener model for the NMB level is presented. The results
      show that the coupling between one parameter from the linear block and one from
      the static nonlinearity is advantageous, when evaluated on a database of 60 real
      collected NMB cases.

PMID- 21096228
TI  - Tracking whole hand kinematics using extended Kalman filter.
AB  - This paper describes the general procedure, model construction, and experimental
      results of tracking whole hand kinematics using extended Kalman filter (EKF)
      based on data recorded from active surface markers. We used a hand model with 29
      degrees of freedom that consists of hand global posture, wrist, and digits. The
      marker protocol had 4 markers on the distal forearm and 20 markers on the dorsal
      surface of the joints of the digits. To reduce computational load, we divided the
      state space into four sub-spaces, each of which were estimated with an EKF in a
      specific order. We tested our framework and found reasonably accurate results (2
      4 mm tip position error) when sampling tip to tip pinch at 120 Hz.

PMID- 21096229
TI  - Surface electromyogram signals classification based on bispectrum.
AB  - This paper bispectrum is used to classify human arm movements and control a
      robotic arm based on upper limb's surface electromyogram signals (sEMG). We use
      bispectrum based on third-order cumulant to parameterize sEMG signals and
      classify elbow flexion and extension, forearm pronation and supination, and rest
      states by an artificial neural network (ANN). Finally, a robotic manipulator is
      controlled based on classification and parameters extracted from the signals. All
      this process is made in real-time using QNX (r) operative system.

PMID- 21096230
TI  - Fractal feature of sEMG from Flexor digitorum superficialis muscle correlated
      with levels of contraction during low-level finger flexions.
AB  - This research paper reports an experimental study on identification of the
      changes in fractal properties of surface Electromyogram (sEMG) with the changes
      in the force levels during low-level finger flexions. In the previous study, the
      authors have identified a novel fractal feature, Maximum fractal length (MFL) as
      a measure of strength of low-level contractions and has used this feature to
      identify various wrist and finger movements. This study has tested the
      relationship between the MFL and force of contraction. The results suggest that
      changes in MFL is correlated with the changes in contraction levels (20%, 50% and
      80% maximum voluntary contraction (MVC)) during low-level muscle activation such
      as finger flexions. From the statistical analysis and by visualisation using box
      plot, it is observed that MFL (p ~ 0.001) is a more correlated to force of
      contraction compared to RMS (p~0.05), even when the muscle contraction is less
      than 50% MVC during low-level finger flexions. This work has established that
      this fractal feature will be useful in providing information about changes in
      levels of force during low-level finger movements for prosthetic control or human
      computer interface.

PMID- 21096231
TI  - Decrement of uterine myometrial burst duration as a correlate to active labor: a
      Hilbert phase approach.
AB  - We propose a novel approach based on Hilbert phase to identify the burst in the
      uterine myometrial activity. We apply this approach to 24 serial
      magnetomyographic signals recorded from four pregnant women using a 151 SQUID
      array system. The bursts identified with this approach are evaluated for duration
      and are correlated with the gestational age. In all four subjects, we find a
      decrease in the duration of burst as the subject approaches active labor. As was
      shown in animal studies, this result indicates a faster conduction time between
      the muscle cells which activate a larger number of muscle units in a synchronous
      manner.

PMID- 21096232
TI  - Fourier and wavelet spectral analysis of EMG signals in maximal constant load
      dynamic exercise.
AB  - Frequency domain analyses of changes in electromyographic (EMG) signals over time
      are frequently used to assess muscle fatigue. Fourier based approaches are
      typically used in these analyses, yet Fourier analysis assumes signal
      stationarity, which is unlikely during dynamic contractions. Wavelet based
      methods of signal analysis do not assume stationarity and may be more appropriate
      for joint time-frequency domain analysis. The purpose of this study was to
      compare Short-Time Fourier Transform (STFT) and Continuous Wavelet Transform
      (CWT) in assessing muscle fatigue in maximal constant load dynamic exercise (100%
      W(max)). The results of this study indicate that CWT and STFT analyses give
      similar fatigue estimates (slope of median frequency) in maximal constant load
      dynamic exercise (P>0.05). However, the results of the variance was significantly
      lower for at least one of the muscles studied in CWT compared to STFT (P<0.05)
      indicating more variability in the EMG signal analysis using STFT. Thus, the
      stationarity assumption may not be the sole factor responsible for affecting the
      Fourier based estimates.

PMID- 21096233
TI  - Evaluation of a game controller using human stiffness estimated from
      electromyogram.
AB  - A motion controller which has an acceleration sensor increases reality and
      intuitiveness in sports games. But we adjust not only visible posture but also
      invisible force like stiffness and viscosity when we play sports. We propose a
      game controller using player's movement and force by using acceleration and
      electromyogram(EMG). In this research, we compared conventional motion controller
      and proposed method by using a golf game. The score was the distance between cup
      position and carried ball position. For beginner of video games, proposed method
      is superior than conventional. For well-trained video game players conventional
      button type controller wins on accurate input. Because it was difficult to keep
      arm stiffness constant than button. Using coarsely-quantized EMG might resolve
      this problem, then achieve intuitive and easy-to-use game controller.

PMID- 21096234
TI  - Wavelet analysis for Support Vector Machine classification of motor unit action
      potentials.
AB  - The paper presents a new method for neuromuscular disorders diagnosis based on
      analysis of scalograms determined by the Symlet 4 wavelets technique. Obtained
      results served for extraction of five features, which, after SVM analysis, were
      reduced to a single decision parameter allowing assigning the investigated cases
      to one of three groups: myogenic, neurogenic or normal. Software implementation
      of the method permitted to create a diagnostic tool for EMG investigation aid.
      The method characterizes high probability of accurate diagnosis of a muscle state
      with total error of 0.5% - 4 misclassifications out of 780 examined cases.

PMID- 21096235
TI  - Spike detection in extracellular recordings by hybrid blind beamforming.
AB  - In the case of extracellular recordings, spike detection algorithms are necessary
      in order to retrieve information about neuronal activity form the data. We
      present a new spike detection algorithm which is based on methods from the field
      of blind equalization and beamforming. In contrast to existing approaches, our
      method estimates several waveforms directly from the data and corresponding
      linear filters are constructed. The estimation is done in an unsupervised manner,
      and the few parameters of the algorithm are intuitive to set. The algorithm
      allows for superior detection performance, even when multiple neurons with
      various waveforms are present in the data. We compare our method with current
      state-of-the-art spike detection algorithms, and show that the proposed method
      achieves favorable results.

PMID- 21096236
TI  - Improving the classification rate of labor vs. normal pregnancy contractions by
      using EHG multichannel recordings.
AB  - Most of the studies on the synchronization between EHG signals, recorded during
      the same contractions at different locations, are limited to the use of only two
      channels. Multichannel techniques have however been widely applied to EEG signals
      but rarely to EHG. In this paper, we investigate the use of multichannel uterine
      EMG signals for classifying contractions. We compare the performance of phase
      synchronization in distinguishing between labor and normal pregnancy contractions
      by using either only two channels or a 4x4 matrix positioned on the woman's
      abdomen. We used two indexes to measure the phase synchronization: mean phase
      coherence and phase entropy. ROC curves indicate that the use of multichannel
      signals can significantly improve the classification rate of pregnancy and labor
      contractions.

PMID- 21096237
TI  - Partial Directed Coherence estimated on Stereo-EEG signals in patients with
      Taylor's type focal cortical dysplasia.
AB  - The study was aimed at evaluating the changes in dynamical connectivity, between
      interictal, preictal and ictal condition, among signals derived from StereoEEG
      recordings in patients with Taylor's type focal cortical dysplasia (FCD type-II),
      by means of Partial Directed Coherence and indexes derived from graph theory.
      Results showed that seizures are characterized by an increased synchronization,
      mainly within the regions involved in the generation of the epileptogenic
      activity. Our findings reveal that the proposed procedure can be considered a
      suitable techinque to properly identify the pathological synchronization
      mechanisms underlying seizure generation and to support the identification of the
      epileptogenic zone.

PMID- 21096238
TI  - A Yarbus-style experiment to determine auditory attention.
AB  - This paper presents an analysis of the merits of the original Yarbus experiment
      on eye movements with respect to judgments on differences in cognitive layer
      processes. The principles thus derived are applied to the development of an
      equivalent auditory experiment where, instead of eye movements, the response of
      the subject is observed by EEG measurements. Results from a preliminary trial are
      also included in which EEG analysis is used to ascertain the attended sound
      source in a multiple sound source environment. The investigation is part of
      ongoing research to improve the usefulness of hearing instruments and is also
      relevant in relation to other scientific investigations concerning the processing
      of sounds in complex acoustical environments by the human brain.

PMID- 21096239
TI  - Evaluation of an alternative definition for the apnea-hypopnea index.
AB  - The apnea-hypopnea index (AHI) plays a major role in determining whether a
      patient suffers from SAHS, as well as in evaluating the severity of his/her
      condition. To obtain this index the number of apneas and hypopneas that the
      patient has experienced during his/her sleep is calculated, and the result is
      divided by the number of hours of sleep. The standard definitions of apnea and
      hypopnea require that these events have a minimum temporal span of 10 seconds.
      Our experience has taught us that some respiratory airflow limitations lasting
      less than 10 seconds can produce a noticeable effect on the patient's blood
      oxyhemoglobin saturation (SpO2). In this paper we propose alternative definitions
      for apnea and hypopnea events that include respiratory airflow limitations with a
      temporal span between 5 and 10 seconds when they are associated with a drop in
      SpO2 of at least 3%. Then we compare the AHI calculated using the standard
      definition and our definition over a database of 40 polysomnograms. For 2 of the
      40 patients, the standard AHI clearly underestimates the severity of the
      patient's condition, while ours does not.

PMID- 21096240
TI  - Automatic K-complexes detection in sleep EEG recordings using likelihood
      thresholds.
AB  - In this paper, we present an automatic method for K-complexes detection based on
      features extraction and the use of fuzzy thresholds. The validity of our process
      was examined on the basis of two visual K-complexes scorings performed on 5
      excerpts of 30 minutes. Results were investigated through all different sleep
      stages. The algorithm provides global true positive rates of 61.72% and 60.94%,
      respectively with scorer 1 and scorer 2. The false positive proportions (compared
      to the total number of visually scored K-complexes) are of 19.62% and 181.25%,
      while the false positive rates estimated on a one 1 second resolution are only of
      0.53% and 1.53%. These results suggest that our approach is completely suitable
      since its performances are similar to those of the human scorers.

PMID- 21096241
TI  - Evolved fuzzy reasoning model for hypoglycaemic detection.
AB  - Hypoglycaemia is a serious side effect of insulin therapy in patients with
      diabetes. We measure physiological parameters (heart rate, corrected QT interval
      of the electrocardiogram (ECG) signal) continuously to provide early detection of
      hypoglycemic episodes in Type 1 diabetes mellitus (T1DM) patients. Based on the
      physiological parameters, an evolved fuzzy reasoning model (FRM) to recognize the
      presence of hypoglycaemic episodes is developed. To optimize the fuzzy rules and
      the fuzzy membership functions of FRM, an evolutionary algorithm called hybrid
      particle swarm optimization with wavelet mutation operation is investigated. All
      data sets are collected from Department of Health, Government of Western
      Australia for a clinical study. The results show that the proposed algorithm
      performs well in terms of the clinical sensitivity and specificity.

PMID- 21096242
TI  - Trial pruning for classification of single-trial EEG data during motor imagery.
AB  - Due to the artifacts in electroencephalography (EEG) data, the performance of
      brain-computer interface (BCI) is degraded. On the other hand, in the motor
      imagery based BCI system, EEG signals are usually contaminated by the misleading
      trials caused by improper imagination of a movement. In this paper, we present a
      novel algorithm to detect the abnormal EEG data using genetic algorithm (GA).
      After trial pruning, a subset of the EEG data are selected, on which common
      spatial pattern (CSP) and Gaussian classifier are trained. The performance of the
      proposed method is tested on Data set IIa of BCI Competition IV, and the
      simulation result demonstrates a significant improvement for six out of nine
      subjects.

PMID- 21096243
TI  - ECG Data-Acquisition and classification system by using wavelet-domain Hidden
      Markov Models.
AB  - This article is concerned with the classification of ECG pulses by using state of
      the art Continuous Density Hidden Markov Models (CDHMM's). The ECG signal is
      simultaneously observed at three different level of focus by means of the Wavelet
      Transform (WT). The types of beat being selected are normal (N), premature
      ventricular contraction (V) which is often precursor of ventricular arrhythmia,
      two of the most common class of supra-ventricular arrhythmia (S), named atrial
      fibrillation (AF), atrial flutter (AFL), and normal rhythm (N). Both MLII and V1
      derivations are used. Run time classification errors can be detected at the
      decoding stage if the classification of each derivation is different. These
      pulses are selected for a posterior physician analysis. Experimental results were
      obtained in real data from MIT-BIH Arrhythmia Database and also in data acquired
      from a developed low-cost Data-Acquisition System.

PMID- 21096244
TI  - Automatic segmentation of the cerebellum of fetuses on 3D ultrasound images,
      using a 3D Point Distribution Model.
AB  - Analysis of fetal biometric parameters on ultrasound images is widely performed
      and it is essential to estimate the gestational age, as well as the fetal growth
      pattern. The use of three dimensional ultrasound (3D US) is preferred over other
      tomographic modalities such as CT or MRI, due to its inherent safety and
      availability. However, the image quality of 3D US is not as good as MRI and
      therefore there is little work on the automatic segmentation of anatomic
      structures in 3D US of fetal brains. In this work we present preliminary results
      of the development of a 3D Point Distribution Model (PDM), for automatic
      segmentation, of the cerebellum in 3D US of the fetal brain. The model is
      adjusted to a fetal 3D ultrasound, using a genetic algorithm which optimizes a
      model fitting function. Preliminary results show that the approach reported is
      able to automatically segment the cerebellum in 3D ultrasounds of fetal brains.

PMID- 21096245
TI  - Improvement of speckle noise reduction using multi-resolutional coherence
      measurement in ultrasound image.
AB  - Ultrasound (US) images are degraded by speckle noise that reduces the contrast
      and details of images. But the effective method for speckle noise reduction with
      keeping edge has been still a challenging point. Coherence measurement has been
      used to distinguish homogeneous region and coherence regions, e.g. edges, and the
      edge map obtained from coherence measurement has limitation such as noisy or
      discontinued edge detection. In this paper, to overcome these problems, the
      enhanced edge map generation using multi-resolutional coherence measurement is
      proposed and adaptive wavelet based-speckle noise reduction is performed using
      the enhanced edge map. The experimental results showed that the enhanced edge map
      by proposed method contains the robust and linked edge information. Moreover, the
      results show that the proposed method outperforms the conventional method in
      preserving edge details.

PMID- 21096246
TI  - An additive and lossless watermarking method based on invariant image
      approximation and Haar wavelet transform.
AB  - In this article, we propose a new additive lossless watermarking scheme which
      identifies parts of the image that can be reversibly watermarked and conducts
      message embedding in the conventional Haar wavelet transform coefficients. Our
      approach makes use of an approximation of the image signal that is invariant to
      the watermark addition for classifying the image in order to avoid
      over/underflows. The method has been tested on different sets of medical images
      and some usual natural test images as Lena. Experimental result analysis
      conducted with respect to several aspects including data hiding capacity and
      image quality preservation, shows that our method is one of the most competitive
      existing lossless watermarking schemes in terms of high capacity and low
      distortion.

PMID- 21096247
TI  - Segmentation for classification of gastroenterology images.
AB  - Automatic classification of cancer lesions in tissues observed using
      gastroenterology imaging is a non-trivial pattern recognition task involving
      filtering, segmentation, feature extraction and classification. In this paper we
      measure the impact of a variety of segmentation algorithms (mean shift,
      normalized cuts, level-sets) on the automatic classification performance of
      gastric tissue into three classes: cancerous, pre-cancerous and normal.
      Classification uses a combination of color (hue-saturation histograms) and
      texture (local binary patterns) features, applied to two distinct imaging
      modalities: chromoendoscopy and narrow-band imaging. Results show that mean-shift
      obtains an interesting performance for both scenarios producing low
      classification degradations (6%), full image classification is highly inaccurate
      reinforcing the importance of segmentation research for Gastroenterology, and
      confirm that Patch Index is an interesting measure of the classification
      potential of small to medium segmented regions.

PMID- 21096248
TI  - Manual measurement of retinal bifurcation features.
AB  - This paper introduces a new computerized tool for accurate manual measurement of
      features of retinal bifurcation geometry, designed for use in investigating
      correlations between measurement features and clinical conditions. The tool uses
      user-placed rectangles to measure the vessel width, and lines placed along vessel
      center lines to measure the angles. An analysis is presented of measurements
      taken from 435 bifurcations. These are compared with theoretical predictions
      based on optimality principles presented in the literature. The new tool shows
      better agreement with the theoretical predictions than a simpler manual method
      published in the literature, but there remains a significant discrepancy between
      current theory and measured geometry.

PMID- 21096249
TI  - Multi scale and slice-based approach for automatic spine detection.
AB  - Dendritic spines play an essential role in the central nervous system. Recent
      experiments have revealed that neuron functional properties are highly correlated
      with the statistical and morphological changes of the dendritic spines. In this
      paper, we propose a new multi scale approach for detecting dendritic spines in a
      2D Maximum Intensity Projection (MIP) image of the 3D neuron data stacks
      collected from a 2-photon laser scanning confocal microscope. The proposed method
      utilizes the curvilinear structure detector in conjunction with the multi scale
      spine detection algorithm which automatically and accurately extracts and
      segments the spines with variational sizes along the dendrite. In addition, a
      slice-based spine detection algorithm is also proposed to detect spines which are
      hidden from the MIP image within the dendrite area. Experimental results show
      that our proposed method is effective for automatic spine detection and is able
      to accurately segment dendrite.

PMID- 21096250
TI  - Inter-Greedy technique for fusion of different carotid segmentation boundaries
      leading to high-performance IMT measurement.
AB  - User-based estimation of intima-media thickness (IMT) of carotid arteries leads
      to subjectivity in its decision support systems, while being used as a
      cardiovascular risk marker. During automated computer-based decision support, we
      had developed segmentation strategies that follow three main courses of our
      contributions: (a) signal processing approach combined with snakes and fuzzy K
      means (CULEXsa), (b) integrated approach based on seed and line detection
      followed by probability based connectivity and classification (CALEXsa), and (c)
      morphological approach with watershed transform and fitting (WS). We have
      extended this fusion concept by taking merits of these multiple boundaries, so
      called, Inter-Greedy (IG) approach. Starting from the technique with the overall
      least system error (the snake-based one), we iteratively swapped the vertices of
      the lumen-intima/media-adventitia (LI/MA) profiles until we minimized its overall
      distance with respect to ground truth. The fusion boundary was the IG boundary.
      The mean error of Inter-Greedy technique (evaluated on 200 images) yielded 0.32
      +/- 0.44 pixel (20.0 +/- 27.5 microm) for the LI boundary (a 33.3% +/- 5.6%
      improvement over initial best performing technique) and 0.21 +/- 0.34 pixel (13.1
      +/- 21.3 microm) for MA boundary (a 32.3% +/- 6.7% improvement). IMT measurement
      error for Greedy method was 0.74 +/- 0.75 pixel (46.3 +/- 46.9 microm), a 43.5%
      +/- 2.4% improvement.

PMID- 21096251
TI  - Morphological segmentation for sagittal plane image analysis.
AB  - This paper introduces a morphological image segmentation method by applying
      watershed transform with markers to scale-space smoothed images and furthermore
      provides images for clinical monitoring and analysis of patients. The database
      comprises sagittal plane images taken from a digital camera of patients submitted
      to Global Postural Reeducation (GPR) physiotherapy treatment. Orthopaedic
      specialists can use these segmented images to diagnose posture problems, assess
      physiotherapy treatment evolution and thus reduce diagnostic errors due to
      subjective analysis.

PMID- 21096252
TI  - Three dimensional template matching segmentation method for motile cells in 3D+t
      video sequences.
AB  - In this work, we describe a segmentation cell method oriented to deal with
      experimental data obtained from 3D+t microscopical volumes. The proposed
      segmentation technique takes advantage of the pattern of appearances exhibited by
      the objects (cells) from different focal planes, as a result of the object
      translucent properties and its interaction with light. This information allows us
      to discriminate between cells and artifacts (dust an other) with equivalent size
      and shape that are present in the biological preparation. Using a simple
      correlation criteria, the method matches a 3D video template (extracted from a
      sample of cells) with the motile cells contained into the biological sample,
      obtaining a high rate of true positives while discarding artifacts. In this work,
      our analysis is focused on sea urchin spermatozoa cells but is applicable to many
      other microscopical structures having the same optical properties.

PMID- 21096253
TI  - Pectoral muscle detection in mammograms based on polar coordinates and the
      shortest path.
AB  - The automatic detection and segmentation of the pectoral muscle in the medio
      lateral oblique view of mammograms is essential for further analysis of breast
      anormalies. However, it is still a very difficult task since the sizes, shapes
      and intensity contrasts of pectoral muscles change greatly from image to image.
      In this paper, an algorithm based on the shortest path on a graph is proposed to
      automatically detect the pectoral muscle contour. To overcome the difficulties of
      searching for the path between a lateral and the top margins of the image, this
      is first transformed, using polar coordinates. In the transformed image, the
      muscle boundary in amongst the shortest paths between the top and the bottom
      rows. A comprehensive comparison with manually-drawn contours reveals the
      strength of the proposed method.

PMID- 21096254
TI  - Airborne asbestos fibers detection in microscope images using re-initialization
      free active contours.
AB  - Breathing in asbestos fibers can lead to a number of diseases, the fibers become
      trapped in the lung and cannot be removed by either coughing or the person's
      immune system. Atmospheric concentrations of carcinogenic asbestos fibers, have
      traditionally been measured visually using phase contrast microscopy. However,
      because this measurement method requires great skill, and has poor
      reproducibility and objectivity, the development of automatic counting methods
      has been long anticipated. In this paper we proposed an automated fibers
      detection method based on a variational formulation of geometric active contours
      that forces the level set function to be close to signed distance function and
      therefore completely eliminates the need of the costly re-initialization
      procedure. The method was evaluated using a ground truth of 29 manually annotated
      images. The results were encouraging for the further development of the proposed
      method.

PMID- 21096255
TI  - CMOS/microfluidic Lab-on-chip for cells-based diagnostic tools.
AB  - We describe in this paper cells sensing and manipulation methods, as well as
      platforms based on Lab-on-chip devices. Among other contributions, new circuit
      and microfluidic techniques, and packaging methods are proposed for efficient
      cells manipulation and detection. The proposed devices include high-sensitivity
      sensing circuits (200 mV/fF), low-pressure liquid injection interfaces (< 0.65
      psi), low-voltage manipulation signals, direct-write microfluidic fabrication
      technique on top of CMOS based capacitive sensors. In addition, several types of
      electrode arrays (square and L-shaped) are used for the manipulation of various
      types of cells and particles.

PMID- 21096256
TI  - Automatic identification of internal carotid artery from 3DRA images.
AB  - Geometric characteristics and arrangement of the cerebral vessels are assumed to
      be related to the development of vascular diseases. Identifying anatomical
      segments and bifurcations of the cerebral vasculature allows the comparison of
      these characteristics across and within subjects. In this paper, we focus on the
      automatic identification of internal carotid artery (ICA) from 3D rotational
      angiographic images. The steps of the proposed method are the following: Arterial
      vascular tree is first segmented and centerlines are computed. From a set of
      centerlines, vascular tree topology is constructed and its bifurcations
      geometrically characterized. Finally, ICA terminal bifurcation is detected, which
      enables ICA identification. To detect ICA terminal bifurcation, a support vector
      machine classifier is trained. We processed 82 images to obtain 274 feature
      vectors of bifurcations around the ICA. 10*5-fold cross-validation showed an
      average accuracy of 99.6%, with 99.5% specificity and 100% sensitivity. The two
      most discriminating bifurcation features were: radius ratio between the smaller
      branch and its parent vessel, and the long-axis component of the smaller branch
      vector.

PMID- 21096257
TI  - Identification of lobar fissures in pathological lungs.
AB  - Identification of lobar fissures in human lungs is a non-trivial task due to
      their variable shape and appearance, along with the low contrast and high noise
      in computed tomographic (CT) images. Pathologies in the lungs can further
      complicate this identification by deforming and/or disrupting the lobar fissures.
      Current algorithms rely on the general anatomy of the lungs to find fissures
      affected by pathologies. This can be unreliable as deformations and/or
      disruptions of these fissures will alter the general lung anatomy. To overcome
      this, we developed an algorithm with the following novelties: (1) a new
      application of neural network based texture analysis to generalize fissure
      regions; and (2) a new method of fissure surface identification. We tested our
      algorithm on CT image stacks from 8 anonymous patients with pathological lungs.
      Compared to manually segmented fissures, our algorithm produced an average mean
      difference of 0.71 mm and 0.68 mm for identifying the left and right oblique
      fissures, respectively. Using a 3-mm percentile measure, the algorithm yielded an
      average accuracy of 86.8% for the left oblique fissure with a mean worst-case
      error of 3.18 mm. For the right oblique fissure, the algorithm produced an
      accuracy of 88.8% with a mean worst-case error of 3.13 mm. The above results show
      feasibility of using our algorithm for identifying fissures in pathological
      lungs.

PMID- 21096258
TI  - Automatic liver segmentation from CT scans based on a statistical shape model.
AB  - In this paper, we present an algorithm for automatic liver segmentation from CT
      scans which is based on a statistical shape model. The proposed method is a
      hybrid method that combines three steps: 1) Localization of the average liver
      shape model in a test CT volume via 3D generalized Hough transform; 2) Subspace
      initialization of the statistical shape model; 3) Deformation of the shape model
      to adapt to liver contour through an optimal surface detection approach based on
      graph theory. The proposed method is evaluated on MICCAI 2007 liver segmentation
      challenge datasets. The experiment results demonstrate availability of the
      proposed method.

PMID- 21096259
TI  - Learning-based approach for the automatic detection of the optic disc in digital
      retinal fundus photographs.
AB  - The optic disc is an important feature in the retina. We propose a method for the
      detection of the optic disc based on a supervised learning scheme. The method
      employs pixel and local neighbourhood features extracted from the ROI of a
      digital retinal fundus photograph. A support vector machine based classification
      mechanism is used to classify each image point as belonging to the cup and
      retina. The proposed method is evaluated on a sample image set of 68 retinal
      fundus images. The results show a high correlation (r>0.9) with the ground truth
      segmentation, with an overlap error of 6.02%, and found to be comparable to the
      inter-observer variability based on an independent second observer segmentation
      of the same data set.

PMID- 21096260
TI  - Automatic detection of posterior subcapsular cataract opacity for cataract
      screening.
AB  - Cataract is the leading cause of blindness and posterior subcapsular cataract
      (PSC) leads to significant visual impairment. An automatic approach for detecting
      PSC opacity in retro-illumination images is investigated. The features employed
      include intensity, edge, size and spatial location. The system was tested using
      441 images. The automatic detection was compared with the human expert. The
      sensitivity and specificity are 82.6% and 80% respectively. The preliminary
      research indicates it is feasible to apply automatic detection in the clinical
      screening of PSC in the future.

PMID- 21096262
TI  - Reference estimation in EEG recordings.
AB  - This work aims to analyze the reference (montage) problem in
      electroencephalographic (EEG) recordings. It is well accepted that EEG signals
      are a mixture of cerebral and extracerebral sources, and the solution to the
      reference problem depends on the hypothesized mixing model. We focus here on an
      acquisition model using a distant reference electrode and propose a method for
      determining and eliminating the reference signal which develops and improves Hu
      et al. work from [1]. The obtained solution, based on a constrained blind source
      separation (BSS) algorithm, outperforms the cited method on simulated noisy EEG
      signals for all noise levels.

PMID- 21096261
TI  - In vivo snapshot hyperspectral image analysis of age-related macular
      degeneration.
AB  - Drusen, the hallmark lesions of age related macular degeneration (AMD), are
      biochemically heterogeneous and the identification of their biochemical
      distribution is key to the understanding of AMD. Yet the challenges are to
      develop imaging technology and analytics, which respect the physical generation
      of the hyperspectral signal in the presence of noise, artifacts, and multiple
      mixed sources while maximally exploiting the full data dimensionality to uncover
      clinically relevant spectral signatures. This paper reports on the statistical
      analysis of hyperspectral signatures of drusen and anatomical regions of interest
      using snapshot hyperspectral imaging and non-negative matrix factorization (NMF).
      We propose physical meaningful priors as initialization schemes to NMF for
      finding low-rank decompositions that capture the underlying physiology of drusen
      and the macular pigment. Preliminary results show that snapshot hyperspectral
      imaging in combination with NMF is able to detect biochemically meaningful
      components of drusen and the macular pigment. To our knowledge, this is the first
      reported demonstration in vivo of the separate absorbance peaks for lutein and
      zeaxanthin in macular pigment.

PMID- 21096263
TI  - Multi-dimensional PARAFAC2 component analysis of multi-channel EEG data including
      temporal tracking.
AB  - The identification of signal components in electroencephalographic (EEG) data
      originating from neural activities is a long standing problem in neuroscience.
      This area has regained new attention due to the possibilities of multi
      dimensional signal processing. In this work we analyze measured visual-evoked
      potentials on the basis of the time-varying spectrum for each channel. Recently,
      parallel factor (PARAFAC) analysis has been used to identify the signal
      components in the space-time-frequency domain. However, the PARAFAC decomposition
      is not able to cope with components appearing time-shifted over the different
      channels. Furthermore, it is not possible to track PARAFAC components over time.
      In this contribution we derive how to overcome these problems by using the
      PARAFAC2 model, which renders it an attractive approach for processing EEG data
      with highly dynamic (moving) sources.

PMID- 21096265
TI  - Automatic artifact removal from EEG - a mixed approach based on double blind
      source separation and support vector machine.
AB  - Electroencephalography (EEG) recordings are often obscured by physiological
      artifacts that can render huge amounts of data useless and thus constitute a key
      challenge in current brain-computer interface research. This paper presents a new
      algorithm that automatically and reliably removes artifacts from EEG based on
      blind source separation and support vector machine. Performance on a motor
      imagery task is compared for artifact-contaminated and preprocessed signals to
      verify the accuracy of the proposed approach. The results showed improved results
      over all datasets. Furthermore, the online applicability of the algorithm is
      investigated.

PMID- 21096264
TI  - EEG sensor selection by sparse spatial filtering in P300 speller brain-computer
      interface.
AB  - A Brain-Computer Interface (BCI) is a specific type of human-machine interface
      that enables communication between a subject/patient and a computer by direct
      control from decoding of brain activity. This paper deals with the P300-speller
      application that enables to write a text based on the oddball paradigm. To
      improve the ergonomics and minimize the cost of such a BCI, reducing the number
      of electrodes is mandatory. We propose a new algorithm to select a relevant
      subset of electrodes by estimating sparse spatial filters. A l(1)-norm
      penalization term, as an approximation of the l(0)-norm, is introduced in the
      xDAWN algorithm, which maximizes the signal to signal-plus-noise ratio.
      Experimental results on 20 subjects show that the proposed method is efficient to
      select the most relevant sensors: from 32 down to 10 sensors, the loss in
      classification accuracy is less than 5%.

PMID- 21096266
TI  - Combining EMD with ICA for extracting independent sources from single channel and
      two-channel data.
AB  - Blind Source Separation (BSS) techniques are frequently needed in the processing
      of biomedical signals. This need comes from the fact that these signals are often
      composed of many different sources, which are mixed in the measured signal.
      However, we are usually only interested in examining one or a limited set of
      sources of interest separately. A variety of algorithms exist for separating
      multichannel mixtures into its independent sources (e.g. different Independent
      Component Analysis (ICA) techniques). These techniques only work if the number of
      channels is larger than, or equal to the number of sources present in the signal.
      On the other hand, only a few algorithms have been reported for the analysis of
      single channel sources, or other mixtures where the number of sources is higher
      than the number of channels. In this work we show a new technique which combines
      Empirical Mode Decomposition (EMD) and Independent Component Analysis (ICA). We
      will show that this technique is capable in separating independent sources when
      the number of these sources is higher than the number of channels available. We
      show the performance in single channel and two-channel biosignal processing.

PMID- 21096267
TI  - Sleep stage transitions in chronic fatigue syndrome patients with or without
      fibromyalgia.
AB  - Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained
      conditions that share considerable overlapping symptoms, including sleep-related
      complaints. However, differences between the two conditions have been reported,
      and we hypothesized that dynamic aspects of sleep, recently attracting scientific
      interests, would be different in the two groups of patients. We thus study
      transition probabilities between sleep stages of CFS patients with or without FM.
      Subjects were 26 healthy controls, 14 CFS patients without FM (CFS alone) and 12
      CFS patients with FM (CFS+FM) - all women. We studied transition probabilities
      between sleep stages (waking, REM sleep and Stage I, Stage II and slow-wave sleep
      (Stage III+IV)). We found that probabilities of transition from REM sleep to
      waking were significantly greater in CFS alone than in controls; we have reported
      previously this sleep disruption as the specific sleep problem for CFS alone
      [Kishi et al., 2008]. Probabilities of transitions from waking, REM sleep and
      Stage I to Stage II, and those from slow-wave sleep to Stage I, were
      significantly greater in CFS+FM than in controls; the former might indicate
      increased sleep pressure in CFS+FM and the latter may be the specific sleep
      problem of CFS+FM. These results suggest that CFS and FM are different illnesses
      associated with different problems of sleep regulation.

PMID- 21096268
TI  - Linear and nonlinear analysis of autonomic regulation of heart rate variability
      in healthy first-degree relatives of patients with schizophrenia.
AB  - The recently reported cardiac autonomic dysregulation in patients with
      schizophrenia is characterized by a decreased vagal and an increased sympathetic
      modulation. This impairment possibly contributes to the increased cardiovascular
      mortality rate that is up to three times higher in these patients than in general
      population. The aim of this study was to characterize the autonomic regulation in
      schizophrenia and to evidence for a genetic influence. We investigated 36
      patients with schizophrenia, 36 healthy first-degree relatives and 36 healthy
      controls. The autonomic regulation was classified applying linear and nonlinear
      methods of heart rate variability analysis. Healthy relatives were compared with
      healthy controls matched with respect to age and gender and with patients
      suffering from schizophrenia. Further on, schizophrenic patients were compared
      with healthy controls. The results show that the autonomic regulation in healthy
      relatives differs significantly from healthy controls (p<0.01) and slightly from
      patients. However, the most significant differences could be found between
      patients and healthy controls (p<0.0001). Relatives revealed decreased heart rate
      variability and demonstrated an altered autonomic modulation of heart rate and
      similar pattern of autonomic dysfunction as patients. This autonomic impairment
      found in relatives might indicate an underlying disease-inherent genetic
      vulnerability, especially since it is known that heart rate variability is
      partially under genetic control.

PMID- 21096269
TI  - Evaluation of an ECG heartbeat classifier designed by generalization-driven
      feature selection.
AB  - In this work we studied the classification performance of feature models selected
      with a floating algorithm, focusing in the generalization capability. The
      features were extracted from the RR interval series, from all ECG leads and
      different scales of the wavelet transform. The generalization was studied using
      Physionet databases. In all databases the AAMI recommendations for class labeling
      and results presentation were followed. A floating feature selection algorithm
      was used to obtain the best performing and generalizing models in the training
      and validation sets for different search configurations. The best model found
      includes 8 features, was trained in a partition of the MIT-BIH Arrhythmia
      database, and was evaluated in a completely disjoint partition of the same
      database. The results obtained were: global accuracy of 93%; for normal beats,
      sensitivity (S) 95%, positive predictive value (P+) 98%; for supraventricular
      beats, S 77%, P(+) 39%; for ventricular beats S 81%, P(+) 87%. This classifier
      model has less features and performs better than other state of the art methods
      with results suggesting better generalization capability.

PMID- 21096270
TI  - Development of a novel border detection method for melanocytic and non
      melanocytic dermoscopy images.
AB  - Computer aided diagnosis of dermoscopy images has shown great promise in
      developing a quantitative, objective way of classifying skin lesions. An
      important step in the classification process is the lesion segmentation. Many
      papers have been successful at segmenting melanocytic skin lesions (MSLs) but few
      have focused on non-melanocytic skin lesions (NoMSLs), since the wide variety of
      lesions makes accurate segmentation difficult. We developed an automatic
      segmentation program for the border detection of skin lesions. We tested our
      method on a set of 107 non-melanocytic lesions and on a set of 319 melanocytic
      lesions. Our method achieved precision/recall scores of 84.5% and 88.5% for
      NoMSLs, achieving higher scores than two previously published methods. Our method
      also achieved precision/recall scores of 93.9% and 93.8% for MSLs which was
      competitive or better than the two other methods. Therefore, we conclude that our
      approach is an accurate segmentation method for both melanocytic and non
      melanocytic lesions.

PMID- 21096271
TI  - Classification of melanocytic skin lesions from non-melanocytic lesions.
AB  - In this paper, we present a classification method of dermoscopy images between
      melanocytic skin lesions (MSLs) and non-melanocytic skin lesions (NoMSLs). The
      motivation of this research is to develop a pre-processor of an automated
      melanoma screening system. Since NoMSLs have a wide variety of shapes and their
      border is often ambiguous, we developed a new tumor area extraction algorithm to
      account for these difficulties. We confirmed that this algorithm is capable of
      handling different dermoscopy images not only those of NoMSLs but also MSLs as
      well. We determined the tumor area from the image using this new algorithm,
      calculated a total 428 features from each image, and built a linear classifier.
      We found only two image features, "the skewness of bright region in the tumor
      along its major axis" and "the difference between the average intensity in the
      peripheral part of the tumor and that in the normal skin area using the blue
      channel" were very efficient at classifying NoMSLs and MSLs. The detection
      accuracy of MSLs by our classifier using only the above mentioned image feature
      has a sensitivity of 98.0% and a specificity of 86.6% in a set of 107 non
      melanocytic and 548 melanocytic dermoscopy images using a cross-validation test.

PMID- 21096272
TI  - Design and control of a robotic system for assistive laser phonomicrosurgery.
AB  - This paper presents the design, implementation and control of a novel robotic
      system for assistive laser phonomicrosurgeries. The goals here are to improve the
      precision, the controllability, the safety and the ergonomics of traditional
      transoral laser laryngeal surgeries. Successful steps achieved by the developed
      system in those directions are presented here, including the design, control and
      characterization of a novel laser micromanipulator system. Such system is shown
      to achieve very fast (181mm/s) and accurate (1um resolution) laser beam aiming
      within an 11*11mm target area. The design and implementation of a high-level
      control system for safe operation of the new laser phonomicrosurgery equipment is
      also described in this paper. This controller runs on a personal computer,
      offering a comfortable and safe surgical environment for the surgeon. In
      addition, it implements safe teleoperation by allowing the definition of safe and
      exclusion zones for surgical laser aiming. Automation of ablation procedures is
      also implemented on this high-level controller and described here. This feature
      adds an extra level of safety for phonomicrosurgeries by allowing the precise
      execution of surgical plans defined by the surgeon.

PMID- 21096273
TI  - Target motion compensation in MRI-guided prostate biopsy with static images.
AB  - PURPOSE: MRI-guided prostate needle biopsy requires compensation for organ motion
      between target planning and needle placement. METHODS: We propose slice-to-volume
      registration algorithms for tracking the prostate motion. Three orthogonal intra
      operative slices are acquired in the approximate center of the prostate and
      registered with a high-resolution target planning volume. Both rigid and
      deformable scenarios were implemented. MRI-guided robotic prostate biopsy cases
      were analyzed retrospectively. RESULTS: Average registration errors were 2.55mm
      for the rigid algorithm and 2.05mm for the deformable algorithm. CONCLUSION:
      Slice-based tracking appears to be promising. Deformable registration does not
      seem warranted.

PMID- 21096274
TI  - Retinal vessel cannulation with an image-guided handheld robot.
AB  - Cannulation of small retinal vessels is often prohibitively difficult for
      surgeons, since physiological tremor often exceeds the narrow diameter of the
      vessel (40-120 microm). Using an active handheld micromanipulator, we introduce
      an image-guided robotic system that reduces tremor and provides smooth, scaled
      motion during the procedure. The micromanipulator assists the surgeon during the
      approach, puncture, and injection stages of the procedure by tracking the pipette
      and anatomy viewed under the microscope. In experiments performed ex vivo by an
      experienced retinal surgeon on 40-60 microm vessels in porcine eyes, the success
      rate was 29% (2/7) without the aid of the system and 63% (5/8) with the aid of
      the system.

PMID- 21096275
TI  - Targeting error simulator for image-guided prostate needle placement.
AB  - MOTIVATION: Needle-based biopsy and local therapy of prostate cancer depend
      multimodal imaging for both target planning and needle guidance. The clinical
      process involves selection of target locations in a pre-operative image volume
      and registering these to an intra-operative volume. Registration inaccuracies
      inevitably lead to targeting error, a major clinical concern. The analysis of
      targeting error requires a large number of images with known ground truth, which
      has been infeasible even for the largest research centers. METHODS: We propose to
      generate realistic prostate imaging data in a controllable way, with known ground
      truth, by simulation of prostate size, shape, motion and deformation typically
      encountered in prostatic needle placement. This data is then used to evaluate a
      given registration algorithm, by testing its ability to reproduce ground truth
      contours, motions and deformations. The method builds on statistical shape atlas
      to generate large number of realistic prostate shapes and finite element modeling
      to generate high-fidelity deformations, while segmentation error is simulated by
      warping the ground truth data in specific prostate regions. Expected target
      registration error (TRE) is computed as a vector field. RESULTS: The simulator
      was configured to evaluate the TRE when using a surface-based rigid registration
      algorithm in a typical prostate biopsy targeting scenario. Simulator parameters,
      such as segmentation error and deformation, were determined by measurements in
      clinical images. Turnaround time for the full simulation of one test case was
      below 3 minutes. The simulator is customizable for testing, comparing, optimizing
      segmentation and registration methods and is independent of the imaging
      modalities used.

PMID- 21096276
TI  - Application of the HeartLander crawling robot for injection of a thermally
      sensitive anti-remodeling agent for myocardial infarction therapy.
AB  - The injection of a mechanical bulking agent into the left ventricular (LV) wall
      of the heart has shown promise as a therapy for maladaptive remodeling of the
      myocardium after myocardial infarct (MI). The HeartLander robotic crawler
      presented itself as an ideal vehicle for minimally-invasive, highly accurate
      epicardial injection of such an agent. Use of the optimal bulking agent, a
      thermosetting hydrogel developed by our group, presents a number of engineering
      obstacles, including cooling of the miniaturized injection system while the robot
      is navigating in the warm environment of a living patient. We present herein a
      demonstration of an integrated miniature cooling and injection system in the
      HeartLander crawling robot, that is fully biocompatible and capable of multiple
      injections of a thermosetting hydrogel into dense animal tissue while the entire
      system is immersed in a 37 degrees C water bath.

PMID- 21096277
TI  - Needle steering system using duty-cycled rotation for percutaneous kidney access.
AB  - The authors present ongoing work on the use of a variable curvature flexible
      needle steering system to gain percutaneous access to the kidney for medical
      interventions. A nonlinear control law is introduced which drives the needle to
      track a predetermined planar path using a steering approach based on duty-cycled
      rotation during insertion. Renal access is performed in simulation and tested in
      vitro in a tissue phantom to validate the proposed control method.

PMID- 21096278
TI  - Computational hypothesis testing for neuromuscular systems.
AB  - Here, we promote the perspective that a computational model can be a rigorous
      crystallization of a hypothesis for the mechanisms generating observed data. We
      provide an example of using this approach to discriminate among hypotheses
      despite uncertainty in parameter values. Humans have been shown to produce non
      uniform patterns of force fluctuation when they exert force in different
      directions with the index finger. We computationally formulated two hypotheses
      for this observation based on different cost functions of muscle effort, and then
      stochastically explored the space of unknown parameters to convergence to
      generate probability distributions of predictions from each hypothesis. The
      observed data were not within the probability distribution for Hypothesis 1: the
      sum of muscle forces is minimized, but were within the corresponding distribution
      for Hypothesis 2: the sum of squared muscle forces is minimized. Therefore, this
      approach provides rigorous evidence that Hypothesis 2 can not be rejected in
      favor of Hypothesis 1. The advantages and pitfalls of this computational approach
      to hypothesis testing are discussed.

PMID- 21096279
TI  - Probabilistic musculoskeletal modeling of the knee: A preliminary examination of
      an ACL-reconstruction.
AB  - In this study, a detailed uncertainty analysis was performed to place probability
      limits on model predictions for both uninjured and ACL-reconstructed joints. We
      investigated the effect of uncertainty in connective tissue intrinsic properties
      on the predicted kinematics and kinetics of the human joint under combined
      quadriceps and external loading observed during the load acceptance phase of the
      gait cycle. Our findings indicated that, on average, the ACL-reconstruction
      procedure using a patellar tendon graft increased the tibiofemoral joint
      adduction and internal rotation angles over the load acceptance phase. Our
      findings highlight one of the main features of the current construct; that is,
      model predictions are described in terms of their probabilistic properties. In
      the context of surgical evaluations, such properties define the level of
      likelihood that a given intervention can recover normal joint function.

PMID- 21096280
TI  - Predictive simulation of gait in rehabilitation.
AB  - This paper aims at demonstrating the capabilities of predictive, computational
      simulations of gait in clinical applications. In particular, the gait with
      bilateral and unilateral Ankle Foot-Orthoses (AFO's) is investigated. The problem
      is formulated in an optimal control framework where optimal motion and neural
      excitations to the muscles are computed solely on the basis of an assumed
      optimality criterion and periodicity constraints. The enormous potential of the
      approach as well as some of the current limitations are discussed on the light of
      simulation results.

PMID- 21096281
TI  - Adaptive terminal sliding mode control of ankle movement using functional
      electrical stimulation of agonist-antagonist muscles.
AB  - This paper presents a robust control strategy which is based on synergistic
      combination of an adaptive controller with terminal sliding mode control (TSMC)
      for online control of ankle movement using functional electrical stimulation
      (FES) of dorsiflexor and plantar flexor muscles in paraplegic subjects. The major
      advantage of TSMC derives from the property of robustness to system uncertainties
      and external disturbances with fast convergence without imposing strong control
      force. To implement TSMC, a model of neuromusculoskeletal system should be
      presented in standard canonical form. In this work, we design an adaptive
      updating law to estimate the parameters of the model during online control
      without requiring offline learning phase. The experimental results on two
      paraplegic subjects show that the TSMC provides excellent tracking control for
      different reference trajectories and could generate control signals to compensate
      the effects of muscle fatigue and external disturbance.

PMID- 21096282
TI  - Model of postural control system applied in Parkinson's disease patients.
AB  - In this study a simple model of the postural control system is implemented and
      its parameters are adjusted to explain the differences between Parkinson's
      disease patient's measures and healthy young adult's measures by performing
      simulations of spontaneous sway with center-of-pressure traces. An optimization
      procedure was performed varying four parameters of the model. The best adjustment
      obtained was when the proportional and derivative factors where the same as for
      healthy young adults and noise level gain and force feedback gain varied
      independently. Differences in the latter parameter can be explained because of
      insufficient and slowed force production necessary to counteract perturbations in
      Parkinson's disease patients while the former may be due to noise in the sensory
      system that estimates the vertical deviation angle and/or perturbations in the
      execution of the movement.

PMID- 21096283
TI  - Model to estimate hamstrings behavior in cerebral palsy patients: as a pre
      surgical clinical diagnosis tool.
AB  - Crouch gait is the most common motion abnormality in children with cerebral palsy
      (CP). This paper presents a new biomechanical model based on a simple rescaling
      and adjustment to CP patients who develop crouch gait by subject-specific
      anthropometric data. The model estimates the length of hamstrings, as the
      distance between the origin and insertion of the muscle, and the velocity of
      shortening of hamstrings by the first derivative of the length with respect to
      time. This model has the potential to increase the benefits of three-dimensional
      biomechanical models as it can discriminate between short, spastic or normal
      hamstrings. The main advantage of this model in clinical use is that it does not
      require costly magnetic resonance imaging.

PMID- 21096284
TI  - Causal neuronal networks provide functional signatures of stimulus encoding.
AB  - Graphical models are powerful tools to infer statistical relationships between
      simultaneously observed random variables. Here, we used Dynamic Bayesian Networks
      (DBN) to infer causal relationships between simultaneously recorded neurons in
      the rat somatosensory (barrel) cortex in response to whisker stimulation. DBNs
      attempt to explain the activity of the observed neurons by searching for the best
      network connectivity that explains the observed data. The results demonstrate
      that the networks inferred for the same whisker are stable across multiple
      repeated trials. In contrast to networks obtained using classical cross
      correlograms, DBN was able to discriminate between direct and indirect
      connectivity. We also found strong consistency between the inferred connections
      and the sequence of neural firing relative to the stimulus onset.

PMID- 21096285
TI  - Changes of hippocampal CA3-CA1 population nonlinear dynamics across different
      training sessions in rats performing a memory-dependent task.
AB  - Delayed-nonmatch-to-sample (DNMS) task is memory-dependent. Hippocampal CA3 and
      CA1 cells were shown to be encoding the required spatial and temporal information
      to complete this task. In order to identify possible changes in neural population
      nonlinear dynamics during learning of the DNMS task, we have first modeled the
      input-output transformation of spike trains across brain subregions from learning
      animals using a multiple-input, multiple-output (MIMO) nonlinear dynamic model.
      The feedforward and feedback kernels describing the relations between hippocampal
      CA3 and CA1 subregions have shown significant changes at different training
      sessions.

PMID- 21096286
TI  - Quantitative analysis of neural plasticity in motorcortex during functional
      recovery post spinal cord injury.
AB  - The impact of spinal cord injury (SCI) on potential functional reorganization in
      neuronal populations in motor cortical areas remains unknown, though its
      influence on functional recovery may be significant. The cortical neuronal data
      was recorded from a monkey while it was trained to walk bipedally on a treadmill
      both before and after spinal cord injury. By using the correlation coefficients
      between different neurons, we constructed graphs for multiple steps in different
      sessions. The global efficiency of the graph was then calculated to investigate
      the effect of SCI on the neuronal activity patterns and how the correlation
      between the neurons changes as the functional recovery continued. Our results
      indicate that the observed significant changes in neuronal activity patterns in
      the motor cortex, although preliminary, suggest that the patterns of functional
      reorganization (neural plasticity) in motor areas of the cortex correlate and
      contribute to the functional recovery.

PMID- 21096287
TI  - A theory about a role of the hyper direct pathway in pattern expression by the
      basal ganglia.
AB  - The Basal Ganglia (BG) are a group of nuclei, in the brain of mammalians and
      other vertebrates, strongly connected with the cerebral cortex, thalamus and
      other brain areas. The BG are associated with several brain functions including
      learning and motor control. When there is cortical activation, there is a strong
      synchronization between BG and cortex, i.e. when a given task is being executed
      or in the case of Parkinson disease[1], [2]. If we consider the internal segment
      of the Globus Pallidus (GPi) there is synchronism between GPi-cortex at
      frequencies as low as 3Hz to as high as 85Hz [1], [3]. In the other hand, in a
      delta sleep or in an anesthetized case, a very low frequency correlation is
      observed (1-10 Hz), but no high frequency correlation between GPi-cortex [1],
      [2], [3]. It is unknown why this decorrelation happens. But It is agreement that
      when there is no pattern to select, like in delta sleep or with an anesthetized
      model, the BG network would maintain the GPi and cortex decorrelated at high
      frequencies. Many thalamus-BG and thalamus-BG-cortex loops are modulators of the
      BG activity. Particularly there exists an anatomic thalamus-BG loop, formed by
      GPi, intralaminar thalamic nuclei (IL) and Subthalamic Nucleus (STN) [4]. Using a
      computational model, based on an "Integrate and Fire" neural network, we analyzed
      the IL nucleus as a modulator of the so-called hyper direct pathway. Our results
      show that, in an anesthetic case, this thalamic path could be relevant to allow a
      high frequency decorrelated state between the GPi and cortex.

PMID- 21096288
TI  - Can we infer subthalamic nucleus spike trains from intranuclear local field
      potentials?
AB  - The subthalamic nucleus (STN) is one of the subcortical nuclei that constitute
      the basal ganglia and a pivotal point of their function and dysfunction. In this
      paper, we use intranuclear recordings, acquired intraoperatively during deep
      brain stimulation procedure, to investigate whether it is possible to infer STN
      spike trains using only the underlying local field potentials (LFPs). We regard
      the LFPs to be the input and the spikes to be the output of a simple Hammerstein
      Wiener model and we show that STN spikes can indeed be inferred from intranuclear
      LFPs, at least with moderate success. Our model, although not always reliable
      when predicting exact spike positions, shows a good accuracy in predicting the up
      to 1 kHz structure in STN spike trains. Hence, intranuclear LFPs can indeed hold
      useful information for predicting STN spiking activity.

PMID- 21096289
TI  - ATP consumption and neural electrical activity: a physiological model for brain
      imaging.
AB  - The relation between neural electrical activity and oxygen consumption is the key
      issue in almost all brain image modalities based on perfusion. Despite the large
      amount of physiological information available in the literature about the
      processes involved in neural activation, a practical, tractable and
      simultaneously accurate mathematical model to describe this relation is needed.

PMID- 21096290
TI  - A novel method to detect heart beat rate using a mobile phone.
AB  - Heart Beat Rate calculation has traditionally been conducted using specialized
      hardware most commonly in the form of pulse oximeters or Electrocardiogram
      devices. Even though these methods offer high reliability, they require the users
      to have special sensor to measure their heart rate. In this paper we propose a
      system capable of estimating the heart beat rate using just a camera from a
      commercially available mobile phone. The advantage of this method is that the
      user does not need specialized hardware and s/he can take a measurement in
      virtually any place under almost any circumstances. Moreover the measurement
      provided can be used as a tool for health coaching applications or effective
      telecare services aimed in enhancing the user's well being.

PMID- 21096291
TI  - An internet-based system for home monitoring of respiratory muscle disorders.
AB  - Home telemonitoring is of great interest in respiratory medicine where large
      numbers of people have long term conditions. We developed a telemedicine
      instrument for home monitoring of patients with disturbed respiratory muscles.
      The instrument measures the maximum inspiratory pressure (Pimax), the inspiratory
      time constant (tau(i)) and connects to the Internet through TCP/IP protocol. The
      instrument was evaluated by means of a comparative analysis in 18 normal
      individuals and 15 COPD patients. In close agreement with the pathophysiology, a
      reduction in Pimax (p < 0.0001) and an increase in tau(i) (p < 0.001) was
      observed in COPD patients. We concluded that the developed system could be a
      useful tool for the evaluation of inspiratory muscle and for the implementation
      of telemedicine services, contributing to reduce the costs of the assistance
      offered to patients with respiratory diseases.

PMID- 21096292
TI  - A mobile communications system for home-visit medical services: the Electronic
      Doctor's Bag.
AB  - In the present study, "Electronic Doctor's Bag" which is a tele-healthcare tool
      for home-visit medical service using the mobile communications environment has
      been proposed and evaluated by preliminary experiments. It was shown that its
      basic function was sufficiently evaluated by a few doctors and nurses but further
      improvement in portability and operability is required on the basis of much more
      opinions of medical and nursing professionals.

PMID- 21096293
TI  - A cardiod based technique to identify cardiovascular diseases using mobile phones
      and body sensors.
AB  - To prevent the threat of Cardiovascular Disease (CVD) related deaths, the usage
      of mobile phone based computational platforms, body sensors and wireless
      communications is proliferating. Since mobile phones have limited computational
      resources, existing PC based complex CVD detection algorithms are often
      unsuitable for wireless telecardiology applications. Moreover, if the existing
      Electrocardiography (ECG) based CVD detection algorithms are adopted for mobile
      telecardiology applications, then there will be processing delays due to the
      computational complexities of the existing algorithms. However, for a CVD
      affected patient, seconds worth of delay could be fatal, since cardiovascular
      cell damage is a totally irrecoverable process. This paper proposes a fast and
      efficient mechanism of CVD detection from ECG signal. Unlike the existing ECG
      based CVD diagnosis systems that detect CVD anomalies from hundreds of sample
      points, the proposed mechanism identifies cardiac abnormality from only 5 sample
      points. Therefore, according to our experiments the proposed mechanism is up to 3
      times faster than the existing techniques. Due to less computational burden, the
      proposed mechanism is ideal for wireless telecardiology applications running on
      mobile phones.

PMID- 21096294
TI  - Mobile middleware for wireless body area network.
AB  - This paper presents a flexible, efficient and lightweight Wireless Body Area
      Network (WBAN) Middleware. The Middleware is developed to bridge the
      communication between mobile device as a gateway and the sensor nodes, and
      therefore it shields the underlying sensor and OS/protocol stack away from the
      WBAN application layer. The middleware is coded in the form of lightweight
      dynamic link library, which allows the application developer to simply
      incorporate the middleware resource dynamic link library into their application
      and call the required functions (i.e. data acquisition, resource management and
      configurations). A showcase of the middleware deployment is exhibited at the end
      of the paper.

PMID- 21096295
TI  - Protein surface functional description.
AB  - The paper presents an image-oriented description of artificial and biological
      nanostructured surfaces, with applicability to the functional characterization of
      atom neighborhoods at the surface of proteins. The property which is considered
      is the hydrophobicity around each surface atom. The actual hydrophobicity
      distribution on the atoms that form an atom's vicinity is replaced by an
      equivalent hydrophobicity density distribution, computed in a standardized
      hexagonal or octagonal pattern around the atom. The purpose of this work is to
      create a database of molecular surfaces that will be used in several
      nanotechnology research fields.

PMID- 21096296
TI  - Health technopole: innovation applied to clinical engineering & health technology
      management education.
AB  - In the Peruvian Health System, Clinical Engineering does not exist as a topic of
      intervention. 59% of biomedical equipment is officially classified as
      operational, however next to apply the correct classification methodology and
      include security issues, only 10% of the equipment are suitable for use in
      patients. The serious consequences for patients, is opposite to the increased
      public investment in the health sector. Reversing this context leads to
      structural changes at all levels of the organization and they will be achievable
      only through an appropriate educational program. A strategy focused on joint of
      capacities called Health Technopole has managed to implement an innovative Model
      of Education in Healthcare Technology Management HTM and Clinical Engineering CE
      aimed at solving this problem. The proposal focused on strategies to strengthen
      the educational goals such as creating HTM & CE Units in hospitals, the
      implementation of the methodology: Problem Based Learning and Project Management
      in HTM & CE in classroom and on line courses. The process includes an effective
      interaction with global organizations through teleconferences, Internships,
      Workshops and Seminars. A key component was the sustained multidisciplinary
      approach. Health Technopole CENGETS is an expert adviser for the Ministry of
      Health and is called for trainings, design training programs for regional
      governments and also supports global organizations such as PAHO / WHO and ORAS /
      CONHU. The proposal of innovation applied to HTM & CE Education is effective and
      is a benchmark for similar countries.

PMID- 21096297
TI  - "Hands on" in bioengineering.
AB  - Several students of Bioengineering complain about the excess of theoretical
      classes and the difficulty to assimilate the subject taught. This article
      presents a strategy to mix theory and practice when teaching, thus motivating
      students to engage in their studies.

PMID- 21096298
TI  - Erasmus mundus programme: an european oportunity for students and scholars.
AB  - European Union through the management of the Executive Agency for Education,
      Audiovisual and Culture (EACEA) set up in 2004 a mobility program with the aim of
      promoting and enhancing European Higher Education. This first edition of the
      program, which went from 2004 to 2008, involved mainly Master's Courses. In this
      edition just European Institutions were able to take part of the applicant group
      of universities whereas just non-European students and scholars were provided
      with scholarships to attend these masters. However, the new edition of the
      Erasmus Mundus Programme (2009-2013), without changing its aim, has broadened its
      activities. Among others, the current Programme allows non-European institutions
      to join the applying partnership and has devoted part of the budget to also
      finance scholarships for European student and scholars enrolled in a Erasmus
      Mundus Master Course (EMMC). On the other hand it has enclosed the previous
      External Cooperation Window under the name of Action 2. It consists on a
      consortium of EU and non-EU universities and involves students and scholar
      exchanges. Non EU partners will go to EU institutions belonging to the
      partnership and EU partners will go to non EU institutions also partner in the
      consortium.

PMID- 21096299
TI  - The biomedical engineer as a driver for Health Technology innovation.
AB  - Health Technology has played a mayor role on most of the fundamental advances in
      medicine, in the last 30 years. Right now, beginning the XXI Century, it is well
      accepted that the most important revolution expected in Health Care is the
      empowerment of the individuals on their own health management. Innovation in
      health care technologies will continue being paramount, not only in the advances
      of medicine and in the self health management of patients but also in allowing
      the sustainability of the public health care becomes more important, the role of
      the biomedical engineer will turn to be more crucial for the society. The paper
      targets the development of new curricula for the Biomedical Engineers, The needs
      of evolving on his different fields in which the contribution of the Biomedical
      Engineer is becoming fundamental to drive the innovation that Health Care
      Technology Industry must provide to continue improving human health through cross
      disciplinary activities that integrate the engineering sciences with the
      biomedical sciences and clinical practice.

PMID- 21096300
TI  - HeartCycle: beyond building demonstrators. A structured approach to develop,
      implement and validate healthcare innovations in telemonitoring.
AB  - HeartCycle, running since March 2008, is an European Integrated Project aiming to
      provide innovations for the next generation of disease management solutions
      dedicated for cardiovascular disease patients. The appropriate remote management
      of such patients at home is seen as a promising solution to both, the delivery of
      innovative healthcare and the containment of future healthcare cost. Major
      challenges are the detection of negative health status trends in time, the
      appropriate decision support for professionals to react to such trends and
      supporting the motivation of patients to be compliant to treatment regimes and to
      adopt a beneficial lifestyle. In this paper an overview description of the
      HeartCycle process is presented which is a structured approach to develop,
      implement and validate healthcare innovations.

PMID- 21096301
TI  - CHRONIOUS: an open, ubiquitous and adaptive chronic disease management platform
      for chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD)
      and renal insufficiency.
AB  - CHRONIOUS is an highly innovative Information and Communication Technologies
      (ICT) research Initiative that aspires to implement its vision for ubiquitous
      health and lifestyle monitoring. The 17 European project partners are strictly
      working together since February 2008 to realize and open platform to manage and
      monitor elderly patients with chronic diseases and many difficulties to reach
      hospital centers for routine controls. The testing activities will be done in
      Italy and Spain involving COPD (Chronic Obstructive Pulmonary Disease) and CKD
      (Chronic Kidney Disease) patients, these being widespread and highly expensive in
      terms of social and economic costs. Patients, equipped by wearable technologies
      and sensors and interacting with lifestyle interfaces, will be assisted by
      healthcare personnel able to check the health record and critical conditions
      through the Chronious platform data analysis and decision support system.
      Additionally, the new ontology based literature search engine will help the
      clinicians in the standardization of care delivery process. This paper is to
      present the main project objectives and its principal components from the
      intelligent system point of view.

PMID- 21096302
TI  - Shift from physician-driven care to patient-managed self monitoring and care for
      chronic diseases related to metabolic disorders.
AB  - Dealing with a chronic disease and, more specifically, with Diabetes Mellitus and
      other metabolic disorders, represents a great challenge for care givers, patients
      and the Health Care Systems as their treatment requires continuous medical care
      and patient self management. The engagement of patients in the adoption of
      healthy lifestyles with a positive impact in the progression of their diseases is
      fundamental to avoid the appearance of chronic complications or co-morbidities.
      This paper presents the shift towards a patient self-managed care as a promising
      first step towards the solution of the difficulties that the European Health
      Systems are facing to handle Diabetes Mellitus, a disease that has already
      reached epidemic proportions worldwide.

PMID- 21096303
TI  - Tracking motor recovery in stroke survivors undergoing rehabilitation using
      wearable technology.
AB  - Quantitative assessment of motor abilities in stroke survivors undergoing
      rehabilitation can be a valuable feedback to guide the rehabilitation process.
      The Functional Ability Scale (FAS) part of Wolf Motor Function Test (WMFT) is
      used to evaluate movement quality during performance of a set of functional motor
      tasks. In this paper, we show that information collected using body worn sensors
      such as accelerometers during performance of functional motor tasks by stroke
      survivors can be used to build accurate classifiers of FAS scores for individual
      tasks. We perform feature selection to improve classification accuracy and show
      that it is possible to estimate the total FAS score from a subset of functional
      motor tasks taken from the WMFT.

PMID- 21096304
TI  - Preliminary design of a simple passive toe exercise apparatus with a flexible
      metal hydride actuator for pressure ulcer prevention.
AB  - In an aging society, social demands for home-based rehabilitation and assistive
      technologies by healthcare and welfare services are globally increasing. The
      progress of quality-of-life technologies and rehabilitation science is a very
      important and urgent issue for elderly and disabled individuals as well as for
      their caregivers. Thus, there is a substantial need to develop simple bedside
      apparatuses for both continuous exercise of joints and for power assistance for
      standing to prevent and manage disuse syndromes (e.g., pressure ulcers, joint
      contractures and muscular atrophy). Unfortunately, there are currently no
      commercially-available actuators compatible with the human requirements of
      flexibility, quietness, lightness and a high power-to-weight ratio. To fulfill
      the above demands, we have developed a novel actuation device using a metal
      hydride (MH) alloy and a laminate film, called the flexible MH actuator, as a
      human-friendly force generator for healthcare and welfare services. In this
      paper, we show the basic structure and characteristics of the flexible MH
      actuator used to create a passive exercise system for preventing disuse
      syndromes. To evaluate the efficiency of passive exercise for bedsore prevention,
      subcutaneous blood flow during passive exercise at common pressure-ulcer sites is
      measured by a laser blood flow meter. The force and range-of-motion angle
      required for a passive exercise apparatus is also examined with the help of a
      professional physical therapist. Based on these findings, a prototype of a
      passive exercise apparatus is fabricated using the flexible MH actuator
      technology, and its operation characteristics are preliminarily verified using a
      thermoelectric control system.

PMID- 21096305
TI  - Feasibility of a hybrid-FES system for gait restoration in paraplegics.
AB  - This paper proposes a new configuration for a hybrid-FES gait restoration system,
      and presents a combination of simulation and experiment that support the
      feasibility of the proposed approach. Gait simulation results are presented that
      indicate the majority of load bearing and the majority of power for gait is
      provided by the legs (i.e., quadriceps muscle stimulation). Based on these
      simulations, experiments on healthy subjects indicate that the gait restoration
      approach should be capable of providing long periods of locomotion unimpeded by
      quadriceps muscle fatigue.

PMID- 21096306
TI  - Portable and attachable tele-echography robot system: FASTele.
AB  - The purpose of this report is to propose portable and attachable tele-echography
      robot system: FASTele. Focused assessment with sonography for trauma (FAST) is
      important for patients who have shock by internal bleeding. However, the patient
      has little time, and transportation to a hospital may take too long. A system
      which enables FAST more quickly is required. Therefore, we aim to develop a tele
      echography (FAST) robot system that can be used by a paramedic easily for shock
      patient in ambulance or at injury scene. To develop the system, portability and
      usability (for paramedic) are significant issues. We developed a tele-echography
      robot system which has 4-DOF. The robot is attached to each roughly FAST areas of
      patient body (body-based set up) and remotely fine-tuned position by a specialist
      in a hospital. The robot can control the posture of probe by curvature rails. The
      mechanism that maintains passively the contact force between the probe and
      patient's body surface by using springs enables the robot small and lightweight.
      Feasibility experiments of FAST are reported.

PMID- 21096308
TI  - Development of conductive polymer with carbon nanotubes for regenerative medicine
      applications.
AB  - Multi-wall carbon nanotube (MWCNT)/polymer composites are hybrid materials that
      combine numerous mechanical, electrical and chemical properties and thus,
      constitute ideal biomaterials for a wide range of regenerative medicine
      applications. Although, complete dispersion of MWCNT in a polymer matrix has
      rarely been achieved, in this study we have studied the dispersibility of MWCNT
      in POSS-PCU, a novel polymer based on polyprolactone and polycarbonate
      polyurethane (PCU) with an incorporated polyhedral oligomeric silsesquioxane
      (POSS). Furthermore, we developed a computational model that can visualise MWCNTs
      in order to predict the range of dispersibility and provide a 3-D mathematical
      model that can predict the chemical concentration for ideal nanocomposites.

PMID- 21096307
TI  - Algorithms for target prediction for computer users with athetosis.
AB  - Athetosis is a movement disorder that afflicts numerous persons with cerebral
      palsy, resulting in significant problems in their control of computer interfaces.
      As a step toward increasing the efficiency of icon selection by computer users
      with athetosis, we have implemented three techniques to reduce the time of target
      acquisition: transition assistance via directional gain variation based on target
      prediction during initial movement toward the target, settling assistance via
      gain reduction when in the vicinity of a predicted target, and expansion of the
      predicted target as the cursor approaches it. The paper describes each method,
      and presents results from evaluation of each method using a closed-loop model of
      a human subject with athetosis, trained using recorded data, at three different
      severity levels.

PMID- 21096309
TI  - Spontaneous patterning obtained by evaporation of Human Elastin-like Polypeptide
      solutions.
AB  - The potential of producing patterned, bioactive coatings with Human Elastin-Like
      Polypeptides (HELPs) has been investigated. The physicochemical features of these
      compounds have evidenced some differences between the two recombinantly expressed
      products. By a device-free, simple route and avoiding the use of chemically
      unfriendly compounds, micropatterned surfaces with the ability to control cell
      behavior could be obtained. Thus, HELPs represent a very promising class of
      macromolecule for future applications in surface engineering.

PMID- 21096310
TI  - Osteogenic differentiation of mesenchymal stem cells could be enhanced by
      strontium.
AB  - Strontium is a newly developed drug for decreasing risks of hip or vertebral
      fractures in postmenopausal women. Experimental studies have suggested that
      Strontium could enhance new bone formation and decrease the bone resorption.
      Mesenchymal stem cell (MSC) is an important category of stem cells which possess
      the osteogenic differentiation potential and could be used in the bone and
      cartilage tissue engineering. Here we investigated the effects of strontium on
      the osteogenic differentiation process of MSC. We found that strontium could
      enhance the calcium deposition process and promote bone repair, through enhancing
      the osteogenic differentiation of MSC. This study could help to develop a new
      strategy to induce the MSC to differentiate into the osteogenic lineage.

PMID- 21096311
TI  - Cell Sheet Stiffness Sensing without taking out from culture liquid.
AB  - Stiffness could be an important index for evaluating the vitality of cell sheet.
      This paper challenges the measurement of stiffness of transparent cell sheet in
      culture liquid without taking it out from petri dish. The system is composed of a
      micro air nozzle for supplying an air jet and a regular reflective type laser
      sensor for measuring the the deformation of transparent cell sheet. This system
      is called as Cell Sheet Stiffness Sensing system (CS(3) system). When an air jet
      is given to a cell sheet in culture liquid, it pushes away the liquid toward the
      outer direction at initial phase and reaches the surface of cell sheet. Without
      any switching motion, the air jet continuously imparts a force to the surface of
      cell sheet so that the sensor can measure the stiffness of the cell sheet.

PMID- 21096312
TI  - The nucleus as a central structure in defining the mechanical properties of stem
      cells.
AB  - Manipulation of stem cells is one of the highest goals within biological sciences
      for the development of devices for the regeneration of injured tissues. In
      general, the mechanical properties of cells are nowadays recognized to play a
      role in many cellular phenotypes, including mobility though tissues, survival to
      mechanical loading and differentiation. Here we present a study where the
      mechanics of bone marrow CD34+ hematopoietic stem cells (CD34+ cells) and bone
      marrow stromal cells (BMSCs) is investigated through micropipette aspiration. The
      objective was to address the role of the nucleus as a central mechanoactive
      structure in stem cells. Stem cell nuclei occupy most of the cell volume and
      present different properties from what is known for somatic cells. Mechanics
      revealed to be highly dependent on the nucleus, where CD34+ cells revealed to be
      stiffer than BMSCs for short times under loading assuming elastic behavior and
      highly viscoelastic for longer times under loading, which present a higher
      nuclear volume per cell volume ratio. Mechanics was also evaluated for
      agglomerates of stem cells by aspirating spheres of neural progenitor cells (NSC
      Ss). Relatively to single cells, NSC-Ss presented higher deformability, which
      seems to be more dependent on intracellular connectivity than on cell mechanics.
      The general character of the reported conclusions is being investigated with
      other types of stem cells.

PMID- 21096313
TI  - Review of studies on modulating enzyme activity by low intensity electromagnetic
      radiation.
AB  - This paper is a compilation of our findings on non-thermal effects of
      electromagnetic radiation (EMR) at the molecular level. The outcomes of our
      studies revealed that that enzymes' activity can be modulated by external
      electromagnetic fields (EMFs) of selected frequencies. Here, we discuss the
      possibility of modulating protein activity using visible and infrared light based
      on the concepts of protein activation outlined in the resonant recognition model
      (RRM), and by low intensity microwaves. The theoretical basis behind the RRM
      model expounds a potential interaction mechanism between electromagnetic
      radiation and proteins as well as protein-protein interactions. Possibility of
      modulating protein activity by external EMR is experimentally validated by
      irradiation of the L-lactate Dehydrogenase enzyme.

PMID- 21096314
TI  - A biomimetic three-layered compartmented scaffold for vascular tissue
      engineering.
AB  - Tissue engineering of vascular grafts still presents several shortcomings. Aiming
      to vascular regeneration, we developed a biomimetic multilayered scaffold with a
      middle pivotal collagen lamina between two functionalized layers of poly-L
      lactide by means of electrospinning technique, with oriented drug-delivery
      capacity for the differentiation of human mesenchymal stem cells seeded therein.
      Applying appropriate cytokines, the inner layer is able to act as a drug delivery
      system in order to generate a pro-angiogenic and anti-thrombotic environment and
      the outer one is used to induce the media and adventitia generation. Our findings
      are consistent with an adequate cell engrafting and a double type of
      differentiation in each side of the scaffold, in particular cells exhibited
      morphostructural changes resulting in the achievement of an endothelial-like
      phenotype in cells populating the inner side of the scaffold and SMA positivity
      with cell elongation resembling muscular phenotype in the cells of the outer
      layer. The proposed "smart" vascular bio-prosthesis will recapitulate the
      structure and microenvironment of native cardiovascular tissues. It could
      surmount many hurdles to clinical use and would be relevant for therapeutic
      applications in a variety of medical fields.

PMID- 21096315
TI  - A G-CSF functionalized PLLA scaffold for wound repair: An in vitro preliminary
      study.
AB  - Targeting wound repair, we developed an electrospun poly-L-lactide fibrous
      scaffold functionalized with G-CSF, a growth factor which is widely recognized as
      important in wound healing homeostasis. The scaffold was characterized in terms
      of morphology, mechanical properties and in vitro capacity to induce organization
      of co-cultures of murine fibroblasts and keratinocytes into a dermo-epidermal
      multilayered structure. Our findings are consistent with the promotion of a
      nonhostile environment, in which seeded cells could arrange themselves in an
      appropriate topographic distribution of elements at different levels of
      maturation up to a cornified epithelium on the top layer, resembling native skin.

PMID- 21096316
TI  - Spectral analysis of single-channel airflow and oxygen saturation recordings in
      obstructive sleep apnea detection.
AB  - This study investigated the usefulness of the very low spectral content of single
      channel airflow recordings to help in the diagnosis of the obstructive sleep
      apnea (OSA) syndrome. Additionally, we evaluated whether airflow frequency
      components in the 0.01 - 0.10 Hz band are linked with desaturations in blood
      oxygen saturation (SaO(2)) recordings due to apnea events. The relationship
      between changes in airflow and SaO(2) was analyzed by means of the magnitude
      squared coherence (MSC) function. Power spectral density (PSD) was used to obtain
      the power spectrum of single airflow and SaO(2) signals. Peak amplitude (PA) and
      relative power (P(R)) were used to parameterize the power spectrum in the very
      low frequency band. 148 subjects suspected of suffering from OSA were studied.
      Significant differences (p-value ? 0.01) between OSA positive and OSA negative
      subjects were obtained from PSD and MSC features. We found a power increase in
      the very low frequency band of single-channel airflow linked with the periodic
      desaturations of OSA. Diagnostic sensitivity, specificity and accuracy of 84.0%,
      85.4% and 84.5%, respectively, were reached with the peak amplitude of the
      airflow PSD. Thus, spectral features from the very low frequency components of
      single-channel airflow recordings could provide useful information to help in OSA
      diagnosis.

PMID- 21096317
TI  - Evaluation of feature extraction techniques on event-related potentials for
      detection of attention-deficit/hyperactivity disorder.
AB  - Event-related potentials (ERPs) are one of the most informative and dynamic
      methods of monitoring cognitive processes, which are widely used in clinical
      research to deal a variety of psychiatric and neurological disorders as attention
      deficit/hyperactivity disorder (ADHD). This work proposes an extraction and
      selection methodology for discriminating between normal and pathological patients
      with ADHD by using ERPs. Three different sets of features (morphological,
      wavelets, and nonlinear based) are analyzed, looking for the best classification
      accuracy. The results show that the wavelet features provided a good
      discriminative capability, but it improved by combining all the set of features
      and applying a feature selection algorithm, reaching a maximum accuracy rate of
      91.3%.

PMID- 21096318
TI  - Computer-mediated emotional regulation: detection of emotional changes using non
      parametric cumulative sum.
AB  - It has been demonstrated that negative emotions have adverse effects on the
      immune system of a person. This contributes to increased morbidity and mortality
      in the elderly population and has a direct impact on quality of life. Positive
      emotions on the other hand may not only undo the harmful effects of negative
      emotions but also protect against certain diseases. Hence the use of technology
      to facilitate emotional regulation that reduces negative emotions may be a good
      way to promote self-care and support well-being. In this paper we present the
      early design stages of an emotion detection system that aims to support remote
      support and self-regulation in situations of intense emotional distress. We
      provide evidence of the suitability of non-parametric cumulative sum (CUSUM) to
      indentify emotional changes from neutral to non-neutral and vice versa in real
      time.

PMID- 21096319
TI  - Wireless remote monitoring of atrial fibrillation using reconstructed 12-lead
      ECGs.
AB  - Remote surveillance is important for patients with atrial fibrillation (AF).
      Atrial signal recognition with conventional monitoring devices is difficult;
      remote AF detection is predominantly accomplished by R-R interval analysis.
      Twelve lead ECG (12L) displays atrial activity and remains the gold standard for
      AF diagnosis. CardioBip is a portable wireless patient-activated event monitor
      providing signal reconstruction of a 12L waveform (12CB) using 5 leads and
      patient-specific transformation matrices. We hypothesized that atrial signal
      analysis with 12CB can detect atrial activity and improve AF detection. METHODS:
      18 patients with AF undergoing DC cardioversion (CV) were studied. Separate 12
      lead P and QRS patient-specific transformation matrices were created at baseline
      AF. Multiple wireless 12CB transmissions were performed 3-7 days before and up to
      2 weeks after CV. Rhythm was confirmed with 12-lead ECGs (12L). In SR the number
      of leads with visible P waves (atrial signal > 0.05 mV), and P wave polarity were
      analyzed. In AF, the number of leads with AF signal were compared (fibrillatory
      [f] waves >0.025 mV). RESULTS: Fourteen of 18 patients successfully cardioverted
      to SR and 4 failed; thus, 14 SR and 22 AF transmissions were analyzed. SR P wave
      was visible on 141/168 leads on 12L and 137/168 on 12CB (126 true pos [TP] and 11
      false pos [FP] relative to 12L; p=0.26). In 126 leads with P waves in both 12L
      and 12CB, the methods agreed on P wave polarity in 125. In AF, F waves were
      visible in 178/264 leads on 12L and 189/264 leads on 12CB (144 TP, 45 FP;
      p=0.27). All 5 AF relapses were successfully detected by 12CB based on atrial
      activity. CONCLUSION: 12CB is not inferior to 12L in detecting atrial signal in
      SR and AF, and shows excellent potential for remote wireless monitoring of AF
      patients.

PMID- 21096320
TI  - Extracting footfalls from voxel data.
AB  - In this paper, we present a method for extracting footfall locations from three
      dimensional voxel data created from a pair of silhouettes. With the growth of the
      elderly population, there is a need for passive monitoring of physical activity
      to allow older adults to continue living in independent settings. Prior research
      using anonymized video data has shown good results in passively acquiring
      information useful for assessing physical function; and, additionally, research
      has shown that video data anonymized through the use of silhouettes alleviates
      privacy concerns of older adults towards the technology. Previous work in
      acquiring gait information from voxel data has not included a technique for
      identifying individual footfall locations, from which additional information
      useful for assessing asymmetric gait patterns and other physical parameters may
      be obtained. Furthermore, visualization of the footfall locations during a
      walking sequence may provide additional insight to care providers for assessing
      physical function. To evaluate our approach, participants were asked to walk
      across a GAITRite electronic mat, used to validate our results, while also being
      monitored by our camera system. Results show good agreement between the footfalls
      extracted by our system and those from the GAITRite.

PMID- 21096321
TI  - DiseaseAtlas: multi-facet visual analytics for online disease articles.
AB  - Online health information portals provide valuable content to casual consumers.
      However, the page-oriented nature of these resources makes it difficult for users
      to understand the overall information space and navigate the complex
      relationships between various diseases. We have developed a visual analytic
      system named DiseaseAtlas that helps users navigate a large set of disease
      related documents and understand multi-dimensional relationships for key semantic
      concepts such as symptoms and treatments. This paper describes several unique
      aspects of DiseaseAtlas and demonstrates its capabilities through a case study.

PMID- 21096322
TI  - Compressive sensing: from "compressing while sampling" to "compressing and
      securing while sampling".
AB  - In a traditional signal processing system sampling is carried out at a frequency
      which is at least twice the highest frequency component found in the signal. This
      is in order to guarantee that complete signal recovery is later on possible. The
      sampled signal can subsequently be subjected to further processing leading to,
      for example, encryption and compression. This processing can be computationally
      intensive and, in the case of battery operated systems, unpractically power
      hungry. Compressive sensing has recently emerged as a new signal sampling
      paradigm gaining huge attention from the research community. According to this
      theory it can potentially be possible to sample certain signals at a lower than
      Nyquist rate without jeopardizing signal recovery. In practical terms this may
      provide multi-pronged solutions to reduce some systems computational complexity.
      In this work, information theoretic analysis of real EEG signals is presented
      that shows the additional benefits of compressive sensing in preserving data
      privacy. Through this it can then be established generally that compressive
      sensing not only compresses but also secures while sampling.

PMID- 21096323
TI  - Detection of premature ventricular beats in ECG records using bayesian networks
      involving the P-Wave and fusion of results.
AB  - This article proposes to use the Bayesian network (BN) framework to support
      medical decision in the problem of heart beat classification in long-term
      electrocardiogram (ECG) records. The motivation to use the BN approach is to take
      into account the uncertainty present in the clinical reasoning. The case study is
      the classification of Premature Ventricular Beats (PVC). Specifically speaking,
      it is discussed the use of the P-Wave as a network node, to check its capability
      to improve the performance of the PVC classification. In spite of concluding that
      the P wave is not definitive for the classification, such results have motivated
      the main proposal of this work: a fusion of the results obtained by training the
      implemented BN with two distinct datasets, which has indeed improved the system
      performance.

PMID- 21096324
TI  - Similarity retrieval of cardiac reports.
AB  - Mining medical reports can reveal important information correlating diagnosis
      with raw measurements helping in decision support. In this paper we address the
      problem of finding similar measurement reports for aiding clinical decision
      support. Specifically, we present a new approach to generating document class
      models for measurement reports using a multi-scale feature-value kernel. The
      class models serve as natural feature selection mechanism as well as indexes to
      large report collections. A document retrieval algorithm based on document class
      models is presented to enable similarity retrieval of pre-diagnosed reports.
      Collaborative filtering-guided assembly of associated disease labels is used to
      achieve clinical decision support.

PMID- 21096325
TI  - Robust channel identification scheme: solving permutation indeterminacy of ICA
      for artifacts removal from ECG.
AB  - In this paper we propose a novel channel identification scheme for solving
      permutation indeterminacy introduced by Independent Component Analysis (ICA) for
      artifacts removal from recorded three channel ECG signals within the remote
      health monitoring environment. The proposed scheme does not depend on the
      definition of any specific artifact which is the case with the existing approach
      and therefore leads to more robust and generic solution to this problem. The
      proposed scheme has been validated using nine practical case studies and its
      robustness has been proved by comparison with the existing approach. Simulation
      results show that the proposed scheme works successfully for all the nine cases
      whereas the existing approach fails to identify the correct channel for four
      cases.

PMID- 21096326
TI  - Modeling of medical care with stochastic Petri Nets.
AB  - Due to the need for management, control, and monitoring of information in an
      effient way. The hospital automation has been the object of a number of studies
      owing to constantly evolving technologies. However, many hospital processes are
      still manual in private and public hospitals. Thus, the aim of this study is to
      model and simulate of medical care provided to patients in the Intensive Care
      Unit (ICU), using stochastic Petri Nets and their possible use in a number of
      automation processes.

PMID- 21096327
TI  - Localization of spontaneous magnetoencephalographic activity of neonates and
      fetuses using independent component and Hilbert phase analysis.
AB  - The fetal magnetoencephalogram (fMEG) is measured in the presence of large
      interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These
      cardiac interferences can be attenuated by orthogonal projection (OP) technique
      of the corresponding spatial vectors. However, the OP technique redistributes the
      fMEG signal among the channels and also leaves some cardiac residuals (partially
      attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this
      paper, we propose a novel way to extract and localize the neonatal and fetal
      spontaneous brain activity by using independent component analysis (ICA)
      technique. In this approach, we perform ICA on a small subset of sensors for 1
      min duration. The independent components obtained are further investigated for
      the presence of discontinuous patterns as identified by the Hilbert phase
      analysis and are used as decision criteria for localizing the spontaneous brain
      activity. In order to locate the region of highest spontaneous brain activity
      content, this analysis is performed on the sensor subsets, which are traversed
      across the entire sensor space. The region of the spontaneous brain activity as
      identified by the proposed approach correlated well with the neonatal and fetal
      head location. In addition, the burst duration and the inter-burst interval
      computed for the identified discontinuous brain patterns are in agreement with
      the reported values.

PMID- 21096328
TI  - The behavior of action potential conduction velocity on isokinetic knee extension
      tests.
AB  - The present study investigates the behavior of action potential conduction
      velocity (CV) on each repetition of an isokinetic test set and on each set as a
      whole. A total of seven healthy men (27.7 +/- 2.8 yrs, 1.74 +/- 0.06 m, and 79.6
      +/- 11.0 Kg) performed 3 (three) sets of 10 (ten) maximal concentric repetitions
      of dominant knee extension at 60 degrees /s on an isokinetic dynamometer, with 1
      minute of rest interval between the sets. The surface electromyographic (SEMG)
      signals were recorded from the vastus lateralis muscle during the exercises. CV
      was estimated with a spectral matching method which requires the SEMG acquisition
      technique based on a flexible linear array of electrodes (here used with 8
      electrodes and 5 mm inter-electrode distance). With the view to minimize the
      factors other than fatigue that also influence the CV behavior, only the
      extension phase of the isokinetic exercise repetition was considered for
      measurements. Results showed that CV usually increases during a single repetition
      whereas it has a decreasing tendency along the isokinetic set seen as a whole.

PMID- 21096329
TI  - SigMate: A MATLAB-based neuronal signal processing tool.
AB  - Advances in neuronal probe technology to record brain activity have posed a
      significant challenge in performing necessary processing and analysis of the
      recorded data. To be able to infer meaningful conclusions from the recorded
      signals through these probes, sophisticated signal processing and analysis tools
      are required. This paper presents a MATLAB-based novel tool, 'SigMate', capable
      of performing various processing and analysis incorporating the available
      standard tools and our in-house custom tools. The present features include, data
      display (2D and 3D), baseline correction, stimulus artifact removal, noise
      characterization, file operations (file splitter, file concatenator, and file
      column rearranger), latency estimation, determination of cortical layer
      activation order, spike detection, spike sorting, and are gradually growing. This
      tool has been tested extensively for the recordings using the standard
      micropipettes as well as implantable neural probes based on EOSFETs (Electrolyte
      Oxide-Semiconductor Field Effect Transistors) and will be made available to the
      community shortly.

PMID- 21096330
TI  - Signal processing system to quantify bilirubin in the jaundice clinical model
      spectra.
AB  - Neonatal jaundice is a medical condition which occurs in newborns as a result of
      an imbalance between the production and elimination of bilirubin. Excess
      bilirubin in the blood stream diffuses into the surrounding tissue leading to a
      yellowing of the skin. An optical system integrated with a signal processing
      system is used as a platform to noninvasively quantify bilirubin concentration
      through the measurement of diffuse skin reflectance. Initial studies, based on
      simulated skin reflectance spectra have lead to the generation of a clinical
      model for neonatal jaundice which, generates spectral reflectance data for
      jaundiced skin with varying levels of bilirubin concentration in the tissue. The
      spectral database built using the jaundice clinical model is then used as a test
      database to validate the signal processing system in real time. This evaluation
      forms the basis for understanding the translation of this research to human
      trials. The new jaundice clinical model and signal processing system have been
      successful validated using a porcine model as a surrogate for neonatal skin
      tissue. Samples of pig skin were soaked in bilirubin solutions of varying
      concentrations to simulate jaundice skin conditions. The resulting skins samples
      were analyzed with our skin reflectance systems producing bilirubin concentration
      values that show a high correlation (R(2) = 0.96) to concentration of the
      bilirubin solution that each porcine tissue sample was soaked in..

PMID- 21096331
TI  - Hybrid EEG-EOG brain-computer interface system for practical machine control.
AB  - Practical issues such as accuracy with various subjects, number of sensors, and
      time for training are important problems of existing brain-computer interface
      (BCI) systems. In this paper, we propose a hybrid framework for the BCI system
      that can make machine control more practical. The electrooculogram (EOG) is
      employed to control the machine in the left and right directions while the
      electroencephalogram (EEG) is employed to control the forword, no action, and
      complete stop motions of the machine. By using only 2-channel biosignals, the
      average classification accuracy of more than 95% can be achieved.

PMID- 21096332
TI  - Fourier and wavelet spectral analysis of EMG signals in supramaximal constant
      load dynamic exercise.
AB  - Frequency domain analyses of changes in electromyographic (EMG) signals over time
      are frequently used to assess muscle fatigue. Fourier based approaches are
      typically used in these analyses, yet Fourier analysis assumes signal
      stationarity, which is unlikely during dynamic contractions. Wavelet based
      methods of signal analysis do not assume stationarity and may be more appropriate
      for joint time-frequency domain analysis. The purpose of this study was to
      compare Short-Time Fourier Transform (STFT) and Continuous Wavelet Transform
      (CWT) in assessing muscle fatigue in supramaximal constant load dynamic exercise
      (110% VO(2peak)). The results of this study indicate that CWT and STFT analyses
      give similar fatigue estimates (slope of median frequency) in supramaximal
      constant load dynamic exercise (P>0.05). However, the results of the variance was
      significantly lower for at least one of the muscles studied in CWT compared to
      STFT (P < 0.05) indicating more variability in the EMG signal analysis using
      STFT. Thus, the stationarity assumption may not be the sole factor responsible
      for affecting the Fourier based estimates.

PMID- 21096333
TI  - Dynamic characteristics between the subjective score of motion sickness
      discomfort and video global motion.
AB  - It is well-known that visually-induced motion sickness (VIMS) is caused by image
      motion. Therefore it is important to clarify the relationship between image
      motion and the change in discomfort level. However, it is difficult to know the
      quick change in the level of discomfort during watching actual video image. The
      authors have proposed a method of interpolation for the subjective score, which
      has low time and quantitative resolutions, by using physiological parameters. The
      model which represents the change in subjective score of VIMS was expressed as
      multiple regression equations in which input parameters are cardiovascular
      indices such as heart rate variability. In this study, the model which represents
      the relation between global motion vectors of a video image and estimated
      subjective score was identified as ARX model. The results indicated that the
      simple ARX model can estimate the change in subjective score from global motion
      vectors.

PMID- 21096334
TI  - Predicting the neurodevelopmental outcome in newborns with hypoxic-ischaemic
      injury.
AB  - The prediction of outcome in newborns with hypoxic ischemic encephalopathy (HIE)
      is a problematic task. Here, the ability of a combination of clinical, heart rate
      and EEG measures to predict outcome at 2 years is investigated. One hour of EEG
      and ECG recordings were obtained from newborns 24 hours after birth. Each newborn
      was reassessed at 24 months to investigate their neurodevelopmental outcome. From
      the EEG and ECG recordings, a set of 12 features was extracted. To classify each
      baby's outcome this data, along with clinical information was fed to a support
      vector machine. On a per patient basis an ROC area of 0.768 was achieved with
      73.68% of newborns being assigned the correct outcome. Overall, this system
      presents a promising step towards the use of multimodal data for the prediction
      of neurodevelopmental outcome in newborns with HIE.

PMID- 21096335
TI  - Comparison of speech processing strategies for the design of an ultra low-power
      analog bionic ear.
AB  - Miniaturizing area and power consumptions of cochlear prosthetic devices is
      strongly required for full implantation. In this paper, several speech encoding
      strategies are studied and compared in order to find a compact speech processor
      that allows for full implantation and is able to convey both time and frequency
      components of the incoming speech to a set of electrical pulse stimuli. The study
      covers the widely recognized continuous time interleaved sampling (CIS) and
      strategies that convey the temporal fine structure (TFS), including race-to-spike
      asynchronous interleaved sampling (AIS), phase-locking (PL) using zero-crossing
      detection (ZCD), and PL using a peak-picking (PP) technique. To estimate the
      performances of the four systems, a spike-based reconstruction algorithm is
      employed to retrieve the original sounds after being processed by different
      strategies. The correlation factors between the reconstructed and original
      signals imply that strategies that convey TFS outperform CIS. Among them, the
      peak picking technique combines good performance with great compactness since
      envelope detectors are not required.

PMID- 21096336
TI  - Optimal FES parameters based on mechanomyographic efficiency index.
AB  - Functional electrical stimulation (FES) can artificially elicit movements in
      spinal cord injured (SCI) subjects. FES control strategies involve monitoring
      muscle features and setting FES profiles so as to postpone the installation of
      muscle fatigue or nerve cell adaptation. Mechanomyography (MMG) sensors register
      the lateral oscillations of contracting muscles. This paper presents an MMG
      efficiency index (EI) that may indicate most efficient FES electrical parameters
      to control functional movements. Ten healthy and three SCI volunteers
      participated in the study. Four FES profiles with two FES sessions were applied
      with in-between 15min rest interval. MMG RMS and median frequency were inserted
      into the EI equation. EI increased along the test. FES profile set to 1kHz pulse
      frequency, 200epsilons active pulse duration and burst frequency of 50Hz was the
      most efficient.

PMID- 21096337
TI  - Real-time detection of auditory steady-state responses.
AB  - Detection of the auditory steady-state responses (ASSRs) is a difficult task, its
      main technical impediment is no other than the excessively lengthy recording time
      required for the estimation process due to the extremely low signal-to-noise
      ratio (SNR). To improve the detection rate of ASSRs, a new observer-based real
      time ASSR detector is derived as an alternate solution to the existing methods.
      The ASSR detector has a simple structure, and provides fast and reliable signal
      detection. Simulation and experimental recorded data were used to evaluate the
      performances of the proposed approach. Compared with the conventional methods,
      the proposed method requires shorter recording time which could be proven as a
      valuable hearing screening or diagnostic tool.

PMID- 21096338
TI  - Classification of cardiac arrhythmias using competitive networks.
AB  - Information generated by sensors that collect a patient's vital signals are
      continuous and unlimited data sequences. Traditionally, this information requires
      special equipment and programs to monitor them. These programs process and react
      to the continuous entry of data from different origins. Thus, the purpose of this
      study is to analyze the data produced by these biomedical devices, in this case
      the electrocardiogram (ECG). Processing uses a neural classifier, Kohonen
      competitive neural networks, detecting if the ECG shows any cardiac arrhythmia.
      In fact, it is possible to classify an ECG signal and thereby detect if it is
      exhibiting or not any alteration, according to normality.

PMID- 21096339
TI  - A single tri-axial accelerometer-based real-time personal life log system capable
      of activity classification and exercise information generation.
AB  - Recording a personal life log (PLL) of daily activities is an emerging technology
      for u-lifecare and e-health services. In this paper, we present an accelerometer
      based personal life log system capable of human activity classification and
      exercise information generation. In our system, we use a tri-axial accelerometer
      and a real-time activity recognition scheme in which a set of augmented features
      of accelerometer signals, processed with Linear Discriminant Analysis (LDA), is
      classified by our hierarchical artificial neural network classifier: in the lower
      level of the classifier, a state of an activity is recognized based on the
      statistical and spectral features; in the upper level, an activity is recognized
      with a set of augmented features including autoregressive (AR) coefficients,
      signal magnitude area (SMA), and tilt angles (TA). Upon the recognition of each
      activity, we further estimate exercise information such as energy expenditure
      based on Metabolic Equivalents (METS), step count, walking distance, walking
      speed, activity duration, etc. Our PLL system functions in real-time and all
      information generated from our system is archived in a daily-log database. By
      testing our system on seven different daily activities, we have obtained an
      average accuracy of 84.8% in activity recognition and generated their relative
      exercise information.

PMID- 21096340
TI  - Automatic identification of Chronic Obstructive Pulmonary Disease Based on forced
      oscillation measurements and artificial neural networks.
AB  - The purpose of this study is to develop an automatic classifier based on
      Artificial Neural Networks (ANNs) to help the diagnostic of Chronic Obstructive
      Pulmonary Disease (COPD) using forced oscillation measurements (FOT). The
      classifier inputs are the parameters provided by the FOT and the output is the
      indication if the parameters indicate COPD or not. The available dataset consists
      of 7 possible input features (FOT parameters) of 90 measurements made in 30
      volunteers. Two feature selection methods (the analysis of the linear correlation
      and forward search) were used in order to identify a reduced set of the most
      relevant parameters. Two different training strategies for the ANNs were used and
      the performance of resulting networks were evaluated by the determination of
      accuracy, sensitivity (Se), specificity (Sp) and AUC. The ANN classifiers
      presented high accuracy (Se > 0.9, Se > 0.9 and AUC > 0.9) both in the complete
      and the reduce sets of FOT parameters. This indicates that ANNs classifiers may
      contribute to easy the diagnostic of COPD using forced oscillation measurements.

PMID- 21096341
TI  - Affinity-Matrix representation of spike train activities in the early visual
      pathway.
AB  - The understanding of how neurons interact in the visual cortex and what types of
      neurons are responsable for each interaction are still open questions. In order
      to analyse such problem, the spiking activity of neurons in the central visual
      pathway of awake owls was analyzed with Principal Component Analysis (PCA) and
      clustering techniques. Further analysis using kernel representation revealed the
      existence of two large groups of neurons with distinguishable behavior.

PMID- 21096342
TI  - State classification of heart rate variability by an artificial neural network in
      frequency domain.
AB  - This paper examines the feasibility of accurate state classification of autonomic
      nervous activity (ANA) based on the power spectral pattern of the heart rate
      fluctuations (HRFs). Some attempts have been made to utilize artificial neural
      networks (ANNs) to classify HRFs for clinical diagnoses such as ischemic
      cardiomyopathy, arrhythmia or sleep apnea. To establish the firm bases for making
      such clinical diagnoses, it may be important to examine the classification
      accuracy for the data in physiologically well defined conditions by e.g.
      application of autonomic blocking agents. In this paper the three layered
      perceptron has been trained by the heart rate data in variety of ANS states
      yielded by the application of Atropine and Propranolol to 14 healthy male
      subjects. Six state (control, atropine and propranolol for each of the spine and
      upright posture) classification based on power spectrum showed average
      sensitivity of 67.2% and specificity 91.2%. Four state (control, atropine,
      propranolol and double block for either spine or upright posture) resulted in the
      average classification sensitivity of 75.7% and specificity 95.5%. The paper
      revealed that entropy bandwidth and indices originated from characteristic
      oscillations of blood pressure change improve the classification accuracy.

PMID- 21096343
TI  - An automatic detector of drowsiness based on spectral analysis and wavelet
      decomposition of EEG records.
AB  - An algorithm to detect automatically drowsiness episodes has been developed. It
      uses only one EEG channel to differentiate the stages of alertness and
      drowsiness. In this work the vectors features are building combining Power
      Spectral Density (PDS) and Wavelet Transform (WT). The feature extracted from the
      PSD of EEG signal are: Central frequency, the First Quartile Frequency, the
      Maximum Frequency, the Total Energy of the Spectrum, the Power of Theta and Alpha
      bands. In the Wavelet Domain, it was computed the number of Zero Crossing and the
      integrated from the scale 3, 4 and 5 of Daubechies 2 order WT. The classifying of
      epochs is being done with neural networks. The detection results obtained with
      this technique are 86.5 % for drowsiness stages and 81.7% for alertness segment.
      Those results show that the features extracted and the classifier are able to
      identify drowsiness EEG segments.

PMID- 21096344
TI  - Assessment of human instantaneous arterial diameter using B-mode ultrasound
      imaging and artificial neural networks: Determination of wall mechanical
      properties.
AB  - Wall artery viscoelastic properties (WAVP) are correlated with structural and
      functional state of the arterial system. An accurate estimation of these
      properties is achieved measuring wall instantaneous diameter and pressure
      signals. The aim of this work was to evaluate a new non invasive estimation
      method of the instantaneous arterial diameter (D), and consequently, WAVP. Ten
      common carotid arteries of hypertensive men were evaluated. D was calculated by
      using B-mode ultrasonic imaging and specialized software designed with Artificial
      Neural Networks. Instantaneous arterial pressure of all subjects was measured by
      piezoelectric tonometry. Arterial wall properties were evaluated using a linear
      autoregressive with exogenous input model. The new method, which determinates the
      arterial diameter, was compared respect to a specialized and previously validated
      method. Results showed no significant differences in all parameters derived of D
      (Bland & Altman test) and no differences in all the wall arterial mechanic
      indexes (p>0.05). For these reasons, the developed software based on Artificial
      Neural Networks was successful in determining the parameters associated with
      arterial diameters and it opens up the possibility of real time calculations of
      arterial wall mechanical properties because of its simplicity.

PMID- 21096345
TI  - Human gait classification after lower limb fracture using Artificial Neural
      Networks and principal component analysis.
AB  - Vertical ground reaction force (vGRF) has been commonly used in human gait
      analysis making possible the study of mechanical overloads in the locomotor
      system. This study aimed at applying the principal component (PC) analysis and
      two Artificial Neural Networks (ANN), multi-layer feed forward (FF) and self
      organized maps (SOM), for classifying and clustering gait patterns from normal
      subjects (CG) and patients with lower limb fractures (FG). The vGRF from a group
      of 51 subjects, including 38 in CG and 13 in FG were used for PC analysis and
      classification. It was also tested the classification of vGRF from five subjects
      in a treatment group (TG) that were submitted to a physiotherapeutic treatment.
      Better results were obtained using four PC as inputs of the ANN, with 96%
      accuracy, 100% specificity and 85% sensitivity using SOM, against 92% accuracy,
      100% specificity and 69% sensitivity for FF classification. After treatment,
      three of five subjects were classified as presenting normal vGRF.

PMID- 21096346
TI  - Optimization of MFCC parameters using Particle Swarm Optimization for diagnosis
      of infant hypothyroidism using Multi- Layer Perceptron.
AB  - This paper presents a new application of the Particle Swarm Optimization (PSO)
      algorithm to optimize Mel Frequency Cepstrum Coefficients (MFCC) parameters, in
      order to extract an optimal feature set for diagnosis of hypothyroidism in
      infants using Multi-Layer Perceptrons (MLP) neural network. MFCC features is
      influenced by the number of filter banks (f(b)) and the number of coefficients
      (n(c)) used. These parameters are critical in representation of the features as
      they affect the resolution and dimensionality of the features. In this paper, the
      PSO algorithm was used to optimize the values of f(b) and n(c). The MFCC features
      based on the PSO optimization were extracted from healthy and unhealthy infant
      cry signals and used to train MLP in the classification of hypothyroid infant
      cries. The results indicate that the PSO algorithm could determine the optimum
      combination of f(b) and n(c) that produce the best classification accuracy of the
      MLP.

PMID- 21096347
TI  - Bio-signal analysis system design with support vector machines based on cloud
      computing service architecture.
AB  - Today, many bio-signals such as Electroencephalography (EEG) are recorded in
      digital format. It is an emerging research area of analyzing these digital bio
      signals to extract useful health information in biomedical engineering. In this
      paper, a bio-signal analyzing cloud computing architecture, called BACCA, is
      proposed. The system has been designed with the purpose of seamless integration
      into the National Taiwan University Health Information System. Based on the
      concept of. NET Service Oriented Architecture, the system integrates
      heterogeneous platforms, protocols, as well as applications. In this system, we
      add modern analytic functions such as approximated entropy and adaptive support
      vector machine (SVM). It is shown that the overall accuracy of EEG bio-signal
      analysis has increased to nearly 98% for different data sets, including open
      source and clinical data sets.

PMID- 21096348
TI  - Radiation characterization of an intra-oral wireless device at multiple ISM
      bands: 433 MHZ, 915 MHZ, and 2.42 GHz.
AB  - Intra-oral wireless devices are becoming more popular for physiological
      monitoring of the mouth environment and tongue-operated assistive technologies,
      such as the internal Tongue Drive System (iTDS). Here we present the experimental
      measurements and simulations of radiation performance of three commercial
      wireless transmitters operating at 433 MHz, 915 MHz, and 2.42 GHz, in the
      industrial-scientific-medical band when they were placed inside human mouth. The
      measurement and simulation results showed similarities in the attenuation
      patterns of all tested devices and indicated that the maximum attenuation occurs
      on the back of the head. There were no significant difference of average
      attenuation pattern between 433 MHz and 915 MHz, while the attenuation of 2.42
      GHz was higher in simulations but not in the measurements.

PMID- 21096349
TI  - Objective evaluation of stress with the blind by the monitoring of autonomic
      nervous system activity.
AB  - Accessibility for the blind in an urban space must be studied under real
      conditions in their daily environment. A new approach for evaluating the impact
      of environmental conditions on blind pedestrians is the objective measure of
      stress by the monitoring of the autonomic nervous system (ANS) activity. Original
      techniques of data analysis and spatial representation are proposed for the
      detection of the ANS activity through the assessment of the electrodermal
      activity. Skin resistance was recorded with an EmoSense system on 10 blind
      subjects who followed a charted course independently. The course was 1065 meters
      long and consisted of various environmental conditions in an urban space. The
      spatial frequency of the non-specific skin resistance responses was used to
      provide a more relevant representation of geographic hotspots. Results of
      statistical analysis based on this new parameter are discussed to conclude on
      phenomena causing mental stress with the blind moving in an urban space.

PMID- 21096350
TI  - Glass-type wireless PPG measuring system.
AB  - This paper is about a glass-type wireless bio-signal transmitter that can monitor
      the user's health state in daily life. The device implemented in this study
      consists of the transmission part and the receiving part. The transmission part
      includes a photoplethysmography(PPG) sensor for detecting pulse wave signals,
      accelerometer for detecting kinetic signals, and a wireless controller for
      transmitting acquired bio-information. The receiving part is designed to check
      and process transmitted data through interoperation with a PC. In the
      experiments, we collected data during a sitting posture and repeated sit-to-stand
      motion in laboratory environment, and analyzed the data. As to accuracy, the
      correlation between the peak-to-peak intervals in the signals of the Biopac
      equipment and the developed device measured in a sitting posture was 97.5%, and
      that measured in sit-to-stand motion was 87%. In addition, when bio-signals were
      transmitted through wireless communication, the transmission was successful 100%
      without any error. When pulse wave signals and kinetic signals were obtained and
      compared, the results proved the accuracy and daily applicability of the
      developed device, and the glass-type wireless bio-signal transmission system is
      expected to be applicable to unobtrusive health monitoring for the user.

PMID- 21096351
TI  - Measuring the attenuation characteristics of biological tissues enabling for low
      power in vivo RF transmission.
AB  - In clinical routine there is a need of periodical recording of vital parameters
      in high risk groups, for example the intraocular pressure. A solution for this
      could be an intracorporeal sensor using a wireless radio frequency (RF)
      transmitter. Thereby the risk of an infection is reduced, because a percutaneous
      connection is not necessary. A limiting factor for some organs is the size of
      implants. For designing an energy efficient low power RF transmitter, the
      dielectric parameters of representative biological tissues have to be determined.
      In this article two methods of measurement are presented, the coaxial probe and
      transmission line method. With this information about the dielectric parameters a
      miniaturized RF transmitter was built for proofing tests on phantoms with equal
      properties like biological tissue.

PMID- 21096352
TI  - System-level design trade-offs for truly wearable wireless medical devices.
AB  - Power and current management in emerging wearable medical devices, intended to
      continuously monitor physiological signals, are crucial design issues. The
      overall size of the electronic part of these systems is generally going to be
      dominated by the size of the batteries. Unfortunately, the options of smaller
      batteries do not only come at the expense of a lower capacity and hence shorter
      operation time. It also significantly constrains the amount of available current
      that can be used by different electronic blocks, as well as their operating power
      supply voltage. This paper discusses all the typical power and current management
      system level issues in the design of a typical miniature wearable wireless
      medical device. The discussion is illustrated with experimental results obtained
      with two devices built using two of the currently most popular low power
      commercial transceivers in the market, the Texas Instruments (TI) CC2500 and the
      Nordic Semiconductor nRF24L01+. The numbers presented can be used as a more
      realistic guidance of the energy per bit required in a real system
      implementation, as opposed to the ideal figures normally quoted by the
      manufacturers. Furthermore the analysis in this paper can also be extrapolated to
      the design of future wireless monitoring wearable devices with further optimized
      radio transceivers.

PMID- 21096353
TI  - Clutter isolation and cardiac monitoring using harmonic doppler radar with
      heterodyne receiver and passive RF tags.
AB  - A harmonic radar employing the use of harmonic passive RF tags can be
      successfully used to isolate the human respiration from environmental clutter.
      This paper describes the successful use of heterodyne receiver architecture with
      Doppler radar to track the heart-rate of a human being using passive body-worn
      harmonic tags in presence of a controlled noise generator at distances up to 120
      cm. The heterodyne system results have been compared with those of a conventional
      Doppler radar for cardiopulmonary monitoring that fails to isolate the noise from
      heart-rate in presence of a noise source.

PMID- 21096354
TI  - Insole sensor system for real-time detection of biped slip.
AB  - The study of bipedal gait is important for two primary reasons: biomimetic
      robotics and human gait rehabilitation. Both fields have numerous models
      describing bipedal locomotion that require a no-slip interaction with the ground
      for accuracy. This paper presents a low cost wearable sensor system capable of
      identifying slip in real time, which could afford rehabilitative analysts
      important information on the nature of patient falls, and provide robot designers
      a feedback ability with which to implement an active traction control system. The
      system can functionally provide better than 90% detection rates when calibrated
      to an individual.

PMID- 21096355
TI  - Model-based optimal immunization for antibody production in birds.
AB  - A dynamic model of the immune response in poultry was developed in order to
      enhance antibody production. Efficient production of antibodies is very valuable
      for researchers and physicians since they are used for other molecules detection.
      Large amounts of poultry-based antibodies are found in birds' eggs. However,
      inoculation timetables are based on empirical data. A seven differential equation
      system represents cellular and molecular populations of the humoral immune
      response in poultry. Model parameters are presented and simulation results
      reflect the typical immune responses. Finally, a genetic algorithm was designed
      in order to optimize antibody production.

PMID- 21096356
TI  - Phenomenological modeling of cell-to-cell and beat-to-beat variability in
      isolated Guinea Pig ventricular myocytes.
AB  - Experimental action potential (AP) recordings in isolated ventricular myoctes
      display significant temporal beat-to-beat variability in morphology and duration.
      Furthermore, significant cell-to-cell differences in AP also exist even for
      isolated cells originating from the same region of the same heart. However,
      current mathematical models of ventricular AP fail to replicate the temporal and
      cell-to-cell variability in AP observed experimentally. In this study, we propose
      a novel mathematical framework for the development of phenomenological AP models
      capable of capturing cell-to-cell and temporal variabilty in cardiac APs. A novel
      stochastic phenomenological model of the AP is developed, based on the
      deterministic Bueno-Orovio/Fentonmodel. Experimental recordings of AP are fit to
      the model to produce AP models of individual cells from the apex and the base of
      the guinea-pig ventricles. Our results show that the phenomenological model is
      able to capture the considerable differences in AP recorded from isolated cells
      originating from the location. We demonstrate the closeness of fit to the
      available experimental data which may be achieved using a phenomenological model,
      and also demonstrate the ability of the stochastic form of the model to capture
      the observed beat-to-beat variablity in action potential duration.

PMID- 21096357
TI  - Stochastic modeling of the neuronal activity in the thalamus of Essential Tremor
      patient.
AB  - Several stochastic models, with various degrees of complexity, have been proposed
      to model the neuronal activity from different parts of the human brain. In this
      paper, we use an Ornstein-Uhlenbeck Process (OUP) to model the spike activity
      recorded from the thalamus of a patient suffering from Essential Tremor at the
      time of implantation of the electrodes for Deep Brain Stimulation. From the
      recorded data, which contains information about the spike times of a single
      neuron, we identify the model parameters of the OUP.We then use these parameters
      to numerically simulate the inter-spike interval distribution. We show that the
      OUP provides excellent fits to the data recorded both without any external
      stimulation as well as with stimulation. We finally compare the fits with other
      stochastic models commonly used and we show the superiority of the OUP model in
      general.

PMID- 21096358
TI  - A generic ionic model of cardiac action potentials.
AB  - A generic cardiac ionic model employing membrane currents based on two-gate
      Hodgkin-Huxley kinetics is presented. Its generic nature allows it to accurately
      reproduce action potential waveforms in heterogeneous cardiac tissue by
      optimizing parameters governing ion channel kinetics and magnitudes. The model
      allows a user-defined number of voltage and time-dependent ion currents to be
      incorporated, in order to reproduce and predict electrophysiological action
      potential waveforms from multiple recordings in individual cardiac myocytes.

PMID- 21096359
TI  - Simulation of late gadolinium enhancement cardiac magnetic resonance studies.
AB  - In this study we propose a pipeline for simulation of late gadolinium enhancement
      images. We used a modified version of the XCAT phantom to improve simulation
      realism. Modifications included the modeling of trabeculae and papillary muscles,
      and the increase of sublabels to resemble tissue intensity variability. Magnetic
      properties for each body tissue were sampled in three settings: from Gaussian
      distributions, combining Rayleigh-Gaussian distributions, and from Rayleigh
      distributions. Thirty-two simulated datasets were compared with 32 clinical
      datasets from infarcted patients. Histograms were obtained for five tissues:
      lung, pericardium, myocardium, blood and hyper-enhanced area. Real and simulated
      histograms were compared with the Chi-square dissimilarity metric (chi(2)) and
      Kullback-Leibler divergence (KL). The generated simulated images look similar to
      real images according to both metrics. Rayleigh and the Rayleigh-Gaussian models
      obtained comparable average results (respectively: chi(2)= 0.16 +/- 0.12 and 0.18
      +/- 0.11; KL=0.15 +/- 0.17 and 0.16 +/- 0.18).

PMID- 21096360
TI  - Airway and tissue loading in postinterrupter response of the respiratory system -
      an identification algorithm construction.
AB  - The paper offers an enhancement of the classical interrupter technique algorithm
      dedicated to respiratory mechanics measurements. Idea consists in exploitation of
      information contained in postocclusional transient states during indirect
      measurement of parameter characteristics by model identification. It needs the
      adequacy of an inverse analogue to general behavior of the real system and a
      reliable algorithm of parameter estimation. The second one was a subject of
      reported works, which finally showed the potential of the approach to separation
      of airway and tissue response in a case of short-term excitation by interrupter
      valve operation. Investigations were conducted in a regime of forward-inverse
      computer experiment.

PMID- 21096361
TI  - Parameter estimation method for improper fractional models and its application to
      molecular biological systems.
AB  - Derived from biochemical principles, molecular biological systems can be
      described by a group of differential equations. Generally these differential
      equations contain fractional functions plus polynomials (which we call improper
      fractional model) as reaction rates. As a result, molecular biological systems
      are nonlinear in both parameters and states. It is well known that it is
      challenging to estimate parameters nonlinear in a model. However, in fractional
      functions both the denominator and numerator are linear in the parameters while
      polynomials are also linear in parameters. Based on this observation, we develop
      an iterative linear least squares method for estimating parameters in biological
      systems modeled by improper fractional functions. The basic idea is to transfer
      optimizing a nonlinear least squares objective function into iteratively solving
      a sequence of linear least squares problems. The developed method is applied to
      the estimation of parameters in a metabolism system. The simulation results show
      the superior performance of the proposed method for estimating parameters in such
      molecular biological systems.

PMID- 21096362
TI  - MML toolkit and work flow overview: Creating temporo-spatial heart models from
      CellML.
AB  - The Modeling Markup Language (MML) framework is a conceptual paradigm to quickly
      develop and solve biological models utilizing the CellML specification. In this
      study, we present the open source toolkit developed for this project and a
      possible workflow to create different scales of cardiac tissue models from a
      range of CellML models. Models from the CellML repository and other sources were
      tested for interoperability against the MML framework. Furthermore, to
      demonstrate the ability of the MML framework to deploy different scales of
      geometry, a model of atrial electrical activation is also presented.

PMID- 21096363
TI  - Design of a framework for modeling, integration and simulation of physiological
      models.
AB  - Modeling and simulation of physiological processes deal with the challenges of
      multiscale models in which coupling is very high within and among scales.
      Information technology approaches together with related analytical and
      computational tools will help to deal with these challenges. Physiological Model
      Simulation, Integration and Modeling Framework, Phy-SIM, provides the modeling
      environment which will help to cultivate various approaches to deal with the
      inherent problem of multiscale modeling of physiological systems. In this paper,
      we present the modular design of Phy-SIM. The proposed layered design of Phy-SIM,
      separates structure from function in physiological processes advocating modular
      thinking in developing and integrating physiological models. Moreover, the
      ontology based architecture will improve the modeling process by the mechanisms
      to attach anatomical and physiological ontological information to the models. The
      ultimate aim of the proposed approaches is to enhance the physiological model
      development and integration processes by providing the tools and mechanisms in
      Phy-SIM.

PMID- 21096364
TI  - ART-ML - a novel XML format for the biological procedures modeling and the
      representation of blood flow simulation.
AB  - The paper proposes a novel Extensible Markup Language (XML) based format called
      ART-ML that aims at supporting the interoperability and the reuse of models of
      blood flow, mass transport and plaque formation, exported by ARTool. ARTool is a
      platform for the automatic processing of various image modalities of coronary and
      carotid arteries. The images and their content are fused to develop morphological
      models of the arteries in easy to handle 3D representations. The platform
      incorporates efficient algorithms which are able to perform blood flow
      simulation. In addition atherosclerotic plaque development is estimated taking
      into account morphological, flow and genetic factors. ART-ML provides a XML
      format that enables the representation and management of embedded models within
      the ARTool platform and the storage and interchange of well-defined information.
      This approach influences in the model creation, model exchange, model reuse and
      result evaluation.

PMID- 21096365
TI  - WebPK, a web-based tool for custom pharmacokinetic simulation.
AB  - Drug bioavailability is a major failing point of new pharmaceuticals i.e. drugs
      fail to reach their target or fail to stay there long enough for therapeutic
      effect. Compounding this issue, significant variability exists between patients
      and how they metabolize and distribute a drug. We present WebPK, a web-based tool
      for simulation of custom pharmacokinetic models. Model parameters can be entered
      manually or uploaded as a file. Simulation computations are performed on the
      server side, and thus require minimal client resources, which makes WebPK
      suitable for mobile devices. Time series biodistribution data are returned to the
      user in graphical and numerical form for quick interpretation or archiving.
      Results generated from WebPK are consistent with previously published
      pharmacokinetic models. This work is expected to provide physicians with access
      to easy simulation of patient pharmacokinetic profiles, which will allow for the
      prescription of more efficient and personalized drug regimens. URL:
      http://webpk.bme.gatech.edu.

PMID- 21096366
TI  - A global sensitivity tool for cardiac cell modeling: Application to ionic current
      balance and hypertrophic signaling.
AB  - Cardiovascular diseases are the major cause of death in the developed countries.
      Identifying key cellular processes involved in generation of the electrical
      signal and in regulation of signal transduction pathways is essential for
      unraveling the underlying mechanisms of heart rhythm behavior. Computational
      cardiac models provide important insights into cardiovascular function and
      disease. Sensitivity analysis presents a key tool for exploring the large
      parameter space of such models, in order to determine the key factors determining
      and controlling the underlying physiological processes. We developed a new global
      sensitivity analysis tool which implements the Morris method, a global
      sensitivity screening algorithm, onto a Nimrod platform, which is a distributed
      resources software toolkit. The newly developed tool has been validated using the
      model of IP3-calcineurin signal transduction pathway model which has 30
      parameters. The key driving factors of the IP3 transient behaviour have been
      calculated and confirmed to agree with previously published data. We next
      demonstrated the use of this method as an assessment tool for characterizing the
      structure of cardiac ionic models. In three latest human ventricular myocyte
      models, we examined the contribution of transmembrane currents to the shape of
      the electrical signal (i.e. on the action potential duration). The resulting
      profiles of the ionic current balance demonstrated the highly nonlinear nature of
      cardiac ionic models and identified key players in different models. Such
      profiling suggests new avenues for development of methodologies to predict drug
      action effects in cardiac cells.

PMID- 21096367
TI  - A simple yet effective data integration approach to tree-based microarray data
      classification.
AB  - Different biological labs conduct similar experiments on same diseases. It is
      highly desirable to have a better model based on more experimental results than
      that on a single result. In this paper, we propose a method for integrating
      microarray data from multiple sources for building classification models. To test
      the method, we use three real world microarray data sets from different labs with
      different experimental devices and environments. Although microarray data is well
      known for its inconsistencies across labs, we demonstrate that it is possible to
      build consistent models using data sets from multiple labs. We report our method,
      experimental results and observations in the paper.

PMID- 21096368
TI  - Effects of TMS coil geometry on stimulation specificity.
AB  - Transcranial magnetic stimulation has become an established tool in experimental
      cognitive neuroscience and has more recently been applied clinically. The current
      spatial extent of neural activation is several millimeters but with greater
      specificity, transcranial magnetic stimulation can potentially deliver real time
      feedback to reinforce or extinguish behavior by exciting or inhibiting localized
      neural circuits. The specificity of transcranial magnetic stimulation is a
      function of the stimulation coil geometry. In this paper, a practical multilayer
      framework for the design of miniaturized stimulation coils is presented. This
      framework is based on a magnet wire fabricated from 2500 braided ultrafine wires.
      Effects of coil bending angle on stimulation specificity are examined using
      realistic finite element method simulations. A novel stimulation coil with one
      degree of freedom is also proposed that shows improved specificity over the
      conventional fixed coils. This type of coil could be potentially used as a
      feedback system for a bidirectional brain machine interface.

PMID- 21096369
TI  - Functional regeneration of severed peripheral nerve using an implantable
      electrical stimulator.
AB  - This paper presents functional regeneration of severed peripheral nerve using a
      polymer-based implantable electrical stimulator. A polyimide based conduit
      electrode was made by micro-fabrication and a stimulation chip was designed to
      generate biphasic current pulse for electrical stimulation. The stimulation chip
      was packaged with a battery using silicone elastomer, and integrated with the
      electrode. The implantable electrical stimulator was implanted in the rat sciatic
      nerve with 7 mm gap. The electrical stimulation was applied for periods of one,
      two and four weeks between the proximal and the distal nerve stumps. After four
      weeks of post-operations, the degree of regeneration was evaluated through
      walking track assessments and by measuring neural response of the regenerated
      nerve. Based on these results, electrical stimulation, especially for two weeks
      of stimulation, could accelerate functional regeneration of the severed nerve.

PMID- 21096370
TI  - Modeling of microcavity electrodes for medical implants.
AB  - A common, limiting factor in neuroprosthesis design is the safe charge-carrying
      capacity of the metallic electrodes that deliver electrical stimuli to biological
      tissue. If exceeded, adverse effects can occur, including electrode dissolution
      and cell necrosis. A straightforward method of addressing charge-carrying
      capacity limitations is to increase the surface area of the stimulating
      electrodes. However, for planar electrode arrays, this approach typically
      requires a corresponding increase in the distance between electrodes which can be
      detrimental to the efficacy of the device, particularly in sensory applications
      such as visual or auditory prostheses where densely-packed electrodes may offer
      advantage. An alternative approach involves fabricating electrodes such that they
      have a three-dimensional structure and, thus allow electrode spacing to be
      maintained while increasing the surface area. Here we describe a mathematical
      model that assists in the exploration of cup-shaped, micro-cavity electrodes
      within an insulating substrate. This model simulates the electrical fields
      generated by these electrodes and is used to explore the relationship between the
      micro-cavity electrode depth and the electrical field generated within the
      electrolyte. For electrode diameters of 350 u, spaced at a pitch of 600 epsilonm,
      the model predicts that the most efficacious microcavity depth is 400 epsilonm.

PMID- 21096371
TI  - A high-voltage, high-current CMOS pulse generator ASIC for deep brain
      stimulation.
AB  - A high-voltage, high-current pulse generator ASIC based on 0.35-epsilonm high
      voltage CMOS technology is presented. The chip has eight independently-controlled
      biphasic output channels that can generate either current- or voltage-controlled
      pulses. The output driver is capable of delivering current up to 1.26 mA or 5.04
      mA and voltage up to 2.36 V or 9.45 V; all with 6-bit resolution. The stimulation
      frequency can be adjusted between 3 Hz to 5 kHz, while pulse width can vary from
      20 us to 640 epsilons in 20 epsilons steps for 100-kHz clock frequency. The
      timing parameters can be adjusted further by varying the clock frequency. These
      parameters, including pulse phase, can be programmed independently in each
      channel to allow different waveform generation. The foregoing provides an on-chip
      solution for an arbitrary function generator that can be monolithically
      fabricated with the rest of the circuitry. Based on its configuration this chip
      is an ideal solution for deep brain stimulation (DBS) electrode for targeted
      stimulation through current steering.

PMID- 21096372
TI  - Design and experiment of a neural signal detection using a FES driving system.
AB  - The channel bridging, signal regenerating, and functional rebuilding of injured
      nerves is one of the most important issues in life science research. In recent
      years, some progresses in the research area have been made in repairing injured
      nerves with microelectronic neural bridge. Based on the previous work, this paper
      presents a neural signal detection and functional electrical stimulation (FES)
      driving system with using high performance operational amplifiers, which has been
      realized. The experimental results show that the designed system meets
      requirements. In animal experiments, sciatic nerve signal detection, regeneration
      and function rebuilding between two toads have been accomplished successfully by
      using the designed system.

PMID- 21096373
TI  - Preliminary investigations on laminin coatings for flexible polyimide/platinum
      thin films for PNS applications.
AB  - The aim of this work was to investigate the possibility to obtain stable
      bioactive coatings for polyimide/platinum neural interfaces based on thin film
      technology for applications into the peripheral nervous system (PNS). Laminin
      (LI), a glycoprotein of the extracellular matrix, which guides and promotes
      differentiation and growth of neurons, was selected to deposit bioactive
      coatings. Dip-coating was performed on dummy structures at different LI
      concentrations. Indirect methods allowed to identify and characterize laminin on
      coated samples. Mechanical stability was also confirmed by indirect evaluations.
      Pilot experiments with differentiated PC12 cells, by the addition of nerve growth
      factor (NGF), showed improved neurite outgrowth on the coated probes compared to
      bare polyimide samples.

PMID- 21096374
TI  - Optimizing the diameter of holes for flexible regeneration microelectrode.
AB  - In this study, we suggest a new guideline for regeneration microelectrode to be
      implanted between the severed stumps of peripheral nerves, the microelectrode
      designed particularly for connecting the signal line of an artificial hand
      directly to the nerve system. The nerve regeneration microelectrode is an
      interface device expected to realize a BMI (brain-machine interface).

PMID- 21096375
TI  - Recognition and inhibition of dorsal horn nociceptive signals within a closed
      loop system.
AB  - We implemented an integrated system that can acquire neuronal signals from spinal
      cord dorsal horn neurons, wirelessly transmit the signals to a computer, and
      recognize the nociceptive signals from three different mechanical stimuli (brush,
      pressure and pinch). Positive peak detection method was chosen to distinguish
      between signal spikes. The inter spike intervals (ISIs) were calculated from the
      identified action potentials (APs) and fed into a numerical array called cluster.
      When the sum of the ISIs in the cluster reached a critical level, the program
      recognized the recorded signals as nociceptive inputs. The user has the
      flexibility to tune both the cluster size and critical threshold for individual's
      need to reach optimization in pain signal recognition. The program was integrated
      with a wireless neurostimulator to form a feedback loop to recognize and inhibit
      nociceptive signals.

PMID- 21096377
TI  - ODEs model of foreign body reaction around peripheral nerve implanted electrode.
AB  - The foreign body reaction that the neural tissue develops around an implanted
      electrode contributes to insulate the probe and enhances the electrical and
      mechanical mismatch. It is a complex interaction among cells and soluble
      mediators and the knowledge of this phenomenon can benefits of formal and
      analytical methods that characterize the mathematical models. This work offers a
      lumped component model, described by ordinary differential equations, that taking
      into account the main geometrical (size, shape, insertion angle) and chemical
      (coating surface) properties of the implant predict the thickness of the fibrotic
      capsule in a time frame when the reaction stabilizes. This tool allows to
      evaluate different hypothetical solutions for accounting the tissue-electrode
      mismatch.

PMID- 21096376
TI  - Restoring the basal ganglia in Parkinson's disease to normal via multi-input
      phase-shifted deep brain stimulation.
AB  - Deep brain stimulation (DBS) injects a high frequency current that effectively
      disables the diseased basal ganglia (BG) circuit in Parkinson's disease (PD)
      patients, leading to a reversal of motor symptoms. Though therapeutic, high
      frequency stimulation consumes significant power forcing frequent surgical
      battery replacements and causing widespread influence into other brain areas
      which may lead to adverse side effects. In this paper, we conducted a rigorous
      study to assess whether low frequency signals can restore behavior in PD patients
      by restoring neural activity in the BG to the normal state. We used a biophysical
      based model of BG nuclei and motor thalamus whose parameters can be set to
      simulate the normal state and the PD state with and without DBS. We administered
      pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies
      ranging from 1-150Hz. For each DBS frequency, we computed statistics on the
      simulated neural activity to assess whether it is restored to the normal state.
      In particular, we searched for DBS waveforms that suppress pathological bursting,
      oscillations, correlations and synchronization prevalent in the PD state and that
      enable thalamic cells to relay cortical inputs reliably. We found that none of
      the tested waveforms restores neural activity to the normal state. However, our
      simulations led us to construct a novel DBS strategy involving low frequency
      multi-input phaseshifted DBS to be administered into the STN. This strategy
      successfully suppressed all pathological symptoms in the BG in addition to
      enabling thalamic cells to relay cortical inputs reliably.

PMID- 21096378
TI  - Dual-monitor deterministic hardware for visual stimuli generation in neuroscience
      experiments.
AB  - This article describes the development of a dual-monitor visual stimulus
      generator that is used in neuroscience experiments with invertebrates such as
      flies. The experiment consists in the visualization of two fixed images that are
      displaced horizontally according to the stimulus data. The system was developed
      using off-the-shelf FPGA kits and it is capable of displaying 640x480 pixels with
      256 intensity levels at 200 frames per second (FPS) on each monitor. A Raster
      plot of the experiment with the superimposed stimuli was generated as the result
      of this work. A novel architecture was developed, using the same DOT Clock for
      both monitors, and its implementation generates a perfect synchronism in both
      devices.

PMID- 21096379
TI  - Remote tactile sensing glove-based system.
AB  - A complete glove-based master-slave tactile feedback system was developed to
      provide users with a remote sense of touch. The system features a force-sensing
      master glove with piezoresistive force sensors mounted at each finger tip, and a
      pressure-transmitting slave glove with silicone-based pneumatically controlled
      balloon actuators, mounted at each finger tip on another hand. A control system
      translates forces detected on the master glove, either worn by a user or mounted
      on a robotic hand, to discrete pressure levels at the fingers of another user.
      System tests demonstrated that users could accurately identify the correct finger
      and detect three simultaneous finger stimuli with 99.3% and 90.2% accuracy,
      respectively, when the subjects were located in separate rooms. The glove-based
      tactile feedback system may have application to virtual reality, rehabilitation,
      remote surgery, medical simulation, robotic assembly, and military robotics.

PMID- 21096380
TI  - A multi-channel low-power system-on-chip for single-unit recording and narrowband
      wireless transmission of neural signal.
AB  - This paper reports a multi-channel neural recording system-on-chip (SoC) with
      digital data compression and wireless telemetry. The circuit consists of a 16
      amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a
      digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK
      transmitter. Even though only 16 amplifiers are present in our current die
      version, the whole system is designed to work with 64 channels demonstrating the
      feasibility of a digital processing and narrowband wireless transmission of 64
      neural recording channels. A digital data compression, based on the detection of
      action potentials and storage of correspondent waveforms, allows the use of a
      1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low
      frequency deviation, Manchester-coded modulation are crucial for exploiting a
      narrowband wireless link and an efficient embeddable antenna. The chip is
      realized in a 0.35- epsilonm CMOS process with a power consumption of 105
      epsilonW per channel (269 epsilonW per channel with an extended transmission
      range of 4 m) and an area of 3.1 * 2.7 mm(2). The transmitted signal is captured
      by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and
      then sent to a PC via an FPGA module. The system has been tested for electrical
      specifications and its functionality verified in in-vivo neural recording
      experiments.

PMID- 21096381
TI  - A high-speed circuit architecture for IR-UWB transmission of fast-scan cyclic
      voltammetry in 0.35 epsilonm CMOS.
AB  - This paper reports on the design of a high-speed circuit for impulse radio ultra
      wideband (IR-UWB) transmission of 16-channel neurochemical activity recorded
      using 300-V/s fast-scan cyclic voltammetry (FSCV). Simulated in a low-cost 0.35
      epsilonm standard complementary metal-oxide-semiconductor (CMOS) technology, the
      circuit generates 3(rd)-derivative Gaussian pulses with sub-nanosecond duration,
      which are highpass filtered externally using a 4(th)-order Butterworth filter
      before feeding to an off-chip UWB antenna. The power spectral density (PSD)
      achieves a peak emission frequency of 4.6 GHz with a 2.3-GHz bandwidth (-10 dB),
      and is fully compliant with the UWB emission mask. The energy efficiency in pulse
      generation is 161.7 pJ/pulse that leads to a power consumption of 4.85 mW from
      3.3 V for a data rate of 15 Mbps, when two pulses are used to transmit a single
      data bit.

PMID- 21096382
TI  - Wireless channel characterization for mm-size neural implants.
AB  - This paper discusses an approach to modeling and characterizing wireless channel
      properties for mm-size neural implants. Full-wave electromagnetic simulation was
      employed to model signal propagation characteristics in biological materials.
      Animal tests were carried out, proving the validity of the simulation model over
      a wide range of frequency from 100MHz to 6GHz. Finally, effects of variability
      and uncertainty in human anatomy and dielectric properties of tissues on these
      radio links are explored.

PMID- 21096383
TI  - An implantable VLSI architecture for real time spike sorting in cortically
      controlled Brain Machine Interfaces.
AB  - Brain Machine Interface (BMI) systems demand real-time spike sorting to
      instantaneously decode the spike trains of simultaneously recorded cortical
      neurons. Real-time spike sorting, however, requires extensive computational power
      that is not feasible to implement in implantable BMI architectures, thereby
      requiring transmission of high-bandwidth raw neural data to an external computer.
      In this work, we describe a miniaturized, low power, programmable hardware module
      capable of performing this task within the resource constraints of an implantable
      chip. The module computes a sparse representation of the spike waveforms followed
      by "smart" thresholding. This cascade restricts the sparse representation to a
      subset of projections that preserve the discriminative features of neuron
      specific spike waveforms. In addition, it further reduces telemetry bandwidth
      making it feasible to wirelessly transmit only the important biological
      information to the outside world, thereby improving the efficiency, practicality
      and viability of BMI systems in clinical applications.

PMID- 21096384
TI  - A low-power self-biased neural amplifier for implantable EEG recording system
      ICs.
AB  - This paper presents a low-power and self-biased neural amplifier for implantable
      EEG recording system ICs with a high-density interface. To achieve low-power
      consumption, small die-area, high gain, and high CMRR, a fully differential
      Chappell OTA is employed along with a capacitive feedback loop. The amplifier
      operating at +/- 1.2V has a gain of 65.6dB and consumes a power of 1.7 microW.
      The bandwidth extends from a low-frequency cutoff of below 1 Hz to a high
      frequency cutoff of 300Hz which is suitable for EEG signals. This proposed
      amplifier has an input-referred noise of 9.76 mmicroV(RMS) and THD of 1.86% with
      respect to 1mV(PP) input at 100Hz. This low-power self-biased neural amplifier
      occupies an active die-area of 0.244 mm(2) and is under fabrication in 0.35
      microm CMOS 4M2P Process.

PMID- 21096385
TI  - A device for vacuum drying, inert gas backfilling and solder sealing of hermetic
      implant packages.
AB  - Modern implanted devices utilize microelectronics that have to be protected from
      the body fluids in order to maintain their functionality over decades. Moisture
      protection of implants is addressed by enclosing the electronic circuits into gas
      tight packages. In this paper we describe a device that allows custom-built
      hermetic implant packages to be vacuum-dried (removing residual moisture from
      inside the package), backfilled with an inert gas at adjustable pressure and
      hermetically sealed employing a solder seal. A typical operation procedure of the
      device is presented.

PMID- 21096386
TI  - A high-performance transcutaneous battery charger for medical implants.
AB  - As new functionality is added to the implantable devices, their power
      requirements also increase. Such power requirements make it hard for keeping such
      implants operational for long periods by non-rechargeable batteries. This result
      in a need for frequent surgeries to replace these batteries. Rechargeable
      batteries can satisfy the long-term power requirements of these new functions. To
      minimize the discomfort to the patients, the recharging of the batteries should
      be as infrequent as possible. Traditional battery charging methods have low
      battery charging efficiency. This means they may limit the amount of charge that
      can be delivered to the device, speeding up the depletion of the battery and
      forcing frequent recharging. In this paper, we evaluate the suitability of a
      state-of-the-art general purpose charging method called current-pumped battery
      charger (CPBC) for implant applications. Using off-the-shelf components and with
      minimum optimization, we prototyped a proof-of-concept transcutaenous battery
      charger based on CPBC and show that the CPBC can charge a 100 mAh battery
      transcutaneously within 137 minutes with at most 2.1 degrees C increase in tissue
      temperature even with a misalignment of 1.3 cm in between the coils, while
      keeping the battery charging efficiency at 85%.

PMID- 21096387
TI  - Fabrication and test of a hermetic miniature implant package with 360 electrical
      feedthroughs.
AB  - A fabrication technology for small hermetic implant packages with large numbers
      of electrical feedthroughs is presented. First prototypes were fabricated on a
      ceramic substrate of 25.25 mm area, having a metal cup of 5 mm height soldered to
      it. These prototypes provide 360 feedthroughs. The electrical properties of the
      feedthroughs are characterized and the leakage rate of the packages is determined
      using helium fine leak tests. The amount of water sealed inside the packages is
      investigated. Based on maximum allowable water vapour concentrations inside
      hermetic packages reported in literature and applying a commonly accepted
      mathematical model, we predicted a minimum lifetime to water-induced failure of a
      few hundred years.

PMID- 21096388
TI  - Dynamic assessment of spontaneous baroreflex sensitivity by means of time
      frequency analysis using either RR or pulse interval variability.
AB  - In this study we propose a method to continuously assess the changes of
      spontaneous baroreflex sensitivity (BRS). Systolic arterial pressure and RR
      intervals are analyzed by time-frequency analysis to estimate their instantaneous
      powers as well as the time-course of their spectral coherence. The BRS estimated
      in classical frequency bands is compared to the BRS estimated in dynamic
      frequency bands centered on respiratory frequency. The possibility of obtaining
      reliable estimations of the BRS using the pulse interval from the pressure signal
      as a surrogate of the RR is considered. Results on a tilt table test database
      suggest that is possible to obtain reliable BRS estimates just from the analysis
      of the pressure signal, without the need of ECG recordings.

PMID- 21096389
TI  - Analysis of heart rate variability dynamics during propofol and dexmedetomidine
      anesthesia.
AB  - It has been observed that heart rate variability (HRV) diminishes during
      anesthesia, but the exact mechanisms causing it are not completely understood.
      The aim of this paper was to study the dynamics of HRV during low dose propofol
      (N=9) and dexmedetomidine (N=8) anesthesia by using state-of-the-art time-varying
      methods, and thereby ultimately try to improve the safety of anesthesia. The time
      varying spectrum is estimated by using a Kalman smoother approach. The results
      show that there is an overall increase in HRV and decrease in heart rate prior to
      loss of consciousness. For dexmedetomidine these changes are more considerable
      than for propofol. For dexmedetomidine the variability also seems to start
      decreasing right after loss of consciousness, whereas for propofol HRV continues
      increasing.

PMID- 21096390
TI  - Multichannel surface electromyography classification based on muscular synergy.
AB  - With the aim to control a multiple degrees of freedom electromechanical devices,
      e.g., assistive robots, powered wheelchair, etc., this paper proposes a real-time
      multichannel surface electromyography classification scheme based on the
      coordination or synergies between a functional group of muscles: biceps brachii,
      triceps brachii, pronator teres, and brachioradialis. The muscular synergy is
      evaluated by the analysis of a multivariate function, composed by the four
      corresponding neuromuscular activation functions, and the cross-correlation
      matrix of muscular force estimated through the root mean square (RMS) value of
      sEMG amplitude. The resulting features from the training set were used to train
      an artificial neural network with classification accuracy up of 90%.

PMID- 21096391
TI  - Multiple Coherence vs Multiple Component Synchrony Measure for somatosensory
      evoked response detection.
AB  - This work aims at comparing the performance of two Multivariate Objective
      Response Detection (MORD) techniques in the frequency domain, the Multiple
      Coherence (MC) and the Multiple Component Synchrony Measure (MCSM), for tibial
      nerve somatosensory evoked potential (SEP) detection. Electroencephalographic
      (EEG) signals during somatosensory stimulation were collected from forty adult
      volunteers using the 10-20 International System. The stimulation was carried out
      throughout current pulses (200 us width) applied to the right posterior tibial
      nerve (motor threshold intensity level) at the rate of 5 Hz. The response
      detection was based on rejecting the null hypothesis of response absence (M = 100
      and M = 800 epochs and significance level alpha = 0.05). The MORD techniques were
      applied to the pairs of derivations [Cz][Fz] and [C3][C4]. The MC outperforms the
      MCSM, regardless the pair of derivations or the number of epochs used for the
      estimates calculation. Hence, the MC should be used, if two derivations are
      available for SEP recording.

PMID- 21096392
TI  - Analysis of propagation of multi-channel EEG in the test of sustained attention.
AB  - the psychological construct 'sustained attention' describes a basic component of
      attention characterized by the subject's readiness to detect rarely and
      unpredictably occurring signals over prolonged periods of time. In this study,
      six healthy volunteers underwent a sustained attention to response task (SART),
      while their electroencephalographic (EEG) were recorded contemporarily. Directed
      Transfer Function (DTF) was used as estimator for direction of propagation of EEG
      function coupling. The results of DTF showed that the information flux within EEG
      functional coupling changed when attention condition changed from inattention
      state to sustained attention state, principally at alpha and beta rhythms. The
      DTF could be used to evaluate sustained attention condition and they might be
      used for research on damage of attention mechanisms of ADHD and TBI diseases in
      future.

PMID- 21096393
TI  - Decoder remapping to counteract neuron loss in brain-machine interfaces.
AB  - Variability of single-unit neural recordings can significantly affect the overall
      performance achieved by brain machine interfaces (BMI). In this paper, we present
      a novel technique to adapt a linear filter commonly used in BMI to compensate for
      loss of neurons from the recorded neural ensemble, thus minimizing loss in
      performance. We simulate the gains achieved by this technique using a model of
      the learning process during closed-loop BMI operation. This simulation suggests
      that we can adapt to the loss of 24% of the neurons controlling a BMI with only
      13% drop in performance.

PMID- 21096394
TI  - Altering function in cortical networks by short-latency, paired stimulation.
AB  - Plasticity is a crucial component of normal brain function and a critical
      mechanism for recovery from injury. Numerous experimental studies have attempted
      to elucidate its underlying mechanisms under both in vitro and in vivo
      conditions. Short latency, associative pairing of presynaptic "trigger" spiking
      with stimulus-induced postsynaptic depolarization of a target neuron has been
      shown to lead to changes in the effectiveness of a stimulus applied to the
      presynaptic neuron. We have used similar methods to demonstrate changes in the
      statistically inferred functional connections among small groups of recorded
      neurons in rat sensorimotor cortex. These induced changes transcended simple
      changes in stimulus-evoked activity. Rather, they reflected a robust
      reorganization of network connectivity revealed by changes in the patterns of
      spikes in the cells' spontaneous discharge. We hypothesized that by strengthening
      the functional connections from trigger to target neurons, we might demonstrate a
      related behavioral change. To test this hypothesis, we trained rats to respond to
      a near-threshold, intracortical stimulus cue. Following 1-2 days of paired, short
      latency stimulation, the sensitivity of these rats to the cue was increased. The
      latency dependence and the timecourse of this effect were very similar to the
      corresponding parameters of the inferred connectivity changes in the first
      experiment. Such targeted connectivity changes may provide a tool for rerouting
      the flow of information through a cortical network, with profound implications
      for both rehabilitation and brain-machine interface applications.

PMID- 21096395
TI  - Finite element and biophysics modelling of intraneural transversal electrodes:
      Influence of active site shape.
AB  - Neural interfaces are aimed at creating an intimate contact with neural cells,
      either to stimulate the nerves or to record neural signals. This would allow the
      development of neurocontrolled artificial devices. The quality of these systems
      can be improved by increasing the selectivity of the neural interfaces used to
      stimulate or to record the activity of specific subsets of cells. Hence
      selectivity is of major importance for successful applications. The selectivity
      of these devices is a key issue and could be strongly influenced by the design of
      the microelectrode used. In this paper, a novel integrated FEM/Biophysical model
      based on anatomical and immunochemistry data providing guidelines for the design
      of more effective intraneural electrodes is used in studying the influence of
      active site shapes on the quality of stimulation and some preliminary results are
      also shown.

PMID- 21096396
TI  - Extracting an evaluative feedback from the brain for adaptation of motor
      neuroprosthetic decoders.
AB  - The design of Brain-Machine Interface (BMI) neural decoders that have robust
      performance in changing environments encountered in daily life activity is a
      challenging problem. One solution to this problem is the design of neural
      decoders that are able to assist and adapt to the user by participating in their
      perception-action-reward cycle (PARC). Using inspiration both from artificial
      intelligence and neurobiology reinforcement learning theories, we have designed a
      novel decoding architecture that enables a symbiotic relationship between the
      user and an Intelligent Assistant (IA). By tapping into the motor and reward
      centers in the brain, the IA adapts the process of decoding neural motor commands
      into prosthetic actions based on the user's goals. The focus of this paper is on
      extraction of goal information directly from the brain and making it accessible
      to the IA as an evaluative feedback for adaptation. We have recorded the neural
      activity of the Nucleus Accumbens in behaving rats during a reaching task. The
      peri-event time histograms demonstrate a rich representation of the reward
      prediction in this subcortical structure that can be modeled on a single trial
      basis as a scalar evaluative feedback with high precision.

PMID- 21096397
TI  - Comparison of force and power generation patterns and their predictions under
      different external dynamic environments.
AB  - Use of neural activity to predict kinematic variables such as position, velocity
      and direction etc of movements has been implemented in real-time control of
      robotic systems and computer cursors. In everyday life, however, we generate
      variable amounts of force to manipulate objects of different inertial properties
      or to follow the same trajectory under different external dynamic environments
      like air or water. The resultant work during such movements, and its time
      derivative power, should depend on the dynamics of the movement. In order to give
      the users of a brain-machine interface (BMI) comprehensive control of a
      prosthetic limb under different dynamic conditions, it is imperative to consider
      the dynamics-related parameters like end-effector forces, joint torques or power.
      In this paper, we show distribution patterns of two such dynamics parameters -
      force and power - and their predictive efficiency under different dynamic
      environmental conditions. We intend to find the force-related parameter, which
      has optimal predictive efficiency across different dynamic environments that is
      generalization. Our ultimate goal is to materialize a force-based brain-machine
      interface (fBMI).

PMID- 21096398
TI  - Reconfigurable embedded system architecture for next-generation Neural Signal
      Processing.
AB  - This work presents a new architectural framework for next generation Neural
      Signal Processing (NSP). The essential features of the NSP hardware platform
      include scalability, reconfigurability, real-time processing ability and data
      storage. This proposed framework has been implemented in a proof-of-concept NSP
      prototype using an embedded system architecture synthesized in a
      Xilinx((r))Virtex((r))5 development board. The prototype includes a threshold
      based spike detector and a fuzzy logic-based spike sorter.

PMID- 21096399
TI  - Altered interactions of heart rate and blood pressure during normal and abnormal
      pregnancy.
AB  - The assessment of the autonomic cardiovascular regulation provides important
      diagnostic and prognostic information. The aim of this study was to investigate
      the alterations of this autonomic regulation in the progress of a normal
      pregnancy and in several pregnancy disorders associated with hypertension,
      especially pre-eclampsia, applying the method of Joint Symbolic Dynamics (JSD).
      The JSD reveals nonlinear interactions/ coupling between two time series.

PMID- 21096400
TI  - An identifiable model to assess frequency-domain granger causality in the
      presence of significant instantaneous interactions.
AB  - We present a new approach for the investigation of Granger causality in the
      frequency domain by means of the partial directed coherence (PDC). The approach
      is based on the utilization of an extended multivariate autoregressive (MVAR)
      model, including instantaneous effects in addition to the lagged effects
      traditionally studied, to fit the observed multiple time series prior to PDC
      computation. Model identification is performed combining standard MVAR
      coefficient estimation with a recent technique for instantaneous causal modeling
      based on independent component analysis. The approach is first validated on
      simulated MVAR processes showing that, in the presence of instantaneous effects,
      only the extended model is able to interpret the imposed Granger causality
      patterns, while the traditional MVAR approach may yield strongly biased PDC
      estimates. The subsequent application to multichannel EEG time series confirms
      the potentiality of the approach in real data applications, as the importance of
      instantaneous effects led to significant differences in the PDC estimated after
      traditional and extended MVAR identification.

PMID- 21096401
TI  - The sequence technique revised: additional concepts on the assessment of
      spontaneous baroreflex function.
AB  - The sequence technique is commonly employed to estimate the baroreflex
      sensitivity from the analysis of systolic blood pressure (SBP) and RR Interval
      (RRI) recordings. Traditionally, the RRI+/SBP- and RRI-/SBP+ sequences are
      excluded from this analysis.

PMID- 21096402
TI  - Time-variant analysis of linear and non-linear phase couplings of and between
      frequency components of EEG burst patterns in full-term newborns.
AB  - Time-variant (tv) phase-locking and synchronization characteristics of and
      between low-frequency (<= 1.5 Hz) and high-frequency EEG oscillations (>= 3.5 Hz)
      of the trace alternant (TA) pattern in full-term newborns have been quantified to
      explore the origin of quadratic phase coupling (QPC, as non-linear phase coupling
      measure) between the frequency ranges 1 - 1.5 Hz <=> 3.5 - 4.5 Hz, which
      characterize the specific interactions of oscillations during the TA's burst
      activity. Using the Gabor transformation two measures of linear phase coupling,
      the phase-locking index (PLI) and the n:m phase synchronization index (PSI) have
      been determined. Phase-locking within the frequency ranges 1 -1.5 Hz and 3.5 -
      4.5 Hz, and synchronization between both frequency ranges exists. These phase
      characteristics are significant 2 sec after burst onset and are associated with
      the maximum-values of the QPC(1 - 1.5 Hz <=> 3.5 - 4.5 Hz) which demonstrates
      that a specific neuronal coordination between the dynamics of phases and of
      amplitude-frequency dependencies must be underlying.

PMID- 21096403
TI  - Measures of connectivity among the different brain areas during an attention
      task.
AB  - The functional connectivity of the brain is investigated through the study of
      multivariate autoregressive models (MVAR) applied to multichannel EEG recordings.
      After the identification of the model, different indices can be calculated that
      are able to quantify direct and indirect functional connections between cortical
      areas. These methodology is used for the investigation of possible connectivity
      alterations in patients after Traumatic Brain Injury (TBI) who suffered from
      Diffuse Assonal Injury (DAI). As one of main consequences of DAI are cognitive
      and attention impairment, the subjects underwent an attention test (Conners CPT)
      during EEG recording. In order to avoid spurious coherences, related to the
      volume effect of the head, a Laplacian transformation was applied to the data
      before connectivity evaluation. The MVAR was fitted to the different phases of
      the test and different indices were calculated. Even if the general connectivity
      is not different between patients and controls, differences were found in inter
      hemispheric connectivity. Both in beta and in gamma bands central electrodes C3
      and C4 seem the main sources of activity that is directed mainly towards Fp1 and
      Fp2. Such connectivity is less intense in DAI subjects.

PMID- 21096404
TI  - Coherence and imaginary part of coherency identifies cortico-muscular and cortico
      thalamic coupling.
AB  - The understanding of the interaction between muscle control and cortical areas
      and between subcortical and cortical areas is important for the effective
      treatment of patients with movement disorders. The combination of coherence (COH)
      and the imaginary part of coherency (iCOH) is applied here to
      electrophysiological data from patients with a movement disorder and to data from
      healthy subjects performing finger movements. The COH and iCOH between
      magnetoencephalographic (MEG) and electromyographic (EMG) signals of the healthy
      subjects yields the expected result for cortico-muscular coupling. Based on this
      the COH and iCOH between sub-thalamic nucleus local field potentials (STN-LFP)
      and MEG signals are assessed for deep brain stimulation patients with
      externalized LFP electrodes. The results suggest interactions in the 10 to 20 Hz
      range. Artificially mimicking volume conduction by re-referencing the STN
      electrodes to a surface EEG electrode leads to large changes in the COH and iCOH.
      This suggests that volume conduction is not important for the analysis of
      interactions between MEG and bipolar STN electrodes.

PMID- 21096405
TI  - Asymptotic behavior of generalized partial directed coherence.
AB  - This paper examines the asymptotic behavior of a newly defined general form of
      partial directed coherence. Both confidence interval and null hypothesis testing
      results are presented and illustrated.

PMID- 21096406
TI  - Information processing in brain and dynamic patterns of transmission during
      working memory task by the SDTF function.
AB  - We studied the dynamical pattern of transmission involved in the information
      processing during cognitive experiments engaging working memory. The ensemble
      averaging approach was used to fit a multichannel autoregressive model to the EEG
      signals recorded during the transitive reasoning task. The short-time directed
      transfer function was estimated for finding dynamical patterns of functional
      connectivity during the memory and reasoning task. The results indicated that
      there exist particular areas where information is processed as envisaged by
      transmissions between closely located electrodes. In case of reasoning task these
      local circuits were located in frontal and parietal regions. These areas (these
      local circuits) from time to time exchange information between each other..

PMID- 21096407
TI  - Frequency domain connectivity: an information theoretic perspective.
AB  - This paper addresses the relationship between Partial Directed Coherence (PDC)
      and Directed Transfer Function (DTF), popular multivariate connectivity measures
      employed in neuroscience, and information flow as quantified by mutual
      information rate.

PMID- 21096408
TI  - Functional connectivity networks in the autistic and healthy brain assessed using
      Granger causality.
AB  - In this study, we analyze brain connectivity based on Granger causality computed
      from magnetoencephalographic (MEG) activity obtained at the resting state in
      eight autistic and eight normal subjects along with measures of network
      connectivity derived from graph theory in an attempt to understand how
      communication in a human brain network is affected by autism. A connectivity
      matrix was computed for each subject individually and then group templates were
      estimated by averaging all matrices in each group. Furthermore, we performed
      classification of the subjects using support vector machines and Fisher's
      criterion to rank the features and identify the best subset for maximum
      separation of the groups. Our results show that a combined model based on
      connectivity matrices and graph theory measures can provide 87.5% accuracy in
      separating the two groups. These findings suggest that analysis of functional
      connectivity patterns may provide a valuable method for the early detection of
      autism.

PMID- 21096409
TI  - Imaging the social brain: multi-subjects EEG recordings during the "Chicken's
      game".
AB  - In this study we measured simultaneously by EEG hyperscannings the neuroelectric
      activity in 6 couples of subjects during the performance of the "Chicken's game",
      derived from game theory. The simultaneous recording of the EEG in couples of
      interacting subjects allows to observe and model directly the neural signature of
      human interactions in order to understand the cerebral processes generating and
      generated by social cooperation or competition. Results suggested that the one of
      the most consistently activated structure in this particular social interaction
      paradigm is the left orbitofrontal cortex. Connectivity results also showed a
      significant involvement of the orbitofrontal regions of both hemispheres across
      the observed population. Taken together, results confirms that the study of the
      brain activities in humans during social interactions can take benefit from the
      simultaneous acquisition of brain activity during such interaction.

PMID- 21096410
TI  - Large-scale cortical networks estimated from scalp EEG signals during performance
      of goal-directed motor tasks.
AB  - The evaluation of the topological properties of brain networks is an emergent
      research topic, since the estimated cerebral connectivity patterns often have
      relatively large size and complex structure. Since a graph is a mathematical
      representation of a network, the use of a theoretical graph approach would
      describe concisely the topological features of the functional brain connectivity
      network estimated using neuroimaging techniques. In the present study, we analyze
      the changes in brain synchronization networks using high-resolution EEG signals
      obtained during performance of a complex goal-directed visuomotor task. Our
      results show that the cortical network is more stable when subjects reach the
      goal than when they fail by hitting an obstacle. These findings suggest the
      presence of a possible cerebral "marker" for motor actions that result in
      successful reaching of a target.

PMID- 21096411
TI  - Technology enabled assessment and intervention protocols in a community and home
      care setting for independent living.
AB  - The graying of the population and uncontrolled healthcare costs are posing a
      great challenge for science and society. Movement of the focus of healthcare out
      of the acute high cost hospital setting is required in order to meet this
      challenge. This can be achieved through development of new models of healthcare
      that are based on early assessment and intervention and in the community.
      Judicious use of technology can underpin these new models of care to drive a more
      efficient healthcare system that enables older people live independently for
      longer in their own homes with a better quality of life. In this paper we
      describe the aims and outputs of an ageing research centre that brings industry
      and academic partners together in order to develop technology enabled assessment
      and intervention protocols for future models of care.

PMID- 21096412
TI  - Just enough measurement: a proposed paradigm for designing medical
      instrumentation.
AB  - Our research group hypothesizes that one way to provide low-cost healthcare
      delivery efficiently is through the use of a large number of inexpensive sensors
      that can provide meaningful medical data. Typical development of medical
      instrumentation pursues increased resolution and higher accuracy - accompanied by
      a corresponding increase in cost; it is no secret that high costs impose a heavy
      burden on healthcare. We seek to invert the adage that quality is more important
      than quantity by extracting high quality biomedical information from a large
      quantity of low-cost measurements, and to demonstrate this using measurement
      instrumentation developed in our lab for extra-clinical assessment and
      rehabilitation tools. This will be discussed in terms of our initial experiments
      in evaluating balance and postural stability. This is an area of critical
      clinical importance: 2.6 million non-fatal fall injuries in persons over age 65
      resulted in direct health care costs of $19 billion (in 2000) in the U.S., and
      the number of persons over age 65 in the U.S. is projected to more than double
      between 2000 and 2030.

PMID- 21096413
TI  - Upper extremity rehabilitation of children with cerebral palsy using
      accelerometer feedback on a multitouch display.
AB  - Cerebral palsy is a non-progressive neurological disorder caused by disturbances
      to the developing brain. Physical and occupational therapy, if started at a young
      age, can help minimizing complications such as joint contractures, and can
      improve limb range of motion and coordination. While current forms of therapy for
      children with cerebral palsy are effective in minimizing symptoms, many children
      find them boring or repetitive. We have designed a system for use in upper
      extremity rehabilitation sessions, making use of a multitouch display. The system
      allows children to be engaged in interactive gaming scenarios, while intensively
      performing desired exercises. It supports games which require completion of
      specific stretching or coordination exercises using one or both hands, as well as
      games which use physical, or "tangible" input mechanisms. To encourage correct
      posture during therapeutic exercises, we use a wireless kinematic sensor, worn on
      the patient's trunk, as a feedback channel for the games. The system went through
      several phases of design, incorporating input from observations of therapy and
      clinical sessions, as well as feedback from medical professionals. This paper
      describes the hardware platform, presents the design objectives derived from our
      iterative design phases and meetings with clinical personnel, discusses our
      current game designs and identifies areas of future work.

PMID- 21096414
TI  - Health informatics for low-cost and high-quality health care.
AB  - P-Health, a future health model that can be described as a 6-P's paradigm, aims
      to provide low cost and high quality health care via redesigning care practice
      and networking information systems at different levels. To realise p-Health, a
      multi-level health information system has to be developed for the processing,
      storage, transmission, acquisition and retrieval (P-STAR) of health information
      that spans multiple temporal and spatial scales and consists of multi-modality.
      This paper uses wearable devices, which have to be miniaturised, integrated,
      networked, digitalised, smart and standardised (MINDSS), as examples to
      illustrate how two or more P-STAR technologies are integrated together to
      implement a specific health care application under p-Health. In particular,
      standardisation of MINDSS devices that required a new measurement principle, such
      as the calibration procedure of cuff-less blood pressure measurement devices, is
      discussed.

PMID- 21096415
TI  - Digital divide: Use of electronic personal health record by different population
      groups.
AB  - Personal Health Record (PHR) has been increasingly recognized and actively
      promoted by the federal government, experts and industry as an important tool for
      improving healthcare in the U.S. However, the PHR use by patients and its utility
      have not been studied well. We have evaluated a web-based PHR in multiple
      locations covering diverse population groups. The study sites included a surgical
      specialty clinic, a medical specialty clinic, and a mental health clinic at the
      University of Washington, and a low-income elderly housing facility near Seattle
      in the state of Washington. The PHR use by the low-income elderly was limited due
      to poor technical skills and low physical/cognitive abilities. On the other hand,
      the younger and affluent populations used the web-based PHR much easily and
      efficiently compared to the older and low-income group. They regarded managing
      personal health information easy while the older group struggled. As more
      computer literate individuals age, the next-generation elderly are certain to be
      more technically skilled than the current generation. Although the reduced
      physical/cognitive abilities due to aging would still be a challenge, more
      elderly people will be able to not only use a PHR system but also use it to the
      full extent to get the maximum benefit.

PMID- 21096416
TI  - Wearable sensors: opportunities and challenges for low-cost health care.
AB  - Wearable sensors enable long-term continuous physiological monitoring, which is
      important for the treatment and management of many chronic illnesses,
      neurological disorders, and mental health issues. Examples include: diabetes,
      autism spectrum disorder (ASD), depression, drug addition, and anxiety disorders.
      In this paper, we present a few mobile health technologies developed by our group
      and also discuss emerging opportunities as well as existing challenges.
      Technologies presented include wearable sensors for electrodermal activity (EDA)
      and mobile plethysmography as well as mobile phones and the supporting wireless
      network architecture.

PMID- 21096417
TI  - High performance and resource efficient biological sequence alignment.
AB  - In this paper, we present a novel method based on hardware partitioning to reduce
      the execution time and improve the resource utilization of biological sequence
      align- ment, resulting in a higher performance as compared to conventional
      approaches. The paper shows that the method reduces the execution time and
      improves the resource utilization up to 33.3%. Further, equations are derived,
      showing the general trend of execution time reduction, resource utilization
      improvement and hence performance enhancement.

PMID- 21096418
TI  - Low-coupled parallel strategy for Monte Carlo radiation dose calculation.
AB  - In this work a parallelization technique for Monte Carlo calculation of the
      radiation absorbed dose is presented. The proposed method reduces the overall
      time of calculation exploiting the probabilistic nature of the problem. Reducing
      dose calculation times to meet practical application of use of results is a topic
      of great interest in the Monte Carlo simulation, dosimetry evaluation and
      treatment planning. The general problem of dose calculation parallelization was
      analyzed. The optimal number of calculation units for a given context was also
      determined.

PMID- 21096419
TI  - Non-parametric kernel density estimation for the prediction of neoadjuvant
      chemotherapy outcomes.
AB  - In this paper we propose an application of local statistical models to the
      problem of identifying patients with pathologic complete response (PCR) to
      neoadjuvant chemotherapy. The idea of using local models is to split the input
      space (with data from PCR and NoPCR patients) and build a model for each
      partition. After the construction of the models we used bayesian classifiers and
      logistic regression to classify patients in the two classes.

PMID- 21096420
TI  - SNP analysis of Rac1 For personalized ligand interaction.
AB  - This paper addresses mutational events that give rise to differing response to
      drugs focusing on Rac1, a protein that has been recognized as a target for drug
      design for cardiovascular disease due its regulatory role of angiogenesis. Rac1
      has been considered with reference to Single Nucleotide Polymorphism (SNP), which
      has become of great value for personalized medicine. We have considered four
      variation of Rac1 registered in UNIPROTKB. Two of these variations are due to the
      environmental or population factors and two are mutation that we have selected
      because they are located near the binding sites of Rac1. Rac1 has been modelled
      by Rosetta software and by i-Tasser web server. We have chosen i-Tasser based
      modelling because the Rac1 structure obtained was more closely resembling
      crystallography data. In silico model have been used as receptors for docking
      with a set of 20 morpholines. The results that have been obtained on SNPs shows
      that a single ligand can react very differently with a mutated structure. Our
      analysis shows that all mutations that have been considered change Rac1
      conformation and increase the accessible surface of Rac1. Our analysis highlights
      the effect of two sources of genetic variability: single base variation and
      alternative splicing.

PMID- 21096421
TI  - Exons and introns characterization in nucleic acid sequences by time-frequency
      analysis.
AB  - A current problem in deoxyribonucleic acid (DNA) sequence analysis is to
      determine the exact locations of the genes and also in eukaryotes, the protein
      coding regions in the mRNA primary transcript (pre-mRNA).The conversion into
      discrete numerical values of the symbols associated to the nucleotides of these
      sequences allows for a signal to address the problems related to localization and
      annotation of genes. In this work, thermodynamic data of free energy changes
      (DeltaG degrees ) on the formation of a duplex structure of DNA or RNA are used
      to convert the symbols into numerical values associated with the nucleotide
      sequence pre-mRNA. This study presents an analysis, based on techniques of time
      frequency representation of a large number of gene sequences, in order to find
      variables related to pre-mRNA that could best characterize and discriminate
      coding regions from non-coding regions. It has been found that instantaneous
      frequency variables and instantaneous spectral energy variables in different
      frequency bands, allowed exons and introns to be correctly classified with more
      than 85%.

PMID- 21096422
TI  - Simulation and experimental validation of resonant electric markers used for
      medical device tracking in magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI), which was traditionally used for patient
      diagnosis, has gained in importance in minimally invasive interventions in the
      recent past. Hence, there is an increasing demand for medical devices compatible
      with the MR environment. One of the challenges is to visualize the medical
      devices, e.g. catheters, within the MR image. Several methods exist to cope with
      this task.

PMID- 21096423
TI  - MiMed liver: a planning system for liver surgery.
AB  - In clinical routine of liver surgery there are a multitude of risks such as
      vessel injuries, blood loss, incomplete tumor resection, etc. In order to avoid
      these risks the surgeons perform a planning of a surgical intervention. A good
      graphical representation of the liver and its inner structures is of great
      importance for a good planning. In this work we introduce a new planning system
      for liver surgery, which is meant for computer tomography (CT) data analysis and
      graphical representation. The system is based on automatic and semiautomatic
      segmentation techniques as well as on a simple and intuitive user interface and
      was developed with the intention to help surgeons by planning an operation and
      increasing the efficiency in open liver surgery.

PMID- 21096424
TI  - Real-time cannula navigation in biological tissue with high temporal and spatial
      resolution based on impedance spectroscopy.
AB  - In many medical applications a well-directed positioning of a cannula in body
      tissue is mandatory. Especially the accurate placing of the cannula tip in the
      tissue is important for efficient drug delivery or for accessing blood vessels
      and nerves. This paper presents a new approach for a universal cannula navigation
      system based on tissue classification on the cannula tip by impedance
      spectroscopy. The cannula serves as coaxial, open ended waveguide which is
      connected to remote measurement equipment. Objective of the new system is to
      reach a high spatial and temporal resolution for dynamic cannula guidance.
      Therefore the proposed coaxial cannula design has been analyzed by Finite Element
      Simulation to investigate the sensitivity of the cannula tip. For fast tissue
      impedance spectrum measurement the Time-Domain-Reflectometry method is used in
      order to achieve a high temporal resolution. Measurement data derived in the
      laboratory is analyzed and interpreted using the general Cole-Cole model for
      tissue. Based on the results we propose to use a chirp signal for impedance
      measurement in order to improve the sensitivity of the system towards specific
      tissue properties.

PMID- 21096425
TI  - Tagging module for lesion localization in capsule endoscopy.
AB  - Capsule endoscopes are effective diagnostic tools for the gastro intestinal tract
      disorders at patient's comfort. However the present capsule endoscopes lack
      efficient localization techniques to specify a pathological area that may require
      further diagnosis or treatment. This paper presents the development of a tagging
      module based novel method for the real-time localization of the site of interest.
      The tagging module consists of a bio compatible micro tag, compressed spring with
      a string latch and thermal igniter. The module can be integrated with the capsule
      endoscope and activated using an external trigger signal. On activation, the
      micro tag releases instantly and penetrates the mucosa layer of GI tract, region
      of interest. X-ray imaging is used to detect the location of micro tag embedded
      in GI tract wall. The radiopaque micro tags provide pre-operative valuable
      position information of the infected area to facilitate further clinical
      procedures.

PMID- 21096426
TI  - Energy efficient on-sensor processing in Body Sensor Networks.
AB  - Body Sensor Networks (BSNs) have tremendous potential in facilitating the real
      time monitoring of the health of an individual in their own environment. However
      to truly exploit this potential, the powerful signal processing and analysis
      techniques available in the hospital environment must also be deployed in BSNs.
      In this paper, techniques in algorithm development, communications, hardware
      architecture and circuit design are described that will achieve the necessary
      power savings to make intelligent BSNs a reality.

PMID- 21096427
TI  - Clinical tests and evaluations of a wireless ECG sensor for realization of
      ubiquitous health care systems.
AB  - This paper introduces the concept of an online medical diagnosis system for
      ubiquitous health care using a wireless ECG sensor. To confirm the feasibility
      ofthe system, we conducted clinical tests by 67 subjects with a wireless ECG
      sensor and a Holter ECG monitor simultaneously for comparison purpose. We made
      five types of evaluations such as analyses on data loss rate, burst data loss
      length, ECG waveforms comparison, normalized cross-correlation and heart rate
      variability (HRV) by RR50. The results show that, as long as the sensed data are
      successfully received at a receiver, the wireless ECG sensor has a comparable
      performance with the Holter ECG monitor.

PMID- 21096428
TI  - A fast key generation method based on dynamic biometrics to secure wireless body
      sensor networks for p-health.
AB  - Body sensor networks (BSNs) have emerged as a new technology for healthcare
      applications, but the security of communication in BSNs remains a formidable
      challenge yet to be resolved. The paper discusses the typical attacks faced by
      BSNs and proposes a fast biometric based approach to generate keys for ensuing
      confidentiality and authentication in BSN communications. The approach was tested
      on 900 segments of electrocardiogram. Each segment was 4 seconds long and used to
      generate a 128-bit key. The results of the study found that entropy of 96% of the
      keys were above 0.95 and 99% of the hamming distances calculated from any two
      keys were above 50 bits. Based on the randomness and distinctiveness of these
      keys, it is concluded that the fast biometric based approach has great potential
      to be used to secure communication in BSNs for health applications.

PMID- 21096429
TI  - FIREGUIDE: Firefighter guide and tracker.
AB  - In this paper, we introduce an indoor location tracking and navigation system
      (FIREGUIDE) using Bluetooth and RFID technology. FIREGUIDE assists the
      firefighters to find the nearest exit location and presents the Incident
      Commander the current firefighter's location superimposed on a map of the
      building floor. We envision that the FIREGUIDE system will save significant
      number of fire fighters and victims' lives.

PMID- 21096430
TI  - Changes in frequency of seizure-like events in stimulated cortical slices.
AB  - Epilepsy affects nearly 3 million people in the United States alone. Given the
      fact that many people suffer from seizures that are intractable to
      pharmacological intervention, research groups are investigating the use of
      electrical stimulation to interact with and ameliorate symptoms of epileptic
      seizures. In mouse cortical slices made seizuregenic through chemical means, we
      applied precision controlled current pulses and measured local field potentials
      through a four point probe system to investigate the response of seizing tissue
      to electrical stimulation. We have determined that the frequency of the
      spontaneous seizure-like events may be modified by low amplitude, current
      controlled stimulation (0.5 microA). Differently from previously thought, this
      change in frequency is however not accompanied by any alteration of the tissue
      permittivity or conductivity during the inter-seizure interval.

PMID- 21096431
TI  - Mobile communications for monitoring heart disease and diabetes.
AB  - This paper describes a practical development project to enable the monitoring of
      vital signs data obtained from patients located in remote rural locations. The
      data are gathered from a wireless network of sensors attached to a patient's body
      and stored locally for secure transmission over existing communication
      infrastructures to a hospital server. Clinicians are then able to monitor the
      patient offline and upload diagnoses.

PMID- 21096432
TI  - Feasibility of congestive heart failure telemanagement using a wii-based telecare
      platform.
AB  - A gaming platform has been used to implement a Home Automated Telemanagement
      (HAT) system for chronic disease management in the patient's home. The system
      questions patients with congestive heart failure (CHF) to monitor symptoms,
      weight changes, and quality of life while educating the patient on their disease.
      The system is designed to run on the Nintendo Wii videogame console using an
      active internet connection and the console's built in internet browser. It
      questions the patient daily on their condition, monitors their weight, and
      provides the patient with instant feedback on their condition in the form of a 3
      zone CHF action plan. The system is designed to be as simple as possible, making
      it usable by patients with no prior computer or videogame experience. This
      telemanagement system has been successfully designed and implemented to optimize
      the care of patients with CHF.

PMID- 21096433
TI  - Influence of tear configuration on false and true lumen haemodynamics in type B
      aortic dissection.
AB  - The management and follow-up of chronic type B aortic dissections continues being
      a clinical challenge. Patients with chronic type B dissection have high mid/long
      term mortality mainly due to progressive aortic dilatation and subsequent
      rupture.

PMID- 21096434
TI  - Development of miniaturized mass-flow meter for an axial flow blood pump using a
      curved cannula.
AB  - To grasp conditions of patients and implantable artificial hearts, it is
      important to measure the pump flow rate continuously and noninvasively. In this
      study, a miniaturized mass-flow meter for discharged patients with an implantable
      axial flow blood pump was developed. The mass-flow meter makes use of centrifugal
      force generated by mass-flow rate around the curved cannula. Based on the
      computational fluid dynamics (CFD) analysis, the prototype miniaturized mass-flow
      meter was developed. Two strain gauges were adopted as the sensor elements. The
      first strain gauge, attached to the straight area, measured static pressure. The
      second strain gauge, attached to the curved area, measured static pressure and
      the centrifugal force. By subtracting the output of the first strain gauge from
      the output of the second strain gauge, the mass-flow rate was determined. In the
      evaluation tests using the mock-up circulation loop, the mass-flow meter was
      compared to a commercial flow meter. As a result, measurement error was less than
      1.0 L/min, and time delay was less than 0.2 s. We confirmed that the miniaturized
      mass-flow meter could accurately measure the mass-flow rate continuously and
      noninvasively.

PMID- 21096435
TI  - In vivo validation of pulsatile flow and differential pressure estimation models
      in a left ventricular assist device.
AB  - Implantation of sensors to measure hemodynamic parameters such as pulsatile pump
      flow and differential pressure (head) in an implantable rotary pump (IRBP)
      requires regular in situ calibration due to measurement drift. In addition, risks
      associated with sensor failure and thrombus formation makes the long-term
      implantation in patients problematic. In our laboratory, two stable and novel
      dynamical models for non-invasive pulsatile flow and head estimation were
      proposed and tested in vitro using mock circulatory loop experiments with varying
      hematocrit (HCT). Noninvasive measurements of power and pump speed were used as
      inputs to the flow model while the estimated flow was used together with the pump
      rotational speed as inputs to the head estimation model. In this paper, we
      evaluated the performance of the proposed models using in vivo experimental data
      obtained from greyhound dogs (N=5). Linear regression analysis between estimated
      and measured pulsatile flows resulted in a highly significant correlation (R(2) =
      0.946) and mean absolute error (e) of 0.810 L/min, while for head, R(2) = 0.951
      and e = 10.13 mmHg were obtained.

PMID- 21096436
TI  - Improvement of artery radii determination with single ultra sound channel
      hardware & in vitro artificial heart system.
AB  - In several clinical and experimental circumstances, it is widely necessary to
      characterize the bio-mechanical changes induced by atherosclerosis to the
      arterial wall. In this context, the purpose of this paper is twofold. Firstly, to
      propose a low cost ultrasound setup to improve artery radii determination in
      elasticity experiments, based on two transducers using a single channel
      ultrasound hardware. Secondly, to present an in vitro artificial heart system
      developed in our laboratory, which provides a wide range of hemodynamic
      parameters in arterial elasticity assessment experiments. It can be used in a
      liquid, stand alone mode or blowing air to a Jarvik device. This system will be
      integrated in future works with the proposed ultrasound setup to provide real
      time elasticity measurements.

PMID- 21096437
TI  - Real time conductance catheter system based on FPGA.
AB  - This paper presents a digital conductance catheter system based on FPGA (Field
      Programmable Gate Arrays) to measure real time ventricular volumes for
      experimental use. The system performance is realized in three stages: a)
      conductance measurements using a well-known set of resistance connected to each
      catheter section; b) volumes measurements in glass containers of well-known
      geometry that contain a solution with a resistivity similar to the blood, and c)
      comparison between the previous analog conductance catheter system and this novel
      FPGA based system.

PMID- 21096438
TI  - Heart rate and blood pressure variability effects as a result of oxygen and
      nitrous oxide administration in the anesthetized mouse.
AB  - This study examines the effects of changing oxygen fractional inspiration ratio
      (FiO(2)), and nitrous oxide (N(2)O) for the improvement of cardiovascular control
      of mean arterial blood pressure (MAP) and heart rate (HR) in C57BL/6 mice under
      isoflurane anesthesia (1.5%) for up to 90 minutes post-induction. Heart rate
      variability (HRV) indices are also quantified under these conditions. The results
      indicate that changing the FiO(2) does result in lower MAP and HR values compared
      to the case of N(2)O (50%) administration to the isoflurane gas mixture. HRV
      indices declined over the course of all anesthetic regimens, suggesting a
      decrease in parasympathetic tone. We conclude that the most optimal anesthetic
      condition is achieved when N(2)O (50%) is added to the gas mixture.

PMID- 21096439
TI  - Non-invasive assessment of atherosclerotic plaques effects on the segment-to
      segment human carotid visco-elasticity and filtering.
AB  - Although a variety of factors have been proposed as key factors of the
      atherosclerotic plaque vulnerability, the mechanisms that contribute to this
      problem are not yet fully characterized. In previous works we demonstrated that
      changes in arterial wall viscosity and elasticity and/or in the filtering
      function (FF) could be in the basis of arterial wall alterations. If these
      properties are altered in arterial wall with atherosclerotic plaques remain to be
      analyzed. Our aims were to analyze, the arterial wall visco-elasticity and FF of
      human carotid arteries with atherosclerotic plaques. To this end, instantaneous
      arterial diameter waveforms were obtained non-invasively (B-Mode Echography), in
      five sites (S1-S5) on the carotid artery. After that, diameter waveform obtained
      in S1 (first segment of the common carotid artery) was calibrated using pressure
      values, and used to quantify the pressure-diameter relationship for each segment.
      From pressure-diameter relationships, viscosity, elasticity and FF were
      quantified. Central portions of atherosclerotic plaques showed a reduced FF. At
      least in theoretical terms, the FF reduction could be related with the plaque
      vulnerability.

PMID- 21096440
TI  - Conduction abnormalities in the right ventricular outflow tract in Brugada
      syndrome detected body surface potential mapping.
AB  - Brugada syndrome (BrS) causes sudden death in patients with structurally normal
      hearts. Manifestation of BrS in the ECG is dynamical and most patients do not
      show unequivocal signs of the syndrome during ECG screening. We have obtained 67
      lead body surface potential mapping recordings of 25 patients with BrS and
      analyzed their spatial distribution of surface potentials during ventricular
      activation. Six patients presented spontaneous type I ECGs during the recording.
      These patients showed non-dipolarities in isopotential maps at the right
      ventricular outflow tract (RVOT) region during the development of terminal R
      waves in right precordial leads. Same finding was observed in 95% of BrS patients
      not presenting a type I ECG. Conduction delay in the RVOT may be a consistent
      finding in BrS patients that can be identified by Body Surface Potential Mapping.

PMID- 21096441
TI  - A 2D-computer model of atrial tissue based on histographs describes the electro
      anatomical impact of microstructure on endocardiac potentials and electric near
      fields.
AB  - In experiments with cardiac tissue, local conduction is described by waveform
      analysis of the derivative of the extracellular potential Phi(e) and by the loop
      morphology of the near-field strength E (the components of the electric field
      parallel and very close to the tissue surface). The question arises whether the
      features of these signals can be used to quantify the degree of fibrosis in the
      heart. A computer model allows us to study the behavior of electric signals at
      the endocardium with respect to known configurations of microstructure which can
      not be detected during the electrophysiological experiments. This work presents a
      2D-computer model with sub-cellular resolution of atrial micro-conduction in the
      rabbit heart. It is based on the monodomain equations and digitized histographs
      from tissue slices obtained post-experimentum. It could be shown that excitation
      spread in densely coupled regions produces uniform and anisotropic conduction. In
      contrast, zones with parallel fibers separated by uncoupling interstitial space
      or connective tissue may show uniform or complex signals depending on pacing
      site. These results suggest that the analysis of Phi(e) and E combined with multi
      site pacing could be used to characterize the type and the size of fibrosis.

PMID- 21096442
TI  - Cardiac output assessment using oxygen consumption estimated from the left
      ventricular pressure-volume area.
AB  - Use of a majority of structural variables (age, sex, height) to estimate oxygen
      consumption in the calculation of cardiac output (CO) by the Fick principle does
      not account for changes in physiological conditions. To improve this limitation,
      oxygen consumption was estimated based on the left ventricular pressure-volume
      area. A pilot study with 10 patients undergoing right cardiac catheterization
      showed that this approach was successful to estimate CO (r=0,73, vs.
      thermodilution measured CO). Further essays changing end-diastolic-volume in the
      pressure-volume area formula by body weight or body surface area showed that this
      last yielded the best correlation with the thermodilution measured CO (slope=1,
      ordinate =0.01 and r=0.93). These preliminary results indicate that use of a
      formula originated from the pressure-volume-area concept is a good alternative to
      estimate oxygen consumption for CO calculation.

PMID- 21096443
TI  - Seasonal chaotic features of pulse rate in a healthy subject and a patient after
      coronary stenting.
AB  - This study analyzes seasonal features of pulse rate chaos in both healthy and
      unhealthy subjects. Analytical methods, such as numerical titration, sample
      entropy and spectral analysis, were used to detect and estimate the seasonal
      fluctuations in chaotic attributes, complexity and nonlinearity of pulse rate.
      Chaotic feature analyses are based on pulse rate data collected over one year
      from a healthy male and a male patient after coronary stenting. The results show
      that the mean level of pulse rate chaos in the healthy subject is lowest in
      winter (values of NL, DR, and SampEn are 8.1 +/- 0.3%, 41.0 +/- 1.2%, and 1.98 +/
      0.02, separately) and highest in summer (corresponding values are 9.9 +/- 0.6%,
      46.8 +/- 2.3%, and 2.06 +/- 0.03, separately) (P < 0.05), whereas the
      postoperative individual has a relatively lower mean chaotic dynamics that is
      least active in autumn (7.1 +/- 0.5%, 14.8 +/- 1.5%, and 0.80 +/- 0.01) and more
      active in winter (7.7 +/- 0.4%, 35.9 +/- 1.9%, and 0.93 +/- 0.01) and spring (9.1
      +/- 0.7%, 28.6 +/- 2.1%, and 0.87 +/- 0.01) (P < 0.05). The study reveals
      distinct seasonal autonomic and cardiac activities in both good health and
      disease. These findings may also pave the way for developing new approaches to
      monitoring long-term HRV and interpreting HRV chaotic features.

PMID- 21096444
TI  - Modeling of human Heart Rate response during walking, cycling and rowing.
AB  - The aim of this paper is to study the human Heart Rate (HR) response during
      walking, cycling and rowing exercises using linear time varying (LTV) models. We
      used the frequency of exercise locomotion as the input to the model. This
      frequency characterizes the stride rate, cadence rate and strokes rate of the
      walking, cycling and rowing exercises respectively. The time varying parameters
      in the LTV models were estimated by the Kalman Filter (KF). The results in this
      study demonstrate that HR responses to these exercises exhibit some degree of
      time varying nature.

PMID- 21096445
TI  - Heart and respiratory rate detection on a bathroom scale based on the
      ballistocardiogram and the continuous wavelet transform.
AB  - Ballistocardiography is a non-invasive technique that yields information about
      the cardiovascular system that is not available in other external signals such as
      the electrocardiogram (ECG). In the last years, several research groups have
      obtained the ballistocardiogram (BCG) by using instrumentation methods simpler
      than those available in the 1950s and that did not progress because of their
      complexity as compared to ultrasound and other noninvasive techniques that are in
      common use nowadays. We describe a novel method for real-time robust heart- (HR)
      and respiratory- (RR) rate detection from a subject that stands on a common
      electronic bathroom scale. BCG signals from the scale are wirelessly sent to a PC
      where algorithms based on the continuous wavelet transform (CWT) extract the HR
      and the RR. HR results are compared to those obtained from the ECG. To better
      assess the RR results, subjects have been asked to synchronize their breathing
      rate to an on-screen bar-graph set at a constant rate of breaths per minute. This
      method to obtain the heart and respiratory rates is simple, compact, non-invasive
      and passive, and can be applied to any person able to stand on an electronic
      weighing scale, even if wearing shoes.

PMID- 21096446
TI  - Analysis of QRS loop in the Vectorcardiogram of patients with Chagas' disease.
AB  - In the present work, we have studied the QRS loop in the Vectorcardiogram (VCG)
      of 95 chronic chagasic patients classified in different groups (I, II and III)
      according to their degree of myocardial damage. For comparison, the VCGs of 11
      healthy subjects used as control group (Group O) were also examined. The QRS loop
      was obtained for each patient from the XYZ orthogonal leads of their High
      Resolution Electrocardiogram (HRECG) records. In order to analyze the variations
      of QRS loop in each detected beat, it has been proposed in this study the
      following vectorcardiographic parameters a) Maximum magnitude of the cardiac
      depolarization vector, b) Volume, c) Area of QRS loop, d) Ratio between the Area
      and Perimeter, e) Ratio between the major and minor axes of the QRS loop and f)
      QRS loop Energy. It has been found that one or more indexes exhibited statistical
      differences (p < 0.05) between groups 0-II, O-III, I-II, I-III and II-III. We
      concluded that the proposed method could be use as complementary diagnosis
      technique to evaluate the degree of myocardial damage in chronic chagasic
      patients.

PMID- 21096447
TI  - A new ECG biomarker for drug toxicity: a combined signal processing and
      computational modeling study.
AB  - QT prolongation is the only clinically proven, yet insufficient,
      electrocardiogram (ECG) biomarker for drug-induced cardiac toxicity. The goal of
      this study is to evaluate whether JT area, i.e., total area of the T-wave, can
      serve as an ECG biomarker for drug-induced cardiac toxicity using both signal
      processing and computational modeling approaches. An ECG dataset that contained
      recordings from patients under control and sotalol condition was analyzed. In
      order to relate sotalol-induced ECG changes to its effect on ion channel level,
      i.e., blockade of the rapid component of the delayed rectifier potassium channel
      (I(Kr)), varied degrees of I(Kr) blockade were simulated in a slab of ventricular
      tissue. The mean JT area increased by 36.5% following the administration of
      sotalol in patients. Simulations in the slab tissue showed that sotalol increased
      action potential duration preferentially in the midmyocardium, which led to
      increased transmural dispersion of repolarization and JT area. In conclusion, JT
      area reflects the transmural dispersion of repolarization and may be a
      potentially useful surrogate/supplemental ECG biomarker to assess drug safety.

PMID- 21096448
TI  - Using PIV to determine relative pressures in a stenotic phantom under steady flow
      based on the pressure-poisson equation.
AB  - Pressure gradient across a Gaussian-shaped 87% area stenosis phantom was
      estimated by solving the pressure Poisson equation (PPE) for a steady flow
      mimicking the blood flow through the human iliac artery. The velocity field
      needed to solve the pressure equation was obtained using particle image
      velocimetry (PIV). A steady flow rate of 46.9 ml/s was used, which corresponds to
      a Reynolds number of 188 and 595 at the inlet and stenosis throat, respectively
      (in the range of mean Reynolds number encountered in-vivo). In addition,
      computational fluid dynamics (CFD) simulation of the same flow was performed.
      Pressure drops across the stenosis predicted by PPE/PIV and CFD were compared
      with those measured by a pressure catheter transducer. RMS errors relative to the
      measurements were 17% and 10% for PPE/PIV and CFD, respectively.

PMID- 21096449
TI  - Improvements of scale fourier linear combiner for impedance cardiography
      analysis.
AB  - In this paper, we present two additions to the SFLC algorithm in order to improve
      the beat by beat estimation of fiducial points (B and X) and the maximum value of
      the derivative in impedance cardiography signal: addition of a reference input
      and scanning each beat more than once. On data synthesized from real ICG which
      exhibits beat by beat changes and baseline variations, we used statistical
      measures to show that the modified algorithms give accurate beat by beat
      estimation conversely to the original version of SFLC. We also give results on a
      real ICG using phono cardiography as a reference. In this case too, results show
      the pertinence of the proposed improvements.

PMID- 21096450
TI  - Optimal set of EEG electrodes for rapid serial visual presentation.
AB  - In our application, the goal is to search through a large image to find all
      instances of a pre-specified, high-valued target. One approach taken to increase
      the throughput of this image search task is to: chop the large image into
      numerous small images, display them to a user at high rates one-at-a-time, and
      then search the simultaneously-recorded EEG data for neural activity that
      signifies that the user detected an instance of the target. The temporal
      efficiency of this EEG-based system is reduced by the overhead, which increases
      as the number of electrodes increases. Hence, we wish to find a minimal set of
      electrodes that ideally maintains the detection performance. In order to inform
      the design of future EEG-based image search systems, in this paper we find the 12
      out of 32/64 most important electrodes for detection using 5 different feature
      selection methods. The optimal set includes all 5 occipital and the 2 most
      frontal electrodes.

PMID- 21096451
TI  - Tailoring the drug loading capacity of polypyrrole films for use in intraocular
      biomicrorobots.
AB  - Preliminary results concerning impregnation of polypyrrole (Ppy) films with
      rhodamine B (Rh-B) are presented. The films are envisioned to be functional
      surface coatings on biomicrorobots for controlled drug delivery. The polypyrrole
      films were obtained on gold substrates by anodic oxidation of pyrrole in aqueous
      solutions containing sodium dodecylbenzenesulfonate (SDBS) as doping agent. The
      influence of the sodium doping level on the wettability of the Ppy surfaces, and
      the loading capacity of Rh-B is systematically analyzed. The undoping of the
      films results in the formation of surface microcracks and tends to make the
      surface hydrophobic in nature, which subsequently leads to an increase of the
      adsorption capacity of Rh-B on the Ppy deposit. This controllable increase in
      adsorption capacity provides an opportunity to tailor the drug loading capacity
      of Ppy films.

PMID- 21096452
TI  - Cell micromanipulation with an active handheld micromanipulator.
AB  - The paper describes the use of an active handheld micromanipulator, known as
      Micron, for micromanipulation of cells. The device enables users to manipulate
      objects on the order of tens of microns in size, with the natural ease of use of
      a fully handheld tool. Micron senses its own position using a purpose-built
      microscale optical tracker, estimates the erroneous or undesired component of
      hand motion, and actively corrects it by deflecting its own tool tip using
      piezoelectric actuators. Benchtop experiments in tip positioning show that active
      compensation can reduce positioning error by up to 51% compared to unaided
      performance. Preliminary experiments in bisection of sea urchin embryos exhibit
      an increased success rate when performed with the help of Micron.

PMID- 21096453
TI  - Effect of the chain of magnetosomes embedded in magnetotactic bacteria and their
      motility on magnetic resonance imaging.
AB  - This paper investigates the influence of the magnetosome's chain, the motility,
      and the bacterial cell of MC-1 magnetotactic bacteria (MTB) on the Magnetic
      Resonance imaging (MRI) contrast. Because of its embedded magnetic nanoparticles,
      that allow magnetic guidance and imaging contrast generation under MRI,
      magnetotactic bacteria are being considered for therapeutic drug delivery to
      tumors. In order to separately investigate the different potential sources of
      contrast in MRI, we used three samples of MC-1 MTB. The first sample was
      constituted of magnetic bacteria that successfully synthesize magnetic
      nanoparticles. MC-1 bacteria that do not synthesize magnetosomes form the second
      sample while the third sample is constituted from dead MC-1 magnetic bacteria
      containing magnetic nanoparticle. T(2)-weighted magnetic resonance images were
      obtained for multiple echo times. T(2) was then estimated by fitting the signal
      intensity data for different echo time values to a monoexponential decay curve.
      It is found that nanoparticles synthesized by MC-1 MTB are the predominant source
      of contrast in MRI over motion and the cell body.

PMID- 21096454
TI  - Magnetotactic bacteria penetration into multicellular tumor spheroids for
      targeted therapy.
AB  - Preliminary experiments showed that MC-1 magnetotactic bacteria (MTB) could be
      used for the delivery of therapeutic agents to tumoral lesions. Each bacterium
      can provide a significant thrust propulsion force generated by two flagella
      bundles exceeding 4pN. Furthermore, a chain of single-domain magnetosomes
      embedded in the cell allows computer directional control and tracking using a
      magnetic resonance imaging (MRI) system. Although these embedded functionalities
      suggest that MTB when under the influence of an external computer could be
      considered as biological microrobots with the potential of targeting tumors,
      little is known about their level of penetration in tumoral tissues. In this
      paper, in vitro experiments were performed to assess the capability of these
      bacteria to penetrate tumor tissue for the delivery of therapeutic agents.
      Multicellular tumor spheroids were used since they reproduce many properties of
      solid tumors. The results show the ability of these MTB when submitted to a
      directional magnetic field to penetrate inside a 3D multicellular tumor spheroid
      through openings present in the tissue.

PMID- 21096455
TI  - A locomotion mechanism with external magnetic guidance for active capsule
      endoscope.
AB  - Gastrointestinal (GI) disorder is one of the most common diseases in human body.
      The swallowable wireless capsule endoscopy has been proved to be a convenient,
      painless and effective way to examine the whole GI tract. However, lack of motion
      control makes the movement of the capsule substantially random, resulting in
      missing diagnosis. In this paper, a locomotion mechanism is developed for the
      next-generation active capsule endoscope. An internal actuator integrated on
      board the capsule is designed to provide driving force and improve the dexterity.
      A small permanent magnet enclosed inside the capsule interacts with an external
      magnetic field to control the capsule's orientation and offer extra driving
      force. This mechanism avoids sophisticated and bulky control system and reduces
      power consumption inside the capsule. Ex-vivo experimental results showed that it
      can make a controllable movement inside the porcine large intestine. The
      mechanism also has the potential to be a platform for further development, such
      as devices of operations, spraying medicine, biopsy etc.

PMID- 21096456
TI  - 2D mapping of strongly deformed cell nuclei based on contour warping.
AB  - The dynamics of genome regions are associated to the functional or dysfunctional
      behaviour of the human cell. In order to study these dynamics it is necessary to
      remove perturbations coming from movement and deformation of the nucleus, i.e.
      the container holding the genome. In literature models have been proposed to cope
      with the transformations corresponding to nuclear dynamics of healthy cells.
      However for pathological cells, the nucleus deforms in an apparently random way,
      making the use of such models a non trivial task. In this paper we propose a
      mapping of the cell nucleus which is based on the matching of the nuclear
      contours. The proposed method does not put constraints on the possible shapes nor
      on the possible deformations, making this method suited for the analysis of
      pathological nuclei.

PMID- 21096457
TI  - Deformable registration of retinal fluorescein angiogram sequences using
      vasculature structures.
AB  - State-of-the-art deformable registration algorithms do not perform as well with
      FA sequences because they are designed to deal with changes of content appearance
      (e.g., due to different sensors imaging the same organs) but not with content
      changes, which occur throughout a FA sequence as different portions or the
      vascular structure are visible (perfused) in different frames. This paper
      presents a frame-to-frame registration algorithm for ultra-wide-field-of-view
      (UWFV) fluorescein angiograms (FA) of the retina, based on deformable alignment
      of the retinal vasculature structure. Comparative experiments on an initial set
      of UWFV FAs indicate that, thanks to its specialization, our technique
      outperforms one of the best state-of-the-art methods for multimodal image
      registration when dealing with the demanding characteristics of the UWFV FA
      sequences.

PMID- 21096458
TI  - 2D/3D reconstruction of a scaled lumbar vertebral model from a single
      fluoroscopic image.
AB  - Accurate three-dimensional (3D) models of lumbar vertebrae can enable image-based
      3D kinematic analysis. The common approach to derive 3D models is by direct
      segmentation of CT or MRI datasets. However, these have the disadvantages that
      they are expensive, time-consuming and/or induce high-radiation doses to the
      patient. In this paper, we present a technique to reconstruct a scaled 3D lumbar
      vertebral model from a single two-dimensional (2D) lateral fluoroscopic image and
      a statistical shape model of the lumbar vertebrae. Four cadaveric lumbar spine
      segments (totally twelve lumbar vertebrae) were used to validate the technique.
      To evaluate the reconstruction accuracy, the surface models reconstructed from
      the lateral fluoroscopic images were compared to the associated ground truth data
      derived from a 3D CT-scan reconstruction technique. For each case, a surface
      based matching was first used to recover the scale and the rigid transformation
      between the reconstructed surface models and the ground truth model before the
      distances between the two discrete surface models were computed. An average error
      of 1.0 mm was found when the present technique was used to reconstruct the
      surface models of all twelve lumbar vertebrae.

PMID- 21096459
TI  - A new representation of intensity atlas for GPU-accelerated instance generation.
AB  - Fast instance generation is a key requirement in atlas-based registration and
      other problems that need a large number of atlas instances. This paper describes
      a new method to represent and construct intensity atlases. Both geometry and
      intensity information are represented using B-spline deformation lattices;
      intensities are approximated using the multi-level B-spline approximation
      algorithm during model creation and the parallel computation capability of modern
      graphics processing units is used to accelerate the process of instance
      generation. Experiments with distal radius CTs show that, with a coefficients-to
      voxels ratio of 0.16, intensities can be approximated up to an average accuracy
      of 2 +/- 17 grey-levels (out of 3072 total grey-levels), and instances of
      resolution 256*256*200 can be produced in a rate of 25 instances per second with
      a GeForce GTX 285 video card, which is about 500 times performance improvement
      over the traditional method that uses plain CPU.

PMID- 21096460
TI  - Using Fitts's law for evaluating Tongue Drive System as a pointing device for
      computer access.
AB  - In this paper, the results of a 2-D center-out task in a Fitts's law experiment
      have been presented for measuring the performance of the Tongue Drive System
      (TDS). Although the end-user population for TDS is individuals with tetraplegia,
      in this study, we recruited 6 able-bodied subjects in 3 sessions, conducted in 3
      consecutive days. They performed the same task with their right hand using a
      standard mouse for achieving a baseline as well as a standard keypad with their
      right index finger. The resulting average throughput for TDS, keypad, and mouse
      were 1.67, 2.17, and 3.99 bit/s, respectively.

PMID- 21096461
TI  - Early results on wrist based heart rate monitoring using mechanical transducers.
AB  - Heart rate monitoring has been a significant topic of interest in the areas of
      healthcare, sports and gaming. Compared to locations such as the neck, ear, or
      chest, the wrist is a convenient measurement point, as the measurement technology
      can be integrated into a wristwatch. However, key technical challenges exist,
      namely a small physiological SNR and large disturbances due to motion artifact.
      This paper reports early results on a packaging concept to monitor the heartrate
      during rest and motion using off-the-shelf piezoelectric PVDF film sensors.
      Evaluation has shown good results at rest and unsatisfactory results during
      motion. Results from this investigation will nonetheless be used as input for the
      development of a wrist-based heartrate monitor which could function during
      activities such as running, walking or typing on a keyboard.

PMID- 21096462
TI  - Home monitoring of patients with Parkinson's disease via wearable technology and
      a web-based application.
AB  - Objective long-term health monitoring can improve the clinical management of
      several medical conditions ranging from cardiopulmonary diseases to motor
      disorders. In this paper, we present our work toward the development of a home
      monitoring system. The system is currently used to monitor patients with
      Parkinson's disease who experience severe motor fluctuations. Monitoring is
      achieved using wireless wearable sensors whose data are relayed to a remote
      clinical site via a web-based application. The work herein presented shows that
      wearable sensors combined with a web-based application provide reliable
      quantitative information that can be used for clinical decision making.

PMID- 21096463
TI  - Wireless transmission of cardiac action potentials with ultrasonically guided
      insertion of silicon probes.
AB  - This paper reports on the coupling of ultrasonically guided cardiac probes with
      wireless transmission of cardiac action potentials for applications in monitoring
      the 3D electrical onset of ventricular fibrillation. An application specific
      integrated circuit has been designed with a 40 dB amplifying stage and a
      frequency modulating oscillator to wirelessly transmit the recorded action
      potentials. Combined with the ultrasonically inserted cardiac probe that reduces
      penetration force, this system demonstrates the initial results in wireless
      monitoring of 3D action potential propagation.

PMID- 21096464
TI  - A miniature, wearable activity/fall monitor to assess the efficacy of mobility
      therapy for children with cerebral palsy during everyday living.
AB  - Children with cerebral palsy may have difficulty walking and may fall frequently,
      resulting in a decrease in their participation in school and community
      activities. It is desirable to assess the effectiveness of mobility therapies for
      these children on their functioning during everyday living. Over 50 hours of tri
      axial accelerometer and digital video recordings from 35 children with cerebral
      palsy and 51 typically-developing children were analyzed to develop algorithms
      for automatic real-time processing of the accelerometer signals to monitor a
      child's level of activity and to detect falls. The present fall-detection
      algorithm has 100% specificity and a sensitivity of 100% for falls involving
      trunk rotation. Sensitivities for drops to the knees and to the bottom are 72%
      and 78%, respectively. The activity and fall-detection algorithms were
      implemented in a miniature, battery-powered microcontroller-based activity/fall
      monitor that the child wears in a small fanny pack during everyday living. The
      monitor continuously logs 1-min. activity levels and the occurrence and
      characteristics of each fall for two-week recording sessions. Pre-therapy and
      post-therapy recordings from these monitors will be used to assess the efficacies
      of alternative treatments for gait abnormalities.

PMID- 21096466
TI  - Predictability of protein subcellular locations by pattern recognition
      techniques.
AB  - An analysis of the predictability of subcellular locations is performed by using
      simple pattern recognition techniques in an attempt to capture the real
      dimensions of the problem at hand. Results show that there are some particular
      locations that does not need of high complexity classification models to be
      predicted with high accuracies, and some partial biological explanations are
      formulated. All the experiments were carried out over a set of Arabidopsis
      Thaliana proteins and classes were defined according to the plants GO slim.

PMID- 21096465
TI  - Development of mobile psychiatry for bipolar disorder patients.
AB  - Managing bipolar disorder is an increasingly important healthcare issue as the
      global prevalence of this condition grows. A widely practiced method of
      monitoring the course of the disorder is by mood and general mental health
      questionnaires. However, current mobile technology provides a potential means of
      monitoring the behavior of individuals and this information could be of value for
      recognizing changes in routine that could be indicative of an upcoming bipolar
      episode. This article explores the potential of utilizing geospatial information
      and indicators of social interaction to enable mobile psychiatry.

PMID- 21096467
TI  - Adaptive threshold for detecting differentially expressed genes in microarray
      data - a simulation study to investigate its performance.
AB  - To detect changes in gene expression data from DNA microarrays, a fixed threshold
      value is used in various studies. However, it is not always guaranteed that a
      threshold value which is appropriate for highly expressed genes is suitable for
      genes with low expression. To address this issue, we have proposed adaptive
      threshold, which has different values for different expression levels. In this
      study, the performance of the adaptive threshold method was investigated through
      simulations. The sensitivity in various noise conditions was in a range between
      72.7 and 100% while the specificity was better than 99% for all noise conditions.
      These results demonstrated the good performance of the proposed method.

PMID- 21096469
TI  - Accurate samples for testing mass spectrometry based peptide quantification
      algorithms.
AB  - Quantitative proteomic experiments use algorithms to estimate peptide abundances
      from spectra. The efficacy of these algorithms is usually tested against a
      contrived mixture of proteins. However, the numerous error sources in mass
      spectrometry based proteomics experiments must be accounted for to evaluate novel
      algorithms in an unbiased manner. We set out to examine how to best utilize a set
      of calibration data for this purpose. We demonstrated that calibration data will
      have substantial noise whose magnitude depends on whether comparisons are made
      within or across experiments. We then propose a novel method of testing
      algorithms that uses the natural isotopic envelope of peptides to minimize
      measurement noise. We show that the variability of isotopic peptide ratios is an
      order of magnitude lower with this approach than with typical standard protein
      mixtures. We conclude by demonstrating the usefulness of this new technique in
      the analysis of typical peak picking algorithms.

PMID- 21096468
TI  - Towards a digital model of zebrafish embryogenesis. Integration of cell tracking
      and gene expression quantification.
AB  - We elaborate on a general framework composed of a set of computational tools to
      accurately quantificate cellular position and gene expression levels throughout
      early zebrafish embryogenesis captured over a time-lapse series of in vivo 3D
      images. Our modeling strategy involves nuclei detection, cell geometries
      extraction, automatic gene levels quantification and cell tracking to reconstruct
      cell trajectories and lineage tree which describe the animal development. Each
      cell in the embryo is then precisely described at each given time t by a vector
      composed of the cell 3D spatial coordinates (x; y; z) along with its gene
      expression level g. This comprehensive description of the embryo development is
      used to assess the general connection between genetic expression and cell
      movement. We also investigate genetic expression propagation between a cell and
      its progeny in the lineage tree. More to the point, this paper focuses on the
      evolution of the expression pattern of transcriptional factor goosecoid (gsc)
      through the gastrulation process between 6 and 9 hours post fertilization (hpf).

PMID- 21096470
TI  - An information theory-based tool for characterizing the interaction environment
      of a protein.
AB  - In recent years large amounts of information have been accumulated in proteomic,
      genetic and metabolic databases. Much effort has been dedicated to developing
      methods that successfully exploit, organize and structure this information.
      However, there is no application, that we know of, that semantically
      characterizes the interaction environment in which a protein exists. A high
      throughput software package has been developed to retrieve information from
      publicly available databases, such as the Gene Ontology Annotation (GOA) database
      and the Human Proteome Resource Database (HPRD) and structure their information.
      This information is presented to the user as groups of semantically described
      dense interaction subnetworks that interact with a target protein.

PMID- 21096471
TI  - Quantitative description of the state of awareness of patients in vegetative and
      minimally conscious state.
AB  - Clinical scales represent the golden standard in characterizing awareness for
      patients in vegetative or in a minimally conscious state. Clinical scales suffer
      from problems of sensitivity, specificity, subjectivity, and inter-rater
      reliability. This leads to a misdiagnosis rate of up to 40% and consequences
      associated with inappropriate treatment decisions. In this study, objective
      measures including physiological and neurological signals are used to quantify
      the patient status. Using linear backward regression analysis, 13 variables
      (based on frequency analysis of the electrocardiogram, heart rate variability,
      amplitude and latency of the P300, skin conductance responses, changes in the
      blood pressure and respiration signal) were found to be sufficient to describe
      74.7% of the variability of the scores. In this regression model, the P300,
      electrocardiogram and the blood pressure signal account for most of the
      variability. More patient data and additional measures will enable refinement of
      the methods. This new objective-measurement based model of the state of awareness
      will complement the clinical scales in order to increase the quality of
      diagnosis.

PMID- 21096472
TI  - Predicting temporal lobe epileptic seizures based on zero-crossing interval
      analysis in scalp EEG.
AB  - A novel real-time patient-specific algorithm to predict epileptic seizures is
      proposed. The method is based on the analysis of the positive zero-crossing
      intervals in the scalp electroencephalogram (EEG), describing the brain dynamics.
      In a moving-window analysis, the histogram of these intervals in each EEG epoch
      is computed, and the distribution of the histogram value in specific bins,
      selected using interictal and preictal references, is estimated based on the
      values obtained from the current epoch and the epochs of the last 5 min. The
      resulting distribution for each selected bin is then compared to two reference
      distributions (interictal and preictal), and a seizure prediction index is
      developed. Comparing this index with a patient-specific threshold for all EEG
      channels, a seizure prediction alarm is finally generated. The algorithm was
      tested on approximately 15.5 hours of multichannel scalp EEG recordings from
      three patients with temporal lobe epilepsy, including 14 seizures. 86% of
      seizures were predicted with an average prediction time of 20.8 min and a false
      prediction rate of 0.12/hr.

PMID- 21096473
TI  - Epileptic seizure detection - an AR model based algorithm for implantable device.
AB  - The algorithm of epileptic seizure is at the core of any implantable device aimed
      to treat the symptoms of this disorder. A training free (on line) epileptic
      seizure detection algorithm for implantable device utilizing Autoregressive (AR)
      model parameters is developed and studied. Pre-recorded (off line) epileptic
      seizure data are used to estimate the internal parameters of an AR model prior
      and following the seizure Principle Component Analysis (PCA) is used for reducing
      the dimension of the problem while allowing only the salient features
      representing the seizure onset to be saved into the implantable device. The
      implantable device estimates the AR model parameter in real time and compares the
      saved features of seizure onset with feature from the incoming signals using
      cosine similarity. In order to guarantee an efficient on line signal processing,
      Weighted Least Square Estimation (WLSE) model is utilized. Simulation result
      shows that the proposed method has average 96.6% detection accuracy and 1.2ms
      latency for the data sets under study. The proposed approach can be extended to
      multi channel approach using Multi-Variant Autoregressive (MVAR) model which
      enables seizure foci localization and the sophisticated seizure prediction.

PMID- 21096474
TI  - A novel morphology-based classifier for automatic detection of epileptic
      seizures.
AB  - Most of the automatic seizure detection schemes reported in the literature are
      complex for detecting seizures that are of (a) short duration, (b) minimal
      amplitude evolution, or (c) non-rhythmic mixed frequency epileptic activity. We
      present a novel morphology-based classifier to detect epileptic seizures for
      intracranial EEG recording. The method characterizes epileptic seizure by
      detecting continual presence of sharp half-waves in the EEG. Performance is
      evaluated on single channel intracranial EEG of seven patients, and compared to
      two previously developed methods for intracranial EEG recordings by our research
      group. The method detects seizure of varying types (rhythmic, non-rhythmic, short
      and long- seizures) with a sensitivity of 100%, a false detection rate of 0.1/h
      and an average onset delay of 9.1 s. The method outperforms the two previously
      developed methods and is computationally simple for real-time application.
      Preliminary results on seven patients data are very promising.

PMID- 21096475
TI  - Clinical study of neurorehabilitation in stroke using EEG-based motor imagery
      brain-computer interface with robotic feedback.
AB  - This clinical study investigates the ability of hemiparetic stroke patients in
      operating EEG-based motor imagery brain-computer interface (MI-BCI). It also
      assesses the efficacy in motor improvements on the stroke-affected upper limb
      using EEG-based MI-BCI with robotic feedback neurorehabilitation compared to
      robotic rehabilitation that delivers movement therapy. 54 hemiparetic stroke
      patients with mean age of 51.8 and baseline Fugl-Meyer Assessment (FMA) 14.9 (out
      of 66, higher = better) were recruited. Results showed that 48 subjects (89%)
      operated EEG-based MI-BCI better than at chance level, and their ability to
      operate EEG-based MI-BCI is not correlated to their baseline FMA (r=0.358). Those
      subjects who gave consent are randomly assigned to each group (N=11 and 14) for
      12 1-hour rehabilitation sessions for 4 weeks. Significant gains in FMA scores
      were observed in both groups at post-rehabilitation (4.5, 6.2; p=0.032, 0.003)
      and 2-month post-rehabilitation (5.3, 7.3; p=0.020, 0.013), but no significant
      differences were observed between groups (p=0.512, 0.550). Hence, this study
      showed evidences that a majority of hemiparetic stroke patients can operate EEG
      based MI-BCI, and that EEG-based MI-BCI with robotic feedback neurorehabilitation
      is effective in restoring upper extremities motor function in stroke.

PMID- 21096476
TI  - A neural repair treatment with gait training improves motor function recovery
      after spinal cord injury.
AB  - Aimed to develop an effective approach for treating spinal cord injury (SCI), we
      investigated the effectiveness of a treatment strategy that combined peripheral
      nerve grafting, nerve growth factors and functional task based physical therapy
      on non-human primate models. SCI was by unilateral surgical hemi-section at the
      T8 spine level (approximately 4 mm gap). Two of the 4 subjects as treatment
      received the transplants of sural nerve segments as well as infused acidic
      fibroblast growth factor (aFGF) to the injured spinal cord. All four subjects
      received physical therapy and bipedal walking training on a treadmill to promote
      motor function recovery. A comprehensive evaluation system including general
      observation in the home cage, behavioral test and clinic score system was used to
      assess the effect of the treatment. The recovery of functional mobility in
      treated group is much faster than the control group. The treated group started to
      move around in their cages within a week and continued to improve in walking
      performance as measured by gait symmetry, while the control group developed
      spasticity and rigidity with a much slower and less functional recovery of
      mobility. All these results suggest that the treatment strategy of peripheral
      nerve grafting with aFGF combined with physical therapy is effective to treat
      SCI.

PMID- 21096477
TI  - Small bowel tumors detection in capsule endoscopy by Gaussian modeling of color
      curvelet covariance coefficients.
AB  - This paper is concerned with the classification of tumoral tissue in the small
      bowel by using capsule endoscopic images. The followed approach is based on
      texture classification. Texture descriptors are derived from selected scales of
      the Discrete Curvelet Transform (DCT). The goal is to take advantage of the high
      directional sensitivity of the DCT (16 directions) when compared with the
      Discrete Wavelet Transform (DWT) (3 directions). Second order statistics are then
      computed in the HSV color space and named Color Curvelet Covariance (3C)
      coefficients. Finally, these coefficients are modeled by a Gaussian Mixture Model
      (GMM). Sensitivity of 99% and specificity of 95.19% are obtained in the testing
      set.

PMID- 21096478
TI  - Boosting instance prototypes to detect local dermoscopic features.
AB  - Local dermoscopic features are useful in many dermoscopic criteria for skin
      cancer detection. We address the problem of detecting local dermoscopic features
      from epiluminescence (ELM) microscopy skin lesion images. We formulate the
      recognition of local dermoscopic features as a multi-instance learning (MIL)
      problem. We employ the method of diverse density (DD) and evidence confidence
      (EC) function to convert MIL to a single-instance learning (SIL) problem. We
      apply Adaboost to improve the classification performance with support vector
      machines (SVMs) as the base classifier. We also propose to boost the selection of
      instance prototypes through changing the data weights in the DD function. We
      validate the methods on detecting ten local dermoscopic features from a dataset
      with 360 images. We compare the performance of the MIL approach, its boosting
      version, and a baseline method without using MIL. Our results show that boosting
      can provide performance improvement compared to the other two methods.

PMID- 21096479
TI  - Classification of apoptosis using advanced clustering techniques on digital
      microscopic images.
AB  - Programmed cell death, also known as apoptosis is of fundamental importance in
      many biological processes and also highly associated with serious diseases like
      cancer and HIV. The current paper presents an innovative method for apoptosis
      phenomenon characterization based on apoptotic cell quantification and detection
      using active contours. Subsequently, we employ appropriate data mining techniques
      and perform characterization of apoptosis on digital microscopic images. A
      particular class of clustering algorithms, utilizing information driven by the
      Principal Component Analysis, has been very successful in dealing with such data.
      In this work, we employ a recently proposed clustering algorithm to solve this
      real world clustering task.

PMID- 21096480
TI  - Recognizing physical activity from ego-motion of a camera.
AB  - A new image based activity recognition method for a person wearing a video camera
      below the neck is presented in this paper. The wearable device is used to capture
      video data in front of the wearer. Although the wearer never appears in the
      video, his or her physical activity is analyzed and recognized using the recorded
      scene changes resulting from the motion of the wearer. Correspondence features
      are extracted from adjacent frames and inaccurate matches are removed based on a
      set of constraints imposed by the camera model. Motion histograms are defined and
      calculated within a frame and we define a new feature called accumulated motion
      distribution derived from motion statistics in each frame. A Support Vector
      Machine (SVM) classifier is trained with this feature and used to classify
      physical activities in different scenes. Our results show that different types of
      activities can be recognized in low resolution, field acquired real-world video.

PMID- 21096481
TI  - Parallel nonlinear analysis of weighted brain's gray and white matter images for
      Alzheimer's dementia diagnosis.
AB  - In this study, we are proposing a novel nonlinear classification approach to
      discriminate between Alzheimer's Disease (AD) and a control group using T1
      weighted and T2-weighted Magnetic Resonance Images (MRI's) of brain. Since T1
      weighted images and T2-weighted images have inherent physical differences,
      obviously each of them has its own particular medical data and hence, we
      extracted some specific features from each. Then the variations of the relevant
      eigenvalues of the extracted features were tracked to pick up the most
      informative ones. The final features were assigned to two parallel systems to be
      nonlinearly categorized. Considering the fact that AD defects the white and gray
      regions of brain more than its black and marginal regions, and also since T1
      weighted has more medical data of white and gray regions than T2-weighted images,
      we put optimal weights for the two outputs. Combination of these two results made
      the final decision of AD diagnosis system. The dataset includes 60 T1-weighted
      images and 60 T2-weighted images of normal and abnormal cases. The dataset which
      includes different cross-sections of the brain, after an accurate registration,
      was split to two groups of test set (40 percent of the dataset) and training set
      (60 percent of the dataset). The results demonstrate more than two thirds of
      accuracy in detection of normal and abnormal images.

PMID- 21096482
TI  - Computer-aided diagnosis of breast cancer from magnetic resonance imaging
      examinations by custom radial basis function vector machine.
AB  - This paper presents a new method for performing supervised learning
      (classification) and demonstrates the technique by applying it to the detection
      of breast cancer from the dynamic information obtained in magnetic resonance
      imaging examinations. The proposed method is a vector machine similar to the
      established support vector machine (SVM) method, however, our method involves a
      reformulation of the classification/prediction process. The proposed
      classification methodology is compared with the SVM, with both methods using the
      established radial basis function kernel. The proposed vector machine formulation
      applies test biasing in a new manner and is demonstrated to produce robust
      solutions as measured by the receiver operating characteristic (ROC) curve area.
      The technique is compared with SVMs and yields test improvements up to an
      additional 9.8% sensitivity or 7.2% specificity.

PMID- 21096483
TI  - A preliminary study of moment-based texture analysis for medical images.
AB  - A moment-based approach is proposed for texture analysis of medical images. The
      neighborhood of texture pixel is calculated by moments for texture feature
      extraction. After verified on Brodatz textures, the moment-based texture analysis
      method is applied on CT liver scan classification and prostate ultrasound
      segmentation. A support vector machine and a multi-channel active contour model
      are used in our application. The result shows that our method works well but
      still have some limitations.

PMID- 21096484
TI  - SVM based colon polyps classifier in a wireless active stereo endoscope.
AB  - This work focuses on the recognition of three-dimensional colon polyps captured
      by an active stereo vision sensor. The detection algorithm consists of SVM
      classifier trained on robust feature descriptors. The study is related to
      Cyclope, this prototype sensor allows real time 3D object reconstruction and
      continues to be optimized technically to improve its classification task by
      differentiation between hyperplastic and adenomatous polyps. Experimental results
      were encouraging and show correct classification rate of approximately 97%. The
      work contains detailed statistics about the detection rate and the computing
      complexity. Inspired by intensity histogram, the work shows a new approach that
      extracts a set of features based on depth histogram and combines stereo
      measurement with SVM classifiers to correctly classify benign and malignant
      polyps.

PMID- 21096485
TI  - Curvatures with uncertainties derived in conformal space to characterize tendon
      microstructure.
AB  - There is a growing demand for non-invasive methods to diagnose tendon injuries
      and monitor the healing processes of their repair. To date there is limited
      knowledge on their structure and function and the interlink between these. One of
      the potential targets in this investigation is the extracellular matrix (ECM)
      that captures its structural changes. Recently we reported on the assessment
      tendon damage on a macroscopic level from high field MR signals. In this paper,
      we present a methodology that enables structural description on a microscopic
      level. We derived curvature values from the conformal monogenic signal, which
      however can become unreliable in the presence of noise. To account for this we
      use non parametric noise properties and a 1D feature based uncertainty measure in
      an iterative framework using Hidden Markov Measure Field (HMMF). The proposed
      method reveals that curvature values derived from normal tendon tissue microscopy
      images are higher and more homogenous than curvature values derived from the
      damaged tendon images.

PMID- 21096486
TI  - Using PCA and LVQ neural network for automatic recognition of five types of white
      blood cells.
AB  - Designing an effective classifier has been a challenging task in the previous
      methods proposed in the literature. In this paper, we apply a combination of
      feature selection algorithm and neural network classifier in order to recognize
      five types of white blood cells in the peripheral blood. For this purpose, first
      nucleus and cytoplasm are segmented using Gram-Schmidt method and snake
      algorithm, respectively; second, three kinds of features are extracted from the
      segmented areas. Then the best features are selected using Principal Component
      Analysis (PCA). Finally, five types of white blood cells are classified using
      Learning Vector Quantization (LVQ) neural network. The performance analysis of
      the proposed algorithm is validated by an expert's classification results. The
      efficiency of the proposed algorithm is highlighted by comparing our results with
      those reported in a recent article which proposed a method based on the
      combination of Sequential Forward Selection (SFS) as the feature selection
      algorithm and Support Vector Machines (SVM) as the classifier.

PMID- 21096487
TI  - Genetic algorithm and image processing for osteoporosis diagnosis.
AB  - Osteoporosis is considered as a major public health threat. It is characterized
      by a decrease in the density of bone, decreasing its strength and leading to an
      increased risk of fracture. In this work, the morphological, topological and
      mechanical characteristics of 2 populations of arthritic and osteoporotic
      trabecular bone samples are evaluated using artificial intelligence and recently
      developed skeletonization algorithms. Results show that genetic algorithms
      associated with image processing tools can precisely separate the 2 populations.

PMID- 21096488
TI  - Automatic learning of spatial patterns for diagnosis of skin lesions.
AB  - We present a technique for automatic diagnosis of malignant melanoma based
      exclusively on local pattern analysis. The technique relies on local binary
      patterns in small sections in the image, and automatically selects the relevant
      texture features from those that discriminate best between benign and malignant
      skin lesions. The classification is performed using support vector machines, and
      the feature vectors are clustered using K-means clustering. The effects of K and
      window size are investigated. Reported average specificity and sensitivity are
      73% for optimal parameter choice, indicating that the procedure is a useful part
      of a diagnostic system.

PMID- 21096489
TI  - Registration of 2D point sets by complex translation and rotation operations.
AB  - Alignment of two sets containing two dimensional vectors (2D points) constitutes
      an important problem in medical imaging, remote sensing, and computer vision. We
      assume that the points in one set, called the transformed set, are constructed by
      translating and rotating the points in the other set, called the original set.
      The points in both sets are represented by complex numbers. In order to translate
      and then rotate a point, we add a complex constant and then multiply by a complex
      exponential respectively. We construct a cost function which tries to achieve the
      least-squares differences between a given transformed set and the set containing
      transformed points with respect to optimization parameters. We implement the
      Newton-Raphson optimization algorithm with polynomial line search in order to
      minimize this cost function. Simulation results with multiple datasets
      demonstrate that the proposed method aligns two sets efficiently and reliably.

PMID- 21096490
TI  - A semi-automatic method for positioning a femoral bone reconstruction for strict
      view generation.
AB  - In this paper we present a semi-automatic method for femoral bone positioning
      after 3D image reconstruction from Computed Tomography images. This serves as
      grounding for the definition of strict axial, longitudinal and anterior-posterior
      views, overcoming the problem of patient positioning biases in 2D femoral bone
      measuring methods. After the bone reconstruction is aligned to a standard
      reference frame, new tomographic slices can be generated, on which unbiased
      measures may be taken. This could allow not only accurate inter-patient
      comparisons but also intra-patient comparisons, i.e., comparisons of images of
      the same patient taken at different times. This method could enable medical
      doctors to diagnose and follow up several bone deformities more easily.

PMID- 21096491
TI  - Pre-reconstruction rigid body registration for positron emission tomography: an
      initial validation against ground truth.
AB  - Our recent adaptation to PET of the method of Fitchard et al. [1], [2], [3] for
      rigid body registration of CT sinograms enables motion between two temporal
      frames of PET data to be estimated and corrected prior to reconstruction. This
      avoids both the computation required by multiple reconstructions and the need to
      make choices regarding reconstruction methods that influence the images produced,
      and potentially change the estimated motion. Using realistic, simulated data with
      known ground truth, we report an initial investigation into the performance of
      the method as the number of counts and the accuracy with which the scan is
      divided into frames, corresponding to different positions, varies.

PMID- 21096492
TI  - Multimodal target correction by local bone registration: a PET/CT evaluation.
AB  - PET/CT guidance for percutaneous interventions allows biopsy of suspicious
      metabolically active bone lesions even when no morphological correlation is
      delineable in the CT images. Clinical use of PET/CT guidance with conventional
      step-by-step technique is time consuming and complicated especially in cases in
      which the target lesion is not shown in the CT image. Our recently developed
      multimodal instrument guidance system (IGS) for PET/CT improved this situation.
      Nevertheless, bone biopsies even with IGS have a trade-off between precision and
      intervention duration which is proportional to patient and personnel exposure to
      radiation. As image acquisition and reconstruction of PET may take up to 10
      minutes, preferably only one time consuming combined PET/CT acquisition should be
      needed during an intervention. In case of required additional control images in
      order to check for possible patient movements/deformations, or to verify the
      final needle position in the target, only fast CT acquisitions should be
      performed. However, for precise instrument guidance accounting for patient
      movement and/or deformation without having a control PET image, it is essential
      to be able to transfer the position of the target as identified in the original
      PET/CT to a changed situation as shown in the control CT.

PMID- 21096493
TI  - Postoperative evaluation of surgery for craniosynostosis based on image
      registration techniques.
AB  - Craniosynostosis consists of a premature fusion of the sutures in an infant
      skull, which restricts the skull and brain growth. During the last decades there
      has been a rapid increase of fundamentally diverse surgical treatment methods. At
      present, the surgical outcome has been assessed using global variables such as
      cephalic index, head circumerence and intracranial volume. However, the variables
      have failed in describing the local deformations and morphological changes, which
      are proposed to more likely induce neurological disorders.

PMID- 21096494
TI  - A bio-analytical system for rapid cellular electrophysiological assays.
AB  - In this paper, the use of non-uniform ac electric fields on biological cells for
      bioanalysis, through multiple, independently configurable channels is presented.
      The programmable system has been used to obtain the dielectrophoretic spectra of
      cells in near real time, within 90 seconds. This is a significant improvement on
      existing dielectrophoretic techniques as simultaneous parallel measurement of the
      dielectrophoretic forces at different frequencies has potential of revealing
      subtle changes to the electrophysiology of cells, as they occur. The results show
      that with continuous on-chip monitoring, cells exposed to a chemical agent that
      induces apoptosis begin to exhibit a spectrum that differs from untreated cells,
      as indicated from shifts in the observed crossover frequency values.

PMID- 21096495
TI  - Integrated fluidic system for bio-molecule separation.
AB  - An integrated fluidic system has been fabricated, capable of separating a mixture
      of different bio-molecules into its components. It is composed of a filter and an
      actuator; the pressure generated by the actuator sustains the flow of the mixture
      through the filter. The actuator is made by stacking several layers of conductive
      polymer. Actuator strain in excess of 10% has been obtained, which corresponds to
      a fluid flow of 3 microL/min in the fabricated system. The filter consists of an
      ordered array of Si micro-pillars. A mixture composed of DNA fragments of
      different length (300 and 400 base-pair) has been effectively separated by using
      the fabricated filter and chromatographic techniques.

PMID- 21096496
TI  - Rapid monodisperse microencapsulation of single cells.
AB  - A microfluidic device was designed having the ability to continuously produce
      monodisperse microcapsules with controlled cell loading. The design included
      stages of inertial focusing, droplet generation, and photopolymerization.
      Prototype microfluidic devices were fabricated in polydimethylsiloxane (PDMS) to
      demonstrate each stage using poly(ethylene-glycol)-diacrylate (PEGDA) as the
      encapsulating material and oil as the droplet-containing medium, creating a water
      in-oil emulsion. 10.3-um-diameter fluorescent polystyrene beads were used as cell
      simulants. In the first stage, inertial focusing was demonstrated using a
      straight-channel configuration. In the second stage, droplets with a 60+/-5um
      diameter were generated. In the third stage, successful encapsulation of the
      beads in hydrogel droplets was verified. This technology can significantly impact
      a wide research area ranging from cellular therapeutics to single-cell
      manipulation.

PMID- 21096497
TI  - Fully integrated micro-separator with soft-magnetic micro-pillar arrays for
      filtrating lymphocytes.
AB  - A fully integrated micro-separator with soft-magnetic micro-pillar arrays has
      been developed, which merely employs one independent Lab-On-Chip to realize the
      lymphocytes isolation from the human whole blood. The simulation, fabrication and
      experiment are executed to realize this novel microseparator. The simulation
      results show that, the soft-magnetic micro-pillars array can amplify and
      redistribute the electromagnetic field generated by the microcoils. The tests
      certify desirable separation efficiency can be realized using this new separator
      at low current. No extra cooling system is required for such a micro-separator.
      This micro-separator can also be used to separate other target cells or particles
      with the same principle.

PMID- 21096498
TI  - Direct Analog-to-QRS detection front-end architecture for wearable ECG
      applications.
AB  - The aim of this paper is to demonstrate a highly integrated architecture for
      direct Analog-to-QRS detection for ultra low power single chip implementation
      suitable for long term wearable monitoring. A novel variable input-feature
      correlated asynchronous sampling technique is proposed for direct sampling-cum
      data compression at the ECG electrodes with embedded mixed-signal algorithm for
      direct recognition and capture of the fiducial points of the ECG signal, to
      indicate the occurrence of the Q, R and S waves. Simulation results show two key
      advantages (a) large compression at the source and (b) direct analog to
      information conversion with 98% accuracy of detection, with extremely low power
      and storage requirements.

PMID- 21096499
TI  - An asymmetric resonant coupling wireless power transmission link for Micro-Ball
      Endoscopy.
AB  - This paper investigates the design and optimization of a wireless power
      transmission link targeting Micro-Ball Endoscopy applications. A novel asymmetric
      resonant coupling structure is proposed to deliver power to an endoscopic Micro
      Ball system for image read-out after it is excreted. Such a technology enables
      many key medical applications with stringent requirements for small system volume
      and high power delivery efficiency. A prototyping power transmission sub-system
      of the Micro-Ball system was implemented. It consists of primary coil, middle
      resonant coil, and cube-like full-direction secondary receiving coils. Our
      experimental results proved that 200mW of power can be successfully delivered.
      Such a wireless power transmission capability could satisfy the requirements of
      the Micro-Ball based endoscopy application. The transmission efficiency is in the
      range of 41% (worst working condition) to 53% (best working condition). Comparing
      to conventional structures, Asymmetric Resonant Coupling Structure improves power
      efficiency by 13%.

PMID- 21096500
TI  - 3-D modeling of a carbon nanotube cantilever biosensor.
AB  - In this paper, 3-D finite element modeling and simulations are carried out to
      investigate the bending deformation of a single-walled carbon nanotube cantilever
      biosensor due to mass attached, and addition of a nano-scale particles to the
      beam tip resulting from the bioparticle detection. In addition, an algorithm for
      an electrostatic-mechanical coupled system is developed. The computed results are
      in excellent agreement with the well known electrostatic equations that govern
      the deformation.

PMID- 21096501
TI  - A capacitive ECG array with visual patient feedback.
AB  - Capacitive electrocardiogram (ECG) sensing is a promising technique for less
      constraining vital signal measurement and close to a commercial application. Even
      bigger trials testing the diagnostic significance were already done with single
      lead systems. Anyway, most applications to be found in research are limited to
      one channel and thus limited in its diagnostic relevance as only diseases coming
      along with a change of the heart rate can be diagnosed adequately. As a
      consequence the need for capacitive multi-channel ECGs combining the diagnostic
      relevance and the advantages of capacitive ECG sensing emerges. This paper
      introduces a capacitive ECG measurement system which allows the recording of
      standardized ECG leads according to Einthoven and Goldberger by means of an
      electrode array with nine electrodes.

PMID- 21096502
TI  - BioTones: a wearable device for EMG auditory biofeedback.
AB  - In this paper, we introduce a novel technology to convert bioelectrical signals
      into sound and its application in biofeedback. The surface electromyogram is
      adopted as the bioelectrical signal and converted into an auditory signal. The
      sound conversion occurs inside a wearable device. In general, visual feedback can
      provide more information than acoustic feedback, however, we assume that the
      latter can represent bioelectrical signals as well as the visual medium. We have
      been investigating auditory conversion methods and analyze how they were
      perceived by several subjects. We also investigated the auditory ability of
      humans from an acousticopsychological point of view. According to the results of
      this examination, the acoustic sense has the ability to gather enough information
      to cognize the bioelectrical signal. Another important point we analyzed was
      whether a conversion algorithm should map multiple bioelectrical signals into
      sounds signals at once or sequentially.

PMID- 21096503
TI  - An electronic DNA sensor chip using integrated capacitive read-out circuit.
AB  - This paper presents fully integrated label-free DNA recognition circuit based on
      capacitance measurement. A CMOS-based DNA sensor is implemented for the
      electrical detection of DNA hybridization. The proposed architecture detects the
      difference of capacitance through the integration of current mismatch of
      capacitance between reference electrodes functionalized with only single-stranded
      DNA and sensing electrodes bound with complementary DNA strands specifically. In
      addition, to minimize the effects of parallel resistance between electrodes and
      DNA layers, the compensation technique of leakage current through the use of
      constant current charging and discharging is implemented in the proposed
      detection circuit. The chip was fabricated in 0.35um 4-metal 2-poly CMOS process,
      and 16 * 8 sensing electrode arrays were fabricated by post-processing steps.

PMID- 21096504
TI  - A fractional electrical impedance model in detection of occlusal non-cavitated
      carious.
AB  - Identification of occlusal caries remains a major concern for the diagnosis,
      which is still highly subjective and presents a considerable variability among
      clinicians. Dentists have been observed an increase of a specifically type of
      caries lesion, the hidden caries. Among the available techniques to assess the
      hidden caries, the measurement of electrical impedance has been shown to be one
      of the most promising. This paper presents a fractional electrical model for the
      tooth and uses such a model associated to a BioImpedance Spectroscopy (BIS)
      method based on the current response to a step voltage excitation. An analytical
      solution for the current response is presented based on a fractional calculus
      approach. Estimate parameters of the proposed model achieved using an in vitro
      data acquired in a protocol performed to collect bioimpedance data showed that it
      seems possible to detect occlusal non-cavitated caries, and that the principal
      confounding factor in the diagnosis of the incipient occlusal caries, the
      pigmented areas, can also be differentiated.

PMID- 21096505
TI  - Bioimpedance monitoring for cryopreservation process control.
AB  - This paper analyses the use of Electrical Impedance Spectroscopy (EIS) to
      efficiently monitor cryoprotectant concentrations in cryopreservation protocols.
      The proposed technique can improve methods such as Liquidus Tracking (LT),
      allowing vitrification without exposing tissues to damaging concentrations of
      cryoprotectant at relatively high temperatures, and avoiding rapid temperature
      changes. This work is focused to continuous monitoring of cryoprotectant
      concentrations by detecting changes in electrical impedance. These variations,
      derived from cryoprotectant perfusion inside cells and tissues, can be
      efficiently measure by using of EIS. Finite element simulation performed with
      COMSOL Multiphysics software was used to analyse the frequency response of a two
      electrode system to several concentrations of Me2SO, perfused into 3T3
      fibroblasts and monolayers of Mesenchymal Stem Cells (MSCs), fundamental in
      tissue-based therapeutics.

PMID- 21096506
TI  - A digital driven right leg circuit.
AB  - A novel scheme and a digital approach to the Driven Right Leg Circuit (DRL) are
      presented. It presents an ultra high common mode (CM) reduction of power line
      interference (higher than 80dB) without endangering stability. This improves by
      40-50dB the CM reduction provided by a classical analog DRL, retaining the same
      stability criterion. The improvement comes from the inclusion of a high Q
      resonator in parallel with the common mode amplifier. It provides a large gain at
      power line frequency (50/60 Hz) whereas it does not significantly affect the open
      loop gain for high frequencies. The proposed scheme can be thought as an analog
      circuit, but the accuracy required, mainly in the resonator frequency response,
      leads to a digital implementation. In this way, component ageing and thermal
      fluctuation problems are avoided, as well as the need for manual adjusting. A
      prototype of the proposed DRL circuit was built and tested in laboratory
      conditions showing an open-loop gain of 74dB at 50Hz. It was also tested by
      acquiring real EEG signals.

PMID- 21096507
TI  - Hook effect correction & resistance-based cole fitting prior cole model-based
      analysis: experimental validation.
AB  - The analysis of measurements of Electrical Bioimpedance (EBI) is on the increase
      for performing non-invasive assessment of health status and monitoring of
      pathophysiological mechanisms. EBI measurements might contain measurements
      artefacts that must be carefully removed prior to any further analysis. Cole
      model-based analysis is often selected when analysing EBI data and might lead to
      miss-conclusion if it is applied on data contaminated with measurement artefacts.
      The recently proposed Correction Function to eliminate the influence of the Hook
      Effect from EBI data and the fitting to the real part of the Cole model to
      extract the Cole parameters have been validated on experimental measurements. The
      obtained results confirm the feasible experimental use of these promising pre
      processing tools that might improve the outcome of EBI applications using Cole
      model-based analysis.

PMID- 21096508
TI  - Sliding-window motion artifact rejection for Functional Near-Infrared
      Spectroscopy.
AB  - Functional Near-Infrared Spectroscopy (fNIR) is an optical brain monitoring
      technology that tracks changes in hemodynamic responses within the cortex. fNIR
      uses specific wavelengths of light, introduced at the scalp, to enable the
      noninvasive measurement of changes in the relative ratios of deoxygenated
      hemoglobin (deoxy-Hb) and oxygenated hemoglobin (oxy-Hb) during brain activity.
      This technology allows the design of portable, safe, affordable, noninvasive, and
      minimally intrusive monitoring systems that can be used to measure brain activity
      in natural environments, ambulatory and field conditions. However, for such
      applications fNIR signals can get prone to noise due to motion of the head.
      Improving signal quality and reducing noise, can be especially challenging for
      real time applications. Here, we study motion artifact related noise especially
      due to poor and changing sensor coupling. We have developed a simple and
      iterative method that can be used to automate the preprocessing of data to
      identify segments with such noise for exclusion and this method is also suitable
      for real time applications.

PMID- 21096509
TI  - Extraction of M and P components from the visual evoked potential using
      pseudorandom stimulation with swept parameter technique.
AB  - To develop a method of extract magnocellular (M) and parvocellular (P) components
      from VEP, the nonlinear system identification method using pseudorandom binary
      sequence (PRBS) stimulation combined with swept parameter technique was examined.
      VEP elicited by achromatic sinusoidal grating reverse based on PRBS was recorded
      and their binary kernels were calculated as cross-correlation between PRBS and
      VEP. To manipulate the magnitudes of M and P visual pathways responses in VEP,
      the spatial frequency of gratings were swept during the PRBS stimulation. VEP to
      this stimulation was recorded from 4 healthy participants and their binary
      kernels changes during the stimulation were evaluated. PRBS stimulation of 40950
      ms period was repeated twice, and the spatial frequency was swept from 0.5 to 9
      [c/d] or 9 to 0.5 [c/d] within the period. Binary kernel of each epoch was
      calculated by cross-correlating VEP with PRBS of 40950 ms duration. Different
      waveforms of binary kernels obtained from the former and latter half of the PRBS
      stimulation were confirmed, and the waveforms were continuously changed during
      the stimulation. The changes may reflect the M and P pathway contribution changes
      during the stimulation and depend on the spatial frequency sweeping. The
      suggested technique would be effective for studying and screening several eye and
      neurocognitive disorders which have been reported to relate with selective damage
      in M/P pathways.

PMID- 21096510
TI  - MEG brain activities reflecting affection for visual food stimuli.
AB  - This study aimed to explore the modulation of alpha rhythm in response to food
      pictures with distinct affection values. We examined the method to discriminate
      subject's state, i.e., whether he/she liked the article of food or not, from MEG
      signals detected over the head. Pictures of familiar foods were used as affective
      stimuli, while those pictures with complementary color phase were used as non
      affective stimuli. Alpha band signals in a narrow frequency window around the
      spectral peak of individual subjects were wavelet analyzed and phase-locked
      component to the stimulus onset was obtained as a complex number. The amplitude
      of the phase-locked component was averaged during 0-1 s after stimulus onset for
      30 epochs in a measurement session and across 76 channels of MEG sensor. In
      statistical test of individual subjects, significant difference was found in the
      real part of the averaged phase-locked amplitude between the normal-color and
      reverse-color pictures. These results suggest that affective information
      processing of food pictures is reflected in the synchronized component of narrow
      band alpha rhythm.

PMID- 21096511
TI  - Time change of perceptual reversal of ambiguous figures by rTMS.
AB  - The aim of this study was to investigate the effect of stimulus frequency and
      number of pulses during rTMS (repetitive transcranial magnetic stimulation) on
      the phenomenon of perceptual reversal. Particularly, we focused on the temporal
      dynamics of perceptual reversal in the right SPL (superior parietal lobule),
      using the spinning wheel illusion. We measured the IRT (inter-reversal time) of
      perceptual reversal. To investigate whether stimulus frequency or the number of
      pulses is critical for the rTMS effect, we applied the following schedules over
      the right SPL and the right PTL (posterior temporal lobe): 0.25Hz 60 pulses,
      0.25Hz 120pulses, 0.5Hz 120 pulses, and 1Hz 120 pulses biphasic rTMS at 90% of
      the resting motor threshold. As a control, we included a No-TMS condition. The
      results showed that rTMS with 0.25Hz 60 pulses over the right SPL caused shorter
      IRT. There were no significant differences between IRTs for rTMS with 0.25Hz 120
      pulses, 0.5Hz 120 pulses or 1Hz 120 pulses over the right SPL. Comparing these
      results with those of a previous study, we found that an rTMS condition with 60
      pulses causes shorter IRT; 240 pulses causes longer IRT; and 120 pulses does not
      change IRT. Therefore, when applying rTMS over the right SPL, the IRT of
      perceptual reversal is primarily affected by the number of pulses.

PMID- 21096512
TI  - An experimental study on target recognition using white canes.
AB  - To understand basic tactile perception using white canes, we compared tapping
      (two times) and pushing (two times) methods using the index finger and using a
      white cane, with and without accompanying auditory information. Participants were
      six visually impaired individuals who used a white cane to walk independently in
      their daily lives. For each of the tapping and pushing and sound or no sound
      conditions, participants gave magnitude estimates for the hardness of rubber
      panels. Results indicated that using a white cane produces sensitivity levels
      equal to using a finger when accompanied by auditory information, and suggested
      that when using a white cane to estimate the hardness of a target, it is most
      effective to have two different modalities of tactile and auditory information
      derived from tapping.

PMID- 21096513
TI  - Off-line and on-line vigilance estimation based on linear dynamical system and
      manifold learning.
AB  - For many human machine interaction systems, to ensure work safety, the techniques
      for continuously estimating the vigilance of operators are highly desirable. Up
      to now, various methods based on electroencephalogram (EEG) are proposed to solve
      this problem. However, most of them are static methods and are based on
      supervised learning strategy. The main deficiencies of the existing methods are
      that the label information is hard to get and the time dependency of vigilance
      changes are ignored. In this paper, we introduce the dynamic characteristics of
      vigilance changes into vigilance estimation and propose a novel model based on
      linear dynamical system and manifold learning techniques to implement off-line
      and online vigilance estimation. In this model, both spatial information of EEG
      and temporal information of vigilance changes are used. The label information
      what we need is merely to know which EEG indices are important for vigilance
      estimation. Experimental results show that the mean off-line and on-line
      correlation coefficients between estimated vigilance level and local error rate
      in second-scale without being averaged are 0.89 and 0.83, respectively.

PMID- 21096514
TI  - Vigilance estimation by using electrooculographic features.
AB  - This study aims at using electrooculographic (EOG) features, mainly slow eye
      movements (SEM), to estimate the human vigilance changes during a monotonous
      task. In particular, SEMs are first automatically detected by a method based on
      discrete wavelet transform, then linear dynamic system is used to find the
      trajectory of vigilance changes according to the SEM proportion. The performance
      of this system is evaluated by the correlation coefficients between the final
      outputs and the local error rates of the subjects. The result suggests that SEMs
      perform better than rapid eye movements (REM) and blinks in estimating the
      vigilance. Using SEM alone, the correlation can achieve 0.75 for off-line, while
      combined with a feature from blinks it reaches 0.79.

PMID- 21096515
TI  - Towards an index of cognitive efficacy EEG-based estimation of cognitive load
      among individuals experiencing cancer-related cognitive decline.
AB  - This paper describes an effort to estimate variations in cognitive effort among
      cancer survivors experiencing treatment related cognitive decline. EEG-based
      cognitive state sensing algorithms were validated in the context of an experiment
      with 5 brain cancer and 5 breast cancer survivors. Workload was manipulated by
      varying text complexity and time pressure. Analysis indicates that EEG-based
      cognitive state sensing algorithms were able to distinguish between high and low
      cognitive workload with an average classification accuracy of 0.84. Results
      suggest that 5 to 10 channels of EEG can provide enough information to achieve
      classification accuracies exceeding 0.80. The highest density of informative
      sites were over the left temporal and mid to inferior frontal regions in the left
      hemisphere - regions that play a major role in language.

PMID- 21096516
TI  - Enhancing pilot performance with a SymBodic system.
AB  - Increased fatigue of pilots during long flights can place both humans and machine
      at high risk. In this paper, we describe our research on a SymBodic (SYMbiotic
      BODies) system designed to minimize pilot fatigue in a simulated 48 hour mission.
      The system detected the pilot's sleep breaks and used this information to plan
      future sleep breaks. When fatigue could not be prevented, the SymBodic system
      assisted the pilot by providing relevant flight information through a vibro
      tactile vest. Experiments showed that it was difficult for the pilot to adapt to
      the suggested sleep schedule within the duration of the experiment, and fatigue
      was not avoided. However, during periods of severe sleep deprivation, the
      SymBodic system significantly improved piloting performance.

PMID- 21096517
TI  - Assessment of observers' stability and reliability - a tool for evaluation of
      intra- and inter-concordance in animal behavioral recordings.
AB  - Behavior studies on the neurobiological effects of environmental, pharmacological
      and physiological manipulations in lab animals try to correlate these procedures
      with specific changes in animal behavior. Parameters such as duration, latency
      and frequency are assessed from the visually recorded sequences of behaviors, to
      distinguish changes due to manipulation. Since behavioral recording procedure is
      intrinsically interpretative, high variability in experimental results is
      expected and usual, due to observer-related influences such as experience,
      knowledge, stress, fatigue and personal biases. Here, we present a computer
      program that supports the assessment of inter- and intra-observer concordance,
      using statistical indices (e.g., Kappa and Kendal coefficients and concordance
      index). The software was tested in a case study with 4 different observers, naive
      to behavioral recording procedures. On paired analysis, the higher agreement
      index achieved was 0.76 (concordance index) and 0.47 (Kappa Coefficient, where 0
      is no agreement and 1 is total agreement). Observers showed poor concordance
      indices (lower than 0.7), emphasizing the concern on observer recording stability
      and on precise morphological definition of the recorded behaviors. These indices
      can also be used to train observers and to refine the behavioral catalogue
      definitions, as they are related to different behavioral recording aspects.

PMID- 21096518
TI  - Fuzzy-based simulation of real color blindness.
AB  - About 8% of men are affected by color blindness. That population is at a
      disadvantage since they cannot perceive a substantial amount of the visual
      information. This work presents two computational tools developed to assist color
      blind people. The first one tests color blindness and assess its severity. The
      second tool is based on Fuzzy Logic, and implements a method proposed to simulate
      real red and green color blindness in order to generate synthetic cases of color
      vision disturbance in a statistically significant amount. Our purpose is to
      develop correction tools and obtain a deeper understanding of the accessibility
      problems faced by people with chromatic visual impairment.

PMID- 21096519
TI  - Effects of additional workload on hand and tongue performance.
AB  - Tongue Drive System (TDS) is an unobtrusive, wireless, and wearable device that
      allows for real time tracking of the tongue motion in the oral space for
      communication, control, and navigation applications. Utilizing the TDS, we were
      able to assess the use of tongue motion as a voluntary motor modality and its
      effect on the human performance in a realistic environment. Preliminary human
      trials were conducted on 13 able-bodied subjects to assess the speed and accuracy
      of rapid repetitive goal-directed movements during independent or concurrent use
      of hand (index finger) and the tongue. The accuracy of hand and tongue movements
      was decreased with the concurrent hand and tongue task compared with the
      independent movement task. The speed of hand movement was also decreased with the
      concurrent hand and tongue movements, but not with the concurrent hand and
      cognitive task (arithmetic and memory). In contrast, the speed of tongue movement
      was maintained with the concurrent hand and tongue movements. Instead, the tongue
      speed was decreased with the concurrent tongue and cognitive task. It was
      suggested that control via tongue movement with TDS would have the advantage of
      maintaining comparable speeds between independent and concurrent use over the
      hand movement control during the tasks that require rapid repetitive goal
      directed movements.

PMID- 21096520
TI  - A software program for the head impulse testing device (HITD).
AB  - The vestibulo-ocular reflex (VOR) uses head angular acceleration information
      transduced by the semicircular canals in the inner ear in order to drive eye
      movements that compensate for head rotations, and thus stabilize the visual scene
      on the retina. Peripheral and central vestibular pathologies may impair the
      function of the VOR, so that compensation becomes incomplete, making clear vision
      during head movement impossible. Powerful adaptive mechanisms quickly allow the
      central nervous system to use residual vestibular information or information
      provided through other senses to supplement the deficient VOR. Such recovery
      makes the clinical diagnosis difficult to classical testing techniques, yet the
      head impulse test allows to reveal vestibular deficits even in adapted patients.
      A compensatory saccade at the end of the head movement is the clinical sign of a
      vestibular deficit, and may be spotted by the experienced clinician. Here we
      describe the rationale and the software program driving a new computerized
      technique for reliably assessing vestibular function at different head angular
      accelerations, based on evaluating the ability of the patient in reading a
      character on the screen while the head is being rotated.

PMID- 21096521
TI  - Optimized assessment of atrial fibrillation organization through suitable
      parameters of sample Entropy.
AB  - Sample Entropy (SampEn) is a nonlinear regularity index that requires the a
      priori selection of three parameters: the length of the sequences to be compared,
      m, the patterns similarity tolerance, r, and the number of samples under
      analysis, N. Appropriate values for m, r and N have been recommended in some
      cases, such as heart rate, hormonal data, etc., but no guidelines exist for the
      selection of that values. Hence, an optimal parameters study should be required
      for the application of SampEn to not previously analyzed biomedical signals. In
      this work, a thorough analysis on the optimal SampEn parameter values within two
      different scenarios of AF organization estimation, such as the prediction of
      paroxysmal AF termination and the electrical cardioversion outcome in persistent
      AF, is presented. Results indicated that, (i) the proportion between N and the
      sampling rate (f(s)) should be higher than one second and f(s) >= 256 Hz, (ii)
      overlapping between adjacent N-length windows does not improve organization
      estimation and (iii) values of m and r maximizing classification should be
      considered within a range wider than the proposed in the literature for heart
      rate analysis, i. e. m = 1 and m = 2 and r between 0.1 and 0.25 times the
      standard deviation of the data.

PMID- 21096522
TI  - Enhancement of atrial fibrillation electrical cardioversion procedures through
      the arrhythmia organization estimation from the ECG.
AB  - The development of non-invasive tools able to provide valuable information about
      the effectiveness of a shock in external electrical cardioversion (ECV) is
      clinically relevant to enhance these protocols in the treatment of atrial
      fibrillation (AF). The present contribution analyzes the ability of a non-linear
      regularity index, such as sample entropy (SampEn), to follow-up noninvasively AF
      organization under successive attempts of ECV and to predict the effectiveness of
      every single shock. Results showed that, after each unsuccessful shock, a SampEn
      relative decrease was observed for the patients who finally reverted to normal
      sinus rhythm (NSR), but the largest variation took place after the first attempt,
      thus indicating that this shock plays the most important role in the procedure.
      Indeed, by considering jointly the patients who needed only one shock and the
      patients who needed several shocks, 91.67% (22 out of 24) of ECVs resulting in
      NSR, 93.55% (29 out of 31) of ECVs relapsing to AF during the first month and
      100% (10 out of 10) of ECVs in which NSR was not restored were correctly
      classified. As conclusion, AF organization analysis via SampEn from the surface
      ECG can provide useful information that could improve the effectiveness of
      conventional external ECV protocols used in AF treatment.

PMID- 21096523
TI  - Towards natural non-invasive hand neuroprostheses for daily living.
AB  - In this paper we show how healthy subjects can operate a non-invasive
      asynchronous BCI for controlling a FES neuroprosthesis and manipulate objects to
      carry out daily tasks in ecological conditions. Both, experienced and novel
      subjects proved to be able to deliver mental commands with high accuracy and
      speed. Our neuroprosthetic approach relies on a natural interaction paradigm,
      where subjects delivers congruent MI commands (i.e., they imagining a movement of
      the same hand they control through FES). Furthermore, we have tested our approach
      in a common daily task such as handwriting, which requires the user to split
      his/her attention to multitask between BCI control, reaching, and the primary
      handwriting task itself. Interestingly, the very low number of erroneous trials
      illustrates how during the experiments subjects were able to deliver commands
      just when they intended to do so. Similarly, the subjects could perform actions
      while delivering, or preparing to deliver, mental commands.

PMID- 21096524
TI  - Connectivity mapping of the human ECoG during a motor task with a time-varying
      dynamic Bayesian network.
AB  - As a partially invasive and clinically obtained neural signal, the
      electrocorticogram (ECoG) provides a unique opportunity to study cortical
      processing in humans in vivo. Functional connectivity mapping based on the ECoG
      signal can provide insight into epileptogenic zones and putative cortical
      circuits. We describe the first application of time-varying dynamic Bayesian
      networks (TVDBN) to the ECoG signal for the identification and study of cortical
      circuits. Connectivity between motor areas as well as between sensory and motor
      areas preceding and during movement is described. We further apply the
      connectivity results of the TVDBN to a movement decoder, which achieves a
      correlation between actual and predicted hand movements of 0.68. This paper
      presents evidence that the connectivity information discovered with TVDBN is
      applicable to the design of an ECoG-based brain-machine interface.

PMID- 21096525
TI  - Network dynamics of the epileptic brain at rest.
AB  - Baseline neurodynamics are believed to play an important role in normal brain
      function. A potentially intrinsic property of the brain is the weak coupling
      between networks at rest, which enables it to be flexible, adapt, process novel
      stimuli, and learn. Brain regions become differentially coordinated in response
      to cognitive task and behavior demands and external stimuli. However, abnormally
      synchronized resting brain networks may also be associated with different
      pathologies. We investigated baseline network dynamics in the epileptic brain
      using information theoretic parameters to quantify coupling and directionality of
      information flow between different cortical regions. We estimated relative
      entropy, conditional mutual information and a related measure of directional
      coupling, from EEGs of patients with epilepsy and healthy subjects. At rest, the
      healthy brain appears to be characterized by low and non-directional network
      coupling, whereas the epileptic brain appears to be transiently and directionally
      synchronized.

PMID- 21096526
TI  - The central oscillatory network of essential tremor.
AB  - The responsible pathological mechanisms of essential tremor are not yet clear. In
      order to understand the mechanisms of the central network its sources need to be
      found. The cortical sources of both the basic and first "harmonic" frequency of
      essential tremor are addressed in this paper. The power and coherence were
      estimated using the multitaper method for EEG and EMG data from 6 essential
      tremor patients. The Dynamic Imaging of Coherent Sources (DICS) was used to find
      the coherent sources in the brain. Before hand this method was validated for the
      application of finding multiple sources for the same oscillation in the brain by
      using two model simulations which indicated the accuracy of the method. In all
      the essential tremor patients the corticomuscular coherence was also present in
      the basic and the first harmonic frequency of the tremor. The source for the
      basic frequency and the first harmonic frequency was in the region of primary
      sensory motor cortex, prefrontal and in the diencephalon on the contralateral
      side for all the patients. Thus the generation of these two oscillations involves
      the same cortical areas and indicates the oscillation at double the tremor
      frequency is a harmonic of the basic tremor frequency.

PMID- 21096527
TI  - Demand driven deep brain stimulation: regimes and autoregressive hidden Markov
      implementation.
AB  - Deep brain stimulation is an increasingly prevalent surgical option in the
      treatment of a multitude of neurological conditions, most notably Parkinson's
      disease. The development of a neurofeedback device is driven primarily by
      stimulator habituation, surgical risk factors, the cost of battery replacement,
      and reported neuropsychiatric side-effects under prolonged chronic
      administration. Here we present two distinct regimes for stimulation delivery in
      chronic and acute symptomatic conditions, presented in the context of
      Parkinsonian bradykinesias and tremor. Implementation strategies are discussed
      with a focus on vector-autoregressive hidden Markov models for tremor prediction.
      Detection of simple motor actions versus tremor are compared in a preliminary
      performance analysis.

PMID- 21096528
TI  - Detecting causal interdependence in simulated neural signals based on pairwise
      and multivariate analysis.
AB  - Our objective is to analyze EEG signals recorded with depth electrodes during
      seizures in patients with drug-resistant epilepsy. Usually, different phases are
      observed during the seizure process, including a fast onset activity (FOA). We
      aim to determine how cerebral structures get involved during this FOA, in
      particular whether some structure can "drive" some other structures. This paper
      focuses on a linear Granger causality based measure to detect causal relation of
      interdependence in multivariate signals generated by a physiology-based model of
      coupled neuronal populations. When coupling between signals exists, statistical
      analysis supports the relevance of this index for characterizing the information
      flow and its direction among neuronal populations.

PMID- 21096529
TI  - Stochastic resonance in connectivity between both auditory areas obtained by
      auditory stimuli.
AB  - We examined coherence of auditory steady state responses (ASSRs) in
      magnetoencephalogram to an ongoing sinusoidal amplitude modulated tone presented
      to the subject's left ear while bursts of white noise of various intensities were
      presented to the right ear. The results showed a significant enhancement in the
      real part of coherence of ASSRs obtained from the right and left temporal regions
      by the presence of white noise of appropriate intensity. The observed stochastic
      resonance (SR) most likely occurred within the central nervous system, which is
      from lateral superior olive to medial geniculate body. Our finding may be quite
      important as mechanisms of SR in biological systems are mostly unknown.

PMID- 21096530
TI  - Two dimensional spatial coherence of the natural vibrations of the biceps brachii
      muscle generated during voluntary contractions.
AB  - Surface mechanomyograms (S-MMGs) are recorded from low frequency (<100 Hz)
      mechanical oscillations that are naturally generated by skeletal muscle during
      voluntary contractions. This study investigates a method to determine the
      propagation directionality of the S-MMG waves. A 3*5 grid of skin mounted
      accelerometers was mounted on the biceps brachii muscle during submaximal
      voluntary contractions. This method resulted in findings that the propagation
      directionality of the S-MMGs are frequency dependent. At high frequencies (>25
      Hz), high spatial coherence values were only measured for sensor pairs aligned
      along the proximal to distal (i.e. longitudinal) orientation, thus indicating
      that coherent S-MMG were mainly propagating along the muscle fibers direction of
      the biceps brachii at those frequencies. On the other hand, at lower frequencies
      (<25 Hz), the S-MMG spatial coherence values did not exhibit a specific
      directionality. This method provides results that have an important implication
      of finding the average phase velocity of the propagating S-MMG wave, which can be
      used to determine viscoelastic properties of skeletal muscles.

PMID- 21096531
TI  - Validation of the Forced Oscillation Technique in the diagnostic of respiratory
      changes in patients with silicosis.
AB  - Silicosis is a typical occupational respiratory disease characterized by
      irreversible alterations throughout the alveolar and interstitial structure. The
      objectives of this study were (1) investigate the potential of the Forced
      Oscillation Technique (FOT) in the analysis of the patients with silicosis, and
      (2) evaluate the ability of FOT to identify early alterations in the respiratory
      mechanics of these patients. Sixty-one volunteers were analyzed: 20 healthy
      subjects and 41 with silicosis; these, were divided into 4 groups according to
      spirometric results: normal spirometric exam (n = 11); mild obstruction (n = 20);
      moderate and severe obstruction (n = 10.). A significant (p<0.0001) increase in
      total resistance (R0) and mean resistance (Rm) were observed, as well as a
      decrease in the dynamic compliance (p<0.0003) and mean reactance (p<0.000004). R0
      and Rm obtained adequate accuracy for clinical use (>80%). FOT parameters
      adequately described the pathophysiological changes associated with silicosis and
      presented adequate accuracy for clinical use, indicating that this technique can
      be helpful in the evaluation respiratory mechanics in this disease.

PMID- 21096532
TI  - Study to prevent the density of microcapsules from diffusing in blood vessel by
      local acoustic radiation force.
AB  - We have already reported our attempt to constrain direction of microcapsules in
      flow owing to an acoustic radiation force. However, the diameter of capsules was
      too large not to be applied in vivo. Furthermore, acoustic radiation force
      affected only in focal area because focused ultrasound was used. Thus we have
      improved our experiment by using microcapsules as small as blood cells and
      introducing a plane wave of ultrasound. We prepared an artificial blood vessel
      including a Y-form bifurcation established two observation areas. Then we newly
      defined the induction index to evaluate the difference of capsule density in two
      paths of downstream. As the result, optimum angle of ultrasound emission to
      induce to desired path was derived. And the induction index increased in
      proportion to the central frequency of ultrasound, which is affected by forming
      aggregation of capsules to receive more radiation force.

PMID- 21096533
TI  - Learning curves of the X Ray innovated process in the imaging Department of the
      National Institute of Respiratory Diseases, Mexico.
AB  - The impact within a known process due to the introduction of new technology may
      entail many factors such as workflow modification, increase of wait time,
      modification in service quality, and even cultural changes. The inclusion of
      these factors into a process affects its performance, but the implementation of
      innovations may counteract the impact and could even enhance the process. The
      objective of this work was to evaluate the impact of the innovations implemented
      in the X Ray process by the estimation of the learning curves and the estimated
      time in which the maximum learning may be reached.

PMID- 21096534
TI  - Risk analysis for intraoperative liver surgery.
AB  - Hepatic vessel structure is very important to ensure the blood supply of the
      liver tissue. Therefore the knowledge of the hepatic vessel system is
      indispensable in liver surgery planning, for example before performing a liver
      resection. The purpose of this paper is to present an easy to use and fast method
      concerning hepatic vessel segmentation and risk analysis, which is intended to be
      applicable in clinical routine.

PMID- 21096535
TI  - Decision process model to the health technology incorporation.
AB  - This study shows a decision model to the indicators acquisition in hospital
      medical equipment incorporation, based on three domains: decision making,
      technology assessment and Health Technology (HT) incorporation. When decision
      making is concerned, an analysis, synthesis and valuation context are approached,
      as well as the relation to the ways of making both being reflective or deliberate
      decision. The technology assessment domain corresponds to the choice and applying
      of multi-criteria methods in supporting the decision, such as: Analytic Hierarchy
      Process (AHP), Multi-Attribute Failure Mode Analysis (MAFMA), Elimination and
      Choice Translating Reality (ELECTRE) among others. On the other hand, the HT
      incorporation domain, the stages of incorporation of HT, which are divided in
      planning, proposal production and receiving, installation and management. From
      all of this, a supporting model to the decision to create indicators within the
      HT incorporation process, as well as to the HT management was obtained. The
      modeling of the incorporation process, through architecture of three domains,
      aids the Clinical Engineering need in managing of the medical hospital technology
      intending to an adequate usage. With the proposed methodology, one can obtain
      indicators to assist decision making in the process of HT incorporation.

PMID- 21096536
TI  - Clinical engineering and risk management in healthcare technological process
      using architecture framework.
AB  - This paper presents a model that aids the Clinical Engineering to deal with Risk
      Management in the Healthcare Technological Process. The healthcare technological
      setting is complex and supported by three basics entities: infrastructure (IS),
      healthcare technology (HT), and human resource (HR). Was used an Enterprise
      Architecture - MODAF (Ministry of Defence Architecture Framework) - to model this
      process for risk management. Thus, was created a new model to contribute to the
      risk management in the HT process, through the Clinical Engineering viewpoint.
      This architecture model can support and improve the decision making process of
      the Clinical Engineering to the Risk Management in the Healthcare Technological
      process.

PMID- 21096537
TI  - Modeling of ubiquitous technology integration process in health services.
AB  - Healthcare Development Framework (HDF) is a methodology of HL7 standard for
      development interoperability specifications in the healthcare. HDF was used in
      the process, artifacts and development of the information exchange messages. This
      paper presents a model of integration and interoperability process with
      information and communication technology (ICT) in emergency services, using the
      standard HL7 and RFID devices, as part of a platform for ubiquitous healthcare.

PMID- 21096538
TI  - Stiffness and position control of a prosthetic wrist by means of an EMG
      interface.
AB  - In this paper, we present a novel approach for decoding electromyographic signals
      from an amputee and for interfacing them with a prosthetic wrist. The model for
      the interface makes use of electromyographic signals from electrodes placed in
      agonistic and antagonistic sides of the forearm. The model decodes these signals
      in order to control both the position and the stiffness of the wrist.

PMID- 21096539
TI  - Bio-inspired mechanical design of a tendon-driven dexterous prosthetic hand.
AB  - This paper presents the preliminary design of a new dexterous upper-limb
      prosthesis provided with a novel anthropomorphic hand, a compact wrist based on
      bevel gears and a modular forearm able to cover different levels of upper-limb
      amputations. The hand has 20 DoFs and 11 motors, with a dexterous three fingered
      subsystem composed by a fully actuated thumb, and an hybrid index and middle
      fingers to enable dexterous manipulation and enhance grasp performance.

PMID- 21096540
TI  - Mechanomyographic response during FES in healthy and paraplegic subjects.
AB  - Mechanomyography (MMG) registers lateral oscillations of contracting muscles.
      Functional electrical stimulation (FES) improves the rehabilitation of paraplegic
      subjects and can be used in neuroprosthesis control. During FES application,
      muscular contraction responses may vary, possibly due to fatigue or adaptation of
      nerve cells face to electrical stimuli. This study measured the differences in
      MMG RMS and median frequency (MF) features between healthy (HV) and spinal cord
      injury (SCI) volunteers. Ten HV and three SCI participated in the research. FES
      waveform consisted of a monophasic square wave, 1kHz pulse frequency, 100us
      active pulse period and 3ms active burst period with burst frequency of 70Hz. For
      each stimulation series, three analysis windows were inspected. RMS and MF
      variations were inversely related. The obtained results may help to create new
      strategies of muscular closed-loop control.

PMID- 21096541
TI  - Real time breathing rate estimation from a non contact biosensor.
AB  - An automated real time method for detecting human breathing rate from a non
      contact biosensor is considered in this paper. The method has low computational
      and RAM requirements making it well-suited to real-time, low power implementation
      on a microcontroller. Time and frequency domain methods are used to separate a
      15s block of data into movement, breathing or absent states; a breathing rate
      estimate is then calculated. On a 1s basis, 96% of breaths were scored within 1
      breath per minute of expert scored respiratory inductance plethysmography, while
      99% of breaths were scored within 2 breaths per minute. When averaged over 30s,
      as is used in this respiration monitoring system, over 99% of breaths are within
      1 breath per minute of the expert score.

PMID- 21096542
TI  - The effect of lossy ECG compression on QRS and HRV feature extraction.
AB  - This paper describes the performance of beat detection and heart rate variability
      (HRV) feature extraction on electrocardiogram signals which have been compressed
      and reconstructed with a lossy compression algorithm. The set partitioning in
      hierarchical trees (SPIHT) compression algorithm was used with sixteen
      compression ratios (CR) between 2 and 50 over the records of the MIT/BIH
      arrhythmia database. Sensitivities and specificities between 99% and 85% were
      computed for each CR utilised. The extracted HRV features were between 99% and
      82% similar to the features extracted from the annotated records. A notable
      accuracy drop over all features extracted was noted beyond a CR of 30, with falls
      of 10% accuracy beyond this compression ratio.

PMID- 21096543
TI  - R-point detection for noise affected ECG recording through signal segmentation.
AB  - In this work we propose a novel approach for filtering noise-affected
      electrocardiogram (ECG) signals. The proposed method, mainly based on signal
      approximation by means of linear segments, has been applied for R-peaks
      recognition and has been compared with both cardiologists' manual marking and the
      automatic Laguna's method. The obtained results show that when compared to the
      Laguna's method the proposed algorithm provides a smaller mean error and a better
      error distribution.

PMID- 21096544
TI  - Improving phase congruency for EEG data reduction.
AB  - Real signals are often corrupted by noise. In applications where the noise power
      spectrum is variable with time, dynamic noise estimation and compensation can
      potentially improve the performance of signal processing algorithms. One such
      application is scalp EEG monitoring in epilepsy, where the electrical activity
      generated by cranio-facial muscle contraction and expansion, often obscures the
      measured brainwave signals. This work presents a data reduction algorithm which
      is based on differentiating interictal from normal background activity, in
      epileptic scalp EEG signals, using a modified phase congruency technique. The
      modification is based on dynamically estimating muscle activity from the signal
      and incorporating this estimation in phase congruency computations. The proposed
      algorithm identifies 90%of interictal spikes whilst transmitting only 45% of EEG
      data. This is in the order of 15% improvement in data reduction when compared to
      the performance obtained with the state-of-the-art denoised phase congruency
      which calculates a constant noise threshold-applied to the same dataset.

PMID- 21096545
TI  - Standard filter approximations for low power Continuous Wavelet Transforms.
AB  - Analogue domain implementations of the Continuous Wavelet Transform (CWT) have
      proved popular in recent years as they can be implemented at very low power
      consumption levels. This is essential for use in wearable, long term
      physiological monitoring systems. Present analogue CWT implementations rely on
      taking mathematical a approximation of the wanted mother wavelet function to give
      a filter transfer function that is suitable for circuit implementation. This
      paper investigates the use of standard filter approximations (Butterworth,
      Chebyshev, Bessel) as an alternative wavelet approximation technique. This
      extends the number of approximation techniques available for generating analogue
      CWT filters. An example ECG analysis shows that signal information can be
      successfully extracted using these CWT approximations.

PMID- 21096546
TI  - A 8.9-ENOB 2.5-epsilonW 150-KS/s non-binary redundant successive approximation
      ADC in 0.18-microm CMOS for bio-implanted devices.
AB  - A successive approximation analog-to-digital converter (SAR ADC) with a split
      capacitor switching scheme implementing the generalized non-binary redundant SAR
      algorithm and an energy efficient level shifter is proposed for bio-implanted
      applications. The generalized non-binary redundant SAR algorithm removes the
      radix constraint in conventional non-binary redundant SAR algorithm, and the
      energy efficient level shifter allows optimal power supplies to be chosen
      independently for the analog and digital blocks. A FOM of 34.7fJ/step has been
      achieved.

PMID- 21096547
TI  - A novel RF-based propagation model with tissue absorption for location of the GI
      tract.
AB  - In order to accurately estimate (build) the radio signal propagation attenuation
      model, especially inside the gastro-intestine (GI) tract of the human body, the
      Radio Frequency (RF) absorption characterization in human body is investigated.
      This characterization provides a criterion to design the Received Signal Strength
      (RSS) based localization system for the objective inside the human body. In this
      paper, the Specific Absorption Rate (SAR), E-field, H-field of the near and far
      field are investigated at frequencies of 434MHz, 868MHz, 1.2GHz and 2.4GHz
      respectively. Then, the numerical electromagnetic analysis with the finite
      differencetime-domain (FDTD) is applied to model the in vivo radio propagation
      channels by using a dipole antenna. Finally, simulation experiments are carried
      out in homogenous and heterogeneous mediums. The results show that the
      electromagnetic (EM) propagation is not only distance and orientation dependent,
      but also tissue absorption dependent in human body. The proposed model is in
      agreement with measurements in the simulation experiments.

PMID- 21096548
TI  - Touch-less heartbeat detection and measurement-based cardiopulmonary modeling.
AB  - This paper presents a system for touch-less heartbeat detection and a
      cardiopulmonary signal modeling approach. Using a vector network analyzer, a
      microwave system is tested for the detection of the heartbeat signal at a
      distance of 1 m from a person. The proposed system shows the ability of detecting
      the heartbeat signals with the possibility of tuning both frequency and power.
      Measurements are performed at 2.4, 5.8, 10, 16, and 60 GHz, as well as at
      different power levels between 0 and -27 dBm. Based on measurements performed for
      both respiration and heart beatings, a model of the measured signals representing
      the cardiopulmonary activity is presented. The heartbeat rate and the heart rate
      variability are extracted from the modeling signal using wavelet and classic
      filters, for SNR between 0 and -20 dB.

PMID- 21096549
TI  - Bandwidth tunable amplifier for recording biopotential signals.
AB  - This paper presents a low noise, low power, bandwidth tunable amplifier for bio
      potential signal recording applications. By employing depletion-mode pMOS
      transistor in diode configuration as a tunable sub pA current source to adjust
      the resistivity of MOS-Bipolar pseudo-resistor, the bandwidth is adjusted without
      any need for a separate band-pass filter stage. For high CMRR, PSRR and dynamic
      range, a fully differential structure is used in the design of the amplifier. The
      amplifier achieves a midband gain of 39.8dB with a tunable high-pass cutoff
      frequency ranging from 0.1Hz to 300Hz. The amplifier is fabricated in
      0.18epsilonm CMOS process and occupies 0.14mm(2) of chip area. A three electrode
      ECG measurement is performed using the proposed amplifier to show its feasibility
      for low power, compact wearable ECG monitoring application.

PMID- 21096550
TI  - Bio-recognition capability of Streptomyces sp. M7 evaluated in adverse conditions
      for use as a biological transducer in a Lindane biosensor.
AB  - Bio-recognition devices have captured special attention because they combine
      biological specificity and selectivity with electronics to perform environmental
      and biomedical analysis. Lindane is a recalcitrant pesticide considered potential
      carcinogen that has caused serious pollution problems. The purpose of the present
      study is to evaluate Streptomyces sp. M7 ability to dechlorinate lindane in
      liquid defined media in adverse culture conditions. Bacterial activity was
      monitored by electrochemical impedance spectroscopy. These results confirm that
      the microorganism adhered to a solid support is able to grow and to metabolize
      the organochlorine pesticide as a sole carbon source. Therefore, Streptomyces sp.
      M7 can be applied for a future development of a prototype for lindane detection
      and quantification.

PMID- 21096551
TI  - Novel sensing materials for breath analysis devices.
AB  - The development of new transition metal complexes (TMCs) sensing materials, based
      on di-rhodium (II,II) complexes with a lantern structure, is investigated.
      Specifically, in this work is reported a study carried out with the Rh2(form)4
      complex having the formamidinate (form = N.N-p-tolylformamidinate anion) bridging
      ligand in the equatorial positions. Thick films of the complex have been
      deposited on interdigitated alumina substrate and their electrical
      characteristics have been evaluated. Rh2(form)4 behaves as a p-type
      semiconductor, showing a large decrease in forward and reverse current in
      presence of ammonia vapors in air. The preliminary results reported promise a
      practical application of the developed devices in the breath analysis for
      clinical diagnostics.

PMID- 21096552
TI  - Finding discriminative subtypes of aggressive brain tumours using magnetic
      resonance spectroscopy.
AB  - Aggressive tumour types such as glioblastomas (gl) and metastases (me) are known
      to be difficult to discriminate on the basis of single-voxel proton magnetic
      resonance spectroscopy (SV 1H-MRS) information. Each of them is also
      heterogeneous in nature and a statistically robust subtyping analysis is likely
      to shed light on their structure and, possibly, on their differences. In this
      brief paper we carry out such analysis. From the original MRS frequencies and
      their first derivative approximation, the most discriminant variables are first
      selected by chi(2)-testing. Subtypes are then discovered in the distribution of
      gl and me by repeated model based cluster analysis. Then, the mean of each
      subtype is contrasted with the original distribution of MRS spectra by t-testing
      with tail probabilities for the proportion of false positive (TPPFP) control.
      Finally, the distribution of gl and me in each subtype is compared with random
      expectation by chi(2)-testing. The experimental results confirm the existence of
      consistent subtypes. They exhibit relative proportions of gl and me very unlikely
      to occur at random.

PMID- 21096553
TI  - How many clusters to report: a recursive heuristic.
AB  - Clustering can be a valuable tool for analyzing large amounts of data, but anyone
      who clusters must choose how many item clusters, K, to report. Unfortunately, one
      must guess at K or some related parameter when working within each of the three
      available frameworks where one thinks of clustering: as a Euclidean distance
      problem; as a statistical model problem; or as a complexity theory problem. We
      report here a novel recursive square root heuristic, RSQRT, which accurately
      predicts K(reported) as a function of the attribute or item count, depending on
      attribute scales. We tested the heuristic on 226 widely-varying, but mostly
      scientific, studies, and found that the heuristic's K(best-predicted) rounded to
      exactly K(reported) in over half of the studies and was close in almost all of
      them. We claim that this strongly-supported heuristic makes sense and that,
      although it is not prescriptive, using it prospectively is much better than
      guessing.

PMID- 21096554
TI  - PSS-SQL: protein secondary structure - structured query language.
AB  - Secondary structure representation of proteins provides important information
      regarding protein general construction and shape. This representation is often
      used in protein similarity searching. Since existing commercial database
      management systems do not offer integrated exploration methods for biological
      data e.g. at the level of the SQL language, the structural similarity searching
      is usually performed by external tools. In the paper, we present our newly
      developed PSS-SQL language, which allows searching a database in order to
      identify proteins having secondary structure similar to the structure specified
      by the user in a PSS-SQL query. Therefore, we provide a simple and declarative
      language for protein structure similarity searching.

PMID- 21096555
TI  - Fast orthogonal search for genetic feature selection.
AB  - In this paper, we present the application of a multivariate regression approach,
      fast orthogonal search, to select the most informative features in Single
      Nucleotide Polymorphism data, and to use these features to accurately model the
      entire data. Our results on two published datasets show very high accuracies in
      capturing the hidden information in the sequence of studied SNPs. The execution
      time for our developed methodology is very short and paves the way for its
      application to large-scale genome wide datasets.

PMID- 21096557
TI  - Design of a pulse oximeter for price sensitive emerging markets.
AB  - While the global market for medical devices is located primarily in developed
      countries, price sensitive emerging markets comprise an attractive, underserved
      segment in which products need a unique set of value propositions to be
      competitive. A pulse oximeter was designed expressly for emerging markets, and a
      novel feature set was implemented to reduce the cost of ownership and improve the
      usability of the device. Innovations included the ability of the device to
      generate its own electricity, a built in sensor which cuts down on operating
      costs, and a graphical, symbolic user interface. These features yield an average
      reduction of over 75% in the device cost of ownership versus comparable pulse
      oximeters already on the market.

PMID- 21096556
TI  - A knowledge engineering approach to recognizing and extracting sequences of
      nucleic acids from scientific literature.
AB  - In this paper we present a knowledge engineering approach to automatically
      recognize and extract genetic sequences from scientific articles. To carry out
      this task, we use a preliminary recognizer based on a finite state machine to
      extract all candidate DNA/RNA sequences. The latter are then fed into a knowledge
      based system that automatically discards false positives and refines noisy and
      incorrectly merged sequences. We created the knowledge base by manually analyzing
      different manuscripts containing genetic sequences. Our approach was evaluated
      using a test set of 211 full-text articles in PDF format containing 3134 genetic
      sequences. For such set, we achieved 87.76% precision and 97.70% recall
      respectively. This method can facilitate different research tasks. These include
      text mining, information extraction, and information retrieval research dealing
      with large collections of documents containing genetic sequences.

PMID- 21096558
TI  - Development of a microbicide-releasing diaphragm as an HIV prevention strategy.
AB  - Contraceptive diaphragms offer a discreet method of pregnancy protection that
      women can use when needed with no side effects. Incorporating antiretroviral HIV
      microbicides into such devices may also provide protection against HIV infection.
      The paper gives a brief outline of the work being conducted by PATH, CONRAD and
      QUB on the development of a microbicide-releasing SILCS diaphragm. The design,
      engineering and manufacturing challenges that have been encountered will be
      discussed, as well as the potential impact such a device could have in the
      developing world.

PMID- 21096559
TI  - Low-cost, portable optical imaging systems for cancer diagnosis.
AB  - Worldwide incidence and mortality rates due to cancer continue to rise, with the
      burden of disease increasingly shifting to developing countries. Several optical
      diagnostic methods such as diffuse optical tomography, wide-field
      autofluorescence imaging, confocal microscopy, and optical coherence tomography,
      are currently under development to enable earlier detection of cancer. However,
      these are primarily intended for use in healthcare facilities in industrialized
      countries. Using knowledge gained from early clinical studies with these large
      scale systems, we have designed and tested low-cost, portable versions of these
      instruments. We propose that these systems may be used for early diagnosis and
      screening in developing countries, and that pilot clinical studies are warranted
      in these low-resource settings.

PMID- 21096560
TI  - Non-instrumented nucleic acid amplification (NINA): instrument-free molecular
      malaria diagnostics for low-resource settings.
AB  - We have achieved the first complete, non-instrumented nucleic acid amplification
      test (NAAT) using a calcium oxide heat source thermally linked to an engineered
      phase change material. These two components alone maintain a thermal profile
      suitable for the loop-mediated isothermal amplification assay. Starting with
      computational fluid dynamics analysis, we identified nominal geometry for the
      exothermic reaction chamber, phase change material chamber, thermal insulation,
      and packaging. Using this model, we designed and fabricated an alpha prototype
      assay platform. We have verified the function of this multi-pathogen-capable
      platform with both fluorescent and visual turbidity indications using samples
      spiked with malaria DNA. Both the exothermically heated platform samples and
      samples heated on a Perkin-Elmer GeneAmp9600 thermocycler were first incubated at
      62 degrees C for 45 minutes, then heated to 95 degrees C to terminate enzyme
      activity, then analyzed. Results from the exothermically heated, non-instrumented
      platform were comparable to those from the thermocycler. These developments will
      enable point-of-care diagnostics using accurate NAATs which until now have
      required a well-equipped laboratory. The aim of this research is to provide
      pathogen detection with NAAT-level sensitivity in low-resource settings where
      assays such as immunochromatographic strip tests are successfully used but where
      there is no access to the infrastructure and logistics required to operate and
      maintain instrument-based diagnostics.

PMID- 21096561
TI  - Designing an early stage prototype using readily available material for a
      neonatal incubator for poor settings.
AB  - A clinical gap remains between the need for and the availability of functioning
      incubators to address the burden of neonatal mortality in poor settings.
      Increased referral capacity and demand for facility-based deliveries will
      necessitate enhanced care capacity. Rapid dysfunction of donated equipment is not
      only demoralizing to providers and patient families, but also presents a
      disincentive for timely referral to facilities. We expect a sustainable incubator
      that meets target clinical needs can serve as a training catalyst for providers
      to learn aspects along the continuum of newborn care. Many of these skills either
      do not require or may obviate the need for a newborn to be in such a device. Far
      from being a competitor to functioning approaches to thermo-regulation in
      resource-limited settings, a high- functioning and sustainable device targeted
      for district level hospitals can work collaboratively along the continuum of
      newborn care. Meeting this need will help ensure survival of imminently
      preventable causes of childhood mortality.

PMID- 21096562
TI  - Sound event detection in remote health care - small learning datasets and over
      constrained Gaussian Mixture Models.
AB  - The use of Gaussian Mixture Models (GMM), adapted through the Expectation
      Minimization (EM) algorithm, is not rare in Audio Analysis for Surveillance
      Applications and Environmental sound recognition. Their use is founded on the
      good qualities of GMM models when aimed at approximating Probability Density
      Functions (PDF) of random variables. But in some cases, where models are to be
      adapted from small sample sets instead of large but generic databases, a problem
      of balance between model complexity and sample size may play an important role.
      From this perspective, we show, through simple sound classification experiments,
      that constrained GMM, with fewer degrees of freedom, as compared to GMM with full
      covariance matrices, provide better classification performances. Moreover,
      pushing this argument even further, we also show that a Parzen model can do even
      better than usual GMM.

PMID- 21096563
TI  - Telemedicine enabled remote critical care ventilator.
AB  - Following a critical illness, technology-dependent children on chronic ventilator
      support require specialized care to facilitate recovery and rehabilitation that
      minimally impedes social and psychological development. Intervention strategies
      have been confounded by the need for frequent assessment via physical exam in a
      relatively immobile patient population. The availability of technology that
      enables effective, timely, and reliable information transfer between the homecare
      providers and the attending pulmonologist is likely to decrease the need for
      transport and hospitalization, and provide a dramatically increased level of
      comfort for care givers in the home and ultimately the children. A Pulmonetic
      Systems LTV 1200 ventilator was enabled with a wireless cellular interface to
      make its settings and performance data real-time accessible over a secure
      wireless Internet connection. A complete web-browser ventilator interface program
      was specified, coded, and tested. The live web interface was used to support a
      formal survey of pediatric pulmonologists to help gauge the potential medical
      utility of the new remote interface to the ventilator. The survey results were
      overwhelmingly supportive of the concept, and the pulmonologists listed many
      varied ways that the data could have utility in their patient populations.

PMID- 21096564
TI  - RESPLA: a decision support framework for emergency resource planning.
AB  - In this paper, we propose a web based framework, RESPLA that can assist resource
      managers in emergency resource planning during the preparedness phase of the
      emergency management cycle. This framework computes the deployment schedule and
      associated response times of the required resources to a specific disaster site,
      given the location and available resources at each depot. Using a web based
      interface to Google maps, RESPLA enables the users (e.g. emergency managers) to
      change the resource depots' location, add/delete resource depots, and change the
      number and type of available resources at each depot. This framework can help
      resource planners analyze how moving the resources from one location to another
      and adding new depots will affect the response times for a particular region.
      Moreover, analyzing the information about the response times will help
      communities in requesting additional resources.

PMID- 21096565
TI  - ANTEROCOD: actuarial survival curves applied to medical coding support for
      chronic diseases.
AB  - For the practitioner, choosing diagnosis codes is a non-intuitive operation.
      Mistakes are frequent, causing severe consequences on healthcare performance
      evaluation and funding. French physicians have to assign a code to all their
      activities and are frequently prone to these errors. Given that most of the time
      and particularly for chronic diseases indexed information is already available,
      we propose a tool named AnterOcod, in order to support the medical coding task.
      It suggests the list of most relevant plausible codes, predicted from the
      patient's earlier hospital stays, according to a set of previously utilized
      diagnosis codes. Our method applies the estimation of code reappearance rates,
      based on an equivalent approach to actuarial survival curves. Around 33% of the
      expected correct diagnosis codes were retrieved in this manner, after evaluating
      998 discharge abstracts, significantly improving the coding task.

PMID- 21096566
TI  - Fast and accurate calibration of an X-ray imager to an electromagnetic tracking
      system for interventional cardiac procedures.
AB  - Cardiovascular disease affects millions of Americans each year. Interventional
      guidance systems are being developed as treatment options for some of the more
      delicate procedures, including targeted stem cell therapy. As advanced systems
      for such types of interventional guidance are being developed, electromagnetic
      (EM) tracking is coming in demand to perform navigation. To use this EM tracking
      technology, a calibration is necessary to register the tracker to the imaging
      system. In this paper we investigate the calibration of an X-ray imaging system
      to EM tracking. Two specially designed calibration phantoms have been designed
      for this purpose, each having a rigidly attached EM sensor. From a clinical
      usability point-of-view, we propose to divide this calibration problem into two
      steps: i) in initial calibration of the EM sensor to the phantom design using an
      EM tracked needle to trace out grooves in the phantom surface and ii)
      segmentation from X-ray images and 3D reconstruction of beads embedded in the
      phantom in a known geometric pattern. Combining these two steps yields and X-ray
      to-EM calibration accuracy of less than 1 mm when overlaying an EM tracked needle
      on X-ray images.

PMID- 21096568
TI  - Space-time independent component analysis: the definitive BSS technique to use in
      biomedical signal processing?
AB  - Independent Component Analysis (ICA) is a very common instantiation of the Blind
      Source Separation (BSS) problem. In the context of biomedical signal analysis,
      ICA is generally applied to multi-channel recordings of physiological phenomena
      in order to de-noise and extract meaningful information underlying the
      recordings. This paper assesses the Spatio-Temporal ICA (ST-ICA) framework, which
      uses both spatial and temporal information derived from multi-channel time-series
      to extract underlying sources. In contrast, the standard implementation of the
      ICA algorithm generally uses only limited spatial information to inform the
      separation process. One of the major steps in the implementation of any ICA
      algorithm is the selection of relevant components from the many ICA usually
      returns. With ST-ICA there is a rich data-set of components exhibiting spatial as
      well as temporal/spectral information that could be used to identify the
      underlying process subspaces extracted by the ST-ICA algorithm. This paper
      highlights the methodology for performing ST-ICA and assesses the possible ways
      in which process subspace identification may take place.

PMID- 21096567
TI  - Catheter steering using a Magnetic Resonance Imaging system.
AB  - A catheter is successfully bent and steered by applying magnetic gradients inside
      a Magnetic Resonance Imaging system (MRI). One to three soft ferromagnetic
      spheres are attached at the distal tip of the catheter with different spacing
      between the spheres. Depending on the interactions between the spheres,
      progressive or discontinuous/jumping displacement was observed for increasing
      magnetic load. This phenomenon is accurately predicted by a simple theoretical
      dipole interaction model.

PMID- 21096569
TI  - On joint diagonalization of cumulant matrices for independent component analysis
      of MRS and EEG signals.
AB  - An extension of the original implementation of JADE, named eJADE((1)) hereafter,
      was proposed in 2001 to perform independent component analysis for any
      combination of statistical orders greater than or equal to three. More precisely,
      eJADE((1)) relies on the joint diagonalization of a set of several cumulant
      matrices corresponding to different matrix slices of one or several higher order
      cumulant tensors. An efficient way, without lose of statistical information, of
      reducing the number of third and fourth order cumulant matrices to be jointly
      diagonalized is proposed in this paper. The resulting approach, named
      eJADE(3,4)((2)), can be interpreted as an improvement of the eJADE(3,4)((1))
      method. A performance comparison with classical methods is conducted in the
      context of MRS and EEG signals showing the good behavior of our technique.

PMID- 21096570
TI  - Weighted-PCA for unsupervised classification of cardiac arrhythmias.
AB  - A method that improves the feature selection stage for non-supervised analysis of
      Holter ECG signals is presented. The method corresponds to WPCA approach
      developed mainly in two stages. First, the weighting of the feature set through a
      weight vector based on M-inner product as distance measure and a quadratic
      optimization function. The second one is the linear projection of weighted data
      using principal components. In the clustering stage, some procedures are
      considered: estimation of the number of groups, initialization of centroids and
      grouping by means a soft clustering algorithm. In order to decrease the procedure
      computational cost, segment analysis, grouping contiguous segments and
      establishing union and exclusion criteria per each cluster, is carried out. This
      work is focused to classify cardiac arrhythmias into 5 groups, according to the
      standard of the AAMI (ANSI/AAMI EC57:1998/ 2003). To validate the method, some
      recordings from MIT/BIH arrhythmia database are used. By employing the labels of
      each recording, the performance is assessed with supervised measures (Se = 90.1%,
      Sp = 98.9% y Cp = 97.4%), enhancing other works in the literature that do not
      take into account all heartbeat types.

PMID- 21096571
TI  - Foetal PQRST extraction from ECG recordings using cyclostationarity-based source
      separation method.
AB  - This work proposes a novel foetal electrocardiogram (FECG) extraction approach
      based on the cyclostationary properties of the signal of interest. The problem of
      FECG extraction can easily fit in a blind source separation (BSS) framework;
      taking into account specific statistical nature of the signal, that one wants to
      extract, leads to an algorithm able to estimate the FECG contribution to ECG
      recordings where the maternal ECG is predominant. We show that the proposed
      procedure provides estimates of the FECGs PQRST complexes without incorporating
      any prior knowledge concerning PQRST features. Discussions about foetal heart
      rate variability (HRV) estimation and future works conclude this paper.

PMID- 21096572
TI  - Spatiotemporal ICA applied to retinotopic fMRI data.
AB  - We use two spatiotemporal Independent Component Analysis algorithms, stJADE and
      stSOBI, to analyse data from a retinotopic functional magnetic resonance imaging
      experiment and compare their performance to the analysis of the same data with
      the spatial ICA done with JADE. This kind of experimental setting has the
      advantage that the activation in the brain can be estimated fairly easily and
      therefore can be used as well defined benchmark. We show that stSOBI can
      outperform sJADE and exhibits quite stable behaviour while stJADE critically
      depends on the quality of the chosen parameter settings for each subject.

PMID- 21096573
TI  - Software simulation of unobtrusive falls detection at night-time using passive
      infrared and pressure mat sensors.
AB  - Falls and their related injuries are a major challenge facing elderly people. One
      serious issue related to falls among the elderly living at home is the 'long-lie'
      scenario, which is the inability to get up from the floor after a fall, followed
      by lying on the floor for 60 minutes, or more. Several studies of accelerometer
      and gyroscope-based wearable falls detection devices have been cited in the
      literature. However, when the subject moves around at night-time, such as making
      a trip from the bedroom to the toilet, it is unlikely that they will remember or
      even feel an inclination to wear such a device. This research will investigate
      the potential usefulness of an unobtrusive fall detection system, based on the
      use of passive infrared sensors (PIRs) and pressure mats (PMs), that will detect
      falls automatically by recognizing unusual activity sequences in the home
      environment; hence, decreasing the number of subjects suffering the 'long-lie'
      scenario after a fall. A Java-based wireless sensor network (WSN) simulation was
      developed. This simulation reads the room coordinates from a residential map, a
      path-finding algorithm (A*) simulates the subject's movement through the
      residential environment, and PIR and PM sensors respond in a binary manner to the
      subject's movement. The falls algorithm was tested for four scenarios; one
      scenario including activities of daily living (ADL) and three scenarios
      simulating falls. The simulator generates movements for ten elderly people (5
      female and 5 male; age: 50-70 years; body mass index: 25.85-26.77 kg/m(2)). A
      decision tree based heuristic classification model is used to analyze the data
      and differentiate falls events from normal activities. The sensitivity,
      specificity and accuracy of the algorithm are 100%, 66.67% and 90.91%,
      respectively, across all tested scenarios.

PMID- 21096574
TI  - Monitoring pulse and respiration with a non-invasive hydraulic bed sensor.
AB  - A hydraulic bed sensor has been developed to non-invasively monitor pulse and
      respiration during sleep. This sensor is designed for in-home use, to be part of
      an integrated sensor network for the early detection of illness and functional
      decline in elderly adults. Experience with another bed sensor has motivated a
      desire to acquire enhanced, quantitative data related to pulse and respiration.
      This paper describes a working prototype, the signal processing methods used to
      extract data from the constructed transducer, and results from preliminary
      testing.

PMID- 21096575
TI  - Personalized building-embedded and wearable monitoring infrastructures with
      mediated data transfer.
AB  - This paper presents the design, prototype implementation and results of two
      cooperating infrastructures for a vital sign-based multimodal monitoring. The
      building-embedded and wearable systems provide complementary measurements in
      human and share a data transfer channel where possible. Managed by the common
      server, both systems are configurable in order to follow the subject's state and
      specific needs. Indoor and outdoor tests for various subjects shows significant
      savings (up to 80%) of communication costs and extention (up to 42%) of the
      wearable system autonomy.

PMID- 21096576
TI  - Alert management for home healthcare based on home automation analysis.
AB  - Rising healthcare for elder and disabled people can be controlled by offering
      people autonomy at home by means of information technology. In this paper, we
      present an original and sensorless alert management solution which performs
      multimedia and home automation service discrimination and extracts highly regular
      home activities as sensors for alert management. The results of simulation data,
      based on real context, allow us to evaluate our approach before application to
      real data.

PMID- 21096577
TI  - ART - a new concept for an activity recorder and transceiver.
AB  - In this contribution, a new concept for an activity recorder and transceiver
      (ART) is presented. Among the many purposes ART can be used for, this
      contribution focuses on the development of personal assistant devices for an
      aging society. Instead of probing a patient's health only when illness occurs,
      ART offers the possibility to monitor a person ubiquitous in every day life in
      order e.g. to detect abnormal changes in behavior, mainly based on the recording
      of discrete events rather than continuous sensor data streams. ARTs are key
      elements to develop personal assistant devices that are able to support people
      especially with cognitive impairments to remain living independent and yet secure
      their home environments. In this document vital demands on such systems will be
      defined and systematically analyzed. Furthermore the system architecture and
      possible applications for ARTs will be presented.

PMID- 21096578
TI  - Minimal hardware Bluetooth tracking for long-term at-home elder supervision.
AB  - The ability to automatically detect the location of an elder within their own
      home is a significant enabler of remote elder supervision and interaction
      applications. This location information is typically generated via a myriad of
      sensors throughout the home environment. Even with high sensor redundancy, there
      are still situations where traditional elder monitoring systems are unable to
      resolve the location of the elder. This work develops a minimal infrastructure
      radio-frequency localisation system for long-term elder location tracking. An
      RFID room-labelling technique is employed and with it, the localisation system
      developed in this work is shown to exhibit superior performance to more
      traditional localisation systems in realistic long-term deployments.

PMID- 21096579
TI  - GIS and spatial analysis for costs and services optimization in neurological
      telemedicine.
AB  - Telemedicine is an integrated, biomedical and psychosocial, secondary prevention
      intervention, where a specialized team guides the patient and his family in the
      course of the disease by reducing the stress of caregivers and allowing patients
      to stay longer at home, reducing, consequently, costs related to go to the
      specialist clinic. Teleneurology is a part of Telemedicine which uses modern
      communication technologies to allow neurology to be practiced when the doctor and
      patient are not present in the same place, and possibly not at the same time.
      This study focuses on identifying regional spots as potential territorial
      stations for the telemedicine service through the GIS (Geographical Information
      System), a computerized systems that allows placement of data of different types
      and sources into one system to manage and form spatial relationships that allow
      the display and analysis of relationships of geographic, environmental, and
      population factors (Scholten & de Lepper, 1991). We analyzed the optimal location
      of territorial telemedicine spots in correspondence of general practitioner
      clinics. It could be intended as a way to involve general practitioners in the
      management of those patients. The aim of this study is to improve the quality of
      life of patients and their caregivers providing a continuity of care through this
      system that reduces the inconvenience of travel and related costs. We estimated,
      then, the reduction of costs for patients and care-givers joining the
      telemedicine service in terms of hours out of work.

PMID- 21096580
TI  - A system for ubiquitous fall monitoring at home via a wireless sensor network.
AB  - Accidental falls of our elderly, and physical injuries resulting, represent a
      major health and economic. Falls are the most common causes of serious injuries
      and a major health threats in the stratum of older population. Early detection of
      a fall is a key factor when trying to provide adequate care to the elderly person
      who has suffered an accident at home. In this paper, we present a support system
      for detecting falls of an elder person by a static wireless nonintrusive
      sensorial infrastructure based on heterogenous sensor nodes. This previous
      infrastructure, named AID (Alarm Intelligent Device), is an AAL (Ambient Assisted
      Living) system that allows to infer a potential fall. We have developed,
      different to other contributions, a specific low-power multi-hop network consists
      of nodes (Motes) that wirelessly communicate to each other and are capable of
      hopping radio messages to a base station where they are passed to a PC (or other
      possible client). The goal of this project is 1) to provide alerts to caregivers
      in the event of an accident, acute illness or strange (possibly dangerous)
      activities, and 2) to enable that authorized and authenticated caregivers by
      means of a itinerant wearable mote can be inserted into mesh and interact with
      it. In this paper, we describe an ubiquitous assistential monitoring system at
      home.

PMID- 21096581
TI  - Skill generalization relevant to robotic neuro-rehabilitation.
AB  - Upper limb extremity rehabilitation practices are increasingly involving robotic
      interaction for repetitive practice, and there is increasing skepticism whether
      such systems can provide the relevant practice that can be generalized (or
      transferred) to functional activities in the real world. Most importantly, will
      patients be able to generalize in three critical ways: (1) to unpracticed
      directions, (2) to unpracticed movement distances, and (3) to unpracticed weight
      eliminated conditions? Rather than presuming that patients could generalize in
      three conditions, this study tested whether there was any evidence of such
      generalization ability in healthy individuals. We found that there was some
      evidence in all conditions except for the ability of healthy subjects to
      generalize to large movements after practicing small. Such results suggest that
      larger robotic systems are advantageous for training the functional motions that
      can include large actions.

PMID- 21096582
TI  - Nonlinear, multiple-input modeling of cerebral autoregulation using Volterra
      Kernel estimation.
AB  - Autoregulation refers to the automatic adjustment of blood flow to supply the
      required oxygen and glucose and remove waste, in proportion to the tissue's
      requirement at any instant of time. For the brain, cerebral autoregulation is an
      active process by which cerebral blood flow is controlled at an approximately
      steady level despite changes in the arterial blood pressure. Robust assessment of
      the cerebral autoregulation by a model that characterizes this system has been
      the goal of many studies, searching for techniques that can be used in clinical
      scenarios to detect potentially dangerous impairment of control. Multiple input,
      single output (MISO) models can be used to assess autoregulation, and system
      parameters can be estimated from spontaneous beat-to-beat variations in arterial
      blood pressure (ABP) and breath-by-breath end-tidal carbon dioxide (P(ETCO2)) as
      inputs, and cerebral blood flow velocity (CBFV) as the output. In this study a
      non-linear, multivariate approach, based on Volterra-type kernel estimation
      models is employed. The results are compared with linear models as well as
      nonlinear single-input single-output (SISO) models. The normalized mean squared
      error was used as the criteria of performance of each model in assessing cerebral
      autoregulation. Our simulation results indicate that for relatively short signals
      (around 300 sec), nonlinear, multiple-input models based on Volterra systems
      performed best, though the benefit varied considerably between subjects. When
      using a fixed model for all recordings, a linear SISO model with ABP as input
      provided the smallest average modeling error.

PMID- 21096583
TI  - MEG analysis in Alzheimer's disease computing approximate entropy for different
      frequency bands.
AB  - The goal of this study was to analyze the magnetoencephalogram (MEG) background
      activity in patients with Alzheimer's disease (AD) using a regularity measure:
      approximate entropy (ApEn). This measure was computed for a broad band (0.5-40
      Hz) as well as typical frequency bands (delta, theta, alpha, beta and gamma).
      Five minutes of recording were acquired with a 148-channel whole-head
      magnetometer in 15 patients with probable AD and 15 elderly control subjects. Our
      results showed that AD patients' MEGs were more regular than controls' recordings
      at all frequency bands, with the exception of beta. Additionally, there were
      statistically significant differences (p < 0.01, Student's t-test) at the broad
      and delta bands. Using receiver operating characteristic curves, the highest
      accuracy (83.33%) was reached at delta band. These results suggest the usefulness
      of ApEn to gain a better understanding of dynamical processes underlying the MEG
      recording.

PMID- 21096584
TI  - Characterization of activity epochs in actimetric registries for infantile colic
      diagnosis: Identification and feature extraction based on wavelets and symbolic
      dynamics.
AB  - The diagnosis and therapy planning of high prevalence pathologies such as
      infantile colic can be substantially improved by statistical signal processing of
      activity/rest registries. Assuming that colic episodes are associated to activity
      episodes, diagnosis aid systems should be based on preprocessing techniques able
      to separate real activity from rest epochs, and feature extraction methods to
      identify meaningful indices with diagnostic capabilities. In this paper, we
      propose a two step diagnosis aid methodology for infantile colic in children
      below 3 months old. Identification of activity periods is performed by means of a
      wavelet based activity filter which does not depend on the acquisition device (as
      so far proposed methods do). In addition, symbolic dynamic analysis is used for
      extraction of discriminative indices from the activity time series. Results on
      real data yielded 100% sensitivity and 80% specificity in a study group composed
      of 46 cases and 10 control subjects.

PMID- 21096585
TI  - Comparison of median filter and discrete dyadic wavelet transform for noise
      cancellation in electrocardiogram.
AB  - Development of noise cancellation algorithm is essential to facilitate accurate
      detection of electrocardiogram (ECG) in mobile health and wearable medical
      devices. In this study, we captured ECG from 20 subjects when they were at rest
      and during routine activities. The motion artifact in ECG was filtered using two
      non-linear filters: median filter and discrete dyadic wavelet transform. Signal
      to-noise ratio (SNR) and computation time of the filters were determined. We
      found that median filter showed larger SNR (7.61+/-1.21 dB) than discrete dyadic
      wavelet transform did (5.35+/-1.34 dB). Conversely, discrete dyadic wavelet
      transform benefited to its short computation time. The algorithms of these non
      linear filters should be further investigated to achieve both high SNR and fast
      computation in wearable and mobile monitoring systems.

PMID- 21096586
TI  - Correntropy-based nonlinearity test applied to patients with chronic heart
      failure.
AB  - In this study we propose the correntropy function as a discriminative measure for
      detecting nonlinearities in the respiratory pattern of chronic heart failure
      (CHF) patients with periodic or nonperiodic breathing pattern (PB or nPB,
      respectively). The complexity seems to be reduced in CHF patients with higher
      risk level. Correntropy reflects information on both, statistical distribution
      and temporal structure of the underlying dataset. It is a suitable measure due to
      its capability to preserve nonlinear information. The null hypothesis considered
      is that the analyzed data is generated by a Gaussian linear stochastic process.
      Correntropy is used in a statistical test to reject the null hypothesis through
      surrogate data methods. Various parameters, derived from the correntropy and
      correntropy spectral density (CSD) to characterize the respiratory pattern,
      presented no significant differences when extracted from the iteratively refined
      amplitude adjusted Fourier transform (IAAFT) surrogate data. The ratio between
      the powers in the modulation and respiratory frequency bands R was significantly
      different in nPB patients, but not in PB patients, which reflects a higher
      presence of nonlinearities in nPB patients than in PB patients.

PMID- 21096587
TI  - MEFS - MIND electrical impedance tomography forward solver.
AB  - Electrical impedance tomography (EIT) offers a possibility of realizing of a low
      cost and safe modality for clinically monitoring patients being treated with
      mechanical ventilation. However, image reconstruction algorithm employed at
      different clinical or research settings varies from one to another, which in turn
      makes interpretation of regional ventilation across institutions difficult.
      Seeing the lack of a standardized algorithm, GREIT (Graz consensus Reconstruction
      algorithm for EIT) was proposed lately in an attempt to develop a unified EIT
      image reconstruction algorithm. To assess GREIT, an anatomically-detailed
      electrical model of the thorax is indispensable. In view of this need, we
      describe a high resolution, image-based electrical thoracic modeling software
      environment, named MEFS (MIND EIT Forward Solver). The software environment
      utilizes anatomically realistic geometry of the thorax, allows placing electrode
      of any shape interactively, and yields the detailed field information in the
      simulated volume. The goals of the development of MEFS are: 1) to generate
      electrical measurements needed for EIT image reconstruction, 2) to provide a
      platform to compare various EIT reconstruction algorithms.

PMID- 21096588
TI  - A comparison between compressed sensing algorithms in electrical impedance
      tomography.
AB  - Electrical Impedance Tomography (EIT) calculates the internal conductivity
      distribution within a body using electrical contact measurements. Conventional
      EIT reconstruction methods solve a linear model by minimizing the least squares
      error, i.e., the Euclidian or L2-norm, with regularization. Compressed sensing
      provides unique advantages in Magnetic Resonance Imaging (MRI) [1] when the
      images are transformed to a sparse basis. EIT images are generally sparser than
      MRI images due to their lower spatial resolution. This leads us to investigate
      ability of compressed sensing algorithms currently applied to MRI in EIT without
      transformation to a new basis. In particular, we examine four new iterative
      algorithms for L1 and L0 minimization with applications to compressed sensing and
      compare these with current EIT inverse L1-norm regularization methods. The four
      compressed sensing methods are as follows: (1) an interior point method for
      solving L1-regularized least squares problems (L1-LS); (2) total variation using
      a Lagrangian multiplier method (TVAL3); (3) a two-step iterative shrinkage /
      thresholding method (TWIST) for solving the L0-regularized least squares problem;
      (4) The Least Absolute Shrinkage and Selection Operator (LASSO) with tracing the
      Pareto curve, which estimates the least squares parameters subject to a L1-norm
      constraint. In our investigation, using 1600 elements, we found all four CS
      algorithms provided an improvement over the best conventional EIT reconstruction
      method, Total Variation, in three important areas: robustness to noise, increased
      computational speed of at least 40x and a visually apparent improvement in
      spatial resolution. Out of the four CS algorithms we found TWIST was the fastest
      with at least a 100x speed increase.

PMID- 21096589
TI  - Coronary artery segmentation using geometric moments based tracking and snake
      driven refinement.
AB  - Automatic or semi-automatic segmentation and tracking of artery trees from
      computed tomography angiography (CTA) is an important step to improve the
      diagnosis and treatment of artery diseases, but it still remains a significant
      challenging problem. In this paper, we present an artery extraction method to
      address the challenge. The proposed method consists of two steps: (1) a geometric
      moments based tracking to secure a rough centerline, and (2) a fully automatic
      generalized cylinder structure-based snake method to refine the centerlines and
      estimate the radii of the arteries. In this method, a new line direction based on
      first and second order geometric moments is adopted while both gradient and
      intensity information are used in the snake model to improve the accuracy. The
      approach has been evaluated on synthetic images as well as 8 clinical coronary
      CTA images with 32 coronary arteries. Our method achieves 94.7% overlap tracking
      ability within an average distance inside the vessel of 0.36 mm.

PMID- 21096590
TI  - Impact of tear location on hemodynamics in a type B aortic dissection
      investigated with computational fluid dynamics.
AB  - Stanford type B aortic dissections (TB-AD), which split the descending aorta in a
      true and false lumen, have better in-hospital survival than type A dissections
      affecting the ascending aorta. However, short-term and long-term prognosis for
      the individual patient remains challenging, with one in four patients not
      surviving after 3 years.

PMID- 21096591
TI  - Automatic tip selection for microtubule dynamics quantification.
AB  - Microtubule (MT) dynamics quantification includes modeling of elongation, rapid
      shortening, and pauses. It indicates the effect of the cancer treatment drug
      paclitaxel because the drug causes MTs to bundle, which will in turn inhibit
      successful mitosis of cancerous cells. Thus, automatic MT dynamics analysis has
      been researched intensely because it allows for faster evaluation of potential
      cancer treatments and better understanding of drug effects on a cell. However,
      most current literatures still use manual initialization. In this work, we
      propose an automatic initialization algorithm that selects isolated and active
      tips for tracking. We use a Gaussian match filter to enhance the MT structures,
      and a novel technique called Pixel Nucleus Analysis (PNA) for isolated MT tip
      detection. To find dynamic tips, we applied a masked FFT in the temporal domain
      followed by K-means clustering. To evaluate the selected tips, we used a low
      level tip linking algorithm, and show the results of applying the algorithm to a
      model image and five MCF-7 breast cancer cell line images captured using
      fluorescent confocal microscopy. Finally, we compare tip selection criteria with
      existing automatic selection algorithms. We conclude that the proposed analysis
      is an effective technique based on three criteria which include outer region
      selection, separation, and MT dynamics.

PMID- 21096593
TI  - Brain lesion detection in MRI with fuzzy and geostatistical models.
AB  - Automated image detection of white matter changes of the brain is essentially
      helpful in providing a quantitative measure for studying the association of white
      matter lesions with other types of biomedical data. Such study allows the
      possibility of several medical hypothesis validations which lead to therapeutic
      treatment and prevention. This paper presents a new clustering-based segmentation
      approach for detecting white matter changes in magnetic resonance imaging with
      particular reference to cognitive decline in the elderly. The proposed method is
      formulated using the principles of fuzzy c-means algorithm and geostatistics.

PMID- 21096592
TI  - A fully automatic algorithm for segmentation of the breasts in DCE-MR images.
AB  - Automatic segmentation of the breast and axillary region is an important
      preprocessing step for automatic lesion detection in breast MR and dynamic
      contrast-enhanced-MR studies. In this paper, we present a fully automatic
      procedure based on the detection of the upper border of the pectoral muscle.
      Compared with previous methods based on thresholding, this method is more robust
      to noise and field inhomogeneities. The method was quantitatively evaluated on 31
      cases acquired from two centers by comparing the results with a manual
      segmentation. Results indicate good overall agreement within the reference
      segmentation (overlap=0.79 +/- 0.09, recall=0.95 +/- 0.02, precision=0.82 +/-
      0.1).

PMID- 21096594
TI  - An improved cylindrical FDTD method and its application to field-tissue
      interaction study in MRI.
AB  - This paper presents a three dimensional finite-difference time-domain (FDTD)
      scheme in cylindrical coordinates with an improved algorithm for accommodating
      the numerical singularity associated with the polar axis. The regularization of
      this singularity problem is entirely based on Ampere's law. The proposed
      algorithm has been detailed and verified against a problem with a known solution
      obtained from a commercial electromagnetic simulation package. The numerical
      scheme is also illustrated by modeling high-frequency RF field-human body
      interactions in MRI. The results demonstrate the accuracy and capability of the
      proposed algorithm.

PMID- 21096595
TI  - Pectoral muscle detection in mammograms based on the shortest path with endpoints
      learnt by SVMs.
AB  - Automatic pectoral muscle removal on medio-lateral oblique view of mammogram is
      an essential step for many mammographic processing algorithms. However, the wide
      variability in the position of the muscle contour, together with the similarity
      between in muscle and breast tissues makes the detection a difficult task. In
      this paper, we propose a two step procedure to detect the muscle contour. In a
      first step, the endpoints of the contour are predicted with a pair of support
      vector regression models; one model is trained to predict the intersection point
      of the contour with the top row while the other is designed for the prediction of
      the endpoint of the contour on the left column. Next, the muscle contour is
      computed as the shortest path between the two endpoints. A comprehensive
      comparison with manually-drawn contours reveals the strength of the proposed
      method.

PMID- 21096596
TI  - Automatic colon polyp flagging via geometric and texture features.
AB  - Computer Tomographic Colonography, combined with computer-aided detection (CAD),
      is a promising emerging technique for colonic polyp analysis. We present a CAD
      scheme for polyp flagging based on new texture and geometric features that
      consider both the information in the candidate polyp location and its immediate
      surrounding area, testing multiple sizes. The proposed algorithm is tested with
      ground truth data, including flat and small polyps, with very promising results.

PMID- 21096597
TI  - Analysis of image quality parameter of conventional and dental radiographic
      digital images.
AB  - The image quality obtained by a radiographic equipment is very useful to
      characterize the physical properties of the image radiographic chain, in a
      quality control of the radiographic equipment. In the radiographic technique it
      is necessary that the evaluation of the image can guarantee the constancy of its
      quality to carry out a suitable diagnosis. In this work we have designed some
      radiographic phantoms for different radiographic digital devices, as dental,
      conventional, equipments with computed radiography (phosphor plate) and direct
      radiography (sensor) technology. Additionally, we have developed a software to
      analyse the image obtained by the radiographic equipment with digital processing
      techniques, as edge detector, morphological operators, statistical test for the
      detected combinations.. The design of these phantoms let the evaluation of a wide
      range of operating conditions of voltage, current and time of the digital
      equipments. Moreover, the image quality analysis by the automatic software, let
      study it with objective parameters.

PMID- 21096598
TI  - Anisotropic diffusion tensor applied to temporal mammograms: an application to
      breast cancer risk assessment.
AB  - Breast density is considered a structural property of a mammogram that can change
      in various ways explaining different effects of medicinal treatments. The aim of
      the present work is to provide a framework for obtaining more accurate and
      sensitive measurements of breast density changes related to specific effects like
      Hormonal Replacement Therapy (HRT) and aging. Given effect-grouped patient data,
      we demonstrated how the diffusion tensor and its coherence features computed in
      an anatomically oriented breast coordinate system followed by statistical
      learning scheme provides non subjective and reproducible measure, as compared to
      the traditional BIRADS and computer aided percent density measure. We also
      demonstrate how orientation of breast tissue changes in temporal study. This
      framework facilitates radiologist to assess breast tissue change and guide them
      to evaluate individual risk of having breast cancer.

PMID- 21096599
TI  - Application of fractal analysis to mammography.
AB  - We report on a morphological study of 192 breast masses as seen in mammograms,
      with the aim of discrimination between benign masses and malignant tumors. From
      the contour of each mass, we computed the fractal dimension (FD) and a few shape
      factors, including compactness, fractional concavity, and spiculation index. We
      calculated FD using four different methods: the ruler and box-counting methods
      applied to each 2-dimensional (2D) contour and its 1-dimensional signature. The
      ANOVA test indicated statistically significant differences in the values of the
      various shape features between benign masses and malignant tumors. Analysis using
      receiver operating characteristics indicated the area under the curve, A(z), of
      up to 0.92 with the individual shape features. The combination of compactness, FD
      with the 2D ruler method, and the spiculation index resulted in the highest A(z)
      value of 0.93.

PMID- 21096600
TI  - A model-based reconstruction method for 3-D rotational coronary angiography.
AB  - This paper presents a model-based reconstruction method of the coronary tree from
      a few number of projections in rotational angiography imaging. The reconstruction
      relies on projections acquired at a same cardiac phase and an energy function
      minimization that aims to lead the deformation of the 3D model to fit projection
      data whereas preserving coherence both in time and space. Some preliminary
      results are provided on simulated rotational angiograms.

PMID- 21096601
TI  - Fluence of thulium laser system in skin ablation.
AB  - Tm:YAP laser system at power levels up to 1.2 W at 1980 nm was established in
      both continuous-wave and modulated modes of operation. The fluence effect of the
      laser system for skin ablation was analyzed by histology analysis with Wistar rat
      skin tissues. Thermally altered length, thermally altered area, ablation area,
      and ablation depth parameters were measured on histology images of skin samples
      just after the laser operation and after four-day healing period. Continuous-wave
      mode of operation provided higher thermal effects on the skin samples. Lower
      fluence levels were found for efficient ablation effect.

PMID- 21096602
TI  - Temperature dependence of thermal conductivity of liver based on various
      experiments and a numerical simulation for RF ablation.
AB  - Radiofrequency ablation (RFA) for liver cancer has increasingly been used over
      the past few years because RFA is minimally invasive treatment for patients.
      However, precise control of the formation of coagulation zones is difficult for
      operators due to inadequate imaging modalities. With this in mind, we have
      proposed a model-based robotic ablation system using numerical simulation to
      analyze temperature distributions in the organ to overcome this deficiency. The
      objective of our work is to develop a temperature-dependent thermophysical organ
      model to construct a precise numerical simulator for RFA. However, no standard
      methods exist for obtaining the thermophysical properties of biological tissues,
      as detailed evaluations of the accuracy of properties obtained from various
      experiments have not been completed. The purpose of this study was thus to
      measure and model the temperature dependence of thermal conductivity in hog liver
      from three representative methods, and to compare these results using our
      developed numerical simulator to reveal differences in temperature distributions
      stemming from differences in thermal conductivities.

PMID- 21096603
TI  - Design and construction of a hyperthermia system with improved interaction of
      magnetic induction-heating.
AB  - For the applications of localized hyperthermia, an improved magnetic induction
      heating system is described. The associated components of this system, for
      example, coils for generating magnetic field, magnetic circuit for flux path, and
      ferrite needles for generating heat by magnetic induction, all have been
      explained. An animal experiment of induction-heating hyperthermia for rat's liver
      is also carried out, and the consequent pathology of Hematoxylin and Eosin (H&E)
      stain and NADPH oxidase activity assay are also conducted for evaluation.

PMID- 21096604
TI  - Heating properties of coaxial needle applicator made of SMA for hyperthermia
      treatments.
AB  - This paper describes heating properties of the developed coaxial needle
      applicator made of a shape memory alloy (SMA) for brain tumor hyperthermia
      treatments to avoid undesirable hotspots. We estimated the temperature
      distribution inside an agar phantom by the finite element method (FEM) and heated
      the agar phantom with the developed needle applicator.

PMID- 21096605
TI  - Effects of late sodium current enhancement during LQT-related arrhythmias. A
      simulation study.
AB  - Long QT syndrome is a repolarization disorder characterized by marked
      prolongation of QT interval. A clear consequence of long QT syndrome is the
      occurrence of a polymorphic ventricular tachycardia called Torsade de Pointes,
      which has been related to early after depolarizations (EADs) formation. This
      repolarizing disorder has been observed under pathological situations, such as
      heart failure, oxidative stress, ventricular hypertrophy and/or in the presence
      of pure class III antiarrhythmics. Under such pathologies electrophysiological
      changes affect the electrical activity of the cell. Lately, the enhancement of
      late sodium current (I(NaL)) and its role has become a source of interest. In
      this work, a mathematical model of I(NaL) has been proposed and incorporated to
      the ten Tussher model of the human ventricular action potential (AP),
      specifically in M cells. We simulated and analyzed the effects of I(NaL)
      enhancement in combination with LQT-related pathologies and administration of
      I(Kr) blockers, on the AP. This study demonstrates that I(NaL) prolongs AP
      duration (APD) in a rate-dependent manner. Indeed, a 10-fold increase of I(NaL)
      prolongs APD in 80% for a stimulation rate of 1 Hz and 100% for 0.25 Hz. Also,
      intracellular sodium concentration [Na(+)](i) significantly increases in the
      presence of enhanced I(NaL), increasing the probability of EADs formation through
      calcium overload in cells prone to develop EADs.

PMID- 21096606
TI  - Comparison of complex fractionated atrial electrograms at cellular scale using
      numerical and experimental models.
AB  - This study investigates the existence of the pseudo complex fractionated atrial
      electrogram (CFAE) at cellular level. Our assumptions are based on the fact that
      CFAEs are linked to the generation of the spiral waves. These are created using a
      numerical model and an experimental model of in vitro culture of neonatal rats
      cardiac cells. Pseudo bipolar electrograms resulting from these two models are
      compared qualitatively and some patterns could be identified as CFAE signature.

PMID- 21096607
TI  - Human and rabbit inter-species comparison of ionic mechanisms of arrhythmic risk:
      A simulation study.
AB  - Experimental studies of pro-arrhythmic mechanisms are scarcely performed in
      humans due to the limited availability of human cardiomyocytes. Subsequently,
      extrapolation of animal experimental research to humans is widely extended. Our
      aim is to systematically compare the ionic mechanisms of the main cellular
      biomarkers of arrhythmic risk between human and rabbit using computer
      simulations. For this purpose four stimulation protocols were applied to the
      Mahajan et al. rabbit ventricular action potential (AP) model for control
      conditions and for +/- 15 and +/- 30% variations in the ionic current
      conductances of the main repolarization currents to quantify cellular biomarkers.
      Sensitivity of every simulated biomarker to every parameter modification was
      compared to that obtained for human in our previous work. Our results show that
      the ionic mechanisms involved in AP triangulation, systolic intracellular calcium
      concentration and AP duration (APD) accommodation to abrupt changes of pacing
      rate are very similar in both species. Unfortunately, significant differences
      were found in the ionic mechanisms related to APD, restitution properties and
      rate dependence of intracellular calcium and sodium concentrations. In
      conclusion, extrapolation of experimental research in rabbit to humans is limited
      by the existence of species dependent ionic mechanisms. In addition, this
      analysis is very useful for understanding and improvement of mathematical models.

PMID- 21096608
TI  - Stochastic modelling of cardiac cell structure.
AB  - Anatomically realistic and biophysically based computational models of the heart
      have provided valuable insights into cardiac function in health and disease.
      Nevertheless, these models typically use a "black-box" approach to describe the
      cellular level processes that underlie the heart beat. We are developing
      techniques to stochastically generate three-dimensional models of mammalian
      ventricular myocytes that exhibit salient characteristics of the spatial
      organisation of key cellular organelles in cardiac cell excitation and
      contraction. Such anatomically detailed models will facilitate a deeper
      understanding of cardiac function at multiple scales. This paper presents an
      important first step towards understanding and modelling the spatial distribution
      of two key organelles in cardiac cell contraction - myofibrils and mitochondria.
      The sarcolemma, myofibrils and mitochondria were segmented from transmission
      electron micrographs of ventricular cells from a healthy wistar rat. The
      centroids of the myofibrils and mitochondria were calculated, and various spatial
      statistical techniques for characterising the centroid distribution and inter
      point interactions were investigated and implemented using the R spatstat
      package. Techniques for modelling the observed spatial patterns were also
      investigated, and preliminary results indicate that the Strauss Hard-core model
      best captures the interaction observed. We intend to confirm these results with
      larger sample of cells.

PMID- 21096609
TI  - From in vitro to in silico and back again: using biological and mathematical
      synergy to decipher breast cancer cell motility.
AB  - The complexity of biological systems is often prohibitive in testing specific
      hypotheses from first physical principles. To circumvent these limitations we
      used biological data to inform a mathematical model of breast cancer cell
      motility. Using this in silico model we were able to accurately assess the
      influence of actin cytoskeletal architecture on the motility of a genetically
      modified breast cancer cell line. Furthermore, using the in silico model revealed
      a biological phenomenon that has not been previously described in live cell
      movement. Fusing biology and mathematics as presented here represents a new
      direction for biomedical research in which advances in each field synergistically
      drive discoveries in the other.

PMID- 21096610
TI  - Moving dipoles method detects displacement in N2 and P3 generation in diffuse
      axonal injury patients.
AB  - Physiological neural mechanisms underlying attentional processes were
      investigated by means of moving dipoles method in survivors of diffuse axonal
      injury (DAI) and in a control group. N2 and P3 components were obtained by means
      of the administration of the Conner's Continuous Performance Test. Analysis of
      behavioral responses showed significant between-group differences in reaction
      times and error rates. A different number of dipoles was needed for the
      reconstruction of both N2 and P3 components in the two groups. The study of
      dipoles location revealed major displacements in damaged brains with respect to
      physiology. In conclusion, data from DAI patients showed that neuronal
      reorganization following brain injury evolves towards the generation of multiple
      central sources.

PMID- 21096611
TI  - Seizure onset detection based on a Uni- or multi-modal intelligent seizure
      acquisition (UISA/MISA) system.
AB  - An automatic Uni- or Multi-modal Intelligent Seizure Acquisition (UISA/MISA)
      system is highly applicable for onset detection of epileptic seizures based on
      motion data. The modalities used are surface electromyography (sEMG),
      acceleration (ACC) and angular velocity (ANG). The new proposed automatic
      algorithm on motion data is extracting features as "log-sum" measures of discrete
      wavelet components. Classification into the two groups "seizure" versus "non
      seizure" is made based on the support vector machine (SVM) algorithm. The
      algorithm performs with a sensitivity of 91-100%, a median latency of 1 second
      and a specificity of 100% on multi-modal data from five healthy subjects
      simulating seizures. The uni-modal algorithm based on sEMG data from the subjects
      and patients performs satisfactorily in some cases. As expected, our results
      clearly show superiority of the multi-modal approach, as compared with the uni
      modal one.

PMID- 21096612
TI  - Automatic sleep staging based on ballistocardiographic signals recorded through
      bed sensors.
AB  - This study presents different methods for automatic sleep classification based on
      heart rate variability (HRV), respiration and movement signals recorded through
      bed sensors. Two methods for feature extraction have been implemented: time
      variant-autoregressive model (TVAM) and wavelet discrete transform (WDT); the
      obtained features are fed into two classifiers: Quadratic (QD) and Linear (LD)
      discriminant for staging sleep in REM, nonREM and WAKE periods. The performances
      of all the possible combinations of feature extractors and classifiers are
      compared in terms of accuracy and kappa index, using clinical polysomographyc
      evaluation as golden standard. 17 recordings from healthy subjects, including
      also polisomnography, were used to train and test the algorithms. When automatic
      classification is compared. QD-TVAM algorithm achieved a total accuracy of 76.81
      +/- 7.51 % and kappa index of 0.55 +/- 0.10, while LD-WDT achieved a total
      accuracy of 79 +/- 10% and kappa index of 0.51 +/- 0.17. The results suggest that
      a good sleep evaluation can be achieved through non-conventional recording
      systems that could be used outside sleep centers.

PMID- 21096613
TI  - Automatic epileptic seizure onset detection using matching pursuit: a case study.
AB  - An automatic alarm system for detecting epileptic seizure onsets could be of
      great assistance to patients and medical staff. A novel approach is proposed
      using the Matching Pursuit algorithm as a feature extractor combined with the
      Support Vector Machine (SVM) as a classifier for this purpose. The combination of
      Matching Pursuit and SVM for automatic seizure detection has never been tested
      before, making this a pilot study. Data from red different patients with 6 to 49
      seizures are used to test our model. Three patients are recorded with scalp
      electroencephalography (sEEG) and three with intracranial electroencephalography
      (iEEG). A sensitivity of 78-100% and a detection latency of 5-18s has been
      achieved, while holding the false detection at 0.16-5.31/h. Our results show the
      potential of Matching Pursuit as a feature extractor for detection of epileptic
      seizures.

PMID- 21096614
TI  - Speech recognition features for EEG signal description in detection of neonatal
      seizures.
AB  - In this work, features which are usually employed in automatic speech recognition
      (ASR) are used for the detection of neonatal seizures in newborn EEG. Three
      conventional ASR feature sets are compared to the feature set which has been
      previously developed for this task. The results indicate that the thoroughly
      studied spectral envelope based ASR features perform reasonably well on their
      own. Additionally, the SVM Recursive Feature Elimination routine is applied to
      all extracted features pooled together. It is shown that ASR features
      consistently appear among the top-rank features.

PMID- 21096615
TI  - Feature subset selection for age-related changes in EEG and EMG during motor
      tasks.
AB  - The paper presents an ongoing investigation into the feasibility of
      distinguishing between healthy young and older adults, but more specifically into
      the nature of the features that would provide this distinction. The present study
      compared the performance of forward, backward, and branch and bound feature
      selection algorithms when applied to electroencephalography and electromyography
      data. The results showed that the forward selection algorithm outperformed the
      other techniques for this particular problem. In addition, time domain features
      were primarily selected over frequency domain features. Validation of the
      selected subset suggests the approach is appropriate for future investigation.

PMID- 21096616
TI  - Genetic feature selection to optimally detect P300 in brain computer interfaces.
AB  - A Brain Computer Interface is a system that provides an artificial communication
      between the human brain and the external world. The paradigm based on event
      related evoked potentials is used in this work. Our main goal was to efficiently
      solve a binary classification problem: presence or absence of P300 in the
      registers. Genetic Algorithms and Support Vector Machines were used in a wrapper
      configuration for feature selection and classification. The original input
      patterns were provided by two channels (Oz and Fz) of resampled EEG registers and
      wavelet coefficients. To evaluate the performance of the system, accuracy,
      sensibility and specificity were calculated. The wrapped wavelet patterns show a
      better performance than the temporal ones. The results were similar for patterns
      from channel Oz and Fz, together or separated.

PMID- 21096617
TI  - An information transmission measure for the analysis of effective connectivity
      among cortical neurons.
AB  - We present a methodology for detecting effective connections between
      simultaneously recorded neurons using an information transmission measure to
      identify the presence and direction of information flow from one neuron to
      another. Using simulated and experimentally-measured data, we evaluate the
      performance of our proposed method and compare it to the traditional transfer
      entropy approach. In simulations, our measure of information transmission
      outperforms transfer entropy in identifying the effective connectivity structure
      of a neuron ensemble. For experimentally recorded data, where ground truth is
      unavailable, the proposed method also yields a more plausible effective
      connectivity structure than transfer entropy.

PMID- 21096618
TI  - Fuzzy rule-based seizure prediction based on correlation dimension changes in
      intracranial EEG.
AB  - In this paper, we present a method for epileptic seizure prediction from
      intracranial EEG recordings. We applied correlation dimension, a nonlinear
      dynamics based univariate characteristic measure for extracting features from EEG
      segments. Finally, we designed a fuzzy rule-based system for seizure prediction.
      The system is primarily designed based on expert's knowledge and reasoning. A
      spatial-temporal filtering method was used in accordance with the fuzzy rule
      based inference system for issuing forecasting alarms. The system was evaluated
      on EEG data from 10 patients having 15 seizures.

PMID- 21096619
TI  - Cross-sampled GRAPPA for parallel MRI.
AB  - As one widely-used parallel-imaging method, Generalized Auto-calibrating
      Partially Parallel Acquisitions (GRAPPA) technique reconstructs the missing k
      space data by a linear combination of the acquired data using a set of weights.
      These weights are usually derived from auto-calibration signal (ACS) lines that
      are acquired in parallel to the reduced lines. In this paper, a cross sampling
      method is proposed to acquire the ACS lines orthogonal to the reduced lines. This
      cross sampling method increases the amount of calibration data along the
      direction that the k-space is undersampled and thus improves the calibration
      accuracy, especially when a small number of ACS lines are acquired. Both phantom
      and in vivo experiments demonstrate that the proposed method, named cross-sampled
      GRAPPA (CS-GRAPPA), can effectively reduce the aliasing artifacts of GRAPPA when
      high acceleration is desired.

PMID- 21096620
TI  - Cognitively driven brain machine control using neural signals in the parietal
      reach region.
AB  - This study demonstrates that the spiking and local field potential (LFP) activity
      in the parietal reach region (PRR) of the macaque monkey can be jointly used to
      control the location of the computer cursor when the correct target location must
      be inferred symbolically, e.g., leftward arrow for the leftward target, etc. The
      average correct target acquisition rate during this brain machine control task
      without actual movements was 86% for the six discrete target locations when using
      spikes and LFPs from 16 electrodes. This performance was significantly better
      than using spikes or LFPs alone. These results, together with our previous
      findings, suggest that a single decoder based on both spikes and LFPs in PRR can
      robustly provide the subjects' motor intent under varying contexts for neural
      prosthetic applications.

PMID- 21096621
TI  - Study of geometrical uncertainty stemming from different reconstruction
      procedures on the flow field for a peripheral bypass graft.
AB  - The geometry of conduits derived from in vivo image data is subject to
      acquisition and reconstruction errors. This results in a degree of uncertainty in
      defining the bounding geometry for a patient-specific anatomical conduit. The
      impact of the conduit geometry uncertainty should be considered with respect to
      haemodynamic clinically relevant measures that may alter the perception and
      evaluation of prognosis and diagnosis. These are commonly fluid mechanic stresses
      on or near the wall. Taking an example of a peripheral bypass graft
      configuration, we examine the effects of image threshold on the geometry.
      Thresholding approaches are chosen from the existing image segmentation community
      and are based on clustering schemes. Two novel methods are also introduced. The
      geometries are reconstructed using a partition-of-unity implicit function
      approach from the stack of segmented cross-sections that yields a piecewise
      linear triangulated mesh. Methods to quantify the differences resulting in the
      virtual model reconstruction from the different thresholding methods are based on
      the distance between the models and the surface mean curvature.

PMID- 21096622
TI  - Atlas-based segmentation of brain tumor images using a Markov random field-based
      tumor growth model and non-rigid registration.
AB  - We propose a new and clinically oriented approach to perform atlas-based
      segmentation of brain tumor images. A mesh-free method is used to model tumor
      induced soft tissue deformations in a healthy brain atlas image with subsequent
      registration of the modified atlas to a pathologic patient image. The atlas is
      seeded with a tumor position prior and tumor growth simulating the tumor mass
      effect is performed with the aim of improving the registration accuracy in case
      of patients with space-occupying lesions. We perform tests on 2D axial slices of
      five different patient data sets and show that the approach gives good results
      for the segmentation of white matter, grey matter, cerebrospinal fluid and the
      tumor.

PMID- 21096623
TI  - Novel detection strategy for abnormalities in WCE video clips.
AB  - Wireless Capsule Endoscopy (WCE) is a revolutionary technology that allows
      physicians to examine the patients whole gastrointestinal tract, especially the
      small intestine. However, reviewing capsule endoscopic video is a labor intensive
      task and very time consuming. In this paper we propose a novel method to detect
      key frames with abnormalities. It is based on the adaptive non-parametric corner
      detection approach using both the color and texture features. Real world patient
      videos including abnormal findings are adopted to evaluate the performance of the
      proposed method. The experimental results demonstrate that the proposed approach
      leads to the reduction of the number of frames in the WCE video without losing
      critical information.

PMID- 21096624
TI  - Characterization of border structure using fractal dimension in melanomas.
AB  - There are many characteristics that differentiate normal moles (nevi) from
      melanomas. One of them is their boundary irregularity, which can be quantified
      using Fractal Dimension. In this work, fractal dimension of normal moles and
      melanoma was computed using the box counting method. These measurements were used
      to train a linear decoder in order to predict the pathology. The average
      performance to discriminate normal moles from melanomas reached 85% giving some
      insights about the power of the fractal dimension as a candidate for automatic
      detection and diagnosis.

PMID- 21096625
TI  - Radiologist model for cardiac rest period determination based on fuzzy rule.
AB  - Image data acquisition for the coronary arteries is generally implemented during
      the diastole rest period, in order to suppress blurring due to cardiac movement.
      The purpose of this study is to improve the semi-automated application to
      determine the cardiac rest period based on fuzzy logic. The cardiac rest period
      from 25 subjects were determined based on their normalized cross-correlation of
      consecutive frame images as well as normalized frame number as the measured
      variables. The fuzzy set and membership are generated based on the measured
      variables from the radiologist's visual assessment. That visual assessment is
      also regarded as a gold standard for verification. The distance difference
      between the proposed method and visual assessment was analyzed. The fuzzy logic
      approach for cardiac rest period determination has no significant difference
      compared to the visual assessment (p>0.05) in terms of start frame and end frame.
      The algorithm could be extended easily in case of there are some necessary
      variables should be added to accommodate rest period definition from different
      radiologist.

PMID- 21096626
TI  - Closed angle glaucoma detection in RetCam images.
AB  - Closed/Open angle glaucoma classification is important for glaucoma diagnosis.
      RetCam is a new imaging modality that captures the image of iridocorneal angle
      for the classification. However, manual grading and analysis of the RetCam image
      is subjective and time consuming. In this paper, we propose a system for
      intelligent analysis of iridocorneal angle images, which can differentiate closed
      angle glaucoma from open angle glaucoma automatically. Two approaches are
      proposed for the classification and their performances are compared. The
      experimental results show promising results.

PMID- 21096627
TI  - Towards automatic detection of age-related macular degeneration in retinal fundus
      images.
AB  - Age-related macular degeneration (AMD) is a leading cause of blindness worldwide.
      The disease is highly associated with age, and becoming increasingly prevalent in
      our aging societies. Drusen is a pathological feature that is well-associated
      with AMD. In this paper, we present a method of detecting drusen in retinal
      fundus images. The method first determines the location of the macula, which is
      used as a landmark for a clinical drusen grading overlay. Subsequently, regions
      of drusen are identified though a maximal region-based pixel intensity approach
      via RGB and HSV channels. Methods of reducing the effect of retinal and choroidal
      vessels are also described. The system is tested on a sample set of 16 fundus
      images from a clinical study, with half having drusen. Experiments on the results
      show a sensitivity and specificity of 0.75 on the test image set.

PMID- 21096628
TI  - Symbolic learning supporting early diagnosis of melanoma.
AB  - We present a classification analysis of the pigmented skin lesion images taken in
      white light based on the inductive learning methods by Michalski (AQ). Those
      methods are developed for a computer system supporting the decision making
      process for early diagnosis of melanoma. Symbolic (machine) learning methods used
      in our study are tested on two types of features extracted from pigmented lesion
      images: coloristic/geometric features, and wavelet-based features. Classification
      performance with the wavelet features, although achieved with simple rules, is
      very high. Symbolic learning applied to our skin lesion data seems to outperform
      other classical machine learning methods, and is more comprehensive both in
      understanding, and in application of further improvements.

PMID- 21096629
TI  - An open data mining framework for the analysis of medical images: application on
      obstructive nephropathy microscopy images.
AB  - This paper presents an open image-mining framework that provides access to tools
      and methods for the characterization of medical images. Several image processing
      and feature extraction operators have been implemented and exposed through Web
      Services. Rapid-Miner, an open source data mining system has been utilized for
      applying classification operators and creating the essential processing
      workflows. The proposed framework has been applied for the detection of salient
      objects in Obstructive Nephropathy microscopy images. Initial classification
      results are quite promising demonstrating the feasibility of automated
      characterization of kidney biopsy images.

PMID- 21096630
TI  - Context-based interpolation of 3-D medical images.
AB  - A context-based 3D interpolation technique is proposed to enhance the out-of
      plane resolution of 3D medical images. The proposed technique represents a new
      approach of aiding 3D interpolation and improving its performance by efficient
      use of domain knowledge about the anatomy, objects and imaging modalities. In the
      new approach a family of adaptive 3D interpolation filters are designed and
      conditioned on different spatial contexts (classes of feature vectors). Training
      is used to incorporate the domain knowledge into the design of these
      interpolators. Experimental results show significant improvement of the new
      approach over some existing 3D interpolation techniques.

PMID- 21096631
TI  - The Fitzhugh-Nagumo model: Firing modes with time-varying parameters & parameter
      estimation.
AB  - In this paper, we revisit the issue of the utility of the FitzHugh-Nagumo (FHN)
      model for capturing neuron firing behaviors. It has been noted (e.g., see [6])
      that the FHN model cannot exhibit certain interesting firing behaviors such as
      bursting. We illustrate that, by allowing time-varying parameters for the FHN
      model, one could overcome such limitations while still retaining the low order
      complexity of the FHN model. We also highlight the utility of the FHN model from
      an estimation perspective by presenting a novel parameter estimation method that
      exploits the multiple time scale feature of the FHN model, and compare the
      performance of this method with the Extended Kalman Filter through illustrative
      examples.

PMID- 21096632
TI  - Application of a null-beamformer to source localisation in MEG data of deep brain
      stimulation.
AB  - In this paper, we present an analysis of magnetoencephalography (MEG) signals
      from a patient with whole-body chronic pain in order to investigate changes in
      neural activity induced by DBS. The patient is one of the few cases treated using
      DBS of the anterior cingulate cortex (ACC). Using MEG to reconstruct the neural
      activity of interest is challenging because of interference to the signal from
      the DBS device. We demonstrate that a null-beamformer can be used to localise
      neural activity despite artefacts caused by the presence of DBS electrodes and
      stimulus pulses. We subsequently verified the accuracy of our source localisation
      by correlating the predicted DBS electrode positions with their actual positions,
      previously identified using anatomical imaging. We also demonstrated increased
      activity in pain-related regions including the pre-supplementary motor area,
      brainstem periaqueductal gray and medial prefrontal areas when the patient was in
      pain compared to when the patient experienced pain relief.

PMID- 21096633
TI  - Predicting lower limb muscular activity during standing and squatting using
      spikes of primary motor cortical neurons in monkeys.
AB  - In this study, we investigated predicting lower limb muscular activities of
      monkeys during standing and squatting motions using neuronal spikes in primary
      motor cortex M1. Finite impulse response models were built for prediction. Acute
      electrode arrays were used to collect neuronal spikes in the lower limb
      representation area of M1 in the left hemisphere, and electrodes were implanted
      to the right leg muscles to collect EMG signals. Multiple regions of the lower
      limb representation area of M1 were explored. The neurons from two common regions
      demonstrated high predictive power on all 6 investigated right leg EMG signals.
      This study shows that the cortical neuronal spikes can be used to predict lower
      limb muscular activities with high accuracy, and identifies regions of high
      predictive power, where chronic electrodes can be implanted for future brain
      machine interface applications.

PMID- 21096634
TI  - Estimating sparse Volterra models using group L1-regularization.
AB  - Sparse Volterra model (sVM) is defined as a Volterra model (VM) that contains
      only a subset of its all possible model coefficients corresponding to its
      significant inputs and the existing terms of those inputs. Compared with ordinary
      VM, sVM is more efficient and interpretable in representing sparsely connected
      multiple-input systems, e.g., neuronal networks. In this paper, we formulate a
      rigorous statistical method of estimating sVM based on the group L1
      regularization. It allows simultaneous selection and estimation of the
      significant groups of coefficients of a VM and results in a sVM. Simulation
      results show that the actual structure of a sVM can be faithfully recovered even
      with short input-output data. This method can be extended and applied to the
      identification of the functional connectivity between neurons.

PMID- 21096635
TI  - System identification of local field potentials under deep brain stimulation in a
      healthy primate.
AB  - High frequency (HF) Deep Brain Stimulation (DBS) in the Sub-Thalamic Nucleus
      (STN) is a clinically recognized therapy for the treatment of motor disorders in
      Parkinson Disease (PD). The underlying mechanisms of DBS and how it impacts
      neighboring nuclei, however, are not yet completely understood.
      Electrophysiological data has been collected in PD patients and primates to
      better understand the impact of DBS on STN and the entire Basal Ganglia (BG)
      motor circuit. We use single unit recordings from Globus Pallidus, both pars
      interna and externa segments (GPi and GPe) in the BG, in a normal primate before
      and after DBS to reconstruct Local Field Potentials (LFPs) in the region. We then
      use system identification techniques to understand how GPe LFP activity and the
      DBS signal applied to STN influence GPi LFP activity. Our models suggest that
      when no stimulation is applied, the GPe LFPs have an inhibitory effect on GPi
      LFPs with a 2-3 ms delay, as is the case for single unit neuronal activity. On
      the other hand, when DBS is ON the models suggest that stimulation has a dominant
      effect on GPi LFPs which mask the inhibitory effects of GPe.

PMID- 21096636
TI  - Mirrored high gamma cortical activity during finger tap imitation.
AB  - The discovery of mirror neuron system in the macaque study in the 1990s explored
      a new way to investigate motor imitation. By using the electrocorticographic
      (ECoG) with high resolution in both spatial and temporal domains, this paper
      studies brain function during both observation and execution of a simple finger
      tapping task. Four epilepsy patients were asked to watch simple finger tapping
      video clips and then imitate the same action themselves. A significant mirrored
      power increase in the high gamma (HG) band (> 60Hz) have been observed over the
      superior parietal cortex in the right hemisphere. Furthermore, the power changes
      in the frequency range 75-95Hz were phase locked to the finger tapping
      trajectory. The temporal patterns of ECoG power varied during observation and
      execution, and were similar with the neuronal firing histogram recorded in the
      macaque imitation study.

PMID- 21096637
TI  - Point process models show temporal dependencies of basal ganglia nuclei under
      deep brain stimulation.
AB  - Deep Brain Stimulation (DBS) is an effective treatment for patients with
      Parkinsons disease, but its impact on basal ganglia nuclei is not fully
      understood. DBS applied to the subthalamic nucleus (STN) affects neurons in the
      Globus Pallidus pars interna (GPi) through direct projections, as well as
      indirectly through the Globus Pallidus pars externa (GPe). Since traditional
      statistical analyses of electrophysiological data provide too coarse a view of
      circuit dynamics, and mesoscopic biophysical dynamic models contain an
      intractable number of state variables for small populations of neurons, we apply
      a modular approach and treat each region in the STN-GPe-GPi circuit as a multi
      input multi-output point process system. We use microelectrode recordings of a
      normal primate with DBS applied to STN at 100 and 130 Hz to estimate point
      process models (PPMs) for recorded regions in GPi. Our PPMs uncovered distinct
      dependencies between regions of GPe and GPi neurons, separated by the position of
      the GPi neurons, and showed normal refractory periods, inhibition from projecting
      neurons in the GPe, and DBS-induced oscillatory effects. The PPMs also showed the
      relative impact of the above factors, which traditional statistics fail to
      capture. Our PPM framework suggests a useful approach for understanding dynamics
      of complex neural circuits.

PMID- 21096638
TI  - A biologically plausible model for same/different discrimination.
AB  - Abstract rules can be learned by several species (not only humans). We propose a
      biologically plausible model for same/different discrimination, that can point
      towards the neural basis of abstract concept learning. By including a neural
      adaptation mechanism to a discriminator model formerly introduced in the
      literature, selective clusters of neurons fire depending on whether or not the
      stimuli compared are the same or not. These selective neurons are consistent with
      experimental findings in the literature. Moreover, reward and attention can
      modulate the relative strength of each attribute/feature of the stimulus, so more
      complex abstract discriminations can be achieved using the proposed model as a
      building block. As a formal model, it can be easily incorporated into several
      applications in robotics and intelligent machines.

PMID- 21096639
TI  - Differential stimulation of ON and OFF retinal ganglion cells: a modeling study.
AB  - A model of the electrophysiological properties of ON and OFF retinal ganglion
      cells (RGCs) was constrained and validated using experimental data from the
      literature. Our simulations support experimental findings that differences in the
      magnitude of the T-type Ca(2+) current explain differences in the intrinsic
      electrophysiology of ON and OFF RGCs. The models are used to investigate the
      potential for differential stimulation of ON and OFF RGCs during neuroprosthetic
      stimulation with sinusoidal current. The model predicts that OFF cells fire
      preferential over ON cells in a frequency band around 10 Hz.

PMID- 21096640
TI  - Statistical modelling of spike libraries for simulation of extracellular
      recordings in the cerebellum.
AB  - Brain machine interfaces with chronically implanted microelectrode arrays for
      signal acquisition require algorithms for successful detection and classification
      of neural spikes. During the design of such algorithms, signals with a priori
      known characteristics need to be present. A common way to establish such signals
      is to model the recording environment, simulate the recordings and store ground
      truth about spiking activity for later comparison. In this paper, we present a
      statistical method to expand the spike libraries that are used in a previously
      presented simulation tool for the purpose described above. The method has been
      implemented and shown to successfully provide quick access to a large assembly of
      synthetic extracellular spikes with realistic characteristics. Simulations of
      extracellular recordings using synthesized spikes have shown to possess
      characteristics similar to those of in-vivo recordings in the cat cerebellum.

PMID- 21096641
TI  - Energy expenditure during human gait. I - An optimized model.
AB  - Within the framework of multibody dynamics, a 3D large scale neuromusculoskeletal
      model of the human body is presented. To characterize the dynamics of skeletal
      muscle, a phenomenological model of energy expenditure was developed for
      estimating energy consumption during normal locomotion. Such model is able for
      predicting thermal and mechanical energy liberation under submaximal activation,
      muscle fiber type, and varying contractile conditions, typically observed in
      human motion. Future formulations of the indeterminate biomechanical problem,
      solved through the physiological criteria of minimization of metabolical cost of
      transport during gait, should consider the role of muscle groups in coordinating
      multijoint motion. Such an approach is presented in part II of the paper.

PMID- 21096642
TI  - A sEMG model with experimentally based simulation parameters.
AB  - A differential, time-invariant, surface electromyogram (sEMG) model has been
      implemented. While it is based on existing EMG models, the novelty of this
      implementation is that it assigns more accurate distributions of variables to
      create realistic motor unit (MU) characteristics. Variables such as muscle fibre
      conduction velocity, jitter (the change in the interpulse interval between
      subsequent action potential firings) and motor unit size have been considered to
      follow normal distributions about an experimentally obtained mean. In addition,
      motor unit firing frequencies have been considered to have non-linear and type
      based distributions that are in accordance with experimental results. Motor unit
      recruitment thresholds have been considered to be related to the MU type. The
      model has been used to simulate single channel differential sEMG signals from
      voluntary, isometric contractions of the biceps brachii muscle. The model has
      been experimentally verified by conducting experiments on three subjects.
      Comparison between simulated signals and experimental recordings shows that the
      Root Mean Square (RMS) increases linearly with force in both cases. The simulated
      signals also show similar values and rates of change of RMS to the experimental
      signals.

PMID- 21096643
TI  - Two-dimensional estimation of the electrohysterographic conduction velocity.
AB  - Propagation of action potentials (APs) through an adequate number of uterine
      muscle cells induces contraction of the uterus. Monitoring uterine contractions,
      as the first sign of labor, can provide important information on the course of
      pregnancy and delivery. Unfortunately, current monitoring methods are affected by
      serious limitations. The electrohysterogram (EHG), which is the noninvasive
      recording of the APs propagating through the uterine smooth muscle cells, is here
      analyzed as a potential alternative to current methods. We focus on estimating
      the conduction velocity (CV) of surface APs extracted from an EHG recorded in a
      multielectrode configuration. In this work, a two-dimensional, 64-channel, high
      density electrode grid is used. Maximum likelihood methods are employed for
      analyzing the EHG AP propagation in two dimensions. The use of different
      weighting strategies of the derived cost function is introduced to deal with poor
      interchannel signal similarity. The presented methods were evaluated by specific
      simulations proving the best weighting strategy to lead to an accuracy
      improvement of 58%. EHG measurements on women with uterine contractions confirmed
      the feasibility of the method by leading to values of conduction velocity within
      the expected physiological range.

PMID- 21096644
TI  - Real-time calculation of knee extension moment and its evaluation.
AB  - This paper proposes a real-time processing algorithm which estimates a subject
      knee moments using some joint angle data and EMGs of involved muscles. This
      algorithm will be essential part for the control system design of exoskeletal
      robotic devices. In order for this algorithm to accurately predict joint moments,
      it is necessary to know the one's musculo-skeletal properties, which is virtually
      impossible. An optimization process is used to determine one's musculo-tendon
      characteristics. The proposed method is evaluated through the comparison with
      experimental results.

PMID- 21096645
TI  - Real time BOLD functional MRI neuro-feedback affects functional connectivity.
AB  - Functional connectivity in the resting state based on BOLD functional MRI (fMRI)
      has been used mainly to observe brain networks while subjects 'do nothing'. The
      same principle, however, can be used for any other steady-state brain condition.
      In this study, we compared the connectivity of the motor area during simple
      finger tapping with and without real time neuro-feedback of the activation in the
      hand motor area. The presence of the neuro-feedback not only induces correlations
      between the visual and motor areas, but also increases basal ganglia involvement
      and bilateral motor cortex connectivity.

PMID- 21096646
TI  - Non-rigid registration of breast images using feature points.
AB  - We present a feature point detection algorithm which we use for non-rigid
      registration, illustrated for breast images (mammography, MRI). By associating
      the continuous intrinsic dimensionality of image structure with the output of a
      scale saliency algorithm, breast boundary points can be separated from internal
      feature points. Correspondences established for the breast boundary and internal
      feature points respectively are used to drive two recent non-rigid registration
      techniques: polyaffine transformation and coherent point drift registration.
      Experimental results are presented for digital breast tomosynthesis and 3D breast
      MRI, and in all case achieve good spatial alignments.

PMID- 21096647
TI  - Cephalometric landmarks identification using probabilistic relaxation.
AB  - In this paper, we develop methodology to locate cephalometric landmarks on X-ray
      images based on probabilistic relaxation, which combines local contextual
      information from the general shape of the bones of the head (used as measurements
      specific to each landmark in the form of its shape context) and relational
      information, expressing the relative position of the landmarks with respect to
      each other.

PMID- 21096648
TI  - Improvement in off-axis neuromuscular control through pivoting elliptical
      training: Implication for knee injury prevention.
AB  - The goal of this study was to investigate the efficacy of off-axis neuromuscular
      control training using a pivoting elliptical machine. Although knee motion is
      mainly in flexion/extension, injuries to the knee are usually associated with
      excessive off-axis movement (tibial axial rotation and valgus/varus). A pivoting
      elliptical training system was developed to improve neuromuscular control about
      the off-axes. Six week training was conducted in nine healthy individuals and
      seven healthy individuals served as control and only participated in evaluation
      sessions. Our results showed that following the pivoting elliptical training,
      individuals were able to reduce pivoting instability across different phases of
      the elliptical cycle (p<0.01) and also mediolateral instability at mid and
      terminal swing phase (p<0.05). A trend of reduced response time and phase
      dependent changes in EMG patterns were also observed. The results showed that the
      pivoting elliptical training is effective to improve off-axis neuromuscular
      control in healthy individuals and such training protocol can potentially be
      implemented to prevent knee injury.

PMID- 21096649
TI  - Robust outlier detection in high-density surface electromyographic signals.
AB  - High Density surface Electromyography (HDsEMG) has been applied in both research
      and clinical applications for non-invasive neuromuscular assessment in several
      different fields using 2-D array. Proper interpretation of HDsEMG signals
      requires identifying "good" channels (where there is no short-circuit or bad
      contact or major power line interference problem). Recording with many channels
      usually implies bad-contacts (that introduces large power line interference) and
      short-circuits (when using gels). In addition to online monitoring the electrode
      contact quality, it is necessary to identify "bad" channels, or outliers, prior
      to the analysis of HDsEMG signal. In this paper we introduce a robust method to
      identify outliers in a set of monopolar HDsEMG signals recorded from Biceps and
      Triceps Brachii, Anconeus, Brachioradialis and Pronator Teres. The sensitivity
      and precision of this method show that this approach is promising.

PMID- 21096650
TI  - Dynamic simulation of perturbation responses in a closed-loop virtual arm model.
AB  - A closed-loop virtual arm (VA) model has been developed in SIMULINK environment
      by adding spinal reflex circuits and propriospinal neural networks to the open
      loop VA model developed in early study [1]. An improved virtual muscle model
      (VM4.0) is used to speed up simulation and to generate more precise recruitment
      of muscle force at low levels of muscle activation. Time delays in the reflex
      loops are determined by their synaptic connections and afferent transmission back
      to the spinal cord. Reflex gains are properly selected so that closed-loop
      responses are stable. With the closed-loop VA model, we are developing an
      approach to evaluate system behaviors by dynamic simulation of perturbation
      responses. Joint stiffness is calculated based on simulated perturbation
      responses by a least-squares algorithm in MATLAB. This method of dynamic
      simulation will be essential for further evaluation of feedforward and reflex
      control of arm movement and position.

PMID- 21096651
TI  - Evaluation of motor unit placement algorithms for EMG simulation.
AB  - Motor unit layout algorithms have a significant effect on motor unit fibre
      densities recorded. Motor unit fibre densities are affected by both the method
      used to place the motor unit territories, and the mechanism by which muscle
      fibres are assigned to motor units. The first of these should emulate the process
      by which separate motor neurons create overlapping territories that cover the
      muscle cross section, while the second should have some relation to the processes
      involved with axonal arborization and development of the spatial dispersion of
      the neuro-muscular junctions. The success of an algorithm in creating
      physiologically realistic motor unit layouts may be evaluated, in part, by
      examining the distribution of the muscle fibres assigned to the motor units. This
      paper examines the motor unit fibre densities found in muscles created by two
      recent algorithms, and explores the degree to which the concepts used by these
      algorithms may be shared.

PMID- 21096652
TI  - Discrimination of EMG and acceleration measurements between patients with
      Parkinson's disease and healthy persons.
AB  - In this paper, we examine the potential of electromyographic (EMG) and
      acceleration measurements in discriminating patients with Parkinson's disease
      (PD) from healthy persons. Two types of muscle contractions are examined: static
      contractions of biceps brachii muscles and elbow extension movements. Twelve
      features are extracted from static and ten features from extension measurements.
      These features describe signal morphology and nonlinear characteristics, power
      spreading in EMG wavelet scalograms and spectral coherence. Principal component
      approach is applied separately for static and extension trial to reduce the
      number of features before discrimination. The discrimination between subjects is
      done in a two-dimensional space by applying cluster analysis to the best
      discriminating principal components. The discrimination power of the used method
      was estimated with EMG and acceleration data measured from 56 patients with PD
      and 59 healthy controls. In the cluster analysis, three clusters were formed: one
      cluster with most (85%) of the healthy persons and two clusters with 80% of
      patients. Patients were divided into two clusters based on their type of motor
      disability (problems during movement and/or static contraction). Discrimination
      results show that EMG and acceleration measurements are potential for
      discriminating patients with PD from healthy persons. Furthermore, they have
      potential in the objective clinical assessment of PD.

PMID- 21096653
TI  - A mixed FES/EMG system for real time analysis of muscular fatigue.
AB  - In this article, we present a functional electrical stimulator allowing the
      extraction in real time of M-wave characteristics from resulting EMG recodings in
      order to quantify muscle fatigue. This system is composed of three parts. A
      Labview software managing the stimulation output and electromyogram (EMG) input
      signal, a hardware part amplifying the output and input signal and a link between
      the two previous parts which is made up from input/output module (NIdaq USB
      6251). In order to characterize the fatigue level, the Continuous Wavelet
      Transform is applied yielding a local maxima detection. The fatigue is
      represented on a scale from 0 for a fine shaped muscle to 100 for a very tired
      muscle. Premilary results are given.

PMID- 21096654
TI  - A study on the forearm muscular reflexes during grasping for prosthetic
      applications.
AB  - Recently, there has been an increasing interest in upper-limb prosthetic hand
      control, but most of these studies focus on the detection of exact motion
      intentions. Therefore, the responses to unexpected disturbance are not taken into
      consideration. On the other hand, unimpaired people respond to external
      disturbances by reflexive responses, hence, it is important to explore how this
      kind of reactive responses could be applied into prosthetic hand applications,
      and whether it will improve the human-machine interaction in a dynamical way. Our
      objective for the present study was to examine the responses of the human
      reflexes on different conditions in order to apply them to our prosthetic hand.
      Electromyograph (EMG) signals were recorded from the forearm muscles of
      unimpaired people during grasping of a cylinder. Results showed that the reflexes
      have different tendencies depending on the direction on which the disturbance is
      applied.

PMID- 21096655
TI  - On the feasibility of learning to predict minimum toe clearance under different
      walking speeds.
AB  - A major concern in human movement research is preventing tripping and falling
      which is known to cause severe injuries and high fatalities in elderly (>65
      years) populations. Current falls prevention technology consists of active
      interventions e.g., strength and balance exercises, preimpact fall detectors, and
      passive interventions e.g., shower rails, hip protectors. However it has been
      found that these interventions with the exception of balance exercises do not
      effectively reduce falls risk. Recent work has shown that the minimum toe
      clearance (MTC) can be successfully monitored to detect gait patterns indicative
      of tripping and falling risk. In this paper, we investigate the feasibility of
      predicting MTC values of consecutive gait cycles under different walking speeds.
      The objective is two-fold, first to determine if end point foot trajectories can
      be accurately predicted and second, if walking speed is a significant parameter
      which influences the prediction process. The Generalized Regression Neural
      Networks and the Support Vector Regressor models were trained to predict MTC time
      series successively over an increasing prediction horizon i.e., 1 to 10 steps.
      Increased walking speeds resulted in increased MTC variability but no significant
      increase in mean MTC height. Root mean squared prediction errors ranged between
      2.2-2.6mm or 10% of the mean values of the respective test data. The SVM slightly
      outperformed the GRNN predictions (0.5%-2.1% better accuracy). Best prediction
      accuracies decreased by 0.5mm for a doubling of walking speed i.e., from 2.5 km/h
      to 5.5 km/h. The results are encouraging because they demonstrate that the
      technique could be applied to forecasting low MTC values and provide new
      approaches to falls prevention technologies.

PMID- 21096656
TI  - Neuromuscular properties of different spastic human joints vary systematically.
AB  - We quantified the mechanical abnormalities of the spastic wrist in chronic stroke
      survivors, and determined whether these findings were representative of those
      recorded at the elbow and ankle joints. System identification techniques were
      used to characterize the mechanical abnormalities of these joints and to identify
      the contribution of intrinsic and reflex stiffness to these abnormalities.
      Modulation of intrinsic and reflex stiffness with the joint angle was studied by
      applying PRBS perturbations to the joints at different joint angles over the
      range of motion. Age-matched healthy subjects were used as control.

PMID- 21096658
TI  - An EMG-based handwriting recognition through dynamic time warping.
AB  - In this paper, an electromyography (EMG)-based handwriting recognition method was
      proposed for a latent tendency of natural user interface. The subjects wrote the
      characters at a normal speed, and six channels of EMG signals were recorded from
      forearm muscles. The dynamic time warping (DTW) algorithm was used to eliminate
      the time axis variance during writing. The process for template making and
      matching was illustrated diagrammatically. The results showed that no more than
      ten training trials per character could make an accuracy of above 90%. The
      recognition performance was compared in three character sets: digits, Chinese
      characters and capital letters.

PMID- 21096657
TI  - A novel dynamic sensing of wearable digital textile sensor with body motion
      analysis.
AB  - This work proposes an innovative textile sensor system to monitor dynamic body
      movement and human posture by attaching wearable digital sensors to analyze body
      motion. The proposed system can display and analyze signals when individuals are
      walking, running, veering around, walking up and down stairs, as well as falling
      down with a wearable monitoring system, which reacts to the coordination between
      the body and feet. Several digital sensor designs are embedded in clothing and
      wear apparel. Any pressure point can determine which activity is underway.
      Importantly, wearable digital sensors and a wearable monitoring system allow
      adaptive, real-time postures, real time velocity, acceleration, non-invasive,
      transmission healthcare, and point of care (POC) for home and non-clinical
      environments.

PMID- 21096659
TI  - A foot drop correcting FES envelope design method using tibialis anterior EMG
      during healthy gait with a new walking speed control strategy.
AB  - Restoring walking functions will greatly improve the foot-drop patients' life
      quality. In this work, we sampled 10 healthy subjects' gait data when walking in
      4 different stride frequency overground and developed a dynamic Functional
      Electrical Stimulation (dFES) system for foot-drop patients' walk training, using
      the processed tibialis anterior (TA) muscle EMG signal. The data sampled under
      the new strategy can be used by FES system directly. And the dFES system can
      provide dynamic Pulse Width Modulation (PWM) FES serial according to the healthy
      subjects' TA EMG intensity features.

PMID- 21096660
TI  - A methodological study for the multifactorial assessment of motor adaptation:
      Integration of kinematic and neural factors.
AB  - The aim of this work was to design a multimodal approach for the investigation of
      the different factors Motor Learning involves (e.g. planning, execution,
      correction, ...). Attention was focused onto the issue of Motor Adaptation (MA),
      which takes place when learning of a partially (but not completely) new motor
      strategy is needed. We hereby present a report about the methodological set-up
      which has been developed and tested for the investigation of motor adaptation
      during repetitive pointing tasks. We exploited the potentialities of the combined
      use of electroencephalographic and motion analysis techniques to find possible
      relation between the activity of the central nervous system and the neuro-musculo
      skeletal one. The adaptation-related changes in oscillatory brain activity and
      movement kinematics were monitored during a visually-guided, feedback-controlled,
      sequence of pointing tasks. Our preliminary results suggest that the proposed
      protocol: (i) can discern modifications of brain activity in the alpha and beta
      frequency bands; (ii) is sensible to kinematic alterations; and, (iii), allows a
      quantitative evaluation of performance in terms of both final result and motor
      patterns. In this work we identified a bunch of possible neuro-motor biomarkers,
      which we propose as possible indicators of adaptation.

PMID- 21096661
TI  - Intrinsic, reflex and voluntary contributions to task-dependent joint stiffness.
AB  - Dynamic joint stiffness defines the dynamic relationship between the position of
      the joint and the torque acting about it. Joint stiffness consists of two
      components: intrinsic and reflex stiffness. Previous work from our lab has shown
      that subjects can alter their reflex stiffness voluntarily and independently of
      intrinsic stiffness. Numerous studies have investigated whether reflex stiffness
      is altered in a task-dependent fashion; however the results of these studies are
      inconclusive. We designed an experimental paradigm where subjects were faced with
      3 tasks: one task where joint stiffness aided subjects, a second where joint
      stiffness hindered the subjects and a third where joint stiffness had no effect.
      We found that subjects did not alter their joint stiffness to perform the
      different tasks. Rather, they performed the tasks by voluntarily producing the
      appropriate torque based on visual feedback. Thus, with the paradigm used in this
      study, reflex stiffness was not modulated in a task-dependent manner.

PMID- 21096662
TI  - Predicting losses of balance during upright stance: evaluation of a novel
      approach based on wearable accelerometers.
AB  - The study of postural sway during quiet stance has proved to be a useful approach
      to investigate the function of the balance system. Recent studies have suggested
      that providing information on postural sway to vestibular patients through
      biofeedback may improve their balance awareness and therefore reduce their risk
      of falling. One drawback common to these approaches is related to timing:
      informing a patient about current balance conditions may not allow enough time to
      react and avoid a fall. Here we propose a new technique for predicting relevant
      balance related events based on the recording of inertial information on trunk
      and thigh movement using wearable devices. We have developed a regressive model
      for the prediction of quiet stance dynamics of the center of body mass (CM),
      based on these sensory data. Our preliminary results show that, with careful
      signal processing, such approach may allow to learn quiet stance dynamics based
      on the inverted pendulum model and use it in predicting critical balance
      conditions with a few hundreds of milliseconds advance. When these predictions
      are then used for event-detection the system provides accurate results and is
      thus promising for the development of a fall prevention device.

PMID- 21096663
TI  - Electromyographic evaluation of muscle recovery after isometric fatigue.
AB  - Despite growing interest in the behavior of electromyographic signals during
      muscle fatigue, few studies investigate fatigue recovery. In this work, we use
      surface electromyographic signals to determine the recovery time after isometric
      fatigue of the biceps brachii muscle in 90 degrees  flexion of the non-dominant
      elbow. Sixty volunteers were arranged into six experimental groups. Experiments
      were performed in three stages: reference phase (REF), fatigue resistance phase
      (RES), and recovery phase (REC). An isometric exercise was performed during the
      RES stage. The time interval between the RES and REC stages was different for
      each experimental group: 1, 2, 4, 8, 24 and 48 hours. Surface electromyographic
      signals were acquired during each phase, and the following electromyographic
      variables were calculated for each phase: median frequency (MDF), root mean
      squared (RMS) value, and maximum voluntary contraction (MVC). The REF data were
      compared with the REC data using a paired Wilcoxon test. The results show that
      the MVC is recovered 2 hours after the exercise. The MDF seems not to be fully
      recovered after 48 hours, but displays an apparent recovery trend.

PMID- 21096664
TI  - Muscle activation improvement during treadmill training at ischemia rat.
AB  - This study is aimed to investigate the muscle activity changes, including fatigue
      effects and the symmetry of muscle activation between affected and unaffected
      sides during a 10-day body weight support treadmill training program using a
      focal ischemia rat hindlimb model. Our findings of the MPF drop after stroke
      might indicate fatigue effects due to the compensation loading share of the
      ipsilateral side muscle during locomotion and the increase of the symmetry index
      reflects abnormal coactivation synergies after the onset of stroke. The EMG
      parameters could provide information on the muscle activation pattern and
      fatigue. The recovery rate after stroke could be investigated with EMG parameters
      together with the behavioral score, and both were improved during and after the
      treadmill training.

PMID- 21096665
TI  - Detection of nocturnal hypoglycemic episodes using EEG signals.
AB  - Hypoglycemia (low blood glucose) or the fear of hypoglycemia constitutes a
      significant barrier to the achievement of good glycemic control in the insulin
      treated diabetic patients. By measuring physiological responses derived from EEG
      and analyzing these, we establish that hypoglycemia can be detected non
      invasively. From a clinical study of six children with type 1 diabetes (T1D),
      associated with hypoglycemic episodes at night, their centroid (centre of
      gravity) alpha frequency reduced significantly (P<0.001) and their centroid theta
      frequency increased significantly (P<0.02). The overall data were organized into
      a training set (3 patients) and a test set (another 3 patients) randomly
      selected. Using the optimal Bayesian neural network which was derived from the
      training set with the highest log evidence, the estimated blood glucose profiles
      produced a significant correlation (P<0.005) against measured values in the test
      set.

PMID- 21096666
TI  - Non-linear recurrence analysis of NREM human sleep microstructure discloses
      deterministic oscillation patterns related to sleep stage transitions and sleep
      maintenance.
AB  - Sleep is a dynamic process aimed at obtaining the required neurophysiological
      states at certain times, according to circadian and homeostatic needs and despite
      external or internal interfering stimuli. In this context, peculiar transient
      synchronized EEG patterns (TSEP) are supposed to play the main role in the
      building up of EEG synchronization and in the flexible adaptation against
      perturbations Our study aimed at disclosing and quantifying attractor driven,
      hidden periodicity or, conversely, chaotic oscillation patterns in the series of
      these TSEP related to sleep stage transitions and sleep maintenance. At first we
      devised a multistep algorithm, able to capture TSEP from EEG during sleep in 10
      healthy volunteers. The time series of TSEP were then analyzed according to the
      Recurrence Plot (RP). TSEP series showed to form a pseudo-periodic series which
      becomes progressively denser and more stable until steady slow wave NREM sleep is
      reached, but looses stability just before REM sleep starts. This suggests that
      deterministic oscillatory patterns maybe adequate descriptors of the balance
      between homeostatic needs for NREM sleep and REM sleep pressure, supported by
      different cortical neuronal populations interactions.

PMID- 21096667
TI  - Optimal pulse shapes for magnetic stimulation of fibers: An analytical approach
      using the excitation functional.
AB  - An analytical approach to threshold problems in functional magnetic stimulation
      of nerve and skeletal muscle fibers was recently proposed, framed in the concept
      of excitation functional. Three generations of available equipments for magnetic
      stimulation are briefly considered, stressing the corresponding pulse shape in
      the stimulation coils. Using the criterion of minimum energy dissipated in
      biological tissues, an optimal shape for a current pulse in the coil that
      produces a just threshold depolarization in a nerve or skeletal muscle fiber is
      found. The method can be further developed and applied to other threshold
      problems in functional electric stimulation.

PMID- 21096668
TI  - Histogram based quantification of spinal cord injury level using somatosensory
      evoked potentials.
AB  - This paper uses an entropy based metric to study the somatosensory evoked
      potential (SEP) in rodents afflicted with focal demyelination spinal cord injury
      (SCI). It has been shown that amplitude characteristics of the SEP signal are a
      strong indicator of the integrity of the spinal cord sensory pathways. Compared
      to conventional correlation based metrics, the metric used in this paper exploits
      the amplitude histogram of SEP signals to provide a robust assessment of the
      different degrees of demyelination in the spinal cord. Results are presented
      using actual SEP signals collected on rodents with various levels of SCI.

PMID- 21096669
TI  - EEG feature selection using mutual information and support vector machine: A
      comparative analysis.
AB  - The large number of methods for EEG feature extraction demands a good choice for
      EEG features for every task. This paper compares three subsets of features
      obtained by tracks extraction method, wavelet transform and fractional Fourier
      transform. Particularly, we compare the performance of each subset in
      classification tasks using support vector machines and then we select possible
      combination of features by feature selection methods based on forward-backward
      procedure and mutual information as relevance criteria. Results confirm that
      fractional Fourier transform coefficients present very good performance and also
      the possibility of using some combination of this features to improve the
      performance of the classifier. To reinforce the relevance of the study, we carry
      out 1000 independent runs using a bootstrap approach, and evaluate the
      statistical significance of the F(score) results using the Kruskal-Wallis test.

PMID- 21096670
TI  - A closed-loop brain computer interface for real-time seizure detection and
      control.
AB  - The worldwide prevalence of epilepsy is approximately 1%, and 25% of epilepsy
      patients cannot be treated sufficiently by available therapies. Brain stimulation
      with closed-loop seizure control has recently been proposed as an innovative and
      effective alternative. In this paper, a portable closed-loop brain computer
      interface for seizure control was developed and shown with several aspects of
      advantages, including high seizure detection rate (92-99% during wake-sleep
      states), low false detection rate (1.2-2.5%), and small size. The seizure
      detection and electrical stimulation latency was not greater than 0.6 s after
      seizure onset. A wireless communication feature also provided flexibility for
      subjects freeing from the hassle of wires. Experimental data from freely moving
      rats supported the functional possibility of a real-time closed-loop seizure
      controller.

PMID- 21096671
TI  - Implementation of an iPhone for characterizing Parkinson's disease tremor through
      a wireless accelerometer application.
AB  - Parkinson's disease represents a chronic movement disorder, which is generally
      proportionally to age. The status of Parkinson's disease is traditionally
      classified through ordinal scale strategies, such as the Unified Parkinson's
      Disease Rating Scale. However, the application of the ordinal scale strategy
      inherently requires highly specialized and limited medical resources for
      interpretation. An alternative strategy involves the implementation of an iPhone
      application that enables the device to serve as a functional wireless
      accelerometer system. The Parkinson's disease tremor attributes may be recorded
      in either an effectively autonomous public or private setting, for which the
      resultant accelerometer signal of the tremor can be conveyed wireless and through
      email to a remote location for data post-processing. The initial testing and
      evaluation of the iPhone wireless accelerometer application for quantifying
      Parkinson's disease tremor successfully demonstrates the capacity to acquire
      tremor characteristics in an effectively autonomous environment, while
      potentially alleviating strain on limited and highly specialized medical
      resources.

PMID- 21096672
TI  - Calculation of photon path changes due to scatter in Monte Carlo simulations.
AB  - Computation using Monte Carlo simulations is widely used for modelling the light
      tissue interaction. Despite this, many of the methods used for building such
      simulations are poorly described in the literature. In particular, a scheme for
      translating the scatter angles produced from a phase function into updated photon
      direction vectors is not explicitly reported. To address this, a method for
      calculating the change in photon direction following a scattering event is
      described, thus illuminating one of the fundamental 'building blocks' for
      researchers developing their own Monte Carlo models. The equations derived in
      this paper may be readily incorporated into applicable Monte Carlo program code.

PMID- 21096673
TI  - Flow behavior and applicability of models for different hemodynamic states.
AB  - Arterial behavior analysis requires an accurate and dynamic knowledge of the
      stimuli and reactions involved. Belonging parameters quantification is performed
      by a data acquisition process and the application of existing models. However, it
      turns essentially to analyze the adjustment degree of the aforementioned models
      in terms of the arterial tree. Blood flow behavior as well as wall shear rate and
      the arterial compliance are anatomic location dependent. The main objective of
      the present work is to analyze the existing functional relationships between
      arterial wall and blood flow, in a particular place (brachial artery), in order
      to asses the specific model applicability, in cases such Poiseuille or Womersley
      models. In addition, due to the characteristic of the study, gender differential
      dynamic responses will be evaluated.

PMID- 21096674
TI  - Linear parameter varying system based modeling of hemodynamic response to
      profiled hemodialysis.
AB  - This paper proposes a novel linear parameter varying (LPV) system to model the
      hemodynamic response of end-stage renal failure patients to profiled hemodialysis
      (PHD). Ultrafiltration rate (UFR) and dialysate sodium concentration (Na) are
      imposed as the control inputs and the model computes the relative blood volume
      (RBV), percentage change in heart rate (DeltaDHR(%)) and percentage change in
      systolic blood pressure (DeltaDSBP(%)) during the course of hemodialysis. Model
      parameters are estimated using least squares approach based on data collected
      from 12 patients where each patient underwent 4 profile hemodialysis sessions.
      Parameter identification based on four profiled sessions of the same patient
      revealed an average mean square error of 0.11 for RBV, 0.24 for DeltaDHR and 0.43
      for DeltaDSBP. The results provided a good model to estimate the individual
      patient's hemodynamic behavior during hemodialysis. The developed model can play
      a vital role in designing a robust control system to automatically regulate the
      UFR and Na while maintaining the hemodynamic variables within stable range.

PMID- 21096675
TI  - Cardiac output and stroke volume estimation using a hybrid of three Windkessel
      models.
AB  - Cardiac output (CO) and stroke volume (SV) are the key hemodynamic parameters to
      be monitored and assessed in ambulatory and critically ill patients. The purpose
      of this study was to introduce and validate a new algorithm to continuously
      estimate, within a proportionality constant, CO and SV by means of mathematical
      analysis of peripheral arterial blood pressure (ABP) waveforms. The algorithm
      combines three variants of the Windkessel model. Input parameters to the
      algorithm are the end-diastolic pressure, mean arterial pressures, inter-beat
      interval, and the time interval from end-diastolic to peak systolic pressure. The
      SV estimates from the three variants of the Windkessel model were weighted and
      integrated to provide beat-to-beat SV estimation. In order to validate the new
      algorithm, the estimated CO and SV were compared to those obtained through
      surgically implanted TransonicTM aortic flow probes placed around the aortic
      roots of six Yorkshire swine. Overall, estimation errors in CO and SV derived
      from radial ABP were 10.1% and 14.5% respectively, and 12.7% and 16.5% from
      femoral ABP. The new algorithm demonstrated statistically significant improvement
      in SV estimation compared with previous methods.

PMID- 21096676
TI  - Development of a system to measure local measurement conditions around textile
      electrodes.
AB  - The three main influence factors on the interface between textile electrode an
      skin are: temperature, contact pressure and relative humidity. This paper
      presents first results of a prototype, which measures these local measurement
      conditions around textile electrodes. The wearable prototype is a data
      acquisition system based on a microcontroller with a flexible sensor sleeve.
      Validation measurements included variation of ambient temperature, contact
      pressures and sleeve material. Results show a good correlation with data found in
      literature.

PMID- 21096677
TI  - Sensor calibration models for a non-invasive blood glucose measurement sensor.
AB  - A calibration model was developed for a noninvasive blood glucose sensor, to
      determine how the blood glucose data measured by this sensor is related to blood
      glucose data measured with laboratory capillary finger sticks and to corrupting
      noise. The variability of calibration models for different patients was analyzed
      as well as the dynamics of the non-invasive blood glucose sensor according to
      reference blood glucose measurements and corrupting noise.

PMID- 21096678
TI  - A study of forward problem of magnetoacoustic tomography with magnetic induction.
AB  - Magnetoacoustic tomography with magnetic induction (MAT-MI) is a recently
      introduced method for imaging electrical impedance properties, which integrates
      classic electrical impedance tomography and ultrasonic technique. In this paper,
      a new method is proposed to avoid the singularity of the divergence of Lorentz
      force on the interfaces between two kinds of medium. A two-dimensional model was
      used for computer simulation studies to evaluate the proposed theory. The sound
      source distribution and the characteristics of the radiated acoustic field were
      investigated under three types of stimulation. The numerical results were derived
      through finite element method, and theoretical analysis was also carried out,
      both of which confirm the validity of the proposed method.

PMID- 21096679
TI  - Experimental verification of contrast mechanism in Magnetic Resonance Electrical
      Impedance Tomography (MREIT).
AB  - Magnetic Resonance Electrical Impedance Tomography (MREIT) aims to produce cross
      sectional images of a conductivity distribution inside the human body with a
      spatial resolution of a few millimeters. Injecting currents into an imaging
      object at different directions, we measure induced internal magnetic flux
      densities using an MRI scanner. Conductivity images are reconstructed based on
      the relation between the induced magnetic flux density and conductivity. Though
      there have been theoretical and experimental MREIT studies to explain and
      validate its imaging method, understanding the contrast mechanism in MREIT could
      be difficult due to the complexity in associated mathematical expressions. In
      this paper, we explain the contrast mechanism by performing and analyzing a
      series of imaging experiments of stable conductivity phantoms. Placing a thin and
      hollow cylinder with holes around its side inside a saline tank, we could
      construct a conductivity phantom with a stable conductivity contrast between two
      regions inside and outside the cylinder. Images of induced magnetic flux
      densities show ramp structures of which slopes are determined by conductivity
      contrasts. From the experimental results, we summarize the contrast mechanism in
      MREIT for better designs of MREIT pulse sequences and data processing methods.

PMID- 21096680
TI  - Towards non-invasive EIT imaging of domains with deformable boundaries.
AB  - We investigate on the use of the Domain Embedding Method (DEM) for the forward
      modelling in EIT. This approach is suitably configured to overcome the model
      meshing bottleneck since it does not require that the mesh on the domain is
      adapted to the boundary surface. This is of crucial importance for, e.g.,
      clinical applications of EIT, as it avoids tedious and time-consuming (re
      )meshing procedures. The suggested DEM approach can accommodate arbitrary yet
      Lipschitz smooth boundary surfaces and is not limited to polygonal domains. For
      the discretisation purposes, we employ B-splines as they allow for arbitrary
      accuracy by raising the polynomial degree and are easy to implement due to their
      inherent piecewise polynomial structure. Numerical experiments confirm that a B
      spline discretization yields, similarly to conventional Finite Difference
      discretizations, increasing condition numbers of the system matrix with respect
      to the discretisation levels. Fortunately, multiresolution ideas based on B
      splines allow for optimal wavelet preconditioning.

PMID- 21096681
TI  - Electrical impedance tomography reconstruction using a monotonicity approach
      based on a priori knowledge.
AB  - Electrical Impedance Tomography(EIT) has been proposed as an alternative modality
      for breast imaging. Current EIT reconstruction algorithms are based in
      optimization procedures that aim to minimize the difference between the recorded
      data and a set of candidate scenarios. However, these methods produce images with
      diffused edges, as sharp structures are penalized by current regularization
      techniques. In this paper, a novel edge preserving EIT reconstruction method is
      proposed. This technique uses a priori information obtained from Breast Microwave
      Radar images to estimate the location of the dense breast regions. Then, the
      monotonicity of the impedance matrix of the collected data is used to reconstruct
      a profile of the tissue distribution in the breast region. The proposed method
      yielded promising results when applied to numeric phantoms generated from
      Magnetic Resonance Imaging datasets.

PMID- 21096682
TI  - A fisher information matrix interpretation of the NOSER algorithm in electrical
      impedance tomography.
AB  - In this paper, we employ the concept of the Fisher information matrix (FIM) to
      reformulate and improve on the "Newton's One-Step Error Reconstructor" (NOSER)
      algorithm. FIM is a systematic approach for incorporating statistical properties
      of noise, modeling errors and multi-frequency data. The method is discussed in a
      maximum likelihood estimator (MLE) setting. The ill-posedness of the inverse
      problem is mitigated by means of a nonlinear regularization strategy. It is shown
      that the overall approach reduces to the maximum a posteriori estimator (MAP)
      with the prior (conductivity vector) described by a multivariate normal
      distribution. The covariance matrix of the prior is a diagonal matrix and is
      computed directly from the Fisher information matrix. An eigenvalue analysis is
      presented, revealing the advantages of using this prior to a Gaussian smoothness
      prior (Laplace). Reconstructions are shown using measured data obtained from a
      shallow breathing of an adult human subject. The reconstructions show that the
      FIM approach clearly improves on the original NOSER algorithm.

PMID- 21096683
TI  - Polar decomposition radio-frequency current density imaging.
AB  - Polar Decomposition Radio-frequency Current Density Imaging (PD-RFCDI) is an
      imaging technique that non-invasively measures RF current density components
      inside a sample using MRI. Previous PD-RFCDI implementations suffer from the
      strict constraint on the amount of applied current as well as severe interference
      from the unwanted induced current. This work proposes solutions to both problems
      which successfully remove the current constraints of PD-RFCDI. Both simulation
      and experiment were used to verify the validity of PD-RFCDI on a clinical MRI
      scanner.

PMID- 21096684
TI  - Experimental demonstration of noncontact pulse wave velocity monitoring using
      multiple Doppler radar sensors.
AB  - In this paper, two Doppler radars are used to monitor the pulse movements at the
      heart and the calf in order to measure the pulse wave velocity (PWV) wirelessly.
      Both simulation and experiment have been performed to demonstrate the feasibility
      of the proposed noncontact PWV monitoring. A three-stage calibration procedure,
      including DC offset calibration, circuit delay calibration and antenna radiation
      pattern calibration, has been developed for reliable long-term PWV monitoring.
      The measurement results have been verified by wired contact measurement with
      pulse transducers.

PMID- 21096685
TI  - Preliminary characterization of a glucose-sensitive hydrogel.
AB  - We present proof-of-concept studies that display the potential for using a
      glucose-sensitive hydrogel as a continuous glucose sensor. A study to
      characterize the swelling ratio of the hydrogel at normal physiological and
      pathological hyperglycemic glucose levels was performed. The hydrogel exposed to
      the hyperglycemic glucose solution had a higher equilibrium swelling ratio than
      the hydrogel exposed to the normal glucose concentration solution. The
      diffusivity of a small molecule, fluorescein isothiocyanate (FITC), through a
      hydrogel exposed to a hyperglycemic solution was determined using fluorescence
      recovery after photobleaching (FRAP). The diffusivity was found to be 4.2 * 10(
      14) m(2)/s, a value approximately four orders of magnitude smaller than the
      diffusivity of FITC in glucose solution. The permeability of the hydrogel after
      equilibration in a hyperglycemic solution was found to be 5.1 * 10(-17) m(2), in
      the range of 2-4% agarose gels.

PMID- 21096686
TI  - Introducing knowledge of wearing compression stockings on the skin blood flow by
      using microHematron device.
AB  - The aim of this preliminary study was to review the actual state of knowledge
      concerning the mechanisms underlying compression medical stockings action on the
      skin blood flow (SBF) in capillaries. SBF was assessed by measuring the thermal
      conductivity of living-tissues using microHematron ambulatory device. The
      investigation was performed for different postures using three standard French
      classes (10-15 mmHg, 15-20 mmHg and 20-36 mmHg) of Medical compression stockings
      (MCS) on six healthy subjects without chronic venous insufficiency. The
      experiment was divided into four stages (supine, sitting, standing and walking)
      and was repeated for each class of compression stockings and without MCS. The
      results showed a significant improvement of SBF depending on the class of MCS
      used. Best results were obtained for the Class III, which exerts to the highest
      level of pressure exerted around the ankle. Due to the low number of subjects,
      which therefore reduces the statistical relevance of results, a non-significant
      difference in SBF due to the subject's posture was observed. Nonetheless, a
      positive action by all the classes of MCS on SBF was measured for the supine
      position. This is a very important result; with patients with chronic venous
      insufficiency have often some mobility reduction, MCS may enhance their
      microcirculation even at rest.

PMID- 21096687
TI  - Real time MRI prostate segmentation based on wavelet multiscale products flow
      tracking.
AB  - Currently, prostate cancer is the third leading cause of cancer-related deaths
      among men in North America. As with many others types of cancer, early detection
      and treatment greatly increases the patient's chance of survival. Combined
      Magnetic Resonance Imaging and Spectroscopic Imaging (MRI/MRSI) techniques have
      became a reliable tool for early stage prostate cancer detection. Nevertheless,
      their performance is strongly affected by the determination of the region of
      interest (ROI) prior to data acquisition process. The process of executing
      prostate MRI/MRSI techniques can be significantly enhanced by segmenting the
      whole prostate. A novel method for segmentation of the prostate in MRI datasets
      is presented. This method exploits the different behavior presented by signal
      singularities and noise in the wavelet domain in order to accurately detect the
      borders around the prostate. The prostate contour is then traced by using a set
      of spatially variant rules that are based on prior knowledge about the general
      shape of the prostate. The proposed method yielded promising results when applied
      to clinical datasets.

PMID- 21096689
TI  - Multiphase level set algorithm for coupled segmentation of multiple regions.
      Application to MRI segmentation.
AB  - Classic geometric active contour algorithms have the limitation of segmenting the
      image into only two regions: background and object of interest. A new multiphase
      level set algorithm for the segmentation of two or more regions of interest is
      proposed. This algorithm avoids by construction the presence of overlapped and
      void regions and no additional coupling terms are required. In addition, the
      number of iterations needed to reach convergence is small. The algorithm has been
      tested against a state-of-the-art multiphase method on both simulated and real
      Magnetic Resonance Imaging (MRI) volumes with favorable results.

PMID- 21096690
TI  - Intelligent artifact classification for ambulatory physiological signals.
AB  - Connected health represents an increasingly important model for health-care
      delivery. The concept is heavily reliant on technology and in particular remote
      physiological monitoring. One of the principal challenges is the maintenance of
      high quality data streams which must be collected with minimally intrusive,
      inexpensive sensor systems operating in difficult conditions. Ambulatory
      monitoring represents one of the most challenging signal acquisition challenges
      of all in that data is collected as the patient engages in normal activities of
      everyday living. Data thus collected suffers from considerable corruption as a
      result of artifact, much of it induced by motion and this has a bearing on its
      utility for diagnostic purposes. We propose a model for ambulatory signal
      recording in which the data collected is accompanied by labeling indicating the
      quality of the collected signal. As motion is such an important source of
      artifact we demonstrate the concept in this case with a quality of signal measure
      derived from motion sensing technology viz. accelerometers. We further
      demonstrate how different types of artifact might be tagged to inform artifact
      reduction signal processing elements during subsequent signal analysis. This is
      demonstrated through the use of multiple accelerometers which allow the algorithm
      to distinguish between disturbance of the sensor relative to the underlying
      tissue and movement of this tissue. A brain monitoring experiment utilizing EEG
      and fNIRS is used to illustrate the concept.

PMID- 21096688
TI  - Brain volume segmentation in newborn infants using multi-modal MRI with a low
      inter-slice resolution.
AB  - Brain volume segmentation from neonatal magnetic resonance images (MRI) offers
      the possibility of exploring the developmental changes, measuring the brain
      growth, detecting early disorders and three-dimensional (3D) volume
      reconstruction. However, such segmentation is challenging mainly due to the fast
      growth process, complex anatomy of the developing brain and often poor MRI
      quality. Existing techniques are mainly developed for adult brain and are not
      applicable to neonates or require additional corrections. In this paper we
      present an algorithm for brain volume segmentation in neonates using T1-weighted
      (T1-w) and T2-weighted (T2-w) MRI with a low inter-slice resolution. The method
      incorporates both intensity and edge information and consists of three main
      steps: image pre-processing, brain segmentation and 3D brain reconstruction. Our
      algorithm is tested on real neonatal brain MRI with a gestational age between 39
      41 weeks and achieves performance comparable to manual segmentation. Also,
      experimental segmentation results show that our method is effective and more
      accurate than segmentation methods originally developed for adults.

PMID- 21096691
TI  - Automatic detection of EEG artefacts arising from head movements.
AB  - The need for reliable detection of artefacts in raw and processed EEG is widely
      acknowledged. In this paper, we present the results of an investigation into
      appropriate features for artefact detection in the REACT ambulatory EEG system.
      The study focuses on EEG artefacts arising from head movement. The use of one
      generalised movement artefact class to detect movement artefacts is proposed.
      Temporal, frequency, and entropy-based features are evaluated using Kolmogorov
      Smirnov and Wilcoxon rank-sum non-parametric tests, Mutual Information Evaluation
      Function and Linear Discriminant Analysis. Results indicate good separation
      between normal EEG and artefacts arising from head movement, providing a strong
      argument for treating these head movement artefacts as one generalised class
      rather than treating their component signals individually.

PMID- 21096692
TI  - Fluctuating emg signals: investigating long-term effects of pattern matching
      algorithms.
AB  - In this paper, we investigate the behavior of state-of-the-art pattern matching
      algorithms when applied to electromyographic data recorded during 21 days. To
      this end, we compare the five classification techniques k-nearest-neighbor,
      linear discriminant analysis, decision trees, artificial neural networks and
      support vector machines. We provide all classifiers with features extracted from
      electromyographic signals taken from forearm muscle contractions, and try to
      recognize ten different hand movements. The major result of our investigation is
      that the classification accuracy of initially trained pattern matching algorithms
      might degrade on subsequent data indicating variations in the electromyographic
      signals over time.

PMID- 21096694
TI  - Dynamic channel selection to reduce computational burden in seizure detection.
AB  - Ambulatory physiological monitoring devices benefit patients, medical staff and
      hospitals by allowing patients to return home with the devices for monitoring.
      The main problem associated with designing such devices is that of power
      consumption. Wireless communications and complex processing are generally part of
      such devices and are power hungry components. These problems are magnified when
      dealing with EEG signals, with relatively high data rates, multiple channels, and
      advanced signal processing techniques required. This paper proposes a method to
      dynamically select EEG channels in the REACT seizure detection system based on
      information already available in the system, hence keeping any added
      computational complexity very low. Using the techniques computational effort can
      be reduced by up to 65% with no effect on the REACT seizure detection
      performance.

PMID- 21096693
TI  - Classification of protein profiles using fuzzy clustering techniques: an
      application in early diagnosis of oral, cervical and ovarian cancer.
AB  - Present study has brought out a comparison of PCA and fuzzy clustering techniques
      in classifying protein profiles (chromatogram) of homogenates of different tissue
      origins: Ovarian, Cervix, Oral cancers, which were acquired using HPLC-LIF (High
      Performance Liquid Chromatography-Laser Induced Fluorescence) method developed in
      our laboratory. Study includes 11 chromatogram spectra each from oral, cervical,
      ovarian cancers as well as healthy volunteers. Generally multivariate analysis
      like PCA demands clear data that is devoid of day-to-day variation, artifacts due
      to experimental strategies, inherent uncertainty in pumping procedure which is
      very common activities during HPLC-LIF experiment. Under these circumstances we
      demonstrate how fuzzy clustering algorithm like Gath Geva followed by Sammon
      mapping outperform PCA mapping in classifying various cancers from healthy
      spectra with classification rate up to 95 % from 60%. Methods are validated using
      various clustering indexes and shows promising improvement in developing optical
      pathology like HPLC-LIF for early detection of various cancers in all uncertain
      conditions with high sensitivity and specificity.

PMID- 21096695
TI  - SVM detection of epileptiform activity in routine EEG.
AB  - Routine electroencephalogram (EEG) is an important test in aiding the diagnosis
      of patients with suspected epilepsy. These recordings typically last 20-40
      minutes, during which signs of abnormal activity (spikes, sharp waves) are looked
      for in the EEG trace. It is essential that events of short duration are detected
      during the routine EEG test. The work presented in this paper examines the effect
      of changing a range of input values to the detection system on its ability to
      distinguish between normal and abnormal EEG activity. It is shown that the length
      of analysis window in the range of 0.5s to 1s are well suited to the task.
      Additionally, it is reported that patient specific systems should be used where
      possible due to their better performance.

PMID- 21096696
TI  - Wearable monitoring of lumbar spine curvature by inertial and e-textile sensory
      fusion.
AB  - This paper describes the design, the development and the preliminary testing of a
      wearable system able perform a real time estimation of the local curvature and
      the length of the spine lumbar arch. The system integrate and fuse information
      gathered from textile based piezoresistive sensor arrays and tri-axial
      accelerometers. E-textile strain sensing garments suffer from non-linearities,
      hysteresis and long transient, while accelerometers, used as inclinometers,
      present biased values and are affected by the system acceleration due to subject
      movements. In this work, focused on the wearability and comfort of the user, we
      propose a fusion of the information deriving from the two class of sensors to
      reduce their intrinsic errors affecting measurements. Comparative evaluation of
      system performances with stereophotogrammetric techniques shows a 2% error in
      lumbar arch length reconstruction.

PMID- 21096697
TI  - A new washable low-cost garment for everyday fall detection.
AB  - In this paper, a new garment for automatic fall detection and alert is presented
      for the first time. It includes a washable pullover with integrated acceleration
      sensors, evaluation and control electronics. The system measures the
      accelerations at the torso and on the arms in three directions in space. The fall
      detection is based on recognizing, by means of the sensors, the posture and
      abnormal acceleration magnitudes usually associated to a fall. The alarm as well
      as the movement information is sent via a wireless radio link. A fall will be
      detected within the pullover's electronics. The fall detection system was tested
      on ten volunteers. The daily life movements are also stored on a memory card. The
      latter can be read in on a PC. Thanks to an optimized production process, the
      system can be affordably reproduced in low volume productions and can be adjusted
      for any usage. The power supply of the system is realized with rechargeable
      batteries.

PMID- 21096698
TI  - Emerging low energy Wearable Body Sensor Networks using patch sensors for
      continuous healthcare applications.
AB  - Three emerging Wearable Body Sensor Networks (WBSN) using patch type sensors are
      examined and compared. Unique WBSN environment issues and techniques to overcome
      those issues are presented for continuous healthcare applications. The first is
      the battery powered RF patch sensor WBSN (Type 1); it maximizes user-convenience
      and is suitable for short-term healthcare. The second is the wirelessly powered
      patch sensor WBSN (Type 2); the proposed patch adopts Planar Fashionable Circuit
      Board (P-FCB) for pervasiveness and safety, and a base station controls an array
      of inductors that automatically configure sensor positions around the body. The
      Type 2 WBSN fits for long-term healthcare. Finally, a snap fastener patch sensor
      WBSN (Type 3) is proposed. This is the most secure method among 3. Again, P-FCB
      increases pervasiveness. A snap fastener provides secure power and data channels
      between sensors and a base station.

PMID- 21096699
TI  - Textile electrode straps for wrist-to-ankle bioimpedance measurements for Body
      Composition Analysis. Initial validation & experimental results.
AB  - Electrical Bioimpedance (EBI) is one of the non-invasive monitoring technologies
      that could benefit from the emerging textile based measurement systems. If
      reliable and reproducible EBI measurements could be done with textile electrodes,
      that would facilitate the utilization of EBI-based personalized healthcare
      monitoring applications. In this work the performance of a custom-made dry
      textile electrode prototype is tested. Four-electrodes ankle-to-wrist EBI
      measurements have been taken on healthy subjects with the Impedimed spectrometer
      SFB7 in the frequency range 5 kHz to 1 MHz. The EBI spectroscopy measurements
      taken with dry electrodes were analyzed via the Cole and Body Composition
      Analysis (BCA) parameters, which were compared with EBI measurements obtained
      with standard electrolytic electrodes. The analysis of the obtained results
      indicate that even when dry textile electrodes may be used for EBI spectroscopy
      measurements, the measurements present remarkable differences that influence in
      the Cole parameter estimation process and in the final production of the BCA
      parameters. These initial results indicate that more research work must be done
      to in order to obtain a textile-based electrode that ensures reliable and
      reproducible EBI spectroscopy measurements.

PMID- 21096700
TI  - The ear as a location for wearable vital signs monitoring.
AB  - Obtaining vital signs non-invasively and in a wearable manner is essential for
      personal health monitoring. We propose the site behind the ear as a location for
      an integrated wearable vital signs monitor. This location is ideal for both
      physiological and mechanical reasons. Physiologically, the reflectance
      photoplethysmograph (PPG) signal behind the ear shows similar signal quality when
      compared to traditional finger transmission PPG measurements. Ballistocardiogram
      (BCG) can be obtained behind the ear using 25mm*25mm differential capacitive
      electrodes constructed using fabric. The BCG signal is able to provide continuous
      heart rate and respiratory rate, and correlates to cardiac output and blood
      pressure. Mechanically, the ear remains in the same orientation relative to the
      heart when upright, thus simplifying pulse transit time calculations.
      Furthermore, the ear provides a discreet and natural anchoring point that reduces
      device visibility and the need for adhesives.

PMID- 21096701
TI  - bioLights: light emitting wear for visualizing lower-limb muscle activity.
AB  - Analysis of muscle activity by electrophysiological techniques is commonly used
      to analyze biomechanics. Although the simultaneous and intuitive understanding of
      both muscle activity and body motion is important in various fields, it is
      difficult to realize. This paper proposes a novel technique for visualizing
      physiological signals related to muscle activity by means of surface
      electromyography. We developed a wearable light-emitting interface that indicates
      lower-limb muscle activity or muscular tension on the surface of the body in real
      time by displaying the shape of the activated muscle. The developed interface
      allows users to perceive muscle activity in an intuitive manner by relating the
      level of the muscle activity to the brightness level of the glowing interface
      placed on the corresponding muscle. In order to verify the advantage of the
      proposed method, a cognitive experiment was conducted to evaluate the system
      performance. We also conducted an evaluation experiment using the developed
      interface in conjunction with an exoskeleton robot, in order to investigate the
      possible applications of the developed interface in the field of
      neurorehabilitation.

PMID- 21096702
TI  - Implementation of array sensor module for a radial artery tonometry.
AB  - In this study, we developed an array sensor module to measure pulse wave of
      radial artery. To measure pressure, this module contains 7 piezoresistive sensors
      of the size of 1*1 mm. This sensor module is composed of a PCB for bonding
      sensor, PCB guide for wiring, silicon guide to keep its shape while PDMS coating,
      and PDMS layer protect fragile sensor and wire while faithfully transmitting the
      pressure of the patient's skin to the sensor. To test characteristic of pressure
      sensors in the sensor module, intra-chamber pressure was raised in 20mmHg step
      from 60mmHg to 220mmHg. The coefficient of determinant was r(2)>0.999. When the
      radial artery's pulse wave with developed sensor module was measured, pulse wave
      is clearly detected. In this study, developed array sensor module is appropriate
      to measure pulse wave.

PMID- 21096703
TI  - Development of a wearable vital signs monitor for healthcare.
AB  - In development countries the vital signs data measurement normally is performed
      at hospitals or laboratories where patients remain under observation with many
      electrodes attached on the body. The integration of biomedical data acquisition
      systems and information technologies (IT) enables continuous real time monitoring
      of physiological data in daily life, which improves patient's medical care and
      medical research possibilities. To achieve this goal, the research and
      development of some wearable intelligent sensors, sensors miniaturization, signal
      processing, wireless transmission, and databases development for these vital data
      have been done. Our goal is to implement a wearable system that can be used in
      places located outside of hospitals and medical institutions coverage area. In
      this paper, we present the current stage of the project where some intelligent
      modules have been implemented and other are under construction. Preliminary
      results concerning Non-Invasive Blood Pressure (NIBP), ECG and wireless
      connection are also presented.

PMID- 21096704
TI  - A stretchable electrode array for non-invasive, skin-mounted measurement of
      electrocardiography (ECG), electromyography (EMG) and electroencephalography
      (EEG).
AB  - This paper reports a class of stretchable electrode array capable of intimate,
      conformal integration onto the curvilinear surfaces of skin on the human body.
      The designs employ conventional metallic conductors but in optimized mechanical
      layouts, on soft, thin elastomeric substrates. These devices exhibit an ability
      to record spontaneous EEG activity even without conductive electrolyte gels, with
      recorded alpha rhythm responses that are 40% stronger than those collected using
      conventional tin electrodes and gels under otherwise similar conditions. The same
      type of device can also measure high quality ECG and EMG signals. The results
      suggest broad utility for skin-mounted measurements of electrical activity in the
      body, with advantages in signal levels, wearability and modes of integration
      compared to alternatives.

PMID- 21096705
TI  - A new system design of the multi-view Micro-Ball endoscopy system.
AB  - While the wireless endoscopic capsule examining human's large gastrointestinal
      (GI) cavity, such as stomach and large intestine, many interested spots are
      omitted by only one or two cameras due to its limited field of view. This paper
      proposes the new system architecture of the Micro-Ball for medical endoscopy
      application. Six cameras are embedded in the Micro-Ball for multiple fields of
      view, which can reduce endoscopic miss rate greatly. Based on this system
      architecture, a new working mode is proposed. The captured image data are saved
      in the Flash memory instead of being transmitted outside human body wirelessly.
      Only less than 6mJ is consumed when the Micro-Ball captures a frame of 480*480
      image and writes the image data into the Flash memory. The endoscopic Micro-Ball
      can work in human's GI tract for 10 hours when the image frame rate is 2 fps. The
      Micro-Ball endoscopy system is verified on the FPGA-based demonstration system.

PMID- 21096706
TI  - An RF-powered wireless multi-channel implantable bio-sensing microsystem.
AB  - An RF-powered wireless three-channel implantable bio-sensing microsystem is
      developed with blood pressure, EKG, and core body temperature sensing capability
      for untethered genetically engineered laboratory mice real-time monitoring. A
      flat silicone blood pressure sensing cuff with a MEMS capacitive pressure sensor
      is employed to form a novel less-invasive blood pressure sensor, which avoids
      vessel occlusion, bleeding, and blood clotting associated with the conventional
      catheter-based sensors. The implantable microsystem can be powered by an
      adaptively controlled external RF energy source at 4 MHz to ensure a stable on
      chip power supply. The overall system dissipates 200 microW and achieves a blood
      pressure sensing resolution of 1 mmHg within 1 kHz bandwidth, an EKG sensing
      resolution of 7.4 bits, and a temperature sensitivity of 19 mV/ degrees C
      measured from 22  degrees C to 43  degrees C. A prototype packaged sensor
      exhibits a weight of 495 mg, which is approximately 2% of a laboratory mouse body
      mass. On-going research effort is devoted to demonstrate in vivo performance in
      laboratory animals.

PMID- 21096707
TI  - Ligament imbalance metrics and an autonomous measurement system for post TKA.
AB  - This paper describes two useful metrics to estimate the ligament imbalance for
      post Total Knee Arthroplasty (TKA) scenario: the center of pressure and the net
      moments (varus-valgus and anterior posterior). Both metrics have been evaluated
      using high level models and experimental measurement. Self-powered analog and
      digital architectures for the center of pressure are elaborated here and complies
      with the Medical Implant Communication Service (MICS) standard. It is shown that
      the analog architecture is advantageous in terms of surface area and overall
      power consumption.

PMID- 21096708
TI  - A fully integrated preamplifier for cardiac sensing in a HV-CMOS technology.
AB  - A novel fully integrated preamplifier stage for cardiac activity sensing is
      presented. The proposed design takes advantage of the High Voltage CMOS (HV)
      technology properties to comply with the safety requirements of implantable
      devices without the addition of external decoupling capacitors. The power
      consumption is minimum; while the input referred noise is kept well below the
      minimum signal to be sensed. This first stage is a high pass filter with a cut
      off frequency at 75Hz, and 25db gain. Simulation results are presented, the
      circuit is being fabricated in a 0.6 microm technology.

PMID- 21096709
TI  - Implantable electronics: emerging design issues and an ultra light-weight
      security solution.
AB  - Implantable systems that monitor biological signals require increasingly complex
      digital signal processing (DSP) electronics for real-time in-situ analysis and
      compression of the recorded signals. While it is well-known that such signal
      processing hardware needs to be implemented under tight area and power
      constraints, new design requirements emerge with their increasing complexity. Use
      of nanoscale technology shows tremendous benefits in implementing these advanced
      circuits due to dramatic improvement in integration density and power dissipation
      per operation. However, it also brings in new challenges such as reliability and
      large idle power (due to higher leakage current). Besides, programmability of the
      device as well as security of the recorded information are rapidly becoming major
      design considerations of such systems. In this paper, we analyze the emerging
      issues associated with the design of the DSP unit in an implantable system. Next,
      we propose a novel ultra light-weight solution to address the information
      security issue. Unlike the conventional information security approaches like data
      encryption, which come at large area and power overhead and hence are not
      amenable for resource-constrained implantable systems, we propose a multilevel
      key-based scrambling algorithm, which exploits the nature of the biological
      signal to effectively obfuscate it. Analysis of the proposed algorithm in the
      context of neural signal processing and its hardware implementation shows that we
      can achieve high level of security with ~ 13X lower power and ~ 5X lower area
      overhead than conventional cryptographic solutions.

PMID- 21096710
TI  - Sub-cubic millimeter intraocular pressure monitoring implant to enable genetic
      studies on pressure-induced neurodegeneration.
AB  - There is often a strong correlation between elevated levels of intraocular
      pressure (IOP) and glaucoma; however, the underlying mechanisms that lead to
      blindness are not well understood. The key may lie in the study of genetic
      factors which determine IOP and lead to glaucoma-related blindness. Mice are
      typically used for genetic research due to their short generation time and
      accelerated lifespan, manageability, the availability of established and pure
      lines, and the ability to manipulate the genome. Post genetic manipulation, IOP
      monitoring at regular intervals is needed and for large scale testing, on the
      order of thousands of mice, it is crucial to have at least a partially automated
      data collection scheme. This work presents a fully wireless system on a chip that
      measures 300 um in its widest dimension, has a wireless microwave-based data and
      power link, and is capable of relaying digitized pressure recordings to a nearby
      base-station.

PMID- 21096711
TI  - Translating electromagnetic torque into controlled motion for use in medical
      implants.
AB  - A new propulsion method for sub-millimeter implants is presented that achieves
      high power to thrust conversion efficiency with a simple implementation. Previous
      research has shown that electromagnetic forces are a promising micro-scale
      propulsion mechanism; however the actual implementation is challenging due to the
      inherent symmetry of these forces. The presented technique translates torque into
      controlled motion via asymmetries in resistance forces, such as fluid drag. For a
      1-mm sized object using this technique, the initial analysis predicts that speeds
      of 1 cm/sec can be achieved with approximately 100 uW of power, which is about 10
      times more efficient than existing methods. In addition to better performance,
      this method is easily controllable and has favorable scalability.

PMID- 21096712
TI  - A high-power versatile wireless power transfer for biomedical implants.
AB  - Implantable biomedical actuators are highly desired in modern medicine. However,
      how to power up these biomedical implants remains a challenge since most of them
      need more than several hundreds mW of power. The air-core based radio-frequency
      transformer (two face-to-face inductive coils) has been the only non-toxic and
      non-invasive power source for implants for the last three decades [1]. For
      various technical constraints, the maximum delivered power is limited by this
      approach. The highest delivered power reported is 275 mW over 1 cm distance [2].
      Also, the delivered power is highly vulnerable to the coils' geometrical
      arrangement and the electrical property of the medium around them. In this paper,
      a novel rotating-magnets based wireless power transfer that can deliver ~10 W
      over 1 cm is demonstrated. The delivered power is significantly higher than the
      existing start-of-art. Further, the new method is versatile since there is no
      need to have the impedance matching networks that are highly susceptible to the
      operating frequency, the coil arrangement and the environment.

PMID- 21096713
TI  - Implantable micropump technologies for murine intracochlear infusions.
AB  - Due to the very small size of the mouse inner ear, 600 nL volume, developing
      effective, controlled infusion systems is quite challenging. Key technologies
      have been created to minimize both size and power for an implantable pump for
      murine intracochlear infusions. A method for coupling fine capillary tubing to
      microfluidic channels is presented which provides low volume, biocompatible
      interconnects withstanding pressures as high as 827 kPa (120 psi) and consuming
      less than 20 nL of volume exiting in-plane with the pump. Surface micromachined
      resistive bridges integrated into the flow channel for anemometry based flow rate
      measurement have been optimized for low power operation in the ultra-low flow
      rate regime. A process for creation of deformable diaphragms over pump chambers
      with simultaneous coating of the microfluidic channels has been developed
      allowing integration of a biocompatible fluid flow path. These advances represent
      enabling capabilities for a drug delivery system suitable for space constrained
      applications such as subcutaneous implantation in mice.

PMID- 21096714
TI  - Adaptive spike detection method based on capacitor arrays dedicated to
      implantable neural recording microsystems.
AB  - An analog spike detector circuit is presented, which adaptively generates a
      threshold level for spike detection based on hard-thresholding. Operation of the
      circuit was tested not only with a neural signal obtained from real in-vivo
      recording from a live animal, but also with a large sinusoidal baseline variation
      intentionally added to examine the capability of the circuit to track baseline
      variations as large as 50mV. The circuit runs at 3.3V supply voltage and
      dissipates 270 microW.

PMID- 21096715
TI  - New architecture for wireless implantable neural recording microsystems based on
      frequency-division multiplexing.
AB  - This paper investigates the use of a new architecture for implantable
      microsystems for multi-channel intra-cortical neural recording. The proposed
      architecture performs frequency-division multiplexing (FDM) to wirelessly
      transfer multiple neural channels to an external setup. Based on the proposed
      idea, an 8-channel wireless neural recording system was designed. As a result of
      FDM, preconditioned neural signals are placed in the frequency domain with 100kHz
      spacing, occupying a approximately 800-kHz bandwidth starting from 10MHz. The
      entire band is then shifted to within the traditional frequency modulation (FM)
      band. The system, designed in a 0.18-microm standard CMOS process, consumes
      4.7mW@1.8V.

PMID- 21096716
TI  - Thermal parameters measurement on fire fighter: improvement of the monitoring
      system.
AB  - Real time monitoring of the thermal parameters on firefighter when operating is
      one of the ProeTEX project goals. The newly developed equipments in the framework
      of this project, integrate one temperature sensor and one heat flux sensor in the
      rescuer's outer garment. The environment in which firefighters operate is
      dangerous and the thermal risks can occur everywhere. Consequently the heat flux
      is so not necessarily symmetrical. To improve the thermally at risk situation
      detection, a modified platinum sensors array was integrated in the jacket in
      order to monitor simultaneously heat flux and temperature surrounding the
      rescuer. The sensors were placed in the most exposed area (shoulders and chest)
      to monitor thermal parameter in different directions. The heat flux is calculated
      from the temperature difference. This sensors array enables the detection of
      temperature increases and heat flux even when the heat source is localized on one
      side.

PMID- 21096717
TI  - A novel device with 36 channels for imaging and signal acquisition of the
      gastrointestinal tract based on AC biosusceptometry.
AB  - The alternate current biosusceptometry (ACB) is a biomagnetic technique used to
      study some physiological parameters associated with gastrointestinal (GI) tract.
      For this purpose it applies an AC magnetic field and measures the response
      originating from magnetic marks or tracers. This paper presents an equipment
      based on the ACB which uses anisotropic magnetoresistive (AMR) sensors and an
      inexpensive electronic support. The ACB-AMR developed consists of a square array
      of 6*6 sensors arranged in a first-order gradiometer configuration with one
      reference sensor. The equipment was applied to capture magnetic images of
      different phantoms and to acquire gastric contraction activity of healthy rats.
      The results show a reasonable sensitivity and spatial-temporal resolution, so
      that it may be applied for imaging of phantoms and signal acquisition of the GI
      tract of small animals.

PMID- 21096718
TI  - Sensorized guidewires with MEMS tri-axial force sensor for minimally invasive
      surgical applications.
AB  - This paper describes the design of a tri-axial microelectromechanical force
      sensor (FS) that can be mounted on the tip of the guidewire. Piezoresistive
      silicon nanowires (SiNW) are embedded into a cross cantilever design with a
      manoeuvrable stylus to allow the detection of force in all directions. The
      electrical resistance changes in the four SiNWs are used to decode an arbitrary
      force applied onto the FS. The sensitivity of the device can be improved by two
      orders of magnitude compared to bulk Si thanks to the giant piezoresistive
      effects offered by the SiNW. Robustness of the FS is improved due to the novel
      design by incorporating a mechanical stopper at the tip of the stylus. Finite
      element analysis (FEM) analysis was used in designing the FS.

PMID- 21096719
TI  - Modelling and characterization of an instrumented medical needle in sight of new
      microsensor design for its insertion guidance.
AB  - A needle used in in-vivo medical percutaneous procedures is subject to auto
      deflection coming from its interactions with inhomogeneous and anisotropic
      tissues and organs in human body. In this paper we present the modelling and the
      characterization of microsensors glued on a medical needle in order to detect its
      real-time deflection by measuring strain variations on the needle. A first
      prototype has been developed by gluing metal foil strain gauges to the surface of
      a biopsy needle. The characterization of this prototype is carried out in
      comparison with theoretical analysis and finite element method (FEM) modelling.
      Results acquired through these different methods show an excellent conformity and
      confirm the feasibility of an instrumented medical device.

PMID- 21096720
TI  - Ultrasonically actuated silicon-microprobe-based testicular tubule metrology.
AB  - We report on a microfabricated silicon microprobe integrated with an ultrasonic
      actuator and polysilicon strain gauges for Microdissection Testicular Sperm
      Extraction (TESE) surgery. Multiple microprobe insertion experiments were
      performed on rat testis tissue and, by monitoring the tubule puncture artifacts
      in the force signal sensed by the microprobe, we were able to estimate the
      average diameter of the sperm-carrying tubules in the sample. We have
      demonstrated the ability to sense the existence of larger tubules embedded in a
      mass of thinner tubules, by means of an Area-Ratio based metric using an
      analytically calculated expression for the distribution of sizes measured by the
      microprobe. This information is important in microdissection TESE to distinguish
      tubules with and without fertile sperm, potentially eliminating the large
      incision currently required for optical spermatazoa localization.

PMID- 21096721
TI  - Single-cell stimulation and electroporation using a novel 0.18 u CMOS chip with
      subcellular-sized electrodes.
AB  - In drug screening and pharmaceutical research, high-throughput systems that are
      able to perform single-cell measurements are highly desired. Micro-electrode
      arrays try to answer this need but still suffer from significant drawbacks such
      as a small amount of electrodes and the inability to address single cells. Here,
      we present a novel multi-transistor array chip with 16,384 subcellular-sized
      electrodes based on 0.18 um CMOS technology. We show that single-cell stimulation
      is possible by applying voltage pulses on the electrode to stimulate the cells
      lying on top. Electroporation of the cell membrane is observed using the whole
      cell patch clamp technique and fluorescent dye-based live imaging. This
      technology could be used for high-throughput, single-cell manipulations for the
      purpose of large-scale drug screening and the investigation of fundamental cell
      processes.

PMID- 21096722
TI  - Development of nanostructured magnetic capsules by means of the layer by layer
      technique.
AB  - Nanomagnetic particles have been already taken into account as drug carriers
      thank to the possibility to control their movement to a specific location where
      the treatment is required by means of high gradient magnetic fields (HGMF). In
      this work the layer-by-layer technique (LbL) and nanomagnetic particles were used
      to developed innovative nanostructured magnetic capsules (NSMC). Their potential
      application as magnetic drug carriers was investigated under the influence of
      both static and oscillating magnetic fields used respectively to control capsule
      displacement and shell permeability. The assembly process of the nanostructured
      magnetic capsules, its characterization by Quartz Crystal Microbalance (QCM), and
      the results obtained under the influence of the magnetic fields are presented.

PMID- 21096723
TI  - Characterizing skin using a three-axis parallel drive force-sensitive micro
      robot.
AB  - There is a strong need to measure the complex mechanical properties of soft
      tissues such as skin. An in vivo experiment characterizing the mechanical
      response of human skin is presented. A rich set of deformations were applied to
      several positions on the arm using a novel force-sensitive micro-robot. All sites
      studied exhibit highly non-linear, anisotropic, and viscoelastic behavior. The
      experiments determined directions in which the skin response was stiffest. These
      directions agree with accepted orientations of Langer or relaxed skin tension
      lines.

PMID- 21096724
TI  - A linearized current stimulator for deep brain stimulation.
AB  - This paper develops the front end of the stimulator which is applied in the
      implantable deep brain stimulation (DBS) for the therapy of Parkinson's disease.
      This stimulator adopts the low power switched-capacitor DAC accompanying with
      voltage-to-current transconductance amplifiers to obtain the adjustable output
      currents. The proposed distortion cancellation technique improves the linearity
      of the current stimulator. Multiple transconductance amplifiers sharing a single
      DAC save the circuit area. The biphasic stimulation waveform is generated from
      the bridge switching technique and the programmable pulse. This stimulation
      circuit provides the 0 approximately 165 microA current for a typical loading of
      10 kOmega, 8 approximately 120 micros pulse width, and 126 approximately 244 Hz
      frequencies with a 0.35 microm CMOS technology at 3.3 V supply voltage.

PMID- 21096725
TI  - Heart rate detection from single-foot plantar bioimpedance measurements in a
      weighing scale.
AB  - Electronic bathroom scales are an easy-to-use, affordable mean to measure
      physiological parameters in addition to body weight. They have been proposed to
      obtain the ballistocardiogram (BCG) and derive from it the heart rate, cardiac
      output and systolic blood pressure. Therefore, weighing scales may suit
      intermittent monitoring in e-health and patient screening. Scales intended for
      bioelectrical impedance analysis (BIA) have also been proposed to estimate the
      heart rate by amplifying the pulsatile impedance component superimposed on the
      basal impedance. However, electronic weighing scales cannot easily obtain the BCG
      from people that have a single leg neither are bioimpedance measurements between
      both feet recommended for people wearing a pacemaker or other electronic
      implants, neither for pregnant women. We propose a method to detect the heart
      rate (HR) from bioimpedance measured in a single foot while standing on an
      bathroom weighting scale intended for BIA. The electrodes built in the weighing
      scale are used to apply a 50 kHz voltage between the outer electrode pair and to
      measure the drop in voltage across the inner electrode pair. The agreement with
      the HR simultaneously obtained from the ECG is excellent. We have also compared
      the drop in voltage across the waist and the thorax with that obtained when
      measuring bioimpedance between both feet to compare the possible risk of the
      proposed method to that of existing BIA scales.

PMID- 21096726
TI  - Dry electrode bio-potential recordings.
AB  - As wireless bio-medical long term monitoring moves towards personal monitoring it
      demands very high input impedance systems capable to extend the reading of bio
      signal during the daily activities offering a kind of "stress free", convenient
      connection, with no need for skin preparation. In particular we highlight the
      development and broad applications of our own circuits for wearable bio-potential
      sensor systems enabled by the use of an FET based amplifier circuit with
      sufficiently high impedance to allow the use of passive dry electrodes which
      overcome the significant barrier of gel based contacts. In this paper we present
      the ability of dry electrodes in long term monitoring of ECG, EEG and fetal ECG.

PMID- 21096727
TI  - Development of a data acquisition and analysis system for nociceptive withdrawal
      reflex and reflex receptive fields in humans.
AB  - A system for data acquisition and analysis of nociceptive withdrawal reflex (NWR)
      and reflex receptive field (RRF) is introduced. The system is constituted by
      hardware and software components. The hardware consists of devices commonly used
      for electrical stimulation and electromyographic and kinematic data recording.
      The software comprises two different programs: Wirex, a stand-alone program
      developed in LabView for data acquisition, and Reflex Lab, a Matlab-based toolbox
      for data analysis. These programs were developed to maximize the potential of the
      hardware, turning it into a complete stimulation system capable of automatic
      quantification of NWR and RRF. In this article, a brief review of NWR and RRF
      analysis is presented, the system features are described in detail and its
      present and future applications are discussed.

PMID- 21096728
TI  - Evaluation of a bimanual-coordinated upper-limbs training system based on the
      near infrared spectroscopic signals on brain.
AB  - Various rehabilitation systems have been developed to deliver therapy for
      hemiplegic patients. Fugl- Meyer scale and Motor Power Score were common used
      methods to evaluate training effect and validate the developed systems. However,
      these assessments were involved with some inevitable subjective factors of
      therapists. In order to objectively evaluate the effect of a bimanual training
      that performed with a novel self-controlled system, this paper carried out
      assessment based on cerebral activation and motion-tracking precision. Four
      healthy subjects coordinated the forces of two arms and performed motion tracking
      training in active-assisted and active-resisted modes. After training, movement
      performance was enhanced and the brain became more active with an increased
      cerebral activation. Experimental results verified the positive training effect
      of the new system and the correlation between the cerebral cortical activation
      and motion capability.

PMID- 21096729
TI  - Eye movement inhibits the facilitation of perceptual filling-in.
AB  - When a small figure is presented in human peripheral vision, it becomes invisible
      and invaded by surrounding texture, within a few seconds. This visual illusion is
      called perceptual filling-in. Time to filling-in (filling-in time) is varied by
      the properties of small figure, surround texture and some experimental
      conditions. In our preliminary study (Yokota, IEEE/IC-EMBS 2005), we found that
      incomplete fixation distributes filling-in time. Furthermore, that we can see
      nothing by restraining eye movement artificially is well known. Therefore, we can
      consider that filling-in time is influenced by eye movement. Although it has been
      recently reported that eye movement influences the filling-in occurrence
      (Martinez-Conde, Neuron 2006), the relation between eye movement and the filling
      in time has rarely been reported. For this study, we measured the filling-in time
      for three subjects, for four surrounding textures, with simultaneous recording of
      eye movement. The results show that the filling-in time correlates to the
      standard deviation of the power of the eye distance from the fixation point.
      Furthermore, we found relatively strong correlation between the filling-in time
      and the power of high frequency component 50-200 (Hz) in the eye movement, though
      the correlation of the power of low frequency component 10-50 (Hz) is not so
      high. Thus we suppose that filling-in is inhibited by small involuntary eye
      movement.

PMID- 21096730
TI  - Quantitative evaluation protocol for upper limb motor coordination analysis in
      patients with ataxia.
AB  - Objective and quantitative measurement is crucial in the definition of functional
      impairment and in the tracking of disease progress over time of patients affected
      by progressive pathologies, such as ataxia. A new experimental procedure for the
      quantitative description of upper limb movement and coordination analysis was
      developed by the integration of an optoelectronic system and dedicated electronic
      board with four visual and pressure stimuli. 20 passive retroreflective markers
      were placed on the subject's body and two types pointing tests were defined: in
      the first one, the subjects were asked to reach with the index finger five
      consecutive times each of the three targets ("repetitive test"), and in the
      second one, the subjects were asked to randomly reach the targets with the index
      finger ("random test"). The preliminary results showed that patients affected by
      ataxia took more time with a less smooth finger tip movement to perform the
      reaching tests when compared to healthy subjects. The velocity was lower and its
      profile was more irregular in ataxic subjects. The new developed experimental
      procedure seems to be very promising in the quantitative description of upper
      limb movements of pathological and healthy subjects and it seems to be able to
      distinguish the impairments due to different levels of ataxia.

PMID- 21096731
TI  - Multispectral transillumination imaging of skin lesions for oxygenated and
      deoxygenated hemoglobin measurement.
AB  - The early detection of melanoma is critical for patient survival. One of the
      indentifying features of new malignancy is increased blood flow to the lesion.
      Multispectral transillumination using the Nevoscope has been demonstrated to be
      an effective tool for imaging the sub-surface vascular architecture of skin
      lesions. Using multispectral images obtained from this tool in the visible and
      near-infrared range, as well as the relative difference in spectral absorption
      due to oxyhemoglobin and deoxyhemoglobin, we propose an empirical method to
      estimate the blood flow volume within a skin lesion. From the images, estimates
      of the distribution of both Hb and HbO(2) are calculated along with a ratiometric
      feature describing the relative oxygen saturation level in the blood. We validate
      our proposed method through the imaging of a skin phantom with embedded
      capillaries which can be filled with either an artificial Hb or HbO(2) liquid.
      Our near-IR, multispectral computations nicely differentiate the Hb filled
      phantom versus the HbO(2) filled phantom, demonstrating that these chromophores
      can be successfully separated and individually characterized for use in
      estimating the relative oxygen saturation of skin tissue.

PMID- 21096732
TI  - Positive contrast MRI of prostate brachytherapy seeds based on resonant frequency
      offset mapping.
AB  - MRI provides a safe, high-resolution imaging modality that can be used to assist
      physicians during intra-operative and post-operative phases of prostate
      brachytherapy. The metallic outer structure of brachytherapy seeds, however,
      naturally produces dark features in MR imagery, which can be confused with other
      image voids. This work explores the application of resonant frequency offset maps
      to predict the shift in resonant frequency that occurs in the vicinity of a
      metallic cylindrical seed-like object. An off-resonance imaging approach is then
      proposed to generate positive contrast markers that may aid in automatic
      unambiguous detection and localization of brachytherapy seeds in MR imagery.

PMID- 21096733
TI  - A decoupled circular-polarized volume head coil pair for studying two interacting
      human brains with MRI.
AB  - One of the major functions of the human brain is to mediate interactions with
      other people. Until recently, studying brain social interactions has not been
      possible due to the lack of measurable methods to observe two interacting minds
      simultaneously. We have developed a novel dual-head MRI coil that can scan two
      subjects' brains simultaneously while the subjects are socially interacting in
      one MRI scanner. Meanwhile, a novel scheme for decoupling two quadrature coils
      (not surface coils) is introduced and validated.

PMID- 21096734
TI  - A fourth gradient to overcome slice dependent phase effects of voxel-sized coils
      in planar arrays.
AB  - The signals from an array of densely spaced long and narrow receive coils for MRI
      are complicated when the voxel size is of comparable dimension to the coil size.
      The RF coil causes a phase gradient across each voxel, which is dependent on the
      distance from the coil, resulting in a slice dependent shift of k-space. A fourth
      gradient coil has been implemented and used with the system's gradient set to
      create a gradient field which varies with slice. The gradients are pulsed
      together to impart a slice dependent phase gradient to compensate for the slice
      dependent phase due to the RF coils. However the non-linearity in the fourth
      gradient which creates the desired slice dependency also results in a through
      slice phase ramp, which disturbs normal slice refocusing and leads to additional
      signal cancelation and reduced field of view. This paper discusses the benefits
      and limitations of using a fourth gradient coil to compensate for the phase due
      to RF coils.

PMID- 21096735
TI  - A desktop imaging system for teaching MR engineering.
AB  - This paper reports our results in developing a simple MRI system for teaching the
      basics of MR Engineering at the undergraduate or graduate level. LabVIEW data
      acquisition cards were used for generating and digitizing the RF signals and
      controlling gradients and transmit/receive and blanking switches. A very
      inexpensive and simple magnet reported previously by Sahakian was used to enable
      simple, projection reconstruction imaging. Students constructed the gradients, RF
      coils and did system level assembly and programming of the data acquisition
      system. At the end of the course students were tasked with identifying unknown
      imaging "phantoms" in their magnet, and then improving the image based on their
      knowledge.

PMID- 21096736
TI  - A novel spiral radiofrequency coil for high field mouse cardiac imaging.
AB  - The idea of a novel MR surface coil based on multi-turn spiral geometry is
      presented for use in mouse cardiac MRI. The benefits from flat, cylindrical
      arrangement of the coil are compared using computer simulations and MRI
      experiments in various cases of free space, phantom and animal loading
      conditions. Results show that the cylindrical case compares well with a
      commercially available birdcage coil offering a 50% signal intensity improvement
      for depths of penetration up to 6.1 mm from coil surface. There is also adequate
      B(1) field penetration that allows visualization of the lateral and inferior
      walls of the murine heart.

PMID- 21096737
TI  - A wavelet approach for on-line spike sorting in tetrode recordings.
AB  - A new method for spike sorting of tetrode recordings during data acquisition is
      introduced. For each tetrode channel, putative spikes are detected by means of a
      threshold, and then convolved with a cascade of wavelet filters. These
      transformed putative spikes are averaged and this average is used as a matched
      filter to find portions of signals that are likely to contain a spike. A
      collection of vectors containing the correlation coefficients between putative
      spikes and the matched filters is then clustered using K-Means. Centroids of the
      resulting clusters contain enough information to sort spikes recorded by all
      tetrode channels simultaneously. On-line sorting is achieved by measuring
      euclidean distance between putative new spikes and the cluster centroids.

PMID- 21096738
TI  - Combination of PCA and undecimated wavelet transform for neural data processing.
AB  - Nervous system conveys information by electrical signals called 'spikes',
      therefore, spikes detection and sorting are challenging topics in the neural data
      processing. The principal component analysis (PCA) is a convenient tool for
      clustering spikes; however it has some disadvantages for closely shaped and
      overlapped spikes. For such the cases, an algorithm based on the combination of
      the principal component analysis and undecimated wavelet transform, is proposed
      to enhance the cluster formation from the spikes mapping. These results indicate
      that the principal component analysis used in combination with the undecimated
      wavelet has a better performance in the spike sorting. This can lead to more
      compact and separate clusters in comparison with the PCA clustering and more
      efficient spike sorting.

PMID- 21096739
TI  - Extended Kalman filtering of point process observation.
AB  - A temporal point process is a stochastic time series of binary events that occurs
      in continuous time. In computational neuroscience, the point process is used to
      model neuronal spiking activity; however, estimating the model parameters from
      spike train is a challenging problem. The state space point process filtering
      theory is a new technique for the estimation of the states and parameters. In
      order to use the stochastic filtering theory for the states of neuronal system
      with the Gaussian assumption, we apply the extended Kalman filter. In this
      regard, the extended Kalman filtering equations are derived for the point process
      observation. We illustrate the new filtering algorithm by estimating the effect
      of visual stimulus on the spiking activity of object selective neurons from the
      inferior temporal cortex of macaque monkey. Based on the goodness-offit
      assessment, the extended Kalman filter provides more accurate state estimate than
      the conventional methods.

PMID- 21096740
TI  - Automatic classification of penicillin-induced epileptic EEG spikes.
AB  - Penicillin-induced focal epilepsy is a well-known model in epilepsy research. In
      this model, epileptic activity is generated by delivering penicillin focally to
      the cortex. The drug induces interictal electroencephalographic (EEG) spikes
      which evolve in time and may later change to ictal discharges. This paper
      proposes a method for automatic classification of these interictal epileptic
      spikes using iterative K-means clustering. The method is shown to be able to
      detect different spike waveforms and describe their characteristic occurrence in
      time during penicillin-induced focal epilepsy. The study offers potential for
      future research by providing a method to objectively and quantitatively analyze
      the time sequence of interictal epileptic activity.

PMID- 21096741
TI  - Combining ENG and EEG integrated analysis for better sensitivity and specificity
      of neuroprosthesis operations.
AB  - Combining non-invasive monitoring of action-related brain signals with the
      invasive recordings of the nerve motor output could provide robust natural and
      bidirectional multimodal Brain-Machine interfaces. One 26 years old, right-handed
      male who had suffered traumatic trans-radial amputation of the left arm was
      connected in a bidirectional way with a robotic hand prostheses. Cortical signals
      related with movement programming, execution, and feed-back were recorded by non
      invasive scalp electrodes to detect high-level information (i.e. onset of
      movement intention), while the efferent neural activity containing the low-level
      commands towards the missing limb was recorded from the amputated nerves by
      multipolar intra-neural electrodes. The aim of this article is to report advanced
      experiences aiming to investigate whether information on "hand-related"
      activities can be decoded by the combined analysis of motor-related signals
      simultaneously gathered via intraneural electrodes implanted into the peripheral
      nervous system and scalp recorded electroencephalography signals to govern a
      dexterous hand prosthesis using the natural neural "pathway".

PMID- 21096742
TI  - Combining computer and human vision into a BCI: can the whole be greater than the
      sum of its parts?
AB  - Our group has been investigating the development of BCI systems for improving
      information delivery to a user, specifically systems for triaging image content
      based on what captures a user's attention. One of the systems we have developed
      uses single-trial EEG scores as noisy labels for a computer vision image
      retrieval system. In this paper we investigate how the noisy nature of the EEG
      derived labels affects the resulting accuracy of the computer vision system.
      Specifically, we consider how the precision of the EEG scores affects the
      resulting precision of images retrieved by a graph-based transductive learning
      model designed to propagate image class labels based on image feature similarity
      and sparse labels.

PMID- 21096743
TI  - Decoding speed of imagined hand movement from EEG.
AB  - The kinematics of hand movement have been reported to be encoded in neural
      activities recorded at the primary motor cortex accompanying or immediately
      preceding the movement. In our earlier study, we demonstrated that the speed of
      imagined hand movements can be represented in the noninvasive EEG recordings and
      continuously decoded. In the present work, we aimed to systematically examine the
      spectral-temporal dynamics of imagination-related speed embedded in multiple
      frequency bands of EEG activity, including the alpha, beta and gamma bands and
      search for the optimal speed decoding for movement imagination.

PMID- 21096744
TI  - On the road to a neuroprosthetic hand: a novel hand grasp orthosis based on
      functional electrical stimulation.
AB  - To patients who have lost the functionality of their hands as a result of a
      severe spinal cord injury or brain stroke, the development of new techniques for
      grasping is indispensable for reintegration and independency in daily life.
      Functional Electrical Stimulation (FES) of residual muscles can reproduce the
      most dominant grasping tasks and can be initialized by brain signals. However,
      due to the very complex hand anatomy and current limitations in FES-technology
      with surface electrodes, these grasp patterns cannot be smoothly executed. In
      this paper, we present an adaptable passive hand orthosis which is capable of
      producing natural and smooth movements when coupled with FES. It evenly
      synchronizes the grasping movements and applied forces on all fingers, allowing
      for naturalistic gestures and functional grasps of everyday objects. The orthosis
      is also equipped with a lock, which allows it to remain in the desired position
      without the need for long-term stimulation. Furthermore, we quantify improvements
      offered by the orthosis compare them with natural grasps on healthy subjects.

PMID- 21096745
TI  - Signal quality classification for an ambulatory monitoring system.
AB  - A signal quality classification algorithm is presented to evaluate signal quality
      in ambulatory monitoring system. Acoustic based signal is classified as good
      signal, weak signal or noisy signal. Certain features in the acquired signal are
      extracted and analyzed to differentiate the class of signal quality. With this
      classification, wrong physiological estimation due to poor signal quality can be
      eliminated to avoid wrong conclusions and instructions in the ambulatory system.

PMID- 21096746
TI  - Validation of a transit time blood flow meter used for coronary bypass surgery.
AB  - The validation of a blood flow meter is presented. This flow meter is based on
      the transit time method that uses two ultrasound transducers and a reflector. The
      measuring is based on the time difference of the upstream and the downstream
      ultrasound transit time. The validation was based on the norm ANSI Std. N42.17A
      2003 of blood flow protocol. We used a flow simulator system with 3 mm pipe, bi
      distilled and desgasificated water as fluid. Flow simulator system uses a
      constant flow pump, regulated by a valve, and a peristaltic flow pump, regulated
      by a variable voltage source, like flow source through the pipe.

PMID- 21096747
TI  - Use of a gelatin cryogel as biomaterial scaffold in the differentiation process
      of human bone marrow stromal cells.
AB  - Biomaterials have been widely used in reconstructive bone surgery to heal
      critical-size long bone defects due to trauma, tumor resection, and tissue
      degeneration. In particular, gelatin cryogel scaffolds are promising new
      biomaterials owing to their biocompatibility; in addition, the in vitro
      modification of biomaterials with osteogenic signals enhances the tissue
      regeneration in vivo, suggesting that the biomaterial modification could play an
      important role in tissue engineering. In this study we have followed a biomimetic
      strategy where differentiated human bone marrow stromal cells built their
      extracellular matrix onto gelatin cryogel scaffolds. In comparison with control
      conditions without differentiation medium, the use of a differentiation medium
      increased, in vitro, the coating of gelatin cryogel with bone proteins (decorin,
      osteocalcin, osteopontin, type-I collagen, and type-III collagen). The
      differentiation medium aimed at obtaining a better in vitro modification of
      gelatin cryogel in terms of cell colonization and coating with osteogenic
      signals, like bone matrix proteins. The modified biomaterial could be used, in
      clinical applications, as an implant for bone repair.

PMID- 21096748
TI  - Viscoelastic behaviour of a small calibre vascular graft made from a POSS
      nanocomposite.
AB  - Small calibre (<6mm) polytetrafluoroethylene (PTFE) bypass grafts have poor
      medium and long term patency due to the development of neointimal hyperplasia at
      the distal anastomosis. The inelasticity of PTFE is implicated in this mechanism
      of failure. We have developed a novel polyhedral oligomeric silsesquioxane (POSS)
      nanocage incorporated into a poly(carbonate)urethane (PCU) biomaterial with
      enhanced biostability and improved antithrombogenicity making it ideal for
      cardiovascular applications. In this study the compliance and viscous component
      of a POSS-PCU small calibre graft was measured using a biomimetic pulsatile flow
      circuit and wall tracking ultrasound. A POSS-PCU graft displays elastic and
      viscous behaviour similar to the native artery. Furthermore, platelet adhesion
      and activation studies suggest POSS-PCU is a more biocompatible material than
      current industry favourite ePTFE. Alleviating the thrombogenicity of grafts and
      the mechanical mismatch between artery and graft is encouraging for the short and
      long term patency of the POSS-PCU graft.

PMID- 21096749
TI  - Textile-templated electrospun anisotropic scaffolds for tissue engineering and
      regenerative medicine.
AB  - Cardiovascular diseases, specifically myocardial infarction and end-stage heart
      failure represent some of the major pathologies that threaten human life. Here we
      present a novel approach for a bioactive cardiac patch based on a combination of
      biomedical and textile manufacturing techniques in concert with nano
      biotechnology based tissue-engineering stratagems. The technological goal is to
      create BioNanoTextilesTM (BNT) by using "conventional" fabrics as templates for
      creating three-dimensional nanofibrous scaffolds. Electrospinning nanofibrous
      scaffolds templated after "ordinary" textiles is a novel way to create complex
      patterned, 3-D scaffolds intrinsically mimicking some of the anisotropic
      structural features of the ventricular wall's extracellular matrix. In
      preliminary studies, we established that this approach will yield anisotropic 3-D
      scaffolds with mechanical properties dependent upon the yarn type of the textile
      templates. These scaffolds are biocompatible, as inferred from their support of
      H9C2 cardiac myoblast adhesion which promotes their proliferation as well as
      cardiac-like anisotropic organization. The use of textile manufacturing
      strategies will enhance the complexity of the 3-D scaffold structures and enable
      their commercialization, while providing an opportunity for the textile industry
      to advance established "low-tech" manufacturing technologies into the realm of
      "high-tech" BioNanoTextiles.

PMID- 21096750
TI  - Post-bioprinting processing methods to improve cell viability and pattern
      fidelity in heterogeneous tissue test systems.
AB  - Bioprinted tissue test systems show promise as a powerful tool for studying cell
      cell interaction in heterogeneous, tissue-like co-culture. Several challenges
      were encountered while attempting to consistently fabricate samples with high
      viability and pattern fidelity. This paper evaluates four methods for processing
      samples after bioprinting but prior to adding media for incubation. These
      methods, composed of various combinations of three techniques meant to promote
      cell hydration, are evaluated with respect to sample viability and pattern
      preservation. In the best performing method, Hank's Balanced Salt Solution was
      applied immediately after fabrication and a collagen overlayer was applied one
      hour thereafter. The success of this method highlights the ability of the
      collagen substrate to absorb moisture, which promotes cell health without
      disturbing the cell's printed location. An addendum to the main study is an
      investigation of the limits of an HP26 print cartridge to deposit cells at a
      faster rate for the purpose of creating cell layers with densities that approach
      confluence.

PMID- 21096751
TI  - Analysis of biomaterial latex-derived flow mechanical controller.
AB  - This paper describes the basic guidelines for developing an innovative biomedical
      device. It covers the issues of researching about a suitable material, developing
      a new device, and testing its proprieties to check its effectiveness. The goal of
      the device is to control food flow into the esophagus, reducing its volume and
      the speed of food intake to help in the treatment of obesity. This module, called
      Esophageal Flow Controller (EFC(r)), is made of latex. Three different models of
      prototypes were developed, and 10 units of each model had their constructive and
      mechanical characteristics evaluated. All of them have followed the same
      manufacturing cycle. The results showed that the Esophageal Flow Control module
      has all the essential characteristics of an effective device for flow control in
      the esophagus.

PMID- 21096752
TI  - Employment of a Healthgrid for evaluation and development of polysomnographic
      biosignal processing methods.
AB  - Longterm biosignal recordings, such as overnight sleep recordings (so-called
      polysomnographies, PSG), often vary in signal quality and signal shape. Movement
      artifacts occur frequently. This may impede successful application of automated
      processing algorithms designed for well-defined short-term recordings. To test
      existing algorithms on suitability for PSG analysis, and develop robust analysis
      tools, an environment that offers efficient application of biosignal methods on
      comprehensive and representative reference data is required. In this article, a
      Grid based biosignal processing platform is presented, that provides a large set
      of clinical PSG reference data collected within the SIESTA project. To date,
      different processing and evaluation methods with focus on polysomnographic
      electrocardiogram (PSG-ECG) based analysis are implemented. First results for
      heart rate analysis of PSG-ECG are given, including the introduction of a
      performance quality measure for non-annotated PSG-ECG. Different publicly
      available heart beat detection algorithms have been tested. As an example, the
      wqrs algorithm, provided by the PhysioNet shows a sensitivity of over 99% and a
      positive predictive value of over 94% on the PhysioNet's PSG reference data.
      Processed on the SIESTA data, it only detects around 60% of the heart beats,
      resulting in a low average performance quality of 0.28. Evaluation of further
      algorithms has led to the development of an improved, robust algorithm with a
      high average performance quality of 0.98.

PMID- 21096753
TI  - Automatic breath phase detection using only tracheal sounds.
AB  - While automatic distinction between the two breath phases
      (inspiration/expiration) can be done easily using lung sounds' intensity, it is
      challenging to do the same using only tracheal breath sounds. The current
      acoustic flow estimation methods use tracheal breath sounds to estimate the
      amount of flow and the onset of breath but also use lung sounds for respiratory
      phase identification. It would be advantageous to have an automatic and accurate
      method to identify breath phases from the tracheal signal. One may argue that
      given the alternation of respiratory phases, breath phase identification from
      tracheal sounds would be an easy task if one knows the first phase. However,
      during breathing, an event such as apnea, swallowing, or coughing may change the
      alternating nature of breath phases. In this study we have investigated several
      parameters derived from the phase duration, the shape of the sound envelope
      within each phase, and the sound's intensity in each phase, to develop a reliable
      method to differentiate between the two respiratory phases using only tracheal
      breath sounds. We used data from 6 healthy individuals, without any history of
      pulmonary diseases at 4 different flow levels (shallow, tidal, medium and very
      high). The most prominent features were found to be those derived from the
      duration, area and shape of the sound envelope in each phase. With a voting
      equation using the three most prominent features, our proposed method has shown
      an accuracy of 93.1% with sensitivity of 93.4% and specificity of 92.8% for
      breath phase identification without the need for assuming breath phase
      alteration.

PMID- 21096754
TI  - Cardiovascular and respiratory dynamics in patients with sleep apnea.
AB  - Sleep is an active and regulated process with restorative functions for physical
      and mental conditions. Based on recordings of brain waves and the analysis of
      characteristic patterns and waveforms it is possible to distinguish wakefulness
      and five sleep stages. Sleep and the sleep stages modulate autonomous nervous
      system functions such as body temperature, respiration, blood pressure, and heart
      rate. Methods of statistical physics are used to analyze heart rate and
      respiration to detect changes of the autonomous nervous system during sleep.
      Detrended fluctuation analysis and synchronization analysis and their
      applications to heart rate and respiration during sleep in healthy subjects and
      patients with sleep disorders are presented. The observed changes can be used to
      distinguish sleep stages in healthy subjects as well as to differentiate normal
      and disturbed sleep on the basis of heart rate and respiration recordings without
      direct recording of brain waves. Of special interest are the cardiovascular
      consequences of disturbed sleep because they present a risk factor for
      cardiovascular disorders such as arterial hypertension, cardiac ischemia, sudden
      cardiac death, and stroke.

PMID- 21096755
TI  - Detection of airway occlusion in simulated obstructive sleep apnea/hypopnea using
      ultrasound: an in vitro study.
AB  - Obstructive sleep apnea/hypopnea Syndrome (OSAHS) is the most common form of
      Sleep Disordered Breathing (SDB) and it is estimated to affect approximately 6%
      of US adult population. Various methods have been proposed for the development of
      inexpensive screening methods to detect SDB to reduce the need for costly
      nocturnal polysomnography (NPSG). By using the existing air in the airway as an
      ultrasonic contrast agent, we propose a method to examine the narrowing or
      occlusion of the airway associated with OSAHS events. We describe here an in
      vitro study that approximates the anatomical and acoustic characteristics of the
      airway and neck. In this experiment, we simulate the fully open airway as well as
      apnea and hypopnea events. These in vitro studies results show significant
      differences in the ultrasonic signals acquired from the open airway model versus
      those from the model depicting apnea and hypopnea events. Therefore, the findings
      provide a foundation for development of an ultrasound system to detect SDB in
      vivo.

PMID- 21096756
TI  - Converging micro-nano-bio technologies towards integrated in-vitro testing
      systems: Current activities and future challenges under the EU-Information &
      communication technologies program.
AB  - Interdisciplinary research towards integrated systems and their applications
      based on emerging convergence of information & communication technologies, micro
      nano and bio technologies is expected to have a direct impact in healthcare,
      ageing population and well being. Micro-Nano-Bio Systems (MNBS) research and
      development activities under the European Union's R&D Programs, Information &
      Communication Technologies priority address miniaturised, smart and integrated
      systems for in-vitro testing (e.g. lab-on-chips) and systems interacting with the
      human (e.g. autonomous implants, endoscopic capsules and robotics for minimally
      invasive surgery). Projects addressing in-vitro testing focus on research,
      development and testing of technology building blocs (e.g. sample preparation
      technique, ultra sensitive detection technique, chemistry process for molecular
      recognition and microfluidics) and their integration into smart and miniaturised
      systems e.g. DNA & protein arrays, biochips, Lab on Chip and Lab on Card. Current
      challenges and developed solutions as well as open issues to fully meet
      technological and socioeconomic needs are presented in this paper as background
      introductory information to the mini-symposium on "MNBS in-vitro testing".
      Relevant examples of R&D within the group will be presented in the mini
      symposium.

PMID- 21096757
TI  - Monolithically integrated biosensors based on Frequency-Resolved Mach-Zehnder
      Interferometers for multi-analyte determinations.
AB  - The application of fully monolithically-integrated Mach-Zehnder interferometer
      arrays fabricated by standard silicon technology to the label-free detection of
      analytes is introduced. Detection with the presented biosensor is based on a
      novel concept, the Frequency-Resolved Mach-Zehnder Interferometry (FR-MZI). In
      addition, a smart encapsulation based on an appropriately designed microfluidic
      system and performed at the wafer scale scheme for the easy delivery of the
      samples to be analyzed is demonstrated. Testing of the FR-MZI biosensors with
      model binding assays demonstrated the detection of streptavidin binding to
      immobilized biotin at concentrations in the sub nM range. This is the first
      experimental demonstration of the FR-MZI concept as well as the first
      demonstration of a monolithically fully-integrated MZI biosensor.

PMID- 21096758
TI  - Development of a toxin screening multi-parameter on-line biochip system
      'Toxichip'.
AB  - The development of a cell based biochip-sensing platform that examines the
      effects of toxic chemicals both electrically and optically is presented. The name
      of this sensing platform is called Toxichip. Toxichip aims to develop and promote
      alternative novel in-vitro testing methods for the monitoring of a vast array of
      toxins, thus alleviating the current demand for animal sacrifice while also
      permitting high throughput screening. Cell-based biosensors (CBBs), which treat
      living cells as sensing elements, are able to detect the functional information
      of biologically active analytes and also provide quantitative analysis. In
      general, they maintain living cells and observe the cellular physiological
      response after subjecting cells to toxin stimuli and verify the presence and the
      concentration of these stimuli. CBBs characterise with high sensitivity,
      excellent selectivity and a fast response time. There has been increased interest
      in the use of microelectronic biosensors that allow cellular activity to be
      analysed in vitro.

PMID- 21096759
TI  - Microfluidic and transducer technologies for lab on a chip applications.
AB  - Point-of-care diagnostic devices typically require six distinct qualities: they
      must deliver at least the same sensitivity and selectivity, and for a cost per
      assay no greater than that of today's central lab technologies, deliver results
      in a short period of time (<15 min at GP; <2h in hospital), be portable or at
      least small in scale, and require no or extremely little sample preparation.
      State-of-the-art devices deliver information of several markers in the same
      measurement.

PMID- 21096760
TI  - Humanitarian engineering: democratizing science and technology.
AB  - This paper is intended to mention some organizations detailing the type of
      activities being carried out and the action strategies; to analyze the situation
      in our country and, finally, to publicize our proposal to this problem.
      Capitalizing the experience gained in other parts of the world by different
      entities in order to promote the engineering humanitarian in our country,
      democratizing access to health, technology and the resources necessary to all the
      community, we will intend to promote that engineers and engineering students can
      take a part of the problem both domestically and worldwide, because we are part
      of the solution and we fit to take charge of the obligations as professionals and
      human beings.

PMID- 21096761
TI  - Group of R&D on biomedical engineering: Its development and results.
AB  - Conducting research and development activities generates new knowledge that can
      then be applied properly. In this sense, the groups of research and development
      on biomedical engineering (GRDBE) can contribute a lot in various areas such as
      teaching (theory and laboratory), as well as the development of prototypes, but
      mainly with the results they can provide. These contributions should response to
      specific needs of some sector, for example: health, environment, biology, and
      others. The present paper provides a description of the development of a GRDBE
      into a private university. Also, it's presented the amount of papers developed by
      this group and accepted by international congress on biomedical engineering (BE)
      on the 2007-2009 period. This paper also shows comparative charts with papers
      produced by other GRDBE that exist in our country, which are matter of analysis
      and conclusions.

PMID- 21096762
TI  - Automatic detection of tic activity in the Tourette Syndrome.
AB  - This study presents a simple decision-support system for the detection of tic
      events during the Tourette Syndrome (TS). The system is based on a triaxial
      accelerometer placed on the patient's trunk. TS is a neurological disorder that
      emerges during childhood and that is characterized by a large spectrum of
      involuntary/compulsive movements and sounds. 12 subjects with chronic TS
      participated in the study and the tic events were both measured by the proposed
      device and visually classified through video recording. 3D-acceleration
      timeseries were combined through a module operator and their noise was eliminated
      by a median filter. Signal to noise ratio was improved by a nonlinear energy
      operator. Finally, a time-variant threshold was used to detect tic events. The
      automatic tic recognition showed a performance around 80 % in terms of
      sensitivity, specificity and accuracy. In conclusion, this simple, automatic and
      unobtrusive method offers an alternative approach to quantitatively assess the
      tic events in clinical and non clinical environments. This overcomes the
      limitations of the current motor tic evaluation which is done by clinical
      observation and/or video-inspection in specialized neurological centres.

PMID- 21096763
TI  - Adaptive multi-infusion decision support for the multivariable circulatory
      management of critically ill patients.
AB  - We have developed a novel adaptive multi-infusion advisory system for circulatory
      management of critically ill patients which co-ordinates infusion adjustments to
      ensure safe trajectories. This system should reduce patient hospital stay and
      improve patient outcome by enhancing the quality of patient circulatory control;
      alleviating the clinical cognitive load, giving staff more time for direct
      patient care, while also reducing infusion adjustment errors. We have applied
      three derived circulatory variables which relate to the three main types of
      cardiovascular infusions (inotropic, vasoactive and fluid). A lumped parameter
      steady flow model of the human circulatory system and the effects of
      cardiovascular infusions was constructed for algorithm development, clinical
      experts providing feedback on a representative test set of simulated patients in
      circulatory shock. Independent self-learning fuzzy logic controllers (SLFLC) were
      found to give good adaptation to variable patient infusion sensitivities. A
      supervisory, rule-based module co-ordinates infusion adjustments to ensure safe
      circulatory trajectories. Monitoring of manual infusion adjustments allows timely
      advice and also a critiquing capability which can train junior staff and reduce
      infusion adjustment errors. A physical mock circulatory loop was used to
      construct and test our physical advisory system. Preliminary clinical results
      show good clinical utility of our adaptive multi-infusion advisory system.

PMID- 21096764
TI  - Intelligent shunt agent for gradual shunt removal.
AB  - When passive shunts, which divert cerebrospinal fluid (CSF) from the ventricles
      in the brain to another part of the body, were developed, apparently they change
      favourably the treatment of hydrocephalus, then it becomes of great importance to
      overcome the drawbacks of such shunts, and the gradual rising use of various
      shunts are accompanied by total shunt dependency with several problems and
      shortcomings has understandably become obvious among physicians as well as
      surgeons to rehabilitate and upgrade these shunts. There is a little use of
      carrying out arrested hydrocephalus which is subject to many aspects, ranging
      from problems of immediate clinical concern to the more unknowable areas of
      cerebrospinal fluid CSF dynamics, and it is not always as easy to define
      indications for arrested hydrocephalus or to evaluate the results of such
      treatment. However, it is important to attempt to define as precisely as possible
      a technique to measure the ability of arresting hydrocephalus, while current
      solutions estimations are based on long time procedure, evaluate parameters such
      as head growth, or ventricle sizes using CT or MRI scan. This paper proposes a
      new treatment approach and shunting system that helps improving diagnosis and
      treatment of Hydrocephalus patients. This approach suggests a developing and
      utilising an intelligent shunt agent (i-Shunt) that can learn from the patient's
      status and initiate a weaning program, and based on the response evaluation, the
      parameters of the shunt can be modified to accommodate the patient's needs.
      Therefore, a novel shunt could be build to satisfy the patient's need
      instantaneously by keeping the intracranial pressure (ICP) within normal levels,
      where it is actually directed toward shunt independency.

PMID- 21096765
TI  - A physiological model for extracorporeal oxygenation controller design.
AB  - Long term extracorporeal membrane oxygenation can be used in cases of severe lung
      failure to maintain sufficient gas exchange without the need to apply higher
      ventilation pressures which damage the lung additionally. The use of
      cardiopulmonary bypass devices is well established inside the operating room. The
      usage of such devices as long-term support in the intensive care unit is still
      experimental and limited to few cases. This is because neither machine
      architecture nor staff situation provides for the long term application scenario.
      In the joint research Project "smart ECLA" we target an advanced ECMO device
      featuring an automation system capable of maintaining gas concentrations
      automatically. One key requirement for systematic controller design is the
      availability of a process model, which will be presented in this article.

PMID- 21096766
TI  - Image-based red cell counting for wild animals blood.
AB  - An image-based red blood cell (RBC) automatic counting system is presented for
      wild animals blood analysis. Images with 2048*1536-pixel resolution acquired on
      an optical microscope using Neubauer chambers are used to evaluate RBC counting
      for three animal species (Leopardus pardalis, Cebus apella and Nasua nasua) and
      the error found using the proposed method is similar to that obtained for inter
      observer visual counting method, i.e., around 10%. Smaller errors (e.g., 3%) can
      be obtained in regions with less grid artifacts. These promising results allow
      the use of the proposed method either as a complete automatic counting tool in
      laboratories for wild animal's blood analysis or as a first counting stage in a
      semi-automatic counting tool.

PMID- 21096767
TI  - Computer aided surgery for percutaneous nephrolithotomy: Clinical requirement
      analysis and system design.
AB  - Percutaneous nephrolithotomy (PCNL) for the treatment of renal stones and other
      related renal diseases has proved its efficacy and has stood the test of time
      compared with open surgical methods and extracorporeal shock wave lithotripsy.
      However, access to the collecting system of the kidney is not easy because the
      available intra-operative image modalities only provide a two dimensional view of
      the surgical scenario. With this lack of visual information, several punctures
      are often necessary which, increases the risk of renal bleeding, splanchnic,
      vascular or pulmonary injury, or damage to the collecting system which sometimes
      makes the continuation of the procedure impossible. In order to address this
      problem, this paper proposes a workflow for introduction of a stereotactic needle
      guidance system for PCNL procedures. An analysis of the imposed clinical
      requirements, and a instrument guidance approach to provide the physician with a
      more intuitive planning and visual guidance to access the collecting system of
      the kidney are presented.

PMID- 21096768
TI  - Improvement of the health technology management process of the public Health
      Service in Morelos using the Six Sigma methodology.
AB  - The purpose of this study was to make a proposal to improve the management
      process of the health technology within the Health Service at Morelos State,
      Mexico, using the five stages of Six Sigma methodology: Definition, Measurement,
      Analysis, Improvement and Control. Up to date these five steps have been executed
      resulting in a set of proposals to improve the current health technology
      management process. This will allow the establishment of a medical equipment
      control program that impacts the three levels of Health Care Service in Morelos
      State in Mexico.

PMID- 21096769
TI  - Electrocardiographic T-wave peak-to-end interval for hypoglycaemia detection.
AB  - Electrocardiographic T wave peak-to-end interval (TpTe) is one parameter of T
      wave morphology, which contains indicators for hypoglycaemia. This paper shows
      the corrected TpTe (TpTe(c)) interval as one of the inputs contributing to detect
      hypoglycaemia. Support vector machine (SVM) and fuzzy support vector machine
      (FSVM) utilizing radial basis function (RBF) are used as the classification
      methods in this paper. By comparing with the classification systems using inputs
      of corrected QT interval (QT(c)) and heart rate only, the results indicate that
      the inclusion of TpTec in combination with QTc and heart rate performs better in
      the detection of hypoglycaemia in terms of sensitivity, specificity and accuracy.

PMID- 21096770
TI  - Classifier of intestinal contractile activity degree based on internal
      electroenterogram recording.
AB  - The study of the intestinal interdigestive motor migratory complex (IMMC) is
      relevant in gastroenterology because most of the gastrointestinal pathologies are
      reflected in anomalies of the IMMC. The aim of this work is to develop an
      automatic classifier to discriminate among the different intestinal contractile
      activity degrees (quiescence, irregular, and maximum contractile activity) that
      compound the IMMC from the internal recordings of electroenterogram. Spectral and
      statistical parameters estimated from the internal electroenterogram have been
      used as features to the classifiers based on Linear Discriminant Analysis (LDA)
      and linear Support Vector Machines (SVM). The accuracy obtained by the SVM
      classifier is slightly higher than that of the LDA classifier. An accuracy of
      around 91% was obtained for the binary SVM classifier (quiescence vs maximum
      activity) and around 74% for the multiclass one. The use of additional features,
      and non-linear SVM classifiers could yield better classification accuracy values.
      Nevertheless, preliminary results suggest that SVM classifiers could be a very
      helpful tool for automatic classification of intestinal contractile activity
      degrees and for the identification of the IMMC which could be used for diagnosing
      anomalies in the intestinal motor function.

PMID- 21096771
TI  - Detection of respiratory waveforms using non-contact electrodes during bathing.
AB  - The aim of this study is to develop a method for measuring the respiratory
      waveform using non-contact electrodes during bathing. To determine the most
      appropriate electrode arrangement, we modeled a composite system consisting of a
      body submerged in bath water. We calculated the frequency dependence of the
      impedance amplitude using a three-dimensional finite difference method (3D-FDM).
      The simulation results showed that an increase in chest size due to inspiration
      caused a decrease in the impedance amplitude in the frequency range of 0.1 Hz to
      1 MHz. Next, bioelectric impedance (BEI) was measured in the frequency range of 4
      kHz to 4 MHz at the maximum-end-expiration and maximum-end-inspiration stages.
      BEI results were consistent with those obtained from the model simulations. We
      found that 1 MHz was the appropriate frequency for measuring the respiratory
      waveform, and the time dependence of the impedance amplitude was measured at 1
      MHz. The impedance amplitude agreed well with the respiratory waveform obtained
      from rubber strain gauge plethysmography, which was used as a reference.

PMID- 21096772
TI  - Development of a point-of-care device for the quantification of bilirubin in
      cerebral spinal fluid.
AB  - In North America, an estimated 30,000 patients annually experience an aneurysmal
      subarachnoid hemorrhage (SAH). In approximately five percent of these patients,
      the hemorrhage is not visible on computerized tomography scans due to the
      inability to image blood at time intervals greater than 12 hours post symptom
      onset. For these patients (many of which have experience a sentinel hemorrhage
      that is a precursor to a more significant rupture) a method is needed for
      accurately analyzing cerebral spinal fluid (CSF) for evidence of SAH. Further, it
      is necessary to differentiate blood associated with the SAH from blood associated
      with the spinal tap procedure. This paper presents the development of a point-of
      care device that is capable of performing such an analysis. The stand alone
      prototype device uses commercially available embedded system components to
      implement a hardware platform that is capable of collecting and analyzing optical
      absorbance spectra. A mathematical model for the hemorrhagic CSF sample is then
      developed using a PLSR based regression methodology that is able to differentiate
      between SAH and blood associated with the spinal tap. This differentiations in
      achieved by quantifying bilirubin (associated with the breakdown of old blood) in
      the CSF. Initial testing on the prototype device suggests that the device is able
      to quantify bilirubin in the presence of hemoglobin over concentrations ranges
      that are clinically relevant to the patient population of interest.

PMID- 21096773
TI  - Instrumentation for the analysis of airflow limitation by the negative expiratory
      pressure technique.
AB  - The aim of this work is to describe a new instrument based on the negative
      expiratory pressure technique able to detect expiratory flow limitation (EFL) in
      patients with respiratory diseases. First, we describe the design details of a
      virtual instrument able to apply a low pressure at the mouth during tidal
      expiration, simultaneously measure flow and pressure, and automatically elaborate
      flow-volume curves. Then, the system accuracy is evaluated investigating normal
      subjects and patients with chronic obstructive pulmonary disease (COPD). These
      experimental results revealed higher (p<0.001) EFL in COPD patients (58.5+/
      19.9%) than in normal volunteers (1.5+/-2.5%). These results are in close
      agreement with the physiology, confirming the high scientific and clinical
      potential of this system.

PMID- 21096774
TI  - Instrumentation for bedside analysis of swallowing disorders.
AB  - Disordered swallowing, or dysphagia, is a common problem seen in patients
      undergoing treatment for cancer, stroke and neurodegenerative illnesses. This
      disease is associated with aspiration-induced chest infections. The methods
      currently used for diagnosis, however, are qualitative or based on expensive
      equipment. Swallowing accelerometry is a promising low-cost, quantitative and
      noninvasive tool for the evaluation of swallowing. This work describes the design
      and application of a bedside instrument able to evaluate swallowing mechanisms
      and to identify patients at risk of aspiration. Three-axis swallowing
      accelerometry was used to measure the neck vibrations associated with
      deglutition, providing analog signals to a virtual instrument developed in
      LabVIEW environment. In vivo tests in normal subjects as well as tests with
      disphagic patients showed that the system was able to easily and non-invasively
      detect changes in the swallowing acceleration pattern associated with increasing
      values of water volume (p < 0.02) and disphagia. We concluded that the developed
      system could be a useful tool for the objective bedside evaluation of patients at
      risk of aspiration.

PMID- 21096775
TI  - A contact-free respiration monitor for smart bed and ambulatory monitoring
      applications.
AB  - The development of a contact-free respiration monitor has a broad range of
      clinical applications in the home and hospital setting. Current approaches suffer
      from a variety of problems including unreliability, low sensitivity, and high
      cost. This work describes a novel approach to contact-free respiration monitoring
      that addresses these shortcomings by employing a highly sensitive capacitance
      sensor to detect variations in capacitive coupling caused by breathing. A
      prototype system consisting of a synthetic-metallic pad, sensor electronics, and
      iPhone interface was built and its performance compared experimentally to the
      gold standard technique (Respiratory Inductance Plethysmography) on both a
      healthy volunteer and SimMan robotic mannequin. The prototype sensor effectively
      captured respiratory movements over breathing rates of 5-55 bpm; achieving an
      average spectral correlation of 0.88 (CI: 0.86-0.90) and 0.95 (CI: 0.95-0.96) to
      the gold standard using the SimMan and healthy volunteer respectively.

PMID- 21096776
TI  - A portable device for the clinical assessment of upper limb motion and muscle
      synergies.
AB  - We present a device for recording and analyzing upper limb movements and muscle
      activities in a single unit. The device's outputs are related to aspects of
      clinical assessment such as joint coordination, fatigue and muscle synergies. A
      comparison with an optoelectronic motion capture system was also carried out
      during a hand to mouth and a hand to contralateral shoulder task. High
      correlation was found for the elbow angles, while analysis of the root mean
      square errors indicated that the angular outputs of the device were overestimated
      compared to the angles calculated using the optoelectronic system. Biceps and
      triceps co-contraction patterns were also observed during the hand to mouth task.
      Applications to the clinical assessment and monitoring of neurological disorders
      are discussed.

PMID- 21096777
TI  - "A window on tissue" - Using facial orientation to control endoscopic views of
      tissue depth.
AB  - An endoscope is an invaluable tool to interpret conditions within a body.
      Flexible endoscopes are controlled by a set of rotational knobs requiring a
      doctor's hands to guide and locate the view. This research uses a combination of
      a camera, facial recognition techniques and software to create a hands-free
      gesture recognition application for use by a physician to probe the internals of
      a human body. The physician will utilize the head movements to move the
      endoscopic camera freeing their hands to perform a procedure or other functions.

PMID- 21096778
TI  - Online heart rate estimation in unstable ballistocardiographic records.
AB  - When recording the pressure oscillations of a seated subject two distinct effects
      are assessed, ample vibrations due to the person's movement, and periodic
      oscillations of small amplitude due to cardiopulmonary activity, expressed by the
      ballistocardiogram (BCG). Embedding a pressure sensor in a chair's back or seat
      allows unobtrusive monitoring of the BCG. However, inconspicuously acquired
      signals are affected by numerous artifacts, often generated by the subject's
      forgetfulness, and posture changes due to lack of constrains. Moreover, the
      signal changes considerably its shape from person to person, and when the seating
      posture, or conversely, sensor position, is different. For real-time continuous
      monitoring, it is still to be found a method which, without introducing
      significant delays, can deal with such volatility. Thus, tailored calibration of
      peak detectors and other algorithms is recurrent, and even so, the neighboring
      samples of artifacts are possibly untreatable. This work evaluates the advantages
      of Empirical Mode Decomposition, as well as a coarser demodulation approach of
      the BCG signal, as dependable methods to allow real-time heart rate estimation on
      unstable BCG records. An analysis of the Fourier transform of the demodulated
      signals is the method used to provide and compare robustness of heart rate
      estimates.

PMID- 21096779
TI  - Enhancement of laplacian EEnG from humans by means of an EMD-based method.
AB  - Non-invasive recordings of intestinal myoelectrical activity (Electroenterogram,
      EEnG) are affected by very-low-frequency (VLF) interferences, respiration, ECG
      and movement artifacts. In order to identify the intestinal pacemaker activity
      (slow wave), VLF interferences and respiration should be removed from abdominal
      surface recordings. In this paper a method based on empirical mode decomposition
      is proposed to identify and cancel such interferences and to enhance external
      recordings of human EEnG. The study was carried out on 10 recording sessions in
      which it was acquired 3 surface EEnG signals by means of active laplacian
      electrodes, together with respiratory and ECG signals. The application of the
      proposed method permits to increase the signal-to-interference ratio of EEnG
      signals from - 7.9 +/- 3.3 dB to 6.1 +/- 2.7 dB. In addition, the method helps to
      identify the intestinal pacemaker activity from surface EEnG recordings: the
      dominant frequency of processed signals is 8.6 +/- 1.7 cpm which fits the
      frequency of the intestinal slow wave in the jejunum, whereas the dominant
      frequency of original signals was 1.6 +/- 1.1 cpm which is associated to VLF
      interferences.

PMID- 21096780
TI  - Application of the Empirical Mode Decomposition in the study of murmurs from
      Arteriovenous fistula stenosis.
AB  - The Empirical Mode Decomposition (EMD) is a method to decompose non linear, non
      stationary time series into a sum of different modes, named Intrinsical Mode
      Functions each one having a characteristic frequency. In the present work we used
      the EMD to investigate the properties of the recorded sounds from the
      Arteriovenous fistula on hemodialysis patients. Phonoangiographic signals coming
      from two different vessel conditions, stenotic and non-stenotic, were analyzed by
      using EMD, the mean energy and mean instantaneous frequency per IMF proved to be
      good features for classification. Three types of classification schemes were
      tested on data from the first IMf features achieving good results.

PMID- 21096781
TI  - Multiparametric detection of epileptic seizures using Empirical Mode
      Decomposition of EEG records.
AB  - Epilepsy is a neurological disorder that affects around 50 million people
      worldwide. The seizure detection is an important tool for the diagnosis of
      epilepsy. In this study, an epileptic seizure classification method based on
      features of the Empirical Mode Decomposition (EMD) of EEG records is proposed.
      The Intrinsic Mode Functions (IMFs) of EEG records are first computed, and then
      several time and frequency features of IMFs are extracted. A features selection
      based on a Mann-Whitney test and Lambda of Wilks criterion is performed, then
      these parameters are used in a linear discriminant analysis (LDA) to classify
      epileptic seizure and normal EEG segments. The algorithm was tested in 3
      intracranial channels EEG records acquired in 21 patients with refractory
      epilepsy and validated by the Epilepsy Center of the University Hospital of
      Freiburg. The signal was divided in 15 s segments. In 45517 segments analyzed
      (689 with epileptic seizures) the sensitivity and specificity obtained with this
      method were 69.4% and 69.2% respectively. It could be concluded that the
      developed method could be a promising tool for epileptic seizure detection in EEG
      records.

PMID- 21096782
TI  - The R-value of global health (conserving energy to save lives).
AB  - The world health community has been rapidly expanding immunization programs with
      the intention of reducing and eliminating the most common controllable diseases.
      Many vaccines must be kept within the strict temperature range of 2 to 8 degrees
      C. Temperature degradation and exposure to freezing temperatures will destroy the
      viability of these vaccines. The freezing problem of vaccines is often caused at
      the local level of distribution and can frequently be attributed to the methods
      and materials used to store the vaccines. PATH (Program for Applied Technology in
      Health) has issued a challenge to industry to address the problems of
      transporting and storing vaccines. In response to this challenge, SAVSU describes
      here calculated performance results for an advanced container design under
      development.

PMID- 21096783
TI  - Tips on effective presentation design and delivery.
AB  - For many of us oral presentations can be the prime means for communicating our
      ideas and our research, not only to our peers, but also to our employers and to
      potential customers. As students, you are no exception the prospect of an oral
      presentation can be daunting, the pressure is on to make a good impression with
      your research. That we are scientists presenting sometimes very complicated
      scientific ideas and results need not necessarily be a recipe for a sleep
      inducing "death by PowerPoint" presentation, rather there are simple ways in
      which we can all try and make our presentations effective and captivating. This
      session aims to give you some all-round pointers on preparing and delivering an
      effective presentation that best conveys your ideas smoothly, understandably and,
      most important, succinctly.

PMID- 21096784
TI  - An extension of the Canonical Correlation Analysis to the case of multiple
      observations of two groups of variables.
AB  - In this contribution we present a method that extends the Canonical Correlation
      Analysis for two groups of variables to the case of multiple conditions. Contrary
      to the extensions in literature based on augmenting the number of variable
      groups, the addition of conditions allows for a more robust estimate of the
      canonical correlation structure inherently present in the data. Algorithms to
      solve the estimation problem are based on joint approximate diagonalization
      algorithms for matrix sets. Simulations show the performance of the proposed
      method under two different scenarios: the calculation of a latent canonical
      structure and the estimation of a bilinear mixture model.

PMID- 21096785
TI  - Multimodal optical imaging for simultaneous in-vivo morphological and biochemical
      characterization of oral epithelial cancer.
AB  - Early detection of cancer is key to reducing morbidity and mortality.
      Morphological and chemical biomarkers presage the transition from normal to
      cancerous tissue. We have developed a noninvasive imaging system incorporating
      optical coherence tomography and fluorescence lifetime imaging to acquire both
      sets of biomarkers. Here we report early favorable results from an animal study
      designed to measure the capacity of this approach for early diagnosis of oral
      cancer.

PMID- 21096786
TI  - Skin lesion segmentation using an improved snake model.
AB  - Accurate identification of lesion borders is an important task in the analysis of
      dermoscopy images since the extraction of skin lesion borders provides important
      cues for accurate diagnosis. Snakes have been used for segmenting a variety of
      medical imagery including dermoscopy, however, due to the compromise of internal
      and external energy forces they can lead to under- or over-segmentation problems.
      In this paper, we introduce a mean shift based gradient vector flow (GVF) snake
      algorithm that drives the internal/external energies towards the correct
      direction. The proposed segmentation method incorporates a mean shift operation
      within the standard GVF cost function. Experimental results on a large set of
      diverse dermoscopy images demonstrate that the presented method accurately
      determines skin lesion borders in dermoscopy images.

PMID- 21096787
TI  - Imaging microvascular flow characteristics using laser speckle contrast imaging.
AB  - Laser speckle contrast imaging (LSCI) has classically been used to image regional
      blood flow changes in animal models. In this paper, we demonstrate the use of
      LSCI for elucidating blood flow characteristics in individual microvessels with
      diameters as small as 24um. We extracted profiles of speckle contrast values
      within individual vessels, both along their diameters and along their lengths and
      inferred that they could be attributed to the flow within the vessel. Profiles
      along the diameter of vessels revealed maxima at the center of vessels,
      consistent with fluid dynamics. These observed profiles could be fitted with
      parabolic curves with a mean coefficient of determination of 0.92. Similarly,
      analysis of speckle contrast values in the axial direction revealed profiles that
      progressively decreased in discreet quanta at branch points indicating blood flow
      bifurcations. Flow estimates obtained from speckle contrast values within
      branches of vessels obeyed the law of mass conservation with a mean error of only
      3.5%. This allowed us to elucidate the percentage distribution of blood flow into
      each of the downstream branches. This ability of LSCI to resolve blood flow
      distribution in branching microvessel trees in a minimally invasive and dye free
      environment over a wide field of view promises to find application in both the
      neuroscience laboratory as well as intraoperative neurosurgery.

PMID- 21096788
TI  - Probabilistic independent component analysis for laser speckle contrast images
      reveals in vivo multi - component vascular responses to forepaw stimulation.
AB  - Brain's functional response can be studied by observing the spatiotemporal
      dynamics of functional and structural changes in cerebral vasculature. However,
      very few studies explore detailed changes at the level of individual microvessels
      while revealing the simultaneous wide field view of microcirculation responses to
      functional stimulation. Here we use a high spatiotemporal resolution laser
      speckle contrast imaging method, in combination with probabilistic independent
      component analysis to reveal the changes of cerebral blood flow pattern in
      response to electrical forepaw stimulation in an anesthetized rat model. The
      proposed method is able to pick up the response of a single vessel down to
      approximately 20 microm diameter in a 4mm * 4mm field of view, and automatically
      extract response from multiple vascular components. Two main vascular components,
      arteriolar and capillary responses respectively, show significantly different
      temporal dynamics. Overall, the experimental results from five rats reveal that
      the specific arteriole branch proximal to the activation sites dilate prior
      consistently to the increase of blood flow in the capillaries with a latency time
      0.91 +/- 0.05s. The presented results provide novel microscopic scale evidence of
      the contribution of different vascular compartments in the hemodynamic response
      to neuronal activation.

PMID- 21096789
TI  - In vivo sarcomere imaging and fiber tension measurements.
AB  - Current work demonstrates a new method and a new device for simultaneous in vivo
      measurements of sarcomere imaging and fiber tension. Sarcomere, a building block
      of muscles, plays a critical role in muscle contraction. In the pathological
      conditions, the biomechanical properties of sarcomere and muscle fibers may be
      altered significantly. We developed a novel methodology by combining the optical
      image capture system with force measurement which allowed us to investigate the
      muscle cell properties in vivo under monitored/controlled tension. The
      methodology was validated in an in vivo rat model as well as using an in vitro
      corroboration setup. The in vivo evaluation provides us a powerful tool to
      investigate pathological changes of fibers/sarcomeres and help determine proper
      treatment.

PMID- 21096790
TI  - A novel mechanism for electrical currents inducing ventricular fibrillation: The
      three-fold way to fibrillation.
AB  - It has been long recognized that there are 2 methods for inducing VF (ventricular
      fibrillation) with electrical currents.. These are: (1) delivering a high-charge
      shock into the cardiac T-wave, and (2) delivering lower level currents for 1-5
      seconds. Present electrical safety standards are based on this understanding. We
      present new data showing a 3(rd) mechanism of inducing VF which involves the
      steps of delivering sufficient current to cause high-rate cardiac capture,
      causing cardiac output collapse, leading to ischemia, for sufficiently long
      duration, which then lowers the VFT (VF threshold) to the level of the current,
      which finally results in VF. This requires about 40% of the normal VF-induction
      current but requires a duration of minutes instead of seconds for the VF to be
      induced. Anesthetized and ventilated swine (n=6) had current delivered from a
      probe tip 10 mm from the epicardium sufficient to cause hypotensive capture but
      not directly induce VF within 5 s. After a median time of 90 s, VF was induced.
      This 3(rd) mechanism of VF induction should be studied further and considered for
      electrical safety standards and is relevant to long-duration TASER Electronic
      Control Device applications.

PMID- 21096791
TI  - Towards automated assistance for operating home medical devices.
AB  - To detect errors when subjects operate a home medical device, we observe them
      with multiple cameras. We then perform action recognition with a robust approach
      to recognize action information based on explicitly encoding motion information.
      This algorithm detects interest points and encodes not only their local
      appearance but also explicitly models local motion. Our goal is to recognize
      individual human actions in the operations of a home medical device to see if the
      patient has correctly performed the required actions in the prescribed sequence.
      Using a specific infusion pump as a test case, requiring 22 operation steps from
      6 action classes, our best classifier selects high likelihood action estimates
      from 4 available cameras, to obtain an average class recognition rate of 69%.

PMID- 21096792
TI  - Behaviour monitoring of the elderly by trajectories analysis.
AB  - This paper presents a way to keep the elderly autonomous in their daily
      activities. The principle is to monitor their behaviour and more specifically
      their trajectories of movement in the living area. Two methods have been
      developed and compared: supervised and unsupervised classification. Some results
      from data collected in a long-stay setting are shown. They highlight the
      possibility of determining normal trajectory classes, and by comparison with the
      usual situation, to trigger alarms when the trajectories are unusual.

PMID- 21096793
TI  - Automatic segmentation of triaxial accelerometry signals for falls risk
      estimation.
AB  - Falls-related injuries in the elderly population represent one of the most
      significant contributors to rising health care expense in developed countries. In
      recent years, falls detection technologies have become more common. However, very
      few have adopted a preferable falls prevention strategy through unsupervised
      monitoring in the free-living environment. The basis of the monitoring described
      herein was a self-administered directed-routine (DR) comprising three separate
      tests measured by way of a waist-mounted triaxial accelerometer. Using features
      extracted from the manually segmented signals, a reasonable estimate of falls
      risk can be achieved. We describe here a series of algorithms for automatically
      segmenting these recordings, enabling the use of the DR assessment in the
      unsupervised and home environments. The accelerometry signals, from 68 subjects
      performing the DR, were manually annotated by an observer. Using the proposed
      signal segmentation routines, an good agreement was observed between the manually
      annotated markers and the automatically estimated values. However, a decrease in
      the correlation with falls risk to 0.73 was observed using the automatic
      segmentation, compared to 0.81 when using markers manually placed by an observer.

PMID- 21096794
TI  - Diagnosing health problems from gait patterns of elderly.
AB  - A system for diagnosing health problems from gait patterns of elderly to support
      their independent living is proposed in this paper. Motion capture system, which
      consists of tags attached to the body and sensors situated in the apartment, is
      used to capture gait of elderly. Position of the tags is acquired by the sensors
      and the resulting time series of position coordinates are analyzed with machine
      learning algorithms in order to recognize the specific health problem. We propose
      novel features for training a machine learning classifier that classifies the
      user's gait into four health problems and a normal health state. Results showed
      that decision tree classifier was able to reach 95% of classification accuracy
      using 7 tags and 5 mm standard deviation of noise. Neural network outperformed it
      with classification accuracy over 99% using 8 tags with 0-20 mm noise. Control
      panel prototype has been developed to provide explanation of the automatic
      diagnosis.

PMID- 21096795
TI  - Acoustic fall detection using a circular microphone array.
AB  - Falling is a common health problem for elderly. It is reported that more than one
      third of adults 65 and older fall each year in the United States. To address the
      problem, we are currently developing an acoustic fall detection system, FADE,
      which automatically detects a fall and reports it to the caregiver. In a previous
      version, FADE used a 3-microphone linear array to eliminate the false alarms
      produced by sounds produced well above the floor level. To improve the fall
      detection in noisy and reverberant environments, we replaced the linear array by
      an 8-microphone circular array that can provide a better 3-D estimation of the
      sound location. Preliminary experiments show that the sound location estimation
      performed by the circular array is reliable and robust to interference. We
      obtained encouraging classification results on a pilot dataset with 55 falls and
      120 non-fall sounds.

PMID- 21096796
TI  - Real-time determination of skull thickness for a manually-navigated synergistic
      trepanation tool.
AB  - Trepanation of the skull is a common procedure in neurosurgery with the problems
      of dural tears and wide cutting gaps. A hand-guided instrument containing a soft
      tissue preserving saw whose cutting depth is automatically adapted on the basis
      of a-priori data (CT, MRI) is envisioned to reduce these problems.

PMID- 21096797
TI  - Evaluation of a synergistically controlled semiautomatic trepanation system for
      neurosurgery.
AB  - One of the most common procedures in neurosurgery is the trepanation of the
      skull. In this paper, a synergistically controlled handheld tool for trepanation
      is introduced. This instrument is envisioned to reduce problems of dural tears
      and wide cutting gaps by combining a soft tissue preserving saw with an automatic
      regulation of the cutting depth. Since usability and safety of the semi-automatic
      handheld device are of utmost importance, the complex interaction between the
      user and the system has been analyzed extensively. Based on prospective usability
      evaluation the user interaction design and the corresponding user-interface were
      developed. The compliance with the relevant factors effectiveness, efficiency,
      error tolerance, learnability and user satisfaction was measured in user-centered
      experiments to evaluate the usability of the semiautomatic trepanation system.
      The results confirm the user interaction design of the semiautomatic trepanation
      system and the corresponding safety strategy. The system seems to integrate
      itself smoothly into the existing workflow and keeps the surgeon aware of the
      process.

PMID- 21096798
TI  - Pilot study on verification of effectiveness on operability of assistance system
      for robotic tele-surgery using simulation.
AB  - Tele-surgery enables medical care even in remote regions, and has been
      accomplished in clinical cases by means of dedicated communication lines. To make
      tele-surgery a more widespread method of providing medical care, a surgical
      environment needs to be made available using public lines of communication, such
      as the Internet. Moreover, a support system during surgery is required, as the
      use of surgical tools is performed in an environment subject to delay. In our
      research, we focus on the operability of specific tasks conducted by surgeons
      during a medical procedure, with the aim of clarifying, by means of a simulation,
      the optimum environment for robotic tele-surgery. In the study, we set up
      experimental systems using our proposed simulation system. In addition, we
      investigate the mental workloads on subjects and verify the effect of visual
      assistance information as a pilot study. The operability of the task of gripping
      soft tissue was evaluated using a subjective workload assessment tool, the NASA
      Task Load Index. Results show that the tasks were completed, but the workload did
      not improve to less than 300ms and 400ms in the simulated environment. Verifying
      the effect of the support system was an important task under a more-than 200ms
      delay using this experiment, and future studies will evaluate the operability of
      the system under varying conditions of comfort. In addition, an intra-operative
      assistance system will be constructed using a simulation.

PMID- 21096799
TI  - First neuronavigation experiences in Uruguay.
AB  - Neuronavigation is the application of image guidance to neurosurgery where the
      position of a surgical tool can be displayed on a preoperative image. Although
      this technique has been used worldwide in the last ten years, it was never
      applied in Uruguay due to its cost. In an ongoing project, the Engineering
      Faculty (Universidad de la Republica), the Hospital de Clinicas (Medicine Faculty
      - Universidad de la Republica) and the Regional Hospital of Tacuarembo are doing
      the first experimental trials in neuronavigation. In this project, a prototype
      based on optical tracking equipment and the open source software IGSTK (Image
      Guided Surgery Toolkit) is under development and testing.

PMID- 21096800
TI  - 3D localization of ferromagnetic probes for small animal neurosurgery.
AB  - We present the design, setup and results for a magnetic navigation system for
      small animal stereotactic neurosurgery. Our system tracks the position of thin
      (diameter 0.5 mm), magnetized ferromagnetic probes inserted into brains of small
      animals, e.g. rats, for electrophysiological recordings. It is used in
      combination with the spherical assistant for stereotactic surgery (SASSU) robot
      to obtain online feedback of the probe's position. Navigation is based only on
      the static magnetic field generated by the probes thus no external excitation or
      wires are needed.

PMID- 21096801
TI  - Automated detection of fiducial screws from CT/DVT volume data for image-guided
      ENT surgery.
AB  - This paper presents an automated solution for precise detection of fiducial
      screws from three-dimensional (3D) Computerized Tomography (CT)/Digital Volume
      Tomography (DVT) data for image-guided ENT surgery. Unlike previously published
      solutions, we regard the detection of the fiducial screws from the CT/DVT volume
      data as a pose estimation problem. We thus developed a model-based solution.
      Starting from a user-supplied initialization, our solution detects the fiducial
      screws by iteratively matching a computer aided design (CAD) model of the
      fiducial screw to features extracted from the CT/DVT data. We validated our
      solution on one conventional CT dataset and on five DVT volume datasets,
      resulting in a total detection of 24 fiducial screws. Our experimental results
      indicate that the proposed solution achieves much higher reproducibility and
      precision than the manual detection. Further comparison shows that the proposed
      solution produces better results on the DVT dataset than on the conventional CT
      dataset.

PMID- 21096802
TI  - Automatic detector of high frequency oscillations for human recordings with
      macroelectrodes.
AB  - High Frequency Oscillations (HFOs) in the EEG are a promising biomarker of
      epileptogenic tissue. Given that the visual marking of HFOs is highly time
      consuming and subjective, automatic detectors are necessary. In this study, we
      present a novel automatic detector that detects HFOs by incorporating information
      of previously detected baselines. The detector was trained on 72 channels and
      tested on 278, achieving a mean sensitivity of 96.8% with a mean false positive
      rate of 4.86%. This low rate is reasonable since only visually marked baseline
      segments were considered as the true negatives. This detector could be useful for
      the systematic study of HFOs and for their eventual clinical application.

PMID- 21096803
TI  - An automatic multi-lead electrocardiogram segmentation algorithm based on abrupt
      change detection.
AB  - Automatic detection of electrocardiogram (ECG) waves provides important
      information for cardiac disease diagnosis. In this paper a new algorithm is
      proposed for automatic ECG segmentation based on multi-lead ECG processing. Two
      auxiliary signals are computed from the first and second derivatives of several
      ECG leads signals. One auxiliary signal is used for R peak detection and the
      other for ECG waves delimitation. A statistical hypothesis testing is finally
      applied to one of the auxiliary signals in order to detect abrupt mean changes.
      Preliminary experimental results show that the detected mean changes instants
      coincide with the boundaries of the ECG waves.

PMID- 21096804
TI  - Destructive power dynamics of alpha-theta oscillations via spike and wave in CA3.
AB  - The power dynamics of alpha-theta oscillations via inter-ictal spikes and waves
      (SWs) in CA3 is investigated by means of Hilbert transform and the statistical
      method based on CA3 channel of LFP(Local Field Potention) data sampled on total 6
      rats in resting with sniffing and of iEEG data on total 10 patients in quiet
      wakefulness. The comparison of alpha-theta power is done between the inter-ictal
      groups and control groups. It is concluded that the inter-ictal SWs can disrupt
      the power of alpha-theta oscillations, leading to the decreased power after SW.
      Because the alpha-theta oscillations are related with the cognition, it is
      estimated that the inter-ictal SWs can negatively affecte the cognitive function
      during the inter-ictal dynamics, although the alpha-theta power will be
      recoverable in some days after injections, even exceed over the power level
      before injections.

PMID- 21096805
TI  - Nonlinearity of EHG signals used to distinguish active labor from normal
      pregnancy contractions.
AB  - Labor prediction using the electrohysterogram has immediate clinical applications
      and has been the aim of several studies in recent years. Studies using various
      linear methods such as classic spectral analysis do not give clinically useful
      results. In this paper we present the use of two methods that investigate
      nonlinearity to predict normal labor. We show the comparison between a linear
      method that is known from the literature (mean power frequency) and two nonlinear
      methods (approximate entropy and time reversibility) using ROC analysis. The
      comparison indicates that the best method for pretreatment to classify pregnancy
      and labor signals is time reversibility. The results indicate that time
      reversibility is a very promising tool for distinguishing between labor and
      physiological contractions during pregnancy. This could be the first step in
      developing a clinical application method to predict preterm labor.

PMID- 21096806
TI  - A state space based approach in non-linear hemodynamic response modeling with
      fMRI data.
AB  - In this paper we use the modified and integrated version of the balloon model in
      the analysis of fMRI data. We propose a new state space model realization for
      this balloon model and represent it with the standard A,B,C and D matrices widely
      used in system theory. A second order Pade approximation with equal numerator and
      denominator degree is used for the time delay approximation in the modeling of
      the cerebral blood flow. The results obtained through numerical solutions showed
      that the new state space model realization is in close agreement to the actual
      modified and integrated version of the balloon model. This new system theoretic
      formulation is likely to open doors to a novel way of analyzing fMRI data with
      real time robust estimators. With further development and validation, the new
      model has the potential to devise a generalized measure to make a significant
      contribution to improve the diagnosis and treatment of clinical scenarios where
      the brain functioning get altered. Concepts from system theory can readily be
      used in the analysis of fMRI data and the subsequent synthesis of filters and
      estimators.

PMID- 21096807
TI  - Segmentation of airways in lungs using projections in 3-D CT angiography images.
AB  - In diagnosing lung diseases, the structure and shape of airways in lungs are of
      great importance. In this paper we propose a novel method for segmenting low
      contrast 3-D CTA images of airways in lungs. Our approach is an edge-detecting
      slice-by-slice segmentation method, capable of segmenting low contrasted airway
      regions. Our segmentation using projections method shows robustness in images
      with high presence of noise.

PMID- 21096808
TI  - Classification of clusters of microcalcifications in digital breast
      tomosynthesis.
AB  - The detection of microcalcifications, reconstruction of clusters of
      microcalcifications and their subsequent classification into malignant and benign
      are important tasks in the early detection of breast cancer. Digital breast
      tomosynthesis (DBT) provides new opportunities in such tasks. By utilizing the
      multiple projections in DBT and using the geometry of DBT, we have developed an
      approach to them based on epipolar curves. It improves the sensitivity and
      specificity in detection; provides information for estimation of 3D positions of
      microcalcifications; and facilitates classification. We have generated 15
      simulated datasets, each with a microcalcification cluster based on an
      ellipsoidal shape. We estimate the 3D positions of the microcalcifications in
      each of the clusters and reconstruct the clusters as ellipsoids. We classify each
      cluster as malignant or benign based on the parameters of the ellipsoids. The
      classification result is compared with the ground truth. Our results show that
      the deviations between the actual and estimated 3D positions of the
      microcalcification, and the actual and estimated parameters of the ellipsoids are
      sufficiently small that the classification results are 100% correct. This
      demonstrates the feasibility in cluster classification in 3D.

PMID- 21096809
TI  - Insertion experiments of a biologically inspired microtextured and multi-part
      probe based on reciprocal motion.
AB  - While there have been significant advances in minimally invasive surgical
      instrumentation, the majority of tools still rely on a push from the back to aid
      insertion into the tissue, whether the process is manual or servo assisted. In
      this work, a novel approach to tool insertion is proposed which is based on the
      concept of a multi-part probe with at least three interlocking segments. By means
      of a sequential insertion process, where each segment is pushed further into the
      tissue while stabilized by the remaining stationary parts, the multi-part probe
      concept is shown to successfully "insinuate itself" within a synthetic soft
      tissue specimen without the need for an overall forward push. The presence of an
      anisotropic microtextured outer probe surface is also shown to affect the overall
      speed of insertion and can thus be used to optimize the interaction forces at the
      probe-tissue interface. A measured reduction in the force transferred to the back
      of the specimen also suggests that this approach to tool insertion may result in
      reduced tissue disruption, a result which could lead to less tissue damage and a
      reduction in target displacement.

PMID- 21096810
TI  - Incremental learning control of the DLR-HIT-Hand II during interaction tasks.
AB  - In this paper a bio-inspired control architecture for a robotic hand is
      presented. It relies on the same mechanisms of learning inverse internal models
      studied in humans. The control is capable of developing an internal
      representation of the hand interacting with the environment and updating it by
      means of the interaction forces that arise during contact. The learning paradigm
      exploits LWPR networks, which allow efficient incremental online learning through
      the use of spatially localized linear regression models. Additionally this
      paradigm limits negative interference when learning multiple tasks. The
      architecture is validated on a simulated finger of the DLR-HIT-Hand II performing
      closing movements in presence of two different viscous force fields, perturbing
      its motion.

PMID- 21096811
TI  - Detailed finite element simulations of probe insertion into solid elastic
      material using a cohesive zone approach.
AB  - In this paper a method is presented for detailed finite element modelling of
      probe insertion into an elastic material. This is part of an ongoing
      investigation into the mechanics of a novel, biomimetic, soft-tissue probe
      currently under development at Imperial College, London. Analysis is performed
      using a 'cohesive zone' approach by integrating multiple cohesive elements into a
      finite element mesh using Abaqus software. Cohesive zones with variable crack
      paths, generated by both remote tensile and contact loading, and substantial
      probe penetration along an arbitrarily curved crack path are demonstrated. These
      advances are critical to understanding probe interactions for the development of
      an existing prototype and control strategy.

PMID- 21096812
TI  - Development and validation of a numerical model for cross-section optimization of
      a multi-part probe for soft tissue intervention.
AB  - The popularity of minimally invasive surgical procedures is driving the
      development of novel, safer and more accurate surgical tools. In this context a
      multi-part probe for soft tissue surgery is being developed in the Mechatronics
      in Medicine Laboratory at Imperial College, London. This study reports an
      optimization procedure using finite element methods, for the identification of an
      interlock geometry able to limit the separation of the segments composing the
      multi-part probe. An optimal geometry was obtained and the corresponding three
      dimensional finite element model validated experimentally. Simulation results are
      shown to be consistent with the physical experiments. The outcome of this study
      is an important step in the provision of a novel miniature steerable probe for
      surgery.

PMID- 21096813
TI  - Anticipatory visual perception as a bio-inspired mechanism underlying robot
      locomotion.
AB  - Anticipation of sensory consequences of actions is critical for the predictive
      control of movement that explains most of our sensory-motor behaviors. Plenty of
      neuroscientific studies in humans suggest evidence of anticipatory mechanisms
      based on internal models. Several robotic implementations of predictive behaviors
      have been inspired on those biological mechanisms in order to achieve adaptive
      agents. This paper provides an overview of such neuroscientific and robotic
      evidences; a high-level architecture of sensory-motor coordination based on
      anticipatory visual perception and internal models is then introduced; and
      finally, the paper concludes by discussing the relevance of the proposed
      architecture within the context of current research in humanoid robotics.

PMID- 21096814
TI  - A portable device to represent different views to both eyes.
AB  - To investigate the flexible adaptation of human visual system, we developed a
      system to provide different view fields to both eyes of a user respectively. The
      system named "Virtual Chameleon" consists of two CCD cameras independently
      controlled and a head-mounted display was used by twelve healthy volunteers.
      Eleven of them became able to independently control visual axes and understood
      two different views. The successful users of the system were able to actively
      control visual axes by manipulating 3D sensors held by their both hands, to watch
      independent view fields presented to the left and right eyes, and to look around
      as chameleons do. The results raise interesting question on adaption to provided
      two independent view fields.

PMID- 21096815
TI  - Analytical validation of COMSOL Multiphysics for theoretical models of
      Radiofrequency ablation including the Hyperbolic Bioheat transfer equation.
AB  - In this paper we outline our main findings about the differences between the use
      of the Bioheat Equation and the Hyperbolic Bioheat Equation in theoretical models
      for Radiofrequency (RF) ablation. At the moment, we have been working on the
      analytical approach to solve both equations, but more recently, we have
      considered numerical models based on the Finite Element Method (FEM). As a first
      step to use FEM, we conducted a comparative study between the temperature
      profiles obtained from the analytical solutions and those obtained from FEM.
      Regarding the differences between both methods, we obtain agreement in less than
      5% of relative differences. Then FEM is a good alternative to model heating of
      biological tissues using BE and HBE in, for example, more complex and realistic
      geometries.

PMID- 21096816
TI  - Simulations of transport regime in electrodeposition in different viscosity
      scenarios.
AB  - In this work we study the effects of viscosity variations in thin-layer
      electrochemical deposition (ECD) under galvanostatic conditions through
      experimental measurements and theoretical modeling. The theoretical model,
      written in terms of dimensionless quantities, describes diffusive, migratory and
      convective ion transport in a fluid under galvanostatic conditions. Experiments
      reveal that as viscosity increases, convection decreases when the cell resistance
      remains constant. Our numerical model predicts that as viscosity increases,
      electroconvection becomes less relevant and concentration and convective fronts
      slow down. The time scaling of this phenomenon is studied and compared to
      previously reported low viscosity solution studies.

PMID- 21096817
TI  - Sex and age related differences in drug induced QT prolongation by dofetilide
      under reduced repolarization reserve in simulated ventricular cells.
AB  - The aim of this study was to investigate sex and age related differences in drug
      induced QT prolongation by dofetilide under reduced repolarization reserve in
      simulated ventricular cells. Left ventricular endocardial action potentials were
      simulated using a modified Luo Rudy model. Sex, age and regional differences in
      currents I(CaL), IK(r), IK(s), and I(to) were incorporated into the model by
      modifying the equations representing them. A model of dofetilide, a class III
      antiarrhythmic drug, was developed and included into a ventricular cell models.
      The reduced repolarization reserve was reproduced decreasing the IKs current. Our
      results shown that the adult female cells had longer action potentials, a steeper
      APD-BCL relationship and a higher susceptibility to EADs than adult male cells,
      under control, drug induced and reduced repolarization reserve conditions. On the
      other hand, young female and young male cells had similar action potentials under
      control conditions. However, young male cells had longer action potentials and
      higher susceptibility to EADs than young female cells under drug induced and
      reduced repolarization reserve conditions. Sex and age dependent differences in
      I(CaL), IKr, IKs, and Ito may explain the age and sex disparities in prolongation
      of APD by the action of dofetilide.

PMID- 21096818
TI  - GPU accelerated FDTD solver and its application in MRI.
AB  - The finite difference time domain (FDTD) method is a popular technique for
      computational electromagnetics (CEM). The large computational power often
      required, however, has been a limiting factor for its applications. In this
      paper, we will present a graphics processing unit (GPU)-based parallel FDTD
      solver and its successful application to the investigation of a novel B1 shimming
      scheme for high-field magnetic resonance imaging (MRI). The optimized shimming
      scheme exhibits considerably improved transmit B(1) profiles. The GPU
      implementation dramatically shortened the runtime of FDTD simulation of
      electromagnetic field compared with its CPU counterpart. The acceleration in
      runtime has made such investigation possible, and will pave the way for other
      studies of large-scale computational electromagnetic problems in modern MRI which
      were previously impractical.

PMID- 21096819
TI  - Phase unwrapping using region-based markov random field model.
AB  - Phase unwrapping is a classical problem in Magnetic Resonance Imaging (MRI),
      Interferometric Synthetic Aperture Radar and Sonar (InSAR/InSAS), fringe pattern
      analysis, and spectroscopy. Although many methods have been proposed to address
      this problem, robust and effective phase unwrapping remains a challenge. This
      paper presents a novel phase unwrapping method using a region-based Markov Random
      Field (MRF) model. Specifically, the phase image is segmented into regions within
      which the phase is not wrapped. Then, the phase image is unwrapped between
      different regions using an improved Highest Confidence First (HCF) algorithm to
      optimize the MRF model. The proposed method has desirable theoretical properties
      as well as an efficient implementation. Simulations and experimental results on
      MRI images show that the proposed method provides similar or improved phase
      unwrapping than Phase Unwrapping MAx-flow/min-cut (PUMA) method and ZpM method.

PMID- 21096820
TI  - Coil reduction in parallel excitation with large array.
AB  - Parallel excitation using coil array has been introduced in MRI as an effective
      method to design multi-dimensional spatially selective RF pulses. Generally, all
      transmit coil elements are used simultaneously in parallel excitation. In case of
      large array, RF pulse design requires significant computation time and memory
      size. In this paper, a method using reduced number of coils for parallel
      excitation is proposed to take advantage of localized coil transmit sensitivity
      in large array. Specifically, a subset of coils in the large array can be
      selected based on coil sensitivity coverage and desired excitation pattern.
      Simulation results with both spiral and EPI k-space trajectories show that
      proposed method is effective in achieving high excitation resolution at different
      acceleration factors while the computation time and memory requirement are
      greatly reduced.

PMID- 21096821
TI  - DWI acquisition schemes and diffusion tensor estimation: a simulation-based
      study.
AB  - Diffusion Tensor Imaging (DTI) is the most used paradigm among the Diffusion
      Weighted Magnetic Resonance Imaging techniques, due to its inner simplicity and
      huge application potential. Least Squares has become the standard technique to
      estimate the Diffusion Tensor (DT) from Diffusion Weighted Images. This approach
      is known to be optimal when the acquired data follows Gaussian, Rician or non
      central chi distributions. In this paper we study the effect of different
      acquisition schemes over the quality of the DT estimation. The following cases
      are considered: single coil, multiple coil fully sampled, and accelerated
      subsampled multiple coil acquisitions with SENSE and GRAPPA reconstructions.
      Reconstructed subsampled data will show an acceleration in the acquisition
      process, but also greater variance and bias in the DT estimation.

PMID- 21096822
TI  - High-performance 3D compressive sensing MRI reconstruction.
AB  - Compressive Sensing (CS) is a nascent sampling and reconstruction paradigm that
      describes how sparse or compressible signals can be accurately approximated using
      many fewer samples than traditionally believed. In magnetic resonance imaging
      (MRI), where scan duration is directly proportional to the number of acquired
      samples, CS has the potential to dramatically decrease scan time. However, the
      computationally expensive nature of CS reconstructions has so far precluded their
      use in routine clinical practice - instead, more-easily generated but lower
      quality images continue to be used. We investigate the development and
      optimization of a proven inexact quasi-Newton CS reconstruction algorithm on
      several modern parallel architectures, including CPUs, GPUs, and Intel's Many
      Integrated Core (MIC) architecture. Our (optimized) baseline implementation on a
      quad-core Core i7 is able to reconstruct a 256 * 160*80 volume of the
      neurovasculature from an 8-channel, 10 * undersampled data set within 56 seconds,
      which is already a significant improvement over existing implementations. The
      latest six-core Core i7 reduces the reconstruction time further to 32 seconds.
      Moreover, we show that the CS algorithm benefits from modern throughput-oriented
      architectures. Specifically, our CUDA-base implementation on NVIDIA GTX480
      reconstructs the same dataset in 16 seconds, while Intel's Knights Ferry (KNF) of
      the MIC architecture even reduces the time to 12 seconds. Such level of
      performance allows the neurovascular dataset to be reconstructed within a
      clinically viable time.

PMID- 21096823
TI  - Role of substrate microstructure on osteogenic differentiation of mesenchymal
      stem cells.
AB  - The objective of this work was to investigate the effect of substrate
      microstructure (planar versus microtubular geometry) on the extent of osteogenic
      differentiation of bone mesenchymal stem (BMS) cells. For laminated sheets, the
      BMS cell suspension was seeded on the sheets and cultured in complete osteogenic
      media. For laminated microtubes, the BMS cell suspension was injected in the
      tubes and allowed to incubate in osteogenic media. BMS cells cultured in osteon
      mimetic microtubes had drastically higher ALPase activity and calcium content,
      compared to laminated sheets. The data demonstrate that the 3D environment of the
      microtubes profoundly affects osteogenic differentiation of the BMS cells,
      compared to the 2D laminated sheets.

PMID- 21096824
TI  - Fabrication and characterization of tough elastomeric fibrous scaffolds for
      tissue engineering applications.
AB  - Development of biodegradable tough elastomeric scaffolds are important for
      engineering tissues such as myocardium and heart valves that experience dynamic
      environments in vivo. Biomaterial scaffolds should ideally provide appropriate
      physical, chemical and mechanical cues to the seeded cells to closely mimic the
      native ECM. Collagen fibers form an important component of native myocardium as
      well as heart valve leaflets and provide necessary tensile properties to these
      tissues. Amongst various polymers, collagen mimicking biodegradable elastomer,
      Poly-(glycerol-sebacate) (PGS) has shown great promise in microfabricated
      scaffolds for cardiac tissue engineering. However, its use is limited by its
      solubility and the ability to cast nano-/microfibrous structures. For its
      superior mechanical properties, thermal or UV crosslinking of the pre-polymer is
      required under high temperatures and vacuum limiting fabrication of fibers. In
      this work, we fabricated electrospun PGS fibers were fabricated by simply
      blending it with biodegradable polycaprolactone (PCL) polymer without any post
      processing. It was hypothesized that microfibrous PGS-PCL scaffolds would provide
      appropriate physical (fibrous structure) and chemical (balanced hydrophilicity
      and hydrophobicity) to the cells in addition to the mechanical properties.

PMID- 21096826
TI  - Physiological significance of pressure-volume relationship: a load-independent
      index and a determinant of pump function.
AB  - Pressure-volume relationship permits conceptual integration with time-varying
      elastance, stress-strain relationship, and pressure-volume area. It has also
      superior usefulness to other indexes, both as a load-independent index of
      ventricular contractility and as a determinant of ventricular pump function.

PMID- 21096825
TI  - Implantable hemodynamic monitors: Can be conductance catheter system successfully
      implemented?
AB  - Successful management of cardiac heart failure requires a multifactorial
      approaching. It has been suggested that implantable hemodynamic long-term
      monitoring can improve patient care. This paper presents an analysis of the
      hemodynamic parameters commonly recorded, the most used implantable devices and
      their associated clinical trials. Newly implantable miniaturized sensors and
      devices are revisited. Finally, a newly implantable conductance-catheter based
      system is presented. The feasibility to realise volume and pressure measurements
      in the human left ventricular cavity using an implantable conductance-catheter
      based system is evaluated. It has the advantage to obtain LV signals
      continuously. In addition, it allows to realise maneuvers such as calibration and
      LV function by telemetry being avoiding patient hospitalizations. The rapid
      advances in device monitoring capabilities could change the new paradigm of the
      heart disease management.

PMID- 21096827
TI  - The pressure-volume relationship of the heart: past, present and future.
AB  - The pressure-volume relationship of the heart was first reported more than a
      century ago. It was not widely accepted, however, until the mid-1970s. The
      pressure-volume diagram became a central theme of cardiac mechanics once it was
      shown to be a good representation of ventricular mechanics. Early in 1980s, the
      introduction of the ventricular interaction with afterload using effective
      arterial elastance made it possible to translate ventricular mechanical
      properties represented by the pressure-volume relationship to the pumping ability
      of the heart. Furthermore incorporating the framework of ventricular arterial
      interaction into the classic Guyton's circulatory equilibrium early in 2000s
      enabled us to express quantitatively how mechanical properties of the ventricles
      and vascular systems determine the circulatory equilibrium. Successful
      quantitative descriptions of circulatory equilibrium using the pressure-volume
      concept would promote basic cardiovascular physiology and accelerate its clinical
      applications.

PMID- 21096828
TI  - Psychophysiological signals associated with affective states.
AB  - We present a preliminary quantitative study aimed at developing an optimal
      standard protocol for automatic classification of specific affective states as
      related to human- computer interactions. This goal is mainly achieved by
      comparing standard psychological test-reports to quantitative measures derived
      from simultaneous non-invasive acquisition of psychophysiological signals of
      interest, namely respiration, galvanic skin response, blood volume pulse,
      electrocardiogram and electroencephalogram. Forty-three healthy students were
      exposed to computer-mediated stimuli, while wearable non-invasive sensors were
      applied in order to collect the physiological data. The stimuli were designed to
      elicit three distinct affective states: relaxation, engagement and stress. In
      this work we report how our quantitative analysis has helped in redefining
      important aspects of the protocol, and we show preliminary findings related to
      the specific psychophysiological patterns correlating with the three target
      affective states. Results further suggest that some of the quantitative measures
      might be useful in characterizing specific affective states.

PMID- 21096829
TI  - A differential autoregressive modeling approach within a point process framework
      for non-stationary heartbeat intervals analysis.
AB  - Modeling heartbeat variability remains a challenging signal-processing goal in
      the presence of highly non-stationary cardiovascular control dynamics. We propose
      a novel differential autoregressive modeling approach within a point process
      probability framework for analyzing R-R interval and blood pressure variations.
      We apply the proposed model to both synthetic and experimental heartbeat
      intervals observed in time-varying conditions. The model is found to be extremely
      effective in tracking non-stationary heartbeat dynamics, as evidenced by the
      excellent goodness-of-fit performance. Results further demonstrate the ability of
      the method to appropriately quantify the non-stationary evolution of baroreflex
      sensitivity in changing physiological and pharmacological conditions.

PMID- 21096830
TI  - Assessing the severity and improving the understanding of sleep-related breathing
      disorders in heart failure patients.
AB  - In this manuscript we present an overview of novel signal processing techniques
      developed by our group to reduce scoring time in the assessment of the severity
      of sleep-related breathing disorders in heart failure patients and to detect
      sleep/wake fluctuations during periodic breathing. Besides describing these
      methods, we present the results of validation experiments. Our work shows that
      novel signal processing techniques can reduce costs and resources needed to
      screen the patients and can provide relevant information for better understanding
      the role of wake/sleep transitions in the development and maintenance of
      breathing disorders.

PMID- 21096831
TI  - Respiration effect on single and multi lead ECG delineation strategies.
AB  - The main purpose of this work is to study the influence of the mechanical effect
      of the respiration over T wave end delineation. The performance of automatic
      delineation systems based in Wavelet Transform (WT) was compared, considering
      single lead (SL), post processing selection rules (SLR) and multi lead (ML)
      approaches. The T wave locations obtained over real and simulated ECG signals
      were analyzed together with the respective respiratory signal (ECG-derived or
      simulated). The linear relation between the variations on obtained marks and the
      mechanical effect of the respiration was measured using spectral coherence. With
      respect to the ML strategy we also explored the evolution of the
      vectorcardiographic spatial loop using the direction of maximum projection of the
      WT in the region close to the T wave end (T(e)). The relation between this
      direction and the respiration is also explored. The marks obtained from the SLR
      and ML delineation strategies show advantage over the SL strategy based marks.
      The coherence around the respiratory frequency between the respiratory signal and
      the error in T end marks was found to be higher using SLR (a minimum of 0.92)
      than using ML (a maximum of 0.80). According to obtained results, the multi lead
      delineation presents a lower sensibility to the mechanical effect of the
      respiration for the T wave end delineation, particularly the obtained with ML.

PMID- 21096832
TI  - Time-varying spectral analysis for comparison of HRV and PPG variability during
      tilt table test.
AB  - In this work we assessed the possibility of using the pulse rate variability
      (PRV) extracted from photoplethysmography signal as an alternative measurement of
      the HRV signal in non-stationary conditions. The study is based on the analysis
      of the changes observed during tilt table test in the heart rate modulation of 17
      young subjects. Time-varying spectral properties of both signals were compared by
      time-frequency (TF) and TF coherence analysis. In addition, the effect of
      replacing PRV with HRV in the assessment of the changes of the autonomic
      modulation of the heart rate was considered. Time-frequency analysis revealed
      that: the TF spectra of both signals were highly correlated (0.99 +/- 0.01); the
      difference between the instantaneous power, in LF and HF bands, obtained from HRV
      and PRV was small (, 10(-3) s(-2)) and their temporal patterns were highly
      correlated (0.98 +/- 0.04 and 0.95 +/- 0.06 in LF and HF bands respectively); TF
      coherence in LF and HF bands was high (0.97 +/- 0.04 and 0.89 +/- 0.08,
      respectively). Finally, the instantaneous power in LF band was observed to
      significantly increase during head-up tilt by both HRV and PRV analysis. These
      results suggest that, although some small differences in the time-varying
      spectral indices extracted from HRV and PRV exist, mainly in the HF band
      associated with respiration, PRV could be used as an acceptable surrogate of HRV
      during non-stationary conditions, at least during tilt table test.

PMID- 21096833
TI  - Non invasive vascular evaluation and subclinical atherosclerosis: a new
      perspective to evaluate cardiovascular risk.
AB  - Techniques as Intima Media Thickness (IMT) and (Pulse Wave velocity) PWV have
      been strongly suggested by European and American Guidelines to assess subclinical
      ahterosclerotic vascular disease as target organ damage, and when they are
      present, they have been clearly associated to an increased risk of cardiovascular
      complications and death.

PMID- 21096834
TI  - Arterial evaluation in type 2 diabetes mellitus.
AB  - Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a
      new pandemia. Cardiovascular disease is the major cause of morbidity and
      mortality in type 2 DM, due to arterial structure and function changes.
      Assessment of arterial structure and biomechanics, by non-invasive methods and
      parameters, can be used to detect early alterations related to DM.

PMID- 21096835
TI  - Response of human coronary arteries at different mechanical conditions.
AB  - The lack of reliable mechanical data on coronary arteries hampers the application
      of numerical models to vascular problems, and precludes physicians from knowing
      in advance the response of coronary arteries to the different interventions. In
      this work, the mechanical properties of human coronary arteries have been
      characterized. Whole samples from human right (RC) and left anterior descending
      (LAD) coronary arteries aged between 23 and 83 years have been studied by means
      of in-vitro tensile testing up to failure. Knowledge of the mechanical response
      of human coronary arteries could be applied to optimize the election of vascular
      grafts or to prevent arterial damage during angioplasty.

PMID- 21096836
TI  - The evolution of tissue engineered vascular grafts: from research to clinical
      practice.
AB  - There is a considerable need for alternatives to the autologous vein and artery
      tissues used for vascular reconstructive surgeries such as CABG, lower limb
      bypass, arteriovenous shunts and repair of congenital defects of the pulmonary
      outflow tract. So far, synthetic materials have not matched the efficacy of
      native tissues, particularly small diameter applications. We have developed a
      completely autologous approach called sheet based tissue engineering.

PMID- 21096837
TI  - Post-implant evaluation of the anastomotic biomechanical coupling between human
      native arteries and arterial cryografts implanted in lower-limb revascularization
      procedures.
AB  - In the past, the reduced availability and problems with the preservation/storage
      limited the use of cryopreserved /defrosted arteries (cryografts) in lower limb
      revascularization procedures. However, the recent development of cryopreservation
      techniques enhanced cryografts availability and value, and renewed the interest
      in their use as vascular substitutes. Anyway, some issues related with the
      cryografts properties and with their usefulness remain to be clarified.

PMID- 21096838
TI  - High-density EMG E-textile systems for the control of active prostheses.
AB  - Myoelectric control of active prostheses requires electrode systems that are easy
      to apply for daily repositioning of the electrodes by the user. In this study we
      propose the use of Smart Fabric and Interactive Textile (SFIT) systems as an
      alternative solution for recording high-density EMG signals for myoelectric
      control. A sleeve covering the upper and lower arm, which contains 100 electrodes
      arranged in four grids of 5 * 5 electrodes, was used to record EMG signals in 3
      subjects during the execution of 9 tasks of the wrist and hand. The signals were
      analyzed by extracting wavelet coefficients which were classified with linear
      discriminant analysis. The average classification accuracy for the nine tasks was
      89.1 +/- 1.9 %. These results show that SFIT systems can be used as an effective
      way for muscle-machine interfacing.

PMID- 21096839
TI  - Fire fighters and rescuers monitoring through wearable sensors: The ProeTEX
      project.
AB  - The final generation of ProeTEX prototypes has been delivered in April 2010: it
      is based on two sets of sensorized garments devoted to monitor the health status
      of emergency operators working in harsh environments. This new release of
      garments shows several improvements with respect to the previous ones, and it is
      characterized by a major specialization to the requirements imposed by the
      different categories of end-users (Fire-Fighters, Civil Protection rescuers)
      addressed by the project. Each ProeTEX prototype is provided with a communication
      infrastructure allowing the real-time remote transmission of data recorded by the
      wearable sensors, and the presentation of such data to possible managers
      supervising the activities of the first line responders. After the delivery of
      the prototypes, an intense validation of the garments is being carried out both
      in laboratories, specialized in physiological measures, and in simulated fire
      fighting scenarios. In such a context, this paper presents the main features
      characterizing the final ProeTEX prototypes and preliminary results of their
      laboratory assessment.

PMID- 21096840
TI  - Towards a smart glove: arousal recognition based on textile Electrodermal
      Response.
AB  - This paper investigates the possibility of using Electrodermal Response, acquired
      by a sensing fabric glove with embedded textile electrodes, as reliable means for
      emotion recognition. Here, all the essential steps for an automatic recognition
      system are described, from the recording of physiological data set to a feature
      based multiclass classification. Data were collected from 35 healthy volunteers
      during arousal elicitation by means of International Affective Picture System
      (IAPS) pictures. Experimental results show high discrimination after twenty steps
      of cross validation.

PMID- 21096841
TI  - PSYCHE: personalised monitoring systems for care in mental health.
AB  - One of the areas of great demand for the need of continuous monitoring, patient
      participation and medical prediction is that of mood disorders, more specifically
      bipolar disorders. Due to the unpredictable and episodic nature of bipolar
      disorder, it is necessary to take the traditional standard procedures of mood
      assessment through the administration of rating scales and questionnaires and
      integrate this with tangible data found in emerging research on central and
      peripheral changes in brain function that may be associated to the clinical
      status and response to treatment throughout the course of bipolar disorder. This
      paper presents PSYCHE system, a personal, cost-effective, multi-parametric
      monitoring system based on textile platforms and portable sensing devices for the
      long term and short term acquisition of data from selected class of patients
      affected by mood disorders. The acquired data will be processed and analyzed in
      the established platform that takes into account the Electronic Health Records
      (EHR) of the patient, a personalized data referee system, as well as medical
      analysis in order to verify the diagnosis and help in prognosis of the illness.
      Constant feedback and monitoring will be used to manage the illness, to give
      patients support, to facilitate interaction between patient and physician as well
      as to alert professionals in case of patients relapse and depressive or manic
      episodes income, as the ultimate goal is to identify signal trends indicating
      detection and prediction of critical events.

PMID- 21096842
TI  - Automatic detection of sleep macrostructure based on a sensorized T-shirt.
AB  - In the present work we apply a fully automatic procedure to the analysis of
      signal coming from a sensorized T-shit, worn during the night, for sleep
      evaluation. The goodness and reliability of the signals recorded trough the T
      shirt was previously tested, while the employed algorithms for feature extraction
      and sleep classification were previously developed on standard ECG recordings and
      the obtained classification was compared to the standard clinical practice based
      on polysomnography (PSG). In the present work we combined T-shirt recordings and
      automatic classification and could obtain reliable sleep profiles, i.e. the sleep
      classification in WAKE, REM (rapid eye movement) and NREM stages, based on heart
      rate variability (HRV), respiration and movement signals.

PMID- 21096843
TI  - Improved disparity based image processing in 3D CT subtractive angiography.
AB  - The paper describes a set of approaches and routines designed to improve results
      in CT based 3D subtractive angiography of lower extremities via better global
      locally defined image data registration. Starting from the generic concept of 3D
      disparity-based flexible registration, modifications of this idea are made
      founded on prior anatomical knowledge, as segmentation into individual bone
      areas, their rigid registration followed by constrained flexible registration,
      and flexible registration of soft tissue volumes. After final subtraction, fusion
      of the individually derived volumes into the full volume of extremities provides
      the medically assessable results. The level of detail in minor vessels, and
      continuity of vessels including those in direct contact with the bones, have been
      found much better clinically than those achieved by standard contemporary
      commercial software.

PMID- 21096844
TI  - ECG gated tomographic reconstruction for 3-D rotational coronary angiography.
AB  - A method is proposed for 3-D reconstruction of coronary from a limited number of
      projections in rotational angiography. A Bayesian maximum a posteriori (MAP)
      estimation is applied with a Poisson distributed projection to reconstruct the 3D
      coronary tree at a given instant of the cardiac cycle. Several regularizers are
      investigated L0-norm, L1 and L2 -norm in order to take into account the sparsity
      of the data. Evaluations are reported on simulated data obtained from a 3D
      dynamic sequence acquired on a 64-slice GE LightSpeed CT scan. A performance
      study is conducted to evaluate the quality of the reconstruction of the
      structures.

PMID- 21096845
TI  - Modeling of the lung nodules for detection in LDCT scans.
AB  - A novel approach is proposed for generating data driven models of the lung
      nodules appearing in low dose CT (LDCT) scans of the human chest. Four types of
      common lung nodules are analyzed using Active Appearance Model methods to create
      descriptive lung nodule models. The proposed approach is also applicable for
      automatic classification of nodules into pathologies given a descriptive
      database. This approach is a major step forward for early diagnosis of lung
      cancer. We show the performance of the new nodule models on clinical datasets
      which illustrates significant improvements in both sensitivity and specificity.

PMID- 21096846
TI  - Supersampling in PET. A concept for improvement of the resolution of positron
      emission tomography.
AB  - At present, the maximum spatial resolution of state-of-the-art PET scanners is
      not better than 5 mm, whereas the maximum resolution obtained in the resulting
      images is approximately 10 mm. At least some of this difference is a result of an
      inherent, complex noise component that can be eliminated using "supersampling".
      The aim of the study was to apply the supersampling technique to PET image
      recordings to lower the noise and to improve the in-plane resolution of the
      recorded images. A standardized phantom was investigated with the supersampling
      technique. In addition to the standard CT and PET series, 14 further PET series
      were recorded with the phantom at exactly the same position, and 4 further series
      were recorded with the phantom placed in another well defined position. After
      merging corresponding images, the image noise index and the image resolution are
      both substantially improved. The suggested PET image recording and processing
      technique provides a substantial increase in PET image quality without exposing
      the patient to any additional radiation, and might therefore become a powerful
      tool for investigative as well as diagnostic purposes.

PMID- 21096847
TI  - New reconstruction algorithm, distance dependent exact, with reduced statistical
      alpha error, dedicated to emission tomography using a collimator with large and
      long holes.
AB  - SPECT (single photon emission computerized tomography) is physically one of the
      worst medical imaging modalities. Despite a considerable and still increasing
      medical impact, its spatial resolution (beyond 1 cm) and its sensitivity (less
      than 10(-4)) are both awful. This situation is mainly due to the use of a thin
      parallel hole collimator. In addition the application of the unfitted radon
      transform worsens the figure.

PMID- 21096848
TI  - New principles in nuclear medicine imaging: a full aperture stereoscopic imaging
      technique.
AB  - In nuclear medicine, images of planar scintigraphy and single photon emission
      computerized tomography (SPECT) obtained through gamma camera (GC) appear to be
      blurred. Alternatively, coded aperture imaging (CAI) can surpass the quality of
      GC images, but still it is not extensively used due to the decoding complexity of
      some images and the difficulty in controlling the noise. Summing up, the images
      obtained through GC are low quality and it is still difficult to implement CAI
      technique. Here we present a full aperture imaging (FAI) technique which
      overcomes the problems of CAI ordinary systems. The gamma radiation transmitted
      through a large single aperture is edge-encoded, taking advantage of the fact
      that nuclear radiation is spatially incoherent. The novel technique is tested by
      means of Monte Carlo method with simple and complex sources. Spatial resolution
      tests and parallax tests of GC versus FAI were made, and three-dimensional
      capacities of GC versus FAI were analyzed. Simulations have allowed comparison of
      both techniques under ideal, identical conditions. The results show that FAI
      technique has greater sensitivity (approximately 100 times) and greater spatial
      resolution (>2.6 times at 40 cm source-detector distance) than that of GC. FAI
      technique allows to obtain images with typical resolution of GC short source
      detector distance but at longer source-detector distance. The FAI decoding
      algorithm simultaneously reconstructs four different projections, while GC
      produces only one projection per acquisition. Our results show it is possible to
      apply an extremely simple encoded imaging technique, and get three-dimensional
      radioactivity information. Thus GC-based systems could be substituted, given that
      FAI technique is simple and it produces four images which may feed stereoscopic
      systems, substituting in some cases, tomographic reconstructions.

PMID- 21096849
TI  - A real-time cardiac surface tracking system using Subspace Clustering.
AB  - Catheter based radio frequency ablation of atrial fibrillation requires real-time
      3D tracking of cardiac surfaces with sub-millimeter accuracy. To best of our
      knowledge, there are no commercial or non-commercial systems capable to do so. In
      this paper, a system for high-accuracy 3D tracking of cardiac surfaces in real
      time is proposed and results applied to a real patient dataset are presented.
      Proposed system uses Subspace Clustering algorithm to identify the potential
      deformation subspaces for cardiac surfaces during the training phase from pre
      operative MRI scan based training set. In Tracking phase, using low-density outer
      cardiac surface samples, active deformation subspace is identified and complete
      inner & outer cardiac surfaces are reconstructed in real-time under a least
      squares formulation.

PMID- 21096850
TI  - Analysis of intracranial pressure recordings: comparison of PCA and signal
      averaging based filtering methods and signal period estimation.
AB  - Intracranial pressure monitoring is a common used approach for neuro-intensive
      care in cases of brain damages and injuries or to investigate chronic
      pathologies. Several types of noises and artifacts normally contaminate ICP
      recordings. They can be sorted in 2 classes, i.e. high-frequency noises (due to
      measurement and amplifier devices or electricity supply presence) and low
      frequency noises (due to unwanted patient's movement, speeches, coughing during
      the recording and quantization noise). Thus, deep investigations on ICP
      components aimed to extract features from ICP signal, require a denoised signal.
      For this reason the authors have addressed a study upon the most common filtering
      techniques. On each ICP recording we have performed 4 configurations of filters,
      which involve the use of a FIR filter together with Signal Averaging filters or
      PCA based filters. Next step is period estimation for absolute minima detection.
      The results obtained by the algorithm for automatic ICP marking are compared to
      those ones obtained from manual marking (peaks are manually identified and
      annotated by a brain surgeon). The procedure is repeated varying the filters
      sliding window size to minimize the mean square error. The results show how the
      configurations FIR filter + Signal averaging provides smaller mean squared error
      (MSE=118.84[sample(2)]) than the others 3 configurations FIR filter + PCA filter
      based (MSE=135.29-147.15[sample(2)]).

PMID- 21096851
TI  - Nonlinear feature extraction using kernel principal component analysis with non
      negative pre-image.
AB  - The inherent physical characteristics of many real-life phenomena, including
      biological and physiological aspects, require adapted nonlinear tools. Moreover,
      the additive nature in some situations involve solutions expressed as positive
      combinations of data. In this paper, we propose a nonlinear feature extraction
      method, with a non-negativity constraint. To this end, the kernel principal
      component analysis is considered to define the most relevant features in the
      reproducing kernel Hilbert space. These features are the nonlinear principal
      components with high-order correlations between input variables. A pre-image
      technique is required to get back to the input space. With a non-negative
      constraint, we show that one can solve the pre-image problem efficiently, using a
      simple iterative scheme. Furthermore, the constrained solution contributes to the
      stability of the algorithm. Experimental results on event-related potentials
      (ERP) illustrate the efficiency of the proposed method.

PMID- 21096852
TI  - Optimum principal components for spatial filtering of EEG to detect imaginary
      movement by coherence.
AB  - Several techniques have been used to improve the signal-to-noise ratio to
      increase the detection rate of Event Related Potentials (ERPs). This work
      investigates the application of spatial filtering based on principal component
      analysis (PCA) to detect ERP due to left-hand index finger movement imagination.
      The EEG signals were recorded of central derivations (C4, C2, Cz, C1 and C3),
      positioned according to 10-10 International System. The optimal spatial filter
      was found by using the first principal component and the ERP detection was
      obtained by magnitude squared coherence technique. The best detection rate, by
      using original signal (without filtering), was obtained at C2 derivation, with
      54.73% for significance level of 5%. For the same significance level, the
      detection rate of the filtered signal was drastically improved to 96.84%. Results
      suggest that spatial filter by using PCA might be a very useful tool in assisting
      the ERP detection for movement imagination for applications on brain machine
      interface.

PMID- 21096853
TI  - Gait initiation evaluation after deep brain stimulation for Parkinson's disease:
      A 7-year follow-up.
AB  - This study evaluated the long-term effects of deep brain stimulation of the
      subthalamic nucleus (DBS-STN) on gait initiation. Six Parkinson's disease (PD)
      patients who had undergone DBS-STN and 31 control subjects were evaluated. PD
      subjects were assessed at two different time periods: 11.3 +/- 10.3 (P1) and 78.9
      +/- 10.6 (P2) months after surgery. Subjects under stimulation were tested in two
      conditions: without medication and with medication. Principal components (PC)
      analysis was separately applied on vertical, anterior-posterior and medial
      lateral ground reaction force (GRF) from gait initiation, during the anticipatory
      postural adjustment (APA) phase. Three PC scores were chosen by the scree test
      for each GRF component. The higher loading factors pointed to major differences
      between controls and PD patients on maximum APA amplitude for vertical and
      anterior-posterior GRF. Friedman test showed a significant difference in standard
      distance among conditions (P = 0.006), with the post-hoc test recognizing
      differences only between P1 and P2 in the medication-on condition. All distances
      increased in the follow-up evaluation (P2), when considering the same medication
      condition, indicating a worsening in gait initiation after 7 years of follow-up.

PMID- 21096854
TI  - Acoustical detection of venous stenosis in hemodialysis patients using principal
      component analysis.
AB  - In this paper, a feature extraction method based on principal component analysis
      was developed for classification of the vascular access's condition in
      hemodialysis patients. The assessment of the method was carried out by
      discriminating between before and after angioplasty sound recordings as well as
      before angioplasty and reference recordings. The results showed that when before
      and after angioplasty recordings were compared by patient, the classification
      agreed with the result of angioplasty procedure. When all the available before
      and after angioplasty recordings were compared, it was still possible to
      discriminate them at a good rate. On the other hand, when the reference
      recordings substituted the after angioplasty recordings, almost a perfect
      discrimination was achieved.

PMID- 21096855
TI  - Non-negative blind source separation techniques for tumor tissue typing using HR
      MAS signals.
AB  - Given High Resolution Magic Angle Spinning (HR-MAS) signals from several
      glioblastoma tumor subjects, the goal is to differentiate between tumor tissue
      types by separating the different sources that contribute to the profile of each
      spectrum. Blind source separation techniques are applied for obtaining
      characteristic profiles for necrosis, high cellular tumor and border tumor
      tissue, and providing the contribution (abundance) of each tumor tissue to the
      profile of the spectra. The problem is formulated as a non-negative source
      separation problem. We illustrate the effectiveness of the proposed methods and
      we analyze to which extent the dimension of the input space could influence the
      performance by comparing the results on the full magnitude signals and on
      dimensionally reduced spaces.

PMID- 21096856
TI  - Gesture therapy: a vision-based system for upper extremity stroke rehabilitation.
AB  - Stroke is the main cause of motor and cognitive disabilities requiring therapy in
      the world. Therefor it is important to develop rehabilitation technology that
      allows individuals who had suffered a stroke to practice intensive movement
      training without the expense of an always-present therapist. We have developed a
      low-cost vision-based system that allows stroke survivors to practice arm
      movement exercises at home or at the clinic, with periodic interactions with a
      therapist. The system integrates a virtual environment for facilitating
      repetitive movement training, with computer vision algorithms that track the hand
      of a patient, using an inexpensive camera and a personal computer. This system,
      called Gesture Therapy, includes a gripper with a pressure sensor to include hand
      and finger rehabilitation; and it tracks the head of the patient to detect and
      avoid trunk compensation. It has been evaluated in a controlled clinical trial at
      the National Institute for Neurology and Neurosurgery in Mexico City, comparing
      it with conventional occupational therapy. In this paper we describe the latest
      version of the Gesture Therapy System and summarize the results of the clinical
      trail.

PMID- 21096857
TI  - A portable rehabilitation device for the Hand.
AB  - This paper presents the design of a direct driven under-actuated portable hand
      exoskeleton for rehabilitation. The design of the proposed Hand EXOskeleton
      SYStem (HEXOSYS) was driven by multi-objective optimisation strategy and
      inspiration from the human hand. The optimisation algorithm resulted in the
      choice of optimum link lengths of the device. The optimisation criteria are based
      on dexterity, isotropy and exertion of perpendicular forces on the finger digits.
      Furthermore, a series of experiments on the human hand using appropriate sensory
      instrumentation guided the selection of actuators thereby resulting in a
      rehabilitation device which is compatible with the human hand force capabilities.
      The provision of force as well as position feedback gives quantitative feedback
      to the therapist and would imply a more efficient rehabilitation process. The
      first prototype of the device has been designed and realized.

PMID- 21096858
TI  - Stabilizing unstable object by means of kinematic redundancy.
AB  - The paper aims to investigate how humans deal with unstable objects under the
      possibility of choosing different strategy of interaction. The presented task
      consisted in balancing a 1 degree of freedom (DoF) elastic inverted pendulum by
      means of 2 DoF of the wrist (fexion/extension and pronation/supination). The
      pendulum was simulated using a virtual environment and the haptic feedback was
      generated by a robotic wrist device. The task is a redundant because the subject
      can choose how to use the 2 DoF in order to move and stabilize a 1 DoF simulated
      mechanical system: the inverted pendulum. Six subjects volunteered to participate
      and were tested in four different days performing the same task but experiencing
      different mechanical systems (pendulum) characterized by lower or higher dynamics
      due to the possibility to tune the stiffness of the pendulum. Subjects were asked
      to balance the inverted pendulum maintaining it in a vertical position for a
      required amount of time. It was found the adopted stabilization strategy was
      mainly characterized by using only one of the 2 available DoFs of their wrist
      when the pendulum was stiffer, while in case of lower stiffness of the pendulum
      (slower dynamic) wrist input redundancy was a more suitable strategy to perform
      the balancing task.

PMID- 21096859
TI  - A prototype of a novel energy efficient variable stiffness actuator.
AB  - In this work, we present a proof of concept of a novel variable stiffness
      actuator. The actuator design is based on the conceptual design proposed in
      earlier work, and is such that the apparent output stiffness of the actuator can
      be changed independently of the output position and without any energy cost.
      Experimental results show that the behavior of the prototype is in accordance
      with the theoretical results of the conceptual design, and thus show that energy
      efficient variable stiffness actuators can be realized.

PMID- 21096860
TI  - Registration method for displaying electromagnetically tracked devices in
      fluoroscopic images.
AB  - Visualization of electromagnetically tracked instruments in pre- or intra
      interventional fluoroscopic images requires a registration process between the
      coordinate systems of both modalities. We present in this paper a new approach
      for performing this procedure by using only two external fiducial markers with
      integrated electromagnetic sensors which are applied on the patient's skin.
      Combined with the information acquired by the fluoroscopic system we achieve an
      automated and fast registration.

PMID- 21096861
TI  - Analysis of the relationship between interictal electrical source imaging and PET
      hypometabolism.
AB  - The aim of this paper is to compare interictal EEG source localizations with
      statistical analysis of hypometabolisms in PET brain imaging. Both methods are
      currently used in the pre-surgical evaluation of drug-resistant partial epilepsy,
      but the relationship between electrical source localizations and hypometabolic
      areas has not been well defined yet. At the present time, these two methods have
      been performed on five patients in order to develop a comparative quantitative
      study with these first results which should be then extended to a larger patient
      database.

PMID- 21096862
TI  - Medical image fusion using the convolution of Meridian distributions.
AB  - The aim of this paper is to introduce a novel non-Gaussian statistical model
      based approach for medical image fusion based on the Meridian distribution. The
      paper also includes a new approach to estimate the parameters of generalized
      Cauchy distribution. The input images are first decomposed using the Dual-Tree
      Complex Wavelet Transform (DT-CWT) with the subband coefficients modelled as
      Meridian random variables. Then, the convolution of Meridian distributions is
      applied as a probabilistic prior to model the fused coefficients, and the weights
      used to combine the source images are optimised via Maximum Likelihood (ML)
      estimation. The superior performance of the proposed method is demonstrated using
      medical images.

PMID- 21096863
TI  - Nanotechnology based targeted drug delivery.
AB  - NANOTECHNOLOGY is having a great impact on many industrial applications, such as
      manufacturing, semiconductors, nanostructured materials and biotechnology. As
      relates to the latter, nanobiotechnology focuses on the ability to work at the
      molecular and atomic level to fabricate structures combining biological materials
      and synthetic materials, taking into account engineering, physics, chemistry,
      genomics and proteomics. The main goals relate to biosensors, nanosized
      microchips, and more generally to medical applications at the molecular level.
      Nanotechnology has been recently extensively applied to treatment and diagnosis
      of diseases and the new term nanomedicine has been introduced, for which several
      definitions have so far been proposed [1]-[3] which focus on the use of
      engineered nano-devices and nanostructures for diagnosis and treatment. One of
      the key aspects of nanomedicine is targeted drug delivery by nanoscale drug
      carriers. At present, 95 % of all new potential therapeutics have poor pharmaco
      kinetics and biopharmaceutical properties, there is therefore a great need to
      develop drug delivery [4] systems that convey the therapeutically active
      molecules only to the site of action, without affecting other organs and tissues
      [5]. This allows to lower required doses of drugs and to increase their
      therapeutic indices and safety profiles. It is possible to fabricate
      nanoparticles or nanocapsules with different properties as relates to drug
      encapsulation and release. A great amount of nanoscale systems for drug delivery
      has been investigated; they include liposomes, dendrimers, quantum dots,
      nanotubes, polymeric biodegradable nanoparticles and nanocapsules [6].

PMID- 21096865
TI  - Effect of fluorescent tags on translocation through nanochannels.
AB  - The fluorescent tagging of biomolecules can have substantial effects on the
      charge distribution and translocation of the molecules through nanochannels. We
      show that the diffusion and calculated flux of translocating protein molecules
      through nanochannels are strong functions of the tags used. The size of the
      nanopore channels of a membrane also affect whether the channels provide
      facilitated transport or act just like affinity chromatography. These findings
      have important implications on micro/nanofluidic based biophysical studies that
      greatly discount the effects of tagged dyes on molecular transport and their
      mechanics.

PMID- 21096864
TI  - Effect of sustained release of bone morphogenetic protein on osteogenic
      expression of mesenchymal stem cells.
AB  - The objective of this work was to investigate the effect of sustained release of
      rhBMP-2, grafted to biodegradable nanoparticles (NPs) based on osteogenic
      differentiation of bone mesenchymal stem (BMS) cells. The release kinetics of
      rhBM-2 was linear with incubation time in the first two weeks. rhBMP-2 grafted
      NPs were as effective in inducing mineralization as the rhBMP-2 directly added to
      the culture media. rhBMP-2 grafted NPs had much higher expression of osteogenic
      markers osteopontin (OP) and osteocalcin (OC), compared to the protein directly
      added to culture media.

PMID- 21096866
TI  - Self-assembly and recrystallization of bacterial S-layer proteins of Bacillus
      sphaericus and Bacillus thuringiensis on silicone, mica and quartz crystal
      supports.
AB  - The Oriented architecture of macromolecules plays a critical role in many aspects
      of Nanobiotechnology such as in the development of biosensors. To this regard, S
      layers which constitute the outermost cell envelope component of many prokaryotic
      organisms, represent unique self assembled systems with the capability to
      rearrange into monomolecular and oriented arrays. These properties can be
      exploited to promote their crystallization on surfaces (e.g. silicone) which is
      pivotal for the subsequent immobilization of macromolecules and development of
      new biosensors. In this work the crystallization of bacterial S-layers obtained
      from Bacillus thuringiensis and Bacillus sphaericus CCM2177 on silicone, mica and
      quartz crystal surfaces were investigated. The SDS page results of S-layers
      isolated from the above mentioned bacteria put in evidence that their molecular
      weight (MW) was around 120 KDa and, as reported in the literature, slightly
      higher for those extracted by Bacillus thuringiensis. In addition, results showed
      that S-layers isolated from Bacillus thuringiensis form large crystalline domains
      on mica after 5 min whereas those extracted from Bacillus sphaericus CCM 2177
      form a compact monolayer on silicone after 2 h. Results in this work put in
      evidence the possibility to use these substrates for the fabrication of sensitive
      biosensors.

PMID- 21096867
TI  - Is a single cell sensor possible?
AB  - A cell-based implant is a miniaturized sensor that can be placed inside a
      biological living cell. This device would be able to interrogate and possibly
      affect biological functions in vivo. This paper explores the requirements of such
      a system; it also investigates the changes that need to be brought about in both
      fabrication technologies and design methodologies to make this visionary
      application a reality.

PMID- 21096868
TI  - Powering biomedical devices with body motion.
AB  - Energy harvesting from body motion is an alternative power source that can be
      used to energize miniature electronic biomedical devices. This technology can
      make it possible to recharge batteries to reduce the frequency of or eliminate
      surgeries to replace depleted cells. Power availability evaluation from walking
      and running at several body locations and different speeds is presented.
      Treadmill tests were performed on 11 healthy subjects to measure the
      accelerations at the ankle, knee, hip, chest, wrist, elbow, upper arm, and side
      of the head. Power was estimated from the treadmill results since it is
      proportional to the acceleration magnitudes and the frequency of occurrence.
      Available power output from walking was found to be more than 0.5 mW/cm(3) for
      all body locations while being more than 10 mW/cm(3) for the ankle and knee.
      Running results were at least 10 times higher than those from walking. An axial
      flux miniature electric dynamo using electromagnetic induction was evaluated for
      power generation. The device was composed of a rotor with multiple-pole permanent
      magnets positioned on an annular ring having an eccentric mass, and stacked
      planar coils as a stator. A 2 cm(3) prototype was found to generate 117 microW of
      power from the generator placed laterally on the ankle while walking.

PMID- 21096869
TI  - In-vitro platform to study ultrasound as source for wireless energy transfer and
      communication for implanted medical devices.
AB  - A platform to study ultrasound as a source for wireless energy transfer and
      communication for implanted medical devices is described. A tank is used as a
      container for a pair of electroacoustic transducers, where a control unit is
      fixed to one wall of the tank and a transponder can be manually moved in three
      axes and rotate using a mechanical system. The tank is filled with water to allow
      acoustic energy and data transfer, and the system is optimized to avoid parasitic
      effects due to cables, reflection paths and cross talk problems. A printed
      circuit board is developed to test energy scavenging such that enough acoustic
      intensity is generated by the control unit to recharge a battery loaded to the
      transponder. In the same manner, a second printed circuit board is fabricated to
      study transmission of information through acoustic waves.

PMID- 21096870
TI  - Mass casualty incident surveillance and monitoring using identity aware video
      analytics.
AB  - In this paper, we propose an identity aware video analytic system that can assist
      securing the perimeter of a mass casualty incident scene and generate identity
      annotated video records for forensics and training purposes. Establishing a
      secure incident scene perimeter and enforcing access control to different zones
      is a demanding task for current video surveillance systems which lack the ability
      to provide the identity of the target and its security clearance. Our system
      which combines active RFID sensors with video analytic tools recovers the
      identity of the target enabling the activation of suitable alert policies. The
      system also enables annotation of incident scene video with identity metadata,
      facilitating the incident response process reconstruction for forensics analysis
      and emergency response training.

PMID- 21096871
TI  - SHIMMER: an extensible platform for physiological signal capture.
AB  - Wireless sensor networks have become increasingly common in everyday applications
      due to decreasing technology costs and improved product performance, robustness
      and extensibility. Wearable physiological monitoring systems have been utilized
      in a variety of studies, particularly those investigating ECG or EMG during human
      movement or sleep monitoring. These systems require extensive validation to
      ensure accurate and repeatable functionality. Here we validate the physiological
      signals (EMG, ECG and GSR) of the SHIMMER (Sensing Health with Intelligence,
      Modularity, Mobility and Experimental Reusability) against known commercial
      systems. Signals recorded by the SHIMMER EMG, ECG and GSR daughter-boards were
      found to compare well to those obtained by commercial systems.

PMID- 21096872
TI  - Wireless medical sensor measurements of fatigue in patients with multiple
      sclerosis.
AB  - This paper presents our experience with developing a portable wireless medical
      sensor device. We use National Instruments (NI) devices and LabView for
      measurements studying fatigue of patients suffering multiple sclerosis (MS).
      Fatigue is a very frequent symptom perceived by MS patients, but the disease
      mechanism is poorly understood. Many efforts have been made to increase the
      understanding of this complex phenomenon. It has been found that fatigue might be
      associated with abnormalities in various anatomical brain areas. Also some
      secondary factors, not directly related to the disease, such as depression, sleep
      disorder, severe pain, use of medication and psychological factors might be of
      importance. However, the relationship with physiological parameters and motion
      activities in MS patients with fatigue across time are still unknown. Therefore,
      we hypothesize that we could provide a new assessment of fatigue in MS besides
      the questionnaires that are currently employed. Furthermore we can discover more
      secondary factors contributing to fatigue by measuring and monitoring a battery
      of physiological parameters over an extended time span (e.g. 48 hours) in MS
      patients without disturbing their normal life behavior. We have developed
      wireless medical sensor devices and conducted the following, namely
      Electrocardiograph, body skin temperature, eye movement detection,
      Electromyograph, motion detection, and muscle strength. In this paper, we
      describe the technology and design procedures of each measurement and present
      data from the first two test patients.

PMID- 21096873
TI  - RMAIS: RFID-based medication Adherence Intelligence System.
AB  - There has been compelling evidence that outpatients, especially those who are
      elderly or taking multiple complexly scheduled drugs, are not taking their
      medicines as directed, leading to unnecessary disease progression, complications,
      functional disabilities, lower quality of life, and even mortality. Existing
      technologies for monitoring and improving drug adherence are either costly or too
      complicated for general patients to use. In this paper, we introduce the detailed
      design and the complete prototype of a marketable Radio-Frequency Identification
      (RFID)-based Medication Adherence Intelligence System (RMAIS) that can be
      conveniently used at a residential home by ordinary patients. RMAIS is designed
      to maintain patients' independence and enable them to take multiple daily
      medicine dosages of the right amount at the right time. The system is patient
      centered and user-friendly by reminding a patient of the prescribed time for
      medication and dispensing it in a fully automatic and fool-proof way. This is
      achieved mainly due to its novel design of a motorized rotation platform and the
      smooth integration of a scale, an RFID reader, and the rotation platform. In
      addition, this system has an Internet-based notification function that is used to
      alert the patient when it is time to take medicine as well as report deviations
      from the prescribed schedule to the primary care physicians or pharmacists.

PMID- 21096874
TI  - Effect of the Valsalva maneuver on cardiac-coronary interaction assessed by wave
      intensity analysis.
AB  - The Valsalva maneuver (VM) provokes strong changes in the cardiovascular system
      and is therefore well suited to study the cardiac-coronary interaction in humans.
      In 12 patients undergoing catheterization we simultaneously recorded aortic
      pressure, left ventricular pressure, and intracoronary pressure (Pd) and flow
      velocity (U) while the patients were performing a VM. Coronary wave intensity was
      calculated (dI = dP*dU) at characteristic phases of the VM and related to
      hemodynamic parameters of left ventricular (LV) performance. During the strain,
      blood pressure increased transiently followed by a significant decrease (p <
      0.001) at maximum strain. Changes in mean LV pressure followed the same pattern,
      while LV end-diastolic pressure increased to almost 40 mmHg (p < 0.001), with a
      30% reduction in LV dP/dt (p < 0.005). Coronary flow velocity remained fairly
      constant throughout the VM. All hemodynamic values returned to the baseline at
      conclusion of the maneuver. Coronary wave intensity was strongly reduced during
      the strain and was related to the depression in LV performance. Wave intensity
      analysis clearly revealed the inherent features of cardiac-coronary interaction.

PMID- 21096875
TI  - Coronary flow reserve in mice: effects of age, coronary disease, and vascular
      loading.
AB  - Mice are now commonly used as models of human cardiovascular diseases and
      conditions, but it is challenging to measure blood flow velocity in small vessels
      such as coronary arteries. Accordingly, we have developed a method using a 2 mm
      diameter 20 MHz pulsed Doppler probe applied to the chest of an anesthetized
      mouse to measure left main coronary blood flow velocity noninvasively. We also
      found that coronary flow velocity could be increased from baseline (B) to
      hyperemic (H) levels by changing the concentration of isoflurane gas anesthesia
      from 1% to 2.5% in oxygen and that the H levels are similar to or higher than
      those induced by adenosine. We used the ratio H/B to estimate coronary flow
      reserve (CFR) in young, adult, and old mice and in mice with atherosclerosis,
      coronary occlusion, pressure overload, and angiotensin infusion. We found that
      H/B increases with age from 2.4 (young) to 3.6 (old) and is reduced by all forms
      of coronary and vascular disease to as low as 1.1 by pressure overload. We
      conclude that CFR can be measured noninvasively and serially in mice as their
      cardiovascular systems adapt and remodel to various imposed or natural
      conditions, and that left main coronary flow reserve may be a good index of
      global cardiac function.

PMID- 21096876
TI  - Noninvasive transthoracic and transesophageal Doppler echocardiographic
      measurements of human coronary blood flow velocity: In vitro flow phantom
      validation.
AB  - Coronary angiography is limited in assessing the hemodynamic significance of a
      coronary lesion or the state of the coronary microcirculation. Noninvasive
      transthoracic (TTE) and transesophageal (TEE) Doppler echocardiography have been
      used to measure coronary blood flow velocity and coronary flow reserve and thus
      the physiology of the coronary vasculature (normal, stable or unstable lesions).
      A fundamental, in vitro validation of these methods with a tissue and blood
      mimicking flow phantom has not been reported. Accordingly, Bland-Altman 95%
      confidence levels for precision (repeated measures) and accuracy (comparison with
      time collection) were determined for both TTE and TEE measurements of simulated
      coronary diastolic blood velocities in 2 mm and 4 mm vessels at the normal in
      vivo depths of 40 mm and 60 mm. The Doppler angle was set at 45 degrees and flow
      velocities were varied within a normal in vivo range of 0- 150 cm/s. Confidence
      levels for precisions and accuracies were similar between TTE and TEE and ranged
      from +/- 6 cm/s to +/- 13 cm/s or approximately 10-15% over the range of the
      measured velocities. These in vitro results in a controlled flow phantom suggest
      that technically adequate TTE and TEE can be used to reliably measure epicardial
      coronary conduit artery blood flow velocities.

PMID- 21096877
TI  - A patient-specific method for the evaluation of wall shear stress in human
      coronary arteries.
AB  - Atherosclerotic plaques form at specific sites of the arterial tree, an
      observation that has led to the "geometric risk factor" hypothesis for
      atherogenesis. It is accepted that the location of atherosclerotic plaques is
      correlated with sites subjected to low abnormal values of wall shear stress
      (WSS), which is in turn determined by the specific geometry of the arterial
      segment. In particular, the left coronary artery (LCA) is one of the most
      important sites of plaque formation and its progression may lead to stroke.
      However, little is known about hemodynamics and WSS distributions in the LCA. The
      purpose of this work is to set up a method to evaluate flow patterns and WSS
      distributions in the human LCA based on real patient-specific geometries
      reconstructed from medical images.

PMID- 21096878
TI  - Mechanical properties of human coronary arteries.
AB  - The lack of reliable mechanical data on coronary arteries and, more specifically,
      on their wall strength hampers the application of numerical models and
      simulations to vascular problems, and precludes physicians from knowing in
      advance the response of coronary arteries to the different interventions. Studies
      of the mechanical properties of coronary arteries have been carried out almost
      exclusively on animals. Only a few studies have tried to characterize the in vivo
      behavior of human coronaries through tests under physiological conditions. In
      this work, the mechanical properties of human coronary arteries have been
      characterized. Whole samples from human right (RC) and left anterior descending
      (LAD) coronary arteries aged between 23 and 83 years have been studied by means
      of in-vitro tensile testing up to failure.

PMID- 21096879
TI  - Study of the autonomic response in hemodialysis patients with different fluid
      overload levels.
AB  - This work aims at studying the autonomic nervous system (ANS) response to
      hemodialysis (HD) treatment in a population of end stage renal disease (ESRD)
      patients. ECG Holter recordings and whole body bioimpedance spectroscopy
      measurements were performed for each patient. Patients were classified according
      to the fluid overload (FO) values and the systolic blood pressure (SBP) measured
      before HD. Time domain and frequency domain indices from heart rate variability
      (HRV) signals were measured for the first 30 minutes and last 30 minutes of HD,
      the first hour after HD, and night (12.00 p.m.-4 a.m.). Significant differences
      were obtained in fluid overloaded but normotensive patients (Group IV) with
      respect to fluid overloaded and hypertensive patients (Group I) and normohydrated
      and normotensive patients (Group N+Dx). In particular, SDNN, RMSSD, SDSD, pNN50%,
      indices resulted significantly higher in Group IV with respect to the other
      groups. Overhydrated patients with hypertension (Group I) showed a blunted
      parasympathetic activity, which is supposed to contribute to hypertension.

PMID- 21096880
TI  - Nonlinear analysis of movement-related changes in human subthalamic local field
      potentials.
AB  - Movement-related changes such as event-related desynchronizationcan (ERD) and
      event-related synchronization (ERS) can be found in human subthalamic nucleus
      (STN) with analysis on local field potentials (LFP) recorded from Parkinson's
      disease (PD) patients. Besides traditional time-frequency (TF) analysis, we
      introduced nonlinear analysis, bispectral and approximate entropy (ApEn), to
      measure the signal nonlinear correlation and regularity in neural activities.
      Movement-related changes were found in the beta band, bicoherence and ApEn, and
      variation during stationary movement is more available by nonlinear methods.
      Therefore, we suggest nonlinear analysis for further related studies.

PMID- 21096881
TI  - Neuronal functional connectivity dynamics in cortex: An MSC-based analysis.
AB  - The activation of neural ensembles in the cortex is correlated with behavioral
      states and a change in neuronal functional connectivity patterns is expected. In
      this paper, we investigate this dynamic nature of functional connectivity in the
      cortex. Because of the time scale of behavior, a robust method with limited
      sample size is desirable. In light of this, we utilize mean square contingency
      (MSC) to measure the pairwise neural dependency to quantify the cortical
      functional connectivity. Simulation results show that MSC is more robust than
      cross correlation when the sample size is small. In monkey neural data test, our
      approach is more effective in detecting the dynamics of functional connectivity
      associated with the transitions between rest and movement states.

PMID- 21096882
TI  - Analysis of neural interaction in motor cortex during reach-to-grasp task based
      on Dynamic Bayesian Networks.
AB  - In this work, we took the analysis of neural interaction based on the data
      recorded from the motor cortex of a monkey, when it was trained to complete multi
      targets reach-to-grasp tasks. As a recently proved effective tool, Dynamic
      Bayesian Network (DBN) was applied to model and infer interactions of dependence
      between neurons. In the results, the gained networks of neural interactions,
      which correspond to different tasks with different directions and orientations,
      indicated that the target information was not encoded in simple ways by neuronal
      networks. We also explored the difference of neural interactions between delayed
      period and peri-movement period during reach-to-grasp task. We found that the
      motor control process always led to relatively more complex neural interaction
      networks than the plan thinking process.

PMID- 21096883
TI  - Real-time experiment interface for biological control applications.
AB  - The Real-time Experiment Interface (RTXI) is a fast and versatile real-time
      biological experimentation system based on Real-Time Linux. RTXI is open source
      and free, can be used with an extensive range of experimentation hardware, and
      can be run on Linux or Windows computers (when using the Live CD). RTXI is
      currently used extensively for two experiment types: dynamic patch clamp and
      closed-loop stimulation pattern control in neural and cardiac single cell
      electrophysiology. RTXI includes standard plug-ins for implementing commonly used
      electrophysiology protocols with synchronized stimulation, event detection, and
      online analysis. These and other user-contributed plug-ins can be found on the
      website (http://www.rtxi.org).

PMID- 21096884
TI  - A subthreshold aVLSI implementation of the Izhikevich simple neuron model.
AB  - We present a circuit architecture for compact analog VLSI implementation of the
      Izhikevich neuron model, which efficiently describes a wide variety of neuron
      spiking and bursting dynamics using two state variables and four adjustable
      parameters. Log-domain circuit design utilizing MOS transistors in subthreshold
      results in high energy efficiency, with less than 1pJ of energy consumed per
      spike. We also discuss the effects of parameter variations on the dynamics of the
      equations, and present simulation results that replicate several types of neural
      dynamics. The low power operation and compact analog VLSI realization make the
      architecture suitable for human-machine interface applications in neural
      prostheses and implantable bioelectronics, as well as large-scale neural
      emulation tools for computational neuroscience.

PMID- 21096885
TI  - RatCar: A vehicular neuro-robotic platform for a rat with a sustaining structure
      of the rat body under the vehicle.
AB  - An online neuro-robotic platform in the form of a small vehicle, the "RatCar" has
      been developed. First, a rat had neural electrodes implanted in the motor
      cortices to record extracellular potentials. Then, our system combined the rat
      and its vehicle body by hanging the rat under its floor. In this paper, an
      experimental platform is proposed to observe and analyze motor commands by
      correlating neural signals with locomotion states. It was designed to operate in
      2 modes; (a) adaptively correlating neural signals and locomotion states to
      determine motor commands, and (b) applying the estimated motor commands to
      control the vehicle according to the intention of the rat. As a result, time
      varying correlation between neural and locomotion activities has been adaptively
      visualized in real time to analyze motor commands in various body conditions. In
      addition, a control of the vehicle has been improved.

PMID- 21096886
TI  - In search of more robust decoding algorithms for neural prostheses, a data driven
      approach.
AB  - In the past decade the field of neural interface systems has enjoyed an increase
      in attention from the scientific community and the general public, in part due to
      the enormous potential that such systems have to increase the quality of life for
      paralyzed patients. While significant progress has been made, serious challenges
      remain to be addressed from both biological and engineering perspectives. A key
      issue is how to optimize the decoding of neural information, such that neural
      signals are correctly mapped to effectors that interact with the outside world -
      like robotic hands and limbs or the patient's own muscles. Here we present some
      recent progress on tackling this problem by applying the latest developments in
      machine learning. Neural data was collected from macaque monkeys performing a
      real-time hand grasp decoding task. Signals were recorded via chronically
      implanted electrodes in the anterior intraparietal cortex (AIP) and ventral
      premotor cortex (F5), brain areas that are known to be involved in the
      transformation of visual signals into hand grasping instructions. We present a
      comparative study of different classical machine learning methods with an
      application of decoding of hand postures, as well as a new approach for more
      robust decoding. Results suggests that combining data-driven algorithmic
      approaches with well-known parametric methods could lead to better performing and
      more robust learners, which may have direct implications for future clinical
      devices.

PMID- 21096887
TI  - Towards a brain controlled assistive technology for powered mobility.
AB  - For individuals with mobility limitations, powered wheelchair systems provide
      improved functionality, increased access to healthcare, education and social
      activities. Input devices such as joystick and switches can provide the necessary
      input required for efficient control of the powered wheelchair. For persons with
      limited dexterity, or fine control of the fingers, access to mechanical hardware
      such as buttons and joysticks can be quite difficult and sometimes painful. For
      individuals with conditions such as Traumatic Brain Injury (TBI), Multiple
      Sclerosis (MS) or Amyotrophic lateral sclerosis (ALS) voluntary control of limb
      movement maybe substantially limited or completely absent. Brain Computer
      Interfaces (BCI) are emerging as a possible method to replace the brains normal
      output pathways of peripheral nerves and muscles, allowing individuals with
      paralysis a method of communication and computer control. This study involves the
      analysis of non-invasive electroencephalograms (EEG) arising from the use of a
      newly developed Human Machine Interface (HMI) for powered wheelchair control.
      Using a delayed response task, binary classification of left and right movement
      intentions were classified with a best classification rate of 81.63% from single
      trial EEG. Results suggest that this method may be used to enhance control of
      HMI's for individuals with severe mobility limitations.

PMID- 21096888
TI  - Single trial recognition of error-related potentials during observation of robot
      operation.
AB  - Recent works suggest that several human cognitive processes elicited during the
      observation and monitoring of tasks developed by others can be detected in real
      time. These works have also demonstrated that human brain activity can be used to
      recover from machine errors, and as reward signals to teach a simulated robot how
      to perform given tasks. This paper studies the elicitation of this activity
      during the operation of a real robot. Experimental results have been obtained
      with 4 participants observing the operation of a 5 d.o.f. robotic arm performing
      correct/incorrect reaching tasks, while an EEG system recorded their brain
      activity. The results give evidence that the brain areas that play a role in
      detection and monitoring of errors also play a role when observing the operation
      of a real robot, that a brain discriminative response is elicited during the
      observation of a correct/incorrect operation of a real robot, and that it is
      possible to learn a classifier that provides online categorization with high
      accuracy (80%).

PMID- 21096889
TI  - Two-dimensional auditory p300 speller with predictive text system.
AB  - P300-based Brain Computer Interfaces offer communication pathways which are
      independent of muscle activity. Mostly visual stimuli, e.g. blinking of different
      letters are used as a paradigm of interaction. Neural degenerative diseases like
      amyotrophic lateral sclerosis (ALS) also cause a decrease in sight, but the
      ability of hearing is usually unaffected. Therefore, the use of the auditory
      modality might be preferable. This work presents a multiclass BCI paradigm using
      two-dimensional auditory stimuli: cues are varying in pitch (high/medium/low) and
      location (left/middle/right). The resulting nine different classes are embedded
      in a predictive text system, enabling to spell a letter with a 9-class decision.
      Moreover, an unbalanced subtrial selection is investigated and compared to the
      well-established sequence-wise paradigm. Twelve healthy subjects participated in
      an online study to investigate these approaches.

PMID- 21096890
TI  - Exploring multiple protocols for a brain-computer interface mouse.
AB  - In recent years, various visual protocols have been explored for P300-based BCI.
      In stimulus-driven BCI paradigms such as P300 BCIs it is vital to optimise the
      stimulation protocol as much as possible in order to achieve the best
      performance. Due to the inherent variability between subjects and the complex
      nature of the brain it is unlikely that an optimal protocol will be identified
      through a single iteration of random exploration. That is why in this paper we
      explore 8 different visual protocol configurations based on recent literature, in
      the hope of identifying key features that can later be used to create further
      improved protocols. Results indicate that luminosity changes, the standard method
      of stimulation used in visual P300 BCI protocols, do provide the best performance
      of the variations presented here.

PMID- 21096891
TI  - A versatile hardware platform for brain computer interfaces.
AB  - This article presents the development of a versatile hardware platform for brain
      computer interfaces (BCI). The aim of this work is to produce a small, autonomous
      and configurable BCI platform adaptable to the user's needs.

PMID- 21096892
TI  - A low-power, wireless, 8-channel EEG monitoring headset.
AB  - Micro- and nano-technology has enabled development of smaller and smarter
      wearable devices for medical and lifestyle related applications. In particular,
      recent advances in EEG monitoring technologies pave the way for wearable,
      wireless EEG monitoring devices. Here, a low-power wireless EEG sensor platform
      that measures 8-channels of EEG, is described. The platform is integrated into a
      wearable headset for ambulatory monitoring of EEG. While using standard EEG
      electrodes without conductive gel, a first evaluation shows the wireless headset
      is comparable to the reference system when looking at alpha wave discrimination.
      This device combines low-noise, and low-power functionality into an easy-to-use
      wireless headset, providing a first step towards a fully integrated, fully
      functional wearable wireless EEG monitoring system.

PMID- 21096893
TI  - Toward BCI Wizard - best BCI approach for each user.
AB  - Modern brain-computer interface (BCI) systems use different types of neural
      activity for control. Most BCI systems only allow the customization of very few
      parameters and focus only on one type of BCI approach. Many articles reported
      that a certain BCI did not work for some users (so called BCI illiteracy). We are
      introducing the BCI wizard as a system that automatically identifies key
      parameters to customize the best BCI paradigm for each user. With a BCI wizard it
      is possible to develop an interface that relies on the best mental strategy for
      each user and therefore makes the difference between an ineffective system and a
      working BCI. This work presents a preliminary study that aims to develop a BCI
      wizard exploring the two most effective BCI approaches (SSVEP and P300). These
      types of non-invasive BCIs were tested and evaluated in a group of 14 healthy
      subjects. During online tests all subjects were asked to spell three words with
      two spelling applications and at the end of the experiment they chose their
      preferred approach. Results showed that all subjects could communicate with the
      P300-based BCI with an accuracy above 69% (5 reached 100% accuracy), 10 out of 14
      subjects could effectively use the SSVEP-based BCI (2 reached 100% accuracy).
      These promising results confirm that BCI wizard will enable BCIs customized to
      each user with considerably greater flexibility and independence than present
      systems allow.

PMID- 21096894
TI  - A hybrid BCI system for 2-D asynchronous cursor control.
AB  - In this paper, a hybrid EEG-based brain computer interface (BCI) is designed for
      two-dimensional cursor control. In our approach, two brain activity patterns,
      i.e., motor imagery and P300 potential, are used for controlling the horizontal
      and the vertical movements of the cursor respectively. A real-time BCI system
      based on this approach is implemented and evaluated through an online experiment.
      Six subjects attending this experiment can perform 2-D cursor control
      effectively. Our experimental results show that the system has the following
      merits compared with prior systems: 1) it does not rely on intensive user
      training; 2) it allows cursor movement between arbitrary positions.

PMID- 21096896
TI  - Acquisition of action potentials with ultra-low sampling rates.
AB  - We introduce finite rate of innovation (FRI) based spike acquisition, a new
      approach to the sampling of action potentials. Drawing from emerging theory on
      sampling FRI signals, our process aims to acquire the precise shape and timing of
      spikes from electrodes with single or multiunit spiking activity using sampling
      rates of 1000 Hz or less. The key insight is that action potentials are
      essentially stereotyped pulses that are generated by neurons at a rate limited by
      an absolute refractory period. We use this insight to push sampling below the
      Nyquist rate. Our process is a parametric method distinct from compressed sensing
      (CS). In its full implementation, this process could improve spike-based devices
      for neuroscience and medicine by reducing energy consumption, computational
      complexity, and hardware demands.

PMID- 21096895
TI  - A zero-training algorithm for EEG single-trial classification applied to a face
      recognition ERP experiment.
AB  - This paper proposes a machine learning based approach to discriminate between EEG
      single trials of two experimental conditions in a face recognition experiment.
      The algorithm works using a single-trial EEG database of multiple subjects and
      thus does not require subject-specific training data. This approach supports the
      idea that zero-training classification and on-line detection Brain Computer
      Interface (BCI) systems are areas with a significant amount of potential.

PMID- 21096897
TI  - A study on EEG quality in physical movements with Steady-State Visual Evoked
      Potentials.
AB  - In this paper, we investigated the quality of ElectroEncephaloGraphic (EEG)
      signals during performing physical movements. By using a portable EEG device, the
      Steady-State Visual Evoked Potential (SSVEP) was recorded on parietal and
      occipital locations. The SSVEP induced by flickering stimuli was successfully
      observed in the self-paced mimic walking conditions as well as in the sitting
      conditions. To see the dependence of temporal and spatial filters on the
      potential performance of Brain-Computer Interfaces (BCI) we applied the signal
      processing of Principal Component Analysis and Linear Discriminant Analysis. The
      pattern recognition performances in inferring the subject's eye gaze directions
      from the EEG signals could be perfect even in the self-paced mimic walking
      conditions. It was found that three electrodes on parieto-occipital and occipital
      locations were essential in order to have perfect performances. From these
      results, we conclude that the applications using SSVEP-based BCI can be realized
      even in the physically moving context.

PMID- 21096898
TI  - BCI control using 4 direction spatial visual attention and real-time fMRI at 7T.
AB  - The goal of Brain-Computer-Interface (BCI) technologies is to "outsource" the
      muscular control to a computer and create new communication channels, e.g. to
      people with severe paralysis, by measuring cortical activation changes and
      linking these changes to commands. Using real-time fMRI at 7T we show that
      visuospatial attention can be used to reliably regulate cortical activity and
      that it is possible to separate the cortical responses to multiple attention
      target regions in real time. The activated regions were first located on the fly
      using an incremental statistical analysis and the subjects were then given
      feedback based on the activity in these regions. Visuospatial attention is an
      attractive addition to the existing BCI control strategies, and the fact that it
      leaves the motor system still available makes it suitable also for applications
      aimed for healthy people.

PMID- 21096899
TI  - Adaptation of hybrid human-computer interaction systems using EEG error-related
      potentials.
AB  - Performance improvement in both humans and artificial systems strongly relies in
      the ability of recognizing erroneous behavior or decisions. This paper, that
      builds upon previous studies on EEG error-related signals, presents a hybrid
      approach for human computer interaction that uses human gestures to send commands
      to a computer and exploits brain activity to provide implicit feedback about the
      recognition of such commands. Using a simple computer game as a case study, we
      show that EEG activity evoked by erroneous gesture recognition can be classified
      in single trials above random levels. Automatic artifact rejection techniques are
      used, taking into account that subjects are allowed to move during the
      experiment. Moreover, we present a simple adaptation mechanism that uses the EEG
      signal to label newly acquired samples and can be used to re-calibrate the
      gesture recognition system in a supervised manner. Offline analysis show that,
      although the achieved EEG decoding accuracy is far from being perfect, these
      signals convey sufficient information to significantly improve the overall system
      performance.

PMID- 21096900
TI  - A novel co-locational and concurrent fNIRS/EEG measurement system: design and
      initial results.
AB  - We describe here the design, set-up and first time classification results of a
      novel co-locational functional Near-Infrared Spectroscopy/Electroencephalography
      (fNIRS/EEG) recording device suitable for brain computer interfacing applications
      using neural-hemodynamic signals. Our dual-modality system recorded both
      hemodynamic and electrical activity at seven sites over the motor cortex during
      an overt finger-tapping task. Data was collected from two subjects and classified
      offline using Linear Discriminant Analysis (LDA) and Leave-One-Out Cross
      Validation (LOOCV). Classification of fNIRS features, EEG features and a
      combination of fNIRS/EEG features were performed separately. Results illustrate
      that classification of the combined fNIRS/EEG feature space offered average
      improved performance over classification of either feature space alone. The
      complementary nature of the physiological origin of the dual measurements offer a
      unique and information rich signal for a small measurement area of cortex. We
      feel this technology may be particularly useful in the design of BCI devices for
      the augmentation of neurorehabilitation therapy.

PMID- 21096901
TI  - Post-acute stroke patients use brain-computer interface to activate electrical
      stimulation.
AB  - Through certain mental actions, our electroencephalogram (EEG) can be regulated
      to operate a brain-computer interface (BCI), which translates the EEG patterns
      into commands that can be used to operate devices such as prostheses. This allows
      paralyzed persons to gain direct brain control of the paretic limb, which could
      open up many possibilities for rehabilitative and assistive applications. When
      using a BCI neuroprosthesis in stroke, one question that has surfaced is whether
      stroke patients are able to produce a sufficient change in EEG that can be used
      as a control signal to operate a prosthesis.

PMID- 21096902
TI  - Characteristics of motor imagery based EEG-brain computer interface using
      combined cue and neuro-feedback.
AB  - In this paper, we evaluated BCI algorithm using CSP for finding out about
      realistic possibility of BCI based on CSP. BCI algorithm that was comprised of
      CSP and least square linear classifier was evaluated in 10 persons. According to
      the result of the experiment, the effect of combined cue and neurofeedback is
      evaluated. In case of combined cue, the correlation of combined cue and visual
      cue is higher than other conditions. And in case of neurofeedback, some subject
      is exceptional but general trend shows the performance improvement by
      neurofeedback.

PMID- 21096903
TI  - Exploring preprocessing techniques in a three-class brain-machine interface.
AB  - In this work, we implemented a brain-machine interface (BMI) based on
      electroencephalographic (EEG) signals and used it to classify and separate three
      types of mental tasks: motor imagery with the right and left hands and simple
      arithmetic sums. In order to reduce dimension of variables and increase
      classification power, we used both PCA and ICA based algorithms for spectral
      analysis. Our results show that we were no able to reduce dimension without
      reducing classification performance.

PMID- 21096904
TI  - Assessment of nonlinear interactions in event-related potentials (ERPs) elicited
      by stimuli presented at short inter-stimulus intervals.
AB  - The recording of brain event-related potentials (ERPs) is a widely used technique
      to investigate the neural basis of sensory perception and cognitive processing in
      humans.. However, when the temporal interval between two consecutive stimuli used
      to elicit ERPs is smaller than the latency of the main ERP peaks, i.e., when the
      stimuli are presented at a fast rate, overlaps between the ERPs elicited by
      successive stimuli may occur. These overlaps are usually dealt with by assuming
      that there is no nonlinear interaction between these responses, and thereby by
      performing algebraic waveform subtractions. Here we propose a straightforward
      approach to assess the presence of nonlinear interactions in a ERPs. This
      approach is a direct consequence of the concept of nonlinearity between two
      successive impulsive-like stimuli. By applying this approach to ERPs elicited by
      nociceptive cutaneous stimuli delivered at inter-stimulus intervals (ISIs)
      ranging from 250 ms to 2000 ms, we provide evidence that there are no nonlinear
      interactions between nociceptive ERPs, even at the shortest ISIs.

PMID- 21096905
TI  - Controlling swing foot center of mass and toe trajectory to minimize tripping
      risk.
AB  - Swing toe trajectory has been investigated due to its association with tripping
      induced falls. This study investigated how motion of the entire foot segment
      influences the toe trajectory. Seven young and seven older participants walked
      both over-ground and on a treadmill to obtain the swing foot trajectory data. No
      ageing effects were obtained for toe trajectory control. Older adults were found
      to have greater asymmetry at minimum ground clearance, especially in treadmill
      walking, whereas foot center of mass (COM) control was symmetrical, suggesting
      that foot COM motion does not influence toe trajectory. Correlation analysis
      indicated that foot COM and toe trajectory may be controlled independently due to
      ankle motions that modulate the toe's elevation, a finding that has implications
      for falls prevention strategies. The results also provide the first report of the
      foot's center of mass trajectory during the swing phase of the gait cycle. The
      foot's trajectory resembles pendulum motion but further work will be necessary to
      test the foot-pendulum control hypothesis.

PMID- 21096906
TI  - Energy expenditure during human gait. II - Role of muscle groups.
AB  - A phenomenological model of muscle energy expenditure developed in part I of the
      paper, is utilized as a physiological cost function to estimate the muscle forces
      during normal locomotion. The model takes into account muscular behaviors
      typically observed during human gait, such as submaximal activation, variable
      muscular contraction conditions and muscular fiber type. The solution of the
      indeterminate biomechanical problem is obtained by integrating multibody dynamics
      and the global static optimization technique that considers the whole motion. The
      results for an application case indicate the important role of muscle groups in
      coordinating multijoint motion with the objective of minimizing metabolic costs
      of transport during locomotion.

PMID- 21096907
TI  - Fasciated nerve-muscle explants for in vitro comparison of magnetic and
      electrical neuromuscular stimulation.
AB  - Neuromuscular stimulation has become a central technique for research and
      clinical efforts in rehabilitation, but available devices still do not show the
      needed performance in strength and selectivity for this approach. However, the
      knowledge about the exact intramuscular structure formed by the axons, muscle
      fibers with their different metabolism types and properties as well as the
      motoric endplates in between is still too rough for purely theoretical
      optimization. In this text, we present an experimental setup for parametrized
      studies of the spatial and temporal degrees of freedom (DOF) in electrical as
      well as magnetic stimulation. For clarification of the physiologic background,
      nerve-muscle explants are dissected and kept on life support in a nutrient system
      with glucose and oxygen supply. The setup provides two-channel EMG signals and a
      dynamic force signal. The design was adapted to meet the conditions for physical
      compatibility with magnetic stimulation and allows coil position sweeps with four
      (three translational and one rotational) DOF. The setup provides access to
      essential boundary conditions and means to simulate lesions as well as the
      influence of drugs. Besides with the presented setup, comparisons and even
      combined application of magnetic and electrical stimulation become possible on
      the level of the neuromuscular system. Finally, this approach shall help to
      improve rehabilitation by peripheral stimulation after nerve lesions. The focus
      of this text lies on the setup and the nutrition which will entail particular
      studies in the sequel.

PMID- 21096908
TI  - An EMG-driven musculoskeletal model for the estimation of biomechanical
      parameters of wrist flexors.
AB  - A musculoskeletal model of wrist flexors comprising musculoskeletal dynamics and
      limb anatomy was experimentally validated with healthy subjects during maximum
      voluntary contractions. Electromyography signals recorded from flexors were used
      as input, while measured torques exerted by the hand were compared to the torques
      predicted by the model. The root mean square error and the normalized root mean
      square error calculated during estimation and validation phases were compared. In
      total, six subject-specific musculoskeletal parameters were estimated, while
      biomechanical indexes such as the operating range of the flexors, the stiffness
      of the wrist flexion musculotendon actuators, and the contribution of the muscle
      fibers to the joint moment were computed. Results are in agreement with
      previously published data.

PMID- 21096909
TI  - Towards error-free interaction.
AB  - Human-machine interaction (HMI) relies on pat- tern recognition algorithms that
      are not perfect. To improve the performance and usability of these systems we can
      utilize the neural mechanisms in the human brain dealing with error awareness.
      This study aims at designing a practical error detection algorithm using
      electroencephalogram signals that can be integrated in an HMI system. Thus, real
      time operation, customization, and operation convenience are important. We
      address these requirements in an experimental framework simulating machine
      errors. Our results confirm the presence of brain potentials related to
      processing of machine errors. These are used to implement an error detection
      algorithm emphasizing the differences in error processing on a per subject basis.
      The proposed algorithm uses the individual best bipolar combination of electrode
      sites and requires short calibration. The single-trial error detection
      performance on six subjects, characterized by the area under the ROC curve ranges
      from 0.75 to 0.98.

PMID- 21096910
TI  - A comparison of monopolar and bipolar EEG recordings for SSVEP detection.
AB  - This paper presents a comparative study over the detection of Steady-State Visual
      Evoked Potential (SSVEP) with monopolar or bipolar electroencephalographic (EEG)
      recordings in a Brain-Computer Interface experiment. Five subjects participated
      in this study. They were stimulated with four flickering lights at 13, 14, 15 and
      16 Hz and the EEG was measured simultaneously with two bipolar channels (O(1)
      P(3) and O(2)-P(4)) and with six monopolar channels at O(1), O(2), P(3), P(4),
      T(5) and T(6) referenced to F(Z). The EEG was processed by means of spectral
      analysis and the estimation of power at each stimulation frequency and its
      harmonics. In average, the monopolar recordings present accuracy in
      classification of 74.5% against an 80.1% for bipolar recordings. It was found
      that bipolar recording are better than monopolar recordings for detection of
      SSVEP.

PMID- 21096911
TI  - Single-trial classification of auditory event-related potentials elicited by
      stimuli from different spatial directions.
AB  - This study is focused on the single-trial classification of auditory event
      related potentials elicited by sound stimuli from different spatial directions.
      Five naiotave subjects were asked to localize a sound stimulus reproduced over
      one of 8 loudspeakers placed in a circular array, equally spaced by 45 degrees .
      The subject was seating in the center of the circular array. Due to the
      complexity of an eight classes classification, our approach consisted on feeding
      our classifier with two classes, or spatial directions, at the time. The seven
      chosen pairs were 0 degrees , which was the loudspeaker directly in front of the
      subject, with all the other seven directions. The discrete wavelet transform was
      used to extract features in the time-frequency domain and a support vector
      machine performed the classification procedure. The average accuracy over all
      subjects and all pair of spatial directions was 76.5%, sigma = 3.6. The results
      of this study provide evidence that the direction of a sound is encoded in single
      trial auditory event-related potentials.

PMID- 21096912
TI  - Mutual information-based Fisher discriminant analysis for feature extraction and
      recognition with applications to medical diagnosis.
AB  - This paper presents a novel discriminant analysis (DA) for feature extraction
      using mutual information (MI) and Fisher discriminant analysis (MI-FDA). Most DA
      algorithms for feature extraction are based on a transformation which maximizes
      the between-class scatter and minimizes the within-class scatter. In contrast,
      the proposed method uses the Fisher's criterion to find a transformation that
      maximizes the MI between the transferred features and the target classes and
      minimizes the redundancy. The performance of the proposed method is evaluated
      using UCI databases and compared with the performance of some DA-based
      algorithms. The results indicate that MI-FDA provides a robust performance over
      different data sets with different characteristics. On average, an accuracy rate
      of 81.3% was achieved using MI-FDA.

PMID- 21096913
TI  - Prototype of a wearable system for remote fetal monitoring during pregnancy.
AB  - Fetal Heart Rate (FHR) monitoring gives important information about the fetus
      health state during pregnancy. This paper presents a new prototype for remote
      fetal monitoring. The device will allow to monitor FHR in a domiciliary context
      and to send fetal ECG traces to a hospital facility, where clinicians can
      interpret them. In this way the mother could receive prompt feedback about fetal
      wellbeing. The system is characterized by two units: (i) a wearable unit endowed
      with textile electrodes for abdominal ECG recordings and with a Field
      Programmable Gate Array (FPGA) board for fetal heart rate (FHR) extraction; (ii)
      a dock station for the transmission of the data through the telephone line. The
      system will allow to reduce costs in fetal monitoring, improving the assessment
      of fetal conditions. The device is actually in development state. In this paper,
      the most crucial aspects behind its fulfillment are discussed.

PMID- 21096915
TI  - The influence of orthopaedic implants on patient tolerance of neuromuscular
      electrical stimulation (NMES).
AB  - Neuromuscular electrical stimulation (NMES) is a potential deep vein thrombosis
      (DVT) preventative measure that is often over-looked. NMES could be used
      postoperatively in conjunction with pharmacological prophylaxis to further reduce
      the incidence rate of DVT following orthopaedic surgery. However, the use of NMES
      in the recovery period following orthopaedic surgery on patients with metallic
      hip/knee implants has not been tested to date. The presence of a metallic implant
      may interfere with the NMES generated electric field causing hypersensitivity at
      the implant site. This may essentially limit the use of NMES postoperatively.
      Consequently, patient tolerance of NMES must be assessed before any treatment can
      be administered. Five hip replacement patients and 5 knee replacement patients
      participated in this study that were at least 3 weeks post-op. NMES was applied
      to the calf muscles of each patient using skin surface electrodes and the
      stimulation intensity was slowly increased. Comfort was assessed by asking the
      patient to indicate the stimulation intensity corresponding to 4 thresholds: when
      they first felt the stimulus sensation (sensory threshold), when a muscle
      contraction was observed (motor threshold), when stimulation became uncomfortable
      (pain threshold) and when the stimulation became unbearable (pain tolerance).
      Patients also indicated their overall comfort level on a visual analogue scale
      and completed a short verbal interview detailing their experience of the NMES
      treatment. Results indicated that the presence of a metallic implant did not give
      rise to hypersensitivity to NMES. Patients found the application of calf muscle
      NMES comfortable and acceptable as a treatment. We conclude that use of NMES on
      postoperative orthopaedic patients can be safely considered as a DVT prevention
      method.

PMID- 21096914
TI  - Effectiveness of functional electrical stimulation (FES)-robot assisted wrist
      training on persons after stroke.
AB  - A functional electrical stimulation (FES)-robot system controlled by subjects'
      motor intention was developed in our previous study. The effectiveness of the FES
      robot on wrist training was investigated in this work. Five hemiplegic subjects
      with chronic stroke were recruited for an FES-robot assisted wrist training with
      20 sessions. After the training, motor improvements were found in the wrist and
      fingers, represented by significant increase (P < 0.05) in clinical scores of the
      Fugl-Meyer Assessment (FMA), the Action Research Arm Test (ARAT), and the
      Modified Ashworth Score (MAS). Muscle coordination in the upper limb was also
      improved during the training as assessed by electromyography. The increased ARAT
      scores suggested improved upper limb motor functions, especially in the hand and
      fingers, compared to no improvement in previous study with only interactive robot
      assisted wrist training without FES.

PMID- 21096916
TI  - Electrocutaneous stimulation system for Braille reading.
AB  - This work is an assistive technology for people with visual disabilities and aims
      to facilitate access to written information in order to achieve better social
      inclusion and integration into work and educational activities. Two methods of
      electrical stimulation (by current and voltage) of the mechanoreceptors was
      tested to obtain tactile sensations on the fingertip. Current and voltage
      stimulation were tested in a Braille cell and line prototype, respectively. These
      prototypes are evaluated in 33 blind and visually impaired subjects. The result
      of experimentation with both methods showed that electrical stimulation causes
      sensations of touch defined in the fingertip. Better results in the Braille
      characters reading were obtained with current stimulation (85% accuracy). However
      this form of stimulation causes uncomfortable sensations. The latter feeling was
      minimized with the method of voltage stimulation, but with low efficiency (50%
      accuracy) in terms of identification of the characters. We concluded that
      electrical stimulation is a promising method for the development of a simple and
      unexpensive Braille reading system for blind people. We observed that voltage
      stimulation is preferred by the users. However, more experimental tests must be
      carry out in order to find the optimum values of the stimulus parameters and
      increase the accuracy the Braille characters reading.

PMID- 21096917
TI  - Cochlear implant design for better representation of basilar membrane mechanics.
AB  - The performance of cochlear implants (CIs) is limited by the relatively low
      number of electrodes used. While CIs can perform adequately when emulating place
      codes, they cannot be used to convey detailed spatiotemporal codes. This makes it
      difficult to represent complex sounds that depend on the relative timing of
      events over a broad region of the basilar membrane. To address this problem it is
      likely that future implants will increase the number of electrodes. This paper
      presents analysis and results that may be used to decide how many electrodes
      would be suitable, in the context of improving pitch discrimination.

PMID- 21096918
TI  - Non-invasive muscle force assessment apparatus for use in the intensive care
      unit.
AB  - Muscle function assessment is important for diagnosing muscular disorders,
      developing treatment plans, and tracking patient progress over time. The muscle
      force assessment system (MFAS) can provide quantitative results versus the
      traditional qualitative results that are obtained from manual tests. A new MFAS
      was developed for measuring force in the tibialis anterior muscle in response to
      electrical stimulation. The system is small, portable, and can be used in an ICU
      setting. Preliminary experiments were conducted to compare the new system to an
      existing force assessment system. The results demonstrated that the new system is
      repeatable and reliable.

PMID- 21096919
TI  - Surface EMG analysis of tibialis anterior muscle in walking with FES in stroke
      subjects.
AB  - In this work we have examined the effect of functional electrical stimulation
      (FES) in the management of drop foot in stroke subjects with surface
      electromyographic (sEMG) analysis from the tibialis anterior (TA) muscle. Ten
      subjects were assigned to FES therapy combined with conventional stroke
      rehabilitation program 5 days a week, 60 min a day, for 12-weeks in clinical
      settings. Baseline and post-treatment measurements were made for temporal and
      spectral parameters of EMG signals of TA muscle. The evaluation results reported
      an increase in mean-absolute-value (MAV), root-mean-square (RMS) and also
      improved the amplitude and median frequency (MF) of the sEMG power spectrum in
      monitoring the improvement of the tibialis anterior muscle during maximum
      voluntary contractions (MVC). We conclude that walking with FES system combined
      with a conventional rehabilitation program improves the muscle strength in stroke
      survivors.

PMID- 21096920
TI  - H-reflex measurement and a simulation model for interpreting the effect of an
      auxiliary electrical stimulation on FES.
AB  - As reported by some researchers, human responses to Functional Electrical
      Stimulation (FES) are likely to be affected by several factors, such as
      spasticity, muscle fatigue, nerve habituation and so forth. In our previous
      study, it has been shown that, an sub-threshold Auxiliary Stimulation (AS) to the
      Gastrocnemius, with current frequency ranged from 2000 to 6000Hz, could alleviate
      the symptom of spasticity and muscle fatigue caused by the stimulation to the
      Tibialis Anterior, enable comparatively stable and durable function restoration
      assistance. To understand the underlying neuromuscular processes elicited by the
      auxiliary electrical stimulation and its qualitative natures, we have measured
      the Hoffmann-reflex (H-reflex) in human soleus muscle before and after the AS in
      this study,, and proposed a mathematical model which takes into consideration not
      only the efferent but also afferent neural pathways, to interpret the
      effectiveness of the AS. Based on the results from the experiment it can be noted
      that: H(max)/M(max) became lower after AS, AS could reduce the excessive
      excitability of Alpha MNs. The mathematical model of pre-synaptic inhibition
      could help us to understand the underlying neuromuscular processes elicited by
      electrical stimulation and its qualitative nature, and used it to predict the
      states of spinal cord more easily, quickly, and reasonably in clinic experiment
      as a medical evaluation method for the paralyzed humans.

PMID- 21096921
TI  - Estimation of finger postures to control a maniform device for playing a trumpet
      using electromyographic signals with external triggers.
AB  - Electromyographic (EMG) signals have been used to control active prosthetic arms
      for amputees. One of the obstacles in making such prosthetic arms is the timed
      estimation of posture, because EMG signals and muscle movements are not
      necessarily synchronized. We estimated the finger motions for trumpet players by
      using both surface EMG (sEMG) and the timing information using body motion. The
      algorithms consisted of Principal Component Analysis (PCA), and Support Vector
      Machine (SVM). The results showed that applying the timing information using body
      motion increases how precisely the motion of the fingers is estimated.

PMID- 21096922
TI  - Effect of simultaneous vibrations to two tendons on velocity of the induced
      illusory movement.
AB  - A typical prosthetic limb has sensory shortcomings, one of which is lack of
      kinesthesia. Conventional methods to evoke kinesthesia, which would be required
      for a precise control of prosthetic limbs, include tendon vibration and skin
      stretch, but these produce only the sensation of small movements. In this study,
      tendon vibration is extended to evoke sensations of a more rapid movement. A
      stimulation method in which vibration is applied to two tendons is proposed, in
      contrast to most studies in which a single tendon was vibrated. Experimental
      results indicated that vibration applied to both ends of a muscle produces
      sensations of more rapid movement than vibration to just one. However, no
      significant difference in sensation was found between vibrating tendons of
      synergistic muscles and a single tendon.

PMID- 21096923
TI  - Assessment of the assistive performance of an ankle exerciser using
      electromyographic signals.
AB  - This paper presents the design of an admittance-based assistive controller and
      preliminary experimental results for a high performance parallel robot used for
      ankle rehabilitation. The goal of this work was to design a suitable control
      algorithm for diagnosis, training and rehabilitation of the ankle in presence of
      musculoskeletal injuries. An admittance control technique is used to perform
      patient-active exercises with and without motion assistance. Electromyographic
      (EMG) signals are used to evaluate patient's effort during training/exercising.
      The results indicate the great potential of the rehabilitation device as a tool
      to fasten and improve the ankle therapies outcome.

PMID- 21096924
TI  - A variable structure pantograph mechanism for comprehensive upper extremity
      haptic movement training.
AB  - Numerous haptic devices have been developed for neurorehabilitation of upper
      extremities, but their wide-spread use has been largely impeded for reasons of
      complexity and cost. In this paper we describe a variable structure pantograph
      mechanism that produces a versatile rehabilitation robot for movement training of
      the shoulder, elbow, and wrist. The device has three operational modes: ARM,
      REACH and WRIST. The performance of the mechanism, driven by series elastic
      actuators, is similar in all three operational modes while using a single control
      scheme and set of gains. This means a single device with minimal setup changes
      can be used to treat a variety of upper limb impairments following stroke,
      traumatic brain injury, or other direct trauma to the arm.

PMID- 21096925
TI  - Preliminary investigation of test-retest reliability of a robotic assessment for
      Parkinson's disease.
AB  - Several systems have been proposed to objectively quantify the motor signs of
      Parkinson's disease. While validity has been investigated for a subset of these
      systems, test-retest reliability of automated assessments has been more
      neglected. We have created a protocol that uses a robotic system to measure force
      and position as the user performs tracking tasks with and without a simultaneous
      cognitive or motor task. We present preliminary results for test-retest
      reliability with eight individuals with early to moderate PD. Based on this data,
      we identified variables with large, significant correlations between the test and
      retest data. A total of 21 reliable variables were identified with all portions
      of the assessment protocol producing reliable variables.

PMID- 21096926
TI  - Hand spring operated movement enhancer (HandSOME) device for hand rehabilitation
      after stroke.
AB  - Hand rehabilitation after stroke is essential for restoring functional
      independent lifestyles. After stroke, patients often have flexor hypertonia,
      making it difficult to open their hand for functional grasp. The development and
      initial testing of a passive hand rehabilitation device is discussed. The device,
      Hand Spring Operated Movement Enhancer (HandSOME), assists with opening the
      patient's hand using a series of bungee cords that apply extension torques to the
      finger joints that compensate for the flexor hypertonia. This results in
      significant increase in range of motion and functional use when wearing HandSOME,
      even in severely impaired subjects. Device design, calibration, and range of
      motion are described as well as functional and usability testing with stroke
      subjects.

PMID- 21096927
TI  - Tactile communication using a CO(2) flux stimulation for blind or deafblind
      people.
AB  - This paper describes a tactile stimulation system for producing nonvisual image
      patterns to blind or deafblind people. The stimulator yields a CO(2) pulsatile
      flux directed to the user's skin throughout a needle that is coupled to a 2-D
      tactile plotter. The fluxtactile plotter operates with two step motor mounted on
      a wood structure, controlled by a program developed to produce alphanumerical
      characters and geometric figures of different size and speed, which will be used
      to investigate the psychophysical properties of this kind of tactile
      communication. CO(2) is provided by a cylinder that delivers a stable flux, which
      is converted to a pulsatile mode through a high frequency solenoid valve that can
      chop it up to 1 kHz. Also, system temperature is controlled by a Peltier based
      device. Tests on the prototype indicate that the system is a valuable tool to
      investigate the psychophysical properties of the skin in response to stimulation
      by CO(2) jet, allowing a quantitative and qualitative analysis as a function of
      stimulation parameters. With the system developed, it was possible to plot the
      geometric figures proposed: triangles, rectangles and octagons, in different
      sizes and speeds, and verify the control of the frequency of CO(2) jet stimuli.

PMID- 21096928
TI  - Current research of C-Sight visual prosthesis for the blind.
AB  - Electrical stimulation of the optic nerve with penetrating electrode array for
      visual recovery had been proposed by C-Sight group. This paper presents the
      latest progress of various component parts of visual prosthesis, including design
      and testing of neural stimulator, fabrication of multi-channel flexible
      microelectrode array. According to the experiment data, the linearity between
      practical stimulator output and the setting parameters has been validated. The
      temporal properties of EEP evoked by optic nerve stimulation with penetrating
      electrodes will be introduced briefly according to in vivo electrophysiological
      study.

PMID- 21096929
TI  - Discrete cortical responses from multi-site supra-choroidal electrical
      stimulation in the feline retina.
AB  - Exploration into electrical stimulation of the retina has thus far focussed
      primarily upon the development of prostheses targeted at one of two sites of
      intervention - the epi- and sub-retinal surfaces. These two approaches have
      sound, logical merit owing to their proximity to retinal neurons and their
      potential to deliver stimuli via the surviving retinal neural networks
      respectively. There is increasing evidence, however, that electric field effects,
      electrode engineering limitations, and electrode-tissue interactions limit the
      spatial resolution that once was hoped could be elicited from electrical
      stimulation at epi- and sub-retinal sites. An alternative approach has been
      proposed that places a stimulating electrode array within the supra-choroidal
      space - that is, between the sclera and the choroid. Here we investigate whether
      discrete, cortical activity patterns can be elicited via electrical stimulation
      of a feline retina using a custom, 14 channel, silicone rubber and Pt electrode
      array arranged in two hexagons comprising seven electrodes each. Cortical
      responses from Areas 17/18 were acquired using a silicon-based, multi-channel,
      penetrating probe developed at IMTEK, University of Freiburg, within the European
      research project NeuroProbes. Multi-unit spike activity was recorded in synchrony
      with the presentation of electrical stimuli. Results show that distinct cortical
      response patterns could be elicited from each hexagon separated by 1.8 mm (center
      to-center) with a center-to-center electrode spacing within each hexagon of 0.55
      mm. This lends support that higher spatial resolution may also be discerned.

PMID- 21096930
TI  - A CMOS-based multichip flexible retinal stimulator for simultaneous multi-site
      stimulation.
AB  - We developed a novel CMOS-based multichip flexible neural stimulator with on-chip
      stimulation generator. It enables simultaneous multi-site stimulation. We also
      propose a new type of multi-chip retinal stimulator with single electrode / unit
      chip configuration. We successfully performed simultaneous multi-site stimulation
      in an in vivo retinal stimulation experiment using a rabbit.

PMID- 21096931
TI  - Correction for Chinese character patterns formed by simulated irregular phosphene
      map.
AB  - To reduce the unfavorable influence of phosphene array irregularity on the form
      of Chinese character pattern so as to improve recognition accuracy in visual
      prostheses, two correction methods were put forward. One method was to generate
      phosphene closest to the target point in regular arrays using weighted nearest
      neighbor search. The other was to generate phosphene whose center located in the
      region covered by dilated characters. Based on a simulation system, Chinese
      character recognition tests were given to fifteen normally sighted subjects under
      five degrees of array irregularity (0.2, 0.4, 0.6, 0.8, 1.0) without correction.
      The recognition accuracy decreased with the increase of irregularity. When the
      recognition accuracy dropped below 80%, two correction methods were applied and
      their effects were evaluated. With the increase of array irregularity, both
      effects on the accuracy of recognition grew considerably. Comparison between the
      two methods revealed that the former method afforded higher recognition accuracy
      and the latter only applied to phosphene map with serious irregularity.

PMID- 21096932
TI  - Higher-order sliding mode control of leg power in paraplegic FES-cycling.
AB  - In this paper, we propose a robust control methodology based on high order
      sliding mode (HOSM) for control of the leg power in FES-Cycling. A major obstacle
      to the development of control systems for functional electrical stimulation (FES)
      has been the highly non-linear, time-varying properties of neuromusculoskeletal
      systems. A useful and powerful control scheme to deal with the uncertainties,
      nonlinearities, and bounded external disturbances is the sliding mode control
      (SMC). The main drawback of the classical sliding mode is mostly related to the
      so-called chattering which is dangerous for FES applications. To avoid
      chattering, HOSM approaches were proposed. Keeping the main advantages of the
      original approach, at the same time they totally remove the chattering effect and
      provide for even higher accuracy in realization. The results of simulation
      studies and experiments on two paraplegic subjects show the superior performance
      of the leg power control during different conditions of operation using HOSM
      control scheme.

PMID- 21096933
TI  - Vision based interface: an alternative tool for children with cerebral palsy.
AB  - In this paper a new vision based interface (VBI) for children with cerebral palsy
      is presented. The VBI is implemented for the interaction between children and
      computer. The VBI detects and tracks the movement of the hand, foot or head of
      the user. These movements are translated into movements of the cursor on the
      screen of the computer. The evaluation of system user-VBI is based on HAAT model.
      The experimental results show four vase studies of children, when they carried
      out different tasks with the computer.

PMID- 21096934
TI  - Mixed reality rehabilitation for stroke survivors promotes generalized motor
      improvements.
AB  - This paper presents results from a clinical study of stroke survivors using an
      adaptive, mixed-reality rehabilitation (AMRR) system for reach and grasp therapy.
      The AMRR therapy provides audio and visual feedback on the therapy task, based on
      detailed motion capture, that places the movement in an abstract, artistic
      context. This type of environment promotes the generalizability of movement
      strategies, which is shown through kinematic improvements on an untrained
      reaching task and higher clinical scale scores, in addition to kinematic
      improvements in the trained task.

PMID- 21096935
TI  - Enhancement of bend sensor properties as applied in a glove for use in
      neurorehabilitation settings.
AB  - Following hand function impairment caused by a neurological disorder, the
      functional level of the upper extremities has to be assessed in the clinical and
      rehabilitation settings. Current hand function evaluation tests are somewhat
      imprecise. Instrumented gloves allow finger motion monitoring during the
      performance of skilled tasks, such as grasping objects. As a result, they provide
      an objective tool for evaluating slight changes in the fine motor skills of the
      hand. Numerous gloves are based on resistive bend sensors, given that this is an
      easy to handle, low-cost, and reliable sensing element. When bending is not
      applied homogeneously along such a sensor, as is the case with finger-joint
      bending, its output response varies with the sensor's longitudinal position. Our
      goal is to determine the optimal sensor position with respect to the finger-joint
      in order to enhance the resolution of the sensors embedded in a glove. The
      validity of the integrated sensors is evaluated and the accuracy values are
      given.

PMID- 21096936
TI  - Dynamic range considerations when designing PC sound card based audiometric
      systems to test human hearing.
AB  - An investigation into maximizing the dynamic range of a PC sound card based
      audiometric test system is presented. Two principle sound paths are
      characterized: a) the analog line input, and, b) internal waveform conversion
      from digital formats into analog signals. Each signal path's electrical
      performance and overall dynamic range is measured using audio harmonic distortion
      analysis and frequency spectrum analysis tools. Recommendations are made for
      proper combinations of signal amplitude and mixer attenuation settings to
      maximize overall system dynamic range. This work could be useful for scientists
      using PC sound card based systems for psycho-acoustic testing purposes or for
      those using similar systems attempting to test the full range of human hearing.

PMID- 21096937
TI  - Perturbation-based measurement of real and imaginary parts of human arm's
      mechanical impedance.
AB  - Mechanical impedance is a complex number and a system's property. Impedance of
      human arm is the control variable when the central nervous system coordinates a
      motion. This research proposes a new method for measuring the mechanical
      impedance as a complex number. Impedance is measured at the hand point while
      sinusoidal perturbation is applied. That helps extracting the real and imaginary
      part of the impedance. Simulations reveal how spring, mass, and damper contribute
      to the mechanical impedance. Despite the simulation results, our experiment shows
      that damping which is the real part of impedance is not frequency independent and
      imaginary part of mechanical impedance decreased with increasing frequency that
      in turn suggests the stiffness is increasing.

PMID- 21096938
TI  - Visual error augmentation enhances learning in three dimensions.
AB  - Recent human motor learning and neuro-rehabilitation experiments have identified
      the benefits of assisting the learning process by artificially enhancing the
      errors one might experience. A yet untested question is just how far the nervous
      system will trust such treatments, especially in transformations with very large
      sensorimotor discrepancies. Our study asked 10 healthy subjects to perform
      targeted reaching in a virtual reality environment, where the transformation of
      the hand position matrix was a complete reversal - rotated 180 degrees about an
      arbitrary axis (hence 2 of the 3 coordinates are reversed). Our data show that
      after 500 practice trials, subject who received 2x Error Augmentation (EA) were
      able to reach their desired target 0.4 seconds more quickly and with a Maximum
      Perpendicular Trajectory deviation of 0.9 cm less, when compared to the control
      group. Furthermore, the manner in which subjects practiced was influenced by the
      error augmentation, resulting in more continuous motions for this group. These
      data further support that this type of enhancement, as well as possibly other
      distorted reality methods, may promote more complete adaptation/learning when
      compared to regular training.

PMID- 21096940
TI  - Dependability: a challenge for electrical medical implants.
AB  - Functional Electrical Stimulation (FES) is an attractive solution to restore some
      lost or failing physiological functions. Obviously, the FES system may be
      hazardous for patient and the reliability and dependability of the system must be
      maximal. Unfortunately, the present context, where the associated systems are
      more and more complex and their development needs very cross-disciplinary
      experts, is not favorable to safety. Moreover, the direct adaptation of the
      existing dependability techniques from domains such as space or automotive is not
      suitable. Firstly, this paper proposes a strategy for risk management at system
      level for FES medical implant. The idea is to give a uniform framework where all
      possible hazards are highlighted and associated consequences are minimized. Then,
      the paper focuses on critical parts of the FES system: analog micro-circuit which
      generates the electrical signal to electrode. As this micro-circuit is the
      closest to the human tissue, any failure might involve very critical consequences
      for the patient. We propose a concurrent top-down and bottom-up approach where
      the critical elements are highlighted and an extended risk analysis is performed.

PMID- 21096939
TI  - Restoration of useful vision up to letter recognition capabilities using
      subretinal microphotodiodes.
AB  - Our group has developed a subretinal microphotodiode array for restoration of
      vision. In a clinical pilot study the array has been implanted in 11 patients
      suffering from photoreceptor degenerations. Here we present promising results
      from some of those patients where the retinal tissue above the chip was
      functional and the implant fulfilled its expected function. A spatial resolution
      of approximately 0.3 cycles/degree could be achieved with fine stripe patterns.
      In one subject where the implant had been placed directly under the macular
      region of the retina a visual acuity of 20/1000 could be measured. Artificially
      restored visual acuity of this quality has not been reported previously. Finally,
      we present images illustrating an approximation of how the visual perceptions
      might have appeared to the subjects, based on a mathematical model and patient
      reports.

PMID- 21096941
TI  - Engineering evaluation of the energy-storing orthosis FES gait system.
AB  - A system to restore walking in the vicinity of a wheelchair for people with
      paraplegia resulting from spinal cord injury is under development. The approach
      combines single channel surface electrical stimulation with an orthosis. The
      orthosis is spring loaded and contains a pneumatic system that stores energy
      during knee extension caused by quadriceps stimulation and transfers it to hip
      joint for hip extension. A laboratory version of the prototype of the gait system
      has been fabricated and engineering bench tests were performed. The paper
      presents the design of the wearable prototype and results of bench testing.

PMID- 21096942
TI  - Symmetric multi-scale image registration.
AB  - It is known that the transformations estimated in most of the non-rigid image
      registration methods are not invertible. This means that the transformation is
      not one-to-one and also it defines the deformation only in one direction making
      the registration methods become inconsistent. The symmetric image registration
      method is a solution to constrain the estimated transformation to become more
      consistent. This technique promotes the quality of registration significantly. In
      this paper we present symmetric non-rigid image registration method using multi
      scale approach, defining the registration progressively in four different image
      scales which used result of the previous level as the initial condition for the
      next level. Our proposed algorithm uses a symmetric cost function which includes
      forward and backward transformations. Regularization term is used for both
      forward and reverse deformation fields to control the spatial behavior of the
      transformation. The results show improving the image similarity and consistency
      compared to asymmetric methods.

PMID- 21096943
TI  - Registering a non-rigid multi-sensor ensemble of images.
AB  - The majority of image registration methods deal with registering only two images
      at a time. Recently, a clustering method that concurrently registers more than
      two multi-sensor images was proposed, dubbed ensemble clustering. In this paper,
      we apply the ensemble clustering method to a deformable registration scenario for
      the first time. Non-rigid deformation is implemented by a free-form deformation
      model based on B-splines with a regularization term. However, the increased
      degrees of freedom in the transformations caused the Newton-type optimization
      process to become ill-conditioned. This made the registration process unstable.
      We solved this problem by using the matrix approximation afforded by the singular
      value decomposition (SVD). Experiments show that the method is successfully
      applied to non-rigid multi-sensor ensembles and overall yields better
      registration results than methods that register only two images at a time.

PMID- 21096944
TI  - Statistical shape modeling of pathological scoliotic vertebrae: A comparative
      analysis.
AB  - Statistical shape models (SSMs) have been used widely as a basis for segmenting
      and interpreting complex anatomical structures. The robustness of these models
      are sensitive to the registration procedures, i.e., establishment of a dense
      correspondence across a training data set. In this work, two SSMs based on the
      same training data set of scoliotic vertebrae, and registration procedures were
      compared. The first model was constructed based on the original binary masks
      without applying any image pre- and post-processing, and the second was obtained
      by means of a feature preserving smoothing method applied to the original
      training data set, followed by a standard rasterization algorithm. The accuracies
      of the correspondences were assessed quantitatively by means of the maximum of
      the mean minimum distance (MMMD) and Hausdorf distance (H(D)). Anatomical
      validity of the models were quantified by means of three different criteria,
      i.e., compactness, specificity, and model generalization ability. The objective
      of this study was to compare quasi-identical models based on standard metrics.
      Preliminary results suggest that the MMMD distance and eigenvalues are not
      sensitive metrics for evaluating the performance and robustness of SSMs.

PMID- 21096945
TI  - Multiple registration of coronal and sagittal MR temporal image sequences based
      on Hough transform.
AB  - This work discusses the use of breathing patterns present in time sequences of MR
      images in the temporal registration of coronal and sagittal images. The
      registration is done without the use of any triggering information and any
      special gas to enhance the contrast. The temporal sequences of images are
      acquired in free breathing. As coronal and sagittal sequences of images are
      orthogonal to each other, their intersection corresponds to a segment in the
      three dimensional space. The registration happens by analyzing this intersection
      segment that is determined by a coronal-sagittal mapping. A time sequence of this
      intersection segment can be stacked, defining a two dimension spatio-temporal
      (2DST) image. It is assumed that the diaphragmatic movement is the principal
      movement and all the lungs structures do move almost synchronously. The
      synchronization was realized through a pattern named respiratory function. A
      Hough transform algorithm, using the respiratory function as input, searches for
      synchronized movements with the respiratory function. Finally, the composition of
      coronal and sagittal images that are in the same breathing phase is made by
      comparison of diaphragmatic respiratory patterns. Several results and conclusions
      are shown.

PMID- 21096946
TI  - A hybrid multimodal non-rigid registration of MR images based on diffeomorphic
      demons.
AB  - In this paper we present a novel hybrid approach for multimodal medical image
      registration based on diffeomorphic demons. Diffeomorphic demons have proven to
      be a robust and efficient way for intensity-based image registration. A very
      recent extension even allows to use mutual information (MI) as a similarity
      measure to registration multimodal images. However, due to the intensity
      correspondence uncertainty existing in some anatomical parts, it is difficult for
      a purely intensity-based algorithm to solve the registration problem. Therefore,
      we propose to combine the resulting transformations from both intensity-based and
      landmark-based methods for multimodal non-rigid registration based on
      diffeomorphic demons. Several experiments on different types of MR images were
      conducted, for which we show that a better anatomical correspondence between the
      images can be obtained using the hybrid approach than using either intensity
      information or landmarks alone.

PMID- 21096947
TI  - Spatio-temporal registration of cardiac perfusion MRI exams using high
      dimensional mutual information.
AB  - Compensating for cardio-thoracic motion artifacts in contrast-enhanced cardiac
      perfusion MRI (p-MRI) sequences is a key issue for the quantitative assessment of
      myocardial iscaemia. The classical paradigm consists of registering each sequence
      frame on some reference using an intensity-based matching criterion. In this
      paper, we present a novel unsupervised method for the groupwise registration of
      cardiac p-MRI exams based on mutual information between high-dimensional feature
      distributions. Specifically, local contrast enhancement curves are used as a
      dense set of spatio-temporal features, and statistically matched to a target
      feature distribution derived from a registered reference template. Using
      consistent kth nearest neighbors entropy estimators further enables the
      variational optimization of the model over finite- and infinite-dimensional
      transform spaces. Experiments on simulated and natural datasets demonstrate its
      accuracy and relevance for the reliable assessment of regional perfusion.

PMID- 21096948
TI  - EEG complexity during sleep: on the effect of micro and macro sleep structure.
AB  - This work investigates the relation between EEG complexity measures, in
      particular Fractal Dimension and Sample Entropy, and sleep structure, in terms of
      both macrostructure, i.e. sleep stages, and microstructure, i.e. phase A
      activation of CAP sleep. Activation phases are compared with the non-activation
      periods of non-REM sleep. The study suggests that complexity features can serve
      as consistent descriptors of sleep dynamics and can potentially assist in the
      classification of sleep stages.

PMID- 21096949
TI  - Coherence in depth electrodes during induction of deep anesthesia.
AB  - Our aim was to explore time-varying coherence values versus spacing and
      referencing of electrode contacts in thalamic level from human encephalographic
      (EEG) data. Data has been acquired during induction of propofol anesthesia until
      burst-suppression level in scalp EEG. Results are shown from coherence analysis
      applied to EEG signals from selected depth electrode contacts pair-wise of three
      subjects. Alpha coherence is the most prominent behavior in all channel pairs. It
      is persistent throughout the time period followed and in coherence calculated
      between bipolar derivations in depth electrodes.

PMID- 21096950
TI  - Interpretation of the approximate entropy using fixed tolerance values as a
      measure of amplitude variations in biomedical signals.
AB  - A new method for the quantification of amplitude variations in biomedical signals
      through moving approximate entropy is presented. Unlike the usual method to
      calculate the approximate entropy (ApEn), in which the tolerance value (r) varies
      based on the standard deviation of each moving window, in this work ApEn has been
      computed using a fixed value of r. We called this method, moving approximate
      entropy with fixed tolerance values: ApEn(f). The obtained results indicate that
      ApEn(f) allows determining amplitude variations in biomedical data series. These
      amplitude variations are better determined when intermediate values of tolerance
      are used. The study performed in diaphragmatic mechanomyographic signals shows
      that the ApEn(f) curve is more correlated with the respiratory effort than the
      standard RMS amplitude parameter. Furthermore, it has been observed that the
      ApEn(f) parameter is less affected by the existence of impulsive, sinusoidal,
      constant and Gaussian noises in comparison with the RMS amplitude parameter.

PMID- 21096951
TI  - Assessment of the depth of anesthesia based on symbolic dynamics of the EEG.
AB  - Methodologies based on symbolic dynamics have successfully demonstrated to
      reflect the nonlinear behavior of biological signals. In the present study,
      symbolic dynamics was applied to the electroencephalogram (EEG) in order to
      describe the level of depth of anesthesia. The EEG was transformed to symbol
      sequences. Words of three symbols were built from this symbolic series. The
      results obtained from the EEGs of 36 patients undergoing anesthesia showed that
      the probabilities of the word types were able to reflect the depth of anesthesia
      in a similar way to the auditory evoked potential index AAI, a commercial index.

PMID- 21096952
TI  - Energy estimation of treadmill walking using on-body accelerometers and
      gyroscopes.
AB  - Walking is the most common activity among people who are physically active.
      Standard practice physical activity characterization from body-mounted inertial
      sensors uses accelerometer-generated counts. There are two problems with this -
      imprecison (due to usage of proprietary counts) and incompleteness (due to
      incomplete description of motion). We address both these problems by directly
      predicting energy expenditure during steady-state treadmill walking from a hip
      mounted inertial sensor comprised of a tri-axial accelerometer and a tri-axial
      gyroscope. We use Bayesian Linear Regression to predict energy expenditure based
      on modelling joint probabilities of streaming data. The prediction is
      significantly better with data from a 6 axis sensor as compared with streaming
      data from only 2 linear accelerations as is common in current practice. We also
      show how counts from a commercially available accelerometer can be reproduced
      from raw streaming acceleration data (up to a linear transformation) with high
      correlation (.9787 +/- .0089 for the X-axis and .9141 +/- .0460 for the Y-axis
      acceleration streams). The paper emphasizes the role of probabilistic techniques
      in conjunction with joint modeling of tri-axial accelerations and rotational
      rates to improve energy expenditure prediction for steady-state treadmill
      walking.

PMID- 21096953
TI  - Rectus abdominis electromyography and MechanoMyoGraphy comparison for the
      detection of cough.
AB  - We recently developed a novel active implant for the treatment of severe stress
      urinary incontinence. This innovative medical device has been developed with the
      main purpose of reducing the mean urethral occlusive pressure of the current
      prosthesis. This goal is achieved by detecting circumstances implying either high
      or low intra-abdominal pressures by a single 3-axis accelerometer. In fact,
      posture and activity of the patient are monitored in real time. We investigated
      in this study the possibility of detecting cough events (one of the main causes
      of urine loss in incontinent patient) by MechanoMyoGraphy (MMG) of the Rectus
      Abdominis (RA) using the same accelerometer. We compared MMG signal detection
      characteristics (burst onset times and RMS values) to the method of reference,
      the ElectroMyoGraphy (EMG). It is shown that detection of cough effort by MMG
      presents lower performances, mostly in terms of cough anticipation, than EMG
      detection. However, MMG still remains a good option for an implantable system
      comparing to implantable EMG disadvantages.

PMID- 21096954
TI  - Microfluidic based contactless dielectrophoretic device: Modeling and analysis.
AB  - While there have been many attempts at patterning cells onto substrates, a
      reliable method for trapping cell clusters and forming cell arrays in a
      predefined geometry remains to be demonstrated. We intend to develop a
      multielectrode array platform to initially trap cells via dielectrophoresis (DEP)
      and to later measure their electrical activity. As a first step toward that
      objective, here we present an interdigitated microfabricated comb structure. We
      designed an optimal insulation layer via finite element modeling for maximum
      dielectrophoretic field strength in solution and minimal cell damage. The
      microfabricated structure was combined with a microfluidic channel to vertically
      constrain cell position. With the objective of capturing cells onto the
      substrate, we here show that there is an optimal thickness of dielectric which
      limits electrolysis in solution and still allows for sufficient dielectrophoretic
      force on the cells to pull them onto the surface.

PMID- 21096955
TI  - Vulnerability for reentry in a three dimensional model of human atria: a
      simulation study.
AB  - Atrial tachycardias are the most common cardiac arrhythmias in clinical practice,
      which induce changes in atrial properties that help to perpetuate them. These
      changes are called "atrial remodeling". Recent studies have shown that rapid
      ectopic activity principally on the pulmonary veins can trigger reentrant
      mechanisms and lead to atrial tachycardias. However, the influences of ectopic
      foci location, the number of ectopic beats and its frequency on the likelihood of
      triggering reentries are not well known. In this work the effects of electrical
      remodeling were incorporated in an atrial cell model and integrated in a three
      dimensional model of human atria, to develop a study of vulnerability for
      reentries. To carry out the study, an ectopic beat and a burst of six ectopic
      beats at two different frequencies were applied in six different locations in the
      atria. The results show greater vulnerability in the left pulmonary veins when we
      applied a single ectopic beat. When we increase the number of ectopic beats to
      six, a greater width of the vulnerable window was observed when ectopic focus
      frequency was high. The location, the number of ectopic beats and their frequency
      affect the vulnerability for reentry.

PMID- 21096956
TI  - Limitations of the homogenized cardiac Monodomain model for the case of low gap
      junctional coupling.
AB  - The cardiac Monodomain model is a mathematical model extensively used in studies
      of propagation of bioelectric wavefronts in the heart. To be able to use the
      model for complex and large cardiac simulations, such as the case of whole heart
      and 3D simulations, some parameters of the model that are known to
      physiologically vary in space, such as the intracellular conductivity, are
      traditionally kept constant at effective values. These effective values can be
      obtained via a mathematical procedure called homogenization. In this work we
      revisit the classical homogenized monodomain formulation to evaluate its ability
      to reproduce the situation of low gap junctional coupling. This situation arises
      in many pathological conditions such as during ischemia. Our numerical results
      suggest some limitations of the homogenized cardiac Monodomain model under these
      conditions in terms of computed conduction velocity and Action Potential
      waverforms.

PMID- 21096957
TI  - Non lineal respiratory systems mechanics simulation of acute respiratory distress
      syndrome during mechanical ventilation.
AB  - Model and simulation of biological systems help to better understand these
      systems. In ICUs patients often reach a complex situation where supportive
      maneuvers require special expertise. Among them, mechanical ventilation in
      patients suffering from acuter respiratory distress syndrome (ARDS) is specially
      challenging. This work presents a model which can be simulated and use to help in
      training of physicians and respiratory therapists to analyze the respiratory
      mechanics in this kind of patients. We validated the model in 2 ARDS patients.

PMID- 21096958
TI  - Is Normal Pressure Hydrocephalus more than a mechanical disruption to CSF flow?
AB  - This work proposes a new theoretical framework for the water transport in the
      cerebral environment. The approach is based on Multiple-Network Poroelastic
      Theory (MPET) and is a natural extension of poroelasticity, a well reported
      technique applied to cerebrospinal fluid (CSF) transport. MPET accounts for the
      transport of CSF and blood simultaneously, as they permeate and deform the
      cerebral tissue. To demonstrate the strength of this approach, MPET is applied to
      one of the most paradoxical and non-intuitive cerebral pathologies, Normal
      Pressure Hydrocephalus (NPH). It is shown, for the first time, that clinically
      relevant ventricular deformations can be observed in the case of totally
      unobstructed, patient-specific aqueducts. Cerebral diseases are recognised as
      pivotal in healthcare; they relate to a whole host of unmet clinical needs. We
      are convinced that basic understanding of fluid transport, as provided by a
      validated MPET model, is the most promising way to address these needs
      meaningfully, in a clinical setting.

PMID- 21096959
TI  - A reduced order finite element algorithm for surgical simulation.
AB  - We present a reduced order finite element (FE) algorithm suitable for real-time
      nonlinear simulation of soft tissues. A dynamic FE formulation with explicit time
      integration is employed. We demonstrate significant computation acceleration by
      performing the time integration in a low-dimensional generalised basis, generated
      from a set of a priori training simulations. The key mechanism for the
      acceleration is the large increase in integration time step afforded by this
      means. Futhermore, we present a simple procedure for imposing inhomogeneous
      essential boundary conditions, thus overcoming one of the principal deficiencies
      of such approaches. The algorithm is described and demonstrated using an example
      neurosurgical simulation. The computation acceleration and errors introduced are
      examined.

PMID- 21096960
TI  - An anatomically realistic 3d model of atrial propagation based on experimentally
      recorded action potentials.
AB  - A three-dimensional anatomically and electro-physiologically realistic model of
      atrial propagation is developed utilizing generic cardiac ionic models fitted to
      experimentally recorded action potentials (APs). The atrial geometry incorporated
      realistic wall thickness and twelve anatomical structures, including the sino
      atrial node (SAN), pulmonary veins, interatrial septum, Bachmann's bundle and
      coronary sinus as interatrial conduction pathways. The SAN was further subdivided
      into central and peripheral regions, characterized by different ionic parameters.
      These parameters were obtained by optimizing ionic models to fit spontaneous APs
      recorded intracellularly from intact rabbit in vitro sino-atrial tissue
      preparations. The SAN region in the 3D model was able to initiate spontaneous
      rhythmic APs and excite the surrounding atrium. The pattern of atrial activation
      was similar to that observed in humans. The use of model optimization allows
      direct incorporation of experimental data into anatomically realistic geometries
      and is a step towards developing patient-specific models for the treatment of
      atrial arrhythmias.

PMID- 21096961
TI  - Visualization and clustering of sleep states in a frequency domain feature space.
AB  - Sleep studies assess the recurrent manifestation of stereotype configurations of
      relevant biosignals. These configurations are known as states (Wake, REM sleep
      and NonREM sleep) and stages (N1-N3 within NREM sleep). These two fundamental
      descriptive domains, time course and variable configuration, can be readily
      rendered available through improved visualization techniques. Time course is
      summarized by EEG spectrograms, instantaneous frequency analysis of cardio
      respiratory signals and other sleep dependent variables. State and stage
      configurations can be further evidenced as clusters in 2D or 3D spaces whose axis
      are sleep-relevant extracted variables. The latter techniques also allows for
      visualization of transition process as pathways from one cluster to another.

PMID- 21096962
TI  - The natural history of the sleep and respiratory engineering track at EMBC 1988
      to 2010.
AB  - Sleep science and respiratory engineering as medical subspecialties and research
      areas grew up side-by-side with biomedical engineering. The formation of EMBS in
      the 1950's and the discovery of REM sleep in the 1950's led to parallel
      development and interaction of sleep and biomedical engineering in diagnostics
      and therapeutics.

PMID- 21096964
TI  - The educational value of teaching biomedical engineering history.
AB  - It has been previously argued that science and engineering undergraduate students
      can benefit greatly from learning the history of their discipline. In order to
      successfully enhance learning by introducing history into undergraduate
      curriculum, it would be desirable to assess what the current educational uses of
      history are and to understand the needs and perceptions of teachers.
      Nevertheless, to our knowledge no quantitative study of the role of the history
      of science, engineering, and technology in the classroom has been so far
      conducted. In this paper we present the design of a survey aimed at assessing the
      current perception of teachers towards using the history of biomedical
      engineering (HBME) to enhance learning. This survey was part of a broader project
      originally led by the EMBS History Committee aimed at evaluating the educational
      value of the HBME, both for future biomedical engineers and for the broader
      public. The main goals of the survey are (1) to find out the current uses of the
      HBME in the classroom, and (2) to identify possible obstacles to expanding the
      HBME in the classroom.

PMID- 21096963
TI  - Lab-on-a-chip for the isolation and characterization of circulating tumor cells.
AB  - A smart miniaturized system is being proposed for the isolation and
      characterization of circulating tumor cells (CTCs) directly from blood. Different
      microfluidic modules have been designed for cell enrichment and -counting,
      multiplex mRNA amplification as well as DNA detection. With the different modules
      at hand, future effort will focus on the integration of the modules in a fully
      automated, single platform.

PMID- 21096965
TI  - From the foundation act to the corporate culture of a BME teaching institute.
AB  - This paper describes the concept and application of the organizational culture of
      a BME teaching institute, based on the specificity of biomedical engineering.
      Selected values and behavioral patterns typical for this profession were endorsed
      to reinforce the mutual cooperation and understanding of students, university
      staff and employers as partners in the educational process. Besides of building a
      professional pride and reputation of the teaching institute, the corporate
      culture is proved to be useful in imposing of the attitudes required in future
      career of the biomedical engineer as a partner of a medic in his efforts aimed at
      the wellness and safety of the patient. Five years since the foundation of the
      Multidisciplinary School of engineering In Biomedicine we still do not have a
      quantitative measure of the educational outcome quality, nevertheless the
      presented idea may be very useful and worth sharing with all BME educators.

PMID- 21096966
TI  - BME education program and research activities at the National Autonomous
      University of Mexico (UNAM).
AB  - Biomedical engineering at the Universidad Nacional Autonoma de Mexico (UNAM -
      National Autonomous University of Mexico) has been developing slowly compared to
      other local universities. A BME-closing module was established as an elective one
      for the bachelors of electronic and computer engineering degrees and it has been
      offered recently. This approach enables the students to apply the principles of
      physics and engineering in a biomedical context. The popularity of the BME
      closing module is growing and more students are opting for this module. This
      paper presents the BME activities at the UNAM and the experience of the elective
      module.

PMID- 21096967
TI  - A GPU-based calculation using the three-dimensional FDTD method for
      electromagnetic field analysis.
AB  - Numerical simulations with the numerical human model using the finite-difference
      time domain (FDTD) method have recently been performed frequently in a number of
      fields in biomedical engineering. However, the FDTD calculation runs too slowly.
      We focus, therefore, on general purpose programming on the graphics processing
      unit (GPGPU). The three-dimensional FDTD method was implemented on the GPU using
      Compute Unified Device Architecture (CUDA). In this study, we used the NVIDIA
      Tesla C1060 as a GPGPU board. The performance of the GPU is evaluated in
      comparison with the performance of a conventional CPU and a vector supercomputer.
      The results indicate that three-dimensional FDTD calculations using a GPU can
      significantly reduce run time in comparison with that using a conventional CPU,
      even a native GPU implementation of the three-dimensional FDTD method, while the
      GPU/CPU speed ratio varies with the calculation domain and thread block size.

PMID- 21096968
TI  - INSIGHT: RFID and Bluetooth enabled automated space for the blind and visually
      impaired.
AB  - In this paper we introduce INSIGHT, an indoor location tracking and navigation
      system to help the blind and visually impaired to easily navigate to their chosen
      destination in a public building. INSIGHT makes use of RFID and Bluetooth
      technology deployed within the building to locate and track the users. The PDA
      based user device interacts with INSIGHT server and provides the user navigation
      instructions in an audio form. The proposed system provides multi-resolution
      localization of the users, facilitating the provision of accurate navigation
      instructions when the user is in the vicinity of the RFID tags as well as
      accommodating a PANIC button which provides navigation instructions when the user
      is anywhere in the building. Moreover, the system will continuously monitor the
      zone in which the user walks. This will enable the system to identify if the user
      is located in the wrong zone of the building which may not lead to the desired
      destination.

PMID- 21096969
TI  - Development of automatic operated blood sampling system for portable type Self
      Monitoring Blood Glucose device.
AB  - In this study, a new portable type Self-Monitoring Blood Glucose (SMBG) device,
      which is driven automatically from the blood sampling to the blood glucose
      measurement, is developed to establish the point-of-care technology in the
      ubiquitous medical care. It aims to overcome human errors due to the complicated
      manual operation of commercial SMBG devices. In this study, I mainly discuss the
      development of automatic operated blood sampling system. This system consists of
      Three Dimensional Blood Bessel Search (3D BVS) unit employing Near-Infrared Light
      (NIR) imaging and the stereo method, and automatic blood collection and
      transportation system. A prototype of the blood sampling system was examined its
      performance and confirmed the high accuracy in 1) blood vessel search, 2)
      punctuation and blood suction, and 3) transportation.

PMID- 21096970
TI  - Classifying human motion quality for knee osteoarthritis using accelerometers.
AB  - In this paper, we describe methods for assessment of exercise quality using body
      worn tri-axial accelerometers. We assess exercise quality by building a
      classifier that labels incorrect exercises. The incorrect performances are
      divided into a number of classes of errors as defined by a physical therapist. We
      focus on exercises commonly prescribed for knee osteoarthritis: standing
      hamstring curl, reverse hip abduction, and lying straight leg raise. The methods
      presented here will form the basis for an at-home rehabilitation device that will
      recognize errors in patient exercise performance, provide appropriate feedback on
      the performance, and motivate the patient to continue the prescribed regimen.

PMID- 21096971
TI  - Intelligent medicine case system with distributed RFID readers.
AB  - In Japan, the number of elderly recipients who take medicines regularly has been
      increasing due to population aging. Since they have many risks of incorrect
      medication, we have developed the intelligent medicine case system (iMec System)
      for assisting their caretakers in medication monitoring. The system confirms the
      type, quantity and timing of medication every time a recipient picks medicines
      up. And then, the system notifies the caretakers about the adequacy of the type,
      quantity, and timing. Since the way of medication is also specified on
      prescription by their doctors, we have strengthened the system so that it
      confirms the way of medication when the recipient picks medicines up. For
      realizing the function, we placed RFID readers in the iMec and the recipient's
      house. The readers measure the movement of objects such as medicines, foods,
      drinks, dishes, utensils. By using the information, the iMec could evaluate the
      adequacy about how to take medicines. We confirmed that the new system was able
      to recognize foods, drinks and utensils by experiments. In this paper, we propose
      an adequacy evaluation method by applying fuzzy inference.

PMID- 21096972
TI  - A receiver diversity technique for ensuring high reliability of wireless vital
      data gathering in hospital rooms.
AB  - Sensing and wireless technologies have made remarkable advance recently, so
      wireless vital sensors for medical use, which are light-weight but accurate, have
      been commercially available. However, because of the low reliability of the
      wireless data transmission, sensed vital data are often lost in the wireless
      channel and this is a fatal drawback of the devices for continuous monitoring of
      patients in hospitals. This paper investigates the effect of using multiple
      receivers (receiver diversity technique) on the improvement of data loss rate for
      wireless vital data gathering. Experiments with a wireless vital sensor in
      hospital rooms reveal that putting receivers to higher positions such as ceiling
      is advantageous and the use of three receivers can sufficiently improve the data
      loss rate as compared with the use of a single receiver.

PMID- 21096973
TI  - RFID in healthcare environment: electromagnetic compatibility regulatory issues.
AB  - Several wireless technology applications (RFID, WiFi, GSM, GPRS) have been
      developed to improve patient care, reaching a significant success and diffusion
      in healthcare. Given the potential development of such a technology, care must be
      paid on the potential risks deriving from the use of wireless device in
      healthcare, among which one of the most important is the electromagnetic
      interference with medical devices. The analysis of the regulatory issues
      concerning the electromagnetic compatibility of medical devices is essential to
      evaluate if and how the application of the current standards allows an effective
      control of the possible risks associated to the electromagnetic interference on
      medical devices.

PMID- 21096974
TI  - Design of packet erasure mitigation technique using a digital fountain code for
      wearable wireless body area networks.
AB  - This paper presents a digital fountain code as a design criterion in order to
      mitigate packet erasure in wireless wearable body area networks (WBANs). First,
      we measure its radio propagation around the human body between two antennas
      attached to participants, and then analyze the measurement results from the
      standpoint of occurrence ratio of packet erasure. Then, we evaluate the
      application of digital fountain code into such WBANs where a rateless code is
      introduced as such code in order to provide a design criterion for the code.

PMID- 21096975
TI  - Performance analysis of a proposed tightly-coupled medical instrument network
      based on CAN protocol.
AB  - Advances in medical devices and health care has been phenomenal during the recent
      years. Although medical device manufacturers have been improving their
      instruments, network connection of these instruments still rely on proprietary
      technologies. Even if the interface has been provided by the manufacturer (e.g.,
      RS-232, USB, or Ethernet coupled with a proprietary API), there is no widely
      accepted uniform data model to access data of various bedside instruments. There
      is a need for a common standard which allows for internetworking with the medical
      devices from different manufacturers. ISO/IEEE 11073 (X73) is a standard
      attempting to unify the interfaces of all medical devices. X73 defines a client
      access mechanism that would be implemented into the communication controllers
      (residing between an instrument and the network) in order to access/network
      patient data. On the other hand, MediCANTM technology suite has been demonstrated
      with various medical instruments to achieve interfacing and networking with a
      similar goal in its open standardization approach. However, it provides a more
      generic definition for medical data to achieve flexibility for networking and
      client access mechanisms. The instruments are in turn becoming more
      sophisticated; however, the operation of an instrument is still expected to be
      locally done by authorized medical personnel. Unfortunately, each medical
      instrument has its unique proprietary API (application programming interface - if
      any) to provide automated and electronic access to monitoring data. Integration
      of these APIs requires an agreement with the manufacturers towards realization of
      interoperable health care networking. As long as the interoperability of
      instruments with a network is not possible, ubiquitous access to patient status
      is limited only to manual entry based systems. This paper demonstrates an attempt
      to realize an interoperable medical instrument interface for networking using
      MediCAN technology suite as an open standard.

PMID- 21096976
TI  - Development of a Zigbee platform for bioinstrumentation.
AB  - This paper presents the development of a network platform which allows connecting
      multiple individual wireless devices for transmitting bioelectrics and
      biomechanics signals for application in a hospital network, or continuous
      monitoring in a patient's diary life. The Zigbee platform development proposal
      was made in three stages: 1) Hardware development, including the construction of
      a prototype network node and the integration of sensors, (2) Evaluation, in order
      to define the specifications of each node and scope of communication and (3) The
      Zigbee Network Implementation for bioinstrumentation based on ZigBee Health Care
      public application profile (ZHC). Finally, this work presents the experimental
      results based on measurements of Lost Packets and LQI (Link Quality Indicator),
      and the Zigbee Platform configuration for Bioinstrumentation in operation.

PMID- 21096977
TI  - Faux-floor development system for personnel detection using signal scavenging
      sensors.
AB  - Motivated by the need to detect motion in elderly people, resulting in falls, we
      have developed a low cost sensor system using aluminum foil as the sensor of
      static electricity and electromagnetic energy. But to make this a system we need
      to amplify the data and use it by displaying the motion or activity of a person.
      We constructed a faux floor development board to provide an initial pilot test of
      the idea of using stray electric energy, or as we call it signal scavenging. The
      foils are placed on the faux floor (in this case a 1 m X 1 m wooden surface)
      allowing foil excitation from the motion of a test subject. The faux floor is a
      useful tool allowing testing of different foils, analog and digital electronics
      circuits and different carpeting. Importantly, even though the system supported a
      small number of foil sensors its performance characteristics clearly show the
      excellent detection capability of the system. Testing the timing characteristics
      resulted in reading the 4 sensors in 3.11 msec, indicating that for even a large
      system of a few hundred sensors we can poll the foils in sufficient time to
      detect the motion of people. Our data show true positive rates of 98% and false
      positive and false negative rates of 2%, a high detection rate. Using the
      development board has provided much helpful information on the use of signal
      scavenging for personnel detection.

PMID- 21096978
TI  - Design and fabrication of piezoelectric microactuators based on beta-poly
      (vinylidene fluoride) films for microfluidic applications.
AB  - This paper reports a fabrication method for producing piezoelectric poly
      (vinylidene fluoride) films in their electroactive beta-phase that features
      controlled thickness, smooth and flat surface, and high transparency. These
      piezoelectric films are suitable for being used as integrated microactuators,
      such as piezoelectric pumps and/or mixers, in microfluidic applications. Their
      actuation circuit design is also reported. ATR-FTIR, UV-VIS transmittance
      spectroscopy and SEM techniques were used for calculating the beta-phase content,
      for determining the transparency and for evaluating the morphology of the
      produced beta-PVDF films, respectively. beta-PVDF films with a thickness of about
      25 um were deposited by spin-coating. It was concluded that the processing
      parameter that mostly affect the films quality was their drying temperature.
      Indeed, the drying temperature of 30  degrees C proved to be the most suitable
      for obtaining non-porous and transparent films, with a beta-phase content of
      approximately 75%.

PMID- 21096979
TI  - MRI compatibility of microfabricated magnetic actuators for implantable
      catheters: Mechanical evaluations.
AB  - Here we demonstrate the mechanical robustness of microfabricated torsional
      magnetic actuators in withstanding the magnetic fields produced by a 7 T MRI
      magnet. The static and dynamic mechanical characteristics of 30 devices were
      quantitatively measured before and after exposure to both uniform and non-uniform
      magnetic fields. The results show no statistically significant change in both the
      static and dynamic mechanical performance, which mitigates concerns about the
      mechanical compatibility of our devices with MRI scanners. Additional experiments
      are required to quantify the potential image-artifact size and radio-frequency
      induced heating caused by the magnetic microactuators inside an MRI scanner.

PMID- 21096980
TI  - Artifact reduction based on Empirical Mode Decomposition (EMD) in
      photoplethysmography for pulse rate detection.
AB  - The pulstile components of photoplethysmography (PPG) contain valuable
      information about a subject's cardiovascular and metabolic systems. Pulse rate is
      one of the most significant vital signs that can be extracted from PPG signals.
      However, patient movement, especially movement at the measurement sites, such as
      fingers, can disturb the PPG's light path significantly, resulting in corrupted
      measurements. In this paper, a method is proposed for removing motion artifacts
      from PPG recordings. In this method, the Empirical Mode Decomposition (EMD) and
      Hilbert transform are used together to decompose PPG recordings into
      instantaneous frequency series on different scales of resolution. Motion
      artifacts and physiological signals are separated based on these series. The
      proposed method was used to recover PPG signals recorded in an experiment, where
      motion artifacts were intentionally introduced by finger bending. By using our
      method, the signal-to-noise ratio was increased from 0.078 dB of the contaminated
      signals to 0.318 dB, and the true detection rate of heartbeats was improved from
      59.2% to 96.6%. The results demonstrated that the EMD combined with Hilbert
      transform has great potential in reducing motion artifacts in PPG signals and can
      improve the accuracy of heartbeat detection.

PMID- 21096981
TI  - An ingestible wireless capsule for treatment of obesity.
AB  - Intragastric balloon has become a popular method for treatment of obesity due to
      its less-invasive and non-pharmaceutical procedure. In this method, a gas (or
      liquid)-filled balloon is inserted into the stomach using endoscopy or surgery.
      The balloon stays in and partially fills the stomach for a desired period of time
      to induce the feeling of satiety in the patient. At the end of the treatment
      period, the balloon is removed from the body using endoscopy or surgery. Although
      proven effective in treatment of obesity, this method suffers from several
      drawbacks. Requiring an endoscopic procedure or surgery to insert and exert the
      balloon from the stomach is the most important disadvantage of this method. These
      procedures are usually costly and may cause the patient to feel uncomfortable.
      Here, we propose a non-invasive method to overcome these drawbacks. In this
      method, an intragastric balloon is introduced into the body using an ingestible
      capsule. The volume of the capsule can be adjusted wirelessly after being
      swallowed by the patient. Using this method, a non-invasive and patient-specific
      treatment is possible.

PMID- 21096982
TI  - Motion generation of robotic surgical tasks: learning from expert demonstrations.
AB  - Robotic surgical assistants offer the possibility of automating portions of a
      task that are time consuming and tedious in order to reduce the cognitive
      workload of a surgeon. This paper proposes using programming by demonstration to
      build generative models and generate smooth trajectories that capture the
      underlying structure of the motion data recorded from expert demonstrations.
      Specifically, motion data from Intuitive Surgical's da Vinci Surgical System of a
      panel of expert surgeons performing three surgical tasks are recorded. The trials
      are decomposed into subtasks or surgemes, which are then temporally aligned
      through dynamic time warping. Next, a Gaussian Mixture Model (GMM) encodes the
      experts' underlying motion structure. Gaussian Mixture Regression (GMR) is then
      used to extract a smooth reference trajectory to reproduce a trajectory of the
      task. The approach is evaluated through an automated skill assessment
      measurement. Results suggest that this paper presents a means to (i) extract
      important features of the task, (ii) create a metric to evaluate robot imitative
      performance (iii) generate smoother trajectories for reproduction of three common
      medical tasks.

PMID- 21096983
TI  - Robotic-surgical instrument wrist pose estimation.
AB  - The Compact Lightweight Surgery Robot from the University of Hawaii includes two
      teleoperated instruments and one endoscope manipulator which act in accord to
      perform assisted interventional medicine. The relative positions and orientations
      of the robotic instruments and endoscope must be known to the teleoperation
      system so that the directions of the instrument motions can be controlled to
      correspond closely to the directions of the motions of the master manipulators,
      as seen by the the endoscope and displayed to the surgeon. If the manipulator
      bases are mounted in known locations and all manipulator joint variables are
      known, then the necessary coordinate transformations between the master and slave
      manipulators can be easily computed. The versatility and ease of use of the
      system can be increased, however, by allowing the endoscope or instrument
      manipulator bases to be moved to arbitrary positions and orientations without
      reinitializing each manipulator or remeasuring their relative positions. The aim
      of this work is to find the pose of the instrument end effectors using the video
      image from the endoscope camera. The P3P pose estimation algorithm is used with a
      Levenberg-Marquardt optimization to ensure convergence. The correct
      transformations between the master and slave coordinate frames can then be
      calculated and updated when the bases of the endoscope or instrument manipulators
      are moved to new, unknown, positions at any time before or during surgical
      procedures.

PMID- 21096984
TI  - Virtual environment to evaluate multimodal feedback strategies for augmented
      navigation of the visually impaired.
AB  - This paper proposes a novel experimental environment to evaluate multimodal
      feedback strategies for augmented navigation of the visually impaired. The
      environment consists of virtual obstacles and walls, an optical tracking system
      and a simple device with audio and vibrotactile feedback that interacts with the
      virtual environment, and presents many advantages in terms of safety,
      flexibility, control over experimental parameters and cost. The subject can
      freely move in an empty room, while the position of head and arm are tracked in
      real time. A virtual environment (walls, obstacles) is randomly generated, and
      audio and vibrotactile feedback are given according to the distance from the
      subjects arm to the virtual walls/objects. We investigate the applicability of
      our environment using a simple, commercially available feedback device.
      Experiments with unimpaired subjects show that it is possible to use the setup to
      "blindly" navigate in an unpredictable virtual environment. This validates the
      environment as a test platform to investigate navigation and exploration
      strategies of the visually impaired, and to evaluate novel technologies for
      augmented navigation.

PMID- 21096985
TI  - Design of a surgical robot with dynamic vision field control for Single Port
      Endoscopic Surgery.
AB  - Recently, a robotic system was developed to assist Single Port Endoscopic Surgery
      (SPS). However, the existing system required a manual change of vision field,
      hindering the surgical task and increasing the degrees of freedom (DOFs) of the
      manipulator. We proposed a surgical robot for SPS with dynamic vision field
      control, the endoscope view being manipulated by a master controller. The
      prototype robot consisted of a positioning and sheath manipulator (6 DOF) for
      vision field control, and dual tool tissue manipulators (gripping: 5DOF, cautery:
      3DOF). Feasibility of the robot was demonstrated in vitro. The "cut and vision
      field control" (using tool manipulators) is suitable for precise cutting tasks in
      risky areas while a "cut by vision field control" (using a vision field control
      manipulator) is effective for rapid macro cutting of tissues. A resection task
      was accomplished using a combination of both methods.

PMID- 21096986
TI  - Stochastic approach to error estimation for image-guided robotic systems.
AB  - Image-guided surgical systems and surgical robots are primarily developed to
      provide patient safety through increased precision and minimal invasiveness. Even
      more, robotic devices should allow for refined treatments that are not possible
      by other means. It is crucial to determine the accuracy of a system, to define
      the expected overall task execution error. A major step toward this aim is to
      quantitatively analyze the effect of registration and tracking-series of
      multiplication of erroneous homogeneous transformations. First, the currently
      used models and algorithms are introduced along with their limitations, and a
      new, probability distribution based method is described. The new approach has
      several advantages, as it was demonstrated in our simulations. Primarily, it
      determines the full 6 degree of freedom accuracy of the point of interest,
      allowing for the more accurate use of advanced application-oriented concepts,
      such as Virtual Fixtures. On the other hand, it becomes feasible to consider
      different surgical scenarios with varying weighting factors.

PMID- 21096987
TI  - Weighted LS-SVM for function estimation applied to artifact removal in bio-signal
      processing.
AB  - Weighted LS-SVM is normally used for function estimation from highly corrupted
      data in order to decrease the impact of outliers. However, this method is limited
      in size and big time series should be segmented in smaller groups. Therefore,
      border discontinuities represent a problem in the final estimated function.
      Several methods such as committee networks or multilayer networks of LS-SVMs are
      used to address this problem, but these methods require extra training and hence
      the computational cost is increased. In this paper a technique that includes an
      extra weight vector in the formulation of the cost function for the LS-SVM
      problem is proposed as an alternative solution. The method is then applied to the
      removal of some artifacts in biomedical signals.

PMID- 21096988
TI  - Support vector machine classification of multi-channel EEG traces: a new tool to
      analyze the brain response to morphine treatment.
AB  - The analgesic effect of morphine is highly individual, calling for objective
      methods to predict the subjective pain relief. Such methods might be based on
      alteration of brain response caused by morphine during painful stimuli. The study
      included 11 healthy volunteers subjectively quantifying perception of painful
      electrical stimulations in the esophagus. Brain evoked potentials following
      stimulations were recorded from sixty-four electroencephalographic channels at
      baseline and ninety minutes after morphine administration. Marginals obtained
      from discrete wavelet coefficients for each channel were used as input to an
      optimized support vector machine classifying between baseline and after morphine
      administration. The electroencephalographic channel leading to the best
      performance was further analyzed to identify brain alterations caused by
      morphine. Marginals from volunteers with no analgesic effect were examined for
      differences in comparison to volunteers with effect. The single-channel
      classification showed best performance at electrode P4 with 84.1 % of the traces
      classified correctly. When combining features from the 6 best performing
      channels, the multichannel classification increased to 92.4 %. The most
      discriminative feature was a decrease in the delta band (0.5 - 4 Hz) after
      morphine for volunteers with analgesic effect. Volunteers with no effect of
      morphine showed an increase in the delta band after drug administration. As only
      a proportion of patients benefit from opioid treatment, the new approach may help
      to identify non-responders and guide individualized tailored analgesic therapy.

PMID- 21096989
TI  - Non-invasive intracranial pressure estimation using support vector machine.
AB  - Intracranial Pressure (ICP) measurements are of great importance for the
      diagnosis, monitoring and treatment of many vascular brain disturbances. The
      standard measurement of the ICP is performed invasively by the perforation of the
      cranial scalp in the presence of traumatic brain injury (TBI). Measuring the ICP
      in a noninvasive way is relevant for a great number of pathologies where the
      invasive measurement represents a high risk. The method proposed in this paper
      uses the Arterial Blood Pressure (ABP) and the Cerebral Blood Flow Velocity
      (CBFV) - which may be obtained by means of non-invasive methods - to estimate the
      ICP. A non-linear Support Vector Machine was used and reached a low error between
      the real ICP signal and the estimated one, allowing an on-line implementation of
      the ICP estimation, with an adequate temporal resolution.

PMID- 21096990
TI  - Automatic error detection in the clinical measurement of gastric impedance
      spectra.
AB  - Gastric impedance spectroscopy has been proposed as a method of monitoring
      mucosal injury due to hypoperfusion and ischemia in the critically ill. During
      validation tests for this procedure, it was found that 60% of the measurements
      had errors by factors inherent to the clinical setting, indicating that some kind
      of automatic error detection should be incorporated to potentially avoid the loss
      of measurements. This paper presents an algorithm developed to detect errors due
      to bad connection, bad location or bad contact of the electrode probe. A labeled
      database with 20,908 sets of 92 spectral measurements each, obtained from
      critically ill patients was used as training/testing data. To reduce the
      dimensionality, the database was resized by dividing the spectral range into four
      bands, and then by computing mean and standard deviation in magnitude, phase,
      resistance and reactance for each band and measurement. Initial exploration into
      the data space was performed by k-means clustering, establishing the number of
      classes. Sequential Forward Selection was performed to determine best features
      from the reduced data set. Finally, Support Vector Machine classifiers were
      designed in a one-vs-rest hierarchical scheme to classify the quality of the
      spectra. Each classifier gave a hit rate greater than 95% and an area under the
      relative operating characteristic curve of 0.99. In a validation run with cardiac
      surgery and intensive care unit patient spectra, the error rates were 2.3% and
      8.4% respectively.

PMID- 21096991
TI  - Detection of periods of food intake using Support Vector Machines.
AB  - Studies of obesity and eating disorders need objective tools of Monitoring of
      Ingestive Behavior (MIB) that can detect and characterize food intake. In this
      paper we describe detection of food intake by a Support Vector Machine classifier
      trained on time history of chews and swallows. The training was performed on data
      collected from 18 subjects in 72 experiments involving eating and other
      activities (for example, talking). The highest accuracy of detecting food intake
      (94%) was achieved in configuration where both chews and swallows were used as
      predictors. Using only swallowing as a predictor resulted in 80% accuracy.
      Experimental results suggest that these two predictors may be used for
      differentiation between periods of resting and food intake with a resolution of
      30 seconds. Proposed methods may be utilized for development of an accurate,
      inexpensive, and non-intrusive methodology to objectively monitor food intake in
      free living conditions.

PMID- 21096992
TI  - A comprehensive motor symptom monitoring and management system: the bradykinesia
      case.
AB  - The current work describes a methodology to automatically detect the severity of
      bradykinesia in motor disease patients using wireless, wearable accelerometers.
      This methodology was tested with cross validation through a sample of 20
      Parkinson's disease patients. The assessment of methodology was carried out
      through some daily living activities which were detected using an activity
      recognition algorithm. The Unified Parkinson's Disease Rating Scale (UPDRS)
      severity classification of the algorithm coincides between 70 and 86% from that
      of a trained neurologist depending on the classifier used. These severities were
      calculated for 5 second segments of the signal with 50% of overlap. A
      bradykinesia profiler is also presented in this work. This profiler removes the
      overlap of the segments and calculates the confidence of the resulting events. It
      also calculates average severity, duration and symmetry values for those events.
      The profiler has been tested with a bogus dataset. Future work includes better
      training for the severity classifier with a larger sample and testing the
      profiler with real, longterm patient data in a projected pilot phase in three
      European hospitals.

PMID- 21096993
TI  - On-chip integrated lensless microscopy module for optical monitoring of adherent
      growing mammalian cells.
AB  - Lab-on-a-chip systems are increasingly applied in cell-based assays for
      toxicology and drug testing. In this paper, an on-chip integrated lensless
      microscopy module using a direct projection method for optical monitoring of the
      shadow images of adherent growing mammalian cells is presented. The biological
      cells are conserved and interfaced by a microfabricated cavity chip with a 1
      microm thick silicon nitride (Si(3)N(4)) substrate onto the surface of a 5
      megapixel CMOS image sensor with 2.2 microm pixel size. The optical resolution of
      the assembly is estimated by the contact/proximate printing theory from optical
      lithography. Further characterization is made by imaging microbeads in chips with
      the Si(3)N(4)-membrane as well as in cavity chips with membranes made from dry
      film resist (DFR, thickness 20, 40 and 60 microm). The module represents a 3 *
      optical microscope for cell morphology imaging. The function is demonstrated by
      the growth monitoring of L929 cells cultured in cavity chips with Si(3)N(4)
      substrate for 2 days and by checking the colorimetric staining of cells with a
      compromised membrane.

PMID- 21096994
TI  - OFSETH: A breathing motions monitoring system for patients under MRI.
AB  - The potential benefit of optical fiber sensors embedded into medical textiles for
      the continuous monitoring of patients for MRI is presented. We report a
      monitoring system based on the use of two novel non-intrusive optical sensing
      technologies designed to measure the elongation due to abdominal and thoracic
      motions during breathing. The developed system can successfully sense textile
      elongation between 0.1% and 5%, while maintaining the stretching properties of
      the textile substrates for a good comfort of the patient. The solution prototyped
      shows a high stability and good reproducibility. The sensors are coupled to a
      compact, real time and accurate monitoring system.

PMID- 21096995
TI  - Preliminary assessment of abdominal organ perfusion utilizing a fiber optic
      photoplethysmographic sensor.
AB  - In an attempt to overcome the limitations of current techniques for monitoring
      abdominal organ perfusion, a prototype reflectance fiber optic
      photoplethysmographic (PPG) sensor and processing system was evaluated on
      seventeen anaesthetized patients undergoing laparotomy. Good quality PPG signals
      were obtained from the large bowel, small bowel, liver and stomach. Simultaneous
      PPG signals from the finger were also obtained for comparison purposes using an
      identical fiber optic sensor. Analysis of the mean ac and dc PPG amplitudes of
      all acquired signals indicated larger amplitudes for those signals obtained from
      abdominal organs than those obtained from the finger. Mean estimated blood oxygen
      saturation (SpO(2)) values from all abdominal sites showed good agreement with
      those obtained from the finger using both the finger fiber optic sensor and a
      commercial finger pulse oximeter. Furthermore, a Bland and Altman between-method
      differences analysis on the estimated SpO(2) data suggests that a fiber optic
      abdominal sensor may be a suitable method for the evaluation of abdominal organ
      perfusion.

PMID- 21096996
TI  - Evaluation of a multimode photoplethysmographic sensor during cuff-induced
      hypoperfusion.
AB  - Photoplethysmography (PPG) is a technique widely used to monitor volumetric blood
      changes induced by cardiac pulsations. Pulse oximetry uses the technique of PPG
      to estimate arterial oxygen saturation values(S(p)O(2)). In poorly perfused
      tissues, S(p)O(2) readings may be compromised due to the poor quality of the PPG
      signals. We have developed a new multimode PPG measurement system which utilizes
      a reflectance PPG probe that operates in reflectance, transmittance and
      transreflectance mode simultaneously aiming to improve the quality of the PPG
      signals in cases of poor peripheral perfusion. In order to evaluate the
      performance of the probe, experiments were performed in healthy volunteers. A
      blood pressure cuff was used to induce systematic and controlled artificial
      hypoperfusion while PPG signals were recorded using all three modes. It was found
      that the amplitude of the transreflectance signal was significantly greater than
      the other two conventional PPG sensors at all occlusion pressures, suggesting the
      potential for improved signal acquisition in patients with peripheral
      hypoperfusion.

PMID- 21096998
TI  - Innovation in health care technology: is it part of the problem or part of the
      solution? eHealth gives the answer.
AB  - There is no doubt that the contribution of the Health Care Technologies to the
      tremendous evolution on Medicine since mid XX century has been one of its most
      important pillars. At the same time the innovation has been sometimes accused of
      been the root of the increase in the Health Care expenditure to support the
      Health of the society. Actually, when the Health Care Systems are focusing not
      only on the critical processes but on the continuum of the disease, the
      application of innovation to the chronic diseases and, more specifically, in the
      Cardiovascular ones (specially the Cardiac Insufficiency), represents a great
      challenge for care givers, patients and the Health Care Systems as their
      treatment requires continuous medical care and patient self management. The key
      for establishing this continuity of care in an efficient way is based in the
      concept of "Anticipation". This is the only way to avoid the burden of the
      continuous re-hospitalizations of this kind of patients. The engagement of
      patients in the adoption of healthy lifestyles with a positive impact in the
      progression of their diseases is fundamental to avoid the appearance of chronic
      complications or co-morbidities. Only with these assumptions the Innovation on
      Health Care Technologies will become part of the solution of the sustainability
      of the Health Care expenditure for the society. This paper present the keys for
      making the innovation efficient understanding the transversal of the Health Care
      processes.

PMID- 21096997
TI  - Bacterial biofilm disruption using laser generated shockwaves.
AB  - A system was built to test the efficacy of bacterial biofilm disruption using
      laser generated shockwaves. The system is based on a Q-switched, ND:YAG pulsed
      laser operating at a rep rate of 10 Hz with 1500 mJ pulses centered at 1064 nm.
      The laser pulses were used to create shockwave pulses in Al coated polycarbonate
      substrates and a resulting peak stress of greater than 50 MPa was measured. These
      stress pulses were coupled to bacteria grown to confluence on agar plates and
      cell death as a result of shockwave stress was assessed. The results show a 55%
      reduction in the number living bacteria between shocked and control samples. This
      type of biofilm disruption method could prove useful in the treatment of infected
      wounds where standard treatment methods such as debridement and topical
      antibiotics have proven to be ineffectual or harmful.

PMID- 21096999
TI  - Transcription factor activity estimation based on particle swarm optimization and
      fast network component analysis.
AB  - Transcription factors (TFs) play an important role in regulating the expression
      of genes. The accurate measurement of transcription factor activities (TFAs)
      depends on a series of experimental technologies of molecular biology and is
      intractable in most practical situations. Some signal processing methods for
      blind source separation have been applied in the prediction of TFAs from gene
      expression data. Most of such methods make use of statistical properties of the
      gene expression data only, leading to the inaccurate detection of TFAs. In
      contrast, network component analysis (NCA) can provide much improved result
      through utilizing the structural information of the gene regulatory network.
      However, the structure of the gene regulatory network, required by NCA, is not
      available in most practical cases so that NCA is not directly applicable. In this
      paper, we propose to use particle swarm optimization (PSO) to find the most
      plausible network structure iteratively from the gene expression data, with the
      assistance of recently developed fast algorithm for network component analysis
      (FastNCA). This novel approach to TFA inference can thus take advantage of NCA,
      even when the required network structure is unknown. The effectiveness of our
      novel approach has been demonstrated by applications to both simulated data and
      real gene expression microarray data, in the sense that TFAs can be inferred with
      high accuracy.

PMID- 21097000
TI  - Arrhythmia detection and classification using morphological and dynamic features
      of ECG signals.
AB  - Computer-assisted cardiac arrhythmia detection and classification can play a
      significant role in the management of cardiac disorders. In this paper, we
      propose a new approach for arrhythmia classification based on a combination of
      morphological and dynamic features. Wavelet Transform (WT) and Independent
      Component Analysis (ICA) are applied separately to each heartbeat to extract
      corresponding coefficients, which are categorized as 'morphological' features. In
      addition, RR interval information is also obtained characterizing the 'rhythm'
      around the corresponding heartbeat providing 'dynamic' features. These two
      different types of features are then concatenated and Support Vector Machine
      (SVM) is utilized for the classification of heartbeats into 15 classes. The
      procedure is applied to the data from two ECG leads independently and the two
      results are fused for the final decision. Compare the two classification results
      and the classification result is kept if the two are identical or the one with
      greater classification confidence is picked up if the two are inconsistent. The
      proposed method was tested over the entire MIT-BIH Arrhythmias Database [1] and
      it yields an overall accuracy of 99.66% on 85945 heartbeats, better than any
      other published results.

PMID- 21097001
TI  - Exploiting the ambiguity domain for non-stationary biomedical signal
      classification.
AB  - Research in time-frequency distributions (TFDs) is limited in terms of their use
      of the available spatial domains and in their target applications. Most of the
      work up till now has been concentrated mainly on the t-f domain space. This work
      presents a detailed study about the ambiguity domain (AD), their resemblance in
      the t-f space and the significance of using such a representation. Further, a
      novel approach for the analysis and classification between normal and
      pathological speech signals is also provided. The quantitative measures obtained
      show comparable performance scores with the existing schemes. Evidently, gait
      from 51-normal and 161-abnormal subjects were studied and classified in this
      analysis. Results obtained from the quantitative analysis illustrate comparable
      performance characteristics with some of the recent schemes and a maximum
      classification accuracy of 97.5% is obtained.

PMID- 21097002
TI  - Impact of movement on cardiorespiratory coordination in conscious rats.
AB  - In this study we assessed the impact of movement on the interaction between the
      heart rhythm and respiration in rats while they were conscious and freely moving.
      In eight male adult Sprague-Dawley (SD, n=4) and Hooded Wistar (HW, n=4) rats, we
      recorded respiratory rate using whole-body plethysmography with a piezoelectric
      sensor attached to simultaneously monitor body movement. Heart rate was recorded
      using a radio-telemetry transmitter. For the assessment of cardiorespiratory
      coordination, we analysed the phase-locking between heart rate and respiration,
      estimating the instantaneous phases using Hilbert transform. For statistical
      analysis, the piezoelectric signal was dichotomized into low-intensity (LIm) and
      high-intensity (HIm) movement. The R-R intervals, respiratory intervals and
      cardiorespiratory coordination between LIm and HIm of each rat were assessed with
      Student's t-test. A significant decrease in the mean values for respiratory
      interval (0.34 +/- 0.1 vs. 0.23 +/- 0.1 s, p < 0.01 in HW rats) and R-R interval
      (0.19 +/- 0.01 vs. 0.17 +/- 0.01 s, p < 0.001 in SD rats) was observed during
      HIm. The phase-locking between the cardiac and respiratory signals also decreased
      significantly during HIm (overall coordination during LIm vs. HIm: 89.3 +/- 3.3%
      vs. 8.7 +/- 1.7%, p < 0.001). In conclusion the interaction between the cardiac
      and respiratory oscillators is affected by voluntary movements in rats.

PMID- 21097003
TI  - Microrobotic navigable entities for Magnetic Resonance Targeting.
AB  - Magnetic Resonance Targeting (MRT) uses MRI for gathering tracking data to
      determine the position of microscale entities with the goal of guiding them
      towards a specific target in the body accessible through the vascular network. At
      full capabilities, a MRT platform designed to treat a human would consist of a
      clinical MRI scanner running special algorithms and upgraded to provide
      propulsion gradient up to approximately 400mT/m to enable entities as small as a
      few tens of micrometers in diameter and containing magnetic nanoparticles (MNP)
      to be steered at vessel bifurcations based on tracking information. Indeed, using
      a clinical MRI system, we showed that such single entity with a diameter as small
      as 15microm is detectable in gradient-echo scans. Among many potential
      interventions, targeted cancer therapy is a good initial application for such new
      microrobotic approach since secondary toxicity for the patient could be reduced
      while increasing therapeutic efficacy using lower dosages. Although many types of
      such entities are needed to provide a larger set of tools, here, only three
      initial types designed with different functionalities and for different types of
      cancer are briefly described. Initially designed for targeted chemo-embolization
      of liver tumors, the first type known as Therapeutic Magnetic Micro-Carriers
      (TMMC) consists in its present form of approximately 50 microm PLGA
      microparticles containing therapeutics and approximately 180 nm FeCo MNP. For the
      second type, MNP are not only used for propulsion and tracking, but also
      actuation based on a local elevation of the temperature. In its simplest form, it
      consists of approxiamtely 20 nm MNP embedded in a thermo-sensitive hydrogel known
      as PNIPA, allowing additional functionalities such as computer triggered drug
      release and targeted hyperthermia. The third type initially considered to target
      colorectal tumors, consists of 1-2 microm MR-trackable and controllable MC-1
      Magnetotactic Bacteria (MTB) with propelling thrust force provided by two
      flagella bundles per cell exceeding 4 pN.

PMID- 21097004
TI  - Toward tetherless insufflation of the GI Tract.
AB  - Toward increasing the diagnostic ability of wireless capsule endoscopy, we
      propose a method to wirelessly insufflate the Gastrointestinal Tract. By
      increasing the viewable surface area, it appears likely that capsule-based
      insufflation may reduce the number of false negative diagnoses made by endoscopic
      capsules. Our approach to wireless insufflation is to utilize controlled phase
      transition of a small volume of fluid stored onboard the capsule to a large
      volume of gas that is then emitted into the intestine. We begin by describing
      experiments designed to evaluate the amount of gas a capsule must produce to have
      a beneficial impact on visualization in the colon. We then describe experiments
      evaluating how much gas can be generated from a given volume of fluid, using
      Hydrogen Peroxide as our working fluid. We also evaluate thermal effects of the
      Hydrogen Peroxide reaction. The cumulative result of these experiments is an
      illustration of the feasibility of carrying a sufficient volume of fluid onboard
      a wireless capsule to generate a beneficial enhancement in visualization of the
      interior of the Gastrointestinal Tract, and specifically the colon.

PMID- 21097005
TI  - Optimal trajectory for a microrobot navigating in blood vessels.
AB  - The chemotherapy magnetically controlled under Magnetic Resonance Imaging (MRI)
      is currently one of the active areas of cancer research. This paper proposes a
      precise model of a therapeutic microrobot magnetically steered in blood vessels.
      This modeling approach takes into account the non-Newtonian behavior of blood, as
      well as wall effect on the blood's profile and robot-to-wall interaction forces.
      A backstepping approach law is used to ensure a null error between the real
      trajectory and an optimal reference trajectory deduced from the highly nonlinear
      model. The strengths and limitations of the overall study are evaluated by
      simulations.

PMID- 21097006
TI  - From miniature to nano robots for diagnostic and therapeutic applications.
AB  - This paper presents the evolution of diagnostic and therapeutic procedures as a
      process of convergence of technologies coming from different fields and involving
      different disciplines. In particular, it illustrates how modern surgery evolved
      thanks to fundamental biology knowledge; thus, with the introduction of imaging
      techniques intra-operatively and with the introduction of robotics, surgical
      procedures became much more predictable, precise and effective. Finally, the
      recent developments of optics (with CMOS and CCD technologies, and with the
      introduction of fiber optic technologies) allowed to "see" inside the human body,
      thus reducing the invasiveness of surgical procedures and making diagnostic
      procedures adequate for an effective early discovery of pathologies. Nowadays, we
      are assisting to a concrete merging between microrobotics technologies and
      bioengineering, with the potential to bring therapeutic tools where requested and
      when requested, with high precision and with very limited side effects.
      Furthermore, nanotechnology offers the possibility to fully implement this
      merging, thanks to the development of dedicated theranostic nanotools suitably
      fitting the considered convergence scenario.

PMID- 21097008
TI  - Electromagnetic actuation methods for intravascular locomotive microrobot.
AB  - Heart diseases such as angina pectoris and myocardial infarction have been
      becoming the leading causes of death all over the world in recent years. The
      pharmacotherapy and the surgical operations have been executed for treating heart
      problems. The percutaneous coronary intervention (PCI) with catheter is
      frequently used for the treatment of coronary artery diseases, but the treatment
      of chronic total occlusion (CTO) is very difficult and challenging operation,
      since there is no efficient alternative therapy until now. For this reason, the
      microrobot to improve the intravascular treatment is one of the growing research
      areas. In this paper, various electromagnetic actuation (EMA) systems to supply
      driving power for the microrobot were proposed. The performance of the locomotion
      of microrobot in the 2D and 3D space were validated with in-vitro experiments and
      also the in-vivo tests were performed for demonstrating the movement of
      microrobot in the living rabbit.

PMID- 21097007
TI  - Oxygen sensing using microrobots.
AB  - We present a luminescence oxygen sensor incorporated in a wireless intraocular
      microrobot for minimally-invasive diagnosis. This microrobot can be accurately
      controlled in the intraocular cavity by applying magnetic fields. The microrobot
      consists of a magnetic body susceptible to magnetic fields and a sensor coating.
      This coating embodies Pt(II) octaethylporphine (PtOEP) dyes as the luminescence
      material and polystyrene as a supporting matrix, and it can be wirelessly excited
      and read out by optical means. The sensor works based on quenching of
      luminescence in the presence of oxygen. The excitation and emission spectrum,
      response time, and oxygen sensitivity of the sensor were characterized using a
      spectrometer. A custom device was designed and built to use this sensor for
      intraocular measurements with the microrobot. Due to the intrinsic nature of
      luminescence lifetimes, a frequency-domain lifetime measurement approach was
      employed. An alternative sensor implementation using poly(styrene-co-maleic
      anhydride) (PS-MA) and PtOEP was successfully demonstrated with nanospheres to
      increase sensor performance.

PMID- 21097009
TI  - Sparsity-promoting fluorescence molecular tomography with iteratively reweighted
      regularization.
AB  - Fluorescence molecular tomography has become a promising technique for in vivo
      small animal imaging, and has many potential applications. Due to the ill-posed
      and the ill-conditioned nature of the problem, Tikhonov regularization is
      generally adopted to stabilize the solution. However, the result is usually over
      smoothed. In this study, the sparsity of the fluorescent source is used as a
      priori information. We replace Tikhonov method with an iteratively reweighted
      scheme. By dynamically updating the weight matrix, L0- or L1-norm regularization
      can be approximated which can promote the sparsity of the solution. Simulation
      study shows that this method can preserve the sparsity of the fluorescent source
      within heterogeneous medium, even with very limited measurement data.

PMID- 21097010
TI  - Control of action potential duration alternans in canine ventricular tissue.
AB  - Cardiac action potential duration alternans is characterized by a beat-to-beat
      alternation in action potential waveform. Its presence has been putatively linked
      to the onset of lethal cardiac arrhythmias. Previous studies, which have been
      limited to cardiac Purkinje fibers, have shown that closed-loop alternans control
      techniques, which apply a succession of externally administered cycle
      perturbations, provide ineffectual spatial alternans elimination. A more complete
      understanding of alternans control in the more clinically relevant ventricular
      tissue is needed. Here, we study the spatial dynamics of alternans and alternans
      control in arterially perfused canine right ventricular preparations using
      optical mapping. We quantified the spatial efficacy of alternans control across
      2.5 cm of tissue, focusing primarily on differences in spatial control within
      several sub-regions of tissue. Our results provide a basis for future
      investigations into multi-electrode-based control interventions of alternans in
      cardiac tissue.

PMID- 21097012
TI  - Tracking training evolution: patient with upper limb amputation above the elbow.
AB  - This article describes a patient training evolution to achieve myoelectric
      control in the remnant limb. The methodology is divided in two main stages: (i)
      the training procedure, where the patient is submitted to a protocol for
      educating the muscles of the remnant limb, and (ii) myoelectric signal
      acquisition and analysis, in order to measure the patient evolution to reach
      different contraction levels along the training sessions. After three training
      stages, the results suggest that the patient gradually achieved strength control
      over the muscles of the remnant limb.

PMID- 21097011
TI  - Integrated versus isolated training of the hemiparetic upper extremity in
      haptically rendered virtual environments.
AB  - This paper describes the preliminary results of an ongoing study of the effects
      of two training approaches on motor function and learning in persons with hemi
      paresis due to cerebrovascular accidents. Eighteen subjects with chronic stroke
      performed eight, three-hour sessions of sensorimotor training in haptically
      renedered environments. Eleven subjects performed training activities that
      integrated hand and arm movement while another seven subjects performed
      activities that trained the hand and arm with separately. As a whole, the
      eighteen subjects made statistically significant improvements in motor function
      as evidenced by robust improvements in Wolf Motor Function Test times and
      corresponding improvements in Jebsen Test of Hand Function times. There were no
      significant between group effects for these tests. However, the two training
      approaches elicited different patterns and magnitudes of performance improvement
      that suggest that they may elicit different types of change in motor learning and
      or control.

PMID- 21097013
TI  - Enhancing robotic gait training via augmented feedback.
AB  - Recent work has examined the feasibility of robotic-assisted gait training in
      pediatric patients, including children with cerebral palsy (CP). Herein we
      present a case series describing clinical outcomes in four children with CP who
      underwent gait training using a robotic driven gait orthosis (DGO) (Pediatric
      Lokomat(c)). Children had a diagnosis of spastic diplegia due to CP. They were
      paired based on functional abilities and observed gait characteristics. Two
      children had a GMFCS of III and showed excessive ankle plantarflexion during
      stance. The other two children had a GMFCS of II and displayed a crouch gait
      pattern. Each subject participated in a 6-week intervention of robotic-assisted
      gait training that involved three 30-minute sessions per week. Pre-and post
      training evaluations were performed including clinical tests of standing and
      walking function, walking speed, and walking endurance. Clinical gait analysis
      was also performed using a motion capture system to assess changes in gait
      mechanics. All subjects showed an improvement in locomotor function. For lower
      functioning children, this may be mediated by improved trunk control. The use of
      augmented feedback was associated with larger. However, these results have to be
      considered with caution because of the limited sample size of the study.

PMID- 21097014
TI  - Evaluation in vitro of a treatment planning algorithm for an epicardial crawling
      robot.
AB  - HeartLander is a small, mobile robot designed to assist surgical procedures on
      the surface of the heart. It crawls within the pericardial sac surrounding the
      heart. Numerous potential clinical uses for HeartLander involve injections or
      other interventions at multiple locations on the epicardial surface. To minimize
      treatment time, we have developed an algorithm that optimizes a plan for reaching
      a given set of treatment targets. Results from in vitro evaluation on a beating
      heart model show improvement over a greedy technique.

PMID- 21097015
TI  - Disposable endoscope tip actuation design and robotic platform.
AB  - A disposable endoscopic platform with actuation motors inside the body of the
      endoscope is presented. This platform can enable new medical devices for
      diagnosis and for minimally invasive surgeries. This paper addresses mechanical
      and safety issues with existing endoscope technologies by incorporating
      disposability, safety modules, and lower cable forces. In order to produce path
      independent cable forces, motors are incorporated in the body of the endoscope
      near the bending tip. Results for tip forces are shown accompanied by an
      analytical model describing the scaling laws for this type of robotic
      architecture. The system under development will provide a platform for research
      into haptic control and perceptual feedback.

PMID- 21097016
TI  - Towards direct head navigation for robot-guided transcranial magnetic stimulation
      using 3D laserscans: Idea, setup and feasibility.
AB  - Direct tracking is more robust than tracking that is based on additional markers.
      3D laser scans can be used for direct tracking because they result in a 3D data
      set of surface points of the scanned object. For head-navigated robotized
      systems, it is crucial to know where the patient's head is positioned relatively
      to the robot. We present a novel method to use a 3D laserscanner for direct head
      navigation in the robotized TMS system that places a coil on the patient's head
      using an industrial robot. First experimental results showed a translational
      error < 2mm in the robot hand-eye-calibration with the laserscanner. The
      rotational error was 0.75 degrees  and the scaling error < 0.001. Furthermore, we
      found that the error of a scanned head to a reference head image was < 0.2mm
      using ICP. These results have shown that a direct head navigation is feasible for
      the robotized TMS system. Additional effort has to be made in future systems to
      speed up the compution time for real time capability.

PMID- 21097017
TI  - On the controllability of dynamic model-based needle insertion in soft tissue.
AB  - Soft tissue needle guidance and steering for clinical applications has been an
      active topic of research in the past decade. Although dynamic feedback control of
      needle insertion systems is expected to provide more accurate target tracking, it
      has received little attention due to the fact that most available models for
      needle-tissue interaction do not incorporate the dynamics of motions. In this
      paper, we study the controllability of rigid or flexible needles inside soft
      tissues using mechanical-based dynamic models. The results have significant
      implications on the design of suitable feedback controllers for different types
      of needle insertion systems.

PMID- 21097018
TI  - A compact dynamic force model for needle-tissue interaction.
AB  - In this paper, the interaction force between a surgical needle and soft tissue is
      studied. The force is modeled using nonlinear dynamics based on a modified LuGre
      model that captures all stages of needle-tissue interaction including puncture,
      cutting, and friction forces. An estimation algorithm for identifying the
      associated parameters is then presented. This approach, which is based on
      extended Kalman filtering (EKF), enables us to characterize the interaction with
      a mathematical model in the force domain. It compares the axial force measured at
      the needle base with its expected value and then adapts the model parameters to
      represent the actual interaction. To evaluate the performance of our model,
      experiments were performed on an artificial phantom.

PMID- 21097019
TI  - Accuracy study of a new assistance system under the application of Navigated
      Control(r) for manual milling on a head phantom.
AB  - In this article, a technical study of a new assistance system to support surgeons
      in milling on the temporal bone is presented. In particular, the overall accuracy
      of a new assistance system was investigated experimentally under conditions close
      to surgical practice. For the experiment, the assistance system has been used
      with its associated navigation system for ear-nose-throat (ENT) surgery. A
      specially constructed head phantom allowed the implementation of reproducible
      experiments. Thereby, N = 10 specimens were milled by three test persons without
      medical knowledge and the distance between points on the milled surface and the
      security zone around the planned nerve for each specimen were calculated. The
      result was as follows: None of the 10 milled specimens overlapped more than 2mm
      with the security zone, the average distances to the planned surface of the
      security zone for each specimen were between 0.01mm and 2.23mm, and the
      corresponding standard deviations varied from 0.41mm to 1.17mm. But it also shows
      some variation in averages and standard deviations and it was often too little
      material removed. This deviation is probably caused by the patient registration
      and the tool calibration.

PMID- 21097020
TI  - How accurate is accurate enough? A brief overview on accuracy considerations in
      image-guided cardiac interventions.
AB  - Image-guided interventions have revolutionized the development of minimally
      invasive surgical procedures, leading to reduced patient trauma, fewer risks and
      shorter recovery times. However, one of the most frequently posed question with
      regards to an image guidance system is how accurate it is. In this work we
      provide a brief overview on accuracy considerations from our perspective on
      cardiac image-guided procedures: what are the clinically-imposed accuracy
      constraints, how do these measure against the limitations of the image-guidance
      system, and how can surgeons directly benefit from real-time accuracy feedback to
      ensure optimal navigation at all times during the intervention?

PMID- 21097021
TI  - Electromyographic assessment of muscle fatigue during isometric vibration
      training at varying frequencies.
AB  - Resistance exercise is essential to improve or maintain muscle performance.
      Vibration training has been suggested as an alternative option for muscle
      conditioning, aiming especially at improving muscle strength and power. Several
      studies link the effects of vibration training to enhanced neuromuscular
      stimulation, measured by electromyography (EMG) and typically ascribed to
      involuntary reflex mechanisms. However, the underlying mechanisms are still
      unclear, limiting the use of vibration training. This paper proposes additional
      methods to analyze the mechanisms involved in vibration training. A dedicated
      measurement setup was realized to relate vibration parameters to muscle fatigue
      in the biceps brachii. Fatigue is estimated by EMG mean frequency and conduction
      velocity assessments as well as by maximum voluntary contraction (MVC) force
      measurements. A modified maximum likelihood algorithm is proposed for the
      conduction velocity estimation based on high-density EMG recording. Five
      volunteers performed four isometric contractions of 50 s at 80% MVC with no
      vibration (control) and with superimposed vibration at 20, 30, and 40 Hz. Fatigue
      was estimated from the decay of force, EMG mean frequency, and EMG conduction
      velocity. 30-Hz vibrations represented the most fatiguing stimulus. Our
      preliminary results also show a better correlation between force and conduction
      velocity decay than between force and mean frequency decay, indicating the former
      as a better EMG indicator of fatigue. The proposed methods provide important
      advancements for the analysis of vibration exercise and guidance towards the
      definition of optimal training protocols.

PMID- 21097022
TI  - Statistical characterization of actigraphy data during sleep and wakefulness
      states.
AB  - Human activity can be measured with actimetry sensors used by the subjects in
      several locations such as the wrists or legs. Actigraphy data is used in
      different contexts such as sports training or tele-medicine monitoring. In the
      diagnosis of sleep disorders, the actimetry sensor, which is basically a 3D axis
      accelerometer, is used by the patient in the non dominant wrist typically during
      an entire week. In this paper the actigraphy data is described by a weighted
      mixture of two distributions where the weight evolves along the day according to
      the patient circadian cycle. Thus, one of the distributions is mainly associated
      with the wakefulness state while the other is associated with the sleep state.
      Actigraphy data, acquired from 20 healthy patients and manually segmented by
      trained technicians, is used to characterize the acceleration magnitude during
      sleep and wakefulness states. Several mixture combinations are tested and
      statistically validated with conformity measures. It is shown that both
      distributions can co-exist at a certain time with varying importance along the
      circadian cycle.

PMID- 21097023
TI  - GNL-HybELS: an algorithm to classify and identify VOR responses simultaneously.
AB  - The Vestibulo-Ocular Reflex (VOR) stabilizes the images of the world on the
      retinae when the head is in motion. Basic daily activities such as walking or
      driving depend on the proper functioning of this reflex. For several decades,
      scientists have developed methods to model and identify this system
      mathematically. However, traditional methods cannot analyze VOR data
      comprehensively because they disregard pieces of data (fast phases) which biases
      estimated reflex dynamics. Here we propose, for the first time, an automated tool
      to analyze entire VOR responses (slow and fast phases), without apriori
      classification of nystagmus segments.

PMID- 21097024
TI  - Identification of sources of low frequency variability of arterial blood
      pressure: cardiac output acts as a buffer and not as a source.
AB  - Arterial blood pressure (ABP) short term variability is due to beat-by-beat
      fluctuations in cardiac output (CO) and total peripheral resistance (TPR), which
      have distinct effects at low and high frequencies. In particular, it was shown
      that CO is able to buffer TPR slow oscillations in the LF band, but it has not
      been addressed if CO can contribute to oscillations of ABP in this band. In this
      paper, we propose a model for the identification of ABP variability sources, in
      order to show evidence that CO fluctuations are not a source of ABP LF
      oscillations, but they only buffer ABP variability of vasomotor origin.

PMID- 21097025
TI  - Dcm-ar: a fast flash-based Web-PACS viewer for displaying large DICOM images.
AB  - Using Web-PACS has become an attractive option that brings access to medical
      imaging databases from remote hosts. However, the big size of the medical images
      to be transmitted impacts negatively on the teleradiologist experience by
      increasing the dead times elapsed between study request and visualization on the
      screen. In this context, it is of the upmost interest to implement strategies to
      optimize image transmission. In this work a system (Dcm-Ar) for remote
      visualization of DICOM files is presented, which strongly reduces the time-to
      display (TTD), thus improving the teleradiologist comfort. Dcm-Ar is made up of a
      Server interacting with a PACS and a remote Client. The Client is a DICOM viewer,
      which is based on the Adobe Flash virtual machine. This fact ensures easy and
      costless dissemination of the technology.

PMID- 21097026
TI  - Grid infrastructures for developing mammography CAD systems.
AB  - This paper presents a set of technologies developed to exploit Grid
      infrastructures for breast cancer CAD, that include (1) federated repositories of
      mammography images and clinical data over Grid storage, (2) a workstation for
      mammography image analysis and diagnosis and (3) a framework for data analysis
      and training machine learning classifiers over Grid computing power specially
      tuned for medical image based data. An experimental mammography digital
      repository of approximately 300 mammograms from the MIAS database was created and
      classifiers were built achieving a 0.85 average area under the ROC curve in a
      dataset of 100 selected mammograms with representative pathological lesions and
      normal cases. Similar results were achieved with classifiers built for the UCI
      Breast Cancer Wisconsin dataset (699 features vectors). Now these technologies
      are being validated in a real medical environment at the Faculty of Medicine in
      Porto University after a process of integrating the tools within the clinicians
      workflows and IT systems.

PMID- 21097027
TI  - Microphonics in biopotential measurements with capacitive electrodes.
AB  - Biopotential measurements with capacitive electrodes do not need any direct
      contact between electrode and skin, which saves the time devoted to expose and
      prepare the contact area when measuring with conductive electrodes. However,
      mechanical vibrations resulting from physiological functions such as respiration
      and cardiac contraction can change the capacitance of the electrode and affect
      the recordings. This transformation of mechanical vibrations into undesired
      electric signals is termed microphonics. We have evaluated microphonics in
      capacitive ECG recordings obtained from a dressed subject seated on a common
      chair with electrodes placed on the front side of the backrest of the chair.
      Depending on the softness of the backrest, the recordings may be clearly affected
      by the displacement of the thorax back wall due to the respiration and to the
      heart's mechanical activity.

PMID- 21097028
TI  - A 64-channel readout ASIC for nanowire biosensor array with electrical
      calibration scheme.
AB  - A 1.8-mW, 18.5-mm(2) 64-channel current readout ASIC was implemented in 0.18-um
      CMOS together with a new calibration scheme for silicon nanowire biosensor
      arrays. The ASIC consists of 64 channels of dedicated readout and conditioning
      circuits which incorporate correlated double sampling scheme to reduce the effect
      of 1/f noise and offset from the analog front-end. The ASIC provides a 10-bit
      digital output with a sampling rate of 300 S/s whilst achieving a minimum
      resolution of 7 pA(rms). A new electrical calibration method was introduced to
      mitigate the issue of large variations in the nano-scale sensor device parameters
      and optimize the sensor sensitivity. The experimental results show that the
      proposed calibration technique improved the sensitivity by 2 to 10 times and
      reduced the variation between dataset by 9 times.

PMID- 21097029
TI  - Cole parameter estimation from electrical bioconductance spectroscopy
      measurements.
AB  - Several applications of Electrical Bioimpedance (EBI) make use of Cole parameters
      as base of their analysis, therefore Cole parameters estimation has become a very
      common practice within Multifrequency- and EBI spectroscopy. EBI measurements are
      very often contaminated with the influence of parasitic capacitances, which
      contributes to cause a hook-alike measurement artifact at high frequencies in the
      EBI obtained data. Such measurement artifacts might cause wrong estimations of
      the Cole parameters, contaminating the whole analysis process and leading to
      wrong conclusions. In this work, a new approach to estimate the Cole parameters
      from the real part of the admittance, i.e. the conductance, is presented and its
      performance is compared with the results produced with the traditional fitting of
      complex impedance to a depressed semi-circle. The obtained results prove that is
      feasible to obtain the full Cole equation from only the conductance data and also
      that the estimation process is safe from the influence capacitive leakage.

PMID- 21097030
TI  - Surface acoustic wave resonators as novel tools for multiparametric blood
      analysis.
AB  - In this paper a new tool to assess viscoelastic and dielectric properties of
      human fluids is presented. Shear horizontal polarized surface acoustic waves (SH
      SAW) are used to detect the viscoelastic properties of coagulating blood and
      blood plasma samples. One-port SAW resonators, with fundamental modes of 85, 170
      und 340 MHz were developed. Additionally, their electrode structures can be used
      simultaneously to detect the dielectric behavior of the whole system by impedance
      spectroscopy while the frequency ranges from kHz to MHz. The combination of both
      methods offers the detection of clinical relevant blood parameters like the blood
      coagulation time and the hematocrit value within one measurement.

PMID- 21097031
TI  - Flexible PDMS -based dry electrodes for electro-optic acquisition of ECG signals
      in wearable devices.
AB  - We present a new type of flexible dry copper electrodes based on
      Polydimethylsiloxane (PDMS) coatings, requiring no electrical contact with the
      body. Tests were performed in order to evaluate the performance of these types of
      electrodes using electro-optic techniques, suitable for wearable devices.
      Conductive and insulated PDMS layers were fabricated through a spin coating
      process, reaching a thickness of 100u. These layers were then deposited on top of
      a flexible copper sheet. In a first set of experiments PDMS-based electrodes were
      compared with Ag/AgCl pre-gelled electrodes, showing comparable performances and
      lower noise signals. In order to test the influence of electrode area into signal
      strength, different sizes were chosen: 10.14 cm(2), 17.55 cm(2), 25.3 cm(2) and
      39 cm(2). The results have shown that the signal strength increases with
      electrode area. We have also tested the influence of PDMS conductivity in signal
      strength, by adding two types of nickel to the pre-polymer solution. PDMS
      conductive electrodes have shown slightly better performances, with amplitudes
      higher than 200mV, which is the maximum value recorded with PDMS insulated
      electrodes.

PMID- 21097032
TI  - High-k dielectric fabrication process to minimize mobile ionic penetration.
AB  - A process for fabricating hafnium oxide (HfO) films to minimize ionic penetration
      was developed and tested. A 333A HfO film was successfully deposited by thermal
      evaporation. The film was characterized through capacitance versus time (C-T) and
      capacitance versus voltage (C-V) measurements. The films were exposed to a
      solution of 0.1M NaCl physiological saline and preliminary results showed that
      the ionic species did not alter the electrical characteristics. The relative
      effective dielectric constant of the hafnium oxide layer and SiO(2) interfacial
      layer was 10.5, while the relative dielectric constant of the hafnium oxide layer
      was 18.

PMID- 21097033
TI  - Synergy matrices to extract fluid wrist motion intents via surface
      electromyography.
AB  - This paper presented an estimation method of multi-directional and proportional
      fluid wrist motion intents via sEMG using a non-negative muscle synergy matrix
      and a joint synergy matrix. A real-time experiment was performed to validate
      feasibility of the proposed method, and the experimental environment was realized
      for the individuals with wrist amputation. Only four wrist movements were
      predefined (wrist extension, wrist flexion, radial deviation, and ulnar
      deviation), but the experimental results showed that fluid wrist motion intents
      (e.g. a combination of wrist extension and ulnar deviation) could be extracted.
      This work could be useful for the people with wrist amputations to restore their
      wrist functions using myoelectric powered wrist prosthesis, and also for research
      to investigate how humans learn myoelectric controls in two-dimensions via
      training.

PMID- 21097034
TI  - Myoelectric control of a powered knee prosthesis for volitional movement during
      non-weight-bearing activities.
AB  - This paper describes a means of controlling the knee movement of a powered knee
      prosthesis during non-weight-bearing activity such as sitting, by utilizing
      surface EMG from the quadriceps and hamstring muscle groups in the residual limb.
      The method was implemented on a powered prosthesis on three amputee subjects, and
      experimental results are presented characterizing the ability of the amputee
      subjects to control knee motion. A comparison of the trajectory tracking error
      between the amputees' prosthetic and intact knees indicates that the EMG-based
      volitional controller provides similar trajectory tracking capability to the
      native (i.e., intact) knee joint.

PMID- 21097035
TI  - Principal components of frequency domain electromyograms for muscular fatigue
      analysis.
AB  - The parameters commonly employed for muscular fatigue (MF) analysis, the mean
      frequency (F(mean)) and median frequency (F(median)) of surface EMG (SEMG)
      spectra, did not present consistent results for exercises performed at low to
      moderate intensities. For overcoming this limitation, the present study proposes
      the use of principal component (PC) analysis of SEMG spectra for MF monitoring.
      The SEMG from vastus lateralis muscle of 24 young male subjects were recorded
      during a maximal effort test in cycle ergometer. Epochs of 200 ms SEMG, extracted
      from each period of muscle activation of each subject were used for estimating
      the amplitude spectra, which were employed to obtain the first two PCs. The PC
      coefficients from the first 40 spectra were used as a reference for calculating
      the standard distance. This index presented a consistent increase along the
      exercise, while the values of F(mean) and F(median) did not present any pattern.
      Comparisons between initial and final values from all subjects show no
      significant changes in F(mean) and F(median) (Student t test, P > 0.05) and a
      significant increase (P < 10(-3)) in standard distance, indicating this index as
      an alternative to MF analysis in cyclical exercises.

PMID- 21097036
TI  - Torque prediction using stimulus evoked EMG and its identification for different
      muscle fatigue states in SCI subjects.
AB  - Muscle fatigue is an unavoidable problem when electrical stimulation is applied
      to paralyzed muscles. The detection and compensation of muscle fatigue is
      essential to avoid movement failure and achieve desired trajectory. This work
      aims to predict ankle plantar-flexion torque using stimulus evoked EMG (eEMG)
      during different muscle fatigue states. Five spinal cord injured patients were
      recruited for this study. An intermittent fatigue protocol was delivered to
      triceps surae muscle to induce muscle fatigue. A hammerstein model was used to
      capture the muscle contraction dynamics to represent eEMG-torque relationship.
      The prediction of ankle torque was based on measured eEMG and past measured or
      past predicted torque. The latter approach makes it possible to use eEMG as a
      synthetic force sensor when force measurement is not available in daily use. Some
      previous researches suggested to use eEMG information directly to detect and
      predict muscle force during fatigue assuming a fixed relationship between eEMG
      and generated force. However, we found that the prediction became less precise
      with the increase of muscle fatigue when fixed parameter model was used.
      Therefore, we carried out the torque prediction with an adaptive parameters using
      the latest measurement. The prediction of adapted model was improved with 16.7%
      50.8% comparing to the fixed model.

PMID- 21097037
TI  - Filterbank spectral estimators for the analysis of surface EMG signals during
      isometric contractions.
AB  - The analysis of surface electromyogram (EMG) signals during voluntary isometric
      contractions can yield important information relating to muscle fatigue. These
      EMG signals are typically processed to extract specific variables such as the
      Mean Frequency (MNF) and the Median Frequency (MDF) and studies often follow how
      these parameters change through time. Traditional approaches to estimate the MNF
      and MDF variables are based on the periodogram, but this method suffers from a
      high degree of variability due in part the choice of window size, window function
      and other inherent limitations. In this paper we propose the use of data-adaptive
      filterbank spectral analysis techniques, namely the Power Spectrum Capon (PSC)
      and the Amplitude Spectrum Capon (ASC) methods. These new methods are shown to
      provide significant reductions in MNF and MDF parameter variability over a wide
      range of data window sizes.

PMID- 21097038
TI  - Recognition of forearm muscle activity by continuous classification of multi-site
      mechanomyogram signals.
AB  - Recent studies on identifying multiple activation states from mechanomyogram
      (MMG) signals for the purpose of controlling switching interfaces have employed
      pattern recognition methods where MMG signal features from multiple muscle sites
      are extracted and classified. The purpose of this study is to determine if MMG
      signal features retain enough discriminatory information to allow reliable
      continuous classification, and to determine if there is a decline in
      classification accuracy over short time periods. MMG signals were recorded from
      two accelerometers attached to the flexor carpi radialis and extensor carpi
      radialis muscles of 12 able-bodied participants as participants performed three
      classes of forearm muscle activity. The data were collected over five recording
      sessions, with a ten-minute interval between each session. The data were spliced
      into 256 ms epochs, and a comprehensive set of signal features was extracted. A
      pattern classifier, trained with continuously acquired signal features from the
      first recording session, was tested with signals recorded from the other
      sessions. The average classification accuracy over the five sessions was 89 +/-
      2%. There was no obvious declining trend in classification accuracy with time.
      These results show that MMG signals recorded at the forearm retain enough
      discriminatory information to allow continuous recognition of hand motion across
      multiple (>90) repetitions, and the MMG-classifier does not show short-term
      degradation. These results indicate the potential of MMG as a multifunction
      control signal for muscle-machine interfaces.

PMID- 21097039
TI  - BEM simulations of Rayleigh wave propagation in media with microstructural
      effects: Application to long bones.
AB  - Bone is a strongly heterogeneous natural composite with microstructure. Although
      the classical theory of linear elasticity has been largely used in bone
      ultrasonic studies, it cannot sufficiently describe the mechanical behavior of
      materials with microstructure. Furthermore, this theory predicts non-dispersive
      behavior of Rayleigh waves, which is in conflict with experimental observations.
      By using the simplest theory of gradient elasticity we recently demonstrated that
      bone's microstructure significantly affects the dispersion of classical Lamb
      modes. In this work, we investigate the effect of bone's microstructure on the
      propagation of Rayleigh waves by using the Boundary Element Method (BEM). We
      assume an isotropic semi-infinite space with mechanical properties equal to those
      of bone and microstructure. Microstructural effects are taken into account by
      introducing in the stress analysis the internal length scale parameters l(1),
      l(2), h(1), h(2). BEM computations are performed for various combinations of
      these parameters with values empirically chosen close to the osteon's size. The
      constants' values are also compared to those derived from closed form relations.
      The results made clear that bone's microstructure significantly affects Rayleigh
      wave dispersion.

PMID- 21097040
TI  - Low-power circuits design for the wireless force measurement system of the total
      knee arthroplasty.
AB  - This paper proposes a novel wireless force measurement system for the Total Knee
      Arthroplasty (TKA) to improve the ligament balancing procedure during TKA. The
      force measurement system is comprised of a Wireless Force Measurement Spacer
      (WFMS) and the display part. They communicate with each other by the Radio
      Frequency (RF) signal. The WFMS is designed to measure the force between the WFMS
      and the femoral component of the artificial implants and to transmit the force
      data wirelessly by a low power transceiver. The display part demonstrates the
      force data in 3D images in real time. The WFMS composes of a sensors array, a
      Universal Transducer Interfaces (UTIs) array, a low-power sub-threshold
      microprocessor and a transceiver. The sub-threshold 8-bit microprocessor is taped
      out with 0.18 microm CMOS technology. The testing results of the microprocessor
      show that the leakage power of 46nW and the dynamic power of 385nW@165kHz are
      achieved with the operating voltage of 350 mV. The test results of the system are
      given and the errors of the system are analyzed. The results verified the
      reliability of the system. The future work is to design the microprocessor and a
      lower power transceiver within a single chip.

PMID- 21097042
TI  - Robust pulse wave velocity estimation by application of system identification to
      proximal and distal arterial waveforms.
AB  - Pulse wave velocity (PWV) is a marker of arterial stiffness and may permit
      continuous, non-invasive, and cuff-less monitoring of blood pressure. Here,
      robust PWV estimation was sought by application of system identification to
      proximal and distal arterial waveforms. In this approach, the system that
      optimally couples the proximal waveform to the distal waveform is identified, and
      the time delay of this system is then used to calculate PWV. To demonstrate proof
      of-concept, a standard identification technique was applied to non-invasive
      impedance cardiography and peripheral arterial blood pressure waveforms from six
      humans subjected to progressive reductions in central blood volume induced by
      lower body negative pressure. This technique estimated diastolic pressure with an
      overall root-mean-squared-error of 5.2 mmHg. For comparison, the conventional
      detection method for estimating PWV yielded a corresponding error of 8.3 mmHg.

PMID- 21097041
TI  - Accuracy considerations in catheter based estimation of left ventricular volume.
AB  - Cardiac volume estimation in the Left Ventricle from impedance or admittance
      measurement is subject to two major sources of error: parallel current pathways
      in surrounding tissues and a non uniform current density field. The accuracy of
      volume estimation can be enhanced by incorporating the complex electrical
      properties of myocardium to identify the muscle component in the measurement and
      by including the transient nature of the field non uniformity. Cardiac muscle is
      unique in that the permittivity is high enough at audio frequencies to make the
      muscle component of the signal identifiable in the imaginary part of an
      admittance measurement. The muscle contribution can thus be uniquely identified
      and removed from the combined muscle - blood measurement. In general, both error
      sources are transient and are best removed in real time as data are collected.
      This paper reviews error correction methods and establishes that the relative
      magnitudes of the error concerns are different in small and large hearts.

PMID- 21097043
TI  - Acoustical screening for obstructive sleep apnea during wakefulness.
AB  - In this paper a new non-invasive method for screening patients with obstructive
      sleep apnea (OSA) during wakefulness is proposed. Eight people with OSA and eight
      non-apneic individuals participated in this study. The tracheal breath sound was
      recorded in supine and upright positions during both nose and mouth breathing
      maneuvers. Spectral analysis of the respiratory sound signals showed the
      variation in the average power of the sounds at different positions to be a
      characteristic feature discriminating the two groups. Using this feature, the OSA
      and non-apneic participants were classified by quadratic discriminant analysis
      (QDA). The specificity, sensitivity, and classification accuracy of the
      classifier were found to be 100%, 87.5%, and 95.75%, respectively. These results
      are encouraging for the use of the proposed method as a fast, simple and
      screening tool for diagnosis of OSA during wakefulness.

PMID- 21097044
TI  - Unsupervised classification of respiratory sound signal into snore/no-snore
      classes.
AB  - In this study, an automatic and online snore detection algorithm is proposed. The
      respiratory sound signals were recorded simultaneously with Polysomnography (PSG)
      data during sleep from 20 patients (10 simple snorers and 10 OSA patients). The
      sound signals were recorded by two tracheal and ambient microphones. The
      potential snoring episodes were identified using Vertical Box (V-Box) algorithm.
      The normalized 500Hz sub-band energy features of each episode were calculated.
      Principal component analysis (PCA) was applied to a 10-dimensional feature space
      to reduce it to a new 2-dimensional feature space. An unsupervised K-means
      clustering algorithm was then deployed to label the sound episodes as either
      snore or no-snore class. The performance of the algorithm was evaluated using
      manual annotation of the sound signals. The overall accuracy of the system was
      found to be 98.2% for the tracheal recordings and 95.5% for the sounds recorded
      by the ambient microphone.

PMID- 21097045
TI  - Acoustic mapping of the lung based on source localization of adventitious
      respiratory sound components.
AB  - The aim of this study is to devise a methodology to estimate and depict the
      source locations of respiratory adventitious sound components in the lungs,
      particularly crackles, associated with certain pulmonary diseases. Using the
      multichannel respiratory sound signals recorded on the chest wall, we have tried
      to locate the sources of crackling sounds. The source localization is performed
      using basic independent component analysis (basic ICA) followed by an evaluation
      of the mixing coefficients in a center of weights approach, where after the ICA,
      by taking the relevant mixing matrix coefficients and assuming them to be placed
      on the microphone locations, the estimated sound source location is calculated as
      the center of those weights. In order to select both the proper data segments
      prior to the ICA, and the relevant independent component (IC) among the source
      signal estimates of the ICA subsequently, a Bayesian classifier (under the
      assumption of Gaussian likelihoods) has been trained, using the data of the same
      subject yet a different acquisition session from the one intended for source
      localization. The outcome of the algorithm is a map of estimated source locations
      of crackles with respect to the microphone locations, which is presented together
      with the error performances (both validation and test) of the classifier. This
      approach for the estimation and mapping of the adventitious sound source
      locations in the lungs using the acoustic data may be a promising imaging
      alternative, which is practical, non-expensive and harmless.

PMID- 21097046
TI  - Abnormal pattern detection in Wireless Capsule Endoscopy images using nonlinear
      analysis in RGB color space.
AB  - In recent years, an innovative method has been developed for the non-invasive
      observation of the gastrointestinal tract (GT), namely Wireless Capsule Endoscopy
      (WCE). WCE especially enables a detailed inspection of the entire small bowel and
      identification of its clinical lesions. However, the foremost disadvantage of
      this technological breakthrough is the time consuming task of reviewing the vast
      amount of images produced. To address this, a novel technique for distinguishing
      pathogenic endoscopic images related to ulcer, the most common disease of GT, is
      presented here. Towards this direction, the Bidimensional Ensemble Empirical Mode
      Decomposition was applied to RGB color images of the small bowel acquired by a
      WCE system in order to extract their Intrinsic Mode Functions (IMFs). The IMFs
      reveal differences in structure from their finest to their coarsest scale,
      providing a new analysis domain. Additionally, lacunarity analysis was employed
      as a method to quantify and extract the texture patterns of the ulcer regions and
      the normal mucosa, respectively, in order to discriminate the abnormal from the
      normal images. Experimental results demonstrated promising classification
      accuracy (>95%), exhibiting a high potential towards WCE-based analysis.

PMID- 21097047
TI  - Classification of elderly as fallers and non-fallers using Centre of Pressure
      velocity.
AB  - Falls are a leading cause of death in the elderly. One of the most common methods
      of predicting falls is to evaluate balance using force plate measurement of the
      Centre of Pressure (COP) displacement. This signal, known as a stabilogram, can
      be decomposed into movement in anteroposterior (AP) and mediolateral (ML)
      directions. It has been suggested that studying the velocity of COP displacement
      could lead to new insights into fall risk. The aim of this study was to attempt
      to classify elderly fallers and non-fallers, as well as control subjects based on
      COP velocity measurements. Three groups of 10 subjects (controls, elderly
      fallers, and elderly non-fallers) were compared. Discriminant function analysis
      was able to correctly classify 90% of the subjects based only on COP velocity
      measurements. Further work is needed to determine whether this parameter might be
      of use in longitudinal measurement of fall risk in home-dwelling elderly.

PMID- 21097048
TI  - Graph-based methodology for the kinematic synthesis of wearable assistive robots
      for the lower limbs.
AB  - Non-anthropomorphic wearable robots (WRs) give good grounds for expecting
      advantageous performances over traditional anthropomorphic solutions from both
      the standpoints of ergonomics and of the dynamical interaction with the human
      body.

PMID- 21097049
TI  - RUPERT closed loop control design.
AB  - Robot-assisted rehabilitation is an active area of research in the field of
      stroke rehabilitation. RUPERT is a wearable robotic exoskeleton powered by
      pneumatic muscle actuators. In this study, we described the structure of the
      controllers for the five degrees of freedom currently used by RUPERT. We applied
      the RUPERT on 6 stroke patients to provide robot-assisted rehabilitation therapy
      in a clinical study. Statistical chi(2) test on the proportion of successfully
      reaching targets showed that 3 out of the 6 patients demonstrated significant
      improvement in reaching targets successfully, and the remaining 3 did not show
      performance improvement or deterioration. We plan to implement the RUPERT in the
      patient's house for easier access and more frequent use. More significant
      performance results are expected.

PMID- 21097050
TI  - 3D handheld laser scanner based approach for automatic identification and
      localization of EEG sensors.
AB  - This paper describes and assesses for the first time the use of a handheld 3D
      laser scanner for scalp EEG sensor localization and co-registration with magnetic
      resonance images. Study on five subjects showed that the scanner had an
      equivalent accuracy, a better repeatability, and was faster than the reference
      electromagnetic digitizer. According to electrical source imaging, somatosensory
      evoked potentials experiments validated its ability to give precise sensor
      localization. With our automatic labeling method, the data provided by the
      scanner could be directly introduced in the source localization studies.

PMID- 21097051
TI  - A non rigid registration and deformation algorithm for ultrasound & MR images to
      guide prostate cancer therapies.
AB  - Multimodality image registration is a critical issue in image-guided cancer
      ablation techniques. Focal therapies of prostate cancer are usually monitored
      using ultrasound imaging, while the dose planning is performed on MRI. In this
      study, a new multimodality images registration and deformation method, based on
      the Thin Plate Splines -Rigid Point Matching (TPS-RPM) algorithm, is introduced.
      The Method combines non-rigid mapping and interpolation to deform the images.
      Preliminary results obtained on phantom and clinical images showed that the
      registration is accurate and robust against landmarks initialization.

PMID- 21097052
TI  - 2D/3D registration for X-ray guided bronchoscopy using distance map
      classification.
AB  - In X-ray guided bronchoscopy of peripheral pulmonary lesions, airways and nodules
      are hardly visible in X-ray images. Transbronchial biopsy of peripheral lesions
      is often carried out blindly, resulting in degraded diagnostic yield. One
      solution of this problem is to superimpose the lesions and airways segmented from
      preoperative 3D CT images onto 2D X-ray images. A feature-based 2D/3D
      registration method is proposed for the image fusion between the datasets of the
      two imaging modalities. Two stereo X-ray images are used in the algorithm to
      improve the accuracy and robustness of the registration. The algorithm extracts
      the edge features of the bony structures from both CT and X-ray images. The edge
      points from the X-ray images are categorized into eight groups based on the
      orientation information of their image gradients. An orientation dependent
      Euclidean distance map is generated for each group of X-ray feature points. The
      distance map is then applied to the edge points of the projected CT images whose
      gradient orientations are compatible with the distance map. The CT and X-ray
      images are registered by matching the boundaries of the projected CT
      segmentations to the closest edges of the X-ray images after the orientation
      constraint is satisfied. Phantom and clinical studies were carried out to
      validate the algorithm's performance, showing a registration accuracy of 4.19(+/-
      0.5) mm with 48.39(+/- 9.6) seconds registration time. The algorithm was also
      evaluated on clinical data, showing promising registration accuracy and
      robustness.

PMID- 21097053
TI  - Wearable shoe-based device for rehabilitation of stroke patients.
AB  - Regaining the ability to walk after a stroke is a major rehabilitation goal.
      Rehabilitation strategies that are task oriented and intensive can drive cortical
      reorganization and increase activity levels in people after a stroke. This paper
      describes a novel, wearable device for use with such rehabilitation strategies.
      The device is based on the combination of a smartphone and in-shoe sensors, and
      is designed to operate in free living conditions. Data collected from the device
      can be used for automatic recognition of postures and activities,
      characterization of extremity use and to provide behavioral enhancing feedback to
      patients recovering from a stroke. The proposed wearable platform's operation was
      validated in a small scale study involving three healthy individuals. The average
      accuracy of classification of three postures and activities was over 99%. Based
      on the results of validation and previously reported results on recognition of
      postures and activities in stroke patients, it is anticipated that recognition of
      postures and activities may be performed with high accuracy in free living
      conditions.

PMID- 21097054
TI  - Poly(N-isopropylacrylamide) beads synthesis with nanoparticles embedded for the
      implementation of shrinkable medical microrobots for biomedical applications.
AB  - This paper describes the synthesis of thermoresponsive hydrogel bead for the
      implementation of untethered medical microrobots and other microdevices. These
      entities will have magnetic nanoparticles embedded, and will be targeted inside
      the body with an adapted Magnetic Resonance Imaging (MRI) system, and then
      triggered by the application of an alternating magnetic field for various
      functions, including but not limited to drug delivery and release. A method is
      presented here to synthesize PNIPA particles, within alginate mold, which can be
      dissolved when hydrogel is completely polymerized and particles with diameter
      around 1mm are synthesized, with possibility of reducing the size with an
      electrostatic fields. Interesting volume losses has been recorded, depending of
      the crosslinker concentration. Hydrogel with nanoparticles embedded has also been
      synthesized, without affecting the polymerization, and with no significant effect
      on the volume change. Finally, transition temperature has been increase over the
      body temperature by copolymerization with acrylic acid.

PMID- 21097055
TI  - The influence of surface properties of plasma-etched polydimethylsiloxane (PDMS)
      on cell growth and morphology.
AB  - Polydimethylsiloxane (PDMS) or silicone rubber is a widely used implant material.
      Approaches to promote tissue integration to PDMS are desirable to avoid clinical
      problems associated with sliding and friction between tissue and implant. Plasma
      etching is a useful way to control cell behavior on PDMS without additional
      coatings. In this work, different plasma processing conditions were used to
      modify the surface properties of PDMS substrates. Surface nanotopography and
      wettability were measured to study their effect on in vitro growth and morphology
      of fibroblasts. While fluorinated plasma treatments produced nanorough
      hydrophobic and superhydrophobic surfaces that had negative or little influences
      on cellular behavior, water vapor/oxygen plasma produced smooth hydrophillic
      surfaces that enhanced cell growth.

PMID- 21097056
TI  - Geometric order in proliferating epithelia: impact of rearrangements and cleavage
      plane orientation.
AB  - Regulation of proliferation is required for normal development of tissues and
      prevention of cancer formation. Continuous control of proliferation leads to
      regular shaped cells forming characteristic tissue patterns. Epithelial tissues
      serve as a model system for studying tissue morphogenesis. Several groups have
      studied epithelial morphogenesis using topological or geometric models, with
      various assumptions. In this study, we have developed a method to simulate the
      dynamic process of proliferating epithelia using an off-lattice cellular model.
      Our method realistically models the shape, size, geometry, lineage, cleavage
      plane orientation as well as topological properties of individual cells. We find
      that cellular rearrangements and cleavage plane orientation are critical in the
      formation of the observed cellular pattern of epithelia, including a high
      percentage of hexagons in proliferating epithelial cells. It is likely that the
      rearrangements and orientation of the cleavage plane reduces the overall stress
      on the cell. We show that a high percentage of hexagons in proliferating
      epithelia can be obtained using uniform growth rates, which was considered
      unlikely in previous studies. Our off-lattice cellular model provides an
      improvement over existing topological for studying the dynamics of proliferating
      epithelium.

PMID- 21097057
TI  - Combinations of hydrostatic pressure and shear stress influence morphology and
      adhesion molecules in cultured endothelial cells.
AB  - Endothelial cells are exposed to mechanical stimuli from blood flow and blood
      pressure. However, it is not yet fully understood how their simultaneous exposure
      affects endothelial function. Firstly, in this study we investigated the effect
      of combined stress on morphology of cultured human aortic endothelial cells
      (HAECs). In the results, HAECs exposed to steady flow (a pressure of 100 mmHg,
      and a shear stress of 1.5 Pa) were more elongated than those exposed to a
      hydrostatic pressure of 100 mmHg and HAECs exposed to pulsatile flow (a pressure
      of 80/120 mmHg, and a shear stress of 1.2/1.8 Pa) were more elongated than those
      exposed to steady flow. Similarly, HAECs exposed to pulsatile flow were most
      oriented to the flow direction among these three stresses. Secondly, we
      investigated the effect of combined stress on gene expression of cell adhesion
      molecules in HAECs. After stress exposure to HAECs the mRNA of intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E
      selectin were measured by real time RT-PCR. In the results, the exposure of
      steady flow increased the mRNA levels of ICAM-1 compared to the exposure of
      hydrostatic pressure; however, the exposure of pulsatile flow decreased the mRNA
      level of ICAM-1 compared to the exposure of steady flow. These findings suggest
      that gene expression of cell adhesion molecules induced by combined stress were
      different to the superposition of individual stress and that not only difference
      in the components of combined stress but also difference in the magnitude of the
      components of combined stress are important.

PMID- 21097058
TI  - Modeling the effects of nanoparticles on neuronal cells: from ionic channels to
      network dynamics.
AB  - Engineered nanoparticles (NPs) offer great application potential in various
      fields, for example the chemical industry, energy management or medical sciences.
      Nanoparticles are increasingly being incorporated into daily products. But what
      happens, if living organisms are exposed to those NPs? Their ability to move
      seemingly barrier-free in organic tissue could be both beneficial and harmful.
      Even though research concerning nanotoxicity has already begun, there are still
      many open questions to be addressed. In this report, we propose a computational
      model applying the steady-state Hodgkin-Huxley-equations and the Differential
      Evolution Algorithm for fitting the model to the data of patch-clamp measurements
      carried out by our group: Coated silvernanoparticles (Ag-Nano) in different
      concentrations were applied to single chromaffin cells while measuring the ionic
      currents in the whole-cell configuration. Compared to controls, significant
      differences in sodium-currents were observed after the application of NPs. Using
      the computational model, we could evaluate the parameters which model the change
      in behavior of neuronal cells due to the addition of Ag-Nano. This can ultimately
      give insight to underlying mechanisms. An integration to model the dynamic
      behavior of neuronal networks exposed to NP is easily conceivable using this
      technique.

PMID- 21097059
TI  - The development of a new computational model for the electromechanics of the
      human ventricular myocyte.
AB  - In this work we present a new electromechanical cardiac myocyte model tailored to
      reproduce the electrical and force generating activities of human ventricular
      myocytes. The model was created by coupling two existing models: the ten Tusscher
      electrophysiology model and the Rice myofilament mechanics model. The parameters
      of the new model were adjusted in order to replicate the available experimental
      data for human myocytes. The main challenges in this work were the strong
      feedbacks between the models, the high non-linearity of the models and mainly the
      lack of human data to make the adjustments.

PMID- 21097060
TI  - Developing IEEE medical device standards: a case study, wearable cuffless blood
      pressure measuring devices.
AB  - The Institute of Electrical and Electronics Engineers Standards Association (IEEE
      SA) is a leading standards developing organization of global industry standards
      in a wide-range of industries, including biomedical and healthcare.

PMID- 21097061
TI  - Mining terabytes of submillimeter-resolution ECoG datasets for neurophysiologic
      biomarkers.
AB  - Recent research in brain-machine interfaces and devices to treat neurological
      disease indicate that important network activity exists at temporal and spatial
      scales beyond the resolution of existing implantable devices. We present
      innovations in both hardware and software that allow sampling and interpretation
      of data from brain networks from hundreds or thousands of sensors at
      submillimeter resolution. These innovations consist of novel flexible, active
      electrode arrays and unsupervised algorithms for detecting and classifying
      neurophysiologic biomarkers, specifically high frequency oscillations. We propose
      these innovations as the foundation for a new generation of closed loop
      diagnostic and therapeutic medical devices, and brain-machine interfaces.

PMID- 21097062
TI  - Classification of spoken words using surface local field potentials.
AB  - Cortical surface potentials recorded by electrocorticography (ECoG) have enabled
      robust motor classification algorithms in large part because of the close
      proximity of the electrodes to the cortical surface. However, standard clinical
      ECoG electrodes are large in both diameter and spacing relative to the underlying
      cortical column architecture in which groups of neurons process similar types of
      stimuli. The potential for surface micro-electrodes closely spaced together to
      provide even higher fidelity in recording surface field potentials has been a
      topic of recent interest in the neural prosthetic community. This study describes
      the classification of spoken words from surface local field potentials (LFPs)
      recorded using grids of subdural, nonpenetrating high impedance micro-electrodes.
      Data recorded from these micro-ECoG electrodes supported accurate and rapid
      classification. Furthermore, electrodes spaced millimeters apart demonstrated
      varying classification characteristics, suggesting that cortical surface LFPs may
      be recorded with high temporal and spatial resolution to enable even more robust
      algorithms for motor classification.

PMID- 21097063
TI  - Performance assessment on different measurement positions for monitoring HR/RR
      during sleep.
AB  - This study aims to investigate the measurement performance on different sensor
      deployment and to determine the optimal position for monitoring heart rate (HR)
      and respiration rate (RR) during sleep. Five identical sensor boards were
      deployed on different positions simultaneously during sleep to detect changes of
      applied pressure due to heart beating and breathing. One board was set beneath
      the pillow; the other four boards were set under the mattress aligning with the
      head, back, hip and calf, respectively. Data were collected from five healthy
      subjects during a 2-hour's nap individually. Detection performance was evaluated
      by sensitivity and positive predictivity. The results showed that nearly all of
      the positions could be used to detect heart rate; both sensitivity and positive
      predictivity were over 85% among five persons. All of the positions could be used
      to detect respiration rate except for calf. The highest performance of
      sensitivity and positive predictivity in respiration rate detection could be
      found in the hip position, which reached as high as 99%. The optimal position
      with overall best performance for HR and RR measurement is considered in the hip.

PMID- 21097064
TI  - Multimodal localization in the context of a medical telemonitoring system.
AB  - This paper addresses a localization system which is based on a combination of
      information from two modalities: a Smart Home Person Tracking (SHPT) composed of
      infrared sensors and an Audio Person Tracking (APT) which uses microphones able
      to estimate azimuth of acoustic sources. This combination improves precision of
      localization compared to a standalone or separated module. The localization
      software facilitates the integration of both SHPT and APT systems, to display the
      position in real time, to record data and detect some distress situations (some
      kind of fall). Results on implementation show good adaptation for Smart Home
      environments and a robust detection.

PMID- 21097065
TI  - SAR evaluations of mobile phone close to a pacemaker implanted in human body.
AB  - Recently, electromagnetic interference (EMI) of an implanted pacemaker with a
      mobile phone was largely investigated. As for the pacemaker, the Japan National
      Authorities have recommended to keep the mobile phone in safe distance from the
      cardiac pacemaker. Meanwhile, evaluation of the interaction between the
      electromagnetic (EM) wave and human body was in progress. Therefore, the
      absorption of EM energy to the human body especially around the pacemaker, where
      the mobile phone was in a chest pocket of the pacemaker holder, was thoroughly
      evaluated. We provided the calculation of specific absorption rate (SAR)
      distributions around the pacemaker model that implanted into a rectangular
      parallelepiped torso model, when a mobile phone model is placed in the vicinity.
      In addition, the SAR was also experimentally performed to validate the such
      numerical calculations. We confirmed that SAR distributions could be estimated
      from the presence or absence of pacemaker model. Moreover, the measurement
      results of the SAR distribution suited to the calculation, thus its validation
      was achieved.

PMID- 21097066
TI  - A system to promote self-behaviors of patients with coronary heart disease.
AB  - Personalized health devices are the novel paradigm to reduce healthcare costs and
      to improve the quality of health services. At the same time, health interventions
      and promotion of self behaviors generate benefits to healthcare and allow
      citizens to be more involved in their own health management. This paper describes
      the process followed in HeartCycle project to design education and coaching
      services to promote self-behaviors in a closed loop monitoring system for
      patients with coronary heart diseases that suffered a myocardial infarction.

PMID- 21097067
TI  - Implementation of an iPhone as a wireless accelerometer for quantifying gait
      characteristics.
AB  - The capacity to quantify and evaluate gait beyond the general confines of a
      clinical environment under effectively autonomous conditions may alleviate
      rampant strain on limited and highly specialized medical resources. An iPhone
      consists of a three dimensional accelerometer subsystem with highly robust and
      scalable software applications. With the synthesis of the integral iPhone
      features, an iPhone application, which constitutes a wireless accelerometer
      system for gait quantification and analysis, has been tested and evaluated in an
      autonomous environment. The acquired gait cycle data was transmitted wireless and
      through email for subsequent post-processing in a location remote to the location
      where the experiment was conducted. The iPhone application functioning as a
      wireless accelerometer for the acquisition of gait characteristics has
      demonstrated sufficient accuracy and consistency.

PMID- 21097068
TI  - From pain to stress evaluation using heart rate variability analysis: development
      of an evaluation platform.
AB  - Heart Rate Variability analysis has been shown in several studies to measure the
      Autonomic Nervous System tone, which is strongly influenced by pain, stress or
      anxiety. We have previously described and developed an Analgesia/Nociception
      Index for pain measurement during surgical procedure. This index based on a heart
      rate variability analysis can be considered as a vagal tone index and used in
      several other environments. In this paper, we present an adaptation of our
      technology for stress / anxiety evaluation in the particular domain of incident
      management teams training.

PMID- 21097069
TI  - A basic study for patch type ambulatory 3-electrode ECG monitoring system for the
      analysis of acceleration signal and the limb leads and augmented unipolar limb
      leads signal.
AB  - A compact and portable device was designed for preliminary study of patch type
      ambulatory 3-electrode ECG monitoring system for limb leads and augmented
      unipolar limb leads signal analysis. The developed system also can measure and
      send the acceleration signals wirelessly during daily life to analyze the user's
      information. The 3-electrode system is feasible to provide the information of
      limb leads and augmented unipolar limb leads for further arrhythmia analysis and
      simultaneously shows lots of issues to be more broadly applicable and more
      powerful device.

PMID- 21097070
TI  - Biomedical signals monitoring based in mobile computing.
AB  - The main objective of this project consists in the development of a biomedical
      instrumentation prototype for acquisition, processing and transmission of
      biomedical signals. These biomedical signals are acquired and then processed with
      a microcontroller. After processing, all data are sent to a communication
      interface that can send this information to a personal computer or a cell phone.
      The prototype developed, which is a digital blood pressure meter, is intended to
      allow remote monitoring of patients living in areas with limited access to
      medical assistance or scarce clinical resources. We believe that this development
      could be helpful to improve people's quality of life, as well as to allow an
      improvement in the government attendance indices.

PMID- 21097071
TI  - Modeling the human body shape in bioimpedance vector measurements.
AB  - Human body shape, called somatotype, has described physique of humans in health
      and sports applications, relating anthropometric measurements to fatness,
      muscularity and linearity in a structured way. Here we propose a new method based
      on bioelectric impedance vector analysis (BIVA) of R/H and Xc/H to represent the
      cross-sectional area and the body cell mass in a given surface area (m(2))
      respectively. Data from six gymnasts, ten dancers, and five fashion models,
      groups whose physiques and BMI ranges were distinct from one another, were
      measured for somatotype and BIVA. The models had highest values of the R/H and
      gymnasts the lowest. Xc/H was lower in models than in the dancers and gymnasts (p
      < 0.05). Phase angle was lowest in the models and highest in gymnasts
      significantly (p < 0.05). Pattern analysis from BIVA corresponded to the
      calculated anthropometric somatotype supporting the hypothesis that BIA's
      resistance (R) and reactance (Xc) are meaningful discriminates of body size and
      function which relate to physique in a purposive way.

PMID- 21097072
TI  - iWander: An Android application for dementia patients.
AB  - Non-pharmacological management of dementia puts a burden on those who are taking
      care of a patient that suffer from this chronic condition. Caregivers frequently
      need to assist their patients with activities of daily living. However, they are
      also encouraged to promote functional independence. With the use of a discrete
      monitoring device, functional independence is increased among dementia patients
      while decreasing the stress put on caregivers. This paper describes a tool which
      improves the quality of treatment for dementia patients using mobile
      applications. Our application, iWander, runs on several Android based devices
      with GPS and communication capabilities. This allows for caregivers to cost
      effectively monitor their patients remotely. The data uncollected from the device
      is evaluated using Bayesian network techniques which estimate the probability of
      wandering behavior. Upon evaluation several courses of action can be taken based
      on the situation's severity, dynamic settings and probability. These actions
      include issuing audible prompts to the patient, offering directions to navigate
      them home, sending notifications to the caregiver containing the location of the
      patient, establishing a line of communication between the patient-caregiver and
      performing a party call between the caregiver-patient and patient's local 911. As
      patients use this monitoring system more, it will better learn and identify
      normal behavioral patterns which increases the accuracy of the Bayesian network
      for all patients. Normal behavior classifications are also used to alert the
      caregiver or help patients navigate home if they begin to wander while driving
      allowing for functional independence.

PMID- 21097073
TI  - Mult-I/O - a middleware multi input and output for access devices: a case study
      applied the biomedical devices.
AB  - The great diversity in the architecture of hardware devices allied to many
      communication protocols, has been hindering the implementation of systems that
      need to access these devices. Given these differences, it appears the need of
      providing the access of these devices in a transparent way. In this sense, the
      present work proposes a middleware, mult input and output for access the devices,
      as a way of abstracting the writing and reading data mechanisms in hardware
      devices, contributing this way, for increasing systems productivity, as the
      developers are just focused in their functional requirements.

PMID- 21097074
TI  - Differences in the laboratory parameters of obese and healthy Hungarian children
      and their use in automatic classification.
AB  - Obesity is a rapidly spreading endemic in almost every country of the developed
      world, of which Hungary is no exception. By a joint research project we aim to
      deepen our understanding of obesity-associated, and especially obesity-predicting
      changes of clinical markers (anthropometric indices, body composition, laboratory
      results etc.) in children, especially in teenage population. This paper presents
      the preliminary results of our investigations which pertain to obesity-related
      alterations in routine blood test parameters. For that end, we examined 340
      healthy and obese children. Results show that there are differences between the
      routine laboratory parameters of obese and healthy subjects that are both
      statistically significant and medically interesting. We point out these
      differences in a statistically precise way, and show a method which can be
      efficiently used to classify children based on their laboratory parameters. This
      result can be used later to develop a more realistic model to predict the risk of
      obesity.

PMID- 21097075
TI  - Statewide validation of a patient admissions prediction tool.
AB  - We validate a proprietary system to predict hospital emergency department
      presentations. A key advantage in planning health service delivery requirements
      and catering for the large numbers of people presenting to hospitals is the
      ability to predict their numbers. Year-ahead forecasts of daily hospital
      presentations were generated for 27 public hospitals in Queensland, Australia
      from five years of historic data. Forecast accuracy was assessed by calculating
      the Mean Absolute Percentage Error and Root Mean Squared Error between
      predictions and observed admissions. Emergency Department presentations were
      found to be not random and can be predicted with an accuracy of around 90%.
      Highest accuracy was over weekends and summer months, and Public Holidays had the
      greatest variance in forecast accuracy. Forecasts for urban facilities were
      generally more accurate than regional (accuracy is related to sample size).

PMID- 21097076
TI  - Embedding patients confidential data in ECG signal for healthcare information
      systems.
AB  - In Wireless tele-cardiology applications, ECG signal is widely used to monitor
      cardiac activities of patients. Accordingly, in most e-health applications, ECG
      signals need to be combined with patient confidential information. Data hiding
      and watermarking techniques can play a crucial role in ECG wireless tele
      monitoring systems by combining the confidential information with the ECG signal
      since digital ECG data is huge enough to act as host to carry tiny amount of
      additional secret data. In this paper, a new steganography technique is proposed
      that helps embed confidential information of patients into specific locations
      (called special range numbers) of digital ECG host signal that will cause minimal
      distortion to ECG, and at the same time, any secret information embedded is
      completely extractable. We show that there are 2.1475 * 10(9) possible special
      range numbers making it extremely difficult for intruders to identify locations
      of secret bits. Experiments show that percentage residual difference (PRD) of
      watermarked ECGs can be as low as 0.0247% and 0.0678% for normal and abnormal ECG
      segments (taken from MIT-BIH Arrhythmia database) respectively.

PMID- 21097077
TI  - A pilot study to examine the relationship of 3D pain drawings with objective
      measures in mobility impaired people suffering from low back-pain.
AB  - Over the years, an increasing number of the adult population suffers from some
      form of back pain during their lifetime, something that consecutively has a very
      important impact on a country's health, as well as economic systems. It is beyond
      dispute though, that pain is a feeling or emotion that is subjective in nature.
      Thus, traditional methods of measuring pain are consequently considered to be
      subjective in their ability to efficiently gather and communicate such pain
      measurements. As a result, the work presented in this paper attempts to address
      the aforementioned limitation by presenting a theoretical framework, in which
      back pain measurements are taken, and the hypothetical association with objective
      measures, performed with the upcoming technique of pressure mapping, are
      indicated. A pilot study on wheelchair users to examine our proposed framework
      was conducted, with results of this pilot study showing that it is a promising
      solution for the purpose intended, and that it could generally prove to be a
      significant complementary method for the back pain community.

PMID- 21097078
TI  - Custom HL7 V3 message provider using web services security features.
AB  - Due the availability of new data transmission technologies and new standards for
      medical studies development, e-health systems have had a sustained adoption in
      recent years. In this scenario, the health systems are incorporating and
      increasing the health services offering in response to their needs. This paper
      presents a system able to transmit medical studies using different communication
      channels providing an effective use of the medical equipment, the data
      transmission networks and the human resources availability. This system is based
      on service oriented architecture (SOA) to propose different alternatives in terms
      of which data needs to be transmitted for the acquired medical study, in order to
      attend different medical diagnosis providing an efficient use of the available
      communication channels. About the security implemented for the data transmission,
      there are different configurations available for encryption and signing at
      message level, to ensure that messages cannot be changed without detection during
      the transmission. For message definition, the HL7 V3 standard is implemented and
      the medical studies are stored in a centralized database located in a web server
      accessible via Internet to enable second medical opinion from other specialists.

PMID- 21097079
TI  - Web-based healthcare hand drawing management system.
AB  - The paper addresses Medical Hand Drawing Management System architecture and
      implementation. In the system, we developed four modules: hand drawing management
      module; patient medical records query module; hand drawing editing and upload
      module; hand drawing query module. The system adapts windows-based applications
      and encompasses web pages by ASP.NET hosting mechanism under web services
      platforms. The hand drawings implemented as files are stored in a FTP server. The
      file names with associated data, e.g. patient identification, drawing physician,
      access rights, etc. are reposited in a database. The modules can be conveniently
      embedded, integrated into any system. Therefore, the system possesses the hand
      drawing features to support daily medical operations, effectively improve
      healthcare qualities as well. Moreover, the system includes the printing
      capability to achieve a complete, computerized medical document process. In
      summary, the system allows web-based applications to facilitate the graphic
      processes for healthcare operations.

PMID- 21097080
TI  - Secondary use of EHR data for correlated comorbidity prevalence estimate.
AB  - Comorbidity is quite common in the medical practice. In this article we explore a
      way to use anonymized Electronic Health Records (EHR) data in order to derive
      correlations, evidence based likelihood of comorbidities manifestation within the
      EHR patients population. The ultimate goal is to present the information to the
      health care provider at the moment when a new diagnosis is entered for the
      patient, thus increasing health care provider's attention to possible problems,
      even if they are at sub-clinical or asymptomatic stage.

PMID- 21097081
TI  - Standardization proposal to pharmaceutical compounded forms elaboration -
      information system.
AB  - Quality is fundamental during compounded preparations. In spite of this, there is
      not standardization for compounding formulations preparation. Nowadays, there are
      some information systems to compounding pharmacy area, however they don't offer
      functions related to the compounding elaboration. Standardization is essential to
      systems success. The goal of this paper was to propose a standard to
      pharmaceutical semisolid and liquid external use forms preparation. First was
      performed a study to check the characteristics on drug preparation at different
      establishments. Then, a standardization proposal was specified represented by
      flowcharts, including sequence, features and drug elaboration restrictions.
      Relevant variables were also identified and defined. Active's name, pH and
      compatibilities are some examples. Flowcharts cover prescription analysis,
      actives compatibility verification, solubility, pharmaceutical incipient addition
      and other aspects that are important considering drug preparation. These
      flowcharts were validated by compounding pharmacy specialists applying Delphi
      Method. An Information System to support compounding pharmacist's decision and
      help actives selection was developed, using the standard proposed, and the
      defined variables as knowledge base. Six common medical prescriptions, generally
      elaborated with wrong characteristics were used to evaluate the system. To all of
      them, the system offered a correct action plan to drug elaboration.

PMID- 21097082
TI  - A new paradigm for telehealth implementation.
AB  - Recently, efforts have been made to treat patients at home as much as possible.
      In many cases, the reason for the patient staying in hospital is not that he/she
      actually needs active medical care. Often, the principal reason for a lengthy
      stay in hospital is simply continual observation. This paper explains our
      experience and strategy to support the treatment of patients in their own home
      through the remote monitoring of physiological signals. The benefits of such
      remote monitoring are wide-ranging; the patient can continue to live their normal
      life, their risk of infection is reduced, costs are significantly decreased for
      the hospital, and clinician time is utilised more effectively.

PMID- 21097083
TI  - Building an information security strategy for EHR: guidelines for assessing the
      current situation.
AB  - This paper is looking at electronic health record (EHR) systems and their
      information security strategy. It focuses on the first step of building an
      information security strategy which is analysing the current situation of an EHR
      system. This research is based on different research methods applied to different
      EHR systems. In this paper we define eight elements that can be used as
      guidelines for how best to assess the current situation of any EHR system.

PMID- 21097084
TI  - Young's modulus measurement of the porcine ligamentum flavum for evaluating the
      deformation during epidural insertion.
AB  - In order to check validity of the porcine ligamentum flavum as a substitute of
      human tissue for evaluating the epidural needles, the thickness and the Young's
      modulus were measured, and a finite element analysis was carried out. Twenty-four
      specimens were stained by the Elastica-van Gieson method. The average value of
      the thickness was 1.2 mm. The tensile tester was employed for measuring the
      Young's modulus. A cross sectional area was obtained by X-ray CT image. Young's
      modulus was 1.6 MPa. The measured properties of a porcine ligamentum flavum
      showed a reduced thickness and smaller Young's modulus than the human ligamentum
      flavum. On a finite element analysis, the shape of the ligamentum flavum was
      modeled as a square plate 5 mm in width and 5 mm in depth. The thickness and the
      Young's modulus were set at the measured value for a porcine model, and value
      from the literature for a human model. For simplicity, a constant load of 10 N
      was applied at the center of each model. The porcine model exhibited deformation
      1.7 times that of the human model.

PMID- 21097085
TI  - Finite element model of a greater trochanteric reattachment system.
AB  - Detachment of greater trochanter (GT) is generally associated with hip
      arthroplasty complications and needs for repositioning and fixation. A new GT
      reattachment system (Y3) was proposed to reduce GT displacements in anterior
      posterior direction to decrease non-union issues. The goal of this study is to
      develop and validate a FEM of the Y3 GTR system. FEM validation suggests a good
      concordance between numerical and experimental GT displacements. Sensitivity
      study show that the transition between proximal and distal branches of Y3 design
      is the most influent part on all GT displacements. The anterior branch affects
      more anterior-posterior displacements and rotation while the posterior branch
      affects more proximal displacements and rotation. This study provides an improved
      understanding of the influence of Y3 geometry on GT displacements.

PMID- 21097086
TI  - Finite element analysis of an acetabular trial implant.
AB  - A variable diameter trial liner (VDTL) was designed to reduce the costs related
      to cleaning, sterilisation and storage of surgical instruments used for total hip
      arthroplasty. The purpose of this study was to develop a finite element model to
      evaluate the mechanical behavior of the VDTL before manufacturing of a functional
      prototype. The finite element analysis consists to identify the maximum stresses
      applied on the VDTL and compare these values to the yield strength of stainless
      steel 17-4 (540 MPa) to asses if the VDTL will resist to loading conditions
      similar to the ones occurring during the surgical procedure. The results
      demonstrated the need to improve the mechanical strength of the current concept
      of the VDTL. These results will serve as indications for upcoming design
      refinements.

PMID- 21097087
TI  - The shape of the acetabular cartilage surface and its role in hip joint contact
      stress.
AB  - The acetabular cartilage is normally represented as a spherical shape in
      orthopedic clinic and related researches. The aim of the study was to present a
      new mathematic representation with better fit to the acetabular cartilage surface
      and to investigate the role of its shape on the hip joint contact stress.

PMID- 21097088
TI  - In vitro kinematic measurements of the patellar tendon in two different types of
      posterior-stabilized total knee arthroplasties.
AB  - BACKGROUND: Fixed-bearing posterior-stabilized (PS) total knee arthroplasty (TKA)
      has been used in Asian countries for several years, but few studies have
      investigated differences in the kinematic properties of the patellar tendon after
      standard PS TKA as compared to high-flex PS TKA. PURPOSE: To quantify the in
      vitro three-dimensional (3D) kinematics of the patellar tendon during passive
      high flexion and full extension before and after two different types of PS TKAs.
      METHODS: Six fresh-frozen cadaveric knees were tested under the following
      conditions: the unaltered state, status-post traditional PS prostheses (Simth
      nephew GENESIS II) replacement, and status-post high-flexion PS prostheses
      replacement. The soft tissue around the knee and the quadriceps muscle were
      preserved, then tested under the load of a specific weight in an Oxford knee rig.
      We designed a specialized rigid body with four active markers fixed to each bone
      to track the 3D passive motion of the cadaveric knees. Flexion and extension was
      controlled by the knee rig and captured by an Optotrak Certus high precision
      optical tracking system. The attachment sites of the patellar tendon were
      registered as virtual markers to calculate the 3D kinematics. RESULTS: The
      patellar tendon of the unaltered knee and both TKA knees showed similar
      deformation. We found the length of the patellar tendon changed significantly
      during a motion from full extension to 30 degrees , but there was no significant
      change in length while undergoing a motion from 30 degrees  to full flexion. Both
      the sagittal plane and coronal plane angles of the patellar tendon decreased
      after PS TKAs. There was no significant difference in patellar tendon kinematics
      between the two types of PS TKAs. CONCLUSION: We believe the changes observed in
      the sagittal plane and coronal plane angles of the patellar tendon after PS TKAs
      may influence the extensor mechanism and be an important cause of patella-femoral
      complications. These data may be used to assess patella-femoral complications
      after surgery so as to improve the design of high-flexion TKAs for Asians and
      achieve long-term stability.

PMID- 21097089
TI  - Developing a 6-DOF robot to investigate multi-axis ACL injuries under valgus
      loading coupled with tibia internal rotation.
AB  - Anterior cruciate ligament (ACL) injuries have become more common in recent years
      as more young people participate in risky sporting activities [1]. Most ACL
      injuries occur as a result of noncontact mechanisms. Previous in vitro studies of
      ACL strain have found significant increases in ACL strain primarily with anterior
      directed force on the tibia relative to the femur and with internal rotation and
      often with valgus torque [2,3]. However, there remains significant controversy
      over the mechanisms of ACL failure and the forces on the knee that lead to
      injury. Some studies have also shown that isolated valgus loading may not load
      the ACL strongly. The goal of this study was to investigate the mechanism
      underlying valgus-related ACL injuries. An improved understanding of ACL failure
      may lead to improved ACL injury prevention programs. A novel 6 degrees of freedom
      (DOF) knee driving robot was developed in this study with a unique multi-axis
      simultaneous torque/position control. It was found that pure valgus torque caused
      a torque that internally rotated the tibia and thus increased ACL strain
      markedly, which may be an important mechanism underlying the rather common
      seemingly valgus-related ACL injuries.

PMID- 21097090
TI  - Angle estimation of human femora in a three-dimensional virtual environment.
AB  - The estimation of human femur morphology and angulation provide useful
      information for assisted surgery, follow-up evaluation and prosthesis design,
      cerebral palsy management, congenital dislocation of the hip and fractures of the
      femur. Conventional methods that estimate femoral neck anteversion employ planar
      projections because accurate 3D estimations require complex reconstruction
      routines. In a recent work, we proposed a cylinder fitting method to estimate
      bifurcation angles in coronary arteries and we thought to test it in the
      estimation of femoral neck anteversion, valgus and shaft-neck angles. Femora from
      10 patients were scanned using multisliced computed tomography. Virtual cylinders
      were fitted to 3 regions of the bone painted by the user to automatically
      estimate the femoral angles. Comparisons were made with a conventional manual
      method. Inter- and intra-reading measurements were evaluated for each method. We
      found femoral angles from both methods strongly correlated. Average anteversion,
      neck-shaft and valgus angles were 17.5 degrees , 139.5 degrees , 99.1 degrees ,
      respectively. The repeatability and reproducibility of the automated method
      showed a 5-fold reduction in inter- and intra-reading variability. Accordingly,
      the coefficients of variation for the manual method were below 25% whereas for
      the automated method were below 6%. The valgus angle assessment was globally the
      most accurate with differences below 1 degrees . Maximum distances from true
      surface bone points and fitting cylinders attained 6 mm. The employment of
      virtual cylinders fitted to different regions of human femora consistently helped
      to assess true 3D angulations.

PMID- 21097091
TI  - Muscular activity during dynamic squats in patients with ACL reconstruction.
AB  - One of the most frequent injuries in subjects who practice sport is the rupture
      of the anterior cruciate ligament (ACL). Appropriate reconstruction and
      rehabilitation are key issues in full recovery of patients and their return to
      previous activities. This paper presents a new method to estimate muscle strength
      during a dynamic exercise from kinematic and electromyographic (EMG) data.
      Recovery of patients with ACL rupture and reconstruction was evaluated 4 and 6
      months after surgery by assessing the differences in knee extensor and flexor
      muscle activity between the unimpaired and injured limbs. The results show that
      squat EMGs from the extensor muscles of the knee from the injured and unimpaired
      limb could help assess rehabilitation outputs in patients who had undergone an
      ACL reconstructive surgery.

PMID- 21097092
TI  - Evaluation of fall and fall recovery in a simulated seismic environment: a pilot
      study.
AB  - Fall-related injuries, disabilities, and fatalities are known to seriously affect
      the healthcare and industry sectors. Nevertheless, an abled individual, as well
      as a trained senior citizen, is believed to be capable of withstanding and
      overcoming unusual environmental variations in terms of postural stability and
      balance. Understanding the biomechanics of fall and fall recovery through
      quantitative measurements could provide academic and methodical means to maintain
      human postural stability, of various ages, in such environments. This study
      assesses human performance and endurance in the most hazardous environment of a
      simulated violent seismic activity of a magnitude of 6.5 degrees on the Richter's
      scale. The objective is to evaluate fall and fall recovery in young abled adults
      using dynamic plantar pressure measurements. The obtained results support the
      hypothesis that falls in young adults could be prevented via exercise
      intervention programs. Further investigation is done by our research group to
      validate the same concept for senior citizens.

PMID- 21097093
TI  - A single camera stereographic imaging system for tracking upper limb motions.
AB  - A single camera stereographic imaging system was designed, built and tested for
      the intended application of tracking upper limb motion. The system consisted of a
      camera, quad-mirror system and image acquisition and processing software. This
      paper describes the design methods used and the testing of the system. Design
      methods included geometry optimisation and testing consisted of proof-of-concept
      trials. Preliminary results show that the concept is sound.

PMID- 21097094
TI  - Heart rate estimation on a beat-to-beat basis via ballistocardiography - a hybrid
      approach.
AB  - We present an algorithm for obtaining the heart rate from the signal of a single,
      contact-less sensor recording the mechanical activity of the heart. This vital
      parameter is required on a beat-to-beat basis for applications in sleep analysis
      and heart failure disease management. Our approach bundles information from
      various sources for first robust estimates. These estimates are further refined
      in a second step. An unambiguous comparison with the ECG RR-intervals taken as
      reference is possible for 98.5% of the heart beats. In these cases, a mean
      absolute error of 17 ms for the inter-beat interval lengths has been achieved,
      over a test corpus of 20 whole nights.

PMID- 21097095
TI  - Detection of vertebral plateaus in lateral lumbar spinal X-ray images with Gabor
      filters.
AB  - A few recent studies have proposed computed-aided methods for the detection and
      analysis of vertebral bodies in radiographic images. This paper presents a method
      based on Gabor filters. Forty-one lateral lumbar spinal X-ray images from
      different patients were included in the study. For each image, a radiologist
      manually delineated the vertebral plateaus of L1, L2, L3, and L4 using a software
      tool for image display and mark-up. Each original image was filtered with a bank
      of 180 Gabor filters. The angle of the Gabor filter with the highest response at
      each pixel was used to derive a measure of the strength of orientation or
      alignment. In order to limit the spatial extent of the image data and the derived
      features in further analysis, a semi-automated procedure was applied to the
      original image. A neural network utilizing the logistic sigmoid function was
      trained with pixel intensity from the original image, the result of manual
      delineation of the plateaus, the Gabor magnitude response, and the alignment
      image. The average overlap between the results of detection by image processing
      and manual delineation of the plateaus of L1-L4 in the 41 images tested was
      0.917. The results are expected to be useful in the analysis of vertebral
      deformities and fractures.

PMID- 21097096
TI  - Biospeckle image stack process based on artificial neural networks.
AB  - This paper proposes the identification of regions of interest in biospeckle
      patterns using unsupervised neural networks of the type Self-Organizing Maps.
      Segmented images are obtained from the acquisition and processing of laser
      speckle sequences. The dynamic speckle is a phenomenon that occurs when a beam of
      coherent light illuminates a sample in which there is some type of activity, not
      visible, which results in a variable pattern over time. In this particular case
      the method is applied to the evaluation of bacterial chemotaxis. Image stacks
      provided by a set of experiments are processed to extract features of the
      intensity dynamics. A Self-Organizing Map is trained and its cells are colored
      according to a criterion of similarity. During the recall stage the features of
      patterns belonging to a new biospeckle sample impact on the map, generating a new
      image using the color of the map cells impacted by the sample patterns. It is
      considered that this method has shown better performance to identify regions of
      interest than those that use a single descriptor. To test the method a chemotaxis
      assay experiment was performed, where regions were differentiated according to
      the bacterial motility within the sample.

PMID- 21097097
TI  - Skull segmentation in 3D neonatal MRI using hybrid Hopfield Neural Network.
AB  - A fully automated method for segmentation of neonatal skull in Magnetic Resonance
      (MR) images for source localization of electrical/magnetic encephalography
      (EEG/MEG) signals is proposed. Finding the source of these signals shows the
      origin of an abnormality. We propose a hybrid algorithm in which a Bayesian
      classifying framework is combined with a Hopfield Neural Network (HNN) for
      neonatal skull segmentation. Due to the non-homogeneity of skull intensities in
      MR images, local statistical parameters are used for adaptive training of
      Hopfield neural network based on Bayesian classifier error. The experimental
      results, which are obtained on high resolution T1-weighted MR images of nine
      neonates with gestational ages between 39 and 42 weeks, show 65% accuracy which
      consistently exhibits our scheme's superiority in comparison with previous
      neonatal skull segmentation methods.

PMID- 21097098
TI  - Spherical vision cameras in a semi-autonomous wheelchair system.
AB  - This paper is concerned with the methods developed for extending the capabilities
      of a spherical vision camera system to allow detection of surrounding objects and
      whether or not they pose a danger for movement in that direction during
      autonomous navigation of a power wheelchair. A Point Grey Research (PGR) Ladybug2
      spherical vision camera system was attached to the power wheelchair for
      surrounding vision. The objective is to use this Ladybug2 system to provide
      information about obstacles all around the wheelchair and aid the automated
      decision-making process involved during navigation. Through instantaneous neural
      network classification of individual camera images to determine whether obstacles
      are present, detection of obstacles have been successfully achieved with
      accuracies reaching 96%. This assistive technology has the purpose of automated
      obstacle detection, navigational path planning and decision-making, and collision
      avoidance during navigation.

PMID- 21097099
TI  - Multimodal method for cell membrane extraction in hepatic histological images.
AB  - A multimodal method, which uses different kinds of imaging methods, was applied
      to extract cell membranes in microscopic images of hematoxylin and eosin-stained
      hepatic histological sections. Cell membrane extraction in hepatic histological
      images is difficult because the color difference between the cell membrane and
      the cytoplasm is small in bright-field images. Three kinds of imaging methods,
      bright-field, dark-field, and phase-contrast imaging, were used because they are
      readily available for general pathologists. These imaging methods can be switched
      easily by revolving a combined condenser with the same phase-contrast objective
      lens. Therefore, little additional time and cost are needed for this approach.
      Experimental results show the effectiveness of this approach. The correct rate
      was improved by using additional color information obtained by dark-field and
      phase-contrast images compared to conventional bright-field images. The best
      correct rate was obtained when color information of all three images was used. A
      graphical user interface to calculate the N/C ratio was developed by combining
      cell membrane extraction with conventional cell nucleus extraction.

PMID- 21097100
TI  - Diffusion tensor driven contour closing for cell microinjection targeting.
AB  - This article introduces a novel approach to robust automatic detection of
      unstained living cells in bright-field (BF) microscope images with the goal of
      producing a target list for an automated microinjection system. The overall image
      analysis process is described and includes: preprocessing, ridge enhancement,
      image segmentation, shape analysis and injection point definition. The developed
      algorithm implements a new version of anisotropic contour completion (ACC) based
      on the partial differential equation (PDE) for heat diffusion which improves the
      cell segmentation process by elongating the edges only along their tangent
      direction. The developed ACC algorithm is equivalent to a dilation of the binary
      edge image with a continuous elliptic structural element that takes into account
      local orientation of the contours preventing extension towards normal direction.
      Experiments carried out on real images of 10 to 50 microm CHO-K1 adherent cells
      show a remarkable reliability in the algorithm along with up to 85% success for
      cell detection and injection point definition.

PMID- 21097101
TI  - Concentration of uric acid removed during dialysis. Estimated by multi wavelength
      and processed ultra violet absorbance spectra.
AB  - The aim of this study was to estimate the concentration of uric acid (UA)
      optically by using original and processed ultra violet (UV) absorbance spectra's
      of the spent dialysate. Also the effect of using several wavelengths for
      estimation was examined.

PMID- 21097102
TI  - An integrated imaging microscope for untethered cortical imaging in freely-moving
      animals.
AB  - Imaging in awake, behaving animals is an emerging field that offers the advantage
      of being able to study physiological processes and structures in a more natural
      state than what is possible in tissue slices or even in anesthetized animals. To
      date, most imaging in awake animals has used optical fiber bundles or electrical
      cables to transfer signals to traditional imaging-system components. However, the
      fibers or cables tether the animal and greatly limit the kind and duration of
      animal behavior that can be studied using imaging methods. We present an
      integrated imaging microscope (IIM) that incorporates all aspects of an imaging
      system - illumination, optics and photodetection - into a small footprint device,
      occupying under 4 cm(3) and weighing 5.4 g, that can be attached to the skull for
      imaging the brain in mobile rats. Power supply and image storage sufficient for
      approximately 7 hour operation at 15 frames/s was implemented on a backpack
      weighing 11.5 g. We implemented several optical techniques including reflectance,
      spectroscopy, speckle and fluorescence with the IIM, imaged vessels down to 15-20
      microm in diameter and obtained, to the best of our knowledge, the worlds first
      cortical images from an untethered, freely-moving rat.

PMID- 21097103
TI  - Frequency domain surface EMG sensor fusion for estimating finger forces.
AB  - Extracting or estimating skeletal hand/finger forces using surface electro
      myographic (sEMG) signals poses many challenges due to cross-talk, noise, and a
      temporal and spatially modulated signal characteristics. Normal sEMG measurements
      are based on single sensor data. In this paper, array sensors are used along with
      a proposed sensor fusion scheme that result in a simple Multi-Input-Single-Output
      (MISO) transfer function. Experimental data is used along with system
      identification to find this MISO system. A Genetic Algorithm (GA) approach is
      employed to optimize the characteristics of the MISO system. The proposed fusion
      based approach is tested experimentally and indicates improvement in finger/hand
      force estimation.

PMID- 21097105
TI  - Influence of temperature variations on the average grayscale of B-mode images of
      HIFU-induced lesions.
AB  - The aim of this work is to understand how the variations in grayscale values of B
      mode ultrasound (US) images can be used as an approach for non-invasive
      temperature estimation. In order to obtain real-time monitoring of HIFU
      treatment, an US imaging system and HIFU were synchronized. Images were acquired
      using an electronic convex imaging probe. An 8% BSA tissue-mimicking
      polyacrylamide gel was used for the experiments. First, the HIFU power was set to
      10 W. The application of HIFU resulted in the appearance of hyperechoic regions
      that were used to place a thermocouple tip at the focal spot by means of US
      imaging. Afterwards, the power was gradually increased up to 40 W for 4 min. The
      temperature sampling rate was set to 5 Hz. For each temperature sample the
      synchronization system captured one frame. The region of interest (ROI) was
      manually selected and a set of morphological operations were implemented in order
      to obtain the shape and size of the thermal lesion. From here, the average
      grayscale (AGS) and area of the thermal lesion were calculated to assess
      temperature quantification. The AGS parameter showed a maximum correlation
      coefficient of 0.6626 as a function of temperature whereas the thermal lesion
      appeared. In contrast, area values showed a greater correlation coefficient of
      0.9122. In conclusion, temperature shows a non-linear behavior with respect to
      the parameters estimated due to the nature of the thermal lesion formation by
      HIFU exposure.

PMID- 21097104
TI  - Fourier and wavelet spectral analysis of EMG signals in isometric and dynamic
      maximal effort exercise.
AB  - Frequency domain analyses of changes in electromyographic (EMG) signals over time
      are frequently used to assess muscle fatigue. Fourier based approaches are
      typically used in these analyses, yet Fourier analysis assumes signal
      stationarity, which is unlikely during dynamic contractions. Wavelet based
      methods of signal analysis do not assume stationarity and may be more appropriate
      for joint time-frequency domain analysis. The purpose of this study was to
      compare Short-Time Fourier Transform (STFT) and Continuous Wavelet Transform
      (CWT) in assessing muscle fatigue in isometric and dynamic exercise. The results
      of this study indicate that CWT and STFT analyses give similar fatigue estimates
      (slope of median frequency) in isometric and dynamic exercise (P>0.05). However,
      the results of the variance was lower for both types of exercise in CWT compared
      to STFT (P < 0.05) indicating more variability in the EMG signal analysis using
      STFT. Thus, the stationarity assumption may not be the sole factor responsible
      for affecting the Fourier based estimates.

PMID- 21097107
TI  - A new ultrasound imaging concept for laparoscopy in urology.
AB  - Intraoperative imaging performed by a video laparoscope is the gold standard
      during laparoscopic resections of tumors in urology. In contrast to ultrasound,
      laparoscopes cannot provide the surgeon with crucial information that could
      improve surgical outcome. Therefore, we developed a new concept for ultrasound
      imaging through the back of a supine patient during laparoscopic interventions.
      In this article we present a mock-up system to answer initial questions that were
      raised by the concept. The results of the performed experiments show that the
      concept is feasible.

PMID- 21097106
TI  - Miniaturized ultrasound imaging probes enabled by CMUT arrays with integrated
      frontend electronic circuits.
AB  - Capacitive micromachined ultrasonic transducer (CMUT) arrays are conveniently
      integrated with frontend integrated circuits either monolithically or in a hybrid
      multichip form. This integration helps with reducing the number of active data
      processing channels for 2D arrays. This approach also preserves the signal
      integrity for arrays with small elements. Therefore CMUT arrays integrated with
      electronic circuits are most suitable to implement miniaturized probes required
      for many intravascular, intracardiac, and endoscopic applications. This paper
      presents examples of miniaturized CMUT probes utilizing 1D, 2D, and ring arrays
      with integrated electronics.

PMID- 21097108
TI  - Computer assisted biopsy of breast tumors.
AB  - In this paper we report our preliminary results of the development of a computer
      assisted system for breast biopsy. The system is based on tracked ultrasound
      images of the breast. A three dimensional ultrasound volume is constructed from a
      set of tracked B-scan images acquired with a calibrated probe. The system has
      been designed to assist a radiologist during breast biopsy, and also as a
      training system for radiology residents. A semiautomatic classification algorithm
      was implemented to assist the user with the annotation of the tumor on an
      ultrasound volume. We report the development of the system prototype, tested on a
      physical phantom of a breast with a tumor, made of polivinil alcohol.

PMID- 21097109
TI  - Study of superficial basal cell carcinomas and Bowen disease by qualitative and
      quantitative ultrasound biomicroscopy approach.
AB  - In the present work the ultrasound biomicroscopy (UBM) technique is applied in
      the study of cutaneous cell carcinomas in vitro, including superficial basal cell
      carcinomas (BCC) and Bowen disease (BD) cases. The evaluation was made by
      qualitative observation of UBM images, and by quantitative computation of
      integrated backscatter coefficient (IBC), obtained with a system working at a
      central frequency of 45 MHz. The characteristic histological structures for each
      studied tumor type were well identified in the images. The IBC values observed in
      the two carcinoma types inside the affected region, were different between them,
      next to 10(-4) [Sr(-1).mm(-1)] for superficial BCC tissues, and to 10(-5) [Sr(
      1).mm(-1)1] for BD tissues; moreover, in the deeper dermis (slight affected
      region) the backscatter was next to 10(-3) [Sr(-1).mm(-1)] for both tissue
      groups, and agrees with the values obtained for healthy skin both, in this study
      and in previous works. The results here obtained encourage the continuation of
      the work, with a higher number of samples, attempting to obtain more significant
      results.

PMID- 21097110
TI  - Modeling and simulation of ultrasound fields generated by 2D phased array
      transducers for medical applications.
AB  - Modern ultrasound imaging instrumentation for clinical applications allows real
      time volumetric scanning of the patients' body. 4D imaging has been made possible
      thanks to the development of new echographic probes which consist in 2D phased
      arrays of piezoelectric transducers. In these new devices it is the system
      electronics which properly drives the matrix elements and focuses the beam in
      order to obtain a sequence of volumetric images. This paper introduces an
      ultrasound field simulator based on the Spatial Impulse Response method which is
      being properly developed to analyze the characteristics of the ultrasound field
      generated by a 2D phased array of transducers. Thanks to its high configurability
      by the user, it will represent a very useful tool for electronics designers in
      developing 4D ultrasound imaging systems components.

PMID- 21097112
TI  - Eigenbrains: The free vibrational modes of the brain as a new representation for
      EEG.
AB  - We present a new transform for EEG signals whose basis functions are well suited
      to represent the large-scale dynamics associated with event related potentials.
      The method involves instantiating an approximate model of the electrical
      properties of the brain as a conductor medium and then studying the free
      vibrational modes of the model. These form a set of basis functions, which we
      call eigenbrains, that can be used to meaningfully re-represent the brain's
      electrical activity. Eigenbrains are compared to principal component analysis and
      independent component analysis to highlight differences and similarities.

PMID- 21097111
TI  - Time-domain features of epileptic spikes as potential bio-markers of the
      epileptogenesis process.
AB  - Epilepsy is a neurological disorder characterized by recurrent seizures which
      affects about 1% people worldwide. During the past decades, some mechanisms
      involved in ictogenesis (generation of seizures) have been identified and, to
      some extent, partially understood. However, regarding epileptogenesis (process by
      which a neuronal system becomes epileptic), underlying mechanisms remain elusive.
      This difficulty is mostly related to the fact that epileptogenesis can only be
      addressed using experimental models. In this study, we have analyzed the shape of
      a specific electrophysiological pattern, referred to as "epileptic spike",
      encountered during the epileptogenesis process in an in vivo model of temporal
      lobe epilepsy (mouse, kainate). Results show that the features of these transient
      events (duration and amplitude) change as a function of time as the brain evolves
      towards the chronic epileptic state characterized by the appearance of
      spontaneous seizures. Using a detailed computational model of the hippocampus
      (CA1 sub-field), an interpretation of observed modifications is provided, in
      relationship with possible alterations that take place in underlying neuronal
      circuits.

PMID- 21097113
TI  - Brain surface electrode co-registration using MRI and X-ray.
AB  - Electrocorticographic recording is now being used in a wide variety of
      experimental settings. We present a simple method which can be used to estimate
      electrode position with respect to brain gyral anatomy using a pre-implantation
      MRI and post-implantation coronal and sagittal x-rays. It is semi-automated, with
      the user manually rotating and scaling an x-ray to fit brain outline, identifying
      threshold values for brain surface rendering, and clicking on electrodes on an x
      ray. Electrode positions can be rapidly identified and rendered in about 20
      minutes from start to finish. This approach is useful when the MRI quality is
      poor, there is no quality CT, but one would like to understand the relationship
      between experimental result and brain anatomy.

PMID- 21097114
TI  - A case study on the relation between electroencephalographic and
      electrocorticographic event-related potentials.
AB  - This study presents a preliminary analysis of the relationship between
      electroencephalographic (EEG) and electrocorticographic (ECoG) event-related
      potentials (ERPs) recorded from from a single patient using a brain-computer
      interface (BCI) speller. The patient had medically intractable epilepsy and
      underwent temporary placement of an intracranial ECoG grid electrode array to
      localize seizure foci. The patient performed one experimental session using the
      BCI spelling paradigm controlled by scalp-recorded EEG prior to the ECoG grid
      implantation, and one identical session controlled by ECoG after the grid
      implantation. The patient was able to achieve near perfect spelling accuracy
      using EEG and ECoG. An offline analysis of the average ERPs was performed to
      assess how accurately the average EEG ERPs could be predicted from the ECoG data.
      The preliminary results indicate that EEG ERPs can be accurately estimated from
      proximal asynchronous ECoG data using simple linear spatial models.

PMID- 21097115
TI  - Spatio-temporal clustering of firing rates for neural state estimation.
AB  - Characterizing the dynamics of neural data by a discrete state variable is
      desirable in experimental analysis and brain-machine interfaces. Previous
      successes have used dynamical modeling including Hidden Markov Models, but the
      methods do not always produce meaningful results without being carefully trained
      or initialized. We propose unsupervised clustering in the spatio-temporal space
      of neural data using time embedding and a corresponding distance measure. By
      defining performance measures, the method parameters are investigated for a set
      of neural and simulated data with promising results. Our investigations
      demonstrate a different view of how to extract information to maximize the
      utility of state estimation.

PMID- 21097116
TI  - Low-dimensional neural features predict muscle EMG signals.
AB  - Understanding the relationship between neural activity in motor cortex and muscle
      activity during movements is important both for basic science and for the design
      of neural prostheses. While there has been significant work in decoding muscle
      EMG from neural data, decoders often require many parameters which make the
      analysis susceptible to overfitting, which reduces generalizability and makes the
      results difficult to interpret. To address this issue, we recorded simultaneous
      neural activity from the motor cortices (M1/PMd) of rhesus monkeys performing an
      arm-reaching task while recording EMG from arm muscles. In this work, we focused
      on relating the mean neural activity (averaged across reach trials to one target)
      to the corresponding mean EMG. We reduced the dimensionality of the neural data
      and found that the curvature of the low-dimensional (low-D) neural activity could
      be used as a signature of muscle activity. Using this signature, and without
      directly fitting EMG data to the neural activity, we derived neural axes based on
      reaches to only one reach target (< 5% of the data) that could explain EMG for
      reaches across multiple targets (average R(2) = 0.65). Our results suggest that
      cortical population activity is tightly related to muscle EMG measurements,
      predicting a lag between cortical activity and movement generation of 47.5 ms.
      Furthermore, our ability to predict EMG features across different movements
      suggests that there are fundamental axes or directions in the low-D neural space
      along which the neural population activity moves to activate particular muscles.

PMID- 21097117
TI  - Diagnostic performance of the Forced Oscillation Technique in the detection of
      early respiratory changes in rheumatoid arthritis.
AB  - The objective of this study was to evaluate the clinical potential of the Forced
      Oscillation Technique (FOT) in the detection of the early alterations in
      respiratory mechanics of Rheumatoid Arthritis (RA) patients. A total of 36
      individuals were analyzed, 18 healthy and 18 with RA. The clinical usefulness of
      the parameters was evaluated investigating sensibility (Se), specificity (Sp) and
      the area under the receiver operating characteristic curve (AUC). In the RA
      group, all the 3 studied parameters obtained high accuracy for clinical use
      (AUC>0.9), while in spirometric parameters, no parameter obtained appropriate
      accuracy for clinical use (AUC < 0.7). In conclusion, the parameters obtained by
      FOT presented adequate Se and Sp, indicating that this technique can be helpful
      in the evaluation of the early respiratory mechanical alterations in patients
      with RA.

PMID- 21097118
TI  - Robust closed-loop control of propofol administration using WAVCNS index as the
      controlled variable.
AB  - This paper presents a robust closed-loop strategy for control of depth of
      hypnosis. The proposed method regulates the electroencephalogram (EEG)-derived
      WAVCNS index as a hypnosis measure by manipulating intravenous propofol
      administration. In contrast to many existing closed-loop methods, the control
      design presented in this paper produces stability and robustness against
      uncertainty by explicitly accounting for the pharmacokinetic (PK) and
      pharmacodynamic (PD) variability between different individuals, as well as
      unpredictable surgical stimuli that the closed-loop control is required to
      tolerate. This closed-loop control was evaluated using simulated surgical
      procedures in 44 patient models whose PK and PD were identified from real
      clinical data. The controller can deliver consistent and acceptable closed-loop
      induction and maintenance phase responses for patients with wide-ranging PK and
      PD differences.

PMID- 21097119
TI  - Clinical engineering development in the Uruguayan public health system.
AB  - Establishment of the clinical engineering department with a network of 5
      operational centers to strengthen public medical equipment management and
      maintenance, in the context of the Health System reform with the purpose of
      ensuring universal access to the health services in the Republic of Uruguay.

PMID- 21097120
TI  - Morphological descriptors as rupture indicators in middle cerebral artery
      aneurysms.
AB  - The rupture of intracranial aneurysms is associated to significant morbidity and
      mortality rates. Although the mechanisms triggering this event are still unclear,
      morphology is among the factors considered by interventional neuroradiologists to
      decide treatment. The aim of this work is to explore the potential of
      morphological descriptors as rupture risk predictors in middle cerebral artery
      aneurysms (MCA) and to provide the subset showing the best predictive
      capabilities. The set of evaluated descriptors include basic shape descriptors
      related to the aneurysm size, and most sophisticated ones such as the Zernike
      Moment Invariants. The population analyzed included 71 patients harboring 86 MCA
      aneurysms (64 unruptured vs. 22 ruptured). An existing image-based processing
      pipeline was used to extract such descriptors from Three-Dimensional Rotational
      Angiography (3DRA) images routinely acquired during standard clinical practice.
      Univariate and multivariate statistical analyses have shown that among the
      evaluated descriptors, Zernike moment invariants computed on the aneurysm and a
      small portion of the surrounding vessels, together with the non-sphericity index,
      provide the best predictive capabilities of aneurysm rupture.

PMID- 21097121
TI  - Development of modified intraoperative examination monitor for awake surgery
      (IEMAS) system for awake craniotomy during brain tumor resection.
AB  - Gliomas represent the most frequent type of primary intracranial tumors, which
      originate from the brain tissue itself, have infiltrative growth, unclear
      borders, and usually affect functionally-important cerebral structures. From
      March 2000 till March 2010, 839 neurosurgical procedures directed on resection of
      such neoplasms were performed in the intelligent operating theater of Tokyo
      Women's Medical University with the use of intraoperative MRI, real-time updated
      neuronavigation system, and Hi-vision operative microscope. To facilitate maximal
      possible tumor resection with minimal risk of neurological morbidity a special
      device, called Intraoperative Examination Monitor for Awake Surgery (IEMAS) was
      developed by us. It provides an opportunity to visualize a wide spectrum of
      inraoperative information related to condition of the patient, nuances of the
      surgical procedure, and details of the cortical mapping. The wide set of both
      anatomical and functional parameters, such as view of the patient's mimic and
      face movements during answering on the specific questions, type of examination
      test, position of the surgical instruments, parameters of the bispectral index
      monitor, and general view of the surgical field through the operating microscope
      and/or endoscope, is presented compactly in one screen with several displays,
      which allows fast integrated real-time analysis of the multiple data, nearly
      without interruption of the surgical manipulations. All members of the surgical
      team can share this information using several in-room liquid crystal displays.
      However, the initially designed IEMAS system was occasionally affected by
      interruption or detachment of the connecting cables, which could interfere with
      effective advancement of the surgical procedure. To avoid this problem a modified
      device was created. Its specific feature is wireless information transmitting
      function attained by incorporation of transmitters with a frequency range of 2.4
      GHz. The clinical testing of t- - his system was initiated on February 1, 2010,
      but quickly revealed crossed line effect between transmitters and receivers. To
      overcome this obstacle and to isolate transmitters, one channel was changed from
      wireless connection into wired, which resulted in significant improvement of the
      clearness of both transmitted images and sounds, and provides an opportunity for
      effective clinical use of the device. In perspective we wish to make IEMAS system
      fully wireless, using several types of frequency range transmitters.

PMID- 21097122
TI  - A framework of medical equipment management system for in-house clinical
      engineering department.
AB  - Medical equipment management is an important issue for safety and cost in modern
      hospital operation. In addition, the use of an efficient information system
      effectively promotes the managing performance. In this study, we designed a
      framework of medical equipment management system used for in-house clinical
      engineering department. The system was web-based, and it integrated clinical
      engineering and hospital information system components. Through related
      information application, it efficiently improved the operation management of
      medical devices immediately and continuously. This system has run in the National
      Taiwan University Hospital. The results showed only few examples in the error
      analysis of medical equipment by the maintenance sub-system. The information can
      be used to improve work quality, to reduce the maintenance cost, and to promote
      the safety of medical device used in patients and clinical staffs.

PMID- 21097123
TI  - Multimodal EEG, MRI and PET data fusion for Alzheimer's disease diagnosis.
AB  - Alarmingly increasing prevalence of Alzheimer's disease (AD) due to the aging
      population in developing countries, combined with lack of standardized and
      conclusive diagnostic procedures, make early diagnosis of Alzheimer's disease a
      major public health concern. While no current medical treatment exists to stop or
      reverse this disease, recent dementia specific pharmacological advances can slow
      its progression, making early diagnosis all the more important. Several
      noninvasive biomarkers have been proposed, including P300 based EEG analysis, MRI
      volumetric analysis, PET based metabolic activity analysis, as alternatives to
      neuropsychological evaluation, the current gold standard of diagnosis. Each of
      these approaches, have shown some promising outcomes, however, a comprehensive
      data fusion analysis has not yet been conducted to investigate whether these
      different modalities carry complementary information, and if so, whether they can
      be combined to provide a more accurate analysis. In this effort, we provide a
      first look at such an analysis in combining EEG, MRI and PET data using an
      ensemble of classifiers based decision fusion approach, to determine whether a
      strategic combination of these different modalities can improve the diagnostic
      accuracy over any of the individual data sources when used with an automated
      classifier. Results show an improvement of up to 10%-20% using this approach
      compared to the classification performance obtained when using each individual
      data source.

PMID- 21097124
TI  - Dynamic neural network detection of tremor and dyskinesia from wearable sensor
      data.
AB  - We present a dynamic neural network (DNN) solution for detecting time-varying
      occurrences of tremor and dyskinesia at 1 s resolution from time series data
      acquired from surface electromyographic (sEMG) sensors and tri-axial
      accelerometers worn by patients with Parkinson's disease (PD). The networks were
      trained and tested on separate datasets, each containing approximately equal
      proportions of tremor, dyskinesia, and disorder-free data from 8 PD and 4 control
      subjects performing unscripted and unconstrained activities in an apartment-like
      environment. During DNN testing, tremor was detected with a sensitivity of 93%
      and a specificity of 95%, while dyskinesia was detected with a sensitivity of 91%
      and a specificity of 93%. Similar sensitivity and specificity levels were
      obtained when DNN testing was carried out on subjects who were not included in
      DNN training.

PMID- 21097125
TI  - Multichannel surface EMG based estimation of bilateral hand kinematics during
      movements at multiple degrees of freedom.
AB  - The paper proposes a method to estimate wrist kinematics from surface EMG signals
      for proportional and simultaneous control of multiple degrees of freedom (DOFs).
      The approach is based on the concurrent detection of surface EMG signals from
      forearm muscles and hand kinematics of both limbs during mirrored bilateral
      movements in free space which involve the simultaneous activation of wrist
      flexion/extension, radial/ulnar deviation and forearm pronation/supination. The
      estimation was based on one multilayer perceptron (MLP) neural network for each
      DOF. The three MLPs were trained to estimate angular displacements corresponding
      to the three DOFs. The average coefficient of determination between the true and
      the predicted angular displacement was 82.7 +/- 2.9% (80.9 +/- 3.4%) for
      flexion/extension, 75.0 +/- 3.8% (72.6 +/- 9.4%) for radial/ulnar deviation, 76.6
      +/- 11.8% (75.1 +/- 11.7%) for pronation/supination for the ipsi-lateral (contra
      lateral) hand. The scheme represents a step forward towards the simultaneous
      control of DOFs and thus a more natural prosthetic control.

PMID- 21097126
TI  - Multi-parameter analysis of ECG and respiratory flow signals to identify success
      of patients on weaning trials.
AB  - Statistical analysis, power spectral density, and Lempel Ziv complexity, are used
      in a multi-parameter approach to analyze four temporal series obtained from the
      Electrocardiographic and Respiratory Flow signals of 126 patients on weaning
      trials. In which, 88 patients belong to successful group (SG), and 38 patients
      belong to failure group (FG), i.e. failed to maintain spontaneous breathing
      during trial. It was found that mean values of cardiac inter-beat and breath
      durations give higher values for SG than for FG; Kurtosis coefficient of the
      spectrum of the rapid shallow breathing index is higher for FG; also Lempel Ziv
      complexity mean values associated with the respiratory flow signal are bigger for
      FG. Patients were then classified with a pattern recognition neural network,
      obtaining 80% of correct classifications (81.6% for FG and 79.5% for SG).

PMID- 21097127
TI  - Diagnosis of brain tumours from magnetic resonance spectroscopy using wavelets
      and Neural Networks.
AB  - The diagnosis of human brain tumours from noninvasive signal measurements is a
      sensitive task that requires specialized expertise. In this task, radiology
      experts are likely to benefit from the support of computer-based systems built
      around robust classification processes. In this brief paper, a method that
      combines data pre-processing using wavelets with classification using Artificial
      Neural Networks is shown to yield high diagnostic classification accuracy for a
      broad range of brain tumour pathologies.

PMID- 21097128
TI  - Development of a pediatric cardiac computer aided auscultation decision support
      system.
AB  - Developing countries have a large population of children living with undiagnosed
      heart murmurs. As a result of an accompanying skills shortage, most of these
      children will not get the necessary treatment. The objective of this paper was to
      develop a decision support system. This could enable health care providers in
      developing countries with tools to screen large amounts of children without the
      need for expensive equipment or specialist skills. For this purpose an algorithm
      was designed and tested to detect heart murmurs in digitally recorded signals. A
      specificity of 94% and a sensitivity of 91% were achieved using novel signal
      processing techniques and an ensemble of neural networks as classifier.

PMID- 21097129
TI  - An integrative model of the surface EMG in pathological tremor.
AB  - A novel integrative model for simulating the surface EMG signal during
      pathological tremor is presented. The model combines neuromuscular elements,
      biomechanical descriptions, and surface EMG generation. First single motor unit
      spike trains are generated based on the sum of the simulated descending drive,
      afferent input and an oscillatory noise causing tremor. Based on this activity
      pattern, the muscle force is estimated, from which the limb movement is derived.
      The surface EMG is simulated as the sum of the surface action potentials
      generated by the active motor units. The model was able to simulate several
      features of tremor that have been previously observed experimentally, including
      the spectral characteristics of the surface EMG during tremor and the pattern of
      activity of single motor units.

PMID- 21097130
TI  - Parkinson's disease identification through optimum-path forest.
AB  - Artificial intelligence techniques have been extensively used for the
      identification of several disorders related with the voice signal analysis, such
      as Parkinson's disease (PD). However, some of these techniques flaw by assuming
      some separability in the original feature space or even so in the one induced by
      a kernel mapping. In this paper we propose the PD automatic recognition by means
      of Optimum-Path Forest (OPF), which is a new recently developed pattern
      recognition technique that does not assume any shape/separability of the
      classes/feature space. The experiments showed that OPF outperformed Support
      Vector Machines, Artificial Neural Networks and other commonly used supervised
      classification techniques for PD identification.

PMID- 21097131
TI  - Influence of evoked response latency and amplitude on stimulus artifact removal.
AB  - The removal of stimulus artifacts is a challenge not only to evoked potentials
      but also to other electrically-elicited signals such as M wave and direct
      cortical responses. Several techniques try to remove stimulus artifacts. However,
      the influence of the amplitude ratio between signal and artifact has not been
      reported yet. Neither has been the effect of the delay between stimulus and
      signal. So, this work aimed to study the relationship between the evoked
      response's parameters (amplitude; latency) and the associated errors, for several
      amplitude ratios and delays between stimulus artifact and evoked response
      simulation models. In order to do so, the evoked responses were represented by a
      mathematical function with varying amplitudes and latencies. The stimulus
      artifacts were represented by the concatenation of a rectangular bipolar pulse
      and three exponential functions. Reasonable results were obtained for these
      models, whenever the amplitude ratio between evoked response and artifact was
      between 5% and 40%, and the evoked response's latency was within the range of 3ms
      to 8ms. These results showed that the technique has the potential to contribute
      to stimulus artifact removal on somatosensory evoked potentials recorded at the
      elbow, for both wrist and hand stimulation of the median nerve.

PMID- 21097132
TI  - Automatic detection of layer activation order in information processing pathways
      of rat barrel cortex under mechanical whisker stimulation.
AB  - Whisking is the natural way by which rodents explore the environment. During
      whisking, microcircuits in the corresponding barrel columns get activated to
      segregate and integrate the tactile information through the information
      processing pathway. The local field potentials (LFPs) recorded from the barrel
      columns provide important information about this pathway. Different layers of the
      cortex get activated during this information processing, thus having precise
      information about the order of layer activation is desired. This work proposes an
      automated, computationally efficient and easy to implement method to determine
      the cortical layer activation for the signals recorded from barrel cortex of
      anesthetized rats upon mechanical whisker stimulation.

PMID- 21097133
TI  - Exploring high-frequency oscillation as a marker of brain ischemia using S
      transform.
AB  - Brain injury, such as hypoxic-ischemia produced in brain after cardiac arrest, is
      known to alter somatosensory evoked potential (SSEP) signals, thus serving a
      diagnostic role. This study explores the high-frequency oscillation (HFO) in SSEP
      recorded in a rat model of asphyxial cardiac arrest. To best characterize this
      complex oscillatory activity, several time-frequency representation strategies
      are implemented and compared. The S-transform (ST) is found to precisely localize
      the HFO in temporal-spectral space. More, the 'phase ST'-the inter-trial
      coherence (ITC) sensitively detects the phase-locked activities in HFO. Using ST
      and ITC, we explored the evolution of HFO during early recovery from brain
      injury. A discrepancy between the amplitude of HFO, which increases over time,
      and its phase, which stays time-invariant, is revealed here. The recovery
      dynamics of HFO mirrors that of N10 in terms of their amplitudes, which suggests
      HFO as a prelude of large-scale cortical responses. In addition, statistics shows
      the amplitudes of HFOs have different levels (p < 0.05) and recovery dynamics
      (p=0.03) between the good- and bad-outcome groups. We consider the HFO to be
      reflective of the health of thalamocotical circuitry in brain ischemia.

PMID- 21097134
TI  - Using pre-treatment EEG data to predict response to SSRI treatment for MDD.
AB  - The problem of identifying in advance the most effective treatment agent for
      various psychiatric conditions remains an elusive goal. To address this
      challenge, we propose a machine learning (ML) methodology to predict the response
      to a selective serotonin reuptake inhibitor (SSRI) medication in subjects
      suffering from major depressive disorder (MDD), using pre-treatment
      electroencephalograph (EEG) measurements. The proposed feature selection
      technique is a modification of the method of Peng et al [10] that is based on a
      Kullback-Leibler (KL) distance measure. The classifier was realized as a
      kernelized partial least squares regression procedure, whose output is the
      predicted response. A low-dimensional kernelized principal component
      representation of the feature space was used for the purposes of visualization
      and clustering analysis. The overall method was evaluated using an 11-fold nested
      cross-validation procedure for which over 85% average prediction performance is
      obtained. The results indicate that ML methods hold considerable promise in
      predicting the efficacy of SSRI antidepressant therapy for major depression.

PMID- 21097135
TI  - Negotiating your first BME job: Do's and don'ts in academia, private sector and
      government.
AB  - This session is intended to prepare current bioengineering students and post
      doctoral fellows, getting them in the right shape to apply, negotiate and succeed
      in getting their first job in industry or academia. Tips on putting together the
      appropriate CV, preparing your portfolio and getting ready for the interview will
      be covered by the invited speakers. The panel will consist of representatives
      from academia and the private sector, as well as government and regulators. This
      session aims to give you some all-round pointers on the dos and donts towards
      choosing, applying, attending an interview and negotiating your future position
      as a young biomedical engineer.

PMID- 21097136
TI  - Ultrasonographic characterization and identification of symptomatic carotid
      plaques.
AB  - Carotid plaques are the main cause of neurological symptoms due to distal
      embolization or flow reduction. An objective classification of such lesions into
      symptomatic or asymptomatic is crucial for optimal treatment planning.

PMID- 21097137
TI  - Edge-based partial volume averaging estimation for FLAIR MRI with white matter
      lesions.
AB  - Through the combination of intensity and fuzzy edge strength measures, a new
      partial volume averaging (PVA) quantification technique for FLAIR MRI with white
      matter lesions (WML) is developed. It is focused on an edge-based approach, which
      "probes" for PVA voxels via a global estimate for the change in the proportion of
      tissues alpha'. This estimate is refined according to a probabilistic threshold,
      and the result is decoded to find the proportion of tissues fraction alpha - the
      percentage of one tissue found in a mixture voxel. The results from several
      images are shown illustrating how the technique may be used to segment PVA and
      pure tissue classes. The result is a non-model based approach to the detection
      and quantification of PVA.

PMID- 21097138
TI  - Exploratory matrix factorization for PET image analysis.
AB  - Features are extracted from PET images employing exploratory matrix factorization
      techniques such as nonnegative matrix factorization (NMF). Appropriate features
      are fed into classifiers such as a support vector machine or a random forest tree
      classifier. An automatic feature extraction and classification is achieved with
      high classification rate which is robust and reliable and can help in an early
      diagnosis of Alzheimer's disease.

PMID- 21097139
TI  - Automatic analysis of macroarrays images.
AB  - The analysis of dot blot (macroarray) images is currently based on the human
      identification of positive/negative dots, which is a subjective and time
      consuming process. This paper presents a system for the automatic analysis of dot
      blot images, using a pre-defined grid of markers, including a number of ON and
      OFF controls. The geometric deformations of the input image are corrected, and
      the individual markers detected, both tasks fully automatically. Based on a
      previous training stage, the probability for each marker to be ON is established.
      This information is provided together with quality parameters for training, noise
      and classification, allowing for a fully automatic evaluation of a dot blot
      image.

PMID- 21097140
TI  - Grouping a few sets of normally distributed voxels of SPECT volumes in
      discrimination between Alzheimer dementia and controls.
AB  - It is widely accepted and can be easily verified that any specific voxel in a
      class of brain single photon emission computed tomography (SPECT) volumes is of a
      univariate normal distribution. In this research, we conjecture that all the
      voxels in a class of SPECT volumes are also approximately of a multivariate
      normal (MVN) distribution from which in terms of the Bayes errors of statistics,
      an optimal classifier can be designed using quadratic discriminant functions
      (QDFs). However, the number of training volumes needed for deriving the
      covariance matrix of an MVN distribution increases quadratically with respect to
      the number of voxels such that practically the MVN distributions cannot be
      modeled. To overcome this, we selected a reduced number of voxels and put them
      into groups based on the P values of two-sided t tests or a greedy algorithm of
      discrimination between two classes of volumes. We also tried the same approach on
      the 3D Haar wavelet coefficients which were obtained from the discrete wavelet
      transform of the voxels. Experiments showed that the accuracies of QDFs, linear
      discriminant functions (LDFs), and support vector machines (SVMs) were not
      significantly different in discrimination between Alzheimer's and normal controls
      verifying that the proposed MVNs effectively model the discrimination
      information. Moreover, the proposed QDF classifier obtained satisfactory
      performance.

PMID- 21097141
TI  - Modeling spatial relation in skin lesion images by the graph walk kernel.
AB  - Early skin cancer detection with the help of dermoscopic images is becoming more
      and more important. Previous methods generally ignored the spatial relation of
      the pixels or regions inside the lesion. We propose to employ a graph
      representation of the skin lesion to model the spatial relation. We then use the
      graph walk kernel, a similarity measure between two graphs, to build a classifier
      based on support vector machines for melanoma detection. In experiments, we
      compare the sensitivities and specificities of models with and without spatial
      information. Experimental results show that the model with spatial information
      performs the best in both sensitivity and specificity. Statistical test indicates
      that the improvement is significant.

PMID- 21097142
TI  - Autonomic and metabolic effects of OSA in childhood obesity.
AB  - This study investigates the effects of exposure to intermittent hypoxia on
      cardiovascular autonomic control and metabolic function in obese children with
      obstructive sleep apnea (OSA). Each subject underwent: (1) a polysomnography; (2)
      morning fasting blood samples and a subsequent FSIVGTT; (3) noninvasive
      measurement of respiration, arterial blood pressure, and heart rate during supine
      and standing postures. Assessment of adiposity was performed using a DEXA scan.
      From these measurements, we deduced the pertinent sleep parameters, Bergman
      minimal model parameters and the parameters characterizing a minimal model of
      cardiovascular variability. Results suggest that intermittent hypoxia in OSA
      contributes independently to insulin resistance and autonomic dysfunction in
      overweight children.

PMID- 21097143
TI  - Regular and non regular snore features as markers of SAHS.
AB  - Sleep Apnea-Hypopnea Syndrome (SAHS) diagnosis is still done with an overnight
      multi-channel polysomnography. Several efforts are being made to study profoundly
      the snore mechanism and discover how it can provide an opportunity to diagnose
      the disease. This work introduces the concept of regular snores, defined as the
      ones produced in consecutive respiratory cycles, since they are produced in a
      regular way, without interruptions. We applied 2 thresholds (TH(adaptive) and
      TH(median)) to the time interval between successive snores of 34 subjects in
      order to select regular snores from the whole all-night snore sequence.
      Afterwards, we studied the effectiveness that parameters, such as time interval
      between successive snores and the mean intensity of snores, have on
      distinguishing between different levels of SAHS severity (AHI (Apnea-Hypopnea
      Index) < 5h(-1), AHI <10 h(-1), AHI < 15 h(-1), AHI < 30 h(-1)). Results showed
      that TH(adaptive) outperformed TH(median) on selecting regular snores. Moreover,
      the outcome achieved with non-regular snores intensity features suggests that
      these carry key information on SAHS severity.

PMID- 21097144
TI  - Automatic non-invasive differentiation of obstructive and central hypopneas with
      nasal airflow compared to esophageal pressure.
AB  - The differentiation of obstructive and central respiratory events is a major
      challenge in the diagnosis of sleep disordered breathing. Esophageal pressure
      (Pes) measurement is the gold-standard method to identify these events but its
      invasiveness deters its usage in clinical routine. Flattening patterns appear in
      the airflow signal during episodes of inspiratory flow limitation (IFL) and have
      been shown with invasive techniques to be useful to differentiate between central
      and obstructive hypopneas. In this study we present a new method for the
      automatic non-invasive differentiation of obstructive and central hypopneas
      solely with nasal airflow. An overall of 36 patients underwent full night
      polysomnography with systematic Pes recording and a total of 1069 hypopneas were
      manually scored by human experts to create a gold-standard annotation set.
      Features were automatically extracted from the nasal airflow signal to train and
      test our automatic classifier (Discriminant Analysis). Flattening patterns were
      non-invasively assessed in the airflow signal using spectral and time analysis.
      The automatic non-invasive classifier obtained a sensitivity of 0.71 and an
      accuracy of 0.69, similar to the results obtained with a manual non-invasive
      classification algorithm. Hence, flattening airflow patterns seem promising for
      the non-invasive differentiation of obstructive and central hypopneas.

PMID- 21097145
TI  - Nocturnal sound analysis for the diagnosis of obstructive sleep apnea.
AB  - A novel method for screening obstructive sleep apnea syndrome (OSAs) based on
      nocturnal acoustic signal is proposed. Full-night audio signals from sixty
      subjects were segmented into snore, noise and silence events using semi-automatic
      algorithm based on Gaussian mixture models which achieves more than 90% (92%)
      sensitivity (specificity) and produces an average of 2,000 snores per subject. A
      classification into 3 groups is proposed for the diagnosis: comparison group -
      non-OSA subjects (apnea hypopnea index, AHI < 10), mild to moderate OSA (10 < AHI
      < 30) and severe OSA (AHI>30). A Bayes classifier was implemented, fed with five
      acoustic features, all correlated with the severity of the syndrome: (1) Inter
      Event Silence, which quantifies segments suspicious as apnea; (2) Mel
      Cepstability, measures the entire night stability of the spectrum, expressed
      using mel-frequency cepstrum; (3) Energy Running Variance, a criterion for the
      variation of the nocturnal acoustic pattern; (4) Apneic Phase Ratio, exploiting
      the finding that snores around apnea events expressing larger acoustic variation;
      and (5) Pitch Density. Correct classification of 92% for resubstitution method
      and 80% for 5-fold cross validation method was achieved. Moreover, in a case of
      two groups with a threshold of AHI=10, a sensitivity (specificity) of 96.5%
      (90.6%) and 87.5% (82.1%) for resubstitution and cross-validation respectively
      were obtained.

PMID- 21097146
TI  - Development of a continuous multisite accelerometry system for studying movements
      during sleep.
AB  - Actigraphy has proven to be a useful tool in the assessment of circadian rhythms,
      and more recently in the automatic staging of sleep and wake states. Whilst
      accuracy of commercial systems appears good over 24 hour periods, the sensitivity
      of detecting wake during time in bed is poor. One possible explanation for these
      poor results is the technical limitations of currently available commercial
      actigraphs. In particular, raw data is generally not available to the user.
      Instead, activity counts for each epoch (typically between 10-60 secs) are
      calculated using various algorithms, from which sleep state is identified.
      Consequently morphologically different movements observed during sleep and wake
      states may not be detected as such. In this paper, the development of a
      continuous multisite, accelerometry system (CMAS) is described. Initial results,
      comparing data collected using a commercial actigraph (Actiwatch- Mini
      Motionlogger), and the continuous multisite accelerometry system are presented.
      The CMAS is able to differentiate brief movement "twitches" from postural
      changes.

PMID- 21097147
TI  - Pediatric obstructive sleep apnea assessment using pulse oximetry and dual RIP
      bands.
AB  - The diagnosis of Obstructive Sleep Apnea (OSA) in children presents a challenging
      diagnostic problem given the high prevalence (2-3%), the resource intensity of
      the overnight polysomnography investigation, and the realisation that OSA poses a
      serious threat to the healthy growth and development of children. Previous
      attempts to develop OSA diagnostic systems using home pulse oximetry studies have
      failed to meet the accuracy requirements - particularly the low false normal rate
      (FNR) - required for a pre-PSG screening test. Thus the aim of this study is to
      investigate the feasibility of an OSA severity diagnostic system based on both
      oximetry and dual respiratory inductance plethysmography (RIP) bands. A total of
      90 PSG studies (30 each of normal, mild/moderate and severe OSA) were
      retrospectively analyzed. Quantifications of oxygen desaturations (S),
      respiratory events (E) and heart rate arousals (A) were calculated and extracted
      and an empirical rule-based SEA classifier model for normal, mild/moderate and
      severe OSA defined and developed. In addition, an automated classifier using a
      decision tree algorithm was trained and tested using a 10-fold cross-validation.
      The empirical classification system showed a correct classification rate (CCR) of
      0.83 (Cohen's Kappa kappa=0.81, FNR=0.08), and the decision tree classifier
      achieved a CCR of 0.79 (kappa=0.73, FNR=0.08) when compared to gold standard PSG
      assessment. The relatively high CCR, and low FNR indicate that a OSA severity
      system based on dual RIP and oximetry is feasible for application as a pre-PSG
      screening tool.

PMID- 21097148
TI  - An accurate and interpretable model for BCCT.core.
AB  - Breast Cancer Conservative Treatment (BCCT) is considered nowadays to be the most
      widespread form of locor-regional breast cancer treatment. However, aesthetic
      results are heterogeneous and difficult to evaluate in a standardized way. The
      limited reproducibility of subjective aesthetic evaluation in BCCT motivated the
      research towards objective methods. A recent computer system (BCCT.core) was
      developed to objectively and automatically evaluate the aesthetic result of BCCT.
      The system is centered on a support vector machine (SVM) classifier with a radial
      basis function (RBF) used to predict the overall cosmetic result from features
      computed on a digital photograph of the patient. However, this classifier is not
      ideal for the interpretation of the factors being used in the prediction.
      Therefore, an often suggested improvement is the interpretability of the model
      being used to assess the overall aesthetic result. In the current work we
      investigate the accuracy of different interpretable methods against the model
      currently deployed in the BCCT.core software. We compare the performance of
      decision trees and linear classifiers with the RBF SVM currently in BCCT.core. In
      the experimental study, these interpretable models shown a similar accuracy to
      the currently used RBF SVM, suggesting that the later can be replaced without
      sacrificing the performance of the BCCT.core.

PMID- 21097149
TI  - SeyeS - support system for preventing the development of ocular disabilities in
      leprosy.
AB  - Leprosy is an infectious disease caused by Mycobacterium Leprae, and generally
      compromises neural fibers, leading to the development of disabilities. These
      limit daily activities or social life. In leprosy, the study of disability
      considered functional (physical) and activity limitations; and social
      participation. These are measured respectively by EHF and SALSA scales; by and
      PARTICIPATION SCALE: The objective of this work was to propose a support system,
      SeyeS, to eyes disabilities development and progression identification, applying
      Bayesians network - BN's. It is expected that the proposed system be applied in
      monitoring the patient during treatment and after therapeutic cure of leprosy.
      SeyeS presented specificity 1 and sensitivity 0.6 in the identification of ocular
      disabilities development. With Seyes was discovered that the presence of
      trichiasis and lagophthalmos, tend to increase the probability of developing more
      disabilities. Otherwise, characteristics as cataracts tend to decrease
      development of other disabilities, considering that medical interventions could
      reduce it. The more import of this system is to indicate what should be
      monitored, and which elements needs interventions to not increasing patient's
      ocular disabilities.

PMID- 21097150
TI  - A guideline-based decision support system for generating referral recommendations
      from routinely recorded home telehealth measurement data.
AB  - The objectives of this paper are to present a guideline-based decision support
      system (GBDSS) design for supporting patient telehealth management of chronic
      disease and to test its performance in correctly making referral recommendations
      using routinely recorded measurement data from home telehealth recordings. The
      GBDSS has been developed to manage lung disease patients in a home telehealth
      environment. The system operates by checking the availability of home telehealth
      measurement data on a daily basis, interprets these data using a rule-based
      decision tree classification, and ultimately generates referral recommendations
      based on these measured data. The system has demonstrated discriminative power
      when applied in the analysis of retrospective telehealth data, as a surrogate for
      realtime referral generation. To this end a telehealth dataset comprising 16
      chronic obstructive pulmonary disease (COPD) patients monitored over a 12 month
      period was used. It was shown that GBDSS referral recommendations could help
      reduce the number of cases that required a carer's urgent attention by 72.1%,
      with 81.9% accuracy, 80.8% specificity and 90.4% sensitivity.

PMID- 21097151
TI  - Hybrid cost-sensitive fuzzy classification for breast cancer diagnosis.
AB  - Breast cancer is the most commonly diagnosed form of cancer in women accounting
      for about 30% of all cases. From a computational point of view, breast cancer
      diagnosis can be viewed as a pattern classification problem. In this paper, we
      present a cost-sensitive approach to classifying breast cancer data. In
      particular, we employ a fuzzy rule base that allows incorporation of a
      misclassification cost term in order to provide the ability to focus on certain
      classes and hence to boost the identification of malignant cases. Moreover, we
      show how genetic algorithms can be employed to optimise a compact yet effective
      rule base, investigating both Michigan and Pittsburgh style approaches of hybrid
      GA-fuzzy classifiers in the context of breast cancer diagnosis.

PMID- 21097152
TI  - Compression-based aggregation model for medical web services.
AB  - Many organizations such as hospitals have adopted Cloud Web services in applying
      their network services to avoid investing heavily computing infrastructure. SOAP
      (Simple Object Access Protocol) is the basic communication protocol of Cloud Web
      services that is XML based protocol. Generally,Web services often suffer
      congestions and bottlenecks as a result of the high network traffic that is
      caused by the large XML overhead size. At the same time, the massive load on
      Cloud Web services in terms of the large demand of client requests has resulted
      in the same problem. In this paper, two XML-aware aggregation techniques that are
      based on exploiting the compression concepts are proposed in order to aggregate
      the medical Web messages and achieve higher message size reduction.

PMID- 21097153
TI  - Activity-based process mining for clinical pathways computer aided design.
AB  - Current trends in health management improvement demand the standardization of
      care protocols to achieve better quality and efficiency. The use of Clinical
      Pathways is an emerging solution for that problem. However, current Clinical
      Pathways are big manuals written in natural language and highly affected by human
      subjectivity. These problems make the deployment and dissemination of them
      extremely difficult in real practice environments. In this work, a complete
      computer based architecture to help the representation and execution of Clinical
      Pathways is suggested. Furthermore, the difficulties inherent to the design of
      formal Clinical Pathways in this way requires new specific design tools to help
      making the system useful. Process Mining techniques can help to automatically
      infer processes definition from execution samples. Yet, the classical Process
      Mining paradigm is not totally compatible with the Clinical Pathways paradigm. In
      this paper, a pattern recognition algorithm based in an evolution of the Process
      Mining classical paradigm is presented and evaluated as a solution to this
      situation. The proposed algorithm is able to infer Clinical Pathways from
      execution logs to support the design of Clinical Pathways.

PMID- 21097154
TI  - Learning in glaucoma genetic risk assessment.
AB  - Genome Wide Association (GWA) studies are powerful tools to identify genes
      involved in common human diseases, and are becoming increasingly important in
      genetic epidemiology research. However, the statistical approaches behind GWA
      studies lack capability in taking into account the possible interactions among
      genetic markers; and true disease variants may be lost in statistical noise due
      to high threshold. A typical GWA study reports a few highly suspected signals,
      e.g. Single-nucleotide polymorphisms (SNPs), which usually account for a tiny
      portion of overall genetic risks for the disease of interest. This study proposes
      a computational learning approach in addition to parametric statistical methods
      along with a filtering mechanism, to build glaucoma genetic risk assessment
      model. Our data set was obtained from Singapore Malay Eye Study (SiMES),
      genotyped on Illumina 610 quad arrays. We constructed case-control data set with
      233 glaucoma and 458 healthy samples. A standard case-control association test
      was conducted on post-QC dataset with more than 500k SNPs. Genetic profile is
      constructed using genotype information from a list of 412 SNPs filtered by a
      relaxed pvalue threshold of 1 * 10(-3), and forms the feature space for learning.
      Among the five learning algorithms we performed, Support Vector Machines with
      radial kernel (SVM-radial) achieved the best result, with area under curve (ROC)
      of 99.4% and accuracy of 95.9%. The result illustrates that, learning approach in
      post GWAS data analysis is able to accurately assess genetic risk for glaucoma.
      The approach is more robust and comprehensive than individual SNPs matching
      method. We will further validate our results in several other data sets obtained
      in consequential population studies conducted in Singapore.

PMID- 21097155
TI  - Single nucleotide polymorphism selection using independent component analysis.
AB  - Bioinformatics research in genome wide association studies necessitates the
      development of algorithms capable of manipulating very-large datasets of Single
      Nucleotide Polymorphisms (SNP). To facilitate such association studies, we
      propose a novel framework for SNP selection using Independent Component Analysis
      (ICA). Compared to previous ICA-based methods, our framework works as a filtering
      technique to reduce the number of SNPs in a dataset, without the need for any
      class labels. We evaluate the proposed method by applying it on three published
      SNP datasets, and comparing the results to SNP selection methods based on
      Principal Component Analysis (PCA). Our results show the capability of ICA to
      capture an increased or matching amount of information from the datasets.

PMID- 21097156
TI  - Benchmarking of gene prediction programs for metagenomic data.
AB  - This manuscript presents the most rigorous benchmarking of gene annotation
      algorithms for metagenomic datasets to date. We compare three different programs:
      GeneMark, MetaGeneAnnotator (MGA) and Orphelia. The comparisons are based on
      their performances over simulated fragments from one hundred species of diverse
      lineages. We defined four different types of fragments; two types come from the
      inter- and intra-coding regions and the other types are from the gene edges. Hoff
      et al. used only 12 species in their comparison; therefore, their sample is too
      small to represent an environmental sample. Also, no predecessors has separately
      examined fragments that contain gene edges as opposed to intra-coding regions.
      General observations in our results are that performances of all these programs
      improve as we increase the length of the fragment. On the other hand, intra
      coding fragments of our data show low annotation error in all of the programs if
      compared to the gene edge fragments. Overall, we found an upper-bound performance
      by combining all the methods.

PMID- 21097157
TI  - A computationally fast measure of epistasis for 2 SNPs and a categorical
      phenotype.
AB  - Complex diseases may be caused by interactions or combined effects between
      multiple genetic and environmental factors. One of the main limitations of
      testing for interaction between genetic loci in large whole genome studies is the
      high computational cost of performing such analyses. In this study a new
      methodology for interaction testing (commonly referred to in genetics as the
      epistatic effect) between two single nucleotide polymorphisms (SNPs) and a
      categorical phenotype is presented. It is shown that it provides reasonable
      approximations with a significantly shorter run time. The proposed measure based
      on the Pearson's chi-square additive property is compared to fitting a logistic
      regression model on a randomly selected subset of 218 SNP loci from a study that
      included 550,000 SNPs). For each possible pair of SNPs a chi-square test for the
      epistatic effect on case-control status is estimated by fitting a logistic
      regression model, and compared to the results of the proposed method. Results
      indicate strong agreement (Pearson's correlation r>0.95) while the proposed
      method is found to be 20 times faster. This provides a significant pragmatic
      advantage for the proposed method since the number of tests for epistasis can now
      be increased by a factor of 20 while the computational cost remains the same.

PMID- 21097159
TI  - Polymerase chain reaction (PCR) and sequence specific oligonucleotide probes
      (SSOP) genotyping assay for detection of genes associated with rheumatoid
      arthritis and multiple sclerosis.
AB  - In this paper an assay for the detection of genes associated with rheumatoid
      arthritis (RA) and multiple sclerosis, using polymerase chain reaction (PCR) and
      sequence specific oligonucleotide probes (SSOP) is presented, in order to be
      further applied in a portable Lab-On-Chip (LOC) device. A substantial part of
      these reagents were based on the literature (11th International
      Histocompatibility Workshop, IHW), bearing the advantage of proven successful
      implementation in genotyping, while others were designed for this study. More
      precisely, our methodology discriminates HLA-DRB1 as DRB1*01, *04 and *10, which
      include shared epitope (SE) alleles associated with RA and additionally DRB1*15
      allele, including DRB1*1501 associated with MS (broad genotyping method). To
      further present the basic elements of the assay for high resolution genotyping of
      SE DRB1 alleles, we provide as an example the case of HLA-DRB1*10 alleles
      (HLADRB1* 100101, *100102, *100103, *1002 and *1003). Regarding the methodology
      for developing a detection assay, for SNPs associated with RA or MS the basic
      steps are presented. DNA sequence data are obtained from IMGT/HLA and SNP
      database. Online software tools are used to define hybridization specificity of
      primers and probes towards human DNA, leading to hybridization patterns that
      uniquely designate a target allele and evaluate parameters influencing PCR
      efficiency. Respecting current technological limitations of autonomous molecular
      based LOC systems the approach of broad genotyping of HLA-DRB1*01/*04/*10/*15
      genes, is intended to be initially used, leaving, high resolution genotyping of
      SE alleles for future implementations. This method is easy to be updated and
      extended to detect additional associated loci with RA or MS.

PMID- 21097158
TI  - Regulatory network of microRNAs in RAW 264.7 macrophage cells.
AB  - microRNAs (miRNA) play important roles in regulating immunity. Here we utilize
      the systems biology approach to predict the regulatory network of miRNAs among
      the most down-regulated genes by the lipopolysaccharides (LPS) treatment in the
      macrophage RAW267.4 cell line. We combine the proteome and transcriptome data
      sets to define 200 target genes that are significantly down-regulated by the LPS
      treatment. We perform the profiling of over 300 miRNAs with the RNA-Seq method.
      Using the complementary binding rule between the seed sequences of profiled
      miRNAs and the 3'UTRs of target genes, we predict genes involved in mobility,
      metabolism, and oxidative phosphorylation as the top targets of miRNA negative
      regulation.

PMID- 21097160
TI  - Peripheral nerve signal recording and processing for artificial limb control.
AB  - In order to take full advantage of modern multiple-degree of freedom prosthetic
      limbs, robust and natural control signals are needed. Previous work has shown
      that beamforming provides a method to extract such signals from peripheral nerve
      activity [1]. This paper describes in vivo experiments done to validate that
      method in a more realistic case. A 16-channel Flat Interface Nerve Electrode was
      used to record from the Sciatic nerve in Rabbit, while the distal Tibial and
      Peroneal branches were stimulated. Beamforming provided R(2)=0.7 +/- 0.2, an
      improvement of 0.12 +/- 0.06 over the a posteriori chosen best channels. When
      more realistic signals were generated using kHz-level stimulation, the
      beamforming filters were able to distinguish which branch was being stimulated,
      and in many cases how strongly, over a large range of stimulation intensities.

PMID- 21097161
TI  - Epileptic seizure onset detection prior to clinical manifestation.
AB  - In this paper, we present the design of an epilepticseizure detector. This
      circuit is part of an implantable device used to continuously record
      intracerebral electroencephalographic signals through subdural and depth
      electrodes. The implemented seizure detector is based on a detection algorithm
      validated in Matlab tools and the circuits were implemented using CMOS 0.18
      microm process. The proposed system was tested using intracerebral EEG recordings
      from two patients with drug-resistant epilepsy. Four seizures were assessed by
      the proposed CMOS building blocks and the required delays to detect these
      seizures were 3, 8, 11, and 11 sec, respectively after electric onset. The
      simulated total power consumption of the detector was 6.71 microW. Together,
      these preliminary results indicate the possibility of building implantable ultra
      low power seizure-detection devices.

PMID- 21097162
TI  - Development of an implantable transverse intrafascicular multichannel electrode
      (TIME) system for relieving phantom limb pain.
AB  - Phantom limb pain frequently follows amputation. Currently there is no fully
      effective treatment available. Our aim is to develop an innovative Human Machine
      Interface (HMI) where we apply multi-channel microstimulation to the nerve stump
      of an amputee subject to manipulate the phantom limb sensations and explore the
      possibility of using microstimulation as a treatment for phantom limb pain.

PMID- 21097163
TI  - Wireless distributed architecture for therapeutic functional electrical
      stimulation: a technology to design network-based muscle control.
AB  - This paper presents a distributed Functional Electrical Stimulation architecture
      based on a wireless network, for therapeutic training of disabled patients. On
      this distributed architecture, a global controller can pilot a set of stimulation
      and acquisition units and modify dynamically stimulation and acquisition
      parameters. This solution intend to be a tool for researchers and therapist to
      develop closed-loop control algorithms and strategies for therapeutic
      rehabilitation applications with external FES, in a clinical context. In a
      wireless networkbased control, the variable delay introduced by the network must
      be taken into account to ensure the stability of the closed loop. Thus, in order
      to characterize the medium on which the control is performed, we carried out
      accurate measurements of the architecture performances (stack-crossing, round
      trip time, etc.).

PMID- 21097164
TI  - Command of an upper extremity FES system using a simple set of commands.
AB  - The purpose of this project is to develop a method of providing a complete set of
      movement commands to an upper extremity neuroprosthesis when the number of
      command signals available is fewer than required by the mechanical system. The
      functional relevance of the developed command interface will be tested in a
      virtual reality environment, where users-able bodied and paralyzed-will use a
      limited number of commands to control a simulated neuroprosthesis capable of
      executing a set of important daily activities that require coordinated motion of
      a larger number of mechanical degrees of freedom.

PMID- 21097165
TI  - Interleaved multichannel epimysial stimulation for eliciting smooth contraction
      of muscle with reduced fatigue.
AB  - Functional electrical stimulation (FES) refers to the method by which sensory or
      motor functionality is restored through the use of coordinated stimulation of
      tissue. Our group has developed a mechanically conformable multielectrode array
      (cMEA) that can stimulate and record from the surface of muscles with high
      fidelity and low invasiveness, making the device well suited for various FES
      applications. The research presented here investigates the feasibility of using a
      cMEA to deliver asynchronous spatiotemporal stimulation patterns epimysially (on
      the surface of muscles). Specifically, we employ an interleaved stimulation
      protocol to achieve force responses with less fatigue and less ripple than those
      produced by standard simultaneous stimulation protocols delivered at high and low
      frequencies, respectively. This experimentation demonstrates that asynchronous
      spatiotemporal stimulation protocols delivered epimysially via a cMEA can improve
      the characteristics of the resulting force profiles.

PMID- 21097166
TI  - Molecular photovoltaic structures for optical activation of excitable cells:
      current advances and perspectives.
AB  - Current neural stimulation devices for the treatment of sensory and motor
      disorders are based on electrical stimulation. Using this technique, neural
      activity is triggered by electrical stimuli applied through electrodes in contact
      with the cells. Due to physical constraints of the electrodes the spatial control
      of stimulation is limited, which in some cases generates unwanted side effects.
      In addition, adverse tissue reactions occur after long term contact with the
      electrodes. A potential solution is the application of methods based on light
      instead of electrical energy, in which the electrical stimulator and the
      electrode are replaced by a light source and an optical fiber. Although optical
      stimulation approaches that allow spatially selective, highly specific and
      contact-free control of the neural activity have been developed in recent years,
      their implementation requires genetic manipulation, limiting the perspectives for
      clinical applications. A molecular photovoltaic structure potentially able to
      mediate light-induced cellular responses without involving genetic modification
      is the photosynthetic pigment-protein complex Photosystem I (PSI). In this work,
      the recent advances on the application of PSI reaction centers for optical
      control of cellular activity are presented. Perspectives of application of PSI
      reaction centers in the development of future methods for clinical neural
      stimulation are also presented.

PMID- 21097167
TI  - A wearable system for the visually impaired.
AB  - We present a light-weight, cheap and low-power, wearable system for assisting the
      visually impaired in performing routine mobility tasks. Our system extends the
      range of the white cane by providing the user with vibro-tactile cues
      corresponding to the location of obstacles and a safe path for traversal through
      a cluttered environment. The presented approach keeps cognitive load to a
      minimum, and while being autonomous, adapts to the changing mobility requirements
      of a navigating user. In this paper, we provide an overview of the hardware and
      algorithmic components of our system, and show results of pilot studies with
      human test subjects. Our system operates at 20Hz, and significantly improves
      mobility performance compared to using only the white cane.

PMID- 21097168
TI  - Reconstruction of cortical sources activities for online classification of
      electroencephalographic signals.
AB  - We compare the results given by different methods to reconstruct cortical sources
      activity in order to classify EEG in real time. Two motor imagery experiments
      were performed. The aim was to retrieve from 1-second windows of signal which
      motor imagery task the subjects were performing. The use of cortical activity
      reconstruction was compared to Laplacian filtering, which is often used in BCI. A
      recursive algorithm using Student's t-test was used to select relevant cortical
      sources. The Beamformer method led to an improvement of the classification for
      the first experiment, which included six motor imagery tasks. The weighted
      Minimum-Norm method required the use of a specific head model, extracted from the
      subject's MRI, to improve the classification. It then gave the best results on
      the second experiment, achieving a classification rate of 77% compared to 71% for
      direct use of electrode data and 75% for Laplacian filtering and Beamformer.

PMID- 21097169
TI  - On improvement of detection of Obstructive Sleep Apnea by partial least square
      based extraction of dynamic features.
AB  - This paper presents a methodology for Obstructive Sleep Apnea (OSA) detection
      based on the HRV analysis, where as a measure of relevance PLS is used. Besides,
      two different combining approaches for the selection of the best set of contours
      are studied. Attained results can be oriented in research focused on finding
      alternative methods minimizing the HRV-derived parameters used for OSA
      diagnosing, with a diagnostic accuracy comparable to a polysomnogram. For two
      classes (normal, apnea) the results for PLS are: specificity 90%, sensibility 91%
      and accuracy 93.56%.

PMID- 21097170
TI  - A Bayesian approach for epileptic seizures detection with 3D accelerometers
      sensors.
AB  - In this paper, an algorithm able to detect epilepsy seizure based on 3D
      accelerometers and with patient adaptation is presented. This algorithm is based
      on a Bayesian approach using hidden Markov models for statistical modelling of
      moves signals. A particular focus is set on the learning procedure and in
      particular on its initialisation to ensure a good learning and to avoid numerical
      instability. Numerical simulations show that, without inhibition of the detection
      algorithm when the person is standing up, the algorithm is able to detect close
      to 90% of seizures when false alarms are 25% of alarms.

PMID- 21097172
TI  - A wavelet approach for unsupervised nystagmus analysis on ENG and VOG recordings.
AB  - Several algorithms are available to quantify nystagmus beats in electro
      nystagmography (ENG) and videooculography (VOG) recordings. These algorithms use
      parameterized approaches to detect the fast components of nystagmus beats. This
      paper proposes a wavelet approach to detect fast components of nystagmus beats.
      The main advantage of this approach compared to alternatives, is the completely
      unsupervised automated routine. The algorithm is implemented and validated in
      different clinical experiments. The results are compared to that of an
      alternative parameterized technique. Results show that the wavelet approach is
      suitable for automated nystagmus analysis.

PMID- 21097171
TI  - A comparison of different dimensionality reduction and feature selection methods
      for single trial ERP detection.
AB  - Dimensionality reduction and feature selection is an important aspect of
      electroencephalography based event related potential detection systems such as
      brain computer interfaces. In our study, a predefined sequence of letters was
      presented to subjects in a Rapid Serial Visual Presentation (RSVP) paradigm. EEG
      data were collected and analyzed offline. A linear discriminant analysis (LDA)
      classifier was designed as the ERP (Event Related Potential) detector for its
      simplicity. Different dimensionality reduction and feature selection methods were
      applied and compared in a greedy wrapper framework. Experimental results showed
      that PCA with the first 10 principal components for each channel performed best
      and could be used in both online and offline systems.

PMID- 21097173
TI  - Examining the adverse effects of limb position on pattern recognition based
      myoelectric control.
AB  - Pattern recognition of myoelectric signals for the control of prosthetic devices
      has been widely reported and debated. A large portion of the literature focuses
      on offline classification accuracy of pre-recorded signals. Historically,
      however, there has been a semantic gap between research findings and a clinically
      viable implementation. Recently, renewed focus on prosthetics research has pushed
      the field to provide more clinically relevant outcomes. One way to work towards
      this goal is to examine the differences between research and clinical results.
      The constrained nature in which offline training and test data is often collected
      compared to the dynamic nature of prosthetic use is just one example. In this
      work, we demonstrate that variations in limb position after training can have a
      substantial impact on the robustness of myoelectric pattern recognition.

PMID- 21097174
TI  - A computational environment for long-term multi-feature and multi-algorithm
      seizure prediction.
AB  - The daily life of epilepsy patients is constrained by the possibility of
      occurrence of seizures. Until now, seizures cannot be predicted with sufficient
      sensitivity and specificity. Most of the seizure prediction studies have been
      focused on a small number of patients, and frequently assuming unrealistic
      hypothesis. This paper adopts the view that for an appropriate development of
      reliable predictors one should consider long-term recordings and several features
      and algorithms integrated in one software tool. A computational environment,
      based on Matlab ((r)), is presented, aiming to be an innovative tool for seizure
      prediction. It results from the need of a powerful and flexible tool for long
      term EEG/ECG analysis by multiple features and algorithms. After being extracted,
      features can be subjected to several reduction and selection methods, and then
      used for prediction. The predictions can be conducted based on optimized
      thresholds or by applying computational intelligence methods. One important
      aspect is the integrated evaluation of the seizure prediction characteristic of
      the developed predictors.

PMID- 21097175
TI  - Three-dimensional gesture comparison using curvature analysis of position and
      orientation.
AB  - This paper describes a new analysis method dedicated to the comparison of human
      gestures. The orientations and the positions of the gestures are first digitized
      using active 3D sensors and then compared to a 6-D template using curvature
      analysis. The proposed algorithm first starts by computing the invariant
      curvature of 3D position and orientation of a surgical tool using Frenet-Serret
      frames in 3D and quaternion space. The resulting curvature calculation is matched
      and compared to the template using a Dynamic Time Warping method. The proposed
      method is invariant to sensor position and orientation. An experimental study
      shows the efficiency of the new algorithm for an application in obstetrics, where
      the aim is to compare forceps blade placements between a senior medical doctor
      and a novice.

PMID- 21097176
TI  - A new apparatus for analysis of viscoelastic fluids by ultrasound radiation
      force.
AB  - The acoustic radiation force has been used as the method to examine the physical
      properties of materials in several areas. Vibro-acoustography is an acoustic
      radiation force technique that is being used to perform analysis of mechanical
      properties of materials. In this application a focused acoustic modulated force
      excites target which vibrates at the frequency of modulation. The emitted sound
      is characteristic of the medium mechanical impedance and it is measured using a
      dedicated hydrophone. In this paper, we propose a modification of the vibro
      acoustography (VAG) technique and apply a technique called vibro
      acustomagnetography (VAMG) by replacing the hydrophone by a magnetic sensor with
      high sensitivity. In this case, the modulated acoustic radiation will be applied
      on a magnetized target immersed in the fluid under study. With this procedure,
      static and dynamic displacement of the magnetic target (ball) will be measured
      when acoustically excited. In this study, we used a magnetoresistive sensor with
      resolution of about nT for mounting the transducer to detect displacement of the
      magnetic target. The vibration of the target was induced by a non-contact force,
      using an ultrasonic beam modulated by two concentric beams generated by confocal
      piezoelectric elements with equal area and common focus to 7 cm. The target used
      was a magnetic sphere of NdFeB with a radius of 2.36 mm. The apparatus was
      evaluated through of measurements in water and oil. Viscoelastic parameters were
      estimated fitting the nonlinear response of the magnetic transducer function of
      frequency modulation.

PMID- 21097177
TI  - Ultrasonic array of thick film transducers for biological tissue
      characterization.
AB  - The initial motivation for this work was to accomplish an easy way to manufacture
      different geometries of ultrasonic transducers and arrays using a PZT powder,
      combined with a standard process to have repetitive series of them. The
      piezoelectric thick film was obtained using a PZT paste and applying it by screen
      printing on an alumina substrate. Then, the film was drying and sintered with a
      temperature-time profile determined by the paste characteristics. Each transducer
      is composed by three layers, one by PZT and two acting as electrodes. The active
      element of the paste is a PZT powder which is dispersed in a commercial vehicle
      to obtain rheological properties suitable for use the screen printing process.
      The connection between PZT particles is improved by adding a lead borosilicate
      frit glass that also helps to attach the film to the substrate due to the
      relatively low temperature of sintered that has been used in this process. The
      PZT film has low density that is generated by internal porosity, so its acoustic
      impedance is lower than for a bulk ceramic transducer and so is well adapted to
      testing human tissues. At the same time the thick film technology is well suited
      to make medium size transducers and also arrays performed with tiny ultrasonic
      transducers.

PMID- 21097178
TI  - A low-power high-performance accelerometer ASIC for high-end medical motion
      sensing.
AB  - A 170uW readout IC for a capacitive MEMS acceleration sensor was implemented in a
      1.5V 0.13um CMOS for high-end medical motion sensing applications. The
      accelerometer achieves a 45ug/vHz noise floor and a dynamic range larger than
      87dB for a 400Hz bandwidth. Power reduction is achieved by introducing reset and
      common-mode feedback circuit techniques based on a non-unity-gain feedback
      configuration.

PMID- 21097179
TI  - An experimental measurement complex for probable estimation of arterial
      stiffness.
AB  - Current work is a part of long term research, which aim is to study the
      possibilities to diagnose the atherosclerosis in early stadium by using pulse
      wave velocity and its waveform analysis. The mobile experimental measurement
      complex is built and technically tested for the long term study in hospital.
      Measurement complex consists of ten physiological signal recording channels and
      reference devices: Sphygmocor, Arteriograph, Finapres. The measurements with this
      complex are planned to carry out during six month on patients with different
      severity of coronary disease and diabetes.

PMID- 21097180
TI  - Ambient Assisted Nutritional Advisor for elderly people living at home.
AB  - Nutrition is a critical aspect when getting older because bad nutrition habits
      can accelerate the process of degradation of the physical condition of the old
      person. In order to mitigate this problem, an Ambient Assisted Living service has
      been developed. Research with this service is focused on demonstrating that with
      an Ambient Intelligence systems it is possible to make the nutritional management
      much more effective by influencing the user, by automatically and seamlessly
      monitoring and by facilitating tools for nutritional management for people that
      want to be autonomous. In this paper both requirement acquisition and development
      processes are described as well.

PMID- 21097181
TI  - A subject state detection approach to determine rest-activity patterns using load
      cells.
AB  - A patient's sleep/wake schedule is an important step underlying clinical
      evaluation of sleep-related complaints. Aspects related to timing of a person's
      sleep routine provide important clues regarding diagnosis and treatments.
      Solutions for sleep complaints may sometimes rely solely on changes in habits and
      life style, based on what is learned from daily rest-activity patterns. This
      paper describes an approach for determining two states, in-bed and out-of-bed,
      using load cells under the bed. These states are important because they can help
      characterize rest-activity patterns at nighttime or detect bed exits in hospitals
      or nursing homes. The information derived from the load cells is valuable as an
      objective and continuous measure of daily patterns, and it is particularly
      valuable in sleep studies in populations who would not be able to remember
      specific hours to complete sleep diaries. The approach is evaluated on data
      collected in a laboratory experiment, in a sleep clinic, and also on data
      collected from residents of an assisted-living facility.

PMID- 21097182
TI  - Information and assistance bubbles to help elderly people in public environments.
AB  - Ambient Assisted Living (AAL) is an emerging bundle of technologies and services
      that has been specially conceived to support disabled and elderly people to be
      more autonomous in their daily life. Support for mobility is a key aspect in AAL,
      and makes elderly people feel very independent and socially integrated. This
      paper describes an AAL solution to support elderly people outside home: provides
      information and assistance at the street near public buildings, and inside public
      buildings. The concept of bubble is proposed in this paper as a physical space
      where it is possible to consume to a number of local services. Presented mobility
      based AAL Services are integrated with an ambient assisted home, so users
      perceive mobility service as an extension of the care chain beyond the boundaries
      of their homes.

PMID- 21097183
TI  - Virtual worlds to enhance Ambient-Assisted Living.
AB  - In this paper we discuss about the integration of Ambient-Assisted Living (AAL)
      with virtual worlds. The integration of sensors from the AAL environment (e.g.
      vital signs, motion sensors) in the Virtual World can enhance the provision of in
      world eHealth services, such as tele-rehabilitation, and taking advance of the
      social nature of virtual worlds. An implementation of a virtual world integrated
      in an AAL environment for tele-rehabilitation is described in this paper. At this
      time, all of the system's modules have been developed and we are currently
      integrating them in a fully functional version. The system will be tested with
      real users during 2010 in the Sport Medical Unit of The University of Seville.
      This paper describes the architecture and functionalities of the system.

PMID- 21097184
TI  - Home healthcare settop-box for senior chronic care using ISO/IEEE 11073 PHD
      standard.
AB  - As the number of seniors with chronic disease increases, the need of home
      healthcare settop-box is increased to manage their chronic disease in their home
      environment. Using the home healthcare settop-box, the patients can regularly
      check their health data, and finally, it can lead the decrease of medical
      expenses. For the home healthcare settop-box, the most important factor is the
      standard compatibility, which can interoperate with standard devices of any other
      companies. In this paper, we propose a home healthcare settop-box using ISO/IEEE
      11073 PHD standard. It collects health data according to the PHD standard, and
      provides a chronic-care service based on the collected data. The proposed settop
      box is connected with 3 devices of weigh scale, blood pressure monitor, and
      glucose meter, and tested at 10 homes for a month. Lastly, the proposed settop
      box can be used for various healthcare services such as Google Health and
      Telemedicine Services using a healthcare platform server.

PMID- 21097185
TI  - Automatic characterization and detection of behavioral patterns using linear
      predictive coding of accelerometer sensor data.
AB  - In this study, we target to automatically detect behavioral patterns of patients
      with autism. Many stereotypical behavioral patterns may hinder their learning
      ability as a child and patterns such as self-injurious behaviors (SIB) can lead
      to critical damages or wounds as they tend to repeatedly harm one single
      location. Our custom designed accelerometer based wearable sensor can be placed
      at various locations of the body to detect stereotypical self-stimulatory
      behaviors (stereotypy) and self-injurious behaviors of patients with Autism
      Spectrum Disorder (ASD). A microphone was used to record sounds so that we may
      understand the surrounding environment and video provided ground truth for
      analysis. The analysis was done on four children diagnosed with ASD who showed
      repeated self-stimulatory behaviors that involve part of the body such as
      flapping arms, body rocking and self-injurious behaviors such as punching their
      face, or hitting their legs. The goal of this study is to devise novel algorithms
      to detect these events and open possibility for design of intervention methods.
      In this paper, we have shown time domain pattern matching with linear predictive
      coding (LPC) of data to design detection and classification of these ASD
      behavioral events. We observe clusters of pole locations from LPC roots to select
      candidates and apply pattern matching for classification. We also show novel
      event detection using online dictionary update method. We show that our proposed
      method achieves recall rate of 95.5% for SIB, 93.5% for flapping, and 95.5% for
      rocking which is an increase of approximately 5% compared to flapping events
      detected by using wrist worn sensors in our previous study.

PMID- 21097186
TI  - Clip-on wireless wearable microwave sensor for ambulatory cardiac monitoring.
AB  - We present a new type of non-contact sensor for use in ambulatory cardiac
      monitoring. The sensor operation is based on a microwave Doppler technique;
      however, instead of detecting the heart activity from a distance, the sensor is
      placed on the patient's chest over the clothing. The microwave sensor directly
      measures heart movement rather than electrical activity, and is thus
      complementary to ECG. The primary advantages of the microwave sensor includes
      small size, light weight, low power, low-cost, and the ability to operate through
      clothing. We present a sample sensor design that incorporates a 2.4 GHz Doppler
      circuit, integrated microstrip patch antenna, and microntroller with 12-bit ADC
      data sampling. The prototype sensor also includes a wireless data link for
      sending data to a remote PC or mobile phone. Sample data is shown for several
      subjects and compared to data from a commercial portable ECG device. Data
      collected from the microwave sensor exhibits a significant amount of features,
      indicating possible use as a tool for monitoring heart mechanics and detection of
      abnormalities such as fibrillation and akinesia.

PMID- 21097187
TI  - Performance evaluation of wearable wireless body area networks during walking
      motions in 444.5 MHz and 2450 MHz.
AB  - This paper gives performance evaluation of wearable wireless body area networks
      (WBANs) during walking motion. In order to evaluate the performance, received
      signal strength (RSS), packet error rate (PER), and bit error rate (BER) are
      measured in an anechoic chamber and an office room. This measurement is conducted
      in the frequency band of 444.5 and 2450 MHz by using GFSK signal with symbol rate
      of 1 MHz. The results show that in the anechoic chamber the WBAN using the 444.5
      MHz enables to provide error-free communication, on the other hand, the WBAN
      operated in the 2450 MHz faces packet errors. Measurement results in the office
      room give comparable performance between these frequencies. From these
      observations, the use of 2450 MHz for wearable WBANs needs reflection waves in
      order to compensate a shadowing effect caused by the human body using the WBAN.

PMID- 21097188
TI  - Design and realization of a wireless sensor gateway for health monitoring.
AB  - This paper describes the design and realization of a wireless sensor gateway
      (WSG) within a wireless sensor network (WSN) for health monitoring. The WSN
      allows recording and wireless transmission of biosignals, namely the
      electrocardiogram, pulse wave and body weight, which are important parameters for
      cardiovascular monitoring. These can be displayed, analysed, and saved on the WSG
      through a user interface based on a touch screen. The proposed WSG has the
      distinctive feature of using two different radio transceivers, exploiting the
      advantages of each device. Currently, most personal computers and handhelds have
      standardized Bluetooth interfaces (IEEE 802.15.1) but not ZigBee interfaces (IEEE
      802.15.4). Hence, the proposed gateway is designed to receive data from wireless
      sensors through its ZigBee interface and to forward them to a personal computer
      via its Bluetooth interface. This feature, combined with simple touch screen menu
      navigation will reach increased patient compliance and consequently increased
      benefit for patient in terms of healthcare and safety.

PMID- 21097189
TI  - Multilayer limb quasi-static electromagnetic modeling with experiments for
      Galvanic coupling type IBC.
AB  - Intra-body communication (IBC) is a new, emerging, short-range and human body
      based communication methodology. It is a technique to network various devices on
      human body, by utilizing the conducting properties of human tissues. For
      currently fast developed Body area network(BAN)/Body sensor network(BSN), IBC is
      believed to have advantages in power consumption, electromagnetic radiation,
      interference from external electromagnetic noise, security, and restriction in
      spectrum resource. In this article, the authors propose an improved mathematical
      model, which includes both electrical properties and proportion of human tissues,
      for IBC on a human limb. By solving the mathematical model analytically on four
      layer system (skin, fat, muscle, and bone) and conducting in-vivo experiment, a
      comparison has been conducted.

PMID- 21097190
TI  - A headband for classifying human postures.
AB  - a real-time method using only accelerometer data is developed for classifying
      basic human static postures, namely sitting, standing, and lying, as well as
      dynamic transitions between them. The algorithm uses discrete wavelet transform
      (DWT) in combination with a fuzzy logic inference system (FIS). Data from a
      single three-axis accelerometer integrated into a wearable headband is
      transmitted wirelessly, collected and analyzed in real time on a laptop computer,
      to extract two sets of features for posture classification. The received
      acceleration signals are decomposed using the DWT to extract the dynamic
      features; changes in the smoothness of the signal that reflect a transition
      between postures are detected at finer DWT scales. FIS then uses the previous
      posture transition and DWT-extracted features to determine the static postures.

PMID- 21097191
TI  - DIORAMA: dynamic information collection and resource tracking architecture.
AB  - DIORAMA is a real-time scalable decision support framework built on rapid
      information collection and accurate resource tracking functionalities. Using RFID
      technology the proposed system tracks emergency responders and victims at the
      disaster scene. DIORAMA improves the accuracy and decreases the time it takes
      rescuers to triage, treat and evacuate victims from a disaster scene, as compared
      to the traditional methods and process that involves using paper triage tags. The
      information can then be viewed from a website that shows a satellite image of the
      disaster area with icons representing the paramedics and victims.

PMID- 21097192
TI  - On the use of Augmented Reality techniques in learning and interpretation of
      cardiologic data.
AB  - Augmented Reality is a technology which provides people with more intuitive ways
      of interaction and visualization, close to those in real world. The amount of
      applications using Augmented Reality is growing every day, and results can be
      already seen in several fields such as Education, Training, Entertainment and
      Medicine. The system proposed in this article intends to provide a friendly and
      intuitive interface based on Augmented Reality for heart beating evaluation and
      visualization. Cardiologic data is loaded from several distinct sources: simple
      standards of heart beating frequencies (for example situations like running or
      sleeping), files of heart beating signals, scanned electrocardiographs and real
      time data acquisition of patient's heart beating. All this data is processed to
      produce visualization within Augmented Reality environments. The results obtained
      in this research have shown that the developed system is able to simplify the
      understanding of concepts about heart beating and its functioning. Furthermore,
      the system can help health professionals in the task of retrieving, processing
      and converting data from all the sources handled by the system, with the support
      of an edition and visualization mode.

PMID- 21097193
TI  - EEG compression using JPEG2000: how much loss is too much?
AB  - Compression of biosignals is an important means of conserving power in wireless
      body area networks and ambulatory monitoring systems. In contrast to lossless
      compression techniques, lossy compression algorithms can achieve higher
      compression ratios and hence, higher power savings, at the expense of some
      degradation of the reconstructed signal. In this paper, a variant of the lossy
      JPEG2000 algorithm is applied to Electroencephalogram (EEG) data from the
      Freiburg epilepsy database. By varying compression parameters, a range of
      reconstructions of varying signal fidelity is produced. Although lossy
      compression has been applied to EEG data in previous studies, it is unclear what
      level of signal degradation, if any, would be acceptable to a clinician before
      diagnostically significant information is lost. In this paper, the reconstructed
      EEG signals are applied to REACT, a state-of-the-art seizure detection algorithm,
      in order to determine the effect of lossy compression on its seizure detection
      ability. By using REACT in place of a clinician, many hundreds of hours of
      reconstructed EEG data are efficiently analysed, thereby allowing an analysis of
      the amount of EEG signal distortion that can be tolerated. The corresponding
      compression ratios that can be achieved are also presented.

PMID- 21097194
TI  - Analysis of Magnetic Resonance Spectroscopic signals with data-based
      autocorrelation wavelets.
AB  - A new class of wavelet functions called data-based autocorrelation wavelets is
      developed for analyzing Magnetic Resonance Spectroscopic (MRS) signals by means
      of the continuous wavelet transform (CWT), instead of the traditional wavelet
      like Morlet wavelet. These new wavelets are derived from the normalized
      autocorrelation function from metabolite data and then used for detecting the
      presence of a given metabolite in a signal with a presence of many different
      components and finally for quantifying some of its parameters.

PMID- 21097195
TI  - Respiration-induced changes in ear photoplethysmography relates to relative blood
      volume during hemodialysis.
AB  - Renal failure patients provide a good model of fluid overload with the process of
      hemodialysis leading to central hypovolemia. This study aims to assess if
      hemodialysis induces identifiable changes in ear photoplethysmographic waveform
      variability (PPGV). The results are based on data collected from 10 kidney
      failure patients undergoing regular hemodialysis; classified as either fluid
      removal or non-fluid removal patients. Six minutes of continuous
      photoplethysmography (PPG) signals were recorded at pre-dialysis, end of dialysis
      and at regular intervals of 20 minutes during hemodialysis. Baseline and
      amplitude variabilities were derived from the PPG waveform. Frequency spectrum
      analysis was applied to these variability signals and spectral powers were then
      calculated from low frequency (LF), mid frequency (MF) and high frequency (HF)
      bands. The results indicate that in fluid removal patients, LF (p = 0.04), MF (p
      = 0.03) and HF (p = 0.0003) powers of amplitude ear PPGV (expressed in mean
      scaled units) showed a significant increase at the end of dialysis compared to
      pre-dialysis. No significant change was observed in non-fluid removal patients. A
      moderate correlation was found between relative blood volume (RBV) and HF power
      (median R = 0.64, p < 0.05). This study suggests that ear PPG may be a suitable
      monitor of the systemic circulation and can provide a non-invasive tool to detect
      blood volume loss.

PMID- 21097196
TI  - Real-time automatic switching between noise suppression algorithms for deployment
      in cochlear implants.
AB  - Cochlear implant patients often complain about their difficulty in understanding
      speech in noisy environments. Currently a fixed noise suppression algorithm is
      used in cochlear implants regardless of the characteristics of the speech or
      noise environment. Access to an intelligent mechanism to determine the noise
      environment on-the-fly in order to automatically switch between different noise
      suppression algorithms in real-time can enhance patients experience with cochlear
      implants. In this paper, we report the first prototype system implementing such a
      real-time switching mechanism for automatic selection between two noise
      suppression algorithms designed for two commonly encountered noisy environments.
      The results obtained indicate the feasibility of this on-the-fly switching for
      actual deployment in cochlear implants.

PMID- 21097197
TI  - A real-time weighted-eigenvector MUSIC method for time-frequency analysis of
      electrogastrogram slow wave.
AB  - The surface electrogastrogram (EGG) records the electrical slow wave of the
      stomach noninvasively, whose frequency is a useful clinical indicator of the
      state of gastric motility. Estimators based on the periodogram method are widely
      adopted to obtain this parameter. But they are with a poor frequency domain
      resolution when the data window is short in time-frequency analysis, and have not
      taken full advantage of the slow wave model. We present a modified multiple
      signal classification (MUSIC) method for computing the frequency from surface EGG
      records, developing it into a real-time time-frequency analysis algorithm.
      Simulations indicate that the modified MUSIC method has better performance in
      resolution and precision in the sinusoid-like resultant signal frequency
      detecting than periodogram. Volunteer data tests show that the modified MUSIC
      method is stable and efficient for clinical applications, and reduces the danger
      of pseudo peaks for the diagnosis.

PMID- 21097198
TI  - High-resolution cardiac MRI using partially separable functions and weighted
      spatial smoothness regularization.
AB  - Imaging of cardiac morphology and functions in high spatiotemporal resolution
      using MRI is a challenging problem due to limited imaging speed and the inherent
      tradeoff between spatial resolution, temporal resolution, and signal-to-noise
      ratio (SNR). The partially separable function (PSF) model has been shown to
      achieve high spatiotemporal resolution but can lead to noisy reconstructions.
      This paper proposes a method to improve the SNR and reduce artifacts in PSF-based
      reconstructions through the use of anatomical constraints. These anatomical
      constraints are obtained from a high-SNR image of composite (k, t)-space data
      (summed along the time axis) and used to regularize the PSF reconstruction. The
      method has been evaluated on experimental data of rat hearts to achieve 390
      epsilonm in-plane resolution and 15 ms temporal resolution.

PMID- 21097199
TI  - Improved compressed sensing MRI with multi-channel data using reweighted l(1)
      minimization.
AB  - Compressed sensing (CS) is an emerging technology to speed up magnetic resonance
      imaging (MRI). Since most clinical MRI scanners are equipped with multi-channel
      receiver systems, there has been a number of works to integrate CS with multi
      channel systems. In this paper, we propose a method that extends the reweighted
      l(1) minimization to the CS MRI with multi-channel data. The simulated
      experimental results show that the new method can provide improved reconstruction
      quality.

PMID- 21097200
TI  - Non-iterative relative bias correction for 3D reconstruction of in utero fetal
      brain MR imaging.
AB  - The slice intersection motion correction (SIMC) method is a powerful tool to
      compensate for motion that occurs during in utero acquisition of the multislice
      magnetic resonance (MR) images of the human fetal brain. The SIMC method makes
      use of the slice intersection intensity profiles of orthogonally planned slice
      pairs to simultaneously correct for the relative motion occurring between all the
      acquired slices. This approach is based on the assumption that the bias field is
      consistent between slices. However, for some clinical studies where there is a
      strong bias field combined with significant fetal motion relative to the coils,
      this assumption is broken and the resulting motion estimate and the
      reconstruction to a 3D volume can both contain errors. In this work, we propose a
      method to correct for the relative differences in bias field between all slice
      pairs. For this, we define the energy function as the mean square difference of
      the intersection profiles, that is then minimized with respect to the bias field
      parameters of the slices. A non iterative method which considers the relative
      bias between each slice simultaneously is used to efficiently remove
      inconsistencies. The method, when tested on synthetic simulations and actual
      clinical imaging studies where bias was an issue, brought a significant
      improvement to the final reconstructed image.

PMID- 21097201
TI  - Correction of field inhomogeneity effects on limited k-space MRSI data using
      anatomical constraints.
AB  - Magnetic field inhomogeneity is a long-standing problem in magnetic resonance
      imaging (MRI) and spectroscopic imaging (MRSI). Specifically, in MRSI, field
      inhomogeneity, if not corrected, can cause frequency shifts, line broadening, and
      lineshape distortions in the spectral peaks. This paper addresses the problem of
      correcting the field inhomogeneity effects on limited k-space MRSI data. A
      penalized maximum-likelihood method is proposed, which enables the use of
      anatomical constraints for improving the correction performance with only limited
      k-space data. Simulation results are shown to demonstrate the effectiveness of
      the proposed method.

PMID- 21097202
TI  - Study of the magnetic interaction of a 4-coil array and copper shielding with a
      PET/MRI using the finite-element method.
AB  - The effect of the shielding in a PET-MRI system was numerically estimated by
      calculating the RF magnetic field, B1, produced by a coil array of 4 independent
      elements at the resonant frequency of 171 MHz (4T for protons). The array coil is
      located inside a MUPET camera to simultaneously acquire PET and MR images of a
      rat brain. Profiles showed a good uniformity despite the shielding that is
      interacting between the coil array and the MUPET camera. These limitations are
      currently being dealt with the fabrication of a birdcage coil design.

PMID- 21097203
TI  - Monitoring voltage-sensitive membrane impedance change using radio frequency
      interrogation.
AB  - Here we present a new technique to monitor dynamic conformational changes in
      voltage-sensitive membrane-bound proteins using radio frequency (RF) impedance
      measurements. Xenopus oocytes were transfected to express ShakerB-IR K(+) ion
      channels, and step changes in membrane potential were applied using two-electrode
      voltage clamp (TEVC). Simultaneously, bipolar extracellular electrodes were used
      to measure the RF electrical impedance across the cell (300 kHz - 1 MHz). RF
      current will either pass through the media, around the cell, or displace charge
      across the cell membrane. The change in displacement current in the cell membrane
      during voltage clamp resulted in measurable RF impedance change. RF impedance
      change during DC membrane depolarization was significantly greater in ShakerB-IR
      expressing oocytes than in endogenous controls at 300 kHz, 500 kHz and, to a
      lesser extent, 1 MHz. Since the RF were too high to modulate ShakerB-IR protein
      conformational state (e.g. open channel probability), impedance changes are
      interpreted as reflections of voltage-dependent protein conformation and
      associated biophysics such as ion-channel dipole interactions, fluctuations in
      bound water, or charged lipid head-group rotations.

PMID- 21097204
TI  - Microphone array based novel infant deafness detector.
AB  - This work focuses on an infant deafness detector unit, using the concept of
      microphone array. This instrument is based on the principle of evoked acoustic
      emissions (OAEs). The key feature of the microphone array is its ability to
      increase signal-to-noise ratio (SNR) and reproducibility of the OAE responses.
      These further significantly contribute to improve the sensitivity and specificity
      of the overall system. Low level sound pressure values are recorded by the
      sensitive microphones in microphone array unit and processed using TI's DSP6416.
      The sound stimulus transmitted to human ear is generated and controlled by the
      6416 DSP (Digital signal processor). Hardware circuit details and the algorithm
      used in signal processing are discussed in this paper. Standard averaging
      technique is used in the implemented algorithm. The final result speaks about the
      hearing capacity of a patient. The proof that the usage of microphone arrays
      leads to better SNR values than using a single microphone in an OAE probe, is
      successfully carried out in this work.

PMID- 21097205
TI  - Pilot study of longitudinal ultrasonic sensor for dynamic volumetric assessment
      of gastroesophageal reflux.
AB  - In patients with gastroesophageal reflux disease (GERD), esophageal symptoms are
      traditionally diagnosed by monitoring the contact time between the reflux content
      and the esophagus using multichannel intraluminal impedance and pH (MII-pH)
      catheters. However, esophageal catheter for quantifying the volume of reflux
      content is still lacking. The present work proposes an innovative method to
      develop a longitudinal ultrasonic catheter and an information extraction system
      for reflux event detection and reflux volume estimation. Gastroesophageal model
      that mimics reflux events was developed to test the proposed catheter. Ultrasonic
      sensing was evaluated by simulating different volumes of reflux. The obtained
      signals showed good consistency in detecting reflux events and measuring reflux
      volume. During an in vivo human testing, a MII-pH catheter was used
      simultaneously to compare the ultrasonic output. Both in vitro and in vivo human
      testing results demonstrated the feasibility of utilizing the proposed method for
      gastroesophageal reflux (GER) detection and reflux volume estimation.

PMID- 21097206
TI  - High-efficiency optical systems for interrogation of dermally-implanted sensors.
AB  - Ratiometric Luminescent microparticle sensors have been developed for sensing
      biochemical targets such as glucose in interstitial fluid, enabling use of dermal
      implants for on-demand monitoring. For these sensor systems to be deployed in
      vivo, a matched optoelectronic system for interrogation of dermally-implanted
      sensors was previously designed, constructed, and evaluated experimentally.
      During evaluation experiments, it revealed that the system efficiency was
      compromised by losses due to fiber connections, the entrance aperture, and the
      entrance slit of the spectrometer. In this work, two optimization methods were
      investigated to overcome photon loss at fiber connections and internal trade-off
      between resolution and input light power of the current spectrometer: 1)
      Replacement of the CCD spectrometer with a two-detector system, enabling
      extraction of key spectral information by integrating signals over two wavelength
      regions (reference and sensing emission peaks); and 2) Free-space coupling of the
      optical probe to a custom low-resolution spectrometer. Photon loss was evaluated
      by experiments and simulations, preliminary hardware of two-detector system was
      constructed, and optimization simulations were performed to explore conceptual
      feasibility of the free-space coupling custom-designed spectrometer.

PMID- 21097207
TI  - Mobile healthcare information management utilizing Cloud Computing and Android
      OS.
AB  - Cloud Computing provides functionality for managing information data in a
      distributed, ubiquitous and pervasive manner supporting several platforms,
      systems and applications. This work presents the implementation of a mobile
      system that enables electronic healthcare data storage, update and retrieval
      using Cloud Computing. The mobile application is developed using Google's Android
      operating system and provides management of patient health records and medical
      images (supporting DICOM format and JPEG2000 coding). The developed system has
      been evaluated using the Amazon's S3 cloud service. This article summarizes the
      implementation details and presents initial results of the system in practice.

PMID- 21097208
TI  - e_Disease Management. A system for the management of the chronic conditions.
AB  - Disease Management (DM) is a system of coordinated healthcare intervention and
      communications for populations with conditions in which patient self-care efforts
      are significant. e-DM makes reference to processes of DM based on clinical
      guidelines sustained in the scientific medical evidence and supported by the
      intervention of Information and Telecommunication Technology (ICT) in all levels
      where these plans are developed. This paper discusses the design and
      implementation of a e-DM system which meets the requirements for the integrated
      chronic disease management following the recommendations of the Disease
      Management Association and the American Heart Association.

PMID- 21097209
TI  - An overview of recent end-to-end wireless medical video telemedicine systems
      using 3G.
AB  - Advances in video compression, network technologies, and computer technologies
      have contributed to the rapid growth of mobile health (m-health) systems and
      services. Wide deployment of such systems and services is expected in the near
      future, and it's foreseen that they will soon be incorporated in daily clinical
      practice. This study focuses in describing the basic components of an end-to-end
      wireless medical video telemedicine system, providing a brief overview of the
      recent advances in the field, while it also highlights future trends in the
      design of telemedicine systems that are diagnostically driven.

PMID- 21097210
TI  - Integration of heterogeneous biomedical sensors into an ISO/IEEE 11073 compliant
      application.
AB  - Current trends in healthcare technology include mobile-based applications.
      Relevant advances in the integration of vital signs monitoring devices with
      mobile platforms are widely reported nowadays. In this context, conceiving and
      designing an interoperable application is essential due to the growing necessity
      of integrating a huge and heterogeneous amount of biomedical data, coming from a
      wide range of devices and sensors. In this paper the key research issues
      associated with such integration are presented as well as a specific proposal to
      solve these problems. It is based on a middleware architecture for the
      integration of biomedical sensors with mobile devices, derived from the ISO/IEEE
      11073 standards family. The application has been developed in the framework of an
      EU-funded R&D project called METABO.

PMID- 21097211
TI  - Personalized health applications in the Web 2.0: the emergence of a new approach.
AB  - Health consumers have embraced the web to obtain access to health information and
      to socialize and share knowledge with peers. Additionally, the web has become a
      more interactive and rich platform with the integration of health applications
      and services, such as Personal Health Records. Some of these applications provide
      personalized interactions based on user specific characteristics. In this paper
      we provide an overview of Personalized Health Applications in the Web 2.0. We
      reviewed the health applications integrated in Google Health, Microsoft
      HealthVault and Facebook. We studied the goals of the applications and also the
      personalized feedback they provided.

PMID- 21097212
TI  - A fast critical arrhythmic ECG waveform identification method using cross
      correlation and multiple template matching.
AB  - Critical Arrhythmic ECG such as Ventricular Tachycardia (VT) and Ventricular
      Fibrillation (VF) are both distinguishable by its waveform characteristics. A VF
      waveform is often described as disorganized and has an irregular rhythm while a
      VT waveform exhibits abnormal signatures and presents a regular rhythm pattern.
      This paper presents a fast cross-correlation algorithm using multiple waveform
      templates for automatic detection of life threatening arrhythmias such as VT and
      VF from the Normal Sinus Rhythm (NSR) waveforms. A sliding-window template cross
      correlation technique is applied to an ECG signal to generate an array of
      correlation coefficients. Then a correlation coefficient curve is used to detect
      high coefficient values for a type of template that will quantify the similarity
      between an examined ECG signal and a template. The method presented in this paper
      is able to detect all three different types of ECG signals from a total 21
      testing signal set with a satisfied correct rate.

PMID- 21097213
TI  - Applying machine learning to detect individual heart beats in
      ballistocardiograms.
AB  - Ballistocardiography is a technique in which the mechanical activity of the heart
      is recorded. We present a novel algorithm for the detection of individual heart
      beats in ballistocardiograms (BCGs). In a training step, unsupervised learning
      techniques are used to identify the shape of a single heart beat in the BCG. The
      learned parameters are combined with so-called "heart valve components" to detect
      the occurrence of individual heart beats in the signal. A refinement step
      improves the accuracy of the estimated beat-to-beat interval lengths. Compared to
      other algorithms this new approach offers heart rate estimates on a beat-to-beat
      basis and is designed to cope with arrhythmias. The proposed algorithm has been
      evaluated in laboratory and home settings for its agreement with an ECG
      reference. A beat-to-beat interval error of 14.16 ms with a coverage of 96.87%
      was achieved. Averaged over 10 s long epochs, the mean heart rate error was 0.39
      bpm.

PMID- 21097214
TI  - Classification of low systemic vascular resistance using photoplethysmogram and
      routine cardiovascular measurements.
AB  - Low systemic vascular resistance (SVR) can be a useful indicator for early
      diagnosis of critical pathophysiological conditions such as sepsis, and the
      ability to identify low SVR from simple and noninvasive physiological signals is
      of immense clinical value. In this study, an SVR classification system is
      presented to recognize the occurrence of low SVR, among a heterogenous group of
      patients (N = 48), based on the use of routine cardiovascular measurements and
      features extracted from the finger photoplethysmogram (PPG) as inputs to a
      quadratic discriminant classifier. An exhaustive feature search was performed to
      identify a near optimum feature subset. Cohen's kappa coefficient (kappa) was
      used as a performance measure to compare candidate feature sets. The classifier
      using the following combination of features performed best (kappa = 0.56,
      sensitivity = 96.30%, positive predictivity = 92.31%): normalized low-frequency
      power (LFNU) derived from PPG, ratio of low-frequency power to high-frequency
      power (LF/HF) of the PPG variability signal, and the ratio of mean arterial
      pressure to heart rate (MAP/HR). Classifiers that used either LF(NU) (kappa =
      0.43), LF/HF (kappa = 0.37) or MAP/HR (kappa = 0.43) alone showed inferior
      performance. Discrimination of patients with and without low SVR can be achieved
      with reasonable accuracy using multiple features derived from the PPG combined
      with routine cardiovascular measurements.

PMID- 21097215
TI  - Wavelet-based markers of ventricular fibrillation in optimizing human cardiac
      resuscitation.
AB  - During cardiac resuscitation from ventricular fibrillation (VF) it would be
      helpful if we could monitor and predict the optimal state of the heart to be
      shocked into a perfusing rhythm. Real-time feedback of this state to the
      emergency medical staff (EMS) could improve the survival rate after
      resuscitation. In this paper, using real world out-of-the-hospital human VF data
      obtained during resuscitation by EMS personnel, we present the results of
      applying wavelet markers in predicting the shock outcomes. We also performed
      comparative analysis of 5 existing techniques (spectral and correlation based
      approaches) against the proposed wavelet markers. A database of 29 human VF
      tracings was extracted from the defibrillator recordings collected by the EMS
      personnel and was used to validate the waveform markers. The results obtained by
      the comparison of the wavelet based features with other spectral, and correlation
      based features indicates that the proposed wavelet features perform well with an
      overall accuracy of 79.3% in predicting the shock outcomes and hence demonstrate
      potential to provide near real-time feedback to EMS personnel in optimizing
      resuscitation outcomes.

PMID- 21097216
TI  - Influences of sites and protocols on inducing ventricular fibrillation: A
      computer simulation study.
AB  - In cardiac electrophysiological study, several electrical stimulation protocols
      have been employed to induce ventricular fibrillations (VF). In addition, sites
      of inducing may have different impacts on inducing results as well as different
      inducing protocols. To study whether VF inducing method is determinant of induced
      outcome, we simulated VFs induced with different protocols at different sites
      based on the Wei-Harumi whole heart model. Simulations showed that only certain
      combinations of pacing protocols and sites could induce sustainable VFs, which
      had similar frequency distributions. This result suggested that the interactions
      between protocols and sites determine the odds of successful inducing but once
      the VF was induced, the pattern was solely determined by inner cardiac
      properties.

PMID- 21097217
TI  - Prediction of ventricular fibrillation based on the ST-segment deviation:
      allometric model.
AB  - Based on some reported clinical data, we attempt to apply the allometric law for
      evaluating the probability of ventricular fibrillation when electrocardiographic
      ST-segment deviations are determined. The deviation is measured in millimeters at
      the standard calibration of 1mV = 10mm and the probability in percent. Using the
      equation VF(P) = delta + beta (ST) in log-log representation, the fitting
      procedure produced the following overall coefficients: Average beta = 1.11, with
      a maximum = 1.65 and a minimum = 0.78; Average delta = 0.83, with a maximum =
      1.39 and a minimum = 0.41. For a 2mm ST-deviation, the full range of predicted
      ventricular fibrillation probability extended from about 6% at 1 month up to 47%
      at 4 years after the original cardiac event. These results, at least
      preliminarily, appear acceptable and still call for full clinical test. The model
      seems promising if other parameters were taken into account, such as cardiac
      enzyme concentration, ischemic or infarcted epicardial areas or ejection
      fraction. It is concluded, considering these results and a few references found
      in the literature, that the allometric model shows promising features in
      cardiology.

PMID- 21097218
TI  - Distinguishing between ventricular tachycardia and ventricular fibrillation from
      compressed ECG signal in wireless Body Sensor Networks.
AB  - Since ECG is huge in size sending large volume data over resource constrained
      wireless networks is power consuming and will reduce the energy of nodes in Body
      Sensor Networks (BSN). Therefore, compression of ECGs and diagnosis of diseases
      from compressed ECGs will play key roles in enhancing the life-time of body
      sensor networks. Moreover, discrimination between ventricular Tachycardia and
      Ventricular Fibrillation is of crucial importance to save human life. Existing
      algorithms work only on plain text ECGs to distinguish between the two, and
      therefore, not suitable in BSN. VT and VF are often similar in patterns and in
      filtration of noise and improper attribute selection in compressed ECGs will make
      it even harder to classify them properly. In this paper, a supervised attribute
      selection algorithm called Correlation Based Feature Selection (CFS) [4] is used
      to filter the unwanted attributes and select the most relevant attributes. We
      then use the selected attributes to train and classify VT and VF using Radial
      Basis Function (RBF) Neural Network and k-nearest neighbour techniques. We
      experimented with 103 ECG samples taken from MIT-BIH Malignant Ventricular Ectopy
      Database. Results showed that accuracy can be as high as 93.3% when attribute
      selection is used and large number of training samples are provided.

PMID- 21097219
TI  - Power optimization in body sensor networks: the case of an autonomous wireless
      EMG sensor powered by PV-cells.
AB  - Recent advances in ultra-low-power circuits and energy harvesters are making self
      powered body sensor nodes a reality. Power optimization at the system and
      application level is crucial in achieving ultra-low-power consumption for the
      entire system. This paper reviews system-level power optimization techniques, and
      illustrates their impact on the case of autonomous wireless EMG monitoring. The
      resulting prototype, an Autonomous wireless EMG sensor power by PV-cells, is
      presented.

PMID- 21097220
TI  - Advances in wearable technology and its medical applications.
AB  - The concept of monitoring individuals in the home and community settings was
      introduced more than 50 years ago, when Holter monitoring was proposed (in the
      late 1940s) and later adopted (in the 1960s) as a clinical tool. However,
      technologies to fully enable such vision were lacking and only sporadic and
      rather obtrusive monitoring techniques were available for several decades. Over
      the past decade, we have witnessed a great deal of progress in the field of
      wearable sensors and systems. Advances in this field have finally provided the
      tools to implement and deploy technology with the capabilities required by
      researchers in the field of patients' home monitoring. These technologies provide
      the tools to achieve early diagnosis of diseases such as congestive heart
      failure, prevention of chronic conditions such as diabetes, improved clinical
      management of neurodegenerative conditions such as Parkinson's disease, and the
      ability to promptly respond to emergency situations such as seizures in patients
      with epilepsy and cardiac arrest in subjects undergoing cardiovascular
      monitoring. Current research efforts are focused on the development of systems
      enabling clinical applications. The current focus on developing and deploying
      wearable systems targeting specific clinical applications has the potential of
      leading to clinical adoption within the next five to ten years.

PMID- 21097221
TI  - Estimation of rest-activity patterns using motion sensors.
AB  - Disrupted sleep patterns are a significant problem in the elderly, leading to
      increased cognitive dysfunction and risk of nursing home placement. A cost
      effective and unobtrusive way to remotely monitor changing sleep patterns over
      time would enable improved management of this important health problem. We have
      developed an algorithm to derive sleep parameters such as bed time, rise time,
      sleep latency, and nap time from passive infrared sensors distributed around the
      home. We evaluated this algorithm using 404 days of data collected in the homes
      of 8 elderly community-dwelling elders. Data from this algorithm were highly
      correlated to ground truth measures (bed mats) and were surprisingly robust to
      variability in sensor layout and sleep habits.

PMID- 21097222
TI  - Model based control of a rehabilitation robot for lower extremities.
AB  - This paper mainly focuses on the trajectory tracking control of a lower extremity
      rehabilitation robot during passive training process of patients. Firstly, a
      mathematical model of the rehabilitation robot is introduced by using Lagrangian
      analysis. Then, a model based computed-torque control scheme is designed to
      control the constrained four-link robot (with patient's foot fixed on robot's end
      effector) to track a predefined trajectory. Simulation results are provided to
      illustrate the effectiveness of the proposed model based computed-torque
      algorithm. In the simulation, a multi-body dynamics and motion software named
      ADAMS is used. The combined simulation of ADAMS and MATLAB is able to produce
      more realistic results of this complex integrated system.

PMID- 21097223
TI  - Evaluation of leg joint trajectories while carrying out passive manipulation by
      NEUROBike.
AB  - During the last decades, many robotic platforms aimed at post-stroke
      neurorehabilitation of locomotion have been developed. These devices have been
      designed to enhance the possibilities of conventional rehabilitation providing
      safe, highly accurate, intensive and prolonged treatments. Nevertheless, up to
      now, robotic aided therapy has not yet promoted improvements of the motor
      performance significantly greater than those achieved by the conventional
      therapy. According to previous studies, we believe that this result may be
      partially ascribed to two main issues: the rehabilitation mediated by robots is
      usually provided too late from the trauma and it mainly consists of passive and
      cyclic manipulation of the legs. Our proposal to overcome some of the supposed
      limits is NEUROBike, an operative mechatronic platform able to lead leg
      manipulation as soon as possible after the trauma, that is when patients still
      lie on their own beds. Moreover, NEUROBike has been designed to provide both
      passive and cyclic manipulation of leg joints with trajectories similar to those
      related to natural walking, and motor task involving random efforts. This work
      presents the comparison between desired and measured leg joint trajectories while
      NEUROBike provides cyclic and passive leg manipulation. The results show that
      angular excursions at proximal joints were reasonably comparable with those
      obtained by the velocity based model even though they were affected by a positive
      offset involving emphasized flexion of hip and knee during the gait cycle.

PMID- 21097224
TI  - Benzodiazepine administration effect on EEG fractal dimension: results and
      causalities.
AB  - This work aims at examining the influence of lorazepam, an anxiolytic drug with
      sedative effects, on brain activity and specifically on EEG Fractal Dimension
      (FD). The main objective is to clarify the reasons for FD increase after drug
      intake and to establish a relationship between FD and EEG energy bands. 14
      healthy subjects that received either 2.5mg of lorazepam (verum case) or placebo
      (placebo case) participated in the experiment. 20 EEG channels have been used.
      One-way ANOVA test revealed that lorazepam increases significantly both FD (p =
      0) and beta energy band (p = 1.18E-013 for beta1 band and p = 2.29E-011 for beta2
      band) and decreases alpha energy band (p = 0.05 for alpha1 and p = 0.0036 for
      alpha2), whereas there was not any significant difference on placebo subjects
      before and after drug intake. Moreover, correlation results indicate that there
      is a strong correlation between FD and beta energy band (mean correlation
      coefficient = 0.4120 for beta1 and 0.5358 for beta2) and a negative correlation
      between FD and alpha1 energy band (mean correlation coefficient -0.4930).
      Additionally, the mean correlation coefficient between FD and a combination of
      the different energy bands (beta1+beta2-alpha1) is 0.6185 and reaches value 0.684
      for channels F7, T6, P4. These results indicate that there is a relationship
      between EEG energy bands and FD and provide a link between the classic spectral
      analysis and the complexity analysis.

PMID- 21097225
TI  - Implementation of a real-time algorithm for maternal and fetal heart rate
      monitoring in a digital signal controller platform.
AB  - An LMS-based algorithm to monitor fetal and maternal heart rate in real time was
      implemented and evaluated on a development platform. Hardware has three modules:
      dsPIC30F digital signal controller, a low-noise analog front end and a storage
      stage. They were evaluated using on-chip debugging tools and a patient simulator.
      Algorithm performance was tested using simulation tools and real data. Other
      measures like process run-times and power consumption, were analyzed to evaluate
      the design feasibility. Dataset was conformed by 25 annotated records from
      different gestational age pregnant women. Sensitivity and accuracy were used as
      performance measures. In general, sensitivity was high for maternal (95.3%) and
      fetal (87.1%) detections. Results showed that the chosen architecture can run
      efficiently the algorithm processes, obtaining high detection rates under
      appropriate SNR conditions.

PMID- 21097226
TI  - Development of a multimodal monitoring platform for medical research.
AB  - A low cost multimodal monitoring and signal processing platform is presented. A
      modular and flexible system was developed, aimed to continuous acquisition of
      several biological variables at patient bed-head and further processing with
      application specific algorithms. System hardware is made of a six-channel
      isolation and signal conditioning front-end along with a high resolution analog
      to-digital converter board connected to a standard laptop. Whole system hardware
      is compact and light weight, which ensures portability and ease of use at
      intensive care units. System software is divided in three modules: Acquisition,
      Signal Processing and Patients Data Management. The first one allows configuring
      each acquisition channel parameters, depending on the biological variable
      connected to it, and to store up to several hours of continuous data. Signal
      processing module implements novel algorithms for research purposes like dynamic
      cerebral autoregulation, optimal perfusion pressure, critical closing pressure or
      pulsatility index. It is flexible enough to easily add new processing algorithms,
      export data to different formats and create graphical reports. Patients data
      management module organizes acquired records, which allows selecting cases for
      new studies based on different criteria like monitored variables or pathological
      information. In this work, whole system architecture is described and algorithms
      included into the cerebral hemodynamics toolbox are presented along with
      experimental results.

PMID- 21097227
TI  - Estimation of ankle joint angle from peroneal and tibial electroneurograms based
      on muscle spindle model.
AB  - The main goal of this study was to develop a new method of estimating the angle
      of the passively stretched ankle joint, based on structural muscle spindle models
      of the tibial and peroneal electroneurograms (ENG). Passive ramp-and-hold and
      alternating stretches of the ankle joint were performed in a rabbit.
      Simultaneously, two cuff electrodes were used to record the ENGs of peroneal and
      tibial nerves. Based on the two ENGs and the joint angle trajectory, two muscle
      spindle models were constructed and their inverse models were integrated to
      compute angle estimates. The model parameters were optimized. The performance of
      our approach was compared with those of the adaptive neuro-fuzzy inference system
      and artificial neural network model. The results revealed that our model had a
      better performance of estimating the ankle joint angle in large-range movements
      and smaller tracking errors. This study provides a new estimation algorithm to
      extract the joint angle from the information conveyed in a nerve.

PMID- 21097228
TI  - Influence of rotary blood pumps over preload recruitable stroke work.
AB  - When recovery of the cardiac function is detected in assisted hearts, the
      ventricular assist device can be removed. Due to the invasiveness of the surgical
      procedure, an accurate assessment of cardiac function is fundamental for the
      treatment success. The main challenge for the detection of cardiac function
      during assistance is to know whether the cardiac function index represents the
      cardiac function after pump removal independently of the pump assist rate.
      Therefore in this paper we present an evaluation of the influence of the pump
      over the slope of the preload recruitable stroke work, a cardiac function index.
      Analyzing data from four acute animal experiments, we found that the pump affects
      the stroke work, which could be corrected by the end diastolic volume. However,
      the data set examined was limited and further investigation is necessary.

PMID- 21097229
TI  - Incremental SSVEP analysis for BCI implementation.
AB  - This work presents an incremental analysis of EEG records containing Steady-State
      Visual Evoked Potential (SSVEP). This analysis consists of two steps: feature
      extraction, performed using a statistic test, and classification, performed by a
      decision tree. The result is a system with high classification rate (a test with
      six volunteers resulted in an average classification rate of 91.2%), high
      Information Transfer Rate (ITR) (a test with the same six volunteers resulted in
      an average value of 100.2 bits/min) and processing time, for each incremental
      analysis, of approximately 120 ms. These are very good features for an efficient
      Brain-Computer Interface (BCI) implementation.

PMID- 21097230
TI  - Multimodal BCI-mediated FES suppression of pathological tremor.
AB  - Tremor constitutes the most common movement disorder; in fact 14.5% of population
      between 50 to 89 years old suffers from it. Moreover, 65% of patients with upper
      limb tremor report disability when performing their activities of daily living
      (ADL). Unfortunately, 25% of patients do not respond to drugs or neurosurgery. In
      this regard, TREMOR project proposes functional compensation of upper limb
      tremors with a soft wearable robot that applies biomechanical loads through
      functional electrical stimulation (FES) of muscles. This wearable robot is driven
      by a Brain Neural Computer Interface (BNCI). This paper presents a multimodal BCI
      to assess generation, transmission and execution of both volitional and tremorous
      movements based on electroencephalography (EEG), electromyography (EMG) and
      inertial sensors (IMUs). These signals are combined to obtain: 1) the intention
      to perform a voluntary movement from cortical activity (EEG), 2) tremor onset,
      and an estimation of tremor frequency from muscle activation (EMG), and 3)
      instantaneous tremor amplitude and frequency from kinematic measurements (IMUs).
      Integration of this information will provide control signals to drive the FES
      based wearable robot.

PMID- 21097231
TI  - Online performance evaluation of motor imagery BCI with augmented-reality virtual
      hand feedback.
AB  - The online performance of a motor imagery-based Brain-Computer Interface (MI-BCI)
      influences its effectiveness and usability in real-world clinical applications
      such as the restoration of motor control. The online performance depends on
      factors such as the different feedback techniques and motivation of the subject.
      This paper investigates the online performance of the MI-BCI with an augmented
      reality (AR) 3D virtual hand feedback. The subject experiences the interaction
      with 3D virtual hands, which have been superimposed onto his real hands and
      displayed on the computer monitor from a first person point-of-view. While
      performing motor imagery, he receives continuous visual feedback from the MI-BCI
      in the form of different degrees of reaching and grasping actions of the 3D
      virtual hands with other virtual objects. The AR feedback is compared with the
      conventional horizontal bar feedback on 8 subjects, of whom 7 are BCI-naive. The
      subjects found the AR feedback to be more engaging and motivating. Despite the
      higher mental workload involved in the AR feedback, their online MI-BCI
      performance compared to the conventional horizontal bar feedback was not
      affected. The results provide motivation to further develop and refine the AR
      feedback protocol for MI-BCI.

PMID- 21097232
TI  - Motor imagery task discrimination using wide-band frequency spectra with Slepian
      tapers.
AB  - We here studied the efficacy of wide-band frequency spectra (WBFS) features using
      multi-taper (MT) spectral analysis in application to motor imagery based Brain
      Computer Interfaces. We acquired motor imagery task related human scalp
      electroencephalography (EEG) signals for left vs. right hand movements using 3
      different pairs of visual arrow cues. Left vs. right movement imagery
      discrimination was conducted using a Naive Bayesian classifier using WBFS
      features and commonly used Mu-Beta spectral features for EEG signals from
      central+parietal and central only electrode positions. Task discrimination
      accuracy results showed that WBFS features using MT spectral analysis provided
      significantly better performance (with a 95% confidence level) than that of using
      Mu-Beta spectral features commonly used. The use of central+parietal electrode
      signals improved discrimination accuracy significantly when compared to the
      accuracy using the central only signals, implying that sensory information
      enhanced task discrimination significantly.

PMID- 21097233
TI  - Characterization of gait abnormalities in Parkinson's disease using a wireless
      inertial sensor system.
AB  - Gait analysis is important in diagnosing and evaluating certain neurological
      diseases such as Parkinson's disease (PD). In this paper, we show the ability of
      our wireless inertial sensor system to characterize gait abnormalities in PD. We
      obtain physical features of pitch, roll, and yaw rotations of the foot during
      walking, use principal component analysis (PCA) to select features, and use the
      support vector machine (SVM) method to create a classification model. In the
      binary classification task of detecting the presence of PD by distinguishing
      between PD and control subjects, the model performs with over 93% sensitivity and
      specificity, and 97.7% precision. Using a cost-sensitive learner to reflect the
      different costs associated with misclassifying PD and control subjects,
      performance of 100% specificity and precision is achieved, while maintaining
      sensitivity of close to 89%. In the multi-class classification task of
      characterizing parkinsonian gait by distinguishing among PD with significant gait
      disturbance, PD with no significant gait disturbance, and control subjects, 91.7%
      class recall for control subjects is achieved and the model performs with 84.6%
      precision for PD subjects with significant gait disturbance. The features
      selected for this classification task indicate the features of gait that are
      principal in discriminating gait abnormalities due to PD compared to a normal
      gait. These results demonstrate the ability of our wireless inertial sensor
      system to successfully detect the presence of PD based on physical features of
      gait and to identify the specific features that characterize parkinsonian gait.

PMID- 21097234
TI  - Using rapid prototyping molds to create patient specific polymethylmethacrylate
      implants in cranioplasty.
AB  - Cranioplasty is a commonly performed procedure. Outcomes can be improved by the
      use of patient specific implants, however, high costs limit their accessibility.
      This paper presents a low cost alternative technique to create patient specific
      polymethylmethacrylate (PMMA) implants using rapid prototyped mold template. We
      used available patient's CT-scans, one dataset without craniotomy and one with
      craniotomy, for computer-assisted design of a 3D mold template, which itself can
      be brought into the operating room and be used for fast and easy building of a
      PMMA implant. We applied our solution to three patients with positive outcomes
      and no complications.

PMID- 21097235
TI  - Inductive tongue control of powered wheelchairs.
AB  - Alternative and effective methods for controlling powered wheelchairs are
      important to individuals with tetraplegia and similar impairments whom are unable
      to use the standard joystick. This paper describes a system where tongue
      movements are used to control a powered wheelchair thus providing users, with
      high level spinal cord injuries, full control of their wheelchair. The system is
      based on an inductive tongue control system developed at Center for Sensory-Motor
      Interaction (SMI), Aalborg University. The system emulates a standard analog
      joystick in order to interface the wheelchair, thus ensuring that the system
      works with almost any wheelchair. The total embedment of the tongue interface
      into the mouth makes the control practically invisible. A fuzzy system combining
      8 sensors for directional control allows for multidirectional control of the
      wheelchair. Preliminary test results show navigation abilities, which are highly
      competitive when compared to other tongue control system.

PMID- 21097236
TI  - Clinical evaluation of wireless inductive tongue computer interface for control
      of computers and assistive devices.
AB  - Typing performance of a full alphabet keyboard and a joystick type of mouse (with
      on-screen keyboard) provided by a wireless integrated tongue control system (TCS)
      has been investigated. The speed and accuracy have been measured in a form of a
      throughput defining the true correct words per minute [cwpm]. Training character
      sequences were typed in a dedicated interface that provided visual feedback of
      activated sensors, a map of the alphabet associated, and the task character.
      Testing sentences were typed in Word, with limited visual feedback, using non
      predictive typing (map of characters in alphabetic order associated to sensors)
      and predictive typing (LetterWise) for TCS keyboard, and non-predictive typing
      for TCS mouse. Two subjects participated for four and three consecutive days,
      respectively, two sessions per day. Maximal throughput of 2.94, 2.46, and 2.06,
      1.68 [cwpm] were obtained with TCS keyboard by subject 1 and 2 with predictive
      and non-predictive typing respectively. Maximal throughput of 2.09 and 1.71
      [cwpm] was obtained with TCS mouse by subject 1 and 2, respectively. Same
      experimental protocol has been planned for a larger number of subjects.

PMID- 21097237
TI  - Evaluation of a mobile electrode for electrical stimulation of the perineal
      muscle.
AB  - This work evaluates the effectiveness of a new type of electrode for functional
      electrical stimulation of the perineal muscle in women. The new electrode is
      shaped like a pen, with an active stimulation electrode located on its tip. The
      goals of the study are to (i) demonstrate that stimulation using the new device
      results in increased muscle strength; and (ii) compare the performance of the new
      device with that of a traditional (fixed) electrode. Eight women were evaluated,
      following a blind study protocol. The preliminary results suggest that
      stimulation with the new electrode achieves better results than stimulation with
      traditional electrodes, as higher increases in strength were observed in the
      group that used the mobile electrode.

PMID- 21097238
TI  - Evaluation method for the proficiency level of an operating myoelectric hand
      using EMG signals.
AB  - To evaluate the proficiency level of an operating myoelectric hand, we proposed
      an evaluation index consisting of the accuracy and the reproducibility of
      electromyography (EMG) signal patterns. Our proposed method is not an absolute
      evaluation because we use bio-signals, so it is necessary to verify the
      correlation between the proposed index and performance evaluation to confirm the
      usefulness of the index. Therefore, we conducted classification tests on eight
      forearm motions and verified the correlation between the proposed method and the
      classification rate. There was a strong correlation between the accuracy and the
      classification rate. In addition, if the accuracy was high, high reproducibility
      led to an increase in the classification rate. We conclude that the proposed
      method can evaluate the proficiency level of a myoelectric hand.

PMID- 21097239
TI  - Optical tools to produce and study small strokes in animal models.
AB  - Clinical evidence shows that ischemic and hemorrhagic microvascular lesions in
      the brain play an important role in elderly dementia [1-4], but few effective
      treatment or preventative strategies exist. This deficit is due, in part, to a
      lack of good animal models of these microvascular lesions that would allow the
      progression of disease to be studied and would provide a platform for the
      evaluation of therapeutics. Here, we discuss recent advances in optical
      techniques that allow both the targeted production of single-vessel occlusions
      and hemorrhages in the cortex of anesthetized rodents, as well as the
      quantitative analysis of the impact of these lesions on blood flow in the
      adjacent vascular network and on the health and function of nearby brain cells.
      These new optical tools offer a comprehensive animal model of small-scale stroke
      that will enable the progression of neural damage after a microvascular insult as
      well as the interaction of small strokes with other neurodegenerative conditions,
      such as Alzheimer's disease, to be studied.

PMID- 21097240
TI  - Imaging optically induced neural activity in the brain.
AB  - Infrared neural stimulation (INS) is well characterized for the peripheral
      nervous system; however, translation to the central nervous system (CNS) presents
      a new set of challenges which require us to consider different anatomy, multiple
      cell types, and the physiology associated with structures in the CNS. This study
      presents our first attempt to translate INS to in vivo stimulation of the CNS and
      to image the related response. The results from this study show that INS
      generates intrinsic optical signals of similar magnitude and shape associated
      with well characterized mechanical stimuli. The implications of this work could
      lead to neural implants which allows for single cell stimulation making it
      possible to design closed loop neural prosthetics.

PMID- 21097241
TI  - Label-free high-resolution imaging of live cells with deconvolved spatial light
      interference microscopy.
AB  - Spatial light interference microscopy (SLIM) is a powerful new quantitative phase
      optical imaging technique that can be used for studying live cells without the
      need for exogenous contrast agents. This paper proposes a novel deconvolution
      based approach to reconstructing SLIM data, which dramatically improves the
      visual quality of the images. The proposed deconvolution formulation is tailored
      to the physics of SLIM imaging of biological samples, and a new fast algorithm is
      designed for computationally-efficient image reconstruction in this setting.
      Simulation and experimental results demonstrate that deconvolution can reduce the
      width of the point-spread function by at least 20%, and can significantly improve
      the contrast of high-resolution features. Temporally-resolved SLIM imaging with
      the high spatial resolution enabled by deconvolution provides new opportunities
      for studying the dynamics of cellular and sub-cellular processes.

PMID- 21097242
TI  - 3-D flow characterization and shear stress in a stenosed carotid artery
      bifurcation model using stereoscopic PIV technique.
AB  - The carotid artery bifurcation is a common site of atherosclerosis which is a
      major leading cause of ischemic stroke. The impact of stenosis in the
      atherosclerotic carotid artery is to disturb the flow pattern and produce regions
      with high shear rate, turbulence, and recirculation, which are key hemodynamic
      factors associated with plaque rupture, clot formation, and embolism. In order to
      characterize the disturbed flow in the stenosed carotid artery, stereoscopic PIV
      measurements were performed in a transparent model with 50% stenosis under
      pulsatile flow conditions. Simulated ECG gating of the flowrate waveform provides
      external triggering required for volumetric reconstruction of the complex flow
      patterns. Based on the three-component velocity data in the lumen region,
      volumetric shear-stress patterns were derived.

PMID- 21097243
TI  - PSF model-based reconstruction with sparsity constraint: algorithm and
      application to real-time cardiac MRI.
AB  - The partially separable function (PSF) model has been successfully used to
      reconstruct cardiac MR images with high spatiotemporal resolution from sparsely
      sampled (k,t)-space data. However, the underlying model fitting problem is often
      ill-conditioned due to temporal undersampling, and image artifacts can result if
      reconstruction is based solely on the data consistency constraints. This paper
      proposes a new method to regularize the inverse problem using sparsity
      constraints. The method enables both partial separability (or low-rankness) and
      sparsity constraints to be used simultaneously for high-quality image
      reconstruction from undersampled (k,t)-space data. The proposed method is
      described and reconstruction results with cardiac imaging data are presented to
      illustrate its performance.

PMID- 21097244
TI  - Denoising in fluorescence microscopy using compressed sensing with multiple
      reconstructions and non-local merging.
AB  - The cross-dependency of noise level and photobleaching in microscopy was
      discussed in a previous work and an efficient compressed sensing (CS) method was
      proposed to simultaneously reduce the noise level and the photobleaching. Here we
      present an improved CS denoising framework for fluorescence microscopy images,
      exploiting Non-Local means filtering to merge multiple reconstructions. This
      framework enables high-quality reconstruction of low exposed microscopy images
      based on random Fourier sampling schemes and multiple CS reconstructions.
      Practical experiments on fluorescence images demonstrate that even performing 10%
      of the measurements, the signal-to-noise ratio can be significantly improved
      while keeping reduced exposure time, preserving edges and the image sharpness.

PMID- 21097245
TI  - Microwave tomography in the context of complex breast cancer imaging.
AB  - The notion of applying microwave imaging to breast cancer imaging has been
      studied at various levels by numerous scientists. The earliest appeal of this
      concept related to the presumably high property contrast between benign and
      malignant tissue that was unique to the breast. Subsequent published studies have
      shown that this assumption was overly simplistic and that the tissue property
      heterogeneity is considerable within the breast. As we have expanded the clinical
      use of our microwave tomographic system, we are now using this approach to
      monitor tumor progressions during neoadjuvant chemotherapy. In these cases, while
      we can still characterize and track the tumor progression, we have observed a new
      phenomenon. Very often these cancer patients exhibit skin thickening near the
      tumor site. Our images have reconstructed elevated dielectric properties along
      the breast surface associated with the accompanying edema. These observations
      further add to the complex nature of breast dielectric properties and the
      challenges for imaging them using microwave interrogation.

PMID- 21097246
TI  - Avoiding local optima of the joint entropy prior in limited view tomography using
      a multiresolution scheme.
AB  - The incorporation of anatomical reference images into limited view transmission
      tomography has been attempted previously by using the joint entropy prior.
      However, this prior has been found to be sensitive to local optima. Here, we
      propose to increase robustness to local optima by using a multiresolution
      optimisation scheme. To our knowledge, this is the first work to apply
      multiresolution optimisation to the joint entropy prior in limited view
      transmission tomography. The results show a substantial mitigation of the
      sensitivity to local optima, as well as a robustness to missing as well as extra
      regions in the anatomical reference image. In addition, we demonstrate the
      method's robustness to misalignment between the reconstruction and the anatomical
      reference image.

PMID- 21097247
TI  - An intention driven hand functions task training robotic system.
AB  - A novel design of a hand functions task training robotic system was developed for
      the stroke rehabilitation. It detects the intention of hand opening or hand
      closing from the stroke person using the electromyography (EMG) signals measured
      from the hemiplegic side. This training system consists of an embedded controller
      and a robotic hand module. Each hand robot has 5 individual finger assemblies
      capable to drive 2 degrees of freedom (DOFs) of each finger at the same time.
      Powered by the linear actuator, the finger assembly achieves 55 degree range of
      motion (ROM) at the metacarpophalangeal (MCP) joint and 65 degree range of motion
      (ROM) at the proximal interphalangeal (PIP) joint. Each finger assembly can also
      be adjusted to fit for different finger length. With this task training system,
      stroke subject can open and close their impaired hand using their own intention
      to carry out some of the daily living tasks.

PMID- 21097248
TI  - Abnormal adaptation in children affected by cerebral palsy to robot generated
      dynamic environment.
AB  - This paper aims to investigate how robotic devices can be used to understand the
      mechanism of sensorimotor adaptation in pediatric subjects affected by
      hemiparetic cerebral palsy. Previous studies showed how healthy adults, after
      training in presence of a systematic structured disturbing force field, show an
      "after effect" and therefore they highly adapt and compensate the external
      disturbance. An open issue is whether this adaptive capability is preserved or
      disrupted in pediatric impaired subjects when they experience a robot generated
      dynamic environment. Fourteen pediatric Cerebral Palsy subjects (CP group), and
      age-matched control group were exposed to a robot generated speed-dependant force
      field; during familiarization (no forces generated by the robot) the movement of
      the CP subjects were more curved, displaying greater and variable directional
      error; in the force field phase both the groups showed an after-effect, but the
      CP group had a non significant adaptation rate. This outcome suggests the CP
      subjects have reduced ability to learn external force and they make greater
      aiming error because of an inefficient anticipatory strategy during visuomotor
      task.

PMID- 21097249
TI  - Design and development of "biomechatronic gym" for early detection of
      neurological disorders in infants.
AB  - The study and measurement of grasping actions and forces in humans is important
      in a variety of contexts. In infants, it can give insights on the typical and
      atypical motor development, while it poses functional and operative requirements
      that are not fully matched by current sensing technology. Novel approaches for
      measuring infants' grasping actions are based on sensorized platform usable in
      natural settings. A new set of instrumented toys has been designed for the
      assessment/stimulation of upper limbs of infants between 4 and 9 months. A
      purposive biomechatronic gym has been developed by integrating pressure and force
      sensors and visual/auditory stimulations to the usual gym structure and hanging
      toys (cow, flower and ring puppets), so that the infants' actions on the gym can
      be monitored, measured and stimulated. With the developed system, a longitudinal
      clinical validation has been carried out with seven healthy infants. From data
      analysis it is possible to identify a trend in manual forces development and this
      result confirms the usefulness of the system proposed as a clinical tool for
      monitoring infants' grasping development.

PMID- 21097250
TI  - Are cutaneous reflexes from the foot preserved in passive walking in a DGO?
AB  - Driven Gait Orthosis (DGO) are commonly used in gait rehabilitation. These
      devices commonly lack an actuator at the ankle. As a result the ankle
      trajectories often differ considerably from those seen normally. The question
      arises whether these abnormal trajectories affect the phase-dependent modulation
      of cutaneous reflexes from the foot. To investigate this, the sural nerve was
      stimulated electrically at the end of the swing phase in subjects walking
      "passively" in a DGO. It was found that the tibialis anterior was less active at
      end swing during this type of walking and that the reflex induced suppression was
      absent. It is concluded that the normally occurring suppression does not depend
      on interactions from other sensory sources (since these are still present in
      "passive" walking). Instead the suppression is likely to depend on cortical
      activations. Training of these cortical activations may be reduced in current DGO
      walking and therefore it is argued that normalization of the ankle trajectory in
      future designs of DGO's could have a beneficial effect.

PMID- 21097251
TI  - Feasibility of dynamic entrainment with ankle mechanical perturbation to treat
      locomotor deficit.
AB  - Dynamically entraining human gait with periodic torque from a robot may provide
      an approach to walking therapy that is uniquely supportive of normal biological
      function. To test the feasibility of this approach we perturbed the gait of
      unimpaired human subjects by applying a periodic impulsive ankle torque at
      various frequencies. Eighteen subjects out of 19 exhibited entrained gaits: for a
      small range of frequencies their gait periods adapted to synchronize with the
      mechanical perturbation. In addition, the phase when synchronized was such that
      the robot perturbation assisted propulsion. These results support a new strategy
      for walking therapy that exploits an embedded neural oscillator interacting with
      peripheral mechanics and the resulting natural dynamics of walking, which are
      essential but hitherto neglected elements of walking therapy.

PMID- 21097252
TI  - In vivo measurement of human knee and hip dynamics using MIMO system
      identification.
AB  - This study presents a new method for the estimation of the dynamic impedance of
      multi-joint leg movements. The method is based on Multi Input Multi Output (MIMO)
      system identification techniques and is designed for continuous torque
      perturbations at the hip and knee joint. Preliminary results from this study
      indicate that MIMO system identification can successfully be used to estimate the
      hip and knee impedance and the interaction dynamics between both joints. It is
      also concluded that, in order to create a good model representation of the leg
      impedance, the effect of biarticular muscles needs to be taken into account. The
      obtained measures for joint impedance might be used for clinical assessment and
      follow up of patients, as well as for the development of supportive devices.

PMID- 21097253
TI  - An introduction to future truly wearable medical devices--from application to
      ASIC.
AB  - This talk will provide an introduction to the "Towards future truly wearable
      medical devices: from application to ASIC" mini-symposium. For user comfort and
      acceptance long term physiological sensors must be discrete, comfortable and easy
      to use. These requirements place stringent limits on all aspects of the system
      design: from the overall application aim, to power generation issues, to low
      power electronic design techniques. For successful devices design issues in all
      of these areas must be solved simultaneously. The work here presents an overview
      and introduction to these topics.

PMID- 21097254
TI  - Energy harvesting for human wearable and implantable bio-sensors.
AB  - There are clear trade-offs between functionality, battery lifetime and battery
      volume for wearable and implantable wireless-biosensors which energy harvesting
      devices may be able to overcome. Reliable energy harvesting has now become a
      reality for machine condition monitoring and is finding applications in chemical
      process plants, refineries and water treatment works. However, practical
      miniature devices that can harvest sufficient energy from the human body to power
      a wireless bio-sensor are still in their infancy. This paper reviews the options
      for human energy harvesting in order to determine power availability for
      harvester-powered body sensor networks. The main competing technologies for
      energy harvesting from the human body are inertial kinetic energy harvesting
      devices and thermoelectric devices. These devices are advantageous to some other
      types as they can be hermetically sealed. In this paper the fundamental limit to
      the power output of these devices is compared as a function of generator volume
      when attached to a human whilst walking and running. It is shown that the kinetic
      energy devices have the highest fundamental power limits in both cases. However,
      when a comparison is made between the devices using device effectivenesses
      figures from previously demonstrated prototypes presented in the literature, the
      thermal device is competitive with the kinetic energy harvesting device when the
      subject is running and achieves the highest power density when the subject is
      walking.

PMID- 21097255
TI  - Design considerations on ultra-low-power wireless transmitters for wearable
      medical devices.
AB  - A wireless transmitter for wearable bio-sensing applications must fulfill very
      specialized requirements. It has been estimated that for truly wearable systems
      it must operate with an average power consumption of less than 140 microW. The
      alternatives, pitfalls, and realistic performance of robust, low power signal
      transmission will be addressed.

PMID- 21097256
TI  - Low power signal processing electronics for wearable medical devices.
AB  - Custom designed microchips, known as Application Specific Integrated Circuits
      (ASICs), offer the lowest possible power consumption electronics. However, this
      comes at the cost of a longer, more complex and more costly design process
      compared to one using generic, off-the-shelf components. Nevertheless, their use
      is essential in future truly wearable medical devices that must operate for long
      periods of time from physically small, energy limited batteries. This
      presentation will demonstrate the state-of-the-art in ASIC technology for
      providing online signal processing for use in these wearable medical devices.

PMID- 21097257
TI  - Wireless EEG systems: increasing functionality, decreasing power.
AB  - Recent advances in low-power wireless technologies for health are instrumental in
      bringing EEG monitoring from the hospital to the home environment. This talk
      provides an overview of imec's research on low-power wireless EEG monitoring.
      Enabling technologies, integrated systems and remaining challenges are discussed.

PMID- 21097258
TI  - P-wave characteristics after electrical external cardioversion: predictive
      indexes of relapse.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in the western countries
      and accounts for hundred thousand strokes per year. Electrocardiographic
      characteristics of AF have been demonstrated to help identify patients at risk of
      developing AF. Prolonged and highly fragmented P-waves have been observed in
      patients prone to AF, and time-domain. Morphological characteristics of the P
      wave from surface ECG recordings turned out to significantly distinguish patients
      at risk of AF. The aim of this study is to evaluate the morphological and time
      domain characteristics of the P-wave in patients with AF relapse after
      cardioversion, respect to patients without. 14 patients who underwent successful
      electrical cardioversion for persistent AF were enrolled. Five minute ECG
      recordings were performed for each subject, immediately post-successful
      cardioversion. ECG signals were acquired by using a 16-lead mapping system for
      high-resolution biopotential measurements (sample frequency 2 kHz, 31 nV
      resolution, 0-400 Hz bandwidth). From the 16 recordings, a standard 12-lead ECG
      was derived and analyzed in terms of signal-averaged P-wave. Time-domain and mor
      phological characteristics were estimated from the averaged P-waves of each lead.
      Time-domain features were quantified as: maximum P-wave duration in any of the 12
      leads (Pmax), minimum P-wave duration in any of the leads (Pmin), P-wave
      dispersion (Pdisp=Pmax-Pmin), and Pindex (standard devia-tion of P-wave duration
      in any of the 12 leads). Morphological characteristics were extracted from a
      Gaussian function-based model of the P-wave as: average model order (Nav),
      maximum number of zero-crossing (PCmax), and maximum and average number of maxima
      and minima (FCImax and FCIav) in any of the leads. The results obtained so far
      indicate that the morphological and time-domain characteristics distinguish
      between patients with AF relapse and patients without.

PMID- 21097259
TI  - Development of artificial bionic baroreflex system.
AB  - The baroreflex system is the fastest mechanism in the body to regulate arterial
      pressure. Because the neural system (i.e., autonomic nervous system) mediates the
      baroreflex and the system operates under the closed-loop condition, the
      quantitative dynamic characteristics of the baroreflex system remained unknown
      until recently despite the fact that a countless number of observational and
      qualitative studies had been conducted. In order to develop the artificial
      baroreflex system, i.e., the bionic baroreflex system, we first anatomically
      isolated the carotid sinuses to open the baroreflex loop and identified the open
      loop transfer function of the baroreflex system using white noise pressure
      perturbations. We found that the baroreflex system is basically a lowpass filter
      and remarkably linear. As an actuator to implement the bionic baroreflex system,
      we then stimulated the sympathetic efferent nerves at various parts of the
      baroreflex loop and identified the transfer functions from the stimulation sites
      to systemic arterial pressure. We found that the actuator responses can be
      described remarkably well with linear transfer functions. Since transfer
      functions of the native baroreflex and of the actuator were identified, the
      controller that is required to reproduce the native baroreflex transfer function
      can be easily derived from those transfer functions. To examine the performance
      of bionic baroreflex system, we implemented it animal models of baroreflex
      failure. The bionic baroreflex system restored normal arterial pressure
      regulation against orthostatic stresses that is indistinguishable from the native
      baroreflex system.

PMID- 21097260
TI  - RR-SAP causality in heart transplant recipients.
AB  - An information domain approach to the assessment of causality was applied to the
      beat-to-beat variability of heart period and systolic arterial pressure to test
      the open loop condition along baroreflex in heart transplant recipients. The
      closed loop between heart period and systolic arterial pressure was detected as
      open at the level of the baroreflex if systolic arterial pressure is more easily
      predictable from heart period than vice versa according to a conditional entropy
      approach. We found that in short-term heart transplant (STHT) recipients (less
      than 2 years after transplantation) the closed loop between heart period and
      systolic arterial pressure was open at the level of baroreflex. Baroreflex
      appeared to be involved in the heart period regulation in long-term heart
      transplant (LTHT) recipients (more than 2 years after transplantation). The
      significant linear correlation of causality index on the number of months after
      transplantation suggests that baroreflex control recovers after transplantation.

PMID- 21097261
TI  - Monitoring aortic stiffness in the presence of measurement artifact based on an
      arterial tube model.
AB  - Pulse wave velocity (PWV) determined through the foot-to-foot time delay between
      carotid and femoral artery waveforms is an index of aortic stiffness with proven
      clinical value. However, handheld transducers, which are often used to non
      invasively measure the waveforms, are prone to motion artifact that may limit the
      full potential of this index. Here, we conceived an artifact robust technique to
      estimate PWV based on an arterial tube model. We applied the technique to high
      fidelity canine arterial pressure waveforms before and after contamination with
      known amounts of noise. Our results showed that, as the signal-to-noise ratio
      decreased, the PWV estimates of the technique predicted diastolic and mean
      arterial pressure with increasingly greater accuracy than the PWV estimates of
      the conventional foot-to-foot detection technique.

PMID- 21097262
TI  - Assessment of gravitational stress on heart rate variability during maneuvers on
      high performance jet flights.
AB  - The Push-Pull Effect (PPE) is a physiological phenomenon defined as a reduction
      of +Gz tolerance induced by a previous exposure to a -Gz acceleration, that may
      lead to loss of consciousness. Aim of this study was to evaluate, for the first
      time, the cardiac rhythm changes associated with PPE during real flights. Data
      were collected in 3 pilots during flights on the Aermacchi MB- 339-CD aircraft.
      In each flight, lasting about 60 minutes, ECG, respiration and 3D accelerations
      were recorded by a new smart garment (the MagIC System). The flight protocol
      included a maneuver eliciting a reference +5Gz acceleration for 15 seconds
      (Ref+5G), followed, after a while, by a push-pull maneuver with a profile
      characterized by a 5-s acceleration at -1Gz (PP-1G) and, with a 1G/s onset, by 15
      seconds at +5Gz (PP+5G), so to induce the push-pull gravitational stress. From
      each ECG recording, a beat-by-beat RR Interval (RRI) series was derived. RRI
      mean, standard deviation (SDNN) and the RRI Root Mean Square of Successive
      Difference (RMSSD) were estimated in each pilot during the Ref+5G and the PP+5G
      maneuvers. As compared with Ref+5G, all pilots displayed significant reductions
      in RRI mean, SDNN and RMSSD during PP+5G. These findings are compatible with a PP
      induced enhancement in the sympathetic drive to the heart -as shown by the
      reduction in RRI mean and SDNN- and a concomitant deactivation of the
      parasympathetic control as shown by the reduction in RMSSD.

PMID- 21097263
TI  - Performance analysis of medical video streaming over mobile WiMAX.
AB  - Wireless medical ultrasound streaming is considered one of the emerging
      application within the broadband mobile healthcare domain. These applications are
      considered as bandwidth demanding services that required high data rates with
      acceptable diagnostic quality of the transmitted medical images. In this paper,
      we present the performance analysis of a medical ultrasound video streaming
      acquired via special robotic ultrasonography system over emulated WiMAX wireless
      network. The experimental set-up of this application is described together with
      the performance of the relevant medical quality of service (m-QoS) metrics.

PMID- 21097264
TI  - Regulatory compliance requirements for an open source electronic image trial
      management system.
AB  - There is a global need for software to manage imaging based clinical trials to
      speed basic research and drug development. Such a system must comply with
      regulatory requirements. The U.S. Food and Drug Administration (FDA) has
      regulations regarding software development process controls and data provenance
      tracking. A key unanswered problem is the identification of which data changes
      are significant given a workflow model for image trial management. We report on
      the results of our study of provenance tracking requirements and define an
      architecture and software development process that meets U.S. regulatory
      requirements using open source software components.

PMID- 21097265
TI  - Low-complexity video encoding method for wireless image transmission in capsule
      endoscope.
AB  - This paper presents a low-complexity video encoding method applicable for
      wireless image transmission in capsule endoscopes. This encoding method is based
      on Wyner-Ziv theory, in which side information available at a transmitter is
      treated as side information at its receiver. Therefore complex processes in video
      encoding, such as estimation of the motion vector, are moved to the receiver
      side, which has a larger-capacity battery. As a result, the encoding process is
      only to decimate coded original data through channel coding. We provide a
      performance evaluation for a low-density parity check (LDPC) coding method in the
      AWGN channel.

PMID- 21097266
TI  - Novel joint source-channel coding for wireless transmission of radiography
      images.
AB  - A wireless technology is required to realize robust transmission of medical
      images like a radiography image over noisy environment. The use of error
      correction technique is essential for realizing such a reliable communication, in
      which a suitable channel coding is introduced to correct erroneous bits caused by
      passing through a noisy channel. However, the use of a channel code decreases its
      efficiency because redundancy bits are also transmitted with information bits.
      This paper presents a joint source-channel coding which maintains the channel
      efficiency during transmission of medical images like a radiography image. As
      medical images under the test, we use typical radiography images in this paper.
      The joint coding technique enjoys correlations between pixels of the radiography
      image. The results show that the proposed joint coding provides capability to
      correcting erroneous bits without increasing the redundancy of the codeword.

PMID- 21097267
TI  - Promoting interaction amongst autistic adolescents using robots.
AB  - Most autistic people present some difficulties in developing social behavior,
      living in their own world. The intent of this study is to improve the social life
      of adolescents with both autism and mental impairment, with a main focus on
      promoting their social interaction and communication. An experiment designed to
      call for the adolescents' attention and enforce their collaboration is described;
      in it a LEGO MindStorm robot behaves as a mediator/promotor of this interaction.
      Further, sensory motor coordination and accuracy skills of the adolescents are
      also slightly explored. Four scenarios were envisaged. Results are described
      showing the outcomes of the experiment.

PMID- 21097268
TI  - Processing of wearable sensor data on the cloud - a step towards scaling of
      continuous monitoring of health and well-being.
AB  - As part of a sleep monitoring project, we used actigraphy based on body-worn
      accelerometer sensors to remotely monitor and study the sleep-wake cycle of
      elderly staying at nursing homes. We have conducted a fifteen patient trial of a
      sleep activity pattern monitoring (SAPM) system at a local nursing home. The data
      was collected and stored in our server and the processing of the data was done
      offline after sleep diaries used for validation and ground truth were updated
      into the system. The processing algorithm matches and annotates the sensor data
      with manual sleep diary information and is processed asynchronously on the
      grid/cloud back end. In this paper we outline the mapping of the system for grid
      / cloud processing, and initial results that show expected near-linear
      performance for scaling the number of users.

PMID- 21097269
TI  - Bi-planar postural stability model: fitting model parameters to patient data
      automatically.
AB  - Postural control can be a challenging task for many people, including those with
      cerebral palsy or idiopathic scoliosis. Assessment of postural stability can be
      used as one element of a comprehensive strategy to identify more efficient
      treatments and can provide a better understanding of postural control deficits.
      Several models and techniques have been developed to assess and understand
      postural imbalance. This study presents an improvement for an existing model that
      incorporates two algorithms designed to minimize a cost function.

PMID- 21097270
TI  - sBCI: fast detection of steady-state visual evoked potentials.
AB  - Brain-computer interface (BCI) systems enable communication and control without
      movement. Although advanced signal processing methods are used in BCI research,
      the output of a BCI is still unreliable, and the information transfer rates are
      very low compared with conventional human interaction interfaces such as keyboard
      and mouse. Therefore, improvements in signal classification methods and the
      exploitation of the learning skills of the user are required to compensate the
      unreliability of the BCI system. This work analyzes the response time of the
      Bremen-BCI based on steady-state visual evoked potentials (SSVEP) previously
      tested on 27 subjects, and presents an enhanced method for faster detection of
      SSVEP responses. The aim is toward the development of a swift BCI (sBCI) that
      robustly detects the exact time point where the user starts modulating his brain
      signals.

PMID- 21097271
TI  - Investigation of muscle behavior during different functional electrical
      stimulation profiles using Mechanomyography.
AB  - Mechanomyography (MMG) is a technique for measuring muscle oscillations and
      fatigue. Functional electrical stimulation (FES) has been applied to control
      movements mainly in people with spinal cord injury (SCI). The goal of this study
      is the application of the MMG signal as a tool to investigate muscle response
      during FES. Ten healthy individuals (HI) and three SCI were submitted to four FES
      profiles in the rectus femoris (RF) and vastus lateralis (VL) muscles. Four FES
      profiles were applied in different days. The FES profile set to 1 kHz pulse
      frequency, 200 us active pulse duration and burst frequency of 50 Hz presented
      the lowest MMG root mean square and spectral median frequency values, suggesting
      less muscle modification. The MMG signal was different between HI and SCI but
      there was no difference between the RF and VL muscles.

PMID- 21097272
TI  - A fuzzy logic-based system for anaesthesia monitoring.
AB  - In recent years there has been a rapid growth in patient monitoring and medical
      data analysis using a number of computer-aided systems based on expert systems,
      fuzzy logic and many other intelligent techniques. Fuzzy logic-based expert
      systems have shown potential to improve clinician performance by imitating human
      thought processes in complex circumstances and accurately executing repetitive
      tasks to which humans are ill-suited. The main goal of this study was to develop
      a clinically useful diagnostic alarm system for detecting critical events during
      anaesthesia administration. The proposed diagnostic alarm system called Fuzzy
      logic monitoring system (FLMS) is presented. The performance of the system was
      validated through a series of off-line tests. When detecting hypovolaemia a
      substantial level of agreement was observed between FLMS and the human expert
      (the anaesthetist) during surgical procedures.

PMID- 21097273
TI  - Application of crisp and fuzzy clustering algorithms for identification of hidden
      patterns from plethysmographic observations on the radial pulse.
AB  - Radial Pulse forms the most basic and essential physical sign in clinical
      medicine. The paper proposes the application of crisp and fuzzy clustering
      algorithms under supervised and unsupervised learning scenarios for identifying
      non-trivial regularities and relationships of the radial pulse patterns obtained
      by using the Impedance Plethysmographic technique. The objective of our paper is
      to unearth the hidden patterns to capture the physiological variabilities from
      the arterial pulse for clinical analysis, thus providing a very useful tool for
      disease characterization. A variety of fuzzy algorithms including Gustafson
      Kessel (GK) and Gath-Geva (GG)have been intensively tested over a diverse group
      of subjects and over 4855 data sets. Exhaustive testing over the data set show
      that about 80 % of the patterns are successfully classified thus providing
      promising results. A Rank Index of 0.7739 is obtained under supervised learning,
      which provides an excellent conformity of our process with the results of
      plethysmographic experts. A correlation of the patterns with the diseases of
      heart, liver and lungs is judiciously performed.

PMID- 21097274
TI  - Characterization of bone tissue using microstrip antennas.
AB  - The use of electromagnetic waves in the characterization of biological tissues
      has been conducted since the nineteenth century after the confirmation that
      electric and magnetic fields can interact with biological materials. In this
      paper, electromagnetic waves are used to characterize tissues with different
      levels of bone mass. In this way, one antenna array on microstrip lines was used.
      It can be seen that bones with different mass has different behavior in microwave
      frequencies.

PMID- 21097275
TI  - Clustering evoked potential signals using subspace methods.
AB  - This work proposes a clustering technique to analyze evoked potential signals.
      The proposed method uses an orthogonal subspace model to enhance the single-trial
      signals of a session and simultaneously a subspace measure to group the trials
      into clusters. The ensemble averages of the signals of the different clusters are
      compared with ensemble averages of visually selected trials which are free of any
      artifact. Preliminary results consider recordings from an occipital channel where
      evoked response P100 wave is most pronounced.

PMID- 21097276
TI  - An energy ratio based measure for F-wave backfiring rate estimation.
AB  - F-wave persistence is a frequently reported parameter for nerve conduction
      studies. F-wave activities are generated through backfiring of motor neurons. F
      wave persistence is designed to estimate the backfiring rate. Through
      computational models and probability analyses, we demonstrated that the F-wave
      persistence definition is deficient in providing a robust and consistent estimate
      of the backfiring rate. We proposed an energy ratio based measure as an
      alternative to F-wave persistence to estimate backfiring rates. The energy ratio
      measure is shown to be robust to activity detection threshold and without the
      ceiling effect suffered by the traditional F-wave persistence.

PMID- 21097277
TI  - Evaluation of the sleep quality based on bed sensor signals: Time-variant
      analysis.
AB  - Automatic detection of the sleep macrostructure (Wake, NREM -non Rapid Eye
      Movement- and REM -Rapid Eye Movement-) based on bed sensor signals is presented.
      This study assesses the feasibility of different methodologies to evaluate the
      sleep quality out of sleep centers. The study compares a) the features extracted
      from time-variant autoregressive modeling (TVAM) and Wavelet Decomposition (WD)
      and b) the performance of K-Nearest Neighbor (KNN) and Feed Forward Neural
      Networks (FFNN) classifiers. In the current analysis, 17 full polysomnography
      recordings from healthy subjects were used. The best agreement for Wake-NREM-REM
      with respect to the gold standard was 71.95 +/- 7.47% of accuracy and 0.42 +/-
      0.10 of kappa index for TVAM-LD while WD-FFNN shows 67.17 +/- 11.88% of accuracy
      and 0.39 +/- 0.13 of kappa index. The results suggest that the sleep quality
      assessment out of sleep centers could be possible and as consequence more people
      could be beneficiated.

PMID- 21097278
TI  - Feature analysis of epileptic EEG using nonlinear prediction method.
AB  - We propose a feature extraction method based on the Volterra autoregressive
      model's prediction power and the data's predictability for the EEG signals to
      automatically detect the epileptic EEG signals from the EEG recordings. The
      method of determining the embedding dimension based on nonlinear prediction is
      applied to choose the embedding dimension of the EEG data. The proposed feature
      extraction method is used to extract the feature for three groups of EEG time
      series composing epileptic seizure. We divide the EEG data into segments, and
      respectively compute the feature values of each segment, where the length of data
      segment respectively takes the value of 250, 500, 1000 points. To investigate the
      robustness of our method under noises, we also analyze the three EEG time series
      with additive white Gaussian noise. The experiment results show that the feature
      values extracted with the proposed method could obviously distinguish the
      epileptic EEG signals from the normal EEG signals. The proposed method is
      effective for short time series, insensitive to the length of data segment, and
      robust to the additive white noise, and it could differentiate the epileptic EEG
      from the normal EEG when the signal-to-noise ratio is low.

PMID- 21097279
TI  - Quantifying electrode position effects in EEG data with Lempel-Ziv complexity.
AB  - Complexity measurement using Lempel and Ziv algorithm (LZ) has been used to
      analyze physiological data. This work shows that the Lempel and Ziv complexity
      measurement of EEG signals using wavelets transforms is independent of electrode
      position and dependent on cognitive tasks and brain activity. EEG database with
      122 subjects from the public EEG dataset was used in this study. This database
      have spontaneous EEG and evoked potential (EP) data from a 64-multielectrode
      array under a variety of conditions collected at several centers in the United
      States, sponsored by the National Institute on Alcohol Abuse and Alcoholism
      (NIAAA) project. Two experiments were performed with this database. The first
      experiment was to test the dependency of electrode positions into LZ complexity
      measures and the second experiment was to analyze if the LZ complexity was
      sensitive to the EEG acquired from control and alcoholic subjects. The results
      show that the complexity measurement is dependent on the changes of the pattern
      of brain dynamics and not dependent on electrode position.

PMID- 21097280
TI  - Diagnosis of psychiatric disorders using EEG data and employing a statistical
      decision model.
AB  - An automated diagnosis procedure based on a statistical machine learning
      methodology using electroencephalograph (EEG) data is proposed for diagnosis of
      psychiatric illness. First, a large collection of candidate features, mostly
      consisting of various statistical quantities, are calculated from the subject's
      EEG. This large set of candidate features is then reduced into a much smaller set
      of most relevant features using a feature selection procedure. The selected
      features are then used to evaluate the class likelihoods, through the use of a
      mixture of factor analysis (MFA) statistical model [7]. In a training set of 207
      subjects, including 64 subjects with major depressive disorder (MDD), 40 subjects
      with chronic schizophrenia, 12 subjects with bipolar depression and 91 normal or
      healthy subjects, the average correct diagnosis rate attained using the proposed
      method is over 85%, as determined by various cross-validation experiments. The
      promise is that, with further development, the proposed methodology could serve
      as a valuable adjunctive tool for the medical practitioner.

PMID- 21097281
TI  - Reduction of irrelevant and redundant data from TFRs for EEG signal
      classification.
AB  - Time-frequency representations (TFR) are one of the most popular characterization
      methods for non-stationary biosignals. Despite of their potential advantages,
      these representations suffer of large quantity of redundant and irrelevant data
      which makes them difficult to use for classification purposes. In this work, a
      methodology for reduction of irrelevant and redundant data is explored. This
      approach consists on removing irrelevant data, applying a relevance measure on
      the t-f plane that measures the dependence of each t-f point with the class
      labels. Then, principal component analysis (PCA) and partial least squares (PLS)
      are used as non-supervised and supervised linear decomposition approaches to
      reduce redundancy of remaining t-f points. Results show that the proposed
      methodology improves the performance of classifier up to 3% when no relevance and
      redundancy on TFRs is reduced.

PMID- 21097282
TI  - Consistent sparse representations of EEG ERP and ICA components based on wavelet
      and chirplet dictionaries.
AB  - A randomized search algorithm for sparse representations of EEG event-related
      potentials (ERPs) and their statistically independent components is presented.
      This algorithm combines greedy matching pursuit (MP) technique with covariance
      matrix adaptation evolution strategy (CMA-ES) to select small number of signal
      atoms from over-complete wavelet and chirplet dictionaries that offer best
      approximations of quasi-sparse ERP signals. During the search process, adaptive
      pruning of signal parameters was used to eliminate redundant or degenerative
      atoms. As a result, the CMA-ES/MP algorithm is capable of producing accurate
      efficient and consistent sparse representations of ERP signals and their ICA
      components. This paper explains the working principles of the algorithm and
      presents the preliminary results of its use.

PMID- 21097283
TI  - Wavelet transform and cross-correlation as tools for seizure prediction.
AB  - This paper describes the detection of preictal bursting using wavelet transform
      application and cross-correlation analysis. The wavelet transform is applied to
      data reduction and signal pre-processing. The extracted features provide
      simplified signals to process by means of the cross-correlation technique. The
      algorithm has been tested with a set of preictal data, interictal data and
      spontaneous crises, to determinate its sensitivity and its specificity (False
      Prediction Rate). The seizure occurrence period and the seizure prediction
      horizon are also calculated. The algorithm's merits are: 1) high sensitivity and
      2) easy implementation.

PMID- 21097284
TI  - Rats hippocampal field potentials feature extraction of wake and sleep stages in
      Euclidean space.
AB  - This paper presents a new methodology of feature extraction of sleep and wake
      stages of a freely behaving rat based on Continuous Wavelet Transform (CWT). The
      automatic separation of those stages is very useful for experiments related to
      learning and memory consolidation since recent scientific evidence indicates that
      sleep is strongly involved with offline reprocessing of acquired information
      during waking. Our approach transforms hippocampal Local Field Potentials (LFP)
      in data vectors that describe the energy distribution pattern of the signal on
      scaled Morlet wavelets projections. Results indicate that the mathematical
      analysis used in this work can sensibly describe brain signal patterns that
      correlate to states of behaviour and that our method can be used for a wider
      range of applications in neuroscience research.

PMID- 21097285
TI  - Fractional fourier-based filter for denoising elastograms.
AB  - In ultrasound elastography, tissue axial strains are obtained through the
      differentiation of axial displacements. However, the application of the gradient
      operator amplifies the noise present in the displacement rendering unreadable
      axial strains. In this paper a novel denoising scheme based on repeated filtering
      in consecutive fractional Fourier transform domains is proposed for the accurate
      estimation of axial strains. The presented method generates a time-varying cutoff
      threshold that can accommodate the discrete non-stationarities present in the
      displacement signal. This is achieved by means of a filter circuit which is
      composed of a small number of ordinary linear low-pass filters and appropriate
      fractional Fourier transforms. We show that the proposed method can improve the
      contrast-to-noise ratio (CNR(e)) of the elastogram outperforming conventional low
      pass filters.

PMID- 21097286
TI  - On detecting determinism and nonlinearity in microelectrode recording signals:
      approach based on non-stationary surrogate data methods.
AB  - Two new surrogate methods, the Small Shuffle Surrogate (SSS) and the Truncated
      Fourier Transform Surrogate (TFTS), have been proposed to study whether there are
      some kind of dynamics in irregular fluctuations and if so whether these dynamics
      are linear or not, even if this fluctuations are modulated by long term trends.
      This situation is theoretically incompatible with the assumption underlying
      previously proposed surrogate methods. We apply the SSS and TFTS methods to
      microelectrode recording (MER) signals from different brain areas, in order to
      acquire a deeper understanding of them. Through our methodology we conclude that
      the irregular fluctuations in MER signals possess some determinism.

PMID- 21097287
TI  - STFT-based denoising of biomechanical impact signals.
AB  - We present an advanced denoising method for non-stationary biomechanical signals
      with the aim of accurately estimating their second derivative (acceleration). The
      proposed algorithm is based on the short-time Fourier transform (STFT)
      representation of the signal and its subsequent modification by means of a
      suitable time-varying filtering function. The application of the method to
      experimentally acquired biomechanical signals demonstrated that the proposed
      algorithm is more robust against noise and achieves a more accurate acceleration
      peak estimation as compared to commonly used conventional low-pass filtering.

PMID- 21097288
TI  - Towards high accuracy classification of MER signals for target localization in
      Parkinson's disease.
AB  - In recent years Microelectrode recording (MER) analysis has proved to be a
      powerful localization tool of basal ganglia for Parkinson disease's treatment,
      especially the Subthalamic Nucleus (STN). In this paper, a signal-dependent
      method is presented for identification of the STN and other brain zones in
      Parkinsonian patients. The proposed method, refereed as optimal wavelet feature
      extraction method (OWFE), is constructed by lifting schemes (LS), which are a
      flexible and fast implementation of the wavelet transform (WT). The operators in
      the LS are optimized by means of Genetic Algorithms and Lagrange multipliers
      considering information contained in MER signals. Then a basic Bayesian
      classifier (LDC) is used to identify STN and other types of basal ganglia nuclei.
      The proposed method introduced several advantages from similar works reported in
      literature. First, the method is signal-dependent and non a priori information is
      required to decompose the MER signal. Second, the classification accuracy is
      mostly depended on the feature selection stage because it is not enhanced by
      elaborated classifiers such as support vector machines or hidden Markov models.
      Finally, the generalization property of the OWFE has been validated with two
      databases and different types of classifiers such as k-NN classifier and
      quadratic Bayesian classifier (QDC). Results have shown that proposed method is
      able to identify the STN with average accuracy superior than 97%.

PMID- 21097289
TI  - Dynamic speech parameterization for text-independent phone segmentation.
AB  - In this work, a dynamic speech parameterization based on the continuous
      multiresolution divergence is used to modify a text-independent phone
      segmentation algorithm. This encoding is employed as input and also replaces an
      stage of the segmentation procedure responsible for the estimation of the
      intensity of changes in signal features. The segmentation performance of this
      representation has been compared with the original algorithm using as input a
      classical Melbank parameterization and speech representation based on the
      continuous multiresolution divergence. The results indicate that the modification
      here proposed increases the ability of the algorithm to perform the segmentation
      task. This suggests that continuous multiresolution divergence provides valuable
      information related to acoustic features that take into account phoneme
      transitions. Moreover, this parameterization gives enough information for its
      direct use without further processing.

PMID- 21097290
TI  - Temporal segmentation of lung region MR image sequences using hough transform.
AB  - In this work, segmentation is an intermediate step in the registration and 3D
      reconstruction of the lung, where the diaphragmatic surface is automatically and
      robustly isolated. Usually, segmentation methods are interactive and use
      different strategies to combine the expertise of humans and computers.
      Segmentation of lung MR images is particularly difficult because of the large
      variation in image quality. The breathing is associated to a standard respiratory
      function, and through 2D image processing, edge detection and Hough transform,
      respiratory patterns are obtained and, consequently, the position of points in
      time are estimated. Temporal sequences of MR images are segmented by considering
      the coherence in time. This way, the lung silhouette can be determined in every
      frame, even on frames with obscure edges. The lung region is segmented in two
      steps: a mask containing the lung region is created, and the Hough transform is
      applied exclusively to mask pixels. The shape of the mask can have a large
      variation, and the modified Hough transform can handle such shape variation. The
      result was checked through temporal registration of coronal and sagittal images.

PMID- 21097291
TI  - An improved gradient vector flow algorithm for optic disc segmentation.
AB  - The optic disc provides important cues for accurate diagnosis of various
      retinopathic diseases. Accurate segmentation of the optic disc is therefore an
      important step in the analysis of retinal images. Gradient vector flow (GVF)
      based segmentation algorithms have been used successfully on a variety of medical
      imagery, however, due to the compromise of internal and external energy forces,
      it can lead to less accurate segmentation in certain cases. In this paper, we
      show, that through incorporation of a mean shift term into the GVF framework,
      improved segmentation accuracy can be achieved. Experimental results on a large
      dataset of retinal images demonstrate that the presented method reliably detects
      the border of the optic disc.

PMID- 21097292
TI  - Efficient liver surgery planning in 3D based on functional segment classification
      and volumetric information.
AB  - Anatomic hepatectomies are resections in which compromised segments or sectors of
      the liver are extracted according to the topological structure of its vascular
      elements. Such structure varies considerably among patients, which makes the
      current anatomy-based planning methods often inaccurate. In this work we propose
      a strategy to efficiently and semi-automatically segment and classify patient
      specific liver models in 3D. The method is based on standard CT datasets and
      allows accurate estimation of functional remaining liver volume. Experiments
      showing effectiveness of the method are presented, and quantitative and
      qualitative results are discussed.

PMID- 21097293
TI  - Detecting tubular structures via direct vector field singularity
      characterization.
AB  - The initial step of vessel segmentation in 3D is the detection of vessel
      centerlines. The proposed methods in literature are either dependent on vessel
      radius and/or have low response at vessel bifurcations. In this paper we propose
      a 3D tubular structure detection method that removes these two drawbacks. The
      proposed method exploits the observations on the eigenvalues of the Hessian
      matrix as is done in literature, yet it employs a direct 3D vector field
      singularity characterization. The Gradient Vector Flow vector field is used and
      the eigenvalues of its Jacobian are exploited in computing a parameter free
      vesselness map. Results on phantom and real patient data exhibit robustness to
      scale, high response at vessel bifurcations, and good noise/non-vessel structure
      suppression.

PMID- 21097294
TI  - Decoupled external forces in a predictor-corrector segmentation scheme for LV
      contours in Tagged MR images.
AB  - Computation of functional regional scores requires proper identification of LV
      contours. On one hand, manual segmentation is robust, but it is time consuming
      and requires high expertise. On the other hand, the tag pattern in TMR sequences
      is a problem for automatic segmentation of LV boundaries. We propose a
      segmentation method based on a predictor-corrector (Active Contours - Shape
      Models) scheme. Special stress is put in the definition of the AC external
      forces. First, we introduce a semantic description of the LV that discriminates
      myocardial tissue by using texture and motion descriptors. Second, in order to
      ensure convergence regardless of the initial contour, the external energy is
      decoupled according to the orientation of the edges in the image potential. We
      have validated the model in terms of error in segmented contours and accuracy of
      regional clinical scores.

PMID- 21097295
TI  - Improved Gradient Vector Flow for robust shape estimation in medical imaging.
AB  - We propose a improved Gradient Vector Flow (iGVF) for active contour detection.
      The algorithm herein proposed allows to surpass the problems of the GVF, which
      occur in noisy images with cluttered background. We experimentally illustrate
      that the proposed modified version of the GVF algorithm has a better performance
      in noisy images. The main difference concerns the use of more robust and
      informative features (edge segments) which significantly reduce the influence of
      noise. Experiments with real data from several image modalities are presented to
      illustrate the performance of the proposed approach.

PMID- 21097296
TI  - Segmentation of cell clumps for quantitative analysis.
AB  - The increasing amounts of microscopy data generated in cell biology requires the
      development of automated tools for the quantitative analysis of images. Clumps of
      cells are difficult to segment due to the frequent lack of clear boundaries
      between cells and are often ignored, but communication between cells is an
      intrinsic part of the response of cells to their environment. In addition cells
      often show a large variation in their responses, even within a clump, and an
      accurate segmentation is therefore vital to prevent the unwanted averaging of
      measurements over multiple cells. Here we present a method for segmenting clumps
      of cells by using a multi-scale ridge filter to enhance unclear boundaries. A
      multi-phase level set method incorporating a region competition term is used to
      identify a boundary for each cell based on the ridge filter response.

PMID- 21097297
TI  - Mixture model-based approach for optic cup segmentation.
AB  - Glaucoma is a leading cause of blindness with permanent damage to optic nerve
      head. ARGALI is an automated computer-aided diagnosis system designed for
      glaucoma detection via optic cup-to-disc ratio assessment. It employs several
      methods to determine the optic cup and disc from retinal images.

PMID- 21097298
TI  - A machine learning based method for classification of fractal features of forearm
      sEMG using Twin Support vector machines.
AB  - Classification of surface electromyogram (sEMG) signal is important for various
      applications such as prosthetic control and human computer interface. Surface EMG
      provides a better insight into the strength of muscle contraction which can be
      used as control signal for different applications. Due to the various
      interference between different muscle activities, it is difficult to identify
      movements using sEMG during low-level flexions. A new set of fractal features -
      fractal dimension and Maximum fractal length of sEMG has been previously reported
      by the authors. These features measure the complexity and strength of the muscle
      contraction during the low-level finger flexions. In order to classify and
      identify the low-level finger flexions using these features based on the fractal
      properties, a recently developed machine learning based classifier, Twin Support
      vector machines (TSVM) has been proposed. TSVM works on basic learning
      methodology and solves the classification tasks as two SVMs for each classes.
      This paper reports the novel method on the machine learning based classification
      of fractal features of sEMG using the Twin Support vector machines. The training
      and testing was performed using two different kernel functions - Linear and
      Radial Basis Function (RBF).

PMID- 21097299
TI  - Time robust movement direction decoding in Local Field Potentials using channel
      ranking.
AB  - Movement direction for Brain Machine Interface (BMI) can be decoded successfully
      using Local Field Potentials (LFP) and Single Unit Activity (SUA). A major
      challenge when dealing with the intra-cortical recordings is to develop decoders
      that are robust in time. In this paper we present for the first time a technique
      that uses the qualitative information derived from multiple LFP channels rather
      than the absolute power of the recorded signals. In this novel method, we use a
      power based inter-channel ranking system to define the quality of a channel in
      multi-channel LFP. This representation enables us to bypass the problems
      associated with the dynamic ranges of absolute power. We also introduce a
      parameter based ranking system that provides the same rank to channels that have
      comparable powers. We show that using our algorithms, we can develop models that
      provide stable decoding of eight movement directions with an average efficiency
      of above 56% over a period of two weeks. Moreover, the decoding power using this
      method is 46% at the end of two weeks versus the 13% using the traditional
      approaches. We also applied these models to decoding movements performed in a
      force field and again achieved significantly higher decoding power than the
      existing methods.

PMID- 21097300
TI  - The excitation functional for magnetic stimulation of fibers.
AB  - Threshold problems in electric stimulation of nerve and muscle fibers have been
      studied from a theoretical standpoint using the excitation functional. Here the
      excitation functional is extended to magnetic stimulation of excitable nerve and
      muscle fibers. A unified derivation of the functional is done, for (non
      myelinated) nerve and muscle fibers, by means of the nonlinear cable equation
      with a Fitzhugh-Nagumo membrane model and a generalized Rattay's activating
      function. The identification problem of the excitation functional for magnetic
      stimulation, from strength-duration experimental data, is briefly considered.

PMID- 21097301
TI  - The minimum interval for confident spike sorting: A sequential decision method.
AB  - This paper develops a method to determine the minimum duration interval which
      ensures that the process of "sorting" the extracellular action potentials
      recorded during that interval achieves a desired confidence level of accuracy.
      During the recording process, a sequential decision theory approach continually
      evaluates a variant of the likelihood ratio test using the model evidence of the
      sorting/clustering hypotheses. The test is compared against a threshold which
      encodes a desired confidence level on the accuracy of the subsequent clustering
      procedure. When the threshold is exceeded, the clustering model with the highest
      model evidence is accepted. We first develop a testing procedure for a single
      recording interval, and then extend the method to multi-interval recording by
      using both Bayesian priors from previous recording intervals and recently
      developed cluster tracking procedure. Lastly, a more advanced tracker is
      implemented and initials results are presented. This later procedure is useful
      for real time applications such as brain machine interfaces and autonomous
      recording electrodes. We test our theory on recordings from Macaque parietal
      cortex, showing that the method does reach the desired confidence level.

PMID- 21097303
TI  - FMRI 3D registration based on Fourier space subsets using neural networks.
AB  - In this work, we present a neural network (NN) based method designed for 3D rigid
      body registration of FMRI time series, which relies on a limited number of
      Fourier coefficients of the images to be aligned. These coefficients, which are
      comprised in a small cubic neighborhood located at the first octant of a 3D
      Fourier space (including the DC component), are then fed into six NN during the
      learning stage. Each NN yields the estimates of a registration parameter. The
      proposed method was assessed for 3D rigid-body transformations, using DC
      neighborhoods of different sizes. The mean absolute registration errors are of
      approximately 0.030 mm in translations and 0.030 deg in rotations, for the
      typical motion amplitudes encountered in FMRI studies. The construction of the
      training set and the learning stage are fast requiring, respectively, 90 s and 1
      to 12 s, depending on the number of input and hidden units of the NN. We believe
      that NN-based approaches to the problem of FMRI registration can be of great
      interest in the future. For instance, NN relying on limited K-space data
      (possibly in navigation echoes) can be a valid solution to the problem of
      prospective (in frame) FMRI registration.

PMID- 21097302
TI  - Study of neuronal networks development from in-vitro recordings: A Granger
      causality based approach.
AB  - This methodological work is aimed at providing a Granger causality based approach
      to the study of neuronal networks development in vitro. The analysis procedure
      makes use of tools derived from statistics and network theory for accessing
      network development of in-vitro neuronal cultures from their electrical activity,
      recorded through Multi Electrode Arrays (MEAs). The preliminary results that will
      be presented here show the potential of this approach for characterizing in a
      quantitative way the developmental stages of neuronal networks and provide some
      evidences which are consistent with direct in-vitro and in-vivo observations
      reported by other authors.

PMID- 21097304
TI  - A torsional eye movement calculation algorithm for low contrast images in video
      oculography.
AB  - Video-oculography (VOG) is a frequently used clinical technique to detect eye
      movements. In this research, head mounted small video-cameras and IR-illumination
      are employed to image the eye. Many algorithms have been developed to extract
      horizontal and vertical eye movements from the video images. Designing a method
      to determine torsional eye movements is a more complex task. The use of IR
      wavelengths required for illumination in certain clinical tests results in a very
      low image contrast. In such images, iris textures are almost invisible, making
      them unsuited for direct application of standard matching algorithms, which are
      used to calculate torsional eye movements. This research presents the design and
      implementation of a robust torsional eye movement detection algorithm for VOG.
      This algorithm uses a new approach to measure the torsional eye movement and is
      suitable for low contrast videos. The algorithm is implemented in a clinical
      device and its performance is compared to that of alternative techniques.

PMID- 21097305
TI  - Analysis of foveal avascular zone in colour fundus images for grading of diabetic
      retinopathy severity.
AB  - Diabetic retinopathy (DR) is a sight threatening complication due to diabetes
      mellitus that affects the retina. At present, the classification of DR is based
      on the International Clinical Diabetic Retinopathy Disease Severity. In this
      paper, FAZ enlargement with DR progression is investigated to enable a new and an
      effective grading protocol DR severity in an observational clinical study. The
      performance of a computerised DR monitoring and grading system that digitally
      analyses colour fundus image to measure the enlargement of FAZ and grade DR is
      evaluated. The range of FAZ area is optimised to accurately determine DR severity
      stage and progression stages using a Gaussian Bayes classifier. The system
      achieves high accuracies of above 96%, sensitivities higher than 88% and
      specificities higher than 96%, in grading of DR severity. In particular, high
      sensitivity (100%), specificity (>98%) and accuracy (99%) values are obtained for
      No DR (normal) and Severe NPDR/PDR stages. The system performance indicates that
      the DR system is suitable for early detection of DR and for effective treatment
      of severe cases.

PMID- 21097306
TI  - Automated indexation of metabolic changes in Alzheimer's mice using a voxel-wise
      approach combined to an MRI-based 3D digital atlas.
AB  - Brain glucose uptake was examined in transgenic mice relevant to Alzheimer's
      disease (APP/PS1) and their control littermates (PS1). Glucose distribution in
      the brain of the resting animals was measured using 3D-reconstructed
      autoradiography and analysed by a voxel-wise approach using SPMMouse combined to
      an MRI-based 3D digital atlas. Prompt and direct indexation of metabolic changes
      between the two groups was achieved, showing both hypo- and hypermetabolism of
      glucose in the brain of APP/PS1 mice. We confirm and extend previous study, since
      we identified brain structures affected in this pathological model and
      demonstrate glucose uptake changes in structures like the olfactory bulb. Our
      results pave the way to complete and accurate examination of functional data from
      cerebral structures involved in models of neurodegenerative diseases.

PMID- 21097307
TI  - fMRI measurement of brain activities to major and minor chords and cadence
      sequences.
AB  - Brain activities to major and minor chords and to major and minor cadence
      sequences were measured by sparse scanning fMRI. Areas activated by major and
      minor chords and cadence sequences were examined. Some of them are known to be
      related to emotion, motivation, arousal or reward. In general, minor chords
      activated larger areas of brain regions than major chords. Some activated areas
      have not been especially associated with emotion or music processing. Cadence
      results are somewhat ambiguous probably due to the control sequence used. Also
      individual differences were considerable in both experiments.

PMID- 21097308
TI  - Automatic blood vessel localization in small field of view eye images.
AB  - Localizing blood vessels in eye images is a crucial step in the automated and
      objective diagnosis of eye diseases. Most previous research has focused on
      extracting the centerlines of vessels in large field of view images. However, for
      diagnosing diseases of the optic disk region, like glaucoma, small field of view
      images have to be analyzed. One needs to identify not only the centerlines, but
      also vessel widths, which vary widely in these images. We present an automatic
      technique for localizing vessels in small field of view images using multi-scale
      matched filters. We also estimate local vessel properties - width and orientation
      - along the length of each vessel. Furthermore, we explicitly account for
      highlights on thick vessels - central reflexes - which are ignored in many
      previous works. Qualitative and quantitative results demonstrate the efficacy of
      our method - e.g. vessel centers are localized with RMS and median errors of 2.11
      and 1 pixels, respectively in 700*700 images.

PMID- 21097309
TI  - Support system for the preventive diagnosis of hypertensive retinopathy.
AB  - The changes in diameter of retinal vessels are an important sign of diseases such
      as hypertension, arteriosclerosis and diabetes. Obtaining precise measurements of
      vascular widths is a critical and demanding process in automated retinal image
      analysis. This paper presents the development of a prototype for measuring the
      vessel diameters to calculate the arteriovenous ratio (AVR) by using different
      techniques including Gabor wavelet, gradients, morphological operations and
      Niblack. The diameter measurement is based on the image skeleton and the
      perpendicular segment of the vessel. An executable tool is developed using MATLAB
      and the results are evaluated.

PMID- 21097310
TI  - Automatic immunostaining vessel image filtering for visual search efficiency.
AB  - Blood vessel abstraction is an important procedure for quantitative analysis of
      blood vessel densities determined by immunostaining the tumor cells. Due to the
      weak contrast of object boundaries and background clutter, it is difficult to
      identify the vessel and non-vessel region clearly. In this paper we present a
      novel algorithm to automatically abstract salient regions in blood vessel images
      using Gaussian perceptually color space for producing the detail and large-scale
      layer. The first component of Gaussian color model is used to represent the large
      scale layer after bilateral filtering. The detail layer of salient region in the
      blood vessel image is obtained by normalizing the color of the color layer in the
      image. Using these two features, we can reconstruct the image using intensity
      color coupling. The abstraction result is then processed by luminance
      quantization algorithm to provide both boundary and region information of blood
      vessel images. This proposed algorithm has been applied on a wide range of
      complex blood vessel images with promising results.

PMID- 21097311
TI  - A robust volumetric feature extraction approach for 3D neuroimaging retrieval.
AB  - The increased volume of 3D neuroimaging data has created a need for efficient
      data management and retrieval. We suggest that image retrieval via robust
      volumetric features could benefit managing these large image datasets. In this
      paper, we introduce a new feature extraction method, based on disorder-oriented
      masks, that uses the volumetric spatial distribution patterns in 3D physiological
      parametric neurological images. Our preliminary results indicate that the
      proposed volumetric feature extraction approach could support reliable 3D
      neuroimaging data retrieval and management.

PMID- 21097313
TI  - Tractography clustering for fiber selection in ROI-based diffusion tensor
      studies.
AB  - Estimating white matter ber pathways from a diffusion tensor MRI dataset has many
      important applications in medical research. Even after the definition of white
      matter ROIs, the precise selection of appropriate fibers of interest for further
      analysis in population studies is often a time consuming and error prone task.
      Tractography segmentation methods based on pairwise distances between fibers are
      computationally expensive and have limitations addressing this problem. This
      paper proposes a new method to automatically perform fiber tract selection for
      ROI-based tractography analysis. The tractography segmentation is based on the
      representation of the fibers by means of their orientation at the closest point
      to the centroid of the associated ROI. Results and comparisons on two real-world
      fiber tract selection problems show the proposed method to constitute a simple
      yet effective tool for addressing this important problem.

PMID- 21097312
TI  - Comparison and analysis of nonlinear algorithms for compressed sensing in MRI.
AB  - Compressed sensing (CS) theory has been recently applied in Magnetic Resonance
      Imaging (MRI) to accelerate the overall imaging process. In the CS
      implementation, various algorithms have been used to solve the nonlinear equation
      system for better image quality and reconstruction speed. However, there are no
      explicit criteria for an optimal CS algorithm selection in the practical MRI
      application. A systematic and comparative study of those commonly used algorithms
      is therefore essential for the implementation of CS in MRI. In this work, three
      typical algorithms, namely, the Gradient Projection For Sparse Reconstruction
      (GPSR) algorithm, Interior-point algorithm (l(1)_ls), and the Stagewise
      Orthogonal Matching Pursuit (StOMP) algorithm are compared and investigated in
      three different imaging scenarios, brain, angiogram and phantom imaging. The
      algorithms' performances are characterized in terms of image quality and
      reconstruction speed. The theoretical results show that the performance of the CS
      algorithms is case sensitive; overall, the StOMP algorithm offers the best
      solution in imaging quality, while the GPSR algorithm is the most efficient one
      among the three methods. In the next step, the algorithm performances and
      characteristics will be experimentally explored. It is hoped that this research
      will further support the applications of CS in MRI.

PMID- 21097314
TI  - Low-parametric induced current - magnetic resonance electrical impedance
      tomography for quantitative conductivity estimation of brain tissues using a
      priori information: a simulation study.
AB  - Accurate estimation of the human head conductivity is important for the diagnosis
      and therapy of brain diseases. Induced Current - Magnetic Resonance Electrical
      Impedance Tomography (IC-MREIT) is a recently developed non-invasive technique
      for conductivity estimation. This paper presents a formulation where a low number
      of material parameters need to be estimated, starting from MR eddy-current field
      maps. We use a parameterized frequency dependent 4-Cole-Cole material model, an
      efficient independent impedance method for eddy-current calculations and a priori
      information through the use of voxel models. The proposed procedure circumvents
      the ill-posedness of traditional IC-MREIT and computational efficiency is
      obtained by using an efficient forward eddy-current solver.

PMID- 21097315
TI  - fMRI headtracking using a single camera and a lightweight fiducial.
AB  - A single CCD/DSP camera based optical system affords six degree of freedom motion
      tracking for MRI applications with resolutions in the range of < 50 microradians
      and 10-100 microns. The fiducial target is a lightweight compact three
      dimensional pattern that allows efficient, centroid based algorithms to determine
      distance translation and angle rotation at rates of 30Hz. In-magnet tests measure
      the inherent magnet vibration as well as subject signatures such as those for
      respiration, speech, swallow and nod.

PMID- 21097316
TI  - On the distinguishability of HRF models in fMRI.
AB  - The problem of model falsification or model invalidation appears in several areas
      where we are interested in distinguishing among an eligible set of dynamic
      systems. In the context of fMRI studies of brain activity, modeling the
      haemodynamic response function (HRF) is a critical step. The estimation of the
      dynamic system describing a biophysical model of the HRF may leave much
      uncertainty on the exact values of the parameters. Moreover, the high noise
      levels in the data may hinder the model identification task. Therefore, this
      paper proposes a systematic tool to address the problem of the distinguishability
      among a set of physiologically plausible HRF models. The concept of absolutely
      input distinguishable systems is introduced and applied to the HRF model, by
      exploiting the structure of the underlying nonlinear dynamic system. A strategy
      to model uncertainty in the input time delay and magnitude is developed and its
      impact on the distinguishability of two physiologically plausible HRF models is
      determined, in terms of the maximum noise amplitude above which it is not
      possible to guarantee the falsification of one model in relation to the other.
      Finally, a methodology is proposed for the choice of the input sequence, or
      experimental paradigm, that should be used in order to maximize the
      distinguishability of the HRF models under investigation. The proposed approach
      may be used to assess the performance of HRF model identification techniques from
      fMRI data.

PMID- 21097317
TI  - Wideband MRI: theoretical analysis and its applications.
AB  - Wideband MRI, a novel technique that utilized expanded bandwidth with several
      carriers, has been demonstrated to increase the throughput of MR imaging. Various
      MR imaging methods, especially those that require large coverage, have
      successfully take advantage of Wideband MRI and obtain speedup as high as to 8X.
      The fundamental physics of Wideband MRI was inspected from basic equations
      derived in this paper, not only evaluating the pros and cons, but also providing
      guidelines for designs. Two possible Wideband MRI applications are completed in
      this study. One is to accelerate the total scan time of a whole body study, and
      the other to obtain images with finer detailed information without consuming
      excessive time. In either experiment, Wideband MRI proves itself to be a powerful
      tool for the evolution of MR imaging and biomedical imaging as well.

PMID- 21097318
TI  - Brain activation in complex partial seizures during switching from a the goal
      directed task to a resting state: comparison of fMRI maps to the default mode
      network.
AB  - The default mode network (DMN) has been previously identified as a set of brain
      regions activated during internally directed cognition. The objective of this
      study was to investigate patterns of brain activation during switching between a
      goal-directed task and a rest period obtained from clinical functional magnetic
      resonance imaging (fMRI) paradigms in complex partial seizures (CPS) and age
      matched controls. As part of pre-surgical evaluation with fMRI, a visually
      presented block-design language task was performed by eight subjects (4 CPS, 4
      age-matched controls). Single subject fMRI maps were calculated and transferred
      into Talairach space for an atlas-based analysis. For the rest state, total
      volumes of activation, brain regions with largest volume of activation and
      regions commonly activated in the CPS and the control group were identified. A
      voxel-by-voxel comparison was conducted to reveal inter-group statistically
      significant differences. Average volume of activation in the CPS group was
      significantly higher (32,080 mm(3)) than in the control group (7,915 mm(3), p
      value < 0.03). In both groups, most of the common activation volume (81% in the
      CPS group and 98 % in the control group) was located in cognitive regions of the
      frontal lobe and temporal lobes as well as anterior cingulate cortex, precuneus
      and cuneus. The remaining 19% in the CPS group included regions in the precentral
      gyrus, the superior and medial occipital gyrus, the parahippocampal gyrus, the
      inferior parietal lobule and the angular gyrus. The voxel-by-voxel comparison
      showed larger areas of activation mostly in the frontal and temporal lobes in the
      CPS group (as well as in the cuneus and precuneus), while regions with larger
      activation in the control group were found mostly in the parietal lobe. Our
      findings implicate that switching from goal-directed behavior to the default mode
      in CPS patients is impaired. Information contained in clinical fMRI block-design
      image data can be used to quantify this impairment.

PMID- 21097319
TI  - In vivo MRI study of the visual system in normal, developing and injured rodent
      brains.
AB  - This paper demonstrated our recent use of contrast-enhanced MRI, diffusion
      tensor/kurtosis imaging, proton magnetic resonance spectroscopy, and functional
      MRI techniques, for in vivo and global assessments of the structure, metabolism
      and function of the visual system in rodent studies of ocular diseases, optic
      neuropathies, developmental plasticity and neonatal hypoxic-ischemic brain injury
      at 7T. Results suggested the significant values of high-field multiparametric MRI
      for uncovering the processes and mechanisms of developmental and
      pathophysiological changes systematically along both anterior and posterior
      visual pathways, and may provide early diagnoses and therapeutic strategies for
      promoting functional recovery upon partial vision loss.

PMID- 21097320
TI  - A three-coil RF probe-head at 2.35 T: Potential applications to the (23)Na and to
      the hyperpolarized (129)Xe MRI in small animals.
AB  - We present in this paper a dedicated home-built RF probe-head for the MRI of rat
      brain at 2.35 T. This probe consists of an association of three coils: a double
      tuned birdcage coil, which could be used for both transmitting and receiving, and
      a single-tuned surface coil that is used for the only receiving. This single
      tuned coil is actively decoupled from the double-tuned volume coil. The active
      decoupling is based on the pole insertion technique using PIN diodes circuitry.
      This development was initially motivated by its potential and future application
      to the brain perfusion measurements by the MRI of hyperpolarized xenon-129 (HP
      (129)Xe). However, one of underlying ideas behind this work is to proceed well
      beyond this specific application. Particularly, the developed coil could also be
      dedicated for the sodium-23 ((23)Na) MRI in the rat brain. Indeed we tried to
      make the design versatile, simple and easy to replicate by other research groups,
      with a low cost, minimum development time and accepted performances. We believe
      that this design could by useful for groups who consider building own hardware.
      This is why we describe in some details the practical aspects of the workbench
      design as well as the coil characterization. For simplicity reasons, the first
      results of developed prototype were obtained at 100 MHz and 26.4 MHz (proton and
      sodium-23 frequencies at 2.35 T). MR images of phantoms were realized. In-vivo
      (1)H images and (23)Na spectra of the rat brain were also obtained. Future
      validation would concern the MRI of HP (129)Xe.

PMID- 21097321
TI  - Integrated software for the detection of epileptogenic zones in refractory
      epilepsy.
AB  - In this paper we present an integrated software designed to help nuclear medicine
      physicians in the detection of epileptogenic zones (EZ) by means of ictal
      interictal SPECT and MR images. This tool was designed to be flexible, friendly
      and efficient. A novel detection method was included (A-contrario) along with the
      classical detection method (Subtraction analysis). The software's performance was
      evaluated with two separate sets of validation studies: visual interpretation of
      12 patient images by an experimented observer and objective analysis of virtual
      brain phantom experiments by proposed numerical observers. Our results support
      the potential use of the proposed software to help nuclear medicine physicians in
      the detection of EZ in clinical practice.

PMID- 21097322
TI  - Multiple-Model Set-Valued Observers: a new tool for HRF model selection in fMRI.
AB  - This paper proposes a new approach for the selection of a biophysical model
      describing the haemodynamic response function (HRF) measured in BOLD-fMRI data,
      based on model falsification techniques. Specifically, the novel method of
      Multiple Model Set-Valued Observers (MMSVOs) is introduced. The observers
      consider that the initial state lives in a set, the linear time-varying dynamic
      system obtained from a bilinear approximation of the nonlinear HRF model about
      the nominal input signal is uncertain, and the output measurements are corrupted
      by bounded noise. It is shown, both theoretically and through simulation, that
      the proposed method is able to successfully distinguish the correct HRF model
      among a set of physiologically plausible alternatives. Moreover, the feasibility
      of the technique is demonstrated by its application to an empirical dataset. In
      summary, the results obtained clearly indicate that the proposed methodology is
      potentially well-suited to be used in the modeling of BOLD-fMRI data.

PMID- 21097323
TI  - Joint fMRI brain activation detection and segmentation using level sets.
AB  - This paper proposes a parametric, multivariate method for the joint detection and
      segmentation of brain activation based on fMRI data. The proposed technique uses
      region based level sets to separate between the task-related and non-task-related
      regions and performs, at each iteration of level set evolution, a separate
      multivariate linear model (MLM) analysis in each of the two regions. Simulations
      using synthetic data generated based on typical experimental parameters and noise
      levels showed a false positive rate of 6% and a false negative rate of 2% for the
      results obtained with the proposed technique. The performance of the level sets
      method was further investigated by analysing empirical fMRI data from two
      subjects performing a visual and a motor task. Our results indicate that the
      proposed technique provides brain activation results comparable to those obtained
      by a standard univariate approach, with the advantage that it does not require
      the definition of a significance threshold.

PMID- 21097324
TI  - Image resolution improvement based on sinogram super-resolution in PET.
AB  - One of the limits of PET imaging is the low spatial resolution due to a
      predetermined detector width. To overcome this limit, we may increase the number
      of samples by using the wobbling motion. Since the line spread function (LSF) of
      the sinogram is determined by the detector width, however, the increase of the
      number of samples is not sufficient to improve the sinogram resolution. In this
      paper, based on oversampled data obtained from the wobbling motion, we propose a
      novel and efficient super-resolution (SR) scheme for the sinogram. Since the
      proposed SR scheme adopts the penalized expectation maximization (EM) algorithm,
      it guarantees non-negative values of the super-resolved sinogram data. Through
      the experiments, we demonstrate that the proposed SR scheme can noticeably
      improve the spatial image resolution.

PMID- 21097325
TI  - Estimation of coronary length-volume allometric relations of human arteries in
      vivo using CT.
AB  - Assessing the individual geometry of the coronary arteries in a patient can help
      to explain diffuse artery disease. Some allometric functions, relating arterial
      length and volume, were verified in porcine arteries and human autopsies but not
      in vivo. In this work we use skeletonization methods on MSCT images to render the
      whole coronary tree in healthy and cardiovascular patients. Twenty patients with
      and without coronary artery disease were recruited. The coronary was segmented
      with minimum user intervention. Vessels were separated and measured. A 3D
      coronary map was individually calculated. The allometric length-volume function
      L=k(v)V(beta) was evaluated in each patient and plotted in a Log-Log scale. The
      coefficient k(v) ranged 1.00 +/- 0.35. Slopes ranged beta = 0.69-0.88 and seemed
      to overlap in the scatter Log plot. The analysis of covariance verified this
      perception and concluded that lines were parallel. In other words, the allometric
      function stood for all patients. Values were not different from other studies in
      humans and pigs. The combination of multislice CT with morphological extraction
      algorithms was effective to extract allometric functions from coronary arteries
      in patients and can be easily applied in the clinic.

PMID- 21097326
TI  - Analysis of the helix and transverse angles of the muscle fibers in the
      myocardium based on Diffusion Tensor Imaging.
AB  - Realistic models of the muscle fibers in the myocardium improve the understanding
      and simulation of the bio-mechanical behavior of the heart. Since Diffusion
      Tensor Imaging (DTI) allows to visualize the fiber structures in the tissues,
      this modality can be used to build fiber models. In this paper, we propose an
      automatic method for the analysis of the helix and transverse angles between the
      fibers and the myocardial wall. It computes automatically the theoretical value
      of these angles (according to a mathematical model described in the literature)
      at each voxel of the image as well as the real value based on the DTI
      acquisition. In addition, new parameters of the mathematical model can be
      estimated based on our approach to personalize the model for specific data-sets.

PMID- 21097328
TI  - Exploratory data analysis of image texture and statistical features on myocardium
      and infarction areas in cardiac magnetic resonance images.
AB  - The cardiac magnetic resonance (CMR) images from a group of patients with
      myocardial scars and implanted cardioverter-defibrillator (ICD) are divided into
      a group with low risk of arrhythmias (late incidents) and a group with high risk
      of arrhythmias (early incidents). Several hundred quantitative features
      describing sizes, statistics and textures of the segmented and defined areas of
      the images are computed from manually segmented images in an exploratory
      analysis. The method used to determine decision regions to discriminate the
      patients with low risk of arrhythmias from the patient with high risk of
      arrhythmias is a maximum likelihood estimation based Bayes classifiers described
      in [1]. The results presented can be interpreted as hypothesis of which features,
      and combinations of features, that might have discriminative power. A major
      hypothesis that arises is that there are important textural information in the
      scarred and non-scarred areas.

PMID- 21097327
TI  - A qualitative and quantitative study of coronary artery MRA.
AB  - In this paper, we propose an analysis of the coronary arterial tree obtained
      through magnetic resonance angiography (MRA). Ten datasets of the state-of-the
      art SSFP MRI sequence are first qualitatively evaluated and labelled. Second, a
      quantitative analysis of anatomical and image features is performed. Finally, a
      comparison with an existing semi-automatic centreline extraction method is
      reported. The discussion deals with the clinical usage of such an imaging
      modality for both global anatomy visualisation and quantification purpose.

PMID- 21097329
TI  - Factor analysis of ventricular contraction using SPECT-ERNA images.
AB  - Equilibrium radionuclide angiography images (ERNA) has been established as a
      useful modality for clinical evaluation of the ventricular function. Tomographic
      acquisition of ERNA (SPECT-ERNA) improves the quantification of ventricular
      function with planar ERNA, avoiding both the overlap of structures and the need
      of defining the best septal view which can be difficult in dilated ventricles. In
      this work we analyze the contribution and distribution of the most significant
      factors of dynamic structures (FADS), and propose an index based on the
      characterization of the normal contraction pattern, to quantify the ventricular
      contraction normality in a set of patients with clinical diagnosis of pulmonary
      arterial hypertension (PAH) using SPECT-ERNA. The statistical analysis shows
      significant differences between normal and PAH subjects in the models of left
      ventricle (LV) contraction pattern. This comparison shows that the LV has an
      abnormal contraction as a consequence of the pulmonary arterial hypertension.

PMID- 21097330
TI  - Portable nanoparticle quantization using a resizable nanopore instrument - the
      IZON qNanoTM.
AB  - This paper demonstrates initial results with a novel instrument for nanoparticle
      detection and quantization, called the "qNano." The qNano instrument provides a
      label-free method for detection of charged particles passing through a nanopore
      (a nanopore scale channel that separates two volumes) via electrophoresis. The
      instrument incorporates an elastomeric membrane in which a nano-scale pore has
      been produced by mechanical puncturing, and stretching of the membrane allows
      control of the nanopore size. Trans-membrane voltage drives electrophoresis and
      particle translocations through the nanopore, as measured by the ionic current
      that flows through the pore. Pressure control is also available to increase the
      rates of capture and translocation. We demonstrate quantization of liposome and
      polystyrene particles ranging from 200-400 nm. Capture rate (translocation events
      per second) is shown to be linear with respect to applied pressure and membrane
      stretching distance. Additionally, translocation event amplitude is shown to
      decrease with increasing pressure, but remains invariant to changes in the
      membrane stretching distance.

PMID- 21097331
TI  - AC Biosusceptometry as a method for measuring gastric contraction.
AB  - The aim of this study was to validate the alternate current biosusceptometry
      (ACB) for monitoring gastric contractions in rats. In vitro data were obtained to
      establish the relationship between ACB and the strain-gauge (SG) signal
      amplitude. In vivo experiments were performed on rats with magnetic markers and
      SGs previously implanted under the gastric serosa. The effects of the prandial
      state in gastric motility profiles were obtained. The correlation between in
      vitro signal amplitudes was strong (R = 0.989). The temporal cross-correlation
      between the ACB and SG signal amplitude was higher in the postprandial than in
      the fasting state. Irregular signal profiles, low contraction amplitudes, and
      smaller signal-to-noise ratios explained the poor correlation for fasting-state
      recordings. The contraction frequencies using ACB were 0.068 +/- 0.007 Hz
      (postprandial) and 0.058 +/- 0.007 Hz (fasting) and those using SG were 0.066 +/-
      0.006 Hz (postprandial) and 0.059 +/- 0.008 Hz (fasting) (P < 0.003). When a
      magnetic tracer was ingested, there was a strong correlation and a small phase
      difference between techniques. We conclude that ACB provides an accurate and
      sensitive technique for studies of GI motility in the rat.

PMID- 21097332
TI  - Effect of pressurization methods on the accuracy of wrist blood pressure
      measurement.
AB  - In developing a wrist blood pressure monitor of high and reliable accuracy, the
      effect of different pressurization methods on the accuracy of blood pressure
      measurement at the wrist using oscillometry is investigated in this paper. 30
      volunteers are recruited and blood pressure readings are taken with three
      different methods of pressurizing the wrist. It was found that measurement of
      mean arterial pressure (MAP) is more accurate when the wrist is locally
      compressed directly over the radial artery (-2.6 +/- 11.4 mmHg) or with a region
      of surrounding tissue (10.3 +/- 6.0 mmHg) than when the whole wrist is compressed
      by a conventional, constricting cuff (-11.4 +/- 16.4 mmHg). Characteristics of
      accuracy, however, differ between the two local pressurization methods. While a
      square airbag that compresses the wrist directly over the radial artery may
      measure the most accurate MAP on average, the range of errors among individuals
      is large. Contrarily, measurements taken by pressurizing a region over the radial
      artery with a bladder are least affected by individual variability. In order to
      measure blood pressure accurately at the wrist while unbiased by the population
      based algorithmic compensation to ensure accuracy among different individuals,
      therefore, the use of local pressurization method may be the most appropriate.

PMID- 21097333
TI  - Insole with pressure control and tissue neoformation induction systems for
      diabetic foot.
AB  - This article presents the development of a prototype insole derived from natural
      rubber from Hevea brasiliensis, equipped with pressure control and capable of
      neoformation of tissue for people who have diabetic foot. The active element of
      this insole is the electronic circuit that monitors the plantar pressure. In
      addition, on the present stage of the research, a signal irradiating cell is used
      based on the principle of tissue regeneration using laser. This project proposes
      a "smart" insole prototype with a pressure monitoring system and an electronic
      system for tissue regeneration, which will open a new approach in an attempt to
      solve the problem of diabetic foot.

PMID- 21097334
TI  - Electronic system for monitoring the frequency and pressure of mastication: study
      and approach for its design.
AB  - The objective of this work is to study and design a portable non invasive
      prototype which allows us to supervise the mastication frequency and pressure for
      specific meals, performing an analysis of sounds and pressures generated by
      facial muscles when they are chewing. These variables have a direct influence on
      people nutritious and dietary habits; also, a quickly eating makes people ingest
      a lot of food instead he needs generating overweight on him. On the other hand,
      there is no so much study for upheaval of temporal-mandible joints (TMJ) in Peru,
      keeping as reference that unilateral mastication is one of the principal causes
      on myofacial pains but, as obesity, there are no studies in Peru about how to
      prevent these pathologies. In consequence, we propose the development of this
      prototype which, additional to supervise variables such as mastication frequency
      and pressure, will allow to the patient an self-correction of his habits.

PMID- 21097335
TI  - Ultrasound user-identification for wireless sensor networks.
AB  - Indoor localization and asset tracking is an area of research which is finding
      increasing application in monitoring the wellbeing of elderly subjects in
      hospital or residential care environments. Radio frequency (RF) based
      localization methods tend to show poor performance in indoor environments, due to
      multipath scatter, and simple room-level misassociations, resulting from the
      relative transparency of some walls to RF waves. Ultrasound (US) localization has
      shown excellent room-level accuracy, and as US will not easily penetrate walls,
      room-level misassociations do not often occur. For normal asset tracking systems,
      the association between an asset and a room is not of critical importance; for
      clinical applications, which make inferences based on a patient and carer
      occupying the same room, this association is paramount. This paper outlines a
      proof of concept for an US-based indoor localization system with sub-room-level
      accuracy. The proposed design uses a US-based technique, with transmitter beacons
      placed throughout the environment. The subject wears the receiver module and is
      free to move throughout the environment. Transmission collisions are alleviated
      by assigning a unique prime transmission interval to each beacon; meaning the
      beacons do not require synchronization or coordination and operate independently
      of one another. Preliminary results show accurate detection at a range of over 5
      m at a 0 degrees  angle and at approximately 3.5 m at an angle of 30 degrees .
      Testing of two collocated transmitters, transmitting in the same plane and
      separated by 2.5 m results in accurate reception of both signals, even within the
      region of overlap.

PMID- 21097336
TI  - Experimental validation of a polyvinylidene fluoride sensing element in a tactile
      sensor.
AB  - A tactile sensor for robotic applications is described, inspired by the
      mechanoreceptors in the glabrous skin of the human hand, in order to replicate
      the sensory function of both slow adapting and fast adapting mechanoreceptors.
      Strain gauges were used for the slow adapting receptors, and polyvinylidene
      fluoride (PVDF) film was used to replicate the fast adapting receptors. A finite
      element analysis (FEA) model was used to predict the output response of the PVDF
      film, and verified experimentally. The PVDF film was observed to respond linearly
      to mechanical stress and exhibited increased gain at higher frequencies. "Ramp
      and hold" stimuli were applied to the tactile unit sensor, and the PVDF film only
      responded at contact onset and offset, similar to the response of fast adapting
      receptors. The PVDF acted as a dynamic sensing element for the proposed tactile
      sensor unit.

PMID- 21097337
TI  - Point-type non-contact stiffness sensing of soft tissue with coupling effect.
AB  - This paper discusses the point-type non-contact active sensing for evaluating the
      stiffness of a soft tissue with coupling effect. Tfhe sensing system imparts a
      point force to a tissue and measures the displacement at the point of application
      of force. The benefit is that such point based information enables us to estimate
      two stiffness parameters constructing the 3D spring network tissue model. Through
      the experiment for a human skin, we show that the deformation shapes between
      human skin surface and the model with the estimated parameters are nicely
      coincident.

PMID- 21097338
TI  - Opto-electronic system for detection of flat foot by using estimation techniques:
      study and approach of design.
AB  - Distribution of Foot Pressure reflects the deformations of body biomechanical
      design. They are caused by different reasons: degenerative, by trauma, etc.,
      being flat foots a common pathology in Peru with high incidence. However there
      isn't the properly technology to detect properly this disease because is detected
      by a non-reliable visual way using pedoscopes. Flat foot is the degree of
      internal plantar arch lack and is well observed in foot pressure distribution.
      This distribution can be obtained by optical or electronic systems. The most
      required, by their accuracy, are the electronic ones but sensor manufacturing
      process increases its price, meanwhile optics provides an indirect optical
      solution whose price depends on scanners resolution. Therefore, this paper takes
      advantage of both systems: a direct pressure value from electronics and no
      problems calibration from optical systems. In regard of these reasons, prototype
      will use a webcam and twelve FSR (Force sensing resistor) sensors including
      estimation techniques, and thus obtain the foot pressure distribution.
      Accordingly, the present study is looking for providing to the specialist with an
      efficient tool to generate better diagnostics in Peru.

PMID- 21097339
TI  - Test system for clinical force platforms.
AB  - Our team has built a system for testing and calibration of clinical Force
      Platforms, able to generate a circular path Center of Pressure (CoP) that can be
      accurately applied in the horizontal plane at a given travel speed, selectable
      radius and vertical force. The CoP generated, which is applied directly onto the
      platform, is used as a precise reference for both static and dynamic
      measurements, to check the operation of unknown Force Platforms performance
      characteristics or to verify specifications indicated by the Force Platform's
      manufacturer. To confirm the feasibility and effectiveness of the proposed test
      apparatus, it was applied to a commercial clinical usage Force Platform
      manufactured by artOficio LTDA. The main advantages of the proposed Test System
      are the accuracy in fixing or setting a direct reference and the ability to
      maintain continuous monitoring through the generation of flexible and stable
      circular patterns during the tests.

PMID- 21097340
TI  - A study of opto-physiological modeling to quantify tissue absorbance in imaging
      photoplethysmography.
AB  - This paper presents an opto-physiological model (OPM) to quantify the absorbance
      of multi-layered tissue in imaging photoplethysmography (IPPG). The approach used
      to generate such a model is to revise the path length of the Beer Lambert law
      through the Monte Carlo (MC) simulation of multi-layered tissue. The OPM can
      mathematically quantify the effect of optical properties on the absorbance of
      multilayered tissue. Subsequently, the absorbance measured from homogeneous,
      multi-layered tissue phantoms compares with model predictions. To this end, the
      model is validated to predict the widest range of experimental outcomes while
      maintaining the highest possible level of accuracy. This study brings a new
      approach to understand the principle of IPPG.

PMID- 21097341
TI  - New ear sensor for mobile, continuous and long term pulse oximetry.
AB  - Pulse oximetry is a valuable monitoring technology used at present mainly for
      immobile patients. The reason for the limitation concerning the user's mobility
      is due principally to unsuitable sensors and sensor locations. This is
      particularly the case with finger sensors, which tend to work best in respect to
      signal quality i.e. modulation depth, but are quite susceptible to motion
      artifacts. In order to achieve mobility for pulse oximetry monitoring, an ear
      canal sensor was developed. This area was chosen based on the assumption that
      intensive movement and acceleration of this part of the body is generally avoided
      as it produces unpleasant feelings.

PMID- 21097342
TI  - Time-resolved diffuse reflectance measurement carried out on the head of an adult
      at large source-detector separation.
AB  - Multichannel time-resolved optical monitoring system was constructed for
      measurements of diffuse reflectance in optically turbid medium at very large
      source-detector separation up to 9 cm. The system is based on femtosecond TiSa
      laser and sensitive photomultiplier tube detector. The laser light of 300mW of
      power was delivered to the surface of the head with the use of an optical fiber.
      A beam expander was applied in order to distribute the laser light on a large
      spot which allowed to avoid energetic stimulation of the tissue. The
      photomultiplier tube detector was positioned directly on the surface of the
      medium at the distance of 9cm from the center of the source position. In this
      paper we report results of an in-vivo experiment carried out on the head of an
      adult healthy volunteer. The time-resolved system was applied during intravenous
      injection of an optical contrast agent (indocyanine green - ICG) and the
      distributions of times of flight of photons were successfully acquired showing
      inflow and washout of the dye to the tissue. Time-courses of the moments of
      distributions of times of flight of photons are presented and compared with the
      results obtained simultaneously at shorter source-detector separations (3 cm, 4
      cm and 5 cm).

PMID- 21097343
TI  - Design of a 3D surface scanner prototype suitable for MR.
AB  - The detection of body movements during MR examination could help in reducing
      motion artifacts or to get patient responses during functional magnetic
      resonance. It can be supported by a slit scanner, that combines a camera with a
      light stripe projector to obtain 3D coordinates of points forming the external
      surface of the body. In this work we propose a slit scanner prototype based on a
      miniaturized projector without moving parts. Just small sized hardware is
      required to analyze the video signal, operating in time domain instead of spatial
      domain. To accomplish this, the camera is placed with its pixel columns as more
      parallel as possible to the projected light stripes and the camera video signal
      is analyzed by a resistor transistor logic after analog processing.

PMID- 21097344
TI  - NURBS for the geometrical modeling of a new family of Compact-Supported Radial
      Basis Functions for elastic registration of medical images.
AB  - In this paper we propose a novel approach to design a family of Radial Basis
      Functions with Compact Support applied to elastic registration of medical images.
      The proposed method is based on Non-Uniform Rational B-Spline theory, which
      introduce a number of practical properties. The proposed method allows to design
      almost perfect equally distributed functions which fulfill most of the
      requirements identified in the recent literature. The Radial Basis Function is
      merely parametrized by the symmetric desired curvature at peak-and-tails.
      Properties of the function are numerically compared with foregoing RBFs.
      Preliminary experimental results indicate its suitability and benefits in
      registration of medical images.

PMID- 21097345
TI  - Science and technology of biocompatible thin films for implantable biomedical
      devices.
AB  - This presentation focuses on reviewing research to develop two critical
      biocompatible film technologies to enable implantable biomedical devices, namely:
      1) development of bioinert/biocompatible coatings for encapsulation of Si chips
      implantable in the human body (e.g., retinal prosthesis implantable in the human
      eye)-the coating involves a novel ultrananocrystalline diamond (UNCD) film or
      hybrid biocompatible oxide/UNCD layered films; and 2) development of
      biocompatible films with high-dielectric constant and microfabrication process to
      produce energy storage super-capacitors embedded in the microchip to achieve full
      miniaturization for implantation into the human bodynovel Al2O3/TiO2
      nanolaminates exhibit abnormally high dielectric constant to enable super
      capacitors with very high-capacitance.

PMID- 21097346
TI  - Spatial characterization of electric potentials generated by pulsed
      microelectrode arrays.
AB  - This presentation is a report on the in situ characterization of stimulating
      microelectrodes in the context of multielectrode retinal prosthetic implants. The
      experimental system approximately replicates the geometric and electrical
      parameters of Second Sight Medical Products' Argus II Retinal Implant.
      Topographic maps of electric potentials have been prepared for a 60 electrode
      structure in which selected electrodes were stimulated with biphasic repetitively
      pulsed charge densities at 100 microC.cm(-2). Surface contour maps were prepared
      using a 10 microm diameter recording electrode.

PMID- 21097347
TI  - Signal processing for a vestibular neurostimulator.
AB  - An implanted vestibular neurostimulator has been developed based on commercial
      cochlear implant technology. It has been implanted chronically in Rhesus monkeys
      and the physiology of electrical stimulation of the vestibular periphery has been
      studied. We are currently proposing a human feasibility study of implantation of
      the device for the treatment of incapacitating Meniere's disease. Because no
      animal model of Meniere's disease exists, signal processing for such a device
      must be based on prior observations of human subjects who have suffered Meniere's
      attacks while their eye-movements could be quantified. Based on such data, and on
      the leading theories for the pathophysiology of a Meniere's attack, our animal
      data suggests that fixed amplitude, constant frequency biphasic pulse trains
      should be adequate to suppress the symptoms of an attack when they occur. The
      intensity of the stimuli and efficacy of vertigo suppression should be readily
      modulated either by amplitude or frequency adjustments.

PMID- 21097348
TI  - The role of biomedical engineering in health system improvement and nation's
      development.
AB  - Biomedical Engineering (BME) undergraduate programs are incipient in Brazil and
      in other South American countries. Accreditation concerns and the Health system
      modernization make necessary for countries such as Brazil to plan the education
      and investments strategy for the next 15 years. BME curricula are not well
      defined in Brazil and this study intends to present the minimum needs. The
      importance of implantation of new BME programs in Brazil and other Latin American
      countries is also discussed.

PMID- 21097349
TI  - The telemetric and Holter ECG warehouse initiative (THEW): a data repository for
      the design, implementation and validation of ECG-related technologies.
AB  - we present an initiative supported by the National Heart Lung, and Blood
      Institute and the Food and Drug Administration for the development of a
      repository containing continuous electrocardiographic information to be shared
      with the worldwide scientific community. We believe that sharing data reinforces
      open scientific inquiry. It encourages diversity of analysis and opinion while
      promoting new research and facilitating the education of new researchers.

PMID- 21097350
TI  - The concept for integration of thermal imaging systems with personal protective
      equipment.
AB  - Work in difficult conditions resulting from limited visibility in conjunction
      with restricted movement and complexity of performed operations involves high
      risk. The hazard can be reduced significantly through rapid provision of
      information on the risks people are exposed to under certain working conditions.
      Their reactions - classified as improper - result most often under stress, in
      particular when acting in limited visibility conditions. This article shall treat
      of reduced visibility understood as lack of visibility resulting from dim light,
      as opposed to the problem of obstructed view, which is not discussed here.

PMID- 21097351
TI  - UV protective textile clothing for workers exposed to natural and artificial UV
      radiation.
AB  - Some amounts of ultraviolet radiation are beneficial for humans but excessive
      exposure can cause many negative health effects to the skin and eyes and also can
      affect the immune system. Exposed area of skin should be covered by working
      clothes with low UVR transmission. It concerns both exposure to natural UV or
      prolonged exposure to artificial UV. This article presents some aspects of UV
      protective textile clothing for workers exposed to natural and artificial UV
      radiation. This article presents results of selected textile samples
      transmittances and calculated UPF and new proposed AUPF, which describes
      protective properties against UV of textiles. The UPF and AUPF differs
      substantially between each other, what is related both to the weighting factors
      of erythema and actinic efficiency functions and spectral range of these
      functions. UV protection by clothing depends on a large variety of factors, such
      as type of fiber, color or moisture content. Contrary to popular opinion,
      however, some fabrics provide insufficient ultraviolet (UV) protection.

PMID- 21097352
TI  - Integration of model-based weighting into an ICP variant to account for
      measurement errors in intra-operative A-Mode ultrasound-based registration.
AB  - This paper addresses error modeling in A-Mode ultrasound- (US-) based
      registration and integration of model-based weighting into the Random-ICP (R-ICP)
      algorithm. The R-ICP is a variant of the Iterative Closest Point (ICP) algorithm,
      and it was suggested for surface-based registration using A-Mode US in the
      context of skull surgery. In that application area the R-ICP could yield high
      accuracy even in case of a small number of data points and a very inaccurate user
      interactive pre-registration. However, it cannot cope with unequal point
      uncertainty, which is an important drawback in the context of hip surgery:
      Uncertainty about the average speed of sound is an error source, whose impact on
      the registration accuracy increases with the thickness of the scanned soft
      tissue. It can, therefore, lead to considerable localization errors if a thick
      soft tissue layer is scanned, and it might vary a lot from data point to data
      point as the soft tissue thickness is inhomogeneous. The present work
      investigates how to account for this error source considering also other error
      sources such as the establishment of point correspondences. Simulation results
      show that registration accuracy can be substantially improved when model-based
      weighting is integrated into the R-ICP.

PMID- 21097353
TI  - A computationally efficient approach for 2D-3D image registration.
AB  - 2D-3D image registration has become an important tool in many clinical
      applications such as image-guided surgery and the kinematic analysis of bones in
      knee and ankle joints. A limitation of this approach is the need to recalculate
      the voxel values in the 3D volume for every iteration of the registration
      procedure. In this paper we propose a new 2D-3D image registration algorithm
      which uses the projected 2D data from the original 3D CT volume. For the majority
      of the iterations of the algorithm, only this 2D data is updated rather than the
      3D volume. Experimental results show that similar registration accuracy to the
      approach which employs 3-D updates at every iteration can be achieved with our
      method if we employ 3-D updates only in the last few iterations. As a result of
      reducing the number of 3-D updates, the proposed approach reduces the time
      required to perform the registration by approximately a factor of five.

PMID- 21097354
TI  - Temporal registration for low-quality retinal images of the murine eye.
AB  - This paper presents an investigation into different approaches for segmentation
      driven retinal image registration. This constitutes an intermediate step towards
      detecting changes occurring in the topography of blood vessels, which are caused
      by disease progression. A temporal dataset of retinal images was collected from
      small animals (i.e. mice). The perceived low quality of the dataset employed
      favoured the implementation of a simple registration approach that can cope with
      rotation, translation and scaling, in the presence of major vascular
      dissimilarities, distortions, noise, and blurring effects. The proposed approach
      uses a single control point, i.e. the centroid of the optic disc, and achieves
      accurate registration by matching points in the pair of input images using mean
      squared error calculation. A number of alternative, more sophisticated methods
      have been explored alongside the proposed one. While these other methods could
      prove valuable and perform reasonably well when applied on good quality images,
      they generally fail when using the dataset at hand.

PMID- 21097355
TI  - Medical image registration using TSallis Entropy in Statistical Parametric
      Mapping (SPM).
AB  - The superposition of medical images, technically known as co-registration, can
      take a major role in determining the topographic and morphological changes in
      functional diagnostic and therapeutic purposes. This paper describes a study
      focused on to find an alternative cost function method for medical images co
      registration through the study of performance and robustness of the TSallis
      Entropy in Statistical Parametric Mapping package (SPM). Images of Magnetic
      Resonance (MR) and Single Photon Emission Computed Tomography (SPECT) of 3
      patients morphologically normal were used for the construction of anatomic
      phantoms containing predetermined geometric variations. The simulated images were
      co-registered with the original images using traditional techniques and the
      proposed method. The comparative analysis of the Root Mean Square (RMS) error
      showed that the Tsallis Entropy was more efficient in the intramodality
      alignment, while the Shannon Entropy in the intermodality one; revealing
      therefore the importance of the implementation of the Tsallis Entropy in SPM for
      applications in neurology and neuropsychiatric evaluation.

PMID- 21097356
TI  - An integrated software solution for multi-modal mapping of morphological and
      functional ocular data.
AB  - Various morphological and functional techniques for retina examination have been
      established in the recent years. Although many examination results are spatially
      resolved and can be mapped onto data originating from other modalities, usually
      only data from one modality is analyzed by a clinician at a time. This is mainly
      because there is no software available to the public that enables the
      registration of structure and function in the clinical setting. Therefore we
      developed an integrated mapping application that allows the registration and
      analysis of morphological data (fundus photography, optical coherence tomography,
      scanning laser ophthalmoscopy images, and GDx thickness profiles) and functional
      data (multifocal electroretinography, multifocal pattern electroretinography,
      perimetry, and microperimetry). To obtain quantitative data that can be used for
      clinical trials and statistical analyses, extraction routines for morphological
      parameters - such as retinal layer thicknesses and measures of the vascular
      network - have been integrated. Global, regional and point-specific data from
      registered modalities can be extracted and exported for statistical analyses. In
      this article we present the implementation and examples of use of the developed
      software.

PMID- 21097357
TI  - Validation through accuracy prediction in neuroimage registration.
AB  - Validation and accuracy assessment are the main bottlenecks preventing the
      adoption of many medical image processing algorithms in the clinical practice. In
      the classical approach, a-posteriori analysis is performed based on some
      predefined objective metrics. The main limitation of this methodology is in the
      fact that it does not provide a mean to estimate what the performance would be a
      priori, and thus to shape the processing workflow in the most suitable way. In
      this paper, we propose a different approach based on Petri Nets. The basic idea
      consists in predicting the accuracy that will result from a given processing on a
      given type of data based on the identification and characterization of the
      sources of inaccuracy intervening along the whole chain. Here we propose a proof
      of concept in the specific case of image registration. A Petri Net is constructed
      after the detection of the possible sources of inaccuracy and the evaluation of
      their respective impact on the estimation of the deformation field. A training
      set of five different synthetic volumes is used. Afterward, validation is
      performed on a different set of five synthetic volumes by comparing the estimated
      inaccuracy with the posterior measurements according to a set of predefined
      metrics. Two real cases are also considered. Results show that the proposed model
      provides a good prediction performance. An extended set of clinical data will
      allow the complete characterization of the system for the considered task.

PMID- 21097358
TI  - A comparison of the 3D kinematic measurements obtained by single-plane 2D-3D
      image registration and RSA.
AB  - 3D computed tomography (CT) to single-plane 2D fluoroscopy registration is an
      emerging technology for many clinical applications such as kinematic analysis of
      human joints and image-guided surgery. However, previous registration approaches
      have suffered from the inaccuracy of determining precise motion parameters for
      out-of-plane movements. In this paper we compare kinematic measurements obtained
      by a new 2D-3D registration algorithm with measurements provided by the gold
      standard Roentgen Stereo Analysis (RSA). In particular, we are interested in the
      out-of-plane translation and rotations which are difficult to measure precisely
      using a single plane approach. Our experimental results show that the standard
      deviation of the error for out-of-plane translation is 0.42 mm which compares
      favourably to RSA. It is also evident that our approach produces very similar
      flexion/extension, abduction/adduction and external knee rotation angles when
      compared to RSA.

PMID- 21097359
TI  - Performance of Combined Support Vector Machine and Principal Component Analysis
      in recognizing infant cry with asphyxia.
AB  - Combined Support Vector Machine (SVM) and Principal Component Analysis (PCA) was
      used to recognize the infant cries with asphyxia. SVM classifier based on
      features selected by the PCA was trained to differentiate between pathological
      and healthy cries. The PCA was applied to reduce dimensionality of the vectors
      that serve as inputs to the SVM. The performance of the SVM utilizing linear and
      RBF kernel was examined. Experimental results showed that SVM with RBF kernel
      yields good performance. The classification accuracy in classifying infant cry
      with asphyxia using the SVM-PCA is 95.86%.

PMID- 21097360
TI  - Analysis of spontaneous MEG activity in mild cognitive impairment using spectral
      entropies and disequilibrium measures.
AB  - The aim of this study was to explore the ability of several spectral entropies
      and disequilibrium measures to discriminate between spontaneous
      magnetoencephalographic (MEG) oscillations from 18 mild cognitive impairment
      (MCI) patients and 24 controls. The Shannon spectral entropy (SSE), Tsallis
      spectral entropy (TSE), and Renyi spectral entropy (RSE) were calculated from the
      normalized power spectral density to evaluate the irregularity patterns. In
      addition, the Euclidean (ED) and Wootters (WD) distances were computed as
      disequilibrium measures. Results revealed statistically significant lower SSE and
      TSE(2) values for MCI patients than for controls (p < 0.05) in the right lateral
      region of the brain. ED also obtained statistically significant lower values for
      MCI patients than for controls using the (p < 0.05) in the right lateral region
      of the brain. These findings suggest that MCI is associated with a significant
      decrease in irregularity of MEG activity. In addition, the highest accuracy of
      64.3% was achieved by the SSE. We conclude that measures from information theory
      can be useful to both characterize abnormal brain dynamics and help in MCI
      detection.

PMID- 21097361
TI  - Doppler based identification of uterine artery and umbilical artery for
      monitoring pregnancy.
AB  - In this paper, we present an algorithm to identify umbilical and uterine arteries
      from a set of four different maternal and fetal arteries using their Doppler
      signatures. To distinguish these arteries, we use 132 Doppler signals collected
      from pregnant women with gestational ages between 24 to 40 weeks. Initially we
      filter them to remove noise; spectrograms are generated to extract good cycles,
      which are then analyzed to derive independent features that could uniquely
      represent an artery. A non-linear classification technique using k-NN (k-nearest
      neighbor) classifier is further applied to identify umbilical and uterine
      arteries. The proposed algorithm achieves sensitivity and specificity of above
      95% and 97% for identification of uterine artery and above 63% and 80% for
      umbilical artery.

PMID- 21097362
TI  - Diversity-based selection of components for fusion classifiers.
AB  - Fusion classifiers with diverse components (classifiers or data sets) outperform
      those with less diverse components. Determining component diversity, therefore,
      is of the utmost importance in the design of fusion classifiers which are often
      employed in clinical diagnostic and numerous other pattern recognition problems.
      In this paper, a new pairwise diversity-based ranking strategy is introduced to
      select a subset of ensemble components, which when combined, will be more diverse
      than any other component subset of the same size. The strategy is unified in the
      sense that the components can be either polychotomous classifiers or
      polychotomous data sets. Classifier fusion and data fusion systems are formulated
      based on the diversity selection strategy and the application of the two fusion
      strategies are demonstrated through the classification of multi-channel event
      related potentials (ERPs). From the results it is concluded that data fusion
      outperforms classifier fusion. It is also shown that the diversity-based data
      fusion system outperforms the system using randomly selected data components.
      Furthermore, it is demonstrated that the combination of data components that
      yield the best performance, in a relative sense, can be determined through the
      diversity selection strategy.

PMID- 21097363
TI  - Performance of dynamic features in classifying scalp epileptic interictal and
      normal EEG.
AB  - Over 50 million people worldwide suffer from epilepsy. Recently, researchers have
      proposed computer-aided epilepsy diagnostic systems based on classifying scalp
      epileptic interictal and normal EEG. Features used in the classification can be
      divided into two groups: classical spectral features and dynamic features.
      Classical spectral features are similar to major frequency component
      identification that physicians use in conventional EEG reading. Because dynamic
      features are new compared to classical spectral features, we are interested in
      knowing whether they are suitable for this classification problem. To study this,
      we build such a system and compare the results between using classical spectral
      features and dynamic features. Furthermore, we study which dynamic features are
      more suitable, i.e., more discriminative, by ranking them using F-score.
      According to the result, we discuss redesigning certain dynamic features for
      better classification. This research is a preliminary study of using dynamic
      features of scalp interictal EEG for epilepsy diagnosis.

PMID- 21097364
TI  - Acoustics based assessment of respiratory diseases using GMM classification.
AB  - The focus of this paper is to present a method utilizing lung sounds for a
      quantitative assessment of patient health as it relates to respiratory disorders.
      In order to accomplish this, applicable traditional techniques within the speech
      processing domain were utilized to evaluate lung sounds obtained with a digital
      stethoscope. Traditional methods utilized in the evaluation of asthma involve
      auscultation and spirometry, but utilization of more sensitive electronic
      stethoscopes, which are currently available, and application of quantitative
      signal analysis methods offer opportunities of improved diagnosis. In particular
      we propose an acoustic evaluation methodology based on the Gaussian Mixed Models
      (GMM) which should assist in broader analysis, identification, and diagnosis of
      asthma based on the frequency domain analysis of wheezing and crackles.

PMID- 21097366
TI  - Perspectives on clinical engineering around the world.

PMID- 21097367
TI  - Between people and machines.

PMID- 21097368
TI  - Scopes too flexible...and too stiff.

PMID- 21097369
TI  - Science meets business.

PMID- 21097370
TI  - Quality of life on trial.

PMID- 21097371
TI  - Vital signs: heart rate.

PMID- 21097372
TI  - B-scan based acoustic source reconstruction for magnetoacoustic tomography with
      magnetic induction (MAT-MI).
AB  - We present in this study, an acoustic source reconstruction method using focused
      transducer with B-mode imaging for magnetoacoustic tomography with magnetic
      induction (MAT-MI). MAT-MI is an imaging modality proposed for noninvasive
      conductivity imaging with high spatial resolution. In MAT-MI, acoustic sources
      are generated in a conductive object by placing it in a static and a time-varying
      magnetic field. The acoustic waves from these sources propagate in all directions
      and are collected with transducers placed around the object. The collected signal
      is then used to reconstruct the acoustic source distribution and to further
      estimate the electrical conductivity distribution of the object. A flat piston
      transducer acting as a point receiver has been used in earlier MAT-MI systems to
      collect acoustic signals. In this study, we propose to use B-mode scan scheme
      with a focused transducer that gives a signal gain in its focus region and
      improves the MAT-MI signal quality. A simulation protocol that can take into
      account different transducer designs and scan schemes for MAT-MI imaging is
      developed and used in our evaluation of different MAT-MI system designs. It is
      shown in our computer simulations that as compared to the earlier approach, the
      MAT-MI system using B-scan with a focused transducer allows MAT-MI imaging at a
      closer distance and has improved system sensitivity. In addition, the B-scan
      imaging technique allows reconstruction of the MAT-MI acoustic sources with a
      discrete number of scanning locations, which greatly increases the applicability
      of the MAT-MI approach, especially when a continuous acoustic window is not
      available in real clinical applications. We have also conducted phantom
      experiments to evaluate the proposed method, and the reconstructed image shows a
      good agreement with the target phantom.

PMID- 21097373
TI  - Adaptively learning local shape statistics for prostate segmentation in
      ultrasound.
AB  - Automatic segmentation of the prostate from 2-D transrectal ultrasound (TRUS) is
      a highly desired tool in many clinical applications. However, it is a very
      challenging task, especially for segmenting the base and apex of the prostate due
      to the large shape variations in those areas compared to the midgland, which
      leads many existing segmentation methods to fail. To address the problem, this
      paper presents a novel TRUS video segmentation algorithm using both global
      population-based and patient-specific local shape statistics as shape constraint.
      By adaptively learning shape statistics in a local neighborhood during the
      segmentation process, the algorithm can effectively capture the patient-specific
      shape statistics and quickly adapt to the local shape changes in the base and
      apex areas. The learned shape statistics is then used as the shape constraint in
      a deformable model for TRUS video segmentation. The proposed method can robustly
      segment the entire gland of the prostate with significantly improved performance
      in the base and apex regions, compared to other previously reported methods. Our
      method was evaluated using 19 video sequences obtained from different patients
      and the average mean absolute distance error was 1.65 +/- 0.47 mm.

PMID- 21097374
TI  - Fully automated reduction of ocular artifacts in high-dimensional neural data.
AB  - The reduction of artifacts in neural data is a key element in improving analysis
      of brain recordings and the development of effective brain-computer interfaces.
      This complex problem becomes even more difficult as the number of channels in the
      neural recording is increased. Here, new techniques based on wavelet thresholding
      and independent component analysis (ICA) are developed for use in high
      dimensional neural data. The wavelet technique uses a discrete wavelet transform
      with a Haar basis function to localize artifacts in both time and frequency
      before removing them with thresholding. Wavelet decomposition level is
      automatically selected based on the smoothness of artifactual wavelet
      approximation coefficients. The ICA method separates the signal into independent
      components, detects artifactual components by measuring the offset between the
      mean and median of each component, and then removing the correct number of
      components based on the aforementioned offset and the power of the reconstructed
      signal. A quantitative method for evaluating these techniques is also presented.
      Through this evaluation, the novel adaptation of wavelet thresholding is shown to
      produce superior reduction of ocular artifacts when compared to regression,
      principal component analysis, and ICA.

PMID- 21097375
TI  - Noninvasive intracranial pressure assessment based on a data-mining approach
      using a nonlinear mapping function.
AB  - The current gold standard to determine intracranial pressure (ICP) involves an
      invasive procedure for direct access to the intracranial compartment. The risks
      associated with this invasive procedure include intracerebral hemorrhage,
      infection, and discomfort. We previously proposed an innovative data-mining
      framework of noninvasive ICP (NICP) assessment. The performance of the proposed
      framework relies on designing a good mapping function. We attempt to achieve
      performance gain by adopting various linear and nonlinear mapping functions. Our
      results demonstrate that a nonlinear mapping function based on the kernel
      spectral regression technique significantly improves the performance of the
      proposed data-mining framework for NICP assessment in comparison to other linear
      mapping functions.

PMID- 21097377
TI  - MRF-based intensity invariant elastic registration of cardiac perfusion images
      using saliency information.
AB  - In this paper, we propose a Markov random field-based method that uses saliency
      and gradient information for elastic registration of dynamic contrast enhanced
      (DCE) magnetic resonance (MR) images of the heart. DCE-MR images are
      characterized by rapid intensity changes over time, thus posing challenges for
      conventional intensity-based registration methods. Saliency information
      contributes to a contrast invariant metric to identify similar regions in spite
      of contrast enhancement. Its robustness and accuracy are attributed to a close
      adherence to a neurobiological model of the human visual system (HVS). The HVS
      has a remarkable ability to match images in the face of intensity changes and
      noise. This ability motivated us to explore the efficacy of such a model for
      registering DCE-MR images. The data penalty is a combination of saliency and
      gradient information. The smoothness cost depends upon the relative displacement
      and saliency difference of neighboring pixels. Saliency is also used in a
      modified narrow band graph cut framework to identify relevant pixels for
      registration, thus reducing the number of graph nodes and computation time.
      Experimental results on real patient images demonstrate superior registration
      accuracy for a combination of saliency and gradient information over other
      similarity metrics.

PMID- 21097376
TI  - Intraoperative brain shift compensation: accounting for dural septa.
AB  - Biomechanical models that describe soft tissue deformation provide a relatively
      inexpensive way to correct registration errors in image-guided neurosurgical
      systems caused by nonrigid brain shift. Quantifying the factors that cause this
      deformation to sufficient precision is a challenging task. To circumvent this
      difficulty, atlas-based methods have been developed recently that allow for
      uncertainty, yet still capture the first-order effects associated with
      deformation. The inverse solution is driven by sparse intraoperative surface
      measurements, which could bias the reconstruction and affect the subsurface
      accuracy of the model prediction. Studies using intraoperative MR have shown that
      the deformation in the midline, tentorium, and contralateral hemisphere is
      relatively small. The dural septa act as rigid membranes supporting the brain
      parenchyma and compartmentalizing the brain. Accounting for these structures in
      models may be an important key to improving subsurface shift accuracy. A novel
      method to segment the tentorium cerebelli will be described, along with the
      procedure for modeling the dural septa. Results in seven clinical cases show a
      qualitative improvement in subsurface shift accuracy making the predicted
      deformation more congruous with previous observations in the literature. The
      results also suggest a considerably more important role for hyperosmotic drug
      modeling for the intraoperative shift correction environment.

PMID- 21097378
TI  - Graph run-length matrices for histopathological image segmentation.
AB  - The histopathological examination of tissue specimens is essential for cancer
      diagnosis and grading. However, this examination is subject to a considerable
      amount of observer variability as it mainly relies on visual interpretation of
      pathologists. To alleviate this problem, it is very important to develop
      computational quantitative tools, for which image segmentation constitutes the
      core step. In this paper, we introduce an effective and robust algorithm for the
      segmentation of histopathological tissue images. This algorithm incorporates the
      background knowledge of the tissue organization into segmentation. For this
      purpose, it quantifies spatial relations of cytological tissue components by
      constructing a graph and uses this graph to define new texture features for image
      segmentation. This new texture definition makes use of the idea of gray-level run
      length matrices. However, it considers the runs of cytological components on a
      graph to form a matrix, instead of considering the runs of pixel intensities.
      Working with colon tissue images, our experiments demonstrate that the texture
      features extracted from "graph run-length matrices" lead to high segmentation
      accuracies, also providing a reasonable number of segmented regions. Compared
      with four other segmentation algorithms, the results show that the proposed
      algorithm is more effective in histopathological image segmentation.

PMID- 21097379
TI  - Multichannel image registration by feature-based information fusion.
AB  - This paper proposes a novel nonrigid inter-subject multichannel image
      registration method which combines information from different modalities/channels
      to produce a unified joint registration. Multichannel images are created using co
      registered multimodality images of the same subject to utilize information across
      modalities comprehensively. Contrary to the existing methods which combine the
      information at the image/intensity level, the proposed method uses feature-level
      information fusion method to spatio-adaptively combine the complementary
      information from different modalities that characterize different tissue types,
      through Gabor wavelets transformation and Independent Component Analysis (ICA),
      to produce a robust inter-subject registration. Experiments on both simulated and
      real multichannel images illustrate the applicability and robustness of the
      proposed registration method that combines information across modalities. This
      inter-subject registration is expected to pave the way for subsequent unified
      population-based multichannel studies.

PMID- 21097380
TI  - Dynamic channel assignment for large-scale cellular networks using noisy chaotic
      neural network.
AB  - This paper presents a novel dynamic channel assignment (DCA) technique for large
      scale cellular networks (LCNs) using noisy chaotic neural network. In this
      technique, an LCN is first decomposed into many subnets, which are designated as
      decomposed cellular subnets (DCSs). The DCA process is independently performed in
      every subnet to alleviate the signaling overheads and to apportion the DCA
      computational load among the subnets. Then a novel energy function is formulated
      to avoid causing mutual interference among neighboring subnets based on the real
      time interference channel table. In each subnet, the proposed energy function
      also satisfies three interference constraints among cells and the number of
      required channels of each cell, and simultaneously minimizes the total number of
      assigned channels to improve spectrum utilization. A typical 441-cell LCN with 70
      available channels, which can be decomposed into nine 49-cell DCSs, is examined
      to demonstrate the validity of the proposed technique by blocking probability,
      including uniform and hot spot traffic patterns.

PMID- 21097381
TI  - Optimized discriminative kernel for SVM scoring and its application to speaker
      verification.
AB  - The decision-making process of many binary classification systems is based on the
      likelihood ratio (LR) scores of test patterns. This paper shows that LR scores
      can be expressed in terms of the similarity between the supervectors (SVs) formed
      by stacking the mean vectors of Gaussian mixture models corresponding to the test
      patterns, the target model, and the background model. By interpreting the support
      vector machine (SVM) kernels as a specific similarity (or discriminant) function
      between SVs, this paper shows that LR scoring is a special case of SVM scoring
      and that most sequence kernels can be obtained by assuming a specific form for
      the similarity function of SVs. This paper further shows that this assumption can
      be relaxed to derive a new general kernel. The kernel function is general in that
      it is a linear combination of any kernels belonging to the reproducing kernel
      Hilbert space. The combination weights are obtained by optimizing the ability of
      a discriminant function to separate the positive and negative classes using
      either regression analysis or SVM training. The idea was applied to both high-and
      low-level speaker verification. In both cases, results show that the proposed
      kernels achieve better performance than several state-of-the-art sequence
      kernels. Further performance enhancement was also observed when the high-level
      scores were combined with acoustic scores.

PMID- 21097382
TI  - Automatically detecting pain in video through facial action units.
AB  - In a clinical setting, pain is reported either through patient self-report or via
      an observer. Such measures are problematic as they are: 1) subjective, and 2)
      give no specific timing information. Coding pain as a series of facial action
      units (AUs) can avoid these issues as it can be used to gain an objective measure
      of pain on a frame-by-frame basis. Using video data from patients with shoulder
      injuries, in this paper, we describe an active appearance model (AAM)-based
      system that can automatically detect the frames in video in which a patient is in
      pain. This pain data set highlights the many challenges associated with
      spontaneous emotion detection, particularly that of expression and head movement
      due to the patient's reaction to pain. In this paper, we show that the AAM can
      deal with these movements and can achieve significant improvements in both the AU
      and pain detection performance compared to the current-state-of-the-art
      approaches which utilize similarity-normalized appearance features only.

PMID- 21097383
TI  - Diagnosis of cardiovascular abnormalities from compressed ECG: a data mining
      based approach.
AB  - Usage of compressed ECG for fast and efficient telecardiology application is
      crucial, as ECG signals are enormously large in size. However, conventional ECG
      diagnosis algorithms require the compressed ECG packets to be decompressed before
      diagnosis can be performed. This added step of decompression before performing
      diagnosis for every ECG packet introduces unnecessary delay, which is undesirable
      for cardiovascular diseased (CVD) patients. In this paper, we are demonstrating
      an innovative technique that performs real-time classification of CVD. With the
      help of this real-time classification of CVD, the emergency personnel or the
      hospital can automatically be notified via SMS/MMS/e-mail when a life-threatening
      cardiac abnormality of the CVD affected patient is detected. Our proposed system
      initially uses data mining techniques, such as attribute selection (i.e., selects
      only a few features from the compressed ECG) and expectation maximization (EM)
      based clustering. These data mining techniques running on a hospital server
      generate a set of constraints for representing each of the abnormalities. Then,
      the patient's mobile phone receives these set of constraints and employs a rule
      based system that can identify each of abnormal beats in real time. Our
      experimentation results on 50 MIT-BIH ECG entries reveal that the proposed
      approach can successfully detect cardiac abnormalities (e.g., ventricular
      flutter/fibrillation, premature ventricular contraction, atrial fibrillation,
      etc.) with 97% accuracy on average. This innovative data mining technique on
      compressed ECG packets enables faster identification of cardiac abnormality
      directly from the compressed ECG, helping to build an efficient telecardiology
      diagnosis system.

PMID- 21097385
TI  - A distribution-based multiple imputation method for handling bivariate pesticide
      data with values below the limit of detection.
AB  - BACKGROUND: Environmental and biomedical researchers frequently encounter
      laboratory data constrained by a lower limit of detection (LOD). Commonly used
      methods to address these left-censored data, such as simple substitution of a
      constant for all values < LOD, may bias parameter estimation. In contrast,
      multiple imputation (MI) methods yield valid and robust parameter estimates and
      explicit imputed values for variables that can be analyzed as outcomes or
      predictors. OBJECTIVE: In this article we expand distribution-based MI methods
      for left-censored data to a bivariate setting, specifically, a longitudinal study
      with biological measures at two points in time. METHODS: We have presented the
      likelihood function for a bivariate normal distribution taking into account
      values < LOD as well as missing data assumed missing at random, and we use the
      estimated distributional parameters to impute values < LOD and to generate
      multiple plausible data sets for analysis by standard statistical methods. We
      conducted a simulation study to evaluate the sampling properties of the
      estimators, and we illustrate a practical application using data from the
      Community Participatory Approach to Measuring Farmworker Pesticide Exposure
      (PACE3) study to estimate associations between urinary acephate (APE)
      concentrations (indicating pesticide exposure) at two points in time and self
      reported symptoms. RESULTS: Simulation study results demonstrated that imputed
      and observed values together were consistent with the assumed and estimated
      underlying distribution. Our analysis of PACE3 data using MI to impute APE values
      < LOD showed that urinary APE concentration was significantly associated with
      potential pesticide poisoning symptoms. Results based on simple substitution
      methods were substantially different from those based on the MI method.
      CONCLUSIONS: The distribution-based MI method is a valid and feasible approach to
      analyze bivariate data with values < LOD, especially when explicit values for the
      nondetections are needed. We recommend the use of this approach in environmental
      and biomedical research.

PMID- 21097386
TI  - Role of the oral Beta-lactams in the treatment of exacerbations of chronic
      bronchitis: critical analysis and therapeutics recommendations.

PMID- 21097384
TI  - Global influenza seasonality: reconciling patterns across temperate and tropical
      regions.
AB  - BACKGROUND: Despite the significant disease burden of the influenza virus in
      humans, our understanding of the basis for its pronounced seasonality remains
      incomplete. Past observations that influenza epidemics occur in the winter across
      temperate climates, combined with insufficient knowledge about the epidemiology
      of influenza in the tropics, led to the perception that cool and dry conditions
      were a necessary, and possibly sufficient, driver of influenza epidemics. Recent
      reports of substantial levels of influenza virus activity and well-defined
      seasonality in tropical regions, where warm and humid conditions often persist
      year-round, have rendered previous hypotheses insufficient for explaining global
      patterns of influenza. OBJECTIVE: In this review, we examined the scientific
      evidence for the seasonal mechanisms that potentially explain the complex
      seasonal patterns of influenza disease activity observed globally. METHODS: In
      this review we assessed the strength of a range of hypotheses that attempt to
      explain observations of influenza seasonality across different latitudes and how
      they relate to each other. We reviewed studies describing population-scale
      observations, mathematical models, and ecological, laboratory, and clinical
      experiments pertaining to influenza seasonality. The literature review includes
      studies that directly mention the topic of influenza seasonality, as well as
      other topics we believed to be relevant. We also developed an analytical
      framework that highlights the complex interactions among environmental stimuli,
      mediating mechanisms, and the seasonal timing of influenza epidemics and identify
      critical areas for further research. CONCLUSIONS: The central questions in
      influenza seasonality remain unresolved. Future research is particularly needed
      in tropical localities, where our understanding of seasonality remains poor, and
      will require a combination of experimental and observational studies. Further
      understanding of the environmental factors that drive influenza circulation also
      may be useful to predict how dynamics will be affected at regional levels by
      global climate change.

PMID- 21097387
TI  - Description of the disease and diagnostic and epidemiologic aspects.

PMID- 21097388
TI  - Etiology issues and problems of antibiotic resistance.

PMID- 21097389
TI  - Pharmacological and pharmaeconomic considerations.

PMID- 21097390
TI  - Conclusions. Role of the oral Beta-lactams in the treatment of exacerbations of
      chronic bronchitis: critical analysis and therapeutics recommendations.

PMID- 21097391
TI  - Convulsions associated with gastroenteritis in the spectrum of benign focal
      epilepsies in infancy: 30 cases including four cases with ictal EEG recording.
AB  - Benign convulsions associated with gastroenteritis are now recognized as a
      clinical entity, characterized by an acute cluster of afebrile seizures during an
      episode of mild diarrhoea with excellent prognosis. We observed 30 children who
      each experienced at least two seizures associated with mild gastroenteritis. The
      inclusion criteria were: afebrile seizures during gastroenteritis, dehydration at
      <= 5%, normal neurological findings, normal psychomotor development and no
      underlying pathology according to laboratory and neuroimaging studies. Mean age
      was 21 months (range: 6-38). Familial history for epilepsy was positive in 3/30
      (10%) and for febrile convulsions in 11/30 (36.6%). Seizure onset was mainly on
      the third day of gastroenteritis. Seizures were described as generalised by
      parents in 16/30 patients (53.3%). We directly observed seizures in 14/30
      patients (47.7%), and the semiology was partial with secondary generalisation.
      Focal onset was confirmed in two patients by EEG and in two patients by video-EEG
      recording. Twenty of 30 patients (66.6%) received antiepileptic drugs during the
      acute phase. Ten patients (33.3%) received no treatment. During follow-up (mean
      duration: 53 months), one patient had an isolated afebrile seizure and two others
      a febrile seizure. At the end of follow-up, antiepileptic treatment was withdrawn
      for all but two patients. None developed epilepsy. Although the pathogenesis of
      this clinical entity is unknown, we hypothesize that mild gastroenteritis may
      provoke a transient brain dysfunction which in turn provokes seizures in children
      with genetically determined susceptibility.

PMID- 21097392
TI  - Identification of specific tumor necrosis factor-alpha-susceptible and 
      protective haplotypes associated with the risk of type 1 diabetes.
AB  - AIM: We investigated the association of tumor necrosis factor (TNF)alpha gene
      polymorphism with type 1 diabetes (T1D). METHODS: TNF-alpha -1031T/C, -863C/A, 
      857C/T, -376G/A, -308G/A, -238G/A, and +488G/A single nucleotide polymorphisms
      (SNPs) were assessed in 198 T1DM patients and 180 age-and gender-matched,
      normoglycemic control subjects using PCR-restriction fragment length polymorphism
      (RFLP). RESULTS: Higher frequencies of -863A (p = 8.0 * 10-6), -857T (p = 1.4 *
      10-4), and -238A (p = 0.002) alleles were seen in T1D patients than in the
      control group. Significant differences were noted in the distribution of -863T/C,
      -857C/T, -376G/A, -308G/A, and -238G/A genotypes between patients and controls.
      Haploview analysis revealed high linkage disequilibrium (LD) between the -376G/A
      and -308G/A SNPs, but this was lower between the other polymorphisms. Five-locus
      TNFalpha haplotypes were constructed based on the prevalence of individual SNPs
      and the LD between them. An increased frequency of CTGGG, CCGAG, and ACGGG
      haplotypes, and a reduced frequency of the CCGGG haplotype was seen in patients.
      When the Bonferroni correction was applied, differences were significant for the
      CTGGG (Pc = 1.4 * 10-3), CCGAG (Pc = 0.023), and ACGGG (Pc = 1.2 * 10-3)
      haplotypes which were greater, and the CCGGG haplotype (Pc = 3.8 * 10-5) which
      was smaller, among T1D patients, thereby conferring susceptibility to and
      protection from T1D, respectively. CONCLUSION: These results demonstrate that TNF
      alpha polymorphisms, in particular -863C/A, -857C/T, and -238G/A, are
      significantly associated with T1D. Additional studies, on other racial groups,
      are needed to confirm our findings.

PMID- 21097393
TI  - Tissue-specific expression of IL-15RA alternative splicing transcripts and its
      regulation by DNA methylation.
AB  - The human IL-15RA gene encoding the alpha chain of the IL-15 receptor is
      expressed in a variety of immune and non-immune cell types from different
      tissues, and generates multiple splicing events of functional importance. We
      aimed to evaluate expression of IL-15RA transcripts generated by alternative
      usage of transcription start site (Var1 and Var2) and by deletion of exon 3
      (Del3), exon 2 (Del2), or both (Del2,3) in different human tissues. Since a CpG
      island was found near to the IL-15RA gene transcription start site, we also
      investigated the role of DNA methylation on the expression of IL-15RA full-length
      and alternative transcripts fragments in peripheral blood mononuclear cells
      (PBMC). IL-15RA transcription of functional (full-length and del 3) and non
      functional (del 2 and del 2,3) variants was detected in many tissues, however,
      the number of different IL-15RA transcripts variants detected in each tissue did
      not correlate with the level of gene expression. IL-15RA transcript variants Var1
      and Var2 presented similar expression levels in different human tissues. However,
      we found a distinct expression profile of functional and non-functional IL-15RA
      transcripts fragments. A preferential expression of transcripts that bind IL-15
      compared to IL-15 non-binding transcripts was seen in the tissues investigated.
      When PBMC cultures were treated with 5-azacitidine (AZA), a DNA methyltransferase
      inhibitor, we detected a significant increase in IL-15RA copy number. Only
      alternative exon skipping events of Var1 (Del 2, Del 3 and Del 2, 3) were altered
      by AZA treatment, which is consistent with the CpG island localization in the
      regulatory region 5' upstream of the transcription start site of Var1 and not of
      Var2. Therefore, this work shows a broad expression pattern of functional IL-15RA
      splicing forms and suggests a regulatory role of DNA methylation in IL-15RA
      transcript Var1 expression in mononuclear cells.

PMID- 21097394
TI  - [Effects of AMPK on the transcriptional activity of FOXO1 and ubiquitin ligase
      MuRF1 expression in rat cardiomyocytes].
AB  - OBJECTIVE: To investigate the effects of AICAR on the activity of transcription
      factor FOXO1 and expression of ubiquitin ligase MuRF1 in rat cardiomyocytes, and
      explore the possible role of AMP-activated protein kinase (AMPK) in proteolysis
      pathways. METHODS: In vitro cultured neonatal rat cardiac myocytes were treated
      with AICAR, and Western blotting was used to detect the phosphorylation of FOXO1
      and expression of MuRF1 in the cells. RESULTS: AICAR activated AMPK in rat
      cardiac myocytes. Activated AMPK significantly inhibited the phosphorylation of
      FOXO1 and increased MuRF1 protein expression. CONCLUSION: AMPK may regulate
      proteolysis by activating FOXO1 transcription factor and up-regulating MuRF1
      expression.

PMID- 21097395
TI  - [Short-term outcomes of 16 patients with non-small cell lung cancer receiving
      cetuximab combined with standard chemotherapy in the first and non-first line
      settings].
AB  - OBJECTIVE: To summarize our experiences with the treatment of non-small cell lung
      cancer (NSCLC) with cetuximab and compare the therapeutic effects of cetuximab
      applied in the first line and non-first line settings. METHODS: From October 1,
      2006 to December 31, 2009, 16 NSCLC patients were treated with cetuximab combined
      with standard chemotherapy in Sun Yat-sen University Cancer Center. The short
      term efficacy of the therapeutic protocols were analyzed. RESULTS: A total of 115
      cycles of cetuximab treatment were administered in these patients with a median
      of 6 cycles (7.5 in the first line setting and 2 in non-first line setting). In
      the 10 patients with cetuximab treatment in the first line setting, the ORR was
      40.0% (4/10), DCR was 80.0% (8/10), median TTP was 6.5 months (2-19), and median
      OS was 8.5 months (2-48); in the non-first line setting, these indices were 33.3%
      (2/6), 33.3% (2/6), 3.5 months (3-4) and 18 months (4-28), respectively. Both ORR
      and DCR were similar between the first and non-first line settings (P=0.790,
      P=0.062). Ten of the patients (62.5%) developed acne-like rash within 3 weeks,
      who had an ORR of 60% (6/10) and DCR of 90% (9/10); the ORR and DCR in patients
      without acne-like rash were both 10.4% (1/6), showing no significant difference
      in ORR (P=0.080) but a significant difference in DCR between the two groups
      (P=0.003). No treatment-associated death or cetuximab-associated discontinuation
      occurred. Altogether 11 patients (68.8%) developed acne-like rash, which occurred
      within 3 weeks in 10 cases. Seven patients showed side effects associated with
      the chemotherapy. CONCLUSION: Cetuximab combined with standard chemotherapy is a
      good option for Chinese patients with NSCLC and the current data support the
      application of cetuximab in the first line setting.

PMID- 21097396
TI  - [Construction of let-7a expression plasmid and its inhibitory effect on k-Ras
      protein in A549 lung cancer cells].
AB  - OBJECTIVE: To elucidate the role of let-7a-mediated gene regulation in the
      pathogenesis of lung cancer. METHODS: Two template DNA sequences were designed
      based on hsa-let-7a sequence in miRBase database. The let-7a expression construct
      and a control plasmid, namely pGenesil-let-7a and pGenesil-control, respectively,
      were generated by cloning the annealed oligonucleotides into pGenesil-1 and then
      transfected into A549 cells, which were selected by G418 to establish the lung
      cancer cell lines stably expressing let-7a-GFP and control-GFP. The living cells
      were counted by MTT assay and cell growth curves were drawn to analyze the cell
      proliferation. The k-Ras mRNA level was assessed by semi-quantitative RT-PCR, and
      the expression of k-Ras protein was determined by Western blotting and
      immunocytochemistry. RESULTS: The recombinant vectors were verified by
      sequencing. The cell growth curves indicated that the proliferation of the cells
      transfected with pGenesil- let-7a were inhibited significantly compared with that
      of cells transfected with pGenesil-control and A549 cells. Semi- quantitative RT
      PCR analysis showed that the levels of k-Ras mRNA almost remained unchanged in
      cells with or without the treatments. Western blotting and immunocytochemistry
      demonstrated a significant decrease of k-Ras protein levels in cells transfected
      with pGenesil-let-7a, but not in cells transfected with pGenesil-control, when
      compared to A549 cells. CONCLUSION: let-7a over-expression represses the
      expression of k-Ras protein and significantly inhibits the growth of lung cancer
      cells.

PMID- 21097397
TI  - [Construction and identification of a RNA interference plasmid for rat BNIP3
      gene].
AB  - OBJECTIVE: To construct a RNA interfering plasmid targeting rat Bcl-2/E1B-19K
      interacting protein 3 (BNIP3) and assess its effect on exogenous BNIP3 expression
      in HEK293 cells. METHODS: The miRNA sequences were designed using Invitrogen
      BLOCK-iT RNAi Designer and synthesized into double-strand oligonucleotides, which
      were cloned into the pcDNATM6.2-GW/EmGFP-miR vector, followed by transformation
      of the product into competent Top10 E. coli cells. After expansion of the
      transformed bacteria, the plasmid was extracted and sequenced before its co
      transfection with pEGFP-C3- rBNIP3 plasmid into HEK293 cells. The interference
      effect of the constructed plasmid on BNIP3 mRNA and protein expression were
      detected by real-time PCR and Western blotting. RESULTS: The sequencing result
      indicated that the interfering plasmid targeting rat BNIP3 was constructed
      correctly. After transfection into HEK293 cells, the interfering plasmid
      significantly inhibited exogenous BNIP3 mRNA and protein expressions. CONCLUSION:
      The RNA interfering plasmid targeting rat BNIP3 has been constructed
      successfully, which provides a useful tool for studying the function of BNIP3.

PMID- 21097398
TI  - [Lithium chloride combined with human umbilical cord blood mesenchymal stem cell
      transplantation for treatment of spinal cord injury in rats].
AB  - OBJECTIVE: To observe the effects of lithium chloride combined with human
      umbilical cord blood mesenchymal stem cell (hUCB-SCs) transplantation in the
      treatment of spinal cord injury in rats. METHODS: Eighty female SD rats with
      complete T9 spinal cord transaction were randomized into 4 groups (n=20), namely
      the control group (group A), lithium chloride group (group B), hUCB-SCs group
      (group C) and hUCB-SCs(+) lithium chloride group (group D). On days 1 and 3 and
      the last days of the following weeks postoperatively, the motor function of the
      hindlimb of the rats were evaluated according to the BBB scores. At 8 weeks, all
      the rats were sacrificed and the spinal cords were taken for morphological
      observation. The spinal cord tissues at the injury site were observed with Brdu
      nuclear labeling to identify the survival and migration of the transplanted SCs.
      The regeneration and distribution of the spinal nerve fibers were observed with
      fluorescent-gold (FG) spinal cord retrograde tracing. RESULTS: Brdu labeling
      showed that the transplanted hUCB-SCs survived and migrated in the spinal cord 8
      weeks postoperatively in groups C and D. FG retrograde tracing identified a small
      amount of pyramidal cells that migrated across the injury site in groups C and D.
      The BBB scores of the hindlimb motor function 8 weeks postoperatively were
      4.11?0.14, 4.50?0.15, 8.31?0.11 and 11.15?0.18 in groups A, B, C and D,
      respectively. CONCLUSION: Lithium chloride can promote the survival and
      differentiation of hUCB-SCs into neural cells at the injury site. Lithium
      chloride combined with hUCB-SCs transplantation may accelerate functional
      recovery of the hindlimbs in rats with complete transection of the spinal cord.

PMID- 21097399
TI  - [Mechanisms of resveratrol bovine serum albumin nanoparticle-induced cell death
      in human ovarian cancer SKOV3 cells].
AB  - OBJECTIVE: To study the effect of resveratrol bovine serum albumin nanoparticles
      on SKOV3 cell line and its mechanisms. METHODS: The morphological changes of the
      cells exposed to the nanoparticles were observed by apoptotic body/cell nucleus
      DNA staining under inverted microscope and fluorescence microscope, and the
      pathway of cell death was determined by phosphatidylserine translocation. Western
      blotting was performed to detect the activation of cyto.c, caspase-3 and caspase
      9. RESULTS: DNA ladder was detected with gel electrophoresis and the cell death
      was partially inhibited by the pan-caspase inhibitor Z-VAD-FMK. Gel
      electrophoresis displayed both DNA ladder and smear in RES-BSANP exposed groups,
      while DNA ladder disappeared in Z-VAD-FMK group and only the smear was left.
      Cyto.c in the cytoplasm was released at 2 h, while the expression of caspase-9
      protein reached the peak level at 4 h and caspase-3 expression was obvious
      enhanced at 8 h. At 4 h, caspase-9 expression in the cells exposed to 100 umol/L
      RES-BSANP was decreased significantly as compared to the cells treated with 50
      umol/L RES-BSANP (P>0.05). CONCLUSION: RES-BSANP can induce the necrosis and
      apoptosis of SKOV3 cells via either caspase-dependent or caspase-independent
      pathways.

PMID- 21097400
TI  - [Effect of Sanhuangyinchi decoction on liver damage and caspase-3 in rats with
      acute hepatic failure].
AB  - OBJECTIVE: To investigate effect of Sanhuangyinchi decoction (SHYCD) on liver
      damage and the pro-apoptotic factor caspase-3 in rats with acute hepatic failure.
      METHODS: SD rats were randomly divided into blank control group, model group,
      Angongniuhuang group (AGNH) and SHYCD group. Acute hepatic failure was induced in
      the rats by intraperitoneal injections of D-GaLN and LPS, and the death rate,
      ALT, TBIL, PT and caspase-3 activity was observed or tested. RESULTS: At 36 h
      after the injections, the death rate of the rats was 74.29% (26/35) in the model
      group, 31.43% (11/35) in AGNH group and 28.57%(10/35) in SHYCD group. The death
      rate, ALT, TBIL, PT and caspase-3 activity in AGNH and SHYCD groups were
      significantly lower than those in the model group (P<0.01). SHYCD showed stronger
      effect than AGNH in depressing TBIL and the activity of caspase-3 (P<0.05).
      CONCLUSION: SHYCD can improve the liver function and inhibit the activity of
      caspase-3 in rats, which can be the possible mechanism for its therapeutic effect
      against acute hepatic failure.

PMID- 21097401
TI  - [Clinical implications of HLA-G protein expression in acute leukemia].
AB  - OBJECTIVE: To detect the expression of membrane-bound HLA-G (mHLA-G) and serum
      HLA-G (sHLA-G) in acute leukemia patients and investigate the correlation between
      HLA-G expression and the occurrence and development of acute leukemia. METHODS:
      Enzyme-linked immunosorbent assay and flow cytometry were used to detect the
      expression levels of sHLA-G and mHLA-G in 40 newly diagnosed leukemia cases, 10
      refractory and relapsed leukemia cases, and 30 leukemia cases receiving
      chemotherapy. Ten normal individuals served as the normal control group. RESULTS:
      The mean serum level of sHLA-G in normal individuals was 5.87+/-2.07 ng/ml, as
      compared to 10.05+/-6.58 ng/ml in newly diagnosed leukemia patients and 12.32+/
      5.85 ng/ml in refractory and relapsed cases. The mean level of mHLA-G in normal
      individuals, newly diagnosed cases, and refractory and relapsed cases were
      (0.29+/-0.20)%, (0.60+/-0.44)%, and (0.77+/-0.41)%, respectively. The mean levels
      of sHLA-G and mHLA-G were significantly higher in the newly diagnosed cases than
      that in the normal controls (P<0.05), and significantly higher in patients before
      chemotherapy than in those with complete remission after chemotherapy (P<0.05).
      CONCLUSION: HLA-G expression levels might influence the treatment outcomes and
      can serve as a prognostic factor for acute leukemia.

PMID- 21097402
TI  - [Effect of Shuganlipi decoction on Th1/Th2 cytokines in patients with chronic
      hepatitis B].
AB  - OBJECTIVE: To investigate the effect of Shuganlipi decoction on Th1/Th2
      cytokines, liver function and HBV replication in patients with chronic hepatitis
      B (CHB). METHODS: Eighty-six confirmed CHB cases were randomly divided into
      control group (n=42) and experimental group (n=44) for treatment with routine
      western medication and additional treatment with Shuganlipi decoction,
      respectively. The production of IFN-gamma, IL-2, IL-6, IL-10 and liver function,
      HBV DNA, and HBeAg were detected in all the patients. RESULTS: The total response
      rate to the treatment was significantly higher in the experimental group than in
      the control group (78.13% vs 57.14%, P<0.01). ALT, AST, TBIL and ALB were all
      improved obviously in the two groups after the treatments (P<0.01). In terms of
      ALT and ALB, the experimental group showed more obvious improvement than the
      control group(P<0.05). The treatments also resulted in significant increases of
      IFN-gamma and IL-2 levels and reductions of IL-6 and IL-10 levels in the two
      groups (P<0.01). CONCLUSION: Shuganlipi decoction can improve the liver function
      and activity of Th1/Th2 cytokines to promote the clearance of liver cell HBV
      infection.

PMID- 21097403
TI  - [Construction of MHV-A59 damp-heat mouse model and analysis of the relevant
      indices].
AB  - OBJECTIVE: To explore the impact of inflammation, water metabolism and immune
      function on the establishment of a mouse model of damp-heat syndrome with MHV-A59
      infection. METHODS: Twenty-four mice were randomly divided into control group,
      virus group, damp-heat group and model group. The peripheral blood CD4(+) and
      CD8(+) lymphocytes were detected by flow cytometry, and the serum levels of IFN
      gamma and IL-4 were assayed by ELISA. The expressions of NF-kappaB and AQP4 in
      the liver and stomach were determined using immunohistochemistry. RESULTS: The
      expression of NF-kappaB and CD4(+)/CD8(+) ratio in the virus and model groups
      were significantly higher than those in the damp-heat and control groups, while
      the expression of AQP4 was significantly higher in the model and damp-heat groups
      than in the other groups. Compared with the control group, the model group showed
      a significantly higher ratio of IFN-gamma/IL-4. CONCLUSIONS: MHV-A59 virus is the
      main cause of elevated NF-kappaB expression and CD4(+)/CD8(+)/ ratio, while damp
      heat syndrome is responsible for increased AQP4 expression, and their synergistic
      effect results in increased IFN-gamma/IL-4 ratio. The mouse model established
      using MHV-A59 virus and the damp-heat factors can mimic damp-heat syndrome
      described in traditional Chinese medicine theory.

PMID- 21097404
TI  - [Lumbar interspinous non-fusion techniques: comparison between CoflexTM and
      Wallis].
AB  - OBJECTIVE: To compare the short-term clinical outcome of non-fusion techniques
      using interspinous implantation Coflex(TM) and Wallis treatment in patients with
      lumbar spine degenerative diseases. METHODS: Forty-one cases of lumbar stenosis,
      18 of lumbar disc herniation, and 34 of lumbar stenosis with lumbar disc
      herniation were evaluated. Among the 43 cases receiving Coflex(TM) implantation,
      41 had operations in one segment and 2 in 2 segments. In the other 50 cases with
      Wallis implantation, 47 had fixation of 1 segment and 3 had 2 segments fixed. JOA
      Score, Oswestry Disable Index (ODI) and VAS were used to evaluate the short-term
      clinical results. RESULTS: The average operating time was 64.55 min in Coflex(TM)
      implantation with an average blood loss of 81.82 ml. The average operating time
      was 82.71 min in Wallis implantation, which caused an average blood loss of 89.66
      ml. Significant improvements in the JOA Score, ODI and VAS were noted after the
      operations. CONCLUSION: The two interspinous non-fusion techniques, Coflex and
      Wallis, produce good short-term clinical outcome in the treatment of lumbar spine
      degenerative diseases.

PMID- 21097405
TI  - [Correlation of microalbuminuria and fibrinogen to the severity of coronary
      artery lesions in patients with metabolic syndrome].
AB  - OBJECTIVE: To investigate the correlation of microalbuminuria (MA) and fibrinogen
      (Fib) to the severity of coronary artery lesions in patients with metabolic
      syndrome (MS). METHODS: Eighty-five patients with MS undergoing coronary artery
      angiography were divided, according to the number of vessels involved, into
      multivessel disease group and non-multivessel disease group, and also according
      to the modified Gensini score, into severe lesion (Gensini score>20) and non
      severe lesion group. The correlations of MA and Fib to the number of involved
      vessels and the severity of the lesions were analyzed. RESULTS: The urinary
      albumin to creatinine ratio (ACR) and Fib were significantly different between
      the multivessel and non-multivessel disease groups (P<0.05), and were found to be
      positively correlated to the number of coronary artery lesion (r=0.378, P=0.000;
      r=0.327, P=0.002). ACR, Fib, sex, smoking history and HDL-C differed
      significantly between severe lesion and non-severe lesion groups (P<0.05), and
      ACR and Fib showed positive correlations to the Gensini score (r=0.337, P=0.002;
      r=0.286, P=0.008). Logistic regression analysis identified ACR as an independent
      predictor of multivessel disease (B=2.655, P=0.000) and Gensini score (B=1.803,
      P=0.009), independent of sex, age, body mass index, smoking history, diabetes
      mellitus, LDL-C and HDL-C. CONCLUSION: MA and Fib are positively correlated to
      the severity of coronary artery lesion, and MA is an independent predictor of
      multivessel disease and Gensini score in patients with MS.

PMID- 21097407
TI  - [Three-dimensional finite element analysis of biomechanical characteristics of
      cancellous screw in different bone densities].
AB  - OBJECTIVE: To predict the cancellous screw stress distributions and pull-out
      strength in cancellous bone with different densities using 3-D finite element
      analysis and provide biomechanical evidence for screw implant in clinical
      practices. METHODS: Three-dimensional models of bones with low, medium and high
      bone density and a fixation screw were generated in Solidworks. Finite element
      analysis was performed after importing these models to Abaqus to simulate the
      pull- out process. RESULTS: Stress concentrated both at the surfaces where major
      diameter of the screw connected the bone and at the proximal half angle of the 3
      proximal screw threads. Maximum Von Mises stress of the threads decreased along
      the long axis of the screw. The pull-out strengths of the cancellous screw were
      208.9 N, 431.45 N, and 648.80 N in low, medium and high bone density,
      respectively. CONCLUSION: During the pull-out process of cancellous screw, stress
      concentrates at the proximal end of the screw and the pull-out strengths are
      proportional to the cancellous bone density.

PMID- 21097406
TI  - [In vivo and in vitro stability of 131I-Herceptin and its form of existence in
      the blood of rabbits].
AB  - OBJECTIVE: To evaluate the in vivo and in vitro stability of (131)I-Herceptin and
      its form of existence in the blood. METHODS: Herceptin was labelled with iodine
      131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius
      for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by
      high performance liquid chromatography (HPLC). Five rabbits received injections
      of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection,
      blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and
      the radio count of the serum and blood cells was calculated. RESULTS: The
      baseline RCP of (131)I-Herceptin was (94.9+/-2.7)%. The RCP was stable after
      placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was
      significantly lowered to (82.6+/-2.8)% after preservation for over 72 h (t=9.971,
      P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I
      Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after
      the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered
      to (75.4+/-3.9)% (t=6.564, P<0.001). CONCLUSION: Storage at 4 degrees celsius for
      no more than 72 h does not obviously affect the activity of (131)I-Herceptin in
      terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the
      serum and its radiochemical purity remains stable within 24 h, after which
      obvious degradation occurs.

PMID- 21097408
TI  - [Value of ultrasono-portography using SonoVue in selective portal vein
      embolization].
AB  - OBJECTIVE: To explore the value of ultrasono-portography using SonoVue in
      selective portal vein embolization (SPVE). METHODS: Twenty-eight patients with
      malignant liver tumors underwent percutaneous ultrasound-guided SPVE. The
      procedure was performed under color Doppler ultrasound guidance in 11 cases
      (conventional group) and under guidance with ultrasono-portography using SonoVue
      in 17 cases (contrast group). Contrast-enhanced CT was performed 2-4 weeks after
      SPVE to evaluate the effect of embolization. RESULTS: The procedure of SPVE was
      aborted in 3 cases in which ultrasono-portography showed contraindications.
      Postoperative contrast-enhanced CT showed ectopic embolization in 2 cases in the
      conventional group, and none of the cases in the contrast group showed ectopic
      embolization. CONCLUSION: Ultrasono-portography using SonoVue can provide
      important assistance for SPVE.

PMID- 21097409
TI  - [Development of a DNA microarray for detecting 8 common species of food-borne
      bacterial pathogens in south China].
AB  - OBJECTIVE: To prepare a DNA Microarray that can detect 8 common species of food
      borne bacterial pathogens in south China. METHODS: All the 70mer oligo probes
      were designed on the characteristic genome loci of the 8 species of food borne
      bacterial pathogens. Eight subarrays corresponding to the 8 food borne bacterial
      pathogens were spotted onto the slide and integrated into a pan-array on the
      chip. A number of identified and known bacterial samples from the storage bank
      were selected for the validation test. RESULTS: Based on the PPR ranking, for LM
      sub-array, the PPR of the 3 Listeria bacteria LM, Lin and Liv was 68.8%, 51.8%
      and 59.6%, respectively, while that of the non-Listeria bacterial samples was all
      below 43%. For VC sub-array, the PPR of VC sample was 54.1% and that of the non
      VC bacterial samples was lower than 17.2%. For VP sub-array, the PPR was 66.7%
      for VP sample and below 24.2% for non-VP bacterial samples. For Sal sub-array,
      the PPR was 55.9% for Sal sample and below 50.5% for non-Sal bacterial samples.
      For Shi sub-array, the PPR of Shi sample and the non-Shi bacterial samples was
      53.8% and below 36.6%, respectively. For SA sub-array, the PPR of SA sample and
      non-SA bacterial samples was 65.2% and below 22.7%, respectively. For CJ sub
      array, the PPR of the 2 Campylobacter bacteria CJ and CC were 88.2% and 58.8%,
      respectively, and that of the non-Campylobacter bacterial samples was lower than
      35.3%. For EC sub-array, the PPR of EC sample was 47.9%, and that of the non-EC
      bacterial samples was lower than 41.6%. Evaluation of the Biosafood-8 chip
      developed in this study by 18 biological samples from different origins
      demonstrated its good specificity and accuracy in the identification of the
      pathogens. CONCLUSION: The chip we developed can clearly differentiate the target
      food borne pathogenic bacteria and non-target bacteria and allows specific and
      accurate identification of the species of the tested bacteria isolates.

PMID- 21097410
TI  - [Preparation and biocompatibility evaluation of osteochondral composite
      scaffold].
AB  - OBJECTIVE: To prepare osteochondral composite scaffold and study its
      biocompatibility in vitro. METHODS: The composite material of nano-HAP/collagen I
      was prepared, and the osteochondral scaffold was manufactured by combining nano
      HAP, collagen I, and PLGA as the bone section and sodium hyaluronate and PLGA as
      the chondral section. The diameter, chemical composition and crystallinity of the
      nano-HAP/collagen I composite particles were assessed with TEM, FTIR and XRD, and
      the biocompatibility and cytotoxicity of the scaffold were evaluated using MTT
      assay by co-culturing bone marrow stem cells and the scaffold. RESULTS AND
      CONCLUSION: The osteochondral composite scaffold has good microstructure without
      obvious cytotoxicity, possesses good biocompatibility with bone marrow stem cells
      and is suitable as an osteochondral scaffold material.

PMID- 21097411
TI  - [Transforming of the drug resistance plasmid from Staphylococcus aureus into
      Escherichia coli].
AB  - OBJECTIVE: To discuss the possible mechanism of drug resistance transmission
      between Staphylococcus and Escherichia coli. METHODS: The chloramphenicol
      resistance plasmid of Staphylococcus aureus was extracted to transform the
      sensitive Escherichia coli, and the drug-resistant Escherichia coli were screened
      by drug sensitivity test. RESULTS: The drug-resistant Escherichia coli were
      successfully obtained. CONCLUSION: Staphylococcus may have a natural shuttle
      plasmid of drug resistance, which can transform Escherichia coli under specific
      conditions.

PMID- 21097412
TI  - [Video-assisted thoracoscopic radical resection of early-stage non-small cell
      lung cancer].
AB  - OBJECTIVE: To study the reliability and feasibility of video-assisted
      thoracoscopic surgery (VATS) for radical resection of early-stage non-small cell
      lung cancer (NSCLC). METHODS: Fifty-four patients with NSCLC treated between Jan.
      2007 and Jun. 2010 at our institution were divided into VATS group (n=23) and
      video-assisted mini thoracotomy (VAMT) group (n=31). The operative time,
      intraoperative blood loss, number of dissected nodes, pleural effusion drainage,
      postoperative hospital stay, and visual analogue scales (VAS) were compared
      between the two groups. RESULTS: No deaths or serious complications occurred
      perioperatively in the two groups. The operative time, intraoperative blood loss,
      number of dissected lymph nodes or pleural effusion drainage were all comparable
      between the two groups, but compared with VAMT, VATS was associated with
      significantly shortened postoperative hospital stay (10.54+/-1.21 days vs 7.92+/
      0.86 days, P<0.05) and lowered VAS scores (4.26+/-1.28 vs 2.37+/-0.25, P<0.05).
      CONCLUSION: VATS for pulmonary lobe resection with systematic node dissection is
      a feasible approach to the management of early-stage NSCLC.

PMID- 21097413
TI  - [Case-control study of the risk factors of lumbar intervertebral disc herniation
      in 5 northern provinces of China].
AB  - OBJECTIVE: To explore the risk factors of lumbar intervertebral disc herniation
      in the 5 northern provinces of China. METHODS: A total of 2010 patients with
      established diagnosis of lumbar disc herniation by CT and/or MRI and 2170 control
      subjects without a history of low back pain or sciatica were randomly selected
      from the community population and hospitalized patients. The family history of
      lumbar disc herniation, occupations, smoking status, and occupational
      psychosocial factors were investigated. RESULTS: The positivity of family history
      of lumbar disc herniation was the highest risk factor (OR=3.551) followed by
      lumbar load (OR=2.132) and hard work (OR=1.763). Physical exercises (OR=0.435)
      were significantly related with the disease, and the OR of the type of bed was
      0.364. CONCLUSION: A family history of lumbar disc herniation, lumbar load and
      hard work are the major risk factors for lumbar disc herniation, and physical
      exercises and sleeping not in soft bed might be a protective factor against the
      disease.

PMID- 21097414
TI  - [Effect of epidural block combined with general anesthesia on c-fos and HSP70
      expression in the myocardium of spontaneous hypertensive rats].
AB  - OBJECTIVE: To study the efficacy of epidural block combined with general
      anesthesia on stress reaction in spontaneous hypertensive rats (SHR). METHODS:
      Eighteen SHR and 18 SD rats (above 24 weeks) were randomly divided into 6 groups,
      namely epidural block combined with general anesthesia group (A1,A2), general
      anesthesia group (B1,B2) and control group (D1,D2). General anesthesia was
      performed with celiac injection of droperidol, fentanyl and diazepam. Tracheal
      intubation and ventilation were performed after tracheotomy, and epidural block
      was conducted by incision. The rats in groups A1, A2, B1, B2 underwent
      splenectomy. All the rats were sacrificed 24 h after the surgery and two
      myocardium specimens were collected for detecting c-fos and HSP70 expression
      using RT-PCR. RESULTS: c-fos mRNA expression was significantly lower but HSP70
      mRNA expression significantly higher in group A1 than in group B1. CONCLUSION:
      Compared with general anesthesia, general anesthesia combined with epidural block
      can reduce the stress responses and protect cardiac myocytes by decreasing c-fos
      expression and increasing HSP70 expression in SHR.

PMID- 21097415
TI  - [Computed tomography and magnetic resonance imaging features of desmoid-type
      fibromatosis: comparison with the pathological findings].
AB  - OBJECTIVE: To explore the computed tomography (CT) and magnetic resonance imaging
      (MRI) features of desmoid-type fibromatosis, and improve the diagnostic accuracy
      and understanding of the disease. METHODS: The CT and MRI features of 18 cases of
      surgically and pathologically confirmed desmoid-type fibromatosis were reviewed
      retrospectively. Among the patients, 10 received CT pre- and post-contrast
      scanning, and 8 patients had MRI pre- and post-contrast scanning. The CT and MRI
      features were analyzed in comparison with the pathological findings. RESULTS: In
      the extra abdominal cases, the tumors occurred in the head and neck in 3, in the
      dorsal part of the chest in 2, in the abdominal wall and groin area in 9, and in
      the peritoneal cavity in 4; concomitant Gardner syndrome was found in 1 case. In
      4 cases the tumor occurred within 1 to 3 years after abdominal surgeries.
      Pathologically, the lesion was hard and composed of fusiform fibroblasts and
      myofibroblast. The cells showed no obvious heteromorphism with few karyokinesis,
      growing invasively and recurrent locally but without distant metastasis.
      Immunohistochemically, the fibroblasts and myofibroblasts expressed vimentin, and
      the myofibroblasts were positive for SMA. On CT and MRI, the lesion appeared
      benign with malignant growth pattern, and caused compression of the adjacent
      organs and vessels or encasement of the vessels; the border was unclear without
      encapsulation, and necrosis and calcification was scarce. The density and signal
      of the tumor were well distributed. Twelve patients displayed obvious enhancement
      and 5 showed uneven enhancement. CONCLUSION: The CT and MRI features of desmoid
      type fibromatosis are characteristic, and CT and MRI are valuable modalities for
      the diagnosis and differential diagnosis of the tumor.

PMID- 21097416
TI  - [Construction of pSG5/TRIF and its expression in Huh7 cells].
AB  - OBJECTIVE: To construct the plasmid pSG5/TRIF and investigate its expression in
      Huh7 cells. METHODS: The plasmid pCX4pur/Myc-TRIF was digested with Not I and the
      digestion product was blunted followed by further digestion with EcoR I to obtain
      the insert Myc-TRIF. pSG5 was digested sequentially with Sma I and EcoR I. All
      the digested products were analyzed with agarose gel electrophoresis. The
      products with the expected size were extracted and ligated, and the positive
      clones were screened by ampicillin and amplified. The recombinant pSG5/TRIF was
      extracted, purified, and identified by restriction endonuclease BamH I and
      agarose gel electrophoresis. The recombinant plasmids were transfected into Huh7
      cells with FuGene 6 reagents and into Huh7 cells previously infected with
      recombinant vaccinia virus (rVV) via Lipofectin. Immunofluorescence and Western
      blotting were performed to detect the expression of the recombinant plasmids, and
      the transfection efficiency with different transfection reagents was compared.
      RESULTS: BamH I digestion resulted in a fragment with the expected size.
      Immunofluorescence staining showed successful expression of Myc-TRIF protein in
      Huh7 cells, and the transfection efficiency was enhanced in Huh7 cells previously
      infected with rVV. SDS-PAGE analysis showed that the relative molecular mass of
      the expressed product by pSG5/Myc-TRIF was about 100 ku, and prior infection of
      the cells with rVV obviously increased transfection efficiency, as was consistent
      with the results of immunofluorescence. CONCLUSION: pSG5/Myc-TRIF is successfully
      constructed and expressed in Huh7 cells. The expression efficiency can be
      increased by prior infection of the cells with rVV.

PMID- 21097417
TI  - [Analysis of the factors related to glomerular filtration rate in type 2 diabetes
      without albuminuria].
AB  - OBJECTIVE: To analyze the risk factors affecting the glomerular filtration rate
      (GFR) in type 2 diabetic patients without albuminuria. METHODS: A total of 131
      type 2 diabetic patients with normal urinary albumin excretion rate (UAER) were
      divided into normal GFR group and decreased GFR group. The factors relevant to
      GFR were analyzed by multiple factors regression. RESULTS: Age, course of
      diabetes, systolic blood pressure, prevalence of hypertension, the level of serum
      creatinine (SCr), blood urea nitrogen (BUN) and uric acid (UA) were significantly
      higher in decreased GFR group than in normal GFR group. Multivariate regression
      showed that SCr, age, systolic blood pressure, and UA were negatively correlated
      to GFR. CONCLUSION: Reduced GFR occurs in some type 2 diabetic patients without
      albuminuria. SCr, age, systolic blood pressure and UA are the major factors
      related to decreased GFR. The degree of early renal damage in diabetic patients
      can be better evaluated by combining GFR and UAER.

PMID- 21097418
TI  - [Ultrasound-mediated microbubble cavitation enhances gene transduction in rat
      pulmonary endothelial cells partially by affecting membrane fluidity and
      cytoskeleton structure].
AB  - OBJECTIVE: To evaluate the effect of therapeutic ultrasound-induced microbubble's
      cavitation on plasmid gene transduction in rat pulmonary endothelial cells in
      relation to the changes of membrane fluidity and cytoskeleton structure. METHODS:
      Rat endothelial cells cultured in vitro were transfected with EGFP plasmid in the
      presence of protein microbubbles. During the transfection process, the cells were
      exposed to continuous 2 MHz ultrasonic irradiation for 30, 60, 90, 120 and 180 s
      (groups A, B, C, D and E, respectively) with the constant mechanical index (MI)
      of 1.0, or for 60 s with different mechanical index (MI) of 0.5, 0.75, 1.0, 1.5,
      and 1.8 (groups B1, B2, B3, B4 and B5, respectively). The changes of endothelial
      cytoskeletal structure and membrane fluidity were evaluated by immunofluorescence
      staining after the exposure. RESULTS: EGFP gene transduction increase obviously
      with prolonged echo irradiation and increased MI. The intensity of
      immunofluorescence staining, which represented endothelial membrane fluidity, was
      0.173+/-0.013, 0.250+/-0.037, 0.364+/-0.022, 0.381+/-0.019, and 0.395+/-0.009 in
      groups A-E, as compared with 0.171+/-0.017, 0.255+/-0.026, 0.378+/-0.007, 0.382+/
      0.009 and 0.397+/-0.008 in groups B1-B5, respectively. The recovery intensity of
      the immunofluorescence staining representing the changes in microtubulin of the
      cytoskeleton structure was 159.15+/-4.79, 188.23+/-6.20, 205.80+/-4.48, 208.99+/
      8.34, and 213.70+/-5.09 in groups A-E, and was 176.84+/-3.10, 187.57+/-14.52,
      206.41+/-11.66, 220.12+/-13.39 and 221.16+/-12.78 in groups B1-B5, respectively.
      The endothelial membrane fluidity and microtubule fluorescence recovery intensity
      increased remarkably compared with the baseline (P<0.01) within the MI range of
      0.50-1.0 and the exposure time of 30-90 s, but underwent no further changes in
      response to prolonged exposure time (180 s) at the MI of 1.5 (P>0.05). No changes
      in microfilament fluorescence intensity were observed after exposure to different
      MI or irradiation time. CONCLUSION: Therapeutic ultrasound-mediated albumin
      microbubble cavitation allows enhances plasmid gene transduction without causing
      cytoskeleton damages. Increased endothelial membrane fluidity and changes in
      cytoskeleton structure, especially microtubulin, partially contribute to this
      enhancement.

PMID- 21097419
TI  - [Prognostic analysis of partial atrium or large blood vessel resection for
      treatment of locally advanced lung cancer].
AB  - OBJECTIVE: To explore the value of partial atrium or large blood vessel resection
      for the treatment of locally advanced lung cancer. METHODS: Thirty-five patients
      with locally advanced lung cancer (T(4)N(0)-N(2)M(0)) underwent lobectomy or
      pneumonectomy combined with intrapericardial vascular management or partial
      resection of the atrium. Of the 35 patients , 15 underwent left pneumonectomy
      combined with partial resection of the left atrium, 3 had pneumonectomy and
      partial resection of pulmonary artery trunk, 11 received right pneumonectomy and
      partial resection of the left atrium, 3 had middle and lower lobectomies and
      partial resection of the left atrium, and 3 underwent right upper lobectomy,
      partial resection of the superior vena cava and replacement of artificial blood
      vessel. RESULTS: No death occurred in the 35 patients. Postoperative arrhythmia
      occurred in 4 cases and respiratory failure in 2 cases. The 1, 2, 3 and 4 year
      survival rates of the patients were 79.2% (19/24), 53.3% (8/15), 46.2% (6/13) and
      36.4% (4/11), respectively. Pathologically, 27 patients had squamous carcinoma, 3
      had adenocarcinoma, 3 had adenosquamous carcinoma and 2 had large cell carcinoma.
      In TNM staging, 6 were in T(4)N(0)M(0), 11 in T(4)N(1)M(0) and 18 in
      T(4)N(2)M(0). CONCLUSION: Pneumonectomy or lobectomy combined with
      intrapericardial vascular management or partial resection of the atrium can
      enhance the possibility of radical resection of locally advanced lung cancer and
      increase the long term survival rate.

PMID- 21097420
TI  - [Comparison of single intubating dose and continuous infusion of rocuronium in
      prolonged gynecologic laparoscopic surgery].
AB  - OBJECTIVE: To compare the cardiorespiratory factors and surgical conditions
      during total intravenous anesthesia for prolonged laparoscopic pelvic surgery
      with or without supplemental muscle relaxants. METHODS: Forty female ASA I or II
      patients undergoing laparoscopic pelvic surgeries were randomized into two groups
      A and B, both with standardized anesthesia via a intravenous bolus injection of
      rocuronium (0.6 mg/kg). The patients in group B received continuous rocuronium
      infusion upon observation of one TOF twitch response with the T1 value maintained
      within 0-10% and rocuronium withdrawal at 20 to 30 min before the completion of
      the surgery. The patients in group A received no supplemental muscle relaxants.
      The cardiorespiratory parameters were measured during the operation. The
      respiratory system compliance (Ceff rs) was calculated as the quotient of the
      tidal volume (VT) and peak inspiratory pressure (PIP), and the operative
      conditions were graded by the operating gynecologist. RESULTS: The
      cardiorespiratory parameters significant increased and Ceff rs decreased after
      pneumoperitoneum, but no significant differences were found between the two
      groups. The surgical conditions were also comparable between the two groups, but
      the duration of intubation and the operating time were significantly shorter in
      the group A. CONCLUSION: Pneumoperitoneum severely affects the cardiorespiratory
      parameters during laparoscopy, which can not be lessened by neuromuscular block
      agents. A single intubating dose of rocuronium can suffice the requirement of
      prolonged gynecologic laparoscopic surgery.

PMID- 21097421
TI  - [Clinical value of multi-tumor markers protein biochip in the diagnosis of
      pulmonary carcinoma].
AB  - OBJECTIVE: To assess the value of multi-tumor markers protein biochip in the
      diagnosis and therapy of pulmonary carcinoma. METHODS: Twelve tumor markers
      (CA199, NSE, CEA, CA242, Ferrtin, beta-HCG, AFP, f-PSA, PSA, CA125, HGH, and
      CA153) were detected using protein chip in 308 patients with pulmonary carcinoma,
      218 with benign lung lesions and 250 healthy subjects. RESULTS: The positivity
      rate was 72.4% in pulmonary carcinoma cases, obviously higher than that in the
      benign cases (22.0%, P<0.01) and healthy subjects (5.6%, P<0.01). The positivity
      rates differed significantly between the pulmonary carcinoma cases of different
      pathological types. The positivity rates of CEA, CA125, and CA153 were
      significantly higher in adenocarcinoma cases than in squamous carcinoma cases
      (P<0.05), and also higher in cases with lymph node metastasis than in those
      without (71.9% vs 52.1%, P<0.05). CONCLUSION: Protein biochip containing multiple
      tumor markers provides valuable assistance in the diagnosis and therapeutic
      effect monitoring of pulmonary carcinoma.

PMID- 21097422
TI  - [Clinical study of blood type A donor liver transplantation in type O
      recipients].
AB  - OBJECTIVE: To study the clinical effect and feasibility of blood type A donor
      liver transplantation in blood type O recipients. METHODS: The clinical data were
      analyzed in 6 blood type O patients receiving transplantation of the liver grafts
      from blood type A donors. The clinical effect and outcomes of the
      transplantations were evaluated to assess the feasibility of ABO incompatible
      liver transplantation between type A donors and type O recipients. RESULTS: The
      operations and the postoperative recovery were smooth in all the 6 recipients.
      Only one patient died 5 months postoperatively due to liver tumor metastasis, and
      the other 5 patients survived with the longest survival reaching 14 months. Acute
      graft rejection occurred in one patient 1 week after the operation on account of
      abnormally elevated serum bilirubin level, which was successfully managed with
      immediate methylprednisolone therapy. No such complications as acute graft
      rejection, bile duct stenosis or bile leakage was found in the other patients.
      CONCLUSION: Blood type A donor liver transplantation in type O recipient is
      feasible in emergency or other special conditions.

PMID- 21097423
TI  - [Correlation of ABO groups to hypertensive intracerebral hemorrhage].
AB  - OBJECTIVE: To study the relationship between ABO blood groups and hypertensive
      intracerebral hemorrhage (HICH). METHODS: The clinical data of 425 patients with
      HICH admitted to Nanfang Hospital were collected to analyze the relationship
      between the ABO blood groups and the occurrence of HICH, with normal Han Chinese
      subjects serving as the controls. RESULTS: Compared to the officially documented
      distribution of ABO groups in Chinese population (O 34.11%, B 28.98%, A 28.29%,
      AB 8.69%) and in Guangzhou residents (O 46.00%, B 25.00%, A 23.00%, AB 6.00%), a
      significant difference was noted in the blood group distribution in this cohort
      (O 45.10%, A 26.00%, B 24.00%, AB 4.90%). O blood type individuals with HICH
      showed a higher morbidity than others. Th ABO blood type distribution in this
      cohort showed no significant difference from that in the control group (P>0.05),
      but differed significantly from the Chinese norm (P<0.05). CONCLUSION: The ABO
      blood group is a factor contributing to the occurrence of HICH. O blood type is
      related to cerebral hemorrhage, and may serve as a risk factor for HICH.

PMID- 21097424
TI  - [Effect of percutaneous intratumoral injection of lipiodol emulsion of
      chemotherapie agents on implanted VX2 tumor in rabbits].
AB  - OBJECTIVE: To assess the therapeutic effect of percutaneous intratumoral
      injection with lipiodol emulsion of chemotherapie agents (CALE) on implanted VX2
      tumor in rabbits. METHODS: Twelve New Zealand rabbits with implanted VX2 tumor
      (24 models) were divided into lipiodol group, chemotherapeutic agent group and
      CALE group with intratumoral injections of the corresponding agents. The
      pathological changes of all the lesions were observed and the expression of
      proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor
      (VEGF) were evaluated 7 days after the operation. RESULTS: Compared with the
      lipiodol group and chemotherapie agent group, intratumoral injection of CALE
      resulted in the highest tumor necrosis rate and greatest tumor necrosis (P<0.01).
      The labeling indices of PCNA and VEGF expressions in CALE group were markedly
      lower than those in the other two groups (P<0.01). CONCLUSION: Percutaneous
      intratumoral injection of CALE is an effective ablation approach for treatment of
      malignant solid tumors.

PMID- 21097425
TI  - [Proliferation of tissue-engineered cartilage cells under compressive stress].
AB  - OBJECTIVE: To investigate the proliferation of tissue-engineered cartilage cells
      stimulated by different intensities of compressive stress. METHODS: Human
      embryonic cartilage cells were seeded into type II collagen sponge scaffold. The
      cells of the pressure groups were stimulated by different compression rate (0-5%,
      0-10%, and 0-20%) at a cyclical frequency of 0.1 Hz. The cells of the control
      group were cultured without pressure. Gross observation, histological section,
      MTT assay and flow cytometry were used to observe the morphology, cell number and
      distribution and detect the cell proliferation and cell cycle. RESULTS: Tissue
      engineered cartilage cells in 0-10% group showed the largest size and greatest
      thickness with normal morphology. Tissue biopsies showed the largest number of
      cartilage cells with more uniform distribution, close alignment, more matrix
      secretion. The cartilage cell activity was significantly enhanced and the
      percentage of S phase cells significantly increased in the pressure group
      compared with those in the control group, and such changes were especially
      obvious in 0-10% group in which the S phase cells increased by 59.0% compared
      with that in the control group. CONCLUSION: The proliferation of tissue
      engineered cartilage cells is regulated by the cyclic stress intensity, and a
      pressure frequency of 0.1 Hz with compression rate of 0-10% can better promote
      the cell proliferation.

PMID- 21097426
TI  - [An optimized method for extracting corosolic acid from loquat leaves].
AB  - OBJECTIVE: To extract corosolic acid from loquat leaves for medical use. METHODS:
      Loquat leaves were boiled in water to remove the water-soluble substances
      followed by 3 cycles of extraction with 25% aqueous methanol for 30 min and then
      by 95% aqueous methanol for 1 h at 80 degrees celsius;. After cooling at room
      temperature and filtration, the extract was treated with activated carbon to
      remove chlorophyll, and the liquid was filtered and concentrated to allow
      precipitation. The sediment was washed to obtain the total crude triterpene acid,
      which was further dissolved with methanol and purified by high-performance liquid
      chromatography (HPLC). The fractions including corosolic acid were collected,
      concentrated with vacuum distillation, and dried to obtain corosolic acid
      product, which was analyzed with HPLC. RESULTS: HPLC analysis of the extracts
      showed that the percentages of corosolic acid were 4.66%, 2.42%, and 24.18% in
      crude corosolic acid extracted with methanol, boiling water, and 95% aqueous
      methanol, respectively. After purification with HPLC, the purity of corosolic
      acid in the product exceeded over 80%. CONCLUSION: The optimal extraction method,
      which is convenient and cost-effective, is established for extracting corosolic
      acid from loquat leaves for medical use.

PMID- 21097427
TI  - [Diagnosis of mucinous cystadenoma of the appendix by ultrasound and analysis of
      the misdiagnosed cases].
AB  - OBJECTIVE: To explore the ultrasound characteristics of mucinous cystadenoma of
      the appendix and evaluate its diagnostic value. METHODS: Fourteen cases of
      mucinous cystadenoma of the appendix were diagnosed by ultrasonic examination and
      confirmed by surgery and pathology. The ultrasound findings and distribution of
      color Doppler flow signals were observed and analyzed in comparison with the
      surgical and pathological results. RESULTS: Ultrasound revealed a unilocular or
      multilocular cystic mass located in the right lower quadrant area with clear
      boarders, smooth and thick wall, and inconsistent internal echogenicity. The
      maximal outer diameter of the mass was 2 cm or greater in attachment to the
      cecum, lacking of periileal inflammatory changes such as in the periileal lymph
      nodes and echogenic periappendiceal epiploon. CONCLUSION: Ultrasound is of high
      value in the diagnosis of mucinous cystadenoma of the appendix.

PMID- 21097428
TI  - [Preparation of immunomagnetic nanoparticles for tumor targeting therapy with
      herceptin].
AB  - OBJECTIVE: To prepare immunomagnetic nanoparticles (IMNs) for HER2/neu-targeted
      radioimmunotherapy with herceptin, a humanized anti-p185-HER-2/neu monoclonal
      antibody targeting the extracellular domain of HER-2/neu receptor. METHODS: The
      magnetic nanoparticles were synthesized by partial reductive precipitation method
      and the surface of the particles was chemically modified using silane coupling
      agent. Herceptin and histidine were covalently linked to the amine group upon the
      silica-coated magnetic nanoparticles modified by N-[3-(trimethoxysilyl) propyl]
      ethylenediamine using glutaraldehyde method to prepare the IMNs. The
      nanoparticles were evaluated by diffraction (XRD), scanning electron microscope
      (SEM) and X- ray energy spectrometry (EDS), and the immunoreactivity of IMN was
      determined. RESULTS: The average diameter of the decanoic acid-coated Fe(3)O(4)
      nanoparticle was about 20 nm with a magnetic saturation of 65 emu/g. The surface
      amino group was 0.5 umol/mg after modification with the amid functional group,
      and the mean size of Herceptin-loaded IMNs was about 60 nm. The IMN retained good
      immunoreactivity of Herceptin. CONCLUSION: The IMNs exhibit good properties for
      potential application in tumor targeting therapy using Herceptin against HER
      2/nue proto-oncogene.

PMID- 21097429
TI  - [Pectoralis major myocutaneous flap for repairing large tissue defects following
      oral cancer surgery].
AB  - OBJECTIVE: To investigate the method for reconstruction of large tissue defects
      following surgical resection of advanced oral cancer using pectoralis major
      myocutaneous flap. METHODS: From 2005 to 2009, 40 patients with advanced oral
      cancer received extensive surgical resection of oral cancer, and the intraoral
      defects were reconstructed using pectoralis major myocutaneous flaps. RESULTS:
      All the flaps survived except one flap with partial necrosis. CONCLUSION:
      Pectoralis major myocutaneous flap is effective for reconstruction of large
      tissue defects after resection of advanced oral cancer.

PMID- 21097430
TI  - [Relationship between early spontaneous cardioversion of atrial fibrillation and
      thyroid hormone metabolism after mitral replacement in patients with rheumatic
      heart disease].
AB  - OBJECTIVE: To analyze the relationship between early spontaneous cardioversion of
      atrial fibrillation (AF) and thyroid hormone metabolism after mitral replacement
      in patients with rheumatic heart disease, and explore the treatment strategy of
      early spontaneous cardioversion after mitral valve replacement. METHODS:
      According to the occurrence of cardioversion, 138 patients with mitral valve
      replacement were divided into conversion group and non-conversion group, and
      based on the duration of sinus rhythm, the patients in conversion group were
      divided into < 3 days group and > 3 days group. Triiodothyronine (T3) was
      detected by radioimmunoassay in all the patients. RESULTS: T3 metabolism
      decreased significantly after the operation in all the patients. Early
      spontaneous cardioversion of AF occurred 2 h after the operation in 52 cases
      (37.7%), and 28 (20.3%) of the cases had a duration of sinus rhythm longer than 3
      days. T3 was significantly decreased in conversion group and non-conversion group
      by 44.5% and 58.7% at 2 h, by 40.0% and 52.4% at 24 h and by 28.6% and 37.7% at
      72 h after the operation, respectively. The levels of T3 in conversion group was
      significantly higher than the levels in non-conversion group, and showed no
      significant variation with the duration of sinus rhythm. CONCLUSION: Enhancement
      of T3 levels after mitral valve replacement may increase the probability of early
      spontaneous cardioversion of AF, but can not affect the duration of sinus rhythm.
      This finding supports the supplementation of T3 perioperatively in patients
      undergoing cardiac surgeries.

PMID- 21097431
TI  - [Changes in serum electrolyte levels after seawater immersion of open abdominal
      wound and drowning in dogs].
AB  - OBJECTIVE: To assess the effects of seawater immersion of open abdominal wound
      and drowning on plasma electrolyte levels in dogs. METHODS: Twenty-one dogs with
      open abdominal wounds were randomly divided into 3 groups, namely the control
      group (n=7), seawater immersion group (n=7) and seawater immersion and drowning
      group (n=7). The dogs in the control group were subjected to simple open
      abdominal wound, and those in the latter two groups were immersed into seawater
      after the abdominal injury. The changes in the plasma electrolytes and osmotic
      pressure were observed after the treatments. RESULTS AMD CONCLUSION: Seawater
      immersion of the open abdominal wound results in hypematremia, hyperkalemia and
      hypertonic dehydration, and the effect is proportional to the length of immersion
      time, but seawater airway perfusion does not cause obvious changes of the plasma
      electrolytes and osmotic pressure in dogs.

PMID- 21097432
TI  - [Minimally invasive percutaneous plate osteosynthesis for treatment of proximal
      humerus fractures with PHILOS plate].
AB  - OBJECTIVE: To investigate the effect of minimally invasive percutaneous plate
      osteosynthesis (MIPPO) for treatment of proximal humerus fractures with PHILOS
      plate. METHODS: From January 2008 to July 2009, 22 cases of proximal humerus
      fractures were treated with MIPPO with PHILOS plate. According to Neer
      classification, 7 cases had two-part fractures, 12 had three-part fractures, and
      3 had four-part fractures. RESULTS: All the 22 cases were followed up ranging
      from 6 to 12 months with an average of 10 months. The functional results of the
      shoulder, according to Neer scores, were classified as excellent in 9 cases, good
      in 10 cases and fair in 3 cases, with an average score was 86.4%. CONCLUSION:
      PHILOS using MIPPO shows good results for treating proximal humerus fractures.

PMID- 21097433
TI  - [Preemptive analgesic effect of parecoxib sodium in patients undergoing
      laparoscopic colorectal surgery].
AB  - OBJECTIVE: To investigate the preemptive analgesic efficiency of parecoxib in
      patients undergoing laparoscopic colorectal surgery. METHODS: Forty ASA I-II
      patients aged 30 to 64 years undergoing laparoscopic colorectal surgery were
      randomized to receive either intravenous parecoxib sodium (40 mg) at anesthesia
      induction (group A) or intravenous parecoxib sodium (40 mg) 30 min before the
      completion of surgery (group B). Butorphanol was administered by patient
      controlled analgesia for postoperative analgesia. The intensity of pain measured
      by VAS score was recorded at 2, 4, 6, 8, 12, and 24 h after the operation. The
      number of unsatisfied demand and the number of successfully delivered doses,
      butorphanol consumption at 12 h and 24 h after the operation, the patients'
      global evaluation of the postoperative analgesia and the number of the patients
      receiving rescue medication and adverse effects related to analgesia were
      recorded and compared between the two groups. RESULTS: The VAS scores at
      different time points were significantly lower in group A than in group B
      (P<0.05). The number of unsatisfied demand and the number of successfully
      delivered doses were significantly higher and butorphanol consumption at 12 h and
      24 h after the operation was significantly less in group A (P<0.05). The
      incidence of adverse events was similar between the two groups. CONCLUSION:
      Administration of 40 mg parecoxib sodium at anesthesia induction in the patients
      undergoing laparoscopic colorectal surgery can result in significant preemptive
      analgesia.

PMID- 21097434
TI  - [Effect of cerebral state index as a measure of depth of sedation during target
      controlled infusion of propofol in patients of different ages].
AB  - OBJECTIVE: To investigate the effect of cerebral state index (CSI) in measuring
      the level of sedation during target controlled infusion (TCI) of propofol in
      patients of different ages. METHODS: Forty ASA class I-II patients undergoing
      general anesthesia were divided into group A (65 to 79 years old, n=20) and group
      B (20 to 55 years, n=20). The sedation level was assessed using OAA/S scale.
      Anesthesia was induced with TCI of propofol. The target effect-site concentration
      (CE) was set initially at 0.5 ug/ml followed by increments of 0.5 ug/ml every 5
      min until 5 min after the patients lost consciousness and did not respond to pain
      stimulation (OAA/S=0). OAA/S score was recorded every 20 s, and MAP, HR, SPO(2)
      and CSI were recorded. Spearman correlation coefficient between OAA/S score and
      CSI and their prediction probabilities (Pk) were calculated. The values of
      CE(05), CE(50), CE(95) and CSI(05), CSI(50), CSI(95) at loss of verbal contact
      (LVC) (OAA/S=2) and loss of consciousness (LOC) (OAA/s<=1) were also calculated.
      RESULTS: CSI was well correlated to the sedation depth. The values of CE(50) and
      CSI50 were 1.3 ug/ml and 69.7 at LVC in group A, and were 1.8 ug/ml and 65.9 at
      LVC in group B, respectively. The values of CE(50) and CSI(50) were 1.5 ug/ml and
      64.3 at LOC in group A, as compared to 2.5 ug/ml and 54.8 at LOC in group B,
      respectively. When the OAA/S scale was lower than 3, the CSI values in group A
      were significantly higher than those in group B (P<0.05). CONCLUSION: CSI can
      effectively and rapidly distinguish the level of sedation in different age
      groups. At the same OAA/S scale, the target effect-site concentration in the
      elderly is obviously lower than that in the young patients, but CSI values were
      significantly higher in the elderly than in the young patients during TCI of
      propofol.

PMID- 21097435
TI  - [Retroperitoneal laparoscopic surgery combined with ureteroscopic lithotomy for
      treatment of renal and ureteral calculi].
AB  - OBJECTIVE: To evaluate the feasibility of retroperitoneal laparoscopic surgery
      combined with ureteroscopic lithotomy through the pelvis for treatment of renal
      and ureteral calculi. METHODS: In February 2010, 2 patients with renal and
      ureteral calculi underwent retroperitoneal laparoscopic surgery combined with
      ureteroscopic lithotomy through the pelvis. RESULTS: The operation time in these
      two cases was 70 and 80 min, and the volume of intraoperative blood loss was
      about 20 ml. The exposure was excellent, and the patient recovered rapidly
      without complications or residual calculi. CONCLUSION: Retroperitoneal
      laparoscopic surgery combined with ureteroscopic lithotomy through the pelvis is
      feasible for treatment of renal and ureteral calculi.

PMID- 21097436
TI  - [High-performance liquid chromatography for determination of psoralene, bergapten
      and apigenin in Ficus hirta Vahl].
AB  - OBJECTIVE: To establish a high-performance liquid chromatography (HPLC)-based
      method for determining the contents of psoralene, bergapten and apigenin in Ficus
      hirta Vahl. METHODS: A Hypersil C18 column (250 mm * 4.6 mm, 5 um) was used with
      the mobile phase of methanol-water (60:40), flow rate of 1.0 ml/min, detection
      wavelength of 268.7 nm and column temperature of 30 degrees celsius. RESULTS: The
      calibration curve was linear within the range of 10.0-30.0 ug/ml for psoralene
      (r=0.9998), 15.0-45.0 ug/ml for bergapten (r=0.9998) and 5.0-15.0 ug/ml for
      apigenin (r=0.9992). The average recovery of psoralene was 99.7% (RSD=1.99%),
      that of bergapten was 99.9% (RSD=1.71%) and that of apigenin was 100.3%
      (RSD=1.78%). CONCLUSION: The method is simple, economic and accurate with good
      reproducibility for the contents of psoralene, bergapten and apigenin.

PMID- 21097437
TI  - [Weekly irinotecan plus capecitabine as a second-line chemotherapy for advanced
      gastric cancer: an analysis of 21 cases].
AB  - OBJECTIVE: To evaluate the efficacy and adverse effects of weekly irinotecan
      combined with capecitabine as a second-line chemotherapy for treatment of
      advanced gastric cancer. METHODS: Twenty-one patients with advanced gastric
      cancer who had failed first-line therapy received irinotecan on days 1 and 8 plus
      capecitabine on days 1-14 for a 21-day cycle. Each patient was treated for at
      least two cycles and evaluated 4 weeks later for the responses. RESULTS: Of the
      21 patients, none showed complete remission (CR), 5 (23.8%) showed partial
      remission (PR), 6 (28.6%) showed stable disease (SD) and 10 (47.6%) showed
      progressive disease (PD). The overall response rate was 23.8%, and 11 patients
      (52.4%) benefited (CR+PR+SD) from the clinical therapy, with a mean time to tumor
      progression of 3.61+/-0.97 months. The main adverse effects of this regimen
      included myelosuppression, nausea, vomiting and diarrhea. CONCLUSION: The regimen
      of weekly irinotecan plus capecitabine has a definite effect for treatment of
      advanced gastric cancer with tolerable toxicity.

PMID- 21097438
TI  - [Efficacy and safety of amiodarone and metoprolol in the treatment of ventricular
      premature beats: a meta-analysis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of amiodarone and metoprolol in
      the treatment of ventricular premature beats. METHODS: Controlled randomized
      clinical trials from 1999 through 2009 were retrieved in China HowNet, VIP Web,
      Pubmed home. Using Rev Man4.2 software provided by Cochrane Collaboration, Meta
      analysis was conducted of 30 articles meeting the inclusion criteria involving a
      total of 1188 patients. RESULTS: Merged analysis of amiodarone and metoprolol in
      the treatment of premature ventricular merge showed a comprehensive test results
      of Z=1.25, P=0.21, OR=1.18, 95%CI: 0.91-1.54; funnel plot analysis suggested the
      possible presence of publication bias. The comprehensive test of the incidence of
      adverse reactions in relation to the two drugs resulted in an OR of 1.96 (95%CI:
      1.39-2.77), and funnel plot analysis also indicated publication bias.
      CONCLUSIONS: The total response rate of amiodarone does not seem to be superior
      to metoprolol in the treatment of premature ventricular contractions, and
      amiodarone is associated with higher incidence of adverse reactions.

PMID- 21097439
TI  - [Effect of varying lingual traction forces on the space-closing speed in a
      typodont model].
AB  - OBJECTIVE: To investigate the influences of varying lingual traction forces on
      the space-closing speed in a typodont model. METHODS: Forty-two Angle Class I
      standard typodont models of bimaxillary teeth protrusion were divided into 7
      equal groups. Four regions of the model were paired to groups, and in the odd
      numbered models, the top left and bottom left regions served as the experimental
      group and the top right and bottom right regions as the control group; in the
      even-numbered models, the regions in the model were grouped oppositely. In the
      experimental group, the space was closed by niti wire extension spring in the
      buccal ridge combined with lingual elastic traction of 0, 5, 10, 15, 20, 25 and
      30 g. In the control group, the space was closed by exclusive niti wire extension
      spring in the buccal ridge. The space-closing speed were analyzed in all the
      groups. RESULTS: The space-closing speed was significantly lower in the control
      group than in the experimental groups with lingual traction forces of 5, 10, 15,
      20 and 25 g (P<0.05), but a traction force of 30 g resulted in a significantly
      lower speed than that in the control group (P<0.05). The space closing speed was
      the greatest in the experimental group with a traction force of 15 g (P<0.05).
      CONCLUSION: Niti wire extension spring in the buccal ridge combined with lingual
      elastic traction results in faster space-closing speed than traditional exclusive
      niti wire extension spring. The speed is the fastest by applying 15 g lingual
      traction, which is also associated with the lowest slip resistance.

PMID- 21097440
TI  - [Effect of plasmaslyte A on the liver function of patients undergoing cardiac
      surgery with extracorporeal circulation].
AB  - OBJECTIVE: To observe the effect of plasmaslyte A on the liver function of
      patients receiving cardiac surgery with extracorporeal circulation. METHODS:
      Sixty patients scheduled for cardiac surgery were randomized to receive
      plasmaslyte A (group P, n=30) and ringer lactate solution (group R, n=30). The
      two agents were used in priming heart-lung machine and intra- and postoperative
      crystal solution. All the patients were examined for the levels of AST, ALT and
      Lac the day before and at 2 h and 1, 3 and 7 days after the surgery. The time of
      extubation and length of stay at the ICU were record. RESULTS: The levels of ALT,
      AST and Lac in group P were significantly lower than those in group R (P<0.05),
      and the duration of intubation and stay at the ICU was shorter in group P
      (P<0.05). CONCLUSION: Plasmaslyte A can markedly reduce the level of AST, ALT and
      Lac and protect the liver function of patients undergoing cardiac surgery with
      extracorporeal circulation.

PMID- 21097441
TI  - [Cytogenetic study of Down syndrome cases in southern Hainan Province and report
      of a rare case of abnormal karyotype].
AB  - OBJECTIVE: To investigate the distribution and characteristic of the karyotypes
      in Down syndrome (DS) patients in southern Hainan Province, China. METHODS:
      Cytogenetic analysis was carried out in 132 cases clinically suspected of DS.
      RESULTS: Eighty-six of the cases were diagnosed as DS with karyotype analysis.
      Among the DS patients in southern Hainan, 93.02% of the cases had typical trisomy
      21, 3.49% had translocation, and 3.49% had mosaic karyotype. The percentage of DS
      babies born by younger mothers (<35 years) was greater than that of the babies
      born by elder mothers (91.86% vs 8.14%). In addition, a case of translocation
      between chromosomes 5 and 8 with regular trisomy 21 was identified, which
      represented the first case ever reported. CONCLUSION: Typical trisomy 21
      karyotype is more frequent in DS cases than translocation and mosaic karyotypes
      in southern Hainan Province, where the mother delivering a child with DS tends to
      be younger.

PMID- 21097442
TI  - Correlation of Ki-67 and MCM-2 proliferative marker expression with grade of
      histological malignancy (G) in ductal breast cancers.
AB  - The study aimed at examining a relationship between expression of Ki-67 antigen
      and minichromosome maintenance 2 protein (MCM-2) and a grade of histological
      malignancy G in ductal breast cancers. The function of widely used marker of
      proliferation Ki-67 is still not clear. In contrast, the MCM-2 protein is well
      known to play an important role in controlling the cell cycle. Both proteins
      represent small protein molecules, which manifest nuclear expression only during
      cell division of normal and neoplastic cells. Their expression is noted in
      several malignant tumours. These studies were conducted on 56 archival paraffin
      blocks of ductal breast cancers. Immunohistochemical reactions were performed
      using monoclonal Ki-67- and MCM-2-specific antibodies. Statistical analysis
      demonstrated a positive correlation between expressions of two proteins (r=0.6;
      p<0.05). The most intense expression of these two markers was demonstrated in G3
      grade cancers. Statistical analysis showed more pronounced expression of Ki-67
      antigen in G3 grade cancers as compared to cancers of G1 and G2 grades (p<0.001)
      and, in the case of MCM-2 protein, a more pronounced expression in G3 grade
      cancers, as compared to those of G1 (p<0.05) or G2 grade (p<0.01). The results
      obtained in our study suggest that MCM-2 could be used as a marker of
      proliferation in breast carcinomas.

PMID- 21097444
TI  - Evaluation of the influence of ozonotherapy on the clinical parameters and MMP
      levels in patients with chronic and aggressive periodontitis.
AB  - PURPOSE: A comparison of the clinical status and salivary MMP levels after SRP
      alone or with ozonotherapy in patients with aggressive and chronic periodontitis.
      MATERIAL/METHODS: The study was performed in 52 generally healthy subjects with
      chronic or aggressive periodontitis. Group CP-S consisted of 12 patients with
      chronic periodontitis, who underwent scaling and root planing (SRP). In group CP
      O there were 25 patients with chronic periodontitis who additionaly to SRP
      underwent ozonotherapy. The same therapy was performed in group AP, containing 15
      patients with aggressive periodontitis. Plaque index, approximal plaque index,
      bleeding on probing, sulcus bleeding index, probing pocket depth and clinical
      attachment loss were measured at baseline, at two weeks and two months post
      therapy. The levels of MMP-1, MMP-8 and MMP-9 were estimated in non-stimulated
      saliva with an ELISA method. RESULTS: All the clinical parameters assessed in the
      study groups were reduced after treatment. SRP with additional ozonotherapy
      provided an increase in MMP levels in patients with chronic periodontitis and a
      reduction in MMP levels in patients with aggressive periodontitis. CONCLUSIONS:
      SRP followed by ozonotherapy does not lead to further improvement in clinical
      periodontal parameters in patients with AP and CP.

PMID- 21097443
TI  - Evaluation of peroxidase activity by alpha-naphthol/pyronine staining compared
      with benzidine staining in 101 acute leukemia cases.
AB  - Cytochemical detection of myeloperoxidase (MPO) activity, a strong marker for
      myeloid differentiation, is usually performed by benzidine dihydrochloride
      staining, with the threshold at 3%. Several reports have demonstrated the
      potential toxicity of benzidine, and bans have been issued, under French law,
      prohibiting female technicians from being exposed to the aromatic hydrocarbon
      group, including benzidine. The aim of this study was to test an alpha-naphthol
      and pyronine-based substitute using a standardized kit (MYELOPEROXIDASE KIT, RAL
      [Reactifs RAL, Martillac, France]) to measure MPO activity in blast cells. This
      prospective, multicenter study made it possible to analyze 101 acute leukemia
      (AL) cases; it has also demonstrated both the 96% specificity and the 99%
      sensitivity of the method, with a threshold for positive staining of 3%, as well
      as good correlation (r = 0.95) between the staining method tested and the
      benzidine staining method. When using the alpha-naphthol/pyronine-based staining
      for MPO, the mean number of positive blast cells is statistically lower than that
      obtained using benzidine, but without incidence on AL classification. These
      results allow us to conclude that this method makes it possible to classify acute
      blood diseases by measuring MPO activity using reagents permitted by law,
      according to a standardized and reproducible protocol.

PMID- 21097445
TI  - Long-term weight gain and metabolic syndrome, adiponectin and C-reactive protein
      in women aged 50-60 years.
AB  - PURPOSE: The aim of this study was to determine the impact of the weight change
      during 30-40 year follow-up on the prevalence of metabolic syndrome (MS)
      components, C-reactive protein (CRP) and adiponectin. MATERIAL AND METHODS: The
      study included 153 women. Blood pressure, anthropometric and laboratory measures
      were done at the age of 50-60 years. All women declared normal body weight at age
      20. The MS was defined according to the International Diabetes Federation (IDF
      2005). Women were divided into four groups according to weight gain: < 10 kg, 10
      19 kg, 20-29 kg, > 30 kg. RESULTS: The highest values of waist circumference,
      BMI, WHR, CRP, glucose, HOMA index, insulin, triglycerides, blood pressure and
      the lowest concentrations of adiponectin and HDL-cholesterol were observed in the
      group with the highest weight gain (above 30 kg). Odds ratio for MS was tenfold
      higher in group with weight gain 10-19 kg and 20-29 kg and twenty fold higher in
      group with weight gain above 30 kg. In multiple regression analysis CRP was most
      significantly correlated with weight gain. CONCLUSIONS: Among biochemical
      parameters of metabolic syndrome CRP seems to be the most significantly related
      to weight gain. The risk of metabolic syndrome is significantly increased even
      when the weight gain is 10 kg in middle-aged women characterized by a normal BMI
      at the age of 20.

PMID- 21097446
TI  - Outcome and treatment strategy in female lung cancer: a single institution
      experience.
AB  - PURPOSE: To assess the survival rate of female lung cancer treated at the
      Institute of Oncology of the Vilnius University, Lithuania during the period
      between 1996-2005. MATERIALS AND METHODS: During the period between 1996-2005,
      471 women diagnosed with lung cancer were treated at the Department of Thoracic
      Surgery and Oncology of the Institute of Oncology, Vilnius University. Data on
      morphology, stage and treatment was collected from the medical records. All lung
      cancer cases by histology were classified in two groups: non-small cell lung
      cancer (includes squamous cell carcinoma, large cell carcinoma, adenocarcinoma
      and other less common types) and small cell lung cancer. The vital status of the
      study group was assessed as of December 31, 2007, by passive follow-up, using
      data from the population registry. It was found that 411 (87.3%) of the patients
      had died. Survival was estimated according to the Kaplan-Meier method. RESULTS:
      The median survival of female lung cancer diagnosed during 1996-2005 in Lithuania
      show to be 8.7 months (8.4 (95% CI 7.2-10.8) months with non-small cell lung
      cancer and 9.3 (95% CI 6.3-13.0) months with small-cell lung cancer). Survival
      was more than 20 months in resectable non-small cell lung cancer (stages I, II,
      IIIA). Non-small cell lung cancer survival in advanced stages was less than 7
      months. Small-cell lung cancer patients median survival at limited and extended
      stages of the disease were 9.5 (95% CI 2.9-18.4) compared to 9.2 (95% CI 6.2
      13.7) months. Non-small cell lung cancer patients most frequently were treated by
      surgery (27.0%), surgery and chemotherapy or radiotherapy (19.6%). Small cell
      lung cancer patient treatment included chemo and radiotherapy (27.0%),
      chemotherapy (19.0%), radiotherapy (17.5%), surgery (27.9%). CONCLUSIONS: The
      single center study of female lung cancer diagnosed during 1996-2005 in Lithuania
      show a significantly better chance of survival in resectable non-small cell lung
      cancer. Advanced stages of the disease at the time of diagnosis and choice of
      treatment options of female lung cancer in the country still remains an issue.

PMID- 21097447
TI  - End-of-life care in rheumatolog: room for improvement.

PMID- 21097448
TI  - First observation of the efficacy of IL-1ra to treat tophaceous gout of the
      lumbar spine.

PMID- 21097449
TI  - Pregnancy and reproduction in autoimmune rheumatic diseases.
AB  - Despite evidence for the important role of oestrogens in the aetiology and
      pathophysiology of chronic immune/inflammatory diseases, the previous view of an
      unequivocal beneficial effect of oestrogens on RA compared with a detrimental
      effect on SLE has to be reconsidered. Likewise, the long-held belief that RA
      remits in the majority of pregnant patients has been challenged, and shows that
      only half of the patients experience significant improvement when objective
      disease activity measurements are applied. Pregnancies in patients with SLE are
      mostly successful when well planned and monitored interdisciplinarily, whereas a
      small proportion of women with APS still have adverse pregnancy outcomes in spite
      of the standard treatment. New prospective studies indicate better outcomes for
      pregnancies in women with rare diseases such as SSc and vasculitis. Fertility
      problems are not uncommon in patients with rheumatic disease and need to be
      considered in both genders. Necessary therapy, shortly before or during the
      pregnancy, demands taking into account the health of both mother and fetus. Long
      term effects of drugs on offspring exposed in utero or during lactation is a new
      area under study as well as late effects of maternal rheumatic disease on
      children.

PMID- 21097450
TI  - Pneumocystis jirovecii colonization in patients with systemic autoimmune
      diseases: prevalence, risk factors of colonization and outcome.
AB  - OBJECTIVES: To determine the rate and identify risk factors of Pneumocystis
      jirovecii (P. jirovecii) colonization among patients with systemic autoimmune
      diseases. METHODS: We conducted an observational study in patients with systemic
      autoimmune diseases in an internal medicine department. Each week, five patients
      with systemic diseases were randomly selected for colonization screening.
      Patients complaining of recent respiratory symptoms were excluded. P. jirovecii
      PCR was performed on induced sputum samples. Univariate and multivariate logistic
      regression analyses of clinical and biological data were performed to determine
      predictors of Pneumocystis colonization. Pneumocystis pneumonia occurrence in P.
      jirovecii-positive PCR patients was recorded during a 1-year follow-up. RESULTS:
      P. jirovecii was detected in 11/67 (16%) subjects. Comparing the features in P.
      jirovecii-positive and P. jirovecii-negative PCR patients, only male gender was
      significantly associated with Pneumocystis colonization. In multivariate analysis
      with regard to gender, the higher prevalence of P. jirovecii colonization in men
      was largely explained by higher daily CSs [odds ratio (OR) = 1.6; 95% CI 1.1,
      2.3] and lower total lymphocyte level (OR = 0.9; 95% CI 0.8, 0.99). No P.
      jirovecii-positive PCR patient developed Pneumocystis pneumonia during the 1-year
      follow-up, but corticosteroid amounts were significantly lower at the end of
      follow-up than on inclusion. CONCLUSION: This is the first study on P. jirovecii
      colonization in patients with systemic autoimmune diseases. We found a high
      prevalence of colonization and identified CS therapy and lymphocyte counts as
      risk factors for colonization. We recommend screening for P. jirovecii
      colonization in patients with systemic autoimmune diseases receiving
      immunosuppressant treatment. Further studies are needed to determine the role of
      subclinical colonization in disease transmission and the persistence of
      Pneumocystis colonization.

PMID- 21097451
TI  - Expression of Toll-like receptors 2 and 4 is increased in peripheral blood and
      synovial fluid monocytes of patients with enthesitis-related arthritis subtype of
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: Bacterial trigger possibly causes disease exacerbation in enthesitis
      related arthritis (ERA) patients. Microbes initiate immune responses through Toll
      like receptors (TLRs). We studied TLR expression on blood and SF monocytes and
      the effect of TLR ligands on peripheral blood (PB) mononuclear cells (PBMCs) in
      ERA patients. METHODS: PB from 26 ERA patients and 19 healthy subjects and paired
      SF from 13 patients were collected. Dual-colour flow cytometry was done for TLR
      and CD14 expression. Results are expressed as median fluorescence intensity
      (MFI). Real-time PCR was done for TLRs. PBMCs were stimulated with
      lipopolysaccharide (LPS) or peptidoglycan and levels of IL-6 and MMP-3 measured
      in the culture supernatants. RESULTS: PBMCs from ERA patients had higher
      expression of TLR-2 [MFI 295.5 (48.1-598) vs 179 (68.7-442); P < 0.05] and TLR-4
      [MFI 448 (178-2581) vs 402 (229-569); P < 0.05] as compared with controls. TLR-9
      expression showed no significant difference between the two groups. In paired
      samples, SF mononuclear cells (SFMCs) had higher expression of both TLR-2 [MFI
      485 (141-1683) vs 353 (118-598); P < 0.05] and TLR-4 [MFI 1016 (42.4-3159) vs 513
      (193-2581); P < 0.05] as compared with PBMCs. Difference in TLR-9 expression was
      not significant. TLR RNA expression data were similar. Patients' PBMCs produced
      more IL-6 (13.51 vs 6.54 ng/ml) and MMP-3 (61 vs 32.9 ng/ml) as compared with
      those of the controls, on stimulation by LPS. With peptidoglycan also, IL-6
      (30.58 vs 10.84) and MMP-3 (102.54 vs 49.45) were higher than in controls.
      CONCLUSION: Increased TLR-2 and TLR-4 expression on PBMCs and SFMCs may recognize
      microbial/endogenous ligands and up-regulate IL-6 and MMP-3 leading to disease
      exacerbation.

PMID- 21097452
TI  - What is the best treatment of postpneumonectomy empyema?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether an open surgical approach is
      superior to minimally invasive surgery in patients with postpneumonectomy empyema
      (PPE). Overall 171 papers were found using the reported search, of which 12
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results are tabulated. We conclude that open surgical
      approaches are superior to minimally invasive surgery in terms of empyema
      recurrence rate, mortality and reintervention rate. Minimally invasive surgery
      includes chest tube drainage with or without chemical irrigation and video
      assisted thoracoscopic surgery debridement. Whereas open surgery includes open
      debridement, open window thoracostomy (OWT) and thoracomyoplasty. To allow for an
      accurate comparison, success of an intervention was defined as prevention of
      empyema recurrence. Two studies reported surgical outcomes of patients treated
      with minimally invasive treatment options. They found high mortality rates
      (17.1%) and low success rates (31%) in patients treated by chest tube drainage
      with chemical irrigation. Five studies treated PPE using a combination of
      minimally invasive and open surgical approaches and reported a high
      reintervention rate of 3.5 (range 3-5) and an empyema recurrence rate of 13.3%.
      Higher success rates (6.7 vs. 95%), lower mortality rates (33 vs. 0%) and shorter
      hospital stay (47.5 vs. 17.6 days) were all noted with thoracomyoplasty compared
      to chest tube drainage therapy. Five studies managed PPE using OWT or
      thoracomyoplasty. The time between empyema diagnosis to resolution (3 vs. 38
      months) was much shorter with immediate OWT than with delayed OWT therapy. The
      Clagett procedure resulted in a mean hospital stay of 12.9 days, an operative
      mortality rate of 7.1% and an overall success rate of 81%. Thoracomyoplasty led
      to a mean hospital stay of 34 days with a mortality rate of 6%. The shorter
      hospital stay, lower empyema recurrence rates and lower mortality rates may make
      open surgical approaches a more effective treatment option to minimally invasive
      options.

PMID- 21097453
TI  - Life-threatening hemoptysis due to left inferior phrenic artery to pulmonary
      artery fistula rescued by extracorporeal membrane oxygenation therapy.
AB  - Life-threatening hemoptysis due to bronchiectasis is an emergency and needs
      immediate bronchial angiographic embolization or surgical intervention. Most of
      the bleeding events arise from the bronchial artery. We report a very rare case
      of a patient who had bronchiectasis, but with bleeding from the left phrenic
      artery to pulmonary artery fistula, an artery originating from abdominal aorta.
      In this case, we also demonstrate that extracorporeal membrane oxygenation
      without heparinization as a bridge tool for life-threatening hemoptysis could
      allow the patient to undergo definite therapy more successfully.

PMID- 21097454
TI  - Preoperative evaluation of retroperitoneal venous system anomalies during
      abdominal aortic aneurysm rupture.
AB  - The association of a retroaortic left renal vein and an abdominal aortic aneurysm
      (AAA) fistula is an infrequent event. We present two cases of AAA rupture into
      the retroaortic left renal vein. Preoperative computed tomography (CT) assessment
      showed retroperitoneal bleeding due to a large AAA rupture with an associated
      unusual retroaortic left renal vein. Patients underwent successful arteriovenous
      fistula sutures with abdominal aortoiliac replacement. The patients had
      uneventful recoveries, and they were discharged on the seventh to ninth
      postoperative day (POD) without renal complications. The clinical onset was
      characterized by the unique syndrome: continuous abdominal bruit, abdominal and
      left flank pain with an associated pulsatile mass (Mansour Triad). Moreover
      patients presented with haematuria, proteinuria and a large non-functional left
      kidney on the imaging scan. The CT-scan may suggest the presence of the venous
      anomaly. Unusual anatomical presentation recommends a careful surgical approach
      during AAA operations.

PMID- 21097455
TI  - Current smoking predicts increased operative mortality and morbidity after
      cardiac surgery in the elderly.
AB  - OBJECTIVES: The effect of preoperative smoking status on the outcome of cardiac
      surgery remains unclear. Preoperative cessation may be associated with reduced
      postoperative pulmonary complications and in older patients preoperative smoking
      status appears to have a greater impact on outcome. This study was designed to
      assess the relationship between age, preoperative smoking status and outcomes
      from cardiac surgery. METHODS: We performed a single-centre, retrospective cohort
      study to compare in-patient cardiac surgical mortality and morbidity in current
      smokers and never-smokers. We analysed the cardiac surgical population in its
      entirety and in age-stratified subsets using univariate and logistic regression
      analyses. RESULTS: During a five-year period ending March 2007, 10.8% of all
      patients (n=554) undergoing cardiac surgery were current smokers. Five hundred
      and fifty-four never-smokers undergoing cardiac surgery during the same period
      were identified. Overall, the smokers had a tendency towards higher in-patient
      mortality (4.3 vs. 2.3%, P=0.067) and increased rates of morbidity. Amongst over
      70-year-olds, the current smokers had significantly higher rates of pulmonary
      complications (24.7 vs. 8.2%, P<0.0002), new renal replacement therapy (17.3 vs.
      3.1%, P<0.0001) and infections (44.4 vs. 23.8%, P<0.0007). They had longer
      intensive care stay (6.2 vs. 2.8 days, P=0.002) with more intensive care unit
      readmissions (19.8 vs. 5.2%, P<0.0002) and significantly increased in-patient
      mortality (14.8 vs. 2.1%, P<0.0001). In the elderly smokers, mortality was
      significantly associated with the rate of pulmonary complications (P=0.03).
      Preoperative smoking status remained a predictor of pulmonary complications after
      logistic regression. CONCLUSIONS: The current data strengthen the observation
      that preoperative smoking status is predictive of adverse outcomes of cardiac
      surgery in the elderly. Further study into the effect of preoperative smoking
      cessation in the elderly may inform cessation counselling and the timing of
      surgery.

PMID- 21097456
TI  - Risks and pitfalls in chest tube placement--are we doing it safely?

PMID- 21097457
TI  - Re: An electron microscopic study of left ventricular regression in children with
      transposition of great arteries.

PMID- 21097458
TI  - Risks of combination technique.

PMID- 21097459
TI  - Benign primary cardiac tumours and Cowden's syndrome.

PMID- 21097460
TI  - Metastatic renal cell carcinoma to heart: cardiac surgery versus cardiotoxicity
      of kinase inhibitors.

PMID- 21097461
TI  - Germ cell tumors of the mediastinum.

PMID- 21097462
TI  - Left-sided partial anomalous pulmonary venous connection--should diagnosis lead
      to surgery?

PMID- 21097463
TI  - Re: Temporary epicardial pacing wire removal: not an innocuous procedure.

PMID- 21097464
TI  - Post-pericardiotomy syndrome following lung cancer surgery.

PMID- 21097465
TI  - Towards BioDBcore: a community-defined information specification for biological
      databases.
AB  - The present article proposes the adoption of a community-defined, uniform,
      generic description of the core attributes of biological databases, BioDBCore.
      The goals of these attributes are to provide a general overview of the database
      landscape, to encourage consistency and interoperability between resources and to
      promote the use of semantic and syntactic standards. BioDBCore will make it
      easier for users to evaluate the scope and relevance of available resources. This
      new resource will increase the collective impact of the information present in
      biological databases.

PMID- 21097468
TI  - PCRPi-DB: a database of computationally annotated hot spots in protein
      interfaces.
AB  - Protein-protein interactions are central to almost any cellular process. Although
      typically protein interfaces are large, it is well established that only a
      relatively small region, the so-called 'hot spot', contributes the most to the
      total binding energy. There is a clear interest in identifying hot spots because
      of its application in drug discovery and protein design. Presaging Critical
      Residues in Protein Interfaces Database (PCRPi-DB) is a public repository that
      archives computationally annotated hot spots in protein complexes for which the
      3D structure is known. Hot spots have been annotated using a new and highly
      accurate computational method developed in the lab. PCRPi-DB is freely available
      to the scientific community at http://www.bioinsilico.org/PCRPIDB. Besides
      browsing and querying the contents of the database, extensive documentation and
      links to relevant on-line resources and contents are available to users. PCRPi-DB
      is updated on a weekly basis.

PMID- 21097467
TI  - Pseudouridine at position 55 in tRNA controls the contents of other modified
      nucleotides for low-temperature adaptation in the extreme-thermophilic
      eubacterium Thermus thermophilus.
AB  - Pseudouridine at position 55 (Psi55) in eubacterial tRNA is produced by TruB. To
      clarify the role of the Psi55 modification, we constructed a truB gene disruptant
      (DeltatruB) strain of Thermus thermophilus which is an extreme-thermophilic
      eubacterium. Unexpectedly, the DeltatruB strain exhibited severe growth
      retardation at 50  degrees C. We assumed that these phenomena might be caused by
      lack of RNA chaperone activity of TruB, which was previously hypothetically
      proposed by others. To confirm this idea, we replaced the truB gene in the genome
      with mutant genes, which express TruB proteins with very weak or no enzymatic
      activity. However the growth retardation at 50  degrees C was not rescued by
      these mutant proteins. Nucleoside analysis revealed that Gm18, m(5)s(2)U54 and
      m(1)A58 in tRNA from the DeltatruB strain were abnormally increased. An in vitro
      assay using purified tRNA modification enzymes demonstrated that the Psi55
      modification has a negative effect on Gm18 formation by TrmH. These experimental
      results show that the Psi55 modification is required for low-temperature
      adaptation to control other modified. (35)S-Met incorporation analysis showed
      that the protein synthesis activity of the DeltatruB strain was inferior to that
      of the wild-type strain and that the cold-shock proteins were absence in the
      DeltatruB cells at 50 degrees C.

PMID- 21097466
TI  - RTEL1: an essential helicase for telomere maintenance and the regulation of
      homologous recombination.
AB  - Telomere maintenance and DNA repair are crucial processes that protect the genome
      against instability. RTEL1, an essential iron-sulfur cluster-containing helicase,
      is a dominant factor that controls telomere length in mice and is required for
      telomere integrity. In addition, RTEL1 promotes synthesis-dependent strand
      annealing to direct DNA double-strand breaks into non-crossover outcomes during
      mitotic repair and in meiosis. Here, we review the role of RTEL1 in telomere
      maintenance and homologous recombination and discuss models linking RTEL1's
      enzymatic activity to its function in telomere maintenance and DNA repair.

PMID- 21097469
TI  - Single-Molecule characterization of oligomerization kinetics and equilibria of
      the tumor suppressor p53.
AB  - The state of oligomerization of the tumor suppressor p53 is an important factor
      in its various biological functions. It has a well-defined tetramerization
      domain, and the protein exists as monomers, dimers and tetramers in equilibrium.
      The dissociation constants between oligomeric forms are so low that they are at
      the limits of measurement by conventional methods in vitro. Here, we have used
      the high sensitivity of single-molecule methods to measure the equilibria and
      kinetics of oligomerization of full-length p53 and its isolated tetramerization
      domain, p53tet, at physiological temperature, pH and ionic strength using
      fluorescence correlation spectroscopy (FCS) in vitro. The dissociation constant
      at 37  degrees C for tetramers dissociating into dimers for full-length p53 was
      50 +/- 7 nM, and the corresponding value for dimers into monomers was 0.55 +/-
      0.08 nM. The half-lives for the two processes were 20 and 50 min, respectively.
      The equivalent quantities for p53tet were 150 +/- 10 nM, 1.0 +/- 0.14 nM, 2.5 +/-
      0.4 min and 13 +/- 2 min. The data suggest that unligated p53 in unstressed cells
      should be predominantly dimeric. Single-molecule FCS is a useful procedure for
      measuring dissociation equilibria, kinetics and aggregation at extreme
      sensitivity.

PMID- 21097470
TI  - PlantTFDB 2.0: update and improvement of the comprehensive plant transcription
      factor database.
AB  - We updated the plant transcription factor (TF) database to version 2.0 (PlantTFDB
      2.0, http://planttfdb.cbi.pku.edu.cn) which contains 53,319 putative TFs
      predicted from 49 species. We made detailed annotation including general
      information, domain feature, gene ontology, expression pattern and ortholog
      groups, as well as cross references to various databases and literature citations
      for these TFs classified into 58 newly defined families with computational
      approach and manual inspection. Multiple sequence alignments and phylogenetic
      trees for each family can be shown as Weblogo pictures or downloaded as text
      files. We have redesigned the user interface in the new version. Users can search
      TFs with much more flexibility through the improved advanced search page, and the
      search results can be exported into various formats for further analysis. In
      addition, we now provide web service for advanced users to access PlantTFDB 2.0
      more efficiently.

PMID- 21097471
TI  - LSD: a leaf senescence database.
AB  - By broad literature survey, we have developed a leaf senescence database (LSD,
      http://www.eplantsenescence.org/) that contains a total of 1145 senescence
      associated genes (SAGs) from 21 species. These SAGs were retrieved based on
      genetic, genomic, proteomic, physiological or other experimental evidence, and
      were classified into different categories according to their functions in leaf
      senescence or morphological phenotypes when mutated. We made extensive
      annotations for these SAGs by both manual and computational approaches, and users
      can either browse or search the database to obtain information including
      literatures, mutants, phenotypes, expression profiles, miRNA interactions,
      orthologs in other plants and cross links to other databases. We have also
      integrated a bioinformatics analysis platform WebLab into LSD, which allows users
      to perform extensive sequence analysis of their interested SAGs. The SAG
      sequences in LSD can also be downloaded readily for bulk analysis. We believe
      that the LSD contains the largest number of SAGs to date and represents the most
      comprehensive and informative plant senescence-related database, which would
      facilitate the systems biology research and comparative studies on plant aging.

PMID- 21097472
TI  - Central venous pressure and impaired renal function in patients with acute heart
      failure.
AB  - AIMS: To determine the relationship between central venous pressure (CVP) and
      renal function in patients with acute heart failure (AHF) presenting to the
      emergency department. METHODS AND RESULTS: Central venous pressure was determined
      non-invasively using compression sonography in 140 patients with AHF at
      presentation. Worsening renal function (WRF) was defined as an increase in serum
      creatinine >= 0.3 mg/dL during hospitalization. In the study cohort [age 77 +/-
      12 years, B-type natriuretic peptide 1862 +/- 1564 pg/mL, left ventricular
      ejection fraction 40 +/- 15%, estimated glomerular filtration rate (eGFR) 58 +/-
      28 mL/min, and CVP 13.2 +/- 6.9 cmH(2)O], 51 patients (36%) developed WRF. No
      significant association between CVP at presentation or discharge and concomitant
      eGFR (r = 0.005, P = 0.419 and r = 0.013, P = 0.313, respectively) was observed.
      However, in patients with systolic blood pressure (SBP) <110 mmHg and concomitant
      high CVP (>15 cmH(2)O), eGFR was significantly lower at presentation and
      discharge (29 +/- 17 vs. 47 +/- 19 mL/min/1.73 m(2), P = 0.039 and 26 +/- 10 vs.
      53 +/- 26 mL/min/1.73 m(2), P = 0.013, respectively). Central venous pressure at
      presentation and at discharge did not differ between patients with or without in
      hospital WRF (12.6 +/- 7.2 vs. 13.5 +/- 6.7 cmH(2)O, P = 0.503 and 7.4 +/- 6.5
      vs. 7.7 +/- 5.7 cmH(2)O, P = 0.799, respectively) (receiver-operating
      characteristic analysis 0.543, P = 0.401 and 0.531, P = 0.625, respectively).
      However, patients with CVP in the lowest tertile (<10 cmH(2)O) at presentation
      were more likely to develop WRF within the first 24 h than patients with CVP in
      the highest tertile (>15 cmH(2)O) (18 vs. 4%, P = 0.046). CONCLUSION: In AHF,
      combined low SBP and high CVP predispose to lower eGFR. However, lower CVP may
      also be associated with short-term WRF. The pathophysiology of WRF and the role
      of CVP seem to be more complex than previously thought.

PMID- 21097473
TI  - The risk of success: cultural determinants of chronic disease and sexually
      transmitted infections among urban Chinese men.
AB  - During the 1950s and 1960s, the People's Republic of China successfully waged a
      series of public health campaigns to control the infectious diseases that were
      ravaging them as a nation. This included a campaign that targeted the social
      roots of sexually transmitted infections (STIs). China is now facing a new
      disease profile that includes emerging epidemics of chronic disease as well as
      reemerging epidemics of STIs. Many of these diseases are strongly associated with
      gender and occupation, suggesting need for a critical model of health literacy
      that recognizes the role of social risk in promoting risky behaviors rather than
      focusing on a simple model that disseminates knowledge about biomedical risk.
      Such a model is useful for explaining why people armed with knowledge about
      biomedical risk continue to engage in risky behaviors. This article focuses on
      the social risks that wealthy Chinese businessmen and government officials
      negotiate on a daily basis. It highlights the concept of guanxi that is so
      central to building relationships in China and explains the traditional process
      of yingchou used to establish and maintain relationships among this cadre of men
      who depend on one another for political and economic success. This process, which
      has become pervasive in China's era of market reform, requires men to engage in
      frequent practices of smoking, drinking, eating and female-centered entertainment
      that are contributing both to their success and to their increasing vulnerability
      to chronic disease and STIs. The paper concludes by offering some alternative
      approaches to addressing this emerging disease pattern among this particular
      segment of China's population.

PMID- 21097474
TI  - The R-R-type MYB-like transcription factor, AtMYBL, is involved in promoting leaf
      senescence and modulates an abiotic stress response in Arabidopsis.
AB  - Functional analysis of a putative novel transcription factor Arabidopsis MYB-like
      protein designated AtMYBL, which contains two predicted DNA-binding domains, was
      performed. The physiological role of the R-R-type MYB-like transcription factor
      has not been reported in any plant. Analyses of an AtMYBL promoter-beta
      glucuronidase (GUS) construct revealed substantial gene expression in old leaves
      and induction of GUS activity by ABA and salt stress. AtMYBL-overexpressing
      plants displayed a markedly enhanced leaf senescence phenotype. Moreover, the
      ectopic expression of the AtMYBL gene was very significantly influential in
      senescence parameters including Chl content, membrane ion leakage and the
      expression of senescence-related genes. Although the seed germination rate was
      improved under ABA and saline stress conditions in the AtMYBL-overexpressing
      plants, decreased salt tolerance was evident compared with the wild type and
      atmybl RNA interference lines during later seedling growth when exposed to long
      term salt stress, indicating that AtMYBL protein is able to developmentally
      regulate stress sensitivity. Furthermore, AtMYBL protein activated the
      transcription of a reporter gene in yeast. Green fluorescent protein-tagged
      AtMYBL was localized in the nuclei of transgenic Arabidopsis cells. Taken
      together, these results suggest that AtMYBL functions in the leaf senescence
      process, with the abiotic stress response implicated as a putative potential
      transcription factor.

PMID- 21097475
TI  - Regulated AtHKT1 gene expression by a distal enhancer element and DNA methylation
      in the promoter plays an important role in salt tolerance.
AB  - Through sos3 (salt overly sensitive 3) suppressor screening, two allelic
      suppressor mutants that are weak alleles of the strong sos3 suppressor sos3hkt1-1
      were recovered. Molecular characterization identified T-DNA insertions in the
      distal promoter region of the Arabidopsis thaliana HKT1 (AtHKT1, At4g10310) in
      these two weak sos3 suppressors, which results in physical separation of a tandem
      repeat from the proximal region of the AtHKT1 promoter. The tandem repeat is
      approximately 3.9 kb upstream of the ATG start codon and functions as an enhancer
      element to promote reporter gene expression. A putative small RNA target region
      about 2.6 kb upstream of the ATG start codon is heavily methylated. CHG and CHH
      methylation but not CG methylation is significantly reduced in the small RNA
      biogenesis mutant rdr2, indicating that non-CG methylation in this region is
      mediated by small RNAs. Analysis of AtHKT1 expression in rdr2 suggests that non
      CG methylation in the putative small RNA target region represses AtHKT1
      expression in shoots. The DNA methylation-deficient mutant met1-3 has nearly
      complete loss of total cytosine methylation in the putative small RNA target
      region and is hypersensitive to salt stress. The putative small RNA target region
      and the tandem repeat are essential for maintaining AtHKT1 expression patterns
      crucial for salt tolerance.

PMID- 21097476
TI  - 12-oxo-phytodienoic acid-glutathione conjugate is transported into the vacuole in
      Arabidopsis.
AB  - While exogenous toxic compounds such as herbicides are thought to be sequestered
      into vacuoles in the form of glutathione (GSH) conjugates, little is understood
      about natural plant products conjugated with GSH. To identify natural products
      conjugated with GSH in plants, metabolites in the Arabidopsis gamma-glutamyl
      transpeptidase (ggt) 4 knockout mutants that are blocked in the degradation of
      GSH conjugates in the vacuole were compared with those in wild-type plants. Among
      the metabolites identified, one was confirmed to be the 12-oxo-phytodienoic acid
      (OPDA)-GSH conjugate, indicating that OPDA, a precursor of jasmonic acid (JA), is
      transported into the vacuole as a GSH conjugate.

PMID- 21097479
TI  - Characterization of non-pulmonary vein foci with an EnSite array in patients with
      paroxysmal atrial fibrillation.
AB  - AIMS: Non-pulmonary vein (PV) foci are sometimes difficult to identify and
      eliminate. The EnSite array (EA) reveals the detailed beat-to-beat virtual
      activation. This study aimed to characterize non-PV foci using the EA. METHODS
      AND RESULTS: Sixty-five patients with paroxysmal atrial fibrillation (AF) were
      included. All had ectopy initiating AF and/or focal atrial tachycardia analysed
      using the EA. All patients underwent PV isolation (PVI) and additional ablation
      of non-PV foci if present. The EA revealed 59 PV foci in 48 patients (Group P)
      and 19 non-PV foci in 17 patients (Group N). In Group N, 12 patients (71%) also
      had 17 PV foci. The non-PV foci were frequently distributed in the left atrial
      (LA) roof (n = 5) and superior vena cava (n = 5). Pulmonary vein isolation during
      on-going AF terminated AF in 34 of 37 in Group P (92%) and 4 of 14 in Group N
      (29%) patients (P < 0.0001). All non-PV foci were eliminated by an EA-guided
      ablation. During a 23 +/- 10 month follow-up, 11 patients (17%) had AF
      recurrences, mainly due to LA-PV reconnection. CONCLUSION: Non-PV foci are
      prevalent in the LA roof and SVC sites, but can originate from other sites as
      well. When non-PV foci are observed, PVI may be insufficient and should be
      supplemented with non-PV foci ablation.

PMID- 21097478
TI  - Use of an implantable loop recorder to increase the diagnostic yield in
      unexplained syncope: results from the PICTURE registry.
AB  - AIMS: To collect information on the use of the Reveal implantable loop recorder
      (ILR) in the patient care pathway and to investigate its effectiveness in the
      diagnosis of unexplained recurrent syncope in everyday clinical practice. METHODS
      AND RESULTS: Prospective, multicentre, observational study conducted in 2006-2009
      in 10 European countries and Israel. Eligible patients had recurrent unexplained
      syncope or pre-syncope. Subjects received a Reveal Plus, DX or XT. Follow up was
      until the first recurrence of a syncopal event leading to a diagnosis or for >=1
      year. In the course of the study, patients were evaluated by an average of three
      different specialists for management of their syncope and underwent a median of
      13 tests (range 9-20). Significant physical trauma had been experienced in
      association with a syncopal episode by 36% of patients. Average follow-up time
      after ILR implant was 10+/-6 months. Follow-up visit data were available for 570
      subjects. The percentages of patients with recurrence of syncope were 19, 26, and
      36% after 3, 6, and 12 months, respectively. Of 218 events within the study, ILR
      guided diagnosis was obtained in 170 cases (78%), of which 128 (75%) were
      cardiac. CONCLUSION: A large number of diagnostic tests were undertaken in
      patients with unexplained syncope without providing conclusive data. In contrast,
      the ILR revealed or contributed to establishing the mechanism of syncope in the
      vast majority of patients. The findings support the recommendation in current
      guidelines that an ILR should be implanted early rather than late in the
      evaluation of unexplained syncope.

PMID- 21097480
TI  - Relationship between cardiac autonomic function and sustained ventricular
      tachyarrhythmias in patients with an implantable cardioverter defibrillators.
AB  - AIMS: Low left ventricular ejection fraction (LVEF) is the main indication of
      implantable cardioverter defibrillators (ICD) in patients with dilated
      cardiomyopathy (DCM) for the primary prevention of sudden cardiac death, but ICD
      therapy at follow-up occurs in a minority of patients. We investigated whether
      heart rate variability (HRV) may improve risk stratification in DCM patients.
      METHODS AND RESULTS: We studied 42 patients (age 67.3 +/- 3.5; 37 males) who had
      undergone ICD implant for either idiopathic or ischaemic DCM (LVEF <40%) 34.6 +/-
      19.7 months prior to the study (range 6-84). Patients underwent 24 h
      electrocardiographic Holter monitoring, and HRV was assessed over 2 hours in the
      afternoon showing stable sinus rhythm. Left ventricular ejection fraction was
      measured by two-dimensional echocardiography. The serum levels of C-reactive
      protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also
      obtained. The primary endpoint was the occurrence of appropriate ICD shocks in
      the 6 months preceding the study. The occurrence of appropriate ICD discharge
      from ICD implant was considered as a secondary endpoint. In the last 6 months,
      appropriate ICD shocks had occurred in seven patients (17%). There were no
      differences between patients with and without ICD shocks in clinical variables,
      as well as in LVEF and in C-reactive protein and NT-proBNP serum levels. In
      contrast, most HRV parameters were significantly depressed in patients with,
      compared with those without, ICD shocks; the most significant difference was
      shown for the average of the standard deviations of RR intervals in all
      consecutive 5 min segments (n 1/4 12) within the 2 h (26.7 +/- 9 vs. 39.7 +/- 14
      ms; P = 0.02) in the time domain and for LF amplitude (8.4 +/- 3 vs. 14.8 +/- 7
      ms; P = 0.02) in the frequency domain. Implantable cardioverter defibrillator
      discharge had occurred in 11 patients (26%) since ICD implant (average 35
      months). No clinical or laboratory variable showed significant differences
      between patients with or without ICD discharge, except very low-frequency (VLF)
      amplitude (23.8 +/- 7 vs. 30.8 +/- 10.6 ms, respectively; P = 0.049). CONCLUSION:
      In ICD patients with reduced LVEF, several depressed HRV indices were
      significantly associated with appropriate ICD shocks in the previous 6 months,
      and VLF amplitude was the only variable significantly associated with ICD shocks
      recorded since ICD implant. These data suggest that full HRV analysis might be
      helpful for improving risk stratification for life-threatening ventricular
      arrhythmias and ICD indication in patients with DCM.

PMID- 21097481
TI  - Reducing operator radiation exposure during cardiac resynchronization therapy.
AB  - AIMS: To quantify the reduction in equivalent dose at operator's hand that can be
      achieved by placement of a radiation-absorbing drape (RADPAD) during long-lasting
      cardiac resynchronization therapy (CRT) procedures. METHODS AND RESULTS: This is
      a prospective observational study that included 22 consecutive patients with drug
      refractory heart failure who underwent implantation of a CRT device. The cases
      were randomly assigned to Group A (11 cases), performed without RADPAD, and to
      Group B (11 cases), performed using RADPAD. Dose equivalent at the examiner's
      hand was measured as H(p)(0.07) and as a time-adjusted H(p)(0.07) rate (mGy/min)
      with a direct reading dosimeter. The mean fluoroscopy time was 20.8 +/- 7.7 min
      and the mean dose area product (DAP) was 118.6 +/- 45.3 Gy cm(2). No significant
      differences were found between body mass index, fluoroscopy time, and DAP between
      patients examined with or without RADPAD. The correlation between the fluoroscopy
      time and the DAP was high (R(2) = 0.94, P < 0.001). Mean dose and dose rate
      measurement without the RADPAD at the finger and hand were H(p)(0.07) = 1.27 +/-
      0.47 mGy per procedure and H(p)(0.07) rate = 0.057 +/- 0.011 mGy/min,
      respectively. The dosage was reduced with the RADPAD to H(p)(0.07) = 0.48 +/-
      0.20 (P < 0.05) and to H(p)(0.07) rate = 0.026 +/- 0.008 (P < 0.001),
      respectively. CONCLUSION: A mean reduction of 54% in the equivalent dose rate to
      the operator's hand can be achieved with the use of RADPAD. The use of the RADPAD
      in CRT devices implantation will make unlikely the necessity of limiting the
      yearly number of implants for high volume operators.

PMID- 21097482
TI  - Remote monitoring for active cardiovascular implantable electronic devices: a
      European survey.
AB  - This survey sampled today's European practices in the use of remote monitoring
      (RM) for the follow-up of active cardiovascular implantable electronic devices.
      Eighty-five per cent of the responding centres are currently using RM. For the
      majority, RM is expected to increase importantly within 5 years, and it has
      already led to a new organization of care based on dedicated allied professionals
      and/or the creation of RM units. There are still major limitations for the
      development of RM, such as ethical and legal aspects, reimbursement issues, and
      the lack of specific national- and European-updated guidelines which need to be
      informed.

PMID- 21097483
TI  - Comprehensive dose survey of breast screening in Ireland.
AB  - The primary purpose of this study was to evaluate the impact of digital
      mammography screening on breast dose by analysing the results of a patient dose
      survey of the Irish breast screening programme. Results from the survey were used
      to determine a dose reference level for the screening programme. Approximately,
      100 examinations were acquired for each of the digital mammography systems
      operational in the screening programme. Each examination consisted of two
      standard views of each breast. The mean glandular dose for each acquired image
      was calculated. The dose reference level was established by calculating the 95th
      percentile of the average mean glandular dose for the average compressed breast
      thickness of the mediolateral oblique views. The overall average mean glandular
      dose per examination was 2.72 +/- 0.04 mGy. The average compressed breast
      thickness was 61.4 +/- 0.03 mm. The average compression force was 109 +/- 7 N. A
      dose reference level value of 1.75 mGy was established for the screening
      programme. The results of this clinical dose survey provide a valuable indication
      of the dose performance of modern full field digital mammographic imaging
      systems. The results demonstrate clearly the dose benefits of digital
      mammography. The dose benefit of digital screening was further demonstrated by
      the establishment of a comparatively lower diagnostic reference level for the
      screening programme. The comparison of the dose performance of individual X-ray
      systems with the diagnostic reference level highlights the need for more
      optimisation within the service.

PMID- 21097484
TI  - Methodology of a study on the French population exposure to 50 Hz magnetic
      fields.
AB  - The characterisation of population exposure to a 50-Hz magnetic field (MF) is
      important for assessing health effects of electromagnetic fields. With the aim of
      estimating and characterising the exposure of the French population to 50-Hz MFs,
      two representative samples of the population were made. A random selection method
      based on the distribution of households in different regions of France was used.
      The samples were carried out starting from a random polling of telephone numbers
      of households (listed, unlisted fixed phones and cell phones only). A total of
      95,362 telephone numbers were dialed to have 2148 volunteers (1060 children and
      1088 adults). They all agreed to carrying an EMDEX II meter, measuring and
      recording MFs, and to filling out a timetable for a 24-hour period. In this
      article, the methodology of the sample selection and the collection of all
      necessary information for the realisation of this study are presented.

PMID- 21097485
TI  - Radiation protection for pregnant workers and their offspring: a recommended
      approach for monitoring.
AB  - Radiation protection of pregnant workers and their offspring is an issue that has
      been referenced in the literature by the International Commission on Radiological
      Protection (ICRP), the International Atomic Energy Agency (IAEA) and other
      international institutions. Several documents of the ICRP address the issue of
      the protection of the pregnant workers. The new ICRP recommendations refer to the
      control of working conditions of a pregnant worker, after declaration of
      pregnancy, such that it is unlikely that the additional dose to the fetus will
      exceed about 1 mSv during the remainder of pregnancy. The IAEA Basic Safety
      Standards present similar recommendations. The IAEA is preparing a technical
      document that provides guidance on these issues.

PMID- 21097486
TI  - Emission rates of alpha particles from supports with different surface conditions
      in direct deposition sources.
AB  - Direct deposition is the only method that can be utilised for the standardisation
      of radioactive solutions because there is no deposition loss on a support. The
      present study investigated how much the roughness of the support influences the
      emission rate of alpha particles for direct deposition sources from the practical
      viewpoint of use of the method. A number of samples were prepared by evaporating
      a 0.1-ml aliquot of a dilute nitric acid aqueous solution that contained (241)Am
      on stainless steel supports with four different surface conditions; untreated
      supports were either polished (using metal abrasives available commercially) or
      not polished, and buffed supports (grid size of #400) were either polished or not
      polished. Alpha spectrometry of the samples revealed that the detection
      efficiency was significantly different between the non-polished and polished
      supports; the former was lower by 3 % than the latter for both the untreated and
      buffed supports. Microscopic observations clarified that the counting loss was
      attributed to irregular flaws or polishing lines on the non-polished supports,
      most of which were found to be in the order of submicron in depth and were
      diminished on the polished supports. One may usually assume that a direct
      deposition source offers no counting loss if its entire energy spectrum is seen
      above a low-energy discrimination limit of the spectrometer. However, this should
      be experimentally confirmed using a solution with known activity. It was
      difficult to identify the counting loss for the buffed supports without polishing
      because their energy spectra showed little degradation.

PMID- 21097487
TI  - Comparison between pulse waveform analysis and thermodilution cardiac output
      determination in patients with severe pre-eclampsia.
AB  - BACKGROUND: This study compared cardiac output (CO) measurements derived from
      pulse waveform analysis with values obtained by thermodilution (TD), in patients
      with post-partum complications of severe pre-eclampsia. METHODS: Eighteen
      patients were recruited, 24-96 h post-delivery. After central venous calibration
      of the pulse waveform analysis monitor (LiDCOplus), CO readings were compared
      with those obtained by the TD method and repeated twice at 15 min intervals. The
      comparison was repeated after peripheral venous calibration. Further comparisons
      were made in eight patients at 120 and 240 min after peripheral venous
      calibration. RESULTS: Data were pooled for measurements at 0, 15, and 30 min
      after calibration. For the comparison between TD and LiDCOplus using central
      venous calibration, TD exhibited a significant positive bias of 0.58 litre min-1
      [95% confidence interval (CI): 0.77 to 0.39]. After peripheral venous
      calibration, there was no significant bias [0.16 litre min-1 (95% CI: -0.37 to
      0.06)]. The estimated limits of agreement for central and peripheral venous
      calibrations were -2.12 to 0.96 and -1.50 to 1.20 litre min-1, respectively. When
      comparing LiDCOplus and TD, there was no time-based effect at 120 or 240 min post
      peripheral calibration. CONCLUSIONS: Central and peripheral venous calibrations
      of the LiDCOplus monitor were associated with clinically insignificant bias when
      compared with TD. Limits of agreement were within the recommendation of 30% for
      acceptance of a new CO technique when compared with current reference methods.
      This form of minimally invasive CO monitoring may have a valuable role in
      obstetric critical care.

PMID- 21097488
TI  - Changes in serum concentrations of soluble vascular endothelial growth factor
      receptor-1 after pregnancy.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is the most potent
      stimulator of angiogenesis. It mediates its activity through two membrane-bound
      receptors, VEGFR-1 and VEGFR-2, both expressed in the placenta. Beginning in
      early pregnancy, the soluble form of the first, sVEGFR-1, binds and inhibits most
      of the biological actions of circulating VEGF. After delivery, it disappears from
      the maternal circulation. METHODS: We determined the biological elimination rate
      of endogenous sVEGFR-1 after term pregnancy in serial venous samples obtained
      during and after elective Caesarean sections (n=8), and we demonstrated the
      relationship between serum sVEGFR-1 and VEGF after mid-trimester legal
      termination of pregnancy (n = 5), by analysing their concentrations using
      immunoassays (ELISA). RESULTS: The disappearance of sVEGFR-1 from circulation
      after Caesarean delivery was biphasic with a rapid half-life of 3.4 h (2.2-7.5 h;
      median, range) and a slow one of 29 h (17-94 h). After mid-trimester legal
      termination of pregnancy the sVEGFR-1 concentrations decreased and those of free
      VEGF simultaneously increased with a highly significant negative correlation with
      each other (r = -0.90, P < 0.0001). CONCLUSIONS: The disappearance of endogenous
      sVEGFR-1 after pregnancy is biphasic, and it is associated with a simultaneous
      increase in free VEGF concentrations.

PMID- 21097489
TI  - Parent and teacher ratings of attention during a year-long methylphenidate trial
      in children treated for cancer.
AB  - OBJECTIVE: Longitudinally examine attention performance in childhood cancer
      survivors prescribed methylphenidate (MPH) to ameliorate cognitive late effects,
      comparing measures for inter-rater and inter-method discrepancies. METHODS:
      Survivors of acute lymphoblastic leukemia (n = 33) or brain tumor (n = 35), mean
      age 11.11 +/- 0.37 years, completed a 12-month, open-label trial of MPH. Conners'
      Parent and Teacher Rating Scales were completed at baseline, 1, 3, 6, and 12
      months. The Conners' Continuous Performance Test (CPT) was completed at baseline
      and 12 months. RESULTS: Improved attention was reported after 1 month of MPH (p <
      .05), with relative stability throughout the trial. Inter-rater agreement was low
      to-moderate (ICC = -.06 to .46). Observer ratings correlated with select CPT
      indices at baseline (p < .05), but not at 12 months. CONCLUSIONS: Childhood
      cancer survivors' attention improved after 1 month on MPH. Modest agreement
      between parents and teachers, and low-to-moderate correlations between behavior
      ratings and performance-based attention measures highlight a need for multimodal
      assessment.

PMID- 21097491
TI  - Decreased language lateralization is characteristic of psychosis, not auditory
      hallucinations.
AB  - Decreased language lateralization is a well-replicated finding in psychotic
      patients. It is currently unclear, however, whether this abnormality is related
      to a particular symptom of psychosis or to psychosis in general. It has been
      argued that decreased language lateralization may be related to auditory verbal
      hallucinations. To elucidate this, these hallucinations should be studied in
      isolation. Thirty-five patients with a psychotic disorder, 35 non-psychotic
      subjects with relatively isolated auditory verbal hallucinations and 35 healthy
      control subjects participated in this study. All subjects were scanned on a 3T
      magnetic resonance imaging scanner, while covertly performing a paced verbal
      fluency task. In order to measure performance on the task, one additional task
      block was presented during which subjects had to generate words overtly. In
      addition to calculating language lateralization indices, group-wise brain
      activation during verbal fluency was compared between the three groups. Task
      performance was nearly maximal for all groups and did not differ significantly
      between the groups. Compared with the healthy control subjects and non-psychotic
      subjects with auditory verbal hallucinations, language lateralization was
      significantly reduced for the patient group. In addition, the patients displayed
      significantly greater activity in the right precentral gyrus and left insula when
      compared with the healthy control subjects and the non-psychotic subjects with
      auditory verbal hallucinations. Furthermore, the patients showed greater activity
      in the right superior parietal lobule when compared with the healthy control
      subjects. Lateralization indices did not differ significantly between the non
      psychotic subjects with auditory verbal hallucinations and the healthy control
      subjects. Moreover, there were no significant differences in brain activation
      during verbal fluency between the two non-psychotic groups. As language
      lateralization was not significantly reduced in the non-psychotic individuals
      with auditory verbal hallucinations, a direct relationship between auditory
      verbal hallucinations and decreased language lateralization can not be
      established at present.

PMID- 21097490
TI  - The primary visual cortex, and feedback to it, are not necessary for conscious
      vision.
AB  - A compelling single case report of visual awareness (visual qualia) without
      primary visual cortex would be sufficient to refute the hypothesis that the
      primary visual cortex and the back-projections to it are necessary for conscious
      visual experience. In a previous study, we emphasized the presence of crude
      visual awareness in Patient G.Y., with a lesion of the primary visual cortex, who
      is aware of, and able to discriminate, fast-moving visual stimuli presented to
      his blind field. The visual nature of Patient G.Y.'s blind field experience has
      since been questioned and it has been suggested that the special circumstances of
      repeated testing over decades may have altered Patient G.Y.'s visual pathways. We
      therefore sought new evidence of visual awareness without primary visual cortex
      in patients for whom such considerations do not apply. Three patients with
      hemianopic field defects (Patient G.N. and Patient F.B. with MRI confirmed
      primary visual cortex lesions, Patient C.G. with an inferred lesion) underwent
      detailed psychophysical testing in their blind fields. Visual stimuli were
      presented at different velocities and contrasts in two- and four-direction
      discrimination experiments and the direction of motion and awareness reported
      using a forced-choice paradigm. Detailed verbal reports were also obtained of the
      nature of the blind field experience with comparison of the drawings of the
      stimulus presented in the blind and intact fields, where possible. All three
      patients reported visual awareness in their blind fields. Visual awareness was
      significantly more likely when a moving stimulus was present compared to no
      stimulus catch trials (P < 0.01 for each subject). Psychophysical performance in
      Patient F.B. and Patient G.N. was consistent with the Riddoch syndrome, with
      higher levels of visual awareness for moving compared to static stimuli (P <
      0.001) and intact direction discrimination (P < 0.0001 for two- and four
      direction experiments). Although the blind field experience of all three subjects
      was degraded, it was clearly visual in nature. We conclude that the primary
      visual cortex or back-projections to it are not necessary for visual awareness.

PMID- 21097492
TI  - Humans use internal models to construct and update a sense of verticality.
AB  - Internal models serve sensory processing, sensorimotor integration and motor
      control. They could be a way to construct and update a sense of verticality, by
      combining vestibular and somatosensory graviception. We tested this hypothesis by
      investigating self-orientation relative to gravity in 39 normal subjects and in
      subjects with various somatosensory losses showing either a complete
      deafferentation of trunk and lower limbs (14 paraplegic patients after complete
      traumatic spinal cord injury) or a gradient in the degree of a hemibody sensory
      loss (23 hemiplegic patients after stroke). We asked subjects to estimate, in the
      dark, the direction of the Earth vertical in two postural conditions-upright and
      at lateral whole body tilt. For upright conditions, verticality estimates were
      not different from the direction of the Earth vertical in normal (0.24 degrees 
      +/- 1; P = 0.42) and paraplegic subjects (0.87 degrees  +/- 0.9; P = 0.14). The
      within-subject variability was much greater in hemiplegic than in normal subjects
      (2.05 degrees  +/- 1.15 versus 1.06 degrees  +/- 0.4; P < 0.01) and greater in
      paraplegic than in normal subjects (1.13 degrees  +/- 0.4 versus 0.72 degrees  +/
      0.4; P < 0.01). These findings indicate that, even if vestibular graviception is
      intact, somaesthetic graviception contributes to the sense of verticality,
      leading to a more robust judgement about the direction of verticality when
      vestibular and somaesthetic graviception yield congruent information. As
      expected, when normal subjects were tilted, their verticality estimates were
      biased in the direction of the body tilt (5.55 degrees  +/- 3.9). This normal
      modulation of verticality perception (Aubert effect), was preserved in
      hemiplegics on the side of the normoaesthetic hemibody (ipsilesional) (6.09
      degrees  +/- 6.3), and abolished both in paraplegics (1.06 degrees  +/- 2.5) and
      in hemiplegics (0.04 degrees  +/- 6.7) on the side of hypoaesthetic hemibody
      (contralesional). This incongruence did not exist in deafferented paraplegics who
      exclusively used vestibular graviception with a similar efficacy no matter what
      the lateral body position. The Aubert effect was not an on-off phenomenon since
      the degree of hemiplegics' somatosensory loss correlated with the modulation of
      verticality perception when they were tilted to the side of hypoaesthetic
      hemibody (r = -0.55; P < 0.01). The analysis of anatomical correlates showed that
      the Aubert effect required the integrity of the posterolateral thalamus. This
      study reveals the existence of a synthesis of vestibular and somaesthetic
      graviception for which the posterolateral thalamus plays a major role. This
      corresponds to a primary property of internal models and yields the neural bases
      of the Aubert effect. We conclude that humans construct and update internal
      models of verticality in which somatosensory information plays an important role.

PMID- 21097493
TI  - Key role of striatal cholinergic interneurons in processes leading to arrest of
      motor stereotypies.
AB  - Motor stereotypy is a key symptom of various disorders such as Tourette's
      syndrome and punding. Administration of nicotine or cholinesterase inhibitors is
      effective in treating some of these symptoms. However, the role of cholinergic
      transmission in motor stereotypy remains unknown. During strong cocaine-induced
      motor stereotypy, we showed earlier that increased dopamine release results in
      decreased acetylcholine release in the territory of the dorsal striatum related
      to the prefrontal cortex. Here, we investigated the role of striatal cholinergic
      transmission in the arrest of motor stereotypy. Analysis of N-methyl-d-aspartic
      acid-evoked release of dopamine and acetylcholine during declining intensity of
      motor stereotypy revealed a dissociation between dopamine and acetylcholine
      release. Whereas dopamine release remained increased, the inhibition of
      acetylcholine release decreased, mirroring the time course of motor stereotypy.
      Furthermore, pharmacological treatments restoring striatal acetylcholine release
      (raclopride, dopamine D2 antagonist; intraperitoneal or local injection in
      prefrontal territory of the dorsal striatum) rapidly stopped motor stereotypy. In
      contrast, pharmacological treatments that blocked the post-synaptic effects of
      acetylcholine (scopolamine, muscarinic antagonist; intraperitoneal or striatal
      local injection) or induced degeneration of cholinergic interneurons (AF64A,
      cholinergic toxin) in the prefrontal territory of the dorsal striatum robustly
      prolonged the duration of strong motor stereotypy. Thus, we propose that
      restoration of cholinergic transmission in the prefrontal territory of the dorsal
      striatum plays a key role in the arrest of motor stereotypy.

PMID- 21097494
TI  - Origin and evolution of a novel DnaA-like plasmid replication type in
      Rhodobacterales.
AB  - Large extrachromosomal elements are widespread among Alphaproteobacteria, but it
      is unclear how up to a dozen low-copy plasmids can stably coexist within the same
      cell. We systematically analyzed the distribution of different replicons in about
      40 completely sequenced genomes of the Roseobacter clade (Rhodobacterales) and
      surprisingly identified a novel plasmid replicon type. The conserved replication
      module comprises the characteristic partitioning operon (parAB) and a hitherto
      unknown replicase. The latter shows a weak homology to the chromosomal
      replication initiator DnaA and was accordingly named "DnaA-like." Phylogenetic
      analyses of the adjacent parAB genes document a common ancestry with repA- and
      repB-type plasmids and moreover indicate the presence of two dnaA-like
      compatibility groups. This conclusion is supported by conserved palindrome
      sequences within the replication module that probably represent crucial
      centromeric anchors for plasmid partitioning. The functionality of dnaA-like
      replicons was proven by transformation experiments in Phaeobacter gallaeciensis
      BS107 (DSM 17395). This Roseobacter strain furthermore allows the phenotypical
      monitoring of plasmid incompatibility, based on a 262-kb dnaA-like replicon
      required for the brown pigmentation of the bacterium. Uptake of an incompatible
      construct induces its loss, hence resulting in white colonies. Accordingly, we
      could substantiate the in silico predictions about stable maintenance of dnaA
      like plasmids and thereby functionally validate our approach of plasmid
      classification based on phylogenetic analyses.

PMID- 21097495
TI  - Thermus thermophilus glycoside hydrolase family 57 branching enzyme: crystal
      structure, mechanism of action, and products formed.
AB  - Branching enzyme (EC 2.4.1.18; glycogen branching enzyme; GBE) catalyzes the
      formation of alpha1,6-branching points in glycogen. Until recently it was
      believed that all GBEs belong to glycoside hydrolase family 13 (GH13). Here we
      describe the cloning and expression of the Thermus thermophilus family GH57-type
      GBE and report its biochemical properties and crystal structure at 1.35-A
      resolution. The enzyme has a central (beta/alpha)(7)-fold catalytic domain A with
      an inserted domain B between beta2 and alpha5 and an alpha-helix-rich C-terminal
      domain, which is shown to be essential for substrate binding and catalysis. A
      maltotriose was modeled in the active site of the enzyme which suggests that
      there is insufficient space for simultaneously binding of donor and acceptor
      substrates, and that the donor substrate must be cleaved before acceptor
      substrate can bind. The biochemical assessment showed that the GH57 GBE possesses
      about 4% hydrolytic activity with amylose and in vitro forms a glucan product
      with a novel fine structure, demonstrating that the GH57 GBE is clearly different
      from the GH13 GBEs characterized to date.

PMID- 21097496
TI  - Cytotoxic enhancement of a bispecific diabody by format conversion to tandem
      single-chain variable fragment (taFv): the case of the hEx3 diabody.
AB  - Diabodies (Dbs) and tandem single-chain variable fragments (taFv) are the most
      widely used recombinant formats for constructing small bispecific antibodies.
      However, only a few studies have compared these formats, and none have discussed
      their binding kinetics and cross-linking ability. We previously reported the
      usefulness for cancer immunotherapy of a humanized bispecific Db (hEx3-Db) and
      its single-chain format (hEx3-scDb) that target epidermal growth factor receptor
      and CD3. Here, we converted hEx3-Db into a taFv format to investigate how format
      affects the function of a small bispecific antibody; our investigation included a
      cytotoxicity assay, surface plasmon resonance spectroscopy, thermodynamic
      analysis, and flow cytometry. The prepared taFv (hEx3-taFv) showed an enhanced
      cytotoxicity, which may be attributable to a structural superiority to the
      diabody format in cross-linking target cells but not to differences in the
      binding affinities of the formats. Comparable cross-linking ability for soluble
      antigens was observed among hEx3-Db, hEx3-scDb, and hEx3-taFv with surface
      plasmon resonance spectroscopy. Furthermore, drastic increases in cytotoxicity
      were found in the dimeric form of hEx3-taFv, especially when the two hEx3-taFv
      were covalently linked. Our results show that converting the format of small
      bispecific antibodies can improve their function. In particular, for small
      bispecific antibodies that target tumor and immune cells, a functional
      orientation that avoids steric hindrance in cross-linking two target cells may be
      important in enhancing the growth inhibition effect.

PMID- 21097497
TI  - Transcriptional activation of the cAMP-responsive modulator promoter in human T
      cells is regulated by protein phosphatase 2A-mediated dephosphorylation of SP-1
      and reflects disease activity in patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous
      abnormalities recorded at the cellular, molecular, and genetic level. Expression
      of the basic leucine zipper transcription factor cAMP-responsive element
      modulator (CREM)alpha was reported to be abnormally increased in T cells from SLE
      patients. CREMalpha suppresses IL-2 and T cell receptor zeta chain gene
      transcription by direct binding to the respective promoters. Here, we show that
      increased CREM expression is the result of enhanced promoter activity. DNA
      binding analyses reveal direct binding of transcription factor specificity
      protein-1 (SP-1) to the CREM promoter resulting in enhanced transcriptional
      activity and increased CREM expression. Protein phosphatase 2A is known to
      activate SP-1 through dephosphorylation at its serine residue 59. Our results
      show that nuclei from SLE T cells contain lower levels of Ser(59)-phosphorylated
      SP-1 protein and a stronger SP-1 binding to the CREM promoter. We conclude that
      protein phosphatase 2A accounts for enhanced SP-1 dephosphorylation at Ser(59) in
      SLE T cells. More importantly, CREM promoter activity mirrors reliably disease
      activity in SLE patients, underscoring its potential role as a biomarker for the
      prediction of flares in SLE patients.

PMID- 21097498
TI  - Negative regulation of the endocytic adaptor disabled-2 (Dab2) in mitosis.
AB  - Mitotic cells undergo extensive changes in shape and size through the altered
      regulation and function of their membrane trafficking machinery. Disabled 2
      (Dab2), a multidomain cargo-specific endocytic adaptor and a mediator of signal
      transduction, is a potential integrator of trafficking and signaling. Dab2 binds
      effectors of signaling and trafficking that localize to different intracellular
      compartments. Thus, differential localization is a putative regulatory mechanism
      of Dab2 function. Furthermore, Dab2 is phosphorylated in mitosis and is thus
      regulated in the cell cycle. However, a detailed description of the intracellular
      localization of Dab2 in the different phases of mitosis and an understanding of
      the functional consequences of its phosphorylation are lacking. Here, we show
      that Dab2 is progressively displaced from the membrane in mitosis. This
      phenomenon is paralleled by a loss of co-localization with clathrin. Both
      phenomena culminate in metaphase/anaphase and undergo partial recovery in
      cytokinesis. Treatment with 2-methoxyestradiol, which arrests cells at the
      spindle assembly checkpoint, induces the same effects observed in metaphase
      cells. Moreover, 2-methoxyestradiol also induced Dab2 phosphorylation and reduced
      Dab2/clathrin interactions, endocytic vesicle motility, clathrin exchange
      dynamics, and the internalization of a receptor endowed with an NPXY endocytic
      signal. Serine/threonine to alanine mutations, of residues localized to the
      central region of Dab2, attenuated its phosphorylation, reduced its membrane
      displacement, and maintained its endocytic abilities in mitosis. We propose that
      the negative regulation of Dab2 is part of an accommodation of the cell to the
      altered physicochemical conditions prevalent in mitosis, aimed at allowing
      endocytic activity throughout the cell cycle.

PMID- 21097499
TI  - Conservation and diversification of dileucine signal recognition by adaptor
      protein (AP) complex variants.
AB  - The clathrin-associated, heterotetrameric adaptor protein (AP) complexes, AP-1,
      AP-2, and AP-3, recognize signals in the cytosolic domains of transmembrane
      proteins, leading to their sorting to endosomes, lysosomes, lysosome-related
      organelles, and/or the basolateral membrane of polarized epithelial cells. One
      type of signal, referred to as "dileucine-based," fits the consensus motif
      (D/E)XXXL(L/I). Previous biochemical analyses showed that (D/E)XXXL(L/I) signals
      bind to a combination of two subunits of each AP complex, namely the AP-1 gamma
      sigma1, AP-2 alpha-sigma2, and AP-3 delta-sigma3 hemicomplexes, and structural
      studies revealed that an imperfect variant of this motif lacking the (D/E)
      residue binds to a site straddling the interface of alpha and sigma2. Herein, we
      report mutational and binding analyses showing that canonical (D/E)XXXL(L/I)
      signals bind to this same site on AP-2, and to similar sites on AP-1 and AP-3.
      The strength and amino acid requirements of different interactions depend on the
      specific signals and AP complexes involved. We also demonstrate the occurrence of
      diverse AP-1 heterotetramers by combinatorial assembly of various gamma and
      sigma1 subunit isoforms encoded by different genes. These AP-1 variants bind
      (D/E)XXXL(L/I) signals with marked preferences for certain sequences, implying
      that they are not functionally equivalent. Our results thus demonstrate that
      different AP complexes share a conserved binding site for (D/E)XXXL(L/I) signals.
      However, the characteristics of the binding site on each complex vary, providing
      for the specific recognition of a diverse repertoire of (D/E)XXXL(L/I) signals.

PMID- 21097500
TI  - SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in
      Xenopus laevis oocytes.
AB  - The SLC36 family of transporters consists of four genes, two of which, SLC36A1
      and SLC36A2, have been demonstrated to code for human proton-coupled amino acid
      transporters or hPATs. Here we report the characterization of the fourth member
      of the family, SLC36A4 or hPAT4, which when expressed in Xenopus laevis oocytes
      also encodes a plasma membrane amino acid transporter, but one that is not proton
      coupled and has a very high substrate affinity for the amino acids proline and
      tryptophan. hPAT4 in Xenopus oocytes mediated sodium-independent, electroneutral
      uptake of [(3)H]proline, with the highest rate of uptake when the uptake medium
      pH was 7.4 and an affinity of 3.13 MUM. Tryptophan was also an excellently
      transported substrate with a similarly high affinity (1.72 MUM). Other amino
      acids that inhibited [(3)H]proline were isoleucine (K(i) 0.23 mM), glutamine
      (0.43 mM), methionine (0.44 mM), and alanine (1.48 mM), and with lower affinity,
      glycine, threonine, and cysteine (K(i) >5 mM for all). Of the amino acids
      directly tested for transport, only proline, tryptophan, and alanine showed
      significant uptake, whereas glycine and cysteine did not. Of the non-proteogenic
      amino acids and drugs tested, only sarcosine produced inhibition (K(i) 1.09 mM),
      whereas gamma-aminobutyric acid (GABA), beta-alanine, L-Dopa, D-serine, and delta
      aminolevulinic acid were without effect on [(3)H]proline uptake. This
      characterization of hPAT4 as a very high affinity/low capacity non-proton-coupled
      amino acid transporter raises questions about its physiological role, especially
      as the transport characteristics of hPAT4 are very similar to the Drosophila
      orthologue PATH, an amino acid "transceptor" that plays a role in nutrient
      sensing.

PMID- 21097501
TI  - Myristoylation of cGMP-dependent protein kinase dictates isoform specificity for
      serotonin transporter regulation.
AB  - By transporting serotonin (5-HT) into neurons and other cells, serotonin
      transporter (SERT) modulates the action of 5-HT at cell surface receptors. SERT
      itself is modulated by several processes, including the cGMP signaling pathway.
      Activation of SERT by cGMP requires the cGMP-dependent protein kinase (PKG). Here
      we show that in HeLa cells lacking endogenous PKG, expression of PKGIalpha or
      PKGIbeta was required for 8-bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP)
      to stimulate SERT phosphorylation and 5-HT influx. Catalytically inactive PKG
      mutants and wild-type PKGII did not support this stimulation. However, a mutant
      PKGII (G2A) that was not myristoylated substituted for functional PKGI,
      suggesting that myristoylation and subsequent membrane association blocked
      productive interaction with SERT. PKG also influenced SERT expression and
      localization. PKGI isoforms increased total and cell surface SERT levels, and
      PKGII decreased cell surface SERT without altering total expression. Remarkably,
      these changes did not require 8-Br-cGMP or functional kinase activity and were
      also observed with a SERT mutant resistant to activation by PKG. Both PKGIalpha
      and PKGIbeta formed detergent-stable complexes with SERT, and this association
      did not require catalytic activity. The nonmyristoylated PKGII G2A mutant
      stimulated SERT expression similar to PKGI isoforms. These results suggest
      multiple mechanisms by which PKG can modulate SERT and demonstrate that the
      functional difference between PKG isoforms results from myristoylation of PKGII.

PMID- 21097502
TI  - Regulation of glial glutamate transporters by C-terminal domains.
AB  - Excitatory amino acid transporter 2 (EAAT2) is a high affinity glutamate
      transporter predominantly expressed in astroglia. Human EAAT2 encompasses eight
      transmembrane domains and a 74-amino acid C-terminal domain that resides in the
      cytoplasm. We examined the role of this region by studying various C-terminal
      truncations and mutations using heterologous expression in mammalian cells, whole
      cell patch clamp recording and confocal imaging. Removal of the complete C
      terminus (K498X EAAT2) results in loss of function because of intracellular
      retention of truncated proteins in the cytoplasm. However, a short stretch of
      amino acids (E500X EAAT2) within the C terminus results in correctly processed
      transporters. E500X reduced glutamate transport currents by 90%. Moreover, the
      voltage and substrate dependence of E500X EAAT2 anion currents was significantly
      altered. WT and mutant EAAT2 anion channels are modified by external Na(+) in the
      presence as well as in the absence of L-glutamate. Whereas Na(+) stimulates EAAT2
      anion currents in the presence of L-glutamate, increased [Na(+)] reduces such
      currents without glutamate. In cells internally dialyzed with Na(+), WT, and
      truncated EAAT2 display comparable Na(+) dependence. With K(+) as main internal
      cation, E500X drastically increased the apparent dissociation constant for
      external Na(+). The effects of E500X can be represented by a kinetic model that
      allows translocation of the empty transporter from the outward- to the inward
      facing conformation and stabilization of the inward-facing conformation by
      internal K(+). Our results demonstrate that the C terminus modifies the glutamate
      uptake cycle, possibly affecting the movements of the translocation domain of
      EAAT2 glutamate transporter.

PMID- 21097503
TI  - UNC93B1 is essential for TLR11 activation and IL-12-dependent host resistance to
      Toxoplasma gondii.
AB  - Toll-like receptor (TLR) activation relies on biochemical recognition of
      microbial molecules and localization of the TLR within specific cellular
      compartments. Cell surface TLRs largely recognize bacterial membrane components,
      and intracellular TLRs are exclusively involved in sensing nucleic acids. Here we
      show that TLR11, an innate sensor for the Toxoplasma protein profilin, is an
      intracellular receptor that resides in the endoplasmic reticulum. The 12 membrane
      spanning endoplasmic reticulum-resident protein UNC93B1 interacts directly with
      TLR11 and regulates the activation of dendritic cells in response to Toxoplasma
      gondii profilin and parasitic infection in vivo. A deficiency in functional
      UNC93B1 protein abolished TLR11-dependent IL-12 secretion by dendritic cells,
      attenuated Th1 responses against T. gondii, and dramatically enhanced
      susceptibility to the parasite. Our results reveal that the association with
      UNC93B1 and the intracellular localization of TLRs are not unique features of
      nucleic acid-sensing TLRs but is also essential for TLR11-dependent recognition
      of T. gondii profilin and for host protection against this parasite.

PMID- 21097504
TI  - AlphaB-crystallin is found in detergent-resistant membrane microdomains and is
      secreted via exosomes from human retinal pigment epithelial cells.
AB  - alphaB-crystallin (alphaB) is known as an intracellular Golgi membrane-associated
      small heat shock protein. Elevated levels of this protein have been linked with a
      myriad of neurodegenerative pathologies including Alzheimer disease, multiple
      sclerosis, and age-related macular degeneration. The membrane association of
      alphaB has been known for more than 3 decades, yet its physiological import has
      remained unexplained. In this investigation we show that alphaB is secreted from
      human adult retinal pigment epithelial cells via microvesicles (exosomes),
      independent of the endoplasmic reticulum-Golgi protein export pathway. The
      presence of alphaB in these lipoprotein structures was confirmed by its
      susceptibility to digestion by proteinase K only when exosomes were exposed to
      Triton X-100. Transmission electron microscopy was used to localize alphaB in
      immunogold-labeled intact and permeabilized microvesicles. The saucer-shaped
      exosomes, with a median diameter of 100-200 nm, were characterized by the
      presence of flotillin-1, alpha-enolase, and Hsp70, the same proteins that
      associate with detergent-resistant membrane microdomains (DRMs), which are known
      to be involved in their biogenesis. Notably, using polarized adult retinal
      pigment epithelial cells, we show that the secretion of alphaB is predominantly
      apical. Using OptiPrep gradients we demonstrate that alphaB resides in the DRM
      fraction. The secretion of alphaB is inhibited by the cholesterol-depleting drug,
      methyl beta-cyclodextrin, suggesting that the physiological function of this
      protein and the regulation of its export through exosomes may reside in its
      association with DRMs/lipid rafts.

PMID- 21097505
TI  - The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA
      155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1).
AB  - Macrophages play a central role in the balance and efficiency of the immune
      response and are at the interface between innate and adaptive immunity. Their
      phenotype is a delicate equilibrium between the M1 (classical, pro-Th(1)) and M2
      (alternative, pro-Th(2)) profiles. This balance is regulated by cytokines such as
      interleukin 13 (IL-13), a typical pro-M2-Th(2) cytokine that has been related to
      allergic disease and asthma. IL-13 binds to IL-13 receptor alpha1 (IL13Ralpha1),
      a component of the Type II IL-4 receptor, and exerts its effects by activating
      the transcription factor signal transducer and activator of transcription 6
      (STAT6) through phosphorylation. MicroRNAs are short (~22 nucleotide) inhibitory
      non-coding RNAs that block the translation or promote the degradation of their
      specific mRNA targets. By bioinformatics analysis, we found that microRNA-155
      (miR-155) is predicted to target IL13Ralpha1. This suggested that miR-155 might
      be involved in the regulation of the M1/M2 balance in macrophages by modulating
      IL-13 effects. miR-155 has been implicated in the development of a healthy immune
      system and function as well as in the inflammatory pro-Th(1)/M1 immune profile.
      Here we have shown that in human macrophages, miR-155 directly targets
      IL13Ralpha1 and reduces the levels of IL13Ralpha1 protein, leading to diminished
      activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13
      dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE)
      involved in the establishment of an M2/pro-Th(2) phenotype in macrophages. Our
      work shows a central role for miR-155 in determining the M2 phenotype in human
      macrophages.

PMID- 21097506
TI  - Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila
      infection in human monocytes.
AB  - The ability of Legionella pneumophila to cause pneumonia is determined by its
      capability to evade the immune system and grow within human monocytes and their
      derived macrophages. Human monocytes efficiently activate caspase-1 in response
      to Salmonella but not to L. pneumophila. The molecular mechanism for the lack of
      inflammasome activation during L. pneumophila infection is unknown. Evaluation of
      the expression of several inflammasome components in human monocytes during L.
      pneumophila infection revealed that the expression of the apoptosis-associated
      speck-like protein (ASC) and the NOD-like receptor NLRC4 are significantly down
      regulated in human monocytes. Exogenous expression of ASC maintained the protein
      level constant during L. pneumophila infection and conveyed caspase-1 activation
      and restricted the growth of the pathogen. Further depletion of ASC with siRNA
      was accompanied with improved NF-kappaB activation and enhanced L. pneumophila
      growth. Therefore, our data demonstrate that L. pneumophila manipulates ASC
      levels to evade inflammasome activation and grow in human monocytes. By targeting
      ASC, L. pneumophila modulates the inflammasome, the apoptosome, and NF-kappaB
      pathway simultaneously.

PMID- 21097507
TI  - Tumor-secreted PGE2 inhibits CCL5 production in activated macrophages through
      cAMP/PKA signaling pathway.
AB  - One of the major characteristics of tumors is their ability to evade
      immunosurveillance through altering the properties and functions of host stromal
      and/or immune cells. CCL5 has been shown to play important roles in T cell
      proliferation, IFN-gamma, and IL-2 production, which promotes the differentiation
      and proliferation of Th1 cells important for immune defense against intracellular
      infection. In this study we found that tumor-bearing mice were more susceptible
      to bacterial infection and showed reduced CCL5 levels in serum during endotoxic
      shock. Our data further demonstrated that the soluble factors secreted by mammary
      gland tumor cells but not normal mammary gland epithelial cells inhibited CCL5
      expression in macrophages in response to LPS, but not to TNF-alpha stimulation.
      The inhibitory effect of tumor-secreted molecules on LPS-induced CCL5 expression
      was regulated at the post-transcriptional level. Blocking PGE(2) synthesis by
      NS398 or through the use of PGE(2) receptor antagonists AH-6809 (EP2 antagonist)
      and AH-23848 (EP4 antagonist) completely reversed the inhibitory effect of tumor
      conditioned medium (TCM) on LPS-induced CCL5 expression. Moreover, PGE(2) and the
      cAMP analog forskolin could mimic tumor-mediated CCL5 inhibition, and the
      inhibitory effects of TCM, PGE(2), and cAMP analog on LPS-induced CCL5 expression
      could be completely reversed by the PKA inhibitor H89. Furthermore, blocking
      PGE(2) synthesis in vivo led to partial recovery of CCL5 production during
      endotoxic shock. Taken together, our data indicate that PGE(2) secreted from
      breast cancer cells suppresses CCL5 secretion in LPS-activated macrophages
      through a cAMP/PKA signaling pathway, which may result in suppression of host
      immune responses against subsequent bacterial infection.

PMID- 21097508
TI  - A novel motif in the Crohn's disease susceptibility protein, NOD2, allows TRAF4
      to down-regulate innate immune responses.
AB  - The Crohn's disease and early onset sarcoidosis susceptibility protein, NOD2,
      coordinates innate immune signaling pathways. Because dysregulation of this
      coordination can lead to inflammatory disease, maintaining appropriate activation
      of the NOD2 signaling pathway is paramount in immunologic homeostasis. In this
      work, we identify the atypical tumor necrosis factor-associated factor (TRAF)
      family member, TRAF4, as a key negative regulator of NOD2 signaling. TRAF4
      inhibits NOD2-induced NF-kappaB activation and directly binds to NOD2 to inhibit
      NOD2-induced bacterial killing. We find that two consecutive glutamate residues
      in NOD2 are required for interaction with TRAF4 and inhibition of NOD2 signaling
      because mutation of these residues abrogated both TRAF4 binding and inhibition of
      NOD2. This work identifies a novel negative regulator of NOD2 signaling.
      Additionally, it defines a TRAF4 binding motif within NOD2 involved in
      termination of innate immune signaling responses.

PMID- 21097509
TI  - Altered immune response in mice deficient for the G protein-coupled receptor
      GPR34.
AB  - The X-chromosomal GPR34 gene encodes an orphan G(i) protein-coupled receptor that
      is highly conserved among vertebrates. To evaluate the physiological relevance of
      GPR34, we generated a GPR34-deficient mouse line. GPR34-deficient mice were
      vital, reproduced normally, and showed no gross abnormalities in anatomical,
      histological, laboratory chemistry, or behavioral investigations under standard
      housing. Because GPR34 is highly expressed in mononuclear cells of the immune
      system, mice were specifically tested for altered functions of these cell types.
      Following immunization with methylated BSA, the number of granulocytes and
      macrophages in spleens was significantly lower in GPR34-deficient mice as in wild
      type mice. GPR34-deficient mice showed significantly increased paw swelling in
      the delayed type hypersensitivity test and higher pathogen burden in
      extrapulmonary tissues after pulmonary infection with Cryptococcus neoformans
      compared with wild-type mice. The findings in delayed type hypersensitivity and
      infection tests were accompanied by significantly different basal and stimulated
      TNF-alpha, GM-CSF, and IFN-gamma levels in GPR34-deficient animals. Our data
      point toward a functional role of GPR34 in the cellular response to immunological
      challenges.

PMID- 21097510
TI  - DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator
      of NF-kappaB.
AB  - Heightened DJ-1 (Park7) expression is associated with a reduction in
      chemotherapeutic-induced cell death and poor prognosis in several cancers,
      whereas the loss of DJ-1 function is found in a subgroup of Parkinson disease
      associated with neuronal death. This study describes a novel pathway by which DJ
      1 modulates cell survival. Mass spectrometry shows that DJ-1 interacts with BBS1,
      CLCF1, MTREF, and Cezanne/OTUD7B/Za20d1. Among these, Cezanne is a known
      deubiquitination enzyme that inhibits NF-kappaB activity. DJ-1/Cezanne
      interaction is confirmed by co-immunoprecipitation of overexpressed and
      endogenous proteins, maps to the amino-terminal 70 residues of DJ-1, and leads to
      the inhibition of the deubiquitinating activity of Cezanne. Microarray profiling
      of shRNA-transduced cells shows that DJ-1 and Cezanne regulate IL-8 and ICAM-1
      expression in opposing directions. Similarly, DJ-1 enhances NF-kappaB nuclear
      translocation and cell survival, whereas Cezanne reduces these outcomes. Analysis
      of mouse Park7(-/-) primary cells confirms the regulation of ICAM-1 by DJ-1 and
      Cezanne. As NF-kappaB is important in cellular survival and transformation, IL-8
      functions as an angiogenic factor and pro-survival signal, and ICAM-1 has been
      implicated in tumor progression, invasion, and metastasis; these data provide an
      additional modality by which DJ-1 controls cell survival and possibly tumor
      progression via interaction with Cezanne.

PMID- 21097512
TI  - Proinflammatory role of let-7 miRNAs in experimental asthma?

PMID- 21097511
TI  - Alterations in postnatal neurogenesis and dopamine dysregulation in
      schizophrenia: a hypothesis.
AB  - An increasing number of studies demonstrate the important role of several
      susceptibility genes for schizophrenia, such as neuregulin-1 and DISC1, in early
      postnatal and adult neurogenesis. Its significance for the pathophysiology of the
      disease, including its relation to neurotransmitter systems implicated in
      schizophrenia (like the dopamine system), remains, however, unknown. Here, we
      review molecular and cellular components of the dopamine system associated with
      postnatal neurogenesis and plasticity, both in rodents and in primates, and
      discuss their possible implication in schizophrenia. We focus mainly on the
      islands of Calleja, complex aggregations of granule cells in the ventral
      striatum, generated early postnatally in the subventricular zone. In contrast to
      the involution of the primate olfactory bulb, the islands of Calleja attain their
      maximal development in humans, an evolution paralleled by a larger ventral
      subventricular zone and more connections with other structures, including
      temporal cortical areas. The islands of Calleja express high levels of neuronal
      nitric oxide (NO) synthase and D3 dopamine receptors and are densely
      interconnected by dopaminergic projections with the ventral tegmental area. D3
      receptors modulate subventricular zone neurogenesis and dopamine release. Their
      genetic deletion induces striatal hyperdopaminergia. We review data indicating a
      high plasticity of postnatal islands of Calleja, potentially facilitating
      susceptibility to schizophrenia-related risk factors. In this context, we propose
      a new pathophysiological model, where altered neurogenesis of the islands of
      Calleja may contribute to dysfunction of the dopamine and NO systems and
      psychosis through convergence of genetic and environmental disease-associated
      factors.

PMID- 21097514
TI  - Smoking patterns in cancer survivors.
AB  - INTRODUCTION: More than 11 million cancer survivors are at risk for new cancers,
      yet many are receiving inadequate guidance to reduce their risk. This study
      describes smoking trends among a group of cancer survivors (CaSurvivors) compared
      with a no cancer (NoCancer) control group. METHODS: The Health Information
      National Trends Survey 2003, 2005, and 2007 cross-sectional surveys were used in
      this secondary data analysis. Descriptive statistics were produced, and logistic
      regressions of current smokers were performed on weighted samples using SUDAAN.
      The sample included 2,060 CaSurvivors; the average age was 63 years; and the
      majority of respondents were female (67%), White (80.6%), married, or partnered
      (52.5%), with at least some college education (57%). The mean time since
      diagnosis was 12 years; 28.7% reported fair or poor health status. RESULTS: The
      overall smoking rate was 18.7% for CaSurvivors and 21.7% for the NoCancer group.
      Education (less than college), age (younger), marital status (widowed or
      divorced), and health care access (none or partial) were significant personal
      variables associated with a greater likelihood of being a current smoker.
      Controlling for these variables, there were no differences between the
      CaSurvivors and NoCancer groups over time. Women with cervical cancer were still
      more likely to be smokers (48.9%) than other CaSurvivors (p < .001). CONCLUSIONS:
      CaSurvivors' current smoking trends were similar to the control group. While most
      variation was explained by demographic variables, women with cervical cancer, a
      smoking-related cancer, had the highest prevalence of smoking. Smoking cessation
      interventions should be targeted to this high-risk group.

PMID- 21097517
TI  - Neurovascular coupling in the human visual cortex is modulated by cyclooxygenase
      1 (COX-1) gene variant.
AB  - Functional hyperemia, the brain's capability to alter microvascular blood flow in
      response to the metabolic demands of active neurons, is essential for sustained
      mammalian brain function. Pharmacological studies in mice suggest neurovascular
      coupling to centrally involve cyclooxygenase-1 (COX-1) metabolites such as
      prostaglandins. In humans, however, genetic variation of the COX-1 gene impacting
      the coupling of neural activity to hemodynamic responses (HRs) has not been
      investigated yet. In this study, we determined whether COX-1 genotype-dependent
      enzymatic function impacts HRs in humans. Specifically, using a double-blind
      Imaging Genetics approach utilizing functional near-infrared spectroscopy, we
      measured HRs following visual checkerboard stimulation. COX-1 genotype (L237M,
      rs5789)-dependent decrease in enzymatic function in heterozygous L/M carriers is
      associated with a 42% reduction of the HR amplitude. This finding is discussed in
      the context of potentially imbalanced neurovascular mechanisms involving
      arachidonic acid, which underlie vasodilatory and vasoconstrictive forces of
      functional hemodynamics. Generally, these findings might help to improve our
      understanding of pathologies such as stroke and Alzheimer's disease in which
      neurovascular coupling is altered. Additionally, our results may have important
      implications for functional brain imaging in which HRs are commonly used as a
      surrogate for neural activation.

PMID- 21097516
TI  - Three systems of insular functional connectivity identified with cluster
      analysis.
AB  - Despite much research on the function of the insular cortex, few studies have
      investigated functional subdivisions of the insula in humans. The present study
      used resting-state functional connectivity magnetic resonance imaging (MRI) to
      parcellate the human insular lobe based on clustering of functional connectivity
      patterns. Connectivity maps were computed for each voxel in the insula based on
      resting-state functional MRI (fMRI) data and segregated using cluster analysis.
      We identified 3 insular subregions with distinct patterns of connectivity: a
      posterior region, functionally connected with primary and secondary somatomotor
      cortices; a dorsal anterior to middle region, connected with dorsal anterior
      cingulate cortex, along with other regions of a previously described control
      network; and a ventral anterior region, primarily connected with pregenual
      anterior cingulate cortex. Applying these regions to a separate task data set, we
      found that dorsal and ventral anterior insula responded selectively to disgusting
      images, while posterior insula did not. These results demonstrate that clustering
      of connectivity patterns can be used to subdivide cerebral cortex into
      anatomically and functionally meaningful subregions; the insular regions
      identified here should be useful in future investigations on the function of the
      insula.

PMID- 21097518
TI  - Molecular photoacoustic imaging of angiogenesis with integrin-targeted gold
      nanobeacons.
AB  - Photoacoustic tomography (PAT) combines optical and acoustic imaging to generate
      high-resolution images of microvasculature. Inherent sensitivity to hemoglobin
      permits PAT to image blood vessels but precludes discriminating neovascular from
      maturing microvasculature. alpha(v)beta(3)-Gold nanobeacons (alpha(v)beta(3)
      GNBs) for neovascular molecular PAT were developed, characterized, and
      demonstrated in vivo using a mouse Matrigel-plug model of angiogenesis. PAT
      results were microscopically corroborated with fluorescent alpha(v)beta(3)-GNB
      localization and supporting immunohistology in Rag1(tm1Mom) Tg(Tie-2-lacZ)182
      Sato mice. alpha(v)beta(3)-GNBs (154 nm) had 10-fold greater contrast than blood
      on an equivolume basis when imaged at 740 nm to 810 nm in blood. The lowest
      detectable concentration in buffer was 290 nM at 780 nm. Noninvasive PAT of
      angiogenesis using a 10-MHz ultrasound receiver with alpha(v)beta(3)-GNBs
      produced a 600% increase in signal in a Matrigel-plug mouse model relative to the
      inherent hemoglobin contrast pretreatment. In addition to increasing the contrast
      of neovessels detected at baseline, alpha(v)beta(3)-GNBs allowed visualization of
      numerous angiogenic sprouts and bridges that were undetectable before contrast
      injection. Competitive inhibition of alpha(v)beta(3)-GNBs with alpha(v)beta(3)
      NBs (no gold particles) almost completely blocked contrast enhancement to
      pretreatment levels, similar to the signal from animals receiving saline only.
      Consistent with other studies, nontargeted GNBs passively accumulated in the
      tortuous neovascular but provided less than half of the contrast enhancement of
      the targeted agent. Microscopic studies revealed that the vascular constrained,
      rhodamine-labeled alpha(v)beta(3)-GNBs homed specifically to immature
      neovasculature (PECAM(+), Tie-2(-)) along the immediate tumor periphery, but not
      to nearby mature microvasculature (PECAM(+), Tie-2(+)). The combination of PAT
      and alpha(v)beta(3)-GNBs offered sensitive and specific discrimination and
      quantification of angiogenesis in vivo, which may be clinically applicable to a
      variety of highly prevalent diseases, including cancer and cardiovascular
      disease.

PMID- 21097521
TI  - In defence of exercise stress tests for the diagnosis of pulmonary hypertension.

PMID- 21097522
TI  - Fenestrated Amplatzer atrial septal defect occluder in an elderly patient with
      restrictive left ventricular physiology.

PMID- 21097519
TI  - Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral
      circadian gene expression in nonhuman primates.
AB  - The effect of in utero exposure to a maternal high-fat diet on the peripheral
      circadian system of the fetus is unknown. Using mRNA copy number analysis, we
      report that the components of the peripheral circadian machinery are transcribed
      in the nonhuman primate fetal liver in an intact phase-antiphase fashion and that
      Npas2, a paralog of the Clock transcription factor, serves as the rate-limiting
      transcript by virtue of its relative low abundance (10- to 1000-fold lower). We
      show that exposure to a maternal high-fat diet in utero significantly alters the
      expression of fetal hepatic Npas2 (up to 7.1-fold, P<0.001) compared with that in
      control diet-exposed animals and is reversible in fetal offspring from obese dams
      reversed to a control diet (1.3-fold, P>0.05). Although the Npas2 promoter
      remains largely unmethylated, differential Npas2 promoter occupancy of
      acetylation of fetal histone H3 at lysine 14 (H3K14ac) occurs in response to
      maternal high-fat diet exposure compared with control diet-exposed animals.
      Furthermore, we find that disruption of Npas2 is consistent with high-fat diet
      exposure in juvenile animals, regardless of in utero diet exposure. In summary,
      the data suggest that peripheral Npas2 expression is uniquely vulnerable to diet
      exposure.

PMID- 21097520
TI  - Tyrosine phosphorylation controls nuclear export of Fyn, allowing Nrf2 activation
      of cytoprotective gene expression.
AB  - Fyn, an Src kinase family member, acts as a negative regulator of NF-E2-related
      factor 2 (Nrf2). Under stressful conditions, Nrf2 translocates into the nucleus
      and binds to the antioxidant response element (ARE), activating defensive gene
      expression. Once Nrf2 completes activation, Fyn phosphorylates tyrosine 568 of
      Nrf2, resulting in the nuclear export and degradation of Nrf2. The present
      studies demonstrate that within 0.5 h of antioxidant treatment in human
      hepatoblastoma (HepG2) cells, Fyn exports out of the nucleus, allowing Nrf2
      unimpeded movement to the ARE. Mutation of tyrosine 213 of Fyn stymied nuclear
      export, suggesting that tyrosine phosphorylation controls nuclear export. Mass
      spectrometry confirmed tyrosine 213 as the site of phosphorylation. ChIP and real
      time PCR assays revealed that FynY213A mutant caused decreased binding of Nrf2 to
      the promoter of defensive gene NAD(P)H:quinone oxidoreductase 1 (NQO1) and
      decreased NQO1 expression by 5-fold (P<0.0001) compared to wild-type Fyn. In
      addition, a putative nuclear export signal (NES) was identified, and mutation of
      it also inhibited nuclear export of Fyn. Furthermore, FynY213A caused an
      increased susceptibility to cell death following treatment with etoposide in
      mouse hepatoma (Hepa-1) cells. The preinduction regulation of Nrf2 is controlled
      by the nuclear export of Fyn, allowing for activation of defensive gene
      expression.

PMID- 21097523
TI  - Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce
      airway inflammation via a reactive oxygen species-dependent pathway.
AB  - Group 2 allergen of Dermatophagoides pteronyssinus 2 (Der p2) induces airway
      inflammation without protease activity, and elevated nerve growth factor (NGF)
      levels are also found in this inflammation. How the allergen Der p2 regulates NGF
      release via reactive oxygen species (ROS) to induce inflammation remains unclear.
      In the present study, intratracheal administration of Der p2 to mice led to
      inflammatory cell infiltration, mucus gland hyperplasia, and NGF upregulation in
      the bronchial epithelium, as well as elevated ROS and NGF production in
      bronchoalveolar lavage fluids. In addition, Der p2 caused fibrocyte accumulation
      and mild fibrosis. p38 mitogen-activated protein kinase (MAPK) and c-Jun N
      terminal kinase (JNK) inhibitors inhibited Der p2-induced NGF release in LA4 lung
      epithelial cells and MLg lung fibroblasts. Pretreatment with an antioxidant,
      tiron, reduced the Der p2-induced ROS production, NGF expression and release, p38
      MAPK or JNK phosphorylation, and airway inflammation. These results suggest that
      Der p2 allergen-induced airway inflammation and elevated NGF release were through
      increasing ROS production and a MAPK-dependent pathway. The use of an
      antioxidant, tiron, may provide a new therapeutic modality for the treatment of
      allergic asthma.

PMID- 21097524
TI  - TNF/TNFR1 signaling mediates doxorubicin-induced diaphragm weakness.
AB  - Doxorubicin, a common chemotherapeutic agent, causes respiratory muscle weakness
      in both patients and rodents. Tumor necrosis factor-alpha (TNF), a
      proinflammatory cytokine that depresses diaphragm force, is elevated following
      doxorubicin chemotherapy. TNF-induced diaphragm weakness is mediated through TNF
      type 1 receptor (TNFR1). These findings lead us to hypothesize that TNF/TNFR1
      signaling mediates doxorubicin-induced diaphragm muscle weakness. We tested this
      hypothesis by treating C57BL/6 mice with a clinical dose of doxorubicin (20
      mg/kg) via intravenous injection. Three days later, we measured contractile
      properties of muscle fiber bundles isolated from the diaphragm. We tested the
      involvement of TNF/TNFR1 signaling using pharmaceutical and genetic
      interventions. Etanercept, a soluble TNF receptor, and TNFR1 deficiency protected
      against the depression in diaphragm-specific force caused by doxorubicin.
      Doxorubicin stimulated an increase in TNFR1 mRNA and protein (P < 0.05) in the
      diaphragm, along with colocalization of TNFR1 to the plasma membrane. These
      results suggest that doxorubicin increases diaphragm sensitivity to TNF by
      upregulating TNFR1, thereby causing respiratory muscle weakness.

PMID- 21097525
TI  - Selective eicosanoid-generating capacity of cytoplasmic phospholipase A2 in
      Pseudomonas aeruginosa-infected epithelial cells.
AB  - Airway neutrophil infiltration is a pathological hallmark observed in multiple
      lung diseases including pneumonia and cystic fibrosis. Bacterial pathogens such
      as Pseudomonas aeruginosa instigate neutrophil recruitment to the air space.
      Excessive accumulation of neutrophils in the lung often contributes to tissue
      destruction. Previous studies have unveiled hepoxilin A(3) as the key molecular
      signal driving neutrophils across epithelial barriers. The eicosanoid hepoxilin
      A(3) is a potent neutrophil chemoattractant produced by epithelial cells in
      response to infection with P. aeruginosa. The enzyme phospholipase A(2) liberates
      arachidonic acid from membrane phospholipids, the rate-limiting step in the
      synthesis of all eicosanoids, including hepoxilin A(3). Once generated,
      aracidonic acid is acted upon by multiple cyclooxygenases and lipoxygenases
      producing an array of functionally diverse eicosanoids. Although there are
      numerous phospholipase A(2) isoforms capable of generating arachidonic acid, the
      isoform most often associated with eicosanoid generation is cytoplasmic
      phospholipase A(2)alpha. In the current study, we observed that the cytoplasmic
      phospholipase A(2)alpha isoform is required for mediating P. aeruginosa-induced
      production of certain eicosanoids such as prostaglandin E(2). However, we found
      that neutrophil transepithelial migration induced by P. aeruginosa does not
      require cytoplasmic phospholipase A(2)alpha. Furthermore, P. aeruginosa-induced
      hepoxilin A(3) production persists despite cytoplasmic phospholipase A(2)alpha
      suppression and generation of the 12-lipoxygenase metabolite 12-HETE is actually
      enhanced in this context. These results suggest that alterative phospholipase
      A(2) isoforms are utilized to synthesize 12-lipoxygenase metabolites. The
      therapeutic implications of these findings are significant when considering anti
      inflammatory therapies based on targeting eicosanoid synthesis pathways.

PMID- 21097526
TI  - Caveolin-1: a critical regulator of lung injury.
AB  - Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal
      structural component of caveolae. Cav-1 regulates critical cell functions
      including proliferation, apoptosis, cell differentiation, and transcytosis via
      diverse signaling pathways. Abundant in almost every cell type in the lung,
      including type I epithelial cells, endothelial cells, smooth muscle cells,
      fibroblasts, macrophages, and neutrophils, cav-1 plays a crucial role in the
      pathogenesis of acute lung injury (ALI). ALI and its severe form, acute
      respiratory distress syndrome (ARDS), are responsible for significant morbidity
      and mortality in intensive care units, despite improvement in ventilation
      strategies. The pathogenesis of ARDS is still poorly understood, and therapeutic
      options remain limited. In this article, we summarize recent data regarding the
      regulation and function of cav-1 in lung biology and pathology, in particular as
      it relates to ALI. We further discuss the potential molecular and cellular
      mechanisms by which cav-1 expression contributes to ALI. Investigating the
      cellular functions of cav-1 may provide new insights for understanding the
      pathogenesis of ALI and provide novel targets for therapeutic interventions in
      the future.

PMID- 21097528
TI  - Micronuclei levels in peripheral blood lymphocytes as a potential biomarker for
      pancreatic cancer risk.
AB  - To find biomarkers for risk prediction of pancreatic cancer (PC), we evaluated
      the frequency of micronuclei (MN) in peripheral lymphocytes of 346 patients with
      PC and 449 healthy controls. The levels of baseline MN (mean +/- standard error
      of micronucleated cells per 1000 binucleated cells) were significantly higher in
      patients (15.3 +/- 0.3) than those in controls [9.7 +/- 0.5; adjusted for body
      mass index (BMI), P < 0.001]. Using the median levels found in controls as the
      cut point, 78.9% of patients and 43.7% of controls had a higher frequency of MN.
      Logistic regression analysis with adjustment for known risk factors for PC showed
      that having a higher level of MN was significantly associated with increased risk
      of PC [odds ratio (OR): 8.32, 95% confidence interval (CI): 5.06-13.67, P <
      0.001]; and the risk was much higher in men than in women [OR (95% CI): 14.19
      (7.09-28.40) versus 4.19 (1.90-9.27)]. The level of MN was not associated with
      disease stage or resection status but was related to smoking status in men and to
      BMI in women among patients. The level of MN was higher in smokers (14.5 +/- 0.6)
      than in nonsmokers (12.1 +/- 0.6; P = 0.023) and in obese (25.3 +/- 2.8) versus
      normal weight individuals (17.7 +/- 0.8; P = 0.024). These data showed that
      elevated level of MN in peripheral lymphocytes was associated with increased risk
      of PC.

PMID- 21097527
TI  - MCP-1/CCR2B-dependent loop upregulates MUC5AC and MUC5B in human airway
      epithelium.
AB  - Cigarette smoke represents a major risk factor for the development of chronic
      obstructive pulmonary disease (COPD), a respiratory condition associated with
      airflow obstruction, mucus hypersecretion, chronic inflammation, and upregulation
      of inflammatory mediators such as the monocyte chemotactic protein-1 (MCP-1). MCP
      1 through its receptor CCR2 induces chemotaxis and activates (44/42)MAPK, a
      kinase known to play a key role in mucin regulation in bronchial epithelium. In
      the present study we used differentiated primary cultures of normal human
      bronchial epithelial (NHBE) cells to test whether MCP-1 through its receptor CCR2
      induces mucin upregulation. We have provided evidence that NHBE cells release MCP
      1 to the epithelial surface and express the CCR2B isoform of the receptor mainly
      at the apical pole. In addition, we found that MCP-1 has a novel function in
      airway epithelium, increasing the two major airway mucins MUC5AC and MUC5B, an
      effect mediated, at least in part, by a cascade of events initiated by
      interaction of its receptor CCR2B with G(q) subunits in caveolae, followed by
      PLCbeta, PKC, and (44/42)MAPK activation. We also have shown that MCP-1 is able
      to induce its own expression using the same receptor but through a different
      pathway that involves RhoA GTPase. Furthermore, we found that a single exposure
      to MCP-1 is enough to induce MCP-1 secretion and sustained mucin upregulation up
      to 7 days after initial exposure, an effect mediated by CCR2B as confirmed using
      short hairpin RNA. These results agree with our data in smoker's airway
      epithelium, where CCR2B is present in MUC5AC- and MUC5B-expressing cells and
      augmented MCP-1 expression is associated with increased MUC5AC and MUC5B
      immunolabeling, suggesting that the mechanisms described in primary cell cultures
      in the present study are operative in vivo. Therefore, therapeutic approaches
      targeting MCP-1/CCR2B may be useful in preventing not only influx of inflammatory
      cells to the airways but also mucus hypersecretion and goblet cell hyperplasia.

PMID- 21097529
TI  - L1-CAM expression in ccRCC correlates with shorter patients survival times and
      confers chemoresistance in renal cell carcinoma cells.
AB  - Conflicting data exist about the expression of L1 cell adhesion molecule (L1-CAM)
      in clear cell renal cell carcinoma (ccRCC). To determine the clinical usefulness
      of L1-CAM as a therapeutic or prognostic marker molecule in renal cancer
      patients, we analyzed its expression on a cohort of 282 renal cell carcinoma
      (RCC) patients. L1-CAM expression was found in 49.5% of 282 renal cancer tissues.
      Importantly, L1-CAM expression in patients with ccRCC was associated with
      significantly shorter patient survival time. We further present evidence that L1
      CAM was involved in the resistance against therapeutic reagents like rapamycin,
      sunitinib and cisplatin. The downregulation of L1-CAM expression decreased renal
      cancer cell proliferation and reduced the expression of cyclin D1. In addition,
      we found out that Von Hippel-Lindau (VHL) deficiency was accompanied by a
      downregulation of the transcription factor PAX8 and L1-CAM. In normal renal
      tissue, PAX8 and L1-CAM were co-expressed in collecting duct cells. Importantly,
      the downregulation of PAX8 by small interfering RNA increased the expression of
      L1-CAM and concomitantly induced the migration of renal cancer cells.
      Furthermore, we observed in 65.3% of 282 RCC patients a downregulation of PAX8
      expression. With chromatin immunoprecipitation analysis, we additionally
      demonstrate that PAX8 can bind to the promoter of L1-CAM and we further observed
      that the downregulation of PAX8 was accompanied by increased L1-CAM expression in
      a high fraction of ccRCC patients. In summary, we show that VHL and PAX8 are
      involved in the regulation of L1-CAM in renal cancer and L1-CAM represents an
      important therapeutic and prognostic marker protein for the treatment of ccRCC.

PMID- 21097530
TI  - Influence of GSTM1, GSTT1, GSTP1, NAT1, NAT2, EPHX1, MTR and MTHFR polymorphism
      on chromosomal aberration frequencies in human lymphocytes.
AB  - We have studied the influence of genetic polymorphisms in the xenobiotic
      metabolizing genes GSTM1, GSTP1, GSTT1, EPHX1, NAT1 and NAT2 and the folate
      metabolizing genes MTR and MTHFR on the frequencies of cells with chromosomal
      aberrations (CAs) in peripheral lymphocytes of Norwegian men. Log-linear Poisson
      regression models were applied on 357 subjects of whom data on all the
      polymorphisms examined were available. Total CAs and chromosome-type aberrations
      (CSAs) were significantly increased by higher age alone, whereas chromatid-type
      aberrations (CTAs) were elevated by the GSTT1-null genotype and MTHFR codon 222
      variant allele and chromatid gaps (CTGs) by EPHX1 high activity genotype and
      occupational exposure. Stratification by smoking and age (<40 and >=40 years)
      showed that the effect of the GSTT1 null and EPHX1 high activity genotypes only
      concerned (older) smokers, in agreement with the roles of the respective enzymes
      in detoxification and metabolic activation. The MTHFR codon 222 variant allele
      was associated with high CTGs in smokers, the MTR codon 919 variant allele with
      high CTAs in older smokers and the NAT2 fast acetylator genotype with high CTGs
      in older subjects. Among younger nonsmokers, however, carriers of the MTHFR codon
      222 and MTR codon 919 variant alleles showed a decrease in the level of CTGs and
      total CAs, respectively. In conclusion, polymorphisms of GSTT1, EPHX1, MTHFR, MTR
      and NAT2 differentially affect the frequency of CTAs, CSAs and CTGs, showing
      interaction with smoking and age. It appears that CA subtypes rather than total
      CAs should be considered in this type of studies.

PMID- 21097534
TI  - Shear bond strength after multiple bracket bonding with or without repeated
      etching.
AB  - The purpose of the study was to measure the in vitro shear bond strength (SBS) of
      metal brackets after multiple bonding and debonding with and without repeated
      etching. One hundred and twenty extracted premolars were divided into three equal
      groups. In group 1, the brackets were bonded and debonded three times with
      repeated enamel etching and in groups 2 and 3 without repeated etching. In group
      2, all composite remnants were removed before bonding, while in group 3, the
      remnants were levelled. Analysis of variance was used to determine significant
      differences in SBS with Bonferroni adjustment for the multiple testing
      procedures. The results showed that in group 1, the mean SBS was 11.69 MPa (SD
      2.65) at the first, 14.30 MPa (SD 2.69) at the second, and 12.19 MPa (SD 2.26) at
      the third debonding. In group 2, SBS decreased from 12.57 MPa (SD 2.54) to below
      8.0 MPa. In group 3, SBS remained constant from the first (11.93 MPa; SD 2.14) to
      the second (12.06 MPa; SD 1.65) debonding and only decreased significantly to
      9.74 MPa (SD 1.80) at the third debonding. Less composite remained on the teeth
      after each debonding sequence. This was characterized by a shift from adhesive
      remnant index (ARI) scores 2 and 3 after the first debonding to ARI scores 1 and
      2 after the second debonding to predominantly scores 0 and 1 after the third
      debonding. After bracket loss and levelling of composite remnants, the SBS is
      sufficient for application of orthodontic forces. Repeated etching may involve a
      higher risk of enamel tear-outs during debonding.

PMID- 21097531
TI  - Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach
      tumor development and progression in tumor suppressor-deficient mouse strains.
AB  - Zinc deficiency is associated with high incidences of esophageal and other
      cancers in humans and leads to a highly proliferative hyperplastic condition in
      the upper gastrointestinal tract in laboratory rodents. Zn replenishment reduces
      the incidence of lingual, esophageal and forestomach tumors in Zn-deficient rats
      and mice. While previous animal studies focused on Zn deficiency, we have
      investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient
      mice of wild-type and tumor suppressor-deficient mouse strains. All mice received
      N-nitrosomethylbenzylamine and half the mice of each strain then received Zn
      supplementation. At killing, mice without Zn supplementation had developed more
      tumors than Zn-supplemented mice: wild-type C57BL/6 mice developed an average of
      7.0 versus 5.0 tumors for Zn supplemented (P < 0.05); Zn-supplemented Fhit-/-
      mice averaged 5.7 versus 8.0 for control mice (P < 0.01); Zn-supplemented Fhit-/
      Nit1-/- mice averaged 5.4 versus 9.2 for control mice (P < 0.01) and Zn
      supplemented Fhit-/-Rassf1a-/- (the murine gene) mice averaged 5.9 versus 9.1 for
      control mice (P < 0.01). Zn supplementation reduced tumor burdens by 28% (wild
      type) to 42% (Fhit-/-Nit1-/-). Histological analysis of forestomach tissues also
      showed significant decreases in severity of preneoplastic and neoplastic lesions
      in Zn-supplemented cohorts of each mouse strain. Thus, Zn supplementation
      significantly reduced tumor burdens in mice with multiple tumor suppressor
      deficiencies. When Zn supplementation was begun at 7 weeks after the final
      carcinogen dose, the reduction in tumor burden was the same as observed when
      supplementation began immediately after carcinogen dosing, suggesting that Zn
      supplementation may affect tumor progression rather than tumor initiation.

PMID- 21097535
TI  - Correspondence in relation to critical appraisal by Chapman et al.

PMID- 21097536
TI  - An unusual case of refractory asthma.

PMID- 21097538
TI  - Single maintenance and reliever therapy (SMART) of asthma.

PMID- 21097537
TI  - Single maintenance and reliever therapy.

PMID- 21097540
TI  - Hyaline vascular Castleman disease relapsing as T cell rich B cell lymphoma with
      paraneoplastic pemphigus.

PMID- 21097541
TI  - Fine needle aspiration cytology is a valuable adjunct to axillary ultrasound in
      the preoperative staging of breast cancer.
AB  - AIMS: To compare the predictive values of axillary ultrasound (US) combined with
      fine needle aspiration (FNA) cytology with tumour size (T stage) and grade in the
      preoperative staging of breast cancer. More precise definition of axillary FNA
      reporting nomenclature is also presented. PATIENTS AND METHODS: 314 patients: 119
      patients had suspicious US investigated by FNA, 195 patients had normal US not
      investigated further preoperatively. This study examined the node-positive and
      node-negative cases in these two groups, calculating predictive values for
      cytology, US, T stage and tumour grade, and tested comparisons for significance.
      RESULTS: Axillary FNA has a positive predictive value of 84.8% compared with US
      (66.7%). The difference is significant (p=0.008). Negative US has a negative
      predictive value of 81.0% compared with a negative predictive value for cytology
      of 66.7%, but the difference is not significant (p=0.08). 43% of patients with
      unsatisfactory cytology were node positive. Of 195 patients with negative
      axillary US, 37 (19%) had metastatic nodal disease. Fewer than 20% of these
      patients had micrometastases alone. Tumour size and grade influenced node status
      in US-suspicious cases only. CONCLUSION: Axillary FNA adds significantly to the
      positive predictive value provided by US. US gives false-negative results in 19%
      of cases and only a small proportion of these can be explained by
      micrometastases. Unsatisfactory cytology needs to be repeated because of a high
      rate of positive nodes in this group.

PMID- 21097542
TI  - High-mannose glycans are elevated during breast cancer progression.
AB  - Alteration in glycosylation has been observed in cancer. However, monitoring
      glycosylation changes during breast cancer progression is difficult in humans. In
      this study, we used a well-characterized transplantable breast tumor mouse model,
      the mouse mammary tumor virus-polyoma middle T antigen, to observe early changes
      in glycosylation. We have previously used the said mouse model to look at O
      linked glycosylation changes with breast cancer. In this glycan biomarker
      discovery study, we examined N-linked glycan variations during breast cancer
      progression of the mouse model but this time doubling the number of mice and
      blood draw points. N-glycans from total mouse serum glycoproteins were profiled
      using matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron
      resonance mass spectrometry at the onset, progression, and removal of mammary
      tumors. We observed four N-linked glycans, m/z 1339.480 (Hex(3)HexNAc), 1485.530
      (Hex(3)HexNAc(4)Fuc), 1809.639 (Hex(5)HexNAc(4)Fuc), and 1905.630 (Man(9)),
      change in intensity in the cancer group but not in the control group. In a
      separate study, N-glycans from total human serum glycoproteins of breast cancer
      patients and controls were also profiled. Analysis of human sera using an
      internal standard showed the alteration of the low-abundant high-mannose glycans,
      m/z 1419.475, 1581.528, 1743.581, 1905.634 (Man(6-9)), in breast cancer patients.
      A key observation was the elevation of a high-mannose type glycan containing nine
      mannoses, Man(9), m/z 1905.630 in both mouse and human sera in the presence of
      breast cancer, suggesting an incompletion of the glycosylation process that
      normally trims back Man(9) to produce complex and hybrid type oligosaccharides.

PMID- 21097544
TI  - Managing non-response rates for the National Child Safety Seat Survey in Canada.
AB  - BACKGROUND: Canada has a Road Safety Vision of having the safest roads in the
      world, yet vehicle crashes have remained the leading cause of death of Canadian
      children for a number of years. OBJECTIVES: Determine the influence of high rates
      of non-participation on the estimates for correct use of safety seats for child
      occupants in vehicles. Examine the impact of three different criteria for
      determining correct safety seat use on the estimates of correct use of safety
      seats for children in Canada. METHODS: A national child seat safety survey was
      conducted in 200 randomly selected sites across Canada that included both
      naturalistic observation of child seat safety use at intersections and a detailed
      vehicle inspection in nearby parking lots. Non-participation in the detailed
      parking lot study was high. This study reports on statistical methods for
      managing high rates of non-response and compared estimates of correct use using
      three different criteria. RESULTS AND CONCLUSIONS: Results revealed that high non
      participation rates introduced bias into the raw estimates of correct safety seat
      use. Correct use estimates also varied substantially depending on which criterion
      (more stringent or less stringent) for correct use was applied in the analysis.
      When child age was the only criterion for correct use, estimates were higher than
      when more stringent criteria of child height and weight were applied to estimate
      rates of correct use. This study identifies the importance of managing high rates
      of non-response in safety seat observation studies using statistical techniques.
      Stringent criteria for correct use may provide more accurate estimates of the
      correct use of safety seats. Studies of child seat use in vehicles (using
      voluntary participation) may benefit from the use of naturalistic observation to
      capture non-participants' use of child occupant restraints, as it may more
      accurately estimate the rates of correct use in populations.

PMID- 21097545
TI  - Reversible heart failure: the role of inflammatory activation.
AB  - Heart failure is increasingly common in western populations and is an inevitable
      consequence of the improved survival after myocardial infarction, and of an
      ageing population. Heart failure is usually relentlessly progressive as the
      maladaptive processes triggered by the physiological changes of the condition
      lead to further deterioration. However, in certain circumstances, heart failure
      is transient or potentially reversible when it occurs as part of intense systemic
      inflammatory activation. This review considers the role of inflammation in the
      aetiology of heart failure, and illustrates the strategies which have been used
      to modify the inflammatory response with anonymised clinical case reports.

PMID- 21097543
TI  - Identification of phosphoproteins associated with human neutrophil granules
      following chemotactic peptide stimulation.
AB  - Regulated exocytosis of neutrophil intracellular storage granules is necessary
      for neutrophil participation in the inflammatory response. The signal
      transduction pathways that participate in neutrophil exocytosis are complex and
      poorly defined. Several protein kinases, including p38 MAPK and the nonreceptor
      tyrosine kinases, Hck and Fgr, participate in this response. However, the
      downstream targets of these kinases that regulate exocytosis are unknown. The
      present study combined a novel inhibitor of neutrophil exocytosis with proteomic
      techniques to identify phosphopeptides and phosphoproteins from a population of
      gelatinase and specific granules isolated from unstimulated and fMLF-stimulated
      neutrophils. To prevent loss of granule-associated phosphoproteins upon
      exocytosis, neutrophils were pretreated with a TAT-fusion protein containing a
      SNARE domain from SNAP-23 (TAT-SNAP-23), which inhibited fMLF-stimulated CD66b
      containing granule exocytosis by 100+/-10%. Following TAT-SNAP-23 pretreatment,
      neutrophils were stimulated with the chemotactic peptide fMLF for 0 min, 1 min,
      and 2 min. Granules were isolated by gradient centrifugation and subjected to
      proteolytic digestion with trypsin or chymotrypsin to obtain peptides from the
      outer surface of the granule. Phosphopeptides were enriched by gallium or TiO2
      affinity chromatography, and phosphopeptides and phosphorylation sites were
      identified by reversed phase high performance liquid chromatography-electrospray
      ionization-tandem MS. This resulted in the identification of 243 unique
      phosphopeptides corresponding to 235 proteins, including known regulators of
      vesicle trafficking. The analysis identified 79 phosphoproteins from resting
      neutrophils, 81 following 1 min of fMLF stimulation, and 118 following 2 min of
      stimulation. Bioinformatic analysis identified a potential Src tyrosine kinase
      motif from a phosphopeptide corresponding to G protein coupled receptor kinase 5
      (GRK5). Phosphorylation of GRK5 by Src was confirmed by an in vitro kinase
      reaction and by precursor ion scanning for phospho-tyrosine specific immonium
      ions containing Tyr251 and Tyr253. Immunoprecipitation of phosphorylated GRK5
      from intact cells was reduced by a Src inhibitor. In conclusion, targets of
      signal transduction pathways were identified that are candidates to regulate
      neutrophil granule exocytosis.

PMID- 21097546
TI  - Eye movements in amyotrophic lateral sclerosis and its mimics: a review with
      illustrative cases.
AB  - Abnormal eye movements are increasingly recognised in patients with amyotrophic
      lateral sclerosis (ALS) and, when they occur, may provide insights into the
      pattern and pathogenesis of the disease process. In patients with disorders that
      mimic ALS, abnormal eye movements may point to the correct diagnosis. In both of
      these circumstances, systematic examination of eye movements and interpretation
      of the findings with reference to modern concepts of their neural substrate will
      aid diagnosis and suggest pathogenesis. Here, key points with illustrative case
      histories and eye movement records are highlighted.

PMID- 21097547
TI  - Multimodal imaging reveals the role of gamma activity in eating-reflex seizures.
AB  - In reflex epilepsies, alteration of gamma oscillations may mediate transition
      between interictal and ictal states. Here, we explored a patient having seizures
      triggered by syrup intake. From intracranial electroencephalography combined with
      functional MRI, the overlap of the gustatory cortex and of the preictal and ictal
      onset zones, as defined by early gamma changes, motivated the successful
      resective surgery of the middle short gyrus of the right insula. This case
      provides a rare demonstration from human gamma activity that the route to seizure
      may be supported by the interplay between physiological and epileptogenic
      networks.

PMID- 21097548
TI  - Freud, neurology and the emergence of dynamic neural networks.

PMID- 21097550
TI  - Prior suggestive symptoms in one-third of patients consulting for a "first"
      demyelinating event.
AB  - OBJECTIVE: To evaluate the prevalence of prior inflammatory events in patients
      consulting for a first inflammatory neurological event and improve early
      diagnosis of multiple sclerosis. METHODS: During the initial visit, the
      neurologist gave patients a self-administered questionnaire containing 72
      questions regarding previous symptoms lasting >24 h. During the follow-up visit,
      the neurologist validated the symptoms and collected information about the
      current attack. RESULTS: The cohort included 178 patients (74% women, mean age
      (SD) 33.7 (10.1) years). The main reason for the initial visit was visual
      disturbance and sensory troubles in limbs. Mean (SD) global Expanded Disability
      Status Scale score was 1.4 (1.1), 46% of brains MRIs were positive according to
      Barkhof-Tintore criteria, 41% had abnormal white blood cell count in
      cerebrospinal fluid and 71% had immunoglobin G oligoclonal bands. Prior symptoms
      suggestive of demyelination were reported by 79 patients (44%), validated by the
      neurologist for 70% (55 patients) and identified only by the neurologist in four
      patients. Sequelae were observed in 14 patients with validated prior symptoms
      (26%). The self-administered questionnaire showed an overall sensitivity of 93%
      and specificity of 80% for identifying patients with prior symptoms suggestive of
      demyelination. CONCLUSION: A patient-administered questionnaire subsequently
      validated by the neurologist demonstrated that 33% of patients consulting for a
      first demyelinating event had prior symptoms suggestive of central nervous system
      demyelination that had gone unnoticed, and almost 70% had either sequelae of
      prior demyelination or McDonald criteria for dissemination in space. Such a
      questionnaire could be a useful tool for earlier diagnosis of multiple sclerosis.

PMID- 21097551
TI  - Alteration of nutritional status at diagnosis is a prognostic factor for survival
      of amyotrophic lateral sclerosis patients.
AB  - OBJECTIVES: The aims were to analyse changes in nutritional parameters from
      diagnosis of amyotrophic lateral sclerosis (ALS) to death and to assess their
      relationships with survival at the time of diagnosis and during follow-up.
      METHODS: 92 ALS patients were included and clinically assessed every 3 months
      (ALS functional rating scale, manual muscular testing, forced vital capacity,
      weight, BMI, percentage weight loss). Bioimpedance was performed to evaluate body
      composition (fat-free mass, fat mass and hydration status) and phase angle.
      Survival analyses were performed from diagnosis to death or censoring date using
      a Cox model. RESULTS: The evolution of nutritional parameters in ALS patients was
      marked by significant decreases in weight, BMI, fat-free mass and phase angle,
      and increased fat mass. The authors identified an adjusted 30% increased risk of
      death for a 5% decrease from usual weight at time of diagnosis (RR 1.30; 95% CI
      1.08 to 1.56). During follow-up, the authors identified adjusted 34% (95% CI 18%
      to 51%) and 24% (95% CI 13% to 36%) increased risks of death associated with each
      5% decrease in usual weight and each unit decrease in usual BMI, respectively
      (p<0.0001). Malnutrition during the course was related to a shorter survival
      (p=0.01), and fat mass level was associated with a better outcome (RR 0.90 for
      each 2.5 kg fat mass increment). CONCLUSIONS: Nutritional parameters of ALS
      patients worsened during evolution of the disease, and worse nutritional status
      (at time of diagnosis or during the course) was associated with a higher
      mortality. This study offers some justification for studying the use of
      therapeutic nutritional intervention to modify the survival of ALS patients.

PMID- 21097552
TI  - Is aging in place a resource for or risk to life satisfaction?
AB  - PURPOSE: Given age-related health restrictions, the importance of the environment
      for life satisfaction may increase in later life. This study investigated whether
      objective and perceived physical and social environmental aspects of the home and
      of the surrounding neighborhood represent resources for or risks to life
      satisfaction among young-old and old-old individuals. DESIGN AND METHODS: A
      population-based sample of 381 community-dwelling individuals aged 65-94 years
      reported on their sociophysical environment and life satisfaction using
      questionnaires. RESULTS: On average, young-old differ from old-old in indoor
      physical environmental indicators but not in neighborhood characteristics or
      social aspects of housing. Regression analyses revealed that apartment size,
      perceived neighborhood quality, and outdoor place attachment explained life
      satisfaction independently, whereas social housing aspects played only a minor
      role. Separate analyses for both age groups revealed age differential explanation
      patterns. Apartment size was positively related to life satisfaction in the young
      old but was negatively related in the old-old. For the old-old, perceived
      neighborhood quality and outdoor place attachment were more important than for
      the young-old. Living with others was positively related to life satisfaction
      only for the young-old.  IMPLICATIONS: Environmental characteristics at home and
      in the neighborhood need to be considered to better understand differential
      processes of aging in place with respect to well-being.

PMID- 21097553
TI  - Social network type and subjective well-being in a national sample of older
      Americans.
AB  - PURPOSE: The study considers the social networks of older Americans, a population
      for whom there have been few studies of social network type. It also examines
      associations between network types and well-being indicators: loneliness,
      anxiety, and happiness. DESIGN AND METHODS: A subsample of persons aged 65 years
      and older from the first wave of the National Social Life, Health, and Aging
      Project was employed (N = 1,462). We applied K-means cluster analysis to derive
      social network types using 7 criterion variables. In the multivariate stage, the
      well-being outcomes were regressed on the network type construct and on
      background and health characteristics by means of logistic regression. RESULTS:
      Five social network types were derived: "diverse," "friend," "congregant,"
      "family," and "restricted." Social network type was found to be associated with
      each of the well-being indicators after adjusting for demographic and health
      confounders. Respondents embedded in network types characterized by greater
      social capital tended to exhibit better well-being in terms of less loneliness,
      less anxiety, and greater happiness. IMPLICATIONS: Knowledge about differing
      network types should make gerontological practitioners more aware of the varying
      interpersonal milieus in which older people function. Adopting network type
      assessment as an integral part of intake procedures and tracing network shifts
      over time can serve as a basis for risk assessment as well as a means for
      determining the efficacy of interventions.

PMID- 21097554
TI  - Concomitant trastuzumab with thoracic radiotherapy: a morphological and
      functional study.
AB  - BACKGROUND: The purpose of this study is to elucidate if there is an additive or
      supra-additive toxic effects of radiotherapy (RT) and trastuzumab (T) on vascular
      structures when used concomitantly. METHODS: Female Wistar albino rats were
      treated with either 8 or 15 Gy of thoracic RT. T was applied i.p. with a dose of
      6 mg/kg 2 h before RT. Four rats in each arm were killed at 6th h, 21st and 70th
      days after irradiation and thoracic aorta of each animal was dissected for
      electron microscopy. In addition, functional studies for evaluating the
      relaxation and contraction were carried out 21 days after RT. RESULTS: Only 15-Gy
      RT dose groups showed significant difference in terms of functional deterioration
      as more contraction than the others (P < 0.05) without any difference between RT
      and RT + T. However, T produced additional deficit in relaxation when added to
      RT, which was considered near significant (P: 0.0502). Electron microscopy showed
      endothelial and subendotelial damage signs in 15-Gy dose groups. T + 15-Gy arm
      showed more pronounced endothelial cell damage than 15-Gy RT-only arm, 70 days
      after RT. CONCLUSION: T and high-dose RT may lead to vascular damage that seems
      at least additive.

PMID- 21097555
TI  - Ligand-induced conformational capture of a synthetic tetracycline riboswitch
      revealed by pulse EPR.
AB  - RNA aptamers are in vitro-selected binding domains that recognize their
      respective ligand with high affinity and specificity. They are characterized by
      complex three-dimensional conformations providing preformed binding pockets that
      undergo conformational changes upon ligand binding. Small molecule-binding
      aptamers have been exploited as synthetic riboswitches for conditional gene
      expression in various organisms. In the present study, double electron-electron
      resonance (DEER) spectroscopy combined with site-directed spin labeling was used
      to elucidate the conformational transition of a tetracycline aptamer upon ligand
      binding. Different sites were selected for post-synthetic introduction of either
      the (1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl) methanethiosulfonate by
      reaction with a 4-thiouridine modified RNA or of 4-isocyanato-2,6
      tetramethylpiperidyl-N-oxid spin label by reaction with 2'-aminouridine modified
      RNA. The results of the DEER experiments indicate the presence of a thermodynamic
      equilibrium between two aptamer conformations in the free state and capture of
      one conformation upon tetracycline binding.

PMID- 21097559
TI  - The continuing need to investigate the nature and content of teleconsultation
      communication using interaction analysis techniques.
AB  - The lack of systematically collected and analysed data about the effect of
      telemedicine on patient-provider communication is a frequently cited barrier for
      why video communication has yet to reach its full potential. Existing research
      provides little information about the subtle and detailed changes in
      communication that take place over video. Comprehensive investigations of actual
      medical encounter behaviour are therefore required, including verbal content
      analysis, which uses interaction analysis systems (IAS) to describe and
      categorize the communication that has taken place. Ten IAS studies were
      identified in the literature. Although it is difficult to generalize due to
      differences in methodology and context, some tentative conclusions can be drawn.
      First, on-site providers tend to be substantially less active than off-site
      providers, suggesting that the former typically serve as facilitators and
      observers, rather than active participants. Second, just as in the conventional
      face-to-face setting, providers' utterances tend to predominate in telemedicine.
      Third, conventional patterns of more task-focused than socio-emotional utterances
      tend to persist in telemedicine. However, some studies found telemedicine to be
      more patient-centred than conventional medicine, and others found it less so. We
      do not yet have a full understanding of the subtractive and enhancing effects of
      telemedicine on provider-patient relations and outcomes.

PMID- 21097556
TI  - Tandem affinity purification combined with inducible shRNA expression as a tool
      to study the maturation of macromolecular assemblies.
AB  - Tandem affinity purification (TAP) is an efficient method for the purification
      and characterization of large macromolecular complexes. To elucidate the role of
      specific components of such complexes, it is important to address the question of
      how loss of a specific factor affects complex composition. Here, we introduce a
      method that combines TAP of large macromolecular assemblies with inducible shRNA
      mediated protein depletion in human somatic cells. As a proof of principle, we
      have applied this method to the purification of human pre-ribosomal particles.
      Using inducible expression of ribosome assembly factors as bait proteins,
      different pre-40S particles could be isolated and characterized, revealing high
      conservation of the ribosome biogenesis pathway from yeast to human cells.
      Besides known ribosome maturation factors, C21orf70 was identified as a novel pre
      40S component. By combining TAP of pre-40S particles with shRNA-mediated
      depletion of the pre-40S-associated protein kinase Rio2, we observed that
      increased levels of the nuclear HEAT-repeat protein Rrp12 are associated with 40S
      precursors in absence of Rio2. Further analyses revealed that Rrp12 is partially
      mislocalized to the cytoplasm and trapped on late 40S precursors upon loss of
      Rio2, and therefore fails to efficiently recycle to the nucleus. Thus, the
      combination of tandem affinity purification and shRNA induction provided further
      insights into late cytoplasmic 40S maturation steps, demonstrating the high
      potential of this method.

PMID- 21097560
TI  - Telerehabilitation in stroke care--a systematic review.
AB  - We conducted a systematic review of telerehabilitation interventions in stroke
      care. The following databases were searched: Medline, Embase, DARE-NHSEED-HTA
      (INAHTA) and the Cochrane Library. Nine studies, all published after 2000, were
      included in the review. A wide variety of telemedicine interventions in post
      stroke rehabilitation care was identified. Four studies had been carried out in
      the USA, two in the Netherlands, two in Italy and one in China. There were four
      randomized controlled trials and one qualitative analysis. Four studies used an
      observational study design/case series. Home-based telerehabilitation
      interventions showed promising results in improving the health of stroke patients
      and in supporting caregivers. Telemedicine systems based on a virtual environment
      for upper extremity exercise can improve the physical health of stroke patients.
      Health professionals and participants reported high levels of satisfaction and
      acceptance of telerehabilitation interventions. There was no evidence regarding
      the effects on resource utilization or cost-effectiveness. Most studies showed
      promising results, although overall, the quality of the evidence on
      telerehabilitation in post-stroke care was low.

PMID- 21097561
TI  - A pilot teleconsultation network for retinal diseases in ophthalmology.
AB  - A store-and-forward teleconsultation network was developed as a web application
      in order to provide second opinions on retinal diseases. The system provided
      automatic notification messages to the referring doctor and the consulted
      ophthalmologist by mobile phone message (SMS) and email. Images in the electronic
      medical record (EMR) could be examined in detail using special magnification
      software. Of the 19 ophthalmologists who agreed to participate, 17 used the
      teleconsultation network during the pilot trial (89%). During the four-week study
      period, a total of 52 EMRs containing 82 images were uploaded by the
      participating ophthalmologists. In 46 cases (89%), a second opinion was provided
      by the consulted ophthalmologist. Thirty-three of the cases (72%) were related to
      macular diseases and anti-VEGF (vascular endothelial growth factor) ophthalmology
      drugs. At the end of the study period, 18 of the participating ophthalmologists
      evaluated the cases, using a three-point score (poor, good, very good) for
      Access, Acceptability, Image Quality and Medical Efficacy. Most cases were rated
      as very good or good for all four variables. Successful use of the network in
      future will depend on various technical, policy and human factors. The latter is
      particularly important and appropriate motivations need to be found in order to
      promote teleconsultations.

PMID- 21097562
TI  - Effectiveness and safety of telemedical management in uncomplicated urinary tract
      infections.
AB  - Uncomplicated urinary tract infections (UUTI) in women are frequent reasons for
      consultations in general practice. We evaluated the effectiveness and safety of
      telemedical management at a telemedicine centre in Switzerland. Management
      followed evidence-based protocols, including teleprescription of an antibiotic.
      Consecutive UUTI patients who had a teleconsultation including the prescription
      of an antibiotic were followed up three days later about symptom relief, adverse
      events or the need to visit a doctor. Of a total of 526 eligible women, follow-up
      information was available for 95%. Three days after teleconsultation, 79% of
      patients reported complete symptom relief, and 92% reported a reduction of UUTI
      symptoms. Five percent of patients reported deterioration, e.g. due to an
      increase of pain, flank pain or fever. Four percent reported side-effects of the
      prescribed antibiotics. In the three days following teleconsultation, 4% of women
      consulted another health-care provider without further contacting the
      telemedicine centre. Another 8% of patients were referred to face-to-face
      consultation because they developed additional symptoms or because bacterial
      resistance of the prescribed antibiotic was suspected. Compared to data from the
      literature on UUTI, evidence-based telemedical management including
      teleprescription of an antibiotic is as safe and effective as prescriptions
      initiated by a face-to-face consultation.

PMID- 21097563
TI  - Key challenges in the development and implementation of telehealth projects.
AB  - A literature review was carried out to identify the key challenges in the
      implementation of telehealth. This was followed by a survey of organisations in
      England involved in telehealth projects in order to understand the challenges
      they faced. Ten of the 13 health or local authority organisations surveyed had
      telehealth projects and three were at the planning stage. The analysis revealed
      seven key challenges facing implementers of telehealth in England. Based on the
      findings from the literature review and the survey, a model was constructed and a
      checklist drawn up. The model contained the following elements: identifying
      issues, needs and partners; producing a strategy; securing funding; implementing
      changes; and monitoring and evaluating a telehealth project. The checklist was
      validated by using key informants from the organisations originally surveyed. The
      checklist may be useful to guide telehealth development and implementation in the
      future.

PMID- 21097564
TI  - Systematic review of studies on telemonitoring of patients with congestive heart
      failure: a meta-analysis.
AB  - We conducted a systematic review of large, well-conducted randomised trials
      designed to evaluate the effectiveness of telemonitoring on patients with
      congestive heart failure (CHF). Two people reviewed 125 articles independently
      and selected 13 articles for final review. These studies concerned 3480 patients.
      The follow-up period of the studies was 3-15 months. Pooled estimate results
      showed that there was an overall reduction in all-cause mortality (P = 0.02).
      There was no overall reduction in all-cause hospital admission (P = 0.84),
      although there was a reduction in CHF hospital admission (P = 0.0004). There was
      no reduction in all-cause emergency admission (P = 0.67). There was no
      significant difference in length of stay in hospital, medication adherence or
      cost. Telemonitoring in conjunction with nurse home visiting and specialist unit
      support can be effective in the clinical management of patients with CHF and help
      to improve their quality of life.

PMID- 21097565
TI  - A review of the use of mobile phone text messaging in clinical and healthy
      behaviour interventions.
AB  - We reviewed the literature on the use of text messaging for clinical and healthy
      behaviour interventions. Electronic databases were searched in December 2009
      using keywords related to text messaging and health interventions. The final
      review included 24 articles. Of those, seven covered medication adherence, eight
      discussed clinical management and nine reported on health-related behaviour
      modification. Sixteen were randomized controlled trials (RCT), five were non
      controlled pre-post comparison studies and three were feasibility pilots not
      reporting a behavioural outcome. The frequency of messaging ranged from multiple
      messages daily to one message per month. Among the 16 RCTs, 10 reported
      significant improvement with interventions and six reported differences
      suggesting positive trends. Text messaging received good acceptance and showed
      early efficacy in most studies. However, the evidence base is compromised by
      methodological limitations and is not yet conclusive.

PMID- 21097549
TI  - Observing Huntington's disease: the European Huntington's Disease Network's
      REGISTRY.

PMID- 21097566
TI  - Delivery of Internet-based cancer genetic counselling services to patients'
      homes: a feasibility study.
AB  - We examined the feasibility of home videoconferencing for providing cancer
      genetic education and risk information to people at risk. Adults with possible
      hereditary colon or breast and ovarian cancer syndromes were offered Internet
      based counselling. Participants were sent web cameras and software to install on
      their home PCs. They watched a prerecorded educational video and then took part
      in a live counselling session with a genetic counsellor. A total of 31
      participants took part in Internet counselling sessions. Satisfaction with
      counselling was high in all domains studied, including technical (mean 4.3 on a 1
      5 scale), education (mean 4.7), communication (mean 4.8), psychosocial (mean 4.1)
      and overall (mean 4.2). Qualitative data identified technical aspects that could
      be improved. All participants reported that they would recommend Internet-based
      counselling to others. Internet-based genetic counselling is feasible and
      associated with a high level of satisfaction among participants.

PMID- 21097567
TI  - A pilot study of the Tele-Airway Management System in a hospital emergency
      department.
AB  - We developed a telemedicine system for remote guidance of emergency airway
      management called the Tele-Airway Management System (TAMS). In a pilot study we
      examined the usefulness of the TAMS for intubations of actual patients in a
      hospital emergency department. Twenty-five patients were allocated randomly
      either to a TAMS group or to an on-scene directed (OSD) group. A total of 12 were
      intubated using the TAMS. The mean time to intubation (TAMS 62 s vs. OSD 56 s)
      and the success rate was not different between the two groups (P > 0.05). There
      were two oesophageal intubations in the TAMS group and four in the OSD group, but
      this was not significantly different (P = 0.36). There were no mechanical or
      technical errors such as disconnection during use of the TAMS. The pilot study
      demonstrated the feasibility of the TAMS as an alternative to OSD. However, a
      larger study will be required to determine non-superiority or equivalence.

PMID- 21097568
TI  - VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a
      marker of progression in the follow-up of patients with differentiated thyroid
      carcinoma.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1)
      are known to be related to thyroid tumorigenesis. The aim of the study was to
      examine the expressions and serum levels of VEGF, VEGFR1, IGF1, and IGF1 receptor
      (IGF1R) in patients with differentiated thyroid carcinoma (DTC) compared with
      patients with nodular goiter (NG). METHODS: We examined 39 patients with DTC who
      had a clinical history of at least 2 years and compared them with 25 patients who
      had a pathological diagnosis of NG after thyroidectomy. Serum VEGF, VEGFR1, and
      IGF1 levels were measured in both patient groups. The expressions of VEGF,
      VEGFR1, IGF1, and IGF1R were analyzed by the immunohistochemical method in the
      paraffin blocks of patients' thyroidectomy samples of the patients. RESULTS: The
      immunostainings scores for VEGF, VEGFR1, IGF1, and IGF1R were found to be higher
      in patients with DTC than in those with NG. Only VEGFR1 expression was related to
      lymph node metastasis at the time of surgery. None of the expressions were
      related to the long-term prognosis of the patients. Serum VEGF was found to be
      higher in patients with progressive DTC than in patients in clinical remission.
      CONCLUSION: The expressions of VEGF and VEGFR1 were shown to be correlated with
      the expression of IGF1 and IGF1R. VEGFR1 expression may be an important index for
      the presence of lymph node metastasis at the time of thyroidectomy. Increased
      serum levels of VEGF may reflect disease recurrence in DTC.

PMID- 21097569
TI  - Danish children born with glutamic acid decarboxylase-65 and islet antigen-2
      autoantibodies at birth had an increased risk to develop type 1 diabetes.
AB  - OBJECTIVE: A large, population-based case-control cohort was used to test the
      hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2
      autoantibodies (IA-2A) at birth predict type 1 diabetes. DESIGN AND METHODS: The
      design was an individually matched case-control study of all Danish type 1
      diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004
      (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5
      days after birth in the 1981-2002 birth cohorts and stored at -25  degrees C were
      identified from 2023 patients and from two matched controls (n = 4042). Birth
      data and information on parental age and diabetes were obtained from Danish
      registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1
      alleles were analyzed by PCR using time-resolved fluorescence. RESULTS: GAD65A
      and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%)
      controls resulting in a hazard ratio (HR) of 7.49 (P < 0.0001). The HR decreased
      to 4.55 but remained significant (P < 0.0003) after controlling for parental
      diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a
      HR of 2.55 (P < 0.0001) for every tenfold increase in the levels of GAD65A and IA
      2A. This HR decreased to 1.93 but remained significant (P < 0.001) after
      controlling for parental diabetes and HLA-DQB1 alleles. CONCLUSION: These data
      suggest that GAD65A and IA-2A positivity at birth are associated with an
      increased risk of developing type 1 diabetes in Danish children diagnosed between
      1981 and 2004.

PMID- 21097570
TI  - Implantable cardioverter defibrillators after acute myocardial infarction.

PMID- 21097571
TI  - Managing frostbite.

PMID- 21097572
TI  - Prescribing and monitoring lithium therapy: summary of a safety report from the
      National Patient Safety Agency.

PMID- 21097575
TI  - New charity hopes to provide cheap pulse oximeters to hospitals in poor
      countries.

PMID- 21097577
TI  - Isolation and characterization of Shigella flexneri G3, capable of effective
      cellulosic saccharification under mesophilic conditions.
AB  - A novel Shigella strain (Shigella flexneri G3) showing high cellulolytic activity
      under mesophilic, anaerobic conditions was isolated and characterized. The
      bacterium is Gram negative, short rod shaped, and nonmotile and displays
      effective production of glucose, cellobiose, and other oligosaccharides from
      cellulose (Avicel PH-101) under optimal conditions (40 degrees C and pH 6.5).
      Approximately 75% of the cellulose was hydrolyzed in modified ATCC 1191 medium
      containing 0.3% cellulose, and the oligosaccharide production yield and specific
      production rate reached 375 mg g Avicel(-1) and 6.25 mg g Avicel(-1) h(-1),
      respectively, after a 60-hour incubation. To our knowledge, this represents the
      highest oligosaccharide yield and specific rate from cellulose for mesophilic
      bacterial monocultures reported so far. The results demonstrate that S. flexneri
      G3 is capable of rapid conversion of cellulose to oligosaccharides, with
      potential biofuel applications under mesophilic conditions.

PMID- 21097578
TI  - Characterization of glycoconjugates of extracellular polymeric substances in tufa
      associated biofilms by using fluorescence lectin-binding analysis.
AB  - Freshwater tufa deposits are the result of calcification associated with biofilms
      dominated by cyanobacteria. Recent investigations highlighted the fact that the
      formation of microbial calcium carbonates is mainly dependent on the saturation
      index, which is determined by pH, the ion activity of Ca(2+) and CO(3)(2-), and
      the occurrence of extracellular polymeric substances (EPS) produced by
      microorganisms. EPS, which contain carboxyl and/or hydroxyl groups, can strongly
      bind cations. This may result in inhibition of CaCO(3) precipitation. In
      contrast, the formation of templates for crystal nucleation was reported by many
      previous investigations. The purposes of this study were (i) to characterize the
      in situ distribution of EPS glycoconjugates in tufa-associated biofilms of two
      German hard-water creeks by employing fluorescence lectin-binding analysis
      (FLBA), (ii) to verify the specific lectin-binding pattern by competitive
      inhibition assays, and (iii) to assess whether carbonates are associated with
      structural EPS domains. Three major in situ EPS domains (cyanobacterial, network
      like, and cloud-like structures) were detected by FLBA in combination with laser
      scanning microscopy (LSM). Based on lectin specificity, the EPS glycoconjugates
      produced by cyanobacteria contained mainly fucose, amino sugars (N-acetyl
      glucosamine and N-acetyl-galactosamine), and sialic acid. Tufa deposits were
      irregularly covered by network-like EPS structures, which may originate from
      cyanobacterial EPS secretions. Cloud-like EPS glycoconjugates were dominated by
      sialic acid, amino sugars, and galactose. In some cases calcium carbonate
      crystals were associated with cyanobacterial EPS glycoconjugates. The detection
      of amino sugars and calcium carbonate in close association with decaying sheath
      material indicated that microbially mediated processes might be important for
      calcium carbonate precipitation in freshwater tufa systems.

PMID- 21097579
TI  - Characterization of three lactic acid bacteria and their isogenic ldh deletion
      mutants shows optimization for YATP (cell mass produced per mole of ATP) at their
      physiological pHs.
AB  - Several lactic acid bacteria use homolactic acid fermentation for generation of
      ATP. Here we studied the role of the lactate dehydrogenase enzyme on the general
      physiology of the three homolactic acid bacteria Lactococcus lactis, Enterococcus
      faecalis, and Streptococcus pyogenes. Of note, deletion of the ldh genes hardly
      affected the growth rate in chemically defined medium under microaerophilic
      conditions. However, the growth rate was affected in rich medium. Furthermore,
      deletion of ldh affected the ability for utilization of various substrates as a
      carbon source. A switch to mixed acid fermentation was observed during glucose
      limited continuous growth and was dependent on the growth rate for S. pyogenes
      and on the pH for E. faecalis. In S. pyogenes and L. lactis, a change in pH
      resulted in a clear change in Y(ATP) (cell mass produced per mole of ATP). The pH
      that showed the highest Y(ATP) corresponded to the pH of the natural habitat of
      the organisms.

PMID- 21097580
TI  - Characterization of lytic enzyme open reading frame 9 (ORF9) derived from
      Enterococcus faecalis bacteriophage phiEF24C.
AB  - In bacteriophage (phage) therapy against Gram-positive bacteria, such as
      Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis, members
      of a genus of SPO1-like viruses are typically employed because of their extreme
      virulence and broad host spectrum. Phage phiEF24C, which is a SPO1-like virus
      infecting E. faecalis, has previously been characterized as a therapeutic phage
      candidate. In addition to the phage itself, phage endolysin is also recognized as
      an effective antimicrobial agent. In this study, a putative endolysin gene (orf9)
      of E. faecalis phage phiEF24C was analyzed in silico, and its activity was
      characterized using the recombinant form. First, bioinformatics analysis
      predicted that the open reading frame 9 (ORF9) protein is N-acetylmuramoyl-l
      alanine amidase. Second, bacteriolytic and bactericidal activities of ORF9
      against E. faecalis were confirmed by zymography, decrease of peptidoglycan
      turbidity, decrease of the viable count, and morphological analysis of ORF9
      treated cells. Third, ORF9 did not appear to require Zn(2+) ions for its
      activity, contrary to the bioinformatics prediction of a Zn(2+) ion requirement.
      Fourth, the lytic spectrum was from 97.1% (34 out of 35 strains, including
      vancomycin-resistant strains) of E. faecalis strains to 60% (6 out of 10 strains)
      of Enterococcus faecium strains. Fifth, N-acetylmuramoyl-l-alanine amidase
      activity of ORF9 was confirmed by matrix-assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS) and the subsequent MALDI
      postsource decay (PSD) analyses. Finally, functional analysis using N- or C
      terminally deleted ORF9 mutants suggested that a complete ORF9 molecule is
      essential for its activity. These results suggested that ORF9 is an endolysin of
      phage phiEF24C and can be a therapeutic alternative to antibiotics.

PMID- 21097581
TI  - Polyphyletic origin of Vibrio vulnificus biotype 2 as revealed by sequence-based
      analysis.
AB  - A sequence-based analysis of seven housekeeping and virulence-related genes shows
      that the species Vibrio vulnificus is subdivided into three phylogenetic lineages
      that do not correspond with the biotypes and that biotype 2 is polyphyletic.
      These results support the reclassification of biotype 2 as a pathovar that would
      group the strains with pathogenic potential to develop vibriosis in fish.

PMID- 21097582
TI  - Application of a depositional facies model to an acid mine drainage site.
AB  - Lower Red Eyes is an acid mine drainage site in Pennsylvania where low-pH Fe(II)
      oxidation has created a large, terraced iron mound downstream of an anoxic,
      acidic, metal-rich spring. Aqueous chemistry, mineral precipitates, microbial
      communities, and laboratory-based Fe(II) oxidation rates for this site were
      analyzed in the context of a depositional facies model. Depositional facies were
      defined as pools, terraces, or microterracettes based on cm-scale sediment
      morphology, irrespective of the distance downstream from the spring. The
      sediments were composed entirely of Fe precipitates and cemented organic matter.
      The Fe precipitates were identified as schwertmannite at all locations,
      regardless of facies. Microbial composition was studied with fluorescence in situ
      hybridization (FISH) and transitioned from a microaerophilic, Euglena-dominated
      community at the spring, to a Betaproteobacteria (primarily Ferrovum spp.)
      dominated community at the upstream end of the iron mound, to a
      Gammaproteobacteria (primarily Acidithiobacillus)-dominated community at the
      downstream end of the iron mound. Microbial community structure was more strongly
      correlated with pH and geochemical conditions than depositional facies. Intact
      pieces of terrace and pool sediments from upstream and downstream locations were
      used in flowthrough laboratory reactors to measure the rate and extent of low-pH
      Fe(II) oxidation. No change in Fe(II) concentration was observed with (60)Co
      irradiated sediments or with no-sediment controls, indicating that abiotic Fe(II)
      oxidation was negligible. Upstream sediments attained lower effluent Fe(II)
      concentrations compared to downstream sediments, regardless of depositional
      facies.

PMID- 21097583
TI  - Changes in dimethylsulfoniopropionate demethylase gene assemblages in response to
      an induced phytoplankton bloom.
AB  - Over half of the bacterioplankton cells in ocean surface waters are capable of
      carrying out a demethylation of the phytoplankton metabolite
      dimethylsulfoniopropionate (DMSP) that routes the sulfur moiety away from the
      climatically active gas dimethylsulfide (DMS). In this study, we tracked changes
      in dmdA, the gene responsible for DMSP demethylation, over the course of an
      induced phytoplankton bloom in Gulf of Mexico seawater microcosms. Analysis of
      >91,000 amplicon sequences indicated 578 different dmdA sequence clusters at a
      conservative clustering criterion of >=90% nucleotide sequence identity over the
      6-day study. The representation of the major clades of dmdA, several of which are
      linked to specific taxa through genomes of cultured marine bacterioplankton,
      remained fairly constant. However, the representation of clusters within these
      major clades shifted significantly in response to the bloom, including two
      Roseobacter-like clusters and a SAR11-like cluster, and the best correlate with
      shifts of the dominant dmdA clades was chlorophyll a concentration. Concurrent
      16S rRNA amplification and sequencing indicated the presence of Roseobacter,
      SAR11, OM60, and marine Rhodospirillales populations, all of which are known to
      harbor dmdA genes, although the largest taxonomic change was an increase in
      Flavobacteriaceae, a group not yet demonstrated to have DMSP-demethylating
      capabilities. Sequence heterogeneity in dmdA and other functional gene
      populations is becoming increasingly evident with the advent of high-throughput
      sequencing technologies, and understanding the ecological implications of this
      heterogeneity is a major challenge for marine microbial ecology.

PMID- 21097585
TI  - Genomic and functional analyses of Rhodococcus equi phages ReqiPepy6, ReqiPoco6,
      ReqiPine5, and ReqiDocB7.
AB  - The isolation and results of genomic and functional analyses of Rhodococcus equi
      phages ReqiPepy6, ReqiDocB7, ReqiPine5, and ReqiPoco6 (hereafter referred to as
      Pepy6, DocB7, Pine5, and Poco6, respectively) are reported. Two phages, Pepy6 and
      Poco6, more than 75% identical, exhibited genome organization and protein
      sequence likeness to Lactococcus lactis phage 1706 and clostridial prophage
      elements. An unusually high fraction, 27%, of Pepy6 and Poco6 proteins were
      predicted to possess at least one transmembrane domain, a value much higher than
      the average of 8.5% transmembrane domain-containing proteins determined from a
      data set of 36,324 phage protein entries. Genome organization and protein
      sequence comparisons place phage Pine5 as the first nonmycobacteriophage member
      of the large Rosebush cluster. DocB7, which had the broadest host range among the
      four isolates, was not closely related to any phage or prophage in the database,
      and only 23 of 105 predicted encoded proteins could be assigned a functional
      annotation. Because of the relationship of Rhodococcus to Mycobacterium, it was
      anticipated that these phages should exhibit some of the features characteristic
      of mycobacteriophages. Traits that were identified as shared by the Rhodococcus
      phages and mycobacteriophages include the prevalent long-tailed morphology and
      the presence of genes encoding LysB-like mycolate-hydrolyzing lysis proteins.
      Application of DocB7 lysates to soils amended with a host strain of R. equi
      reduced recoverable bacterial CFU, suggesting that phage may be useful in
      limiting R. equi load in the environment while foals are susceptible to
      infection.

PMID- 21097584
TI  - Cultivation-independent analysis of bacteria in IDEXX Quanti-Tray/2000 fecal
      indicator assays.
AB  - Monitoring microbiological water quality is important for protecting water
      resources and the health of swimmers. Routine monitoring relies on cultivating
      fecal indicator bacteria (FIB), frequently using defined substrate technology.
      Defined substrate technology is designed to specifically enrich for FIB, but a
      complete understanding of the assay microbiology requires culture-independent
      analysis of the enrichments. This study aimed to identify bacteria in positive
      wells of Colilert and Enterolert Quanti-Tray/2000 (IDEXX Laboratories) FIB assays
      in environmental water samples and to quantify the degree of false-positive
      results for samples from an urban creek by molecular methods. Pooled Escherichia
      coli- and Enterococcus-positive Quanti-Tray/2000 enrichments, either from urban
      creek dry weather flow or municipal sewage, harbored diverse bacterial
      populations based on 16S rRNA gene sequences and terminal restriction fragment
      length polymorphism analyses. Target taxa (coliforms or enterococci) and
      nontarget taxa (Vibrio spp., Shewanella spp., Bacteroidetes, and Clostridium
      spp.) were identified in pooled and individual positive Colilert and Enterolert
      wells based on terminal restriction fragments that were in common with those
      generated in silico from clone sequences. False-positive rates of between 4 and
      23% occurred for the urban creek samples, based on the absence of target terminal
      restriction fragments in individual positive wells. This study suggests that
      increased selective inhibition of nontarget bacteria could improve the accuracy
      of the Colilert and Enterolert assays.

PMID- 21097587
TI  - Methicillin-resistant Staphylococcus aureus in pork production shower facilities.
AB  - As methicillin-resistant Staphylococcus aureus (MRSA) has been found in pigs, we
      sought to determine if MRSA is present in pork production shower facilities. In
      two production systems tested, 3% and 26% of shower samples were positive for
      MRSA. spa types identified included t034, t189, t753, and t1746.

PMID- 21097586
TI  - Concentration and diversity of uncultured Legionella spp. in two unchlorinated
      drinking water supplies with different concentrations of natural organic matter.
AB  - Two unchlorinated drinking water supplies were investigated to assess the
      potential of water treatment and distribution systems to support the growth of
      Legionella spp. The treatment plant for supply A distributed treated groundwater
      with a low concentration (<0.5 ppm of C) of natural organic matter (NOM), and the
      treatment plant for supply B distributed treated groundwater with a high NOM
      concentration (8 ppm of C). In both supplies, the water temperature ranged from
      about 10 degrees C after treatment to 18 degrees C during distribution. The
      concentrations of Legionella spp. in distributed water, analyzed with
      quantitative PCR (Q-PCR), averaged 2.9 (+/- 1.9) * 10(2) cells liter(-1) in
      supply A and 2.5 (+/- 1.6) * 10(3) cells liter(-1) in supply B. No Legionella was
      observed with the culture method. A total of 346 clones (96 operational
      taxonomical units [OTUs] with >=97% sequence similarity) were retrieved from
      water and biofilms of supply A and 251 (43 OTUs) from supply B. The estimation of
      the average value of total species richness (Chao1) in supply A (153) was clearly
      higher than that for supply B (58). In each supply, about 77% of the sequences
      showed <97% similarity to described species. Sequences related to L. pneumophila
      were only incidentally observed. The Legionella populations of the two supplies
      are divided into two distinct clusters based on distances in the phylogenetic
      tree as fractions of the branch length. Thus, a large variety of mostly yet
      undescribed Legionella spp. proliferates in unchlorinated water supplies at
      temperatures below 18 degrees C. The lowest concentration and greatest diversity
      were observed in the supply with the low NOM concentration.

PMID- 21097588
TI  - L-malate production by metabolically engineered Escherichia coli.
AB  - Escherichia coli strains (KJ060 and KJ073) that were previously developed for
      succinate production have now been modified for malate production. Many
      unexpected changes were observed during this investigation. The initial strategy
      of deleting fumarase isoenzymes was ineffective, and succinate continued to
      accumulate. Surprisingly, a mutation in fumarate reductase alone was sufficient
      to redirect carbon flow into malate even in the presence of fumarase. Further
      deletions were needed to inactivate malic enzymes (typically gluconeogenic) and
      prevent conversion to pyruvate. However, deletion of these genes (sfcA and maeB)
      resulted in the unexpected accumulation of D-lactate despite the prior deletion
      of mgsA and ldhA and the absence of apparent lactate dehydrogenase activity.
      Although the metabolic source of this D-lactate was not identified, lactate
      accumulation was increased by supplementation with pyruvate and decreased by the
      deletion of either pyruvate kinase gene (pykA or pykF) to reduce the supply of
      pyruvate. Many of the gene deletions adversely affected growth and cell yield in
      minimal medium under anaerobic conditions, and volumetric rates of malate
      production remained low. The final strain (XZ658) produced 163 mM malate, with a
      yield of 1.0 mol (mol glucose(-1)), half of the theoretical maximum. Using a two
      stage process (aerobic cell growth and anaerobic malate production), this
      engineered strain produced 253 mM malate (34 g liter(-1)) within 72 h, with a
      higher yield (1.42 mol mol(-1)) and productivity (0.47 g liter(-1) h(-1)). This
      malate yield and productivity are equal to or better than those of other known
      biocatalysts.

PMID- 21097589
TI  - Metatranscriptome analysis for insight into whole-ecosystem gene expression
      during spontaneous wheat and spelt sourdough fermentations.
AB  - Lactic acid bacteria (LAB) are of industrial importance in the production of
      fermented foods, including sourdough-derived products. Despite their limited
      metabolic capacity, LAB contribute considerably to important characteristics of
      fermented foods, such as extended shelf-life, microbial safety, improved texture,
      and enhanced organoleptic properties. Triggered by the considerable amount of LAB
      genomic information that became available during the last decade, transcriptome
      and, by extension, metatranscriptome studies have become one of the most
      appropriate research approaches to study whole-ecosystem gene expression in more
      detail. In this study, microarray analyses were performed using RNA sampled
      during four 10-day spontaneous sourdough fermentations carried out in the
      laboratory with an in-house-developed LAB functional gene microarray. For data
      analysis, a new algorithm was developed to calculate a net expression profile for
      each of the represented genes, allowing use of the microarray analysis beyond the
      species level. In addition, metabolite target analyses were performed on the
      sourdough samples to relate gene expression with metabolite production. The
      results revealed the activation of different key metabolic pathways, the ability
      to use carbohydrates other than glucose (e.g., starch and maltose), and the
      conversion of amino acids as a contribution to redox equilibrium and flavor
      compound generation in LAB during sourdough fermentation.

PMID- 21097590
TI  - Integron prevalence and diversity in manured soil.
AB  - The levels of integron abundance and diversity in soil amended with pig slurry
      were studied. Real-time PCR illustrated a significant increase in class 1
      integron prevalence after slurry application, with increased prevalence still
      evident at 10 months after application. Culture-dependent data revealed 10
      genera, including putative human pathogens, carrying class 1 and 2 integrons.

PMID- 21097592
TI  - Prevalence of Helicobacter pullorum in conventional, organic, and free-range
      broilers and typing of isolates.
AB  - Helicobacter pullorum represents a potential food-borne pathogen, and avian
      species appear to be a relevant reservoir of this organism. In this study, the
      prevalence of H. pullorum was investigated at 30 conventional farms where 169
      ceca from 34 flocks were tested, at eight organic farms where 39 ceca from eight
      flocks were tested, and at seven free-range farms where 40 ceca from eight flocks
      were tested. All of the ceca were obtained from healthy broiler chickens.
      Moreover, amplified fragment length polymorphism, pulsed-field gel
      electrophoresis, and automated ribotyping were employed to estimate the levels of
      genetic variability of H. pullorum broiler isolates within and between flocks.
      Overall, Gram-negative, slender, curved rods, identified as H. pullorum by PCR,
      were isolated at 93.3% of the farms tested. The percentage of positive free-range
      farms (54.2%) was significantly lower than that of conventional (100%) or organic
      (100%) farms (P < 0.001). The level of within-flock genetic variability,
      calculated as the number of flocks colonized by isolates genetically different by
      all of the typing methods, was 34.9%. Isolates showing identical profiles by each
      typing method were observed in 11.6% of the flocks, but they were never detected
      between flocks. However, groups of isolates clustered together with an overall
      similarity level of >=85%. Our results suggest that even though a high level of
      genetic variability is attributable to H. pullorum broiler isolates, their
      hierarchical genotyping produces data useful for epidemiological investigations.

PMID- 21097591
TI  - Diversity of the fsr-gelE region of the Enterococcus faecalis genome but
      conservation in strains with partial deletions of the fsr operon.
AB  - Most Enterococcus faecalis isolates carry gelE, but many are gelatinase
      nonproducers due to the lack of fsrC (EF_1820) to EF_1841 (fsrC-EF_1841; 23.9 kb
      in strain V583), including most of the locus encoding Fsr, which activates gelE
      expression. Analysis of 22 accessible E. faecalis genomes revealed the identity
      of the 53-amino-acid propeptide of fsrD across multiple MLSTs (multilocus
      sequence types), although 12 distinctly different variations were found in the
      EF_1814-to-EF_1902 region. Diversity was seen in fsrABC, in the region EF_1814 to
      EF_1902, and in a 700-kb region surrounding fsrC-EF_1841. However, analysis of
      five sequenced strains carrying the fsrC-EF_1841 deletion and the putative
      integrative conjugative element efaB5 showed almost identical single nucleotide
      polymorphisms (SNPs) in gelE and an identical junction sequence, despite their
      unrelated MLSTs, in contrast to those shown by strains without the deletion.
      Further analysis confirmed the conserved gelE SNPs in 6 additional strains (11 in
      total) with the deletion. While we were unable to detect evidence of spontaneous
      deletion using OG1RF and 8 other strains, we were able to engineer a deletion of
      the 37-kb fsrC-EF_1841 region of OG1RF without deleterious effects, and the 37-kb
      mutant showed changes in biofilm and chaining similar to those shown by fsr-gelE
      mutants. In conclusion, we describe the identity of fsrD despite high plasticity
      within the fsrC-EF_1841 region and the surrounding sequence. However, strains
      lacking the fsrC-EF_1841 region show a distinct conservation of the sequence
      surrounding this deletion and in gelE, suggesting that the deletion may result
      from horizontal transfer and recombination.

PMID- 21097593
TI  - Anaerobic obligatory xylitol production in Escherichia coli strains devoid of
      native fermentation pathways.
AB  - Anaerobic glucose oxidation was coupled to xylose reduction in a nonfermentative
      Escherichia coli strain expressing NADPH-dependent xylose reductase. Xylitol
      production serves as the primary means of NAD(P)(+) regeneration, as glucose is
      converted primarily to acetate and CO(2). The membrane-bound transhydrogenase
      PntAB is required to achieve the maximum theoretical yield of four moles of
      xylitol per mole of glucose consumed.

PMID- 21097595
TI  - Utilization of natural fucosylated oligosaccharides by three novel alpha-L
      fucosidases from a probiotic Lactobacillus casei strain.
AB  - Three putative alpha-L-fucosidases encoded in the Lactobacillus casei BL23 genome
      were cloned and purified. The proteins displayed different abilities to hydrolyze
      natural fucosyloligosaccharides like 2'-fucosyllactose, H antigen disaccharide, H
      antigen type II trisaccharide, and 3'-, 4'-, and 6'-fucosyl-GlcNAc. This
      indicated a possible role in the utilization of oligosaccharides present in human
      milk and intestinal mucosa.

PMID- 21097596
TI  - Requirements of the engineered leader peptide of nisin for inducing modification,
      export, and cleavage.
AB  - Nisin A is a pentacyclic peptide antibiotic produced by Lactococcus lactis. The
      leader peptide of prenisin keeps nisin inactive and has a role in inducing NisB-
      and NisC-catalyzed modifications of the propeptide and NisT-mediated export. The
      highly specific NisP cleaves off the leader peptide from fully modified and
      exported prenisin. We present here a detailed mutagenesis analysis of the nisin
      leader peptide. For alternative cleavage, we successfully introduced a putative
      NisP autocleavage site and sites for thrombin, enterokinase, Glu-C, and factor Xa
      in the C-terminal part of the leader peptide. Replacing residue F-18 with Trp or
      Thr strongly reduced production. On the other hand, D-19A, F-18H, F-18M, L-16D, L
      16K, and L-16A enhanced production. Substitutions within and outside the FNLD box
      enhanced or reduced the transport efficiency. None of the above substitutions nor
      even an internal 6His tag from positions -13 to -8 had any effect on the capacity
      of the leader peptide to induce NisB and NisC modifications. Therefore, these
      data demonstrate a large mutational freedom. However, simultaneous replacement of
      the FNLD amino acids by four alanines strongly reduced export and even led to a
      complete loss of the capacity to induce modifications. Reducing the leader
      peptide to MSTKDFNLDLR led to 3- or 4-fold dehydration. Taken together, the FNLD
      box is crucial for inducing posttranslational modifications.

PMID- 21097597
TI  - Mycolic acid-containing bacteria induce natural-product biosynthesis in
      Streptomyces species.
AB  - Natural products produced by microorganisms are important starting compounds for
      drug discovery. Secondary metabolites, including antibiotics, have been isolated
      from different Streptomyces species. The production of these metabolites depends
      on the culture conditions. Therefore, the development of a new culture method can
      facilitate the discovery of new natural products. Here, we show that mycolic acid
      containing bacteria can influence the biosynthesis of cryptic natural products in
      Streptomyces species. The production of red pigment by Streptomyces lividans TK23
      was induced by coculture with Tsukamurella pulmonis TP-B0596, which is a mycolic
      acid-containing bacterium. Only living cells induced this pigment production,
      which was not mediated by any substances. T. pulmonis could induce natural
      product synthesis in other Streptomyces strains too: it altered natural-product
      biosynthesis in 88.4% of the Streptomyces strains isolated from soil. The other
      mycolic acid-containing bacteria, Rhodococcus erythropolis and Corynebacterium
      glutamicum, altered biosynthesis in 87.5 and 90.2% of the Streptomyces strains,
      respectively. The coculture broth of T. pulmonis and Streptomyces endus S-522
      contained a novel antibiotic, which we named alchivemycin A. We concluded that
      the mycolic acid localized in the outer cell layer of the inducer bacterium
      influences secondary metabolism in Streptomyces, and this activity is a result of
      the direct interaction between the mycolic acid-containing bacteria and
      Streptomyces. We used these results to develop a new coculture method, called the
      combined-culture method, which facilitates the screening of natural products.

PMID- 21097598
TI  - The type II secretion system is essential for erythrocyte lysis and gut
      colonization by the leech digestive tract symbiont Aeromonas veronii.
AB  - Hemolysin and the type II secretion system (T2SS) have been shown to be important
      for virulence in many pathogens, but very few studies have shown their importance
      in beneficial microbes. Here, we investigated the importance of the type II
      secretion pathway in the beneficial digestive-tract association of Aeromonas
      veronii and the medicinal leech Hirudo verbana and revealed a critical role for
      the hemolysis of erythrocytes. A mutant with a miniTn5 insertion in exeM, which
      is involved in forming the inner membrane platform in the T2SS, was isolated by
      screening mutants for loss of hemolysis on blood agar plates. A hemolysis assay
      was used to quantify the mutant's deficiency in lysing sheep erythrocytes and
      revealed a 99.9% decrease compared to the parent strain. The importance of the
      T2SS in the colonization of the symbiotic host was assessed. Colonization assays
      revealed that the T2SS is critical for initial colonization of the leech gut. The
      defect was tied to the loss of hemolysin production by performing a colonization
      assay with blood containing lysed erythrocytes. This restored the colonization
      defect in the mutant. Complementation of the mutant using the promoter region and
      exeMN revealed that the T2SS is responsible for secreting hemolysin into the
      extracellular space and that both the T2SS and hemolysin export by the T2SS are
      critical for initial establishment of A. veronii in the leech gut.

PMID- 21097599
TI  - Complete biodegradation of 4-fluorocinnamic acid by a consortium comprising
      Arthrobacter sp. strain G1 and Ralstonia sp. strain H1.
AB  - A consortium of the newly isolated bacterial strains Arthrobacter sp. strain G1
      and Ralstonia sp. strain H1 utilized 4-fluorocinnamic acid for growth under
      aerobic conditions. Strain G1 converted 4-fluorocinnamic acid into 4
      fluorobenzoic acid and used the two-carbon side chain for growth, with some
      formation of 4-fluoroacetophenone as a dead-end side product. In the presence of
      strain H1, complete mineralization of 4-fluorocinnamic acid and release of
      fluoride were obtained. Degradation of 4-fluorocinnamic acid by strain G1
      occurred through a beta-oxidation mechanism and started with the formation of 4
      fluorocinnamoyl-coenzyme A (CoA), as indicated by the presence of 4
      fluorocinnamoyl-CoA ligase. Enzymes for further transformation were detected in
      cell extract, i.e., 4-fluorocinnamoyl-CoA hydratase, 4-fluorophenyl-beta-hydroxy
      propionyl-CoA dehydrogenase, and 4-fluorophenyl-beta-keto propionyl-CoA thiolase.
      Degradation of 4-fluorobenzoic acid by strain H1 proceeded via 4-fluorocatechol,
      which was converted by an ortho-cleavage pathway.

PMID- 21097594
TI  - Influence of plant polymers on the distribution and cultivation of bacteria in
      the phylum Acidobacteria.
AB  - Members of the phylum Acidobacteria are among the most abundant bacteria in soil.
      Although they have been characterized as versatile heterotrophs, it is unclear if
      the types and availability of organic resources influence their distribution in
      soil. The potential for organic resources to select for different acidobacteria
      was assessed using molecular and cultivation-based approaches with agricultural
      and managed grassland soils in Michigan. The distribution of acidobacteria varied
      with the carbon content of soil: the proportion of subdivision 4 sequences was
      highest in agricultural soils (ca. 41%) that contained less carbon than grassland
      soils, where the proportions of subdivision 1, 3, 4, and 6 sequences were
      similar. Either readily oxidizable carbon or plant polymers were used as the sole
      carbon and energy source to isolate heterotrophic bacteria from these soils.
      Plant polymers increased the diversity of acidobacteria cultivated but decreased
      the total number of heterotrophs recovered compared to readily oxidizable carbon.
      Two phylogenetically novel Acidobacteria strains isolated on the plant polymer
      medium were characterized. Strains KBS 83 (subdivision 1) and KBS 96 (subdivision
      3) are moderate acidophiles with pH optima of 5.0 and 6.0, respectively. Both
      strains grew slowly (MU = 0.01 h(-1)) and harbored either 1 (strain KBS 83) or 2
      (strain KBS 96) copies of the 16S rRNA encoding gene-a genomic characteristic
      typical of oligotrophs. Strain KBS 83 is a microaerophile, growing optimally at
      8% oxygen. These metabolic characteristics help delineate the niches that
      acidobacteria occupy in soil and are consistent with their widespread
      distribution and abundance.

PMID- 21097600
TI  - Mechanisms of contact-mediated killing of yeast cells on dry metallic copper
      surfaces.
AB  - Surfaces made of copper or its alloys have strong antimicrobial properties
      against a wide variety of microorganisms. However, the molecular mode of action
      responsible for the antimicrobial efficacy of metallic copper is not known. Here,
      we show that dry copper surfaces inactivate Candida albicans and Saccharomyces
      cerevisiae within minutes in a process called contact-mediated killing. Cellular
      copper ion homeostasis systems influenced the kinetics of contact-mediated
      killing in both organisms. Deregulated copper ion uptake through a hyperactive S.
      cerevisiae Ctr1p (ScCtr1p) copper uptake transporter in Saccharomyces resulted in
      faster inactivation of mutant cells than of wild-type cells. Similarly, lack of
      the C. albicans Crp1p (CaCrp1p) copper-efflux P-type ATPase or the
      metallothionein CaCup1p caused more-rapid killing of Candida mutant cells than of
      wild-type cells. Candida and Saccharomyces took up large quantities of copper
      ions as soon as they were in contact with copper surfaces, as indicated by
      inductively coupled plasma mass spectroscopy (ICP-MS) analysis and by the
      intracellular copper ion-reporting dye coppersensor-1. Exposure to metallic
      copper did not cause lethality through genotoxicity, deleterious action on a
      cell's genetic material, as indicated by a mutation assay with Saccharomyces.
      Instead, toxicity mediated by metallic copper surfaces targeted membranes in both
      yeast species. With the use of Live/Dead staining, onset of rapid and extensive
      cytoplasmic membrane damage was observed in cells from copper surfaces.
      Fluorescence microscopy using the indicator dye DiSBaC(2)(3) indicated that cell
      membranes were depolarized. Also, during contact-mediated killing, vacuoles first
      became enlarged and then disappeared from the cells. Lastly, in metallic copper
      stressed yeasts, oxidative stress in the cytoplasm and in mitochondria was
      elevated.

PMID- 21097601
TI  - Role of tyramine synthesis by food-borne Enterococcus durans in adaptation to the
      gastrointestinal tract environment.
AB  - Biogenic amines in food constitute a human health risk. Here we report that
      tyramine-producing Enterococcus durans strain IPLA655 (from cheese) was able to
      produce tyramine under conditions simulating transit through the gastrointestinal
      tract. Activation of the tyramine biosynthetic pathway contributed to binding and
      immunomodulation of enterocytes.

PMID- 21097603
TI  - Construction and characterization of a lactose-inducible promoter system for
      controlled gene expression in Clostridium perfringens.
AB  - Clostridium perfringens is a Gram-positive anaerobic pathogen which causes many
      diseases in humans and animals. While some genetic tools exist for working with
      C. perfringens, a tightly regulated, inducible promoter system is currently
      lacking. Therefore, we constructed a plasmid-based promoter system that provided
      regulated expression when lactose was added. This plasmid (pKRAH1) is an
      Escherichia coli-C. perfringens shuttle vector containing the gene encoding a
      transcriptional regulator, BgaR, and a divergent promoter upstream of gene bgaL
      (bgaR-P(bgaL)). To measure transcription at the bgaL promoter in pKRAH1, the E.
      coli reporter gene gusA, encoding beta-glucuronidase, was placed downstream of
      the P(bgaL) promoter to make plasmid pAH2. When transformed into three strains of
      C. perfringens, pAH2 exhibited lactose-inducible expression. C. perfringens
      strain 13, a commonly studied strain, has endogenous beta-glucuronidase activity.
      We mutated gene bglR, encoding a putative beta-glucuronidase, and observed an 89%
      decrease in endogenous activity with no lactose. This combination of a system for
      regulated gene expression and a mutant of strain 13 with low beta-glucuronidase
      activity are useful tools for studying gene regulation and protein expression in
      an important pathogenic bacterium. We used this system to express the yfp-pilB
      gene, comprised of a yellow fluorescent protein (YFP)-encoding gene fused to an
      assembly ATPase gene involved in type IV pilus-dependent gliding motility in C.
      perfringens. Expression in the wild-type strain showed that YFP-PilB localized
      mostly to the poles of cells, but in a pilC mutant it localized throughout the
      cell, demonstrating that the membrane protein PilC is required for polar
      localization of PilB.

PMID- 21097602
TI  - GeoChip-based analysis of the functional gene diversity and metabolic potential
      of microbial communities in acid mine drainage.
AB  - Acid mine drainage (AMD) is an extreme environment, usually with low pH and high
      concentrations of metals. Although the phylogenetic diversity of AMD microbial
      communities has been examined extensively, little is known about their functional
      gene diversity and metabolic potential. In this study, a comprehensive functional
      gene array (GeoChip 2.0) was used to analyze the functional diversity,
      composition, structure, and metabolic potential of AMD microbial communities from
      three copper mines in China. GeoChip data indicated that these microbial
      communities were functionally diverse as measured by the number of genes
      detected, gene overlapping, unique genes, and various diversity indices. Almost
      all key functional gene categories targeted by GeoChip 2.0 were detected in the
      AMD microbial communities, including carbon fixation, carbon degradation, methane
      generation, nitrogen fixation, nitrification, denitrification, ammonification,
      nitrogen reduction, sulfur metabolism, metal resistance, and organic contaminant
      degradation, which suggested that the functional gene diversity was higher than
      was previously thought. Mantel test results indicated that AMD microbial
      communities are shaped largely by surrounding environmental factors (e.g., S, Mg,
      and Cu). Functional genes (e.g., narG and norB) and several key functional
      processes (e.g., methane generation, ammonification, denitrification, sulfite
      reduction, and organic contaminant degradation) were significantly (P < 0.10)
      correlated with environmental variables. This study presents an overview of
      functional gene diversity and the structure of AMD microbial communities and also
      provides insights into our understanding of metabolic potential in AMD
      ecosystems.

PMID- 21097604
TI  - Chronic electrical stimulation of the carotid sinus baroreflex improves left
      ventricular function and promotes reversal of ventricular remodeling in dogs with
      advanced heart failure.
AB  - BACKGROUND: Autonomic abnormalities exist in heart failure and contribute to
      disease progression. Activation of the carotid sinus baroreflex (CSB) has been
      shown to reduce sympathetic outflow and augment parasympathetic vagal tone. This
      study tested the hypothesis that long-term electric activation of the CSB
      improves left ventricular (LV) function and attenuates progressive LV remodeling
      in dogs with advanced chronic heart failure. METHODS AND RESULTS: Studies were
      performed in 14 dogs with coronary microembolization-induced heart failure (LV
      ejection fraction ~25%). Eight dogs were chronically instrumented for bilateral
      CSB activation using the Rheos System (CVRx Inc, Minneapolis, Minn) and 6 were
      not and served as controls. All dogs were followed for 3 months, and none
      received other background therapy. During follow-up, treatment with CSB increased
      LV ejection fraction 4.0+/-2.4% compared with a reduction in control dogs of 
      2.8+/-1.0% (P<0.05). Similarly, treatment with CSB decreased LV end-systolic
      volume -2.5+/-2.7 mL compared with an increase in control dogs of 6.7+/-2.9 mL
      (P<0.05). Compared with control, CSB activation significantly decreased LV end
      diastolic pressure and circulating plasma norepinephrine, normalized expression
      of cardiac beta(1)-adrenergic receptors, beta-adrenergic receptor kinase, and
      nitric oxide synthase and reduced interstitial fibrosis and cardiomyocyte
      hypertrophy. CONCLUSIONS: In dogs with advanced heart failure, CSB activation
      improves global LV function and partially reverses LV remodeling both globally
      and at cellular and molecular levels.

PMID- 21097605
TI  - Myocardial parvovirus B19 persistence: lack of association with clinicopathologic
      phenotype in adults with heart failure.
AB  - BACKGROUND: Multiple viruses have been isolated from the heart, but their
      significance remains controversial. We sought to determine the prevalence of
      cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult patients
      with heart failure (HF) and to define the clinicopathologic profile of patients
      exhibiting viral positivity. METHODS AND RESULTS: EMB from 100 patients (median
      ejection fraction, 30%; interquartile range [IQR], 20% to 45%) presenting for
      cardiomyopathy evaluation (median symptom duration, 5 months; IQR, 1 to 13
      months) were analyzed by polymerase chain reaction for adenovirus,
      cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each
      isolate was sequenced, and viral load was determined. Parvovirus B19 was the only
      virus detected in EMB samples (12% of subjects). No patient had antiparvovirus
      IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The
      clinical presentation of parvovirus-positive patients was markedly heterogeneous
      with both acute and chronic HF, variable ventricular function, and ischemic
      cardiomyopathy. No patient met Dallas histopathologic criteria for active or
      borderline myocarditis. Two patients with a positive cardiac MRI and presumed
      "parvomyocarditis" had similar viral loads to autopsy controls without heart
      disease. The oldest parvovirus-positive patients were positive for genotype 2,
      suggesting lifelong persistence in the myocardium. CONCLUSIONS: Parvovirus B19
      was the only virus isolated from EMB samples in this series of adult patients
      with HF from the United States. Positivity was associated with a wide array of
      clinical presentations and HF phenotypes. Our studies do not support a causative
      role for parvovirus B19 persistence in HF and, therefore, advocate against the
      use of antiviral therapy for these patients.

PMID- 21097606
TI  - 'Silent' priming of translation-dependent LTP by beta-adrenergic receptors
      involves phosphorylation and recruitment of AMPA receptors.
AB  - The capacity for long-term changes in synaptic efficacy can be altered by prior
      synaptic activity, a process known as "metaplasticity." Activation of receptors
      for modulatory neurotransmitters can trigger downstream signaling cascades that
      persist beyond initial receptor activation and may thus have metaplastic effects.
      Because activation of beta-adrenergic receptors (beta-ARs) strongly enhances the
      induction of long-term potentiation (LTP) in the hippocampal CA1 region, we
      examined whether activation of these receptors also had metaplastic effects on
      LTP induction. Our results show that activation of beta-ARs induces a protein
      synthesis-dependent form of metaplasticity that primes the future induction of
      late-phase LTP by a subthreshold stimulus. beta-AR activation also induced a long
      lasting increase in phosphorylation of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor (AMPAR) GluA1 subunits at a protein kinase A
      (PKA) site (S845) and transiently activated extracellular signal-regulated kinase
      (ERK). Consistent with this, inhibitors of PKA and ERK blocked the metaplastic
      effects of beta-AR activation. beta-AR activation also induced a prolonged,
      translation-dependent increase in cell surface levels of GluA1 subunit-containing
      AMPA receptors. Our results indicate that beta-ARs can modulate hippocampal
      synaptic plasticity by priming synapses for the future induction of late-phase
      LTP through up-regulation of translational processes, one consequence of which is
      the trafficking of AMPARs to the cell surface.

PMID- 21097607
TI  - Long-term maintenance of immediate or delayed extinction is determined by the
      extinction-test interval.
AB  - Short acquisition-extinction intervals (immediate extinction) can lead to either
      more or less spontaneous recovery than long acquisition-extinction intervals
      (delayed extinction). Using rat subjects, we observed less spontaneous recovery
      following immediate than delayed extinction (Experiment 1). However, this was the
      case only if a relatively long extinction-test interval was used; a relatively
      short extinction-test interval yielded the opposite result (Experiment 2).
      Previous data appear consistent with this observation suggesting that, although
      delayed extinction appears more beneficial in the short term, immediate
      extinction may have more favorable long-term effects. These observations may have
      important implications for attenuation of relapse in clinical situations.

PMID- 21097608
TI  - African 2, a clonal complex of Mycobacterium bovis epidemiologically important in
      East Africa.
AB  - We have identified a clonal complex of Mycobacterium bovis isolated at high
      frequency from cattle in Uganda, Burundi, Tanzania, and Ethiopia. We have named
      this related group of M. bovis strains the African 2 (Af2) clonal complex of M.
      bovis. Af2 strains are defined by a specific chromosomal deletion (RDAf2) and can
      be identified by the absence of spacers 3 to 7 in their spoligotype patterns.
      Deletion analysis of M. bovis isolates from Algeria, Mali, Chad, Nigeria,
      Cameroon, South Africa, and Mozambique did not identify any strains of the Af2
      clonal complex, suggesting that this clonal complex of M. bovis is localized in
      East Africa. The specific spoligotype pattern of the Af2 clonal complex was
      rarely identified among isolates from outside Africa, and the few isolates that
      were found and tested were intact at the RDAf2 locus. We conclude that the Af2
      clonal complex is localized to cattle in East Africa. We found that strains of
      the Af2 clonal complex of M. bovis have, in general, four or more copies of the
      insertion sequence IS6110, in contrast to the majority of M. bovis strains
      isolated from cattle, which are thought to carry only one or a few copies.

PMID- 21097609
TI  - Structural and functional insights into Aeropyrum pernix OppA, a member of a
      novel archaeal OppA subfamily.
AB  - In this study we gain insight into the structural and functional characterization
      of the Aeropyrum pernix oligopeptide-binding protein (OppA(Ap)) previously
      identified from the extracellular medium of an Aeropyrum pernix cell culture at
      late stationary phase. OppA(Ap) showed an N-terminal Q32 in a pyroglutamate form
      and C-terminal processing at the level of a threonine-rich region probably
      involved in protein membrane anchoring. Moreover, the OppA(Ap) protein released
      into the medium was identified as a "nicked" form composed of two tightly
      associated fragments detachable only under strong denaturing conditions. The
      cleavage site E569-G570 seems be located on an exposed surface loop that is
      highly conserved in several three-dimensional (3D) structures of
      dipeptide/oligopeptide-binding proteins from different sources. Structural and
      biochemical properties of the nicked protein were virtually indistinguishable
      from those of the intact form. Indeed, studies of the entire bacterially
      expressed OppA(Ap) protein owning the same N and C termini of the nicked form
      supported these findings. Moreover, in the middle exponential growth phase,
      OppA(Ap) was found as an intact cell membrane-associated protein. Interestingly,
      the native exoprotein OppA(Ap) was copurified with a hexapeptide (EKFKIV) showing
      both lysines methylated and possibly originating from an A. pernix endogenous
      stress-induced lipoprotein. Therefore, the involvement of OppA(Ap) in the
      recycling of endogenous proteins was suggested to be a potential physiological
      function. Finally, a new OppA from Sulfolobus solfataricus, SSO1288, was purified
      and preliminarily characterized, allowing the identification of a common
      structural/genetic organization shared by all "true" archaeal OppA proteins of
      the dipeptide/oligopeptide class.

PMID- 21097610
TI  - Complete genome sequence of the haloaromatic acid-degrading bacterium
      Achromobacter xylosoxidans A8.
AB  - Achromobacter xylosoxidans strain A8 was isolated from soil contaminated with
      polychlorinated biphenyls. It can use 2-chlorobenzoate and 2,5-dichlorobenzoate
      as sole sources of carbon and energy. This property makes it a good starting
      microorganism for further development toward a bioremediation tool. The genome of
      A. xylosoxidans consists of a 7-Mb chromosome and two large plasmids (98 kb and
      248 kb). Besides genes for the utilization of xenobiotic organic substrates, it
      contains genes associated with pathogenesis, toxin production, and resistance.
      Here, we report the complete genome sequence.

PMID- 21097611
TI  - Complete genome sequences of three Erwinia amylovora phages isolated in north
      america and a bacteriophage induced from an Erwinia tasmaniensis strain.
AB  - Fire blight, a plant disease of economic importance caused by Erwinia amylovora,
      may be controlled by the application of bacteriophages. Here, we provide the
      complete genome sequences and the annotation of three E. amylovora-specific
      phages isolated in North America and genomic information about a bacteriophage
      induced by mitomycin C treatment of an Erwinia tasmaniensis strain that is
      antagonistic for E. amylovora. The American phages resemble two already-described
      viral genomes, whereas the E. tasmaniensis phage displays a singular genomic
      sequence in BLAST searches.

PMID- 21097612
TI  - Differential responses of Bacillus subtilis rRNA promoters to nutritional stress.
AB  - The in vivo expression levels of four rRNA promoter pairs (rrnp(1)p(2)) of
      Bacillus subtilis were determined by employing single-copy lacZ fusions
      integrated at the amyE locus. The rrnO, rrnJ, rrnD, and rrnB promoters displayed
      unique growth rate regulation and stringent responses. Both lacZ activity and
      mRNA levels were highest for rrnO under all growth conditions tested, while rrnJ,
      rrnB, and rrnD showed decreasing levels of activity. During amino acid starvation
      induced by serine hydroxamate (SHX), only the strong rrnO and rrnJ promoters
      demonstrated stringent responses. Under the growth conditions used, the rrn
      promoters showed responses similar to the responses to carbon source limitation
      induced by alpha-methyl glucoside (alpha-MG). The ratio of P2 to P1 transcripts,
      determined by primer extension analysis, was high for the strong rrnO and rrnJ
      promoters, while only P2 transcripts were detected for the weak rrnD and rrnB
      promoters. Cloned P1 or P2 promoter fragments of rrnO or rrnJ were differentially
      regulated. In wild-type (relA(+)) and suppressor [relA(S)] strains under the
      conditions tested, only P2 responded to carbon source limitation by a decrease in
      RNA synthesis, correlating with an increase in (p)ppGpp levels and a decrease in
      the GTP concentration. The weak P1 promoter elements remain relaxed in the three
      genetic backgrounds [relA(+), relA, relA(S)] in the presence of alpha-MG. During
      amino acid starvation, P2 was stringently regulated in relA(+) and relA(S) cells,
      while only rrnJp(1) was also regulated, but to a lesser extent. Both the relA(+)
      and relA(S) strains showed (p)ppGpp accumulation after alpha-MG treatment but not
      after SHX treatment. These data reveal the complex nature of B. subtilis rrn
      promoter regulation in response to stress, and they suggest that the P2 promoters
      may play a more prominent role in the stringent response.

PMID- 21097614
TI  - Complete genome sequence of Bifidobacterium longum subsp. longum BBMN68, a new
      strain from a healthy chinese centenarian.
AB  - Bifidobacterium longum subsp. longum BBMN68 was isolated from the feces of a
      healthy centenarian living in an area of BaMa, Guangxi, China, known for
      longevity. Here we report the main genome features of B. longum strain BBMN68 and
      the identification of several predicted proteins associated with the ecological
      niche of longevity.

PMID- 21097613
TI  - Primosomal proteins DnaD and DnaB are recruited to chromosomal regions bound by
      DnaA in Bacillus subtilis.
AB  - The initiation of DNA replication requires the binding of the initiator protein,
      DnaA, to specific binding sites in the chromosomal origin of replication, oriC.
      DnaA also binds to many sites around the chromosome, outside oriC, and acts as a
      transcription factor at several of these. In low-G+C Gram-positive bacteria, the
      primosomal proteins DnaD and DnaB, in conjunction with loader ATPase DnaI, load
      the replicative helicase at oriC, and this depends on DnaA. DnaD and DnaB also
      are required to load the replicative helicase outside oriC during replication
      restart, independently of DnaA. Using chromatin immunoprecipitation, we found
      that DnaD and DnaB, but not the replicative helicase, are associated with many of
      the chromosomal regions bound by DnaA in Bacillus subtilis. This association was
      dependent on DnaA, and the order of recruitment was the same as that at oriC, but
      it was independent of a functional oriC and suggests that DnaD and DnaB do not
      require open complex formation for the stable association with DNA. These
      secondary binding regions for DnaA could be serving as a reservoir for excess
      DnaA, DnaD, and DnaB to help properly regulate replication initiation and perhaps
      are analogous to the proposed function of the datA locus in Escherichia coli.
      Alternatively, DnaD and DnaB might modulate the activity of DnaA at the secondary
      binding regions. All three of these proteins are widely conserved and likely have
      similar functions in a range of organisms.

PMID- 21097615
TI  - Genome Sequence of Weissella cibaria KACC 11862.
AB  - Weissella cibaria KACC 11862 is a Gram-positive, heterofermentative, Leuconostoc
      like lactic acid bacterium that is widely distributed in Korean traditional foods
      such as kimchi. Here we report the draft genome sequence of the type strain, W.
      cibaria KACC 11862 (1,599 known genes, 80 RNA genes), which consists of 72 large
      contigs (>100 bp in size).

PMID- 21097616
TI  - A LytM domain dictates the localization of proteins to the mother cell-forespore
      interface during bacterial endospore formation.
AB  - A large number of proteins are known to reside at specific subcellular locations
      in bacterial cells. However, the molecular mechanisms by which many of these
      proteins are anchored at these locations remains unclear. During endospore
      formation in Bacillus subtilis, several integral membrane proteins are located
      specifically at the interface of the two adjacent cells of the developing
      sporangium, the mother cell and forespore. The mother cell membrane protein
      SpoIIIAH recognizes the cell-cell interface through an interaction with the
      forespore membrane protein SpoIIQ, and then the other proteins are positioned
      there by the SpoIIIAH-SpoIIQ complex. In this study, we investigated the
      molecular mechanisms underlying the formation of the SpoIIIAH-SpoIIQ complex.
      Using gel filtration chromatography and isothermal titration calorimetry, we
      measured the binding parameters that characterize the SpoIIIAH-SpoIIQ interaction
      in vitro. We also demonstrated that the interaction of SpoIIIAH and SpoIIQ is
      governed by their YscJ and degenerate LytM domains, respectively. Therefore, the
      LytM domain of SpoIIQ provides the positional cue that dictates the localization
      of mother cell membrane proteins to the mother cell-forespore interface.

PMID- 21097617
TI  - Isolation and characterization of P1 adhesin, a leg protein of the gliding
      bacterium Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae, a pathogen causing human pneumonia, binds to solid
      surfaces at its membrane protrusion and glides by a unique mechanism. In this
      study, P1 adhesin, which functions as a "leg" in gliding, was isolated from
      mycoplasma culture and characterized. Using gel filtration, blue-native
      polyacrylamide gel electrophoresis (BN-PAGE), and chemical cross-linking, the
      isolated P1 adhesin was shown to form a complex with an accessory protein named
      P90. The complex included two molecules each of P1 adhesin and P90 (protein B),
      had a molecular mass of about 480 kDa, and was observed by electron microscopy to
      form 20-nm-diameter spheres. Partial digestion of isolated P1 adhesin by trypsin
      showed that the P1 adhesin molecule can be divided into three domains, consistent
      with the results from trypsin treatment of the cell surface. Sequence analysis of
      P1 adhesin and its orthologs showed that domain I is well conserved and that a
      transmembrane segment exists near the link between domains II and III.

PMID- 21097618
TI  - Spatial regulation of histidine kinases governing biofilm formation in Bacillus
      subtilis.
AB  - Bacillus subtilis is able to form architecturally complex biofilms on solid
      medium due to the production of an extracellular matrix. A master regulator that
      controls the expression of the genes involved in matrix synthesis is Spo0A, which
      is activated by phosphorylation via a phosphorelay involving multiple histidine
      kinases. Here we report that four kinases, KinA, KinB, KinC, and KinD, help
      govern biofilm formation but that their contributions are partially masked by
      redundancy. We show that the kinases fall into two categories and that the
      members of each pair (one pair comprising KinA and KinB and the other comprising
      KinC and KinD) are partially redundant with each other. We also show that the
      kinases are spatially regulated: KinA and KinB are active principally in the
      older, inner regions of the colony, and KinC and KinD function chiefly in the
      younger, outer regions. These conclusions are based on the morphology of kinase
      mutants, real-time measurements of gene expression using luciferase as a
      reporter, and confocal microscopy using a fluorescent protein as a reporter. Our
      findings suggest that multiple signals from the older and younger regions of the
      colony are integrated by the kinases to determine the overall architecture of the
      biofilm community.

PMID- 21097619
TI  - The peptidoglycan of Mycobacterium abscessus is predominantly cross-linked by L,D
      transpeptidases.
AB  - Few therapeutic alternatives remain for the treatment of infections due to
      multiresistant Mycobacterium abscessus. Here we show that the peptidoglycans of
      the "rough" and "smooth" morphotypes contain predominantly 3->3 cross-links
      generated by l,d-transpeptidases, indicating that these enzymes are attractive
      targets for the development of efficient drugs.

PMID- 21097620
TI  - Rok regulates yuaB expression during architecturally complex colony development
      of Bacillus subtilis 168.
AB  - Transcriptome analysis of a Bacillus subtilis rok strain that showed reduced
      complex colony structure formation revealed significant downregulation of the
      yuaB gene. Overexpression of yuaB restored structure formation in the rok strain.
      We show that transcription of yuaB is indirectly regulated by Rok, independently
      from its previously described AbrB-dependent regulation.

PMID- 21097621
TI  - Chemotaxis to the quorum-sensing signal AI-2 requires the Tsr chemoreceptor and
      the periplasmic LsrB AI-2-binding protein.
AB  - AI-2 is an autoinducer made by many bacteria. LsrB binds AI-2 in the periplasm,
      and Tsr is the l-serine chemoreceptor. We show that AI-2 strongly attracts
      Escherichia coli. Both LsrB and Tsr are necessary for sensing AI-2, but AI-2
      uptake is not, suggesting that LsrB and Tsr interact directly in the periplasm.

PMID- 21097622
TI  - The long and the short of bacterial adhesion regulation.

PMID- 21097623
TI  - Contributions of multiple binding sites and effector-independent binding to CodY
      mediated regulation in Bacillus subtilis.
AB  - CodY is a branched-chain amino acid-responsive transcriptional regulator that
      controls, directly or indirectly, the expression of more than 100 genes and
      operons in Bacillus subtilis. Using DNase I footprinting and gel-shift
      experiments, we identified two CodY-binding regions upstream of a B. subtilis
      gene (bcaP, previously known as yhdG) that encodes a transporter of branched
      chain amino acids. Mutational analysis revealed that both CodY-binding regions
      contribute to repression in vivo and do so independently of each other. Thus, a
      single CodY-binding site is apparently sufficient for substantial CodY-dependent
      regulation. By analyzing affinities of wild-type and mutant CodY-binding sites
      for CodY and their regulation by wild-type CodY and forms of CodY with various
      levels of activation by branched-chain amino acids, we concluded that unliganded
      CodY cannot repress transcription in vivo and that the level of endogenously
      produced effectors is sufficient for CodY-mediated regulation of promoters with
      stronger sites. Because the sites with higher affinity apparently respond to
      lower concentrations of CodY effectors and saturate faster as the concentrations
      of effectors increase, having two sites of binding with different affinities for
      CodY permits a promoter to respond to a wider range of intracellular
      concentrations of effectors.

PMID- 21097624
TI  - DNA-binding properties of the Bacillus subtilis and Aeribacillus pallidus AC6
      sigma(D) proteins.
AB  - sigma(D) proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound
      specifically, albeit weakly, to promoter DNA even in the absence of core RNA
      polymerase. Binding required a conserved CG motif within the -10 element, and
      this motif is known to be recognized by sigma region 2.4 and critical for
      promoter activity.

PMID- 21097625
TI  - Differences in MinC/MinD sensitivity between polar and internal Z rings in
      Escherichia coli.
AB  - In Escherichia coli the Z ring has the potential to assemble anywhere along the
      cell length but is restricted to midcell by the action of negative regulatory
      systems, including Min. In the current model for the Min system, the MinC/MinD
      division inhibitory complex is evenly distributed on the membrane and can disrupt
      Z rings anywhere in the cell; however, MinE spatially regulates MinC/MinD by
      restricting it to the cell poles, thus allowing Z ring formation at midcell. This
      model assumes that Z rings formed at different cellular locations have equal
      sensitivity to MinC/MinD in the absence of MinE. However, here we report evidence
      that differences in MinC/MinD sensitivity between polar and nonpolar Z rings
      exists even when there is no MinE. MinC/MinD at proper levels is able to block
      minicell production in Deltamin strains without increasing the cell length,
      indicating that polar Z rings are preferentially blocked. In the FtsZ-I374V
      strain (which is resistant to MinC(C)/MinD), wild-type morphology can be easily
      achieved with MinC/MinD in the absence of MinE. We also show that MinC/MinD at
      proper levels can rescue the lethal phenotype of a min slmA double deletion
      mutant, which we think is due to the elimination of polar Z rings (or FtsZ
      structures), which frees up FtsZ molecules for assembly of Z rings at internal
      sites to rescue division and growth. Taken together, these data indicate that
      polar Z rings are more susceptible to MinC/MinD than internal Z rings, even when
      MinE is absent.

PMID- 21097626
TI  - Altered regulation of the OmpF porin by Fis in Escherichia coli during an
      evolution experiment and between B and K-12 strains.
AB  - The phenotypic plasticity of global regulatory networks provides bacteria with
      rapid acclimation to a wide range of environmental conditions, while genetic
      changes in those networks provide additional flexibility as bacteria evolve
      across long time scales. We previously identified mutations in the global
      regulator-encoding gene fis that enhanced organismal fitness during a long-term
      evolution experiment with Escherichia coli. To gain insight into the effects of
      these mutations, we produced two-dimensional protein gels with strains carrying
      different fis alleles, including a beneficial evolved allele and one with an in
      frame deletion. We found that Fis controls the expression of the major porin
      encoding gene ompF in the E. coli B-derived ancestral strain used in the
      evolution experiment, a relationship that has not been described before. We
      further showed that this regulatory connection evolved over two different time
      scales, perhaps explaining why it was not observed before. On the longer time
      scale, we showed that this regulation of ompF by Fis is absent from the more
      widely studied K-12 strain and thus is specific to the B strain. On a shorter
      time scale, this regulatory linkage was lost during 20,000 generations of
      experimental evolution of the B strain. Finally, we mapped the Fis binding sites
      in the ompF regulatory region, and we present a hypothetical model of ompF
      expression that includes its other known regulators.

PMID- 21097627
TI  - Fur and the novel regulator YqjI control transcription of the ferric reductase
      gene yqjH in Escherichia coli.
AB  - Iron acquisition in aerobic habitats is complicated by the low solubility of
      ferric hydroxides. Siderophores that bind ferric iron with high affinity are used
      to mobilize iron. The reduction of ferric iron to the ferrous form can be coupled
      to the release of iron from siderophores. Iron is also stored intracellularly as
      a ferric mineral in proteins, such as ferritin, and must be reduced during
      release. In Escherichia coli, the yqjH gene encodes a putative ferric siderophore
      reductase that is also part of the Fur regulon. Here we show that YqjH has ferric
      reductase activity and is required for iron homeostasis in E. coli. Divergently
      transcribed from yqjH is the yqjI gene, which encodes a novel member of the
      winged-helix family of transcriptional regulators and also contains an N-terminal
      extension similar to the Ni(2+)-binding C-terminal tail of SlyD. Deletion of yqjI
      leads to constitutive high-level activity of the yqjH and yqjI promoters.
      Purified YqjI binds inverted repeat target sequences within the yqjH and yqjI
      promoters. We also observed that YqjI-dependent transcriptional repression is
      reduced when cells are exposed to elevated nickel levels, resulting in increased
      expression of yqjH and yqjI. YqjI binding to nickel or iron reduces YqjI DNA
      binding activity in vitro. Furthermore, we found that elevated nickel stress
      levels disrupt iron homeostasis in E. coli and that deletion of yqjH increases
      nickel toxicity. Our results suggest that the YqjI protein controls expression of
      yqjH to help maintain iron homeostasis under conditions (such as elevated
      cellular nickel levels) that disrupt iron metabolism.

PMID- 21097628
TI  - Promoter discrimination at class I MarA regulon promoters mediated by glutamic
      acid 89 of the MarA transcriptional activator of Escherichia coli.
AB  - Three paralogous transcriptional activators MarA, SoxS, and Rob, activate > 40
      Escherichia coli promoters. To understand why MarA does not activate certain
      promoters as strongly as SoxS, we compared MarA, MarA mutants, and SoxS for their
      abilities to activate 16 promoters and to bind their cognate marbox binding
      sites. Replacement of the MarA glutamic acid residue 89 with alanine greatly
      increased the marbox binding and activation of many class I promoters. Like cells
      constitutive for SoxS, cells expressing the MarA with the E89A mutation were more
      resistant to superoxides than those harboring WT MarA. The activities of several
      other E89 substitutions ranked as follows: E89A > E89G > E89V > WT > E89D.
      Increased binding and activation occurred only at class I promoters when the 12th
      base of the promoter's marbox (a position at which there is no known interaction
      between the marbox and MarA) was not a T residue. Furthermore, WT MarA binding to
      a synthetic marbox in vitro was enhanced when the phosphate group between
      positions 12 and 13 was eliminated on one strand. The results demonstrate that
      relatively minor changes in a single amino acid side chain (e.g., alanine to
      valine or glutamic acid to aspartic acid) can strongly influence activity despite
      any evidence that the side chain is involved in positive interactions with either
      DNA or RNA polymerase. We present a model which attributes the differences in
      binding and activation to the interference between the beta- and gamma-carbons of
      the amino acid at position 89 and the phosphate group between positions 12 and
      13.

PMID- 21097629
TI  - Genome copy numbers and gene conversion in methanogenic archaea.
AB  - Previous studies revealed that one species of methanogenic archaea,
      Methanocaldococcus jannaschii, is polyploid, while a second species,
      Methanothermobacter thermoautotrophicus, is diploid. To further investigate the
      distribution of ploidy in methanogenic archaea, species of two additional genera
      Methanosarcina acetivorans and Methanococcus maripaludis-were investigated. M.
      acetivorans was found to be polyploid during fast growth (t(D) = 6 h; 17 genome
      copies) and oligoploid during slow growth (doubling time = 49 h; 3 genome
      copies). M. maripaludis has the highest ploidy level found for any archaeal
      species, with up to 55 genome copies in exponential phase and ca. 30 in
      stationary phase. A compilation of archaeal species with quantified ploidy levels
      reveals a clear dichotomy between Euryarchaeota and Crenarchaeota: none of seven
      euryarchaeal species of six genera is monoploid (haploid), while, in contrast,
      all six crenarchaeal species of four genera are monoploid, indicating significant
      genetic differences between these two kingdoms. Polyploidy in asexual species
      should lead to accumulation of inactivating mutations until the number of intact
      chromosomes per cell drops to zero (called "Muller's ratchet"). A mechanism to
      equalize the genome copies, such as gene conversion, would counteract this
      phenomenon. Making use of a previously constructed heterozygous mutant strain of
      the polyploid M. maripaludis we could show that in the absence of selection very
      fast equalization of genomes in M. maripaludis took place probably via a gene
      conversion mechanism. In addition, it was shown that the velocity of this
      phenomenon is inversely correlated to the strength of selection.

PMID- 21097630
TI  - Membrane topology and DNA-binding ability of the Streptococcal CpsA protein.
AB  - Many streptococcal pathogens require a polysaccharide capsule for survival in the
      host during systemic infection. The highly conserved CpsA protein is proposed to
      be a transcriptional regulator of capsule production in streptococci, although
      the regulatory mechanism is unknown. Hydropathy plots of CpsA predict an integral
      membrane protein with 3 transmembrane domains and only 27 cytoplasmic residues,
      whereas other members of the LytR_cpsA_psr protein family are predicted to have a
      single transmembrane domain. This unique topology, with the short cytoplasmic
      domain, membrane localization, and large extracellular domain, suggests a novel
      mechanism of transcriptional regulation. Therefore, to determine the actual
      membrane topology of CpsA, specific protein domains were fused to beta
      galactosidase or alkaline phosphatase. Enzymatic assays confirmed that the
      predicted membrane topology for CpsA is correct. To investigate how this integral
      membrane protein may be functioning in regulation of capsule transcription,
      purified full-length and truncated forms of CpsA were used in electrophoretic
      mobility shift assays to characterize the ability to bind the capsule operon
      promoter. Assays revealed that full-length, purified CpsA protein binds
      specifically to DNA containing the capsule promoter region. Furthermore, the
      large extracellular domain is not required for DNA binding, but all cytoplasmic
      regions of CpsA are necessary and sufficient for specific binding to the capsule
      operon promoter. This is the first demonstration of a member of this protein
      family interacting with its target DNA. Taken together, CpsA, as well as other
      members of the LytR_cpsA_psr protein family, appears to utilize a unique
      mechanism of transcriptional regulation.

PMID- 21097631
TI  - Identification of nocobactin NA biosynthetic gene clusters in Nocardia farcinica.
AB  - We identified the biosynthetic gene clusters of the siderophore nocobactin NA.
      The nbt clusters, which were discovered as genes highly homologous to the
      mycobactin biosynthesis genes by the genomic sequencing of Nocardia farcinica IFM
      10152, consist of 10 genes separately located at two genomic regions. The gene
      organization of the nbt clusters and the predicted functions of the nbt genes,
      particularly the cyclization and epimerization domains, were in good agreement
      with the chemical structure of nocobactin NA. Disruptions of the nbtA and nbtE
      genes, respectively, reduced and abolished the productivity of nocobactin NA. The
      heterologous expression of the nbtS gene revealed that this gene encoded a
      salicylate synthase. These results indicate that the nbt clusters are responsible
      for the biosynthesis of nocobactin NA. We also found putative IdeR-binding
      sequences upstream of the nbtA, -G, -H, -S, and -T genes, whose expression was
      more than 10-fold higher in the low-iron condition than in the high-iron
      condition. These results suggest that nbt genes are regulated coordinately by
      IdeR protein in an iron-dependent manner. The DeltanbtE mutant was found to be
      impaired in cytotoxicity against J774A.1 cells, suggesting that nocobactin NA
      production is required for virulence of N. farcinica.

PMID- 21097632
TI  - Acyl-homoserine lactone binding to and stability of the orphan Pseudomonas
      aeruginosa quorum-sensing signal receptor QscR.
AB  - The Pseudomonas aeruginosa transcription factor QscR responds to a variety of
      fatty acyl-homoserine lactones (HSLs), including N-3-oxododecanoyl-HSL (3OC12
      HSL), which is produced and detected by the P. aeruginosa quorum-sensing circuit
      LasI and LasR. As is true for LasR and many other acyl-HSL-dependent
      transcription factors, production of soluble QscR in sufficient amounts for
      purification requires growth of recombinant bacteria in the presence of an
      appropriate acyl-HSL. QscR is thought to bind 3OC12-HSL relatively weakly
      compared to LasR, and unlike LasR, binding of purified QscR to target DNA was
      shown to strongly depend on exogenously added 3OC12-HSL. We show that purified
      QscR is dimeric at sufficiently high concentrations and monomeric at lower
      concentrations. Furthermore, QscR bound 3OC12-HSL more tightly than previously
      believed. Purified QscR retained 3OC12-HSL, and at sufficiently high
      concentrations, it bound target DNA in the absence of added 3OC12-HSL. We also
      obtained soluble QscR from recombinant Escherichia coli grown in the presence of
      N-3-oxohexanoyl-HSL (3OC6-HSL) instead of 3OC12-HSL, and because 3OC6-HSL bound
      much more loosely to QscR than other acyl-HSLs tested, we were able to exchange
      3OC6-HSL with other acyl-HSLs in vitro and then estimate binding affinities of
      QscR for different acyl-HSLs and for target DNA. Our data support a model whereby
      QscR polypeptides fold properly in the absence of an acyl-HSL, but soluble, acyl
      HSL-free QscR does not accumulate because it is subject to rapid aggregation or
      proteolysis.

PMID- 21097634
TI  - Role of the F1 region in the Escherichia coli aerotaxis receptor Aer.
AB  - In Escherichia coli, the aerotaxis receptor Aer is an atypical receptor because
      it senses intracellular redox potential. The Aer sensor is a cytoplasmic, N
      terminal PAS domain that is tethered to the membrane by a 47-residue F1 linker.
      Here we investigated the function, topology, and orientation of F1 by employing
      random mutagenesis, cysteine scanning, and disulfide cross-linking. No native
      residue was obligatory for function, most deleterious substitutions had radically
      different side chain properties, and all F1 mutants but one were functionally
      rescued by the chemoreceptor Tar. Cross-linking studies were consistent with the
      predicted alpha-helical structure in the N-terminal F1 region and demonstrated
      trigonal interactions among the F1 linkers from three Aer monomers, presumably
      within trimer-of-dimer units, as well as binary interactions between subunits.
      Using heterodimer analyses, we also demonstrated the importance of arginine
      residues near the membrane interface, which may properly anchor the Aer protein
      in the membrane. By incorporating these data into a homology model of Aer, we
      developed a model for the orientation of the Aer F1 and PAS regions in an Aer
      lattice that is compatible with the known dimensions of the chemoreceptor
      lattice. We propose that the F1 region facilitates the orientation of PAS and
      HAMP domains during folding and thereby promotes the stability of the PAS and
      HAMP domains in Aer.

PMID- 21097633
TI  - Genome annotation and intraviral interactome for the Streptococcus pneumoniae
      virulent phage Dp-1.
AB  - Streptococcus pneumoniae causes several diseases, including pneumonia,
      septicemia, and meningitis. Phage Dp-1 is one of the very few isolated virulent
      S. pneumoniae bacteriophages, but only a partial characterization is currently
      available. Here, we confirmed that Dp-1 belongs to the family Siphoviridae. Then,
      we determined its complete genomic sequence of 56,506 bp. It encodes 72 open
      reading frames, of which 44 have been assigned a function. We have identified
      putative promoters, Rho-independent terminators, and several genomic clusters. We
      provide evidence that Dp-1 may be using a novel DNA replication system as well as
      redirecting host protein synthesis through queuosine-containing tRNAs. Liquid
      chromatography-mass spectrometry analysis of purified phage Dp-1 particles
      identified at least eight structural proteins. Finally, using comprehensive yeast
      two-hybrid screens, we identified 156 phage protein interactions, and this
      intraviral interactome was used to propose a structural model of Dp-1.

PMID- 21097636
TI  - Zobellella aerophila sp. nov., isolated from seashore sand, and emended
      description of the genus Zobellella.
AB  - A strictly aerobic, nitrate-reducing, motile, rod-shaped member of the class
      Gammaproteobacteria, designated strain JC2671(T), was isolated from a seashore
      sand sample from Dokdo, Korea. The isolate reduced nitrate to nitrite, but not to
      nitrogen, and required NaCl for growth. 16S rRNA gene sequence analysis indicated
      that the isolate belonged to the genus Zobellella within the order
      Alteromonadales with sequence similarities of 96.0-97.6 % to strains of
      Zobellella species with validly published names. However, in DNA-DNA
      hybridization studies, a low genomic relatedness (43 %) between strain JC2671(T)
      and the type strain of Zobellella denitrificans indicated that the isolate
      represented a novel genomic species. The polar lipid pattern
      (phosphatidylethanolamine and phosphatidylglycerol), predominant cellular fatty
      acids [C(16 : 0), summed feature 3 (C(16 : 1)omega6c and/or C(16 : 1)omega7c) and
      summed feature 8 (C(18 : 1)omega6c and/or C(18 : 1)omega7c)] and the DNA G+C
      content (59 mol%) of the novel strain were consistent with its assignment to the
      genus Zobellella. In contrast, a number of phenotypic characteristics, namely a
      requirement of NaCl for growth, the inability to grow under facultatively
      anaerobic conditions, the absence of nitrite reduction and differences in
      carbohydrate utilization and enzymic activities, clearly distinguished the novel
      isolate from other species of the genus Zobellella. Data from this polyphasic
      study indicate that strain JC2671(T) represents a novel species in the genus
      Zobellella, for which the name Zobellella aerophila sp. nov. is proposed. The
      type strain is JC2671(T) ( = KACC 15081(T)  = JCM 17110(T)). The description of
      the genus Zobellella has been emended accordingly.

PMID- 21097635
TI  - The peptidoglycan-binding protein FimV promotes assembly of the Pseudomonas
      aeruginosa type IV pilus secretin.
AB  - The Pseudomonas aeruginosa inner membrane protein FimV is among several proteins
      of unknown function required for type IV pilus-mediated twitching motility,
      arising from extension and retraction of pili from their site of assembly in the
      inner membrane. The pili transit the periplasm and peptidoglycan (PG) layer,
      ultimately exiting the cell through the PilQ secretin. Although fimV mutants are
      nonmotile, they are susceptible to killing by pilus-specific bacteriophage, a
      hallmark of retractable surface pili. Here we show that levels of recoverable
      surface pili were markedly decreased in fimV pilT retraction-deficient mutants
      compared with levels in the pilT control, demonstrating that FimV acts at the
      level of pilus assembly. Levels of inner membrane assembly subcomplex proteins
      PilM/N/O/P were decreased in fimV mutants, but supplementation of these
      components in trans did not restore pilus assembly or motility. Loss of FimV
      dramatically reduced the levels of the PilQ secretin multimer through which pili
      exit the cell, in part due to decreased levels of PilQ monomers, while PilF
      pilotin levels were unchanged. Expression of pilQ in trans in the wild type or
      fimV mutants increased total PilQ monomer levels but did not alter secretin
      multimer levels or motility. PG pulldown assays showed that the N terminus of
      FimV bound PG in a LysM motif-dependent manner, and a mutant with an in-frame
      chromosomal deletion of the LysM motif had reduced motility, secretin levels, and
      surface piliation. Together, our data show that FimV's role in pilus assembly is
      to promote secretin formation and that this function depends upon its PG-binding
      domain.

PMID- 21097637
TI  - Cyanobacterial systematics and nomenclature as featured in the International
      Bulletin of Bacteriological Nomenclature and Taxonomy / International Journal of
      Systematic Bacteriology / International Journal of Systematic and Evolutionary
      Microbiology.
AB  - Surprisingly few papers on cyanobacteria have been published in the International
      Bulletin of Bacteriological Nomenclature and Taxonomy / International Journal of
      Systematic Bacteriology / International Journal of Systematic and Evolutionary
      Microbiology (IBBNT/IJSB/IJSEM) during its 60&emsp14;years of existence. The
      first papers featuring the group appeared in volume 28 and, in the
      32&emsp14;years that have passed since, 42 articles on cyanobacteria have been
      published in the journal. Very few of these papers deal with the description of
      new taxa and this is understandable in view of the current difficulty in validly
      publishing new names of cyanobacteria under the rules of the International Code
      of Nomenclature of Prokaryotes (ICNP). Other papers discuss the problems of the
      nomenclature of the group under the International Code of Botanical Nomenclature
      (ICBN)/ICNP and the ICBN. The largest group of articles on cyanobacteria consists
      of papers on systematics, in which isolates are compared using different
      approaches, without any implications for the nomenclature of the group under
      either Code. The fact that on average these papers have been highly cited shows
      that IJSEM and its predecessors have been an excellent framework for publications
      on cyanobacteria and should remain so in the future.

PMID- 21097638
TI  - Methyloferula stellata gen. nov., sp. nov., an acidophilic, obligately
      methanotrophic bacterium that possesses only a soluble methane monooxygenase.
AB  - Two strains of aerobic methanotrophic bacteria, AR4(T) and SOP9, were isolated
      from acidic (pH 3.8-4.0) Sphagnum peat bogs in Russia. Another phenotypically
      similar isolate, strain LAY, was obtained from an acidic (pH 4.0) forest soil in
      Germany. Cells of these strains were Gram-negative, non-pigmented, non-motile,
      thin rods that multiplied by irregular cell division and formed rosettes or
      amorphous cell conglomerates. Similar to Methylocella species, strains AR4(T),
      SOP9 and LAY possessed only a soluble form of methane monooxygenase (sMMO) and
      lacked intracytoplasmic membranes. Growth occurred only on methane and methanol;
      the latter was the preferred growth substrate. mRNA transcripts of sMMO were
      detectable in cells when either methane or both methane and methanol were
      available. Carbon was assimilated via the serine and ribulose-bisphosphate (RuBP)
      pathways; nitrogen was fixed via an oxygen-sensitive nitrogenase. Strains AR4(T),
      SOP9 and LAY were moderately acidophilic, mesophilic organisms capable of growth
      between pH 3.5 and 7.2 (optimum pH 4.8-5.2) and at 4-33  degrees C (optimum 20-23
      degrees C). The major cellular fatty acid was 18 : 1omega7c and the quinone was
      Q-10. The DNA G+C content was 55.6-57.5 mol%. The isolates belonged to the family
      Beijerinckiaceae of the class Alphaproteobacteria and were most closely related
      to the sMMO-possessing methanotrophs of the genus Methylocella (96.4-97.0 % 16S
      rRNA gene sequence similarity), particulate MMO (pMMO)-possessing methanotrophs
      of the genus Methylocapsa (96.1-97.0 %), facultative methylotrophs of the genus
      Methylovirgula (96.1-96.3 %) and non-methanotrophic organotrophs of the genus
      Beijerinckia (96.5-97.0 %). Phenotypically, strains AR4(T), SOP9 and LAY were
      most similar to Methylocella species, but differed from members of this genus by
      cell morphology, greater tolerance of low pH, detectable activities of RuBP
      pathway enzymes and inability to grow on multicarbon compounds. Therefore, we
      propose a novel genus and species, Methyloferula stellata gen. nov., sp. nov., to
      accommodate strains AR4(T), SOP9 and LAY. Strain AR4(T) ( = DSM 22108(T)  = LMG
      25277(T)  = VKM B-2543(T)) is the type strain of Methyloferula stellata.

PMID- 21097639
TI  - Schleiferia thermophila gen. nov., sp. nov., a slightly thermophilic bacterium of
      the phylum 'Bacteroidetes' and the proposal of Schleiferiaceae fam. nov.
AB  - A bacterial isolate, with an optimum growth temperature of about 50  degrees C
      and an optimum pH for growth between 7.5 and 8.5, was recovered from a hot spring
      in the Furnas area of the Island of Sao Miguel in the Azores. The novel isolate
      is orange-pigmented, forms non-motile, rod-shaped cells that stain Gram-negative,
      is strictly aerobic, oxidase-positive and catalase-negative. The major fatty
      acids of strain TU-20(T) are 16 : 1omega6c, 17 : 0 iso 3-OH and 15 : 0 iso.
      Menaquinone 6 is the major respiratory quinone. Based on 16S rRNA gene sequence
      analysis, physiological and biochemical characteristics, we describe a novel
      species of a novel genus represented by strain TU-20(T) ( = DSM 21410(T ) = LMG
      24594(T)) for which we propose the name Schleiferia thermophila gen nov., sp.
      nov. We also propose the family Schleiferiaceae fam. nov. to accommodate this new
      genus.

PMID- 21097640
TI  - Snuella lapsa gen. nov., sp. nov., isolated from tidal flat sediment.
AB  - A yellow-coloured, rod-shaped, Gram-reaction-negative, aerobic bacterial strain,
      designated JC2132(T), was isolated from a tidal flat sediment sample from Ganghwa
      Island, Korea. The isolate required sea salts for growth. Cells produced non
      diffusible carotenoid pigments, but flexirubin-type pigments were absent. Gliding
      motility was observed. Phylogenetic analyses based on 16S rRNA gene sequences
      showed that strain JC2132(T) represented a distinct phyletic line that reflected
      a novel generic status within the family Flavobacteriaceae with relatively low
      sequence similarities (<95 %) to members of other genera with validly published
      names. The predominant isoprenoid quinone (MK-6) and DNA G+C content (35 mol%)
      were consistent with assignment of the isolate to the family Flavobacteriaceae,
      but overall phenotypic traits demonstrated that strain JC2132(T) was not closely
      affiliated with any previously described genera. Based on taxonomic data obtained
      using a polyphasic approach, it is proposed that strain JC2132(T) represents a
      novel species in a new genus belonging to the family Flavobacteriaceae, for which
      the name Snuella lapsa gen. nov., sp. nov. is proposed; the type strain of the
      type species is JC2132(T) ( = KACC 14152(T) = JCM 17111(T)).

PMID- 21097641
TI  - Chthonomonas calidirosea gen. nov., sp. nov., an aerobic, pigmented, thermophilic
      micro-organism of a novel bacterial class, Chthonomonadetes classis nov., of the
      newly described phylum Armatimonadetes originally designated candidate division
      OP10.
AB  - An aerobic, saccharolytic, obligately thermophilic, motile, non-spore-forming
      bacterium, strain T49(T), was isolated from geothermally heated soil at Hell's
      Gate, Tikitere, New Zealand. On the basis of 16S rRNA gene sequence similarity,
      T49(T) is the first representative of a new class in the newly described phylum
      Armatimonadetes, formerly known as candidate division OP10. Cells of strain
      T49(T) stained Gram-negative and were catalase-positive and oxidase-negative.
      Cells possessed a highly corrugated outer membrane. The major fatty acids were 16
      : 0, i17 : 0 and ai17 : 0. The G+C content of the genomic DNA was 54.6 mol%.
      Strain T49(T) grew at 50-73  degrees C with an optimum temperature of 68  degrees
      C, and at pH 4.7-5.8 with an optimum growth pH of 5.3. A growth rate of 0.012 h(
      1) was observed under optimal temperature and pH conditions. The primary
      respiratory quinone was MK-8. Optimal growth was achieved in the absence of NaCl,
      although growth was observed at NaCl concentrations as high as 2 % (w/v). Strain
      T49(T) was able to utilize mono- and disaccharides such as cellobiose, lactose,
      mannose and glucose, as well as branched or amorphous polysaccharides such as
      starch, CM-cellulose, xylan and glycogen, but not highly linear polysaccharides
      such as crystalline cellulose or cotton. On the basis of its phylogenetic
      position and phenotypic characteristics, we propose that strain T49(T) represents
      a novel bacterial genus and species within the new class Chthonomonadetes classis
      nov. of the phylum Armatimonadetes. The type strain of Chthonomonas calidirosea
      gen. nov., sp. nov. is T49(T) ( = DSM 23976(T) = ICMP 18418(T)).

PMID- 21097642
TI  - Pontirhabdus pectinivorans gen. nov., sp. nov., isolated from seawater.
AB  - A yellow-coloured, rod-shaped, Gram-reaction-negative and aerobic bacterial
      strain, designated JC2675(T), was isolated from a seawater sample from Jeju
      Island, Korea. The isolate required sea salts for growth. Gliding motility was
      observed. Flexirubin-type pigments were absent. Phylogenetic analyses based on
      16S rRNA gene sequences showed that strain JC2675(T) represented a distinct
      phyletic line that reflected a novel generic status within the family
      Flavobacteraceae with relatively low gene sequence similarities (<95.7 %) to
      other recognized genera. The predominant isoprenoid quinone (MK-6) and DNA G+C
      content (30 mol%) were consistent with the assignment of the novel strain to the
      family Flavobacteriaceae, but overall phenotypic traits demonstrated that the
      novel strain was not closely affiliated with any previously described genus.
      Based on data from a study using a polyphasic taxonomic approach, it is proposed
      that strain JC2675(T) represents a new genus and novel species belonging to the
      family Flavobacteriaceae, for which the name Pontirhabdus pectinivorans gen.
      nov., sp. nov. is proposed. The type strain of the type species is JC2675(T) ( =
      KACC 14153(T) = JCM 17107(T)).

PMID- 21097643
TI  - Novosphingobium sediminicola sp. nov. isolated from freshwater sediment.
AB  - A yellow-pigmented, Gram-negative, short rod-shaped, non-motile and non-spore
      forming bacterial strain, designated HU1-AH51(T), was isolated from freshwater
      sediment and was characterized using a polyphasic approach, in order to determine
      its taxonomic position. On the basis of 16S rRNA gene sequence similarity, strain
      HU1-AH51(T) was shown to belong to the genus Novosphingobium, showing the highest
      level of sequence similarity with respect to Novosphingobium resinovorum NCIMB
      8767(T) (96.0 %), Novosphingobium naphthalenivorans TUT562(T) (96.0 %) and
      Novosphingobium panipatense SM16(T) (96.0 %). Strain HU1-AH51(T) had a genomic
      DNA G+C content of 62.6 mol% and Q-10 as the predominant respiratory quinone.
      Furthermore, the major polyamine component (spermidine) in the cytoplasm and the
      presence of sphingoglycolipids suggested that strain HU1-AH51(T) belongs to the
      family Sphingomonadaceae. On the basis of its phenotypic properties and
      phylogenetic distinctiveness, strain HU1-AH51(T) represents a novel species of
      the genus Novosphingobium, for which the name Novosphingobium sediminicola sp.
      nov. is proposed. The type strain is HU1-AH51(T) ( = LMG 24320(T)  = KCTC
      22311(T)).

PMID- 21097644
TI  - AKT1 G205T genotype influences obesity-related metabolic phenotypes and their
      responses to aerobic exercise training in older Caucasians.
AB  - As part of the insulin signalling pathway, Akt influences growth and metabolism.
      The AKT1 gene G205T (rs1130214) polymorphism has potential functional effects.
      Thus, we determined whether the G205T polymorphism influences metabolic variables
      and their responses to aerobic exercise training. Following dietary
      stabilization, healthy, sedentary, 50- to 75-year-old Caucasian men (n = 51) and
      women (n = 58) underwent 6 months of aerobic exercise training. Before and after
      completing the intervention, dual-energy X-ray absorptiometry was used to measure
      percentage body fat, computed tomography to measure visceral and subcutaneous
      fat, and oral glucose tolerance testing to measure glucose total area under the
      curve (AUC), insulin AUC and insulin sensitivity. Taqman assay was used to
      determine AKT1 G205T genotypes. At baseline, men with the GG genotype (n = 29)
      had lower maximal oxygen consumption (VO2 max) values (P = 0.026) and higher
      percentage body fat (P = 0.046), subcutaneous fat (P = 0.021) and insulin AUC (P
      = 0.003) values than T allele carriers (n = 22). Despite their rather
      disadvantageous starting values, men with the GG genotype seemed to respond to
      exercise training more robustly than men with the T allele, highlighted by
      significantly greater fold change improvements in insulin AUC (P = 0.012) and
      glucose AUC (P = 0.035). Although the GG group also significantly improved VO2
      max with training, the change in VO2 max was not as great as that of the T allele
      carriers (P = 0.037). In contrast, after accounting for hormone replacement
      therapy use, none of the variables differed in the women at baseline. As a result
      of exercise training, women with the T allele (n = 20) had greater fold change
      improvements in fasting glucose (P = 0.011), glucose AUC (P = 0.017) and insulin
      sensitivity (P = 0.044) than GG genotype women (n = 38). Our results suggest that
      the AKT1 G205T polymorphism influences metabolic variables and their responses to
      aerobic exercise training in older, previously sedentary individuals.

PMID- 21097645
TI  - Angiotensin AT1 receptors in paraventricular nucleus contribute to sympathetic
      activation and enhanced cardiac sympathetic afferent reflex in renovascular
      hypertensive rats.
AB  - Sympathetic activity is enhanced in hypertension, which contributes to the
      pathogenesis of hypertension and progression of organ damage. The cardiac
      sympathetic afferent reflex (CSAR) is enhanced in renovascular hypertension and
      involved in the sympathetic activation. The present study was designed to
      investigate whether angiotensin II (Ang II) and Ang II type 1 (AT(1)) receptors
      in paraventricular nucleus (PVN) contribute to the enhanced CSAR and sympathetic
      outflow in experimental renovascular hypertensive rats. Hypertension was induced
      by the two-kidney one-clip (2K1C) method. The normotensive rats underwent sham
      operation (Sham). Acute experimentation was carried out at the end of the 4th
      week. Under urethane and alpha-chloralose anaesthesia, the renal sympathetic
      nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in rats with
      sino-aortic denervation and cervical vagotomy. The AT(1) receptor expression was
      determined with Western blot. The CSAR was evaluated by the response of RSNA and
      MAP to epicardial application of 1.0 nmol of capsaicin. The AT(1) receptor
      expression in the PVN was increased, and Ang II in the PVN augmented the enhanced
      CSAR and RSNA in 2K1C rats. The effects of Ang II were abolished by pretreatment
      with the AT(1) receptor antagonist, losartan, in 2K1C rats. Losartan in the PVN
      normalized the enhanced CSAR and decreased the RSNA and MAP in 2K1C rats. These
      results indicate that the increased activity of AT(1) receptors in the PVN
      contributes to the enhanced CSAR and excessive sympathetic activation in
      renovascular hypertensive rats.

PMID- 21097646
TI  - Decreased prevalence and incidence of HCV markers in haemodialysis units: a
      multicentric French survey.
AB  - BACKGROUND: A variety of epidemiological data provide evidence for the nosocomial
      transmission of hepatitis C virus (HCV) infections to haemodialysis patients. We
      conducted a multicentric study to determine the prevalence and incidence of HCV
      infection in French haemodialysis units. METHODS: Patients undergoing chronic
      haemodialysis in 56 French units (4718 patients) were systematically screened for
      anti-HCV antibodies using third-generation tests. The incidence was estimated by
      detecting HCV RNA in seronegative patients using a standardized real-time PCR
      assay on pooled samples. RESULTS: Testing for HCV antibodies identified 361
      patients with anti-HCV antibodies, giving a prevalence of 7.7%. Multivariate
      analysis demonstrated that anti-HCV status was linked to the time on
      haemodialysis, previous kidney transplantation and the presence of anti-HBc
      antibodies, whereas erythropoietin therapy and carrying out dialysis in dedicated
      spaces seem to protect against HCV infection. Only two of the 4357 patients
      without anti-HCV antibodies tested positive for HCV RNA, giving an estimated
      incidence of 0.05% new HCV infections/year. Molecular analyses indicated that the
      two patients probably acquired HCV outside the haemodialysis unit. CONCLUSION:
      This decreased prevalence and incidence emphasizes the importance of adhering to
      the recommended universal infection-control precautions. Virological follow-up
      based on detecting anti-HCV antibodies with sensitive, specific new-generation
      serological tests could be adequate for dialysis units with few HCV infections.
      However, new infections in haemodialysis units should be identified by
      determining the HCV RNA status of seronegative patients. Standardized real-time
      PCR assays, plus pooling serum samples, make this a promising method for large
      scale epidemiological studies.

PMID- 21097647
TI  - Does a plain X-ray of the pelvis predict arterial complications in renal
      transplantation? A prospective study.
AB  - BACKGROUND: It is unknown whether if a plain X-ray of the iliac arteries (pelvic
      X-ray) is a reliable tool to detect calcifications and predict vascular
      complications. METHODS: In a prospective study, a pelvic X-ray was performed
      before transplantation in patients without evidence of peripheral vascular
      disease (n = 109) and vascular calcifications were scored. Vascular
      calcifications in the iliac arteries and complications were scored by the
      transplant surgeon during the operation (gold standard). RESULTS: Vascular
      calcifications were found on the pelvic X-ray in 33 patients (30.2%). The
      transplant surgeon identified vascular calcifications in 35%. Sensitivity and
      specificity of the pelvic X-ray for vascular calcifications in the iliac arteries
      were 48 and 82%, respectively. Technical problems with the arterial anastomosis
      due to vascular calcifications were observed in five patients. The negative
      predictive value and positive predictive value of a pelvic X-ray for
      complications with the arterial anastomosis were 99 and 14%, respectively.
      CONCLUSIONS: A pelvic X-ray is not a reliable tool to detect vascular
      calcifications. Technical problems with the arterial anastomosis due to
      calcifications are infrequent in the absence of vascular calcifications on the
      pelvic X-ray.

PMID- 21097648
TI  - Kidney transplantation improves arterial function measured by pulse wave analysis
      and endothelium-independent dilatation in uraemic patients despite deterioration
      of glucose metabolism.
AB  - BACKGROUND: The aim of this study is to investigate the effect of kidney
      transplantation on arterial function in relation to changes in glucose
      metabolism. METHODS: Included were 40 kidney recipients (Tx group, age 38 +/- 13
      years) and 40 patients without known diabetes remaining on the waiting list for
      kidney transplantation (uraemic control group, age 47 +/- 11 years). Arterial
      function was estimated by the pulse wave velocity (PWV) of the carotid-femoral
      pulse wave, aortic augmentation index (AIX), flow-mediated (FMD) and
      nitroglycerin-induced vasodilatation (NID) of the brachial artery performed
      before transplantation and after 12 months. PWV recorded sequentially at the
      carotid and femoral artery is an estimate of arterial stiffness; AIX is an
      integrated index of vascular and ventricular function. FMD and NID are the
      dilatory capacities of the brachial artery after increased flow (endothelium
      dependent) and after nitroglycerin administration (endothelium independent). The
      insulin resistance was estimated by the insulin sensitivity index (ISI). RESULTS:
      AIX was reduced from 27% (17-33) to 14% (7-25) (P = 0.01) after 1 year in the Tx
      group and remained stable in uraemic controls (P = 0.001, between groups), and
      NID increased from 11% (7-16) to 18% (12-23) (P = 0.0005). At baseline, carotid
      femoral PWV was similar in the Tx group, uraemic controls and healthy controls
      and it did not change significantly after transplantation. ISI deteriorated in
      the Tx group from 7.2 +/- 4.0 to 5.0 +/- 3.0 (P = 0.005) and remained stable in
      uraemic controls (7.9 +/- 5.1 vs 8.5 +/- 4.9, NS). Mean arterial blood pressure
      decreased from 105 +/- 13 to 96 +/- 11 mmHg (P = 0.005) in the Tx group despite a
      20% lower use of antihypertensive agents. CONCLUSIONS: Arterial function measured
      by AIX and NID was improved 1 year after kidney transplantation. This was
      associated with a decline in blood pressure and seen inspite of an increase in
      insulin resistance.

PMID- 21097649
TI  - Peritoneal clearance and transport of methylglyoxal.

PMID- 21097651
TI  - The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets and
      colorectal cancer.
AB  - BACKGROUND: Although the Mediterranean diet has been studied for cancer mortality
      and the Dietary Approaches to Stop Hypertension (DASH) diet shares similarities
      with the Mediterranean diet, few studies have specifically examined these 2 diets
      and incident colorectal cancer. OBJECTIVE: The objective was to prospectively
      assess the association between the Alternate Mediterranean Diet (aMed) and the
      DASH-style diet scores and risk of colorectal cancer in middle-aged men and
      women. DESIGN: A total of 87,256 women and 45,490 men (age 30-55 y for women and
      40-75 y for men at baseline) without a history of cancer were followed for <= 26
      y. The aMed and DASH scores were calculated for each participant by using dietary
      information that was assessed <= 7 times during follow-up. Relative risks (RRs)
      for colorectal cancer were computed with adjustment for potential confounders.
      RESULTS: We documented 1432 cases of incident colorectal cancer among women and
      1032 cases in men. Comparing top with bottom quintiles of the DASH score, the
      pooled RR for total colorectal cancer was 0.80 (95% CI: 0.70, 0.91; P for trend =
      0.0001). The corresponding RR for DASH score and colon cancer was 0.81 (95% CI:
      0.69, 0.95; P for trend = 0.002). There was a suggestion of an inverse
      association with rectal cancer with a pooled RR of 0.73 (95% CI: 0.55, 0.98; P
      for trend = 0.31) when comparing top with bottom quintiles of DASH score. No
      association was observed with aMed score. CONCLUSION: Adherence to the DASH diet
      (which involves higher intakes of whole grains, fruit, and vegetables; moderate
      amounts of low-fat dairy; and lower amounts of red or processed meats, desserts,
      and sweetened beverages) was associated with a lower risk of colorectal cancer.

PMID- 21097653
TI  - An anatomical and temporal portrait of physiological substrates for fatty acid
      amide hydrolase.
AB  - Fatty acid amide hydrolase (FAAH) regulates amidated lipid transmitters,
      including the endocannabinoid anandamide and its N-acyl ethanolamine (NAE)
      congeners and transient receptor potential channel agonists N-acyl taurines
      (NATs). Using both the FAAH inhibitor PF-3845 and FAAH(-/-) mice, we present a
      global analysis of changes in NAE and NAT metabolism caused by FAAH disruption in
      central and peripheral tissues. Elevations in anandamide (and other NAEs) were
      tissue dependent, with the most dramatic changes occurring in brain, testis, and
      liver of PF-3845-treated or FAAH(-/-) mice. Polyunsaturated NATs accumulated to
      very high amounts in the liver, kidney, and plasma of these animals. The NAT
      profile in brain tissue was markedly different and punctuated by significant
      increases in long-chain NATs found exclusively in FAAH(-/-), but not in PF-3845
      treated animals. Suspecting that this difference might reflect a slow pathway for
      NAT biosynthesis, we treated mice chronically with PF-3845 for 6 days and
      observed robust elevations in brain NATs. These studies, taken together, define
      the anatomical and temporal features of FAAH-mediated NAE and NAT metabolism,
      which are complemented and probably influenced by kinetically distinguishable
      biosynthetic pathways that produce these lipids in vivo.

PMID- 21097654
TI  - Cytochrome P450-mediated pulmonary metabolism of carcinogens: regulation and
      cross-talk in lung carcinogenesis.
AB  - Lung cancer is strongly associated with exogenous risk factors, in particular
      tobacco smoking and asbestos exposure. New research data are accumulating about
      the regulation of the metabolism of tobacco carcinogens and the metabolic
      response to oxidative stress. These data provide mechanistic details about why
      well known risk factors cause lung cancer. The purpose of this review is to
      evaluate the present knowledge of the role of cytochrome P450 (CYP) enzymes in
      the metabolism of tobacco carcinogens and associations with tobacco and asbestos
      carcinogenesis. Major emphasis is placed on human data and regulatory pathways
      involved in CYP regulation and lung carcinogenesis. The most exciting new
      research findings concern cross-talk of the CYP-regulating aryl hydrocarbon
      receptor with other transcription factors, such as nuclear factor-erythroid 2
      related factor 2, involved in the regulation of xenobiotic metabolism and
      antioxidant enzymes. This cross-talk between transcription factors may provide
      mechanistic evidence for clinically relevant issues, such as differences in lung
      cancers between men and women and the synergism between tobacco and asbestos as
      lung carcinogens.

PMID- 21097656
TI  - A decade of mycophenolate mofetil for lupus nephritis: is the glass half-empty or
      half-full?

PMID- 21097655
TI  - TNF-alpha-converting enzyme/a disintegrin and metalloprotease-17 mediates
      mechanotransduction in murine tracheal epithelial cells.
AB  - Bronchoconstriction applies compressive stress to airway epithelial cells. We
      show that the application of compressive stress to cultured murine tracheal
      epithelial cells elicits the increased phosphorylation of extracellular signal
      regulated kinase (ERK) and Akt through an epidermal growth factor receptor (EGFR)
      dependent process, consistent with previous observations of the
      bronchoconstriction-induced activation of EGFR in both human and murine airways.
      Mechanotransduction requires metalloprotease activity, indicating a pivotal role
      for proteolytic EGF-family ligand shedding. However, cells derived from mice with
      targeted deletions of the EGFR ligands Tgfalpha and Hb-egf showed only modest
      decreases in responses, even when combined with neutralizing antibodies to the
      EGFR ligands epiregulin and amphiregulin, suggesting redundant or compensatory
      roles for individual EGF family members in mechanotransduction. In contrast,
      cells harvested from mice with a conditional deletion of the gene encoding the
      TNF-alpha-converting enzyme (TACE/ADAM17), a sheddase for multiple EGF-family
      proligands, displayed a near-complete attenuation of ERK and Akt phosphorylation
      responses and compressive stress-induced gene regulation. Our data provide strong
      evidence that TACE plays a critical central role in the transduction of
      compressive stress.

PMID- 21097657
TI  - Prevention of autoimmune rheumatic disease: state of the art and future
      perspectives.
AB  - Prevention of disease can in principle be accomplished by identification of
      environmental and/or lifestyle risk and protective factors followed by public
      health measures (such as for smoking and lung cancer), or by modification of the
      individual's reactions to disease-inducing factors (such as in vaccinations
      against microbes). This review discusses both options based on emerging
      understanding of aetiologies in inflammatory rheumatic diseases such as
      rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The major
      current opportunity for public health-based prevention lies in avoiding smoking.
      In RA, recent studies have calculated that, in Sweden (a country characterised by
      a low frequency of smoking), 20% of all RA cases and 33% of all cases of ACPA
      positive RA would not have occurred in a smoke-free society. Smoking is also a
      major risk factor for SLE but no population attribution is yet available. New
      avenues for individualised and biology-based prevention are provided by the
      demonstration that several autoimmune rheumatic diseases are preceded by
      emergence of subclinical autoimmunity followed by laboratory-based signs of
      inflammation and finally overt disease. Examples of this process are provided
      from studies of autoimmunity to citrullinated proteins (in RA), to dsDNA (in SLE
      in general) and to Ro52 epitopes (in the case of neonatal heart block). The
      recognition of this sequence of events provides opportunities to intervene
      specifically and potentially curatively before onset of full-blown disease. Such
      prevention can be accomplished by modification of inciting antigens
      (environment), by modification of immunity (more or less specific
      immunomodulation) or by modification of specific gene functions. In all cases,
      prevention will be different in different subsets of disease and differ at
      different time points of disease development. Thus, the road map towards
      prevention of autoimmune rheumatic diseases includes increased understanding of
      how genes, environment and immunity interact.

PMID- 21097659
TI  - Interaction effect of functional variants of the BDNF and DRD2/ANKK1 gene is
      associated with alexithymia in healthy human subjects.
AB  - OBJECTIVE: To test the hypothesis that the interaction between the brain-derived
      neurotrophic factor (BDNF) and dopamine receptor D(2) (DRD2)/ANKK1 gene
      contributes to individual differences in alexithymia. The personality construct
      of alexithymia refers to difficulties in emotional self-regulation and
      contributes as a risk factor to several mental disorders. Alexithymic individuals
      show an impoverished conscious experience of emotions but an intact autonomic
      emotional response. Persons with high alexithymia scores reportedly show a
      reduced activation of the anterior cingulate cortex (ACC) during the processing
      of emotional stimuli. An interaction between two polymorphisms on the BDNF and
      DRD2/ANKK1 gene has been recently associated with reduced gray matter volume in
      the ACC and higher trait anxiety. METHODS: We conducted a genetic association
      study. A total of 664 healthy participants completed the Toronto Alexithymia
      Scale questionnaire and were genotyped for the BDNF Val66Met (rs6265) and the
      DRD2/ANKK1 Taq IA (rs1800497) polymorphisms. RESULTS: Carriers of at least one
      BDNF 66Met and one DRD2/ANKK1 A1 allele showed the highest scores in the total
      Toronto Alexithymia Scale and in the subscale "Difficulties Identifying
      Feelings." CONCLUSION: In line with recent studies investigating the role of BDNF
      Val66Met and DRD2/ANKK1 Taq IA polymorphisms on anxiety and gray matter volume in
      the ACC, our findings provide the first evidence for a genetic contribution to
      alexithymia.

PMID- 21097658
TI  - Sleep variability, health-related practices, and inflammatory markers in a
      community dwelling sample of older adults.
AB  - OBJECTIVE: To explore relationships between wake- and sleep-related health
      behaviors and circulating concentrations of inflammatory markers (interleukin
      [IL]-6 and tumor necrosis factor [TNF]-alpha) in a cohort of community dwelling
      older adults. Low-grade chronic inflammation is an important risk factor for age
      related morbidity. Health behaviors, including average aggregate measures of
      sleep, have been linked to increased inflammation in older adults. Variability in
      sleep timing may also be associated with increased inflammation. METHOD:
      Participants were community dwelling older adults >= 60 years (n = 222: 39
      bereaved, 55 caregivers, 52 with insomnia, and 76 good sleepers). Mean values and
      intraindividual variability in sleep, as well as caffeine and alcohol use,
      exercise, and daytime napping, were assessed by sleep diaries. Blood samples were
      obtained in the morning. RESULTS: Several interactions were noted between sleep
      behaviors, inflammatory markers, and participant group. Greater variability in
      wake time and time in bed was associated with higher IL-6 among good sleepers
      relative to caregivers and older adults with insomnia. Good sleepers who consumed
      moderate amounts of alcohol had the lowest concentrations of IL-6 compared with
      the other three groups who consumed alcohol. Insomnia subjects, but not good
      sleepers, showed increased concentrations of IL-6 associated with caffeine use.
      Caregivers showed increased concentrations of TNF-alpha with alcohol use relative
      to good sleepers. Greater variability in bedtime, later wake times, and longer
      time in bed was associated with higher TNF-alpha regardless of group.
      CONCLUSIONS: Moderation and regularity in the practice of certain health
      behaviors, including sleep practices, were associated with lower plasma levels of
      inflammatory markers in older adults. Life circumstances and specific sleep
      disorders may modify these associations.

PMID- 21097660
TI  - Modeling social influences on human health.
AB  - Social interactions have long-term physiological, psychological, and behavioral
      consequences. Social isolation is a well-recognized but little understood risk
      factor and prognostic marker of disease; it can have profoundly detrimental
      effects on both mental and physical well-being, particularly during states of
      compromised health. In contrast, the health benefits associated with social
      support (both reduced risk and improved recovery) are evident in a variety of
      illnesses and injury states; however, the mechanisms by which social interactions
      influence disease pathogenesis remain largely unidentified. The substantial
      health impact of the psychosocial environment can occur independently of
      traditional disease risk factors and is not accounted for solely by peer
      encouraged development of health behaviors. Instead, social interactions are
      capable of altering shared pathophysiological mechanisms of multiple disease
      states in distinct measurable ways. Converging evidence from animal models of
      injury and disease recapitulates the physiological benefits of affiliative social
      interactions and establishes several endogenous mechanisms (inflammatory signals,
      glucocorticoids, and oxytocin) by which social interactions influence health
      outcomes. Taken together, both clinical and animal research are undoubtedly
      necessary to develop a complete mechanistic understanding of social influences on
      health.

PMID- 21097661
TI  - 24-hour autonomic dysfunction and depressive behaviors in an animal model of
      social isolation: implications for the study of depression and cardiovascular
      disease.
AB  - OBJECTIVE: To investigate the hypothesis that long-term social isolation in an
      animal model would produce depression-relevant behaviors and disruptions in the
      24-hour autonomic and activity parameters, and to further demonstrate the utility
      and validity of an animal model for the study of social environment, behavior,
      and autonomic function. Converging evidence from both experimental and
      epidemiological studies indicates that there is a bidirectional association
      between depression and cardiovascular disease; however, the precise
      neurobiological mechanisms underlying this relationship are not well understood.
      Disruptions in the social environment may influence this relationship. METHODS:
      Depression-relevant behaviors and ambulatory electrocardiographic and activity
      data were measured in 12 adult, socially monogamous prairie voles (rodents)
      during a period of chronic social isolation or social pairing (control
      conditions). RESULTS: Prairie voles exposed to 4 weeks of social isolation versus
      control conditions (social pairing) exhibited anhedonia, increased 24-hour heart
      rate, reduced 24-hour heart rate variability, and predictable correlations
      between the behavioral measure (anhedonia) and the autonomic measures.
      CONCLUSIONS: Social isolation is associated with depressive behaviors, 24-hour
      autonomic dysfunction, and predictable interrelationships between these variables
      in prairie voles but does not seem to be associated with rhythmicity changes in
      activity level or autonomic function. These findings have implications for
      understanding the role of the social environment in mediating the association of
      mood and cardiovascular disorders in humans.

PMID- 21097662
TI  - Spatial and temporal heterogeneities are localized to the right ventricular
      outflow tract in a heterozygotic Scn5a mouse model.
AB  - Ventricular tachycardia (VT) in Brugada Syndrome patients often originates in the
      right ventricular outflow tract (RVOT). We explore the physiological basis for
      this observation using murine whole heart preparations. Ventricular bipolar
      electrograms and monophasic action potentials were recorded from seven epicardial
      positions in Langendorff-perfused wild-type and Scn5a+/- hearts. VT first
      appeared in the RVOT, implicating it as an arrhythmogenic focus in Scn5a+/-
      hearts. RVOTs showed the greatest heterogeneity in refractory periods, response
      latencies, and action potential durations, and the most fractionated
      electrograms. However, incidences of concordant alternans in dynamic pacing
      protocol recordings were unaffected by the Scn5a+/- mutation or pharmacological
      intervention. Conversely, particularly at the RVOT, Scn5a+/- hearts showed
      earlier and more frequent transitions into discordant alternans. This was
      accentuated by flecainide, but reduced by quinidine, in parallel with their
      respective pro- and anti-arrhythmic effects. Discordant alternans preceded all
      episodes of VT. The RVOT of Scn5a+/- hearts also showed steeper restitution
      curves, with the diastolic interval at which the gradient equaled one strongly
      correlating with the diastolic interval at which discordant alternans commenced.
      We attribute the arrhythmic tendency within the RVOT to the greater spatial
      heterogeneities in baseline electrophysiological properties. These, in turn, give
      rise to a tendency to drive concordant alternans phenomena into an arrhythmogenic
      discordant alternans. Our findings may contribute to future work investigating
      possible pharmacological treatments for a disease in which the current mainstay
      of treatment is implantable cardioverter defibrillator implantation.

PMID- 21097663
TI  - Slow and incomplete sympathetic reinnervation of rat tail artery restores the
      amplitude of nerve-evoked contractions provided a perivascular plexus is present.
AB  - We have investigated the recovery of sympathetic control following reinnervation
      of denervated rat tail arteries by relating the reappearance of noradrenergic
      terminals to the amplitude of nerve-evoked contractions of isometrically mounted
      artery segments in vitro. We have also assessed reactivity to vasoconstrictor
      agonists. Freezing the collector nerves near the base of the tail in adult rats
      denervated the artery from ~40 mm along the tail. Restoration of the perivascular
      plexus declined along the length of the tail, remaining incomplete for >6 mo.
      After 4 mo, nerve-evoked contractions were prolonged but of comparable amplitude
      to control at ~60 mm along the tail; they were smaller at ~110 mm. At ~60 mm,
      facilitation of contractions to short trains of stimuli by the norepinephrine
      transporter blocker, desmethylimipramine, and by the alpha2-adrenoceptor
      antagonist, idazoxan, was reduced in reinnervated arteries. Blockade of nerve
      evoked contractions by the alpha1-adrenoceptor antagonist, prazosin, was less and
      by idazoxan greater than control after 8 wk but similar to control after 16 wk.
      Sensitivity of reinnervated arteries to the alpha1-adrenoceptor agonist,
      phenylephrine, was raised in the absence but not in the presence of
      desmethylimipramine. Sensitivity to the alpha2-adrenoceptor agonist, clonidine,
      was maintained in 16-wk reinnervated arteries when it had declined in controls.
      Thus regenerating sympathetic axons have a limited capacity to reinnervate the
      rat tail artery, but nerve-evoked contractions match control once a relatively
      sparse perivascular plexus is reestablished. Functional recovery involves
      prolongation of contractions and deficits in both clearance of released
      norepinephrine and autoinhibition of norepinephrine release.

PMID- 21097664
TI  - Proteolytic cleavage of covalently linked cell wall proteins by Candida albicans
      Sap9 and Sap10.
AB  - The cell wall of the human-pathogenic fungus Candida albicans is a robust but
      also dynamic structure which mediates adaptation to changing environmental
      conditions during infection. Sap9 and Sap10 are cell surface-associated proteases
      which function in C. albicans cell wall integrity and interaction with human
      epithelial cells and neutrophils. In this study, we have analyzed the enzymatic
      properties of Sap9 and Sap10 and investigated whether these proteases cleave
      proteins on the fungal cell surface. We show that Sap9 and Sap10, in contrast to
      other aspartic proteases, exhibit a near-neutral pH optimum of proteolytic
      activity and prefer the processing of peptides containing basic or dibasic
      residues. However, both proteases also cleaved at nonbasic sites, and not all
      tested peptides with dibasic residues were processed. By digesting isolated cell
      walls with Sap9 or Sap10, we identified the covalently linked cell wall proteins
      (CWPs) Cht2, Ywp1, Als2, Rhd3, Rbt5, Ecm33, and Pga4 as in vitro protease
      substrates. Proteolytic cleavage of the chitinase Cht2 and the glucan-cross
      linking protein Pir1 by Sap9 was verified using hemagglutinin (HA) epitope-tagged
      versions of both proteins. Deletion of the SAP9 and SAP10 genes resulted in a
      reduction of cell-associated chitinase activity similar to that upon deletion of
      CHT2, suggesting a direct influence of Sap9 and Sap10 on Cht2 function. In
      contrast, cell surface changes elicited by SAP9 and SAP10 deletion had no major
      impact on the phagocytosis and killing of C. albicans by human macrophages. We
      propose that Sap9 and Sap10 influence distinct cell wall functions by proteolytic
      cleavage of covalently linked cell wall proteins.

PMID- 21097665
TI  - Hph1 and Hph2 are novel components of the Sec63/Sec62 posttranslational
      translocation complex that aid in vacuolar proton ATPase biogenesis.
AB  - Hph1 and Hph2 are homologous integral endoplasmic reticulum (ER) membrane
      proteins required for Saccharomyces cerevisiae survival under environmental
      stress conditions. To investigate the molecular functions of Hph1 and Hph2, we
      carried out a split-ubiquitin-membrane-based yeast two-hybrid screen and
      identified their interactions with Sec71, a subunit of the Sec63/Sec62 complex,
      which mediates posttranslational translocation of proteins into the ER. Hph1 and
      Hph2 likely function in posttranslational translocation, as they interact with
      other Sec63/Sec62 complex subunits, i.e., Sec72, Sec62, and Sec63. hph1Delta
      hph2Delta cells display reduced vacuole acidification; increased instability of
      Vph1, a subunit of vacuolar proton ATPase (V-ATPase); and growth defects similar
      to those of mutants lacking V-ATPase activity. sec71Delta cells exhibit similar
      phenotypes, indicating that Hph1/Hph2 and the Sec63/Sec62 complex function during
      V-ATPase biogenesis. Hph1/Hph2 and the Sec63/Sec62 complex may act together in
      this process, as vacuolar acidification and Vph1 stability are compromised to the
      same extent in hph1Delta hph2Delta and hph1Delta hph2Delta sec71Delta cells. In
      contrast, loss of Pkr1, an ER protein that promotes posttranslocation assembly of
      Vph1 with V-ATPase subunits, further exacerbates hph1Delta hph2Delta phenotypes,
      suggesting that Hph1 and Hph2 function independently of Pkr1-mediated V-ATPase
      assembly. We propose that Hph1 and Hph2 aid Sec63/Sec62-mediated translocation of
      specific proteins, including factors that promote efficient biogenesis of V
      ATPase, to support yeast cell survival during environmental stress.

PMID- 21097667
TI  - The Rag4 glucose sensor is involved in the hypoxic induction of KlPDC1 gene
      expression in the yeast Kluyveromyces lactis.
AB  - Kluyveromyces lactis is a yeast which cannot grow under strict anaerobiosis. To
      date, no factors responsible for oxygen sensing and oxygen-dependent regulation
      of metabolism have been identified. In this paper we present the identification
      of the glucose sensor Rag4 as a factor essential for oxygen-dependent regulation
      of the fermentative pathway.

PMID- 21097666
TI  - Loss of heterozygosity at an unlinked genomic locus is responsible for the
      phenotype of a Candida albicans sap4Delta sap5Delta sap6Delta mutant.
AB  - The diploid genome of the pathogenic yeast Candida albicans exhibits a high
      degree of heterozygosity. Genomic alterations that result in a loss of
      heterozygosity at specific loci may affect phenotypes and confer a selective
      advantage under certain conditions. Such genomic rearrangements can also occur
      during the construction of C. albicans mutants and remain undetected. The SAP2
      gene on chromosome R encodes a secreted aspartic protease that is induced and
      required for growth of C. albicans when proteins are the only available nitrogen
      source. In strain SC5314, the two SAP2 alleles are functionally divergent because
      of differences in their regulation. Basal expression of the SAP2-2 allele, but
      not the SAP2-1 allele, provides the proteolytic degradation products that serve
      as inducers for full SAP2 induction. A triple mutant lacking the SAP4, SAP5, and
      SAP6 genes, which are located on chromosome 6, has previously been reported to
      have a growth defect on proteins, suggesting that one of the encoded proteases is
      required for SAP2 expression. Here we show that this sap4Delta sap5Delta
      sap6Delta mutant has become homozygous for chromosome R and lost the SAP2-2
      allele. Replacement of one of the SAP2-1 copies in this strain by SAP2-2 and its
      regulatory region restored the ability of the sap4Delta sap5Delta sap6Delta
      mutant to utilize proteins as the sole nitrogen source. This is an illustrative
      example of how loss of heterozygosity at a different genomic locus can cause the
      mutant phenotype attributed to targeted deletion of a specific gene in C.
      albicans.

PMID- 21097668
TI  - Testosterone therapy: treatment of metabolic disturbances in heart failure.
AB  - Heart failure (HF) is a complex progressive multisystem disease state with
      significant morbidity and mortality, which is not solely defined by pathology of
      the cardiovascular system but also is influenced by neurohormonal regulatory
      adjustments, peripheral cytokines, as well as hormonal and musculoskeletal
      dysfunction. Recent attention to the catabolic state found in patients with
      chronic heart failure has sparked interest in new potential targets for medical
      therapy. In particular, as many as 26% to 37% of men affected with HF have been
      found to be testosterone deficient. The severity of androgen deficiency has been
      shown to correlate with symptoms, functional class, and prognosis in patients
      with heart failure. Testosterone supplementation has been an accepted therapy in
      hypogonadal men with fatigue, muscle wasting, and sexual dysfunction for some
      time. Patients with severe HF show a similar constellation of symptoms and
      hypothetically would benefit from androgen replacement. Recent clinical studies
      have confirmed that functional, biochemical, and cardiopulmonary status in
      patients with HF have significant improvements when treated with testosterone
      supplementation. Symptomatic improvements may be obtainable in hypogonadal
      patients with HF who receive supplemental testosterone. This review seeks to
      outline the cardiovascular and peripheral effects of testosterone supplementation
      in patients with chronic HF.

PMID- 21097669
TI  - Clinical applications of bivalirudin in the cardiac catheterization laboratory.
AB  - Heparin has been used in the catheterization laboratory to prevent ischemic
      complications of percutaneous coronary intervention (PCI). Bivalirudin, a direct
      thrombin inhibitor, is an anticoagulant that has several pharmacologic advantages
      over heparin, and it has been proposed that bivalirudin is superior to heparin in
      its ability to prevent bleeding complications of PCI. As such, there have been a
      variety of large prospective clinical trials comparing bivalirudin and heparin
      over the past 13 years. The results of these trials have prompted the general
      acceptance of bivalirudin as a safe alternative to heparin use during PCI, and
      bivalirudin has been given a class 1 recommendation by the American College of
      Cardiology/American Heart Association (ACC/AHA) guidelines for a variety of
      clinical indications. This article will review the data supporting the use of
      bivalirudin in the cardiac catheterization laboratory and describe several
      advantages of bivalirudin over traditional heparin use. We also include a
      discussion of the use of bivalirudin in conjunction with other medications that
      are frequently used in the catheterization laboratory. We end with an analysis of
      the economic differences between bivalirudin and heparin and the impact that
      financial factors may have on the choice of anticoagulant.

PMID- 21097670
TI  - Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during
      transendothelial migration.
AB  - Epithin/PRSS14, a type II transmembrane serine protease, is involved in normal
      epithelial development and tumor progression. Here we report, as an interacting
      substrate of epithin, a receptor tyrosine kinase Tie2 that is well known for
      important roles in the vessel stability. Epithin interacts with and degrades the
      Tie2 extracellular portion that contains the ligand-binding domain. Epithin is
      located in the neighbor of Tie2-expressing vessels in normal tissue. Furthermore,
      epithin can cleave and degrade Tie2 not only in the same cell but also from
      neighboring cells nearby, resulting in the degradation of the Tie2 ectodomain.
      The remaining Tie2 fragment was highly phosphorylated and was able to recruit a
      downstream effector, phosphatidylinositol 3-kinase. Knocking down epithin
      expression using short hairpin RNA in thymoma cell severely impaired the
      migration through endothelial cells that show the actin rearrangement during the
      process. The diminution of epithin protein expression in 4T1 breast cancer cells
      caused the significant decrease in the number of transendothelial migrating cells
      in vitro as well as in those of metastasizing tumor nodules in vivo, Therefore,
      we propose that epithin, which regulates endothelial Tie2 functions, plays a
      critical role in the fine tuning of transendothelial migration for normal and
      cancer cells.

PMID- 21097671
TI  - T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to
      immunosuppressive therapy.
AB  - Clinical observations and laboratory evidence link bone marrow failure in
      myelodysplastic syndrome (MDS) to a T cell-mediated immune process that is
      responsive to immunosuppressive treatment (IST) in some patients. Previously, we
      showed that trisomy 8 MDS patients had clonally expanded CD8(+) T-cell
      populations that recognized aneuploid hematopoietic progenitor cells (HPC).
      Furthermore, microarray analyses showed that Wilms tumor 1 (WT1) gene was
      overexpressed by trisomy 8 hematopoietic progenitor (CD34(+)) cells compared with
      CD34(+) cells from healthy donors. Here, we show that WT1 mRNA expression is up
      regulated in the bone marrow mononuclear cells of MDS patients with trisomy 8
      relative to healthy controls and non-trisomy 8 MDS; WT1 protein levels were also
      significantly elevated. In addition, using a combination of physical and
      functional assays to detect the presence and reactivity of specific T cells,
      respectively, we demonstrate that IST-responsive MDS patients exhibit significant
      CD4(+) and CD8(+) T-cell responses directed against WT1. Finally, WT1-specific
      CD8(+) T cells were present within expanded T-cell receptor Vbeta subfamilies and
      inhibited hematopoiesis when added to autologous patient bone marrow cells in
      culture. Thus, our results suggest that WT1 is one of the antigens that triggers
      T cell-mediated myelosuppression in MDS.

PMID- 21097672
TI  - Osteoclast-gene expression profiling reveals osteoclast-derived CCR2 chemokines
      promoting myeloma cell migration.
AB  - Multiple myeloma is characterized by the clonal expansion of malignant plasma
      cells (multiple myeloma cells [MMCs]), in the bone marrow. Osteolytic bone
      lesions are detected in 80% of patients because of increased osteoclastic bone
      resorption and reduced osteoblastic bone formation. MMCs are found closely
      associated with sites of increased bone resorption. Osteoclasts strongly support
      MMC survival in vitro. To further elucidate the mechanisms involved in
      osteoclast/MMC interaction, we have identified 552 genes overexpressed in
      osteoclasts compared with other bone marrow cell subpopulations. Osteoclasts
      express specifically genes coding for 4 CCR2-targeting chemokines and genes
      coding for MMC growth factors. An anti-CCR2 monoclonal antibody blocked
      osteoclast chemoattractant activity for MMC, and CCR2 chemokines are also MMC
      growth factors, promoting mitogen-activated protein kinase activation in MMC. An
      anti-insulin growth factor-1 receptor monoclonal antibody completely blocked the
      osteoclast-induced survival of MMC suppressing both osteoclast and MMC survival.
      Specific a proliferation-inducing ligand or IL-6 inhibitors partially blocked
      osteoclast-induced MMC survival. These data may explain why newly diagnosed
      patients whose MMC express high levels of CCR2 present numerous bone lesions.
      This study displays additional mechanisms involved in osteoclast/MMC interaction
      and suggests using CCR2 and/or insulin growth factor-1 targeting strategies to
      block this interaction and prevent drug resistance.

PMID- 21097673
TI  - Towards individualized follow-up in adult acute myeloid leukemia in remission.
AB  - An increasing body of data has demonstrated that the traditional concept of
      morphologic complete remission in acute myeloid leukemia, in which less than 5%
      myeloblasts is regarded as a sufficient response criterion, is not biologically
      sound. Fortunately, the quantitative reverse-transcribed polymerase chain
      reaction (RT-PCR) method seems to be a promising alternative because of its high
      degree of preclinical standardization and extreme sensitivity on the background
      of an accurate day-to-day estimate of sample quality. Widespread implementation
      of this has, however, to some extent been hampered by the lack of knowledge of
      how and when to measure minimal residual disease levels and, even more
      importantly, how to react preemptively on a molecular relapse defined by a PCR
      reversal. Thus, only few prospective studies have been published to date to
      clinically validate this assay. Here, we discuss outstanding issues in the
      clinical implementation of RT-PCR for fusion transcripts, mutated and
      overexpressed genes in acute myeloid leukemia patients in complete remission, and
      propose a set of guidelines, which can be used when designing prospective trials
      aimed at validating the use of RT-PCR as well as for following these patients
      based on mathematical models for disease recurrence recently developed in our
      laboratory.

PMID- 21097674
TI  - Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host
      disease.
AB  - Investigation of the effects of rituximab (anti-CD20) on B-cell-activating factor
      of the tumor necrosis factor family (BAFF) and B cells would better define the
      significance of B-cell homeostasis in chronic graft-versus-host disease (cGVHD)
      pathophysiology. We studied 20 cGVHD patients at a median of 25 months after
      rituximab treatment when most patients had recovered total B-cell numbers. A
      total of 55% of patients had stable/improved cGVHD, and total B-cell numbers in
      these patients were significantly higher compared with rituximab-unresponsive
      patients. Although total B-cell number did not differ significantly between cGVHD
      groups before rituximab, there was a proportional increase in B-cell precursors
      in patients who later had stable/improved cGVHD. After rituximab, BAFF levels
      increased in all patients. Coincident with B-cell recovery in the stable/improved
      group, BAFF/B-cell ratios and CD27(+) B-cell frequencies decreased significantly.
      The peripheral B-cell pool in stable/improved cGVHD patients was largely composed
      of naive IgD(+) B cells. By contrast, rituximab-unresponsive cGVHD patients had
      persistent elevation of BAFF and a predominance of circulating B cells possessing
      an activated BAFF-R(Lo)CD20(Lo) cell surface phenotype. Thus, naive B-cell
      reconstitution and decreased BAFF/B-cell ratios were associated with clinical
      response after rituximab in cGVHD. Our findings begin to delineate B-cell
      homeostatic mechanisms important for human immune tolerance.

PMID- 21097675
TI  - Lunatic Fringe prolongs Delta/Notch-induced self-renewal of committed alphabeta T
      cell progenitors.
AB  - Lunatic Fringe (Lfng) enhances Notch1 activation by Delta-like 4 (DL4) to promote
      Notch1-dependent T-lineage commitment of thymus-seeding progenitors.
      Subsequently, Notch1 and T-cell receptor-beta (TCRbeta)-containing pre-TCR
      complexes signal CD4/CD8 double-negative 3 (DN3) committed T-cell progenitors to
      survive, proliferate, and differentiate into CD4/CD8 double-positive (DP)
      alphabeta T-cell precursors. Few DP thymocytes develop without Notch1 or pre-TCR
      signals, whereas ectopic Notch1 activation causes T-cell leukemia. However,
      mechanisms of a Notch-pre-TCR collaboration during this "beta-selection" process
      are poorly understood. We genetically manipulated Lfng to attenuate or enhance
      Notch1 activation in DN3 thymocytes without inducing leukemogenesis. We show that
      Lfng temporally sustains DL-induced Notch1 signaling to prolong proliferative
      self-renewal of pre-DP thymocytes. Pre-TCR signaling greatly augmented Notch
      trophic functions to promote robust proliferation of pre-DP progenitors. In
      contrast, in the absence of DL/Notch signaling, pre-TCR-expressing progenitors
      rapidly atrophied and differentiated into DP thymocytes. Thus, Lfng prolongs
      Notch1 signaling to promote self-renewal more than differentiation during the
      early stages of beta-selection. Our data provide novel insights into the Notch
      pre-TCR collaboration, and suggest that decreasing Lfng expression during the DN3
      DP transition minimizes the potent leukemogenic potential of Notch1 signaling.

PMID- 21097676
TI  - Inverse log-linear relationship between thyroid-stimulating hormone and free
      thyroxine measured by direct analog immunoassay and tandem mass spectrometry.
AB  - BACKGROUND: Accurate measurement of free thyroxine (FT(4)) is important for
      diagnosing and managing thyroid disorders. Most laboratories measure FT(4) by
      direct analogue immunoassay methods. The validity of these methods have recently
      been questioned. The inverse log-linear relationship between FT(4) and thyroid
      stimulating hormone (TSH) is well described and provides a physiological
      rationale on which to base an evaluation of FT(4) assays. METHODS: The study
      included 109 participants for whom FT(4) measurement was requested by their
      clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH
      and albumin results. FT(4) and TSH were measured by use of the Siemens Immulite
      immunoassay (IA). FT(4) was also measured by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) (MS-FT(4)). RESULTS: The inverse log-linear correlation
      coefficient between TSH and FT(4) was significantly better (P < 0.0001) for MS
      FT(4) (0.84, 95% CI, 0.77-0.88) than for IA-FT(4) (0.45, 95% CI, 0.29-0.59). IA
      FT(4) showed a significant correlation with albumin (Spearman correlation
      coefficient 0.45, 95% CI, 0.29-0.5, P < 0.0001) and thyroxine-binding globulin
      (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05-0.41, P = 0.02). In
      contrast, FT(4) measurement by LC-MS/MS did not show a significant correlation
      with albumin or TBG. CONCLUSIONS: The inverse log-linear relationship between
      FT(4) and TSH was significantly better for FT(4) measured by LC-MS/MS than by IA.
      The MS-FT(4) method therefore provides FT(4) results that agree clinically with
      those obtained for TSH. Additionally, the significant correlation between IA
      FT(4) with albumin and TBG suggests that this FT(4) method depends on binding
      protein concentrations and consequently does not accurately reflect FT(4).

PMID- 21097677
TI  - Commutability limitations influence quality control results with different
      reagent lots.
AB  - BACKGROUND: Good laboratory practice includes verifying that each new lot of
      reagents is suitable for use before it is put into service. Noncommutability of
      quality control (QC) samples with clinical patient samples may preclude their use
      to verify consistency of results for patient samples between different reagent
      lots. METHODS: Patient sample results and QC data were obtained from reagent lot
      change verification records for 18 QC materials, 661 reagent lot changes, 1483
      reagent lot change-QC events, 82 analytes, and 7 instrument platforms. The
      significance of between-lot differences in the results for QC samples compared
      with those for patient samples was assessed by a modified 2-sample t test
      adjusted for heterogeneity of QC and patient sample measurement variances.
      RESULTS: Overall, 40.9% of reagent lot change-QC events had a significant
      difference (P < 0.05) between results for QC samples compared with results for
      patient samples between 2 reagent lots. For QC results with differences <1.0 SD
      interval (83.1% of total), 37.7% were significantly different from the changes
      observed for patient samples. For QC results with differences >=1.0 SD interval
      (16.9% of total), 57.0% were significantly different from those for patient
      samples. CONCLUSIONS: Occurrence of noncommutable results for QC materials was
      frequent enough that the QC results could not be used to verify consistency of
      results for patient samples when changing lots of reagents.

PMID- 21097678
TI  - NSAID inhibition of prostate cancer cell migration is mediated by Nag-1 Induction
      via the p38 MAPK-p75(NTR) pathway.
AB  - The nonsteroidal anti-inflammatory drugs (NSAID) R-flurbiprofen and ibuprofen
      have been shown to induce expression of p75(NTR) (neurotrophin receptor) in
      prostate cancer cell lines. p75(NTR), a tumor necrosis factor receptor
      superfamily member, is a proapoptotic protein that functions as a tumor
      suppressor in the human prostate. Expression of p75(NTR) is lost as prostate
      cancer progresses and is minimal in several metastatic prostate cancer cell
      lines. NSAIDs induce p75(NTR) through activation of the p38 mitogen-activated
      protein kinase (MAPK) pathway, with a concomitant decrease in cell survival.
      Here, we show that treatment with R-flurbiprofen and ibuprofen induces expression
      of the NSAID-activated gene-1 (Nag-1) protein, a divergent member of the TGF beta
      (TGF-beta) family, in PC-3 cells. Using the selective pharmacologic inhibitor of
      p38 MAPK, SB202190, and p38 MAPK-specific siRNA (small interfering RNA), we show
      that Nag-1 induction following NSAID treatment is mediated by the p38 MAPK
      pathway. p75(NTR)-specific siRNA pretreatment shows that Nag-1 induction by
      NSAIDs is downstream of p75(NTR) induction. Decreased survival of NSAID-treated
      cells is rescued by p75(NTR)-specific siRNA but not by Nag-1 siRNA. Transwell
      chamber and in vitro wound healing assays demonstrate decreased cell migration
      upon NSAID treatment. Pretreatment of PC-3 cells with p75(NTR) and Nag-1-specific
      siRNA shows that NSAID inhibition of cell migration is mediated by Nag-1 and
      p75(NTR). These results demonstrate a role for Nag-1 in NSAID inhibition of cell
      migration, but not survival.

PMID- 21097679
TI  - Quality and production trait genetics of farmed European whitefish, Coregonus
      lavaretus.
AB  - We present here phenotypic and genetic parameters for the major quality and
      production traits of farmed European whitefish. A total of 70 families were
      produced by mating each of 45 sires to an average of 1.6 dams and each of the 52
      dams to an average of 1.3 sires. A total of 2,100 individuals were recorded for
      survival, and 507 individuals for growth and quality-related traits. The 4 major
      results were as follows: first, all traits exhibited nonzero heritabilities
      except for fillet gaping and fillet protein%. The heritabilities for the
      production traits were harvest weight (0.42 +/- 0.10), gutted weight (0.40 +/-
      0.10), fillet weight (0.36 +/- 0.09), maturity score (0.27 +/- 0.11, on liability
      scale), survival (0.19 +/- 0.05, on liability scale), carcass% (0.14 +/- 0.07),
      and fillet% (0.11 +/- 0.06). The heritabilities for the quality traits were
      condition factor (0.49 +/- 0.10), fillet lipid% (0.37 +/- 0.10), muscle texture
      (0.30 +/- 0.09), Distell lipid reading (0.26 +/- 0.09), fillet lightness (0.16 +/
      0.07), fillet gaping (0.04 +/- 0.06), and fillet protein% (0.04 +/- 0.06).
      Second, the quality traits that were significantly genetically correlated with
      each other were all related to lipid deposition. Increasing fillet lipid% (an
      undesired change in whitefish) was genetically related to desired lighter fillet
      color [genetic correlation (r(G)) = 0.70 +/- 0.22] and to undesired greater
      condition factor (0.39 +/- 0.17). None of the other genetic correlations between
      condition factor, fillet lipid%, muscle texture, fillet lightness, fillet gaping,
      and fillet protein% were significant. Third, BW and gutted weight were
      genetically related to the quality traits that were genetically related to lipid
      deposition. Increasing harvest weight was genetically related to high fillet
      lipid% (r(G) = 0.59 +/- 0.14), lighter fillet color (0.61 +/- 0.25), and to
      greater condition factor (0.60 +/- 0.12). All other genetic correlations of
      harvest weights with the quality traits were nonsignificant, indicating that
      rapid growth was not genetically related to gaping and softer flesh. Fourth, none
      of the genetic correlations of carcass%, fillet%, maturity, and survival with the
      quality traits were significant, implying weak genetic integration between the
      traits. Yet, marginally significant genetic correlations were found for fillet
      lipid% with maturity score (r(G) = -0.46 +/- 0.24) and survival (0.36 +/- 0.19).
      These results provide the genetic basis for assessing the potential to improve
      product quality via selective breeding.

PMID- 21097680
TI  - Modifying growth curve parameters by multitrait genomic selection.
AB  - The use of genomic selection for changing the growth curve shape of animals,
      acting simultaneously on the 3 parameters of a Gompertz growth curve, was studied
      using computer simulation. Results showed that genomic selection modified the
      growth curve. Responses to all selection criteria were accompanied with a
      correlated response in mature weight due to the high genetic correlations between
      mature weight and the 2 rate parameters. Responses to selection were affected by
      the loss of accuracy over generations of genomic selection due to the loss of
      gametic disequilibrium between SNP and genes determining the parameters. In
      conclusion, genomic selection can be used for changing growth curve parameters.
      However, changing the whole curve (birth weight, adult BW, and curve shape) is
      not easy due to the correlation between all BW along the growth of the animal.
      Applying genomic selection will require a constant reevaluation of the
      associations between SNP and genes determining the curve parameters.

PMID- 21097681
TI  - Phosphorus digestibility and energy concentration of enzyme-treated and
      conventional soybean meal fed to weanling pigs.
AB  - Two experiments were conducted to determine the apparent total tract
      digestibility (ATTD) of P and the concentration of DE and ME in enzyme-treated
      soybean meal (SBM) and in conventional soybean meal (SBM-CV). Phosphorus
      digestibility in 2 enzyme-treated SBM (HP-310 and HP-340) and in SBM-CV was
      measured using 36 barrows (initial BW: 21.9 +/- 1.1 kg) that were housed in
      metabolism cages and randomly allotted to 6 diets with 6 replicates per diet.
      During production, HP-310 had been treated with an enzyme mixture containing no
      phytase, whereas HP-340 was treated with an enzyme mixture that contained
      exogenous phytase. Three diets containing HP-310, HP-340, or SBM-CV as the sole
      source of P were formulated. Three additional diets also contained HP-310, HP
      340, and SBM-CV, but each of these diets was fortified with 500 units of
      microbial phytase. The ATTD of P in HP-310 and SBM-CV increased (P < 0.05) as
      phytase was included in the diet (from 59.8 to 77.7% for HP-310 and from 65.5 to
      79.5% for SBM-CV), but the ATTD of P in HP-340 without and with phytase was not
      different (P > 0.05; 83.8 and 87.7%, respectively). There were no differences (P
      > 0.05) in the ATTD of P between HP-310 and SBM-CV, but the ATTD of P in HP-340
      was greater (P < 0.05) than in the other 2 meals. The DE and ME in corn, 2
      sources of enzyme-treated SBM (HP-200 and HP-310), and in SBM-CV were measured in
      the second experiment using 28 barrows housed in metabolism cages (initial BW:
      16.8 +/- 2.5 kg of BW). The process used to produce HP-200 is similar to that
      used to produce HP-310 except that HP-200 is exposed to the enzymes for a shorter
      period of time than HP-310. A corn-diet consisting of 96.45% corn and vitamins
      and minerals was formulated. Three additional diets were formulated by mixing
      corn and each source of SBM with vitamins and minerals. Pigs were randomly
      allotted to the 4 diets with 7 replicate pigs per diet, and urine and feces were
      collected quantitatively during the last 5 d of a 14-d feeding period. The
      concentration of DE in HP-200, HP-310, and SBM-CV was 4,333, 4,316, and 4,347
      kcal/kg of DM, respectively. These values were not different (P > 0.05), but they
      were greater (P < 0.05) than the DE in corn (3,891 kcal/kg of DM). The
      concentration of ME was 3,780, 3,926, 3,914, and 3,980 kcal/kg of DM in corn, HP
      200, HP-310, and SBM-CV, respectively. These values were not different (P >
      0.05). It is concluded that enzyme treatment of SBM does not influence the
      digestibility of P or the concentration of DE and ME in the meals.

PMID- 21097682
TI  - Electrostatic spraying of antioxidants on the oxidative quality of ground beef.
AB  - To prevent oxidative quality changes, a few selected antioxidants, ascorbic acid,
      or an ascorbic acid plus alpha-tocopherol combination were electrostatically
      sprayed on the surface of ground beef patties. Color, metmyoglobin, oxidation
      reduction potential, lipid oxidation, and volatiles of the samples were
      determined during the 8 d of aerobic storage. Spraying of ascorbic acid at 500
      mg/kg was the most effective in controlling discoloration of ground beef.
      Spraying of ascorbic acid at 500 mg/kg was also effective in reducing 2
      thiobarbituric acid-reactive substances and volatile aldehydes such as hexanal
      and heptanal related to lipid oxidation. Spraying of phenolic antioxidants such
      as tocopherol, sesamol, or rosemary oleoresin showed significant (P < 0.05)
      antioxidant effects, but had no effects (P < 0.05) in stabilizing the color of
      ground beef. Sesamol at 100 mg/kg showed the most potent antioxidant activities
      among the antioxidants, and its antioxidant effect was as strong as that of 500
      mg/kg of ascorbic acid. It was concluded that electrostatic spray of ascorbic
      acid on the surface of ground beef at 500 mg/kg was an efficient and economical
      way to prevent both lipid oxidation and color changes in ground beef.

PMID- 21097683
TI  - Nutrient and energy retention in weaned Iberian piglets fed diets with different
      protein concentrations.
AB  - Fifty-eight purebred castrated male Iberian (IB) piglets (initial BW 9.9 +/- 0.1
      kg) were used in an experiment to determine the effect of dietary protein content
      (PC) and feeding level (FL) on the rates of BW gain, whole body protein
      deposition (PD), and energy utilization between 10 and 25 kg of BW using the
      serial slaughter method. Treatments followed a 4 * 2 factorial arrangement with 4
      PC (201, 176, 149, and 123 g of CP/kg of DM) and 2 FL (0.95 and 0.70 * ad
      libitum) and 6 or 7 piglets per combination of treatments. All diets were
      formulated to have an optimal AA pattern. Six piglets were slaughtered at the
      start of the trial to estimate initial body composition. The experimental pigs
      were individually housed in an environmentally controlled room (27 +/- 2 degrees
      C) until they reached 25 kg of BW, when they were slaughtered and analyzed for
      body composition. Positive linear effects of dietary PC on ADG, G:F, and gain:ME
      intake were observed (P < 0.001). Piglets fed at the highest FL showed greater
      ADG, G:F, and gain:ME intake (P < 0.001). An average increase was estimated to be
      38.0 g of gain/MJ of ME intake. Protein deposition increased linearly from 35.6
      to 50.9 g/d with increasing dietary PC (P < 0.001). A daily increase was
      estimated to be 0.35 g of PD/g of CP intake. Although the maximal genetic
      potential for PD of the IB piglet was not attained, a maximal value of 59.9 g/d
      for whole-body PD was achieved when the diet provided 201 g of CP/kg of DM and
      was fed at 0.95 * ad libitum. Piglets on the highest FL deposited on average 39%
      more body protein (P < 0.001) than restricted piglets. An average value of 4.39 g
      increase in PD/MJ of ME intake was obtained for diets containing 201 and 176 g of
      CP/kg of DM. Maintenance energy requirements and net efficiency of utilization of
      ME for growth, calculated by linear regression of ME intake on body retained
      energy, were 427 kJ/kg of BW(0.75).d(-1) and 0.552, respectively. The
      corresponding partial efficiencies of utilization of ME for protein and fat
      deposition were 0.378 and 0.672, respectively, considerably less than the
      accepted values for conventional pig breeds. Practical diets of the young IB
      piglet should contain at least 201 g of ideal CP/kg of DM.

PMID- 21097684
TI  - Genome-wide mapping and identification of new quantitative trait loci affecting
      meat production, meat quality, and carcass traits within a Duroc purebred
      population.
AB  - Most QTL detection studies in pigs have been carried out in experimental F(2)
      populations. However, segregation of a QTL must be confirmed within a purebred
      population for successful implementation of marker-assisted selection.
      Previously, QTL for meat quality and carcass traits were detected on SSC 7 in a
      Duroc purebred population. The objectives of the present study were to carry out
      a whole-genome QTL analysis (except for SSC 7) for meat production, meat quality,
      and carcass traits and to confirm the presence of segregating QTL in a Duroc
      purebred population. One thousand and four Duroc pigs were studied from base to
      seventh generation; the pigs comprised 1 closed population of a complex
      multigenerational pedigree such that all individuals were related. The pigs were
      evaluated for 6 growth traits, 7 body size traits, 8 carcass traits, 2
      physiological traits, and 11 meat quality traits, and the number of pigs with
      phenotypes ranged from 421 to 953. A total of 119 markers were genotyped and then
      used for QTL analysis. We utilized a pedigree-based, multipoint variance
      components approach to test for linkage between QTL and the phenotypic values
      using a maximum likelihood method; the logarithm of odds score and QTL genotypic
      heritability were estimated. A total of 42 QTL with suggestive linkages and 3 QTL
      with significant linkages for 26 traits were detected. These included selection
      traits such as daily BW gain, backfat thickness, loin eye muscle area, and
      intramuscular fat content as well as correlated traits such as body size and meat
      quality traits. The present study disclosed QTL affecting growth, body size, and
      carcass, physiological, and meat quality traits in a Duroc purebred population.

PMID- 21097685
TI  - Triennial Growth Symposium: a novel pathway for vitamin D-mediated phosphate
      homeostasis: implications for skeleton growth and mineralization.
AB  - Systemic factors that ultimately affect skeletal growth involve
      interrelationships among Ca, parathyroid hormone (PTH), and conversion of 25-OH
      vitamin D(3) to the active hormone, 1alpha,25-(OH)(2)D(3). These
      interrelationships, with a focus on mechanisms that affect Ca homeostasis, are
      referred to as the Ca, PTH, and vitamin D axis. Relatively little research has
      focused on these interrelationships and P homeostasis. In the past decade,
      discovery of a previously unrecognized hormone involved in a pathway for P
      homeostasis offers opportunities to improve P efficiency without compromising
      skeletal growth and animal well-being. The objective of this review was to
      summarize pivotal research discoveries that led to the current understanding of
      the roles of fibroblast growth factor 23 (FGF23) in P homeostasis that are
      independent from the well-described pathways involved with Ca homeostasis. The
      novel pathways are referred to as the FGF23, P, and vitamin D axis. The peptide,
      FGF23, directly affects P homeostasis via action on renal target tissues to
      regulate Na-P transport proteins and renal 25(OH)D(3)-1alpha hydroxylase
      activity. Identification of bone as the primary site for FGF23 production
      ascribes an endocrine gland function to bone. Within 9 h after a single injection
      of recombinant FGF23, mice displayed hypophosphatemia and urinary P wasting. In
      contrast, FGF23 knockout mice displayed hyperphosphatemia and renal P
      conservation. These responses were independent of PTH. Applications of the FGF23,
      P, and vitamin D axis in dietary strategies for animal agriculture need to be
      explored. Development of dietary inputs to balance both Ca and P homeostasis are
      needed to improve skeletal growth and nutrient efficiency.

PMID- 21097686
TI  - New method to combine molecular and pedigree relationships.
AB  - Relationship coefficients are traditionally based on pedigree data. Today, with
      the development of molecular techniques, they are often completely replaced by
      coefficients calculated from molecular data. Examples are relationships from
      microsatellites for biodiversity studies but also genomic relationships from SNP
      as currently used in genomic prediction of breeding values. There are, however,
      many situations in which optimal combination of both sources would be the best
      solutions. Obviously, this is the case for incompletely genotyped populations,
      but also when pedigree information is sparse. Also, markers, even dense ones, do
      not reflect the whole genome and therefore give only an incomplete picture of
      relationships. The main objective of this study was therefore to develop a method
      to calculate a relationship matrix by the combination of molecular and pedigree
      data. It will be useful for all situations where pedigree and molecular data are
      available. In this study, based on simulations of pedigree and marker data, we
      used partial least squares regression and linear regression to combine total
      allelic relationship coefficients calculated for each marker with additive
      relationship coefficients calculated from incomplete pedigree. The results showed
      that the greatest advantage of this method, compared with the one that replaces a
      part of the pedigree-based relationship matrix by a genomic relationship matrix,
      is that adding the partial pedigree data allows for the correction of the
      molecular coefficient for the ungenotyped part of the genome.

PMID- 21097687
TI  - Effects of high-oil corn on feedlot performance, carcass characteristics, fatty
      acid profiles, beef palatability, and retail case life traits of beef top loin
      steaks.
AB  - Our objective was to compare the effects of feeding steam-flaked, high-oil corn
      with normal steam-flaked corn to which yellow grease was added to equalize
      dietary fat on performance and carcass characteristics of finishing beef steers,
      and palatability, retail case life, and fatty acid composition of strip loins.
      Angus steers (n = 120; initial BW = 288 kg) were allotted to dietary treatments
      consisting of 1) normal mill-run, steam-flaked corn plus added fat (NMR) or 2)
      high-oil, steam-flaked corn (HOC) and assigned randomly to pens (12
      pens/treatment with 5 steers/pen). Performance (ADG, DMI, and G:F) was measured
      over time, and cattle were shipped to a commercial abattoir for collection of
      carcass data after 165 d on feed. Carcass data were collected at 48 h postmortem
      on all carcasses, and 2 carcasses from each pen were selected randomly for
      collection of strip loins (IMPS #180A). At 14 d postmortem, 4 steaks (2.54 cm
      thick) were removed for retail display, trained sensory panel analysis, Warner
      Bratzler shear force determination, and fatty acid analysis. Daily BW gain was
      greater (P = 0.03) and G:F was increased 8.4% (P = 0.01) for steers fed NMR
      compared with HOC, but DMI was not affected (P > 0.10) by treatment. No treatment
      differences were observed (P > 0.10) for HCW, 12th-rib fat, KPH, and yield grade.
      Marbling scores were greater (P = 0.01) for NMR than for HOC, and LM area tended
      (P = 0.07) to be greater in NMR than in HOC carcasses. The proportion of
      carcasses grading USDA Choice did not differ (P = 0.77) between treatments, but a
      greater (P = 0.04) proportion of carcasses graded in the upper two-thirds of
      Choice for NMR vs. HOC. Trained sensory panel traits and Warner-Bratzler shear
      force values did not differ between treatments (P > 0.10), and no differences (P
      > 0.10) were detected for purge loss or fatty acid composition. Overall, ADG and
      G:F were less and marbling score was decreased, but there were no differences
      between treatments in beef palatability, retail case life, or concentrations of
      fatty acids in strip loins.

PMID- 21097689
TI  - Nitric oxide-donating acetylsalicylic acid induces apoptosis in chronic
      lymphocytic leukemia cells and shows strong antitumor efficacy in vivo.
AB  - PURPOSE: Nitric oxide-donating acetylsalicylic acid (NO-ASA) has been shown to
      possess an antineoplastic effect in Wnt-/beta-catenin-active cancers. As chronic
      lymphocytic leukemia (CLL) cells exhibit aberrantly active Wnt signaling, we
      investigated the effect of the para-isomer of NO-ASA on CLL cell survival in
      vitro and in a CLL-like xenograft mouse model. EXPERIMENTAL DESIGN: Apoptosis in
      primary CLL cells was determined by flow cytometric annexin V-FITC (fluorescein
      isothiocyanate)/PI (propidium iodide) staining and immunoblotting of caspases,
      poly(ADP-ribose) polymerase (PARP), and antiapoptotic proteins. Interference of
      NO-ASA with Wnt/beta-catenin signaling was analyzed through immunoblots of
      different pathway members. Influence of caspase activation was investigated by
      pretreatment with a pan-caspase inhibitor. CLL-like JVM3 cells were
      subcutaneously inoculated into irradiated nude mice that were treated with 100 mg
      of para-NO-ASA/kg of body weight p.o. (by mouth) for 21 days. RESULTS: para-NO
      ASA induced apoptosis in CLL cells with an LC(50) (lethal concentration) of 8.72
      + 0.04 MUmol/L, whereas healthy blood cells were not affected. Furthermore, the
      compound induced caspase 9, caspase 3, and PARP cleavage. In addition, cleavage
      of beta-catenin and downregulation of beta-catenin/lymphoid enhancer factor (Lef)
      1 targets was observed. para-NO-ASA demonstrated strong antitumor efficacy in the
      xenograft mouse model with a tumor inhibtion rate of 83.4%. During therapy, no
      gross toxicity could be observed. CONCLUSIONS: para-NO-ASA selectively induces
      apoptosis in primary CLL cells and efficiently reduces tumor growth in a CLL-like
      xenograft model. As NO-ASA is orally available and is generally well tolerated,
      para-NO-ASA might be a promising new compound for CLL therapy.

PMID- 21097688
TI  - Dose and release pattern of anabolic implants affects growth of finishing beef
      steers across days on feed.
AB  - Four experiments evaluated the effect of implant dose and release pattern on
      performance and carcass traits of crossbred beef steers. In Exp. 1, steers (4 to
      7 pens/treatment; initial BW = 315 kg) were fed an average of 174 d. Treatments
      were 1) no implant (NI); 2) Revalor-S [120 mg of trenbolone acetate (TBA) and 24
      mg of estradiol 17beta (E(2)); REV-S]; 3) Revalor-IS followed by REV-S
      (cumulatively 200 mg of TBA and 40 mg of E(2); reimplanted at 68 to 74 d; REV
      IS/S); and 4) Revalor-XS (200 mg of TBA and 40 mg of E(2); REV-X). Carcass
      adjusted final BW was greater (P < 0.05) for REV-X and REV-IS/S than for REV-S
      (610, 609, and 598 kg, respectively). Daily DMI did not differ (P > 0.10) among
      the 3 implants, but carcass-adjusted G:F was greater (P < 0.05) for REV-X and REV
      IS/S than for REV-S (0.197 and 0.195 vs. 0.188). Both HCW and LM area were
      greater (P < 0.05) for REV-X and REV-IS/S than for REV-S. Marbling scores were
      greatest (P < 0.05) for REV-S and least (P < 0.05) for REV-IS/S; REV-X was
      intermediate to NI and REV-IS/S. In Exp. 2, steers (10 pens/treatment; initial BW
      = 391 kg) were fed 131 d, with treatments of REV-S, REV-IS/S (reimplanted at 44
      to 47 d), and REV-X. Carcass-adjusted final BW (598 kg), ADG (1.6 kg), DMI (9.4
      kg), G:F (0.17), and HCW did not differ (P > 0.10) among treatments. The
      percentage of Choice was less (P < 0.05) and percentage of Select greater (P <
      0.05) for REV-IS/S than for REV-S and REV-X. In Exp. 3, steers (10
      pens/treatment; initial BW = 277 kg) were fed 197 d and received either REV-IS/S
      (reimplanted at 90 to 103 d) or REV-X. Carcass-adjusted final BW (625 vs. 633 kg)
      and ADG (1.81 vs. 1.76 kg) were greater (P < 0.05) for REV-X-implanted steers.
      Daily DMI did not differ, but G:F tended (P < 0.10) to be increased and HCW was
      greater (P < 0.05) for REV-X than for REV-IS/S. In Exp. 4, steers (8
      pens/treatment; initial BW = 238 kg) were fed 243 d and received either REV-IS/S
      (reimplanted at 68 to 71 d) or REV-X. Carcass-adjusted final BW (612 kg), ADG
      (1.54 kg), DMI (7.55), and G:F (0.21) did not differ (P > 0.10) for REV-IS/S and
      REV-X-implanted steers. Carcass traits did not differ among implants, but the
      percentage of Choice carcasses was greater (P < 0.05) and percentage of Select
      was less (P < 0.05) for REV-X than for REV-IS/S. These data indicate that when
      TBA/E(2) dose is equal, the altered release rate of REV-X can improve performance
      and quality grade, but these effects depend on duration of the feeding period and
      timing of initial and terminal implants.

PMID- 21097690
TI  - High impact of Oatp1a/1b transporters on in vivo disposition of the hydrophobic
      anticancer drug paclitaxel.
AB  - PURPOSE: Organic anion-transporting polypeptides (OATP) mediate the cellular
      uptake of a broad range of drugs. The hydrophobic anticancer drug, paclitaxel
      (PTX), was recently identified as a substrate for OATP1B3 in vitro. We
      investigated the role of Oatp1a/1b transporters in the pharmacokinetics of PTX in
      vivo, as well as their impact at different dose levels of PTX and methotrexate
      (MTX). EXPERIMENTAL DESIGN: Recently generated Slco1a/1b(-/-) (lacking all
      Oatp1a/1b transporters) and wild-type mice were intravenously dosed with 2, 10,
      or 50 mg/kg of PTX, or with 10, 50, or 500 mg/kg of MTX, and plasma and tissue
      drug concentrations were measured. RESULTS: In spite of its hydrophobicity, PTX
      systemic exposure (at 10 mg/kg) was increased by greater than 2-fold in
      Slco1a/1b(-/-) mice compared with wild-type, whereas PTX liver uptake was reduced
      by about 2-fold. Oatp1a/1b transporters displayed a high impact on PTX and MTX
      pharmacokinetics over a broad dose range. For MTX, even at 500 mg/kg, saturation
      of Oatp1a/1b was not observed, with a 3.4-fold increase in plasma and 30-fold
      decrease in liver levels in Slco1a/1b(-/-) mice compared with wild-type. Although
      beginning saturation of Oatp1a/1b was observed at the highest dose of PTX, plasma
      levels in Slco1a/1b(-/-) mice were still 1.7-fold increased and liver levels 1.5
      fold decreased compared with wild-type. CONCLUSION: Oatp1a/1b transporters play a
      pronounced role in determining plasma levels and tissue distribution of MTX and
      PTX, thus affecting even highly hydrophobic drugs. Variation in OATP1A/1B
      transporter activity, due to genetic variation, inhibition, and/or tumor
      expression might affect toxicity and therapeutic efficacy of these anticancer
      drugs.

PMID- 21097691
TI  - Extent and patterns of MGMT promoter methylation in glioblastoma- and respective
      glioblastoma-derived spheres.
AB  - PURPOSE: Quantitative methylation-specific tests suggest that not all cells in a
      glioblastoma with detectable promoter methylation of the O6-methylguanine DNA
      methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation
      may indicate cell subpopulations with distinct MGMT status, raising the question
      of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic
      silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl
      guanine and has been shown to be a predictive factor for benefit from alkylating
      agent therapy in glioblastoma. EXPERIMENTAL DESIGN: Ten paired samples of
      glioblastoma and respective glioblastoma-derived spheres (GS), cultured under
      stem cell conditions, were analyzed for the degree and pattern of MGMT promoter
      methylation by methylation-specific clone sequencing, MGMT gene dosage, chromatin
      status, and respective effects on MGMT expression and MGMT activity. RESULTS: In
      glioblastoma, MGMT-methylated alleles ranged from 10% to 90%. In contrast,
      methylated alleles were highly enriched (100% of clones) in respective GS, even
      when 2 MGMT alleles were present, with 1 exception (<50%). The CpG methylation
      patterns were characteristic for each glioblastoma exhibiting 25% to 90%
      methylated CpGs of 28 sites interrogated. Furthermore, MGMT promoter methylation
      was associated with a nonpermissive chromatin status in accordance with very low
      MGMT transcript levels and undetectable MGMT activity. CONCLUSIONS: In MGMT
      methylated glioblastoma, MGMT promoter methylation is highly enriched in GS that
      supposedly comprise glioma-initiating cells. Thus, even a low percentage of MGMT
      methylation measured in a glioblastoma sample may be relevant and predict benefit
      from an alkylating agent therapy.

PMID- 21097692
TI  - Genetic polymorphisms associated with a prolonged progression-free survival in
      patients with metastatic renal cell cancer treated with sunitinib.
AB  - PURPOSE: The objective of this study was to identify genetic polymorphisms
      related to the pharmacokinetics and pharmacodynamics of sunitinib that are
      associated with a prolonged progression-free survival (PFS) and/or overall
      survival (OS) in patients with clear-cell metastatic renal cell cancer (mRCC)
      treated with sunitinib. EXPERIMENTAL DESIGN: A retrospective multicenter
      pharmacogenetic association study was performed in 136 clear-cell mRCC patients
      treated with sunitinib. A total of 30 polymorphisms in 11 candidate genes,
      together with clinical characteristics were tested univariately for association
      with PFS as primary and OS as secondary outcome. Candidate variables with P < 0.1
      were analyzed in a multivariate Cox regression model. RESULTS: Multivariate
      analysis showed that PFS was significantly improved when an A-allele was present
      in CYP3A5 6986A/G [hazard ratio (HR), 0.27; P = 0.032], a CAT copy was absent in
      the NR1I3 haplotype (5719C/T, 7738A/C, 7837T/G; HR, 1.76; P = 0.017) and a TCG
      copy was present in the ABCB1 haplotype (3435C/T, 1236C/T, 2677G/T; HR, 0.52; P =
      0.033). Carriers with a favorable genetic profile (n = 95) had an improved PFS
      and OS as compared with noncarriers (median PFS and OS: 13.1 versus 7.5 months
      and 19.9 versus 12.3 months). Next to the genetic variants, the Memorial Sloan
      Kettering Cancer Center prognostic criteria were associated with PFS and OS (HR,
      1.99 and 2.27; P < 0.001). CONCLUSIONS: This exploratory study shows that genetic
      polymorphisms in three genes involved in sunitinib pharmacokinetics are
      associated with PFS in mRCC patients treated with this drug. These findings
      advocate prospective validation and further elucidation of these genetic
      determinants in relation to sunitinib exposure and efficacy.

PMID- 21097693
TI  - Tumor growth inhibition by olaparib in BRCA2 germline-mutated patient-derived
      ovarian cancer tissue xenografts.
AB  - PURPOSE: Most patients with ovarian carcinomas succumb to their disease and there
      is a critical need for improved therapeutic approaches. Carcinomas arising in
      BRCA mutation carriers display defective DNA double-strand break repair that can
      be therapeutically exploited by inhibition of PARP-1, a key enzyme in the repair
      of DNA single-strand breaks, creating synthetic lethality in tumor cells.
      EXPERIMENTAL DESIGN: To investigate synthetic lethality in vivo, we established a
      BRCA2 germline-mutated xenograft model that was developed directly from human
      ovarian cancer tissue, treated with the PARP inhibitor olaparib (AZD2281) alone
      and in combination with carboplatin. RESULTS: We show that olaparib alone and in
      combination with carboplatin greatly inhibit growth in BRCA2-mutated ovarian
      serous carcinoma. This effect was not observed in a serous carcinoma with normal
      BRCA function, showing a specific antitumor effect of olaparib in mutation
      carriers. Immunohistochemistry (cleaved caspase-3 and Ki-67 stains) of remnant
      tissue after olaparib treatment revealed significantly decreased proliferation
      and increased apoptotic indices in these tumors compared with untreated controls.
      Furthermore, olaparib-treated tumors showed highly reduced PARP-1 activity that
      correlated with olaparib levels. CONCLUSIONS: We established a BRCA2-mutated
      human ovarian cancer xenograft model suitable for experimental drug testing. The
      demonstrated in vivo efficacy of olaparib extends on the preclinical rationale
      for further clinical trials targeting ovarian cancer patients with BRCA
      mutations.

PMID- 21097694
TI  - Innate and adaptive interleukin-17-producing lymphocytes in chronic inflammatory
      lung disorders.
AB  - During T-cell receptor activation in a particular cytokine environment, naive
      CD4+ T cells may differentiate into lineages defined by their pattern of cytokine
      production and transcription factors: T helper type 1 (Th1), Th2, Th17, and Th22
      cells; follicular helper T cells; and inducible regulatory T cells. Th17 cells
      have been recognized as a distinct lineage of Th cells, and associations between
      IL-17 and human disease have been known somewhat longer. It would be an
      oversimplification to restrict IL-17 to Th17 cells. Indeed, IL-17 is also
      expressed by other cells including IL-17-producing gammadelta T (gammadelta T-17)
      cells, natural killer T-17 cells, and IL-17-producing lymphoid tissue-induced
      cells. IL-17 was cloned in 1995 as a cytokine expressed by T cells, exerting
      inflammatory effects on epithelial, endothelial, and fibroblast cells. IL-17 is a
      solid link between innate and adaptive immunity and can exert both beneficial and
      deleterious effects. The discovery of IL-17 T cells has provided exciting new
      insights into host defense, immunoregulation, and autoimmunity. Unquestionably,
      data from mouse models have contributed enormously to our insight into
      immunological mechanisms. However, because of numerous differences between murine
      and human immunology, data obtained in mice are not simply interchangeable. We
      review IL-17 T cells exclusively in the human situation and more specifically
      their potential role in respiratory diseases. The advances in our understanding
      of IL-17 regulation offer opportunities to dissect the human IL-17 system and to
      reflect on the clinical presentation of lung diseases. More importantly, the IL
      17 system allows us to speculate on new therapeutic opportunities. Some results
      have been previously reported in an abstract.

PMID- 21097695
TI  - Vasoactive drugs in circulatory shock.
AB  - Shock occurs when failure of the cardiovascular system compromises tissue
      perfusion. When fluid administration fails to restore adequate arterial pressure
      and organ perfusion in patients with shock, therapy with vasoactive agents should
      be initiated. The key to selecting among vasoactive agents is to make the choice
      in the context of the goals of therapy. The ultimate goals of hemodynamic therapy
      in shock are to restore effective tissue perfusion and to normalize cellular
      metabolism. The clinician needs to consider ways of achieving those goals and the
      mechanisms of action of potential therapies. Armed with this knowledge, it
      becomes easier to match the mechanism of action of a particular agent to the
      goals of therapy. When this is done, differences among various agents are seen
      primarily as differences in mechanisms of action, and discussions about which
      agent is "best" are transformed into consideration of which agent is best suited
      to implement the therapeutic strategy that has been selected in a given clinical
      context. Despite the complex pathophysiology of shock, use of vasoactive agents
      for hemodynamic support of patients with shock can be guided by an underlying
      approach in which clinicians define specific goals and end points, titrate
      therapies to those end points, and evaluate the results of their interventions on
      an ongoing basis.

PMID- 21097697
TI  - The paradox of the neutrophil's role in tissue injury.
AB  - The neutrophil is an essential component of the innate immune system, and its
      function is vital to human life. Its production increases in response to
      virtually all forms of inflammation, and subsequently, it can accumulate in blood
      and tissue to varying degrees. Although its participation in the inflammatory
      response is often salutary by nature of its normal interaction with vascular
      endothelium and its capability to enter tissues and respond to chemotactic
      gradients and to phagocytize and kill microrganisms, it can contribute to
      processes that impair vascular integrity and blood flow. The mechanisms that the
      neutrophil uses to kill microorganisms also have the potential to injure normal
      tissue under special circumstances. Its paradoxical role in the pathophysiology
      of disease is particularly, but not exclusively, notable in seven circumstances:
      1) diabetic retinopathy, 2) sickle cell disease, 3) TRALI, 4) ARDS, 5) renal
      microvasculopathy, 6) stroke, and 7) acute coronary artery syndrome. The
      activated neutrophil's capability to become adhesive to endothelium, to generate
      highly ROS, and to secrete proteases gives it the potential to induce local
      vascular and tissue injury. In this review, we summarize the evidence for its
      role as a mediator of tissue injury in these seven conditions, making it or its
      products potential therapeutic targets.

PMID- 21097696
TI  - Anti-tissue antibodies are related to lung function in chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a multicomponent
      disease. Autoimmunity can contribute to the pathogenesis of COPD. OBJECTIVES:
      This study investigates the prevalence of circulating antinuclear antibodies
      (ANA) and anti-tissue (AT) antibodies, two common markers of autoimmunity, in
      COPD and their relationship with several components of the disease. METHODS: We
      determined lung function, the serum titers of ANA and AT by immunofluorescence,
      and the serum levels of C-reactive protein (CRP) by high sensitivity nephelometry
      in 328 patients with clinically stable COPD and in 67 healthy controls recruited
      in the PAC-COPD study. Multiple linear and logistic regression analysis was used
      to analyze results. MEASUREMENTS AND MAIN RESULTS: The prevalence of abnormal ANA
      and AT titers was 34% and 26% in patients and 3% and 6% in controls,
      respectively. Levels of AT greater than or equal to 1:320 were seen in 21% of
      patients with COPD and were independently associated with the severity of airflow
      limitation and gas transfer impairment (P < 0.05). Neither ANA or AT titers was
      related to body mass index, current smoking status, use of inhaled steroids, the
      Charlson index, or serum C-reactive protein values. CONCLUSIONS: Between a
      quarter and a third of patients with clinically stable COPD present abnormal
      titers of circulating ANA and AT. The observed relationship between AT and lung
      function supports a role for autoimmunity in the pathogenesis of COPD.

PMID- 21097698
TI  - Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and
      differentially modulated by IL-10.
AB  - PD-1 plays an important role in T cell exhaustion during HIV infection. PD-1 has
      two ligands: PD-L1, expressed on hematopoietic and nonhematopoietic cells, and PD
      L2, limited to DCs and macrophages. Little is known about PD-L1 expression and
      regulation in human macrophages. Previous reports have found few immediate
      effects of macrophage exposure to HIV, suggesting that macrophages lack PRRs for
      this virus. Using quantitative confocal microscopy and a multiplexed cytokine
      bead array, we measured induction of PD-L1, PD-L2, and innate response cytokines
      in human MDMs in response to chemically inactivated HIV virions. Consistent with
      previous reports, no cytokines were induced by HIV virion exposure. Whereas PD-L1
      and PD-L2 had low baseline expression, TLR ligands (LPS and CL097) up-regulated
      PD-L1 but not PD-L2. Unlike what we found for cytokine expression, PD-L1 and PD
      L2 were up-regulated in response to exposure with inactivated HIV virions or with
      replication-competent HIV. Expression of PD-L1 was differentially modulated by IL
      10, which induced up-regulation of PD-L1 but not of PD-L2, and IL-10 blockade
      enhanced only PD-L2 expression. We discuss implications for innate recognition of
      HIV by macrophages and potential, different roles for PD-L1 and PD-L2 in immunity
      and pathogenesis.

PMID- 21097699
TI  - Replication error deficient and proficient colorectal cancer gene expression
      differences caused by 3'UTR polyT sequence deletions.
AB  - Replication error deficient (RER+) colorectal cancers are a distinct subset of
      colorectal cancers, characterized by inactivation of the DNA mismatch repair
      system. These cancers are typically pseudodiploid, accumulate mutations in
      repetitive sequences as a result of their mismatch repair deficiency, and have
      distinct pathologies. Regulatory sequences controlling all aspects of mRNA
      processing, especially including message stability, are found in the 3'UTR
      sequence of most genes. The relevant sequences are typically A/U-rich elements or
      U repeats. Microarray analysis of 14 RER+ (deficient) and 16 RER- (proficient)
      colorectal cancer cell lines confirms a striking difference in expression
      profiles. Analysis of the incidence of mononucleotide repeat sequences in the
      3'UTRs, 5'UTRs, and coding sequences of those genes most differentially expressed
      in RER+ versus RER- cell lines has shown that much of this differential
      expression can be explained by the occurrence of a massive enrichment of genes
      with 3'UTR T repeats longer than 11 base pairs in the most differentially
      expressed genes. This enrichment was confirmed by analysis of two published
      consensus sets of RER differentially expressed probesets for a large number of
      primary colorectal cancers. Sequence analysis of the 3'UTRs of a selection of the
      most differentially expressed genes shows that they all contain deletions in
      these repeats in all RER+ cell lines studied. These data strongly imply that
      deregulation of mRNA stability through accumulation of mutations in repetitive
      regulatory 3'UTR sequences underlies the striking difference in expression
      profiles between RER+ and RER- colorectal cancers.

PMID- 21097700
TI  - Type II protein arginine methyltransferase 5 (PRMT5) is required for circadian
      period determination in Arabidopsis thaliana.
AB  - Posttranslational modification is an important element in circadian clock
      function from cyanobacteria through plants and mammals. For example, a number of
      key clock components are phosphorylated and thereby marked for subsequent
      ubiquitination and degradation. Through forward genetic analysis we demonstrate
      that protein arginine methyltransferase 5 (PRMT5; At4g31120) is a critical
      determinant of circadian period in Arabidopsis. PRMT5 is coregulated with a set
      of 1,253 genes that shows alterations in phase of expression in response to
      entrainment to thermocycles versus photocycles in constant temperature. PRMT5
      encodes a type II protein arginine methyltransferase that catalyzes the symmetric
      dimethylation of arginine residues (Rsme2). Rsme2 modification has been observed
      in many taxa, and targets include histones, components of the transcription
      complex, and components of the spliceosome. Neither arginine methylation nor
      PRMT5 has been implicated previously in circadian clock function, but the period
      lengthening associated with mutational disruption of prmt5 indicates that Rsme2
      is a decoration important for the Arabidopsis clock and possibly for clocks in
      general.

PMID- 21097701
TI  - Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle
      assembly by engaging in organelle-specific Aurora A activation.
AB  - Centrosomes are primary microtubule (MT)-organizing centers (MTOCs). During
      mitosis, they dramatically increase their size and MT-nucleating activity and
      participate in spindle assembly from spindle poles. These events require the
      serine/threonine kinase, Aurora A (AurA), and the centrosomal protein of 192 kDa
      (Cep192)/spindle defective 2 (Spd-2), but the underlying mechanism remains
      unclear. We have found that Cep192, unlike targeting protein for Xklp2 (TPX2), a
      known MT-localizing AurA activator, is an AurA cofactor in centrosome-driven
      spindle assembly. Cep192, through a direct interaction, targets AurA to mitotic
      centrosomes where the locally accumulating AurA forms homodimers or oligomers.
      The dimerization of endogenous AurA, in the presence of bound Cep192, triggers
      potent kinase activation that, in turn, drives MT assembly. Depletion of Cep192
      or specific interference with AurA-Cep192 binding did not prevent AurA
      oligomerization on MTs but abrogated AurA recruitment to centrosomes and its
      activation by either sperm nuclei or anti-AurA antibody (alphaAurA)-induced
      dimerization. In these settings, MT assembly by both centrosomes and alphaAurA
      coated beads was also abolished or severely compromised. Hence, Cep192 activates
      AurA by a mechanism different from that previously described for TPX2. The Cep192
      mediated mechanism maximizes AurA activity at centrosomes and appears essential
      for the function of these organelles as MTOCs.

PMID- 21097703
TI  - CO impedes superfast O2 binding in ba3 cytochrome oxidase from Thermus
      thermophilus.
AB  - Kinetic studies of heme-copper terminal oxidases using the CO flow-flash method
      are potentially compromised by the fate of the photodissociated CO. In this time
      resolved optical absorption study, we compared the kinetics of dioxygen reduction
      by ba(3) cytochrome c oxidase from Thermus thermophilus in the absence and
      presence of CO using a photolabile O(2)-carrier. A novel double-laser excitation
      is introduced in which dioxygen is generated by photolyzing the O(2)-carrier with
      a 355 nm laser pulse and the fully reduced CO-bound ba(3) simultaneously with a
      second 532-nm laser pulse. A kinetic analysis reveals a sequential mechanism in
      which O(2) binding to heme a(3) at 90 MUM O(2) occurs with lifetimes of 9.3 and
      110 MUs in the absence and presence of CO, respectively, followed by a faster
      cleavage of the dioxygen bond (4.8 MUs), which generates the P intermediate with
      the concomitant oxidation of heme b. The second-order rate constant of 1 * 10(9)
      M(-1) s(-1) for O(2) binding to ba(3) in the absence of CO is 10 times greater
      than observed in the presence of CO as well as for the bovine heart enzyme. The
      O(2) bond cleavage in ba(3) of 4.8 MUs is also approximately 10 times faster than
      in the bovine enzyme. These results suggest important structural differences
      between the accessibility of O(2) to the active site in ba(3) and the bovine
      enzyme, and they demonstrate that the photodissociated CO impedes access of
      dioxygen to the heme a(3) site in ba(3), making the CO flow-flash method
      inapplicable.

PMID- 21097704
TI  - Artificial atoms on semiconductor surfaces.
AB  - Semiconductor nanocrystals are called artificial atoms because of their atom-like
      discrete electronic structure resulting from quantum confinement. Artificial
      atoms can also be assembled into artificial molecules or solids, thus, extending
      the toolbox for material design. We address the interaction of artificial atoms
      with bulk semiconductor surfaces. These interfaces are model systems for
      understanding the coupling between localized and delocalized electronic
      structures. In many perceived applications, such as nanoelectronics,
      optoelectronics, and solar energy conversion, interfacing semiconductor
      nanocrystals to bulk materials is a key ingredient. Here, we apply the well
      established theories of chemisorption and interfacial electron transfer as
      conceptual frameworks for understanding the adsorption of semiconductor
      nanocrystals on surfaces, paying particular attention to instances when the
      nonadiabatic Marcus picture breaks down. We illustrate these issues using recent
      examples from our laboratory.

PMID- 21097705
TI  - Energetics and mechanisms of folding and flipping the myristoyl switch in the
      {beta}-trefoil protein, hisactophilin.
AB  - Myristoylation, the covalent linkage of a saturated, C(14) fatty acyl chain to
      the N-terminal glycine in a protein, plays a vital role in reversible membrane
      binding and signaling by the modified proteins. Currently, little is known about
      the effects of myristoylation on protein folding and stability, or about the
      energetics and molecular mechanisms of switching involving states with
      sequestered versus accessible myristoyl group. Our analysis of these effects in
      hisactophilin, a histidine-rich protein that binds cell membranes and actin in a
      pH-dependent manner, shows that myristoylation significantly increases
      hisactophilin stability, while also markedly increasing global protein folding
      and unfolding rates. The switching between sequestered and accessible states is
      pH dependent, with an apparent pK(switch) of 6.95, and an apparent free energy
      change of 2.0 kcal.mol(-1). The myristoyl switch is linked to the reversible
      uptake of ~1.5 protons, likely by histidine residues. This pH dependence of
      switching appears to be the physical basis of the sensitive, pH-dependent
      regulation of membrane binding observed in vivo. We conclude that an increase in
      protein stability upon modification and burial of the attached group is likely to
      occur in numerous proteins modified with fatty acyl or other hydrophobic groups,
      and that the biophysical effects of such modification are likely to play an
      important role in their functional switches. In addition, the increased global
      dynamics caused by myristoylation of hisactophilin reveals a general mechanism
      whereby hydrophobic moieties can make nonnative interactions or relieve strain in
      transition states, thereby increasing the rates of interconversion between
      different states.

PMID- 21097706
TI  - Self-assembly of metal nanostructures on binary alloy surfaces.
AB  - Deposition of metals on binary alloy surfaces offers new possibilities for
      guiding the formation of functional metal nanostructures. This idea is explored
      with scanning tunneling microscopy studies and atomistic-level analysis and
      modeling of nonequilibrium island formation. For Au/NiAl(110), complex monolayer
      structures are found and compared with the simple fcc(110) bilayer structure
      recently observed for Ag/NiAl(110). We also consider a more complex codeposition
      system, (Ni + Al)/NiAl(110), which offers the opportunity for fundamental studies
      of self-growth of alloys including deviations for equilibrium ordering. A general
      multisite lattice-gas model framework enables analysis of structure selection and
      morphological evolution in these systems.

PMID- 21097707
TI  - Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor
      CD34+ cells.
AB  - Etoposide is a widely used anticancer drug successfully used for the treatment of
      many types of cancer in children and adults. Its use, however, is associated with
      an increased risk of development of secondary acute myelogenous leukemia
      involving the mixed-lineage leukemia (MLL) gene (11q23) translocations. Previous
      studies demonstrated that the phenoxyl radical of etoposide can be produced by
      action of myeloperoxidase (MPO), an enzyme found in developing myeloid progenitor
      cells, the likely origin for myeloid leukemias. We hypothesized, therefore, that
      one-electron oxidation of etoposide by MPO to its phenoxyl radical is important
      for converting this anticancer drug to genotoxic and carcinogenic species in
      human CD34(+) myeloid progenitor cells. In the present study, using electron
      paramagnetic resonance spectroscopy, we provide conclusive evidence for MPO
      dependent formation of etoposide phenoxyl radicals in growth factor-mobilized
      CD34(+) cells isolated from human umbilical cord blood and demonstrate that MPO
      induced oxidation of etoposide is amplified in the presence of phenol. Formation
      of etoposide radicals resulted in the oxidation of endogenous thiols, thus
      providing evidence for etoposide-mediated MPO-catalyzed redox cycling that may
      play a role in enhanced etoposide genotoxicity. In separate studies, etoposide
      induced DNA damage and MLL gene rearrangements were demonstrated to be dependent
      in part on MPO activity in CD34(+) cells. Together, our results are consistent
      with the idea that MPO-dependent oxidation of etoposide in human hematopoietic
      CD34(+) cells makes these cells especially prone to the induction of etoposide
      related acute myeloid leukemia.

PMID- 21097708
TI  - Spermidine is a morphogenetic determinant for cell fate specification in the male
      gametophyte of the water fern Marsilea vestita.
AB  - Here, we show that the polyamine spermidine plays a key role as a morphogenetic
      determinant during spermatid development in the water fern Marsilea vestita.
      Spermidine levels rise first in sterile jacket cells and then increase
      dramatically in spermatogenous cells as the spermatids mature. RNA interference
      and drug treatments were employed to deplete spermidine in the gametophyte at
      different stages of gametogenesis. Development in spermidine-depleted
      gametophytes was arrested before the completion of the last round of cell
      divisions. In spermidine-depleted spermatogenous cells, chromatin failed to
      condense properly, basal body positioning was altered, and the microtubule ribbon
      was in disarray. When cyclohexylamine, a spermidine synthase (SPDS) inhibitor,
      was added at the start of spermatid differentiation, the spermatid nuclei
      remained round, centrin failed to localize into basal bodies, thus blocking basal
      body formation, and the microtubule ribbon was completely abolished. In untreated
      gametophytes, spermidine made in the jacket cells moves into the spermatids,
      where it is involved in the unmasking of stored SPDS mRNAs, leading to
      substantial spermidine synthesis in the spermatids. We found that treating spores
      directly with spermidine or other polyamines was sufficient to unmask a variety
      of stored mRNAs in gametophytes and arrest development. Differences in patterns
      of transcript distribution after these treatments suggest that specific
      transcripts reside in different locations in the dry spore; these differences may
      be linked to the timing of unmasking and translation for that mRNA during
      development.

PMID- 21097709
TI  - Arabidopsis transcription factor ELONGATED HYPOCOTYL5 plays a role in the
      feedback regulation of phytochrome A signaling.
AB  - Phytochrome A (phyA) is the primary photoreceptor responsible for perceiving and
      mediating various responses to far-red light in Arabidopsis thaliana. FAR-RED
      ELONGATED HYPOCOTYL1 (FHY1) and its homolog FHY1-LIKE (FHL) are two small plant
      specific proteins essential for light-regulated phyA nuclear accumulation and
      subsequent phyA signaling processes. FHY3 and its homolog FAR-RED IMPAIRED
      RESPONSE1 (FAR1) are two transposase-derived transcription factors that directly
      activate FHY1/FHL transcription and thus mediate subsequent phyA nuclear
      accumulation and responses. Here, we report that ELONGATED HYPOCOTYL5 (HY5), a
      well-characterized bZIP transcription factor involved in promoting
      photomorphogenesis, directly binds ACGT-containing elements a few base pairs away
      from the FHY3/FAR1 binding sites in the FHY1/FHL promoters. We demonstrate that
      HY5 physically interacts with FHY3/FAR1 through their respective DNA binding
      domains and negatively regulates FHY3/FAR1-activated FHY1/FHL expression under
      far-red light. Together, our data show that HY5 plays a role in negative feedback
      regulation of phyA signaling by attenuating FHY3/FAR1-activated FHY1/FHL
      expression, providing a mechanism for fine-tuning phyA signaling homeostasis.

PMID- 21097710
TI  - ABI4 mediates abscisic acid and cytokinin inhibition of lateral root formation by
      reducing polar auxin transport in Arabidopsis.
AB  - Key steps in a plant's development and adaptation to the environment are the
      initiation and development of lateral roots (LRs). LR development is regulated by
      auxin, the major plant hormone promoting LR formation, its counteracting hormones
      cytokinin, and abscisic acid (ABA). Here, we show that mutating ABSCISIC ACID
      INSENSITIVE4 (ABI4), which encodes an ABA-regulated AP2 domain transcription
      factor, results in an increased number of LRs. We show that ABI4 is expressed in
      roots and that its overexpression impairs LR development. Root expression of ABI4
      is enhanced by ABA, and cytokinin and is repressed by auxin. Using hormone
      response promoters, we show that ABI4 also affects auxin and cytokinin profiles
      in the root. Furthermore, LR development in abi4 mutants is not altered or
      inhibited by cytokinin or ABA. Expression of the auxin-efflux carrier protein
      PIN1 is reduced in ABI4 overexpressors, enhanced in abi4 mutants, and is less
      sensitive to inhibition by cytokinin and ABA in abi4 mutants than in wild-type
      plants. Transport levels of exogenously applied auxin were elevated in abi4
      mutants and reduced in ABI4 overexpressors. We therefore suggest that ABI4
      mediates ABA and cytokinin inhibition of LR formation via reduction of polar
      auxin transport and that the resulting decrease in root auxin leads to a
      reduction in LR development.

PMID- 21097711
TI  - Members of the LATERAL ORGAN BOUNDARIES DOMAIN transcription factor family are
      involved in the regulation of secondary growth in Populus.
AB  - Regulation of secondary (woody) growth is of substantial economic and
      environmental interest but is poorly understood. We identified and subsequently
      characterized an activation-tagged poplar (Populus tremula * Populus alba) mutant
      with enhanced woody growth and changes in bark texture caused primarily by
      increased secondary phloem production. Molecular characterization of the mutation
      through positioning of the tag and retransformation experiments shows that the
      phenotype is conditioned by activation of an uncharacterized gene that encodes a
      novel member of the LATERAL ORGAN BOUNDARIES DOMAIN (LBD) family of transcription
      factors. Homology analysis showed highest similarity to an uncharacterized LBD1
      gene from Arabidopsis thaliana, and we consequently named it Populus tremula *
      Populus alba (Pta) LBD1. Dominant-negative suppression of Pta LBD1 via
      translational fusion with the repressor SRDX domain caused decreased diameter
      growth and suppressed and highly irregular phloem development. In wild-type
      plants, LBD1 was most highly expressed in the phloem and cambial zone. Two key
      Class I KNOTTED1-like homeobox genes that promote meristem identity in the
      cambium were downregulated, while an Altered Phloem Development gene that is
      known to promote phloem differentiation was upregulated in the mutant. A set of
      four LBD genes, including the LBD1 gene, was predominantly expressed in wood
      forming tissues, suggesting a broader regulatory role of these transcription
      factors during secondary woody growth in poplar.

PMID- 21097712
TI  - Amino acid homeostasis modulates salicylic acid-associated redox status and
      defense responses in Arabidopsis.
AB  - The tight association between nitrogen status and pathogenesis has been broadly
      documented in plant-pathogen interactions. However, the interface between primary
      metabolism and disease responses remains largely unclear. Here, we show that
      knockout of a single amino acid transporter, LYSINE HISTIDINE TRANSPORTER1
      (LHT1), is sufficient for Arabidopsis thaliana plants to confer a broad spectrum
      of disease resistance in a salicylic acid-dependent manner. We found that redox
      fine-tuning in photosynthetic cells was causally linked to the lht1 mutant
      associated phenotypes. Furthermore, the enhanced resistance in lht1 could be
      attributed to a specific deficiency of its main physiological substrate, Gln, and
      not to a general nitrogen deficiency. Thus, by enabling nitrogen metabolism to
      moderate the cellular redox status, a plant primary metabolite, Gln, plays a
      crucial role in plant disease resistance.

PMID- 21097713
TI  - Melanoma chemoprevention in skin reconstructs and mouse xenografts using
      isoselenocyanate-4.
AB  - Melanoma incidence and mortality rates continue to increase despite the use of
      sunscreen as well as screening programs for early surgical excision of
      premalignant lesions. The steady increase in melanoma incidence suggests that
      additional preventive approaches are needed to augment these existing strategies.
      One unexplored area involves targeting genes whose deregulation promotes disease
      development to prevent melanoma. The Akt3 signaling pathway is one key signaling
      cascade that plays a central role by deregulating apoptosis to promote
      development of approximately 70% of melanomas. Isoselenocyanate-4 (ISC-4),
      derived from isothiocyanates by increasing the alkyl chain length and replacing
      sulfur with selenium, has been developed to target this important signaling
      pathway in melanomas; however, its chemopreventive potential is unknown. In this
      study, the chemopreventive efficacy of topical ISC-4 was evaluated in a
      laboratory-generated human skin melanoma model containing early melanocytic
      lesion or advanced stage melanoma cell lines and in animals containing invasive
      xenografted human melanoma. Repeated topical application of ISC-4 reduced tumor
      cell expansion in the skin model by 80% to 90% and decreased tumor development in
      animals by approximately 80%. Histologic examination of ISC-4-treated skin showed
      no obvious damage to skin cells or skin morphology, and treated animals did not
      exhibit markers indicative of major organ-related toxicity. Mechanistically, ISC
      4 prevented melanoma by decreasing Akt3 signaling that lead to a 3-fold increase
      in apoptosis rates. Thus, topical ISC-4 can delay or slow down melanocytic lesion
      or melanoma development in preclinical models and could impact melanoma incidence
      rates if similar results are observed in humans.

PMID- 21097715
TI  - Histopathologic features, immunophenotyping, clonality, and eubacterial
      fluorescence in situ hybridization in cats with lymphocytic
      cholangitis/cholangiohepatitis.
AB  - Feline lymphocytic cholangitis is a poorly characterized disease complex with
      respect to histologic lesions, immunophenotype, and etiopathogenesis. Seventy
      eight cases of feline lymphocytic cholangitis (n = 51) and feline hepatic
      lymphoma (n = 27) were reviewed using standardized histopathology,
      immunophenotyping (B cell and T cell), polymerase chain reaction for T-cell
      receptor (TCR) gene rearrangement, and fluorescence in situ hybridization (FISH)
      for eubacteria. Five histopathologic features in cases of lymphocytic cholangitis
      assisted in its differentiation from hepatic lymphoma: bile duct targeting (n =
      32, 62.7%), ductopenia (n = 9, 17.6%), peribiliary fibrosis (n = 37, 72.5%),
      portal B-cell aggregates (n = 36, 70.6%), and portal lipogranulomas (n = 38,
      74.5%). The majority of lymphocytic cholangitis cases (n = 35, 68.6%) were T cell
      predominant; 15 (29.4%) had an equal mix of B cells and T cells, and 1 (1.9%) had
      a B cell-predominant infiltrate; 66.6% of hepatic lymphoma cases were T-cell
      lymphomas. TCR clonality results were unexpected, with 17.1% of cases of
      lymphocytic cholangitis having clonal or oligoclonal populations and with T-cell
      lymphomas having variable TCR clonality (63.6% clonal or oligoclonal, 36.3%
      polyclonal). The majority of lymphocytic cholangitis (n = 32 of 36, 88.8%) and
      all hepatic lymphoma cases had no detectable eubacteria using FISH. As
      demonstrated here, bile duct targeting, ductopenia, peribiliary fibrosis, portal
      B-cell aggregates, and portal lipogranulomas are lymphocytic cholangitis features
      that, along with polyclonal TCR (83%), help differentiate it from hepatic
      lymphoma. No strong evidence was found implicating in situ bacterial colonization
      as an etiopathogenesis of lymphocytic cholangitis.

PMID- 21097714
TI  - Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small
      cell lung cancer growth and metastasis.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths
      worldwide; however, only limited therapeutic treatments are available. Hence, we
      investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic
      targets against NSCLC. We observed expression of CB1 (24%) and CB2 (55%) in NSCLC
      patients. Furthermore, we have shown that the treatment of NSCLC cell lines (A549
      and SW-1573) with CB1/CB2- and CB2-specific agonists Win55,212-2 and JWH-015,
      respectively, significantly attenuated random as well as growth factor-directed
      in vitro chemotaxis and chemoinvasion in these cells. We also observed
      significant reduction in focal adhesion complex, which plays an important role in
      migration, upon treatment with both JWH-015 and Win55,212-2. In addition,
      pretreatment with CB1/CB2 selective antagonists, AM251 and AM630, prior to JWH
      015 and Win55,212-2 treatments, attenuated the agonist-mediated inhibition of in
      vitro chemotaxis and chemoinvasion. In addition, both CB1 and CB2 agonists
      Win55,212-2 and JWH-133, respectively, significantly inhibited in vivo tumor
      growth and lung metastasis (~50%). These effects were receptor mediated, as
      pretreatment with CB1/CB2 antagonists abrogated CB1/CB2 agonist-mediated effects
      on tumor growth and metastasis. Reduced proliferation and vascularization, along
      with increased apoptosis, were observed in tumors obtained from animals treated
      with JWH-133 and Win55,212-2. Upon further elucidation into the molecular
      mechanism, we observed that both CB1 and CB2 agonists inhibited phosphorylation
      of AKT, a key signaling molecule controlling cell survival, migration, and
      apoptosis, and reduced matrix metalloproteinase 9 expression and activity. These
      results suggest that CB1 and CB2 could be used as novel therapeutic targets
      against NSCLC.

PMID- 21097716
TI  - Osteoporosis associated with pulmonary silicosis in an equine bone fragility
      syndrome.
AB  - California horses incur a bone fragility syndrome manifested by pathologic
      fractures. This study investigated gross, radiographic, and histologic features
      of the disorder as well as relationships with silicosis and levels of heavy
      metals and trace minerals through a postmortem study of 9 affected and 3
      unaffected horses. Bones and soft tissues were evaluated grossly and
      histologically. Bones, lymph nodes, and lung tissue were evaluated
      radiographically. Tissues were evaluated for silicon levels, intracytoplasmic
      crystals, heavy metals, and trace minerals. All 9 affected horses had
      osteoporosis and clinical or subclinical pulmonary disease due to silicosis (8/9)
      or pneumoconiosis (1/9). All affected horses had radiographic findings consistent
      with osteopenia and histologic evidence of osteoporosis characterized by
      osteopenia, numerous resorption cavities, cement lines, and a mosaic lamellar
      pattern indicative of multiple remodeling events. Silicosis was characterized by
      widespread pulmonary granuloma formation with fibrosis; variable
      tracheobronchiolar and mediastinal granulomatous lymphadenitis; intracellular
      crystals within lung and lymph node macrophages; and pronounced lymph node
      fibrosis, focal necrosis, and dystrophic calcification. Crystals in lung (6/9)
      and lymph node (8/9) tissues were identified as cytotoxic silica dioxide
      polymorphs. Lung and liver tissue from affected horses had elevated levels of
      elemental silicon. Osteoporosis was highly correlated (r = 0.8, P < .01) with
      silicosis. No abnormalities in heavy metal or trace minerals were detected. This
      evaluation indicated that horses with bone fragility disorder have systemic
      osteoporosis associated with fibrosing pulmonary silicosis. The etiopathogenesis
      of the bone fragility syndrome is unknown; however, this study provides
      circumstantial evidence for a silicate associated osteoporosis.

PMID- 21097717
TI  - Tamoxifen, flaxseed, and the lignan enterolactone increase stroma- and cancer
      cell-derived IL-1Ra and decrease tumor angiogenesis in estrogen-dependent breast
      cancer.
AB  - The proinflammatory cytokines IL-1alpha and IL-1beta promote tumor angiogenesis
      that might be counteracted by the IL-1 receptor antagonist (IL-1Ra), anakinra, a
      clinically approved agent. A diet with high amounts of phytoestrogens, such as
      flaxseed (Flax), genistein (GEN), and the mammalian lignan enterolactone (ENL),
      may affect breast cancer progression in a similar fashion as the antiestrogen
      tamoxifen. Both cancer cells and tumor stroma may be targets for cancer therapy.
      By using microdialysis in a model of human breast cancers in nude mice, we could
      perform species-specific analyses of released proteins in the microenvironment.
      We show that tumors treated with tamoxifen and fed Flax or ENL exhibited
      decreased in vivo release of IL-1beta derived from the murine stroma and
      decreased microvessel density whereas dietary GEN had no effects. Cancer cell
      released IL-1Ra were approximately 5 times higher than stroma-derived IL-1Ra.
      Tamoxifen, Flax, and ENL increased IL-1Ra levels significantly whereas GEN did
      not. The tumor stroma contained macrophages, which expressed the estrogen
      receptor. In vitro, estradiol decreased IL-1Ra released from breast cancer cells
      and from cultured macrophages. IL-1Ra decreased endothelial cell proliferation
      significantly in vitro whereas breast cancer cell proliferation was unaffected in
      presence of estradiol. Finally, IL-1Ra therapy of tumor-bearing mice opposed
      estrogen-dependent breast cancer growth and decreased angiogenesis. We conclude
      that the release of IL-1s both by cancer cells and the stroma, where macrophages
      are a key component, may offer feasible targets for antiestrogen therapy and
      dietary interventions against breast cancer.

PMID- 21097718
TI  - Genetic and structural variation in the gastric cancer kinome revealed through
      targeted deep sequencing.
AB  - Genetic alterations in kinases have been linked to multiple human pathologies. To
      explore the landscape of kinase genetic variation in gastric cancer (GC), we used
      targeted, paired-end deep sequencing to analyze 532 protein and phosphoinositide
      kinases in 14 GC cell lines. We identified 10,604 single-nucleotide variants
      (SNV) in kinase exons including greater than 300 novel nonsynonymous SNVs. Family
      wise analysis of the nonsynonymous SNVs revealed a significant enrichment in
      mitogen-activated protein kinase (MAPK)-related genes (P < 0.01), suggesting a
      preferential involvement of this kinase family in GC. A potential antioncogenic
      role for MAP2K4, a gene exhibiting recurrent alterations in 2 lines, was
      functionally supported by siRNA knockdown and overexpression studies in wild-type
      and MAP2K4 variant lines. The deep sequencing data also revealed novel, large
      scale structural rearrangement events involving kinases including gene fusions
      involving CDK12 and the ERBB2 receptor tyrosine kinase in MKN7 cells. Integrating
      SNVs and copy number alterations, we identified Hs746T as a cell line exhibiting
      both splice-site mutations and genomic amplification of MET, resulting in MET
      protein overexpression. When applied to primary GCs, we identified somatic
      mutations in 8 kinases, 4 of which were recurrently altered in both primary
      tumors and cell lines (MAP3K6, STK31, FER, and CDKL5). These results demonstrate
      that how targeted deep sequencing approaches can deliver unprecedented multilevel
      characterization of a medically and pharmacologically relevant gene family. The
      catalog of kinome genetic variants assembled here may broaden our knowledge on
      kinases and provide useful information on genetic alterations in GC.

PMID- 21097719
TI  - PDGFR signaling blockade in marrow stroma impairs lung cancer bone metastasis.
AB  - Bone microenvironment and cell-cell interactions are crucial for the initiation
      and development of metastasis. By means of a pharmacologic approach, using the
      multitargeted tyrosine kinase inhibitor sunitinib, we tested the relevance of the
      platelet-derived growth factor receptor (PDGFR) axis in the bone marrow (BM)
      stromal compartment for the initiation and development of lung cancer metastasis
      to bone. PDGFRbeta was found to be the main tyrosine kinase target of sunitinib
      expressed in BM stromal ST-2 and MC3T3-E1 preosteoblastic cells. In contrast, no
      expression of sunitinib-targeted receptors was found in A549M1 and low levels in
      H460M5 lung cancer metastatic cells. Incubation of ST-2 and human BM endothelial
      cells with sunitinib led to potent cell growth inhibition and induction of
      apoptosis in a dose-dependent manner. Similarly, sunitinib induced a robust
      proapoptotic effect in vivo on BM stromal PDGFRbeta(+) cells and produced
      extensive disruption of tissue architecture and vessel leakage in the BM cavity.
      Pretreatment of ST-2 cells with sunitinib also hindered heterotypic adhesion to
      lung cancer cell lines. These effects were correlated with changes in cell-cell
      and cell-matrix molecules in both stromal and tumor cells. Pretreatment of mice
      with sunitinib before intracardiac inoculation of A549M1 or H460M5 cells caused
      marked inhibition of tumor cells homing to bone, whereas no effect was found when
      tumor cells were pretreated before inoculation. Treatment with sunitinib
      dramatically increased overall survival and prevented tumor colonization but not
      bone lesions, whereas combination with zoledronic acid resulted in marked
      reduction of osteolytic lesions and osseous tumor burden. Thus, disruption of the
      PDGFR axis in the BM stroma alters heterotypic tumor-stromal and tumor-matrix
      interactions, thereby preventing efficient engagement required for bone homing
      and osseous colonization. These results support the notion that concomitant
      targeting of the tumor and stromal compartment is a more effective approach for
      blocking bone metastasis.

PMID- 21097720
TI  - The tipping point of animacy. How, when, and where we perceive life in a face.
AB  - Faces capture humans' attention; yet, beyond aesthetic appreciation, it is
      presumably not the face itself that interests people but the mind behind it.
      Minds think, feel, and act in ways that have direct consequences for well-being,
      but despite their importance, how minds are perceived in faces is not well
      understood. We investigated this mechanism by presenting participants with
      morphed images created from animate (human) and inanimate (mannequin) faces. Life
      and mind were perceived to "appear" at a consistent location on the morph
      continuum, close to the human endpoint. This location constituted a categorical
      boundary, as evidenced by increased sensitivity to differences in image pairs
      that straddled this tipping point. Additionally, the impression of life was
      gleaned from the eyes more than from other facial features. These results suggest
      that human beings are highly attuned to specific facial cues, carried largely in
      the eyes, that gate the categorical perception of life.

PMID- 21097721
TI  - Getting in under the radar. A dyadic view of invisible support.
AB  - There are many ways in which the provision of social support can be ineffective.
      Recent research suggests that the benefits of support may be maximized when it is
      provided invisibly. What remains unknown, however, is whether invisible support
      reflects the skillful behavior of support providers or recipients' blissful
      unawareness, as well as how invisible support is delivered during spontaneous
      social interactions. We hypothesized that both providers' skillful behavior and
      recipients' unawareness are necessary for invisible support to be effective, and
      we sought to document what effective invisible support looks like. Eighty-five
      couples engaged in a videotaped support interaction in the lab. Support
      recipients whose partners provided more invisible practical and emotional support
      (coded by observers) but who reported receiving less support experienced the
      largest preinteraction-to-postinteraction declines in negative emotions. In the
      case of practical invisible support, the combination of more support and less
      awareness of that support also predicted increases in self-efficacy. These
      results indicate that invisible support is a dyadic phenomenon.

PMID- 21097722
TI  - For whom is parting with possessions more painful? Cultural differences in the
      endowment effect.
AB  - The endowment effect--the tendency for owners (potential sellers) to value
      objects more than potential buyers do--is among the most widely studied judgment
      and decision-making phenomena. However, the current research is the first to
      explore whether the effect varies across cultures. Given previously demonstrated
      cultural differences in self-construals and self-enhancement, we predicted a
      smaller endowment effect for East Asians compared with Westerners. Two studies
      involving buyers and sellers of a coffee mug (Study 1a) and a box of chocolates
      (Study 1b) supported this prediction. Study 2 conceptually replicated this
      cultural difference by experimentally manipulating independent and interdependent
      self-construals. Finally, Study 3 provided evidence for an underlying self
      enhancement mechanism: Cultural differences emerged when self-object associations
      were made salient, but disappeared when self-object associations were minimized.
      Thus, the endowment effect may be influenced by the degree to which independence
      and self-enhancement (vs. interdependence and self-criticism) are culturally
      valued or normative.

PMID- 21097724
TI  - A tool to measure whether business management capacity in general practice
      impacts on the quality of chronic illness care.
AB  - Our aim was to develop a tool to identify specific features of the business and
      financial management of practices that facilitate better quality care for chronic
      illness in primary care. Domains of management were identified, resulting in the
      development of a structured interview tool that was administered in 97 primary
      care practices in Australia. Interview items were screened and subjected to
      factor analysis, subscales identified and the overall model fit determined. The
      instrument's validity was assessed against another measure of quality of care.
      Analysis provided a four-factor solution containing 21 items, which explained
      42.5% of the variance in the total scores. The factors related to administrative
      processes, human resources, marketing analysis and business development. All
      scores increased significantly with practice size. The business development
      subscale and total score were higher for rural practices. There was a significant
      correlation between the business development subscale and quality of care. The
      indicators of business and financial management in the final tool appear to be
      useful predictors of the quality of care. The instrument may help inform policy
      regarding the structure of general practice and implementation of a systems
      approach to chronic illness care. It can provide information to practices about
      areas for further development.

PMID- 21097725
TI  - Homogeneity of the German diagnosis-related groups.
AB  - This study analysed the outstanding homogeneity of the German Diagnosis-Related
      Groups (G-DRG) using the reduction in variance (R2) of costs. Arbitrary increase
      in case groups, definition of additional charges and combination of several case
      groups in one DRG were considered as potential confounders. In 2009, the G-DRG
      system offers an outstanding homogeneity with R2 of 83.5% in comparison to 2004
      with R2 of 70.2%. The effect of an arbitrary increase in case groups is
      negligible. However, a simulation of the other confounders explains three-fourth
      of the increase in R2 between 2004 and 2009. The definition of additional charges
      attributes in particular to the outstanding homogeneity. The assessment of DRG
      systems with R2 should be complemented with measures that are independent from a
      trimming of costs, e.g. relating actual costs with prospective payment. The G
      DRGs left medical ground in order to achieve optimal economical homogeneity.

PMID- 21097726
TI  - Strategic plan modelling by hospital senior administration to integrate diversity
      management.
AB  - Limited research suggests that some hospital senior administrators and chief
      executive officers (CEOs) have employed a strategic planning function to achieve
      diversity management practices. As the hospital industry struggles with how to
      integrate diversity practices to improve patient satisfaction, increase the
      quality of care and enhance clinical outcomes for minority populations,
      understanding the planning process involved in this endeavour becomes significant
      for senior hospital administrators. What is not well understood is what this
      strategic planning process represents and how it is applied to integrate
      diversity management. Scant research exists about the type of strategic models
      that hospital CEOs employ when they wish to reposition their organizations
      through diversity management. This study examines the strategic planning models
      used by senior administrators to integrate diversity management for an
      institutional-wide agenda. A qualitative survey process was used for CEOs in the
      states of New York, Pennsylvania, New Jersey and Delaware. The key research
      questions dealt with what type of strategic plan approach senior administrators
      used for integrating diversity management and what rationale they used to pursue
      this. Significant differences were reported between three types of strategic plan
      modelling used by CEOs. Also, when comparing past and current practices over
      time, such differences existed. The need to integrate diversity management is
      underscored by this study. How senior hospital administrators apply strategic
      plan models and what impact these approaches have represent the major
      implications that this study offers.

PMID- 21097727
TI  - Increased access rate to a primary health-care centre by introducing a structured
      patient sorting system developed to make the most efficient use of the personnel:
      a pilot study.
AB  - The primary health-care centre (PHCC) participating in the study has had
      financial problems for several years and it has been particularly difficult to
      recruit general practitioners (GPs). As a result, the access rate to the PHCC was
      low. The purpose of this study was to increase the access rate to the PHCC and to
      make the most efficient use of the staff by introducing a structured patient
      sorting system. All personnel were involved in the implementation process and
      participated regularly in interdisciplinary work-groups. A variety of Drop-in
      receptions were created and a manual for sorting patients by condition was
      introduced. The main finding was that the total access rate to the PHCC increased
      by 27% and that each staff member increased their personal access rate by an
      average of 13%. Eighty-three percent of the patients who were initially treated
      by the rehabilitation team were treated solely by the team and did not need to
      see a GP. No medical backlashes were reported. These findings indicate a more
      efficient use of the personnel. Furthermore, both personnel and patients
      indicated an improvement in the possibility to book patient appointments after
      the introduction of the structured patient sorting system.

PMID- 21097728
TI  - The rise of governmentality in the Italian National Health System: physiology or
      pathology of a decentralized and (ongoing) federalist system?
AB  - In this paper, we aim to discuss the implications and lessons that can be learnt
      from the ongoing process of federalism affecting the Italian National Health
      System (INHS). Many countries are currently taking decisions concerning the
      decentralization or re-centralization of their health-care systems, with several
      key issues that are illustrated in the recent history of the INHS. The
      decentralization process of INHS has produced mixed results, as some regions took
      advantage of it to strengthen their systems, whereas others were not capable of
      developing an effective steering role. We argue that the mutual reinforcement of
      the decentralization and recentralization processes is not paradoxical, but is
      actually an effective way for the State to maintain control over the equity and
      efficiency of its health-care system while decentralizing at a regional level. In
      this perspective, we provide evidence backing up some of the assumptions made in
      previous works as well as new food-for thought - specifically on how
      governmentality and federalism should meet - to reshape the debate on
      decentralization in health care.

PMID- 21097729
TI  - The empowerment and quality health value propositions of e-health.
AB  - E-health, as well as its value and benefits, has been characterized as a concept
      defined in various ways depending on intended audience and use. Attempts to
      define, characterize and appreciate e-health inadvertently portray it as
      something out of main stream academia; thus, undermining the relevance and
      importance of the transformation capabilities of e-health on the practice of
      health care from the individual and organizational perspectives. In order to
      contribute towards an understanding and appreciation of e-health as a main stream
      concept, we propose the use of existing models, theories and principles in
      support of e-health. Specifically, the empowerment theory and the principles of
      quality health will be used to discuss the value proposition of e-health. An
      understanding of the e-health value proposition is important, because it helps
      organizations to develop a shared vision and context, which in turn keeps
      organizations focused and realistic as they expend resources and adopt e-health.
      It also helps e-health consumers understand what is possible and impossible, and
      how they can best participate in e-health for the betterment of their health and
      health care.

PMID- 21097730
TI  - The effect of work environment on intent to leave the nursing profession: a case
      study of bedside registered nurses in rural Florida.
AB  - The purpose of this research was to explore the effect work environment has on
      the intent to leave the profession for rural hospital bedside registered nurses
      (RNs). Subscales of autonomy, control over the practice setting, nurse-physician
      relationship and organizational support were incorporated into the analysis to
      determine which aspects of work environment directly affect the intent to leave
      the profession. An explanatory cross-sectional survey was distributed to 259
      direct care bedside RNs employed at a rural system-affiliated hospital in Central
      Florida between February 2007 and June 2007. Anonymity was assured. A
      questionnaire containing demographic questions, the Nursing Work Index-Revised
      and Blau's intent to leave scale was distributed to all direct care nurses. A
      32.8% response rate was achieved for a total of 85 complete and usable surveys.
      Data analysis shows that the work environment in general is negatively related to
      intent to leave. In addition, each of the four subscales was also negatively
      related to the intent to leave the profession. The results of this study support
      several recommendations for practice and education, including the promotion of
      professional practice environments, fostering inter-departmental relationships,
      and increasing the managerial training of RN managers.

PMID- 21097731
TI  - European guideline for the management of donovanosis, 2010.
AB  - Donovanosis is a rare sexually transmitted infection now mainly seen in sporadic
      cases in Papua New Guinea, South Africa, India, Brazil and Australia. The
      causative organism is Calymmatobacterium granulomatis though a proposal has been
      put forward that the organism be reclassified as Klebsiella granulomatis comb.
      nov. The incubation period is approximately 50 days with genital papules
      developing into ulcers that increase in size. Four types of lesions are described
      - ulcerogranulomatous, hypertrophic, necrotic and sclerotic. The diagnosis is
      usually confirmed by microscopic identification of characteristic Donovan bodies
      on stained tissue smears. More recently, polymerase chain reaction (PCR) methods
      have been developed. The recommended treatment is azithromycin 1 g weekly until
      complete healing is achieved.

PMID- 21097732
TI  - Sensitivity and specificity of herpes simplex virus-2 serological assays among
      HIV-infected and uninfected urban Ugandans.
AB  - Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV-1 infection. We
      characterized HSV-2 serology assay performance in HIV-positive and HIV-negative
      Africans. Serostatus for HSV-2 and HIV-1 was determined in 493 serum specimens
      stored from a community HSV-2 prevalence survey in Kampala, Uganda. HSV-2
      serology by Focus HerpeSelect ELISA, Biokit HSV-2 rapid assay and Kalon HSV-2 was
      compared with HSV-2 Western blot (WB) according to HIV-1 serostatus.
      Sensitivity/specificity was: 99.5%/70.2% for Focus, 97.0%/86.4% for Biokit and
      97.5%/96.2% for Kalon. Focus with Biokit confirmation improved
      sensitivity/specificity (99.4%/96.8%, respectively). Use of a higher Focus index
      value cut-off of 2.2 instead of 1.1 increased specificity from 70.2% to 92.4%.
      Kalon had higher specificity than Focus (P < 0.001). Of commercially available
      HSV-2 serological assays, Kalon alone, or Focus ELISA followed by Biokit
      confirmation perform best. Improved HSV-2 assays are needed for HSV-2 and HIV-1
      public health activities in Africa.

PMID- 21097733
TI  - HIV non-occupational postexposure prophylaxis in a Canadian province: treatment
      completion and follow-up testing.
AB  - Provincial guidelines for HIV non-occupational postexposure prophylaxis (NPEP)
      were implemented on January 2005 in Alberta, Canada. Human immunodeficiency virus
      (HIV) NPEP was provided free of charge following approval by a medical officer of
      health. Between 1 January 2005 and 30 June 2007, 174 individuals were prescribed
      NPEP; 135 (78%) were women with a median age of 24 years. Sexual assaults
      accounted for 68% of exposures. NPEP was completed in 49% of cases. Individuals
      who completed NPEP were less likely to have been exposed by sexual assault (P =
      0.04) and more likely to have received HIV follow-up testing (P =
      0.03).Individuals who received at least one HIV follow-up test were older (P =
      0.03) and more likely to have been exposed percutaneously (P = 0.003). Those who
      received no follow-up testing were less likely to have filled an NPEP
      prescription (P = 0.0001). New strategies are required to improve follow-up of
      individuals receiving NPEP, especially younger persons or sexual assault
      survivors.

PMID- 21097734
TI  - Effects on condom use of an HIV prevention programme 36 months postintervention:
      a cluster randomized controlled trial among Bahamian youth.
AB  - Data are lacking on long-term effects of HIV behavioural intervention programmes.
      In this study, we report intervention effects 36 months postintervention on
      condom use and relevant outcome variables from the theory-based programme 'Focus
      on Youth in the Caribbean' (FOYC). Participants (1360 sixth-grade youth) were
      randomized by school into: (1) FOYC, plus one of two brief parent interventions
      or (2) the control condition 'Wondrous Wetlands', plus a brief parent
      intervention. Mixed effect analysis demonstrated significant programme effects,
      including enhanced HIV/AIDS knowledge (effect size D = 0.44, 95% confidence
      interval [CI]: 0.43, 0.46), increased self-efficacy of (D = 0.42, 95% CI: 0.30,
      0.54), skills for (D = 0.62, 95% CI: 0.56, 0.64) and intention to use a condom (D
      = 0.20, 95% CI: 0.03, 0.37). Youth who received FOYC plus the parental monitoring
      intervention had higher condom use rates (odds ratio = 1.49, 95% CI: 0.97, 2.28).
      Feedback effects from key variables were also detected, supporting the sustained
      effect.

PMID- 21097735
TI  - High prevalence of HIV-1, HIV-2 and other sexually transmitted infections among
      women attending two sexual health clinics in Bissau, Guinea-Bissau, West Africa.
AB  - The objective was to examine the prevalence of HIV-1, HIV-2 and 10 other sexually
      transmitted infections (STIs), and to explore the relationship between HIV and
      those STIs in women attending two sexual health clinics in Bissau, Guinea-Bissau.
      In all, 711 women with urogenital problems were included. Clinical examination
      was performed and HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-1, HTLV-2
      and syphilis were diagnosed by serology. Trichomonas vaginalis was examined using
      wet mount microscopy. Cervical samples (and swabs from visible ulcers, if
      present) were used for polymerase chain reaction (PCR) diagnosis of Chlamydia
      trachomatis, Mycoplasma genitalium, Haemophilus ducreyi, herpes simplex virus
      (HSV)-1 and HSV-2, and culture diagnosis of Neisseria gonorrhoeae. The prevalence
      of HIV-1, HIV-2, and HIV-1 and HIV-2 (dual infection) was 9.5%, 1.8% and 1.1%,
      respectively. The prevalence of HTLV-1 was 2.8%, HTLV-2 0%, HSV-1 1.4%, HSV-2
      7.7%, T. vaginalis 20.4%, syphilis 1.0%, N. gonorrhoeae 1.3%, H. ducreyi 2.7%, M.
      genitalium 7.7% and C. trachomatis 12.6%. HIV-1 and/or HIV-2 infection was
      significantly associated with active HSV-2 and HIV-1 was significantly associated
      with M. genitalium infection. In conclusion, HIV-1 and HIV-2 prevalence was
      higher compared with previous studies of pregnant women in Guinea-Bissau. The
      prevalence of co-infection of HIV and other STIs is high. National evidence-based
      guidelines for the management of STIs in Guinea-Bissau are essential.

PMID- 21097736
TI  - The awareness of postexposure prophylaxis for HIV infection following sexual
      exposure in emergency departments in a regional HIV network.
AB  - The introduction of UK clinical guidelines in 2006 set clear standards for the
      provision of postexposure prophylaxis for HIV following sexual exposure (PEPSE)
      to patients who present to health-care settings. However, some patients have
      reported wide inequities in provision of PEPSE. We used a questionnaire to
      evaluate staff awareness and provision of PEPSE in various clinical situations in
      three major emergency departments (EDs) in the Wessex region of the UK. Thirty
      three doctors and 50 nurses completed the questionnaire. There was a general lack
      of awareness regarding local protocols, availability of postexposure prophylaxis
      (PEP) packs and whom to contact for advice. Knowledge about PEP provision varied
      according to clinical scenario but was better among senior medical staff. The
      deficits in awareness and knowledge of PEPSE among ED staff highlighted in this
      study raises concerns about patients' access to this intervention. We plan to
      implement local training to address these issues and raise awareness of the local
      genitourinary medicine/HIV services as a source of advice.

PMID- 21097737
TI  - A survey of sexual health services in UK prisons.
AB  - Sexual health services in prisons are provided without recognized national
      standards or commissioning guidance and surveillance data are incomplete. This
      original survey provides essential information on key elements of services in a
      large sample of UK prisons that will inform planning, development and monitoring
      of such services in an era of scarce NHS resources.

PMID- 21097738
TI  - A comparison of sexual and reproductive health services provided by genitourinary
      and family planning clinics for adolescents.
AB  - The purpose of the study was to assess the use of sexual and reproductive health
      services by adolescents aged 15 years and younger. A case-note review was
      conducted at both a genitourinary medicine clinic and a family planning clinic in
      Edinburgh, UK. The demographics of the attendees, reasons for attending, risk
      factors, diagnostic tests undertaken and contraceptive advice given differed
      between the two clinics. Approximately 73% of attendees with documented responses
      used alcohol and 21% used recreational drugs, 5% reported self-harm, 25% reported
      being victims of sexual assault, 13% had a current sexually transmitted infection
      and 6% of girls had already been pregnant. While this group of young people
      understand the differences in emphasis between the clinics, adolescents may be
      intimidated and discouraged from attending or may fail to return, and the
      combination of overlap, together with omissions in cross-clinic function,
      suggests that for this age group the services of these clinics should be
      combined.

PMID- 21097739
TI  - Completion of a British Association for Sexual Health and HIV regional audit
      loop: HIV testing in genitourinary medicine clinics in Scotland in 2004 and 2008.
AB  - In 2004, the British Association for Sexual Health and HIV Scottish Branch
      audited HIV testing in new attendees diagnosed with a sexually transmitted
      infection at genitourinary medicine clinics in Scotland. In 2008 the audit loop
      was completed. Large increases were seen in rates of test offer and uptake,
      particularly in health boards with low baseline levels of testing. Overall rates
      of testing remain below those recommended and wide variability between boards
      persists.

PMID- 21097740
TI  - Distribution and characteristics of sexual health service provision in primary
      and community care in England.
AB  - The objective of this paper was to identify and describe enhanced sexual health
      services (ESHSs) commissioned for testing, diagnosis and management of sexually
      transmitted infections (STIs) in primary and community care settings in England.
      ESHSs commissioned by Primary Care Trusts (PCTs) in England were determined by
      telephone survey. Further information on service provision was collected by a
      follow-up email survey. By April 2009, 464 ESHSs had been commissioned to offer
      testing, diagnosis and treatment of STIs. Most providers were enhanced general
      practices (56%). Two in five PCTs did not offer any ESHSs and five PCTs had
      neither genitourinary medicine services nor ESHSs. Among 52 ESHSs that responded,
      screening and partner notification strategies varied. The distribution and
      characteristics of ESHS provision in England are heterogeneous emphasizing the
      need to establish clear clinical care pathways between services. Routine
      reporting and analysis of service activity could help ensure provision meets
      local needs.

PMID- 21097741
TI  - Gardnerella vaginalis septicaemia with pyelonephritis, infective endocarditis and
      septic emboli in the kidney and brain of an adult male.
AB  - Gardnerella vaginalis is typically associated with bacterial vaginosis in women.
      However, balanitis, urethritis, urinary tract infections and asymptomatic
      bacteraemia have also been described in men. Here we report a case of G.
      vaginalis septicaemia with infective endocarditis and septic emboli in the kidney
      and brain of an adult male.

PMID- 21097742
TI  - A cured patient who came back for consultation: neuropathic scrotal pruritus
      relieved after ipsilateral inguinal hernia repair.
AB  - When no demonstrable cause is uncovered after excluding inflammatory dermatosis,
      infectious disease or a manifestation of anorectal disease, anogenital pruritus
      is often described as 'idiopathic'. Lumbosacral radiculopathy was described by
      Cohen et al. as one of the possible causes of 'idiopathic' anogenital pruritus.
      We report a case of a patient with chronic pruritus of the right scrotum that was
      relieved immediately post-ipsilateral inguinal hernia repair. This is, to the
      best of our knowledge, the first case of neuropathic scrotal pruritus secondary
      to direct nerve compression by an inguinal hernia. We propose that a proper
      examination for the presence of inguinal hernia be performed in the work-up for
      scrotal pruritus.

PMID- 21097743
TI  - A case of sexual transmission of Escherichia coli leading to urine infections in
      a male homosexual couple?
AB  - We report a case of simultaneous identical Escherichia coli urinary tract
      infections in a male homosexual couple practising unprotected insertive anal
      intercourse, and propose sexual transmission between the couple.

PMID- 21097744
TI  - BCG-itis in two antiretroviral-treated HIV-infected infants.
AB  - Although vaccination with Bacille Calmette-Guerin (BCG) is considered safe,
      adverse regional (BCG-itis) and disseminated (BCG-osis) diseases preferentially
      occur in the immunocompromised host. The infection with human immunodeficiency
      virus (HIV) by mother-to-child transmission leads to impaired cellular immune
      responses, a situation that poses a great challenge regarding the universal use
      of BCG vaccine. World Health Organization recommends that children who are known
      to be HIV-infected, even if asymptomatic, should no longer be immunized with BCG.
      Many of the complications of BCG vaccination occur in severely immunosuppressed
      HIV-infected children and are related to late institution of antiretroviral and
      antimycobacterial therapy. We report two cases of BCG-itis in HIV-infected
      infants, who fulfilled clinical criteria of immune reconstitution inflammatory
      syndrome: axillary adenitis, one with suppuration, and both temporally associated
      with precocious restoration of immunity elicited by the use of antiretroviral
      therapy. Isoniazid (10 mg/kg/day) was offered until regression of adenopathies,
      and lesions were not handled.

PMID- 21097745
TI  - Trichomonas vaginalis: an unusual presentation.
AB  - We report a case of Trichomonas vaginalis (TV) presenting as vulval ulceration in
      a 41-year-old woman. There was complete resolution of her symptoms only after
      oral tinidazole. The delayed diagnosis and importance of using the correct tests
      for the diagnosis of TV are discussed.

PMID- 21097746
TI  - Saturday service: one year on.

PMID- 21097747
TI  - Reply: still crazy, but now has antisocial behaviour order.

PMID- 21097748
TI  - Reply: something for the weekend!

PMID- 21097749
TI  - Analysis of quality of proxy questions in health surveys by behavior coding.
AB  - The aim of this study is to show how to analyze the quality of questions for
      proxy informants by means of behavior coding. Proxy questions can undermine
      survey data quality because of the fact that proxies respond to questions on
      behalf of other people. Behavior coding can improve questions by analyzing
      interviewer-respondent interactions. Twenty-nine proxies participated in the
      pretesting of a disability questionnaire. The questionnaire includes 11 questions
      related to daily-life limitations as a result of health problems. Interviewer
      proxy interactions were coded and analyzed by means of Sequence Viewer program.
      The percentages, from a methodological perspective, of ideal "question-and
      answer" sequences varied from 28% to 76% throughout the 11 questions analyzed.
      The results obtained pointed out the necessity of reviewing some of the proxy
      questions analyzed. Behavior coding can improve the quality of proxy questions in
      health surveys when proxy informants are surveyed.

PMID- 21097750
TI  - Consequences of AhR activation in steady-state dendritic cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototypical aryl hydrocarbon
      receptor (AhR) ligand and a potent immunotoxicant. However, the mechanisms
      underlying TCDD-induced immunomodulation remain to be defined. Dendritic cells
      are professional antigen-presenting cells that constitutively express the AhR and
      are sensitive to TCDD-induced AhR activation. We hypothesized that AhR activation
      alters the differentiation and function of steady-state bone marrow-derived
      dendritic cells (BMDCs). To test this hypothesis, steady-state BMDCs from C57BL/6
      mice were grown in the presence of TCDD or vehicle. TCDD-treated steady-state
      BMDCs (TCDD-BMDCs) displayed decreased expression of CD11c and CD11a, whereas
      increasing the frequency of major histocompatibility complex class II, CD86,
      CD80, and CD54. Similar phenotypic alterations were observed with the AhR ligands
      6-formylindolo[3,2-b]carbazole and 2-(1H-indole-3'-carbonyl)-thiazole-4
      carboxylic acid (ITE). TCDD-BMDCs from AhR(-/-) mice were refractory to TCDD
      induced surface marker alterations, whereas TCDD-BMDCs from AhR(dbd/dbd) mice
      displayed similar phenotypic alterations as AhR(+/+) TCDD-BMDCs. Following
      lipopolysaccharide (LPS), cytosine-phosphate-guanine (CpG), or Imiquimod
      stimulation, TCDD-BMDCs secreted less interleukin (IL)-6, tumor necrosis factor
      alpha (TNF-alpha), IL-10, and IL-12. TCDD also altered NF-kappaB family member
      binding activity in unstimulated and LPS- or CpG-stimulated steady-state BMDCs.
      The internalization of the soluble antigens, ovalbumin, and acetylated low
      density lipoprotein was decreased, whereas internalization of latex beads was
      increased in TCDD-BMDCs when compared with vehicle-BMDCs. TCDD-BMDCs displayed
      increased messenger RNA expression of the regulatory gene IDO2 and following LPS
      stimulation upregulated IDO1, IDO2, TGFbeta1, and TGFbeta3 gene expression.
      Additionally, TCDD-BMDCs increased the generation of CD4(+) CD25(+) FoxP3(+)
      Tregs in vitro in an IDO-dependent fashion. However, TCDD-treated BMDCs did not
      alter antigen-specific T-cell activation in vivo. Overall, TCDD-induced AhR
      activation alters the differentiation, activation, innate, and immunoregulatory
      function but not the T cell-activating capacity of steady-state BMDCs.

PMID- 21097751
TI  - Letter to the editor.

PMID- 21097753
TI  - The broader picture on guideline adherence.

PMID- 21097754
TI  - Guidelines for nutrition in the critically ill: are we altogether or in-the
      altogether?

PMID- 21097755
TI  - Efficacy vs effectiveness.

PMID- 21097756
TI  - What's better?

PMID- 21097757
TI  - Guidelines and practice: the need to determine compliance.

PMID- 21097758
TI  - A difference must make a difference.

PMID- 21097759
TI  - Analyzing ICU physician and dietitian adherence to nutrition therapy guidelines.

PMID- 21097760
TI  - Nutrition trials in critical illness: bigger, faster, stronger.

PMID- 21097761
TI  - Lost in (knowledge) translation!
AB  - Critical care nutrition guidelines have been developed to help busy practitioners
      decide how to feed their critically ill patients. However, despite the
      publication of guidelines and efforts to disseminate and implement them, there
      are large gaps between what the recommendations say and what is happening at the
      bedside. Consequently, the nutrition therapy received by many patients remains
      suboptimal. Knowledge translation is a term increasingly used in healthcare to
      describe the process of moving evidence learned from clinical research and
      summarized in clinical practice guidelines to incorporation into clinical and
      policy decision making. In this article, knowledge about the implementation of
      critical care nutrition guidelines is applied to Graham et al's knowledge-to
      action model to illuminate the issues pertinent to knowledge translation in
      critical care nutrition. This model has 2 components: knowledge creation and
      action. The action component consists of 8 phases of the action cycle that
      represent activities needed to move knowledge into practice and are derived from
      planned-action theory. Components of this model are illustrated via empirically
      derived research, commentaries, and published studies from the field of critical
      care nutrition. It is hoped that this article and related articles in this issue
      of JPEN will help critical care nutrition practitioners to better understand the
      often complex and convoluted road of translating knowledge into practice so that
      as a community we are no longer "lost" but have direction that can bring about
      positive changes in nutrition practice.

PMID- 21097762
TI  - Understanding adherence to guidelines in the intensive care unit: development of
      a comprehensive framework.
AB  - BACKGROUND: Clinical practice guidelines (CPGs) have been hailed as a useful
      method of translating evidence into practice. Several CPGs have been published
      that provide recommendations for feeding patients in the intensive care unit
      (ICU). Despite a rigorous development process and active dissemination of these
      guidelines, their impact on nutrition practice has been modest. The purpose of
      this study was to develop a comprehensive framework for understanding adherence
      to nutrition CPGs in the critical care setting. METHODS: Multiple case studies
      were completed at 4 Canadian ICUs. Semistructured interviews were conducted with
      7 key informants at each ICU site who were asked about their perceptions and
      attitudes toward guidelines in general and the Canadian Critical Care Nutrition
      CPGs specifically. Interview transcripts and related documents were analyzed
      qualitatively using a framework approach. RESULTS: The 5 key components of the
      developed framework were characteristics of the CPGs, the implementation process,
      institutional factors, provider intent, and the clinical condition of the
      patient. These key themes encapsulate numerous itemized factors that contribute
      to guideline adherence either as barriers or enablers. CONCLUSIONS: Adherence to
      nutrition CPGs is determined by a complex interaction of multiple factors that
      act as barriers or enablers. The comprehensive framework for adherence to CPGs in
      the ICU attempts to elucidate this process and provides a useful template for
      future research. Future quality improvement initiatives should assess local
      barriers to change and design interventions to overcome these barriers.

PMID- 21097763
TI  - Guidelines, guidelines, guidelines: what are we to do with all of these North
      American guidelines?
AB  - Over the past decade, clinical guidelines for nutrition therapy in the critically
      ill have been developed by different North American societies. To avoid target
      audience confusion and uncertainty, there is a need to undergo a review of the
      content of these guidelines. In this review, the authors compared the grading
      systems, the levels of evidence used, and the content of North American nutrition
      clinical guidelines. The 3 clinical guidelines that met their search criteria and
      hence were included in the comparison are the Canadian Clinical Practice
      Guidelines, the American Dietetics Association's evidence-based guideline for
      critical illness, and the Society of Critical Care Medicine and American Society
      of Parenteral and Enteral Nutrition's joint guideline. Through their comparison,
      the authors have shown that although there are several topics where there is a
      similar direction of recommendation across the 3 societies/organizations, there
      are stark contrasts among many of the recommendations. These major differences
      can be attributed to the admission of different populations, lower levels of
      evidence or expert opinion into the guideline production process, lack of clarity
      in the link between the evidence and the recommendation, and lack of uniformity
      in the reporting of levels of evidence and grades of recommendation. The authors
      have identified the need for the North American nutrition organizations to
      harmonize the development of future nutrition guidelines in a timely way, so that
      they remain current and up-to-date. Furthermore, guideline users need to be aware
      of the dissimilarities in these guidelines before applying the recommendations to
      their daily practice.

PMID- 21097764
TI  - Nutrition therapy for the critically ill surgical patient: we need to do better!
AB  - BACKGROUND: To identify opportunities for quality improvement, the nutrition
      adequacy of critically ill surgical patients, in contrast to medical patients, is
      described. METHODS: International, prospective, and observational studies
      conducted in 2007 and 2008 in 269 intensive care units (ICUs) were combined for
      purposes of this analysis. Sites provided institutional and patient
      characteristics and nutrition data from ICU admission to ICU discharge for
      maximum of 12 days. Medical and surgical patients staying in ICU at least 3 days
      were compared. RESULTS: A total of 5497 mechanically ventilated adult patients
      were enrolled; 37.7% had surgical ICU admission diagnosis. Surgical patients were
      less likely to receive enteral nutrition (EN) (54.6% vs 77.8%) and more likely to
      receive parenteral nutrition (PN) (13.9% vs 4.4%) (P < .0001). Among patients
      initiating EN in ICU, surgical patients started EN 21.0 hours later on average
      (57.8 vs 36.8 hours, P < .0001). Consequently, surgical patients received less of
      their prescribed calories from EN (33.4% vs 49.6%, P < .0001) or from all
      nutrition sources (45.8% vs 56.1%, P < .0001). These differences remained after
      adjustment for patient and site characteristics. Patients undergoing
      cardiovascular and gastrointestinal surgery were more likely to use PN, were less
      likely to use EN, started EN later, and had lower total nutrition and EN adequacy
      rates compared with other surgical patients. Use of feeding and/or glycemic
      control protocols was associated with increased nutrition adequacy. CONCLUSIONS:
      Surgical patients receive less nutrition than medical patients. Cardiovascular
      and gastrointestinal surgery patients are at highest risk of iatrogenic
      malnutrition. Strategies to improve nutrition performance, including use of
      protocols, are needed.

PMID- 21097765
TI  - Bridging the guideline-practice gap in critical care nutrition: a review of
      guideline implementation studies.
AB  - Several clinical practice guidelines focusing on nutrition therapy in
      mechanically ventilated, critically ill patients are available to assist busy
      critical care practitioners in making decisions regarding feeding their patients.
      However, large gaps have been observed between guideline recommendations and
      actual practice. To be effective in optimizing nutrition practice, guideline
      development must be followed by systematic guideline implementation strategies.
      Systematic reviews of studies evaluating guideline implementation interventions
      outside the critical care setting found that these strategies, such as reminders,
      educational outreach, and audit and feedback, produce modest to moderate
      improvements in processes of care, with considerable variation observed both
      within and across studies. Unfortunately, the optimal strategies to implement
      guidelines in the intensive care unit are poorly understood, with scarce data
      available to guide our decisions on which strategies to use. The authors
      identified 3 cluster randomized trials evaluating the implementation of nutrition
      guidelines in the critical care setting. These studies demonstrated small
      improvements in nutrition practice, but no significant effect on patient
      outcomes. There are some data to suggest that tailoring guideline implementation
      strategies to overcome identified barriers to change might be a more effective
      approach than the multifaceted "one size fits all" strategy used in previous
      studies. Adopting this tailored approach to guideline implementation in future
      studies may help bridge the current guideline-practice gap and lead to
      significant improvements in nutrition practices and patient outcomes.

PMID- 21097766
TI  - The value of audit and feedback reports in improving nutrition therapy in the
      intensive care unit: a multicenter observational study.
AB  - BACKGROUND: The objective of this study was to determine whether auditing
      practice and providing feedback in the form of benchmarked site reports is an
      effective strategy to improve adherence to nutrition guidelines. METHODS: The
      authors conducted a multicenter observational study in Canadian intensive care
      units (ICUs). In January 2007, an audit of daily nutrition information was
      collected (type and amount of nutrition received and strategies to improve
      nutrition delivery). Each ICU was e-mailed individualized benchmarked performance
      reports documenting their performance compared with the Canadian Critical Care
      Nutrition guidelines and in relation to the other ICUs. Nutrition practice was
      reaudited in May 2008 to evaluate changes in practice. RESULTS: Twenty-six ICUs
      in Canada participated, with 473 and 486 patients accrued in 2007 and 2008,
      respectively. The authors observed a significant increase in enteral nutrition
      (EN) adequacy (from 45.1% to 51.9% for calories, and from 44.8% to 51.5% for
      protein) and an increase in the percentage of patients receiving EN without
      parenteral nutrition (from 71.9% to 81.3%). They also observed trends toward
      improvements in the percentage of patients who had EN started within 48 hours
      (from 60.3% to 66.8%). There were no significant differences in the use of
      motility agents or small bowel feeding in patients who had high gastric residual
      volumes. CONCLUSION: Audit and feedback reports are associated with improvement
      in some nutrition practices in many ICUs; however, the magnitude of these effects
      is quite modest. More research is needed to determine the optimal methods of
      using audit and feedback to improve quality of nutrition care.

PMID- 21097767
TI  - The relationship between organizational culture and implementation of clinical
      practice guidelines: a narrative review.
AB  - The context in which critical care providers work has been shown to be associated
      with adherence to recommendations of clinical practice guidelines (CPGs).
      Consideration of contextual factors such as organizational culture may therefore
      be important when implementing guidelines. Organizational culture has been
      defined simply as "how things are around here" and encompasses leadership,
      communication, teamwork, conflict resolution, and other domains. This narrative
      review highlights the results of recent quantitative and qualitative studies,
      including studies on adherence to nutrition guidelines in the critical care
      setting, which demonstrate that elements of organizational culture, such as
      leadership support, interprofessional collaboration, and shared beliefs about the
      utility of guidelines, influence adherence to guideline recommendations. Outside
      nutrition therapy, there is emerging evidence that strategies focusing on
      organizational change (eg, revision of professional roles, interdisciplinary
      teams, integrated care delivery, computer systems, and continuous quality
      improvement) can favorably influence professional performance and patient
      outcomes. Consequently, future interventions aimed at implementing nutrition
      guidelines should aim to measure and take into account organizational culture, in
      addition to considering the characteristics of the patient, provider, and
      guideline. Further high quality, multimethod studies are required to improve our
      understanding of how culture influences guideline implementation, and which
      organizational change strategies might be most effective in optimizing nutrition
      therapy.

PMID- 21097768
TI  - Impact of enteral feeding protocols on enteral nutrition delivery: results of a
      multicenter observational study.
AB  - BACKGROUND: To evaluate the effect of enteral feeding protocols on key indicators
      of enteral nutrition in the critical care setting. METHODS: International,
      prospective, observational, cohort studies conducted in 2007 and 2008 in 269
      intensive care units (ICUs) in 28 countries were combined for the purposes of
      this analysis. The study included 5497 consecutively enrolled, mechanically
      ventilated, adult patients who stayed in the ICU for at least 3 days. Sites
      recorded the presence or absence of a feeding protocol operational in their ICU.
      They provided selected nutritional data on enrolled patients from ICU admission
      to ICU discharge for a maximum of 12 days. Sites that used a feeding protocol
      were compared with those that did not. RESULTS: On average, protocolized sites
      used more enteral nutrition (EN) alone (70.4% of patients vs 63.6%, P = .0036),
      started EN earlier (41.2 hours from admission to ICU vs 57.1, P = .0003), and
      used more motility agents in patients with high gastric residual volumes (64.3%
      of patients vs 49.0%, P = .0028) compared with sites that did not use a feeding
      protocol. Overall nutritional adequacy (61.2% of patients' caloric requirements
      vs 51.7%, P = .0003) and adequacy from EN were higher in protocolized sites
      compared with nonprotocolized sites (45.4% of requirements vs 34.7%, P < .0001).
      EN adequacy remained significantly higher after adjustment for pertinent patient
      and ICU level baseline characteristics. CONCLUSIONS: The presence of an enteral
      feeding protocol is associated with significant improvements in nutrition
      practice compared with sites that do not use such a protocol.

PMID- 21097769
TI  - Attitudes and beliefs related to the Canadian critical care nutrition practice
      guidelines: an international survey of critical care physicians and dietitians.
AB  - BACKGROUND: The objective of this study was to evaluate the attitudes of critical
      care practitioners toward the Canadian Critical Care Nutrition Clinical Practice
      Guidelines (CPGs) and compare them with actual practice. METHODS: An
      international Web-based survey was conducted. Respondents were asked to rate
      their strength of recommendation for 26 nutrition practices included in the
      Canadian CPGs. Attitudinal results were compared with actual practice on each
      recommendation. RESULTS: 514 practitioners from 27 countries completed the
      survey. The majority (91.4%) considered nutrition therapy to be very important
      for critically ill patients. There was strong endorsement for the following
      established practices: enteral nutrition (EN) used in preference to parenteral
      nutrition (PN), use of polymeric solutions and feeding protocols, and avoiding
      hyperglycemia. There was also strong endorsement for the following practices that
      are not routinely done in actual practice: EN initiated within 24 to 48 hours of
      admission, use of motility agents, head-of-bed elevation, use of glutamine and
      antioxidants, and maximizing EN before starting PN. There was diversity of
      opinion on the recommendations pertaining to arginine-supplemented diets, small
      bowel feeding, use of pharmaconutrients, intensive insulin therapy, and
      withholding soybean oil lipids in PN solutions and hypocaloric PN. CONCLUSIONS:
      Overall, attitudes toward the Canadian CPGs were positive. However, we identified
      some areas where there was diversity of opinion, highlighting a need for further
      research and education. System tools may be a useful strategy to integrate
      guideline recommendations into practice where there is strong endorsement but the
      recommendation is not happening in actual practice.

PMID- 21097770
TI  - Randomized trials in critical care nutrition: look how far we've come! (and where
      do we go from here?).
AB  - BACKGROUND: The purpose of this methodological review is to quantify and qualify
      critical care nutrition randomized controlled trials (RCTs) that inform our
      practice, to evaluate their strengths and limitations, and to recommend
      strategies for improving the design of future trials in this area. METHODS: The
      literature was systematically reviewed to find all RCTs published between 1980
      and December 2008 that evaluated nutrition interventions in critical care. Data
      were abstracted on the nature and quality of included RCTs. RESULTS: A total of
      207 RCTs met the inclusion criteria. Of these, 170 (82.1%) were single-center,
      and 37 (17.9%) were multicenter. The largest number of trials evaluated intensive
      insulin therapy (n = 25), arginine-supplemented diets (n = 22), and supplemental
      parenteral glutamine (n = 17). The first RCTs were published in 1983 (n = 2), and
      the mean sample size was 39.0. In 2008, there were 26 RCTs, each enrolling an
      average of 237.1 patients. Excluding 2 cluster RCTs, 62 of 205 (30.2%) trials had
      concealed randomization, 125 of 205 (61.0%) reported on intention-to-treat
      analyses, and 69 of 205 (33.7%) had a double-blinded intervention; 18 of 205
      (8.8%) studies reported on all 3 design characteristics. Currently, 60 critical
      care nutrition RCTs (18 multicenter trials) are registered on clinical trials
      registries. CONCLUSIONS: The future of clinical critical care nutrition research
      is promising, with more trials of increasing sample size being conducted. Robust
      trial methodology, transparent reporting, and the development of research
      networks will help to further advance this important field.

PMID- 21097771
TI  - Creating a culture of clinical excellence in critical care nutrition: the 2008
      "Best of the Best" award.
AB  - OBJECTIVE: To develop, validate, and implement a system to reward top performers
      in critical care nutrition practice and to illuminate characteristics of top
      performing intensive care units (ICUs). DESIGN: An international, prospective,
      observational, cohort study conducted in May 2008. SETTING: 179 ICUs from 18
      countries. PATIENTS: 2956 consecutively enrolled mechanically ventilated adult
      patients who stayed in the ICU for at least 72 hours. INTERVENTIONS: To qualify
      for the "Best of the Best" (BOB) award, sites had to have implemented a nutrition
      protocol and contributed complete data on a minimum of 20 patients. MEASUREMENTS
      AND MAIN RESULTS: Data on nutrition practices were collected from ICU admission
      to ICU discharge for a maximum of 12 days. Eligible sites were ranked based on
      their performance on the following 5 criteria: adequacy of provision of energy,
      use of enteral nutrition (EN), early initiation of EN, use of promotility drugs
      and small bowel feeding tubes, and adequate glycemic control. Of the 179
      participating ICUs, 81 qualified for the BOB award. Overall, the average
      nutrition adequacy across sites was 56.2% (site range, 20.3%-90.1%). The top 10
      performers were identified and publicly recognized. Regression analysis suggested
      that the presence of a dietitian in the ICU was associated with a high BOB award
      ranking, whereas being located in the United States or China, relative to other
      participating countries, was associated with worst performance. CONCLUSIONS:
      There is variable performance with respect to critical care nutrition practices
      across the world.

PMID- 21097772
TI  - Quest for excellence: inspiration from the ileum.
AB  - The occasion of the American Society for Parenteral and Enteral Nutrition 33rd
      Presidential Address was used to glean wisdom and inspiration from the ileum. Not
      only is this intestinal segment so central to the chief organ involved in
      specialized nutrition support, but it is a complex, yet elegant system that: (1)
      is interdisciplinary with actions coordinated to achieve a common goal; (2) looks
      to the future by mentoring the next generation of leaders; (3) constantly seeks
      evidence of its effectiveness and accordingly adjusts its practice; and (4)
      strategically forges synergistic partnerships with other habitants within its
      environment. As relevant within many other realms, it remains true that much can
      be learned from looking within.

PMID- 21097773
TI  - Mosaic trisomy 13: understanding origin using SNP array.
AB  - BACKGROUND: Trisomy 13 occurs in 1/10,000-20,000 live births, and mosaicism
      accounts for 5% of these cases. Phenotype and outcome of mosaic trisomy 13 are
      variable and poorly understood. Microsatellite analyses of trisomy 13 have
      indicated the high incidence of maternal meiotic origin and reduced
      recombination, but no study has focused on mosaic trisomy 13 in live born
      patients. METHODS AND RESULTS: Single-nucleotide polymorphism (SNP) array,
      fluorescence in situ hybridisation and bioinformatics analyses were performed in
      three cases of mosaic trisomy 13. Two cases of complete mosaic trisomy 13
      originated from meiosis I non-disjunction followed by trisomic rescue; one had
      crossovers resulting in segmental uniparental disomy in the disomic line, and one
      had no crossover. Mosaicism for partial trisomy 13 in the third complex case
      either arose from meiosis II non-disjunction without crossover or in early
      mitosis followed by anaphase lags. The extra chromosome 13 was maternal in origin
      in all three cases. Mosaicism percentage calculated from B allele frequencies
      ranged from 30 to 50. CONCLUSIONS: Genotypes and copy number information provided
      by SNP array allow determination of parental origin and uniparental disomy status
      and direct quantification of mosaicism. Such information may lead to a better
      understanding of mechanisms underlying mosaic aneuploidies and the observed
      phenotypic variability and better prediction of recurrent risk.

PMID- 21097774
TI  - Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as
      modifiers for disease expression in Lynch syndrome.
AB  - OBJECTIVE: Recently, six colorectal cancer (CRC) susceptibility loci have been
      identified, and two single-nucleotide polymorphisms (SNPs)--rs16892766 (8q23.3)
      and rs3802842 (11q23.1)--from two of these regions have been found to be
      significantly associated with an increased CRC risk in patients with Lynch
      syndrome. The objective of this study was to genotype nine SNPs within these six
      loci to confirm previous findings and investigate whether they act as modifiers
      of disease risk in patients with Lynch syndrome. DESIGN: The patient cohort
      consisted of 684 mutation-positive patients with Lynch syndrome from 298
      Australian and Polish families. Nine SNPs were genotyped: rs16892766 (8q23.3),
      rs7014346 and rs6983267 (8q24.21), rs10795668 (10p14), rs3802842 (11q23.1),
      rs10318 and rs4779584 (15q13.3), and rs4939827 and rs4464148 (18q21.1). The data
      were analysed to investigate possible associations between the presence of
      variant alleles and the risk of developing disease. RESULTS: An association
      between SNP rs3802842 on chromosome 11q23.1 and rs16892766 on chromosome 8q23.3
      and the risk of developing CRC and age of diagnosis was found in MLH1 mutation
      carriers. Female MLH1 mutation carriers harbouring the homozygous variant
      genotype for SNP rs3802842 have the highest risk of developing CRC. When the
      number of risk alleles for the two SNPs combined was analysed, a difference of 24
      years was detected between individuals carrying three risk alleles and those
      carrying no risk alleles. CONCLUSION: The authors were able to replicate the
      association between the CRC susceptibility loci on chromosomes 8q23.3 and 11q23
      and the risk of developing CRC in patients with Lynch syndrome, but the
      association could only be detected in MLH1 mutation carriers in this study.

PMID- 21097775
TI  - Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an
      unusual cancer-predisposing mechanism.
AB  - Molecular studies in a patient with Beckwith-Wiedemann syndrome phenotype who
      developed two different tumours revealed an unexpected observation of almost
      complete loss of heterozygosity of all chromosomes. It is shown, by means of
      numerous molecular methods, that the absence of maternal contribution in somatic
      cells is due to high-degree (~ 85%) genome-wide paternal uniparental disomy
      (UPD). The observations indicate that the genome-wide UPD results from
      diploidisation, and have important implications for genetic counselling and
      tumour surveillance for the growing number of UPD associated imprinting
      disorders.

PMID- 21097776
TI  - Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up
      characterises the role of DNA repair.
AB  - BACKGROUND: The frequency of cancer, neurologic degeneration and mortality in
      xeroderma pigmentosum (XP) patients with defective DNA repair was determined in a
      four decade natural history study. METHODS: All 106 XP patients admitted to the
      National Institutes of Health from 1971 to 2009 were evaluated from clinical
      records and follow-up. RESULTS: In the 65 per cent (n=69) of patients with skin
      cancer, non-melanoma skin cancer (NMSC) was increased 10,000-fold and melanoma
      was increased 2000-fold in patients under age 20. The 9 year median age at
      diagnosis of first non-melanoma skin cancer (NMSC) (n=64) was significantly
      younger than the 22 year median age at diagnosis of first melanoma (n=38)-a
      relative age reversal from the general population suggesting different mechanisms
      of carcinogenesis between NMSC and melanoma. XP patients with pronounced burning
      on minimal sun exposure (n=65) were less likely to develop skin cancer than those
      who did not. This may be related to the extreme sun protection they receive from
      an earlier age, decreasing their total ultraviolet exposure. Progressive
      neurologic degeneration was present in 24% (n=25) with 16/25 in complementation
      group XP-D. The most common causes of death were skin cancer (34%, n=10),
      neurologic degeneration (31%, n=9), and internal cancer (17%, n=5). The median
      age at death (29 years) in XP patients with neurodegeneration was significantly
      younger than those XP patients without neurodegeneration (37 years) (p=0.02).
      CONCLUSION: This 39 year follow-up study of XP patients indicates a major role of
      DNA repair genes in the aetiology of skin cancer and neurologic degeneration.

PMID- 21097777
TI  - Tertiary contacts control switching of the SAM-I riboswitch.
AB  - Riboswitches are non-coding RNAs that control gene expression by sensing small
      molecules through changes in secondary structure. While secondary structure and
      ligand interactions are thought to control switching, the exact mechanism of
      control is unknown. Using a novel two-piece assay that competes the anti
      terminator against the aptamer, we directly monitor the process of switching. We
      find that the stabilization of key tertiary contacts controls both aptamer domain
      collapse and the switching of the SAM-I riboswitch from the aptamer to the
      expression platform conformation. Our experiments demonstrate that SAM binding
      induces structural alterations that indirectly stabilize the aptamer domain,
      preventing switching toward the expression platform conformer. These results,
      combined with a variety of structural probing experiments performed in this
      study, show that the collapse and stabilization of the aptamer domain are
      cooperative, relying on the sum of key tertiary contacts and the bimodal
      stability of the kink-turn motif for function. Here, ligand binding serves to
      shift the equilibrium of aptamer domain structures from a more open toward a more
      stable collapsed form by stabilizing tertiary interactions. Our data show that
      the thermodynamic landscape for riboswitch operation is finely balanced to allow
      large conformational rearrangements to be controlled by small molecule
      interactions.

PMID- 21097778
TI  - SPIKE: a database of highly curated human signaling pathways.
AB  - The rapid accumulation of knowledge on biological signaling pathways and their
      regulatory mechanisms has highlighted the need for specific repositories that can
      store, organize and allow retrieval of pathway information in a way that will be
      useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge
      Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal,
      containing highly curated interactions for particular human pathways, along with
      literature-referenced information on the nature of each interaction. To make
      database population and pathway comprehension straightforward, a simple yet
      informative data model is used, and pathways are laid out as maps that reflect
      the curator&rsquo;s understanding and make the utilization of the pathways easy.
      The database currently focuses primarily on pathways describing DNA damage
      response, cell cycle, programmed cell death and hearing related pathways.
      Pathways are regularly updated, and additional pathways are gradually added. The
      complete database and the individual maps are freely exportable in several
      formats. The database is accompanied by a stand-alone software tool for analysis
      and dynamic visualization of pathways.

PMID- 21097779
TI  - Extending CATH: increasing coverage of the protein structure universe and linking
      structure with function.
AB  - CATH version 3.3 (class, architecture, topology, homology) contains 128,688
      domains, 2386 homologous superfamilies and 1233 fold groups, and reflects a major
      focus on classifying structural genomics (SG) structures and transmembrane
      proteins, both of which are likely to add structural novelty to the database and
      therefore increase the coverage of protein fold space within CATH. For CATH
      version 3.4 we have significantly improved the presentation of sequence
      information and associated functional information for CATH superfamilies. The
      CATH superfamily pages now reflect both the functional and structural diversity
      within the superfamily and include structural alignments of close and distant
      relatives within the superfamily, annotated with functional information and
      details of conserved residues. A significantly more efficient search function for
      CATH has been established by implementing the search server Solr
      (http://lucene.apache.org/solr/). The CATH v3.4 webpages have been built using
      the Catalyst web framework.

PMID- 21097780
TI  - ModBase, a database of annotated comparative protein structure models, and
      associated resources.
AB  - ModBase (http://salilab.org/modbase) is a database of annotated comparative
      protein structure models. The models are calculated by ModPipe, an automated
      modeling pipeline that relies primarily on Modeller for fold assignment, sequence
      structure alignment, model building and model assessment
      (http://salilab.org/modeller/). ModBase currently contains 10,355,444 reliable
      models for domains in 2,421,920 unique protein sequences. ModBase allows users to
      update comparative models on demand, and request modeling of additional sequences
      through an interface to the ModWeb modeling server (http://salilab.org/modweb).
      ModBase models are available through the ModBase interface as well as the Protein
      Model Portal (http://www.proteinmodelportal.org/). Recently developed associated
      resources include the SALIGN server for multiple sequence and structure alignment
      (http://salilab.org/salign), the ModEval server for predicting the accuracy of
      protein structure models (http://salilab.org/modeval), the PCSS server for
      predicting which peptides bind to a given protein (http://salilab.org/pcss) and
      the FoXS server for calculating and fitting Small Angle X-ray Scattering profiles
      (http://salilab.org/foxs).

PMID- 21097781
TI  - FlyFactorSurvey: a database of Drosophila transcription factor binding
      specificities determined using the bacterial one-hybrid system.
AB  - FlyFactorSurvey (http://pgfe.umassmed.edu/TFDBS/) is a database of DNA binding
      specificities for Drosophila transcription factors (TFs) primarily determined
      using the bacterial one-hybrid system. The database provides community access to
      over 400 recognition motifs and position weight matrices for over 200 TFs,
      including many unpublished motifs. Search tools and flat file downloads are
      provided to retrieve binding site information (as sequences, matrices and
      sequence logos) for individual TFs, groups of TFs or for all TFs with
      characterized binding specificities. Linked analysis tools allow users to
      identify motifs within our database that share similarity to a query matrix or to
      view the distribution of occurrences of an individual motif throughout the
      Drosophila genome. Together, this database and its associated tools provide
      computational and experimental biologists with resources to predict interactions
      between Drosophila TFs and target cis-regulatory sequences.

PMID- 21097782
TI  - DIMA 3.0: Domain Interaction Map.
AB  - Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is
      a database of predicted and known interactions between protein domains. It
      integrates 5807 structurally known interactions imported from the iPfam and 3did
      databases and 46,900 domain interactions predicted by four computational methods:
      domain phylogenetic profiling, domain pair exclusion algorithm correlated
      mutations and domain interaction prediction in a discriminative way. Additionally
      predictions are filtered to exclude those domain pairs that are reported as non
      interacting by the Negatome database. The DIMA Web site allows to calculate
      domain interaction networks either for a domain of interest or for entire
      organisms, and to explore them interactively using the Flash-based Cytoscape Web
      software.

PMID- 21097784
TI  - Can interventions improve health services from informal private providers in low
      and middle-income countries?: a comprehensive review of the literature.
AB  - BACKGROUND There is a growing interest in the role of private health providers in
      low- and middle-income countries (LMICs). Informal private providers (IPPs)
      provide a significant portion of health care in many LMICs, but they have not
      received training in allopathic medicine. Interventions have been developed to
      take advantage of their potential to expand access to essential health services,
      although their success is not well measured. This paper addresses this
      information gap through a review of interventions designed to improve the
      quality, coverage, or costs of health services provided by IPPs in LMICs. METHODS
      A search for published literature in the last 15 years for any intervention
      dealing with IPPs in a LMIC, where at least one outcome was measured, was
      conducted through electronic databases PubMed and Global Health, as well as
      Google for grey literature from the Internet. RESULTS A total of 1272 articles
      were retrieved, of which 70 separate studies met inclusion criteria. The majority
      (70%) of outcomes measured proximate indicators such as provider knowledge (61%
      were positive) and behaviour (56% positive). Training IPPs was the most common
      intervention tested (77% of studies), but the more effective strategies did not
      involve training alone. Interventions that changed the institutional
      relationships and contributed to changing the incentives and accountability
      environment were most successful, and often required combinations of
      interventions. CONCLUSION Although there are documented interventions among IPPs,
      there are few good quality studies. Strategies that change the market conditions
      for IPPs-by changing incentives and accountability-appear more likely to succeed
      than those that depend on building individual capacities of IPPs. Understanding
      the effectiveness of these and other strategies will also require more rigorous
      research designs that assess contextual factors and document outcomes over longer
      periods.

PMID- 21097783
TI  - KaPPA-View4: a metabolic pathway database for representation and analysis of
      correlation networks of gene co-expression and metabolite co-accumulation and
      omics data.
AB  - Correlations of gene-to-gene co-expression and metabolite-to-metabolite co
      accumulation calculated from large amounts of transcriptome and metabolome data
      are useful for uncovering unknown functions of genes, functional diversities of
      gene family members and regulatory mechanisms of metabolic pathway flows. Many
      databases and tools are available to interpret quantitative transcriptome and
      metabolome data, but there are only limited ones that connect correlation data to
      biological knowledge and can be utilized to find biological significance of it.
      We report here a new metabolic pathway database, KaPPA-View4
      (http://kpv.kazusa.or.jp/kpv4/), which is able to overlay gene-to-gene and/or
      metabolite-to-metabolite relationships as curves on a metabolic pathway map, or
      on a combination of up to four maps. This representation would help to discover,
      for example, novel functions of a transcription factor that regulates genes on a
      metabolic pathway. Pathway maps of the Kyoto Encyclopedia of Genes and Genomes
      (KEGG) and maps generated from their gene classifications are available at KaPPA
      View4 KEGG version (http://kpv.kazusa.or.jp/kpv4-kegg/). At present, gene co
      expression data from the databases ATTED-II, COXPRESdb, CoP and MiBASE for human,
      mouse, rat, Arabidopsis, rice, tomato and other plants are available.

PMID- 21097785
TI  - The comparison of solitary topical micafungin or fluconazole application in the
      treatment of Candida fungal keratitis.
AB  - AIM: To compare and evaluate the efficacy of topical 0.1% micafungin (MCFG) and
      topical 0.2% fluconazole (FCZ) in the treatment of Candida fungal keratitis.
      METHODS: Twenty-nine eyes of 29 patients who were diagnosed as having Candida
      fungal keratitis, proven by corneal culture isolates, were investigated in this
      prospective study. Patients were divided into a MCFG treatment group (12 eyes)
      and an FCZ treatment group (17 eyes). Age, gender, initial status of ulcer (ulcer
      size and degree of injection), initial and final best-corrected visual acuity
      (BCVA), healing periods, final status of cornea and recurrences in each group
      were studied and compared. RESULTS: There were no significant differences in
      relation to age, gender, ulcer size and degree of injection before treatment
      between the two groups. There were also no significant differences in the healing
      periods until complete epithelialisation (MCFG treatment group (41.3 +/- 38.0
      days); FCZ treatment group (34.4 +/- 37.7 days)), change in BCVA, corneal
      clarity/opacification, perforation and recurrence status at the final examination
      between the two groups. CONCLUSION: The efficacy of 0.1% MCFG eye-drops appears
      to be comparable with that of 0.2% FCZ eye-drops in the treatment of Candida
      fungal keratitis.

PMID- 21097786
TI  - Long-term results of autologous cultivated oral mucosal epithelial
      transplantation in the scar phase of severe ocular surface disorders.
AB  - PURPOSE: To investigate the long-term outcome of autologous cultivated oral
      mucosal epithelial transplantation (COMET) for the treatment of the scar phase of
      severe ocular surface disorders. Participants This study involved 19 eyes of 17
      patients who received autologous COMET for total limbal stem-cell deficiency.
      METHODS: Autologous cultivated oral mucosal epithelial sheets were created using
      amniotic membrane as a substrate. Clinical efficacy was evaluated by best
      corrected visual acuity and visual acuity at the postoperative 36th month. The
      clinical results (clinical conjunctivalisation, corneal opacification, corneal
      neovascularisation and symblepharon formation) were evaluated and graded on a
      scale from 0 to 3 according to their severity. Clinical safety was evaluated by
      the presence of persistent epithelial defects, ocular hypertension and
      infections. RESULTS: Autologous cultivated oral mucosal epithelial sheets were
      successfully generated for all 17 patients. All patients were followed up for
      more than 36 months; the mean follow-up period was 55 months and the longest
      follow-up period was 90 months. During the long-term follow-up period,
      postoperative conjunctivalisation and symblepharon were significantly inhibited.
      All eyes manifested various degrees of postoperative corneal neovascularisation,
      but it gradually abated and its activity was stable at 6 months after surgery.
      Best-corrected visual acuity was improved in 18 eyes (95%) during the follow-up
      periods, and visual acuity at the postoperative 36th month was improved in 10
      eyes (53%). CONCLUSIONS: These long-term clinical results strongly support the
      conclusion that tissue-engineered cultivated oral mucosal epithelial sheets are
      useful in reconstructing the ocular surface of the scar phase of severe ocular
      surface disorders.

PMID- 21097787
TI  - Reproducibility of high-resolution optical coherence tomography measurements of
      the nerve fibre layer with the new Heidelberg Spectralis optical coherence
      tomography.
AB  - AIM: Conventional time-domain OCT technology for detection of retinal nerve fibre
      layer (RNFL) neurodegeneration suffers from technical inaccuracy owing to a lack
      of exact scan centring around the optic disc as well as a true follow-up
      possibility. In this study, the authors evaluated a novel high-resolution
      spectral-domain OCT device (SD-OCT) with an incorporated eye-tracking feature in
      its ability to objectively measure the RNFL thickness (RNFLT) by testing
      intraobserver reproducibility in a series of healthy volunteers. METHODS:
      Triplicate circumferential RNFL scans of six peripapillary sectors were obtained
      from both eyes of all 31 participants. The authors compared the measurements of
      RNFLT during three separate examination days under miotic (Mi) and mydriatic (My)
      pupil conditions using a high-speed (HS) and high-resolution (HR) scan
      acquisition mode. To examine the intersession reproducibility of the SD-OCT
      measurements, the mean, SD and coefficient of variation (COV) were calculated.
      RESULTS: No significant differences were found in all groups, independent of the
      mode of image acquisition and examination day (p always >0,05). Under all
      conditions, low COVs between 0.545% and 3.97% (intrasession COV on baseline) were
      found. The intersession COV with activated follow-up mode ranged between 0.29%
      and 1.07%. In both settings, the temporal sector showed the highest COV values.
      CONCLUSIONS: True follow-up measurement of identical peripapillary regions may
      enable clinicians to detect discrete levels of retinal thickness change over
      time. This constitutes a crucial prerequisite for a reliable monitoring of subtle
      RNFL changes in neurodegenerative disorders.

PMID- 21097788
TI  - Treating patients presenting with advanced glaucoma--should we reconsider current
      practice?
AB  - The management of patients presenting with advanced glaucoma presents a challenge
      to glaucoma clinicians. Presentation with advanced visual field loss is an
      important risk factor for progression to blindness in the affected eye(s) during
      the patients' lifetime. Maximising intraocular pressure (IOP) control in such
      situations is likely to minimise the risk of further visual field deterioration
      thus either preventing or slowing progression to blindness. Currently most
      patients presenting with advanced disease in the UK are managed on an escalating
      regime of medical treatment. Should this fail glaucoma surgery is usually
      employed to further lower IOP. Although glaucoma surgery is generally a safe and
      successful intervention it carries a small risk of severe visual loss and is
      considered by many clinicians as an intervention only to be used following
      failure of medical treatment. Recently however the National Institute for
      Clinical Excellence has suggested in its clinical guidelines for management of
      ocular hypertension and glaucoma that primary surgery should be offered to
      patients presenting with advanced glaucomatous visual field loss. This is
      contrary to the practice of most UK ophthalmologists. In this review the current
      available evidence underlying the management of presentation with advanced
      disease is examined.

PMID- 21097789
TI  - Analysis of the IgVH genes in T cell-mediated and antibody-mediated rejection of
      the kidney graft.
AB  - AIMS: Grafts have been shown to be sites where the alloimmune response develops
      in a direct interaction between the targeted tissue and the immune effectors. An
      important issue in renal rejection is B cell infiltrate that may contribute to
      the development or persistence of rejection. Analysis of gene-expression patterns
      also provides a window on the biology and pathogenesis of renal allograft
      rejection. METHODS: To better understand the role exerted by B cells in a renal
      acute rejection, the authors analysed the IgVH gene repertoire in six cases of
      transplanted kidneys with acute T cell-mediated rejection (TCMR), three of which
      were associated with antibody-mediated rejection (ABMR). RESULTS: The authors
      found mutated and unmutated sequences, without any evidence of clonal
      relationships, in all patients with TCMR alone and in two of the three cases with
      both acute TCMR and ABMR. The remaining patient showed glomerular inflammation
      and thrombosis, with diffuse C4d glomerular and peritubular capillary deposition,
      and hypermutated V region genes. CONCLUSIONS: These results suggest that there is
      more than one pathway to the onset and perpetuation of CD20 (+) B cells
      infiltration in acute rejection; furthermore, the CD20 (+) B cells' clonal
      expansion may be responsible for a more severe pattern of ABMR, through immune
      mediated tissue damage.

PMID- 21097790
TI  - Composite papillary intestinal-type adenocarcinoma/poorly differentiated
      neuroendocrine carcinoma of the ampulla of Vater.

PMID- 21097791
TI  - Conservative management of screen-detected radial scars: role of mammotome
      excision.
AB  - AIMS: Traditionally, a core biopsy diagnosis of radial scar will prompt
      diagnostic surgery because of the risk of associated malignancy. However, in the
      absence of atypia, the risk of malignancy is low. The recent introduction of the
      mammotome device facilitates vacuum-assisted large-volume sampling of a lesion,
      such that a benign diagnosis may be accepted more confidently, and if the lesion
      has been entirely removed, it effectively becomes a therapeutic procedure. The
      aim of this study was to review the role of mammotome excision in the management
      of non-atypical radial scars in the screening population. METHODS: Screen
      detected radial scars diagnosed on core biopsy between July 2004 and September
      2008 were identified from pathology records. From January 2006, the mammotome
      device was used to excise non-atypical radial scars on core biopsy, as an
      alternative to surgery. RESULTS: 22 core biopsy samples containing radial scars
      without atypia were included in the study; 14 were planned for mammotome excision
      and eight for diagnostic surgical excision. In the mammotome group, 78% (11/14)
      of patients had confirmation of non-atypical radial scars and thus avoided an
      operation. Three of the 14 cases planned for mammotome excision required surgery;
      in one case, the mammotome cores contained lobular in situ neoplasia, and, in two
      cases, attempts to sample the lesion with the mammotome were unsuccessful. Only
      one of the 22 cases ultimately proved malignant. This was a case of ductal
      carcinoma in situ arising within a radial scar, where the patient proceeded
      straight to surgery in view of discordance between radiological and pathological
      features. CONCLUSION: Utilisation of mammotome excision in the management of non
      atypical radial scars successfully avoided surgery in 78% of eligible patients.
      Pathologists have an important role in selecting patients for mammotome excision
      by excluding the presence of atypia.

PMID- 21097792
TI  - Injection anthrax causing compartment syndrome and necrotising fasciitis.

PMID- 21097793
TI  - Abnormal liver function in children with metabolic syndrome from a UK-based
      obesity clinic.
AB  - AIM: To examine transaminitis in obese children, its association with glucose
      metabolism and the metabolic syndrome and the response to weight loss through
      lifestyle modification. METHODS: 216 children (90 male), aged 2.9-17.6 (median
      12.4 years) with median body mass index (BMI) SD score (SDS) of 3.36 (range 1.92
      6.22) attending a hospital obesity clinic in Bristol (UK) underwent an oral
      glucose tolerance test (OGTT) with fasting lipid and liver profile. Auxological
      measures included weight, height, waist circumference, percentage body fat.
      Parental history of type 2 diabetes (T2DM) was recorded. The 2007 International
      Diabetes Federation definition of metabolic syndrome was used. 90 children
      undergoing a trial of lifestyle modification to improve weight were re-assessed
      at 12 months. RESULTS: 34/216 (16%) children had raised alanine aminotransferase
      (ALT) (>40 IU/l) with greater prevalence in boys (23% vs 10%, p=0.01) and in
      those with a parental history of T2DM (30% vs 13.2% p=0.019). Patients with
      transaminitis were more likely to fulfil the criteria for metabolic syndrome
      (p<0.001) and have subtle abnormalities in glucose metabolism during an OGTT with
      elevated glucose levels at 90 (p=0.041) and 120 (p=0.014) min and a greater
      glucose area-under-the-curve (p=0.014). Improvement in BMI SDS over 1 year
      correlated with improvement in ALT levels (tau = -0.29, p<0.001). CONCLUSION:
      Prevalence of transaminitis is significant in obese children and is associated
      with components of the metabolic syndrome. Lifestyle-based improvement in BMI SDS
      offers an effective tool for correcting transaminitis and should remain the
      central component of therapy.

PMID- 21097794
TI  - 'This House believes that we have gone too far in granting young people the
      responsibility for making decisions about their own healthcare': record of a
      debate held in the Ethics and Law session of the RCPCH Annual Meeting, York 2009.

PMID- 21097795
TI  - True adherence with the Turbuhaler in young children with asthma.
AB  - OBJECTIVE: To investigate true adherence with a dry powder inhaler, the
      Turbuhaler (TBH), in children with asthma. True adherence was calculated by
      multiplying adherence to treatment with inhaler competence, that is correct use
      of the inhaler. PATIENTS AND DESIGN: In an 18-month study, children aged 5-10
      years with asthma received twice daily budesonide via a TBH. Parents and children
      were trained in the correct use of the inhaler before the study started. For each
      inhalation, peak inspiratory flow through the TBH (PIF(TBH)) was recorded with an
      electronic pneumotachograph. The PIF(TBH) recordings were used to calculate true
      adherence for the first and last 45-day periods in the study by multiplying
      adherence in using the device (percentage of days with PIF(TBH) recordings) with
      inhaler competence (correct use of inhaler defined as PIF(TBH) values >40 l/min).
      MAIN OUTCOME MEASURES: True adherence, adherence, inhaler competence and
      PIF(TBH). RESULTS: 115 children were treated. The mean (morning and evening) true
      adherence during the first 45 days was 81.6% (range 78.1-86.4%) and during the
      last 45 days 57.4% (44.0-66.9%). Mean adherence was 86.0% and 59.3%, whereas mean
      inhaler competence was 94.7% and 96.2%, respectively. Thus the decline in true
      adherence was due to the decline in adherence. The largest decline in true
      adherence occurred in older children. CONCLUSIONS: True adherence with budesonide
      TBH treatment decreased significantly during the 18-month study due to a decrease
      in adherence. Inhaler competence with the correct use of the budesonide TBH was
      high and unchanged over the study period.

PMID- 21097799
TI  - Clinical and ultrasonographic remission determines different chances of relapse
      in early and long standing rheumatoid arthritis.
AB  - OBJECTIVES: Treatment of rheumatoid arthritis (RA) should aim at full remission.
      The aims of this study were to define: (1) how many patients reached ultrasound
      power Doppler (US-PD) remission in a cohort of patients with early RA (ERA)
      compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission;
      and (3) how many patients with and without US-PD remission relapsed after 1 year
      of follow-up in ERA and LSRA. METHODS: 48 patients with ERA and 46 with LSRA with
      disease activity score <1.6 underwent US assessment. Six hand and wrist joints
      were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those
      with LSRA fulfilled American College of Rheumatology (ACR) remission criteria.
      RESULTS: 43.7% of patients with ERA and 17.4% of those with LSRA had no evidence
      of synovitis at US evaluation. Using a stricter clinical definition of remission
      (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of
      patients with ERA and 26.1% of those with LSRA. Early disease was predictive of
      clinical US remission. 20.0% of patients with RA who had a negative PD signal at
      the US evaluation had a flare during the 12-month follow-up period compared with
      47.1% of patients who had a positive PD signal. CONCLUSION: US-PD remission
      occurs in half of patients with ERA and in a minority of patients with LSRA in
      clinical remission. Early disease seems to be the major determinant of full
      remission.

PMID- 21097800
TI  - Reduction of regulatory T cells in skin lesions but not in peripheral blood of
      patients with systemic scleroderma.
AB  - OBJECTIVE: To determine the frequency and suppressive capacity of regulatory T
      cells (T(reg)) and their association with clinical parameters in patients with
      systemic scleroderma (SSc). METHODS: Peripheral blood from 25 patients with SSc,
      15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was
      studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+)
      T(reg) subpopulations was carried out by flow cytometry and cell proliferation
      was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg)
      was further performed in skin biopsies from 17 patients with SSc and 21 patients
      with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for
      immunohistochemistry. RESULTS: The frequency of CD4(+)Foxp3(+) and
      CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not
      significantly different from that of patients with LS or HC. The suppressive
      capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of
      HC. Phenotypic and functional data revealed no significant difference between the
      limited or diffuse form of SSc. Moreover, therapy with bosentan showed no
      significant effect on the frequency of T(reg) during the course of the disease.
      However, the frequency of T(reg) in skin lesions from patients with SSc or LS,
      determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory
      infiltrate, was significantly reduced compared with other inflammatory skin
      diseases. CONCLUSION: These results indicate that although the authors found no
      defect in the frequency or function of peripheral T(reg) subpopulations, the
      reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be
      important in the pathogenesis of the disease.

PMID- 21097801
TI  - Indirect comparisons of the efficacy of biological antirheumatic agents in
      rheumatoid arthritis in patients with an inadequate response to conventional
      disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent:
      a meta-analysis.
AB  - BACKGROUND: The availability of increasing numbers of biological agents for the
      treatment of rheumatoid arthritis (RA) offers several therapeutic options. While
      all biologicals have proven effective in trials, very limited direct comparisons
      are available. The objective of the present work was to compare the efficacy of
      biologicals (anti-tumour necrosis factor (TNF) agents, rituximab, abatacept,
      tocilizumab) in patients with RA with active disease and (i) an inadequate
      response (IR) to methotrexate (IR-MTX), (ii) an IR to anti-TNF agents (IR-anti
      TNFs) using indirect comparisons. METHODS: Randomised clinical trials were
      identified examining the efficacy of a biological agent in RA at 6 months in
      patients with an IR-MTX or with an IR-anti-TNF. To compare the relative efficacy
      of biologicals, adjusted indirect comparison meta-analytic methods to estimate
      the ORs of achieving a 50% improvement according to American College of
      Rheumatology criteria (ACR50) response at 6 months were used. RESULTS: A total of
      18 published trials and 1 abstract were included in the analyses. In IR-MTX, anti
      TNFs had the same probability of reaching an ACR50 compared to 'non-anti-TNF
      biologicals' taken together (OR 1.30, 95 % CI 0.91 to 1.86). However, when
      compared to specific biological agents, anti-TNFs demonstrated a higher
      probability of reaching an ACR50 than abatacept (OR 1.52, 95 % CI 1.0 to 2.28),
      but not in comparison to rituximab and tocilizumab. In IR-anti-TNF, no
      significant differences existed between rituximab, tocilizumab, abatacept and
      golimumab. [corrected] CONCLUSIONS: In a meta-analysis of randomised clinical
      trials of patients with IR-MTX, anti-TNFs demonstrated a higher probability of
      achieving an ACR50 response than abatacept. In IR-anti-TNF, no difference was
      found between rituximab, tocimizumab, abatacept and golimumab.

PMID- 21097802
TI  - Systemic and local factors are involved in the evolution of erosions in hand
      osteoarthritis.
AB  - OBJECTIVE: In order to gain insight in the pathogenesis of erosive hand
      osteoarthritis (OA), the evolution of erosions in hand OA and risk factors
      involved were investigated. METHODS: The 6-year evolution in radiographic
      Verbruggen-Veys anatomical phase was assessed in interphalangeal joints of 236
      patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics
      ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase
      transitions from non-erosive to erosive phases and from active erosions to
      remodelling. Clustering of erosive evolution within patients was assessed using
      the chi2 test. Familial aggregation was evaluated in sibling pairs by estimating
      ORs for siblings and probands sharing erosive evolution. Local baseline
      determinants and the effect of high sensitivity C reactive protein were assessed
      using generalised estimating equations. RESULTS: Erosive evolution took place in
      181 of 4120 interphalangeal joints at risk (4.4%), corresponding to 60 patients
      (25.4% of study sample). Erosive evolution was found more often in multiple
      interphalangeal joints in one patient than would be expected by chance (chi2
      373.0, p < 0.001). The adjusted OR (95% CI) for a sibling having erosive
      evolution if the proband had erosive evolution was 4.7 (1.4 to 15.8). Systemic
      inflammation was not associated with erosive activity. Independent local
      determinants were joint space narrowing (OR (95% CI) 8.9 (4.8 to 16.4)) and self
      reported pain (OR (95%CI) 2.3 (1.1 to 4.7)). CONCLUSIONS: rosive evolution was
      clustered within patients and families. Local factors were also involved in the
      evolution. This increase in insight in the pathogenesis of erosive hand OA will
      contribute to the development of new treatments.

PMID- 21097803
TI  - Definition of remission and relapse in polymyalgia rheumatica: data from a
      literature search compared with a Delphi-based expert consensus.
AB  - OBJECTIVE: To compare current definitions of remission and relapse in polymyalgia
      rheumatica (PMR) with items resulting from a Delphi-based expert consensus.
      METHODS: Relevant studies including definitions of PMR remission and relapse were
      identified by literature search in PubMed. The questionnaire used for the Delphi
      survey included clinical (n=33), laboratory (n=54) and imaging (n=7) parameters
      retrieved from a literature search. Each item was assessed for importance and
      availability/practicability, and limits were considered for metric parameters.
      Consensus was defined by an agreement rate of >=80%. RESULTS: Out of 6031
      articles screened, definitions of PMR remission and relapse were available in 18
      and 34 studies, respectively. Parameters used to define remission and/or relapse
      included history and clinical assessment of pain and synovitis, constitutional
      symptoms, morning stiffness (MS), physician's global assessment, headache,
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count,
      fibrinogen and/or corticosteroid therapy. In the Delphi exercise a consensus was
      obtained on the following parameters deemed essential for definitions of
      remission and relapse: patient's pain assessment, MS, ESR, CRP, shoulder and hip
      pain on clinical examination, limitation of upper limb elevation, and assessment
      of corticosteroid dose required to control symptoms. CONCLUSIONS: Assessment of
      patient's pain, MS, ESR, CRP, shoulder pain/limitation on clinical examination
      and corticosteroid dose are considered to be important in current available
      definitions of PMR remission and relapse and the present expert consensus. The
      high relevance of clinical assessment of hips was unique to this study and may
      improve specificity and sensitivity of definitions for remission and relapse in
      PMR.

PMID- 21097804
TI  - Long-term effects of intrauterine growth restriction on cardiac metabolism and
      susceptibility to ischaemia/reperfusion.
AB  - AIMS: Adult offspring who are born intrauterine growth restricted (IUGR) are at
      risk of developing cardiovascular diseases during adulthood. Additionally,
      several cardiac diseases are associated with changes in myocardial energy
      metabolism. However, the potential long-term effects of being born IUGR on
      cardiac energetics are unknown. The aim of this study was to assess the long-term
      effect of IUGR on cardiac performance and energy metabolism under aerobic
      conditions and after ischaemia/reperfusion (IR) injury. METHODS AND RESULTS: To
      induce IUGR, pregnant Sprague-Dawley rats were randomly assigned to hypoxic
      (11.5% O(2)) or control (21% O(2)) environments from day 15 to 21 of pregnancy.
      Cardiac susceptibility to IR was evaluated in male and female offspring at 4
      (young-adult) or 12 (ageing) months of age using isolated working hearts. Cardiac
      production of energy was evaluated using radiolabelled substrates. Both male and
      female IUGR offspring exhibited an increased susceptibility to IR injury compared
      with controls (P< 0.05) as well as an increased post-ischaemic production of
      protons (P< 0.001) secondary to a mismatch between myocardial glycolysis and
      glucose oxidation rates. Moreover, offspring born IUGR exhibited an increased
      myocardial production of acetyl-CoA during reperfusion. The mismatch between
      energy production and cardiac performance indicates that in IUGR offspring,
      cardiac efficiency during reperfusion was decreased relative to controls.
      CONCLUSION: Our results suggest that hypoxia-induced IUGR has long-term effects
      on cardiac susceptibility to IR injury that are independent of sex and age.
      Moreover, we identified a mismatch in glucose metabolism, leading to proton
      accumulation in the post-ischaemic myocardium of offspring born IUGR as a
      potential mechanism involved.

PMID- 21097805
TI  - The Na(+), K(+)-ATPase: more than just a sodium pump.

PMID- 21097806
TI  - Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries,
      and reduces blood pressure in salt-induced hypertension.
AB  - AIMS: Reduced bioavailability of endogenous nitric oxide (NO) is a central
      pathophysiological event in hypertension and other cardiovascular diseases.
      Recently, it was demonstrated that inorganic nitrate from dietary sources is
      converted in vivo to form nitrite, NO, and other bioactive nitrogen oxides. We
      tested the hypothesis that dietary inorganic nitrate supplementation may have
      therapeutic effects in a model of renal and cardiovascular disease. METHODS AND
      RESULTS: Sprague-Dawley rats subjected to unilateral nephrectomy and chronic high
      salt diet from 3 weeks of age developed hypertension, cardiac hypertrophy and
      fibrosis, proteinuria, and histological as well as biochemical signs of renal
      damage and oxidative stress. Simultaneous nitrate treatment (0.1 or 1 mmol
      nitrate kg-1 day-1), with the lower dose resembling the nitrate content of a diet
      rich in vegetables, attenuated hypertension dose-dependently with no signs of
      tolerance. Nitrate treatment almost completely prevented proteinuria and
      histological signs of renal injury, and the cardiac hypertrophy and fibrosis were
      attenuated. Mechanistically, dietary nitrate restored the tissue levels of
      bioactive nitrogen oxides and reduced the levels of oxidative stress markers in
      plasma (malondialdehyde) and urine (Class VI F2-isoprostanes and 8-hydroxy-2
      deoxyguanosine). In addition, the increased circulating and urinary levels of
      dimethylarginines (ADMA and SDMA) in the hypertensive rats were normalized by
      nitrate supplementation. CONCLUSION: Dietary inorganic nitrate is strongly
      protective in this model of renal and cardiovascular disease. Future studies will
      reveal if nitrate contributes to the well-known cardioprotective effects of a
      diet rich in vegetables.

PMID- 21097808
TI  - Incorporating uncertainty in aggregate burden of disease measures: an example of
      DALYs-averted by a smoking cessation campaign in the UK.
AB  - BACKGROUND: Summary measures of population health (SMPH) combine information
      about morbidity and mortality as a means of describing the health of a population
      and allow for the comparison between otherwise incomparable health problems.
      Despite the widespread use of SMPHs in global public health policy, the
      uncertainty in their calculation, inherent due to the variable quality and
      availability of data from different sources required to calculate SMPHs, is
      generally ignored. METHODS AND RESULTS: Using the example of the expected effect
      of a smoking cessation mass-media campaign on ischaemic heart disease in the UK
      expressed in DALYs (disability adjusted life years)-averted, a transparent and
      straightforward probabilistic methodology to incorporate uncertainty in the
      calculation of population impact measures of health, to better inform the public
      health debate, is described. In addition, a rationale on how this additional
      information can be utilised to further improve the use of quantitative data for
      SMPH is presented, and public health policy makers are provided with additional
      tools for prioritisation of interventions and cost-effective prioritisation of
      data collection campaigns for the improvement of the calculation of future SMPH.
      CONCLUSION: Systematic use of these tools will provide a stronger evidence base
      for public health policy in the future and will further direct a drive towards
      the use of quantitative tools.

PMID- 21097807
TI  - Deja vu in the theories of atrial fibrillation dynamics.
AB  - This brief review looks back to the major theoretical, experimental, and clinical
      work on the dynamics and mechanisms of atrial fibrillation (AF). Its goal is to
      highlight the most important issues, controversies, and advances that have driven
      the field of investigation into AF mechanisms at any given time during the last
      ~100 years. It emphasizes that while the history of AF research has been full of
      controversies from the start, such controversies have led to new information, and
      individual scientists have learned from those that have preceded them. However,
      in the face of the most common sustained cardiac arrhythmia seen in clinical
      practice, we are yet to fully understand its fundamental mechanisms and learn how
      to treat it effectively. Future research into AF dynamics and mechanisms should
      focus on the development and validation of new numerical and animal models. Such
      models should be relevant to and accurately reproduce the important substrates
      associated with ageing and with diseases such as hypertension, heart failure, and
      ischaemic heart disease which cause AF in the vast majority of patients.
      Knowledge derived from such models may help to greatly advance the field and
      hopefully lead to more effective prevention and therapy.

PMID- 21097809
TI  - Older people are at risk of sexually transmitted infections.

PMID- 21097810
TI  - Projected cost-savings with herpes simplex virus screening in pregnancy: towards
      a new screening paradigm.
AB  - OBJECTIVES: Herpes simplex virus (HSV) infections in newborns are an uncommon but
      potentially devastating consequence of genital HSV infection in women. Current
      practice focuses on preventing perinatal transmission by women with prevalent
      HSV, but transmission risk is greatest when genital HSV is acquired for the first
      time late in pregnancy. The objective of this study was to assess the
      effectiveness and cost effectiveness of identifying pregnant women at risk of de
      novo HSV acquisition as a means of preventing vertical HSV transmission. METHODS:
      A Bayesian decision tree model was parameterized using the best available health
      and economic data relating to HSV in pregnancy and was used to evaluate the cost
      effectiveness of screening to identify individuals susceptible to HSV infection
      in a hypothetical cohort of 100,000 pregnant women in their second trimester of
      pregnancy. Final outcomes were the projected incidence of maternal and neonatal
      HSV, quality-adjusted life expectancy and life-time costs associated with
      neonatal HSV. RESULTS: In the absence of testing, model projected incidence of
      neonatal HSV was 34 cases per 100,000 births, similar to available surveillance
      data. Screening pregnant women and their partners was projected to decrease the
      incidence of HSV-1 and HSV-2 infections in women and infants and to save costs.
      These findings were robust under alternative assumptions and in wide-ranging
      sensitivity analyses. CONCLUSIONS: The use of accurate and relatively inexpensive
      serological tests for HSV to identify women vulnerable to incident HSV infection
      in pregnancy has the potential to reduce neonatal HSV incidence and reduce health
      related costs.

PMID- 21097811
TI  - Impact of intensified testing for urogenital Chlamydia trachomatis infections: a
      randomised study with 9-year follow-up.
AB  - BACKGROUND: DNA amplification assays are increasingly being used to facilitate
      the testing of asymptomatic individuals for urogenital Chlamydia trachomatis. The
      long-term clinical benefit in terms of avoided infertility and ectopic pregnancy
      is unknown. METHODS: In 1997, 15,459 women and 14,980 men aged 21-23 years were
      living in Aarhus County, Denmark. A random sample of 4000 women and 5000 men was
      contacted by mail and offered the opportunity to be tested for C trachomatis by
      means of a sample obtained at home and mailed directly to the laboratory. The
      remaining 11,459 women and 9980 men received usual care and constituted the
      control population. All men and women were subsequently followed for 9 years by
      the use of Danish health registers. Data were collected on pelvic inflammatory
      disease (PID), ectopic pregnancy (EP), infertility diagnoses, in-vitro
      fertilisation (IVF) treatment and births in women, and on epididymitis in men.
      The intervention and control groups were compared using Cox regression analyses
      and the intention-to-screen principle. RESULTS: Among women, no differences were
      found between the intervention group and the control group: HR (95% CI) for PID
      1.12 (0.70 to 1.79); EP 0.97 (0.63 to 1.51); infertility 0.87 (0.71 to 1.07); IVF
      treatment 0.88 (0.62 to 1.26) and births 1.02 (0.95 to 1.10). In men, the HR for
      epididymitis was 1.25 (0.70 to 2.24). CONCLUSIONS: A population-based offer to be
      tested for urogenital C trachomatis infection by the use of non-invasive samples
      and DNA amplification did not reduce the long-term risk of reproductive
      complications in women or of epididymitis in men.

PMID- 21097812
TI  - Bringing it all back home: can Europeans learn from recent moves toward the
      medical home in US primary health care reform?

PMID- 21097813
TI  - A vision revisited: two years later on health reform in the USA.

PMID- 21097815
TI  - The learning curve for EBUS-TBNA.

PMID- 21097816
TI  - Effects of exercise on mitochondrial DNA content in skeletal muscle of patients
      with COPD.
AB  - BACKGROUND: Exhausting exercise reduces the mitochondrial DNA (mtDNA) content in
      the skeletal muscle of healthy subjects due to oxidative damage. Since patients
      with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative
      stress during exercise, it was hypothesised that the mtDNA content will be
      further reduced. OBJECTIVE: To investigate the effects of exercise above and
      below the lactate threshold (LT) on the mtDNA content of skeletal muscle of
      patients with COPD. METHODS: Eleven patients with COPD (67 +/- 8 years; forced
      expiratory volume in 1 s (FEV1) 45 +/- 8%ref) and 10 healthy controls (66 +/- 4
      years; FEV1 90 +/- 7% ref) cycled 45 min above LT (65% peak oxygen uptake
      (V'o2peak) and another 7 patients (65 +/- 6 years; FEV1 50 +/- 4%ref) and 7
      controls (56 +/- 9 years; FEV1 92 +/- 6% ref) cycled 45 min below their LT (50%
      V'o2peak). Biopsies from the vastus lateralis muscle were obtained before
      exercise, immediately after and 1 h, 1 day and 1 week later to determine by PCR
      the mtDNA/nuclear DNA (nDNA) ratio (a marker of mtDNA content) and the expression
      of the peroxisome proliferator-activated receptor-gammacoactivator-1alpha (PGC
      1alpha) mRNA and the amount of reactive oxygen species produced during exercise
      was estimated from total V'o2. RESULTS: Skeletal muscle mtDNA/nDNA fell
      significantly after exercise above the LT both in controls and in patients with
      COPD, but the changes were greater in those with COPD. These changes correlated
      with production of reactive oxygen species, increases in manganese superoxide
      dismutase and PGC-1alpha mRNA and returned to baseline values 1 week later. This
      pattern of response was also observed, albeit minimised, in patients exercising
      below the LT. CONCLUSIONS: In patients with COPD, exercise enhances the decrease
      in mtDNA content of skeletal muscle and the expression of PGC-1alpha mRNA seen in
      healthy subjects, probably due to oxidative stress.

PMID- 21097817
TI  - Who bears the costs of occupational asthma?

PMID- 21097818
TI  - What's nice about the new NICE guideline?

PMID- 21097819
TI  - Use of cardiovascular magnetic resonance for risk stratification in chronic heart
      failure: prognostic value of late gadolinium enhancement in patients with non
      ischaemic dilated cardiomyopathy.
AB  - OBJECTIVE: Owing to its variable clinical course, risk stratification is of
      paramount importance in non-ischaemic dilated cardiomyopathy (DCM). The goal of
      this study was to investigate the long-term prognostic significance of late
      gadolinium enhancement (LGE) as detected by contrast-enhanced cardiovascular
      magnetic resonance (CE-CMR) in patients with DCM. DESIGN: Observational cohort
      study. Setting University hospital. PATIENTS: 184 consecutive patients with DCM.
      MEASUREMENTS: CE-CMR was performed on a 1.5 T clinical scanner. Presence, extent
      and patterns of LGE were determined by two independent observers. OUTCOME
      MEASURES: Patients were followed for the composite end point of cardiac death,
      hospitalisation for decompensated heart failure, or appropriate implantable
      cardioverter defibrillator discharge for a mean+/-SEM of 685+/-30 days. RESULTS:
      LGE was detected in 72/184 patients (39%) and was associated with a lower left
      ventricular (LV) ejection fraction (31% (20.9-42.2%) vs 44% (33.1-50.9%),
      p<0.001), higher LV end-diastolic volume index (133 (116-161) ml/m(2) vs 109
      (92.7-137.6) ml/m(2), p<0.001) and higher LV mass (80 (67.1-94.8) g/m(2) vs 65.8
      (55.2-82.9) g/m(2), p<0.001). Patients in whom LGE was present were more likely
      to experience the composite end point (15/72 vs 6/112, p=0.002). Receiver
      operating characteristic curve analysis revealed a LGE of >4.4% of LV mass as
      optimal discriminator for the composite end point. When entered into multivariate
      Cox regression analysis, LGE retained its independent predictive value, yielding
      an associated HR of 3.4 (95% CI 1.26 to 9). CONCLUSION: The presence of LGE in
      this large DCM patient cohort is associated with pronounced LV remodelling,
      functional impairment and an adverse outcome. Further research is necessary to
      determine whether these findings will aid the clinical management of DCM
      patients.

PMID- 21097820
TI  - Performance of the ASSIGN cardiovascular disease risk score on a UK cohort of
      patients from general practice.
AB  - OBJECTIVE: To evaluate the performance of ASSIGN against the Framingham equations
      for predicting 10 year risk of cardiovascular disease in a UK cohort of patients
      from general practice and to make the evaluation comparable to an independent
      evaluation of QRISK on the same cohort. DESIGN: Prospective open cohort study.
      Setting 288 practices from England and Wales contributing to The Health
      Improvement Network (THIN) database. PARTICIPANTS: Patients registered with 288
      UK practices for some period between January 1995 and March 2006. The number of
      records available was 1,787,169. MAIN OUTCOME MEASURES: First diagnosis of
      myocardial infarction, coronary heart disease, stroke and transient ischaemic
      attacks recorded. Methods We implemented the Anderson Framingham Coronary Heart
      Disease and Stroke models, ASSIGN, and a more recent Framingham Cox proportional
      hazards model and analysed their calibration and discrimination. RESULTS:
      Calibration showed that all models tested over-estimated risk particularly for
      men. ASSIGN showed better discrimination with higher AUROC (0.756/0.792 for
      men/women), D statistic (1.35/1.58 for men/women), and R2(30.47%/37.39% for
      men/women). The performance of ASSIGN was comparable to that of QRISK on the same
      cohort. Models agreed on 93-97% of categorical (high/lower) risk assessments and
      when they disagreed, ASSIGN was often closer to the estimated Kaplan-Meier
      incidence. ASSIGN also provided a steeper gradient of deprivation and
      discriminated between those with and without recorded family history of CVD. The
      estimated incidence was twice/three times as high for women/men with a recorded
      family history of CVD. CONCLUSIONS: For systematic CVD risk assessment all models
      could usefully be applied, but ASSIGN improved on the gradient of deprivation and
      accounted for recorded family history whereas the Framingham equations did not.
      However, all models display relatively low specificity and sensitivity. An
      additional conclusion is that the recording of family history of CVD in primary
      care databases needs to improve given its importance in risk assessment.

PMID- 21097821
TI  - Effect of short-term NSAID use on echocardiographic parameters in elderly people:
      a population-based cohort study.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an
      increased risk of heart failure. NSAIDs inhibit the synthesis of renal
      prostaglandin, which results in a higher total blood volume, cardiac output and
      preload. The association between recent start of NSAIDs in elderly people and
      echocardiographic parameters was investigated. METHODS: In the Rotterdam Study, a
      population-based cohort study, the effect of NSAIDs on left ventricular end
      systolic dimension, left ventricular end-diastolic dimension, fractional
      shortening and left ventricular systolic function was studied in all participants
      for whom an echocardiogram was available (n=5307). NSAID use was categorised as
      current NSAID use on the date of echocardiography, past use and never used before
      echocardiography during the study period. Current use was divided into short-term
      NSAID use (<= 14 days) and long-term NSAID use (> 14 days). Associations between
      drug exposure and echocardiographic measurements were assessed using linear and
      logistic regression analyses. RESULTS: Current NSAID use for < 14 days was
      associated with a significantly higher left ventricular end-systolic dimension
      (+1.74 mm, 95% CI 0.20 to 3.28), left ventricular end-diastolic dimension (+3.69
      mm, 95% CI 1.08 to 6.31) and significantly lower fractional shortening (-6.03%,
      95% CI -9.81% to -2.26%) compared with non-users. Current NSAID use for > 14 days
      was associated with a higher left end-diastolic dimension (+1.96 mm, 95% CI 0.82
      to 3.11) but there was no change in the other echocardiographic parameters.
      CONCLUSION: This study is the first to investigate the association between NSAIDs
      and echocardiographic parameters and suggests that there is a transient effect of
      short-term use of NSAIDs on the left ventricular dimension and function of the
      heart.

PMID- 21097822
TI  - A chronic high-cholesterol diet paradoxically suppresses hepatic CYP7A1
      expression in FVB/NJ mice.
AB  - Cholesterol 7alpha-hydroxylase (CYP7A1) encodes for the rate-limiting step in the
      conversion of cholesterol to bile acids in the liver. In response to acute
      cholesterol feeding, mice upregulate CYP7A1 via stimulation of the liver X
      receptor (LXR) alpha. However, the effect of a chronic high-cholesterol diet on
      hepatic CYP7A1 expression in mice is unknown. We demonstrate that chronic
      cholesterol feeding (0.2% or 1.25% w/w cholesterol for 12 weeks) in FVB/NJ mice
      results in a >60% suppression of hepatic CYP7A1 expression associated with a >2
      fold increase in hepatic cholesterol content. In contrast, acute cholesterol
      feeding induces a >3-fold upregulation of hepatic CYP7A1 expression. We show that
      chronic, but not acute, cholesterol feeding increases the expression of hepatic
      inflammatory cytokines, tumor necrosis factor (TNF)alpha, and interleukin (IL)
      1beta, which are known to suppress hepatic CYP7A1 expression. Chronic cholesterol
      feeding also results in activation of the mitogen activated protein (MAP)
      kinases, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase
      (ERK). Furthermore, we demonstrate in vitro that suppression of CYP7A1 by
      TNFalpha and IL-1beta is dependent on JNK and ERK signaling. We conclude that
      chronic high-cholesterol feeding suppresses CYP7A1 expression in mice. We propose
      that chronic cholesterol feeding induces inflammatory cytokine activation and
      liver damage, which leads to suppression of CYP7A1 via activation of JNK and ERK
      signaling pathways.

PMID- 21097826
TI  - Editor's choice. When clarity is sacrificed for cleverness.

PMID- 21097824
TI  - Trends in the epidemiology of multiple sclerosis in Greater Hobart, Tasmania:
      1951 to 2009.
AB  - BACKGROUND: Hobart, Tasmania, has been the site of two major studies of multiple
      sclerosis (MS) frequency, in 1951-1961 and 1971-1981. Since then, there have been
      no studies of MS frequency in Hobart. METHODS: Using a prevalent cohort of 226
      cases in 2001 and 265 in 2009, the authors undertook a two-stage survey of MS
      frequency in Hobart. Combined with the published data from the two preceding
      studies, the authors conducted a time-trend analysis of MS epidemiology over 1951
      2009. RESULTS: The age-standardised prevalence in 2001 was 96.6/100 000, and
      99.6/100 000 in 2009, a significant increase from the 1961 prevalence of 32.5/100
      000 (p<0.001). Female prevalence increased over each time point; male prevalence
      increased between 1961 and 2001 but was unchanged thereafter. Incidence over 2001
      2009 was 3.7/100 000, significantly increased from the 1951-1961 incidence of
      2.2/100 000 (p=0.004), though the majority of this was between 1951-1961 and 1971
      1981. Mortality fell by half from 2.4/100 000 in 1951-1959 to 1.0/100 000 in 2001
      2009-this decreased mortality and an older cohort contribute to the increase in
      prevalence. Neither prevalence (p=0.48) nor incidence (p=0.18) sex ratios changed
      significantly between 1951 and 2009. CONCLUSIONS: Between 1951 and 2009, the age
      standardised prevalence of MS in Hobart increased threefold, and the incidence
      nearly doubled. Part of the increase in prevalence was due to an increased
      longevity, decreased mortality and increased incidence. Differences in patterns
      by birthplace may be explained by the Australian assisted-migration programme of
      1945-1981. These data do not demonstrate the strong and significant changes in
      sex ratio observed elsewhere.

PMID- 21097823
TI  - Regulation of fat specific protein 27 by isoproterenol and TNF-alpha to control
      lipolysis in murine adipocytes.
AB  - The lipid droplet-associated fat specific protein 27 (FSP27) suppresses lipolysis
      and thereby enhances triglyceride accumulation in adipocytes. We and others have
      recently found FSP27 to be a remarkably short-lived protein (half-life, 15 min)
      due to its rapid ubiquitination and proteasomal degradation. Thus, we tested the
      hypothesis that lipolytic agents such as tumor necrosis factor-alpha (TNF-alpha)
      and isoproterenol modulate FSP27 levels to regulate FFA release. Consistent with
      this concept, we showed that the lipolytic actions of TNF-alpha, interleukin
      1beta (IL-1beta), and IFN-gamma are accompanied by marked decreases in FSP27
      expression and lipid droplet size in mouse adipocytes. Similar depletion of FSP27
      using short interfering RNA (siRNA) mimicked the lipolysis-enhancing effect of
      TNF-alpha, while maintaining stable FSP27 levels using expression of
      hemagglutinin epitope-tagged FSP27 blocked TNF-alpha-mediated lipolysis. In
      contrast, we show the robust lipolytic action of isoproterenol is paradoxically
      associated with increases in FSP27 levels and a delayed degradation rate
      corresponding to decreased ubiquitination. This catecholamine-mediated increase
      in FSP27 abundance, probably a feedback mechanism for restraining excessive
      lipolysis by catecholamines, is mimicked by forskolin or 8-bromo-cAMP treatment
      and is prevented by the protein kinase A (PKA) inhibitor KT5720 or by PKA
      depletion using siRNA. Taken together, these data identify the regulation of
      FSP27 as an important intermediate in the mechanism of lipolysis in adipocytes in
      response to TNF-alpha and isoproterenol.

PMID- 21097827
TI  - Animal models of neurological disease: are there any babies in the bathwater?

PMID- 21097828
TI  - Loss of vision.
AB  - Visual loss is not uncommon and many patients end up seeing neurologists because
      of it. There is a long list of possible causes but in most patients visual loss
      is associated with visual field loss. This means that for practical purposes the
      differential diagnosis can usually be narrowed down to a manageable shortlist by
      consideration of where in the visual pathway the lesion is likely to be, along
      with the time course of the visual loss. This article provides a practical
      approach to the diagnosis and appropriate investigation of such patients,
      dividing them into four groups: those in whom vision is lost transiently,
      acutely, subacutely (i.e., days to weeks) and over a longer time frame (months to
      years). In addition, there is a discussion of those patients in whom visual loss
      is not obviously accompanied by any visual field loss.

PMID- 21097829
TI  - The dorsal root ganglion under attack: the acquired sensory ganglionopathies.
AB  - Acquired sensory ganglionopathies--or sensory neuronopathies--are a rare type of
      peripheral neuropathy characterised by damage to the sensory nerve cell bodies in
      the dorsal root ganglia. Subacute or chronic in onset, sensory ganglionopathies
      typically present with a non-length dependent pattern of large fibre sensory
      loss. The causes of this distinct clinical picture include paraneoplastic
      syndromes, immune mediated diseases, infections, as well as drug, toxin and
      excess vitamin exposure. Here we discuss the clinical and pathological features
      of acquired sensory ganglionopathies and focus on a practical approach to their
      diagnosis and management.

PMID- 21097830
TI  - The incompetence of competency assessments in neurology.

PMID- 21097831
TI  - Work based assessments are part of the solution (but only a part), not part of
      the problem.

PMID- 21097832
TI  - Get rid of your stethoscope!

PMID- 21097833
TI  - But a neurosurgeon: after the third gin and tonic.

PMID- 21097834
TI  - A treatable cause for a painful movement disorder.

PMID- 21097835
TI  - The dark side: a year as clinical director (or 'medical management without
      coronary spasm...').

PMID- 21097836
TI  - The bare essentials. Neuro-oncology.

PMID- 21097837
TI  - Prediction of extubation outcome in infants using the tension time index.
AB  - OBJECTIVE: Approximately one-third of ventilated infants fail extubation. The
      objective of this study was to determine whether assessment of the load relative
      to the capacity of respiratory muscles by measurement of the tension time index
      (TTI) successfully predicted extubation outcome in infants. DESIGN: Prospective
      study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Twenty
      ventilated infants, with a median gestational age of 31 (range 24-39) weeks, were
      studied at a median postnatal age of 2.5 (range 1-37) days. INTERVENTIONS: The
      diaphragm tension time index (TTdi) was derived from measurements of
      transdiaphragmatic pressure using a dual-pressure transducer tipped catheter. The
      respiratory muscle tension time index (TTmus) was derived from non-invasive
      airway pressure measurements. Measurements were made within the 6 h prior to
      extubation. MAIN OUTCOME MEASURES: Extubation failure was defined as the need for
      reintubation within 48 h of extubation. RESULTS: Five infants failed extubation;
      their median TTdi (p=0.001) and TTmus (p=0.001) were significantly higher than
      those of the successfully extubated infants. A TTdi of >0.15 and a TTmus of >0.18
      were 100% sensitive and 100% specific in predicting extubation failure
      CONCLUSION: In ventilated infants, invasive and non-invasive measurements of the
      TTI could provide an accurate prediction of extubation outcome.

PMID- 21097839
TI  - Chorioamnionitis, lung function and bronchopulmonary dysplasia in prematurely
      born infants.
AB  - OBJECTIVE: To determine whether prematurely born infants exposed to
      chorioamnionitis compared to those not exposed have poorer lung function and are
      more likely to develop severe bronchopulmonary dysplasia (BPD). DESIGN: Results
      were analysed from consecutive infants born at <33 weeks gestation with placental
      histology results and lung function measurement results on days 2 and/or 7 after
      birth and/or at 36 weeks postmenstrual age (PMA). SETTING: Tertiary neonatal
      intensive care unit. PATIENTS: 120 infants with a median gestational age of 29
      (range 23-32) weeks were studied, 76 (63%) developed BPD and 41 (34%) had been
      exposed to chorioamnionitis and/or funisitis. INTERVENTIONS: Chorioamnionitis was
      diagnosed histologically. MAIN OUTCOME MEASURES: Lung function was assessed by
      measurement of lung volume and compliance and resistance of the respiratory
      system. If the infants remained oxygen dependent beyond 28 days, they were
      diagnosed at 36 weeks PMA to have mild BPD (no longer oxygen dependent), moderate
      BPD (required less than 30% oxygen) or severe BPD (required more than 30% oxygen
      and/or positive pressure support). RESULTS: No significant differences were found
      in the lung function results between the chorioamnionitis and non
      chorioamnionitis groups at any postnatal age. There was no significant
      relationship between chorioamnionitis and the occurrence or severity of BPD.
      Regression analysis demonstrated BPD was significantly related only to birth
      weight, gestational age and use of surfactant. CONCLUSION: In prematurely born
      infants, routinely exposed to antenatal steroids and postnatal surfactant,
      chorioamnionitis was not associated with worse lung function or more severe BPD.

PMID- 21097838
TI  - Acute physiological effects of packed red blood cell transfusion in preterm
      infants with different degrees of anaemia.
AB  - OBJECTIVE: The safe lower limit of haematocrit or haemoglobin that should trigger
      a red blood cell (RBC) transfusion has not been defined. The objective of this
      study was to examine the physiological effects of anaemia and compare the acute
      responses to transfusion in preterm infants who were transfused at higher or
      lower haematocrit thresholds. METHODS: The authors studied 41 preterm infants
      with birth weights 500-1300 g, who were enrolled in a clinical trial comparing
      high ('liberal') and low ('restrictive') haematocrit thresholds for transfusion.
      Measurements were performed before and after a packed RBC transfusion of 15
      ml/kg, which was administered because the infant's haematocrit had fallen below
      the threshold defined by study protocol. Haemoglobin, haematocrit, RBC count,
      reticulocyte count, lactic acid and erythropoietin were measured before and after
      transfusion using standard methods. Cardiac output was measured by
      echocardiography. Oxygen consumption was determined using indirect calorimetry.
      Systemic oxygen transport and fractional oxygen extraction were calculated.
      RESULTS: Systemic oxygen transport rose in both groups following transfusion.
      Lactic acid was lower after transfusion in both groups. Oxygen consumption did
      not change significantly in either group. Cardiac output and fractional oxygen
      extraction fell after transfusion in the low haematocrit group only. CONCLUSIONS:
      These study's results demonstrate no acute physiological benefit of transfusion
      in the high haematocrit group. The fall in cardiac output with transfusion in the
      low haematocrit group shows that these infants had increased their cardiac output
      to maintain adequate tissue oxygen delivery in response to anaemia and,
      therefore, may have benefitted from transfusion.

PMID- 21097840
TI  - Two-year outcomes from very low birthweight infants in a geographically defined
      population across 10 years, 1993-2002: comparing 1993-1997 with 1998-2002.
AB  - AIM: To determine the prevalence and nature of disability at 2 years of age in
      infants born from 1993 to 2002 with a birth weight of <1500 g. METHODS: A
      prospective cohort analysis of all eight neonatal units in East Anglia, UK using
      a single database. Local paediatricians assessed children at 2 years of age using
      the Health Status Questionnaire. Data were analysed using SPSS v 9 and MSAccess
      97. RESULTS: 97% of the 1850 survivors were assessed at 2 years. 21% had mild
      disability, 10.8% moderate and 8.6% severe. There was no evidence of an increased
      rate of disability despite survival rates increasing from 75% in 1993 to 89% in
      2002. There was an increased trend in survival of infants of <28 weeks' gestation
      from 17% to 21% (p=0.08), and the overall rate of moderate to severe disability
      decreased significantly from 35% to 28% (p<0.01). There was a decreasing trend in
      the number of infants with cerebral palsy (6% vs 4%). There was also a decrease
      in the numbers of infants with blindness, hydrocephalus or a hearing impairment.
      Follow-up rates decreased from 99% to 94.5%. Analysis of those lost to follow-up
      revealed they were of higher gestation and birth weight. CONCLUSION: There was no
      evidence of an increased rate of disability despite improved survival rates over
      the two time periods. The rate of blindness decreased, probably reflecting
      earlier treatment of retinopathy of prematurity. This study demonstrates that
      although follow-up remains a challenge, rates of over 90% are achievable.

PMID- 21097841
TI  - The MARCKS protein plays a critical role in phosphatidylinositol 4,5-bisphosphate
      metabolism and directed cell movement in vascular endothelial cells.
AB  - The MARCKS protein (myristoylated alanine-rich C kinase substrate) is an actin-
      and calmodulin-binding protein that is expressed in many mammalian tissues. The
      role of MARCKS in endothelial signaling responses is incompletely understood. We
      found that siRNA-mediated knockdown of MARCKS in cultured endothelial cells
      abrogated directed cell movement in a wound healing assay. We used biochemical
      and cell imaging approaches to explore the role of MARCKS in endothelial signal
      transduction pathways activated by insulin. Insulin treatment of vascular
      endothelial cells promoted the dose- and time-dependent phosphorylation of
      MARCKS. Cell imaging and hydrodynamic approaches revealed that MARCKS is targeted
      to plasmalemmal caveolae and undergoes subcellular translocation in response to
      insulin. Insulin treatment promoted an increase in levels of the signaling
      phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) in plasmalemmal
      caveolae. The insulin-stimulated increase in caveolar PIP(2) was blocked by siRNA
      mediated knockdown of MARCKS, as determined using both biochemical assays and
      imaging studies using FRET-based PIP(2) biosensors. The critical role of PIP(2)
      in MARCKS responses was explored by examining the PIP(2)- and actin-binding
      proteins Arp2/3 and N-WASP. Insulin promoted the rapid and robust phosphorylation
      of both N-WASP and Arp2/3, but these phosphorylation responses were markedly
      attenuated by siRNA-mediated MARCKS knockdown. Moreover, MARCKS knockdown
      effectively abrogated N-WASP activation in response to insulin, as determined
      using a FRET-based N-WASP activity biosensor. Taken together, these studies show
      that MARCKS plays a key role in insulin-dependent endothelial signaling to PIP(2)
      and is a critical determinant of actin assembly and directed cell movement in the
      vascular endothelium.

PMID- 21097842
TI  - Oxidative inactivation of the lipid phosphatase phosphatase and tensin homolog on
      chromosome ten (PTEN) as a novel mechanism of acquired long QT syndrome.
AB  - The most common cause of cardiac side effects of pharmaco-therapy is acquired
      long QT syndrome, which is characterized by abnormal cardiac repolarization and
      most often caused by direct blockade of the cardiac potassium channel human ether
      a-go-go-related gene (hERG). However, little is known about therapeutic compounds
      that target ion channels other than hERG. We have discovered that arsenic
      trioxide (As(2)O(3)), a very potent antineoplastic compound for the treatment of
      acute promyelocytic leukemia, is proarrhythmic via two separate mechanisms: a
      well characterized inhibition of hERG/I(Kr) trafficking and a poorly understood
      increase of cardiac calcium currents. We have analyzed the latter mechanism in
      the present study using biochemical and electrophysiological methods. We find
      that oxidative inactivation of the lipid phosphatase PTEN by As(2)O(3) enhances
      cardiac calcium currents in the therapeutic concentration range via a PI3Kalpha
      dependent increase in phosphatidylinositol 3,4,5-triphosphate (PIP(3))
      production. In guinea pig ventricular myocytes, even a modest reduction in PTEN
      activity is sufficient to increase cellular PIP(3) levels. Under control
      conditions, PIP(3) levels are kept low by PTEN and do not affect calcium current
      amplitudes. Based on pharmacological experiments and intracellular infusion of
      PIP(3), we propose that in guinea pig ventricular myocytes, PIP(3) regulates
      calcium currents independently of the protein kinase Akt along a pathway that
      includes a secondary oxidation-sensitive target. Overall, our report describes a
      novel form of acquired long QT syndrome where the target modified by As(2)O(3) is
      an intracellular signaling cascade.

PMID- 21097844
TI  - Long-term proton pump inhibitor administration worsens atrophic corpus gastritis
      and promotes adenocarcinoma development in Mongolian gerbils infected with
      Helicobacter pylori.
AB  - BACKGROUND: We investigated whether corpus atrophic gastritis worsens in
      Mongolian gerbils (MGs) after long-term administration of proton pump inhibitor
      (PPI). MGs are an excellent model for studying Helicobacter pylori-related
      gastritis and adenocarcinoma. METHODS: MGs were separated into four groups (n
      =15/group); H pylori (ATCC43504) was inoculated into the OPZ(omeprazole)+Hp (H
      pylori) and Hp groups, a PPI (OPZ) was administered to the OPZ+Hp and OPZ groups
      and the control group received no treatment. MGs had access to food containing
      omeprazole (100 mg/kg body weight/day) for 6 months, after which their stomachs
      were removed and cut into nine sections (six sections in the fundus and three
      sections in the antrum). Corpus atrophy was evaluated by the absence of parietal
      cells in the six sections in the fundus. First, we calculated a percentage of the
      area devoid of parietal cells in each haematoxylin and eosin-stained section, and
      then we scored the degree of atrophy by adding the percentages of the six
      sections. A full score was 600. RESULTS: Neutrophilic and lymphoid infiltrates
      were greater in the OPZ+Hp group than in the other groups. The corpus atrophy
      score in the OPZ+Hp group was significantly higher than that in the Hp group (p <
      0.0048, Student t test). Significantly more adenocarcinomas were found in the
      OPZ+Hp (60%) than in the Hp (7%) group animals. CONCLUSION: Long-term PPI
      administration promotes development of adenocarcinoma, which is associated with
      the progression of atrophic corpus gastritis in MGs infected with H pylori.

PMID- 21097843
TI  - Early endosomal antigen 1 (EEA1) is an obligate scaffold for angiotensin II
      induced, PKC-alpha-dependent Akt activation in endosomes.
AB  - Akt/protein kinase B (PKB) activation/phosphorylation by angiotensin II (Ang II)
      is a critical signaling event in hypertrophy of vascular smooth muscle cells
      (VSMCs). Conventional wisdom asserts that Akt activation occurs mainly in plasma
      membrane domains. Recent evidence that Akt activation may take place within
      intracellular compartments challenges this dogma. The spatial identity and
      mechanistic features of these putative signaling domains have not been defined.
      Using cell fractionation and fluorescence methods, we demonstrate that the early
      endosomal antigen-1 (EEA1)-positive endosomes are a major site of Ang II-induced
      Akt activation. Akt moves to and is activated in EEA1 endosomes. The expression
      of EEA1 is required for phosphorylation of Akt at both Thr-308 and Ser-473 as
      well as for phosphorylation of its downstream targets mTOR and S6 kinase, but not
      for Erk1/2 activation. Both Akt and phosphorylated Akt (p-Akt) interact with
      EEA1. We also found that PKC-alpha is required for organizing Ang II-induced,
      EEA1-dependent Akt phosphorylation in VSMC early endosomes. EEA1 expression
      enables PKC-alpha phosphorylation, which in turn regulates Akt upstream signaling
      kinases, PDK1 and p38 MAPK. Our results indicate that PKC-alpha is a necessary
      regulator of EEA1-dependent Akt signaling in early endosomes. Finally, EEA1 down
      regulation or expression of a dominant negative mutant of PKC-alpha blunts Ang II
      induced leucine incorporation in VSMCs. Thus, EEA1 serves a novel function as an
      obligate scaffold for Ang II-induced Akt activation in early endosomes.

PMID- 21097845
TI  - CFTR transcription defects in pancreatic sufficient cystic fibrosis patients with
      only one mutation in the coding region of CFTR.
AB  - BACKGROUND: Patients with cystic fibrosis (CF) manifest a multisystem disease due
      to deleterious mutations in each gene encoding the cystic fibrosis transmembrane
      conductance regulator (CFTR). However, the role of dysfunctional CFTR is
      uncertain in individuals with mild forms of CF (ie, pancreatic sufficiency) and
      mutation in only one CFTR gene. METHODS: Eleven pancreatic sufficient (PS) CF
      patients with only one CFTR mutation identified after mutation screening (three
      patients), mutation scanning (four patients) or DNA sequencing (four patients)
      were studied. Bi-directional sequencing of the coding region of CFTR was
      performed in patients who had mutation screening or scanning. If a second CFTR
      mutation was not identified, CFTR mRNA transcripts from nasal epithelial cells
      were analysed to determine if any PS-CF patients harboured a second CFTR mutation
      that altered RNA expression. RESULTS: Sequencing of the coding regions of CFTR
      identified a second deleterious mutation in five of the seven patients who
      previously had mutation screening or mutation scanning. Five of the remaining six
      patients with only one deleterious mutation identified in the coding region of
      one CFTR gene had a pathologic reduction in the amount of RNA transcribed from
      their other CFTR gene (8.4-16% of wild type). CONCLUSIONS: These results show
      that sequencing of the coding region of CFTR followed by analysis of CFTR
      transcription could be a useful diagnostic approach to confirm that patients with
      mild forms of CF harbour deleterious alterations in both CFTR genes.

PMID- 21097846
TI  - Tricellulin is expressed in autotypic tight junctions of peripheral myelinating
      Schwann cells.
AB  - Autotypic tight junctions are formed by tight junction-like structures in three
      regions of myelinating Schwann cells, the paranodal loops, Schmidt-Lanterman
      incisures, and outer/inner mesaxons, and various tight junction molecules,
      including claudin-19 and junctional adhesion molecule (JAM)-C. Our findings
      demonstrate the identification and subcellular distribution of a novel
      tricellular tight junction protein, tricellulin (TRIC), in the autotypic tight
      junctions of mouse myelinating Schwann cells, compared with the autotypic
      adherens junction protein E-cadherin and the autotypic tight junction protein JAM
      C, which are expressed in the paranodal loops, Schmidt-Lanterman incisures, and
      mesaxons. In real-time RT-PCR, the expression level of TRIC mRNA was about 10
      fold higher in the sciatic nerve than in the spinal cord or cerebrum. In
      immunostaining, TRIC signals were completely restricted to the peripheral nervous
      system (PNS) and strongly concentrated at the paranodal loops, Schmidt-Lanterman
      incisures, and mesaxons of myelinating Schwann cells. In addition, TRIC was
      expressed in the thin region of the paranode and there was a gap between TRIC and
      the Na+ channel. Furthermore, TRIC was more distally located from the node than E
      cadherin and was colocalized with JAM-C. It is possible that TRIC may be a
      component to maintain the integrity for PNS myelin function and morphology. This
      manuscript contains online supplemental material at http://www.jhc.org. Please
      visit this article online to view these materials.

PMID- 21097849
TI  - Contextual control over task-set retrieval.
AB  - Contextual cues signaling task likelihood or the likelihood of task repetition
      are known to modulate the size of switch costs. We follow up on the finding by
      Leboe, Wong, Crump, and Stobbe (2008) that location cues predictive of the
      proportion of switch or repeat trials modulate switch costs. Their design
      employed one cue per task, whereas our experiment employed two cues per task,
      which allowed separate assessment of modulations to the cue-repetition benefit, a
      measure of lower level cue-encoding processes, and to the task-alternation cost,
      a measure of higher level processes representing task-set information. We
      demonstrate that location information predictive of switch proportion modulates
      performance at the level of task-set representations. Furthermore, we demonstrate
      that contextual control occurs even when subjects are unaware of the associations
      between context and switch likelihood. We discuss the notion that contextual
      information provides rapid, unconscious control over the extent to which prior
      task-set representations are retrieved in the service of guiding online
      performance.

PMID- 21097848
TI  - A brief introduction to the use of event-related potentials in studies of
      perception and attention.
AB  - Because of the precise temporal resolution of electrophysiological recordings,
      the event-related potential (ERP) technique has proven particularly valuable for
      testing theories of perception and attention. Here, I provide a brief tutorial on
      the ERP technique for consumers of such research and those considering the use of
      human electrophysiology in their own work. My discussion begins with the basics
      regarding what brain activity ERPs measure and why they are well suited to reveal
      critical aspects of perceptual processing, attentional selection, and cognition,
      which are unobservable with behavioral methods alone. I then review a number of
      important methodological issues and often-forgotten facts that should be
      considered when evaluating or planning ERP experiments.

PMID- 21097850
TI  - Is desynchrony tolerance adaptable in the perceptual organization of speech?
AB  - Speech signal components that are desynchronized from the veridical temporal
      pattern lose intelligibility. In contrast, audiovisual presentations with large
      desynchrony in visible and audible speech streams are perceived without loss of
      integration. Under such conditions, the limit of desynchrony that permits
      audiovisual integration is also adaptable. A new project directly investigated
      the potential for adaptation to consistent desynchrony with unimodal auditory
      sine-wave speech. Listeners transcribed sentences that are highly intelligible,
      with veridical temporal properties. Desynchronized variants were created by
      leading or lagging the tone analog of the second formant relative to the rest of
      the tones composing the sentences, in 50-msec steps, ranging from 250-msec lead
      to 250-msec lag. In blocked trials, listeners only tolerated desynchronies <50
      msec, and exhibited no gain in intelligibility to consistent desynchrony.
      Unimodal auditory and bimodal audiovisual forms of perceptual integration
      evidently exhibit different temporal characteristics, an indication of distinct
      perceptual functions.

PMID- 21097851
TI  - Timing divided attention.
AB  - Visual attention can be divided over multiple objects or locations. However,
      there is no single theoretical framework within which the effects of dividing
      attention can be interpreted. In order to develop such a model, here we
      manipulated the stage of visual processing at which attention was divided, while
      simultaneously probing the costs of dividing attention on two dimensions. We show
      that dividing attention incurs dissociable time and precision costs, which depend
      on whether attention is divided during monitoring or during access. Dividing
      attention during monitoring resulted in progressively delayed access to attended
      locations as additional locations were monitored, as well as a one-off precision
      cost. When dividing attention during access, time costs were systematically lower
      at one of the accessed locations than at the other, indicating that divided
      attention during access, in fact, involves rapid sequential allocation of
      undivided attention. We propose a model in which divided attention is understood
      as the simultaneous parallel preparation and subsequent sequential execution of
      multiple shifts of undivided attention. This interpretation has the potential to
      bring together diverse findings from both the divided-attention and saccade
      preparation literature and provides a framework within which to integrate the
      broad spectrum of divided-attention methodologies.

PMID- 21097852
TI  - Masked singleton effects.
AB  - In the present study, we tested whether visual singletons remaining outside
      awareness are processed. Singletons differ by at least one feature from their
      more homogeneous neighbors. Here, we used backward masking to prevent awareness
      of shape singleton primes (Experiments 1-4) or color singleton primes (Experiment
      5). Masked singleton primes nonetheless produced a congruence effect: Congruent
      singletons indicating the location of subsequent visible targets facilitated
      responses, in comparison with incongruent singletons at positions away from the
      targets. This congruence effect was found with singletons defined by feature
      presence or feature absence. It was at least partly due to attentional capture by
      singletons remaining outside of the participants' awareness. Results are
      discussed in light of theories pertaining to singleton effects and masked-priming
      effects.

PMID- 21097853
TI  - Unexpected changes in direction of motion attract attention.
AB  - Under some circumstances, moving objects capture attention. Whether a change in
      the direction of a moving object attracts attention is still unexplored. We
      investigated this using a continuous tracking task. In Experiment 1, four grating
      patches changed smoothly and semirandomly in their positions and orientations,
      and observers attempted to track the orientations of two of them. After the
      stimuli disappeared, one of the two target gratings was queried and observers
      reported its orientation; hence direction of the gratings' motion across the
      screen was an irrelevant feature. Despite the irrelevance of its motion, when the
      nonqueried grating had collided with an invisible boundary within the last 200
      msec of the trial, accuracy reporting the queried grating was worse than when it
      had not. Attention was likely drawn by the unexpected nature of these changes in
      direction of motion, since the effect was eliminated when the boundaries were
      visible (Experiment 2). This tendency for unexpected motion changes to attract
      attention has important consequences for the monitoring of objects in everyday
      environments.

PMID- 21097854
TI  - Attentional capture by motion onsets is modulated by perceptual load.
AB  - The onset of motion captures attention during visual search even if the motion is
      not task relevant, which suggests that motion onsets capture attention in a
      stimulus-driven manner. However, we have recently shown that stimulus-driven
      attentional capture by abruptly appearing objects is attenuated under conditions
      of high perceptual load. In the present study, we examined the influence of
      perceptual load on attentional capture by another type of dynamic stimulus: the
      onset of motion. Participants searched for a target letter through briefly
      presented low- and high-load displays. On each trial, two irrelevant flankers
      also appeared, one with a motion onset and one that was static. Flankers defined
      by a motion onset captured attention in the low-load but not in the high-load
      displays. This modulation of capture in high-load displays was not the result of
      overall lengthening of reaction times (RTs) in this condition, since search for a
      single low-contrast target lengthened RTs but did not influence capture. These
      results, together with those of previous studies, suggest that perceptual load
      can modulate attentional capture by dynamic stimuli.

PMID- 21097855
TI  - Perceptual load modulates the processing of distractors presented at task
      irrelevant locations during the attentional blink.
AB  - The distribution of attention in both space and time is critical for processing
      our dynamic environment. Studies of spatial attention suggest that the
      distribution of attention is decreased when the perceptual load of a task
      increases, resulting in decreased processing of task-irrelevant distractors.
      Studies of the attentional blink (AB) suggest that the temporal distribution of
      attention also influences distractor processing, such that distractor processing
      increases during the AB relative to outside the AB (Jiang & Chun, 2001). Two
      experiments are reported in which the extent to which the difficulty of the first
      target task (T1) modulates the processing of task-irrelevant distractors during
      the AB was tested. To investigate this issue, both the first and second target
      tasks (T1 and T2) required identifying a central stimulus that was flanked by low
      load or high-load distractors. Consistent with previous studies of the AB, there
      was evidence of more distractor processing during the AB than outside the AB.
      Critically, however, the interference caused by distractors presented
      simultaneously with T2 during the AB was reduced when T1 perceptual load was high
      relative to when it was low. These results suggest that increasing T1 perceptual
      load decreases distractor processing during the AB and that perceptual processes
      influence both the temporal and spatial distribution of attention.

PMID- 21097856
TI  - Still another confounded face in the crowd.
AB  - Experiments using schematic faces developed by Ohman (Ohman, Lundqvist, &
      Esteves, 2001) seem to document an anger-superiority effect, although we have
      come to question these experiments. Our work shows that the low-level features of
      these schematic faces interact with the face's surround to produce effects that
      have been attributed to facial affect. Using relatively neutral faces that
      preserved the feature and surround spatial relationships of angry and happy
      schematic faces, we produced reaction times (RTs) that were indistinguishable
      from those found with angry and happy faces. We also found that the target face's
      position within the crowd determined the magnitude of the advantage for angry
      faces as well as for relatively affect-neutral faces. Removing the facial
      surround reduces the advantage for angry faces, largely by improving performance
      on happy faces. There was an apparent small advantage for angry features without
      a surround. Ohman faces avoid the problems associated with modified grayscale
      faces only to introduce an equally troubling confound.

PMID- 21097857
TI  - Does feature similarity facilitate attentional selection?
AB  - Object-based attention enables us to simultaneously select and report two
      features from the same visual object. Does feature-based attention contribute
      similarly to visual selection? In the present study, we investigated the
      concurrent discrimination of two motion fields with a divided attention paradigm.
      We found that dual-task performance improved when the two fields conformed to a
      continuous optic flow, consistent with "object-based" selection. However, we
      found no such improvement when the two motion fields were merely similar, as
      would have been expected from "feature-based" selection. Therefore, feature
      similarity does not facilitate attentional selection in the same way as belonging
      to the same object does.

PMID- 21097858
TI  - Visual marking survives graphical change if meaning is retained.
AB  - When some distractors (old items) appear before others (new items) in an
      inefficient visual search task, the old items are excluded from the search
      (visual marking). Previous studies have shown that shape changes of static old
      items are sufficient to eliminate this effect when global luminance is
      maintained, suggesting that shape identity must be maintained for successful
      visual marking. It was unclear whether the change in meaning or shape was
      critical, because these changes were confounded in previous studies. The present
      study examined whether consistency in the semantic or the graphical identity of
      old items is critical for visual marking by introducing shape change in the
      absence of meaning change. The results indicated that visual marking survived
      graphical changes in old items as long as their meaning was maintained,
      suggesting that the memory template underlying visual marking represents the
      semantic identity of old items.

PMID- 21097859
TI  - Exogenous temporal cues enhance recognition memory in an object-based manner.
AB  - Exogenous attention enhances the perception of attended items in both a space
      based and an object-based manner. Exogenous attention also improves recognition
      memory for attended items in the space-based mode. However, it has not been
      examined whether object-based exogenous attention enhances recognition memory. To
      address this issue, we examined whether a sudden visual change in a task
      irrelevant stimulus (an exogenous cue) would affect participants' recognition
      memory for items that were serially presented around a cued time. The results
      showed that recognition accuracy for an item was strongly enhanced when the
      visual cue occurred at the same location and time as the item (Experiments 1 and
      2). The memory enhancement effect occurred when the exogenous visual cue and an
      item belonged to the same object (Experiments 3 and 4) and even when the cue was
      counterpredictive of the timing of an item to be asked about (Experiment 5). The
      present study suggests that an exogenous temporal cue automatically enhances the
      recognition accuracy for an item that is presented at close temporal proximity to
      the cue and that recognition memory enhancement occurs in an object-based manner.

PMID- 21097860
TI  - The control of stimulus-driven saccades is subject not to central, but to visual
      attention limitations.
AB  - In three experiments, we investigated whether the control of reflexive saccades
      is subject to central attention limitations. In a dual-task procedure, Task 1
      required either unspeeded reporting or ignoring of briefly presented masked
      stimuli, whereas Task 2 required a speeded saccade toward a visual target. The
      stimulus onset asynchrony (SOA) between the two tasks was varied. In Experiments
      1 and 2, the Task 1 stimulus was one or three letters, and we asked how saccade
      target selection is influenced by the number of items. We found (1) longer
      saccade latencies at short than at long SOAs in the report condition, (2) a
      substantially larger latency increase for three letters than for one letter, and
      (3) a latency difference between SOAs in the ignore condition. Broadly, these
      results match the central interference theory. However, in Experiment 3, an
      auditory stimulus was used as the Task 1 stimulus, to test whether the
      interference effects in Experiments 1 and 2 were due to visual instead of central
      interference. Although there was a small saccade latency increase from short to
      long SOAs, this difference did not increase from the ignore to the report
      condition. To explain visual interference effects between letter encoding and
      stimulus-driven saccade control, we propose an extended theory of visual
      attention.

PMID- 21097861
TI  - Binding targets' responses to distractors' locations: distractor response
      bindings in a location-priming task.
AB  - Responses to target stimuli can be encoded together with distracting objects
      accompanying these targets into a single stimulus-response episode or a single
      event file. Repeating any object of such an episode can trigger the response
      encoded in this episode. Hence, repeating a distractor may retrieve the response
      given to the target that was accompanied by this distractor. In the present
      experiments, we analyzed whether the binding of target responses to the
      distractor can be generalized even to the location of a distractor. In two
      experiments, we used a location-based prime-probe task and found that repeating
      the location of a distractor triggered the response to the target that had
      previously been accompanied by a distractor in the repeated location, even if the
      identity of the distractor changed from the prime to the probe.

PMID- 21097862
TI  - Binocular foveation in reading.
AB  - We present a theory of foveation in normal binocular reading. We consider the
      pervasive, nontrivial binocular fixation disparities (FDs) observed in reading
      and relate them to the computational problem of resolving retinal disparities in
      depth perception. We infer that the right eye's fixation being to the right of
      the left eye's in reading promotes binocular fusion in challenging conditions. We
      then show a different (nonfusional) processing advantage for the right eye's
      fixation being to the left of the left eye's in reading conditions in which
      binocular fusion is assured, by modeling the combined influence of foveal
      splitting, contralateral preference, ocular prevalence, and fixation disparity.
      This synthesis of anatomically grounded research in different aspects of visual
      processing produces a theory of foveation in reading that matches current data
      and makes testable predictions.

PMID- 21097863
TI  - Visual perception in fencing: do the eye movements of fencers represent their
      information pickup?
AB  - The present study examined whether results of athletes' eye movements while they
      observe fencing attacks reflect their actual information pickup by comparing
      these results with others gained with temporal and spatial occlusion and cuing
      techniques. Fifteen top-ranking expert fencers, 15 advanced fencers, and 32 sport
      students predicted the target region of 405 fencing attacks on a computer
      monitor. Results of eye movement recordings showed a stronger foveal fixation on
      the opponent's trunk and weapon in the two fencer groups. Top-ranking expert
      fencers fixated particularly on the upper trunk. This matched their performance
      decrements in the spatial occlusion condition. However, when the upper trunk was
      occluded, participants also shifted eye movements to neighboring body regions.
      Adding cues to the video material had no positive effects on prediction
      performance. We conclude that gaze behavior does not necessarily represent
      information pickup, but that studies applying the spatial occlusion paradigm
      should also register eye movements to avoid underestimating the information
      contributed by occluded regions.

PMID- 21097864
TI  - Auditory temporal cues can modulate visual representational momentum.
AB  - In representational momentum (RM), the final position of a moving target is
      mislocalized in the direction of motion. Here, the effect of a concurrent sound
      on visual RM was demonstrated. A visual stimulus moved horizontally and
      disappeared at unpredictable positions. A complex tone without any motion cues
      was presented continuously from the beginning of the visual motion. As compared
      with a silent condition, the RM magnitude increased when the sound lasted longer
      than and decreased when it did not last as long as the visual motion. However,
      the RM was unchanged when a brief complex tone was presented before or after the
      target disappeared (Experiment 2) or when the onset of the long-lasting sound was
      not synchronized with that of the visual motion (Experiments 3 and 4). These
      findings suggest that visual motion representation can be modulated by a sound if
      the visual motion information is firmly associated with the auditory information.

PMID- 21097865
TI  - Temporal order judgment criteria are affected by synchrony judgment sensitivity.
AB  - Synchrony perception for audio-visual stimulus pairs is typically studied by
      using temporal order judgment (TOJ) or synchrony judgment (SJ) tasks. Research
      has shown that estimates of the point of subjective simultaneity (PSS) obtained
      using these two methods do not necessarily correspond. Here, we investigate the
      hypothesis that the PSS estimate obtained in a TOJ task is shifted in the
      direction of the most sensitive part of the synchrony judgment curve, as obtained
      in an SJ task. The results confirm that criterion shifts in the TOJ task move the
      PSS toward regions of the audio-visual temporal interval continuum where
      discriminations are most sensitive.

PMID- 21097866
TI  - Redundant spoken labels facilitate perception of multiple items.
AB  - Because of the strong associations between verbal labels and the visual objects
      that they denote, hearing a word may quickly guide the deployment of visual
      attention to the named objects. We report six experiments in which we
      investigated the effect of hearing redundant (noninformative) object labels on
      the visual processing of multiple objects from the named category. Even though
      the word cues did not provide additional information to the participants, hearing
      a label resulted in faster detection of attention probes appearing near the
      objects denoted by the label. For example, hearing the word chair resulted in
      more effective visual processing of all of the chairs in a scene relative to
      trials in which the participants attended to the chairs without actually hearing
      the label. This facilitation was mediated by stimulus typicality. Transformations
      of the stimuli that disrupted their association with the label while preserving
      the low-level visual features eliminated the facilitative effect of the labels.
      In the final experiment, we show that hearing a label improves the accuracy of
      locating multiple items matching the label, even when eye movements are
      restricted. We posit that verbal labels dynamically modulate visual processing
      via top-down feedback--an instance of linguistic labels greasing the wheels of
      perception.

PMID- 21097867
TI  - Conversational role influences speech imitation.
AB  - This study assessed the impact of a conscious imitation goal on phonetic
      convergence during conversational interaction. Twelve pairs of unacquainted
      talkers participated in a conversational task designed to elicit between-talker
      repetitions of the same lexical items. To assess the degree to which the talkers
      exhibited phonetic convergence during the conversational task, these repetitions
      were used to elicit perceptual similarity judgments provided by separate sets of
      listeners. In addition, perceptual measures of phonetic convergence were compared
      with measures of articulation rates and vowel formants. The sex of the pair of
      talkers and a talker's role influenced the degree of phonetic convergence, and
      perceptual judgments of phonetic convergence were not consistently related to
      individual acoustic-phonetic attributes. Therefore, even with a conscious
      imitative goal, situational factors were shown to retain a strong influence on
      phonetic form in conversational interaction.

PMID- 21097868
TI  - Hemispheric differences in specificity effects in talker identification.
AB  - In the visual domain, Marsolek and colleagues (1999, 2008) have found support for
      two dissociable and parallel neural subsystems underlying object and shape
      recognition: an abstract-category subsystem that operates more effectively in the
      left cerebral hemisphere (LH), and a specific-exemplar subsystem that operates
      more effectively in the right cerebral hemisphere (RH). Evidence of this
      asymmetry has been observed in priming specificity for linguistic (words,
      pseudoword forms) and nonlinguistic (objects) stimuli. In the auditory domain,
      the authors previously found hemispheric asymmetries in priming effects for
      linguistic (spoken words) and nonlinguistic (environmental sounds) stimuli. In
      the present study, the same asymmetrical pattern was observed in talker
      identification by means of two long-term repetition-priming experiments. Both
      experiments consisted of a familiarization phase and a final talker
      identification test phase, using sentences as stimuli. The results showed that
      specificity effects (an advantage for same-sentence priming, relative to
      different-sentence priming) emerged when the target stimuli were presented to the
      left ear (RH), but not when the target stimuli were presented to the right ear
      (LH). Taken together, this consistent asymmetrical pattern of data from both
      domains-visual and auditory-may be indicative of a more general property of the
      human perceptual processing system. Theoretical implications are discussed.

PMID- 21097869
TI  - Rhythmic context modulates foreperiod effects.
AB  - Two experiments examined hypotheses about the roles of probabilistic uncertainty
      and rhythmic context on attentional preparation as reflected by choice response
      times (RTs) to the final tone of auditory sequences. Nonisochronous sequences
      with tone timings either arranged metrically or scrambled were linked with one of
      three different sequence-final time intervals, or foreperiods (FPs), which varied
      randomly from trial to trial. Two primary results emerged. First, RTs were faster
      to target tones ending metrical rhythms than to targets ending scrambled rhythms.
      Second, metrical contexts elicited RTs that increased with FP duration, whereas
      scrambled contexts elicited RTs that often decreased with FP duration, despite
      equivalent variability of time intervals in metrical and scrambled contexts. The
      results suggest that time relations implied by metrical rhythms systematically
      modulate preparatory responses to sequence-final FPs.

PMID- 21097870
TI  - Updating and feature overwriting in short-term memory for timbre.
AB  - Previous research has demonstrated a potent, stimulus-specific form of
      interference in short-term auditory memory. This effect has been interpreted in
      terms of interitem confusion and grouping, but the present experiments suggested
      that interference might be a feature-specific phenomenon. Participants compared
      standard and comparison tones over a 10-sec interval and were required to
      determine whether they differed in timbre. A single interfering distractor tone
      was presented either 50 msec or 8 sec after the offset of the standard
      (Experiment 1) or 2 sec prior to its onset (Experiment 2). The distractor varied
      in the number of features it shared with the standard and comparison, and this
      proved critical, since performance on the task was greatly impaired when the
      distractor either consisted of novel, unshared features (Experiment 1) or
      contained the distinguishing feature of the comparison tone (Experiments 1 and
      2). These findings were incompatible with earlier accounts of forgetting but were
      fully explicable by the recent timbre memory model, which associates interference
      in short-term auditory memory with an "updating" process and feature overwriting.
      These results suggest similarities with the mechanisms that underlie forgetting
      in verbal short-term memory.

PMID- 21097871
TI  - Differential context effects between sweet tastes and smells.
AB  - "Sweet" smells and tastes are perceptually similar, and physiological data
      indicate some commonality of central processing. However, sweet tastes and sweet
      smells do not provide interchangeable contexts in psychophysical experiments. The
      same sweet tastes are perceived as less intense when stronger sweet tastes are
      present, and they are perceived as more intense when weaker sweet tastes are
      present, as with sweet smells. However, complementary sets of sweet tastes and
      smells (e.g., weak sweet tastes, strong sweet smells) do not eliminate these
      differential context effects (DCEs). The present experiments examined, first,
      whether DCEs between sweet tastes and smells arise because of differences between
      odors and tastes in the way that sweetness scales with intensity as concentration
      rises, and, second, whether DCEs may be smaller for sweet tastes and smells, when
      contrasted with sweet tastes and nonsweet smells. The findings were clear: DCEs
      were consistently present, suggesting they are independent of perceptual
      similarity. These results imply that DCEs are probably not psychological in
      origin or centrally based; rather, they may have a subcortical locus.

PMID- 21097873
TI  - Costs of occupational asthma in the UK.
AB  - OBJECTIVES: To estimate the social costs of occupational asthma in the UK.
      METHODS: A desk-top approach using cost-of-illness methodology was employed,
      defining direct and indirect lifetime costs for six scenarios: a male and a
      female worker each exposed to isocyanates, latex and biocides (eg,
      glutaraldehyde) or flour. The numbers of new cases annually in each industry were
      estimated from Survey of Work-related and Occupational Respiratory Disease
      (SWORD) data. The main outcome measure was the current value total working
      lifetime costs of new cases annually for each scenario. RESULTS: Assuming 209 new
      cases of occupational asthma in the six scenarios in the year 2003, the present
      value total lifetime costs were estimated to be L25.3-27.3 million (2004 prices).
      Grossing up for all estimated cases of occupational asthma in the UK in 2003,
      this came to L70-100 million. About 49% of these costs were borne by the
      individual, 48% by the state and 3% by the employer. CONCLUSIONS: The cost to
      society of occupational asthma in the UK is high. Given that the number of newly
      diagnosed cases is likely to be underestimated by at least one-third, these costs
      may be as large as L95-135 million. Each year a new stream of lifetime costs will
      be added as a newly diagnosed cohort is identified. Approaches to reduce the
      burden of occupational asthma have a strong economic justification. However, the
      economic burden falls on the state and the individual, not on the employer. The
      incentive for employers to act is thus weak.

PMID- 21097874
TI  - Characterization of an interferon-stimulated response element (ISRE) in the Il23a
      promoter.
AB  - We have demonstrated previously that IFN-gamma plays a protective role in the
      initiation of chronic intestinal inflammation through attenuation of Toll-like
      receptor-mediated IL-23 induction in macrophages. Here, an interferon-stimulated
      response element (ISRE) is identified in a region of conserved nucleotide
      sequences in the Il23a promoter. This ISRE mediated, in part, Il23a promoter
      induction by LPS and inhibition of LPS-induced activity by IFN-gamma. LPS and IFN
      gamma recruit interferon regulatory factors (IRFs) to the Il23a ISRE in murine
      bone marrow-derived macrophages (BMMs). Functionally, IRF-1 is a negative
      regulator of Il23a in LPS-stimulated BMMs. IRF-1(-/-) BMMs demonstrated enhanced
      LPS-induced Il23a expression compared with WT BMMs. Moreover, IRF-1 deficiency
      resulted in prolonged occupancy of RelA on the Il23a promoter. Consequently, IRF
      1(-/-) mice were more susceptible to colonic injury by trinitrobenzenesulfonic
      acid, and IL-10/IRF-1 double-deficient (IL-10/IRF-1(-/-)) mice demonstrated more
      severe colonic inflammation compared with IL-10(-/-) mice. The severity of
      colitis in both models correlated with increased colonic IL-23. CD11b(+) lamina
      propria mononuclear cells, comprising predominantly macrophages, were identified
      as the major source of IL-23 in colitis-prone mice. Basal and heat-killed
      Escherichia coli-stimulated levels of Il23a were increased in IL-10/IRF-1(-/-)
      compared with WT and IL-10(-/-) colonic CD11b(+) lamina propria mononuclear
      cells. In conclusion, these experiments characterize IRF-ISRE interactions on the
      Il23a promoter, which have in vivo relevance as a homeostatic checkpoint in
      chronic intestinal inflammation.

PMID- 21097876
TI  - Goals of care among hospitalized patients: a validation study.
AB  - Our objective was to validate 6 literature-derived goals of care by analyzing
      open-ended and closed-ended responses about goals of care from a previous study
      of hospitalized patients. Eight clinicians categorized patients' open-ended
      articulations of their goals of care using a literature-derived framework and
      then compared those categorizations to patients' own closed-ended selections of
      their most important goal of care. Clinicians successfully categorized patients'
      open-ended responses using the literature-derived framework 83.5% of the time,
      and their categorizations matched patients' closed-ended most important goal of
      care 87.8% of the time. Goals that did not fit within the literature-derived
      framework all pertained to the goal of understanding a patient's diagnosis or
      prognosis; this seventh potential goal can be added to the literature-derived
      framework of 6 goals of care.

PMID- 21097875
TI  - The catalytic aspartate is protonated in the Michaelis complex formed between
      trypsin and an in vitro evolved substrate-like inhibitor: a refined mechanism of
      serine protease action.
AB  - The mechanism of serine proteases prominently illustrates how charged amino acid
      residues and proton transfer events facilitate enzyme catalysis. Here we present
      an ultrahigh resolution (0.93 A) x-ray structure of a complex formed between
      trypsin and a canonical inhibitor acting through a substrate-like mechanism. The
      electron density indicates the protonation state of all catalytic residues where
      the catalytic histidine is, as expected, in its neutral state prior to the
      acylation step by the catalytic serine. The carboxyl group of the catalytic
      aspartate displays an asymmetric electron density so that the O(delta2)-C(gamma)
      bond appears to be a double bond, with O(delta2) involved in a hydrogen bond to
      His-57 and Ser-214. Only when Asp-102 is protonated on O(delta1) atom could a
      density functional theory simulation reproduce the observed electron density. The
      presence of a putative hydrogen atom is also confirmed by a residual mF(obs) -
      DF(calc) density above 2.5 sigma next to O(delta1). As a possible functional role
      for the neutral aspartate in the active site, we propose that in the substrate
      bound form, the neutral aspartate residue helps to keep the pK(a) of the
      histidine sufficiently low, in the active neutral form. When the histidine
      receives a proton during the catalytic cycle, the aspartate becomes
      simultaneously negatively charged, providing additional stabilization for the
      protonated histidine and indirectly to the tetrahedral intermediate. This novel
      proposal unifies the seemingly conflicting experimental observations, which were
      previously seen as either supporting the charge relay mechanism or the neutral
      pK(a) histidine theory.

PMID- 21097877
TI  - A single infliximab infusion vs corticosteroids for acute panuveitis attacks in
      Behcet's disease: a comparative 4-week study.
AB  - OBJECTIVE: To compare a single infusion of the anti-TNF antibody infliximab vs
      CSs for acute panuveitis attacks in Behcet's disease (BD). METHODS: A
      prospective, observational study of patients with panuveitis, who received either
      an infliximab infusion (5 mg/kg, 19 eyes) or high-dose methylprednisolone
      intravenously (1 g/day for 3 days, 8 eyes), or intra-vitreal triamcinolone
      acetonide (4 mg, 8 eyes) at attack's onset. Baseline maintenance therapy remained
      unchanged during the following 30 days. Visual acuity, anterior chamber cells,
      vitreous cells and inflammation of the posterior eye segment were assessed at
      baseline and at Days 1, 7, 14 and 29 (+/-1) post-treatment. RESULTS: While no
      significant differences were noted between i.v. and intra-vitreal CSs, infliximab
      was faster than CSs in decreasing total ocular inflammation scores and fundus
      inflammation scores (P = 0.01 and P < 0.0001 for treatment * time(2) interaction,
      respectively, using generalized estimating equation analysis). Independently of
      time, infliximab was superior to CSs in clearing retinal vasculitis (P < 0.003),
      as well as in resolution of retinitis (P = 0.008) and cystoid macular oedema (P <
      0.007). Moreover, a faster regression of cystoid macular oedema was observed with
      infliximab compared with CSs (P < 0.03). The beneficial effects of the three
      treatment modalities on visual acuity were comparable from baseline to the end of
      follow-up. No side effects were noted with infliximab or methylprednisolone,
      whereas intra-vitreal triamcinolone acetonide caused ocular hypertension in four
      of the eight eyes, requiring surgical intervention in two. CONCLUSION: A single
      infusion of infliximab should always be considered, even as an adjunct therapy,
      for the control of acute panuveitis attacks in BD.

PMID- 21097878
TI  - 3D analysis of facial asymmetry in subjects with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate and compare facial asymmetry in subjects with JIA with
      unilateral, bilateral or no TM joint (TMJ) involvement. METHODS: Eighty-one
      subjects with JIA: 22 with unilateral TMJ involvement (Group 1), 15 with
      bilateral TMJ involvement (Group 2) and 44 with no TMJ involvement (Group 3).
      Panoramic X-rays and three-dimensional (3D) photographs (surface scans) were
      obtained for all subjects. Panoramic X-rays were rated for severity of TMJ
      involvement. For each individual, a spatially detailed facial asymmetry map was
      created from the 3D photograph. Mean and variability of asymmetry were calculated
      for each of the three groups and compared. RESULTS: Distinct patterns of
      asymmetry were found in Groups 1 and 2. With mean asymmetry values up to 3.5 mm,
      Group 1 exhibited a significantly greater amount of asymmetry in a broad band
      along the lower jaw extending from the region of the condyle to the chin than
      Group 2. The mean facial asymmetry (1 S.D.) for each JIA group was 2.3 (0.9), 2.0
      (0.7), 1.7 (0.5) mm for Groups 1, 2 and 3, respectively. CONCLUSION: JIA subjects
      with TMJ involvement displayed patterns of facial asymmetry consistent with the
      destruction of the condylar growth centre, leading to mandibular asymmetry with
      displacement of the bony chin. Facial asymmetry quantification was found to be an
      effective method for assessing both the amount and the localization and spatial
      extent of asymmetry in all 3Ds.

PMID- 21097879
TI  - Patients with polymyositis or dermatomyositis have reduced grip force and health
      related quality of life in comparison with reference values: an observational
      study.
AB  - OBJECTIVES: The aims of this study were to investigate hand function in PM and DM
      patients and compare this with reference values in healthy individuals and also
      to investigate if hand function correlated with activity performance and health
      related quality of life. METHODS: An observational cross-sectional study was
      performed in 18 women and 13 men with PM or DM with established disease. Grip
      force and hand mobility were assessed by Grippit and Escola Paulista de Medicina
      Range of Motion scale. Activity performance was measured with myositis activities
      profile and health-related quality of life by short form-36 (SF-36). RESULTS:
      Women and men with PM and DM with mean disease duration of 6.8 (5.5) years had a
      significantly lower grip force than gender- and age-matched healthy individuals
      (women 71% and men 60%). They also had significantly lower mean values in all
      dimensions of the health-related quality of life instrument SF-36 compared with
      the Swedish population. In patients with PM and DM, the grip force correlated
      significantly with the ability to perform domestic activities. In women with PM
      and DM, the grip force correlated significantly with the health-related quality
      of life dimensions vitality and mental health. There were no significant
      differences between patients with PM and DM regarding grip force, hand mobility,
      activity performance or health-related quality of life. CONCLUSIONS: Patients
      with PM or DM have reduced grip force that could influence activity performance
      and health-related quality of life.

PMID- 21097880
TI  - MPromDb update 2010: an integrated resource for annotation and visualization of
      mammalian gene promoters and ChIP-seq experimental data.
AB  - MPromDb (Mammalian Promoter Database) is a curated database that strives to
      annotate gene promoters identified from ChIP-seq results with the goal of
      providing an integrated resource for mammalian transcriptional regulation and
      epigenetics. We analyzed 507 million uniquely aligned RNAP-II ChIP-seq reads from
      26 different data sets that include six human cell-types and 10 distinct mouse
      cell/tissues. The updated MPromDb version consists of computationally predicted
      (novel) and known active RNAP-II promoters (42,893 human and 48,366 mouse
      promoters) from various data sets freely available at NCBI GEO database. We found
      that 36% and 40% of protein-coding genes have alternative promoters in human and
      mouse genomes and ~40% of promoters are tissue/cell specific. The identified RNAP
      II promoters were annotated using various known and novel gene models.
      Additionally, for novel promoters we looked into other evidences-GenBank mRNAs,
      spliced ESTs, CAGE promoter tags and mRNA-seq reads. Users can search the
      database based on gene id/symbol, or by specific tissue/cell type and filter
      results based on any combination of tissue/cell specificity, Known/Novel,
      CpG/NonCpG, and protein-coding/non-coding gene promoters. We have also integrated
      GBrowse genome browser with MPromDb for visualization of ChIP-seq profiles and to
      display the annotations. The current release of MPromDb can be accessed at
      http://bioinformatics.wistar.upenn.edu/MPromDb/.

PMID- 21097881
TI  - HIT: linking herbal active ingredients to targets.
AB  - The information of protein targets and small molecule has been highly valued by
      biomedical and pharmaceutical research. Several protein target databases are
      available online for FDA-approved drugs as well as the promising precursors that
      have largely facilitated the mechanistic study and subsequent research for drug
      discovery. However, those related resources regarding to herbal active
      ingredients, although being unusually valued as a precious resource for new drug
      development, is rarely found. In this article, a comprehensive and fully curated
      database for Herb Ingredients' Targets (HIT, http://lifecenter.sgst.cn/hit/) has
      been constructed to complement above resources. Those herbal ingredients with
      protein target information were carefully curated. The molecular target
      information involves those proteins being directly/indirectly
      activated/inhibited, protein binders and enzymes whose substrates or products are
      those compounds. Those up/down regulated genes are also included under the
      treatment of individual ingredients. In addition, the experimental condition,
      observed bioactivity and various references are provided as well for user's
      reference. Derived from more than 3250 literatures, it currently contains 5208
      entries about 1301 known protein targets (221 of them are described as direct
      targets) affected by 586 herbal compounds from more than 1300 reputable Chinese
      herbs, overlapping with 280 therapeutic targets from Therapeutic Targets Database
      (TTD), and 445 protein targets from DrugBank corresponding to 1488 drug agents.
      The database can be queried via keyword search or similarity search. Crosslinks
      have been made to TTD, DrugBank, KEGG, PDB, Uniprot, Pfam, NCBI, TCM-ID and other
      databases.

PMID- 21097882
TI  - EcoCyc: a comprehensive database of Escherichia coli biology.
AB  - EcoCyc (http://EcoCyc.org) is a comprehensive model organism database for
      Escherichia coli K-12 MG1655. From the scientific literature, EcoCyc captures the
      functions of individual E. coli gene products; their regulation at the
      transcriptional, post-transcriptional and protein level; and their organization
      into operons, complexes and pathways. EcoCyc users can search and browse the
      information in multiple ways. Recent improvements to the EcoCyc Web interface
      include combined gene/protein pages and a Regulation Summary Diagram displaying a
      graphical overview of all known regulatory inputs to gene expression and protein
      activity. The graphical representation of signal transduction pathways has been
      updated, and the cellular and regulatory overviews were enhanced with new
      functionality. A specialized undergraduate teaching resource using EcoCyc is
      being developed.

PMID- 21097883
TI  - Stoichiometry and affinity for thymine DNA glycosylase binding to specific and
      nonspecific DNA.
AB  - Deamination of 5-methylcytosine to thymine creates mutagenic G . T mispairs,
      contributing to cancer and genetic disease. Thymine DNA glycosylase (TDG) removes
      thymine from these G . T lesions, and follow-on base excision repair yields a G .
      C pair. A previous crystal structure revealed TDG (catalytic domain) bound to
      abasic DNA product in a 2:1 complex, one subunit at the abasic site and the other
      bound to undamaged DNA. Biochemical studies showed TDG can bind abasic DNA with
      1:1 or 2:1 stoichiometry, but the dissociation constants were unknown, as was the
      stoichiometry and affinity for binding substrates and undamaged DNA. We showed
      that 2:1 binding is dispensable for G . U activity, but its role in G . T repair
      was unknown. Using equilibrium binding anisotropy experiments, we show that a
      single TDG subunit binds very tightly to G . U mispairs and abasic (G . AP)
      sites, and somewhat less tightly G . T mispairs. Kinetics experiments show 1:1
      binding provides full G . T activity. TDG binds undamaged CpG sites with
      remarkable affinity, modestly weaker than G . T mispairs, and exhibits
      substantial affinity for nonspecific DNA. While 2:1 binding is observed for large
      excess TDG concentrations, our findings indicate that a single TDG subunit is
      fully capable of locating and processing G . U or G . T lesions.

PMID- 21097884
TI  - Cooperation of RAD51 and RAD54 in regression of a model replication fork.
AB  - DNA lesions cause stalling of DNA replication forks, which can be lethal for the
      cell. Homologous recombination (HR) plays an important role in DNA lesion bypass.
      It is thought that Rad51, a key protein of HR, contributes to the DNA lesion
      bypass through its DNA strand invasion activity. Here, using model stalled
      replication forks we found that RAD51 and RAD54 by acting together can promote
      DNA lesion bypass in vitro through the 'template-strand switch' mechanism. This
      mechanism involves replication fork regression into a Holliday junction ('chicken
      foot structure'), DNA synthesis using the nascent lagging DNA strand as a
      template and fork restoration. Our results demonstrate that RAD54 can catalyze
      both regression and restoration of model replication forks through its branch
      migration activity, but shows strong bias toward fork restoration. We find that
      RAD51 modulates this reaction; by inhibiting fork restoration and stimulating
      fork regression it promotes accumulation of the chicken foot structure, which we
      show is essential for DNA lesion bypass by DNA polymerase in vitro. These results
      indicate that RAD51 in cooperation with RAD54 may have a new role in DNA lesion
      bypass that is distinct from DNA strand invasion.

PMID- 21097885
TI  - Non-B DB: a database of predicted non-B DNA-forming motifs in mammalian genomes.
AB  - Although the capability of DNA to form a variety of non-canonical (non-B)
      structures has long been recognized, the overall significance of these alternate
      conformations in biology has only recently become accepted en masse. In order to
      provide access to genome-wide locations of these classes of predicted structures,
      we have developed non-B DB, a database integrating annotations and analysis of
      non-B DNA-forming sequence motifs. The database provides the most complete list
      of alternative DNA structure predictions available, including Z-DNA motifs,
      quadruplex-forming motifs, inverted repeats, mirror repeats and direct repeats
      and their associated subsets of cruciforms, triplex and slipped structures,
      respectively. The database also contains motifs predicted to form static DNA
      bends, short tandem repeats and homo(purine*pyrimidine) tracts that have been
      associated with disease. The database has been built using the latest releases of
      the human, chimp, dog, macaque and mouse genomes, so that the results can be
      compared directly with other data sources. In order to make the data
      interpretable in a genomic context, features such as genes, single-nucleotide
      polymorphisms and repetitive elements (SINE, LINE, etc.) have also been
      incorporated. The database is accessed through query pages that produce results
      with links to the UCSC browser and a GBrowse-based genomic viewer. It is freely
      accessible at http://nonb.abcc.ncifcrf.gov.

PMID- 21097886
TI  - TRAP binding to the Bacillus subtilis trp leader region RNA causes efficient
      transcription termination at a weak intrinsic terminator.
AB  - The Bacillus subtilis trpEDCFBA operon is regulated by a transcription
      attenuation mechanism controlled by the trp RNA-binding attenuation protein
      (TRAP). TRAP binds to 11 (G/U)AG repeats in the trp leader transcript and
      prevents formation of an antiterminator, which allows formation of an intrinsic
      terminator (attenuator). Previously, formation of the attenuator RNA structure
      was believed to be solely responsible for signaling RNA polymerase (RNAP) to halt
      transcription. However, base substitutions that prevent formation of the
      antiterminator, and thus allow the attenuator structure to form constitutively,
      do not result in efficient transcription termination. The observation that the
      attenuator requires the presence of TRAP bound to the nascent RNA to cause
      efficient transcription termination suggests TRAP has an additional role in
      causing termination at the attenuator. We show that the trp attenuator is a weak
      intrinsic terminator due to low GC content of the hairpin stem and interruptions
      in the U-stretch following the hairpin. We also provide evidence that termination
      at the trp attenuator requires forward translocation of RNA polymerase and that
      TRAP binding to the nascent transcript can induce this activity.

PMID- 21097888
TI  - Trans-cleaving hammerhead ribozymes with tertiary stabilizing motifs: in vitro
      and in vivo activity against a structured viroid RNA.
AB  - Trans-cleaving hammerheads with discontinuous or extended stem I and with
      tertiary stabilizing motifs (TSMs) have been tested previously against short RNA
      substrates in vitro at low Mg(2+) concentration. However, the potential of these
      ribozymes for targeting longer and structured RNAs in vitro and in vivo has not
      been examined. Here, we report the in vitro cleavage of short RNAs and of a 464
      nt highly structured RNA from potato spindle tuber viroid (PSTVd) by hammerheads
      with discontinuous and extended formats at submillimolar Mg(2+). Under these
      conditions, hammerheads derived from eggplant latent viroid and peach latent
      mosaic viroid (PLMVd) with discontinuous and extended formats, respectively,
      where the most active. Furthermore, a PLMVd-derived hammerhead with natural TSMs
      showed activity in vivo against the same long substrate and interfered with
      systemic PSTVd infection, thus reinforcing the idea that this class of ribozymes
      has potential to control pathogenic RNA replicons.

PMID- 21097887
TI  - Direct and indirect effects of H-NS and Fis on global gene expression control in
      Escherichia coli.
AB  - Nucleoid-associated proteins (NAPs) are global regulators of gene expression in
      Escherichia coli, which affect DNA conformation by bending, wrapping and bridging
      the DNA. Two of these--H-NS and Fis--bind to specific DNA sequences and
      structures. Because of their importance to global gene expression, the binding of
      these NAPs to the DNA was previously investigated on a genome-wide scale using
      ChIP-chip. However, variation in their binding profiles across the growth phase
      and the genome-scale nature of their impact on gene expression remain poorly
      understood. Here, we present a genome-scale investigation of H-NS and Fis binding
      to the E. coli chromosome using chromatin immunoprecipitation combined with high
      throughput sequencing (ChIP-seq). By performing our experiments under multiple
      time-points during growth in rich media, we show that the binding regions of the
      two proteins are mutually exclusive under our experimental conditions. H-NS binds
      to significantly longer tracts of DNA than Fis, consistent with the linear spread
      of H-NS binding from high- to surrounding lower-affinity sites; the length of
      binding regions is associated with the degree of transcriptional repression
      imposed by H-NS. For Fis, a majority of binding events do not lead to
      differential expression of the proximal gene; however, it has a significant
      indirect effect on gene expression partly through its effects on the expression
      of other transcription factors. We propose that direct transcriptional regulation
      by Fis is associated with the interaction of tandem arrays of Fis molecules to
      the DNA and possible DNA bending, particularly at operon-upstream regions. Our
      study serves as a proof-of-principle for the use of ChIP-seq for global DNA
      binding proteins in bacteria, which should become significantly more economical
      and feasible with the development of multiplexing techniques.

PMID- 21097889
TI  - PAK1IP1, a ribosomal stress-induced nucleolar protein, regulates cell
      proliferation via the p53-MDM2 loop.
AB  - Cell growth and proliferation are tightly controlled via the regulation of the
      p53-MDM2 feedback loop in response to various cellular stresses. In this study,
      we identified a nucleolar protein called PAK1IP1 as another regulator of this
      loop. PAK1IP1 was induced when cells were treated with chemicals that disturb
      ribosome biogenesis. Overexpression of PAK1IP1 inhibited cell proliferation by
      inducing p53-dependent G1 cell-cycle arrest. PAK1IP1 bound to MDM2 and inhibited
      its ability to ubiquitinate and to degrade p53, consequently leading to the
      accumulation of p53 levels. Interestingly, knockdown of PAK1IP1 in cells also
      inhibited cell proliferation and induced p53-dependent G1 arrest. Deficiency of
      PAK1IP1 increased free ribosomal protein L5 and L11 which were required for
      PAK1IP1 depletion-induced p53 activation. Taken together, our results reveal that
      PAK1IP1 is a new nucleolar protein that is crucial for rRNA processing and plays
      a regulatory role in cell proliferation via the p53-MDM2 loop.

PMID- 21097890
TI  - Database resources of the National Center for Biotechnology Information.
AB  - In addition to maintaining the GenBank(r) nucleic acid sequence database, the
      National Center for Biotechnology Information (NCBI) provides analysis and
      retrieval resources for the data in GenBank and other biological data made
      available through the NCBI Web site. NCBI resources include Entrez, the Entrez
      Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Entrez Gene, the
      NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT,
      Electronic PCR, OrfFinder, Splign, ProSplign, RefSeq, UniGene, HomoloGene,
      ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Cancer Chromosomes, Entrez Genomes and
      related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive,
      Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein
      Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online
      Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals
      (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database
      (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), IBIS,
      Biosystems, Peptidome, OMSSA, Protein Clusters and the PubChem suite of small
      molecule databases. Augmenting many of the Web applications are custom
      implementations of the BLAST program optimized to search specialized data sets.
      All of these resources can be accessed through the NCBI home page at
      www.ncbi.nlm.nih.gov.

PMID- 21097891
TI  - dbDNV: a resource of duplicated gene nucleotide variants in human genome.
AB  - Gene duplications are scattered widely throughout the human genome. A single-base
      difference located in nearly identical duplicated segments may be misjudged as a
      single nucleotide polymorphism (SNP) from individuals. This imperfection is
      undistinguishable in current genotyping methods. As the next-generation
      sequencing technologies become more popular for sequence-based association
      studies, numerous ambiguous SNPs are rapidly accumulated. Thus, analyzing
      duplication variations in the reference genome to assist in preventing false
      positive SNPs is imperative. We have identified >10% of human genes associated
      with duplicated gene loci (DGL). Through meticulous sequence alignments of DGL,
      we systematically designated 1,236,956 variations as duplicated gene nucleotide
      variants (DNVs). The DNV database (dbDNV) (http://goods.ibms.sinica.edu.tw/DNVs/)
      has been established to promote more accurate variation annotation. Aside from
      the flat file download, users can explore the gene-related duplications and the
      associated DNVs by DGL and DNV searches, respectively. In addition, the dbDNV
      contains 304,110 DNV-coupled SNPs. From DNV-coupled SNP search, users observe
      which SNP records are also variants among duplicates. This is useful while ~58%
      of exonic SNPs in DGL are DNV-coupled. Because of high accumulation of ambiguous
      SNPs, we suggest that annotating SNPs with DNVs possibilities should improve
      association studies of these variants with human diseases.

PMID- 21097892
TI  - COMBREX: a project to accelerate the functional annotation of prokaryotic
      genomes.
AB  - COMBREX (http://combrex.bu.edu) is a project to increase the speed of the
      functional annotation of new bacterial and archaeal genomes. It consists of a
      database of functional predictions produced by computational biologists and a
      mechanism for experimental biochemists to bid for the validation of those
      predictions. Small grants are available to support successful bids.

PMID- 21097893
TI  - NCBI GEO: archive for functional genomics data sets--10 years on.
AB  - A decade ago, the Gene Expression Omnibus (GEO) database was established at the
      National Center for Biotechnology Information (NCBI). The original objective of
      GEO was to serve as a public repository for high-throughput gene expression data
      generated mostly by microarray technology. However, the research community
      quickly applied microarrays to non-gene-expression studies, including examination
      of genome copy number variation and genome-wide profiling of DNA-binding
      proteins. Because the GEO database was designed with a flexible structure, it was
      possible to quickly adapt the repository to store these data types. More
      recently, as the microarray community switches to next-generation sequencing
      technologies, GEO has again adapted to host these data sets. Today, GEO stores
      over 20,000 microarray- and sequence-based functional genomics studies, and
      continues to handle the majority of direct high-throughput data submissions from
      the research community. Multiple mechanisms are provided to help users
      effectively search, browse, download and visualize the data at the level of
      individual genes or entire studies. This paper describes recent database
      enhancements, including new search and data representation tools, as well as a
      brief review of how the community uses GEO data. GEO is freely accessible at
      http://www.ncbi.nlm.nih.gov/geo/.

PMID- 21097894
TI  - Concentration-dependent exchange accelerates turnover of proteins bound to double
      stranded DNA.
AB  - The multistep kinetics through which DNA-binding proteins bind their targets are
      heavily studied, but relatively little attention has been paid to proteins
      leaving the double helix. Using single-DNA stretching and fluorescence detection,
      we find that sequence-neutral DNA-binding proteins Fis, HU and NHP6A readily
      exchange with themselves and with each other. In experiments focused on the
      Escherichia coli nucleoid-associated protein Fis, only a small fraction of
      protein bound to DNA spontaneously dissociates into protein-free solution.
      However, if Fis is present in solution, we find that a concentration-dependent
      exchange reaction occurs which turns over the bound protein, with a rate of
      k(exch) = 6 * 10(4) M(-1)s(-1). The bacterial DNA-binding protein HU and the
      yeast HMGB protein NHP6A display the same phenomenon of protein in solution
      accelerating dissociation of previously bound labeled proteins as exchange
      occurs. Thus, solvated proteins can play a key role in facilitating removal and
      renewal of proteins bound to the double helix, an effect that likely plays a
      major role in promoting the turnover of proteins bound to DNA in vivo and,
      therefore, in controlling the dynamics of gene regulation.

PMID- 21097895
TI  - PCDB: a database of protein conformational diversity.
AB  - PCDB (http://www.pcdb.unq.edu.ar) is a database of protein conformational
      diversity. For each protein, the database contains the redundant compilation of
      all the corresponding crystallographic structures obtained under different
      conditions. These structures could be considered as different instances of
      protein dynamism. As a measure of the conformational diversity we use the maximum
      RMSD obtained comparing the structures deposited for each domain. The redundant
      structures were extracted following CATH structural classification and cross
      linked with additional information. In this way it is possible to relate a given
      amount of conformational diversity with different levels of information, such as
      protein function, presence of ligands and mutations, structural classification,
      active site information and organism taxonomy among others. Currently the
      database contains 7989 domains with a total of 36581 structures from 4171
      different proteins. The maximum RMSD registered is 26.7 A and the average of
      different structures per domain is 4.5.

PMID- 21097896
TI  - ANGUSTIFOLIA3 plays roles in adaxial/abaxial patterning and growth in leaf
      morphogenesis.
AB  - Leaf morphogenesis relies on adaxial/abaxial patterning and extensive growth.
      This study investigated the role of ANGUSTIFOLIA3 (AN3) from Arabidopsis thaliana
      in these processes. The an3 mutants produce narrower leaves that contain
      significantly fewer cells than the wild type. We examined the genetic interaction
      between an3 and asymmetric leaves2 (as2), which has a weak adaxial defect. The
      an3 as2 mutants developed trumpet-like leaves and accumulated transcripts of
      abaxially expressed genes at higher levels than an3 and as2. Gene expression
      analyses suggested that an3 altered the expression of a number of genes. Many of
      them were involved in metabolism, and several genes that promote adaxial identity
      cooperatively with as2 were down-regulated. Next, we performed detailed
      developmental analyses to examine the relationship between the narrow-leaf
      phenotype of an3 and leaf polarity. As a result, we showed that AN3 is required
      during a specific phase after an oblong shape is established in early leaf
      primordia. During this phase, the angle of the cell division plane relative to
      the longitudinal axis of the leaf primordium is more variable than in the earlier
      phase where transverse divisions were dominant in both the wild type and an3.
      Correlated with this dynamic change in cell division pattern, the leaf primordium
      became rounder. In an3, mitotic activity was reduced more rapidly than in the
      wild type, causing premature termination of the morphometric change. These
      results suggest that AN3 promotes cell proliferation during a specific
      developmental phase that is also required to correct abaxial/adaxial patterning
      in concert with AS2.

PMID- 21097897
TI  - OsLEA1a, a new Em-like protein of cereal plants.
AB  - Proteins abundant in seeds during the late stages of development, late
      embryogenesis abundant (LEA) proteins, are associated with desiccation tolerance.
      More than 100 of the group I LEA genes, also termed Em genes, have been
      identified from plants, bacteria and animals. The wide distribution indicates the
      functional importance of these genes. In the present study, we characterized a
      novel Em-like gene, OsLEA1a of rice (Oryza sativa). The encoded OsLEA1a protein
      has an N-terminal sequence similar to that of other plant Em proteins but lacks a
      20-mer motif that is the most significant feature of typical Em proteins. The
      location of the sole intron indicates that the second exon of OsLEA1a is the
      mutated product of a typical Em gene. Transcriptome analysis revealed OsLEA1a
      mainly expressed in embryos, with no or only a few transcripts in osmotic stress
      treated vegetative tissues. Structural analysis revealed that the OsLEA1a protein
      adopts high amounts of disordered conformations in solution and undergoes
      desiccation-induced conformational changes. Macromolecular interaction studies
      revealed that OsLEA1a protein interacts with non-reducing sugars and
      phospholipids but not poly-l-lysine. Thus, although the OsLEA1a protein lost its
      20-mer motif, it is still involved in the formation of bioglasses with non
      reducing sugars or plasma membrane. However, the protein does not function as a
      chaperone as do other groups of hydrophilic LEA proteins. The orthologs of the
      OsLEA1a gene had been identified from various grasses but not in dicot plants.
      Genetic analysis indicated that rice OsLEA1a locates at a 193 kb segment in
      chromosome 1 and is conserved in several published cereal genomes. Thus, the
      ancestor of Em-like genes might have evolved after the divergence of monocot
      plants.

PMID- 21097898
TI  - The role of endarterectomy and stenting in the management of carotid artery
      stenosis: a 5-year Delphi survey.
AB  - INTRODUCTION: Ambiguity in the literature concerning potential benefits of
      carotid artery stenting (CAS) as an alternative to carotid endarterectomy (CEA)
      necessitated a 5-year Delphi-type survey, gauging the changing views over this
      period of relevant experts undertaking carotid intervention. METHODS: Delphi
      surveys performed in 2004 and 2009 involved 2 rounds of questions combined with
      feedback of results from the first round between them. The questionnaire was e
      mailed to UK vascular surgeons, neurosurgeons, interventional radiologists, and
      cardiologists. RESULTS: In 2004 and 2009, the second round response rates were
      69% and 51%, respectively. Over 5 years, there was a statistically significant
      reduction in support for ''general anesthesia risk'' and ''contralateral
      occlusion'' as indications for CAS and views that CAS ''increased patient
      satisfaction'' and ''decreased the length of hospital stay.'' Concerning the
      impact of recent trials on the professionals' treatment routines for symptomatic
      and asymptomatic patients with carotid disease, 65.8% and 76.3%, respectively,
      had not changed their overwhelming non-CAS routines, with 32.9% and 19.7% saying
      clinical trial results moved them toward CEA. CONCLUSIONS: A 2009 survey of
      vascular experts found no increase in preference for CAS as a treatment option
      for advanced carotid bifurcation atherosclerosis. This, in combination with the
      lack of change from and indeed move toward the ''gold-standard'' CEA,
      demonstrates a general decline in confidence with CAS.

PMID- 21097899
TI  - Relationship between left and right ventricular ejection fractions in chronic
      advanced systolic heart failure: insights from the BEST trial.
AB  - AIMS: Abnormally low right ventricular ejection fraction (RVEF) is a predictor of
      poor outcomes in chronic heart failure (HF) patients with low left ventricular
      ejection fraction (LVEF). However, little is known about the relationship between
      LVEF and RVEF in these patients. METHODS AND RESULTS: Of the 2707 Beta-blocker
      Evaluation of Survival Trial (BEST) participants with ambulatory chronic HF, New
      York Heart Association class III-IV symptoms, and LVEF <= 35%, 2008 patients had
      gated-equilibrium radionuclide angiographic data on baseline LVEF and RVEF.
      Patients were categorized into quartiles by LVEF >= 29% (n = 507), 23-28% (n =
      513), 17-22% (n = 538), and < 17% (n = 450). Logistic regression models were used
      to determine the association of LVEF quartiles (reference, >= 29%) with
      abnormally low RVEF (<20%). The prevalence of RVEF < 20% for patients with LVEF
      quartiles >= 29, 23-28, 17-22, and < 17% were 3, 6, 15, and 32%, respectively.
      Unadjusted odds ratios [95% confidence intervals (CIs)] for RVEF < 20% (vs. >=
      20%) associated with LVEF quartiles 23-28, 17-22, and < 17% (reference, >= 29%)
      were 2.18 (1.14-4.17; P = 0.018), 6.32 (3.54-11.30; P < 0.001), and 16.67 (9.46
      29.39; P < 0.001), respectively. Respective multivariable-adjusted odds ratios
      (95% CIs) were 1.82 (0.94-3.54; P = 0.076), 4.55 (2.48-8.35; P < 0.001), and
      10.53 (5.70-19.44; P< 0.001), respectively. Heart failure symptoms and signs had
      unadjusted associations with low RVEF, but lacked intrinsic associations.
      CONCLUSION: In patients with advanced systolic HF, LVEF has a strong dose
      dependent relationship with RVEF which is independent of other characteristics,
      and low LVEF is useful as a surrogate marker of abnormally low RVEF in these
      patients.

PMID- 21097900
TI  - Phenotypic and genotypic characterization of influenza virus mutants selected
      with the sialidase fusion protein DAS181.
AB  - BACKGROUND: influenza viruses (IFVs) frequently achieve resistance to antiviral
      drugs, necessitating the development of compounds with novel mechanisms of
      action. DAS181 (Fludase), a sialidase fusion protein, may have a reduced
      potential for generating drug resistance due to its novel host-targeting
      mechanism of action. METHODS: IFV strains B/Maryland/1/59 and A/Victoria/3/75
      (H3N2) were subjected to >30 passages under increasing selective pressure with
      DAS181. The DAS181-selected IFV isolates were characterized in vitro and in mice.
      RESULTS: despite extensive passaging, DAS181-selected viruses exhibited a very
      low level of resistance to DAS181, which ranged between 3- and 18-fold increase
      in EC(50). DAS181-selected viruses displayed an attenuated phenotype in vitro, as
      exhibited by slower growth, smaller plaque size and increased particle to pfu
      ratios relative to wild-type virus. Further, the DAS181 resistance phenotype was
      unstable and was substantially reversed over time upon DAS181 withdrawal. In
      mice, the DAS181-selected viruses exhibited no greater virulence than their wild
      type counterparts. Genotypic and phenotypic analysis of DAS181-selected viruses
      revealed mutations in the haemagglutinin (HA) and neuraminidase (NA) molecules
      and also changes in HA and NA function. CONCLUSIONS: results indicate that
      resistance to DAS181 is minimal and unstable. The DAS181-selected IFV isolates
      exhibit reduced fitness in vitro, likely due to altered HA and NA functions.

PMID- 21097901
TI  - Glucose and weight control in mice with a designed ghrelin O-acyltransferase
      inhibitor.
AB  - Ghrelin is a gastric peptide hormone that stimulates weight gain in vertebrates.
      The biological activities of ghrelin require octanoylation of the peptide on
      Ser(3), an unusual posttranslational modification that is catalyzed by the enzyme
      ghrelin O-acyltransferase (GOAT). Here, we describe the design, synthesis, and
      characterization of GO-CoA-Tat, a peptide-based bisubstrate analog that
      antagonizes GOAT. GO-CoA-Tat potently inhibits GOAT in vitro, in cultured cells,
      and in mice. Intraperitoneal administration of GO-CoA-Tat improves glucose
      tolerance and reduces weight gain in wild-type mice but not in ghrelin-deficient
      mice, supporting the concept that its beneficial metabolic effects are due
      specifically to GOAT inhibition. In addition to serving as a research tool for
      mapping ghrelin actions, GO-CoA-Tat may help pave the way for clinical targeting
      of GOAT in metabolic diseases.

PMID- 21097904
TI  - Evidence of supersolidity in rotating solid helium.
AB  - Supersolidity, the appearance of zero-viscosity flow in solids, was first
      indicated in helium-4 torsional oscillator (TO) experiments. In this apparatus,
      the irrotationality of the superfluid component causes it to decouple from the
      underlying normal solid, leading to a reduction in the resonant period of the TO.
      However, the resonant period may be altered for reasons other than supersolidity,
      such as the temperature dependence of the elastic modulus of solid helium.
      Superimposing rotation onto oscillatory measurements may distinguish between
      supersolidity and classical effects. We performed such simultaneous measurements
      of the TO and the shear modulus, and observed substantial change in the resonant
      period with rotational speed where the modulus remained unchanged. This
      contrasting behavior suggests that the decrease in the TO period is a result of
      supersolidity.

PMID- 21097903
TI  - Arabidopsis type I metacaspases control cell death.
AB  - Metacaspases are distant relatives of animal caspases found in protozoa, fungi,
      and plants. Limited experimental data exist defining their function(s), despite
      their discovery by homology modeling a decade ago. We demonstrated that two type
      I metacaspases, AtMC1 and AtMC2, antagonistically control programmed cell death
      in Arabidopsis. AtMC1 is a positive regulator of cell death and requires
      conserved caspase-like putative catalytic residues for its function. AtMC2
      negatively regulates cell death. This function is independent of the putative
      catalytic residues. Manipulation of the Arabidopsis type I metacaspase regulatory
      module can nearly eliminate the hypersensitive cell death response (HR) activated
      by plant intracellular immune receptors. This does not lead to enhanced pathogen
      proliferation, decoupling HR from restriction of pathogen growth.

PMID- 21097905
TI  - A giant planet around a metal-poor star of extragalactic origin.
AB  - Stars in their late stage of evolution, such as horizontal branch stars, are
      still largely unexplored for planets. We detected a planetary companion around
      HIP 13044, a very metal-poor star on the red horizontal branch, on the basis of
      radial velocity observations with a high-resolution spectrograph at the 2.2-meter
      Max-Planck Gesellschaft-European Southern Observatory telescope. The star's
      periodic radial velocity variation of P = 16.2 days caused by the planet can be
      distinguished from the periods of the stellar activity indicators. The minimum
      mass of the planet is 1.25 times the mass of Jupiter and its orbital semimajor
      axis is 0.116 astronomical units. Because HIP 13044 belongs to a group of stars
      that have been accreted from a disrupted satellite galaxy of the Milky Way, the
      planet most likely has an extragalactic origin.

PMID- 21097906
TI  - A new focus on plant sciences.

PMID- 21097907
TI  - Space science. Massive cost overrun to Webb threatens other NASA missions.

PMID- 21097908
TI  - Marine ecology. Key indicator of ocean health may be flawed.

PMID- 21097909
TI  - Science and society. GM mosquito trial alarms opponents, strains ties in Gates
      funded project.

PMID- 21097911
TI  - Condensed-matter physics. New spin on solid helium bolsters case for bizarre
      flow.

PMID- 21097910
TI  - Research metrics. Handful of U.S. schools claim larger share of output.

PMID- 21097912
TI  - Newsmaker interview: Subra Suresh. A world of changes prepares Subra Suresh to
      tackle change at NSF.

PMID- 21097913
TI  - Russian science: waking from hibernation.

PMID- 21097914
TI  - Interview: Andrei Fursenko. University research should compete with Russian
      Academy, science minister argues. Interview by Daniel Clery.

PMID- 21097902
TI  - Plasticity of animal genome architecture unmasked by rapid evolution of a pelagic
      tunicate.
AB  - Genomes of animals as different as sponges and humans show conservation of global
      architecture. Here we show that multiple genomic features including transposon
      diversity, developmental gene repertoire, physical gene order, and intron-exon
      organization are shattered in the tunicate Oikopleura, belonging to the sister
      group of vertebrates and retaining chordate morphology. Ancestral architecture of
      animal genomes can be deeply modified and may therefore be largely nonadaptive.
      This rapidly evolving animal lineage thus offers unique perspectives on the level
      of genome plasticity. It also illuminates issues as fundamental as the mechanisms
      of intron gain.

PMID- 21097915
TI  - Uncertain future for academy's biology experiment.

PMID- 21097916
TI  - Time to take action on climate communication.

PMID- 21097917
TI  - Overbuilding: overhead revisions.

PMID- 21097918
TI  - Overbuilding: under pressure.

PMID- 21097919
TI  - Overbuilding: doctoral degree surplus.

PMID- 21097920
TI  - Comment on "Single-crystal X-ray structure of 1,3-dimethylcyclobutadiene by
      confinement in a crystalline matrix".
AB  - Legrand et al. (Reports, 16 July 2010, p. 299) reported the experimental
      observation of square-planar and rectangular-bent geometries of 1,3
      dimethylcyclobutadiene (Me(2)CBD) confined within a crystalline matrix. However,
      we found no evidence for the Me(2)CBD formation. We argue that the experimental x
      ray density data are better attributed to the bicyclic beta-lactone intermediate
      where carbon dioxide is covalently bound to cyclobutadiene.

PMID- 21097921
TI  - Comment on "Single-crystal X-ray structure of 1,3-dimethylcyclobutadiene by
      confinement in a crystalline matrix".
AB  - Legrand et al. (Reports, 16 July 2010, p. 299) reported on the photolytic
      reaction of an alpha-pyrone confined in a crystalline matrix. Their structural
      analysis invoked four products: activated precursor, isomeric Dewar beta-lactone,
      and square and rectangular isomers of 1,3-dimethylcyclobutadiene. The reported x
      ray data, however, suggest that all observed structures correspond to only one
      distinct species, the Dewar beta-lactone.

PMID- 21097922
TI  - Overbuilding: boosting school ratings.

PMID- 21097923
TI  - Food safety. Genetically modified salmon and full impact assessment.

PMID- 21097924
TI  - Chemistry. Nanosilver revisited downstream.

PMID- 21097925
TI  - Genetics. Gamma-secretase and human disease.

PMID- 21097926
TI  - Chemistry. Magnetic resonance and microfluidics.

PMID- 21097927
TI  - Microbiology. Topping off a multiscale balancing act.

PMID- 21097928
TI  - Neuroscience. pi = visual cortex.

PMID- 21097929
TI  - Plant and animal sensors of conserved microbial signatures.
AB  - The last common ancestor of plants and animals may have lived 1 billion years
      ago. Plants and animals have occasionally exchanged genes but, for the most part,
      have countered selective pressures independently. Microbes (bacteria, eukaryotes,
      and viruses) were omnipresent threats, influencing the direction of multicellular
      evolution. Receptors that detect molecular signatures of infectious organisms
      mediate awareness of nonself and are integral to host defense in plants and
      animals alike. The discoveries leading to elucidation of these receptors and
      their ligands followed a similar logical and methodological pathway in both plant
      and animal research.

PMID- 21097930
TI  - The uncertainty principle determines the nonlocality of quantum mechanics.
AB  - Two central concepts of quantum mechanics are Heisenberg's uncertainty principle
      and a subtle form of nonlocality that Einstein famously called "spooky action at
      a distance." These two fundamental features have thus far been distinct concepts.
      We show that they are inextricably and quantitatively linked: Quantum mechanics
      cannot be more nonlocal with measurements that respect the uncertainty principle.
      In fact, the link between uncertainty and nonlocality holds for all physical
      theories. More specifically, the degree of nonlocality of any theory is
      determined by two factors: the strength of the uncertainty principle and the
      strength of a property called "steering," which determines which states can be
      prepared at one location given a measurement at another.

PMID- 21097931
TI  - Faster interprotein electron transfer in a [myoglobin, b5] complex with a
      redesigned interface.
AB  - Direct measurements of electron transfer (ET) within a protein-protein complex
      with a redesigned interface formed by physiological partner proteins myoglobin
      (Mb) and cytochrome b(5) (b(5)) reveal interprotein ET rates comparable to those
      observed within the photosynthetic reaction center. Brownian dynamics simulations
      show that Mb in which three surface acid residues are mutated to lysine binds
      b(5) in an ensemble of configurations distributed around a reactive most-probable
      structure. Correspondingly, charge-separation ET from a photoexcited singlet zinc
      porphyrin incorporated within Mb to the heme of b(5) and the follow-up charge
      recombination exhibit distributed kinetics, with median rate constants, k(f)(s) =
      2.1 * 10(9) second(-1) and k(b)(s) = 4.3 * 10(10) second(-1), respectively. The
      latter approaches that for the initial step in photosynthetic charge separation,
      k = 3.3 * 10(11) second(-1).

PMID- 21097932
TI  - Loss of carbon from the deep sea since the Last Glacial Maximum.
AB  - Deep-ocean carbonate ion concentrations ([CO(3)(2-)]) and carbon isotopic ratios
      (delta(13)C) place important constraints on past redistributions of carbon in the
      ocean-land-atmosphere system and hence provide clues to the causes of atmospheric
      CO(2) concentration changes. However, existing deep-sea [CO(3)(2-)]
      reconstructions conflict with one another, complicating paleoceanographic
      interpretations. Here, we present deep-sea [CO(3)(2-)] for five cores from the
      three major oceans quantified using benthic foraminiferal boron/calcium ratios
      since the last glacial period. Combined benthic delta(13)C and [CO(3)(2-)]
      results indicate that deep-sea-released CO(2) during the early deglacial period
      (17.5 to 14.5 thousand years ago) was preferentially stored in the atmosphere,
      whereas during the late deglacial period (14 to 10 thousand years ago), besides
      contributing to the contemporary atmospheric CO(2) rise, a substantial portion of
      CO(2) released from oceans was absorbed by the terrestrial biosphere.

PMID- 21097934
TI  - Interdependence of cell growth and gene expression: origins and consequences.
AB  - In bacteria, the rate of cell proliferation and the level of gene expression are
      intimately intertwined. Elucidating these relations is important both for
      understanding the physiological functions of endogenous genetic circuits and for
      designing robust synthetic systems. We describe a phenomenological study that
      reveals intrinsic constraints governing the allocation of resources toward
      protein synthesis and other aspects of cell growth. A theory incorporating these
      constraints can accurately predict how cell proliferation and gene expression
      affect one another, quantitatively accounting for the effect of translation
      inhibiting antibiotics on gene expression and the effect of gratuitous protein
      expression on cell growth. The use of such empirical relations, analogous to
      phenomenological laws, may facilitate our understanding and manipulation of
      complex biological systems before underlying regulatory circuits are elucidated.

PMID- 21097933
TI  - Structure of the human dopamine D3 receptor in complex with a D2/D3 selective
      antagonist.
AB  - Dopamine modulates movement, cognition, and emotion through activation of
      dopamine G protein-coupled receptors in the brain. The crystal structure of the
      human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R
      specific antagonist eticlopride reveals important features of the ligand binding
      pocket and extracellular loops. On the intracellular side of the receptor, a
      locked conformation of the ionic lock and two distinctly different conformations
      of intracellular loop 2 are observed. Docking of R-22, a D3R-selective
      antagonist, reveals an extracellular extension of the eticlopride binding site
      that comprises a second binding pocket for the aryl amide of R-22, which differs
      between the highly homologous D2R and D3R. This difference provides direction to
      the design of D3R-selective agents for treating drug abuse and other
      neuropsychiatric indications.

PMID- 21097935
TI  - Symbiotic bacterium modifies aphid body color.
AB  - Color variation within populations of the pea aphid influences relative
      susceptibility to predators and parasites. We have discovered that infection with
      a facultative endosymbiont of the genus Rickettsiella changes the insects' body
      color from red to green in natural populations. Approximately 8% of pea aphids
      collected in Western Europe carried the Rickettsiella infection. The infection
      increased amounts of blue-green polycyclic quinones, whereas it had less of an
      effect on yellow-red carotenoid pigments. The effect of the endosymbiont on body
      color is expected to influence prey-predator interactions, as well as
      interactions with other endosymbionts.

PMID- 21097936
TI  - Workplace smoking policies and their association with male employees' smoking
      behaviours: a cross-sectional survey in one company in China.
AB  - OBJECTIVES: The present work sought to evaluate different worksite smoking
      control policies and their associations with employees' smoking behaviours and
      attitudes among Chinese male workers. METHODS: This was a cross-sectional survey
      with a self-administered standardised questionnaire, conducted among seven
      production workplaces of one multinational company in Shanghai in 2008. In total,
      1043 male workers were involved. Current smoking prevalence, daily cigarette
      consumption, quitting intention and their potential association with workplace
      smoking control policies (smoke free or restricted smoking) were measured.
      RESULTS: Current smoking prevalence in workplaces where smoke-free policies had
      been imposed for 3 years was 55.5%, about 18% lower than in workplaces that only
      restricted smoking. Smokers in smoke-free workplaces also smoked 3.4 cigarettes
      less per day, made more quit attempts, were more confident of successfully
      quitting and more willing to accept a company sponsored cessation programme.
      Those patterns declined or were not found among the workplaces where smoking
      control policies had been imposed for 10 years. Smoker quitting intentions were
      not associated with workplace smoking policies regardless of the duration of the
      policies imposed. CONCLUSIONS: A smoke-free workplace policy was found to have a
      significant association with lower smoking prevalence and daily cigarette
      consumption, but not with employee quitting intentions. Restrictive smoking
      policies had no impact on employee smoking behaviours. The impact of workplace
      smoking control policies may vary over time.

PMID- 21097937
TI  - The relationship between temperature and ambulance response calls for heat
      related illness in Toronto, Ontario, 2005.
AB  - BACKGROUND: Concern over the adverse effects of heat on human health has led to
      numerous studies assessing the relationship between heat and mortality. Few
      studies have quantified the impact of heat on morbidity, including ambulance
      response calls. This study describes the association between temperature and
      ambulance response calls for heat-related illness (HRI) in Toronto, Ontario,
      Canada during the summer of 2005. METHODS: Data sources included daily
      temperature, relative humidity and humidex information from Environment Canada,
      and Medical Priority Dispatch System data from Toronto Emergency Medical
      Services. Time series and regression analyses were used to examine the
      relationship between daily temperature and ambulance response calls for HRI
      during the summer (1 June to 31 August) of 2005. RESULTS: In 2005, there were 201
      ambulance response calls for HRI. On average, for every one degree increase in
      maximum temperature ( degrees C) there was a 29% increase in ambulance response
      calls for HRI (p<0.0001). For every one degree increase in mean temperature (
      degrees C) there was a 32% increase in ambulance response calls for HRI
      (p<0.0001). CONCLUSIONS: Given these associations, we urge further exploration of
      ambulance response calls as a source of HRI morbidity data particularly given the
      increasing health concerns associated with climate change.

PMID- 21097938
TI  - The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and
      Coats disease.
AB  - AIM: The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial
      exudative vitreoretinopathy (FEVR) and Coats disease. METHODS: Tissue samples
      were collected for DNA extraction and automated DNA sequencing of the two coding
      exons of FZD4 in both directions. Cases carrying a FZD4 mutation and
      demonstrating extreme disease severity were selected for direct automated
      sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were
      obtained for the purpose of identifying genotype-phenotype correlations. RESULTS:
      68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven
      FZD4 mutations (five missense, three deletions, one insertion, two nonsense) were
      identified. Six of these mutations are novel, and none were found in 346 control
      chromosomes. In 16 cases of Coats disease, one polymorphism combination was found
      in two samples: no mutations were detected. No genotype-phenotype correlation
      emerged. Three severely affected cases with FZD4 mutations failed to show
      additional mutations in the three other FEVR genes. CONCLUSION: The authors
      identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a
      useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in
      FZD4 do not appear to be a common cause of Coats disease.

PMID- 21097939
TI  - A test for mental capacity to request assisted suicide.
AB  - The mental competence of people requesting aid-in-dying is a key issue for the
      how the law responds to cases of assisted suicide. A number of cases from around
      the common law world have highlighted the importance of competence in determining
      whether assistants should be prosecuted, and what they will be prosecuted for.
      Nevertheless, the law remains uncertain about how competence should be tested in
      these cases. This article proposes a test of competence that is based on the
      existing common law but which is tailored to cases of assisted suicide. The test
      will help doctors, other health professionals and lawyers determine whether the
      suicidal person was able to competently request assistance. Such knowledge will
      help to reduce some of the current uncertainty about criminal liability in cases
      of assisted suicide.

PMID- 21097940
TI  - Scientific evidence and best patient care practices should guide the ethics of
      Lyme disease activism.
AB  - Johnson and Stricker published an opinion piece in the Journal of Medical Ethics
      presenting their perspective on the 2008 agreement between the Infectious
      Diseases Society of America (IDSA) and the Connecticut Attorney General with
      regard to the 2006 IDSA treatment guideline for Lyme disease. Their writings
      indicate that these authors hold unconventional views of a relatively common tick
      transmitted bacterial infection caused by the spirochete Borrelia burgdorferi.
      Therefore, it should come as no surprise that their opinions would clash with the
      IDSA's evidence-based guidelines for the diagnosis and treatment of Lyme disease.
      Their allegations of conflict of interest against the IDSA resemble those made
      against the National Institutes of Health, the Food and Drug Administration and
      the Centers for Disease Control and Prevention in 2000, which were found to be
      baseless. It is the responsibility of all physicians and medical scientists to
      stand up to antiscientific, baseless and unethical attacks on those who support
      an evidence-based approach to caring for patients.

PMID- 21097941
TI  - Respecting frailty.
AB  - While the medical treatment of older individuals often results in desirable
      outcomes, indiscriminate use of aggressive treatment at the end-of-life can cause
      paradoxical harm and suffering. Comprehensive assessment and communication can
      help foster decisions that consider the effect of frailty on health outcomes.

PMID- 21097942
TI  - Priority to registered donors on the waiting list for postmortal organs? A
      critical look at the objections.
AB  - It has often been proposed to restrict access to postmortal organs to registered
      donors, or at least to give them priority on the waiting list. Such proposals are
      motivated by considerations of fairness: everyone benefits from the existence of
      a pool of available organs and of an organised system of distributing them and it
      is unfair that people who are prepared to contribute to this public good are
      duped by people who are not. This paper spells out this rationale and goes on to
      discuss the main principled objections that have been brought forward to such
      proposals. The most fundamental objection is that healthcare resources should be
      allocated in accordance with need, not with merit. The reply to this objection is
      that the principle of allocation according to need only holds in cases in which
      the provision of such resources and the fair distribution of the burdens of
      contribution are independently secured, as they are in an obligatory insurance
      system.

PMID- 21097943
TI  - Barriers to, and facilitators of, the prevention of unintentional injury in
      children in the home: a systematic review and synthesis of qualitative research.
AB  - BACKGROUND: This review considers barriers to, and facilitators of, success for
      interventions to reduce unintentional injury to children in the home through
      supply and/or installation of home safety equipment, and looks at risk
      assessments. METHODS: A systematic review of qualitative research. Bibliographic
      databases were searched for studies on interventions to reduce unintentional
      child injury in the home, or on related attitudes and behaviours. Studies were
      quality appraised, findings extracted, and a conceptual framework was developed
      to assess factors affecting the success of interventions. RESULTS: Nine peer
      reviewed journal articles were included. Barriers and facilitators were
      highlighted at organisational, environmental and personal levels. Effective
      provision of safety equipment involves ongoing support with installation and
      maintenance. Take up and success of interventions depends on adjusting
      interventions according to practical limitations and parents' cultural
      expectations. A particular barrier was parents' inability to modify rented or
      shared accommodation. CONCLUSIONS: The review highlights ways in which health
      inequalities affect the take up and success of home safety interventions, and how
      health workers can use this knowledge to facilitate future interventions.

PMID- 21097944
TI  - Approaching the ruptured anterior cruciate ligament.
AB  - Anterior cruciate ligament (ACL) disruptions are common injuries that currently
      hold a fearsome reputation among athletes of all abilities and disciplines.
      Indeed, if the diagnosis is missed at first presentation, it is difficult to
      attribute ongoing instability and recurrent injury to an ACL tear. Classically,
      patients then often improve shortly before repeatedly reinjuring their knee. At
      some point, the knee may lock, necessitating an arthroscopic meniscectomy.
      Tragically, this then hastens the progression of joint arthrosis and the decline
      of the joint function. While the burden of responsibility does not lie solely
      with the junior doctor or the general practitioner, it is often at the first
      consultation that the natural history of this devastating injury is decided. The
      ability to recognise, institute early management and reassure patients with ACL
      tears about the future is an invaluable asset to the non-specialist junior
      doctor. Once diagnosed, the responsibility of advising and further counselling of
      patients with ACL injuries is best left to the orthopaedic knee specialist.
      Family practitioners and emergency room doctors should not feel pressured to
      offer advice on specialist areas such as return to sports without reconstruction
      or indeed the need for reconstruction. Indeed, decisions to return to sports with
      ACL-deficient knees have all too often led to disastrous reinjury events to the
      articular cartilage and/or the menisci.

PMID- 21097945
TI  - Modelling the effects of the weather on admissions to UK trauma units: a cross
      sectional study.
AB  - OBJECTIVE: To assess the relationship between daily trauma admissions and
      observed weather variables, using data from the Trauma Audit and Research Network
      of England and Wales and the UK Meteorological Office. DESIGN: A cross-sectional
      study. SETTING: Twenty-one accident and emergency departments (ED) located across
      England. PARTICIPANTS: All patients arriving at one of the selected ED, with a
      subsequent death, inpatient stay of greater than 3 days, interhospital transfer
      or requiring critical care between 1 January 1996 and 31 December 2006. MAIN
      OUTCOME MEASURES: Daily counts of adult and paediatric trauma admissions.
      RESULTS: Multivariate regression analysis indicated that there were strong
      seasonal trends in paediatric (chi(2) likelihood ratio test p<0.001), and adult
      (p=0.016) trauma admissions. For adults, each rise of 5 degrees C in the maximum
      daily temperature and each additional 2 h of sunshine caused increases in trauma
      admissions of 1.8% and 1.9%. Effects in the paediatric group were considerably
      larger, with similar increases in temperature and hours of sunshine causing
      increases in trauma admissions of 10% and 6%. Each drop of 5 degrees C in the
      minimum daily temperature, eg, due to a severe night time frost, caused adult
      trauma admissions to increase by 3.2%. Also the presence of snow increased adult
      trauma admissions by 7.9%. CONCLUSION: This is the largest study of its kind to
      investigate and quantify the relationship between trauma admissions and the
      weather. The results show clear associations that have direct application for
      planning and resource management in UK ED.

PMID- 21097946
TI  - Simulation of fruit-set and trophic competition and optimization of yield
      advantages in six Capsicum cultivars using functional-structural plant modelling.
AB  - BACKGROUND AND AIMS: Many indeterminate plants can have wide fluctuations in the
      pattern of fruit-set and harvest. Fruit-set in these types of plants depends
      largely on the balance between source (assimilate supply) and sink strength
      (assimilate demand) within the plant. This study aims to evaluate the ability of
      functional-structural plant models to simulate different fruit-set patterns among
      Capsicum cultivars through source-sink relationships. METHODS: A greenhouse
      experiment of six Capsicum cultivars characterized with different fruit weight
      and fruit-set was conducted. Fruit-set patterns and potential fruit sink strength
      were determined through measurement. Source and sink strength of other organs
      were determined via the GREENLAB model, with a description of plant organ weight
      and dimensions according to plant topological structure established from the
      measured data as inputs. Parameter optimization was determined using a
      generalized least squares method for the entire growth cycle. KEY RESULTS AND
      CONCLUSIONS: Fruit sink strength differed among cultivars. Vegetative sink
      strength was generally lower for large-fruited cultivars than for small-fruited
      ones. The larger the size of the fruit, the larger variation there was in fruit
      set and fruit yield. Large-fruited cultivars need a higher source-sink ratio for
      fruit-set, which means higher demand for assimilates. Temporal heterogeneity of
      fruit-set affected both number and yield of fruit. The simulation study showed
      that reducing heterogeneity of fruit-set was obtained by different approaches:
      for example, increasing source strength; decreasing vegetative sink strength,
      source-sink ratio for fruit-set and flower appearance rate; and harvesting
      individual fruits earlier before full ripeness. Simulation results showed that,
      when we increased source strength or decreased vegetative sink strength, fruit
      set and fruit weight increased. However, no significant differences were found
      between large-fruited and small-fruited groups of cultivars regarding the effects
      of source and vegetative sink strength on fruit-set and fruit weight. When the
      source-sink ratio at fruit-set decreased, the number of fruit retained on the
      plant increased competition for assimilates with vegetative organs. Therefore,
      total plant and vegetative dry weights decreased, especially for large-fruited
      cultivars. Optimization study showed that temporal heterogeneity of fruit-set and
      ripening was predicted to be reduced when fruits were harvested earlier.
      Furthermore, there was a 20 % increase in the number of extra fruit set.

PMID- 21097947
TI  - Contrasting dynamics of radial O2-loss barrier induction and aerenchyma formation
      in rice roots of two lengths.
AB  - BACKGROUND AND AIMS: Many wetland species form aerenchyma and a barrier to radial
      O(2) loss (ROL) in roots. These features enhance internal O(2) diffusion to the
      root apex. Barrier formation in rice is induced by growth in stagnant solution,
      but knowledge of the dynamics of barrier induction and early anatomical changes
      was lacking. METHODS: ROL barrier induction in short and long roots of rice
      (Oryza sativa L. 'Nipponbare') was assessed using cylindrical root-sleeving O(2)
      electrodes and methylene blue indicator dye for O(2) leakage. Aerenchyma
      formation was also monitored in root cross-sections. Microstructure of
      hypodermal/exodermal layers was observed by transmission electron microscopy
      (TEM). KEY RESULTS: In stagnant medium, barrier to ROL formation commenced in
      long adventitious roots within a few hours and the barrier was well formed within
      24 h. By contrast, barrier formation took longer than 48 h in short roots. The
      timing of enhancement of aerenchyma formation was the same in short and long
      roots. Comparison of ROL data and subsequent methylene blue staining determined
      the apparent ROL threshold for the dye method, and the dye method confirmed that
      barrier induction was faster for long roots than for short roots. Barrier
      formation might be related to deposition of new electron-dense materials in the
      cell walls at the peripheral side of the exodermis. Histochemical staining
      indicated suberin depositions were enhanced prior to increases in lignin.
      CONCLUSIONS: As root length affected formation of the barrier to ROL, but not
      aerenchyma, these two acclimations are differentially regulated in roots of rice.
      Moreover, ROL barrier induction occurred before histochemically detectable
      changes in putative suberin and lignin deposits could be seen, whereas TEM showed
      deposition of new electron-dense materials in exodermal cell walls, so structural
      changes required for barrier functioning appear to be more subtle than previously
      described.

PMID- 21097948
TI  - Neurobehavioral effects of long-term exposure to pesticides: results from the 4
      year follow-up of the PHYTONER study.
AB  - OBJECTIVE: The aim of the PHYTONER study is to investigate the role of pesticides
      on neurobehavioral performances in French vineyard workers. METHODS: 929 workers
      affiliated to the health insurance system for farmers in the Bordeaux area of
      south-western France were enrolled in the study in 1997-1998. They were contacted
      for a first follow-up in 2001-2003. Participants completed a questionnaire and
      nine neurobehavioral tests. They were classified according to their life-long
      pesticide exposure, as directly exposed, indirectly exposed or non-exposed.
      Educational level, age, sex, alcohol consumption, smoking, psychotropic drug use
      and depressive symptoms were taken into account in the analysis. RESULTS: 614
      subjects were available for investigation at follow-up. Follow-up analysis
      confirmed that the risk of obtaining a low performance on the tests was higher in
      exposed subjects, with ORs ranging from 1.35 to 5.60. Evolution of performances
      over the follow-up period demonstrated that exposed subjects had the worst
      decreases in performance. The risk of having a two-point lower score on the Mini
      Mental State Examination was 2.15 (95% CI 1.18 to 3.94) in exposed subjects.
      CONCLUSION: These results suggest long-term cognitive effects of chronic exposure
      to pesticides and raise the issue of the risk of evolution towards dementia. The
      PHYTONER study is the first to provide prospective data on the natural history of
      neurological disorders associated with pesticide exposure.

PMID- 21097949
TI  - Anatomy laboratory instruction and occupational exposure to formaldehyde.

PMID- 21097950
TI  - Long-term effects on humoral immunity among workers exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - OBJECTIVES: Epidemiological studies have shown inconsistent effects on
      immunological parameters in subjects exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). In this study we investigated changes in humoral immunity and
      prevalence of atopic diseases among workers from a Dutch historical cohort
      occupationally exposed to chlorophenoxy herbicides and contaminants including
      TCDD. METHODS: 45 workers who had been exposed to high levels of TCDD in the past
      and 108 non-exposed workers (39 from the same factory as the exposed subjects
      (internal control group) and 69 from a comparable factory but without TCDD
      exposure (external control group)) were included in the study. Blood
      immunoglobulin (Ig) and complement factor (C) concentrations and specific IgE
      antibodies to a panel of common allergens were measured using quantitative
      nephelometry or ELISA. TCDD plasma levels were measured and back-extrapolated to
      the time of last exposure (TCDDmax) using a one-compartment first order kinetic
      model. RESULTS: A borderline significant negative association between both
      current and predicted TCDD levels and C4 was found in multivariate analyses (beta
      = -0.020; 95% CI = -0.040-0.010 and beta = -0.020; 95% CI = -0.030-0.00,
      respectively). History of eczema was significantly associated with current TCDD
      levels in both crude (OR = 1.5; 95% CI = 1.03-2.2) and adjusted models (OR = 1.7;
      95% CI = 1.08-2.7). CONCLUSIONS: Our results do not support an association
      between TCDD exposure and markers of humoral immunity except possibly C4.
      Interestingly, decreased levels of C4 have been linked to lymphoma risk, which
      provides some support to the putative link between TCDD and non-Hodgkin lymphoma.

PMID- 21097951
TI  - Rushing, distraction, walking on contaminated floors and risk of slipping in
      limited-service restaurants: a case--crossover study.
AB  - OBJECTIVES: This nested case-crossover study examined the association between
      rushing, distraction and walking on a contaminated floor and the rate of
      slipping, and whether the effects varied according to weekly hours worked, job
      tenure and use of slip-resistant shoes. METHODS: At baseline, workers from 30
      limited-service restaurants in the USA reported average work hours, average
      weekly duration of exposure to each transient risk factor and job tenure at the
      current location. Use of slip-resistant shoes was determined. During the
      following 12 weeks, participants reported weekly their slip experience and
      exposures to the three transient exposures at the time of slipping. The case
      crossover design was used to estimate the rate ratios using the Mantel-Haenszel
      estimator for person-time data. RESULTS: Among 396 participants providing
      baseline information, 210 reported one or more slips with a total of 989 slips.
      Rate of slipping was 2.9 times higher when rushing as compared to working at a
      normal pace (95% CI 2.5 to 3.3). Rate of slipping was also significantly
      increased by distraction (rate ratio (RR) 1.7, 95% CI 1.5 to 2.0) and walking on
      a contaminated floor (RR 14.6, 95% CI 12.6 to 17.0). Use of slip-resistant shoes
      decreased the effects of rushing and walking on a contaminated floor. Rate ratios
      for all three transient factors decreased monotonically as job tenure increased.
      CONCLUSION: The results suggest the importance of these transient risk factors,
      particularly floor contamination, on rate of slipping in limited-service
      restaurant workers. Stable characteristics, such as slip-resistant shoes, reduced
      the effects of transient exposures.

PMID- 21097952
TI  - The effects of educational intervention on nutritional behaviour in alcohol
      dependent patients.
AB  - AIMS: To evaluate the nutritional status and the impact of an educational
      intervention on nutritional behaviour in alcohol-dependent patients. METHODS: A
      pre-and post-intervention questionnaire and a follow-up interview were
      administered to 58 patients of a residential alcohol treatment service. RESULTS:
      Females were at lower risk of being overweight than males, even after adjusting
      for amount and preferred type of alcohol beverage. Before intervention, 19%
      consumed 3 meals/day. Following the educational intervention, 22.2% of
      participants improved their knowledge. After 6 months, when 45 patients agreed to
      a telephone interview of whom 80% reported continued abstinence, 70.7% reported
      eating more than 3 meals/day. CONCLUSIONS: Nutritional behaviour of alcohol
      patients after residential treatments improved during follow-up, and it is
      possible that an educational intervention to increase knowledge on healthy
      nutrition style may have contributed.

PMID- 21097953
TI  - The role of membrane properties in Mistic folding and dimerisation.
AB  - Membranes not only provide cellular compartmentalization but influence protein
      behavior and folding by virtue of the multitude of different lipid types. We have
      studied the impact of lipid composition on the folding of the membrane-associated
      protein Mistic from B. subtilis. We use dimerisation via the single Cys3 residue
      as monitor for the degree of correct folding, since mis- or unfolding will expose
      the otherwise buried Cys3. We find great variability in how lipids affect protein
      production and dimerization, ranging from high production and low dimerization
      via increased production and higher dimerization to low production and low
      dimerization. Phosphocholine (PC) vesicles, in particular di-oleoyl-PC, lead to
      the highest production levels. Shorter chain lengths lead to reduced production
      but higher levels of dimerization. Different lipids may promote correct folding
      of Mistic to different extents, mediated by proper hydrophobic matching (attained
      for long-chain but not short-chain PC vesicles) and the existence of a fluid
      phase (the gel phase reduces production as well as dimerization, probably by
      immobilizing Mistic on the surface). The very fact that different lipids have an
      effect indicates that Mistic behaves like a bona fide membrane protein with a
      clear preference for membranes of a certain thickness and flexibility.

PMID- 21097954
TI  - Maternal underweight and the risk of preterm birth and low birth weight: a
      systematic review and meta-analyses.
AB  - BACKGROUND: Despite the current obesity epidemic, maternal underweight remains a
      common occurrence with potential adverse perinatal outcomes. Our objective was to
      determine the relationship between maternal underweight and preterm birth (PTB)
      and low birth weight (LBW) in singleton pregnancies in developing and developed
      countries. METHODS: We followed the MOOSE consensus statement. We searched
      MEDLINE and EMBASE from their inceptions. We included studies that assessed the
      effect of maternal underweight compared with normal weight according to body mass
      index in singleton gestations on our two primary outcomes: PTB (<37 weeks) and
      LBW (<2500 g). Two assessors independently reviewed citations, extracted data and
      assessed quality. RESULTS: A total of 78 studies were included involving 1 025
      794 women. The overall risk of PTB was increased in the cohort studies of
      underweight women [adjusted relative risk (RR) 1.29, 95% confidence interval (CI)
      1.15-1.46], as were the risks of spontaneous PTB (adjusted RR 1.32, 95% CI 1.10
      1.57) and induced PTB (adjusted RR 1.21, 95% CI 1.07-1.36). Underweight women had
      an increased risk of an LBW infant (adjusted RR 1.64, 95% CI 1.38-1.94). In
      developed countries, underweight women had an increased risk of PTB (RR 1.22, 95%
      CI 1.15-1.30) but not in developing countries (RR 0.99, 95% CI 0.67-1.45). In
      both developed and developing countries, underweight women were at increased risk
      of having an LBW infant (RR 1.48, 95% CI 1.29-1.68, and RR 1.52, 95% CI 1.25
      1.85, respectively). CONCLUSIONS: In this systematic review and meta-analyses, we
      determined that singletons born to underweight women have higher risks of PTB
      (overall, spontaneous and induced) and LBW than those born to women with normal
      weight.

PMID- 21097955
TI  - A preliminary examination of the psychometric properties of the Coparenting
      Questionnaire and the Diabetes-Specific Coparenting Questionnaire in families of
      children with type I diabetes.
AB  - OBJECTIVES: To examine the structure and psychometric properties of a general
      childrearing [Coparenting Questionnaire (CQ)] and an adapted Diabetes-Specific
      Coparenting Questionnaire (DCQ) and compare general and diabetes-specific
      coparenting among two-parent families caring for a child with type I diabetes.
      METHODS: Mothers and fathers of children (N=61) aged 8-12 years with type I
      diabetes completed self-report measures of marital functioning, parenting, and
      coparenting, including the CQ and DCQ. RESULTS: Confirmatory factor analyses
      favored the hypothesized 3-factor model for mothers and fathers for the CQ and
      DCQ. The internal consistencies and convergent validities of the CQ and DCQ were
      adequate. Coparenting conflict and triangulation were significantly higher for
      general child management than diabetes-specific issues. CONCLUSIONS: The CQ and
      DCQ represent two assessments that differentiate couples' cooperation, conflict,
      and triangulation coparenting behaviors for general and diabetes-specific issues,
      and may potentially help inform family-based interventions.

PMID- 21097956
TI  - Use of the Family Interaction Macro-coding System with families of adolescents:
      psychometric properties among pediatric and healthy populations.
AB  - OBJECTIVE: To examine reliability and validity data for the Family Interaction
      Macro-coding System (FIMS) with adolescents with spina bifida (SB), adolescents
      with type 1 diabetes mellitus (T1DM), and healthy adolescents and their families.
      METHODS: Sixty-eight families of children with SB, 58 families of adolescents
      with T1DM, and 68 families in a healthy comparison group completed family
      interaction tasks and self-report questionnaires. Trained coders rated family
      interactions using the FIMS. RESULTS: Acceptable interrater and scale
      reliabilities were obtained for FIMS items and subscales. Observed FIMS parental
      acceptance, parental behavioral control, parental psychological control, family
      cohesion, and family conflict scores demonstrated convergent validity with
      conceptually similar self-report measures. CONCLUSIONS: Preliminary evidence
      supports the use of the FIMS with families of youths with SB and T1DM and healthy
      youths. Future research on overall family functioning may be enhanced by use of
      the FIMS.

PMID- 21097957
TI  - Electro-cortical implicit race bias does not vary with participants' race or sex.
AB  - Earlier research found evidence for electro-cortical race bias towards black
      target faces in white American participants irrespective of the task relevance of
      race. The present study investigated whether an implicit race bias generalizes
      across cultural contexts and racial in- and out-groups. An Australian sample of
      56 Chinese and Caucasian males and females completed four oddball tasks that
      required sex judgements for pictures of male and female Chinese and Caucasian
      posers. The nature of the background (across task) and of the deviant stimuli
      (within task) was fully counterbalanced. Event-related potentials (ERPs) to
      deviant stimuli recorded from three midline sites were quantified in terms of
      mean amplitude for four components: N1, P2, N2 and a late positive complex (LPC;
      350-700 ms). Deviants that differed from the backgrounds in sex or race elicited
      enhanced LPC activity. These differences were not modulated by participant race
      or sex. The current results replicate earlier reports of effects of poser race
      relative to background race on the LPC component of the ERP waveform. In
      addition, they indicate that an implicit race bias occurs regardless of
      participant's or poser's race and is not confined to a particular cultural
      context.

PMID- 21097959
TI  - Who are the defendants in domestic violence protection order cases?
AB  - Domestic violence protective orders (DVPOs) are the nation's most widely used
      intimate partner violence (IPV)-related legal intervention, and there is emerging
      evidence that DVPOs are effective. However, little is known about DVPO
      defendants. We examined a population-based sample of male DVPO defendants. Most
      had previous IPV-related offenses, mental health issues, and alcohol and drug-use
      histories. Court personnel should be aware of the severity of violence plaintiffs
      are likely experiencing, and the potential danger posed by defendants, and ensure
      that expedited and appropriate protection is awarded. Concurrent treatment for
      substance abuse and mental health may enhance the effectiveness of DVPOs.

PMID- 21097958
TI  - The posterior superior temporal sulcus is sensitive to the outcome of human and
      non-human goal-directed actions.
AB  - Prior studies have demonstrated that the posterior superior temporal sulcus
      (pSTS) is involved in analyzing the intentions underlying actions and is
      sensitive to the context within which actions occur. However, it is debated
      whether the pSTS is actually sensitive to goals underlying actions, or whether
      previous studies can be interpreted to suggest that the pSTS is instead involved
      in the allocation of visual attention towards unexpected events. In addition,
      little is known about whether the pSTS is specialized for reasoning about the
      actions of social agents or whether the pSTS is sensitive to the actions of both
      animate and inanimate entities. Here, using functional magnetic resonance
      imaging, we investigated activation in response to passive viewing of successful
      and unsuccessful animate and inanimate goal-directed actions. Activation in the
      right pSTS was stronger in response to failed actions compared to successful
      actions, suggesting that the pSTS plays a role in encoding the goals underlying
      actions. Activation in the pSTS did not differentiate between animate and
      inanimate actions, suggesting that the pSTS is sensitive to the goal-directed
      actions of both animate and inanimate entities.

PMID- 21097960
TI  - Excusable deficiency: staff perceptions of mothering at shelters for abused
      women.
AB  - This study examined how staff members in shelters for abused women perceive the
      women's mothering and the challenges when working with these mothers. Data were
      collected through focus group interviews with 30 workers at Israeli shelters for
      abused women. Findings revealed that workers typically held a "deficit
      perspective" when describing the residents' mothering skills. Most seemed
      committed to the notion of empowerment as a guiding framework for intervention
      with the women and made an effort to facilitate the women's choices and autonomy
      in spite of the obstacles. The study examined workers' perceptions from personal,
      professional, and sociocultural perspectives.

PMID- 21097961
TI  - College women: history of childhood abuse and its relationship to smoking.
AB  - Few studies have examined the influence of childhood abuse on smoking in women.
      The objective of the study was to determine if abuse in childhood is associated
      with increased risk for smoking in women. Two hundred ninety-six women completed
      an anonymous survey on childhood abuse and smoking. Results showed that abuse was
      a better predictor of smoking than status variables. Those experiencing two or
      more abuses before age 17 were three times more likely to be early smokers and
      seven times more likely to be current smokers. Findings highlight abuse in
      childhood as a stressor that increases a woman's risk for smoking.

PMID- 21097963
TI  - Teen magazines as educational texts on dating violence: the $2.99 approach.
AB  - This study analyzed the portrayal of dating violence in teen magazines published
      in the United States. Such an investigation is important because previous
      research indicates that dating violence is a serious problem facing adolescents,
      teen magazines overemphasize the importance of romantic relationships, and teens
      who read this genre frequently or for education/advice are especially susceptible
      to its messages. Results indicated that although teen magazines do frame dating
      violence as a cultural problem, they are much more likely to utilize an
      individual frame that emphasizes the victim. Results were discussed as they apply
      to the responsibilities of professionals working with adolescents.

PMID- 21097962
TI  - Meaningful differences: comparison of adult women who first traded sex as a
      juvenile versus as an adult.
AB  - The authors analyzed experiences, characteristics, and risks of adult women who
      trade sex in Minneapolis, MN (n = 117), and found significant differences between
      women who first traded sex as a juvenile compared with those who first traded sex
      as an adult. Adult starters were 3.44 times more likely to use drugs prior to
      their first sex trade. They were also more likely to hav e children. Juvenile
      starters were more likely to trade sex prior to their first instance of drug use
      and they had worse outcomes in most other domains that were measured. The study
      findings showed that they can be useful in shaping prevention of prostitution and
      methods to be used for its intervention.

PMID- 21097964
TI  - Substance use by soldiers who abuse their spouses.
AB  - Data on 7,424 soldier spouse abuse offenders were analyzed to determine the
      prevalence of substance use during abusive incidents, and to examine differences
      between substance-using and non-substance-using offenders. Results showed that
      25% of all offenders used substances during abusive incidents, with males and non
      Hispanic Whites being more likely to hav e used substances. Substance-using
      offenders were more likely to perpetrate physical spouse abuse and more severe
      spouse abuse. These findings underscore the importance of educating military
      personnel (including commanders) about links between substance use and domestic
      violence, and of coordinating preventive and therapeutic substance abuse and
      violence-related interventions.

PMID- 21097965
TI  - The ethics of research ethics committees.

PMID- 21097966
TI  - Honouring women of the past.

PMID- 21097967
TI  - Images of a 'good nurse' presented by teaching staff.
AB  - Nursing is at the same time a vocation, a profession and a job. By nature,
      nursing is a moral endeavor, and being a 'good nurse' is an issue and an
      aspiration for professionals. The aim of our qualitative research project carried
      out with 18 nurse teachers at a university nursing school in Brazil was to
      identify the ethical image of nursing. In semistructured interviews the
      participants were asked to choose one of several pictures, to justify their
      choice and explain what they meant by an ethical nurse. Five different
      perspectives were revealed: good nurses fulfill their duties correctly; they are
      proactive patient advocates; they are prepared and available to welcome others as
      persons; they are talented, competent, and carry out professional duties
      excellently; and they combine authority with power sharing in patient care. The
      results point to a transition phase from a historical introjection of religious
      values of obedience and service to a new sense of a secular, proactive,
      scientific and professional identity.

PMID- 21097968
TI  - Unresolved pain in children: a relational ethics perspective.
AB  - It is considered the right of children to have their pain managed effectively.
      Yet, despite extensive research findings, policy guidelines and practice standard
      recommendations for the optimal management of paediatric pain, clinical practices
      remain inadequate. Empirical evidence definitively shows that unrelieved pain in
      children has only harmful consequences, with no benefits. Contributing factors
      identified in this undermanaged pain include the significant role of nurses.
      Nursing attitudes and beliefs about children's pain experiences, the
      relationships nurses share with children who are suffering, and knowledge
      deficits in pain management practices are all shown to impact unresolved pain in
      children. In this article, a relational ethics perspective is used to explore the
      need for nurses to engage in authentic relationships with children who are
      experiencing pain, and to use evidence-based practices to manage that pain in
      order for this indefensible suffering of children to end.

PMID- 21097969
TI  - Nurse-focused ethical solutions to problems in organ transplantation.
AB  - Technological developments in recent years have brought about a rapid increase in
      the number and variety of organ transplants, leading to problems in finding
      enough organs to meet the need. Organ transplantation has also become a
      particularly significant issue in medical ethics, especially regarding the
      question of how and from whom organs are procured. Many methods have been tried
      in order to solve these problems and discussed from an ethical perspective. This
      study investigates the Spanish, Belgian and Iranian approaches to solving the
      organ procurement problem. The Spanish model, which is based on persuading
      patients and their relatives, is ethically less problematic and is also an
      improved version of the model applied in Turkey. This study argues that an ideal
      solution can be found without disregarding ethical rules. In particular, nurses
      can contribute by helping to run the system more efficiently. The principal aim
      of this article is to demonstrate the contribution of nurses to solving the
      current organ procurement problem in Turkey and offer some reflections on what
      can be done to improve the efficiency of the system.

PMID- 21097970
TI  - Cultural safety and the socioethical nurse.
AB  - This article explores the social and ethical elements of cultural safety and
      combines them in a model of culturally safe practice that should be of interest
      and relevance for nurses, nurse educators and nurse ethicists in other cultures.
      To achieve this, the article briefly reviews and critiques the main underpinnings
      of the concept from its origins and development in New Zealand, describes its
      sociocultural and sociopolitical elements, and provides an in-depth exploration
      of the key socioethical elements. Finally, a model is presented to illustrate the
      strong connection between the social and ethical components of cultural safety
      that combine to produce culturally safe practice through the activities of a
      'socioethical' nurse.

PMID- 21097971
TI  - Moral distress experienced by psychiatric nurses in Japan.
AB  - This study aimed to: (1) develop and evaluate the Moral Distress Scale for
      Psychiatric nurses (MDS-P); (2) use the MDS-P to examine the moral distress
      experienced by Japanese psychiatric nurses; and (3) explore the correlation
      between moral distress and burnout. A questionnaire on the intensity and
      frequency of moral distress items (the MDS-P: 15 items grouped into three
      factors), a burnout scale (Maslach Burnout Inventory - General Survey) and
      demographic questions were administered to 391 Japanese psychiatric nurses in
      2007-2008. These nurses experienced relatively low levels of moral distress
      despite the fact that they were commonly confronted by morally distressing
      situations. All the circumstances in which the participants experienced moral
      distress were included in the 'low staffing' factor, which reflects the
      characteristics of Japanese psychiatric care. The frequency score of the low
      staffing factor was a significant predictor of burnout.

PMID- 21097972
TI  - Ethical concerns of nursing reviewers: an international survey.
AB  - Editors of scientific literature rely heavily on peer reviewers to evaluate the
      integrity of research conduct and validity of findings in manuscript submissions.
      The purpose of this study was to describe the ethical concerns of reviewers of
      nursing journals. This descriptive cross-sectional study was an anonymous online
      survey. The findings reported here were part of a larger investigation of
      experiences of reviewers. Fifty-two editors of nursing journals (six outside the
      USA) agreed to invite their review panels to participate. A 69-item forced-choice
      and open-ended survey developed by the authors based on the literature was pilot
      tested with 18 reviewers before being entered into SurveyMonkey(TM). A total of
      1675 reviewers responded with useable surveys. Six questions elicited responses
      about ethical issues, such as conflict of interest, protection of human research
      participants, plagiarism, duplicate publication, misrepresentation of data and
      'other'. The reviewers indicated whether they had experienced such a concern and
      notified the editor, and how satisfied they were with the outcome. They provided
      specific examples. Approximately 20% of the reviewers had experienced various
      ethical dilemmas. Although the majority reported their concerns to the editor,
      not all did so, and not all were satisfied with the outcomes. The most commonly
      reported concern perceived was inadequate protection of human participants. The
      least common was plagiarism, but this was most often reported to the editor and
      least often led to a satisfactory outcome. Qualitative responses at the end of
      the survey indicate this lack of satisfaction was most commonly related to
      feedback provided on resolution by the editor. The findings from this study
      suggest several areas that editors should note, including follow up with
      reviewers when they identify ethical concerns about a manuscript.

PMID- 21097973
TI  - The ethical community consultation model as preparation for nursing research: a
      case study.
AB  - This article describes a case study in which community consultation was used to
      assist in the preparation of a research project on viewing self in the mirror
      after mastectomy. Breast cancer survivors, nurses, and other health care
      professionals were consulted using a variety of interactive modalities. Over a
      period of three months, pre-research planning information was obtained from
      participants. A descriptive qualitative design was used to analyze the data. The
      ethical goals of community consultation provided the framework for dialogue and
      the synthesis of information. During this project, the potential benefits of the
      proposed research study were explored. Possible risks to future participants were
      discussed, and recommendations for participant protection suggested. Community
      members provided insight into the legitimacy of the study. Community consultation
      is a tool that researchers may consider when designing studies.

PMID- 21097974
TI  - Evaluation of nursing students' training in medical law.
AB  - There is no co-ordinated focus on liabilities arising from nurses' medical
      interventions in terms of occupational, administrative, civil legal and criminal
      activities. However, the Turkish Criminal Code, the Turkish Medical Ethics Code
      of Practice, and guidelines for patients' rights offer some framework for the
      relevant ethical principles and responsibilities of nurses. The aim of this study
      was to investigate the evaluation of nursing students' training in their legal
      liabilities. The sample consisted of 309 students who were taking a course
      entitled 'Nurses' legal liabilities under Turkish criminal and civil law arising
      from medical interventions'. Data were obtained by means of self-administered
      questionnaires and McNemar's test was used to evaluate the answers. In
      conclusion, after their training, a great majority of the students demonstrated
      an improvement in terms of their percentage of correct answers relating to
      malpractice. This does not, however, mean that they will not face malpractice
      charges after graduating, but their increased awareness of the issue may
      encourage them to make more effort to reduce the risk of mistakes. It is
      recommended that nursing faculty carry out studies into medical malpractice, that
      they focus more on this subject in nursing education, and that all nursing
      schools review their curricula from the point of view of malpractice.

PMID- 21097975
TI  - Ethics in independent nurse consulting: strategies for avoiding ethical
      quicksand.
AB  - Changes in health care have created a variety of new roles and opportunities for
      nurses in advanced practice. One of these changes is the increasing number of
      advanced practice nurses carrying out independent consultation. Differences in
      goals between business and health care may create ethical dilemmas for nurse
      consultants. The purpose of this article is to describe possible ethical pitfalls
      that nurse consultants may encounter and strategies to prevent or solve these
      dilemmas. Three themes related to nursing codes of ethics will be discussed: the
      duty to uphold human rights, the duty to fulfill commitments, and the duty to
      practice the profession competently.

PMID- 21097976
TI  - Nurses' ethical reflections on caring for people with malodorous exuding ulcers.
AB  - The aim of this study was to illuminate nurses' reflections on obstacles to and
      possibilities for providing care as desired by people with malodorous exuding
      ulcers. Six nurses who took part in a previous study were interviewed. The
      participants were shown an illustration with findings from a study that
      elucidated the meaning of living with malodorous exuding ulcers. They were asked
      to reflect on the obstacles to and possibilities of providing the care desired by
      the patients. Twelve audio-recorded transcribed interviews were analysed using
      qualitative content analysis. Our interpretations of participants' reflections on
      the obstacles and possibilities while caring for such patients revealed one
      theme: striving to 'do good' and 'be good'. The obstacles were formulated as
      subthemes: experiencing clinical competence constraints, experiencing
      organizational constraints, experiencing ineffective communication, fearing
      failure, and experiencing powerlessness. The possibilities were formulated by the
      subthemes: spreading knowledge about ulcer treatments, considering wholeness, and
      creating clear channels of communication. A multiprofessional team could overcome
      the identified obstacles and provide structure, competencies, commitment and
      support to 'do good' for patients and 'be good' nurses.

PMID- 21097977
TI  - Informed consent practices of Chinese nurse researchers.

PMID- 21097980
TI  - Thyroid glands from pigs with cystic fibrosis, old issues new ways.

PMID- 21097981
TI  - Parallel anxiolytic-like effects and upregulation of neuronal nicotinic
      acetylcholine receptors following chronic nicotine and varenicline.
AB  - INTRODUCTION: Clinical and preclinical studies suggest that regulation of
      nicotinic acetylcholine receptors (nAChR) maybe involved in the etiology of
      withdrawal symptoms. METHODS: We evaluated heteromeric nAChR regulation via
      [3H]epibatidine binding following cessation of chronic nicotine or varenicline
      treatment. Animals were concurrently tested in the marble-burying test to
      evaluate treatment-related effects. RESULTS: We found that both nicotine (18
      mg/kg/day, free base) and varenicline (1.8 mg/kg/day) chronically administered
      for 14 days upregulated nAChRs significantly in the cortex, hippocampus,
      striatum, and thalamus. The duration of upregulation (up to 72 hr) was both drug
      and region specific. In addition to nAChR upregulation, chronic administration of
      both nicotine and varenicline had anxiolytic-like effects in the marble-burying
      test. This effect was maintained for 48 hr following cessation of varenicline but
      was absent 24 hr following cessation from nicotine. Additionally, marble-burying
      behavior positively correlated to the regulation of cortical nAChRs following
      cessation of either treatment. CONCLUSIONS: Varenicline has been shown to be an
      efficacious smoking cessation aid, with a proposed mechanism of action that
      includes modulation of dopamine release in reward areas of the brain. Our studies
      show that varenicline elicits both anxiolytic effects in the marble-burying test
      as well as region- and time-specific receptor upregulation. These findings
      suggest receptor upregulation as a mechanism for its efficacy as a smoking
      cessation therapy.

PMID- 21097982
TI  - Antenatal magnesium sulphate.

PMID- 21097985
TI  - Imaging the dead.

PMID- 21097987
TI  - Experts demand major revisions of German gene diagnostics law.

PMID- 21097988
TI  - Is cardiotoxicity being adequately assessed in current trials of cytotoxic and
      targeted agents in breast cancer?
AB  - The cardiotoxicity of anthracyclines, trastuzumab and other agents is of special
      importance to adjuvant breast cancer patients whose life expectancy is restored
      to normal but who may be left with cardiac abnormalities that can present years
      later. We systematically reviewed the design of current trials (including
      adjuvant studies) on the clinicaltrials.gov Web site. Surprisingly few specify
      primary or secondary cardiac end points. Although cardiac ultrasound
      (echocardiography) and multiple uptake gated acquisition scintigraphy remain the
      most frequent techniques for estimating left ventricular ejection fraction, there
      is no consistency in the degree of reduction from baseline or absolute value
      taken as indicating cardiotoxicity. The details given do not suggest that
      diastolic function (which may give earlier warning of problems) is a focus of
      interest. There is growing interest in troponin as a marker of myocyte death and
      brain natriuretic peptide as a marker of myocardial stress and possible heart
      failure (though their clinical usefulness has still to be adequately defined).
      The duration of follow-up in many adjuvant studies may not be sufficient to
      determine the risk of late cardiac events. The findings indicate a need to study
      and standardize cardiac toxicity assessments in oncology trials.

PMID- 21097990
TI  - A rotating bluff-body disc for reduced variability in wind tunnel aerosol
      studies.
AB  - A rotating bluff-body disc (RBD) was developed to reduce spatiotemporal
      variability associated with sampling supermicron aerosol in low-velocity wind
      tunnels. The RBD is designed to rotate eight personal aerosol samplers around a
      circular path in a forward-facing plane aligned with the wind tunnel cross
      section. Rotation of the RBD allows each sampler to traverse an identical path
      about the wind tunnel cross section, which reduces the effects of spatial
      heterogeneity associated with dispersing supermicron aerosol in low-velocity wind
      tunnels. Samplers are positioned on the face of the RBD via sampling ports, which
      connect to an air manifold on the back of the disc. Flow through each sampler was
      controlled with a critical orifice or needle valve, allowing air to be drawn
      through the manifold with a single pump. A metal tube, attached to this manifold,
      serves as both the axis of rotation and the flow conduction path (between the
      samplers and the vacuum source). Validation of the RBD was performed with
      isokinetic samplers and 37-mm cassettes. For facing-the-wind tests, the rotation
      of the RBD significantly decreased intra-sampler variability when challenged with
      particle diameters from 1 to 100 MUm. The RBD was then employed to determine the
      aspiration efficiency of Institute of Occupational Medicine (IOM) personal
      samplers under a facing-the-wind condition. Operation of IOM samplers on the RBD
      reduced the between-sampler variability for all particle sizes tested.

PMID- 21097989
TI  - Insight in psychosis: relationship with neurocognition, social cognition and
      clinical symptoms depends on phase of illness.
AB  - Reduced insight has been reported in a majority of patients with a psychotic
      disorder. Most studies have focused on associations with neurocognition,
      neglecting relations with social cognition. Two hundred seventy patients with
      nonaffective psychosis participated in this study, which was part of the GROUP
      (Genetic Risk and OUtcome of Psychosis)-project. Linear regression analyses were
      performed to investigate the predictive value of composite measures of
      neurocognition, social cognition, and clinical symptoms. The moderating effect of
      phase of illness was also investigated. Insight was measured with a composite
      measure, based on the insight item on the Positive And Negative Syndrome Scale
      (PANSS) and the Birchwood Insight Scale (BIS). Insight on the BIS and the PANSS
      correlated significantly (r = .406). All independent variables correlated with
      the insight composite measure. The additional effect of social cognition and
      clinical symptoms were both significant. Phase of illness was a moderating
      variable: In patients with recent-onset psychosis (ROP), none of the independent
      variables explained variance. In patients with multiple episode or chronic
      psychosis, both social cognition and clinical symptoms had additional effects and
      explained insight, along with neurocognition, together explaining 20% of the
      variance. These findings indicate that multiple factors are associated with
      insight in psychosis. Specifically, associations of insight with social cognitive
      and clinical symptom measures were observed, over and above a contribution of
      neurocognition. This supports theories that imply a role for deficient emotion
      recognition and mentalizing in reduced insight. Further studies need to
      investigate insight in ROP into more detail.

PMID- 21097991
TI  - Maxillary and mandibular mesiodistal tooth sizes among different malocclusions in
      a sample of the Turkish population.
AB  - The purpose of this study was to establish normative data for mesiodistal tooth
      crown dimensions with respect to malocclusions and gender differences in Turkish
      sample. The subjects were randomly selected and assigned to three malocclusion
      groups according to Angle's classification. Each group consisted of 100
      individuals between the ages of 13 and 18 years with the following distribution:
      Class I, 42 males and 58 females; Class II, 52 males and 48 females; and Class
      III, 51 males and 49 females. An electronic digital calliper was used to measure
      the mesiodistal tooth width from the right second permanent molar to the left
      second permanent molar on both upper and lower study casts. For statistical
      evaluation, one- and two-way analyses of variance and post hoc Tukey's honestly
      significant difference (HSD) tests were performed. There were statistically
      significant differences for the maxillary canine (P < 0.001), first premolar (P <
      0.05), second molar (P < 0.05), and mandibular canine (P < 0.01) for males, and
      for all maxillary teeth and the mandibular central (P < 0.05), canine (P <
      0.001), and first premolar (P < 0.05) teeth in females among the malocclusion
      groups. When Angle's classification was evaluated, significant differences were
      determined, except for the first and second mandibular molars. All mesiodistal
      widths were also found to be statistically different according to gender
      dimorphism. A significant relationship was found between mesiodistal tooth size,
      Angle's classification, and gender. Therefore, tooth dimensions may play a
      crucial role in treatment planning and in achieving satisfactory interdigitation
      of the upper and lower dentition following the completion of orthodontic
      treatment.

PMID- 21097992
TI  - A mixed longitudinal anthropometric study of craniofacial growth of Colombian
      mestizos 6-17 years of age.
AB  - The purpose of this study was to evaluate the craniofacial growth of Colombian
      mestizos. Four age cohorts, including a total of 458 children and adolescents
      (262 males and 216 females), were included in this mixed-longitudinal study. The
      cohorts were first measured at ages 6, 9, 12, and 15 and every year thereafter
      for 3 years. Eight anthropometric measurements were taken, including three
      cranial (head perimeter, head width, and head length), two craniofacial
      (maxillary and mandibular length), and three facial (face height, bizygomatic
      width, and bigonial width). Multilevel analyses showed that all dimensions
      increased between 6 and 17 years of age. The cranium grew less than the
      craniofacial, which in turn grew less than the facial dimensions. In addition,
      vertical dimensions showed more growth than antero-posterior dimensions, which in
      turn grew more than transverse dimensions. None of the measurement showed
      statistically significant growth differences between subjects with normal
      occlusion and Class I or Class II malocclusions. Males were generally larger than
      females and showed greater growth rates. Except for facial width, whose yearly
      velocities decreased regularly with age, an adolescent growth spurt was evident
      for most of the male measurements. Yearly velocities for females followed a
      simpler decelerating pattern. The results provide reference data for Colombian
      mestizos, for whom normative data of other ethnic groups are not applicable.
      While occlusion had little or no effect, there were gender differences, as well
      as important growth differences between cranial and facial measurements.

PMID- 21097993
TI  - Stimulus repetition probability does not affect repetition suppression in macaque
      inferior temporal cortex.
AB  - Recent human functional magnetic resonance imaging studies (Summerfield C,
      Trittschuh EH, Monti JM, Mesulam MM, Egner T. 2008. Neural repetition suppression
      reflects fulfilled perceptual expectations. Nat Neurosci. 11:1004-1006.) showed
      that adaptation or repetition suppression is affected by contextual factors
      related to perceptual expectations, suggesting that adaptation results from a
      fulfillment of perceptual expectation or a reduction in prediction error. This
      view contrasts with the bottom-up fatigue or sharpening mechanisms of adaptation
      proposed in single-cell studies. We examined whether stimulus repetition
      probability affects adaptation of spiking activity and local field potentials
      (LFPs) in macaque inferior temporal (IT) cortex, using a protocol similar to that
      of Summerfield et al. Monkeys were exposed to 2 randomly interleaved trials, each
      consisting of either 2 identical (rep trial) or 2 different stimuli (alt trial).
      Trials were presented in repetition (rep) blocks consisting of 75% of rep trials
      and 25% of alt trials or in alternation (alt) blocks having opposite repetition
      probabilities. For both spiking and LFP activities, the stimulus-selective
      adaptation did not differ significantly between rep and alt blocks. The number of
      preceding rep or alt trials and the trial position within a block did not affect
      adaptation. This absence of any effect of stimulus repetition probability on
      adaptation suggests that adaptation in IT is not caused by contextual factors
      related to perceptual expectation.

PMID- 21097994
TI  - Renal growth retardation following angiotensin II type 1 (AT1) receptor
      antagonism is associated with increased AT2 receptor protein in fetal sheep.
AB  - The actions of angiotensin II on type 1 (AT1) and type 2 (AT2) receptor subtypes
      are important for normal kidney development before birth. This study investigated
      the effect of AT1 receptor antagonism on renal growth and growth regulators in
      fetal sheep during late gestation. From 125 days of gestation (term 145+/-2
      days), chronically catheterised sheep fetuses were infused intravenously for 5
      days with either an AT1-specific receptor antagonist (GR138950, 2-4 mg/kg per
      day, n=5) or saline (0.9% NaCl, n=5). Blockade of the AT1 receptor decreased
      arterial blood oxygenation and pH and increased blood pCO2, haemoglobin and
      lactate, and plasma cortisol and IGF-II. Blood glucose and plasma thyroid
      hormones and IGF-I were unchanged between the treatment groups. On the 5th day of
      infusion, the kidneys of the GR-treated fetuses were lighter than those of the
      control fetuses, both in absolute and relative terms, and were smaller in
      transverse cross-sectional width and cortical thickness. In the GR-infused
      fetuses, renal AT2 receptor protein concentration and glomerular density were
      significantly greater than in the saline-infused fetuses. Blockade of the AT1
      receptor had no effect on relative cortical thickness, fractional or mean
      glomerular volumes, or renal protein levels of the AT1 receptor, IGF type 1
      receptor, insulin receptor or protein kinase C zeta. Therefore, in the ovine
      fetus, AT1 receptor antagonism causes increased renal protein expression of the
      AT2 receptor subtype, which, combined with inhibition of AT1 receptor activity,
      may be partly responsible for growth retardation of the developing kidney.

PMID- 21097995
TI  - Chemical allergy: translating biology into hazard characterization.
AB  - The induction by chemicals of allergic sensitization and allergic disease is an
      important and challenging branch of toxicology. Skin sensitization resulting in
      allergic contact dermatitis represents the most common manifestation of
      immunotoxicity in humans, and many hundreds of chemicals have been implicated as
      skin sensitizers. There are far fewer chemicals that have been shown to cause
      sensitization of the respiratory tract and asthma, but the issue is no less
      important because hazard identification remains a significant challenge, and
      occupational asthma can be fatal. In all areas of chemical allergy, there have
      been, and remain still, intriguing challenges where progress has required a close
      and productive alignment between immunology, toxicology, and clinical medicine.
      What the authors have sought to do here is to exemplify, within the framework of
      chemical allergy, how an investment in fundamental research and an improved
      understanding of relevant biological and biochemical mechanisms can pay important
      dividends in driving new innovations in hazard identification, hazard
      characterization, and risk assessment. Here we will consider in turn three
      specific areas of research in chemical allergy: (1) the role of epidermal
      Langerhans cells in the development of skin sensitization, (2) T lymphocytes and
      skin sensitization, and (3) sensitization of the respiratory tract. In each area,
      the aim is to identify what has been achieved and how that progress has impacted
      on the development of new approaches to toxicological evaluation. Success has
      been patchy, and there is still much to be achieved, but the journey has been
      fascinating and there have been some very important developments. The conclusion
      drawn is that continued investment in research, if coupled with an appetite for
      translating the fruits of that research into imaginative new tools for
      toxicology, should continue to better equip us for tackling the important
      challenges that remain to be addressed.

PMID- 21097996
TI  - Acute imidazenil treatment after the onset of DFP-induced seizure is more
      effective and longer lasting than midazolam at preventing seizure activity and
      brain neuropathology.
AB  - Diazepam (DZ), the preferred anticonvulsant benzodiazepine (BZ) for the treatment
      of organophosphate (OP) nerve agent-induced seizures and neuronal damage, has
      been associated with unwanted effects such as sedation, amnesia,
      cardiorespiratory depression, anticonvulsant tolerance, and dependence liability.
      In a search for safer and more effective anticonvulsant BZs against OP-induced
      seizure and neuronal damage, we have previously shown that imidazenil (IMD), a
      low-intrinsic efficacy positive allosteric modulator of gamma-aminobutyric acid
      (GABA) action at alpha1-containing GABA(A) receptors, which has high intrinsic
      efficacy at alpha2-, alpha3-, and alpha5-containing GABA(A) receptors, is more
      potent and longer lasting than DZ pretreatment at protecting rats from
      diisopropyl fluorophosphate (DFP)-induced electrocorticographic (ECoG) seizures
      and neuronal damage. The effects of IMD were observed at doses that are devoid of
      sedative, amnestic, and anticonvulsant tolerance actions. In the present study,
      we compared the anticonvulsant and neuroprotective effects of a combination of
      atropine (2 mg/kg, ip) and pyridine-2-aldoxime methochloride (2-PAM, 20 mg/kg,
      ip) with IMD (0.5 mg/kg, ip) or midazolam (MDZ, 0.5-2 mg/kg, ip) administered
      after the onset of DFP (1.5 mg/kg, sc)-induced seizure activity. The severity of
      DFP-induced ECoG seizures was assessed by continuous radio telemetry recordings
      in unrestrained and freely moving rats. Furthermore, the extent of neuronal
      damage was evaluated using a neuron-specific nuclear protein immunolabeling and
      fluoro-jade B staining procedure. We report here that IMD is more efficacious and
      longer lasting than sedating doses of MDZ in protecting rats from DFP-induced
      ECoG seizures and neuronal damage.

PMID- 21097997
TI  - Application of transcriptional benchmark dose values in quantitative cancer and
      noncancer risk assessment.
AB  - The traditional approach for estimating noncancer and cancer reference values in
      quantitative chemical risk assessment is time and resource intensive. The extent
      and nature of the studies required under the traditional approach has limited the
      number of chemicals with published risk assessments. In this study, female mice
      were exposed for 13 weeks to multiple concentrations of five chemicals that were
      positive in a 2-year cancer bioassay. Traditional histological and organ weight
      changes were evaluated, and gene expression microarray analysis was performed on
      the target tissues. The histological, organ weight changes, and the original
      tumor incidences in the original cancer bioassay were analyzed using standard
      benchmark dose (BMD) methods to identify noncancer and cancer points of
      departure, respectively. The dose-related changes in gene expression were also
      analyzed using a BMD approach and the responses grouped based on cellular
      biological processes. A comparison of the transcriptional BMD values with those
      for the traditional noncancer and cancer apical endpoints showed a high degree of
      correlation for specific cellular biological processes. For chemicals with human
      exposure data, the transcriptional BMD values were also used to calculate a
      margin of exposure. The margins of exposure ranged from 1900 to 54,000. Both the
      correlation between the BMD values for the transcriptional and apical endpoints
      and the margin of exposure analysis suggest that transcriptional BMD values may
      be used as potential points of departure for noncancer and cancer risk
      assessment.

PMID- 21097998
TI  - Evolution of elongation factor G and the origins of mitochondrial and chloroplast
      forms.
AB  - Protein synthesis elongation factor G (EF-G) is an essential protein with central
      roles in both the elongation and ribosome recycling phases of protein synthesis.
      Although EF-G evolution is predicted to be conservative, recent reports suggest
      otherwise. We have characterized EF-G in terms of its molecular phylogeny,
      genomic context, and patterns of amino acid substitution. We find that most
      bacteria carry a single "canonical" EF-G, which is phylogenetically conservative
      and encoded in an str operon. However, we also find a number of EF-G paralogs.
      These include a pair of EF-Gs that are mostly found together and in an eclectic
      subset of bacteria, specifically delta-proteobacteria, spirochaetes, and
      planctomycetes (the "spd" bacteria). These spdEFGs have also given rise to the
      mitochondrial factors mtEFG1 and mtEFG2, which probably arrived in eukaryotes
      before the eukaryotic last common ancestor. Meanwhile, chloroplasts apparently
      use an alpha-proteobacterial-derived EF-G rather than the expected cyanobacterial
      form. The long-term comaintenance of the spd/mtEFGs may be related to their
      subfunctionalization for translocation and ribosome recycling. Consistent with
      this, patterns of sequence conservation and site-specific evolutionary rate
      shifts suggest that the faster evolving spd/mtEFG2 has lost translocation
      function, but surprisingly, the protein also shows little conservation of sites
      related to recycling activity. On the other hand, spd/mtEFG1, although more
      slowly evolving, shows signs of substantial remodeling. This is particularly
      extensive in the GTPase domain, including a highly conserved three amino acid
      insertion in switch I. We suggest that subfunctionalization of the spd/mtEFGs is
      not a simple case of specialization for subsets of original activities. Rather,
      the duplication allows the release of one paralog from the selective constraints
      imposed by dual functionality, thus allowing it to become more highly
      specialized. Thus, the potential for fine tuning afforded by subfunctionalization
      may explain the maintenance of EF-G paralogs.

PMID- 21097999
TI  - CpG Islands as a putative source for animal miRNAs: evolutionary and functional
      implications.
AB  - MicroRNAs (miRs) are considered major contributors to the evolution of animal
      morphological complexity. Multiple bursts of novel miR families were documented
      throughout animal evolution, yet, their evolutionary origins are not understood.
      Here, we discuss two alternative genomic sources for novel miR families, namely,
      transposable elements, which were previously described, and a newly proposed
      origin: CpG islands. We show that these two origins are evolutionarily distinct
      and that they correspond to marked differences in several functional and genomic
      characteristics. Together, our results shed light on the intriguing origin of one
      of the major constituents of regulatory networks in animals, miRs.

PMID- 21098000
TI  - Origin of Nogo-A by domain shuffling in an early jawed vertebrate.
AB  - Unlike mammals, fish are able to regenerate axons in their central nervous
      system. This difference has been partly attributed to the loss/acquisition of
      inhibitory proteins during evolution. Nogo-A--the longest isoform of the
      reticulon4 (rtn4) gene product--is commonly found in mammalian myelin where it
      acts as a potent inhibitor of axonal regeneration. Interestingly, fish RTN4
      isoforms were previously reported to lack the most inhibitory Nogo-A-specific
      region (NSR). Nevertheless, fish axons collapse on contact with mammalian NSR,
      suggesting that fish possess a functional Nogo-A receptor but not its ligand. To
      reconcile these findings, we revisited the early evolution of rtn4. Mining of
      current genome databases established the unequivocal presence of NSR-coding
      sequences in fish rtn4 paralogues. Further comparative analyses indicate that the
      common ancestor of fish and tetrapods had an NSR-coding rtn4 gene, which
      underwent duplication and divergent evolution in bony fish. Our genomic survey
      also revealed that the cephalochordate Branchiostoma floridae contains a single
      rtn gene lacking the NSR. Hence, Nogo-A most probably arose independently in the
      rtn4 gene of a gnathostome ancestor before the split of the fish and tetrapod
      lineages. Close examination of the NSR uncovered clusters of structural and
      sequential similarities with neurocan (NCAN), an inhibitory proteoglycan of the
      glial scar. Notably, the shared presence of transposable elements in ncan and
      rtn4 genes suggests that Nogo-A originated via insertion of an ncan-like sequence
      into the rtn4 gene of an early jawed vertebrate with myelinated axons.

PMID- 21098001
TI  - Morphological and functional changes in guinea-pig neurons projecting to the
      ileal mucosa at early stages after inflammatory damage.
AB  - In the present study the relationship between tissue damage and changed electro
      physiological properties of Dogiel type II myenteric neurons within the first 24
      hours after induction of inflammation with trinitrobenzene sulfonate (TNBS) in
      the guinea-pig ileum was investigated. Treatment with TNBS causes damage to the
      mucosa, inflammatory responses in the mucosa and enteric ganglia and changes in
      myenteric neuron properties. Thus we hypothesise that the physiological changes
      in the myenteric neurons could be due to damage to their mucosal processes or
      inflammation in the vicinity of cell bodies or the processes. We found an
      association between hyperexcitability of myenteric Dogiel type II neurons and
      damage to the mucosa and its innervation at 3 and 24 h, times when there was also
      an inflammatory reaction. The lack of hyperexcitability in neurons from control
      tissues in which axons projecting to the mucosa were severed suggests that
      inflammation may be an important contributing factor to the neuronal
      hyperexcitability at the acute stage of inflammation. Despite mucosal repair and
      re-innervation of the mucosa before 7 days after induction of inflammation,
      neuronal hyperexcitability persists. Although the mechanisms underlying neuronal
      hyperexcitability at the acute stage of inflammation might be different from
      those underlying long-term changes in the absence of active inflammation in the
      ganglia, the persistent changes in neuronal excitability may contribute to post
      inflammatory gut dysfunctions.

PMID- 21098002
TI  - Formation of the non-functional and functional pools of granule cells in the
      dentate gyrus: role of neurogenesis, LTP and LTD.
AB  - Some aspects of the function of the dentate gyrus (DG) and CA3 regions of the
      hippocampus are beginning to be understood, notably the way that grid cell inputs
      from the medial entorhinal cortex (MEC) are processed to form place cells in the
      dentate/CA3. However, one aspect of DG function remains very puzzling: more than
      95% of the cells do not fire in any environment. Here, I propose a possible
      explanation for these non-functional cells. Because of the competition mediated
      by feedback inhibition, only the most excited DG cells fire. Cells that do not
      spike nevertheless receive excitatory input from the grid cells of the MEC (these
      cells fire nearly continuously because they represent a property (space) that is
      always being processed). Experiments suggest that synapses on such cells will
      undergo long-term depression (LTD). Cells that have their synapses weakened in
      this way are less likely to be winners in subsequent competitions. There may thus
      be a downward spiral in which losers eventually have no chance of winning and
      thus become non-functional. On the other hand, cells that fire get stronger
      synapses, making them more likely to be subsequent winners. Because the long-term
      potentiation (LTP) in these cells balances ongoing LTD, these cells will be
      relatively stable members of the functional pool. Although these pools are
      relatively stable, there will nevertheless be some chance that LTD converts a
      functional cell to a non-functional one; in contrast, the probability of a
      reverse transition is near zero. Thus, without additional processes, there would
      be a slow reduction in the size of the functional pool. I suggest that the
      ongoing generation of new cells by neurogenesis may be a solution to this
      problem. These cells are highly excitable and may thus win the competition to
      fire. In this way, the functional pool will be replenished. To test this and
      other theories about the DG requires an understanding of the role of the DG in
      memory. Recent experimental and theoretical work is providing a better
      understanding of the unique memory functions of the DG/CA3 unit. This will
      provide a behavioural framework for testing the ideas proposed here.

PMID- 21098003
TI  - Plasma pH does not influence the cerebral metabolic ratio during maximal whole
      body exercise.
AB  - Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose+1/2
      lactate) and metabolic acidosis appears to promote cerebral lactate uptake.
      However, the influence of pH on cerebral lactate uptake and, in turn, on the
      cerebral metabolic ratio during exercise is not known. Sodium bicarbonate
      (Bicarb, 1 M; 350-500 ml) or an equal volume of normal saline (Sal) was infused
      intravenously at a constant rate during a '2000 m' maximal ergometer row in six
      male oarsmen (23+/-2 years; mean+/-S.D.). During the Sal trial, pH decreased from
      7.41+/-0.01 at rest to 7.02+/-0.02 but only to 7.36+/-0.02 (P <0.05) during the
      Bicarb trial. Arterial lactate increased to 21.4+/-0.8 and 32.7+/-2.3 mM during
      the Sal and Bicarb trials, respectively (P <0.05). Also, the arterial-jugular
      venous lactate difference increased from-0.03+/-0.01 mM at rest to 3.2+/-0.9 mM
      (P <0.05) and 3.4+/-1.4 mM (P <0.05) following the Sal and Bicarb trials,
      respectively. Accordingly, the cerebral metabolic ratio decreased equally during
      the Sal and Bicarb trials: from 5.8+/-0.6 at rest to 1.7+/-0.1 and 1.8+/-0.2,
      respectively. The enlarged blood-buffering capacity after infusion of Bicarb
      eliminated metabolic acidosis during maximal exercise but that did not affect the
      cerebral lactate uptake and, therefore, the decrease in the cerebral metabolic
      ratio.

PMID- 21098004
TI  - Human control of an inverted pendulum: is continuous control necessary? Is
      intermittent control effective? Is intermittent control physiological?
AB  - Human motor control is often explained in terms of engineering 'servo' theory.
      Recently, continuous, optimal control using internal models has emerged as a
      leading paradigm for voluntary movement. However, these engineering paradigms are
      designed for high band-width, inflexible, consistent systems whereas human
      control is low bandwidth and flexible using noisy sensors and actuators. By
      contrast, engineering intermittent control was designed for bandwidth-limited
      applications. Our general interest is whether intermittent rather than continuous
      control is generic to human motor control. Currently, it would be assumed that
      continuous control is the superior and physiologically natural choice for
      controlling unstable loads, for example as required for maintaining human
      balance. Using visuo-manual tracking of an unstable load, we show that control
      using gentle, intermittent taps is entirely natural and effective. The gentle
      tapping method resulted in slightly superior position control and velocity
      minimisation, a reduced feedback time delay, greater robustness to changing
      actuator gain and equal or greater linearity with respect to the external
      disturbance. Control was possible with a median contact rate of 0.8+/-0.3 s(-1).
      However, when optimising position or velocity regulation, a modal contact rate of
      2 s(-1) was observed. This modal rate was consistent with insignificant
      disturbance-joystick coherence beyond 1-2 Hz in both tapping and continuous
      contact methods. For this load, these results demonstrate a motor control process
      of serial ballistic trajectories limited to an optimum rate of 2 s(-1).
      Consistent with theoretical reasoning, our results suggest that intermittent open
      loop action is a natural consequence of human physiology.

PMID- 21098005
TI  - Phosphodiesterase 4 inhibition attenuates atrial natriuretic peptide-induced
      vascular hyperpermeability and loss of plasma volume.
AB  - Inhibition of phosphodiesterase 4 (PDE4) to increase endothelial cAMP and
      stabilize the endothelial barrier attenuates acute inflammatory increases in
      vascular permeability.We extended this approach to attenuate physiological
      increases in vascular permeability in response to atrial natriuretic peptide
      (ANP), which acts with the kidney to regulate plasma volume. We measured blood-to
      tissue albumin clearance and changes in plasma volume in isoflurane-anaesthetized
      mice (C57BL/6J) pre-treated with rolipram (8 mg kg(-1) I.P., 30 min). Rolipram
      significantly reduced albumin permeability, measured using a dual-label
      fluorescence method, in skin and skeletal muscle compared with ANP alone (500 ng
      kg(-1) min(-1)). Skin and muscle tissue accounted for 70% of the reduction in
      whole body albumin clearance taking into account albumin clearance in
      gastrointestinal (GI) tissue, heart and kidney. The action of ANP and rolipram to
      modify albumin clearances in duodenum and jejunum could be accounted for by local
      increases in vascular perfusion to increase surface area for exchange. ANP
      increased haematocrit from 40.6% to 46.8%, corresponding to an average loss of
      22% plasma fluid volume (227 MUl), and this was almost completely reversed with
      rolipram. Renal water excretion accounted for less than 30% of plasma fluid loss
      indicating that reduced albumin permeability and reduced filtration into
      vasodilated GI tissue were the predominant actions of PDE4 inhibition. Similar
      fluid retention was measured in mice with endothelial-restricted deletion of the
      guanylyl cyclase-A receptor for ANP. Stabilizing the endothelial barrier to
      offset ANP-induced increases in vascular permeability may be part of a strategy
      to maintain plasma volume.

PMID- 21098006
TI  - Overestimation of force during matching of externally generated forces.
AB  - If a weight is applied to a finger and the subject asked to produce the same
      force, the subject generates a force larger than the weight. That is, subjects
      overestimate the force applied by an external target when matching it. Details of
      this force overestimation are not well understood. We show that subjects
      overestimate small target weights, but not larger ones. Furthermore we show for
      the first time that the force overestimation consists of two components. The
      first component is a constant. The second component depends on the precise
      magnitude of the weight and is only present when subjects hold the target weight
      against gravity. We suggest that the two components are generated in different
      phases of the force-matching task, are due to different processes, and must have
      an influence on all proprioceptive judgements of force.

PMID- 21098007
TI  - Plasticity in human motor cortex is in part genetically determined.
AB  - Brain plasticity refers to changes in the organization of the brain as a result
      of different environmental stimuli. The aim of this study was to assess the
      genetic variation of brain plasticity, by comparing intrapair differences between
      monozygotic (MZ) and dizygotic (DZ) twins. Plasticity was examined by a paired
      associative stimulation (PAS) in 32 healthy female twins (9 MZ and 7 DZ pairs,
      aged 22.6+/-2.7 and 23.8+/-3.6 years, respectively). Stimulation consisted of low
      frequency repetitive application of single afferent electric stimuli, delivered
      to the right median nerve, paired with a single pulse transcranial magnetic
      stimulation (TMS) for activation of the abductor pollicis brevis muscle (APB).
      Corticospinal excitability was monitored for 30 min following the intervention.
      PAS induced an increase in the amplitudes of the motor evoked potentials (MEP) in
      the resting APB, compared to baseline. Intrapair differences, after baseline
      normalization, in the MEP amplitudes measured at 25-30 min post-intervention,
      were almost double for DZ (1.25) in comparison to MZ (0.64) twins (P =0.036). The
      heritability estimate for brain plasticity was found to be 0.68. This finding
      implicates that genetic factors may contribute significantly to interindividual
      variability in plasticity paradigms. Genetic factors may be important in adaptive
      brain reorganization involved in motor learning and rehabilitation from brain
      injury.

PMID- 21098009
TI  - Morphological and electrical properties of oligodendrocytes in the white matter
      of the corpus callosum and cerebellum.
AB  - In the central nervous system, electrical signals passing along nerve cells are
      speeded by cells called oligodendrocytes, which wrap the nerve cells with a fatty
      layer called myelin. This layer is important for rapid information processing,
      and is often lost in disease, causing mental or physical impairment in multiple
      sclerosis, stroke, cerebral palsy and spinal cord injury. The myelin speeds the
      information flow in two ways, by decreasing the capacitance of the nerve cell and
      by increasing its membrane resistance, but little is known about the latter
      aspect of myelin function. By recording electrically from oligodendrocytes and
      imaging their morphology we characterised the geometry and, for the first time,
      the resistance of myelin in the brain. This revealed differences between the
      properties of oligodendrocytes in two brain areas and established that the
      resistance of myelin is sufficiently high to prevent significant slowing of the
      nerve electrical signal by current leakage through the myelin.

PMID- 21098010
TI  - Cryoglobulinaemia and rapidly deteriorating renal function in chronic lymphocytic
      leukaemia.
AB  - Cryoglobulinaemia is a rare condition characterized by serum immunoglobulins or
      immunocomplexes which precipitate at temperatures below 37  degrees C and
      redissolve on warming. Cryoglobulinaemic vasculitis develops in ~ 15% of patients
      positive for cryoglobulin serology and is often associated with an underlying
      infectious, autoimmune or lymphoproliferative disease. We describe a case of
      cryoglobulinaemic vasculitis, which manifested as purpura and rapidly
      deteriorating renal function in a patient with chronic lymphocytic leukaemia and
      coexistent parvovirus infection. This case illustrates the complex
      pathophysiology of cryoglobulinaemic renal injury, and suggests that infection
      may serve as a trigger in the presence of other pathophysiological factors.

PMID- 21098008
TI  - Mechanisms of closed-state inactivation in voltage-gated ion channels.
AB  - Inactivation of voltage-gated ion channels is an intrinsic auto-regulatory
      process necessary to govern the occurrence and shape of action potentials and
      establish firing patterns in excitable tissues. Inactivation may occur from the
      open state (open-state inactivation, OSI) at strongly depolarized membrane
      potentials, or from pre-open closed states (closed-state inactivation, CSI) at
      hyperpolarized and modestly depolarized membrane potentials. Voltage-gated Na(+),
      K(+), Ca(2+) and non-selective cationic channels utilize both OSI and CSI.
      Whereas there are detailed mechanistic descriptions of OSI, much less is known
      about the molecular basis of CSI. Here, we review evidence for CSI in voltage
      gated cationic channels (VGCCs) and recent findings that shed light on the
      molecular mechanisms of CSI in voltage-gated K(+) (Kv) channels. Particularly,
      complementary observations suggest that the S4 voltage sensor, the S4S5 linker
      and the main S6 activation gate are instrumental in the installment of CSI in Kv4
      channels. According to this hypothesis, the voltage sensor may adopt a distinct
      conformation to drive CSI and, depending on the stability of the interactions
      between the voltage sensor and the pore domain, a closed-inactivated state
      results from rearrangements in the selectivity filter or failure of the
      activation gate to open. Kv4 channel CSI may efficiently exploit the dynamics of
      the subthreshold membrane potential to regulate spiking properties in excitable
      tissues.

PMID- 21098011
TI  - Long-term treatment with lanthanum carbonate reduces mineral and bone
      abnormalities in rats with chronic renal failure.
AB  - BACKGROUND: Lanthanum carbonate (FOSRENOL((r)), Shire Pharmaceuticals) is an
      effective non-calcium, non-resin phosphate binder for the treatment of
      hyperphosphataemia in patients with chronic kidney disease (CKD). In this study,
      we used a rat model of chronic renal failure (CRF) to examine the long-term
      effects of controlling serum phosphorus with lanthanum carbonate treatment on the
      biochemical and bone abnormalities associated with CKD-mineral and bone disorder
      (CKD-MBD). METHODS: Rats were fed a normal diet (normal renal function, NRF), or
      a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to
      receive normal diet plus vehicle or normal diet supplemented with 2% (w/w)
      lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1%
      adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine
      biochemistry were assessed, and bone histomorphometry was performed at study
      completion. RESULTS: Treatment with 0.75% adenine induced severe CRF, as
      demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia,
      elevated calcium * phosphorus product and secondary hyperparathyroidism were
      evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced
      hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05),
      and had little effect in NRF animals. Bone histomorphometry revealed a severe
      form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate
      treatment reduced the severity of the bone abnormalities observed, particularly
      woven bone formation and fibrosis. CONCLUSIONS: Long-term treatment with
      lanthanum carbonate reduced the biochemical and bone abnormalities of CKD-MBD in
      a rat model of CRF.

PMID- 21098012
TI  - Survival of elderly patients with stage 5 CKD: comparison of conservative
      management and renal replacement therapy.
AB  - BACKGROUND: Elderly patients with end-stage renal disease and severe extra-renal
      comorbidity have a poor prognosis on renal replacement therapy (RRT) and may opt
      to be managed conservatively (CM). Information on the survival of patients on
      this mode of therapy is limited. METHODS: We studied survival in a large cohort
      of CM patients in comparison to patients who received RRT. RESULTS: Over an 18
      year period, we studied 844 patients, 689 (82%) of whom had been treated by RRT
      and 155 (18%) were CM. CM patients were older and a greater proportion had high
      comorbidity. Median survival from entry into stage 5 chronic kidney disease was
      less in CM than in RRT (21.2 vs 67.1 months: P < 0.001). However, in patients
      aged > 75 years when corrected for age, high comorbidity and diabetes, the
      survival advantage from RRT was ~ 4 months, which was not statistically
      significant. Increasing age, the presence of high comorbidity and the presence of
      diabetes were independent determinants of poorer survival in RRT patients. In CM
      patients, however, age > 75 years and female gender independently predicted
      better survival. CONCLUSIONS: In patients aged > 75 years with high extra-renal
      comorbidity, the survival advantage conferred by RRT over CM is likely to be
      small. Age > 75 years and female gender predicted better survival in CM patients.
      The reasons for this are unclear.

PMID- 21098013
TI  - The relationship between serum uric acid and chronic kidney disease among
      Appalachian adults.

PMID- 21098014
TI  - Peritoneal macrophage infiltration is correlated with baseline peritoneal solute
      transport rate in peritoneal dialysis patients.
AB  - BACKGROUND: High baseline peritoneal solute transport rate is reportedly
      associated with reduced patient and technique survival in continuous peritoneal
      dialysis (PD) patients. However, the determinants of baseline peritoneal solute
      transport rate remain uncertain. The aim of this study was to investigate the
      relationship between peritoneal local inflammation, angiogenesis and systemic
      inflammation and baseline peritoneal permeability. METHODS: Peritoneal biopsy
      specimens from 42 pre-dialysis uraemic patients and 11 control individuals were
      investigated. Immunohistochemistry for CD68-positive macrophages, chymase- and
      tryptase-positive mast cells, interleukin-6 (IL-6)-positive cells, CD3-positive T
      cells, CD20-positive B cells, neutrophils and CD31- and pathologische anatomie
      Leiden-endothelium (PAL-E)-positive blood vessels in the peritoneum was
      performed. Baseline dialysate-to-plasma ratio for creatinine (D/P Cr) was
      determined within 6 months of PD induction. Clinical and laboratory parameters
      were measured at the time of peritoneal biopsy. Factors associated with
      peritoneal permeability were assessed by multiple linear regression analysis.
      RESULTS: Pre-dialysis uraemic peritoneum showed infiltration by CD68-positive
      macrophages, and mast cells, as compared with controls. Baseline D/P Cr was
      correlated with density of CD68-positive macrophages (P < 0.001), IL-6-positive
      cells (P < 0.001), CD31-positive (P < 0.05) and PAL-E-positive blood vessels (P <
      0.05) and serum albumin (P < 0.05). However, baseline peritoneal permeability was
      not correlated with infiltration by mast cells, B cells, T cells, neutrophils,
      serum C-reactive protein or other clinical factors. On multiple linear regression
      analysis, the number of CD68-positive macrophages in peritoneum was an
      independent predictor for baseline peritoneal permeability (P = 0.009).
      CONCLUSIONS: Peritoneal macrophage infiltration is predominant in uraemic
      patients and is an important factor in predicting baseline peritoneal
      permeability.

PMID- 21098015
TI  - Specific collaboration between rat membrane complement regulators Crry and CD59
      protects peritoneum from damage by autologous complement activation.
AB  - BACKGROUND: The peritoneal cavity is isolated from the outside and is usually a
      sterile environment. Patients on peritoneal dialysis (PD) have PD fluid (PDF)
      infused into the peritoneal cavity. We previously showed that unregulated
      complement activation could contribute to the development of peritoneal
      inflammation in yeast peritonitis in PD therapy. In that situation, suppression
      of local complement activation is essential to protect the host from further
      injury. The membrane complement regulators (CRegs), Crry, CD55 and CD59, are
      expressed in the rat peritoneum, especially along the mesothelial cell layer.
      METHODS: We investigated CRegs' functional roles in the peritoneal cavity using
      blocking mAb against each CReg and complement activation in different PDFs.
      RESULTS: Blockade of any single CReg did not cause spontaneous peritoneal injury
      in rat. Combined blockade of Crry and CD59 induced focal peritoneal tissue injury
      and heavy accumulation of inflammatory cells with peritoneal edema at 24 h.
      Deposits of C3 and C5b-9 were found on the peritoneal surface after combined
      blocking of Crry and CD59. Systemic complement depletion by cobra venom factor
      abrogated these inflammatory changes. When combined blockade of Crry and CD59 was
      performed with PDF of different pH and glucose concentration in rats, the
      peritoneal injuries were enhanced with lower pH and higher glucose concentration.
      These results were confirmed by in vitro experiments using primary rat
      mesothelial cell culture. CONCLUSIONS: Rat CRegs, Crry and CD59, specifically
      collaborate to control complement activation in rat peritoneum. During PD,
      impairment of CReg might contribute to the development of severe peritoneal
      inflammation.

PMID- 21098016
TI  - Mindin: a novel marker for podocyte injury in diabetic nephropathy.
AB  - BACKGROUND: GeneChip Expression Analysis was employed to survey the glomerular
      gene expression profile in a type 2 diabetes (T2D) model of KK/Ta mice fed with a
      high-calorie diet (HC), and we focused on the role of mindin (also called spondin
      2), whose expression is upregulated by HC. METHODS: Isolated glomeruli from three
      20-week-old KK/Ta mice fed with HC or a standard diet (SD) were dissected. Total
      RNA was extracted and labelled for hybridization using the Affymetrix GeneChip
      Mouse Genome 430 2.0 Array. The gene expression profile was compared between the
      HC and SD groups using GeneSpring 7.3.1 software. Mindin expression was examined
      using real-time PCR, western blot analysis and immunohistochemical staining in
      the glomeruli, cultured podocytes and urine samples of both mice and humans.
      RESULTS: Podocyte foot process effacement was observed in mice fed with HC. The
      mindin protein expression levels in mice were localized in the podocytes, and
      their levels in the glomeruli were increased in the HC group compared with the SD
      group. The levels of urinary mindin in the HC group at 16 weeks of age were also
      significantly higher than those in the SD group although albumin/creatinine ratio
      (ACR) did not differ between the groups. Furthermore, the levels in patients with
      T2D were higher than those in healthy individuals and increased gradually with
      increases in ACR. CONCLUSIONS: Mindin could be related to podocyte injury and
      appears to be an early biomarker of the progression of diabetic nephropathy.

PMID- 21098017
TI  - Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and
      glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal
      survival.
AB  - Heat shock factor 1 (HSF1) mediates the cellular response to stress to increase
      the production of heat shock protein (HSP) chaperones for proper protein folding,
      trafficking, and degradation; failure of this homeostatic mechanism likely
      contributes to neurodegeneration. We show that the neuroprotective drug riluzole
      increased the amount of HSF1 in NG108-15 neuroprogenitor cells by slowing the
      specific turnover of HSF1 and supporting a more robust and sustained activation
      of HSF1. Using Hsp70-luciferase as a functional readout of the activity of HSF1,
      we show that riluzole amplified the heat shock induction of the reporter gene
      with an optimal increase at 1 MUM. Immunocytochemical staining and Western blot
      quantitation of HSP70 in NG108-15 neuroprogenitor cells and embryonic spinal cord
      neurons provided corroborative evidence that riluzole amplified the HSF1
      dependent regulation of HSP70 expression. Parallel studies on the GLT1 glutamate
      transporter showed that riluzole increased GLT1-reporter and GLT1 protein
      expression and that the increase was enhanced by heat shock and coincident with
      the increased expression of HSP70 and HSP90. This result is consistent with the
      anti-glutamatergic profile of riluzole and the presence of multiple heat shock
      elements on the GLT1 gene promoter, suggesting that riluzole may modulate GLT1
      expression through HSF1. The increased HSP chaperones and GLT1 transporter
      blunted glutamate-induced and N-methyl D-aspartate receptor-mediated excitotoxic
      death. In summary, we show that riluzole increased the amount and activity of
      HSF1 to boost the expression of HSPs and GLT1 for neuroprotection under stress.

PMID- 21098018
TI  - Mechanism of polyubiquitin chain recognition by the human ubiquitin conjugating
      enzyme Ube2g2.
AB  - Ube2g2 is a human ubiquitin conjugating (E2) enzyme involved in the endoplasmic
      reticulum-associated degradation pathway, which is responsible for the
      identification and degradation of unfolded and misfolded proteins in the
      endoplasmic reticulum compartment. The Ube2g2-specific role is the assembly of
      Lys-48-linked polyubiquitin chains, which constitutes a signal for proteasomal
      degradation when attached to a substrate protein. NMR chemical shift perturbation
      and paramagnetic relaxation enhancement approaches were employed to characterize
      the binding interaction between Ube2g2 and ubiquitin, Lys-48-linked diubiquitin,
      and Lys-63-linked diubiquitin. Results demonstrate that ubiquitin binds to Ube2g2
      with an affinity of 90 MUM in two different orientations that are rotated by 180
      degrees  in models generated by the RosettaDock modeling suite. The binding of
      Ube2g2 to Lys-48- and Lys-63-linked diubiquitin is primarily driven by
      interactions with individual ubiquitin subunits, with a clear preference for the
      subunit containing the free Lys-48 or Lys-63 side chain (i.e. the distal
      subunit). This preference is particularly striking in the case of Lys-48-linked
      diubiquitin, which exhibits an ~3-fold difference in affinities between the two
      ubiquitin subunits. This difference can be attributed to the partial steric
      occlusion of the subunit whose Lys-48 side chain is involved in the isopeptide
      linkage. As such, these results suggest that Lys-48-linked polyubiquitin chains
      may be designed to bind certain proteins like Ube2g2 such that the terminal
      ubiquitin subunit carrying the reactive Lys-48 side chain can be positioned
      properly for chain elongation regardless of chain length.

PMID- 21098019
TI  - HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive
      oxygen species and NFkappaB.
AB  - HIV/HCV coinfection leads to accelerated hepatic fibrosis progression, with
      higher rates of cirrhosis, liver failure, and liver death than does HCV mono
      infection. However, the profibrogenic role of HIV on hepatocytes and hepatic
      stellate cells (HSC) has not been fully clarified. We hypothesized that HIV, HCV
      induce liver fibrosis through altered regulation of the production of
      extracellular matrix and matrix metalloproteinases. We examined the fibrogenesis-
      and fibrolysis-related gene activity in LX2 HSC and Huh7.5.1 cells in the
      presence of inactivated CXCR4 and CCR5 HIV, as well as HCV JFH1 virus. The role
      of reactive oxygen species (ROS) upon fibrosis gene expression was assessed using
      the ROS inhibitor. Fibrosis-related transcripts including procollagen alpha1(I)
      (CoL1A), TIMP1, and MMP3 mRNA were measured by qPCR. TIMP1 and MMP3 protein
      expression were assessed by ELISA. We found that inactivated CXCR4 HIV and CCR5
      HIV increased CoL1A, and TIMP1 expression in both HSC and Huh7.5.1 cells; the
      addition of JFH1 HCV further increased CoL1A and TIMP1 expression. CXCR4 HIV and
      CCR5 HIV induced ROS production in HSC and Huh7.5.1 cells which was further
      enhanced by JFH1 HCV. The ROS inhibitor DPI abrogated HIV-and HCV-induced CoL1A
      and TIMP1 expression. HIV and HCV-induced CoL1A and TIMP1 expression were also
      blocked by NFkappaB siRNA. Our data provide further evidence that HIV and HCV
      independently regulate hepatic fibrosis progression through the generation of
      ROS; this regulation occurs in an NFkappaB-dependent fashion. Strategies to limit
      the viral induction of oxidative stress are warranted to inhibit fibrogenesis.

PMID- 21098020
TI  - Expression of a protein phosphatase 1 inhibitor, cdNIPP1, increases CDK9
      threonine 186 phosphorylation and inhibits HIV-1 transcription.
AB  - CDK9/cyclin T1, a key enzyme in HIV-1 transcription, is negatively regulated by
      7SK RNA and the HEXIM1 protein. Dephosphorylation of CDK9 on Thr(186) by protein
      phosphatase 1 (PP1) in stress-induced cells or by protein phosphatase M1A in
      normally growing cells activates CDK9. Our previous studies showed that HIV-1 Tat
      protein binds to PP1 through the Tat Q(35)VCF(38) sequence, which is similar to
      the PP1-binding RVXF motif and that this interaction facilitates HIV-1
      transcription. In the present study, we analyzed the effect of expression of the
      central domain of nuclear inhibitor of PP1 (cdNIPP1) in an engineered cell line
      and also when cdNIPP1 was expressed as part of HIV-1 pNL4-3 in place of nef.
      Stable expression of cdNIPP1 increased CDK9 phosphorylation on Thr(186) and the
      association of CDK9 with 7SK RNA. The stable expression of cdNIPP1 disrupted the
      interaction of Tat and PP1 and inhibited HIV-1 transcription. Expression of
      cdNIPP1 as a part of the HIV-1 genome inhibited HIV-1 replication. Our study
      provides a proof-of-concept for the future development of PP1-targeting compounds
      as inhibitors of HIV-1 replication.

PMID- 21098021
TI  - Modeling the self-assembly of the cellulosome enzyme complex.
AB  - Most bacteria use free enzymes to degrade plant cell walls in nature. However,
      some bacteria have adopted a different strategy wherein enzymes can either be
      free or tethered on a protein scaffold forming a complex called a cellulosome.
      The study of the structure and mechanism of these large macromolecular complexes
      is an active and ongoing research topic, with the goal of finding ways to improve
      biomass conversion using cellulosomes. Several mechanisms involved in cellulosome
      formation remain unknown, including how cellulosomal enzymes assemble on the
      scaffoldin and what governs the population of cellulosomes created during self
      assembly. Here, we present a coarse-grained model to study the self-assembly of
      cellulosomes. The model captures most of the physical characteristics of three
      cellulosomal enzymes (Cel5B, CelS, and CbhA) and the scaffoldin (CipA) from
      Clostridium thermocellum. The protein structures are represented by beads
      connected by restraints to mimic the flexibility and shapes of these proteins.
      From a large simulation set, the assembly of cellulosomal enzyme complexes is
      shown to be dominated by their shape and modularity. The multimodular enzyme,
      CbhA, binds statistically more frequently to the scaffoldin than CelS or Cel5B.
      The enhanced binding is attributed to the flexible nature and multimodularity of
      this enzyme, providing a longer residence time around the scaffoldin. The
      characterization of the factors influencing the cellulosome assembly process may
      enable new strategies to create designers cellulosomes.

PMID- 21098022
TI  - Amino acid residues constituting the agonist binding site of the human P2X3
      receptor.
AB  - Homomeric P2X3 receptors are present in sensory ganglia and participate in pain
      perception. Amino acid (AA) residues were replaced in the four supposed
      nucleotide binding segments (NBSs) of the human (h) P2X3 receptor by alanine, and
      these mutants were expressed in HEK293 cells and Xenopus laevis oocytes. Patch
      clamp and two-electrode voltage clamp measurements as well as the Ca(2+) imaging
      technique were used to compare the concentration-response curves of the selective
      P2X1,3 agonist alpha,beta-methylene ATP obtained at the wild-type P2X3 receptor
      and its NBS mutants. Within these NBSs, certain Gly (Gly-66), Lys (Lys-63, Lys
      176, Lys-284, Lys-299), Asn (Asn-177, Asn-279), Arg (Arg-281, Arg-295), and Thr
      (Thr-172) residues were of great importance for a full agonist response. However,
      the replacement of further AAs in the NBSs by Ala also appeared to modify the
      amplitude of the current and/or [Ca(2+)](i) responses, although sometimes to a
      minor degree. The agonist potency decrease was additive after the simultaneous
      replacement of two adjacent AAs by Ala (K65A/G66A, F171A/T172A, N279A/F280A,
      F280A/R281A) but was not altered after Ala substitution of two non-adjacent AAs
      within the same NBS (F171A/N177A). SDS-PAGE in the Cy5 cell surface-labeled form
      demonstrated that the mutants appeared at the cell surface in oocytes. Thus,
      groups of AAs organized in NBSs rather than individual amino acids appear to be
      responsible for agonist binding at the hP2X3 receptor. These NBSs are located at
      the interface of the three subunits forming a functional receptor.

PMID- 21098023
TI  - Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and
      A2.
AB  - Human digestive carboxypeptidases CPA1, CPA2, and CPB1 are secreted by the
      pancreas as inactive proenzymes containing a 94-96-amino acid-long propeptide.
      Activation of procarboxypeptidases is initiated by proteolytic cleavage at the C
      terminal end of the propeptide by trypsin. Here, we demonstrate that subsequent
      cleavage of the propeptide by chymotrypsin C (CTRC) induces a nearly 10-fold
      increase in the activity of trypsin-activated CPA1 and CPA2, whereas CPB1
      activity is unaffected. Other human pancreatic proteases such as chymotrypsin B1,
      chymotrypsin B2, chymotrypsin-like enzyme-1, elastase 2A, elastase 3A, or
      elastase 3B are inactive or markedly less effective at promoting
      procarboxypeptidase activation. On the basis of these observations, we propose
      that CTRC is a physiological co-activator of proCPA1 and proCPA2. Furthermore,
      the results confirm and extend the notion that CTRC is a key regulator of
      digestive zymogen activation.

PMID- 21098024
TI  - A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for
      carboxyl-terminal proteolytic processing.
AB  - Acid sphingomyelinase (aSMase) catalyzes the hydrolysis of sphingomyelin (SM) to
      form the bioactive lipid ceramide (Cer). Notably, aSMase exists in two forms: a
      zinc (Zn(2+))-independent lysosomal aSMase (L-SMase) and a Zn(2+)-dependent
      secreted aSMase (S-SMase) that arise from alternative trafficking of a single
      protein precursor. Despite extensive investigation into the maturation and
      trafficking of aSMase, the exact identity of mature L-SMase has remained unclear.
      Here, we describe a novel mechanism of aSMase maturation involving C-terminal
      proteolytic processing within, or in close proximity to, endolysosomes. Using two
      different C-terminal-tagged constructs of aSMase (V5, DsRed), we demonstrate that
      aSMase is processed from a 75-kDa, Zn(2+)-activated proenzyme to a mature 65 kDa,
      Zn(2+)-independent L-SMase. L-SMase is recognized by a polyclonal Ab to aSMase,
      but not by anti-V5 or anti-DsRed antibodies, suggesting that the C-terminal tag
      is lost during maturation. Furthermore, indirect immunofluorescence staining
      demonstrated that mature L-SMase colocalized with the lysosomal marker LAMP1,
      whereas V5-aSMase localized to the Golgi secretory pathway. Moreover, V5-aSMase
      possessed Zn(2+)-dependent activity suggesting it may represent the common
      protein precursor of S-SMase and L-SMase. Importantly, the 65-kDa L-SMase, but
      not V5-aSMase, was sensitive to the lysosomotropic inhibitor desipramine, co
      fractionated with lysosomes, and migrated at the same M(r) as partially purified
      human aSMase. Finally, three aSMase mutants containing C-terminal Niemann-Pick
      mutations (R600H, R600P, DeltaR608) exhibited defective proteolytic maturation.
      Taken together, these results demonstrate that mature L-SMase arises from C
      terminal proteolytic processing of pro-aSMase and suggest that impaired C
      terminal proteolysis may lead to severe defects in L-SMase function.

PMID- 21098025
TI  - Attractant binding induces distinct structural changes to the polar and lateral
      signaling clusters in Bacillus subtilis chemotaxis.
AB  - Bacteria employ a modified two-component system for chemotaxis, where the
      receptors form ternary complexes with CheA histidine kinases and CheW adaptor
      proteins. These complexes are arranged in semi-ordered arrays clustered
      predominantly at the cell poles. The prevailing models assume that these arrays
      are static and reorganize only locally in response to attractant binding. Recent
      studies have shown, however, that these structures may in fact be much more
      fluid. We investigated the localization of the chemotaxis signaling arrays in
      Bacillus subtilis using immunofluorescence and live cell fluorescence microscopy.
      We found that the receptors were localized in clusters at the poles in most
      cells. However, when the cells were exposed to attractant, the number exhibiting
      polar clusters was reduced roughly 2-fold, whereas the number exhibiting lateral
      clusters distinct from the poles increased significantly. These changes in
      receptor clustering were reversible as polar localization was reestablished in
      adapted cells. We also investigated the dynamic localization of CheV, a hybrid
      protein consisting of an N-terminal CheW-like adaptor domain and a C-terminal
      response regulator domain that is known to be phosphorylated by CheA, using
      immunofluorescence. Interestingly, we found that CheV was localized predominantly
      at lateral clusters in unstimulated cells. However, upon exposure to attractant,
      CheV was found to be predominantly localized to the cell poles. Moreover, changes
      in CheV localization are phosphorylation-dependent. Collectively, these results
      suggest that the chemotaxis signaling arrays in B. subtilis are dynamic
      structures and that feedback loops involving phosphorylation may regulate the
      positioning of individual proteins.

PMID- 21098026
TI  - An archaeal tRNA-synthetase complex that enhances aminoacylation under extreme
      conditions.
AB  - Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis,
      functioning to attach the correct amino acid with its cognate tRNA molecule.
      AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase
      complexes (MSC) involved in archaeal and eukaryotic translation, although the
      precise biological role remains largely unknown. To gain further insights into
      archaeal MSCs, possible protein-protein interactions with the atypical
      Methanothermobacter thermautotrophicus seryl-tRNA synthetase (MtSerRS) were
      investigated. Yeast two-hybrid analysis revealed arginyl-tRNA synthetase
      (MtArgRS) as an interacting partner of MtSerRS. Surface plasmon resonance
      confirmed stable complex formation, with a dissociation constant (K(D)) of 250
      nM. Formation of the MtSerRS.MtArgRS complex was further supported by the ability
      of GST-MtArgRS to co-purify MtSerRS and by coelution of the two enzymes during
      gel filtration chromatography. The MtSerRS.MtArgRS complex also contained
      tRNA(Arg), consistent with the existence of a stable ribonucleoprotein complex
      active in aminoacylation. Steady-state kinetic analyses revealed that addition of
      MtArgRS to MtSerRS led to an almost 4-fold increase in the catalytic efficiency
      of serine attachment to tRNA, but had no effect on the activity of MtArgRS.
      Further, the most pronounced improvements in the aminoacylation activity of
      MtSerRS induced by MtArgRS were observed under conditions of elevated temperature
      and osmolarity. These data indicate that formation of a complex between MtSerRS
      and MtArgRS provides a means by which methanogenic archaea can optimize an early
      step in translation under a wide range of extreme environmental conditions.

PMID- 21098027
TI  - Claudin-2 forms homodimers and is a component of a high molecular weight protein
      complex.
AB  - Tight junctions are multiprotein complexes that form the fundamental physiologic
      and anatomic barrier between epithelial and endothelial cells, yet little
      information is available about their molecular organization. To begin to
      understand how the transmembrane proteins of the tight junction are organized
      into multiprotein complexes, we used blue native-PAGE (BN-PAGE) and cross-linking
      techniques to identify complexes extracted from MDCK II cells and mouse liver. In
      nonionic detergent extracts from MDCK II cells, the tight junction integral
      membrane protein claudin-2 was preferentially isolated as a homodimer, whereas
      claudin-4 was monomeric. Analysis of the interactions between chimeras of claudin
      2 and -4 are consistent with the transmembrane domains of claudin-2 being
      responsible for dimerization, and mutational analysis followed by cross-linking
      indicated that the second transmembrane domains were arranged in close proximity
      in homodimers. BN-PAGE of mouse liver membrane identified a relatively discrete
      high molecular weight complex containing at least claudin-1, claudin-2, and
      occludin; the difference in the protein complex sizes between cultured cells and
      tissues may reflect differences in tight junction protein or lipid composition or
      post-translational modifications. Our results suggest that BN-PAGE may be a
      useful tool in understanding tight junction structure.

PMID- 21098028
TI  - Binding of cyclic diguanylate in the non-catalytic EAL domain of FimX induces a
      long-range conformational change.
AB  - FimX is a multidomain signaling protein required for type IV pilus biogenesis and
      twitching motility in the opportunistic pathogen Pseudomonas aeruginosa. FimX is
      localized to the single pole of the bacterial cell, and the unipolar localization
      is crucial for the correct assembly of type IV pili. FimX contains a non
      catalytic EAL domain that lacks cyclic diguanylate (c-di-GMP) phosphodiesterase
      activity. It was shown that deletion of the EAL domain or mutation of the
      signature EVL motif affects the unipolar localization of FimX. However, it was
      not understood how the C-terminal EAL domain could influence protein localization
      considering that the localization sequence resides in the remote N-terminal
      region of the protein. Using hydrogen/deuterium exchange-coupled mass
      spectrometry, we found that the binding of c-di-GMP to the EAL domain triggers a
      long-range (~ca. 70 A) conformational change in the N-terminal REC domain and the
      adjacent linker. In conjunction with the observation that mutation of the EVL
      motif of the EAL domain abolishes the binding of c-di-GMP, the hydrogen/deuterium
      exchange results provide a molecular explanation for the mediation of protein
      localization and type IV pilus biogenesis by c-di-GMP through a remarkable
      allosteric regulation mechanism.

PMID- 21098029
TI  - SNF1-related protein kinases 2 are negatively regulated by a plant-specific
      calcium sensor.
AB  - SNF1-related protein kinases 2 (SnRK2s) are plant-specific enzymes involved in
      environmental stress signaling and abscisic acid-regulated plant development.
      Here, we report that SnRK2s interact with and are regulated by a plant-specific
      calcium-binding protein. We screened a Nicotiana plumbaginifolia Matchmaker cDNA
      library for proteins interacting with Nicotiana tabacum osmotic stress-activated
      protein kinase (NtOSAK), a member of the SnRK2 family. A putative EF-hand calcium
      binding protein was identified as a molecular partner of NtOSAK. To determine
      whether the identified protein interacts only with NtOSAK or with other SnRK2s as
      well, we studied the interaction of an Arabidopsis thaliana orthologue of the
      calcium-binding protein with selected Arabidopsis SnRK2s using a two-hybrid
      system. All kinases studied interacted with the protein. The interactions were
      confirmed by bimolecular fluorescence complementation assay, indicating that the
      binding occurs in planta, exclusively in the cytoplasm. Calcium binding
      properties of the protein were analyzed by fluorescence spectroscopy using Tb(3+)
      as a spectroscopic probe. The calcium binding constant, determined by the protein
      fluorescence titration, was 2.5 +/- 0.9 * 10(5) M(-1). The CD spectrum indicated
      that the secondary structure of the protein changes significantly in the presence
      of calcium, suggesting its possible function as a calcium sensor in plant cells.
      In vitro studies revealed that the activity of SnRK2 kinases analyzed is
      inhibited in a calcium-dependent manner by the identified calcium sensor, which
      we named SCS (SnRK2-interacting calcium sensor). Our results suggest that SCS is
      involved in response to abscisic acid during seed germination most probably by
      negative regulation of SnRK2s activity.

PMID- 21098030
TI  - Membrane-impermeable cross-linking provides evidence for homophilic, isoform
      specific binding of desmosomal cadherins in epithelial cells.
AB  - Desmosomes and adherens junctions are cadherin-based protein complexes
      responsible for cell-cell adhesion of epithelial cells. Type 1 cadherins of
      adherens junctions show specific homophilic adhesion that plays a major role in
      developmental tissue segregation. The desmosomal cadherins, desmocollin and
      desmoglein, occur as several different isoforms with overlapping expression in
      some tissues where different isoforms are located in the same desmosomes.
      Although adhesive binding of desmosomal cadherins has been investigated in a
      variety of ways, their interaction in desmosome-forming epithelial cells has not
      been studied. Here, using extracellular homobifunctional cross-linking, we
      provide evidence for homophilic and isoform-specific binding between the Dsc2,
      Dsc3, Dsg2, and Dsg3 isoforms in HaCaT keratinocytes and show that it represents
      trans interaction. Furthermore, the cross-linked adducts are present in the
      detergent-insoluble fraction, and electron microscopy shows that extracellular
      cross-linking probably occurs in desmosomes. We found no evidence for either
      heterophilic or cis interaction, but neither can be completely excluded by our
      data. Mutation of amino acid residues Trp-2 and Ala-80 that are important for
      trans interaction in classical cadherin adhesive binding abolished Dsc2 binding,
      indicating that these residues are also involved in desmosomal adhesion. These
      interactions of desmosomal cadherins may be of key importance for their ordered
      arrangement within desmosomes that we believe is essential for desmosomal
      adhesive strength and the maintenance of tissue integrity.

PMID- 21098031
TI  - Allosteric modulation of Ras-GTP is linked to signal transduction through RAF
      kinase.
AB  - Ras is a key signal transduction protein in the cell. Mutants of Gly(12) and
      Gln(61) impair GTPase activity and are found prominently in cancers. In wild type
      Ras-GTP, an allosteric switch promotes disorder to order transition in switch II,
      placing Gln(61) in the active site. We show that the "on" and "off" conformations
      of the allosteric switch can also be attained in RasG12V and RasQ61L. Although
      both mutants have similarly impaired active sites in the on state, RasQ61L
      stabilizes an anti-catalytic conformation of switch II in the off state of the
      allosteric switch when bound to Raf. This translates into more potent activation
      of the MAPK pathway involving Ras, Raf kinase, MEK, and ERK (Ras/Raf/MEK/ERK) in
      cells transfected with RasQ61L relative to RasG12V. This differential is not
      observed in the Raf-independent pathway involving Ras, phosphoinositide 3-kinase
      (PI3K), and Akt (Ras/PI3K/Akt). Using a combination of structural analysis,
      hydrolysis rates, and experiments in NIH-3T3 cells, we link the allosteric switch
      to the control of signaling in the Ras/Raf/MEK/ERK pathway, supporting a GTPase
      activating protein-independent model for duration of the Ras-Raf complex.

PMID- 21098032
TI  - Hyperosmotic stress-induced ATF-2 activation through Polo-like kinase 3 in human
      corneal epithelial cells.
AB  - Elevated extracellular solute concentration (hyperosmotic stress) perturbs cell
      function and stimulates cell responses by evoking MAPK cascades and activating AP
      1 transcription complex resulting in alterations of gene expression, cell cycle
      arrest, and apoptosis. The results presented here demonstrate that hyperosmotic
      stress elicited increases in ATF-2 phosphorylation through a novel Polo-like
      kinase 3 (Plk3) pathway in human corneal epithelial (HCE) cells. We found in
      hyperosmotic stress-induced HCE cells that Plk3 transferred to the nuclear
      compartment and was colocalized with ATF-2 in nuclei. Kinase activity of Plk3 was
      significantly activated by hyperosmotic stimulation. Further downstream, active
      Plk3 phosphorylated ATF-2 at the Thr-71 site in vivo and in vitro. Overexpression
      of Plk3 and its mutants enhanced hyperosmotic stress-induced ATF-2
      phosphorylation. In contrast, suppression of Plk3 by knocking down Plk3 mRNA
      effectively diminished the effect of hyperosmotic stress-induced ATF-2
      phosphorylation. The effect of hyperosmotic stress-induced activation of Plk3 on
      ATF-2 transcription factor function was also examined in CRE reporter
      overexpressed HCE cells. Our results for the first time reveal that hyperosmotic
      stress can activate the Plk3 signaling pathway that subsequently regulates the AP
      1 complex by directly phosphorylating ATF-2 independent from the effects of JNK
      and p38 activation.

PMID- 21098033
TI  - Syk-dependent phosphorylation of CLEC-2: a novel mechanism of hem-immunoreceptor
      tyrosine-based activation motif signaling.
AB  - The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single
      cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation
      motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the
      snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but
      is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn,
      and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of
      Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not
      altered in the presence of the Src family kinase inhibitor PP2, even though
      PLCgamma2 phosphorylation and platelet activation are abolished. A similar
      dependence of phosphorylation of CLEC-2 on Syk is also seen in response to
      stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2
      phosphorylation is also reduced in the absence of Lyn. These results provide the
      first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM
      receptor with Src family kinases playing a critical role further downstream
      through the regulation of Syk and other effector proteins, providing a new
      paradigm in signaling by YXXL-containing receptors.

PMID- 21098034
TI  - Insulin-degrading enzyme modulates the natriuretic peptide-mediated signaling
      response.
AB  - Natriuretic peptides (NPs) are cyclic vasoactive peptide hormones with high
      therapeutic potential. Three distinct NPs (ANP, BNP, and CNP) can selectively
      activate natriuretic peptide receptors, NPR-A and NPR-B, raising the cyclic GMP
      (cGMP) levels. Insulin-degrading enzyme (IDE) was found to rapidly cleave ANP,
      but the functional consequences of such cleavages in the cellular environment and
      the molecular mechanism of recognition and cleavage remain unknown. Here, we show
      that reducing expression levels of IDE profoundly alters the response of NPR-A
      and NPR-B to the stimulation of ANP, BNP, and CNP in cultured cells. IDE rapidly
      cleaves ANP and CNP, thus inactivating their ability to raise intracellular cGMP.
      Conversely, reduced IDE expression enhances the stimulation of NPR-A and NPR-B by
      ANP and CNP, respectively. Instead of proteolytic inactivation, IDE cleavage can
      lead to hyperactivation of BNP toward NPR-A. Conversely, decreasing IDE
      expression reduces BNP-mediated signaling. Additionally, the cleavages of ANP and
      BNP by IDE render them active with NPR-B and a reduction of IDE expression
      diminishes the ability of ANP and BNP to stimulate NPR-B. Our kinetic and
      crystallographic analyses offer the molecular basis for the selective degradation
      of NPs and their variants by IDE. Furthermore, our studies reveal how IDE
      utilizes its catalytic chamber and exosite to engulf and bind up to two NPs
      leading to biased stochastic, non-sequential cleavages and the ability of IDE to
      switch its substrate selectivity. Thus, the evolutionarily conserved IDE may play
      a key role in modulating and reshaping the strength and duration of NP-mediated
      signaling.

PMID- 21098035
TI  - Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic
      cell transformation.
AB  - RSK2 is a widely expressed serine/threonine kinase, and its activation enhances
      cell proliferation. Here, we report that ATF1 is a novel substrate of RSK2 and
      that RSK2-ATF1 signaling plays an important role in EGF-induced neoplastic cell
      transformation. RSK2 phosphorylated ATF1 at Ser-63 and enhanced ATF1
      transcriptional activity. Docking experiments using the crystal structure of the
      RSK2 N-terminal kinase domain combined with in vitro pulldown assays demonstrated
      that eriodictyol, a flavanone found in fruits, bound with the N-terminal kinase
      domain of RSK2 to inhibit RSK2 N-terminal kinase activity. In cells, eriodictyol
      inhibited phosphorylation of ATF1 but had no effect on the phosphorylation of
      RSK, MEK1/2, ERK1/2, p38 or JNKs, indicating that eriodictyol specifically
      suppresses RSK2 signaling. Furthermore, eriodictyol inhibited RSK2-mediated ATF1
      transactivation and tumor promoter-induced transformation of JB6 Cl41 cells.
      Eriodictyol or knockdown of RSK2 or ATF1 also suppressed Ras-mediated focus
      formation. Overall, these results indicate that RSK2-ATF1 signaling plays an
      important role in neoplastic cell transformation and that eriodictyol is a novel
      natural compound for suppressing RSK2 kinase activity.

PMID- 21098036
TI  - Packing of the extracellular domain hydrophobic core has evolved to facilitate
      pentameric ligand-gated ion channel function.
AB  - Protein function depends on conformational flexibility and folding stability.
      Loose packing of hydrophobic cores is not infrequent in proteins, as the enhanced
      flexibility likely contributes to their biological function. Here, using
      experimental and computational approaches, we show that eukaryotic pentameric
      ligand-gated ion channels are characterized by loose packing of their
      extracellular domain beta-sandwich cores, and that loose packing contributes to
      their ability to rapidly switch from closed to open channel states in the
      presence of ligand. Functional analyses of GABA(A) receptors show that increasing
      the beta-core packing disrupted GABA-mediated currents, with impaired GABA
      efficacy and slowed GABA current activation and desensitization. We propose that
      loose packing of the hydrophobic beta-core developed as an evolutionary strategy
      aimed to facilitate the allosteric mechanisms of eukaryotic pentameric ligand
      gated ion channels.

PMID- 21098037
TI  - Mechanistic studies of the autoactivation of PAK2: a two-step model of cis
      initiation followed by trans amplification.
AB  - Protein kinase activation, via autophosphorylation of the activation loop, is a
      common regulatory mechanism in phosphorylation-dependent signaling cascades.
      Despite the prevalence of this reaction and its importance in biological
      regulation, the molecular mechanisms of autophosphorylation are poorly
      understood. In this study, we developed a kinetic approach to distinguish
      quantitatively between cis- and trans-pathways in an autocatalytic reaction.
      Using this method, we have undertaken a detailed kinetic analysis for the
      autoactivation mechanism of p21-activated protein kinase 2 (PAK2). PAK2 is
      regulated in vivo and in vitro by small GTP-binding proteins, Cdc42 and Rac. Full
      activation of PAK2 requires autophosphorylation of the conserved threonine,
      Thr(402), in the activation loop of its catalytic kinase domain. Analyses of the
      time courses of substrate reaction during PAK2 autoactivation suggest that
      autophosphorylation of Thr(402) in PAK2 obeys a two-step mechanism of cis
      initiation, followed by trans amplification. The unphosphorylated PAK2 undergoes
      an intramolecular (cis) autophosphorylation on Thr(402) to produce phosphorylated
      PAK2, and this newly formed active PAK2 then phosphorylates other PAK2 molecules
      at Thr(402) in an intermolecular (trans) manner. Based on the kinetic equation
      derived, all microscopic kinetic constants for the cis and trans
      autophosphorylation have been estimated quantitatively. The advantage of the new
      method is not only its usefulness in the study of fast activation reactions, but
      its convenience in the study of substrate effects on modification reaction. It
      would be particularly useful when the regulatory mechanism of the
      autophosphorylation reaction toward certain enzymes is being assessed.

PMID- 21098038
TI  - Quantitative analysis of ERK2 interactions with substrate proteins: roles for
      kinase docking domains and activity in determining binding affinity.
AB  - Extracellular signal-regulated kinase-1 and -2 (ERK1/2) proteins regulate a
      variety of cellular functions, including cell proliferation and differentiation,
      by interacting with and phosphorylating substrate proteins. Two docking sites,
      common docking (CD/ED) domain and F-site recruitment site (FRS), on ERK proteins
      have been identified. Specific interactions with the CD/ED domain and the FRS
      occur with substrates containing a docking site for ERK and JNK, LXL (DEJL) motif
      (D-domain) and a docking site for ERK, FXF (DEF) motif (F-site), respectively.
      However, the relative contributions of the ERK docking sites in mediating
      substrate interactions that allow efficient phosphate transfer are largely
      unknown. In these studies, we provide a quantitative analysis of ERK2
      interactions with substrates using surface plasmon resonance to measure real time
      protein-protein interactions. ERK2 interacted with ELK-1 (DEF and DEJL motifs),
      RSK-1 (DEJL motif), and c-Fos (DEF motif) with K(D) values of 0.25, 0.15, and
      0.97 MUM, respectively. CD/ED domain mutations inhibited interactions with ELK-1
      and RSK-1 by 6-fold but had no effect on interactions with c-Fos. Select
      mutations in FRS residues differentially inhibited ELK-1 or c-Fos interactions
      with ERK2 but had little effect on RSK-1 interactions. Mutations in both the ED
      and FRS docking sites completely inhibited ELK-1 interactions but had no effect
      on interactions with stathmin, an ERK substrate whose docking site is unknown.
      The phosphorylation status of ERK2 did not affect interactions with RSK-1 or c
      Fos but did inhibit interactions with ELK-1 and stathmin. These studies provide a
      quantitative evaluation of specific docking domains involved in mediating
      interactions between ERK2 and protein substrates and define the contributions of
      these interactions to phosphate transfer.

PMID- 21098039
TI  - Binding of albumin promotes bacterial survival at the epithelial surface.
AB  - Human serum albumin (HSA) is the dominating protein in human plasma. Many
      bacterial species, especially streptococci, express surface proteins that bind
      HSA with high specificity and affinity, but the biological consequences of these
      protein-protein interactions are poorly understood. Group G streptococci (GGS),
      carrying the HSA-binding protein G, colonize the skin and the mucosa of the upper
      respiratory tract, mostly without causing disease. In the case of bacterial
      invasion, pro-inflammatory cytokines are released that activate the epithelium to
      produce antibacterial peptides, in particular the chemokine MIG/CXCL9. In
      addition, the inflammation causes capillary leakage and extravasation of HSA and
      other plasma proteins, environmental changes at the epithelial surface to which
      the bacteria need to respond. In this study, we found that GGS adsorbed HSA from
      both saliva and plasma via binding to protein G and that HSA bound to protein G
      bound and inactivated the antibacterial MIG/CXCL9 peptide. Another surface
      protein of GGS, FOG, was found to mediate adherence of the bacteria to pharyngeal
      epithelial cells through interaction with glycosaminoglycans. This adherence was
      not affected by activation of the epithelium with a combination of IFN-gamma and
      TNF-alpha, leading to the production of MIG/CXCL9. However, at the activated
      epithelial surface, adherent GGS were protected against killing by MIG/CXCL9
      through protein G-dependent HSA coating. The findings identify a previously
      unknown bacterial survival strategy that helps to explain the evolution of HSA
      binding proteins among bacterial species of the normal human microbiota.

PMID- 21098040
TI  - Recognition of sulfonylurea receptor (ABCC8/9) ligands by the multidrug
      resistance transporter P-glycoprotein (ABCB1): functional similarities based on
      common structural features between two multispecific ABC proteins.
AB  - ATP-sensitive K(+) (K(ATP)) channels are the target of a number of
      pharmacological agents, blockers like hypoglycemic sulfonylureas and openers like
      the hypotensive cromakalim and diazoxide. These agents act on the channel
      regulatory subunit, the sulfonylurea receptor (SUR), which is an ABC protein with
      homologies to P-glycoprotein (P-gp). P-gp is a multidrug transporter expressed in
      tumor cells and in some healthy tissues. Because these two ABC proteins both
      exhibit multispecific recognition properties, we have tested whether SUR ligands
      could be substrates of P-gp. Interaction with P-gp was assayed by monitoring
      ATPase activity of P-gp-enriched vesicles. The blockers glibenclamide,
      tolbutamide, and meglitinide increased ATPase activity, with a rank order of
      potencies that correlated with their capacity to block K(ATP) channels. P-gp
      ATPase activity was also increased by the openers SR47063 (a cromakalim analog),
      P1075 (a pinacidil analog), and diazoxide. Thus, these molecules bind to P-gp
      (although with lower affinities than for SUR) and are possibly transported by P
      gp. Competition experiments among these molecules as well as with typical P-gp
      substrates revealed a structural similarity between drug binding domains in the
      two proteins. To rationalize the observed data, we addressed the molecular
      features of these proteins and compared structural models, computerized by
      homology from the recently solved structures of murine P-gp and bacterial ABC
      transporters MsbA and Sav1866. Considering the various residues experimentally
      assigned to be involved in drug binding, we uncovered several hot spots, which
      organized spatially in two main binding domains, selective for SR47063 and for
      glibenclamide, in matching regions of both P-gp and SUR.

PMID- 21098041
TI  - Demographic and socioeconomic status differences in perceptions of difficulty
      with mobility in late life.
AB  - OBJECTIVES: This study assesses whether socioeconomic and demographic differences
      in reported mobility limitations are attributable to differential perceptions of
      mobility difficulty that result in the differential use of response categories.
      METHODS: Data come from the Social Environment and Biomarkers of Aging Study and
      its parent study, the Taiwan Longitudinal Study of Aging. Ordered probit models
      with person-specific cut-points are used to test whether, after controlling for
      underlying mobility using objective performance measures, cut-points for
      reporting mobility limitations vary across groups defined by demographic and
      socioeconomic characteristics. RESULTS: Age is the only characteristic that is
      consistently associated with the location of the cut-points for reporting
      mobility difficulty: At the same level of underlying mobility difficulty, older
      adults are more likely than younger adults are to report difficulty with all
      tasks except short walks. Other variables showed differences but only for one
      specific activity, for example, urban residents are more likely to report
      difficulty running than are rural residents with the same underlying level of
      mobility function. DISCUSSION: For most mobility activities, there are no
      systematic differences in the perception of difficulty by individual
      characteristics. Thus, for older Taiwanese adults, differences in mobility
      limitations associated with socioeconomic status are more likely to reflect
      underlying differences in function than differences in how these groups report
      the same capacity. The usual loss of mobility with age, however, reflects both a
      decrease in capacity and a lowering of the threshold for reporting difficulty.

PMID- 21098044
TI  - As it is at the end so it is at the beginning: legal challenges and new horizons
      for medicalised death and dying.

PMID- 21098042
TI  - Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis.
AB  - Several epidemiologic studies have found that smokers with chronic obstructive
      pulmonary disease (COPD), an inflammatory disease of the lung, have an increased
      risk of lung cancer compared with smokers without COPD. We have shown a causal
      role for COPD-like airway inflammation in lung cancer promotion in the
      CCSP(Cre)/LSL-K-ras(G12D) mouse model (CC-LR). In contrast, existing
      epidemiologic data do not suggest any definite association between allergic
      airway inflammation and lung cancer. To test this, CC-LR mice were sensitized to
      ovalbumin (OVA) and then challenged with an OVA aerosol weekly for 8 weeks. This
      resulted in eosinophilic lung inflammation associated with increased levels of T
      helper 2 cytokines and mucous metaplasia of airway epithelium, similar to what is
      seen in asthmatic patients. However, this type of inflammation did not result in
      a significant difference in lung surface tumor number (49 +/- 9 in OVA vs. 52 +/-
      5 in control) in contrast to a 3.2-fold increase with COPD-like inflammation.
      Gene expression analysis of nontypeable Haemophilus influenzae (NTHi)-treated
      lungs showed upregulation of a different profile of inflammatory genes, including
      interleukin 6 (IL-6), compared with OVA-treated lungs. Therefore, to determine
      the causal role of cytokines that mediate COPD-like inflammation in lung
      carcinogenesis, we genetically ablated IL-6 in CC-LR mice. This not only
      inhibited intrinsic lung cancer development (1.7-fold) but also inhibited the
      promoting effect of extrinsic COPD-like airway inflammation (2.6-fold). We
      conclude that there is a clear specificity for the nature of inflammation in lung
      cancer promotion, and IL-6 has an essential role in lung cancer promotion.

PMID- 21098043
TI  - Gi/o-coupled receptors compete for signaling to adenylyl cyclase in SH-SY5Y cells
      and reduce opioid-mediated cAMP overshoot.
AB  - Organization of G protein-coupled receptors and cognate signaling partners at the
      plasma membrane has been proposed to occur via multiple mechanisms, including
      membrane microdomains, receptor oligomerization, and protein scaffolding. Here,
      we investigate the organization of six types of Gi/o-coupled receptors
      endogenously expressed in SH-SY5Y cells. The most abundant receptor in these
      cells was the MU-opioid receptor (MOR), the activation of which occluded acute
      inhibition of adenylyl cyclase (AC) by agonists to delta-opioid (DOR),
      nociceptin/orphanin FQ peptide (NOPr), alpha2-adrenergic (alpha2AR), cannabinoid
      1, and serotonin 1A receptors. We further demonstrate that all receptor pairs
      share a common pool of AC. The MOR agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin
      (DAMGO) also occluded the ability of DOR agonist to stimulate G proteins.
      However, at lower agonist concentrations and at shorter incubation times when G
      proteins were not limiting, the relationship between MOR and DOR agonists was
      additive. The additive relationship was confirmed by isobolographic analysis.
      Long-term coadministration of MOR and DOR agonists caused cAMP overshoot that was
      not additive, suggesting that sensitization of AC mediated by these two receptors
      occurs by a common pathway. Furthermore, heterologous inhibition of AC by
      agonists to DOR, NOPr, and alpha2AR reduced the expression of cAMP overshoot in
      DAMGO-dependent cells. However, this cross-talk did not lead to heterologous
      tolerance. These results indicate that multiple receptors could be tethered into
      complexes with cognate signaling proteins and that access to shared AC by
      multiple receptor types may provide a means to prevent opioid withdrawal.

PMID- 21098045
TI  - Overlooking the criminally compassionate: what are the implications of
      prosecutorial policy on encouraging or assisting suicide?
AB  - The decision of the House of Lords in the case of Purdy compelled the Director of
      Public Prosecutions (DPP) to promulgate guidance as to the exercise of
      prosecutorial discretion with respect to those suspected of an offence under the
      Suicide Act 1961. Consequently, the Policy for Prosecutors in Respect of Cases of
      Encouraging or Assisting Suicide now sets out determining factors for potential
      culpability in encouraging or assisting suicide. This paper discusses the
      implications of the Policy, particularly with respect to the role of compassion
      as a key determining factor which effectively decriminalises acts of assisting or
      encouraging suicide in the majority of cases, despite such acts remaining
      technically criminal. Following the DPP's assertion that the location of the
      actual suicide is irrelevant to the prosecutorial decision, this article
      considers whether some elements of the Policy might belie this assertion. The
      apparently heightened risk of prosecution now faced by doctors and other
      healthcare professionals and workers is also considered. Finally, in light of the
      apparent prosecutorial endorsement of compassionate assisted suicide, this
      article questions whether we might now expect the imminent legalisation of
      assisted suicide.

PMID- 21098046
TI  - End-of-life decisions in dutch neonatology.
AB  - This contribution describes the regulation of end-of-life decisions in
      neonatology in the Netherlands. An account is given of the process of formulating
      rules, which includes a report by the Dutch Association for Paediatrics, two
      Court rulings, a report by a Consultation Group appointed by the Ministry of
      Health and a professional Protocol regulating deliberate ending of life in
      neonatology that was subsequently adopted as the regulation of this type of
      decision-making at the national level. The paper presents Dutch and comparative
      data on the attitude of the medical profession towards end-of-life decisions in
      neonatology and the frequency of such decisions in medical practice.

PMID- 21098047
TI  - The de-medicalisation of assisted dying: is a less medicalised model the way
      forward?
AB  - Although assisted dying has been most commonly presented within a medicalised
      framework, the notion of de-medicalisation is employed in this paper to suggest
      that there are emerging models of assisted dying in which some medical aspects
      assumed to be an integral part of the phenomenon are both challenged and
      diminished. The paper considers cases where relatives have facilitated a loved
      one's assisted suicide abroad, cases of assisted death in which the assistor in
      the actual suicide act is a non-medic, and the growing debate surrounding non
      medical grounds for desiring death. In evaluating the potential impact of partial
      de-medicalisation on the assisted dying debate, the argument presented is that
      whilst a de-medicalised model could well contribute to a richer understanding of
      assisted dying and a better death for the person who is assisted, there are
      cogent reasons to retain some aspects of the medicalised model and that a
      completely de-medicalised model of assisted dying is unrealistic.

PMID- 21098048
TI  - Assisted dying and the context of debate: 'medical law' versus 'end-of-life law'.
AB  - This paper provides a reflective analysis of the nature of normative critiques of
      law generally, and within medical law specifically. It first seeks to establish
      the context within which critical analysis of law and legal measures takes place,
      and develops an argument that critiques should focus on political norms. Entailed
      in this claim is the contention that positions that seek to address controversial
      social problems can not resort simply to moral philosophy. It then provides a
      brief account of political liberalism that can contain and expose normative
      constraints on questions of moral and social contention. The focus then moves to
      a more direct reflection on medico-legal analysis. Considering both medical law
      as a discipline, and the study of end-of-life issues, the argument highlights the
      range of relevant issues that must be accounted for, and addresses the question
      of whether these are well conceived as ones of medical law. It is argued that a
      political framing offers a good general analytic context, but that when working
      in legal sub-disciplines analysts risk allowing 'locally' pertinent norms to
      dominate or unduly constrain wider debate. Thus it is questioned whether 'medical
      law' provides a coherent frame for social questions related to assisted-dying.

PMID- 21098049
TI  - The case of Dr Munro: are there lessons to be learnt?

PMID- 21098050
TI  - BMP signaling promotes the growth of primary human colon carcinomas in vivo.
AB  - Human colon carcinomas (CCs) represent a growing worldwide problem. One of the
      pathways that has been negatively implicated in the genesis of CCs is triggered
      by bone morphogenetic protein (BMP) ligands, which activate BMP receptors leading
      to the function of SMAD proteins in the nucleus. BMP signaling is altered in
      familial human polyposis, and mice with compromised BMP signaling in the
      intestine develop tumors. Here, we have re-evaluated the presence and roles of
      BMP signaling in advanced sporadic human CCs, using both primary tumors and
      established cell lines, and directly modulating BMP pathway activity in a cell
      autonomous manner using constitutively active and dominant-negative BMP receptor
      Ib forms. We find evidence for active endogenous BMP signaling in all primary CC
      samples and for its role in promoting primary CC tumor growth and CC cell
      survival and proliferation in vivo in xenografts. In vitro, we also document
      autonomous and non-autonomous effects of enhanced BMP receptor activity on gap
      closure in culture, suggesting possible roles in invasion. Caution should thus be
      exerted in trying to augment or restore its activity for therapeutic purposes. In
      contrast, we raise the possibility that blockade of BMP signaling might have
      beneficial effects against at least a subset of advanced colon cancers.

PMID- 21098051
TI  - Crystal structure of Mj1640/DUF358 protein reveals a putative SPOUT-class RNA
      methyltransferase.
AB  - The proteins in DUF358 family are all bacterial proteins, which are ~200 amino
      acids long with unknown function. Bioinformatics analysis suggests that these
      proteins contain several conserved arginines and aspartates that might adopt
      SPOUT-class fold. Here we report crystal structure of Methanocaldococcus
      jannaschii DUF358/Mj1640 in complex with S-adenosyl-L-methionine (SAM) at 1.4 A
      resolution. The structure reveals a single domain structure consisting of eight
      stranded beta-sheets sandwiched by six alpha-helices at both sides. Similar to
      other SPOUT-class members, Mj1640 contains a typical deep trefoil knot at its C
      terminus to accommodate the SAM cofactor. However, Mj1640 has limited structural
      extension at its N-terminus, which is unique to this family member. Mj1640 forms
      a dimer, which is mediated by two parallel pairs of alpha-helices oriented almost
      perpendicular to each other. Although Mj1640 shares close structural similarity
      with Nep1, the significant differences in N-terminal extension domain and the
      overall surface charge distribution strongly suggest that Mj1640 might target a
      different RNA sequence. Detailed structural analysis of the SAM-binding pocket
      reveals that Asp157 or Glu183 from its own monomer or Ser43 from the associate
      monomer probably plays the catalytic role for RNA methylation.

PMID- 21098053
TI  - Overview: the role of emergent properties of complex systems in the epidemiology
      and prevention of sexually transmitted infections including HIV infection.

PMID- 21098054
TI  - A sociological interpretation of emerging properties in STI transmission
      dynamics: walk-betweenness of sexual networks.
AB  - OBJECTIVES: This study is intended to examine the role of bridges in sexually
      transmitted infection (STI) transmission dynamics as an emerging property that is
      an unintended and aggregate result of individual behaviours or preferences. It
      also provides an empirical illustration using a newly customised measure of
      bridging activities--namely, 'walk-betweenness'. METHODS: Participants in the
      Chicago Sexual Acquisition and Transmission of HIV Cooperative Agreement Program
      (SATHCAP) recruited from August 2005 through October 2006 were used in the
      analysis. They were recruited through respondent-driven bias-adjusted snowball
      sampling, beginning with six 'seed' recruiters who were given seven coded coupons
      to distribute to eligible peers for inclusion in the study: three coupons for
      drug users or men who have sex with men (MSM) regardless of drug use; three
      coupons for sexual partners; and one coupon for either a non-drug-using sex
      partner or, if the seed participant was an MSM, for a female sex partner. A walk
      betweenness score was created for each of the 77 community areas in Chicago. The
      SATHCAP questionnaire was used to ask respondents for the neighbourhood locations
      in which they had had sex in the previous 6&emsp14;months. The total number of
      respondents was 1068. RESULTS: The results of the study confirm the existence of
      hidden bridging communities in the Chicago area. Although these communities were
      essential to AIDS transmission, they might have been largely ignored because of
      their low prevalence rates. CONCLUSIONS: The role of bridging positions in STI
      transmission dynamics can be considered as an emerging property that is an
      aggregate result from individual sexual behaviours or preferences. A newly
      customised measure of bridging positions is needed to identify this property
      adequately.

PMID- 21098056
TI  - Emergent properties and structural patterns in sexually transmitted infection and
      HIV research.
AB  - BACKGROUND: Despite remarkable progress in the scientific understanding of the
      biological characteristics of the pathogens, pathogenesis and immunology, human
      sexual behaviour and population transmission dynamics, there are still
      considerable knowledge gaps regarding the heterogeneity and determinants of
      epidemics of sexually transmitted infections (STI) and HIV. To understand more
      fully the causes of STI and HIV epidemics it is necessary to reconcile individual
      and population approaches and bring together sociological and biomedical streams
      of research. METHODS: This study examined the implications of approaching the
      study of STI and HIV epidemics from the perspective that individual and
      population-level characteristics and interactions result in emergent properties
      and structural patterns that cannot be easily predicted. In addition to offering
      examples from the research literature, female sex work is analysed as an example
      of a complex adaptive system and the implications for STI and HIV epidemics are
      examined in that context. RESULTS: Previous research in this field has provided
      compelling examples of how the complex interplay of individuals and resulting
      structural patterns including sexual networks can influence the patterns of
      emergence and the trajectory of STI and HIV epidemics. CONCLUSIONS: Approaching
      the study of STI and HIV epidemics as emergent phenomena arising from complex
      interactive systems with diverse structural patterns offers a promising avenue
      for developing a more coherent understanding of these epidemics. It would also
      promote consilience between sociological, population and biomedical disciplines
      that could open new vistas for the science of public health.

PMID- 21098055
TI  - Non-monogamy and risk of infection with Chlamydia trachomatis and Trichomonas
      vaginalis among young adults and their cohabiting partners in Peru.
AB  - OBJECTIVES: To determine how patterns of non-monogamy influence prevalences of
      sexually transmitted infections (STIs) in individuals and their cohabitating sex
      partners. METHODS A 2002 survey in 24 Peruvian cities enrolled men and women aged
      18-29&emsp14;years from random household samples. The cohabiting sex partner of
      each enrolee was also enrolled until approximately 100 couples per city were
      recruited. Men provided urine and women vaginal swabs or urine for molecular
      testing for Chlamydia trachomatis and Trichomonas vaginalis; both genders
      provided blood for serological testing. RESULTS: Among 2099 females and 2052
      males providing specimens and behavioural data, 18.2% of males and 2.5% of
      females reported non-monogamy during the past year. C trachomatis was detected in
      121 females (5.8%) and 80 males (4.1%) and T vaginalis in 87 females (4.2%) and
      26 males (1.3%). Multivariate analyses showed that C trachomatis infection in
      females was significantly associated with her male partner's non-monogamy (OR
      2.02, CI 1.32 to 3.08) but not significantly with her own non-monogamy; T
      vaginalis was associated with her own non-monogamy (OR 3.11, CI 1.25 to 7.73) and
      with her partner's non-monogamy (OR 2.07, CI 1.26 to 3.42). For males, both C
      trachomatis (OR 2.17, CI 1.29 to 3.69) and T vaginalis (OR 2.49, CI 1.06 to 5.87)
      were significantly associated only with his own non-monogamy. CONCLUSIONS: Among
      cohabiting couples, male non-monogamy was common and was associated with C
      trachomatis and T vaginalis infection in himself and in his female partner,
      whereas female non-monogamy was reported infrequently and was significantly
      associated only with her own T vaginalis infection. Patterns of non-monogamy may
      guide public health interventions.

PMID- 21098057
TI  - The distribution of chlamydia, gonorrhoea and syphilis cases across states and
      counties in the USA, 2007.
AB  - OBJECTIVES: To examine the distribution of chlamydia, gonorrhoea and syphilis in
      the USA through the use of Lorenz curves and Gini coefficients. METHODS: The
      distribution of three sexually transmitted diseases (STD; chlamydia, gonorrhoea
      and primary and secondary syphilis) was examined across states and counties in
      the USA in 2007, based on reported case numbers. Gini coefficients, which can
      range from 0 (equality in STD rates across geographical units) to 1 (complete
      inequality such that all STD occur in one geographical unit) were calculated.
      RESULTS: Overall, chlamydia was the most evenly distributed and syphilis was the
      most concentrated of the three STD examined. The Gini coefficients for chlamydia,
      gonorrhoea and syphilis were 0.121, 0.255 and 0.334, respectively, when examined
      across states, and 0.319, 0.494 and 0.630, respectively, when examined across
      counties. Differences in Gini coefficients were observed when the STD
      distributions were examined by sex, race/ethnicity and age group. CONCLUSIONS:
      The use of Lorenz curves and Gini coefficients can help to assess inequalities in
      the distribution of STD, to gauge the suitability of geographically targeted
      interventions, and to help in determining the epidemic phase of STD. Having a
      better understanding of the disparities in the distribution of STD across states
      and counties by sex, race/ethnicity and age group might help in understanding why
      disparities in STD rates exist across different groups and in developing
      interventions to address these disparities.

PMID- 21098058
TI  - Republished paper: Populations and partnerships: insights from metapopulation and
      pair models into the epidemiology of gonorrhoea and other sexually transmitted
      infections.
AB  - BACKGROUND: Models of sexually transmitted infection (STI) transmission can offer
      insights as to why gonorrhoea and other STIs are disproportionately concentrated
      in epidemiologically distinct subpopulations. METHODS: We highlight two different
      constructs for modelling STIs by drawing on previously published work on pair and
      metapopulation models, and reanalysed partnership data from the National Survey
      of Sexual Attitudes and Lifestyles II (NATSAL II) in the UK. RESULTS: Pair models
      account for intrapair reinfections and are necessary to illustrate the importance
      of partnership dynamics. The pair modelling framework suggests that a key
      determinant of transmission is the length of time or 'gap' between partnerships,
      and that partnerships of medium length can potentially be more efficient for
      gonococcal transmission than the shortest partnerships. As for the metapopulation
      framework, one key insight is that the epidemiology of gonorrhoea is possibly
      being driven by subpopulations with higher than average concentrations of
      individuals with high sexual risk activity. The reanalysis of data on sexual
      behaviour in the UK shows that well recognised population subgroups at higher
      risk of gonorrhoea do also have higher levels of risk behaviour, such as a higher
      average number of new partners per year, as well as a higher prevalence of
      concurrent partnerships and short gaps before partnerships. RESULTS: The
      concentration of risk behaviour in key population subgroups may be leading to
      self-sustaining pockets of transmission for STIs. Combinations of partnership
      behaviours at the level of population subgroups should be a subject of future
      empirical research as well as modelling efforts.

PMID- 21098059
TI  - From individuals to complex systems: exploring the sexual networks of men who
      have sex with men in three cities of Karnataka, India.
AB  - INTRODUCTION: Research on the HIV vulnerability of men who have sex with men
      (MSM) in India has tended to focus on aggregates of individual risk behaviours.
      However, such an approach often overlooks the complexities in the sexual networks
      that ultimately underpin patterns of spread. This paper analyses a set of sexual
      contact network (SCN) snapshots in relation to ethnographic findings to
      reorientate individual-level explanations of risk behaviour in terms of more
      complex systems. METHODS: Fifteen community researchers conducted a 2-month
      ethnographic study in three cities in Karnataka to generate descriptions of the
      risk environments inhabited by MSM. SCNs were reconstructed by two methods.
      First, initial participants, defined as nodes of various sexual networks, were
      purposively sampled. In each site, six nodes brought in three sexual partners
      separately as participants. In all sites, 72 participants completed 431 surveys
      for their 7-day sexual partners. Second, each site determined four groups
      representing various sexual networks, each group containing four individuals. In
      all sites, 48 participants completed 334 surveys for their regular sexual
      partner. RESULTS: Considerable differences were observed between sites for
      practically all included behavioural variables. On their own, these
      characteristics yielded contradictory interpretations with respect to
      understanding contrasts in HIV prevalence at each site. However, viewing these
      variables in relation to SCNs and ethnographic data produced non-linear
      interpretations of HIV vulnerability which suggested importance to local
      interventions. CONCLUSION: SCN data may be used with existing data on risk
      behaviour and the structural determinants of vulnerability to re-tailor more
      tightly focused interventions.

PMID- 21098060
TI  - Emergent properties of HIV risk among injection drug users in Tallinn, Estonia:
      synthesis of individual and neighbourhood-level factors.
AB  - OBJECTIVES: HIV/AIDS risk is embodied within multiple levels including structural
      and social levels. The aim of this study was to assess the effects of
      neighbourhood characteristics on HIV prevalence among injection drug users (IDU)
      residing in the area of Tallinn, Estonia in 2007. METHODS: A cross-sectional,
      multilevel design collecting individual-level data--a behaviour survey including
      data on self-reported residency and HIV antibody testing among 350 IDU and
      neighbourhood-level data--aggregate measures on socio-demo-economic residential
      characteristics from the 2000 Estonian census. Geocoding and multilevel modelling
      analysis was employed. RESULTS: Among the 350 IDU recruited, earlier age at first
      injection, fentanyl as the main injection drug, receptive syringe sharing, main
      income source other than legal employment and ever attended a syringe exchange
      programme remained significantly associated with increased odds of anti-HIV
      positivity in the multivariable analysis involving individual effects with no
      predictors at the neighbourhood level. In the multilevel model, individual
      (earlier at IDU initiation AOR 1.86, 95% CI 1.01 to 3.44; injecting opioids AOR
      4.43, 95% CI 2.74 to 7.18; receptive syringe sharing AOR 2.51, 95% CI 1.86 to
      3.37; main income source other than work AOR 2.04, 95% CI 1.32 to 3.14; ever
      attended a syringe exchange programme AOR 2.58, 95% CI 1.83 to 3.61) and
      neighbourhood level (higher unemployment rate AOR 5.95, 95% CI 2.47 to 14.31;
      greater residential change AOR 1.89, 95% CI 1.09 to 3.26) emerged as significant
      predictors of individual HIV-positive status. CONCLUSIONS: Our results indicate
      that both individual-level and emergent neighbourhood-level factors contribute to
      HIV risk among IDU and are amenable for preventive interventions.

PMID- 21098061
TI  - Remodelling core group theory: the role of sustaining populations in HIV
      transmission.
AB  - BACKGROUND AND OBJECTIVES: Core group theory describes the central role of groups
      with high rates of sexual partner change in HIV transmission. Research
      illustrates the heterogeneous and dynamic nature of commercial sex, and that some
      men involved in the organisation or policing of sex work regularly have sex with
      sex workers. These findings are used to explore gaps in core group theory.
      METHODS: Evidence from developing countries on the duration that women sell and
      men buy sex was reviewed. Simple compartmental dynamic models were used to derive
      analytical expressions for the relative HIV equilibrium levels among sex workers
      and partners, incorporating partner change rates and duration in commercial sex
      settings. Simulations explored the degree to which HIV infection can be
      attributable to men with low partner change rates who remain in sex work settings
      for long periods, and their influence on the impact of HIV intervention. RESULTS:
      Partner change rates and duration of time in a setting determine equilibrium HIV
      levels. Modelling projections suggest that men with low mobility can
      substantially contribute to HIV prevalence among sex workers, especially in
      settings with prevalences <50%. This effect may reduce the impact of sex-worker
      interventions on HIV incidence in certain scenarios by one-third. Reductions in
      impact diminish at higher sex-worker prevalences. CONCLUSION: In commercial sex
      settings, patterns of HIV risk and transmission are influenced by both partner
      change rates and duration in a setting. The latter is not reflected in classic
      core group theory. Men who control the sex industry and regular clients may form
      an important 'sustaining population' that increases infection and undermines the
      impact of intervention. Intervention activities should include these groups, and
      examine the social organisation of sex work that underpins many of these
      relationships.

PMID- 21098064
TI  - The need for public engagement in choosing health priorities.

PMID- 21098062
TI  - Reducing the pain of childhood vaccination: an evidence-based clinical practice
      guideline.

PMID- 21098067
TI  - Reducing the pain of childhood vaccination: an evidence-based clinical practice
      guideline (summary).

PMID- 21098066
TI  - Six-month exercise training program to treat post-thrombotic syndrome: a
      randomized controlled two-centre trial.
AB  - BACKGROUND: Exercise training may have the potential to improve post-thrombotic
      syndrome, a frequent, chronic complication of deep venous thrombosis. We
      conducted a randomized controlled two-centre pilot trial to assess the
      feasibility of a multicentre-based evaluation of a six-month exercise training
      program to treat post-thrombotic syndrome and to obtain preliminary data on the
      effectiveness of such a program. METHODS: Patients were randomized to receive
      exercise training (a six-month trainer-supervised program) or control treatment
      (an education session with monthly phone follow-ups). Levels of eligibility,
      consent, adherence and retention were used as indicators of study feasibility.
      Primary outcomes were change from baseline to six months in venous disease
      specific quality of life (as measured using the Venous Insufficiency
      Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire)
      and severity of post-thrombotic syndrome (as measured by scores on the Villalta
      scale) in the exercise training group versus the control group, assessed by t
      tests. Secondary outcomes were change in generic quality of life (as measured
      using the Short-Form Health Survey-36 [SF-36] questionnaire), category of
      severity of post-thrombotic syndrome, leg strength, leg flexibility and time on
      treadmill. RESULTS: Of 95 patients with post-thrombotic syndrome, 69 were
      eligible, 43 consented and were randomized, and 39 completed the study. Exercise
      training was associated with improvement in VEINES-QOL scores (exercise training
      mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2;
      difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the
      Villalta scale (exercise training mean change -3.6, SD 3.7 v. control mean change
      -1.6, SD 4.3; difference -2.0, 95% CI -4.6 to 0.6; p = 0.14). Most secondary
      outcomes also showed greater improvement in the exercise training group.
      INTERPRETATION: Exercise training may improve post-thrombotic syndrome. It would
      be feasible to definitively evaluate exercise training as a treatment for post
      thrombotic syndrome in a large multicentre trial.

PMID- 21098068
TI  - Discoloration of nail beds and skin from minocycline.

PMID- 21098070
TI  - Preparing for the inevitable.

PMID- 21098069
TI  - An avoidable transmission of HIV from mother to child.

PMID- 21098071
TI  - Demands made for inquiry into operations of reproductive health agency.

PMID- 21098072
TI  - China searches for best medicine for ailing scientific journals.

PMID- 21098073
TI  - Canadian baby boomers shirk safe sex.

PMID- 21098074
TI  - Value of hospital standardized mortality ratio unclear, administrators say.

PMID- 21098075
TI  - Should I prescribe sunlight instead of vitamin D?

PMID- 21098076
TI  - Flipside of the dialysis argument.

PMID- 21098077
TI  - Decriminalize prostituted women.

PMID- 21098078
TI  - Vitamin D for mental health and cognition.

PMID- 21098079
TI  - Training for internal medicine.

PMID- 21098080
TI  - A novel proteomics approach to identify SUMOylated proteins and their
      modification sites in human cells.
AB  - The small ubiquitin-related modifier (SUMO) is a small group of proteins that are
      reversibly attached to protein substrates to modify their functions. The large
      scale identification of protein SUMOylation and their modification sites in
      mammalian cells represents a significant challenge because of the relatively
      small number of in vivo substrates and the dynamic nature of this modification.
      We report here a novel proteomics approach to selectively enrich and identify
      SUMO conjugates from human cells. We stably expressed different SUMO paralogs in
      HEK293 cells, each containing a His(6) tag and a strategically located tryptic
      cleavage site at the C terminus to facilitate the recovery and identification of
      SUMOylated peptides by affinity enrichment and mass spectrometry. Tryptic
      peptides with short SUMO remnants offer significant advantages in large scale
      SUMOylome experiments including the generation of paralog-specific fragment ions
      following CID and ETD activation, and the identification of modified peptides
      using conventional database search engines such as Mascot. We identified 205
      unique protein substrates together with 17 precise SUMOylation sites present in
      12 SUMO protein conjugates including three new sites (Lys-380, Lys-400, and Lys
      497) on the protein promyelocytic leukemia. Label-free quantitative proteomics
      analyses on purified nuclear extracts from untreated and arsenic trioxide-treated
      cells revealed that all identified SUMOylated sites of promyelocytic leukemia
      were differentially SUMOylated upon stimulation.

PMID- 21098081
TI  - Smoking status and immunoglobulin E seropositivity to workplace allergens.
AB  - BACKGROUND: Detection of serum-specific immunoglobulin E (IgE) can be helpful in
      the diagnosis of work-related allergic conditions. There have been conflicting
      reports regarding any association between smoking and specific IgE levels. AIMS:
      To establish whether a relationship exists between smoking status and the outcome
      of specific IgE tests to workplace allergens. METHODS: The Health and Safety
      Laboratory provides test services for workplace allergens and the request form
      used collects data on smoking status. Laboratory results of 695 subjects who had
      undergone specific IgE tests were examined by information on smoking. RESULTS:
      Smokers were more likely than non-smokers to have positive specific IgE tests (P
      < 0.05). Smoking was the only independent predictor of a positive specific IgE
      test in logistic regression, with odds ratio of 2.39 (95% confidence interval
      1.01-5.65, P < 0.05) for IgE seropositivity. Allergen subgroups also showed a
      positive association with smoking and in particular for high molecular weight
      allergens. CONCLUSIONS: Being a current smoker is a risk factor for sensitization
      to workplace allergens especially for those of high molecular weight. Workplace
      well-being activities may make use of such information for smoking cessation
      programmes and emphasizing the importance of allergen exposure control.
      Collaboration between testing laboratories may provide useful datasets for
      further analysis.

PMID- 21098083
TI  - The 'father of IVF' and a founding father of ESHRE.

PMID- 21098082
TI  - Increased uptake of [123I]meta-iodobenzylguanidine, [18F]fluorodopamine, and
      [3H]norepinephrine in mouse pheochromocytoma cells and tumors after treatment
      with the histone deacetylase inhibitors.
AB  - [131I]meta-iodobenzylguanidine ([131I]MIBG) is the most commonly used treatment
      for metastatic pheochromocytoma and paraganglioma. It enters the chromaffin cells
      via the membrane norepinephrine transporter; however, its success has been
      modest. We studied the ability of histone deacetylase (HDAC) inhibitors to
      enhance [123I]MIBG uptake by tumors in a mouse metastatic pheochromocytoma model.
      HDAC inhibitors are known to arrest growth, induce differentiation and apoptosis
      in various cancer cells, and further inhibit tumor growth. We report the in vitro
      and in vivo effects of two HDAC inhibitors, romidepsin and trichostatin A, on the
      uptake of [(3)H]norepinephrine, [123I]MIBG, and [(18)F]fluorodopamine in a mouse
      model of metastatic pheochromocytoma. The effects of both inhibitors on
      norepinephrine transporter activity were assessed in mouse pheochromocytoma (MPC)
      cells by using the transporter-blocking agent desipramine and the vesicular
      blocking agent reserpine. HDAC inhibitors increased [(3)H]norepinephrine,
      [123I]MIBG, and [(18)F]fluorodopamine uptake through the norepinephrine
      transporter in MPC cells. In vivo, inhibitor treatment resulted in significantly
      increased uptake of [(18)F]fluorodopamine positron emission tomography (PET) in
      pheochromocytoma liver metastases (19.1 +/- 3.2% injected dose per gram of tumor
      (%ID/g) compared to liver metastases in pretreatment scans 5.9 +/- 0.6%;
      P<0.001). Biodistribution analysis after inhibitors treatment confirmed the PET
      results. The uptake of [(123)I]MIBG was significantly increased in liver
      metastases 9.5 +/- 1.1% compared to 3.19 +/- 0.4% in untreated control liver
      metastases (P<0.05). We found that HDAC inhibitors caused an increase in the
      amount of norepinephrine transporter expressed in tumors. HDAC inhibitors may
      enhance the therapeutic efficacy of [(131)I]MIBG treatment in patients with
      advanced malignant pheochromocytoma and paraganglioma.

PMID- 21098084
TI  - Robert G. Edwards, Co-founder of ESHRE and Founding Editor of the ESHRE journals,
      receives Nobel Prize.

PMID- 21098085
TI  - Letter of appreciation: to Bob Edwards, Founding Editor, from Andre Van
      Steirteghem, Editor-in-Chief, Human Reproduction.

PMID- 21098086
TI  - The early days of 'Human Reproduction'.

PMID- 21098088
TI  - Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic
      microRNA signatures in the sera of prostate cancer patients.
AB  - Recent prostate-specific antigen-based screening trials indicate an urgent need
      for novel and noninvasive biomarker identification strategies to improve the
      prediction of prostate cancer behavior. Noncoding microRNAs (miRNA) in the serum
      and plasma have been shown to have potential as noninvasive markers for
      physiologic and pathologic conditions. To identify serum miRNAs that diagnose and
      correlate with the prognosis of prostate cancer, we developed a multiplex
      quantitative reverse transcription PCR method involving the purification of
      multiplex PCR products followed by uniplex analysis on a microfluidics chip to
      evaluate 384 human miRNAs. Using Dgcr8 and Dicer knockout (small RNA-deficient)
      mouse ES cells as the benchmark, we confirmed the validity of our technique and
      uncovered a considerable lack of accuracy in previously published methods.
      Profiling 48 sera from healthy men and untreated prostate cancer patients with
      differing CAPRA scores, we identified miRNA signatures that allow us to diagnose
      cancer patients and correlate with a prognosis. These serum signatures include
      oncogenic and tumor-suppressive miRNAs, suggesting functional roles in prostate
      cancer progression.

PMID- 21098087
TI  - CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK
      is required for androgen-dependent migration of prostate cancer cells.
AB  - While patients with advanced prostate cancer initially respond favorably to
      androgen ablation therapy, most experience a relapse of the disease within 1-2
      years. Although hormone-refractory disease is unresponsive to androgen
      deprivation, androgen receptor (AR)-regulated signaling pathways remain active
      and are necessary for cancer progression. Thus, both AR itself and the processes
      downstream of the receptor remain viable targets for therapeutic intervention.
      Microarray analysis of multiple clinical cohorts showed that the serine/threonine
      kinase Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) is both
      highly expressed in the prostate and further elevated in prostate cancers. Using
      cellular models of prostate cancer, we have determined that androgens (a)
      directly increase the expression of a CaMKKbeta splice variant and (b) increase
      functional CaMKKbeta protein levels as determined by the phosphorylation of both
      CaMKI and AMP-activated protein kinase (AMPK), two of CaMKKbeta's primary
      substrates. Importantly, inhibition of the CaMKKbeta-AMPK, but not CaMKI,
      signaling axis in prostate cancer cells by pharmacological inhibitors or siRNA
      mediated knockdown blocks androgen-mediated migration and invasion. Conversely,
      overexpression of CaMKKbeta alone leads to both increased AMPK phosphorylation
      and cell migration. Given the key roles of CaMKKbeta and AMPK in the biology of
      prostate cancer cells, we propose that these enzymes are potential therapeutic
      targets in prostate cancer.

PMID- 21098089
TI  - How good are current approaches to nonclinical evaluation of abuse and
      dependence?
AB  - Nonclinical assessment of drug abuse and dependence is the subject of several
      recent regulatory guidelines, which are generally aligned on the methods to be
      employed. The most direct approach to assessing reinforcing properties of a drug
      is the self-administration procedure whereby animals can initiate intravenous
      injections of the test substance, something they readily do with prototypic drugs
      of abuse. Complications arise because there is no standardized procedure for
      evaluating substances with differing potencies, reinforcement properties, or
      pharmacokinetics. Moreover, the choice of training substance, species, and
      procedural parameters can radically affect the outcome. Apart from the lower cost
      of rats, primates present several advantages for self-administration studies with
      similarity to human pharmacokinetics in particular. The most powerful method for
      assessing similarities between a test substance and a prototypic drug of abuse is
      the drug discrimination procedure. In contrast to self-administration, drug
      discrimination is pharmacologically very specific, often reflecting functional
      activity at receptor level. Dependence is assessed by the occurrence of
      withdrawal effects on drug discontinuation. Although conceptually simple,
      interpretation can be complicated by factors such as duration and frequency of
      administration and observations as well as the choice of end points. Telemetry
      allows continuous observation of multiple parameters during withdrawal, thereby
      increasing sensitivity. Presently available tools identify all substances known
      to cause abuse or dependence, with little risk of false-positives. It remains
      unclear, however, how predictive these models are with entirely novel substances.
      Nonetheless, drug abuse/dependence is an area of safety pharmacology where the
      predictive value of animal models is remarkably high.

PMID- 21098090
TI  - Inhibition of NADPH oxidases prevents chronic ethanol-induced bone loss in female
      rats.
AB  - Previous in vitro data suggest that ethanol (EtOH) activates NADPH oxidase (Nox)
      in osteoblasts leading to accumulation of reactive oxygen species (ROS). This
      might be a mechanism underlying inhibition of bone formation and increased bone
      resorption observed in vivo after EtOH exposure. In a rat model in which cycling
      females were infused intragastrically with EtOH-containing liquid diets, EtOH
      significantly decreased bone formation and stimulated osteoblast-dependent
      osteoclast differentiation. These effects were reversed by exogenous 17-beta
      estradiol coadministration. Moreover, coadministration of N-acetyl cysteine
      (NAC), an antioxidant, or diphenylene iodonium (DPI), a specific Nox inhibitor,
      also abolished chronic EtOH-associated bone loss. EtOH treatment up-regulated
      mRNA levels of Nox1, 2, 4, and the receptor activator of nuclear factor-kappaB
      ligand (RANKL), an essential factor for differentiation of osteoclasts in bone.
      Protein levels of Nox4, a major Nox isoform expressed in nonphagocytic cells, was
      also up-regulated by EtOH in bone. 17-beta-Estradiol, NAC, and DPI were able to
      normalize EtOH-induced up-regulation of Nox and RANKL. In vitro experiments
      demonstrated that EtOH directly up-regulated Nox expression in osteoblasts.
      Pretreatment of osteoblasts with DPI eliminated EtOH-induced RANKL promoter
      activity. Furthermore, EtOH induced RANKL gene expression, and RANKL promoter
      activation in osteoblasts was ROS-dependent. These data suggest that inhibition
      of Nox expression and activity may be critical for prevention of chronic EtOH
      induced osteoblast-dependent bone loss.

PMID- 21098091
TI  - Amelioration of neuropathic pain by novel transient receptor potential vanilloid
      1 antagonist AS1928370 in rats without hyperthermic effect.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is activated by a variety of
      stimulations, such as endogenous ligands and low pH, and is believed to play a
      role in pain transmission. TRPV1 antagonists have been reported to be effective
      in several animal pain models; however, some compounds induce hyperthermia in
      animals and humans. We discovered the novel TRPV1 antagonist (R)-N-(1-methyl-2
      oxo-1,2,3,4-tetrahydro-7-quinolyl)-2-[(2-methylpyrrolidin-1-yl)methyl]biphenyl-4
      carboxamide (AS1928370) in our laboratory. AS1928370 bound to the resiniferatoxin
      binding site on TRPV1 and inhibited capsaicin-mediated inward currents with an
      IC50 value of 32.5 nM. Although AS1928370 inhibited the capsaicin-induced Ca2(+)
      flux in human and rat TRPV1-expressing cells, the inhibitory effect on proton
      induced Ca2(+) flux was extremely small. In addition, AS1928370 showed no
      inhibitory effects on transient receptor potential vanilloid 4, transient
      receptor potential ankyrin 1, and transient receptor potential melastatin 8 in
      concentrations up to 10 MUM. AS1928370 improved capsaicin-induced secondary
      hyperalgesia and mechanical allodynia in an L5/L6 spinal nerve ligation model in
      rats with respective ED50 values of 0.17 and 0.26 mg/kg p.o. Furthermore,
      AS1928370 alleviated inflammatory pain in a complete Freund's adjuvant model at
      10 mg/kg p.o. AS1928370 had no effect on rectal body temperature up to 10 mg/kg
      p.o., although a significant hypothermic effect was noted at 30 mg/kg p.o. In
      addition, AS1928370 showed no significant effect on motor coordination. These
      results suggest that blockage of the TRPV1 receptor without affecting the proton
      mediated TRPV1 activation is a promising approach to treating neuropathic pain
      because of the potential wide safety margin against hyperthermic effects. As
      such, compounds such as ASP1928370 may have potential as new analgesic agents for
      treating neuropathic pain.

PMID- 21098092
TI  - Plexin-A4-semaphorin 3A signaling is required for Toll-like receptor- and sepsis
      induced cytokine storm.
AB  - Plexins and semaphorins are ligand-receptor pairs that serve as guidance
      molecules in the nervous system and play some roles in immunity. Plexins are
      similar to the Toll-like receptors (TLRs) in their evolutionary conservation from
      flies to mammals. By studying plexin-A4-deficient (Plxna4(-/-)) innate immune
      cells, in this study we show a novel influence of plexin-A4 on TLR signaling.
      Plxna4(-/-) cells exhibit defective inflammatory cytokine production upon
      activation by a spectrum of TLR agonists and bacteria. Plexin-A4 is required for
      TLR-induced activation of the small guanosine triphosphate hydrolase (GTPase)
      Rac1 (ras-related C3 botulinum toxin substrate 1). Rac1 activation is accompanied
      by JNK (c-Jun N-terminal kinase) and NF-kappaB activation, culminating in TLR
      induced binding of NF-kappaB and AP-1 to the promoters of inflammatory cytokines.
      Plxna4(-/-) mice are remarkably resistant to TLR agonist-induced inflammation and
      polymicrobial peritonitis caused by cecal ligation and puncture. Administration
      of a ligand of plexin-A4, Sema3A (semaphorin 3A), exacerbates the cytokine storm
      caused by TLR agonists and bacterial sepsis. TLR engagement can induce Sema3A
      expression, thus completing an autocrine loop. These findings expand the role of
      plexins to TLR signaling and suggest plexin-A4 and Sema3A as new intervention
      points for treating sepsis.

PMID- 21098093
TI  - IL-27 supports germinal center function by enhancing IL-21 production and the
      function of T follicular helper cells.
AB  - Maturation and selection of high-affinity B cell clones in the germinal center
      (GC) relies on support from T follicular helper (T(FH)) cells. T(FH) cells are
      characterized by their localization to the B cell follicle and their high
      expression of the costimulatory molecules ICOS and PD1 and the cytokine IL-21,
      which promotes immunoglobulin (Ig) class switching and production by B cells. We
      show that the heterodimeric cytokine IL-27 is critical for the function of T(FH)
      cells and for normal and pathogenic GC responses. IL-27 signaling to T cells
      results in the production of IL-21, a known autocrine factor for the maintenance
      of T(FH) cells, in a STAT3-dependent manner. IL-27 also enhances the survival of
      activated CD4(+) T cells and the expression of T(FH) cell phenotypic markers. In
      vivo, expression of the IL-27Ralpha chain is required to support IL-21 production
      and T(FH) cell survival in a T cell-intrinsic manner. The production of high
      affinity antibodies is reduced, and pristane-elicited autoantibodies and
      glomerulonephritis are significantly diminished, in Il27ra(-/-) mice. Together,
      our data show a nonredundant role for IL-27 in the development of T cell
      dependent antibody responses.

PMID- 21098094
TI  - VEGF receptor signaling links inflammation and tumorigenesis in colitis
      associated cancer.
AB  - Whereas the inhibition of vascular endothelial growth factor (VEGF) has shown
      promising results in sporadic colon cancer, the role of VEGF signaling in colitis
      associated cancer (CAC) has not been addressed. We found that, unlike sporadic
      colorectal cancer and control patients, patients with CAC show activated VEGFR2
      on intestinal epithelial cells (IECs). We then explored the function of VEGFR2 in
      a murine model of colitis-associated colon cancer characterized by increased
      VEGFR2 expression. Epithelial cells in tumor tissue expressed VEGFR2 and
      responded to VEGF stimulation with augmented VEGFR2-mediated proliferation.
      Blockade of VEGF function via soluble decoy receptors suppressed tumor
      development, inhibited tumor angiogenesis, and blocked tumor cell proliferation.
      Functional studies revealed that chronic inflammation leads to an up-regulation
      of VEGFR2 on IECs. Studies in conditional STAT3 mutant mice showed that VEGFR
      signaling requires STAT3 to promote epithelial cell proliferation and tumor
      growth in vivo. Thus, VEGFR-signaling acts as a direct growth factor for tumor
      cells in CAC, providing a molecular link between inflammation and the development
      of colon cancer.

PMID- 21098095
TI  - Transient activation of c-MYC expression is critical for efficient platelet
      generation from human induced pluripotent stem cells.
AB  - Human (h) induced pluripotent stem cells (iPSCs) are a potentially abundant
      source of blood cells, but how best to select iPSC clones suitable for this
      purpose from among the many clones that can be simultaneously established from an
      identical source is not clear. Using an in vitro culture system yielding a
      hematopoietic niche that concentrates hematopoietic progenitors, we show that the
      pattern of c-MYC reactivation after reprogramming influences platelet generation
      from hiPSCs. During differentiation, reduction of c-MYC expression after initial
      reactivation of c-MYC expression in selected hiPSC clones was associated with
      more efficient in vitro generation of CD41a(+)CD42b(+) platelets. This effect was
      recapitulated in virus integration-free hiPSCs using a doxycycline-controlled c
      MYC expression vector. In vivo imaging revealed that these CD42b(+) platelets
      were present in thrombi after laser-induced vessel wall injury. In contrast,
      sustained and excessive c-MYC expression in megakaryocytes was accompanied by
      increased p14 (ARF) and p16 (INK4A) expression, decreased GATA1 expression, and
      impaired production of functional platelets. These findings suggest that the
      pattern of c-MYC expression, particularly its later decline, is key to producing
      functional platelets from selected iPSC clones.

PMID- 21098096
TI  - Milk sialyllactose influences colitis in mice through selective intestinal
      bacterial colonization.
AB  - Milk oligosaccharides contribute to the development of the intestinal environment
      by acting as decoy receptors for pathogens and as prebiotics, which promote the
      colonization of commensal bacteria. Here, using alpha2,3- and alpha2,6
      sialyltransferase-deficient mice, we investigated the role of the sialylated milk
      oligosaccharides sialyl(alpha2,3)lactose and sialyl(alpha2,6)lactose on mucosal
      immunity. The exposure of newborn mice to milk containing or deficient in
      sialyllactose had no impact on the development of mucosal leukocyte populations.
      However, when challenged by dextran sulfate sodium (DSS) in drinking water, adult
      mice that had been fostered on sialyl(alpha2,3)lactose-deficient milk were more
      resistant to colitis compared with mice fostered on normal milk or
      sialyl(alpha2,6)lactose-deficient milk. Analysis of intestinal microbiota showed
      different colonization patterns depending on the presence or absence of
      sialyl(alpha2,3)lactose in the milk. Germ-free mice reconstituted with intestinal
      microbiota isolated from mice fed on sialyl(alpha2,3)lactose-deficient milk were
      more resistant to DSS-induced colitis than germ-free mice reconstituted with
      standard intestinal microbiota. Thus, exposure to sialyllactose during infancy
      affects bacterial colonization of the intestine, which influences the
      susceptibility to DSS-induced colitis in adult mice.

PMID- 21098097
TI  - Networking erythropoiesis.
AB  - A relatively small cadre of lineage-restricted transcription factors largely
      orchestrates erythropoiesis, but how these nuclear factors interact to regulate
      this complex biology is still largely unknown. However, recent technological
      advances, such as chromatin immunoprecipitation (ChIP) paired with massively
      parallel sequencing (ChIP-seq), gene expression profiling, and comprehensive
      bioinformatic analyses, offer new insights into the intricacies of red cell
      molecular circuits.

PMID- 21098098
TI  - Validation of isolated metabolites from drug metabolism studies as analytical
      standards by quantitative NMR.
AB  - In discovery and development, having a qualified metabolite standard is
      advantageous. Chemical synthesis of metabolite standards is often difficult and
      expensive. As an alternative, biological generation and isolation of metabolites
      in the nanomole range are readily feasible. However, without an accurately
      defined concentration, these isolates have limited utility as standards. There is
      a significant history of NMR as both a qualitative and a quantitative technique,
      and these concepts have been merged recently to provide both structural and
      quantitative information on biologically generated isolates from drug metabolism
      studies. Previous methodologies relied on either specialized equipment or the use
      of an internal standard to the isolate. We have developed a technique in which a
      mathematically generated signal can be inserted into a spectrum postacquisition
      and used as a quantitative reference: artificial signal insertion for calculation
      of concentration observed (aSICCO). This technique has several advantages over
      previous methodologies. Any region in the analyte spectra, free from
      interference, can be chosen for the reference signal. In addition, the magnitude
      of the inserted signal can be modified to appropriately match the intensity of
      the sample resonances. Because this is postacquisition quantification, no special
      equipment or pulse sequence is needed. Compared with quantitation via the
      addition of an internal standard (10 mM maleic acid), the signal insertion method
      produced similar results. For each method, precision and accuracy were within +/-
      5%, stability of signal response over 8 days was +/- 5%, and the dynamic range
      was more than 3 orders of magnitude: 10 to 0.01 mM.

PMID- 21098099
TI  - Enhanced virulence of Salmonella enterica serovar typhimurium after passage
      through mice.
AB  - The interaction between Salmonella enterica and the host immune system is
      complex. The outcome of an infection is the result of a balance between the in
      vivo environment where the bacteria survive and grow and the regulation of
      fitness genes at a level sufficient for the bacteria to retain their
      characteristic rate of growth in a given host. Using bacteriological counts from
      tissue homogenates and fluorescence microscopy to determine the spread,
      localization, and distribution of S. enterica in the tissues, we show that,
      during a systemic infection, S. enterica adapts to the in vivo environment. The
      adaptation becomes a measurable phenotype when bacteria that have resided in a
      donor animal are introduced into a recipient naive animal. This adaptation does
      not confer increased resistance to early host killing mechanisms but can be
      detected as an enhancement in the bacterial net growth rate later in the
      infection. The enhanced growth rate is lost upon a single passage in vitro, and
      it is therefore transient and not due to selection of mutants. The adapted
      bacteria on average reach higher intracellular numbers in individual infected
      cells and therefore have patterns of organ spread different from those of
      nonadapted bacteria. These experiments help in developing an understanding of the
      influence of passage in a host on the fitness and virulence of S. enterica.

PMID- 21098100
TI  - Identification of subtilase cytotoxin (SubAB) receptors whose signaling, in
      association with SubAB-induced BiP cleavage, is responsible for apoptosis in HeLa
      cells.
AB  - Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga
      toxigenic Escherichia coli (STEC), causes the 78-kDa glucose-regulated protein
      (GRP78/BiP) cleavage, followed by induction of endoplasmic reticulum (ER) stress,
      leading to caspase-dependent apoptosis via mitochondrial membrane damage by
      Bax/Bak activation. The purpose of the present study was to identify SubAB
      receptors responsible for HeLa cell death. Four proteins, NG2, alpha2beta1
      integrin (ITG), L1 cell adhesion molecule (L1CAM), and hepatocyte growth factor
      receptor (Met), were identified to be SubAB-binding proteins by
      immunoprecipitation and purification, followed by liquid chromatography-tandem
      mass spectrometry analysis. SubAB-induced Bax conformational change, Bax/Bak
      complex formation, caspase activation, and cell death were decreased in beta1
      ITG, NG2, and L1CAM small interfering RNA-transfected cells, but unexpectedly,
      BiP cleavage was still observed. Pretreatment of cells with a function-blocking
      beta1 ITG antibody (monoclonal antibody [MAb] P5D2) enhanced SubAB-induced
      caspase activation; MAb P5D2 alone had no effect on caspase activation.
      Furthermore, we found that SubAB induced focal adhesion kinase fragmentation,
      which was mediated by a proteasome-dependent pathway, and caspase activation was
      suppressed in the presence of proteasome inhibitor. Thus, beta1 ITG serves as a
      SubAB-binding protein and may interact with SubAB-signaling pathways, leading to
      cell death. Our results raise the possibility that although BiP cleavage is
      necessary for SubAB-induced apoptotic cell death, signaling pathways associated
      with functional SubAB receptors may be required for activation of SubAB-dependent
      apoptotic pathways.

PMID- 21098101
TI  - Distinct time-resolved roles for two catabolite-sensing pathways during
      Streptococcus pyogenes infection.
AB  - Many Gram-positive pathogens link the expression of virulence genes to the
      presence of carbon source substrates using overlapping pathways for global
      control of carbon catabolite regulation. However, how these pathways are
      integrated to control the behavior of the transcriptome in time- and compartment
      specific patterns is typically not well understood. In the present study, global
      transcriptome profiling was used to determine the extent to which glucose alters
      gene expression in Streptococcus pyogenes (group A streptococcus) and the
      contributions of the CcpA and LacD.1 catabolite control pathways to the
      regulation of this response in vitro. This analysis revealed that the expression
      of as many as 15% of the genes examined was regulated and that CcpA and LacD.1
      together contribute to the regulation of 60% of this subset. However, numerous
      patterns were observed, including both CcpA- and LacD.1-specific and independent
      regulation, coregulation, and regulation of genes by these pathways independently
      of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most
      coregulated genes. To resolve the roles of these regulators during infection, the
      expression of selected transcripts representative of different regulatory
      patterns was examined in a murine model of soft tissue infection. This revealed
      distinct patterns of misregulation with respect to time in CcpA(-) versus LacD.1(
      ) mutants. Taken together, these data support an important role for carbohydrate
      in the regulation of the transcriptome in tissue and suggest that the CcpA and
      LacD.1 pathways are organized to function at different times during the course of
      an infection.

PMID- 21098102
TI  - Immunization with a ZmpB-based protein vaccine could protect against pneumococcal
      diseases in mice.
AB  - Zinc metalloprotease B (ZmpB) is present in all isolated pneumococcal strains and
      contributes to the pathogenesis of pneumococcal infection. In this study,
      recombinant ZmpB was cloned and expressed in Escherichia coli. The expression of
      ZmpB by different pneumococcal strains was detectable by Western blotting with
      antisera raised to recombinant ZmpB. Flow cytometry analysis demonstrated that
      anti-ZmpB polyclonal antibodies could bind to the cell surface of the
      pneumococcal strains analyzed. Both recombinant ZmpB protein and anti-ZmpB
      polyclonal antibodies significantly inhibited the adhesion of Streptococcus
      pneumoniae D39 to A549 cells. In mouse models, mucosal immunization with
      recombinant ZmpB could significantly reduce pneumococcal lung colonization caused
      by S. pneumoniae serotypes 19F and 14 and significantly increase mice survival
      times following invasive pneumococcal challenge with different pneumococcal
      strains, including serotypes 2, 3, 6B, and 14. Furthermore, intraperitoneal
      immunization with recombinant ZmpB in combination with the recombinant
      pneumolysin mutant (DeltaA146 Ply) and heat shock protein 40 (DnaJ) could enhance
      the protection against pneumococcal infection compared to protection provided by
      single-protein antigens. Passive immunization with hyperimmune antisera against
      these three antigens also demonstrated that the combination of three hyperimmune
      antisera could provide better protection than single antisera. Taken together,
      our results suggest that ZmpB is a good candidate pneumococcal vaccine antigen.

PMID- 21098103
TI  - Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily proteins.
AB  - Clostridium perfringens TpeL belongs to a family of large clostridial cytotoxins
      that encompasses Clostridium difficile toxin A (TcdA) and B (TcdB) and
      Clostridium sordellii lethal toxin (TcsL). We report here the identification of
      the TpeL-catalyzed modification of small GTPases. A recombinant protein (TpeL1
      525) derived from the TpeL N-terminal catalytic domain in the presence of
      streptolysin O (SLO) induced the rounding of Vero cells and the glycosylation of
      cellular Rac1. Among several hexoses tested, UDP-N-acetyl-glucosamine (UDP
      GlcNAc) and UDP-glucose (UDP-Glc) served as cosubstrates for TpeL1-525-catalyzed
      modifications. TpeL1-525 catalyzed the incorporation of UDP-Glc into Ha-Ras,
      Rap1B, and RalA and of UDP-GlcNAc into Rac1, Ha-Ras, Rap1B, and RalA. In Rac1,
      TpeL and TcdB share the same acceptor amino acid for glycosylation, Thr-35. In
      Vero cells treated with TpeL1-525 in the presence of SLO, glycosylation leads to
      a translocation of the majority of Rac1 and Ha-Ras to the membrane. We
      demonstrate for first time that TpeL uses both UDP-GlcNAc and UDP-Glc as donor
      cosubstrates and modifies the Rac1 and Ras subfamily by glycosylation to mediate
      its cytotoxic effects.

PMID- 21098104
TI  - The Vi capsular polysaccharide prevents complement receptor 3-mediated clearance
      of Salmonella enterica serotype Typhi.
AB  - Capsular polysaccharides are important virulence factors of invasive bacterial
      pathogens. Here we studied the role of the virulence (Vi) capsular polysaccharide
      of Salmonella enterica serotype Typhi (S. Typhi) in preventing innate immune
      recognition by complement. Comparison of capsulated S. Typhi with a noncapsulated
      mutant (DeltatviBCDE vexABCDE mutant) revealed that the Vi capsule interfered
      with complement component 3 (C3) deposition. Decreased complement fixation
      resulted in reduced bacterial binding to complement receptor 3 (CR3) on the
      surface of murine macrophages in vitro and decreased CR3-dependent clearance of
      Vi capsulated S. Typhi from the livers and spleens of mice. Opsonization of
      bacteria with immune serum prior to intraperitoneal infection increased clearance
      of capsulated S. Typhi from the liver. Our data suggest that the Vi capsule
      prevents CR3-dependent clearance, which can be overcome in part by a specific
      antibody response.

PMID- 21098105
TI  - Identification of gene products involved in the oxidative stress response of
      Moraxella catarrhalis.
AB  - Moraxella catarrhalis is subjected to oxidative stress from both internal and
      environmental sources. A previous study (C. D. Pericone, K. Overweg, P. W.
      Hermans, and J. N. Weiser, Infect. Immun. 68:3990-3997, 2000) indicated that a
      wild-type strain of M. catarrhalis was very resistant to killing by exogenous
      hydrogen peroxide (H2O2). The gene encoding OxyR, a LysR family transcriptional
      regulator, was identified and inactivated in M. catarrhalis strain O35E,
      resulting in an increase in sensitivity to killing by H2O2 in disk diffusion
      assays and a concomitant aerobic serial dilution effect. Genes encoding a
      predicted catalase (KatA) and an alkyl hydroperoxidase (AhpCF) showed dose
      dependent upregulation in wild-type cells exposed to H2O2. DNA microarray and
      real-time reverse transcription-PCR (RT-PCR) analyses identified M. catarrhalis
      genes whose expression was affected by oxidative stress in an OxyR-dependent
      manner. Testing of M. catarrhalis O35E katA and ahpC mutants for their abilities
      to scavenge exogenous H2O2 showed that the KatA catalase was responsible for most
      of this activity in the wild-type parent strain. The introduction of the same
      mutations into M. catarrhalis strain ETSU-4 showed that the growth of a ETSU-4
      katA mutant was markedly inhibited by the addition of 50 mM H2O2 but that this
      mutant could still form a biofilm equivalent to that produced by its wild-type
      parent strain.

PMID- 21098106
TI  - The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential
      function of Sting in the in vivo interferon response to Listeria monocytogenes
      and cyclic dinucleotides.
AB  - Type I interferons (IFNs) are central regulators of the innate and adaptive
      immune responses to viral and bacterial infections. Type I IFNs are induced upon
      cytosolic detection of microbial nucleic acids, including DNA, RNA, and the
      bacterial second messenger cyclic-di-GMP (c-di-GMP). In addition, a recent study
      demonstrated that the intracellular bacterial pathogen Listeria monocytogenes
      stimulates a type I IFN response due to cytosolic detection of bacterially
      secreted c-di-AMP. The transmembrane signaling adaptor Sting (Tmem173, Mita,
      Mpys, Eris) has recently been implicated in the induction of type I IFNs in
      response to cytosolic DNA and/or RNA. However, the role of Sting in response to
      purified cyclic dinucleotides or during in vivo L. monocytogenes infection has
      not been addressed. In order to identify genes important in the innate immune
      response, we have been conducting a forward genetic mutagenesis screen in C57BL/6
      mice using the mutagen N-ethyl-N-nitrosourea (ENU). Here we describe a novel
      mutant mouse strain, Goldenticket (Gt), that fails to produce type I IFNs upon L.
      monocytogenes infection. By genetic mapping and complementation experiments, we
      found that Gt mice harbor a single nucleotide variant (T596A) of Sting that
      functions as a null allele and fails to produce detectable protein. Analysis of
      macrophages isolated from Gt mice revealed that Sting is absolutely required for
      the type I interferon response to both c-di-GMP and c-di-AMP. Additionally, Sting
      is required for the response to c-di-GMP and L. monocytogenes in vivo. Our
      results provide new functions for Sting in the innate interferon response to
      pathogens.

PMID- 21098107
TI  - Adsorption of components of the plasma kinin-forming system on the surface of
      Porphyromonas gingivalis involves gingipains as the major docking platforms.
AB  - Enhanced production of proinflammatory bradykinin-related peptides, the kinins,
      has been suggested to contribute to the pathogenesis of periodontitis, a common
      inflammatory disease of human gingival tissues. In this report, we describe a
      plausible mechanism of activation of the kinin-generating system, also known as
      the contact system or kininogen-kallikrein-kinin system, by the adsorption of its
      plasma-derived components such as high-molecular-mass kininogen (HK),
      prekallikrein (PK), and Hageman factor (FXII) to the cell surface of periodontal
      pathogen Porphyromonas gingivalis. The adsorption characteristics of mutant
      strains deficient in selected proteins of the cell envelope suggested that the
      surface-associated cysteine proteinases, gingipains, bearing
      hemagglutinin/adhesin domains (RgpA and Kgp) serve as the major platforms for HK
      and FXII adhesion. These interactions were confirmed by direct binding tests
      using microplate-immobilized gingipains and biotinylated contact factors. Other
      bacterial cell surface components such as fimbriae and lipopolysaccharide were
      also found to contribute to the binding of contact factors, particularly PK.
      Analysis of kinin release in plasma upon contact with P. gingivalis showed that
      the bacterial surface-dependent mechanism is complementary to the previously
      described kinin generation system dependent on HK and PK proteolytic activation
      by the gingipains. We also found that several P. gingivalis clinical isolates
      differed in the relative significance of these two mechanisms of kinin
      production. Taken together, these data show the importance of this specific type
      of bacterial surface-host homeostatic system interaction in periodontal
      infections.

PMID- 21098108
TI  - NALP1 influences susceptibility to human congenital toxoplasmosis,
      proinflammatory cytokine response, and fate of Toxoplasma gondii-infected
      monocytic cells.
AB  - NALP1 is a member of the NOD-like receptor (NLR) family of proteins that form
      inflammasomes. Upon cellular infection or stress, inflammasomes are activated,
      triggering maturation of proinflammatory cytokines and downstream cellular
      signaling mediated through the MyD88 adaptor. Toxoplasma gondii is an obligate
      intracellular parasite that stimulates production of high levels of
      proinflammatory cytokines that are important in innate immunity. In this study,
      susceptibility alleles for human congenital toxoplasmosis were identified in the
      NALP1 gene. To investigate the role of the NALP1 inflammasome during infection
      with T. gondii, we genetically engineered a human monocytic cell line for NALP1
      gene knockdown by RNA interference. NALP1 silencing attenuated progression of T.
      gondii infection, with accelerated host cell death and eventual cell
      disintegration. In line with this observation, upregulation of the
      proinflammatory cytokines interleukin-1beta (IL-1beta), IL-18, and IL-12 upon T.
      gondii infection was not observed in monocytic cells with NALP1 knockdown. These
      findings suggest that the NALP1 inflammasome is critical for mediating innate
      immune responses to T. gondii infection and pathogenesis. Although there have
      been recent advances in understanding the potent activity of inflammasomes in
      directing innate immune responses to disease, this is the first report, to our
      knowledge, on the crucial role of the NALP1 inflammasome in the pathogenesis of
      T. gondii infections in humans.

PMID- 21098109
TI  - Photic EEG-driving responses related to ictal phases and trigger sensitivity in
      migraine: a longitudinal, controlled study.
AB  - INTRODUCTION: Photic driving is believed to be increased in migraineurs and has
      been interpreted as a sign of cortical hyperexcitability. However, most previous
      studies have included patients in various phases of the migraine cycle. The
      results are, therefore, difficult to interpret as neurophysiological
      abnormalities tend to accumulate close to the attack in migraineurs. SUBJECTS AND
      METHODS: We recorded steady state visual evoked EEG-responses (SSVEPs) for 6, 12,
      18 and 24 Hz flash stimuli from 33 migraineurs without aura, eight migraineurs
      with aura and 32 healthy controls. Interictal recordings were compared pair-wise
      with recordings before, during and after attack, as well as with EEGs from
      healthy controls. Driving power was also correlated with sensory hypersensitivity
      and severity of migraine. RESULTS: Between attacks, driving responses to 18 Hz
      and 24 Hz were attenuated in migraineurs without aura. Driving power of 12 Hz
      increased before the attack. Attack trigger sensitivity, photophobia, pain
      intensity and a family history of migraine were related to decreased and/or
      symmetric photic driving. CONCLUSIONS: Earlier results may have overestimated the
      driving response in migraine due to inclusion of recordings during the preictal
      interval and/or habituation among controls. Abnormal photic driving may be
      related to the pathophysiology of clinical sensory hypersensitivity.

PMID- 21098110
TI  - OnabotulinumtoxinA for the treatment of chronic migraine not quite there. . .

PMID- 21098111
TI  - Phosphorylated Rad18 directs DNA polymerase eta to sites of stalled replication.
AB  - The E3 ubiquitin ligase Rad18 guides DNA Polymerase eta (Poleta) to sites of
      replication fork stalling and mono-ubiquitinates proliferating cell nuclear
      antigen (PCNA) to facilitate binding of Y family trans-lesion synthesis (TLS) DNA
      polymerases during TLS. However, it is unclear exactly how Rad18 is regulated in
      response to DNA damage and how Rad18 activity is coordinated with progression
      through different phases of the cell cycle. Here we identify Rad18 as a novel
      substrate of the essential protein kinase Cdc7 (also termed Dbf4/Drf1-dependent
      Cdc7 kinase [DDK]). A serine cluster in the Poleta-binding motif of Rad 18 is
      phosphorylated by DDK. Efficient association of Rad18 with Poleta is dependent on
      DDK and is necessary for redistribution of Poleta to sites of replication fork
      stalling. This is the first demonstration of Rad18 regulation by direct
      phosphorylation and provides a novel mechanism for integration of S phase
      progression with postreplication DNA repair to maintain genome stability.

PMID- 21098112
TI  - The RSC chromatin-remodeling complex influences mitotic exit and adaptation to
      the spindle assembly checkpoint by controlling the Cdc14 phosphatase.
AB  - Upon prolonged activation of the spindle assembly checkpoint, cells escape from
      mitosis through a mechanism called adaptation or mitotic slippage, which is
      thought to underlie the resistance of cancer cells to antimitotic drugs. We show
      that, in budding yeast, this mechanism depends on known essential and
      nonessential regulators of mitotic exit, such as the Cdc14 early anaphase release
      (FEAR) pathway for the release of the Cdc14 phosphatase from the nucleolus in
      early anaphase. Moreover, the RSC (remodel the structure of chromatin) chromatin
      remodeling complex bound to its accessory subunit Rsc2 is involved in this
      process as a novel component of the FEAR pathway. We show that Rsc2 interacts
      physically with the polo kinase Cdc5 and is required for timely phosphorylation
      of the Cdc14 inhibitor Net1, which is important to free Cdc14 in the active form.
      Our data suggest that fine-tuning regulators of mitotic exit have important
      functions during mitotic progression in cells treated with microtubule poisons
      and might be promising targets for cancer treatment.

PMID- 21098113
TI  - Drosophila Boi limits Hedgehog levels to suppress follicle stem cell
      proliferation.
AB  - Stem cells depend on signals from cells within their microenvironment, or niche,
      as well as factors secreted by distant cells to regulate their maintenance and
      function. Here we show that Boi, a Hedgehog (Hh)-binding protein, is a novel
      suppressor of proliferation of follicle stem cells (FSCs) in the Drosophila
      ovary. Hh is expressed in apical cells, distant from the FSC niche, and diffuses
      to reach FSCs, where it promotes FSC proliferation. We show that Boi is expressed
      in apical cells and exerts its suppressive effect on FSC proliferation by binding
      to and sequestering Hh on the apical cell surface, thereby inhibiting Hh
      diffusion. Our studies demonstrate that cells distant from the local niche can
      regulate stem cell function through ligand sequestration, a mechanism that likely
      is conserved in other epithelial tissues.

PMID- 21098114
TI  - Robust control of mitotic spindle orientation in the developing epidermis.
AB  - Progenitor cells must balance self-amplification and production of differentiated
      progeny during development and homeostasis. In the epidermis, progenitors divide
      symmetrically to increase surface area and asymmetrically to promote
      stratification. In this study, we show that individual epidermal cells can
      undergo both types of division, and therefore, the balance is provided by the sum
      of individual cells' choices. In addition, we define two control points for
      determining a cell's mode of division. First is the expression of the mouse
      Inscuteable gene, which is sufficient to drive asymmetric cell division (ACD).
      However, there is robust control of division orientation as excessive ACDs are
      prevented by a change in the localization of NuMA, an effector of spindle
      orientation. Finally, we show that p63, a transcriptional regulator of
      stratification, does not control either of these processes. These data have
      uncovered two important regulatory points controlling ACD in the epidermis and
      allow a framework for analysis of how external cues control this important
      choice.

PMID- 21098115
TI  - An invasive podosome-like structure promotes fusion pore formation during
      myoblast fusion.
AB  - Recent studies in Drosophila have implicated actin cytoskeletal remodeling in
      myoblast fusion, but the cellular mechanisms underlying this process remain
      poorly understood. Here we show that actin polymerization occurs in an asymmetric
      and cell type-specific manner between a muscle founder cell and a fusion
      competent myoblast (FCM). In the FCM, a dense F-actin-enriched focus forms at the
      site of fusion, whereas a thin sheath of F-actin is induced along the apposing
      founder cell membrane. The FCM-specific actin focus invades the apposing founder
      cell with multiple finger-like protrusions, leading to the formation of a single
      channel macro fusion pore between the two muscle cells. Two actin nucleation
      promoting factors of the Arp2/3 complex, WASP and Scar, are required for the
      formation of the F-actin foci, whereas WASP but not Scar promotes efficient foci
      invasion. Our studies uncover a novel invasive podosome-like structure (PLS) in a
      developing tissue and reveal a previously unrecognized function of PLSs in
      facilitating cell membrane juxtaposition and fusion.

PMID- 21098117
TI  - Ted Salmon: kinetochores at the core of it all. Interview by Caitlin Sedwick.

PMID- 21098116
TI  - Defects in nuclear pore assembly lead to activation of an Aurora B-mediated
      abscission checkpoint.
AB  - Correct assembly of nuclear pore complexes (NPCs), which directly and indirectly
      control nuclear environment and architecture, is vital to genomic regulation. We
      previously found that nucleoporin 153 (Nup 153) is required for timely
      progression through late mitosis. In this study, we report that disruption of Nup
      153 function by either small interfering RNA-mediated depletion or expression of
      a dominant-interfering Nup 153 fragment results in dramatic mistargeting of the
      pore basket components Tpr and Nup 50 in midbody-stage cells. We find a
      concomitant appearance of aberrantly localized active Aurora B and an Aurora B
      dependent delay in abscission. Depletion of Nup 50 is also sufficient to increase
      the number of midbody-stage cells and, likewise, triggers distinctive
      mislocalization of Aurora B. Together, our results suggest that defects in
      nuclear pore assembly, and specifically the basket structure, at this time of the
      cell cycle activate an Aurora B-mediated abscission checkpoint, thereby ensuring
      that daughter cells are generated only when fully formed NPCs are present.

PMID- 21098118
TI  - Distinguishing the roles of Topoisomerases I and II in relief of transcription
      induced torsional stress in yeast rRNA genes.
AB  - To better understand the role of topoisomerase activity in relieving
      transcription-induced supercoiling, yeast genes encoding rRNA were visualized in
      cells deficient for either or both of the two major topoisomerases. In the
      absence of both topoisomerase I (Top1) and topoisomerase II (Top2) activity,
      processivity was severely impaired and polymerases were unable to transcribe
      through the 6.7-kb gene. Loss of Top1 resulted in increased negative superhelical
      density (two to six times the normal value) in a significant subset of rRNA
      genes, as manifested by regions of DNA template melting. The observed DNA bubbles
      were not R-loops and did not block polymerase movement, since genes with DNA
      template melting showed no evidence of slowed elongation. Inactivation of Top2,
      however, resulted in characteristic signs of slowed elongation in rRNA genes,
      suggesting that Top2 alleviates transcription-induced positive supercoiling.
      Together, the data indicate that torsion in front of and behind transcribing
      polymerase I has different consequences and different resolution. Positive
      torsion in front of the polymerase induces supercoiling (writhe) and is largely
      resolved by Top2. Negative torsion behind the polymerase induces DNA strand
      separation and is largely resolved by Top1.

PMID- 21098119
TI  - SCFCdc4 enables mating type switching in yeast by cyclin-dependent kinase
      mediated elimination of the Ash1 transcriptional repressor.
AB  - In the budding yeast Saccharomyces cerevisiae, mother cells switch mating types
      between a and alpha forms, whereas daughter cells do not. This developmental
      asymmetry arises because the expression of the HO endonuclease, which initiates
      the interconversion of a and alpha mating type cassettes, is extinguished by the
      daughter-specific Ash1 transcriptional repressor. When daughters become mothers
      in the subsequent cell cycle, Ash1 must be eliminated to enable a new
      developmental state. Here, we report that the ubiquitin ligase SCF(Cdc4) mediates
      the phosphorylation-dependent elimination of Ash1. The inactivation of SCF(Cdc4)
      stabilizes Ash1 in vivo, and consistently, Ash1 binds to and is ubiquitinated by
      SCF(Cdc4) in a phosphorylation-dependent manner in vitro. The mutation of a
      critical in vivo cyclin-dependent kinase (CDK) phosphorylation site (Thr290) on
      Ash1 reduces its ubiquitination and rate of degradation in vivo and decreases the
      frequency of mating type switching. Ash1 associates with active Cdc28 kinase in
      vivo and is targeted to SCF(Cdc4) in a Cdc28-dependent fashion in vivo and in
      vitro. Ash1 recognition by Cdc4 appears to be mediated by at least three
      phosphorylation sites that form two redundant diphosphorylated degrons. The
      phosphorylation-dependent elimination of Ash1 by the ubiquitin-proteasome system
      thus underpins developmental asymmetry in budding yeast.

PMID- 21098120
TI  - La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein
      MLLE domain via a variant PAM2w motif, and can promote mRNA stability.
AB  - The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA
      ligands and stabilizes them against 3'-end-mediated decay. We report that newly
      described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and
      interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and
      reciprocal immunoprecipitations (IPs) from HeLa cells revealed that LARP4
      interacts with RACK1, a 40S ribosome- and mRNA-associated protein. LARP4
      cosediments with 40S ribosome subunits and polyribosomes, and its knockdown
      decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs
      decrease LARP4 association with polysomes. Several translation and mRNA
      metabolism-related proteins use a PAM2 sequence containing a critical invariant
      phenylalanine to make direct contact with the MLLE domain of PABP, and their
      competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all ~150
      previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 (PAM2w) with
      tryptophan in place of the phenylalanine. Binding and nuclear magnetic resonance
      (NMR) studies have shown that a peptide representing LARP4 PAM2w interacts with
      the MLLE of PABP within the affinity range measured for other PAM2 motif
      peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket
      in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4
      expression stimulates luciferase reporter activity by promoting mRNA stability,
      as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that
      LARP4 activity is integrated with other PAM2 protein activities by PABP as part
      of mRNA homeostasis.

PMID- 21098121
TI  - Fission yeast Pot1 and RecQ helicase are required for efficient chromosome
      segregation.
AB  - Pot1 is a single-stranded telomere-binding protein that is conserved from fission
      yeast to mammals. Deletion of Schizosaccharomyces pombe pot1(+) causes immediate
      telomere loss. S. pombe Rqh1 is a homolog of the human RecQ helicase WRN, which
      plays essential roles in the maintenance of genomic stability. Here, we
      demonstrate that a pot1Delta rqh1-hd (helicase-dead) double mutant maintains
      telomeres that are dependent on Rad51-mediated homologous recombination.
      Interestingly, the pot1Delta rqh1-hd double mutant displays a "cut" (cell
      untimely torn) phenotype and is sensitive to the antimicrotubule drug
      thiabendazole (TBZ). Moreover, the chromosome ends of the double mutant do not
      enter the pulsed-field electrophoresis gel. These results suggest that the
      entangled chromosome ends in the pot1Delta rqh1-hd double mutant inhibit
      chromosome segregation, signifying that Pot1 and Rqh1 are required for efficient
      chromosome segregation. We also found that POT1 knockdown, WRN-deficient human
      cells are sensitive to the antimicrotubule drug vinblastine, implying that some
      of the functions of S. pombe Pot1 and Rqh1 may be conserved in their respective
      human counterparts POT1 and WRN.

PMID- 21098122
TI  - Mre11 nuclease activity and Ctp1 regulate Chk1 activation by Rad3ATR and Tel1ATM
      checkpoint kinases at double-strand breaks.
AB  - Rad3, the Schizosaccharomyces pombe ortholog of human ATR and Saccharomyces
      cerevisiae Mec1, activates the checkpoint kinase Chk1 in response to DNA double
      strand breaks (DSBs). Rad3(ATR/Mec1) associates with replication protein A (RPA),
      which binds single-stranded DNA overhangs formed by DSB resection. In humans and
      both yeasts, DSBs are initially detected and processed by the Mre11-Rad50
      Nbs1(Xrs2) (MRN) nucleolytic protein complex in association with the Tel1(ATM)
      checkpoint kinase and the Ctp1(CtIP/Sae2) DNA-end processing factor; however, in
      budding yeast, neither Mre11 nuclease activity or Sae2 are required for Mec1
      signaling at irreparable DSBs. Here, we investigate the relationship between DNA
      end processing and the DSB checkpoint response in fission yeast, and we report
      that Mre11 nuclease activity and Ctp1 are critical for efficient Rad3-to-Chk1
      signaling. Moreover, deleting Ctp1 reveals a Tel1-to-Chk1 signaling pathway that
      bypasses Rad3. This pathway requires Mre11 nuclease activity, the Rad9-Hus1-Rad1
      (9-1-1) checkpoint clamp complex, and Crb2 checkpoint mediator. Ctp1 negatively
      regulates this pathway by controlling MRN residency at DSBs. A Tel1-to-Chk1
      checkpoint pathway acting at unresected DSBs provides a mechanism for coupling
      Chk1 activation to the initial detection of DSBs and suggests that ATM may
      activate Chk1 by both direct and indirect mechanisms in mammalian cells.

PMID- 21098126
TI  - The essentiality of the epididymal fat pad for spermatogenesis.

PMID- 21098123
TI  - Control of chromatin structure by spt6: different consequences in coding and
      regulatory regions.
AB  - Spt6 is a highly conserved factor required for normal transcription and chromatin
      structure. To gain new insights into the roles of Spt6, we measured nucleosome
      occupancy along Saccharomyces cerevisiae chromosome III in an spt6 mutant. We
      found that the level of nucleosomes is greatly reduced across some, but not all,
      coding regions in an spt6 mutant, with nucleosome loss preferentially occurring
      over highly transcribed genes. This result provides strong support for recent
      studies that have suggested that transcription at low levels does not displace
      nucleosomes, while transcription at high levels does, and adds the idea that Spt6
      is required for restoration of nucleosomes at the highly transcribed genes.
      Unexpectedly, our studies have also suggested that the spt6 effects on nucleosome
      levels across coding regions do not cause the spt6 effects on mRNA levels,
      suggesting that the role of Spt6 across coding regions is separate from its role
      in transcriptional regulation. In the case of the CHA1 gene, regulation by Spt6
      likely occurs by controlling the position of the +1 nucleosome. These results,
      along with previous studies, suggest that Spt6 regulates transcription by
      controlling chromatin structure over regulatory regions, and its effects on
      nucleosome levels over coding regions likely serve an independent function.

PMID- 21098127
TI  - Tuberoinfundibular peptide of 39 residues (TIP39): a new player in the
      translation of sensory input to prolactin release during lactation.

PMID- 21098128
TI  - Epistle.

PMID- 21098124
TI  - The essential function for serum response factor in T-cell development reflects
      its specific coupling to extracellular signal-regulated kinase signaling.
AB  - Serum response factor (SRF) recruits members of two families of signal-regulated
      coactivators, the extracellular signal-regulated kinase (ERK)-regulated ternary
      complex factors (TCFs) and the actin-regulated myocardin-related transcription
      factors (MRTFs), to its target genes through its DNA-binding domain. Whether
      coactivator association is required for SRF function in vivo and whether
      particular SRF functions reflect specific coupling to one or the other signal
      pathway have remained largely unexplored. We show that SRF is essential for
      thymocyte positive selection and thymic T(reg) and NK T-cell development but
      dispensable for early thymocyte development and negative selection. Expression of
      wild-type SRF, or mutants lacking the N-terminal phosphorylation sites or C
      terminal transcriptional activation domain, restores positive selection in SRF
      null thymocytes. In contrast, SRF.V194E, which cannot recruit TCF or MRTF family
      members, is inactive, although it is recruited to target genes. Fusion of a TCF C
      terminal activation domain to SRF.V194E effectively restores ERK-dependent single
      positive (SP) thymocyte development. The resulting SP thymocytes exhibit normal
      surface marker expression and proliferation following T-cell receptor cross
      linking. Thus, ERK signaling through the TCF pathway to SRF is necessary and
      sufficient for SRF function in thymocyte positive selection.

PMID- 21098130
TI  - Benzodiazepines for prolonged seizures.

PMID- 21098132
TI  - Sleep, snoring and acute life-threatening events.

PMID- 21098134
TI  - Do you know your lobes?

PMID- 21098137
TI  - Detection and elimination of interference by the heterophilic antibody in
      antibody microarray-based immunoassay.

PMID- 21098138
TI  - Therapeutic approaches to target inflammation in type 2 diabetes.
AB  - BACKGROUND: Chronic inflammation may participate in the pathogenesis of insulin
      resistance, type 2 diabetes, and cardiovascular disease and may be a common
      denominator that links obesity to these disease states. CONTENT: Epidemiologic
      studies have linked inflammatory biomarkers to incident diabetes and
      cardiovascular disease risk. Cellular and animal studies have provided support to
      the idea that inflammation mediates these disease processes, providing impetus to
      pharmacologically target these pathways for disease treatment and prevention. We
      review clinical strategies to target inflammation, with a focus on the
      antiinflammatory and antihyperglycemic effects of salicylates. SUMMARY: The
      evolving concept of diet-induced obesity driving insulin resistance, type 2
      diabetes, and cardiovascular disease through immunologic processes provides new
      opportunities for the use of antiinflammatory strategies to correct the metabolic
      consequences of excess adiposity.

PMID- 21098139
TI  - Heuristic RNA pseudoknot prediction including intramolecular kissing hairpins.
AB  - Pseudoknots are an essential feature of RNA tertiary structures. Simple H-type
      pseudoknots have been studied extensively in terms of biological functions,
      computational prediction, and energy models. Intramolecular kissing hairpins are
      a more complex and biologically important type of pseudoknot in which two hairpin
      loops form base pairs. They are hard to predict using free energy minimization
      due to high computational requirements. Heuristic methods that allow arbitrary
      pseudoknots strongly depend on the quality of energy parameters, which are not
      yet available for complex pseudoknots. We present an extension of the heuristic
      pseudoknot prediction algorithm DotKnot, which covers H-type pseudoknots and
      intramolecular kissing hairpins. Our framework allows for easy integration of
      advanced H-type pseudoknot energy models. For a test set of RNA sequences
      containing kissing hairpins and other types of pseudoknot structures, DotKnot
      outperforms competing methods from the literature. DotKnot is available as a web
      server under http://dotknot.csse.uwa.edu.au.

PMID- 21098140
TI  - DEAH-box ATPase Prp16 has dual roles in remodeling of the spliceosome in
      catalytic steps.
AB  - The assembly of the spliceosome involves dynamic rearrangements of interactions
      between snRNAs, protein components, and the pre-mRNA substrate. DExD/H-box
      ATPases are required to mediate structural changes of the spliceosome, utilizing
      the energy of ATP hydrolysis. Two DExD/H-box ATPases are required for the
      catalytic steps of the splicing pathway, Prp2 for the first step and Prp16 for
      the second step, both belonging to the DEAH subgroup of the protein family. The
      detailed mechanism of their action was not well understood until recently, when
      Prp2 was shown to be required for the release of U2 components SF3a and SF3b,
      presumably to allow the binding of Cwc25 to promote the first transesterification
      reaction. We show here that Cwc25 and Yju2 are released after the reaction in
      Prp16- and ATP-dependent manners, possibly to allow for the binding of Prp22,
      Prp18, and Slu7 to promote the second catalytic reaction. The binding of Cwc25 to
      the spliceosome is destabilized by mutations at the branchpoint sequence,
      suggesting that Cwc25 may bind to the branch site. We also show that Prp16 has an
      ATP-independent role in the first catalytic step, in addition to its known role
      in the second step. In the absence of ATP, Prp16 stabilizes the binding of Cwc25
      to the spliceosome formed with branchpoint mutated pre-mRNAs to facilitate their
      splicing. Our results uncovered novel functions of Prp16 in both catalytic steps,
      and provide mechanistic insights into splicing catalysis.

PMID- 21098141
TI  - Cellular stress induces cytoplasmic RNA granules in fission yeast.
AB  - Severe stress causes plant and animal cells to form large cytoplasmic granules
      containing RNA and proteins. Here, we demonstrate the existence of stress-induced
      cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known
      protein components of mammalian processing bodies and stress granules are found
      in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding
      protein (Pabp) colocalizes in stress-induced granules with decapping protein.
      After glucose deprivation, protein kinase A (PKA) is required for accumulation of
      Pabp-positive granules and translational down-regulation. This is the first
      demonstration of a role for PKA in RNA granule formation. In mammals, the
      translation initiation protein eIF2alpha is a key regulator of formation of
      granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable
      eIF2alpha does not block but delays granule formation and subsequent clearance
      after exposure to hyperosmosis. At least two separate pathways in S. pombe appear
      to regulate stress-induced granules: pka1 mutants are fully proficient to form
      granules after hyperosmotic shock; conversely, eIF2alpha does not affect granule
      formation in glucose starvation. Further, we demonstrate a Pka1-dependent link
      between calcium perturbation and RNA granules, which has not been described
      earlier in any organism.

PMID- 21098142
TI  - Quantitative approaches to monitor protein-nucleic acid interactions using
      fluorescent probes.
AB  - Sequence-specific recognition of nucleic acids by proteins is required for nearly
      every aspect of gene expression. Quantitative binding experiments are a useful
      tool to measure the ability of a protein to distinguish between multiple
      sequences. Here, we describe the use of fluorophore-labeled oligonucleotide
      probes to quantitatively monitor protein/nucleic acid interactions. We review two
      complementary experimental methods, fluorescence polarization and fluorescence
      electrophoretic mobility shift assays, that enable the quantitative measurement
      of binding affinity. We also present two strategies for post-synthetic end
      labeling of DNA or RNA oligonucleotides with fluorescent dyes. The approaches
      discussed here are efficient and sensitive, providing a safe and accessible
      alternative to the more commonly used radio-isotopic methods.

PMID- 21098143
TI  - Pharmacokinetic interaction between zolpidem and carbamazepine in healthy
      volunteers.
AB  - The objective of this study was to evaluate the pharmacokinetic interaction
      between zolpidem and carbamazepine in healthy volunteers. The study consisted of
      2 periods: period 1 (reference), when each volunteer received a single dose of 5
      mg zolpidem, and period 2 (test), when each volunteer received a single dose of 5
      mg zolpidem and 400 mg carbamazepine. Between the 2 periods, the participants
      were treated for 15 days with a single daily dose of 400 mg carbamazepine.
      Pharmacokinetic parameters of zolpidem administered in each treatment period were
      calculated using noncompartmental analysis. In the 2 periods of treatments, the
      mean peak plasma concentrations (C(max)) were 59 ng/mL (zolpidem alone) and 35
      ng/mL (zolpidem after pretreatment with carbamazepine). The t(max), times taken
      to reach C(max), were 0.9 hours and 1.0 hour, respectively, and the total areas
      under the curve (AUC(0-infinity)) were 234.9 ng.h/mL and 101.5 ng.h/mL,
      respectively. The half-life of zolpidem was 2.3 and 1.6 hours, respectively.
      Carbamazepine interacts with zolpidem in healthy volunteers and lowers its
      bioavailability by about 57%. The experimental data demonstrate the
      pharmacokinetic interaction between zolpidem and carbamazepine and suggest that
      the observed interaction may be clinically significant, but its relevance has to
      be confirmed.

PMID- 21098145
TI  - Complementary and alternative medicine use among people with diabetes in Turkey.
AB  - The aim of this study was to investigate use of complementary and alternative
      medicines, and factors that affect use of these agents, in individuals with
      diabetes. This cross-sectional and descriptive study was performed at the
      outpatient clinics of four hospitals in Turkey with 396 diabetic individuals
      between October 2006 and March 2007. In this study, 34.6% of the participants
      were using complementary and alternative medicine in addition to conventional
      medicine; 73% of these individuals had not informed their doctors and nurses
      about their complementary and alternative medicine practice. Nurses, as health
      care providers, should not ignore complementary and alternative medicine options.
      Instead, they should try to determine the rate of complementary and alternative
      medicine use among their patients and understand their effects and the reasons
      for use of these agents. Nurses should learn more about these medicines and
      educate their patients.

PMID- 21098146
TI  - Outcomes of interventions for Alzheimer's family caregivers in Mexico.
AB  - The study examines which of three interventions of cognitive conduct, laughter,
      or a mixed intervention including both cognitive conduct and laughter components,
      is more effective for improvement of attitudes toward care and reduction of
      anxiety among female Mexican caregivers of family members with Alzheimer's
      disease. A repeated measures quasi-experimental design with four groups, three
      experimental and a control group, was used. All intervention groups received
      cognitive conduct, laughter, or a mixed intervention weekly for 8 weeks. The
      control group received information about home accident prevention. Outcome
      measurements were performed at baseline, Week 4, end of the intervention (Week
      8), and 4 weeks following the intervention completion. A repeated measures ANOVA
      was used for each outcome variable and the Tukey's post hoc analysis to determine
      group differences. Results suggest that the cognitive conduct component
      significantly improved positive attitudes toward care and reduced anxiety both at
      the end of the intervention and at follow-up.

PMID- 21098147
TI  - Left vocal cord paralysis after extreme preterm birth, a new clinical scenario in
      adults.
AB  - OBJECTIVE: The goal was to study the incidence and long-term consequences of left
      vocal cord paralysis (LVCP) after neonatal surgical treatment of patent ductus
      arteriosus (PDA) in a population-based cohort of adults who were born at
      gestational ages of <=28 weeks or with birth weights of <=1000 g in western
      Norway. METHODS: Subjects with a history of neonatal PDA surgery were examined
      with transnasal flexible laryngoscopy, and those with LVCP were examined with
      continuous laryngoscopy during maximal treadmill exercise (continuous
      laryngoscopy exercise testing). All subjects underwent lung function testing,
      ergospirometry, and pulmonary high-resolution computed tomography. Symptoms were
      recorded with a questionnaire. RESULTS: Forty-four (86%) of 51 eligible preterm
      infants participated in the study, 13 (26%) had a history of PDA surgery and 7
      (54%) had LVCP, with the laryngeal appearances varying slightly. As a group,
      subjects with LVCP had significant airway obstruction, no decreases in aerobic
      capacity, and no obvious evidence of longstanding aspiration on high-resolution
      computed tomography scans. The continuous laryngoscopy exercise tests revealed
      increasing respiratory symptoms in parallel with increasing anteromedial collapse
      of the left aryepiglottic folds as the exercise load increased. Hoarseness and
      voice-related symptoms were the most typical complaints. Symptoms were attributed
      erroneously to other diseases for at least 2 subjects. CONCLUSIONS: LVCP is not
      uncommon in young adults exposed to PDA surgery as preterm infants. The condition
      may be overlooked easily, and symptoms may be confused with those of other
      diseases. Laryngoscopy should be offered on the basis of liberal indications
      after PDA ligation.

PMID- 21098148
TI  - Adolescents' needs for health care privacy.
AB  - OBJECTIVE: To understand adolescents' preferences for multidimensional aspects of
      privacy, including psychological, social, and physical, and confidentiality
      (informational privacy) in the health care setting. PATIENTS AND METHODS: Fifty
      four adolescents with and without chronic illness participated in 12 focus groups
      composed of participants of the same age (11-14 or 15-19 years), gender, and
      health status. Health care preferences, including privacy and confidentiality,
      were discussed, and themes were determined. On the basis of a literature review,
      Burgoon's framework best represented participant feedback. The data were
      categorized as representations of informational, psychological, social, or
      physical privacy. RESULTS: Maintaining informational privacy (ie, keeping
      information confidential) was most salient to the adolescents. Younger
      adolescents were concerned with information being disclosed to others (ie, health
      care providers), whereas older adolescents worried more about information being
      disclosed to parents. Other privacy aspects (psychological, social, and physical)
      also were important. To protect psychological privacy, adolescents were cautious
      about revealing sensitive information for fear of being judged by providers. To
      protect social privacy, they were reluctant to talk with unfamiliar or multiple
      providers, and they did not want to discuss issues they perceived as unrelated to
      their health care. Adolescents who commented about physical privacy said that
      they thought about their physical safety during physical examinations, as well as
      their visibility to others, and said that they were more comfortable when
      examinations were performed by female rather than male providers. CONCLUSIONS:
      Adolescents value all aspects of privacy. Providers should address not only
      informational but also psychological, social, and physical privacy to improve the
      care of adolescent patients.

PMID- 21098149
TI  - Food insecurity: could school food supplementation help break cycles of
      intergenerational transmission of social inequalities?
AB  - OBJECTIVE: The aim of our study was to investigate the moderating effect of
      school food programs in schools in disadvantaged neighborhoods on the association
      between household food insecurity and scholastic difficulties among adolescents.
      METHODS: We analyzed data from the Social and Health Survey of Children and
      Adolescents in Quebec, Canada, which was conducted in 1999 and included 2346
      adolescent students 13 and 16 years of age (and 1983 of their parents). Sample
      weighted regression analyses were performed to determine the association between
      household food insecurity and school difficulties and to explore the moderating
      role of food supplementation programs with respect to this association. RESULTS:
      Household food insecurity, which was linked to the indicators of family
      socioeconomic status, was strongly associated with the indicators of scholastic
      difficulties. This association disappeared for adolescents who benefited from
      food supplementation programs in schools in disadvantaged neighborhoods. The risk
      of school activity limitation decreased from OR = 2.76 (95% confidence interval
      [CI]: 1.41-5.41) to OR = 1.57 (95% CI: 1.35-3.40), the risk of below-average
      grades in the language of instruction decreased from OR = 2.19 (95% CI: 1.28
      3.74) to OR = 0.59 (95% CI: 0.21-1.63), the risk of repeating a year decreased
      from OR = 2.14 (95% CI: 1.35-3.40) to OR = 0.87 (95% CI: 0.42-1.81), and the risk
      of self-rated poor academic performance decreased from OR = 1.74 (95% CI: 1.08
      2.81) to OR = 0.81(95% CI: 0.37-1.78). CONCLUSION: School food supplementation is
      a moderating factor in the association between household food insecurity and
      scholastic difficulties for adolescents.

PMID- 21098150
TI  - Adverse events from cough and cold medications after a market withdrawal of
      products labeled for infants.
AB  - OBJECTIVE: A voluntary market withdrawal of orally administered, over-the
      counter, infant cough and cold medications (CCMs) was announced in October 2007.
      The goal of this study was to assess CCM-related adverse events (AEs) among
      children after the withdrawal. METHODS: Emergency department (ED) visits for CCM
      related AEs among children <12 years of age were identified from a nationally
      representative, stratified, probability sample of 63 US EDs, for the 14 months
      before and after announcement of withdrawal. RESULTS: After withdrawal, the
      number and proportion of estimated ED visits for CCM-related AEs involving
      children <2 years of age were less than one-half of those in the prewithdrawal
      period (1248 visits [13.3%] vs 2790 visits [28.7%]; difference: -15.4% [95%
      confidence interval [CI]: -25.9% to -5.0%]), whereas the overall number of
      estimated ED visits for CCM-related AEs for children <12 years of age remained
      unchanged (9408 visits [95% CI: 6874-11 941 visits] vs 9727 visits [95% CI: 6649
      12 805 visits]). During both periods, two-thirds of estimated ED visits involved
      unsupervised ingestions (ie, children finding and ingesting medications).
      CONCLUSIONS: ED visits for CCM-related AEs among children <2 years of age were
      substantially reduced after withdrawal of over-the-counter infant CCMs. Further
      reductions likely will require packaging improvements to reduce harm from
      unsupervised ingestions and continued education about avoiding CCM use for young
      children. Monitoring of CCM-related harm should continue because recommendations
      were updated in October 2008 to avoid the use of CCMs for children <4 years of
      age.

PMID- 21098151
TI  - Late-preterm birth and its association with cognitive and socioemotional outcomes
      at 6 years of age.
AB  - INTRODUCTION: Late-preterm birth (34-36 weeks' gestation) has been associated
      with a risk for long-term cognitive and socioemotional problems. However, many
      studies have not incorporated measures of important contributors to these
      outcomes, and it is unclear whether effects attributed to gestational age are
      separate from fetal growth or its proxy, birth weight for gestational age.
      METHOD: Data came from a study of low- and normal-weight births sampled from
      urban and suburban settings between 1983 and 1985 (low birth weight, n = 473;
      normal birth weight; n = 350). Random sampling was used to pair singletons born
      late-preterm with a term counterpart whose birth weight z score was within 0.1 SD
      of his or her match (n = 168 pairs). With random-effects models, we evaluated
      whether pairs differed in their IQ scores and teacher-reported behavioral
      problems at the age of 6 years. RESULTS: In adjusted models, late-preterm birth
      was associated with an increased risk of full-scale (adjusted odds ratio [aOR]:
      2.35 [95% confidence interval (CI): 1.20-4.61]) and performance (aOR: 2.04 [95%
      CI: 1.09-3.82]) IQ scores below 85. Late-preterm birth was associated with higher
      levels of internalizing and attention problems, findings that were replicated in
      models that used thresholds marking borderline or clinically significant problems
      (aOR: 2.35 [95% CI: 1.28-4.32] and 1.76 [95% CI: 1.04-3.0], respectively).
      CONCLUSIONS: Late-preterm birth is associated with behavioral problems and lower
      IQ at the age of 6, independent of maternal IQ, residential setting, and
      sociodemographics. Future research is needed to investigate whether these
      findings result from a reduction in gestational length, in utero (eg, obstetric
      complications) or ex-utero (eg, neonatal complications) factors marked by late
      preterm birth, or some combination of these factors.

PMID- 21098152
TI  - Influence of birth hospital on outcomes of ductal-dependent cardiac lesions.
AB  - OBJECTIVE: The goal was to determine the effect of birth hospital pediatric
      cardiac specialty center status and neonatal level of care on 90-day mortality
      for infants with ductal-dependent congenital heart disease. METHODS: A population
      based, retrospective, cohort study was conducted in Washington State in 1987
      2006. All infants born in Washington with gestational ages of >=32 weeks and
      birth weights of >=1500 g who were admitted to a Washington hospital for the care
      of a congenital cardiac anomaly likely to be ductal dependent were included.
      Subjects were required to receive a surgical or interventional cardiac procedure
      within 30 days after birth. Birth certificate data were linked with death
      certificate data and hospital administrative records. The exposures of interest
      were birth hospital pediatric cardiac specialty center status and neonatal level
      of care. The primary outcome was death within 90 days. RESULTS: A total of 823
      infants met the inclusion criteria, 285 born at specialty centers and 538 at
      other centers. After adjustment for cardiac diagnoses, other congenital
      anomalies, birth year, maternal income quartile, and definitive-care hospital,
      there was no significant difference in 90-day mortality for infants born at
      specialty centers versus other centers (odds ratio: 1.05 [95% confidence
      interval: 0.65-1.68]). CONCLUSION: For infants with ductal-dependent congenital
      heart disease, there was no difference in 90-day mortality for infants born at
      specialty centers versus other centers in the state of Washington.

PMID- 21098153
TI  - Redefining outcome of first seizures by acute illness.
AB  - BACKGROUND: Seizures are common in children, but the causes and recurrence risk
      for children with a nonfebrile first seizure remain poorly understood. OBJECTIVE:
      In a prospective longitudinal study of children who presented with a first-time
      seizure, we investigated the viral etiology of associated infectious illnesses
      and sought to determine the risk of recurrent seizures stratified by fever and
      type of illness. PATIENTS AND METHODS: Children (aged 6 months to 6 years) were
      enrolled at the time of evaluation for their first seizure and followed monthly
      for up to 5 years. Seizure and illness data were collected through parent
      interviews and medical-record reviews. Stool, serum, and cerebrospinal fluid
      collected within 48 hours of the first seizure were evaluated for viral
      gastrointestinal pathogens. RESULTS: Of the 117 children enrolled, 78 (67%) had
      febrile seizures, 34 (29%) had nonfebrile-illness seizures, and 5 (4%) had
      unprovoked seizures. Children with nonfebrile-illness seizures were more likely
      than those with febrile seizures to have acute gastroenteritis (47% and 28%,
      respectively; P = .05). No significant differences in seizure recurrence were
      found between children with or without a fever at first seizure. Children with
      acute gastroenteritis at first seizure, regardless of fever, had a lower risk of
      seizure recurrence compared with children with other acute illnesses (hazard
      ratio: 0.28; 95% confidence interval: 0.09-0.80). CONCLUSIONS: Our results
      confirm the role of gastrointestinal illness as a distinguishing feature in
      childhood seizures. Children with this distinct presentation have a low rate of
      seizure recurrence and few neurologic complications.

PMID- 21098154
TI  - Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV
      bronchiolitis.
AB  - BACKGROUND: The trends in hospitalization rates and risk factors for severe
      bronchiolitis have not been recently described, especially after the routine
      implementation of prophylaxis for respiratory syncytial virus (RSV) infections.
      OBJECTIVES: To define the burden of hospitalizations related to RSV and non-RSV
      bronchiolitis in a tertiary-care children's hospital from 2002 to 2007 and to
      identify the risk factors associated with severe disease. METHODS: Medical
      records of patients hospitalized for bronchiolitis were reviewed for demographic,
      clinical, microbiologic, and radiologic characteristics as well as the presence
      of underlying medical conditions. Differences were evaluated between children
      with RSV and non-RSV bronchiolitis, and multivariable logistic regression
      analyses were performed to identify independent risk factors for severe disease.
      RESULTS: Bronchiolitis hospitalizations in children younger than 2 years old (n =
      4800) significantly increased from 536 (3.3%) in 2002 to 1241 (5.5%) in 2007,
      mainly because of RSV infections. Patients with RSV bronchiolitis (n = 2840
      [66%]) were younger at hospitalization and had a lower percentage of underlying
      medical conditions than children hospitalized with non-RSV bronchiolitis (27 vs
      37.5%; P < .001). However, disease severity defined by length of hospitalization
      and requirement of supplemental oxygen, intensive care, and mechanical
      ventilation was significantly worse in children with RSV bronchiolitis. RSV
      infection and prematurity, regardless of the etiology, were identified as
      independent risk factors for severe bronchiolitis. CONCLUSIONS: There was a
      significant increase in hospitalizations for RSV bronchiolitis from 2002 to 2007.
      A majority of the children with RSV bronchiolitis were previously healthy, but
      their disease severity was worse compared with those hospitalized with non-RSV
      bronchiolitis.

PMID- 21098155
TI  - Febrile infants with urinary tract infections at very low risk for adverse events
      and bacteremia.
AB  - BACKGROUND: There is limited evidence from which to derive guidelines for the
      management of febrile infants aged 29 to 60 days with urinary tract infections
      (UTIs). Most such infants are hospitalized for >=48 hours. Our objective was to
      derive clinical prediction models to identify febrile infants with UTIs at very
      low risk of adverse events and bacteremia in a large sample of patients. METHODS:
      This study was a 20-center retrospective review of infants aged 29 to 60 days
      with temperatures of >=38 degrees C and culture-proven UTIs. We defined UTI by
      growth of >=50,000 colony-forming units (CFU)/mL of a single pathogen or >=10,000
      CFU/mL in association with positive urinalyses. We defined adverse events as
      death, shock, bacterial meningitis, ICU admission need for ventilator support, or
      other substantial complications. We performed binary recursive partitioning
      analyses to derive prediction models. RESULTS: We analyzed 1895 patients. Adverse
      events occurred in 51 of 1842 (2.8% [95% confidence interval (CI): 2.1%-3.6%)]
      and bacteremia in 123 of 1877 (6.5% [95% CI: 5.5%-7.7%]). Patients were at very
      low risk for adverse events if not clinically ill on emergency department (ED)
      examination and did not have a high-risk past medical history (prediction model
      sensitivity: 98.0% [95% CI: 88.2%-99.9%]). Patients were at lower risk for
      bacteremia if they were not clinically ill on ED examination, did not have a high
      risk past medical history, had a peripheral band count of <1250 cells per MUL,
      and had a peripheral absolute neutrophil count of >=1500 cells per MUL
      (sensitivity 77.2% [95% CI: 68.6%-84.1%]). CONCLUSION: Brief hospitalization or
      outpatient management with close follow-up may be considered for infants with
      UTIs at very low risk of adverse events.

PMID- 21098156
TI  - Therapeutic acetaminophen is not associated with liver injury in children: a
      systematic review.
AB  - BACKGROUND: Concern exists about the potential for liver injury with therapeutic
      dosing of acetaminophen in children. OBJECTIVE: We systematically reviewed the
      medical literature to determine the rate at which liver injury has been reported
      for children prescribed therapeutic doses of acetaminophen (<=75 mg/kg per day
      orally or intravenously or <=100 mg/kg per day rectally). METHODS: We searched
      Medline, Embase, and the Cochrane Central Register of Controlled Trials to locate
      all studies in which acetaminophen was administered to a defined pediatric
      population for >=24 hours and for all case reports of liver injury after
      therapeutic acetaminophen dosing. Trained reviewers extracted data from each
      report. Major and minor hepatic adverse events (AEs) were defined prospectively.
      Causality was assessed by using the Naranjo algorithm. RESULTS: A total of 62
      studies that enrolled 32,414 children were included. No child (0% [95% confidence
      interval: 0.000-0.009]) was reported to have exhibited signs or symptoms of liver
      disease, to have received an antidote or transplantation, or to have died. Major
      or minor hepatic AEs were reported for 10 children (0.031% [95% confidence
      interval: 0.015-0.057]). The highest transaminase value reported was 600 IU/L.
      Naranjo scores (2-3) suggested "possible" causation. Twenty-two case reports were
      identified. In 9 cases, the Naranjo score suggested "probable" causation (5-6).
      CONCLUSIONS: Hepatoxicity after therapeutic dosing of acetaminophen in children
      is rarely reported in defined-population studies. Case reports suggest that this
      phenomenon may occur, but few reports contain sufficient data to support a
      probable causal relationship.

PMID- 21098158
TI  - Radiological reasoning: dilated coronary arteries.

PMID- 21098159
TI  - AJR teaching file: a right paracardiac mass in a patient with a history of
      coronary artery bypass grafting.

PMID- 21098160
TI  - Eponyms of tumors and tumor-like lesions in the musculoskeletal system: who were
      the people and what are the lesions? Pictorial review.

PMID- 21098162
TI  - Imaging of necrotizing fasciitis: self-assessment module.
AB  - The educational objectives for this self-assessment module are for the
      participant to exercise, self-assess, and improve his or her understanding of the
      clinical and imaging features of necrotizing fasciitis and the role of imaging in
      the clinical management of patients with necrotizing fasciitis.

PMID- 21098163
TI  - AJR teaching file: aortic valve abnormality in a woman with progressive shortness
      of breath.

PMID- 21098157
TI  - Survival and morbidity outcomes for very low birth weight infants with Down
      syndrome.
AB  - OBJECTIVE: Our objective was to compare survival and neonatal morbidity rates
      between very low birth weight (VLBW) infants with Down syndrome (DS) and VLBW
      infants with non-DS chromosomal anomalies, nonchromosomal birth defects (BDs),
      and no chromosomal anomaly or major BD. METHODS: Data were collected
      prospectively for infants weighing 401 to 1500 g who were born and/or cared for
      at one of the study centers participating in the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development Neonatal Research Network in 1994
      2008. Risk of death and morbidities, including patent ductus arteriosus (PDA),
      necrotizing enterocolitis (NEC), late-onset sepsis (LOS), retinopathy of
      prematurity, and bronchopulmonary dysplasia (BPD), were compared between VLBW
      infants with DS and infants in the other groups. RESULTS: Infants with DS were at
      increased risk of death (adjusted relative risk: 2.47 [95% confidence interval:
      2.00-3.07]), PDA, NEC, LOS, and BPD, relative to infants with no BDs. Decreased
      risk of death (relative risk: 0.40 [95% confidence interval: 0.31-0.52]) and
      increased risks of NEC and LOS were observed when infants with DS were compared
      with infants with other non-DS chromosomal anomalies. Relative to infants with
      nonchromosomal BDs, infants with DS were at increased risk of PDA and NEC.
      CONCLUSION: The increased risk of morbidities among VLBW infants with DS provides
      useful information for counseling parents and for anticipating the need for
      enhanced surveillance for prevention of these morbidities.

PMID- 21098164
TI  - AJR teaching file: fat-containing mass in the interatrial septum.

PMID- 21098165
TI  - AJR teaching file: periarticular calcifications in two patients with acute hand
      pain.

PMID- 21098167
TI  - Adrenal imaging: why, when, what, and how? Part 1. Why and when to image?

PMID- 21098166
TI  - Extravasation of iodinated contrast medium during CT: self-assessment module.
AB  - The educational objectives for this self-assessment module on the extravasation
      of iodinated contrast medium are for the participant to exercise, self-assess,
      and improve his or her understanding of the frequency, appearance, recognition,
      and management of extravasation of iodinated contrast medium during contrast
      enhanced CT.

PMID- 21098168
TI  - Revising a manuscript: ten principles to guide success for publication.
AB  - OBJECTIVE: The process of revising a manuscript and successfully responding to
      the comments of reviewers and the Editor can be difficult. This article provides
      some practical steps to guide authors in this task and attain publication of
      their manuscript. CONCLUSION: Following the principles outlined in this article
      will enable authors to successfully meet the challenges of manuscript revision
      and hasten the route to publication.

PMID- 21098169
TI  - Quantitative analysis of intracranial hypostasis: comparison of early postmortem
      and antemortem CT findings.
AB  - OBJECTIVE: The purpose of this study was to quantitatively analyze postmortem
      hypostasis in the intracranial venous sinus on head CT scans compared with the
      antemortem CT findings in the same patients with the aim of evaluating
      sedimentation in the heart and great vessels. MATERIALS AND METHODS: A total of
      50 patients on whom head CT was performed before and after death were enrolled.
      Attenuation in the dorsal part of the superior sagittal sinus was measured at the
      level of the basal ganglia on both antemortem and postmortem CT scans. Increased
      attenuation in the transverse sinus and cerebellar tentorium and sedimentation in
      the heart and great vessels were evaluated visually. RESULTS: Attenuation in the
      dorsal part of the superior sagittal sinus increased significantly (p < 0.0001)
      between antemortem (42.77 +/- 6.23 HU) and postmortem (49.72 +/- 10.58 HU) CT in
      80% of cases. Increased attenuation of the transverse sinus or cerebellar
      tentorium was observed in 48% of cases and sedimentation in the heart or great
      vessels in 62% of cases. Increased attenuation in the superior sagittal sinus was
      clearly evident in patients with sedimentation in the heart or great vessels
      (antemortem, 43.81 +/- 6.17 HU; postmortem, 54.65 +/- 8.51 HU) compared with the
      patients without evidence of sedimentation (antemortem, 41.06 +/- 6.10 HU;
      postmortem, 41.66 +/- 8.57 HU) (p < 0.0001). CONCLUSION: Intracranial hypostasis
      is a common postmortem CT finding. Radiologists and physicians who interpret
      postmortem neurologic images should be aware of intracranial hypostasis and
      differentiate this phenomenon from intracranial hemorrhage.

PMID- 21098170
TI  - MRI of cardiac involvement in transthyretin familial amyloid polyneuropathy.
AB  - OBJECTIVE: The purpose of this study was to evaluate cardiac MRI features in a
      group of patients with transthyretin familial amyloid polyneuropathy (FAP).
      SUBJECTS AND METHODS: Sixteen patients with transthyretin FAP underwent 2D
      echocardiography with Doppler examination, cardiac MRI, and (99m)Tc-diphosphonate
      (DPD) scintigraphy. Four patients had peripheral polyneuropathy, three had carpal
      tunnel syndrome, one patient had symptoms and signs of heart failure, and eight
      patients had no symptoms but had a family history of FAP. At MRI, cardiac
      function parameters and delayed contrast enhancement findings were evaluated.
      RESULTS: Six patients had cardiac radiotracer uptake at scintigraphy (FAP cardiac
      group), and 10 patients had no cardiac uptake (FAP noncardiac group). The FAP
      cardiac group included the four patients with peripheral neuropathy, one patient
      with carpal tunnel syndrome, and the only patient with heart failure. At MRI,
      abnormal contrast enhancement was found in all patients with positive
      scintigraphic findings and in no patient with negative scintigraphic findings.
      All patients had involvement of the left ventricle and other chambers or
      structures (atria, right ventricle, tricuspid valve leaflets). Left ventricular
      contrast enhancement was focal in four patients, subendocardial circumferential
      in one patient, and diffuse in one patient. The only patient with signs of heart
      failure had circumferential subendocardial enhancement. CONCLUSION: Cardiac
      contrast-enhanced MRI can be used to identify cardiac amyloidosis in patients
      with FAP who do not have clinical signs of heart involvement. In these patients,
      the typical subendocardial circumferential pattern of contrast enhancement is
      rare. We observed unusual enhancement patterns as focal or diffuse left
      ventricular enhancement accompanied by enhancement of the atria, tricuspid valve,
      or right ventricle.

PMID- 21098171
TI  - C-arm cone-beam CT-guided percutaneous transthoracic lung biopsy: usefulness in
      evaluation of small pulmonary nodules.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of C-arm
      conebeam CT-guided percutaneous transthoracic lung biopsy of small (<= 2 cm) lung
      nodules. MATERIALS AND METHODS: Twenty-seven patients who underwent C-arm cone
      beam CT-guided percutaneous transthoracic lung biopsy of small (<= 2 cm) lung
      nodules were enrolled in the study. The mean nodule size was 13 +/- 4 mm in
      diameter. These lesions were divided into two groups according to size: 10
      lesions 1 cm or smaller and 17 lesions larger than 1 cm. The diagnostic accuracy,
      sensitivity, and specificity in the two groups were compared by use of Fisher's
      exact test. Radiation dose in a female humanoid phantom was measured with
      radiophotoluminescent glass dosimeters. The average patient dose was calculated.
      RESULTS: Eighteen malignant (67%) and eight benign (30%) nodules and one (3%)
      indeterminate nodule were found. The overall sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy were 94%, 89%, 94%,
      89%, and 92%. The sensitivity, specificity, and accuracy were 100%, 75%, and 90%
      for the lesions 1 cm or smaller and 91%, 100%, and 94% for the lesions larger
      than 1 cm. The accuracy, sensitivity, and specificity did not differ
      significantly between the groups (all p > 0.05, Fisher's exact test). The average
      radiation dose among 27 patients was 4.6 mSv (range, 2.19-9.37). CONCLUSION: C
      arm cone-beam CT-guided percutaneous transthoracic lung biopsy is a useful
      diagnostic technique in the evaluation of small lung nodules.

PMID- 21098172
TI  - Persistent pure ground-glass nodules in the lung: interscan variability of
      semiautomated volume and attenuation measurements.
AB  - OBJECTIVE: The purpose of this article is to assess the interscan variability of
      semiautomated volume and attenuation measurements for pulmonary persistent pure
      ground-glass nodules. SUBJECTS AND METHODS: Thirty pure ground-glass nodules in
      25 patients referred for known pure ground-glass nodules were evaluated with two
      consecutive unenhanced chest CT examinations performed within 10 minutes. For the
      second limited scan, patients were asked to first get off and then get back on
      the table to simulate a follow-up examination. CT images were reconstructed using
      two different algorithms (sharp, B60F; medium sharp, B50F). Two chest
      radiologists independently measured the volumes and attenuations of pure ground
      glass nodules, twice on the first CT scan and once on the second CT scan, using
      commercial software. Interscan variability was measured using the Bland-Altman
      method. RESULTS: Nodule segmentation was successful in 98.3% (177/180) and 97.8%
      (176/180) of measurements with B60F and B50F, respectively. With respect to
      volume measurements, interscan variability for reviewer 1 was -17.7% to 18.3%
      with B60F and -18.8% to 15.7% with B50F; interscan variability for reviewer 2 was
      -18.6% to 18.9% with B60F and -15.6% to 17.2% with B50F. With respect to
      attenuation measurements, interscan variability for reviewer 1 was -7.2% to 7.9%
      with B60F and -7.9% to 9.4% with B50F; interscan variability for reviewer 2 was 
      7.7% to 8.1% with B60F and -8.5% to 9.9% for B50F. CONCLUSION: Variations in
      volume and attenuation measurements of persistent pure ground-glass nodules using
      commercial software were reasonably small, allowing the detection of clinically
      relevant growth.

PMID- 21098173
TI  - Hypervascular gastric masses: CT findings and clinical correlates.
AB  - OBJECTIVE: This article focuses on masses that are hypervascular on IV contrast
      enhanced CT. CONCLUSION: The rising use of dual-phase IV contrast-enhanced CT
      will result in an increase in incidental detection of hypervascular gastric
      masses. Radiologists must be aware of the range of abnormalities that may appear
      as a hyperenhancing gastric mass because the differential diagnosis includes both
      benign and malignant lesions.

PMID- 21098174
TI  - MRI features of renal oncocytoma and chromophobe renal cell carcinoma.
AB  - OBJECTIVE: The purpose of this study was to retrospectively describe the MRI
      features of the pathologically related entities renal oncocytoma and chromophobe
      renal cell carcinoma (RCC). MATERIALS AND METHODS: Twenty-eight cases of
      histologically proven renal oncocytoma and 15 of chromophobe RCC evaluated with
      preoperative MRI from January 2003 through June 2009 at our institution were
      independently reviewed for an array of MRI features by two radiologists blinded
      to the final histopathologic diagnosis. These features were tabulated and
      compared between chromophobe RCC and renal oncocytoma by use of the Mann-Whitney
      test and binary logistic regression. RESULTS: Renal oncocytoma and chromophobe
      RCC showed no significant difference in size or any of 16 qualitative imaging
      features (p = 0.0842-1.0, reader 1; p = 0.0611-1.0, reader 2). Microscopic fat,
      hemorrhage, cysts, infiltrative margins, perinephric fat invasion, renal vein
      invasion, enhancement homogeneity, and hypervascularity were each observed in
      less than 20% of cases by both readers. A central scar and segmental enhancement
      inversion (a recently described finding in which early contrast-enhanced images
      show relatively more enhanced and less enhanced intralesional components with
      inversion of their relative enhancement on later images) were observed by both
      readers in at least 10% of cases of both renal oncocytoma and of chromophobe RCC
      with no significant difference between the two entities (p = 0.2092-0.2960).
      CONCLUSION: We have presented the largest series to date of the MRI features of
      both renal oncocytoma and chromophobe RCC. These related entities exhibited
      similar findings, and no MRI features were reliable in distinguishing between
      them.

PMID- 21098175
TI  - Sonography of the anterior oblique ligament of the trapeziometacarpal joint: a
      study of cadavers and asymptomatic volunteers.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of ultrasound to
      identify and characterize the anterior oblique ligament of the thumb in cadavers
      and asymptomatic volunteers. SUBJECTS AND METHODS: The anterior oblique ligaments
      of four cadaveric hands were imaged with a high-resolution transducer. The
      ligaments were then injected with 0.1% methylene blue using ultrasound guidance.
      To confirm identification of the ligament, the base of the thumb was immediately
      dissected, revealing the exact location of the dye. The bilateral ligaments in 40
      asymptomatic adult volunteers were imaged. RESULTS: Surgical dissection confirmed
      injection of methylene blue into all cadaveric ligaments. The proximal attachment
      of the anterior oblique ligament was well defined in all the hands, and the
      distal attachment was well defined in 94% of the hands. The mean thickness of the
      anterior oblique ligament at the metacarpal attachment (0.7 mm), midportion (0.98
      mm), and trapezial attachment (0.65 mm) did not differ significantly with respect
      to sex, right and left side, or hand dominance and was weakly correlated with
      weight, height, body mass index, and age. The length of the ligament was
      statistically significantly different between the dominant (10.6 mm) and
      nondominant (9.6 mm) hands. The volar metacarpal translation with palmar
      abduction stress did not differ significantly between the dominant (0.7 mm) and
      nondominant (0.8 mm) hands. There was no association between the degree of
      translation and the biologic characteristics (weight, height, body mass index,
      and age). CONCLUSION: High-resolution ultrasound can be used to identify and
      measure the thickness of the anterior oblique ligament. Dynamic ultrasound
      imaging can depict volar translation of the metacarpal, which may facilitate
      diagnosis of ligamentous injury.

PMID- 21098176
TI  - CT-guided sternoclavicular joint injections: description of the procedure,
      reliability of imaging diagnosis, and short-term patient responses.
AB  - OBJECTIVE: The purpose of this study was to evaluate pain relief 20 to 30 minutes
      after diagnostic or therapeutic injections into the sternoclavicular joint and to
      compare patient outcomes based on the CT diagnosis. MATERIALS AND METHODS:
      Informed consent was obtained from each patient. Ethics approval was not
      required. Fifty patients who had CT-guided injections of corticosteroid and local
      anesthetic into their sternoclavicular joints were included in the study.
      Preinjection and 20- to 30-minute postinjection visual analog scale data were
      recorded and compared with the imaging findings agreed by consensus. Kappa
      statistics were calculated for the reliability of imaging diagnosis. The
      percentage of patients improving after joint injection was calculated, and the
      risk ratio comparing the response of patients with osteoarthritis to those
      without osteoarthritis was completed. The correlation between the severity of
      each patient's osteoarthritis and the pain response was calculated using
      Spearman's correlation coefficient. RESULTS: Sixty-six percent of the patients
      reported clinically significant pain reduction at between 20 and 30 minutes after
      injection. The proportion of patients with osteoarthritis who had a clinically
      significant response was 67% compared with 64% for patients who did not have
      osteoarthritis. This difference was not statistically or clinically significant.
      There was no correlation between the severity of osteoarthritis and the amount of
      pain reduction (r = 0.03). The reliability of imaging diagnosis was substantial.
      CONCLUSION: Two thirds of patients having sternoclavicular joint injections of
      corticosteroids and local anesthetics report clinically significant improvement
      regardless of the abnormalities detected on their CT images.

PMID- 21098177
TI  - Ultrasound detection of rotator cuff tears: observer agreement related to
      increasing experience.
AB  - OBJECTIVE: Ultrasound of the rotator cuff is considered to be operator-dependent
      with its accuracy being related to the operator's level of experience. This study
      was conducted to test the hypothesis that ultrasound performed by operators with
      different levels of experience will give nonreproducible results. SUBJECTS AND
      METHODS: Two radiologists, one general radiologist with no experience in
      musculoskeletal ultrasound and one experienced musculoskeletal radiologist,
      independently performed ultrasound on 200 shoulders in 183 consecutive patients.
      Agreement was assessed. Cohen's kappa values with standard errors were
      calculated. In 71 patients the ultrasound findings could be related to surgical
      findings. RESULTS: The diagnoses of full-thickness and partial-thickness rotator
      cuff tears were made with agreements of 98% (kappa-value: 0.95 [standard error,
      0.03]) and 90% (kappa-value: 0.79 [0.05]), respectively. Agreement for full
      thickness tears was constant; the agreement for partial-thickness tears improved
      from 80% to 98% in the last quarter of the study period. Based on the 71 patients
      who underwent shoulder surgery, sensitivity, specificity, and accuracy for
      detecting full-thickness tears by the experienced and general radiologists were
      94%, 94%, and 94% and 89%, 91%, and 90%, respectively. Sensitivity, specificity,
      and accuracy for detecting partial-thickness tears by the experienced and general
      radiologists were 100%, 32%, and 57% and 84%, 35%, and 53%, respectively.
      CONCLUSION: The hypothesis that ultrasound of the shoulder is operator-dependent
      and related to experience was refuted. In this study, there was excellent
      agreement for the detection of rotator cuff tears, which only slightly improved
      with the increasing experience of the general radiologist. Accuracy of rotator
      cuff tear detection was high and in accordance with the results in the
      literature.

PMID- 21098178
TI  - Lisfranc joint ligamentous complex: MRI with anatomic correlation in cadavers.
AB  - OBJECTIVE: The aim of our study was to clarify the ligamentous anatomy of the
      Lisfranc joint complex and show the diagnostic capability of MRI in the
      assessment of the Lisfranc joint complex with detailed anatomic correlation in
      cadavers. MATERIALS AND METHODS: Ten fresh cadaveric feet were studied with high
      spatial-resolution MRI before and after the intraarticular injection of a
      gadopentetate dimeglumine solution. MR images were evaluated by two readers in
      consensus, with emphasis on the visibility of the ligamentous structures and
      their appearance. Readers also measured the dimensions (length, width, and
      thickness) of the Lisfranc ligament and of the first plantar tarsometatarsal
      ligament, or plantar Lisfranc ligament. For anatomic analysis, nine cadaveric
      specimens were sectioned in 3-mm-thick slices in the same planes used during MRI.
      One additional foot specimen was used for dissection. RESULTS: In all 10
      cadaveric specimens we were able to identify and characterize with MRI the
      different ligamentous elements that contribute to the overall stability of the
      Lisfranc joint complex. CONCLUSION: By clearly defining the normal ligaments that
      contribute to the stability of the Lisfranc joint, MRI allows a more precise and
      correct diagnosis of the origin of the Lisfranc joint instability, perhaps
      permitting a more specific surgical management. MRI also allows a better
      understanding of the normal imaging anatomy of the different ligamentous
      components of the Lisfranc joint, mainly of the Lisfranc and plantar Lisfranc
      ligaments.

PMID- 21098179
TI  - Correlation of apparent diffusion coefficient and fractional anisotropy values in
      the developing infant brain.
AB  - OBJECTIVE: The purpose of our study was to correlate decrease in apparent
      diffusion coefficient (ADC) and increase in fractional anisotropy (FA) in various
      white matter (WM) regions using diffusion tenor imaging (DTI) within the first
      year of life. MATERIALS AND METHODS: We performed DTI on 53 infants and measured
      FA and ADC within 10 WM regions important in brain development. For each region,
      we calculated the slope of ADC as a function of FA, the correlation coefficient
      (r) and correlation of determination (r(2)). We performed a group analysis of r
      values and r(2)values for six WM regions primarily composed of crossing fibers
      and four regions primarily having parallel fibers. Upon finding that a strong
      correlation of FA with age existed, we adjusted for age and calculated partial
      correlation coefficients. RESULTS: Slopes of FA versus ADC ranged from -1.00711
      to -1.67592 (p < 0.05); r values ranged from -0.81 to -0.50 and r(2) values from
      0.25 to 0.66. The four greatest r(2) values were within WM regions having large
      numbers of crossing fibers and the three lowest r(2) values were in regions
      having predominantly parallel fibers. After adjusting for age, slopes ranged from
      -1.08095 to 0.09612 (p < 0.05 in five cases); partial correlation coefficients
      ranged from -0.49 to 0.03 and r(2) values from 0.31 to 0.79. The highest partial
      correlation coefficients were then relatively equally distributed between the two
      types of WM regions. CONCLUSION: In various regions, FA and ADC evolved with
      differing degrees of correlation. We found a strong influence of age on the
      relationship between FA and ADC.

PMID- 21098181
TI  - Addendum reports.

PMID- 21098180
TI  - A comparative analysis of PTFE-covered and uncovered stents for palliative
      treatment of malignant extrahepatic biliary obstruction.
AB  - OBJECTIVE: The purpose of our study was to evaluate the outcomes of the newly
      designed partially polytetrafluoroethylene (PTFE)-covered stent and compare the
      outcomes of PTFE-covered and uncovered stents in patients with malignant
      extrahepatic biliary obstruction. MATERIALS AND METHODS: From March 2006 to
      December 2008, 58 consecutive patients who underwent PTFE-covered stent placement
      were prospectively studied. Those data were compared with data obtained by
      retrospectively studying 58 consecutive patients who underwent self-expanding
      uncovered stent placement from March 2003 to February 2006. RESULTS: According to
      the Kaplan-Meier analysis, the cumulative stent patency of covered stents (98%,
      98%, 91%, 76%, and 76% at 1, 3, 6, 9, and 12 months, respectively) was
      significantly better than that of uncovered stents (98%, 83%, 72%, 57%, and 57%
      at 1, 3, 6, 9, and 12 months, respectively) (p = 0.037). There was no significant
      difference in the patient survival between the groups (p = 0.479). The two groups
      also did not significantly differ in terms of complication rate (p = 0.717), with
      8.6% (5/58) in the covered stent group and 5.2% (3/58) in the uncovered stent
      group. CONCLUSION: Partially PTFE-covered stents are effective and safe for the
      palliative treatment of malignant extrahepatic biliary obstruction. Moreover,
      PTFE-covered stents were significantly superior to uncovered stents in terms of
      stent patency for palliative treatment of patients with malignant extrahepatic
      biliary obstruction. In addition, there was no significant difference in patient
      survival and complication rate between the PTFE-covered and uncovered stent
      group.

PMID- 21098182
TI  - Communication of unexpected abnormalities.

PMID- 21098183
TI  - Biopsy of thyroid nodules: comparison of three sets of guidelines.

PMID- 21098184
TI  - Role of ultrasound in the assessment of the sentinel node of melanoma patients.

PMID- 21098185
TI  - Rate of resolution of pulmonary emboli at different orders of pulmonary arteries.

PMID- 21098186
TI  - ARRS, your trusted partner in lifelong learning.

PMID- 21098187
TI  - Assessment of Agatston coronary artery calcium score using contrast-enhanced CT
      coronary angiography.
AB  - OBJECTIVE: The purpose of this article is to evaluate to what extent Agatston
      scores may be derived from CT coronary angiography (CTA) examinations, compared
      with traditional unenhanced CT calcium scores. MATERIALS AND METHODS: Fifty
      patients with a CT calcium score-Agatston score of zero and 50 patients with a CT
      calcium score-Agatston score of 1 or greater whose CT calcium scores had been
      calculated and who had undergone CTA using volumetric 320-MDCT were included.
      Agatston scores were obtained at 3.0-mm slices for CT calcium score and CTA.
      Method agreement, interobserver agreement, and diagnostic performance of CTA for
      detecting coronary calcium were evaluated. RESULTS: Of 50 patients with a
      positive CT calcium score-Agatston score, coronary artery calcium was detected
      with CTA in 43 patients by observer 1 (mean CTA score, 102 +/- 202; mean CT
      calcium score, 254 +/- 501) and in 46 patients by observer 2 (mean CTA score, 94
      +/- 147; mean CT calcium score, 272 +/- 531). Of the 50 patients with a CT
      calcium score-Agatston score of zero, 49 (98%, observer 1) and 50 (100%, observer
      2) had a zero score with CTA as well. An intraclass correlation of 0.78 and 0.62
      was found between CT calcium score and CTA (p < 0.01), whereas higher Agatston
      scores were underestimated with CTA. For observer 1, the sensitivity,
      specificity, positive predictive value, negative predictive value, and diagnostic
      accuracy for detection of coronary calcium with CTA were 86%, 98%, 98%, 88%, and
      92%, respectively, and the corresponding values for observer 2 were 92%, 100%,
      100%, 93%, and 96%, respectively. Interobserver agreement was 0.996 for CT
      calcium score and 0.93 for CTA. CONCLUSION: Coronary artery calcium can be
      detected on CTA images with high accuracy. The Agatston calcium score derived
      from CTA images shows good correlation with unenhanced CT calcium score and is
      highly reproducible. However, higher Agatston scores are systematically
      underestimated when derived from CTA images.

PMID- 21098188
TI  - Feasibility and radiation dose of high-pitch acquisition protocols in patients
      undergoing dual-source cardiac CT.
AB  - OBJECTIVE: The objective of this study was to compare image quality and radiation
      dose between high-pitch and established retrospectively and prospectively gated
      cardiac CT protocols using an Alderson-Rando phantom and a set of patients.
      MATERIALS AND METHODS: An anthropomorphic Alderson-Rando phantom equipped with
      thermoluminiscent detectors and a set of clinical patients underwent the
      following cardiac CT protocols: high-pitch acquisition (pitch 3.4), prospectively
      triggered acquisition, and retrospectively gated acquisition (pitch 0.2). For
      patients with sinus rhythm below 65 beats per minute (bpm), high-pitch protocol
      was used, whereas for patients in sinus rhythm between 65 and 100 bpm,
      prospective triggering was used. Patients with irregular heart rates or heart
      rates of >= 100 bpm, were examined using retrospectively gated acquisition.
      Evaluability of coronary artery segments was determined, and effective radiation
      dose was derived from the phantom study. RESULTS: In the phantom study, the
      effective radiation dose as determined with thermoluminescent detector (TLD)
      measurements was lowest in the high-pitch acquisition (1.21, 3.12, and 11.81 mSv,
      for the high-pitch, the prospectively triggered, and the retrospectively gated
      acquisition, respectively). There was a significant difference with respect to
      the percentage of motion-free coronary artery segments (99%, 87%, and 92% for
      high-pitch, prospectively triggered, and retrospectively gated, respectively (p <
      0.001), whereas image noise was lowest for the high-pitch protocol (p < 0.05).
      CONCLUSION: High-pitch scans have the potential to reduce radiation dose up to
      61.2% and 89.8% compared with prospectively triggered and retrospectively gated
      scans. High-pitch protocols lead to excellent image quality when used in patients
      with stable heart rates below 65 bpm.

PMID- 21098189
TI  - Three-dimensional MDCT for preoperative local staging of gastric cancer using gas
      and water distention methods: a retrospective cohort study.
AB  - OBJECTIVE: The purpose of this article is to compare the T-staging accuracy and
      lesion detectability of MDCT with gas distention versus water distention
      according to the surgical and histopathologic findings, for the preoperative
      evaluation of gastric cancer. MATERIALS AND METHODS: For a 3-month period, 113
      consecutive patients (72 men and 41 women; age range, 23-85 years; mean age, 58
      years) with 116 surgically confirmed gastric cancers from a single institution
      were included in our study. All patients had undergone preoperative MDCT with
      either effervescent granules taken orally (n = 55) or after having drunk 1,000 mL
      of tap water (n = 58) to create gastric distention. In addition to transverse
      images, multiplanar reformation images and 3D surface shaded display images were
      also obtained with gas distention CT, and multiplanar reformation images were
      obtained with water distention CT. The CT images were retrospectively reviewed by
      two abdominal radiologists separately with regard to T staging and lesion
      detectability. The accuracy values were compared between the two methods using
      Fisher's exact test. RESULTS: The T-staging accuracy for gastric cancer did not
      differ significantly between gas distention and water distention CT scans,
      according to both radiologists (p > 0.05). Furthermore, the staging accuracy
      values for T1a cancers on gas distention CT scans for radiologists 1 and 2 were
      also comparable with those of water distention CT scans (91.1% vs 85% for
      radiologist 1 and 89.3% vs 85% for radiologist 2; p > 0.05). However, the tumor
      detection rate was significantly higher on gas distention CT scans using 2D and
      surface shaded display images for both radiologists (94.6% for radiologist 1 and
      91.1% for radiologist 2), compared with the rates for water distention CT scans
      (78.3% and 73.3%) or gas distention CT scans using only 2D images (75.0% and
      67.9%) (p < 0.05). CONCLUSION: MDCT using the gas distention technique showed
      performance comparable to that of the water distention technique for the T
      staging of preoperative gastric cancer with better lesion detectability.

PMID- 21098190
TI  - MR imaging features of small solid pseudopapillary tumors: retrospective
      differentiation from other small solid pancreatic tumors.
AB  - OBJECTIVE: The purpose of this study was to describe the MRI features of small
      solid pseudopapillary tumors useful for differentiating these tumors from other
      small solid pancreatic tumors. MATERIALS AND METHODS: Forty-five patients (18
      men, 27 women; mean age, 59 +/- 11.7 years) with 45 solid pancreatic tumors
      smaller than 3 cm in diameter registered from 2000 to 2009 were included. Twenty
      two of the tumors were adenocarcinomas, 12 were endocrine tumors, and 11 were
      solid pseudopapillary tumors. Two radiologists analyzed the MR images for
      morphologic features, signal intensity of the lesion on unenhanced images, and
      dynamic enhancement pattern. The contrast-to-noise ratio between the lesion and
      the pancreas was calculated on T1- and T2-weighted images and on dynamic images.
      RESULTS: Solid pseudopapillary tumors commonly had the following features:
      completely well-defined margin (82%), pure solid consistency (82%), low signal
      intensity on unenhanced T1-weighted images (100%), high signal intensity on T2
      weighted images (100%), a strong predominance among women (91%), and early
      heterogeneous and slowly progressive enhancement (100%). The solid
      pseudopapillary tumors rarely had a capsule or hemorrhage. A characteristic
      qualitative feature of solid pseudopapillary tumors that was significantly
      different from the other two tumor types was very high signal intensity on T2
      weighted images (p < 0.01). Quantitative analysis showed that the solid
      pseudopapillary tumors had a lower contrast-to-noise ratio (-16.82 +/- 5.84) on
      T1-weighted images and a higher contrast-to-noise ratio (37.35 +/- 33.59) on T2
      weighted images than did the other two tumor types (p < 0.01). CONCLUSION: Small
      solid pseudopapillary tumors were predominantly seen as completely well
      demarcated pure solid tumors in middle-aged women. They had lower signal
      intensity on T1-weighted images and higher signal intensity on T2-weighted images
      than did the other two tumor types and had early heterogeneous and progressive
      enhancement.

PMID- 21098191
TI  - Adrenal hematoma after nephrectomy.
AB  - OBJECTIVE: The objective of our study was to retrospectively define the incidence
      of adrenal hematoma on CT or MRI after nephrectomy. MATERIALS AND METHODS:
      Between January 2008 and June 2009, 465 patients underwent nephrectomy at our
      institution. Of these, patients without both preoperative and postoperative
      abdominal CT or MR studies within 6 months of surgery (n = 83) and those with
      documented adrenalectomy at the time of radical nephrectomy (n = 33) were
      excluded. Thus, 349 patients (292 male, 57 female; mean age, 60.2 years; range, 2
      88 years) were included in the study. Preoperative and postoperative CT or MR
      studies were reviewed by two radiologists in consensus for the presence or
      absence of adrenal hematoma. Diagnosis of adrenal hematoma was made by imaging
      findings and follow-up. The incidence of adrenal hematoma was calculated with a
      95% CI. RESULTS: Of the 349 patients (partial nephrectomy, n = 232; radical
      nephrectomy, n = 117), 19 patients developed adrenal hematoma after nephrectomy
      (partial nephrectomy, n = 12; radical nephrectomy, n = 7) with an incidence of
      5.4% (95% CI, 3.1-7.8%). All adrenal hematomas were located on the side of
      nephrectomy (right adrenal gland, n = 8; left adrenal gland, n = 11). In nine
      patients, the adrenal hematoma appeared as a round or oval lesion on
      postoperative imaging with a mean size of 2.6 cm (range, 1.5-4.0 cm). In 10
      patients, the adrenal hematoma appeared as diffuse enlargement of the adrenal
      gland on postoperative imaging with a mean thickness of 1.3 cm (range, 0.6-1.8
      cm). CONCLUSION: An adrenal hematoma was identified in 5.4% of patients on CT or
      MRI after nephrectomy. A new round or oval adrenal mass after nephrectomy should
      be differentiated from a metastasis.

PMID- 21098192
TI  - A diagnosis of cancer: understanding and empowering the patient.

PMID- 21098193
TI  - Patient size and radiation exposure in thoracic, pelvic, and abdominal CT
      examinations performed with automatic exposure control.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of patient
      size on the amount of radiation used to perform CT examinations of the chest,
      abdomen, and pelvis with automatic exposure control and on the corresponding
      patient doses. MATERIALS AND METHODS: Ninety-one patients underwent CT of the
      chest, abdomen, and pelvis with a 64-MDCT scanner with automatic exposure control
      in the x, y, and z planes (noise index, 11.5; tube rotation speed, 1 second;
      maximal x-ray tube capacity, 800 mA; slice thickness, 5 mm; slice interval, 5 mm;
      table speed, 40 mm/rotation; pitch, 1; tube voltage, 120 kVp). Volume CT dose
      index was obtained from the scanner console at the completion of each
      examination. The volume CT dose index and a dosimetry calculator were used to
      determine the organ dose in a 70-kg patient. Patient organ doses were obtained by
      correction of the calculator organ doses by factors that accounted for size
      variations in the lung and abdomen among patients and the corresponding regions
      in the phantom. RESULTS: The average volume CT dose index for a 60-kg patient was
      approximately 11 mGy, which increased to approximately 22 mGy for an 80-kg
      patient and to approximately 33 mGy for a 100-kg patient. The corresponding
      average liver doses for 60-kg patients was approximately 16 mGy, which increased
      to approximately 25 mGy for 80-kg patients and to approximately 34 mGy for 100-kg
      patients. For this patient cohort, the median doses to the colon, stomach, and
      liver were approximately 25 mGy; to the bladder, 31 mGy; and to the red bone
      marrow, 16 mGy. The 90th percentile organ doses were generally three to four
      times that of the corresponding 10th percentile organ doses. CONCLUSION: For body
      CT examinations performed with automatic exposure control, the radiation used to
      perform examinations of 100-kg patients is approximately three times that for a
      60-kg patient and results in organ doses that are generally twice as high as
      those in a 60-kg patient.

PMID- 21098195
TI  - MRI features of skeletal muscle lymphoma.
AB  - OBJECTIVE: The purpose of this study was to assess the MRI findings of skeletal
      muscle lymphoma. MATERIALS AND METHODS: MR images of pathologically proven
      lymphoma of skeletal muscle in 20 patients were retrospectively reviewed for the
      presence or absence of individual imaging findings. Nine patients had primary
      muscle lymphoma, and 11 patients had muscle metastasis from systemic lymphoma.
      RESULTS: The initial manifestation of skeletal muscle lymphoma was a muscle mass
      in 15 patients (75%) and abnormal muscle signal intensity in five patients (25%).
      Muscle enlargement was found in all cases. Long segmental involvement with
      orientation of the tumor along muscle fascicles was found in 15 patients (75%).
      Seventeen patients (85%) had traversing vessels within involved muscles. All of
      the tumors had equal to slightly increased signal intensity compared with normal
      muscle on T1-weighted images and intermediate signal intensity compared with fat
      on T2-weighted images. Among the 19 patients who underwent contrast-enhanced
      imaging, skeletal muscle lymphoma exhibited diffuse homogeneous enhancement in 13
      patients (68%), predominantly peripheral thick bandlike enhancement in four
      patients (21%), and marginal septal enhancement in two patients (11%). Thick
      irregular enhancement of both deep and superficial fascia was found in 16
      patients (84%), and one patient (5%) had deep enhancement only. Subcutaneous
      stranding was found in 16 patients (80%) and skin thickening in four patients
      (20%). CONCLUSION: Skeletal muscle lymphoma has distinctive MRI features that
      help differentiate it from other soft-tissue tumors and tumorlike lesions.

PMID- 21098194
TI  - Absorbed radiation dose in radiosensitive organs during coronary CT angiography
      using 320-MDCT: effect of maximum tube voltage and heart rate variations.
AB  - OBJECTIVE: The purpose of this article is to estimate the absorbed radiation dose
      in radiosensitive organs during coronary MDCT angiography using 320-MDCT and to
      determine the effects of tube voltage variation and heart rate (HR) control on
      absorbed radiation dose. MATERIALS AND METHODS: Semiconductor field effect
      transistor detectors were used to measure absorbed radiation doses for the
      thyroid, midbreast, breast, and midlung in an anthropomorphic phantom at 100,
      120, and 135 kVp at two different HRs of 60 and 75 beats per minute (bpm) with a
      scan field of view of 320 mm, 400 mA, 320 * 0.5 mm detectors, and 160 mm
      collimator width (160 mm range). The paired Student's t test was used for data
      evaluation. RESULTS: At 60 bpm, absorbed radiation doses for 100, 120, and 135
      kVp were 13.41 +/- 3.59, 21.7 +/- 4.12, and 29.28 +/- 5.17 mGy, respectively, for
      midbreast; 11.76 +/- 0.58, 18.86 +/- 1.06, and 24.82 +/- 1.45 mGy, respectively,
      for breast; 12.19 +/- 2.59, 19.09 +/- 3.12, and 26.48 +/- 5.0 mGy, respectively,
      for lung; and 0.37 +/- 0.14, 0.69 +/- 0.14, and 0.92 +/- 0.2 mGy, respectively,
      for thyroid. Corresponding absorbed radiation doses for 75 bpm were 38.34 +/-
      2.02, 59.72 +/- 3.13, and 77.8 +/- 3.67 mGy for midbreast; 26.2 +/- 1.74, 44 +/-
      1.11, and 52.84 +/- 4.07 mGy for breast; 38.02 +/- 1.58, 58.89 +/- 1.68, and 78
      +/- 2.93 mGy for lung; and 0.79 +/- 0.233, 1.04 +/- 0.18, and 2.24 +/- 0.52 mGy
      for thyroid. Absorbed radiation dose changes were significant for all organs for
      both tube voltage reductions as well as for HR control from 75 to 60 bpm at all
      tube voltage settings (p < 0.05). The absorbed radiation doses for the calcium
      score protocol were 11.2 +/- 1.4 mGy for midbreast, 9.12 +/- 0.48 mGy for breast,
      10.36 +/- 1.3 mGy for lung, and 0.4 +/- 0.05 mGy for thyroid. CONCLUSION: CT
      angiography with 320-MDCT scanners results in absorbed radiation doses in
      radiosensitive organs that compare favorably to those previously reported.
      Significant dose reductions can be achieved by tube voltage reductions and HR
      control.

PMID- 21098196
TI  - Temporal evolution of MRI findings after arthroscopic rotator cuff repair.
AB  - OBJECTIVE: The purpose of this article is to assess the changes occurring over
      time in the MRI appearance of repaired rotator cuff tendons and to correlate MRI
      appearance with clinical outcomes. SUBJECTS AND METHODS: MRI examinations were
      performed on 40 patients with full-thickness rotator cuff tears preoperatively
      and at 6 weeks, 3 months, and 12 months after arthroscopic repair. Preoperative
      scans were assessed for size of tear. Postoperative scans were evaluated for size
      of footprint, tendon thickness, signal intensity of the repaired tendon, and
      presence of full-thickness tear. Footprint and tendon thickness were graded from
      1 to 4 according to percentage of normal. Tendon signal intensity was graded from
      1 to 4 on the basis of the length of abnormal tendon. A composite score of
      footprint, tendon thickness, and tendon signal intensity was used to compare
      overall tendon appearance relative to the intact tendon. Rasch analysis was used
      to transform ordinal scale data into interval scale data. Using interval scale
      data, MRI findings were correlated to shoulder strength and the Constant-Murley
      score of clinical outcome. RESULTS: Four recurrent tendon tears occurred during
      the first postoperative year. Tendons appeared most disorganized compared with
      native tendon 3 months after surgery. Twenty-four of 36 intact tendons showed a
      decreased tendon score between 6 weeks and 3 months. There was considerable
      variability in tendon appearance among patients. There was no correlation between
      MRI appearance and clinical outcome score. CONCLUSION: MRI appearance of the
      repaired tendon changes over time but does not correlate with function or predict
      clinical outcomes at 1 year after surgery.

PMID- 21098197
TI  - Superolateral Hoffa's fat pad edema: association with patellofemoral maltracking
      and impingement.
AB  - OBJECTIVE: Nonelderly patients presenting with knee pain often have
      patellofemoral maltracking or impingement abnormalities. There is a relative
      paucity of literature on the incidence and significance of impingement-related
      edema of the superolateral aspect of Hoffa's (infrapatellar) fat pad in these
      cases. Our study was designed to systematically evaluate the correlation of
      superolateral Hoffa's fat pad edema with various anatomic parameters of trochlear
      morphology and patellar alignment. MATERIALS AND METHODS: We evaluated 50 knee
      MRI examinations in 47 patients for the presence of edema in superolateral
      Hoffa's fat pad and associated anatomic abnormalities of the patellofemoral
      joint. RESULTS: Of the 50 examinations, 25 (50%) showed superolateral Hoffa's fat
      pad edema, and statistically significant differences were seen between those with
      and without edema with respect to sex (6/22 men vs 19/28 women) and patellar
      tendon patellar-length ratio (1.3 +/- 0.16 and 1.1 +/- 0.12 for those with and
      without edema, respectively). CONCLUSION: The findings in our study suggest that
      edema in superolateral Hoffa's fat pad may be an important indicator of
      underlying patellofemoral maltracking or impingement in younger, symptomatic
      patients.

PMID- 21098198
TI  - Neuroimaging findings in alcohol-related encephalopathies.
AB  - OBJECTIVE: Our aim was to review the emergent neuroimaging findings of alcohol
      related CNS nontraumatic disorders. Alcohol (ethanol) promotes inflammatory
      processes, increases DNA damage, and creates oxidative stress. In addition, the
      accompanying thiamine deficiency may lead to Wernicke encephalopathy. Associated
      changes in serum osmolarity may lead to acute demyelination. CONCLUSION: Alcohol
      related encephalopathies can be life-threatening conditions but can be prevented
      or treated, if recognized.

PMID- 21098199
TI  - Cystic parathyroid adenoma: sonographic features and correlation with 99mTc
      sestamibi SPECT findings.
AB  - OBJECTIVE: The purpose of this study was to describe the typical ultrasound
      features of cystic parathyroid adenoma. MATERIALS AND METHODS: A review of a
      surgical database and electronic medical records from 2006 to 2009 identified the
      cases of 15 patients who underwent preoperative cervical sonography for primary
      hyperparathyroidism with subsequent resection of pathologically proven
      parathyroid adenoma with predominantly cystic components. Two radiologists
      retrospectively evaluated the preoperative ultrasound images and assessed for
      cyst complexity, size, location, and color Doppler vascularity. Technetium-99m
      sestamibi SPECT findings, surgical and pathologic reports, and the results of
      parathyroid hormone assay of the cyst fluid also were reviewed. RESULTS: Most of
      the cystic adenomas (14/15, 93%) were deep or inferolateral to the adjacent
      thyroid. The same percentage were elongated and had peripheral nodular
      components. An echogenic border separating the adenoma from the overlying thyroid
      was identified in 9 of 15 patients (60%). Color Doppler examination of 14
      patients showed feeding vessels with internal color flow to the solid components
      in 10 patients (71%). Six of 14 patients underwent preoperative or intraoperative
      sampling of cyst fluid, and the assay showed the parathyroid hormone levels
      ranged from 1,198 to greater than 5,000 pg/mL. Fourteen of 15 patients underwent
      preoperative sestamibi SPECT, and the adenoma was definitively localized in four
      patients (29%). The accuracy of preoperative localization improved to 79% (11/14)
      when sestamibi SPECT scans were interpreted in correlation with cervical
      ultrasound images. CONCLUSION: Awareness of typical sonographic features
      (location, color Doppler vascularity) may aid radiologists in preoperative
      localization of parathyroid adenomas, even when cystic degeneration occurs. In
      cases in which imaging or clinical features are equivocal, the results of cyst
      fluid sampling and parathyroid hormone assay are confirmatory.

PMID- 21098200
TI  - Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas.
AB  - OBJECTIVE: Atypical and anaplastic meningiomas have a greater likelihood of
      recurrence than benign meningiomas. The risk for recurrence is often estimated
      using the Ki-67 labeling index. The purpose of this study was to determine the
      correlation between Ki-67 and regional cerebral blood volume (rCBV) and between
      Ki-67 and apparent diffusion coefficient (ADC) in atypical and anaplastic
      meningiomas. MATERIALS AND METHODS: A retrospective review of the advanced
      imaging and immunohistochemical characteristics of atypical and anaplastic
      meningiomas was performed. The relative minimum ADC, relative maximum rCBV, and
      specimen Ki-67 index were measured. Pearson's correlation was used to compare
      these parameters. RESULTS: There were 23 cases with available ADC maps and 20
      cases with available rCBV maps. The average Ki-67 among the cases with ADC maps
      and rCBV maps was 17.6% (range, 5-38%) and 16.7% (range, 3-38%), respectively.
      The mean minimum ADC ratio was 0.91 (SD, 0.26) and the mean maximum rCBV ratio
      was 22.5 (SD, 7.9). There was a significant positive correlation between maximum
      rCBV and Ki-67 (Pearson's correlation, 0.69; p = 0.00038). However, there was no
      significant correlation between minimum ADC and Ki-67 (Pearson's correlation, 
      0.051; p = 0.70). CONCLUSION: Maximum rCBV correlated significantly with Ki-67 in
      high-grade meningiomas.

PMID- 21098201
TI  - 18F-FDG PET/CT of patients with cancer: comparison of whole-body and limited
      whole-body technique.
AB  - OBJECTIVE: Use of the routine field of view for whole-body (18)F-FDG PET/CT can
      lead to underestimation of the true extent of the disease because metastasis
      outside the typical base of skull to upper thigh field of view can be missed. The
      purpose of this study was to evaluate the incremental added value of true whole
      body as opposed to this limited whole-body PET/CT of cancer patients. MATERIALS
      AND METHODS: True whole-body FDG PET/CT, from the top of the skull to the bottom
      of the feet, was performed on 500 consecutively registered patients. A log was
      kept of cases of suspected malignancy outside the typical limited whole-body
      field of view. Suspected lesions in the brain, skull, and extremities were
      verified by correlation with surgical pathologic or clinical follow-up findings.
      RESULTS: Fifty-nine of 500 patients had PET/CT findings suggestive of malignancy
      outside the limited whole-body field of view. Thirty-one of those patients had
      known or suspected malignancy outside the limited whole-body field of view at the
      time of the true whole-body study. Among the other 28 patients, follow-up data
      were not available for two, six had false-positive findings, and new cancerous
      involvement was confirmed in 20. Detection of malignancy outside the limited
      whole-body field of view resulted in a change in management in 65% and in staging
      in 55% of the 20 cases. CONCLUSION: Our study showed that 20 of 500 (4.0%) of
      patients had previously unsuspected malignancy outside the typical limited whole
      body field of view. Detection of such malignancy resulted in a change in
      management in 13 of 500 cases (2.6%). We propose that adopting a true whole-body
      field of view in the imaging of cancer patients may lead to more accurate staging
      and restaging than achieved with the routinely used limited whole-body field of
      view.

PMID- 21098202
TI  - Impact of medication discontinuation on increased intestinal FDG accumulation in
      diabetic patients treated with metformin.
AB  - OBJECTIVE: We evaluated the impact of stopping medication for 2 days on
      reductions in the high intestinal FDG uptake induced by metformin. SUBJECTS AND
      METHODS: One hundred thirty-eight diabetic patients were divided into two groups:
      one in which the antihyperglycemic drug regimen included metformin (group A; n =
      107) and one in which the regimen did not include metformin (group B; n = 31).
      Fifty-two patients without diabetes mellitus served as the control group (group
      C). Group A was divided into two subgroups: 77 patients (group A1) were taking
      metformin at the time of FDG PET/CT scans, whereas the remaining 30 patients
      (group A2) were asked to stop taking metformin for 2 days before PET/CT scans. In
      addition, 10 diabetic patients underwent two consecutive PET/CT scans before and
      after the discontinuation of metformin. The intestinal FDG uptake and blood
      glucose levels were compared among the four groups, as well as before and after
      the discontinuation of metformin. RESULTS: The high intestinal FDG uptake in
      group A1 was significantly reduced after the discontinuation of metformin (p <
      0.001 vs group A2); thus, there were no significant differences among group A2,
      group B, and group C (p = 0.581-0.872). There were also no statistically
      significant differences in the blood glucose levels among the three groups of
      diabetic patients (p > 0.9). In 10 patients who underwent serial PET/CT scans,
      mean intestinal FDG uptake decreased by 64% without significant changes in the
      blood glucose level. Hidden colorectal malignancies were revealed in two patients
      after the discontinuation of medication. CONCLUSION: The discontinuation of
      metformin for 2 days is feasible for reducing the high intestinal FDG uptake
      induced by metformin.

PMID- 21098203
TI  - Cumulative effective dose associated with radiography and CT of adolescents with
      spinal injuries.
AB  - OBJECTIVE: The purpose of this study was to analyze the quantity and distribution
      of cumulative effective doses in diagnostic imaging of adolescents with spinal
      injuries. MATERIAL AND METHODS: At a level 1 trauma center from July 2003 through
      June 2009, imaging procedures during initial evaluation and hospitalization and
      after discharge of all patients 10-20 years old with spinal fractures were
      retrospectively analyzed. The cumulative effective doses for all imaging studies
      were calculated, and the doses to patients with spinal injuries who had multiple
      traumatic injuries were compared with the doses to patients with spinal injuries
      but without multiple injuries. The significance level was set at 5%. RESULTS:
      Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5
      years) entailed a median cumulative effective dose of 18.89 mSv. Patients with
      multiple injuries had a significantly higher total cumulative effective dose
      (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT
      related cumulative effective dose to multiple injury patients during the initial
      evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of
      the total cumulative effective dose. CONCLUSION: Adolescents with spinal injuries
      receive a cumulative effective dose equal to that of adult trauma patients and
      nearly three times that of pediatric trauma patients. Areas of focus in lowering
      cumulative effective dose should be appropriate initial estimation of trauma
      severity and careful selection of CT scan parameters.

PMID- 21098204
TI  - Percutaneous cryoablation of anterior renal masses: technique, efficacy, and
      safety.
AB  - OBJECTIVE: The safety and efficacy of renal tumor ablation are related, in part,
      to tumor location. Anterior tumors present a challenge due to the risk of injury
      to adjacent structures. The purpose of this study was to review the techniques,
      complications, and short-term outcomes of percutaneous cryoablation of anterior
      renal masses at a single institution. MATERIALS AND METHODS: We retrospectively
      identified the cases of 35 patients with 38 anterior renal masses managed with
      percutaneous imaging-guided cryoablation of renal tumors from March 2003 through
      February 2009. The technical success of the ablation procedure, serious
      complications, and evidence of local tumor recurrence were evaluated for each
      patient. RESULTS: The average maximal diameter of the anterior renal masses was
      2.9 cm (SD, 0.9 cm; range, 1.4-4.8 cm). A single cryoablation procedure was
      performed for treatment of each patient, and technically successful ablation was
      achieved for all 38 tumors. A single severe adverse event occurred in one of the
      35 patients (3% major complication rate). This patient had a pulmonary embolism
      (diagnosed at CT angiography the day after ablation). He recovered and was
      discharged from the hospital with anticoagulant medication only 2 days after the
      procedure. No local tumor recurrence was identified in any of the 29 patients who
      underwent follow-up contrast-enhanced CT or MRI with images available for review
      3 months or longer from the time of ablation (mean, 18 months; range, 3-45
      months). CONCLUSION: Percutaneous cryoablation of anterior renal masses can be
      performed with high technical success and low complication rates. The lack of
      local renal tumor recurrence at short-term follow-up evaluation in this study is
      encouraging, but long-term follow-up is necessary to ensure the durability of
      treatment.

PMID- 21098205
TI  - High-resolution 3D unenhanced ECG-gated respiratory-navigated MR angiography of
      the renal arteries: comparison with contrast-enhanced MR angiography.
AB  - OBJECTIVE: The aim of this study is to determine the diagnostic value of high
      resolution 3D unenhanced ECG-gated respiratory-navigated MR angiography (MRA) of
      the renal arteries using a steady-state free precession (SSFP) technique in
      comparison with 1.0-molar contrast-enhanced MRA in patients with suspected renal
      artery stenosis. SUBJECTS AND METHODS: Forty-five consecutive patients underwent
      unenhanced MRA before contrast-enhanced MRA within the same session. We assessed
      examination time, image quality, renal artery architecture, and localization and
      severity of renal artery stenosis. RESULTS: Examination time was shorter for
      contrast-enhanced MRA (mean +/- SD, 12 +/- 3 minutes) than for unenhanced MRA (19
      +/- 3 minutes; p < 0.001). On a 5-point scale, the image quality was similar for
      contrast-enhanced MRA (3.8 +/- 1.0) and unenhanced MRA (4.0 +/- 1.3; p = 0.24).
      Contrast-enhanced MRA offered more assessable data sets than did unenhanced MRA
      (95% vs 90%); however, unenhanced MRA had more data sets with maximum image
      quality (49% vs 30%). There was moderate agreement in stenosis grading between
      both MRA techniques (kappa = 0.51; p < 0.001), but in only one case (1.3%) we
      found mismatch of more than one severity stenosis grade (stenoses > 75%).
      Sensitivity, specificity, and positive and negative predictive values of
      unenhanced MRA to detect renal artery stenoses greater than 50% were 75%, 99%,
      75%, and 99%, respectively. CONCLUSION: We show that SSFP 3D unenhanced MRA is a
      very promising technique for patients with suspected renovascular disease and
      could be used as an alternative if gadolinium-based contrast agents cannot be
      administered.

PMID- 21098206
TI  - 13-year follow-up of a prospective comparison of the long-term clinical efficacy
      of temporary self-expanding metallic stents and pneumatic dilatation for the
      treatment of achalasia in 120 patients.
AB  - OBJECTIVE: The purpose of this article is to compare the efficacy of self
      expanding metallic stents and pneumatic dilation for the long-term clinical
      treatment of achalasia. SUBJECTS AND METHODS: Patients diagnosed with achalasia
      (n = 120) were allocated for treatment with pneumatic dilation (n = 30; group A)
      or a temporary self-expanding metallic stent with a diameter of 20 mm (n = 30;
      group B), 25 mm (n = 30; group C), or 30 mm (n = 30; group D). Data on clinical
      symptoms, complications, and long-term clinical outcomes were collected, and
      follow-up was performed at 6 months and at 1, 3-5, 5-8, 8-10, and more than 10
      years after surgery. RESULTS: Pneumatic dilation and stent placement were
      technically successful in all patients. The follow-up at more than 10 years
      revealed that the clinical remission rate in group D (83.3%) was higher than that
      in groups A (0%), B (0%), and C (28.6%), and the overall cumulative clinical
      failure rate in group D (13%) was lower than that in groups A (76.7%), B (53.3%),
      and C (26.7%). Patients in group D exhibited reduced dysphagia scores and lower
      esophageal sphincter pressures and had normal levels of barium height and width
      during the follow-up periods, whereas these markers increased with time in the
      other groups. The duration of primary patency in group D was also longer than
      that in groups A, B, and C. CONCLUSION: A temporary self-expanding metallic stent
      with a diameter of 30 mm has superior clinical efficacy for the treatment of
      achalasia compared with pneumatic dilation or self-expanding metallic stents with
      diameters of 20 or 25 mm.

PMID- 21098208
TI  - Fresh blood imaging of the peripheral vasculature: an emerging unenhanced MR
      technique.
AB  - OBJECTIVE: There is an increasing demand for MR angiography (MRA) techniques that
      do not require the administration of exogenous contrast material. Fresh blood
      imaging utilizes an ECG-gated fast spin-echo sequence to acquire images in both
      the systolic and diastolic phases of the cardiac cycle. Fast systolic arterial
      flow is differentiated from slower diastolic flow and a subtraction technique is
      used to produce angiographic images. We describe the technical aspects of
      performing lower extremity MRA and illustrate some sample cases. CONCLUSION:
      Fresh blood imaging is an emerging unenhanced MRA technique that has recently
      become commercially available. Early clinical trials appear promising and it is
      anticipated that fresh blood imaging will become invaluable, particularly in
      patients with impaired renal function. Technical refinements are still required
      to perfect this novel MR application, particularly for the assessment of distal
      calf and pedal vessels and for the evaluation of patients with arrhythmias and
      those with impaired cardiac function.

PMID- 21098207
TI  - Can Doppler sonography discern between hemodynamically significant and
      insignificant portal vein stenosis after adult liver transplantation?
AB  - OBJECTIVE: The purpose of our study was to determine whether Doppler sonography,
      using a strict reference standard, can specifically identify hemodynamically
      significant portal vein anastomotic stenosis after liver transplantation in
      adults. MATERIALS AND METHODS: The duplex and color Doppler examinations of 13
      consecutive adult patients who underwent portal venography for suspected portal
      vein stenosis after liver transplantation were retrospectively examined. Peak
      systolic velocity (PSV) and change in PSV (DeltaPSV) along the portal vein were
      correlated with portal venography. Stenoses above 50% on the basis of strict
      venographic criteria were considered hemodynamically significant. The Doppler
      studies before and after intervention were also assessed. Fourteen randomly
      chosen subjects with transplants without suspicion of portal anastomotic stenosis
      acted as controls. RESULTS: Six patients had significant portal vein stenosis (>
      50%) and seven had stenosis below 50%. PSV and DeltaPSV were significantly
      greater for patients with > 50% stenosis in comparison with those with <= 50%
      stenosis and control subjects. Optimal threshold values for PSV and DeltaPSV were
      80 and 60 cm/s, respectively, with either value alone yielding sensitivity of
      100% and specificity of 84% for significant stenosis. Threshold values also
      included cases of stenosis below 50%. Five of six patients with > 50% stenosis
      underwent stenting, with poststent PSV and DeltaPSV significantly declining to
      match that of control subjects. Three of seven with stenosis below 50% had stents
      placed but no significant change in the Doppler examination. CONCLUSION: Doppler
      threshold criteria reliably exclude those without posttransplantation portal vein
      stenosis and have high sensitivity for detecting portal stenosis. However, these
      criteria cannot discern the extent of stenosis.

PMID- 21098209
TI  - Tumors and pseudotumors of the secondary mullerian system: review with emphasis
      on cross-sectional imaging findings.
AB  - OBJECTIVE: Microscopic structures lined by mullerian epithelium are frequently
      seen outside the uterus and fallopian tubes and are termed "mullerian rests" or
      "secondary mullerian system." Varied entities ranging from benign endosalpingosis
      to highly malignant ovarian tumors are thought to be derived from the secondary
      mullerian system. Cross-sectional imaging findings of diseases and disorders of
      the secondary mullerian system are presented here. CONCLUSION: Familiarity with a
      wide spectrum of diseases and disorders of the secondary mullerian system allows
      accurate diagnosis and management.

PMID- 21098210
TI  - Computer-aided analysis of ultrasound elasticity images for classification of
      benign and malignant breast masses.
AB  - OBJECTIVE: The purpose of this study was to evaluate computer-aided analysis of
      ultrasound elasticity images for the classification of benign and malignant
      breast tumors. MATERIALS AND METHODS: Real-time ultrasound elastography of 140
      women (mean age, 46 years; age range, 35-67 years) with nonpalpable breast masses
      (101 benign and 39 malignant lesions) was performed before needle biopsy. A
      region of interest (ROI) was drawn around the margin of the mass, and a score for
      each pixel was assigned; scores ranged from 0 for the greatest strain to 255 for
      no strain. The diagnostic performances of a neural network based on the values of
      the six elasticity features were compared with visual assessment of elasticity
      images and BI-RADS assessment using B-mode images. RESULTS: The values for the
      area under the receiver operating characteristic curve (A(z)) of the six
      elasticity features--mean hue histogram value, skewness, kurtosis, difference
      histogram variation, edge density, and run length--were 0.84, 0.69, 0.63, 0.75,
      0.68, and 0.71, respectively. The sensitivity, specificity, positive predictive
      value, and negative predictive value of the neural network based on all six
      features were 92% (36/39), 74% (75/101), 58% (36/62), and 96% (75/78),
      respectively, with an A(z) value of 0.89, which is significantly higher than the
      A(z) of 0.81 for visual assessment by radiologists (p = 0.01) and 0.76 for BI
      RADS assessment using B-mode images (p = 0.002). CONCLUSION: Computer-aided
      analysis of ultrasound elasticity images has the potential to aid in the
      classification of benign and malignant breast tumors.

PMID- 21098211
TI  - BI-RADS descriptors for mammographically detected microcalcifications verified by
      histopathology after needle-localized open breast biopsy.
AB  - OBJECTIVE: The objective of our study was to retrospectively determine the
      positive predictive value of each descriptor and of combined descriptors for
      microcalcifications to predict the risk of malignancy as well as the appropriate
      final assessment category. MATERIALS AND METHODS: A total of 308 needle-localized
      open breast biopsies for mammographically detected microcalcifications were
      performed in 295 women (age range, 33-71 years; mean age, 52 years) during 7
      years. Thirteen patients had bilateral microcalcifications that were studied
      separately. Two breast radiologists retrospectively reviewed the
      microcalcifications with regard to their morphology, distribution, and extent and
      to associated findings and final assessment category, after which they
      categorized them into nine combined descriptors. Surgical pathology served as the
      reference standard for malignant lesions and follow-up of at least 12 months
      served as the reference for benign lesions. The Fisher's exact test, including
      odds ratios, was used for statistical analysis. RESULTS: Of the 308 needle
      localized open breast biopsies, 144 (47%) were malignant and 164 (53%) were
      benign. For combined descriptors of morphology and distribution, the odds ratios
      of malignancy regarding the higher probability of malignancy and ductal
      distribution were as follows: 0 for typically benign morphology or scattered
      distribution, 93.00 for intermediate concern and regional, 33.53 for intermediate
      concern and clustered, 5.00 for intermediate concern and ductal, 24.00 for higher
      probability of malignancy and regional, and 1.13 for higher probability of
      malignancy and clustered. CONCLUSION: Each descriptor and combined descriptors
      for microcalcifications and the final assessment category could help to predict
      the risk of malignancy.

PMID- 21098212
TI  - Targeted ultrasound in women younger than 30 years with focal breast signs or
      symptoms: outcomes analyses and management implications.
AB  - OBJECTIVE: The purpose of this article is to assess the accuracy of targeted
      breast ultrasound in women younger than 30 years presenting with focal breast
      signs or symptoms. MATERIALS AND METHODS: Retrospective review of the electronic
      medical records identified all ultrasound examinations from January 1, 2002,
      through August 30, 2006, performed for focal breast signs or symptoms in women
      younger than 30 years. BI-RADS assessments were recorded. Outcomes were
      determined by biopsy, 24 months of ultrasound surveillance, and linkage with the
      regional tumor registry. The overall cancer yield, sensitivity, specificity,
      negative predictive value (NPV), positive predictive value (PPV) 2, and PPV3 of
      ultrasound were calculated. RESULTS: Among 830 study patients, lesions were
      assessed as BI-RADS category 1 or 2 in 526 (63.4%), BI-RADS category 3 in 140
      (16.9%), BI-RADS category 4 in 163 (19.6%), and BI-RADS category 5 in one (0.1%)
      patient. Three malignancies were detected, for a cancer yield of 0.4%. No BI-RADS
      category 3 lesions, two BI-RADS category 4 lesions, and the single BI-RADS
      category 5 lesion were malignant. Ultrasound sensitivity was 100%, specificity
      was 80.5%, NPV was 100%, PPV2 was 1.8%, and PPV3 was 1.9%. CONCLUSION: Women
      younger than 30 years with focal breast signs or symptoms have a very low (0.4%)
      incidence of malignancy. The 100% sensitivity and NPV of targeted ultrasound in
      our study substantiates its use as an accurate primary imaging test in this
      clinical setting. We found no malignancies in BI-RADS category 3 lesions,
      supporting ultrasound surveillance over biopsy in this patient population.

PMID- 21098213
TI  - Effects of adult attachment and emotional distractors on brain mechanisms of
      cognitive control.
AB  - Using data from 34 participants who completed an emotion-word Stroop task during
      functional magnetic resonance imaging, we examined the effects of adult
      attachment on neural activity associated with top-down cognitive control in the
      presence of emotional distractors. Individuals with lower levels of secure-base
      script knowledge--reflected in an adult's inability to generate narratives in
      which attachment-related threats are recognized, competent help is provided, and
      the problem is resolved--demonstrated more activity in prefrontal cortical
      regions associated with emotion regulation (e.g., right orbitofrontal cortex) and
      with top-down cognitive control (left dorsolateral prefrontal cortex, anterior
      cingulate cortex, and superior frontal gyrus). Less efficient performance and
      related increases in brain activity suggest that insecure attachment involves a
      vulnerability to distraction by attachment-relevant emotional information and
      that greater cognitive control is required to attend to task-relevant,
      nonemotional information. These results contribute to the understanding of
      mechanisms through which attachment-related experiences may influence
      developmental adaptation.

PMID- 21098214
TI  - The rate of in vitro maturation of primary follicles from adult mice and the
      quality of oocytes is improved in the absence of anti-mullerian hormone.
AB  - Anti-Mullerian hormone (AMH) inhibits the recruitment of primordial follicles
      into the growing pool, but its role in primary and secondary follicles is not
      clear. We isolated primary follicles from the ovaries of 9- to 10-week old mice
      and examined whether AMH affected follicular development. Follicles were matured
      in media that was prepared using unsexed fetal bovine serum (FBS) or female FBS
      (FFBS) with or without added AMH for approximately 2 weeks and maturation rates
      to secondary follicles and metaphase II (MII) oocytes were measured by standard
      morphological criteria. Rates of parthenogenetic activation and in vitro
      fertilization (IVF) were assessed by cleavage and blastocyst development,
      respectively. Whereas addition of AMH blocked primary to secondary follicle
      transition, the primary to secondary and secondary to MII follicle maturation
      rates was significantly improved with FFBS. Folliculogenesis resumed once AMH was
      removed from the media of the arrested primary follicles. The rates of IVF and
      parthenogenesis of oocytes after in vitro maturation (IVM) without AMH were also
      improved compared to controls. The results indicate that removal of AMH from
      culture conditions during IVM from primary follicular stages should be considered
      to improve outcome.

PMID- 21098215
TI  - Variation in hyaluronan-binding protein 2 (HABP2) promoter region is associated
      with unexplained female infertility.
AB  - We set up to analyze polymorphisms in hyaluronan-binding protein 2 (HABP2) gene
      in healthy fertile women (n = 158) and in women with unexplained infertility (n =
      116) and to investigate the potential role of HABP2 in receptive endometrium.
      Minor rs1157916 A and the major rs2240879 A alleles together with AA genotypes
      were significantly less frequent in infertile women than in controls.
      Immunohistochemistry analysis of endometrial HABP2 expression at the time of
      implantation identified significantly lower HABP2 protein level in infertile
      women in stroma and vessels than in fertile women. Migration assay analysis of
      cultured trophoblast and endothelial cells toward HABP2 protein referred to the
      function of HABP2 in endometrial endothelial cells. In conclusion, our results
      indicate that polymorphisms in the regulatory region of HABP2 gene could
      influence gene expression levels in the receptive endometrium and could thereby
      be one reason for infertility complications in women with unexplained
      infertility. Additionally, HABP2 protein involvement in endometrial angiogenesis
      is proposed.

PMID- 21098217
TI  - The measurement of vesical detrusor electromyographic activity during nerve
      sparing radical hysterectomy.
AB  - OBJECTIVE: To evaluate the feasibility for confirming the preservation of the
      parasymphathetic nerve pathway innervating the bladder during nerve-sparing
      radical hysterectomy (RH). METHODS: A total of 20 patients underwent nerve
      sparing RH. Intraoperative electrical stimulation (IES) were performed on the
      root of pelvic splanchnic nerve (PSN) trunk while recording the electromyographic
      (EMG) activity of the vesical detrusor. The average duration achieving residual
      urine <=50 mL and urodynamic study (UDS) was observed. RESULTS: Evoked potentials
      were recorded when stimulating, in 18 patients who were referred IES-positive.
      Its duration was 9.89 days. The UDS results indicated that all voided normally.
      The remaining 2 IES-negative cases with no evoked potentials had longer duration
      and the micturitions were performed using abdominal pressure. CONCLUSION: During
      nerve-sparing RH, IES based on the measurement of EMG activity is a useful tool
      for confirmation of the preservation of parasymphathetic nerve pathway
      innervating the bladder and prediction of the postoperative bladder function.

PMID- 21098218
TI  - CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly
      improves survival during influenza infection.
AB  - Infection with influenza virus induces severe pulmonary immune pathology that
      leads to substantial human mortality. Although antiviral therapy is effective in
      preventing infection, no current therapy can prevent or treat influenza-induced
      lung injury. Previously, we reported that influenza-induced pulmonary immune
      pathology is mediated by inflammatory monocytes trafficking to virus-infected
      lungs via CCR2 and that influenza-induced morbidity and mortality are reduced in
      CCR2-deficient mice. In this study, we evaluated the effect of pharmacologically
      blocking CCR2 with a small molecule inhibitor (PF-04178903) on the entry of
      monocytes into lungs and subsequent morbidity and mortality in influenza-infected
      mice. Subcutaneous injection of mice with PF-04178903 was initiated 1 d prior to
      infection with influenza strain H1N1A/Puerto Rico/8/34. Compared with vehicle
      controls, PF-04178903-treated mice demonstrated a marked reduction in mortality
      (75 versus 0%) and had significant reductions in weight loss and hypothermia
      during subsequent influenza infection. Drug-treated mice also displayed
      significant reductions in bronchoalveolar lavage fluid total protein, albumin,
      and lactose dehydrogenase activity. Administration of PF-04178903 did not alter
      viral titers, severity of secondary bacteria infections (Streptococcus
      pneumoniae), or levels of anti-influenza-neutralizing Abs. Drug-treated mice
      displayed an increase in influenza nucleoprotein-specific cytotoxic T cell
      activity. Our results suggest that CCR2 antagonists may represent an effective
      prophylaxis against influenza-induced pulmonary immune pathology.

PMID- 21098220
TI  - Negative feedback regulation of NF-kappaB action by CITED2 in the nucleus.
AB  - NF-kappaB is a family of important transcription factors that modulate immunity,
      development, inflammation, and cancer. The biological activity of NF-kappaB is
      subjected to various spatial and temporal regulations. Bioinformatics analysis
      predicts that CITED2 is topologically close to NF-kappaB in the protein
      interaction networks. In this study, we show that ectopic expression or knockdown
      of CITED2 attenuates or potentiates, respectively, the expression of NF-kappaB
      responsive genes. Mechanistically, CITED2 constitutively localizes inside the
      nucleus and interacts specifically with the coactivator p300. This prevents p65
      from binding to p300, impairs p65 acetylation, and attenuates p65 binding to its
      cognate promoters. Furthermore, LPS induces CITED2 expression via NF-kappaB in
      macrophages. CITED2 sensitizes cells to TNF-alpha-induced apoptosis.
      Collectively, this study identifies CITED2 as a novel regulator of NF-kappaB in
      the nucleus, which reveals a negative feedback mechanism for NF-kappaB signaling.

PMID- 21098219
TI  - Graft-versus-host disease is independent of innate signaling pathways triggered
      by pathogens in host hematopoietic cells.
AB  - Graft-versus-host disease (GVHD) is initiated by APCs that prime alloreactive
      donor T cells. In antipathogen responses, Ag-bearing APCs receive signals through
      pattern-recognition receptors, including TLRs, which induce the expression of
      costimulatory molecules and production of inflammatory cytokines, which in turn
      mold the adaptive T cell response. However, in allogeneic hematopoietic stem cell
      transplantation (alloSCT), there is no specific pathogen, alloantigen is
      ubiquitous, and signals that induce APC maturation are undefined. To investigate
      APC activation in GVHD, we used recipient mice with hematopoietic cells
      genetically deficient in pathways critical for APC maturation in models in which
      host APCs are absolutely required. Strikingly, CD8-mediated and CD4-mediated GVHD
      were similar whether host APCs were wild-type or deficient in MyD88, TRIF, or
      MyD88 and TRIF, which excludes essential roles for TLRs and IL-1beta, the key
      product of inflammasome activation. Th1 differentiation was if anything augmented
      when APCs were MyD88/TRIF(-/-), and T cell production of IFN-gamma did not
      require host IL-12. GVHD was also intact when APCs lacked the type I IFNR, which
      amplifies APC activation pathways that induce type I IFNs. Thus in GVHD,
      alloreactive T cells can be activated when pathways critical for antipathogen T
      cell responses are impaired.

PMID- 21098221
TI  - A role for IL-15 in the migration of effector CD8 T cells to the lung airways
      following influenza infection.
AB  - The cytokines generated locally in response to infection play an important role
      in CD8 T cell trafficking, survival, and effector function, rendering these
      signals prime candidates for immune intervention. In this paper, we show that
      localized increases in the homeostatic cytokine IL-15 induced by influenza
      infection is responsible for the migration of CD8 effector T cells to the site of
      infection. Moreover, intranasal delivery of IL-15-IL-15Ralpha soluble complexes
      (IL-15c) specifically restores the frequency of effector T cells lost in the lung
      airways of IL-15-deficient animals after influenza infection. Exogenous IL-15c
      quantitatively augments the respiratory CD8 T cell response, and continued
      administration of IL-15c throughout the contraction phase of the anti-influenza
      CD8 T cell response magnifies the resultant CD8 T cell memory generated in situ.
      This treatment extends the ability of these cells to protect against heterologous
      infection, immunity that typically depreciates over time. Overall, our studies
      describe what to our knowledge is a new function for IL-15 in attracting effector
      CD8 T cells to the lung airways and suggest that adjuvanting IL-15 could be used
      to prolong anti-influenza CD8 T cell responses at mucosal surfaces to facilitate
      pathogen elimination.

PMID- 21098222
TI  - Mast cell-derived IL-10 suppresses germinal center formation by affecting T
      follicular helper cell function.
AB  - The most prevalent cancer diagnosed in the world is sunlight-induced skin cancer.
      In addition to being a complete carcinogen, UV radiation, the causative agent of
      skin cancer, induces immune suppression. Because UV-induced immune suppression is
      a well-recognized risk factor for skin cancer induction, it is crucial to
      understand the mechanisms underlying UV-induced immune suppression. Mast cells,
      which have recently emerged as immune regulatory cells, are particularly
      important in UV-induced immune suppression. UV exposure does not induce immune
      suppression in mast cell-deficient mice. We report that UV irradiation blocks
      germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell
      function, in part by altering the expression of transcription factors BCL-6 and
      BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab
      secretion was observed in UV-irradiated mast cell-deficient (Kit(W-sh/W-sh))
      mice. When mast cell-deficient mice were reconstituted with wild type mast cells,
      immune suppression was restored. Reconstituting the mast cell-deficient mice with
      bone marrow-derived mast cells from IL-10-deficient mice failed to restore the
      ability of UV radiation to suppress GC formation. Our findings demonstrate a
      function for mast cells, suppression of Tfh cell production, GC formation, and Ab
      production in vivo.

PMID- 21098223
TI  - TLR4 through IFN-beta promotes low molecular mass hyaluronan-induced neutrophil
      apoptosis.
AB  - Intratracheal administration of low molecular mass (LMM) hyaluronan (200 kDa)
      results in greater neutrophil infiltration in the lungs of TLR4(-/-) mice
      compared with that in wild-type mice. In general, enhanced neutrophil
      infiltration in tissue is due to cell influx; however, neutrophil apoptosis also
      plays an important role. We have assessed the effects of TLR4 in the regulation
      of neutrophil apoptosis in response to administration of LMM hyaluronan. We found
      that apoptosis of inflammatory neutrophils is impaired in TLR4(-/-) mice, an
      effect that depends upon the IFN-beta-mediated TRAIL/TRAILR system. IFN-beta
      levels were decreased in LMM hyaluronan-treated TLR4-deficient neutrophils. The
      treatment of inflammatory neutrophils with IFN-beta enhanced the levels of TRAIL
      and TRAILR 2. LMM hyaluronan-induced inflammatory neutrophil apoptosis was
      substantially prevented by anti-TRAIL neutralizing mAb. We conclude that
      decreased IFN-beta levels decrease the activity of the TRAIL/TRAILR system in
      TLR4-deficient neutrophils, leading to impaired apoptosis of neutrophils and
      resulting in abnormal accumulation of neutrophils in the lungs of LMM hyaluronan
      treated mice. Thus, TLR4 plays a novel homeostatic role in noninfectious lung
      inflammation by accelerating the elimination of inflammatory neutrophils.

PMID- 21098224
TI  - Nonconventional CD8+ T cell responses to Listeria infection in mice lacking MHC
      class Ia and H2-M3.
AB  - CD8(+) T cells restricted to MHC class Ib molecules other than H2-M3 have been
      shown to recognize bacterial Ags. However, the contribution of these T cells to
      immune responses against bacterial infection is not well defined. To investigate
      the immune potential of MHC class Ib-restricted CD8(+) T cells, we have generated
      mice that lack both MHC class Ia and H2-M3 molecules (K(b-/-)D (b-/-)M3(-/-)).
      The CD8(+) T cells present in K(b-/-)D (b-/-)M3(-/-) mice display an activated
      surface phenotype and are able to secrete IFN-gamma rapidly upon anti-CD3 and
      anti-CD28 stimulation. Although the CD8(+) T cell population is reduced in K(b-/
      )D (b-/-)M3(-/-) mice compared with that in K(b-/-)D (b-/-) mice, this population
      retains the capacity to expand significantly in response to primary infection
      with the bacteria Listeria monocytogenes. However, K(b-/-)D (b-/-)M3(-/-) CD8(+)
      T cells do not expand upon secondary infection, similar to what has been observed
      for H2-M3-restricted T cells. CD8(+) T cells isolated from Listeria-infected K(b
      /-)D (b-/-)M3(-/-) mice exhibit cytotoxicity and secrete proinflammatory
      cytokines in response to Listeria-infected APCs. These T cells are protective
      against primary Listeria infection, as Listeria-infected K(b-/-)D (b-/-)M3(-/-)
      mice exhibit reduced bacterial burden compared with that of infected beta(2)
      microglobulin-deficient mice that lack MHC class Ib-restricted CD8(+) T cells
      altogether. In addition, adoptive transfer of Listeria-experienced K(b-/-)D (b-/
      )M3(-/-) splenocytes protects recipient mice against subsequent Listeria
      infection in a CD8(+) T cell-dependent manner. These data demonstrate that other
      MHC class Ib-restricted CD8(+) T cells, in addition to H2-M3-restricted T cells,
      contribute to antilisterial immunity and may contribute to immune responses
      against other intracellular bacteria.

PMID- 21098225
TI  - A marked reduction in priming of cytotoxic CD8+ T cells mediated by stress
      induced glucocorticoids involves multiple deficiencies in cross-presentation by
      dendritic cells.
AB  - Protracted psychological stress elevates circulating glucocorticoids, which can
      suppress CD8(+) T cell-mediated immunity, but the mechanisms are incompletely
      understood. Dendritic cells (DCs), required for initiating CTL responses, are
      vulnerable to stress/corticosterone, which can contribute to diminished CTL
      responses. Cross-priming of CD8(+) T cells by DCs is required for initiating CTL
      responses against many intracellular pathogens that do not infect DCs. We
      examined the effects of stress/corticosterone on MHC class I (MHC I) cross
      presentation and priming and show that stress/corticosterone-exposed DCs have a
      reduced ability to cross-present OVA and activate MHC I-OVA(257-264)-specific T
      cells. Using a murine model of psychological stress and OVA-loaded beta(2)
      microglobulin knockout "donor" cells that cannot present Ag, DCs from stressed
      mice induced markedly less Ag-specific CTL proliferation in a glucocorticoid
      receptor-dependent manner, and endogenous in vivo T cell cytolytic activity
      generated by cross-presented Ag was greatly diminished. These deficits in cross
      presentation/priming were not due to altered Ag donation, Ag uptake
      (phagocytosis, receptor-mediated endocytosis, or fluid-phase uptake), or
      costimulatory molecule expression by DCs. However, proteasome activity in
      corticosterone-treated DCs or splenic DCs from stressed mice was partially
      suppressed, which limits formation of antigenic peptide-MHC I complexes. In
      addition, the lymphoid tissue-resident CD11b(-)CD24(+)CD8alpha(+) DC subset,
      which carries out cross-presentation/priming, was preferentially depleted in
      stressed mice. At the same time, CD11b(-)CD24(+)CD8alpha(-) DC precursors were
      increased, suggesting a block in development of CD8alpha(+) DCs. Therefore,
      glucocorticoid-induced changes in both the cellular composition of the immune
      system and intracellular protein degradation contribute to impaired CTL priming
      in stressed mice.

PMID- 21098226
TI  - A major role for Bim in regulatory T cell homeostasis.
AB  - We have previously shown that regulatory T cells (Treg) accumulate dramatically
      in aged animals and negatively impact the ability to control persistent
      infection. However, the mechanisms underlying the age-dependent accrual of Treg
      remain unclear. In this study, we show that Treg accumulation with age is
      progressive and likely not the result of increased thymic output, increased
      peripheral proliferation, or from enhanced peripheral conversion. Instead, we
      found that Treg from aged mice are more resistant to apoptosis than Treg from
      young mice. Although Treg from aged mice had increased expression of functional
      IL-7Ralpha, we found that IL-7R signaling was not required for maintenance of
      Treg in vivo. Notably, aged Treg exhibit decreased expression of the proapoptotic
      molecule Bim compared with Treg from young mice. Furthermore, in the absence of
      Bim, Treg accumulate rapidly, accounting for >25% of the CD4(+) T cell
      compartment by 6 mo of age. Additionally, accumulation of Treg in Bim-deficient
      mice occurred after the cells left the transitional recent thymic emigrant
      compartment. Mechanistically, we show that IL-2 drives preferential proliferation
      and accumulation of Bim(lo) Treg. Collectively, our data suggest that chronic
      stimulation by IL-2 leads to preferential expansion of Treg having low expression
      of Bim, which favors their survival and accumulation in aged hosts.

PMID- 21098227
TI  - Phosphatidylinositol 3-kinase activation attenuates the TLR2-mediated macrophage
      proinflammatory cytokine response to Francisella tularensis live vaccine strain.
AB  - An inadequate innate immune response appears to contribute to the virulence of
      Francisella tularensis following pulmonary infection. Studies in mice suggest
      that this poor response results from suppression of proinflammatory cytokine
      production early during infection, but the mechanisms involved are not
      understood. PI3K is known to regulate proinflammatory cytokine expression, but
      its exact role (positive versus negative) is controversial. We sought to clarify
      the role of PI3K in regulating proinflammatory signaling and cytokine production
      during infection with F. tularensis live vaccine strain (LVS). In this study, we
      demonstrate that the induction of TNF and IL-6 expression by LVS in mouse bone
      marrow-derived macrophages was markedly enhanced when PI3K activity was inhibited
      by either of the well-known chemical inhibitors, wortmannin or LY294002. The
      enhanced cytokine expression was accompanied by enhanced activation of p38 MAPK
      and ERK1/2, both of which were critical for LVS-induced expression of TNF and IL
      6. LVS-induced MAPK activation and cytokine production were TLR2- and MyD88-
      dependent. PI3K/Akt activation was MyD88-dependent, but was surprisingly TLR2
      independent. LVS infection also rapidly induced MAPK phosphatase-1 (MKP-1)
      expression; PI3K and TLR2 signaling were required. Peak levels of MKP-1
      correlated closely with the decline in p38 MAPK and ERK1/2 phosphorylation. These
      data suggest that infection by LVS restrains the TLR2-triggered proinflammatory
      response via parallel activation of PI3K, leading to enhanced MKP-1 expression,
      accelerated deactivation of MAPKs, and suppression of proinflammatory cytokine
      production. This TLR2-independent inhibitory pathway may be an important
      mechanism by which Francisella suppresses the host's innate immune response.

PMID- 21098229
TI  - A novel mechanism of rapid nuclear neutrophil extracellular trap formation in
      response to Staphylococcus aureus.
AB  - Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial
      molecules that constitute a newly described killing mechanism in innate immune
      defense. Previous publications reported that NETs take up to 3-4 h to form via an
      oxidant-dependent event that requires lytic death of neutrophils. In this study,
      we describe neutrophils responding uniquely to Staphylococcus aureus via a novel
      process of NET formation that did not require neutrophil lysis or even breach of
      the plasma membrane. The multilobular nucleus rapidly became rounded and
      condensed. During this process, we observed the separation of the inner and outer
      nuclear membranes and budding of vesicles, and the separated membranes and
      vesicles were filled with nuclear DNA. The vesicles were extruded intact into the
      extracellular space where they ruptured, and the chromatin was released. This
      entire process occurred via a unique, very rapid (5-60 min), oxidant-independent
      mechanism. Mitochondrial DNA constituted very little if any of these NETs. They
      did have a limited amount of proteolytic activity and were able to kill S.
      aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm
      presumably for later lytic NET production, but this was distinct from the
      vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase
      were identified in supernatants with NET-inducing activity, but Panton-Valentine
      leukocidin was the dominant NET inducer. We describe a new mechanism of NET
      release that is very rapid and contributes to trapping and killing of S. aureus.

PMID- 21098228
TI  - Neutrophils activate alveolar macrophages by producing caspase-6-mediated
      cleavage of IL-1 receptor-associated kinase-M.
AB  - Alveolar macrophages (AMs) are exposed to respirable microbial particles. Similar
      to phagocytes in the gastrointestinal tract, AMs can suppress inflammation after
      exposure to nonpathogenic organisms. IL-1R-associated kinase-M (IRAK-M) is one
      inhibitor of innate immunity, normally suppressing pulmonary inflammation. During
      pneumonia, polymorphonuclear neutrophils (PMNs) are recruited by chemotactic
      factors released by AMs to produce an intense inflammation. We report that intact
      IRAK-M is strongly expressed in resting human AMs but is cleaved in patients with
      pneumonia via PMN-mediated induction of caspase-6 (CASP-6) activity. PMN contact
      is necessary and PMN membranes are sufficient for CASP-6 induction in
      macrophages. PMNs fail to induce TNF-alpha fully in macrophages expressing CASP-6
      cleavage-resistant IRAK-M. Without CASP-6 expression, PMN stimulation fails to
      cleave IRAK-M, degrade IkappaBalpha, or induce TNF-alpha. CASP-6(-/-) mice
      subjected to cecal ligation and puncture have impaired TNF-alpha production in
      the lung and decreased mortality. LPS did not induce or require CASP-6 activity
      demonstrating that TLR2/4 signaling is independent from the CASP-6 regulated
      pathway. These data define a central role for CASP-6 in PMN-driven macrophage
      activation and identify IRAK-M as an important target for CASP-6. PMNs de-repress
      AMs via CASP-6-mediated IRAK-M cleavage. This regulatory system will blunt lung
      inflammation unless PMNs infiltrate the alveolar spaces.

PMID- 21098230
TI  - IL-17- and IFN-gamma-secreting Foxp3+ T cells infiltrate the target tissue in
      experimental autoimmunity.
AB  - CD4(+)Foxp3(+) regulatory T cells (Tregs) have been considered crucial in
      controlling immune system homeostasis, and their derangement is often associated
      to autoimmunity. Tregs identification is, however, difficult because most
      markers, including CD25 and Foxp3, are shared by recently activated T cells. We
      show in this paper that CD4(+)Foxp3(+) T cells are generated in peripheral
      lymphoid organs on immunization and readily accumulate in the target organ of an
      autoimmune reaction, together with classical inflammatory cells, constituting up
      to 50% of infiltrating CD4(+) T cells. Most CD4(+)Foxp3(+) T cells are, however,
      CD25(-) and express proinflammatory cytokines such as IL-17 and IFN-gamma,
      questioning their suppressive nature. Moreover, in vitro CD4(+) T lymphocytes
      from naive and autoimmune mice, stimulated to differentiate into Th1, Th2, Th17,
      and induced Tregs, display early mixed expression of lineage-specific markers.
      These results clearly point to an unprecedented plasticity of naive CD4(+) T
      cells, that integrating inflammatory signals may change their fate from the
      initial lineage commitment to a different functional phenotype.

PMID- 21098231
TI  - beta5 integrin is the major contributor to the alphaVintegrin-mediated blockade
      of HIV-1 replication.
AB  - Monocytes and macrophages are targets of HIV-1 infection and play critical roles
      in multiple aspects of viral pathogenesis. During the differentiation of
      monocytes to macrophages, adhesion molecules such as integrins are upregulated;
      therefore, they provide signals that control the process and subsequently may
      render macrophages more susceptible to HIV-1 infection. Previous work
      demonstrated that blocking alpha(v)-containing integrins triggered a signal
      transduction pathway leading to the inhibition of NF-kappaB-dependent HIV-1
      transcription. In this paper, we show the influence of the different alpha(v)
      coupled beta integrins in HIV-1 replication in macrophages. Inhibition of beta
      integrins, either by specific mAbs, small arginine-glycine-aspartic acid (RGD)
      mimetic compounds, or RNA interference, showed that integrin beta(5) was the
      major contributor to the integrin-mediated blockade of HIV-1 replication.
      Importantly, such inhibition did not induce changes in cell adhesion to the
      substrate. In conclusion, our results reveal a significant role of the integrin
      dimer alpha(v)beta(5) in HIV-1 infection of macrophages.

PMID- 21098232
TI  - Enhancing blood-stage malaria subunit vaccine immunogenicity in rhesus macaques
      by combining adenovirus, poxvirus, and protein-in-adjuvant vaccines.
AB  - Protein-in-adjuvant formulations and viral-vectored vaccines encoding blood-stage
      malaria Ags have shown efficacy in rodent malaria models and in vitro assays
      against Plasmodium falciparum. Abs and CD4(+) T cell responses are associated
      with protective efficacy against blood-stage malaria, whereas CD8(+) T cells
      against some classical blood-stage Ags can also have a protective effect against
      liver-stage parasites. No subunit vaccine strategy alone has generated
      demonstrable high-level efficacy against blood-stage infection in clinical
      trials. The induction of high-level Ab responses, as well as potent T and B cell
      effector and memory populations, is likely to be essential to achieve immediate
      and sustained protective efficacy in humans. This study describes in detail the
      immunogenicity of vaccines against P. falciparum apical membrane Ag 1 in rhesus
      macaques (Macaca mulatta), including the chimpanzee adenovirus 63 (AdCh63), the
      poxvirus modified vaccinia virus Ankara (MVA), and protein vaccines formulated in
      Alhydrogel or CoVaccine HT adjuvants. AdCh63-MVA heterologous prime-boost
      immunization induces strong and long-lasting multifunctional CD8(+) and CD4(+) T
      cell responses that exhibit a central memory-like phenotype. Three-shot (AdCh63
      MVA-protein) or two-shot (AdCh63-protein) regimens induce memory B cells and high
      titer functional IgG responses that inhibit the growth of two divergent strains
      of P. falciparum in vitro. Prior immunization with adenoviral vectors of
      alternative human or simian serotype does not affect the immunogenicity of the
      AdCh63 apical membrane Ag 1 vaccine. These data encourage the further clinical
      development and coadministration of protein and viral vector vaccine platforms in
      an attempt to induce broad cellular and humoral immune responses against blood
      stage malaria Ags in humans.

PMID- 21098233
TI  - Leishmania inhibitor of serine peptidase 2 prevents TLR4 activation by neutrophil
      elastase promoting parasite survival in murine macrophages.
AB  - Leishmania major is a protozoan parasite that causes skin ulcerations in
      cutaneous leishmaniasis. In the mammalian host, the parasite resides in
      professional phagocytes and has evolved to avoid killing by macrophages. We
      identified L. major genes encoding inhibitors of serine peptidases (ISPs), which
      are orthologs of bacterial ecotins, and found that ISP2 inhibits trypsin-fold S1A
      family peptidases. In this study, we show that L. major mutants deficient in ISP2
      and ISP3 (Deltaisp2/3) trigger higher phagocytosis by macrophages through a
      combined action of the complement type 3 receptor, TLR4, and unregulated activity
      of neutrophil elastase (NE), leading to parasite killing. Whereas all three
      components are required to mediate enhanced parasite uptake, only TLR4 and NE are
      necessary to promote parasite killing postinfection. We found that the production
      of superoxide by macrophages in the absence of ISP2 is the main mechanism
      controlling the intracellular infection. Furthermore, we show that NE modulates
      macrophage infection in vivo, and that the lack of ISP leads to reduced parasite
      burdens at later stages of the infection. Our findings support the hypothesis
      that ISPs function to prevent the activation of TLR4 by NE during the Leishmania
      macrophage interaction to promote parasite survival and growth.

PMID- 21098234
TI  - Evolutional conservation of molecular structure and antiviral function of a viral
      RNA receptor, LGP2, in Japanese flounder, Paralichthys olivaceus.
AB  - LGP2 is an important intracellular receptor that recognizes viral RNAs in innate
      immunity. To understand the mechanism of viral RNA recognition, we cloned an LGP2
      cDNA and gene in Japanese flounder (Paralichthys olivaceus). Viral hemorrhagic
      septicemia virus-induced expressions of LGP2 mRNA were evaluated in vivo and in
      vitro by quantitative real-time PCR (Q-PCR) using primers based on the clone
      sequences. The expression of LGP2 mRNA in the kidney dramatically increased at 3
      d postinfection. The expression of LGP2 mRNA also increased in the head kidney
      leukocytes stimulated with artificial dsRNA (polyinosin-polycytidylic acid) in
      vitro. To evaluate the antiviral activity of the flounder LGP2, three expression
      constructs containing pcDNA4-LGP2 (full-length), pcDNA4-LGP2DeltaRD (regulatory
      domain deleted), and pcDNA4-Empty (as a negative control) were transfected into
      the hirame (flounder) natural embryo (hirame natural embryo) cell line. Forty
      eight hours after transfection, the transfected cells were infected with ssRNA
      viruses, viral hemorrhagic septicemia virus, or hirame rhabdovirus. The
      cytopathic effects of the viruses were delayed by the overexpression of Japanese
      flounder LGP2. The Q-PCR demonstrated that mRNA expression levels of type I IFN
      and IFN-inducible genes (Mx and ISG15) in the hirame natural embryo cells
      overexpressing LGP2 were increased by polyinosin-polycytidylic acid and viral
      infections. These results suggest that Japanese flounder LGP2 plays an important
      role in the recognition of both viral ssRNA and dsRNA to induce the antiviral
      activity by the production of IFN-stimulated proteins.

PMID- 21098235
TI  - Netrin-1 signaling dampens inflammatory peritonitis.
AB  - Previous studies implicated the anti-inflammatory potential of the adenosine 2B
      receptor (A2BAR). A2BAR activation is achieved through adenosine, but this is
      limited by its very short t(1/2). To further define alternative adenosine
      signaling, we examined the role of netrin-1 during acute inflammatory
      peritonitis. In this article, we report that animals with endogenous repression
      of netrin-1 (Ntn1(+/-)) demonstrated increased cell count, increased peritoneal
      cytokine concentration, and pronounced histological changes compared with
      controls in a model of zymosan A peritonitis. Exogenous netrin-1 significantly
      decreased i.p. inflammatory changes. This effect was not present in animals with
      deletion of A2BAR (A2BAR(-/-)). A2BAR(-/-) animals demonstrated no change in cell
      count, i.p. cytokine concentration, or histology in response to netrin-1
      injection. These data strengthen the role of netrin-1 as an immunomodulatory
      protein exerting its function in dependence of the A2BAR and further define
      alternative adenosine receptor signaling.

PMID- 21098236
TI  - CD8+CD122+ regulatory T cells (Tregs) and CD4+ Tregs cooperatively prevent and
      cure CD4+ cell-induced colitis.
AB  - We identified CD8(+)CD122(+) regulatory T cells (Tregs) and demonstrated their
      importance in the maintenance of immune homeostasis and in the recovery from
      experimental autoimmune encephalomyelitis. In this paper, we show that
      CD8(+)CD122(+) Tregs effectively prevent and cure colitis in a mouse model. In
      our experiments, colitis was induced in lymphocyte-deficient RAG-2(-/-) mice by
      transferring CD4(+)CD45RB(high) cells that were excluded with CD4(+) Tregs.
      Cotransfer of CD8(+)CD122(+) cells clearly suppressed the development of colitis,
      and this suppressive effect was similar to that of CD4(+)CD45RB(low) cells that
      were mostly CD4(+) Tregs. CD8(+)CD122(+) cells obtained from IL-10(-/-) mice were
      unable to suppress colitis, indicating that IL-10 is an important effect
      transmitting factor in the suppression of colitis. CD8(+)CD122(+) cells showed a
      suppressive effect when they were transferred 4 wk after CD4(+)CD45RB(high)
      cells, indicating the therapeutic potential of CD8(+)CD122(+) cells. A mixture of
      CD8(+)CD122(+) cells and CD4(+)CD45RB(low) cells was far more effective than
      single Tregs, indicating the synergistic effect of these Tregs. These overall
      findings demonstrate the potential role of CD8(+) Tregs, and possibly together
      with CD4(+) Tregs, in the medical care of inflammatory bowel disease patients.

PMID- 21098237
TI  - A rapid, high-throughput viability assay for Blastocystis spp. reveals
      metronidazole resistance and extensive subtype-dependent variations in drug
      susceptibilities.
AB  - Blastocystis is an emerging protistan parasite of controversial pathogenesis.
      Although metronidazole (Mz) is standard therapy for Blastocystis infections,
      there have been accumulating reports of treatment failure, suggesting the
      existence of drug-resistant isolates. Furthermore, very little is known about
      Blastocystis susceptibility to standard antimicrobials. In the present study, we
      established resazurin and XTT viability microassays for Blastocystis spp.
      belonging to subtypes 4 and 7, both of which have been suggested to represent
      pathogenic zoonotic subtypes. The optimized resazurin assay was used to screen a
      total of 19 compounds against both subtypes. Interestingly, subtype 7 parasites
      were resistant to Mz, a 1-position-substituted 5-nitroimidazole (5-NI), while
      subtype 4 parasites were sensitive. Some cross-resistance was observed to
      tinidazole, another 1-position 5-NI. Conversely, subtype 4 parasites were
      resistant to emetine, while subtype 7 parasites were sensitive. Position 2 5-NIs
      were effective against both subtypes, as were ornidazole, nitazoxanide,
      furazolidone, mefloquine, quinicrine, quinine, cotrimoxazole (trimethoprim
      sulfamethoxazole), and iodoacetamide. Both subtypes were resistant to
      chloroquine, doxycycline, paromomycin, ampicillin, and pyrimethamine. This is the
      first study to report extensive variations in drug sensitivities among two
      clinically important subtypes. Our study highlights the need to reevaluate
      established treatment regimens for Blastocystis infections and offers clear new
      treatment options for Mz treatment failures.

PMID- 21098238
TI  - The in vitro contribution of autolysins to bacterial killing elicited by
      amoxicillin increases with inoculum size in Enterococcus faecalis.
AB  - The mechanisms of antibiotic-induced cell death are poorly understood despite the
      critical role of the bactericidal activities of antibiotics for successful
      treatment of severe infections. These mechanisms include irreversible damaging of
      macromolecules by reactive oxygen species and bacteriolysis mediated by
      peptidoglycan hydrolases (autolysins). We have assessed the contribution of the
      second mechanism by using an autolysin-deficient mutant of Enterococcus faecalis
      and shown that it contributes to amoxicillin-induced cell lysis only at a high
      bacterial density.

PMID- 21098239
TI  - ISAba825, a functional insertion sequence modulating genomic plasticity and
      bla(OXA-58) expression in Acinetobacter baumannii.
AB  - ISAba825, an insertion sequence found inactivating Acinetobacter baumannii carO,
      was tagged with a kanamycin (Kn) resistance cassette. ISAba825::Kn effectively
      transposed in A. baumannii, showing preference for short, AT-enriched target
      sequences, generating 6- to 9-bp target duplications. Additionally, we detected
      the presence of ISAba825 upstream of a plasmid-borne bla(OXA-58) gene, generating
      a hybrid promoter largely enhancing its expression and leading to carbapenem
      resistance. Overall, a role for ISAba825 in carbapenem resistance modulation in
      A. baumannii is proposed.

PMID- 21098240
TI  - The antibiotic monensin causes cell cycle disruption of Toxoplasma gondii
      mediated through the DNA repair enzyme TgMSH-1.
AB  - Monensin is a polyether ionophore antibiotic that is widely used in the control
      of coccidia in animals. Despite its significance in veterinary medicine, little
      is known about its mode of action and potential mechanisms of resistance in
      coccidian parasites. Here we show that monensin causes accumulation of the
      coccidian Toxoplasma gondii at an apparent late-S-phase cell cycle checkpoint. In
      addition, experiments utilizing a monensin-resistant T. gondii mutant show that
      this effect of monensin is dependent on the function of a mitochondrial homologue
      of the MutS DNA damage repair enzyme (TgMSH-1). Furthermore, the same TgMSH-1
      dependent cell cycle disruption is observed with the antiparasitic ionophore
      salinomycin and the DNA alkylating agent methyl nitrosourea. Our results suggest
      a novel mechanism for the mode of action of monensin and salinomycin on coccidial
      parasites, in which the drug activates an MSH-1-dependent cell cycle checkpoint
      by an unknown mechanism, ultimately leading to the death of the parasite. This
      model would indicate that cell cycle disruption is an important mediator of drug
      susceptibility and resistance to ionophoric antibiotics in coccidian parasites.

PMID- 21098241
TI  - Diversity of the early step of the futalosine pathway.
AB  - We recently demonstrated that the futalosine pathway was operating in some
      bacteria for the biosynthesis of menaquinone and that futalosine was converted
      into dehypoxanthinyl futalosine (DHFL) by an MqnB of Thermus thermophilus. In
      this study, we found that aminodeoxyfutalosine, which has adenine instead of
      hypoxanthine in futalosine, was directly converted into DHFL by an MqnB of
      Helicobacter pylori. Therefore, this step is potentially an attractive target for
      the development of specific anti-H. pylori drugs.

PMID- 21098243
TI  - Antibacterial action of polyphosphate on Porphyromonas gingivalis.
AB  - Polyphosphate [poly(P)] has antibacterial activity against various Gram-positive
      bacteria. In contrast, Gram-negative bacteria are generally resistant to poly(P).
      Here, we describe the antibacterial characterization of poly(P) against a Gram
      negative periodontopathogen, Porphyromonas gingivalis. The MICs of pyrophosphate
      (Na(4)P(2)O(7)) and all poly(P) (Na(n + 2)P(n)O(3n + 1); n = 3 to 75) tested for
      the bacterium by the agar dilution method were 0.24% and 0.06%, respectively.
      Orthophosphate (Na(2)HPO(4)) failed to inhibit bacterial growth. Poly-P75 was
      chosen for further study. In liquid medium, 0.03% poly-P75 was bactericidal
      against P. gingivalis irrespective of the growth phase and inoculum size, ranging
      from 10(5) to 10(9) cells/ml. UV-visible spectra of the pigments from P.
      gingivalis grown on blood agar with or without poly-P75 showed that poly-P75
      reduced the formation of MU-oxo bisheme by the bacterium. Poly-P75 increased
      hemin accumulation on the P. gingivalis surface and decreased energy-driven
      uptake of hemin by the bacterium. The expression of the genes encoding
      hemagglutinins, gingipains, hemin uptake loci, chromosome replication, and energy
      production was downregulated, while that of the genes related to iron storage and
      oxidative stress was upregulated by poly-P75. The transmission electron
      microscope showed morphologically atypical cells with electron-dense granules and
      condensed nucleoid in the cytoplasm. Collectively, poly(P) is bactericidal
      against P. gingivalis, in which hemin/heme utilization is disturbed and oxidative
      stress is increased by poly(P).

PMID- 21098244
TI  - Interaction of W-substituted analogs of cyclo-RRRWFW with bacterial
      lipopolysaccharides: the role of the aromatic cluster in antimicrobial activity.
AB  - The activity of cyclo-RRRWFW (c-WFW) against Escherichia coli has been shown to
      be modulated by the aromatic motif and the lipopolysaccharides (LPS) in the
      bacterial outer membrane. To identify interaction sites and to elucidate the mode
      of c-WFW action, peptides were synthesized by the replacement of tryptophan (W)
      with analogs having altered hydrophobicity, dipole and quadrupole moments,
      hydrogen-bonding ability, amphipathicity, and ring size. The peptide activity
      against Bacillus subtilis and erythrocytes increased with increasing
      hydrophobicity, whereas the effect on E. coli revealed a more complex pattern.
      Although they had no effect on the E. coli inner membrane even at concentrations
      higher than the MIC, peptides permeabilized the outer membrane according to their
      antimicrobial activity pattern, suggesting a major role of LPS in peptide
      transport across the wall. For isothermal titration calorimetry (ITC) studies of
      peptide-lipid bilayer interaction, we used POPC (1-palmitoyl-2-oleoyl-sn-glycero
      3-phospho-choline), either alone or in mixtures with 1-palmitoyl-2-oleoyl-sn
      glycero-3-[phospho-rac-(1-glycerol)] (POPG), to mimic the charge properties of
      eukaryotic and bacterial membranes, respectively, as well as in mixtures with
      lipid A, rough LPS, and smooth LPS as models of the outer membrane of E. coli.
      Peptide accumulation was determined by both electrostatic and hydrophobic
      interactions. The susceptibility of the lipid systems followed the order of POPC
      smooth LPS >> POPC-rough LPS > POPC-lipid A = POPC-POPG > POPC. Low peptide
      hydrophobicity and enhanced flexibility reduced binding. The influence of the
      other properties on the free energy of partitioning was low, but an enhanced
      hydrogen-bonding ability and dipole moment resulted in remarkable variations in
      the contribution of enthalpy and entropy. In the presence of rough and smooth
      LPS, the binding-modulating role of these parameters decreased. The highly
      differentiated activity pattern against E. coli was poorly reflected in peptide
      binding to LPS-containing membranes. However, stronger partitioning into POPC
      smooth LPS than into POPC-rough LPS uncovered a significant role of O-antigen and
      outer core oligosaccharides in peptide transport and the permeabilization of the
      outer membrane and the anti-E. coli activity of the cyclic peptides.

PMID- 21098242
TI  - Combinatorial phenotypic signatures distinguish persistent from resolving
      methicillin-resistant Staphylococcus aureus bacteremia isolates.
AB  - Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB)
      (positive blood cultures after >=7 days of therapy) represents a clinically
      challenging subset of invasive MRSA infections. In this investigation, we
      examined the potential correlation of specific virulence signatures with PB
      versus resolving MRSA bacteremia (RB) (negative blood cultures within 2 to 4 days
      of therapy) strains. Thirty-six MRSA isolates from patients enrolled in a recent
      multinational clinical trial were studied for (i) susceptibility to host defense
      cationic peptides (HDPs) (i.e., thrombin-induced platelet microbicidal proteins
      [tPMPs] and human neutrophil peptide 1 [hNP-1]); (ii) adherence to host
      endovascular ligands (fibronectin) and cells (endothelial cells); and (iii)
      biofilm formation. We found that PB isolates exhibited significantly reduced
      susceptibilities to tPMPs and hNP-1 (P < 0.001 and P = 0.023, respectively).
      There was no significant association between the PB outcome and fibronectin
      binding, endothelial cell binding, or biofilm formation (P = 0.25, 0.97, and
      0.064 versus RB strains, respectively). However, multiple logistic regression
      analysis revealed that the PB outcome was significantly associated with the
      combination of reduced susceptibilities to HDPs and extent of biofilm formation
      (P < 0.0001). Similar results were obtained in a second analysis using days of
      bacteremia as a continuous outcome, showing that reduced HDP susceptibilities and
      increased biofilm formation cocontributed to predict the duration of bacteremia.
      Our data indicate that PB isolates have specific pathogenic signatures
      independent of conventional antimicrobial susceptibility. These combinatorial
      mosaics can be defined and used to prospectively distinguish PB from RB strains
      in advance and potentially to predict ultimate clinical outcomes.

PMID- 21098245
TI  - Vancomycin bonded to bone grafts prevents bacterial colonization.
AB  - Infection is an important medical problem associated with the use of bone
      allografts. To retard bacterial colonization, we have recently reported on the
      modification of bone allografts with the antibiotic vancomycin (VAN). In this
      report, we examine the ability of this antibiotic-modified allograft to resist
      bacterial colonization and biofilm formation. When antibiotic was coupled to the
      allograft, a uniform distribution of the antibiotic was apparent. Following
      challenges with Staphylococcus aureus for 6 h, the covalently bonded VAN
      decreased colonization as a function of inoculum, ranging from 0.8 to 2.0 log(10)
      CFU. Furthermore, the VAN-modified surface resisted biofilm formation, even in
      topographical niches that provide a protected environment for bacterial adhesion.
      Attachment of the antibiotic to the allograft surface was robust, and the bonded
      VAN was stable whether incubated in aqueous media or in air, maintaining levels
      of 75 to 100% of initial levels over 60 days. While the VAN-modified allograft
      inhibited the Gram-positive S. aureus colonization, in keeping with VAN's
      spectrum of activity, the VAN-modified allograft was readily colonized by the
      Gram-negative Escherichia coli. Finally, initial toxicity measures indicated that
      the VAN-modified allograft did not influence osteoblast colonization or
      viability. Since the covalently tethered antibiotic is stable, is active, retains
      its specificity, and does not exhibit toxicity, it is concluded that this
      modified allograft holds great promise for decreasing bone graft-associated
      infections.

PMID- 21098246
TI  - In silico children and the glass mouse model: clinical trial simulations to
      identify and individualize optimal isoniazid doses in children with tuberculosis.
AB  - Children with tuberculosis present with high rates of disseminated disease and
      tuberculous (TB) meningitis due to poor cell-mediated immunity. Recommended
      isoniazid doses vary from 5 mg/kg/day to 15 mg/kg/day. Antimicrobial
      pharmacokinetic/pharmacodynamic studies have demonstrated that the ratio of the 0
      to 24-h area under the concentration-time curve (AUC(0-24)) to the MIC best
      explains isoniazid microbial kill. The AUC(0-24)/MIC ratio associated with 80% of
      maximal kill (80% effective concentration [EC(80)]), considered the optimal
      effect, is 287.2. Given the pharmacokinetics of isoniazid encountered in children
      10 years old or younger, with infants as a special group, and given the
      differences in penetration of isoniazid into phagocytic cells, epithelial lining
      fluid, and subarachnoid space during TB meningitis, we performed 10,000 patient
      Monte Carlo simulations to determine how well isoniazid doses of between 2.5 and
      40 mg/kg/day would achieve or exceed the EC(80). None of the doses examined
      achieved the EC(80) in >=90% of children. Doses of 5 mg/kg were universally
      inferior; doses of 10 to 15 mg/kg/day were adequate only under the very limited
      circumstances of children who were slow acetylators and had disease limited to
      pneumonia. Each of the three disease syndromes, acetylation phenotype, and being
      an infant required different doses to achieve adequate AUC(0-24)/MIC exposures in
      an acceptable proportion of children. We conclude that current recommended doses
      for children are likely suboptimal and that isoniazid doses in children are best
      individualized based on disease process, age, and acetylation status.

PMID- 21098247
TI  - Development and validation of a high-performance liquid chromatography method for
      determination of cefquinome concentrations in sheep plasma and its application to
      pharmacokinetic studies.
AB  - Cefquinome has a broad spectrum of antibacterial activity and was developed
      especially for use in animals. A simple and sensitive high-performance liquid
      chromatography (HPLC) method with UV-visible detection for quantification of
      cefquinome concentrations in sheep plasma was developed and validated. Separation
      of cefquinome from plasma components was achieved on a Phenomenex Gemini C(18)
      column (250 mm by 4.6 mm; internal diameter [i.d.], 5 MUm). The mobile phase
      consisted of acetonitrile and 0.1% trifluoroacetic acid in water and was
      delivered at a rate of 0.9 ml/min. A simple and rapid sample preparation involved
      the addition of methanol to 200 MUl of plasma to precipitate plasma proteins
      followed by direct injection of 50 MUl of supernatant into the high-performance
      liquid chromatography system. The linearity range of the proposed method was 0.02
      to 12 MUg/ml. The intraday and interday coefficients of variation obtained from
      cefquinome were less than 5%, and biases ranged from -3.76% to 1.24%. Mean
      recovery based on low-, medium-, and high-quality control standards ranged
      between 92.0 and 93.9%. Plasma samples were found to be stable in various storage
      conditions (freeze-thaw, postpreparative, short-term, and long-term stability).
      The method described was found to be readily available, practicable, cheap,
      rapid, sensitive, precise, and accurate. It was successfully applied to the study
      of the pharmacokinetics of cefquinome in sheep. This method can be very useful
      and an alternate to performing pharmacokinetic studies in the determination of
      cefquinome for clinical use.

PMID- 21098248
TI  - Whole-genome analysis of Salmonella enterica serovar Typhimurium T000240 reveals
      the acquisition of a genomic island involved in multidrug resistance via IS1
      derivatives on the chromosome.
AB  - Salmonella enterica serovar Typhimurium is frequently associated with life
      threatening systemic infections, and the recent global emergence of multidrug
      resistance in S. enterica isolates from agricultural and clinical settings has
      raised concerns. In this study, we determined the whole-genome sequence of
      fluoroquinolone-resistant S. enterica serovar Typhimurium T000240 strain (DT12)
      isolated from human gastroenteritis in 2000. Comparative genome analysis revealed
      that T000240 displays high sequence similarity to strain LT2, which was
      originally isolated in 1940, indicating that progeny of LT2 might be reemerging.
      T000240 possesses a unique 82-kb genomic island, designated as GI-DT12, which is
      composed of multidrug resistance determinants, including a Tn2670-like composite
      transposon (class 1 integron [intI1, bla(oxa-30), aadA1, qacEDelta1, and sul1],
      mercury resistance proteins, and chloramphenicol acetyltransferase), a Tn10-like
      tetracycline resistance protein (tetA), the aerobactin iron-acquisition
      siderophore system (lutA and lucABC), and an iron transporter (sitABCD). Since GI
      DT12 is flanked by IS1 derivatives, IS1-mediated recombination likely played a
      role in the acquisition of this genomic island through horizontal gene transfer.
      The aminoglycoside-(3)-N-acetyltransferase (aac(3)) gene and a class 1 integron
      harboring the dfrA1 gene cassette responsible for gentamicin and trimethoprim
      resistance, respectively, were identified on plasmid pSTMDT12_L and appeared to
      have been acquired through homologous recombination with IS26. This study
      represents the first characterization of the unique genomic island GI-DT12 that
      appears to be associated with possible IS1-mediated recombination in S. enterica
      serovar Typhimurium. It is expected that future whole-genome studies will aid in
      the characterization of the horizontal gene transfer events for the emerging S.
      enterica serovar Typhimurium strains.

PMID- 21098249
TI  - Molecular analysis of antimicrobial resistance mechanisms in Neisseria
      gonorrhoeae isolates from Ontario, Canada.
AB  - Surveillance of gonococcal antimicrobial resistance and the molecular
      characterization of the mechanisms underlying these resistance phenotypes are
      essential in order to establish correct empirical therapies, as well as to
      describe the emergence of new mechanisms in local bacterial populations. To
      address these goals, 149 isolates were collected over a 1-month period (October
      November 2008) at the Ontario Public Health Laboratory, Toronto, Canada, and
      susceptibility profiles (8 antibiotics) were examined. Mutations in previously
      identified targets or the presence of some enzymes related to resistance (r),
      nonsusceptibility (ns) (resistant plus intermediate categories), or reduced
      susceptibility (rs) to the antibiotics tested were also studied. A significant
      proportion of nonsusceptibility to penicillin (PEN) (89.2%), tetracycline (TET)
      (72.3%), ciprofloxacin (CIP) (29%), and macrolides (erythromycin [ERY] and
      azithromycin; 22.3%) was found in these strains. Multidrug resistance was
      observed in 18.8% of the collection. Although all the strains were susceptible to
      spectinomycin and extended-spectrum cephalosporins (ESC) (ceftriaxone and
      cefixime), 9.4% of them displayed reduced susceptibility to extended-spectrum
      cephalosporins. PBP 2 mosaic structures were found in all of these ESC(rs)
      isolates. Alterations in the mtrR promoter, MtrR repressor (TET(r), PEN(ns),
      ESC(rs), and ERY(ns)), porin PIB (TET(r) and PEN(ns)), and ribosomal protein S10
      (TET(r)) and double mutations in gyrA and parC quinolone resistance-determining
      regions (QRDRs) (CIP(r)) were associated with and presumably responsible for the
      resistance phenotypes observed. This is the first description of ESC(rs) in
      Canada. The detection of this phenotype indicates a change in the epidemiology of
      this resistance and highlights the importance of continued surveillance to
      preserve the last antimicrobial options available.

PMID- 21098250
TI  - Expression of multidrug efflux pump genes acrAB-tolC, mdfA, and norE in
      Escherichia coli clinical isolates as a function of fluoroquinolone and multidrug
      resistance.
AB  - In a single quantitative study, we measured acrA, acrB, tolC, mdfA, and norE
      expression in Escherichia coli clinical isolates by using real-time PCR. acrA and
      acrB overexpression strongly correlated with fluoroquinolone and multidrug
      resistance; tolC, mdfA, and norE expression did not. The order of abundance of
      efflux pump transcripts in all fluoroquinolone-susceptible isolates was tolC
      (highest), then acrA and acrB, and then mdfA and norE. Our findings suggest acrAB
      overexpression is an indicator of multidrug resistance.

PMID- 21098251
TI  - Use of inverse PCR for analysis of class 1 integrons carrying an unusual 3'
      conserved segment structure.
AB  - By using inverse PCR and DNA sequencing, 13 sul3-associated mutational integrons,
      2 defective class 1 integrons, and 1 qnrB2-associated complex sul1-type class 1
      integrons were identified in Salmonella enterica serovar Choleraesuis,
      Pseudomonas aeruginosa, and Enterobacter cloacae, respectively. In addition,
      conjugation and Southern hybridization demonstrated that unusual class 1
      integrons were located on plasmids or integrated into chromosomal DNA. Thus, an
      inverse PCR assay can be a valuable tool for the analysis of unusual structures
      of the 3' conserved region of class 1 integrons.

PMID- 21098252
TI  - A novel chimeric lysin shows superiority to mupirocin for skin decolonization of
      methicillin-resistant and -sensitive Staphylococcus aureus strains.
AB  - Staphylococcus aureus is a major human pathogen responsible for a number of
      serious and sometimes fatal infections. One of its reservoirs on the human body
      is the skin, which is known to be a source of invasive infection. The potential
      for an engineered staphylococcus-specific phage lysin (ClyS) to be used for
      topical decolonization is presented. We formulated ClyS into an ointment and
      applied it to a mouse model of skin colonization/infection with S. aureus. Unlike
      the standard topical antibacterial agent mupirocin, ClyS eradicated a
      significantly greater number of methicillin-susceptible S. aureus (MSSA) and 
      resistant S. aureus (MRSA) bacteria: a 3-log reduction with ClyS as opposed to a
      2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a
      decreased potential for the development of resistance by MRSA and MSSA organisms
      compared to that from the use of mupirocin in vitro. Because antibodies may
      affect enzyme function, we tested antibodies developed after repeated ClyS
      exposure for their effect on ClyS killing ability. Our results showed no
      inhibition of ClyS activity at various antibody titers. These data demonstrate
      the potential of developing ClyS as a novel class of topical antimicrobial agents
      specific to staphylococcus.

PMID- 21098253
TI  - Efficacy of fosfomycin in experimental osteomyelitis due to methicillin-resistant
      Staphylococcus aureus.
AB  - The activity of fosfomycin was evaluated in an experimental methicillin-resistant
      Staphylococcus aureus (MRSA) osteomyelitis model. Eighteen rats were treated for
      4 weeks with 150 mg of fosfomycin/kg of body weight intraperitoneally once daily
      or with saline placebo. After treatment, animals were euthanized and the infected
      tibiae were processed for quantitative bacterial culture. Bone cultures were
      positive for methicillin-resistant S. aureus in all 9 (100%) untreated controls
      and in 2 of 9 (22.2%) fosfomycin-treated rats. Thus, fosfomycin treatment was
      significantly more efficacious than placebo. No development of resistance was
      observed after the 4-week treatment period.

PMID- 21098254
TI  - In vitro antimicrobial activity of wall teichoic acid biosynthesis inhibitors
      against Staphylococcus aureus isolates.
AB  - Staphylococcus aureus is the leading cause of invasive and superficial human
      infections, is increasingly antibiotic resistant, and is therefore the target for
      the development of new antimicrobials. Compounds (1835F03 and targocil) were
      recently shown to function as bacteriostatic inhibitors of wall teichoic acid
      (WTA) biosynthesis in S. aureus. To assess the value of targeting WTA
      biosynthesis in human infection, it was therefore of interest to verify the
      involvement of WTA in bacterial binding to human corneal epithelial cells (HCECs)
      and to assess the activities of inhibitors of WTA biosynthesis against clinical
      isolates of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S.
      aureus (MRSA) from cases of human keratitis. The 1835F03 MIC(90)s were 8 MUg/ml
      for MSSA keratitis isolates and >32 MUg/ml for MRSA keratitis isolates. The
      MIC(90) for the analog of 1835F03, targocil, was 2 MUg/ml for both MRSA and MSSA.
      Targocil exhibited little toxicity at concentrations near the MIC, with increased
      toxicity occurring at higher concentrations and with longer exposure times.
      Targocil activity was moderately sensitive to the presence of serum, but it
      inhibited extracellular and intracellular bacteria in the presence of HCECs
      better than vancomycin. Targocil-resistant strains exhibited a significantly
      reduced ability to adhere to HCECs.

PMID- 21098255
TI  - Single-dose pharmacokinetics, safety, and tolerability of albinterferon alfa-2b
      in subjects with end-stage renal disease on hemodialysis compared to those in
      matched healthy volunteers.
AB  - Albinterferon alfa-2b (albIFN) is being developed, in combination with ribavirin,
      for the treatment of hepatitis C virus infection. This study was designed to
      evaluate the pharmacokinetics, safety, and tolerability of a 900-MUg dose of
      albIFN administered as a single subcutaneous injection in end-stage renal disease
      (ESRD) patients on hemodialysis and matched healthy volunteers (by age [+/-5
      years], weight [+/-5 kg], and gender). The maximum concentration in plasma
      (C(max)) and the area under the concentration-time curve from time zero to
      infinity (AUC(0-infinity)) were 42.8 +/- 14.0 ng/ml and 16,414 +/- 4,203 ng.h/ml,
      respectively, for healthy volunteers, while the C(max) and AUC(0-infinity) were
      49.9 +/- 20.9 ng/ml and 18,919 +/- 8,008 ng.h/ml, respectively, for ESRD
      patients. The geometric least-squares mean ratios were 1.15 (90% confidence
      interval [CI], 0.78, 1.68) for C(max) and 1.11 (90% CI, 0.83, 1.48) for AUC(0
      infinity). Adverse events were as expected for an interferon (e.g., flu-like
      symptoms), with the main laboratory adverse event being a decline in total white
      blood cell count, which was specifically related to a decline in the neutrophil
      count. This effect was somewhat greater in the ESRD patients, with the maximal
      decreases in neutrophil counts from those at the baseline being (-2.6 +/- 0.32) *
      10(9) and (-2.19 +/- 0.58) * 10(9) cells/liter for the ESRD patients and the
      healthy volunteers, respectively. This study indicates no significant effect of
      renal failure on the pharmacokinetics of albIFN. Safety and tolerability were as
      expected for an interferon.

PMID- 21098256
TI  - Complementarity-determining region 3 size spectratypes of T cell receptor beta
      chains in CD8+ T cells following antiviral treatment of chronic hepatitis B.
AB  - An increased CD8(+) T cell response to hepatitis B virus (HBV) peptides occurs
      between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B.
      It is not known whether these cells have antiviral function. The aim of this
      study was to determine whether clonal expansions of CD8(+) T cells at these time
      points predict the virological response to therapy. Peripheral blood CD8(+) T
      cells were obtained from 20 patients treated with lamivudine or telbivudine for
      chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of
      each T cell receptor (TCR) beta chain variable region (Vbeta) gene family was
      analyzed, and the changes in the numbers of Vbeta families with clonal expansions
      were compared in subjects with (n = 12) and without (n = 8) a virological
      response (52 week HBV DNA < 300 copies/ml). The number of CD8(+) TCR Vbeta
      families with clonal expansions at 12 weeks relative to baseline (median [10th to
      90th percentile], +2.5 [0 to +7] versus +1 [0 to +2], P = 0.03) and at 24 weeks
      relative to 12 weeks (+1 [0 to +2] versus -1 [-3 to +4], P = 0.006) was higher in
      subjects with a virological response versus subjects without a virological
      response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral
      blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P
      < 0.0001) in responders. Increased numbers of CD8(+) T cell expansions after
      antiviral therapy are associated with a virological response to treatment. These
      CD8(+) T cells are a potential target for a therapeutic vaccine for chronic
      hepatitis B.

PMID- 21098257
TI  - In silico investigation of intracranial blast mitigation with relevance to
      military traumatic brain injury.
AB  - Blast-induced traumatic brain injury is the most prevalent military injury in
      Iraq and Afghanistan, yet little is known about the mechanical effects of blasts
      on the human head, and still less is known about how personal protective
      equipment affects the brain's response to blasts. In this study we investigated
      the effect of the Advanced Combat Helmet (ACH) and a conceptual face shield on
      the propagation of stress waves within the brain tissue following blast events.
      We used a sophisticated computational framework for simulating coupled fluid
      solid dynamic interactions and a three-dimensional biofidelic finite element
      model of the human head and intracranial contents combined with a detailed model
      of the ACH and a conceptual face shield. Simulations were conducted in which the
      unhelmeted head, head with helmet, and head with helmet and face shield were
      exposed to a frontal blast wave with incident overpressure of 10 atm. Direct
      transmission of stress waves into the intracranial cavity was observed in the
      unprotected head and head with helmet simulations. Compared to the unhelmeted
      head, the head with helmet experienced slight mitigation of intracranial
      stresses. This suggests that the existing ACH does not significantly contribute
      to mitigating blast effects, but does not worsen them either. By contrast, the
      helmet and face shield combination impeded direct transmission of stress waves to
      the face, resulting in a delay in the transmission of stresses to the
      intracranial cavity and lower intracranial stresses. This suggests a possible
      strategy for mitigating blast waves often associated with military concussion.

PMID- 21098258
TI  - Mechanistic insights into cognate substrate discrimination during proofreading in
      translation.
AB  - Editing/proofreading by aminoacyl-tRNA synthetases is an important quality
      control step in the accurate translation of the genetic code that removes
      noncognate amino acids attached to tRNA. Defects in the process of editing result
      in disease conditions including neurodegeneration. While proofreading, the
      cognate amino acids larger by a methyl group are generally thought to be
      sterically rejected by the editing modules as envisaged by the "Double-Sieve
      Model." Strikingly using solution based direct binding studies, NMR-heteronuclear
      single quantum coherence (HSQC) and isothermal titration calorimetry experiments,
      with an editing domain of threonyl-tRNA synthetase, we show that the cognate
      substrate can gain access and bind to the editing pocket. High-resolution crystal
      structural analyses reveal that functional positioning of substrates rather than
      steric exclusion is the key for the mechanism of discrimination. A strategically
      positioned "catalytic water" molecule is excluded to avoid hydrolysis of the
      cognate substrate using a "RNA mediated substrate-assisted catalysis mechanism"
      at the editing site. The mechanistic proof of the critical role of RNA in
      proofreading activity is a completely unique solution to the problem of cognate
      noncognate selection mechanism.

PMID- 21098259
TI  - Structural identification of cation binding pockets in the plasma membrane proton
      pump.
AB  - The activity of P-type plasma membrane H(+)-ATPases is modulated by H(+) and
      cations, with K(+) and Ca(2+) being of physiological relevance. Using X-ray
      crystallography, we have located the binding site for Rb(+) as a K(+) congener,
      and for Tb(3+) and Ho(3+) as Ca(2+) congeners. Rb(+) is found coordinated by a
      conserved aspartate residue in the phosphorylation domain. A single Tb(3+) ion is
      identified positioned in the nucleotide-binding domain in close vicinity to the
      bound nucleotide. Ho(3+) ions are coordinated at two distinct sites within the
      H(+)-ATPase: One site is at the interface of the nucleotide-binding and
      phosphorylation domains, and the other is in the transmembrane domain toward the
      extracellular side. The identified binding sites are suggested to represent
      binding pockets for regulatory cations and a H(+) binding site for protons
      leaving the pump molecule. This implicates Ho(3+) as a novel chemical tool for
      identification of proton binding sites.

PMID- 21098260
TI  - Divalent counterion-induced condensation of triple-strand DNA.
AB  - Understanding and manipulation of the forces assembling DNA/RNA helices have
      broad implications for biology, medicine, and physics. One subject of
      significance is the attractive force between dsDNA mediated by polycations of
      valence >= 3. Despite extensive studies, the physical origin of the "like-charge
      attraction" remains unsettled among competing theories. Here we show that triple
      strand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by
      alkaline-earth divalent cations that are unable to condense dsDNA. We further
      show that our observation is general by examining several cations (Mg(2+),
      Ba(2+), and Ca(2+)) and two distinct tsDNA constructs. Cation-condensed tsDNA
      forms ordered hexagonal arrays that redissolve upon adding monovalent salts.
      Forces between tsDNA helices, measured by osmotic stress, follow the form of
      hydration forces observed with condensed dsDNA. Probing a well-defined system of
      point-like cations and tsDNAs with more evenly spaced helical charges, the
      counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is
      condensed by cations of lower valence provides new insights into theories of
      polyelectrolytes and the biological and pathological roles of tsDNA. Cations and
      tsDNAs also hold promise as a model system for future studies of DNA-DNA
      interactions and electrostatic interactions in general.

PMID- 21098261
TI  - Effects of Pleistocene glaciations and rivers on the population structure of
      Bornean orangutans (Pongo pygmaeus).
AB  - Sundaland, a tropical hotspot of biodiversity comprising Borneo and Sumatra among
      other islands, the Malay Peninsula, and a shallow sea, has been subject to
      dramatic environmental processes. Thus, it presents an ideal opportunity to
      investigate the role of environmental mechanisms in shaping species distribution
      and diversity. We investigated the population structure and underlying mechanisms
      of an insular endemic, the Bornean orangutan (Pongo pygmaeus). Phylogenetic
      reconstructions based on mtDNA sequences from 211 wild orangutans covering the
      entire range of the species indicate an unexpectedly recent common ancestor of
      Bornean orangutans 176 ka (95% highest posterior density, 72-322 ka), pointing to
      a Pleistocene refugium. High mtDNA differentiation among populations and rare
      haplotype sharing is consistent with a pattern of strong female philopatry. This
      is corroborated by isolation by distance tests, which show a significant
      correlation between mtDNA divergence and distance and a strong effect of rivers
      as barriers for female movement. Both frequency-based and Bayesian clustering
      analyses using as many as 25 nuclear microsatellite loci revealed a significant
      separation among all populations, as well as a small degree of male-mediated gene
      flow. This study highlights the unique effects of environmental and biological
      features on the evolutionary history of Bornean orangutans, a highly endangered
      species particularly vulnerable to future climate and anthropogenic change as an
      insular endemic.

PMID- 21098262
TI  - Deletion of hensin/DMBT1 blocks conversion of beta- to alpha-intercalated cells
      and induces distal renal tubular acidosis.
AB  - Acid-base transport in the renal collecting tubule is mediated by two canonical
      cell types: the beta-intercalated cell secretes HCO(3) by an apical Cl:HCO(3)
      named pendrin and a basolateral vacuolar (V)-ATPase. Acid secretion is mediated
      by the alpha-intercalated cell, which has an apical V-ATPase and a basolateral
      Cl:HCO(3) exchanger (kAE1). We previously suggested that the beta-cell converts
      to the alpha-cell in response to acid feeding, a process that depended on the
      secretion and deposition of an extracellular matrix protein termed hensin
      (DMBT1). Here, we show that deletion of hensin from intercalated cells results in
      the absence of typical alpha-intercalated cells and the consequent development of
      complete distal renal tubular acidosis (dRTA). Essentially all of the
      intercalated cells in the cortex of the mutant mice are canonical beta-type
      cells, with apical pendrin and basolateral or diffuse/bipolar V-ATPase. In the
      medulla, however, a previously undescribed cell type has been uncovered, which
      resembles the cortical beta-intercalated cell in ultrastructure, but does not
      express pendrin. Polymerization and deposition of hensin (in response to
      acidosis) requires the activation of beta1 integrin, and deletion of this gene
      from the intercalated cell caused a phenotype that was identical to the deletion
      of hensin itself, supporting its critical role in hensin function. Because
      previous studies suggested that the conversion of beta- to alpha-intercalated
      cells is a manifestation of terminal differentiation, the present results
      demonstrate that this differentiation proceeds from HCO(3) secreting to acid
      secreting phenotypes, a process that requires deposition of hensin in the ECM.

PMID- 21098264
TI  - Impacting our young.

PMID- 21098263
TI  - Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3
      signaling.
AB  - Many tumors contain heterogeneous populations of cells, only some of which
      exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence
      suggests that these aggressive cancer cells, often termed "cancer stem cells" or
      "cancer stem-like cells" (CSCs), rely upon developmental signaling pathways that
      are important for survival and expansion of normal stem cells. Here we report
      that, in analogy to embryonic mammary epithelial biology, estrogen signaling
      expands the pool of functional breast CSCs through a paracrine FGF/FGFR/Tbx3
      signaling pathway. Estrogen or FGF9 pretreatment induced CSC properties of breast
      cancer cell lines and freshly isolated breast cancer cells, whereas cotreatment
      of cells with tamoxifen or a small molecule inhibitor of FGFR signaling was
      sufficient to prevent the estrogen-induced expansion of CSCs. Furthermore,
      reduction of FGFR or Tbx3 gene expression was able to abrogate tumorsphere
      formation, whereas ectopic Tbx3 expression increased tumor seeding potential by
      100-fold. These findings demonstrate that breast CSCs are stimulated by estrogen
      through a signaling pathway that similarly controls normal mammary epithelial
      stem cell biology.

PMID- 21098265
TI  - A regulon conserved in monocot and dicot plants defines a functional module in
      antifungal plant immunity.
AB  - At least two components that modulate plant resistance against the fungal powdery
      mildew disease are ancient and have been conserved since the time of the monocot
      dicot split (~ 200 Mya). These components are the seven transmembrane domain
      containing MLO/MLO2 protein and the syntaxin ROR2/PEN1, which act
      antagonistically and have been identified in the monocot barley (Hordeum vulgare)
      and the dicot Arabidopsis thaliana, respectively. Additionally, syntaxin
      interacting N-ethylmaleimide sensitive factor adaptor protein receptor proteins
      (VAMP721/722 and SNAP33/34) as well as a myrosinase (PEN2) and an ABC transporter
      (PEN3) contribute to antifungal resistance in both barley and/or Arabidopsis.
      Here, we show that these genetically defined defense components share a similar
      set of coexpressed genes in the two plant species, comprising a statistically
      significant overrepresentation of gene products involved in regulation of
      transcription, posttranslational modification, and signaling. Most of the
      coexpressed Arabidopsis genes possess a common cis-regulatory element that may
      dictate their coordinated expression. We exploited gene coexpression to uncover
      numerous components in Arabidopsis involved in antifungal defense. Together, our
      data provide evidence for an evolutionarily conserved regulon composed of core
      components and clade/species-specific innovations that functions as a module in
      plant innate immunity.

PMID- 21098266
TI  - Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity.
AB  - In yeast, Sir2 family proteins (sirtuins) regulate gene silencing, recombination,
      DNA repair, and aging via histone deacetylation. Most of the seven mammalian
      sirtuins (Sirt1-Sirt7) have been implicated as NAD(+)-dependent protein
      deacetylases with targets ranging from transcriptional regulators to metabolic
      enzymes. We report that neural-specific deletion of sirtuin 6 (Sirt6) in mice
      leads to postnatal growth retardation due to somatotropic attenuation through low
      growth hormone (GH) and insulin-like growth factor 1 (IGF1) levels. However,
      unlike Sirt6 null mice, neural Sirt6-deleted mice do not die from hypoglycemia.
      Instead, over time, neural Sirt6-deleted mice reach normal size and ultimately
      become obese. Molecularly, Sirt6 deletion results in striking hyperacetylation of
      histone H3 lysine 9 (H3K9) and lysine 56 (H3K56), two chromatin marks implicated
      in the regulation of gene activity and chromatin structure, in various brain
      regions including those involved in neuroendocrine regulation. On the basis of
      these findings, we propose that Sirt6 functions as a central regulator of somatic
      growth and plays an important role in preventing obesity by modulating neural
      chromatin structure and gene activity.

PMID- 21098267
TI  - Simultaneous magnetic resonance imaging of ventilation distribution and gas
      uptake in the human lung using hyperpolarized xenon-129.
AB  - Despite a myriad of technical advances in medical imaging, as well as the growing
      need to address the global impact of pulmonary diseases, such as asthma and
      chronic obstructive pulmonary disease, on health and quality of life, it remains
      challenging to obtain in vivo regional depiction and quantification of the most
      basic physiological functions of the lung-gas delivery to the airspaces and gas
      uptake by the lung parenchyma and blood-in a manner suitable for routine
      application in humans. We report a method based on MRI of hyperpolarized xenon
      129 that permits simultaneous observation of the 3D distributions of ventilation
      (gas delivery) and gas uptake, as well as quantification of regional gas uptake
      based on the associated ventilation. Subjects with lung disease showed variations
      in gas uptake that differed from those in ventilation in many regions, suggesting
      that gas uptake as measured by this technique reflects such features as
      underlying pathological alterations of lung tissue or of local blood flow.
      Furthermore, the ratio of the signal associated with gas uptake to that
      associated with ventilation was substantially altered in subjects with lung
      disease compared with healthy subjects. This MRI-based method provides a way to
      quantify relationships among gas delivery, exchange, and transport, and appears
      to have significant potential to provide more insight into lung disease.

PMID- 21098268
TI  - Danish dementia mice suggest that loss of function and not the amyloid cascade
      causes synaptic plasticity and memory deficits.
AB  - According to the prevailing "amyloid cascade hypothesis," genetic dementias such
      as Alzheimer's disease and familial Danish dementia (FDD) are caused by amyloid
      deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive
      alterations. To efficiently reproduce amyloid lesions, murine models of human
      dementias invariably use transgenic expression systems. However, recent FDD
      transgenic models showed that Danish amyloidosis does not cause memory defects,
      suggesting that other mechanisms cause Danish dementia. We studied an animal
      knock-in model of FDD (FDD(KI/+)) genetically congruous with human cases.
      FDD(KI/+) mice present reduced Bri2 levels, impaired synaptic plasticity and
      severe hippocampal memory deficits. These animals show no cerebral lesions that
      are reputed characteristics of human dementia, such as tangles or amyloid
      plaques. Bri2(+/-) mice exhibit synaptic and memory deficits similar to FDD(KI/+)
      mice, and memory loss of FDD(KI/+) mice is prevented by expression of WT BRI2,
      indicating that Danish dementia is caused by loss of BRI2 function. Together, the
      data suggest that clinical dementia in Danish patients occurs via a loss of
      function mechanism and not as a result of amyloidosis and tauopathy.

PMID- 21098269
TI  - Modulation of postoperative cognitive decline via blockade of inflammatory
      cytokines outside the brain.

PMID- 21098270
TI  - Receptor interacting protein kinases mediate retinal detachment-induced
      photoreceptor necrosis and compensate for inhibition of apoptosis.
AB  - Apoptosis has been shown to be a significant form of cell loss in many diseases.
      Detachment of photoreceptors from the retinal pigment epithelium, as seen in
      various retinal disorders, causes photoreceptor loss and subsequent vision
      decline. Although caspase-dependent apoptotic pathways are activated after
      retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails
      to prevent photoreceptor death; thus, we investigated other pathways leading to
      cell loss. Here, we show that receptor interacting protein (RIP) kinase-mediated
      necrosis is a significant mode of photoreceptor cell loss in an experimental
      model of retinal detachment and when caspases are inhibited, RIP-mediated
      necrosis becomes the predominant form of death. RIP3 expression, a key activator
      of RIP1 kinase, increased more than 10-fold after retinal detachment.
      Morphological assessment of detached retinas treated with Z-VAD showed decreased
      apoptosis but significantly increased necrotic photoreceptor death. RIP1 kinase
      inhibitor necrostatin-1 or Rip3 deficiency substantially prevented those necrotic
      changes and reduced oxidative stress and mitochondrial release of apoptosis
      inducing factor. Thus, RIP kinase-mediated programmed necrosis is a redundant
      mechanism of photoreceptor death in addition to apoptosis, and simultaneous
      inhibition of RIP kinases and caspases is essential for effective neuroprotection
      and may be a novel therapeutic strategy for treatment of retinal disorders.

PMID- 21098271
TI  - Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia.
AB  - High hyperdiploid acute lymphoblastic leukemia (ALL) is one of the most common
      malignancies in children. It is characterized by gain of chromosomes, typically
      +X, +4, +6, +10, +14, +17, +18, and +21,+21; little is known about additional
      genetic aberrations. Approximately 20% of the patients relapse; therefore it is
      clinically important to identify risk-stratifying markers. We used SNP array
      analysis to investigate a consecutive series of 74 cases of high hyperdiploid
      ALL. We show that the characteristic chromosomal gains are even more frequent
      than previously believed, indicating that karyotyping mistakes are common, and
      that almost 80% of the cases display additional abnormalities detectable by SNP
      array analysis. Subclonality analysis strongly implied that the numerical
      aberrations were primary and arose before structural events, suggesting that step
      wise evolution of the leukemic clone is common. An association between
      duplication of 1q and +5 was seen (P = 0.003). Other frequent abnormalities
      included whole-chromosome uniparental isodisomies (wUPIDs) 9 and 11, gain of 17q
      not associated with isochromosome formation, extra gain of part of 21q, deletions
      of ETS variant 6 (ETV6), cyclin-dependent kinase inhibitor 2A (CKDN2A) and paired
      box 5 (PAX5), and PAN3 poly(A) specific ribonuclease subunit homolog (PAN3)
      microdeletions. Comparison of whole-chromosome and partial UPID9 suggested
      different pathogenetic outcomes, with the former not involving CDKN2A. Finally,
      two cases had partial deletions of AT rich interactive domain 5B (ARID5B),
      indicating that acquired as well as constitutional variants in this locus may be
      associated with pediatric ALL. Here we provide a comprehensive characterization
      of the genetic landscape of high hyperdiploid childhood ALL, including the
      heterogeneous pattern of secondary genetic events.

PMID- 21098272
TI  - Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing
      Suppressor of Fused expression.
AB  - Oligodendrocyte precursor cells (OPCs) are lineage-restricted progenitors
      generally limited in vivo to producing oligodendrocytes. Mechanisms controlling
      genesis of OPCs are of interest because of their importance in myelin development
      and their potential for regenerative therapies in multiple sclerosis and
      dysmyelinating syndromes. We show here that the SoxE transcription factors
      (comprising Sox8, 9, and 10) induce multipotent neural precursor cells (NPCs)
      from the early postnatal subventricular zone (SVZ) to become OPCs in an
      autonomous manner. We performed a chromatin immunoprecipitation-based
      bioinformatic screen and identified Suppressor of Fused (Sufu) as a direct target
      of repression by Sox10. In vitro, overexpression of Sufu blocked OPC production,
      whereas RNAi-mediated inhibition augmented OPC production. Furthermore, mice
      heterozygous for Sufu have increased numbers of OPCs in the telencephalon during
      development. We conclude that Sox10 acts to restrict the potential of NPCs toward
      the oligodendrocyte lineage in part by regulating the expression of Sufu.

PMID- 21098273
TI  - Beta-catenin activity in the dermal papilla of the hair follicle regulates
      pigment-type switching.
AB  - The switch between black and yellow pigment is mediated by the interaction
      between Melanocortin receptor 1 (Mc1r) and its antagonist Agouti, but the genetic
      and developmental mechanisms that modify this interaction to obtain different
      coat color in distinct environments are poorly understood. Here, the role of
      Wnt/beta-catenin signaling in the regulation of pigment-type switching was
      studied. Loss and gain of function of beta-catenin in the dermal papilla (DP) of
      the hair follicle results in yellow and black animals, respectively. beta-Catenin
      activity in the DP suppresses Agouti expression and activates Corin, a negative
      regulator of Agouti activity. In addition, beta-catenin activity in the DP
      regulates melanocyte activity by a mechanism that is independent of both Agouti
      and Corin. The coordinate and inverse regulation of Agouti and Corin renders
      pelage pigmentation sensitive to changes in beta-catenin activity in the DP that
      do not alter pelage structure. As a result, the signals that specify two
      biologically distinct quantitative traits are partially uncoupled despite their
      common regulation by the beta-catenin pathway in the same cells.

PMID- 21098274
TI  - Malignant cells facilitate lung metastasis by bringing their own soil.
AB  - Metastatic cancer cells (seeds) preferentially grow in the secondary sites with a
      permissive microenvironment (soil). We show that the metastatic cells can bring
      their own soil--stromal components including activated fibroblasts--from the
      primary site to the lungs. By analyzing the efferent blood from tumors, we found
      that viability of circulating metastatic cancer cells is higher if they are
      incorporated in heterotypic tumor-stroma cell fragments. Moreover, we show that
      these cotraveling stromal cells provide an early growth advantage to the
      accompanying metastatic cancer cells in the lungs. Consistent with this
      hypothesis, we demonstrate that partial depletion of the carcinoma-associated
      fibroblasts, which spontaneously spread to the lung tissue along with metastatic
      cancer cells, significantly decreases the number of metastases and extends
      survival after primary tumor resection. Finally, we show that the brain
      metastases from lung carcinoma and other carcinomas in patients contain carcinoma
      associated fibroblasts, in contrast to primary brain tumors or normal brain
      tissue. Demonstration of the direct involvement of primary tumor stroma in
      metastasis has important conceptual and clinical implications for the
      colonization step in tumor progression.

PMID- 21098275
TI  - Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis.
AB  - Aging is associated with the functional decline of cells, tissues, and organs. At
      the same time, age is the single most important prognostic factor in the
      development of most human cancers, including chronic myelogenous and acute
      lymphoblastic leukemias initiated by Bcr-Abl oncogenic translocations. Prevailing
      paradigms attribute the association between aging and cancers to the accumulation
      of oncogenic mutations over time, because the accrual of oncogenic events is
      thought to be the rate-limiting step in initiation and progression of cancers.
      Conversely, aging-associated functional decline caused by both cell-autonomous
      and non-cell-autonomous mechanisms is likely to reduce the fitness of stem and
      progenitor cell populations. This reduction in fitness should be conducive for
      increased selection of oncogenic mutations that can at least partially alleviate
      fitness defects, thereby promoting the initiation of cancers. We tested this
      hypothesis using mouse hematopoietic models. Our studies indicate that the
      dramatic decline in the fitness of aged B-lymphopoiesis coincides with altered
      receptor-associated kinase signaling. We further show that Bcr-Abl provides a
      much greater competitive advantage to old B-lymphoid progenitors compared with
      young progenitors, coinciding with restored kinase signaling pathways, and that
      this enhanced competitive advantage translates into increased promotion of Bcr
      Abl-driven leukemias. Moreover, impairing IL-7-mediated signaling is sufficient
      to promote selection for Bcr-Abl-expressing B progenitors. These studies support
      an unappreciated causative link between aging and cancer: increased selection of
      oncogenic mutations as a result of age-dependent alterations of the fitness
      landscape.

PMID- 21098276
TI  - Mature natural killer cells with phenotypic and functional alterations accumulate
      upon sustained stimulation with IL-15/IL-15Ralpha complexes.
AB  - Cytotoxic lymphocytes such as natural killer (NK) and CD8 T cells play important
      roles in immunosurveillance by killing virally infected or malignant cells. The
      homeostatic cytokine, IL-15, promotes the development, function, and survival of
      NK and CD8 T cells. IL-15 is normally presented in trans as a surface complex
      with IL-15 receptor-alpha-chain (IL-15Ralpha) by dendritic cells (DCs) and
      monocytes. Signaling by IL-15 occurs via the IL-2/IL-15 receptor beta-chain
      (CD122) which is expressed primarily by NK1.1(+) cells and CD8 T cells. The use
      of preformed complexes of IL-15 with soluble IL-15Ralpha complexes to boost the
      effector function of CD122(+) cytolytic lymphocytes such as NK and CD8 T cells
      has recently gained considerable attention. Here we describe the impact of
      transient and prolonged in vivo stimulation by IL-15/IL-15Ralpha complexes on NK
      and CD8 T cells. Whereas transitory stimulation increased the number of activated
      NK cells and significantly enhanced their effector function, prolonged
      stimulation by IL-15/IL-15Ralpha complexes led to a marked accumulation of mature
      NK cells with considerably impaired activation, cytotoxicity, and proliferative
      activity, and an altered balance of activating and inhibitory receptors. In
      contrast to NK cells, CD8 T cells exhibited an activated phenotype and robust T
      cell receptor stimulation and effector function upon chronic stimulation with IL
      15/IL-15Ralpha complexes. Thus, prolonged stimulation with the strong activating
      signal leads to a preferential accrual of mature NK cells with altered activation
      and diminished functional capacity. These findings point to a negative feedback
      mechanism to preferentially counterbalance excessive NK cell activity and may
      have important implications for cytokine immunotherapy.

PMID- 21098277
TI  - Encephalization is not a universal macroevolutionary phenomenon in mammals but is
      associated with sociality.
AB  - Evolutionary encephalization, or increasing brain size relative to body size, is
      assumed to be a general phenomenon in mammals. However, despite extensive
      evidence for variation in both absolute and relative brain size in extant
      species, there have been no explicit tests of patterns of brain size change over
      evolutionary time. Instead, allometric relationships between brain size and body
      size have been used as a proxy for evolutionary change, despite the validity of
      this approach being widely questioned. Here we relate brain size to appearance
      time for 511 fossil and extant mammalian species to test for temporal changes in
      relative brain size over time. We show that there is wide variation across groups
      in encephalization slopes across groups and that encephalization is not universal
      in mammals. We also find that temporal changes in brain size are not associated
      with allometric relationships between brain and body size. Furthermore,
      encephalization trends are associated with sociality in extant species. These
      findings test a major underlying assumption about the pattern and process of
      mammalian brain evolution and highlight the role sociality may play in driving
      the evolution of large brains.

PMID- 21098278
TI  - Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem
      and progenitor cells with proliferation potential.
AB  - Retrovirus-mediated transduction of Hoxb4 enhances hematopoietic stem cell (HSC)
      activity and enforced expression of Hoxb4 induces in vitro development of HSCs
      from differentiating mouse embryonic stem cells, but the underlying molecular
      mechanism remains unclear. We previously showed that the HSC activity was
      abrogated by accumulated Geminin, an inhibitor for the DNA replication licensing
      factor Cdt1 in mice deficient in Rae28 (also known as Phc1), which encodes a
      member of Polycomb-group complex 1. In this study we found that Hoxb4
      transduction reduced accumulated Geminin in Rae28-deficient mice, despite
      increasing the mRNA, and restored the impaired HSC activity. Supertransduction of
      Geminin suppressed the HSC activity induced by Hoxb4 transduction, whereas
      knockdown of Geminin promoted the clonogenic and replating activities, indicating
      the importance of Geminin regulation in the molecular mechanism underlying Hoxb4
      transduction-mediated enhancement of the HSC activity. This facilitated our
      investigation of how transduced Hoxb4 reduced Geminin. We showed in vitro and in
      vivo that Hoxb4 and the Roc1 (also known as Rbx1)-Ddb1-Cul4a ubiquitin ligase
      core component formed a complex designated as RDCOXB4, which acted as an E3
      ubiquitin ligase for Geminin and down-regulated Geminin through the ubiquitin
      proteasome system. Down-regulated Geminin and the resultant E2F activation may
      provide cells with proliferation potential by increasing a DNA prereplicative
      complex loaded onto chromatin. Here we suggest that transduced Hoxb4 down
      regulates Geminin protein probably by constituting the E3 ubiquitin ligase for
      Geminin to provide hematopoietic stem and progenitor cells with proliferation
      potential.

PMID- 21098279
TI  - Recognition of tandem PxxP motifs as a unique Src homology 3-binding mode
      triggers pathogen-driven actin assembly.
AB  - Src homology 3 (SH3) domains are globular protein interaction modules that
      regulate cell behavior. The classic SH3 ligand-binding site accommodates a
      hydrophobic PxxP motif and a positively charged specificity-determining residue.
      We have determined the NMR structure of insulin receptor tyrosine kinase
      substrate (IRTKS) SH3 domain in complex with a repeat from Escherichia coli
      secreted protein F-like protein encoded on prophage U (EspF(U)), a translocated
      effector of enterohemorrhagic E. coli that commandeers the mammalian actin
      assembly machinery. EspF(U)-IRTKS interaction is among the highest affinity
      natural SH3 ligands. Our complex structure reveals a unique type of SH3
      interaction based on recognition of tandem PxxP motifs in the ligand. Strikingly,
      the specificity pocket of IRTKS SH3 has evolved to accommodate a polyproline type
      II helical peptide analogously to docking of the canonical PxxP by the conserved
      IRTKS SH3 proline-binding pockets. This cooperative binding explains the high
      affinity SH3 interaction and is required for EspF(U)-IRTKS interaction in
      mammalian cells as well as the formation of localized actin "pedestals" beneath
      bound bacteria. Importantly, tandem PxxP motifs are also found in mammalian
      ligands and have been shown to contribute to IRTKS SH3 recognition similarly.

PMID- 21098280
TI  - Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.
AB  - Nucleotide variations, including SNPs, in the coding regions of disease genes are
      important targets for RNAi treatment, which is a promising medical treatment for
      intractable diseases such as triplet repeat diseases. However, the identification
      of such nucleotide variations and the design of siRNAs conferring disease allele
      specific RNAi are quite difficult. In this study we developed a pull-down method
      to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease
      causing alleles, and we demonstrated disease allele-specific RNAi that targeted
      cSNP sites in mutant Huntingtin alleles, each of which possessed a different cSNP
      haplotype. Therefore, the methods presented here allow for allele-specific RNAi
      knockdown against disease-causing alleles by using siRNAs specific to disease
      linked cSNP haplotypes, and advanced progress toward tailor-made RNAi treatments
      for triplet repeat diseases.

PMID- 21098281
TI  - Using return on investment to maximize conservation effectiveness in Argentine
      grasslands.
AB  - The rapid global loss of natural habitats and biodiversity, and limited
      resources, place a premium on maximizing the expected benefits of conservation
      actions. The scarcity of information on the fine-grained distribution of species
      of conservation concern, on risks of loss, and on costs of conservation actions,
      especially in developing countries, makes efficient conservation difficult. The
      distribution of ecosystem types (unique ecological communities) is typically
      better known than species and arguably better represents the entirety of
      biodiversity than do well-known taxa, so we use conserving the diversity of
      ecosystem types as our conservation goal. We define conservation benefit to
      include risk of conversion, spatial effects that reward clumping of habitat, and
      diminishing returns to investment in any one ecosystem type. Using Argentine
      grasslands as an example, we compare three strategies: protecting the cheapest
      land ("minimize cost"), maximizing conservation benefit regardless of cost
      ("maximize benefit"), and maximizing conservation benefit per dollar ("return on
      investment"). We first show that the widely endorsed goal of saving some
      percentage (typically 10%) of a country or habitat type, although it may inspire
      conservation, is a poor operational goal. It either leads to the accumulation of
      areas with low conservation benefit or requires infeasibly large sums of money,
      and it distracts from the real problem: maximizing conservation benefit given
      limited resources. Second, given realistic budgets, return on investment is
      superior to the other conservation strategies. Surprisingly, however, over a wide
      range of budgets, minimizing cost provides more conservation benefit than does
      the maximize-benefit strategy.

PMID- 21098282
TI  - Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces
      its oligomerization.
AB  - Increasing evidence supports a vascular contribution to Alzheimer's disease (AD),
      but a direct connection between AD and the circulatory system has not been
      established. Previous work has shown that blood clots formed in the presence of
      the beta-amyloid peptide (Abeta), which has been implicated in AD, have an
      abnormal structure and are resistant to degradation in vitro and in vivo. In the
      present study, we show that Abeta specifically interacts with fibrinogen with a
      K(d) of 26.3 +/- 6.7 nM, that the binding site is located near the C terminus of
      the fibrinogen beta-chain, and that the binding causes fibrinogen to oligomerize.
      These results suggest that the interaction between Abeta and fibrinogen modifies
      fibrinogen's structure, which may then lead to abnormal fibrin clot formation.
      Overall, our study indicates that the interaction between Abeta and fibrinogen
      may be an important contributor to the vascular abnormalities found in AD.

PMID- 21098283
TI  - Identifying barriers to Muslim integration in France.
AB  - Is there a Muslim disadvantage in economic integration for second-generation
      immigrants to Europe? Previous research has failed to isolate the effect that
      religion may have on an immigrant family's labor market opportunities because
      other factors, such as country of origin or race, confound the result. This paper
      uses a correspondence test in the French labor market to identify and measure
      this religious effect. The results confirm that in the French labor market, anti
      Muslim discrimination exists: a Muslim candidate is 2.5 times less likely to
      receive a job interview callback than is his or her Christian counterpart. A high
      n survey reveals, consistent with expectations from the correspondence test, that
      second-generation Muslim households in France have lower income compared with
      matched Christian households. The paper thereby contributes to both substantive
      debates on the Muslim experience in Europe and methodological debates on how to
      measure discrimination. Following the National Academy of Sciences' 2001
      recommendations on combining a variety of methodologies and applying them to real
      world situations, this research identifies, measures, and infers consequences of
      discrimination based on religious affiliation, controlling for potentially
      confounding factors, such as race and country of origin.

PMID- 21098284
TI  - DNA damage regulates the mobility of Brca2 within the nucleoplasm of living
      cells.
AB  - How the biochemical reactions that lead to the repair of DNA damage are
      controlled by the diffusion and availability of protein reactants within the
      nucleoplasm is poorly understood. Here, we use gene targeting to replace Brca2 (a
      cancer suppressor protein essential for DNA repair) with a functional enhanced
      green fluorescent protein (EGFP)-tagged form, followed by fluorescence
      correlation spectroscopy to measure Brca2-EGFP diffusion in the nucleoplasm of
      living cells exposed to DNA breakage. Before damage, nucleoplasmic Brca2
      molecules exhibit complex states of mobility, with long dwell times within a sub
      fL observation volume, indicative of restricted motion. DNA damage significantly
      enhances the mobility of Brca2 molecules in the S/G2 phases of the cell cycle,
      via signaling through damage-activated protein kinases. Brca2 mobilization is
      accompanied by increased binding within the nucleoplasm to its cargo, the Rad51
      recombinase, measured by fluorescence cross-correlation spectroscopy. Together,
      these results suggest that DNA breakage triggers the redistribution of soluble
      nucleoplasmic Brca2 molecules from a state of restricted diffusion, into a mobile
      fraction available for Rad51 binding. Our findings identify signal-regulated
      changes in nucleoplasmic protein diffusion as a means to control biochemical
      reactions in the cell nucleus.

PMID- 21098285
TI  - Biodiversity can support a greener revolution in Africa.
AB  - The Asian green revolution trebled grain yields through agrochemical
      intensification of monocultures. Associated environmental costs have subsequently
      emerged. A rapidly changing world necessitates sustainability principles be
      developed to reinvent these technologies and test them at scale. The need is
      particularly urgent in Africa, where ecosystems are degrading and crop yields
      have stagnated. An unprecedented opportunity to reverse this trend is unfolding
      in Malawi, where a 90% subsidy has ensured access to fertilization and improved
      maize seed, with substantive gains in productivity for millions of farmers. To
      test if economic and ecological sustainability could be improved, we preformed
      manipulative experimentation with crop diversity in a countrywide trial (n = 991)
      and at adaptive, local scales through a decade of participatory research (n =
      146). Spatial and temporal treatments compared monoculture maize with legume
      diversified maize that included annual and semiperennial (SP) growth habits in
      temporal and spatial combinations, including rotation, SP rotation, intercrop,
      and SP intercrop systems. Modest fertilizer intensification doubled grain yield
      compared with monoculture maize. Biodiversity improved ecosystem function
      further: SP rotation systems at half-fertilizer rates produced equivalent
      quantities of grain, on a more stable basis (yield variability reduced from 22%
      to 13%) compared with monoculture. Across sites, profitability and farmer
      preference matched: SP rotations provided twofold superior returns, whereas
      diversification of maize with annual legumes provided more modest returns. In
      this study, we provide evidence that in Africa, crop diversification can be
      effective at a countrywide scale, and that shrubby, grain legumes can enhance
      environmental and food security.

PMID- 21098286
TI  - Trial-to-trial variability of the prefrontal neurons reveals the nature of their
      engagement in a motion discrimination task.
AB  - During motion discrimination tasks, many prefrontal cortex (PFC) neurons are
      strongly modulated by the behavioral context, suggesting their involvement in
      sensory discriminations. Recent studies suggest that trial-to-trial variability
      of spiking activity characteristic of cortical neurons could be a source of
      information about the state of neurons and their participation in behavioral
      tasks. We tested this hypothesis by examining the variability of putative
      pyramidal PFC neurons, a likely source of top-down influences. The variability of
      these neurons was calculated as a ratio of spike count variance to its mean (fano
      factor, FF), while monkeys compared the directions of two moving stimuli, sample
      and test, separated by a delay. We found that the FF tracked consecutive
      components of the task, dropping rapidly with the onset of stimuli being
      discriminated and declining more slowly before each salient event of the trial:
      The sample, the test, and the response. These time-dependent signals were less
      consistent in direction selective neurons and were largely absent during passive
      fixation. Furthermore, neurons with test responses that reflected the remembered
      sample decreased their FF well before the test, revealing the predictive nature
      of response variability, an effect present only during the active task. The FF
      was also sensitive to behavioral performance, exhibiting different temporal
      dynamics on error trials. These changes did not depend on firing rates and were
      often the only metric correlated with task demands. Our results demonstrate that
      trial-to-trial variability provides a sensitive measure of the engagement of
      putative pyramidal PFC neurons in circuits subserving discrimination tasks.

PMID- 21098287
TI  - Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A
      (PP2A) signaling.
AB  - Hyperphosphorylated tau plays an important role in the formation of
      neurofibrillary tangles in brains of patients with Alzheimer's disease (AD) and
      related tauopathies and is a crucial factor in the pathogenesis of these
      disorders. Though diverse kinases have been implicated in tau phosphorylation,
      protein phosphatase 2A (PP2A) seems to be the major tau phosphatase. Using murine
      primary neurons from wild-type and human tau transgenic mice, we show that the
      antidiabetic drug metformin induces PP2A activity and reduces tau phosphorylation
      at PP2A-dependent epitopes in vitro and in vivo. This tau dephosphorylating
      potency can be blocked entirely by the PP2A inhibitors okadaic acid and
      fostriecin, confirming that PP2A is an important mediator of the observed
      effects. Surprisingly, metformin effects on PP2A activity and tau phosphorylation
      seem to be independent of AMPK activation, because in our experiments (i)
      metformin induces PP2A activity before and at lower levels than AMPK activity and
      (ii) the AMPK activator AICAR does not influence the phosphorylation of tau at
      the sites analyzed. Affinity chromatography and immunoprecipitation experiments
      together with PP2A activity assays indicate that metformin interferes with the
      association of the catalytic subunit of PP2A (PP2Ac) to the so-called MID1-alpha4
      protein complex, which regulates the degradation of PP2Ac and thereby influences
      PP2A activity. In summary, our data suggest a potential beneficial role of
      biguanides such as metformin in the prophylaxis and/or therapy of AD.

PMID- 21098288
TI  - Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative
      enzyme loss due to abnormal interaction with TCP1 and c-Cbl.
AB  - Gaucher disease (GD), the most common lysosomal storage disorder of humans, is
      caused by mutations in the gene coding for the enzyme glucocerebrosidase (GCase).
      Clinical manifestations vary among patients with the three types of GD, and
      phenotypic heterogeneity occurs even among patients with identical mutations. To
      gain insight into why phenotypic heterogeneity occurs in GD, we investigated
      mechanisms underlying the net loss of GCase catalytic activity in cultured skin
      fibroblasts derived from patients with the three types of GD. The findings
      indicate that the loss of catalytic activity of GCase correlates with its
      quantitative reduction, rather than a decrease in functional capacity of mutant
      enzyme. Use of a proteasome inhibitor, lactacystin, resulted in increased
      expression of GCase, suggesting a mechanism of protein degradation in GD.
      Furthermore, reduced binding of GCase to TCP1 ring complex (TRiC), a regulator of
      correct protein folding, may result in defective maturation of nascent GCase in
      GD cells. Additionally, increased interaction between GCase and c-Cbl, an E3
      ubiquitin ligase, may be involved in the degradation and loss of GCase in GD. The
      findings suggest that specific molecular mediators involved in GCase maturation
      and degradation could be responsible for phenotypic variation among patients with
      the same genotypes and that these mediators could be therapeutically targeted to
      increase GCase activity in patients with GD.

PMID- 21098289
TI  - A vesicle carrier that mediates peroxisome protein traffic from the endoplasmic
      reticulum.
AB  - Pex19p, a soluble cytoplasmic transport protein, is required for the traffic of
      the peroxisomal membrane proteins Pex3p and Pex15p from the endoplasmic reticulum
      (ER) to the peroxisome. We documented Pex15p traffic from the ER using a chimeric
      protein containing a C-terminal glycosylation acceptor peptide. Pex15Gp expressed
      in wild-type yeast cells is N-glycosylated and functions properly in the
      peroxisome. In contrast, pex19Delta-mutant cells accumulate the glycoprotein
      Pex15Gp in the ER. We developed a cell-free preperoxisomal vesicle-budding
      reaction in which Pex15Gp and Pex3p are packaged into small vesicles in the
      presence of cytosol, Pex19p, and ATP. Secretory vesicle budding (COPII) detected
      by the packaging of a SNARE protein (soluble N-ethylmaleimide-sensitive
      attachment protein receptor) occurs in the same incubation but does not depend on
      Pex19p. Conversely a dominant GTPase mutant Sar1p which inhibits COPII has no
      effect on Pex3p packaging. Pex15Gp and Pex3p budded vesicles sediment as low
      buoyant-density membranes on a Nycodenz gradient and copurify by affinity
      isolation using native but not Triton X-100-treated budded vesicles. ER
      peroxisome transport vesicles appear to rely on a novel budding mechanism
      requiring Pex19p and additional unknown factors.

PMID- 21098290
TI  - Pituitary growth hormone network responses are sexually dimorphic and regulated
      by gonadal steroids in adulthood.
AB  - There are well-recognized sex differences in many pituitary endocrine axes,
      usually thought to be generated by gonadal steroid imprinting of the
      neuroendocrine hypothalamus. However, the recognition that growth hormone (GH)
      cells are arranged in functionally organized networks raises the possibility that
      the responses of the network are different in males and females. We studied this
      by directly monitoring the calcium responses to an identical GH-releasing hormone
      (GHRH) stimulus in populations of individual GH cells in slices taken from male
      and female murine GH-eGFP pituitary glands. We found that the GH cell network
      responses are sexually dimorphic, with a higher proportion of responding cells in
      males than in females, correlated with greater GH release from male slices.
      Repetitive waves of calcium spiking activity were triggered by GHRH in some
      males, but were never observed in females. This was not due to a permanent
      difference in the network architecture between male and female mice; rather, the
      sex difference in the proportions of GH cells responding to GHRH were switched by
      postpubertal gonadectomy and reversed with hormone replacements, suggesting that
      the network responses are dynamically regulated in adulthood by gonadal steroids.
      Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH
      secretion that play an important role in differences in growth and metabolism
      between the sexes.

PMID- 21098291
TI  - Altered antisense-to-sense transcript ratios in breast cancer.
AB  - Transcriptome profiling studies suggest that a large fraction of the genome is
      transcribed and many transcripts function independent of their protein coding
      potential. The relevance of noncoding RNAs (ncRNAs) in normal physiological
      processes and in tumorigenesis is increasingly recognized. Here, we describe
      consistent and significant differences in the distribution of sense and antisense
      transcripts between normal and neoplastic breast tissues. Many of the
      differentially expressed antisense transcripts likely represent long ncRNAs. A
      subset of genes that mainly generate antisense transcripts in normal but not
      cancer cells is involved in essential metabolic processes. These findings suggest
      fundamental differences in global RNA regulation between normal and cancer cells
      that might play a role in tumorigenesis.

PMID- 21098292
TI  - Viral replicative capacity is the primary determinant of lymphocytic
      choriomeningitis virus persistence and immunosuppression.
AB  - The Clone 13 (Cl13) strain of lymphocytic choriomeningitis virus is widely
      studied as a model of chronic systemic viral infection. Here, we used reverse
      genetic techniques to identify the molecular basis of Cl13 persistence and
      immunosuppression, the characteristics differentiating it from the closely
      related Armstrong strain. We found that a single-point mutation in the Cl13
      polymerase was necessary and partially sufficient for viral persistence and
      immunosuppression. A glycoprotein mutation known to enhance dendritic cell
      targeting accentuated both characteristics but when introduced alone, failed to
      alter the phenotype of the Armstrong strain. The decisive polymerase mutation
      increased intracellular viral RNA load in plasmacytoid dendritic cells, which we
      identified as a main initial target cell type in vivo, and increased viremia in
      the early phase of infection. These findings establish the enhanced replicative
      capacity as the primary determinant of the Cl13 phenotype. Viral persistence and
      immunosuppression can, thus, represent a direct consequence of excessive viral
      replication overwhelming the host's antiviral defense.

PMID- 21098293
TI  - Rapid efficient coding of correlated complex acoustic properties.
AB  - Natural sounds are complex, typically changing along multiple acoustic dimensions
      that covary in accord with physical laws governing sound-producing sources. We
      report that, after passive exposure to novel complex sounds, highly correlated
      features initially collapse onto a single perceptual dimension, capturing
      covariance at the expense of unitary stimulus dimensions. Discriminability of
      sounds respecting the correlation is maintained, but is temporarily lost for
      sounds orthogonal or oblique to experienced covariation. Following extended
      experience, perception of variance not captured by the correlation is restored,
      but weighted only in proportion to total experienced covariance. A Hebbian neural
      network model captures some aspects of listener performance; an anti-Hebbian
      model captures none; but, a principal components analysis model captures the full
      pattern of results. Predictions from the principal components analysis model also
      match evolving listener performance in two discrimination tasks absent passive
      listening. These demonstrations of adaptation to correlated attributes provide
      direct behavioral evidence for efficient coding.

PMID- 21098294
TI  - Dicer controls CD8+ T-cell activation, migration, and survival.
AB  - The RNaseIII enzyme Dicer is required for mature microRNA production. Although
      extensive investigation has been carried out to determine the role of
      Dicer/miRNAs in the immune system, their function in mature CD8(+) T cells has
      not been examined. We deleted Dicer in mature polyclonal and TCR transgenic
      CD8(+) T cells using either tat-cre or the distal lck promoter, which drives cre
      expression after the stage of positive selection. Following antigenic challenge
      by a pathogen infection in vivo, Dicer-deleted CD8(+) T cells failed to
      accumulate at the usual peak of the response. Surprisingly however, we found that
      deletion of Dicer in mature CD8(+) T cells allowed them to respond more rapidly
      than control cells to TCR stimuli in vitro. In response to anti-CD3 plus anti
      CD28 stimulation, Dicer-deleted T cells up-regulated CD69 faster and entered the
      first mitosis earlier than control T cells. In addition, activated Dicer(-/-)
      cells failed to rapidly down-regulate CD69 when removed from the TCR stimulus. As
      a probable consequence of this sustained CD69 expression, Dicer(-/-) T cells
      showed defective migration out of the central lymphoid organs in vivo. We
      identify miR-130/301, which are dramatically up-regulated following T-cell
      activation, as able to down-regulate CD69 expression via binding to a conserved
      site in the 3'UTR of CD69 mRNA. Thus, cellular functions dependent on Dicer
      expression are not required for the early steps in CD8(+) T-cell activation, but
      are essential for their survival and accumulation.

PMID- 21098295
TI  - Structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer
      resolution.
AB  - The structure of the 26S proteasome from Schizosaccharomyces pombe has been
      determined to a resolution of 9.1 A by cryoelectron microscopy and single
      particle analysis. In addition, chemical cross-linking in conjunction with mass
      spectrometry has been used to identify numerous residue pairs in close proximity
      to each other, providing an array of spatial restraints. Taken together these
      data clarify the topology of the AAA-ATPase module in the 19S regulatory particle
      and its spatial relationship to the alpha-ring of the 20S core particle. Image
      classification and variance analysis reveal a belt of high "activity" surrounding
      the AAA-ATPase module which is tentatively assigned to the reversible association
      of proteasome interacting proteins and the conformational heterogeneity among the
      particles. An integrated model is presented which sheds light on the early steps
      of protein degradation by the 26S complex.

PMID- 21098296
TI  - Cation-pi interaction regulates ligand-binding affinity and signaling of integrin
      alpha4beta7.
AB  - Integrin alpha(4)beta(7) mediates rolling and firm adhesion of leucocytes, two of
      the critical steps in leukocyte migration and tissue specific homing. Affinity of
      alpha(4)beta(7) for ligand is dynamically regulated by three interlinked metal
      ion-binding sites in beta(7)-subunit I domain. In this study, we found that
      Phe185 (F185), a highly conserved aromatic residue in beta(7)-subunit, links the
      specificity-determining loop and the synergistic metal ion-binding site (SyMBS)
      through cation-pi interaction. Mutations of F185 that disrupted the SyMBS cation
      F185 interaction led to deficient firm cell adhesion mediated by high affinity
      alpha(4)beta(7), and only slightly affected rolling adhesion mediated by low
      affinity alpha(4)beta(7). Disruption of SyMBS cation-F185 interaction induced
      partial extension of integrin ectodomain and separation of cytoplasmic tails, and
      impaired alpha(4)beta(7)-mediated bidirectional signaling. In addition, loss of
      SyMBS cation-F185 interaction increased paxillin expression and promoted paxillin
      integrin binding, leading to deficient cell spreading. Furthermore, integrin
      alpha(4)beta(7)-mediated cell migration was decreased by the abolishment of SyMBS
      cation-F185 interaction. Thus, these findings reveal a cation-pi interaction
      playing vital roles in the regulation of integrin affinity, signaling, and
      biological functions.

PMID- 21098297
TI  - Directed epitope delivery across the Escherichia coli outer membrane through the
      porin OmpF.
AB  - The porins OmpF and OmpC are trimeric beta-barrel proteins with narrow channels
      running through each monomer that exclude molecules > 600 Da while mediating the
      passive diffusion of small nutrients and metabolites across the Gram-negative
      outer membrane (OM). Here, we elucidate the mechanism by which an entire soluble
      protein domain (> 6 kDa) is delivered through the lumen of such porins. Following
      high-affinity binding to the vitamin B(12) receptor in Escherichia coli, the
      bacteriocin ColE9 recruits OmpF or OmpC using an 83-residue intrinsically
      unstructured translocation domain (IUTD) to deliver a 16-residue TolB-binding
      epitope (TBE) in the center of the IUTD to the periplasm where it triggers toxin
      entry. We demonstrate that the IUTD houses two OmpF-binding sites, OBS1 (residues
      2-18) and OBS2 (residues 54-63), which flank the TBE and bind with K(d)s of 2 and
      24 MUM, respectively, at pH 6.5 and 25 oC. We show the two OBSs share the same
      binding site on OmpF and that the colicin must house at least one of them for
      antibiotic activity. Finally, we report the structure of the OmpF-OBS1 complex
      that shows the colicin bound within the porin lumen spanning the membrane
      bilayer. Our study explains how colicins exploit porins to deliver epitope
      signals to the bacterial periplasm and, more broadly, how the inherent
      flexibility and narrow cross-sectional area of an IUP domain can endow it with
      the ability to traverse a biological membrane via the constricted lumen of a beta
      barrel membrane protein.

PMID- 21098298
TI  - Dry amyloid fibril assembly in a yeast prion peptide is mediated by long-lived
      structures containing water wires.
AB  - Amyloid-like fibrils from a number of small peptides that are unrelated by
      sequence adopt a cross-beta-spine in which the two sheets fully interdigitate to
      create a dry interface. Formation of such a dry interface is usually associated
      with self-assembly of extended hydrophobic surfaces. Here we investigate how a
      dry interface is created in the process of protofilament formation in vastly
      different sequences using two amyloidogenic peptides, one a polar sequence from
      the N terminus of the yeast prion Sup35 and the other a predominantly hydrophobic
      sequence from the C terminus of Abeta-peptide. Using molecular dynamics
      simulations with three force fields we show that spontaneous formation of two
      ordered one-dimensional water wires in the pore between the two sheets of the
      Sup35 protofilaments results in long-lived structures, which are stabilized by a
      network of hydrogen bonds between the water molecules in the wires and the polar
      side chains in the beta-sheet. Upon decreasing the stability of the metastable
      structures, water molecules are expelled resulting in a helically twisted
      protofilament in which side chains from a pair of beta-strands in each sheet pack
      perfectly resulting in a dry interface. Although drying in hydrophobically
      dominated interfaces is abrupt, resembling a liquid to vapor transition, we find
      that discrete transitions between the liquid to one-dimensional ordered water in
      the nanopore enclosed by the two beta-sheets to dry interface formation
      characterizes protofilament assembly in the yeast prions. Indeed, as the two
      sheets of the hydrophobic Abeta-sequence approach each other, fibril formation
      and expulsion of water molecules occur rapidly and nearly simultaneously.

PMID- 21098300
TI  - Time-dependent electron phenomena at surfaces.
AB  - Femtosecond and subfemtosecond time scales typically rule electron dynamics at
      metal surfaces. Recent advance in experimental techniques permits now remarkable
      precision in the description of these processes. In particular, shorter time
      scales, smaller system sizes, and spin-dependent effects are current targets of
      interest. In this article, we use state-of-the-art theoretical methods to analyze
      these refined features of electron dynamics. We show that the screening of
      localized charges at metal surfaces is created locally in the attosecond time
      scale, while collective excitations transfer the perturbation to larger distances
      in longer time scales. We predict that the elastic width of the resonance in
      excited alkali adsorbates on ferromagnetic surfaces can depend on spin
      orientation in a counterintuitive way. Finally, we quantitatively evaluate the
      electron-electron and electron-phonon contributions to the electronic excited
      states widths in ultrathin metal layers. We conclude that confinement and spin
      effects are key factors in the behavior of electron dynamics at metal surfaces.

PMID- 21098299
TI  - Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized
      in the most common form of familial amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a disorder characterized by the death of
      both upper and lower motor neurons and by 3- to 5-yr median survival
      postdiagnosis. The only US Food and Drug Administration-approved drug for the
      treatment of ALS, Riluzole, has at best, moderate effect on patient survival and
      quality of life; therefore innovative approaches are needed to combat
      neurodegenerative disease. Some familial forms of ALS (fALS) have been linked to
      mutations in the Cu/Zn superoxide dismutase (SOD1). The dominant inheritance of
      mutant SOD1 and lack of symptoms in knockout mice suggest a "gain of toxic
      function" as opposed to a loss of function. A prevailing hypothesis for the
      mechanism of the toxicity of fALS-SOD1 variants, or the gain of toxic function,
      involves dimer destabilization and dissociation as an early step in SOD1
      aggregation. Therefore, stabilizing the SOD1 dimer, thus preventing aggregation,
      is a potential therapeutic strategy. Here, we report a strategy in which we
      chemically cross-link the SOD1 dimer using two adjacent cysteine residues on each
      respective monomer (Cys111). Stabilization, measured as an increase in melting
      temperature, of ~20  degrees C and ~45  degrees C was observed for two mutants,
      G93A and G85R, respectively. This stabilization is the largest for SOD1, and to
      the best of our knowledge, for any disease-related protein. In addition, chemical
      cross-linking conferred activity upon G85R, an otherwise inactive mutant. These
      results demonstrate that targeting these cysteine residues is an important new
      strategy for development of ALS therapies.

PMID- 21098301
TI  - Luminescent nanocrystal stress gauge.
AB  - Microscale mechanical forces can determine important outcomes ranging from the
      site of material fracture to stem cell fate. However, local stresses in a vast
      majority of systems cannot be measured due to the limitations of current
      techniques. In this work, we present the design and implementation of the CdSe
      CdS core-shell tetrapod nanocrystal, a local stress sensor with bright
      luminescence readout. We calibrate the tetrapod luminescence response to stress
      and use the luminescence signal to report the spatial distribution of local
      stresses in single polyester fibers under uniaxial strain. The bright stress
      dependent emission of the tetrapod, its nanoscale size, and its colloidal nature
      provide a unique tool that may be incorporated into a variety of micromechanical
      systems including materials and biological samples to quantify local stresses
      with high spatial resolution.

PMID- 21098303
TI  - Rotational and constitutional dynamics of caged supramolecules.
AB  - The confinement of molecular species in nanoscale environments leads to
      intriguing dynamic phenomena. Notably, the organization and rotational motions of
      individual molecules were controlled by carefully designed, fully supramolecular
      host architectures. Here we use an open 2D coordination network on a smooth metal
      surface to steer the self-assembly of discrete trimeric guest units, identified
      as noncovalently bound dynamers. Each caged chiral supramolecule performs
      concerted, chirality-preserving rotary motions within the template honeycomb
      pore, which are visualized and quantitatively analyzed using temperature
      controlled scanning tunneling microscopy. Furthermore, with higher thermal
      energies, a constitutional system dynamics appears, which is revealed by
      monitoring repetitive switching events of the confined supramolecules' chirality
      signature, reflecting decay and reassembly of the caged units.

PMID- 21098302
TI  - Helicobacter pylori proinflammatory protein up-regulates NF-kappaB as a cell
      translocating Ser/Thr kinase.
AB  - There has been considerable interest in virulence genes in the plasticity region
      of Helicobacter pylori, but little is known about many of these genes. JHP940,
      one of the virulence factors encoded by the plasticity region of H. pylori strain
      J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and
      interleukin-8 secretion as well as enhanced translocation of NF-kappaB in
      cultured macrophages. Here we have characterized the structure and function of
      JHP940 to provide the framework for better understanding its role in inflammation
      by H. pylori. Our work demonstrates that JHP940 is the first example of a
      eukaryotic-type Ser/Thr kinase from H. pylori. We show that JHP940 is
      catalytically active as a protein kinase and translocates into cultured human
      cells. Furthermore, the kinase activity is indispensable for indirectly up
      regulating phosphorylation of NF-kappaB p65 at Ser276. Our results, taken
      together, contribute significantly to understanding the molecular basis of the
      role of JHP940 in inflammation and subsequent pathogenesis caused by H. pylori.
      We propose to rename the jhp940 gene as ctkA (cell translocating kinase A).

PMID- 21098304
TI  - Free energy profiles from single-molecule pulling experiments.
AB  - Nonequilibrium pulling experiments provide detailed information about the
      thermodynamic and kinetic properties of molecules. We show that unperturbed free
      energy profiles as a function of molecular extension can be obtained rigorously
      from such experiments without using work-weighted position histograms. An inverse
      Weierstrass transform is used to relate the system free energy obtained from the
      Jarzynski equality directly to the underlying molecular free energy surface. An
      accurate approximation for the free energy surface is obtained by using the
      method of steepest descent to evaluate the inverse transform. The formalism is
      applied to simulated data obtained from a kinetic model of RNA folding, in which
      the dynamics consists of jumping between linker-dominated folded and unfolded
      free energy surfaces.

PMID- 21098305
TI  - Teleportation-based realization of an optical quantum two-qubit entangling gate.
AB  - In recent years, there has been heightened interest in quantum teleportation,
      which allows for the transfer of unknown quantum states over arbitrary distances.
      Quantum teleportation not only serves as an essential ingredient in long-distance
      quantum communication, but also provides enabling technologies for practical
      quantum computation. Of particular interest is the scheme proposed by D.
      Gottesman and I. L. Chuang [(1999) Nature 402:390-393], showing that quantum
      gates can be implemented by teleporting qubits with the help of some special
      entangled states. Therefore, the construction of a quantum computer can be simply
      based on some multiparticle entangled states, Bell-state measurements, and single
      qubit operations. The feasibility of this scheme relaxes experimental constraints
      on realizing universal quantum computation. Using two different methods, we
      demonstrate the smallest nontrivial module in such a scheme--a teleportation
      based quantum entangling gate for two different photonic qubits. One uses a high
      fidelity six-photon interferometer to realize controlled-NOT gates, and the other
      uses four-photon hyperentanglement to realize controlled-Phase gates. The results
      clearly demonstrate the working principles and the entangling capability of the
      gates. Our experiment represents an important step toward the realization of
      practical quantum computers and could lead to many further applications in linear
      optics quantum information processing.

PMID- 21098306
TI  - Protein structure determination by exhaustive search of Protein Data Bank derived
      databases.
AB  - Parallel sequence and structure alignment tools have become ubiquitous and
      invaluable at all levels in the study of biological systems. We demonstrate the
      application and utility of this same parallel search paradigm to the process of
      protein structure determination, benefitting from the large and growing corpus of
      known structures. Such searches were previously computationally intractable.
      Through the method of Wide Search Molecular Replacement, developed here, they can
      be completed in a few hours with the aide of national-scale federated
      cyberinfrastructure. By dramatically expanding the range of models considered for
      structure determination, we show that small (less than 12% structural coverage)
      and low sequence identity (less than 20% identity) template structures can be
      identified through multidimensional template scoring metrics and used for
      structure determination. Many new macromolecular complexes can benefit
      significantly from such a technique due to the lack of known homologous protein
      folds or sequences. We demonstrate the effectiveness of the method by determining
      the structure of a full-length p97 homologue from Trichoplusia ni. Example cases
      with the MHC/T-cell receptor complex and the EmoB protein provide systematic
      estimates of minimum sequence identity, structure coverage, and structural
      similarity required for this method to succeed. We describe how this structure
      search approach and other novel computationally intensive workflows are made
      tractable through integration with the US national computational
      cyberinfrastructure, allowing, for example, rapid processing of the entire
      Structural Classification of Proteins protein fragment database.

PMID- 21098307
TI  - Organization of the polarization splay modulated smectic liquid crystal phase by
      topographic confinement.
AB  - Recently, the topographic patterning of surfaces by lithography and
      nanoimprinting has emerged as a new and powerful tool for producing single
      structural domains of liquid crystals and other soft materials. Here the use of
      surface topography is extended to the organization of liquid crystals of bent
      core molecules, soft materials that, on the one hand, exhibit a rich, exciting,
      and intensely studied array of novel phases, but that, on the other hand, have
      proved very difficult to align. Among the most notorious in this regard are the
      polarization splay modulated (B7) phases, in which the symmetry-required
      preference for ferroelectric polarization to be locally bouquet-like or "splayed"
      is expressed. Filling space with splay of a single sign requires defects and in
      the B7 splay is accommodated in the form of periodic splay stripes spaced by
      defects and coupled to smectic layer undulations. Upon cooling from the isotropic
      phase this structure grows via a first order transition in the form of an exotic
      array of twisted filaments and focal conic defects that are influenced very
      little by classic alignment methods. By contrast, growth under conditions of
      confinement in rectangular topographic channels is found to produce completely
      new growth morphology, generating highly ordered periodic layering patterns. The
      resulting macroscopic order will be of great use in further exploration of the
      physical properties of bent-core phases and offers a route for application of
      difficult-to-align soft materials as are encountered in organic electronic and
      optical applications.

PMID- 21098308
TI  - Anabaena sensory rhodopsin is a light-driven unidirectional rotor.
AB  - The implementation of multiconfigurational quantum chemistry methods into a
      quantum-mechanics/molecular-mechanics protocol has allowed the construction of a
      realistic computer model for the sensory rhodopsin of the cyanobacterium Anabaena
      PCC 7120. The model, which reproduces the absorption spectra of both the all
      trans and 13-cis forms of the protein and their associated K and L intermediates,
      is employed to investigate the light-driven steps of the photochromic cycle
      exhibited by the protein. It is found that the photoisomerizations of the all
      trans and 13-cis retinal chromophores occur through unidirectional,
      counterclockwise 180 degrees  rotations of the =C14-C15= moiety with respect to
      the Lys210-linked end of the chromophore axis. Thus, the sequential
      interconversions of the all-trans and 13-cis forms during a single photochromic
      cycle yield a complete (360 degrees ) unidirectional rotation of the =C14-C15=
      moiety. This finding implies that Anabaena sensory rhodopsin is a biological
      realization of a light-driven molecular rotor.

PMID- 21098309
TI  - Metal spectra as indicators of development.
AB  - We have assembled extensive information on the cycles of seven industrial metals
      in 49 countries, territories, or groups of countries, drawn from a database of
      some 200,000 material flows, and have devised analytical approaches to treat the
      suite of metals as composing an approach to a national "materials metabolism." We
      demonstrate that in some of the more developed countries, per capita metal use is
      more than 10 times the global average. Additionally, countries that use more than
      the per capita world average of any metal do so for all metals, and vice versa,
      and countries that are above global average rates of use are very likely to be
      above global average rates at all stages of metal life cycles from fabrication
      onward. We show that all countries are strongly dependent on international trade
      to supply the spectrum of nonrenewable resources that modern technology requires,
      regardless of their level of development. We also find that the rate of use of
      the spectrum of metals stock is highly correlated to per capita gross domestic
      product, as well as to the Human Development Index and the Global Competitiveness
      Innovation Index. The implication is that as wealth and technology increase in
      developing countries, strong demand will be created not for a few key resources,
      but across the entire spectrum of the industrial metals. Long-term metal demand
      can be estimated given gross domestic product projections; the results suggest
      overall metal flow into use in 2050 of 5-10 times today's level should supplies
      permit.

PMID- 21098311
TI  - Maternal cardiac dysfunction and remodeling in women with preeclampsia at term.
AB  - Preeclampsia is a disease associated with significant cardiovascular morbidity
      during pregnancy and in later life. This study was designed to evaluate cardiac
      function and remodeling in preeclampsia occurring at term. This was a prospective
      case-control study of 50 term preeclampsia and 50 normal pregnancies assessed by
      echocardiography and tissue Doppler analysis. Global diastolic dysfunction was
      observed more frequently in preeclampsia versus control pregnancies (40% versus
      14%, P = 0.007). Increased cardiac work and left ventricular mass indices suggest
      that left ventricular remodeling was an adaptive response to maintain myocardial
      contractility with preeclampsia at term. Approximately 20% of patients with
      preeclampsia at term have more evident myocardial damage. Diastolic dysfunction
      usually precedes systolic dysfunction in the evolution of ischemic or
      hypertensive cardiac diseases and is of prognostic value in the prediction of
      long-term cardiovascular morbidity. The study findings also have significant
      implications for the acute medical management of preeclampsia.

PMID- 21098310
TI  - Contribution of isoprene-derived organosulfates to free tropospheric aerosol
      mass.
AB  - Recent laboratory studies have demonstrated that isoprene oxidation products can
      partition to atmospheric aerosols by reacting with condensed phase sulfuric acid,
      forming low-volatility organosulfate compounds. We have identified organosulfate
      compounds in free tropospheric aerosols by single particle mass spectrometry
      during several airborne field campaigns. One of these organosulfates is
      identified as the sulfate ester of IEPOX, a second generation oxidation product
      of isoprene. The patterns of IEPOX sulfate ester in ambient data generally
      followed the aerosol acidity and NO(x) dependence established by laboratory
      studies. Detection of the IEPOX sulfate ester was most sensitive using reduced
      ionization laser power, when it was observed in up to 80% of particles in the
      tropical free troposphere. Based on laboratory mass calibrations, IEPOX added >
      0.4% to tropospheric aerosol mass in the remote tropics and up to 20% in regions
      downwind of isoprene sources. In the southeastern United States, when acidic
      aerosol was exposed to fresh isoprene emissions, accumulation of IEPOX increased
      aerosol mass by up to 3%. The IEPOX sulfate ester is therefore one of the most
      abundant single organic compounds measured in atmospheric aerosol. Our data show
      that acidity-dependent IEPOX uptake is a mechanism by which anthropogenic SO(2)
      and marine dimethyl sulfide emissions generate secondary biogenic aerosol mass
      throughout the troposphere.

PMID- 21098312
TI  - Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm
      vasodilator responses in humans.
AB  - Cytochrome P450-derived epoxyeicosatrienoic acids are potent vasodilators in
      preclinical models and are hydrolyzed by soluble epoxide hydrolase (EPHX2).
      Associations between the EPHX2 Lys55Arg and Arg287Gln polymorphisms and
      cardiovascular disease risk have been reported; however, their impact on vascular
      function in humans has not been investigated. In 265 volunteers (198 white, 67
      black American), forearm blood flow was measured by strain-gauge venous occlusion
      plethysmography at baseline and in response to bradykinin, methacholine, and
      sodium nitroprusside. Forearm vascular resistance was calculated as mean arterial
      pressure/forearm blood flow. In white Americans, Lys55Arg genotype was associated
      with vasodilator response to bradykinin, such that forearm blood flow was
      significantly lower (P = 0.043) and forearm vascular resistance was significantly
      higher (P = 0.013) in Arg55 variant allele carriers compared to wild-type
      individuals. Significant associations were also observed with methacholine and
      sodium nitroprusside. In contrast, no relationship was observed in black
      Americans. In black Americans, Arg287Gln genotype was associated with vasodilator
      response to bradykinin. Although the difference in forearm blood flow did not
      reach statistical significance (P = 0.058), forearm vascular resistance was
      significantly lower (P = 0.037) in Gln287 variant allele carriers compared to
      wild-type individuals. Significant associations were also observed with
      methacholine and sodium nitroprusside. In white Americans, Gln287 variant allele
      carriers did not exhibit significantly higher forearm blood flow (P = 0.128) or
      lower forearm vascular resistance (P = 0.080). Genetic variation in EPHX2 is
      associated with forearm vasodilator responses in a bradykinin receptor- and
      endothelium-independent manner, suggesting an important role for soluble epoxide
      hydrolase in the regulation of vascular function in humans.

PMID- 21098314
TI  - Impact of comorbidity on chemotherapy use and outcomes in solid tumors: a
      systematic review.
AB  - BACKGROUND: The treatment of cancer in patients with comorbidities can be
      challenging as these individuals are underrepresented in clinical trials. We
      conducted a systematic review to determine the impact of comorbidity on
      chemotherapy use, delivery, tolerability, and survival among patients with solid
      tumors to summarize current data and provide recommendations for future research.
      METHODS All English-language articles from 1990 to 2009 that explored the
      association between comorbidity and chemotherapy were identified from MEDLINE and
      EMBASE. Abstracts were reviewed for eligibility, and data on study design and
      results were extracted. RESULTS: Thirty-four articles met the inclusion criteria.
      Study populations and design were heterogeneous, and the quality of reporting was
      generally poor. Most studies were retrospective (76%), were based on a cancer
      registry linked with administrative data (47%), and assessed the overall effect
      of comorbidity using an index score (76%). Sixteen studies (47%) investigated
      chemotherapy use, and 29 (85%) addressed survival. The majority reported
      decreased chemotherapy use (75%) and inferior survival (69%) for patients with
      comorbidities compared to those without. In 11 of 14 studies, inferior survival
      was independent of treatment. Of the few studies that addressed chemotherapy
      tolerability, seven of 10 reported an increased rate of severe toxicity, and
      three of five reported increased treatment delays for patients with comorbidity.
      CONCLUSION Chemotherapy use and outcomes among cancer patients with comorbidities
      are generally inferior, but the existing evidence is limited and of insufficient
      quality to determine the relationship between decreased use and inferior
      survival. Further studies that are prospective and site and stage specific are
      warranted.

PMID- 21098313
TI  - Dopamine receptors: important antihypertensive counterbalance against
      hypertensive factors.

PMID- 21098315
TI  - Complete spontaneous regression of primary diffuse large B-cell lymphoma of the
      breast.

PMID- 21098316
TI  - Evidence-based guidelines for determination of sample size and interpretation of
      the European Organisation for the Research and Treatment of Cancer Quality of
      Life Questionnaire Core 30.
AB  - PURPOSE; To use published literature to estimate large, medium, and small
      differences in quality of life (QOL) data from the European Organisation for the
      Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ
      C30). METHODS: An innovative method combining systematic review of published
      studies, expert opinions, and meta-analysis was used to estimate large, medium,
      and small differences for QLQ-C30 scores. Published mean data were identified
      from the literature. Differences (contrasts) between groups (eg, between
      treatment groups, age groups, and performance status groups) were reviewed by 34
      experts in QOL measurement and cancer treatment. The experts, blinded to actual
      QOL results, were asked to predict these differences. A large difference was
      defined as one representing unequivocal clinical relevance. A medium difference
      was defined as likely to be clinically relevant but to a lesser extent. A small
      difference was one believed to be subtle but nevertheless clinically relevant. A
      trivial difference was used to describe circumstances unlikely to have any
      clinical relevance. Actual QOL results were combined using meta-analytic
      techniques to estimate differences corresponding to small, medium, or large
      effects. RESULTS: Nine hundred eleven articles were identified, leading to 152
      relevant articles (2,217 contrasts) being reviewed by at least two experts.
      Resulting estimates from the meta-analysis varied depending on the subscale.
      Thus, the recommended minimum to detect medium differences ranges from 9
      (cognitive functioning) to 19 points (role functioning). CONCLUSION: Guidelines
      for the size of effects are provided for the QLQ-C30 subscales. These guidelines
      can be used for sample size calculations for clinical trials and can also be used
      to aid interpretation of differences in QLQ-C30 scores.

PMID- 21098318
TI  - Gene expression signature to improve prognosis prediction of stage II and III
      colorectal cancer.
AB  - PURPOSE: This study aims to develop a robust gene expression classifier that can
      predict disease relapse in patients with early-stage colorectal cancer (CRC).
      PATIENTS AND METHODS: Fresh frozen tumor tissue from 188 patients with stage I to
      IV CRC undergoing surgery was analyzed using Agilent 44K oligonucleotide arrays.
      Median follow-up time was 65.1 months, and the majority of patients (83.6%) did
      not receive adjuvant chemotherapy. A nearest mean classifier was developed using
      a cross-validation procedure to score all genes for their association with 5-year
      distant metastasis-free survival. RESULTS: An optimal set of 18 genes was
      identified and used to construct a prognostic classifier (ColoPrint). The
      signature was validated on an independent set of 206 samples from patients with
      stage I, II, and III CRC. The signature classified 60% of patients as low risk
      and 40% as high risk. Five-year relapse-free survival rates were 87.6% (95% CI,
      81.5% to 93.7%) and 67.2% (95% CI, 55.4% to 79.0%) for low- and high-risk
      patients, respectively, with a hazard ratio (HR) of 2.5 (95% CI, 1.33 to 4.73; P
      = .005). In multivariate analysis, the signature remained one of the most
      significant prognostic factors, with an HR of 2.69 (95% CI, 1.41 to 5.14; P =
      .003). In patients with stage II CRC, the signature had an HR of 3.34 (P = .017)
      and was superior to American Society of Clinical Oncology criteria in assessing
      the risk of cancer recurrence without prescreening for microsatellite instability
      (MSI). CONCLUSION: ColoPrint significantly improves the prognostic accuracy of
      pathologic factors and MSI in patients with stage II and III CRC and facilitates
      the identification of patients with stage II disease who may be safely managed
      without chemotherapy.

PMID- 21098317
TI  - Phase III, randomized study of the effects of parenteral iron, oral iron, or no
      iron supplementation on the erythropoietic response to darbepoetin alfa for
      patients with chemotherapy-associated anemia.
AB  - PURPOSE: Functional iron deficiency may impair response to erythropoiesis
      stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated
      anemia (CAA). This study evaluated whether coadministration of parenteral iron
      improves ESA efficacy in patients with CAA. PATIENTS AND METHODS: This
      prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin
      (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid
      malignancies. All patients received darbepoetin alfa once every 3 weeks and were
      randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV)
      every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks.
      RESULTS: There was no difference in the erythropoietic response rate (ie,
      proportion of patients achieving Hb >= 12 g/dL or Hb increase >= 2 g/dL from
      baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an
      erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received
      oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75).
      There were also no differences in the proportion of patients requiring red cell
      transfusions, changes in quality of life, or the dose of darbepoetin
      administered. Adverse events (AEs) tended to be more common in the IV iron arm:
      grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving
      IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46%
      (95% CI, 38% to 54%) who received oral placebo (P = .16). CONCLUSION: In patients
      with CAA, addition of IV ferric gluconate to darbepoetin failed to provide
      additional benefit compared with oral iron or oral placebo.

PMID- 21098319
TI  - Rituximab-induced immunodysregulatory ileocolitis in a patient with follicular
      lymphoma.

PMID- 21098320
TI  - Focal Langerhans cell histiocytosis (LCH) coexisting with renal cell carcinoma.

PMID- 21098322
TI  - What oncologists believe they said and what patients believe they heard: an
      analysis of phase I trial discussions.
AB  - PURPOSE; Evaluation of the communication and informed consent process in phase I
      clinical trial interviews to provide authentic, practice-based content for
      inclusion in a communication skills training intervention for health care
      professionals. PATIENTS AND METHODS: Seventeen oncologists and 52 patients from
      five United Kingdom cancer centers consented to recording of phase I trial
      discussions. Following each consultation, clinicians completed questionnaires
      indicating areas they felt they had discussed, and researchers conducted
      semistructured interviews with patients examining their recall and understanding.
      Patients and oncologists also completed the Life Orientation Test-Revised
      questionnaire, measuring predisposition toward optimism. Independent researchers
      coded the consultations identifying discussion of key information areas and how
      well this was done. Observed levels of agreement were analyzed for each
      consultation between oncologist-coder, oncologist-patient, and patient-coder
      pairs. RESULTS: In several key areas, information was either missing or had been
      explained but was interpreted incorrectly by patients. Discussion of prognosis
      was a frequent omission, with patients and coders significantly more likely to
      agree that oncologists had not discussed it (odds, 4.8; P < .001). In contrast,
      coders and oncologists were more likely to agree that alternate care plans to
      phase I trial entry had been explained (odds, 2.5; P = .023). CONCLUSION: These
      data indicate that fundamental components of communication and information
      sharing about phase I trial participation are often missing from interviews.
      Important omissions included discussion of prognosis and ensuring patient
      understanding about supportive care. These findings will inform educational
      initiatives to assist communication about phase I trials.

PMID- 21098321
TI  - Racial and ethnic disparities in risk and survival in children with
      neuroblastoma: a Children's Oncology Group study.
AB  - PURPOSE: Although health disparities are well-described for many cancers, little
      is known about racial and ethnic disparities in neuroblastoma. To evaluate
      differences in disease presentation and survival by race and ethnicity, data from
      the Children's Oncology Group (COG) were analyzed. PATIENTS AND METHODS: The
      racial/ethnic differences in clinical and biologic risk factors, and outcome of
      patients with neuroblastoma enrolled on COG ANBL00B1 between 2001 and 2009 were
      investigated. RESULTS: A total of 3,539 patients (white, 72%; black, 12%;
      Hispanic, 12%; Asian, 4%; and Native American, < 1%) with neuroblastoma were
      included. The 5-year event-free survival (EFS) rates were 67% for whites (95% CI,
      65% to 69%), 69% for Hispanics (95% CI, 63% to 74%), 62% for Asians (95% CI, 51%
      to 71%), 56% for blacks (95% CI, 50% to 62%), and 37% for Native American (95%
      CI, 17% to 58%). Blacks (P < .001) and Native Americans (P = .04) had a higher
      prevalence of high-risk disease than whites, and significantly worse EFS (P = .01
      and P = .002, respectively). Adjustment for risk group abrogated these
      differences. However, closer examination of the EFS among high-risk patients who
      remained event free for 2 years or longer, revealed a higher prevalence of late
      occurring events among blacks compared with whites (hazard ratio, 1.5; 95% CI,
      1.0 to 2.3; P = .04). CONCLUSION: Black and Native American patients with
      neuroblastoma have a higher prevalence of high-risk disease, accounting for their
      worse EFS when compared with whites. The higher prevalence of late-occurring
      events among blacks with high-risk disease suggests that this population may be
      more resistant to chemotherapy. Studies focused on delineating the genetic basis
      for the racial disparities observed in this study are planned.

PMID- 21098323
TI  - Activity of sorafenib in recurrent ovarian cancer and primary peritoneal
      carcinomatosis: a gynecologic oncology group trial.
AB  - PURPOSE Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie,
      vascular endothelial growth factor receptor [VEGFR], platelet-derived growth
      factor receptor [PDGFR], Flt3, and c-KIT). This study assessed its activity and
      tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal
      carcinomatosis (PPC). METHODS This open-label, multi-institutional, phase II
      study used a two-stage design. Eligible patients had persistent or recurrent
      OC/PPC after one to two prior cytotoxic regimens, and they experienced
      progression within 12 months of platinum-based therapy. Treatment consisted of
      sorafenib 400 mg orally twice per day. Primary end points were progression-free
      survival (PFS) at 6 months and toxicity by National Cancer Institute criteria.
      Secondary end points were tumor response and duration of PFS and overall
      survival. Biomarker analyses included measurement of ERK and b-Raf expression in
      tumors and phosphorylation of ERK (pERK) in peripheral-blood lymphocytes (PBLs)
      before and after 1 month of treatment. Results Seventy-three patients were
      enrolled, of which 71 were eligible. Fifty-nine eligible patients (83%) had
      measurable disease, and 12 (17%) had detectable disease. Significant grade 3 or 4
      toxicities included the following: rash (n = 7), hand-foot syndrome (n = 9),
      metabolic (n = 10), GI (n = 3), cardiovascular (n = 2), and pulmonary (n = 2).
      Only patients with measurable disease were used to assess efficacy. Fourteen
      survived progression free for at least 6 months (24%; 90% CI, 15% to 35%). Two
      patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease;
      30 had progressive disease; and seven could not have their tumor assessed. ERK
      and b-Raf were expressed in all tumors. Exploratory analyses indicated that pERK
      in post-treatment PBL specimens was associated with PFS. CONCLUSION Sorafenib has
      modest antitumor activity in patients with recurrent OC, but the activity was at
      the expense of substantial toxicity.

PMID- 21098325
TI  - Low-dose-rate brachytherapy for treatment of uterine didelphys malignancy.

PMID- 21098324
TI  - Integrative genomic analysis of medulloblastoma identifies a molecular subgroup
      that drives poor clinical outcome.
AB  - PURPOSE: Medulloblastomas are heterogeneous tumors that collectively represent
      the most common malignant brain tumor in children. To understand the molecular
      characteristics underlying their heterogeneity and to identify whether such
      characteristics represent risk factors for patients with this disease, we
      performed an integrated genomic analysis of a large series of primary tumors.
      PATIENTS AND METHODS: We profiled the mRNA transcriptome of 194 medulloblastomas
      and performed high-density single nucleotide polymorphism array and miRNA
      analysis on 115 and 98 of these, respectively. Non-negative matrix factorization
      based clustering of mRNA expression data was used to identify molecular subgroups
      of medulloblastoma; DNA copy number, miRNA profiles, and clinical outcomes were
      analyzed for each. We additionally validated our findings in three previously
      published independent medulloblastoma data sets. RESULTS: Identified are six
      molecular subgroups of medulloblastoma, each with a unique combination of
      numerical and structural chromosomal aberrations that globally influence mRNA and
      miRNA expression. We reveal the relative contribution of each subgroup to
      clinical outcome as a whole and show that a previously unidentified molecular
      subgroup, characterized genetically by c-MYC copy number gains and
      transcriptionally by enrichment of photoreceptor pathways and increased miR
      183~96~182 expression, is associated with significantly lower rates of event-free
      and overall survivals. CONCLUSION: Our results detail the complex genomic
      heterogeneity of medulloblastomas and identify a previously unrecognized
      molecular subgroup with poor clinical outcome for which more effective
      therapeutic strategies should be developed.

PMID- 21098326
TI  - Disease course patterns after discontinuation of bevacizumab: pooled analysis of
      randomized phase III trials.
AB  - PURPOSE: Preclinical studies have suggested accelerated tumor growth, local
      invasion, and distant metastasis after withdrawal of treatment with some
      antiangiogenic agents. To investigate whether discontinuation of bevacizumab
      treatment is associated with accelerated disease progression or increased
      mortality, we retrospectively analyzed five randomized, placebo-controlled phase
      III studies in 4,205 patients with breast, colorectal, renal, and pancreatic
      cancer. METHODS: Time from treatment discontinuation to progressive disease or
      death was analyzed in patients discontinuing bevacizumab/placebo as a result of
      adverse events (AEs). Mortality rates were assessed at 30, 60, 90, 120, 150, 180,
      and 210 days after the last bevacizumab/placebo dose in the following two groups:
      patients discontinuing bevacizumab/placebo as a result of AEs and patients
      discontinuing bevacizumab/placebo for any reason. In the same groups, time from
      treatment discontinuation to death was analyzed. Data on disease progression
      pattern were available and analyzed in four of the five studies. RESULTS: In the
      pooled analysis, median time from discontinuation as a result of AEs to
      progression/death was 3.0 months (95% CI, 2.6 to 3.8 months) for placebo and 4.0
      months (95% CI, 3.4 to 4.6 months) for bevacizumab (hazard ratio, 0.93; 95% CI,
      0.79 to 1.10). Mortality rates from 30 days to 210 days after treatment
      discontinuation and time from discontinuation to death were similar in
      bevacizumab- and placebo-treated patients. In addition, similar patterns of
      disease progression were seen in bevacizumab- and placebo-treated patients.
      CONCLUSION: This retrospective analysis of five placebo-controlled clinical
      trials does not support a decreased time to disease progression, increased
      mortality, or altered disease progression pattern after cessation of bevacizumab
      therapy.

PMID- 21098327
TI  - CCND1 and MET genomic amplification during malignant transformation of a giant
      cell tumor of bone.

PMID- 21098328
TI  - Paraneoplastic cutaneous leukocytoclastic vasculitis and iron deficiency anemia
      as the presenting features of squamous cell lung carcinoma.

PMID- 21098329
TI  - Language outcomes following risk-adapted treatments for tumors located within the
      posterior fossa.
AB  - The language skills of 4 children treated for tumors involving the cerebellum
      and/or fourth ventricle with risk-adapted treatments were compared, as a group,
      with performance of a group of control children (n = 20). The language skills of
      the individual cases were also profiled. At the group level, language skill
      failed to differentiate the 2 groups of children. At an individual level,
      however, only 1 of the 4 children treated with risk-adapted treatments presented
      with intact language skills. Variable language profiles were identified in the
      remaining 3 children. The presence of hydrocephaly was a consistent factor in
      reduced language outcomes. The findings highlight the importance of prospective
      language monitoring.

PMID- 21098330
TI  - Child neurologists as health care surrogate for imperiled children.
AB  - We explored child neurologists' attitudes toward taking on the role of health
      care surrogate for terminally ill children. Physician members of the Child
      Neurology Society were sent a 16-question survey via email. Of the assumed 1050
      recipients, 116 (11%) answered the questionnaire. Most individuals who have been
      in practice less than 11 years indicated having received formal end-of-life
      decision-making education either during medical school or residency. Conversely,
      a minority of participants who have been in practice more than 11 years indicated
      having received such education. Regardless of years in practice, 54% (n = 61 of
      112) of participants would feel at least ''somewhat comfortable'' independently
      making life-limiting decisions for imperiled patients. The number increased to
      80% if the decision were made within the context of a multidisciplinary team.
      Taking our data and the experience published by others into consideration, we
      suggest a method for establishing such a team.

PMID- 21098331
TI  - Sleep behavior disturbances in rolandic epilepsy.
AB  - The relationship between specific epilepsy syndromes and particular sleep
      symptoms has not been well delineated. The authors' aim was to test the
      hypothesis that children with rolandic epilepsy exhibit more frequent sleep
      problems and daytime sleepiness compared with children without epilepsy. They
      compared parent-reported sleep behaviors of 43 children with rolandic epilepsy
      aged 6 to 16 years recruited from 5 US pediatric neurology centers with a
      historical reference and sleep clinic sample using the Child Sleep Habits
      Questionnaire. The authors compared the differences in mean frequency of sleep
      problems and patterns. Total Children's Sleep Habits Questionnaire scores were
      significantly higher (P < .001) in the rolandic epilepsy sample than reference.
      Parents of children with rolandic epilepsy reported a significantly shorter sleep
      duration (P < .006), more frequent parasomnias (P < .008), and increased daytime
      sleepiness (P < .001). Thus, parents of children with rolandic epilepsy reported
      more problematic sleep and daytime impairment compared with a reference sample of
      children.

PMID- 21098332
TI  - Acute postinfectious movement and psychiatric disorders in children and
      adolescents.
AB  - The authors report 4 children and adolescents who had the acute onset of a
      movement and psychiatric disorder after a febrile illness. The differential
      diagnosis includes poststreptococcal syndromes (Sydenham chorea, pediatric
      autoimmune neuropsychiatric disorders associated with streptococcal infection
      [PANDAS], acute disseminated encephalomyelitis) and other postinfectious
      conditions. Their cases illustrate difficulties in making an accurate diagnosis
      and determining proper therapy and they recommend a standard diagnostic approach.
      More research is needed to clarify the nature, causes, and appropriate treatment
      of these types of disorders.

PMID- 21098333
TI  - Meeting the psychosocial needs of sibling survivors: a family systems approach.
AB  - Although increasing numbers of studies have examined late effects in survivors,
      there is a paucity of long-term outcome studies in their siblings, so-called
      sibling survivors. Our aim was to provide a review of publications relevant to
      survivorship and its impact on the long-term psychosocial health of sibling
      survivors using a family systems framework. A review of publications identified
      19 articles that reported findings suggesting that aspects of psychosocial health
      may be impaired in sibling survivors. Baseline functioning of sibling survivors
      may be altered at the start of survivorship secondary to apprehension, memories,
      and emotions. New demands are placed on sibling survivors, including doubts,
      questions, and worries due to survivorship. Survivor disfigurement may also place
      demands on sibling survivors associated with behavioral problems. Associated with
      these changes, there may be alterations in adaptation, including depression,
      somatic complaints, and posttraumatic stress symptoms. Sibling survivors may also
      report health risk behaviors and decreased vitality. Identification of the impact
      of survivorship on the long-term psychosocial health of sibling survivors may
      help ensure the long-term psychosocial health of all survivors.

PMID- 21098334
TI  - Understanding growth failure in children with homozygous sickle-cell disease.
AB  - Sickle-cell disease is the most prevalent genetic hematologic condition in the
      United States. Numerous studies have demonstrated poor growth and delayed
      maturation in children with homozygous sickle-cell disease; however, the
      pathophysiology remains inadequately understood. Affected children have normal
      weight and length at birth, and then around 6 months of age their growth patterns
      begin to diverge from the norm. The growth deficits experienced by these children
      remain a problem with clinical significance and intangible consequences. A review
      of literature has provided insight into the multifactorial basis of the growth
      failure experienced by this population. It is important that nurses and health
      care providers are familiar with the growth patterns unique to sickle-cell
      disease and recognize their role in clinical practice.

PMID- 21098335
TI  - Exploring family-centered care among pediatric oncology nurses.
AB  - Family-centered care (FCC) is important within pediatric oncology nursing.
      However, pediatric oncology nurses often face challenges and barriers when
      attempting to provide FCC. The purpose of this study was to understand the
      experiences of pediatric oncology nurses in relation to FCC; identify how
      pediatric oncology nurses implemented FCC into their practice; identify what
      facilitated and enabled pediatric oncology nurses to implement FCC; and discern
      the barriers and challenges that were present in their setting when implementing
      FCC. A qualitative approach utilizing person-centered interviewing was used to
      collect data. Nurses (N=20) from a western Canadian children's hospital were
      recruited through purposeful convenience sampling and were then interviewed. Five
      major themes were identified from the data set: Hospital support f FCC, How
      participants defined FCC, Establishing FCC, Enhancing FCC, and Barriers and
      Challenges to providing FCC. Recommendations for future research and implications
      for practice and education are offered.

PMID- 21098336
TI  - Endogenous versus tumor-specific host response to breast carcinoma: a study of
      stromal response in synchronous breast primaries and biopsy site changes.
AB  - PURPOSE: We recently described two types of stromal response in breast cancer
      derived from gene expression studies of tenosynovial giant cell tumors and
      fibromatosis. The purpose of this study is to elucidate the basis of this stromal
      response--whether they are elicited by individual tumors or whether they
      represent an endogenous host reaction produced by the patient. EXPERIMENTAL
      DESIGN: Stromal signatures from patients with synchronous dual primaries were
      analyzed by immunohistochemistry on a tissue microarray (n = 26 pairs) to
      evaluate the similarity of stromal responses in different tumors within the same
      patient. We also characterized the extent to which the stromal signatures were
      conserved between stromal response to injury compared to the stromal response to
      carcinoma using gene expression profiling and tissue microarray
      immunohistochemistry. RESULTS: The two stromal response signatures showed
      divergent associations in synchronous primaries: the DTF fibroblast response is
      more likely to be similar in a patient with multiple breast primaries
      (permutation analysis P = 0.0027), whereas CSF1 macrophage response shows no
      significant concordance in separate tumors within a given patient. The DTF
      fibroblast signature showed more concordance across normal, cancer, and biopsy
      site samples from within a patient, than across normal, cancer, and biopsy site
      samples from a random group of patients, whereas the CSF1 macrophage response did
      not. CONCLUSIONS: The results suggest that the DTF fibroblast response is host
      specific, whereas the CSF1 response may be tumor-elicited. Our findings provide
      further insight into stromal response and may facilitate the development of
      therapeutic strategies to target particular stromal subtypes.

PMID- 21098337
TI  - Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia
      chromosome-positive leukemia.
AB  - Beginning with imatinib a decade ago, therapy based on targeted inhibition of the
      BCR-ABL kinase has greatly improved the prognosis for chronic myeloid leukemia
      (CML) patients. The recognition that some patients experience relapse due to
      resistance-conferring point mutations within BCR-ABL sparked the development of
      the second-generation ABL kinase inhibitors nilotinib and dasatinib.
      Collectively, these drugs target most resistant BCR-ABL mutants, with the
      exception of BCR-ABL(T315I). A third wave of advances is now cresting in the form
      of ABL kinase inhibitors whose target profile encompasses BCR-ABL(T315I). The
      leading third-generation clinical candidate for treatment-refractory CML,
      including patients with the T315I mutation, is ponatinib (AP24534), a pan-BCR-ABL
      inhibitor that has entered pivotal phase 2 testing. A second inhibitor with
      activity against the BCR-ABL(T315I) mutant, DCC-2036, is in phase 1 clinical
      evaluation. We provide an up-to-date synopsis of BCR-ABL signaling pathways,
      highlight new findings on mechanisms underlying BCR-ABL mutation acquisition and
      disease progression, discuss the use of nilotinib and dasatinib in a first-line
      capacity, and evaluate ponatinib, DCC-2036, and other ABL kinase inhibitors with
      activity against BCR-ABL(T315I) in the development pipeline.

PMID- 21098338
TI  - HGF rescues colorectal cancer cells from EGFR inhibition via MET activation.
AB  - PURPOSE: Cetuximab, an antibody targeting the epidermal growth factor receptor
      (EGFR), is active in colorectal cancer (CRC). However, response rates range from
      only 10% to 20%. Here, we investigate hepatocyte growth factor (HGF)-dependent
      mesenchymal-epithelial transition factor (MET) activation as a mediator of
      cetuximab resistance through signal diversification in CRC cell lines.
      EXPERIMENTAL DESIGN: DiFi, GEO, and LIM1215 cells were treated with varying
      concentrations and combinations of EGF, HGF, cetuximab, and PHA-665752 (a highly
      specific MET kinase inhibitor). Biological end points included proliferation,
      cell cycle arrest, and apoptosis. Proliferation was measured using WST-1 assays
      and synergy investigated via isobolograms. Expression and signaling were examined
      using immunoblotting. RESULTS: EGFR and MET are coexpressed in these CRC cell
      lines, and dual receptor activation synergistically increased proliferation.
      Cetuximab inhibited cell growth by 60%-80% with an associated dephosphorylation
      of EGFR, MAPK, and/or AKT. Addition of HGF to cetuximab-treated cells
      phosphorylated MET, but not EGFR or ErbB3, restimulated the MAPK and AKT
      pathways, restored cell proliferation, and rescued cells from G1 arrest and
      apoptosis. Importantly, this effect could be abrogated by inhibiting MET
      activation with PHA-665752 or by downregulating MET expression with RNAi.
      CONCLUSIONS: HGF-induced MET activation is a novel mechanism of cetuximab
      resistance in CRC. Inhibition of the HGF-MET pathway may improve response to EGFR
      inhibitors in CRC, and combination therapy should be further investigated.

PMID- 21098339
TI  - Green tea extract-induced lethal toxicity in fasted but not in nonfasted dogs.
AB  - Recent chronic toxicity studies performed on green tea extracts in fasted dogs
      have revealed some unique dose-limiting lethal liver, gastrointestinal, and renal
      toxicities. Key findings included necrosis of hepatic cells, gastrointestinal
      epithelia and renal tubules, atrophy of reproductive organs, atrophy and necrosis
      of hematopoietic tissues, and associated hematological changes. The polyphenol
      cachetins (a mixture of primarily epigallocatechin gallate [>=55%]; plus up to
      10% each of epigallocatechin, epicatechin, and epigallocatechin gallate) appeared
      to be the causative agents for the observed toxicities because they are the
      active ingredients of green tea extract studied. Conduct of the study in
      nonfasted dogs under the same testing conditions and dose levels showed
      unremarkable results. Assuming both studies were valid, at the identified no
      observed adverse effect levels (NOAEL) of each study, systemic exposures (based
      on area under the curve [AUC]) were actually lower in fasted than nonfasted dogs,
      suggesting that fasting may have rendered the target organ systems potentially
      more vulnerable to the effects of green tea extract. The toxicity mechanisms that
      produced lethality are not known, but the results are scientifically intriguing.
      Because tea drinking has become more popular in the United States and abroad, the
      mode of action and site of action of green tea extract-induced lethal toxicities
      during fasting and the role of other phytochemical components of Folia Camellia
      sinensis (including nonpolyphenol fractions, which are often consumed when whole
      leaf products are presented) warrant further investigation.

PMID- 21098340
TI  - Effect of music-based multitask training on gait, balance, and fall risk in
      elderly people: a randomized controlled trial.
AB  - BACKGROUND: Falls occur mainly while walking or performing concurrent tasks. We
      determined whether a music-based multitask exercise program improves gait and
      balance and reduces fall risk in elderly individuals. METHODS: We conducted a 12
      month randomized controlled trial involving 134 community-dwelling individuals
      older than 65 years, who are at increased risk of falling. They were randomly
      assigned to an intervention group (n = 66) or a delayed intervention control
      group scheduled to start the program 6 months later (n = 68). The intervention
      was a 6-month multitask exercise program performed to the rhythm of piano music.
      Change in gait variability under dual-task condition from baseline to 6 months
      was the primary end point. Secondary outcomes included changes in balance,
      functional performances, and fall risk. RESULTS: At 6 months, there was a
      reduction in stride length variability (adjusted mean difference, -1.4%; P <
      .002) under dual-task condition in the intervention group, compared with the
      delayed intervention control group. Balance and functional tests improved
      compared with the control group. There were fewer falls in the intervention group
      (incidence rate ratio, 0.46; 95% confidence interval, 0.27-0.79) and a lower risk
      of falling (relative risk, 0.61; 95% confidence interval, 0.39-0.96). Similar
      changes occurred in the delayed intervention control group during the second 6
      month period with intervention. The benefit of the intervention on gait
      variability persisted 6 months later. CONCLUSION: In community-dwelling older
      people at increased risk of falling, a 6-month music-based multitask exercise
      program improved gait under dual-task condition, improved balance, and reduced
      both the rate of falls and the risk of falling. Trial Registration
      clinicaltrials.gov Identifier: NCT01107288.

PMID- 21098341
TI  - Serum alpha-carotene concentrations and risk of death among US Adults: the Third
      National Health and Nutrition Examination Survey Follow-up Study.
AB  - BACKGROUND: Much research has been conducted relating total carotenoids--and beta
      carotene in particular--to risk of cancer and cardiovascular disease (CVD).
      Limited data are emerging to implicate the important role of alpha-carotene in
      the development of CVD or cancer. METHODS: We assessed the direct relationship
      between alpha-carotene concentrations and risk of death among 15,318 US adults 20
      years and older who participated in the Third National Health and Nutrition
      Examination Survey Follow-up Study. We used Cox proportional hazard regression
      analyses to estimate the relative risk for death from all causes and selected
      causes associated with serum alpha-carotene concentrations. RESULTS: Compared
      with participants with serum alpha-carotene concentrations of 0 to 1 MUg/dL (to
      convert to micromoles per liter, multiply by 0.01863), those with higher serum
      levels had a lower risk of death from all causes (P < .001 for linear trend): the
      relative risk for death was 0.77 (95% confidence interval, 0.68-0.87) among those
      with alpha-carotene concentrations of 2 to 3 MUg/dL, 0.73 (0.65-0.83) among those
      with concentrations of 4 to 5 MUg/dL, 0.66 (0.55-0.79) among those with
      concentrations of 6 to 8 MUg/dL, and 0.61 (0.51-0.73) among those with
      concentrations of 9 MUg/dL or higher after adjustment for potential confounding
      variables. We also found significant associations between serum alpha-carotene
      concentrations and risk of death from CVD (P = .007), cancer (P = .02), and all
      other causes (P < .001). The association between serum alpha-carotene
      concentrations and risk of death from all causes was significant in most
      subgroups stratified by demographic characteristics, lifestyle habits, and health
      risk factors. CONCLUSIONS: Serum alpha-carotene concentrations were inversely
      associated with risk of death from all causes, CVD, cancer, and all other causes.
      These findings support increasing fruit and vegetable consumption as a means of
      preventing premature death.

PMID- 21098342
TI  - Inclusion of training patients in US Food and Drug Administration premarket
      approval cardiovascular device studies.
AB  - BACKGROUND: Training patients are the first individuals in whom a physician uses
      an investigational device. There is great variability in the use of data from
      training patients in the absence of guidelines. The prevalence and extent of data
      reporting from training patients in cardiovascular device studies submitted for
      US Food and Drug Administration (FDA) approval has not been characterized.
      METHODS: Information on training patients was abstracted from the Summary of
      Safety and Effectiveness Data summarizing cardiovascular device premarket
      applications approved by the FDA from 2000 through 2007. We examined the numbers
      and characteristics of training patients and the inclusion of their results in
      end-point analyses. RESULTS: There were 78 cardiovascular device summaries in
      this 8-year period, of which 17 (22%) involved training patients. Of the 123
      studies in the summaries, 20 (16%) used training patients. All studies excluded
      training patients from efficacy analyses and 19 of 20 (95%) excluded them from
      safety analyses. Sixteen of 20 (80%) did not provide any outcome data, and 15 of
      20 (75%) did not check for outcome differences between training and nontraining
      treatment patients. Eighteen of 20 (90%) did not provide demographic information
      on training patients, and 14 of 20 (70%) did not prespecify guidelines for their
      enrollment. CONCLUSIONS: Training patients comprise a considerable proportion of
      patients receiving investigational cardiovascular devices, but their results are
      excluded from FDA submissions. Their exclusion from analyses means that safety
      and efficacy outcomes may look better than actual results. Guidelines on the use
      and inclusion of results for training patients would improve accuracy on results
      reporting.

PMID- 21098343
TI  - Patient education to prevent falls among older hospital inpatients: a randomized
      controlled trial.
AB  - BACKGROUND: Falls are a common adverse event during hospitalization of older
      adults, and few interventions have been shown to prevent them. METHODS: This
      study was a 3-group randomized trial to evaluate the efficacy of 2 forms of
      multimedia patient education compared with usual care for the prevention of in
      hospital falls. Older hospital patients (n = 1206) admitted to a mixture of acute
      (orthopedic, respiratory, and medical) and subacute (geriatric and
      neurorehabilitation) hospital wards at 2 Australian hospitals were recruited
      between January 2008 and April 2009. The interventions were a multimedia patient
      education program based on the health-belief model combined with trained health
      professional follow-up (complete program), multi-media patient education
      materials alone (materials only), and usual care (control). Falls data were
      collected by blinded research assistants by reviewing hospital incident reports,
      hand searching medical records, and conducting weekly patient interviews.
      RESULTS: Rates of falls per 1000 patient-days did not differ significantly
      between groups (control, 9.27; materials only, 8.61; and complete program, 7.63).
      However, there was a significant interaction between the intervention and
      presence of cognitive impairment. Falls were less frequent among cognitively
      intact patients in the complete program group (4.01 per 1000 patient-days) than
      among cognitively intact patients in the materials-only group (8.18 per 1000
      patient-days) (adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93])
      and control group (8.72 per 1000 patient-days) (adjusted hazard ratio, 0.43; 95%
      confidence interval, 0.24-0.78). CONCLUSION: Multimedia patient education with
      trained health professional follow-up reduced falls among patients with intact
      cognitive function admitted to a range of hospital wards. Trial Registration
      anzctr.org.au Identifier: ACTRN12608000015347.

PMID- 21098344
TI  - Predicting incident atrial fibrillation: an important step toward primary
      prevention.

PMID- 21098345
TI  - Subclinical thyroid dysfunction and incident hip fracture in older adults.
AB  - BACKGROUND: Subclinical thyroid dysfunction is common in older adults and affects
      bone metabolism, but its effects on fracture risk have not been reported. We
      sought to determine prospectively whether older men and women with subclinical
      hyperthyroidism or hypothyroidism have an increased risk of hip fracture.
      METHODS: Prospective cohort of 3567 US community-dwelling adults, 65 years or
      older, with biochemically defined subclinical thyroid dysfunction or euthyroidism
      was enrolled from June 10, 1989, through May 30, 1990, and followed up through
      2004. Main outcome measures included incidence and hazard ratios (HRs), with 95%
      confidence intervals (CIs), of confirmed incident hip fractures for groups with
      subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as
      defined at baseline. RESULTS: During 39 952 person-years (median follow-up, 13
      years), hip fracture incidence (per 1000 men-years) was 13.65 in men with
      subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical
      hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n =
      1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of
      2.31 (95% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99
      11.30). After excluding those with baseline use of thyroid-altering medications,
      men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95% CI,
      1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27
      4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with
      subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical
      hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n =
      1694). No clear association between subclinical dysfunction and fracture was
      observed in women. CONCLUSIONS: Older men with subclinical hyperthyroidism or
      hypothyroidism are at increased risk for hip fracture. Whether treatment of the
      subclinical syndrome reduces this risk is unknown.

PMID- 21098346
TI  - Bidirectional association between depression and type 2 diabetes mellitus in
      women.
AB  - BACKGROUND: Although it has been hypothesized that the diabetes-depression
      relation is bidirectional, few studies have addressed this hypothesis in a
      prospective setting. METHODS: A total of 65 381 women aged 50 to 75 years in 1996
      were observed until 2006. Clinical depression was defined as having diagnosed
      depression or using antidepressants, and depressed mood was defined as having
      clinical depression or severe depressive symptoms, ie, a 5-item Mental Health
      Index (MHI-5) score of 52 or less. Self-reported type 2 diabetes mellitus was
      confirmed by means of a supplementary questionnaire validated by medical record
      review. RESULTS: During 10 years of follow-up (531 097 person-years), 2844
      incident cases of type 2 diabetes mellitus were documented. Compared with
      referents (MHI-5 score of 86-100) who had the best depressive symptom scores,
      participants with increased severity of symptoms (MHI-5 scores of 76-85 or 53-75,
      or depressed mood) showed a monotonic elevated risk of developing type 2 diabetes
      (P for trend = .002 in the multivariable-adjusted model). The relative risk for
      individuals with depressed mood was 1.17 (95% confidence interval [CI], 1.05
      1.30) after adjustment for various covariates, and participants using
      antidepressants were at a particularly higher relative risk (1.25; 95% CI, 1.10
      1.41). In a parallel analysis, 7415 cases of incident clinical depression were
      documented (474 722 person-years). Compared with nondiabetic subjects, those with
      diabetes had a relative risk (95% CI) of developing clinical depression after
      controlling for all covariates of 1.29 (1.18-1.40), and it was 1.25 (1.09-1.42),
      1.24 (1.09-1.41), and 1.53 (1.26-1.85) in diabetic subjects without medications,
      with oral hypoglycemic agents, and with insulin therapy, respectively. These
      associations remained significant after adjustment for diabetes-related
      comorbidities. CONCLUSION: Our results provide compelling evidence that the
      diabetes-depression association is bidirectional.

PMID- 21098347
TI  - Metformin use and mortality among patients with diabetes and atherothrombosis.
AB  - BACKGROUND: Metformin is recommended in type 2 diabetes mellitus because it
      reduced mortality among overweight participants in the United Kingdom Prospective
      Diabetes Study when used mainly as a means of primary prevention. However,
      metformin is often not considered in patients with cardiovascular conditions
      because of concerns about its safety. METHODS: We assessed whether metformin use
      was associated with a difference in mortality among patients with
      atherothrombosis. The study sample comprised 19 691 patients having diabetes with
      established atherothrombosis participating in the Reduction of Atherothrombosis
      for Continued Health (REACH) Registry between December 1, 2003, and December 31,
      2004, treated with or without metformin. Multivariable adjustment and propensity
      score were used to account for baseline differences. The main outcome measure was
      2-year mortality. RESULTS: The mortality rates were 6.3% (95% confidence interval
      [CI], 5.2%-7.4%) with metformin and 9.8% 8.4%-11.2%) without metformin; the
      adjusted hazard ratio (HR) was 0.76 (0.65-0.89; P < .001). Association with lower
      mortality was consistent among subgroups, noticeably in patients with a history
      of congestive heart failure (HR, 0.69; 95% CI, 0.54-0.90; P = .006), patients
      older than 65 years (0.77; 0.62-0.95; P = .02), and patients with an estimated
      creatinine clearance of 30 to 60 mL/min/1.73 m(2) (0.64; 95% CI, 0.48-0.86; P =
      .003) (to convert creatinine clearance to mL/s/m(2), multiply by 0.0167).
      CONCLUSIONS: Metformin use may decrease mortality among patients with diabetes
      when used as a means of secondary prevention, including subsets of patients in
      whom metformin use is not now recommended. Metformin use should be tested
      prospectively in this population to confirm its effect on survival.

PMID- 21098348
TI  - Renal ultrasonography in the evaluation of acute kidney injury: developing a risk
      stratification framework.
AB  - BACKGROUND: In adult inpatients with acute kidney injury (AKI), clinicians
      routinely order a renal ultrasonography (RUS) study. It is unclear how often this
      test provides clinically useful information. METHODS: Cross-sectional study,
      including derivation and validation samples, of 997 US adults admitted to Yale
      New Haven Hospital from January 2005 to May 2009, who were diagnosed as having
      AKI and who underwent RUS to evaluate elevated creatinine level. Pregnant women,
      renal transplant recipients, and patients with recently diagnosed hydronephrosis
      (HN) were excluded. Demographic and clinical characteristics were abstracted from
      the medical records. A multivariable logistic regression model was developed to
      create risk strata for HN and HN requiring an intervention (HNRI); a separate
      sample was used for validation. The frequency of incidental findings on RUS was
      assessed for each stratum. RESULTS: In a derivation sample of 200 patients, 7
      factors were found to be associated with HN: history of HN; recurrent urinary
      tract infections; diagnosis consistent with obstruction; nonblack race; and
      absence of the following: exposure to nephrotoxic medications, congestive heart
      failure, or prerenal AKI. Among 797 patients in the validation sample (mean age,
      65.6 years), 10.6% had HN and 3.3% had HNRI. Of 223 patients in the low-risk
      group, 7 (3.1%) had HN and 1 (0.4%) had HNRI (223 patients needed to be screened
      to find 1 case of HNRI). In this group, there were 0 incidental findings on RUS
      unknown to the clinical team. In the higher-risk group, 15.7% had HN and 4.7% had
      HNRI. CONCLUSION: In adult inpatients with AKI, specific factors can identify
      patients unlikely to have HN or HNRI on RUS.

PMID- 21098349
TI  - Curbing the use of ultrasonography in the diagnosis of acute kidney injury: Penny
      wise or pound foolish?: Comment on "Renal ultrasonography in the evaluation of
      acute kidney injury".

PMID- 21098352
TI  - Health care use and decision making among lower-income families in high
      deductible health plans.
AB  - BACKGROUND: Lower-income families may face unique challenges in high-deductible
      health plans (HDHPs). METHODS: We administered a cross-sectional survey to a
      stratified random sample of families in a New England health plan's HDHP with at
      least $500 in annualized out-of-pocket expenditures. Lower-income families were
      defined as having incomes that were less than 300% of the federal poverty level.
      Primary outcomes were cost-related delayed or foregone care, difficulty
      understanding plans, unexpected costs, information-seeking, and likelihood of
      families asking their physician about hypothetical recommended services subject
      to the plan deductible. Multivariate logistic regression was used to control for
      potential confounders of associations between income group and primary outcomes.
      RESULTS: Lower-income families (n = 141) were more likely than higher-income
      families (n = 273) to report cost-related delayed or foregone care (57% vs 42%;
      adjusted odds ratio [AOR], 1.81; 95% confidence interval [CI], 1.15-2.83]). There
      were no differences in plan understanding, unexpected costs, or information
      seeking by income. Lower-income families were more likely than others to say they
      would ask their physician about a $100 blood test (79% vs 63%; AOR, 1.97; 95% CI,
      1.18-3.28) or a $1000 screening colonoscopy (89% vs 80%; AOR, 2.04; 95% CI, 1.06
      3.93) subject to the plan deductible. CONCLUSIONS: Lower-income families with out
      of-pocket expenditures in an HDHP were more likely than higher-income families to
      report cost-related delayed or foregone care but did not report more difficulty
      understanding or using their plans, and might be more likely to question services
      requiring out-of-pocket expenditures. Policymakers and physicians should consider
      focused monitoring and benefit design modifications to support lower-income
      families in HDHPs.

PMID- 21098350
TI  - Validation of an atrial fibrillation risk algorithm in whites and African
      Americans.
AB  - BACKGROUND: We sought to validate a recently published risk algorithm for
      incident atrial fibrillation (AF) in independent cohorts and other racial groups.
      METHODS: We evaluated the performance of a Framingham Heart Study (FHS)-derived
      risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764
      participants) and 2 geographically and racially diverse cohorts in the age range
      45 to 95 years: AGES (the Age, Gene/Environment Susceptibility-Reykjavik Study)
      (n = 4238) and CHS (the Cardiovascular Health Study) (n = 5410, of whom 874
      [16.2%] were African Americans). The risk algorithm included age, sex, body mass
      index, systolic blood pressure, electrocardiographic PR interval, hypertension
      treatment, and heart failure. RESULTS: We found 1359 incident AF events in 100
      074 person-years of follow-up. Unadjusted 5-year event rates differed by cohort
      (AGES, 12.8 cases/1000 person-years; CHS whites, 22.7 cases/1000 person-years;
      and FHS, 4.5 cases/1000 person-years) and by race (CHS African Americans, 18.4
      cases/1000 person-years). The strongest risk factors in all samples were age and
      heart failure. The relative risks for incident AF associated with risk factors
      were comparable across cohorts and race groups. After recalibration for baseline
      incidence and risk factor distribution, the Framingham algorithm, reported in C
      statistic, performed reasonably well in all samples: AGES, 0.67 (95% confidence
      interval [CI], 0.64-0.71); CHS whites, 0.68 (95% CI, 0.66-0.70); and CHS African
      Americans, 0.66 (95% CI, 0.61-0.71). Risk factors combined in the algorithm
      explained between 47.0% (AGES) and 63.6% (FHS) of the population-attributable
      risk. CONCLUSIONS: Risk of incident AF in community-dwelling whites and African
      Americans can be assessed reliably by routinely available and potentially
      modifiable clinical variables. Seven risk factors accounted for up to 64% of
      risk.

PMID- 21098353
TI  - High-deductible plans: What if you can't afford your share?: Comment on "Health
      care use and decision-making among lower-income families in high-deductible
      health plans".

PMID- 21098355
TI  - Testing for the presence of positive-outcome bias in peer review: a randomized
      controlled trial.
AB  - BACKGROUND: If positive-outcome bias exists, it threatens the integrity of
      evidence-based medicine. METHODS: We sought to determine whether positive-outcome
      bias is present during peer review by testing whether peer reviewers would (1)
      recommend publication of a "positive" version of a fabricated manuscript over an
      otherwise identical "no-difference" version, (2) identify more purposefully
      placed errors in the no-difference version, and (3) rate the "Methods" section in
      the positive version more highly than the identical "Methods" section in the no
      difference version. Two versions of a well-designed randomized controlled trial
      that differed only in the direction of the finding of the principal study end
      point were submitted for peer review to 2 journals in 2008-2009. Of 238 reviewers
      for The Journal of Bone and Joint Surgery and Clinical Orthopaedics and Related
      Research randomly allocated to review either a positive or a no-difference
      version of the manuscript, 210 returned reviews. RESULTS: Reviewers were more
      likely to recommend the positive version of the test manuscript for publication
      than the no-difference version (97.3% vs 80.0%, P < .001). Reviewers detected
      more errors in the no-difference version than in the positive version (0.85 vs
      0.41, P < .001). Reviewers awarded higher methods scores to the positive
      manuscript than to the no-difference manuscript (8.24 vs 7.53, P = .005),
      although the "Methods" sections in the 2 versions were identical. CONCLUSIONS:
      Positive-outcome bias was present during peer review. A fabricated manuscript
      with a positive outcome was more likely to be recommended for publication than
      was an otherwise identical no-difference manuscript.

PMID- 21098354
TI  - National estimates of emergency department visits for hemorrhage-related adverse
      events from clopidogrel plus aspirin and from warfarin.
AB  - BACKGROUND: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin is a
      well-established antithrombotic strategy, with hemorrhage being the chief adverse
      event (AE) of concern. Outside of clinical trials, few published data describe
      the magnitude and nature of hemorrhage-related AEs from DAT. METHODS: To estimate
      the numbers and rates of emergency department (ED) visits for hemorrhage-related
      AEs (hemorrhage or evaluation for potential hemorrhage) from DAT in the United
      States and put them in the context of those from warfarin, we analyzed AEs from
      the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event
      Surveillance project, 2006-2008, and outpatient prescribing from the National
      Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care
      Survey, 2006-2007. RESULTS: Based on 384 cases, there were an estimated 7654 (95%
      confidence interval [CI], 3325-11 983) ED visits annually for hemorrhage-related
      AEs from DAT compared with 2926 cases and an estimated 60 575 (36 117-85 033) ED
      visits from warfarin. Approximately 60% of ED visits for DAT consisted of
      epistaxis or other minor hemorrhages (eg, bleeding from small cuts). The risk of
      hospitalization for ED visits involving acute hemorrhages was not significantly
      different between DAT and warfarin (risk ratio, 0.73; 95% CI, 0.38-1.08). The
      estimated rate of ED visits involving acute hemorrhages from DAT was 1.2 per 1000
      outpatient prescription visits vs 2.5 per 1000 outpatient prescription visits for
      warfarin (risk ratio, 0.49; 95% CI, 0.15-0.83). CONCLUSIONS: These findings
      indicate that the acute hemorrhagic risk with DAT is clinically significant and
      reinforce the importance of practitioners and patients recognizing and
      anticipating this risk.

PMID- 21098356
TI  - Predicting hip and major osteoporotic fractures using administrative data.

PMID- 21098357
TI  - Early ambulation and length of stay in older adults hospitalized for acute
      illness.

PMID- 21098359
TI  - Prasugrel and cancer.

PMID- 21098358
TI  - Platelet inhibition and cancer promotion.

PMID- 21098360
TI  - First oral thrombin inhibitor enters market: drug does not require clinicians to
      monitor INR.

PMID- 21098363
TI  - Hospitals weather recovery audits.

PMID- 21098364
TI  - January deadline looms for DME suppliers.

PMID- 21098366
TI  - Pharmacist-driven seasonal influenza immunization program for health care
      workers.

PMID- 21098367
TI  - Manufacturers' recommendations for handling spilled hazardous drugs.

PMID- 21098368
TI  - In vitro stability of polyurethane and silicone feeding tubes exposed to fish
      oil.

PMID- 21098369
TI  - Efficient dispensing of medications by a traveling health care team.

PMID- 21098370
TI  - Surviving and thriving in tough economic times.

PMID- 21098371
TI  - Have you ever thought about a career in small and rural hospitals?

PMID- 21098372
TI  - Open letter to administrators of rural hospitals.

PMID- 21098373
TI  - Doripenem: a new carbapenem antibiotic.
AB  - PURPOSE: The chemistry, pharmacology, antimicrobial activity, pharmacokinetics,
      pharmacodynamics, efficacy and safety in humans, and formulary considerations of
      doripenem are reviewed. SUMMARY: Doripenem, a member of the beta-lactam class of
      antibiotics, is the newest addition to the carbapenems. It exhibits concentration
      independent bactericidal activity against gram-positive bacteria; enteric and
      nonenteric gram-negative bacteria, including extended-spectrum beta-lactamase
      producing strains; and anaerobic pathogens. Doripenem was found to be noninferior
      to meropenem in the treatment of complicated intraabdominal infections and
      noninferior to levofloxacin in the treatment of complicated urinary tract
      infections including pyelonephritis and was granted marketing approval by the
      Food and Drug Administration for these two indications. Doripenem was also found
      to be noninferior to imipenem in the treatment of ventilator-associated pneumonia
      and noninferior to piperacillin-tazobactam in the treatment of hospital-acquired
      pneumonia. It has a favorable safety profile, with gastrointestinal complaints
      and headache being the most common adverse effects and allergic reactions the
      most serious adverse effects. Doripenem has a relatively low potential to induce
      seizures. The only known clinically relevant drug interaction is that
      coadministration with valproic acid may result in reductions of valproic acid
      serum concentrations. As with most renally eliminated antibiotics, the dose of
      doripenem should be adjusted according to kidney function. CONCLUSION: Doripenem
      is an injectable carbapenem antibiotic with a spectrum of activity comparable to
      that of imipenem and meropenem. Its safety is similar to that of other
      carbapenems.

PMID- 21098374
TI  - Risk of cancer in patients receiving insulin glargine.
AB  - PURPOSE: The risk of malignancy in patients using insulin glargine was evaluated.
      SUMMARY: Patients with diabetes mellitus have increased rates of cancers
      including breast, colon, and pancreatic cancers. Since nondiabetic patients with
      increased levels of insulin have similar rates of the same cancers,
      hyperinsulinemia could be key. Normally, insulin produces metabolic effects and
      insulin-like growth factor-I (IGF-I) produces mitogenic effects. Since the
      molecules are structurally similar, it is possible for insulin to act like IGF-I,
      promoting mitogenicity. Concern that insulin may promote the growth of some
      cancers is heightened with insulin analogues, since changing the structure of
      human insulin could produce molecules with increased mitogenic potential. In
      vivo, insulin glargine has been shown to have greater mitogenic potential than
      human insulin. It is unknown whether this occurs in vitro, because the insulin
      glargine molecule is transformed once injected. Studies published in 2009 suggest
      that patients on insulin glargine could be at greater risk for cancer than
      patients on other antidiabetes therapies, but the trial results are conflicting.
      In response, the Food and Drug Administration, American Diabetes Association,
      American Association of Clinical Endocrinologists, and European Association for
      the Study of Diabetes have formally stated that patients should continue to use
      insulin glargine until more information is available. CONCLUSION: Studies on the
      relationship between insulin glargine and cancer have been inconclusive.

PMID- 21098375
TI  - Probable interaction between warfarin and bee pollen.
AB  - PURPOSE: A probable interaction between warfarin and honeybee-collected pollen is
      reported. SUMMARY: A 71-year-old Caucasian man arrived at an anticoagulation
      clinic for routine warfarin monitoring with an International Normalized Ratio
      (INR) value of 7.1 (therapeutic range, 2.0-3.0). His medical history included
      atrial flutter, hypertension, hyperlipidemia, diabetes mellitus, erectile
      dysfunction, obesity, and hypothyroidism. His medication regimen included
      warfarin, hydrochlorothiazide, lisinopril, levothyroxine, simvastatin, glyburide,
      metformin, vardenafil, aspirin, a multivitamin, and the herbal products Cataplex
      E2, Cataplex B, and Cyruta. The dosages of all medications and herbal products
      had been stable for the previous nine months, including warfarin (INR, 1.9-3.3).
      The patient began taking bee pollen granules (one teaspoon orally twice daily)
      for a perceived general health benefit one month before this clinic visit. He
      denied use of alcohol and tobacco, changes in dietary phytonadione intake, missed
      or extra doses of warfarin, any other medication changes, and acute illness and
      diarrhea. Warfarin was withheld, and the patient was seen at the anticoagulation
      clinic three days later with an INR of 3.7. Warfarin was held for a fourth day
      and then restarted with the weekly dose decreased by 11%. The patient continued
      to take bee pollen, and all INR values during the next seven months were within
      or near the therapeutic range. Use of the Drug Interaction Probability Scale
      indicated that there was a probable interaction between bee pollen and warfarin.
      CONCLUSION: Consumption of bee pollen led to increased INR values in a patient
      taking warfarin.

PMID- 21098376
TI  - Lipid and transaminase concentrations after formulary conversion of Niaspan to
      Slo-Niacin.
AB  - PURPOSE: Lipid and transaminase levels after conversion from immediate-release
      niacin to extended-release niacin were evaluated. METHODS: All patients who had
      their medications converted from Niaspan to Slo-Niacin between March 2008 and
      January 2009 were considered for evaluation. Subjects who took =2000 mg of
      Niaspan were automatically converted to Slo-Niacin in a 1:1 dosing ratio
      conversion. Mean aspartate transaminase (AST) and alanine transaminase (ALT)
      levels and lipid values (low-density-lipoprotein [LDL] cholesterol, high-density
      lipoprotein [HDL] cholesterol, and triglyceride levels) during Niaspan therapy
      were compared with the means of these values obtained after at least 90 days of
      Slo-Niacin therapy. Data were analyzed using the Wilcoxon rank-order test and
      frequency distributions. RESULTS: Of the 1172 patients who were identified as
      having had their Niaspan switched to Slo-Niacin after formulary conversion, 142
      met the inclusion criteria for this study. The majority of the patients had a
      decrease or no change in AST (72.5%) and ALT (69%) levels after at least 90 days
      of Slo-Niacin therapy. None of the patients had transaminase levels greater than
      three times the upper limit of normal during Slo-Niacin therapy. Differences in
      AST, ALT, triglyceride, and LDL cholesterol levels were not statistically
      significant between Niaspan and Slo-Niacin. On the other hand, patients' mean HDL
      cholesterol level was significantly greater with Slo-Niacin therapy than with
      Niaspan (42 mg/dL versus 40 mg/dL, respectively; p < 0.05). CONCLUSION: Formulary
      conversion from Niaspan to Slo-Niacin resulted in a small but significant
      increase in HDL cholesterol concentration and no significant change in ALT or AST
      level.

PMID- 21098377
TI  - Use of blogs by pharmacists.
AB  - PURPOSE: The characteristics of pharmacist blogs were examined. METHODS: Internet
      search engines, blog aggregators, and blog rolls were used to identify pharmacist
      blogs. Six categories were developed to evaluate blogs, including practice-based
      topics, identifying information, positive language, critical language,
      professionalism, and miscellaneous. The most recent five posts on each pharmacist
      blog were reviewed. Descriptive statistics were used to characterize the results.
      RESULTS: A total of 117 blogs were identified, 44 of which were designated as
      pharmacist blogs. No blogs contained patient-identifying information. Anonymity
      was maintained by 68.2% of bloggers. Bloggers practiced in community (43.1%) and
      noncommunity (43.1%) settings. Pharmacists most commonly used positive language
      to describe the profession (32%), other health care professionals (25%), and
      patients (25%). The highest rates of critical language were found in descriptions
      of patients (57%) and other health care professionals (44%). Almost half of
      pharmacist blogs contained explicit or unprofessional language. Overall,
      community practitioner blogs were substantially more likely than noncommunity
      practitioner blogs to use unprofessional and critical language. Twenty-five
      percent of pharmacist bloggers also maintained a microblog (e.g., Twitter)
      account. CONCLUSION: A search using Internet search engines, blog aggregators,
      and blog rolls identified 117 blogs, 44 of which met the study criteria for
      designation as pharmacist blogs. The majority of pharmacist blogs included some
      type of discussion of pharmacologic therapies. Pharmacists most commonly used
      positive language to describe the profession, other health care professionals,
      and patients. The highest rates of critical language were found in descriptions
      of patients and other health care professionals.

PMID- 21098378
TI  - Implementation of a telepharmacy service to provide round-the-clock medication
      order review by pharmacists.
AB  - Purpose The implementation of a telepharmacy service to provide round-the-clock
      medication order review by pharmacists is described. Summary Seven critical
      access hospitals (CAHs) worked collaboratively as part of a network of hospitals
      implementing the same electronic health record (EHR), computerized prescriber
      order-entry (CPOE) system, and pharmacy information system to serve as the health
      information technology (HIT) backbone supporting round-the-clock medication order
      review by pharmacists. Collaboration permitted standardization of workflow
      policies and procedures. Through the HIT backbone, both onsite and remote
      pharmacists were given access to the medication orders, the pharmacy information
      system, and other patient-specific clinical data in patients' EHRs. Orders are
      typically reviewed within 60 minutes of when they are entered into the system.
      The reviewing pharmacists have remote access to the EHRs in each CAH. After
      completing the clinical review, the pharmacist selects the appropriate medication
      to dispense from the CAH's formulary. If the medication order is not made using
      the CPOE system, the order is scanned into a document and sent via e-mail to
      remote pharmacists. The pharmacist enters the necessary information into the EHR
      and pharmacy information system. The medication order review process from this
      point forward is identical to that used for medications ordered via CPOE. The new
      medication order is then entered into the EHR, and the CAH nurse can proceed with
      the order. Conclusion The implementation of a telepharmacy model in a
      multihospital health system increased access to pharmacy services, allowing for
      round-the-clock medication order review by pharmacists.

PMID- 21098379
TI  - Challenges of medication management in hospitalized patients with Parkinson's
      disease.

PMID- 21098381
TI  - A section devoted to profiles of renown teachers and to the recognition and
      accomplishments of physiology teachers within the society.

PMID- 21098380
TI  - Investigation of adipose tissues in Zucker rats using in vivo and ex vivo
      magnetic resonance spectroscopy.
AB  - In vivo single-voxel magnetic resonance spectroscopy (MRS) at 4.7T and ex vivo
      high-resolution proton magnetic resonance spectroscopy (HR-NMR) at 500 MHz were
      used to study the composition of adipose tissues in Zucker obese and Zucker lean
      rats. Lipid composition was characterized by unsaturation and polyunsaturation
      indexes and mean chain lengths. In vitro experiments were conducted in known
      mixtures of triglycerides and oils in order to validate the method. To avoid
      inaccuracies due to partial peak overlapping in MRS, peak quantification was
      performed after fitting of spectral peaks by using the QUEST algorithm. The
      intensity of different spectral lines was also corrected for T2 relaxation.
      Albeit with different sensitivity and accuracy, both techniques revealed that
      white adipose tissue is characterized by lower unsaturation and polyunsaturation
      indexes in obese rats compared with controls. HR-NMR revealed similar differences
      in brown adipose tissue. The present findings confirm the hypothesis that obese
      and lean Zucker rats have different adipose tissue composition.

PMID- 21098382
TI  - Analogies in science and science teaching.
AB  - Analogies are often used in science, but students may not appreciate their
      significance, and so the analogies can be misunderstood or discounted. For this
      reason, educationalists often express concern about the use of analogies in
      teaching. Given the important place of analogies in the discourse of science, it
      is necessary that students are explicitly shown how they work, perhaps based on
      the structure-mapping theory we outline here. When using an analogy, the teacher
      should very clearly specify both its components and its limitations. Great care
      is required in developing an analogy to ensure that it is understood as intended
      and that misconceptions are minimized. This approach models the behavior of a
      scientist, which helps to develop student understanding of the practice of
      science.

PMID- 21098383
TI  - Student peer review decisions on submitted manuscripts are as stringent as
      faculty peer reviewers.
AB  - The International Journal of Exercise Science is the only student-centered peer
      reviewed journal in its field. Upon graduate student first author submissions,
      two student reviewers and one faculty reviewer are asked to review. On
      professionally submitted papers, two faculty peers are asked to assess the
      manuscript. The purpose of the present study was to determine whether graduate
      students returned similar decisions compared with faculty reviewers who evaluated
      the same manuscript. In addition, decisions of faculty peers reviewing graduate
      student- versus faculty-submitted manuscripts were compared. Mean comparisons
      between groups were evaluated using independent t-tests with significance at P <=
      0.05. Graduate students (2.21 +/- 0.69) and faculty peers (2.24 +/- 0.66)
      returned similar decisions on student-submitted manuscripts (P = 0.84). Faculty
      decisions on manuscripts submitted by a professional primary author (1.86 +/-
      0.77) were not different compared with faculty peers reviewing student
      manuscripts (P = 0.06). Statistics revealed that graduate students are just as
      stringent in the peer review process as established reviewers. Additionally,
      faculty reviewers evaluated manuscripts equally regardless of submission type.

PMID- 21098384
TI  - Diffusive insights: on the disagreement of Christian Bohr and August Krogh at the
      Centennial of the Seven Little Devils.
AB  - The year 2010 is the centennial of the publication of the "Seven Little Devils"
      in the predecessor of Acta Physiologica. In these seven papers, August and Marie
      Krogh sought to refute Christian Bohr's theory that oxygen diffusion from the
      lungs to the circulation is not entirely passive but rather facilitated by a
      specific cellular activity substitute to secretion. The subjects of the present
      reevaluation of this controversy are Christian Bohr, Professor and Doctor of
      Medicine (1855-1911), nominated three times for the Nobel Prize; August Krogh,
      Doctor of Philosophy (1874-1949), Christian Bohr's assistant and later Nobel
      Prize laureate (1920); and Marie Krogh, nee Jorgensen, Doctor of Medicine and
      wife of August Krogh (1874-1943). The controversy concerned is the transport of
      oxygen from the lungs into the bloodstream: are passive transport and diffusion
      capacity together sufficient to secure the oxygen supply in all circumstances or
      is there an additional specific ("energy consuming" or "active") mechanism
      responsible for the transport of oxygen from the alveoli into the bloodstream?
      The present discussion purports to show that the contestants' views were closer
      than the parties themselves and posterity recognized. Posterity has judged the
      dispute unilaterally from the Nobel laureate's point of view, but it is evident
      that August Krogh's Nobel Prize was awarded for the discovery of a cellular
      activity (Christian Bohr's expression), represented by Krogh's discovery of
      capillary recruitment. Christian Bohr appears to have been correct in the
      narrower sense that the diffusion capacity at rest is not great enough to explain
      the transport during work; a special mechanism intervenes and optimizes the
      conditions under which diffusion acts. August Krogh, of course, was right in the
      wider sense that the transport mechanism itself is always entirely passive.

PMID- 21098385
TI  - Explorations in statistics: correlation.
AB  - Learning about statistics is a lot like learning about science: the learning is
      more meaningful if you can actively explore. This sixth installment of
      Explorations in Statistics explores correlation, a familiar technique that
      estimates the magnitude of a straight-line relationship between two variables.
      Correlation is meaningful only when the two variables are true random variables:
      for example, if we restrict in some way the variability of one variable, then the
      magnitude of the correlation will decrease. Correlation cannot help us decide if
      changes in one variable result in changes in the second variable, if changes in
      the second variable result in changes in the first variable, or if changes in a
      third variable result in concurrent changes in the first two variables.
      Correlation can help provide us with evidence that study of the nature of the
      relationship between x and y may be warranted in an actual experiment in which
      one of them is controlled.

PMID- 21098386
TI  - Can learning style predict student satisfaction with different instruction
      methods and academic achievement in medical education?
AB  - The curriculum of our medical school has a hybrid structure including both
      traditional training (lectures) and problem-based learning (PBL) applications.
      The purpose of this study was to determine the learning styles of our medical
      students and investigate the relation of learning styles with each of
      satisfaction with different instruction methods and academic achievement in them.
      This study was carried out with the participation of 170 first-year medical
      students (the participation rate was 91.4%). The researchers prepared
      sociodemographic and satisfaction questionnaires to determine the characteristics
      of the participants and their satisfaction levels with traditional training and
      PBL. The Kolb learning styles inventory was used to explore the learning styles
      of the study group. The participants completed all forms at the end of the first
      year of medical education. Indicators of academic achievement were scores of five
      theoretical block exams and five PBL exams performed throughout the academic year
      of 2008-2009. The majority of the participants took part in the "diverging" (n =
      84, 47.7%) and "assimilating" (n = 73, 41.5%) groups. Numbers of students in the
      "converging" and "accommodating" groups were 11 (6.3%) and 8 (4.5%),
      respectively. In all learning style groups, PBL satisfaction scores were
      significantly higher than those of traditional training. Exam scores for "PBL and
      traditional training" did not differ among the four learning styles. In logistic
      regression analysis, learning style (assimilating) predicted student satisfaction
      with traditional training and success in theoretical block exams. Nothing
      predicted PBL satisfaction and success. This is the first study conducted among
      medical students evaluating the relation of learning style with student
      satisfaction and academic achievement. More research with larger groups is needed
      to generalize our results. Some learning styles may relate to satisfaction with
      and achievement in some instruction methods.

PMID- 21098387
TI  - A comparison between learning style preferences and sex, status, and course
      performance.
AB  - Students have learning style preferences that are often classified according to
      their visual (V), aural (A), read-write (R), and/or kinesthetic (K) sensory
      modality preferences (SMP). The purposes of this investigation were to compare
      student perceived and assessed SMPs and examine the associations between those
      SMPs and status (i.e., undergraduates vs. graduates), sex, and course
      performance. Students from the fall 2009 APK 3110 and APK 6116 Exercise
      Physiology courses were asked to indicate their perceived SMPs and complete the
      standard VARK SMP assessment. There were 64 student respondents: 50
      undergraduates and 14 graduates (40 women and 24 men). According to the perceived
      SMP results, the largest number of respondents chose V (36%), followed by R
      (28%), K (19%), and A (17%). In terms of assessed SMPs, the largest number of
      respondents were classified as VARK (37%), followed by R (14%), AK (11%), K (8%),
      VK (6%), ARK (6%), A (5%), VAK (3%), RK (3%), V (2%), AR (2%), and VRK (2%).
      Nearly two-thirds of the respondents correctly matched their perceived and
      dominant assessed SMP. There was no statistical association between SMP and
      status. There was a very nearly significant relationship between sex and both
      perceived (chi(2) = 7.18, P = 0.06) and assessed (chi(2) = 17.36, P = 0.09) SMP.
      Finally, there was a significant relationship between perceived SMP and course
      scores (P = 0.01 by ANOVA). Post hoc tests revealed that the K group scored
      significantly lower than the other three modality groups.

PMID- 21098388
TI  - Teaching medical students basic neurotransmitter pharmacology using primary
      research resources.
AB  - Teaching pharmacology to medical students has long been seen as a challenge, and
      one to which a number of innovative approaches have been taken. In this article,
      we describe and evaluate the use of primary research articles in teaching second
      year medical students both in terms of the information learned and the use of the
      papers themselves. We designed a seminar where small groups of students worked on
      different neurotransmitters before contributing information to a plenary session.
      Student feedback suggested that when the information was largely novel, students
      learned considerably more. Crucially, this improvement in knowledge was seen even
      when they had not directly studied a particular transmitter in their work groups,
      suggesting a shared learning experience. Moreover, the majority of students
      reported that using primary research papers was easy and useful, with over half
      stating that they would use them in future study.

PMID- 21098389
TI  - Are online student evaluations of faculty influenced by the timing of
      evaluations?
AB  - Student evaluations of faculty are important components of the medical curriculum
      and faculty development. To improve the effectiveness and timeliness of student
      evaluations of faculty in the physiology course, we investigated whether
      evaluations submitted during the course differed from those submitted after
      completion of the course. A secure web-based system was developed to collect
      student evaluations that included numerical rankings (1-5) of faculty performance
      and a section for comments. The grades that students received in the course were
      added to the data, which were sorted according to the time of submission of the
      evaluations and analyzed by Pearson's correlation and Student's t-test. Only 26%
      of students elected to submit evaluations before completion of the course, and
      the average faculty ratings of these evaluations were highly correlated [r(14) =
      0.91] with the evaluations submitted after completion of the course. Faculty
      evaluations were also significantly correlated with the previous year [r(14) =
      0.88]. Concurrent evaluators provided more comments that were statistically
      longer and subjectively scored as more "substantive." Students who submitted
      their evaluations during the course and who included comments had significantly
      higher final grades in the course. In conclusion, the numeric ratings that
      faculty received were not influenced by the timing of student evaluations.
      However, students who submitted early evaluations tended to be more engaged as
      evidenced by their more substantive comments and their better performance on
      exams. The consistency of faculty evaluations from year to year and concurrent
      versus at the end of the course suggest that faculty tend not to make significant
      adjustments to student evaluations.

PMID- 21098390
TI  - A demonstration of sympathetic cotransmission.
AB  - Currently, most undergraduate textbooks that cover the autonomic nervous system
      retain the concept that autonomic nerves release either acetylcholine or
      norepinephrine. However, in recent years, a large volume of research has
      superseded this concept with one in which autonomic nerves normally release at
      least one cotransmitter along with a dominant transmitter that may or may not be
      acetylcholine or norepinephrine. Cotransmission involving the simultaneous
      release of norepinephrine, ATP, and neuropeptide Y can easily be demonstrated in
      an isometric ring preparation of the rat tail artery, which is described here.
      The experiment clearly demonstrates the principle of cotransmission but allows
      more advanced concepts in autonomic cotransmission to be addressed.

PMID- 21098391
TI  - Not only students can express alcohol dehydrogenase: goldfish can too!
AB  - This article describes a novel approach to study the metabolic regulation of the
      respiratory system in vertebrates that suits physiology lessons for undergraduate
      students. It consists of an experimental demonstration of the goldfish's
      (Carassius auratus) adaptations to anoxia. The goldfish is one of the few
      vertebrates showing strong enzymatic plasticity for the expression of alcohol
      dehydrogenase (ADH), which allows it to survive long periods of severe anoxia.
      Therefore, we propose two simple laboratory exercises in which students are first
      asked to characterize the distribution of ADH isozymes in the goldfish by
      performing cellulose acetate electrophoresis. The second part of this laboratory
      lesson is the determination of liver glycogen. To further student comprehension,
      an interspecies comparative component is integrated, in which the same subjects
      are studied in an anoxia-sensitive species, the brook charr (Salvelinus
      fontinalis). ADH in goldfish is restricted to skeletal muscles, where it
      catalyzes alcoholic fermentation, permitting ethanol excretion through the gills
      and therefore preventing lactate acidosis caused by sustained glycolysis during
      anoxia. Electrophoresis also reveals the occurrence of a liver isozyme in the
      brook charr, which ADH catalyzes in the opposite pathway, allowing the usual
      ethanol degradation. As for the liver glycogen assay, it shows largely superior
      content in the goldfish liver compared with the brook charr, providing goldfish
      with a sustained energy supply during anoxia. The results of this laboratory
      exercise clearly demonstrate several physiological strategies developed by
      goldfish to cope with such a crucial environmental challenge as oxygen depletion.

PMID- 21098392
TI  - How does a hopping kangaroo breathe?
AB  - We developed a model to demonstrate how a hopping kangaroo breathes.
      Interestingly, a kangaroo uses less energy to breathe while hopping than while
      standing still. This occurs, in part, because rather than using muscle power to
      move air into and out of the lungs, air is pulled into (inspiration) and pushed
      out of (expiration) the lungs as the abdominal organs "flop" within the
      kangaroo's body. Specifically, as the kangaroo hops upward, the abdominal organs
      lag behind, and the insertion of the diaphragm is pulled toward its origin,
      flattening the dome and increasing the vertical dimension of the thoracic cavity
      (the thoracic cavity and lungs enlarge). Increasing the volume of the thoracic
      cavity reduces alveolar pressure below atmospheric pressure (barometric
      pressure), and air moves into the alveoli by bulk flow. In contrast, the impact
      of the organs against the diaphragm at each landing causes expiration.
      Specifically, upon landing, the abdominal organs flop into the diaphragm, causing
      it to return to its dome shape and decreasing the vertical dimension of the
      thoracic cavity. This compresses the alveolar gas volume and elevates alveolar
      pressure above barometric pressure, so air is expelled. To demonstrate this
      phenomenon, the plunger of a syringe model of the respiratory system was inserted
      through a compression spring. Holding the syringe and pressing the plunger firmly
      against a hard surface expels air from the lungs (the balloon within the syringe
      deflates) and compresses the spring. This models the kangaroo landing after a hop
      forward. Subsequently, the compression spring provides the energy for the
      "kangaroo" to "hop" forward upon the release of the syringe, and air enters the
      lungs (the balloon within the syringe inflates). The model accurately reflects
      how a hopping kangaroo breathes. A model was chosen to demonstrate this
      phenomenon because models engage and inspire students as well as significantly
      enhance student understanding.

PMID- 21098393
TI  - Teaching acid/base physiology in the laboratory.
AB  - Acid/base homeostasis is one of the most difficult subdisciplines of physiology
      for medical students to master. A different approach, where theory and practice
      are linked, might help students develop a deeper understanding of acid/base
      homeostasis. We therefore set out to develop a laboratory exercise in acid/base
      physiology that would provide students with unambiguous and reproducible data
      that clearly would illustrate the theory in practice. The laboratory exercise was
      developed to include both metabolic acidosis and respiratory alkalosis. Data were
      collected from 56 groups of medical students that had participated in this
      laboratory exercise. The acquired data showed very consistent and solid findings
      after the development of both metabolic acidosis and respiratory alkalosis. All
      results were consistent with the appropriate diagnosis of the acid/base disorder.
      Not one single group failed to obtain data that were compatible with the
      diagnosis; it was only the degree of acidosis/alkalosis and compensation that
      varied.

PMID- 21098394
TI  - A qualitative analogy for respiratory mechanics.

PMID- 21098395
TI  - Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify
      NK-derived IFN{gamma}: role of CD18, ICAM-1, and ICAM-3.
AB  - The role of neutrophils as key players in the regulation of innate and adaptive
      immune responses is increasingly being recognized. We report that human
      neutrophils establish a network with both natural killer (NK) cells and 6-sulfo
      LacNAc(+) dendritic cells (slanDCs), which ultimately serves to up-regulate NK
      derived interferongamma (IFNgamma). This network involves direct reciprocal
      interactions and positive amplification loops mediated by cell-derived cytokines.
      Accordingly, we show that after lipopolysaccharide + interleukin-2 (IL-2) or IL
      15/IL-18 stimulation, neutrophils directly interact with and potentiate the
      activity of both slanDCs and NK cells. On the one hand, neutrophils augment the
      release of IL-12p70 by slanDCs via a CD18/ intercellular adhesion molecule-1
      (ICAM-1) interaction that stimulates activated NK cells to produce IFNgamma.
      IFNgamma further potentiates the interaction between neutrophils and slanDCs and
      the release of slanDC-derived IL-12p70, thus creating a positive feedback loop.
      On the other hand, neutrophils directly co-stimulate NK cells via CD18/ICAM-3,
      leading to the production of IFNgamma. Colocalization of neutrophils, NK cells,
      and slanDCs, as well as of IL-12p70 and IFNgamma, in inflamed tissues of Crohn
      disease and psoriasis provides strong evidence for a novel cellular and cytokine
      cooperation within the innate immune system in which neutrophils act as
      amplifiers of NK cell/slanDC-mediated responses.

PMID- 21098396
TI  - Immunoglobulin light chains activate nuclear factor-kappaB in renal epithelial
      cells through a Src-dependent mechanism.
AB  - One of the major attendant complications of multiple myeloma is renal injury,
      which contributes significantly to morbidity and mortality in this disease.
      Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved,
      and tubulointerstitial renal injury and fibrosis are prominent histologic
      features observed in myeloma. The present study examined the role of monoclonal
      FLCs in altering the nuclear factor kappa light chain enhancer of activated B
      cells (NF-kappaB) activity of renal epithelial cells. Human proximal tubule
      epithelial cells exposed to 3 different human monoclonal FLCs demonstrated Src
      kinase-dependent activation of the NF-kappaB pathway, which increased production
      of monocyte chemoattractant protein-1 (MCP-1). Tyrosine phosphorylation of
      inhibitor of kappaB kinases (IKKs) IKKalpha and IKKbeta and a concomitant
      increase in inhibitor of kappaB (IkappaB) kinase activity in cell lysates were
      observed. Time-dependent, Src kinase-dependent increases in serine and tyrosine
      phosphorylation of IkappaBalpha and NF-kappaB activity were also demonstrated.
      Proteasome inhibition partially blocked FLC-induced MCP-1 production. These
      findings fit into a paradigm characterized by FLC-induced redox-signaling events
      that activated the canonical and atypical (IKK-independent) NF-kappaB pathways to
      promote a proinflammatory, profibrotic renal environment.

PMID- 21098397
TI  - Allogeneic hematopoietic cell transplantation for adults with acute myeloid
      leukemia: myths, controversies, and unknowns.
AB  - Progress in the last decade has improved the understanding of leukemia biology.
      Molecular markers in combinations with cytogenetics have improved the risk
      stratification of acute myeloid leukemia (AML) and informed decision-making. In
      parallel, several important advances in the transplant field, such as better
      supportive care, improved transplant technology, increased availability of
      alternative donors, and reduced-intensity conditioning have improved the safety
      as well as access of allogeneic hematopoietic cell transplantation (HCT) for a
      larger number of patients. In this review, the positioning of HCT in the
      management of patients with AML is evaluated in view of changing risk/benefit
      ratios associated with both conventional treatments and transplantation, and some
      of the controversies are addressed in light of emerging data. Increasing data
      demonstrate outcomes of alternative donor transplantation approaching HLA
      identical sibling donors in high-risk AML supporting the inclusion of alternative
      donors in trials of prospective studies evaluating post remission strategies for
      high-risk AML. The use of reduced-intensity conditioning has expanded the
      eligibility of HCT to older patients with AML, and outcome data are encouraging.
      Continued study of HCT versus alternative therapies is required to optimize
      patients' outcomes in AML.

PMID- 21098398
TI  - Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the
      pathogenesis of mouse and human CLL.
AB  - Inhibitor of DNA binding protein 4 (ID4) is a member of the dominant-negative
      basic helix-loop-helix transcription factor family that lacks DNA binding
      activity and has tumor suppressor function. ID4 promoter methylation has been
      reported in acute myeloid leukemia and chronic lymphocytic leukemia (CLL),
      although the expression, function, and clinical relevance of this gene have not
      been characterized in either disease. We demonstrate that the promoter of ID4 is
      consistently methylated to various degrees in CLL cells, and increased promoter
      methylation in a univariable analysis correlates with shortened patient survival.
      However, ID4 mRNA and protein expression is uniformly silenced in CLL cells
      irrespective of the degree of promoter methylation. The crossing of ID4(+/-) mice
      with EMU-TCL1 mice triggers a more aggressive murine CLL as measured by
      lymphocyte count and inferior survival. Hemizygous loss of ID4 in nontransformed
      TCL1-positive B cells enhances cell proliferation triggered by CpG
      oligonucleotides and decreases sensitivity to dexamethasone-mediated apoptosis.
      Collectively, this study confirms the importance of the silencing of ID4 in
      murine and human CLL pathogenesis.

PMID- 21098401
TI  - Pearls & Oy-sters: optic tract syndrome.

PMID- 21098399
TI  - Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase
      after imatinib resistance or intolerance: 24-month follow-up results.
AB  - Nilotinib is a potent selective inhibitor of the BCR-ABL tyrosine kinase approved
      for use in patients with newly diagnosed chronic myeloid leukemia in chronic
      phase (CML-CP), and in CML-CP and CML-accelerated phase after imatinib failure.
      Nilotinib (400 mg twice daily) was approved on the basis of the initial results
      of this phase 2 open-label study. The primary study endpoint was the proportion
      of patients achieving major cytogenetic response (CyR). All patients were
      followed for >= 24 months or discontinued early. Of 321 patients, 124 (39%)
      continue on nilotinib treatment. Overall, 59% of patients achieved major CyR;
      this was complete CyR (CCyR) in 44%. Of patients achieving CCyR, 56% achieved
      major molecular response. CyRs were durable, with 84% of patients who achieved
      CCyR maintaining response at 24 months. The overall survival at 24 months was
      87%. Adverse events were mostly mild to moderate, generally transient, and easily
      managed. This study indicates that nilotinib is effective, with a manageable
      safety profile, and can provide favorable long-term benefits for patients with
      CML-CP after imatinib failure.

PMID- 21098402
TI  - Teaching NeuroImages: a giant developmental venous anomaly in the absence of a
      superficial venous drainage system.

PMID- 21098403
TI  - Imaging correlates of pathology in corticobasal syndrome.
AB  - BACKGROUND: Corticobasal syndrome (CBS) can be associated with different
      underlying pathologies that are difficult to predict based on clinical
      presentation. The aim of this study was to determine whether patterns of atrophy
      on imaging could be useful to help predict underlying pathology in CBS. METHODS:
      This was a case-control study of 24 patients with CBS who had undergone MRI
      during life and came to autopsy. Pathologic diagnoses included frontotemporal
      lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer
      disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and
      progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas
      based parcellation were used to assess atrophy across the CBS groups and compared
      to 24 age- and gender-matched controls. RESULTS: All CBS pathologic groups showed
      gray matter loss in premotor cortices, supplemental motor area, and insula on
      imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss,
      with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in
      CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the
      other groups, whereas CBS-AD showed significantly greater loss in parietal lobe
      than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP,
      although more severe in CBS-CBD. CONCLUSIONS: Imaging patterns of atrophy in CBS
      vary according to pathologic diagnosis. Widespread atrophy points toward a
      pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD
      TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy
      predominantly involving the premotor and supplemental motor area suggests CBD or
      PSP pathology.

PMID- 21098404
TI  - Brain N-acetylaspartate levels correlate with motor function in metachromatic
      leukodystrophy.
AB  - BACKGROUND: Late infantile metachromatic leukodystrophy (MLD) is an autosomal
      recessive lysosomal storage disorder that causes severe demyelination of the
      nervous system. The neuronal metabolite N-acetylaspartate (NAA) serves as a
      source of acetyl groups for myelin lipid synthesis in oligodendrocytes and is
      known as a marker for neuronal and axonal loss. NAA and other metabolite levels
      measured by proton magnetic resonance spectroscopy (MRS) correlate with
      performance of the brain in normal children. There is a need for sensitive
      measures of disease progression in patients with MLD to enable development of
      future treatments. METHODS: A cross-section of 13 children with late infantile
      MLD were examined by proton MRS. Signals from NAA, total choline, and total
      creatine in the deep white matter were measured and correlated with the results
      of cognitive and motor function tests. RESULTS: The NAA signal decreased as the
      disease process advanced. Motor function, measured by the Gross Motor Function
      Measure-88, varied from 13 (only head movement in the supine position) to 180
      (able to walk) across the study cohort, demonstrating a wide range in functional
      status. Similarly, varied decreases were observed in cognitive function. We
      report strong positive correlations between standardized measures of motor and
      cognitive function and NAA levels in the deep white matter. CONCLUSIONS: We
      suggest that NAA levels could serve as a sensitive biomarker in children with
      MLD. Proton MRS may provide a valuable tool for measuring the effects of
      treatment interventions in this disorder.

PMID- 21098405
TI  - Afferent baroreflex failure in familial dysautonomia.
AB  - BACKGROUND: Familial dysautonomia (FD) is due to a genetic deficiency of the
      protein IKAP, which affects development of peripheral neurons. Patients with FD
      display complex abnormalities of the baroreflex of unknown cause. METHODS: To
      test the hypothesis that the autonomic phenotype of FD is due to selective
      impairment of afferent baroreceptor input, we examined the autonomic and
      neuroendocrine responses triggered by stimuli that either engage (postural
      changes) or bypass (cognitive/emotional) afferent baroreflex pathways in 50
      patients with FD and compared them to those of normal subjects and to those of
      patients with pure autonomic failure (PAF), a disorder with selective impairment
      of efferent autonomic neurons. RESULTS: During upright tilt, in patients with FD
      and in patients with PAF blood pressure fell markedly but the heart rate
      increased in PAF and decreased in FD. Plasma norepinephrine levels failed to
      increase in both groups. Vasopressin levels increased appropriately in patients
      with PAF but failed to increase in patients with FD. Head-down tilt increased
      blood pressure in both groups but increased heart rate only in patients with FD.
      Mental stress evoked a marked increase in blood pressure and heart rate in
      patients with FD but little change in those with PAF. CONCLUSION: The failure to
      modulate sympathetic activity and to release vasopressin by baroreflex-mediated
      stimuli together with marked sympathetic activation during cognitive tasks
      indicate selective failure of baroreceptor afference. These findings indicate
      that IKAP is critical for the development of afferent baroreflex pathways and has
      therapeutic implications in the management of these patients.

PMID- 21098406
TI  - Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: a
      randomized trial.
AB  - OBJECTIVE: Dysphagia is the main cause of aspiration pneumonia and death in
      Parkinson disease (PD) with no established restorative behavioral treatment to
      date. Reduced swallow safety may be related to decreased elevation and excursion
      of the hyolaryngeal complex. Increased submental muscle force generation has been
      associated with expiratory muscle strength training (EMST) and subsequent
      increases in hyolaryngeal complex movement provide a strong rationale for its use
      as a dysphagia treatment. The current study's objective was to test the treatment
      outcome of a 4-week device-driven EMST program on swallow safety and define the
      physiologic mechanisms through measures of swallow timing and hyoid displacement.
      METHODS: This was a randomized, blinded, sham-controlled EMST trial performed at
      an academic center. Sixty participants with PD completed EMST, 4 weeks, 5 days
      per week, for 20 minutes per day, using a calibrated or sham, handheld device.
      Measures of swallow function including judgments of swallow safety (penetration
      aspiration [PA] scale scores), swallow timing, and hyoid movement were made from
      videofluoroscopic images. RESULTS: No pretreatment group differences existed. The
      active treatment (EMST) group demonstrated improved swallow safety compared to
      the sham group as evidenced by improved PA scores. The EMST group demonstrated
      improvement of hyolaryngeal function during swallowing, findings not evident for
      the sham group. CONCLUSIONS: EMST may be a restorative treatment for dysphagia in
      those with PD. The mechanism may be explained by improved hyolaryngeal complex
      movement. CLASSIFICATION OF EVIDENCE: This intervention study provides Class I
      evidence that swallow safety as defined by PA score improved post EMST.

PMID- 21098408
TI  - Head position during resting modifies spontaneous daytime decrease of downbeat
      nystagmus.
AB  - BACKGROUND: The intensity of downbeat nystagmus (DBN) decreases during the
      daytime when the head is in upright position. OBJECTIVE: This prospective study
      investigated whether resting in different head positions (upright, supine, prone)
      modulates the intensity of DBN after resting. METHODS: Eye movements of 9
      patients with DBN due to cerebellar (n = 2) or unknown etiology (n = 7) were
      recorded with video-oculography. Mean slow-phase velocities (SPV) of DBN were
      determined in the upright position before resting at 9 am and then after 2 hours
      (11 am) and after 4 hours (1 pm) of resting. Whole-body positions during resting
      were upright, supine, or prone. The effects of all 3 resting positions were
      assessed on 3 separate days in each patient. RESULTS: Before resting (9 am), the
      average SPV ranged from 3.05  degrees /s to 3.6  degrees /s on the separate days
      of measurement. After resting in an upright position, the average SPV at 11 am
      and 1 pm was 0.65  degrees /sec, which was less (p < 0.05) than after resting in
      supine (2.1  degrees /sec) or prone (2.22  degrees /sec) positions. CONCLUSION:
      DBN measured during the daytime in an upright position becomes minimal after the
      patient has rested upright. The spontaneous decrease of DBN is less pronounced
      when patients lie down to rest. This indicates a modulation by otolithic input.
      We recommend that patients with DBN rest in an upright position during the
      daytime. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that
      for patients with DBN 2 hours of rest in the upright position decreases nystagmus
      more than 2 hours of rest in the supine or prone positions (relative improvement
      79% upright, 33% supine, and 38% prone: p < 0.05).

PMID- 21098407
TI  - Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic
      structures.
AB  - BACKGROUND: Depression associated with Parkinson disease (PD) has a different
      symptom profile to endogenous depression. The etiology of depression in PD
      remains uncertain though abnormal serotonergic neurotransmission could play a
      role. OBJECTIVE: To assess with PET serotonergic function via in vivo serotonin
      transporter (5-HTT) availability in antidepressant-naive patients with PD.
      METHODS: Thirty-four patients with PD and 10 healthy matched control subjects had
      a clinical battery of tests including the patient-report Beck Depression
      Inventory-II (BDI-II), the clinician-report Hamilton Rating Scale for Depression
      (HRSD), and the structured clinical interview for DSM-IV Axis I Disorders (SCID
      I). They underwent 11C-DASB PET, a selective in vivo marker of 5-HTT binding in
      humans. RESULTS: BDI-II scores correlated with HRSD scores. Ten of 34 patients
      with PD (29.4%) had BDI-II and HRSD scores above the discriminative cutoff for PD
      depression though only half of these patients could be classed on SCID-I criteria
      as having an anxiety/mood disorder. Patients with PD with the highest scores for
      depression symptoms showed significantly raised 11C-DASB binding in amygdala,
      hypothalamus, caudal raphe nuclei, and posterior cingulate cortex compared to low
      score cases, while 11C-DASB binding values in other regions were similarly
      decreased in depressed and nondepressed patients with PD compared to healthy
      controls. CONCLUSION: Depressive symptoms in antidepressant-naive patients with
      PD correlate with relatively higher 5-HTT binding in raphe nuclei and limbic
      structures possibly reflecting lower extracellular serotonin levels. Our data are
      compatible with a key role of abnormal serotonergic neurotransmission
      contributing to the pathophysiology of PD depression and justify the use of
      agents acting on 5-HTT.

PMID- 21098409
TI  - Brainstem lesions in clinically isolated syndromes.
AB  - BACKGROUND: Number of baseline lesions has been shown to predict future attacks
      and disability in clinically isolated syndromes (CIS). OBJECTIVE: To investigate
      the role of baseline infratentorial lesions in long-term prognosis. METHODS:
      Subjects were included in a prospective cohort of patients with CIS. Patients
      underwent brain MRI within 3 months after CIS onset. Number and location of
      lesions at baseline were prospectively studied. Retrospective scan analysis was
      conducted to specifically look at number and location of infratentorial lesions.
      We analyzed the time to a second attack and to reach EDSS 3.0. RESULTS: We
      included 246 patients with CIS followed for a median of 7.7 years. Patients with
      infratentorial lesions had both a higher risk of conversion (71.4% vs 29.6%;
      hazard ratio [HR] 3.3; 95% confidence interval [CI] 2.2-4.8; p < 0.001) and of
      developing disability (32.5% vs 12.4%; HR 2.4; 95% CI 1.3-4.3; p = 0.003).
      Presence of at least one cerebellar lesion was associated with an increased risk
      of conversion (HR 2.4; 95% CI 1.3-4.5; p = 0.007). Presence of at least one
      brainstem lesion increased both the risk of conversion (HR 2.9; 95% CI 1.7-5.0; p
      < 0.001) and disability (HR 2.5; 95% CI 1.1-5.4; p = 0.026). Broken down into
      number of lesions, the presence of infratentorial lesions increased both the risk
      of conversion (83% vs 61%) (HR 22.3; 95% CI 9.7-51.1; p < 0.001) and of reaching
      EDSS 3.0 (40% vs 19%) (HR 3.2; 95% CI 1.3-7.4; p = 0.008) only in patients with 9
      or more lesions. CONCLUSIONS: Presence of infratentorial lesions increases the
      risk for disability. Brainstem rather than cerebellar lesions may be responsible
      for poor prognosis.

PMID- 21098411
TI  - A rare complication of azotemic hyperparathyroidism: ischemic calcific myopathy.

PMID- 21098410
TI  - Licorice-associated reversible cerebral vasoconstriction with PRES.

PMID- 21098412
TI  - The delayed-start study in Parkinson disease: can't satisfy everyone: Rasagiline,
      Parkinson neuroprotection, and delayed-start trials: still no satisfaction?

PMID- 21098414
TI  - Treatment of atrial fibrillation in 2010 and beyond.

PMID- 21098415
TI  - A new agent for atrial fibrillation: electrophysiological properties of
      dronedarone.
AB  - Although originally synthesized as an antianginal compound, amiodarone has
      emerged as an effective antiarrhythmic for both supraventricular and ventricular
      arrhythmias. Over the decades, the properties, the effectiveness, the merits as
      well as the shortcomings of the compound have been well established. The major
      limitations of this agent are mainly due to the systemic side effects seen with
      prolonged therapy. Many of the toxic effects observed are primarily caused by the
      high iodine content present in the amiodarone molecule. Dronedarone, the first
      noniodinated amiodarone congener, has been developed largely to obtain the
      antiarrhythmic efficacy in the control of atrial fibrillation without the known
      adverse side effects of dronedarone. In this part of the supplement, the focus is
      the electrophysiological effects of dronedarone with the characterization in
      normal cardiac cells, in animal models of disease, as well as in human studies.

PMID- 21098416
TI  - A review of the appropriate and inappropriate use of dronedarone: lessons learned
      from controlled studies and regulatory submission.
AB  - Dronedarone is a multichannel blocker with electrophysiologic effects similar to
      amiodarone. Dronedarone has been documented to prevent atrial fibrillation
      recurrences and also has efficacy in slowing the ventricular response during
      episodes of atrial fibrillation. However, in the ANDROMEDA trial, dronedarone was
      associated with increased mortality when tested in New York Heart Association
      (NYHA) III/IV patients with left ventricular ejection fractions of less than 35%,
      who also had a recent hospitalization for decompensated heart failure. When such
      high-risk patients with heart failure were excluded in the ATHENA trial,
      dronedarone treatment resulted in a statistical reduction in the composite
      primary end point of all-cause mortality or cardiovascular hospitalization. In
      ATHENA, dronedarone reduced cardiovascular hospitalizations even though in the
      DIONY-SOS trial dronedarone had less effect than amiodarone on suppressing atrial
      fibrillation recurrences. The most appropriate patients for treatment with
      dronedarone would be patients with a recent history of paroxysmal or persistent
      atrial fibrillation/atrial flutter (AF/AFL) that have associated risk factors per
      the inclusion criteria of ATHENA. Inappropriate patients would be those with
      class IV heart failure or recently hospitalized for heart failure within the last
      month from an acute decompensation, the main inclusion criteria in ANDROMEDA.
      Dronedarone is a novel, multichannel blocking antiarrhythmic agent that may have
      some pleiotropic effects in addition to its ability to suppress and maintain
      sinus rhythm and control the rate during AF/AFL recurrences.

PMID- 21098417
TI  - Augmenting maintenance of sinus rhythm in the control of atrial fibrillation by
      antiarrhythmic drug combinations.
AB  - In recent years, a major development in the treatment of atrial fibrillation (AF)
      is the use of catheter ablation, and a significant number of patients may benefit
      from this mode of therapy. On a global scale, it may not be feasible to deal with
      most patients solely on the basis of ablation. Therefore, it is likely that much
      of the therapy for AF will continue to rely on antiarrhythmic agents for
      maintaining sinus rhythm. For many years, amiodarone and sotalol have been the
      dominant antiarrhythmic agents, with amiodarone being the most effective
      antiarrhythmic in suppressing AF; however, amiodarone use is limited due to
      concerns of end-organ toxicity. Upstream therapies, such as statins, fish oil,
      angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers
      may also provide additive efficacy to these and other membrane-active
      antiarrhythmics. In recent years, a number of new agents are being developed and
      the first successful congener of amiodarone, dronedarone, has been shown to be
      effective in controlling AF and reducing cardiovascular hospitalization. This
      paper explores the possibility of augmenting the extent of controlling AF by
      combining multiple potent antiarrhythmic agents old and new.

PMID- 21098418
TI  - Review article: current status of myocardial regeneration: new cell sources and
      new strategies.
AB  - Clinical trials of stem cell therapy in cardiology are based upon a reasonably
      solid foundation in animal laboratory research. The most widely used cell source
      in clinical trials has been the patient's own reconstituted bone marrow cell
      (BMC) aspirate. Cell sources in human bone marrow include hematopoietic stem
      cells, mesenchymal progenitor cells, and other cell types with many desirable
      characteristics. In vitro, they can be induced to become typical sarcomeres with
      centrally positioned nuclei and abundant mitochondria and to express atrial
      natriuretic peptide (ANP), brain natriuretic peptide (BNP), and contractile
      proteins including myosin heavy chain, myosin light chain, and alpha actin.
      Intracoronary BMC infusion significantly decreases infarct size, increases
      myocardial perfusion, and improves regional and global cardiac function. Meta
      analyses of clinical trials of intracoronary autologous BMC infusion following
      acute myocardial infarction (MI) report that the mean absolute increase in
      ejection fraction (EF) is approximately 3% to 4%. This modest improvement in
      function appears to persist for 1 year. Some trials have shown that clinical
      events are reduced at 12 months, but others have reported no long-term clinical
      benefit, and the only 5-year follow-up suggests persistent benefit with decreased
      mortality, but also little evidence of significant myocardial regeneration in
      humans. These results have led to efforts to identify better cell sources and to
      create more conducive myocardial environment for cell proliferation. Among the
      cell types are skeletal myoblasts, cardiac stem cells, and induced pluripotent
      stem cells. Environmental modifiers are designed to increase cell survival,
      persistence, and proliferation.

PMID- 21098420
TI  - Mycotic aneurysm of the thoracic aorta caused by extended-spectrum beta-lactamase
      producing Escherichia coli.
AB  - We report a case of successful treatment of a mycotic aneurysm of the thoracic
      aorta. A 65-year-old man with a dissecting aneurysm presented with urinary tract
      infection. He had a history of severe liver cirrhosis. Two weeks after admission,
      he had a high-grade fever and enhanced computed tomography (CT) demonstrated
      acute expansion of the distal aortic arch aneurysm. Because of the acute aneurysm
      expansion and elevated inflammatory response, we suspected a mycotic aortic
      aneurysm with possible impending rupture. Since conventional open chest surgery
      was considered to carry a high operative risk, the patient was managed with a
      combination of emergency endovascular treatment and antibiotic chemotherapy.
      Extended-spectrum beta-lactamase-producing Escherichia coli were identified from
      blood culture before treatment. After strict antibiotic therapy, the
      postoperative course was uneventful and the patient remained well 12 months
      later.

PMID- 21098421
TI  - Delayed subtotal coronary obstruction after transapical aortic valve
      implantation.
AB  - We report on an obstruction of the left main coronary artery which occurred after
      completion of an uneventful transapical aortic valve implantation (TAVI)
      procedure. This delayed subtotal coronary obstruction was detected by routine
      final transesophageal echocardiographic examination. Emergency implantation of a
      coronary stent eliminated myocardial ischemia. This case demonstrated that
      coronary artery obstruction can occur not only during the TAVI procedure but also
      some time later. This finding reinforces the idea that these patients must also
      be carefully evaluated in the early post-procedure period.

PMID- 21098422
TI  - Acute aortic dissection associated with undetected congenital bicuspid aortic
      valve and infective endocarditis diagnosed intraoperatively.
AB  - The congenital bicuspid aortic valve (BAV) is recognized as a cause of acute
      aortic dissection (AAD) and also as a risk factor for infective endocarditis (IE)
      especially ring abscess. We experienced a case of all these combined and operated
      emergently. A 59-year-old man was transferred to us, and emergent operation was
      indicated for AAD and aortic stenosis (AS) due to BAV. However, he was strongly
      suspected of also having IE during the operation and the procedure was changed to
      a modified Bentall's method. The diagnosis was confirmed by pathological
      examination postoperatively. He recovered well after postoperative antimicrobial
      therapy without recurrent infection. It is important to remember that BAV is a
      risk factor for not only AAD but also IE, which sometimes occurs simultaneously
      and requires an emergent operation due to high mortality.

PMID- 21098419
TI  - A longitudinal comparison of 5 preference-weighted health state classification
      systems in persons with intervertebral disk herniation.
AB  - OBJECTIVE: To assess the longitudinal validity of widely used preference-weighted
      measurement systems for economic studies of intervertebral disk herniation (IDH).
      METHODS: Using data at baseline and 1 year from 1000 Spine Patient Outcomes
      Research Trial (SPORT) participants with IDH and complete data, the authors
      considered the EQ-5D with UK and US values (EQ-5D-UK and EQ-5D-US), 2 versions of
      the Health Utilities Index (HUI3 and HUI2), the SF-6D, and a regression-estimated
      quality of well-being score (eQWB). Differences in mean change scores (MCS) were
      assessed using signed rank tests, and Spearman correlations were calculated for
      change scores by system pairs. Using the Oswestry Disability Index, symptom
      satisfaction, progress rating, and self-perceived health ratings as criterion
      measures, the authors tested for trend in MCS across levels of change in
      criteria. They calculated floor and ceiling effects, effect size (ES),
      standardized response mean, and minimal important difference estimates. RESULTS:
      All systems demonstrated linear trends with external criteria and moderate to
      strong correlations between systems. However, differences in performance were
      evident. SF-6D and eQWB were most responsive (ES: 1.9 and 2.3, respectively),
      whereas EQ-5D-US and EQ-5D-UK were least responsive (ES: 1.23/1.20). Ceiling and
      floor effects were noted for all systems within key dimensions and for EQ-5D-UK
      and EQ-5D-US for overall score. MCS ranged from 0.40 (0.38) for EQ-5D-UK to 0.13
      (0.09) for eQWB and differed significantly, except between EQ-5D-US and HUI2.
      CONCLUSIONS: This research supports the validity of all systems for measuring
      change in persons with IDH, without finding a clearly superior system. The unique
      characteristics of each system revealed in this study should guide system choice.

PMID- 21098423
TI  - Clinical and pathological features of high grade primary cardiac osteosarcoma.
AB  - Primary cardiac sarcomas are very rare. We report one case of primary cardiac
      osteosarcoma arising from the left atrium of a 42-year-old woman and analyze its
      clinical and pathological features. Histopathologic examination revealed the
      tumor was composed of massive osteoid and cartilaginous differentiation embedded
      in spindle and polygonal cells with marked cytological and nuclear pleomorphism.
      The patient was alive without recurrence or metastasis at 20 months after surgery
      without further adjuvant chemotherapy or radiotherapy.

PMID- 21098424
TI  - Mycotic superior mesenteric pseudoaneurysm draining into a vein.
AB  - A 46-year-old man with a medical history notable only for schizophrenia was
      admitted to hospital with complaints of general fatigue and high fever.
      Transthoracic echocardiography on day 6 after admission demonstrated a large
      vegetation (17 mm) on the anterior leaflet of the mitral valve with mild
      regurgitation and mild aortic regurgitation. The patient also complained of
      abdominal pain. Abdominal computed tomography showed a remarkable enlargement of
      the superior mesenteric artery aneurysm (SMAA). An excision of the SMAA and
      double valve replacement was performed, and the patient was administered a six
      week course of intravenous antibiotic therapy.

PMID- 21098425
TI  - Cerebral monitoring in patients undergoing carotid endarterectomy using a triple
      assessment technique.
AB  - OBJECTIVES: Selective shunting during carotid endarterectomy (CEA) is advocated
      to reduce shunt related stroke. Cerebral monitoring is essential for temporary
      carotid shunting. Many techniques are available for cerebral monitoring, however,
      none is superior to monitoring the patient's neurological status (awake testing)
      while performing the procedure under local anaesthesia (LA). Cerebral oximetry
      (CO) and trans-cranial Doppler (TCD) has previously been used to show the
      adequacy of cerebral circulation in patients undergoing CEA. The aim of this
      study is to assess the reliability of CO and TCD in predicting the need for
      shunting compared to the awake testing. METHODS: Patients scheduled for CEA under
      LA were included. Patients converted to general anaesthesia (GA) and patients
      with no TCD window were excluded from the study. The Somanetics INVOS((r)) CO was
      used for ipsilateral cerebral monitoring in all patients, in addition to TCD and
      awake testing. The percentage fall in CO regional oxygen saturation (rSO(2)), and
      decline in the mean flow velocity (FVm) in TCD following carotid artery clamping
      recorded. A drop in rSO(2) of >=20% or FVm of >=50% was considered an indicator
      of cerebral ischaemia that may predict the need for carotid shunting. Patients
      only shunted based on awake testing. RESULTS: Forty-nine patients underwent
      triple assessment. The median clamp time was 24 min. 8/49 patients (16.3%) needed
      carotid shunting based on awake testing. In this group, six patients had >=20%
      drop in rSO(2), and >=50% drop in FVm. However, two patients had a non
      significant drop in both rSO(2) and FVm (false negative). In the non-shunted
      group (41/49), one patient had a significant drop in rSO(2) (false positive)
      while 10/41 patients had a >50% drop in FVm. This represents sensitivity of 75%,
      and specificity of 97.5% for CO compared to sensitivity of 75% and specificity of
      75% for TCD in prediction of shunting. The positive predictive value and negative
      predictive value were 85.7 and 95.2%, respectively for CO, compared to 37.5 and
      93.9% for TCD. CONCLUSIONS: TCD is less accurate than CO in predicting the need
      for carotid shunting during CEA. A combination of both methods does not add to
      the accuracy of detecting the need for carotid shunting.

PMID- 21098426
TI  - Primary results from the SmartDelay determined AV optimization: a comparison to
      other AV delay methods used in cardiac resynchronization therapy (SMART-AV)
      trial: a randomized trial comparing empirical, echocardiography-guided, and
      algorithmic atrioventricular delay programming in cardiac resynchronization
      therapy.
AB  - BACKGROUND: one variable that may influence cardiac resynchronization therapy
      response is the programmed atrioventricular (AV) delay. The SmartDelay determined
      av optimization: a comparison to other AV delay methods used in cardiac
      resynchronization therapy (SMART-AV) trial prospectively randomized patients to a
      fixed empirical AV delay (120 milliseconds), echocardiographically optimized AV
      delay, or AV delay optimized with SmartDelay, an electrogram-based algorithm.
      METHODS AND RESULTS: a total of 1014 patients (68% men; mean age, 66 +/- 11
      years; mean left ventricular ejection fraction, 25 +/- 7%) who met enrollment
      criteria received a cardiac resynchronization therapy defibrillator, and 980
      patients were randomized in a 1:1:1 ratio. All patients were programmed (DDD-60
      or DDDR-60) and evaluated after implantation and 3 and 6 months later. The
      primary end point was left ventricular end-systolic volume. Secondary end points
      included New York Heart Association class, quality-of-life score, 6-minute walk
      distance, left ventricular end-diastolic volume, and left ventricular ejection
      fraction. The medians (quartiles 1 and 3) for change in left ventricular end
      systolic volume at 6 months for the SmartDelay, echocardiography, and fixed arms
      were -21 mL (-45 and 6 mL), -19 mL (-45 and 6 mL), and -15 mL (-41 and 6 mL),
      respectively. No difference in improvement in left ventricular end-systolic
      volume at 6 months was observed between the SmartDelay and echocardiography arms
      (P=0.52) or the SmartDelay and fixed arms (P=0.66). Secondary end points,
      including structural (left ventricular end-diastolic volume and left ventricular
      ejection fraction) and functional (6-minute walk, quality of life, and New York
      Heart Association classification) measures, were not significantly different
      between arms. CONCLUSIONS: neither SmartDelay nor echocardiography was superior
      to a fixed AV delay of 120 milliseconds. The routine use of AV optimization
      techniques assessed in this trial is not warranted. However, these data do not
      exclude possible utility in selected patients who do not respond to cardiac
      resynchronization therapy.

PMID- 21098427
TI  - 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic
      adults: executive summary: a report of the American College of Cardiology
      Foundation/American Heart Association Task Force on Practice Guidelines.

PMID- 21098428
TI  - 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic
      adults: a report of the American College of Cardiology Foundation/American Heart
      Association Task Force on Practice Guidelines.

PMID- 21098429
TI  - Hospital certification for optimizing cardiovascular disease and stroke quality
      of care and outcomes.
AB  - Cardiovascular disease and stroke remain leading causes of mortality, disability,
      and rising healthcare expenditures in the United States. Although a number of
      organizations provide hospital accreditation, recognition, and certification
      programs, existing programs do not address cardiovascular disease and stroke care
      in a comprehensive way. Current evidence suggests mixed findings for correlation
      between accreditation, recognition, and certification programs and hospitals'
      actual quality of care and outcomes. This advisory discusses potential
      opportunities to develop and enhance hospital certification programs for
      cardiovascular disease and stroke. The American Heart Association/American Stroke
      Association is uniquely positioned as a patient-centered, respected, transparent
      healthcare organization to help drive improvements in care and outcomes for
      patients hospitalized with cardiovascular disease and stroke. As a part of its
      commitment to promoting high-quality, evidence-based care for cardiovascular and
      stroke patients, it is recommended that the American Heart Association/American
      Stroke Association explore hospital certification programs to develop truly
      meaningful programs to facilitate improvements in and recognition for
      cardiovascular disease and stroke quality of care and outcomes. Future strategies
      should standardize objective, unbiased assessments of hospital structural,
      process, and outcome performance while allowing flexibility as technology and
      methodology advances occur.

PMID- 21098430
TI  - SLIM: a sliding linear model for estimating the proportion of true null
      hypotheses in datasets with dependence structures.
AB  - MOTIVATION: The pre-estimate of the proportion of null hypotheses (pi(0)) plays a
      critical role in controlling false discovery rate (FDR) in multiple hypothesis
      testing. However, hidden complex dependence structures of many genomics datasets
      distort the distribution of p-values, rendering existing pi(0) estimators less
      effective. RESULTS: From the basic non-linear model of the q-value method, we
      developed a simple linear algorithm to probe local dependence blocks. We
      uncovered a non-static relationship between tests' p-values and their
      corresponding q-values that is influenced by data structure and pi(0). Using an
      optimization framework, these findings were exploited to devise a Sliding Linear
      Model (SLIM) to more reliably estimate pi(0) under dependence. When tested on a
      number of simulation datasets with varying data dependence structures and on
      microarray data, SLIM was found to be robust in estimating pi(0) against
      dependence. The accuracy of its pi(0) estimation suggests that SLIM can be used
      as a stand-alone tool for prediction of significant tests. AVAILABILITY: The R
      code of the proposed method is available at http://aspendb.uga.edu/downloads for
      academic use.

PMID- 21098431
TI  - Paintomics: a web based tool for the joint visualization of transcriptomics and
      metabolomics data.
AB  - MOTIVATION: The development of the omics technologies such as transcriptomics,
      proteomics and metabolomics has made possible the realization of systems biology
      studies where biological systems are interrogated at different levels of
      biochemical activity (gene expression, protein activity and/or metabolite
      concentration). An effective approach to the analysis of these complex datasets
      is the joined visualization of the disparate biomolecular data on the framework
      of known biological pathways. RESULTS: We have developed the Paintomics web
      server as an easy-to-use bioinformatics resource that facilitates the integrated
      visual analysis of experiments where transcriptomics and metabolomics data have
      been measured on different conditions for the same samples. Basically, Paintomics
      takes complete transcriptomics and metabolomics datasets, together with lists of
      significant gene or metabolite changes, and paints this information on KEGG
      pathway maps. AVAILABILITY: Paintomics is freely available at
      http://www.paintomics.org.

PMID- 21098432
TI  - Improving structure alignment-based prediction of SCOP families using Vorolign
      kernels.
AB  - MOTIVATION: The slow growth of expert-curated databases compared to experimental
      databases makes it necessary to build upon highly accurate automated processing
      pipelines to make the most of the data until curation becomes available. We
      address this problem in the context of protein structures and their
      classification into structural and functional classes, more specifically, the
      structural classification of proteins (SCOP). Structural alignment methods like
      Vorolign already provide good classification results, but effectively work in a 1
      Nearest Neighbor mode. Model-based (in contrast to instance-based) approaches so
      far have been shown to be of limited values due to small classes arising in such
      classification schemes. RESULTS: In this article, we describe how kernels defined
      in terms of Vorolign scores can be used in SVM learning, and explore variants of
      combined instance-based and model-based learning, up to exclusively model-based
      learning. Our results suggest that kernels based on Vorolign scores are effective
      and that model-based learning can yield highly competitive classification results
      for the prediction of SCOP families. AVAILABILITY: The code is made available at:
      http://wwwkramer.in.tum.de/research/applications/vorolign-kernel.

PMID- 21098433
TI  - Prognostic transcriptional association networks: a new supervised approach based
      on regression trees.
AB  - MOTIVATION: The application of information encoded in molecular networks for
      prognostic purposes is a crucial objective of systems biomedicine. This approach
      has not been widely investigated in the cardiovascular research area. Within this
      area, the prediction of clinical outcomes after suffering a heart attack would
      represent a significant step forward. We developed a new quantitative prediction
      based method for this prognostic problem based on the discovery of clinically
      relevant transcriptional association networks. This method integrates regression
      trees and clinical class-specific networks, and can be applied to other clinical
      domains. RESULTS: Before analyzing our cardiovascular disease dataset, we tested
      the usefulness of our approach on a benchmark dataset with control and disease
      patients. We also compared it to several algorithms to infer transcriptional
      association networks and classification models. Comparative results provided
      evidence of the prediction power of our approach. Next, we discovered new models
      for predicting good and bad outcomes after myocardial infarction. Using blood
      derived gene expression data, our models reported areas under the receiver
      operating characteristic curve above 0.70. Our model could also outperform
      different techniques based on co-expressed gene modules. We also predicted
      processes that may represent novel therapeutic targets for heart disease, such as
      the synthesis of leucine and isoleucine. AVAILABILITY: The SATuRNo software is
      freely available at http://www.lsi.us.es/isanepo/toolsSaturno/.

PMID- 21098434
TI  - Inhibition of hyaluronan synthesis accelerates murine atherosclerosis: novel
      insights into the role of hyaluronan synthesis.
AB  - BACKGROUND: Hyaluronan is thought to mediate neointimal hyperplasia but also
      vasoprotection as an integral component of the endothelial glycocalyx. The
      present study addressed for the first time the effects of long-term
      pharmacological inhibition of hyaluronan synthesis on vascular function and
      atherosclerosis. METHODS AND RESULTS: Four-week-old apolipoprotein E-deficient
      mice on a Western diet received orally an inhibitor of hyaluronan synthesis, 4
      methylumbelliferone (4-MU; 10 mg/g body wt), resulting in 600 nmol/L 4-MU in
      plasma. As a result, aortic plaque burden was markedly increased at 25 weeks.
      Furthermore, acetylcholine-dependent relaxation of aortic rings was decreased and
      mean arterial blood pressure was increased in response to 4-MU. However,
      hydralazine blunted the hypertensive effect of 4-MU without inhibiting the
      proatherosclerotic effect. A photothrombosis model revealed a prothrombotic state
      that was not due to increased platelet activation or increased thrombin
      activation as monitored by CD62P expression and the endogenous thrombin
      potential. Importantly, increased recruitment of macrophages to vascular lesions
      was detected after 2 and 21 weeks of 4-MU treatment by immunohistochemistry, by
      intravital microscopy, and in a peritonitis model. As a potential underlying
      mechanism, severe damage of the endothelial glycocalyx after 2 and 21 weeks of
      treatment with 4-MU was detected by electron microscopy of the innominate artery
      and myocardial capillaries. Furthermore, 600 nmol/L 4-MU inhibited hyaluronan
      synthesis in cultured endothelial cells. CONCLUSIONS: The data suggest that
      systemic inhibition of hyaluronan synthesis by 4-MU interferes with the
      protective function of the endothelial glycocalyx, thereby facilitating leukocyte
      adhesion, subsequent inflammation, and progression of atherosclerosis.

PMID- 21098435
TI  - Cryoablation versus radiofrequency energy for the ablation of atrioventricular
      nodal reentrant tachycardia (the CYRANO Study): results from a large multicenter
      prospective randomized trial.
AB  - BACKGROUND: Cryoablation has emerged as an alternative to radiofrequency catheter
      ablation (RFCA) for the treatment of atrioventricular (AV) nodal reentrant
      tachycardia (AVNRT). The purpose of this prospective randomized study was to test
      whether cryoablation is as effective as RFCA during both short-term and long-term
      follow-up with a lower risk of permanent AV block. METHODS AND RESULTS: A total
      of 509 patients underwent slow pathway cryoablation (n=251) or RFCA (n=258). The
      primary end point was immediate ablation failure, permanent AV block, and AVNRT
      recurrence during a 6-month follow-up. Secondary end points included procedural
      parameters, device functionality, and pain perception. Significantly more
      patients in the cryoablation group than the RFCA group reached the primary end
      point (12.6% versus 6.3%; P=0.018). Whereas immediate ablation success (96.8%
      versus 98.4%) and occurrence of permanent AV block (0% versus 0.4%) did not
      differ, AVNRT recurrence was significantly more frequent in the cryoablation
      group (9.4% versus 4.4%; P=0.029). In the cryoablation group, procedure duration
      was longer (138+/-54 versus 123+/-48 minutes; P=0.0012) and more device problems
      occurred (13 versus 2 patients; P=0.033). Pain perception was lower in the
      cryoablation group (P<0.001). CONCLUSIONS: Cryoablation for AVNRT is as effective
      as RFCA over the short term but is associated with a higher recurrence rate at
      the 6-month follow-up. The risk of permanent AV block does not differ
      significantly between cryoablation and RFCA. The potential benefits of cryoenergy
      relative to ablation safety and pain perception are counterbalanced by longer
      procedure times, more device problems, and a high recurrence rate. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00196222.

PMID- 21098436
TI  - Evaluation of the second generation of a bioresorbable everolimus drug-eluting
      vascular scaffold for treatment of de novo coronary artery stenosis: six-month
      clinical and imaging outcomes.
AB  - BACKGROUND: The first generation of the bioresorbable everolimus drug-eluting
      vascular scaffold showed signs of shrinkage at 6 months, which largely
      contributed to late luminal loss. Nevertheless, late luminal loss was less than
      that observed with bare metal stents. To maintain the mechanical integrity of the
      device up to 6 months, the scaffold design and manufacturing process of its
      polymer were modified. METHODS AND RESULTS: Quantitative coronary angiography,
      intravascular ultrasound with analysis of radiofrequency backscattering, and as
      an optional assessment, optical coherence tomography (OCT) were performed at
      baseline and at a 6-month follow-up. Forty-five patients successfully received a
      single bioresorbable everolimus drug-eluting vascular scaffold. One patient had
      postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient
      with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation
      was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3
      patients declined recatheterization, 42 patients had quantitative coronary
      angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT.
      Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in
      segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen
      with the first generation of bioresorbable everolimus drug-eluting vascular
      scaffold at 6 months, the backscattering of the polymeric struts did not decrease
      over time, the scaffold area was reduced by only 2.0% with intravascular
      ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the
      late lumen loss amounted to 0.19+/-0.18 mm with a limited relative decrease in
      minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up
      that 96.8% of the struts were covered and that malapposition of at least 1 strut,
      initially observed in 12 scaffolds, was detected at follow-up in only 3
      scaffolds. Mean neointimal growth measured by OCT between and on top of the
      polymeric struts equaled 1.25 mm(2), or 16.6% of the scaffold area. CONCLUSION:
      Modified manufacturing process of the polymer and geometric changes in the
      polymeric platform have substantially improved the medium-term performance of
      this new generation of drug-eluting scaffold to become comparable to those of
      current drug eluting stents. CLINICAL TRIAL REGISTRATION: URL:
      http://clinicaltrials.gov. Unique identifier: NCT00856856.

PMID- 21098437
TI  - Prevalence and clinical significance of papillary muscle infarction detected by
      late gadolinium-enhanced magnetic resonance imaging in patients with ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: The frequency of papillary muscle infarction (PapMI) without rupture
      has not been fully investigated in vivo. Furthermore, the relationship between
      papillary muscle dysfunction and mitral regurgitation (MR) has been controversial
      in patients with ST-segment elevation myocardial infarction. Therefore, the aim
      of this study was to assess the frequency and clinical characteristics of PapMI
      without rupture using late gadolinium-enhanced magnetic resonance imaging (MRI)
      in patients with ST-segment elevation myocardial infarction. METHODS AND RESULTS:
      One hundred eighteen ST-segment elevation myocardial infarction patients with
      primary percutaneous coronary intervention underwent cardiac MRI twice 9+/-4 days
      and 8+/-1 months (n=104) after myocardial infarction. MR was categorized by
      echocardiography. Of these patients, 40% were found to have late gadolinium
      enhancement of papillary muscle, in which the posterior papillary muscle was
      involved more frequently than the anterior papillary muscle (77% versus 26%;
      P<0.001). PapMI was encountered more frequently in patients with left circumflex
      and right coronary artery lesions compared with left anterior descending artery
      lesion (78%, 48%, and 13%; P<0.001). By multiple logistic regression analysis,
      only coaptation height was identified as an independent predictor of the presence
      of MR. The second cardiac magnetic resonance imaging showed that the infarct size
      had a positive correlation with left ventricular end-diastolic volume (r=0.41,
      P<0.001) and that PapMI was not associated with left ventricular remodeling
      (P=0.31). Deterioration of MR was not observed in patients with PapMI.
      CONCLUSIONS: PapMI is more frequent than previously thought yet appears to have
      significant clinical latency. The size of the myocardial infarction, but not the
      presence of PapMI, seems to affect left ventricular remodeling, and PapMI is not
      obligatorily associated with MR.

PMID- 21098438
TI  - Bioresorbable stents: the next revolution.

PMID- 21098439
TI  - Adverse bioenergetic consequences of Na+-Ca2+ exchanger-mediated Ca2+ influx in
      cardiac myocytes.
AB  - BACKGROUND: In heart failure, the Na+-Ca2+ exchanger (NCX) is upregulated and
      mediates Ca2+ influx (instead of efflux) during the cardiac action potential.
      Although this partly compensates for impaired sarcoplasmic reticulum Ca2+ release
      and supports inotropy, the energetic consequences have never been considered.
      Because NCX-mediated Ca2+ influx is rather slow and mitochondrial Ca2+ uptake
      (which stimulates NADH production by the Krebs cycle) is thought to be
      facilitated by high Ca2+ gradients in a "mitochondrial Ca2+ microdomain," we
      speculated that NCX-mediated Ca2+ influx negatively affects the bioenergetic
      feedback response. Methods and Results- With the use of a patch-clamp-based
      approach in guinea-pig myocytes, cytosolic and mitochondrial Ca2+ ([Ca2+](c) and
      [Ca2+](m), respectively) was determined within the same cell after varying Ca2+
      influx via L-type Ca2+ channels (I(Ca,L)) or the NCX. The efficiency of
      mitochondrial Ca2+ uptake, indexed by the slope of plotting [Ca2+](m) against
      [Ca2+](c) during each Ca2+ transient, was maximal during I(Ca,L)-triggered
      sarcoplasmic reticulum Ca2+ release. Depletion of sarcoplasmic reticulum Ca2+
      load and increased contribution of the NCX to cytosolic Ca2+ influx independently
      reduced the efficiency of mitochondrial Ca2+ uptake. The upstroke velocity of
      cytosolic Ca2+ transients closely correlated with the efficiency of mitochondrial
      Ca2+ uptake. Despite comparable [Ca2+](c), sarcoplasmic reticulum Ca2+ release,
      but not NCX-mediated Ca2+ influx, led to stimulation of Ca2+-sensitive
      dehydrogenases of the Krebs cycle. Conclusions- Increased contribution of the NCX
      to cytosolic Ca2+ transients, which occurs in cardiac myocytes from failing
      hearts, impairs mitochondrial Ca2+ uptake and the bioenergetic feedback response.
      This mechanism could contribute to energy starvation of failing hearts.

PMID- 21098440
TI  - Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase
      II promotes life-threatening ventricular arrhythmias in mice with heart failure.
AB  - BACKGROUND: approximately half of patients with heart failure die suddenly as a
      result of ventricular arrhythmias. Although abnormal Ca(2+) release from the
      sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to
      arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic
      Ca(2+) remain unknown. We tested the hypothesis that increased RyR2
      phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both
      necessary and sufficient to promote lethal ventricular arrhythmias. METHODS AND
      RESULTS: mice in which the S2814 Ca(2+)/calmodulin-dependent protein kinase II
      site on RyR2 is constitutively activated (S2814D) develop pathological
      sarcoplasmic reticulum Ca(2+) release events, resulting in reduced sarcoplasmic
      reticulum Ca(2+) load on confocal microscopy. These Ca(2+) release events are
      associated with increased RyR2 open probability in lipid bilayer preparations. At
      baseline, young S2814D mice have structurally and functionally normal hearts
      without arrhythmias; however, they develop sustained ventricular tachycardia and
      sudden cardiac death on catecholaminergic provocation by caffeine/epinephrine or
      programmed electric stimulation. Young S2814D mice have a significant
      predisposition to sudden arrhythmogenic death after transverse aortic
      constriction surgery. Finally, genetic ablation of the Ca(2+)/calmodulin
      dependent protein kinase II site on RyR2 (S2814A) protects mutant mice from
      pacing-induced arrhythmias versus wild-type mice after transverse aortic
      constriction surgery. CONCLUSIONS: our results suggest that Ca(2+)/calmodulin
      dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at
      S2814 plays an important role in arrhythmogenesis and sudden cardiac death in
      mice with heart failure.

PMID- 21098441
TI  - Novel chemical suppressors of long QT syndrome identified by an in vivo
      functional screen.
AB  - BACKGROUND: Genetic long QT (LQT) syndrome is a life-threatening disorder caused
      by mutations that result in prolongation of cardiac repolarization. Recent work
      has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates
      several features of human disease, including prolongation of ventricular action
      potential duration, spontaneous early afterdepolarizations, and 2:1
      atrioventricular block in early stages of development. Because of their
      transparency, small size, and absorption of small molecules from their
      environment, zebrafish are amenable to high-throughput chemical screens. We
      describe a small-molecule screen using the zebrafish KCNH2 mutant breakdance to
      identify compounds that can rescue the LQT type 2 phenotype. METHODS AND RESULTS:
      Zebrafish breakdance embryos were exposed to test compounds at 48 hours of
      development and scored for rescue of 2:1 atrioventricular block at 72 hours in a
      96-well format. Only compounds that suppressed the LQT phenotype in 3 of 3 fish
      were considered hits. Screen compounds were obtained from commercially available
      small-molecule libraries (Prestwick and Chembridge). Initial hits were confirmed
      with dose-response testing and time-course studies. Optical mapping with the
      voltage-sensitive dye di-4 ANEPPS was performed to measure compound effects on
      cardiac action potential durations. Screening of 1200 small molecules resulted in
      the identification of flurandrenolide and 2-methoxy-N-(4-methylphenyl) benzamide
      (2-MMB) as compounds that reproducibly suppressed the LQT phenotype. Optical
      mapping confirmed that treatment with each compound caused shortening of
      ventricular action potential durations. Structure activity studies and steroid
      receptor knockdown suggest that flurandrenolide functions via the glucocorticoid
      signaling pathway. CONCLUSIONS: Using a zebrafish model of LQT type 2 syndrome in
      a high-throughput chemical screen, we have identified 2 compounds,
      flurandrenolide and the novel compound 2-MMB, as small molecules that rescue the
      zebrafish LQT type 2 syndrome by shortening the ventricular action potential
      duration. We provide evidence that flurandrenolide functions via the
      glucocorticoid receptor-mediated pathway. These 2 molecules and future
      discoveries from this screen should yield novel tools for the study of cardiac
      electrophysiology and may lead to novel therapeutics for human LQT patients.

PMID- 21098442
TI  - Intracoronary versus intravenous administration of abciximab in patients with ST
      segment elevation myocardial infarction undergoing primary percutaneous coronary
      intervention with thrombus aspiration: the comparison of intracoronary versus
      intravenous abciximab administration during emergency reperfusion of ST-segment
      elevation myocardial infarction (CICERO) trial.
AB  - BACKGROUND: administration of the glycoprotein IIb/IIIa inhibitor abciximab is an
      effective adjunctive treatment strategy during primary percutaneous coronary
      intervention for ST-segment elevation myocardial infarction. Although small-scale
      studies have suggested beneficial effects of intracoronary over intravenous
      administration of abciximab, this has not been investigated in a medium-scale
      randomized clinical trial. METHODS AND RESULTS: a total of 534 ST-segment
      elevation myocardial infarction patients undergoing primary percutaneous coronary
      intervention with thrombus aspiration within 12 hours of symptom onset were
      randomized to either an intracoronary or an intravenous bolus of abciximab (0.25
      mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The
      primary end point was the incidence of restored myocardial reperfusion, defined
      as complete ST-segment resolution. Secondary end points included myocardial
      reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and
      major adverse cardiac events at 30 days. The incidence of complete ST-segment
      resolution was similar in the intracoronary and intravenous groups (64% versus
      62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in
      the intracoronary group than in the intravenous group (76% versus 67%; P=0.022).
      Furthermore, enzymatic infarct size was smaller in the intracoronary than in the
      intravenous group (P=0.008). The incidence of major adverse cardiac events was
      similar in both groups (5.5% versus 6.1%; P=0.786). CONCLUSIONS: in ST-segment
      elevation myocardial infarction patients undergoing primary percutaneous coronary
      intervention with thrombus aspiration, intracoronary administration of abciximab
      compared with intravenous administration does not improve myocardial reperfusion
      as assessed by ST-segment resolution. However, intracoronary administration is
      associated with improved myocardial reperfusion as assessed by myocardial blush
      grade and a smaller enzymatic infarct size.

PMID- 21098443
TI  - Myocardial infarction and risk of suicide: a population-based case-control study.
AB  - BACKGROUND: Myocardial infarction (MI) is associated with an increased risk of
      anxiety, depression, low quality of life, and all-cause mortality. Whether MI is
      associated with an increased risk of suicide is unknown. We examined the
      association between MI and suicide. METHODS AND RESULTS: We conducted a
      population-based case-control study by retrieving data from 5 nationwide
      longitudinal registers in Denmark. As cases, we selected all persons aged 40 to
      89 years who died by suicide from 1981 to 2006. As controls, we randomly selected
      up to 10 persons per case matched by sex, day of birth, and calendar time. We
      identified 19,857 persons who committed suicide and 190,058 controls. MI was
      associated with a marked increased risk of suicide. The risk of suicide was
      highest during the first month after discharge for MI for patients with no
      history of psychiatric illness (adjusted rate ratio, 3.25; 95% confidence
      interval, 1.61 to 6.56) and for patients with a history of psychiatric illness
      (adjusted rate ratio, 64.05; 95% confidence interval, 13.36 to 307.06) compared
      with those with no history of MI or psychiatric illness. However, the risk
      remained high for at least 5 years after MI. CONCLUSIONS: MI is followed by an
      increased risk of suicide for persons with and without psychiatric illness. Our
      results suggest the importance of screening patients with MI for depression and
      suicidal ideation.

PMID- 21098444
TI  - Temporal trends in survival to adulthood among patients born with congenital
      heart disease from 1970 to 1992 in Belgium.
AB  - BACKGROUND: Over the past decades, the life expectancy of individuals with
      congenital heart disease (CHD) has increased significantly. However, precise
      estimates for survival to adulthood are scarce for patients with CHD. We
      investigated the proportion of CHD patients born between 1990 and 1992 who
      survived into adulthood. We also compared their survival with that of CHD
      patients born in earlier eras and evaluated survival as a function of the type of
      heart defect. METHODS AND RESULTS: We reviewed the CHD program administrative and
      clinical database at the University Hospitals Leuven (Leuven, Belgium) and
      analyzed the records of 7497 CHD patients born from 1970 to 1992. Survival to 18
      years of age in patients born between 1990 and 1992 was 88.6% (95% confidence
      interval [CI], 86.3% to 90.5%), which was significantly greater than that of
      patients born in previous decades (P<0.0001). For patients born between 1990 and
      1992, survival into adulthood for those with mild heart defects was 98.0% (95%
      CI, 95.8% to 99.1%), whereas survival for those with moderate- and severe
      complexity heart defects was 90.0% (95% CI, 86.8% to 92.5%) and 56.4% (95% CI,
      47.4% to 64.5%), respectively. Analysis per heart defect confirmed these
      findings, demonstrating that patients with univentricular heart (49.1% [95% CI,
      30.8% to 65.1%]) and hypoplastic left heart syndrome (7.5% [95% CI, 0.6% to
      26.6%]) had the poorest survival rate. CONCLUSION: This study demonstrates that
      almost 90% of children with CHD have the prospect of surviving into adulthood.

PMID- 21098445
TI  - Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and
      limits their long-term benefits for myocardial repair.
AB  - BACKGROUND: Cardiac cell therapy for older patients who experience a myocardial
      infarction may require highly regenerative cells from young, healthy (allogeneic)
      donors. Bone marrow mesenchymal stem cells (MSCs) are currently under clinical
      investigation because they can induce cardiac repair and may also be
      immunoprivileged (suitable for allogeneic applications). However, it is unclear
      whether allogeneic MSCs retain their immunoprivilege or functional efficacy late
      after myocardial implantation. We evaluated the effects of MSC differentiation on
      the immune characteristics of cells in vitro and in vivo and monitored cardiac
      function for 6 months after post-myocardial infarction MSC therapy. METHODS AND
      RESULTS: In the in vitro experiments, inducing MSCs to acquire myogenic,
      endothelial, or smooth muscle characteristics (via 5-azacytidine or cytokine
      treatment) increased major histocompatibility complex-Ia and -II (immunogenic)
      expression and reduced major histocompatibility complex-Ib (immunosuppressive)
      expression, in association with increased cytotoxicity in coculture with
      allogeneic leukocytes. In the in vivo experiments, we implanted allogeneic or
      syngeneic MSCs into infarcted rat myocardia. We measured cell differentiation and
      survival (immunohistochemistry, real-time polymerase chain reaction) and cardiac
      function (echocardiography, pressure-volume catheter) for 6 months. MSCs (versus
      media) significantly improved ventricular function for at least 3 months after
      implantation. Allogeneic (but not syngeneic) cells were eliminated from the heart
      by 5 weeks after implantation, and their functional benefits were lost within 5
      months. CONCLUSIONS: The long-term ability of allogeneic MSCs to preserve
      function in the infarcted heart is limited by a biphasic immune response whereby
      they transition from an immunoprivileged to an immunogenic state after
      differentiation, which is associated with an alteration in major
      histocompatibility complex-immune antigen profile.

PMID- 21098446
TI  - MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation.
AB  - BACKGROUND: A characteristic of both clinical and experimental atrial
      fibrillation (AF) is atrial electric remodeling associated with profound
      reduction of L-type Ca(2+) current and shortening of the action potential
      duration. The possibility that microRNAs (miRNAs) may be involved in this process
      has not been tested. Accordingly, we assessed the potential role of miRNAs in
      regulating experimental AF. METHODS AND RESULTS: The miRNA transcriptome was
      analyzed by microarray and verified by real-time reverse-transcription polymerase
      chain reaction with left atrial samples from dogs with AF established by right
      atrial tachypacing for 8 weeks and from human atrial samples from AF patients
      with rheumatic heart disease. miR-223, miR-328, and miR-664 were found to be
      upregulated by >2 fold, whereas miR-101, miR-320, and miR-499 were downregulated
      by at least 50%. In particular, miR-328 level was elevated by 3.9-fold in AF dogs
      and 3.5-fold in AF patients relative to non-AF subjects. Computational prediction
      identified CACNA1C and CACNB1, which encode cardiac L-type Ca(2+) channel alpha1c
      and beta1 subunits, respectively, as potential targets for miR-328. Forced
      expression of miR-328 through adenovirus infection in canine atrium and
      transgenic approach in mice recapitulated the phenotypes of AF, exemplified by
      enhanced AF vulnerability, diminished L-type Ca(2+) current, and shortened atrial
      action potential duration. Normalization of miR-328 level with antagomiR reversed
      the conditions, and genetic knockdown of endogenous miR-328 dampened AF
      vulnerability. CACNA1C and CACNB1 as the cognate target genes for miR-328 were
      confirmed by Western blot and luciferase activity assay showing the reciprocal
      relationship between the levels of miR-328 and L-type Ca(2+) channel protein
      subunits. CONCLUSIONS: miR-328 contributes to the adverse atrial electric
      remodeling in AF through targeting L-type Ca(2+) channel genes. The study
      therefore uncovered a novel molecular mechanism for AF and indicated miR-328 as a
      potential therapeutic target for AF.

PMID- 21098447
TI  - Mortality resulting from congenital heart disease among children and adults in
      the United States, 1999 to 2006.
AB  - BACKGROUND: Previous reports suggest that mortality resulting from congenital
      heart disease (CHD) among infants and young children has been decreasing. There
      is little population-based information on CHD mortality trends and patterns among
      older children and adults. METHODS AND RESULTS: We used data from death
      certificates filed in the United States from 1999 to 2006 to calculate annual CHD
      mortality by age at death, race-ethnicity, and sex. To calculate mortality rates
      for individuals >=1 year of age, population counts from the US Census were used
      in the denominator; for infant mortality, live birth counts were used. From 1999
      to 2006, there were 41,494 CHD-related deaths and 27,960 deaths resulting from
      CHD (age-standardized mortality rates, 1.78 and 1.20 per 100,000, respectively).
      During this period, mortality resulting from CHD declined 24.1% overall.
      Mortality resulting from CHD significantly declined among all race-ethnicities
      studied. However, disparities persisted; overall and among infants, mortality
      resulting from CHD was consistently higher among non-Hispanic blacks compared
      with non-Hispanic whites. Infant mortality accounted for 48.1% of all mortality
      resulting from CHD; among those who survived the first year of life, 76.1% of
      deaths occurred during adulthood (>=18 years of age). CONCLUSIONS: CHD mortality
      continued to decline among both children and adults; however, differences between
      race-ethnicities persisted. A large proportion of CHD-related mortality occurred
      during infancy, although significant CHD mortality occurred during adulthood,
      indicating the need for adult CHD specialty management.

PMID- 21098448
TI  - Myocardial perfusion scans: projected population cancer risks from current levels
      of use in the United States.
AB  - BACKGROUND: Myocardial perfusion scans contribute up to 20% of the estimated
      annual collective radiation dose to the US population. We estimated potential
      future cancer risk from these scans by age at exposure and current frequency of
      use in the United States. METHODS AND RESULTS: Usage patterns were determined
      from national survey data, and radionuclide dosage was based on current
      guidelines. Cancer risk projection models were generated on the basis of the
      National Research Council Biological Effects of Ionizing Radiation VII report,
      under the assumption that risk has a linear relationship with radiation exposure
      even at low doses. The mean projected number of radiation-related incident
      cancers and 95% uncertainty intervals were estimated with the use of Monte Carlo
      simulations. Estimated risks for a scan performed at age 50 years ranged from 2
      cancers per 10,000 scans (95% uncertainty interval, 1 to 5) for a positron
      emission tomography ammonia-13 test to 25 cancers per 10,000 scans (95%
      uncertainty interval, 9 to 58) for a dual-isotope (thallium-201 plus technetium
      99m) scan. Risks were 50% lower at age 70 years but were similar for men and
      women. The combination of cancer risk estimates and data on frequency of use
      suggests that the 9.1 million myocardial perfusion scans performed annually in
      the United States could result in 7400 (95% uncertainty interval, 3300 to 13,700)
      additional future cancers. CONCLUSIONS: The lifetime cancer risk from a single
      myocardial perfusion scan is small and should be balanced against likely benefit
      and appropriateness of the test. The estimates depend on a number of assumptions,
      including life expectancy. They apply directly to asymptomatic individuals with
      life expectancies similar to those of the general population. For individuals
      with a symptomatic clinical profile, on whom such scans are typically performed,
      the risks will be lower because of shorter life expectancy.

PMID- 21098449
TI  - The sPLA2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary
      Intervention (SPIDER-PCI) trial.
AB  - BACKGROUND: Secretory phospholipase A(2) (sPLA(2)) may play a role in myonecrosis
      after elective percutaneous coronary intervention (PCI). Inhibition of this
      enzyme may have a beneficial effect. The central hypothesis of this study was
      that treatment with varespladib, a small-molecule inhibitor of sPLA(2) would
      reduce postprocedural release of cardiac biomarkers after elective percutaneous
      coronary intervention. METHODS AND RESULTS: Between October 2007 and June 2009,
      144 stable patients were randomized in a phase II trial to receive varespladib
      500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective
      percutaneous coronary intervention. The primary end point was elevation of
      troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18
      to 24 hours after percutaneous coronary intervention. Mean age was 63+/-10 and
      64+/-10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior
      myocardial infarction for the varespladib and placebo groups, respectively. The
      primary end point occurred in 75% of varespladib and 63% of placebo patients
      (P=0.14). Troponin I 3 times the upper limit of normal was observed in 57% and
      50% (P=0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and
      3% (P=0.018). Median (first and third quartiles) change in high-sensitivity C
      reactive protein in these 2 groups was 0.65 mg/L (-0.18 and 1.48) and 0.70 mg/L
      (0.00 and 1.50) at 18 to 24 hours (P=0.81) and 0.20 mg/L (-0.70 and 1.40) and
      0.60 mg/L (-0.12 and 1.72) at 3 to 5 days (P=0.23), whereas change in sPLA(2)
      activity at 3 to 5 days in a subset was -2.85 ng/ml (-3.40 and -1.85) and 0.25
      ng/ml (-0.20 and 0.85) (P<0.001). CONCLUSIONS: Inhibition of sPLA(2) by
      varespladib administered for 3 to 5 days before the procedure does not reduce
      periprocedural myonecrosis associated with elective percutaneous coronary
      intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00533039.

PMID- 21098450
TI  - Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons
      from a 5-year follow-up.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (AF) naturally progresses toward
      chronic AF at an estimated rate of 15% to 30% over a 1- to 3-year period.
      Pulmonary vein (PV) isolation is increasingly performed for the treatment of drug
      refractory paroxysmal AF. The long-term data on clinical outcome after
      circumferential PV isolation are limited. METHODS AND RESULTS: From 2003 to late
      2004, 161 patients (121 men; age, 59.8+/-9.7 years) with symptomatic paroxysmal
      AF and normal left ventricular function underwent circumferential PV isolation
      guided by 3-dimensional mapping and double Lasso technique. Right-sided and left
      sided continuous circular lesions encircling the ipsilateral PVs were placed with
      irrigated radiofrequency energy. The procedure end point was the absence of all
      PV spikes for at least 30 minutes after PV isolation verified by 2 Lasso
      catheters placed within the ipsilateral PVs. Sinus rhythm was present in 75
      patients (46.6%) after the initial procedure during a median follow-up period of
      4.8 years (0.33 to 5.5 years). A second procedure was performed in 66 and a third
      procedure in 12 patients. Recovered PV isolation conduction was observed in 62 of
      66 patients (94.0%) during the second and in 8 of 12 patients (66.7%) during the
      third procedure. After a median of 1 (1 to 3) procedure, stable sinus rhythm was
      achieved in 128 of 161 patients (79.5%), whereas clinical improvement occurred in
      an additional 21 of 161 patients (13.0%) during a median follow-up of 4.6 years
      (0.33 to 5.5 years). Four patients in stable sinus rhythm died during follow-up.
      Progression toward chronic AF was observed in 4 patients (2.4%); however, only 2
      patients reported symptoms. CONCLUSION: In patients with paroxysmal AF and normal
      left ventricular function, circumferential PV isolation results in stable sinus
      rhythm in the majority of patients, and low incidence of chronic AF was observed
      after ablation during up to 5 years of follow-up.

PMID- 21098451
TI  - Individualized assessment of radiation dose in patients undergoing coronary
      computed tomographic angiography with 256-slice scanning.
AB  - BACKGROUND: Available data on the radiation burden from coronary computed
      tomography (CT) angiography (CCTA) are mostly limited to effective dose
      estimates. This study provides individualized estimates of doses and associated
      life attributable risks of radiation-induced cancer in a clinical patient
      population undergoing 256-slice CCTA. METHODS AND RESULTS: Typical
      retrospectively and prospectively ECG-gated CCTA exposures in a 256-slice CT
      scanner were simulated on 52 patient-specific voxelized phantoms. Dose images
      depicting the dose deposition on the exposed region were generated, and
      normalized organ doses for all primarily irradiated radiosensitive organs were
      derived and correlated to patient body habitus. Lung, breast, and esophagus
      absorbed doses were then determined in 136 consecutive patients subjected to
      CCTA. Projected life attributable risks of radiation-induced cancer were
      estimated through the use of appropriate sex-, age- and organ-specific cancer
      risk factors and compared with corresponding nominal cancer risks. The total
      projected life attributable risk of radiogenic cancer after CCTA decreases
      steeply with age at exposure, and lung cancer constitutes the most probable
      detriment for both sexes. The relative risks of lung cancer associated with
      prospectively ECG-gated CCTA were 1.0032 and 1.0008 for women and men,
      respectively. The mean total projected life attributable risks were estimated to
      be 24.9+/-7.4 and 71.5+/-30.0 per 100,000 women undergoing prospectively and
      retrospectively ECG-gated CCTA, respectively. The corresponding values for men
      were 7.3+/-1.3 and 31.4+/-5.0 per 100 000 patients. CONCLUSIONS: The mean
      projected life attributable risks of radiation-induced cancer in a typical
      clinical patient cohort undergoing standard prospectively ECG-gated CCTA with a
      256-slice scanner were found to inconsequentially increase the natural cancer
      incidence rates.

PMID- 21098452
TI  - Long-term outcome after ICD and CRT implantation and influence of remote device
      follow-up: the ALTITUDE survival study.
AB  - BACKGROUND: Outcome data for patients receiving implantable cardioverter
      defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D)
      devices treated outside of clinical trials are lacking. No clinical trial has
      evaluated mortality after device implantation or after shock therapy in large
      numbers of patients with implanted devices that regularly transmit device data
      over a network. METHODS AND RESULTS: Survival status in patients implanted with
      ICD and CRT devices across the United States from a single manufacturer was
      assessed. Outcomes were compared between patients followed in device clinic
      settings and those who regularly transmit remote data collected from the device
      an average of 4 times monthly. Shock delivery and electrogram analysis could be
      ascertained from patients followed on the network, enabling survival after ICD
      shock to be evaluated. One- and 5-year survival rates in 185,778 patients after
      ICD implantation were 92% and 68% and were 88% and 54% for CRT-D device
      recipients. In 8228 patients implanted with CRT-only devices, survival was 82%
      and 48% at 1 and 5 years, respectively. For the 69,556 ICD and CRT-D patients
      receiving remote follow-up on the network, 1- and 5-year survival rates were
      higher compared with those in the 116,222 patients who received device follow-up
      in device clinics only (50% reduction; P<0.0001). There were no differences
      between patients followed on or off the remote network for the characteristics of
      age, gender, implanted device year or type, and economic or educational status.
      Shock therapy was associated with subsequent mortality risk for both ICD and CRT
      D recipients. CONCLUSIONS: Survival after ICD and CRT-D implantation in patients
      treated in naturalistic practice compares favorably with survival rates observed
      in clinical trials. Remote follow-up of device data is associated with excellent
      survival, but arrhythmias that result in device therapy in this population are
      associated with a higher mortality risk compared with patients who do not require
      shock therapy.

PMID- 21098453
TI  - Myocardial infarction and risk of suicide: another reason to develop and test
      ways to reduce distress in postmyocardial-infarction patients?

PMID- 21098454
TI  - Survival of patients with implantable cardioverter defibrillators in the era of
      remote-monitoring: the 5000-foot, high-altitude view.

PMID- 21098455
TI  - Myocarditic appearance of arrhythmogenic right ventricular cardiomyopathy.

PMID- 21098456
TI  - Letter by Antoniades et al regarding article, "Uncoupled cardiac nitric oxide
      synthase mediates diastolic dysfunction".

PMID- 21098459
TI  - Lipoprotein-associated and secreted phospholipases A2 in cardiovascular disease:
      roles as biological effectors and biomarkers.

PMID- 21098461
TI  - Adipositas cordis: an uncommon cardiomyopathy identified by cardiovascular
      magnetic resonance.

PMID- 21098460
TI  - Intensive glucose lowering and cardiovascular disease prevention in diabetes:
      reconciling the recent clinical trial data.

PMID- 21098463
TI  - Images in cardiovascular medicine. Interventricular septal hematoma and
      ventricular septal defect after retrograde intervention for a chronic total
      occlusion of a left anterior descending coronary artery.

PMID- 21098464
TI  - Letter by Correia and Barreto-Filho regarding article, "Predictors of outcomes in
      medically treated patients with acute coronary syndromes after angiographic
      triage: an Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY)
      Substudy".

PMID- 21098465
TI  - Letter by Boschetti et al regarding article, "Predictors of outcome in medically
      treated patients with acute coronary syndromes after angiographic triage: an
      Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Substudy".

PMID- 21098468
TI  - Pathophysiology of bleeding and clotting in the cardiac surgery patient: from
      vascular endothelium to circulatory assist device surface.

PMID- 21098469
TI  - The polypill in the prevention of cardiovascular diseases: key concepts, current
      status, challenges, and future directions.

PMID- 21098470
TI  - Abdominal wall venous collaterals: the latent clinical sign for central chronic
      venous obstruction.

PMID- 21098467
TI  - European ancestry as a risk factor for atrial fibrillation in African Americans.
AB  - BACKGROUND: Despite a higher burden of standard atrial fibrillation (AF) risk
      factors, African Americans have a lower risk of AF than whites. It is unknown
      whether the higher risk is due to genetic or environmental factors. Because
      African Americans have varying degrees of European ancestry, we sought to test
      the hypothesis that European ancestry is an independent risk factor for AF.
      METHODS AND RESULTS: We studied whites (n=4543) and African Americans (n=822) in
      the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans
      (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517).
      Percent European ancestry in African Americans was estimated with 1747 ancestry
      informative markers from the Illumina custom ITMAT-Broad-CARe array. Among
      African Americans without baseline AF, 120 of 804 CHS participants and 181 of
      3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies
      revealed that every 10% increase in European ancestry increased the risk of AF by
      13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After
      adjustment for potential confounders, European ancestry remained a predictor of
      incident AF in each cohort alone, with a combined estimated hazard ratio for each
      10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29;
      P=0.001). A second analysis using 3192 ancestry informative markers from a genome
      wide Affymetrix 6.0 array in ARIC African Americans yielded similar results.
      CONCLUSIONS: European ancestry predicted risk of incident AF. Our study suggests
      that investigating genetic variants contributing to differential AF risk in
      individuals of African versus European ancestry will be informative.

PMID- 21098471
TI  - Daily alcohol use and romantic relationship functioning: evidence of
      bidirectional, gender-, and context-specific effects.
AB  - Whether beneficial or harmful, cause or effect, the nature of associations
      between drinking and close relationship processes remains unclear. The present
      study examined these issues by using daily reports of alcohol use and
      relationship functioning from 69 heterosexual couples over 3 weeks. Multilevel
      modeling indicated that alcohol had both positive and negative effects on
      relationship processes and that effects were more positive for women, and when
      small amounts were consumed, partners drank together, or they consumed similar
      amounts. Interestingly, however, positive effects on intimacy and partner
      behaviors were not mediated by sexual contact. In the reverse direction, women
      were found to drink more than men in response to relationship difficulties and
      feeling disconnected from their partner (i.e., low intimacy). Overall findings
      indicate that associations between drinking and relationship processes are
      complex and bidirectional and that they may be more important for women than men.

PMID- 21098473
TI  - Changes in body mass alone explain almost all of the variance in the serum sodium
      concentrations during prolonged exercise. Has commercial influence impeded
      scientific endeavour?
AB  - In 1991, we provided definitive evidence that exercise-associated hyponatraemia
      (EAH) is caused by abnormal fluid retention in those who overdrink during
      prolonged exercise, but this finding was ignored. Instead, in 1996, influential
      guidelines of the American College of Sports Medicine (ACSM) promoted the concept
      that athletes should drink 'as much as tolerable' during exercise. What followed
      was an epidemic of cases of EAH and its associated encephalopathy (EAHE). A
      recent study funded by the sports drink industry confirms our 1991 finding by
      showing that 95% of the variance in the serum sodium concentration during
      exercise can be explained by changes in body mass alone. The possibility is that
      commercial influence delayed the acceptance of our findings for two decades.

PMID- 21098474
TI  - Understanding contradictory data in contraction stress tests.
AB  - The literature shows contradictory results regarding the role of composite
      shrinkage and elastic modulus as determinants of polymerization stress. The
      present study aimed at a better understanding of the test mechanics that could
      explain such divergences among studies. The hypothesis was that the effects of
      composite shrinkage and elastic modulus on stress depend upon the compliance of
      the testing system. A commonly used test apparatus was simulated by finite
      element analysis, with different compliance levels defined by the bonding
      substrate (steel, glass, composite, or acrylic). Composites with moduli between 1
      and 12 GPa and shrinkage values between 0.5% and 6% were modeled. Shrinkage was
      simulated by thermal analogy. The hypothesis was confirmed. When shrinkage and
      modulus increased simultaneously, stress increased regardless of the substrate.
      However, if shrinkage and modulus were inversely related, their magnitudes and
      interaction with rod material determined the stress response.

PMID- 21098475
TI  - Non-syndromic oligodontia with a novel mutation of PAX9.
AB  - Agenesis of the permanent teeth is a congenital anomaly that is frequently seen
      in humans. Oligodontia is a severe type of tooth agenesis involving 6 or more
      congenitally missing teeth, excluding the third molars. Previous studies have
      indicated that mutations in the homeobox gene MSX1, paired domain transcription
      factor PAX9, and EDA are associated with non-syndromic oligodontia. This study
      reports a Japanese family (eight of 14 family members affected) with non
      syndromic oligodontia who preferentially lacked molar teeth. In this family, a
      novel frameshift mutation (321_322insG) was identified in the paired domain of
      PAX9. The frameshift mutation caused altered amino acids in the paired domain and
      premature termination of translation by 26 amino acids. When transfected into COS
      7 cells, the mRNA expression of 321_322insG PAX9 was comparable with that of wild
      type PAX9. However, the mRNA of 321_322insG PAX9 was more unstable than that of
      wild-type PAX9. This mRNA instability caused a marked decrease in protein
      production, as evaluated by Western blot analysis and immunostaining. These
      findings suggest that the 321_322insG mutation causes insufficient function of
      PAX9 protein and haploinsufficiency as a genetic model of familial non-syndromic
      oligodontia with a PAX9 mutation.

PMID- 21098476
TI  - Randomized study of surgical prophylaxis in immunocompromised hosts.
AB  - Although prophylaxis is current practice, there are no randomized controlled
      studies evaluating preoperative antimicrobial prophylaxis in dental procedures in
      patients immunocompromised by chemotherapy or organ transplants. To evaluate
      prophylaxis in dental-invasive procedures in patients with cancer or solid organ
      transplants, 414 patients were randomized to receive one oral 500-mg dose 2 hours
      before the procedure (1-dose group) or a 500-mg dose 2 hours before the procedure
      and an additional dose 8 hours later (2-dose group). Procedures were exodontia or
      periodontal scaling/root planing. Follow-up was 4 weeks. No deaths or surgical
      site infections occurred. Six patients (1.4%) presented with use of pain
      medication > 3 days or hospitalization during follow-up: 4 of 207 (2%) in the 1
      dose group and 2 of 207 (1%) in the 2-dose group (relative risk, 2.02; 95%
      confidence interval, 0.37-11.15). In conclusion, no statistically significant
      difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for
      invasive dental procedures in immunocompromised patients.

PMID- 21098477
TI  - A Dbf4 mutant contributes to bypassing the Rad53-mediated block of origins of
      replication in response to genotoxic stress.
AB  - An intra-S phase checkpoint slows the rate of DNA replication in response to DNA
      damage and replication fork blocks in eukaryotic cells. In the budding yeast
      Saccharomyces cerevisiae, such down-regulation is achieved through the Rad53
      kinase-dependent block of origins of replication. We have identified the Rad53
      phosphorylation sites on Dbf4, the activator subunit of the essential S phase
      Dbf4-dependent kinase, and generated a non-phosphorylatable Dbf4 mutant
      (dbf4(7A)). We show here that dbf4(7A) is a bona fide intra-S phase checkpoint
      bypass allele that contributes to abrogating the Rad53 block of origin firing in
      response to genotoxic stress.

PMID- 21098478
TI  - RNA polymerase 1-driven transcription as a mediator of BDNF-induced neurite
      outgrowth.
AB  - Neurite outgrowth is essential for development of the nervous system.
      Neurotrophins including BDNF are among extracellular signals that regulate
      neurite outgrowth. The ERK1/2 pathway contributes to intracellular signaling
      networks transducing the pro-neuritic effects of BDNF. In the nucleolus, RNA
      polymerase-1 (Pol1)-mediated transcription regulates ribosomal biogenesis,
      enabling cellular protein synthesis and growth. Hence, we tested the possibility
      that Pol1 is an effector for pro-neuritic signals such as BDNF. We report that
      Pol1-mediated nucleolar transcription was increased by BDNF in an ERK1/2
      dependent manner in rat forebrain neurons. Conversely, in cultured hippocampal
      neurons, knockdown of a Pol1 coactivator, transcription initiation factor 1A
      (TIF1A), attenuated BDNF- or ERK1/2-induced neurite outgrowth. Also, upon
      overexpression, a constitutively active mutant of TIF1A strongly promoted neurite
      outgrowth, including increases in total neurite length and branching. Finally,
      overexpression of wild-type TIF1A enhanced the pro-neuritic effects of ERK1/2
      activation. These observations indicate that the Pol1-mediated nucleolar
      transcription regulates neurite outgrowth and serves as a major pro-neuritic
      effector of the BDNF-activated ERK1/2 pathway. Thus, development of the nervous
      system appears critically dependent on the nucleolus.

PMID- 21098479
TI  - A glutamine residue conserved in the neurotransmitter:sodium:symporters is
      essential for the interaction of chloride with the GABA transporter GAT-1.
AB  - Neurotransmitter:sodium symporters are crucial for efficient synaptic
      transmission. The transporter GAT-1 mediates electrogenic cotransport of GABA,
      sodium, and chloride. The presence of chloride enables the transporter to couple
      the transport of the neurotransmitter to multiple sodium ions, thereby enabling
      its accumulation against steep concentration gradients. Here we study the
      functional impact of mutations of the putative chloride-binding residues on
      transport by GAT-1, with the emphasis on a conserved glutamine residue. In
      contrast to another putative chloride coordinating residue, Ser-331, where
      mutation to glutamate led to chloride-independent GABA transport, the Q291E
      mutant was devoid of any transport activity, despite substantial expression at
      the plasma membrane. Low but significant transport activity was observed with
      substitution mutants with small side chains such as Q291S/A/G. Remarkably, when
      these mutations were combined with the S331E mutation, transport was increased
      significantly, even though the activity of the S331E single mutant was only ~25%
      of that of wild type GAT-1. Transport by these double mutants was largely
      chloride-independent. Like mutants of other putative chloride coordinating
      residues, the apparent affinity of the active Gln-291 single mutants for chloride
      was markedly reduced along with a change their anion selectivity. In addition to
      the interaction of the transporter with chloride, Gln-291 is also required at an
      additional step during transport. Electrophysiological analysis of the Q291N and
      Q291S mutants, expressed in Xenopus laevis oocytes, is consistent with the idea
      that this additional step is associated with the gating of the transporter.

PMID- 21098480
TI  - Malaria IMC1 membrane skeleton proteins operate autonomously and participate in
      motility independently of cell shape.
AB  - Plasmodium IMC1 (inner membrane complex 1) proteins comprise components of the
      subpellicular network, a lattice of intermediate filaments that form a structural
      part of the pellicle in the zoite stages of malaria parasites. Family members
      IMC1a and IMC1b are differentially expressed in sporozoites and ookinetes,
      respectively, but have functionally equivalent roles affecting cell morphology,
      strength, motility, and infectivity. Because of the coincident effects of
      previous imc1 gene disruptions on both zoite shape and locomotion, it has been
      impossible to ascribe a direct involvement in motility to these proteins. We show
      here that a third family member, IMC1h, has a distinct differential expression
      pattern and localizes to the pellicle of both ookinetes and sporozoites. Knock
      out of IMC1h mimics the loss-of-function phenotypes of IMC1a and IMC1b in their
      respective life stages, indicating that IMC1 proteins could be operating co
      dependently. By generating double null mutant parasites for IMC1h and IMC1b, we
      tested this hypothesis: double knock-out exacerbated the phenotypes of the single
      knock-outs in terms of ookinete strength, motility, and infectivity but did not
      further affect ookinete morphology. These findings provide the first genetic
      evidence that IMC1 proteins can function independently of each other and
      contribute to gliding motility independently of cell shape.

PMID- 21098481
TI  - Biochemical characterization of Pumilio1 and Pumilio2 in Xenopus oocytes.
AB  - Precise control of the timing of translational activation of dormant mRNAs stored
      in oocytes is required for normal progression of oocyte maturation. We previously
      showed that Pumilio1 (Pum1) is specifically involved in the translational control
      of cyclin B1 mRNA during Xenopus oocyte maturation, in cooperation with
      cytoplasmic polyadenylation element-binding protein (CPEB). It was reported that
      another Pumilio, Pumilio2 (Pum2), exists in Xenopus oocytes and that this protein
      regulates the translation of RINGO mRNA, together with Deleted in Azoospermia
      like protein (DAZL). In this study, we characterized Pum1 and Pum2 biochemically
      by using newly produced antibodies that discriminate between them. Pum1 and Pum2
      are bound to several key proteins involved in translational control of dormant
      mRNAs, including CPEB and DAZL, in immature oocytes. However, Pum1 and Pum2
      themselves have no physical interaction. Injection of anti-Pum1 or anti-Pum2
      antibody accelerated CPEB phosphorylation, cyclin B1 translation, and oocyte
      maturation. Pum1 phosphorylation coincides with the dissociation of CPEB from
      Pum1 and the translational activation of cyclin B1 mRNA, a target of Pum1,
      whereas Pum2 phosphorylation occurred at timing earlier than that for Pum1. Some,
      but not all, of cyclin B1 mRNAs release the deadenylase PARN during oocyte
      maturation, whereas Pum1 remains associated with the mRNA. On the basis of these
      findings, we discuss the functions of Pum1 and Pum2 in translational control of
      mRNAs during oocyte maturation.

PMID- 21098482
TI  - Stents, statins, and other dumb luck.

PMID- 21098483
TI  - Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against
      internalized Trypanosoma cruzi: consequences for oxidative killing and role of
      microbial peroxiredoxins in infectivity.
AB  - Macrophage-derived radicals generated by the NADPH oxidase complex and inducible
      nitric-oxide synthase (iNOS) participate in cytotoxic mechanisms against
      microorganisms. Nitric oxide ((*)NO) plays a central role in the control of acute
      infection by Trypanosoma cruzi, the causative agent of Chagas disease, and we
      have proposed that much of its action relies on macrophage-derived peroxynitrite
      (ONOO(-) + ONOOH) formation, a strong oxidant arising from the reaction of (*)NO
      with superoxide radical (O(2)(-)). Herein, we have shown that internalization of
      T. cruzi trypomastigotes by macrophages triggers the assembly of the NADPH
      oxidase complex to yield O(2)(-) during a 60-90-min period. This does not
      interfere with IFN-gamma-dependent iNOS induction and a sustained (*)NO
      production (~24 h). The major mechanism for infection control via reactive
      species formation occurred when (*)NO and O(2)() were produced simultaneously,
      generating intraphagosomal peroxynitrite levels compatible with microbial
      killing. Moreover, biochemical and ultrastructural analysis confirmed cellular
      oxidative damage and morphological disruption in internalized parasites.
      Overexpression of cytosolic tryparedoxin peroxidase in T. cruzi neutralized
      macrophage-derived peroxynitrite-dependent cytotoxicity to parasites and favored
      the infection in an animal model. Collectively, the data provide, for the first
      time, direct support for the action of peroxynitrite as an intraphagosomal
      cytotoxin against pathogens and the premise that microbial peroxiredoxins
      facilitate infectivity via decomposition of macrophage-derived peroxynitrite.

PMID- 21098484
TI  - The ubiquitin ligase MYCBP2 regulates transient receptor potential vanilloid
      receptor 1 (TRPV1) internalization through inhibition of p38 MAPK signaling.
AB  - The E3 ubiquitin ligase MYCBP2 negatively regulates neuronal growth,
      synaptogenesis, and synaptic strength. More recently it was shown that MYCBP2 is
      also involved in receptor and ion channel internalization. We found that mice
      with a MYCBP2-deficiency in peripheral sensory neurons show prolonged thermal
      hyperalgesia. Loss of MYCBP2 constitutively activated p38 MAPK and increased
      expression of several proteins involved in receptor trafficking. Surprisingly,
      loss of MYCBP2 inhibited internalization of transient receptor potential
      vanilloid receptor 1 (TRPV1) and prevented desensitization of capsaicin-induced
      calcium increases. Lack of desensitization, TRPV internalization and prolonged
      hyperalgesia were reversed by inhibition of p38 MAPK. The effects were TRPV
      specific, since neither mustard oil-induced desensitization nor behavioral
      responses to mechanical stimuli were affected. In summary, we show here for the
      first time that p38 MAPK activation can inhibit activity-induced ion channel
      internalization and that MYCBP2 regulates internalization of TRPV1 in peripheral
      sensory neurons as well as duration of thermal hyperalgesia through p38 MAPK.

PMID- 21098485
TI  - In vitro selection and characterization of HIV-1 variants with increased
      resistance to sifuvirtide, a novel HIV-1 fusion inhibitor.
AB  - Sifuvirtide, a novel fusion inhibitor against human immunodeficiency virus type I
      (HIV-1), which is more potent than enfuvirtide (T20) in cell culture, is
      currently under clinical investigation for the treatment of HIV-1 infection. We
      now report that in vitro selection of HIV-1 variants resistant to sifuvirtide in
      the presence of increasing concentrations of sifuvirtide has led to several
      specific mutations in the gp41 region that had not been previously reported. Many
      of these substitutions were confined to the N-terminal heptad repeat region at
      positions 37, 38, 41, and 43, either singly or in combination. A downstream
      substitution at position 126 (N126K) in the C-terminal heptad repeat region was
      also found. Site-directed mutagenesis studies have further identified the
      critical amino acid substitutions and combinations thereof in conferring the
      resistant genotypes. Furthermore, the mutant viruses demonstrated variable
      degrees of cross-resistance to enfuvirtide, some of which are preferentially more
      resistant to sifuvirtide. Impaired infectivity was also found for many of the
      mutant viruses. Biophysical and structural analyses of the key substitutions have
      revealed several potential novel mechanisms against sifuvirtide. Our results may
      help to predict potential resistant patterns in vivo and facilitate the further
      clinical development and therapeutic utility of sifuvirtide.

PMID- 21098486
TI  - Aromatic small molecules remodel toxic soluble oligomers of amyloid beta through
      three independent pathways.
AB  - In protein conformational disorders ranging from Alzheimer to Parkinson disease,
      proteins of unrelated sequence misfold into a similar array of aggregated
      conformers ranging from small oligomers to large amyloid fibrils. Substantial
      evidence suggests that small, prefibrillar oligomers are the most toxic species,
      yet to what extent they can be selectively targeted and remodeled into non-toxic
      conformers using small molecules is poorly understood. We have evaluated the
      conformational specificity and remodeling pathways of a diverse panel of aromatic
      small molecules against mature soluble oligomers of the Abeta42 peptide
      associated with Alzheimer disease. We find that small molecule antagonists can be
      grouped into three classes, which we herein define as Class I, II, and III
      molecules, based on the distinct pathways they utilize to remodel soluble
      oligomers into multiple conformers with reduced toxicity. Class I molecules
      remodel soluble oligomers into large, off-pathway aggregates that are non-toxic.
      Moreover, Class IA molecules also remodel amyloid fibrils into the same off
      pathway structures, whereas Class IB molecules fail to remodel fibrils but
      accelerate aggregation of freshly disaggregated Abeta. In contrast, a Class II
      molecule converts soluble Abeta oligomers into fibrils, but is inactive against
      disaggregated and fibrillar Abeta. Class III molecules disassemble soluble
      oligomers (as well as fibrils) into low molecular weight species that are non
      toxic. Strikingly, Abeta non-toxic oligomers (which are morphologically
      indistinguishable from toxic soluble oligomers) are significantly more resistant
      to being remodeled than Abeta soluble oligomers or amyloid fibrils. Our findings
      reveal that relatively subtle differences in small molecule structure encipher
      surprisingly large differences in the pathways they employ to remodel Abeta
      soluble oligomers and related aggregated conformers.

PMID- 21098487
TI  - Caveolin-1 assembles type 1 inositol 1,4,5-trisphosphate receptors and canonical
      transient receptor potential 3 channels into a functional signaling complex in
      arterial smooth muscle cells.
AB  - Physical coupling of sarcoplasmic reticulum (SR) type 1 inositol 1,4,5
      trisphosphate receptors (IP(3)R1) to plasma membrane canonical transient receptor
      potential 3 (TRPC3) channels activates a cation current (I(Cat)) in arterial
      smooth muscle cells that induces vasoconstriction. However, structural components
      that enable IP(3)R1 and TRPC3 channels to communicate locally are unclear.
      Caveolae are plasma membrane microdomains that can compartmentalize proteins.
      Here, we tested the hypothesis that caveolae and specifically caveolin-1 (cav-1),
      a caveolae scaffolding protein, facilitate functional IP(3)R1 to TRPC3 coupling
      in smooth muscle cells of resistance-size cerebral arteries. Methyl-beta
      cyclodextrin (MbetaCD), which disassembles caveolae, reduced IP(3)-induced I(Cat)
      activation in smooth muscle cells and vasoconstriction in pressurized arteries.
      Cholesterol replenishment reversed these effects. Cav-1 knockdown using shRNA
      attenuated IP(3)-induced vasoconstriction, but did not alter TRPC3 and IP(3)R1
      expression. A synthetic peptide corresponding to the cav-1 scaffolding domain
      (CSD) sequence (amino acids 82-101) also attenuated IP(3)-induced I(Cat)
      activation and vasoconstriction. A cav-1 antibody co-immunoprecipitated cav-1,
      TRPC3, and IP(3)R1 from cerebral artery lysate. ImmunoFRET indicated that cav-1,
      TRPC3 channels and IP(3)R1 are spatially co-localized in arterial smooth muscle
      cells. IP(3)R1 and TRPC3 channel spatial localization was disrupted by MbetaCD
      and a CSD peptide. Cholesterol replenishment re-established IP(3)R1 and TRPC3
      channel close spatial proximity. Taken together, these data indicate that in
      arterial smooth muscle cells, cav-1 co-localizes SR IP(3)R1 and plasma membrane
      TRPC3 channels in close spatial proximity thereby enabling IP(3)-induced physical
      coupling of these proteins, leading to I(Cat) generation and vasoconstriction.

PMID- 21098488
TI  - Geometric restraint drives on- and off-pathway catalysis by the Escherichia coli
      menaquinol:fumarate reductase.
AB  - Complex II superfamily members catalyze the kinetically difficult interconversion
      of succinate and fumarate. Due to the relative simplicity of complex II
      substrates and their similarity to other biologically abundant small molecules,
      substrate specificity presents a challenge in this system. In order to identify
      determinants for on-pathway catalysis, off-pathway catalysis, and enzyme
      inhibition, crystal structures of Escherichia coli menaquinol:fumarate reductase
      (QFR), a complex II superfamily member, were determined bound to the substrate,
      fumarate, and the inhibitors oxaloacetate, glutarate, and 3-nitropropionate.
      Optical difference spectroscopy and computational modeling support a model where
      QFR twists the dicarboxylate, activating it for catalysis. Orientation of the C2
      C3 double bond of activated fumarate parallel to the C(4a)-N5 bond of FAD allows
      orbital overlap between the substrate and the cofactor, priming the substrate for
      nucleophilic attack. Off-pathway catalysis, such as the conversion of malate to
      oxaloacetate or the activation of the toxin 3-nitropropionate may occur when
      inhibitors bind with a similarly activated bond in the same position. Conversely,
      inhibitors that do not orient an activatable bond in this manner, such as
      glutarate and citrate, are excluded from catalysis and act as inhibitors of
      substrate binding. These results support a model where electronic interactions
      via geometric constraint and orbital steering underlie catalysis by QFR.

PMID- 21098490
TI  - RNA 3'-phosphate cyclase (RtcA) catalyzes ligase-like adenylylation of DNA and
      RNA 5'-monophosphate ends.
AB  - RNA 3'-phosphate cyclase (Rtc) enzymes are a widely distributed family that
      catalyze the synthesis of RNA 2',3'-cyclic phosphate ends via an ATP-dependent
      pathway comprising three nucleotidyl transfer steps: reaction of Rtc with ATP to
      form a covalent Rtc-(histidinyl-N)-AMP intermediate and release PP(i); transfer
      of AMP from Rtc to an RNA 3'-phosphate to form an RNA(3')pp(5')A intermediate;
      and attack by the terminal nucleoside O2' on the 3'-phosphate to form an RNA
      2',3'-cyclic phosphate product and release AMP. The chemical transformations of
      the cyclase pathway resemble those of RNA and DNA ligases, with the key
      distinction being that ligases covalently adenylylate 5'-phosphate ends en route
      to phosphodiester synthesis. Here we show that the catalytic repertoire of RNA
      cyclase overlaps that of ligases. We report that Escherichia coli RtcA catalyzes
      adenylylation of 5'-phosphate ends of DNA or RNA strands to form AppDNA and
      AppRNA products. The polynucleotide 5' modification reaction requires the
      His(309) nucleophile, signifying that it proceeds through a covalent RtcA-AMP
      intermediate. We established this point directly by demonstrating transfer of
      [(32)P]AMP from RtcA to a pDNA strand. RtcA readily adenylylated the 5'-phosphate
      at a 5'-PO(4)/3'-OH nick in duplex DNA but was unable to covert the nicked DNA
      adenylate to a sealed phosphodiester. Our findings raise the prospect that
      cyclization of RNA 3'-ends might not be the only biochemical pathway in which Rtc
      enzymes participate; we discuss scenarios in which the 5'-adenylyltransferase of
      RtcA might play a role.

PMID- 21098491
TI  - Reducing inequality with improved oral research worldwide.

PMID- 21098489
TI  - De novo lipogenesis maintains vascular homeostasis through endothelial nitric
      oxide synthase (eNOS) palmitoylation.
AB  - Endothelial dysfunction leads to lethal vascular complications in diabetes and
      related metabolic disorders. Here, we demonstrate that de novo lipogenesis, an
      insulin-dependent process driven by the multifunctional enzyme fatty-acid
      synthase (FAS), maintains endothelial function by targeting endothelial nitric
      oxide synthase (eNOS) to the plasma membrane. In mice with endothelial
      inactivation of FAS (FASTie mice), eNOS membrane content and activity were
      decreased. eNOS and FAS were physically associated; eNOS palmitoylation was
      decreased in FAS-deficient cells, and incorporation of labeled carbon into eNOS
      associated palmitate was FAS-dependent. FASTie mice manifested a proinflammatory
      state reflected as increases in vascular permeability, endothelial inflammatory
      markers, leukocyte migration, and susceptibility to LPS-induced death that was
      reversed with an NO donor. FAS-deficient endothelial cells showed deficient
      migratory capacity, and angiogenesis was decreased in FASTie mice subjected to
      hindlimb ischemia. Insulin induced FAS in endothelial cells freshly isolated from
      humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or
      insulin-resistant diabetes. Thus, disrupting eNOS bioavailability through
      impaired lipogenesis identifies a novel mechanism coordinating nutritional status
      and tissue repair that may contribute to diabetic vascular disease.

PMID- 21098492
TI  - 'Young' oral fibroblasts are geno/phenotypically distinct.
AB  - Wound healing within the oral mucosa results in minimal scar formation compared
      with wounds within the skin. We have recently demonstrated distinct differences
      in the aging profiles of cells (oral mucosal and patient-matched skin
      fibroblasts) isolated from these tissues. We hypothesized that the increased
      replicative potential of oral mucosal fibroblasts may confer upon them
      preferential wound-healing capacities. Passage-matched early cultures of oral
      mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression
      profiles, with several genes linked to wound healing/tissue repair. This was
      related to an increased ability of the 'replicatively younger' oral mucosal
      fibroblasts to repopulate a wound space and reorganize their surrounding
      extracellular matrix environment, key activities during the wound-healing
      process. We conclude that oral mucosal fibroblasts exhibit a preferential healing
      response in vivo, due to their 'replicatively younger' phenotype when compared
      with that of patient-matched skin fibroblasts.

PMID- 21098493
TI  - Commentary.

PMID- 21098494
TI  - Laparoendoscopic single-site (LESS) nephroureterectomy and en bloc resection of
      bladder cuff with a novel extravesical endoloop technique.
AB  - OBJECTIVE: To present the initial experience of laparoendoscopic single-site
      (LESS) nephroureterectomy via the transperitoneal approach using the Alexis wound
      retractor and bladder cuff resection by endoloop. METHODS: Two patients received
      LESS nephroureterectomies and bladder cuffs resection with homemade single ports,
      which were created by using an Alexis wound retractor as an access platform
      through a 4-cm incision. Distal ureters were resected through the same incision
      with endoloop. No additional ports were used and both procedures were completed
      successfully. RESULTS: Both LESS procedures were completed successfully without
      traditional laparoscopic conversion or complication. LESS nephreoureterectomy
      with bladder cuff excision was performed in 165 and 325 minutes with estimated
      blood loss of 30 and 65 mL, respectively. Patients were discharged on
      postoperative days 3 and 7, respectively. CONCLUSIONS: The initial results
      demonstrated that LESS technique of nephroureterectomy and bladder cuff resection
      with endoloop is a safe and feasible procedure for urothelial carcinoma of upper
      urinary tract.

PMID- 21098495
TI  - Long-term follow-up after endovascular aneurysm repair: is ultrasound alone
      enough?
AB  - In the last decade, endovascular aneurysm repair (EVAR) has become the preferred
      method for infrarenal abdominal aortic aneurysm repair in patients with suitable
      anatomy. EVAR offers the advantage of lower perioperative morbidity and mortality
      but carries the cost of device-related complications such as endoleak, graft
      migration, graft thrombosis, and structural graft failure. These complications
      mandate a lifelong surveillance of EVAR patients and their endografts. Since the
      advent of EVAR, this has largely been accomplished with serial computed
      tomography (CT). There is, however, increasing awareness of the risks and costs
      of a lifelong CT imaging mandate, which has led to several cohort analyses
      comparing CT with color duplex ultrasonography (CDU) with contrast-enhanced
      ultrasound (CEUS) for the evaluation of the endograft and aneurysm sac post-EVAR.
      This review will summarize the findings of these reports and highlight the
      results of recent ultrasound-based surveillance strategies.

PMID- 21098496
TI  - Catheter-directed thrombectomy and thrombolysis for symptomatic lower-extremity
      deep vein thrombosis: review of current interventional treatment strategies.
AB  - Deep vein thromboses (DVT) along with its clinical sequelae represent a major
      health care challenge in our society. An acute massive DVT can result in
      pulmonary embolism resulting in sudden death. Although oral or systemic
      anticoagulation therapy may minimize thrombus propagation, it remains ineffective
      in removing thrombus burden and consequently does not prevent postthrombotic
      syndrome. Recent advances in catheter-based interventions have led to the
      development of a variety of minimally invasive endovascular strategies to remove
      venous thrombi. These technologies use various principles, including catheter
      directed thrombolytic infusion, rheolytic thrombectomy, mechanical fragmentation,
      or ultrasound energy to remove intraluminal thrombi. This article reviews the
      current advances in this technology and discusses the techniques of percutaneous
      treatment strategies of venous thrombotic conditions using various devices,
      including the AngioJet Power Pulse system, Trellis, and ultrasound-accelerated
      EkoSonic system. Finally, the authors' institutional experiences using these
      interventional treatment strategies in patients with acute and chronic DVT are
      discussed.

PMID- 21098497
TI  - Improved hemodynamic outcomes with glycopyrrolate over atropine in carotid
      angioplasty and stenting.
AB  - OBJECTIVE: Prophylactic atropine traditionally has been used to prevent CAS
      associated hemodynamic depression. Glycopyrrolate may serve as an alternative
      with decreased cardiac effects. This study aims to compare the efficacy of
      prophylactic glycopyrrolate to atropine in preventing CAS-induced hemodynamic
      instability and cardiac complications. METHODS: 115 consecutive CAS patients from
      2004-2010 were evaluated. Primary endpoints were stroke, MI, bradycardia (HR<60
      beats/min), and hypotension (systolic BP <90 mm Hg). Additional outcomes included
      tachycardia (HR >100 beats/min), hypertension (systolic BP >160 mm Hg), pre- and
      postoperative systolic BP difference, vasopressor use, arrhythmias, cardiac
      enzyme elevations, and access site complications. RESULTS: Of 115 patients, 65
      (56.5%) patients who received atropine or glycopyrrolate prior to CAS were
      analyzed [40 (61.5%) patients received glycopyrrolate, 25 (38.5%) received
      atropine]. Mean age was 70.0 +/- 8.5 years (range, 48-86 years). Mean stenosis
      was 86.2 +/- 7.4% (range, 70-99%). No MI, major stroke, or death was observed in
      the 30-day postoperative period. Baseline systolic BP and HR were equivalent
      between groups. Postoperative bradycardia and hypotension were significantly
      lower in glycopyrrolate patients compared with atropine patients (30% vs 72%, P =
      .002; 2.5% vs 36%, P < .001, respectively). Postoperative hypertension was also
      significantly lower in the glycopyrrolate cohort (2.5% vs 16%, P = .047), whereas
      tachycardia, pressure changes, vasopressor use, and cardiac complications did not
      differ significantly. No significant differences in neurologic and access site
      complications were observed. CONCLUSIONS: Prophylactic glycopyrrolate, compared
      with atropine, reduces hemodynamic instability during CAS. The authors recommend
      glycopyrrolate use to prevent CAS-induced bradycardia and hypotension.

PMID- 21098498
TI  - Endovascular interventions for acute pulmonary embolism.
AB  - Massive pulmonary embolism (PE) is a highly lethal condition with clinical
      manifestations of hemodynamic instability, acute right ventricular (RV) failure,
      and cardiogenic shock. Submassive PE, as defined by RV failure or troponin
      elevation, can result in life-threatening sequelae if treatment is not initiated
      promptly. Current treatment paradigm in patients with massive PE mandates prompt
      risk stratification with aggressive therapeutic strategies. With the advent of
      endovascular technologies, various catheter-based thrombectomy and thrombolytic
      devices are available to treat patients with massive or submassive PE. In this
      article, a variety of endovascular treatment strategies for PE are analyzed. The
      authors' institutional experience with ultrasound-accelerated thrombolytic
      therapy as well as catheter-directed thrombolytic therapy in patients with acute
      massive PE during a recent 10-year period is discussed. Finally, clinical
      evidence on the utilization of catheter-based interventions in patients with
      massive and submassive PE is also analyzed.

PMID- 21098499
TI  - Technique of reversed flared iliac stent graft for iliac aneurysms with
      discrepant size diameters.
AB  - PURPOSE: Endovascular treatment of iliac artery aneurysms (IAAs) in patients with
      discrepancy in iliac artery diameters can be challenging because of limited
      availability of reversed flared stent graft limbs. The authors describe the
      technique of reversing a Cook Zenith (Bloomington, IN) iliac stent graft
      extension to accommodate for significant discrepancy in diameter between the
      common iliac artery (18 mm) and the external iliac artery (11 mm). TECHNIQUE: A
      75-year-old male patient with a 7.3-cm right internal IAA was treated with
      endovascular exclusion of distal internal iliac artery branches using Amplatzer
      plugs (AGA Medical Corp, Plymouth, MN) and coverage of the internal iliac artery
      origin using a reversed 12 * 20 mm Cook Zenith TLFE Iliac extension limb
      (Bloomington, IN). The 12 * 20 mm iliac extension limb was unsheathed on-site
      using a strict sterile technique, reversed within the introducer and resheathed.
      Following percutaneous bilateral femoral access and exclusion of the anterior and
      posterior divisional branches of the internal iliac artery, the reversed flared
      iliac limb device was deployed from the distal common to the external iliac
      artery. Completion angiography and follow-up computed tomography angiography
      revealed no endoleak. The patient was dismissed on postoperative day 1 without
      complications. CONCLUSION: The technique of reversed flared iliac stent graft
      limb is a feasible option in patients with iliac aneurysms and significant
      discrepancy in the diameter of the iliac arteries.

PMID- 21098500
TI  - Carotid artery stenting using proximal balloon occlusion embolic protection.
AB  - Carotid artery stenting has rapidly grown as an alternative to carotid
      endarterectomy for stroke prevention among selected patients with extracranial
      carotid artery stenosis. Development of mechanical embolic protection devices
      (EPDs) has been associated with improved clinical outcomes and is now a strongly
      advocated adjunct to the procedure. Characteristically, EPDs have been broadly
      defined into 3 primary categories, of which the distal filter elements have
      largely been the most developed and used. Improvements among the class of
      proximal balloon occlusion devices with flow reversal have a number of theoretic
      advantages and are the focus of this review article.

PMID- 21098501
TI  - New technique to heal venous ulcers: terminal interruption of the reflux source
      (TIRS).
AB  - BACKGROUND: Treatment of healing venous ulcers continues to be a challenge;
      currently used techniques, as adjuncts to compression therapy aid to prevent
      recurrence but fail to heal ulcers. METHOD: A technique of terminal interruption
      of the reflux source (TIRS) was used. The TIRS procedure targets the terminal
      source of reflux. The purpose of the procedure is to temporarily reduce the
      venous hypertension at the local level, thus allowing healing to occur. By
      ultrasound guidance, 1% Sotradecol foam is injected into a venous branch or
      branches in close proximity to the ulcer bed. The branch may course under the
      ulcer or lead directly to it. Although more than one outflow source may be
      localized, all targeted veins must have documentation of reflux and have
      continuity with the primary source. RESULTS: To date, 14 patients have been
      treated. All had long-standing ulcers, 6 months to 2 years, and had been
      compliant with compression therapy. All patients were CEAP (clinical, etiologic,
      anatomic, pathophysiologic) class 6 with a venous clinical severity score ranging
      from 12 to 22. Rapid healing of all venous ulcers with an average time to ulcer
      healing of 6 to 8 weeks has been achieved. In all, 7 patients are ulcer free at 5
      years, 4 patients are ulcer free for more than 2 years, 2 patients are ulcer free
      at 1 year, and 1 patient is undergoing treatment on remaining ulcers. CONCLUSION:
      TIRS is a safe and effective treatment to heal venous ulcers. Local reduction of
      venous hypertension is the underlying factor for promoting rapid healing. More
      studies and careful documentation will likely prove the validity of this
      treatment regime.

PMID- 21098505
TI  - Collagen-related genes influence the glaucoma risk factor, central corneal
      thickness.
AB  - Central corneal thickness (CCT) is a risk factor of glaucoma, the most common
      cause of irreversible blindness worldwide. The identification of genetic
      determinants affecting CCT in the normal population will provide insights into
      the mechanisms underlying the association between CCT and glaucoma, as well as
      the pathogenesis of glaucoma itself. We conducted two genome-wide association
      studies for CCT in 5080 individuals drawn from two ethnic populations in
      Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci
      significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 * 10-13,
      interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 * 10-9). We confirmed the
      involvement of a previously reported gene for CCT and brittle cornea syndrome
      (ZNF469) [rs9938149 (p(meta) = 1.63 * 10-16) and rs12447690 (p(meta) = 1.92 * 10
      14)]. Evidence of association exceeding the formal threshold for genome-wide
      significance was observed at rs7044529, an SNP located within COL5A1 when data
      from this study (n = 5080, P = 0.0012) were considered together with all
      published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 * 10
      9). These findings implicate the involvement of collagen genes influencing CCT
      and thus, possibly the pathogenesis of glaucoma.

PMID- 21098503
TI  - Alcohol affects the late differentiation of progenitor B cells.
AB  - AIMS: Previous studies show that alcohol exposure can affect the differentiation
      of progenitor B cells. Before final commitment to a B lineage, progenitor B cells
      usually undergo several important stages. However, it is still unclear whether
      alcohol alters B cell differentiation at which stages. The aim of this study was
      to determine which stage(s) of progenitor cell differentiation are affected by
      alcohol and to elucidate the mechanism(s) responsible for the effect of alcohol
      on B cell differentiation. METHODS: Oligoclonal-neonatal-progenitor (ONP) cells
      from bone marrow cells of 2-week-old mice were cultured under different
      conditions in vitro with or without the exposure of 100 mM alcohol. Phenotype
      analysis was performed at different time points and expression levels of
      transcription factors (TFs) and cytokine receptors were measured quantitatively
      and kinetically. RESULTS: After 3 days in vitro culture, ONP cells differentiated
      into two populations: B220(-)CD11b(-) and B220(-)CD11b(+) cells. B220(-)CD11b(-)
      cells can further differentiate into B lineage cells only with the support of
      B220(-)CD11b(+) cells. Cells exposed to 100 mM of alcohol during the first 3 days
      of culture showed no statistically significant difference in B cell formation
      after 12 days compared with the control group. However, cells exposed to alcohol
      from Day 4 till the end of culture yield very few B cells. Expression levels of
      TFs and cytokine receptors were down-regulated kinetically among ONP cells co
      cultured with the addition of 100 mM alcohol. CONCLUSIONS: Alcohol affects the
      ONP cell differentiation into B lineage at a late stage. Alcohol also down
      regulates the expression level of TFs and cytokine receptors resulting in the
      impairment of B cell differentiation.

PMID- 21098506
TI  - Impaired minor tri-snRNP assembly generates differential splicing defects of U12
      type introns in lymphoblasts derived from a type I SMA patient.
AB  - The survival of motor neuron (SMN) protein is essential for cytoplasmic assembly
      of spliceosomal snRNPs. Although the normal proportion of endogenous snRNAs is
      unevenly altered in spinal muscular atrophy (SMA) tissues, the biogenesis of
      individual snRNPs is not dramatically affected in SMN-deficient cells. The SMN
      protein is also required for normal Cajal body (CB) formation, but the functional
      consequences of CB disruption upon SMN deficiency have not yet been analyzed at
      the level of macromolecular snRNPs assembly. Here, we show that the SMN protein
      is required for tri-snRNPs formation and that the level of the minor
      U4atac/U6atac/U5 tri-snRNPs is dramatically decreased in lymphoblasts derived
      from a patient suffering from a severe form of SMA. We found also that splicing
      of some, but not all, minor introns is inhibited in these cells, demonstrating
      links between SMN deficiency and differential alterations of splicing events
      mediated by the minor spliceosome. Our results suggest that SMA might result from
      the inefficient splicing of one or only a few pre-mRNAs carrying minor introns
      and coding for proteins required for motor neurons function and/or organization.

PMID- 21098508
TI  - Postoperative permanent pacemaker implantation in patients undergoing trans
      catheter aortic valve implantation: what is the incidence and are there any
      predicting factors?
AB  - A best evidence topic was written according to a structured protocol. The issue
      was to determine the incidence and predictors of postoperative permanent
      pacemaker (PPM) implantation in patients undergoing trans-catheter aortic valve
      implantation (TAVI) for symptomatic calcific aortic stenosis and to compare this
      to the known risks of this complication following surgical aortic valve
      replacement (AVR). Using the reported search method 3071 articles were
      identified, of which 94 were relevant to the procedure of TAVI and 14 were deemed
      to represent the best evidence. All 14 studies, including both multi-centre
      registries and single-centre retrospective case series containing >=30 patients,
      reported incidence of postoperative PPM implantation. Five of these studies also
      assessed predictors of the need for postoperative PPM implantation. The author,
      journal, date and country of publication, study type, level of evidence, patient
      group, outcomes and results were tabulated for these studies. We conclude that
      the current best available evidence suggests that the mean incidence of PPM
      implantation following TAVI is 14.2% (range 0-34%, median 9.7%), although this
      appears higher with the CoreValve prosthesis (five studies, mean 20.8%, range 9.3
      30.0%) than with the Edwards-Sapien prosthesis (six studies, mean 5.4%, range 0
      10.1%). The mean incidences of PPM implantation overall and when using the
      CoreValve prosthesis are higher than the mean incidence of 7.0% (range 3-11.8%,
      median 7.2%) following conventional AVR and may be explained by distinct
      differences between the patient groups involved and the procedure performed.
      Indications for PPM implantation appear to occur early in the postoperative
      period following TAVI and there is little evidence of recovery following
      atrioventricular block (AVB). New onset persistent left bundle branch block is
      common following TAVI but the significance and follow-up required is unclear.
      Independent predictors of PPM requirement following TAVI include use of the
      CoreValve prosthesis and evidence of conduction system dysfunction, either pre
      existing right bundle branch block or AVB at the time of TAVI. All patients
      should be made aware of the high risk of PPM implantation with TAVI.

PMID- 21098507
TI  - Phenylbutyrate therapy for maple syrup urine disease.
AB  - Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate in urea cycle
      disorder patients has been associated with a selective reduction in branched
      chain amino acids (BCAA) in spite of adequate dietary protein intake. Based on
      this clinical observation, we investigated the potential of phenylbutyrate
      treatment to lower BCAA and their corresponding alpha-keto acids (BCKA) in
      patients with classic and variant late-onset forms of maple syrup urine disease
      (MSUD). We also performed in vitro and in vivo experiments to elucidate the
      mechanism for this effect. We found that BCAA and BCKA are both significantly
      reduced following phenylbutyrate therapy in control subjects and in patients with
      late-onset, intermediate MSUD. In vitro treatment with phenylbutyrate of control
      fibroblasts and lymphoblasts resulted in an increase in the residual enzyme
      activity, while treatment of MSUD cells resulted in the variable response which
      did not simply predict the biochemical response in the patients. In vivo
      phenylbutyrate increases the proportion of active hepatic enzyme and
      unphosphorylated form over the inactive phosphorylated form of the E1alpha
      subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC).
      Using recombinant enzymes, we show that phenylbutyrate prevents phosphorylation
      of E1alpha by inhibition of the BCKDC kinase to activate BCKDC overall activity,
      providing a molecular explanation for the effect of phenylbutyrate in a subset of
      MSUD patients. Phenylbutyrate treatment may be a valuable treatment for reducing
      the plasma levels of neurotoxic BCAA and their corresponding BCKA in a subset of
      MSUD patients and studies of its long-term efficacy are indicated.

PMID- 21098509
TI  - Diagnostic accuracy of multidetector spiral computed tomography for preoperative
      assessment of sinus venosus atrial septal defects in children.
AB  - OBJECTIVES: To prospectively assess the value of multidetector computed
      tomography (MDCT) for detecting partial anomalous pulmonary venous return (PAPVR)
      in children with suspected sinus venosus-atrial septal defect (SV-ASD). METHODS:
      Forty-four children (mean age, 7.3 years; range, nine months-16 years) from whom
      transthoracic echocardiography (TTE) was inconclusive for the diagnosis underwent
      MDCT after contrast medium injection. Diagnosis was suspected on TTE by abnormal
      pulmonary venous return, no visualization of pulmonary venous ostia, or
      unexpected dilatation of right cavities. The first 11 children also underwent
      cardiac catheterization. Surgical findings constituted the diagnostic reference
      standard. RESULTS: Thirty-two (73%) children had SV-ASD with PAPVR. Of the first
      11 patients, one had PAPVR by MDCT and 10 by conventional angiography; these 11
      patients had PAPVR by surgery. Of the remaining 33 patients, 21 had SV-ASD and 12
      had ostium secundum ASD, by both MDCT and surgery. MDCT had 100% sensitivity,
      100% specificity, 100% positive predictive value, and 100% negative predictive
      value for diagnosing PAPVR in patients with suspected SV-ASD. CONCLUSION:
      Contrast-enhanced MDCT is a highly accurate, minimally-invasive technique for
      detecting PAPVR associated with SV-ASD. Contrast-enhanced MDCT may be used safely
      to replace conventional angiography for the definitive diagnosis and preoperative
      evaluation of children with suspected SV-ASD.

PMID- 21098510
TI  - The role of ascorbic acid in the prevention of atrial fibrillation after elective
      on-pump myocardial revascularization surgery: a single-center experience--a pilot
      study.
AB  - Atrial fibrillation (AF) is a common arrhythmia that occurs postoperatively in
      cardiac surgery. There is evidence for the role of oxidative stress in the
      etiology of AF. In our study, we examined whether antioxidant ascorbic acid
      (vitamin C), could help in the reduction of the incidence of postoperative AF.
      Patients who were scheduled to undergo elective isolated on-pump coronary artery
      bypass grafting (CABG) were included in our study. One hundred and seventy
      patients were randomly divided in two groups: Group A (n=85) received vitamin C
      preoperatively and postoperatively whereas Group B (n=85) did not receive any
      (control group). The incidence of AF was 44.7% in the vitamin C group and 61.2%
      in the control group (P=0.041). The hospitalization time, the intensive care unit
      stay and the time interval for the conversion of AF into sinus rhythm was
      significantly shorter in the vitamin C group. Patients that developed AF also had
      longer hospital length of stay (9.5+/-2.8 days vs. 6.7+/-1.9, P=0.034).
      Supplementation of vitamin C reduces the incidence of postCABG AF, and decreases
      the time needed for rhythm restoration and length of hospital stay.

PMID- 21098511
TI  - Engineering bioartificial tracheal tissue using hybrid fibroblast-mesenchymal
      stem cell cultures in collagen hydrogels.
AB  - We aimed at providing the first in vitro and in vivo proof-of-concept for a novel
      tracheal tissue engineering technology. We hypothesized that bioartificial
      trachea (BT) could be generated from fibroblast and collagen hydrogels,
      mechanically supported by osteogenically-induced mesenchymal stem cells (MSC) in
      ring-shaped 3D-hydrogel cultures, and applied in an experimental model of rat
      trachea injury. Tube-shaped tissue was constructed from mixtures of rat
      fibroblasts and collagen in custom-made casting molds. The tissue was
      characterized histologically and mechanically. Ring-shaped tissue was constructed
      from mixtures of rat MSCs and collagen and fused to the tissue-engineered tubes
      to function as reinforcement. Stiffness of the biological reinforcement was
      enhanced by induction of osteogeneic differentiation in MSCs. Osteogenic
      differentiation was evaluated by assessment of osteocalcin (OC) secretion,
      quantification of calcium (Ca) deposit, and mechanical testing. Finally, BT was
      implanted to bridge a surgically-induced tracheal defect. A three-layer tubular
      tissue structure composed of an interconnected network of fibroblasts was
      constructed. Tissue collapse was prevented by the placement of MSC-containing
      ring-shaped tissue reinforcement around the tubular constructs. Osteogenic
      induction resulted in high OC secretion, high Ca deposit, and enhanced construct
      stiffness. Ultimately, when BT was implanted, recipient rats were able to breathe
      spontaneously.

PMID- 21098512
TI  - Modification of the Cabrol as a bailout procedure in complicated bicuspid valve
      aortopathy.
AB  - The Cabrol technique is reserved where the conventional 'button' or Bentall
      techniques fail to maintain a tension-free anastomosis between the coronary
      arteries and aortic conduit. However, the side-to-side anastomosis of the
      interposition graft that connects the coronary ostia with the aorta in the
      Cabrol, may lead to kinking or tension, and subsequent occlusion. We present a
      case of successful Cabrol modification in a patient with bicuspid aortopathy
      where the graft to the right coronary artery was anastomosed directly onto the
      valved conduit and the graft to the left main stem onto the previous right
      aortocoronary graft in a T-fashion.

PMID- 21098513
TI  - Trapping and characterization of covalent intermediates of mutant retaining
      glycosyltransferases.
AB  - The enzymatic mechanism by which retaining glycosyltransferases (GTs) transfer
      monosaccharides with net retention of the anomeric configuration has, so far,
      resisted elucidation. Here, direct detection of covalent glycosyl-enzyme
      intermediates for mutants of two model retaining GTs, the human blood group
      synthesizing alpha-(1 -> 3)-N-acetylgalactosaminyltransferase (GTA) and alpha-(1 
      > 3)-galactosyltransferase (GTB) mutants, by mass spectrometry (MS) is reported.
      Incubation of mutants of GTA or GTB, in which the putative catalytic nucleophile
      Glu(303) was replaced with Cys (i.e. GTA(E303C) and GTB(E303C)), with their
      respective donor substrate results in a covalent intermediate. Tandem MS analysis
      using collision-induced dissociation confirmed Cys(303) as the site of
      glycosylation. Exposure of the glycosyl-enzyme intermediates to a disaccharide
      acceptor results in the formation of the corresponding enzymatic trisaccharide
      products. These findings suggest that the GTA(E303C) and GTB(E303C) mutants may
      operate by a double-displacement mechanism.

PMID- 21098514
TI  - Desulfovibrio desulfuricans PglB homolog possesses oligosaccharyltransferase
      activity with relaxed glycan specificity and distinct protein acceptor sequence
      requirements.
AB  - Oligosaccharyltransferases (OTases) are responsible for the transfer of
      carbohydrates from lipid carriers to acceptor proteins and are present in all
      domains of life. In bacteria, the most studied member of this family is PglB from
      Campylobacter jejuni (PglB(Cj)). This enzyme is functional in Escherichia coli
      and, contrary to its eukaryotic counterparts, has the ability to transfer a
      variety of oligo- and polysaccharides to protein carriers in vivo. Phylogenetic
      analysis revealed that in the delta proteobacteria Desulfovibrio sp., the PglB
      homolog is more closely related to eukaryotic and archaeal OTases than to its
      Campylobacter counterparts. Genetic analysis revealed the presence of a putative
      operon that might encode all enzymes required for N-glycosylation in
      Desulfovibrio desulfuricans. D. desulfuricans PglB (PglB(Dd)) was cloned and
      successfully expressed in E. coli, and its activity was confirmed by transferring
      the C. jejuni heptasaccharide onto the model protein acceptor AcrA. In contrast
      to PglB(Cj), which adds two glycan chains to AcrA, a single oligosaccharide was
      attached to the protein by PglB(Dd). Site-directed mutagenesis of the five
      putative N-X-S/T glycosylation sites in AcrA and mass spectrometry analysis
      showed that PglB(Dd) does not recognize the "conventional bacterial glycosylation
      sequon" consisting of the sequence D/E-X(1)-N-X(2)-S/T (where X(1) and X(2) are
      any amino acid except proline), and instead used a different site for the
      attachment of the oligosaccharide than PglB(Cj.). Furthermore, PglB(Dd) exhibited
      relaxed glycan specificity, being able to transfer mono- and polysaccharides to
      AcrA. Our analysis constitutes the first characterization of an OTase from delta
      proteobacteria involved in N-linked protein glycosylation.

PMID- 21098515
TI  - Elucidation of exo-beta-D-glucosaminidase activity of a family 9 glycoside
      hydrolase (PBPRA0520) from Photobacterium profundum SS9.
AB  - A glycoside hydrolase (GH) gene from Photobacterium profundum SS9 (PBPRA0520)
      belonging to GH family 9 was expressed in Escherichia coli. The protein was
      expressed with the intact N-terminal sequence, suggesting that it is an
      intracellular enzyme. The recombinant protein showed hydrolytic activity toward
      chitobiose [(GlcN)(2)] and cellobiose (CG(2)) in various disaccharides. This
      protein also released 4-nitrophenol (PNP) from both 4-nitrophenyl-beta-D
      glucosaminide (GlcN-PNP) and 4-nitrophenyl-beta-D-glucoside (Glc-PNP). The
      hydrolytic pattern observed in chitooligosaccharides and cellooligosaccharides
      suggested that the reaction proceeded from the nonreducing end in an exo-type
      manner. Time-dependent (1)H-nuclear magnetic resonance (NMR) analysis of the
      anomeric form of the enzymatic reaction products indicated that the protein is an
      inverting enzyme. k(cat)/K(m) of (GlcN)(2) hydrolysis was 14 times greater than
      that of CG(2) hydrolysis. These results suggested that the protein is an exo-beta
      D-glucosaminidase (EC 3.2.1.165) rather than a glucan 1,4-beta-D-glucosidase (EC
      3.2.1.74). Based on the results, we suggest that the function of conserved GH9
      proteins in the chitin catabolic operon is to cleave a (GlcN)(2)-phosphate
      derivative by hydrolysis during intracellular chitooligosaccharide catabolism in
      Vibrionaceae.

PMID- 21098516
TI  - Structural analysis of alpha1,3-linked galactose-containing oligosaccharides in
      Schizosaccharomyces pombe mutants harboring single and multiple alpha
      galactosyltransferase genes disruptions.
AB  - In the fission yeast Schizosaccharomyces pombe, galactose (Gal) residues are
      transferred to N- and O-linked oligosaccharides of glycoproteins by
      galactosyltransferases in the lumen of the Golgi apparatus. In S. pombe, the
      major in vitro alpha1,2-galactosyltransferase activity has been purified, the
      gma12(+) gene has been cloned, and three alpha-galactosyltransferase genes
      (gmh1(+)-gmh3(+)) have also been partially characterized. In this study, we found
      three additional uncharacterized genes with homology to gmh1(+) (gmh4(+)-gmh6(+))
      in the fission yeast genome sequence. All possible single disruption mutants and
      the septuple disruption strain were constructed and characterized. The
      electrophoretic mobility of acid phosphatase prepared from gma12Delta, gmh2Delta,
      gmh3Delta and gmh6Delta mutants was higher than that from wild type, indicating
      that Gma12p, Gmh2p, Gmh3p and Gmh6p are required for the galactosylation of N
      linked oligosaccharides. High-performance liquid chromatography (HPLC) analysis
      of pyridylaminated O-linked oligosaccharides from each single mutant showed that
      Gma12p, Gmh2p and Gmh6p are involved in galactosylation of O-linked
      oligosaccharides. The septuple mutant exhibited similar drug and temperature
      sensitivity as a gms1Delta mutant that is incapable of galactosylation.
      Oligosaccharide structural analysis based on HPLC and methylation analysis
      revealed that the septuple mutant still contained oligosaccharides consisting of
      alpha1,3-linked Gal residues, indicating that an unknown alpha1,3
      galactosyltransferase activity was still present in the septuple mutant.

PMID- 21098517
TI  - Conservation of the ST6Gal I gene and its expression in the mammary gland.
AB  - Milk sialoglycoconjugates can protect the gastrointestinal tract of the suckling
      neonate by competitively binding to invading pathogens and promoting growth of
      beneficial flora, and their potential role in postnatal brain development is of
      particular interest in human infant nutrition. Although the concentration and the
      distribution of sialoglycoconjugates have been extensively studied in the milk of
      various species, the investigation of sialyltransferase gene expression in the
      mammary gland, in the context of lactation, has been limited. The
      sialyltransferase enzyme ST6Gal I transfers sialic acid from CMP-sialic acid to
      type 2 (Galbeta1,4GlcNAc) free disaccharides or the termini of N- or O-linked
      oligosaccharides using an alpha2,6-linkage. Expression of the ST6Gal I gene is
      primarily regulated at the level of transcription through the use of several cell
      and development-specific promoters, producing transcripts with divergent 5'
      untranslated regions (UTR). In the mouse mammary gland, the novel 5'UTR exon (L)
      appears to be associated with a drastic increase in ST6Gal I gene expression
      during lactation. We find that rats also possess an exon (L), suggesting
      conservation of this regulatory mechanism in rodents. In contrast, an exon (L)
      containing transcript was not detected in the lactating bovine or human mammary
      gland. We also observed a trend of increasing ST6Gal I gene expression in the
      bovine mammary gland, culminating in involution. This is in contrast to species
      such as mice where the greatest change in ST6Gal I gene expression occurs between
      pregnancy and lactation, suggesting different roles in rodents vs. other mammals
      for alpha2,6-sialylated oligosaccharides present in milk.

PMID- 21098518
TI  - Current trends in the structure-activity relationships of sialyltransferases.
AB  - Sialyltransferases (STs) represent an important group of enzymes that transfer N
      acetylneuraminic acid (Neu5Ac) from cytidine monophosphate-Neu5Ac to various
      acceptor substrates. In higher animals, sialylated oligosaccharide structures
      play crucial roles in many biological processes but also in diseases, notably in
      microbial infection and cancer. Cell surface sialic acids have also been found in
      a few microorganisms, mainly pathogenic bacteria, and their presence is often
      associated with virulence. STs are distributed into five different families in
      the CAZy database (http://www.cazy.org/). On the basis of crystallographic data
      available for three ST families and fold recognition analysis for the two other
      families, STs can be grouped into two structural superfamilies that represent
      variations of the canonical glycosyltransferase (GT-A and GT-B) folds. These two
      superfamilies differ in the nature of their active site residues, notably the
      catalytic base (a histidine or an aspartate residue). The observed structural and
      functional differences strongly suggest that these two structural superfamilies
      have evolved independently.

PMID- 21098519
TI  - Parental preferences for FDA-approved medications prescribed for their children.
AB  - OBJECTIVE: To describe parental preferences for FDA-approved prescription
      medications for their children. STUDY DESIGN: Cross-sectional Web-enabled survey
      of a national sample of 1562 parents. RESULTS: Response rate was 61%. Most
      parents (77%) preferred prescription of only FDA-approved medications for their
      child. However, one half of parents preferred that their child's doctor prescribe
      medication that is safest and works best, even if not FDA approved for children.
      One third of parents (34%) preferred nothing but FDA-approved medications for
      their child, regardless of drug safety, effectiveness, or cost. Controlling for
      parent race and education, mothers (odds ratio = 1.52; P = .004) and older
      parents (odds ratio = 1.60; P = .025) were more likely to prefer nothing but FDA
      approved medications for their children compared with fathers and younger
      parents. CONCLUSIONS: Although most parents initially indicate preference for FDA
      approved medications, one half of parents will accept a non-FDA-approved
      medication for their children with the understanding that it is safer or more
      effective than the FDA-approved alternative.

PMID- 21098520
TI  - Pain management in young children undergoing diagnostic tympanocentesis.
AB  - OBJECTIVE: To describe the pain associated with diagnostic tympanocentesis and to
      gather preliminary data comparing the efficacy of 3 methods of pain reduction for
      tympanocentesis. METHODS: In children 6 to 36 months of age undergoing
      tympanocentesis for acute otitis media, the authors measured pain and distress
      throughout all phases of the procedure and recovery using physiological (heart
      rate) and behavioral measures (cry duration, Global Mood Scale score, and pain
      visual analog scales). They compared--in a randomized controlled trial--3 pain
      reduction interventions: acetaminophen, acetaminophen plus codeine, and ibuprofen
      plus midazolam. RESULTS: Heart rate increased throughout the procedure, peaking
      during needle aspiration. Children treated with acetaminophen alone had higher
      peak heart rates and Global Mood Scale scores during parts of the procedure.
      CONCLUSIONS: Acetaminophen alone may not be as effective in reducing pain-related
      physiological and behavioral changes as acetaminophen plus codeine or ibuprofen
      plus midazolam during diagnostic tympanocentesis.

PMID- 21098521
TI  - Comparison of the Inverness Medical Acceava Strep A test with the Genzyme OSOM
      and Quidel QuickVue Strep A tests.
AB  - Previous studies of the accuracy of rapid in-office tests for group A
      Streptococcus had disparate results, ranging from a sensitivity of 70% to more
      than 90%. The sensitivity and specificity of 3 commercially available Strep A
      tests were determined in 2 private pediatric office settings. Acceava Strep A,
      Genzyme OSOM Strep A, and the Quidel QuickVue Strep A tests were the
      representative rapid tests for detection of Streptococcus pyogenes. Overnight
      culture on standard 5% sheep blood agar was the reference standard for this
      study. All 3 Clinical Laboratory Improvement Amendments-waived tests had
      sensitivities and specificities that exceeded 95%.

PMID- 21098522
TI  - The impact of linezolid and vancomycin treatment on local signs and symptoms of
      inflammation among pediatric patients with complicated skin and skin structure
      infections.

PMID- 21098523
TI  - An office-based low-carbohydrate intervention in teens: one-year follow-up of a
      six-month intervention.

PMID- 21098524
TI  - 5-4-3-2-1 go! Coordinating pediatric resident education and community health
      promotion to address the obesity epidemic in children and youth.
AB  - This study investigated the feasibility and effectiveness of training pediatric
      residents to conduct a brief clinic-based behavioral intervention in coordination
      with community dissemination of a health promotion message developed by the
      Consortium for Lowering Obesity in Chicago Children. A total of 113 residents
      completed a short (<60 minutes) online training program. Some (64) residents
      distributed interview contact cards to patients they saw in their continuity of
      care clinics after training; others (45) distributed cards before training. A
      researcher interviewed 75% of the 509 patients 4 weeks after the visit. More
      patients of trained residents reported positive changes in behaviors which have
      been associated with lower obesity rates: increased intake of fruits and
      vegetables (28% vs 16%, P < .01), increased intake of water (30% vs 19%, P <
      .01), increased physical activity (40% vs 29%, P < .03), and decreased television
      time (36% vs 24%, P < .01). Brief training using the 5-4-3-2-1-Go! message seems
      to be feasible and effective.

PMID- 21098525
TI  - Tree nut allergy, egg allergy, and asthma in children.
AB  - BACKGROUND: Children with food allergies often have concurrent asthma. OBJECTIVE:
      The authors aimed to determine the prevalence of asthma in children with food
      allergies and the association of specific food allergies with asthma. METHODS:
      Parental questionnaire data regarding food allergy, corroborated by allergic
      sensitization were completed for a cohort of 799 children with food allergies.
      Multivariate regression analysis tested the association between food allergy and
      reported asthma. RESULTS: In this cohort, the prevalence of asthma was 45.6%.
      After adjusting for each food allergy, environmental allergies, and family
      history of asthma, children with egg allergy (odds ratio [OR] = 2.0; 95%
      confidence interval [CI] = 1.3-3.2; P < .01) or tree nut allergy (OR = 2.0; 95%
      CI = 1.1-3.6; P = .02) had significantly greater odds of report of asthma.
      CONCLUSION: There is a high prevalence of asthma in the food-allergic pediatric
      population. Egg and tree nut allergy are significantly associated with asthma,
      independent of other risk factors.

PMID- 21098526
TI  - Pneumococcal resistance and serotype 19A in Pittsburgh-area children with acute
      otitis media before and after introduction of 7-valent pneumococcal
      polysaccharide vaccine.
AB  - METHODS: Before and after introduction of pneumococcal conjugate vaccine (PCV7),
      the authors obtained nasopharyngeal (NP) specimens from 3 groups of children aged
      6 to 23 months with acute otitis media (AOM): group 1 (pre-PCV7), group 2 (early
      post-PCV7), and group 3 (late post-PCV7). RESULTS: Of the Streptococcus
      pneumoniae isolates, the proportion that were vaccine serotypes (VTs) declined
      progressively (60.4% vs 48.6% vs 5.2% in groups 1, 2, and 3, respectively; P <
      .001). Concurrently, increases occurred in the proportion of penicillin
      nonsusceptible isolates (minimum inhibitory concentration >0.1 ug/mL; 26.7% vs
      37.8% vs. 38.5%; P = .12); the proportion of isolates that were serotype 19A
      (4.0% vs 0% vs 25.9%; P < .001); and the proportion of 19A isolates that were
      penicillin-nonsusceptible (0% in group 1, 68.6% in group 3; P = .004).
      CONCLUSION: Shifts in pneumococcal serotype distribution and increases in
      penicillin nonsusceptibility among pneumococcal isolates from children with AOM
      underscore the need for continuing bacteriological surveillance for future
      vaccine development.

PMID- 21098527
TI  - Perception and attitude of providers toward pain and anxiety associated with
      pediatric vaccine injection.
AB  - Despite the many options available for control of the pain and anxiety during
      vaccine injections, they are not often used. A total of 70 primary care providers
      (PCPs) were asked to rate their perception of pain and anxiety associated with
      vaccine injection in an average 4- to 6-year-old using a visual analog scale-0
      (no pain/anxiety) to 10 (very severe pain/anxiety)-as well as perceived barriers.
      The mean PCPs' perception of pain associated with vaccine injection was 5.7 (95%
      confidence interval [CI] = 5.3-6.1), and perceived anxiety was 7.7 (95% CI = 7.2
      8.1). Trainees recorded higher perceived anxiety than attending physicians (8.0
      vs 6.9; P = .03)]. Of the respondents, 63 (90%) felt that pain and anxiety
      control is achievable in their office setting. Nevertheless, only 8 (11%) PCPs
      had ordered any pain and anxiety control measures during vaccine injection. There
      is a gap between the PCPs' perception of pain and anxiety and practice of pain
      and anxiety control measures during vaccine injection.

PMID- 21098528
TI  - Parental perceptions of sleep disturbances and sleep-disordered breathing in
      children with Down syndrome.
AB  - OBJECTIVES: Children with Down syndrome (DS) have increased difficulty initiating
      and maintaining sleep (DIMS), excessive daytime sleepiness (EDS), and obstructive
      sleep apnea (OSA). As part of a quality improvement initiative, parents of
      children enrolled in the Children's Hospital Boston Down Syndrome Program were
      surveyed about their child's sleep and breathing patterns while asleep. METHODS:
      An anonymous Internet-based questionnaire was used in the study. RESULTS: The
      completion rate was 46.5% (255/548). DIMS and EDS were frequently/almost always
      present in more than half the children. Among parents unconcerned about their
      child's breathing, 11.8% witnessed apnea and 4.2% gasping/choking more than once
      monthly. Parents of children status post adenotonsillectomy (AT) reported
      witnessed apnea (47.5%), gasping/choking (28.9%) more than once monthly.
      DISCUSSION: There is room for improved screening of sleep disturbances, OSA in
      children with DS. The high frequency of persistence of OSA following AT should
      prompt for continued screening following AT.

PMID- 21098529
TI  - Thrombocytopenic syndromes masquerading as childhood immune thrombocytopenic
      purpura.
AB  - Immune thrombocytopenic purpura (ITP) is the most common cause of
      thrombocytopenia in children and adolescents. However, there are a number of
      other diagnoses that are often mistaken for ITP. A 10-year retrospective chart
      review was performed at the Children's Hospital of Alabama to characterize ITP.
      Initially, 492 patients who had the coded diagnosis of ITP (ICD 287.3) were
      identified. However, 83 (17%) of patients were found to have alternative
      diagnoses on chart review. Of the 83 patients, 13 patients (3%) represented
      coding errors or study classification errors. The 70 remaining patients (14%) had
      an alternative explanation for their thrombocytopenia, consisting of 31 different
      diagnoses. The most common diagnoses were familial thrombocytopenia (10%),
      systemic lupus erythematosus (9%), hypersplenism (9%), neonatal alloimmune
      thrombocytopenia (7%), Wiskott-Aldrich syndrome (7%), or systemic infection (6%).
      In total, 16 of the patients (23%) were ultimately diagnosed with one of a number
      of congenital syndromes with concurrent thrombocytopenia. Although this review
      confirms that most children with thrombocytopenia are diagnosed with ITP, 14% of
      the study population manifested other diagnoses. The clinician evaluating a child
      with thrombocytopenia must keep an open mind about the possible diagnosis and
      perform a comprehensive and thoughtful evaluation based on the clinical picture.
      ITP must be a diagnosis of exclusion as misdiagnosis in a child with
      thrombocytopenia may have a significant impact on morbidity and mortality.

PMID- 21098530
TI  - A child with Wegener's granulomatosis and severe hemophilia A: interplay of
      disease processes.

PMID- 21098531
TI  - Attention deficit/hyperactivity disorder in preschool-age children: issues and
      concerns.
AB  - The diagnosis of attention deficit/hyperactivity disorder (ADHD) in children has
      been steadily increasing over the past 10 years. ADHD is associated with numerous
      health, behavioral, social, and academic outcomes. The use of medication is
      common for the treatment of ADHD. However, the evidence base for pharmacological
      and non-pharmacological treatments for children younger than 6 years of age is
      limited. Both short-term and long-term studies of efficacy and safety of all
      interventions are needed in this population, especially the use of psychotropic
      medications. Understanding the long-term effects of psychotropic medication on
      the developing brains of preschoolers has important implications for outcomes
      into adulthood. Nonpharmacologic evidence-based interventions are available and
      should serve as the first line of treatment in this population. Future research
      needs include further evidence regarding specific curricula, dose, duration,
      delivery methods, and staff training to ensure optimal intervention outcomes.

PMID- 21098532
TI  - Completion of the 2-dose influenza vaccine series among children aged 6 to 59
      months: immunization information system sentinel sites, 2007-2008 influenza
      season.

PMID- 21098533
TI  - A case of Henoch-Schonlein purpura presenting with a gastrocutaneous fistula.

PMID- 21098534
TI  - The changing clinical presentation of hypertrophic pyloric stenosis: the
      experience of a large, tertiary care pediatric hospital.
AB  - The authors reviewed the clinical and laboratory data from cases of hypertrophic
      pyloric stenosis (HPS) diagnosed at their institution from 2006 to 2008. They
      assessed and compared presentation of patients with HPS over time at their
      institution. A total of 118 patients were included in this study. An "olive" was
      palpated in only 13.6% of cases. This is in contrast to older studies, where more
      than 50% of the patients were reported to have a palpable "olive" depending on
      when the study was conducted. In patients from this institution, hypochloremia
      was present in 23% and alkalosis in 14.4%, which are less frequent than the
      incidence of these abnormalities in older studies. There was a change in the
      additional "classical" symptoms, represented by the lower percentage of infants
      in whom an "olive" was palpated and the lower numbers of patients with severe
      electrolyte imbalances. The reason for this change appears to be the frequent use
      of ultrasound.

PMID- 21098535
TI  - Three sequential malignancies in a child.

PMID- 21098536
TI  - Differences in male and female adolescents from various racial groups in the
      relationship between insulin resistance-associated parameters with sugar
      sweetened beverage intake and physical activity levels.
AB  - OBJECTIVE: To describe racial and gender differences in insulin resistance
      associated parameters due to sugar-sweetened beverage (SSB) intake and physical
      activity (PA) levels in the adolescent population. METHODS: Data from individuals
      aged 12 to 19 years from the National Health and Nutrition Examination Survey
      during the years 1999-2004 were analyzed. SSB intake and PA levels were evaluated
      in Non-Hispanic whites, Non-Hispanic blacks, and Mexican Americans. Outcome
      measures included measurements of insulin sensitivity, lipids, blood pressure,
      waist circumference, and body mass index. RESULTS: Multivariate linear regression
      analyses showed that anthropometric measurements, metabolic parameters, and
      indices of insulin resistance differed among the racial groups. Moreover, within
      each of these racial groups, they differed between the sexes. CONCLUSIONS: The
      differing relationships between insulin resistance-associated parameters and SSB
      intake and PA levels among racial groups and between the sexes illustrate the
      importance of race and gender in the investigation of diseases such as obesity
      and metabolic syndrome.

PMID- 21098537
TI  - A baby with generalized edema.

PMID- 21098538
TI  - McCune Albright syndrome: epidermal nevus syndrome.

PMID- 21098539
TI  - NDM-1-producing Klebsiella pneumoniae isolated in the Sultanate of Oman.
AB  - OBJECTIVES: To analyse the mechanisms responsible for multidrug resistance in two
      carbapenem-resistant Klebsiella pneumoniae isolates recovered from patients
      hospitalized in Oman. METHODS: PCR and sequencing were used to search for beta
      lactamase and 16S RNA methylase genes. Multilocus sequence typing was used to
      determine the sequence type (ST) of each isolate. Clonal relationships were
      evaluated by PFGE. RESULTS: Both isolates carried the bla(NDM-1) carbapenemase
      gene. Isolate 601 was recovered from a patient who was transferred from India,
      whereas isolate 419 was from an Omani patient who had not travelled abroad. The
      two isolates were clonally unrelated, and belonged to ST14 (isolate 601) and
      ST340 (isolate 419). In addition to NDM-1, the ST14 isolate expressed beta
      lactamases CTX-M-15, SHV-28, OXA-1, OXA-9 and TEM-1, and the aminoglycoside
      resistance methylase ArmA. The ST340 isolate expressed beta-lactamases SHV-11,
      OXA-1 and ArmA. In both isolates, the bla(NDM-1) gene was located on plasmids
      that were of similar size (170 kb), but of different incompatibility groups.
      CONCLUSION: This is the first description of NDM-1 producers in the Arabian
      peninsula and in the Middle East.

PMID- 21098540
TI  - The role of Escherichia coli YrbB in the lethal action of quinolones.
AB  - OBJECTIVES: To explore bacterial cellular factors that protect against the lethal
      effect of antimicrobial stress as potential targets of antimicrobial
      potentiators, the role of Escherichia coli YrbB in protecting cells from
      quinolone-mediated cell death was studied. METHODS: A set of isogenic strains
      containing different mutations in stress response genes of E. coli was
      constructed by P1-mediated transduction. The susceptibility of these strains to
      the lethal action of quinolones was determined by measuring viable colony counts
      on agar plates after treatment with quinolones under various conditions. RESULTS:
      A yrbB mutation rendered E. coli cells more susceptible to the lethal action of
      quinolones under conditions in which bacteriostatic susceptibility was
      unaffected. YrbB worked in both lethal pathways of quinolone action. Hydroxyl
      radical accumulation was required for nalidixic acid-mediated killing; however,
      in the absence of functional YrbB there was an additional mechanism through which
      nalidixic acid could kill cells independently of hydroxyl radical action. The E.
      coli chromosomal toxin-antitoxin system ChpB, but not the SOS system, was found
      to be involved in the hydroxyl radical-independent lethal mechanism. In addition,
      proteases ClpP and Lon were also involved in the action of YrbB. Besides
      quinolones, YrbB also played a protective role in cellular responses to other
      stressors, such as mitomycin C, ultraviolet light and hydrogen peroxide.
      CONCLUSIONS: YrbB played a protective role in the lethal action of quinolones
      through a hydroxyl radical-independent and toxin-antitoxin-dependent mechanism,
      which makes it a potential target for antimicrobial enhancement.

PMID- 21098541
TI  - Efavirenz concentrations in CSF exceed IC50 for wild-type HIV.
AB  - OBJECTIVES: HIV-associated neurocognitive disorders remain common despite use of
      potent antiretroviral therapy (ART). Ongoing viral replication due to poor
      distribution of antivirals into the CNS may increase risk for HIV-associated
      neurocognitive disorders. This study's objective was to determine penetration of
      a commonly prescribed antiretroviral drug, efavirenz, into CSF. METHODS: CHARTER
      is an ongoing, North American, multicentre, observational study to determine the
      effects of ART on HIV-associated neurological disease. Single random plasma and
      CSF samples were drawn within 1 h of each other from subjects taking efavirenz
      between September 2003 and July 2007. Samples were assayed by HPLC or HPLC/mass
      spectrometry with detection limits of 39 ng/mL (plasma) and <0.1 ng/mL (CSF).
      RESULTS: Eighty participants (age 44 +/- 8 years; 79 +/- 15 kg; 20 females) had
      samples drawn 12.5 +/- 5.4 h post-dose. The median efavirenz concentrations after
      a median of 7 months [interquartile range (IQR) 2-17] of therapy were 2145 ng/mL
      in plasma (IQR 1384-4423) and 13.9 ng/mL in CSF (IQR 4.1-21.2). The CSF/plasma
      concentration ratio from paired samples drawn within 1 h of each other was 0.005
      (IQR 0.0026-0.0076; n = 69). The CSF/IC(50) ratio was 26 (IQR 8-41) using the
      published IC(50) for wild-type HIV (0.51 ng/mL). Two CSF samples had
      concentrations below the efavirenz IC(50) for wild-type HIV. CONCLUSIONS:
      Efavirenz concentrations in the CSF are only 0.5% of plasma concentrations but
      exceed the wild-type IC(50) in nearly all individuals. Since CSF drug
      concentrations reflect those in brain interstitial fluids, efavirenz reaches
      therapeutic concentrations in brain tissue.

PMID- 21098542
TI  - Prevalence of Escherichia coli carrying extended-spectrum beta-lactamases (CTX-M
      and TEM-52) from broiler chickens and turkeys in Great Britain between 2006 and
      2009.
AB  - OBJECTIVES: to determine the prevalence of extended-spectrum beta-lactamases
      (ESBLs) in Escherichia coli from poultry in Great Britain (GB). METHODS: E. coli
      was isolated from 388 broiler chicken caecal samples from 22 abattoirs and from
      boot swabs from 442 turkey flocks over successive 1 year periods. CHROMagar ECC
      with and without cephalosporin antibiotics was used as isolation medium and the
      chicken study also used CHROMagar CTX. ESBL phenotype isolates were tested for
      the presence of bla(CTX-M,) bla(OXA), bla(SHV), bla(TEM) and ampC genes(.) CTX-M
      isolates were tested for O25 serogroup, replicon, CTX-M sequence, multilocus
      sequence type (MLST), PFGE type, plasmid transfer and qnrA, qnrB, qnrS, qepA and
      aac(6')-Ib genes. RESULTS: CTX-M-carrying E. coli were isolated from 54.5% of the
      broiler abattoirs and from 3.6% of individual broiler caecal samples and were CTX
      M sequence types 1 (mainly), 3 and 15 with replicon types I1-gamma, A/C and P/F,
      and I1-gamma, respectively. CTX-M-carrying E. coli were isolated from 5.2% of
      turkey meat production farms and 6.9% of turkey breeder farms and were CTX-M
      sequence types 1, 14 (mainly), 15 and 55 with mainly replicon types F, FIA, K and
      I1-gamma, respectively. None of the CTX-M isolates was serogroup O25. PFGE/MLST
      showed the CTX-M isolates to be clonally diverse, although MLST 156 with CTX-M-15
      was isolated from both chickens and turkeys and has been previously reported in
      gulls. CTX-M-negative, ESBL- and bla(TEM)-positive strains were mainly TEM-52C.
      CONCLUSIONS: poultry-derived CTX-M E. coli in GB are different from major CTX-M
      sequence types causing disease in humans.

PMID- 21098544
TI  - Editorial.

PMID- 21098543
TI  - Mortality associated with in-hospital bacteraemia caused by Staphylococcus
      aureus: a multistate analysis with follow-up beyond hospital discharge.
AB  - OBJECTIVES: The main objective was to study the impact of in-hospital bacteraemia
      caused by Staphylococcus aureus on mortality within 90 days after admission. We
      compared methicillin-resistant S. aureus (MRSA) with methicillin-susceptible S.
      aureus (MSSA). PATIENTS AND METHODS: The study population consisted of adult
      residents of Tayside, Scotland, UK, from 1 January 2005 to 30 September 2006 who
      had a new admission to Ninewells Hospital between 1 July 2005 and 30 June 2006.
      All patients (n = 3132) in the same wards as the patients infected with S. aureus
      were included. We addressed key weaknesses in previous studies by using a cohort
      design and applying a multistate model, which addressed the temporal dynamics.
      Critically, the model recognized that death and discharge from the hospital are
      competing events and that delay in discharge independently increases the risk of
      death. RESULTS: The cohort included 3132 patients, of whom 494 died within 90
      days after admission, 34 developed MRSA bacteraemia and 26 MSSA bacteraemia in
      the hospital. In comparison with patients without S. aureus bacteraemia, the
      death hazard was 5.6 times greater with MRSA [95% confidence interval (CI) 3.36
      9.41] and 2.7 times greater with MSSA bacteraemia (95% CI 1.33-5.39). After
      adjustment for co-morbidity, hospitalization, age and sex, the death hazard was
      2.9 times greater with MRSA (95% CI 1.70-4.88) and 1.7 times greater with MSSA
      bacteraemia (95% CI 0.84-3.47). CONCLUSIONS: Time-dependent models such as the
      proposed multistate model are necessary to address the temporal dynamics of
      admission, infection, discharge and death. The impact of S. aureus bacteraemia on
      mortality should be considered on two levels: the burden of disease, i.e.
      nosocomial infection with S. aureus bacteraemia, and the burden of resistance to
      methicillin.

PMID- 21098546
TI  - Probabilistic Bayesian reasoning can help identifying potentially wrong
      immunoassays results in clinical practice: even when they appear 'not
      unreasonable'.
AB  - BACKGROUND: Immunoassays are susceptible to analytical interferences including
      from endogenous immunoglobulin antibodies at a rate of ~0.4% to 4%. Hundreds of
      millions of immunoassay tests (>10 millions in the UK alone) are performed yearly
      worldwide for measurements of an array of large and small moieties such as
      proteins, hormones, tumour markers, rheumatoid factor, troponin, small peptides,
      steroids and drugs. METHODS: Interference in these tests can lead to false
      results which when suspected, or surmised, can be analytically confirmed in most
      cases. Suspecting false laboratory data in the first place is not difficult when
      results are gross and without clinical correlates. However, when false results
      are subtle and/or plausible, it can be difficult to suspect with adverse clinical
      sequelae. This problem can be ameliorated by using a probabilistic Bayesian
      reasoning to flag up potentially suspect results even when laboratory data appear
      "not-unreasonable". RESULTS: Essentially, in disorders with low prevalence, the
      majority of positive results caused by analytical interference are likely to be
      false positives. On the other hand, when the disease prevalence is high, false
      negative results increase and become more significant. To illustrate the scope
      and utility of this approach, six different examples covering wide range of
      analytes are given, each highlighting specific aspect/nature of interference and
      suggested options to reduce it. CONCLUSION: Bayesian reasoning would allow
      laboratorians and/or clinicians to extract information about potentially false
      results, thus seeking follow-up confirmatory tests prior to the initiation of
      more expensive/invasive procedures or concluding a potentially wrong diagnosis.

PMID- 21098545
TI  - Particle size of apoB-48 carrying lipoproteins in remnant lipoproteins isolated
      from postprandial plasma.
AB  - BACKGROUND: Particle size of apoB-48 carrying lipoproteins in remnant-like
      lipoprotein particles (RLP) in postprandial plasma has not been well
      characterized. METHODS: Plasma lipids, lipoproteins and apolipoproteins in 12
      healthy subjects were analysed after an oral fat load. RLP isolated by
      immunoaffinity gel from plasma of a normolipidaemic and a hyperlipidaemic subject
      in four hours after an oral fat load was fractionated by high-performance liquid
      chromatography (HPLC) and monitored by total cholesterol (TC), triglycerides
      (TG), apoB-48 and apoB-100. RESULTS: TC, low-density lipoprotein (LDL)-C and apoB
      did not change after an oral fat load, while TG, RLP-C, RLP-TG and apoB-48
      increased significantly in postprandial plasma. HPLC profiles monitored by TC and
      TG revealed that major lipoproteins increased in RLP after an oral fat load was
      VLDL size particles. The percentage of RLP-TG in total TG and the ratio of RLP
      TG/RLP-C were significantly increased in four hours after an oral fat load
      compared with the fasting state (P < 0.01). RLP in four hours after an oral fat
      load fractionated by HPLC and monitored by TC, TG, apoB-48 and apoB-100 revealed
      that VLDL size or smaller particles were the major lipoproteins. CONCLUSIONS:
      ApoB-48 carrying lipoproteins in RLP isolated from a normolipidaemic and a
      hyperlipidaemic subject after an oral fat load showed a similar particle size
      with apoB-100 carrying VLDL remnants. Therefore, the most apoB-48 carrying
      particles found in postprandial RLP can be classified as CM remnants. The
      majority of remnants in the postprandial state were not CM remnants, but VLDL
      remnants.

PMID- 21098547
TI  - Central pontine myelinolysis in a patient with epilepsia partialis continua and
      hyperglycaemic hyperosmolar state.
AB  - Central pontine myelinolysis (CPM) is a demyelinating disorder, which is
      associated most commonly with the rapid correction of hyponatraemia and other
      abrupt changes in physiological osmotic conditions. This includes the treatment
      of hyperosmolar hyperglycaemia in diabetes mellitus (DM) sufferers. Herein, we
      report a case of CPM in a 55-y-old patient with new-onset DM who presented with
      partial focal seizures and a sudden-onset right-sided hemiplegia. Magnetic
      resonance imaging revealed a lesion in the central pons. The patient responded to
      glucose control and antiepileptic medication, and achieved a recovery of limb
      function within 17 d of admission. CPM occurred in this patient before the
      correction of hyperglycaemic hyperosmolar state, and a disturbance in his initial
      electrolytes was not found. This report is the first documented case of long-term
      hyperglycaemic hyperosmolar state leading to CPM, and highlights that CPM can
      present as an isolated hemiplegia.

PMID- 21098548
TI  - High-sensitivity troponin T as a marker of myocardial injury after radiofrequency
      catheter ablation.
AB  - BACKGROUND: The aim of our study was to monitor radiofrequency catheter ablation
      induced myocardial damage by measuring high-sensitivity cardiac troponin T (hs
      cTnT). METHODS: Serum concentrations of hs-cTnT (Elecsys 2010 system, Roche) were
      measured in 73 healthy blood donors and serially in 27 patients who had samples
      taken both before and 24 h after radiofrequency ablation (RFA) for
      atrioventricular nodal re-entry tachycardia (AVNRT), atrial fibrillation (AF) or
      right atrial flutter (AFL). RESULTS: Significant increases of hs-cTnT were seen
      in patients after RFA (AVNRT: P = 0.0115, AF: P = 0.0011, AFL: P = 0.0009).
      Postprocedural serum hs-cTnT correlated with the number of radiofrequency
      applications and with the duration of RFA procedure. Spearman's coefficient of
      rank correlation (r) were as follows: hs-cTnT versus RFA duration: r = 0.771 (P <
      0.001); hs-cTnT versus number of pulses: r = 0.708 (P < 0.001). Patients with the
      diagnosis of AVNRT had lower serum hs-cTnT concentration after RFA compared with
      AFL (P < 0.0001) and AF (P < 0.0001) patients. CONCLUSIONS: Our data indicate
      that RFA causes a significant increase of serum hs-cTnT concentration that could
      be used to monitor myocardial injury.

PMID- 21098549
TI  - Attentional bias in smokers: exposure to dynamic smoking cues in contemporary
      movies.
AB  - Research has shown that smokers have an attentional bias for pictorial smoking
      cues. The objective of the present study was to examine whether smokers also have
      an attentional bias for dynamic smoking cues in contemporary movies and therefore
      fixate more quickly, more often and for longer periods of time on dynamic smoking
      cues than non-smokers. By drawing upon established methods for assessing
      attentional biases for pictorial cues, we aimed to develop a new method for
      assessing attentional biases for dynamic smoking cues. We examined smokers' and
      non-smokers' eye movements while watching a movie clip by using eye-tracking
      technology. The sample consisted of 16 smoking and 17 non-smoking university
      students. Our results confirm the results of traditional pictorial attentional
      bias research. Smokers initially directed their gaze more quickly towards smoking
      related cues (p = 0.01), focusing on them more often (p = 0.05) and for a longer
      duration (p = 0.01) compared with non-smokers. Thus, smoking cues in movies
      directly affect the attention of smokers. These findings indicate that the
      effects of dynamic smoking cues, in addition to other environmental smoking cues,
      need to be taken into account in smoking cessation therapies in order to increase
      successful smoking cessation and to prevent relapses.

PMID- 21098551
TI  - Commentary on: Abiomed Impella((r)) 2.5 patient transport: lessons learned.

PMID- 21098552
TI  - The impact of different biocompatible coated cardiopulmonary bypass circuits on
      inflammatory response and oxidative stress.

PMID- 21098554
TI  - Acute malnutrition and under-5 mortality, northeastern part of India.
AB  - We assessed the prevalence of childhood acute malnutrition and under-five
      mortality rate (U5MR) in Darbhanga district, India, using a two-stage 49-cluster
      household survey. A total of 1379 households comprising 8473 people were
      interviewed. During a 90-day recall period, U5MR was 0.5 [95% confidence interval
      (CI), 0.2-1.4] per 10,000 per day. The prevalence of global acute malnutrition
      among 1405 children aged 6-59 months was 15.4% (NCHS) and 19.4% (2006 WHO
      references). This survey suggests that in Darbhanga district, the population is
      in a borderline food crisis with few food resources. Appropriate strategies
      should be developed to improve the overall nutritional and health status of
      children.

PMID- 21098555
TI  - Percutaneous double valve intervention.

PMID- 21098556
TI  - The outer chloroplast envelope protein OEP16-1 for plastid import of
      NADPH:protochlorophyllide oxidoreductase A in Arabidopsis thaliana.
AB  - The outer plastid envelope protein OEP16-1 was previously identified as an amino
      acid-selective channel protein and translocation pore for
      NADPH:protochlorophyllide oxidoreductase A (PORA). Reverse genetic approaches
      used to dissect these mutually not exclusive functions of OEP16-1 in planta have
      led to descriptions of different phenotypes resulting from the presence of
      several mutant lines in the SALK_024018 seed stock. In addition to the T-DNA
      insertion in the AtOEP16-1 gene, lines were purified that contain two additional
      T-DNA insertions and as yet unidentified point mutations. In a first attempt to
      resolve the genetic basis of four different lines in the SALK_024018 seed stock,
      we used genetic transformation with the OEP16-1 cDNA and segregation analyses
      after crossing out presumed point mutations. We show that AtOEP16-1 is involved
      in PORA precursor import and by virtue of this activity confers photoprotection
      onto etiolated seedlings during greening.

PMID- 21098557
TI  - Implication of the oep16-1 mutation in a flu-independent, singlet oxygen
      regulated cell death pathway in Arabidopsis thaliana.
AB  - Singlet oxygen is a prominent form of reactive oxygen species in higher plants.
      It is easily formed from molecular oxygen by triplet-triplet interchange with
      excited porphyrin species. Evidence has been obtained from studies on the flu
      mutant of Arabidopsis thaliana of a genetically determined cell death pathway
      that involves differential changes at the transcriptome level. Here we report on
      a different cell death pathway that can be deduced from the analysis of oep16
      mutants of A. thaliana. Pure lines of four independent OEP16-deficient mutants
      with different cell death properties were isolated. Two of the mutants
      overproduced free protochlorophyllide (Pchlide) in the dark because of defects in
      import of NADPH:Pchlide oxidoreductase A (pPORA) and died after illumination. The
      other two mutants avoided excess Pchlide accumulation. Using pulse labeling and
      polysome profiling studies we show that translation is a major site of cell death
      regulation in flu and oep16 plants. flu plants respond to photooxidative stress
      triggered by singlet oxygen by reprogramming their translation toward synthesis
      of key enzymes involved in jasmonic acid synthesis and stress proteins. In
      contrast, those oep16 mutants that were prone to photooxidative damage were
      unable to respond in this way. Together, our results show that translation is
      differentially affected in the flu and oep16 mutants in response to singlet
      oxygen.

PMID- 21098558
TI  - Cdx1 refines positional identity of the vertebrate hindbrain by directly
      repressing Mafb expression.
AB  - An interplay of transcription factors interprets signalling pathways to define
      anteroposterior positions along the vertebrate axis. In the hindbrain, these
      transcription factors prompt the position-appropriate appearance of seven to
      eight segmental structures, known as rhombomeres (r1-r8). The evolutionarily
      conserved Cdx caudal-type homeodomain transcription factors help specify the
      vertebrate trunk and tail but have not been shown to directly regulate hindbrain
      patterning genes. Mafb (Kreisler, Krml1, valentino), a basic domain leucine
      zipper transcription factor, is required for development of r5 and r6 and is the
      first gene to show restricted expression within these two segments. The
      homeodomain protein vHnf1 (Hnf1b) directly activates Mafb expression. vHnf1 and
      Mafb share an anterior expression limit at the r4/r5 boundary but vHnf1
      expression extends beyond the posterior limit of Mafb and, therefore, cannot
      establish the posterior Mafb expression boundary. Upon identifying regulatory
      sequences responsible for posterior Mafb repression, we have used in situ
      hybridization, immunofluorescence and chromatin immunoprecipitation (ChIP)
      analyses to determine that Cdx1 directly inhibits early Mafb expression in the
      neural tube posterior of the r6/r7 boundary, which is the anteriormost boundary
      of Cdx1 expression in the hindbrain. Cdx1 dependent repression of Mafb is
      transient. After the 10-somite stage, another mechanism acts to restrict Mafb
      expression in its normal r5 and r6 domain, even in the absence of Cdx1. Our
      findings identify Mafb as one of the earliest direct targets of Cdx1 and show
      that Cdx1 plays a direct role in early hindbrain patterning. Thus, just as Cdx2
      and Cdx4 govern the trunk-to-tail transition, Cdx1 may regulate the hindbrain-to
      spinal cord transition.

PMID- 21098559
TI  - The repression of Notch signaling occurs via the destabilization of mastermind
      like 1 by Mesp2 and is essential for somitogenesis.
AB  - The rostro-caudal polarity within a somite is primarily determined by the on/off
      state of Notch signaling, but the mechanism by which Notch is repressed has
      remained elusive. Here, we present genetic and biochemical evidence that the
      suppression of Notch signaling is essential for the establishment of rostro
      caudal polarity within a somite and that Mesp2 acts as a novel negative regulator
      of the Notch signaling pathway. We generated a knock-in mouse in which a dominant
      negative form of Rbpj is introduced into the Mesp2 locus. Intriguingly, this
      resulted in an almost complete rescue of the segmental defects in the Mesp2-null
      mouse. Furthermore, we demonstrate that Mesp2 potently represses Notch signaling
      by inducing the destabilization of mastermind-like 1, a core regulator of this
      pathway. Surprisingly, this function of Mesp2 is found to be independent of its
      function as a transcription factor. Together, these data demonstrate that Mesp2
      is a novel component involved in the suppression of Notch target genes.

PMID- 21098560
TI  - The Rho kinase Rock2b establishes anteroposterior asymmetry of the ciliated
      Kupffer's vesicle in zebrafish.
AB  - The vertebrate body plan features a consistent left-right (LR) asymmetry of
      internal organs. In several vertebrate embryos, motile cilia generate an
      asymmetric fluid flow that is necessary for normal LR development. However, the
      mechanisms involved in orienting LR asymmetric flow with previously established
      anteroposterior (AP) and dorsoventral (DV) axes remain poorly understood. In
      zebrafish, asymmetric flow is generated in Kupffer's vesicle (KV). The cellular
      architecture of KV is asymmetric along the AP axis, with more ciliated cells
      densely packed into the anterior region. Here, we identify a Rho kinase gene,
      rock2b, which is required for normal AP patterning of KV and subsequent LR
      development in the embryo. Antisense depletion of rock2b in the whole embryo or
      specifically in the KV cell lineage perturbed asymmetric gene expression in
      lateral plate mesoderm and disrupted organ LR asymmetries. Analyses of KV
      architecture demonstrated that rock2b knockdown altered the AP placement of
      ciliated cells without affecting cilia number or length. In control embryos,
      leftward flow across the anterior pole of KV was stronger than rightward flow at
      the posterior end, correlating with the normal AP asymmetric distribution of
      ciliated cells. By contrast, rock2b knockdown embryos with AP patterning defects
      in KV exhibited randomized flow direction and equal flow velocities in the
      anterior and posterior regions. Live imaging of Tg(dusp6:memGFP)(pt19) transgenic
      embryos that express GFP in KV cells revealed that rock2b regulates KV cell
      morphology. Our results suggest a link between AP patterning of the ciliated
      Kupffer's vesicle and LR patterning of the zebrafish embryo.

PMID- 21098562
TI  - An interview with Patrick Tam by Kathryn Senior.
AB  - Patrick Tam's research is focused on the cellular and molecular mechanisms of
      body patterning during mouse development. He agreed to be interviewed by
      Development to talk about his interest in mouse development, new concepts in
      gastrulation, X-linked diseases and his dream of an African safari.

PMID- 21098561
TI  - Geminin cooperates with Polycomb to restrain multi-lineage commitment in the
      early embryo.
AB  - Transient maintenance of a pluripotent embryonic cell population followed by the
      onset of multi-lineage commitment is a fundamental aspect of development.
      However, molecular regulation of this transition is not well characterized in
      vivo. Here, we demonstrate that the nuclear protein Geminin is required to
      restrain commitment and spatially restrict mesoderm, endoderm and non-neural
      ectoderm to their proper locations in the Xenopus embryo. We used microarray
      analyses to demonstrate that Geminin overexpression represses many genes
      associated with cell commitment and differentiation, while elevating expression
      levels of genes that maintain pluripotent early and immature neurectodermal cell
      states. We characterized the relationship of Geminin to cell signaling and found
      that Geminin broadly represses Activin-, FGF- and BMP-mediated cell commitment.
      Conversely, Geminin knockdown enhances commitment responses to growth factor
      signaling and causes ectopic mesodermal, endodermal and epidermal fate commitment
      in the embryo. We also characterized the functional relationship of Geminin with
      transcription factors that had similar activities and found that Geminin
      represses commitment independent of Oct 4 ortholog (Oct25/60) activities, but
      depends upon intact Polycomb repressor function. Consistent with this, chromatin
      immunoprecipitation assays directed at mesodermal genes demonstrate that Geminin
      promotes Polycomb binding and Polycomb-mediated repressive histone modifications,
      while inhibiting modifications associated with gene activation. This work defines
      Geminin as an essential regulator of the embryonic transition from pluripotency
      through early multi-lineage commitment, and demonstrates that functional
      cooperativity between Geminin and Polycomb contributes to this process.

PMID- 21098564
TI  - The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration.
AB  - Identification of the signaling pathways that control the proliferation of stem
      cells (SCs), and whether they act in a cell or non-cell autonomous manner, is key
      to our understanding of tissue homeostasis and cancer. In the adult Drosophila
      midgut, the Jun N-Terminal Kinase (JNK) pathway is activated in damaged
      enterocyte cells (ECs) following injury. This leads to the production of Upd
      cytokines from ECs, which in turn activate the Janus kinase (JAK)/Signal
      transducer and activator of transcription (STAT) pathway in Intestinal SCs
      (ISCs), stimulating their proliferation. In addition, the Hippo pathway has been
      recently implicated in the regulation of Upd production from the ECs. Here, we
      show that the Hippo pathway target, Yorkie (Yki), also plays a crucial and cell
      autonomous role in ISCs. Activation of Yki in ISCs is sufficient to increase ISC
      proliferation, a process involving Yki target genes that promote division,
      survival and the Upd cytokines. We further show that prior to injury, Yki
      activity is constitutively repressed by the upstream Hippo pathway members Fat
      and Dachsous (Ds). These findings demonstrate a cell-autonomous role for the
      Hippo pathway in SCs, and have implications for understanding the role of this
      pathway in tumorigenesis and cancer stem cells.

PMID- 21098563
TI  - A conserved germline multipotency program.
AB  - The germline of multicellular animals is segregated from somatic tissues, which
      is an essential developmental process for the next generation. Although certain
      ecdysozoans and chordates segregate their germline during embryogenesis, animals
      from other taxa segregate their germline after embryogenesis from multipotent
      progenitor cells. An overlapping set of genes, including vasa, nanos and piwi,
      operate in both multipotent precursors and in the germline. As we propose here,
      this conservation implies the existence of an underlying germline multipotency
      program in these cell types that has a previously underappreciated and conserved
      function in maintaining multipotency.

PMID- 21098566
TI  - A functionally conserved boundary element from the mouse HoxD locus requires GAGA
      factor in Drosophila.
AB  - Hox genes are necessary for proper morphogenesis and organization of various body
      structures along the anterior-posterior body axis. These genes exist in clusters
      and their expression pattern follows spatial and temporal co-linearity with
      respect to their genomic organization. This colinearity is conserved during
      evolution and is thought to be constrained by the regulatory mechanisms that
      involve higher order chromatin structure. Earlier studies, primarily in
      Drosophila, have illustrated the role of chromatin-mediated regulatory processes,
      which include chromatin domain boundaries that separate the domains of distinct
      regulatory features. In the mouse HoxD complex, Evx2 and Hoxd13 are located ~ 9
      kb apart but have clearly distinguishable temporal and spatial expression
      patterns. Here, we report the characterization of a chromatin domain boundary
      element from the Evx2-Hoxd13 region that functions in Drosophila as well as in
      mammalian cells. We show that the Evx2-Hoxd13 region has sequences conserved
      across vertebrate species including a GA repeat motif and that the Evx2-Hoxd13
      boundary activity in Drosophila is dependent on GAGA factor that binds to the GA
      repeat motif. These results show that Hox genes are regulated by chromatin
      mediated mechanisms and highlight the early origin and functional conservation of
      such chromatin elements.

PMID- 21098565
TI  - Initiation of trophectoderm lineage specification in mouse embryos is independent
      of Cdx2.
AB  - The separation of the first two lineages - trophectoderm (TE) and inner cell mass
      (ICM) - is a crucial event in the development of the early embryo. The ICM, which
      constitutes the pluripotent founder cell population, develops into the embryo
      proper, whereas the TE, which comprises the surrounding outer layer, supports the
      development of the ICM before and after implantation. Cdx2, the first
      transcription factor expressed specifically in the developing TE, is crucial for
      the differentiation of cells into the TE, as lack of zygotic Cdx2 expression
      leads to a failure of embryos to hatch and implant into the uterus. However,
      speculation exists as to whether maternal Cdx2 is required for initiation of TE
      lineage separation. Here, we show that effective elimination of both maternal and
      zygotic Cdx2 transcripts by an RNA interference approach resulted in failure of
      embryo hatching and implantation, but the developing blastocysts exhibited normal
      gross morphology, indicating that TE differentiation had been initiated.
      Expression of keratin 8, a marker for differentiated TE, further confirmed the
      identity of the TE lineage in Cdx2-deficient embryos. However, these embryos
      exhibited low mitochondrial activity and abnormal ultrastructure, indicating that
      Cdx2 plays a key role in the regulation of TE function. Furthermore, we found
      that embryonic compaction does not act as a 'switch' regulator to turn on Cdx2
      expression. Our results clearly demonstrate that neither maternal nor zygotic
      Cdx2 transcripts direct the initiation of ICM/TE lineage separation.

PMID- 21098567
TI  - Collagen XIXa1 is crucial for motor axon navigation at intermediate targets.
AB  - During development, motor axons navigate from the spinal cord to their muscle
      targets in the periphery using stereotyped pathways. These pathways are broken
      down into shorter segments by intermediate targets where axon growth cones are
      believed to coordinate guidance cues. In zebrafish stumpy mutants, embryonic
      development proceeds normally; however, as trunk motor axons stall at their
      intermediate targets, suggesting that Stumpy is needed specifically for motor
      axon growth cones to proceed past intermediate targets. Fine mapping and
      positional cloning revealed that stumpy was the zebrafish homolog of the atypical
      FACIT collagen collagenXIXa1 (colXIX). colXIX expression was observed in a
      temporal and spatial pattern, consistent with a role in motor axon guidance at
      intermediate targets. Knocking down zebrafish ColXIX phenocopied the stumpy
      phenotype and this morpholino phenotype could be rescued by adding back either
      mouse or zebrafish colXIX RNA. The stumpy phenotype was also partially rescued in
      mutants by first knocking down zebrafish ColXIX and adding back colXIX RNA,
      suggesting that the mutation is acting as a dominant negative. Together, these
      results demonstrate a novel function for a FACIT collagen in guiding vertebrate
      motor axons through intermediate targets.

PMID- 21098569
TI  - Developmental origins of precocial forelimbs in marsupial neonates.
AB  - Marsupial mammals are born in an embryonic state, as compared with their
      eutherian counterparts, yet certain features are accelerated. The most
      conspicuous of these features are the precocial forelimbs, which the newborns use
      to climb unaided from the opening of the birth canal to the teat. The
      developmental mechanisms that produce this acceleration are unknown. Here we show
      that heterochronic and heterotopic changes early in limb development contribute
      to forelimb acceleration. Using Tbx5 and Tbx4 as fore- and hindlimb field
      markers, respectively, we have found that, compared with mouse, both limb fields
      arise notably early during opossum development. Patterning of the forelimb buds
      is also accelerated, as Shh expression appears early relative to the outgrowth of
      the bud itself. In addition, the forelimb fields and forelimb myocyte allocation
      are increased in size and number, respectively, and migration of the spinal
      nerves into the forelimb bud has been modified. This shift in the extent of the
      forelimb field is accompanied by shifts in Hox gene expression along the anterior
      posterior axis. Furthermore, we found that both fore- and hindlimb fields arise
      gradually during gastrulation and extension of the embryonic axis, in contrast to
      the appearance of the limb fields in their entirety in all other known cases. Our
      results show a surprising evolutionary flexibility in the early limb development
      program of amniotes and rule out the induction of the limb fields by mature
      structures such as the somites or mesonephros.

PMID- 21098568
TI  - Foxj1 regulates floor plate cilia architecture and modifies the response of cells
      to sonic hedgehog signalling.
AB  - Sonic hedgehog signalling is essential for the embryonic development of many
      tissues including the central nervous system, where it controls the pattern of
      cellular differentiation. A genome-wide screen of neural progenitor cells to
      evaluate the Shh signalling-regulated transcriptome identified the forkhead
      transcription factor Foxj1. In both chick and mouse Foxj1 is expressed in the
      ventral midline of the neural tube in cells that make up the floor plate.
      Consistent with the role of Foxj1 in the formation of long motile cilia, floor
      plate cells produce cilia that are longer than the primary cilia found elsewhere
      in the neural tube, and forced expression of Foxj1 in neuroepithelial cells is
      sufficient to increase cilia length. In addition, the expression of Foxj1 in the
      neural tube and in an Shh-responsive cell line attenuates intracellular
      signalling by decreasing the activity of Gli proteins, the transcriptional
      mediators of Shh signalling. We show that this function of Foxj1 depends on
      cilia. Nevertheless, floor plate identity and ciliogenesis are unaffected in
      mouse embryos lacking Foxj1 and we provide evidence that additional transcription
      factors expressed in the floor plate share overlapping functions with Foxj1.
      Together, these findings identify a novel mechanism that modifies the cellular
      response to Shh signalling and reveal morphological and functional features of
      the amniote floor plate that distinguish these cells from the rest of the
      neuroepithelium.

PMID- 21098570
TI  - Epithelial dynamics of pancreatic branching morphogenesis.
AB  - The mammalian pancreas is a highly branched gland, essential for both digestion
      and glucose homeostasis. Pancreatic branching, however, is poorly understood,
      both at the ultrastructural and cellular levels. In this article, we characterize
      the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of
      their epithelial organization. We identify trends in pancreatic branch morphology
      and introduce a novel mechanism for branch formation, which involves transient
      epithelial stratification and partial loss of cell polarity, changes in cell
      shape and cell rearrangements, de novo tubulogenesis and epithelial tubule
      remodeling. In contrast to the classical epithelial budding and tube extension
      observed in other organs, a pancreatic branch takes shape as a multi-lumen
      tubular plexus coordinately extends and remodels into a ramifying, single-lumen
      ductal system. Moreover, our studies identify a role for EphB signaling in
      epithelial remodeling during pancreatic branching. Overall, these results
      illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium
      shapes itself to create a functional branching organ.

PMID- 21098571
TI  - The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal
      signaling in the first pharyngeal arch.
AB  - Neural crest cells (NCCs) are a subset of multipotent, migratory stem cells that
      populate a large number of tissues during development and are important for
      craniofacial and cardiac morphogenesis. Although microRNAs (miRNAs) have emerged
      as important regulators of development and disease, little is known about their
      role in NCC development. Here, we show that loss of miRNA biogenesis by NCC
      specific disruption of murine Dicer results in embryos lacking craniofacial
      cartilaginous structures, cardiac outflow tract septation and thymic and dorsal
      root ganglia development. Dicer mutant embryos had reduced expression of Dlx2, a
      transcriptional regulator of pharyngeal arch development, in the first pharyngeal
      arch (PA1). miR-452 was enriched in NCCs, was sufficient to rescue Dlx2
      expression in Dicer mutant pharyngeal arches, and regulated non-cell-autonomous
      signaling involving Wnt5a, Shh and Fgf8 that converged on Dlx2 regulation in PA1.
      Correspondingly, knockdown of miR-452 in vivo decreased Dlx2 expression in the
      mandibular component of PA1, leading to craniofacial defects. These results
      suggest that post-transcriptional regulation by miRNAs is required for
      differentiation of NCC-derived tissues and that miR-452 is involved in epithelial
      mesenchymal signaling in the pharyngeal arch.

PMID- 21098572
TI  - The receptor-like kinase KLAVIER mediates systemic regulation of nodulation and
      non-symbiotic shoot development in Lotus japonicus.
AB  - In legumes, the number of symbiotic root nodules is controlled by long-distance
      communication between the shoot and the root. Mutants defective in this feedback
      mechanism exhibit a hypernodulating phenotype. Here, we report the identification
      of a novel leucine-rich repeat receptor-like kinase (LRR-RLK), KLAVIER (KLV),
      which mediates the systemic negative regulation of nodulation in Lotus japonicus.
      In leaf, KLV is predominantly expressed in the vascular tissues, as with another
      LRR-RLK gene, HAR1, which also regulates nodule number. A double-mutant analysis
      indicated that KLV and HAR1 function in the same genetic pathway that governs the
      negative regulation of nodulation. LjCLE-RS1 and LjCLE-RS2 represent potential
      root-derived mobile signals for the HAR1-mediated systemic regulation of
      nodulation. Overexpression of LjCLE-RS1 or LjCLE-RS2 did not suppress the
      hypernodulation phenotype of the klv mutant, indicating that KLV is required and
      acts downstream of LjCLE-RS1 and LjCLE-RS2. In addition to the role of KLV in
      symbiosis, complementation tests and expression analyses indicated that KLV plays
      multiple roles in shoot development, including maintenance of shoot apical
      meristem, vascular continuity, shoot growth and promotion of flowering.
      Biochemical analyses using transient expression in Nicotiana benthamiana revealed
      that KLV has the ability to interact with HAR1 and with itself. Together, these
      results suggest that the potential KLV-HAR1 receptor complex regulates symbiotic
      nodule development and that KLV is also a key component in other signal
      transduction pathways that mediate non-symbiotic shoot development.

PMID- 21098574
TI  - CXCL13: a novel biomarker of B-cell return following rituximab treatment and
      synovitis in patients with rheumatoid arthritis.
AB  - OBJECTIVES: The B-cell chemokine, CXCL13, is a proposed serum biomarker of
      synovitis in RA. Its behaviour in the context of B-cell depletion therapy and
      reconstitution was studied during treatment of RA with rituximab. METHODS: Serum
      samples from 20 RA patients were analysed for CXCL13, RF-IgM and anti-CCP by
      ELISA before and 2 and 6 months following rituximab treatment. B cells were
      monitored by flow cytometry. Gene expression in blood and synovial biopsies was
      determined by qPCR. RESULTS: Patients with detectable B cells at 6 months had
      significantly higher levels of CXCL13 and RF-IgM and slightly higher levels of
      anti-CCP throughout the study, including at baseline, compared with patients with
      undetectable B cells at 6 months. Conversely, 10 of 12 patients with high
      baseline CXCL13 had detectable circulating B cells at 6 months, whereas no B
      cells could be detected at 6 months in patients with low baseline CXCL13.
      Synovial CXCL13 expression at baseline correlated significantly with serum CXCL13
      levels, and the synovium of patients with high serum CXCL13 expressed elevated
      levels of IL-1beta, IL-8, MMP1 and MMP3. In addition, synovial CXCL13 expression
      correlated significantly with several synovial inflammatory markers. CONCLUSIONS:
      Serum CXCL13 is predictive of the rate of B-cell repopulation following a course
      of rituximab in RA. Serum CXCL13 correlates with synovial CXCL13 measured at a
      single joint, suggesting synovitis as an important source of circulating CXCL13.
      Within the synovium, CXCL13 expression is highly correlated with markers of
      synovitis. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/,
      NCT00147966.

PMID- 21098573
TI  - Assessment of bone remodelling in childhood-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To identify predictors of bone remodelling in children and young
      adults with SLE. METHODS: Ninety subjects with SLE aged 8-22 years underwent
      yearly measurements of height, bone age, bone turnover markers, serum Type I
      IFNs, SLEDAI and BMD. Predictors of bone turnover were examined using serum
      osteocalcin as a marker of bone formation and both serum tartrate-resistant acid
      phosphatase (TRAP) and urine N-telopeptide (NTx) as markers of bone resorption.
      RESULTS: Subjects demonstrated short stature, high BMI and bone age delay. A
      spine BMD Z-score of less than -2.0 was seen in 16.1% of subject visits. Serum
      osteocalcin was negatively correlated with glucocorticoid dose (Spearman rank
      correlation coefficient R = -0.34, P < 0.0001) but was not associated with SLEDAI
      after adjustment for confounders. Serum TRAP was negatively associated with
      SLEDAI, even after controlling for confounders (P = 0.04). Similar results were
      obtained for urine NTx. There was a negative association between TRAP and serum
      IFN-beta (P = 0.03). CONCLUSIONS: In this population of children and young adults
      with moderate lupus disease activity, glucocorticoid dose was a negative
      predictor of bone formation, whereas lupus disease activity was not.
      Interestingly, lupus disease activity was a negative predictor of bone
      resorption, suggesting that lupus disease activity is not the primary factor
      contributing to the bone deficits of childhood-onset SLE. The potential
      protective role of IFN-beta and the effects of SLE treatment on bone loss require
      further study.

PMID- 21098575
TI  - Beneficial and harmful effects of shoulder arthroplasty in patients with
      rheumatoid arthritis: results from a Cochrane review.
AB  - OBJECTIVE: To assess beneficial and harmful effects of arthroplasty in the
      shoulder joint in patients with RA. METHODS: A systematic review within the
      framework of the Cochrane Collaboration identified randomized controlled trials
      (RCTs), controlled clinical trials and case series (included for assessment of
      complications) published between 1995 and 2008. Articles considered potentially
      relevant were retrieved in full text and assessed independently by two authors.
      Risk of bias and level of evidence were assessed according to the established
      criteria. RESULTS: One RCT (26 shoulders) compared cemented and uncemented
      humeral stem fixation during arthroplasty, reporting no significant differences
      between groups at 2-year follow-up (low-quality evidence). Nineteen case series
      (1155 shoulders) reported component loosening requiring revision at 5%,
      infections at 2% and minor complications at 7% (very low-quality evidence). The
      retrospective case series had several limitations related to methodological
      quality and standards of reporting. CONCLUSION: At present, there is very little
      research evidence supporting decisions about shoulder joint arthroplasty in
      patients with RA.

PMID- 21098576
TI  - Improved diabetic control in advanced heart failure patients treated with left
      ventricular assist devices.
AB  - AIMS: Left ventricular assist devices (LVADs) are increasingly used as
      therapeutic options for patients with advanced congestive heart failure (CHF),
      many of whom suffer from diabetes mellitus (DM). The aim of this study was to
      evaluate the effect of restoration of normal cardiac output using LVAD support on
      diabetes control in patients with advanced CHF. METHODS AND RESULTS: A
      retrospective chart review of all clinic patients supported with long-term LVADs
      between July 2008 and July 2009 at Columbia University Medical Center was
      performed. Patients with DM diagnosed prior to device implantation were included
      in this analysis. Clinical and laboratory data within 1 month preceding and 6
      months following LVAD implantation were collected. Of 43 LVAD patients followed
      in our clinic during the study period, 15 had a diagnosis of DM. Thirteen of the
      15 patients were male, mean age was 63 +/- 11 years, and the pre-LVAD left
      ventricular ejection fraction (LVEF) was 16.5 +/- 5.7%. Fasting glucose levels,
      HbA1c, and daily insulin requirement within 1 month before and an average of 4.0
      +/- 2.3 months after LVAD placement were 157.7 +/- 50.6 vs. 104.1 +/- 21.4 mg/dL,
      7.7 +/- 0.9 vs. 6.0 +/- 0.8.%, and 53.3 +/- 51.7 vs. 24.2 +/- 27.2 IU,
      respectively (P < 0.05 for all comparisons). Six of the 15 patients were
      completely free of antidiabetic medications and had blood glucose < 126 mg/dL as
      well as HbA1c < 6% after LVAD. Body mass index (BMI) was slightly increased after
      LVAD (28.7 +/- 5.3 vs. 30.2 +/- 4.1 kg/m2, P NS). CONCLUSION: Restoration of
      normal cardiac output after LVAD implantation improves diabetic control in
      patients with advanced CHF. Additional studies are warranted to determine the
      mechanisms that worsen or possibly induce DM in patients with advanced CHF.

PMID- 21098578
TI  - On energy circuits in the failing myocardium.

PMID- 21098577
TI  - Natriuretic peptide-guided management by the general practitioner: how to
      interpret the SIGNAL.

PMID- 21098579
TI  - Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure.
AB  - AIMS: Several studies have shown that muscle mass loss is an important pathogenic
      issue in heart failure (HF). Atrogin-1 is a F-box protein selectively expressed
      in cardiac and skeletal muscle tissue, which plays a pivotal role in muscle
      wasting regulation. The aim of this study was to investigate the expression of
      Atrogin-1 and the molecular pathway involved in Atrogin-1 regulation in human HF.
      METHODS AND RESULTS: Cardiac tissue from patients with HF (HF group: n=10) or
      with normal left ventricular function (control group: n=9) was studied by western
      blot and real time-PCR analysis. Linear regression analysis between patients left
      ventricular ejection fraction (LVEF) and Atrogin1 or its regulator Forkhead box O
      3a (Foxo3a) myocardial expression was performed to test correlations between
      protein expression and LVEF. Western blot analysis revealed that the myocardial
      expression of Atrogin-1 in the HF group was 2.5-fold increased compared with
      controls (P=0.007). Accordingly, Atrogin-1 mRNA was 1.5 higher than in controls
      (P=0.003). The expression of Foxo3a and its up-stream regulator AKT were also
      measured. Western blot analysis demonstrated in the HF group a 2.56-fold
      reduction of AKT phosphorylation and a 3.32-fold increase of Foxo3a as compared
      with controls (P=0.002 and P=0.001, respectively). Finally, linear regression
      showed a significant relationship between Foxo3a or Atrogin-1 expression and LVEF
      (R=0.976, P<0.0001 and R=0.895, P=0.003, respectively). CONCLUSION: Our results
      suggest that in human HF, the activity of AKT decreases, with activation of
      Foxo3a and induction of Atrogin-1, thereby leading to a molecular state that
      favours heart muscle loss and left ventricular dysfunction.

PMID- 21098582
TI  - Myostatin serum levels in heart failure.

PMID- 21098583
TI  - Potential mechanisms of retronasal odor referral to the mouth.
AB  - The current study took a first step toward elucidating the sensory input that
      drives retronasal odor referral to the mouth. In 2 experiments, subjects
      performed odor localization tasks under various oral-nasal stimulation conditions
      that allowed us to assess the effects of direction of airflow, taste, and tactile
      stimulation on retronasal odor referral. Subjects reported the locations of
      perceived odors when food odorants were inhaled through the mouth alone or in the
      presence of water or various tastants in the mouth. The results indicated that
      when perceived alone, vanilla and soy sauce odor were localized 54.7%: 26.4%:
      18.9% and 60.0%: 21.7%: 18.3% in the nose, oral cavity, and on the tongue,
      respectively. The localization of odors alone was not significantly different
      from when water was presented simultaneously in the mouth, indicating that
      tactile stimulation itself is not sufficient to enhance odor referral. However,
      the presence of sucrose, but not other tastes, significantly increased
      localization of vanilla to the tongue. Likewise, only NaCl significantly
      augmented referral of soy sauce odor to the tongue. These data indicate that
      referral of retronasal odors to the mouth can occur in the absence of a either
      taste or touch but that referral to the tongue depends strongly on the presence
      of a congruent taste.

PMID- 21098584
TI  - Pheromone detection by a pheromone emitter: a small sex pheromone-specific
      processing system in the female American cockroach.
AB  - Many animals depend on pheromone communication for successful mating. Sex
      pheromone in insects is usually released by females to attract males. In American
      cockroaches, the largest glomerulus (B-glomerulus) in the male antennal lobe
      (first-order olfactory center) processes the major component of sex pheromone.
      Using intracellular recordings combined with fine neuroanatomical techniques, we
      provide evidence that the female homolog of the male B-glomerulus also acts as a
      sex pheromone-specific detector. Whereas ordinary glomeruli that process normal
      environmental odors are innervated by single projection neurons (PNs), the B
      glomerulus in both sexes is innervated by multiple PNs, one of which possesses a
      thicker axon, termed here B-PN. Both soma size and axon diameter were smaller on
      B-PNs from females compared with B-PNs from males. The female B-PNs also produce
      fewer terminal arborizations in the protocerebrum than male B-PNs. Termination
      fields in the lateral protocerebrum of the female B-PN are mostly segregated from
      those formed by other uniglomerular PNs innervating ordinary glomeruli. Female B
      PN activity was greatest in response to sex pheromone but lower than that in the
      male B-PN. This specific detection system suggests that sex pheromone affects the
      behavior and/or endocrine system of female cockroaches.

PMID- 21098586
TI  - Use of skin lightening creams.

PMID- 21098589
TI  - A quarter of patients in some European hospitals acquire infections.

PMID- 21098580
TI  - Telemedical Interventional Monitoring in Heart Failure (TIM-HF), a randomized,
      controlled intervention trial investigating the impact of telemedicine on
      mortality in ambulatory patients with heart failure: study design.
AB  - AIMS: Remote patient management (telemonitoring) may help to detect early signs
      of cardiac decompensation, allowing optimization of and adherence to treatments
      in chronic heart failure (CHF). Two meta-analyses have suggested that
      telemedicine in CHF can reduce mortality by 30-35%. The aim of the TIM-HF study
      was to investigate the impact of telemedical management on mortality in
      ambulatory CHF patients. Methods CHF patients [New York Heart Association (NYHA)
      II/III, left ventricular ejection fraction (LVEF)<=35%] with a history of cardiac
      decompensation with hospitalization in the past or therapy with intravenous
      diuretics in the prior 24 months (no decompensation required if LVEF<=25%) were
      randomized 1:1 to an intervention group of daily remote device monitoring
      (electrocardiogram, blood pressure, body weight) coupled with medical telephone
      support or to usual care led by the patients' local physician. In the
      intervention group, 24/7 physician-led medical support was provided by two
      central telemedical centres. A clinical event committee blinded to treatment
      allocation assessed cause of death and reason for hospitalization. The primary
      endpoint was total mortality. The first secondary endpoint was a composite of
      cardiovascular mortality or hospitalization due to heart failure. Other secondary
      endpoints included cardiovascular mortality, all-cause and cause-specific
      hospitalizations (all time to first event) as well as days lost due to heart
      failure hospitalization or cardiovascular death (in % of follow-up time), and
      changes in quality of life and NYHA class. Overall, 710 CHF patients were
      recruited. The mean follow-up was 21.5+/-7.2 months, with a minimum of 12 months.
      Perspective The study will provide important prospective outcome data on the
      impact of telemedical management in patients with CHF.

PMID- 21098590
TI  - Obsolete clinical signs. Signs of the times.

PMID- 21098591
TI  - Measuring patient satisfaction. Theoretical foundation needed.

PMID- 21098592
TI  - Opiate substitution and death. GPs need guidance, please.

PMID- 21098593
TI  - Decision aids and screening. Editorial was amoral.

PMID- 21098594
TI  - Decision aids and screening. Information v promotion.

PMID- 21098595
TI  - Sticky labels. Labels unstuck.

PMID- 21098598
TI  - Forcing treatment on patients. Guidelines, please.

PMID- 21098599
TI  - International tobacco control. Still some way to go in China.

PMID- 21098600
TI  - Obesity related illness. Beware swallowing whole.

PMID- 21098601
TI  - GP haemoglobinopathy screening. One more thing for GPs.

PMID- 21098602
TI  - GP haemoglobinopathy screening. GPs may not be the answer.

PMID- 21098603
TI  - GP haemoglobinopathy screening. Coding issues at the coalface.

PMID- 21098604
TI  - Seeking treatment abroad. Challenge of migrating patients.

PMID- 21098607
TI  - Think rationally rather than intuitively to avoid diagnostic errors, doctors are
      told.

PMID- 21098608
TI  - More than a billion people can't afford costs of healthcare, says WHO.

PMID- 21098609
TI  - Pope's comment on condom use will help HIV prevention, say activists.

PMID- 21098612
TI  - Intravenous thrombolysis for stroke.

PMID- 21098613
TI  - Alcohol and heart disease.

PMID- 21098614
TI  - Thrombolysis in very elderly people: controlled comparison of SITS International
      Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive.
AB  - OBJECTIVE: To assess effect of age on response to alteplase in acute ischaemic
      stroke. DESIGN: Adjusted controlled comparison of outcomes between non-randomised
      patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel
      Haenszel test and proportional odds logistic regression analysis. SETTING:
      Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and
      Virtual International Stroke Trials Archive (VISTA). PARTICIPANTS: 23 334
      patients from SITS-ISTR (December 2002 to November 2009) who underwent
      thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not
      undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80
      ("elderly," mean 84.6), data on 272 patients were missing for baseline National
      Institutes of Health stroke severity score, leaving 29 228 patients for analysis
      adjusted for age and baseline severity. MAIN OUTCOME MEASURES: Functional
      outcomes at 90 days measured by score on modified Rankin scale. RESULTS: Median
      severity at baseline was the same for patients who underwent thrombolysis and
      controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29
      228). The distribution of scores on the modified Rankin scale was better among
      all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval
      1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred
      independently among patients aged <=80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and
      in those aged >80 (1.4, 1.3 to 1.6; P<0.001; n=3439). Odds ratios were consistent
      across all 10 year age ranges above 30, and benefit was significant from age 41
      to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3
      6; and 6 (death) v rest) were consistent with the results of the ordinal
      analysis. CONCLUSIONS: Outcome in patients with acute ischaemic stroke is
      significantly better in those who undergo thrombolysis compared with those who do
      not. Increasing age is associated with poorer outcome but the association between
      thrombolysis treatment and improved outcome is maintained in very elderly people.
      Age alone should not be a barrier to treatment.

PMID- 21098616
TI  - Is early retirement good for your health?

PMID- 21098615
TI  - Patterns of alcohol consumption and ischaemic heart disease in culturally
      divergent countries: the Prospective Epidemiological Study of Myocardial
      Infarction (PRIME).
AB  - OBJECTIVE: To investigate the effect of alcohol intake patterns on ischaemic
      heart disease in two countries with contrasting lifestyles, Northern Ireland and
      France. DESIGN: Cohort data from the Prospective Epidemiological Study of
      Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption,
      incidence of binge drinking (alcohol >50 g on at least one day a week), incidence
      of regular drinking (at least one day a week, and alcohol <50 g if on only one
      occasion), volume of alcohol intake, frequency of consumption, and types of
      beverage consumed were assessed once at inclusion. All coronary events that
      occurred during the 10 year follow-up were prospectively registered. The relation
      between baseline characteristics and incidence of hard coronary events and angina
      events was assessed by Cox's proportional hazards regression analysis. SETTING:
      One centre in Northern Ireland (Belfast) and three centres in France (Lille,
      Strasbourg, and Toulouse). PARTICIPANTS: 9778 men aged 50-59 free of ischaemic
      heart disease at baseline, who were recruited between 1991 and 1994. MAIN OUTCOME
      MEASURES: Incident myocardial infarction and coronary death ("hard" coronary
      events), and incident angina pectoris. RESULTS: A total of 2405 men from Belfast
      and 7373 men from the French centres were included in the analyses, 1456 (60.5%)
      and 6679 (90.6%) of whom reported drinking alcohol at least once a week,
      respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol
      every day compared with 75% (5008/6679) of men in France. Mean alcohol
      consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers
      comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples,
      respectively. A total of 683 (7.0%) of the 9778 participants experienced
      ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard
      coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary
      events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in
      Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment
      for classic cardiovascular risk factors and centre, the hazard ratio for hard
      coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for
      binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI
      1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for
      hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to
      2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for
      alcohol patterns and wine drinking. Only wine drinking was associated with a
      lower risk of hard coronary events, irrespective of the country. CONCLUSIONS:
      Regular and moderate alcohol intake throughout the week, the typical pattern in
      middle aged men in France, is associated with a low risk of ischaemic heart
      disease, whereas the binge drinking pattern more prevalent in Belfast confers a
      higher risk.

PMID- 21098617
TI  - Effect of retirement on major chronic conditions and fatigue: French GAZEL
      occupational cohort study.
AB  - OBJECTIVES: To determine, using longitudinal analyses, if retirement is followed
      by a change in the risk of incident chronic diseases, depressive symptoms, and
      fatigue. Design Prospective study with repeat measures from 7 years before to 7
      years after retirement. SETTING: Large French occupational cohort (the GAZEL
      study), 1989-2007. Participants 11 246 men and 2858 women. MAIN OUTCOME MEASURES:
      Respiratory disease, diabetes, coronary heart disease and stroke, mental fatigue,
      and physical fatigue, measured annually by self report over the 15 year
      observation period; depressive symptoms measured at four time points. RESULTS:
      The average number of repeat measurements per participant was 12.1. Repeated
      measures logistic regression with generalised estimating equations showed that
      the cumulative prevalence of self reported respiratory disease, diabetes, and
      coronary heart disease and stroke increased with age, with no break in the trend
      around retirement. In contrast, retirement was associated with a substantial
      decrease in the prevalence of both mental fatigue (odds ratio for fatigue one
      year after versus one year before retirement 0.19, 95% confidence interval 0.18
      to 0.21) and physical fatigue (0.27, 0.26 to 0.30). A major decrease was also
      observed in depressive symptoms (0.60, 0.53 to 0.67). The decrease in fatigue
      around retirement was more pronounced among people with a chronic disease before
      retirement. CONCLUSIONS: Longitudinal modelling of repeat data showed that
      retirement did not change the risk of major chronic diseases but was associated
      with a substantial reduction in mental and physical fatigue and depressive
      symptoms, particularly among people with chronic diseases.

PMID- 21098618
TI  - Circulating free DNA and p53 antibodies in plasma of patients with ovarian
      epithelial cancers.
AB  - BACKGROUND: This study was conducted in order to evaluate the significance of
      circulating free DNA (CFDNA), blood plasma p53 antibodies (p53-Ab) and mutations
      of KRAS gene in the prognosis of ovarian epithelial cancers. PATIENTS AND
      METHODS: A total of 126 patients were included in this study. KRAS mutations and
      CFDNA were detected by means of the PCR-restriction fragment length polymorphism
      (PCR-RFLP) and enriched by the PCR-RFLP method. Enzyme-linked immunosorbent assay
      was used to analyze plasma p53-Ab. RESULTS: KRAS mutations were detected in 27
      (21.4%) of examined tumors. The frequency of KRAS mutations was especially high
      in mucinous cancers (P < 0.001). CFDNA and p53-Ab were frequently detected in
      patients with serous cancers in high grade (P < 0.001). The overall survival rate
      was significantly lower for patients with serous tumors and CFDNA and p53-Ab
      positive than negative tumors (P = 0.022 and P < 0.001, respectively). In
      mucinous ovarian cancer, a worse overall survival was correlated with the KRAS
      mutations (P = 0.03). CONCLUSIONS: The results of the present study suggested
      that a presence of KRAS mutations in mucinous ovarian cancer and CFDNA and p53-Ab
      in serous tumors was correlated with the highest risk of cancer progression.

PMID- 21098619
TI  - Adjuvant chemotherapy for rectal cancer.

PMID- 21098620
TI  - Spatial organization of neurons in the frontal pole sets humans apart from great
      apes.
AB  - Few morphological differences have been identified so far that distinguish the
      human brain from the brains of our closest relatives, the apes. Comparative
      analyses of the spatial organization of cortical neurons, including minicolumns,
      can aid our understanding of the functionally relevant aspects of microcircuitry.
      We measured horizontal spacing distance and gray-level ratio in layer III of 4
      regions of human and ape cortex in all 6 living hominoid species: frontal pole
      (Brodmann area [BA] 10), and primary motor (BA 4), primary somatosensory (BA 3),
      and primary visual cortex (BA 17). Our results identified significant differences
      between humans and apes in the frontal pole (BA 10). Within the human brain,
      there were also significant differences between the frontal pole and 2 of the 3
      regions studied (BA 3 and BA 17). Differences between BA 10 and BA 4 were present
      but did not reach significance. These findings in combination with earlier
      findings on BA 44 and BA 45 suggest that human brain evolution was likely
      characterized by an increase in the number and width of minicolumns and the space
      available for interconnectivity between neurons in the frontal lobe, especially
      the prefrontal cortex.

PMID- 21098621
TI  - Community rehabilitation for older people: day hospital or home-based services?

PMID- 21098622
TI  - The internalized stigma experienced by members of a mental health advocacy group
      in South Africa.
AB  - BACKGROUND: Although there is a growing literature on internalized stigma from
      the developed world, very little research has been conducted in developing
      countries such as South Africa. Therefore, the purpose of this study was to
      describe the internalized stigma experienced by members of a mental health
      advocacy group in South Africa and relationships between self-stigma and other
      constructs, namely, empowerment, perceived devaluation and discrimination.
      METHODS: Self-administered questionnaires measuring respondents reported levels
      of internalized stigma, empowerment and perceived devaluation and discrimination
      were distributed to all the members of the South African Depression & Anxiety
      Group (SADAG) by post and via email. Of the 850 members invited to participate,
      142 members of SADAG completed the questionnaire. Pearson correlations were
      computed and multiple regression analyses were carried out to analyse the data.
      RESULTS: The highest reports of stigma were for stigma resistance (mean = 2.9),
      alienation (mean = 2.47) and perceived discrimination (mean = 2.24). Low levels
      of stereotype endorsement (mean = 1.77) and social withdrawal (mean = 1.22) were
      reported. Although respondents often felt that the public held negative attitudes
      towards individuals suffering with a mental illness (perceived devaluation and
      discrimination scale (PDD), mean = 2.95), a majority of respondents reported high
      levels of empowerment (mean = 3.0) and self-efficacy (mean = 2.47). After
      controlling for socio-demographic factors, higher scores on the PDD were
      associated with social withdrawal and having experienced discrimination.
      CONCLUSION: Internalization of stigma, disempowerment and loss of self-esteem are
      not inevitable consequences for all individuals with a mental illness.
      Nevertheless, perceived stigma is significantly associated with social withdrawal
      and experienced discrimination.

PMID- 21098623
TI  - Smoking and alcohol use during pregnancy and age of menarche in daughters.
AB  - BACKGROUND: We assessed whether exposure to prenatal smoking or alcohol
      accelerates age of menarche (AOM) in offspring. METHODS: We studied a Danish
      cohort of 3169 singleton females born in April 1984-April 1987. Linear
      regressions were conducted to examine associations between prenatal smoking or
      alcohol exposure and offspring's AOM on: (i) the daughters who provided data on
      both month and the year of menarche (n= 1634) and (ii) the entire sample that
      provided at least the year of menarche (n= 3169). We also examined associations
      between only pre-pregnancy smoking or childhood exposure to smoking and AOM. The
      full model was adjusted for maternal pre-pregnancy body mass index, maternal age
      at childbirth, parental socio-economic status, parity, consumption of milk
      products during pregnancy and marital status. RESULTS: Among those who provided
      both year and month, AOM was accelerated by 2.8 months (95% CI in months: -5.3, 
      0.4) among those exposed to 10+ cigarettes/day throughout pregnancy and by 4.1
      months (95% CI in months: -7.7, -0.5) among those with mothers who quit smoking
      sometime during pregnancy, compared with the unexposed group after adjustment for
      covariates. Similar, but much weaker, associations were observed among girls
      whose mothers smoked 1-9 cigarettes/day throughout pregnancy or whose fathers
      smoked compared with their unexposed counterparts after adjustment for covariates
      [-0.8 months (95% CI: -2.6, 1.0)]. No associations were observed between AOM and
      only pre-pregnancy smoking or only childhood exposure or prenatal alcohol
      exposure. CONCLUSIONS: Our study indicates that heavy smoking throughout the
      pregnancy may be important in prenatal programming of AOM.

PMID- 21098624
TI  - CTGF expression is up-regulated by PROK1 in early pregnancy and influences HTR
      8/Svneo cell adhesion and network formation.
AB  - BACKGROUND: Prokineticin-1 (PROK1) and connective tissue growth factor (CTGF) are
      expressed in human endometrium and first-trimester decidua and have individually
      been proposed to have roles in implantation and placentation. We have recently
      demonstrated that CTGF may be a target gene for PROK1 in gene array analysis of a
      prokineticin receptor-1 stably transfected Ishikawa endometrial epithelial cell
      line (PROKR1-Ishikawa). The first aim of the study was to determine the effect of
      PROK1 on CTGF expression in PROKR1-Ishikawa cells and first-trimester decidua
      samples. Secondly, the effect of CTGF on trophoblast-derived HTR-8/SVneo cell
      adhesion and network formation was investigated. METHODS AND RESULTS: Real-time
      qPCR showed that CTGF expression is elevated in first-trimester decidua compared
      with non-pregnant endometrium. In decidua, CTGF co-localized with PROKR1 to the
      glandular epithelium and a subset of stromal cells. PROK1 increased CTGF mRNA and
      protein expression in PROKR1-Ishikawa cells and first-trimester human decidua (8
      12 weeks gestation). Knock down of endogenous PROK1 using micro RNA constructs
      targeted at PROK1, resulted in decreased expression of CTGF mRNA and protein in
      decidua. Inhibitors of specific cell signalling molecules demonstrated that PROK1
      regulates CTGF expression via the Gq, phospholipase C (PLC), cSrc, epidermal
      growth factor receptor (EGFR), mitogen-activated protein kinase/extracellular
      signal-regulated kinase (MAPK/ERK) kinase pathway activation. Treatment of
      trophoblast-derived HTR-8/Svneo cells with 1 ug/ml CTGF significantly increased
      adhesion to collagen IV, and differentiation of the cells into tube-like
      structures in matrigel. CONCLUSIONS: CTGF expression in early pregnancy decidua
      is regulated by PROK1, via activation of the Gq, PLC, cSrc, EGFR, MAPK/ERK kinase
      pathway. CTGF in turn may contribute to the regulation of trophoblast conversion
      of maternal spiral arteries.

PMID- 21098625
TI  - Effect of primary human endometrial stromal cells on epithelial cell receptivity
      and protein expression is dependent on menstrual cycle stage.
AB  - BACKGROUND: Successful implantation requires a receptive endometrium. We
      hypothesized that effects of endometrial stromal cells (ESC) on epithelial cell
      receptivity and trophoblast-endometrium interaction are menstrual cycle
      dependent. METHODS: An endometrial in vitro 3D co-culture model of primary human
      ESC with the endometrial epithelial cell line (RL95-2) was constructed. Co
      cultures were prepared using primary ESC from biopsies taken before the window of
      implantation (ESCbw) and during the window of implantation (ESCw), on cycle days
      10-17 and 19-23, respectively. RL95-2 served as a constant parameter upon which
      the influence of ESC from different phases of the cycle was investigated. proMMP
      2 (MMP, matrix metalloproteinase) and proMMP-9 secretion was tested in response
      to progesterone. Progesterone receptor B (PR-B) and plexin B1 protein expression
      and mRNA levels were investigated using immunofluorescence and RT-PCR,
      respectively. RESULTS: Progesterone increased proMMP-2 secretion in primary ESCbw
      (P = 0.0046) but decreased proMMP-2 and proMMP-9 secretion in ESCw (P < 0.0005).
      In the presence of ESCbw, JAR spheroid attachment rate to overlying RL95-2 cells
      was decreased (P < 0.0001), whereas in the presence of ESCw, attachment rate was
      unchanged. Progesterone treatment restored epithelial cell receptivity in co
      culture with ESCbw (P = 0.00004). A correlation between spheroid attachment rate
      and plexin B1 mRNA level was observed (P = 0.01). PR-B protein and mRNA level
      were influenced by the interplay between RL95-2 and stromal cells. CONCLUSION:
      The effects of human primary ESC on epithelial cell receptivity and trophoblast
      endometrium interaction depended upon whether the ESC were taken before or during
      the window of implantation.

PMID- 21098626
TI  - Assessment of hirsutism among Korean women: results of a randomly selected sample
      of women seeking pre-employment physical check-up.
AB  - BACKGROUND: The objectives of this study were to define the distribution of the
      modified Ferriman-Gallwey (mF-G) score in a random group of Korean women and to
      study any association(s) between hirsutism and endocrine/metabolic markers.
      METHODS: A single investigator assessed the mF-G score prospectively in 1010
      Korean women, who consulted a health-care center as part of a group check-up for
      employment. Logistic regression models were utilized to test the relationships
      between the presence of hirsutism and levels of endocrine/metabolic markers.
      RESULTS: Subjects had mF-G scores ranging from 0 to 19, and 505 subjects (50.0%)
      had an mF-G score of zero. Of the 1010 subjects, 95.1% had a score at or below
      six; thus, a score of six or greater represented hirsute women in our population.
      The most frequently affected site was the upper back, but the most densely
      affected area was found to be the lower abdomen. Hirsutism was significantly and
      positively associated with serum levels of total testosterone (T) and hemoglobin
      A1(c), but negatively associated with those of sex hormone binding globulin
      (SHBG). In addition, the odds of a woman developing hirsutism were higher for
      increased total T and HbA1(c), and lower for decreased SHBG. Hirsutism and
      homeostatic model assessment for insulin resistance were positively associated,
      but the relationship was not significant after adjusting for age and BMI.
      CONCLUSIONS: mF-G scores greater that six represent the appropriate diagnostic
      cutoff for the detection of hirsutism in Korean women. Increased serum total T
      and HbA1(c,) and decreased SHBG concentrations were associated with the presence
      of hirsutism.

PMID- 21098627
TI  - Phenotype and metabolic profile of South Asian women with polycystic ovary
      syndrome (PCOS): results of a large database from a specialist Endocrine Clinic.
AB  - BACKGROUND: Compared with other populations, South Asians have a greater
      propensity to insulin resistance and the metabolic syndrome (MetS). This is the
      first study to determine the distribution of phenotypes of polycystic ovary
      syndrome (PCOS) and their relationship to the MetS among indigenous South Asians.
      METHOD: An evaluation of the phenotype and metabolic characteristics of PCOS was
      conducted by recruiting consecutive women diagnosed by Rotterdam consensus
      criteria from an Endocrine clinic in Colombo, Sri Lanka. Prevalence of MetS was
      determined, in relation to the phenotypic subgroup of PCOS and compared with
      ethnically matched, BMI- and age-adjusted controls (n =231). RESULTS: Acanthosis
      nigricans (AN) occurred in 64.6% of women with PCOS (n= 469). MetS occurred in
      30.6% of the PCOS group compared with 6.34% of controls (P = 0.0001). Those with
      PCOS and MetS had significantly higher median BMI, blood pressure (BP), fasting
      plasma glucose, insulin and triglycerides and lower high-density lipoprotein and
      sex hormone-binding globulin (SHBG), but similar testosterone concentrations
      compared with those with PCOS alone. Prevalence of MetS was similar in the four
      PCOS phenotypes, although oligomenorrhoeic women were more obese compared with
      the normal cycling hyperandrogenic group. Multivariate logistic regression
      confirmed age >=35 years, BMI >=25 kg/m(2) and AN as significant predictors of
      MetS in PCOS. Case-control comparisons showed that the presence of PCOS results
      in higher odds of having the MetS, a high waist circumference, elevated diastolic
      BP, abnormal fasting lipids and high fasting insulin and plasma testosterone
      concentrations. CONCLUSIONS: Young indigenous South Asians with PCOS have greater
      odds of being centrally obese, with a third having the MetS that bears no
      relationship to the androgenic phenotype. Significant predictors for MetS within
      the PCOS cohort are advancing age, obesity determined by the Asian cut off (BMI
      >25 kg/m(2)) and AN, while family history of diabetes, hyperandrogenism and
      elevated SHBG have no predictive value.

PMID- 21098628
TI  - How operating room efficiency is understood in a surgical team: a qualitative
      study.
AB  - OBJECTIVE: Building surgical teams is one attempt to ensure the health-care
      system becomes more efficient, but how is 'efficiency' understood or interpreted?
      The aim was to study how organized surgical team members and their leaders
      understood operating room efficiency. DESIGN: Qualitative study. SETTING: A 1100
      bed Swedish university hospital. PARTICIPANTS: Eleven participants, nine team
      members from the same team and their two leaders were interviewed. METHODS: The
      analysis was performed according to phenomenography, a research approach that
      aims to discover variations in peoples' understanding of a phenomenon. RESULTS:
      Seven ways of understanding operating room efficiency were identified: doing
      one's best from one's prerequisites, enjoying work and adjusting it to the
      situation, interacting group performing parallel tasks, working with minimal
      resources to produce desired results, fast work with preserved quality, long-term
      effects for patient care and a relative concept. When talking about the quality
      and benefits of delivered care, most team members invoked the patient as the
      central focus. Despite seven ways of understanding efficiency between the team
      members, they described their team as efficient. The nurses and assistant nurses
      were involved in the production and discussed working in a timely manner more
      than the leaders. CONCLUSIONS: The seven ways of understanding operating room
      efficiency appear to represent both organization-oriented and individual-oriented
      understanding of that concept in surgical teams. The patient is in focus and
      efficiency is understood as maintaining quality of care and measuring benefits of
      care for the patients.

PMID- 21098629
TI  - IEC standards for individual monitoring of ionising radiation.
AB  - This paper presents IEC/SC 45B 'Radiation protection instrumentation' and its
      standards for individual monitoring of ionising radiation: IEC 61526 Ed. 3 for
      active personal dosemeters and IEC 62387-1 for passive integrating dosimetry
      systems. The transposition of these standards as CENELEC (European) standards is
      also discussed together with the collaboration between IEC/SC 45B and ISO/TC
      85/SC 2.

PMID- 21098630
TI  - A prospective study of the synergistic effects of arsenic exposure and smoking,
      sun exposure, fertilizer use, and pesticide use on risk of premalignant skin
      lesions in Bangladeshi men.
AB  - Skin lesions are classic clinical signs of toxicity due to long-term exposure to
      arsenic, and they are considered precursors to arsenic-related skin cancer. The
      authors prospectively evaluated synergisms between effects of arsenic exposure
      and those of tobacco use, sun exposure, and pesticide and fertilizer use on
      incident skin lesions using risk factor data from 5,042 men from the Health
      Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited
      participants from October 2000 to May 2002. Discrete time hazard models were used
      to estimate measures of synergistic interactions on the additive scale. The
      authors observed significant synergistic effects between various measures of
      arsenic exposure and smoking and fertilizer use. The relative excess risks for
      the interactions between smoking status and arsenic exposure were 0.12 (95%
      confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence
      interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant
      synergistic effects were also observed between fertilizer use and water arsenic
      (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01,
      0.12). This is the first prospective study based on individual-level data that
      supports a role for smoking and certain occupational risk factors in modification
      of the effect of long-term arsenic exposure on skin lesions. Understanding
      differential arsenic susceptibility allows researchers to develop interventions
      to prevent the health consequences of this massive problem in the Bangladeshi
      population and beyond.

PMID- 21098632
TI  - On the interpretation, robustness, and power of varieties of case-only tests of
      gene-environment interaction.
AB  - The author addresses issues related to interpretation of the parameters in the
      proposed case-only linear regression approach to testing for gene-environment
      interaction recently considered by Clarke and Morris (Am J Epidemiol.
      2010;171(4):498-505). He also considers the robustness of their likelihood ratio
      test to violation of the assumption of Gaussian regression residuals under the
      null hypothesis of no interaction; shows how their approach can be extended to a
      more general class of regression models; and derives the optimal interaction test
      statistic for this class of regression models. Finally, the author briefly
      discusses case-only doubly robust methods recently proposed by Tchetgen Tchetgen
      and Robins (Biometrics. 2010;Mar 11).

PMID- 21098631
TI  - Maternal dietary patterns during early pregnancy and the odds of childhood germ
      cell tumors: A Children's Oncology Group study.
AB  - Maternal diet during pregnancy may be associated with cancer in offspring. Intake
      of individual foods, as well as dietary patterns, can be used when examining
      these relations. Here, the authors examined associations between maternal dietary
      intake patterns and pediatric germ cell tumors (GCTs) using principal components
      analysis and logistic regression. Mothers of 222 GCT cases aged less than 15
      years who were diagnosed at a Children's Oncology Group institution between 1993
      and 2001 and those of 336 frequency-matched controls completed a self
      administered food frequency questionnaire of diet during early pregnancy. Four
      dietary patterns were identified: "Western," "fruits and vegetables," "protein,"
      and "healthful." With adjustment for birth weight, parity, and vitamin use, the
      fruits and vegetables pattern was significantly associated with a lower odds for
      GCTs (odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.69, 0.99; 2 sided).
      Upon stratification, the fruits and vegetables pattern was significantly
      associated with a lower odds in males (OR = 0.66, 95% CI: 0.47, 0.92) but not
      females (OR = 0.91, 95% CI: 0.72, 1.14). A quantitative assessment of assumed
      nondifferential reporting error indicated no notable deviations from unadjusted
      odds ratio estimates. Results of this exploratory analysis suggest that maternal
      prenatal dietary patterns could be considered in future studies of GCTs in
      offspring.

PMID- 21098633
TI  - Caveolin limits membrane microdomain mobility and integrin-mediated uptake of
      fibronectin-binding pathogens.
AB  - Staphylococcus aureus, which is a leading cause of hospital-acquired infections,
      binds via fibronectin to integrin alpha5beta1, a process that can promote host
      colonization in vivo. Integrin engagement induces actin cytoskeleton
      rearrangements that result in the uptake of S. aureus by non-professional
      phagocytic cells. Interestingly, we found that fibronectin-binding S. aureus
      trigger the redistribution of membrane microdomain components. In particular,
      ganglioside GM1 and GPI-linked proteins were recruited upon integrin beta1
      engagement, and disruption of membrane microdomains blocked bacterial
      internalization. Several membrane-microdomain-associated proteins, such as
      flotillin-1 and flotillin-2, as well as caveolin, were recruited to sites of
      bacterial attachment. Whereas dominant-negative versions of flotillin-2 did not
      affect bacterial attachment or internalization, cells deficient for caveolin-1
      (Cav1(-/-)) showed increased uptake of S. aureus and other Fn-binding pathogens.
      Recruitment of membrane microdomains to cell-associated bacteria was unaltered in
      Cav1(-/-) cells. However, fluorescence recovery after photobleaching (FRAP)
      revealed an enhanced mobility of membrane-microdomain-associated proteins in the
      absence of caveolin-1. Enhanced membrane microdomain mobility and increased
      uptake of S. aureus was repressed by expression of wild-type caveolin-1, but not
      caveolin-1 G83S, which harbors a point mutation in the caveolin scaffolding
      domain. Similarly, chemical or physical stimulation of membrane fluidity led to
      increased uptake of S. aureus. These results highlight a crucial role for
      caveolin-1 in negative regulation of membrane microdomain mobility, thereby
      affecting endocytosis of bacteria-engaged integrins. This process might not only
      limit host cell invasion by integrin-binding bacterial pathogens, but might also
      be physiologically relevant for integrin-mediated cell adhesion.

PMID- 21098634
TI  - The transporter associated with antigen processing (TAP) is active in a post-ER
      compartment.
AB  - The translocation of cytosolic peptides into the lumen of the endoplasmic
      reticulum (ER) is a crucial step in the presentation of intracellular antigen to
      T cells by major histocompatibility complex (MHC) class I molecules. It is
      mediated by the transporter associated with antigen processing (TAP) protein,
      which binds to peptide-receptive MHC class I molecules to form the MHC class I
      peptide-loading complex (PLC). We investigated whether TAP is present and active
      in compartments downstream of the ER. By fluorescence microscopy, we found that
      TAP is localized to the ERGIC (ER-Golgi intermediate compartment) and the Golgi
      of both fibroblasts and lymphocytes. Using an in vitro vesicle formation assay,
      we show that COPII vesicles, which carry secretory cargo out of the ER, contain
      functional TAP that is associated with MHC class I molecules. Together with our
      previous work on post-ER localization of peptide-receptive class I molecules, our
      results suggest that loading of peptides onto class I molecules in the context of
      the peptide-loading complex can occur outside the ER.

PMID- 21098635
TI  - Mid1p-dependent regulation of the M-G1 transcription wave in fission yeast.
AB  - The control of gene expression at certain times during the mitotic cell division
      cycle is a common feature in eukaryotes. In fission yeast, at least five waves of
      gene expression have been described, with one transcribed at the M-G1 interval
      under the control of the PBF transcription factor complex. PBF consists of at
      least three transcription factors, two forkhead-like proteins Sep1p and Fkh2p,
      and a MADS box-like protein Mbx1p, and binds to PCB motifs found in the gene
      promoters. Mbx1p is under the direct control of the polo-like kinase Plo1p and
      the Cdc14p-like phosphatase Clp1p (Flp1p). Here, we show that M-G1 gene
      expression in fission yeast is also regulated by the anillin-like protein, Mid1p
      (Dmf1p). Mid1p binds in vivo to both Fkh2p and Sep1p, and to the promoter regions
      of M-G1 transcribed genes. Mid1p promoter binding is dependent on Fkh2p, Plo1p
      and Clp1p. The absence of mid1(+) in cells results in partial loss of M-G1
      specific gene expression, suggesting that it has a negative role in controlling
      gene expression. This phenotype is exacerbated by also removing clp1(+),
      suggesting that Mid1p and Clp1p have overlapping functions in controlling
      transcription. As mid1(+) is itself expressed at M-G1, these observations offer a
      new mechanism whereby Mid1p contributes to controlling cell cycle-specific gene
      expression as part of a feedback loop.

PMID- 21098637
TI  - S-RNase disrupts tip-localized reactive oxygen species and induces nuclear DNA
      degradation in incompatible pollen tubes of Pyrus pyrifolia.
AB  - Pear (Pyrus pyrifolia L.) has an S-RNase-based gametophytic self-incompatibility
      (SI) mechanism, and S-RNase has also been implicated in the rejection of self
      pollen and genetically identical pollen. However, RNA degradation might be only
      the beginning of the SI response, not the end. Recent in vitro studies suggest
      that S-RNase triggers mitochondrial alteration and DNA degradation in the
      incompatible pollen tube of Pyrus pyrifolia, and it seems that a relationship
      exists between self S-RNase, actin depolymerization and DNA degradation. To
      further uncover the SI response in pear, the relationship between self S-RNase
      and tip-localized reactive oxygen species (ROS) was evaluated. Our results show
      that S-RNase specifically disrupted tip-localized ROS of incompatible pollen
      tubes via arrest of ROS formation in mitochondria and cell walls. The
      mitochondrial ROS disruption was related to mitochondrial alteration, whereas
      cell wall ROS disruption was related to a decrease in NADPH. Tip-localized ROS
      disruption not only decreased the Ca(2+) current and depolymerized the actin
      cytoskeleton, but it also induced nuclear DNA degradation. These results indicate
      that tip-localized ROS disruption occurs in Pyrus pyrifolia SI. Importantly, we
      demonstrated nuclear DNA degradation in the incompatible pollen tube after
      pollination in vivo. This result validates our in vitro system in vivo.

PMID- 21098636
TI  - Shared molecular mechanisms regulate multiple catenin proteins: canonical Wnt
      signals and components modulate p120-catenin isoform-1 and additional p120
      subfamily members.
AB  - Wnt signaling pathways have fundamental roles in animal development and tumor
      progression. Here, employing Xenopus embryos and mammalian cell lines, we report
      that the degradation machinery of the canonical Wnt pathway modulates p120
      catenin protein stability through mechanisms shared with those regulating beta
      catenin. For example, in common with beta-catenin, exogenous expression of
      destruction complex components, such as GSK3beta and axin, promotes degradation
      of p120-catenin. Again in parallel with beta-catenin, reduction of canonical Wnt
      signals upon depletion of LRP5 and LRP6 results in p120-catenin degradation. At
      the primary sequence level, we resolved conserved GSK3beta phosphorylation sites
      in the amino-terminal region of p120-catenin present exclusively in isoform-1.
      Point-mutagenesis of these residues inhibited the association of destruction
      complex components, such as those involved in ubiquitylation, resulting in
      stabilization of p120-catenin. Functionally, in line with predictions, p120
      stabilization increased its signaling activity in the context of the p120-Kaiso
      pathway. Importantly, we found that two additional p120-catenin family members,
      ARVCF-catenin and delta-catenin, associate with axin and are degraded in its
      presence. Thus, as supported using gain- and loss-of-function approaches in
      embryo and cell line systems, canonical Wnt signals appear poised to have an
      impact upon a breadth of catenin biology in vertebrate development and, possibly,
      human cancers.

PMID- 21098638
TI  - Quantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders
      suggests a correlation between phenotypic severity and Smad signaling activity.
AB  - Mutations in the gene encoding transforming growth factor-beta receptor type II
      (TGFBR2) have been described in patients with Loeys-Dietz syndrome (LDS), Marfan
      syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections
      (TAAD). Here, we present a comprehensive and quantitative analysis of TGFBR2
      expression, turnover and TGF-beta-induced Smad and ERK signaling activity for
      nine mutations identified in patients with LDS, MFS2 and TAAD. The mutations had
      different effects on protein stability, internalization and signaling. A dominant
      negative effect was demonstrated for mutations associated with LDS and MFS2. No
      mutation showed evidence of an immediate cell-autonomous paradoxical activation
      of TGF-beta signaling. There were no cell biological differences between
      mutations described in patients with LDS and MFS2. By contrast, R460C, which has
      been found in familial TAAD but not in MFS2 or LDS, showed a less-severe dominant
      negative effect and retained residual Smad phosphorylation and transcriptional
      activity. TAAD is characterized primarily by thoracic aortic aneurysms or
      dissections. By contrast, MFS2 is characterized by numerous skeletal
      abnormalities, and patients with LDS additionally can display craniofacial and
      other abnormalities. Therefore, our findings suggest that the balance between
      defects in Smad and ERK signaling might be an important determinant of phenotypic
      severity in disorders related to mutations in TGFBR2.

PMID- 21098639
TI  - Serine 363 of the {delta}-opioid receptor is crucial for adopting distinct
      pathways to activate ERK1/2 in response to stimulation with different ligands.
AB  - Distinct opioid receptor agonists have been proved to induce differential
      patterns of ERK activation, but the underlying mechanisms remain unclear. Here,
      we report that Ser363 in the delta-opioid receptor (deltaOR) determines the
      different abilities of the deltaOR agonists DPDPE and TIPP to activate ERK by G
      protein- or beta-arrestin-dependent pathways. Although both DPDPE and TIPP
      activated ERK1/2, they showed different temporal, spatial and desensitization
      patterns of ERK activation. We show that that DPDPE employed G protein as the
      primary mediator to activate the ERK cascade in an Src-dependent manner, whereas
      TIPP mainly adopted a beta-arrestin1/2-mediated pathway. Moreover, we found that
      DPDPE gained the capacity to adopt the beta-arrestin1/2-mediated pathway upon
      Ser363 mutation, accompanied by the same pattern of ERK activation as that
      induced by TIPP. Additionally, we found that TIPP- but not DPDPE-activated ERK
      could phosphorylate G-protein-coupled receptor kinase-2 and beta-arrestin1.
      However, such functional differences of ERK disappeared with the mutation of
      Ser363. Therefore, the present study reveals a crucial role for Ser363 in agonist
      specific regulation of ERK activation patterns and functions.

PMID- 21098641
TI  - Regulation of cell cycle-specific gene expression in fission yeast by the Cdc14p
      like phosphatase Clp1p.
AB  - Regulated gene expression makes an important contribution to cell cycle control
      mechanisms. In fission yeast, a group of genes is coordinately expressed during a
      late stage of the cell cycle (M phase and cytokinesis) that is controlled by
      common cis-acting promoter motifs named pombe cell cycle boxes (PCBs), which are
      bound by a trans-acting transcription factor complex, PCB binding factor (PBF).
      PBF contains at least three transcription factors, a MADS box protein Mbx1p and
      two forkhead transcription factors, Sep1p and Fkh2p. Here we show that the
      fission yeast Cdc14p-like phosphatase Clp1p (Flp1p) controls M-G1 specific gene
      expression through PBF. Clp1p binds in vivo both to Mbx1p, a MADS box-like
      transcription factor, and to the promoters of genes transcribed at this cell
      cycle time. Because Clp1p dephosphorylates Mbx1p in vitro, and is required for
      Mbx1p cell cycle-specific dephosphorylation in vivo, our observations suggest
      that Clp1p controls cell cycle-specific gene expression through binding to and
      dephosphorylating Mbx1p.

PMID- 21098640
TI  - p38 maintains E-cadherin expression by modulating TAK1-NF-kappa B during
      epithelial-to-mesenchymal transition.
AB  - Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells is a
      pathological process that occurs during peritoneal dialysis. EMT leads to
      peritoneal fibrosis, ultrafiltration failure and eventually to the
      discontinuation of therapy. Signaling pathways involved in mesothelial EMT are
      thus of great interest, but are mostly unknown. We used primary mesothelial cells
      from human omentum to analyze the role of the p38 MAPK signaling pathway in the
      induction of EMT. The use of specific inhibitors, a dominant-negative p38 mutant
      and lentiviral silencing of p38alpha demonstrated that p38 promotes E-cadherin
      expression both in untreated cells and in cells co-stimulated with the EMT
      inducing stimuli transforming growth factor (TGF)-beta1 and interleukin (IL)
      1beta. p38 inhibition also led to disorganization and downregulation of
      cytokeratin filaments and zonula occludens (ZO)-1, whereas expression of vimentin
      was increased. Analysis of transcription factors that repress E-cadherin
      expression showed that p38 blockade inhibited expression of Snail1 while
      increasing expression of Twist. Nuclear translocation and transcriptional
      activity of p65 NF-kappaB, an important inducer of EMT, was increased by p38
      inhibition. Moreover, p38 inhibition increased the phosphorylation of TGF-beta
      activated kinase 1 (TAK1), NF-kappaB and IkappaBalpha. The effect of p38
      inhibition on E-cadherin expression was rescued by modulating the TAK1-NF-kappaB
      pathway. Our results demonstrate that p38 maintains E-cadherin expression by
      suppressing TAK1-NF-kappaB signaling, thus impeding the induction of EMT in human
      primary mesothelial cells. This represents a novel role of p38 as a brake or
      'gatekeeper' of EMT induction by maintaining E-cadherin levels.

PMID- 21098642
TI  - RAGE-TXNIP axis is required for S100B-promoted Schwann cell migration,
      fibronectin expression and cytokine secretion.
AB  - During peripheral nerve injury, Schwann cells (SCs) adopt a migratory phenotype
      and remodel the extracellular matrix and provide a supportive activity for neuron
      regeneration. SCs synthesize neurotrophic factors and cytokines that are crucial
      for the repair of the injured nerve. The receptor for advanced glycation end
      products (RAGE) and its ligand S100B, which are secreted by SCs, are required for
      the repair of the injured peripheral nerve in vivo. However, the precise
      intracellular pathways involved have not been completely elucidated. Here, we
      show that RAGE-induced S100B secretion involves the recruitment of S100B in lipid
      rafts and caveolae. Moreover, we demonstrate for the first time that RAGE induces
      the expression of thioredoxin interacting protein (TXNIP) in SCs and the injured
      sciatic nerve in vivo. TXNIP is involved in the activation of p38 MAPK, CREB and
      NFkappaB in SCs. TXNIP silencing partially inhibits RAGE-induced SC migration and
      completely abolishes RAGE-induced fibronectin and IL-1beta expression. Our
      results support a model in which TXNIP mediates in part RAGE-induced SC migration
      and is required for the expression of provisional ECM and pro-inflammatory IL
      1beta. We provide new insight on the role of the SC RAGE-TXNIP axis in the repair
      of injured peripheral nerves.

PMID- 21098644
TI  - Prediction of oral pharmacokinetics of cMet kinase inhibitors in humans:
      physiologically based pharmacokinetic model versus traditional one-compartment
      model.
AB  - The objective of this study was to assess the physiologically based
      pharmacokinetic (PBPK) model for predicting plasma concentration-time profiles of
      orally available cMet kinase inhibitors, (R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)
      ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine (PF02341066) and 2
      [4-(3-quinolin-6-ylmethyl-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl)-pyrazol-1-yl]
      ethanol (PF04217903), in humans. The prediction accuracy of pharmacokinetics (PK)
      by PBPK modeling was compared with that of a traditional one-compartment PK model
      based on allometric scaling. The predicted clearance values from allometric
      scaling with the correction for the interspecies differences in protein binding
      were used as a representative comparison, which showed more accurate PK
      prediction in humans than the other methods. Overall PBPK modeling provided
      better prediction of the area under the plasma concentration-time curves for both
      PF02341066 (1.2-fold error) and PF04217903 (1.3-fold error) compared with the one
      compartment PK model (1.8- and 1.9-fold errors, respectively). Of more
      importance, the simulated plasma concentration-time profiles of PF02341066 and
      PF04217903 by PBPK modeling seemed to be consistent with the observed profiles
      showing multiexponential declines, resulting in more accurate prediction of the
      apparent half-lives (t(1/2)): the observed and predicted t(1/2) values were,
      respectively, 10 and 12 h for PF02341066 and 6.6 and 6.3 h for PF04217903. The
      predicted t(1/2) values by the one-compartment PK model were 17 h for PF02341066
      and 1.9 h for PF04217903. Therefore, PBPK modeling has the potential to be more
      useful and reliable for the PK prediction of PF02341066 and PF04217903 in humans
      than the traditional one-compartment PK model. In summary, the present study has
      shown examples to indicate that the PBPK model can be used to predict PK profiles
      in humans.

PMID- 21098643
TI  - Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa
      that can dramatically increase the risk of colon cancers. In the present study,
      we evaluated the effects of a dietary intervention of freeze-dried black
      raspberries (BRB), a natural food product with antioxidant and anti-inflammatory
      bioactivities, on disease severity in an experimental mouse model of UC using 3%
      dextran sodium sulfate (DSS). C57BL/6J mice were fed either a control diet or a
      diet containing BRB (5 or 10%) for 7-14 days and then the extent of colonic
      injury was assessed. Dietary BRB markedly reduced DSS-induced acute injury to the
      colonic epithelium. This protection included better maintenance of body mass and
      reductions in colonic shortening and ulceration. BRB treatment, however, did not
      affect the levels of either plasma nitric oxide or colon malondialdehyde,
      biomarkers of oxidative stress that are otherwise increased by DSS-induced
      colonic injury. BRB treatment for up to 7 days suppressed tissue levels of
      several key pro-inflammatory cytokines, including tumor necrosis factor alpha and
      interleukin 1beta. Further examination of the inflammatory response by western
      blot analysis revealed that 7 day BRB treatment reduced the levels of phospho
      IkappaBalpha within the colonic tissue. Colonic cyclooxygenase 2 levels were also
      dramatically suppressed by BRB treatment, with a concomitant decrease in the
      plasma prostaglandin E2 (276 versus 34 ng/ml). These findings demonstrate a
      potent anti-inflammatory effect of BRB during DSS-induced colonic injury,
      supporting its possible therapeutic or preventive role in the pathogenesis of UC
      and related neoplastic events.

PMID- 21098645
TI  - Effects of cell differentiation and assay conditions on the UDP
      glucuronosyltransferase activity in Caco-2 cells.
AB  - Cell differentiation increases UDP-glucuronosyltransferase (UGT) gene expression
      in Caco-2 cells. Glucuronidation of 13 UGT substrates, 1-naphthol, diclofenac,
      epitestosterone, estradiol, ethinylestradiol, indomethacin, oxazepam, R- and S
      propranolol, propofol, testosterone, trifluoperazine, and zidovudine, were
      studied to derive a broad view on the effect of cell differentiation on the
      glucuronidation activities of different human UGTs. In parallel, the
      glucuronidation of these compounds in human liver microsomes (HLM) and human
      intestinal microsomes (HIM) was analyzed. Because many of the substrates are
      highly lipophilic, the effects of dimethyl sulfoxide (DMSO) concentrations in the
      reaction mixture on glucuronidation rates were tested, as well as the effect of
      alamethicin, a pore-forming peptide. Large differences were observed in the
      effects of DMSO and alamethicin between recombinant UGTs and Caco-2 cells and HLM
      and HIM, and, therefore, the activity assays were performed under multiple
      conditions. Regardless of the assay conditions, however, the results clearly
      indicated that although differentiation increases glucuronidation activity, the
      rates in Caco-2 cells are mostly very low, much lower than those in either HLM or
      HIM. One clear exception was observed: substrates of UGT1A6, such as 1-naphthol,
      were glucuronidated at very high rates in both undifferentiated and
      differentiated Caco-2 cells. It may thus be concluded that Caco-2 cells, even
      differentiated ones, do not provide a good model system to assess first-pass drug
      glucuronidation in the intestine.

PMID- 21098647
TI  - Control and measurement of plasma pH in equilibrium dialysis: influence on drug
      plasma protein binding.
AB  - Past publications have highlighted the influence of postdialysis plasma pH on the
      measured fraction unbound in plasma (fup). There is disparity in the industry as
      to which of two main methods is more suitable for controlling postdialysis plasma
      pH: the use of either a stronger buffer or a CO(2) atmosphere for the incubation.
      In the current study, it has been found that 10% CO(2) could be too high for the
      buffering capacities of both 100 mM sodium phosphate (pH 7.40 decreased to pH
      6.90 after a 6-h incubation) and plasma (decreased below pH 7.40 after a 6-h
      incubation). To provide appropriate control over the postdialysis plasma pH, for
      a range of species, it is proposed that a standard phosphate buffer strength (100
      mM) and pH (7.40) in combination with a 5% CO(2) atmosphere be used for
      equilibrium dialysis. Furthermore, statistically significant differences in fup
      values obtained with a pH difference of less than 0.32 pH unit have been
      demonstrated. An acceptance range for postdialysis plasma pH in routine in vitro
      fup screening assays of pH 7.40 +/- 0.10 is recommended.

PMID- 21098646
TI  - Disposition and metabolism of cumene in F344 rats and B6C3F1 mice.
AB  - Cumene is a high-production volume chemical that has been shown to be a central
      nervous system depressant and has been implicated as a long-term exposure
      carcinogen in experimental animals. The absorption, distribution, metabolism, and
      excretion of [(14)C]cumene (isopropylbenzene) was studied in male rats and mice
      of both sexes after oral or intravenous administration. In both species and
      sexes, urine accounted for the majority of the excretion (typically >= 70%) by
      oral and intravenous administration. Enterohepatic circulation of cumene and/or
      its metabolites was indicated because 37% of the total dose was excreted in bile
      in bile duct-cannulated rats with little excreted in normal rats. The highest
      tissue (14)C levels in rats were observed in adipose tissue, liver, and kidney
      with no accumulation observed after repeat dosing up to 7 days. In contrast, mice
      contained the highest concentrations of (14)C at 24 h after dosing in the liver,
      kidney, and lung, with repeat dosing accumulation of (14)C observed in these
      tissues as well as in the blood, brain, heart, muscle, and spleen. The
      metabolites in the expired air, urine, bile, and microsomes were characterized
      with 16 metabolites identified. The volatile organics in the expired air
      comprised mainly cumene and up to 4% alpha-methylstyrene. The major urinary and
      biliary metabolite was 2-phenyl-2-propanol glucuronide, which corresponded with
      the main microsomal metabolite being 2-phenyl-2-propanol.

PMID- 21098648
TI  - Dietary phytoestrogens and the risk of ovarian cancer in the women's lifestyle
      and health cohort study.
AB  - BACKGROUND: Dietary intake of phytoestrogens has been inversely associated to
      hormone-dependent cancers, such as prostate and breast cancers. Few studies have
      investigated the association between ovarian cancer and intake of phytoestrogens.
      We evaluated the associations between intake of phytoestrogens
      (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of
      ovarian cancer. METHODS: In 1991-1992 a prospective population-based cohort study
      among Swedish women was conducted, including 47,140 women with complete dietary
      questionnaire data. During follow-up until December 2007, 163 women developed
      invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up
      time was 16 years and total person year was 747,178. Cox proportional hazards
      models were conducted to estimate multivariate risk ratios, 95% CI for
      associations with risk of ovarian cancer. RESULTS: We found no association
      between intake of phytoestrogens or fiber and overall ovarian cancer risk. In
      addition, we found no statistically significant association between intake of
      specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp
      or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was
      inversely associated with borderline ovarian cancer, but not with invasive
      ovarian cancer. CONCLUSIONS: We found no association between intake of
      phytoestrogens or fiber and overall ovarian cancer risk. IMPACT: Phytoestrogens
      do not play a major etiologic role in ovarian cancer, at least among women in
      this Swedish cohort with low bean/soy intake. However, our results of a
      difference in the effect of fiber or coumestrol between invasive and borderline
      ovarian cancer need to be evaluated in larger studies.

PMID- 21098649
TI  - Feasibility of identifying pancreatic cancer based on serum metabolomics.
AB  - BACKGROUND: We postulated that the abundance of various metabolites in blood
      would facilitate the diagnosis of pancreatic and biliary lesions, which could
      potentially prevent unnecessary surgery. METHODS: Serum samples from patients
      with benign hepatobiliary disease (n = 43) and from patients with pancreatic
      cancer (n = 56) were examined by 1H NMR spectroscopy to quantify 58 unique
      metabolites. Data were analyzed by "targeted profiling" followed by supervised
      pattern recognition and orthogonal partial least-squares discriminant analysis (O
      PLS-DA) of the most significant metabolites, which enables comparison of the
      whole sample spectrum between groups. RESULTS: The metabolomic profile of
      patients with pancreatic cancer was significantly different from that of patients
      with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes
      mellitus (DM) was identified as a possible confounding factor in the pancreatic
      cancer group. Thus, diabetics were excluded from further analysis. In this more
      homogeneous pancreatic cancer group, compared with benign cases, serum
      concentrations of glutamate and glucose were most elevated on multivariate
      analysis. In benign cases, creatine and glutamine were most abundant. To examine
      the usefulness of this test, a comparison was made to age- and gender-matched
      controls with benign lesions that mimic cancer, controlling also for presence of
      jaundice and diabetes (n = 14 per group). The metabolic profile in patients with
      pancreatic cancer remained distinguishable from patients with benign pancreatic
      lesions (AUROC = 0.8308). CONCLUSIONS: The serum metabolomic profile may be
      useful for distinguishing benign from malignant pancreatic lesions. IMPACT:
      Further studies will be required to study the effects of jaundice and diabetes. A
      more comprehensive metabolomic profile will be evaluated using mass spectrometry.

PMID- 21098650
TI  - Epigenetic deregulation across chromosome 2q14.2 differentiates normal from
      prostate cancer and provides a regional panel of novel DNA methylation cancer
      biomarkers.
AB  - BACKGROUND: Previously, we showed that gene suppression commonly occurs across
      chromosome 2q14.2 in colorectal cancer, through a process of long-range
      epigenetic silencing (LRES), involving a combination of DNA methylation and
      repressive histone modifications. We now investigate whether LRES also occurs in
      prostate cancer across this 4-Mb region and whether differential DNA methylation
      of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers.
      METHODS: We used highly sensitive DNA methylation headloop PCR assays that can
      detect 10 to 25 pg of methylated DNA with a specificity of at least 1:1,000, and
      chromatin immunoprecipitation assays to investigate regional epigenetic
      remodeling across 2q14.2 in prostate cancer, in a cohort of 195 primary prostate
      tumors and 90 matched normal controls. RESULTS: Prostate cancer cells exhibit
      concordant deacetylation and methylation of histone H3 Lysine 9 (H3K9Ac and
      H3K9me2, respectively), and localized DNA hypermethylation of EN1, SCTR, and
      INHBB and corresponding loss of H3K27me3. EN1 and SCTR were frequently methylated
      (65% and 53%, respectively), whereas INHBB was less frequently methylated.
      CONCLUSIONS: Consistent with LRES in colorectal cancer, we found regional
      epigenetic remodeling across 2q14.2 in prostate cancer. Concordant methylation of
      EN1 and SCTR was able to differentiate cancer from normal (P < 0.0001) and
      improved the diagnostic specificity of GSTP1 methylation for prostate cancer
      detection by 26%. IMPACT: For the first time we show that DNA methylation of EN1
      and SCTR promoters provide potential novel biomarkers for prostate cancer
      detection and in combination with GSTP1 methylation can add increased specificity
      and sensitivity to improve diagnostic potential.

PMID- 21098651
TI  - Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the
      European Prospective Investigation into Cancer and Nutrition (EPIC).
AB  - BACKGROUND: Case-control studies suggested a moderate, but consistent,
      association of hepatitis C virus (HCV) infection with lymphoid tissue
      malignancies, especially non-Hodgkin lymphoma (NHL). More limited data suggested
      that hepatitis B virus (HBV) infection might also be associated with NHL.
      However, prospective studies on the topic are few. METHODS: A nested case-control
      study was conducted in eight countries participating in the EPIC prospective
      study. Seven hundred thirty-nine incident cases of NHL, 238 multiple myeloma
      (MM), and 46 Hodgkin lymphoma (HL) were matched with 2,028 controls.
      Seropositivity to anti-HCV, anti-HBc, and HBsAg was evaluated and conditional
      logistic regression was used to estimate odds ratios (OR) and corresponding 95%
      confidence intervals (CI) for NHL, MM, or HL, and their combination. RESULTS:
      Anti-HCV seropositivity among controls in different countries ranged from 0% to
      5.3%; HBsAg from 0% to 2.7%; and anti-HBc from 1.9% to 45.9%. Similar
      nonsignificant associations were found with seropositivity to HBsAg for NHL (OR =
      1.78; 95% CI: 0.78-4.04), MM (OR = 4.00; 95% CI: 1.00-16.0), and HL (OR = 2.00;
      95% CI: 0.13-32.0). The association between HBsAg and the combination of NHL, MM,
      and HL (OR = 2.21; 95% CI: 1.12-4.33) was similar for cancer diagnosed less than
      3 and 3 or more years after blood collection. No significant association was
      found between anti-HCV and NHL, MM, or HL risk, but the corresponding CIs were
      very broad. CONCLUSIONS: Chronic HBV infection may increase the risk of lymphoid
      malignancies among healthy European volunteers. IMPACT: Treatment directed at
      control of HBV infection should be evaluated in HBsAg-seropositive patients with
      lymphoid tissue malignancies.

PMID- 21098652
TI  - Identification of a tertiary interaction important for cooperative ligand binding
      by the glycine riboswitch.
AB  - The glycine riboswitch has a tandem dual aptamer configuration, where each
      aptamer is a separate ligand-binding domain, but the aptamers function together
      to bind glycine cooperatively. We sought to understand the molecular basis of
      glycine riboswitch cooperativity by comparing sites of tertiary contacts in a
      series of cooperative and noncooperative glycine riboswitch mutants using
      hydroxyl radical footprinting, in-line probing, and native gel-shift studies. The
      results illustrate the importance of a direct or indirect interaction between the
      P3b hairpin of aptamer 2 and the P1 helix of aptamer 1 in cooperative glycine
      binding. Furthermore, our data support a model in which glycine binding is
      sequential; where the binding of glycine to the second aptamer allows tertiary
      interactions to be made that facilitate binding of a second glycine molecule to
      the first aptamer. These results provide insight into cooperative ligand binding
      in RNA macromolecules.

PMID- 21098653
TI  - Development of a quantitative RT-PCR assay to examine the kinetics of ribosome
      depurination by ribosome inactivating proteins using Saccharomyces cerevisiae as
      a model.
AB  - Ricin produced by the castor bean plant and Shiga toxins produced by pathogenic
      Escherichia coli (STEC) and Shigella dysenteriae are type II ribosome
      inactivating proteins (RIPs), containing an enzymatically active A subunit that
      inhibits protein synthesis by removing an adenine from the alpha-sarcin/ricin
      loop (SRL) of the 28S rRNA. There are currently no known antidotes to Shiga toxin
      or ricin, and the ability to screen large chemical libraries for inhibitors has
      been hindered by lack of quantitative assays for catalytic activity that can be
      adapted to a high throughput format. Here, we describe the development of a
      robust and quantitative reverse transcription polymerase chain reaction (qRT-PCR)
      assay that can directly measure the toxins' catalytic activity on ribosomes and
      can be used to examine the kinetics of depurination in vivo. The qRT-PCR assay
      exhibited a much wider dynamic range than the previously used primer extension
      assay (500-fold vs. 16-fold) and increased sensitivity (60 pM vs. 0.57 nM). Using
      this assay, a 400-fold increase in ribosome depurination was observed in yeast
      expressing ricin A chain (RTA) relative to uninduced cells. Pteroic acid, a known
      inhibitor of enzymatic activity, inhibited ribosome depurination by RTA and Shiga
      toxin 2 with an IC(50) of ~ 100 MUM, while inhibitors of ricin transport failed
      to inhibit catalytic activity. These results demonstrate that the qRT-PCR assay
      would enable refined kinetic studies with RIPs and could be a powerful screening
      tool to identify inhibitors of catalytic activity.

PMID- 21098655
TI  - Fairness: in the eye of the beholder.

PMID- 21098654
TI  - Transcriptome analysis of embryonic and adult sensory axons reveals changes in
      mRNA repertoire localization.
AB  - mRNAs are transported, localized, and translated in axons of sensory neurons.
      However, little is known about the full repertoire of transcripts present in
      embryonic and adult sensory axons and how this pool of mRNAs dynamically changes
      during development. Here, we used a compartmentalized chamber to isolate mRNA
      from pure embryonic and adult sensory axons devoid of non-neuronal or cell body
      contamination. Genome-wide microarray analysis reveals that a previously
      unappreciated number of transcripts are localized in sensory axons and that this
      repertoire changes during development toward adulthood. Embryonic axons are
      enriched in transcripts encoding cytoskeletal-related proteins with a role in
      axonal outgrowth. Surprisingly, adult axons are enriched in mRNAs encoding immune
      molecules with a role in nociception. Additionally, we show Tubulin-beta3 (Tubb3)
      mRNA is present only in embryonic axons, with Tubb3 locally synthesized in axons
      of embryonic, but not adult neurons where it is transported, thus validating our
      experimental approach. In summary, we provide the first complete catalog of
      embryonic and adult sensory axonal mRNAs. In addition we show that this pool of
      axonal mRNAs dynamically changes during development. These data provide an
      important resource for studies on the role of local protein synthesis in axon
      regeneration and nociception during neuronal development.

PMID- 21098656
TI  - Role of lean body mass in estimating glomerular filtration rate in Alzheimer
      disease.
AB  - BACKGROUND: The association between estimated glomerular filtration rate (eGFR)
      and progression of Alzheimer disease (AD), as measured by cognitive decline and
      brain atrophy, has been infrequently studied. Since AD is characterized by
      sarcopenia and other changes in body composition, which are known to influence
      GFR, a determination of how lean mass (LM) affects estimation of GFR in AD
      patients is important. METHODS: Participants were drawn from a prospective
      longitudinal study of brain ageing and AD in community-dwelling individuals.
      Control (n = 60) and AD (n = 61) participants were enrolled. Estimated GFR was
      calculated using the four-variable Modification of Diet in Renal Disease (MDRD),
      Cockroft-Gault, Macdonald appendicular LM and Taylor LM equations. Association of
      eGFR with 2-year change in cognitive function and brain volume was assessed.
      RESULTS: Individuals with AD demonstrated a paradoxical finding in which lower
      baseline MDRD eGFR was associated with less cognitive decline (P = 0.04) and
      brain atrophy (P = 0.02), a phenomenon not observed in non-AD controls. This
      finding was abolished in the AD patients when either the Macdonald appendicular
      LM or Taylor LM equations were used. While significant group-by-eGFR interactions
      were present for cognitive decline (P = 0.006) and brain atrophy (P = 0.001) when
      the MDRD equation was used, no group-by-eGFR interactions were present when
      either the Macdonald LM (P = 0.58 and P = 0.10 for cognitive decline and brain
      atrophy, respectively) or Taylor LM (P = 0.97 and P = 0.55) equations were used.
      CONCLUSIONS: Accounting for measures of LM in GFR estimation appears to
      significantly mitigate counterintuitive relationships between measures of AD
      progression and eGFR as calculated by more traditional measures of renal
      function. This suggests that consideration of LM in eGFR calculations may be
      important in patients with sarcopenia, such as the AD population.

PMID- 21098657
TI  - Glycated haemoglobin and the incidence of end-stage renal disease in diabetics.
AB  - BACKGROUND: The relationship between glycated haemoglobin and the incidence of
      end-stage renal disease (ESRD) in patients with diabetes remains uncertain,
      especially in those with decreased glomerular filtration rate (GFR). The aim of
      this study was to assess the appropriate HbA(1c) level for diabetics for
      minimizing the incidence of ESRD and all-cause mortality. METHODS: A cohort of
      patients aged 25 years or older who had been treated for diabetes was generated
      from the Seoul National University Bundang Hospital database using diagnosis code
      and prescribed medication during 2004. The 4474 patients were classified into
      three groups according to the baseline HbA(1c) in 2004 (HbA(1c) < 6.50%, 6.50
      7.49% and >= 7.50%; termed groups 1, 2 and 3, respectively). The outcomes were
      extracted from the database of Statistics Korea for mortality and registry in the
      Korean Society of Nephrology for ESRD incidence. RESULTS: Ninety patients
      developed ESRD during 5.29 +/- 1.22 years of mean follow-up period. Group 1
      patients showed the lowest incidence of ESRD (P = 0.003). Compared with this
      group, the adjusted hazard ratio of ESRD was 2.915 and 4.219 in groups 2 and 3,
      respectively. The incidence of ESRD increased in patients with HbA(1c) >= 6.50%
      compared with the patients with HbA(1c) < 6.50%, regardless of GFR. However,
      HbA(1c) < 6.50% showed no benefit on ESRD development in patients older than 80
      years and in patients with diabetic duration > 10 years. All-cause mortality was
      not associated with the level of HbA(1c). CONCLUSIONS: HbA(1c) < 6.50% was
      associated with reduced development of ESRD in all patients and later stages of
      chronic kidney disease.

PMID- 21098658
TI  - Postprandial metabolic response to a fat- and carbohydrate-rich meal in patients
      with chronic kidney disease.
AB  - BACKGROUND: While chronic kidney disease (CKD) is associated with dysmetabolism
      including a marked insulin resistance, the postprandial response has not
      comprehensively been studied in CKD patients. METHODS: We conducted an
      intervention study comparing fasting and postprandial circulating biomarkers of
      glucose and lipid homeostasis, incretins, anabolic hormones, inflammation and
      oxidative stress in nine prevalent non-diabetic hemodialysis (HD) patients and 10
      matched controls assessed after a standardized meal consisting of 75 g of milk
      fat, 80 g of carbohydrates and 6 g of proteins/m(2) of body surface area.
      RESULTS: Glucose and triglyceride increased in a similar manner following the
      meal, while insulin, C-peptide and glucose-dependent insulinotropic polypeptide
      increased more in HD patients. HDL and LDL cholesterol decreased slightly with no
      significant difference between the groups. The elevated baseline growth hormone
      (GH) in patients dropped, resulting in comparable levels in both groups 240 min
      after the meal; however, there was no change in insulin-like growth factor 1 (IGF
      1) levels. No marked changes of interleukin 6 and tumor necrosis factor-alpha
      were observed in either group. An elevation in the DNA oxidative product 8
      hydroxydeoxyguanosine was observed in HD patients. CONCLUSIONS: The postprandial
      state in CKD is characterized by impaired insulin sensitivity with increased
      incretin levels, along with GH/IGF-1 axis uncoupling and an elevation in an
      oxidative stress marker.

PMID- 21098659
TI  - Moral behavior is not what it seems.

PMID- 21098660
TI  - Improved probability of detection of ecological "surprises".
AB  - Ecological "surprises" are defined as unexpected findings about the natural
      environment. They are critically important in ecology because they are catalysts
      for questioning and reformulating views of the natural world, help shape
      assessments of the veracity of a priori predictions about ecological trends and
      phenomena, and underpin questioning of effectiveness of resource management.
      Despite the importance of ecological surprises, major gaps in understanding
      remain about how studies might be done differently or done better to improve the
      ability to identify them. We outline the kinds of ecological surprises that have
      arisen from long-term research programs that we lead in markedly different
      ecosystems around the world. Based on these case studies, we identify important
      lessons to guide both existing studies and new investigations to detect
      ecological surprises more readily, better anticipate unusual ecological
      phenomena, and take proactive steps to plan for and alleviate "undesirable"
      ecological surprises. Some of these lessons include: (i) maintain existing, and
      instigate new, long-term studies; (ii) conduct a range of kinds of parallel and
      concurrent research in a given target area; (iii) better use past literature and
      conceptual models of the target ecosystem in posing good questions and developing
      hypotheses and alternative hypotheses; and (iv) increase the capacity for
      ecological research to take advantage of opportunities arising from major natural
      disturbances. We argue that the increased anticipatory capability resulting from
      these lessons is critical given that ecological surprises may become more
      prevalent because of climate change and multiple and interacting environmental
      stressors.

PMID- 21098662
TI  - Caveolin-1 knockout mice exhibit impaired induction of mGluR-dependent long-term
      depression at CA3-CA1 synapses.
AB  - Group I metabotropic glutamate receptors (mGluR1/5) are important to synaptic
      circuitry formation during development and to forms of activity-dependent
      synaptic plasticity. Dysregulation of mGluR1/5 signaling is implicated in some
      disorders of neurodevelopment, including fragile X syndrome, the most common
      inherited form of intellectual disabilities and leading cause of autism. Site(s)
      in the intracellular loops of mGluR1/5 directly bind caveolin-1, an adaptor
      protein that associates with membrane rafts. Caveolin-1 is the main coat
      component of caveolae and organizes macromolecular signaling complexes with
      effector proteins and membrane receptors. We report that long-term depression
      (LTD) elicited by a single application of the group I mGluR selective agonist
      (RS)-3,5-dihydroxyphenylglycine (DHPG) was markedly attenuated at Schaffer
      collateral-CA1 synapses of mice lacking caveolin-1 (Cav1(-/-)), as assessed by
      field recording. In contrast, multiple applications of DHPG produced LTD
      comparable to that in WT mice. Passive membrane properties, basal glutamatergic
      transmission and NMDA receptor (NMDAR)-dependent LTD were unaltered. The
      remaining LTD was reduced by anisomycin, an inhibitor of protein synthesis, by
      U0126, an inhibitor of MEK1/2 kinases, and by rapamycin, an inhibitor of
      mammalian target of rapamycin (mTOR), suggesting mediation by the same mechanisms
      as in WT. mGluR1/5-dependent activation (phosphorylation) of MEK and
      extracellular signal-regulated kinase (ERK1/2) was altered in Cav1(-/-) mice;
      basal phosphorylation was increased, but a single application of DHPG had no
      further effect, and after DHPG, phosphorylation was similar in WT and Cav1(-/-)
      mice. Taken together, our findings suggest that caveolin-1 is required for normal
      coupling of mGluR1/5 to downstream signaling cascades and induction of mGluR-LTD.

PMID- 21098663
TI  - Checkpoint genes and Exo1 regulate nearby inverted repeat fusions that form
      dicentric chromosomes in Saccharomyces cerevisiae.
AB  - Genomic rearrangements are common, occur by largely unknown mechanisms, and can
      lead to human diseases. We previously demonstrated that some genome
      rearrangements occur in budding yeast through the fusion of two DNA sequences
      that contain limited sequence homology, lie in inverted orientation, and are
      within 5 kb of one another. This inverted repeat fusion reaction forms dicentric
      chromosomes, which are well-known intermediates to additional rearrangements. We
      have previously provided evidence indicating that an error of stalled or
      disrupted DNA replication forks can cause inverted repeat fusion. Here we analyze
      how checkpoint protein regulatory pathways known to stabilize stalled forks
      affect this form of instability. We find that two checkpoint pathways suppress
      inverted repeat fusion, and that their activities are distinguishable by their
      interactions with exonuclease 1 (Exo1). The checkpoint kinase Rad53 (Chk2) and
      recombination protein complex MRX(MRN) inhibit Exo1 in one pathway, whereas in a
      second pathway the ATR-like kinases Mec1 and Tel1, adaptor protein Rad9, and
      effector kinases Chk1 and Dun1 act independently of Exo1 to prevent inverted
      repeat fusion. We provide a model that indicates how in Rad53 or MRX mutants, an
      inappropriately active Exo1 may facilitate faulty template switching between
      nearby inverted repeats to form dicentric chromosomes. We further investigate the
      role of Rad53, using hypomorphic alleles of Rad53 and null mutations in Rad9 and
      Mrc1, and provide evidence that only local, as opposed to global, activity of
      Rad53 is sufficient to prevent inverted repeat fusion.

PMID- 21098664
TI  - Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes.
AB  - Following its tyrosine phosphorylation, STAT3 is methylated on K140 by the
      histone methyl transferase SET9 and demethylated by LSD1 when it is bound to a
      subset of the promoters that it activates. Methylation of K140 is a negative
      regulatory event, because its blockade greatly increases the steady-state amount
      of activated STAT3 and the expression of many (i.e., SOCS3) but not all (i.e.,
      CD14) STAT3 target genes. Biological relevance is shown by the observation that
      overexpression of SOCS3 when K140 cannot be methylated blocks the ability of
      cells to activate STAT3 in response to IL-6. K140 methylation does not occur with
      mutants of STAT3 that do not enter nuclei or bind to DNA. Following treatment
      with IL-6, events at the SOCS3 promoter occur in an ordered sequence, as shown by
      chromatin immunoprecipitations. Y705-phosphoryl-STAT3 binds first and S727 is
      then phosphorylated, followed by the coincident binding of SET9 and dimethylation
      of K140, and lastly by the binding of LSD1. We conclude that the lysine
      methylation of promoter-bound STAT3 leads to biologically important down
      regulation of the dependent responses and that SET9, which is known to help
      provide an activating methylation mark to H3K4, is recruited to the newly
      activated SOCS3 promoter by STAT3.

PMID- 21098665
TI  - Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function
      to coordinate adaptation to synaptic inactivity.
AB  - Prolonged blockade of AMPA-type glutamate receptors in hippocampal neuron
      cultures leads to homeostatic enhancements of pre- and postsynaptic function that
      appear correlated at individual synapses, suggesting some form of transsynaptic
      coordination. The respective modifications are important for overall synaptic
      strength but their interrelationship, dynamics, and molecular underpinnings are
      unclear. Here we demonstrate that adaptation begins postsynaptically but is
      ultimately communicated to presynaptic terminals and expressed as an accelerated
      turnover of synaptic vesicles. Critical postsynaptic modifications occur over
      hours, but enable retrograde communication within minutes once AMPA receptor
      (AMPAR) blockade is removed, causing elevation of both spontaneous and evoked
      vesicle fusion. The retrograde signaling does not require spiking activity and
      can be interrupted by NBQX, philanthotoxin, postsynaptic BAPTA, or external
      sequestration of BDNF, consistent with the acute release of retrograde messenger,
      triggered by postsynaptic Ca(2+) elevation via Ca(2+)-permeable AMPARs.

PMID- 21098666
TI  - Large-scale identification and translocation of type IV secretion substrates by
      Coxiella burnetii.
AB  - Coxiella burnetii is an obligate intracellular bacterial pathogen responsible for
      acute and chronic Q fever. This bacterium harbors a type IV secretion system
      (T4SS) highly similar to the Dot/Icm of Legionella pneumophila that is believed
      to be essential for its infectivity. Protein substrates of the Coxiella T4SS are
      predicted to facilitate the biogenesis of a phagosome permissive for its
      intracellular growth. However, due to the lack of genetic systems, protein
      transfer by the C. burnetii Dot/Icm has not been demonstrated. In this study, we
      report the identification of 32 substrates of the C. burnetii Dot/Icm system
      using a fluorescence-based beta-lactamase (TEM1) translocation assay as well as
      the calmodulin-dependent adenylate cyclase (CyaA) assay in the surrogate host L.
      pneumophila. Notably, 26 identified T4SS substrates are hypothetical proteins
      without predicted function. Candidate secretion substrates were obtained by using
      (i) a genetic screen to identify C. burnetii proteins interacting with DotF, a
      component of the T4SS, and (ii) bioinformatic approaches to retrieve candidate
      genes that harbor characteristics associated with previously reported substrates
      of the Dot/Icm system from both C. burnetii and L. pneumophila. Moreover, we have
      developed a shuttle plasmid that allows the expression of recombinant proteins in
      C. burnetii as TEM fusion products. Using this system, we demonstrated that a
      Dot/Icm substrate identified with L. pneumophila was also translocated by C.
      burnetii in a process that requires its C terminus, providing direct genetic
      evidence of a functional T4SS in C. burnetii.

PMID- 21098667
TI  - Specific erythroid-lineage defect in mice conditionally deficient for Mediator
      subunit Med1.
AB  - The Mediator complex forms the bridge between transcriptional activators and the
      RNA polymerase II. Med1 (also known as PBP or TRAP220) is a key component of
      Mediator that interacts with nuclear hormone receptors and GATA transcription
      factors. Here, we show dynamic recruitment of GATA-1, TFIIB, Mediator, and RNA
      polymerase II to the beta-globin locus in induced mouse erythroid leukemia cells
      and in an erythropoietin-inducible hematopoietic progenitor cell line. Using Med1
      conditional knockout mice, we demonstrate a specific block in erythroid
      development but not in myeloid or lymphoid development, highlighted by the
      complete absence of beta-globin gene expression. Thus, Mediator subunit Med1
      plays a pivotal role in erythroid development and in beta-globin gene activation.

PMID- 21098668
TI  - A proton current drives action potentials in genetically identified sour taste
      cells.
AB  - Five tastes have been identified, each of which is transduced by a separate set
      of taste cells. Of these sour, which is associated with acid stimuli, is the
      least understood. Genetic ablation experiments have established that sour is
      detected by a subset of taste cells that express the TRP channel PKD2L1 and its
      partner PKD1L3, however the mechanisms by which this subset of cells detects
      acids remain unclear. Previous efforts to understand sour taste transduction have
      been hindered because sour responsive cells represent only a small fraction of
      cells in a taste bud, and numerous ion channels with no role in sour sensing are
      sensitive to acidic pH. To identify acid-sensitive conductances unique to sour
      cells, we created genetically modified mice in which sour cells were marked by
      expression of YFP under the control of the PKD2L1 promoter. To measure responses
      to sour stimuli we developed a method in which suction electrode recording is
      combined with UV photolysis of NPE-caged proton. Using these methods, we report
      that responses to sour stimuli are not mediated by Na(+) permeable channels as
      previously thought, but instead are mediated by a proton conductance specific to
      PKD2L1-expressing taste cells. This conductance is sufficient to drive action
      potential firing in response to acid stimuli, is enriched in the apical membrane
      of PKD2L1-expressing taste cells and is not affected by targeted deletion of the
      PKD1L3 gene. We conclude that, during sour transduction, protons enter through an
      apical proton conductance to directly depolarize the taste cell membrane.

PMID- 21098670
TI  - Mechanism of action and inhibition of dehydrosqualene synthase.
AB  - "Head-to-head" terpene synthases catalyze the first committed steps in sterol and
      carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form
      cyclopropylcarbinyl diphosphates, followed by ring opening. Here, we report the
      structures of Staphylococcus aureus dehydrosqualene synthase (CrtM) complexed
      with its reaction intermediate, presqualene diphosphate (PSPP), the
      dehydrosqualene (DHS) product, as well as a series of inhibitors. The results
      indicate that, on initial diphosphate loss, the primary carbocation so formed
      bends down into the interior of the protein to react with C2,3 double bond in the
      prenyl acceptor to form PSPP, with the lower two-thirds of both PSPP chains
      occupying essentially the same positions as found in the two farnesyl chains in
      the substrates. The second-half reaction is then initiated by the PSPP
      diphosphate returning back to the Mg(2+) cluster for ionization, with the
      resultant DHS so formed being trapped in a surface pocket. This mechanism is
      supported by the observation that cationic inhibitors (of interest as
      antiinfectives) bind with their positive charge located in the same region as the
      cyclopropyl carbinyl group; that S-thiolo-diphosphates only inhibit when in the
      allylic site; activity results on 11 mutants show that both DXXXD conserved
      domains are essential for PSPP ionization; and the observation that head-to-tail
      isoprenoid synthases as well as terpene cyclases have ionization and alkene-donor
      sites which spatially overlap those found in CrtM.

PMID- 21098669
TI  - Transspecies dimorphic allelic lineages of the proteasome subunit beta-type 8
      gene (PSMB8) in the teleost genus Oryzias.
AB  - The proteasome subunit beta-type 8 (PSMB8) gene in the jawed vertebrate MHC
      genomic region encodes a catalytic subunit of the immunoproteasome involved in
      the generation of peptides to be presented by the MHC class I molecules. A
      teleost, the medaka (Oryzias latipes), has highly diverged dimorphic allelic
      lineages of the PSMB8 gene with only about 80% amino acid identity, termed
      "PSMB8d" and "PSMB8N," which have been retained by most wild populations
      analyzed. To elucidate the evolutionary origin of these two allelic lineages,
      seven species of the genus Oryzias were analyzed for their PSMB8 allelic
      sequences using a large number of individuals from wild populations. All the
      PSMB8 alleles of these species were classified into one of these two allelic
      lineages based on their nucleotide sequences of exons and introns, indicating
      that the Oryzias PSMB8 gene has a truly dichotomous allelic lineage. Retention of
      both allelic lineages was confirmed except for one species. The PSMB8d lineage
      showed a higher frequency than the PSMB8N lineage in all seven species. The two
      allelic lineages showed curious substitutions at the 31st and 53rd residues of
      the mature peptide, probably involved in formation of the S1 pocket, suggesting
      that these allelic lineages show a functional difference in cleavage specificity.
      These results indicate that the PSMB8 dimorphism was established before
      speciation within the genus Oryzias and has been maintained for more than 30-60
      million years under a strict and asymmetric balancing selection through several
      speciation events.

PMID- 21098671
TI  - Relationship between Ca2+-affinity and shielding of bulk water in the Ca2+-pump
      from molecular dynamics simulations.
AB  - The sarcoplasmic reticulum Ca(2+)-ATPase transports two Ca(2+) per ATP hydrolyzed
      from the cytoplasm to the lumen against a large concentration gradient. During
      transport, the pump alters the affinity and accessibility for Ca(2+) by
      rearrangements of transmembrane helices. In this study, all-atom molecular
      dynamics simulations were performed for wild-type Ca(2+)-ATPase in the Ca(2+)
      bound form and the Gln mutants of Glu771 and Glu908. Both of them contribute only
      one carboxyl oxygen to site I Ca(2+), but only Glu771Gln completely looses the
      Ca(2+)-binding ability. The simulations show that: (i) For Glu771Gln, but not
      Glu908Gln, coordination of Ca(2+) was critically disrupted. (ii) Coordination
      broke at site II first, although Glu771 and Glu908 only contribute to site I.
      (iii) A water molecule bound to site I Ca(2+) and hydrogen bonded to Glu771 in
      wild-type, drastically changed the coordination of Ca(2+) in the mutant. (iv)
      Water molecules flooded the binding sites from the lumenal side. (v) The side
      chain conformation of Ile775, located at the head of a hydrophobic cluster near
      the lumenal surface, appears critical for keeping out bulk water. Thus the
      simulations highlight the importance of the water molecule bound to site I Ca(2+)
      and point to a strong relationship between Ca(2+)-coordination and shielding of
      bulk water, providing insights into the mechanism of gating of ion pathways in
      cation pumps.

PMID- 21098672
TI  - Lignin composition and structure in young versus adult Eucalyptus globulus
      plants.
AB  - Lignin changes during plant growth were investigated in a selected Eucalyptus
      globulus clone. The lignin composition and structure were studied in situ by a
      new procedure enabling the acquisition of two-dimensional nuclear magnetic
      resonance (2D-NMR) spectra on wood gels formed in the NMR tube as well as by
      analytical pyrolysis-gas chromatography-mass spectrometry. In addition, milled
      wood lignins were isolated and analyzed by 2D-NMR, pyrolysis-gas chromatography
      mass spectrometry, and thioacidolysis. The data indicated that p-hydroxyphenyl
      and guaiacyl units are deposited at the earlier stages, whereas the woods are
      enriched in syringyl (S) lignin during late lignification. Wood 2D-NMR showed
      that beta-O-4' and resinol linkages were predominant in the eucalypt lignin,
      whereas other substructures were present in much lower amounts. Interestingly,
      open beta-1' structures could be detected in the isolated lignins.
      Phenylcoumarans and cinnamyl end groups were depleted with age, spirodienone
      abundance increased, and the main substructures (beta-O-4' and resinols) were
      scarcely modified. Thioacidolysis revealed a higher predominance of S units in
      the ether-linked lignin than in the total lignin and, in agreement with NMR, also
      indicated that resinols are the most important nonether linkages. Dimer analysis
      showed that most of the resinol-type structures comprised two S units
      (syringaresinol), the crossed guaiacyl-S resinol appearing as a minor
      substructure and pinoresinol being totally absent. Changes in hemicelluloses were
      also shown by the 2D-NMR spectra of the wood gels without polysaccharide
      isolation. These include decreases of methyl galacturonosyl, arabinosyl, and
      galactosyl (anomeric) signals, assigned to pectin and related neutral
      polysaccharides, and increases of xylosyl (which are approximately 50%
      acetylated) and 4-O-methylglucuronosyl signals.

PMID- 21098673
TI  - The role of alpha-glucosidase in germinating barley grains.
AB  - The importance of alpha-glucosidase in the endosperm starch metabolism of barley
      (Hordeum vulgare) seedlings is poorly understood. The enzyme converts maltose to
      glucose (Glc), but in vitro studies indicate that it can also attack starch
      granules. To discover its role in vivo, we took complementary chemical-genetic
      and reverse-genetic approaches. We identified iminosugar inhibitors of a
      recombinant form of an alpha-glucosidase previously discovered in barley
      endosperm (ALPHA-GLUCOSIDASE97 [HvAGL97]), and applied four of them to
      germinating grains. All four decreased the Glc-to-maltose ratio in the endosperm
      10 d after imbibition, implying inhibition of maltase activity. Three of the four
      inhibitors also reduced starch degradation and seedling growth, but the fourth
      did not affect these parameters. Inhibition of starch degradation was apparently
      not due to inhibition of amylases. Inhibition of seedling growth was primarily a
      direct effect of the inhibitors on roots and coleoptiles rather than an indirect
      effect of the inhibition of endosperm metabolism. It may reflect inhibition of
      glycoprotein-processing glucosidases in these organs. In transgenic seedlings
      carrying an RNA interference silencing cassette for HvAgl97, alpha-glucosidase
      activity was reduced by up to 50%. There was a large decrease in the Glc-to
      maltose ratio in these lines but no effect on starch degradation or seedling
      growth. Our results suggest that the alpha-glucosidase HvAGL97 is the major
      endosperm enzyme catalyzing the conversion of maltose to Glc but is not required
      for starch degradation. However, the effects of three glucosidase inhibitors on
      starch degradation in the endosperm indicate the existence of unidentified
      glucosidase(s) required for this process.

PMID- 21098674
TI  - Genome-wide computational function prediction of Arabidopsis proteins by
      integration of multiple data sources.
AB  - Although Arabidopsis (Arabidopsis thaliana) is the best studied plant species,
      the biological role of one-third of its proteins is still unknown. We developed a
      probabilistic protein function prediction method that integrates information from
      sequences, protein-protein interactions, and gene expression. The method was
      applied to proteins from Arabidopsis. Evaluation of prediction performance showed
      that our method has improved performance compared with single source-based
      prediction approaches and two existing integration approaches. An innovative
      feature of our method is that it enables transfer of functional information
      between proteins that are not directly associated with each other. We provide
      novel function predictions for 5,807 proteins. Recent experimental studies
      confirmed several of the predictions. We highlight these in detail for proteins
      predicted to be involved in flowering and floral organ development.

PMID- 21098675
TI  - Callose synthase GSL7 is necessary for normal phloem transport and inflorescence
      growth in Arabidopsis.
AB  - One isoform of callose synthase, Glucan Synthase-Like7 (GSL7), is tightly
      coexpressed with two isoforms of sucrose synthase (SUS5 and SUS6) known to be
      confined to phloem sieve elements in Arabidopsis (Arabidopsis thaliana).
      Investigation of the phenotype of gsl7 mutants of Arabidopsis revealed that the
      sieve plate pores of stems and roots lack the callose lining seen in wild-type
      plants. Callose synthesis in other tissues of the plant appears to be unaffected.
      Although gsl7 plants show only minor phenotypic alterations during vegetative
      growth, flowering stems are reduced in height and all floral parts are smaller
      than those of wild-type plants. Several lines of evidence suggest that the
      reduced growth of the inflorescence is a result of carbohydrate starvation.
      Levels of sucrose, hexoses, and starch are lower in the terminal bud clusters of
      gsl7 than in those of wild-type plants. Transcript levels of "starvation" genes
      expressed in response to low sugars are elevated in the terminal bud clusters of
      gsl7 plants, at the end of the night, and during an extended night. Pulse-chase
      experiments with (14)CO(2) show that transport of assimilate in the flowering
      stem is much slower in gsl7 mutants than in wild-type plants. We suggest that the
      callose lining of sieve plate pores is essential for normal phloem transport
      because it confers favorable flow characteristics on the pores.

PMID- 21098676
TI  - Induction of BAP1 by a moderate decrease in temperature is mediated by ICE1 in
      Arabidopsis.
AB  - Temperature variations at the nonextreme range modulate various processes of
      plant growth, development, and physiology, but how plants perceive and transduce
      these temperature signals is not well understood. Moderate cooling from 28 
      degrees C to 22  degrees C induces transcription of a number of genes in
      salicylic acid-dependent and -independent manners. Here, we report the study of
      the transcriptional control of the BON1-associated protein1 (BAP1) gene that is
      responsive to a moderate decrease of temperature as well as to many environmental
      stimuli. Using reporter genes under the control of series of regions of the BAP1
      promoter, we identified a 35-bp fragment that is necessary and sufficient for the
      BAP1 transcript induction by a moderate cooling. This fragment also confers an
      induction of BAP1 by cold and reactive oxygen species-generating paraquat.
      Furthermore, the inducer of CBF expression1 (ICE1) protein that is involved in
      transcriptional control of cold responses is found to bind to a MYC element in
      this promoter and is required for the cooling induction of BAP1. The ice1 mutant
      has a low induction of BAP1 and enhanced resistance to a bacterial pathogen.
      Thus, responses to a moderate decrease in temperature may utilize components in
      the cold response as well as a potentiating signaling involving salicylic acid.

PMID- 21098677
TI  - The GDC1 gene encodes a novel ankyrin domain-containing protein that is essential
      for grana formation in Arabidopsis.
AB  - In land-plant chloroplasts, the grana play multiple roles in photosynthesis,
      including the potential increase of photosynthetic capacity in light and
      enhancement of photochemical efficiency in shade. However, the molecular
      mechanisms of grana formation remain elusive. Here, we report a novel gene, Grana
      Deficient Chloroplast1 (GDC1), required for chloroplast grana formation in
      Arabidopsis (Arabidopsis thaliana). In the chloroplast of knockout mutant gdc1-3,
      only stromal thylakoids were observed, and they could not stack together to form
      appressed grana. The mutant exhibited seedling lethality with pale green
      cotyledons and true leaves. Further blue native-polyacrylamide gel
      electrophoresis analysis indicated that the trimeric forms of Light-Harvesting
      Complex II (LHCII) were scarcely detected in gdc1-3, confirming previous reports
      that the LHCII trimer is essential for grana formation. The Lhcb1 protein, the
      major component of the LHCIIb trimer, was substantially reduced, and another
      LHCIIb trimer component, Lhcb2, was slightly reduced in the gdc1-3 mutant,
      although their transcription levels were not altered in the mutant. This suggests
      that defective LHCII trimer formation in gdc1-3 is due to low amounts of Lhcb1
      and Lhcb2. GDC1 encodes a chloroplast protein with an ankyrin domain within the
      carboxyl terminus. It was highly expressed in Arabidopsis green tissues, and its
      expression was induced by photosignaling pathways. Immunoblot analysis of the
      GDC1-green fluorescent protein (GFP) fusion protein in 35S::GDC1-GFP transgenic
      plants with GFP antibody indicates that GDC1 is associated with an approximately
      440-kD thylakoid protein complex instead of the LHCII trimer. This shows that
      GDC1 may play an indirect role in LHCII trimerization during grana formation.

PMID- 21098678
TI  - Involvement of Arabidopsis RACK1 in protein translation and its regulation by
      abscisic acid.
AB  - Earlier studies have shown that RACK1 functions as a negative regulator of
      abscisic acid (ABA) responses in Arabidopsis (Arabidopsis thaliana), but the
      molecular mechanism of the action of RACK1 in these processes remains elusive.
      Global gene expression profiling revealed that approximately 40% of the genes
      affected by ABA treatment were affected in a similar manner by the rack1
      mutation, supporting the view that RACK1 is an important regulator of ABA
      responses. On the other hand, coexpression analysis revealed that more than 80%
      of the genes coexpressed with RACK1 encode ribosome proteins, implying a close
      relationship between RACK1's function and the ribosome complex. These results
      implied that the regulatory role for RACK1 in ABA responses may be partially due
      to its putative function in protein translation, which is one of the major
      cellular processes that mammalian and Saccharomyces cerevisiae RACK1 is involved
      in. Consistently, all three Arabidopsis RACK1 homologous genes, namely RACK1A,
      RACK1B, and RACK1C, complemented the growth defects of the S. cerevisiae cross
      pathway control2/rack1 mutant. In addition, RACK1 physically interacts with
      Arabidopsis Eukaryotic Initiation Factor6 (eIF6), whose mammalian homolog is a
      key regulator of 80S ribosome assembly. Moreover, rack1 mutants displayed
      hypersensitivity to anisomycin, an inhibitor of protein translation, and
      displayed characteristics of impaired 80S functional ribosome assembly and 60S
      ribosomal subunit biogenesis in a ribosome profiling assay. Gene expression
      analysis revealed that ABA inhibits the expression of both RACK1 and eIF6. Taken
      together, these results suggest that RACK1 may be required for normal production
      of 60S and 80S ribosomes and that its action in these processes may be regulated
      by ABA.

PMID- 21098682
TI  - Defining a relationship between dietary fatty acids and the cytochrome P450
      system in a mouse model of fatty liver disease.
AB  - Liver-specific ablation of cytochrome P450 reductase in mice (LCN) results in
      hepatic steatosis that can progress to steatohepatitis characterized by
      inflammation and fibrosis. The specific cause of the fatty liver phenotype is
      poorly understood but is hypothesized to result from elevated expression of genes
      encoding fatty acid synthetic genes. Since expression of these genes is known to
      be suppressed by polyunsaturated fatty acids, we performed physiological and
      genomics studies to evaluate the effects of dietary linoleic and linolenic fatty
      acids (PUFA) or arachidonic and decosahexaenoic acids (HUFA) on the hepatic
      phenotypes of control and LCN mice by comparison with a diet enriched in
      saturated fatty acids. The dietary interventions with HUFA reduced the fatty
      liver phenotype in livers of LCN mice and altered the gene expression patterns in
      these livers to more closely resemble those of control mice. Importantly, the
      expression of genes encoding lipid pathway enzymes were not different between
      controls and LCN livers, indicating a strong influence of diet over POR genotype.
      These analyses highlighted the impact of POR ablation on expression of genes
      encoding P450 enzymes and proteins involved in stress and inflammation. We also
      found that livers from animals of both genotypes fed diets enriched in PUFA had
      gene expression patterns more closely resembling those fed diets enriched in
      saturated fatty acids. These results strongly suggest only HUFA supplied from an
      exogenous source can suppress hepatic lipogenesis.

PMID- 21098683
TI  - Transcription factor MIST1 in terminal differentiation of mouse and human plasma
      cells.
AB  - Despite their divergent developmental ancestry, plasma cells and gastric
      zymogenic (chief) cells share a common function: high-capacity secretion of
      protein. Here we show that both cell lineages share increased expression of a
      cassette of 269 genes, most of which regulate endoplasmic reticulum (ER) and
      Golgi function, and they both induce expression of the transcription factors X
      box binding protein 1 (Xbp1) and Mist1 during terminal differentiation. XBP1 is
      known to augment plasma cell function by establishing rough ER, and MIST1
      regulates secretory vesicle trafficking in zymogenic cells. We examined
      morphology and function of plasma cells in wild-type and Mist1(-/-) mice and
      found subtle differences in ER structure but no overall defect in plasma cell
      function, suggesting that Mist1 may function redundantly in plasma cells. We next
      reasoned that MIST1 might be useful as a novel and reliable marker of plasma
      cells. We found that MIST1 specifically labeled normal plasma cells in mouse and
      human tissues, and, moreover, its expression was also characteristic of plasma
      cell differentiation in a cohort of 12 human plasma cell neoplasms. Overall, our
      results show that MIST1 is enriched upon plasma cell differentiation as a part of
      a genetic program facilitating secretory cell function and also that MIST1 is a
      novel marker of normal and neoplastic plasma cells in mouse and human tissues.

PMID- 21098684
TI  - Appetite-regulating hormones cortisol and peptide YY are associated with
      disordered eating psychopathology, independent of body mass index.
AB  - OBJECTIVE: Disordered eating occurs in women at both weight extremes of anorexia
      nervosa (AN) and obesity. Cortisol, peptide YY (PYY), leptin, and ghrelin are
      hormones involved in appetite and feeding behavior that vary with weight and body
      fat. Abnormal levels of these hormones have been reported in women with AN,
      functional hypothalamic amenorrhea (HA), and obesity. The relationship between
      appetite-regulating hormones and disordered eating psychopathology is unknown. We
      therefore studied the relationship between orexigenic and anorexigenic hormones
      and disordered eating psychopathology in women across a range of weights. DESIGN:
      A cross-sectional study of 65 women, 18-45 years: 16 with AN, 12 normal-weight
      with HA, 17 overweight or obese, and 20 normal-weight in good health. METHODS:
      Two validated measures of disordered eating psychopathology, the Eating Disorders
      Examination-Questionnaire (EDE-Q) and Eating Disorders Inventory-2 (EDI-2), were
      administered. Fasting PYY, leptin, and ghrelin levels were measured; cortisol
      levels were pooled from serum samples obtained every 20 min from 2000 to 0800 h.
      RESULTS: Cortisol and PYY levels were positively associated with disordered
      eating psychopathology including restraint, eating concerns, and body image
      disturbance, independent of body mass index (BMI). Although leptin levels were
      negatively associated with disordered eating psychopathology, these relationships
      were not significant after controlling for BMI. Ghrelin levels were generally not
      associated with EDE-Q or EDI-2 scores. CONCLUSIONS: Higher levels of cortisol and
      PYY are associated with disordered eating psychopathology independent of BMI in
      women across the weight spectrum, suggesting that abnormalities in appetite
      regulation may be associated with specific eating disorder pathologies.

PMID- 21098685
TI  - Pregnancy in women heterozygous for MCT8 mutations: risk of maternal
      hypothyroxinemia and fetal care.
AB  - CONTEXT: Monocarboxylate transporter 8 (MCT8 or SLC16A2) mutations cause X-linked
      Allan-Herndon-Dudley syndrome. Heterozygous females are usually asymptomatic, but
      pregnancy may modify thyroid function and MCT8 is expressed in the placenta,
      suggesting that maternal and fetal abnormalities might develop even in the
      absence of MCT8 fetal mutation. Genetic counseling is so far based on X-linked
      transmission, and prenatal diagnosis is rarely performed. OBJECTIVE: To describe
      thyroid function and the prenatal diagnosis in pregnant mothers harboring
      heterozygous MCT8 mutations and management of the persistent maternal
      hypothyroxinemia. Patients Two women heterozygous for MCT8 mutations (c.1690G>A
      and c.1393-1G>C) were monitored throughout pregnancy. METHODS: Prenatal diagnosis
      included sex determination, direct MCT8 sequencing, and familial linkage
      analysis. Ultrasonography and hormonal assays for maternal thyroid function
      evaluation were performed serially during pregnancy. Neonatal thyroid hormonal
      status was assessed. RESULTS: None of the three fetuses (two males and one
      female) carried MCT8 mutations. One of the two heterozygous mothers revealed
      gestational hypothyroxinemia, prompting early levothyroxine (l-T4) therapy until
      delivery. The second heterozygous mother showed normal thyroid function but was
      preventively traited by l-T4 and all of the three neonates had normal thyroid
      hormone levels and thyroid gland at birth, suggesting advantages of prenatal care
      and/or compensatory mechanisms. CONCLUSION: Heterozygous MCT8 women should be
      monitored for requirement of l-T4 therapy to prevent fetal and neonatal
      hypothyroidism and to avoid risk of potential cognitive delay due to gestational
      hypothyroxinemia. Moreover, when the disease-causing mutation is known and/or the
      first child is affected, prenatal diagnosis for male fetuses should be assessed
      early for MCT8 mutations by direct sequencing.

PMID- 21098686
TI  - Cardiovascular risk, metabolic profile, and body composition in adult males with
      congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - OBJECTIVE: Lifelong glucocorticoid therapy in patients with congenital adrenal
      hyperplasia (CAH) or the disease per se may result in increased cardiovascular
      risk. We therefore investigated cardiovascular and metabolic risk profiles in
      adult CAH males. SUBJECTS AND METHODS: We compared CAH males (n = 30), 19-67
      years old, with age- and sex-matched controls (n = 32). Subgroups of different
      ages (< 30 years or older) and CYP21A2 genotypes (null, I2splice, and I172N as
      the mildest mutation) were studied. Anthropometry, fat and lean mass measured by
      dual-energy X-ray absorptiometry, lipids, liver function tests, homocysteine,
      lipoprotein-(a), glucose and insulin during an oral glucose tolerance test
      (OGTT), urine albumin, adrenal hormones, and 24 h ambulatory blood pressure
      measurements were studied. RESULTS: CAH males were shorter. Waist/hip ratio and
      fat mass were higher in older patients and the I172N group. Heart rate was faster
      in older patients, the I2splice, and I172N groups. Insulin levels were increased
      during OGTT in all patients and in the I172N group. gamma-glutamyl transpeptidase
      was increased in older patients and in the I172N group. Testosterone was lower in
      older patients. Homocysteine was lower in younger patients, which may be
      cardioprotective. The cardiovascular risk seemed higher with
      hydrocortisone/cortisone acetate than prednisolone. Urinary epinephrine was lower
      in all groups of patients except in I172N. CONCLUSIONS: Indications of increased
      risk were found in CAH males >= 30 years old and in the I172N group. In contrast,
      younger CAH males did not differ from age-matched controls. This is likely to
      reflect a better management in recent years.

PMID- 21098687
TI  - Psychological and behavioural aspects in children and adolescents with congenital
      hypothyroidism diagnosed by neonatal screening: comparison between parents' and
      children's perceptions.
AB  - OBJECTIVE: To compare the psychological adjustment and behaviour of congenital
      hypothyroidism (CH) children and their parents with a control group. STUDY
      DESIGN: A cross-sectional study was carried out with 84 CH subjects diagnosed by
      neonatal screening (range 2.7-18.6 years), subdivided into four age groups: group
      1 (2-5 years); group 2 (6-10 years); group 3 (11-13 years); and group 4 (14-18
      years) and was compared with an age-matched control group. Patients were assessed
      using two questionnaires: Child Behaviour Checklist for parents and Youth Self
      Report for children over 11 years of age. RESULTS: In groups 1, 3 and 4, total
      score (TS), internalising score (IS=problems within the self) and externalising
      score (ES=conflicts with other people) as reported by parents were not
      significantly different in CH patients and in controls. In group 2, parents of CH
      children showed values of TS (P<0.05), IS (P<0.05), ES (P<0.05) and scores on
      other scales significantly higher than controls. In self-reports of groups 3 and
      4, the behavioural scales were not significantly different in CH patients and in
      controls. CONCLUSIONS: Paediatricians should be informed about the increased risk
      of the development of behavioural problems at primary school age in CH patients.
      At this age special attention should be paid to parental worries and anxiety.
      However, it can be reassuring for the patients and parents to know that the
      problems may be related to CH, and that they may spontaneously disappear.

PMID- 21098688
TI  - Fatal dysrhythmia following initiation of lansoprazole during a long-term course
      of voriconazole.

PMID- 21098689
TI  - D-penicillamine interferes with S-homocysteinylation and S-cysteinylation of LDL
      apolipoprotein B.

PMID- 21098679
TI  - Comparative functional genomic analysis of Solanum glandular trichome types.
AB  - Glandular trichomes play important roles in protecting plants from biotic attack
      by producing defensive compounds. We investigated the metabolic profiles and
      transcriptomes to characterize the differences between different glandular
      trichome types in several domesticated and wild Solanum species: Solanum
      lycopersicum (glandular trichome types 1, 6, and 7), Solanum habrochaites (types
      1, 4, and 6), Solanum pennellii (types 4 and 6), Solanum arcanum (type 6), and
      Solanum pimpinellifolium (type 6). Substantial chemical differences in and
      between Solanum species and glandular trichome types are likely determined by the
      regulation of metabolism at several levels. Comparison of S. habrochaites type 1
      and 4 glandular trichomes revealed few differences in chemical content or
      transcript abundance, leading to the conclusion that these two glandular trichome
      types are the same and differ perhaps only in stalk length. The observation that
      all of the other species examined here contain either type 1 or 4 trichomes (not
      both) supports the conclusion that these two trichome types are the same. Most
      differences in metabolites between type 1 and 4 glands on the one hand and type 6
      glands on the other hand are quantitative but not qualitative. Several glandular
      trichome types express genes associated with photosynthesis and carbon fixation,
      indicating that some carbon destined for specialized metabolism is likely fixed
      within the trichome secretory cells. Finally, Solanum type 7 glandular trichomes
      do not appear to be involved in the biosynthesis and storage of specialized
      metabolites and thus likely serve another unknown function, perhaps as the site
      of the synthesis of protease inhibitors.

PMID- 21098690
TI  - Model-based analysis of covariate effects on population pharmacokinetics of
      thrombomodulin alfa in patients with disseminated intravascular coagulation and
      normal subjects.
AB  - Thrombomodulin alfa is the recombinant extracellular domain of human
      thrombomodulin, which shows anticoagulation activity. To elucidate the
      pharmacokinetics of thrombomodulin alfa in patients with disseminated
      intravascular coagulation (DIC), population pharmacokinetic (PPK) analysis was
      performed using plasma concentration data obtained in phase 1 (20 patients, 348
      time points) and phase 2 (116 patients, 305 time points) clinical trials. The
      actual and predicted plasma concentrations of thrombomodulin alfa based on the
      final PPK model showed a good linear correlation (R = 0.9504), and the
      pharmacokinetics of thrombomodulin alfa in DIC patients were affected by body
      weight, age, renal dysfunction, and hematocrit value. The distribution volume and
      clearance (CL) were proportional to body weight and were significantly increased
      in patients with lower hematocrit value (male <40%, female <35%). Furthermore, CL
      was decreased in patients with renal dysfunction and in elderly patients. Based
      on these results, the standard dose of thrombomodulin alfa is adjusted according
      to body weight. However, further dose adjustment is not needed based on age and
      hematocrit value, since these factors did not cause the large changes in plasma
      concentration that can affect the efficacy or safety.

PMID- 21098691
TI  - Adherence to oral hypoglycemic agents in 26,782 Chinese patients: a cohort study.
AB  - This study evaluated the factors associated with adherence to oral hypoglycemic
      agents (OHAs) among Chinese patients. A validated clinical database was used to
      include all adult patients who were prescribed an OHA in any of the government
      clinics in a large territory of Hong Kong from January 1, 2004, to June 30, 2007
      and made 1 or more subsequent visits for OHA refill. Patients with medication
      possession ratio (MPR) 0.8 or greater were regarded as medication adherent. One
      binary logistic regression analysis was performed to test the association between
      age, gender, visit types (new vs follow-up visits), and MPR while controlling for
      socioeconomic status, service settings, number of comorbidities, and the
      medication class prescribed (sulphonylurea vs biguanide vs combination of both).
      Among 26,782 patients, 89.6% were adherent. Older patients (aged 50-59 years;
      adjusted odds ratio [AOR] 1.19; 95% confidence interval [CI], 1.06-1.34, P =
      .004; 60-69 years; AOR 1.37; 95% CI, 1.21-1.55, P < .001; >=70 years; AOR 1.52;
      95% CI, 1.34-1.72, P < .001) and follow-up visitors (AOR 3.89; 95% CI, 3.55-4.27,
      P < .001) were more likely to be medication adherent. Male subjects were less
      likely to adhere (AOR 0.84; 95% CI, 0.77-0.91, P < .001). Newer medication
      adherence-enhancing strategies should be implemented, especially among younger
      patients, male subjects, and new clinic attendees to secure optimal adherence.

PMID- 21098692
TI  - A randomized study of the effects of food on the pharmacokinetics of once-daily
      extended-release hydromorphone in healthy volunteers.
AB  - This randomized, open-label, crossover study investigated the influence of food
      on the pharmacokinetics of extended-release hydromorphone in 30 healthy
      volunteers. Participants received extended-release hydromorphone 16 mg in the
      fasted state and immediately after a high-fat breakfast. In addition, the
      pharmacokinetics of a 16-mg dose of extended-release hydromorphone and a 16-mg
      daily dose (4 mg qid) of immediate-release hydromorphone in the fasted state were
      compared. Treatments were separated by washout periods of 7 to 14 days.
      Naltrexone was given throughout each treatment period to block the opioid effects
      of hydromorphone. The 90% confidence intervals (CIs) of the ratios of geometric
      means for maximum plasma concentrations (C(max)) and area under the plasma
      concentration-time curve (AUC) for extended-release hydromorphone in the fed and
      fasted states were within the bioequivalence criteria range of 80% to 125%. In
      the fasted state, the 90% CIs of the ratios of AUC geometric means for extended
      release hydromorphone and immediate-release hydromorphone were also within the
      bioequivalence range. Both hydromorphone treatments were well tolerated. This
      study shows that the bioavailability of extended-release hydromorphone is not
      affected by food and that the bioavailability of extended-release hydromorphone
      under fasting conditions is comparable with that of the immediate-release
      formulation when administered at the same total daily dose.

PMID- 21098693
TI  - Teaching from catastrophe: using therapeutic misadventures from hydromorphone to
      teach key principles in clinical pharmacology.

PMID- 21098694
TI  - Pharmacokinetics, safety, and biologic effects of azithromycin in extremely
      preterm infants at risk for ureaplasma colonization and bronchopulmonary
      dysplasia.
AB  - Ureaplasma spp. respiratory tract colonization is a significant risk factor for
      bronchopulmonary dysplasia (BPD), a chronic lung disorder in preterm infants. As
      an initial step preparatory to future clinical trials to evaluate the clinical
      efficacy of azithromycin to prevent BPD, the authors characterized the
      pharmacokinetics, safety, and biological effects of a single intravenous dose of
      azithromycin (10 mg/kg) in preterm neonates (n = 12) 24 to 28 weeks gestation at
      risk for Ureaplasma infection and BPD. A 2-compartment structural model with the
      clearance and volume of peripheral compartment (V2) allometrically scaled on body
      weight (WT) best described the pharmacokinetics of azithromycin in preterm
      neonates. The estimated parameters were clearance [0.18 L/h * WT(kg)(0.75)],
      intercompartmental clearance [1.0 L/h], volume of distribution of central
      compartment [0.93 L], and V2 [14.2 L * WT(kg)]. There were no serious adverse
      events attributed to azithromycin. A single dose of azithromycin did not suppress
      inflammatory cytokines or myeloperoxidase activity in tracheal aspirates. These
      results demonstrated the safety of azithromycin and developed a pharmacokinetic
      model that is useful for future simulation-based clinical trials for eradicating
      Ureaplasma and preventing BPD in preterm neonates.

PMID- 21098695
TI  - Preoperative circulating tumor cell detection using the isolation by size of
      epithelial tumor cell method for patients with lung cancer is a new prognostic
      biomarker.
AB  - PURPOSE: Pathologic TNM staging is currently the best prognostic factor for non
      small cell lung carcinoma (NSCLC). However, even in early-stage NSCLC, the
      recurrence rates after surgery range from 25% to 50%. The preoperative detection
      of circulating tumor cells (CTC) could be useful to tailor new therapeutic
      strategies in NSCLC. We assessed the presence of CTC in NSCLC patients undergoing
      surgery, using cytologic analyses, after their isolation by size of epithelial
      tumor cells (ISET method). The presence and the number of CTCs were considered
      and correlated with clinicopathologic parameters including patient follow-up.
      EXPERIMENTAL DESIGN: Of the 247 blood samples tested, 208 samples were from
      patients with resectable NSCLC and 39 from healthy subjects. The mean follow-up
      was 24 months. An image of detected cells with presumably nonhematologic features
      [initially defined as "circulating nonhematologic cells" (CNHC)] was recorded.
      The presence of CNHC was assessed blindly and independently by 10
      cytopathologists, using cytologic criteria of malignancy on stained filters. The
      count of detected CNHCs was made for each filter. RESULTS: One hundred two of 208
      (49%) patients showed CNHCs corresponding to CNHC with malignant cytopathologic
      features in 76 of 208 (36%) cases. CNHCs were not detected in the control group.
      A level of 50 or more CNHCs corresponding to the third quartile was associated
      with shorter overall and disease-free-survival, independently of disease staging,
      and with a high risk of recurrence and death in early-stage I + II-resectable
      NSCLC. CONCLUSION: A high percentage of NSCLC patients show preoperative
      detection of CNHC by the ISET method. The presence and level of 50 or more CNHCs
      are associated with worse survival of patients with resectable NSCLC.

PMID- 21098696
TI  - Nutlin-3a is a potential therapeutic for ewing sarcoma.
AB  - PURPOSE: Although mutations in the TP53 gene occur in half of all cancers,
      approximately 90% of Ewing sarcomas retain a functional wild-type p53. The low
      frequency of TP53 alterations in Ewing sarcoma makes this tumor type an ideal
      candidate for p53-targeted therapies. In this study, we have examined the
      molecular and cellular responses of cultured Ewing sarcoma cell lines following
      exposure to Nutlin-3a, a recently developed MDM2 antagonist. EXPERIMENTAL DESIGN:
      The ability of Nutlin-3a to impart apoptosis or cell cycle arrest in a p53
      dependent manner was determined in a comprehensive panel of Ewing sarcoma cell
      lines. The capacity of Nutlin-3a to augment the antitumor activity of MDM4
      antagonists and cytotoxic agents currently used in the clinical treatment of
      Ewing sarcoma was also investigated. RESULTS: Apoptosis was the primary response
      of wild-type p53 expressing Ewing sarcoma cell lines. The cytotoxicity of Nultin
      3a was also synergistic with the chemotherapeutic agents, vincristine,
      actinomycin D, doxorubicin, and etoposide in a concentration-dependent manner.
      Significant MDM4 protein overexpression was observed in Ewing sarcoma cell lines
      of wild-type p53 status, providing a mechanism through which Ewing sarcomas can
      develop in the absence of TP53 alterations. This study provides the first
      evidence of synergism between targeted inhibition of MDM2 and MDM4. CONCLUSION:
      Our findings suggest that p53-dependent apoptosis is the primary cellular
      response of Ewing sarcoma cell lines following exposure to Nutlin-3a.
      Furthermore, Nutlin-3a can synergize with the current Ewing sarcoma chemotherapy
      protocols, suggesting p53 activation as a novel systemic therapeutic approach for
      this disease.

PMID- 21098697
TI  - Expression and functional significance of HtrA1 loss in endometrial cancer.
AB  - PURPOSE: The purpose of this study was to determine if loss of serine protease
      HtrA1 in endometrial cancer will promote the invasive potential of EC cell lines.
      EXPERIMENTAL DESIGN: Western blot analysis and immunohistochemistry methods were
      used to determine HtrA1 expression in EC cell lines and primary tumors,
      respectively. Migration, invasion assays and in vivo xenograft experiment were
      performed to compare the extent of metastasis between HtrA1 expressing and HtrA1
      knocked down clones. RESULTS: Western blot analysis of HtrA1 in 13 EC cell lines
      revealed complete loss of HtrA1 expression in all seven papillary serous EC cell
      lines. Downregulation of HtrA1 in Hec1A and Hec1B cell lines resulted in a three-
      to fourfold increase in the invasive potential. Exogenous expression of HtrA1 in
      Ark1 and Ark2 cells resulted in three- to fourfold decrease in both invasive and
      migration potential of these cells. There was an increased rate of metastasis to
      the lungs associated with HtrA1 downregulation in Hec1B cells compared to control
      cells with endogenous HtrA1 expression. Enhanced expression of HtrA1 in Ark2
      cells resulted in significantly less tumor nodules metastasizing to the lungs
      compared to parental or protease deficient (SA mutant) Ark2 cells.
      Immunohistochemical analysis showed 57% (105/184) of primary EC tumors had low
      HtrA1 expression. The association of low HtrA1 expression with high-grade
      endometrioid tumors was statistically significant (P = 0.016). CONCLUSIONS:
      Collectively, these data indicate loss of HtrA1 may contribute to the
      aggressiveness and metastatic ability of endometrial tumors.

PMID- 21098698
TI  - Plectin-1 as a novel biomarker for pancreatic cancer.
AB  - PURPOSE: We are in great need of specific biomarkers to detect pancreatic ductal
      adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1
      (Plec1) was recently identified as one such biomarker. However, its suitability
      as a specific biomarker for human pancreatic cancer, and its usability as an
      imaging target, remain to be assessed. EXPERIMENTAL DESIGN: Specimens of human
      PDAC, chronic pancreatitis, and normal pancreata were evaluated by
      immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging
      target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single
      photon emission computed tomography in an orthotopic and liver metastasis murine
      model of PDAC. RESULTS: Plec1 expression was noted to be positive in all PDACs
      but negative in benign tissues. Plec1 expression increases during pancreatic
      carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC
      precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression
      was further noted to be retained in all metastatic foci assayed and clearly
      highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In
      vivo imaging using tPTP specifically highlighted the primary and metastatic
      tumors. Biodistribution studies performed after imaging show that the primary
      pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over
      normal pancreas and 1.7-fold over normal liver. CONCLUSIONS: Plec1 is the first
      biomarker to identify primary and metastatic PDAC by imaging and may also detect
      preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore
      improve detection and staging.

PMID- 21098699
TI  - Molecular histopathology by spectrally reconstructed nonlinear interferometric
      vibrational imaging.
AB  - Sensitive assays for rapid quantitative analysis of histologic sections, resected
      tissue specimens, or in situ tissue are highly desired for early disease
      diagnosis. Stained histopathology is the gold standard but remains a subjective
      practice on processed tissue taking from hours to days. We describe a microscopy
      technique that obtains a sensitive and accurate color-coded image from intrinsic
      molecular markers. Spectrally reconstructed nonlinear interferometric vibrational
      imaging can differentiate cancer versus normal tissue sections with greater than
      99% confidence interval in a preclinical rat breast cancer model and define
      cancer boundaries to +/- 100 MUm with greater than 99% confidence interval, using
      fresh unstained tissue sections imaged in less than 5 minutes. By optimizing
      optical sources and beam delivery, this technique can potentially enable real
      time point-of-care optical molecular imaging and diagnosis.

PMID- 21098700
TI  - Persistent activation of the Fyn/ERK kinase signaling axis mediates imatinib
      resistance in chronic myelogenous leukemia cells through upregulation of
      intracellular SPARC.
AB  - SPARC is an extracellular matrix protein that exerts pleiotropic effects on
      extracellular matrix organization, growth factor availability, cell adhesion,
      differentiation, and immunity in cancer. Chronic myelogenous leukemia (CML) cells
      resistant to the BCR-ABL inhibitor imatinib (IM-R cells) were found to
      overexpress SPARC mRNA. In this study, we show that imatinib triggers SPARC
      accumulation in a variety of tyrosine kinase inhibitor (TKI)-resistant CML cell
      lines. SPARC silencing in IM-R cells restored imatinib sensitivity, whereas
      enforced SPARC expression in imatinib-sensitive cells promoted viability as well
      as protection against imatinib-mediated apoptosis. Notably, we found that the
      protective effect of SPARC required intracellular retention inside cells.
      Accordingly, SPARC was not secreted into the culture medium of IM-R cells.
      Increased SPARC expression was intimately linked to persistent activation of the
      Fyn/ERK kinase signaling axis. Pharmacologic inhibition of this pathway or siRNA
      mediated knockdown of Fyn kinase resensitized IM-R cells to imatinib. In support
      of our findings, increased levels of SPARC mRNA were documented in blood cells
      from CML patients after 1 year of imatinib therapy compared with initial
      diagnosis. Taken together, our results highlight an important role for the
      Fyn/ERK signaling pathway in imatinib-resistant cells that is driven by
      accumulation of intracellular SPARC.

PMID- 21098701
TI  - Photothermal response of human and murine cancer cells to multiwalled carbon
      nanotubes after laser irradiation.
AB  - This study demonstrates the capability of multiwalled carbon nanotubes (MWNTs)
      coupled with laser irradiation to enhance treatment of cancer cells through
      enhanced and more controlled thermal deposition, increased tumor injury, and
      diminished heat shock protein (HSP) expression. We also explored the potential
      promise of MWNTs as drug delivery agents by observing the degree of intracellular
      uptake of these nanoparticles. To determine the heat generation capability of
      MWNTs, the absorption spectra and temperature rise during heating were measured.
      Higher optical absorption was observed for MWNTs in water compared with water
      alone. For identical laser parameters, MWNT-containing samples produced a
      significantly greater temperature elevation compared to samples treated with
      laser alone. Human prostate cancer (PC3) and murine renal carcinoma (RENCA) cells
      were irradiated with a 1,064-nm laser with an irradiance of 15.3 W/cm(2) for 2
      heating durations (1.5 and 5 minutes) alone or in combination with MWNT
      inclusion. Cytotoxicity and HSP expression following laser heating was used to
      determine the efficacy of laser treatment alone or in combination with MWNTs. No
      toxicity was observed for MWNTs alone. Inclusion of MWNTs dramatically decreased
      cell viability and HSP expression when combined with laser irradiation. MWNT cell
      internalization was measured using fluorescence and transmission electron
      microscopy following incubation of MWNTs with cells. With increasing incubation
      duration, a greater number of MWNTs were observed in cellular vacuoles and
      nuclei. These findings offer an initial proof of concept for the application of
      MWNTs in cancer therapy.

PMID- 21098702
TI  - Multicenter study of the association between betapapillomavirus infection and
      cutaneous squamous cell carcinoma.
AB  - Human papillomaviruses (betaPV) from the beta genus cannot be classified
      according to their oncogenicity due to a paucity of information. This study
      evaluates the association between betaPV infection and cutaneous squamous cell
      carcinoma in conjunction with measures of UV exposure and susceptibility. We
      performed case-control studies in the Netherlands, Italy, and Australia,
      countries with profoundly different UV exposures. The presence of 25 betaPV types
      in eyebrow hair follicles was determined using a highly sensitive HPV DNA
      genotyping assay, and antibodies for the 15 most prevalent betaPV types in a
      total of 689 squamous cell carcinoma cases and 845 controls were detected using
      multiplex serology. Multivariate logistic regression models were used for case
      control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow
      hairs of more than 90% of all participants. The presence of betaPV DNA was
      associated with an increased risk of squamous cell carcinoma in the Netherlands
      (OR = 2.8; 95% CI 1.3-5.8) and Italy (OR = 1.7; 95% CI 0.79-3.6), but not in
      Australia (OR = 0.91; 95% CI 0.53-1.6). Seropositivity for betaPV in controls
      ranged between 52% and 67%. A positive antibody response against 4 or more betaPV
      types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI
      1.4-3.3), the Netherlands (OR = 2.0; 95% CI 1.2-3.4) and fair-skinned Italians
      (OR = 1.6, 95% CI 0.94- 2.7). The association between UV susceptibility and
      squamous cell carcinoma was stronger in betaPV-seropositive people. These
      combined data support the hypothesis that betaPV may play a role in the
      development of cutaneous squamous cell carcinoma.

PMID- 21098703
TI  - Homotypic gap junctional communication associated with metastasis suppression
      increases with PKA activity and is unaffected by PI3K inhibition.
AB  - Loss of gap junctional intercellular communication (GJIC) between cancer cells is
      a common characteristic of malignant transformation. This communication is
      mediated by connexin proteins that make up the functional units of gap junctions.
      Connexins are highly regulated at the protein level and phosphorylation events
      play a key role in their trafficking and degradation. The metastasis suppressor
      breast cancer metastasis suppressor 1 (BRMS1) upregulates GJIC and decreases
      phosphoinositide-3-kinase (PI3K) signaling. On the basis of these observations,
      we set out to determine whether there was a link between PI3K and GJIC in
      tumorigenic and metastatic cell lines. Treatment of cells with the well-known
      PI3K inhibitor LY294002, and its structural analogue LY303511, which does not
      inhibit PI3K, increased homotypic GJIC; however, we found the effect to be
      independent of PI3K/AKT inhibition. We show in multiple cancer cell lines of
      varying metastatic capability that GJIC can be restored without enforced
      expression of a connexin gene. In addition, while levels of connexin 43 remained
      unchanged, its relocalization from the cytosol to the plasma membrane was
      observed. Both LY294002 and LY303511 increased the activity of protein kinase A
      (PKA). Moreover, PKA blockade by the small molecule inhibitor H89 decreased the
      LY294002/LY303511-mediated increase in GJIC. Collectively, our findings show a
      connection between PKA activity and GJIC mediated by PI3K-independent mechanisms
      of LY294002 and LY303511. Manipulation of these signaling pathways could prove
      useful for antimetastatic therapy.

PMID- 21098704
TI  - Combining ATR suppression with oncogenic Ras synergistically increases genomic
      instability, causing synthetic lethality or tumorigenesis in a dosage-dependent
      manner.
AB  - Previous studies indicate that oncogenic stress activates the ATR-Chk1 pathway.
      Here, we show that ATR-Chk1 pathway engagement is essential for limiting genomic
      instability following oncogenic Ras transformation. ATR pathway inhibition in
      combination with oncogenic Ras expression synergistically increased genomic
      instability, as quantified by chromatid breaks, sister chromatid exchanges, and
      H2AX phosphorylation. This level of instability was significantly greater than
      that observed following ATR suppression in untransformed control cells. In
      addition, consistent with a deficiency in long-term genome maintenance,
      hypomorphic ATR pathway reduction to 16% of normal levels was synthetic lethal
      with oncogenic Ras expression in cultured cells. Notably, elevated genomic
      instability and synthetic lethality following suppression of ATR were not due to
      accelerated cycling rates in Ras-transformed cells, indicating that these
      synergistic effects were generated on a per-cell-cycle basis. In contrast to the
      synthetic lethal effects of hypomorphic ATR suppression, subtle reduction of ATR
      expression (haploinsufficiency) in combination with endogenous levels of K
      ras(G12D) expression elevated the incidence of lung adenocarcinoma, spindle cell
      sarcoma, and thymic lymphoma in p53 heterozygous mice. K-ras(G12D)-induced
      tumorigenesis in ATR(+/-)p53(+/-) mice was associated with intrachromosomal
      deletions and loss of wild-type p53. These findings indicate that synergistic
      increases in genomic instability following ATR reduction in oncogenic Ras
      transformed cells can produce 2 distinct biological outcomes: synthetic lethality
      upon significant suppression of ATR expression and tumor promotion in the context
      of ATR haploinsufficiency. These results highlight the importance of the ATR
      pathway both as a barrier to malignant progression and as a potential target for
      cancer treatment.

PMID- 21098705
TI  - p21CIP-1/WAF-1 induction is required to inhibit prostate cancer growth elicited
      by deficient expression of the Wnt inhibitor Dickkopf-1.
AB  - Osteoblastic bone metastases are the most common metastases produced by human
      prostate cancers (PCa). Deregulated activity of Wnt growth factors resulting from
      overexpression of the Wnt inhibitor Dickkopf-1 (DKK-1) is known to contribute to
      formation of the osteoblastic component of PCa skeletal bone metastases. In this
      study, we report that DKK-1 knockdown in osteolytic human PCa cells unexpectedly
      delays the development of both soft tissue and osseous lesions. PCa cells
      deficient in DKK-1 expression did not increase canonical Wnt signaling in target
      osteoblast cell lines; however, DKK-1 knockdown PCa cells exhibited increased
      expression of the CDK inhibitor p21(CIP1/WAF1) and a 32% increase in G(1) arrest
      compared with control cells. Ablating p21(CIP1/WAF1) in PCa cells deficient in
      DKK-1 was sufficient to rescue tumor growth. Collectively, our findings
      demonstrate that DKK-1 overexpression supports tumor growth in part by
      restricting expression of p21(CIP1/WAF1) through a mechanism independent of
      canonical Wnt signaling.

PMID- 21098706
TI  - Gadd45a functions as a promoter or suppressor of breast cancer dependent on the
      oncogenic stress.
AB  - Gadd45a plays a pivotal role as a stress sensor that modulates cellular responses
      to various stress stimuli including oncogenic stress. We reported that the stress
      sensor Gadd45a gene functions as a tumor suppressor in Ras-driven breast
      tumorigenesis via increasing JNK-mediated apoptosis and p38-mediated senescence.
      In contrast, here, we show that Gadd45a promotes Myc-driven breast cancer by
      negatively regulating MMP10 via GSK3 beta/beta-catenin signaling, resulting in
      increased tumor vascularization and growth. These novel findings indicate that
      Gadd45a functions as either tumor promoter or suppressor, is dependent on the
      oncogenic stress, and is mediated via distinct signaling pathways. Collectively,
      these novel findings highlight the significance of the type of oncogenic
      alteration on how stress response genes function during initiation and
      progression of tumorigenesis. Because Gadd45a is a target for BRCA1 and p53,
      these findings have implications regarding BRCA1/p53 tumor suppressor functions.

PMID- 21098707
TI  - HER2 silences tumor suppression in breast cancer cells by switching expression of
      C/EBPbeta isoforms.
AB  - Tumor progression requires ablation of suppressor functions mediated by
      transforming growth factor beta (TGFbeta) signaling and by oncogene-induced
      senescence (OIS), but how these functions are canceled in specific subtypes of
      breast cancer remains unknown. In this study, we show that HER2-overexpressing
      breast cancer cells avert TGFbeta- and OIS-mediated tumor suppression by
      switching expression of 2 functionally distinct isoforms of the transcription
      factor C/EBPbeta, which has been implicated previously in breast cancer
      development. HER2 signaling activates the translational regulatory factor CUGBP1,
      which favors the production of the transcriptionally inhibitory isoform LIP over
      that of the active isoform LAP. LIP overexpression prevents the assembly of
      LAP/Smad transcriptional repressor complexes on the MYC promoter in response to
      TGFbeta, and interferes with activation of OIS responses. Treatment of HER2
      transformed mammary epithelial cells with the HER2 antibody trastuzumab reduces
      LIP levels, restoring these suppressor responses. Our findings reveal a novel
      mechanism through which HER2 silences tumor suppression in a concerted manner,
      contributing to the potency of this oncogene in breast cancer.

PMID- 21098708
TI  - A novel signaling axis of matriptase/PDGF-D/beta-PDGFR in human prostate cancer.
AB  - Increasing evidence indicates the significance of platelet-derived growth factor
      receptor-beta (beta-PDGFR) signaling in prostate cancer (PCa). Accordingly,
      preclinical studies suggest the potential of beta-PDGFR as a therapeutic target
      in metastatic PCa. However, a ligand responsible for beta-PDGFR activation in PCa
      was unknown, and recent clinical trials with imatinib mesylate showed limited
      success due to normal tissue toxicity. Similarly, in spite of mounting evidence
      indicating the significance of matriptase in PCa, little is known about its
      substrates or molecular actions during PCa progression. Here, we identified PDGF
      D as a ligand for beta-PDGFR in PCa and discovered matriptase as its regulator.
      Matriptase activates PDGF-D by proteolytic removal of the CUB domain in a 2-step
      process, creating a hemidimer, followed by growth factor domain dimer (GFD-D)
      generation. Matriptase can deactivate PDGF-D by further proteolytic cleavage
      within the GFD, revealing its biphasic regulation. Importantly, PDGF-D/matriptase
      colocalization is accompanied with beta-PDGFR phosphorylation in human PCa
      tissues. This study unveiled a novel signaling axis of matriptase/PDGF-D/beta
      PDGFR in PCa, providing new insights into functional interplay between serine
      protease and growth factor signaling networks.

PMID- 21098709
TI  - Negative regulation of p53 by the long isoform of ErbB3 binding protein Ebp1 in
      brain tumors.
AB  - The ErbB3 binding protein Ebp1 has been implicated in a number of human cancers.
      Ebp1 includes 2 isoforms, p48 and p42, that exhibit different cellular
      activities. Here we show that the larger p48 isoform is transforming and that it
      promotes cell growth, clonogenicity, and invasion in human glioblastoma (GBM).
      P48 overexpression in GBM cells facilitated tumorigenesis and enhanced tumor
      growth in mouse xenograft models. Human GBM tissues displayed elevated levels of
      p48 compared with surrounding normal tissues or low-grade tumors. Notably, p48
      levels were inversely correlated with poor prognosis in GBM patients. We
      determined that p48 binds to the p53 E3 ligase HDM2, enhancing HDM2-p53
      association and thereby promoting p53 polyubiquitination and degradation to
      reduce steady-state p53 levels and activity. Together, our findings suggest that
      p48 functions as an oncogene by promoting glioma tumorigenicity via interactions
      with HDM2 that contribute to p53 downregulation.

PMID- 21098710
TI  - Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis
      of HBV-positive hepatocarcinoma.
AB  - Diagnosis of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC),
      particularly HCC independent of cirrhosis etiology, presents a great challenge
      because of a lack of biomarkers. Here we test the hypothesis that expression
      profiles of microRNAs (miRNAs) in serum can serve as biomarkers for diagnosis of
      HBV infection and HBV-positive HCC. We recruited 513 subjects (210 controls and
      135 HBV-, 48 hepatitis C virus (HCV)-, and 120 HCC-affected individuals) and
      employed a strategy of initial screening by Solexa sequencing followed by
      validation with TaqMan probe-based quantitative reverse transcription-PCR assay.
      First, because of a close link between chronic hepatitis B and HCC, we compared
      miRNA expression profiles in HBV serum with that in control serum and
      successfully obtained 13 miRNAs that were differentially expressed in HBV serum.
      This 13-miRNA-based biomarker accurately discriminated not only HBV cases from
      controls and HCV cases, but also HBV-positive HCC cases from control and HBV
      cases. Second, we directly compared miRNA expressions in HCC serum with those in
      controls and identified 6 miRNAs that were significantly upregulated in HCC
      samples. Interestingly, 2 of these miRNAs, miR-375 and miR-92a, were also
      identified by our first approach as HBV specific. When we employed 3 of these
      miRNAs (miR-25, miR-375, and let-7f) as biomarkers, we could clearly separate HCC
      cases from controls, and miR-375 alone had an ROC of 0.96 (specificity: 96%;
      sensitivity: 100%) in HCC prediction. In conclusion, our study demonstrates for
      the first time that serum miRNA profiles can serve as novel and noninvasive
      biomarkers for HBV infection and HBV-positive HCC diagnosis.

PMID- 21098711
TI  - An ex(o)citing machinery for invasive tumor growth.
AB  - Cancer cells communicate with the environment through delivery of surface
      proteins, release of soluble factors (growth factors and cytokines), and
      sophisticated nanovehicles (exosomes) for establishment of invasive tumor growth.
      This communication occurs in part through constitutive exocytosis, regulated
      exocytosis, or release of intraluminal vesicles, and is modulated by small Rab
      GTPases, the master regulators of vesicle traffic. We studied Rab GTPases
      implicated in regulated exocytosis and showed a unique role for Rab27B in
      invasive tumor growth. Emerging evidence indicates that various exocytic routes
      are implemented by cancer cells to relay crucial information for fostering
      growth, migration, and matrix degradation.

PMID- 21098713
TI  - Integration of host-related signatures with cancer cell-derived predictors for
      the optimal management of anticancer chemotherapy.
AB  - Current cancer management aims to integrate molecular signatures into the design
      of personalized therapies. Recent advances in "omics" done on tumor specimens
      have led to the identification of factors that either recognize cancers of dismal
      prognosis or pinpoint "druggable" signaling pathways, which can be interrupted by
      targeted therapies. However, accumulating evidence underscores the biological and
      clinical significance of immune predictors in several compartments (blood, serum,
      tumor) in a variety of malignancies. An additional aspect that has been
      overlooked is the bidirectional, tumor-host interaction during therapeutic
      intervention, suggesting that dynamic molecular, biochemical, and metabolic
      signatures should be developed in the future. We review immune parameters of
      prognostic or predictive value during cancer therapy, and highlight existing
      "descriptive-prognostic" and "functional-therapeutic" molecular signatures, with
      the hindsight of designing appropriate compensatory therapies.

PMID- 21098712
TI  - Cancer exosomes trigger fibroblast to myofibroblast differentiation.
AB  - There is a growing interest in the cell-cell communication roles in cancer
      mediated by secreted vesicles termed exosomes. In this study, we examined whether
      exosomes produced by cancer cells could transmit information to normal stromal
      fibroblasts and trigger a cellular response. We found that some cancer-derived
      exosomes could trigger elevated alpha-smooth muscle actin expression and other
      changes consistent with the process of fibroblast differentiation into
      myofibroblasts. We show that TGF-beta is expressed at the exosome surface in
      association with the transmembrane proteoglycan betaglycan. Although existing in
      a latent state, this complex was fully functional in eliciting SMAD-dependent
      signaling. Inhibiting either signaling or betaglycan expression attenuated
      differentiation. While the kinetics and overall magnitude of the response were
      similar to that achieved with soluble TGF-beta, we identified important
      qualitative differences unique to the exosomal route of TGF-beta delivery, as
      exemplified by a significant elevation in fibroblast FGF2 production. This
      hitherto unknown trigger for instigating cellular differentiation in a
      distinctive manner has major implications for mechanisms underlying cancer
      recruited stroma, fibrotic diseases, and wound-healing responses.

PMID- 21098714
TI  - Melanoma cells express ICOS ligand to promote the activation and expansion of T
      regulatory cells.
AB  - CD4(+)CD25(+)Foxp3(+) T-regulatory cells (Tregs) accumulate in tumors; however,
      little is known about how the tumor environment influences this process. Here we
      show that human melanomas express inducible T-cell costimulator ligand (ICOS
      L/B7H) that can provide costimulation through ICOS for the expansion of activated
      Tregs maintaining high Foxp3 and CD25 expression as well as a suppressive
      function. Thus, ICOS-L expression by melanoma tumor cells may directly drive Treg
      activation and expansion in the tumor microenvironment as another mechanism of
      immune evasion.

PMID- 21098715
TI  - Tumor ablation by gene-modified T cells in the absence of autoimmunity.
AB  - Adoptive immunotherapy involving genetic modification of T cells with antigen
      specific, chimeric, single-chain receptors is a promising approach for the
      treatment of cancer. To determine whether gene-modified T cells could induce
      antitumor effects without associated autoimmune pathology, we assessed the
      ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate tumor
      in Her-2 transgenic mice that express human Her-2 as a self-antigen in brain and
      mammary tissues. In adoptive transfer studies, we demonstrated significant
      improvement in the survival of mice bearing Her-2(+) 24JK tumor following
      administration of anti-Her-2 T cells compared with control T cells. The
      incorporation of a lymphoablative step prior to adoptive transfer of anti-Her-2 T
      cells and administration of IL-2 were both found to further enhance survival. The
      reduction in tumor growth was also correlated with localization of transferred T
      cells at the tumor site. Furthermore, an antigen-specific recall response could
      be induced in long-term surviving mice following rechallenge with Her-2(+) tumor.
      Importantly, antitumor effects were not associated with any autoimmune pathology
      in normal tissue expressing Her-2 antigen. This study highlights the therapeutic
      potential of using gene-engineered T cells as a safe and effective treatment of
      cancer.

PMID- 21098716
TI  - Endothelial cell-initiated signaling promotes the survival and self-renewal of
      cancer stem cells.
AB  - Recent studies have demonstrated that cancer stem cells play an important role in
      the pathobiology of head and neck squamous cell carcinomas (HNSCC). However,
      little is known about functional interactions between head and neck cancer stem
      like cells (CSC) and surrounding stromal cells. Here, we used aldehyde
      dehydrogenase activity and CD44 expression to sort putative stem cells from
      primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin-) led to tumors in
      13 (out of 15) mice, whereas 10,000 noncancer stem cells (ALDH-CD44-Lin-)
      resulted in 2 tumors in 15 mice. These data demonstrated that ALDH and CD44
      select a subpopulation of cells that are highly tumorigenic. The ability to self
      renew was confirmed by the observation that ALDH+CD44+Lin- cells sorted from
      human HNSCC formed more spheroids (orospheres) in 3-D agarose matrices or ultra
      low attachment plates than controls and were serially passaged in vivo. We
      observed that approximately 80% of the CSC were located in close proximity
      (within 100-MUm radius) of blood vessels in human tumors, suggesting the
      existence of perivascular niches in HNSCC. In vitro studies demonstrated that
      endothelial cell-secreted factors promoted self-renewal of CSC, as demonstrated
      by the upregulation of Bmi-1 expression and the increase in the number of
      orospheres as compared with controls. Notably, selective ablation of tumor
      associated endothelial cells stably transduced with a caspase-based artificial
      death switch (iCaspase-9) caused a marked reduction in the fraction of CSC in
      xenograft tumors. Collectively, these findings indicate that endothelial cell
      initiated signaling can enhance the survival and self-renewal of head and neck
      CSC.

PMID- 21098717
TI  - A novel interaction between hedgehog and Notch promotes proliferation at the
      anterior-posterior organizer of the Drosophila wing.
AB  - Notch has multiple roles in the development of the Drosophila melanogaster wing
      imaginal disc. It helps specify the dorsal-ventral compartment border, and it is
      needed for the wing margin, veins, and sensory organs. Here we present evidence
      for a new role: stimulating growth in response to Hedgehog. We show that Notch
      signaling is activated in the cells of the anterior-posterior organizer that
      produce the region between wing veins 3 and 4, and we describe strong genetic
      interactions between the gene that encodes the Hedgehog pathway activator
      Smoothened and the Notch pathway genes Notch, presenilin, and Suppressor of
      Hairless and the Enhancer of split complex. This work thus reveals a novel
      collaboration by the Hedgehog and Notch pathways that regulates proliferation in
      the 3-4 intervein region independently of Decapentaplegic.

PMID- 21098718
TI  - Important characteristics of sequence-specific recombination hotspots in
      Schizosaccharomyces pombe.
AB  - In many organisms, meiotic recombination occurs preferentially at a limited
      number of sites in the genome known as hotspots. In the fission yeast
      Schizosaccharomyces pombe, simple sequence motifs determine the location of at
      least some, and possibly most or all, hotspots. Recently, we showed that a large
      number of different sequences can create hotspots. Among those sequences we
      identified some recurring motifs that fell into at least five distinct families,
      including the well-characterized CRE family of hotspots. Here we report the
      essential sequence for activity of two of the novel hotspots, the oligo-C and
      CCAAT hotspots, and identify associated trans-acting factors required for hotspot
      activity. The oligo-C hotspot requires a unique 8-bp sequence, CCCCGCAC, though
      hotspot activity is also significantly affected by adjacent nucleotides. The
      CCAAT hotspot requires a more complex and degenerate sequence, including the
      originally identified seven nucleotide CCAATCA sequence at its core. We
      identified transcription factors, the CCAAT-binding factor (CBF) and Rst2, which
      are required specifically for activity of the CCAAT hotspots and oligo-C
      hotspots, respectively. Each of these factors binds to its respective motifs in
      vitro. However, unlike CRE, the sequence required for hotspot activity is larger
      than the sequence required for binding, suggesting the involvement of additional
      factors.

PMID- 21098719
TI  - Inferences about the distribution of dominance drawn from yeast gene knockout
      data.
AB  - Data from several thousand knockout mutations in yeast (Saccharomyces cerevisiae)
      were used to estimate the distribution of dominance coefficients. We propose a
      new unbiased likelihood approach to measuring dominance coefficients. On average,
      deleterious mutations are partially recessive, with a mean dominance coefficient
      ~0.2. Alleles with large homozygous effects are more likely to be more recessive
      than are alleles of weaker effect. Our approach allows us to quantify, for the
      first time, the substantial variance and skew in the distribution of dominance
      coefficients. This heterogeneity is so great that many population genetic
      processes analyses based on the mean dominance coefficient alone will be in
      substantial error. These results are applied to the debate about various
      mechanisms for the evolution of dominance, and we conclude that they are most
      consistent with models that depend on indirect selection on homeostatic gene
      expression or on the ability to perform well under periods of high demand for a
      protein.

PMID- 21098720
TI  - Control of germline torso expression by the BTB/POZ domain protein pipsqueak is
      required for embryonic terminal patterning in Drosophila.
AB  - Early embryogenesis in Drosophila melanogaster is controlled by maternal gene
      products, which are deposited in the egg during oogenesis. It is not well
      understood how maternal gene expression is controlled during germline
      development. pipsqueak (psq) is a complex locus that encodes several nuclear
      protein variants containing a PSQ DNA-binding domain and a BTB/POZ domain. Psq
      proteins are thought to regulate germline gene expression through epigenetic
      silencing. While psq was originally identified as a posterior-group gene, we show
      here a novel role of psq in embryonic terminal patterning. We characterized a new
      psq loss-of-function allele, psq(rum), which specifically affects signaling by
      the Torso (Tor) receptor tyrosine kinase (RTK). Using genetic epistasis, gene
      expression analyses, and rescue experiments, we demonstrate that the sole
      function impaired by the psq(rum) mutation in the terminal system is an essential
      requirement for controlling transcription of the tor gene in the germline. In
      contrast, the expression of several other maternal genes, including those
      encoding Tor pathway components, is not affected by the mutation. Rescue of the
      psq(rum) terminal phenotype does not require the BTB/POZ domain, suggesting that
      the PSQ DNA-binding domain can function independently of the BTB/POZ domain. Our
      finding that tor expression is subject to dedicated transcriptional regulation
      suggests that different maternal genes may be regulated by multiple distinct
      mechanisms, rather than by a general program controlling nurse-cell
      transcription.

PMID- 21098721
TI  - Changes in selective effects over time facilitate turnover of enhancer sequences.
AB  - Correct gene expression is often critical and consequently stabilizing selection
      on expression is widespread. Yet few genes possess highly conserved regulatory
      DNA, and for the few enhancers that have been carefully characterized,
      substantial functional reorganization has often occurred. Given that natural
      selection removes mutations of even very small deleterious effect, how can
      transcription factor binding evolve so readily when it underlies a conserved
      phenotype? As a first step toward addressing this question, I combine a
      computational model for regulatory function that incorporates many aspects of our
      present biological knowledge with a model for the fitness effects of
      misexpression. I then use this model to study the evolution of enhancers. Several
      robust behaviors emerge: First, the selective effects of mutations at a site
      change dramatically over time due to substitutions elsewhere in the enhancer, and
      even the overall degree of constraint across the enhancer can change
      considerably. Second, many of the substitutions responsible for changes in
      binding occur at sites where previously the mutation would have been strongly
      deleterious, suggesting that fluctuations in selective effects at a site are
      important for functional turnover. Third, most substitutions contributing to the
      repatterning of binding and constraint are effectively neutral, highlighting the
      importance of genetic drift-even for enhancers underlying conserved phenotypes.
      These findings have important implications for phylogenetic inference of function
      and for interpretations of selection coefficients estimated for regulatory DNA.

PMID- 21098722
TI  - Genetic evidence for antagonism between Pak protein kinase and Rho1 small GTPase
      signaling in regulation of the actin cytoskeleton during Drosophila oogenesis.
AB  - During Drosophila oogenesis, basally localized F-actin bundles in the follicle
      cells covering the egg chamber drive its elongation along the anterior-posterior
      axis. The basal F-actin of the follicle cell is an attractive system for the
      genetic analysis of the regulation of the actin cytoskeleton, and results
      obtained in this system are likely to be broadly applicable in understanding
      tissue remodeling. Mutations in a number of genes, including that encoding the
      p21-activated kinase Pak, have been shown to disrupt organization of the basal F
      actin and in turn affect egg chamber elongation. pak mutant egg chambers have
      disorganized F-actin distribution and remain spherical due to a failure to
      elongate. In a genetic screen to identify modifiers of the pak rounded egg
      chamber phenotype several second chromosome deficiencies were identified as
      suppressors. One suppressing deficiency removes the rho1 locus, and we determined
      using several rho1 alleles that removal of a single copy of rho1 can suppress the
      pak phenotype. Reduction of any component of the Rho1-activated actomyosin
      contractility pathway suppresses pak oogenesis defects, suggesting that Pak
      counteracts Rho1 signaling. There is ectopic myosin light chain phosphorylation
      in pak mutant follicle cell clones in elongating egg chambers, probably due at
      least in part to mislocalization of RhoGEF2, an activator of the Rho1 pathway. In
      early egg chambers, pak mutant follicle cells have reduced levels of myosin
      phosphorylation and we conclude that Pak both promotes and restricts myosin light
      chain phosphorylation in a temporally distinct manner during oogenesis.

PMID- 21098723
TI  - The putative lipid transporter, Arv1, is required for activating pheromone
      induced MAP kinase signaling in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae haploid cells respond to extrinsic mating signals by
      forming polarized projections (shmoos), which are necessary for conjugation. We
      have examined the role of the putative lipid transporter, Arv1, in yeast mating,
      particularly the conserved Arv1 homology domain (AHD) within Arv1 and its role in
      this process. Previously it was shown that arv1 cells harbor defects in
      sphingolipid and glycosylphosphatidylinositol (GPI) biosyntheses and may harbor
      sterol trafficking defects. Here we demonstrate that arv1 cells are mating
      defective and cannot form shmoos. They lack the ability to initiate pheromone
      induced G1 cell cycle arrest, due to failure to polarize PI(4,5)P(2) and the Ste5
      scaffold, which results in weakened MAP kinase signaling activity. A mutant Ste5,
      Ste5(Q59L), which binds more tightly to the plasma membrane, suppresses the MAP
      kinase signaling defects of arv1 cells. Filipin staining shows arv1 cells contain
      altered levels of various sterol microdomains that persist throughout the mating
      process. Data suggest that the sterol trafficking defects of arv1 affect
      PI(4,5)P(2) polarization, which causes a mislocalization of Ste5, resulting in
      defective MAP kinase signaling and the inability to mate. Importantly, our
      studies show that the AHD of Arv1 is required for mating, pheromone-induced G1
      cell cycle arrest, and for sterol trafficking.

PMID- 21098724
TI  - Enhancement of proteasome function by PA28&alpha; overexpression protects against
      oxidative stress.
AB  - The principal function of the proteasome is targeted degradation of intracellular
      proteins. Proteasome dysfunction has been observed in experimental
      cardiomyopathies and implicated in human congestive heart failure. Measures to
      enhance proteasome proteolytic function are currently lacking but would be
      beneficial in testing the pathogenic role of proteasome dysfunction and could
      have significant therapeutic potential. The association of proteasome activator
      28 (PA28) with the 20S proteasome may play a role in antigen processing. It is
      unclear, however, whether the PA28 plays any important role outside of antigen
      presentation, although up-regulation of PA28 has been observed in certain types
      of cardiomyopathy. Here, we show that PA28alpha overexpression (PA28alphaOE)
      stabilized PA28beta, increased 11S proteasomes, and enhanced the degradation of a
      previously validated proteasome surrogate substrate (GFPu) in cultured neonatal
      rat cardiomyocytes. PA28alphaOE significantly attenuated H(2)O(2)-induced
      increases in the protein carbonyls and markedly suppressed apoptosis in cultured
      cardiomyocytes under basal conditions or when stressed by H(2)O(2). We conclude
      that PA28alphaOE is sufficient to up-regulate 11S proteasomes, enhance proteasome
      mediated removal of misfolded and oxidized proteins, and protect against
      oxidative stress in cardiomyocytes, providing a highly sought means to increase
      proteasomal degradation of abnormal cellular proteins.

PMID- 21098725
TI  - STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by
      sirtuin 1 through a direct inhibition of STAT3 acetylation.
AB  - IL-22 has a pathogenetic role in psoriasis, where it is responsible for the
      altered proliferation and differentiation of keratinocytes and induces
      inflammatory molecules. The IL-22-induced effects are mediated by STAT3, whose
      activity is proportional to acetylation in lysine (Lys)685 and phosphorylation in
      tyrosine (Tyr)705. Lys 685 acetylation of STAT3 is inhibited by sirtuin (SIRT)1,
      a class III deacetylase promoting keratinocyte differentiation. Due to the
      opposite effects of IL-22 and SIRT1, we investigated whether IL-22-induced
      effects in keratinocytes could be regulated by SIRT1 through control of STAT3. We
      found that SIRT1 opposes the IL-22-induced STAT3 activity by deacetylating STAT3
      and reducing STAT3 Tyr705 phosphorylation. By controlling STAT3, SIRT1 also
      influences the IL-22-induced expression of molecules involved in proliferation
      and inflammation as well as proliferation and migration processes in cultured
      keratinocytes. Although SIRT1 levels were similar in keratinocytes of healthy
      individuals and patients with psoriasis, they were reduced in psoriatic skin
      lesions, with the lymphokine IFN-gamma inhibiting SIRT1 expression.
      Concomitantly, IFN-gamma enhanced basal acetylation of STAT3 and its
      phosphorylation induced by IL-22. In conclusion, STAT3-dependent IL-22 signaling
      and effects in keratinocytes are negatively regulated by SIRT1. In skin affected
      by psoriasis, SIRT1 is down-regulated by IFN-gamma, which thus renders psoriatic
      keratinocytes more prone to respond to IL-22.

PMID- 21098726
TI  - Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products.
AB  - 5-Lipoxygenase (5-LO) is the essential enzyme for the biosynthesis of
      leukotrienes, important mediators of inflammation. This study investigated
      whether variants of 5-LO exist in human leukocytes. 5-LO mRNA isoforms that are
      consistent with alternative splicing were identified by RT-PCR in a cell line or
      cell type-specific pattern. All evaluated cells expressed mRNA containing all 14
      exons of 5-LO with the expected splicing sites. Individual isoforms that retained
      intron 10 (alpha-10), lacked exon 13 (Delta-13), and lacked exons 10 and 13
      (Delta-10,13) or that lacked the first 96 base pairs of exon 10 (Delta-p10) were
      identified. Immunoreactive bands coeluting with the cloned alpha-10 and Delta-13
      isoforms were measured in primary neutrophils and in Raji cells. When expressed
      in HEK293 cells, alternative proteins were without catalytic activity. However,
      when coexpressed with the active full-length 5-LO, alternative isoforms
      significantly decreased the biosynthesis of 5-LO products by up to 44%, as
      assessed by reverse-phase HPLC analysis. Additionally, in stimulated neutrophils
      the full-length active 5-LO was detected by immunoblot in both nuclear and non
      nuclear compartments, while the Delta-13 isoform was only detected in the nuclear
      fraction. These alternative 5-LO isoforms may represent a new mechanism for the
      regulation of the 5-LO pathway and lipid mediator biosynthesis.

PMID- 21098727
TI  - Cyclic-di-GMP reaches out into the bacterial RNA world.
AB  - The ubiquitous bacterial signaling molecule bis-(3'-5')-cyclic guanosine
      monophosphate (c-di-GMP) has brought second messenger signaling back onto the
      agenda of molecular microbiologists. This is due not only to its general role in
      promoting biofilm formation, but also to the increasingly diverse array of
      effector molecules bound by c-di-GMP and of the target processes affected.
      Effectors include diverse transcription factors and proteins that directly
      interact with complex cellular machineries, as well as RNA molecules that act as
      riboswitches to regulate transcriptional elongation or translation. This
      flexibility in c-di-GMP action enables it to control diverse molecular processes
      in bacterial cells. New evidence further extends this range to include a c-di-GMP
      riboswitch linked to a self-splicing intron that has been "domesticated" by its
      carrier, the pathogenic bacterium Clostridium difficile, to serve in the control
      of expression of a downstream gene.

PMID- 21098728
TI  - BRAF gene amplification can promote acquired resistance to MEK inhibitors in
      cancer cells harboring the BRAF V600E mutation.
AB  - Oncogenic BRAF mutations are found in several tumor types, including melanomas
      and colorectal cancers. Tumors with BRAF mutations have increased mitogen
      activated protein kinase pathway activity and heightened sensitivity to BRAF and
      MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)
      inhibitors. To identify potential mechanisms of acquired drug resistance, we
      generated clones resistant to the allosteric MEK inhibitor AZD6244 from two BRAF
      V600E mutant colorectal cancer cell lines that are highly sensitive to MEK or
      BRAF inhibition. These AZD6244-resistant (AR) clones, which exhibited cross
      resistance to BRAF inhibitors, acquired resistance through amplification of the
      BRAF gene. A small percentage of treatment-naive parental cells showed
      preexisting BRAF amplification. We observed similar amplification in a subset of
      cells in a BRAF-mutant colorectal cancer. In cell lines, BRAF amplification
      increased the abundance of phosphorylated MEK and impaired the ability of AZD6244
      to inhibit ERK (extracellular signal-regulated kinase) phosphorylation. The
      ability of AZD6244 to inhibit ERK phosphorylation in AR cells was restored by
      treatment with a BRAF inhibitor at low concentrations that reduced the abundance
      of phosphorylated MEK to amounts observed in parental cells. Combined MEK and
      BRAF inhibition fully overcame resistance to MEK or BRAF inhibitors alone and was
      also more effective in parental cells compared to treatment with either inhibitor
      alone. These findings implicate BRAF amplification as a mechanism of resistance
      to both MEK and BRAF inhibitors and suggest combined MEK and BRAF inhibition as a
      clinical strategy to overcome, or possibly prevent, this mechanism of resistance.

PMID- 21098729
TI  - HLA class I molecules partner with integrin beta4 to stimulate endothelial cell
      proliferation and migration.
AB  - Among transplant recipients, those who produce antibodies against the donor's
      human leukocyte antigens (HLAs) are at higher risk for antibody-mediated
      rejection and transplant vasculopathy, which is a progressive, vasculo-occlusive
      disease that results in ischemic injury and deterioration of organ function.
      Antibodies against HLA class I (HLA-I) molecules are thought to contribute to
      transplant vasculopathy by triggering signals that elicit the activation and
      proliferation of endothelial cells. Here, we demonstrate a molecular association
      between HLA-I and the integrin beta(4) subunit after the stimulation of
      endothelial cells with HLA-I-specific antibodies. Knockdown of integrin beta(4)
      in these cells abrogated the ability of HLA-I to stimulate the phosphorylation of
      the kinases Akt, extracellular signal-regulated kinase (ERK), and Src, as well as
      cellular proliferation. Similarly, reducing the abundance of HLA-I suppressed
      integrin beta(4)-mediated phosphorylation of ERK and the migration of endothelial
      cells on laminin-5, a component of the extracellular matrix. These results
      indicate a mutual dependency between HLA-I and the integrin beta(4) subunit to
      stimulate the proliferation and migration of endothelial cells, which may be
      important in promoting transplant vasculopathy and tumor angiogenesis.

PMID- 21098730
TI  - The role of the Arabidopsis morning loop components CCA1, LHY, PRR7, and PRR9 in
      temperature compensation.
AB  - A defining, yet poorly understood characteristic of the circadian clock is that
      it is buffered against changes in temperature such that the period length is
      relatively constant across a range of physiologically relevant temperatures. We
      describe here the role of PSEUDO RESPONSE REGULATOR7 (PRR7) and PRR9 in
      temperature compensation. The Arabidopsis thaliana circadian oscillator comprises
      a series of interlocking feedback loops, and PRR7 and PRR9 function in the
      morning loop. The prr7 prr9 double mutant displays a unique phenotype that has
      not been observed before in other Arabidopsis clock mutants. In the prr7 prr9
      mutant, the effects of temperature are overcompensated, apparently due to
      hyperactivation of the transcription factors CIRCADIAN CLOCK ASSOCIATED1 (CCA1)
      and LATE ELONGATED HYPOCOTYL (LHY). Inactivation of CCA1 and LHY fully suppresses
      the overcompensation defects of prr7 prr9 mutants and rescues their long period
      phenotype. Overcompensation in prr7 prr9 mutants does not rely on FLOWERING LOCUS
      C, a previously identified gene required for temperature compensation. Together,
      our results reveal a role of PRR7 and PRR9 in regulating CCA1 and LHY activities
      in response to ambient temperature.

PMID- 21098732
TI  - Temperature compensation of the circadian clock: a role for the morning loop.

PMID- 21098731
TI  - Arabidopsis FIMBRIN5, an actin bundling factor, is required for pollen
      germination and pollen tube growth.
AB  - Actin cables in pollen tubes serve as molecular tracks for cytoplasmic streaming
      and organelle movement and are formed by actin bundling factors like villins and
      fimbrins. However, the precise mechanisms by which actin cables are generated and
      maintained remain largely unknown. Fimbrins comprise a family of five members in
      Arabidopsis thaliana. Here, we characterized a fimbrin isoform, Arabidopsis
      FIMBRIN5 (FIM5). Our results show that FIM5 is required for the organization of
      actin cytoskeleton in pollen grains and pollen tubes, and FIM5 loss-of-function
      associates with a delay of pollen germination and inhibition of pollen tube
      growth. FIM5 decorates actin filaments throughout pollen grains and tubes. Actin
      filaments become redistributed in fim5 pollen grains and disorganized in fim5
      pollen tubes. Specifically, actin cables protrude into the extreme tips, and
      their longitudinal arrangement is disrupted in the shank of fim5 pollen tubes.
      Consequently, the pattern and velocity of cytoplasmic streaming were altered in
      fim5 pollen tubes. Additionally, loss of FIM5 function rendered pollen
      germination and tube growth hypersensitive to the actin-depolymerizing drug
      latrunculin B. In vitro biochemical analyses indicated that FIM5 exhibits actin
      bundling activity and stabilizes actin filaments. Thus, we propose that FIM5
      regulates actin dynamics and organization during pollen germination and tube
      growth via stabilizing actin filaments and organizing them into higher-order
      structures.

PMID- 21098733
TI  - A rice gid1 suppressor mutant reveals that gibberellin is not always required for
      interaction between its receptor, GID1, and DELLA proteins.
AB  - To investigate gibberellin (GA) signaling using the rice (Oryza sativa) GA
      receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) mutant gid1-8, we isolated a
      suppressor mutant, Suppressor of gid1-1 (Sgd-1). Sgd-1 is an intragenic mutant
      containing the original gid1-8 mutation (L45F) and an additional amino acid
      substitution (P99S) in the loop region. GID1(P99S) interacts with the rice DELLA
      protein SLENDER RICE1 (SLR1), even in the absence of GA. Substitution of the 99th
      Pro with other amino acids revealed that substitution with Ala (P99A) caused the
      highest level of GA-independent interaction. Physicochemical analysis using
      surface plasmon resonance revealed that GID1(P99A) has smaller K(a) (association)
      and K(d) (dissociation) values for GA(4) than does wild-type GID1. This suggests
      that the GID1(P99A) lid is at least partially closed, resulting in both GA
      independent and GA-hypersensitive interactions with SLR1. One of the three
      Arabidopsis thaliana GID1s, At GID1b, can also interact with DELLA proteins in
      the absence of GA, so we investigated whether GA-independent interaction of At
      GID1b depends on a mechanism similar to that of rice GID1(P99A). Substitution of
      the loop region or a few amino acids of At GID1b with those of At GID1a
      diminished its GA-independent interaction with GAI while maintaining the GA
      dependent interaction. Soybean (Glycine max) and Brassica napus also have GID1s
      similar to At GID1b, indicating that these unique GID1s occur in various dicots
      and may have important functions in these plants.

PMID- 21098734
TI  - Rice xa13 recessive resistance to bacterial blight is defeated by induction of
      the disease susceptibility gene Os-11N3.
AB  - The rice (Oryza sativa) gene xa13 is a recessive resistance allele of Os-8N3, a
      member of the NODULIN3 (N3) gene family, located on rice chromosome 8. Os-8N3 is
      a susceptibility (S) gene for Xanthomonas oryzae pv oryzae, the causal agent of
      bacterial blight, and the recessive allele is defeated by strains of the pathogen
      producing any one of the type III effectors AvrXa7, PthXo2, or PthXo3, which are
      all members of the transcription activator-like (TAL) effector family. Both
      AvrXa7 and PthXo3 induce the expression of a second member of the N3 gene family,
      here named Os-11N3. Insertional mutagenesis or RNA-mediated silencing of Os-11N3
      resulted in plants with loss of susceptibility specifically to strains of X.
      oryzae pv oryzae dependent on AvrXa7 or PthXo3 for virulence. We further show
      that AvrXa7 drives expression of Os-11N3 and that AvrXa7 interacts and binds
      specifically to an effector binding element within the Os-11N3 promoter, lending
      support to the predictive models for TAL effector binding specificity. The result
      indicates that variations in the TAL effector repetitive domains are driven by
      selection to overcome both dominant and recessive forms of resistance to
      bacterial blight in rice. The finding that Os-8N3 and Os-11N3 encode closely
      related proteins also provides evidence that N3 proteins have a specific function
      in facilitating bacterial blight disease.

PMID- 21098735
TI  - The MAP kinase MPK4 is required for cytokinesis in Arabidopsis thaliana.
AB  - Cytokinesis in plants is achieved by the formation of the cell plate. A pathway
      that includes mitogen-activated protein (MAP) kinase kinase kinase and MAP kinase
      kinase (MAPKK) plays a key role in the control of plant cytokinesis. We show here
      that a MAP kinase, MPK4, is required for the formation of the cell plate in
      Arabidopsis thaliana. Single mutations in MPK4 caused dwarfism and characteristic
      defects in cytokinesis, such as immature cell plates, which became much more
      prominent upon introduction of a mutation in MKK6/ANQ, the MAPKK for cytokinesis,
      into mpk4. MKK6/ANQ strongly activated MPK4 in protoplasts, and kinase activity
      of MPK4 was detected in wild-type tissues that contained dividing cells but not
      in mkk6/anq mutants. Fluorescent protein-fused MPK4 localized to the expanding
      cell plates in cells of root tips. Expansion of the cell plates in mpk4 root tips
      appeared to be retarded. The level of MPK11 transcripts was markedly elevated in
      mpk4 plants, and defects in the mpk4 mpk11 double mutant with respect to growth
      and cytokinesis were more severe than in the corresponding single mutants. These
      results indicate that MPK4 is the downstream target of MKK6/ANQ in the regulation
      of cytokinesis in Arabidopsis and that MPK11 is also involved in cytokinesis.

PMID- 21098736
TI  - Effect of exercise intensity and AICAR on isoform-specific expressions of murine
      skeletal muscle PGC-1alpha mRNA: a role of beta2-adrenergic receptor activation.
AB  - There are three isoforms of peroxisome proliferator-activated receptor-gamma
      coactivator 1alpha (PGC-1alpha) mRNA, which promotes mitochondrial biogenesis in
      skeletal muscles. Compared with PGC-1alpha-a mRNA, PGC-1alpha-b or PGC-1alpha-c
      mRNA is transcribed by a different exon 1 of the PGC-1alpha gene. In this study,
      effects of exercise intensity and 5-aminoimidazole-4-carboxamide-1beta-d
      ribofuranoside (AICAR) on isoform-specific expressions of PGC-1alpha were
      investigated. All isoforms were increased in proportion to exercise intensity of
      treadmill running (10-30 m/min for 30 min). Preinjection of beta2-adrenergic
      receptor (AR) antagonist (ICI 118551) inhibited the increase in PGC-1alpha-b and
      PGC-1alpha-c mRNAs, but not the increase in PGC-1alpha-a mRNA, in response to
      high-intensity exercise. Although high-intensity exercise activated alpha2-AMP
      activated protein kinase (alpha2-AMPK) in skeletal muscles, inactivation of
      alpha2-AMPK activity did not affect high-intensity exercise-induced mRNA
      expression of all PGC-1alpha isoforms, suggesting that activation of alpha2-AMPK
      is not mandatory for an increase in PGC-1alpha mRNA by high-intensity exercise. A
      single injection in mice of AICAR, an AMPK activator, increased mRNAs of all PGC
      1alpha isoforms. AICAR increased blood catecholamine concentrations, and
      preinjection of beta2-AR antagonist inhibited the increase in PGC-1alpha-b and
      PGC-1alpha-c mRNAs but not the increase in PGC-1alpha-a mRNA. Direct exposure of
      epitrochlearis muscle to AICAR increased PGC-1alpha-a but not the -b isoform.
      These data indicate that exercise-induced PGC-1alpha expression was dependent on
      the intensity of exercise. Exercise or AICAR injection increased PGC-1alpha-b and
      PGC-1alpha-c mRNAs via beta2-AR activation, whereas high-intensity exercise
      increased PGC-1alpha-a expression by a multiple mechanism in which alpha2-AMPK is
      one of the signaling pathways.

PMID- 21098737
TI  - Organ-specific dietary fatty acid uptake in humans using positron emission
      tomography coupled to computed tomography.
AB  - A noninvasive method to determine postprandial fatty acid tissue partition may
      elucidate the link between excess dietary fat and type 2 diabetes. We
      hypothesized that the positron-emitting fatty acid analog 14(R,S)-[(18)F]fluoro-6
      thia-heptadecanoic acid ((18)FTHA) administered orally during a meal would be
      incorporated into chylomicron triglycerides, allowing determination of interorgan
      dietary fatty acid uptake. We administered (18)FTHA orally at the beginning of a
      standard liquid meal ingested in nine healthy men. There was no significant
      (18)FTHA uptake in the portal vein and the liver during the 1st hour. Whole body
      PET/CT acquisition revealed early appearance of (18)FTHA in the distal thoracic
      duct, reaching a peak at time 240 min. (18)FTHA mean standard uptake value
      increased progressively in the liver, heart, quadriceps, and subcutaneous and
      visceral adipose tissues between time 60 and 240 min. Most circulating (18)F
      activity between time 0 and 360 min was recovered into chylomicron triglycerides.
      Using Triton WR-1339 treatment in rats that received (18)FTHA by gavage, we
      confirmed that >90% of this tracer reached the circulation as triglycerides. This
      novel noninvasive method to determine tissue dietary fatty acid distribution in
      humans should prove useful in the study of the mechanisms leading to
      lipotoxicity.

PMID- 21098738
TI  - Insulin-induced serine phosphorylation of IRS-2 via ERK1/2 and mTOR: studies on
      the function of Ser675 and Ser907.
AB  - The identity of specific serine phosphorylation residues of insulin receptor
      substrate (IRS)-2 and their impact on insulin signal transduction are largely
      unknown. Ser(675) and Ser(907) of mouse IRS-2 are adjacent to PI 3-kinase or Grb2
      binding domains, respectively. Using monoclonal phosphosite-specific antibodies,
      we demonstrated the phosphorylation of both serines after stimulation of Fao
      hepatoma cells with insulin, anisomycin, or phorbol esters. Phosphorylation of
      both sites was a late and prolonged event during insulin treatment and was also
      detected in liver tissue of insulin-treated as well as refed mice. Inhibition and
      siRNA-mediated knockdown of ERK1/2 indicated that the insulin-induced
      phosphorylation of Ser(907) was ERK dependent. Phosphorylation of Ser(907) did
      not prevent the insulin-induced association of IRS-2 with Grb2, but
      phosphorylation of the adjacent Tyr(911) was proved to be crucial in HEK 293
      cells expressing IRS-2 Ala mutants. The insulin-induced phosphorylation of
      Ser(675) was prevented by inhibition and siRNA-mediated knockdown of mTOR but not
      of p70(S6K1). Mutation of Ser(675) to Ala did not affect downstream insulin
      signaling but increased the half-life of the protein, suggesting an involvement
      of phospho-Ser(675) in an accelerated degradation of IRS-2. Moreover, the insulin
      induced degradation of IRS-2 was blocked by inhibition of mTOR. We conclude that
      the two novel insulin-dependent serine phosphorylation sites of IRS-2 were not
      involved in the regulation of the adjacent PI 3-kinase and Grb2 binding domains
      but might be implicated in the ERK- and mTOR-mediated negative feedback control.

PMID- 21098739
TI  - Perceptual organization without perception. The subliminal learning of global
      contour.
AB  - A critical step in visual perceptual processing is integrating local visual
      elements into contours so that shapes can be derived from them. It is often
      assumed that contour integration may reflect hardwired coding of low-level visual
      features. In this study, we present novel evidence indicating that integration of
      local elements into contours can be learned subliminally, despite being
      irrelevant to the training task and despite the local properties of the display
      varying randomly during training. Learning occurred only when contours were
      consistently paired with task-relevant targets--echoing the findings of previous
      studies on subliminal learning of low-level features. Our data indicate that task
      irrelevant, exposure-based learning extends beyond local low-level visual
      features and may play a critical role at multiple levels of visual perceptual
      organization.

PMID- 21098740
TI  - Achievement of VGPR to induction therapy is an important prognostic factor for
      longer PFS in the IFM 2005-01 trial.
AB  - In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as
      induction therapy before autologous stem cell transplantation was superior to
      vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess
      the prognostic impact of initial characteristics as well as response to therapy
      in patients enrolled in this study. Multivariate analysis showed that ISS stages
      2 and 3 and achievement of response less than very good partial response (VGPR)
      both after induction therapy and after autologous stem cell transplantation were
      adverse prognostic factors for progression-free survival, the most important one
      being achievement of response less than VGPR after induction. Progression-free
      survival was significantly improved with bortezomib-dexamethasone induction
      therapy in patients with poor-risk cytogenetics and ISS stages 2 and 3 compared
      with vincristine-adriamycin-dexamethasone. In these 2 groups of patients,
      achievement of at least VGPR after induction was of major importance. This study
      is registered with EudraCT (https://eudract.ema.europa.eu; EUDRACT 2005-000537
      38) and http://clinicaltrials.gov (NCT00200681).

PMID- 21098741
TI  - SR-A/MARCO-mediated ligand delivery enhances intracellular TLR and NLR function,
      but ligand scavenging from cell surface limits TLR4 response to pathogens.
AB  - Phagocytic and pathogen sensing receptors are responsible for particle uptake and
      inflammation. It is unclear how these receptors' systems influence each other's
      function to shape an innate response. The class-A scavenger receptors SR-A
      (scavenger receptor A) and MARCO (macrophage receptor with collagenous structure)
      are 2 well-characterized phagocytic receptors that are unable to initiate
      inflammatory responses by themselves, yet are implicated in the pathogenesis of
      various inflammatory disorders. However, the mechanism for such an apparent
      discrepancy is still unclear. We utilized SR-A(-/-), MARCO(-/-), and SR-A(-/-)
      MARCO(-/-) mice, along with microbe-derived, environmental, and synthetic
      polyanions to assess the inflammatory responses following combinatorial ligation
      of SR-A/MARCO and selected Toll-like receptors (TLRs) and nucleotide-binding
      oligomerization domain (NOD)-like receptors (NLRs) by their shared ligands. In
      addition to ligating SR-A and MARCO, these agonists also selectively activated
      the cell-surface sensor TLR4, endosomal TLR3, and the cytosolic NOD2 and NALP3
      (NACHT domain-, leucine-rich repeat-, and pyrin domain-containing protein 3). We
      show that, following recognition of common ligands, SR-A and MARCO attenuate TLR4
      mediated responses while enhancing responses by the intracellular TLR3, NOD2, and
      NALP3. We conclude that SR-A/MARCO-mediated rapid ligand internalization
      prevented sensing by surface TLRs while increasing ligand availability in
      intracellular compartments, thus allowing sensing and robust responses by
      intracellular sensors.

PMID- 21098742
TI  - Pregnancy outcomes after maternal exposure to rituximab.
AB  - Rituximab is a chimeric anti-CD20 monoclonal B cell-depleting antibody indicated
      for certain hematologic malignancies and active rheumatoid arthritis with
      inadequate response to tumor necrosis factor antagonists. Despite counseling to
      avoid pregnancy, women may inadvertently become pregnant during or after
      rituximab treatment. Using the rituximab global drug safety database, we
      identified 231 pregnancies associated with maternal rituximab exposure. Maternal
      indications included lymphoma, autoimmune cytopenias, and other autoimmune
      diseases. Most cases were confounded by concomitant use of potentially
      teratogenic medications and severe underlying disease. Of 153 pregnancies with
      known outcomes, 90 resulted in live births. Twenty-two infants were born
      prematurely; with one neonatal death at 6 weeks. Eleven neonates had hematologic
      abnormalities; none had corresponding infections. Four neonatal infections were
      reported (fever, bronchiolitis, cytomegalovirus hepatitis, and chorioamnionitis).
      Two congenital malformations were identified: clubfoot in one twin, and cardiac
      malformation in a singleton birth. One maternal death from pre-existing
      autoimmune thrombocytopenia occurred. Although few congenital malformations or
      neonatal infections were seen among exposed neonates, women should continue to be
      counseled to avoid pregnancy for <= 12 months after rituximab exposure; however,
      inadvertent pregnancy does occasionally occur. Practitioners are encouraged to
      report complete information to regulatory authorities for all pregnancies with
      suspected or known exposure to rituximab.

PMID- 21098743
TI  - Drug-eluting or bare metal stents for the treatment of saphenous vein graft
      disease: a Bayesian meta-analysis.
AB  - BACKGROUND: Observational studies and randomized, controlled trials have yielded
      uncertain results regarding the benefits of drug-eluting stents (DES) for the
      treatment of saphenous vein graft (SVG) disease. The objective of this meta
      analysis was to assess the cumulative evidence regarding the efficacy and
      effectiveness of DES to treat SVG compared with bare metal stent (BMS). METHODS
      AND RESULTS: We conducted a bayesian hierarchical meta-analysis of all
      randomized, controlled trials and observational studies that compared clinical
      outcomes after DES or BMS placement in SVG disease. Our search resulted in 25
      studies, cumulating 5755 patients. DES implantation was not associated with an
      increased risk of death (odds ratio [OR], 0.85; 95% credible intervals (CrI)
      [CrI], 0.62 to 1.21) or myocardial infarction (OR, 0.83; 95% CrI, 0.56 to 1.32),
      but wide CrIs preclude definitive conclusions. Target vessel revascularization
      (OR, 0.55; 95% CrI, 0.39 to 0.76) and target lesion revascularization (OR, 0.58;
      95% CrI, 0.37 to 0.87) were both reduced by approximately 45% with DES. When
      combining these outcomes, the OR for major adverse cardiac events was reduced in
      patients treated with DES (OR, 0.62; 95% CrI, 0.46 to 0.81). Finally, the
      relative risk of stent thrombosis appeared lower with DES, although again the
      CrIs were very wide (OR, 0.54; 95% CrI, 0.13 to 1.39). CONCLUSIONS: In this study
      level meta-analysis, the largest ever reported and the first using bayesian
      methods, the use of DES for the treatment of SVG disease reduces target vessel
      revascularization and target lesion revascularization procedures compared with
      BMS. Although there is no evidence to date to suggest increased rates of
      mortality, myocardial infarction, or stent thrombosis, further data are needed to
      address this safety issue.

PMID- 21098744
TI  - Predictors of neurological events associated with carotid artery stenting in high
      surgical-risk patients: insights from the Cordis Carotid Stent Collaborative.
AB  - BACKGROUND: Comorbid and anatomic characteristics that portend higher procedural
      risk are well defined for carotid endarterectomy but less so for carotid artery
      stenting. METHODS AND RESULTS: We pooled carotid stent data from 4 Cordis
      sponsored trials (n=2104) with similar patient cohorts and end point
      determination to identify predictors of neurological death or stroke within 30
      days of the procedure. Median age was 74 years (24% >80 years), 36% were women,
      and 24.2% were symptomatic in the previous 6 months. There were 88 (4.2%)
      neurological deaths or strokes at 30 days. Among symptomatic patients, the risk
      of adverse neurological outcome declined with increasing time between the
      incident neurological event and carotid stent procedure. In a logistic regression
      model that included preprocedural and procedural variables, significant
      multivariable predictors of 30-day neurological death or stroke were older age
      (continuous), black race, angiographically visible thrombus in symptomatic
      patients, procedural use of glycoprotein IIb/IIIa inhibitors, procedural
      transient ischemic attack, final residual stenosis >30%, and periprocedural use
      of protamine or vasopressors. CONCLUSIONS: In this pooled analysis, a number of
      preprocedural and procedural factors predicted higher risk of stroke and
      neurological death within 30 days of a carotid stent procedure. Identification of
      such predictors may help to guide patient selection and further refine procedural
      technique.

PMID- 21098745
TI  - Magnetic resonance-guided cardiac interventions using magnetic resonance
      compatible devices: a preclinical study and first-in-man congenital
      interventions.
AB  - BACKGROUND: Percutaneous cardiac interventions are currently performed under x
      ray guidance. Magnetic resonance imaging (MRI) has been used to guide
      intravascular interventions in the past, but mainly in animals. Translation of MR
      guided interventions into humans has been limited by the lack of MR-compatible
      and safe equipment, such as MR guide wires with mechanical characteristics
      similar to standard guide wires. The aim of the present study was to evaluate the
      safety and efficacy of a newly developed MR-safe and compatible passive guide
      wire in aiding MR-guided cardiac interventions in a swine model and describe the
      2 first-in-man solely MR-guided interventions. METHODS AND RESULTS: In the
      preclinical trial, the new MR-compatible wire aided the performance of 20
      interventions in 5 swine. These consisted of balloon dilation of nondiseased
      pulmonary and aortic valves, aortic arch, and branch pulmonary arteries. After
      ethics and regulatory authority approval, the 2 first-in-man MR-guided
      interventions were performed in a child and an adult, both with elements of
      valvar pulmonary stenosis. Catheter manipulations were monitored with real-time
      MRI sequence with interactive modification of imaging plane and slice position.
      Temporal resolution was 11 to 12 frames/s. Catheterization procedure times were
      110 and 80 minutes, respectively. Both patients had successful relief of the
      valvar stenosis and no procedural complications. CONCLUSIONS: The described
      preclinical study and case reports are encouraging that with the availability of
      the new MR-compatible and safe guide wire, certain percutaneous cardiac
      interventions will become feasible to perform solely under MR guidance in the
      future. A clinical trial is underway in our institution.

PMID- 21098746
TI  - Comment: diabetes medications related to an increased risk of falls and fall
      related morbidity in the elderly.

PMID- 21098747
TI  - Comment: identifying optimal initial infusion rates for unfractionated heparin in
      morbidly obese patients.

PMID- 21098749
TI  - Subcutaneous unfractionated heparin for treatment of venous thromboembolism in
      end-stage renal disease.
AB  - OBJECTIVE: To report 3 cases of venous thromboembolism (VTE) in patients with end
      stage renal disease (ESRD) treated with subcutaneous unfractionated heparin (UFH)
      bridged with warfarin. CASE SUMMARIES: Three patients with ESRD were successfully
      treated for VTE with unmonitored, fixed-dose subcutaneous UFH every 12 hours and
      dose-adjusted warfarin. The first patient was initiated on continuous infusion
      UFH for deep-vein thrombosis, but due to poor vascular access, nurses were unable
      to consistently measure anti-Xa levels. Therefore, subcutaneous UFH 17,500 units
      (~245 units/kg/dose) every 12 hours was initiated. Oral warfarin 5 mg/day was
      started the following day. The patient received 4 days of inpatient subcutaneous
      UFH and then was discharged to complete the bridge as an outpatient. The second
      patient received subcutaneous UFH 10,000 units (~244 units/kg/dose) every 12
      hours and oral warfarin 2.5 mg/day to treat a nonocclusive thrombus along her
      right femoral vein hemodialysis catheter. The patient received 1 day of inpatient
      subcutaneous UFH treatment prior to discharge and continued bridge therapy with
      warfarin as an outpatient. The third patient was initiated on subcutaneous UFH
      20,000 units (~223 units/kg/dose) every 12 hours and oral warfarin 7.5 mg/day due
      to a subtherapeutic INR (1.50) 5 days after receiving fresh frozen plasma to
      reduce her therapeutic INR for a procedure. The patient received 2 doses of
      subcutaneous UFH as an inpatient before treatment was discontinued because her
      INR was therapeutic at 2.3. DISCUSSION: Subcutaneous UFH has been used to treat
      VTE since the early 1980s; however, with the advent of low-molecular-weight
      heparin (LMWH), subcutaneous UFH use diminished. Several studies comparing the
      use of subcutaneous UFH to both continuous infusion UFH and LMWH concluded that
      subcutaneous UFH is a safe and efficacious alternative. The 2008 Chest Guidelines
      for Antithrombotic Therapy for Venous Thromboembolic Disease support the use of
      subcutaneous UFH for the treatment of VTE with a Grade 1A recommendation and
      provide a Grade 2C recommendation for use of UFH over LMWH for patients with VTE
      and severe renal failure. CONCLUSIONS: Safe and convenient treatment options for
      VTE in patients with ESRD are limited. Fixed-dose, unmonitored subcutaneous UFH
      as a bridge to warfarin therapy is an effective option in patients with ESRD and
      those with financial restrictions. The pharmacist plays a key role in identifying
      patients for whom subcutaneous UFH treatment may be a viable alternative,
      recommending an appropriate dosing regimen, and educating health-care
      professionals and patients about safe use.

PMID- 21098750
TI  - First report of lamotrigine-induced drug rash with eosinophilia and systemic
      symptoms syndrome with pancreatitis.
AB  - OBJECTIVE: To report a case of lamotrigine-induced drug rash with eosinophilia
      and systemic symptoms (DRESS) syndrome with pancreatitis as the initial visceral
      involvement. CASE SUMMARY: A 75-year-old man was admitted to the local hospital
      for generalized tonic-clonic seizures. Results of the clinical examination and
      neurologic investigations were unremarkable. Lamotrigine treatment was initiated
      and the patient was discharged a few days later. Forty days after lamotrigine
      initiation, he developed an exanthematous maculopapular rash with fever,
      peripheral lymphadenopathies, and hypereosinophilia. Lamotrigine hypersensitivity
      was suspected and the drug was suspended on day 45. On day 47, the patient
      presented with acute abdominal pain with an elevated lipase level. Acute
      pancreatitis was confirmed on computed tomography scan. The patient's condition
      worsened and he was transferred to the intensive care unit with multiorgan
      failure. The diagnosis of lamotrigine-induced DRESS syndrome was confirmed by a
      compatible skin histology and concomitant human herpesvirus-6 infection.
      DISCUSSION: This observation has 2 points of interest. First, pancreatic toxicity
      of lamotrigine has been rarely reported in the literature. Secondly, pancreatitis
      is uncommon at the early stage of DRESS syndrome. Only 1 other case of DRESS
      syndrome, secondary to allopurinol, reports pancreatitis along with an Epstein
      Barr virus infection. The Naranjo probability scale indicated a probable
      causality between lamotrigine and DRESS syndrome in this patient. CONCLUSIONS:
      This is the first reported case of lamotrigine-induced DRESS syndrome with
      pancreatitis as the initial visceral involvement. Clinicians should be aware of
      this mode of presentation of DRESS syndrome.

PMID- 21098752
TI  - Phenobarbital/Lamotrigine coadministration-induced blood dyscrasia in a patient
      with epilepsy.
AB  - OBJECTIVE: To report on a patient with epilepsy who developed leukopenia and
      thrombocytopenia during phenobarbital/lamotrigine treatment. CASE REPORT: A 45
      year-old woman with a 10-year history of complex partial seizures being treated
      with phenobarbital 100 mg/day presented due to the development of complex partial
      seizure episodes (8 episodes/month in the last 6 months). Results of laboratory
      tests on admission showed normal platelets (250 x 103/MUL) and white blood cells
      (8.2 x 103/MUL). After clinical evaluation, lamotrigine titrated to a final dose
      of 100 mg twice daily was added to the phenobarbital. About 2 months later no
      epileptic manifestations were reported, but hematologic tests revealed a decrease
      in both platelets (36 x 103/MUL) and white blood cells (2.0 x 103/MUL). One day
      later, phenobarbital was discontinued and the patient developed 2 episodes of
      complex partial seizure. Levetiracetam titrated to 1500 mg/day was added to
      lamotrigine, with a normalization of platelets (260 x 103/MUL) and white blood
      cell (7.9 x 103/MUL) counts about 20 days later. After a few days, levetiracetam
      was discontinued and phenobarbital rechallenge during lamotrigine treatment
      induced a new blood dyscrasia in about 2 weeks (platelets 80 x 103/MUL; white
      blood cells 3.2 x 103/MUL). Phenobarbital was discontinued and levetiracetam was
      restarted, with a recovery of normal hematopoiesis in 25 days. The patient is
      presently receiving treatment with both lamotrigine 200 mg/day and levetiracetam
      1500 mg/day and shows no seizure symptoms, blood abnormalities, or other adverse
      effects. DISCUSSION: Using the Horn Drug Interaction Probability Scale, we
      estimated a probable relationship between the drug-drug interaction and blood
      dyscrasia. The underlying mechanism of this interaction has not been well
      characterized. Cytochrome P450 enzyme induction by phenobarbital could be
      responsible for the production of reactive metabolites of lamotrigine that might
      be causative for the observed hematologic effects. A pharmacodynamic interaction
      between the 2 drugs is also a possible mechanism of this interaction.
      CONCLUSIONS: Our patient with epilepsy developed blood dyscrasia during
      lamotrigine/phenobarbital treatment. Clinicians should carefully monitor
      hematologic parameters during lamotrigine/phenobarbital treatment.

PMID- 21098753
TI  - Medication reconciliation during internal hospital transfer and impact of
      computerized prescriber order entry.
AB  - BACKGROUND: Internal hospital transfer is a vulnerable time during which patients
      are at high risk of medication discrepancies that can result in clinically
      significant harm, medication errors, and adverse drug events. OBJECTIVE: To
      identify, characterize, and assess the clinical impact of unintentional
      medication discrepancies during internal hospital transfer and to investigate the
      influence of computerized prescriber order entry (CPOE) on medication
      discrepancies. METHODS: All patients transferred between 10 inpatient units at 2
      tertiary care hospitals were prospectively assessed to identify discrepancies.
      Interfaces included transfers between (1) units that both used paper-based
      medication ordering systems; (2) units that both used CPOE-based systems; and (3)
      units that used both paper-based and CPOE-based systems (hybrid transfer). The
      primary endpoint was the number of patients with at least 1 unintentional
      medication discrepancy during internal hospital transfer. Discrepancies were
      identified through assessment and comparison of a best possible medication
      transfer list with the actual transfer orders. A multidisciplinary team of
      clinicians assessed the potential clinical impact and severity of unintentional
      discrepancies. RESULTS: Overall, 190 patients were screened and 129 patients were
      included. Eighty patients (62.0%) had at least 1 unintentional medication
      discrepancy at the time of transfer, and the most common discrepancy was
      medication omission (55.6%). Factors that independently increased the risk of a
      patient experiencing at least 1 unintentional discrepancy included lack of best
      possible medication history, increasing number of home medications, and
      increasing number of transfer medications. Forty-seven patients (36.4%) had at
      least 1 unintentional discrepancy with the potential to cause discomfort and/or
      clinical deterioration. The risk of discrepancies was present regardless of the
      medication-ordering system (paper, CPOE, or hybrid). CONCLUSIONS: Clinically
      significant medication discrepancies occur commonly during internal hospital
      transfer. A structured, collaborative, and clearly defined medication
      reconciliation process is needed to prevent internal transfer discrepancies and
      patient harm.

PMID- 21098754
TI  - Pharmacologic management of heart failure with preserved ejection fraction.
AB  - OBJECTIVE: To provide an overview of heart failure with preserved ejection
      fraction (HFPEF), as well as its pathophysiology, diagnosis, and clinical
      evidence regarding its pharmacologic management. DATA SOURCES: Peer-reviewed
      articles were identified from MEDLINE, International Pharmaceutical Abstracts,
      and Current Contents (all 1966-August 2010) using the search terms heart failure
      with preserved ejection fraction, diastolic dysfunction, diastolic heart failure,
      angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers
      (ARBs), digoxin, beta-blockers, calcium-channel blockers, and vasodilators.
      Citations from available articles were also reviewed for additional references.
      STUDY SELECTION AND DATA EXTRACTION: Fourteen published manuscripts relating to
      pharmacologic management of HFPEF were identified. DATA SYNTHESIS: The prevalence
      of HFPEF has continued to increase. Compared to heart failure with left
      ventricular systolic dysfunction, HFPEF has been largely understudied. Unlike in
      the management of heart failure with left ventricular systolic dysfunction, ACE
      inhibitors, ARBs, beta-blockers, and aldosterone antagonists did not demonstrate
      mortality benefit in HFPEF, with the exception of one small study evaluating the
      use of propranolol. However, this study enrolled a small number of patients with
      recent history of myocardial infarction, which limited the generalizability of
      the results. Most of the current evidence centers on morbidity benefits and
      symptom reduction. One study showed that treatment with candesartan reduced
      hospital admissions in this population of patients. Management of HFPEF still
      focuses on optimally managing underlying diseases (eg, hypertension).
      CONCLUSIONS: Much remains to be learned about the appropriate pharmacologic
      management of patients with HFPEF. Hypertension is in most cases the predominant
      contributor to its development and progression. For this reason, antihypertensive
      treatment, including ACE inhibitors, ARBs, beta-blockers, and calcium-channel
      blockers, has been evaluated and is recommended to control the disease in this
      patient population, although these agents have not demonstrated significant
      benefit beyond blood pressure control. Further research into the pathophysiology
      of HFPEF may contribute to identifying the most optimal agent in managing this
      disease.

PMID- 21098755
TI  - Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis in
      patients without gastrointestinal bleeding.
AB  - OBJECTIVE: To review relevant studies for both primary and secondary antibiotic
      prophylaxis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis
      without gastrointestinal bleeding. DATA SOURCES: A search of PubMed (1980-July
      2010) was conducted using the terms prophylaxis, SBP, and antibiotics. A manual
      review of bibliographies was conducted for inclusion of relevant articles. STUDY
      SELECTION AND DATA EXTRACTION: Prospective studies and meta-analyses published in
      English were included. DATA SYNTHESIS: Ten trials and 3 meta-analyses were
      included. Of the 10 trials, 2 examined the use of secondary prophylaxis for
      prevention of subsequent episodes of SBP, 4 examined the use of primary
      prophylaxis to prevent an initial SBP episode, and 4 examined the use of
      antibiotic prophylaxis in a mixed population. Seven trials evaluated the use of
      an antibiotic compared to placebo or no treatment. Only 1 trial evaluated
      norfloxacin versus trimethoprim/sulfamethoxazole. Trial duration varied from 24
      days to 12 months. In general, trials examining norfloxacin as secondary
      prophylaxis found significantly decreased occurrence of SBP but no significant
      difference in mortality rates. Primary prophylaxis studies found no significant
      difference in the incidence of infections, including SBP, with norfloxacin or
      ciprofloxacin treatment but significantly lower incidence of gram-negative
      infections. Mixed population studies found a significantly decreased incidence of
      SBP but no significant difference in mortality. In the 3 meta-analyses, a
      significant decrease in mortality and an overall decrease in SBP incidence in the
      treatment groups were noted. CONCLUSIONS: Based on currently available data, the
      use of prophylactic antibiotic therapy is warranted for the prevention of
      recurrent SBP in patients with cirrhosis and ascites. In patients with low
      ascetic fluid protein and at least 1 more risk factor, primary prophylaxis may be
      considered. Further studies with improved methodology are needed to determine
      whether prophylactic antibiotic therapy has an impact on mortality.

PMID- 21098756
TI  - Plerixafor dosing and administration in a patient with dialysis-dependent renal
      failure.
AB  - OBJECTIVE: To report on the use of plerixafor in a patient with multiple myeloma
      and dialysis-dependent renal failure. CASE SUMMARY: A 38-year-old man with
      multiple myeloma and dialysis-dependent renal failure was evaluated for stem cell
      transplantation. Stem cell mobilization with 6 doses of granulocyte colony
      stimulating factor (G-CSF) 10 MUg/kg/day yielded an inadequate maximum pre
      apheresis CD34+ count of 5.6 cells/MUL. The patient was treated with a
      postdialysis subcutaneous dose of plerixafor 160 MUg/kg after 4 days of G-CSF
      therapy. After a single dose of plerixafor, the patient's pre-apheresis CD34+
      count was 125.6 cells/MUL. After 1 apheresis session, the stem cell collection
      yield was 5.33 x 106 CD34+ cells/kg. There were no observed plerixafor
      toxicities. The patient underwent successful autologous stem cell
      transplantation. Times to neutrophil and platelet engraftment were 12 and 15
      days, respectively. At 100-day follow-up, the patient's myeloma was in remission
      and he met all criteria for durable engraftment. DISCUSSION: Renal impairment is
      a common comorbidity in patients with multiple myeloma. Plerixafor is a chemokine
      receptor 4 antagonist approved for use to mobilize stem cells for collection and
      subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and
      multiple myeloma. To date, there is limited information on safe and effective
      dosing and administration of plerixafor in patients who are dialysis-dependent.
      This report describes the use of plerixafor in a patient with multiple myeloma
      and dialysis-dependent renal failure. CONCLUSIONS: Based on our experience, we
      are instituting a policy to administer plerixafor at Food and Drug Administration
      approved renal adjustment doses in patients on hemodialysis, with dialysis
      sessions scheduled prior to plerixafor administration and repeated as necessary
      after apheresis and prior to subsequent plerixafor doses. If clinically feasible,
      dialysis should be held during the days required to collect stem cells.

PMID- 21098757
TI  - Analysis of pharmaceutical safety-related regulatory actions in Japan: do
      tradeoffs exist between safer drugs and launch delay?
AB  - BACKGROUND: Prediction and management of drug safety is a global regulatory
      issue. Safety-related regulatory actions (SRRAs) are taken mostly when unexpected
      adverse drug reactions occur. Currently, Japan is reconciled to delayed access to
      new drugs (ie, launch delay compared to Western countries), but may have been
      benefiting by free-riding on safety data accumulated in other countries prior to
      Japanese launch. OBJECTIVE: To identify factors that are significantly associated
      with SRRAs, and to discuss the challenges that Japan might have to face with
      increasing access to new drugs. METHODS: The SRRAs of 135 new drugs approved from
      January 2000 to December 2005 were analyzed to investigate association with
      launch lag, company and drug characteristics, market size, submission data, and
      regulatory status. SRRAs were measured in terms of the number of emergency safety
      information notifications and official safety instructions issued by the Japanese
      regulatory agency within 3 years after approval. A negative binomial distribution
      model was used for regression analysis. RESULTS: Longer launch lags and presence
      of drugs with similar modes of action were associated with fewer SRRAs. Bridging
      strategy showed increased SRRAs. No significant association was observed between
      SRRAs and the subject number in clinical data packages. Occurrence of SRRAs was
      varied among development strategy, preceding products, and regional regulations.
      CONCLUSIONS: The occurrence of SRRAs was associated with the accumulation of both
      foreign and domestic postmarketing evidence rather than with clinical trial data
      upon launch. Considering the paradigm shift to simultaneous global drug
      development and filing for regulatory approval, this study indicates the
      importance of intensive data collection in the early postmarketing phase and use
      of safety information in early markets. However, even if we would be sufficiently
      cautious about safety risks of new drugs, a population that enjoys first-in-class
      drugs probably has to bear the risks.

PMID- 21098759
TI  - Family history of cancer and cancer risks in women with BRCA1 or BRCA2 mutations.
AB  - Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks
      of breast and ovarian cancers. However, the influence of a family history of
      these cancers on these risks in women with BRCA mutations is unclear. We
      calculated cancer incidence rates for a multinational cohort comprising 3011
      women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years,
      during which time 243 incident breast or ovarian cancers were recorded. The 10
      year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] =
      13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to
      21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the
      risk of breast cancer increased by 1.2-fold for each first-degree relative with
      breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence
      interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6
      fold for each first- or second-degree relative with ovarian cancer (HR = 1.61;
      95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast
      cancer increased by 1.7-fold for each first-degree relative younger than 50 years
      with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07).

PMID- 21098760
TI  - Meta-analysis: should it be more than the sum of its parts?

PMID- 21098758
TI  - Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy
      in a population-based cohort.
AB  - BACKGROUND: Cofactors might affect the risk of the rare progression from
      infection with carcinogenic human papillomavirus (HPV) to cervical premalignancy
      to invasive cancer. Some studies have observed that Chlamydia trachomatis
      infection is associated with increased risk for cervical cancer. In a large
      prospective cohort, we assessed the role of C trachomatis in cervical
      premalignancy and addressed confounding by HPV. METHODS: We identified 182 women
      with prevalent and 132 women with incident histological cervical intraepithelial
      neoplasia grade 2 (CIN2), grade 3 (CIN3), or cervical cancer (CIN2+) in the Costa
      Rica HPV Natural History Study. Control subjects were 995 (approximately 10% of
      the 10 049) subjects who were randomly selected from the same study. Cervical HPV
      status at enrollment was determined by MY09/MY11 polymerase chain reaction
      amplification and dot-blot hybridization. The presence of C trachomatis DNA in
      cervical exfoliated cells at enrollment was determined by a novel serovar
      specific polymerase chain reaction-based C trachomatis detection and genotyping
      assay. Plasma drawn at enrollment from each subject was used to determine C
      trachomatis immunoglobulin G (IgG) status. Logistic regression was used to
      examine the association between C trachomatis and CIN2+, taking into account
      possible confounding by HPV. RESULTS: C trachomatis positivity at enrollment was
      associated with CIN2+ and concurrent and subsequent carcinogenic HPV infection.
      To account for confounding by HPV status, we restricted the analysis to women
      positive for carcinogenic HPV DNA at enrollment and found no association between
      C trachomatis status (as assessed by DNA or IgG) at enrollment and combined
      prevalent and/or incident CIN2+ (for C trachomatis DNA positivity, odds ratio =
      0.77, 95% confidence interval = 0.42 to 1.41; for C trachomatis seropositivity,
      odds ratio = 1.09, 95% confidence interval = 0.85 to 1.41). CONCLUSIONS: We found
      no association between C trachomatis status, as assessed by DNA or IgG, and risk
      of cervical premalignancy, after controlling for carcinogenic HPV-positive
      status. Previous positive associations between C trachomatis and cervical
      premalignancy could have been caused, in part, by an increased susceptibility to
      HPV infection.

PMID- 21098761
TI  - Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Dose-dense chemotherapy has become a mainstay regimen in the adjuvant
      setting for women with high-risk breast cancer. We performed a systematic review
      and meta-analysis of the existing data from randomized controlled trials
      regarding the efficacy and toxicity of the dose-dense chemotherapy approach in
      nonmetastatic breast cancer. METHODS: Randomized controlled trials that compared
      a dose-dense chemotherapy protocol with a standard chemotherapy schedule in the
      neoadjuvant or adjuvant setting in adult women older than 18 years with breast
      cancer were identified by searching The Cochrane Cancer Network register of
      trials, The Cochrane Library, and LILACS and MEDLINE databases (from January 1966
      to January 2010). Hazard ratios (HRs) of death and recurrence and relative risks
      of adverse events were estimated and pooled. All statistical tests were two
      sided. RESULTS: Ten trials met the inclusion criteria and were classified into
      two categories based on trial methodology. Three trials enrolling 3337 patients
      compared dose-dense chemotherapy with a conventional chemotherapy schedule
      (similar agents). Patients who received dose-dense chemotherapy had better
      overall survival (HR of death = 0.84, 95% confidence interval [CI] = 0.72 to
      0.98, P = .03) and better disease-free survival (HR of recurrence or death =
      0.83, 95% CI = 0.73 to 0.94, P = .005) than those on the conventional schedule.
      No benefit was observed in patients with hormone receptor-positive tumors. Seven
      trials enrolling 8652 patients compared dose-dense chemotherapy with regimens
      that use standard intervals but with different agents and/or dosages in the
      treatment arms. Similar results were obtained for these trials with respect to
      overall survival (HR of death = 0.85, 95% CI = 0.75 to 0.96, P = .01) and disease
      free survival (HR of recurrence or death = 0.81, 95% CI = 0.73 to 0.88, P <
      .001). The rate of nonhematological adverse events was higher in the dose-dense
      chemotherapy arms than in the conventional chemotherapy arms. CONCLUSION: Dose
      dense chemotherapy results in better overall and disease-free survival,
      particularly in women with hormone receptor-negative breast cancer. However,
      additional data from randomized controlled trials are needed before dose-dense
      chemotherapy can be considered as the standard of care.

PMID- 21098762
TI  - The cover. Boy drinking.

PMID- 21098763
TI  - A piece of my mind. A modern family.

PMID- 21098764
TI  - US government kicks off program for comparative effectiveness research.

PMID- 21098765
TI  - Elective intra-aortic balloon pump placement in high-risk percutaneous coronary
      intervention.

PMID- 21098766
TI  - Elective intra-aortic balloon pump placement in high-risk percutaneous coronary
      intervention.

PMID- 21098767
TI  - Elective intra-aortic balloon pump placement in high-risk percutaneous coronary
      intervention.

PMID- 21098768
TI  - Risk of birth defects after use of acyclovir, valacyclovir, and famciclovir in
      the first trimester.

PMID- 21098769
TI  - Multidisciplinary approaches to biomedical research.

PMID- 21098770
TI  - Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a
      randomized trial.
AB  - CONTEXT: Mediastinal nodal staging is recommended for patients with resectable
      non-small cell lung cancer (NSCLC). Surgical staging has limitations, which
      results in the performance of unnecessary thoracotomies. Current guidelines
      acknowledge minimally invasive endosonography followed by surgical staging (if no
      nodal metastases are found by endosonography) as an alternative to immediate
      surgical staging. OBJECTIVE: To compare the 2 recommended lung cancer staging
      strategies. DESIGN, SETTING, AND PATIENTS: Randomized controlled multicenter
      trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April
      2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal
      staging was indicated based on computed or positron emission tomography.
      INTERVENTION: Either surgical staging or endosonography (combined transesophageal
      and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical
      staging in case no nodal metastases were found at endosonography. Thoracotomy
      with lymph node dissection was performed when there was no evidence of
      mediastinal tumor spread. MAIN OUTCOME MEASURES: The primary outcome was
      sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was
      surgical pathological staging. Secondary outcomes were rates of unnecessary
      thoracotomy and complications. RESULTS: Two hundred forty-one patients were
      randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also
      underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95%
      confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95%
      CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%
      59%) by endosonography followed by surgical staging (P = .02). This corresponded
      to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%)
      (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary
      in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95%
      CI, 4%-13%) in the endosonography group (P = .02). The complication rate was
      similar in both groups. CONCLUSIONS: Among patients with (suspected) NSCLC, a
      staging strategy combining endosonography and surgical staging compared with
      surgical staging alone resulted in greater sensitivity for mediastinal nodal
      metastases and fewer unnecessary thoracotomies. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00432640.

PMID- 21098771
TI  - Effects of aerobic and resistance training on hemoglobin A1c levels in patients
      with type 2 diabetes: a randomized controlled trial.
AB  - CONTEXT: Exercise guidelines for individuals with diabetes include both aerobic
      and resistance training although few studies have directly examined this exercise
      combination. OBJECTIVE: To examine the benefits of aerobic training alone,
      resistance training alone, and a combination of both on hemoglobin A(1c)
      (HbA(1c)) in individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS:
      A randomized controlled trial in which 262 sedentary men and women in Louisiana
      with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9
      month exercise program between April 2007 and August 2009. INTERVENTION: Forty
      one participants were assigned to the nonexercise control group, 73 to resistance
      training 3 days a week, 72 to aerobic exercise in which they expended 12 kcal/kg
      per week; and 76 to combined aerobic and resistance training in which they
      expended 10 kcal/kg per week and engaged in resistance training twice a week.
      Main Outcome Change in HbA(1c) level. Secondary outcomes included measures of
      anthropometry and fitness. RESULTS: The study included 63.0% women and 47.3%
      nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a
      baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the
      absolute mean change in HbA(1c) in the combination training exercise group was 
      0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes
      in HbA(1c) were not statistically significant in either the resistance training (
      0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic (-0.24%; 95% CI, -0.55%
      to 0.07%; P = .14) groups compared with the control group. Only the combination
      exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95%
      CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups
      reduced waist circumference from -1.9 to -2.8 cm compared with the control group.
      The resistance training group lost a mean of -1.4 kg fat mass (95% CI, -2.0 to 
      0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3 to -1.1
      kg; P < .05) compared with the control group. CONCLUSIONS: Among patients with
      type 2 diabetes mellitus, a combination of aerobic and resistance training
      compared with the nonexercise control group improved HbA(1c) levels. This was not
      achieved by aerobic or resistance training alone. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00458133.

PMID- 21098772
TI  - How to use an article about quality improvement.
AB  - Quality improvement (QI) attempts to change clinician behavior and, through those
      changes, lead to improved patient outcomes. The methodological quality of studies
      evaluating the effectiveness of QI interventions is frequently low. Clinicians
      and others evaluating QI studies should be aware of the risk of bias, should
      consider whether the investigators measured appropriate outcomes, should be
      concerned if there has been no replication of the findings, and should consider
      the likelihood of success of the QI intervention in their practice setting and
      the costs and possibility of unintended effects of its implementation. This
      article complements and enhances existing Users' Guides that address the effects
      of interventions--Therapy, Harm, Clinical Decision Support Systems, and
      Summarizing the Evidence guides--with an emphasis on issues specific to QI
      studies. Given the potential for widespread implementation of QI interventions,
      there is a need for robust study methods in QI research.

PMID- 21098773
TI  - The evolution of population science: advent of the mega cohort.

PMID- 21098774
TI  - Enhancing the feasibility of large cohort studies.

PMID- 21098775
TI  - Academic medical centers' conflict of interest policies.

PMID- 21098776
TI  - Staging strategies for lung cancer.

PMID- 21098777
TI  - Combined aerobic and resistance exercise for patients with type 2 diabetes.

PMID- 21098778
TI  - JAMA patient page. Gout.

PMID- 21098779
TI  - Risk-adjusted percent time in therapeutic range as a quality indicator for
      outpatient oral anticoagulation: results of the Veterans Affairs Study to Improve
      Anticoagulation (VARIA).
AB  - BACKGROUND: Oral anticoagulation is safer and more effective when patients
      receive high-quality care. However, there have been no prior efforts to measure
      quality of oral anticoagulation care or to risk adjust it to ensure credible
      comparisons. Our objective was to profile site performance in the Veterans Health
      Administration (VA) using risk-adjusted percent time in therapeutic range (TTR).
      METHODS AND RESULTS: We included 124 551 patients who received outpatient oral
      anticoagulation from 100 VA sites of care for indications other than valvular
      heart disease from October 1, 2006, to September 30, 2008. We calculated TTR for
      each patient and mean TTR for each site of care. Expected TTR was calculated for
      each patient and each site based on the variables in the risk adjustment model,
      which included demographics, comorbid conditions, medications, and
      hospitalizations. Mean TTR for the entire sample was 58%. Site-observed TTR
      varied from 38% to 69% or from poor to excellent. Site-expected TTR varied from
      54% to 62%. Site risk-adjusted performance ranged from 18% below expected to 12%
      above expected. Risk adjustment did not alter performance rankings for many
      sites, but for other sites, it made an important difference. For example, the
      site ranked 27th of 100 before risk adjustment was one of the best (risk-adjusted
      rank, 7). Risk-adjusted site rankings were consistent from year to year
      (correlation between years, 0.89). CONCLUSIONS: Risk-adjusted TTR can be used to
      profile the quality of outpatient oral anticoagulation in a large, integrated
      health system. This measure can serve as the basis for quality measurement and
      quality improvement efforts.

PMID- 21098781
TI  - Long-term cardiovascular and noncardiovascular mortality of 1023 patients with
      confirmed acute pulmonary embolism.
AB  - BACKGROUND: There are currently no guidelines advising long-term surveillance of
      patients following an acute pulmonary embolism (PE), because long-term outcome
      studies are rare. We investigated the long-term cardiovascular and all-cause
      mortality of a large patient cohort with confirmed PE in relation to baseline
      cardiovascular disease (CVD). METHODS AND RESULTS: Clinical details of all
      patients presenting with acute PE to a tertiary hospital were retrieved from
      medical records, and their survival tracked from a statewide death registry.
      There were 1023 (45% males) patients admitted with confirmed PE from 2000 to
      2007. During a mean follow-up of 3.8+/-2.6 years, 363 patients died (35.5%), of
      whom only 31 (3.0%) died in-hospital during the index PE admission. The 3-month,
      6-month, 1-year, 3-year, and 5-year cumulative mortality rates were 8.3%, 11.1%,
      16.3%, 26.7%, and 31.6% respectively. Annual mortality did not improve over the 7
      year period. The postdischarge mortality of 8.5%/patient-year was 2.5-fold that
      of an age- and sex-matched general population, being 12.6-fold in the youngest
      quintile (<55 years) and 1.9-fold in the oldest quintile (>=83 years). Patients
      with known CVD at baseline had 2.2-fold greater all-cause mortality than those
      without CVD, and this effect, although at a lower level of risk, remained
      significant after multivariate analysis. Of the 332 deaths occurring
      postdischarge, 40% were attributed to cardiovascular causes. CONCLUSIONS: In a
      contemporary adult population, PE is associated with a substantially increased
      long-term mortality, of which nearly half is cardiovascular. Our study highlights
      the urgent need to develop long-term surveillance strategies in this population.

PMID- 21098780
TI  - Use of antithrombotic medications among elderly ischemic stroke patients.
AB  - BACKGROUND: The use of antithrombotic medications after ischemic stroke is
      recommended for deep vein thrombosis prophylaxis and secondary stroke prevention.
      We assessed the rate of receipt of these therapies among eligible ischemic stroke
      patients age >=65 years and determined the effects of age and other patient
      characteristics on treatment. METHODS AND RESULTS: The analysis included Medicare
      fee-for-service beneficiaries discharged with ischemic stroke (ICD 433.x1,
      434.x1, 436) randomly selected for inclusion in the Medicare Health Care Quality
      Improvement Program's National Stroke Project 1998 to 1999, 2000 to 2001.
      Patients discharged from nonacute facilities, transferred, or terminally ill were
      excluded. Receipt of in-hospital pharmacological deep vein thrombosis
      prophylaxis, antiplatelet medication, anticoagulants for atrial fibrillation, and
      antithrombotic medications at discharge were assessed in eligible patients,
      stratified by age (65 to 74, 75 to 84, and 85+ years). Descriptive models
      identified characteristics associated with treatment. Among 31 554 patients,
      14.9% of those eligible received pharmacological deep vein thrombosis
      prophylaxis, 83.9% antiplatelet drugs, 82.8% anticoagulants for atrial
      fibrillation, and 74.2% were discharged on an antithrombotic medication. Rates of
      treatment decreased with age and were lowest for patients ages 85 years or older.
      Admission from a skilled nursing facility and functional dependence were
      associated with lower treatment rates. CONCLUSIONS: There was substantial
      underutilization of antithrombotic therapies among elderly ischemic stroke
      patients, particularly among the very elderly, those admitted from skilled
      nursing facilities, and patients with functional dependence. The reasons for low
      use of antithrombotic therapies, including the apparent underutilization of deep
      vein thrombosis prophylaxis in otherwise eligible patients, require further
      investigation.

PMID- 21098782
TI  - Identifying important risk factors for survival in patient with systolic heart
      failure using random survival forests.
AB  - BACKGROUND: Heart failure survival models typically are constructed using Cox
      proportional hazards regression. Regression modeling suffers from a number of
      limitations, including bias introduced by commonly used variable selection
      methods. We illustrate the value of an intuitive, robust approach to variable
      selection, random survival forests (RSF), in a large clinical cohort. RSF are a
      potentially powerful extensions of classification and regression trees, with
      lower variance and bias. METHODS AND RESULTS: We studied 2231 adult patients with
      systolic heart failure who underwent cardiopulmonary stress testing. During a
      mean follow-up of 5 years, 742 patients died. Thirty-nine demographic, cardiac
      and noncardiac comorbidity, and stress testing variables were analyzed as
      potential predictors of all-cause mortality. An RSF of 2000 trees was
      constructed, with each tree constructed on a bootstrap sample from the original
      cohort. The most predictive variables were defined as those near the tree trunks
      (averaged over the forest). The RSF identified peak oxygen consumption, serum
      urea nitrogen, and treadmill exercise time as the 3 most important predictors of
      survival. The RSF predicted survival similarly to a conventional Cox proportional
      hazards model (out-of-bag C-index of 0.705 for RSF versus 0.698 for Cox
      proportional hazards model). CONCLUSIONS: An RSF model in a cohort of patients
      with heart failure performed as well as a traditional Cox proportional hazard
      model and may serve as a more intuitive approach for clinicians to identify
      important risk factors for all-cause mortality.

PMID- 21098783
TI  - Assessment of left ventricular function in older Medicare beneficiaries with
      newly diagnosed heart failure.
AB  - BACKGROUND: Assessment of left ventricular function is a recommended performance
      measure for the care of patients with newly diagnosed heart failure. Little is
      known about the extent to which left ventricular function is assessed in real
      world settings. METHODS AND RESULTS: We analyzed a 5% national sample of data
      from the Centers for Medicare and Medicaid Services from 1991 through 2008.
      Patients were 65 years or older, with incident heart failure in 1995, 1999, 2003,
      or 2007. We searched for evidence of tests of left ventricular function from 30
      days before through 60 days after an incident heart failure diagnosis. We used
      logistic regression to identify patient characteristics associated with
      assessment of left ventricular function. There were 45 005 patients with incident
      heart failure in 1995, 38 425 in 1999, 39 529 in 2003, and 32 629 in 2007.
      Assessment of left ventricular function increased from 46% to 60%, with rest
      echocardiography being the predominant mode. Patients diagnosed with heart
      failure during a hospitalization had the highest assessment rates (58% in 1995,
      64% in 1999, 69% in 2003, and 73% in 2007). After adjustment for other patient
      characteristics, odds of assessment were 4 times higher among patients diagnosed
      in inpatient settings. CONCLUSIONS: Nearly 40% of Medicare beneficiaries do not
      undergo assessment of left ventricular function when newly diagnosed with heart
      failure. Quality-improvement strategies are needed to optimize the care of these
      patients, especially in outpatient settings.

PMID- 21098784
TI  - Professional groups respond.

PMID- 21098785
TI  - Patient release issue reopened.

PMID- 21098786
TI  - SNM general and hybrid imaging guidelines.

PMID- 21098787
TI  - Alexander Gottschalk, MD.

PMID- 21098788
TI  - Kassis receives Loevinger-Berman award.

PMID- 21098789
TI  - CGMP for PET drugs: important steps to take now.

PMID- 21098792
TI  - The SNM practice guideline on breast scintigraphy.

PMID- 21098793
TI  - The SNM practice guideline on hepatobiliary scintigraphy.

PMID- 21098794
TI  - Evaluation of metabolic characteristics and viability of lipiodolized
      hepatocellular carcinomas using 18F-FDG PET/CT.
AB  - This study aimed to evaluate the metabolic characteristics of lipiodolized
      hepatocellular carcinomas (HCCs) and the diagnostic accuracy of (18)F-FDG PET/CT
      in assessing the viability of lipiodolized HCCs. METHODS: Thirty-six patients
      (age range, 32-73 y) with 38 lipiodolized HCCs who had undergone transcatheter
      arterial chemoembolization (TACE) with lipiodol before (18)F-FDG PET/CT (2-434 d)
      and 55 patients (age range, 36-77 y) with 57 treatment-naive HCCs who had not
      been treated with TACE were retrospectively studied. All patients underwent
      hepatic lobectomy or transplantation within 1 mo after PET/CT and multiphasic
      contrast-enhanced CT. (18)F-FDG uptake by lipiodolized and naive HCCs was
      compared and correlated with tumor size, pathologic grade, serum alpha
      fetoprotein (AFP) concentration, and time interval between TACE and PET/CT. The
      diagnostic accuracy of PET/CT and contrast-enhanced CT in evaluating the
      viability of lipiodolized HCC was compared. RESULTS: Histologic examination
      showed 30 viable and 8 nonviable lipiodolized HCCs. Of the 30 viable tumors, 19
      showed increased, 10 similar, and 1 decreased (18)F-FDG uptake. Of the 8
      nonviable HCCs, 3 showed increased and 5 decreased (18)F-FDG uptake. Uptake by
      viable lipiodolized HCCs was correlated with tumor size (P < 0.05) but not
      correlated with pathologic grade, AFP concentration, or interval between TACE and
      PET/CT. In contrast, (18)F-FDG uptake by naive HCCs was significantly correlated
      with tumor size and pathologic grade (P < 0.05 for each comparison). When
      lipiodolized HCCs with (18)F-FDG uptake that was greater than or similar to that
      in the surrounding normal liver were considered viable, the diagnostic
      sensitivity of PET/CT and contrast-enhanced CT in the early postembolic period
      (<3 mo) was 100% and 94%, respectively, and that in the late postembolic period
      was 93% and 79%, respectively. The specificity of (18)F-FDG PET/CT and contrast
      enhanced CT was 63% and 100%, respectively, in the acute period. Three viable
      lipiodolized HCCs with high AFP concentration were true-positives on PET/CT but
      false-negatives on contrast-enhanced CT images. CONCLUSION: After TACE, (18)F-FDG
      uptake in lipiodolized HCCs was not correlated with pathologic grade, in contrast
      to uptake in treatment-naive HCCs. (18)F-FDG PET/CT showed a high diagnostic
      sensitivity in assessing the viability of lipiodolized HCCs, with moderate
      specificity. This method may be useful in determining the viability of
      lipiodolized HCCs in patients with increased serum AFP concentration or normal
      results on contrast-enhanced CT images.

PMID- 21098795
TI  - Predicting hematologic toxicity in patients undergoing radioimmunotherapy with
      90Y-ibritumomab tiuxetan or 131I-tositumomab.
AB  - This study aimed at identifying clinical factors for predicting hematologic
      toxicity after radioimmunotherapy with (90)Y-ibritumomab tiuxetan or (131)I
      tositumomab in clinical practice. METHODS: Hematologic data were available from
      14 non-Hodgkin lymphoma patients treated with (90)Y-ibritumomab tiuxetan and 18
      who received (131)I-tositumomab. The percentage baseline at nadir and 4 wk post
      nadir and the time to nadir were selected as the toxicity indicators for both
      platelets and neutrophils. Multiple linear regression analysis was performed to
      identify significant predictors (P < 0.05) of each indicator. RESULTS: For both
      platelets and neutrophils, pooled and separate analyses of (90)Y-ibritumomab
      tiuxetan and (131)I-tositumomab data yielded the time elapsed since the last
      chemotherapy as the only significant predictor of the percentage baseline at
      nadir. The extent of bone marrow involvement was not a significant factor in this
      study, possibly because of the short time elapsed since the last chemotherapy of
      the 7 patients with bone marrow involvement. Because both treatments were
      designed to deliver a comparable bone marrow dose, this factor also was not
      significant. None of the 14 factors considered was predictive of the time to
      nadir. The R(2) value for the model predicting percentage baseline at nadir was
      0.60 for platelets and 0.40 for neutrophils. This model predicted the platelet
      and neutrophil toxicity grade to within +/-1 for 28 and 30 of the 32 patients,
      respectively. For the 7 patients predicted with grade I thrombocytopenia, 6 of
      whom had actual grade I-II, dosing might be increased to improve treatment
      efficacy. CONCLUSION: The elapsed time since the last chemotherapy can be used to
      predict hematologic toxicity and customize the current dosing method in
      radioimmunotherapy.

PMID- 21098797
TI  - What do our patients understand about their trial participation? Assessing
      patients' understanding of their informed consent consultation about randomised
      clinical trials.
AB  - BACKGROUND: Ethically, informed consent regarding randomised controlled trials
      (RCTs) should be understandable to patients. The patients can then give free
      consent or decline to participate in a RCT. Little is known about what patients
      really understand in consultations about RCTs. METHODS: Cancer patients who were
      asked to participate in a randomised trial were surveyed using a semi
      standardised interview developed by the authors. The interview addresses
      understanding, satisfaction and needs of the patients. The sample included eight
      patients who participated in a trial and two who declined. The data were analysed
      on the basis of Mayring's qualitative analysis. RESULTS: Patients' understanding
      of informed consent was less developed than anticipated, especially concerning
      key elements such as randomisation, content and procedure of RCTs. Analysing the
      result about satisfaction of the patients, most of the patients described their
      consultations as hectic and without advance notice. Health limitations due to
      cancer played a decisive role. However, most of the patients perceived their
      physician to be sympathetic. Analysing the needs of patients, they ask for a
      clear informed consent consultation with enough time and adequate advance notice.
      CONCLUSION: This study fills an important empirical research gap of what is
      ethically demanded in an RCT consultation and what is really understood by
      patients. The qualitative approach enabled us to obtain new results about cancer
      patients' understanding of informed consent, to clarify patients' needs and to
      develop new ideas to optimise the informed consent.

PMID- 21098796
TI  - In vivo quantification of human serotonin 1A receptor using 11C-CUMI-101, an
      agonist PET radiotracer.
AB  - The serotonin (5-hydroxytryptamine, or 5-HT) type 1A receptor (5-HT(1A)R) is
      implicated in the pathophysiology of numerous neuropsychiatric disorders. We have
      published the initial evaluation and reproducibility in vivo of [O-methyl-(11)C]2
      (4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine
      3,5(2H,4H)dione ((11)C-CUMI-101), a novel 5-HT(1A) agonist radiotracer, in Papio
      anubis. Here, we report the optimal modeling parameters of (11)C-CUMI-101 for
      human PET studies. METHODS: PET scans were obtained for 7 adult human volunteers.
      (11)C-CUMI-101 was injected as an intravenous bolus, and emission data were
      collected for 120 min in 3-dimensional mode. We evaluated 10 different models
      using metabolite-corrected arterial input functions or reference region
      approaches and several outcome measures. RESULTS: When using binding potential
      (BP(F) = B(avail)/K(D) [total available receptor concentration divided by the
      equilibrium dissociation constant]) as the outcome measure, the likelihood
      estimation in the graphical analysis (LEGA) model performed slightly better than
      the other methods evaluated at full scan duration. The average test-retest
      percentage difference was 9.90% +/- 5.60%. When using BP(ND) (BP(ND) = f(nd) *
      B(avail)/K(D); BP(ND) equals the product of BP(F) and f(nd) [free fraction in the
      nondisplaceable compartment]), the simplified reference tissue method (SRTM)
      achieved the lowest percentage difference and smallest bias when compared with
      nondisplaceable binding potential obtained from LEGA using the metabolite
      corrected plasma input function (r(2) = 0.99; slope = 0.92). The time-stability
      analysis indicates that a 120-min scan is sufficient for the stable estimation of
      outcome measures. Voxel results were comparable to region-of-interest-based
      analysis, with higher spatial resolution. CONCLUSION: On the basis of its
      measurable and stable free fraction, high affinity and selectivity, good blood
      brain barrier permeability, and plasma and brain kinetics, (11)C-CUMI-101 is
      suitable for the imaging of high-affinity 5-HT(1A) binding in humans.

PMID- 21098798
TI  - Handlebar hernia in children.
AB  - Handlebar hernia is a rare form of traumatic abdominal wall hernia usually
      occurring in children. As the name suggests, it results from the blunt impact of
      a handlebar after a fall from a bicycle. A classic case is described of such a
      hernia occurring in a 14-year-old boy who presented with minimal external signs
      of injury, but was found to have significant traumatic disruption to the
      abdominal wall musculature and peritoneum, requiring surgical repair. A review of
      the English literature found only 25 cases of handlebar hernias in children less
      than 16 years of age. The average age is 9 years, and two-thirds of cases occur
      in boys. The frequency of associated visceral injury is low. The majority of
      reported cases were managed with surgical exploration and simple suture repair.
      Despite minimal signs on examination, the history should raise suspicion of
      significant underlying muscular disruption.

PMID- 21098799
TI  - The use of propofol for procedural sedation and analgesia in the emergency
      department: a comparison with midazolam.
AB  - INTRODUCTION: This study aimed to determine the effectiveness of propofol as an
      alternative agent for procedural sedation and analgesia (PSA) in the emergency
      department (ED) and to make a comparison between two different sedative (propofol
      vs midazolam) drugs used in combination with fentanyl. OBJECTIVES: To compare
      outcomes between a combination of fentanyl and propofol with fentanyl and
      midazolam in patients during and after PSA. METHODOLOGY: A randomised single
      blinded control trial carried out in the ED of a university hospital. 40 patients
      were randomly allocated equally into two groups: group A, 20 subjects received
      intravenous fentanyl 3 MUg/kg as a bolus dose and a titration maximum bolus dose
      of propofol 1 mg/kg followed by a maximum titration top-up of 0.5 mg/kg if
      needed; group B, 20 subjects received intravenous fentanyl 3 MUg/kg as a bolus
      dose and a titration maximum bolus dose of midazolam 0.1 mg/kg and a maximum
      titration top-up of 0.1 mg/kg if needed. The target sedation level was a Ramsay
      score of 3 or 4. Outcomes included the presence of any adverse events related to
      PSA and time to discharge. The Mann-Whitney U test was used to compare the two
      groups. RESULTS: None of the patients developed any significant adverse events
      during and after procedures. The mean length of stay in the propofol and
      midazolam groups was 29.25 (11.03) and 71.75 (60.64) min, respectively (p<0.001).
      CONCLUSION: Both propofol and midazolam given at the recommended doses were
      equally safe and effective for PSA in the ED. The propofol group was discharged
      much earlier than to the midazolam group.

PMID- 21098800
TI  - Fatal disconnection of a ventricular assist device in an out-of-hospital setting.

PMID- 21098801
TI  - Working the night shift: evidence-based practice?

PMID- 21098802
TI  - Twelve-monthly versus six-monthly radiological screening for active case-finding
      of tuberculosis: a randomised controlled trial.
AB  - BACKGROUND: The incidence of tuberculosis has increased among South African gold
      miners despite comprehensive control programmes, including a radiological
      screening programme. No data are available as to the optimal frequency of
      screening. The aim of this study was to compare 6-monthly and 12-monthly
      radiological screening for active tuberculosis case-finding. METHODS: Employees
      of a gold mining company were randomly assigned to the control arm (screening at
      baseline, 12 and 24 months) or the intervention arm (additional 'intervention'
      radiographs at 6 and 18 months after baseline). Study outcomes included
      proportion of tuberculosis cases detected by screening, proportion smear
      positive, extent of disease and mortality. RESULTS: 22,634 miners were
      randomised. Compared with 12-monthly screening, 6-monthly screening detected more
      tuberculosis suspects but not more cases, partly due to greater attrition between
      screening and further investigation after 'intervention' compared with routine
      radiographs. Tuberculosis cases detected in the 6-monthly versus the 12-monthly
      screening arm had less extensive disease (p=0.05) and a lower tuberculosis
      specific mortality (death on tuberculosis treatment) (2.1 and 2.8 per 1000 person
      years respectively, HR 0.73, 95% CI 0.50 to 1.08, p=0.1), which was most marked
      in the first 2 months of treatment (HR 0.48, 95% CI 0.23 to 0.98, p=0.04) when
      death from tuberculosis is most likely. DISCUSSION: In settings with a high
      prevalence of HIV and tuberculosis despite standard tuberculosis control
      measures, more frequent case-finding may reduce the extent of disease,
      tuberculosis mortality and tuberculosis transmission through earlier detection of
      active tuberculosis cases. To be effective, however, all tuberculosis suspects
      identified through screening must be investigated for tuberculosis.

PMID- 21098803
TI  - Seasonality and attendance at a pulmonary rehabilitation programme.

PMID- 21098804
TI  - Induced cortical gamma-band oscillations reflect cognitive control elicited by
      implicit probability cues in the preparing-to-overcome-prepotency (POP) task.
AB  - Previous research suggests that synchronous cortical gamma-band oscillations
      reflect the implementation of cognitive control in anticipation of the need to
      overcome prepotent responses. These studies often require participants to link
      task instructions with task cues signaling the need (or lack thereof) for
      cognitive control. Thus, the oscillatory response elicited by these cues may also
      reflect the implementation of explicit task instructions. The aim of this
      research was to determine whether gamma-band oscillations would also be increased
      in preparation for cognitive control when the need for that control was only made
      implicitly available to the participant. Using a task-ambiguous cue to indicate
      the position of a subsequent probe stimulus, we manipulated the need for
      cognitive control by varying the probability of high- and low-control probes
      appearing in each of two positions. Results show that participants developed the
      anticipated expectancies regarding probe identity in the two positions and that
      the anticipation of a high-control probe was associated with an increase in the
      power of induced cortical gamma band over frontal scalp recording sites.

PMID- 21098805
TI  - Absorbed in the task: Personality measures predict engagement during task
      performance as tracked by error negativity and asymmetrical frontal activity.
AB  - We hypothesized that interactions between traits and context predict task
      engagement, as measured by the amplitude of the error-related negativity (ERN),
      performance, and relative frontal activity asymmetry (RFA). In Study 1, we found
      that drive for reward, absorption, and constraint independently predicted self
      reported persistence. We hypothesized that, during a prolonged monotonous task,
      absorption would predict initial ERN amplitudes, constraint would delay declines
      in ERN amplitudes and deterioration of performance, and drive for reward would
      predict left RFA when a reward could be obtained. Study 2, employing EEG
      recordings, confirmed our predictions. The results showed that most traits that
      have in previous research been related to ERN amplitudes have a relationship with
      the motivational trait persistence in common. In addition, trait-context
      combinations that are likely associated with increased engagement predict larger
      ERN amplitudes and RFA. Together, these results support the hypothesis that
      engagement may be a common underlying factor predicting ERN amplitude.

PMID- 21098806
TI  - Planning not to do something: Does intending not to do something activate
      associated sensory consequences?
AB  - The present fMRI study investigated the central assumptions of ideomotor theory
      that actions become associated with their sensory consequences. Furthermore, we
      tested whether sensory effects can also become associated with the voluntary
      omission of an action. In a training phase, participants had to decide between
      executing an action and not executing it. Both decisions were followed by a
      specific effect tone. In the test phase, the participants had to carry out
      actions without hearing the effect tone. They either had to decide whether to
      execute an action or not or were instructed to execute an action or not. Our
      results reveal an increased activity in the auditory cortex elicited by responses
      that formerly elicited a tone-namely, self-chosen actions and self-chosen
      nonactions. Moreover, we found binding effects for stimulus-cued actions, but not
      for stimulus-cued nonactions. These findings support ideomotor theory by showing
      that a link exists between actions and their effects. Furthermore, our data
      demonstrate on a neural level that effect tones can become associated with
      intentionally not acting, therewith supporting the idea of a binding between the
      voluntary omission of an action and its effects in the environment.

PMID- 21098807
TI  - Striatal sensitivity to personal responsibility in a regret-based decision-making
      task.
AB  - Regret and relief are complex emotional states associated with the counterfactual
      processing of nonobtained outcomes in a decision-making situation. In the "actor
      effect," a sense of agency and personal responsibility is thought to heighten
      these emotions. Using fMRI, we scanned volunteers (n = 22) as they played a task
      involving choices between two wheel-of-fortune gambles. We examined how neural
      responses to counterfactual outcomes were modulated by giving subjects the
      opportunity to change their minds, as a manipulation of personal responsibility.
      Satisfaction ratings to the outcomes were highly sensitive to the difference
      between the obtained and nonobtained outcome, and ratings following losses were
      lower on trials with the opportunity to change one's mind. Outcome-related
      activity in the striatum and orbitofrontal cortex was positively related to the
      satisfaction ratings. The striatal response was modulated by the agency
      manipulation: Following losses, the striatal signal was significantly lower when
      the subject had the opportunity to change his/her mind. These results support the
      involvement of frontostriatal mechanisms in counterfactual thinking and highlight
      the sensitivity of the striatum to the effects of personal responsibility.

PMID- 21098808
TI  - Neural correlates of rumination in depression.
AB  - Rumination, or recursive self-focused thinking, has important implications for
      understanding the development and maintenance of depressive episodes. Rumination
      is associated with the worsening of negative mood states, greater affective
      responding to negative material, and increased access to negative memories. The
      present study was designed to use fMRI to examine neural aspects of rumination in
      depressed and healthy control individuals. We used a rumination induction task to
      assess differences in patterns of neural activation during ruminative self-focus
      as compared with a concrete distraction condition and with a novel abstract
      distraction condition in 14 participants who were diagnosed with major depressive
      disorder and 14 healthy control participants. Depressed participants exhibited
      increased activation in the orbitofrontal cortex, subgenual anterior cingulate,
      and dorsolateral prefrontal cortex as compared with healthy controls during
      rumination versus concrete distraction. Neural activity during rumination versus
      abstract distraction was greater for depressed than for control participants in
      the amygdala, rostral anterior cingulate/medial prefrontal cortex, dorsolateral
      prefrontal cortex, posterior cingulate, and parahippocampus. These findings
      indicate that ruminative self-focus is associated with enhanced recruitment of
      limbic and medial and dorsolateral prefrontal regions in depression. Supplemental
      materials for this article may be downloaded from http://cabn.psychonomic
      journals.org/content/supplemental.

PMID- 21098809
TI  - Anxiety not only increases, but also alters early error-monitoring functions.
AB  - Anxiety has profound influences on a wide range of cognitive processes, including
      action monitoring. Event-related brain potential (ERP) studies have shown that
      anxiety can boost early error detection mechanisms, as reflected by an enhanced
      error-related negativity (ERN) following errors in high-anxious, as compared with
      low-anxious, participants. This observation is consistent with the assumption of
      a gain control mechanism exerted by anxiety onto error-related brain responses
      within the dorsal anterior cingulate cortex (ACC). However, whether anxiety
      simply enhances or, rather, alters early error detection mechanisms remains
      unsolved. In this study, we compared the performance of low- versus high-trait
      anxious participants during a go/no-go task while high-density EEG was recorded.
      The two groups showed comparable behavioral performance, although levels of state
      anxiety increased following the task for high-anxious participants only. ERP
      results confirmed that the ERN/Ne to errors was enhanced for high-anxious,
      relative to low-anxious, participants. However, complementary topographic
      analyses revealed that the scalp map of the ERN/Ne was not identical between the
      two groups, suggesting that anxiety did not merely increase early error detection
      mechanisms, but also led to a qualitative change in the early appraisal of
      errors. Inverse solution results confirmed a shift within the ACC for the
      localization of neural generators underlying the ERN/Ne scalp map in high-anxious
      participants, corroborating the assumption of an early effect of anxiety on early
      error-monitoring functions. These results shed new light on the dynamic interplay
      between anxiety and error-monitoring functions in the human brain.

PMID- 21098810
TI  - "Feeling" the pain of those who are different from us: Modulation of EEG in the
      mu/alpha range.
AB  - We explored how apparently painful stimuli and the ability to identify with the
      person on whom the pain is inflicted modulate EEG suppression in the mu/alpha
      range (8-12 Hz). In a 2 * 2 design, we presented pictures of hands either
      experiencing needle pricks or being touched by a Q-tip. In the dissimilar-other
      condition, the hand was assigned to a patient suffering from a neurological
      disease in which Q-tips inflicted pain, whereas needle pricks did not. In the
      similar-other condition, the hand was assigned to a patient who responded to
      stimulation in the same way as the healthy participant. Participants were
      instructed to imagine the feeling of the person whose hand was shown and to
      evaluate his or her affective state. Pain conditions elicited greater EEG
      suppression than did nonpain conditions, particularly over frontocentral regions.
      Moreover, an interaction between pain and similarity revealed that for similar
      others, the pain effect was significant, whereas in the dissimilar-other group,
      suppression was equally large in the pain and no-pain conditions. We conclude
      that mu/alpha suppression is elicited both automatically, by observing a
      situation that is potentially painful for the observer, and by empathy for pain,
      even if the other person is different from oneself.

PMID- 21098812
TI  - Event-related brain potentials and the efficiency of visual search for vertically
      and horizontally oriented stimuli.
AB  - Reports that visual search is more efficient for vertically than for horizontally
      shaded objects suggested that search is influenced by a priori knowledge about
      the source of light. In this study, we examined search for targets defined by the
      orientation of luminance gradients and measured event-related brain potentials
      (ERPs). In Experiment 1, we examined search for stimuli that comprised gradual
      luminance differences. Response times showed the expected orientation anisotropy
      effect. ERP amplitudes in the P1 latency range were slightly more positive in
      response to horizontally oriented stimuli, whereas P3 amplitudes were more
      positive in response to nonsingleton vertically oriented stimuli. Experiment 2
      compared search for stimuli that comprised gradual versus step differences in
      luminance. All the anisotropies that we observed in Experiment 1 could be
      replicated in Experiment 2. Moreover, these anisotropies were not dependent on
      the type of the luminance gradient. This finding is inconsistent with the view
      that search efficiency is influenced by a priori knowledge about the source of
      light. The behavioral and electrophysiological data are consistent with a context
      model of visual search. We propose that contextual modulation reduces redundancy
      and contributes to computing the saliency of visual information by implementing
      divisive normalization and multiplicative filtering.

PMID- 21098811
TI  - On the temporal organization of facial identity and expression analysis:
      Inferences from event-related brain potentials.
AB  - In the present study, behavioral and electrophysiological markers of information
      processing-the lateralized readiness potential, the N170, and the P300-were
      recorded in order to assess the functional and temporal organization of facial
      identity and expression processing. A two-choice go/no-go task was used in which
      facial expression (happy vs. angry) determined response hand and response
      execution depended on facial familiarity (familiar vs. unfamiliar). The duration
      of facial identity and expression processing was manipulated in separate
      experiments. Together, the present findings in measures of overt and covert
      response activation indicate that facial identity is analyzed in parallel with,
      and typically somewhat faster than, facial expression. These data support a
      parallel model of face perception that assumes partial output from facial
      identity and expression processes to motor activation processes.

PMID- 21098813
TI  - Holistic processing of musical notation: Dissociating failures of selective
      attention in experts and novices.
AB  - Holistic processing (i.e., the tendency to process objects as wholes) is
      associated with face perception and also with expertise individuating novel
      objects. Surprisingly, recent work also reveals holistic effects in novice
      observers. It is unclear whether the same mechanisms support holistic effects in
      experts and in novices. In the present study, we measured holistic processing of
      music sequences using a selective attention task in participants who vary in
      music-reading expertise. We found that holistic effects were strategic in novices
      but were relatively automatic in experts. Correlational analyses revealed that
      individual holistic effects were predicted by both individual music-reading
      ability and neural responses for musical notation in the right fusiform face area
      (rFFA), but in opposite directions for experts and novices, suggesting that
      holistic effects in the two groups may be of different natures. To characterize
      expert perception, it is important not only to measure the tendency to process
      objects as wholes, but also to test whether this effect is dependent on task
      constraints.

PMID- 21098814
TI  - Position of phonetic components may influence how written words are processed in
      the brain: Evidence from Chinese phonetic compound pronunciation.
AB  - Previous studies have shown a right-visual-field (RVF)/left-hemisphere (LH)
      advantage in Chinese phonetic compound pronunciation. Here, we contrast the
      processing of two phonetic compound types: a dominant structure in which a
      semantic component appears on the left and a phonetic component on the right (SP
      characters), and a minority structure with the opposite arrangement (PS
      characters). We show that this RVF/LH advantage was observed only in SP character
      pronunciation, but not in PS character pronunciation. This result suggests that
      SP character processing is more LH lateralized than is PS character processing
      and is consistent with corresponding ERP N170 data. This effect may be due to the
      dominance of SP characters in the lexicon, which makes readers opt to obtain
      phonological information from the right of the characters. This study thus shows
      that the overall information distribution of word components in the lexicon may
      influence how written words are processed in the brain. Supplemental materials
      for this article may be downloaded from http://cabn.psychonomic
      journals.org/content/supplemental.

PMID- 21098816
TI  - Risk of serious injury for young baseball pitchers: a 10-year prospective study.
AB  - BACKGROUND: The risk of elbow or shoulder injury for young baseball pitchers is
      unknown. PURPOSE/ HYPOTHESIS: The purpose of this study was to quantify the
      cumulative incidence of throwing injuries in young baseball pitchers who were
      followed for 10 years. Three hypotheses were tested: Increased amount of
      pitching, throwing curveballs at a young age, and concomitantly playing catcher
      increase a young pitcher's risk of injury. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: In sum, 481 youth pitchers (aged 9 to 14 years) were
      enrolled in a 10-year follow-up study. Participants were interviewed annually.
      Injury was defined as elbow surgery, shoulder surgery, or retirement due to
      throwing injury. Fisher exact test compared the risk of injury between
      participants who pitched at least 4 years during the study and those who pitched
      less. Fisher exact tests were used to investigate risks of injury for pitching
      more than 100 innings in at least 1 calendar year, starting curveballs before age
      13 years, and playing catcher for at least 3 years. RESULTS: The cumulative
      incidence of injury was 5.0%. Participants who pitched more than 100 innings in a
      year were 3.5 times more likely to be injured (95% confidence interval = 1.16 to
      10.44). Pitchers who concomitantly played catcher seemed to be injured more
      frequently, but this trend was not significant with the study sample size.
      CONCLUSION: Pitching more than 100 innings in a year significantly increases risk
      of injury. Playing catcher appears to increase a pitcher's risk of injury,
      although this trend is not significant. The study was unable to demonstrate that
      curveballs before age 13 years increase risk of injury. CLINICAL RELEVANCE: The
      risk of a youth pitcher sustaining a serious throwing injury within 10 years is
      5%. Limiting the number of innings pitched per year may reduce the risk of
      injury. Young baseball pitchers are encouraged to play other positions as well
      but might avoid playing catcher.

PMID- 21098817
TI  - Pathologic tibia/fibula fracture through a suture button screw tract: case
      report.

PMID- 21098818
TI  - Return to the preinjury level of competitive sport after anterior cruciate
      ligament reconstruction surgery: two-thirds of patients have not returned by 12
      months after surgery.
AB  - BACKGROUND: An athlete's desire to return to sport after anterior cruciate
      ligament (ACL) injury is a major indication for ACL reconstruction surgery.
      Typical clearance to return is 6 to 12 months postoperatively. PURPOSE: To
      investigate the return-to-sport rate and participation level of a large cohort at
      12 months after ACL reconstruction surgery. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Data were analyzed for 503 patients who participated in
      competitive-level Australian football, basketball, netball, or soccer after ACL
      reconstruction surgery using a quadruple-strand hamstring autograft. Inclusion
      criteria included participation in competitive sport before the ACL injury and
      clearance from the orthopaedic surgeon to return to sport postoperatively.
      Patients completed a self-report questionnaire regarding preoperative and
      postoperative sports participation and the Cincinnati Sports Activity Scale. The
      International Knee Documentation Committee (IKDC) knee evaluation form and hop
      tests were used to evaluate knee function. RESULTS: Sixty-seven percent of
      patients attempted some form of sports activity by 12 months postoperatively; 33%
      attempted competitive sport. Of those who did not attempt any sports activity by
      12 months, 47% indicated that they were planning to return. Men were
      significantly more likely than women to return. Patients who played sports with a
      seasonal competition, versus a year-round competition, were significantly more
      likely to return by 12 months. Patients with normal postoperative knee function
      (IKDC category A), versus those with nearly normal function (IKDC category B),
      were no more likely to return, but patients with good hop test results (>=85%
      limb symmetry index) were more likely to return than patients with poor results
      (<85%). CONCLUSION: People may require a longer postoperative rehabilitation
      period than that typically advocated to facilitate a successful return to
      competitive sport after ACL reconstruction surgery. The relationship between
      postoperative knee function and return-to-sport outcomes at 12 months after
      surgery was inconclusive.

PMID- 21098819
TI  - A prospective randomized study comparing arthroscopic single-bundle and double
      bundle posterior cruciate ligament reconstructions preserving remnant fibers.
AB  - BACKGROUND: Several controversies exist regarding the superiority of double
      bundle (DB) posterior cruciate ligament (PCL) reconstruction versus single-bundle
      (SB) reconstruction, although DB reconstruction has been shown to restore the
      intact knee kinematics more closely than SB reconstruction. HYPOTHESIS: Double
      bundle PCL reconstruction will present better results than SB reconstruction in
      postoperative outcomes. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 2. METHODS: The authors prospectively analyzed 25 cases of SB
      reconstruction and 28 cases of DB reconstruction using Achilles tendon allograft
      with a minimum 2-year follow-up. They compared preoperative and postoperative
      range of motion, posterior stability by posterior stress radiography, Tegner
      activity score, Lysholm score, and International Knee Documentation Committee
      (IKDC) subjective knee evaluation form and knee examination form between the 2
      groups. RESULTS: There was no difference in range of motion, Tegner activity
      score, Lysholm score, and IKDC subjective knee evaluation form between the 2
      groups at last follow-up. The side-to-side difference in posterior translation
      significantly improved in both groups. There was no preoperative difference in
      posterior instability between the groups but a significant difference at last
      follow-up. On the IKDC knee examination form, the DB reconstruction group
      presented better results in grade distribution. CONCLUSION: The DB reconstruction
      for PCL ruptures using the Achilles allograft showed better results in posterior
      stability and IKDC knee examination form than the SB reconstruction did. Although
      the difference of 1.4 mm in posterior stability was statistically significant, it
      is unclear that DB reconstruction is definitely superior to SB reconstruction
      clinically and functionally because there was no difference in the subjective
      scores.

PMID- 21098820
TI  - Clinical and radiographic predictors of intra-articular hip disease in
      arthroscopy.
AB  - BACKGROUND: The arthroscopic treatment of intra-articular hip disease and
      associated structural abnormalities continues to evolve. Nevertheless,
      contemporary diagnostic tools have significant limitations in predicting severity
      of disease preoperatively. HYPOTHESIS: Clinical characteristics and radiographic
      parameters correlate with and predict intra-articular disease patterns in
      patients undergoing hip arthroscopy. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: In sum, 355 hips in 338 patients undergoing hip arthroscopy
      by a single surgeon were retrospectively reviewed. Clinical characteristics and
      radiographic findings (on anteroposterior pelvis and frog lateral radiographs) of
      mild dysplasia, cam, and pincer-type femoroacetabular impingement were compared
      with intraoperative labral and chondral disease patterns. RESULTS: Labral tears
      were present in 90.1% of hips, and acetabular cartilage lesions were present in
      67.3%, including 41.7% with grade 3 or 4 chondromalacia. Multivariate logistic
      regression analysis found male sex, older age (<30, 30-50, >50 years old), Tonnis
      osteoarthritis grade, and alpha angle >50 degrees  on frog lateral radiograph to
      be independently associated with increased risk of grade 3 or 4 acetabular
      chondromalacia (all P < .001). Insidious onset of pain (in contrast to acute
      onset) was independently associated with the presence of acetabular
      chondromalacia (P = .002). Cam-type femoroacetabular impingement (alpha angle >50
      degrees ) was strongly associated with more severe labral disease (P < .001).
      Findings of acetabular dysplasia and pincer femoroacetabular impingement did not
      remain significantly associated with acetabular chondral disease in the
      multivariate analysis. CONCLUSION: Several clinical and radiographic
      characteristics--most notably, male sex, older age, Tonnis grade, and elevated
      alpha angle--are associated with more severe intra-articular hip disease. The
      recognition of these associations between clinical and radiographic
      characteristics and hip disease patterns is important for patient selection,
      surgical planning, and patient counseling.

PMID- 21098822
TI  - The recidivism rates of female sexual offenders are low: a meta-analysis.
AB  - This study examined the recidivism rates of female sexual offenders. A meta
      analysis of 10 studies (2,490 offenders; average follow-up 6.5 years) showed that
      female sexual offenders have extremely low rates of sexual recidivism (less than
      3%). The recidivism rates for violent (including sexual) offences and for any
      type of crime were predictably higher than the recidivism rates for sexual
      offences but still lower than the recidivism rates of male sexual offenders.
      These findings indicate the need for distinct policies and procedures for
      assessing and managing the risk of male and female sexual offenders. Risk
      assessment tools developed specifically for male sexual offenders would be
      expected to substantially overestimate the recidivism risk of female sexual
      offenders.

PMID- 21098823
TI  - Recent research (N = 9,305) underscores the importance of using age-stratified
      actuarial tables in sex offender risk assessments.
AB  - A useful understanding of the relationship between age, actuarial scores, and
      sexual recidivism can be obtained by comparing the entries in equivalent cells
      from "age-stratified" actuarial tables. This article reports the compilation of
      the first multisample age-stratified table of sexual recidivism rates, referred
      to as the "multisample age-stratified table of sexual recidivism rates (MATS-1),"
      from recent research on Static-99 and another actuarial known as the Automated
      Sexual Recidivism Scale. The MATS-1 validates the "age invariance effect" that
      the risk of sexual recidivism declines with advancing age and shows that age
      restricted tables underestimate risk for younger offenders and overestimate risk
      for older offenders. Based on data from more than 9,000 sex offenders, our
      conclusion is that evaluators should report recidivism estimates from age
      stratified tables when they are assessing sexual recidivism risk, particularly
      when evaluating the aging sex offender.

PMID- 21098824
TI  - Molecular phylogenies disprove a hypothesized C4 reversion in Eragrostis walteri
      (Poaceae).
AB  - BACKGROUND AND AIMS: The main assemblage of the grass subfamily Chloridoideae is
      the largest known clade of C(4) plant species, with the notable exception of
      Eragrostis walteri Pilg., whose leaf anatomy has been described as typical of
      C(3) plants. Eragrostis walteri is therefore classically hypothesized to
      represent an exceptional example of evolutionary reversion from C(4) to C(3)
      photosynthesis. Here this hypothesis is tested by verifying the photosynthetic
      type of E. walteri and its classification. METHODS: Carbon isotope analyses were
      used to determine the photosynthetic pathway of several E. walteri accessions,
      and phylogenetic analyses of plastid rbcL and ndhF and nuclear internal
      transcribed spacer DNA sequences were used to establish the phylogenetic position
      of the species. RESULTS: Carbon isotope analyses confirmed that E. walteri is a
      C(3) plant. However, phylogenetic analyses demonstrate that this species has been
      misclassified, showing that E. walteri is positioned outside Chloridoideae in
      Arundinoideae, a subfamily comprised entirely of C(3) species. CONCLUSIONS: The
      long-standing hypothesis of C(4) to C(3) reversion in E. walteri is rejected, and
      the classification of this species needs to be re-evaluated.

PMID- 21098825
TI  - Reliability of perceived neighbourhood conditions and the effects of measurement
      error on self-rated health across urban and rural neighbourhoods.
AB  - BACKGROUND: Limited psychometric research has examined the reliability of self
      reported measures of neighbourhood conditions, the effect of measurement error on
      associations between neighbourhood conditions and health, and potential
      differences in the reliabilities between neighbourhood strata (urban vs rural and
      low vs high poverty). We assessed overall and stratified reliability of self
      reported perceived neighbourhood conditions using five scales (social and
      physical disorder, social control, social cohesion, fear) and four single items
      (multidimensional neighbouring). We also assessed measurement error-corrected
      associations of these conditions with self-rated health. METHODS: Using random
      digit dialling, 367 women without breast cancer (matched controls from a larger
      study) were interviewed twice, 2-3 weeks apart. Test-retest (intraclass
      correlation coefficients (ICC)/weighted kappa) and internal consistency
      reliability (Cronbach's alpha) were assessed. Differences in reliability across
      neighbourhood strata were tested using bootstrap methods. Regression calibration
      corrected estimates for measurement error. RESULTS: All measures demonstrated
      satisfactory internal consistency (alpha >= 0.70) and either moderate
      (ICC/kappa=0.41-0.60) or substantial (ICC/kappa=0.61-0.80) test-retest
      reliability in the full sample. Internal consistency did not differ by
      neighbourhood strata. Test-retest reliability was significantly lower among rural
      (vs urban) residents for two scales (social control, physical disorder) and two
      multidimensional neighbouring items; test-retest reliability was higher for
      physical disorder and lower for one multidimensional neighbouring item among the
      high (vs low) poverty strata. After measurement error correction, the magnitude
      of associations between neighbourhood conditions and self-rated health were
      larger, particularly in the rural population. CONCLUSION: Research is needed to
      develop and test reliable measures of perceived neighbourhood conditions relevant
      to the health of rural populations.

PMID- 21098827
TI  - Individual and organisational determinants of use of ergonomic devices in
      healthcare.
AB  - OBJECTIVE: This study aims to identify individual and organisational determinants
      associated with the use of ergonomic devices during patient handling activities.
      METHODS: This cross-sectional study was carried out in 19 nursing homes and 19
      hospitals. The use of ergonomic devices was assessed through real-time
      observations in the workplace. Individual barriers to ergonomic device use were
      identified by structured interviews with nurses and organisational barriers were
      identified using questionnaires completed by supervisors and managers.
      Multivariate logistic analysis with generalised estimating equations for repeated
      measurement was used to estimate determinants of ergonomic device use. RESULTS:
      247 nurses performed 670 patient handling activities that required the use of an
      ergonomic device. Ergonomic devices were used 68% of the times they were deemed
      necessary in nursing homes and 59% in hospitals. Determinants of lifting device
      use were nurses' motivation (OR 1.96), the presence of back complaints in the
      past 12months (OR 1.77) and the inclusion in care protocols of strict guidance on
      the required use of ergonomic devices (OR 2.49). The organisational factors
      convenience and easily accessible, management support and supportive management
      climate were associated with these determinants. No associations were found with
      other ergonomic devices. CONCLUSIONS: The use of lifting devices was higher in
      nursing homes than in hospitals. Individual and organisational factors seem to
      play a substantial role in the successful implementation of lifting devices in
      healthcare.

PMID- 21098826
TI  - Childhood social class and adult adiposity and blood-pressure trajectories 36-53
      years: gender-specific results from a British birth cohort.
AB  - BACKGROUND: In this study, the authors investigate gender-specific effects of
      childhood socio-economic position (SEP) on adiposity and blood pressure at three
      time points in adulthood. METHODS: Mixed models were used to assess the
      association of childhood SEP with body mass index (BMI), waist circumference,
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) at ages 36, 43
      and 53 years in a British birth cohort. RESULTS: The adverse effect of lower
      childhood SEP on adiposity increased between ages 36 and 53 years in women (BMI:
      trend test: p=0.03) and remained stable in men, but the opposite was seen for
      SBP, where inequalities increased in men (p=0.01). Childhood SEP inequalities in
      DBP were stable with age in both men and women. Educational attainment mediated
      some but not all of the effects of childhood SEP on adiposity and SBP, and their
      rate of change; adult social class was a less important mediator. CONCLUSION:
      Childhood SEP is important for adult adiposity and blood pressure across midlife,
      especially for BMI in women and for blood pressure in men. Thus, pathways to
      adult health differ for men and women, and public health policies aimed at
      reducing social inequalities need to start early in life and take account of
      gender.

PMID- 21098828
TI  - Pulmonary tuberculosis infection among workers in the informal public transport
      sector in Lima, Peru.
AB  - BACKGROUND: Because a strong association was observed between pulmonary
      tuberculosis (TB) and the use of public transport, increasing with duration of
      journey, a study was carried out to assess infection by Mycobacterium
      tuberculosis and working conditions among workers in this sector. METHODS: A
      cross-sectional study was conducted between June and September 2008. A total of
      104 workers from two public transport minibus ('combi') cooperatives covering
      marginal areas of the Ate-Vitarte district in Lima were interviewed. Demographic
      and occupational details were collected as well as prior family and personal
      history of TB and BCG vaccination. The tuberculin skin test (TST) was
      administered to each study subject and an induration of >= 10 mm was considered
      positive. Statistical analysis was based on logistic models, ORs and their 95%
      CIs. RESULTS: TST results were obtained for 70.2% (n=73), of whom 76.6% (n=56)
      were positive. Positivity was significantly associated with those who had worked
      for more than 2 years (crude OR 11.04; 95% CI 3.17 to 38.43) and more than 60
      h/week (crude OR 9.8; 95% CI 2.85 to 33.72). These associations remained
      significant in a multivariate model as well. CONCLUSION: The association observed
      between years of working and weekly work burden among minibus workers suggests an
      occupational risk in service jobs in low-income countries with high TB
      prevalence. Consequently, other types of users are at increased risk for TB
      infection, with a causal relationship between effect and duration of exposure.

PMID- 21098829
TI  - Relationships between occupational history and serum concentrations of
      organochlorine compounds in exocrine pancreatic cancer.
AB  - BACKGROUND: Previous studies investigating associations between occupational
      history and risk of exocrine pancreatic cancer (EPC) did not use biomarkers of
      exposure. The only two studies that measured internal concentrations of
      organochlorine compounds (OCs) in EPC did not analyse their relationship with
      occupation. OBJECTIVE: To analyse the relationship between occupational history
      and blood concentrations of seven OCs in patients with EPC. METHODS: Incident
      cases of EPC were prospectively identified, and during hospital admission were
      interviewed face-to-face on occupational history and life-style factors (n =
      135). Occupations were coded according to the International Standard of
      Occupations 1988. Some occupational exposures were also assessed with the Finnish
      job-exposure matrix (Finjem). Serum concentrations of OCs were analysed by high
      resolution gas chromatography with electron-capture detection. RESULTS: Craftsmen
      and related trades workers had significantly higher concentrations of
      polychlorinated biphenyl (PCB) congeners 138, 153 and 180. Years worked in
      agriculture did not influence concentrations of p,p'-DDT, p,p'-DDE,
      hexachlorobenzene or beta-hexachlorocyclohexane. Subjects who ever worked in
      agriculture had lower concentrations of PCBs (all p < 0.05). Occupational
      exposure to lead, nickel and low frequency magnetic fields was significantly
      associated with higher concentrations of PCBs. CONCLUSIONS: Certain occupations
      were associated with higher concentrations of PCBs, suggesting that these
      compounds may account for some increased risks found in previous studies. The
      lack of association between work in agriculture and concentrations of OC
      pesticides is consistent with occupation playing a lesser role than diet in
      influencing OC concentrations. Occupational studies on the relationships among
      exposure to industrial agents and EPC risk may need to consider adjusting for
      exposure to PCBs.

PMID- 21098830
TI  - Reconstructing past occupational exposures: how reliable are women's reports of
      their partner's occupation?
AB  - OBJECTIVES: Most of the evidence on agreement between self- and proxy-reported
      occupational data comes from interview-based studies. The authors aimed to
      examine agreement between women's reports of their partner's occupation and their
      partner's own description using questionnaire-based data collected as a part of
      the prospective, population-based Avon Longitudinal Study of Parents and
      Children. METHODS: Information on present occupation was self-reported by women's
      partners and proxy-reported by women through questionnaires administered at 8 and
      21 months after the birth of a child. Job titles were coded to the Standard
      Occupational Classification (SOC2000) using software developed by the University
      of Warwick (Computer-Assisted Structured Coding Tool). The accuracy of proxy
      report was expressed as percentage agreement and kappa coefficients for four-,
      three- and two-digit SOC2000 codes obtained in automatic and semiautomatic
      (manually improved) coding modes. Data from 6016 couples at 8 months and 5232
      couples at 21 months postnatally were included in the analyses. RESULTS: The
      agreement between men's self-reported occupation and women's report of their
      partner's occupation in fully automatic coding mode at four-, three- and two
      digit code level was 65%, 71% and 77% at 8 months and 68%, 73% and 76% at 21
      months. The accuracy of agreement was slightly improved by semiautomatic coding
      of occupations: 73%/73%, 78%/77% and 83%/80% at 8/21 months respectively. While
      this suggests that women's description of their partners' occupation can be used
      as a valuable tool in epidemiological research where data from partners are not
      available, this study revealed no agreement between these young women and their
      partners at the two-digit level of SOC2000 coding in approximately one in five
      cases. CONCLUSION: Proxy reporting of occupation introduces a statistically
      significant degree of error in classification. The effects of occupational
      misclassification by proxy reporting in retrospective occupational
      epidemiological studies based on questionnaire data should be considered.

PMID- 21098831
TI  - Does the use of biofuels affect respiratory health among male Danish energy plant
      workers?
AB  - OBJECTIVES: To study asthma, respiratory symptoms and lung function among energy
      plant employees working with woodchip, straw or conventional fuel. METHODS:
      Respiratory symptoms in 138 woodchip workers, 94 straw workers and 107 control
      workers from 85 heating- or combined heating and power plants were collected by
      questionnaire. Spirometry, metacholine provocation tests and skin prick tests
      were performed on 310 workers. The work area concentrations of 'total dust'
      (n=181), airborne endotoxin (n=179), cultivable Aspergillus fumigatus (n=373) and
      cultivable fungi (n=406) were measured at each plant. Personal exposure was
      calculated from the time spent on different tasks and average work area
      exposures. RESULTS: Median (range) average personal exposures in biofuel plants
      were 0.05 (0 to 0.33) mg/m3 for 'total' dust and 3.5 (0 to 294) endotoxin
      units/m3 for endotoxin. Fungi were cultivated from filters (straw plants) or slit
      samplers (woodchip plants); the average personal exposures were 5.230*103 (118 to
      1.85*104) and 1.03*103 (364 to 5.01*103) colony-forming units/m3 respectively.
      Exposure levels were increased in biofuel plants compared with conventional
      plants. The prevalence of respiratory symptoms among conventional plant and
      biofuel plant workers was comparable, except for asthma symptoms among non
      smokers, which were higher among straw workers compared with controls (9.4 vs 0%,
      p<0.05). A trend for increasing respiratory symptoms with increasing endotoxin
      exposure was seen with ORs between 3.1 (1.1 to 8.8) (work-related nose symptoms)
      and 8.1 (1.5 to 44.4) (asthma symptoms) for the most exposed group. Associations
      between fungal exposure and respiratory symptoms were less clear but suggested
      cultivable fungi to be associated with asthma symptoms and work-related
      respiratory symptoms. No associations were seen between lung function and the
      level of endotoxin or fungal exposure. CONCLUSIONS: Working with biofuel at an
      energy plant does not generally enhance the prevalence of respiratory symptoms.
      However, the exposure level to micro-organisms has an impact on the occurrence of
      respiratory symptoms among biofuel workers.

PMID- 21098832
TI  - Long-term effects of an intervention on psychosocial work factors among
      healthcare professionals in a hospital setting.
AB  - OBJECTIVE: This study assessed the long-term effects of a workplace intervention
      aimed at reducing adverse psychosocial work factors (psychological demands,
      decision latitude, social support and effort-reward imbalance) and mental health
      problems among health care professionals in an acute care hospital. METHODS: A
      quasi-experimental design with a control group was used. Pre-intervention (71%
      response rate) and 3-year post-intervention measures (60% response rate) were
      collected by telephone interviews with validated instruments. RESULTS: Three
      years after the intervention, all adverse psychosocial factors except one were
      reduced in the experimental group, and the improvement was statistically
      significant for 5/9 factors: psychological demands, effort-reward imbalance,
      quality of work, physical load and emotional demands. In addition, all health
      indicators improved and 2/5 significantly: work-related and personal burnout. In
      the control hospital, three work factors improved significantly but two
      deteriorated significantly: decision latitude and social support. All health
      problem deteriorated, although not significantly, in the control hospital.
      Moreover, 3 years after the intervention, the mean of all adverse factors except
      one (psychological demands) and all health indicators was significantly more
      favourable in the experimental than the control hospital, after adjusting for pre
      intervention measures. CONCLUSION: These results support the long-term
      effectiveness of the intervention. The reduction in many psychosocial factors in
      the experimental hospital may have clinical significance since most health
      indicators also improved in this hospital. These results support the whole
      process of the intervention given that significant improvements in psychosocial
      factors and health problems were observed in the experimental hospital but not in
      the control hospital.

PMID- 21098833
TI  - Adieu from the editor--the last word.

PMID- 21098834
TI  - Officers' note--a word of thanks to Beryl Benacerraf.

PMID- 21098835
TI  - Thanks to Beryl Benacerraf from the AIUM.

PMID- 21098836
TI  - Thanks to Beryl Benacerraf from the deputy editors.

PMID- 21098837
TI  - Reflections on Beryl Benacerraf.

PMID- 21098838
TI  - A tribute to Beryl Benacerraf, Editor-in-Chief of the Journal of Ultrasound in
      Medicine, 2001-2010.

PMID- 21098839
TI  - Sonographic findings of high-grade and non-high-grade ductal carcinoma in situ of
      the breast.
AB  - OBJECTIVE: The purpose of this study was to differentiate between high-grade and
      non-high-grade ductal carcinoma in situ (DCIS) of the breast on sonography.
      METHODS: From October 2003 to August 2009, 76 DCIS lesions in 73 women who
      underwent sonography and mammography were included in this study. Lesions were
      confirmed by mastectomy, breast-conserving surgery, or surgical biopsy. Images
      were analyzed by 2 radiologists with consensus and were correlated with
      histologic grades. RESULTS: Of the 76 lesions, 44 were classified as high--grade
      and 32 as non-high-grade DCIS. Fifty-seven lesions (75.0%) were identified on
      sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal
      changes in 4, and architectural distortion in 3. All cases with false-negative
      findings on sonography (n = 19) showed microcalcifications on mammography. On
      sonography, masses were more frequently found in non-high-grade (62.5%) than high
      grade DCIS (22.7%; P < .01). No significant difference was seen in the
      sonographic features of masses between high-grade and non-high-grade DCIS.
      Microcalcifications were more common in high-grade (43.2%) than non-high-grade
      (3.1%) DCIS (P = .02). Most sonographically visible microcalcifications had
      associated findings such as ductal changes (n = 11), a mass (n = 7), or a
      hypoechoic area (n = 5). The detection rate of microcalcifications on sonography
      was higher in high-grade (62.9%) than non-high-grade DCIS (25.0%; P = .023).
      CONCLUSIONS: Microcalcifications with associated ductal changes (11 of 31
      [35.5%]) were the most common sonographic findings in high-grade DCIS. An
      irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26
      [50.0%]) was the most frequent finding in non-high-grade DCIS.

PMID- 21098840
TI  - Dynamic visualization of lymphatic channels and sentinel lymph nodes using
      intradermal microbubbles and contrast-enhanced ultrasound in a swine model and
      patients with breast cancer.
AB  - OBJECTIVE: Sentinel lymph node (SLN) identification using intradermal micro
      bubbles and contrast-enhanced ultrasound (CEUS) has been recently reported in
      swine models and patients with breast cancer. The objective of this study was to
      investigate the dynamics of intradermally administered microbubbles as they
      travel to draining SLNs in pigs. We also performed a detailed study of the
      passage of microbubbles through breast lymphatic channels in a small group of
      patients with breast cancer. METHODS: Nine anesthetized healthy pigs were used
      for the study, and 5 female patients with primary breast cancer were recruited.
      Pigs received intradermal injections of a microbubble contrast agent in several
      territories to access lymphatic drainage to regional lymph nodes. Patients had
      periareolar intradermal injection of the microbubble contrast agent. Ultrasound
      examination was performed in the real-time contrast pulse sequencing mode with a
      commercial scanner. RESULTS: Sentinel lymph nodes were identified rapidly (<1
      minute) and consistently in pigs. Intradermal microbubble injection and CEUS were
      found to have perfect concordance with the Evans blue dye method in locating
      swine SLNs. In all 5 patients with breast cancer, the microbubble contrast agent
      entered breast lymphatic channels and traveled to draining ipsilateral axillary
      SLNs within 3 minutes. CONCLUSIONS: Intradermally injected microbubbles traverse
      readily though lymphatic channels in pigs and human breast tissue. The ability to
      rapidly identify SLNs in the diagnostic period would enable targeted biopsy and
      may facilitate preoperative axillary staging in patients with early breast
      cancer.

PMID- 21098841
TI  - Predictive value of sonographic features of extranodal extension in axillary
      lymph nodes.
AB  - OBJECTIVE: The purpose of this study was to assess the accuracy of 5 sonographic
      features in the prediction of extranodal extension (ENE) in axillary lymph nodes
      (ALNs) of patients with biopsy-proven breast cancer. METHODS: A review of our
      institution's surgical and pathologic database was performed for patients with
      pathologically proven axillary ENE from October 1, 2003, to October 1, 2007. An
      equivalent number of patients without ENE were included. All patients had
      sonograms of ALNs available. A radiologist to whom the study was masked reviewed
      ALN images with specific attention to unclear margins, node matting, perinodal
      edema, and hilar effacement or replacement. Univariate and multivariate logistic
      regression analyses were used to obtain the sensitivity, specificity, and odds
      ratio (OR) for each feature. RESULTS: Our review included a total of 131 patients
      (64 with ENE and 67 without ENE). The respective sensitivity and specificity
      estimates for each feature were as follows: node matting, 52% and 84%; perinodal
      edema, 34% and 87%; unclear margins, 64% and 75%; hilar replacement, 71% and 42%;
      and hilar effacement, 74% and 60%. Univariate analysis showed a statistically
      significant association between features and ENE with ORs as follows: matting,
      5.4; perinodal edema, 3.4; unclear margins, 5.2; and hilar replacement, 4.3.
      Multivariate analysis showed that matting and unclear margins were independently
      associated with ENE. CONCLUSIONS: The sonographic features of unclear margins,
      node matting, perinodal edema, and hilar replacement have a statistically
      significant association with ENE. The sonographic features of unclear margins,
      node matting, and perinodal edema predict ENE with high specificity.

PMID- 21098842
TI  - Sonographic findings of acute vasitis.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic findings of
      acute vasitis. METHODS: This was a retrospective analysis of 12 cases of acute
      vasitis. The following gray scale and color Doppler sonographic features were
      analyzed: location, echogenicity of the lesion, presence of hydrocele, epididymal
      involvement, and blood flow within the lesion. RESULTS: Of the 12 patients, 10
      had acute vasitis in the scrotal segment; 1 had acute vasitis in the suprascrotal
      segment; and 1 had acute vasitis in both the scrotal and suprascrotal segments.
      The sonographic finding for acute vasitis of the scrotal segment was a
      heterogeneously hypoechoic appearance of the vas deferens (n = 11). The vas
      deferens was thickened (6.4 mm in diameter) in the 2 patients with suprascrotal
      involvement; it was heterogeneously hypoechoic in 1 and had a normal appearance
      in the other. On color Doppler sonography, the degree of blood flow was increased
      in all of the cases. Of the 12 patients, 11 had inflammation of the epididymis.
      CONCLUSIONS: Acute vasitis usually presents with infection combined with acute
      epididymitis, and it usually appears as a heterogeneously hypoechoic lesion in
      the scrotal segment, suprascrotal segment, or both.

PMID- 21098843
TI  - Sonographic findings for the common extensor tendon of the elbow in the general
      population.
AB  - OBJECTIVE: To describe structural characteristics and sonographic alterations of
      the common extensor tendon (CET). METHODS: In 240 patients, we determined the
      body mass index; sonographic CET thickness, morphologic characteristics, and
      alterations; and color Doppler measurements of the epicondylar artery width and
      peak systolic velocity. Age, sex, epicondylalgia history, activities (work,
      sports, and hobbies), and dominant and nondominant elbows were noted. RESULTS:
      The CET was thicker in the dominant elbow (4.77 versus 4.61 mm [P = .023]), male
      patients (dominant, 5.09 versus 4.46 mm [P < .001]; nondominant, 5.00 versus 4.21
      mm [P < .001]), patients involved in risk activities (dominant, 5.21 versus 4.70
      mm [P < .001]; nondominant, 5.12 versus 4.53 mm [P < .001]), and those with a
      history of epicondylalgia (right, 5.27 versus 4.70 mm [P < .001]; left, 4.86
      versus 4.60 mm [P = .316]). Thickness correlated weakly with age (dominant, r =
      0.284; nondominant, r = 0.215) and moderately with weight (dominant, r = 0.492;
      nondominant, r = 0.502). The mean epicondylar artery diameter was 1.35 mm (SD,
      0.96 mm); mean peak velocity, 13.01 cm/s (SD, 4.90 cm/s). Morphologic
      abnormalities were found in 79.5% of patients with a history of epicondylalgia;
      7.7% with no history had abnormalities; and 55.9% with abnormalities but no
      history were older than 55 years. Bone spurs (49.2% versus 16.4% [P < .001]),
      tendon calcifications (21.5% versus 3.9% [P < .001]), and bone cortex
      abnormalities (12.3% versus 1.7% [P < .001]) were found more often in non-normal
      elbows; 79.4% of bone spurs in normal elbows occurred in patients older than 55
      years. CONCLUSIONS: Mild sonographic alterations in the CET and bone spurs should
      be considered with caution when assessing epicondylar pain, especially in
      patients older than 55 years and those with a history of epicondylalgia.

PMID- 21098844
TI  - Comparison between exclusively long-axis and multiple-axis sonographic protocols
      for screening of rotator cuff lesions in symptomatic shoulders.
AB  - OBJECTIVE: The purpose of this study was to determine whether exclusively long
      axis sonography differs from a multiple-axis scanning protocol as a screening
      tool for rotator cuff lesions in symptomatic shoulders when compared with
      magnetic resonance imaging (MRI). METHODS: A total of 509 consecutive patients
      (mean age, 52.8 years) referred for MRI were also routinely evaluated by
      sonography. We initially performed exclusively long-axis sonography and graded
      the rotator cuff as normal or abnormal. Patients subsequently underwent a full
      sonographic protocol using multiple-axis views. Magnetic resonance imaging
      findings were compared with sonographic findings for both techniques. RESULTS:
      The overall accuracy of sonography was greater than 90%. We found divergent
      results from different sonographic techniques in 34 patients. Of these, 8 were
      multiple-axis false-negative; 14 were exclusively long-axis false-negative; 6
      were exclusively long-axis false-positive; and 6 were multiple-axis false
      positive. All cases with divergent false-negative findings on multiple-axis
      sonography showed tendinosis on MRI. Causes for false-negative findings on
      exclusively long-axis sonography included tendinosis and partial-thickness tears
      of the supraspinatus. No statistically significant difference was seen between
      both sonographic techniques compared with MRI in terms of accuracy, sensitivity,
      specificity, positive predictive value, and negative predictive value (P > .05).
      CONCLUSIONS: Sonography is reliable for detecting rotator cuff abnormalities.
      Exclusively long-axis sonography seems appropriate as a screening tool for
      rotator cuff lesions in symptomatic shoulders.

PMID- 21098845
TI  - Association between second-trimester cervical length and spontaneous preterm
      birth in twin pregnancies.
AB  - OBJECTIVE: The purpose of this study was to define normal second-trimester
      cervical length (CL) measurements and to estimate the association between second
      trimester CL and spontaneous preterm birth (SPTB) in twin pregnancies. METHODS: A
      retrospective cohort of 309 asymptomatic patients with twin pregnancies who had
      routine outpatient CL assessment in the second trimester was studied. We looked
      at the gestational age periods of 16 to 17 6/7, 18 to 19 6/7, 20 to 21 6/7, and
      22 to 23 6/7 weeks. We estimated the association between the CL measurement
      during each period and SPTB. A short CL was defined both as a CL at or below the
      10th percentile for gestational age and 25 mm or less. We also performed
      regression analyses controlling for a number of clinically important factors:
      maternal age, chorionicity, in vitro fertilization, multifetal reduction, prior
      term births, prior preterm births, prepregnancy body mass index, and cerclage.
      RESULTS: The CL measurement at 16 to 17 6/7 weeks was not associated with
      gestational age at delivery or SPTB. At 18 to 19 6/7 and 20 to 21 6/7 weeks, the
      CL measurement was not significantly associated with gestational age at delivery
      or SPTB before 28 and 32 weeks. There was an association with SPTB before 35
      weeks. At 22 to 23 6/7 weeks, the CL measurement had a significant association
      with gestational age at delivery and SPTB before 28, 32, and 35 weeks (P < .05).
      A short CL at 22 to 23 6/7 weeks was significantly associated with SPTB before 32
      and 35 weeks (P < .05). CONCLUSIONS: In second-trimester twin pregnancies, the
      strongest association between CL and SPTB is at 22 to 23 6/7 weeks.

PMID- 21098846
TI  - Model-predicted performance of second-trimester Down syndrome screening with
      sonographic prenasal thickness.
AB  - OBJECTIVE: The purpose of this study was to estimate the Down syndrome detection
      and false-positive rates for second-trimester sonographic prenasal thickness (PT)
      measurement alone and in combination with other markers. METHODS: Multivariate
      log Gaussian modeling was performed using numerical integration. Parameters for
      the PT distribution, in multiples of the normal gestation-specific median (MoM),
      were derived from 105 Down syndrome and 1385 unaffected pregnancies scanned at 14
      to 27 weeks. The data included a new series of 25 cases and 535 controls combined
      with 4 previously published series. The means were estimated by the median and
      the SDs by the 10th to 90th range divided by 2.563. Parameters for other markers
      were obtained from the literature. RESULTS: A log Gaussian model fitted the
      distribution of PT values well in Down syndrome and unaffected pregnancies. The
      distribution parameters were as follows: Down syndrome, mean, 1.334 MoM; log(10)
      SD, 0.0772; unaffected pregnancies, 0.995 and 0.0752, respectively. The model
      predicted detection rates for 1%, 3%, and 5% false-positive rates for PT alone
      were 35%, 51%, and 60%, respectively. The addition of PT to a 4-serum marker
      protocol increased detection by 14% to 18% compared with serum alone. The
      simultaneous sonographic measurement of PT and nasal bone length increased
      detection by 19% to 26%, and with a third sonographic marker, nuchal skin fold,
      performance was comparable with first-trimester protocols. CONCLUSIONS: Second
      trimester screening with sonographic PT and serum markers is predicted to have a
      high detection rate, and further sonographic markers could perform comparably
      with first-trimester screening protocols.

PMID- 21098847
TI  - Sonography in the evaluation of acute appendicitis: are negative sonographic
      findings good enough?
AB  - OBJECTIVE: The purpose of this study was to evaluate the negative predictive
      value (NPV) of sonography in the diagnosis of acute appendicitis. METHODS: Right
      lower quadrant sonograms of 193 patients (158 female and 35 male; age range, 3-20
      years) with suspected acute appendicitis over a 1-year period were
      retrospectively reviewed. Sonographic findings were graded on a 5-point scale,
      ranging from a normal appendix identified (grade 1) to frankly acute appendicitis
      (grade 5). Sonographic findings were compared with subsequent computed
      tomographic (CT), surgical, and pathologic findings. The diagnostic accuracy of
      sonography was assessed considering surgical findings and clinical follow-up as
      reference standards. RESULTS: Forty-nine patients (25.4%) had appendicitis on
      sonography, and 144 (74.6%) had negative sonographic findings. Computed
      tomographic scans were obtained in 51 patients (26.4%) within 4 days after
      sonography. These included 39 patients with negative and 12 with positive
      sonographic findings. Computed tomography changed the sonographic diagnosis in 10
      patients: from negative to positive in 3 cases and positive to negative in 7.
      Forty-three patients (22.2%) underwent surgery. The surgical findings were
      positive for appendicitis in 37 (86%) of the 43 patients who had surgery.
      Patients with negative sonographic findings who, to our knowledge, did not have
      subsequent CT scans or surgery were considered to have negative findings for
      appendicitis. Seven patients with negative sonographic findings underwent surgery
      and had appendicitis; therefore, 137 of 144 patients with negative sonographic
      findings did not have appendicitis. On the basis of these numbers, the NPV was
      95.1%. CONCLUSIONS: Sonography has a high NPV and should be considered as a
      reasonable screening tool in the evaluation of acute appendicitis. Further
      imaging could be performed if clinical signs and symptoms worsen.

PMID- 21098849
TI  - Effects of heart rate and anesthetic timing on high-resolution echocardiographic
      assessment under isoflurane anesthesia in mice.
AB  - OBJECTIVE: Anesthesia provides sedation and immobility, facilitating
      echocardiography in mice, but it influences cardiovascular function and therefore
      outcomes of measurement. This study aimed to determine the effect of the optimal
      heart rate (HR) and anesthetic timing on echocardiographic reproducibility under
      isoflurane anesthesia. METHODS: Male C57BL/6J mice underwent high-resolution
      echocardiography with relative fixed HRs and anesthetic timing. The same
      experiment was repeated once again after 1 week. RESULTS: Echocardiography was
      highly reproducible in repeated measurements under low-HR (350-400 beats per
      minute [bpm]) and high-HR (475-525 bpm) conditions except some M-mode parameters
      under low-HR conditions. With similar anesthetic timing, mice with a high HR had
      decreased preload indices and increased ejection phase and Doppler indices.
      Inversely, when the HR was similar, the echocardiographic results of mice under
      short anesthetic timing showed little difference from the ones under long
      anesthetic timing. CONCLUSIONS: This study shows that echocardiographic
      assessment is greatly reproducible under a high HR. The HR is more important than
      anesthetic timing for echocardiographic evaluation in mice.

PMID- 21098848
TI  - Associations of carotid artery intima-media thickness (IMT) with risk factors and
      prevalent cardiovascular disease: comparison of mean common carotid artery IMT
      with maximum internal carotid artery IMT.
AB  - OBJECTIVE: The goal of this study was to compare internal carotid artery (ICA)
      intima-media thickness (IMT) with common carotid artery (CCA) IMT as global
      markers of cardiovascular disease (CVD). METHODS: Cross-sectional measurements of
      the mean CCA IMT and maximum ICA IMT were made on ultrasound images acquired from
      the Framingham Offspring cohort (n = 3316; mean age, 58 years; 52.7% women).
      Linear regression models were used to study the associations of the Framingham
      risk factors with CCA and ICA IMT. Multivariate logistic regression models and
      receiver operating characteristic (ROC) curve analysis were used to compare the
      associations of prevalent CVD with CCA and ICA IMT and determine sensitivity and
      specificity. RESULTS: The association between age and the mean CCA IMT
      corresponded to an increase of 0.007 mm/y; the increase was 0.037 mm/y for the
      ICA IMT. Framingham risk factors accounted for 28.6% and 27.5% of the variability
      in the CCA and ICA IMT, respectively. Age and gender contributed 23.5% to the
      variability of the CCA IMT and 22.5% to that of the ICA IMT, with the next most
      important factor being systolic blood pressure (1.9%) for the CCA IMT and smoking
      (1.6%) for the ICA IMT. The CCA IMT and ICA IMT were statistically significant
      predictors of prevalent CVD, with the ICA IMT having a larger area under the ROC
      curve (0.756 versus 0.695). CONCLUSIONS: Associations of risk factors with CCA
      and ICA IMT are slightly different, and both are independently associated with
      prevalent CVD. Their value for predicting incident cardiovascular events needs to
      be compared in outcome studies.

PMID- 21098850
TI  - The stripe artifact in transcranial ultrasound imaging.
AB  - OBJECTIVE: Transcranial images are affected by a "stripe artifact" (also known as
      a "streak artifact"): two dark stripes stem radially from the apex to the base of
      the scan. The stripes limit the effective field of view even on patients with
      good temporal windows. This study investigated the angle dependency of ultrasound
      transmission through the skull to elucidate this artifact. METHODS: In vivo
      transcranial images were obtained to illustrate the artifact. In vitro hydrophone
      measurements were performed in water to evaluate transcranial wavefronts at
      different incidence angles of the ultrasound beam. Both a thin acrylic plate, as
      a simple bone model, and a human temporal bone sample were used. RESULTS: The
      imaging wavefront splits into two after crossing the solid layer (acrylic model
      or skull sample) at an oblique angle. An early-arrival wavefront originates from
      the direct longitudinal wave transmission through water-bone interfaces, while a
      late-arrival wavefront results from longitudinal-to-transverse mode conversion at
      the water-bone interface, propagation of the transverse wave through the skull,
      and transverse-to-longitudinal conversion at the bone-water interface. At normal
      incidence, only the direct wavefront (without mode conversion) is observed. As
      the incidence angle increases, the additional "mode conversion" wavefront
      appears. The amplitude of the transcranial wavefront decreases and reaches a
      minimum at an incidence angle of about 27 degrees . Beyond that critical angle,
      only the mode conversion wavefront is transmitted. CONCLUSIONS: The stripes are a
      consequence of the angle-dependent ultrasound transmission and mode conversion at
      fluid-solid interfaces such as between the skull and the surrounding fluidlike
      soft tissues.

PMID- 21098851
TI  - Correlations between B-mode ultrasonic image texture features and tissue
      temperature in microwave ablation.
AB  - OBJECTIVE: The purpose of this study was to find the correlations between B-mode
      ultrasonic tissue texture features and tissue temperature in microwave ablation.
      METHODS: A total of 20 in vitro porcine liver samples were used for microwave
      ablation experiments. B-mode ultrasonic images under various temperatures were
      acquired. The texture features of the differential images based on the gray level
      histogram, including the mean of the gray scale (MGS), standard deviation of the
      gray scale, and entropy of the gray scale (ENT), and those based on the gray
      level co-occurrence matrix, including the contrast (CON), angular second moment
      (ASM), inverse difference moment (IDM), and correlation, were extracted.
      Correlations between the features and liver sample temperature were analyzed. In
      addition, water bath heating experiments were also performed on 15 in vitro
      porcine liver samples for analysis validation. RESULTS: The correlation
      coefficients across the MGS, ENT, and ASM in 4 directions (0 degrees , 45 degrees
      , 90 degrees , and 135 degrees ), the CON and IDM in 3 directions (45 degrees ,
      90 degrees , and 135 degrees ), and a temperature range of 15 degrees C to 90
      degrees C were high and greater than 0.9 during microwave ablation. All texture
      features of the differential B-mode ultrasonic images changed with rising
      temperature from 25 degrees C to 60 degrees C during water bath heating.
      CONCLUSIONS: Changes in image features reflect changes in tissue temperature
      during microwave ablation.

PMID- 21098852
TI  - Comparison of reproducibility of manual and sphere contour methods for the
      measurement of vascularization in cervical carcinoma using the virtual organ
      computer-aided analysis II system.
AB  - OBJECTIVE: The purpose of this study was to investigate the reproducibility of
      virtual organ computer-aided analysis II software (GE Healthcare, Milwaukee, WI),
      an integrated tool for 3-dimensional power Doppler angiography (3D-PDA), in
      measuring vascularization of cervical carcinoma under manual and automatic sphere
      contour modes. METHODS: Eighty patients with cervical carcinoma were
      prospectively examined by observer 1 using transvaginal 3D-PDA. For each patient,
      measurements of the vascularization index, flow index, and vascularization-flow
      index were repeated twice under both manual and automatic sphere contour modes.
      Forty patients were randomly selected for another round of examination by
      observer 2 under the same setting. The reproducibility of vascularization
      measurements was assessed by the intraclass correlation coefficient (intra-CC),
      interclass correlation coefficient (inter-CC), and 95% limits of agreement
      (LOAs). Various analysis of variance models were used to estimate the
      contribution of each factor (observer, contour mode, and patient) to measurement
      variance. RESULTS: For each observer, the manual contour mode outperformed the
      automatic sphere contour mode in reproducibility (intra-CC, 0.96 to 0.99 versus
      0.77 to 0.94). In addition, repeated measurements of the manual mode had a
      smaller SD and a narrower LOA. For the manual contour mode, interobserver
      agreement was comparable with intraobserver agreement (inter-CC, 0.91 to 0.98,
      versus intra-CC, 0.96 to 0.99). However, the interobserver agreement was
      significantly smaller than the intraobserver agreement for the automatic sphere
      contour mode (inter-CC, 0.51 to 0.85, versus intra-CC, 0.77 to 0.94; P = .001).
      CONCLUSIONS: The manual contour mode for 3D-PDA vascular measurements has better
      interobserver and intraobserver reproducibility than the automatic sphere contour
      mode. It is especially useful for measuring tumor tissues with irregular shapes
      and vascularity.

PMID- 21098853
TI  - Extracranial and intracranial sonographic findings in vertebral artery diseases.
AB  - OBJECTIVE: The aim of this review is to illustrate the sonographic features that
      can be detected in vertebral artery (VA) diseases. METHODS: We conducted a review
      of sonographic findings in VA diseases. RESULTS: Various VA diseases are
      described, and sonographic techniques and features are discussed. CONCLUSIONS:
      Posterior circulation vascular imaging can be performed by means of various
      neuroimaging techniques. Intra-arterial angiography remains the reference
      standard. The use of this technique has become even more widespread since it has
      become possible to perform endovascular procedures; it is, however, an invasive
      procedure that is associated with a not irrelevant level of risk. Computed
      tomographic angiography and magnetic resonance angiography with and without
      contrast agents have been proposed as less invasive alternatives, although these
      techniques can only be performed in the radiology unit and may not be readily
      available in daily clinical management. Sonography, which combines an
      extracranial and intracranial evaluation, is highly suited to the assessment of
      the vertebrobasilar system on account of its widespread availability and its
      unique capacity to study real-time hemodynamics. Furthermore, new sonographic
      applications and sonographic contrast agents have improved the sensitivity and
      specificity of this technique with regard to diagnostic accuracy for the
      posterior circulation.

PMID- 21098854
TI  - Diagnosis of pentalogy of Cantrell using 2- and 3-dimensional sonography.

PMID- 21098855
TI  - Bilateral interstitial pregnancy after in vitro fertilization and embryo transfer
      with bilateral fallopian tube resection detected by transvaginal sonography.

PMID- 21098856
TI  - Myofibroblastoma of the female breast: mammographic, sonographic, and magnetic
      resonance imaging findings.

PMID- 21098857
TI  - Retroperitoneal lymphangioleiomyomatosis: sonography, computed tomography,
      magnetic resonance imaging, and positron emission tomography with pathologic
      correlation.

PMID- 21098858
TI  - Retroperitoneal extragonadal endodermal sinus tumor with bilateral diffuse
      classic testicular microlithiasis.

PMID- 21098859
TI  - Sonographic evaluation of enchondroma with soft tissue extension in the setting
      of Ollier disease.

PMID- 21098860
TI  - Humanins, the neuroprotective and cytoprotective peptides with antiapoptotic and
      anti-inflammatory properties.
AB  - Humanin (HN) is a newly discovered 24-amino acid peptide, which may suppress
      neuronal cell death. HN cDNA includes an open reading frame (HN-ORF) of 75 bases
      located 950 bases downstream of the 5' end of the HN cDNA. It has been
      demonstrated that HN cDNA is 99% identical to the mitochondrial DNA (mtDNA)
      sequence. HN homologs have been identified as expressed sequence tags (ESTs) in
      both rats and nematodes. Certain regions that are homologous to the HN cDNA exist
      on human chromosomes. HN forms homodimers and multimers and this action seems to
      be essential for peptide function. HN acts as a ligand for formyl peptide
      receptor-like 1 (FPRL1) and 2 (FPRL2). It has been demonstrated that HN plays a
      protective role through its antiapoptotic activity that interferes with Bax
      activation, which suppresses Bax-dependent apoptosis. HN has also been shown to
      suppress the c-Jun N-terminal kinase (JNK) and ASK/JNK-mediated neuronal cell
      death. Several studies have also confirmed that HN could be important in the
      prevention of angiopathy-associated Alzheimer's disease dementia, diseases
      related to mitochondrial dysfunction (MELAS), and other types of beta-amyloid
      accumulation-associated neurodegeneration. Avery recent study demonstrated a
      pluripotent cytoprotective effect and mechanisms of HNs in cells not from the
      CNS, such as germ cells or pancreatic beta-cells, and the potent physiological
      consequences that result from HN interaction with IGFBP3 and STAT3. In vivo
      studies suggest that HN may also protect against cognitive impairment due to
      ischemia/reperfusion injury.

PMID- 21098861
TI  - Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB): a new
      potential therapeutic target in atherosclerosis?
AB  - Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) is a
      crucial transcription factor that participates in a number of physiological and
      pathological conditions, including immune response, apoptosis, carcinogenesis and
      inflammatory processes. It is involved in the rapid response to various stimuli
      such as viral and bacterial infections, shear stress, oxidant stress and a number
      of cytokines. In the pathology of atherosclerosis NF-kappaB is essential to the
      cross-talk between cytokines, adhesion molecules and growth factors, leading to
      atherosclerotic plaque formation, growth and eventual rupture. The intent of this
      paper is to gather and summarize information on the role of NF-kappaB in the
      pathology of atherosclerosis. Additionally, pharmacological intervention in the
      signaling of NF-kappaB is addressed along with the potential benefits and
      disadvantages of NF-kappaB modulating treatment.

PMID- 21098862
TI  - Memory restorative role of statins in experimental dementia: an evidence of their
      cholesterol dependent and independent actions.
AB  - The study was aimed at investigating the effects of pitavastatin, simvastatin
      (lipophilic statins) and fluvastatin (hydrophilic statin) on memory deficits
      associated with Alzheimer's type dementia in mice. Dementia was induced with
      chronic administration of a high fat diet (HFD) or intracebroventricular
      streptozotocin (icv STZ, two doses of 3 mg/kg) in separate groups of animals.
      Memory of the animals was assessed by the Morris water maze (MWM) test. Brain
      thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels
      were measured to assess total oxidative stress. Brain acetylcholinesterase (AChE)
      activity and total serum cholesterol levels were also measured. Icv STZ or HFD
      produced a significant impairment of learning and memory. Higher levels of brain
      AChE activity and TBARS and lower levels of GSH were observed in icv STZ- as well
      as HFD-treated animals. HFD-treated mice also showed a significant increase in
      total serum cholesterol levels. Pitavastatin and simvastatin each significantly
      attenuated STZ-induced memory deficits and biochemical changes; however,
      fluvastatin produced no significant effect on icv STZ-induced dementia or
      biochemical levels. Administration of any one of the three statins not only
      lowered HFD-induced rise in total serum cholesterol level but also attenuated HFD
      induced memory deficits. Further pitavastatin and simvastatin administration also
      reversed HFD-induced changes in biochemicals level, while fluvastatin failed to
      produce any significant effect. This study demonstrates the potential of statins
      in memory dysfunctions associated with experimental dementia and provides
      evidence of their cholesterol-dependent and -independent actions.

PMID- 21098863
TI  - Rimonabant attenuates sensitization, cross-sensitization and cross-reinstatement
      of place preference induced by nicotine and ethanol.
AB  - The present study focused on the evaluation of behavioral sensitization, cross
      sensitization, and cross-reinstatement processes induced by nicotine and ethanol
      in rodents. First, we showed that nicotine (0.175 mg/kg, base, intraperitoneally,
      ip) produced a conditioned place preference in rats. When the nicotine place
      preference was extinguished, nicotine-experienced animals were challenged with
      nicotine (0.175 mg/kg, ip) or ethanol (0.5 g/kg, ip), which reinstated a
      preference for the compartment previously paired with nicotine. In the second
      series of experiments, we demonstrated that after 9 days of nicotine
      administration (0.175 mg/kg, subcutaneously, sc) every other day and following
      its 7-day withdrawal, challenge doses of nicotine (0.175 mg/kg, sc) and ethanol
      (2 g/kg, ip) induced locomotor sensitization in mice. Finally, when we examined
      the influence of rimonabant (0.5, 1 and 2 mg/kg, ip), we found that this
      cannabinoid CB1 receptor antagonist attenuated reinstatement effect of ethanol
      priming as well as nicotine sensitization and locomotor cross-sensitization
      between nicotine and ethanol. Our results indicate that similar endocannabinoid
      dependent mechanisms re involved in the locomotor stimulant and reinforcing
      effects of nicotine and ethanol in rodents, and as such these data may provide
      further evidence for the use of cannabinoid CB1 receptor antagonists in treatment
      of tobacco addiction with or without concomitant ethanol dependence.

PMID- 21098864
TI  - Influence of ethacrynic acid on the anticonvulsant activity of conventional
      antiepileptic drugs in the mouse maximal electroshock seizure model.
AB  - The aim of this study was to determine whether ethacrynic acid (EA), a loop
      diuretic with anticonvulsant activity, would affect the protective action of the
      conventional antiepileptics (AEDs) carbamazepine (CBZ), phenytoin (PHT),
      valproate (VPA) and phenobarbital (PB) in the mouse maximal electroshock seizure
      (MES) model. The effects of acute and chronic treatment with EA on these AEDs
      were examined. At a single dose of 100 mg/kg ip, EA enhanced the antielectroshock
      activity of VPA, decreasing its ED50 value from 225.6 to 146.6 mg/kg (p < 0.05),
      but enhancement was not observed following continuous administration of EA (12.5
      mg/kg) for seven days. Combined treatment of EA with other AEDs had no effect on
      their ED50 values. The observed interaction between EA and VPA was
      pharmacodynamic in nature as EA did not alter free plasma (non-protein-bound) and
      total brain concentrations of VPA. Taking into consideration the clinical use of
      both drugs, this interaction between EA and VPA can be important for patients
      receiving these drugs.

PMID- 21098865
TI  - Cytosolic phospholipase A2 inhibition is involved in the protective effect of
      nortriptyline in primary astrocyte cultures exposed to combined oxygen-glucose
      deprivation.
AB  - The protective potential of nortriptyline has been reported in a few experimental
      models of brain ischemia, both in vivo and in vitro. However, the detailed
      molecular mechanisms of the protective action of the drug are still unresolved.
      The aim of the present study was to determine whether treatment with low or
      medium concentrations of nortriptyline (0.1-10 MUM) might have an effect on cPLA2
      protein and/or mRNA expression in ischemic astrocytes, and whether this influence
      might be related to its potential positive influence on cell viability. On the
      21(st) day in vitro, primary cultures of rat cortical astrocytes were subjected
      to ischemia-simulating conditions (combined oxygen glucose deprivation, OGD) for
      24 h and exposed to nortriptyline. The drug at concentrations of 0.1 and 1 MUM
      attenuated the expression of cPLA2 (both the phosphorylated and unphosphorylated
      forms) together with a significant decrease in the cPLA2 mRNA level in ischemic
      astrocytes. We have demonstrated that nortriptyline influences a decrease in
      cPLA2-mediated arachidonic acid (AA) release through a mechanism that appears to
      involve the attenuation of both PKC and Erk1/2 kinase expression. Nortriptyline
      also significantly prevented mitochondrial depolarization in ischemic astrocytes.
      Moreover, the antidepressant protected glial cells against OGD-induced apoptosis
      and necrosis. Our findings document a role for cPLA2 expression attenuation and
      AA release inhibition in the protective effect of nortriptyline in ischemic
      astrocytes.

PMID- 21098866
TI  - Metformin has adenosine-monophosphate activated protein kinase (AMPK)-independent
      effects on LPS-stimulated rat primary microglial cultures.
AB  - The results of recent studies suggest that metformin, in addition to its efficacy
      in treating type 2 diabetes, may also have therapeutic potential for the
      treatment of neuroinflammatory diseases in which reactive microglia play an
      essential role. However, the molecular mechanisms by which metformin exerts its
      anti-inflammatory effects remain largely unknown. Adenosine-monophosphate
      activated protein kinase (AMPK) activation is the most well-known mechanism of
      metformin action; however, some of the biological responses to metformin are not
      limited to AMPK activation but are mediated by AMPK-independent mechanisms. In
      this paper, we attempted to evaluate the effects of metformin on unstimulated and
      LPS-activated rat primary microglial cell cultures. The presented evidence
      supports the conclusion that metformin-activated AMPK participates in regulating
      the release of TNF-alpha. Furthermore, the effects of metformin on the release of
      IL-1beta, IL-6, IL-10, TGF-beta, NO, and ROS as well as on the expression of
      arginase I, iNOS, NF-kappaB p65 and PGC-1alpha were not AMPK-dependent, because
      pretreatment of LPS-activated microglia with compound C, a pharmacological
      inhibitor of AMPK, did not reverse the effect of metformin. Based on the present
      findings, we propose that the shift of microglia toward alternative activation
      may underlie the beneficial effects of metformin observed in animal models of
      neurological disorders.

PMID- 21098867
TI  - New antinociceptive agents related to dihydrosphingosine.
AB  - The main objective of this study was to evaluate the antinociceptive activity of
      three ethylenediamine derivatives and three beta-aminoethanol lipidic derivatives
      structurally related to dihydrosphingosine. These derivatives were selected on
      the basis of previous results from in vitro and in vivo anti-inflammatory
      studies. For all of the assayed compounds, an intraperitoneal dose of 3 mg/kg
      caused pronounced pain inhibition as measured by the acetic acid-induced writhing
      model in mice. Compounds 3 and 6 demonstrated strong antinociceptive activity at
      doses as low as 1 mg/kg and proved to be considerably more potent than the common
      nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) and
      acetaminophen (ACE). We further analyzed these compounds using the capsaicin- and
      glutamate-induced pain tests. Compounds 3 and 6 also exhibited considerable
      antinociceptive effects under these conditions, but their inhibitory effects in
      the formalin test were less pronounced. The exact mechanism of action for these
      compounds has yet to be established. However, based the results from a hot-plate
      test, it can be stated that these new drugs do not interact with the opioid
      system.

PMID- 21098868
TI  - Effects of subcutaneous and intracerebroventricular injection of physostigmine on
      the acute corneal nociception in rats.
AB  - The present study investigated the effects of subcutaneous (sc) and
      intracerebroventricular (icv) injections of physostigmine (a cholinesterase
      inhibitor), atropine (an antagonist of muscarinic cholinergic receptors) and
      hexamethonium (an antagonist of nicotinic cholinergic receptors) on the acute
      corneal nociception in rats. Local application of 5 M NaCl solution on the
      corneal surface of the eye produced a significant nociceptive behavior,
      characterized by eye wiping. The number of eye wipes was counted during the first
      30 s. The sc (0.25, 0.5 and 1 mg/kg) and icv (1.25, 2.5, 5 and 10 MUg) injections
      of physostigmine significantly (p < 0.05) decreased the number of eye wipes.
      Atropine and hexamethonium at (2 mg/kg, sc and 20 MUg, icv) had no effects when
      used alone, however, atropine, but not hexamethonium prevented the
      antinociception induced by physostigmine (sc and icv). The results of this study
      indicate that the central muscarinic, but not nicotinic receptors might be
      involved in the antinociceptive effect of physostigmine in the acute corneal
      model of pain in rats.

PMID- 21098869
TI  - Pinealectomy aggravates acute pancreatitis in the rat.
AB  - Melatonin, a pineal indoleamine, protects the pancreas against acute damage;
      however, the involvement of the pineal gland in the pancreatoprotective action of
      melatonin is unknown. The primary aim of this study was to determine the effects
      of pinealectomy on the course of acute caerulein-induced pancreatitis (AP) in
      rats. AP was induced by a subcutaneous infusion of caerulein (25 MUg/kg) into
      pinealectomized or sham-operated animals. Melatonin (5 or 25 mg/kg) was given via
      intraperitoneal (ip) injection 30 min prior to the induction of AP. The
      pancreatic content of the lipid peroxidation products malondialdehyde and 4
      hydroxynonenal (MDA + 4HNE) and the activity of an antioxidative enzyme,
      glutathione peroxidase (GSH-Px), were measured in each group of rats. Melatonin
      blood levels were measured by radioimmunoassay (RIA). In the sham-operated rats,
      AP was confirmed with histological examination and manifested as pancreatic edema
      and an increase in the blood lipase level (by 1,500%). In addition, the
      pancreatic content of MDA+ 4HNE was increased by 200%, and pancreatic glutathione
      peroxydase (GSH-Px) activity was reduced by 40%. Pinealectomy significantly
      aggravated the histological manifestations of AP, reduced the GSH-Px activity and
      markedly augmented the levels of MDA+ 4HNE in the pancreas of rats with or
      without AP as compared to sham-operated animals. Melatonin was undetectable in
      the blood of the pinealectomized rats with or without AP. Treatment with
      melatonin (25 mg/kg, ip) prevented the development of AP in the sham-operated
      rats and significantly reduced pancreatic inflammation in the animals previously
      subjected to pinealectomy. In conclusion, pineal melatonin contributes to the
      pancreatic protection through the activation of the antioxidative defense
      mechanism in pancreatic tissue as well as its direct antioxidant effects.

PMID- 21098870
TI  - Effect of clofibrate on vascular reactivity in a model of high blood pressure
      secondary to aortic coarctation.
AB  - The aims of this study were to identify the effect of clofibrate administration
      in the development of high blood pressure secondary to aortic coarctation (AoCo)
      and to assess its effect on vascular reactivity. Three experimental groups of
      rats were used: sham-operated, aortic coarctated vehicle-treated (AoCo-V), and
      aortic coarctated clofibrate-treated (AoCo-C100). The rats were treated for seven
      days. Blood pressure was measured, and the vascular response to angiotensin II
      (AngII), norepinephrine (NE), and acetylcholine (ACh) were evaluated in aortic
      rings. The activity and expression of endothelial nitric oxide synthase (eNOS)
      was also evaluated. The major findings of this study include the following: AoCo
      induced a rise in blood pressure, and this effect was attenuated by clofibrate.
      The vascular response to AngII was higher in aortic rings from the AoCo-V group
      compared to the Sham-V or AoCo-C100 groups. ACh-elicited vasorelaxation was lower
      in the arteries of AoCo-V rats than Sham-V or AoCo-C100, while it was comparable
      between the Sham-V and AoCo-C100 groups. In every case, vasorelaxation was
      dependent on NO. However, the ACh-induced release of NO as well as NOS activity
      and expression were reduced in the arteries of AoCo-V rats. Clofibrate maintained
      normal NOS activity and increased eNOS expression. In conclusion, clofibrate
      administration attenuated the AoCo-induced rise in blood pressure by a mechanism
      that involves the participation of the NO system at both the NO synthesis and the
      eNOS protein expression levels. These events improved endothelial function,
      preserved normal vascular responses to both vasorelaxants and vasoconstrictors,
      and led to better blood pressure control.

PMID- 21098871
TI  - Hypotensive effect of atorvastatin is not related to changes in inflammation and
      oxidative stress.
AB  - We sought to determine if atorvastatin lowers blood pressure in patients with
      previously diagnosed and well-controlled essential arterial hypertension and if
      this effect could be related to anti-inflammatory and anti-oxidative effects.
      Among 92 patients with essential arterial hypertension, we studied 56 non-smoking
      and normolipemic: 39 were randomized to receive 80 mg atorvastatin daily for 3
      months (statin-treated patients, ST), and the rest continued a previous
      hypotensive therapy (statin-free patients, SF). Blood pressure was measured using
      a 24-h ambulatory blood pressure measurement device. Serum levels of high
      sensitivity C-reactive protein (hs-CRP), total antioxidant status (TAS) and
      plasma peroxides (assessed by Oxystat) were measured in both groups. The mean
      change in systolic BP (SBP) for atorvastatin was -5.7 mmHg (95% confidence
      interval CI, -4.1 to -7.2 mmHg), and the mean change in diastolic BP (DBP) was 
      3.9 mmHg (95% CI, -2.7 to -5.0 mmHg). No change in BP in SF patients was
      observed. In the ST group, hs-CRP and peroxides did not significantly decrease.
      In the SF group, concentrations of hs-CRP proceeded to decrease while peroxides
      increased. In the ST group, changes in hs-CRP correlated with changes in total
      cholesterol and low-density lipoprotein cholesterol (r = 0.41, p = 0.013 and r =
      0.35, p = 0.04, respectively) but did not correlate with changes in BP. The
      hypotensive statin effect was independent of the hypolipemic effect. During three
      months of observation, TAS concentrations in both groups remained stable. In this
      randomized study, additionally administered atorvastatin to non-smoking and
      normolipemic patients with well-controlled essential arterial hypertension
      resulted in reduction of BP. This effect was not followed by significant changes
      in hs-CRP, TAS or Oxystat concentrations. The hypotensive effect of atorvastatin
      did not depend on anti-inflammatory, anti-oxidative or hypolipemic actions.

PMID- 21098872
TI  - Cigarette smoke-induced biochemical perturbations in human erythrocytes and
      attenuation by epigallocatechin-3-gallate--tea catechin.
AB  - The protective effect of epigallocatechin-3-gallate (EGCG) against cigarette
      smoke (CS) induced alterations in human erythrocyte was studied using an in vitro
      model. Hemolysis, carboxyhemoglobin, osmotic fragility, hemin, lipid peroxidation
      (LPO), protein thiol, protein carbonyl, glutathione, antioxidant enzymes,
      membrane bound ATPases and erythrocyte ghost protein were assessed to investigate
      the effect of EGCG. Erythrocytes were incubated with CS and/or 10 MUM EGCG under
      physiological conditions of temperature and pH for 2 h. CS significantly
      increased the percentage of hemolysis, carboxyhemoglobin, hemin, LPO and osmotic
      fragility in human erythrocytes whereas EGCG pretreatment significantly reduced
      all the above parameters. The levels of protein carbonyls significantly increased
      whereas the level of protein thiol decreased significantly in erythrocytes
      incubated with CS. EGCG pretreatment significantly decreased the levels of
      carbonyls and increased the level of protein thiol. The level of glutathione,
      antioxidant enzyme and membrane bound ATPases were decreased significantly in
      erythrocytes incubated with CS. However, EGCG pretreatment significantly
      increased the activities of GSH, antioxidant enzymes and membrane bound ATPases.
      CS incubated erythrocytes showed a progressive loss of the cytoskeleton proteins
      and formation of low molecular weight bands and protein aggregates. EGCG
      pretreatment of CS incubated erythrocytes showed a near normal protein profile
      compared to that of control erythrocytes. The present study divulges that EGCG
      can reduce the abnormalities of cigarette smoking by ameliorating the oxidative
      stress. This finding raises the possibility that EGCG may provide protection from
      CS induced toxicity.

PMID- 21098873
TI  - Effects of curcumin on the skeletal system in rats.
AB  - There is increasing interest in the discovery of natural compounds that could
      favorably affect the skeletal system. Curcumin is a constituent of turmeric, a
      plant which has been used for centuries as a dietary spice and a traditional
      Indian medicine. Curcumin has been reported to affect differentiation, activity
      and the lifespan of osteoblasts and osteoclasts in vitro. The aim of the present
      study was to investigate the effects of curcumin on the skeletal system of rats
      in vivo. Curcumin (10 mg/kg, po daily) was administered for four weeks to normal
      (non-ovariectomized) and bilaterally ovariectomized (estrogen-deficient) three
      month-old female Wistar Cmd:(WI)WU rats. Ovariectomy was performed seven days
      before the start of curcumin administration. Bone mass, mineral and calcium
      content, macrometric and histomorphometric parameters, as well as the mechanical
      properties of the bone, were examined. Serum total cholesterol and estradiol
      levels were also determined. In rats with normal estrogen levels, curcumin
      decreased serum estradiol level and slightly increased cancellous bone formation,
      along with decreased mineralization. Estrogen deficiency induced osteoporotic
      changes in the skeletal system of the ovariectomized control rats. In
      ovariectomized rats, curcumin decreased body mass gain and serum total
      cholesterol level, slightly improved some bone histomorphometric parameters
      impaired by estrogen deficiency, but did not improve bone mineralization or
      mechanical properties. In conclusion, the results of the present in vivo study in
      rats did not support the hypothesis that curcumin, at doses that are readily
      achievable through dietary intake, could be useful for the prevention or
      treatment of osteoporosis.

PMID- 21098874
TI  - Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin
      sensitized guinea pigs.
AB  - Different pharmacological effects from Nigella sativa have been demonstrated in
      guinea pig tracheal chains in previous studies. In the present study, the
      prophylactic effects of thymoquinone on lung pathology as well as blood IL-4 and
      IFN-gamma levels in sensitized guinea pigs were examined. Three groups of guinea
      pigs sensitized to ovalbumin were given drinking water alone (group S) or
      drinking water containing low (LTQ) or high (HTQ) concentrations of thymoquinone
      (groups S + LTQ and S + HTQ). The lung pathology as well as blood IL-4 and IFN
      gamma levels of the sensitized and the control guinea pigs were evaluated in
      three sensitized and one control group (n = 8, for all groups). The lungs of the
      S group showed significant pathological changes (p < 0.001). Blood IL-4 and IFN
      gamma levels were increased in the sensitized animals compared to those of
      controls (p < 0.01 and p < 0.001, respectively). Treatment of the S animals with
      thymoquinone significantly improved their pathological changes to the lung and
      decreased their IL-4 levels (p < 0.05 to p < 0.001) but increased their IFN-gamma
      levels (p < 0.001). These results showed a preventive effect of thymoquinone on
      lung inflammation in sensitized guinea pigs.

PMID- 21098877
TI  - Family-based study of brain-derived neurotrophic factor (BDNF) gene polymorphism
      in alcohol dependence.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to a family of proteins related
      to the nerve growth factor family, which are responsible for the proliferation,
      survival and differentiation of neurons. BDNF is thought to be involved in the
      pathogenesis of bipolar disorder, schizophrenia, eating disorders and addiction.
      We hypothesize that a functionally relevant polymorphism of the BDNF gene
      promoter may be associated with the pathogenesis of alcohol dependence. We
      performed an association study of 141 families with alcohol dependence. One
      hundred and thirty-eight healthy control subjects were matched based on ethnicity
      and gender. An association between the BDNF Val66Met gene polymorphism and
      alcoholism was not found.

PMID- 21098876
TI  - Effect of erythropoietin, 5-fluorouracil and SN-38 on the growth of DLD-1 cells.
AB  - Supplementation of recombinant human erythropoietin (rHuEpo) is one of the
      methods for the treatment of anemia. The influence of rHuEpo on proliferation or
      clonogenic growth of cancer cells is not clear and some of the published results
      are conflicting. The aim of this work was to study the effect of rHuEpo on colon
      cancer cells when given alone or in combination with cytostatics. Human colon
      adenocarcinoma cells (DLD-1) were cultured in medium with rHuEpo, 5-fluorouracil
      (5-FU) and an active metabolite of irinotecan (SN-38). Cell viability was
      determined using a hematocytometer and 0.4% (w/v) trypan blue dye. Cell
      proliferation was measured by the MTT assay. Expression of EpoR, Bax, Bcl-2 and
      Akt1 protein was assessed by Western blot. The results of this study indicate a
      dose-dependent inhibitory effect of rHuEpo on DLD-1 cell growth and
      proliferation. Moreover, the combined treatment of rHuEpo and cytotoxic agents
      such as 5-FU and SN-38 increases the antitumor action, which is indicated by
      decreases in proliferation in the MTT test, cell numbers and DNA synthesis. We
      found a significant increase in EpoR, Bcl-2 and Akt1 protein expression in all
      cells grown in medium containing 3 IU of rHuEpo. We observed that EpoR is
      constitutively expressed in DLD-1 cells. Our results indicate that rHuEpo acts
      via EpoR to directly inhibit DLD-1 cell growth and indirectly modulate the
      cytostatics effects of 5-FU and SN-38.

PMID- 21098875
TI  - Modulation of in vivo immunoglobulin production by endogenous histamine and H1R
      and H2R agonists and antagonists.
AB  - The present study was designed to delineate the immunomodulatory role of
      histamine receptors (H1R and H2R) and their antibody generation in a rabbit
      model. Six groups containing 18 rabbits each received either vehicle (sterile
      distilled water, 1 ml/kg x b.i.d), histamine (100 MUg/kg x b.i.d.), H1R agonist
      (HTMT, 10 MUg/kg x b.i.d.), H2R agonist (amthamine, 10 MUg/kg x b.i.d.), H1R
      antagonist (pheniramine, 10 mg/kg x b.i.d.) or H2R antagonist (ranitidine, 10
      mg/kg x b.i.d.). All animals were subsequently immunized with an intravenous
      injection of sheep red blood cells (SRBC). Estimations of total serum
      immunoglobulins (Igs), immunoglobulin M (IgM) and immunoglobulin G (IgG) were
      performed by ELISA and hemagglutination assay (HA) at days 0 (pre-immunization),
      7, 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed
      similar production of Igs, IgM and IgG but the results were found comparatively
      more significant by ELISA as opposed to HA. Results showed that histamine could
      influence a detectable antibody response to SRBC early (i.e., at day 7), which
      lasted until day 58. Immunomodulatory processes showed suppression of an Ig
      generation in the H1R-antagonist group with enhancement in the H2R-antagonist
      group. The H1R-agonist group showed an increased Ig production in comparison to
      the H2R-agonist group. The IgM production was inhibited in the H1R-antagonist
      group as compared to the H2R-antagonist group, and it was also suppressed in H1R
      agonist group as compared to H2R-agonist group. IgG production was inhibited in
      the H1R-antagonist group as opposed to the H2R-antagonist group. In contrast, the
      H1R-agonist group increased IgG production as compared to the H2R-agonist group.
      All the results were found to be statistically significant (p < 0.05 or p <
      0.01). In conclusion, histamine and its receptor (H1R and H2R) agonists enhance
      antibody production by triggering the histamine receptors (H1R and H2R), and both
      the H1R antagonist and the H2R antagonist positively or negatively regulate the
      antibody production. The findings of this study may have clinical significance.

PMID- 21098878
TI  - Dose-response relationship analysis of pregabalin doses and their antinociceptive
      effects in hot-plate test in mice.
AB  - The aim of this study was to determine the analgesic effects of pregabalin (a
      third-generation antiepileptic drug) using the acute thermal pain model (hot
      plate test) in mice. Linear regression analysis was used to evaluate a dose
      response relationship between logarithms of pregabalin doses and their resultant
      maximum possible antinociceptive effects (MPAE) using the hot-plate test in mice.
      From the linear equation of the dose-response relationship, doses of pregabalin
      that increased antinociceptive effects by 20%, 30%, 40%, and 50% were calculated
      and amounted to 9.33, 24.80, 65.93, and 175.26 mg/kg, respectively. In
      conclusion, pregabalin produces analgesic effects in a dose-dependent manner, as
      demonstrated using the hot-plate test in mice.

PMID- 21098879
TI  - Anti-apoptotic effects of hyperoside via inhibition of NR2B-containing NMDA
      receptors.
AB  - Hyperoside (Hyp) is a flavonoid compound isolated from a folk remedy,
      Rhododendron ponticum L. leaves. It has been shown to have neuroprotective
      effects both in vivo and in vitro. However, little is known about the effects of
      Hyp on the neuronal apoptosis induced by glutamate. The present study showed that
      Hyp significantly attenuated, in a concentration-dependent manner, the apoptosis
      induced by the exposure of cultured neurons to NMDA. Western blot analysis
      revealed that Hyp antagonized the expression of excess NR2B-containing NMDA
      receptors; however, it had no effect on the expression of NR2A-containing NMDA
      receptors. Our results demonstrate that the neuroprotective effect of Hyp owes,
      at least partially, to its differential modulation of NR2A- and NR2B-containing
      NMDA receptors.

PMID- 21098880
TI  - Quantification of metformin by the HPLC method in brain regions, cerebrospinal
      fluid and plasma of rats treated with lipopolysaccharide.
AB  - Recently, it has been reported that metformin may attenuate inflammation and
      directly act on the central nervous system. Using the HPLC method, in Wistar
      rats, we assessed the changes in metformin concentrations in various brain
      regions (pituitary gland, olfactory bulb, hypothalamus, cerebellum, hippocampus,
      striatum, frontal cortex), cerebrospinal fluid and plasma after single and
      chronic oral administration, in the model of systemic inflammation induced by
      lipopolysaccharide (ip). Regarding the influence of systemic inflammation on
      metformin distribution, the pituitary gland demonstrated the highest its level
      after single and chronic administration (28.8 +/- 3.5 nmol/g and 24.9 +/- 3.2
      nmol/g, respectively). We concluded that orally-dosed metformin rapidly crosses
      the blood-brain barrier and differently accumulates in structures of the central
      nervous system.

PMID- 21098881
TI  - Towards prediction and prioritization of disease genes by the modularity of human
      phenome-genome assembled network.
AB  - Empirical clinical studies on the human interactome and phenome not only
      illustrates prevalent phenotypic overlap and genetic overlap between diseases,
      but also reveals a modular organization of the genetic landscape of human
      disease, providing new opportunities to reduce the complexity in dissecting the
      phenotype-genotype association. We here introduce a network-module based method
      towards phenotype-genotype association inference and disease gene identification.
      This approach incorporates protein-protein interaction network, phenotype
      similarity network and known phenotype-genotype associations into an assembled
      network. We then decomposes the resulted network into modules (or communities)
      wherein we identified and prioritized the disease genes from the candidates
      within the loci associated with the query disease using a linear regression model
      and concordance score. For the known phenotype-gene associations in the OMIM
      database, we used the leave-one-out validation to evaluate the feasibility of our
      method, and successfully ranked known disease genes at top 1 in 887 out of 1807
      cases. Moreover, applying this approach on 850 OMIM loci characterized by an
      unknown molecular basis, we propose high-probability candidates for 81 genetic
      diseases.

PMID- 21098882
TI  - Stochastic simulation of the spatio-temporal dynamics of reaction-diffusion
      systems: the case for the bicoid gradient.
AB  - Reaction-diffusion systems are mathematical models that describe how the
      concentrations of substances distributed in space change under the influence of
      local chemical reactions, and diffusion which causes the substances to spread out
      in space. The classical representation of a reaction-diffusion system is given by
      semi-linear parabolic partial differential equations, whose solution predicts how
      diffusion causes the concentration field to change with time. This change is
      proportional to the diffusion coefficient. If the solute moves in a homogeneous
      system in thermal equilibrium, the diffusion coefficients are constants that do
      not depend on the local concentration of solvent and solute. However, in
      nonhomogeneous and structured media the assumption of constant intracellular
      diffusion coefficient is not necessarily valid, and, consequently, the diffusion
      coefficient is a function of the local concentration of solvent and solutes. In
      this paper we propose a stochastic model of reaction-diffusion systems, in which
      the diffusion coefficients are function of the local concentration, viscosity and
      frictional forces. We then describe the software tool Redi (REaction-DIffusion
      simulator) which we have developed in order to implement this model into a
      Gillespie-like stochastic simulation algorithm. Finally, we show the ability of
      our model implemented in the Redi tool to reproduce the observed gradient of the
      bicoid protein in the Drosophila Melanogaster embryo. With Redi, we were able to
      simulate with an accuracy of 1% the experimental spatio-temporal dynamics of the
      bicoid protein, as recorded in time-lapse experiments obtained by direct
      measurements of transgenic bicoidenhanced green fluorescent protein.

PMID- 21098883
TI  - Statin prevents chondrocyte aging and degeneration of articular cartilage in
      osteoarthritis (OA).
AB  - Recent reports have shown that statin (HMG-CoA reductase inhibitors) may have the
      potential to inhibit inflammatory arthritis. More recently, the idea that
      chondrocyte aging is closely associated with the progression of cartilage
      degeneration has been promulgated. Here, we demonstrate the potential of statin
      as protective agents against chondrocyte aging and degeneration of articular
      cartilage during the progression of osteoarthritis (OA), both in vitro and in
      vivo. The OA-related catabolic factor, IL-1beta induced marked downregulation of
      cellular activity, expression of a senescent biomarker, specific senescence
      associated beta-galactosidase activity and shortening of the cellular lifespan in
      chondrocytes. In contrast, treatment with statin inhibited the IL-1beta-induced
      production of cartilage matrix degrading .enzymes (metalloprotease-1 and -13) and
      cellular senescence in of chondrocytes in vitro. In addition, this statin
      accelerated the production of cartilage matrix proteoglycan in chondrocytes. The
      in vivo study was performed on the STR/OrtCrlj mouse, an experimental model which
      spontaneously develops an osteoarthritic process. In this mouse model, treatment
      with statin significantly reduced the degeneration of articular cartilage, while
      the control knee joints showed progressive cartilage degeneration over time.
      These findings suggest that statin may have the potential to prevent the
      catabolic stress-induced chondrocyte disability and aging observed in articular
      cartilage. Our results indicate that statin are potential therapeutic agents for
      protection of articular cartilage against the progression of OA.

PMID- 21098886
TI  - [Complications of percutaneous nephrolithotripsy in staghorn nephrolithiasis].
AB  - The aim of the study was to analyze the complications of percutaneous
      nephrolithotripsy (PCNL) in staghorn nephrolithiasis. The analysis revealed that
      in case of "full" staghorn stone risk of complications of percutaneous
      nephrolithotripsy raises twice in comparison with cases of "incomplete" staghorn
      stones. The choice of least invasive method at treatment of patients with
      staghorn nephrolithiasis is one of challenges in urological practice. Superiority
      began to belonged so-called, least invasive interventions - percutaneous
      nephrolithotripsy, extracorporal shock-wave lithotripsy and also combined
      ("sandwich" - therapy) methods. In connection with development of modern methods
      of visualization, complication of percutaneous treatment methods of staghorn
      nephrolithiasis decrease, and efficiency and possibilities of their use raise.
      The analysis revealed that in aspect of development of complications after
      percutaneous nephrolithotripsy presence of "full" staghorn stone plays defining
      role, raises risk of development of complications twice in comparison with
      patients with presence "incomplete" staghorn stones.

PMID- 21098887
TI  - Using bone cement for surgical treatment of bilateral osseous temporomandibular
      joint ankylosis.
AB  - Temporomandibular joint (TMJ) ankylosis with complete immobility of lower jaw
      represents a maximal functional impairment and causes malocclusion and impaired
      function of mastication. Main goal of surgical treatment of patients with TMJ
      ankylosis is regaining of organ function and good cosmetic results. Authors
      modified the implant of articular head by bone cement for surgical treatment of
      TMJ ankylosis (five cases). Mandibular arch osteotomy on both sides was performed
      under nasotracheal anesthesia. 1.5-2 cm bone conglomerate was removed and
      articular fossa was formed in remaining part. Titan mini plate was formed so that
      it was possible to hang it on osteotomized surface of the arch. Free surface of
      plate was faced towards the artificial articular fossa, on which the articular
      head was formed using bone cement. The plate on the other side was fixed on
      mandibular arch with screws. All cases were followed by good cosmetic and
      functional effect (period of observation 5 month-4 years). The method, despite of
      small material size is advantageous due to its good outcome, low cost and
      relatively simple surgical technique.

PMID- 21098884
TI  - Aging of the hypothalamic-pituitary-adrenal axis in nonhuman primates with
      depression-like and aggressive behavior.
AB  - We have investigated aging of the hypothalamic-pituitary-adrenal (HPA) axis in
      female rhesus monkeys that differ in adaptive behavior. Plasma cortisol (F) and
      dehydroepiandrosterone sulfate (DHEA-S) concentrations under basal conditions and
      under acute psycho-emotional stress were evaluated in blood plasma of young (6-8
      years) and old (20-27 years) female rhesus monkeys with various types of adaptive
      behavior (aggressive, depression-like, and average). We have found that the age
      related changes in the HPA axis of monkeys with depression-like behavior were
      accompanied by the maximal absolute and relative hypercortisolemia under both
      basal conditions and stress. Moreover, young aggressive monkeys, in comparison
      with young monkeys of other behavior groups, demonstrated the highest plasma
      levels of DHEA-S and the lowest molar ratios between F and DHEA-S. Thus, age
      related dysfunctions of the HPA axis are associated with adaptive behavior of
      animals.

PMID- 21098888
TI  - [X-ray methods potentialities for the diagnosis of mediastinal limphomas].
AB  - The target scientific research studies the results of clinicoroentgenological
      examination among 100 patients with mediastinal limphomas. The most typical X-ray
      and CT signs were demonstrated. The investigation proves CT to be highly
      informative method in diagnosis of mediastinal limphomas. CT provides a more
      complete picture, making it easier to diagnose problems, determine the extent of
      disease, prescribe treatment, and track progress. The mediastinal lymphomas must
      be diagnosed based on clinical, observation and laboratory, roentgenological, CT
      and morphological diagnostic testing.

PMID- 21098885
TI  - CD36 plays an important role in the clearance of oxLDL and associated age
      dependent sub-retinal deposits.
AB  - Age-related macular degeneration (AMD) represents the major cause of vision loss
      in industrialized nations. Laminar deposits in Bruch's membrane (BM) are among
      the first prominent histopathologic features, along with drusen formation, and
      have been found to contain oxidized lipids. Increases in concentrations of
      oxidized LDL (oxLDL) in plasma are observed with age and high fat high (HFHC)
      cholesterol diet. CD36 is the principal receptor implicated in uptake of oxLDL,
      and is expressed in the retinal pigment epithelium (RPE). We determined if CD36
      participates in oxLDL uptake in RPE and correspondingly in clearance of sub
      retinal deposits. Uptake of oxLDL by RPEin vitro and in vivo was CD36-dependent.
      CD36 deficiency in mice resulted in age-associated accumulation of oxLDL and sub
      retinal BM thickening, despite fed a regular diet. Conversely, treatment of HFHC
      fed ApoE null mice with a CD36 agonist, EP80317 (300 MUg/kg/day), markedly
      diminished thickening of BM, and partially preserved (in part) photoreceptor
      function. In conclusion, our data uncover a new role for CD36 in the clearance of
      oxidized lipids from BM and in the prevention of age-dependent sub-retinal
      laminar deposits.

PMID- 21098889
TI  - [Clinical-hemodynamic and anti-ischemic effects ivabradine and nebivolol ischemic
      heart disease with left ventricular dysfunction].
AB  - The aim of this study was to examine the effectiveness of Ivabradine (available
      under the brandnames of Procoralan, Coralan, Corlentor, Coraxan, "Servier",
      France) and Nebivolol (Nebilet, "Berlin-Chemie", Germany) with combination of
      standard therapy in patients with coronary artery disease and left ventricular
      dysfunction. A total of 72 patients (mean age 57.3+/-4,5 years) have been
      observed during 6 months. Patients were divided into 3 groups (standard therapy;
      standard therapy and Nebilet; standard therapy and Coraxan). The results showed
      that Coraxan with combination therapy compared optimally reduced heart rate and
      ensure a proper anti-ischemic effect, expressed as reduced left ventricular
      dysfunction, improved the degree of congestive heart failure than the group
      Nebilet.

PMID- 21098890
TI  - "Comet tail" artefact in diagnosis of pulmonary congestion in patients with
      diastolic heart failure.
AB  - The aim of this study was to evaluate the importance of thoracic ultrasound
      examination in diagnosis of DHF. Total of 380 patients with HF were evaluated. 86
      patients had diastolic HF (I group) and 294 patients had systolic HF (II group).
      The control, III group consisted of 155 patients with left ventricular diastolic
      dysfunction but without HF. HF patients did not take any medication before
      ultrasound examination. All patients underwent thoracic X ray and ultrasound
      examination. Sonographic examination of a lung was done with 3.0-4.0 MgHz convex
      or sector probe, from 10 points on thoracic wall (cross points of midclavicular
      line II, IV and V intercostal spaces and anterior axilar line with IV and V
      spaces), which corresponded to the projection of lower, middle and upper lobes of
      right lung and upper and lower lobes of left lung. During pulmonary ultrasound
      examination 95.5% of patients with HF had "Comet tail phenomenon", which was
      registered only in 35.5% patients without HF (p>0.001). In DHF group "Comet tail
      phenomenon" was registered in 91.9% and in systolic HF group in 96.6% patients.
      In 81.4% of patients with DHF "Comet tail phenomenon" was registered from 3 and
      more registration points. In control group "Comet tail" was registered from more
      than 3 points only in 2 (1.3%) patients. The best results in diagnosis of DHF can
      be achieved if we take "3 and more registration points" as a reference point for
      diagnosis of pulmonary congestion (sensitivity - 0.911, specificity - 0.942,
      positive predictive value 0,975). In patients with diastolic HF during pulmonary
      ultrasound examination significantly often was registered "Comet tail
      phenomenon". The count of registration points from the thoracic wall of "Comet
      tail phenomenon" 3 and > is sensitive and specific sign of HF. We think that lung
      sonography offers a new method for the diagnosis of decompensated diastolic HF at
      bedside and may provide important information.

PMID- 21098891
TI  - Results of conservative treatment of achillodynia with application micro-current
      therapy.
AB  - Achillodynia describes it as an expression of chronic pain in the Achilles
      tendon. Pain in the Achilles tendon can be the cause of wear and tear in the
      tendon tissue, or following an inflammation of the peritendineum, the underlying
      bursa and/or the tendon insertion at the heel bone. It often occurs after
      sporting unusual stress and heal after complex conservative treatment by rest,
      (partial) relief and physical exercise within several weeks to months. The aim
      was to turn knowledge on the effectiveness of complex conservative treatment
      measures, in particular to gain by additional stimulation in the treatment of
      Achilles tendon. 20 patients with a diagnosis of achillodynia were treated 05
      2009 to 12-2009 in the orthopedic outpatient therapy center with the help of the
      extra, micro-current therapy (CellVAS(r) device) and a complex conservative
      treatment measures. The analysis was conducted using a questionnaire, clinical
      examinations, magnetic resonance imaging (MRI) and a radiological examination of
      the Achilles tendon with the ankle joint. At the beginning and end of the
      intervention to the Board of subjective symptoms scores (NRS scale) and
      assessment of treatment results by the doctor for 4-step rating scale were
      collected. The study compares the treatment response in Achillodynia from a
      control group. The average age of patients was 46.3 years at the time of
      treatment. Of these patients: 14 (70%) were females and 6 (30%) male. Of 20
      patients were 8 (40%) patients with very good, 7 (35%) patients with good, two
      (10%) patients with satisfactory and three (15%) patients with poor results. In
      addition, 17 of 20 patients (85%) with conservative treatment measures were
      satisfied, 3 patients (15%) were dissatisfied. The subjective assessment of the
      complaints numerical rating scale (NRS scale) improved significantly (p <0.001)
      from 8.9 to 2.3 points after treatment. An objective evaluation by the attending
      physician based on various clinical parameters was assessed in 75% of the cases
      as good or very good. The study shows that the described complex conservative
      therapy is the integration of a micro-current treatment is a very good method for
      the treatment of Achillodynia/Achilles tendon disorders in athletes. The primary
      goal of treatment is to achieve freedom from pain and was achieved consistently,
      as the subjective assessment of the complaints was proved using the NRS scale.
      The high patient satisfaction with the treatment suggests in addition, any
      therapy must keep in action the long-term development of athletes in mind. In
      individual must be questioned what treatment method for long-term sports
      development but also the health history (this is not inevitably always the same)
      is an advantage. The conservative treatment seems to be advantageous because it
      leaves open for therapy-resistant complaints, the option of surgical treatment,
      and has generally very good chance of recovery.

PMID- 21098892
TI  - [Pain perception among depressed heroin addict patients].
AB  - Investigation of heroin addict patients in post-abstinent state revealed that low
      mood, anxiety, tension and guilt feeling increased sensitivity toward pain, which
      mostly experienced as algetic, coenestetick and hypochondriacal sensations.
      Algetic symptoms highly correlated with psychopathology. Efficient treatment of
      psychopathological symptoms decreased pain. It is concluded that Atypical
      antipsychotic quetiapin monotherapy could be used for treating such conditions.

PMID- 21098893
TI  - Treatment characteristics in elderly.
AB  - The pharmacodynamics and pharmacokinetics of medications, their therapeutic and
      toxic effects are age dependant. In the treatment of old people polypharmacy is
      widely used. The most common results of polypharmacy are increased adverse drug
      reactions, drug-drug interactions. In this study the use of different medications
      at the Departments of General Medicine and Cardiology (Tbilisi Republic Hospital)
      was analyzed. The case histories (1995, 2000 and 2005) of 1708 patients were
      studied. It was found that in 2005 the number of 60 years and older patients has
      doubled comparably with 1995, but the number of 24-44 years old patients remained
      almost the same. The complication rate was higher in elderly as compared with
      younger patients. It was found that in treatment of elderly population
      hypotensive drugs, diuretics and cardiac glycosides are used excessively. In the
      case of excess use of antihypertension medications there is a big risk of
      developing arterial hypotension. In old people it may lead to orthostatic
      hypotension, in youth - to dizziness. The frequent use of diuretics in old people
      may be accompanied with dehydration and risk of developing thromb formation.
      Hyponatraemia, hypokalaemia, hypomagnesemia lead to heart rhythm disturbances and
      risk of glycoside intoxication. In old people the therapeutical doses of
      diuretics depend not only on their biological activity, but also on the ability
      of their absorption from the gastrointestinal tract, on the organism's resistance
      and in the case of repeated intake on their cumulation quality and extraction.

PMID- 21098894
TI  - [Comparison of radiation background and frequency of genetic abnormalities among
      infants of Adjara foreland].
AB  - Radioecological situation of Adjara foreland and external irradiation doses of
      population have been studied. A comparison of frequency of genetic abnormalities
      (congenital abnormalities, underweight) among infants born in 2004-2008 and
      magnitude of the radiation background (RB) of region was studied to establish the
      causal connection between genetic abnormalities and RB. It was found, that
      relatively high dose of external irradiation is not the determining negative
      factor affecting the health of the newborns. At the same time, various factors of
      low intensity in nature, the magnitude of the RB and total irradiation dose
      contribute to the development of a congenital anomaly.

PMID- 21098895
TI  - Effects of oxytocin on behaviour and memory in rats subjected to chronic
      restrained stress.
AB  - We studied whether 21 days of restraint chronic stress would affect the
      contextual fear conditioning, a memory task with hippocampal-dependent components
      and anxiety- like behavior in the open field, and to determine whether oxytocin
      treatment could prevent the chronic stress induced memory and emotional
      disturbances. Restraint-stressed rats were injected daily (21 days) with oxytocin
      (1 mg/kg) or saline then tested in open field (day 22) and contextual fear
      conditioning task (days 23-24). Our data demonstrate that chronic restraint
      stress induces some behavioural changes in both saline-treated and oxytocin
      treated animals. Particularly, in the open field the animals both groups were
      characterized by hyper-locomotion. However, oxytocin-treated animals spent more
      time in the inner area of the open field, which indicates to decreased anxiety-
      related behaviour in oxytocin-treated animals versus the saline-treated ones. In
      additional restraint stress decreased freezing reaction to context, irrespective
      of whether oxytocin was given or not. Our findings indicate that during stress OT
      may be involved in the regulation of emotional behavior and memory via different
      ways. The elucidation of corresponding mechanisms is of great importance.

PMID- 21098896
TI  - [The influence of electromagnetic field on active avoidance reaction, biogenic
      amines and amino acids in brain of rats in spite of backround of food-stuff
      addition seratonus].
AB  - Amino acid preparation "Seratonus" not only regulates the action of stressors,
      but its intake in usual conditions strengthens an animals attitude toward danger,
      takes off development of excitement process, that is clearly shown by quantity
      and ratio of biogenic amines and amino acids. "Serotonus" develops optimal range
      of metabolism of above-mentioned substances that lead to right solve by animals
      of given tasks, in particular to improvement of active avoidance conditional
      reactions, that is clearly indicated by metabolism of amino acids as are
      phenylalanine and tryptophan, that is synthesizer of thirosine. While the latter
      takes part in synthesis of dopamine and noradrenalin and tryptophan regulates
      metabolism of serotonin. Hence these amines participate in improvement of memory
      processes.

PMID- 21098897
TI  - [The influence of fluoxetine on noradrenergetic neurotransmitters of brain
      cortex].
AB  - The aim of this work was to evaluate the hypothesis that the second-generation
      antidepressant, might play a role in controlling the activity of noradrenalergic
      neurotransmitters. The paper details the pharmacological profile of
      antidepressant drug Fluoxetive with high affinity for 5-HT receptor, and explains
      how the antidepressant activity chances noradrenalin reuptake inhibitor
      medications. Brain cortexes of 20 rabbits were analyzed by high-performance
      liquid chromatography. The conducted quantitative and qualitative analyzes show
      that antidepressant activity of Fluoxetine could be mediated by the synergistic
      effects on the serotoninergic and noradrenergic receptor pathways. Major
      depressive disorders are heterogeneous monoamine condition. Our studies have
      demonstrated fluoxetine efficacy and safety for treatment of major depressive
      disorders.

PMID- 21098898
TI  - Relationship between biopsy Gleason score and radical prostatectomy specimen
      Gleason score in patients undergoing sextant vs 12 core biopsies.
AB  - OBJECTIVES: Our goal is to analyze the degree of concordance between the Gleason
      score (GS) obtained in prostate biopsies and the one after radical prostatectomy.
      The intention is to know whether 12-core biopsy, instead of 6 (sextant biopsy),
      improves, or not, this correlation. METHODS: A Cohort/prevalence study was
      conducted on 128 patients who underwent prostate biopsy and subsequent radical
      prostatectomy. Patients showing biopsy Gleason values greater or equal to 6 were
      selected as candidates for radical prostatectomy. RESULTS: Mean age of the group
      of 128 patients was 62.9 years, with a mean PSA value of 8.53ng/ml. There was
      concordance between biopsy Gleason score and that obtained after radical
      prostatectomy in 63.28% of cases, while discordance was found in 36.72% of cases.
      There were not significant statistical differences after comparing results
      obtained between Gleason score concordance after 6 or 12-core biopsies and that
      obtained after radical prostatectomy. CONCLUSIONS: We have noticed a low
      correlation between Gleason score after biopsy when it was compared with that
      obtained after radical prostatectomy, while these results are similar to those
      found in the literature. We did not find better results regarding Gleason score
      correlation after biopsies performed with 12 cores instead of 6.

PMID- 21098899
TI  - [Editorial. Why a pelvic floor unit?].

PMID- 21098900
TI  - Current surgical management of severe peyronie's disease.
AB  - OBJECTIVES: To report the principles of penile resculpturing of different
      deformities caused by M. Peyronie: restoration of penile length, girth and shape
      with or without penile prosthesis implantation. METHODS: In the period between
      February 2007 and March 2009, we performed grafting surgery for M. Peyronie in 98
      patients aged between 24 and 72 years (mean 52 years). Penile deformities were
      diferent: dorsal curvature in 54 (55%), lateral in 7 (7%), ventral in 11 (11%),
      and combined curvature in 21 (21%) associated corporal narrowing was present in
      24 patients (24%). Four (4%) patients presented isolated penile shortening
      without other deformity. Isolated diffuse corporal narrowing without shortening
      was found in two (2%) patients. Severity of curvature ranges from 60 to 90
      degrees, mean 72. Thirty one (31%) patients had associated ED. Surgical options
      for severe Peyronie's disease were: single grafting in 26 pts (26%), complex
      grafting including circular tunical incision in 36 pts (36%), and in patients
      with ED the same procedures combined with penile prosthesis implantation (37 pts,
      38%). Surgical correction was based on measurement of the tunical defect and
      precise calculation of graft size and shape. Penile straightening and lengthening
      was achieved by equalizing of shortened penile side/s with the longest one
      (convex) and grafting. Penile width is reestablished with additional longitudinal
      incision/s and grafting; graft width is determined by measurement of difference
      in circumference between normal and narrowed part of the corpora. We used Intexen
      LP (AMS) as a grafting material in all cases. RESULTS: The mean follow-up was 15
      months (6-25). Mean penile length gain without prosthesis was 2.8cm (1.5-4.2) and
      with prosthesis 3.2cm (2-4.5cm). Insuficient straightening was in 5 patients (>15
      degree) where Neuro Vascular Bundle (NVB) was limiting factor. Twenty four
      patients reported hypoesthesia and reduced orgasmic sensitivity that recovered
      spontaneously after 3-6 months. De-novo ED occurred in 6 pts and progression of
      disease in 6 patients. Infection occurred only in one patient with penile
      prosthesis implantation. Overall patients' satisfaction was 95%. CONCLUSIONS:
      Complete tunical reconstruction in IPP can be performed as a safe procedure by
      transversal, longitudinal and circular grafting with or without simultaneous
      penile prosthesis implantation. Maximum penile length, girth and shape
      restoration can be achieved using geometrical calculation, regardless of type of
      deformity.

PMID- 21098901
TI  - [Current surgical management of severe peyronie's disease. Editorial comment].

PMID- 21098902
TI  - Tyrosine-kinase inhibitors in the treatment of muscle invasive bladder cancer and
      hormone refractory prostate cancer.
AB  - OBJECTIVES: Various protein kinases are known to be activated in cancer cells and
      drive tumor growth and progression. In metastatic renal cell carcinoma tyrosine
      kinase inhibitors (TKIs) have achieved significant progression-free and overall
      survival improvements. For bladder and prostate cancers TKIs may also be
      considered as a promising treatment option. Our aim was to report the most
      relevant published articles to support the interest of the use of TKIs in the
      treatment of bladder and prostate cancer. METHOD: PubMed database and
      bibliographies of retrieved articles were reviewed. The key words used were
      tyrosine-kinase inhibitor, protein-kinase inhibitor, hormone refractory prostate
      cancer, muscle invasive bladder cancer. The most relevant publications from basic
      science and clinical randomized controlled studies were summarized and analyzed.
      RESULTS: Regarding bladder cancer, TKI treatment is one of the most studied
      therapeutic strategies in the field of targeted therapy. Indeed, it has been
      suggested that targeting TK alone and/or in association with cytotoxic
      chemotherapy may represent a promising option for treating locally advanced
      and/or metastatic bladder cancer. Concerning hormone refractory prostate cancer
      (HRPC), collected data are still confusing. Basic science studies found an
      interesting expression of EGF and VEGF receptors on cancer cells supporting the
      idea that TKIs could be efficient in HRPC. Nonetheless most of published clinical
      phase II studies found a weak effect on symptoms and quality of life without any
      decrease in PSA levels or overall survival. CONCLUSION: TKIs have not yet
      achieved in bladder and prostate cancers similar efficacy to what has been
      obtained in metastatic renal cell carcinoma. Further studies are needed to
      establish the place of such an approach in non renal tumors.

PMID- 21098903
TI  - Editorial comment: Targeted therapies for genitourinary cancers: dream or
      reality?

PMID- 21098904
TI  - The performance of vasectomy in an urban municipality. Practical considerations
      for follow-up.
AB  - OBJECTIVES: To establish an adequate follow-up protocol based on time to
      azoospermia achievement after vasectomy. Also, to review the rate of
      complications in our setting. METHODS: Retrospective analysis of 391 men who
      underwent vasectomy. Follow-up was performed by means of semen analysis 6 months
      after surgery, and then every 3 months until azoospermia was achieved. Data of
      visits to the emergency unit at our centre were obtained within the first 30
      postoperative days. RESULTS: During follow-up 567 semen analysis were performed.
      From 391 vasectomy interventions, 275 had at least one semen sample available and
      valid for processing. After the first 6 months from surgery, 41.1%men still
      presented nonmotile rare sperm in semen analysis, 9.7% after 9 months, and 4.7%
      after 12 months. If semen analysis was postponed from 6 to 9 months after
      surgery, a total yearly saving of 6,153.23 Euro would be observed in our setting,
      but with the drawback of delaying the diagnosis of azoospermia in nearly 60% of
      men. Overall complication rate was 3.1%(only one man required hospital admittance
      and reintervention). No statistical difference was observed in operative time
      with regard to the presence or absence of urological complications. CONCLUSIONS:
      The percentage of men not achieving azoospermia 6 months after surgery is
      notorious. Vasectomy practice in our setting seems to be reliable and safe, with
      a limited rate of complications.

PMID- 21098905
TI  - Natural progression of embryonal carcinoma.
AB  - OBJECTIVE: We report a rare case of advanced testicular cancer that describes the
      natural progression of testicular cancer without medical treatment. This study
      also describes the effectiveness of chemotherapy, which was the approach used for
      treatment. METHODS: 37 year old male with history of mental retardation,
      presented to the emergency room with an ulcer on his right scrotum that had been
      present for a few months. He was diagnosed of pT4 embryonal carcinoma by biopsy.
      CT scan showed multiple lung nodes. He was treated with five cycles of
      Bleomycin/Etoposide/Cisplatin with complete response after treatment. RESULTS:
      Testicular tumors are the most frequent solid tumors in males between the ages of
      20 and 39 years old. Testicular tumors represent 1% of all neoplasias diagnosed
      in males and 0.1% of all male deaths due to cancer. Several studies have reported
      the current real incidence rate of testicular tumors has increased to 3%, which
      accounts for the diagnosis of 450 new cases of testicular cancer a year in Spain.
      CONCLUSIONS: The cure rate for patients with intermediate risk non-seminoma is
      around 70% following a conventional treatment approach of four cycles of BEP. The
      present case is noteworthy because, in our experience, testicular tumors are
      diagnosed at an early stage without extensively affecting the skin or simulating
      another type of epithelial tumor. As a result, the present study describes the
      natural progression of testicular cancer.

PMID- 21098906
TI  - Renal capsule leiomyoma: case report.
AB  - OBJECTIVE: We present a case of leiomyoma of the renal capsule in a 49 year-old
      woman that was detected incidentally during an abdominal study for
      gastroesophageal reflux. We discuss the clinical, radiological and pathological
      diagnosis of renal leiomyoma as well as its treatment alternatives. METHODS:
      Ultrasonography, CT and MRI were performed. A conventional pathological analysis
      including immunohistochemistry was performed after radical nephrectomy. RESULTS:
      Ultrasonography detected a solid hypoechoic mass poorly vascularized in the upper
      pole of the right kidney. CT and MRI detected a well-delimited mass showing soft
      tissue density without extension to the neighbor structures and without
      lymphadenopathies. Radical nephrectomy was performed. Microscopically, the mass
      was made of a low-grade fusocellular proliferation with cells staining with
      antibodies against smooth muscle markers. The mass was in continuity with the
      renal capsule and compressed slightly the renal parenchyma without damaging it.
      CONCLUSIONS: Renal leiomyomas are unfrequent benign tumors that should be
      suspected in young and middle aged women showing asymptomatic, well delimited and
      hypoechoic renal tumors with soft tissue density in CT scans. When vascular
      structures are not involved by the tumor, a conservative surgical intervention
      could be the first therapeutic option. Microscopically, renal leiomyomas are low
      grade fusocellular tumors showing a smooth muscle immunohistochemical profile.

PMID- 21098907
TI  - Association of crossed renal ectopia and aortic aneurism. Case report.
AB  - OBJECTIVE: Renal malformations are rare entities and rarely have clinical
      consequences. Crossed renal ectopia has an incidence of 1/2.000 autopsies. The
      association with aortic aneurysm is even more exceptional. METHODS: We present
      our case and perform a bibliographic review. RESULTS: To date and in our
      knowledge, seven cases of crossed renal ectopia associated with aortic aneurysm
      were described on the literature. This malformation makes the treatment of the
      aneurysm more complex. The possibility of renal function decrease caused by
      injuries to the renal arteries during the surgical procedure is always present.
      Because of this risk of injury of the kidney during surgery preoperative
      evaluation of the vascularization must include image technologies as the MRI, CT
      angiography or conventional arteriography. During the aortic intervention
      vascular conservation must be performed and it is necessary to minimize the time
      of renal ischemia. CONCLUSIONS: The association of crossed renal ectopia and
      aortic aneurysm is a rare event. The surgical intervention of the aorta does not
      have to necessarily originate a loss of renal function. Anyway the worsening of
      the renal clearance must be foreseen.

PMID- 21098908
TI  - Estimation of changes in volume of individual lower-limb muscles using magnetic
      resonance imaging (during bed-rest).
AB  - Muscle size in the lower limb is commonly assessed in neuromuscular research as
      it correlates with muscle function and some approaches have been assessed for
      their ability to provide valid estimates of muscle volume. Work to date has not
      examined the ability of different measurement approaches (such as cross-sectional
      area (CSA) measures on magnetic resonance (MR) imaging) to accurately track
      changes in muscle volume as a result of an intervention, such as exercise, injury
      or disuse. Here we assess whether (a) the percentage change in muscle CSA in 17
      lower-limb muscles during 56 days bed-rest, as assessed by five different
      algorithms, lies within 0.5% of the muscle volume change and (b) the variability
      of the outcome measure is comparable to that of muscle volume. We find that an
      approach selecting the MR image with the highest muscle CSA and then a series of
      CSA measures, the number of which depended upon the muscle considered,
      immediately distal and proximal, provided an acceptable estimate of the muscle
      volume change. In the vastii, peroneal, sartorius and anterior tibial muscle
      groups, accurate results can be attained by increasing the spacing between CSA
      measures, thus reducing the total number of MR images and hence the measurement
      time. In the two heads of biceps femoris, semimembranosus and gracilis, it is not
      possible to reduce the number of CSA measures and the entire muscle volume must
      be evaluated. Using these approaches one can reduce the number of CSA measures
      required to estimate changes in muscle volume by ~60%. These findings help to
      attain more efficient means to track muscle volume changes in interventional
      studies.

PMID- 21098909
TI  - A motion-compensated cone-beam CT using electrical impedance tomography imaging.
AB  - Cone-beam CT (CBCT) is an imaging technique used in conjunction with radiation
      therapy. For example CBCT is used to verify the position of lung cancer tumours
      just prior to radiation treatment. The accuracy of the radiation treatment of
      thoracic and upper abdominal structures is heavily affected by respiratory
      movement. Such movement typically blurs the CBCT reconstruction and ideally
      should be removed. Hence motion-compensated CBCT has recently been researched for
      correcting image artefacts due to breathing motion. This paper presents a new
      dual-modality approach where CBCT is aided by using electrical impedance
      tomography (EIT) for motion compensation. EIT can generate images of contrasts in
      electrical properties. The main advantage of using EIT is its high temporal
      resolution. In this paper motion information is extracted from EIT images and
      incorporated directly in the CBCT reconstruction. In this study synthetic moving
      data are generated using simulated and experimental phantoms. The paper
      demonstrates that image blur, created as a result of motion, can be reduced
      through motion compensation with EIT.

PMID- 21098910
TI  - Independent component analysis of normal and abnormal rhythm in twin pregnancies.
AB  - We investigated the utility of ICA for evaluation of fetal rhythm in five
      uncomplicated twin pregnancies and in five twin pregnancies complicated by fetal
      arrhythmia. Using objective and subjective criteria, we sought to determine how
      the signal-to-noise ratio, signal fidelity and interference rejection are
      affected when synthesizing the fetal signal using all the signal-containing ICA
      components (rank-p ICA) versus using the single dominant component (rank-1 ICA).
      The signal of each fetus was most commonly distributed over 1 or 2 ICA
      components, as previously observed in studies of singleton pregnancies; however,
      in 8 of 26 (31%) cases the signal of each fetus was distributed over 3, 4 or even
      5 ICA components. Rank-1 ICA provided the highest SNR and interference rejection,
      but at the cost of reduced signal fidelity. Our results corroborate that in twin
      pregnancies, including twin pregnancies complicated by fetal arrhythmia, rank-1
      ICA is very effective in isolating the QRS complexes of each fetus; however, it
      has some limitations when used for fetal rhythm evaluation due to signal
      distortion. Occasionally, rank-1 ICA completely separates the P-wave and the T
      wave from the QRS complex, thus requiring the mixing of several ICA components to
      achieve acceptable signal fidelity.

PMID- 21098911
TI  - Non-invasive bioimpedance of intact skin: mathematical modeling and experiments.
AB  - The functional integrity and pathology of the skin is reflected in its electrical
      impedance spectra. Non-invasive electrical impedance measurements of intact skin
      are dominated by the high impedic stratum corneum in low frequencies and with
      increasing frequency gradually comes to be dominated by viable skin. Models of
      this multi-layered organ can increase our understanding of the actual physical
      properties/dimensions and facilitate better diagnostics in certain applications.
      Therefore, a mathematical model considering conservation of charge in the various
      layers of the skin and adjacent electrodes is derived and validated with
      experimental findings; the latter was carried out on 60 young female subjects.
      The impact of the stratum corneum thickness, inundation, solvent and cohort size
      on the electrical properties is studied. Both model parameters and experimental
      conditions were adjusted for calibration and subsequent validation of the model
      with measurements. It is found that both the model's thickness of the stratum
      corneum as well as experimental soaking conditions (both time and saline
      concentration) affect the fit between the model and measurements. It is concluded
      that it is essential that the electrical properties of the skin are presented in
      the context of the ion concentration (if a moisturizer is employed) as well as
      the soaking time. Further refinements should be made to determine even more
      accurate dielectrical properties of the stratum corneum and viable skin layers by
      accounting for the true skin thickness and the heterogeneity of the skin layers
      this would be useful in applications where subtle alterations in the skin are of
      interest.

PMID- 21098912
TI  - The impact of uncertainties in the CT conversion algorithm when predicting proton
      beam ranges in patients from dose and PET-activity distributions.
AB  - The advantages of a finite range of proton beams can only be partly exploited in
      radiation therapy unless the range can be predicted in patient anatomy with <2 mm
      accuracy (for non-moving targets). Monte Carlo dose calculation aims at 1-2 mm
      accuracy in dose prediction, and proton-induced PET imaging aims at ~2 mm
      accuracy in range verification. The latter is done using Monte Carlo predicted
      PET images. Monte Carlo methods are based on CT images to describe patient
      anatomy. The dose calculation algorithm and the CT resolution/artifacts might
      affect dose calculation accuracy. Additionally, when using Monte Carlo for PET
      range verification, the biological decay model and the cross sections for
      positron emitter production affect predicted PET images. The goal of this work is
      to study the effect of uncertainties in the CT conversion on the proton beam
      range predicted by Monte Carlo dose calculations and proton-induced PET signals.
      Conversion schemes to assign density and elemental composition based on a CT
      image of the patient define a unique Hounsfield unit (HU) to tissue parameters
      relationship. Uncertainties are introduced because there is no unique
      relationship between HU and tissue parameters. In this work, different conversion
      schemes based on a stoichiometric calibration method as well as different numbers
      of tissue bins were considered in three head and neck patients. For Monte Carlo
      dose calculation, the results show close to zero (<0.5 mm) differences in range
      using different conversion schemes. Further, a reduction of the number of bins
      used to define individual tissues down to 13 did not affect the accuracy. In the
      case of simulated PET images we found a more pronounced sensitivity on the CT
      conversion scheme with a mean fall-off position variation of about 1 mm. We
      conclude that proton dose distributions based on Monte Carlo calculation are only
      slightly affected by the uncertainty on density and elemental composition
      introduced by unique assignment to each HU if a stoichiometric calibration is
      used. Calculated PET images used for range verification are more sensitive to
      conversion uncertainties causing an intrinsic limitation due to CT conversion
      alone of at least 1 mm.

PMID- 21098913
TI  - Modeling silicon diode dose response factors for small photon fields.
AB  - The dosimetry of small fields is important for the use of high resolution photon
      radiotherapy. Silicon diodes yield a high signal from a small detecting volume
      which makes them suitable for use in small fields and high dose gradients.
      Unshielded diodes used in large fields are known to give a varying dose response
      depending on the proportion of low energy scattered photons in the field.
      Response variations in small fields can be caused by both spectral variations,
      and disturbances of the local level of lateral electron equilibrium. We present a
      model that includes the effects from lack of charged particle equilibrium. The
      local spectra are calculated by use of fluence pencil kernels and divided into a
      low and a high energy component. The low energy part is treated with large cavity
      theory and the high energy part with the Spencer-Attix small cavity theory. Monte
      Carlo-derived correction factors are used to account for both the local level of
      electron equilibrium in the field, and deviations from this level in the silicon
      disk cavity. Results for field sizes ranging from 0.5 * 0.5 to 20 * 20 cm2 are
      compared to data from full Monte Carlo simulations and measurements. The achieved
      dose response accuracy is for the smallest fields 1-2%, and for larger fields
      0.5%. Spectral variations were of little importance for the small field response,
      implying that volume averaging, and to some extent interface transient effects,
      are of importance for use of unshielded diodes in non-equilibrium conditions. The
      results indicate that diodes should preferably be designed to have the thin layer
      of active volume padded in between inactive layers of the silicon base material.

PMID- 21098914
TI  - Integration of the denoising, inpainting and local harmonic B(z) algorithm for
      MREIT imaging of intact animals.
AB  - Conductivity imaging based on the current-injection MRI technique has been
      developed in magnetic resonance electrical impedance tomography. Current injected
      through a pair of surface electrodes induces a magnetic flux density distribution
      inside an imaging object, which results in additional magnetic field
      inhomogeneity. We can extract phase changes related to the current injection and
      obtain an image of the induced magnetic flux density. Without rotating the object
      inside the bore, we can measure only one component B(z) of the magnetic flux
      density B = (B(x), B(y), B(z)). Based on a relation between the internal
      conductivity distribution and B(z) data subject to multiple current injections,
      one may reconstruct cross-sectional conductivity images. As the image
      reconstruction algorithm, we have been using the harmonic B(z) algorithm in
      numerous experimental studies. Performing conductivity imaging of intact animal
      and human subjects, we found technical difficulties that originated from the MR
      signal void phenomena in the local regions of bones, lungs and gas-filled tubular
      organs. Measured B(z) data inside such a problematic region contain an excessive
      amount of noise that deteriorates the conductivity image quality. In order to
      alleviate this technical problem, we applied hybrid methods incorporating ramp
      preserving denoising, harmonic inpainting with isotropic diffusion and ROI
      imaging using the local harmonic B(z) algorithm. These methods allow us to
      produce conductivity images of intact animals with best achievable quality. We
      suggest guidelines to choose a hybrid method depending on the overall noise level
      and existence of distinct problematic regions of MR signal void.

PMID- 21098915
TI  - Using cone-beam CT projection images to estimate the average and complete
      trajectory of a fiducial marker moving with respiration.
AB  - Stereotactic body radiotherapy of lung cancer often makes use of a static cone
      beam CT (CBCT) image to localize a tumor that moves during the respiratory cycle.
      In this work, we developed an algorithm to estimate the average and complete
      trajectory of an implanted fiducial marker from the raw CBCT projection data.
      After labeling the CBCT projection images based on the breathing phase of the
      fiducial marker, the average trajectory was determined by backprojecting the
      fiducial position from images of similar phase. To approximate the complete
      trajectory, a 3D fiducial position is estimated from its position in each CBCT
      project image as the point on the source-image ray closest to the average
      position at the same phase. The algorithm was tested with computer simulations as
      well as phantom experiments using a gold seed implanted in a programmable phantom
      capable of variable motion. Simulation testing was done on 120 realistic
      breathing patterns, half of which contained hysteresis. The average trajectory
      was reconstructed with an average root mean square (rms) error of less than 0.1
      mm in all three directions, and a maximum error of 0.5 mm. The complete
      trajectory reconstruction had a mean rms error of less than 0.2 mm, with a
      maximum error of 4.07 mm. The phantom study was conducted using five different
      respiratory patterns with the amplitudes of 1.3 and 2.6 cm programmed into the
      motion phantom. These complete trajectories were reconstructed with an average
      rms error of 0.4 mm. There is motion information present in the raw CBCT dataset
      that can be exploited with the use of an implanted fiducial marker to sub
      millimeter accuracy. This algorithm could ultimately supply the internal motion
      of a lung tumor at the treatment unit from the same dataset currently used for
      patient setup.

PMID- 21098916
TI  - Terahertz spectroscopy of liver cirrhosis: investigating the origin of contrast.
AB  - We have previously demonstrated that terahertz pulsed imaging is able to
      distinguish between rat tissues from different healthy organs. In this paper we
      report our measurements of healthy and cirrhotic liver tissues using terahertz
      reflection spectroscopy. The water content of the fresh tissue samples was also
      measured in order to investigate the correlations between the terahertz
      properties, water content, structural changes and cirrhosis. Finally, the samples
      were fixed in formalin to determine whether water was the sole source of image
      contrast in this study. We found that the cirrhotic tissue had a higher water
      content and absorption coefficient than the normal tissue and that even after
      formalin fixing there were significant differences between the normal and
      cirrhotic tissues' terahertz properties. Our results show that terahertz pulsed
      imaging can distinguish between healthy and diseased tissue due to differences in
      absorption originating from both water content and tissue structure.

PMID- 21098917
TI  - Closed-form kinetic parameter estimation solution to the truncated data problem.
AB  - In a dedicated cardiac single photon emission computed tomography (SPECT) system,
      the detectors are focused on the heart and the background is truncated in the
      projections. Reconstruction using truncated data results in biased images,
      leading to inaccurate kinetic parameter estimates. This paper has developed a
      closed-form kinetic parameter estimation solution to the dynamic emission imaging
      problem. This solution is insensitive to the bias in the reconstructed images
      that is caused by the projection data truncation. This paper introduces two new
      ideas: (1) it includes background bias as an additional parameter to estimate,
      and (2) it presents a closed-form solution for compartment models. The method is
      based on the following two assumptions: (i) the amount of the bias is directly
      proportional to the truncated activities in the projection data, and (ii) the
      background concentration is directly proportional to the concentration in the
      myocardium. In other words, the method assumes that the image slice contains only
      the heart and the background, without other organs, that the heart is not
      truncated, and that the background radioactivity is directly proportional to the
      radioactivity in the blood pool. As long as the background activity can be
      modeled, the proposed method is applicable regardless of the number of
      compartments in the model. For simplicity, the proposed method is presented and
      verified using a single compartment model with computer simulations using both
      noiseless and noisy projections.

PMID- 21098918
TI  - Analytic estimates of secondary neutron dose in proton therapy.
AB  - Proton beam losses in various components of a treatment nozzle generate secondary
      neutrons, which bring unwanted out of field dose during treatments. The purpose
      of this study was to develop an analytic method for estimating neutron dose to a
      distant organ at risk during proton therapy. Based on radiation shielding
      calculation methods proposed by Sullivan, we developed an analytical model for
      converting the proton beam losses in the nozzle components and in the treatment
      volume into the secondary neutron dose at a point of interest. Using the MCNPx
      Monte Carlo code, we benchmarked the neutron dose rates generated by the proton
      beam stopped at various media. The Monte Carlo calculations confirmed the
      validity of the analytical model for simple beam stop geometry. The analytical
      model was then applied to neutron dose equivalent measurements performed on
      double scattering and uniform scanning nozzles at the Midwest Proton Radiotherapy
      Institute (MPRI). Good agreement was obtained between the model predictions and
      the data measured at MPRI. This work provides a method for estimating
      analytically the neutron dose equivalent to a distant organ at risk. This method
      can be used as a tool for optimizing dose delivery techniques in proton therapy.

PMID- 21098919
TI  - Reconstruction of conductivity using the dual-loop method with one injection
      current in MREIT.
AB  - Magnetic resonance electrical impedance tomography (MREIT) is to visualize the
      internal current density and conductivity of an electrically conductive object.
      Injecting current through surface electrodes, we measure one component of the
      induced internal magnetic flux density using an MRI scanner. In order to
      reconstruct the conductivity distribution inside the imaging object, most
      algorithms in MREIT have required multiple magnetic flux density data by
      injecting at least two independent currents. In this paper, we propose a direct
      method to reconstruct the internal isotropic conductivity with one component of
      magnetic flux density data by injecting one current into the imaging object
      through a single pair of surface electrodes. Firstly, the proposed method
      reconstructs a projected current density which is a uniquely determined current
      from the measured one-component magnetic flux density. Using a relation between
      voltage potential and current, based on Kirchhoff's voltage law, the proposed
      method is designed to use a combination of two loops around each pixel from which
      to derive an implicit matrix system for determination of the internal
      conductivity. Results from numerical simulations demonstrate that the proposed
      algorithm stably determines the conductivity distribution in an imaging slice. We
      compare the reconstructed internal conductivity distribution using the proposed
      method with that using a conventional method with agarose gel phantom
      experiments.

PMID- 21098920
TI  - Dosimetric accuracy of planning and delivering small proton therapy fields.
AB  - A detailed Monte Carlo model of a proton therapy treatment head was commissioned
      to simulate the delivery of small field proton treatments. Small fields are
      challenging in the planning and quality assurance process because of aperture
      scattering and dosimetric disequilibrium. Four patients with small fields used in
      all or parts of their treatment course were studied, including two stereotactic
      patients and two fractionated patients. For the two stereotactic patients the
      overall difference of the dose covering at least 95% of the gross tumor volume
      between the Monte Carlo calculations and the delivery was -0.2% and -1.6%,
      respectively. For the two fractionated patients the overall difference of the
      dose covering at least 95% of the clinical target volume was -3.0% and 1.0%,
      respectively. We have thus confirmed that our current planning and delivery
      process for small proton fields is accurate enough to treat small lesions in the
      patient. Furthermore, we studied the impact of field size corrections and
      identified limitations of the pencil beam algorithm for predicting hot and cold
      spots and range degradation in the target due scattering in heterogeneities. For
      the four cases studied in this paper, these limitations appear to impact
      individual field calculations, but do not have a significant impact on the
      prescribed dose over multiple fields.

PMID- 21098921
TI  - Monte Carlo simulation of microbeam radiation therapy with an interlaced
      irradiation geometry and an Au contrast agent in a realistic head phantom.
AB  - In this study, dose distribution calculations for bidirectional interlaced
      microbeam radiation therapy (BIMRT) were performed with a detailed head phantom
      model and the Monte Carlo code MCNPX. Doses were calculated in intracranial
      targets of dimensions 20 * 6.8 * 20 mm3 and 20 * 20 * 20 mm3 and surrounding
      tissue for which interlacing arrays are composed of 5 and 15 microbeams,
      respectively. Simulations were performed with a realistic head phantom and a
      homogenized head phantom of the same outer shape to study the effects of the
      structure of the realistic phantom on dose distribution and to show how important
      it is to use realistic phantoms. Depth-dose profiles and dose falloffs at the
      edges of the targets were calculated for cases with and without an Au contrast
      agent deposited in the target region and surrounding tissue. The parallel pattern
      of the microbeam arrays was preserved through the head phantom which makes it
      possible to interlace microbeam arrays even at deep seated targets. As the
      dimensions of the target volume were increased, the valley dose values increased
      with the number of microbeams. This sets limits on the size and position of the
      target. The usage of gold as a contrast agent provided a substantial increase in
      target dose and decreased the skin entrance, maximum skull bone and maximum brain
      doses inevitable to produce the desired target dose. Short dose falloffs at the
      edges of the targets were preserved for all cases.

PMID- 21098922
TI  - A constrained reconstruction technique of hyperelasticity parameters for breast
      cancer assessment.
AB  - In breast elastography, breast tissue usually undergoes large compression
      resulting in significant geometric and structural changes. This implies that
      breast elastography is associated with tissue nonlinear behavior. In this study,
      an elastography technique is presented and an inverse problem formulation is
      proposed to reconstruct parameters characterizing tissue hyperelasticity. Such
      parameters can potentially be used for tumor classification. This technique can
      also have other important clinical applications such as measuring normal tissue
      hyperelastic parameters in vivo. Such parameters are essential in planning and
      conducting computer-aided interventional procedures. The proposed parameter
      reconstruction technique uses a constrained iterative inversion; it can be viewed
      as an inverse problem. To solve this problem, we used a nonlinear finite element
      model corresponding to its forward problem. In this research, we applied Veronda
      Westmann, Yeoh and polynomial models to model tissue hyperelasticity. To validate
      the proposed technique, we conducted studies involving numerical and tissue
      mimicking phantoms. The numerical phantom consisted of a hemisphere connected to
      a cylinder, while we constructed the tissue-mimicking phantom from polyvinyl
      alcohol with freeze-thaw cycles that exhibits nonlinear mechanical behavior. Both
      phantoms consisted of three types of soft tissues which mimic adipose,
      fibroglandular tissue and a tumor. The results of the simulations and experiments
      show feasibility of accurate reconstruction of tumor tissue hyperelastic
      parameters using the proposed method. In the numerical phantom, all hyperelastic
      parameters corresponding to the three models were reconstructed with less than 2%
      error. With the tissue-mimicking phantom, we were able to reconstruct the ratio
      of the hyperelastic parameters reasonably accurately. Compared to the uniaxial
      test results, the average error of the ratios of the parameters reconstructed for
      inclusion to the middle and external layers were 13% and 9.6%, respectively.
      Given that the parameter ratios of the abnormal tissues to the normal ones range
      from three times to more than ten times, this accuracy is sufficient for tumor
      classification.

PMID- 21098923
TI  - MR-guided focused ultrasound: enhancement of intratumoral uptake of [3H]
      docetaxel in vivo.
AB  - The purpose of this study is to quantify the enhancement of [3H]-docetaxel in
      implanted prostate tumors treated with MR-guided pulsed focused ultrasound
      (MRgFUS). Human prostate cancer, LNCaP cells in 25 ul, were implanted into the
      prostates of male nude mice. The tumor growth was directly monitored on MRI. When
      the tumor reached a designated size, MRgFUS treatment was performed using a
      focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5 T GE MR
      scanner. The tumor-bearing animals were randomly divided into three groups: group
      1, MRgFUS treatment + [3H]-docetaxel; group 2, [3H]-docetaxel only and group 3,
      as a control. Animals in group 1 were treated with MRgFUS non-invasively.
      Immediately after the treatment, the animals received a single dose of tail vein
      injection of docetaxel at 15 mg kg-1 mixed with [3H]-docetaxel at 50 uCi kg-1 in
      a total volume of 150 ul. Animals in group 2 were treated the same as in group
      one, however without MRgFUS treatment. Animals in group 3 were treated as a
      control. Animals were sacrificed 30 min after i.v. injections regardless of
      whether or not they received focused ultrasound. Tumors were removed and
      processed. The radioactivity of [3H]-docetaxel in the tumor tissue was
      quantitatively measured by a liquid scintillation counter. Our study showed that
      all animals tolerated the MRgFUS treatment well. Our data showed increased (3H
      docetaxel concentration in the tumor in the MRgFUS-treated group (1079 +/- 132
      cmp/75 mg) versus those without MRgFUS treatment (524 +/- 201 cmp/75 mg) with P =
      0.037.

PMID- 21098924
TI  - Error-corrected estimation of regional kinetic parameter histograms directly from
      pet projections.
AB  - Positron emission tomography (PET) is a unique method to investigate physiology
      in the living body. Kinetic models with kinetic rate constants describe the
      dynamic radioactive tracer uptake in living tissue. If the variation of the
      kinetic parameter values within a specific tissue region could be determined
      accurately, it would give valuable quantitative information about the tissue
      heterogeneity. In this study we developed a unique method to estimate the
      variation from the regional kinetic parameter histograms. To determine the
      kinetic parameter values, we chose non-penalized maximum likelihood (ML)
      estimation due to the specific statistical error properties of the ML estimates.
      The parameter values were estimated directly from the time series of PET
      projections. The choice of the estimation method enabled us to utilize the ML
      theory in error correction. We developed a Monte Carlo approach to determine the
      regional error distributions. The true variation of the kinetic parameters could
      then be revealed by correcting the regional ML estimate histograms with the
      estimated error distributions. The method was tested with simulated data. In
      simulations both the average and the deviation of the kinetic parameters were
      determined from the error-corrected histograms with good numerical accuracy for
      the selected region of interest.

PMID- 21098925
TI  - Isocentric rotational performance of the Elekta Precise Table studied using a USB
      microscope.
AB  - The isocentric three-dimensional performance of the Elekta Precise Table was
      investigated. A pointer was attached to the radiation head of the accelerator and
      positioned at the geometric rotational axis of the head. A USB-microscope was
      mounted on the treatment tabletop to measure the table position relative to the
      pointer tip. The table performance was mapped in terms of USB-microscope images
      of the pointer tip at different table angles and load configurations. The USB
      microscope was used as a detector to measure the pointer tip positions with a
      resolution down to 0.01 mm. A new elastic model of the treatment table was
      developed. This model describes the performance of the treatment table quite well
      except from some deviations due to backlash effects. Geometric and elastic
      features are described through six parameters. These parameters are calculated
      using the linear least squares fitting technique. A new method to ensure optimal
      positioning of the table relative to the accelerator is presented. This method
      cannot eliminate systematic errors completely. To eliminate systematic errors we
      suggest that geometric and elastic models of the table and accelerator gantry arm
      are incorporated in the dose planning system.

PMID- 21098926
TI  - Sub-10 nm structures on silicon by thermal dewetting of platinum.
AB  - A study of the dewetting behavior of platinum-thin-films on silicon was carried
      out to determine how variation of dewetting parameters affects the evolution of
      film morphology and to pinpoint which parameters yielded the smallest, most
      circular features. Platinum film thickness as well as dewetting time and
      temperature were varied and the film morphology characterized by means of
      scanning electron microscopy (SEM) analysis. Two different pathways of dewetting
      predicted in the literature (Vrij 1966 Discuss. Faraday Soc. 42 23, Becker et al
      2003 Nat. Mater. 2 59-63) were observed. Depending on the initial criteria,
      restructuring of the film occurred via hole or droplet formation. With increased
      annealing time, a transition from an intermediate network structure to separated
      islands occurred. In addition, the formation of multilayered films, silicide
      crystals and nanowires occurred for certain parameters. Nevertheless, the
      dewetting behavior witnessed could be related to physical processes. Droplets
      with a mean diameter of 9 nm were formed by using a 1.5 nm thick platinum film
      annealed at 800  degrees C for 30 s. To demonstrate the suitability of the
      annealed films for further processing, we then used the dewetted films as masks
      for reactive ion etching to transfer the pattern into the silicon substrate,
      forming tapered nanopillars.

PMID- 21098927
TI  - Light non-metallic atom (B, N, O and F)-doped graphene: a first-principles study.
AB  - First-principles calculations are performed to study the geometry, electronic
      structure and magnetic properties of light non-metallic atom-doped graphene (B,
      N, O and F). The planar structure and the quasi-linear energy dispersion near the
      Dirac point remain through doping with B and N atoms, by which p-type doping and
      n-type doping graphene are respectively induced. A bandgap of about 0.5 eV is
      generated through O doping, and geometrically the O atom is also in the graphene
      plane. No magnetic moment is detected in B- , N- and O-doped graphene. For F
      doping, the F atom bonds with one of the carbon atoms close to the vacancy, with
      the other two carbon atoms undergoing a Jahn-Teller distortion. A weak polarized
      magnetic moment of 0.71 u(B) is detected through F doping.

PMID- 21098928
TI  - Development of a nanoparticulate formulation of diminazene to treat African
      trypanosomiasis.
AB  - There is a real need to develop new therapeutic strategies for African
      trypanosomiasis infections. In our study, we developed a new drug delivery system
      of diminazene (DMZ), a trypanocidal drug registered for veterinary use. This drug
      candidate presents a limited efficacy, a poor affinity for brain tissue and
      instability. The development of colloidal formulations based on a porous cationic
      nanoparticle with an oily core ((70)DGNP(+)), has potentially two advantages:
      stabilization of the drug and potential targeting of the parasite. We analyzed
      two processes of drug loading: in process (DMZ was added during the preparation
      of (70)DGNP(+) at 80  degrees C) and post-loading (DMZ was mixed with a
      (70)DGNP(+) solution at room temperature). Poor stability of the drug was
      observed using the in process technique. When using the post-loading technique
      over 80% drug entrapment efficiency was obtained at a ratio of DMZ:phospholipids
      (wt:wt) < 5%. Moreover, DMZ loaded into (70)DGNP(+) was found to be protected
      against oxidation and was stable for at least six months at 4  degrees C.
      Finally, in vitro tests on T.b. brucei showed an increased efficacy of DMZ loaded
      in (70)DGNP(+).

PMID- 21098929
TI  - Mn-doped ZnO nanocrystals embedded in Al2O3: structural and electrical
      properties.
AB  - We report on the structural and electrical properties of Mn-doped ZnO/Al(2)O(3)
      nanostructures produced by the pulsed laser deposition technique. Grazing
      incidence small angle x-ray scattering (GISAXS) and Rutherford backscattering
      spectrometry revealed the multilayered structure in as-deposited samples.
      Annealing of the nanostructures was shown to promote the formation of
      nanocrystals embedded in the Al(2)O(3) matrix, as was evidenced by GISAXS and
      high resolution transmission microscopy. Particle-induced x-ray emission analysis
      showed a doping of 8 at.% Mn in ZnO. Grazing incidence x-ray diffraction and
      Raman spectroscopy demonstrated that the nanocrystals have the pure wurtzite
      ZnMnO crystalline phase. Resonant Raman scattering displayed an increase of
      intensity of the 1LO mode as well as broadening of the 2LO mode related to the
      size effect. Capacitance-voltage measurements showed carrier retention with a
      voltage shift higher than those reported for similar systems.

PMID- 21098930
TI  - Super-long aligned TiO2/carbon nanotube arrays.
AB  - 5 mm long aligned titanium oxide/carbon nanotube (TiO(2)/CNT) coaxial nanowire
      arrays have been prepared by electrochemically coating the constituent CNTs with
      a uniform layer of highly crystalline anatase TiO(2) nanoparticles. While the
      presence of the TiO(2) coating was confirmed by scanning electron microscopy,
      transmission electron microscopy, Raman spectroscopy and x-ray diffraction, the
      resultant TiO(2)/CNT coaxial arrays were demonstrated to exhibit minimized
      recombination of photoinduced electron-hole pairs and fast electron transfer from
      the long TiO(2)/CNT arrays to external circuits. This, in conjunction with the
      aligned macrostructure, facilitates the fabrication of TiO(2)/CNT arrays for
      various device applications, ranging from photodetectors to photocatalytic
      systems. Thus, the millimeter long TiO(2)/CNT arrays represent a significant
      advance in the development of new macroscopic photoelectronic nanomaterials
      attractive for a variety of device applications beyond those demonstrated in this
      study.

PMID- 21098931
TI  - Free standing luminescent silicon quantum dots: evidence of quantum confinement
      and defect related transitions.
AB  - We report the synthesis of luminescent, free standing silicon quantum dots by dry
      and wet etching of silicon and silicon oxide core/shell nanostructures, which are
      synthesized by controlled oxidation of mechanically milled silicon. Dry and wet
      etching performed with CF(4) plasma and aqueous HF, respectively, result in the
      removal of the thick oxide shell of the core/shell nanostructures and affect an
      additional step of size reduction. HF etch is capable of producing isolated,
      spherical quantum dots of silicon with dimensions ~ 2 nm. However, the etching
      processes introduce unsaturated bonds at the surface of the nanocrystals which
      are subsequently passivated by oxygen on exposure to ambient atmosphere. The
      photoluminescence spectra of the colloidal suspensions of these nanocrystals are
      characterized by double peaks and excitation dependent shift of emission energy.
      Comparison of the structural, absorption and luminescence characteristics of the
      samples provides evidence for two competing transition processes--quantum
      confinement induced widened band gap related transitions and oxide associated
      interface state mediated transitions. The results enable us to experimentally
      distinguish between the contributions of the two different transition mechanisms,
      which has hitherto been a challenging problem.

PMID- 21098932
TI  - In vitro transcription and translation inhibition via DNA functionalized gold
      nanoparticles.
AB  - The use of gold nanoparticles (AuNPs) has been gaining momentum as vectors for
      gene silencing strategies, combining the AuNPs' ease of functionalization with
      DNA and/or siRNA, high loading capacity and fast uptake by target cells. Here, we
      used AuNP functionalized with thiolated oligonucleotides to specifically inhibit
      transcription in vitro, demonstrating the synergetic effect between AuNPs and a
      specific antisense sequence that blocks the T7 promoter region. Also, AuNPs
      efficiently protect the antisense oligonucleotide against nuclease degradation,
      which can thus retain its inhibitory potential. In addition, we demonstrate that
      AuNPs functionalized with a thiolated oligonucleotide complementary to the
      ribosome binding site and the start codon, effectively shut down in vitro
      translation. Together, these two approaches can provide for a simple yet robust
      experimental set up to test for efficient gene silencing of AuNP-DNA conjugates.
      What is more, these results show that appropriate functionalization of AuNPs can
      be used as a dual targeting approach to an enhanced control of gene expression
      inhibition of both transcription and translation.

PMID- 21098933
TI  - Direct deposition of patterned nanocrystalline CVD diamond using an electrostatic
      self-assembly method with nanodiamond particles.
AB  - Micron-sized and precise patterns of nanocrystalline CVD diamond were fabricated
      successfully on substrates using dispersed nanodiamond particles, charge
      connection by electrostatic self-assembly, and photolithography processes.
      Nanodiamond particles which had been dispersed using an attritional milling
      system were attached electrostatically on substrates as nuclei for diamond
      growth. In this milling process, poly sodium 4-styrene sulfonate (PSS) was added
      as an anionic dispersion agent to produce the PSS/nanodiamond conjugates. Ultra
      dispersed nanodiamond particles with a zeta-potential and average particle size
      of - 60.5 mV and ~ 15 nm, respectively, were obtained after this milling process.
      These PSS/nanodiamond conjugates were attached electrostatically to a cationic
      polyethyleneimine (PEI) coated surface on to which a photoresist had been
      patterned in an aqueous solution of the PSS/nanodiamond conjugated suspension. A
      selectively seeded area was formed successfully using the above process. A hot
      filament chemical vapor deposition system was used to synthesize the
      nanocrystalline CVD diamond on the seeded area. Micron-sized, thin and precise
      nanocrystalline CVD diamond patterns with a high nucleation density (3.8 +/- 0.4
      * 10(11) cm(-2)) and smooth surface were consequently fabricated.

PMID- 21098934
TI  - The influence of hydroxide on the initial stages of anodic growth of TiO2
      nanotubular arrays.
AB  - Understanding the mechanism for growing TiO(2) nanotubes is important for
      controlling the nanostructures. The hydroxide nano-islands on the Ti surface play
      a significant role at the initial stage of anodization by forming the very first
      nano-pores at the interface between hydroxide islands and substrate and
      eliminating the H(2)O electrolysis. A quantitative time dependent SEM study has
      revealed a nanotube growth process with an initial linear increase of pore
      diameter, film thickness and number of pores. During the anodization of titanium,
      different current transient curves are observed for Ti samples with or without
      hydroxide on the surface. The transient current profile has been quantitatively
      analyzed by fitting several distinctive stages based on a growth mechanism
      supported by SEM observations. It is found that a saturated cubic dependent
      equation is appropriate to fit a short current upturn due to the increase of the
      surface area.

PMID- 21098935
TI  - Localized electro-thermal processing: a new route to the patterning of magnetic
      recording media.
AB  - Previous reports have detailed the fabrication of media able to support high
      density magnetic recording in both longitudinal and perpendicular formats by the
      global rapid thermal processing of sputtered non-magnetic precursor films. During
      processing in this manner a magnetic element is released from its nitride and
      agglomerates to form a random near mono-dispersion of magnetic nano-particles.
      Here we explore, primarily through modelling and simulation, the feasibility of
      processing similarly formulated precursor media not globally but locally. We
      investigate the potential of using conducting nano-probe tips to produce, via
      electro-thermal (Joule) heating, a nano-patterned recording medium in the form of
      regular arrays of magnetic islands in a non-magnetic host. In the first instance
      we concentrate on the simplest cobalt based precursor medium for which both
      initial simulation and experimental studies indicate the formation of magnetic
      islands with dimensions of the order of the tip diameter; this is relatively
      straightforward. The results signify that if practical production scenarios can
      be devised to produce technologically significant areas of recording media by the
      rapid multi-probe repetition of this technique, then processing in this manner
      offers a promising route to areal recording densities of perhaps 5 Terabit/in(2)
      even with the simplest cobalt media. We also note that the electro-thermal
      processing method is potentially extendable to the production of a wide variety
      of magnetic materials (e.g. PtCo, FeCo, NiFe alloys) and, applied via electrical
      nano-imprinting type techniques, to the production of a wide variety of patterned
      structures.

PMID- 21098936
TI  - Flexible cold cathode with ultralow threshold field designed through wet chemical
      route.
AB  - A flexible cold cathode based on a uniform array of ZnO nanowires over carbon
      fabrics was designed via a simple wet chemical route. The structural parameters
      of the nanowires (i.e. length, diameter) as well as their arrangement over the
      carbon fibers were tailored by adjusting nutrient solution composition and growth
      duration. The optimized arrays of ZnO nanowires exhibit excellent electron
      emission performance with ultralow turn-on as well as threshold fields of 0.27
      and 0.56 V um(-1). This threshold field value is the lowest compared to any of
      the previous zinc-oxide-based cold cathodes realized through either chemical or
      vapor phase processes. In addition, the current density can reach an
      exceptionally high value of ~ 11 mA cm(-2) at an applied electric field of only
      0.8 V um(-1). Flexible electronic devices based on a field emitter cold cathode
      may thus be realized through chemical processing at low budget but having high
      efficiency.

PMID- 21098937
TI  - Formation of Ge quantum dots array in layer-cake technique for advanced
      photovoltaics.
AB  - We report a simple and manageable growth method for placing dense three
      dimensional Ge quantum dot (QD) arrays in a uniform or a graded size
      distribution, based on thermally oxidizing stacked poly-SiGe in a layer-cake
      technique. The QD size and spatial density in each stack can be modulated by
      conditions of the Ge content in poly-Si(1-x)Ge(x), oxidation, and the underlay
      buffer layer. Size-dependent internal structure, strain, and photoluminescence
      properties of Ge QDs are systematically investigated. Optimization of the
      processing conditions could be carried out for producing dense Ge QD arrays to
      maximize photovoltaic efficiency.

PMID- 21098938
TI  - Single-crystalline Ni2Ge/Ge/Ni2Ge nanowire heterostructure transistors.
AB  - In this study, we report on the formation of a single-crystalline
      Ni(2)Ge/Ge/Ni(2)Ge nanowire heterostructure and its field effect characteristics
      by controlled reaction between a supercritical fluid-liquid-solid (SFLS)
      synthesized Ge nanowire and Ni metal contacts. Scanning electron microscopy (SEM)
      and transmission electron microscopy (TEM) studies reveal a wide temperature
      range to convert the Ge nanowire to single-crystalline Ni(2)Ge by a thermal
      diffusion process. The maximum current density of the fully germanide Ni(2)Ge
      nanowires exceeds 3.5 * 10(7) A cm(-2), and the resistivity is about 88 MUOmega
      cm. The in situ reaction examined by TEM shows atomically sharp interfaces for
      the Ni(2)Ge/Ge/Ni(2)Ge heterostructure. The interface epitaxial relationships are
      determined to be [Formula: see text] and [Formula: see text]. Back-gate field
      effect transistors (FETs) were also fabricated using this low resistivity Ni(2)Ge
      as source/drain contacts. Electrical measurements show a good p-type FET behavior
      with an on/off ratio over 10(3) and a one order of magnitude improvement in hole
      mobility from that of SFLS-synthesized Ge nanowire.

PMID- 21098939
TI  - Ga+ focused-ion-beam implantation-induced masking for H2 etching of ZnO films.
AB  - Gallium implantation of ZnO by a focused-ion beam is used to create a mask for
      ZnO dry etching with hydrogen. Effects of Ga(+) fluence on the etch stop
      properties and the associated mechanisms are investigated. The fluence of 2.8 *
      10(16) cm(-2) is determined to be optimum to render the best mask quality. While
      lower fluences would cause less etching selectivity, higher fluences would cause
      erosion of the surface and particles to be precipitated on the surface after H(2)
      treatment at high temperature. In contrast to the commonly adopted gallium oxide
      formation on Si, transmission electron microscopy analysis reveals that, for the
      fluences <= 2.8 * 10(16) cm(-2), Ga(+) ions are incorporated as dopants into ZnO
      without any second phases or precipitates, indicating the Ga-doped ZnO layer
      behaves as a mask for H(2) etching due to the higher electronegativity of Ga(+)
      towards oxygen. However, for the fluences >= 4.6 * 10(16) cm(-2), the surface
      particles are responsible for the etch stop and are identified as ZnGa(2)O(4). We
      finally demonstrate a complicated pattern of 'NCKU' on ZnO by using this
      technique. The study not only helps clarify the related mechanisms, but also
      suggests a feasible extension of the etch stop process that can be applied to
      more functional material.

PMID- 21098940
TI  - The influence of direct motor-motor interaction in models for cargo transport by
      a single team of motors.
AB  - We analyze theoretically the effects of excluded-volume interactions between
      motors on the dynamics of a cargo driven by multiple motors. The model considered
      shares much in common with others recently proposed in the literature, with the
      addition of direct interaction between motors and motor back steps. The cargo is
      assumed to follow a continuum Langevin dynamics, while individual motors evolve
      following a Monte Carlo algorithm based on experimentally accessible
      probabilities for discrete forward and backward jumps, and attachment and
      detachment rates. The links between cargo and motors are considered as nonlinear
      springs. By means of numerical simulations we compute the relevant quantities
      characterizing the dynamical properties of the system, and we compare the results
      to those for noninteracting motors. We find that interactions lead to quite
      relevant changes in the force-velocity relation for cargo, with a considerable
      reduction of the stall force, and also cause a notable decrease of the run
      length. These effects are mainly due to traffic-like phenomena in the
      microtubule. The consideration of several parallel tracks for motors reduces such
      effects. However, we find that for realistic values of the number of motors and
      the number of tracks, the influence of interactions on the global parameters of
      transport of cargo are far from being negligible. Our studies also provide an
      analysis of the relevance of motor back steps on the modeling, and of the
      influence of different assumptions for the detachment rates. In particular, we
      discuss these two aspects in connection with the possibility of observing
      processive back motion of cargo at large load forces.

PMID- 21098941
TI  - Subject-specific cardiovascular system model-based identification and diagnosis
      of septic shock with a minimally invasive data set: animal experiments and proof
      of concept.
AB  - A cardiovascular system (CVS) model and parameter identification method have
      previously been validated for identifying different cardiac and circulatory
      dysfunctions in simulation and using porcine models of pulmonary embolism,
      hypovolemia with PEEP titrations and induced endotoxic shock. However, these
      studies required both left and right heart catheters to collect the data required
      for subject-specific monitoring and diagnosis-a maximally invasive data set in a
      critical care setting although it does occur in practice. Hence, use of this
      model-based diagnostic would require significant additional invasive sensors for
      some subjects, which is unacceptable in some, if not all, cases. The main goal of
      this study is to prove the concept of using only measurements from one side of
      the heart (right) in a 'minimal' data set to identify an effective patient
      specific model that can capture key clinical trends in endotoxic shock. This
      research extends existing methods to a reduced and minimal data set requiring
      only a single catheter and reducing the risk of infection and other complications
      a very common, typical situation in critical care patients, particularly after
      cardiac surgery. The extended methods and assumptions that found it are developed
      and presented in a case study for the patient-specific parameter identification
      of pig-specific parameters in an animal model of induced endotoxic shock. This
      case study is used to define the impact of this minimal data set on the quality
      and accuracy of the model application for monitoring, detecting and diagnosing
      septic shock. Six anesthetized healthy pigs weighing 20-30 kg received a 0.5 mg
      kg(-1) endotoxin infusion over a period of 30 min from T0 to T30. For this
      research, only right heart measurements were obtained. Errors for the identified
      model are within 8% when the model is identified from data, re-simulated and then
      compared to the experimentally measured data, including measurements not used in
      the identification process for validation. Importantly, all identified parameter
      trends match physiologically and clinically and experimentally expected changes,
      indicating that no diagnostic power is lost. This work represents a further with
      human subjects validation for this model-based approach to cardiovascular
      diagnosis and therapy guidance in monitoring endotoxic disease states. The
      results and methods obtained can be readily extended from this case study to the
      other animal model results presented previously. Overall, these results provide
      further support for prospective, proof of concept clinical testing with humans.

PMID- 21098942
TI  - Network-bridge structure of CdSxSe1-x nanowire-based optical sensors.
AB  - We report on the synthesis of CdS(x)Se(1-x) nanowires by pulsed-laser deposition
      and their application to optical sensors. We developed a suspended structure for
      a nanowire-based optical sensor. This structure comprised separated nanowires
      that were suspended in the desired position between two pre-patterned electrodes.
      We found from measuring photoluminescence that the direct bandgap energy of the
      nanowires changes linearly with the composition of sulfur in the nanowires. These
      findings show that the bandgap energy of the nanowires can be systematically
      modulated in the range of 1.7-2.4 eV. The cutoff wavelength of the fabricated
      optical sensors shifted toward the longer wavelength with increasing sulfur
      composition. We found that the CdS(x)Se(1-x) nanowires have sufficient potential
      for a broad band optoelectronic device involving photosensors.

PMID- 21098943
TI  - Effect of TiO2 nanotube parameters on field emission properties.
AB  - The dependence of field emission properties of titanium dioxide (TiO(2))
      nanotubes (NTs) has been studied as a function of NT diameter (D) and height (h),
      which varied in the ranges 18-500 nm and 500-12,000 nm, respectively. The studies
      showed a strong dependence of the field emission on these parameters. With an
      increase of NT diameter, the field enhancement factor increased monotonically
      from 120 to 3800; the current density also increased until D = 320 (current
      density ~ 3.8 mA cm( - 2)), with subsequent decrease for larger diameters. The
      field emission properties initially improved with NT height until h = 5 um, and
      later remained unchanged with further increases in h.

PMID- 21098944
TI  - Chlorine-doped n-type CdS nanowires with enhanced photoconductivity.
AB  - Cl-doped n-type CdS NWs with single-crystal wurtzite structure and [Formula: see
      text] growth direction were synthesized by using CdCl(2) as the dopant via a
      thermal co-evaporation method. By controlling the Cl vapor pressure during the
      growth, the conductivity of the CdS:Cl NWs can be tuned in a wide range of five
      orders of magnitude. A nano-photodetector based on the CdS:Cl NWs shows high
      sensitivity to visible light with excellent stability and reproducibility.
      Significantly, the photoconductivity of the CdS NWs is greatly enhanced by Cl
      doping and the responsivity and photoconductive gain of the CdS:Cl NWs have
      substantially increased compared with the undoped CdS NWs. Further study also
      demonstrates the polarization-dependent photoconductivity of the CdS:Cl NWs. It
      is expected that the CdS:Cl NWs with tunable optoelectronic properties will have
      important applications in high-performance nano-optoelectronic devices.

PMID- 21098945
TI  - Doped graphene electrodes for organic solar cells.
AB  - In this work graphene sheets grown by chemical vapor deposition (CVD) with
      controlled numbers of layers were used as transparent electrodes in organic
      photovoltaic (OPV) devices. It was found that for devices with pristine graphene
      electrodes, the power conversion efficiency (PCE) is comparable to their
      counterparts with indium tin oxide (ITO) electrodes. Nevertheless, the chances
      for failure in OPVs with pristine graphene electrodes are higher than for those
      with ITO electrodes, due to the surface wetting challenge between the hole
      transporting layer and the graphene electrodes. Various alternative routes were
      investigated and it was found that AuCl(3) doping on graphene can alter the
      graphene surface wetting properties such that a uniform coating of the hole
      transporting layer can be achieved and device success rate can be increased.
      Furthermore, the doping both improves the conductivity and shifts the work
      function of the graphene electrode, resulting in improved overall PCE performance
      of the OPV devices. This work brings us one step further toward the future use of
      graphene transparent electrodes as a replacement for ITO.

PMID- 21098946
TI  - High-rate low-temperature growth of vertically aligned carbon nanotubes.
AB  - We report the low-temperature growth of vertically aligned carbon nanotubes
      (CNTs) at high growth rates by a photo-thermal chemical vapour deposition (PTCVD)
      technique using a Ti/Fe bilayer film as the catalyst. The bulk growth temperature
      of the substrate is as low as 370  degrees C and the growth rate is up to 1.3 um
      min(-1), at least eight times faster than the values reported by traditional
      thermal CVD methods. Transmission electron microscopy observations reveal that as
      grown CNTs are uniformly made of highly crystalline 5-6 graphene shells with an
      approximately 10 nm outer diameter and a 5-6 nm inner diameter. The low
      temperature rapid growth of CNTs is strongly related to the unique top-down
      heating mode of PTCVD and the use of a Ti/Fe bimetallic solid solution catalyst.
      The present study will advance the development of CNTs as interconnects in
      nanoelectronics, through a CMOS-compatible low-temperature deposition method
      suitable for back-end-of-line processes.

PMID- 21098947
TI  - First-principles study of the electronic properties of wurtzite, zinc-blende, and
      twinned InP nanowires.
AB  - The electronic properties of zinc-blende, wurtzite, and rotationally twinned InP
      nanowires were studied using first-principles calculations. The results show that
      all the simulated nanowires exhibit a semiconducting character, and the band gap
      decreases with increasing the nanowire size. The band gap difference between the
      zinc-blende, wurtzite, and twinned InP nanowires and bulk InP can be described by
      DeltaE(g)(wire) = 0.88/D(1.23), DeltaE(g)(wire) = 0.79/D(1.22) and
      DeltaE(g)(twin) = 1.3/D(1.19), respectively, where D is the diameter of the
      nanowires. The valence band maximum (VBM) and conduction band minimum (CBM)
      originate mainly from the p-orbitals of the P atoms and s-orbitals of the In
      atoms at the core regions of the nanowires, respectively. The hexagonal (2H)
      stacking inside the cubic (3C) stacking has no effect on the electronic
      properties of thin InP nanowires.

PMID- 21098948
TI  - A facile shape-selective growth of ZnO nanotips and graded nanowires from its
      oriented nanorods in a saturated ZnS solution.
AB  - A facile solution-based route is developed for the preparation of distinctive ZnO
      nanostructures via a dissolution-growth of ZnO nanorods in a saturated ZnS
      solution at a water-bath temperature of 95  degrees C. In the dissolution-growth
      process, a series of novel morphologies including nanotips, tapered and graded
      nanowires can be conveniently achieved by simply changing the heating time. The
      pointed ends of the nanotips have a diameter of several nanometers, and the
      graded nanowires have a gradient change in diameter from a few to tens of
      nanometers along the longitudinal direction with the size of the thin end
      matching the Bohr exciton radius of ZnO. Furthermore, the formation mechanism
      from the ZnO nanorods to the nanotips, to the tapered and graded nanowires is
      discussed based on shape-evolution observations.

PMID- 21098949
TI  - Influence of surface effects on the pull-in instability of NEMS electrostatic
      switches.
AB  - The influence of surface effects, including residual surface stress and surface
      elasticity, on the pull-in instability of electrostatic switches in
      nanoelectromechanical systems (NEMS) is studied using an Euler-Bernoulli beam
      model. This model is inherently nonlinear due to the driving electrostatic force
      and Casimir force which become dominant at the nanoscale. Since no exact
      solutions are available for the resulting nonlinear differential equation, He's
      homotopy perturbation method (HPM) is used to get the approximate analytical
      solutions to the static bending of NEMS switches, which are validated by
      numerical solutions of the finite difference method (FDM). The results
      demonstrate that surface effects play a significant role in the selection of
      basic design parameters of NEMS switches, such as static deflection, pull-in
      voltage and detachment length. Surface effects on low-voltage actuation windows
      are also characterized for these switches. The present study is envisaged to
      provide useful insights for the design of NEMS switches.

PMID- 21098951
TI  - Room temperature amorphous to nanocrystalline transformation in ultra-thin films
      under tensile stress: an in situ TEM study.
AB  - The amorphous to crystalline phase transformation process is typically known to
      take place at very high temperatures and facilitated by very high compressive
      stresses. In this study, we demonstrate crystallization of amorphous ultra-thin
      platinum films at room temperature under tensile stresses. Using a micro-electro
      mechanical device, we applied up to 3% uniaxial tensile strain in 3-5 nm thick
      focused ion beam deposited platinum films supported by another 3-5 nm thick
      amorphous carbon film. The experiments were performed in situ inside a
      transmission electron microscope to acquire the bright field and selected area
      diffraction patterns. The platinum films were observed to crystallize
      irreversibly from an amorphous phase to face-centered cubic nanocrystals with
      average grain size of about 10 nm. Measurement of crystal spacing from electron
      diffraction patterns confirms large tensile residual stress in the platinum
      specimens. We propose that addition of the externally applied stress provides the
      activation energy needed to nucleate crystallization, while subsequent grain
      growth takes place through enhanced atomic and vacancy diffusion as an
      energetically favorable route towards stress relaxation at the nanoscale.

PMID- 21098950
TI  - Photocatalytic silver enhancement reaction for gravimetric immunosensors.
AB  - A novel microgravimetric immunosensor has been developed using TiO(2)
      nanoparticle-modified immunoassay and silver enhancement reaction. An antibody
      conjugated TiO(2) nanoparticle is bound to the AFP antigen immobilized on a
      quartz resonator. When the nanoparticles are exposed to UV light in a silver
      nitrate solution, the photocatalytic reduction of silver ions results in the
      formation of metallic silver onto the nanoparticles and induces a decrease in the
      resonance frequency. The frequency change by this photocatalytic reduction
      reaction is three orders of magnitude larger than the change by antigen binding
      alone. The efficiency of the photocatalytic reaction has been found to increase
      with the fraction of anatase crystallites in the nanoparticles and the
      concentration of the AgNO(3) solution. The results highlight the potential of the
      photocatalytic nanoparticles for the detection of low concentrations of target
      molecules using gravimetric sensors.

PMID- 21098953
TI  - Hovering and intermittent flight in birds.
AB  - Two styles of bird locomotion, hovering and intermittent flight, have great
      potential to inform future development of autonomous flying vehicles.
      Hummingbirds are the smallest flying vertebrates, and they are the only birds
      that can sustain hovering. Their ability to hover is due to their small size,
      high wingbeat frequency, relatively large margin of mass-specific power available
      for flight and a suite of anatomical features that include proportionally massive
      major flight muscles (pectoralis and supracoracoideus) and wing anatomy that
      enables them to leave their wings extended yet turned over (supinated) during
      upstroke so that they can generate lift to support their weight. Hummingbirds
      generate three times more lift during downstroke compared with upstroke, with the
      disparity due to wing twist during upstroke. Much like insects, hummingbirds
      exploit unsteady mechanisms during hovering including delayed stall during wing
      translation that is manifest as a leading-edge vortex (LEV) on the wing and
      rotational circulation at the end of each half stroke. Intermittent flight is
      common in small- and medium-sized birds and consists of pauses during which the
      wings are flexed (bound) or extended (glide). Flap-bounding appears to be an
      energy-saving style when flying relatively fast, with the production of lift by
      the body and tail critical to this saving. Flap-gliding is thought to be less
      costly than continuous flapping during flight at most speeds. Some species are
      known to shift from flap-gliding at slow speeds to flap-bounding at fast speeds,
      but there is an upper size limit for the ability to bound (~0.3 kg) and small
      birds with rounded wings do not use intermittent glides.

PMID- 21098952
TI  - Fast and robust hydrogen sensors based on discontinuous palladium films on
      polyimide, fabricated on a wafer scale.
AB  - Fast hydrogen sensors based on discontinuous palladium (Pd) films on supporting
      polyimide layers, fabricated by a cost-efficient and full-wafer compatible
      process, are presented. The films, deposited by electron-beam evaporation with a
      nominal thickness of 1.5 nm, consist of isolated Pd islands that are separated by
      nanoscopic gaps. On hydrogenation, the volume expansion of Pd brings initially
      separated islands into contact which leads to the creation of new electrical
      pathways through the film. The supporting polyimide layer provides both
      sufficient elasticity for the Pd nanoclusters to expand on hydrogenation and a
      sufficiently high surface energy for good adhesion of both film and contacting
      electrodes. The novel order of the fabrication processes involves a dicing step
      prior to the Pd deposition and stencil lithography for the patterning of
      microelectrodes. This allows us to preserve the as-deposited film properties. The
      devices work at room temperature, show response times of a few seconds and have a
      low power consumption of some tens of nW.

PMID- 21098954
TI  - Righting and turning in mid-air using appendage inertia: reptile tails,
      analytical models and bio-inspired robots.
AB  - Unlike the falling cat, lizards can right themselves in mid-air by a swing of
      their large tails in one direction causing the body to rotate in the other. Here,
      we developed a new three-dimensional analytical model to investigate the
      effectiveness of tails as inertial appendages that change body orientation. We
      anchored our model using the morphological parameters of the flat-tailed house
      gecko Hemidactylus platyurus. The degree of roll in air righting and the amount
      of yaw in mid-air turning directly measured in house geckos matched the model's
      results. Our model predicted an increase in body roll and turning as tails
      increase in length relative to the body. Tails that swung from a near orthogonal
      plane relative to the body (i.e. 0-30 degrees  from vertical) were the most
      effective at generating body roll, whereas tails operating at steeper angles
      (i.e. 45-60 degrees ) produced only half the rotation. To further test our
      analytical model's predictions, we built a bio-inspired robot prototype. The
      robot reinforced how effective attitude control can be attained with simple
      movements of an inertial appendage.

PMID- 21098955
TI  - Vortexlet models of flapping flexible wings show tuning for force production and
      control.
AB  - Insect wings are compliant structures that experience deformations during flight.
      Such deformations have recently been shown to substantially affect induced flows,
      with appreciable consequences to flight forces. However, there are open questions
      related to the aerodynamic mechanisms underlying the performance benefits of wing
      deformation, as well as the extent to which such deformations are determined by
      the boundary conditions governing wing actuation together with mechanical
      properties of the wing itself. Here we explore aerodynamic performance parameters
      of compliant wings under periodic oscillations, subject to changes in phase
      between wing elevation and pitch, and magnitude and spatial pattern of wing
      flexural stiffness. We use a combination of computational structural mechanics
      models and a 2D computational fluid dynamics approach to ask how aerodynamic
      force production and control potential are affected by pitch/elevation phase and
      variations in wing flexural stiffness. Our results show that lift and thrust
      forces are highly sensitive to flexural stiffness distributions, with performance
      optima that lie in different phase regions. These results suggest a control
      strategy for both flying animals and engineering applications of micro-air
      vehicles.

PMID- 21098956
TI  - Distributed power and control actuation in the thoracic mechanics of a robotic
      insect.
AB  - Recent advances in the understanding of biological flight have inspired
      roboticists to create flapping-wing vehicles on the scale of insects and small
      birds. While our understanding of the wing kinematics, flight musculature and
      neuromotor control systems of insects has expanded, in practice it has proven
      quite difficult to construct an at-scale mechanical device capable of similar
      flight performance. One of the key challenges is the development of an effective
      and efficient transmission mechanism to control wing motions. Here we present
      multiple insect-scale robotic thorax designs capable of producing asymmetric wing
      kinematics similar to those observed in nature and utilized by dipteran insects
      to maneuver. Inspired by the thoracic mechanics of dipteran insects, which entail
      a morphological separation of power and control muscles, these designs show that
      such distributed actuation can also modulate wing motion in a robotic design.

PMID- 21098957
TI  - Thermal soaring flight of birds and unmanned aerial vehicles.
AB  - Thermal soaring saves much energy, but flying large distances in this form
      represents a great challenge for birds, people and unmanned aerial vehicles
      (UAVs). The solution is to make use of the so-called thermals, which are
      localized, warmer regions in the atmosphere moving upward with a speed exceeding
      the descent rate of birds and planes. Saving energy by exploiting the environment
      more efficiently is an important possibility for autonomous UAVs as well.
      Successful control strategies have been developed recently for UAVs in
      simulations and in real applications. This paper first presents an overview of
      our knowledge of the soaring flight and strategy of birds, followed by a
      discussion of control strategies that have been developed for soaring UAVs both
      in simulations and applications on real platforms. To improve the accuracy of the
      simulation of thermal exploitation strategies we propose a method to take into
      account the effect of turbulence. Finally, we propose a new GPS-independent
      control strategy for exploiting thermal updrafts.

PMID- 21098958
TI  - Design and analysis of biomimetic joints for morphing of micro air vehicles.
AB  - Flight capability for micro air vehicles is rapidly maturing throughout the
      aviation community; however, mission capability has not yet matured at the same
      pace. Maintaining trim during a descent or in the presence of crosswinds remains
      challenging for fixed-wing aircraft but yet is routinely performed by birds. This
      paper presents an overview of designs that incorporate morphing to enhance their
      flight characteristics. In particular, a series of joints and structures is
      adopted from seagulls to alter either the dihedral or sweep of the wings and thus
      alter the flight characteristics. The resulting vehicles are able to trim with
      significantly increased angles of attack and sideslip compared to traditional
      fixed-wing vehicles.

PMID- 21098959
TI  - Nature-inspired flight--beyond the leap.

PMID- 21098960
TI  - From falling to flying: the path to powered flight of a robotic samara nano air
      vehicle.
AB  - This paper details the development of a nano-scale (>15 cm) robotic samara, or
      winged seed. The design of prototypes inspired by naturally occurring geometries
      is presented along with a detailed experimental process which elucidates
      similarities between mechanical and robotic samara flight dynamics. The helical
      trajectories of a samara in flight were observed to differ in-flight path and
      descent velocity. The body roll and pitch angular rates for the differing
      trajectories were observed to be coupled to variations in wing pitch, and thus
      provide a means of control. Inspired by the flight modalities of the bio-inspired
      samaras, a robotic device has been created that mimics the autorotative
      capability of the samara, whilst providing the ability to hover, climb and
      translate. A high-speed camera-based motion capture system is used to observe the
      flight dynamics of the mechanical and robotic samara. Similarities in the flight
      dynamics are compared and discussed as it relates to the design of the robotic
      samara.

PMID- 21098961
TI  - Non-equilibrium trajectory dynamics and the kinematics of gliding in a flying
      snake.
AB  - Given sufficient space, it is possible for gliding animals to reach an
      equilibrium state with no net forces acting on the body. In contrast, every
      gliding trajectory must begin with a non-steady component, and the relative
      importance of this phase is not well understood. Of any terrestrial animal
      glider, snakes exhibit the greatest active movements, which may affect their
      trajectory dynamics. Our primary aim was to determine the characteristics of
      snake gliding during the transition to equilibrium, quantifying changes in
      velocity, acceleration, and body orientation in the late phase of a glide
      sequence. We launched 'flying' snakes (Chrysopelea paradisi) from a 15 m tower
      and recorded the mid-to-end portion of trajectories with four videocameras to
      reconstruct the snake's body position with mm to cm accuracy. Additionally, we
      developed a simple analytical model of gliding assuming only steady-state forces
      of lift, drag and weight acting on the body and used it to explore effects of
      wing loading, lift-to-drag ratio, and initial velocity on trajectory dynamics.
      Despite the vertical space provided to transition to steady-state gliding, snakes
      did not exhibit equilibrium gliding and in fact displayed a net positive
      acceleration in the vertical axis, an effect also predicted by the analytical
      model.

PMID- 21098962
TI  - Exploring bird aerodynamics using radio-controlled models.
AB  - A series of radio-controlled glider models was constructed by duplicating the
      aerodynamic shape of soaring birds (raven, turkey vulture, seagull and pelican).
      Controlled tests were conducted to determine the level of longitudinal and
      lateral-directional static stability, and to identify the characteristics that
      allowed flight without a vertical tail. The use of tail-tilt for controlling
      small bank-angle changes, as observed in soaring birds, was verified. Subsequent
      tests, using wing-tip ailerons, inferred that birds use a three-dimensional flow
      pattern around the wing tip (wing tip vortices) to control adverse yaw and to
      create a small amount of forward thrust in gliding flight.

PMID- 21098963
TI  - Does the brain prefer geometrical homogeneity?
AB  - Some patients with frontotemporal lobar degeneration (FTLD) have shown the
      development of painting or musical abilities after the onset of the disease. In
      this report, we present another emergent ability. A female patient with FTLD
      showing dense atrophy of the bilateral anterior lobes and a loss of voluntary
      activity in aspects of daily living, presented with the characteristic behaviours
      when given a paper and a pair of scissors. When a shape was already drawn on the
      paper, she showed reasonable skills with the scissors, cutting without any
      hesitation. When she cut a blank piece of paper, she showed quite unique
      geometrical preferences. Her severely degenerated brain combined with her
      geometrical abilities suggests that the human brain is naturally affected by
      geometrical homogeneity.

PMID- 21098964
TI  - The contribution of the dorsolateral prefrontal cortex in full and divided
      encoding: a paired-pulse transcranial magnetic stimulation study.
AB  - This research investigated the contribution of the dorsolateral prefrontal cortex
      (DLPFC) in the attentional resources in episodic encoding for both verbal and non
      verbal material. Paired-pulse transcranial magnetic stimulations (TMS) were used
      to interfere transiently with either the left or right DLPFC during encoding
      under full attention (FA) or under divided attention (DA) in a recognition
      paradigm using words and random shapes. Participants recognized fewer items after
      TMS over the left DLPFC than over the right DLPFC during FA encoding. However,
      TMS over the left DLPFC did not impair performance when compared to sham
      condition. Conversely, participants produced fewer items after TMS over the right
      DLPFC in DA encoding compared to sham condition, but not compared to TMS over the
      left DLPFC. These effects were found for both words and random shapes. These
      results suggest that the right DLPFC play an important role in successful
      encoding with a concomitant task regardless of the type of material.

PMID- 21098965
TI  - Depressive symptoms and one year mortality among elderly patients discharged from
      a rehabilitation ward after orthopaedic surgery of the lower limbs.
AB  - The objective of the present prospective observational study is to evaluate the
      effect of depressive symptoms on 1-year mortality in a population of elderly
      patients discharged from a rehabilitation unit after orthopaedic surgery of the
      lower limbs. A total of 222 elderly inpatients were included, and stratified
      according to 12-months survival. 14 (6.3%) of the patients who were eligible for
      this study died during the 12-months period after discharge. As expected,
      patients who died were significantly older, lower cognitive performance, more
      depressive symptoms, poorer nutritional status and higher comorbidity in
      comparison to those who survived. Furthermore, they were generally more
      functionally dependent on admission to the Department, had worse functional
      recovery and were more disable at discharge, although a longer length of stay
      comparing to survived patients. In the adjusted logistic regression model, after
      adjustment for possible confounders and covariates, the presence of severe
      depressive symptoms significantly predicted a four-fold risk of death at 12
      months. The only other factor associated poor 12-months survival was comorbidity,
      that predicted a 6-fold risk of death. In conclusions this study suggests that
      severe depressive symptoms on admission predicts 1-year mortality in elderly
      patients discharged from a post-acute care unit after orthopaedic rehabilitation.

PMID- 21098966
TI  - Relationship between cognitive impairment and behavioural disturbances in
      Alzheimer's disease patients.
AB  - BACKGROUND AND AIMS: Alzheimer's disease (AD) is a neurodegenerative disorder in
      which the patients can exhibit some behavioural disturbances in addition to
      cognitive impairment. The aims of the present study were to investigate the
      relationship between severity and rate of decline of the cognitive and
      behavioural impairment in patient with AD. METHODS: 54 AD patients were assessed
      at baseline and after 12 months with the Mental Deterioration Battery (MDB), the
      Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the
      Neuropsychiatric Inventory (NPI-10). RESULTS: MDB was more accurate than ADAS-Cog
      in the early diagnosis of AD. Conversely, ADAS-Cog was more sensitive at
      revealing the progression of cognitive decline. Depression, Apathy and Anxiety
      are the most frequent and severe behavioural disturbances at baseline. At follow
      up Delusions and Irritability increased significantly. Significant correlations
      were observed between severity of cognitive impairment and behavioural disorders
      both at baseline and in the progression rate passing from T0 to T12. CONCLUSIONS:
      Severity and progression rate of behavioural and cognitive alterations in
      patients with AD are significantly associated.

PMID- 21098967
TI  - Decision making under risk condition in patients with Parkinson's disease: a
      behavioural and fMRI study.
AB  - We aimed to study whether previously described impairment in decision making
      under risky conditions in patients with Parkinson's disease (PD) is affected by
      deficits in using information about potential incentives or by processing
      feedback (in terms of fictitious gains and losses following each decision).
      Additionally, we studied whether the neural correlates of using explicit
      information in decision making under risk differ between PD patients and healthy
      subjects. We investigated ten cognitively intact PD patients and twelve healthy
      subjects with the Game of Dice Task (GDT) to assess risky decision making, and
      with an fMRI paradigm to analyse the neural correlates of information integration
      in the deliberative decision phase. Behaviourally, PD patients showed selective
      impairment in the GDT but not on the fMRI task that did not include a feedback
      component. Healthy subjects exhibited lateral prefrontal, anterior cingulate and
      parietal activations when integrating decision-relevant information. Despite
      similar behavioural patterns on the fMRI task, patients exhibited reduced
      parietal activation. Behavioural results suggest that PD patients' deficits in
      risky decision making are dominated by impaired feedback utilization not
      compensable by intact cognitive functions. Our fMRI results suggest similarities
      but also differences in neural correlates when using explicit information for the
      decision process, potentially indicating different strategy application even if
      the interfering feedback component is excluded.

PMID- 21098968
TI  - Does diabetes mellitus alter the onset and clinical course of vascular dementia?
AB  - BACKGROUND: Vascular dementia (VaD) is the second most common dementing illness.
      Multiple risk factors are associated with VaD, but the individual contribution of
      each to disease onset and progression is unclear. We examined the relationship
      between diabetes mellitus type 2 (DM) and the clinical variables of VaD. METHODS:
      Data from 593 patients evaluated between June, 2003 and June, 2008 for cognitive
      impairment were prospectively entered into a database. We retrospectively
      reviewed the charts of 63 patients who fit the NINDS-AIREN criteria for VaD. The
      patients were divided into those with DM (VaD-DM, n=29) and those without DM
      (VaD, n=34). The groups were compared with regard to multiple variables. RESULTS:
      Patients with DM had a significantly earlier onset of VaD (71.9 +/- 6.54 vs. 77.2
      +/- 6.03, p< 0.001), a faster rate of decline per year on the mini mental state
      examination (MMSE; 3.60 +/- 1.82 vs. 2.54 +/- 1.60 points, p= 0.02), and a
      greater prevalence of neuropsychiatric symptoms at the time of diagnosis (62% vs.
      21%, p=0.02). CONCLUSIONS: A history of pre-morbid DM was associated with an
      earlier onset and faster cognitive deterioration in VaD. Moreover, DM was
      associated with neuropsychiatric symptoms in patients with VaD. A larger study is
      needed to verify these associations. It will be important to investigate whether
      better glycemic control will mitigate the potential effects of DM on VaD.

PMID- 21098969
TI  - Is lesion of Exner's area linked to progressive agraphia in amyotrophic lateral
      sclerosis with dementia? An autopsy case report.
AB  - Agraphia, as a neuropsychological symptom of ALS, especially ALS with dementia
      (ALS-D), has recently attracted more attention. However, the brain lesion
      responsible has not been identified. Here we present an autopsy case of ALS-D of
      a patient with obvious agraphia, without aphasia, that also presented
      cerebrospinal degeneration with TDP-43-pathology compatible with ALS-D. Of the
      pre-motor frontal lobe cortices, degeneration and immuno-histochemical pathology
      were most obvious in the caudal area of the left middle frontal gyrus, or Exner's
      area. Assuring this area plays a pivotal role in the kanji and kana formation
      used in writing the Japanese language, this case of ALS-D showed both agraphia
      and Exner's area stressed pathological lesions. It may thus be the first case to
      indicate an intimate relationship between the neuropsychological symptoms and an
      associated lesion for ALS-D.

PMID- 21098971
TI  - Cerebrospinal fluid biomarkers and memory present distinct associations along the
      continuum from healthy subjects to AD patients.
AB  - The objective was to study the association between cerebrospinal fluid (CSF)
      levels of amyloid-beta (Abeta)(1-42), t-tau, and p-tau and cognitive performance
      along the Alzheimer's disease (AD) continuum from healthy subjects to AD patients
      and, specifically, among patients in the pre-dementia stage of the disease. A
      total of 101 subjects were studied: 19 healthy controls (CTR), 17 subjects with
      subjective memory complaints (SMC), 47 with mild cognitive impairment (MCI), and
      18 AD patients. Only memory performance significantly correlated with CSF levels
      of Abeta(1-42), t-tau, and p-tau along the AD continuum. Subgroup analyses
      revealed that in SMC patients Abeta(1-42) levels positively correlated with the
      total recall score of the Free and Cued Selective Reminding Test (FCRST) (r =
      0.666; p < 0.005), Digit Span (r = 0.752; p < 0.005), and CERAD world list
      learning (r = 0.697; p < 0.005). In MCI patients, a significant inverse
      correlation was found between the word list recall score from the CERAD and t-tau
      (r = -0.483; p < 0.005) and p-tau levels (r = -0.495; p < 0.005), as well as
      between the total recall subtest score from the FCRST and both t-tau (r = -0.420;
      p < 0.005) and p-tau levels (r = -0.422; p < 0.005). No significant correlations
      were found between other aspects of cognition and CSF levels in CTR or AD
      patients. These results indicate that memory performance is related to Abeta(1
      42) levels in SMC, while it is associated with tau in the prodromal stage of the
      disease. This suggests that in the continuum from healthy aging to AD, memory
      performance is first related with Abeta(1-42) levels and then with t-tau or p
      tau, before becoming independent of biomarker levels in the dementia stage.

PMID- 21098972
TI  - Association of a functional NOS1 promoter repeat with Alzheimer's disease in the
      VITA cohort.
AB  - NO synthase, type I (NOS-I) has been suggested to play a role in the etiology of
      Alzheimer's disease (AD). The gene encoding NOS-I harbors at least nine
      alternative first exons; in the promoter region of exon 1f, a polymorphic repeat
      (NOS1 ex1f-VNTR) has been described which influences gene expression and neuronal
      transcriptome. We have shown that short alleles of this repeat are associated
      with AD. Here, we sought to further explore this finding by investigating a
      longitudinal cohort sample from the Vienna-Transdanube-Aging (VITA) study
      consisting of 606 subjects enrolled at the age of 75 (of these, genotypes were
      available for 574 subjects) and followed up for 60 months. The ex1f-VNTR risk
      genotype was associated with AD in the total sample and at the second follow-up.
      Thus, either long alleles of NOS1 ex1f-VNTR are protective against disease or
      conversely, short alleles predispose to earlier onset of disease. As
      demonstrated, ex1f-VNTR interacted with the apolipoprotein E epsilon4 risk allele
      (OR in the presence of both risk alleles 3.63; 95% CI: 1.45-9.12). These findings
      provide further evidence for an association of NOS1 with AD.

PMID- 21098973
TI  - Cerebrospinal fluid tau in frontotemporal lobar degeneration: clinical,
      neuroimaging, and prognostic correlates.
AB  - Frontotemporal lobar degeneration (FTLD) refers to heterogeneous clinical and
      biological conditions. In FTLD, cerebrospinal fluid (CSF) tau levels have been
      reported highly variable. The aim of the present study was to evaluate whether
      CSF tau might be the hallmark of a distinct FTLD phenotype. Fifty-five FTLD
      patients, who underwent CSF analysis, were considered in the present study. In
      each patient, a wide standardized neuropsychological evaluation, and CSF tau,
      phospho-tau, and amyloid-beta (Abeta) dosages were performed. Each patient was
      followed-up to five years, and outcomes carefully recorded. In a subgroup of
      patients (n = 24), magnetic resonance imaging scanning was performed, by using
      voxel-based morphometry, for grey matter investigation. The higher the CSF tau
      levels, the worse the neuropsychological and neuroimaging pattern, mainly
      characterized by greater language disturbances and left temporal grey matter
      loss. The same pattern, even if less significant, was associated with CSF phospho
      tau, while CSF Abeta levels did not play any influence on FTLD phenotype. FTLD
      patients with high CSF tau showed poor prognosis compared to those with low CSF
      tau (p = 0.031). In FTLD, CSF tau levels might be considered a marker of
      neurodegeneration, associated with a specific clinical and neuroimaging picture,
      and significantly related to poor outcome. Further studies aimed at defining the
      biological underpinnings of these findings are warranted.

PMID- 21098974
TI  - Apolipoprotein E genotype is associated with temporal and hippocampal atrophy
      rates in healthy elderly adults: a tensor-based morphometry study.
AB  - Apolipoprotein E (ApoE) epsilon4 genotype is a strong risk factor for developing
      Alzheimer's disease (AD). Conversely, the presence of the epsilon2 allele has
      been shown to mitigate cognitive decline. Tensor-based morphometry (TBM), a novel
      computational approach for visualizing longitudinal progression of brain atrophy,
      was used to determine whether cognitively intact elderly participants with the
      epsilon4 allele demonstrate greater volume reduction than those with the epsilon2
      allele. Healthy "younger elderly" volunteers, aged 55-75, were recruited from the
      community and hospital staff. They were evaluated with a baseline and follow-up
      MRI scan (mean scan interval = 4.72 years, s.d. = 0.55) and completed ApoE
      genotyping. Twenty-seven participants were included in the study of which 16 had
      the epsilon4 allele (all heterozygous epsilon3epsilon4 genotype) and 11 had the
      epsilon2epsilon3 genotype. The two groups did not differ significantly on any
      demographic characteristics and all subjects were cognitively "normal" at both
      baseline and follow-up time points. TBM was used to create 3D maps of local brain
      tissue atrophy rates for individual participants; these spatially detailed 3D
      maps were compared between the two ApoE groups. Regional analyses were performed
      and the epsilon4 group demonstrated significantly greater annual atrophy rates in
      the temporal lobes (p = 0.048) and hippocampus (p = 0.016); greater volume loss
      was observed in the right hippocampus than the left. TBM appears to be useful in
      tracking longitudinal progression of brain atrophy in cognitively asymptomatic
      adults. Possession of the epsilon4 allele is associated with greater temporal and
      hippocampal volume reduction well before the onset of cognitive deficits.

PMID- 21098975
TI  - Tau cleavage at D421 by caspase-3 is induced in neurons and astrocytes infected
      with herpes simplex virus type 1.
AB  - Herpes Simplex Virus Type 1 (HSV-1) is ubiquitous, neurotropic, and the most
      common pathogenic causes of sporadic acute encephalitis in humans. Herpes simplex
      encephalitis is associated with a high mortality rate and significant
      neurological, neuropsychological, and neurobehavioral sequelae, which afflict
      patients for life. HSV-1 infects limbic system structures in the central nervous
      system and has been suggested as an environmental risk factor for Alzheimer's
      disease. However, the possible mechanisms that link HSV-1 infection with the
      neurodegenerative process are still largely unknown. In a previous study we
      demonstrated that HSV-1 triggers hyperphosphorylation of tau epitopes
      serine202/threonine205 and serine396/serine404 in neuronal cultures, resembling
      what occurs in neurodegenerative diseases. Therefore, the aim of the present
      study was to evaluate at the cellular level if another event associated with
      neurodegeneration, such as caspase-3 induced cleavage of tau, could also be
      triggered by HSV-1 infection in primary neuronal and astrocyte cultures. As
      expected, induction of caspase-3 activation and cleavage of tau protein at its
      specific site (aspartic acid 421) was observed by Western blot and
      immunofluorescence analyses in mice neuronal primary cultures infected with HSV
      1. In agreement with our previous study on tau hyperphosphorylation, tau cleavage
      was also observed during the first 4 hours of infection, before neuronal death
      takes place. This tau processing has been previously demonstrated to increase the
      kinetics of tau aggregation in vitro and has also been observed in
      neurodegenerative pathologies. In conclusion, our findings support the idea that
      HSV-1 could contribute to induce neurodegenerative processes in age-associated
      pathologies such as Alzheimer's disease.

PMID- 21098976
TI  - The obesity related gene, FTO, interacts with APOE, and is associated with
      Alzheimer's disease risk: a prospective cohort study.
AB  - The FTO gene has been shown to have a small but robust effect on body mass index
      (BMI) and to increase the risk for diabetes. Both high BMI and diabetes are
      vascular risk factors that might play a role in the development of Alzheimer's
      disease (AD) and dementia. Thus, our aim was to explore the impact of FTO on AD
      and dementia risk. Nine years of follow-up data was gathered from the Kungsholmen
      project, a prospective population-based study on 1,003 persons without dementia.
      Cox-regression models were used to assess the relative risks of developing AD and
      dementia (DSM-III-R criteria) according to FTO genotypes (rs9939609), taking into
      account APOE, physical inactivity, BMI, diabetes, and cardiovascular disease
      (CVD). Compared to carriers of the FTO TT-genotype, AA-carriers had a higher risk
      for AD (RR 1.58, 95% CI: 1.11-2.24) and for dementia (RR 1.48, 95% CI: 1.09-2.02)
      after adjustment for age, gender, education, and APOE genotype. This effect
      remained after additional adjustment for physical inactivity, BMI, diabetes, and
      CVD. An interaction between FTO and APOE was found, with increased risk for
      dementia for those carrying both FTO AA and APOE epsilon4. Importantly, the
      effect of the AA-genotype on dementia/AD risk seems to act mostly through the
      interaction with APOE epsilon4. Our findings suggest that the FTO AA-genotype
      increases the risk for dementia, and in particular AD, independently of physical
      inactivity, BMI, diabetes, and CVD measured at baseline. Our results are in line
      with the recently reported association between FTO and reduced brain volume in
      cognitively healthy subjects.

PMID- 21098977
TI  - Primary cerebral blood flow deficiency and Alzheimer's disease: shadows and
      lights.
AB  - Alzheimer's disease (AD) is a degenerative disorder characterized by a decreased
      regional cerebral blood flow (CBF). It is most likely that a reduction in CBF
      could displace a pathway leading to AD genesis, in so far neuron death explains a
      sustained reduction in the supply of oxygen, glucose, and nutrients.
      Nevertheless, the concept of secondary CBF deficiency cannot explain the critical
      stages of early memory loss while, on the other hand, the picture of progressive
      ischemia due to primary CBF decline sheds light on the course of AD in a most
      persuasive manner. The concept of primary CBF deficiency is even more
      strengthened by the lack of correlation between degree of dementia and amount of
      CBF. Vascular abnormalities, frequently observed to co-occur with AD, might play
      a critical role in the initiation and aggravation of AD pathology given that the
      elimination of amyloid-beta (Abeta) through a vascular route is an important
      brain Abeta clearance mechanism and its failure leads to formation of vascular
      amyloidosis and dense-core plaques. The goal of this review is to provide
      scientists comprehensive knowledge of the state-of the art influence vascular
      damage and reduced perfusion have on the final development of AD and to hopefully
      stimulate more research in this area of neuroscience.

PMID- 21098979
TI  - Plasma concentration of donepezil to the therapeutic response of Alzheimer's
      disease in Taiwanese.
AB  - Donepezil has been approved for the treatment for mild-to-moderate Alzheimer's
      disease (AD), but the therapeutic response rate varies from 20 to 60%. A higher
      oral dosage was suggested to have a better therapeutic response in reported
      results, but the plasma concentration of donepezil was not examined with respect
      to the therapeutic outcomes in those studies. Therefore, we analyzed the
      therapeutic responses, measured by neuropsychological assessments, among 70 newly
      diagnosed AD patients taking donepezil (5 mg daily) in relation to their plasma
      concentration of donepezil, apolipoprotein E genotype, and demographic
      characteristics. Our results have showed 60% of recruited AD patients improved in
      cognition, measured by Mini-Mental Status Examination (MMSE), and 57.1% in global
      status, by Clinical Dementia Rating Scale (CDR) sum of boxes (CDR-SB). In
      cognition, compared to the improving group, the clinically worsening group had a
      significantly higher donepezil concentration [p = 0.022, odds ratio (OR) = 1.024,
      95% CI = 1.003-1.045] and higher initial MMSE score (p = 0.007, OR = 1.330, 95%
      CI = 1.080-1.639). In global status, initially higher CDR-SB (p = 0.028, OR =
      2.318, 95% CI = 1.096-4.903) and initially higher MMSE (p = 0.036, OR = 1.201,
      95% CI = 1.012-1.425), not donepezil concentration (p = 0.883), were
      significantly associated with clinical worsening. Our results have indicated that
      the dosage of donepezil should be reconsidered for AD patients, especially those
      clinically worsening in cognition.

PMID- 21098978
TI  - Identification of novel candidate genes for Alzheimer's disease by autozygosity
      mapping using genome wide SNP data.
AB  - Alzheimer's disease (AD) is highly prevalent in Wadi Ara despite the low
      frequency of apolipoprotein E epsilon4 in this genetically isolated Arab
      community in northern Israel. We hypothesized that the reduced genetic
      variability in combination with increased homozygosity would facilitate
      identification of genetic variants that contribute to the high rate of AD in this
      community. AD cases (n = 124) and controls (n = 142) from Wadi Ara were genotyped
      for a genome-wide set of more than 300,000 single nucleotides polymorphisms
      (SNPs) which were used to calculate measures of population stratification and
      inbreeding, and to identify regions of autozygosity. Although a high degree of
      relatedness was evident in both AD cases and controls, controls were
      significantly more related and contained more autozygous regions than AD cases (p
      = 0.004). Eight autozygous regions on seven different chromosomes were more
      frequent in controls than the AD cases, and 116 SNPs in these regions, primarily
      on chromosomes 2, 6, and 9, were nominally associated with AD. The association
      with rs3130283 in AGPAT1 on chromosome 6 was observed in a meta-analysis of seven
      genome-wide association study (GWAS) datasets. Analysis of the full Wadi Ara GWAS
      dataset revealed 220 SNP associations with AD at p <= 10-5, and seven of these
      were confirmed in the replication GWAS datasets (p < 0.05). The unique population
      structure of Wadi Ara enhanced efforts to identify genetic variants that might
      partially explain the high prevalence of AD in the region. Several of these
      variants show modest evidence for association in other Caucasian populations.

PMID- 21098980
TI  - Sharing pathogenetic mechanisms between acute myocardial infarction and
      Alzheimer's disease as shown by partially overlapping of gene variant profiles.
AB  - Gene variants that promote inflammation and cholesterol metabolism have been
      associated with acute myocardial infarction (AMI) and Alzheimer's disease (AD).
      We investigated a panel of relevant polymorphisms to distinguish genetic
      backgrounds for AMI and AD: IL10 -1082G/A, IL6 -174G/C, TNF -308G/A, IFNG
      +874T/A, SERPINA3 -51G/T, HMGCR -911C/A, APOE epsilon2/3/4 (280 AMI cases, 257 AD
      cases, and 1307 population controls, all Italian (presumed risk alleles are shown
      in bold). Six genetic risk sets I to VI were identified by fuzzy latent
      classification: I had low risk; II and III had low risk before age 65 (II, III);
      low risk sets lacked pro-inflammatory alleles for HMGCR-TNF-APOE. Pro
      inflammatory alleles for SERPINA3-IL10-IFNG were found for high risk sets IV to
      VI. Set IV 'AMI < age 40, AD < age 65' included risk alleles for HMGCR. Set V
      'AMI over a broad range of age' included risk alleles for TNF+IL6. Set VI 'AMI at
      ages 40 to 55, AD ages 65+' included APOE epsilon4. Close resemblance to the high
      risk sets, as indicated by membership scores close to one, defined high relative
      risks. We conclude that AMI and AD share genetic backgrounds involving
      cholesterol metabolism and the upregulation of inflammation and that gene-gene
      interactions in relevant sets of genes may be useful in defining inherited risk
      for common disorders.

PMID- 21098981
TI  - The reduction of baseline serotonin 2A receptors in mild cognitive impairment is
      stable at two-year follow-up.
AB  - We previously demonstrated a 20-30% reduction in cortical 5-HT2A receptor binding
      in patients with mild cognitive impairment (MCI) as compared to healthy subjects.
      Here we present a two-year follow-up of 14 patients and 12 healthy age-matched
      subjects. Baseline and follow-up partial volume corrected levels of 5-HT2A in
      four neocortical lobes and the posterior cingulate gyrus were investigated using
      [18F]altanserin positron emission tomography with a bolus-infusion approach. In
      the two-year follow-up period, 8 of 14 patients with MCI had progressed to
      fulfill diagnostic criteria for probable Alzheimer's disease (AD). In both
      patients and healthy subjects, no significant change in 5-HT2A receptor binding
      was found as compared to baseline values. In MCI patients, the average BPP in
      neocortex ranged from 1.49 to 2.45 at baseline and 1.38 to 2.29 at two-year
      follow-up; and in healthy subjects BPP ranged from 1.85 to 3.10 at baseline and
      1.81 to 2.98 at two-year follow-up. The BPP of the patients that converted to AD
      during the follow-up period did not differ significantly from the patients that
      had not (yet) converted, neither at baseline, nor at follow-up. We conclude that
      the reduced levels of 5-HT2A receptor binding in MCI patients decrease only
      slowly and non-significantly, even in patients who convert to AD. Our finding
      suggests that profoundly reduced cortical 5-HT2A receptor binding is an early
      feature in MCI whereas the clinical progression from MCI to AD is less associated
      with further decrease in binding.

PMID- 21098983
TI  - Depression and Alzheimer's disease: is stress the initiating factor in a common
      neuropathological cascade?
AB  - The existence of a high co-morbidity between Alzheimer's disease (AD) and
      depression has been known for a long time. More interesting though are recent
      studies indicating that depression and number of depressive episodes earlier in
      life is associated with increased risk of AD development. This suggests the
      existence of common neuropathological mechanisms behind depression and AD. Here
      we propose that the brain changes associated with depressive episodes that
      compromise the brain's ability to cope with stress may constitute risk factors
      for development of AD. Furthermore, in individuals with a genetic linkage to
      depression, there may be an increased vulnerability towards the initiation of a
      detrimental neurodegenerative cascade. The following review will deal with the
      various observations reported within the different neurobiological systems known
      to be involved and affected in depression, like serotonergic and cholinergic
      system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic
      factor, and discussed in relation to AD.

PMID- 21098982
TI  - A noradrenergic lesion exacerbates neurodegeneration in a Down syndrome mouse
      model.
AB  - Individuals with Down syndrome (DS) acquire Alzheimer's-like dementia (AD) and
      associated neuropathology earlier and at significantly greater rates than age
      matched normosomic individuals. However, biological mechanisms have not been
      discovered and there is currently limited therapy for either DS- or AD-related
      dementia. Segmental trisomy 16 (Ts65Dn) mice provide a useful model for many of
      the degenerative changes which occur with age in DS including cognitive deficits,
      neuroinflammation, and degeneration of basal forebrain cholinergic neurons. Loss
      of noradrenergic locus coeruleus (LC) neurons is an early event in AD and in DS,
      and may contribute to the neuropathology. We report that Ts65Dn mice exhibit
      progressive loss of norepinephrine (NE) phenotype in LC neurons. In order to
      determine whether LC degeneration contributes to memory loss and
      neurodegeneration in Ts65Dn mice, we administered the noradrenergic neurotoxin N
      (2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 2 doses of 50 mg/kg, i.p.) to
      Ts65Dn mice at four months of age, prior to working memory loss. At eight months
      of age, Ts65Dn mice treated with DSP-4 exhibited an 80% reduction in hippocampal
      NE, coupled with a marked increase in hippocampal neuroinflammation.
      Noradrenergic depletion also resulted in accelerated cholinergic neuron
      degeneration and a further impairment of memory function in Ts65Dn mice. In
      contrast, DSP-4 had minimal effects on normosomic littermates, suggesting a
      disease-modulated vulnerability to NE loss in the DS mouse model. These data
      suggest that noradrenergic degeneration may play a role in the progressive memory
      loss, neuroinflammation, and cholinergic loss occurring in DS individuals,
      providing a possible therapeutic avenue for future clinical studies.

PMID- 21098985
TI  - Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood
      brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron
      cell death.
AB  - There is growing evidence to support the hypothesis that statins may act as
      neuroprotectants in several neuropathological conditions, including Alzheimer's
      disease. The mechanisms for neuroprotection are only partially understood,
      however, and pleiotropic phenomena could be involved. We have made a comparative
      study of 9 statins (lovastatin, mevastatin, pravastatin, simvastatin,
      cerivastatin, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin),
      analyzing several parameters that could be related to neuroprotection, such as
      chemical structure, lipophilicity, potential blood-brain-barrier penetration
      (BBB), 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibition, cholesterol
      modulation in neurons, glia, and human hepatocyte cell lines, and protection
      against neurodegeneration caused by tau hyperphosphorylation induced by okadaic
      acid. Our results indicate that monacolin J derivatives (natural and semi
      synthetic statins) are the best candidates for the prevention of
      neurodegenerative conditions due to their higher potential BBB penetration
      capacity, cholesterol lowering effect on neurons with a satisfactory safety
      profile, and in vitro protection against cell death caused by okadaic acid in
      culture. Among the nine statins studied, simvastatin presented the best
      characteristics for preventing neurodegenerative conditions.

PMID- 21098986
TI  - Impairments in brain-to-blood transport of amyloid-beta and reabsorption of
      cerebrospinal fluid in an animal model of Alzheimer's disease are reversed by
      antisense directed against amyloid-beta protein precursor.
AB  - The blood-brain barrier (BBB) influences brain levels of amyloid-beta (Abeta) by
      transporting Abeta out of the brain (efflux) and by the reabsorption of
      cerebrospinal fluid (CSF) into the blood stream (bulk flow). In Alzheimer's
      disease (AD) and normal aging, unknown factors impair Abeta efflux and bulk flow
      in aging and in AD. These impairments have been proposed as mechanisms by which
      the Abeta burden in brain can increase. Impairment in Abeta efflux occurs in
      animal models of AD, including the aged SAMP8 mouse. Here, we show that CSF
      reabsorption is also reduced by about 50% in SAMP8 mice (p < 0.05). We then
      determined whether an antisense directed at the Abeta region of the amyloid-beta
      protein precursor (AbetaPP) and previously shown to decrease brain levels of
      AbetaPP and to reverse the cognitive impairments of the SAMP8 mouse was able to
      reverse these impairments. We found that the antisense restored both the CSF
      reabsorption, more than doubling the rate of efflux, and the saturable efflux of
      Abeta. These findings suggest that AbetaPP/Abeta itself contributes to the
      impairments in bulk flow and saturable efflux of Abeta and that reduction of
      AbetaPP/Abeta levels can restore normal function of the BBB.

PMID- 21098988
TI  - Vision disturbance after TBI.

PMID- 21098989
TI  - The basic anatomy of the optic nerve and visual system (or, why Thoreau was
      wrong).

PMID- 21098990
TI  - Traumatic brain injury and visual dysfunction: a limited overview.

PMID- 21098991
TI  - The vision clinic: an interdisciplinary method for assessment and treatment of
      visual problems after traumatic brain injury.

PMID- 21098992
TI  - Vision examination of TBI patients in an acute rehabilitation hospital.

PMID- 21098993
TI  - Evaluation and treatment of some common medical eye conditions encountered in
      patients with TBI, stroke and other neurological conditions in an acute care
      rehabilitation hospital.

PMID- 21098994
TI  - Double vision caused by neurologic disease and injury.

PMID- 21098995
TI  - A new prism use for treatment of cyclo-deviation in trochlear nerve injury.
AB  - Visual problems are common in patients with severe TBI. Diplopia is among the
      most frustrating of visual disturbances for patients, due to its functional
      consequences. This is further compounded by often slow, and at times, incomplete
      or partial recovery over six months or longer. Ocular cranial nerve injuries
      (particularly trochlear nerve) occur in 0.2%-1.4% of severe TBI patients. This
      paper presents a new prism treatment application for treating rotational diplopia
      arising from Trochlear nerve injury.

PMID- 21098996
TI  - Practical clinical treatment strategies for evaluation and treatment of visual
      field loss and visual inattention.

PMID- 21098997
TI  - Visual perceptual deficiencies in the brain injury population: management from
      start to finish.

PMID- 21098998
TI  - Neuropsychological assessment for visually impaired persons with traumatic brain
      injury.

PMID- 21099000
TI  - A standardized fracture reduction model for long bones--implication and
      evaluation in the femur.
AB  - Fractures of the femoral bone are frequent injuries with a wide range of affected
      individuals. New treatment strategies and technologies are being explored
      permanently. Their quality is biomechanically judged by the accuracy of the
      anatomical reduction. Malalignment of the fragments would have an eminent impact
      on the overall outcome and rehabilitation. To establish a method for
      investigations of the reduction results of femoral fractures, we developed a
      model, using a navigation system for taking measurement. The dynamic reference
      bases (DRBs) were mounted to the intact femoral bone and registered as the
      reference position. A special construction allowed removal and reattachment of
      the DRBs without provoking change in the DRB-bone system. The model was evaluated
      in its constancy. Translational deviations remained below 0.9 mm and rotational
      deviations below 0.3 degrees  after 40 repetitive reattachments. The model could
      prove to be valid and reliable. An application in long-bone trauma research is
      reasonable.

PMID- 21099001
TI  - Nursing activity recognition using an inexpensive game controller: An application
      to infection control.
AB  - It is estimated that 10% of the patients admitted to North American hospitals die
      of hospital acquired infections. Approximately half of these are thought to be a
      consequence of poor hand hygiene practices by the hospital staff. Electronic hand
      washing reminders that prompt caregivers to wash their hands before and after the
      patient/patient's environment contact may help to increase the hand hygiene
      compliance rate. However, the current systems fail to identify the nursing
      procedures happening around the patient to issue proper hand hygiene prompt. In
      this research we used the hardware of a low-cost wireless Sony game controller,
      which included a 3-axis accelerometer, to identify six nursing activities
      happening around a patient. We attached five sensors to eight nurses' left and
      right wrists, left and right upper arms, and the backs. Each nurse performed 10
      trials of each nursing activity in sequence, followed by a combined nursing
      activities trial. We extracted mean, standard deviation, energy, and correlation
      among axes per sensor and compared the results of 1-Nearest Neighbour (1-NN),
      Decision Tree (J48), and Naive Bayes classifiers. 1-NN classifier had the best
      performance and on average regardless of the sensor locations, we achieved 84% +/
      2% accuracy.

PMID- 21099002
TI  - An agent-based modelling tool (ABMT) for scheduling diagnostic imaging machines.
AB  - We present an Agent-Based Modelling Tool (ABMT) for scheduling patients at a
      diagnostic imaging facility. The ABMT accommodates multiple diagnostic imaging
      devices, a variety of patient classes, and an uneven distribution of server
      availability. The tool was tested using data and expertise from a hospital in
      Ontario, Canada. We show that the tool was able to identify a previously
      undetected increase in patient arrivals, establishing its effectiveness as a
      management tool.

PMID- 21099003
TI  - Detection of epileptic-seizures by means of power spectrum analysis of heart rate
      variability: a pilot study.
AB  - OBJECTIVE: To investigate whether epileptic seizures could be predicted or
      detected by means of spectral analysis of heart rate variability (HRV). METHODS:
      Six patients with temporal lobe epilepsy (4 females, 2 males) participated in the
      prospective pilot study while enrolled for video/EEG monitoring (24 h/day, 2-4
      days). ECG was continuously recorded and 30 min seizure-sessions (25-30 min pre
      seizure to 30 sec-5 min post-seizure onset) and 30 min non-seizure-sessions (day-
      and night sessions for each patient, as control) were chosen for further HRV
      analysis. Low frequency (LF) (0.04-0.15 Hz), High frequencies (HF) (0.15-0.40
      Hz), LF/HF, LF/(LF+HF) and reciprocal HF-power was determined using continuous
      FFT- spectral analysis of 64 R-R interval windowing with maximum overlapping.
      RESULTS: Six seizures were recorded and analyzed from three patients (2 females,
      1 male). All of the analyzed EEG-correlated seizures showed reciprocal HF-power
      peaks between 10 sec pre seizure-onset and 24 sec post seizure-onset with peak
      amplitudes 2.96-93.63 times higher than control maximum peak. For the other
      parameters we could not find significant difference between seizure and non
      seizure sessions. CONCLUSION: Specifically high reciprocal HF-power peaks suggest
      suppressed parasympathetic activity just around seizure-onset time. Seizure
      detection using HRV-analysis seems to be a promising method for non-invasive
      seizure detection in the early phase of the clinical event (even preceding the
      onset).

PMID- 21099005
TI  - Mining, knowledge and decision support.
AB  - Decision support systems (DSS) are software entities that assist the physician in
      the decision making process. They have found application in medicine due to the
      large amounts of data (e.g. laboratory measurements such as blood pressure, heart
      rate, body-mass index) and information (e.g. patient history, population
      statistics based on age and sex) that must be considered before diagnosing any
      disease or recommending a therapy. A well known example is the embedded software
      in defibrillators which allows a 'shock' to be delivered, by analyzing the
      electrocardiogram for known conditions (heart attack). The shock can restart the
      heart and timely delivery can resuscitate the patient. As well as assisting in
      primary diagnosis, a DSS can reduce medical error, assist compliance with
      clinical guidelines, improve efficiency of care delivery and improve quality of
      care. Decision support still has significant acceptance issues in clinical
      routine, but can achieve more prominence, as systems are demonstrated to provide
      effective knowledge based support. Data mining is often used to provide some
      insight to a data set and update our accepted knowledge. In this section, we
      discuss a study which examines where electrocardiographic information should be
      recorded from a patient's torso in order to increase diagnostic yield.

PMID- 21099006
TI  - Electrograms (ECG, EEG, EMG, EOG).
AB  - There is a constant need in medicine to obtain objective measurements of physical
      and cognitive function as the basis for diagnosis and monitoring of health. The
      body can be considered as a chemical and electrical system supported by a
      mechanical structure. Measuring and quantifying such electrical activity provides
      a means for objective examination of heath status. The term electrogram, from the
      Greek electro meaning electricity and gram meaning write or record, is the broad
      definition given to the recording of electrical signal from the body. In order
      that comparisons of electrical activity can be made against normative data,
      certain methods and procedures have been defined for different electrograms. This
      paper reviews these methods and procedures for the more typical electrograms
      associated with some of the major organs in the body, providing a first point of
      reference for the reader.

PMID- 21099007
TI  - Workload, health complaints, and the depressive state of workers. From the
      editor.

PMID- 21099008
TI  - Relationship among workload, health complaints, and depressive state of workers
      as revealed using a questionnaire survey.
AB  - OBJECTIVE: Identifying the relationship between workload content and health
      complaints would likely aid the establishment of preventative health care
      strategies. PARTICIPANTS: The study population consisted of 137 male workers from
      a pharmaceutical company. METHODS: The workloads of the target subjects were
      divided into three groups (A, B, and C+D) according to the scores of a self
      administered questionnaire. The results of General Health Questionnaire (GHQ, 12
      items version) for assessing health complaints were also analyzed. RESULTS: The
      percentages of workers who reported feelings of stress in response to overtime
      work, irregular work, business trips, nighttime work, no rest and/or no nap,
      mental workload, and physical workload were 22.6%, 15.3%, 2.9%, 8.0%, 13.9%,
      58.3%, and 18.2%, respectively. The significant odds ratio of workload predicting
      health complaints was 6.9 for subjects in group B and 13.9 for subjects in group
      C+D. Among them, the significant odds ratios of mental workload predicting health
      complaints and a positive GHQ were 5.7 and 4.0, respectively. Having no regular
      exercise also resulted in ORs of greater than 3 for health complaints and a
      positive GHQ. CONCLUSIONS: To cope with the health complaints of workers, mental
      health support by reducing individual workloads is recommended.

PMID- 21099009
TI  - Two-year outcome of a multidisciplinary vocational rehabilitation programme
      focused on range of motion of the neck and back.
AB  - PURPOSE: To investigate whether improvement of range of motion (ROM) in persons
      with musculoskeletal disorders, mainly neck and back pain, was associated with a
      favourable development regarding physical disability, pain, and health-related
      quality of life (QoL), and whether such development differed between sick-listed
      and non-sick-listed persons during and up to 2 years after a multidisciplinary
      rehabilitation programme. METHODS: Ten persons with full-time sick leave (Group
      I) and 49 with part-time or no sick leave (Group II) at the end of a previous
      study participated. It was shown in that study that Group I had higher pain
      rating and higher subjective physical disability than Group II, with little or no
      improvement during and after rehabilitation. In the present study, all
      participants were evaluated with neck and back mobility tests: Disability Rating
      Index (DRI); Pain Intensity Rating on a visual analogue scale (VAS); and Global
      Self-Efficacy Index (GSI). RESULTS: Cervical and thoracolumbar spine ROM were
      lower in Group I than in Group II from the start of rehabilitation to a 2-year
      follow-up. Only Group II showed a temporal improvement in ROM. No changes in DRI,
      VAS or GSI were found in parallel with corresponding temporal changes in any of
      the ROM. CONCLUSION: Group II but not Group I improved in active ROM during
      rehabilitation; further, in Group I active ROM in the cervical and thoracolumbar
      spine did not improve during the 2-year follow-up. Improvement of ROM showed no
      correlation with physical disability, pain or QoL.

PMID- 21099010
TI  - Perceptions of a computer-based instruction system in special education: high
      school teachers and students views.
AB  - OBJECTIVE: Researchers investigated how one type of computer-based instruction
      (CBI)--Kurzweil 3000 (K-3000), was perceived to affect the reading, functional
      task performance, and academic self-perception of high school students with
      special needs. PARTICIPANTS: 16 students with special needs used K-3000
      (assistive software that provides students with reading support) for six months
      to read assignments for their English language arts class and six teachers who
      had previous experience with integrating K-3000 into their classes were
      recruited. METHODS: Data from focus group interviews of students and teachers
      were used. The advantages and disadvantages of K-3000, the factors that affected
      teachers' use of CBI and users' progress were explored. RESULTS: After the
      regular use of K-3000, students and teachers reported improvement in the amount
      and speed of reading and increased academic self-perception, specifically related
      to reading comprehension and pronunciation. Teachers reported that lack of
      accessibility to technology, time constraints, and difficulties with class
      management were the major reasons that hindered CBI use in their classrooms.
      CONCLUSIONS: Student participants noted that CBI was helpful when they were
      engaged in functional activities related to reading and writing. The progress of
      students in self-perception, and the advantages and drawbacks of the K-3000,
      along with the mechanism of users' progression were described and discussed.

PMID- 21099011
TI  - Nurse perceptions of manual patient transfer training: implications for injury.
AB  - OBJECTIVE: The purpose of this study was to evaluate the perceptions of student
      and staff nurses regarding training they received and their confidence in
      performing a variety of common manual patient transfers (MPTs), given that
      inadequate training may have implications for injury risk. PARTICIPANTS: Student
      nurses (n=163) from a mid-sized university and staff nurses (n=33) from a small
      rural hospital in the university's region. METHODS: Participants were surveyed to
      determine which of 19 MPTs they perceived having received training for and had
      greatest confidence performing. RESULTS: The staff nurses perceived being trained
      on four MPTs; the same four they indicated they had the greatest confidence
      performing. However, nursing students were not trained on these MPTs at the local
      university, indicating an apparent disconnect in training practices between the
      academic institution and the workplace. CONCLUSIONS: It is suggested that a
      participatory ergonomics training approach may help to provide student nurses
      more opportunity to practice MPTs and help all nurses reduce work-related
      musculoskeletal injury risk and increase job satisfaction. Increased training
      time may also allow student nurses to gain greater mastery and confidence of
      skills prior to full-time employment.

PMID- 21099012
TI  - Rural-to-urban male migrant workers' vulnerability to HIV infection in Chengdu,
      China: qualitative findings from a mixed-method study.
AB  - OBJECTIVE: This paper aimed to assess rural-to-urban male migrant workers' HIV
      vulnerability and prevention needs in a Chinese context, specifically in the city
      of Chengdu, capital of the south-western province of Sichuan. PARTICIPANTS: The
      primary sample group were 23 male migrant workers recruited from textile
      factories and construction sites. In addition, a total of 16 key informants
      (e.g., factory managers, healthcare providers and policy makers) and seven
      community members participated in the qualitative phase. METHODS: Qualitative
      methods included semi-structured interviews with male migrant workers and key
      informants, focus group discussions with migrant workers and local community
      members, observation, and review of key policy and programmatic documents related
      to HIV prevention and/or migrant workers. RESULTS: Findings highlight migrant
      workers' vulnerability to HIV for a variety of reasons. Their migrant status
      rendered them economically marginalised and socially isolated. HIV knowledge was
      poor and discriminatory attitudes towards infected people commonplace.
      Perceptions of personal HIV risk were low, even though study participants
      reportedly engaged in sexual behaviours that placed them at risk of infection.
      CONCLUSIONS: A number of interrelated factors contributed to male rural-to-urban
      migrant workers' vulnerability to HIV infection. Targeted HIV prevention programs
      for male migrant workers in Chengdu are urgently needed.

PMID- 21099013
TI  - Isometric strength assessment, Part II: Static testing does not accurately
      classify validity of effort.
AB  - OBJECTIVE: The purpose of this study was to determine if these two commonly
      administered isometric tests are accurate indices of effort. PARTICIPANTS: 34
      healthy subjects were tested once giving a maximum voluntary effort and once
      attempting to feign weakness of 50% of maximum. RESULTS: During feigned weakness
      sessions, 20 of 34 subjects (58.5%), produced CVs of 15% or less during the Leg
      Lift. At the 95% CI, the expected frequency of false negatives for feigned
      weakness is 42.3 to 75.3% for the Leg Lift. At the 95% CI, the expected frequency
      of false negatives for feigned weakness is 51.9% to 83.3% for the Arm Lift.
      CONCLUSIONS: Neither isometric lift is appropriate for classifying validity of
      effort. Use of these isometric lifts should be discontinued for the assessment of
      effort.

PMID- 21099014
TI  - Simultaneous bilateral hand strength testing in a client population, Part II:
      Relationship to a distraction-based lifting evaluation.
AB  - OBJECTIVE: To determine if passing or failing statistically-based validity
      criteria during a distraction-based hand strength assessment is related to test
      behavior during a lifting assessment. PARTICIPANTS: 200 consecutive clients
      presenting for an FCE. METHODS: The two testing protocols, one involving a hand
      strength assessment, the other involving an assessment of lifting capacities,
      were administered to assess the variability between repeated measures. RESULTS:
      Clients failing two or more statistically-based hand strength validity criteria
      had significantly more variability between repeated measures in the lifting
      assessment, p=0.001 and 0.014 for right and left unilateral lifts, respectively,
      and p<0.0005 for three different bilateral lifts. CONCLUSIONS: A pattern of
      performance related to the degree of variability in repeated measures protocols
      for these two distraction-based protocols is revealed. Passing or failing the
      hand strength assessment are each equally predictive of test outcome during the
      distraction-based lifting assessment. The failure of the validity criteria in
      these two distraction-based tests cannot be attributed to a history of surgery
      but, rather, is the result of abnormal test behavior.

PMID- 21099015
TI  - Sources of variation in work disability assessment.
AB  - The assessment of work disability due to health problems is a difficult task
      because there is no straightforward relationship between disease and disability.
      As a result, there is wide inter-rater variability between physicians in
      assessing work disability. The aim of this paper is to discuss the sources of the
      inter-rater variability and to describe possibilities for its reduction. A model
      is presented in which the process of disability assessment, the instruments used
      and the role of the assessor is addressed. On the basis of this model, the causes
      of inter-rater variability and suggestions for improvement are discussed.

PMID- 21099016
TI  - A comparison of two interventions designed to promote neutral wrist postures
      during simple computer operations.
AB  - OBJECTIVE: To compare two postural interventions, a wrist splint and a Wrist
      Alignment Device (WAD) with a biofeedback mechanism. PARTICIPANTS: Nine right
      handed healthy individuals participated in the study. METHODS: Using both hands
      independently a 30-minute office-activity-experiment was performed that consisted
      of data entry, mouse clicking, text dragging, and mouse scrolling executed one
      after the other. Joint motion, tendon travel and productivity levels were
      measured. Participants wore a custom-made flexible electrogoniometric glove (FEG)
      as three scenarios were tested; namely FEG-only, FEG-Splint, and FEG-WAD. Data
      analysis was performed using descriptive statistics and ANOVA. RESULTS: The joint
      motion results produced insignificant differences (p>0.05) between hands. Both
      hands showed larger overall tendon travel for the FEG-only when compared with
      either FEG-Splint or FEG-WAD experiments. Wearing the splint reduced the overall
      tendon travel by 24% and 10% for the left and right hands while using the WAD
      further reduced the overall tendon travel for the left and right hands by 51% and
      42%. Productivity levels were similar across participants with respect to
      experiment task and type. CONCLUSION: The WAD intervention is the most suitable
      device to promote a comfortable and non-restrictive neutral wrist posture.

PMID- 21099017
TI  - The influence of work and treatment related factors on clinical status and
      disability in patients with non-specific work-related upper limb disorders.
AB  - OBJECTIVE: To assess the influence of work- and treatment-related factors on
      clinical status and functional disability in patients with non-specific work
      related upper limb disorders (WRULD). PARTICIPANTS: 182 computer workers with non
      specific WRULD, 18-50 years old, not having specific WRULD nor incomplete medical
      records. METHODS: Retrospective cohort study among computer workers with non
      specific WRULD; average follow-up 4 years. Medical records at time of diagnosis
      and during treatment period and a follow-up questionnaire were used. SETTING:
      Outpatient department of Rehabilitation Medicine, University Hospital Maastricht.
      OUTCOME MEASURES: Non-specific WRULD (clinical status) and Disabilities of Arm,
      Shoulder and Hand (DASH) at follow-up. RESULTS: 103 patients (57%) returned the
      questionnaire. Of these, 14% developed a chronic pain syndrome, 9% recovered, 77%
      worsened slightly. None of the selected work- and treatment-related factors were
      significantly associated with clinical status. "Number of working hours per week
      before diagnosis" was negatively (b=-0.66, p=0.00) and "other therapies during
      treatment" (b=8.76, p=0.02) positively associated with DASH. CONCLUSIONS:
      Computer workers with non-specific WRULD have a poor prognosis. Working more
      hours before diagnosis seems not predictive for disability while having undergone
      other therapies during treatment period does. Prospective cohort studies are
      recommended to unravel the associations found.

PMID- 21099018
TI  - The Booster Break program: description and feasibility test of a worksite
      physical activity daily practice.
AB  - OBJECTIVE: Work breaks are underutilized opportunities to promote health. The
      Booster Break program is a co-worker led physical activity group session devoted
      exclusively to standard 15-minute work breaks. The purpose of this study was to
      report the fidelity, attendance, feasibility, and sustainability of the Booster
      Break program and to explore its potential impact. PARTICIPANTS: The study site
      was a small business that provides legal and court reporting services to lawyers.
      The company's services include legal videography, litigation, records retrieval,
      and videoconferencing to civil attorneys. Established in 1973, the organization
      has 14 employees (8 women and 6 men), from 32 to 66 years of age. METHODS: For
      six months, this small business implemented the Booster Break program. Booster
      Break facilitators conducted the group sessions according to protocol, which
      included describing, cueing, and executing the physical activity sequence.
      RESULTS: During the six month period, 117 sessions were conducted. The average
      monthly attendance ranged from 76% to 86%. Participants significantly improved
      HDL cholesterol (p=0.04) and lost an average of 14 pounds. CONCLUSIONS: The
      Booster Break program is a feasible physical activity program for small business
      settings. The implications of the Booster Break program for future research in
      worksite settings are discussed.

PMID- 21099019
TI  - User-centered design and evaluation of a next generation fixed-split ergonomic
      keyboard.
AB  - OBJECTIVE: Research has shown that fixed-split, ergonomic keyboards lessen the
      pain and functional status in symptomatic individuals as well as reduce the
      likelihood of developing musculoskeletal disorders in asymptomatic typists over
      extended use. The goal of this study was to evaluate design features to determine
      whether the current fixed-split ergonomic keyboard design could be improved.
      PARTICIPANTS: Thirty-nine, adult-aged, fixed-split ergonomic keyboard users were
      recruited to participate in one of three studies. METHODS: First utilizing non
      functional models and later a functional prototype, three studies evaluated
      keyboard design features including: 1) keyboard lateral inclination, 2) wrist
      rest height, 3) keyboard slope, and 4) curved "gull-wing" key layouts. RESULTS:
      The findings indicated that keyboard lateral inclination could be increased from
      8 degrees  to 14 degrees ; wrist rest height could be increased up to 10 mm from
      current setting; positive, flat, and negative slope settings were equally
      preferred and facilitated greater postural variation; and participants preferred
      a new gull-wing key layout. The design changes reduced forearm pronation and
      wrist extension while not adversely affecting typing performance. CONCLUSIONS:
      This research demonstrated how iterative-evaluative, user-centered research
      methods can be utilized to improve a product's design such as a fixed-split
      ergonomic keyboard.

PMID- 21099020
TI  - Determination of the crystal structure of magnesium perchlorate hydrates by X-ray
      powder diffraction and the charge-flipping method.
AB  - X-ray powder diffraction (XRD) data were used to solve the crystal structures of
      phases in the magnesium perchlorate hydrate system, Mg(ClO(4))(2).nH(2)O (n = 4,
      2). A heating stage and humidity generator interfaced to an environmental cell
      enabled in-situ XRD analyses of dehydration reactions under controlled
      temperatures and partial pressures of H(2)O (P(H(2)O)). The crystal structures
      were determined using an ab initio charge-flipping method and were refined using
      fundamental-parameter Rietveld methods. Dehydration of magnesium perchlorate
      hexahydrate to tetrahydrate (348 K) results in a decrease in symmetry (space
      group = C2), where isolated Mg(2+) cations are equatorially coordinated by four
      H(2)O molecules with two [ClO(4)](-) tetrahedra at the apices. Further
      dehydration to the dihydrate (423 K) leads to bridging of the isolated packets to
      form double corner-sharing chains of octahedra and polyhedra (space group =
      C2/m).

PMID- 21099021
TI  - The modulated structure of the calcium aluminate Ca6(AlO2)12.Bi2O3.
AB  - Bismuth calcium aluminate, Bi(2)Ca(6)Al(12)O(27), has been prepared as a ceramic
      and a single crystal. Analysis of reciprocal space using both electron and X-ray
      diffraction show an R-centred hexagonal unit cell: a = b = 17.3892 (4), c = 6.986
      (1) A. Additional weak reflections are observed; they require the introduction of
      a modulation wavevector q = 0.0453 (2)c* for indexing. The modulated structure
      has been solved using the superspace formalism [superspace group X3(00gamma)0]. A
      framework of corner-sharing AlO(4) tetrahedra forms corrugated sixfold rings and
      uncommon triple rings. The Ca(2+) cations exhibit an eightfold coordination
      sphere; edge-sharing CaO(8) polyhedra form intertwinned zigzagging rows along c
      creating a three-dimensional net. Bi atoms are located in large hexagonal tunnels
      parallel to c and form Bi(2)O(3) pairs, which adopt a trigonal bipyramidal
      configuration. The 6s(2) lone-electron pairs (Lp) point along c, in the opposite
      direction to the three Bi-O strong bonds to form two BiO(3)Lp tetrahedra with a
      common base. Different orientations of the Bi(2)O(3)Lp(2) pairs, rotated by 60
      degrees  around c, are observed. Their stacking modes in each of the hexagonal
      tunnels are described. The sequence of the stacking varies along c in each of the
      tunnels.

PMID- 21099022
TI  - Structure and electrical properties of the new pyrochlore-type protonic solid
      electrolyte K(0.88)Nb2O(7.58)H(4.28).
AB  - Single-crystal, synchrotron powder X-ray diffraction and neutron powder
      diffraction studies of the novel pyrochlore-type compound with the structural
      formula K(0.88)(OH)(0.54)H(1.66)(H(2)O)(1.04)Nb(2)O(6) suggests that the water
      molecules are located in 32e sites, and the hydroxide ions and potassium ions are
      located in 16d sites with a significant amount of 'free' protons in 96g sites.
      The total weight loss at temperatures up to 773 K is only about 8%, suggesting
      the oxygen escape from 48f sites can be excluded and 'free' protons must be
      preserved in the structure. The bulk conductivity in ambient air reaches 10(-2) S
      cm(-1) at 623 K. Owing to the extended stability range and resistance to water
      solubility, the compound can be considered as a candidate for intermediate
      temperature solid-oxide fuel-cell applications.

PMID- 21099023
TI  - Crystal chemistry of transition metal diarsenates M2As2O7 (M = Mn, Co, Ni, Zn):
      variants of the thortveitite structure.
AB  - The structures of the 3d divalent transition-metal diarsenates M(2)As(2)O(7) (M =
      Mn, Co, Ni, Zn) can be considered as variants of the monoclinic (C2/m)
      thortveitite [Sc(2)Si(2)O(7)] structure type with a ? 6.7, b ? 8.5, c ? 4.7 A,
      alpha ? 90, beta ? 102, gamma ? 90 degrees  and Z = 2. Co(2)As(2)O(7) and
      Ni(2)As(2)O(7) are dimorphic. Their high-temperature (beta) polymorphs adopt the
      thortveitite aristotype structure in C2/m, whereas their low-temperature (alpha)
      polymorphs are hettotypes and crystallize with larger unit cells in the triclinic
      crystal system in space groups P?bar 1 and P1, respectively. Mn(2)As(2)O(7)
      undergoes no phase transition and likewise adopts the thortveitite structure type
      in C2/m. Zn(2)As(2)O(7) has an incommensurately modulated crystal structure
      [C2/m(alpha,0,gamma)0s] with q = [0.3190 (1), 0, 0.3717 (1)] at ambient
      conditions and transforms reversibly to a commensurately modulated structure with
      Z = 12 (I2/c) below 273 K. The Zn phase resembles the structures and phase
      transitions of Cr(2)P(2)O(7). Besides descriptions of the low-temperature
      Co(2)As(2)O(7), Ni(2)As(2)O(7) and Zn(2)As(2)O(7) structures as five-, three- and
      sixfold superstructures of the thortveitite-type basic structure, the superspace
      approach can also be applied to descriptions of all the commensurate structures.
      In addition to the ternary M(2)As(2)O(7) phases, the quaternary phase
      (Ni,Co)(2)As(2)O(7) was prepared and structurally characterized. In contrast to
      the previously published crystal structure of the mineral petewilliamsite, which
      has the same idealized formula and has been described as a 15-fold superstructure
      of the thortveitite-type basic structure in space group C2, synthetic
      (Ni,Co)(2)As(2)O(7) can be considered as a solid solution adopting the alpha
      Ni(2)As(2)O(7) structure type. Differences of the two structure models for
      (Ni,Co)(2)As(2)O(7) are discussed.

PMID- 21099024
TI  - Structure of N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)toluenesulfonamide by combined X
      ray powder diffraction, 13C solid-state NMR and molecular modelling.
AB  - The crystal structure solution of the title compound is determined from
      microcrystalline powder using a multi-technique approach that combines X-ray
      powder diffraction (XRPD) data analysis based on direct-space methods with
      information from (13)C solid-state NMR (SSNMR), and molecular modelling using the
      GIPAW (gauge including projector augmented-wave) method. The space group is Pbca
      with one molecule in the asymmetric unit. The proposed methodology proves very
      useful for unambiguously characterizing the supramolecular arrangement adopted by
      the N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)toluenesulfonamide molecules in the
      crystal, which consists of extended double strands held together by C-H...pi non
      covalent interactions.

PMID- 21099025
TI  - Thermal motion of tert-butyl groups III. tert-Butyl substituents in aromatic
      hydrocarbons, the view from the bottom of the well.
AB  - The rigidity of the tert-butyl group (TBG) as a substituent in aromatic
      hydrocarbons is investigated, with a modified Hirshfeld test of anisotropic
      displacement parameters (ADPs) as a primary criterion. Four new structures are
      analyzed, along with low-temperature studies of a previously published crowded
      supermesityl dimer; three of the five structures meet the primary test. Most of
      the TBGs meet the Hirshfeld test at 100 K, and the ADPs are improved by omitting
      low-order data in the final refinement. The three most precise structures yield a
      wide variation in libration amplitudes (and in estimated rotation barriers) for
      13 unique TBGs. A similar range of values is found in analyses of structures in
      the Cambridge Crystallographic Database. The libration amplitudes are calculated
      with the program THMA14C, with each TBG as an attached rigid group (ARG). Packing
      analysis suggests that large ADPs, especially for some individual TBG methyl
      groups, correspond to voids in the crystal. Published barriers to TBG
      reorientation, determined by solid-state NMR spin-lattice relaxation methods, for
      six related crystalline compounds are compared with barriers calculated from
      their crystal structure data.

PMID- 21099026
TI  - Direct observation of arylnitrene formation in the photoreaction of arylazide
      crystals.
AB  - Seven crystal structures of arylazides, 2-azidobiphenyl (2), 4-(4
      azidophenyl)butanoic acid (3), 3-azidobenzoic acid (4), N-(4
      azidophenyl)acetamide (5), 2,4,6-trichlorophenyl azide (6), 2,5-dibromophenyl
      azide (7) and 2,4,6-tribromophenyl azide (8), have been analyzed by X-rays. When
      the crystals were irradiated with UV light at ? 80 K, only 2-azidobiphenyl
      gradually changed its cell dimensions with the retention of the single-crystal
      form. The crystal structure after photo-irradiation was analyzed by X-rays under
      the same conditions as those before photo-irradiation. Approximately 20% of the 2
      azidobiphenyl molecule was converted to the triplet 2-biphenylnitrene and
      dinitrogen molecules. The existence of the triplet nitrene was confirmed by ESR
      and IR measurements. Although the structure of dinitrogen was clearly determined,
      the nitrene structure was obscure because the nitrene produced was almost
      superimposed on the original 2-azidobiphenyl. The other six crystals were non
      reactive or easily broken when they were exposed to UV light. The different
      reactivity between 2-azidobiphenyl and the other compounds was successfully
      explained by the reaction cavity of the azido group.

PMID- 21099027
TI  - Direct observation of various reaction pathways of arylnitrenes in different
      crystal environments caused by acid-base complex formation.
AB  - The structures of reaction intermediates, arylnitrenes and their final products
      have been successfully analyzed by X-rays using acid-base complex formation. The
      acid-base complexes of 2-azidobenzoic acid (2a), 3-azidobenzoic acid (3a) and 4
      azidobenzoic acid (4a) were made with dibenzylamine (db), N-benzyl-2
      phenylethylamine (bp) and dicyclohexylamine (dc). For the complex crystals of
      (3a) and db (3a-db), and (4a) and db (4a-db) two forms of (I) and (II) were
      obtained. Eight types of complex crystals, (2a-db), (3a-db-I), (3a-db-II), (3a
      dc), (4a-db-I), (4a-db-II), (4a-bp) and (4a-dc), suitable for X-ray analysis were
      obtained. When the crystals were irradiated with UV light at low temperatures,
      the reactions proceeded keeping the single-crystal form in the five crystals (2a
      db), (3a-db-I), (3a-db-II), (3a-dc) and (4a-bp). Less than 25% of each
      azidobenzoic acids was transformed into an arylnitrene and dinitrogen. In three
      crystals the arylnitrenes produced gave new final products; 2,1-benzisoxazolone
      was observed for (2a-db) and trans-azobenzenes (i.e. dimerized nitrenes) were
      obtained for (3a-db-II) and (4a-bp). For (3a-db-I) and (3a-dc) the intermediate
      arylnitrenes were observed but did not transform to new products. All the
      structural changes were directly observed by X-ray analysis because the
      incomplete reactions occurred with retention crystallinity. The crystal
      environment, including the hydrogen bonding between the benzoic acid and the
      amine, places restrictions on the movement of the arylnitrene and influences the
      reaction pathway followed for conversion of the arylnitrene to its final product.

PMID- 21099028
TI  - Structures of cyclic dipeptides: an X-ray and computational study of cis- and
      trans-cyclo(Pip-Phe), cyclo(Pro-Phe) and their N-methyl derivatives.
AB  - The crystal structures of eight cyclodipeptides are determined, incorporating
      pipecolic acid or proline and phenylalanine or N-methyl phenylalanine. This set
      of structures allows the evaluation of the effects on molecular conformation and
      crystal packing of imino acid ring-size, relative configuration of the two amino
      acids, and N-methylation. In the non-methylated compounds, hydrogen-bonding
      interactions form one-dimensional motifs that dominate the packing arrangement.
      Three compounds have more than one symmetry-independent molecule in the
      asymmetric unit (Z' > 1), indicative of a broad and shallow molecular energy
      minimum. Density functional theory calculations reveal the interplay between
      inter- and intramolecular factors in the crystals. Only for the N-methylated
      compounds do simulations of the molecules in the isolated state succeed to
      reproduce the observed crystallographic conformations. Puckering of the
      diketopiperazine ring and the deviation from planarity of the amide bonds are not
      reproduced in the remaining compounds. Cluster in vacuo calculations with a
      central cyclodipeptide molecule surrounded by hydrogen-bound molecules establish
      that hydrogen bonding is of major importance but that other intermolecular
      interactions must also contribute substantially to the crystal structure. More
      advanced periodic calculations, incorporating the crystallographic environment to
      the full extent, are necessary to correctly describe all the conformational
      features of these cyclodipeptide crystals.

PMID- 21099029
TI  - Solid solution of two diastereomers of [3a(R,S),7a(R,S)]-3-[(1'R)-1
      phenylethyl]perhydro-1,3-benzothiazol-2-iminium chloride.
AB  - A mixture of two diastereomers with the configurations (3aS,7aS,1'R) and
      (3aR,7aR,1'R) forms co-crystals in which there is one unique molecule in the
      asymmetric unit, but the molecule displays disorder which is a result of the
      presence of the two diastereomers at the same crystallographic site. Theoretical
      calculations carried out by the DFT method with the 6-311++G(2df,p) basis set
      allowed for the estimation of the energy difference between the two diastereomers
      both in the isolated and the solid state, while the natural bond orbital (NBO),
      Mulliken, natural population (NPA) and CHelpG analyses helped to establish the
      electronic structure of the thazolidin-2-imine fragment.

PMID- 21099030
TI  - Electron density studies on hydrogen bonding in two chromone derivatives.
AB  - The experimental electron densities of two chromone derivatives have been
      determined from X-ray synchrotron diffraction data at low temperature (100 K).
      Topological analysis of the electron density has been used to analyze the
      formation of resonance-assisted hydrogen bonds (RAHBs). Geometrical and
      topological parameters confirm pi-electron delocalization within the hydrogen
      bonded ring. In addition, weak C-H...O interactions were identified in both
      structures. Hydrogen-bond energies allowed medium and weak hydrogen bonds to be
      distinguished.

PMID- 21099031
TI  - Diffuse scattering study of aspirin forms (I) and (II).
AB  - Full three-dimensional diffuse scattering data have been recorded for both
      polymorphic forms [(I) and (II)] of aspirin and these data have been analysed
      using Monte Carlo computer modelling. The observed scattering in form (I) is well
      reproduced by a simple harmonic model of thermally induced displacements. The
      data for form (II) show, in addition to thermal diffuse scattering (TDS) similar
      to that in form (I), diffuse streaks originating from stacking fault-like defects
      as well as other effects that can be attributed to strain induced by these
      defects. The present study has provided strong evidence that the aspirin form
      (II) structure is a true polymorph with a structure quite distinct from that of
      form (I). The diffuse scattering evidence presented shows that crystals of form
      (II) are essentially composed of large single domains of the form (II) lattice
      with a relatively small volume fraction of intrinsic planar defects or faults
      comprising misoriented bilayers of molecular dimers. There is evidence of some
      local aggregation of these defect bilayers to form small included regions of the
      form (I) structure. Evidence is also presented that shows that the strain effects
      arise from the mismatch of molecular packing between the defect region and the
      surrounding form (II) lattice. This occurs at the edges of the planar defects in
      the b direction only.

PMID- 21099032
TI  - Characteristics of DOC concentration with storm density flows in a stratified dam
      reservoir.
AB  - Among natural organic matter (NOM) defined as the complex matrix of organic
      materials abundant in natural waters, a gradual accumulation of recalcitrant
      organic matter (ROM) has been observed in impounded water bodies such as a lake
      or dam reservoir in spite of extensive efforts made to curtail organic pollutant
      loadings generated in their catchment areas. This paper aims to identify the
      effect of diffuse pollution resulting from allochthonous organic matters on the
      temporal and spatial characteristics of organic matters in a stratified dam
      reservoir, Daecheong Dam, using both intensive observation and CE-QUAL-W2 model
      simulation. With the limitation of observation data in terms of organic matters
      of inflow waters from boundary tributaries and impounded water in the reservoir,
      organic matter was represented by organic carbon including labile particular
      organic carbon (LPOC), refractory organic carbon (RPOC), labile dissolved organic
      carbon (LDOC), and refractory organic carbon (RDOC). Both autochthonous and
      allochthonous origins of organic carbon were considered in the modeling of
      eutrophication of the reservoir water using CE-QUAL-W2. The result of simulation
      during the period from 2001 to 2005 was observed to be a gradual accumulation of
      particular organic carbon (POC). It is clear that the model calculation results
      enable the explanation of the internal and external movement of constituents in
      the reservoir. In particular turbidity and NOM were well related in the upper
      region of the reservoir according to flow distance, gradually changing to
      dissolved form of organic matter, DOC affected organic matter concentration of
      reservoir water quality compared to turbidity.

PMID- 21099033
TI  - Integrated approach for biofouling control.
AB  - Despite extensive research efforts, past and present strategies to control
      biofouling problems in spiral-wound nanofiltration and reverse osmosis membranes
      have not been successful under all circumstances. Gaining insight in the
      biofouling process is a first necessity. Based on recent insights, an overview is
      given of 12 potential complementary approaches to solve biofouling. Combinations
      of approaches may be more efficient in biofouling control than a single approach.
      A single approach must be 100% effective, while in combination each individual
      approach can be partially effective while the combination is still efficient. An
      integrated Approach for Biofouling Control (ABC) is proposed, based on three
      corner stones: (i) equipment design and operation, (ii) biomass growth
      conditions, and (iii) cleaning agents as a framework to control biofouling. While
      past and present strategies addressed mainly membranes and microorganisms, i.e.
      removal or inactivation of biomass, this ABC-approach addresses the total
      membrane filtration system. It is anticipated that this integral approach will
      enable a more rational and effective control of biofouling. Although in this
      stage chemical cleaning and biofouling inhibitor dosage seem unavoidable to
      control biofouling, it is expected that in future--because of sustainability and
      costs reasons--membrane systems will be developed without or with minimal need
      for chemical cleaning and dosing. Three potential scenarios for biofouling
      control are proposed based on (i) biofouling tolerant spiral wound membrane
      systems, (ii) capillary membranes, and (iii) phosphate limitation.

PMID- 21099035
TI  - Analysis and occurrence of typical endocrine-disrupting chemicals in three sewage
      treatment plants.
AB  - Seven typical endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA),
      4-tert-octylphenol (OP), estrone (E1), estradiol (E2), 17alpha-estradiol (17alpha
      E2), estriol (E3) and 17alpha-ethinylestradiol (EE2) in wastewater, were
      simultaneously determined with gas chromatography-mass spectrometry (GC-MS).
      Samples, including influents, effluents and wastewater of different unit
      processes, were taken seasonally from three different sewage treatment plants.
      The result showed that BPA and EE2 were the two main types of EDCs in all the
      samples. The average concentration of BPA were in the range of 268.1-2,588.5 ng l
      1 in influents and 34.0-3,099.6 ng l-1 in effluents, while EE2 ranging from 133.1
      to 403.2 ng l-1 and from 35.3 to 269.1 ng l-1, respectively. Seasonal change of
      EDCs levels in effluents was obvious between wet season and dry season. Besides,
      BPA and E3 could be effectively removed by the biological treatment processes
      (oxidation ditch and A2/O) with the unit removal of 64-91% and 63-100% for each
      compound, while other five EDCs had moderate or low removal rates. The study also
      proved that physical treatment processes, including screening, primary
      sedimentation and pure aeration, had no or little effect on EDCs removal.

PMID- 21099034
TI  - Activated bauxite waste as an adsorbent for removal of Acid Blue 92 from aqueous
      solutions.
AB  - Bauxite waste, known as red mud, is produced in some industrial processes, such
      as aluminum production process. In this process, the waste material is produced
      from leached bauxite as a by product. In this research, the removal of Acid Blue
      92 (AB92) dye was investigated from aqueous solution onto the activated bauxite
      waste (red mud) in a batch equilibration system. Besides, the influences of pH,
      adsorbent dosage, contact time, initial concentration of dye and temperature have
      been considered. It was found that the OH group is an effective functional group
      for the adsorption process. The intensity of the peaks correspond to OH group has
      been significantly climbed after the activation process. The adsorption kinetics
      of AB92 can be well described by the pseudo-second-order reaction model. Based on
      the isotherm data obtained from the fittings of the adsorption kinetics, the
      Langmuir model appears to fit the adsorption process better than the Freundlich
      and Brunauer-Emmett-Teller (BET) models.

PMID- 21099036
TI  - A polyvinylchloride-based cadmium ion-selective electrode using [Mo2(OAc)2(H2
      calix[4]arene)] as an electroactive material.
AB  - A highly electroactive material [Mo2(OAc)2(H2-calix[4]arene)] is used as a
      neutral carrier for Cd2+ ions in this paper. The membrane is fabricated by using
      ionophore [Mo2(OAc)2(H2-calix[4]arene)]:poly(vinyl chloride) (PVC):
      dibutylphthalate(DBP):sodium tetraphenyl borate (NaTPB) in the ratio of
      40:300:470:5 respectively and tetrahydrofuran (THF) used as a solvent. The
      membrane electrode performed in the concentration range of 9.9 x 10-8-1.0 x 10-1
      M (2.34 x 10-5-23.64 mg/mL) having the Nernstian slope of 30.0+/-1.0 mV and the
      best detection limit was observed at 9.8 x 10-8 M (2.31 x 10-5 mg/mL). The
      proposed membrane electrode has the response time of 12 s and a useful working pH
      range of 1.0-7.0, and used over a period of 10 months and work satisfactorily in
      the test solution having 30% (v/v) non-aqueous content. Electrode sensor has
      distinguishable ability for Cd2+ ion with regard to several alkali, alkaline
      earth, transition and heavy metal ions. It was used in direct potentiometry as an
      indicator electrode, in the potentiometric titration of 10-3 M Cd2+ solution
      against 10-2 M of ethylenediaminetetraacetic acid (EDTA).

PMID- 21099037
TI  - Effect of glucose on enzyme activity and color removal by Trametes versicolor for
      high strength landfill leachate.
AB  - This research was carried out to study the treatment of landfill leachate by
      immobilized Trametes versicolor BCC 8725. Leachate was collected from Nonthaburi
      disposal site of Thailand from a pipe as discharged from landfill to the
      stabilization pond. Batch experiments were conducted to determine the effects of
      carbon source (glucose) on the biomass growth of fungi and the treatment of
      leachate in terms of color, Biological Oxygen Demand (BOD) and Chemical Oxygen
      Demand (COD) removal. Enzymes produced by Trametes versicolor BCC 8725 were also
      analyzed. Experimental results indicated a higher biomass growth when glucose was
      added, indicating that the growth of fungi is dependent on the co-substrate. The
      percentage of color removal is approximately 58% and 12%, respectively, with and
      without glucose. BOD and COD removals were 37% and 40% with glucose addition
      within 12 days at optimum conditions. Enzyme analysis indicated that laccase was
      the main enzyme produced. In addition, Manganese Peroxidase (MnP) and Lignin
      Peroxidase (LiP) were also detected. The fungi were able to produce the enzymes.
      The peak concentrations of LiP, MnP and laccase activity were found to be 384,
      1,241, 2,534 unit/litre (U/L) with glucose, indicating that the color removal
      rates were proportional to the enzyme activity.

PMID- 21099038
TI  - Treatment of thermomechanical pulping condensate using thermophilic and
      mesophilic sequencing batch reactors.
AB  - In-mill thermophilic treatment of individual wastewater streams to achieve water
      system closure has received much attention in pulp and paper mills. Aerobic
      biological treatment of thermomechanical pulping (TMP) condensate was conducted
      using thermophilic (55  degrees C) and mesophilic (35  degrees C) sequencing
      batch reactors (SBRs) for a period of 143 days at a cyclic time of 6, 8 and 12 h.
      A soluble chemical oxygen demand (SCOD) removal efficiency of 77 to 91% was
      achieved, given an organic loading rate of 0.7-1.3 kg/m3 d. The COD removal
      efficiency of the thermophilic SBR was slightly lower than that of the mesophilic
      SBR. Majority of the soluble COD was removed by biodegradation with a small
      portion (9-13%) of soluble COD stripped by aeration. The settleability (sludge
      volume index) and the flocculating ability (effluent suspended solids) of
      thermophilic sludge were comparable to or slightly poorer than that of the
      mesophilic sludge. The level of filaments in thermophilic sludge was usually
      higher than that in mesophilic sludge. The results of the study indicate that
      both thermophilic and mesophilic SBRs can be successfully operated for in-mill
      treatment of TMP condensate. The treated effluent has the potential for
      subsequent reuse in the mill.

PMID- 21099039
TI  - Economic analyses for optimizing the construction of separate sewer in a hybrid
      sewer system.
AB  - Metropolitan Taipei located in north Taiwan uses a hybrid sewer system consisting
      of mostly separate sewer for the populated regions, and partly combined sewer for
      less populated regions. This study used the concept that Marginal Cost of Control
      (MCC) equals to Marginal Benefits of Control (MBC) to establish the method for
      studying the optimal household connection percentage, and the most cost-effective
      construction of the separate sewer in the hybrid sewer system. Results indicate
      the improvement of the receiving water quality in a cost-effective analysis
      manner. The most cost-effective sanitary sewer construction can be reached when
      the stream Biochemical Oxygen Demand (BOD5) meets the river quality standard,
      which can be applied in other cities and existing systems.

PMID- 21099040
TI  - A modified culture-based study of bacterial community composition in a tannery
      wastewater treatment plant.
AB  - Though culture-independent methods have been used in preference to traditional
      isolation techniques for characterization of microbial community of wastewater
      treatment plants, it is difficult to widely apply this approach in resource-poor
      countries. The present study aimed to develop a test to identify the culturable
      portion of bacterial community in a high-strength wastewater. Wastewater samples
      were collected from nitrification-denitrification and settling tanks of the
      treatment plant of Elmo Leather AB tannery located in Boras, Sweden. After
      cultivating on nutrient agar with the optimal dilution (10-2), phenotypic and
      biochemical identification of the bacteria were done with colony morphology, Gram
      reaction, growth on MacConkey, phenylethanol media, triple sugar Iron agar
      slants, catalase and oxidase tests. Biochemical grouping of the isolates was done
      based on their test results for MacConkey, phenylethanol media, triple sugar Iron
      agar and oxidase test reaction. From the biochemical groups, isolates were
      randomly selected for API test and 16SrRNA gene sequencing. The isolates from the
      denitrification, nitrification tank were identified to be Paracoccus
      denitrificans (67%), Azoarcus spp (3%) and Spingomonas wittichii (1%). From the
      settling tank, Paracoccus denitrificans (22%), Corynebacterium freneyi (20%) and
      Bacillus cereus (1%) were identified. The grouping based on biochemical test
      results as well as the identification based on sequencing has shown coherence
      except for discrepancies with the API test. The preliminary implications of the
      grouping based on culture-based characteristics and its potential application for
      resource-limited environmental microbial studies is discussed.

PMID- 21099041
TI  - Source of N-nitrosodimethylamine in river waters of the upper Tone River basin in
      Japan.
AB  - The presence of N-nitrosodimethylamine (NDMA) in the Hirose River and its
      tributaries, located in the upper Tone River basin, in the Kanto region of Japan,
      was investigated. NDMA was detected at high levels in the Arato River, one of the
      tributaries of the Hirose River, at high concentrations (up to 2,100 ng/L). Due
      to the confluence of the Arato River, NDMA concentration in the Hirose River
      increased (up to 61 ng/L). The NDMA in the Arato River was due to industrial
      discharge from a livestock processing plant located near the river. There were
      three discharges at the plant, with NDMA concentrations of 78, 11, and 33,000
      ng/L. The industrial discharges from the livestock processing plant did not
      contain significant amounts of NDMA precursors on chloramination. On the other
      hand, sewage effluent was shown to contain NDMA precursors. The amounts of NDMA
      precursors in the sewage effluent that were rapidly transformed into NDMA were
      considered to be lower than those slowly transformed into NDMA.

PMID- 21099042
TI  - Evaluation of stormwater BMPs for implementing industrial stormwater permitting
      strategy.
AB  - This study assesses the performance of stormwater best management practices
      (BMPs) in industrial sectors and their effluent quality to facilitate the
      development of technology-based numerical effluent criteria. Generally, retention
      ponds outperform other BMP types for reducing total suspended solids, and media
      filter and wetland basins outperform other BMPs for metal removal. Detention
      basins were not effective in reducing stormwater pollution although they can
      retain the stormwater before entering surface waters. However, many BMPs show
      high variability of influent and effluent concentrations and no significant
      difference between them, which makes it difficult to determine the effectiveness
      of the BMP. In some cases, low influent concentrations govern the distribution of
      effluent concentrations and effluent concentrations are often greater than inflow
      concentrations. The analysis results can be used to assist in the developing a
      watershed based multisector industrial stormwater general permit to ensure
      compliance with total maximum daily loads. The results also suggest the need for
      additional monitoring data.

PMID- 21099043
TI  - Fecal coliform removal in a sulfate reduction, autotrophic denitrification and
      nitrification integrated (SANI) process for saline sewage treatment.
AB  - The Sulfate Reduction, Autotrophic Denitrification, Nitrification Integrated
      (SANI) process has been specially designed to treat saline wastewater. In the
      process no biological excess sludge is produced. SANI process also has the added
      advantages of cost and footprint reduction when compared to traditional activated
      sludge processes. In the SANI pilot plant, the fecal coliform removal efficiency
      in the sulfate reducing up-flow sludge bed (SRUSB) was found to be 1.4 log,
      whereas that in the subsequent anoxic and aerobic reactors it was 0.6 and 0.2
      log, respectively, leading to a relatively high overall coliform removal of 2.2
      log. Sulfide was confirmed to be toxic to fecal coliform and the contact time
      between the sulfide produced and coliform in the SRUSB played an important role
      in the removal.

PMID- 21099044
TI  - Aerobic granule formation in a sequencing batch reactor treating newsprint
      effluent under low phosphate conditions.
AB  - Pulp and paper mills are under increasing pressure to minimize the discharge of
      phosphate to receiving waters. We investigated the operation of two laboratory
      sequencing batch reactors (SBR) under low phosphate conditions over a period of
      eight months. Performance characteristics in terms of COD and TSS removal were
      similar to the full-scale mill activated sludge operation, but the floc density
      and structure was improved. Sludge yield as a result of phosphate limitation was
      routinely lower than 0.15 kg/kg of COD. Aerobic granule formation was established
      in one of the SBRs by reducing the settling time from 30 min to 2 min and by
      increasing stirring shear force. Once established, the brown granules which were
      1-2 mm in diameter were stable over five months of operation. Extracellular
      polymeric substance (EPS) analysis of the granules indicated a higher galactose
      content and lower mannose content than in conventional flocs. The granules
      generated more quorum sensing compound (acyl homoserine lactone) than
      conventional flocs, suggesting that quorum sensing could play a role in granule
      formation. When compared to the conventional SBR, the aerobic granule SBR
      performed at a higher organic loading, at faster settling velocity, and without
      filamentous bulking.

PMID- 21099045
TI  - Sensitivity analysis using a diffuse pollution hydrologic model to assess factors
      affecting pesticide concentrations in river water.
AB  - We quantitatively evaluated the factors that affect the concentrations of rice
      farming pesticides (an herbicide and a fungicide) in river water by a sensitivity
      analysis using a diffuse pollution hydrologic model. Pesticide degradation and
      adsorption in paddy soil affected concentrations of the herbicide pretilachlor
      but did not affect concentrations of the fungicide isoprothiolane. We attributed
      this difference to the timing of pesticide application in relation to irrigation
      and drainage of the rice paddy fields. The herbicide was applied more than a
      month before water drainage of the fields and runoff was gradual over a long
      period of time, whereas the fungicide was applied shortly before drainage and
      runoff was rapid. However, the effects of degradability-in-water on the herbicide
      and fungicide concentrations were similar, with concentrations decreasing only
      when the rate constant of degradation in water was large. We also evaluated the
      effects of intermittent irrigation methods (irrigation/artificial drainage or
      irrigation/percolation) on pesticide concentrations in river water. The runoff of
      the fungicide, which is applied near or in the period of intermittent irrigation,
      notably decreased when the method of irrigation/artificial drainage was changed
      to irrigation/percolation. In a sensitivity analysis evaluating the synergy
      effect of degradation and adsorbability in soil, the degradation rate constant in
      soil greatly affected pesticide concentration when the adsorption coefficient was
      small but did not affect pesticide concentration when the adsorption coefficient
      was large. The pesticide concentration in the river water substantially decreased
      when either or both the degradation rate constant in soil and adsorption
      coefficient was large.

PMID- 21099046
TI  - Integration of nitrification and denitrification by combining anoxic and aerobic
      conditions in a membrane bioreactor.
AB  - A membrane bioreactor (MBR) was developed to achieve nitrogen removal by
      combining nitrification and denitrification conditions in one reactor. The
      activated sludge was alternated between aerobic and anoxic conditions using
      peristaltic pump. The biomass concentration and floc morphological properties
      were observed to be similar in anoxic and aerobic compartments. However, the
      homogeneous properties of the activated sludge did not lead to the failure of
      oxygen gradient formation in the reactor. Due to the position of the air
      diffuser, an anoxic compartment at the bottom and an aerobic compartment in the
      upper part of the reactor were formed after 40 days. The average total nitrogen
      (TN) removal efficiency was then observed to increase to 77%. The microbial
      characterization using polymerase chain reaction-denaturing gradient gel
      electrophoresis (PCR-DGGE) analysis, as well as the specific nitrogen utilization
      rate measurements, indicated that the nitrogen removal in the reactor occurred
      via nitrification and denitrification processes.

PMID- 21099047
TI  - Nitrogen removal from livestock and poultry breeding wastewaters using a novel
      sequencing batch biofilm reactor.
AB  - A study was conducted regarding the biological nitrogen removal from the
      livestock and poultry breeding wastewater (LPBWs) using a novel sequencing batch
      biofilm reactor (SBBR). Nitrogen removal process was studied under three aeration
      strategies/modes, referred to as MODE 1, 2, and 3. The results showed that MODE 2
      (one operation period: instant fill of LPBWs, 3.0 h aeration, 1.5 h non-aeration,
      1.5 h aeration, 1.0 h non-aeration and rapid drain of treated LPBWs) performed
      the best in nitrogen removal. Under MODE 2, the removal efficiencies were as high
      as 96.1 and 92.1% for NH3-N and TN, respectively. Simultaneous nitrification and
      denitrification (SND), as well as shortcut nitrification and denitrification are
      likely to be the two main mechanisms for the nitrogen removal in this study.
      Nitrifying bacteria were not inhibited by heterotrophic bacteria with C/N ratios
      ranging from 18.1 to 21.4 and DO concentration of 2.0 mg/l. Alternation between
      aeration and non-aeration played an important role in NO2- accumulation.

PMID- 21099048
TI  - Relationship between land use and water quality in a small watershed in South
      Korea.
AB  - Recent research and monitoring undertaken by various institutions have emphasized
      measurements of river-water quality. Based on the results, government agencies
      have set guidelines to improve river-water quality management. However, the
      relationship between water quality and land use/land cover (LULC) has not been
      examined closely in South Korea to date. This study investigated this
      relationship in the Imgok River watershed. For this study, the relationship
      between water quality parameters, e.g. metallic ions, biological oxygen demand
      and chemical oxygen demand (BOD and COD), NH3, NO3 and PO4 levels and land-use
      types (abandoned mine land, forest/grassland, agricultural, livestock and
      residential areas) was examined by correlation analysis with significant level
      (p<0.05) and principal component analysis (PCA). Applying PCA to water quality
      parameters according to land-use coverage, the principal component impacting
      river water quality were found to be the pH, metallic ions, BOD, PO4, COD and
      total suspended solids (TSS) for abandoned mine land (AML) coverage; BOD, NO3 and
      PO4 for forest/grassland areas; TSS, NO3, and PO4 for agricultural land; BOD,
      COD, NH3 and NO3 for livestock coverage; and BOD, COD, NH3 and PO4 for
      residential areas. For the AML, the pH exhibited a significant negative
      correlation with other water quality parameters at the significant level
      (p<0.05). Grassland showed significant positive correlations of BOD with values
      of 0.837 NO3 and 0.514 PO4. In agricultural land, TSS had a significant negative
      correlation with value of -0.772 PO4. For livestock coverage, BOD had significant
      positive correlations with values of 0.865 COD, 0.629 NH3, 0.709 NO3 and 0.472
      TSS. In residential areas, COD was significantly positively correlated with
      values of 0.988 BOD and 0.856 PO4, and TSS was highly positively correlated with
      value of 0.810 NO3 but highly negatively correlated with value of -0.702 PO4.
      Based on the above, LULC is a significant factor to influence on river water
      quality and this relationship should be based on the management plan for river
      water quality control. Future work will be conducted to take more samples in the
      entire river and season, to run water quality model and to choose a new method
      for better analysis and more accurate relationship between land-use and water
      quality.

PMID- 21099049
TI  - Viability of Ascaris and other helminth genera non larval eggs in different
      conditions of temperature, lime (pH) and humidity.
AB  - Helminth eggs are the pathogens most resistant to inactivation during sludge and
      wastewater treatment. For this reason, in several regulations and the WHO
      guidelines for wastewater and excreta reuse for agriculture and aquaculture they
      are considered as indicators of the performance of the treatment process.
      Conditions required to inactivate helminth eggs, notably Ascaris lumbricoides,
      are recommended in the literature, but in practice these have not always proven
      effective, not only for Ascaris but also other genera of helminth eggs. The
      objective of this research was to study the inactivation of a high total content
      of non larval Ascaris and other genera of helminth eggs of medical importance to
      developing countries under controlled conditions of (a) temperature (30  degrees
      C to 80  degrees C) and humidity (80, 90 and 95%) and (b) lime doses (15 and 20%
      of CaO w/w dry basis) and humidity (90 and 80%), using different contact times in
      both cases. The inactivation data obtained for different genera of non larval
      helminth eggs is presented. Results showed that there is a combination of
      conditions (temperature, pH and humidity) that is optimal for inactivation. To
      completely inactivate any genera of non larval helminth eggs: (a) a temperature
      above 70  degrees C and 80% humidity for a duration of 120 min; and, (b) a 20%
      CaO dose (pH 12.5) and a humidity level of 80% for a duration of 8 months are
      needed. With regard to the resistance of different genera of helminth eggs,
      Ascaris, Toxocara and Taenia, in that order, were the most resistant, while the
      most sensitive were Trichuris and Hymenolepis. For most of the conditions tested
      Ascaris showed the highest resistance, probably due to the chemical arrangement
      of its membrane.

PMID- 21099050
TI  - Evaluation of manganese peroxidase (MnP) for its ability to resist the
      ozonization and thereafter decolorize methyl orange.
AB  - The goal of this study was to determine whether ozone can be used to suppress
      bacterial growth in operating a white rot fungi reactor system. The effects of
      ozone dose on the activity of manganese peroxidase (MnP) and on the death rate of
      Escherichia coli were investigated. The results showed that at ozone dose of 0.98
      mg/L the MnP activity was not affected after 40 min continuous treatment while
      the Escherichia coli inactivation rate can reach 99.9% after 30 min; In addition,
      the MnP that exposed to ozone dose of 1.56 mg/L for 40 min maintained their
      activity for decolorization of Methyl Orange. After 16 h, the decolorization rate
      of Methyl Orange was about 41%. These results showed that MnP have the ability to
      resist to some extent the attack of ozonization, which suggest that ozone might
      have its potential in suppressing the bacteria contamination in operating the
      white rot fungi reactor.

PMID- 21099052
TI  - Production and characterization of lignocellulosic biomass-derived activated
      carbon.
AB  - The goal of this work is to establish the technical feasibility of producing
      activated carbon from pulp mill sludges. KOH chemical activation of four
      lignocellulosic biomass materials, two sludges from pulp mills, one sludge for a
      linerboard mill, and cow manure, were investigated experimentally, with a focus
      on the effects of KOH/biomass ratio (1/1, 1.5/1 and 2/1), activation temperature
      (400-600  degrees C) and activation time (1 to 2 h) on the development of
      porosity. The activation products were characterized for their physical and
      chemical properties using a surface area analyzer, scanning electron microscopy
      and Fourier transform infrared spectroscopy. Experiments were carried out to
      establish the effectiveness of the lignocellulosic biomass-derived activated
      carbon in removing methylene blue (MB), a surrogate of large organic molecules.
      The results show that the activated carbon are highly porous with specific
      surface area greater than 500 m2/g. The yield of activated carbon was greater
      than the percent of fixed carbon in the dry sludge, suggesting that the
      activation process was able to capture a substantial amount of carbon from the
      organic matter in the sludge. While 400  degrees C was too low, 600  degrees C
      was high enough to sustain a substantial rate of activation for linerboard
      sludge. The KOH/biomass ratio, activation temperature and time all play important
      roles in pore development and yield control, allowing optimization of the
      activation process. MB adsorption followed a Langmuir isotherm for all four
      activated carbon, although the adsorption capacity of NK-primary sludge-derived
      activated carbon was considerably lower than the rest, consistent with its lower
      specific surface area.

PMID- 21099051
TI  - Oxidation of acetyl-pyrimidine wastewater by Fenton process.
AB  - In this study, contaminant degradation, priority performance, intermediates, and
      kinetics in catalytic oxidation of Acetyl-Pyrimidine wastewater by Fenton reagent
      were investigated. In batch experiments, the main parameters that govern the
      complex reactive system, i.e. temperature, pH, Fe2+, and H2O2 initial
      concentrations have been studied. The results showed total COD and Acetyl
      Pyrimidine removal was above 50% and 90% respectively under the following
      oxidation conditions: T at 25  degrees C, pH at 3.5, H2O2 at 300 mmol/l, Fe2+ at
      40 mmol/l, with the reaction time 2 h. Control experiment and UV-Infrared
      spectrums analysis indicated that Acetyl-Pyrimidine was removed prior to the
      small molecule organic. The reaction fit to a first-order rate equation and the
      activation energy of Pyrimidine was 2.365 kJ/mol.

PMID- 21099054
TI  - Synthesis and characterization of composite polysulfone membranes for
      desalination in nanofiltration technique.
AB  - Composite nanofiltration (NF) membrane was developed polyacrylic acid (PAA) in
      situ UV graft polymerization process using ultrafiltration (UF) polysulfone (PSF)
      membrane as porous support. FT-IR spectra indicated that grafting was performed
      and it show peaks at 1,732 cm-1 and 3,396 cm-1 region for CO and OH starching
      bond of acrylic acid (AA) monomer, respectively. AFM microscopy showed the
      roughness of surface was reduced by increase of UV irradiation times. Effect of
      irradiation time on the grafting of acrylic acid (AA) in the same concentration
      was discussed. The salts rejection increase was accompanied with grafting of
      polysulfone (PSF) ultrafiltration (UF) membrane. The rejection of Na2SO4, MgSO4,
      NaCl and CaCl2 salts by PSF-grafted-PAA nanofiltration (NF) membrane was in 98,
      60, 52 and 30% respectively, under 0.3 MPa.

PMID- 21099053
TI  - Application of acidic thermal treatment for one- and two-stage anaerobic
      digestion of sewage sludge.
AB  - The effectiveness of acidic thermal treatment (ATT) was examined in a 106-day
      continuous experiment, when applied to one- or two-stage anaerobic digestion of
      sewage sludge (4.3% TS). The ATT was performed at 170  degrees C and pH 5 for 1
      hour (sulfuric acid for lowering pH). The one-stage process was mesophilic at 20
      days hydraulic retention time (HRT), and incorporated the ATT as pre-treatment.
      The two-stage process consisted of a thermophilic digester at 5 days HRT and a
      mesophilic digester at 15 days HRT, and incorporated the ATT as interstage
      treatment. On average, VSS reduction was 48.7% for the one-stage control, 65.8%
      for the one-stage ATT, 52.7% for the two-stage control and 67.6% for the two
      stage ATT. Therefore, VSS reduction was increased by 15-17%, when the ATT was
      combined in both one- and two-stage processes. In addition, the dewaterability of
      digested sludge was remarkably improved, and phosphate release was enhanced. On
      the other hand, total methane production did not differ significantly, and color
      generation was noted in the digested sludge solutions with the ATT. In
      conclusion, the anaerobic digestion with ATT can be an attractive alternative for
      sludge reduction, handling, and phosphorus recovery.

PMID- 21099055
TI  - Geosmin and 2-methylisoborneol adsorption on super-powdered activated carbon in
      the presence of natural organic matter.
AB  - Geosmin and 2-methylisoborneol (2-MIB) are naturally occurring compounds
      responsible for musty-earthy-odors in surface water supplies. They are a severe
      problem confronting utilities worldwide. Adsorption by powdered activated carbon
      (PAC) is a widely used process to control this problem, but it has low
      efficiency, which engenders large budget spending for utilities services. Super
      powdered activated carbon (S-PAC) is activated carbon with much finer particles
      than those of PAC. Experiments on geosmin and 2-MIB adsorptions on S-PAC and PAC
      were conducted. Geosmin and 2-MIB adsorption capacities on S-PAC were not smaller
      than those on PAC although natural organic matter, which adversely impacted the
      adsorption capacity of geosmin and 2-MIB, was more adsorbed on S-PAC than on PAC,
      meaning that the adsorption competition is less severe for S-PAC than for PAC.

PMID- 21099056
TI  - Coupling of anodic oxidation and adsorption by granular activated carbon for
      chemical oxygen demand removal from 4,4'-diaminostilbene-2,2'-disulfonic acid
      wastewater.
AB  - Experiments were performed to reduce chemical oxygen demand (COD) from 4,4'
      diaminostilbene-2,2'-disulfonic (DSD) acid manufacturing wastewater using
      electrochemical oxidation coupled with adsorption by granular activated carbon.
      The COD removal is affected by the residence time and applied voltage. When the
      residence time is increased, lower value of COD effluent could be obtained,
      however, the average current efficiency (ACE) decreased rapidly, and so does the
      applied voltage. In addition, aeration could effectively enhance COD removal
      efficiency and protect anodes from corrosion. Furthermore, the acidic condition
      is beneficial to the rapid decrease of COD and the values of pH effluent are
      independent of the initial solution pH. The optimization conditions obtained from
      these experiments are applied voltage of 4.8 V, residence time of 180 min and air
      liquid ratio of 4.2 with the COD effluent of about 690 mg L-1. In these cases,
      the ACE and energy consumption are 388% and 4.144 kW h kg-1 COD, respectively.
      These perfect results from the experiments illustrate that the combined process
      is a considerable alternative for the treatment of industrial wastewater
      containing high concentration of organic pollutants and salinity.

PMID- 21099057
TI  - Comparative study of different formulations and solution methods for two phase
      flow in saturated porous media.
AB  - Six models (Simulators) are formulated and developed with all possible
      combinations of pressure and saturation of the phases as primary variables. A
      comparative study between six simulators with two numerical methods, conventional
      simultaneous and modified sequential methods are carried out. The results of the
      numerical models are compared with the laboratory experimental results to study
      the accuracy of the model especially in heterogeneous porous media. From the
      study it is observed that the simulator using pressure and saturation of the
      wetting fluid (P(W), S(W) formulation) is the best among the models tested. Many
      simulators with nonwetting phase as one of the primary variables did not converge
      when used along with simultaneous method. Based on simulator 1 (P(W), S(W)
      formulation), a comparison of different solution methods such as simultaneous
      method, modified sequential and adaptive solution modified sequential method are
      carried out on 4 test problems including heterogeneous and randomly heterogeneous
      problems. It is found that the modified sequential and adaptive solution modified
      sequential methods could save the memory by half and as also the CPU time
      required by these methods is very less when compared with that using simultaneous
      method. It is also found that the simulator with P(NW) and P(W) as the primary
      variable which had problem of convergence using the simultaneous method,
      converged using both the modified sequential method and also using adaptive
      solution modified sequential method. The present study indicates that pressure
      and saturation formulation along with adaptive solution modified sequential
      method is the best among the different simulators and methods tested.

PMID- 21099058
TI  - Exposure assessment of metal intakes from drinking water relative to those from
      total diet in Japan.
AB  - Daily intakes of 17 metals (boron, aluminium, chromium, manganese, nickel,
      copper, zinc, arsenic, selenium, molybdenum, cadmium, antimony, lead, uranium,
      magnesium, calcium, and iron) via drinking water and total diet were investigated
      in six cities in Japan. The daily metal intakes were estimated and compared with
      tolerable daily intake (TDI) values proposed by the WHO or Joint FAO/WHO Expert
      Committee on Food Additives for toxic metals and with recommended dietary
      allowances (RDAs) or adequate intake (AI) values proposed for essential metals by
      the Japanese Ministry of Health, Labour and Welfare. Among the 13 toxic metals,
      mean dietary intakes of 10 (except arsenic, selenium, and molybdenum) were less
      than 50% of TDI, suggesting that for these 10 metals the allocation of intake to
      drinking water in establishing guidelines or standards could possibly be
      increased from the normal allocation of 10-20% of TDI. For the 13 toxic metals,
      the contribution of drinking water to TDI was 2% or less in all six cities. Mean
      dietary intakes of the essential elements magnesium, calcium, and iron were less
      than the RDA or AI values. Drinking water did not contribute much to essential
      metal intake, accounting for less than 10% of RDA or AI.

PMID- 21099059
TI  - Subsurface iron and arsenic removal: low-cost technology for community-based
      water supply in Bangladesh.
AB  - The principle of subsurface or in situ iron and arsenic removal is that aerated
      water is periodically injected into an anoxic aquifer through a tube well,
      displacing groundwater containing Fe(II). An oxidation zone is created around the
      tube well where Fe(II) is oxidised. The freshly formed iron hydroxide surfaces
      provide new sorption sites for soluble Fe(II) and arsenic. The system's
      efficiency is determined based on the ratio between abstracted volume with
      reduced iron/arsenic concentrations (V) and the injected volume (V(i)). In the
      field study presented in this paper, the small-scale application of this
      technology was investigated in rural Bangladesh. It was found that at small
      injection volumes (<1 m3) iron removal was successful and became more effective
      with every successive cycle. For arsenic, however, the system did not prove to be
      very effective yet. Arsenic retardation was only limited and breakthrough of 10
      ug/L (WHO guideline) was observed before V/V(i)=1, which corresponds to arrival
      of groundwater at the well. Possible explanations for insufficient arsenic
      adsorption are the short contact times within the oxidation zone, and the
      presence of competing anions, like phosphate.

PMID- 21099060
TI  - Upgrading of an activated sludge wastewater treatment plant by adding a moving
      bed biofilm reactor as pre-treatment and ozonation followed by biofiltration for
      enhanced COD reduction: design and operation experience.
AB  - A paper mill producing 500,000 ton of graphic paper annually has an on-site
      wastewater treatment plant that treats 7,240,000 m3 of wastewater per year,
      mechanically first, then biologically and at last by ozonation. Increased paper
      production capacity led to higher COD load in the mill effluent while production
      of higher proportions of brighter products gave worse biodegradability. Therefore
      the biological capacity of the WWTP needed to be increased and extra measures
      were necessary to enhance the efficiency of COD reduction. The full scale
      implementation of one MBBR with a volume of 1,230 m3 was accomplished in 2000
      followed by another MBBR of 2,475 m3 in 2002. An ozonation step with a capacity
      of 75 kg O3/h was added in 2004 to meet higher COD reduction demands during the
      production of brighter products and thus keeping the given outflow limits. Adding
      a moving bed biofilm reactor prior to the existing activated sludge step gives:
      (i) cost advantages when increasing biological capacity as higher COD volume
      loads of MBBRs allow smaller reactors than usual for activated sludge plants;
      (ii) a relief of strain from the activated sludge step by biological degradation
      in the MBBR; (iii) equalizing of peaks in the COD load and toxic effects before
      affecting the activated sludge step; (iv) a stable volume sludge index below 100
      ml/g in combination with an optimization of the activated sludge step allows good
      sludge separation--an important condition for further treatment with ozone.
      Ozonation and subsequent bio-filtration pre-treated waste water provide: (i)
      reduction of hard COD unobtainable by conventional treatment; (ii) controllable
      COD reduction in a very wide range and therefore elimination of COD-peaks; (iii)
      reduction of treatment costs by combination of ozonation and subsequent bio
      filtration; (iv) decrease of the color in the ozonated wastewater. The MBBR step
      proved very simple to operate as part of the biological treatment. Excellent
      control of the COD-removal rate in the ozone step allowed for economical usage
      and therefore acceptable operation costs in relation to the paper production.

PMID- 21099061
TI  - Screening of pharmaceuticals and endocrine disrupting compounds in water supplies
      of Cyprus.
AB  - Cyprus is currently the leading country in antibiotic consumption among all
      European Union member countries and is likely to have a high consumption of
      pharmaceuticals overall. This reconnaissance type of project sought to
      investigate the occurrence of 16 pharmaceuticals, six known or suspected
      endocrine disrupting compounds (EDCs), two flame retardants, one insect
      repellant, and one fragrance for the first time in water supplies of Cyprus.
      Groundwater samples from sites that were located beneath farms scattered around
      Cyprus, wastewater influent and tertiary-treated effluent, raw and finished
      surface water, and household potable water samples were analyzed using liquid
      chromatography and tandem mass spectrometry. Most of the tested compounds were <
      minimum reporting limit, except for ibuprofen (mean of 1.4 ng L-1) and bisphenol
      A (mean of 50 ng L-1), which were detected in more than one out of the five
      groundwater sampling sites. Certain compounds were found in large concentrations
      in the wastewater influent (caffeine 82,000 ng L-1, sulfamethoxazole 240 ng L-1,
      ibuprofen 4,300 ng L-1, and triclosan 480 ng L-1. However, several
      pharmaceuticals and EDCs were detected in the tertiary-treated effluent (recycled
      water). For the raw and finished surface water, and potable water samples,
      ibuprofen was detected, whereas, bisphenol-A was measured in only potable water.
      Overall, with a few notable exceptions, source, finished and potable water had
      rare detection or low concentration of target compounds, but further research is
      needed to elucidate the temporal and spatial distribution of the detected
      emerging contaminants along with the characterization of the related public
      health risk.

PMID- 21099063
TI  - Transdisciplinary care: opportunities and challenges for behavioral health
      providers.

PMID- 21099064
TI  - Preventing opiate overdose deaths: examining objections to take-home naloxone.
AB  - Opiate overdose persists as a major public health problem, contributing to
      significant morbidity and mortality among opiate users globally. Opiate overdose
      can be reversed by the timely administration of naloxone. Programs that
      distribute naloxone to opiate users and their acquaintances have been
      successfully implemented in a number of cities around the world and have shown
      that non-medical personnel are able to administer naloxone to reverse opiate
      overdoses and save lives. Objections to distributing naloxone to non-medical
      personnel persist despite a lack of scientific evidence. Here we respond to some
      common objections to naloxone distribution and their implications.

PMID- 21099066
TI  - Predictors of employment status among African Americans with sickle cell disease.
AB  - Adults living with sickle cell disease (SCD) have extremely high rates of
      unemployment; however, very little is known about factors that contribute to
      their vocational outcomes. This study examined demographic, illness perception,
      and psychological variables as predictors of employment status among 115 adult
      respondents who completed a cross-sectional survey as part of the Cooperative
      Study of Sickle Cell Disease. Logistic regression analysis indicated that gender,
      assertiveness, and perceived impact of SCD were unique predictors of employment
      status. Women were 2.88 times more likely to be employed than men, and the odds
      of being employed increased by a factor of 2.47 for each one unit decrease in
      assertiveness. More favorable perceptions of SCD were also associated with a two
      fold increase in employment. The results suggest that demographic and
      psychosocial factors may play a more important role in predicting employment
      outcomes in adults with SCD than previously recognized.

PMID- 21099065
TI  - Problematic hospital experiences among adult patients with sickle cell disease.
AB  - BACKGROUND: Adults with sickle cell disease (SCD) have often reported
      difficulties obtaining care during vaso-occlusive crisis (VOC) in qualitative
      studies. METHODS: We measured the experiences of 45 SCD patients who received in
      hospital care for VOC using the Picker Patient Experience Questionnaire (PPE-15),
      and used the one sample binomial test to compare with national norms. RESULTS:
      Most SCD patients reported that they were insufficiently involved in decisions
      (86%), staff gave conflicting information (64%), it wasn't easy to find someone
      to discuss concerns (61%), doctors' answers to questions were not clear (58%),
      nurses' answers to questions were not clear (56%), doctors did not always discuss
      fears and anxieties (53%), and nurses did not always discuss fears and anxieties
      (52%). A greater percentage of SCD patients than the U.S. sample in 9 of 12 areas
      reported problems. CONCLUSIONS: Further research is needed to determine the
      consequences of and potential interventions to improve these poor experiences.

PMID- 21099067
TI  - Surveillance after colorectal cancer diagnosis in a safety net hospital.
AB  - Our objective was to assess colorectal cancer (CRC) surveillance among a diverse
      patient population receiving care at a safety net hospital. We used
      administrative and clinical data to identify patients with a non-metastatic CRC
      diagnosis. We identified whether endoscopic surveillance occurred within one or
      three years of resection. Of the 253 CRC patients, 56% had colonoscopic
      surveillance within three years, but only 27% within one year of resection.
      Timely surveillance was more common for male, married, or more educated patients,
      those with more visits, and those with fewer comorbidities. After adjusting for
      confounders, there were no racial/ethnic differences in timely one-year
      surveillance, yet Black patients were more likely than Whites to receive timely
      three-year surveillance. In this safety net hospital, post-resection CRC
      surveillance was provided independent of patients' ability to pay. While care is
      equitable and favorable for Black patients, opportunities exist to increase
      timely surveillance of patients.

PMID- 21099068
TI  - A national study of problematic care experiences among Latinos with diabetes.
AB  - Despite the large disease burden of diabetes, little is known about the care
      experiences of Latinos with diabetes across diverse primary care settings. This
      study compares problematic care experiences among Latinos with diabetes across
      usual care sites (community health centers [CHCs], private physician practices,
      or without a usual source of care), using a national sample of Latino diabetic
      patients (N=583). Nearly half of the respondents reported at least one
      problematic care experience during their last clinician visit. Compared with
      respondents treated primarily by private physicians, respondents receiving care
      in CHCs or without a usual source of care reported more problematic care
      experiences. However, patient health insurance coverage and acculturation
      accounted for the highest proportion of explainable differences in problematic
      care experiences between CHCs and private physician offices. Initiatives should
      clarify the extent to which the care experiences of Latino diabetics,
      particularly uninsured and less acculturated patients who tend to be cared for by
      CHCs, can be improved through clinician communication and patient self-management
      interventions.

PMID- 21099069
TI  - Characteristics of ambulatory care patients and services: a comparison of
      community health centers and physicians' offices.
AB  - The overall aim was to determine whether health care delivery for vulnerable
      populations served by community health centers (CHCs) was comparable to care for
      mainstream Americans primarily seen in physicians' offices (POs). Data came from
      the 2006 National Ambulatory Medical Care Survey. Patient visits occurring in
      CHCs were largely from younger, uninsured or Medicaid-insured, minority
      populations, while POs catered mainly to older, Medicare- or privately-insured,
      White patients. Communities served by CHCs were more often in low-income, low
      education, urban regions. A greater proportion of visits to CHCs were from
      diabetic, obese, and depressed patients; CHCs also offered more evening/weekend
      visits and provided more health education during visits, but spent less time per
      visit than POs and had more difficulty referring patients to specialists. Results
      affirmed the significant role of CHCs as safety-net providers for vulnerable
      populations, and indicated that CHCs provide adequate care compared with POs
      although there remains room for improvement.

PMID- 21099070
TI  - Cardiovascular risk in African American women attending historically Black
      colleges and universities: the role of dietary patterns and food preferences.
AB  - There is a lack of data on the dietary patterns and food preferences of African
      American women attending historically Black colleges and universities (HBCUs).
      African American women have higher death rates from cardiovascular disease than
      White women, and the initiating events of cardiovascular disease often begin in
      young adulthood. The purpose of this study was to identify the dietary patterns
      and food preferences of African American college women, which may act as risk
      factors for cardiovascular disease. A convenience sample of 100 African American
      women, ages 18 to 40 years, was administered two surveys assessing food
      preferences and dietary patterns. The majority of the participants (65%)
      preferred high-fat foods, and most of the participants (87%) consumed more than
      30% of their daily caloric intake from fat. There is a definite need for dietary
      education regarding the impact of dietary fat on cardiovascular health among
      college students.

PMID- 21099071
TI  - Incarceration as a risk factor for hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV) co-infection in Mississippi.
AB  - BACKGROUND: Injection drug use (IDU) is the most commonly recognized risk factor
      for co-infection with human immunodeficiency virus (HIV) and hepatitis C virus
      (HCV). We examined risks for HIV/HCV co-infection in a population with a low rate
      of IDU. METHODS: A sample of 32 HIV/HCV co-infected patients and 79 HIV-infected
      patients were enrolled from two clinics in Mississippi. Patients completed an
      audio computer-assisted self-interview (ACASI) assessing risks for infection with
      both viruses. RESULTS: In a multivariable logistic regression model, greater age
      (p=.01), alcohol use (p=.02), history of incarceration (p=.04), and blood
      transfusion prior to 1992 (p=.03) were independently associated with HIV/HCV co
      infection. CONCLUSIONS: Incarceration was significantly associated with HIV-HCV
      co-infection in our sample. Further examination is warranted to develop policies
      for HCV prevention and treatment within the prison system.

PMID- 21099072
TI  - Physical activity correlates for Native Hawaiians and Pacific Islanders in the
      mainland United States.
AB  - Native Hawaiian and Pacific Islander (NHPI) people are an understudied population
      that demonstrates high obesity rates and low physical activity levels. This
      study's aim was to examine possible correlates of physical activity in NHPI
      adults. Height and weight were recorded in N=100 NHPIs (46.9+/-5.4 years; 56%
      males) following completion of an anonymous questionnaire addressing health
      behaviors (physical activity, smoking, diet), psychosocial characteristics
      (social support, barriers, stage of change), neighborhood environment attributes,
      and knowledge of physical activity recommendations. This study sample
      demonstrated low physical activity (20% met recommendations) and fruit and
      vegetable (F&V) consumption (1% met recommendations), and a high prevalence of
      overweight or obesity (94%). After adjusting for gender and education, F&V intake
      was the only significant correlate of physical activity (p<.001). Common
      correlates of physical activity did not generalize to NHPIs. Further
      investigations of culturally-specific correlates are needed so that physical
      activity interventions can be culturally tailored for NHPIs.

PMID- 21099073
TI  - Health, occupational and environmental risks of emancipated migrant farmworker
      youth.
AB  - This study examines the perceptions of health, health seeking behavior, access to
      information and resources, work related hazards, substance abuse, and social
      support of emancipated migrant youth (EMY) who come to the United States without
      their families to work. METHODS: Semi-structured interviews were performed with
      EMY living without their families in Santa Clara County, California. Interviews
      were digitally recorded in Spanish, transcribed, translated into English, and
      analyzed by a five-person analysis team. RESULTS: Eleven interviews were
      conducted with 29 participants. Work was identified as the overarching priority
      of the EMY Their greatest concern was becoming sick and unable to work. They
      described their work environment as demanding and stressful, but felt obliged to
      work regardless of conditions. Alcohol and drug abuse were reported as prevalent
      problems. CONCLUSION: Emancipated migrant youth are a vulnerable population who
      have significant occupational stress, hazardous environmental exposures, social
      isolation, and drug/alcohol abuse.

PMID- 21099074
TI  - Food insecurity is associated with hypoglycemia and poor diabetes self-management
      in a low-income sample with diabetes.
AB  - More than 14% of the American population is food insecure, or at risk of going
      hungry because of an inability to afford food. Food-insecure (FI) adults often
      reduce food intake or substitute inexpensive, energy-dense carbohydrates for
      healthier foods. We hypothesized these behaviors would predispose FI adults with
      diabetes to hypoglycemia and impaired diabetes self-management. We therefore
      assessed whether food insecurity was associated with multiple indicators of
      diabetes self-management (self-efficacy, medication- and glucose-monitoring
      adherence, hypoglycemia, or glycemic control) among 40 low-income adults with
      diabetes. Mean self-efficacy score was lower among FI than food-secure (FS)
      participants (34.4 vs. 41.2, p=.02). Food-insecure participants reported poorer
      adherence to blood glucose monitoring (RR=3.5, p=.008) and more hypoglycemia
      related emergency department visits (RR=2.2, p=.007). Mean hemoglobin A1c was
      9.2% among FI and 7.7% among FS participants (p=.08). Food insecurity is a
      barrier to diabetes self-management and a risk factor for clinically significant
      hypoglycemia.

PMID- 21099075
TI  - Mental health correlates of past homelessness in the National Comorbidity Study
      Replication.
AB  - This study uses data from a nationally representative epidemiologic survey, the
      National Comorbidity Survey Replication, to investigate the association of mental
      health and substance use disorders, along with other factors, with past
      homelessness. Approximately 5% of the 5,251 adults reported having been
      homelessness. Multivariate analysis showed the strongest independent risk factors
      for past homelessness were past receipt of welfare payments (odds ratio
      [OR]=5.7), incarceration for 27 or more days (OR=3.9), exposure to personal
      violence (OR=2.7), lifetime substance use disorder (OR=2.4), and Black race
      (OR=2.1). Several non-substance use psychiatric disorders were also
      significantly, if less strongly (OR 1.4 to 1.6), associated with past
      homelessness. Past homelessness is associated with a broad array of
      sociodemographic, economic, and mental health problems. While the association of
      both substance use and psychiatric disorders with past homelessness was quite
      strong, non-substance use psychiatric disorders was not as strong an independent
      risk factor as substance abuse disorders.

PMID- 21099076
TI  - Correlates of adult assault among homeless women.
AB  - The purpose of this study was to assess predictors of sexual and physical assault
      among homeless women. A multivariate, correlation design was utilized to identify
      independent correlates of adult physical and sexual assault. The sample consisted
      of 202 homeless women residing in shelters or living on the street in the Skid
      Row area of Los Angeles. Respondents reporting a history of child sexual abuse
      were almost four times more likely to report being sexually assaulted as adults
      and were almost two and one third times more likely to report being physically
      assaulted as adults. A range of factors increase homeless women's risk of adult
      physical and sexual victimization, including child sexual abuse, substance use,
      lifetime sex trade activity, and previous incarceration. It is important for
      homeless service providers to develop an individual risk profile for homeless
      women and to intervene in order to decrease their risk of re-victimization.

PMID- 21099077
TI  - Correlates of age at onset of sexual intercourse in African American adolescents
      living in urban public housing.
AB  - Research has found the early onset of sexual activity (having sexual intercourse
      before age 13) among adolescents to be related to teen pregnancy and a range of
      health-risk behaviors and higher rates of sexually transmitted infections (STIs)
      and HIV/AIDS. These findings are most prevalent in urban African American
      adolescents. Using a sample of 299 sexually active African American adolescents
      living in public housing developments in a large Northeast and a large Mid
      Atlantic city, this study assesses the influence of family, peers, and the
      individual on the age of onset of sexual intercourse. All participants completed
      surveys in their housing developments. Results indicate an average age of onset
      of 14. Males reported a significantly younger age of onset and more sexual
      partners than females. Exposure to delinquent peers and self-efficacy were
      significant predictors of age of onset. Implications for practice are discussed.

PMID- 21099078
TI  - Running on empty: health care energy use in a developing country.
AB  - Health care systems require reliable energy for high-quality services. Rising
      fossil fuel prices globally limit the capacity of developing countries to provide
      continuous and essential health care services. Global health care projects should
      focus on energy innovation for health care use.

PMID- 21099079
TI  - Georgia's Utilization Minigrant Program: promoting Medicaid/CHIP outreach.
AB  - Funded community-based organizations improved utilization of children's health
      services by developing innovative staffing patterns, creating new data systems
      for scheduling appointments and maintaining records, and forging new
      collaborative relationships to leverage financial support. These strategies were
      rooted in collaboration with community-based organizations, health care
      providers, and the state Medicaid agency.

PMID- 21099080
TI  - Health professional students in community service: insights from trainees and
      their mentors.
AB  - OBJECTIVES: To gain insights from the experiences of student health professionals
      working with agencies caring for the underserved. METHODS: Five hundred and sixty
      six (566) U.S. Albert Schweitzer Fellows from 90 professional schools in six
      sites participated in year-long mentored, entrepreneurial service and leadership
      development projects in community agencies. Focusing on their experiences,
      Fellows completed pre- and post-service surveys, and agency mentors completed a
      post-service survey about their experiences. RESULTS: Fellows' confidence in 11
      of 16 service-related skills increased, and their concerns about lack of
      knowledge, skills, experience, recognition, and mentoring as barriers to service
      decreased. Their concerns about time constraints increased. Agency mentors
      reported that 85% of Fellows' projects made significant contributions to their
      agencies or clients. CONCLUSIONS: An entrepreneurial, mentored service experience
      can have a positive impact on health professional students and may provide
      benefits to the communities served.

PMID- 21099081
TI  - Conducting telephone interviews with community-dwelling older adults in a state
      Medicaid program: differences by ethnicity and language preference.
AB  - We document the methodological challenges of conducting a health survey of an
      ethnically diverse elderly community-dwelling Medicaid population by telephone.
      Individuals (N=5,382) 65 years and older were randomly selected from a state
      Medicaid Management Information System and 618 eligible participants were
      interviewed. Participants were classified as non-Hispanic White, English-speaking
      (NHW-E; 69.2%), non-Hispanic Black, English-speaking (NHB-E; 6.2%), Hispanic,
      Spanish-speaking (H-S; 9.2%), and Hispanic, English-speaking (H-E; 4.2%). Almost
      half (44.2%) of the individuals sampled were unreachable, most often because of
      no valid telephone number. More interviewer time was required to reach and
      interview Hispanic participants. On average, interviews with H-S and H-E were 11
      and 8 minutes longer, respectively, than with NHW-E. Spanish-speaking Hispanic
      respondents reported very high rates of receipt of preventive services relative
      to the other groups. These high rates by Spanish-speakers may be due to actual
      greater utilization or biases in self-reported data due to response style
      differences.

PMID- 21099082
TI  - Priorities of low-income urban residents for interventions to address the socio
      economic determinants of health.
AB  - OBJECTIVES: To determine the priorities of low-income urban residents for
      interventions that address the socio-economic determinants of health. METHODS: We
      selected and estimated the cost of 16 interventions related to education,
      housing, nutrition, employment, health care, healthy behavior, neighborhood
      improvement, and transportation. Low-income residents of Washington, D.C. (N=431)
      participated in decision exercises to prioritize these interventions. RESULTS:
      Given a budget valued at approximately twice an estimated cost of medical and
      dental care ($885), the interventions ultimately prioritized by the greatest
      percentage of individuals were: health insurance (95%), housing vouchers (82%)
      dental care (82%), job training (72%), adult education (63%), counseling (68%),
      healthy behavior incentives (68%), and job placement (67%). The percentages of
      respondents who received support for housing, adult education, and job training
      and placement were far less than the percentage who prioritized these
      interventions. CONCLUSIONS: Poor and low-income residents' priorities may
      usefully inform allocation of social services that affect health.

PMID- 21099083
TI  - Service provider perceptions of long-term care access in American Indian and
      Alaska Native communities.
AB  - BACKGROUND: The need for long-term care services for American Indians and Alaska
      Natives (AI/ANs) is great since this population is experiencing some of the
      highest rates in the United States of chronic disease and disability. METHODS:
      Between 2005 and 2007, a survey on access and barriers to long-term care was
      mailed to key informants at 305 tribes and tribal consortia. Targeted key
      informants included Health Directors, Social Service Directors, Older Americans
      Act Title VI Directors, and Community Health Representative or Community Health
      Aide Directors. Survey-adjusted data were analyzed descriptively. RESULTS: Four
      hundred and forty-two respondents returned surveys representing 220 tribes and
      consortia. Human services were overall more available than health services. There
      was a high level of interest for long-term care services among consumers and
      tribal leaders. Funding issues were the most prevalent reported factors adversely
      affecting long-term care development. CONCLUSIONS: Efforts are needed to improve
      AI/ANs access to these services.

PMID- 21099084
TI  - Methodological issues in the collection, analysis, and reporting of granular data
      in Asian American populations: historical challenges and potential solutions.
AB  - There are close to 15 million Asian Americans living in the United States, and
      they represent the fastest growing populations in the country. By the year 2050,
      there will be an estimated 33.4 million Asian Americans living in the country.
      However, their health needs remain poorly understood and there is a critical lack
      of data disaggregated by Asian American ethnic subgroups, primary language, and
      geography. This paper examines methodological issues, challenges, and potential
      solutions to addressing the collection, analysis, and reporting of disaggregated
      (or, granular) data on Asian Americans. The article explores emerging efforts to
      increase granular data through the use of innovative study design and analysis
      techniques. Concerted efforts to implement these techniques will be critical to
      the future development of sound research, health programs, and policy efforts
      targeting this and other minority populations.

PMID- 21099085
TI  - Benefit policy and disenrollment of adult Medicaid beneficiaries from the Oregon
      health plan.
AB  - Oregon's Medicaid program experienced a dramatic decrease in its non
      categorically eligible adult members after implementing a new benefit policy in
      February 2003 for these beneficiaries. The policy included four main elements:
      premium increases for some enrollees; a more stringent premium payment policy;
      elimination of some benefits, including mental health and substance abuse
      treatment; and, the imposition of co-payments. The study compared monthly
      disenrollment rates eight months before and after the policy change. The new
      premium payment policy was found to be the main driver of disenrollment, followed
      by benefit elimination. Premium increases and co-payments had limited impact.
      Disenrollment was particularly high among vulnerable beneficiary groups,
      including people with no reported income, those previously obtaining premium
      waivers, methadone users, and other enrollees with substance abuse conditions.
      Better understanding of the relationship between benefit design and retention in
      public health insurance programs could help avoid the unintended policy effects
      experienced in Oregon.

PMID- 21099086
TI  - Predictors of payment behavior among the medically uninsured: a prospective
      cohort study of patients seeking ambulatory services.
AB  - BACKGROUND: Little is known about the characteristics of uninsured patients who
      attempt to pay for their care. PURPOSE: This study sought to identify predictors
      of payment after receiving care at three urban hospitals. METHODOLOGY: One
      hundred and seventy uninsured ambulatory patients were interviewed about their
      health status, income, and credit and payment histories at the point of care.
      Eighteen months later, data on payment outcomes were extracted from the medical
      financial records for each subject. FINDINGS: Patients were more likely to make a
      payment if they reported higher income, health insurance for other services, or
      worrying about their credit. They were less likely to pay anything if they owed a
      large sum, were seeking care at the public site, or had received care in an
      emergency room. CONCLUSIONS: Specific characteristics of uninsured patients, the
      site of care, and the size of the bill are all associated with payment outcome.

PMID- 21099087
TI  - Whole-genome expression analysis of Mycobacterium leprae and its clinical
      application.
AB  - The whole-genome sequence analysis of Mycobacterium leprae, which was completed
      in 2001, revealed the characteristics of this microbe's genomic structure. Half
      of the M. leprae genome consists of a limited number of protein-coding genes and
      the rest comprises non-coding regions and pseudogenes. We performed membrane
      array and tiling array analyses to analyze the gene-expression profile of the M.
      leprae genome and found that pseudogenes and non-coding regions were expressed
      similarly to coding regions at the RNA level. The RNA expressions were confirmed
      by real-time PCR analysis. Expression of these RNAs in clinical samples showed
      varying patterns among patients, thus indicating that the analysis of RNA
      expression patterns, including non-coding regions and pseudogenes, may be useful
      for understanding the pathological state, prognosis, and assessment of
      therapeutic progress in leprosy.

PMID- 21099089
TI  - Laboratory colonization of Aedes japonicus japonicus (Diptera: Culicidae)
      collected in Narita, Japan and the biological properties of the established
      colony.
AB  - A laboratory colony of the mosquito Aedes japonicus japonicus, which has recently
      invaded the United States and is recognized as a highly competent vector of West
      Nile virus, was established from larvae collected in Narita, Japan. The
      mosquitoes were maintained with induced insemination, blood-feeding on humans,
      and oviposition in water provided from the original collection site during the
      first few generations, then the colony was transferred to a large cage (40*40*100
      cm in height) and adapted to conditions in which specimens were allowed to mate
      freely. White mice were provided as the blood source, and deionized water was
      available for oviposition. Approximately 185 eggs, most of which were tolerant to
      desiccation for at least 1 month, with some surviving for up to 2.5 months, were
      obtained per female following a single blood-feeding. The rate of successful
      emergence was nearly 90%, although this rate decreased significantly at high
      larval densities. The colony has been maintained for 5 years, and developmental
      profiles of the species have been obtained during that time.

PMID- 21099088
TI  - Genotyping and phylogenetic analysis of the major genes in respiratory syncytial
      virus isolated from infants with bronchiolitis.
AB  - We performed the genotyping and phylogenetic analysis of respiratory syncytial
      virus (RSV) isolated from 17 infants with bronchiolitis in Kanagawa Prefecture,
      Japan in 2005 and 2006. The major genes in these samples (attachment [G]
      glycoprotein gene, fusion [F] protein gene, and nucleoprotein [N] gene) were
      sequenced and analyzed genetically. Phylogenetic analysis of these genes revealed
      that 7 and 10 strains could be classified into subgroups A and B, respectively.
      Phylogenetic analysis of the G gene revealed that the subgroup A and B strains
      were unique genotypes GA2 and BA, respectively. Moreover, the amino acid
      sequences for these genotypes suggested a relatively high frequency of amino acid
      substitutions in the G and F proteins in these strains, whereas the N protein was
      highly homologous. These results suggest that RSV genotypes GA2 and BA may be
      associated with bronchiolitis in the cases studied here.

PMID- 21099090
TI  - Molecular epidemiological study of rotavirus and norovirus infections among
      children with acute gastroenteritis in Nha Trang, Vietnam, December 2005-June
      2006.
AB  - A molecular epidemiological study of rotavirus (RV) and norovirus (NoV)
      infections was carried out in Nha Trang city in Vietnam between December 2005 and
      June 2006. RV and NoV were detected in 87 (47.5%) and 12 (6.6%) of the 183 fecal
      specimens from children hospitalized with acute gastroenteritis, respectively.
      The majority of patients with RV and NoV were children younger than 2 years of
      age. The most frequent RV genotypes detected were G3 (n=37, 42.5%) and G1 (n=28,
      32.2%) for G type, P[8] (n=61, 70.1%) for P type, and G3P[8] (n=33, 38.0%) and
      G1P[8] (n=18, 20.7%) for the G and P genotype combination. GII.12 was the most
      common genotype (6/12, 50%) for NoV, followed by GII.4 (4/12, 33.3%), and we also
      identified a rare type (GII.19). The results of this study highlight the
      increased incidence of G3P[8] and the presence of many OP354-like P[8] RVs, as
      well as the GII.4 2003 Asia variant of NoVs. Furthermore, the first case of
      GII.19 of NoV in Vietnam is reported.

PMID- 21099091
TI  - Possible mode of emergence for drug-resistant leprosy is revealed by an analysis
      of samples from Mexico.
AB  - Mexico is a country with sporadic leprosy cases, and the reemergence of drug
      resistance is a concern. In this study, molecular analysis of Mycobacterium
      leprae was employed to clarify the spread of drug-resistant leprosy. Thus, drug
      resistance-determining regions in the folP1, rpoB, and gyrA genes, which are
      associated with resistance to dapsone, rifampicin, and ofloxacin, respectively,
      were analyzed by direct sequencing of the PCR product. No mutations in the folP1
      gene were observed in any of the 72 slit skin samples obtained from 38 patients,
      although two samples carrying a mutation at codon 425 in the rpoB gene, which
      confers resistance to rifampicin, a key component of multidrug therapy, were
      identified. In addition, a mutation at codon 91 in the gyrA gene, which
      correlates with ofloxacin resistance, was found in one sample. These results
      demonstrate the existence of rifampicin- and ofloxacin-resistant leprosy.
      Interestingly, wild-type and mutant sequences in the gyrA gene were found to
      coexist in one clinical sample. In addition, all three drug resistance-related
      mutations were found in only one of the two earlobes of the patients concerned,
      suggesting a possible pathway for the spread of drug-resistant M. leprae.

PMID- 21099092
TI  - High prevalence of integron-mediated resistance in clinical isolates of
      Salmonella enterica.
AB  - Salmonella enterica has become progressively resistant to antimicrobial agents
      worldwide as a result of genes carried on different classes of integrons. The aim
      of the current study was to investigate the molecular diversity of these
      integrons and their association with antimicrobial resistance in clinical S.
      enterica isolates from Tehran, Iran. Antimicrobial susceptibility testing was
      performed according to the Clinical and Laboratory Standards Institute. The
      presence of integrons was investigated by PCR using specific primers. Integrons
      were detected in 65 (47.1%) strains, with classes 1 and 2 being observed in 54
      (39%) and 11 (8%) strains, respectively. Integron-positive isolates belonged to
      seven different S. enterica serovars, and all showed a multidrug-resistant (MDR)
      phenotype. Our findings show that integrons are widely disseminated among S.
      enterica strains from Tehran. Furthermore, the results that class 1 integrons
      were more prevalent than class 2 in Salmonella isolates, and that a statistical
      association with MDR patterns was observed, suggest that they are more likely to
      be important in conferring a resistant phenotype to Salmonella strains.

PMID- 21099093
TI  - Changing epidemiology of hand, foot, and mouth disease in Hong Kong, 2001-2009.
AB  - We report the surveillance findings of hand, foot, and mouth disease (HFMD)
      collected from a general practitioner-based sentinel surveillance system and
      outbreaks reported by institutions and a laboratory-based enterovirus
      surveillance system in Hong Kong from 2001 to 2009. A seasonal peak was detected
      in the warmer months (May-July), along with a smaller winter peak (October
      December) from 2006 onwards. The number of older children (>5 years) infected
      increased from 25.4% in 2001 to 33.0% in 2009 (P=0.01, Mantel-Haenszel chi-square
      test). Laboratory surveillance detected a cyclical high enterovirus 71 activity
      every 3 to 4 years. This activity was associated with a higher average
      hospitalization rate for HFMD patients in the outbreaks reported in the
      corresponding year, although the difference was only marginally significant
      (P=0.09, linear regression test). The changing epidemiology of HFMD warrants
      continuous surveillance in order to guide preventive public-health actions.

PMID- 21099094
TI  - Clinical and immunological assessment of periodontal disease in Japanese leprosy
      patients.
AB  - Periodontitis is a chronic inflammatory disease caused by the infection of
      periodontopathic bacteria in dental plaque. However, an individual's
      susceptibility to this disease appears to be associated with multiple genetic
      factors, as seen in the case of leprosy. In order to gain a better understanding
      of the pathophysiology of periodontal disease in subjects with leprosy, we
      investigated the clinical features of periodontitis and the immunological
      responses against periodontopathic bacteria in 382 subjects with a history of
      leprosy and 451 age-matched control subjects. The prevalence of periodontitis and
      the degree of periodontal pocket depth were found to be significantly higher in
      leprosy patients than in age-matched controls. Furthermore, a comparison of the
      clinical parameters of lepromatous leprosy (L-lep) and tuberculoid leprosy (T
      lep) patients showed that the probing pocket depth of L-lep patients with
      periodontal disease was significantly higher than that for T-lep patients. In
      contrast, serum IgG titers against Porphyromonas gingivalis in L-lep patients
      were significantly lower than in T-lep patients. These results imply that L-lep
      patients show more severe periodontal disease than T-lep patients or age-matched
      control subjects, and that low humoral immunity against P. gingivalis might be
      one of the genetic factors determining periodontal disease susceptibility in
      leprosy patients.

PMID- 21099095
TI  - Is the T-cell-based interferon-gamma releasing assay feasible for diagnosis of
      latent tuberculosis infection in an intermediate tuberculosis-burden country?
AB  - The diagnosis of active and latent tuberculosis infection (LTBI) remains a
      challenge, especially in light of the fact that the tuberculin skin test (TST),
      which has been used to diagnose LTBI for over a century, has many well-known
      drawbacks. This study aimed to compare the diagnostic performance of the T-cell
      based interferon-gamma releasing assay (IGRA) T-SPOT.TB with the TST for the
      diagnosis of LTBI in an intermediate tuberculosis (TB)-burden country with high
      BCG coverage. For this purpose, a total of 91 participants, including culture
      confirmed TB patients, healthy contacts known to have been exposed to
      Mycobacterium tuberculosis, and healthy volunteers, selected from a BCG
      vaccinated population were recruited. The sensitivities of the T-SPOT.TB and TST
      were 79.3 and 25.8%, and the specificities were 75.9 and 56.7%, respectively. The
      negative- and positive-predictive values for T-SPOT.TB and TST were 78.6 and
      76.7% and 42.5 and 38.1%, respectively. The diagnostic performance of the TST in
      LTBI diagnosis is therefore severely diminished in BCG-vaccinated populations,
      with the sensitivity and specificity of the T-SPOT.TB assay being markedly
      higher. IGRAs have been reported to have higher diagnostic sensitivity and
      specificity in low TB-incidence settings than those seen here. Further larger
      scale studies in high and intermediate TB-incidence settings are therefore
      warranted.

PMID- 21099096
TI  - Seroprevalence of syphilis in apparently healthy students from a tertiary
      institution in Benin City, Nigeria.
AB  - The seroprevalence of syphilis in students from a tertiary institution in Benin
      City, Nigeria was investigated. Venous blood samples (5 mL) were collected from
      214 apparently healthy students aged 19-38 years (118 males and 96 females)
      between February and October 2009 and the serostatus of syphilis determined
      qualitatively using the rapid plasma reagin test. Seropositive sera were
      confirmed using the Treponema pallidum hemagglutination test. The total
      seropositivity for syphilis was 15.4%, with a prevalence in males and females of
      18.6 and 11.4%, respectively. This difference was statistically significant
      (P<0.05). The highest prevalence was found for the 24-28-year-old age group,
      while the lowest prevalence was found for the 19-23-year-old age group, where no
      female tested positive. The results of this study show that the prevalence of
      syphilis infection among students in Benin City was high and is a public health
      concern. All persons, including voluntary blood donors, patients with sexually
      transmitted diseases, or those attending for routine medical checkups, should
      therefore be thoroughly screened for syphilis infection.

PMID- 21099097
TI  - Role of integrons in antimicrobial susceptibility patterns of Acinetobacter
      baumannii.
AB  - The relationship between the presence and types of integrons and the
      antimicrobial susceptibility patterns of Acinetobacter baumannii was
      investigated. A total of 134 non-duplicated A. baumannii isolates, 54.5% (n=73)
      of which were subsequently found to carry class 1 integrons, were collected from
      a regional hospital in Taiwan between March and September 2007. Only two types of
      gene cassette array, aacA4-catB8-aadA1 and aacC1-orfP-orfP-orfQ-aadA1, were
      identified. Susceptibility data showed that those strains carrying integrons were
      significantly more resistant to all antibiotics tested except
      ampicillin/sulbactam and imipenem. An epidemiological study revealed that the
      same integron could be found in different unrelated strains. These findings
      suggest that the presence of integrons in A. baumannii is responsible for both
      the horizontal transfer of antibiotic-resistance genes related to aminoglycosides
      and chloramphenicol and also represents a marker of multidrug resistance and
      epidemic potential.

PMID- 21099098
TI  - Biliary sepsis caused by Ochrobactrum anthropi.
AB  - Ochrobactrum anthropi is an emerging pathogen in immunocompromised patients, with
      the majority of human cases being central venous catheter-related infections. In
      contrast, O. anthropi-related biliary sepsis is much rare. Herein we report the
      clinical and microbiological characteristics of O. anthropi-related biliary
      sepsis in order to increase awareness of the potential role of O. anthropi in
      this infection. Further extensive epidemiologic studies should be carried out to
      ascertain the etiologic association between O. anthropi and biliary sepsis and to
      identify potential hosts and routes of transmission.

PMID- 21099099
TI  - Ascariasis in Japan: is pig-derived Ascaris infecting humans?
AB  - Human ascariasis is caused by infection with the common roundworm Ascaris
      lumbricoides, although the pig roundworm Ascaris suum has also been reported to
      infect humans and develop into the adult stage. To elucidate whether pig-derived
      Ascaris infects humans in Japan, 9 Ascaris isolates obtained from Japanese
      patients and a further 9 Ascaris isolates of pig origin were analyzed to
      determine their internal transcribed spacer-1 sequences. Six of the 9 clinical
      isolates showed the Ascaris genotype which predominantly infects humans in
      endemic countries, while the other 3 clinical isolates and 9 pig-derived isolates
      showed the genotype predominant in pigs worldwide. These results suggest that at
      least some cases of human ascariasis in Japan are a result of infection with pig
      derived Ascaris.

PMID- 21099100
TI  - Frequent isolation of Echinococcus multilocularis from the livers of racehorses
      slaughtered in Yamagata, Japan.

PMID- 21099101
TI  - Integral role of integrins in Th17 development.
AB  - A lineage of CD4+ T cells known as Th17 cells, which are derived by exposure of
      naive CD4+ T cells to IL-6 and TGF-beta, have been implicated in several
      autoimmune diseases. In this issue of the JCI, studies by Acharya et al. and
      Melton et al. show that TGF-beta is activated at the DC/CD4+ T cell synapse by
      alphav integrins and that this activation is required for Th17 differentiation
      and autoimmunity in the central nervous system. Thus, these studies offer a
      potential therapeutic target in fighting autoimmune diseases.

PMID- 21099102
TI  - Can TNF-alpha boost regulatory T cells?
AB  - Deleterious immune responses that cause autoimmune diseases such as type 1
      diabetes are normally kept in check by a myriad of mechanisms. Among these,
      protection mediated by CD4+Foxp3+ Tregs constitutes an essential pathway. Much
      work over the past decade aimed to understand how Tregs affect immune responses
      triggered by effector T cells (Teffs), but less is known about how Teffs affect
      Tregs. In this issue of the JCI, Grinberg-Bleyer et al. report the clearest
      example thus far regarding this important aspect of Treg biology. They find that
      in mice, sustained protection from diabetes by Tregs is dependent on Teffs and
      partially dependent on TNF-alpha, a cytokine traditionally considered
      proinflammatory.

PMID- 21099103
TI  - The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer?
AB  - The retinoblastoma tumor suppressor gene (RB1; encoding RB) is often cited as a
      gatekeeper, whose inactivation - direct or indirect - is a rate-limiting step for
      tumor initiation. However, in this issue of the JCI, Sharma et al. show that RB1
      loss is a late event in human prostate cancer that is coincident with the
      emergence of castrate-resistant metastatic disease. This role for RB1 was linked
      to both E2F transcription factor 1-driven upregulation of the androgen receptor
      (AR) and increased recruitment of the AR to target gene promoters. This
      unexpected function for RB1 in late-stage cancer calls upon us to reassess the
      significance of RB1 inactivation in other cancers in terms of its timing,
      function in disease etiology, and relevance for cancer therapy.

PMID- 21099104
TI  - Which species are in your feces?
AB  - Nosocomial infections (i.e., infections acquired as a result of treatment in a
      hospital or health care unit) result in approximately 100,000 deaths and cost
      more than 25 billion dollars per year in the US alone. These infections are
      caused primarily by bacteria and affect mainly immunosuppressed patients.
      However, not all patients acquire infections, and the events leading up to
      infection are unclear. In this issue of the JCI, Ubeda et al. report how
      acquisition of one such infection, vancomycin-resistant Enterococcus faecium
      (VRE), is linked to a shift in the microbial flora following antibiotic
      treatment. This study highlights the potential for high-throughput sequencing of
      intestinal microbiota as a means to identify high-risk populations.

PMID- 21099105
TI  - A tincture of hepcidin cures all: the potential for hepcidin therapeutics.
AB  - Iron overload as a result of blood transfusions and excessive intestinal iron
      absorption can be a complication of chronic anemias such as beta-thalassemia.
      Inappropriately low levels of hepcidin, a negative regulator of iron absorption
      and recycling, underlie the pathophysiology of the intestinal hyperabsorption. In
      this issue of the JCI, Gardenghi et al. demonstrate that increasing hepcidin
      expression to induce iron deficiency in murine beta-thalassemia not only
      mitigates the iron overload, but also the severity of the anemia. These data
      illustrate the therapeutic potential of modulating hepcidin expression in
      diseases associated with altered iron metabolism.

PMID- 21099106
TI  - Learning about genomics and disease from the anucleate human red blood cell.
AB  - During the differentiation of an erythrocyte, the developing erythroblast shuts
      down expression of most of its genes but preserves high levels of expression of
      certain key genes, such as those encoding hemoglobin and critical membrane
      proteins. In this issue of the JCI, Gallagher et al. show that a specialized type
      of DNA sequence element known as an insulator protects the expression of ankyrin,
      a key membrane protein. In several kindreds, mutations in the insulator led to
      impaired ankyrin expression and congenital hemolytic anemia. This work provides
      important insights into ways in which epigenetic changes can alter gene
      expression and thereby lead to human disease.

PMID- 21099107
TI  - Can we build it better? Using BAC genetics to engineer more effective
      cytomegalovirus vaccines.
AB  - The magnitude and durability of immunity to human cytomegalovirus (HCMV)
      following natural infection is compromised by the presence of immune modulation
      genes that appear to promote evasion of host clearance mechanisms. Since immunity
      to HCMV offers limited protection, rational design of effective vaccines has been
      challenging. In this issue of the JCI, Slavuljica and colleagues employ
      techniques to genetically modify the highly related mouse CMV (MCMV), in the
      process generating a virus that was rapidly cleared by NK cells. The virus
      functioned as a safe and highly effective vaccine. Demonstration of the ability
      to engineer a safe and highly effective live virus vaccine in a relevant rodent
      model of CMV infection may open the door to clinical trials of safer and more
      immunogenic HCMV vaccines.

PMID- 21099108
TI  - LFA-1-specific therapy prolongs allograft survival in rhesus macaques.
AB  - Outcomes in transplantation have been limited by suboptimal long-term graft
      survival and toxicities associated with current immunosuppressive approaches. T
      cell costimulation blockade has shown promise as an alternative strategy to avoid
      the side effects of conventional immunosuppressive therapies, but targeting CD28
      mediated costimulation alone has proven insufficient to prevent graft rejection
      in primates. Donor-specific memory T (TM) cells have been implicated in
      costimulation blockade-resistant transplant rejection, due to their enhanced
      effector function and decreased reliance on costimulatory signaling. Thus, we
      have tested a potential strategy to overcome TM cell-driven rejection by
      targeting molecules preferentially expressed on these cells, such as the adhesion
      molecule lymphocyte function-associated antigen 1 (LFA-1). Here, we show that
      short-term treatment (i.e., induction therapy) with the LFA-1-specific antibody
      TS-1/22 in combination with either basiliximab (an IL-2Ralpha-specific mAb) and
      sirolimus (a mammalian target of rapamycin inhibitor) or belatacept (a high
      affinity variant of the CD28 costimulation-blocker CTLA4Ig) prolonged islet
      allograft survival in nonhuman primates relative to control treatments. Moreover,
      TS-1/22 masked LFA-1 on TM cells in vivo and inhibited the generation of
      alloproliferative and cytokine-producing effector T cells that expressed high
      levels of LFA-1 in vitro. These results support the use of LFA-1-specific
      induction therapy to neutralize costimulation blockade-resistant populations of T
      cells and further evaluation of LFA-1-specific therapeutics for use in
      transplantation.

PMID- 21099109
TI  - Mutation of a barrier insulator in the human ankyrin-1 gene is associated with
      hereditary spherocytosis.
AB  - Defects of the ankyrin-1 gene are the most common cause in humans of hereditary
      spherocytosis, an inherited anemia that affects patients of all ethnic groups. In
      some kindreds, linked -108/-153 nucleotide substitutions have been found in the
      upstream region of the ankyrin gene promoter that is active in erythroid cells.
      In vivo, the ankyrin erythroid promoter and its upstream region direct position
      independent, uniform expression, a property of barrier insulators. Using human
      erythroid cell lines and primary cells and transgenic mice, here we have
      demonstrated that a region upstream of the erythroid promoter is a barrier
      insulator in vivo in erythroid cells. The region exhibited both functional and
      structural characteristics of a barrier, including prevention of gene silencing
      in an in vivo functional assay, appropriate chromatin configuration, and
      occupancy by barrier-associated proteins. Fragments with the -108/-153
      spherocytosis-associated mutations failed to function as barrier insulators in
      vivo and demonstrated perturbations in barrier-associated chromatin
      configuration. In transgenic mice, flanking a mutant -108/-153 ankyrin gene
      promoter with the well-characterized chicken HS4 barrier insulator restored
      position-independent, uniform expression at levels comparable to wild-type. These
      data indicate that an upstream region of the ankyrin-1 erythroid promoter acts as
      a barrier insulator and identify disruption of the barrier element as a potential
      pathogenetic mechanism of human disease.

PMID- 21099110
TI  - The retinoblastoma tumor suppressor controls androgen signaling and human
      prostate cancer progression.
AB  - Retinoblastoma (RB; encoded by RB1) is a tumor suppressor that is frequently
      disrupted in tumorigenesis and acts in multiple cell types to suppress cell cycle
      progression. The role of RB in tumor progression, however, is poorly defined.
      Here, we have identified a critical role for RB in protecting against tumor
      progression through regulation of targets distinct from cell cycle control. In
      analyses of human prostate cancer samples, RB loss was infrequently observed in
      primary disease and was predominantly associated with transition to the
      incurable, castration-resistant state. Further analyses revealed that loss of the
      RB1 locus may be a major mechanism of RB disruption and that loss of RB function
      was associated with poor clinical outcome. Modeling of RB dysfunction in vitro
      and in vivo revealed that RB controlled nuclear receptor networks critical for
      tumor progression and that it did so via E2F transcription factor 1-mediated
      regulation of androgen receptor (AR) expression and output. Through this pathway,
      RB depletion induced unchecked AR activity that underpinned therapeutic bypass
      and tumor progression. In agreement with these findings, disruption of the
      RB/E2F/nuclear receptor axis was frequently observed in the transition to therapy
      resistance in human disease. Together, these data reveal what we believe to be a
      new paradigm for RB function in controlling prostate tumor progression and lethal
      tumor phenotypes.

PMID- 21099111
TI  - Recombinant mouse cytomegalovirus expressing a ligand for the NKG2D receptor is
      attenuated and has improved vaccine properties.
AB  - Human CMV (HCMV) is a major cause of morbidity and mortality in both congenitally
      infected and immunocompromised individuals. Development of an effective HCMV
      vaccine would help protect these vulnerable groups. NK group 2, member D (NKG2D)
      is a potent activating receptor expressed by cells of the innate and adaptive
      immune systems. Its importance in HCMV immune surveillance is indicated by the
      elaborative evasion mechanisms evolved by the virus to avoid NKG2D. In order to
      study this signaling pathway, we engineered a recombinant mouse CMV expressing
      the high-affinity NKG2D ligand RAE-1gamma (RAE-1gammaMCMV). Expression of RAE
      1gamma by MCMV resulted in profound virus attenuation in vivo and lower latent
      viral DNA loads. RAE-1gammaMCMV infection was efficiently controlled by
      immunodeficient hosts, including mice lacking type I interferon receptors or
      immunosuppressed by sublethal gamma-irradiation. Features of MCMV infection in
      neonates were also diminished. Despite tight innate immune control, RAE
      1gammaMCMV infection elicited strong and long-lasting protective immunity.
      Maternal RAE-1gammaMCMV immunization protected neonatal mice from MCMV disease
      via placental transfer of antiviral Abs. Despite strong selective pressure, the
      RAE-1gamma transgene did not exhibit sequence variation following infection.
      Together, our results indicate that use of a recombinant virus encoding the
      ligand for an activating NK cell receptor could be a powerful approach to
      developing a safe and immunogenic HCMV vaccine.

PMID- 21099112
TI  - Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta
      thalassemic mice.
AB  - Excessive iron absorption is one of the main features of beta-thalassemia and can
      lead to severe morbidity and mortality. Serial analyses of beta-thalassemic mice
      indicate that while hemoglobin levels decrease over time, the concentration of
      iron in the liver, spleen, and kidneys markedly increases. Iron overload is
      associated with low levels of hepcidin, a peptide that regulates iron metabolism
      by triggering degradation of ferroportin, an iron-transport protein localized on
      absorptive enterocytes as well as hepatocytes and macrophages. Patients with beta
      thalassemia also have low hepcidin levels. These observations led us to
      hypothesize that more iron is absorbed in beta-thalassemia than is required for
      erythropoiesis and that increasing the concentration of hepcidin in the body of
      such patients might be therapeutic, limiting iron overload. Here we demonstrate
      that a moderate increase in expression of hepcidin in beta-thalassemic mice
      limits iron overload, decreases formation of insoluble membrane-bound globins and
      reactive oxygen species, and improves anemia. Mice with increased hepcidin
      expression also demonstrated an increase in the lifespan of their red cells,
      reversal of ineffective erythropoiesis and splenomegaly, and an increase in total
      hemoglobin levels. These data led us to suggest that therapeutics that could
      increase hepcidin levels or act as hepcidin agonists might help treat the
      abnormal iron absorption in individuals with beta-thalassemia and related
      disorders.

PMID- 21099113
TI  - Pathogenic T cells have a paradoxical protective effect in murine autoimmune
      diabetes by boosting Tregs.
AB  - CD4+CD25+Foxp3+ Tregs play a major role in prevention of autoimmune diseases. The
      suppressive effect of Tregs on effector T cells (Teffs), the cells that can
      mediate autoimmunity, has been extensively studied. However, the in vivo impact
      of Teff activation on Tregs during autoimmunity has not been explored. In this
      study, we have shown that CD4+ Teff activation strongly boosts the expansion and
      suppressive activity of Tregs. This helper function of CD4+ T cells, which we
      believe to be novel, was observed in the pancreas and draining lymph nodes in
      mouse recipients of islet-specific Teffs and Tregs. Its physiological impact was
      assessed in autoimmune diabetes. When islet-specific Teffs were transferred
      alone, they induced diabetes. Paradoxically, when the same Teffs were
      cotransferred with islet-specific Tregs, they induced disease protection by
      boosting Treg expansion and suppressive function. RNA microarray analyses
      suggested that TNF family members were involved in the Teff-mediated Treg boost.
      In vivo experiments showed that this Treg boost was partially dependent on TNF
      but not on IL-2. This feedback regulatory loop between Teffs and Tregs may be
      critical to preventing or limiting the development of autoimmune diseases.

PMID- 21099114
TI  - alphav Integrin expression by DCs is required for Th17 cell differentiation and
      development of experimental autoimmune encephalomyelitis in mice.
AB  - Th17 cells are a distinct lineage of T helper cells that protect the body from
      bacterial and fungal infection. However, Th17 cells also contribute to
      inflammatory and autoimmune disorders such as multiple sclerosis. Th17 cell
      generation requires exposure of naive T cells to the cytokine TGF-beta in
      combination with proinflammatory cytokines. Here we show that differentiation of
      Th17 cells is also critically dependent on alphav integrins. In mice, lack of
      integrin alphav in the immune system resulted in loss of Th17 cells in the
      intestine and lymphoid tissues. It also led to protection from experimental
      autoimmune encephalomyelitis (EAE). Further analysis indicated that alphav
      integrins on DCs activated latent TGF-beta during T cell stimulation and thereby
      promoted differentiation of Th17 cells. Furthermore, pharmacologic inhibition of
      alphav integrins using cyclic RGD peptides blocked TGF-beta activation and Th17
      cell generation in vitro and protected mice from EAE. These data demonstrate that
      activation of TGF-beta by alphav-expressing myeloid cells may be a critical step
      in the generation of Th17 cells and suggest that alphav integrins could be
      therapeutic targets in autoimmune disease.

PMID- 21099115
TI  - Role of chronic ryanodine receptor phosphorylation in heart failure and beta
      adrenergic receptor blockade in mice.
AB  - Increased sarcoplasmic reticulum (SR) Ca2+ leak via the cardiac ryanodine
      receptor/calcium release channel (RyR2) is thought to play a role in heart
      failure (HF) progression. Inhibition of this leak is an emerging therapeutic
      strategy. To explore the role of chronic PKA phosphorylation of RyR2 in HF
      pathogenesis and treatment, we generated a knockin mouse with aspartic acid
      replacing serine 2808 (mice are referred to herein as RyR2-S2808D+/+ mice). This
      mutation mimics constitutive PKA hyperphosphorylation of RyR2, which causes
      depletion of the stabilizing subunit FKBP12.6 (also known as calstabin2),
      resulting in leaky RyR2. RyR2-S2808D+/+ mice developed age-dependent
      cardiomyopathy, elevated RyR2 oxidation and nitrosylation, reduced SR Ca2+ store
      content, and increased diastolic SR Ca2+ leak. After myocardial infarction, RyR2
      S2808D+/+ mice exhibited increased mortality compared with WT littermates.
      Treatment with S107, a 1,4-benzothiazepine derivative that stabilizes RyR2
      calstabin2 interactions, inhibited the RyR2-mediated diastolic SR Ca2+ leak and
      reduced HF progression in WT and RyR2-S2808D+/+ mice. In contrast, beta
      adrenergic receptor blockers improved cardiac function in WT but not in RyR2
      S2808D+/+ mice.Thus, chronic PKA hyperphosphorylation of RyR2 results in a
      diastolic leak that causes cardiac dysfunction. Reversing PKA
      hyperphosphorylation of RyR2 is an important mechanism underlying the therapeutic
      action of beta-blocker therapy in HF.

PMID- 21099116
TI  - Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled
      by antibiotic treatment in mice and precedes bloodstream invasion in humans.
AB  - Bloodstream infection by highly antibiotic-resistant bacteria, such as vancomycin
      resistant Enterococcus (VRE), is a growing clinical problem that increasingly
      defies medical intervention. Identifying patients at high risk for bacterial
      sepsis remains an important clinical challenge. Recent studies have shown that
      antibiotics can alter microbial diversity in the intestine. Here, we
      characterized these effects using 16s rDNA pyrosequencing and demonstrated that
      antibiotic treatment of mice enabled exogenously administered VRE to efficiently
      and nearly completely displace the normal microbiota of the small and large
      intestine. In the clinical setting, we found that intestinal domination by VRE
      preceded bloodstream infection in patients undergoing allogeneic hematopoietic
      stem cell transplantation. Our results demonstrate that antibiotics perturb the
      normal commensal microbiota and set the stage for intestinal domination by
      bacteria associated with hospital-acquired infections. Thus, high-throughput DNA
      sequencing of the intestinal microbiota could identify patients at high risk of
      developing bacterial sepsis.

PMID- 21099117
TI  - Expression of alphavbeta8 integrin on dendritic cells regulates Th17 cell
      development and experimental autoimmune encephalomyelitis in mice.
AB  - Th17 cells promote a variety of autoimmune diseases, including psoriasis,
      multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TGF
      beta is required for conversion of naive T cells to Th17 cells, but the
      mechanisms regulating this process are unknown. Integrin alphavbeta8 on DCs can
      activate TGF-beta, and this process contributes to the development of induced
      Tregs. Here, we have now shown that integrin alphavbeta8 expression on DCs plays
      a critical role in the differentiation of Th17 cells. Th17 cells were nearly
      absent in the colons of mice lacking alphavbeta8 expression on DCs. In addition,
      these mice and the DCs harvested from them had an impaired ability to convert
      naive T cells into Th17 cells in vivo and in vitro, respectively. Importantly,
      mice lacking alphavbeta8 on DCs showed near-complete protection from experimental
      autoimmune encephalomyelitis. Our results therefore suggest that the integrin
      alphavbeta8 pathway is biologically important and that alphavbeta8 expression on
      DCs could be a therapeutic target for the treatment of Th17-driven autoimmune
      disease.

PMID- 21099118
TI  - Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight
      response in mice.
AB  - During the classic "fight-or-flight" stress response, sympathetic nervous system
      activation leads to catecholamine release, which increases heart rate and
      contractility, resulting in enhanced cardiac output. Catecholamines bind to beta
      adrenergic receptors, causing cAMP generation and activation of PKA, which
      phosphorylates multiple targets in cardiac muscle, including the cardiac
      ryanodine receptor/calcium release channel (RyR2) required for muscle
      contraction. PKA phosphorylation of RyR2 enhances channel activity by sensitizing
      the channel to cytosolic calcium (Ca2+). Here, we found that mice harboring RyR2
      channels that cannot be PKA phosphorylated (referred to herein as RyR2-S2808A+/+
      mice) exhibited blunted heart rate and cardiac contractile responses to
      catecholamines (isoproterenol). The isoproterenol-induced enhancement of
      ventricular myocyte Ca2+ transients and fractional shortening (contraction) and
      the spontaneous beating rate of sinoatrial nodal cells were all blunted in RyR2
      S2808A+/+ mice. The blunted cardiac response to catecholamines in RyR2-S2808A+/+
      mice resulted in impaired exercise capacity. RyR2-S2808A+/+ mice were protected
      against chronic catecholaminergic-induced cardiac dysfunction. These studies
      identify what we believe to be new roles for PKA phosphorylation of RyR2 in both
      the heart rate and contractile responses to acute catecholaminergic stimulation.

PMID- 21099119
TI  - Is ryanodine receptor phosphorylation key to the fight or flight response and
      heart failure?
AB  - In situations of stress the heart beats faster and stronger. According to Marks
      and colleagues, this response is, to a large extent, the consequence of
      facilitated Ca2+ release from intracellular Ca2+ stores via ryanodine receptor 2
      (RyR2), thought to be due to catecholamine-induced increases in RyR2
      phosphorylation at serine 2808 (S2808). If catecholamine stimulation is sustained
      (for example, as occurs in heart failure), RyR2 becomes hyperphosphorylated and
      "leaky," leading to arrhythmias and other pathology. This "leaky RyR2 hypothesis"
      is highly controversial. In this issue of the JCI, Marks and colleagues report on
      two new mouse lines with mutations in S2808 that provide strong evidence
      supporting their theory. Moreover, the experiments revealed an influence of redox
      modifications of RyR2 that may account for some discrepancies in the field.

PMID- 21099120
TI  - Validation of longitudinal peak systolic strain by speckle tracking
      echocardiography with visual assessment and myocardial perfusion SPECT in
      patients with regional asynergy.
AB  - BACKGROUND: Automated function imaging (AFI) is a recently developed method of
      calculating the longitudinal peak systolic strains (LS) of the regional left
      ventricular (LV) wall using speckle tracking echocardiography and displaying them
      on a single bull's-eye map. The feasibility of AFI in patients with regional LV
      wall motion abnormalities caused by myocardial infarction (MI) was evaluated by
      comparison with visual assessment and myocardial perfusion single-photon emission
      computed tomography (SPECT). METHODS AND RESULTS: Segmental LS was measured by
      AFI in 60 patients with MI (67 +/- 11 years) and 58 controls (71 +/- 9 years).
      Wall thickening (WT) was measured by SPECT in 20 patients with MI. There was a
      strong positive linear relationship between the wall motion score index by expert
      visual assessment and global LS. The receiver-operating characteristic analysis
      revealed the best cutoff value of 11% < LS to identify hypokinetic segments. The
      overall accuracy of wall motion scoring by LS in the 2,006 segments was 96.8%
      (kappa = 0.90) compared with visual assessment. The correlation coefficient
      between LS and WT was R2 = 0.65 in the 340 segments. CONCLUSIONS: Assessment of
      LV regional asynergy by AFI showed good agreement with visual and SPECT
      assessments. AFI is clinically useful for quantitative assessment of LV regional
      wall motion abnormalities.

PMID- 21099121
TI  - Impact of cytochrome P450 2C19*2 polymorphism on intra-stent thrombus after drug
      eluting stent implantation in Japanese patients receiving clopidogrel.
AB  - BACKGROUND:  The cytochrome P450 (CYP) 2C19*2 polymorphism is associated with
      reduced responsiveness to clopidogrel and poor clinical outcome after stent
      implantation. Despite the high frequency of this polymorphism in Japanese
      patients, its contribution to cardiac events and stent thrombi after drug-eluting
      stent (DES) implantation is not clear in this population. METHODS AND RESULTS: 
      One hundred Japanese patients received clopidogrel and underwent follow-up
      optical coherence tomography (OCT) after DES implantation. The patients were
      divided into 2 groups: those with at least one CYP2C19*2 allele (*2 carriers) and
      non-carriers. The incidence of stent thrombosis and major adverse cardiac events
      (MACE; ie, death, myocardial infarction, and target vessel revascularization) was
      compared between the 2 groups. In addition, OCT was used to evaluate the
      incidence of intra-stent thrombus, defined as a mass protruding into the lumen
      with significant attenuation. Of the 100 patients, 42 were *2 carriers. No
      remarkable differences in the baseline characteristics were noted. Although MACE
      did not differ significantly between the 2 groups, a subclinical intra-stent
      thrombus was detected more frequently in *2 carriers than in non-carriers (52.3%
      vs. 15.5%, P=0.0002). Multivariate logistic regression analysis showed that the
      presence of the CYP2C19*2 polymorphism was the only independent predictive factor
      for intra-stent thrombus (P=0.00006). CONCLUSIONS:  From these results it is
      suggested that CYP2C19*2 polymorphism is associated with subclinical thrombus
      formation among Japanese patients receiving clopidogrel. (Circ J 2011; 75: 99
      105).

PMID- 21099122
TI  - Preprocedural evaluation and endovascular treatment of iliofemoral artery disease
      without contrast media for patients with pre-existing renal insufficiency.
AB  - BACKGROUND: Generally, both the preprocedural evaluation and endovascular therapy
      (EVT) for lower limb arteries require contrast media that is harmful for patients
      with chronic renal insufficiency. In the present study these procedures were
      performed without using nephrotoxic contrast media in patients with preexisting
      renal insufficiency and iliofemoral artery disease. METHODS AND RESULTS: The 36
      consecutive patients with chronic renal insufficiency underwent preprocedural
      evaluation with duplex examination, magnetic resonance angiography (MRA) without
      contrast media, and plain computed tomography (CT). A total of 51 lesions were
      treated using intravascular ultrasound (IVUS) without contrast media. The overall
      technical success was 100% without any complications. Pre- and postprocedural
      ankle-brachial indices changed from 0.59 +/- 0.23 to 0.92 +/- 0.14. The mean
      serum creatinine concentration before and after treatment, and 3 months after
      treatment did not change (2.1 +/- 1.4, 2.0 +/- 1.4, and 2.1 +/- 1.6 mg/dl,
      respectively). The overall 3-month survival rate and limb salvage rate was 100%.
      CONCLUSIONS: EVT comprising duplex, MRA, and CT for preprocedural evaluation and
      IVUS-guided procedure is feasible and may avoid intra-arterial contrast injection
      in selected patients deemed at high risk for renal failure from nephrotoxic
      contrast material.

PMID- 21099123
TI  - Left ventricular basal myocardial scarring detected by delayed enhancement
      magnetic resonance imaging predicts outcomes after surgical therapies for
      patients with ischemic mitral regurgitation and left ventricular dysfunction.
AB  - BACKGROUND: Treatment of heart failure by surgical procedures such as mitral
      annuloplasty and left ventricular (LV) restoration is increasingly applied to
      patients with ischemic mitral regurgitation (IMR) and LV dysfunction. The
      clinical efficacy of delayed enhancement magnetic resonance imaging (DE-MRI) was
      studied to predict LV functional recovery and adverse outcomes after these
      therapies. METHODS AND RESULTS: In 26 patients with IMR and a LV ejection
      fraction < 40%, DE-MRI was performed before the operation and the percentage of
      regional myocardial scarring was quantified at the basal, mid, and apical LV.
      Calculated percentage of fibrosis was 12 +/- 12% at the base, 24 +/- 15% at the
      mid, and 35 +/- 31% at the apical LV. The degree of basal fibrosis was a
      significant predictor of less improvement of LV ejection fraction and
      postoperative restrictive diastolic filling. A linear correlation was noted
      between basal fibrosis and postoperative ejection fraction (P = 0.001, R = 
      0.61), the early to late mitral valve flow ratio (P = 0.0005, R = 0.66), and
      deceleration time (P = 0.01, R = -0.51). Logistic regression analysis
      demonstrated that the percentage of basal fibrosis was the independent predictor
      of postoperative adverse clinical outcomes (odds ratio, 1.26; P = 0.04).
      CONCLUSIONS: In patients undergoing surgical heart failure therapy for IMR, the
      extent of basal fibrosis characterized by DE-MRI might be a useful predictor of
      postoperative LV systolic and diastolic functional recovery and postoperative
      adverse outcomes.

PMID- 21099124
TI  - Painless acute aortic dissection. - Diagnostic, prognostic and clinical
      implications.-.
AB  - BACKGROUND: Acute aortic dissection (AAD) classically presents as sudden, severe
      chest, back, or abdominal pain. However, there have been several documented cases
      presenting with atypical features. The clinical characteristics and outcomes of
      patients with painless AAD were investigated. METHODS AND RESULTS: The study
      group comprised 98 patients (53 males, 45 females; 66 +/- 12 years) with AAD
      admitted to hospital from 2002 to 2007: 16 patients (17%) had no pain (painless
      group) and 82 patients had pain (painful group). In 81% of the painless group and
      70% of the painful group there was a type A dissection. The painless group more
      frequently had a persistent disturbance of consciousness (44% vs. 6%, P < 0.001),
      syncope (25% vs. 1%, P < 0.001) and a focal neurologic deficit (19% vs. 2%, P =
      0.006) as presenting symptoms. Imaging study findings were not significantly
      different. Cerebral ischemia (50% vs. 1%, P < 0.001) and cardiac tamponade (38%
      vs. 13%, P = 0.01) were more frequent complications in the painless group. In
      hospital mortality was not significantly different (19% vs. 15%). However, the
      painless group had a more unfavorable functional outcome on overall performance
      category (P < 0.001). CONCLUSIONS: Painless AAD may be more frequent than
      previously reported. Painless AAD patients often present with a disturbance of
      consciousness or a neurologic deficit, and have a higher morbidity than painful
      AAD patients.

PMID- 21099125
TI  - Transmural dispersion of repolarization determines scroll wave behavior during
      ventricular tachyarrhythmias.
AB  - BACKGROUND: Ventricular tachyarrhythmia is the leading cause of sudden cardiac
      death, and scroll wave re-entry is known to underlie this condition. Class III
      antiarrhythmic drugs are commonly used worldwide to treat ventricular
      tachyarrhythmias; however, these drugs have a proarrhythmic adverse effect and
      can cause Torsade de Pointes or ventricular fibrillation. Transmural dispersion
      of repolarization (TDR) has been suggested to be a strong indicator of
      ventricular tachyarrhythmia induction. However, the role of TDR during sustained
      scroll wave re-entry is poorly understood. The purpose of the present study was
      to investigate how TDR affects scroll wave behavior and to provide a novel
      analysis of the mechanisms that sustain tachyarrhythmias, using computer
      simulations. METHODS AND RESULTS: Computer simulations were carried out to
      quantify the TDR and QT interval under a variety of I(Ks) and I(Kr) during
      transmural conduction. Simulated scroll wave re-entries were done under a variety
      of I(Ks) and I(Kr) in a ventricular wall slab model, and the scroll wave behavior
      and the filament dynamics (3-dimensional organizing center) were analyzed. A
      slight increase in TDR, but not in the QT interval, reflected antiarrhythmic
      properties resulting from the restraint of scroll wave breakup, whereas a marked
      increase in TDR was proarrhythmic, as a result of scroll wave breakup.
      CONCLUSIONS: The TDR determines the sustainment of ventricular tachyarrhythmias,
      through control of the scroll wave filament dynamics.

PMID- 21099126
TI  - Progression rate from new-onset pre-hypertension to hypertension in Korean
      adults.
AB  - BACKGROUND: There are limited studies conducted in Asia to investigate the
      progression rate to hypertension (HTN). This study was done to estimate the
      progression rate of new-onset pre-HTN (PreHTN) to HTN during an 8-year follow-up
      period, and to compare the impact of PreHTN on progression to HTN. METHODS AND
      RESULTS: A total of 49,228 participants, aged 30 to 54 years with new-onset
      PreHTN at baseline (1994-1996) from a biennial national medical exam were
      enrolled and followed up every 2 years until 2004. The incidence rate recorded at
      each interval and the cumulative incidence rate of HTN were analyzed. Hazard
      ratio of high-normal and high blood pressure (BP) in men and women was
      calculated. The cumulative incidence rate for high-normal BP was 27.6% and 26.4%
      at 2-year follow-up, increased to respectively 64.1% and 55.8% in men and women
      at the 8-year follow-up. Compared to optimal BP, hazard ratios for men with high
      normal BP across all age groups were 3- to 4-fold higher at 2-year, and 2- to 3
      fold higher at 8-year follow-up. Hazard ratios for women were about 6-fold higher
      at 2-year and around 4-fold higher at 8-year follow-up. CONCLUSIONS: New PreHTN
      was a significant predisposing factor for future HTN, in young adults and the
      effect is more prominent in women.

PMID- 21099127
TI  - Prediction of chronic renal insufficiency after coronary angiography by an early
      increase in oxidative stress and decrease in glomerular filtration rate.
AB  - BACKGROUND: Oxidative stress caused by contrast medium is thought to be one of
      the main mechanisms of contrast-induced acute kidney injury. A prospective study
      was conducted to evaluate the relationship between oxidative stress caused by
      contrast agent administration and long-term renal function. METHODS AND RESULTS:
      Thirty-six consecutive patients who underwent coronary angiography were enrolled.
      Urinary F2-isoprostane, a marker of oxidative stress, was measured at baseline
      and 24h after angiography, and serum creatinine was measured at baseline, 24h and
      1 year after the procedure. The change in estimated glomerular filtration rate
      (eGFR) at 1 year after angiography correlated significantly with the change in
      eGFR at 24h after angiography (r=0.729, P<0.001). We also found a significant
      correlation between the increase in urinary F2-isoprostane at 24h and the
      decrease in eGFR at 1 year (r=0.439, P=0.022). In multivariate analysis, the
      decrease in eGFR at 1 year after coronary angiography correlated with the
      increase in F2-isoprostane at 24h after angiography as well as the decrease in
      eGFR at 24h after angiography (P=0.039 and P<0.001, respectively). CONCLUSIONS:
      Contrast-induced nephrotoxicity might be transient; however, an early decrease in
      eGFR and increase in oxidative stress are associated with chronic renal
      insufficiency. Careful long-term follow-up and adequate medical intervention are
      necessary for these patients.

PMID- 21099128
TI  - A solid thyroid benign nodule that showed a significant decrease in size and
      ultrasonographic findings mimicking papillary carcinoma during 16-year follow-up.
AB  - Recent advances in ultrasonography and fine needle aspiration biopsy (FNAB) have
      facilitated accurate diagnosis of thyroid carcinomas that require treatment.
      However, we often encounter nodules evaluated as malignant on ultrasonography but
      diagnosed as benign on cytology, for which the optimal treatment strategy remains
      uncertain. A 28-year-old female had solitary and solid thyroid nodule measuring 6
      cm in maximal diameter in February 1994. The lesion was cytologically diagnosed
      as benign. From September 1998, the nodule spontaneously decreased in size but
      ultrasonographic findings suspicious of malignancy such as peripheral and intra
      tumoral calcification, low internal echo and irregular border gradually appeared.
      In July 2010, the volume of her nodule showed 97% decrease but was evaluated as
      papillary carcinoma on ultrasonography. FNAB was performed again and the nodule
      was diagnosed as benign. When we encounter a nodule showing ultrasonographic
      findings suggestive of malignancy with negative cytology, we should consider the
      possibility of a benign nodule degenerating over time.

PMID- 21099129
TI  - Effect of presurgical long-acting octreotide treatment in acromegaly patients
      with invasive pituitary macroadenomas: a prospective randomized study.
AB  - Therapeutic effects of presurgical long-acting octreotide treatment on tumor
      shrinkage, and short- and long-term postoperative GH and IGF-1 levels of
      acromegaly patients with invasive pituitary macroadenomas were investigated
      prospectively in Huashan Hospital, Shanghai, China. Thirty-nine untreated
      acromegaly patients, all with invasive pituitary macroadenomas, were randomly
      divided into two groups: experimental group (n=19), and control group (n=20).
      Patients in the experimental group received a three-month course of long-acting
      octreotide treatment before transsphenoidal surgery; the control group underwent
      surgery directly. Tumor shrinkage after drug treatment and short- and long-term
      postoperative GH and IGF-1 levels were analyzed in the two groups. Long-acting
      octreotide treatment reduced tumor size from 7893 +/- 6450 to 4794 +/- 4682
      mm(3). Mean shrinkage rate was 37.4 +/- 30.9%. GH and IGF-1 levels of the
      experimental group were lower than the control group at 3 months, 6 months after
      surgery, and after long-term follow-up. Remission rate (both GH and IGF-1 normal)
      of the experimental group was higher at 3 and 6 months follow-up, but exhibited
      no advantage in long-term follow-up. In the experimental group, the total
      resection rate was higher in patients whose Hardy-Knosp grading decreased to <= 2
      than those whose Hardy-Knosp grading is still >= 3 after drug pretreatment. In
      conclusion, presurgical long-acting octreotide treatment effectively reduces
      tumor size and invasion, which helps enhance early remission rates of invasive
      macroadenomas by transsphenoidal surgery, but does not appear to improve the long
      term cure rate.

PMID- 21099130
TI  - Relationships between plasma fatty acid composition and coronary artery disease.
AB  - AIM: The Japan EPA Lipid Intervention Study (JELIS) was the first prospective
      randomized clinical trial to demonstrate prevention of coronary events by pure
      eicosapentaenoic acid (EPA). The aim of this study was to examine the
      relationships between various plasma fatty acid concentrations and the risk of
      coronary events in JELIS participants. METHODS: In 15,534 participants, we
      calculated the hazard ratio for major coronary events (sudden cardiac death,
      fatal or nonfatal myocardial infarction, unstable angina pectoris, and
      angioplasty/stenting or coronary artery bypass grafting) relative to the on
      treatment average level of plasma fatty acids with the Cox proportional hazard
      model. RESULTS: As a result of EPA intervention, the plasma EPA concentration
      increased, but the docosahexaenoic acid (DHA) concentration did not. The other
      fatty acids measured decreased slightly. The higher plasma level of EPA (hazard
      ratio=0.83, p=0.049, in all participants and hazard ratio=0.71, p=0.018, in the
      EPA intervention group), but not of DHA, was inversely associated with the risk
      of major coronary events. The associations between other fatty acids and the risk
      of major coronary events were not significant. In all JELIS participants, the
      risk of major coronary events was significantly decreased (20%) in the group with
      high (150 ug/mL or more) on-treatment plasma EPA concentration compared with that
      in the low (less than 87 ug/mL) group. CONCLUSION: The risk of coronary artery
      disease is influenced by variations in plasma fatty acid composition. Among n-3
      polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation
      with the risk of major coronary events.

PMID- 21099132
TI  - Cadmium biosorption by yeast, Candida tropicalis CBL-1, isolated from industrial
      wastewater.
AB  - The present study is aimed at assessing the ability of metal-resistant yeast,
      Candida tropicalis CBL-1, to uptake metal from liquid medium. The minimum
      inhibitory concentration of Cd(II) against Candida tropicalis CBL-1 was 2,800
      mg/L. The yeast could also tolerate Zn(II) (3,100 mg/L), Hg(II) (2,400 mg/L),
      Ni(II) (2,200 mg/L), Cr(VI) (2,000 mg/L), Pb(II) (1,100 mg/L), and Cu(II) (2,200
      mg/L). The yeast isolate showed typical growth curves but lag and log phases
      extended in the presence of cadmium. The yeast isolate showed optimum growth at
      30oC and pH 7. The metal processing ability of the isolate was determined in a
      medium containing 100 mg/L of Cd(II). Candida tropicalis CBL-1, could reduce
      Cd(II) 59%, 64% and 70% from the medium after 48, 96 and 144 h, respectively. C.
      tropicalis CBL-1 was also able to remove Cd(II) 46% and 60% from the wastewater
      after 6 and 12 days, respectively. Cd produced an increase in glutathione and non
      protein thiols level by 37% (17.50+/-0.8-24.0+/-1.2) and 18% (3.30+/-0.7- 3.90+/
      0.8) at 100 mg/L concentration, respectively. Metal tolerance and accumulation
      together with changes in the GSH status and non-protein thiols under Cd exposure
      were studied in C. tropicalis.

PMID- 21099133
TI  - Identification of moderately halophilic bacteria from Thai fermented fish ( pla
      ra ) and proposal of Virgibacillus siamensis sp. nov.
AB  - Forty-one isolates of moderately halophilic bacteria were isolated from fermented
      fish (pla-ra) in Thailand. On the basis of their phenotypic and chemotaxonomic
      characteristics, DNA-DNA relatedness and 16S rRNA gene sequences analyses, they
      were divided into six groups. The isolates in Group I to V were Gram-positive rod
      shaped bacteria. They contained meso-diaminopimelic acid in the cell-wall
      peptidoglycan and menaquinone with seven isoprene units (MK-7). An isolate in
      Group VI was a Gram-negative rod-shaped bacterium. The DNA G+C contents of tested
      strains ranged from 36.5-63 mol%. Ten strains (Group I) were identified as
      Virgibacillus dokdonensis, 13 isolates (Group II) as V. halodenitrificans, 14
      isolates (Group III) as V. marismortui, 1 isolate (Group IV) as Virgibacillus
      sp., 2 isolates (Group V) as Bacillus vietnamnensis, and 1 isolate (Group VI) as
      Chromohalobacter salexigens. Isolate MS3-4 in Group IV was closely related to V.
      carmonensis KCTC 3819(T) (95.9%). This strain contained anteiso-C(15:0) (55.8%)
      and anteiso-C(17:0) (17.7%) as major cellular fatty acids and had
      phosphatidylglycerol, diphosphatidylglycerol and an unidentified glycolipid as
      polar lipids. The DNA G+C content of MS3-4 was 38.0 mol%. The strain from Group
      IV is proposed as Virgibacillus siamensis sp. nov. and MS3-4(T) is the type
      strain (JCM 15395(T) =PCU 312(T) =TISTR 1957(T)).

PMID- 21099134
TI  - Bioconversion of cinnamic acid derivatives by Schizophyllum commune.
AB  - To investigate the production of useful phenols from plant resources, we examined
      the metabolism of cinnamic acid derivatives by a wood-rotting fungus,
      Schizophyllum commune. Four cinnamic acid derivatives (cinnamic, p-coumaric,
      ferulic, and sinapic acids) were tested as substrates. Two main reactions,
      reduction and cleavage of the side chain, were observed. Reduction of the side
      chain was confirmed in cinnamic acid and p-coumaric acid metabolism. The side
      chain cleavage occurred in p-coumaric acid and ferulic acid metabolism but the
      initial reactions of these acids differed. Sinapic acid was not metabolized by S.
      commune. p-Hydroxybenzaldehyde accumulation was observed in the culture to which
      p-coumaric acid was added. This suggests that S. commune is a useful agent for
      transforming p-coumaric acid into p-hydroxybenzaldehyde.

PMID- 21099135
TI  - Identification of differentially expressed genes in Sulfobacillus sp. TPY grown
      on either elemental sulphur or Fe(2+).
AB  - Sulfobacillus sp. TPY is a moderately thermophilic and acidophilic bacterium
      found in hydrothermal vents in the Pacific Ocean. This bacterium can oxidize
      ferrous sulfate (Fe(2+)) and elemental sulfur (S(0)) under separate conditions.
      We used random arbitrarily primed polymerase chain reaction (RAP-PCR) to screen
      and identify differentially expressed genes from bacteria grown on Fe(2+) or S(0)
      as the energy source. Fifty-five differential cDNA fragments were isolated and
      subjected to single-pass sequencing. Thirty-five fragments were identified as
      orthologs of known genes in the GenBank databases, of which 19 were confirmed to
      be differentially expressed at the transcriptional level by Northern blot
      analysis. Among these 19 genes, 14 genes, including isocitrate dehydrogenase,
      formyltetrahydrofolate deformylase, 3-hydroxybutyryl-CoA dehydrogenase, and GTP
      binding protein, were upregulated in TPY grown on Fe(2+) or downregulated in TPY
      grown on S(0), while five genes such as the outer membrane adhesion-like protein,
      phosphomannomutase, and cysteine desulfurase sufS were upregulated in TPY strain
      grown on S(0) or downregulated in TPY grown on Fe(2+). These altered genes are
      involved in metabolism, osmotic stress, cell membrane alterations, oxidative
      stress, and the regulatory adaptive response. These results will aid our
      understanding of the molecular basis of Fe(2+) or S(0) oxidation by the
      moderately thermophilic and acidophilic bacteria.

PMID- 21099136
TI  - Comparison of Aspergillus niger spore production on Potato Dextrose Agar (PDA)
      and crushed corncob medium.

PMID- 21099137
TI  - CitB mutation increases the alkaline protease productivity in Bacillus subtilis.

PMID- 21099138
TI  - Lindnera wuzhiensis sp. nov., a novel ascomycetous yeast species.

PMID- 21099139
TI  - Cocultivated bacteria can increase or decrease the culture lifetime of Chlorella
      vulgaris.

PMID- 21099140
TI  - Highly unsaturated fatty acid might act as an antioxidant in emulsion system
      oxidized by azo compound.
AB  - Now it is recognized that DHA is oxidatively stable fatty acid compared with
      linoleic acid (LA) in emulsified system, although DHA is oxidatively unstable in
      a bulk system. In fact, an emulsified mixture of DHA and LA behaves as in a bulk
      system, namely the oxidative stability of DHA becomes lower than that of LA.
      Therefore, in this study, tridocosahexaenoate (DDD) and glycerol trilinoleate
      (LLL) were separately emulsified using TritonX-100 as an emulsifier and DDD
      emulsion was mixed with the oxidizing LLL emulsion using a water-soluble radical
      initiator, 2,2'-azobis(2-aminopropane) dihydrochloride. As a result, DHA
      suppressed the oxidation of LA, while DHA was not significantly oxidized. This
      suppression ability was examined using glycerol trieicosapentaenoate, glycerol
      trilinolenate, or glycerol trioleate instead of DDD and it was found that this
      activity was increased with the increasing number of double bonds in the
      structure. Furthermore, the same type of experiment was carried out using a lipid
      soluble radical initiator, 2,2'-azobisisobutyronitrile and the similar result was
      obtained. These results indicated that a highly polyunsaturated fatty acid might
      act as an antioxidant in an emulsion system oxidized by an azo compound.

PMID- 21099141
TI  - Enzymatic preparation of structured oils containing short-chain fatty acids.
AB  - Structured oils prepared by enzymatic transacylation with triacylglycerols (TAGs)
      and various fatty acids (FAs) were characterized. Transacylation with trilaurin
      and saturated FAs (C4:0-C16:0) was performed using Lipozyme RM-IM under standard
      reaction conditions. The structured oils thus produced had transacylation ratios
      of 25-37%, as medium-chain FAs > long-chain FAs > short-chain FAs. This result
      confirmed that short-chain FAs have little reactivity in enzymatic
      transacylation. All prepared oils shared the same composition of TAG molecular
      species, as demonstrated by HPLC analysis, and contained a mixture of mono
      substituted, di-substituted, and non-substituted TAGs. The reaction conditions
      for transacylation with TAGs and short-chain FAs were optimized to improve
      transacylation ratios. The introduction ratios of C4:0, C5:0, and C6:0 into
      trilaurin were increased to 52.4, 42.5, and 34.1%, respectively, by extending the
      reaction time. Transacylation between TAGs and short-chain FAs was further
      examined by using Lipase PL. C4:0 was introduced at 51.1%, the same ratio as for
      Lipozyme RM-IM. When C5:0 and C6:0 were used as the FA substrate, the
      transacylation ratios obtained were 47.7 and 43.4%, respectively, higher than
      those for Lipase RM-IM. Lipase PL is therefore useful for introducing short-chain
      FAs into TAGs.

PMID- 21099142
TI  - Novel gemini cationic surfactants based on N, N-dimethyl fatty hydrazide and 1,3
      dibromopropane: synthesis, evaluation of surface and antimicrobial properties.
AB  - A fatty hydrazide based cationic gemini surfactants, 1,3-bis (N'-acyl-N,N
      dimethylhydrazinium) propane dibromide which possess hydrolyzable amido moieties
      in the lipophilic portions, were prepared by reacting 1,3-bromopropane with N,N
      dimethyl fatty hydrazide. The surface properties were explained and discussed
      based on the effect of their chemical structures. The micelle-forming ability,
      foaming ability, and foam stability were evaluated. The prepared surfactants also
      showed some antimicrobial activity against gram-positive bacteria (Bacillus
      subtilis, Staphylococcus aureus) but they were not active against gram negative
      bacteria (Escherichia coli, P. aeruginosa), yeast (Candida albicans), and molds
      (Aspergillus niger).

PMID- 21099143
TI  - Characterization and antioxidative activities of rare C(50) carotenoids
      sarcinaxanthin, sarcinaxanthin monoglucoside, and sarcinaxanthin diglucoside
      obtained from Micrococcus yunnanensis.
AB  - While screening for antioxidative carotenoids from marine bacteria, we isolated
      and identified sarcinaxanthin and its glucosylated compounds (sarcinaxanthin
      monoglucoside and sarcinaxanthin diglucoside) from a moderately halophilic
      bacterium-Micrococcus yunnanensis strain AOY-1. In the singlet oxygen ((1O2)
      quenching model, the IC(50) values of the antioxidative activities of these
      carotenoids were as follows: sarcinaxanthin , 57 uM; sarcinaxanthin
      monoglucoside, 54 uM; and sarcinaxanthin diglucoside, 74 uM. In addition, the
      complete proton nuclear magnetic resonance (1H NMR) assignments of sarcinaxanthin
      monoglucoside pentaacetate and sarcinaxanthin diglucoside octaacetate, and fast
      atom bombardment mass spectrometry/mass spectrometry (FAB-MS/MS) analyses of
      sarcinaxanthin and sarcinaxanthin monoglucoside are reported for the first time.

PMID- 21099144
TI  - Crystal structure and complexation and fluorescence behaviors of 1,4-bis (9
      anthracenylmethyl) piperazine.
AB  - The crystal structure of the photoinduced electron transfer (PET) fluoroionophore
      (3) was clarified by X-ray crystallographic analysis. A molecule 3 sits on a
      center of symmetry such that two anthracene ring systems are in an anti
      conformation with respect to one another across the piperazine ring.
      Intermolecular C-H...pi and pi...pi interactions are observed. It was found that
      3 was displayed unique photophysical properties in the presence of guest cations.
      Complexation of 3 with Zn2+ and NH4+ increased the fluorescence intensities of
      the host by a factor of 20.

PMID- 21099145
TI  - Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters
      nanoemulsion.
AB  - Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the
      treatment of various kinds of pains, inflammation and arthritis. However, oral
      administration of ketoprofen produces serious gastrointestinal adverse effects.
      One of the promising methods to overcome these adverse effects is to administer
      the drug through the skin. The aim of the present work is to evaluate the anti
      inflammatory and analgesic effects from topically applied ketoprofen entrapped
      palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen
      product, Fastum((r)) gel. The novelty of this study is, use of POEs for the oil
      phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed
      on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced
      hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based
      nanoemulsion formulation and market formulation. Results indicated that there are
      no significant different between ketoprofen entrapped POEs nanoemulsion and
      market formulation in carrageenan-induced rat hind paw edema study and
      carrageenan-induced hyperalgesia pain threshold study. However, it shows a
      significant different between POEs nanoemulsion formulation and control group in
      these studies at p<0.05. From these results it was concluded that the developed
      nanoemulsion have great potential for topical application of ketoprofen.

PMID- 21099146
TI  - Sunlight photo-assisted TiO2-based pilot plant scale remediation of (simulated)
      contaminated aquatic sites.
AB  - A tubular-type solar photoreactor system powered by commercial solar panels and
      consisting of six 20-tube modules (Pyrex glass) to mimic a pilot plant scale
      configuration was designed and constructed to examine the remediation of
      simulated wastewaters contaminated with various classes of organic pollutants
      such as endocrine disruptors (e.g. bisphenol A), anionic surfactants (sodium
      butylnaphthalenesulfonate and sodium dodecyl- benzenesulfonate), herbicides (e.g.
      2,4-dichlorophenoxyacetic acid) and a commercial dishwasher detergent. Photo
      oxidative processes followed first-order kinetics expressed in terms of the total
      light energy (in kJ) that impinged on the photoreactor. The influence of TiO2
      loading and circulation flow rate of the wastewaters on the dynamics of the photo
      oxidation to mineralization (loss of total organic carbon, TOC, or formation of
      sulfate ions) was investigated. The optimal operational parameters were: TiO2
      loading, 2 g L-1; circulation flow rate, 7.5 L min-1. On a sunny day, near-
      quantitative mineralization of the contaminants was achieved after only 4 h of
      irradiation that corresponded to an accumulated energy of ca 1380 kJ.

PMID- 21099148
TI  - The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1.
AB  - Linopirdine is a well known blocker of voltage-gated potassium channels from the
      Kv7 (or KCNQ) family that generate the so called M current in mammalian neurons.
      Kv7 subunits are also expressed in pain-sensing neurons in dorsal root ganglia,
      in which they modulate neuronal excitability. In this study we demonstrate that
      linopirdine acts as an agonist of TRPV1 (transient receptor potential vanilloid
      type 1), another ion channel expressed in nociceptors and involved in pain
      signaling. Linopirdine induces increases in intracellular calcium concentration
      in human embryonic kidney 293 (HEK293) cells expressing TRPV1, but not TRPA1 and
      TRPM8 or in wild-type HEK293 cells. Linopirdine also activates an inward current
      in TRPV1-expressing HEK293 cells that is almost completely blocked by the
      selective TRPV1 antagonist capsazepine. At low concentrations linopirdine
      sensitizes both recombinant and native TRPV1 channels to heat, in a manner that
      is not prevented by the Kv7-channel opener flupirtine. Taken together, these
      results indicate that linopirdine exerts an excitatory action on mammalian
      nociceptors not only through inhibition of the M current but also through
      activation of the capsaicin receptor TRPV1.

PMID- 21099147
TI  - A potential role of alpha-7 nicotinic acetylcholine receptor in cardiac
      angiogenesis in a pressure-overload rat model.
AB  - This work investigated the expression of alpha-7 nicotinic acetylcholine receptor
      (alpha7nAChR) in the left ventricle and its putative role in cardiac angiogenesis
      in a pressure overload rat model induced by abdominal aorta coarctation. Blood
      pressure and protein levels of alpha7nAChR were measured at 4, 8, 12, and 16
      weeks after surgery. mRNA levels of alpha7nAChR, cardiac vagus nerve function,
      cardiac hypertrophy, and microvessel density of the left ventricle were
      determined at the final 16-week period. The role of alpha7nAChR in angiogenesis
      was evaluated. It was found that systolic blood pressure above the coarctation
      site was greater at 16 weeks after coarctation and expression of alpha7nAChR was
      significantly increased at both mRNA and protein levels in the left ventricle
      compared with the control. Positive staining for receptors was mainly focused
      around vessels and among the degenerated cardiomyocytes. Cardiac vagus nerve
      function was significantly attenuated; microvessel density was markedly increased
      and was associated with cardiac hypertrophy. Activation of alpha7nAChR induced
      tube formation of cultured human umbilical vein endothelial cells (HUVECs). We
      conclude that expression of alpha7nAChR was increased at 16 weeks after
      coarctation, and this might be a compensatory response to decreased vagus nerve
      function and cardiac hypertrophy and may also play a role in cardiac
      angiogenesis.

PMID- 21099149
TI  - Diazepam-induced increases of synaptic efficacy in the hippocampal-medial
      prefrontal cortex pathway are associated with its anxiolytic-like effect in rats.
AB  - The medial prefrontal cortex (mPFC) has recently been shown to be an important
      brain region for emotional function as well as cognitive ability. In previous
      experiments, we studied the population spike amplitude (PSA) in the mPFC induced
      by stimulation of the CA1/subicular region as an index of synaptic efficacy in
      the hippocampal-mPFC pathway. In the present study, we investigated the
      relationship between the anxiolytic effect of diazepam and the changes of
      synaptic efficacy in this pathway. In contextual fear conditioning tests,
      diazepam (0.1 mg/kg) was not effective for fear-related freezing behavior. At a
      dose of 0.5 mg/kg, diazepam decreased freezing behavior 20 min after
      administration, with no discernible effect 30 min after administration. In
      electrophysiological experiments, 0.1 mg/kg diazepam had no effect on the PSA in
      the mPFC. In contrast, 0.5 mg/kg diazepam increased the PSA in the mPFC within 30
      min of administration; however, this PSA increase was attenuated over the 30-min
      period. Based on these results, we propose that the diazepam-induced PSA increase
      in the mPFC is associated with its anxiolytic-like effect.

PMID- 21099150
TI  - Comparison of two electroretinography systems used in dogs: the HMsERG and the
      RETIport.
AB  - The purpose of the study was to compare two different electroretinography (ERG)
      instruments used on the same animal in a laboratory setting. Retinal function in
      both eyes of 12 healthy miniature schnauzers was evaluated under general
      anesthesia. Scotopic and photopic ERGs were recorded by the HMsERG and the
      RETIport using the Dog Standard Protocol recommended by the European College of
      Veterinary Ophthalmologists (ECVO). The waveforms of the ERGs obtained by the two
      ERG units were similar to those described in previous studies. The 90% reference
      ranges using the multiple of medians (MoM) showed that the changes in ERG
      parameters obtained by the HMsERG unit were very similar to those of the RETIport
      for most ERG responses, except for a few. The results demonstrate that the two
      ERG systems are comparable for evaluating retinal function in dogs. Further, the
      results also show that it is necessary to establish ERG system-specific limits of
      normality in each laboratory or clinic in order to obtain a correct diagnosis,
      for example by using a graphical representation of the 90% reference range.

PMID- 21099151
TI  - Guidelines for Radiation Safety in Interventional Cardiology (JCS 2006). Digest
      version.

PMID- 21099152
TI  - Effect of composite post placement on bonding to root canal dentin using 1-step
      self-etch dual-cure adhesive with chemical activation mode.
AB  - This study evaluated the effect of composite post placement and/or light
      irradiation of dual-cure resin composite on adhesion to root canal dentin using
      the chemical activation mode of a 1-step self-etch dual-cure adhesive. Post
      spaces were prepared in extracted premolars. Root canal spaces were applied with
      Unifil Core EM Self-Etching Bond, which was chemically-polymerized, and then
      filled with Unifil Core EM with or without the placement of composite post. Half
      the specimens of each group were light-cured for 10 seconds and the other half
      were chemically-cured in darkness for 30 minutes. After 24 h storage,
      microtensile bond strengths (uTBS) at the coronal and apical regions were
      measured. When light-curing, placement of the composite post significantly
      reduced the uTBS to root canal dentin. On the other hand, when chemical-curing,
      there was no significant difference in uTBS between with and without placement of
      the composite post.

PMID- 21099153
TI  - Wear of opposing teeth by posterior composite resins--evaluation of newly
      developed wear test methods.
AB  - In the present study, enamel wear against indirect composite resins was evaluated
      using two newly designed wear test methods: a rotating sliding wear test and a
      buff wear test. For the composite resins investigated in this study, their
      surface morphologies were examined using a scanning probe microscope after buff
      polishing. After the wear tests, enamel was worn down by hard fillers that
      protruded from the abraded resin matrices. Notably, enamel wear was induced by
      composite materials with a Vickers hardness number (VHN) greater than 45 and that
      the amount of enamel wear increased with increasing hardness of the composite
      material. Therefore, 45 VHN was the critical hardness value for composite resins
      at which antagonistic enamel wear would occur. Besides, the D-value obtained from
      the buff wear test indicated not only the relative wear resistance of the
      composite resin itself, but also its potential risk to induce antagonistic enamel
      wear.

PMID- 21099154
TI  - Effects of water-storage on the physical and ultramorphological features of
      adhesives and primer/adhesive mixtures.
AB  - The aims of this study were to evaluate the ultimate tensile strength (UTS) and
      elastic modulus (E) of adhesives, and primer/adhesive mixtures after aging for 6
      months in water or oil; and to compare silver uptake patterns under the TEM. A
      one-step self-etching adhesive (One-up Bond F: OB), two two-step self-etching
      primers (SE Bond: SE and Protect Bond: CP), and two etch-and-rinse systems
      (Single Bond: SB and Prime&Bond NT: PB) were used. Bonding and primer solutions
      of self-etching systems were also mixed (SE+P and CP+P). Most adhesives presented
      decreased UTS after water-storage. Similar or increased UTS was observed after
      oil storage. Except for SB, E values did not change after water-storage, but they
      increased after storage in oil. OB, CP+P and SE+P presented more silver uptake.
      The effects of water-storage were material-dependent, and significantly affected
      the mechanical properties and silver uptake patterns of adhesives.

PMID- 21099155
TI  - Carbon dioxide laser application enhances the effect of silane primer on the
      shear bond strength between porcelain and composite resin.
AB  - The purpose of this study was to evaluate the effect of carbon dioxide laser
      irradiation on the performance of silane coupling agent as an adhesion promoter.
      The carbon dioxide laser used in this study was Opelaser 03S II, which irradiated
      the silane coupling agent applied on the adhesive surface of porcelain. Before
      and after thermal cycling, shear bond strength was measured using a universal
      testing machine. Without primer treatment, most of the specimens failed
      adhesively before reaching the end of the thermal cycling period. For the
      specimens irradiated with carbon dioxide laser after primer treatment, their
      shear bond strengths before and after thermal cycling were higher than those
      treated with primer only -with a significantly pronounced difference between
      these two groups especially after thermal cycling. Therefore, a combined surface
      treatment which involved silane application followed by laser treatment was
      feasible and efficacious for chairside porcelain repair.

PMID- 21099157
TI  - Effect of application time of colloidal platinum nanoparticles on the
      microtensile bond strength to dentin.
AB  - The purpose of this study was to investigate the effect of application time of
      colloidal platinum nanoparticles (CPN) on bond strength. Dentin surfaces were
      subjected to one of the following treatments: (A) Etching with 10% citric acid-3%
      FeCl(3 )solution (10-3 solution); (B) Etching with 10-3 solution followed by
      applying CPN as a primer solution for 10, 20, 30, or 60 seconds; and (C) Priming
      with CPN for 10, 20, 30, or 60 seconds followed by etching with 10-3 solution. An
      acrylic rod was bonded to each treated dentin surface using 4-META/MMA-TBB resin.
      Bonded specimens were sectioned into beams for microtensile bond strength
      testing. In groups (B) and (C), highest bond strength was obtained when dentin
      surfaces were treated with CPN for 30 seconds. This meant that the CPN primer
      solution either enhanced the penetration of resin into dentin or the degree of
      conversion of 4-META/MMA-TBB resin. Within the limitations of this study,
      treatment with 0.1 mN CPN primer solution followed by 20 seconds of water rinsing
      resulted in high bond strength.

PMID- 21099156
TI  - Effectiveness of scaffolds with pre-seeded mesenchymal stem cells in bone
      regeneration--assessment of osteogenic ability of scaffolds implanted under the
      periosteum of the cranial bone of rats.
AB  - To date, there has been no study on the development of novel regimens based on
      the following tissue engineering principles: seeding and culturing mesenchymal
      stem cells (MSCs) on a scaffold before surgery or injecting cultured MSCs into a
      scaffold during surgery. The purpose of this study was to assess the in vivo
      osteogenic ability of scaffold/MSCs implanted beneath the periosteum of the
      cranial bone of rats in three different sample groups: one in which MSCs were pre
      seeded and cultured on a scaffold to produce the 3-D woven fabric scaffold/MSC
      composite using osteo-lineage induction medium, one in which cultured MSCs
      produced by osteo-lineage induction in cell cultivation flasks were injected into
      a scaffold during surgery and a control group, in which only the 3-D woven fabric
      scaffold was implanted. The results indicate that pre-seeding MSCs on a scaffold
      leads to a higher osteogenic ability than injecting cultured MSCs into a scaffold
      during surgery.

PMID- 21099158
TI  - Degree of immobilization of synthetic RGDS(PO(3)H(2))PA peptides on titanium
      surfaces.
AB  - The purpose of this study was to characterize the chemical interaction between
      titanium surfaces and the peptide RGDS(PO(3)H(2))PA (P-RGD) synthesized from RGD
      peptide (RGD) and o-phospho-L-serine (P-Ser), and to determine the degree of
      peptide immobilization on the titanium surface. X-ray photoelectron spectroscopy
      showed that the adsorption amount of RGD was significantly smaller than those of
      P-Ser and P-RGD (p<0.05). Furthermore, although it appeared that P-RGD bonded to
      the surface, ultrasonic rinsing with water caused it to dissociate, releasing RGD
      and leaving only S(PO(3)H(2))PA bonded to the surface. These findings show that
      although it remains difficult to obtain a stable P-RGD layer, the phosphate
      functional group greatly improves immobilization of the molecule on titanium
      surfaces.

PMID- 21099160
TI  - In vitro study of anti-suck-back ability by themselves on new high-speed air
      turbine handpieces.
AB  - The anti-suck-back ability of five new high-speed air turbine handpiece models
      was evaluated in this study. First, suck-back pressure with water displacement
      within a glass tube was measured. Next, under three different conditions, how
      many on-off times it takes before fluorescent stains became visible on a piece of
      gauze at the exhaust vent was counted and the presence of fluorescent stains on
      the exhaust vents itself was examined. As a result, the water height for each
      part of one handpiece, the TWINPOWER TURBINE PAR-4HX-O, was below 0 mm. Except
      for under full emersion, this model, the TWINPOWER TURBINE PAR-4HX-O, did not
      have any visible fluorescence penetration to the exhaust vent even after 500 on
      off switches under fume/mist conditions. Conversely, the other handpieces (Ti-Max
      X700L, T1 CONTROL, SYNEA TA-98CLED, GENTLE silence LUX 8000B) showed suck-back.
      In conclusion, the first mentioned new turbine handpiece, the TWINPOWER TURBINE
      PAR-4HX-O, had a possibility of no suck-back by itself. However, full immersion
      of the whole head of the handpiece which is not completely sealed must be avoided
      to prevent liquid intake.

PMID- 21099159
TI  - Ultrastructural observation of the acid-base resistant zone of all-in-one
      adhesives using three different acid-base challenges.
AB  - The aim of this study was to analyze the ultrastructure of the dentin-adhesive
      interface using two all-in-one adhesive systems (Clearfil Tri-S Bond, TB;
      Tokuyama Bond Force, BF) after different acid-base challenges. Three solutions
      were used as acidic solutions for the acid-base challenges: a demineralizing
      solution (DS), a phosphoric acid solution (PA), and a hydrochloric acid solution
      (HCl). After the acid-base challenges, the bonded interfaces were examined by
      scanning electron microscopy. Thickness of the acid-base resistant zone (ABRZ)
      created in PA and HCl was thinner than in DS for both adhesive systems. For BF
      adhesive, an eroded area was observed beneath the ABRZ after immersion in PA and
      HCl, but not in DS. Conversely for TB adhesive, the eroded area was observed only
      after immersion in PA. In conclusion, although the ABRZ was observed for both all
      in-one adhesive systems, its morphological features were influenced by the
      ingredients of both the adhesive material and acidic solution.

PMID- 21099161
TI  - Evaluation of the static frictional coefficients of Co-Cr and gold alloys for
      cone crown telescope denture retainer applications.
AB  - The static frictional coefficients (SFC) of a Co-Cr and a gold alloys were
      evaluated for the application of a cone crown telescope system in removable
      prosthesis. The SFCs of the Co-Cr alloy were lower than those of the gold alloy.
      The SFC of the gold alloy decreased by annealing at 85 degrees C in air and was
      restored by re-polishing, although that of the Co-Cr alloy was stable
      irrespective of the annealing. The XPS analysis revealed the formation of a
      surface oxide layer on the gold alloy after annealing. The decrease in the SFC of
      the gold alloy may have been caused by the formation of an oxide layer on the
      surface due to annealing. The relationships among such factors as the retentive
      force, SFC and cone crown angle indicate that the angle of the Co-Cr alloy should
      be lower than that of the gold alloy based on the Korber's model.

PMID- 21099162
TI  - Application of 4-META/MMA-TBB resin for fixation of membrane to tooth in guided
      tissue regeneration in dog.
AB  - The aim of this study was to evaluate 4-META/MMA-TBB resin as an alternative to
      sling sutures for fixation of membrane to tooth in GTR in terms of its effect on
      tissue regeneration. Dehiscence periodontal defects were created in 6 dogs which
      were divided at random into two groups, 3 dogs in each group: an experimental
      group, in which non-absorbable or absorbable membrane was fixed to the teeth with
      4-META/MMA-TBB resin; and a control group, in which sling sutures were applied to
      fix the two types of membrane. Histologic and histometric evaluation was carried
      out at 8 weeks post-operatively to determine healing response in each group. Both
      methods of achieving membrane fixation to tooth were effective in inhibiting
      epithelial migration and encouraging formation of regenerated periodontal tissues
      around the root surfaces. These results suggest that 4-META/MMA-TBB resin is as
      effective as sling sutures in achieving membrane fixation in GTR and is,
      moreover, easier to apply.

PMID- 21099163
TI  - Effect of overglazed and polished surface finishes on the compressive fracture
      strength of machinable ceramic materials.
AB  - Controversy prevails over the effect of overglazing on the fracture strength of
      ceramic materials. Therefore, the effects of different surface finishes on the
      compressive fracture strength of machinable ceramic materials were investigated
      in this study. Plates prepared from four commercial brands of ceramic materials
      were either surface-polished or overglazed (n=10 per ceramic material for each
      surface finish), and bonded to flat surfaces of human dentin using a resin
      cement. Loads at failure were determined and statistically analyzed using two-way
      ANOVA and Bonferroni test. Although no statistical differences in load value were
      detected between polished and overglazed groups (p>0.05), the fracture load of
      Vita Mark II was significantly lower than those of ProCAD and IPS Empress CAD,
      whereas that of IPS e.max CAD was significantly higher than the latter two
      ceramic materials (p<0.05). It was concluded that overglazed and polished
      surfaces produced similar compressive fracture strengths irrespective of the
      machinable ceramic material tested, and that fracture strength was material
      dependent.

PMID- 21099164
TI  - Effect of beta tricalcium phosphate particle size on recombinant human platelet
      derived growth factor-BB-induced regeneration of periodontal tissue in dog.
AB  - The aim of this study was to investigate the effect of beta tricalcium phosphate
      (beta-TCP) particle size on recombinant human platelet-derived growth factor-BB
      (rhPDGF-BB)-induced regeneration of periodontal tissue in dog. The control group
      (rhPDGF-BB alone) was characterized by incomplete, newly formed bone. The large
      particle beta-TCP (L-TCP(O))/rhPDGF-BB group showed a statistically significant
      increase in both new bone and cementum formation compared to the small-particle
      beta-TCP (S-TCP(G))/rhPDGF-BB group. These findings suggest that L-TCP(O)
      particle promotes rhPDGF-BB-induced formation of bone and cementum.

PMID- 21099165
TI  - Effect of the concentrations of calcium chloride and synthetic peptides in
      primers on dentin bond strength of an experimental adhesive system.
AB  - The purpose of this study was to evaluate the microtensile bond strength (MTBS)
      of an experimental adhesive system, which was prepared using different
      concentrations of calcium chloride (CaCl(2)) and synthetic peptides (pA/pB).
      Specimens were divided into six experimental groups and two control groups. In
      the experimental groups, self-etching primers used in the adhesive system
      comprised both Primer-I (Clearfil SE Bond Primer (SEP) containing 1, 5, or 10 wt%
      CaCl(2)) and Primer-II (SEP containing 0.1, 1, 5, or 10 wt% pA/pB). The negative
      control group used Primer-I containing 10 wt% CaCl(2 )and Primer-II containing 10
      wt% pA/pB. The positive control group used Clearfil SE Bond only. Respective
      primers, bonding resin, and composite paste were applied and photopolymerized
      individually on flattened dentin surfaces of extracted human molars. All
      specimens were subjected to MTBS testing (n=20). Two-way ANOVA revealed
      significant differences in MTBS among CaCl(2 )concentrations in Primer-I and
      pA/pB concentrations in Primer-II (p<0.001), and there was a significant
      interaction between these two factors (p=0.011).

PMID- 21099166
TI  - Geometric design method for class I inlay cavity.
AB  - The purpose of the present study was to establish a geometric design method for
      class I inlay cavities as a future method of computer-aided tooth preparation.
      Major occlusal fissures were used as a starting point of the cavity design and
      marked as multiple continuous line segments. An experimental cavity outline was
      defined by circular arcs and Bezier curves with three design parameters: minimum
      radius of curvature of the convex portion, taper angle of the convex portion of a
      cavity, and dovetail convexity angle. The experimental software was used to
      design class I inlay cavities for mandibular and maxillary right, first and
      second molars. Once the segments and the parameters were set, the outline was
      instantaneously drawn by the software. All design parameters worked as intended.
      Smooth class I inlay cavity outlines for molars with tool accessibility
      throughout the cavities could be obtained using the present design method.

PMID- 21099167
TI  - Mitochondrial haplogroups A and M7a confer a genetic risk for coronary
      atherosclerosis in the Japanese elderly: an autopsy study of 1,536 patients.
AB  - AIM: We previously reported significant associations between mitochondrial single
      nucleotide polymorphisms (mtSNPs) and myocardial infarction, atherothrombotic
      cerebral infarction, metabolic syndrome and type 2 diabetes. Here, we assessed
      the hypothesis that mtSNPs may confer a risk for atherosclerosis, the most
      important intermediate phenotype of ischemic cardiovascular events. METHODS: The
      subjects were 1,536 consecutive autopsy cases (827 men and 709 women). The
      average age at death was 80 years. The severity of coronary atherosclerosis was
      semi-quantitatively examined on cut sections. We examined 149 mtSNPs using the
      PCR-Luminex method, with a success rate of 97%. Phylogenetic tree analysis
      yielded 36 haplogroups. Multiple logistic regression analysis was performed after
      adjustments for sex, age, and conventional cardiovascular risk factors. RESULTS:
      Among the 45 mtSNPs with minor genotype frequencies >0.05, 6 mtSNPs were
      associated with coronary atherosclerosis. Among 10 haplogroups with frequencies
      >0.04, haplogroups A and M7a were significantly associated with coronary
      atherosclerosis, with odds ratios (95% confidence intervals) of 1.80 (1.09-2.97;
      p=0.023) and 1.92 (1.23-3.01; p=0.004), respectively. Haplogroup D4a, which was
      previously reported to be associated with extreme longevity in a Japanese
      population, was associated with pathological myocardial infarction in men with an
      odds ratio of 2.05 (1.01-4.14; p=0.046). CONCLUSIONS: The mitochondrial
      haplogroups A and M7a confer a significant risk for coronary atherosclerosis in
      the Japanese. The mitochondrial haplogroup may contribute some genetic risk for
      coronary heart disease.

PMID- 21099168
TI  - Age is a major pathobiological determinant of aortic dilatation: a large autopsy
      study of community deaths.
AB  - AIM: Aortic dilatation is a well-known phenomenon in the elderly. We therefore
      aimed to study the pathobiological determinants of aortic dilatation. METHODS:
      Retrospective chart review. The subjects were 833 consecutive autopsy cases (616
      men and 217 women) of community deaths. The age at death ranged from 20 to 94
      years, with an average of 59.2 years. We measured the internal circumference of
      the aortic root, arch, descending portion, abdominal portion, and bifurcation in
      unfixed opened aorta at the time of autopsy. RESULTS: The simple correlation
      between age and aortic circumference was strongest for the descending portion,
      followed by the arch, abdominal portion, root, and bifurcation. The simple
      correlation coefficient reached 0.836 for the descending portion (p < 0.001). The
      circumference of the descending portion increased significantly as the severity
      of aortic atherosclerosis increased (p for trend < 0.001). Multiple regression
      analysis showed that age, sex, and body height were significantly correlated with
      the aortic circumference at all five measurement sites, while severe
      atherosclerosis was correlated with the aortic circumference at the root, and
      descending and abdominal portions. Six contributing factors (age, sex, body
      height, smoking history, hypertension, and severe atherosclerosis) explained
      68.5% of the variance in circumference in the descending portion; age explained
      57.5%; sex 8.4%; body height 1%; and severe atherosclerosis 0.8%. CONCLUSION: The
      contribution of atherosclerosis to aortic dilation was very weak, representing
      less than one seventieth of the contribution of age. The aortic circumference,
      especially in the descending portion, serves as an excellent age-related marker.

PMID- 21099170
TI  - [Preface for special issue on radiological technology research involving observer
      performance study].

PMID- 21099169
TI  - Loss of clusterin limits atherosclerosis in apolipoprotein E-deficient mice via
      reduced expression of Egr-1 and TNF-alpha.
AB  - AIM: Whether clusterin/apolipoprotein J is antiatherogenic or proatherogenic is
      controversial. We reported that clusterin was markedly induced in media and
      neointima after vascular injury and that reduced clusterin expression reduced the
      proliferation of vascular smooth muscle cells (VSMCs), which induced G1 arrest
      via p53 and p21. The purpose of this study was to investigate the physiological
      function of clusterin in atherosclerosis using double-knockout mice (D-KO) of
      apolipoprotein E-deficient mice (apoE-KO) and clusterin-deficient mice (CLU-KO).
      METHODS AND RESULTS: Atherosclerotic lesions in the aortic root were quantitated
      at 20 weeks of age. Atherosclerotic lesions of D-KO were significantly smaller
      than those of apoE-KO (D-KO: 0.176+/-0.078 mm(2) vs. apoE-KO: 0.365+/-0.164
      mm(2), p< 0.001). To identify underlying atherosclerotic mechanisms that were
      blocked by loss of clusterin, we performed immunohistochemical analysis of Egr-1.
      Egr-1 immunoreactivity in the nuclei of VSMCs in atherosclerotic lesions of apoE
      KO was upregulated, whereas it was not in D-KO lesions. Western blotting
      demonstrated that the expression levels of Egr-1 and TNF-alpha in the D-KO were
      significantly lower than those in the apoE-KO. When VSMCs and macrophages were
      obtained from D-KO and apoE-KO, Western blotting showed that the expression
      levels of Egr-1 and TNF-alpha in VSMCs and macrophages of D-KO were significantly
      lower than those of apoE-KO. CONCLUSION: Loss of clusterin strongly suppressed
      apoE-KO-induced atherosclerotic lesions at a step prior to the expression of Egr
      1 and TNF-alpha, suggesting that clusterin is a candidate for an antiatherogenic
      target.

PMID- 21099171
TI  - [Objective evaluation of visual fatigue for reading of radiographs displayed on
      medical-grade liquid-crystal displays].
AB  - The aim of this study was to evaluate visual fatigue objectively by measuring
      accommodation time and critical fusion frequency (CFF) before and after reading
      posteroanterior chest radiographs displayed on medical-grade liquid-crystal
      displays (LCDs) under different monitor conditions. A color LCD (500, 170 cd/m2)
      and a monochrome LCD (500 cd/m2) were used in this study. Six observers
      independently kept reading the radiographs for two hours to understand various
      lung nodules in the "Fatigue Session". Objective visual fatigue was measured by
      using the accommodation device and the CFF meter before and after the Fatigue
      Session. The ambient lighting of the laboratory was set at 35 lux. Both the
      accommodation time and the CFF between before and after the Fatigue Session
      indicated statistically significant differences (p<0.05). Our results on
      accommodation time and CFF before and after reading the radiographs on medical
      grade LCDs indicated that visual fatigue could be evaluated objectively.

PMID- 21099172
TI  - [Evaluation of image quality using the normalized-rank approach for primary class
      liquid-crystal display (LCD) monitors with different colors and resolution].
AB  - The purposes of this study were to evaluate the image quality of five types of
      liquid-crystal display (LCD) monitors by utilizing the normalized-rank approach
      and to investigate the effect of LCD monitor specifications, such as display
      colors, luminance, and resolution, on the evaluators' ranking. The LCD monitors
      used in this study were 2, 3 and 5 mega-pixel monochrome LCD monitors, and 2 and
      3 mega-pixel color LCD monitors (Eizo Nanao Corporation). All LCD monitors were
      calibrated to the grayscale standard display function (GSDF) with different
      maximum luminance (recommended luminance) settings. Also, four kinds of
      radiographs were used for observer study based on the normalized-rank approach:
      three adult chest radiographs, three pediatric chest radiographs, three ankle
      joint radiographs, and four double-contrasted upper gastrointestinal radiographs.
      Ten radiological technologists participated in the observer study. Monochrome LCD
      monitors exhibited superior ranking with statistically significant differences
      (p<0.05) compared to color LCD monitors in all kinds of radiographs. The major
      difference between monochrome and color monitors was luminance. Therefore, it is
      considered that the luminance of LCD monitors affects observers' evaluations
      based on image quality. Moreover, in the case of radiographs that include high
      frequency image components, the monitor resolution also affects the evaluation.
      In clinical practice, it is necessary to optimize the luminance and choose
      appropriate LCD monitors for diagnostic images.

PMID- 21099173
TI  - [An investigation of the subjective assessment of fluoroscopic imaging using
      instantaneous detectability].
AB  - Instantaneous detectability was introduced in a method for the subjective
      assessment of fluoroscopic images, particularly in the interventional radiology
      (IVR) procedure. Quantitatively, instantaneous detectability was obtained by
      measuring the time required for observers to detect the tip of a linear pattern,
      such as a guide wire, just after the image is displayed. Dynamic images used in
      this measurement, which mimic degraded fluoroscopic images, were created in the
      computer simulation software by adding a low-contrast linear pattern to a noisy
      background image. Radiological technologists and students in the faculty of
      computer engineering participated in the assessment, and all measurements were
      performed using a personal computer system. Even if the contrast-to-noise ratio
      was identical, instantaneous detectability was remarkably increased when the
      background noise was dominated by higher frequency components. Also, the sign
      test suggested that a frame rate of 30 f/s significantly improved detectability
      compared to a frame rate of 15 f/s. These results enable us to discuss new
      possibilities for image processing and the optimization of system performance.
      Although the standard deviation of the measured inter- and intra-observer data
      was large, statistical significance should be suitably examined by a paired
      comparison like the sign test, which will be one of the important analyzers in
      experiments investigating human performance.

PMID- 21099174
TI  - [Comparison of noise characteristics of direct and indirect conversion flat panel
      detectors].
AB  - Flat-panel detector (FPD) digital radiography systems have direct and indirect
      conversion systems, and the 2 conversion systems provide different imaging
      performances. We measured some imaging performances [input-output characteristic,
      presampled modulation transfer function (presampled MTF), noise power spectrum
      (NPS)] of direct and indirect FPD systems. Moreover, some image samples of the
      NPSs were visually evaluated by the pair comparison method. As a result, the
      presampled MTF of the direct FPD system was substantially higher than that of the
      indirect FPD system. The NPS of the direct FPD system had a high value for all
      spatial frequencies. In contrast, the NPS of the indirect FPD system had a lower
      value as the frequency became higher. The results of visual evaluations showed
      the same tendency as that found for NPSs. We elucidated the cause of the
      difference in NPSs in a simulation study, and we determined that the cause of the
      difference in the noise components of the direct and indirect FPD systems was
      closely related to the presampled MTF.

PMID- 21099175
TI  - [Relationship between image quality and signal detectability in CR and FPD
      systems].
AB  - With the screen/film X-rays imaging system, Wakamatsu et al. reported that there
      was a close relationship between the square root of spectral signal-to-noise
      ratio area and sensitivity measure d' in receiver operating characteristic (ROC)
      analysis. In this study, we investigated the relationship between image quality
      and signal detectability in two digital X-ray imaging systems using computed
      radiography (CR) and a flat panel detector (FPD). We used urethane resin balls
      with a diameter of 2 mm as a signal for cases samples in ROC analysis. In this
      experiment, the square root of the spectral signal-to-noise ratio area was
      closely related to d' in ROC analysis in both digital X-ray imaging systems. In
      addition, when the exposure dose increased, signal detectability improved, but
      then saturated at one level. These results suggest that the exposure dose can be
      reduced when the optimal dose setting can be determined.

PMID- 21099176
TI  - [Correlation between basic imaging properties and subjective evaluations of two
      digital radiographic X-ray systems based on direct-conversion flat panel
      detector].
AB  - The purpose of this study was to examine the correlation between the basic
      imaging properties of two digital radiographic X-ray systems with a direct
      conversion flat-panel detector and their image qualities, which were evaluated by
      the observer in hard copy and soft copy studies. The subjective image quality was
      evaluated and compared in terms of the low-contrast detectability and image
      sharpness in the two digital radiographic X-ray systems. We applied the
      radiographs of a contrast detail phantom to the evaluation of low-contrast
      detectability and analyzed the contrast detail diagrams. Finally, low-contrast
      detectability was evaluated by the image quality figure (IQF) calculated from the
      contrast detail diagrams. Also, the subjective image sharpness of human dry bones
      of two systems was examined and evaluated by the normalized-rank method. The
      results indicated that System A tended to provide superior subjective image
      quality compared to System B in both observer studies. We also found high
      correlations between IQFs and basic imaging properties, such as the noise power
      spectrum (NPS) and the noise equivalent quantum (NEQ). In conclusion, the low
      contrast detectability of the two digital radiographic X-ray systems with a
      direct conversion flat-panel detector corresponded to the NPS and the NEQ in both
      outputs (soft copy and hard copy). On the other hand, the subjective image
      sharpness of human dry bones was affected by their noise properties.

PMID- 21099177
TI  - [Effect of signal selection in receiver operating characteristics (ROC)
      analysis].
AB  - Selection of the signal is one of the major factors in a receiver operating
      characteristic (ROC) study for evaluating the diagnostic accuracy of medical
      imaging systems. We investigated the effect of signal selections in ROC studies
      which were applied to evaluate a difference between the two systems. Each of 50
      positive and 50 negative images obtained with and without two different types of
      phantom signals, but with the same background noise and two different digital
      imaging systems, were used as case samples. We assumed that two different types
      of phantom signal could be related to image resolution and graininess,
      respectively. We employed two systems which were assumed to have advantages in
      resolution and graininess, respectively. Twelve observers participated in this
      ROC study, which aimed to compare two parameter settings in computed radiography
      systems. A statistical significance test considering case and reader variations
      was conducted for each of the ROC data sets with two different signals. As
      results, p values obtained in the statistical significance test were varied by
      changing the type of signal even if the same observer group participated and the
      same two different systems were compared (p value = 0.0003 and 0.0944). In
      conclusion, it was suggested that the selection of phantom signal for an ROC
      study could lead to different conclusions if the type of phantom signal was not
      matched to the purpose of the ROC study.

PMID- 21099178
TI  - [An experimental study of the optimal flip angle for hepatocellular magnetic
      resonance imaging with Gd-EOB-DTPA].
AB  - Gadoxetate Sodium (Gd-EOB-DTPA) is a relatively new contrast agent used for liver
      examination by magnetic resonance (MR) imaging. The setting of the flip angle
      (FA) is very important to obtain images with high contrast in hepatocellular MR
      imaging. The aim of this study was to determine the optimal FA for hepatocellular
      MR imaging. Optimal FA was estimated using a visual evaluation by observers. We
      made the visual evaluation with a paired comparison test. When the overall
      characteristic showed a significant difference, we then evaluated the optimal FA
      using a yardstick analysis. The visual evaluation by observers indicated that the
      FA was best at 22 degrees for the overall characteristic, the contrast
      characteristic, and the sharpness characteristic, and for the noise
      characteristic, the best FA was 18 degrees. All characteristics showed a
      significant difference between 18 and 22 degrees. Based on our results, the most
      important factor was the contrast characteristic for the visual evaluation, and
      we concluded that the optimal FA in hepatocelluar MR imaging was 22 degrees.

PMID- 21099180
TI  - [A robust statistic AC1 for assessing inter-observer agreement in reliability
      studies].
AB  - Understanding inter-observer variability in clinical diagnosis is crucial for
      reliability studies. As the statistical measurements of reliability, the kappa
      statistic and its extensions have been widely adopted in medical research, but it
      has been discussed that kappa is vulnerable to prevalence and presence of bias.
      As an alternative robust statistic, AC1 has attracted recent statistical
      attentions. This article describes fundamental ideas and quantitative features of
      AC1. The reliability of infrared thermoscanner as an application in detecting
      febrile patients of pandemic influenza is discussed by means of Monte Carlo
      simulation. AC1 adjusts chance agreement more appropriately than kappa and is
      regarded as a more useful measurement for assessing inter-observer agreement,
      especially when prevalence is small.

PMID- 21099179
TI  - [Experimental study of detectability of simulated lung nodule on computed
      radiography system using various X-ray beam qualities].
AB  - The purpose of this study was to discuss the optimal X-ray beam quality for
      detection of simulated lung nodule on a computed radiography system. We set up
      four types of X-ray beam quality (90 kV, 120 kV, 150 kV, and 120 kV + gadolinium
      filter), and kept the incident dose on the patient at 0.3 mGy. A receiver
      operating characteristic (ROC) analysis and a granularity measurement were used
      to evaluate the relationship between the detection of a low-contrast object and X
      ray beam quality. As a result, the areas under the ROC curve (AUC) of 90 kV and
      120 kV + gadolinium filter were significantly superior to those of 120 kV and 150
      kV (p<0.05). However, a significant difference was not observed between 90 kV and
      120 kV + gadolinium filter, 120 kV and 150 kV. The order of the granularity
      values gave good agreement with the results of visual evaluation. In conclusion,
      we considered that the optimal X-ray beam quality was 90 kV or 120 kV +
      gadolinium filter.

PMID- 21099181
TI  - [Variances among readers analyzed using the Jackknife method in ROC analysis].
AB  - To improve the reliability of statistically significant test results between two
      imaging systems in receiver operating characteristic (ROC) analysis, it was
      important to evaluate the variances among readers. In this study, we tested
      statistically significant differences with actual experimental data from ROC
      studies that were performed to evaluate the detectability of 4 kinds of image
      intensifier fluorographic films. The DBM MRMC--i.e., the software for analyze of
      statistically significant differences by the Jackknife method--was used. The
      relationship between p values obtained from analysis that treated only readers as
      a random sample in DBM MRMC, and the variances among readers, were investigated.
      The testing results showed that, when there were slight differences in the mean
      area under the corve (AUC) between imaging systems, variances among readers were
      estimated by p values, because p values indicated the degree of variance among
      readers. Furthermore, we found that p values obtained from analysis that treated
      only readers as a random sample in DBM MRMC were equal to p values of the two
      tailed paired t-test. It was considered that variances among readers could be
      analyzed by investigating the relationship between the differences in the mean
      AUC of two imaging systems and the p values obtained in a two-tailed paired t
      test.

PMID- 21099182
TI  - [Quantitative evaluation of observer performance studies: importance and
      usefulness of psychophysical experiments].

PMID- 21099183
TI  - [The theory of statistics-based sensory evaluation and its application to
      radiological technology -focusing on the Scheffe's method of paired comparison-].

PMID- 21099184
TI  - [Fundamental theory of ROC analysis and practice using DBM MRMC].

PMID- 21099187
TI  - Cynomolgus macaque CYP4 isoforms are functional, metabolizing arachidonic acid.
AB  - Cytochrome P450 (CYP) is important for metabolism of not only xenobiotics such as
      drugs, but also endogenous compounds including arachidonic acids. CYP4A11,
      CYP4F3v2, CYP4F11, and CYP4F45 have been identified in cynomolgus macaque, an
      animal species widely used for investigation of drug metabolism due to its
      evolutionary closeness to human. However, their metabolic functions have not been
      investigated. In this study, proteins were heterologously expressed in
      Escherichia coli and characterized by metabolic assays using arachidonic acids as
      substrates that are metabolized by CYP4 isoforms in human. The results showed
      that all four CYPs metabolized arachidonic acids. Therefore, cynomolgus macaque
      CYP4A11, CYP4F3v2, CYP4F11, and CYP4F45 are functional enzymes.

PMID- 21099188
TI  - Antibody responses induced by Japanese whole inactivated vaccines against equine
      influenza virus (H3N8) belonging to Florida sublineage clade2.
AB  - In 2010, the World Organisation for Animal Health recommended the inclusion of a
      Florida sublineage clade2 strain of equine influenza virus (H3N8), which is
      represented by A/equine/Richmond/1/07 (Richmond07), in equine influenza vaccines.
      Here, we evaluate the antigenic differences between Japanese vaccine strains and
      Richmond07 by performing hemagglutination inhibition (HI) assays. Ferret
      antiserum raised to A/equine/La Plata/93 (La Plata93), which is a Japanese
      vaccine strain, reacted with Richmond07 at a similar titer to La Plata93.
      Moreover, two hundred racehorses exhibited similar geometric mean HI antibody
      titers against La Plata93 and Richmond07 (73.1 and 80.8, respectively).
      Therefore, we can expect the antibody induced by the current Japanese vaccines to
      provide some protection against Richmond07-like viruses.

PMID- 21099189
TI  - Genetically diverse group C rotaviruses cause sporadic infection in Korean
      calves.
AB  - This study examined the prevalence and genetic diversity of the bovine group C
      rotaviruses (GCRVs) in a total of 127 diarrhea fecal samples of calves from 52
      Korean native beef calf herds using RT-PCR and nested PCR. Overall, seven of the
      127 fecal samples (5.5%) from seven of the 52 herds (13.5%) tested positive for
      bovine GCRVs only by nested PCR. Sequence and phylogenetic analyses of a partial
      VP6 gene showed that Korean bovine GCRVs had marked genetic diversity; two Korean
      strains belonged to the bovine lineage, whereas five Korean strains belonged to
      the porcine lineage. These results suggest that the genetically diverse bovine
      GCRVs cause sporadic infections in diarrheic calves in South Korea.

PMID- 21099190
TI  - 'Do not attempt resuscitation' and 'cardiopulmonary resuscitation' in an
      inpatient setting: factors influencing physicians' decisions in Switzerland.
AB  - OBJECTIVE: To determine the prevalence of cardiopulmonary resuscitation (CPR) and
      do-not-attempt-resuscitation (DNAR) orders, to define factors associated with
      CPR/DNAR orders and to explore how physicians make and document these decisions.
      METHODS: We prospectively reviewed CPR/DNAR forms of 1,446 patients admitted to
      the General Internal Medicine Department of the Geneva University Hospitals, a
      tertiary-care teaching hospital in Switzerland. We additionally administered a
      face-to-face survey to residents in charge of 206 patients including DNAR and CPR
      orders, with or without patient inclusion. RESULTS: 21.2% of the patients had a
      DNAR order, 61.7% a CPR order and 17.1% had neither. The two main factors
      associated with DNAR orders were a worse prognosis and/or a worse quality of
      life. Others factors were an older age, cancer and psychiatric diagnoses, and the
      absence of decision-making capacity. Residents gave four major justifications for
      DNAR orders: important comorbid conditions (34%), the patients' or their family's
      resuscitation preferences (18%), the patients' age (14.2%), and the absence of
      decision-making capacity (8%). Residents who wrote DNAR orders were more
      experienced. In many of the DNAR or CPR forms (19.8 and 16%, respectively), the
      order was written using a variety of formulations. For 24% of the residents, the
      distinction between the resuscitation order and the care objective was not clear.
      38% of the residents found the resuscitation form useful. CONCLUSION: Patients'
      prognosis and quality of life were the two main independent factors associated
      with CPR/DNAR orders. However, in the majority of cases, residents evaluated
      prognosis only intuitively, and quality of life without involving the patients.
      The distinction between CPR/DNAR orders and the care objectives was not always
      clear. Specific training regarding CPR/DNAR orders is necessary to improve the
      CPR/DNAR decision process used by physicians.

PMID- 21099191
TI  - Percutaneous absorption of pimecrolimus is not increased in patients with
      moderate to severe atopic dermatitis when pimecrolimus cream 1% is applied under
      occlusion.
AB  - AIM: To evaluate the systemic exposure of pimecrolimus cream 1% applied under
      occlusion in atopic dermatitis (AD) patients. METHODS: A noncomparative, open
      label study conducted in 3 groups of moderate to severe AD patients: A (adults, n
      = 9), B (adolescents, n = 4) and C (children, n = 6). Pimecrolimus cream 1% was
      applied twice daily for 8.5 days with overnight occlusion in patients with
      investigator's global assessment scores of >=3 and AD involving at least 30% of
      their body surface area. Pimecrolimus blood concentrations were analyzed.
      RESULTS: The highest pimecrolimus blood concentrations observed in adults,
      adolescents and children were 1.84, 0.55 and 1.29 ng/ml, respectively.
      Pimecrolimus blood concentrations and affected body surface area showed no
      apparent correlation. CONCLUSION: No measurable differences were found in
      pimecrolimus blood concentrations, efficacy and safety profile when pimecrolimus
      cream 1% was applied under occlusion versus application without occlusion. These
      findings reflect the high lipophilic properties of pimecrolimus.

PMID- 21099192
TI  - Role of short-term antibiotic therapy at the moment of catheter removal after
      laparoscopic radical prostatectomy.
AB  - OBJECTIVE: To assess the role of short-term antibiotic therapy (ABT) in
      preventing urinary tract infection (UTI) after catheter removal following
      laparoscopic radical prostatectomy (LRP). METHODS: 729 consecutive patients
      underwent LRP by one of two surgeons. One surgeon systematically prescribed a 3
      day course of ABT (ciprofloxacin) starting the day before catheter removal; the
      other surgeon did not. The groups were compared for the incidence of symptomatic
      UTI occurring within 6 weeks after catheter removal. RESULTS: ABT was given to
      261 of 713 patients (37%), while the remaining 452 patients (63%) did not receive
      ABT. After catheter removal, UTI was observed less frequently among patients
      receiving ABT: 3.1 vs. 7.3% in those not receiving ABT (p = 0.019). A number
      needed to treat to prevent 1 UTI is 24. Hospital readmission for febrile UTI was
      observed only in patients who did not receive ABT (n = 5, 1.1 vs. 0%, p = 0.16).
      One would need to prescribe ABT for 91 LRP patients to prevent 1 case of febrile
      UTI. CONCLUSIONS: ABT at the time of catheter removal reduced the risk of
      postoperative UTI after LRP. One would need to prescribe ABT to 24 patients to
      prevent 1 case of UTI.

PMID- 21099193
TI  - Underestimated risk of bleeding after male transobturator sling procedure caused
      by early re-uptake of anticoagulation.
AB  - The management of postoperative male stress urinary incontinence (SUI) is
      changing rapidly as greater emphasis on minimizing invasiveness and reducing
      complications leads to technical innovations. Various studies have reported
      comparable continence but lower complication rates for male urethral slings than
      those observed with artificial urinary sphincters. For this reason, the
      transobturator sling procedure has been considered a safe and effective treatment
      option in male SUI patients. In this case study we report severe bleeding with a
      large hematoma that required transfusion after implantation of an AdVance(r) male
      transobturator polypropylene sling in an early re-anticoagulated patient.

PMID- 21099194
TI  - Multiple basal cell carcinomas after long-term exposure to hydrazine: case report
      and review of the literature.
AB  - Hydrazine (N(2)H(4)) is a clear, inorganic colourless liquid. It is known to be a
      skin sensitizer, a corrosive agent and it causes dermatitis on contact. Hydrazine
      is employed in chemical plants, used as a corrosion inhibitor for feed waters and
      may be added to rocket fuels. The authors report the case of a 68-year-old man
      with multiple basal cell carcinomas (BCCs) covering his arms and face. The
      patient worked in a steam power plant with extensive exposure to hydrazine for a
      period of over 10 years. The present case report strongly suggests that there may
      be a correlation between the long-term exposure to hydrazine and an increased
      risk for multiple BCCs.

PMID- 21099195
TI  - Alopecic and aseptic nodules of the scalp (pseudocyst of the scalp): a
      prospective clinicopathological study of 15 cases.
AB  - BACKGROUND: Alopecic and aseptic nodules of the scalp (AANS) is a new entity
      reported first in Japan as 'pseudocyst of the scalp'. Only retrospective studies
      have been published. OBJECTIVES: To describe the clinicopathological features of
      AANS (pseudocyst), to evaluate the response to doxycycline and to compare the
      results to those obtained from patients with dissecting cellulitis of the scalp
      (DCS). METHODS: Fifteen patients with AANS and 7 with DCS were prospectively
      included. A puncture and a biopsy were made. Patients were treated with
      doxycycline (100 mg/day) for 3 months. RESULTS: AANS affects predominantly young
      (mean age 29.7 years), Caucasian (11/15), male (14/15) patients. The main
      location of the nodules was the occiput. The associated alopecia was nonscarring.
      Material from the puncture was aseptic. The histopathology showed a deep
      granuloma in 7 of 14 patients and a nonspecific inflammation in 7 patients. After
      3 months, 8 patients were cured and 3 had a good response. CONCLUSIONS: The
      singular aspect of the nodules, the nonscarring alopecia, the deep inflammatory
      infiltrate and the efficacy of doxycycline confer specificity to AANS.

PMID- 21099196
TI  - Alezzandrini syndrome: report of a sixth clinical case.
AB  - The aim of this article is to describe an additional clinical case of a patient
      with Alezzandrini syndrome. Clinically the patient presented with unilateral
      vitiligo on the left cheek, with partial loss of hearing and vision on the same
      side.

PMID- 21099197
TI  - Characterization of the dopamine system in the brain of the tungara frog,
      Physalaemus pustulosus.
AB  - Dopamine is an evolutionarily ancient neurotransmitter that plays an essential
      role in mediating behavior. In vertebrates, dopamine is central to the mesolimbic
      reward system, a neural network concerned with the valuation of stimulus
      salience, and to the nigrostriatal motor system and hypothalamic nuclei involved
      in the regulation of locomotion and social behavior. In amphibians, dopaminergic
      neurons have been mapped out in several species, yet the distribution of
      dopaminoreceptive cells is unknown. The tungara frog, Physalaemus pustulosus, is
      an excellent model system for the study of neural mechanisms by which valuations
      of stimuli salience and social decisions are made, especially in the context of
      mate choice. In order to better understand where dopamine acts to regulate social
      decisions in this species, we have determined the distribution of putative
      dopaminergic cells (using tyrosine hydroxylase immunohistochemistry) and cells
      receptive to dopaminergic signaling (using DARPP-32 immunohistochemistry)
      throughout the brain of P. pustulosus. The distribution of dopaminergic cells was
      comparable to other anurans. DARPP-32 immunoreactivity was identified in key
      brain regions known to modulate social behavior in other vertebrates including
      the proposed anuran homologues of the mammalian amygdalar complex, nucleus
      accumbens, hippocampus, striatum, preoptic area, anterior hypothalamus,
      ventromedial hypothalamus, and ventral tegmental area/substantia nigra pars
      compacta. Due to its widespread distribution, DARPP-32 likely also plays many
      roles in non-limbic brain regions that mediate non-social information processing.
      These results significantly extend our understanding of the distribution of the
      dopaminergic system in the anuran brain and beyond.

PMID- 21099198
TI  - Ethyl chloride as an antipruritic agent: a double-blind placebo-controlled
      prospective study.
AB  - BACKGROUND: Ethyl chloride (EC) is usually used as a topical anesthetic spray
      agent. However, its antipruritic effects have never been studied, to the best of
      our knowledge. METHODS: A double-blind placebo-controlled prospective study.
      Overall, 51 healthy volunteers underwent a histamine skin prick test on both arms
      in order to trigger local pruritus. Thereafter, the affected areas were treated
      with an EC spray on one arm and a saline spray (placebo) on the other. Subjects
      as well as researchers were blind to which sprays were used. Subjects reported
      improvement in pruritus following EC/placebo and rated the intensity of pruritus
      by using a validated questionnaire and a visual analog scale. The flare and wheal
      reactions were measured in both arms before and following treatment with
      EC/placebo. RESULTS: Significant improvement in pruritus was reported more
      frequently following treatment with EC compared with placebo (84 vs. 16%; p <
      0.0001). Significant reduction in pruritus intensity was reported immediately and
      15 min following treatment with EC compared with placebo (p < 0.05). There was no
      significant difference between EC and placebo in terms of the flare and wheal
      reactions. CONCLUSIONS: EC is an effective antipruritic agent, and it does not
      change the wheal and flare reactions, making it ideal for treating pruritus
      secondary to allergy skin tests without masking their results.

PMID- 21099199
TI  - Activation of pulmonary dendritic cells and Th2-type inflammatory responses on
      instillation of engineered, environmental diesel emission source or ambient air
      pollutant particles in vivo.
AB  - The biological effects of acute particulate air pollution exposure in host innate
      immunity remain obscure and have relied largely on in vitro models. We
      hypothesized that single acute exposure to ambient or engineered particulate
      matter (PM) in the absence of other secondary stimuli would activate lung
      dendritic cells (DC) in vivo and provide information on the early immunological
      events of PM exposure and DC activation in a mouse model naive to prior PM
      exposure. Activation of purified lung DC was studied following oropharyngeal
      instillation of ambient particulate matter (APM). We compared the effects of APM
      exposure with that of diesel-enriched PM (DEP), carbon black particles (CBP) and
      silver nanoparticles (AgP). We found that PM species induced variable cellular
      infiltration in the lungs and only APM exposure induced eosinophilic
      infiltration. Both APM and DEP activated pulmonary DC and promoted a Th2-type
      cytokine response from naive CD4+ T cells ex vivo. Cultures of primary
      peribronchial lymph node cells from mice exposed to APM and DEP also displayed a
      Th2-type immune response ex vivo. We conclude that exposure of the lower airway
      to various PM species induces differential immunological responses and
      immunomodulation of DC subsets. Environmental APM and DEP activated DC in vivo
      and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered
      lung tissue barrier integrity but failed to stimulate CD4+ T cells as
      effectively. Our work suggests that respirable pollutants activate the innate
      immune response with enhanced DC activation, pulmonary inflammation and Th2
      immune responsiveness.

PMID- 21099200
TI  - Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis
      associated skin neoplasms.
AB  - BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is
      characterized by susceptibility to infection with specific human papillomavirus
      (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV)
      has been found in different epithelial skin neoplasias. OBJECTIVE: To examine
      whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV
      specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient
      with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in
      carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In
      4 of these patients, the MCPyV-positive skin lesions were from different anatomic
      locations. In addition, 1 immunosuppressed patient suffering from acquired EV
      harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested
      negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of
      30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV
      DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with
      MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV.
      Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the
      development of EV-associated skin neoplasms.

PMID- 21099201
TI  - Spinocerebellar projections from the cervical and lumbosacral enlargements in the
      chicken spinal cord.
AB  - In birds, spinocerebellar (SC) projections to the cerebellar cortex have not been
      understood well. We examined SC fiber terminal fields originating from the
      cervical and lumbosacral enlargements (CE and LSE, respectively) in the chicken.
      SC fiber terminals show parasagittal bands in the granular layer. Labeled
      terminals from the CE were distributed primarily in folia II-V and IX.
      Parasagittal bands of labeled terminals from the CE were not clearly separated in
      folia II and III but were clearly separated in folia IV and V. In folium IX,
      labeled terminals were diffusely distributed in all subfolia with no evidence of
      banding. The numbers of bands were 5 in folium II, 12 in folium III and 7 in
      folia IV and V at maximum. Labeled terminals from the LSE were distributed
      primarily in folia II-VI and IX. Labeled terminals from the LSE were arranged in
      4 bands in folium II and in 8 bands in folium III at maximum. Parasagittal bands
      from the LSE in folia IV and V were not clearly separated. In folium VI, the
      numbers of parasagittal bands was 6 at maximum. In folium IX, labeled terminals
      were mainly found in subfolium IXc forming 6-8 parasagittal bands. There were
      more parasagittal bands of labeled terminals from the CE than from the LSE. The
      topography of SC fiber terminals from the CE was different from that of SC fiber
      terminals from the LSE.

PMID- 21099202
TI  - Adult isolated congenital anterior urethrocutaneous fistula.
AB  - Isolated congenital anterior urethrocutaneous fistula (CAUF) is an extremely rare
      deformity and few cases have been reported in the English language literature.
      Moreover, adult CAUF has not been reported up to now. We present a rare adult
      patient with this unusual isolated CAUF deformity. The possible etiology and
      treatment strategy are discussed.

PMID- 21099203
TI  - Human cord blood-derived mast cells are activated by the Nod1 agonist M-TriDAP to
      release pro-inflammatory cytokines and chemokines.
AB  - Mast cells are among the first cells of our immune system to encounter exogenous
      danger. Intracellular receptors such as nucleotide-binding oligomerization domain
      (Nod) play an important role in responding to invading pathogens. Here, we have
      investigated the response of human mast cells to the Nod1 ligand M-TriDAP. Human
      cord blood-derived mast cells (CBMCs) were activated with M-TriDAP alone, or in
      combination with the Toll-like receptor (TLR) ligands lipopolysaccharide (LPS)
      and zymosan. Release of pro-inflammatory chemokines and cytokines was measured by
      ELISA, cytometric bead array and LUMINEX, and degranulation was evaluated by
      analysis of histamine release. M-TriDAP induced a dose-dependent release of IL-8,
      MIP-1alpha, MIP-1beta and TNF. In contrast, degranulation could not be observed.
      When cells were treated with M-TriDAP in combination with the TLR4 agonist LPS,
      but not with TLR2 agonist zymosan, the secretion of cytokines was augmented. We
      here present results demonstrating that human CBMCs are stimulated by the Nod1
      agonist M-TriDAP alone and in combination with LPS to produce pro-inflammatory
      cytokines and chemokines. Our results add to the concept that mast cells
      constitute an important part of our host defense, as they are equipped with
      several types of important pattern recognition receptors, including TLRs and Nod.

PMID- 21099204
TI  - Extracorporeal management of acute lung disease.

PMID- 21099205
TI  - Bactericidal activity of mouse alpha-defensin cryptdin-4 predominantly affects
      noncommensal bacteria.
AB  - Mouse Paneth cell alpha-defensins, termed cryptdins, are secreted into the
      intestinal lumen, have microbicidal activity, and contribute to intestinal innate
      immunity. Among them, cryptdin-4 (Crp4) has the most potent microbicidal
      activity. In the intestinal lumen, commensal bacteria colonize and elicit
      beneficial effects in the host. However, the effects of Crp4 against commensal
      bacteria are poorly understood. Thus, we investigated the bactericidal activities
      of Crp4 against commensal bacteria compared to noncommensal bacteria. Oxidized
      Crp4 showed only minimal or no bactericidal activity against 8 out of 12
      commensal bacterial species, including Bifidobacterium bifidum and Lactobacillus
      casei. We further addressed a role of the conserved disulfide bonds of Crp4 by
      analyzing reduced Crp4 (r-Crp4). r-Crp4 demonstrated significantly greater
      bactericidal activities against 7 of 12 commensal bacteria than did oxidized
      Crp4. Oxidized Crp4 and r-Crp4 elicited equivalently potent bactericidal
      activities against 11 of the 11 noncommensal bacteria tested, such as Salmonella
      enterica serovar Typhimurium,and against 5 of 12 commensal bacteria. Furthermore,
      when r-Crp4 was exposed to a processing enzyme of cryptdins, i.e. MMP-7, r-Crp4
      was degraded and the bactericidal activities disappeared. These findings suggest
      that Crp4 has selective bactericidal activities against intestinal microbiota and
      that the activities are dependent on the disulfide bonds.

PMID- 21099206
TI  - The chromosomal distribution of microsatellite repeats in the genome of the wolf
      fish Hoplias malabaricus, focusing on the sex chromosomes.
AB  - Distribution of 12 mono-, di- and tri-nucleotide microsatellites on the
      chromosomes of 2 karyomorphs with 2 distinct sex chromosome systems (a simple
      XX/XY - karyomorph B and a multiple X(1)X(1)X(2)X(2)/X(1)X(2)Y - karyomorph D) in
      Hoplias malabaricus, commonly referred to as wolf fish, was studied using their
      physical mapping with fluorescence in situ hybridization (FISH). The distribution
      patterns of different microsatellites along the chromosomes varied considerably.
      Strong hybridization signals were observed at subtelomeric and heterochromatic
      regions of several autosomes, with a different accumulation on the sex
      chromosomes. A massive accumulation was found in the heterochromatic region of
      the X chromosome of karyomorph B, whereas microsatellites were gathered at
      centromeres of both X chromosomes as well as in corresponding regions of the neo
      Y chromosome in karyomorph D. Our findings are likely in agreement with models
      that predict the accumulation of repetitive DNA sequences in regions with very
      low recombination. This process is however in contrast with what was observed in
      multiple systems, where such a reduction might be facilitated by the chromosomal
      rearrangements that are directly associated with the origin of these systems.

PMID- 21099207
TI  - Analysis of gene function in cultured embryonic mouse gonads using nucleofection.
AB  - Mammalian sex determination is a dynamic process involving balanced gene
      expression leading to the development of either a testis or an ovary. Candidate
      sex-determining genes have been identified through microarray-based studies of
      gonadal gene expression; however, few methods exist for validation. This study
      describes a new technique for transfecting gonads using nucleofection. Fifteen
      micrograms of expression plasmid DNA was transfected into E11.5 gonads, cultured
      for 3 days and gene expression analyzed. Following optimization, we consistently
      achieved cell transfection efficiencies of 11% of cells using pMax-GFP plasmid.
      To test the applicability of nucleofection to studies of gene function, a testis
      determining gene was transfected into gonads and its ability to sex-reverse was
      examined. When Sry was transfected into female (XX) gonads, upregulation of its
      target gene Sox9 was observed, as well as a downregulation of the ovarian gene
      Foxl2. Conversely, when shSox9 was introduced into male (XY) gonads, reduction of
      Sox9 and its target gene, Amh was observed, with a concomitant upregulation of
      Foxl2. Nucleofection-based gene delivery can recapitulate in vivo events of
      gonadal development that demonstrates 'proof-of-principle' of the method as a
      screening tool to evaluate the cellular function of potential sex-determining and
      gonadal differentiation genes.

PMID- 21099208
TI  - Synteny conservation of chicken macrochromosomes 1-10 in different avian lineages
      revealed by cross-species chromosome painting.
AB  - Cross-species chromosome painting can directly visualize syntenies between
      diverged karyotypes and, thus, increase our knowledge on avian genome evolution.
      DNA libraries of chicken (Gallus gallus, GGA) macrochromosomes 1 to 10 were
      hybridized to metaphase spreads of 9 different species from 3 different orders
      (Anseriformes, Gruiformes and Passeriformes). Depending on the analyzed species,
      GGA1-10 delineated 11 to 13 syntenic chromosome regions, indicating a high degree
      of synteny conservation. No exchange between the GGA macrochromosome complement
      and microchromosomes of the analyzed species was observed. GGA1 and GGA4 were
      distributed on 2 or 3 chromosomes each in some of the analyzed species,
      indicating rare evolutionary rearrangements between macrochromosomes. In all 6
      analyzed species of Passeriformes, GGA1 was diverged on 2 macrochromosomes,
      representing a synapomorphic marker for this order. GGA4 was split on 2
      chromosomes in most karyotypes, but syntenic to a single chromosome in blackcap
      (Passeriformes). GGA5/10 and also GGA8/9 associations on chromosomes were found
      to be important cytogenetic features of the Eurasian nuthatch (Passeriformes)
      karyotype. Fusion of GGA4 and GGA5 segments and of entire GGA6 and GGA7,
      respectively, was seen in the 2 analyzed species of Gruiformes. Consistent with
      the literature, our inter-species chromosome painting demonstrates remarkable
      conservation of macrochromosomal synteny over 100 million years of avian
      evolution. The low rate of rearrangements between macrochromosomes and the
      absence of detectable macrochromosome-microchromosome exchanges suggests a
      predominant role for rearrangements within the gene-dense microchromosome
      complement in karyotypic diversification.

PMID- 21099210
TI  - An intergenerational approach in promoting balance and strength for fall
      prevention: evidence-based or evidence-inspired?
AB  - Recently, Granacher et al. (2010) proposed an intergenerational approach to
      promoting balance and strength for fall prevention in children and elderly
      subjects together. Although this sounds like a stimulating idea, its
      effectiveness for fall prevention in both groups has yet to be demonstrated.
      Undoubtedly, fall prevention remains a big challenge to scientists and health
      professionals. The idea of implementing prevention programs on an
      intergenerational basis will probably have to undergo a complex and long-lasting
      evaluation process before a firm conclusion about its effectiveness can be made.

PMID- 21099209
TI  - Hypothalamic sites of leptin action linking metabolism and reproduction.
AB  - A critical amount of energy reserve is necessary for puberty initiation, for
      normal sexual maturation and maintenance of cyclicity and fertility in females of
      most species. Therefore, the existence of circulating metabolic cues which
      directly modulate the hypothalamus-pituitary-gonad axis is predictable. The
      adipocyte-derived hormone leptin is one of these cues having been studied
      extensively in the context of regulating the reproductive physiology. Humans and
      mice lacking leptin (ob/ob) or leptin receptor (LepR, db/db) are infertile.
      Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty
      and restores fertility. LepR is expressed in brain, pituitary gland and gonads,
      but studies using genetically engineered mouse models determined that the brain
      plays a major role. Recently, it has been made clear that leptin acts indirectly
      on gonadotropin-releasing hormone (GnRH)-secreting cells via actions on
      interneurons. However, the exact site(s) of leptin action has been difficult to
      determine. In this review, we discuss the recent advances in the field focused on
      the identification of potential site(s) or specific neuronal populations involved
      in leptin's effects in the neuroendocrine reproductive axis.

PMID- 21099211
TI  - Ox brain versus rabbit brain thromboplastin assays are the best tool for a
      preliminary diagnosis of the Arg304Gln factor VII defect (FVII Padua).
AB  - Factor VII (FVII) deficiency, the most frequent defect among the rare bleeding
      disorders, is commonly divided into type I and type II. In the former, there is a
      concomitant decrease in FVII activity and antigen. In the latter, there is a
      clear discrepancy between activity which is low and antigen which is normal or
      nearly normal. FVII Padua (Arg304Gln) is characterized by different reactivity
      towards different tissue thromboplastins. FVII levels were assayed by the use of
      different tissue thromboplastins, namely rabbit brain, human placenta, human
      recombinant and ox brain thromboplastin, in 6 homozygous patients. Cases reported
      in the literature were also evaluated. Ox brain thromboplastins yielded normal
      values, whereas human tissue or recombinant human thromboplastins yielded only
      slightly higher levels of activity than those obtained with rabbit brain
      reagents. The ox brain versus rabbit brain ratio was about 22, whereas the ratio
      for human placenta or human recombinant versus rabbit brain thromboplastin was
      only about 5. The FVII antigen versus rabbit brain, human tissue and ox brain
      activity ratios were 24.8, 4.3 and 1.1, respectively. These results indicate that
      the ox brain versus the rabbit brain thromboplastin ratio supplies a wider
      difference than the one between human tissue and rabbit brain. The antigen/ox
      brain activity ratio of 1.1 fully confirms this assertion.

PMID- 21099212
TI  - Plerixafor enables successful hematopoietic stem cell collection in an
      extensively pretreated patient with testicular cancer.
AB  - Plerixafor is a reversible CXCR4 antagonist that leads to a rapid release of
      hematopoietic stem and progenitor cells (HPSCs) from the bone marrow into the
      peripheral blood by interfering with the CXCL12-CXCR4 interaction. Based on two
      multicenter phase III studies, plerixafor in combination with granulocyte colony
      stimulating factor (G-CSF) was approved by the Food and Drug Administration for
      autologous HPSC mobilization in patients with multiple myeloma and non-Hodgkin's
      lymphoma. We report the case of a 26-year-old man with testicular cancer who was
      extensively pretreated and failed to mobilize a sufficient number of HPSCs after
      cytotoxic chemotherapy and the administration of G-CSF and pegylated G-CSF (PEG-G
      CSF). Using a combination of plerixafor, G-CSF and PEG-G-GSF after chemotherapy,
      a sufficient number of HPSCs could be collected for the support of 3 sequential
      high-dose therapies. The patient achieved a complete and uncomplicated
      engraftment following each cycle of HPSC-supported high-dose therapy. Patients
      suffering from advanced germ cell cancer may be another group that benefits from
      the use of plerixafor, which to date has only been approved for the treatment of
      multiple myeloma and lymphoma. To our knowledge, this is the first case report of
      successful mobilization of HPSCs with plerixafor in a patient with testicular
      cancer.

PMID- 21099213
TI  - The significance of bone marrow involvement in aggressive lymphomas: A
      retrospective comparison of clinical outcomes between peripheral T cell lymphoma
      and diffuse large B cell lymphoma in China.
AB  - BACKGROUND: Peripheral T cell lymphomas (PTCL) have been demonstrated to have a
      poorer prognosis than diffuse large B cell lymphoma (DLBCL) due to a high
      frequency of bone marrow involvement (BMI). However, the clinical characteristics
      of PTCL with BMI have not been fully described, and the clinical outcomes of PTCL
      with BMI and DLBCL with BMI have not been well compared. METHODS: The clinical
      characteristics and survival of 25 nodal PTCL cases with BMI and 42 DLBCL cases
      with BMI were compared. RESULTS: Most of the PTCL patients with BMI had
      lymphadenopathy (88%), B symptoms (76%), an elevated LDH level (68%), anemia
      (64%), splenomegaly (60%), and a poor performance status (52%). Except for the
      differences of lymphadenopathy and thrombocytopenia between PTCL with BMI and
      DLBCL with BMI, similarities in gender, age, hepatomegaly, splenomegaly, a bulky
      mass, B symptoms, elevated LDH, >=2 extranodal sites, ECOG scores >=2, anemia,
      and international prognostic index (IPI) and age-adjusted IPI scores were
      observed between the 2 groups. The 2 groups also had similar 3-year overall
      survival (25.8 vs. 30.0%, p = 0.846) and progressive-free survival (21.3 vs.
      25.2%, p = 0.815) rates. CONCLUSIONS: PTCL with BMI have a similar aggressive
      course and poor survival compared to DLBCL with BMI. Thus, the immunophenotype of
      either T or B lineage may not be a crucial prognostic indicator of survival for
      these 2 aggressive lymphomas.

PMID- 21099214
TI  - The use of anti-human T lymphocyte porcine immunoglobulin and cyclosporine a to
      treat patients with acquired severe aplastic anemia.
AB  - OBJECTIVE: To evaluate the treatment efficacy and tolerance of anti-human T
      lymphocyte porcine immunoglobulin (p-ALG) plus cyclosporine A (CsA) in acquired
      severe aplastic anemia (SAA). METHOD: Forty-eight SAA patients [31 males and 17
      females; 17 with very SAA (VSAA)] were treated with p-ALG plus CsA and were
      analyzed retrospectively according to early mortality, response rate and quality,
      survival rate, toxicity, and complications. They were stratified further by
      gender, age, disease severity, interval from diagnosis to treatment, and
      preexisting infections. RESULT: The median age was 28 years (range 13-64). The
      interval from diagnosis to treatment was 45 days. The median neutrophil count was
      0.178 * 109/l. The overall response was 83.3% (54.2% complete and 29.2% partial)
      with a 90-day median time (range 23-380), and 10.4% died of infection within 30
      days. The 1.5-year survival was 87.5%. vSAA patients had less response, a higher
      early mortality, and less survival (64.7, 29.4, 51.8%) compared to SAA patients
      (93.5, 0, and 100%, respectively; p < 0.05). Groups with different age, gender,
      intervals between diagnosis and treatment, and preexisting infections had the
      same response. Mild toxicities were observed. CONCLUSION: p-ALG plus CsA is a
      reliable and well-tolerated treatment for SAA, and it has the great advantage of
      a much lower cost compared to horse/rabbit ATG. VSAA was a poor predictive factor
      for the response rate.

PMID- 21099215
TI  - Plasma glial fibrillary acidic protein levels in a child with sickle cell disease
      and stroke.
AB  - A 12-year-old boy with HbSS sickle cell disease (SCD) was admitted with an acute
      febrile illness and developed overt stroke 3 days later. Plasma glial fibrillary
      acidic protein levels were elevated, as compared to pediatric controls, 32 h
      prior to the clinical diagnosis of stroke, peaked immediately prior to the
      exchange transfusion, and remained elevated 1 year later despite chronic
      transfusion therapy. Stroke in SCD can occur in the setting of acute illness, and
      a biomarker that could predict the onset and triage ill children to therapeutic
      intervention more quickly would be useful.

PMID- 21099216
TI  - High-mobility group box protein 1: a novel mediator of inflammatory-induced renal
      epithelial-mesenchymal transition.
AB  - BACKGROUND: high-mobility group box protein 1 (HMGB-1) is a chromatin-binding
      protein that bends DNA, thereby facilitating gene transcription. HMGB-1 has also
      been observed as an extracellular secreted protein in serum of patients with
      sepsis and has putative intracellular signalling effects regulating the
      production of interleukin-1 and tumour necrosis factor in a number of
      inflammatory conditions. METHODS: we established a model of immune-mediated
      epithelial-mesenchymal transition (EMT) in human proximal tubular epithelial
      cells (PTECs). PTECs were cultured with conditioned medium containing supernatant
      from activated peripheral blood mononuclear cells (aPBMCs). The model was
      characterized using phenotypic and transcriptomic approaches and suppression
      subtractive hybridisation was performed to identify differentially regulated
      genes. RESULTS: activation of PBMCs resulted in increased secretion of HMGB-1. In
      addition, treatment of PTECs with aPBMC-conditioned medium resulted in
      significant upregulation of HMGB-1 in PTECs. Direct treatment of PTECs with
      recombinant human HMGB-1 induced alterations in epithelial morphology consistent
      with EMT including reduced E-cadherin expression, increased alpha-smooth muscle
      actin expression and enhanced cell migration. HMGB-1 effects were mediated at
      least in part by the receptor for advanced glycation end products and through
      induction of transforming growth factor-beta(1) secretion from PTECs.
      CONCLUSIONS: these results suggest that HMGB-1 is a key mediator of immune
      mediated EMT of PTECs and a potentially important signalling molecule in the
      development of renal fibrosis.

PMID- 21099217
TI  - Glucose-insulin infusion reduces kidney injury in an experimental model of
      ischemic nephropathy.
AB  - BACKGROUND/AIMS: intensive insulin therapy may reduce renal dysfunction during
      severe illness in adult patients. We evaluated the effects of insulin-glucose
      (IG) in normoglycemic rats subjected to ischemia-reperfusion (I/R)-induced acute
      kidney injury. METHODS: animals received intravenous infusions of 5% glucose
      [control (C)] or IG for 96 h. I/R was induced by means of bilateral renal artery
      clamping for 45 min. Serum creatinine (sCr) and urea (sUr) levels were evaluated
      before and up to 72 h after injury. Tissue samples were evaluated 72 h after I/R
      on a scale of 0 (normal) to 4 (above 75%) in relation to the extent of kidney
      injury. RESULTS: after 48 h of I/R, sCr and sUr were increased 2- to 4-fold in C
      as compared to sham-operated controls (p < 0.05). IG produced significant
      improvements in renal function (p < 0.05). Upon histopathological analysis, the
      IG group presented less tubular damage in comparison to the C group: level 1, 60
      versus 20%; level 2, 20 versus 30%; level 3, 20 versus 30%, and level 4, 0 versus
      20%, respectively (n = 10; p = 0.057). CONCLUSION: our results suggest that IG
      infusion attenuates the renal damage induced by severe I/R independently of blood
      glucose control. This strategy may constitute a therapeutic option for the
      prevention and treatment of ischemic renal injury.

PMID- 21099218
TI  - Older age and greater carotid intima-media thickness predict ischemic events
      associated with carotid-artery stenting.
AB  - BACKGROUND: Carotid-artery stenting (CAS) may be complicated by stroke. We aimed
      to determine predictors of procedure-related ischemic events. METHODS: We
      analyzed new ischemic lesions in diffusion-weighted MRI (DWI) after CAS in 147
      patients with symptomatic high-grade carotid stenosis. Nine covariates were
      assessed as potential risk factors for new lesions in DWI: age, gender,
      hypertension, diabetes, dyslipidemia, smoking status, severity of stenosis, side
      of intervention and carotid intima-media thickness (IMT). RESULTS: From the nine
      covariates assessed, only age and IMT were independently associated with new DWI
      lesions. An age of 68 years and an IMT of 1.5 mm gave the best separation between
      high- and low-risk populations. The subgroup of patients <68 years who had an IMT
      <=1.5 mm had the lowest rate of new DWI lesions (11.3%). This rate was greater in
      patients >=68 years (30.0%; odds ratio, OR, 3.4; 95% confidence interval, CI, 1.1
      10.8) and in patients with an IMT >1.5 mm (36.4%; OR 4.5; 95% CI 1.2-17.0) and
      was particularly high in patients aged >=68 years with IMT >1.5 mm (69.6%; OR
      18.0; 95% CI 4.8-71.9). CONCLUSIONS: Older age and greater IMT are independently
      associated with the risk of CAS-related ischemic events. This risk is
      particularly high in those patients in whom older age and greater IMT coincide.

PMID- 21099219
TI  - A cost-effectiveness analysis of docetaxel versus pemetrexed in second-line
      chemotherapy for stage IIIb or IV non-small cell lung cancer in China.
AB  - BACKGROUND: To study the cost-efficacy of docetaxel and pemetrexed as single
      agents versus platinum-based combination agents in second-line treatment of stage
      IIIb or IV non-small cell lung cancer (NSCLC) patients by evaluating
      chemotherapeutic indexes and medical costs. METHODS: Treatment responses were
      evaluated by progression-free survival (PFS), overall survival (OS),
      hematological and gastrointestinal toxicities. RESULTS: Two hundred and seven
      stage IIIb or IV NSCLC patients were recruited to this clinical observation
      retrospective study. Thirty-four subjects were treated with docetaxel (group A),
      98 with platinum-based doublet chemotherapy with docetaxel (group B), 42 with
      pemetrexed (group C), and 33 patients with platinum-based doublet combination
      therapy with pemetrexed (group D). The average PFS of groups A and B was 3.28 and
      4.58 months, respectively (p = 0.042). The mean PFS of groups C and D was 3.1 and
      4.98 months, respectively (p = 0.017). The mean OS of these groups was 12.88,
      13.17, 12.40 and 13.04 months, respectively, without significant differences. The
      total medical costs in these four groups amounted to USD 5,533, 7,745, 8,569 and
      15,291, respectively. CONCLUSIONS: Platinum-based doublet chemotherapy with
      docetaxel or pemetrexed could significantly increase PFS, however, without
      significant OS improvement in comparison with using them as single agents. The
      medical expenses associated with doublet therapy were much higher than those
      associated with single therapy with a significant portion of the medical expenses
      spent on treating hematological and gastrointestinal toxicity.

PMID- 21099220
TI  - Surveillance of antimicrobial susceptibility among bacterial isolates from
      intensive care unit patients of a tertiary-care university hospital in Iran: 2006
      2009.
AB  - BACKGROUND: This study was conducted to determine the antimicrobial
      susceptibility patterns among common pathogens in the intensive care unit (ICU)
      of a university hospital in Iran between 2006 and 2009. METHODS: The isolates
      cultured in appropriate media and antimicrobial susceptibility were determined by
      disk diffusion tests according to the guidelines of the Clinical and Laboratory
      Standards Institute. RESULTS: A total of 606 isolates were recovered from
      respiratory (70.63%), urine (20.13%), blood (4.95%) and wound (1.82%) specimens
      of 456 patients. The most common isolates were Acinetobacter baumannii (22.4%),
      Pseudomonas aeruginosa (20.6%), Staphylococcus aureus (11.1%), Escherichia coli
      (8.3%) and Klebsiella pneumoniae (4.8%). Less than 7% of A. baumannii isolates
      were susceptible to aminoglycosides, ceftazidime, cefotaxime, imipenem, cefepime
      and ciprofloxacin. None was susceptible to piperacillin and piperacillin
      tazobactam. The susceptibility rates of P. aeruginosa to ciprofloxacin,
      gentamicin and piperacillin-tazobactam were 13.6, 17.4 and 33.3%, respectively.
      Methicillin-resistant S. aureus made up 96.2% of S. aureus isolates and was 100%
      susceptible to vancomycin and 51.9% susceptible to trimethoprim-sulfamethoxazole.
      CONCLUSION: Due to the high antimicrobial resistance in the ICU, we must focus on
      both a wiser use of antimicrobials and the prevention of infection.

PMID- 21099221
TI  - Treatment of hemodialyzed patients with sunitinib in renal cell carcinoma.
AB  - BACKGROUND: Understanding the effect of adverse events from commonly used agents
      such as sunitinib in hemodialyzed renal cell carcinoma (RCC) patients is
      important in clinical practice. Despite its clinical relevance, little
      information has been provided on the safety and toxicity profile of sunitinib
      when administered in hemodialyzed patients with RCC. METHODS: Six patients
      undergoing hemodialysis were treated with sunitinib for metastatic RCC between
      February 2007 and May 2009. We retrospectively reviewed the medical records of
      these patients and examined the administered dose of sunitinib, treatment-related
      toxicity, and the clinical response to therapy. RESULTS: The initial dose of
      sunitinib was 25 mg (cases 1 and 5), 37.5 mg (cases 2 and 3), and 50 mg (cases 4
      and 6), respectively. Toxicities greater than grade 3 were observed in cases 3
      and 6, and subsequently the dose was reduced in case 6. No patient had to stop
      sunitinib due to toxicities. Among the 6 patients, 3 (cases 2, 3, and 5) had
      disease progression after 1, 2, and 2 cycles of sunitinib, respectively. Three
      patients (cases 1, 4, and 6) had stable disease after 12, 5, and 4 cycles of
      treatment, respectively, and 2 of them (cases 4 and 6) were still on sunitinib 8
      and 7 months, respectively, after the start of treatment. CONCLUSIONS: The
      toxicity of and response to sunitinib in dialyzed patients seem to be comparable
      to those in patients with normal renal function. However, due to the limitations
      of this study, i.e. a small number of participants and lack of pharmacokinetic
      data, prospective clinical trials with pharmacokinetic studies in a larger cohort
      of patients are required.

PMID- 21099222
TI  - Emerging resistant Gram-negative aerobic bacilli in hospital-acquired infections.
AB  - The increasing emergence of serious multidrug-resistant (MDR) Gram-negative
      infections has led to a new health-care crisis. These infections predominately
      include MDR Pseudomonas aeruginosa, extended-spectrum beta-lactamase-producing
      Enterobacteriaceae and MDR Acinetobacter baumannii. These organisms are present
      in a variety of clinical settings, but there is a distinct paucity of antibiotics
      to effectively treat these infections. The increasing use of broad-spectrum
      antibiotics and lack of good stewardship have contributed to the increase in
      these MDR organisms. This review focuses on the main MDR Gram-negative infections
      contributing to the current crisis in health care, their mechanisms of resistance
      and various treatment options for empiric therapy.

PMID- 21099223
TI  - The Glasgow Prognostic Score is a good predictor of treatment outcome in patients
      with unresectable pancreatic cancer.
AB  - BACKGROUND: We analyzed the outcome of patients with advanced unresectable
      pancreatic cancer treated in our department from 2001 to 2008. METHODS: Of the 83
      patients included in this study, 50 patients received single-agent treatment with
      gemcitabine (GEM), 9 patients GEM combined with radiotherapy (GEM+R) and 24
      patients had best supportive care (BSC). We analyzed survival rates among the
      groups and risk factors for each group. RESULTS: The 3-year survival rates were
      dismal: GEM group 2.9%, GEM+R group 0% and BSC group 0%. Significant prognostic
      factors of the study were: performance status (PS), response rate and decrease in
      the CA19-9 level. Significant prognostic factors by the Cox proportional hazard
      model were the albumin level prior to treatment, CA19-9 levels before treatment,
      decrease in CA19-9 and response rate. Albumin levels and the Glasgow Prognostic
      Score (GPS) were found to be factors affecting survival in the GEM group.
      CONCLUSION: In this series of patients with unresectable pancreatic cancer, good
      PS, decrease in CA19-9 after treatment and good GPS determined prior to treatment
      were independent prognostic factors for better overall survival.

PMID- 21099225
TI  - Venous hypoxia: a poorly studied etiological factor of varicose veins.
AB  - Venous hypoxia has long been postulated as a potential cause of varicosity
      formation. This article aimed to review the development of this hypothesis,
      including evidence supporting and controversies surrounding it. Vein wall
      oxygenation is achieved by oxygen diffusing from luminal blood and vasa vasorum.
      The whole media of varicosities is oxygenated by vasa vasorum as compared to only
      the outer two-thirds of media of normal veins. There was no evidence that
      differences exist between oxygen content of blood from varicose and non-varicose
      veins, although the former demonstrated larger fluctuations with postural
      changes. Studies using cell culture and ex vivo explants demonstrated that
      hypoxia activated leucocytes and endothelium which released mediators regulating
      vein wall remodelling similar to those observed in varicosities. Venoactive drugs
      may improve venous oxygenation, and inhibit hypoxia activation of leucocytes and
      endothelium. The evidence for hypoxia as a causative factor in varicosities
      remains inconclusive, mainly due to heterogeneity and poor design of published in
      vivostudies. However, molecular studies have shown that hypoxia was able to cause
      inflammatory changes and vein wall remodelling similar to those observed in
      varicosities. Further studies are needed to improve our understanding of the role
      of hypoxia and help identify potential therapeutic targets.

PMID- 21099224
TI  - Expression of E-selectin and vascular cell adhesion molecule-1 in so-called
      'negative' appendices: first results to support the pathological diagnosis in
      borderline cases.
AB  - BACKGROUND: Since the rate of histologically 'negative' appendices still ranges
      between 15 and 20%, appendicitis in 'borderline' cases remains a challenging
      disease. As previously described, cell adhesion molecule expression correlates
      with different stages of appendicitis. Therefore, it was of interest to determine
      whether the 'negative' appendix correlated with the absence of E-selectin or
      vascular cell adhesion molecule-1 (VCAM-1). METHODS: Nineteen grossly normal
      appendices from a series of 120 appendectomy specimens from patients with
      suspected appendicitis were analysed in frozen sections for the expression of E
      selectin and VCAM-1. As control, 5 normal appendices were stained. RESULTS: This
      study showed a coexpression of E-selectin and VCAM-1 in endothelial cells in
      early and recurrent appendicitis. In patients with symptoms for less than 6 h,
      only E-selectin was detected. Cases with fibrosis and luminal obliteration were
      only positive for VCAM-1. In cases of early appendicitis with symptoms of less
      than 6 h duration, a discordance between histological and immunohistochemical
      results was found. CONCLUSIONS: This report indicates that E-selectin and VCAM-1
      expression could be useful parameters in the diagnosis of appendicitis in
      borderline cases.

PMID- 21099226
TI  - Therapeutic treatment with sustained-release platelet-rich plasma restores blood
      perfusion by augmenting ischemia-induced angiogenesis and arteriogenesis in
      diabetic mice.
AB  - OBJECTIVE: The objective of this investigation was to establish the effectiveness
      of sustained-release platelet-rich plasma (PRP) on perfusion and
      neovascularization in diabetic murine hind limb ischemia. METHODS: After surgery
      in streptozotocin-induced diabetic mice, the mice were randomly assigned to the
      following 4 experimental groups: control (C), 100 MUl of the sustained-release
      form of platelet-poor plasma (PPP), 100 MUl of the solution form of PRP (PRP
      sol), and 100 MUl of the sustained-release form of PRP (PRP-sr). Endpoint
      evaluations were: blood perfusion by laser Doppler perfusion imaging (LDPI),
      vascular density by anti-vWF, and mature vessel density by anti-smooth muscle
      actin antibody. RESULTS: This study demonstrated that a sustained release of PRP
      increases the perfusion of ischemic tissue as measured by LDPI (57 +/- 12; 56 +/-
      9; 72 +/- 7, and 98 +/- 4 for the C, PPP, PRP-sol, and PRP-sr groups,
      respectively; p < 0.05), capillary density (151 +/- 16; 158 +/- 12; 189 +/- 39,
      and 276 +/- 39 for groups C, PPP, PRP-sol, and PRP-sr, respectively; p < 0.05),
      and mature vessel density (28 +/- 2; 31 +/- 3; 52 +/- 10, and 85 +/- 13 for the
      C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05). CONCLUSION: A
      sustained release of PRP containing potent angiogenic growth factors restores
      blood perfusion by stimulating angiogenesis and arteriogenesis.

PMID- 21099227
TI  - Endotoxin induces differentiated contractile responses in porcine pulmonary
      arteries and veins.
AB  - BACKGROUND/AIMS: Sepsis-induced lung injury is characterized by pulmonary
      hypertension, edema and deteriorated gas exchange. As in vivo studies have
      indicated that bacterial endotoxin predominantly induces a pulmonary venous
      constriction, we aimed to investigate effects of endotoxin on isolated porcine
      pulmonary vessels. METHODS: Pulmonary arteries and veins were examined using in
      vitro isometric force recordings. Endothelin-receptor protein expression and
      distribution were analyzed by Western blot and immunohistochemistry. Freshly
      isolated preparations and vessels incubated (24 h) with/without endotoxin (10
      MUg.ml(-1)) were compared. The contractile responses to phenylephrine, UK14.304,
      U46619, PGF(2alpha), endothelin-1 (ET-1) and sarafotoxin were recorded, as well
      as the relaxation in response to acetylcholine, isoproterenol and nitroprusside.
      RESULTS: In freshly isolated vessels, phenylephrine-induced contractions had a 5
      times larger amplitude in arteries than in veins. The amplitude of the
      contractions in response to sarafotoxin was nearly 2 times larger in veins than
      in arteries, but there was no difference in responses to ET-1. Endotoxin markedly
      reduced phenylephrine-induced contractions in both arteries and veins, whereas
      the responses to ET-1 and sarafotoxin were augmented in veins only. No apparent
      changes in ET receptor expression or distribution were detected with Western blot
      or immunohistochemistry. CONCLUSION: Endotoxin differentially and selectively
      alters the contractile responses of porcine pulmonary vessels in vitro, towards a
      situation where the alpha-1 adrenergic responses of arteries are attenuated and
      the ET responses of veins are augmented. In situations with high adrenergic
      activity and high circulating ET levels, such as sepsis, these results may
      provide a mechanism contributing to pulmonary hypertension and edema formation.

PMID- 21099228
TI  - Arterial calcification is driven by RAGE in Enpp1-/- mice.
AB  - BACKGROUND/AIMS: Ectopic osteochondral differentiation, driven by ENPP1-catalyzed
      generation of the chondrogenesis and calcification inhibitor inorganic
      pyrophosphate (PP(i)), promotes generalized arterial calcification of infancy.
      The multiligand receptor for advanced glycation end-products (RAGE), which
      promotes atherosclerosis and diabetic cardiovascular and renal complications,
      also mediates chondrocyte differentiation in response to RAGE ligand calgranulins
      such as S100A11. Here, we tested RAGE involvement in ENPP1 deficiency-associated
      arterial calcification. METHODS: Because ectopic artery calcification in Enpp1-/-
      mice is P(i)-dependent and mediated by PP(i) deficiency, in vitro studies on
      effects of S100A11 and RAGE on mouse aortic explants were conducted using
      exogenous P(i), as well as alkaline phosphatase to hydrolyze ambient PP(i).
      RESULTS: S100A11 induced cartilage-specific collagen IX/XI expression and
      calcification dependent on RAGE in mouse aortic explants that was inhibited by
      the endogenous RAGE signaling inhibitor soluble RAGE (sRAGE). Enpp1-/- aortic
      explants demonstrated decreased P(i)-stimulated release of sRAGE, and increased
      calcification and type IX/XI collagen expression that were suppressed by
      exogenous sRAGE and by Rage knockout. Last, Rage knockout suppressed spontaneous
      aortic calcification in situ in Enpp1-/- mice. CONCLUSION: Cultured Enpp1-/-
      aortic explants have decreased P(i)-stimulated release of sRAGE, and RAGE
      promotes ectopic chondrogenic differentiation and arterial calcification in Enpp1
      /- mice.

PMID- 21099229
TI  - A role for all-trans-retinoic acid in the early steps of lymphatic vasculature
      development.
AB  - The molecular mechanisms that regulate the earliest steps of lymphatic vascular
      system development are unknown. To identify regulators of lymphatic competence
      and commitment, we used an in vitro vascular assay with mouse embryonic stem cell
      derived embryoid bodies (EBs). We found that incubation with retinoic acid (RA)
      and, more potently, with RA in combination with cAMP, induced the expression of
      the lymphatic competence marker LYVE-1 in the vascular structures of the EBs.
      This effect was dependent on RA receptor (RAR)-alpha and protein kinase A
      signaling. RA-cAMP incubation also promoted the development of CD31+/LYVE
      1+/Prox1+ cell clusters. In situ studies revealed that RAR-alpha is expressed by
      endothelial cells of the cardinal vein in ED 9.5-11.5 mouse embryos. Timed
      exposure of mouse and Xenopus embryos to excess of RA upregulated LYVE-1 and
      VEGFR-3 on embryonic veins and increased formation of Prox1-positive lymphatic
      progenitors. These findings indicate that RA signaling mediates the earliest
      steps of lymphatic vasculature development.

PMID- 21099230
TI  - Hyperuricemia attenuates aortic nitric oxide generation, through inhibition of
      arginine transport, in rats.
AB  - OBJECTIVES: Hyperuricemia provokes endothelial dysfunction (ECD). Decreased
      endothelial nitric oxide synthase (eNOS) activity is an important source of ECD.
      Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter
      for eNOS. We hypothesize that hyperuricemia inhibits arginine uptake. METHODS:
      Experiments were performed in freshly harvested aortas from untreated animals and
      rats fed with oxonic acid (hyperuricemia), and compared to hyperuricemic rats
      treated with either allopurinol, benzbromarone or arginine. RESULTS: Arginine
      transport was significantly decreased in hyperuricemia. Benzbromarone and
      arginine prevented the decrease in arginine transport in hyperuricemic rats while
      allopurinol did not. Arginine transport was significantly decreased in control
      rats treated with allopurinol. Blood pressure response to acetylcholine was
      significantly attenuated in hyperuricemic rats, an effect which was prevented in
      all other experimental groups. L-NAME inhibitable cGMP response to carbamyl
      choline was significantly decreased in hyperuricemic rats and this was completely
      prevented by both benzbromarone and arginine, while allopurinol partially
      prevented the aforementioned phenomenon. Hyperuricemia induced a significant
      increase in protein nitration that was prevented by benzbromarone, allopurinol,
      and arginine. Protein abundance of CAT-1, PKCalpha, and phosphorylated PKCalpha
      remained unchanged in all experimental groups. CONCLUSIONS: In hyperuricemia, the
      decrease in aortic eNOS activity is predominantly the result of attenuated
      arginine uptake.

PMID- 21099232
TI  - The eye as a common site for the early clinical manifestation of sarcoidosis.
AB  - AIMS: Our purpose was to detect the rate of initial manifestation of sarcoidosis
      in the eye. MATERIAL AND METHODS: We conducted a retrospective chart review in a
      sarcoidosis clinic in Germany. Ophthalmological data were obtained by using a
      standardized protocol, including the medical history, any comorbidity, onset and
      type of ocular manifestation that was evaluated by slit lamp, tonometry and
      fundoscopy. RESULTS: In the cohort of 1,800 patients (mean age 38.1 +/- 11.8
      years), diagnosis of sarcoidosis was established most commonly by bilateral hilar
      lymphadenopathy (96.2%), histopathology (46.9%) or other organ manifestations.
      The initial clinical presentation of sarcoidosis (mean age 34.1 +/- 10.8 years)
      had often been eye manifestation (21.2%). Within this group, anterior uveitis was
      most common (76.4%), followed by intermediate (17.3%) and posterior uveitis
      (4.7%). CONCLUSIONS: The eye is commonly the first site for manifestation of
      sarcoidosis. Ophthalmologists have a critical role in establishing the diagnosis
      of sarcoidosis.

PMID- 21099231
TI  - Aortic adventitial fibroblasts participate in angiotensin-induced vascular wall
      inflammation and remodeling.
AB  - BACKGROUND/AIMS: The role of adventitial fibroblasts in the vascular inflammation
      observed in the adventitia of large vessels in numerous cardiovascular diseases
      remains unclear. Our objective was to explore the contribution of these cells to
      angiotensin II (Ang II)-induced aortic inflammation and adventitial expansion.
      METHODS: Cytokine production by primary human aortic adventitial fibroblasts
      (AoAF) in tissue culture was detected using multiplex ELISA, and increases in
      cytokine mRNA following Ang II stimulation were quantitated by real-time PCR. The
      ability of AoAF-derived MCP-1 to attract monocytes was studied in vitro using
      Boyden assays, and the resulting effect of the monocyte-AoAF interaction on
      fibroblast proliferation was measured in vitro using proliferation and (3)H
      thymidine incorporation assays. Ang II-induced fibroblast proliferation was
      measured in vivo using aortic digestion of single cells followed by flow
      cytometric quantification of fibroblast numbers as well as fibroblast and PCNA
      immunostaining. The ability of monocytes to induce AoAF proliferation was
      demonstrated in vivo using CCR2(+/+) wild-type monocyte adoptive transfer into
      Ang II-stimulated CCR2-null mice which can produce MCP-1 but have cells lacking
      the MCP-1 receptor - CCR2. RESULTS: AoAF constitutively secreted numerous
      proinflammatory cytokines, particularly IL-6 and MCP-1, whose gene expressions
      were further upregulated in response to Ang II stimulation. AoAF-derived MCP-1
      was potent in recruiting THP-1 monocytes in vitro, and these monocytes stimulated
      AoAF proliferation based on a flow cytometric assessment of cell number and (3)H
      thymidine incorporation in tissue culture. In vivo, Ang II induced fibroblast
      proliferation, increased fibroblast and PCNA adventitial staining, and blunted
      inflammatory responses in the CCR2(-/-) background. Injection of CCR2(+/+)
      monocytes into Ang II-treated CCR2(-/-) mice restored adventitial thickening
      which resulted in increased fibrosis secondary to adventitial fibroblast
      proliferation. CONCLUSIONS: Our results suggest that Ang II-stimulates AoAF to
      recruit monocytes via fibroblast-derived MCP-1, and the recruited monocytes
      further activate fibroblast proliferation, adventitial thickening, and additional
      cytokine production. This fibroblast-monocyte amplification loop may critically
      mediate hallmarks of adventitial inflammation common to many cardiovascular
      diseases.

PMID- 21099233
TI  - [A case of adrenal hemangioma misdiagnosed as a pancreatic tail tumor].

PMID- 21099234
TI  - [Clinical characteristics of autoimmune pancreatitis].
AB  - Korean autoimmune pancreatitis (AIP) criteria 2007 was aimed to diagnose the wide
      spectrum of AIP with high sensitivity. The most crucial issue when caring for
      patients with suspected AIP is to differentiate AIP from pancreatic cancer.
      Pancreatic cancer can be distinguished from AIP by pancreatic imaging,
      measurement of serum IgG4 levels, endoscopic ultrasound guided fine needle
      aspiration and trucut biopsy, and steroid trial. Autoimmune pancreatitis is a
      rare systemic fibroinflammatory disease which can affect not only the pancreas,
      but also a variety of organs such as the bile ducts, salivary glands,
      retroperitoneum, and lymph nodes. Organs affected by AIP have a lymphoplasmacytic
      infiltrate rich in IgG4-positive cells. This inflammatory process responds
      dramatically to oral steroid therapy. Granulocytic epithelial lesion (GEL)
      positive AIP patients differ from GEL negative AIP patients in clinical features
      such as equal gender ratio, younger mean age, no increase in serum IgG4, no
      association with extrapancreatic involvement, no relapse, and frequent
      association with inflammatory bowel disease. Further investigation is needed to
      clarify the pathogenic mechanisms including more definite serological markers for
      theses two entities.

PMID- 21099235
TI  - [Clinical implications of endoscopically suspected eosinophilic esophagitis].
AB  - BACKGROUND/AIMS: We aimed to determine the concordance rate and clinical
      predictors of eosinophilic esophagitis (EoE) in patients with endoscopically
      suspected eosinophilic esophagitis (ESEoE) findings. METHODS: From June 2006 to
      December 2009 in Gangnam Severance Hospital, we prospectively enrolled the
      patients of "endoscopically suspected eosinophilic esophagitis (ESEoE)", and then
      we retrospectively reviewed and analyzed clinical features and endoscopic
      findings. RESULTS: We found 17 patients of ESEoE, and 5 of them were finally
      confirmed as an EoE by histology (diagnostic concordance rate 29.4%). We added
      two more patients previously diagnosed as EoE and compared patients of EoE+ (n=7)
      with EoE- (n=12). Mean age was 56.0 (range 36-70) and 51.0 (range 36-68) years
      old, respectively. In EoE+ group, there were 5 males and 2 females and 6 males
      and 6 females in EoE- group. The symptoms of EoE+ patients were dysphagia (n=5),
      food impaction (n=3), foreign body sensation in esophagus (n=2), chest pain
      (n=1), and heartburn (n=1). EoE- patients complained food impaction (n=5),
      heartburn (n=4), chest pain (n=2), foreign body sensation in esophagus (n=2), and
      dysphagia (n=1). The endoscopic findings of EoE+ patients were furrows (n=6),
      rings (n=5), exudates or nodules (n=3), and friability (n=1). EoE- patients
      showed rings (n=10) and furrows(n=7). Univariative analysis showed that 'a
      symptom of dysphagia', 'presence of exudates or nodules', 'more than 2 suggestive
      endoscopic findings' were significantly different between two groups.
      CONCLUSIONS: In ESEoE, diagnostic concordance rate was 29.4%. In addition,
      'symptom of dysphagia', 'exudates or nodules', '>= endoscopic findings' are more
      suggestive of EoE in ESEoE patients.

PMID- 21099236
TI  - [Comparison of the cut direction between gross finding, streoscopic finding, and
      pathologic mapping of endoscopic submucosal dissection Specimen].
AB  - BACKGROUND/AIMS: The correct pathologic review is very important after endoscopic
      submucosal dissection. The cut direction of specimen should be the right angle of
      the closest area between the lesion and the lateral margin for the correct
      pathologic review. The aim of this study was to evaluate the concordance of the
      gross finding and stereoscopic finding compared to the pathologic mapping in the
      setting of the cut direction. METHODS: Between December 2008 and May 2009, the
      objects were 48 specimens in 46 patients who were diagnosed with early gastric
      cancer and high grade adenoma after endoscopic submucosal dissection. The
      specimens were stained with hematoxylin and observed by the stereoscopy and
      analyzed by the image analysis system. The cut direction was divided by an angle
      of 45 degree based on the oral side of the specimen, and the cut directions of
      the gross finding, the stereoscopic finding, and the pathologic finding were
      compared. RESULTS: The concordance of the gross finding in the setting of the cut
      direction was 68% (33/48), and the kappa value was 0.626, and the concordance of
      the stereoscopic finding in the setting of the cut direction was 87% (33/48), and
      the kappa value was 0.874. The accuracy of the gross finding was significantly
      lower than that of the stereoscopic finding in the setting of the cut direction
      (p<0.05). CONCLUSIONS: The endoscopist needs the careful observation and close
      attention in the setting of the cut direction of the specimen by gross finding,
      and stereoscopic analysis may be a useful tool for decision of the cut direction.

PMID- 21099237
TI  - [Comparison between conventional 4 L polyethylene glycol and combination of 2 L
      polyethylene glycol and sodium phosphate solution as colonoscopy preparation].
AB  - BACKGROUND/AIMS: Effective bowel preparation is essential for accurate diagnosis
      of colon disease. We investigated efficacy and safety of 2 L polyethylene glycol
      (PEG) solution with 90 mL sodium phosphate (NaP) solution compared with 4 L PEG
      method. METHODS: Between August 2009 and April 2010, 526 patients were enrolled
      who visited Seoul National University Bundang Hospital for colonoscopy. We
      allocated 249 patients to PEG 4 L group and 277 patients to PEG 2 L with NaP 90
      mL group. Detailed questionnaires were performed to investigate compliance,
      satisfaction and preference of each method. Bowel preparation quality and
      segmental quality were evaluated. Success was defined as cecal intubation time
      less than 20 minutes without any help of supervisors. RESULTS: Both groups
      revealed almost the same baseline characteristics except the experience of
      operation. PEG 4 L group's compliance was lower than PEG 2 L with NaP 90 mL
      group. Success rate and cecal intubation time was not different between two
      groups. Overall bowel preparation quality of PEG 2 L with NaP 90 mL group was
      better than PEG 4 L group. Segmental bowel preparation quality of PEG 2 L with
      NaP 90 mL group was also better than PEG 4 L group in all segments, especially
      right side colon. Occurrence of hyperphosphatemia was higher in PEG 2 L with NaP
      90 mL group than PEG 4 L group. However, significant adverse event was not
      reported. CONCLUSIONS: PEG 2 L with NaP 90 mL method seems to be more effective
      bowel preparation than PEG 4 L method.

PMID- 21099238
TI  - [Clinical characteristics and gestational complications associated with acute
      hepatitis a in pregnancy].
AB  - BACKGROUND/AIMS: Acute hepatitis A was recently significant increased among women
      with gestational age in Korea. However, the clinical course and gestational
      complications have not been fully elucidated in pregnant patients with acute
      hepatitis A. We evaluated the clinical impact of acute HAV infection in
      pregnancy. METHODS: Twelve pregnant women out of 85 female patients with acute
      hepatitis A during 6 years were retrospectively reviewed. RESULTS: The median age
      of the pregnant group was 26.5 years old. The number of patient with acute
      hepatitis A were 5 cases in the 1st trimester, 3 cases in the 2nd and 4 cases in
      the 3rd. 4 cases had significant gestational complications. One case experienced
      the abortion in 1st trimester and one fetal distress was noted in 3rd trimester.
      The latter case was delivered of a low birth weight infant (2,390 g) caused by
      premature rupture of membrane in 36 weeks of gestational age. Other two cases
      experienced premature contraction and they had been required tocolytic treatment.
      But, all mothers featured full recovery from HAV infection. Except one aborted
      fetus and one premature birth, Newborn babies were not affected by maternal
      hepatitis A. CONCLUSIONS: Acute HAV infection during pregnancy may be associated
      with the risk of gestational complications. HAV serology and vaccination for
      women with gestation age should be considered at high prevalence area of acute
      hepatitis A.

PMID- 21099239
TI  - [A case of acute esophageal necrosis with gastric outlet obstruction].
AB  - Acute esophageal necrosis (AEN) is a very rare disorder typically presenting as a
      diffuse black esophageal mucosa on upper endoscopy. For this reason, AEN is often
      considered to be synonymous with 'black esophagus'. The pathogenesis of entity is
      still unknown. We report a case of AEN with duodenal ulcer causing partial
      gastric outlet obstruction. A 53-year-old man presented with hematemesis after
      repeated vomiting. The upper gastrointestinal endoscopy revealed circumferential
      black coloration on middle 315 to lower esophageal mucosa that stopped abruptly
      at the gastroesophageal junction. Pyloric ring deformity and active duodenal
      ulceration with extensive edema was observed. After conservative management with
      NPO and intravenous proton pump inhibitor, he showed clinical and endoscopic
      improvement. He resumed an oral diet on day 7 and was discharged. In our case the
      main pathogenesis of disease could be accounted for massive esophageal reflux due
      to transient gastric outlet obstruction by duodenal ulcer and following local
      ischemic injury.

PMID- 21099240
TI  - [A case of primary extragastrointestinal stromal tumor presenting as peritoneal
      dissemination].
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the
      gastrointestinal tract, but also occurs at a lower frequency in extra
      gastrointestinal regions such as omentum, mesentery, retroperitoneum and
      undefined abdominal sites. This tumor is called extragastrointestinal stromal
      tumor (EGIST). EGIST is mostly diagnosed as a cystic mass, but rarely occurs as a
      disseminated abdominal tumor. We experienced a 70-year-old man with primary EGIST
      presenting as peritoneal dissemination. Abdominal CT showed diffuse peritoneal
      thickening with a large amount of ascites, but no definite mass lesion.
      Laparoscopic biopsy was performed and histologic findings showed tumor composed
      of epithelioid cells. In the results of immunohistochemical stains, the tumor
      showed positive reactivity with CD117 (c-kit), CD34, vimentin and actin, but
      negative reactivity with desmin and S-100 protein. On account of unresectability
      and histologic parameters of malignant behavior, he was started on imatinib.

PMID- 21099241
TI  - [A case of psoriasis induced by infliximab treatment for Crohn's disease].
AB  - Infliximab, the monoclonal antibody to tumor necrosis factor, is indicated for
      refractory luminal and fistulizing Crohn's disease and rheumatoid arthritis.
      Infliximab treatment has adverse events including infusion reactions,
      opportunistic infections, and the potential for the event such as reactivation of
      latent tuberculosis. Cutaneous adverse reactions of TNF-alpha agents include skin
      rash, urticaria, pruritus, lupus-like eruption, and injection site reactions.
      Most of all, psoriasis or psoriasiform dermatitis induced by infliximab treatment
      for Crohn's disease is rarely reported in Korea. We report a case of psoriasis
      induced by infliximab treatment for Crohn's disease with a review of world
      literature.

PMID- 21099242
TI  - [A case of malarial hepatitis by Plasmodium vivax].
AB  - Malarial infection is one of the most important tropical diseases, but also
      increasing in the temperate regions. Severe malaria with organ dysfunction is
      commonly associated with Plasmodium falciparum, but rarely with Plasmodium vivax.
      Malarial hepatitis is also unusual in P. falciparum and very rare in P. vivax.
      Only 3 cases of malarial hepatitis caused by P. vivax have been reported in the
      world. Because the presence of hepatitis in malaria indicates a more severe
      illness with higher incidence of other complications and poor prognosis, malarial
      patients should be meticulously monitored for hepatic dysfunction with or without
      jaundice. We report here a case of malarial hepatitis caused by P. vivax that was
      presented by fever, general ache, nausea, fatigue, and significant elevation of
      aminotransferase and bilirubin.

PMID- 21099243
TI  - [Is streoscopic finding valuable for the pathologic diagnosis of endoscopic
      submucosal dissection specimen?].

PMID- 21099244
TI  - Biliverdin reductase A in the prevention of cellular senescence against oxidative
      stress.
AB  - Biliverdin reductase A (BLVRA), an enzyme that converts biliverdin to bilirubin,
      has recently emerged as a key regulator of the cellular redox cycle. However, the
      role of BLVRA in the aging process remains unclear. To study the role of BLVRA in
      the aging process, we compared the stress responses of young and senescent human
      diploid fibroblasts (HDFs) to the reactive oxygen species (ROS) inducer, hydrogen
      peroxide (H2O2). H2O2 markedly induced BLVRA activity in young HDFs, but not in
      senescent HDFs. Additionally, depletion of BLVRA reduced the H2O2-dependent
      induction of heme oxygenase-1 (HO-1) in young HDFs, but not in senescent cells,
      suggesting an aging-dependent differential modulation of responses to oxidative
      stress. The role of BLVRA in the regulation of cellular senescence was confirmed
      when lentiviral RNAi- transfected stable primary HDFs with reduced BLVRA
      expression showed upregulation of the CDK inhibitor family members p16, p53, and
      p21, followed by cell cycle arrest in G0-G1 phase with high expression of
      senescence-associated beta-galactosidase. Taken together, these data support the
      notion that BLVRA contributes significantly to modulation of the aging process by
      adjusting the cellular oxidative status.

PMID- 21099245
TI  - Thought-Shape Fusion in bulimia nervosa: an experimental investigation.
AB  - The aim of the present study was to experimentally investigate a cognitive
      distortion, 'Thought Shape Fusion' (TSF), in patients with bulimia nervosa (BN).
      TSF has been postulated as a specific distortion in patients with eating
      disorders and occurs when the thought about eating a forbidden food increases a
      person's estimate of her weight / shape, elicits a perception of moral wrongdoing
      and makes her feel fat. Previous psychometric measures of TSF in clinical and
      control groups, experiments eliciting TSF in a student sample and in patients
      with anorexia nervosa, all confirm a strong association between TSF and eating
      disorder psychopathology. Twenty patients diagnosed with BN participated in a
      within-participants experimental design with the aim of eliciting TSF and
      investigating further the possible effects of corrective behaviours (checking and
      mental neutralizing). Verbal analogue scales constituted the main outcome
      measures. TSF triggered a perception of moral wrongdoing, heightened levels of
      body dissatisfaction, elevated feelings of anxiety and guilt and prompted urges
      to engage in checking and mental neutralizing. Corrective behaviours
      significantly reduced the effects of the experimental procedure. Components of
      TSF are present in BN and are likely to play a mediating role in the maintenance
      of the disorder. The precise connection between TSF and BN remains to be explored
      in future clinical trials.

PMID- 21099247
TI  - Acute hyperparathyroidism and vascular thrombosis; an unrecognized association.

PMID- 21099246
TI  - Macronutrients act directly on the stomach to regulate gastric ghrelin release.
AB  - BACKGROUND: Ghrelin is a gastric secreted hormone deeply implicated in meal
      initiation and body weight regulation. This peptide is a peripheral orexigenic
      hormone with a nutritional status-dependent regulation showing a pre-pandrial
      rise and post-prandial fall pattern. A wide variety of studies have tested the
      effect of meal different nutrient composition over stomach mucosa ghrelin content
      and plasmatic ghrelin levels; nevertheless, few and non-conclusive data exist
      about the direct action of macronutrients on the stomach in order to regulate
      ghrelin secretion. The recent identification of taste receptors or chemoreceptors
      in the stomach mucosa would reinforce this paradigm. AIMS: To investigate the
      individual effect of different macronutrients (l-glutamine, lipids, and glucose)
      over gastric ghrelin secretion by using an in vitro gastric explants model.
      RESULTS: L-glutamine and intralipid emulsion act locally in the stomach
      decreasing ghrelin secretion, while no effect was found after glucose exposure.
      CONCLUSIONS: These results show for the first time that macronutrients, and
      specially amino acids and lipids, act directly in the stomach in order to
      regulate gastric ghrelin release. Consequently, the chemosensory capacity of the
      stomach, until now restricted to the oral cavity or intestine, is demonstrated.

PMID- 21099248
TI  - Relationship between exhaled nitric oxide and small airway lung function in
      normal and asthmatic children.
AB  - BACKGROUND: In children, exhaled nitric oxide (eNO) is usually confounded by
      factors such as age and height. We evaluated the relationship between eNO and
      lung function by minimizing the effects of aging and height. METHODS: In Study 1,
      the subjects comprised 738 elementary school children and junior high school
      children (aged 6 to 15 years, 366 males and 372 females). They were divided into
      two groups according to age (6-10 years and 11-15 years). A height range was
      determined by a histogram of height in each group. In Study 2, lung function,
      respiratory resistance and eNO level were measured in age- and height-limited
      groups. RESULTS: In Study 1, total of 148 younger children ranging in height from
      120 to 130 cm and 180 older children ranging in height from 148 to 158 cm
      participated in Study 2. The level of eNO among asthmatic children was higher
      than that of normal children in both the younger and the older groups. The
      decrease in forced expiratory volume in 1 second (FEV(1)) and other parameters of
      central airway resistance did not correlate with the eNO level. However, the
      small airway parameters of MMEF and V(25)/HT in older asthmatic children, and
      V(25)/HT and R(5)-R(20) in younger asthmatic children inversely correlated with
      eNO. CONCLUSIONS: Our data suggest that eNO level inversely correlates with small
      airway narrowing, and airway inflammation has a significant effect on small
      airway lung function in asthmatic school children.

PMID- 21099249
TI  - SLIT improves cedar pollinosis by restoring IL-10 production from Tr1 and
      Monocytes~IL-10 productivity is critical for becoming allergic~.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) is currently used for several
      allergic disorders and IL-10-producing regulatory T cells (Tr1) induced by SIT
      suppress allergic reactions. We investigated the relation between IL-10
      production and acquiring allergy. METHODS: A prospective study was undertaken to
      evaluate the effect of SIT on IL-10 production in T cells and other cell
      fractions in children with pollinosis. In addition, blood samples were collected
      from non-allergic healthy controls and patients with pollinosis to compare the
      levels of IL-10 production. PBMC were cultured with pollen peptides or control
      allergens, and the IL-10 production from monocyte and CD4 T cell was analyzed.
      RESULTS: Monocytes and CD4 T cells from SIT group of patients produced high
      levels of IL-10, suggesting that the induction of IL-10 is essential for inducing
      T cell tolerance. IL-10 production from monocytes and T cells was significantly
      increased in non-allergic controls compared to patients with pollinosis. This
      high IL-10 production was observed even when PBMC were stimulated with antigens
      other than pollen peptides. CONCLUSIONS: IL-10 is critical for induction of
      specific T cell tolerance, and increased production of IL-10 by monocytes and T
      cells during inflammatory responses or after SIT may influence effector cells in
      allergy. Present data implicates that the low productivity of IL-10 by monocytes
      and T cells is closely related with sensitivity to multiple allergens, and
      resistance to allergic diseases. Augmentation of constitutive IL-10 production
      from immune system is a potential therapeutic approach for allergic disorders.

PMID- 21099250
TI  - A case of microscopic polyangiitis following mycoplasma infection in a patient
      with MPO-ANCA positive pulmonary fibrosis.
AB  - BACKGROUND: Microscopic polyangiitis is a vasculitic disease that may result in a
      pulmonary renal syndrome. Anti-neutrophil cytoplasmic antibody (ANCA) associated
      vasculitis is strongly associated with infection. CASE SUMMARY: We describe a
      case of microscopic polyangiitis that developed in a patient with MPO-ANCA
      positive pulmonary fibrosis following infection with mycoplasma. A renal biopsy
      was undertaken following the detection of microscopic hematuria during follow-up
      but no abnormal findings were evident. The MPO-ANCA titer increased following
      infection with mycoplasma pneumonia and a second renal biopsy demonstrated
      crescentic glomerulonephritis. The degree of pulmonary fibrosis was unaffected.
      DISCUSSION: The present case suggests that the mycoplasma infection triggered the
      elevation of MPO-ANCA titer and provoked glomerulonephritis in a patient with MPO
      ANCA positive IPF. This case indicates the importance of testing for MPO-ANCA at
      the time of initial diagnosis, performing urinalysis and examining the urine
      sediment during follow-up and being alert to the potential onset of vasculitis in
      cases of pulmonary fibrosis.

PMID- 21099251
TI  - Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin
      intolerant asthma.
AB  - BACKGROUND: Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a
      considerable role in the pathophysiology of aspirin-intolerant asthma (AIA).
      Saliva has recently been validated as novel, simple, and noninvasive method for
      investigating inflammation in patients with asthma. The aim of this study is to
      clarify the molecular species of CysLT in saliva and to evaluate the CysLT and
      LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT
      concentration in saliva reflects that of their corresponding urinary metabolite.
      METHODS: We preformed an analytical cross-sectional study. CysLT and LTB4
      concentrations in saliva were quantified by enzyme immunoassay (EIA) following
      purification by high-performance liquid chromatography (HPLC). RESULTS: 1. When
      analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4,
      LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups
      (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects),
      both the concentrations of CysLTs and LTB4 were significantly higher in AIA
      patients than in ATA patients and healthy subjects. 3. We found significant
      correlations between CysLT concentration and LTB4 concentration in saliva in each
      group. 4. No significant correlation was found between the concentration of LTE4
      in urine and that of CysLTs in saliva. CONCLUSIONS: In this study, we found
      higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in
      saliva from ATA patients, suggesting that the quantification of CysLT and LTB4
      concentrations in saliva may be another diagnostic strategy for AIA.

PMID- 21099252
TI  - p53 signaling and autophagy in cancer: a revolutionary strategy could be
      developed for cancer treatment.
AB  - p53 as a tumor suppressor protein has been implicated in multiple aspects of
      biological processes, including apoptosis, cell cycle arrest, senescence,
      metabolism, differentiation and angiogenesis. Recently, several studies have
      shown that p53 can induce autophagy in both transcription-dependent and 
      independent manners. Nonetheless, p53 may also inhibit autophagy. In addition,
      p53 participates in homeostatic regulation of energy metabolism, oxidative stress
      and amino acid metabolism. Although the relationship between autophagy and p53 is
      quite complicated, and has not been well elucidated, p53 may underlie key aspects
      of metabolism and cancer biology. Thus, understanding the novel functions of p53
      may allow us to develop new anticancer therapeutic approaches.

PMID- 21099253
TI  - Autophagy in endometrial carcinomas and prognostic relevance of 'stone-like'
      structures (SLS): what is destined for the atypical endometrial hyperplasia?
AB  - Autophagy, as an intracellular adaptation mechanism for oxygen and nutrient
      deprivation, is associated with tumor cell survival and aggressiveness. This was
      reaffirmed in a series of 360 endometrial carcinomas, using a standard
      immunohistochemical technique and the LC3A antibody, capable of recognizing both
      the soluble (LC3A-I) and the membrane-bound form (LC3A-II) of the protein. LC3A
      reactivity was recognized in three basic patterns-diffuse cytoplasmic,
      cytoplasmic/juxta-nuclear, and the so-called "stone-like" structures (SLS). The
      latter has emerged as the: hallmark of autophagic activity, being detected
      exclusively in endometrial carcinomas and their immediate precursor lesions,
      namely the atypical hyperplasias, albeit in small numbers. Other forms of
      hyperplasia without cytological atypia and normal endometrial tissues expressed
      only cytoplasmic staining patterns. High SLS counts, presumed to reflect
      excessive levels of autophagic activity, were associated with tumors of extremely
      poor prognosis. In contrast, a basal level of autophagic activity, as exemplified
      by the diffuse cytoplasmic and the cytoplasmic/juxta-nuclear patterns, had no
      impact on prognosis. Survival, according to tumor cell types, showed that serous
      papillary, clear cell and the high-grade endometrioid carcinomas had the worst
      prognosis compared to low-grade endometrioid carcinomas, but interestingly,
      within this tumor group, those having high-SLS counts had a much worse survival
      rate than those that did not. It is concluded that an assessment of autophagic
      activity, particularly in the form of SLS, is useful for evaluating tumor
      aggressiveness and, in the absence or an excess of SLS, it may also prove valid
      for differentiating grade 1 endometrioid adenocarcinomas from their precursor
      lesions.

PMID- 21099254
TI  - Using phase relations to identify potential mechanisms for metabolic oscillations
      in isolated beta-cell mitochondria.
AB  - There is a great deal of evidence for the existence of metabolic oscillations in
      pancreatic beta-cells. Mechanisms that have been proposed for these oscillations
      include glycolytic oscillations; oscillations due to the feedback of Ca2+ onto
      the mitochondrial inner membrane and on dehydrogenases; and oscillations
      intrinsic to the tricarboxylic (TCA) cycle or the downstream reactions of
      oxidative phosphorylation. MacDonald and co-workers (J. Biol. Chem., 278:51894
      51900, 2003) showed examples of oscillations in TCA intermediates in isolated
      mitochondria from liver cells and pancreatic beta-cells. These oscillations were
      clearly not due to oscillations in glycolysis or Ca2+ feedback. In this article
      we consider several potential mechanisms for these TCA oscillations, using
      mathematical modeling to determine the phase relations that would result between
      the citrate and NAD+ concentrations in each case. We demonstrate that negative
      feedback at only one feedback point, isocitrate dehydrogenase, produces the
      correct phase relation if oscillations are intrinsic to the TCA cycle.
      Alternatively, the correct phase relation results if oscillations are due to
      oscillations in oxidative phosphorylation feeding back onto the TCA cycle. This
      analysis shows that the observed phase relation between citrate and NAD(P) places
      strict limits on the potential mechanism for the metabolic oscillations in
      isolated mitochondria that were observed by MacDonald and co-workers.

PMID- 21099255
TI  - The role of insulin signaling in the development of beta-cell dysfunction and
      diabetes.
AB  - The peptide hormone insulin not only regulates metabolic pathways, but also
      proliferative signaling pathways. Insulin regulates cell proliferation, protein
      synthesis and gene expression in most, if not all, mammalian tissues. Extensive
      recent studies have shown that insulin also plays an important role in the
      regulation of pancreatic islet beta-cell function. In the development of
      peripheral insulin resistance leading to an increased demand for insulin
      production, increase in beta-cell mass by compensatory hyperplasia and
      hypertrophy of beta-cells and insulin output is a crucial mechanism to maintain
      euglycemia. Indeed, impaired insulin signaling in the beta-cells and increased
      beta-cell apoptosis are associated with the onset of diabetes in obese insulin
      resistant type 2 diabetes mellitus (T2DM). Studies using gene knockout approaches
      in mice have further demonstrated that the insulin signaling in the beta-cells is
      critical for mediating insulin action on them to maintain appropriate mass and
      insulin production. It is conceivable that insulin resistance, which is usually
      associated with the compensatory mechanism of hyperinsulinemia, occurring in the
      beta-cells could be a major contributor leading to increased rate of beta-cell
      death and declined beta-cell mass. It is hypothesized that a strategy to improve
      intra-islet insulin action via enhancing beta-cell responsiveness could be a
      considerable benefit in the prevention and treatment of T2DM.

PMID- 21099256
TI  - Pattern of distribution of IGF-1 and EGF in pancreatic islets of type 2 diabetic
      patients.
AB  - BACKGROUND: Growth factors such as insulin growth factor-1 (IGF-1) and epidermal
      growth factor (EGF) play important roles in the regulation of cell metabolism in
      response to different internal as well as external stimuli. It is not clear how
      Type 2 diabetes mellitus influences the expression of these growth factors in the
      endocrine pancreas. The localization of IGF-1 and EGF was analyzed to determine
      the impact of Type 2 diabetes on the pattern of distribution of these growth
      factors in pancreatic islet cells. METHODS: Pancreatic tissue samples retrieved,
      during pancreatectomy for pancreatic tumour, from patients with and without Type
      2 diabetes were paraffin embedded. The tissue samples were chosen from non
      neoplastic, clear excisional, margins. The expression of IGF-1 and EGF was
      investigated using immunofluorescence techniques. RESULTS: IGF-1- and EGF
      immunoreactive cells were observed in many cells located in the central region of
      pancreatic islets. The percentage of islet cells expressing IGF-1 and EGF
      decreased significantly (P < 0.05) in diabetic patients compared to control.
      CONCLUSION: The number of human pancreatic islet cells expressing IGF-1 and EGF
      decreased significantly after the onset of Type 2 diabetes. These growth factors
      may play a role in the function of the endocrine pancreas and in the pathogenesis
      of the diabetes mellitus.

PMID- 21099257
TI  - The direct effects of tacrolimus and cyclosporin A on isolated human islets: A
      functional, survival and gene expression study.
AB  - The use of immunosuppressive drugs in transplanted patients is associated with
      the development of diabetes, possibly due to beta-cell toxicity. To better
      understand the mechanisms leading to post-transplant diabetes, we investigated
      the actions of prolonged exposure of isolated human islets to therapeutical
      levels of tacrolimus (Tac) or cyclosporin A (CsA). Islets were isolated from the
      pancreas of multiorgan donors by enzymatic digestion and density gradient
      centrifugation. Functional, survival and molecular studies were then performed
      after 4 days of incubation with therapeutical concentrations of Tac or  CsA.
      Glucose-induced insulin secretion was significantly decreased in Tac, but not in
      CsA exposed islets, which was associated with a reduction of the amount of
      insulin granules as shown by electron microscopy. The percentage of apoptotic
      beta-cells was higher in Tac than CsA exposed islets. Microarray experiments
      followed by Gene Set Enrichment Analysis revealed that gene expression was more
      markedly affected upon Tac treatment. In conclusion, Tac and CsA affect features
      of beta-cell differently, with several changes occurring at the molecular level.

PMID- 21099258
TI  - Long-term effects of chitosan oligosaccharide in streptozotocin-induced diabetic
      rats.
AB  - Streptozotocin has been used to induce an experimental model for diabetes to
      study the activity of anti-diabetic agents. The cholesterol-lowering effect of
      chitosan makes a continued issue in the field of diabetes, but the hypoglyecemic
      effect is inconclusive to date. Unlike chitosan, the water soluble chitosan
      oligosaccharide may possess various biological properties for diabetes. The
      present study was designed to investigate the long-term effects of chitosan
      oligosaccharide in normal and streptozotocin-induced diabetic rats using glycated
      hemoglobin and C-peptide. Chitosan oligosaccharide feeding did not cause any
      harmful effect on plasma glucose as well as plasma lipid metabolism in normal
      rats, although slightly elevated triglyceride was observed. As compared with the
      diabetic control rats, effects of chitosan oligosaccharide for 12 weeks in the
      diabetic rats were summarized as follows; (1) the blood glucose concentrations
      fell significantly and it was confirmed by decreased glycated hemoglobin, (2) the
      plasma C-peptide was increased and provided elevated degree of insulin secretion,
      and (3) relatively well reconstructed pancreatic islet with beta-cells and
      additional insulin-immunolabeled cells in the pancreatic acinus and in the
      intercalated duct were observed. These results suggested that chitosan
      oligosaccharide could improve the altered blood glucose metabolism in the
      diabetic rats by various mechanisms such as accelerated proliferation or
      neogenesis of beta cells and increased secretory capacity of insulin.

PMID- 21099259
TI  - Characterisation of the NES2Y cell line and its use in the production of human
      glucose-responsive insulin producing (hGRIP) cell lines by cell-cell fusion.
AB  - Diabetes mellitus is a debilitating disease and alternative methods of treatment
      are a priority if the short-term and long term sequelae are to be avoided.  Here
      the authors manipulate NES2Y cells, which have the potential to be used as
      'fusion partners' to produce human insulin-producing glucose-responsive hybrids. 
      The fusion experiments were carried out using polyethylene glycol (PEG) and
      electroporation.  Human insulin production of the resulting hybrids (in response
      to glucose) was measured using ELISA. Our results showed that it is possible to
      engineer human glucose-responsive insulin-producing (hGRIPs) hybrid cells by the
      manipulation of two different cell types. The resulting hybrids continuously grow
      in culture and are insulin-secreting and glucose-responsive for a period of time.
      Immortalised cells with the characteristics of human beta cells could provide an
      important resource for experimental studies in Type 1 diabetes, such as an
      improved understanding of the fundamental mechanisms of glucose-responsive
      insulin processing and secretion, transplantation and drug screening programs.

PMID- 21099260
TI  - Downregulation of ZnT8 expression in pancreatic beta-cells of diabetic mice.
AB  - Zinc transporter 8 (ZnT8) has been identified as a beta-cell-specific Zinc
      transporter expressed in insulin-secretory granules. Recent genome wide
      association studies indicated that Arg325Trp polymorphism of Slc30a8 encoding
      ZnT8 is associated with susceptibility to type 2 diabetes. As a first step
      towards understanding the pathogenic role of ZnT8 in diabetes, we evaluated the
      expression of ZnT8 in mouse pancreas. A rabbit polyclonal antibody specific to
      ZnT8 was raised. The raised ZnT8 antibody reacted with mouse, rat and human ZnT8
      expressed in beta-cells without cross-reacting with other ZnTs. ZnT8 was
      expressed in alpha-, beta- and PP-cells, but not in delta-cells, in adult mouse
      islets. During mouse pancreas development, ZnT8 expression was detected as early
      as embryonic day 15.5 when beta-cells started to appear in large numbers.
      Finally, the expression level of ZnT8 was compared with pancreas of two diabetic
      model mice, db/db mice and Akita mice. In both animal models of diabetes, ZnT8
      expression was remarkably downregulated in the early stage of diabetes. As a
      conclusion, ZnT8 is expressed in multiple lineages of endocrine cells in the
      pancreas. Our findings suggest that downregulation of ZnT8 may be associated with
      impaired function of beta-cells in diabetes.

PMID- 21099261
TI  - The miR-30 family microRNAs confer epithelial phenotype to human pancreatic
      cells.
AB  - Epithelial-to-mesenchymal transition is a phenomenon necessary for embryonic
      development and also seen during certain pathological conditions.  We show here
      for the first time that reduction in miR-30 family microRNAs, is responsible for
      mesenchymal transition of primary cultures of human pancreatic epithelial cells. 
      We found that miR-30 family microRNAs target mesenchymal gene transcripts and
      maintain them in a translationally inactive state.  Forced depletion using miR-30
      family specific anti-miRs leads to mesenchymal transition while ectopic
      overexpression maintains the epithelial phenotype.  We also show that miR-30
      family microRNAs increase in abundance during differentiation of pancreatic islet
      derived mesenchymal cells into hormone-producing islet-like cell aggregates.  Our
      studies in human adult diseased pancreas also demonstrate that miR-30 family
      microRNAs are expressed at lower abundance in fibrotic lesions during
      pancreatitis.  Together, our data confirm that miR-30 family microRNAs form a
      part of the regulatory signaling events involved in cellular response of
      pancreatic epithelial cells during mesenchymal transition.

PMID- 21099262
TI  - Physiological significance of SK4 channels in pancreatic beta-cell oscillations.
AB  - Pancreatic beta-cells show oscillations in membrane potential (Vm), the cytosolic
      Ca (2+) concentration ([Ca (2+) ]c) and finally insulin secretion. It is well
      accepted that the initiation of a burst phase with action potentials is mediated
      by voltage-dependent Ca (2+) (and Na (+) ) channels. The mechanism triggering the
      onset of interburst phases is less clear. The exact nature of the K (+) channels
      that hyperpolarize Vm to maintain the rhythmic activity is unknown. In 1999 Gopel
      and co-workers (1) described a current termed Kslow and claimed that this current
      terminates the burst phases. KATP current is a part of the Kslow current. We
      could show that the Ca (2+) -dependent K (+) current through K (+) channels of
      intermediate conductance (SK4, KCa3.1 or IK1) also contributes to the Kslow
      current. We suggest that the Kslow current is composed of two currents through
      metabolism-regulated K (+) channels, KATP (regulated by ATP) and SK4 (regulated
      by Ca (2+) ). We further propose that the SK4 component of the Kslow current can
      trigger oscillations in mice without functioning KATP channels.

PMID- 21099263
TI  - beta-cell autophagy: A novel mechanism regulating beta-cell function and mass:
      Lessons from beta-cell-specific Atg7-deficient mice.
AB  - Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic
      components into the lysosome to form autophagic vacuoles for bulk protein
      degradation. While previous studies have reported enhanced autophagosome
      formation in pancreatic beta-cells under some pathophysiological conditions, the
      role of autophagy remains largely unknown. We have reported that low-level
      constitutive basal autophagy was observed in beta-cells of C57BL/6 mice fed
      standard diet; however, autophagy was markedly up-regulated in mice fed high-fat
      diet. Free fatty acids (FFAs), which can cause peripheral insulin resistance
      associated with diabetes, induced autophagy in beta-cells. Genetic inactivation
      of autophagic machinery in beta-cells resulted in reduced glucose-stimuated
      insulin secretion with progressive intracellular accumulation of ubiquitinated
      proteins and deformed mitochondria. These results suggest that the degradation of
      cellular components by basal autophagy is essential for the maintenance of normal
      architecture and function of beta-cells. We will also discuss the role of
      inductive autophagy as a crucial element of stress responses to protect beta
      cells, which supports compensatory beta-cell growth in the presence of insulin
      resistance.

PMID- 21099264
TI  - Matrix alkalinisation unleashes beta-cell mitochondria.
AB  - Recently, we have identified matrix pH as a key regulator of mitochondrial energy
      metabolism in the beta-cell (Wiederkehr et al. EMBO J. (2009) 28(4):417-28).
      Under resting glucose conditions matrix pH in beta-cell mitochondria is unusually
      low (pH 7.25). Following nutrient stimulation of rat islets matrix alkalinisation
      occurs raising matrix pH to 7.7 a value close to those determined in other cell
      types (pH 7.8-8.1). Alkalinisation follows a very similar time-course as net
      increases of the cytosolic ATP levels and is associated with a 2.5-fold elevation
      of the mitochondrial ATP synthesis rate. Suppression of this alkalinisation using
      nigericin almost completely abolishes mitochondrial ATP synthesis in a
      permeabilised cell system. Our working hypothesis is that low mitochondrial pH
      maintains the beta-cell mitochondria in an inactive state, whereas nutrient
      stimulation favors alkalinisation and full activation of mitochondrial energy
      metabolism, resulting in mitochondrial signal generation and insulin granule
      exocytosis.

PMID- 21099265
TI  - A role for autophagy in beta-cell life and death.
AB  - Autophagy is a vacuolar, self-digesting mechanism responsible for the removal of
      organelles and defined regions of the cytoplams. This process has, in general, a
      beneficial role for the cell, since it regulates the turnover of aged proteins
      and eliminates damaged structures. However, cells that undergo altered autophagy
      may be triggered to die in a non-apoptotic manner. As a matter of fact, in recent
      years it has become clear that dysregulated autophagy may be implicated in
      several disorders, such as cancer, neurodegenerative diseases and hepatic
      encephalopathy. We have recently shown that beta-cells of type 2 diabetic
      subjects show signs of autophagy associated death, which may contribute to the
      overall loss of beta-cell mass in type 2 diabetes. In addition, studies with cell
      lines and rodent models have demonstrated the importance of autophagy in beta
      cell function and survival. Altogether, the available evidence supports the view
      that autophagy is implicated in beta-cell pathophysiology, and suggests that
      addressing the molecular mechanisms involved in autophagic regulation might
      provide clues  for preventing or treating beta-cell damage in diabetes.

PMID- 21099266
TI  - The alphabetadelta of ion channels in human islet cells.
AB  - Ion channels in the plasma membrane are critical for coupling metabolic signals
      to hormone release from pancreatic islet cells. The increased availability of
      human islets for research purposes has recently enabled us to perform a more
      detailed characterization of ion channels in human beta-cells as well as in human
      delta- and alpha-cells. This addendum summarizes the major differences between
      mouse and human beta-cells and discusses some of the remaining open questions. In
      addition, differences between the ion channel complements of human beta-cells and
      islet non-beta-cells are addressed.

PMID- 21099267
TI  - Optical imaging of islets: New possibilities by the development of infrared
      fluorescent proteins.
AB  - The capacity to record the spatial and quantitative distribution of cellular
      subtypes involved in diabetogenic processes is a key element in experimental
      diabetes research. A non-invasive technique to accurately monitor parameters such
      as pancreatic beta-cell mass (BCM) and its distribution would provide a stepping
      stone in understanding different aspects of diabetes pathogenesis. It would also
      assist in the development of therapeutic regimes by providing a tool for the
      evaluation of anti-diabetic drugs or other curative or diagnostic measures. At
      present, a range of imaging modalities are being explored for this purpose.
      Whereas nuclear imaging techniques, characterised by their high tissue
      penetration depth but relatively low spatial resolution, appear most promising
      for the study of humans and large animals, optical imaging enables a route to
      cost-effective, high sensitivity, high resolution imaging in rodent models for
      disease. In this commentary, the potential impact of infrared fluorescent
      proteins (IFPs), as recently reported by Shu et al in Science, for imaging of the
      pancreas in small animals will be discussed.

PMID- 21099268
TI  - TRPM2 and pancreatic beta-cell responses to oxidative stress.
AB  - Recent reports have linked the adenine nucleotide 2nd messenger gated Ca (2+)
      channel TRPM2 with hydrogen peroxide-induced pancreatic beta-cell death in mouse
      and rat systems. As beta-cells are exposed in vivo to reactive oxygen species
      produced via the respiratory chain and NADPH oxidases (reviewed in (3, 4) ),
      these reports suggest the existence of a TRPM2-dependent signaling pathway
      involved in beta-cell responses to redox stress.

PMID- 21099269
TI  - Heavy metals, islet function and diabetes development.
AB  - It has long been believed that heavy metals possess many adverse health effects.
      Uncontrolled industrialization has released heavy metal pollution in the world.
      Heavy metal pollutants damage organ functions and disrupt physiological
      homeostasis. Diabetes mellitus is growing in prevalence worldwide. Several
      studies have indicated that the deficiency and efficiency of some essential trace
      metals may play a role in the islet function and development of diabetes
      mellitus. Some toxic metals have also been shown to be elevated in biological
      samples of diabetes mellitus patients. In the present work, we review the
      important roles of heavy metals in islet function and diabetes development in
      which the in vitro, in vivo or human evidences are associated with exposure to
      zinc, arsenic, cadmium, mercury and nickel. Through this work, we summarize the
      evidence which suggests that some heavy metals may play an important role in
      diabetes mellitus as environmental risk factors.

PMID- 21099270
TI  - Neurogenin3: a master regulator of pancreatic islet differentiation and
      regeneration.
AB  - The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3, Neurog3) is
      critical for the development of the endocrine cells of the islets. Either
      disrupted or forced expression of Ngn3 early in mouse pancreas development
      abrogates the formation of islets. The successive waves of Ngn3 expression that
      occur during the primary and secondary transitions of endocrine cell development
      temporally determine the four distinct endocrine cell lineages, alpha, beta, PP,
      and delta cells that express glucagon, insulin, pancreatic polypeptide, and
      somatostatin, respectively. During islet regeneration after injury of the adult
      mouse pancreas, such as by duct ligation or streptozotocin, Ngn3 is activated in
      duct-associated stem/progenitor cells that transform into alpha and/or beta cells
      (Xu et al, Collombat et al). The important role of Ngn3 as a master regulator of
      endocrine pancreas development directs attention to finding therapeutic
      approaches to enhance Ngn3 expression in diabetes as a means to increase beta
      cell mass and functions.

PMID- 21099271
TI  - A new collagenase blend increases the number of islets isolated from mouse
      pancreas.
AB  - Diabetes is a predominant metabolic disorder in the industrialized nations. Since
      pancreatic islets play a key role in type I and type II diabetes, the isolation
      of islets from pancreatic tissues represents an important step in diabetes
      research. However, to date, only a small fraction of all islets, resident within
      any given pancreas, are harvested by using currently available enzyme blends.
      This holds true for islet isolation from both the mouse and the human pancreas.
      In the present study, the newly developed Liberase TL Research Grade was compared
      to the widely used Liberase RI to investigate the effect of increased collagenase
      purity on islet yield. The study shows that reducing the degradation products of
      collagenases during Liberase production significantly increases the number of
      islets isolated from the mouse pancreas by 28%, and, therefore, is expected to
      lower the numbers of mice and resulting costs for diabetes research accordingly.
      Furthermore, this study also points to a possibility to increase the number and
      mass of islets isolated from human pancreases, for which only a limited donor
      pool exists.

PMID- 21099272
TI  - Acomys, the closest relatives to Gerbils, do express Pdx-1 protein and have
      similar islet morphology to Gerbils.
AB  - Acomys, also called spiny mice, were once used as a diabetes model. We have
      recently demonstrated that the closest relatives to the Acomys, members of the
      family Gerbillinae, lack the transcription factor Pdx-1. Therefore, we sought to
      determine if members of this family also lack Pdx-1, and describe the pancreatic
      morphology in three different species of Acomys: Acomys cahirinus (Egyptian spiny
      mouse), Acomys cilicicus (Asia Minor spiny mouse) and Acomys dimidiatus (eastern
      spiny mouse). We successfully cloned the Acomys Pdx-1 gene and we demonstrate by
      immunocytochemistry that the Pdx-1 protein is expressed in the pancreatic insulin
      immunoreactive cells and in a subset of the somatostatin cells. The basic islet
      structure is very similar to other rodents - with the insulin cells in the
      center, and glucagon, somatostatin, PP and occasional PYY cells in the periphery.
      No ghrelin or CART cells were identified. Nkx6.1 was localized specifically to
      the insulin immunoreactive cells, while Nkx2.2 was found in all endocrine cells
      except the somatostatin immunoreactive cells. Both MafA and MafB were expressed
      in the islets; MafA being specific for the insulin cells, while MafB was
      primarily in the glucagon cells but also found in some insulin cells. Isl-1 was
      localized in all endocrine cell types. In conclusion, the closest relatives to
      the Gerbils express a Pdx-1 protein that is 90% similar to other rodents but also
      has a unique 3 amino acid insert compared to other species.  During the evolution
      of the spiny mice and the gerbils, it appears that the Pdx-1 gene was lost.

PMID- 21099273
TI  - Control of insulin granule dynamics by AMPK dependent KLC1 phosphorylation.
AB  - The movement of insulin granules along microtubules, driven by kinesin-1/Kif5B,
      is essential for glucose-stimulated insulin secretion from pancreatic beta-cells.
      5?AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine
      kinase, which is activated in beta-cells at low glucose concentrations, but
      inhibited as glucose levels increase.  AMPK activation blocks glucose-stimulated
      recruitment of secretory granules to the cell surface and insulin secretion,
      suggesting motor proteins may be targets for this kinase. Whilst both kinesin
      1/Kif5B and kinesin light chain-1 (KLC1) contain consensus AMPK phosphorylation
      sites only a peptide corresponding to Ser520 in mouse KLC1 and purified
      recombinant GST-KLC1 were phosphorylated by purified AMPK in vitro.  To test the
      hypothesis that phosphorylation at this site may modulate kinesin-1-mediated
      granule movement, we developed a novel approach to study the dynamics of the
      granules within a cell in three-dimensions using Nokigawa spinning disc confocal
      microscopy.  This cell-wide approach revealed that the number of longer
      excursions (>10 um) increased significantly in response to elevated glucose
      concentration (30 vs 3 mM) in control MIN6 cells.  However, similar changes were
      seen in cells over-expressing wild-type KLC1, phosphomimetic (S517/520D) or non
      phosphorylatable (S517/520A) mutants of KLC1.  Moreover, no evidence for a change
      in the phosphorylation state of KLC1 at Ser520 after AMPK activation was obtained
      using an anti-phospho Ser520-specific antibody. Thus, changes in the
      phosphorylation state of KLC1 at Ser517/520 are unlikely to affect motor
      function.  In conclusion, we describe a new three-dimensional cell wide approach
      for the analysis of secretory granule dynamics in living beta-cells.

PMID- 21099274
TI  - Targeting insulin amyloid assembly by small aromatic molecules: toward rational
      design of aggregation inhibitors.
AB  - Amyloid fibril formation is a common event in more than twenty human diseases and
      in some normal physiological processes. The mechanism of this ordered aggregation
      process and the molecular forces driving it are therefore of great importance.
      One of the strategies used in this field is targeting the fibrillization process
      by different factors, like, short peptides, organic molecules, etc. Here, we
      targeted insulin fibril formation by a range of small aromatic molecules, with
      different numbers of aromatic rings and various substituent groups. Using
      Thioflavin T fluorescence assay and transmission electron microscopy, we found
      that all dicyclic and tricyclic compounds in our screen were efficient inhibitors
      of insulin fibril formation. A common notion regarding amyloid inhibitors is that
      two functional groups are essentials for interfering with the amyloid formation
      process; a recognition motif and a bulky group for inducing a steric
      interference. However, here, we showed that some monocyclic compounds as small as
      toluene were also found to inhibit fibrillization. In addition, we found that
      substituent of benzene ring have a great influence on the inhibitory potency.
      Specifically, cyano, methyl and nitro groups increased the inhibitory potency.
      The results introduced here may contribute to future rational design of amyloid
      inhibitors.

PMID- 21099275
TI  - Insulin receptor signaling for the proliferation of pancreatic beta-cells:
      involvement of Ca2+ second messengers, IP3, NAADP and cADPR.
AB  - Insulin has an autocrine/paracrine role through insulin receptors in pancreatic
      beta-cells. Herein, we show the insulin receptor signaling pathway underlying
      CD38/ADPR-cyclase activation for NAADP/cADPR formation to induce Ca2+ rise,
      ultimately resulting in beta-cell proliferation. Binding of insulin on insulin
      receptors leads to the activation of IRS/Akt/PI3K/PLC. Activation of PLC
      generates IP3 and DAG; the former induces Ca (2+) release, resulting in
      activation of CD38/ADPR-cyclase for cADPR production via cGMP-dependent mechanism
      and the latter activates PKC, resulting in activation of ADPR-cyclase for NAADP
      synthesis. The NAADP-induced Ca (2+) signal is required for IP3-induced Ca (2+)
      release from the ER. CD38 plays an important role in insulin receptor signaling
      in beta-cells by reflecting a declined sustained Ca (2+) signal, cADPR levels,
      and beta-cell proliferation in response to insulin in CD38 (-/-) islets. However,
      evidence indicates that a hitherto-unidentified ADPR cyclase in addition to CD38
      participates in insulin-induced signaling through cADPR and NAADP synthesis. In
      conclusion, insulin receptor signaling in beta-cells employs three Ca (2+)
      signaling messengers, IP3, NAADP, and cADPR through a complex but concerted
      action of signaling molecules for Ca2+ signaling, which is involved in the
      proliferation of the islets.

PMID- 21099276
TI  - Immobilization of primary cultures of insulin-releasing human pancreatic cells.
AB  - Transplantation of pancreatic islets isolated from organ donors constitutes a
      promising alternative treatment for type1 Diabetes, however, it is severely
      limited by the shortage of organ donors. Ex-vivo islet cell cultures appear as an
      attractive but still elusive approach for curing type 1 Diabetes. It has recently
      been shown that, even in the absence of fibrotic overgrowth, several factors,
      such as insufficient nutrition of the islet core, represent a major barrier for
      long-term survival of islets grafts. The use of immobilized dispersed cells may
      contribute to solve this problem due to conceivably easier nutritional and oxygen
      support to the cells.  Therefore, we set out to establish an immobilization
      method for primary cultures of human pancreatic cells by adsorption onto
      microcarriers (MCs). Dispersed human islets cells were seeded onto Cytodex1
      microcarriers and cultured in bioreactors for up to eight days. The cell number
      increased and islet cells maintained their insulin secretion levels throughout
      the time period studied. Moreover, the cells also presented a tendency to cluster
      upon five days culturing.  Therefore, this procedure represents a useful tool for
      controlled studies on islet cells physiology and, also, for biotechnological
      applications.

PMID- 21099277
TI  - Extracellular matrix proteins involved in pseudoislets formation.
AB  - Extracellular matrix proteins are known to mediate, through integrins, cell
      adhesion and are involved in a number of cellular processes, including insulin
      expression and secretion in pancreatic islets. We investigated whether expression
      of some extracellular matrix proteins were implied in islets-like structure
      formation, named pseudoislets. For this purpose, we cultured the beta-cell line,
      RINm5F, during 1, 3, 5 and 7 days of culture on treated or untreated culture
      plate to form adherent cells or pseudoislets and analysed insulin, collagen IV,
      fibronectin, laminin 5 and beta1-integrin expression. We observed that insulin
      expression and secretion were increased during pseudoislets formation. Moreover,
      we showed by immunohistochemistry an aggregation of insulin secreting cells in
      the centre of the pseudoislets. Peripheral beta-cells of pseudoislets did not
      express insulin after 7 days of culture. RT-PCR and immunohistochemistry studies
      showed a transient expression of type IV collagen in pseudoislets for the first 3
      days of culture. Study of fibronectin expression indicated that adherent cells
      expressed more fibronectin than pseudoislets. In contrast, laminin 5 was more
      expressed in pseudoislets than in adherent cells. Finally, expression of beta1
      integrin was increased in pseudoislets as compared to adherent cells. In
      conclusion, laminin 5 and collagen IV might be implicated in pseudoislets
      formation whereas fibronectin might be involved in cell adhesion. These data
      suggested that extracellular matrix proteins may enhance the function of
      pseudoislets.

PMID- 21099279
TI  - Monitoring neovascularization of intraportal islet grafts by dynamic contrast
      enhanced magnetic resonance imaging.
AB  - Fifteen thousand youths are diagnosed yearly with type 1 diabetes mellitus.
      Pancreatic islet transplantation has been shown clinically to provide short-term
      (~1 year) insulin independence. However, challenges associated with early
      vascularization of transplanted islet grafts and long-term islet survival remain.
      We utilized dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to
      monitor neovascularization of islets transplanted into the right lobe of the
      liver in a syngeneic mouse model system. The left lobe received no islets and
      served as a control. DCE data were analyzed for temporal dynamics of contrast
      (gadolinium) extravasation and the results were fit to a Tofts two-compartment
      exchange model. We observed maximal right lobe enhancement at seven days post
      transplantation. Histological examination up to 28 days was used to confirm
      imaging results. DCE-derived enhancement strongly correlated with
      immunohistochemical measures of neovascularization. To our knowledge, these
      results are the first to demonstrate using a FDA approved contrast agent that DCE
      MRI can effectively and non-invasively monitor the progression of angiogenesis in
      intraportal islet grafts.

PMID- 21099278
TI  - Impaired insulin secretion in transgenic mice over-expressing calpastatin in
      pancreatic beta-cells.
AB  - Calpains are a family of calcium-activated proteases involved in a number of
      cellular functions including cell death, proliferation and exocytosis. The
      finding that variation in the calpain-10 gene increases type 2 diabetes risk in
      some populations has increased interest in determining the potential role of
      calpains in pancreatic beta-cell function. In the present study, transgenic mice
      (Cast (RIP)) expressing an endogenous calpain inhibitor, calpastatin, in
      pancreatic beta-cells were used to dissect the role of the calpain system in the
      regulation insulin secretion in vivo and in vitro. Glucose concentrations after
      the administration of intraperitoneal glucose were significantly increased in
      Cast (RIP) mice compared with wildtype littermate controls. This was associated
      with a reduction in glucose-stimulated insulin secretion in vivo. Using pancreas
      perfusion, static islet incubation and islet perifusion, it was demonstrated that
      Cast (RIP) islets hypersecreted insulin at low glucose, but exhibited
      significantly impaired insulin responses to high glucose. Examination of insulin
      release and calcium signals from isolated islets indicated that distal components
      of the insulin exocytotic pathway were abnormal in Cast (RIP) mice. Cast (RIP)
      islets had modestly reduced expression of Rab3a and other critical components in
      the late steps of insulin exocytosis. These studies provide the first evidence
      that blocking endogenous calpain activity partially impairs insulin release in
      vivo and in vitro by targeting distal components of the insulin exocytotic
      machinery.

PMID- 21099280
TI  - CXCL10- a path to beta-cell death.
AB  - The ability of the beta-cells to control blood glucose levels depends on their
      function and mass. In both, type 1 and type 2 diabetes mellitus the main
      processes leading to beta-cell failure are apoptosis and loss of function. Many
      studies demonstrate how cytokines and chemokines have an active role in
      triggering the immune-response against the beta-cell population. In a recent
      study we have identified that the chemokine CXCL10 may play an active role in
      triggering beta-cell destruction.  We have identified the Toll like receptor 4 as
      the receptor for CXCL10 and as new pathway for the induction of beta-cell
      apoptosis. Our findings may open new therapeutic approaches to fight onset and
      progression of the disease.

PMID- 21099282
TI  - Control of secretory granule access to the plasma membrane by PI3 kinase-gamma.
AB  - The role and mechanism of phosphatidylinositol 3-OH (PI3) kinase as a regulator
      of insulin secretion is much debated. Studies employing non-selective
      pharmacological agents suggest a negative role for this key signal transduction
      enzyme in insulin release, perhaps through regulation of ATP-sensitive K (+)
      channels. There are however, three PI3 kinase families containing several kinase
      isoforms. More recent studies, including our own recently published work, have
      begun to investigate PI3 kinase isoform-specific mechanisms regulating insulin
      secretion. Building on our previous work demonstrating that mice lacking a G
      protein coupled PI3 kinase catalytic subunit (p110gamma -/-) lack first phase
      insulin secretion and display a blunted second phase of secretion, we have now
      elucidated the mechanism by which this PI3 kinase isoform acts as a positive
      regulator of insulin secretion. Using a combined molecular and pharmacological
      approach, together with biophysical assays of insulin exocytosis and cellular
      imaging, we demonstrated that p110gamma is an important modulator of insulin
      granule exocytosis and localization to the plasma membrane by modulating cortical
      actin density.

PMID- 21099281
TI  - Glucose-dependent potentiation of mouse islet insulin secretion by Epac activator
      8-pCPT-2'-O-Me-cAMP-AM.
AB  - Epac2 is a cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF) that is
      proposed to mediate stimulatory actions of the second messenger cAMP on mouse
      islet insulin secretion. Here we have used methods of islet perifusion to
      demonstrate that the acetoxymethyl ester (AM-ester) of an Epac-selective cAMP
      analog (ESCA) penetrates into mouse islets and is capable of potentiating both
      first and second phases of glucose-stimulated insulin secretion (GSIS). When used
      at low concentrations (1-10 MUM), 8-pCPT-2'-O-Me-cAMP-AM activates Rap1 GTPase
      but exhibits little or no ability to activate protein kinase A (PKA), as
      validated in assays of in vitro PKA activity (phosphorylation of Kemptide), Ser
      (133) CREB phosphorylation status, RIP1-CRE-Luc reporter gene activity, and PKA
      dependent AKAR3 biosensor activation. Since quantitative PCR demonstrates Epac2
      mRNA to be expressed at levels ca. 5.3-fold greater than that of Epac1, available
      evidence indicates that Epac2 does in fact mediate stimulatory actions of cAMP on
      mouse islet GSIS.

PMID- 21099283
TI  - Expression and function of Set7/9 in pancreatic islets.
AB  - Histone tail acetylation and methylation are known to enhance accessibility of
      islet genes to transcription factors and the basal transcriptional machinery.  In
      this brief report, we follow up on a recent study in which we identified the
      islet enriched factor Set7/9 as a potentially important histone methyltransferase
      in beta-cells (Deering, et al. Diabetes 2009; 58:185-93).  We had suggested that
      the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene
      to the basal transcriptional machinery.  Consistent with this hypothesis, we show
      here that RNA polymerase II occupancy at the insulin and IAPP genes is
      considerably enhanced in beta-cells compared to alpha cells (or NIH3T3 cells),
      and that the converse is true for RNA polymerase II occupancy at the glucagon
      gene. The enrichment of Set7/9 in beta-cells appears to be dependent upon Pdx1,
      as knockdown of Pdx1 in INS-1 beta-cells using small hairpin RNAs almost
      completely abolishes Set7/9 expression.  A LacZ expression vector driven by the 
      6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows
      beta-cell-line-specific expression.  Taken together, our data support further the
      hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing
      chromatin accessibility and transcription of beta-cell genes.

PMID- 21099284
TI  - Insulin modulation of glucagon secretion: the role of insulin and other factors
      in the regulation of glucagon secretion.
AB  - Glucagon plays a critical counter-regulatory role to insulin to maintain optimal
      glucose homeostasis. Glucagon secretion from pancreatic alpha-cells is regulated
      by glycemia, neural input, and secretion from neighboring beta-cells. Recently,
      we provided direct genetic evidence of a critical role for insulin signaling in
      the regulation of glucagon secretion in vivo. Pancreatic alpha-cell targeted
      disruption of insulin receptor expression in mice resulted in glucose
      intolerance, hyperglycemia and hyperglucagonemia coupled with an abnormal
      glucagon response to hypoglycemia. Furthermore, streptozotocin treated mice
      exhibited paradoxically increased plasma glucagon suggesting a dominant role for
      insulin in the regulation of glucagon secretion compared with glucose. In fact,
      normalization of hyperglycemia by phrolidzin treatment decreased plasma glucagon
      levels suggesting a stimulatory effect of glucose on glucagon secretion and also
      revealed the significance of insulin in hyperglycemic states. Together these
      studies provide novel insights into intra-islet regulatory pathways in the
      modulation of glucagon secretion and provide potential opportunities to develop
      therapeutic approaches for the correction of alpha-cell dysfunction in diabetes.

PMID- 21099285
TI  - GLP-1 protects beta-cells against apoptosis by enhancing the activity of an IGF
      2/IGF1-receptor autocrine loop.
AB  - GLP-1 protects beta-cells against apoptosis by still incompletely understood
      mechanisms. In a recent study, we searched for novel anti-apoptotic pathways by
      performing comparative transcriptomic analysis of islets from Gipr-/-;Glp-1r-/-
      mice, which show increased susceptibility to cytokine-induced apoptosis. We
      observed a strong reduction in IGF-1R expression in the knockout islets
      suggesting a link between the gluco-incretin and IGF-1R signaling pathways. Using
      MIN6 and primary islet cells, we demonstrated that GLP-1 strongly stimulates IGF
      1R expression and that activation of the IGF-1R/Akt signaling pathway required
      active secretion of IGF-2 by the beta-cells. We showed that inactivation of the
      IGF-1 receptor gene in beta-cells or preventing its up-regulation by GLP-1, as
      well as suppressing IGF-2 expression or action, blocked the protective effect of
      GLP-1 against cytokine-induced apoptosis. Thus, an IGF-2/IGF-1 receptor autocrine
      loop operates in beta-cells and GLP-1 increases its activity by enhancing IGF-1R
      expression and by stimulating IGF-2 secretion. This mechanism is required for GLP
      1 to protect beta-cells against apoptosis.

PMID- 21099286
TI  - MiR-30 family and EMT in human fetal pancreatic islets.
AB  - Small, non-coding ribonucleotides called micro RNAs (miRNAs) have recently
      emerged as important regulators of cell function. MiRNAs regulate gene expression
      mainly by binding to the 3' UTR of mRNAs and thereby inhibit the translation of
      target mRNAs. The abundance of many miRNAs is altered under physiological and
      pathophysiological conditions, such as cancer and neurodegeneration. Recent data
      suggest that miRNAs also have an important role in regulation of insulin gene
      transcription, insulin secretion, and pancreatic islet cell function. An
      interesting study by Joglekar et al. published in this issue of ISLETS suggests
      that the miR-30 family of miRNAs may control the epithelial-to-mesenchymal
      transition of primary cultures of human pancreatic epithelial cells by negatively
      regulating the translation of mesenchymal gene transcripts such as vimentin.
      These findings are in agreement with previous data that suggest an important role
      for one of the miR-30 family members (miR-30d) in insulin gene expression in
      pancreatic beta cells. In summary, the report by Joglekar et al provides a
      significant advancement in understanding the role of miRNAs in pancreatic islet
      development and suggests that manipulation of miR-30 family of miRNA expression
      may provide an important means to generate and expand pancreatic beta cells from
      human fetal pancreatic progenitors.

PMID- 21099287
TI  - Stress hypERactivation in the beta-cell.
AB  - In pancreatic beta-cells, the endoplasmic reticulum (ER) is the crucial site for
      insulin biosynthesis, as this is where the protein-folding machinery for
      secretory proteins is localized. Perturbations to ER function of the beta-cell,
      such as a high demand for insulin secretion, can lead to an imbalance in protein
      homeostasis and lead to ER stress. This stress can be mitigated by an adaptive,
      cellular response, the unfolded protein response (UPR). UPR activation is vital
      to the survival of beta-cells, as these cells represent one of the most
      susceptible tissues for ER stress, due to their highly secretory function.
      However, in some cases, this response is not sufficient to relieve stress,
      leading to apoptosis and contributing to the pathogenesis of diabetes. Recent
      evidence shows that ER stress plays a significant role in both type 1 and type 2
      diabetes. In this review, we outline the mechanisms of ER stress-mediated beta
      cell death and focus on the role of ER stress in various forms of diabetes,
      particularly a genetic form of diabetes called Wolfram syndrome.

PMID- 21099288
TI  - Kinetics of insulin secretion to acute, repetitive stimulation of islets in vivo
      in Sprague Dawley rats.
AB  - The exhaustibility of in vivo insulin secretion under repeated stimulations was
      investigated in male Sprague Dawley rats. Eight pulses of either 300 mg/kg
      glucose (G), or 300 mg/kg glucose plus 0.25 mg/kg forskolin (G+F) were
      administered for each rat at every 30 min for 4 hours through the jugular vein.
      Forskolin is a chemical that potentiates glucose-stimulated insulin release by
      raising intracellular cAMP levels. After each infusion, blood samples from the
      hepatic portal vein were collected at 2, 5, 10, 15 and 29 min and glucose,
      insulin and C-peptide levels were measured. Analyses of our results indicate
      that: (1) the addition of forskolin led to increased insulin release as judged by
      peak insulin secretion values and by incremental insulin release for both first
      and second phases; (2) despite the enhanced insulin release, the G+F protocol did
      not increase glucose disposal more than the G protocol alone, as judged by the
      maximum and minimum glucose levels that the system could attain in each cycle;
      and most importantly, (3) insulin secretion from beta-cells was not exhausted,
      even after 8 repeated half-hourly stimulations with either G or G+F. We believe
      that this is the first study to investigate in vivo beta-cell exhaustion by
      repeated stimulation in an animal model and our data show that in an acute
      setting, islets are capable of robust insulin secretion. The extension of this
      study to investigate insulin secretion in pre-diabetic states may be informative
      of the early pathogenic mechanisms.

PMID- 21099289
TI  - XIAP inhibition of beta-cell apoptosis reduces the number of islets required to
      restore euglycemia in a syngeneic islet transplantation model.
AB  - Clinical pancreatic islet transplantation has great promise as a treatment for
      type 1 diabetes but despite recent advances, it is still limited by the need for
      lifelong immunosuppression, restricted availability of donor islets, and
      uncertainty regarding long-term graft survival. Using a syngeneic, suboptimal
      islet transplantation model, we asked whether adenoviral overexpression of an
      anti-apoptotic protein, the X-linked inhibitor of apoptosis protein (XIAP) would
      protect transplanted islet cells from death and reduce the number of islets
      required for successful transplantation. Transplantation of 100 XIAP-expressing
      islets into the kidney capsule of syngeneic Balb/c mice restored euglycemia in
      86% of recipients, where transplantation of 100 islets transduced with a control
      adenovirus expressing LacZ restored euglycemia in only 27% of recipients.
      Analysis of islet grafts by insulin/TUNEL double immunostaining revealed fewer
      apoptotic beta-cells in recipients of XIAP- compared with LacZ-expressing grafts
      (0.8+/-0.5 vs. 2.4+/-0.8 double-positive cells/graft), suggesting that XIAP
      enhances graft success by inhibiting beta-cell apoptosis in the immediate post
      transplant period. In summary, XIAP overexpression inhibits beta cell apoptosis
      in syngeneic islet transplants, thereby reducing the number of islets and
      decreasing the number of days required to restore euglycemia. These data raise
      the possibility that ex vivo XIAP gene transfer in islets prior to
      transplantation has the potential to increase the number of donor islets
      available for transplantation and may enhance graft function and long-term
      transplant success.

PMID- 21099290
TI  - Immunocytochemical localization of cleaved caspase-3 in pancreatic islets from
      type 1 diabetic subjects.
AB  - AIMS/ HYPOTHESIS: Caspase-3 is a main effector caspase of the apoptotic cascade.
      Involvement of caspase-3 has been implicated in a beta cell cloned cell line from
      type 1 diabetic subjects and in isolated islets from type 2 diabetic subjects.
      RESULTS: The control islets revealed cleaved caspase-3 positive cells in about
      4.7 % in the total islet cells with large and small islets positive at 4.1 % and
      6.8%, respectively. The islets from type 1 diabetic patients showed higher
      immunopositive cells at 16 % in the total islets with large and small islets
      positive at 14% and 17%, respectively, 3.4, 3.6 and 2.4 times that of the
      corresponding control values. METHODS: Using commercially available rabbit anti
      cleaved caspase-3 antibody, immunocytochemical staining was performed on 8 cases
      of pancreatic tissues from type 1 diabetic subjects and age-matched controls
      obtained at autopsy. Islets were divided into large islets containing more than
      34 islet cells and small islets containing less than 34 islet cells. Cleaved
      caspase-3 immunostained islet cells were calculated for large and small islets,
      respectively, with total number of islet cells and total percentage of cleaved
      caspase-3 positive cells. CONCLUSION/INTERPRETATION: The islets from type 1
      diabetics were a mixture of major small-sized islets consisting of insulin-poor
      and glucagon-rich cells with more caspase-3 positive cells, and occasional large
      islets, consisting of non-insulin-cells (> 1%) but glucagon- , somatostatin- and
      PP-rich cells with normal caspase-3 positive cells. The more positive staining
      for caspase-3 in islets from type 1 diabetics may correspond to accelerated
      apoptosis cascade in the islets before processing to eventual cell death.

PMID- 21099291
TI  - Impaired insulin turnover in islets from type 2 diabetic patients.
AB  - Failure of pancreatic beta-cells contributes to the development of type 2
      diabetes. Besides evidence of reduced glucose-stimulated insulin secretion and
      beta-cell mass, little information is available about the molecular deficits of
      human diabetic islets. Islets were isolated from macroscopically normal
      pancreatic tissue from 8 patients with type 2 diabetes and 17 matched non
      diabetic patients who underwent pancreatic surgery. Insulin content and insulin
      secretion were measured before and after islet stimulation with 25 mM glucose for
      2 hours. In parallel, we also investigated the subcellular localization of
      polypyrimidine tract-binding protein 1 (PTBP1), whose nucleocytoplasmic
      translocation is involved in the rapid posttranscriptional up-regulation of
      insulin biosynthesis following islet stimulation with glucose and GLP-1. Glucose
      stimulated insulin secretion was decreased, albeit not significantly, in type 2
      diabetic islets compared to non-diabetic islets. Stimulation increased the total
      amount of insulin (islet insulin content + secreted insulin) in islet preparation
      from non-diabetic patients, but not from type 2 diabetic subjects. Furthermore,
      the nuclear levels of PTBP1 were decreased in stimulated non-diabetic islets, but
      not in type 2 diabetic islets. These results suggest that impairment of rapid
      insulin increase in response to glucose is a specific trait of type 2 diabetic
      islets. Nuclear retention of PTBP1 is likely to play a role in this deficit,
      which in turn can contribute to impaired insulin secretion in type 2 diabetes.
      Overall, these data highlight the importance of investigating mechanisms of
      insulin biosynthesis and degradation to gain insight into the pathogenesis of
      type 2 diabetes.

PMID- 21099292
TI  - c-Myc directly induces both impaired insulin secretion and loss of beta-cell
      mass, independently of hyperglycemia in vivo.
AB  - c-Myc (Myc) is a mediator of glucotoxicity but could also independently
      compromise beta-cell survival and function. We have shown that after Myc
      activation in adult beta-cells in vivo, apoptosis is preceded by hyperglycemia,
      suggesting glucotoxicity might contribute to Myc-induced apoptosis. To address
      this question conditional Myc was activated in beta-cells of adult pIns-c
      MycER(TAM) mice in vivo in the presence or absence of various glucose-lowering
      treatments, including exogenous insulin and prior to transplantation with wild
      type islets. Changes in blood glucose levels were subsequently correlated with
      changes in beta-cell mass and markers of function/differentiation. Activation of
      c-Myc resulted in reduced insulin secretion, hyperglycemia and loss of beta-cell
      differentiation, followed by reduction in mass. Glucose-lowering interventions
      did not prevent loss of beta-cells. Therefore, Myc can cause diabetes by direct
      effects on beta-cell apoptosis even in the absence of potentially confounding
      secondary hyperglycemia. Moreover, as loss of beta-cell differentiation/function
      and hyperglycemia are not prevented by preventing beta-cell apoptosis, we
      conclude that Myc might contribute to the pathogenesis of diabetes by directly
      coupling cell cycle entry and beta-cell failure through two distinct pathways.

PMID- 21099293
TI  - Oct-1 functions as a sensor for metabolic and stress signals.
AB  - Oct-1 is a member of the POU domain transcription factor family. The protein in
      this family typically contains a bipartite DNA binding domain, in which two sub
      domains, covalently connected by a flexible linker, normally recognize DNA
      through major groove interaction on the opposite sides of the helix. The
      classical recognition sequence is known as the octamer motif "ATGCWAAT", where W
      can be either "A" or "T". This ubiquitously expressed transcription factor exerts
      multiple biological functions via up or downregulating the expression of a large
      profile of target genes in different cell lineages, including those in pancreatic
      islets. Apparently, it is essential for embryonic development as Oct-1-deficient
      embryos die during gestation. Recent studies from our group and others revealed
      that Oct-1 serves as a sensor for both metabolic as well as stress/survival
      signals.

PMID- 21099294
TI  - Think zinc: New roles for zinc in the control of insulin secretion.
AB  - Genome wide association studies have identified the islet-restricted zinc
      transporter ZnT8 (SLC30A8) as a likely player in the control of insulin secretion
      and the risk of developing type 2 diabetes. The author's laboratory and others
      have now developed knockout mouse models for the ZnT8 gene, and have studied the
      impact of the at-risk R325W polymorphism on the activity of this crucial islet
      zinc transporter. Whilst there are intriguing differences between the phenotypes
      of the animal models the new studies provide strong evidence that the
      polymorphism in the SLC30A8 gene identified by human genetic screens is causal
      for the increased disease risk. The new results also reinforce the view that this
      transporter represents an exciting therapeutic target for intervention in type 2
      diabetes.

PMID- 21099295
TI  - The CDK4-pRB-E2F1 pathway : A new modulator of insulin secretion.
AB  - Pancreatic beta-cells are sensors of circulating glucose levels that control
      insulin secretion through a finely-tuned process. Under hyperglycemic conditions,
      glucose enters the cell, generates ATP, leading to a subsequent closure of
      voltage-dependent ATP channels, membrane depolarization, Ca2(+) entry and
      exocytosis of insulin vesicles. In pathological conditions, such as during type 2
      diabetes (T2D), chronic hyperglycemia will ultimately result in decreased
      capability of beta-cells to secrete sufficient amount of insulin to regulate
      glycemia. Therefore, understanding of the mechanisms of modulation of insulin
      secretion could be of interest for the treatment of diabetes. We have
      demonstrated that a particular cell cycle regulator, E2F1, is involved in
      pancreatic post-natal growth through its functions in the control of beta-cell
      proliferation. Based on the observation that cell cycle regulators were highly
      expressed in non-proliferating beta-cell, we hypothesized that these proteins
      could also have a direct role in pancreatic beta-cell function. Altogether our
      data unravel a new function for these factors in the control of insulin secretion
      and open up new avenues for the treatment of diabetes.

PMID- 21099296
TI  - The NALCN ion channel is a new actor in pancreatic beta-cell physiology.
AB  - Ion channels are critical components of cell excitability involved in many
      physiological processes, including hormone secretion, and are thought be targets
      of choice in a pathological context. In the present paper, we summarize and
      discuss our recent findings on a four domain cation channel named NALCN which has
      been previously described as mediating a TTX-resistant leak sodium current in
      neurons. We recently reported that NALCN is also expressed in rodent islets of
      Langerhans as well as in the mouse MIN6 pancreatic beta-cell line. This
      pancreatic NALCN channel encodes for a cation current triggered by acetylcholine
      activation of M3 muscarinic receptors. Importantly, the activation mechanism is
      independent of G protein action, but is dependent on a SFK-pathway, and involves
      the co-inclusion of M3 muscarinic receptors and NALCN in the same complex.
      Although additional work is now needed, considering the importance of the
      cholinergic control on the pancreatic beta-cell function, this study has
      unravelled the molecular identity of a new actor in pancreatic beta-cell
      excitability that could be a major target for new compounds modulating insulin
      secretion.

PMID- 21099297
TI  - Electrical activity in pancreatic islet cells: The VRAC hypothesis.
AB  - A major aspect of stimulation of beta-cell function by glucose is the induction
      of electrical activity. The ionic events that underlie beta-cell electrical
      activity are understood in some detail. At sub-stimulatory glucose
      concentrations, the beta-cell is electrically 'silent'. Increasing the glucose
      concentration to stimulatory levels results in a gradual depolarisation of the
      membrane potential to a threshold potential where 'spikes' or action potentials
      are generated. These action potentials represent the gating of voltage-sensitive
      Ca2(+) channels, leading to Ca2(+) entry into the cell, thus triggering the
      release of insulin. The stimulatory actions of glucose on the beta-cell depend on
      the metabolism of the hexose. A major question concerns the molecular
      mechanism(s) whereby beta-cell plasma membrane potential is regulated by changes
      in glucose metabolism in the cell. This article provides a brief summary of the
      evidence suggesting that, in addition to metabolically-regulated K(ATP) channels,
      beta-cells are equipped with a volume-regulated anion channel that is activated
      by glucose concentrations within the range effective in modulating electrical
      activity and insulin release.

PMID- 21099298
TI  - Intracranial ectopic pancreatic tissue.
AB  - In 2007 a young Japanese female was reported to suffer from a congenital brain
      malformation with a non-functioning pancreatic endocrine tumor arising from
      intracranial ectopic pancreatic tissue. Ectopic pancreas is normally confined to
      other endodermally-derived organs and not previously reported to be found in the
      brain. Therefore, we sought to better understand the true pancreatic nature of
      the tissue and to further understand the mechanism by which ectopic pancreas
      could appear in the brain. A detailed immunohistochemical analysis for pancreatic
      hormones, transcription factors, ductal/exocrine markers and stem cell markers on
      sections from the resected tumor tissue was performed. All five endocrine cell
      types are observed but pancreatic polypeptide cells are quite rare and ghrelin
      and glucagon cells are more numerous than in normal human pancreas. Insulin
      immunoreactive cells stain for c-peptide. The beta-cell specific transcription
      factor, Nkx6.1, is expressed only in the insulin immunoreactive cells while
      neither Ptf1a or PDX-1 immunoreactive cells can be observed. Duct-like structures
      stain strongly for pan-cytokeratin and E-cahderin. The exocrine like tissue
      stains strongly for pancreatic amylase, lipase and chymotrypsin. Ngn-3 cells were
      very rare and not in the pancreatic area. Examining for endodermal markers we
      observed Sox17 had a weak staining in some areas of the pancreatic tissue but was
      much less widely expressed than FoxA2. The tumor tissue did not stain for the
      stem cell markers, Oct-4 and Sox2. It is speculated that the ectopic pancreas
      domain may arise from misexpression of homeodomain transcription factors related
      to Pdx1 within a domain of Ptf1a expression.

PMID- 21099299
TI  - Cleaved caspase-3 immunocytochemical staining for pancreatic islets and
      pancreatic endocrine tumors: A potential marker for biological malignancy.
AB  - AIMS: Involvement of caspase (C)-3 has been implicated in beta-cells from
      diabetic subjects. This study is aimed to immunocytochemically identify cleaved
      caspase-3 (CC-3) positive cells in pancreatic endocrine tumors (PETs) compared
      with control islets. RESULTS: Control islets revealed some CC-3 positive cells,
      ranging from 3.6 to 7.3% of total islet cells. Small islets in the pseudocapsule
      of PETs showed higher immunopositive cells at about 9% for CC -3, suggesting an
      accelerated apoptosis in these compressed, elongated islets before proceeding to
      imminent cell death. Majority of primary PETs except 9 cases were negative for CC
      -3 immunostaining: five insulinomas, one somatostatinoma, one gastrinoma and one
      pancreatic peptidoma (PPoma) were positive for CC -3. METHODS: Using commercially
      available rabbit anti-CC-3, immunocytochemical staining was performed in 42 cases
      of PETs compared with control islets. CONCLUSIONS/INTERPRETATION: Majority of
      primary PETs (28/37, 76%) were negative for CC-3, suggesting that majority of
      PETs are not on apoptotic program of the normal islets. Since 21 of 24 (88%) of
      potentially malignant primary non-beta-cell PETs were negative, whereas 5 of 12
      (42%) benign insulinomas were positive for CC-3 immunostaining, CC-3 negative
      immunostaining may serve as a possible malignant marker for all PETs.

PMID- 21099300
TI  - Identification of genes selectively disallowed in the pancreatic islet.
AB  - We have previously identified two genes, encoding lactate dehydrogenase (Ldha)
      and the monocarboxylate carrier, MCT1 (Slc16a1) whose expression is remarkably
      low in pancreatic beta-cells and islets. We sought here to determine whether
      these may be part of a larger family of genes selectively repressed
      ("disallowed") in the pancreatic islet. Using new and publicly available
      microarray data, we undertook a bioinformatic analysis of gene expression in
      islets and a range of other murine tissues. We compared data sets from three
      sources of mouse pancreatic islets with a total of 30 datasets from nine tissues,
      to identify genes with at least five-fold down-regulation in islets. 39 genes
      were revealed as being specifically repressed in islets. These included Ldha and
      Slc16a1 as expected but also genes involved in several other metabolic pathways
      which could affect glucose stimulated insulin secretion. Of these, adenylate
      kinase 3 (AK3) is a mitochondrial enzyme which acts on GTP, and ornithine
      aminotransferase (OAT) lies on the pathway converting glutamate to ornithine. The
      removal of an enzyme which could dissipate mitochondrial GTP levels in beta cells
      provides support for the theory that mitochondrial GTP may be an important for
      regulating insulin secretion, whilst blocking an alternative metabolic fate for
      glutamate is consistent with a signalling role for glutamate. The identification
      of these genes should inform efforts to generate fully functional beta-cells from
      stem cell sources, and may provide new targets in type 2 diabetes.

PMID- 21099301
TI  - The thyroid hormone T3 improves function and survival of rat pancreatic islets
      during in vitro culture.
AB  - Ex vivo islet cell culture in the presence of stimulating factors prior to
      transplantation is considered a good strategy in contrast to the short conclusion
      of islets transplantation. Previously, we demonstrated how T3 can increase b-cell
      function via specific activation of Akt; therefore we hypothesized that thyroid
      hormone T3 can be considered a promising candidate for the in vitro expansion of
      islet cell mass. Rat pancreatic islets have been isolated by the collagenase
      digestion and cultured in the presence or not of the thyroid hormone T3 10-7 M.
      Islets viability has been evaluated by the use of two different dyes, one cell
      permeable green fluorescent dye and propidium iodide, and by the analysis of core
      cell damage upcoming. Moreover, islets function has been evaluated by insulin
      secretion. The ability of b-cells to counteract apoptosis induced by
      streptozotocin has been analyzed by TUNEL assay. We demonstrated that treatment
      of primary cultures of rat pancreatic islets with T3 results in augmented beta
      cell vitality with an increase of their functional properties. In addition, a
      sensible reduction of the core cell damage has been observed in the T3 treated
      islets, suggesting the preservation of the beta-cells integrity during the
      culture period. Nonetheless, the insulin secretion is sensibly augmented after T3
      stimulation. The strong increment shown in Akt activation suggests the
      involvement of this pathway in the observed phenomena. In conclusion we indicate
      T3 as a good factor to improve ex vivo islets cell culture.

PMID- 21099302
TI  - Role of the TLR signaling molecule TRIF in beta-cell function and glucose
      homeostasis.
AB  - Type 2 diabetes is a metabolic and inflammatory disease characterized by
      deteriorating islet function and increased levels of inflammatory cytokines. The
      inflammatory milieu induced in type 2 diabetes exacerbates islet dysfunction and
      insulin resistance, and therapies that target inflammation can improve glycemic
      control in patients with type 2 diabetes. Inflammation in type 2 diabetes may be
      the result of the stimulation of Toll-like receptors (TLRs), one of the many
      mediators of inflammation. TLRs can be activated by both exogenous and endogenous
      ligands, and are responsible for activating NFkappaB and interferon- inducible
      inflammatory gene expression. We examined the role of the TIR-domain containing
      adaptor-inducing interferon-beta (TRIF or TICAM-1), a major signaling molecule
      for TLR3 and TLR4, in b-cell function and glucose homeostasis by examining mice
      lacking TRIF (Trif-(/)-), TLR3 (Tlr3-(/)-) or TLR4 (Tlr4-(/)-). Male, 10-week old
      Trif-(/)- mice exhibit a moderate but significant increase in fasting blood
      glucose compared to C57BL/6 controls (12.0 +/- 0.9 vs. 9.7 +/- 0.4 mM; p < 0.05)
      as well as impaired glucose tolerance revealed by IPGTT (AUC: 2850 +/- 236 vs.
      2050 +/- 108; p < 0.005) whereas Tlr3-(/)- and Tlr4-(/)- mice have normal glucose
      tolerance. Interestingly, Trif-(/)- mice have normal insulin sensitivity yet have
      increased plasma insulin levels (180 +/- 22 vs. 89 +/- 24 pM; p < 0.05). Islets
      isolated from Trif-(/)- mice have impaired glucose-stimulated insulin secretion,
      with a diminished first-phase insulin response to glucose. Immunohistological
      analysis revealed that age-matched Trif-(/)- and control mice have normal islet
      morphology, although Trif-(/)- mice have increased b-cell mass (3.5 +/- 0.9 vs.
      1.7 +/- 0.2 mg; p < 0.05). In summary, mice lacking TRIF have hyperglycemia
      associated with b-cell dysfunction that may be partly compensated for by
      increased b-cell mass. These studies suggest a role for TLR signaling in glucose
      homeostasis, and raise the possibility that TRIF signaling is required for normal
      b-cell function.

PMID- 21099303
TI  - Islet neogenesis from the constitutively nestin expressing human umbilical cord
      matrix derived mesenchymal stem cells.
AB  - The scarcity of islets for transplantation calls for an alternative sources of
      islets. The human umbilical cord has been shown to be a reservoir of multipotent
      stem cells with capacity to differentiate into ectodermal, mesodermal and
      endodermal lineages. The present investigation deals with isolation and
      characterization of mesenchymal stem sells (MSC) derived from human umbilical
      cord and their differentiation into functional islets. Since these MSCs were
      found to constitutively express nestin we hypothesized that these would be ideal
      candidates for islet neogenesis without any further manipulation. Human umbilical
      cord matrix stem cells (hUCMSCs) were found to express CD29, CD44, CD73, CD90,
      CD105, smooth muscle actin, nestin, vimentin, proliferation marker Ki67 and
      embryonic markers Oct4, SSEA4. These were found to be negative for CD33, CD34,
      CD45 and HLA DR. Human UCMSCs exhibited high proliferating capacity for extended
      period indicating potential for scaling up. When subjected to a cocktail of
      specific differentiating factors, these cells differentiated into fat, cartilage,
      bone, neurons and islet like clusters (ILCs). These ILCs stained positive for
      diphenylthiocarbazone (DTZ) and expressed human C-peptide, insulin and glucagon.
      Real time qPCR analysis of newly generated islets further demonstrated abundance
      of Pdx-1, Ngn3, insulin, glucagon and somatostatin transcripts. On
      transplantation in experimental diabetic mice these ILCs restored normoglycemia,
      body weight and exhibited normal glucose tolerance test indicating their
      functional status. Thus, the present study demonstrates potential of
      constitutively expressing nestin positive progenitor from umbilical cord as a
      novel source for islet neogenesis and their usage in cell replacement therapy for
      diabetes.

PMID- 21099304
TI  - The role of Islet-1 in the endocrine pancreas: Lessons from pancreas specific
      Islet-1 deficient mice.
AB  - Recently, we have reported the LIM-homeodoman (HD) transcriptional regulator,
      Islet-1 (Isl-1) as a key regulator for pancreatic islets after the secondary
      transition and into early postnatal stages in mice. Previously, the role of Isl-1
      had only been examined during early pancreas development in vivo and cell lines.
      These early studies concluded that Isl-1 is required for the differentiation of
      early endocrine cells, and hormone gene expression is regulated by Isl-1 in cell
      culture. However, it was not clear from these studies whether the regulation of
      hormone gene transcription by Isl-1 was a direct transcriptional event. In
      addition, the function of Isl-1 during the formation of principle hormone
      producing endocrine cells had not been investigated since Isl-1 null animals die
      prior to the formation of these cells. Using pancreas-specific inactivation of
      Isl-1 in mice, we have elucidated the role of Isl-1 during maturation,
      proliferation and survival of the endocrine pancreas after the secondary
      transition. We have also identified MafA, a potent Insulin gene regulator, as the
      first direct target of Isl-1 in beta-cells.

PMID- 21099305
TI  - In vivo functional heterogeneity among beta-cells.
AB  - The concept of functional heterogeneity among beta-cells proposes that each cell
      differs in its sensitivity to glucose and is recruited in a glucose-dependent
      manner into both biosynthetic and secretory active states in order to adapt
      insulin secretion to the metabolic environment. Therefore, characterization of
      beta-cell populations with different metabolic sensitivities would lead to the
      development of new therapeutic strategies. Based on heterogeneous surface PSA
      NCAM expression on beta-cells, we have recently characterized two groups of
      cells, namely beta(high) and beta(low)-cells, in rat. Differences in insulin
      secretory capacity and in gene expression profiles suggest that beta(low)-cells
      are immature and/or non-functional cells in contrast to highly glucose responsive
      fully functional beta(high)-cells. Moreover, the relative distribution of
      beta(high) and beta(low)-cells correlated with physiological and pathological
      states regarding the functional beta-cell mass. Here we summarize our main
      results on beta(high) and beta(low)-cell populations and discuss some of the open
      remaining questions.

PMID- 21099306
TI  - Targeting triglyceride/fatty acid cycling in beta-cells as a therapy for
      augmenting glucose-stimulated insulin secretion.
AB  - Insulin secretion from pancreatic beta-cells is triggered by signals arising from
      the metabolism of glucose and acting through separate initiation and
      amplification pathways. Despite decades of investigation, crucial details of this
      mechanism remain poorly understood, especially those relating to the amplifying
      pathway(s). Advances in this area are vital if we are to understand why insulin
      secretion fails in type 2 diabetes and to develop strategies to overcome this
      failure. Indeed, targeting the amplifying pathway(s) would constitute an
      attractive therapy for augmenting insulin secretion because it would closely link
      secretory responsiveness to the prevailing glycaemia. It is therefore noteworthy
      that the possibility of augmenting the amplification pathway(s) has recently been
      highlighted by studies investigating a metabolic cycle that links the breakdown
      of triacylglycerol (TAG), release of fatty acid (FA), and subsequent re
      incorporation of that FA into TAG. This work reinvigorates and extends the long
      standing idea that partitioning of endogenous lipid metabolism towards
      esterification products promotes the amplification phase of the secretory
      response. These conceptual advances, and their possible therapeutic application,
      will be discussed in the following article.

PMID- 21099307
TI  - B cell therapy is beta-tested: Rituximab puts a pause on beta-cell destruction.

PMID- 21099308
TI  - Partial dorsal agenesis accompanied with circumportal pancreas in a donor for
      islet transplantation.
AB  - As embryonic development of the pancreas progresses, a wide range of congenital
      anomalies and variations can occur. We report on the incidental observation of
      partial agenesis of the dorsal pancreas coexistent with cricumportal pancreas in
      a donor for islet transplantation. We successfully recovered a high yield of
      islets from such a pancreas, and the islet recipient achieved insulin
      independence after transplant. This case report discusses the suitability of the
      anomalous pancreas as a donor organ for islet transplant and the possible
      embryologic association between the two entities.

PMID- 21099309
TI  - Activation of the AMP-activated protein kinase enhances glucose-stimulated
      insulin secretion in mouse beta-cells.
AB  - The AMP-activated protein kinase (AMPK) is one of the key players in cellular
      energy regulation adapting cellular demands to nutritional and metabolic
      variations. Oral antidiabetic drugs like metformin and glitazones
      (thiazolidinediones) are known to stimulate this enzyme. Besides their
      established action on peripheral organs including liver and muscles, it has been
      claimed that these drugs may affect beta-cell function. However, it is still a
      matter of debate whether pharmacological AMPK stimulation increases or decreases
      insulin secretion. To study this point and to reveal mechanisms underlying
      changes in insulin secretion we used the specific AMPK activator AICAR and
      investigated its effects on stimulus-secretion coupling. Membrane potential and
      currents were measured by the patch-clamp technique, [Ca (2+)]c, mitochondrial
      membrane potential, and NAD(P)H by fluorescence techniques and insulin secretion
      by a radioimmunoassay. AICAR enhanced glucose-stimulated insulin release, an
      effect that can be attributed to the augmentation of electrical activity and [Ca
      (2+)]c resulting from an AICAR-evoked inhibition of the KATP current. This latter
      effect was not due to a direct interaction of AICAR with the K[ATP] channels but
      was dependent on cell metabolism. AICAR did not affect mitochondrial membrane
      potential or NAD(P)H autofluorescence. Metformin mimicked the action of AICAR on
      electrical activity, [Ca (2+) ]c, and K[ATP] current. However, compared to AICAR
      the effects were less pronounced and not sufficient to stimulate insulin
      secretion. In conclusion, activation of AMPK augments nutrient-induced insulin
      secretion. Thus, targeting AMPK of beta-cells may be an appropriate strategy for
      the treatment of disturbed glucose homeostasis..

PMID- 21099310
TI  - Isolated human islets contain a distinct population of mesenchymal stem cells.
AB  - Islet replacement is a promising approach for type-1 diabetes treatment, but the
      shortage of organ donors demands new sources of beta-cells. The use of
      stem/precursor cells may represent an attractive alternative. Islet-derived
      stem/precursor cells (hIPC) have been isolated from human islet preparations, but
      neither their origin, nor their contribution to beta-cell formation in the adult
      pancreas, are well understood. To study these cells in more detail hIPC were
      isolated from purified human islets, cultured and functionally characterized.
      Cultured hIPC did not express the genes for endocrine hormones. These cells
      exhibited the capacity to aggregate and form clusters when transferred to serum
      free medium. In these clusters the expression of insulin, glucagon, and
      somatostatin genes is induced. Human IPC lack expression of Von Willebrand
      Factor, CD31, CD34, CD45, and CK19 and CA19.9, demonstrating that hIPC are
      neither of hematopoietic, endothelial, nor of ductal origin. The mesenchymal stem
      cells (MSC) markers CD105, CD90, CD73, CD44, CD29, and CD13 are expressed, as
      well as nestin and vimentin. With the appropriate stimuli the cells can
      differentiate into adipocytes and osteoblasts lineages. Also hIPC express the
      pericyte markers CD146, NG2, alphaSMA and PDGF-Rbeta. Immunoflowcytometry
      revealed that human islets contain 2.0 +/- 0.8% of CD105/CD90 double-positive
      cells. Confocal microscopy showed that these cells reside within the human
      islets. Altogether our data revealed the presence of a distinct MSC-like stem
      cell population in isolated human islets.

PMID- 21099311
TI  - Expression of fatty acid binding proteins 3 and 5 genes in rat pancreatic islets
      and INS-1E cells: regulation by fatty acids and glucose.
AB  - Fatty acids binding proteins (FABPs) are involved in uptake, binding, transport
      and metabolism of fatty acids (FAs). Although FAs are known to stimulate insulin
      secretion from pancreatic islets when transiently elevated, while contributing to
      islet loss of function, lipotoxicity and apoptosis when chronically elevated,
      almost nothing is known regarding the FABPs in this tissue. The present study
      aimed at exploring the expression pattern and regulation of FABPs in rat islets
      and the insulin-secreting INS-1E cells. Rat islets and INS-1E cells expressed the
      heart/muscle type (FABP3) and the epidermal type (FABP5) genes. Different FAs
      significantly enhanced the expression of both FABPs. High glucose concentration
      induced a similar elevation of both FABP mRNA levels, and similarly to its effect
      on insulin 1 mRNA. Addition of oleic or palmitic acids to glucose did not render
      a further effect. FABP3 gene expression increased in response to PPARalpha
      agonist, while FABP5 increased in response to PPARalpha and PPARgamma agonists,
      and decreased in response to a PPARbeta agonist. Beta-oxidation of FAs is
      required for the gene expression of both FABP genes in INS-1E cells. Inhibition
      of CPT-1 by etomoxir inhibited the oleic acid-induced FABP 3 and 5 gene
      expression, while activation of AMPK by metformin amplified the oleic-induced
      expression of both FABPs. FABP3 and 5 gene transcription required de novo protein
      synthesis, since inhibition by cycloheximide significantly decreased both FABP
      mRNAs. These data show a complex interrelationship between glucose and FAs in the
      control of FABP gene expression and that FABP3 and 5 may play a role in insulin
      secretion.

PMID- 21099312
TI  - alpha 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated
      apoptosis in pancreatic beta-cells.
AB  - alpha1-antitrypsin (AAT) is a serine protease inhibitor, which recently has been
      shown to prevent type 1 diabetes (T1D) development, to prolong islet allograft
      survival and to inhibit beta-cell apoptosis in vivo. It has also been reported
      that T1D patients have significantly lower plasma concentrations of AAT
      suggesting the potential role of AAT in the pathogenesis of T1D. We have
      investigated whether plasma-purified AAT can affect beta-cell function in vitro.
      INS-1E cells or primary rat pancreatic islets were used to study the effect of
      AAT on insulin secretion after glucose, glucagon-like peptide-1 (GLP-1) and
      forskolin stimulation and on cytokine-mediated apoptosis. The secreted insulin
      and total cyclic AMP (cAMP) were determined using radioimmunoassay and apoptosis
      was evaluated by propidium iodide staining followed by FACS analysis. We found
      that AAT increases insulin secretion in a glucose-dependent manner, potentiates
      the effect of GLP-1 and forskolin and neutralizes the inhibitory effect of
      clonidine on insulin secretion. The effect of AAT on insulin secretion was
      accompanied by an increase in cAMP levels. In addition, AAT protected INS-1E
      cells from cytokine-induced apoptosis. Our findings show that AAT stimulates
      insulin secretion and protects beta-cells against cytokine-induced apoptosis, and
      these effects of AAT seem to be mediated through the cAMP pathway. In view of
      these novel findings we suggest that AAT may represent a novel anti-inflammatory
      compound to protect beta-cells under the immunological attack in T1D but also
      therapeutic strategy to potentiate insulin secretion in type 2 diabetes (T2D).

PMID- 21099313
TI  - Is Lipotoxicity presents in the early stages of an experimental model of
      autoimmune diabetes? Further studies in the multiple low dose of streptozotocin
      model.
AB  - An increased availability of plasma free fatty acids (FFA) seems to play a role
      in the early stages of experimental type 1 diabetes mellitus induced in C57BL/6J
      mice by multiple low doses of streptozotoxin (mld-STZ). We analyzed the temporal
      changes of: (1) plasma and skeletal muscle lipids and their relationship with
      glucose metabolism; (2) triglyceride (Tg) concentration in isolated islets; (3)
      intraperitoneal glucose tolerance test; and (4) insulin secretion patterns when
      the three mutually interactive glucose signaling pathways were activated. Animals
      were killed by cervical dislocation at days 4, 6, 7, 8, 9 and 12 post first
      injection of mld-STZ. Compared with control mice, we observed: (1) at day 6, a
      significant increase of plasma FFA and both muscle and islet Tg content and a
      significant decrease of muscle pyruvate dehydrogenase activity. These parameters
      further deteriorated with time. (2) plasma Tg, glucose and insulin levels and
      glucose tolerance test were significantly different only after day 8. (3) an
      increase in both phases of the glucose plus palmitate-stimulated insulin
      secretion was observed at day 4. This effect progressively decreased since day 7
      up to day 9. Moreover, an inhibitory action of cerulenin over glucose plus
      palmitate-stimulated insulin secretion was observed between days 6 and 9. Taken
      together these results suggest that early alteration in carbohydrate and lipid
      metabolism could represent a "metabolic window" which would develop between days
      6 and 8. Afterwards, subsequent immunological alterations, apoptosis and necrosis
      induced the destruction of beta cells and would mask the results mentioned above.

PMID- 21099315
TI  - An estimated 285 million people in the world have islet failure.

PMID- 21099314
TI  - Serine protease inhibitors suppress pancreatic endogenous proteases and modulate
      bacterial neutral proteases.
AB  - Pefabloc, Trasylol and Urinary Trypsin Inhibitor (UTI) have been reported to be
      effective serine protease inhibitors that impair pancreatic endogenous proteases
      resulting in improved islet yield. Here we evaluated the effect of these
      inhibitors on endogenous proteases (trypsin, chymotrypsin and elastase),
      bacterial neutral proteases (thermolysin and neutral protease) and islet
      isolation digestion samples. Protease activity was measured using a fluorimetric
      assay and islet function was assessed by dynamic perifusion. Trypsin,
      chymotrypsin and elastase were significantly inhibited by Pefabloc and UTI.
      Trasylol showed strong inhibitory effects on trypsin and chymotrypsin but also
      decreased thermolysin activity. UTI was found to inhibit the activity of
      endogenous proteases and increase the activity of bacterial neutral proteases.
      Human islets exposed to Pefabloc had reduced insulin response, unlike Trasylol or
      UTI, which had no detrimental effect on insulin secretion. Although Trasylol was
      an effective inhibitor of endogenous proteases, FDA regulatory issues preclude
      its use in clinical application and thus in the isolation process. UTI has the
      greatest potential because it impairs endogenous pancreatic proteases and
      enhances digestion enzymes.

PMID- 21099317
TI  - Islets and their antioxidant defense.
AB  - Pancreatic beta-cells secrete insulin in response to changes in extracellular
      glucose concentration. Persistent hyperglycemia during diabetes exerts toxic
      effects on islets by creating redox imbalance arising from overproduction of
      reactive oxygen species (ROS). ROS accumulation disturbs the integrity and
      physiological function of cellular biomolecules impairing viability and
      functionality of cells. Susceptibility of an organ to oxidative stress (OS) is
      determined by its defense mechanism and ability to repair DNA damage caused by
      ROS. Weak defense status of islets along with its inefficiency to repair
      oxidative DNA damage as compared to other tissues renders it extraordinarily
      sensitive to OS. Realizing the vulnerability of islet cells to oxidative damage,
      several efforts to boost their defense mechanism in the form of oral
      administration of antioxidants and overexpression of genes responsible for
      antioxidant enzymes have proven successful. Recently accountability for this low
      antioxidant defense of islets have been given by correlating it with its
      metabolic evolution.

PMID- 21099316
TI  - The isolated pancreatic islet as a micro-organ and its transplantation to cure
      diabetes: celebrating the legacy of Paul Lacy.
AB  - Over the past three decades the pancreatic islet of Langerhans has taken center
      stage as an endocrine micro-organ whose glucoregulatory function is highly
      explicable on the basis of the increasingly well understood activities of three
      highly interactive secretory cells. Islet dysfunction underlies both type 1 and
      type 2 diabetes mellitus (DM); its protection from immune attack and gluco-and
      lipo-toxicity may prevent the development of DM; and its replacement by non
      surgical transplantation may be curative of DM. During a career marked by vision,
      focus and tenacity, Paul Lacy contributed substantially to the development of
      each of these concepts. In this review we focus on Lacy's contribution to the
      development of the concept of the islet as a micro-organ, how this foreshadowed
      our current detailed understanding of single cell function and cell-cell
      interactions and how this led to a reduced model of islet function encouraging
      islet transplantation. Next, we examine how clinical allotransplantation, first
      undertaken by Lacy, has contributed to a more complex view of the interaction of
      islet endocrine cells with its circulation and neighboring tissues, both "in
      situ" and after transplantation. Lastly, we consider recent developments in some
      alternative approaches to treatment of DM that Lacy could glimpse on the horizon
      but did not have the chance to participate in.

PMID- 21099318
TI  - Exercise at anaerobic threshold intensity and insulin secretion by isolated
      pancreatic islets of rats.
AB  - To evaluate the effect of acute exercise and exercise training at the anaerobic
      threshold (AT) intensity on aerobic conditioning and insulin secretion by
      pancreatic islets, adult male Wistar rats were submitted to the lactate minimum
      test (LMT) for AT determination. Half of the animals were submitted to swimming
      exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an
      overload equivalent to the AT. The other half was kept sedentary (sedentary). At
      the end of the experimental period, the rats were submitted to an oral glucose
      tolerance test and to another LMT. Then, the animals were sacrificed at rest or
      immediately after 20 minutes of swimming exercise at the AT intensity for
      pancreatic islets isolation. At the end of the experiment mean workload (% bw) at
      AT was higher and blood lactate concentration (mmol/L) was lower in the trained
      than in the control group. Rats trained at the AT intensity showed no alteration
      in the areas under blood glucose and insulin during OGTT test. Islet insulin
      content of trained rats was higher than in the sedentary rats while islet glucose
      uptake did not differ among the groups. The static insulin secretion in response
      to the high glucose concentration (16.7 mM) of the sedentary group at rest was
      lower than the sedentary group submitted to the acute exercise and the inverse
      was observed in relation to the trained groups. Physical training at the AT
      intensity improved the aerobic condition and altered insulin secretory pattern by
      pancreatic islets.

PMID- 21099319
TI  - FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model.
AB  - To clarify the effect of fibroblast growth factor-21 (FGF-21) on islet
      transplantation, a suboptimal number of islets were transplanted into
      streptozotocin (STZ)-induced diabetic mice with or without FGF-21 treatment.
      Three-day treatment with FGF-21 contributed to restoration of normoglycemia by
      suppressing islet graft loss. The FGF-21-treated mice showed lower glycemic
      levels despite similar insulin content in the graft than that in untreated mice
      on day 3, indicating that FGF-21 not only has a cytoprotective effect but also
      decreases beta-cell load by increasing insulin sensitivity. These results suggest
      that FGF-21 may be useful as a treatment to improve islet engraftment rates in
      clinical islet transplantation.

PMID- 21099321
TI  - Decreased senescence marker protein-30 could be a factor that contributes to the
      worsening of glucose tolerance in normal aging.
AB  - In our recent paper, we proposed that senescence marker protein-30 (SMP30) could
      be a novel molecule which was involved in an impairment of beta-cell function
      with aging. SMP30 knockout (KO) mice and wild-type (WT) mice were fed a standard
      diet (SD) or a high fat diet (HFD) for 8 weeks from 7 weeks of age. In an
      intraperitoneal glucose tolerance test at 15 weeks of age, blood glucose levels
      in SD-fed KO mice were significantly increased by 25% at 30 min after glucose
      administration compared to SD-fed WT mice. Insulin levels in SD-fed KO mice were
      significantly decreased by 37% at 30 min postglucose compared to SD-fed WT mice.
      Interestingly, an insulin tolerance test showed a greater glucose lowering effect
      in SD-fed KO mice. Morphometric analysis revealed no differences in the degree of
      HFD-induced compensatory increase in beta-cell mass and proliferation.
      Collectively, these data indicate that impairment of the early phase of insulin
      secretion underlies glucose intolerance in KO mice. Decreased SMP30 may
      contribute to the worsening of glucose tolerance that occurs in normal aging.

PMID- 21099320
TI  - No non-redundant function of suppressor of cytokine signaling 2 in insulin
      producing beta-cells.
AB  - The members of the Suppressor of Cytokine Signaling (SOCS) protein family mainly
      modulate the Janus kinase (JAK)/signal transducer and activator of transcription
      (STAT) pathway. SOCS-1 and SOCS-3 have already been shown to influence growth and
      apoptosis of pancreatic beta cells. We hypothesized that SOCS-2, which is
      expressed in pancreatic islets, also contributes to beta-cell physiology. We
      tested this hypothesis in vivo in SOCS-2-/- knockout mice and in vitro in Ins-1E
      rat insulinoma cells. We found that SOCS-2-/- mice have normal islet insulin
      secretion and unchanged glucose and insulin tolerance compared to wildtype
      controls. SOCS-2-/- are bigger than wildtype mice but body weight-corrected beta
      cell mass and islet morphology were normal. Growth hormone-induced proliferation
      of Ins-1E cells was not affected by either siRNA-mediated SOCS-2 knockdown or
      stable SOCS-2 overexpression. Interleukin-1beta mediated cell death in vitro was
      unchanged after SOCS-2 knockdown. Similarly, autoimmune destruction of beta cells
      in vivo after multiple low-dose injections of streptozotocin (STZ) was not
      altered in SOCS-2-/- mice. In summary, SOCS-2-/- knockout mice have a normal
      function of insulin-producing pancreatic beta-cells, a fully adapted beta cell
      mass and a normal morphology of the endocrine islets. Based on in vitro evidence,
      the increased beta-cell mass in the mutants is likely due to indirect adaptive
      mechanisms and not the result of altered growth hormone signaling within the beta
      cells. Immune mediated beta-cell destruction is also not affected by SOCS-2
      ablation in vitro and in vivo.

PMID- 21099322
TI  - Seeing is believing: how the MIP-luc mouse can advance the field of islet
      transplantation and beta-cell regeneration.
AB  - In the last five years, bioluminescence has emerged as a vital tool in the non
      invasive quantification of beta-cell mass following islet transplantation in
      murine models. The successes achieved in bioluminescence imaging in islet
      transplantation has prompted its use in the discipline of beta-cell regeneration.
      Employing bioluminescence permits quantifying changes in beta-cell mass in an
      individual mouse over time, which can provide valuable insights into the kinetics
      of beta-cell regeneration.

PMID- 21099323
TI  - Surgical aspects of human islet isolation.
AB  - Islet transplantation is a safe and effective procedure; however, it depends on
      the critical step of isolating high quality of islets from whole pancreas. Human
      islet isolation requires considerable experience and expertise, and is frequently
      seen as 'an art rather than a science'. However, without scientific knowledge of
      pancreatic anatomy, real experience can not be gained. In particular, an
      understanding ductal anatomy is important to perform human islet isolation. This
      review is based on clinical experience of more than 900 human islet isolations
      performed over 10 years and aims to highlight pancreatic anatomy and surgical
      techniques in islet processing.

PMID- 21099324
TI  - Expression of secretory phospholipase A 2 in insulitis of human transplanted
      pancreas and its insulinotropic effect on isolated rat islets.
AB  - The expression of secretory phospholipase A 2 (sPLA 2) is induced by inflammatory
      stimuli in various cells, and sPLA 2 contribute to produce proinflammatory lipid
      mediators via hydrolyzing plasma membrane phospholipids into free fatty acid and
      lysophospholipid. We studied the expression of group IIA sPLA 2 in human islets
      of transplanted pancreas before and after the recurrence of type 1 diabetes
      mellitus in a case study. In addition, the effects of exogenous sPLA 2 in
      isolated rat islets were investigated. Expression of group IIA sPLAs was
      immunohistochemicaly investigated in the pancreas graft biopsy specimens. Insulin
      secretion was evaluated by static incubation with different concentrations of
      snake venom sPLA 2. Intracellular free Ca ( 2) + concentration was measured with
      Fura 2 and lysophosphatidylcholine (LPC) contents in islets were determined by
      electrospray ionization-liquid chromatography/mass spectrometry. Group IIA sPLA 2
      was not expressed in islets without insulitis before the recurrence, whereas it
      was diffusely expressed in islets after the recurrence with insulitis. There were
      cells co-expressing group IIA sPLA 2 and insulin. sPLA 2 dose-dependently induced
      insulin secretion in isolated rat islets, which was completely prevented by a
      specific sPLA 2 inhibitor indoxam. The application of sPLA 2 did not affect
      intracellular free Ca ( 2) + concentration in beta cells. On the other hand, LPC
      contents in islets were significantly increased in sPLA 2-treated islets compared
      with untreated islets. Incubation with indoxam suppressed the sPLA 2-induced
      increase of LPC. In conclusion, the present study suggests that group IIA sPLA 2
      may be expressed in islets during insulitis in humans. Although sPLA 2 induced
      insulin secretion in vitro probably via the production of lysophospholipid, the
      significance of this enzyme expression in insulitis remains elusive.

PMID- 21099325
TI  - Experience of islet isolation without neutral protease supplementation.
AB  - BACKGROUND: We have reported improved islet isolation outcomes using a new
      digestion protocol where the pancreas is perfused only with collagenase, and
      neutral protease (NP) is administered during the digestion phase. Since the
      inception of this protocol, we have had some cases where administration of NP was
      not required. Our new protocol was utilized in 94 islet isolations. The timing of
      adding NP was dependent on the progression of digestion but in 10 cases the
      progression was rapid and most islets in the assessment samples were free from
      the exocrine tissue. As a result NP was not added at all for these isolations (no
      NP group). In the remaining 84 isolations, NP was added during digestion phase
      (control group). RESULTS: Pancreata in the each group were digested with a
      similar collagenase dose. Digestion time was shorter in the no-NP (15.0+/-1.8 vs
      19.5+/-0.6 min, P=0.004). At post-digestion, the no-NP had fewer trapped islets
      (10.9+/-2.8 vs 28.1+/-2.4%, P=0.009). Post-purification islet yield was similar
      (355+/-45 x10 ( 3) vs 318+/-17 x10 ( 3) IE, P=0.29). Five preparations in the no
      NP were used for clinical transplantation, leading to a 64.3+/-15.2% reduction in
      insulin usage. Interestingly, cold ischemia time was longer in the no-NP (10.3+/
      0.9 vs 7.9+/-0.4 h, P=0.04). One particular collagenase lot having the highest NP
      activity contamination was used in 7 isolations in the no-NP. Our experience
      indicates that supplementation of collagenase with NP is not always necessary for
      effective isolation. Cold ischemia time and NP contamination should be evaluated
      for optimal NP dosage.

PMID- 21099326
TI  - Mitochondrial proteome analysis reveals altered expression of voltage dependent
      anion channels in pancreatic beta-cells exposed to high glucose.
AB  - Chronic hyperglycemia leads to deterioration of insulin release from pancreatic
      beta-cells as well as insulin action on peripheral tissues. However, the
      mechanism underlying beta-cell dysfunction resulting from glucose toxicity has
      not been fully elucidated. The aim of the present study was to define a set of
      alterations in mitochondrial protein profiles of pancreatic beta-cell line in
      response to glucotoxic condition using 2-DE and tandem mass spectrometry. INS1E
      cells were incubated in the presence of 5.5 and 20 mM glucose for 72 hrs and
      mitochondria were isolated. Approximately 75 protein spots displayed significant
      changes (p < 0.05) in relative abundance in the presence of 20 mM glucose
      compared to controls. Mitochondrial proteins down regulated under glucotoxic
      conditions includes ATP synthase alpha chain and delta chain, malate
      dehydrogenase, aconitase, trifunctional enzyme beta subunit, NADH cytochrome b5
      reductase and voltage-dependent anion-selective channel protein (VDAC) 2. VDAC1,
      75 kDa glucose-regulated protein, heat shock protein (HSP) 60 and HSP10 were
      found to be upregulated. The orchestrated changes in expression of VDACs and
      multiple other proteins involved in nutrient metabolism, ATP synthesis, cellular
      defense, glycoprotein folding and mitochondrial DNA stability may explain
      cellular dysfunction in glucotoxicity resulting in altered insulin secretion.

PMID- 21099327
TI  - Expression and function of cannabinoid receptors in mouse islets.
AB  - The endocannabinoid system plays a key role in energy homeostasis, with agonists
      and antagonists of CB1 receptors acting centrally to stimulate and inhibit food
      intake, respectively. In addition to their established effects on the central
      nervous system, cannabinoid receptor agonists also exert peripheral effects by
      modulating cellular cyclic AMP and calcium levels and there have been reports
      that they regulate beta-cell function. However, the few reports to date on islet
      expression of cannabinoid receptors and effects of agonists on insulin secretion
      have failed to reach a consensus. We have therefore investigated cannabinoid
      receptor expression by mouse islet beta-and alpha-cells and the effects of
      selective receptor agonists on cyclic AMP and calcium levels, and on dynamic
      insulin secretory responses. CB1 and CB2 mRNA and protein expression by islets
      was detected by RT-PCR and western blotting respectively, and cellular location
      of the receptors was identified by immunohistochemistry with insulin and glucagon
      antibody co-staining. Cyclic AMP generation was quantified by enzyme immunoassay
      and changes in calcium levels were measured by microfluorimetry of Fura-2-loaded
      mouse islet cells. Dynamic insulin secretion was quantified by radioimmunoassay
      after perifusion of isolated islets. We found that mouse islets expressed both
      CB1 and CB2 receptors, and they were localised to beta-cells. Activation of mouse
      beta-cell CB1 and CB2 receptors resulted in decreased cyclic AMP, increased
      calcium and potentiation of glucose-stimulated insulin secretion. Thus,
      activation of islet cannabinoid receptors by locally produced endocannabinoids
      such as 2-aminoglycerol may be another regulatory pathway by which islets
      stimulate insulin secretion to maintain glucose homeostasis.

PMID- 21099328
TI  - Electrophysiological effects of osmotic cell shrinkage in rat pancreatic beta
      cells.
AB  - Electrical and secretory activity in the pancreatic beta-cell can be elicited by
      hypotonic cell swelling, due largely to activation of a volume-regulated anion
      channel (VRAC) leading to depolarisation and electrical activity. However, beta
      cell responses to cell shrinkage are less well characterised. The present study
      has examined the effects of osmotic cell shrinkage on rat pancreatic beta-cells.
      Electrical activity and whole-cell current were studied in isolated beta-cells
      using the perforated patch and conventional whole-cell recording techniques.
      Insulin release was measured using intact islets by radioimmunoassay. Exposure to
      a 33% hypertonic bath solution resulted in an initial depolarisation and a period
      of electrical activity. In several cases, this depolarisation was transient and
      was followed by a hyperpolarisation. A similar pattern was observed with insulin
      release. In voltage-clamp experiments, osmotic shrinkage resulted in activation
      of a non-selective cation channel (NSCC) sensitive to inhibition by flufenamic
      acid and Gd3+. It is suggested that activation of this NSCC is responsible for
      the depolarisation evoked by hypertonic media. The secondary hyperpolarisation is
      likely to be the result of inhibition of VRAC activity. These opposing ionic
      effects could underlie the biphasic effect on insulin release following exposure
      to hypertonic media.

PMID- 21099329
TI  - Pim3 negatively regulates glucose-stimulated insulin secretion.
AB  - Pancreatic beta-cell response to glucose stimulation is governed by tightly
      regulated signaling pathways which have not been fully characterized. A screen
      for novel signaling intermediates identified Pim3 as a glucose-responsive gene in
      the beta cell, and here, we characterize its role in the regulation of beta-cell
      function. Pim3 expression in the beta-cell was first observed through microarray
      analysis on glucose-stimulated murine insulinoma (MIN6) cells where expression
      was strongly and transiently induced. In the pancreas, Pim3 expression exhibited
      similar dynamics and was restricted to the beta cell. Perturbation of Pim3
      function resulted in enhanced glucose-stimulated insulin secretion, both in MIN6
      cells and in isolated islets from Pim3-/- mice, where the augmentation was
      specifically seen in the second phase of secretion. Consequently, Pim3-/- mice
      displayed an increased glucose tolerance in vivo. Interestingly, Pim3-/- mice
      also exhibited increased insulin sensitivity. Glucose stimulation of isolated
      Pim3-/- islets resulted in increased phosphorylation of ERK1/2, a kinase involved
      in regulating beta-cell response to glucose. Pim3 was also found to physically
      interact with SOCS6 and SOCS6 levels were strongly reduced in Pim3-/- islets.
      Overexpression of SOCS6 inhibited glucose-induced ERK1/2 activation, strongly
      suggesting that Pim3 regulates ERK1/2 activity through SOCS6. These data reveal
      that Pim3 is a novel glucose-responsive gene in the beta cell that negatively
      regulates insulin secretion by inhibiting the activation of ERK1/2, and through
      its effect on insulin sensitivity, has potentially a more global function in
      glucose homeostasis.

PMID- 21099330
TI  - Effect of inborn pancreatic islet deficit in the Munich Wister Fromter rat.
AB  - The total mass of pancreatic islet cells is a critical factor in glucose
      metabolic control. The aim of the present study was to investigate whether in the
      Munich Wistar Fromter (MWF) rat, beside a reduction in the number of nephrons,
      there are also alterations in the number of pancreatic islets and of beta cell
      mass. We also examined glucose metabolism, both in normal conditions and
      following intravenous glucose injection. The number of islets per pancreas,
      estimated by morphometrical analysis, was significantly lower in MWF rats than in
      Wistar rats (3,501+/-1,285 vs. 7,259+/-2,330 islet/rat, respectively). Also the
      mean number of islets per gram of body weight was significantly lower in MWF rats
      than in Wistar rats (18+/-7 in MWF rats vs. 28+/-10 islets/g bw in Wistar rats).
      Morphometric analysis of beta cell mass showed an average of 77.1+/-7% islet
      cells staining for insulin in MWF rats and 83.9+/-2.1% in the control Wistar
      rats. Despite the lower number of islets and beta cells, MWF and Wistar rats had
      comparable fasting blood glucose levels but significant differences in blood
      glucose following an intraperitoneal glucose tolerance test. In summary,
      pancreatic islets of MWF and Wistar rats showed a marked difference in
      morphometrical characteristics. While this difference is not associated with
      blood glucose levels, glucose metabolism after IPGTT between MWF and Wistar rats
      is significantly different. These data suggest that an inborn deficit in beta
      cell mass of about 60% is responsible for altered glucose metabolism and could
      favor the development of diabetes.

PMID- 21099331
TI  - An emerging role for NAADP-mediated Ca2+ signaling in the pancreatic beta-cell.
AB  - Several recent reports, including one in this journal, have reignited the debate
      about whether the calcium-mobilizing messenger, nicotinic adenine nucleotide
      diphosphate (NAADP) plays a central role in the regulation of calcium signalling
      in pancreatic beta-cell. These studies have highlighted a role for NAADP-induced
      Ca(2+) mobilization not only in mediating the effects of the incretin, GLP-1 and
      the autocrine proliferative effects of insulin, but also possibly a fundamental
      role in glucose-mediated insulin secretion in the pancreatic beta-cell.

PMID- 21099332
TI  - A TRP channel contributes to insulin secretion by pancreatic beta-cells.
AB  - The release of insulin by pancreatic beta cells involves a complex interplay of
      conductances that generate oscillations and drive secretion. A recent report
      identifies a new player in this process, the ion channel TRPM5. TRPM5 was
      originally identified in taste cells, where it forms a Ca(2+)-activated cation
      channel that is required for sensory responses to bitter and sweet tastes. New
      research now shows that TRPM5 is expressed within the pancreatic islets of
      Langerhans, where it regulates the frequency of Ca(2+) oscillations and
      contributes to insulin release by beta-cells.

PMID- 21099333
TI  - Defining the regulation of IL-1beta- and CHOP-mediated beta-cell apoptosis.
AB  - Diabetes is a multifaceted metabolic disorder that can be caused by pancreatic
      beta-cell destruction (type I diabetes) and/or heightened by beta-cell failure
      (type II diabetes). The gross clinical and physiological characteristics of the
      disease are well characterized, and viable treatment options can drastically
      alter the course and effects of the disease. However, the molecular events
      occurring within the beta-cell that cause or contribute to diabetes are not
      adequately understood, especially in terms of the interplay between the
      physiological signals that facilitate disease development. A recent report,
      focused on a mechanism by which IL-1beta induces beta-cell apoptosis, underscores
      the complexity of the molecular events that may cause or affect the progression
      of diabetes. This commentary summarizes aspects of this report, discusses an
      example of the complexity of beta-cell regulation and proposes more frequent use
      of complex in vitro systems that more closely mimic in vivo conditions so that
      greater advances can be made toward understanding the molecular mechanisms
      contributing to diabetes. Understanding the molecular etiology of beta-cell
      dysfunction will likely enhance the possibility of developing novel diabetes
      therapeutic interventions for diabetes.

PMID- 21099334
TI  - Adding efficiency: the role of the CAN ion channels TRPM4 and TRPM5 in pancreatic
      islets.
AB  - Insulin secretion in beta-pancreatic cells after glucose stimulation requires the
      concerted action of a number of different ion channels. The main players seem to
      be the ATP sensitive K(+) (KATP-) channels, and voltage gated ion channels that
      drive Ca(2+) influx into beta-cells. Recently two calcium activated nonselective
      (CAN) cation channels (TRPM4 and TRPM5) have been shown to influence efficient
      insulin response upon glucose stimulation. This addendum summarizes the data
      known for these two TRP channels in beta-cells, discusses some of the remaining
      open questions and addresses a possible scenario that involves and integrates the
      triggering and amplifying pathway of glucose mediated insulin secretion.

PMID- 21099335
TI  - A role for islet somatostatin in mediating sympathetic regulation of glucagon
      secretion.
AB  - AIMS/HYPOTHESIS: Somatostatin (SST) released from islet delta-cells inhibits both
      insulin and glucagon secretion but the role of this tonic inhibition is unclear.
      In this study we investigated whether delta-cell SST may facilitate sympathetic
      regulation of glucagon secretion as part of an 'accelerator/brake' mechanism.
      METHODS: The secretory characteristics of islets isolated from SST-deficient (Sst
      /-) and control mouse islets were assessed in static incubation studies. Glucagon
      and SST release was measured by radioimmunoassay (RIA). RESULTS: Arginine
      stimulated both glucagon and SST release from control mouse islets whereas the
      sympathetic neurotransmitter noradrenaline (NA) increased glucagon secretion but
      inhibited SST release in the presence of 2 mmol/l glucose or 20 mmol/l arginine.
      Experiments were performed using Sst-/- islets to assess whether the reduction of
      SST secretion by NA offers an indirect mechanism of enhancing glucagon release in
      response to sympathetic activation. Arginine-induced but not NA-induced glucagon
      release from Sst-/- islets was significantly increased compared to controls. In
      combination, NA enhanced arginine-induced release from both groups of mouse
      islets but to a greater extent in control islets, leading to similar overall
      levels of glucagon release. The responsiveness of Sst-/- islets to NA was thus
      blunted under stimulatory but not sub-stimulatory conditions of SST release.
      CONCLUSIONS: Our data suggest that sympathetic activation of glucagon release may
      be partly mediated by an indirect effect on SST secretion, where the tonic
      inhibition by delta-cell SST on alpha-cells is removed, facilitating precise and
      substantial changes in glucagon release in response to NA.

PMID- 21099337
TI  - Increased beta-cell volume in mice fed a high-fat diet: a dynamic study over 12
      months.
AB  - As we previously demonstrated, there is an adaptive increase in insulin secretion
      in insulin resistance in the model of high-fat fed female mice. Since it is
      assumed that islets also adapt to insulin resistance with beta-cell expansion, we
      have now examined beta volume in this experimental model. Female C57BL/6JBomTac
      mice were therefore fed a high-fat diet (60% fat from lard) for three, six or
      twelve months and beta cell volume was estimated as beta-cell area per islet,
      individual beta-cell size, and beta-cell number per islet. Control animals were
      fed a normal chow (11% fat). We found that beta-cell area per islet and total
      number of beta cells per islet were increased already after three months of high
      fat feeding and that this increase was sustained throughout the twelve month
      study period. In contrast, individual beta cell size showed a dynamic pattern
      with a reduction after three months followed by increase after six and twelve
      months. The number of apoptosis (caspase-3) positive beta-cells was reduced after
      three months, whereas there was no difference in proliferation (Ki-67) positive
      cells, although these were generally rarely observed. Thus, we conclude that
      insulin resistance accompanying high-fat feeding in mice is followed by
      progressive beta-cell expansion as evident by early increased islet beta-cell
      volume and total number of beta-cells, whereas individual beta-cell size showed a
      dynamic response. The model is also associated with an early reduced apoptosis,
      which may contribute to the increased beta cell volume.

PMID- 21099338
TI  - beta-Cell adaptation/dysfunction in an animal model of dyslipidemia and insulin
      resistance induced by the chronic administration of a sucrose-rich diet.
AB  - Glucose stimulated insulin secretion (GSIS) was different in rats chronically fed
      a sucrose-rich diet (SRD) for 3 or 30 wk. This work proposes possible mechanisms
      underlying insulin secretion changes from beta-cell throughout these feeding
      periods. In isolated islets of rats fed the SRD or a control diet (CD) we
      examined: 1- the glucokinase and hexokinase activities and their protein mass
      expression; 2- pyruvate dehydrogenase activity; 3- uncoupling protein 2 (UCP2)
      and peroxisome proliferators-activated receptor gamma (PPAR gamma) protein mass
      expression. At 3 wk on diet the SRD-fed rats showed: a marked increase in the
      first peak of GSIS; increased glucokinase protein mass expression without changes
      in glucokinase and hexokinase activities; increased PPARgamma protein mass
      expression without changes in the UCP2 protein mass expression. No changes in
      either glucose oxidation and triglyceride content within the beta-cell were
      observed. After 30 wk of feeding, a significant decrease of both glucokinase
      activity and its protein mass expression was accompanied by altered glucose
      oxidation, a triglyceride increase within the beta-cell and a significant
      increase of PPARgamma and UCP2 protein mass expression. Moreover GSIS depicted an
      absence of the first peak with an increase in the second phase. Finally, the SRD
      chronic administration altered GSIS by different mechanisms depending on the time
      on diet. At an early stage, the increased protein mass expression of the
      glucokinase and a fatty acid cooperative effect inducing PPARgamma expression
      seem to be the mechanisms involved. At a late stage, glucolipotoxicity appears to
      be the cellular mechanism contributing to progressive beta-cell dysfunction.

PMID- 21099339
TI  - Expression and functional roles of guanylate cyclase isoforms in BRIN-BD11 beta
      cells.
AB  - This study has assessed the expression and functional significance of cGMP
      dependent signalling components in BRIN-BD11 cells. RT-PCR analysis revealed the
      expression of two subunits of soluble guanylate cyclase (sGC) suggesting the
      presence of an alpha2/beta1 heterodimer. The expression of three particulate
      guanylate cyclases (pGC) was also detected (GC-A, GC-B and GC-C), as well as two
      cGMP-selective PDE isoforms (PDE5A and PDE9). Stimulation of BRIN-BD11 cells with
      agonists selective for sGC (NO, YC-1 and BAY 41-2272), GC-A (atrial natriuretic
      peptide (ANP) or GC-C (guanylin) caused an elevation in cGMP, and in the case of
      sGC, this was blocked by the selective inhibitor 1H-[1,2,4]oxadiazolo-[4,3
      a]quinoxalin-1-one (ODQ). The stimulatory effects of each activator on cGMP
      levels were further potentiated by the PDE5A inhibitor, zaprinast. Treatment of
      cells with sGC activators induced a loss of viability and increased insulin
      secretion. However these effects were not attenuated by ODQ suggesting that they
      were independent of a rise in cGMP. A modest increase in beta-cell death and
      insulin secretion were also observed in guanylin and ANP treated cells, although
      the latter only reduced cell viability in the presence of a PDE5A inhibitor.
      Taken together, the data reveal that BRIN-BD11 cells express several functionally
      active enzymes capable of modulating cGMP levels, and they imply that signalling
      through these proteins may impact upon beta-cell viability. The results further
      suggest that pGC isozymes can also regulate insulin secretion but that the pool
      of cGMP controlling insulin release is small relative to the global cGMP
      concentration in the cell.

PMID- 21099336
TI  - Aging induces a distinct gene expression program in mouse islets.
AB  - The role of aging in the pathogenesis of type 2 diabetes remains poorly
      understood. In the past adult beta-cells were assumed to undergo frequent
      turnover. However, we find that beta-cell turnover declines to very low levels in
      middle-aged mice. We therefore hypothesized that aged islets could exhibit a
      distinct gene expression program. We compared gene expression in islets from
      young mice to islets from aged mice under basal conditions. Aging was associated
      with differential expression of many genes in islets, including mRNAs encoding
      for chromatin remodeling components, RNA binding proteins, and pancreatic
      endocrine transcription factors. We previously observed that cell cycle entry of
      beta-cells is severely restricted by middle age, with minimal of beta-cell
      proliferation in response to regenerative stimuli such as 50% partial
      pancreatectomy. To characterize the effect of age in adaptive beta-cell
      proliferation, we measured gene expression in islets from young mice after
      pancreatectomy. As expected, partial pancreatectomy induced differential
      expression of many genes, including those encoding Reg (regenerating) proteins.
      Surprisingly, partial pancreatectomy also induced expression of Reg genes in
      islets from aged mice, which have greatly reduced capacity for adaptive beta-cell
      proliferation. However, there was little overlap (besides the Reg genes) in
      between the partial pancreatectomy induced islet genes in young mice versus old
      mice. Thus, partial pancreatectomy does not induce the same gene expression
      program in young mice vs old mice. Taken together, our results reveal that aged
      islets exhibit a unique gene expression signature that could contribute to the
      limited regenerative capacity of mature beta-cells.

PMID- 21099340
TI  - The multiple alternatives of intracellular calcium signaling: a functionally
      distinct RyR splicing variant in pancreatic islets.
AB  - The sophistication of intracellular Ca ( 2+) signalling reflects the necessity
      for the many different types of cells to fine tuning their specific activities.
      This can, at least in part, be explained by the molecular complexity of the Ca (
      2+) signalling machinery, consisting of different intracellular Ca ( 2+) release
      channel types, each including multiple isoforms and alternative splicing
      variants. This commentary will go over the main points concerning expression and
      functional characterization of alternative splicing variants of inositol 1,4,5
      trisphosphate and ryanodine receptor isoforms. Many of these variants display
      specific activation or regulatory features. In addition, dominant negative
      effects of non-functional alternative splicing variants have been also described
      for both InsP3Rs and RyRs channels. Recently, a novel RyR2 transcript has been
      identified by Takasawa and co-workers in pancreatic islets. This novel RyR2
      transcript has been proposed to act as an intracellular target for cADPR
      signalling, which has been demonstrated to be important for insulin secretion.
      Future characterization of this RyR2 transcript may represent a significant
      advancement in understanding the mechanisms underlying regulation of Ca ( 2+)
      release by cADPR.

PMID- 21099341
TI  - Characterization of the gating brake in the I-II loop of CaV3 T-type calcium
      channels.
AB  - Our interest was drawn to the I-II loop of Cav3 channels for two reasons:  one,
      transfer of the I-II loop from a high voltage-activated channel (Cav2.2) to a low
      voltage-activated channel (Cav3.1) unexpectedly produced an ultra-low voltage
      activated channel; and two, sequence variants of the I-II loop found in childhood
      absence epilepsy patients altered channel gating and increased surface expression
      of Cav3.2 channels. To determine the roles of this loop we have studied the
      structure of the loop and the biophysical consequences of altering its structure.
      Deletions localized the gating brake to the first 62 amino acids after IS6 in
      all three Cav3 channels, establishing the evolutionary conservation of this
      region and its function.  Circular dichroism was performed on a purified fragment
      of the I-II loop from Cav3.2 to reveal a high alpha-helical content.  De novo
      computer modeling predicted the gating brake formed a helix-loop-helix structure.
      This model was tested by replacing the helical regions with poly-proline-glycine
      (PGPGPG), which introduces kinks and flexibility.  These mutations had profound
      effects on channel gating, shifting both steady-state activation and inactivation
      curves, as well as accelerating channel kinetics.  Mutations designed to preserve
      the helical structure (poly-alanine, which forms alpha-helices) had more modest
      effects.  Taken together, we conclude the second helix of the gating brake
      establishes important contacts with the gating machinery, thereby stabilizing a
      closed state of T-channels, and that this interaction is disrupted by
      depolarization, allowing the S6 segments to spread open and Ca (2+) ions to flow
      through.

PMID- 21099342
TI  - Open- and closed-state fast inactivation in sodium channels: differential effects
      of a site-3 anemone toxin.
AB  - The role of sodium channel closed-state fast inactivation in membrane
      excitability is not well understood. We compared open- and closed-state fast
      inactivation, and the gating charge immobilized during these transitions, in
      skeletal muscle channel hNa(V)1.4. A significant fraction of total charge
      movement and its immobilization occurred in the absence of channel opening.
      Simulated action potentials in skeletal muscle fibers were attenuated when pre
      conditioned by sub-threshold depolarization. Anthopleurin A, a site-3 toxin that
      inhibits gating charge associated with the movement of DIVS4, was used to assess
      the role of this voltage sensor in closed-state fast inactivation. Anthopleurin
      elicited opposing effects on the gating mode, kinetics and charge immobilized
      during open- versus closed-state fast inactivation. This same toxin produced
      identical effects on recovery of channel availability and remobilization of
      gating charge, irrespective of route of entry into fast inactivation. Our
      findings suggest that depolarization promoting entry into fast inactivation from
      open versus closed states provides access to the IFMT receptor via different rate
      limiting conformational translocations of DIVS4.

PMID- 21099343
TI  - Mitotic DNA damage targets the Aurora A/TPX2 complex.
AB  - We have previously shown that the DNA damage-induced G2 arrest is contributed by
      inhibition of Aurora A (AurA) and that transduction of active AurA into arrested
      cells allows bypassing the block through reactivation of CDK1. In this study, we
      investigated the mechanism of DNA damage-induced AurA inhibition. We provide
      evidence that ionizing radiation (IR) administered in mitosis, a time when AurA
      protein and enzymatic activity reach peak levels, impairs interaction with the
      partner TPX2, leading to inactivation of the kinase through dephosphorylation of
      AurA T-loop residue, T288. We find that decreased AurA-TPX2 complex formation in
      response to irradiation results from reduced cellular levels of TPX2, an effect
      that is both contributed by increased APC/CDH1-dependent protein degradation and
      decreased translation of TPX2 mRNA.

PMID- 21099344
TI  - Deregulated expression of sprouty2 and microRNA-21 in human colon cancer:
      Correlation with the clinical stage of the disease.
AB  - Sprouty protein is a novel feedback regulator involved in downstream inactivation
      of several growth factor receptor pathways. Sprouty2 (Spry2) protein was shown to
      be downregulated in human cancers. High levels of microRNA-21 (miRNA-21)
      expression have been associated with poor survival and poor response to adjuvant
      chemotherapy in cancer patients. But the effect of Spry2 in human colon cancer
      remained unknown. Paired tumor and normal mucosa samples from patients were
      examined for their expression of Spry2 mRNA and miRNA-21 by real-time
      quantitative RT-PCR analysis. Our results show that Spry2 was downregulated in
      human colon cancer, and its expression levels were lower in advanced-stage tumors
      than in early-stage tumors. There was a negative correlation between the
      expression levels of Spry2 and miRNA-21. Furthermore, overexpression of Spry2
      suppressed the growth and migration of colon cancer cells with a concomitant
      increase in PTEN expression and reduction of Akt and MAPK phosphorylation. Spry2
      inhibited the growth and tumorigenesis of colon cancer cells in vivo.
      Conclusively, we show for the first time that Spry2 expression is downregulated
      and miRNA-21 is upregulated in the clinical samples of colon cancer, which
      correlates with clinical stage of disease. Thus, Spry2 functions as a tumor
      suppressor in colon cancer.

PMID- 21099345
TI  - MMP7 and activation of IGF-1R: a new insight into anti-EGFR therapeutic
      resistance in metastatic colorectal cancer.

PMID- 21099346
TI  - Differential inhibition of transmembrane 4 L six family member 5 (TM4SF5)
      mediated tumorigenesis by TSAHC and sorafenib.
AB  - Two separate clinical studies of advanced hepatocarcinoma patients recently
      reported that the multikinase inhibitor sorafenib (nexavar) could extend survival
      of the patients only by 2-3 months. We also previously demonstrated that 4'-(p
      toluenesulfonylamido)-4-hydroxychalcone (TSAHC) blocks the multilayer growth and
      migration mediated by TM4SF5, which is highly expressed in approximately 80% of
      Korean hepatocarcinoma patients. Therefore, we wondered how TSAHC might be
      different from sorafenib to deal with hepatocarcinoma in terms of the therapeutic
      characteristics including specificity for TM4SF5. TM4SF5 is previously shown to
      mediate tumorigenesis through cytosolic p27Kip1-mediated inactivation of RhoA,
      epithelial-mesenchymal transition, multilayer growth, migration, invasion, and
      tumor angiogenesis. In this study, TSAHC and two derivatives showed similar
      antagonistic activities against TM4SF5-mediated signaling and multilayer growth
      in vitro and anti-tumorigenic activity even in early stages of TM4SF5-mediated
      tumor formation in nude mice. Meanwhile, sorafenib was only effective much later
      in tumorigenesis in vivo and affected in vitro proliferation in a TM4SF5
      independent manner. Altogether, these observations suggest that TSAHC may be a
      promising anti-tumorigenic reagent, especially against TM4SF5-mediated
      hepatocarcinoma.

PMID- 21099347
TI  - Antibody nomenclature: from IMGT-ONTOLOGY to INN definition.

PMID- 21099348
TI  - Co-expression of matrix metalloproteinase-7 (MMP-7) and phosphorylated insulin
      growth factor receptor I (pIGF-1R) correlates with poor prognosis in patients
      with wild-type KRAS treated with cetuximab or panitumumab: a GEMCAD study.
AB  - BACKGROUND: By transactivacion, phosphorylated insulin growth factor receptor I
      (IGF-1R) can activate epidermal growth factor receptor (EGFR). MMP-7, produced by
      colorectal cancer cells, also can activate IGF-1R by degrading IGFBP-3 and
      releasing IGF-I. METHODS: A cohort of patients (pts) with advanced colorectal
      cancer (CRC), under second- or third-line treatment with cetuximab or
      panitumumab, was tested using immunohistochemistry for expression of the
      activated form of IGF-1R (p-IGF-1R) and MMP-7. KRAS and BRAF mutation status was
      determined by sequencing and allelic discrimination analysis, respectively.
      Analyses were performed in primary CRC tumor samples or metastases, and the
      association of immunohistochemistry findings, mutational results, and treatment
      outcomes was investigated in both univariate and multivariate analyses. RESULTS:
      Expression of activated IGF-1R and MMP-7 was observed in 51 and 49% of pts,
      respectively. Co-expression of MMP-7 and pIGF-1R (double positivity, DP) was
      observed in 28 pts (25%). There was no association between KRAS or BRAF
      mutational status and DP (p=0.52). Pts with DP responded more poorly to first
      line chemotherapy (p=0.005) and to anti-EGFR treatment (p=0.01) than non-DP pts.
      In wild type (WT) KRAS pts, those with DP have poorer PFS (2.7 months vs. 3.5m,
      p=0.036; HR 1.98, 95% CI 1.05-3.75) and OS (6.4 months vs. 8.6 m, p=0.010; HR
      2.33, 95%CI 1.23-4.43) in the adjusted multivariate analysis. CONCLUSIONS: Our
      study suggests that concomitant expression of MMP-7 and activation of p-IGF-1R
      (DP) correlates with poor prognosis in WT KRAS pts treated with anti-EGFR.

PMID- 21099349
TI  - Anti-autophagic Bcl-2: Not just an innocent bystander.
AB  - Bcl-2, originally identified as a universal inhibitor of apoptotic cell death,
      has since been implicated in suppressing autophagy, the cell's quality control
      mechanism. Our recent study demonstrates that the anti-autophagic aspect of Bcl-2
      can function as a promoter of oncogenic growth, independently of its role in
      apoptosis signaling. It is likely that the increase in Bcl-2 often seen in breast
      and other cancers might render cells error-prone by blunting autophagy, while
      concomitantly keeping damaged cells alive. The outcome of such a 'double hit' of
      Bcl-2 may synergistically promote tumor growth and increase the chance of cancer
      development and drug resistance.

PMID- 21099350
TI  - Role of the pituitary tumor transforming gene 1 in the progression of
      hepatocellular carcinoma.
AB  - In order to demonstrate the role of the pituitary tumor transforming gene 1
      (PTTG1) in the development of hepatocellular carcinoma (HCC) and its value as a
      molecular target for cancer therapy, we analyzed the expression of PTTG1 mRNA and
      protein, and their relation to clinicopathological characteristics and basic
      fibroblast growth factor (bFGF) expression in HCC. It was observed that the level
      of PTTG1 mRNA and the positive rate of PTTG1 protein in cancerous tissues were
      significantly higher than that in adjacent non-cancerous tissues (both P< 0.001).
      The PTTG1 protein levels were correlated with several clinicopathological
      parameters, including alpha-fetoprotein level, portal vein tumor thrombosis,
      tumor stage, and bFGF protein level (P< 0.05). The proliferation indices were
      significantly less and the apoptotic rates were significantly higher in the HepG2
      and SMMC-7721 cells treated with PTTG1 siRNA transfection than their
      untransfected counterparts. The expressions of Caspase-3, Bax, p21 and p53 in
      HepG2 and SMMC-7721 cells were significantly increased after siRNA knockdown of
      PTTG1 expression. In conclusion, the PTTG1 gene is up-regulated in the cancerous
      tissue from patients with HCC and involved in the progression of HCC. Inhibiting
      PTTG1 expression decreases cell proliferation and induces apoptosis in hepatic
      cancer cell lines, indicating that PTTG1 may be a new therapeutic target for HCC
      treatment.

PMID- 21099351
TI  - TGFbeta-dependent induction of interleukin-11 and interleukin-8 involves SMAD and
      p38 MAPK pathways in breast tumor models with varied bone metastases potential.
AB  - We have delineated TGFbeta signaling pathways in the production of osteolytic
      factors interleukin-8 and interleukin-11 in breast cancer cells with different
      bone metastases potential. Bone seeking MDA-MB-231(hm) cells expressed higher
      levels of IL-11, but lower levels of IL-8 compared to MDA-MB-231 cells. MCF-7
      cells (mainly osteoblastic) did not express IL-8 or IL-11; MDA-MB-468 cells
      (weakly metastatic) expressed IL-8, but not IL-11. The up-regulation of IL-11 and
      IL-8 was associated with the rapid activation of SMAD2/3 and p38 MAPK through the
      TGFbeta/TGFbetaR system. Analysis of TGFbeta receptors indicated that MCF-7 cells
      do not express TGFbetaRII, and MDA-MB-468 cells do not express SMAD4.
      Inactivation of SMAD4 or p38PMAPK gene via RNAi resulted in the inhibition of IL
      11 and IL-8 production in MDA-MB-231(hm) cells; and over-expression of SMAD4 gene
      resulted in IL-11 production in MDA-MB-468 cells. TGFbeta-1 induced SMAD3
      translocation to the nuclei in MDA-MB-231, MDA-MB-231(hm) as well as in SMAD4
      deficient MDA-MB-468, indicating that an alternate non-canonical pathway could be
      responsible for TGFbeta-1 induced cytokine production in MDA-MB-468 cells. Thus,
      four breast cancer cell lines used in this study show differential expression and
      up-regulation of the osteolytic factors in response to TGFbeta-1 that involves
      both SMAD pathway, a non-canonical SMAD pathway, as well as p38 MAPK pathways.

PMID- 21099352
TI  - The TOLL of inflammation in multiple myeloma.

PMID- 21099354
TI  - Phosphorylation of histone H3 serine 10 in early mouse embryos: active
      phosphorylation at late S phase and differential effects of ZM447439 on first two
      embryonic mitoses.
AB  - Cell division in mammalian cells is regulated by Aurora kinases. The activity of
      Aurora A is indispensable for correct function of centrosomes and proper spindle
      formation, while Aurora B for chromosome biorientation and separation. Aurora B
      is also responsible for the phosphorylation of histone H3 serine 10 (H3S10Ph)
      from G2 to metaphase. Data concerning the Aurora B activity and H3S10Ph in
      embryonic cells are limited to primordial and maturing oocytes and advanced
      pronuclei in zygotes. In the present study we have analyzed H3S10Ph in 1- and 2
      cell mouse embryos. We show that H3S10 remains phosphorylated at anaphase and
      telophase of the second meiotic division, as well as during the anaphase and
      telophase of the first and second embryonic mitoses. At late G1 H3S10 is
      dephosphorylated and subsequently phosphorylated de novo at late S phase of the
      first and second cell cycle. These results show that the H3S10
      phosphorylation/dephosphorylation cycle in embryonic cells is different than in
      somatic cells. The behaviour of thymocyte G0 nuclei introduced into ovulated
      oocytes and early 1-cell parthenogenotes confirms that kinases responsible for de
      novo H3S10 phosphorylation, most probably Aurora B,  are active until G1 of the
      first cell cycle of mouse embryo. The inhibition of Aurora kinases by ZM447439
      caused abnormalities both in the first and second mitoses. However, the
      disturbances in each division differed, suggesting important differences in the
      control of these mitoses. In ZM447439-treated mitotic zygotes Mad2 protein
      remained continuously present on kinetochores, what confirmed that spindle
      checkpoint remained active.

PMID- 21099353
TI  - Rb-dependent cellular senescence, multinucleation and susceptibility to oncogenic
      transformation through PKC scaffolding by SSeCKS/AKAP12.
AB  - A subset of AKAPs (A Kinase Anchoring Proteins) regulate signaling and
      cytoskeletal pathways through the spaciotemporal scaffolding of multiple protein
      kinases (PK) such as PKC and PKA, and associations with the plasma membrane and
      the actin-based cytoskeleton. SSeCKS/Gravin/Akap12 expression is severely
      downregulated in many advanced cancers and exhibits tumor- and metastasis
      suppressing activity. akap12-null (KO) mice develop prostatic hyperplasia with
      focal dysplasia, but the precise mechanism how Akap12 prevents oncogenic
      progression remains unclear. Here, we show that KO mouse embryonic fibroblasts
      (MEF) exhibit premature senescence marked by polyploidy and multinucleation, and
      by increased susceptibility to oncogenic transformation. Although p53 and Rb
      pathways are activated in the absence of Akap12, senescence is dependent on Rb.
      Senescence is driven by the activation of PKCalpha, which induces p16(Ink4a)/Rb
      through a MEK-dependent downregulation of Id1, and PKCdelta, which downregulates
      Lats1/Warts, a mitotic exit network kinase required for cytokinesis. Our data
      strongly suggest that Akap12 controls Rb-mediated cell aging and oncogenic
      progression by directly scaffolding and attenuating PKCalpha/delta.

PMID- 21099355
TI  - Ectopic expression of human Cdk2 and its yeast homolog, Ime2, is deleterious to
      Saccharomyces cerevisiae.
AB  - Entry into and precise progression through the cell cycle depends on the
      sequential expression and activation of cyclin dependent kinases (CDK). In
      accord, CDK dysregulation is a hallmark of many cancers. The function of Cdk2 is
      still an enigma as in vitro studies revealed that it is required for S phase
      entry, whereas in vivo studies showed that Cdk2 is not an essential gene.
      Moreover, unlike other Cdks, or its cyclin E regulator, Cdk2-overexpressing
      tumors were reported only in one type of tumor. In this report we used budding
      yeast as a tool to explore Cdk2 function. We showed that hCdk2 promoted S phase
      in cells carrying a temperature-sensitive mutation in yCDK1, albeit, only when
      expressed at low or moderate levels. Overexpression of hCdk2 resulted in a defect
      in the G1 to S transition and a reduction in viability. The same phenotypes were
      observed in cells overexpressing its yeast functional homolog, Ime2, which is a
      meiosis-specific CDK-like kinase. A genetic interaction with the DNA damage
      checkpoint was demonstrated by showing an increased toxicity of hCdk2 and Ime2 in
      RAD53-deleted cells, and delayed Rad53 activation in response to MMS treatment in
      cells overexpressing hCdk2 or Ime2.

PMID- 21099357
TI  - Genetic instability in human induced pluripotent stem cells: classification of
      causes and possible safeguards.

PMID- 21099358
TI  - Prion and TNFalpha: TAC(E)it agreement between the prion protein and cell
      signaling.
AB  - Prion diseases are rare and fatal neurodegenerative disorders that occur when the
      cellular prion protein (PrPC) is converted into a conformationally modified
      isoform that originates the novel infectious agent, called prion. Although much
      information is now available on the different routes of prion infection, both the
      mechanisms underlying prion neurotoxicity and the physiologic role of PrPC remain
      unclear. By use of a novel paradigm, we have shown in a recent paper that-
      following a myotoxin-induced degenerative challenge--PrPC is implicated in the
      morphogenesis of the skeletal muscle of adult mice. PrPC accomplished this task
      by modulating signaling pathways central to the myogenic process, in particular
      the p38 kinase pathway. The possibility that PrPC acts in cell signaling has
      already been suggested after in vitro studies. Using our in vivo approach, we
      have instead provided proof of the physiologic relevance of PrPC commitment in
      signaling events, and that PrPC likely performed the task by controlling the
      activity of the enzyme (TACE) secreting the signaling TNFalpha molecule. After a
      brief summary of our data, here we will discuss the suggestion, arising from our
      and other recent findings, implying that regulation of TACE, and of other members
      of the protease family TACE belongs to, may be exploited by PrPC in different
      cell contexts. Notably, this advancement of knowledge on PrPC physiology could
      also shed light on the defense mechanisms against the onset of a more common
      neurodegenerative disorder than prion disease, such as Alzheimer disease.

PMID- 21099356
TI  - Female infertility in PDE3A(-/-) mice: polo-like kinase 1 (Plk1) may be a target
      of protein kinase A (PKA) and involved in meiotic arrest of oocytes from PDE3A(-/
      ) mice.
AB  - Mechanisms of cAMP/PKA-induced meiotic arrest in oocytes are not completely
      identified. In cultured, G2/M-arrested PDE3A(-/-) murine oocytes, elevated PKA
      activity was associated with inactivation of Cdc2 and Plk1, and inhibition of
      phosphorylation of histone H3 (S10) and of dephosphorylation of Cdc25B (S323) and
      Cdc2 (Thr14/Tyr15). In cultured WT oocytes, PKA activity was transiently reduced
      and then increased to that observed in PDE3A(-/-) oocytes; Cdc2 and Plk1 were
      activated, phosphorylation of histone H3 (S10) and dephosphorylation of Cdc25B
      (S323) and Cdc2 (Thr14/Tyr15) were observed. In WT oocytes, PKAc were rapidly
      translocated into nucleus, and then to the spindle apparatus, but in PDE3A(-/-)
      oocytes, PKAc remained in the cytosol. Plk1 was reactivated by incubation of
      PDE3A(-/-) oocytes with PKA inhibitor, Rp-cAMPS. PDE3A was co-localized with Plk1
      in WT oocytes, and co-immunoprecipitated with Plk1 in WT ovary and Hela cells.
      PKAc phosphorylated rPlk1 and Hela cell Plk1 and inhibited Plk1 activity in
      vitro. Our results suggest that PKA-induced inhibition of Plk1 may be critical in
      oocyte meiotic arrest and female infertility in PDE3A(-/-) mice.

PMID- 21099359
TI  - BRCA1 modulates the expression of hnRNPA2B1 and KHSRP.
AB  - Inactivation of the breast cancer susceptibility gene 1 (BRCA1) plays a
      significant role in the development of a subset of familial breast and ovarian
      cancers, but increasing evidence points to a role also in sporadic tumors. BRCA1
      is a multifunctional nuclear protein involved in the regulation of many nuclear
      cellular processes, including DNA repair, cell cycle, transcription and chromatin
      remodeling. To identify novel proteins participating in the BRCA1 network, two
      dimensional gel electrophoresis and MALDI-TOF mass spectrometry were used to
      compare the nuclear-enriched proteome map of BRCA1-deficient and BRCA1-proficient
      cell lines. Five differentially expressed polypeptides were identified and two of
      them, hnRNPA2B1 and KHSRP, turned out to be involved in mRNA and miRNA
      metabolism. qRT-PCR analyses indicated that the hnRNPA2B1 and KHSRP levels
      increased in response to BRCA1 loss and restoration of BRCA1 expression in BRCA1
      null cells reverted hnRNPA2B1 and KHSRP up-regulation. Interrogation of publicly
      available transcriptional profiling datasets revealed that both genes were
      actually over-expressed in BRCA1 mutated tumors. Overall, our results indicate
      that BRCA1 modulates the expression of two proteins involved in the processing of
      RNA, highlighting the complex nature of BRCA1-associated tumor suppressor
      function and disclosing a novel mechanism by which BRCA1 may affect
      transcription.

PMID- 21099360
TI  - Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in
      fission yeast.
AB  - In fission yeast, replication fork arrest activates the replication checkpoint
      effector kinase Cds1(Chk2/Rad53) through the Rad3(ATR/Mec1)-Mrc1(Claspin)
      pathway. Hsk1, the Cdc7 homologue of fission yeast required for efficient
      initiation of DNA replication, is also required for Cds1 activation. Hsk1 kinase
      activity is required for induction and maintenance of Mrc1 hyperphosphorylation,
      which is induced by replication fork block and mediated by Rad3. Rad3 kinase
      activity does not change in an hsk1 temperature-sensitive mutant, and Hsk1 kinase
      activity is not affected by rad3 mutation. Hsk1 kinase vigorously phosphorylates
      Mrc1 in vitro, predominantly at non-SQ/TQ sites, but this phosphorylation does
      not seem to affect the Rad3 action on Mrc1. Interestingly, the replication stress
      induced activation of Cds1 and hyperphosphorylation of Mrc1 is almost completely
      abrogated in an initiation-defective mutant of cdc45, but not in an mcm2 or
      polepsilon mutant. The results suggest that Hsk1-mediated loading of Cdc45 onto
      replication origins may play important roles in replication stress-induced
      checkpoint.

PMID- 21099361
TI  - Nek6 overexpression antagonizes p53-induced senescence in human cancer cells.
AB  - Nek6 is an NIMA-related kinase that plays a critical role in mitotic cell cycle
      progression. Recent studies have shown that Nek6 is upregulated in various human
      cancers, but the function of Nek6 in tumorigenesis is largely unknown. Here, we
      examined the role of Nek6 in cellular senescence. Our data revealed that Nek6
      expression is decreased both in both the replicative senescence of human normal
      fibroblasts and premature senescence induced by p53 expression in EJ human
      bladder cancer cells and H1299 human lung cancer cells. Interestingly, the
      enforced expression of Nek6 in EJ and H1299 cells completely suppresses p53
      induced senescence, whereas the expression of kinase-dead Nek6 did not affect p53
      induced senescence. Mechanistic studies revealed that cell cycle arrest in the G1
      and G2/M phases, as well as the reduction of cyclin B and cdc2 protein level upon
      p53 expression were significantly reduced by Nek6 overexpression. In addition,
      p53-induced increases in intracellular levels of ROS were also inhibited in cells
      overexpressing Nek6. These results suggest that the downregulation of Nek6
      expression is required for the onset of p53-induced cellular senescence and imply
      a possible role of Nek6 in tumorigenesis.

PMID- 21099363
TI  - ATRX: taming tandem repeats.

PMID- 21099362
TI  - Genetic interaction of RAD53 protein kinase with histones is important for DNA
      replication.
AB  - Studies in budding yeast suggest the protein kinase Rad53 plays novel roles in
      controlling initiation of DNA replication and in maintaining cellular histone
      levels, and these roles are independent of Rad53-mediated regulation of the
      checkpoint and of nucleotide levels. In order to elucidate the role of Rad53 in
      replication initiation, we isolated a novel allele of RAD53, rad53-rep, that
      separates the checkpoint function of RAD53 from the DNA replication function.
      rad53-rep mutants display a chromosome loss phenotype that is suppressed by
      increased origin dosage, providing further evidence that Rad53 plays a role in
      the initiation of DNA replication. Deletion of the major histone H3-H4 pair
      suppresses rad53-rep-cdc7-1 synthetic lethality, suggesting Rad53's functions in
      degradation of excess cellular histone and in replication initiation are related.
      Rad53-rep is active as a protein kinase yet fails to interact with origins of
      replication and like the rad53D mutant, the rad53-rep mutant accumulates excess
      soluble histones, and it is sensitive to histone dosage. In contrast, a
      checkpoint defective allele of RAD53 with mutations in both FHA domains, binds
      origins, and growth of a rad53-FHA mutant is unaffected by histone dosage. Based
      on these observations, we hypothesize that the origin binding and the histone
      degradation activities of Rad53 are central to its function in DNA replication
      and are independent of its checkpoint functions. We propose a model in which
      Rad53 acts as a "nucleosome buffer," interacting with origins of replication to
      prevent the binding of excess histones to origin DNA and to maintain proper
      chromatin configuration.

PMID- 21099364
TI  - Transcriptional and post-transcriptional mechanisms of BAFF-receptor
      dysregulation in human B lineage malignancies.
AB  - Together, circulating BAFF and dominant receptor BAFF-R homeostatically regulate
      the humoral immune system. Consistently aberrant BAFF-R expression in leukemic
      cells reveals an intimate connection of these cells' malignant physiology to the
      BAFF/BAFF-R axis and also provides an additional survival mechanism to the
      expressing cells. In this study, we used primary cells and cell lines to
      interrogate the mechanisms underlying aberrant BAFF-R expression in precursor B
      acute lymphoblastic leukemia (precursor B-ALL) and mature B chronic lymphocytic
      leukemia (CLL). Here we demonstrate the aberrant expression of BAFF-R in
      precursor B-ALL cell lines and reveal that these cells acquire BAFF-R expression
      through premature transcriptional activation of the BAFF-R promoter in
      coordination with regulatory transcription factor c-Rel. Investigations using
      primary CLL cells provide a crucial counterpoint through their paucity of BAFF-R
      relative to their benign mature B cell counterparts, which we establish as
      functionally significant in its depletion of the CLL cells' BAFF-binding
      capacity. Furthermore, BAFF-R downregulation in CLL patients is revealed here to
      be restricted to the malignant compartment and mediated post-transcriptionally in
      order to compensate for the consistently unchanged levels of transcription factor
      c-Rel and BAFF-R mRNA. Finally, we present evidence that CLL cells retain
      endogenous mechanisms of BAFF-R regulatory control despite active receptor
      dysregulation.

PMID- 21099365
TI  - The interacting domains of hCdt1 and hMcm6 involved in the chromatin loading of
      the MCM complex in human cells.
AB  - The stepwise assembly of pre-replicative complexes (pre-RCs) is essential for the
      initiation of DNA replication. Cdt1, a component of the pre-RC, is required for
      the loading of the minichromosome maintenance (MCM) complex onto chromatin. Cdt1
      physically interacts with the MCM complex, and this interaction mainly occurs
      between Cdt1 and Mcm6 in human cells. Here we show by yeast two-hybrid analysis,
      co-immunoprecipitation and GST pull-down assays that the extreme C-terminal
      region of hMcm6 (a.a. 708-821) interacts with a short C-terminal region in hCdt1
      (a.a. 392-471), while the large N-terminal part of hMcm6 (a.a. 1-707) interacts
      with some other MCM subunits. Furthermore, our functional studies show that
      ectopic expression of either of the interacting domains of hCdt1 and hMcm6 in
      human cells reduces chromatin association of the MCM complex and DNA replication,
      inhibits cell proliferation, and leads to cell apoptosis. These dominant negative
      effects indicate that the interaction between hCdt1 and hMcm6 through their
      interacting domains we identified is the key for hCdt1 in facilitating the MCM
      hetero-hexamer to load onto chromatin for replication licensing. The newly
      indentified interacting domains of hCdt1 and hMcm6 may become targets for
      identification of novel anticancer drugs.

PMID- 21099368
TI  - A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting
      and an antiTAG-72 antibody CC49.
AB  - The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires
      further validation in tumored mice before clinical trials. We now report on a
      therapeutic study in mice pretargeted with MORF-CC49 (an anti-TAG-72 antibody
      CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then
      targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose
      escalating therapeutic study, a pretargeting study in LS174T tumored mice was
      performed at tracer levels. By both necropsy and imaging, the tracer study showed
      that the whole body radioactivity was largely restricted to tumor in the mice
      pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained
      over 90 h. After decay correction, a best-fit to the biodistribution provided the
      areas under the radioactivity curves (AUCs) used for the radiation dose
      estimates. The tumor to normal organ AUC ratios in all cases were greater than
      unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in
      the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but
      temporary tumor remission was evident in 3 out of the 5 animals. Histological
      examination of tissues from these animals showed no evidence of cytotoxicity to
      normal tissues but obvious radiation damage to tumor. In conclusion, effective
      radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re
      as the therapeutic radionuclide and CC49 as the pretargeting antibody.

PMID- 21099366
TI  - The Nrf2 transcription factor is a positive regulator of myeloid differentiation
      of acute myeloid leukemia cells.
AB  - 1alpha,25-dihydroxyvitamin D3 (1,25D) is a powerful differentiation agent, which
      has potential for treatment of acute myeloid leukemia (AML), but induces severe
      hypercalcemia at pharmacologically active doses. We have previously shown that
      carnosic acid (CA), the polyphenolic antioxidant from rosemary plant, markedly
      potentiates differentiation induced by low concentrations of 1,25D in human AML
      cell lines. Here, we demonstrated similar enhanced differentiation responses to
      the 1,25D/CA combination in primary leukemic cells derived from patients with
      AML, and determined the role of the Nrf2/antioxidant response element (Nrf2/ARE)
      pathway in these effects using U937 human monoblastic leukemia cells as the
      model. CA strongly transactivated the ARE-luciferase reporter gene, induced the
      ARE-responsive genes, NADP(H)-quinone oxidoreductase and the gamma
      glutamylcysteine synthetase heavy subunit, and elevated cellular glutathione
      levels. Interestingly, 1,25D potentiated the effects of CA on these activities.
      Stable transfection of wild-type (wt) Nrf2 resulted in the enhancement, while
      transfection of dominant-negative (dn) Nrf2 produced suppression of
      differentiation induced by the 1,25D/CA combination and, surprisingly, by 1,25D
      alone. These opposite effects were associated with a corresponding increase or
      decrease in vitamin D receptor and retinoid X receptor-alpha protein levels, and
      in vitamin D responsive element transactivation. Cells transfected with wtNrf2
      and dnNrf2 also displayed opposing changes in the levels of the AP-1 family
      proteins (c-Jun and ATF2) and AP-1 transcriptional activity. Pretreatment with AP
      1 decoy oligodeoxynucleotide markedly attenuated the differentiation in wtNrf2
      transfected cells, suggesting that the pro-differentiation action of Nrf2 is
      mediated by functional AP-1. Our findings suggest that the Nrf2/ARE pathway plays
      an important part in the cooperative induction of myeloid leukemia cell
      differentiation by 1,25D and a plant polyphenol.

PMID- 21099370
TI  - Sequencing antibody repertoires: the next generation.
AB  - Genomic studies have been revolutionized by the use of next generation sequencing
      (NGS) that delivers huge amounts of sequence information in a short span of time.
      The number of applications for NGS is rapidly expanding and significantly
      transforming many areas of life sciences. The field of antibody research and
      discovery is no exception. Several recent studies have harnessed the power of NGS
      for analyzing natural or synthetic immunoglobulin repertoires with unprecedented
      resolution and exploring alternative paths for antibody discovery. Thus,
      appreciating, and then exploiting, these advances is essential for staying at the
      edge of antibody innovation.

PMID- 21099372
TI  - Can an enzyme cofactor be a factor in malignant progression?

PMID- 21099369
TI  - Targeting antibodies to the cytoplasm.
AB  - A growing number of research consortia are now focused on generating antibodies
      and recombinant antibody fragments that target the human proteome. A particularly
      valuable application for these binding molecules would be their use inside a
      living cell, e.g., for imaging or functional intervention. Animal-derived
      antibodies must be brought into the cell through the membrane, whereas the
      availability of the antibody genes from phage display systems allows
      intracellular expression. Here, the various technologies to target intracellular
      proteins with antibodies are reviewed.

PMID- 21099373
TI  - Identification of cancer stem cells in gallbladder carcinoma: a platform for the
      discovery of novel therapeutic targets.

PMID- 21099371
TI  - A fibronectin scaffold approach to bispecific inhibitors of epidermal growth
      factor receptor and insulin-like growth factor-I receptor.
AB  - Engineered domains of human fibronectin (AdnectinsTM) were used to generate a
      bispecific Adnectin targeting epidermal growth factor receptor (EGFR) and insulin
      like growth factor-I receptor (IGF-IR), two transmembrane receptors that mediate
      proliferative and survival cell signaling in cancer. Single-domain Adnectins that
      specifically bind EGFR or IGF-IR were generated using mRNA display with a library
      containing as many as 10 ( 13) Adnectin variants. mRNA display was also used to
      optimize lead Adnectin affinities, resulting in clones that inhibited EGFR
      phosphorylation at 7 to 38 nM compared to 2.6 MUM for the parental clone.
      Individual, optimized, Adnectins specific for blocking either EGFR or IGF-IR
      signaling were engineered into a single protein (EI-Tandem Adnectin). The EI
      Tandems inhibited phosphorylation of EGFR and IGF-IR, induced receptor
      degradation, and inhibited down-stream cell signaling and proliferation of human
      cancer cell lines (A431, H292, BxPC3 and RH41) with IC 50 values ranging from 0.1
      to 113 nM. Although Adnectins bound to EGFR at a site distinct from those of anti
      EGFR antibodies cetuximab, panitumumab and nimotuzumab, like the antibodies, the
      anti-EGFR Adnectins blocked the binding of EGF to EGFR. PEGylated EI-Tandem
      inhibited the growth of both EGFR and IGF-IR driven human tumor xenografts,
      induced degradation of EGFR, and reduced EGFR phosphorylation in tumors. These
      results demonstrate efficient engineering of bispecific Adnectins with high
      potency and desired specificity. The bispecificity may improve biological
      activity compared to monospecific biologics as tumor growth is driven by multiple
      growth factors. Our results illustrate a technological advancement for
      constructing multi-specific biologics in cancer therapy.

PMID- 21099375
TI  - The intimate relationship between catatonia and convulsive therapy.

PMID- 21099376
TI  - Catatonia in Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition.

PMID- 21099377
TI  - Electroconvulsive therapy in adolescents with the catatonia syndrome: efficacy
      and ethics.
AB  - OBJECTIVES: In child and adolescent psychiatry, catatonia is infrequent, but it
      is one of the most severe syndromes, characterized by the coexistence of psychic
      and motor symptoms. In this report, we explore the therapeutic experience with
      electroconvulsive therapy (ECT) in adolescents with catatonia. METHODS: We review
      the literature (1985-2009) to clarify issues related to the use of ECT in child
      and adolescent patients with catatonia. RESULTS: Electroconvulsive therapy is
      used as second-line management after high-dose benzodiazepine trials.
      Electroconvulsive therapy is an effective, safe, and useful procedure in the
      treatment of catatonic youngsters as reported in 59 patients. Ethical issues
      regarding the use of ECT are analyzed and their implications briefly discussed in
      the light of general medical ethics. CONCLUSIONS: Electroconvulsive therapy is a
      safe and effective treatment for catatonia in children and adolescents.

PMID- 21099378
TI  - Electroconvulsive therapy in a patient with Klippel-Trenaunay-Weber syndrome
      complicated by partial popliteal vein thrombosis.

PMID- 21099382
TI  - New access options at www.op-rs.com.

PMID- 21099383
TI  - Study on the effectiveness of antibiotic prophylaxis in external
      dacryocystorhinostomy: a review of 697 cases.
AB  - PURPOSE: To evaluate the prophylactic use of antibiotics in external
      dacryocystorhinostomy for the prevention of postoperative complications. METHODS:
      This study included 697 patients diagnosed with distal nasolacrimal duct
      obstruction and who were operated on by the same surgeon. Direct culture of the
      lacrimal sac content was carried out. Data were collected regarding clinical
      signs and symptoms, use of intraoperative antibiotics, results of culture samples
      obtained during surgery, and antibiogram analysis. Also, the postoperative period
      was analyzed with regard to the presence of postoperative complications. RESULTS:
      Out of 697 patients, 536 were women. The mean age at surgery was 67.0 +/- 13.3
      years. Prior to surgery, 19.5%, 18.5%, 11%, and 17.8% of patients showed
      recurrent conjunctivitis, mucocele, mucopyocele, and episodes of acute
      dacryocystitis, respectively. Seventy-three patients did not receive prophylactic
      treatment during surgery. A total of 8.3% of lacrimal sacs were culture positive,
      the most commonly isolated organism being Staphylococcus aureus. The use of
      antibiotics during surgery was not associated with a lower rate of postoperative
      complications. A statistically significant association was found between some
      clinical pictures, such as mucocele, mucopyocele, and dacryocystitis, and a
      higher rate of positive cultures. CONCLUSIONS: This study questions the
      generalized use of prophylactic antibiotics for external dacryocystorhinostomy,
      while providing evidence to indicate their use for patients who have had prior
      episodes of mucocele, mucopyocele, or acute dacryocystitis.

PMID- 21099384
TI  - Necrobiotic xanthogranuloma with predominant periorbital involvement.
AB  - We present an unusual variant of necrobiotic xanthogranuloma with periorbital
      involvement. Our patient had an unusually complicated course due to initial
      misdiagnosis and patient refusal to undergo treatment. We present her clinical
      course and review the literature on this rare lesion.

PMID- 21099385
TI  - Assessing student mental health at the Vanderbilt University School of Medicine.
AB  - PURPOSE: To determine the prevalence rates of four major categories of mental
      illness among medical students and to examine associations between these
      illnesses and a range of demographic variables. METHOD: The authors invited all
      330 first-, second-, and third-year medical students at Vanderbilt University
      School of Medicine to participate in a survey during winter 2008-2009. Students
      completed an anonymous written questionnaire assessing the prevalence of
      depression, anxiety, eating disorders, and alcohol and drug use disorders.
      Additionally, the authors obtained student demographic information to investigate
      variations in rates of illness based on interindividual differences. RESULTS:
      Most students (301; response rate: 91.2%) completed the survey. The authors found
      that depression and anxiety were more prevalent in the Vanderbilt medical student
      population than in their nonmedical peer group. The authors found that 37 (12%)
      of the students were borderline for possible alcohol abuse and 3 (1%) were
      problem drinkers, 1 (0.3%) had a possible drug abuse disorder, and 3 (1%) had
      possible eating disorders. Whereas exercising one to three times per week was
      associated with lower rates of both depression and anxiety, having a family
      history of mental illness was associated with higher eating disorder scores and
      anxiety. There was an association between gender and all disorders. CONCLUSIONS:
      Insight into the prevalence of mental health disorders in the medical student
      population and the variables that may influence them provides important
      information for medical schools as they develop more robust and effective
      wellness programs to help students in these very stressful learning environments.

PMID- 21099386
TI  - Supporting medical education research quality: the Association of American
      Medical Colleges' Medical Education Research Certificate program.
AB  - The quality of the medical education research (MER) reported in the literature
      has been frequently criticized. Numerous reasons have been provided for these
      shortcomings, including the level of research training and experience of many
      medical school faculty. The faculty development required to improve MER can take
      various forms. This article describes the Medical Education Research Certificate
      (MERC) program, a national faculty development program that focuses exclusively
      on MER. Sponsored by the Association of American Medical Colleges and led by a
      committee of established medical education researchers from across the United
      States, the MERC program is built on a set of 11 interactive workshops offered at
      various times and places across the United States. MERC participants can
      customize the program by selecting six workshops from this set to fulfill
      requirements for certification. This article describes the history, operations,
      current organization, and evaluation of the program. Key elements of the
      program's success include alignment of program content and focus with needs
      identified by prospective users, flexibility in program organization and
      logistics to fit participant schedules, an emphasis on practical application of
      MER principles in the context of the participants' activities and interests,
      consistency in program content and format to ensure standards of quality, and a
      sustainable financial model. The relationship between the national MERC program
      and local faculty development initiatives is also described. The success of the
      MERC program suggests that it may be a possible model for nationally disseminated
      faculty development programs in other domains.

PMID- 21099387
TI  - Perspective: Recognizing and rewarding clinical scholarship.
AB  - Faculty members in medical schools and academic medical centers are in a constant
      process of generating new knowledge. The cornerstone of academia--and academic
      medicine--is scholarship. Traditionally, tenure and/or academic promotion in the
      professorial ranks is awarded to those who meet institutional criteria in the
      missions of research, teaching, and service, including patient care. In the
      academic review process, priority is often placed on a record of demonstrated,
      consistent success in traditional laboratory research, also known as the
      scholarship of discovery. More recently, there has been greater recognition of
      other forms of scholarship: education, application, and integration. These forms
      of scholarship, although less recognized, also result in the generation of new
      knowledge. In an attempt to understand the breadth and scope of clinical
      scholarship, the authors searched the extant literature in academic medicine for
      a definition of clinical scholarship and expanded the search to disciplines
      outside of medicine. They found that succinct, discrete definitions of clinical
      scholarship have been published in other disciplines, but not in academic
      medicine. After reviewing definitions of clinical scholarship from other
      disciplines, adapting definitions of educational scholarship in academic
      medicine, and including qualities unique to clinical scholarship, the authors
      developed a framework for understanding clinical scholarship in academic medicine
      as a means for opening a dialogue within the academic medical community. This
      dialogue hopefully will lead to formulating a succinct, discrete definition of
      clinical scholarship that will allow greater recognition and reward for clinical
      scholars in the promotion and tenure process.

PMID- 21099388
TI  - Are United States Medical Licensing Exam Step 1 and 2 scores valid measures for
      postgraduate medical residency selection decisions?
AB  - PURPOSE: United States Medical Licensing Examination (USMLE) scores are
      frequently used by residency program directors when evaluating applicants. The
      objectives of this report are to study the chain of reasoning and evidence that
      underlies the use of USMLE Step 1 and 2 scores for postgraduate medical resident
      selection decisions and to evaluate the validity argument about the utility of
      USMLE scores for this purpose. METHOD: This is a research synthesis using the
      critical review approach. The study first describes the chain of reasoning that
      underlies a validity argument about using test scores for a specific purpose. It
      continues by summarizing correlations of USMLE Step 1 and 2 scores and reliable
      measures of clinical skill acquisition drawn from nine studies involving 393
      medical learners from 2005 to 2010. The integrity of the validity argument about
      using USMLE Step 1 and 2 scores for postgraduate residency selection decisions is
      tested. RESULTS: The research synthesis shows that USMLE Step 1 and 2 scores are
      not correlated with reliable measures of medical students', residents', and
      fellows' clinical skill acquisition. CONCLUSIONS: The validity argument about
      using USMLE Step 1 and 2 scores for postgraduate residency selection decisions is
      neither structured, coherent, nor evidence based. The USMLE score validity
      argument breaks down on grounds of extrapolation and decision/interpretation
      because the scores are not associated with measures of clinical skill acquisition
      among advanced medical students, residents, and subspecialty fellows. Continued
      use of USMLE Step 1 and 2 scores for postgraduate medical residency selection
      decisions is discouraged.

PMID- 21099389
TI  - Do students' and authors' genders affect evaluations? A linguistic analysis of
      Medical Student Performance Evaluations.
AB  - PURPOSE: Recent guidelines for the Medical Student Performance Evaluation (MSPE)
      have standardized the "dean's letter." The authors examined MSPEs for linguistic
      differences according to student or author gender. METHOD: This 2009 study
      analyzed 297 MSPEs for 227 male and 70 female medical students applying to a
      diagnostic radiology residency program. Text analysis software identified word
      counts, categories, frequencies, and contexts; factor analysis detected patterns
      of word categories in student-author gender pairings. RESULTS: Analyses showed a
      main effect for student gender (P=.046) and a group difference for the author
      student gender combinations (P=.048). Female authors of male student MSPEs used
      the fewest "positive emotion" words (P=.006). MSPEs by male authors were shorter
      than those by females (P=.014). MSPEs for students ranked in the National
      Resident Matching Program contained more "standout" (P=.002) and "positive
      emotion" (P=.001) words. There were no differences in the author-gender pairs in
      the proportion of students ranked, although predominant word categories differed
      by author and student gender. Factor analysis revealed differences among the
      author-student groups in patterns of correlations among word categories.
      CONCLUSIONS: MSPEs differed slightly but significantly by student and author
      gender. These differences may derive from societal norms for male and female
      behaviors and the subsequent linguistic interpretation of these behaviors, which
      itself may be colored by the observer's gender. Although the differences in MSPEs
      did not seem to influence students' rankings, this work underscores the need for
      awareness of the complex effects of gender in evaluating students and guiding
      their specialty choices.

PMID- 21099390
TI  - Gender differences in academic productivity and leadership appointments of
      physicians throughout academic careers.
AB  - PURPOSE: Because those selected for leadership in academic medicine often have a
      record of academic productivity, publication disparities may help explain the
      gender imbalance in leadership roles. The authors aimed to compare the
      publication records, academic promotions, and leadership appointments of women
      and men physicians longitudinally throughout academic careers. METHOD: In 2007,
      the authors conducted a retrospective, longitudinal cohort study of all 25 women
      physicians then employed at Mayo Clinic with >=20 years of service at Mayo and of
      50 male physician controls, matched 2:1 by appointment date and career category,
      to women. The authors recorded peer-reviewed publications, timing of promotion,
      and leadership appointments throughout their careers. RESULTS: Women published
      fewer articles throughout their careers than men (mean [standard deviation] 29.5
      [28.8] versus 75.8 [60.3], P = .001). However, after 27 years, women produced a
      mean of 1.57 more publications annually than men (P < .001). Thirty-three men
      (66%) achieved an academic rank of professor compared with seven women (28%) (P =
      .01). Throughout their careers, women held fewer leadership roles than men (P <
      .001). Nearly half (no. = 11; 44%) of women attained no leadership position,
      compared with 15 men (30%). CONCLUSIONS: Women's publication rates increase and
      actually exceed those of men in the latter stages of careers, yet women hold
      fewer leadership positions than men overall, suggesting that academic
      productivity assessed midcareer may not be an appropriate measure of leadership
      skills and that factors other than publication record and academic rank should be
      considered in selecting leaders.

PMID- 21099391
TI  - Developing a "frequent look and rapid remediation" assessment system for a new
      medical school.
AB  - The Peninsula College of Medicine and Dentistry (PCMD) was among the five new
      medical schools approved in the United Kingdom in 2000. PCMD required a new
      curriculum and a new outcomes-oriented assessment system based on sound
      educational theory. The resulting system was designed to use multiple sampling
      and show increasing authenticity as students progress through the curriculum. A
      "frequent look and rapid remediation" structure was incorporated to allow faculty
      to evaluate student competence throughout the year and take immediate action when
      warranted. Using a recently published framework, the authors retrospectively
      evaluate the assessment system and share many of the decisions they and their
      colleagues had to make. They discuss how to support stakeholders in understanding
      and contributing to the development of an assessment system and how to meet some
      of the challenges they encountered. They consider indicators of success in terms
      of the performance of the assessment system as a whole and the ways the system
      contributes to educational research. They suggest that future research should
      focus on building greater flexibility into the system so that assessment
      decisions can be individualized to particular students.

PMID- 21099392
TI  - Use of simulated pages to prepare medical students for internship and improve
      patient safety.
AB  - PURPOSE: During the transition from medical school to internship, trainees
      experience high levels of stress related to pages on the inpatient wards. The
      steep learning curve during this period may also affect patient safety. The
      authors piloted the use of simulated pages to improve medical student
      preparedness, decrease stress related to pages, and familiarize medical students
      with common patient problems. METHOD: A multidisciplinary team at Southern
      Illinois University School of Medicine developed simulated pages that were tested
      among senior medical students. Sixteen medical students were presented with 11
      common patient scenarios. Data on assessment, management, and global performance
      were collected. Mean confidence levels were evaluated pre- and postintervention.
      Students were also surveyed on how the simulated pages program influenced their
      perceived comfort in managing patient care needs and the usefulness of the
      exercise in preparing them to handle inpatient pages. RESULTS: Mean scores on the
      assessment and management portions of the scenarios varied widely depending on
      the scenario (range -15.6 +/- 41.6 to 95.7 +/- 9.5). Pass rates based on global
      performance ranged from 12% to 93%. Interrater agreement was high (mean kappa =
      0.88). Students' confidence ratings on a six-point scale increased from 1.87
      preintervention to 3.53 postintervention (P < .0001). CONCLUSIONS: Simulated
      pages engage medical students and may foster medical student preparedness for
      internship. Students valued the opportunity to simulate "on call"
      responsibilities, and exposure to simulated pages significantly increased their
      confidence levels. Further studies are needed to determine effects on patient
      safety outcomes.

PMID- 21099393
TI  - Regulation of medical student work hours: a national survey of deans.
AB  - PURPOSE: Because of the impact of resident duty hours on resident and medical
      student education, it is important to determine curriculum deans' opinions toward
      and current status of student work hours regulations. METHOD: In 2008, the
      authors electronically surveyed the curriculum deans at the 126 U.S. medical
      schools accredited by the Liaison Committee on Medical Education (LCME) regarding
      student work hours at their schools. RESULTS: Sixty-six respondents (82%) had a
      written policy restricting their students' work hours, and in 63% of these, the
      policy also extended to students visiting their institution. Policies applied to
      mandatory and elective (84%) or only mandatory (16%) rotations. About half the
      respondents supported a universal policy across medical schools, but of those who
      supported a policy, there was an equal split between whether individual schools
      or the LCME should create the policy. Deans felt strongly (>80%) that student
      well-being would be improved by work hours regulation, yet 48% noted that it
      would negatively affect scheduling required clerkship activities. Fifty-four
      percent supported the Accreditation Council for Graduate Medical Education work
      hours policy for students, and most (82%) felt that students should work no more
      than 80 hours/week. Students are always supervised, yet extended work hours can
      affect learning and patient and team interactions. CONCLUSIONS: Without a
      mandate, many schools have created policies to restrict student work hours. This
      study describes the current status and offers an opportunity for consensus
      building around this important issue.

PMID- 21099394
TI  - The third year in the first person: medical students report on their principal
      clinical year.
AB  - PURPOSE: To obtain an accurate and detailed portrait of medical students'
      principal clinical year using firsthand accounts of their experiences over the
      course of the year. METHOD: All 45 Harvard Medical School students at four
      clinical sites who were training in 2005-2006 under three different pedagogical
      models provided open-ended responses to a monthly check-in asking them for brief
      descriptions of any interesting or memorable experiences associated with their
      clerkships. Associations with gender, time of year, rotation, and clerkship model
      were also studied. RESULTS: A total of 770 incidents were collected, and these
      were coded for positivity-negativity and content. Five broad theme areas were
      identified: stories about physicians (e.g., physicians giving instruction, acting
      as role models), medical students and their behavior (feelings of uncertainty or
      being useful, of workload), patients and patient care (e.g., learning by doing or
      observing, forming bonds with patients, memorable patients, treating patients
      over time), groups and group climate (e.g., effectiveness of teams, informal
      groups, comparison of services), and content themes (e.g., birth, death, cancer,
      bad news). Two-thirds of all stories were coded as positive. CONCLUSIONS: These
      third-year medical students often framed their experiences positively, finding
      learning lessons even in stressful or unpleasant events. Their stories also
      reflect relatively consistent orientations toward patients and patient care
      (e.g., biomedical versus patient-centered). The authors believe these incidents
      reflect the emerging professional identities of medical students; educators can
      use these to help students reflect on the kind of physician they aspire to
      become.

PMID- 21099395
TI  - Undergraduate medical education in substance abuse: a review of the quality of
      the literature.
AB  - PURPOSE: To prepare to develop a medical school curriculum on substance abuse
      disorders (SADs), the authors conducted a review of the quality of the sparse
      published literature. METHOD: The authors searched MEDLINE (1950 through December
      2008) using OVID, PsycINFO, and PubMed to identify all studies of SAD
      interventions targeted toward undergraduate medical students. Of the 1,084
      studies identified initially, 31 reported sufficient data to allow the authors to
      evaluate quality using Medical Education Research Study Quality Instrument
      (MERSQI) scores. The authors also determined the impact of the studies by
      considering three-year citation rate and journal impact factor. A detailed review
      of the literature provided data on contact hours and intervention content.
      RESULTS: The three-rater intraclass correlation coefficient for total MERSQI
      score was 0.82 (95% confidence interval: 0.70-0.90). The mean MERSQI score was
      10.42 of a possible 18 (SD 2.59; range: 6.33-14.83). MERSQI scores were higher
      for more recently published studies and correlated with three-year citation rate
      but not impact factor. The mean contact time for 26 studies was 29.25 hours
      (range: 0.83-200 hours). CONCLUSIONS: The literature provides a variety of
      educational methods to train medical students in SAD detection and intervention
      skills. This literature is of variable quality and provides limited guidance for
      development of curricula and medical education policy. Better methods of
      curriculum evaluation and publication guidelines would help ensure that this
      literature has a positive impact on educational practice and public health.

PMID- 21099396
TI  - Factors that influence general internists' and surgeons' performance on
      maintenance of certification exams.
AB  - PURPOSE: Good clinical judgment is important to providing high-quality patient
      care. Keeping current in one's field is challenged by rapid advances in health
      care and demanding practices. Understanding the collective factors that influence
      a practicing physician's clinical judgment could help medical educators design
      improvement programs that target specific audiences. METHOD: Data from two
      medical specialty boards, the American Board of Internal Medicine and American
      Board of Surgery, were used. Multiple regression analyses were conducted relating
      first-attempt performance on the maintenance of certification (MOC) exam with
      physician age, amount of continuing medical education (CME) undertaken, number of
      physicians in the practice, medical school type, and prior exam performance. Data
      were based on demographics and exam scores of 18,447 general internists and 4,961
      general surgeons who took the MOC exam for the first time between 2003 and 2007.
      RESULTS: Similar findings were obtained for general internists and surgeons.
      Younger physicians, those with higher scores on initial certification, physicians
      in group not solo practice, and U.S. medical graduates were significantly more
      likely to pass the MOC exam (P<.001). Effect sizes were small except for
      performance on the initial certification exam. General internists with higher
      internal medicine program directors' ratings and more CME activities were also
      significantly more likely to pass (P<.001). CONCLUSIONS: Medical educators may
      target improvement programs for those who practice in isolation, are older, are
      international medical graduates, and performed poorly on their initial
      certification exam. Practicing without sustaining requisite clinical judgment has
      serious implications for patient care.

PMID- 21099397
TI  - Three innovative curricula for addressing medical students' career development.
AB  - Medical students make specialty decisions that are critically important to their
      long-term career satisfaction and overall well-being. The dynamic of larger class
      sizes set against stagnant numbers of residency positions creates an imperative
      for students to make and test specialty decisions earlier in medical school.
      Ideally, formal career advising begins in medical school. Medical schools
      typically offer career development programs as extracurricular offerings. The
      authors describe three curricular approaches and the innovative courses developed
      to address medical students' career development needs. The models differ in
      complexity and cost, but they share the goals of assisting students to form
      career identities and to use resources effectively in their specialty decision
      processes. The first model is a student-organized specialties elective. To earn
      course credit, students must complete questionnaires for the sessions, submit
      results from two self-assessments, and report on two physician informational
      interviews. The second model comprises two second-year career development courses
      that have evolved into a longitudinal career development program. The third model
      integrates career topics through a doctoring course and advising teams. The
      authors discuss challenges and lessons learned from implementing each of the
      programs, including marshaling resources, achieving student buy-in, and obtaining
      time in the curriculum. Invoking a curricular approach seems to normalize the
      tasks associated with career development and puts them on par in importance with
      other medical school endeavors.

PMID- 21099398
TI  - Qualitative analysis of medical student impressions of a narrative exercise in
      the third-year psychiatry clerkship.
AB  - PURPOSE: Clinical clerkship directors and faculty undertake the challenge of
      teaching patient-centered communication to students who face the enormous doctor
      centered task of learning diagnostic medicine. The authors examined students'
      written reactions to the narrative exercise, which, drawing from narrative
      medicine and narrative therapy, challenges students to be more patient-centered
      by writing a patient's life story and sharing it with that patient. METHOD:
      During one-half of an academic year (2008-2009), the authors used qualitative
      methods to explore the range of medical student experiences with the narrative
      exercise in the psychiatry clerkship. RESULTS: During the study period, 46
      medical students completed the exercise, and 44 (96%) submitted 367 comments for
      the research team to analyze. Four broad categories emerged: (1) communication,
      (2) insight, (3) hope, and (4) mixed or negative reactions. The most common theme
      was improved communication, which comprised the subcategories of enhanced active
      listening, opening up, and relationship building. Improved insights included
      student insights into their patients, as well as the facilitation of patient
      insights into themselves, especially regarding their own strengths and
      relationships. The exercise was well received by students: Only five comments
      were categorized as negative, and all of these related to difficulties selecting
      patients. CONCLUSIONS: Students reported many examples of improved patient
      centered communication facilitated by the exercise. The narrative exercise may
      also promote a greater understanding of patients as complete human beings rather
      than diagnostic entities. The approach may be useful in educational settings
      beyond the psychiatry clerkship.

PMID- 21099399
TI  - Do e-mail alerts of new research increase knowledge translation? A "Nephrology
      Now" randomized control trial.
AB  - PURPOSE: As the volume of medical literature increases exponentially, maintaining
      current clinical practice is becoming more difficult. Multiple, Internet-based
      journal clubs and alert services have recently emerged. The purpose of this study
      is to determine whether the use of the e-mail alert service, Nephrology Now,
      increases knowledge translation regarding current nephrology literature. METHOD:
      Nephrology Now is a nonprofit, monthly e-mail alert service that highlights
      clinically relevant articles in nephrology. In 2007-2008, the authors randomized
      1,683 subscribers into two different groups receiving select intervention
      articles, and then they used an online survey to assess both groups on their
      familiarity with the articles and their acquisition of knowledge. RESULTS: Of the
      randomized subscribers, 803 (47.7%) completed surveys, and the two groups had a
      similar number of responses (401 and 402, respectively). The authors noted no
      differences in baseline characteristics between the two groups. Familiarity
      increased as a result of the Nephrology Now alerts (0.23 +/- 0.087 units on a
      familiarity scale; 95% confidence interval [CI]: 0.06-0.41; P = .007) especially
      in physicians (multivariate odds ratio 1.83; P = .0002). No detectable
      improvement in knowledge occurred (0.03 +/- 0.083 units on a knowledge scale; 95%
      CI: -0.13 to 0.20; P = .687). CONCLUSIONS: An e-mail alert service of new
      literature improved a component of knowledge translation--familiarity--but not
      knowledge acquisition in a large, randomized, international population.

PMID- 21099400
TI  - Behavioral momentum and relapse of ethanol seeking:  nondrug reinforcement in a
      context increases relative reinstatement.
AB  - Drug-related stimuli seem to contribute to the persistence of drug seeking and
      relapse. Behavioral momentum theory is a framework for understanding how the
      discriminative-stimulus context in which operant behavior occurs governs the
      persistence of that behavior. The theory suggests that both resistance to change
      and relapse are governed by the Pavlovian stimulus-reinforcer relation between a
      stimulus context and all sources of reinforcement obtained in that context. This
      experiment examined the role of the Pavlovian stimulus-reinforcer relation in
      reinstatement of ethanol seeking of rats by including added response-independent
      nondrug reinforcement in the self-administration context. Although rates of
      ethanol-maintained responding were lower in a context with added nondrug
      reinforcement than a context with ethanol alone, relative resistance to
      extinction and relative reinstatement were greater in the context previously
      associated with the nondrug reinforcer. Thus, both relative resistance to
      extinction and relative relapse of ethanol seeking depended on the Pavlovian
      stimulus-reinforcer relation between a context and all sources of reinforcement
      in that context. These findings suggest that to understand how drug-related
      contexts contribute to relapse, it may be necessary to consider not only the
      history of drug reinforcement in a context, but also the wide variety of other
      reinforcers obtained in such contexts.

PMID- 21099401
TI  - Cat-scratch uveitis confirmed by histological, serological, and molecular
      diagnoses.
AB  - PURPOSE: To report a case of a cat-scratch uveitis caused by Bartonella henselae,
      which was confirmed by histology, serology, and polymerase chain reaction (PCR)
      methodology. METHODS: An iris nodule was biopsied from a 4-year-old child who was
      scratched by a kitten on the side of his face and developed redness of the eye
      associated with cervical lymphadenopathy. Sections of the iridectomy specimen
      were stained with hematoxylin-eosin, periodic acid-Schiff, and Warthin-Starry
      technique for histopathologic evaluation. Additionally, serologic tests and
      molecular diagnosis using B. henselae-specific PCR were performed. RESULTS:
      Histopathologically, sections of the iridectomy specimen showed a zonal
      granulomatous inflammation with a central iris necrotic abscess surrounded by a
      mantle of epithelioid histiocytes and more peripherally by lymphocytes and plasma
      cells. The Warthin-Starry stain disclosed scattered short bacilli within the
      necrotic abscess morphologically compatible with B. henselae. Report of serologic
      tests for B. henselae disclosed a negative immunoglobulin G antibody (negative:
      less than 12) and a positive immunoglobulin M antibody of 18 (positive: greater
      than 15). Other serologic studies including Toxocara, histoplasmin, blastomycin,
      coccidioidin, aspergillin, and Chlamydia were all negative. PCR was positive for
      B. henselae DNA. CONCLUSIONS: Our case showed a unilateral chronic granulomatous
      iritis with the histopathologic features compatible with CSD caused by B.
      henselae bacillus as demonstrated in the iris biopsy and confirmed by serology
      and PCR technique. This case is an example of a relatively rare uveal
      manifestation of CSD.

PMID- 21099402
TI  - Isolated corneal papilloma-like lesion associated with human papilloma virus type
      6.
AB  - PURPOSE: To report a case of a corneal papilloma-like lesion associated with
      human papilloma virus type 6. METHODS: A 48-year-old woman presented with a 2
      year history of ocular discomfort and gradual visual deterioration in her right
      eye. Ophthalmic examination revealed an elevated, semitranslucent, well-defined
      vascularized mass approximately 4 * 2.5 mm in size localized to the right cornea.
      The surface of the mass appeared smooth and many small, shallow, and irregular
      elevations were noted. RESULTS: An excisional biopsy was performed. The
      underlying cornea was markedly thinned, and fine ramifying vasculature was also
      noted on the exposed corneal stroma. Typical koilocytic change was observed on
      the histopathologic examination. Polymerase chain reaction revealed the existence
      of human papilloma virus type 6 DNA. CONCLUSIONS: Here we describe a case of an
      isolated corneal papilloma-like lesion. Although the corneal extension of the
      limbal or the conjunctival papillomas has been commonly observed, an isolated
      corneal papilloma-like lesion with underlying stromal destruction has only rarely
      been reported.

PMID- 21099403
TI  - Herpes keratitis in a patient undergoing treatment with topical mitomycin C.
AB  - PURPOSE: To report a case of herpetic keratitis in a patient undergoing mitomycin
      C therapy for conjunctival squamous cell carcinoma. METHOD: Case report. RESULTS:
      A 70-year-old man was referred to the Massachusetts Eye Research and Surgery
      Institution in consultation for a persistent redness in the right eye. He was
      diagnosed with conjunctival squamous cell carcinoma and treated with topical
      mitomycin C (MMC). The patient initially improved on topical MMC therapy. At the
      end of the second cycle of topical MMC, he complained of intense ocular pain and
      redness in the eye under treatment. A diagnosis of herpetic epithelial keratitis
      was made based on the clinical findings, and he was subsequently treated with 1
      drop of trifluridine 9 times per day in the affected eye. The patient responded
      with dramatic improvement and resolution of symptoms. CONCLUSIONS: This case
      reports a reactivation of latent herpes simplex virus with productive ocular
      infection, triggered by MMC therapy and highlights the importance of awareness of
      this possible risk associated with the use of MMC.

PMID- 21099405
TI  - Retrospective review of graft dislocation rate associated with descemet stripping
      automated endothelial keratoplasty after primary failed penetrating keratoplasty.
AB  - PURPOSE: To report the rate of graft dislocation in patients who underwent
      Descemet stripping automated endothelial keratoplasty (DSAEK) after a previous
      penetrating keratoplasty (PKP). METHODS: Institutional review board-approved,
      multicenter, retrospective chart review. Inclusion criteria included: prior
      failed PKP and subsequent DSAEK. The primary outcomes measured in this study were
      the presence of a graft dislocation, rate of rebubble, and graft attachment.
      Additional variables included: presence of a prior glaucoma drainage device,
      graft-to-host size disparity, number of sutures remaining in PKP, and stripping
      of the Descemet membrane at the time of DSAEK surgery. RESULTS: Ninety patients
      (97 eyes) were included in the study. In 31% (30 of 97), the endothelial graft
      dislocated after surgery. All 30 cases required a rebubble except 1, which
      reattached spontaneously. Ninety-eight percent (95 of 97) of all grafts remained
      attached for the duration of the follow-up period. Only 2 eyes (2.2%) required
      repeat graft. Endothelial grafts dislocated in 67% of patients with glaucoma
      draining devices. The dislocation rate for grafts larger than the host was 12 of
      49 (24%), equal to the host was 3 of 17 (18%), and smaller than the host was 8 of
      19 (42%). Dislocations occurred in 5 of 21 (24%) of grafts with sutures remaining
      and 22 of 76 (29%) of those with all sutures out. Five of 12 (42%) cases of
      grafts performed without stripping the Descemet had dislocations. CONCLUSIONS:
      The graft dislocation rate in DSAEK procedures after PKP is comparable to that
      after primary DSAEK cases. Donor grafts that are smaller than the host PKP and
      the presence of prior glaucoma drainage devices are risk factors for higher rates
      of graft dislocation.

PMID- 21099404
TI  - Modulating endogenous electric currents in human corneal wounds--a novel approach
      of bioelectric stimulation without electrodes.
AB  - PURPOSE: To measure electric current in human corneal wounds and test the
      feasibility of pharmacologically enhancing the current to promote corneal wound
      healing. METHODS: Using a noninvasive vibrating probe, corneal electric current
      was measured before and after wounding of the epithelium of donated postmortem
      human corneas. The effects of drug aminophylline and chloride-free solution on
      wound current were also tested. RESULTS: Unwounded cornea had small outward
      currents (0.07 MUA/cm2). Wounding increased the current more than 5 fold (0.41
      MUA/cm2). Monitoring the wound current over time showed that it seemed to be
      actively regulated and maintained above normal unwounded levels for at least 6
      hours. The time course was similar to that previously measured in rat cornea.
      Drug treatment or chloride-free solution more than doubled the size of wound
      currents. CONCLUSIONS: Electric current at human corneal wounds can be
      significantly increased with aminophylline or chloride-free solution. Because
      corneal wound current directly correlates with wound healing rate, our results
      suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing
      of damaged cornea in patients with reduced wound healing such as the elderly or
      diabetic patient. This novel approach offers bioelectric stimulation without
      electrodes and can be readily tested in patients.

PMID- 21099406
TI  - Isolation of Kingella denitrificans from a corneal ulcer.
AB  - PURPOSE: To report a case of a corneal ulcer caused by an unusual pathogen.
      DESIGN: Case report. METHODS: Clinical review describing initial presentation,
      course, and outcome of 1 patient with a corneal ulcer caused by Kingella
      denitrificans. RESULTS: A 77-year-old man with a prior history of 4 penetrating
      keratoplasties in the right eye for herpes simplex virus keratitis presented with
      a 3-day history of a red painful right eye. On examination, he was found to have
      a corneal ulcer identified by culture as K. denitrificans. CONCLUSIONS: Although
      Kingella spp. is not a common ocular pathogen, it can infect the cornea,
      especially when the host immune defense is altered.

PMID- 21099407
TI  - Xenotransplantation--the future of corneal transplantation?
AB  - Although corneal transplantation (Tx) is readily available in the United States
      and certain other regions of the developed world, the need for human donor
      corneas worldwide far exceeds supply. There is currently renewed interest in the
      possibility of using corneas from other species, especially pigs, for Tx into
      humans (xeno-Tx). The biomechanical properties of human and pig corneas are
      similar. Studies in animal models of corneal xeno-Tx have documented both humoral
      and cellular immune responses that play roles in xenograft rejection. The results
      obtained from the Tx of corneas from wild-type (ie, genetically unmodified) pigs
      into nonhuman primates have been surprisingly good and encouraging. Recent
      progress in the genetic manipulation of pigs has led to the prospect that the
      remaining immunological barriers will be overcome. There is every reason for
      optimism that corneal xeno-Tx will become a clinical reality within the next few
      years.

PMID- 21099408
TI  - Bee sting of the cornea and conjunctiva: management and outcomes.
AB  - PURPOSE: To present the clinical features, management, and outcomes of 4 cases of
      bee sting injury to the cornea and conjunctiva. METHODS: Clinical features,
      external photographs, treatment, and outcomes of 4 cases of ocular bee stings are
      presented. RESULTS: In 3 cases, the stinger of the bee was retained on the
      cornea, and in 1 case, it was retained on the conjunctiva. One of the 3 corneal
      sting patients was stung on the laser in situ keratomileusis flap margin, which
      resulted in a partial tear of the flap. Retained bee stings were removed
      immediately in all 4 cases, and topical antibiotics were applied with adjuvant
      treatment. All patients had good visual outcomes without severe complications at
      follow-up. CONCLUSIONS: Ocular surface bee stings with retained stingers are
      rarely reported. A potential triad of penetrating, immunologic, and toxic injury
      must be taken into consideration. Vision can be restored by early removal of the
      sting and topical medication.

PMID- 21099409
TI  - A case report of doxycycline-induced Stevens-Johnson syndrome.
AB  - PURPOSE: To report the clinical findings of a case of Stevens-Johnson syndrome
      (SJS) precipitated by the use of systemic doxycycline. METHODS: Case report.
      RESULTS: A 49-year-old man developed SJS with ocular involvement after
      doxycycline use for respiratory symptoms. The patient developed persistent 2+
      conjunctival injection and foreshortening of the conjunctival fornices in both
      eyes. The right eye had a 3 * 3.4 mm corneal epithelial defect with 50% thinning.
      The left eye had a 2.6 * 3 mm corneal ulcer with a central perforation and a flat
      anterior chamber with 360 degrees of iridocorneal touch. CONCLUSIONS: This case
      illustrates the unusual presentation of SJS induced by doxycycline. The prevalent
      use of systemic doxycycline in the practice of ophthalmology for eyelid-related
      and ocular surface disorders coupled with the detrimental long-term sequelae of
      SJS renders a careful reevaluation for alternatives.

PMID- 21099410
TI  - Keratitis and corneal melt with ketorolac tromethamine after conductive
      keratoplasty.
AB  - PURPOSE: To report a case of keratitis and corneal melt after conductive
      keratoplasty (CK) enhancement. METHOD: Case report. RESULTS: A 52-year-old woman
      with emmetropic presbyopia had undergone previous CK for monovision and underwent
      CK enhancement 4 years later. Postoperatively, she was managed with ketorolac
      tromethamine 0.4% and developed keratitis and corneal melt. CONCLUSIONS: This is
      the first reported case of keratitis and corneal melt associated with
      nonsteroidal antiinflammatory topical medications in a post-CK patient.

PMID- 21099412
TI  - Prospective study of visual outcomes and endothelial survival with Descemet
      membrane automated endothelial keratoplasty.
AB  - PURPOSE: To evaluate vision and endothelial cell survival in an initial Descemet
      membrane automated endothelial keratoplasty (DMAEK) series. METHODS: This was a
      prospective nonrandomized study of an initial consecutive series of 40 DMAEK
      cases, performed with or without concomitant phacoemulsification and intraocular
      lens implantation. The graft was dissected with a microkeratome. A central 6- to
      7-mm big bubble was created to separate endothelium from stroma, and the
      overlying stroma was excised. The graft was cut to 8.5- to 9.5-mm diameter and
      inserted with a pull through technique. Eyes were treated for Fuchs endothelial
      dystrophy, secondary corneal decompensation, or previous failed endothelial
      transplant. Best spectacle-corrected visual acuity, manifest refraction,
      pachymetry, and endothelial cell density were assessed. RESULTS: Median best
      spectacle-corrected visual acuity was 20/30 at 1 month (range: 20/15-20/50),
      improved from 20/40 (range: 20/25-20/400) preoperatively, excluding 7 eyes (18%)
      with significant retinal pathology. Rates of 20/20, 20/25, 20/30, and 20/40
      vision were 25%, 71%, 89%, and 100%, respectively, at 3 months and 48%, 74%, 93%,
      and 100%, respectively, at 6 months. Median endothelial cell loss relative to
      baseline donor cell density was 31% at 6 months. Air was reinjected in 10 eyes
      (25%) to promote graft attachment, and 2 grafts (5%) failed to clear.
      CONCLUSIONS: DMAEK provided significant improvement in visual acuity and marked
      reduction in central corneal thickness. DMAEK had a higher rate of postoperative
      air reinjection than Descemet stripping endothelial keratoplasty and comparable 6
      month endothelial cell loss.

PMID- 21099413
TI  - Subconjunctival injections and povidone-iodine washings for the treatment of
      giant fornix syndrome.
AB  - PURPOSE: Giant fornix syndrome is a chronic copiously purulent conjunctivitis
      seen in elderly patients with dehiscence of the levator palpebrae superioris
      aponeurosis. We report a case of giant fornix syndrome secondary to methicillin
      resistant Staphylococcus aureus conjunctivitis that was recalcitrant to standard
      treatment modalities, and we describe 2 novel interventions for this condition,
      which succeeded in eradicating the infection. METHODS: Case report. RESULTS:
      After failing an aggressive treatment course of topical antibiotics and
      corticosteroids and after demonstrating an inability to tolerate oral
      antibiotics, the patient was treated with supratarsal subconjunctival injections
      of vancomycin and triamcinolone, followed by repeated sweepings of the
      conjunctival fornices with 10% povidone-iodine on a cotton swab. The patient's
      symptoms improved dramatically after the antibiotic and corticosteroid injections
      and ultimately resolved completely after multiple povidone-iodine sweepings.
      CONCLUSIONS: In patients with giant fornix syndrome who are recalcitrant to or
      intolerant of aggressive topical and systemic therapy, supratarsal
      subconjunctival injections of antibiotics and corticosteroids and sweeping of the
      conjunctival fornices with povidone-iodine are 2 local treatments which may be
      useful in eradicating the infection.

PMID- 21099414
TI  - Phakic descemet stripping automated endothelial keratoplasty: prevalence and
      prognostic impact of postoperative cataracts.
AB  - PURPOSE: To determine the prevalence and risk factors for the development of
      visually significant cataracts after phakic Descemet stripping automated
      endothelial keratoplasty (DSAEK) and the impact of this complication on the final
      outcome. METHODS: A retrospective case review was conducted of 12 consecutive
      eyes with corneal decompensation secondary to Fuchs endothelial dystrophy that
      had been treated with DSAEK without concomitant removal of the crystalline lens
      from January 1, 2005 to July 1, 2007 at the University of Iowa Hospitals and
      Clinics. Eyes in which a minimum follow-up period of 12 months was available were
      included in the statistical analysis. RESULTS: Of the 10 eyes that met the
      inclusion criteria, visually significant cataracts occurred in 4 eyes (40%) in
      the first postoperative year and required surgical intervention. A significant
      difference in the mean anterior chamber depth was detected between eyes that
      developed cataracts and those that did not (P = 0.005). In 3 eyes, cataract
      development was associated with a preoperative anterior chamber depth of less
      than 2.80 mm. All 3 of these eyes developed pupillary block with markedly
      elevated intraocular pressure during the first 24 postoperative hours. After 24
      months, the 6 eyes that did not develop cataracts had a mean best spectacle
      corrected visual acuity of 20/24. Among the 4 eyes that required cataract
      surgery, the mean best spectacle-corrected visual acuity was 20/35. One eye had
      developed endothelial graft failure and required repeat DSAEK. CONCLUSIONS: The
      development of cataracts is common after phakic DSAEK and may be associated with
      considerable ocular morbidity.

PMID- 21099415
TI  - Tolerance and biocompatibility of micronized black pigment for keratopigmentation
      simulated pupil reconstruction.
AB  - PURPOSE: To study the tolerance and biocompatibility of new mineral micronized
      pigments for corneal cosmetic pigmentation in an experimental animal model.
      METHODS: Central corneal intralamellar tattoos were performed with a black iron
      oxide mineral micronized pigment using an irrigating solution as a control.
      Animals were examined regularly under a slit lamp to detect any signs of
      inflammation, pigment diffusion, or color changes and neovascularization. The
      animals were divided into 2 groups, A and B. These groups were followed up at 1
      and 3 months, respectively. At the end of this period, confocal microscopy
      examination was performed before the animals were killed, and their eyes were
      processed for histopathological examination to determine the level of pigment
      diffusion and inflammation and the presence of neovascularization. RESULTS:
      Clinical findings included 2 cases of minimal inflammation that resolved within 2
      weeks and a severe case of inflammation detected 20 days after the surgery.
      Confocal microscopy at the end of the follow-up revealed normal corneal
      structures in all the eyes examined, with a layer of highly reflective material
      in the mid stroma because of the presence of mineral pigment particles.
      Histopathological examination corroborated clinical results regarding
      inflammation. No pigment diffusion or changes in color occurred throughout the
      study, and there were no cases of corneal neovascularization. CONCLUSIONS:
      Central keratopigmentation presented good cosmetic appearance without adverse
      effects. These results suggest the adequacy of mineral micronized pigments for
      successful keratopigmentation. The hen animal model is a suitable model for
      assaying the biocompatibility and tolerance of micronized pigments in central
      keratopigmentation.

PMID- 21099416
TI  - Enteric-coated mycophenolate sodium as a corticosteroid-sparing agent for the
      treatment of autoimmune scleritis.
AB  - PURPOSE: To evaluate enteric-coated mycophenolate sodium (EC-MPS) as a
      corticosteroid-sparing agent in the treatment of autoimmune scleritis. METHODS: A
      retrospective, interventional, noncomparative review of EC-MPS use in patients
      with autoimmune scleritis. RESULTS: Seven eyes of 5 patients (all female; median
      age: 47 years, range: 20-55 years) with inflammatory scleral disease were treated
      with EC-MPS. The mean follow-up duration was 16.4 months (range, 12-20 months).
      EC-MPS was started at 360 mg twice daily. The mean time to treatment success was
      1.6 months (range, 1-3 months). The mean prednisolone dosage at the onset of EC
      MPS was 24 mg daily (range, 15-30 mg), and this was reduced to 6.5 mg daily
      (range, 0-10 mg) as inflammation control was achieved. No severe adverse events
      except for 1 patient with transient knee pain were reported; the incidence of
      adverse events after using EC-MPS was 1/6.83 person-years. There was no
      recurrence of scleral inflammation during the follow-up period. CONCLUSIONS: EC
      MPS can be used as a corticosteroid-sparing agent to safely suppress inflammatory
      autoimmune scleritis.

PMID- 21099417
TI  - A multicenter, double-blind, parallel group, placebo-controlled clinical study to
      examine the safety and efficacy of T-Clair SPHP700-3 in the management of mild to
      moderate dry eye in adults.
AB  - PURPOSE: To study the safety and efficacy of T-Clair SPHP700-3, a new over-the
      counter preservative-free formulation, in the management of mild to moderate dry
      eye in adults. METHODS: Sixty adult patients with mild to moderate dry eye were
      consecutively recruited in 2 eye clinics and randomized into 2 groups: treatment
      and placebo. Signs and symptoms of dry eye were compared along 28 days of
      treatment. RESULTS: No adverse events were reported during the study. Symptoms
      and signs of dry eye showed significant differences between the 2 groups after 2
      and 4 weeks of treatment. CONCLUSIONS: SPHP700-3 preservative-free formulation
      showed to be safe and effective in mild to moderate dry eye, improving tear film
      stability, ocular surface lubrification, and patients' symptomatology.

PMID- 21099419
TI  - Conjunctival-corneal intraepithelial neoplasia (Bowen disease) treated with
      orthovoltage.
AB  - PURPOSE: To report an exceptionally large conjunctival-corneal intraepithelial
      neoplasia (CCIN) (Bowen disease), for which the size of the tumor made classical
      treatment difficult, and to highlight the role of orthovoltage as an alternative
      treatment mode with good results. METHODS: Observational case report of a healthy
      61-year-old man with CCIN. Given its extension, alternative treatment was
      performed with orthovoltage, thus avoiding surgery, with adjuvant cryotherapy and
      mitomycin C, and potential complications. After administering topical anesthetic,
      a therapeutic contact lens was placed on the cornea; then, the eyelids were held
      open with a blepharostat. A 1-mm lead plate with a window was placed over the
      blepharostat. The shape of the window reproduced the shape of the tumor to
      protect the rest of the eye structures from radiation. Orthovoltage was
      administered with direct field radiation that was focused on the tumor through
      the window. The patient received 500 cGy in 2 sessions/week for 2 weeks (2000
      cGy) and then 7 sessions 300 cGy daily (2100 cGy). RESULTS: Evolution was good
      without side effects. After one-year follow-up, the patient was asymptomatic,
      without alterations of ocular surface or deep structures. CONCLUSIONS: Safely
      administered orthovoltage may be a good therapeutic option for the treatment of
      CCIN when complete surgical resection is complicated by the extension of the
      tumor. Compared with topical treatment, radiation is easier to administer,
      shortens and simplifies the treatment, and is independent of patient compliance.

PMID- 21099420
TI  - In vivo confocal microscopy and anterior segment optical coherence tomography in
      a case of alternaria keratitis.
AB  - PURPOSE: To report a case of Alternaria alternata keratitis analyzed with in vivo
      confocal microscopy (IVCM) and anterior segment optical coherence tomography
      (OCT). METHODS: A 68-year-old man with unilateral keratitis was evaluated using
      IVCM (Heidelberg Retina Tomograph II; Heidelberg, Germany) and anterior segment
      OCT (Visante OCT; Carl Zeiss Meditec, Dublin, CA). RESULTS: IVCM demonstrated the
      presence of small, round, hyperreflective cells surrounded by hyporeflective
      irregular areas and highly reflective dendritic shaped cells at the level of the
      epithelium. Stromal examination revealed many hypereflective filamentous
      structures, and some hyporeflective perpendicular lines and hyperreflective oval
      bodies were clearly visible along the filaments. Anterior segment OCT examination
      demonstrated a thickened cornea due to diffuse edema and an irregular corneal
      surface corresponding to the ulcer. There were hyperreflective areas beneath the
      epithelium representing the infiltrate. Microbiological examination of corneal
      scrapings demonstrated the presence of Alternaria alternata. After 1 month of
      antifungal treatment, IVCM demonstrated a significant reduction of the
      inflammatory cells and a hyperreflective scar-like tissue. Branching hyphal
      infiltrates were no longer present. OCT also documented the healing process and
      the complete recovery of the central and peripheral stromal thickness.
      CONCLUSIONS: IVCM and anterior segment OCT could be useful for the early
      diagnosis and treatment of fungal keratitis.

PMID- 21099423
TI  - Immunotactoid microtubular corneal deposits in bilateral paraprotein crystalline
      keratopathy and atypical corneal immunoglobulin deposition in a patient with
      dysproteinemia.

PMID- 21099424
TI  - Proof of principle: the predisposition, infection, response, organ failure sepsis
      staging system.
AB  - OBJECTIVE: In an effort to improve upon the traditional sepsis syndrome
      definitions, the predisposition, infection, response, organ dysfunction (PIRO)
      model was proposed to better characterize sepsis. The objective of this
      investigation was to derive and validate a sepsis staging system based on the
      PIRO concept that risk stratifies patients with suspected infection. DESIGN:
      Three independent, observational, prospective cohorts were studied. A derivation
      cohort (n = 2,132) was used to create the PIRO score, identifying independent
      predictors of mortality. Individual values were assigned to create the weighted
      integer score for each parameter, yielding the final PIRO score. The prognostic
      performance was then investigated in independent internal (n = 4,618) and
      external (n = 1,004) validation cohorts. SETTING: Two large U.S. tertiary care
      centers. PATIENTS: Patients admitted to the hospital from the emergency
      department with suspected infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The PIRO staging system was created by combining components of
      predisposition (age, chronic obstructive pulmonary disease, liver disease,
      nursing home residency, and malignancy with and without metastasis), infection
      (pneumonia and cellulitis), response (tachypnea, bandemia, and tachycardia), and
      organ dysfunction (renal, respiratory, cardiac, metabolic, and hematologic). The
      derived PIRO score showed stepwise increase in mortality with increasing points
      and high discriminatory ability with an area under the curve of 0.90 in the
      derivation cohort, 0.86 in internal validation, and 0.83 in external validation.
      CONCLUSIONS: This study provides evidence-based support for the PIRO approach to
      sepsis staging. Future efforts may utilize this approach with additional
      parameters (e.g., genetics and novel biochemical markers) to develop further the
      PIRO stratification system.

PMID- 21099425
TI  - Ionized calcium concentration and outcome in critical illness.
AB  - OBJECTIVE: To assess the association of abnormalities of ionized calcium levels
      with mortality in a heterogeneous cohort of critically ill patients. DESIGN:
      Retrospective, combined clinical and biochemical study. SETTING: Four combined
      medical/surgical intensive care units. PATIENTS: Cohort of 7,024 adult critically
      ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied
      177,578 ionized calcium measurements, from 7024 patients, with a mean value of
      1.11 mmol/L (ionized calcium measured every 4.5 hrs on average). The unadjusted
      lowest and highest ionized calcium reported during intensive care unit stay were
      significantly different between intensive care unit survivors and nonsurvivors (p
      < .001). If hypocalcemia occurred at least once during the intensive care unit
      stay, the probability of intensive care unit mortality increased by 46%, 108%,
      and 150% for ionized calcium levels <1.15, 0.90, and 0.80 mmol/L, respectively.
      If hypercalcemia occurred at least once during the intensive care unit stay, the
      probability of intensive care unit mortality increased by 100%, 162%, and 190%
      for ionized calcium levels >1.25, 1.35, and 1.45 mmol/L, respectively. Similar
      trends were seen for hospital mortality. However, from multivariate logistic
      regression analysis, only an ionized calcium <0.8 mmol/L or an ionized calcium
      >1.4 mmol/L were independently associated with intensive care unit and hospital
      mortality. CONCLUSIONS: Within a broad range of values, ionized calcium
      concentration has no independent association with hospital or intensive care unit
      mortality. Only extreme abnormalities of ionized calcium concentrations are
      independent predictors of mortality.

PMID- 21099427
TI  - Sonographic assessment of abdominal vein dimensional and hemodynamic changes
      induced in human volunteers by a model of abdominal hypertension.
AB  - OBJECTIVE: In patients affected by intra-abdominal hypertension, bladder or
      gastric pressure measurement may be usefully integrated by ultrasounds in order
      to detect early hemodynamic impairment. The purpose of this study was to search
      for changes in abdominal vein size and flow induced by intra-abdominal
      hypertension. DESIGN: Physiologic study. SETTING: Postoperative intensive care
      unit of a university hospital. SUBJECTS: Sixteen healthy volunteers.
      INTERVENTIONS: Four echographic assessments of vessel sizes and blood velocities
      were randomly performed in the following settings: 1) baseline, 2) intra
      abdominal hypertension simulated by a tight pelvic stabilizer around the waist,
      3) noninvasive ventilation with a facial mask, and 4) intra-abdominal
      hypertension plus noninvasive ventilation. MEASUREMENTS AND MAIN RESULTS: The
      model of intra-abdominal hypertension was validated in eight subjects by
      measuring gastric pressure. During intra-abdominal hypertension, 1) the inferior
      vena cava was compressed (significant decrease of both anteroposterior and
      lateral diameters) and deformed (decreased anteroposterior/lateral diameter
      ratio), and deformation, but not compression, was attenuated by noninvasive
      ventilation associated with intra-abdominal hypertension; 2) the portal vein was
      also compressed (decreased diameter); and 3) blood velocities did not change
      significantly in the inferior vena cava, portal vein, right suprahepatic vein, or
      right external iliac vein. In the receiver operating characteristic curve
      analysis, an inferior vena cava section area (normalized for body surface) of
      lower than 1 cm2/m2 discriminated between intra-abdominal hypertension presence
      and absence with a sensitivity of 65.6% and a specificity of 87.5% (p = .0001).
      Noninvasive ventilation alone did not significantly affect vein sizes and
      velocities. The resistive index, calculated by pulse wave Doppler signal from
      segmental branches of the right renal artery, increased slightly, but
      significantly, during intra-abdominal hypertension alone, suggesting an increase
      of intrarenal pressure. CONCLUSIONS: Simulated intra-abdominal hypertension was
      associated with decreased inferior vena cava section area and increased resistive
      index in renal arteries. Further studies are now needed to investigate whether
      these changes may be of value to integrate bladder or gastric pressure
      measurement in clinical practice.

PMID- 21099426
TI  - Elevation of blood urea nitrogen is predictive of long-term mortality in
      critically ill patients independent of "normal" creatinine.
AB  - OBJECTIVE: We hypothesized that elevated blood urea nitrogen can be associated
      with all-cause mortality independent of creatinine in a heterogeneous critically
      ill population. DESIGN: Multicenter observational study of patients treated in
      medical and surgical intensive care units. SETTING: Twenty intensive care units
      in two teaching hospitals in Boston, MA. PATIENTS: A total of 26,288 patients,
      age >= 18 yrs, hospitalized between 1997 and 2007 with creatinine of 0.80-1.30
      mg/dL. INTERVENTIONS: None. MEASUREMENTS: Blood urea nitrogen at intensive care
      unit admission was categorized as 10-20, 20-40, and >40 mg/dL. Logistic
      regression examined death at days 30, 90, and 365 after intensive care unit
      admission as well as in-hospital mortality. Adjusted odds ratios were estimated
      by multivariable logistic regression models. MAIN RESULTS: Blood urea nitrogen at
      intensive care unit admission was predictive for short- and long-term mortality
      independent of creatinine. Thirty days following intensive care unit admission,
      patients with blood urea nitrogen of >40 mg/dL had an odds ratio for mortality of
      5.12 (95% confidence interval, 4.30-6.09; p < .0001) relative to patients with
      blood urea nitrogen of 10-20 mg/dL. Blood urea nitrogen remained a significant
      predictor of mortality at 30 days after intensive care unit admission following
      multivariable adjustment for confounders; patients with blood urea nitrogen of
      >40 mg/dL had an odds ratio for mortality of 2.78 (95% confidence interval, 2.27
      3.39; p < .0001) relative to patients with blood urea nitrogen of 10-20 mg/dL.
      Thirty days following intensive care unit admission, patients with blood urea
      nitrogen of 20-40 mg/dL had an odds ratio of 2.15 (95% confidence interval, 1.98
      2.33; <.0001) and a multivariable odds ratio of 1.53 (95% confidence interval,
      1.40-1.68; p < .0001) relative to patients with blood urea nitrogen of 10-20
      mg/dL. Results were similar at 90 and 365 days following intensive care unit
      admission as well as for in-hospital mortality. A subanalysis of patients with
      blood cultures (n = 7,482) demonstrated that blood urea nitrogen at intensive
      care unit admission was associated with the risk of blood culture positivity.
      CONCLUSION: Among critically ill patients with creatinine of 0.8-1.3 mg/dL, an
      elevated blood urea nitrogen was associated with increased mortality, independent
      of serum creatinine.

PMID- 21099428
TI  - Large intestine.

PMID- 21099429
TI  - An update on irritable bowel syndrome: from diagnosis to emerging therapies.
AB  - PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a common functional
      gastrointestinal disorder characterized by abdominal discomfort or pain that is
      accompanied by a disturbance in defecation. Although the exact etiopathogenesis
      is not completely understood, recent advances in the understanding of the
      biochemical, physiologic, and biopsychosocial mechanisms of IBS have resulted in
      exciting new insights as well as therapies. This article will review the recent
      developments in pathogenesis, diagnosis, and treatment. RECENT FINDINGS: IBS may
      be the product of various pathogenic mechanisms which include IBS as a
      serotonergic disorder; the role of genetics; IBS as an inflammatory state and the
      potential role of mast cells; IBS as a result of bacterial overgrowth and altered
      gastrointestinal microbiome; and abnormal pain processing and pain memory.
      Emerging therapies have developed targeting these mechanisms. SUMMARY: IBS
      remains a symptom-based diagnosis that can usually be made comfortably based on
      clinical history without testing in the absence of alarm features. Novel and
      emerging therapies that are based upon the evolving understanding of the
      pathophysiology of IBS hold significant promise and for the first time there are
      potential therapies that may alter the natural history of this disorder.

PMID- 21099430
TI  - New molecular approaches in the diagnosis of acute diarrhea: advantages for
      clinicians and researchers.
AB  - PURPOSE OF REVIEW: To provide an update of the advantages of new-generation
      molecular diagnostics as regards acute diarrhea, and to evaluate how they can
      help clinicians and researchers diagnose this condition. RECENT FINDINGS: Thanks
      to real-time polymerase chain reaction techniques, many enteropathogens can now
      be identified simultaneously within hours. Most techniques are based on
      amplification of specific nucleotide sequences. With high-resolution melting
      analyses, microarrays, and metagenomic analyses, multiple genomic sequences can
      be evaluated in a single sample; thus, a wide range of enteropathogens can be
      evaluated in one run. Molecular techniques have elucidated the role of major
      enteropathogens such as norovirus and bocavirus and their evolving epidemiology.
      They have revealed novel transmission routes, also in food-borne diarrhea
      outbreaks, and have opened the way to new therapies and preventive measures, as
      well as to surveillance of emerging rotavirus strains after vaccine introduction.
      SUMMARY: Molecular approaches are best suited for epidemiologic purposes and for
      selected clinical conditions such as early identification of treatable agents in
      at-risk patients, rather than for cases requiring only oral rehydration. In the
      field of acute diarrhea, the major application of molecular techniques is the
      identification of novel agents of gastroenteritis and their epidemiology.

PMID- 21099431
TI  - Inflammatory bowel disease and colitis: new concepts from the bench and the
      clinic.
AB  - PURPOSE OF REVIEW: The previous 18 months have shown important progress in
      unravelling the causes of inflammatory bowel disease (IBD) and in improving its
      management for the patients. RECENT FINDINGS: More genome-wide association
      studies and meta-analyses of these have been published and have identified more
      than 100 confirmed genes for IBD, and highlighted a number of novel pathways. Two
      of the genes, NOD2/CARD15 and the autophagy gene ATG16L1 have recently been
      linked into one functional pathway of bacterial sensing, invasion and
      elimination. From the clinical side, the previous year has been dominated mainly
      by the results of the SONIC study, comparing efficacy and safety of azathioprine,
      infliximab and the combination of azathioprine and infliximab, in patients with
      active Crohn's disease, naive to these drugs. International consensus guidelines
      on infection prevention were released last year by the European Crohn's and
      Colitis Organisation. SUMMARY: The recent findings in IBD include the increasing
      number of IBD susceptibility genes, the demonstration that NOD2 and ATG16L1 are
      linked in one functional pathway and the role of IL-33/ST2 in colitis. From the
      bedside, the novelties have been the results of SONIC and selecting the right
      patient for intensified treatment with immunomodulators and anti-tumor necrosis
      factor, and appropriate counselling regarding risk of infections and
      vaccinations.

PMID- 21099432
TI  - Update on Clostridium difficile infection.
AB  - PURPOSE OF REVIEW: This review summarizes the most recent epidemiological data
      and advances in research into the pathogenesis, diagnosis and treatment of
      Clostridium difficile infection (CDI). RECENT FINDINGS: The epidemiology of CDI
      has changed with the emergence of hypervirulent strains. CDI rates have increased
      in the community, in children and in patients with inflammatory bowel disease.
      Although the North American pulsed-field gel electrophoresis type 1, restriction
      endonuclease analysis group BI, PCR ribotype 027 (NAP1/BI/027) strain remains
      prevalent in North America, surveillance suggests that it is decreasing in
      Europe. A similar strain, PCR ribotype 078, is emerging which is associated with
      community-associated CDI and has been isolated in animals and food products. The
      Society for Healthcare Epidemiology of America and the Infectious Diseases
      Society of America have published new guidelines on the epidemiology, diagnosis,
      treatment, infection control and environmental management of C. difficile.
      Several novel therapies for CDI are at different stages of development. There
      have been promising trial results with fidaxomicin, a novel antibiotic for the
      treatment of CDI and monoclonal antibodies against toxins A and B, which have
      been shown to significantly reduce CDI recurrence rates. SUMMARY: Major advances
      have been made in our understanding of the spread and pathogenesis of C.
      difficile and new treatment options are becoming available.

PMID- 21099433
TI  - Practice patterns of cardiologists, general practitioners, and internists for
      managing supraventricular tachycardias in Greece.
AB  - OBJECTIVES: Supraventricular tachycardias (SVT) often lead to emergency room and
      primary care visits. Not only cardiologists, but also general practitioners (GPs)
      and internists are involved to an increasing extent in the acute and long-term
      management of SVT. We aimed to explore the differences between practice patterns
      of cardiologists and noncardiologists with regard to SVT management in Greece.
      METHODS: A cross-sectional questionnaire survey was conducted among 250
      cardiologists and 250 GPs/internists from various areas across Greece. RESULTS: A
      response rate of 61.8% was obtained. Vagal maneuvers were the initial therapeutic
      approach for SVT termination; however, 22% of noncardiologists would rather start
      with an antiarrhythmic drug. Adenosine was the most popular drug for SVT
      termination, but the GPs/internists would use it less often than the
      cardiologists (67 vs. 86%, P<0.001). The GPs/internists would keep the patient
      for at least 24 h or more after SVT termination, while 48% of the cardiologists
      would discharge the patient within the first 3 h. Noncardiologists would more
      often suggest a 24-h Holter recording than the cardiologists (73 vs. 55%,
      P<0.005). With regard to the long-term management of SVT, the GPs/internists
      would prescribe antiarrhythmic drugs earlier than the cardiologists, and seem to
      be less familiar with the indications for the electrophysiological testing and
      ablation. CONCLUSION: Significant differences in practice patterns exist in
      Greece with regard to SVT management between cardiologists and noncardiologists.
      The GPs/internists seem to rely more on antiarrhythmic drugs and tend to
      underestimate the role of ablation therapy for the long-term management of SVT.

PMID- 21099434
TI  - Hepatic encephalopathy: from pathophysiology to therapeutic management.
AB  - Hepatic encephalopathy is a complex and potentially reversible neuropsychiatric
      syndrome complicating acute or chronic liver disease. Clinical manifestations are
      multiple and varied, ranging from minimal neurological changes to coma. Ammonia
      is the main toxic substance involved in the pathogenesis of hepatic
      encephalopathy, although other mechanisms, such as modifications of the blood
      brain barrier, disruptions in neurotransmission and abnormalities in GABAergic
      and benzodiazepine pathways may also play a role. The identification and
      treatment of precipitating factors is crucial in the management of patients with
      hepatic encephalopathy. Current treatments are based on reducing intestinal
      ammonia load by agents such as antibiotics or disaccharides, although their
      efficacy is yet to be clearly established.

PMID- 21099435
TI  - Pharmacokinetics of colistin in an adolescent boy with extensive burn injury.
AB  - Multidrug resistance in Gram-negative bacteria has led to a resurgence in
      colistin use. No pharmacokinetic data exist for burn patients. A 17-year-old boy
      suffered a 71% TBSA full-thickness burn with deep necrosis and compartment
      syndrome. He developed multidrug-resistant Acinetobacter baumannii burn wound
      sepsis/septic shock with acute renal failure requiring dialysis. The organism was
      resistant to all tested antibiotics except colistin. He received colistin 2.5
      mg/kg every 24 hours. Peak and trough serum concentrations, area under the
      concentration-time curve, and elimination half-lives of colistin were 3.6 +/- 1.0
      MUg/ml, 0.9 +/- 0.5 MUg/ml, 47.1 +/- 14.4 mg . hr/L, and 12.3 +/- 9.4 hours (mean
      +/- SD), respectively. Serum levels were at or above the minimum inhibitory
      concentration for >90% of therapy. Nevertheless, salvage therapy with colistin
      proved futile as the patient developed acidosis, coagulopathy, and was
      vasopressor-dependent without any wound healing. He died on hospital day 52.
      Microbiologically, the serum levels of colistin were seemingly adequate, as
      repeat cultures were negative. Given the peak and trough levels of colistin
      relative to the minimum inhibitory concentration for the organism (0.5 MUg/ml),
      it would seem that the dosage of 2.5 mg/kg administered every 24 hours for this
      patient on dialysis was appropriate. Patients on dialysis infected with an
      organism possessing a higher inhibitory concentration (>=1 MUg/ml) should
      probably receive the same dosage every 12 hours to avoid subtherapeutic
      concentrations. Large-scale study of the pharmacokinetics of colistin in patients
      with burn injury is urgently needed.

PMID- 21099436
TI  - Distraction histogenesis in ankle burn deformities.
AB  - Burn injuries involving the joints around the lower extremity often lead to
      debilitating postburn contractures that frequently compromise extremity
      functions. Treatment of such injuries, especially involving the ankle and foot
      area, is very challenging. Conservative management has limited efficiency in
      correcting the deformities, whereas open surgical treatment is often coupled with
      high complication rates because of poor soft-tissue coverage and poor vascularity
      around the burnt areas. The use of the Ilizarov fixator has the advantage of
      tackling these deformities without the need for extensive open surgical
      procedures, which will minimize complications and recurrences. The authors
      present a series of three patients, two adults and one pediatric patient, who
      were treated successfully with minimally invasive surgery and soft-tissue
      distraction with the Ilizarov apparatus.

PMID- 21099437
TI  - Patterns of medical and developmental comorbidities among children presenting
      with feeding problems: a latent class analysis.
AB  - OBJECTIVE: Children with feeding problems often have multiple co-occurring
      medical and developmental conditions; however, it is unknown whether patterns of
      comorbidity exist and whether they relate to important feeding-related health
      outcomes. The main objective of this study was to examine (1) the relationship
      between the number of medical and developmental comorbidities and important
      feeding-related health outcomes; (2) how various comorbidities interact and form
      empirically derived patterns; and (3) how empirically derived patterns of
      comorbidity relate to weight status, nutritional variety, and child and parent
      mealtime behavior problems. METHODS: The medical records of 286 children (mean
      age = 35.56 months) seen at an outpatient feeding disorders clinic were reviewed.
      Child weight status, nutritional variety, and child and parent mealtime behavior
      problems were assessed using standardized measures. The lifetime occurrence of
      medical and developmental conditions was reliably coded. Empirically derived
      patterns of comorbidity were generated via latent class analyses. RESULTS: Latent
      class analyses generated 3 comorbidity patterns: "Behavioral" (58% of cases),
      "Developmentally Delayed" (37%), and "Autism Spectrum Disorder" (ASD, 5%). The
      Autism Spectrum Disorder group was found to have less nutritional variety
      compared to the Behavioral and Developmentally Delayed groups. No differences
      were found between groups in terms of percent ideal body weight, or severity of
      child or parent mealtime behavior problems. CONCLUSION: Multiple co-occurring
      conditions of children with feeding problems were empirically reduced to 3
      patterns of comorbidities. Comorbidity patterns were largely unrelated to weight
      status and child or parent mealtime behavior problems. This suggests that medical
      and developmental conditions confer general, rather than specific, risk for
      feeding problems in children.

PMID- 21099438
TI  - Humeral lengthening and deformity correction with the multiaxial correction
      system.
AB  - Limb lengthening for humeral length discrepancy is typically accomplished using a
      traditional monolateral external fixator frame or an Ilizarov-type device, which
      have distinct shortcomings for the correction of concomitant deformity and
      application to the upper extremity, respectively. A new monolateral frame, the
      multiaxial correction (MAC) system, provides advantage over other monolateral
      frames and Ilizarov-type devices for humeral lengthening and may achieve similar
      outcomes. The purpose of this study was to report on the use of the MAC system
      for limb lengthening in pediatric patients, each with humeral length discrepancy
      and deformity. Surgical technique for applying the frame to the humerus is
      described briefly. A retrospective review of all pediatric patients with humeral
      length discrepancy treated with the MAC system by one orthopedic surgeon at a
      major teaching hospital was performed. Clinical data, operative records, and
      radiographs were reviewed for each patient. A total of three humeri in three
      children were lengthened over a 3-year period. There were two girls and a boy,
      with a mean age of 10.3 +/- 1.9 years. Etiologies for their discrepancies were
      osteomyelitis and posttraumatic physeal arrest. Mean initial humeral length
      discrepancy was 9.4 +/- 2.3 cm. All patients had proximal varus deformities,
      which were partially corrected during treatment. Mean lengthening was 6.5 +/- 0.8
      cm, and mean healing index was 27.1 +/- 4.1 days/cm. Mean follow-up was 23.0 +/-
      9.9 months. There were no major complications. In conclusion, the MAC system is
      well suited to the correction of humeral length discrepancies and associated
      humeral deformities in children. LEVEL OF EVIDENCE: level IV case series.

PMID- 21099439
TI  - Incidentally found situs inversus totalis with congenitally corrected
      transposition of the great arteries in a 75-year-old woman.
AB  - We describe a 75-year-old woman with previously undiagnosed situs inversus
      totalis with congenitally corrected transposition of the great arteries, who was
      admitted to the hospital due to exertional dyspnea and orthopnea. Diagnosis was
      made by electrocardiogram-gated 64-slice multidetector-row computed tomography.

PMID- 21099440
TI  - Patient use of smartphones to communicate subjective data in clinical trials.
AB  - PURPOSE: Various methods have been used in clinical trials to collect time
      sensitive subjective responses, including study diaries, telephone interviews,
      and use of text messaging. However, all of these methods are limited by the
      uncertainty of when the participants enrolled in the study actually record their
      responses. This technical note reports on the utility of the BlackBerry
      smartphone to collect such data and why such a system provides advantages over
      other methods to report subjective ratings in clinical studies. METHODS: The
      Centre for Contact Lens Research developed an on-line web-enabled system that
      permits participants to record and immediately transmit subjective rating scores
      in numerical form directly into a web-enabled database. This, combined with the
      utility of BlackBerrys, enabled time-specific e-mail requests to be sent to the
      study participants and then for that data to be simultaneously transmitted to the
      web-enabled database. This system has been used in several clinical trials
      conducted at the Centre for Contact Lens Research, in which data were collected
      at various times and in several specific locations or environments. RESULTS: In
      the clinical trials conducted using this system, participants provided responses
      on 97.5% of occasions to the requests for data generated by the automated system.
      When the request was for data on a set date, this method resulted in responses of
      84.1% of the time. CONCLUSIONS: The series of clinical trials reported here show
      the benefits of the utilization of the BlackBerry to collect time- or environment
      sensitive data via a web-enabled system.

PMID- 21099441
TI  - Ocular problems in HIV and AIDS patients in Nigeria.
AB  - PURPOSE: To investigate ocular disease and visual acuity defects in patients with
      HIV/AIDS according to CD4T-cells counts. METHODS: The CD4T lymphocyte counts of
      all the volunteers were obtained. Visual acuity, refraction, ophthalmoscope, and
      slitlamp examinations were performed on each patient after the CD4T-cell count
      result was obtained. RESULTS: Young adults aged between 21 and 30 years were
      mostly affected, 39 (97.5%) of the HIV patients had refractive errors, and 10
      (25%) had reduced vision. Seven (17.5%) moderate and one (2.5%) severe low vision
      patients were found between 499 to 0 and 299 to 200 CD4T-cell counts,
      respectively. Ocular diseases found in various CD4T-cells counts were proptosis
      (2.5%), orbital cellulitis (2.5%), and cytomegalovirus retinitis (2.5%) in 99 to
      0, keratoconjunctivitis sicca (2.5%) and corneal keratitis (2.5%) in 499 to 400,
      molluscum contagiosum (2.5%) in 299 to 200, iridocyclitis (2.5%) in 199 to 100,
      cloudy media (22.5%), red eyes (30%), poor pupillary reflexes (17.5%), and
      painful eye (30%) in 499 to 0, retinal exudates (15%), disc edema (30%), and
      choroidoretinitis (15%) in 399 to 0, ocular toxoplasmosis (5%) and herpes zoster
      (7.5%) in 299 to 100, Kaposi sarcoma (12.5%) in 199 to 0, conjunctivitis (7.5%)
      in 499 to 300, and uveitis (7.5%) in 399 to 200. There were significant
      differences between visual acuity of the control and the HIV/AIDS patients, p <
      0.05. CONCLUSIONS: Ocular impairments increased with decrease in CD4T-cells
      counts. Additional studies are required in predicting the CD4T-cells counts that
      will serve as a marker for specific ocular disease manifestation in HIV/AIDS.

PMID- 21099442
TI  - Imaging and Perimetry Society standards and guidelines.
AB  - PURPOSE: To provide readers with standards, recommendations, guidelines, and
      requirements for the application of perimetry to clinical ophthalmic practice and
      scientific study. METHODS: A working group of perimetry and visual field
      specialists from many parts of the world constructed a document that would allow
      current and future perimeters to be assessed by the same criteria. Because
      hardware and software technology, statistical procedures and clinical conditions
      are constantly changing, the characteristics in this paper emphasize general
      concepts rather than specific implementations employed by current devices.
      RESULTS: Critical aspects of perimetry included indications for perimetry,
      perimetric techniques, stimulus characteristics, test administration, patient
      preparation, data display, statistical analysis, interpretation of visual field
      findings, a glossary of terms and definitions, and standards for comparison of
      different perimetric tests. Each of these topics is discussed, along with their
      advantages and disadvantages. CONCLUSIONS: These guidelines serve as a basis for
      practitioners to evaluate their perimetric needs in relation to their clinical
      practice and patient population so that informed decisions can be made for visual
      field testing. In addition, these issues should be used as a cornerstone for
      future technological and practical improvements to the visual field diagnostic
      procedures.

PMID- 21099443
TI  - Trichinellosis in children and adults: a 10-year comparative study in Western
      Romania.
AB  - INTRODUCTION: This study aims to evaluate and compare the epidemiologic,
      laboratory, clinical, and therapeutic aspects of trichinellosis in child and
      adult populations residing in Western Romania. PATIENTS AND METHODS: We have
      retrospectively investigated the medical records of patients with trichinellosis
      hospitalized between 1996 and 2005 in 5 infectious diseases hospitals located in
      4 Western Romanian counties. RESULTS: Trichinellosis was diagnosed in 1344
      patients, of whom 348 were children (26%) and 996 were adults (74%). The annual
      average incidence was 8.4 cases per 100,000 in children and 7.7 cases per 100,000
      in adults. The mean ages for the children and adults were 11 +/- 4.4 years and
      38.1 +/- 14.2 years, respectively. Myalgias and complications of trichinellosis
      were detected less frequently in children who also had lower eosinophil counts,
      leukocyte counts, and erythrocyte sedimentation rates compared with those for
      adults. Albendazole and mebendazole had comparable efficacies in adult patients;
      however, albendazole proved to be a better choice than mebendazole for the
      treatment of children. CONCLUSIONS: Trichinellosis occurs commonly among
      inhabitants of Western Romania. Although the general trend of decline in the
      incidence of trichinellosis cases cannot be used as a statistical predictor of
      future improvement, it provides encouragement and demonstrates the need for the
      implementation of correct public health and educational measures to fully prevent
      and eradicate trichinellosis in Western Romania.

PMID- 21099444
TI  - Effectiveness of haemophilus influenzae type B conjugate vaccine for prevention
      of meningitis in Senegal.
AB  - A total of 24 cases of hospitalized, laboratory-confirmed Haemophilus influenzae
      type b (Hib) meningitis were identified through a regional pediatric bacterial
      meningitis surveillance system. Each case was matched by age and residence to 4
      neighborhood controls. The adjusted vaccine effectiveness for >= 2 doses was
      95.8% (95% confidence interval, 67.9%-99.4%). Hib vaccine appears to be highly
      effective in preventing Hib meningitis in Senegal.

PMID- 21099445
TI  - Frequency of ureaplasma serovars in respiratory secretions of preterm infants at
      risk for bronchopulmonary dysplasia.
AB  - OBJECTIVE: Ureaplasma respiratory tract colonization is associated with
      bronchopulmonary dysplasia (BPD) in preterm infants. Whether the 4 Ureaplasma
      parvum and 10 Ureaplasma urealyticum serovars differ in virulence is unknown.
      This study was conducted to determine the distribution of Ureaplasma serovars in
      respiratory secretions of a prospective cohort of preterm infants and to assess
      whether any of the serovars are associated with BPD. METHODS: Serial endotracheal
      and/or nasopharyngeal aspirates were obtained for Ureaplasma culture and PCR from
      136 infants of gestational age <33 weeks. All positive samples were speciated and
      serovars were determined by real-time PCR. RESULTS: A total of 51 (37.5%) infants
      were Ureaplasma-positive one or more times during the first month of life.
      Respiratory colonization was inversely related to gestational age. Sixty-five
      percent of infants <26 weeks compared with 31% infants >= 26 weeks were culture
      or PCR positive. U. parvum was more common (N = 32, 63%) than U. urealyticum (N =
      17, 33%); both species were present in 2 samples. Serovars 3 and 6 alone and in
      combination accounted for 96% U. parvum isolates. U. urealyticum isolates were
      commonly a mixture of multiple serovars, with serovar 11 alone or combined with
      other serovars (10/17, 59%) being the most common serovar. No individual species
      or serovars or serovar mixtures were associated with moderate-to-severe BPD.
      CONCLUSIONS: U. parvum serovars 3 and 6 and U. urealyticum serovar 11 were the
      most common serovars detected in respiratory samples from a prospective cohort of
      preterm infants.

PMID- 21099446
TI  - Secular trends in antibiotic use among neonates: 2001-2008.
AB  - BACKGROUND: Few data exist on time trends of antibiotic consumption among
      neonates. OBJECTIVES: To assess secular trends in antibiotic consumption in the
      context of an antibiotic policy and the effect of antibiotic use on the
      development of antimicrobial resistance and outcome among neonates in a single
      center. METHODS: We performed a prospective cohort study between 2001 and 2008 to
      monitor antibiotic consumption among neonates. In parallel, we initiated a policy
      to shorten antibiotic therapy for clinical sepsis and for infections caused by
      coagulase-negative staphylococci and to discontinue preemptive treatment when
      blood cultures were negative. Time trend analyses for antibiotic use and
      mortality were performed. RESULTS: In total, 1096 of 4075 neonates (26.7%)
      received 1281 courses of antibiotic treatment. Overall, days of therapy were 360
      per 1000 patient-days. Days of therapy per 1000 patient-days decreased yearly by
      2.8% (P < 0.001). Antibiotic-days to treat infections decreased yearly by 6.5% (P
      = 0.01) while antibiotic-days for preemptive treatment increased by 3.4% per year
      (P = 0.03). Mean treatment duration for confirmed infections decreased by 2.9%
      per year (P < 0.001). No significant upward trend was observed for infection
      associated mortality. Of 271 detected healthcare-associated infections, 156
      (57.6%) were microbiologically documented. The most frequent pathogens were
      coagulase-negative staphylococci (48.5%) followed by Escherichia coli (13.5%) and
      enterococci (9.4%). Rates for extended-spectrum beta-lactamase-producing
      microorganisms and methicillin-resistant Staphylococcus aureus remained low.
      CONCLUSIONS: Shortening antibiotic therapy and reducing preemptive treatment
      resulted in a moderate reduction of antibiotic use in the neonatal intensive care
      unit and did not increase mortality.

PMID- 21099447
TI  - Th1 and Th2 chemokines, vaccine-induced immunity, and allergic disease in infants
      after maternal omega-3 fatty acid supplementation during pregnancy and lactation.
AB  - We investigated whether the previously reported preventive effect of maternal
      omega-3 fatty acid supplementation on IgE-associated allergic disease in infancy
      may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile
      in the infant. Vaccine-induced immune responses at 2 y of age were also
      evaluated. Pregnant women, at risk of having an allergic infant, were randomized
      to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g
      docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of
      breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24
      mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC
      chemokine ligand 17 (CCL17) levels were associated with infant allergic disease
      (p < 0.05). In infants without, but not with, maternal history of allergy, the
      omega-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11
      (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in
      allergic infants, omega-3 supplementation was linked with higher Th1-associated
      CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p =
      0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant
      immune system toward a less Th2-dominated response, by maternal omega-3 fatty
      acid supplementation, seems to be influenced by allergic status.

PMID- 21099448
TI  - Modulation of sodium transport in alveolar epithelial cells by estradiol and
      progesterone.
AB  - The effects of estradiol (E2) and progesterone (P) on alveolar epithelial Na+
      transport were studied in isolated alveolar epithelial cells from 18- to 19-d GA
      rat fetuses, grown to confluence in serum-free media supplemented with E2 (0-1
      MUM) and P (0-2.8 MUM). Short-circuit currents (ISC) were measured, showing an
      increase by E2 and P in a dose-dependent manner. The Na,K-ATPase subunits -alpha1
      and -beta1 were detected by Western blotting, but total expression was not
      significantly altered. Furthermore, all three epithelial Na+ channel (ENaC)
      subunits -alpha, -beta, and -gamma were detected, with trends toward a higher
      expression in the presence of E2 and P. Real-time PCR revealed an increase of
      alpha- and beta-ENaC expression but no alteration of gamma-ENaC. In addition, the
      mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) and
      Na,K-ATPase-beta1 subunit were elevated in the presence of E2 and P. Single
      channel patch clamp analysis demonstrated putative highly selective and
      nonselective cation channels in the analyzed cells, with a higher percentage of
      responsive patches under the influence of E2 and P. We conclude that E2 and P
      increased Na+ transport in alveolar epithelial cells by enhancing the expression
      and activity of ENaC and Na,K-ATPase.

PMID- 21099449
TI  - A murine model for disseminated candidiasis in neonates.
AB  - Candida albicans is the leading fungal pathogen causing invasive disease in
      immunocompromised patients including the neonate. A reliable animal model for
      disseminated candidiasis in the neonate is needed to study the unique aspects of
      this host-pathogen interaction. To establish such a model, 2-d-old BALB/c mouse
      pups were given i.p. injections with varied inocula of C. albicans or saline
      control. Pups were examined every 3-8 h for death. Surviving pups were killed at
      72 h. Kidney, lung, spleen, liver, and brain were homogenized and plated for
      colony counts and/or fixed for histological staining. The i.p. injection of C.
      albicans led to mortality in a dose-dependent fashion. Disseminated infection was
      confirmed by colony counts of homogenized kidney, lung, and brain, as well as by
      histological examination. Infection with a C. albicans mutant lacking the cell
      surface adhesin, Als3p, led to significant reduction in mortality relative to WT
      (p = 0.03). This model will be useful to study the unique aspects of antifungal
      defense in a neonatal host and will provide a means to test novel therapeutic
      strategies.

PMID- 21099450
TI  - Postpartum depression symptoms: a case-control study on monoaminergic functional
      polymorphisms and environmental stressors.
AB  - OBJECTIVE: Postpartum depression (PPD) is an under diagnosed and under treated
      mood disorder, with negative impact on both the mother and the infant's health.
      The aim of this study is to examine whether genetic variations in the
      monoaminergic neurotransmitter system, together with environmental stressors,
      contribute to the development of PPD symptoms. METHODS: This nested case-control
      study included 275 women from a population-based cohort of delivering women in
      Sweden. A questionnaire containing the Edinburgh Postnatal Depression Scale was
      collected at 6 weeks and 6 months postpartum. Three functional polymorphisms were
      genotyped, catechol-O-methyltransferase (COMT)-Val158Met, monoamine oxidase A
      (MAOA)-upstream variable number tandem repeat (uVNTR) and serotonin transporter
      linked polymorphic region (5HTT-LPR). Stressful life events, maternity stressors
      and previous psychiatric contact were considered as potential risk factors.
      RESULTS: COMT-Val158Met was significantly associated with PPD symptoms at 6
      weeks, but not at 6 months postpartum. A significant gene-gene interaction effect
      was present between COMT-Val158Met and MAOA-uVNTR. In a gene-environment
      multivariate model, COMT-Val158Met, psychiatric contact and maternity stressors
      were significantly associated with PPD symptoms. Among those with history of
      psychiatric problems, the COMT-Val158Met and 5HTT-LPR risk variants were
      associated with PPD symptoms, whereas in the absence of previous psychiatric
      contact only maternity stressors were related to PPD symptoms. CONCLUSION: The
      interaction effect between monoaminergic genes and environmental stressors is
      likely to contribute to vulnerability for PPD. The different patterns of
      association according to history of psychiatric problems, if replicated, might be
      helpful in screening strategies.

PMID- 21099452
TI  - intravitreal tumor necrosis factor inhibitors in the treatment of refractory
      diabetic macular edema: a pilot study from the Pan-American Collaborative Retina
      Study Group.
AB  - PURPOSE: The purpose of this study was to report the short-term visual and
      anatomical outcomes after intravitreal injections of two different tumor necrosis
      factor alpha inhibitors in eyes with refractory diabetic macular edema. METHODS:
      An interventional, retrospective, multicenter study of 39 eyes with refractory
      diabetic macular edema that were injected with adalimumab (n = 5 for 2 mg) or
      infliximab (n = 15 for 1 mg; n = 19 for 2 mg). The main outcome measures were the
      best-corrected visual acuity and the central macular thickness at 3 months of
      follow-up. RESULTS: In the 1-mg infliximab group, the logarithm of the minimal
      angle of resolution best-corrected visual acuity improved from 1.49 +/- 0.58 at
      baseline to 1.38 +/- 0.56 at 3 months (P = 0.6991). In the 2-mg infliximab group,
      the logarithm of the minimal angle of resolution best-corrected visual acuity
      worsened from 0.76 +/- 0.54 to 1.03 +/- 0.69 at 3 months (P = 0.5995). In the
      adalimumab group, the logarithm of the minimal angle of resolution best-corrected
      visual acuity improved from 1.44 +/- 0.77 to 1.08 +/- 0.85 at 3 months (P =
      0.2500). The central macular thickness in the 1-mg infliximab group decreased
      from 459 +/- 125 MUm at baseline to 388 +/- 131 MUm at 3 months (P = 0.1178). In
      the 2-mg infliximab group, the central macular thickness remained unchanged from
      378 +/- 97 MUm at baseline to 349 +/- 118 MUm at 3 months (P = 0.2162). In the
      adalimumab group, the central macular thickness remained unchanged from 521 +/-
      163 MUm at baseline to 526 +/- 390 MUm at 3 months (P = 0.1250). There were no
      systemic side effects reported in any of the patients. However, laboratory
      markers for autoimmunity were not done. None of the eyes injected with either
      adalimumab or 1 mg of infliximab had adverse ocular events. In the 2-mg
      infliximab group, 42% (8 of 19) of eyes developed severe uveitis. Three of these
      eyes (37.5%) required pars plana vitrectomy. The uveitis in the remaining five
      eyes resolved with topical steroid therapy. CONCLUSION: Both intravitreal
      adalimumab and infliximab do not appear to benefit eyes with refractory diabetic
      macular edema. Intravitreal injections of infliximab may elicit a severe
      intraocular inflammatory reaction.

PMID- 21099454
TI  - Ischemic index and neovascularization in central retinal vein occlusion.
AB  - PURPOSE: To explore the association of angiographic nonperfusion with anterior
      segment and posterior segment neovascularization in central retinal vein
      occlusion (CRVO). METHODS: An imaging database at one institution was searched
      for the diagnosis of central retinal vein occlusion. Ultra wide field fluorescein
      angiograms were graded for image quality, the presence of retinal
      neovascularization, and the quantity of nonperfusion; an ischemic index (ISI) was
      calculated. Charts were reviewed to exclude eyes with previous treatment and to
      determine which eyes had anterior segment or posterior segment neovascularization
      on the day of the angiogram. Time from onset to presentation could not accurately
      be ascertained. RESULTS: In a 39-month period, there were 69 eyes that met
      inclusion criteria. The mean ISI was 25% (SD, 26%; range, 0-100%), and 15 eyes
      (21%) with neovascularization had a mean ISI of 75% (range, 47-100%) compared
      with eyes without neovascularization that had an ISI of 6% (range, 0-43%).
      Ischemic index significantly correlated to neovascularization, and eyes that had
      evidence of neovascularization had an ISI >45% (P < 0.0001). CONCLUSION: Ultra
      wide field fluorescein angiography provides visualization of nonperfusion in eyes
      with central retinal vein occlusion. Eyes with neovascularization on the day of
      the angiogram were found to have significantly larger areas of retinal
      nonperfusion compared with eyes without neovascularization. A prospective study
      is indicated to know if early treatment of peripheral retinal nonperfusion in
      CRVO improves outcomes.

PMID- 21099536
TI  - Notes from the net nomad....

PMID- 21099453
TI  - Posterior vitreous detachment with microplasmin alters the retinal penetration of
      intravitreal bevacizumab (Avastin) in rabbit eyes.
AB  - PURPOSE: Intravitreal bevacizumab (BV) (Avastin, Genentech Inc., South San
      Francisco, CA) is frequently used for the treatment of age-related macular
      degeneration. Previous studies have demonstrated full-thickness retinal
      penetration. Intravitreal recombinant microplasmin (MP) has been shown to
      successfully induce a posterior vitreous detachment (PVD) and vitreous
      liquefaction in animals. It has been suggested that a PVD may alter the retinal
      penetration of molecules in the vitreous cavity. The aim of this study was to
      compare BV retinal penetration in rabbit eyes with and without an MP-induced PVD.
      METHODS: Twelve adult rabbits were injected with 0.1 mL (0.4 mg) of MP into the
      vitreous cavity of 1 eye. One week later, the rabbits were injected with 0.05 mL
      (1.25 mg) of BV into both eyes. Both eyes of 3 rabbits were harvested at 6 hours,
      12 hours, 24 hours, and 72 hours after the BV injection. Frozen retinal cross
      sections were prepared, and BV retinal penetration was evaluated with
      immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes
      from one rabbit were not injected with either agent and used as controls to
      compare the background autofluorescence. Peripapillary retinal sections were
      recorded with a digital camera, and intraretinal BV fluorescence-labeled antibody
      was measured by qualitative photographic interpretation. Two additional rabbits
      received an intravitreal injection of 0.1 mL of MP in 1 eye. One week later, both
      eyes from each rabbit were enucleated, and frozen retinal sections were prepared
      and analyzed with light microscopy to evaluate histologic damage. RESULTS: Full
      thickness BV retinal penetration was observed throughout the retina in both eyes
      of each rabbit. All the MP-injected eyes exhibited increased antibody labeling in
      retinas evaluated at 6 hours, 12 hours, and 24 hours after BV injection when
      compared with the contralateral non-MP-injected eyes. By 3 days after BV
      injection, all eyes demonstrated decreased antibody labeling compared with
      earlier periods. At 3 days, 1 rabbit showed increased antibody labeling in the
      retina of the non-MP-injected eye compared with the contralateral MP-injected
      eye, and 2 rabbits exhibited similar antibody labeling in both eyes. When
      compared with control eyes, light microscopy demonstrated normal retinal
      histologic findings in eyes injected only with MP. CONCLUSION: Increased BV
      retinal penetration is observed initially in eyes with an MP-induced PVD, and the
      mechanism is likely multifactorial. By 3 days, retinal penetration is similar in
      eyes with and without a PVD. Although it is difficult to directly extrapolate to
      humans, our study suggests that a PVD may alter the retinal penetration of BV.

PMID- 21099537
TI  - Data aggregation: a case study.

PMID- 21099538
TI  - Database management systems--their place in nursing informatics education.

PMID- 21099539
TI  - Creating an Excel chart with a double axis to compare two data types.

PMID- 21099540
TI  - Designing a tailored Web-based educational mammography program.
AB  - Breast cancer has become increasingly prevalent in Taiwanese women, especially in
      younger women. Unfortunately, early breast cancer detection may be hampered by
      Taiwanese women's beliefs about breast cancer, risk factors, and mammography. The
      Internet has become a powerful way to disseminate health information, but health
      education Web sites are frequently neither patient-centered nor theoretically
      based. We used the Transtheoretical Model as the theoretical basis for the design
      of a tailored Web-based educational program aimed at correcting Taiwanese women's
      misconceptions about breast cancer and mammography and increasing their intent to
      obtain routine mammography. In this article, we describe the Web-based
      educational intervention and the results of an initial preliminary evaluation
      study.

PMID- 21099541
TI  - Computer-mediated support for adolescents with cerebral palsy or spina bifida.
AB  - Social support plays a key role in improving health outcomes for children with
      chronic conditions. Internet connections are an important component of
      adolescents' social networks and may overcome geographic and environmental
      barriers for those with disabilities. This article focuses on the processes
      associated with a 6-month online support intervention for adolescents with
      cerebral palsy or spina bifida. Specifically, the purpose was to determine the
      extent to which adolescents used an online peer support intervention, the
      processes used, and the perceived benefits and satisfaction with the
      intervention. Five peer mentors with the same disabilities provided information,
      affirmation, and emotional support. The online environment created a safe space
      to foster reciprocal interpersonal connections and appropriate social comparison.
      Two-thirds of the participants viewed the computer-mediated support intervention
      as fun. Factors influencing the perceived utility of the intervention included
      typing speed, cognitive skills, and perceived need for additional support. Girls
      were significantly more likely to contribute messages than were boys. Peer
      mentors wished that this type of support program had been available when they
      were teens, appreciated the supportive elements, and reported learning from the
      teen participants. Health professionals wanting to implement online support need
      to consider the age and ability levels of participants and the optimal length and
      format of the support program.

PMID- 21099543
TI  - Evaluating clinical decision support rules as an intervention in clinician
      workflows with technology.
AB  - The implementation of electronic health records in rural settings generated new
      challenges beyond those seen in urban hospitals. The preparation, implementation,
      and sustaining of clinical decision support rules require extensive attention to
      standards, content design, support resources, expert knowledge, and more. A
      formative evaluation was used to present progress and evolution of clinical
      decision support rule implementation and use within clinician workflows for
      application in an electronic health record. The rural hospital was able to use
      clinical decision support rules from five urban hospitals within its system to
      promote safety, prevent errors, establish evidence-based practices, and support
      communication. This article describes tools to validate initial 54 clinical
      decision support rules used in a rural referral hospital and 17 used in clinics.
      Since 2005, the study hospital has added specific system clinical decision
      support rules for catheter-acquired urinary tract infection, deep venous
      thrombosis, heart failure, and more. The findings validate the use of clinical
      decision support rules across sites and ability to use existing indicators to
      measure outcomes. Rural hospitals can rapidly overcome the barriers to prepare
      and implement as well as sustain use of clinical decision support rules with a
      systemized approach and support structures. A model for design and validation of
      clinical decision support rules into workflow processes is presented. The
      replication and reuse of clinical decision support rule templates with data
      specifications that follow data models can support reapplication of the rule
      intervention in subsequent rural and critical access hospitals through system
      support resources.

PMID- 21099545
TI  - The Omaha system and meaningful use: applications for practice, education, and
      research.
AB  - Meaningful use has become ubiquitous in the vocabulary of health information
      technology. It suggests that better healthcare does not result from the adoption
      of technology and electronic health records, but by increasing interoperability
      and informing clinical decisions at the point of care. Although the initial
      application of meaningful use was limited to eligible professionals and
      hospitals, it incorporates complex processes and workflow that involve all
      nurses, other healthcare practitioners, and settings. The healthcare community
      will become more integrated, and interdisciplinary practitioners will provide
      enhanced patient-centered care if electronic health records adopt the priorities
      of meaningful use. Standardized terminologies are a necessary component of such
      electronic health records. The Omaha System is an exemplar of a standardized
      terminology that enables meaningful use of clinical data to support and improve
      patient-centered clinical practice, education, and research. It is user-friendly,
      generates data that can be shared with patients and their families, and enables
      healthcare providers to analyze and exchange patient-centered coded data. Use of
      the Omaha System is increasing steadily in diverse practice, education, and
      research settings nationally and internationally.

PMID- 21099544
TI  - A nursing virtual intervention: real-time support for managing antiretroviral
      therapy.
AB  - Based on a philosophy of empowerment, we developed the HIV Treatment, Virtual
      Nursing Assistance and Education intervention to equip persons living with HIV
      for managing their daily antiretroviral therapies. In this article, we describe
      the project and the process of developing it, which was carried out in three
      phases: (1) development of the intervention's clinical content, (2) generation of
      a multimedia presentation, and (3) implementation of our Web application via
      computer interface. The HIV Treatment, Virtual Nursing Assistance and Education
      consists of four interactive sessions at the computer, animated by a virtual
      nurse that takes the individual through the learning process about the
      capabilities necessary for taking the treatment. This information and strategies
      provided by the virtual nurse are specifically adapted to the participant,
      according to the responses he/she supplies. The virtual intervention approach,
      still experimental, is intended to be complementary with the actual clinical
      follow-up and has been developed in the context of reorganizing services and of
      the scarcity of resources. While we anticipate direct positive outcomes among the
      HIV clientele, it is also highly probable that this virtual support application
      will have ramifications among different clienteles who must also contend with the
      daily challenges of their health conditions.

PMID- 21099546
TI  - Information systems use, benefits, and satisfaction among Ohio RNs.
AB  - Contemporary forces, including the growing nursing shortage, the aging
      population, and the emphasis on patient safety, are increasing the pressure on
      healthcare facilities to use information systems to achieve better outcomes. Use
      of information systems improves nurses' ability to make decisions in a timely
      manner; however, nurses are still reluctant about or avoiding using information
      systems in their daily work. The purpose of this study was to explore the
      relationships among age, nursing education, computer experience, user involvement
      in implementation, nursing management support to use information systems, nurses'
      information system use, and information system outcomes (benefits and
      satisfaction). The study used an input-process-outcome framework, a descriptive
      correlational design, and a mailed survey with a random sample of staff nurses.
      Computer experience, user involvement, and nursing management support were found
      to significantly explain information system use. In addition, information system
      use was found to significantly explain nurses' perception of the benefits of
      using information systems and their satisfaction with using information systems.
      These results assist nursing administrators and leaders to change and/or
      restructure the appropriate work environment to enhance nurses' information
      system use and increase their satisfaction, thereby improving patient outcomes.

PMID- 21099547
TI  - Nursing profession reengineered for leadership in landmark report: special report
      for the alliance for nursing informatics member organizations.

PMID- 21099551
TI  - Exploring relationships between hospital patient safety culture and adverse
      events.
AB  - OBJECTIVES: There has been very limited research linking staff perceptions of
      hospital patient safety culture with rates of adverse clinical events. This
      exploratory study examined relationships between the Agency for Healthcare
      Research and Quality's (AHRQ) Hospital Survey of Patient Safety Culture and rates
      of in-hospital complications and adverse events as measured by the AHRQ Patient
      Safety Indicators (PSIs). The general hypothesis was that hospitals with a more
      positive patient safety culture would have lower PSI rates. METHODS: We performed
      multiple regressions to examine the relationships between 15 patient safety
      culture variables and a composite measure of adverse clinical events based on 8
      risk-adjusted PSIs from 179 hospitals, controlling for hospital bed size and
      ownership. All patient safety culture data were collected in 2005 and 2006
      (except 1 late 2004 hospital), and all PSI data were collected in 2005. RESULTS:
      Nearly all of the relationships tested were in the expected direction (negative),
      and 7 (47%) of the 15 relationships were statistically significant. All
      significant relationships were of moderate size, with standardized regression
      coefficients ranging from -0.15 to -0.41, indicating that hospitals with a more
      positive patient safety culture scores had lower rates of in-hospital
      complications or adverse events as measured by PSIs. CONCLUSIONS: Our findings
      support the idea that a more positive patient safety culture is associated with
      fewer adverse events in hospitals. Further research is needed to determine the
      generalizability of these results to larger sets of hospitals and to examine the
      causal relationship between patient safety culture and clinical patient outcomes.

PMID- 21099552
TI  - Trigger thumb of the dominant hand in identical twins.

PMID- 21099554
TI  - Visualization of the anterior cerebral artery complex with a continuously
      variable-view rigid endoscope: new options in aneurysm surgery.
AB  - BACKGROUND: Neuroendoscopy is increasingly used as an adjunctive tool in
      intracranial aneurysm surgery. OBJECTIVE: To assess the versatility of a
      prototype continuously variable-view rigid endoscope in visualizing the anterior
      cerebral artery complex. METHODS: In 5 formaldehyde-fixed, arterially injected
      specimens, a standard frontolateral approach was used on both sides. After
      meticulous microsurgical dissection using this approach, the prototype of a
      multivariable rigid endoscope (EndoCAMeleon; Karl Storz GmbH & Co, Tuttlingen,
      Germany) was inserted. It is a rigid endoscope that is capable of changing its
      angle of view while remaining stationary and shape invariant. We inspected the
      anterior cerebral artery complex, using and testing the capabilities of the
      device. RESULTS: The continuously variable viewing mechanism enables the surgeon
      to adjust the field of view continuously and to optimize the visualization of the
      neurovascular structures. Because of the rigid tip combined with the continuously
      variable viewing mechanism, the need to move the endoscope within the surgical
      field was minimal. The field of view changes, but the tip itself hardly moves.
      The EndoCAMeleon was able to enhance both the visibility of the anterior cerebral
      artery complex and the accessibility of the A1 and A2 arterial walls to a range
      of approximately 270 degrees. CONCLUSION: The EndoCAMeleon enhances the
      visibility of the anterior cerebral artery complex and facilitates endoscope
      assisted inspection, planning of clip application, and clip control.

PMID- 21099555
TI  - Recording of surgical processes: a study comparing senior and junior
      neurosurgeons during lumbar disc herniation surgery.
AB  - BACKGROUND: Evaluating surgical practice in the operating room is difficult, and
      its assessment is largely subjective. OBJECTIVE: Recording of standardized spine
      surgery processes was conducted to ascertain whether any significant differences
      in surgical practice could be observed between senior and junior neurosurgeons.
      METHODS: Twenty-four procedures of lumbar discectomies were consecutively
      recorded by a senior neurosurgeon. In 12 cases, surgery was entirely performed by
      a senior neurosurgeon with the aid of a resident, and in the 12 remaining cases,
      surgery was performed by a resident with the aid of a senior neurosurgeon. The
      data recorded were general parameters (operating time for the whole procedure and
      for each step), and general and specific parameters of the surgeon's activities
      (number of manual gestures, number and duration of actions performed, use of the
      instruments, and use of interventions on anatomic structures). The Mann-Whitney U
      test was used for comparison between the 2 groups of neurosurgeons. RESULTS: The
      operating time was statistically lower for the group of senior surgeons. The
      seniors statistically demonstrated greater economy in time and in gestures during
      the closure step, for sewing and for the use of scissors, needle holders, and
      forceps. The senior surgeons statistically worked for a shorter time on the skin
      and used fewer manual gestures on the thoracolumbalis fascia. The number of
      changes in microscope position was also statistically lower for this group.
      CONCLUSION: There is a relationship between surgical practice, as determined by a
      method of objective measurement using observation software, and surgical
      experience: gesture economy evolves with seniority.

PMID- 21099556
TI  - A novel aneurysm clip design for atheromatous, thrombotic, or previously coiled
      lesions: preliminary experience with the "compression clip" in 6 cases.
AB  - BACKGROUND: Large and giant lesions often have thicker, atheromatous walls as
      well as intra-aneurysmal thrombus that combine to prevent traditional clips from
      closing properly in some cases. OBJECTIVE: To report the development and use of a
      novel clip design specifically tailored to treat atheromatous, thrombotic, or
      previously coiled aneurysms. METHODS: We retrospectively reviewed the records of
      6 patients with complex aneurysms not amenable to simple neck clipping and not
      considered appropriate for endovascular therapy who were treated using a novel
      "compression" clip design. We describe the development and use of a novel
      aneurysm clip design with blades that are not opposed at rest to allow direct
      clipping of atheromatous, thrombotic, and previously coiled aneurysms. RESULTS:
      Four patients had recurrent, previously coiled aneurysms; one of these also had a
      large thrombotic component. Two patients had complex lesions with heavy atheroma
      involving a portion of their aneurysms. There were no complications related to
      the use of the clip, and all patients did well without neurological
      complications. In every case, the clip allowed straightforward obliteration of
      the aneurysm without the need for temporary vascular occlusion, aneurysmorrhaphy,
      or removal of an intra-aneurysmal coil mass. All patients underwent
      intraoperative angiography to confirm obliteration of the aneurysm with
      preservation of the normal vasculature. CONCLUSION: Atheromatous, thrombotic, and
      previously coiled aneurysms may not be treatable with simple neck clipping and
      may not be curable with endovascular therapy. For such cases, we designed a novel
      "compression" clip that has been used safely and successfully in our experience
      with good short-term follow-up.

PMID- 21099557
TI  - Water jet dissection in neurosurgery: an update after 208 procedures with special
      reference to surgical technique and complications.
AB  - BACKGROUND: Water jet dissection represents a promising technique for precise
      brain tissue dissection with preservation of blood vessels. In the past, the
      water jet dissector has been used for various pathologies. A detailed report of
      the surgical technique is lacking. OBJECTIVE: The authors present their results
      after 208 procedures with a special focus on surgical technique, intraoperative
      suitability, advantages, and disadvantages. METHODS: Between March 1997 and April
      2009, 208 patients with various intracranial neurosurgical pathologies were
      operated on with the water jet dissector. Handling of the device and its
      usefulness and extent of application were assessed. The pressures encountered,
      potential risks, and complications were documented. The patients were followed 1
      to 24 months postoperatively. RESULTS: A detailed presentation of the surgical
      technique is given. Differences and limitations of the water jet dissection
      device in the various pathologies were evaluated. The water jet dissector was
      intensively used in 127 procedures (61.1%), intermittently used in 56 procedures
      (26.9%), and scarcely used in 25 procedures (12%). The device was considered to
      be very helpful in 166 procedures (79.8%) and helpful to some extent in 33
      procedures (15.9%). In 8 (3.8%) procedures, it was not helpful, and in 1
      procedure (0.5%), the usefulness was not documented by the surgeon. CONCLUSION:
      The water jet dissector can be applied easily and very safely. Precise tissue
      dissection with preservation of blood vessels and no greater risk of
      complications are possible. However, the clinical consequences of the described
      qualities need to be demonstrated in a randomized clinical trial.

PMID- 21099558
TI  - Interfascial technique for vertebral artery exposure in the suboccipital
      triangle: the road map.
AB  - BACKGROUND: The extradural portion of the vertebral artery (VA-V3) has a unique
      anatomy at the craniovertebral junction. The exposure of V3 can be accompanied by
      profuse bleeding from the venous plexus in addition to the potential risk of
      inadvertent injury of the VA during surgery at the craniovertebral junction. The
      natural tissue planes represent a road map to the safe exposure of the VA in the
      suboccipital triangle. OBJECTIVE: To describe the microsurgical anatomy of the
      tissue planes in the suboccipital region. METHODS: The suboccipital region was
      bilaterally dissected in 6 fresh silicone-injected cadaver heads. An interfascial
      technique was used to expose the VA-V3 following a tissue plane between the deep
      suboccipital muscular fascia dorsally and posterior atlantooccipital membrane,
      the C1 periosteal membrane, and the membrane covering the VA and venous plexus
      ventrally. The craniovertebral junction was harvested from 2 heads and prepared
      for histological sections. The same technique was applied in 25 operative cases.
      RESULTS: The anatomic dissections confirmed the existence of an interfascial
      plane that can be dissected in a blunt fashion to reach as far lateral as the
      transverse processes of C1 and C2. Application of the dissection technique did
      not require diathermy coagulation in the operating room. In 25 cases, there was
      no injury of the VA or bleeding from the venous plexus. CONCLUSION: Vertebral
      artery exposure in the suboccipital triangle (V3) can be achieved safely with
      minimal blood loss using a technique that follows the natural tissue plane
      between the deep suboccipital muscle fascia, the posterior atlantooccipital
      membrane, the membrane covering VA/venous plexus, and the periosteum of the C1
      and C2 laminae.

PMID- 21099559
TI  - Latex injection of cadaver heads: technical note.
AB  - BACKGROUND: Latex injection of cadaveric heads is an alternative to the standard
      technique of silicone injection. Thorough injections of the arterial and venous
      systems can be achieved by analyzing the anatomic and physiological variations of
      the vascular system of each specimen during the initial irrigation phase to
      tailor the subsequent latex injection. OBJECTIVE: To report on an improved method
      for color latex injection of cadaveric specimens using these techniques. METHODS:
      Thirty-two cadaver heads were injected and preserved for anatomic dissection. The
      critical steps included (1) cannulation of the cervical arteries and veins with
      Foley or Coude catheters, (2) "indirect" anatomic study of the vasculature during
      irrigation with water of the major arteries and veins, (3) fixation of the
      specimen with either formaldehyde or alcohol, and (4) color injection of the
      arteries and veins with red and blue latex, respectively. The injected specimens
      were dissected and assessed qualitatively for the extent and detail of arterial
      and venous filling. Assessment and recording of flow characteristics from the
      specimens during water irrigation of the arterial and venous systems dictated the
      order and technique for subsequent latex injections. RESULTS: Latex injections
      resulted in deeper penetration of colored solutions into small cerebral vessels
      and mesenchymal structures. Of 32 injected specimens, 25 (78%) had outstanding
      injections and 7 (21.8%) had suboptimal results. Latex solutions are simpler to
      use than silicone solutions. CONCLUSION: Latex injection of cadaveric heads based
      on indirect anatomic and physiological assessment of the vasculature of the
      specimen during the water irrigation phase results in outstanding specimens for
      microanatomical studies.

PMID- 21099560
TI  - Waterjet dissection of peripheral nerves: an experimental study of the sciatic
      nerve of rats.
AB  - BACKGROUND: Although waterjet dissection has been well evaluated in intracranial
      pathologies, little is known of its qualities in peripheral nerve surgery.
      Theoretically, the precise dissection qualities could support the separation of
      nerves from adjacent tissues and improve the preservation of nerve integrity in
      peripheral nerve surgery. OBJECTIVE: To evaluate the potential of the new
      waterjet dissector in peripheral nerve surgery. METHODS: Waterjet dissection with
      pressures of 20 to 80 bar was applied on the sciatic nerves of 101 rats. The
      effect of waterjet dissection on the sciatic nerve was evaluated by clinical
      tests, neurophysiological examinations, and histopathological studies up to 12
      weeks after surgery. RESULTS: With waterjet pressures up to 30 bar, the sciatic
      nerve was preserved in its integrity in all cases. Functional damaging was
      observed at pressures of 40 bar and higher. However, all but 1 rat in the 80 bar
      subgroup showed complete functional regeneration at 12 weeks after surgery.
      Histopathologically, small water bubbles were observed around the nerves. At 40
      bar and higher, the sciatic nerves showed signs of direct nerve injury. However,
      all these animals showed nerve regeneration after 12 weeks, as demonstrated by
      histological studies. CONCLUSION: Sciatic nerves were preserved functionally and
      morphologically at pressures up to 30 bar. Between 40 and 80 bar, reliable
      functional and morphological nerve regeneration occurred. Waterjet pressures up
      to 30 bar might be applied safely under clinical conditions. This technique might
      be well suited to separate intact peripheral nerves from adjacent tumor or scar
      tissue. Further studies will have to show the clinical relevance of these
      dissection qualities.

PMID- 21099561
TI  - Lateral transzygomatic approach to sphenoid wing meningiomas.
AB  - BACKGROUND: Sphenoid wing meningiomas are slow-growing, well-circumscribed, and
      histologically benign lesions. The recurrence rate is low if removed completely
      at the time of surgery. Adequate surgical exposure with minimal morbidity is a
      challenge for those treating these lateral skull base lesions. OBJECTIVE: To
      describe our experience with the lateral tranzygomatic approach for resection of
      sphenoid wing meningioms in which the entire zygoma is mobilized and remains
      vascularized by masseter muscle attachments. METHODS: A retrospective review of
      the records of 19 patients who underwent sphenoid wing meningioma resection via a
      lateral transzygomatic approach between 1997 and 2007 was performed. A
      confirmatory cadaver dissection was performed to illustrate the anatomic nature
      of the technique. To achieve maximal exposure and minimal brain retraction, a
      lateral transzygomatic approach with osteotomies of the entire zygoma, which
      remains pedicled on the masseter muscle, was used. RESULTS: Nineteen patients
      with sphenoid wing meningioma underwent resection via a lateral transzygomatic
      approach. Complete resection of the meningioma was achieved in 17 cases.
      Morbidity consisted of temporary frontal nerve weakness (57.9%), mild to moderate
      temporalis atrophy (36.8%), and diplopia (15.8%). There were no cases of wound
      infection, bone malunion, or resorption. A mean follow-up period of 33.1 months
      (range, 2-71 months) revealed no recurrences after surgery as demonstrated by
      computed tomography or magnetic resonance imaging. CONCLUSION: The lateral
      transzygomatic approach to the sphenoid wing can be performed safely with minimal
      morbidity and facilitates complete resection of the tumor. Complete removal at an
      early stage is the best prognostic factor in treating sphenoid wing meningioma.
      This approach belongs in the armamentarium of surgeons who are involved in the
      resection of skull base neoplasms.

PMID- 21099562
TI  - The basal temporal approach for mesial temporal surgery: sparing the Meyer loop
      with navigated diffusion tensor tractography.
AB  - BACKGROUND: Visual field defects are a common side effect after mesial temporal
      resections such as selective amygdalohippocampectomy (SelAH). OBJECTIVE: To
      present a method of diffusion tensor tractography (DTT) of the Meyer loop for
      preoperative planning of the surgical approach for SelAH and for intraoperative
      visualization on a navigation-guided operating microscope. METHODS: Twelve
      patients were selected for SelAH to treat mesial temporal lobe epilepsy. All
      received preoperative MRI with diffusion tensor imaging sequences. The Meyer loop
      was determined and reconstructed as an object with DTT. Images were utilized for
      preoperative planning in which a safe approach not affecting the Meyer loop was
      specified. A navigation-guided operating microscope was used for image-guided
      surgery. RESULTS: DTT was a reliable method for visualization of the Meyer loop.
      Reconstruction of the Meyer loop had a direct impact on the approach planning. In
      all 12 cases, the optic tract could only be spared using a basal approach. Ten
      patients underwent SelAH by the subtemporal approach, and 2 underwent SelAH by
      the transcortical approach through the inferior temporal gyrus. During the
      critical early phase of the operation image guidance remained accurate until
      entry into the ventricle. Nine of 12 patients had no postoperative field deficits
      (75%). Three patients (25%) experienced peripheral incomplete quadrantanopia.
      CONCLUSION: DTT and intraoperative visualization of the Meyer loop is a helpful
      tool for preoperative planning and during surgery to find a safe trajectory to
      mesial temporal structures while avoiding the optic radiation. This technique in
      combination with a basal approach seems to be a promising strategy to prevent
      postoperative visual field deficits in most patients.

PMID- 21099563
TI  - Midline filum of the sellar dura: a useful landmark during endoscopic
      transsphenoidal pituitary surgery.
AB  - BACKGROUND: During endoscopic transsphenoidal pituitary surgery, identification
      and constant awareness of the midline is imperative to prevent injury to critical
      lateral structures, such as the internal carotid arteries. OBJECTIVE: To describe
      the relevance of a midline filum of the sellar dura which, when present, can
      serve as a useful intraoperative anatomic marker. METHODS: Intraoperative video
      recordings of twenty patients undergoing endoscopic transsphenoidal surgery were
      retrospectively reviewed to assess for the presence and location of a midline
      dural filum or apparent central dural vascular structure. Prospective
      intraoperative data were gathered on an additional 16 patients. RESULTS: A
      midline dural filum was identified in 18 of 36 patients (50%) undergoing
      endoscopic transsphenoidal surgery. This structure was identified on the midline
      in all cases, as confirmed by intraoperative neuronavigation and comparison with
      the vomer. The midline dural filum was identified as a strand-like dural
      extension (13 patients) or as a small vascular dural structure usually exhibiting
      low pressure venous bleeding (5 patients). Samples of the midline dural filum
      were obtained from 2 patients for histopathological analysis, which demonstrated
      dense collagenous connective tissue without evidence of vessel wall or ductal
      epithelium. CONCLUSION: In addition to anatomic structures such as the vomer and
      midline sphenoid sinus septations, a midline dural filum serves as a useful
      marker during the sellar phase of endoscopic transsphenoidal surgery. Along with
      intraoperative neuronavigation and Doppler ultrasonography of the cavernous
      carotid arteries, identification of this structure may further aid in
      safeguarding against injury to critical paramedian structures.

PMID- 21099564
TI  - Septal vein symmetry: implications for endoscopic septum pellucidotomy.
AB  - BACKGROUND: Endosopic septum pellucidotomy is used for treating patients with
      unilateral and specific types of bilateral hydrocephalus. The ideal location for
      septostomy is controversial; however, an avascular region is preferred.
      OBJECTIVE: As the septal veins (SVs) are viewed only from one side, we studied
      the symmetry of the SVs in an attempt to define a safe area for septostomy.
      METHODS: Sixteen cadaver brains were dissected. The septum pellucidum was exposed
      bilaterally and divided into 3 regions. SVs of both sides were evaluated
      according to number, size, distribution, and location relative to common markers
      on both sides. RESULTS: Each side included 1 to 7 large veins (mean +/- standard
      deviation, 2.3 +/- 1.4), 0 to 3 small veins (2.05 +/- 1.73), and a total of 2 to
      7 veins (4.35 +/- 1.53). Of the large veins, 88% were located in the anterior
      septal region (anterior to the foramen of Monro). Among the 10 brains that were
      extensively dissected, 90% had asymmetric SVs (either in the number of large
      veins or in the existence of any veins) in at least 1 of the septal regions, and
      50% of brains had asymmetric SVs in the anterior region. CONCLUSION: Distribution
      of the SVs is asymmetric in most cases. We recommend septostomy be performed at
      the anterior area of the middle septal region, at the level of the foramen of
      Monro, mid-height between the corpus callosum and fornix. Careful evaluation of
      preoperative images and thorough coagulation at the septostomy site are essential
      to avoid injury to a contralateral large SV.

PMID- 21099565
TI  - Fascicular topography of the suprascapular nerve in the C5 root and upper trunk
      of the brachial plexus: a microanatomic study from a nerve surgeon's perspective.
AB  - BACKGROUND: In patients with supraclavicular injuries of the brachial plexus, the
      suprascapular nerve (SSN) is frequently reconstructed with a sural nerve graft
      coapted to C5. As the C5 cross-sectional diameter exceeds the graft diameter,
      inadequate positioning of the graft is possible. OBJECTIVE: To identify a
      specific area within the C5 proximal stump that contains the SSN axons and to
      determine how this area could be localized by the nerve surgeon, we conducted a
      microanatomic study of the intraplexal topography of the SSN. METHODS: The right
      sided C5 and C6 roots, the upper trunk with its divisions, and the SSN of 20
      adult nonfixed cadavers were removed and fixed. The position and area occupied by
      the SSN fibers inside C5 were assessed and registered under magnification.
      RESULTS: The SSN was monofascicular in all specimens and derived its fibers
      mainly from C5. Small contributions from C6 were found in 12 specimens (60%). The
      mean transverse area of C5 occupied by SSN fibers was 28.23%. In 16 specimens
      (80%), the SSN fibers were localized in the ventral (mainly the rostroventral)
      quadrants of C5, a cross-sectional area between 9 o'clock and 3 o'clock from the
      surgeon's intraoperative perspective. CONCLUSION: In reconstruction of the SSN
      with a sural nerve graft, coaptation should be performed in the rostroventral
      quadrant of C5 cross-sectional area (between 9 and 12 o'clock from the nerve
      surgeon's point of view in a right-sided brachial plexus exploration). This will
      minimize axonal misrouting and may improve outcome.

PMID- 21099566
TI  - Fusiform aneurysms of the anterior communicating artery: illustrative series of 5
      cases with operative techniques.
AB  - BACKGROUND: Fusiform anterior communicating artery (ACoA) aneurysms (ACoAAs) are
      rare, and a series of these aneurysms has not been reported. Large fusiform ACoAA
      are easily identifiable, whereas smaller ones can coexist with a saccular
      component. OBJECTIVE: To provide a clear-cut definition, report the incidence of
      these aneurysms, present a series with follow-up data, and discuss operative
      nuances and clip application techniques. METHODS: Review of a single-surgeon
      operative series of all ACoAAs to identify fusiform types. When A1 or A2 vessels
      entered or arose from the ACoAA, it was classified as fusiform. Follow-up imaging
      and clinical progress were noted. RESULTS: Five fusiform ACoAAs were identified.
      Patient age ranged from 19 to 68 years. Anatomy varied from very obvious large
      fusiform, to identifiable fusiform nature with a saccular component, to an
      irregularly shaped aneurysm with a fusiform element of the ACoA. A large fusiform
      aneurysm reconstructed in 1 patient recurred 11 years later as a ruptured
      fusiform ACoAA that was reconstructed again. One patient had a giant thrombosed
      aneurysm with thrombosed vessels in which A2 reconstruction was attempted with
      sacrifice of the ACoA. In others, simple clipping achieved obliteration of the
      aneurysm together with creating a normal dimension ACoA. There were no operative
      deaths; other than rupture intraoperatively, no other complications occurred.
      Postoperatively, no patient had new neurological deficits, 3 had short-term
      memory loss, and all were ambulatory with good speech function. CONCLUSION:
      Review of angiograms and 3-dimensional computed tomography angiography
      reconstruction images can identify the complex and fusiform entity of ACoAA,
      which is important for preoperative planning. Experience in operative techniques
      and thorough knowledge of the ACoA anatomy are cornerstones to obliterate the
      aneurysm, maintain flow in all vessels, and surgically create an ACoA of normal
      caliber.

PMID- 21099567
TI  - Management of the great mimicker: Meckel cave tumors.
AB  - BACKGROUND: Meckel cave tumors are often asymptomatic and have a sufficiently
      characteristic magnetic resonance imaging/computed tomography signature that
      allows treatment/surveillance decisions to be made without biopsy confirmation.
      Radiographic diagnosis requires the surgeon to be fully aware of the plethora of
      unusual Meckel cave lesions that mimic benign tumors when they are malignant,
      inflammatory, or infectious and in need of a completely different and often
      timely intervention. When such a diagnosis is considered, it behooves the surgeon
      and benefits the patient to have a percutaneous biopsy technique available.
      OBJECTIVE: To use our recent experience with a patient with idiopathic
      inflammatory sensory neuropathy and another with Meckel cave lymphoma to review
      the management of tumors of the Meckel cave. METHODS: The technique of
      percutaneous biopsy of Meckel cave tumors through the foramen ovale with biopsy
      needles is detailed. CONCLUSION: Obtaining tissue biopsy percutaneously prevents
      patients with Meckel cave tumors best treated with nonsurgical management from
      undergoing open surgical resection with its concomitant morbidity.

PMID- 21099568
TI  - Stabilization of the atlantoaxial joint with C1-C3 lateral mass screw constructs:
      biomechanical comparison with standard technique.
AB  - BACKGROUND: Anatomically and biomechanically, the atlantoaxial joint is unique
      compared with the remainder of the cervical spine. OBJECTIVE: To assess the in
      vitro stability provided by 2 C2 screw sparing techniques in a destabilized model
      of the atlantoaxial joint and compare with the gold standard system. METHODS: The
      3-dimensional intervertebral motion of 7 human cadaveric cervical spine specimens
      was recorded stereophotogrammetrically while applying nonconstraining,
      nondestructive pure moments during flexion-extension, left and right axial
      rotation, and left and right lateral bending. Each specimen was tested in the
      intact state, followed by destabilization (odontoidectomy) and fixation as
      follows: (1) C1 and C3 lateral mass screws rods with sublaminar wiring of C2 (LC1
      C3 + SW), (2) C1 and C3 lateral mass screws rods with a cross-link in the C1-2
      interlaminar space (LC1-C3 + CL), (3) C1 and C3 lateral mass screw rods alone
      (negative control), and (4) C1 lateral mass and C2 pedicle screws rods augmented
      with C1-2 interspinous wire and graft (LC1-PC2, control group). RESULTS: Compared
      with the intact spine, each instrumented state significantly stabilized range of
      motion and lax zone at C1-2 (P < .001, 1-way repeated-measures analysis of
      variance). LC1-C3 + SW was equivalent to LC1-PC2 during flexion and lateral
      bending and superior to LC1-C3 + CL during lateral bending, while LC1-C3 + CL was
      equivalent to LC1-PC2 only during flexion. In all other comparisons, LC1-PC2 was
      superior to both techniques. CONCLUSION: From a biomechanical perspective, both
      C2 screw sparing techniques provided sufficient stability to be regarded as an
      alternative for C1-2 fixation. However, because normal motion across C2-3 is
      sacrificed, these constructs should be used in patients with unfavorable anatomy
      for standard fixations.

PMID- 21099569
TI  - Hemispherectomy for the control of intractable epilepsy in childhood: comparison
      of 2 surgical techniques in a single institution.
AB  - BACKGROUND: Hemispherectomy is an established neurosurgical procedure for
      catastrophic epilepsy in childhood. However, the technique used to achieve an
      optimum outcome remains to be determined. OBJECTIVE: We examined the influence of
      hemidecortication (HD) vs peri-insular hemispherotomy (PIH) on patient outcome.
      METHODS: The medical records of 41 children undergoing hemispherectomy were
      reviewed for patient demographics, clinical criteria, and surgical outcomes.
      RESULTS: HD and PIH were performed in 21 and 20 children, respectively. The mean
      age at surgery for HD was 54 months and 61 months for PIH. The median durations
      of surgery for HD and PIH were 5 hours and 7 hours, respectively (P < .001). For
      HD, 6 patients required a second surgery and 3 required a third. One PIH patient
      required a second procedure. Postoperative shunting was required in 5 HD
      patients, but only 1 PIH patient. All patients had increased hemiparesis after
      surgery. The overall mean follow-up time was 72 months. Engel class I or II
      outcomes after initial surgery were better after PIH (85%) compared with HD (48%)
      (P < .02). After subsequent surgeries for seizure control, 4 HD patients and 1
      PIH patient improved to Engel class I or II. CONCLUSION: Hemispherectomy is an
      effective surgical procedure for childhood intractable catastrophic epilepsy. In
      patients with diffuse hemispheric disorder, PIH tends to have fewer major
      complications, more favorable seizure outcomes, and a decreased need for
      subsequent surgical procedures, including shunting for hydrocephalus, compared
      with HD.

PMID- 21099570
TI  - Improving targeting in image-guided frame-based deep brain stimulation.
AB  - BACKGROUND: Deep brain stimulation (DBS) is commonly used in the treatment of
      movement disorders such as Parkinson disease (PD), dystonia, and other tremors.
      OBJECTIVE: To examine systematic errors in image-guided DBS electrode placement
      and to explore a calibration strategy for stereotactic targeting. METHODS: Pre-
      and postoperative stereotactic MR images were analyzed in 165 patients. The
      perpendicular error between planned target coordinates and electrode trajectory
      was calculated geometrically for all 312 DBS electrodes implanted. Improvement in
      motor unified PD rating scale III subscore was calculated for those patients with
      PD with at least 6 months of follow-up after bilateral subthalamic DBS. RESULTS:
      Mean (standard deviation) scalar error of all electrodes was 1.4(0.9) mm with a
      significant difference between left and right hemispheres. Targeting error was
      significantly higher for electrodes with coronal approach angle (ARC) >=10
      degrees  (P < .001). Mean vector error was X: -0.6, Y: -0.7, and Z: -0.4 mm
      (medial, posterior, and superior directions, respectively). Targeting error was
      significantly improved by using a systematic calibration strategy based on ARC
      and target hemisphere (mean: 0.6 mm, P < .001) for 47 electrodes implanted in 24
      patients. Retrospective theoretical calibration for all 312 electrodes would have
      reduced the mean (standard deviation) scalar error from 1.4(0.9) mm to 0.9(0.5)
      mm (36% improvement). With calibration, 97% of all electrodes would be within 2
      mm of the intended target as opposed to 81% before calibration. There was no
      significant correlation between the degree of error and clinical outcome from
      bilateral subthalamic nucleus DBS (R = 0.07). CONCLUSION: After calibration of a
      systematic targeting error an MR image-guided stereotactic approach would be
      expected to deliver 97% of all electrodes to within 2 mm of the intended target
      point with a single brain pass.

PMID- 21099571
TI  - Circumferential watertight dural repair using nitinol U-clips in expanded
      endonasal and sublabial approaches to the cranial base.
AB  - BACKGROUND: In recent years, significant advances have been made in the field of
      expanded endonasal approaches that permit treatment of different cranial base
      intradural lesions. OBJECTIVE: To report our technique of cranial base dural
      repair by the application of nitinol U-Clips in endoscope-assisted extended
      endonasal or sublabial approaches. Closure techniques and postoperative
      cerebrospinal (CSF) leaks are reported. METHODS: We reviewed 11 patients with
      different kinds of cranial base tumors or vascular diseases (2 tuberculum sellae
      meningiomas, 1 planum sphenoidale meningioma, 4 craniopharyngiomas, 1 recurrent
      clival chordoma, 1 esthesioneuroblastoma, 1 ethmoidal melanoma metastasis, 1
      basilar trunk aneurysm) who underwent an endoscope-assisted extended endonasal or
      sublabial approach. Dural repair was performed using nitinol U-Clips to
      circumferentially suture AlloDerm or fascia lata directly to the existing dural
      borders. Lumbar drainage was not used in 9 patients and was used in 2 patients
      for 5 days. Patients were evaluated for the appearance of CSF leaks. RESULTS:
      Postoperative CSF leak was observed in 1 patient (9%). This required a second
      transnasal repair. CONCLUSION: Circumferential dural closure with U-Clips is a
      useful adjunct to prevent CSF leaks after expanded endonasal or sublabial
      approaches to the cranial base for treatment of intracranial pathology.

PMID- 21099572
TI  - Revision of vagal nerve stimulator electrodes through a posterior cervical
      triangle approach: technical note.
AB  - BACKGROUND: We describe an approach to vagal nerve stimulator (VNS) lead
      replacement through the posterior cervical triangle. Scar around the structures
      of the carotid sheath is avoided and new leads are placed on a pristine section
      of the vagus nerve proximal to the original site. CLINICAL PRESENTATION: Skin
      incision from the implantation surgery is incorporated and extended to allow
      access to the posterior border of the sternocleidomastoid muscle (SCM).
      Dissection proceeds along the posterior border of the SCM. The SCM and jugular
      vein are retracted anterior to expose a fresh segment of the vagal nerve
      immediately superficial to the carotid artery and proximal to the original
      electrode site. Once the nerve is adequately exposed, electrode placement
      proceeds in the standard fashion. Dysfunctional electrodes are left in place, and
      the lead wire is cut as near the electrodes as can be easily accessed. Three
      patients have undergone lead revision with this approach. Lead placement was
      successful and free from complications in all cases. CONCLUSION: The posterior
      cervical triangle approach provides a virgin dissection plane for VNS revision.

PMID- 21099573
TI  - Transient adenosine-induced asystole during the surgical treatment of anterior
      circulation cerebral aneurysms: technical note.
AB  - BACKGROUND: Transient adenosine-induced asystole is a reliable method for
      producing a short period of relative hypotension during surgical and endovascular
      procedures. Although the technique has been described in the endovascular
      treatment of brain arteriovenous malformations, aortic aneurysms, and posterior
      circulation cerebral aneurysms, little description of its use in anterior
      circulation aneurysms is available. OBJECTIVE: To assess the benefits of
      adenosine-induced transient asystole in complex anterior circulation aneurysms,
      to describe our experience in selected cases, and to provide the first experience
      of the use of adenosine in anterior circulation aneurysms. METHODS: The adenosine
      induced cardiac arrest protocol allows us to titrate the duration of cardiac
      arrest on the basis of individual patient responses. The operative setup is the
      same as with all aneurysm clippings, with the addition of the placement of
      transcutaneous pacemakers as a precaution for prolonged bradycardia or asystole.
      Escalating doses of adenosine are given to determine the approximate dose that
      results in 30 seconds of asystole. When requested by the surgeon, the dose of
      adenosine is administered for definitive dissection and clipping. We present 6
      cases in which this technique was used. RESULTS: The use of transient adenosine
      induced asystole provided excellent circumferential visualization of the aneurysm
      neck and safe clip application. All patients did well neurologically and suffered
      no evidence of perioperative cerebral ischemia or delayed complication from the
      use of adenosine itself. CONCLUSION: Transient adenosine-induced asystole is a
      safe and effective technique in select circumstances that may aid in safe and
      effective aneurysm clipping. Along with the traditional techniques of brain
      relaxation, skull base approaches, and temporary clipping, adenosine-induced
      asystole facilitates circumferential visualization of the aneurysm neck and is
      another technique available to cerebrovascular surgeons.

PMID- 21099574
TI  - Operative nuances of side-to-side in situ posterior inferior cerebellar artery
      posterior inferior cerebellar artery bypass procedure.
AB  - BACKGROUND: An intracranial posterior circulation revascularization procedure in
      the form of a side-to-side in situ posterior inferior cerebellar artery (PICA)
      PICA bypass operation was introduced in 1991. This elegant and apparently low
      risk operation is performed infrequently. Thus, the operative nuances used in
      this procedure have not been well reported, limiting the scope of treatment
      modalities of vertebral artery-PICA aneurysms and vertebral dissections.
      OBJECTIVE: To repair an incidental right-sided PICA aneurysm noted in a 51-year
      old woman in magnetic resonance imaging and subsequent angiography. METHODS: The
      patient underwent side-to-side in situ PICA-PICA bypass surgery. RESULTS:
      Immediate indocyanine green angiography suggested that the PICA distal to the
      aneurysms was filling in a retrograde fashion through the bypass. On the
      following day, the patient was taken for coil embolization of the aneurysm.
      However, angiography images revealed that the aneurysm was spontaneously
      thrombosed, the proximal PICA was patent, and the PICA distal to the aneurysms
      was filling in a retrograde fashion, as suspected in intraoperative indocyanine
      green angiography. No further treatments were done. The patient recovered fully.
      CONCLUSION: We describe in detail the preoperative evaluation, decision process,
      and operative techniques for a side-to-side in situ PICA-PICA bypass operation,
      which is a relatively safe and elegant posterior circulation bypass procedure.

PMID- 21099575
TI  - Vidian nerve transposition for endoscopic endonasal middle fossa approaches.
AB  - BACKGROUND: The vidian nerve is a landmark for safe identification of the petrous
      internal carotid artery during endonasal endoscopic approaches (EEAs) to the
      skull base. The surgical technique classically described involves sacrifice of
      the nerve. OBJECTIVE: To demonstrate the feasibility of vidian nerve
      transposition during EEA. METHODS: After exposure of the vidian canal aperture,
      the bone is removed along its inferior and medial aspect. Once the depth is
      understood, determining the position of the internal carotid artery, the bone
      superior to the vidian nerve is drilled. The vidian nerve can then be transposed
      from its canal and retracted superiorly, allowing the drill to come inferiorly
      and to remove the bone lateral to the nerve, finalizing freedom around the vidian
      nerve. RESULTS: Four patients underwent EEA with vidian transposition. CASE
      ILLUSTRATION: a 20-year-old woman presented with partial numbness on the left
      side of the face and some tingling in the face, particularly inside her mouth.
      Magnetic resonance imaging scans demonstrated a Meckel cave tumor compatible with
      a left-side trigeminal schwannoma. EEA to the Meckel cave was performed and the
      vidian nerve was transposed. The tumor was totally resected and the vidian nerve
      preserved. The patient was discharged home in 2 days, stating improvement in
      facial sensation without new neurological deficits and denying dry eye. The
      patient was asymptomatic at the 9-month follow-up. None of the 4 patients who
      underwent this procedure complained of dry eye during the postoperative period.
      CONCLUSION: The vidian nerve transposition for EEAs to the skull base is an
      alternative technique that is feasible and conservative. It seems to be a good
      option that could prove beneficial to the quality of life of patients after
      surgery.

PMID- 21099576
TI  - Corticotomy closure avoids subdural collections after hemispherotomy.
AB  - BACKGROUND: Subdural collection is a possible adverse event that can occur after
      hemispherotomy. OBJECTIVE: : We describe our surgical technique to avoid subdural
      collection after peri-insular hemispherotomy in children. METHODS: Since 2008, we
      have closed the corticotomy with interrupted pial sutures and fibrinogen glue in
      16 patients. RESULTS: This operative technique stopped the occurrence of
      postoperative subdural collection and was not associated with an increased
      incidence of postoperative hydrocephalus. CONCLUSION: We recommend closing
      ventricular access after functional hemispherotomy, notably in patients who have
      had a stroke.

PMID- 21099577
TI  - Operative and technical complications of vagus nerve stimulator implantation.
AB  - BACKGROUND: The treatment of refractory epilepsy by vagus nerve stimulation (VNS)
      is a well-established therapy option for patients not suitable for epilepsy
      surgery and therapy refractory depressions. OBJECTIVE: To analyze surgical and
      technical complications after implantation of left-sided VNS in patients with
      therapy-refractory epilepsy and depression. METHODS: One hundred five patients
      receiving a VNS or VNS-related operations (n = 118) from 1999 to 2008 were
      investigated retrospectively. RESULTS: At the time of operation, 84 patients were
      younger than 18 years, with a mean age of 10.5 years. Twenty (19%) patients had
      technical problems or complications. In 6 (5.7%) patients these problems were
      caused by the operation. The device was removed in 8 cases. The range of
      surgically and technically induced complications included electrode fractures,
      early and late onset of deep wound infections, transient vocal cord palsy,
      cardiac arrhythmia under test stimulation, electrode malfunction, and
      posttraumatic dysfunction of the stimulator. CONCLUSION: VNS therapy is combined
      with a wide spread of possible complications. Technical problems are to be
      expected, including electrode fracture, dislocation, and generator malfunction.
      The major complication in younger patients is the electrode fracture, which might
      be induced by growth during adolescence. Surgically induced complications of VNS
      implantation are comparably low. Cardiac symptoms and recurrent nerve palsy need
      to be taken into consideration.

PMID- 21099578
TI  - Retrograde trans-posterior communicating artery snare-assisted rescue of lost
      access to a foreshortened pipeline embolization device: complication management.
AB  - BACKGROUND AND IMPORTANCE: The Pipeline embolization device (PED; Covidien
      Vascular Therapies, Mansfield, Massachusetts) is a promising, yet experimental,
      vascular reconstruction device for the treatment of complex intracranial
      aneurysms. We present a PED-related complication and describe a salvage strategy.
      CLINICAL PRESENTATION: A 64-year-old woman underwent PED-assisted parent vessel
      reconstruction for her giant cavernous internal carotid artery (ICA) aneurysm.
      During placement of the first PED, the proximal part of the PED foreshortened and
      was displaced into the aneurysm sac. Multiple subsequent attempts to
      recatheterize the PED failed, and, ultimately, distal access through and beyond
      the PED was lost. Therefore, completion of the Pipeline construct by stacking
      PEDs for definitive treatment was prevented. Retrograde access of the PED was
      gained from the distal ICA through a microwire that was advanced from the basilar
      artery through the posterior communicating artery. The microwire from the distal
      ICA was grasped with a snare from the proximal ICA and pulled down to the
      cervical ICA. The opened snare around the microwire was used as a lasso to
      advance a microcatheter from the cervical ICA through the PED to regain distal
      access. Five more PEDs were used to achieve complete parent vessel reconstruction
      and aneurysm obliteration. CONCLUSION: Maintaining distal access is critical
      until the entire parent vessel is reconstructed, especially when multiple PEDs
      are required. The salvage technique described may help regain distal access if it
      is lost during the procedure.

PMID- 21099579
TI  - Abciximab treatment modalities for thromboembolic events related to aneurysm
      coiling.
AB  - BACKGROUND: Thromboembolic complications are the most common cause of
      periprocedural morbidity associated with the endovascular treatment of
      intracranial aneurysms with detachable coils. OBJECTIVE: To estimate the safety
      and efficacy of using combined intra-arterial and intravenous abciximab to treat
      thrombi complicating endovascular cerebral aneurysm coil embolization. METHODS:
      In a retrospective analysis of 390 aneurysmal coiling procedures, we identified
      39 patients (10.0%) with thromboembolic events related to the procedure. As the
      first line of treatment in 23 of these patients, abciximab was administered intra
      arterially as a bolus followed by intravenous infusion over a 12-hour period.
      Eleven of the 23 patients were treated for ruptured aneurysms, 9 for unruptured
      aneurysms, and 3 for aneurysmal recanalization. Flow restoration and neurological
      outcome were evaluated. RESULTS: Amelioration as measured by the Thrombolysis in
      Myocardial Infarction flow grade score was achieved in 17 of 23 patients (73.9%),
      and no change was observed in 6 of 23 patients (26.1%). Complete recanalization
      was achieved in 13 patients (56.5%). A greater response to abciximab was noted
      for thrombi at the coil-parent artery interface, and a lesser response was noted
      for distal thrombi. No hemorrhagic complications were noted for any of the
      patients, whereas 11 patients (47.8%) showed ischemic lesions. A modified Rankin
      Scale score of 2 or less was achieved in 17 of 23 patients (73.9%), whereas 6 of
      23 patients (26.1%) had a modified Rankin Scale score of more than 2. CONCLUSION:
      Combined intra-arterial/intravenous administration of abciximab is safe and
      effective for treating thromboembolic complications that occur during aneurysmal
      coil embolization with no hemorrhagic complications.

PMID- 21099580
TI  - Petrous bone pneumatization is a risk factor for cerebrospinal fluid fistula
      following vestibular schwannoma surgery.
AB  - BACKGROUND: For the prevention of postoperative CSF fistula a better
      understanding of origins and risk factors is necessary. OBJECTIVE: To identify
      the petrous bone air cell volume as a risk factor for developing CSF fistula, we
      performed a retrospective analysis. METHODS: From 2000 to 2007 519 patients had a
      retrosigmoidal surgical removal of a vestibular schwannoma. The 22 who had a
      postoperative CSF fistula were chosen for evaluation in addition to 78 patients
      who were randomly selected in 4 equally sized cohorts: male/female with
      small/large tumors. Preoperative CT scans were analyzed regarding petrous bone
      air cell volume, area of visible pneumatization at the level of the internal
      auditory canal (IAC), tumor grade, and sex. RESULTS: : Women developed nearly
      half as many CSF fistulas (2.7%) as men (5.2%). The mean volume of the petrous
      bone air cells was 10.97 mL (SD, 4.9; range, 1.38-27.25). It was significantly
      lower for women (mean, 9.23 mL; SD, 3.8) than for men (mean, 12.5 mL; SD, 5.28; P
      = .0008). The mean air cell volume of CSF-fistula patients was 13.72 mL (SD,
      5.22). The difference concerning the air cell volume between patients who
      developed CSF fistulas and patients from the control group was significant (P =
      .0042). There was a significant positive correlation between the air cell volume
      and the area of pneumatization in one CT slide at the level of the IAC.
      CONCLUSION: The higher incidence of CSF fistulas in men compared with women can
      be explained by means of differently pneumatized petrous bones. A high amount of
      petrous bone pneumatization has to be considered as a risk factor for the
      development of postoperative CSF fistula after vestibular schwannoma surgery.

PMID- 21099581
TI  - A surgical case of delayed coil migration after balloon-assisted embolization of
      an intracranial broad-neck aneurysm: case report.
AB  - BACKGROUND AND IMPORTANCE: Balloon-assisted coil placement is an important
      technique for coil embolization of broad-neck aneurysms. With this technique, we
      can prevent coil migration into a parent artery during a procedure. Complications
      of intraprocedural coil migration have been reported in the literature. However,
      delayed coil migration is extremely rare. We present a case of delayed coil
      migration after balloon-assisted coil embolization and describe our management of
      this complication. CLINICAL PRESENTATION: A 59-year-old man presented with
      hypertension and a tension headache. Clinical evaluation incidentally discovered
      an unruptured broad-neck aneurysm at the left internal carotid bifurcation.
      Endovascular embolization of the aneurysm was performed with a balloon-assisted
      technique. The patient had a transient ischemic attack, and a skull radiograph
      showed coil migration 3 months after the procedure. We performed an operation to
      remove the coils and to clip the aneurysm with superficial temporal artery and
      middle cerebral artery bypass. The patient was discharged without neurological
      deficit. CONCLUSION: This is a rare case in which delayed coil migration into the
      parent artery occurred after balloon-assisted coil embolization, highlighting the
      importance of surgical management of delayed coil migration.

PMID- 21099582
TI  - Endoscopic transsphenoidal, transclival resection of an enterogenous cyst located
      ventral to the brainstem: case report.
AB  - BACKGROUND AND IMPORTANCE: Enterogenous cysts are rare tumors found most commonly
      in the spine, but they have also been reported intracranially. Cases of
      enterogenous cysts located within the posterior fossa have traditionally been
      resected via difficult craniotomies that require prolonged retraction and risk
      injury to cranial nerves. We describe a method for resection of an enterogenous
      cyst located anterior to the brainstem via the endoscopic transsphenoidal
      approach. CLINICAL PRESENTATION: A 37-year-old man was found to have a 2-cm mass
      anterior to the brainstem during routine screening after a trauma. The mass was
      located within the prepontine cistern, enhanced with gadolinium contrast, and
      showed no restrictive diffusion. This lesion was most consistent with an
      enterogenous cyst. A minimally invasive endoscopic endonasal transsphenoidal
      transclival approach was performed for gross total resection of the tumor.
      CONCLUSION: We discuss the endoscopic transsphenoidal approach used for the
      resection of an enterogenous cyst in the posterior fossa anterior to the
      brainstem. The transsphenoidal approach provides direct access to lesions in this
      location using a minimally invasive technique while avoiding excessive brain
      retraction or injury to cranial nerves. In addition, we provide an updated review
      of the literature for enterogenous cysts located within the posterior fossa.

PMID- 21099583
TI  - Targeted extracranial-intracranial bypass with intra-aneurysmal administration of
      indocyanine green: case report.
AB  - BACKGROUND AND IMPORTANCE: Early origin of the middle cerebral artery M2 segment
      is a normal variant. When such a vessel is occluded proximally, the parenchyma
      distal to the vessel may become ischemic. Targeted extracranial to intracranial
      bypass to such a specific branch may preserve perfusion to the end organ. We
      describe the use of intra-aneurysmal injection of indocyanine green to identify a
      target middle cerebral artery branch (MCA) for bypass, immediately followed by
      proximal parent vessel sacrifice via endovascular embolization. CLINICAL
      PRESENTATION: A 45-year-old woman presented to an outside hospital with
      headaches. Magnetic resonance imaging revealed a giant aneurysm of the right MCA.
      The aneurysm gave rise to an M2 branch that supplied the right anterior frontal
      operculum, as well as the anterolateral portion of the superior temporal gyri.
      Balloon test occlusion was nondiagnostic because of the territory involved, and
      the risk of sizable infarction after vessel sacrifice was thought to be high.
      Craniotomy and targeted extracranial to intracranial bypass to an M4 opercular
      branch was performed with intra-aneurysmal injection of indocyanine green. In our
      combined endovascular/open cerebrovascular suite, an opercular MCA branch that
      fluoresced during the first-pass arterial circulation of indocyanine green was
      identified, and a superficial temporal artery to MCA bypass was performed.
      Angiographic verification of bypass patency was confirmed, followed by embolic
      occlusion of the giant aneurysm with preservation of flow to the parenchyma at
      risk through the bypass. CONCLUSION: Targeted bypass to distal branches is
      feasible with intra-arterial and intra-aneurysmal injection of indocyanine green,
      allowing confident preservation of blood supply to areas distal to the sacrificed
      vessel.

PMID- 21099586
TI  - Striving for excellence.

PMID- 21099587
TI  - Ulisprisal acetate: a novel molecule and 5-day emergency contraceptive.

PMID- 21099588
TI  - Malpractice reform--opportunities for leadership by health care institutions and
      liability insurers.

PMID- 21099589
TI  - Pelvic examinations and access to oral hormonal contraception.
AB  - OBJECTIVE: Requiring a pelvic examination before prescribing oral contraception
      poses an unnecessary barrier to contraceptive access. Medical guidelines have
      outlined the safety of oral contraception provision without a pelvic examination,
      yet little is known about the practices of clinicians providing reproductive
      health care. Our purpose was to investigate clinicians' requirements for pelvic
      examination and what may account for practice differences. METHODS: We
      administered a mailed survey to a national probability sample of obstetrician
      gynecologists (ob-gyns), family medicine physicians, and advanced practice nurses
      specializing in obstetrics and gynecology and women's health or family medicine
      in 2008-2009 (N=1,196), with a response rate of 65.3%. RESULTS: Nearly one third
      of ob-gyns and family medicine physicians reported always requiring a pelvic
      examination when prescribing oral contraception (ob-gyns 29%; family medicine
      33%). A higher proportion of advanced practice nurses in primary care (45%) and a
      markedly lower percentage of advanced practice nurses in reproductive health
      (17%) reported always requiring the examination. In adjusted analyses, older
      clinicians were more likely to require the pelvic examination (odds ratio [OR]
      1.03, P<.01) and clinicians serving a higher proportion of Medicaid patients more
      likely (OR 1.62, P<.05). Providers in private practice were more than twice as
      likely as those working in family-planning or community clinics to require pelvic
      examinations (OR 2.30, P<.01). CONCLUSION: One third of clinicians we surveyed
      require pelvic examinations before provision of oral contraceptives, despite
      guidelines indicating they are unnecessary and research suggesting they can pose
      a barrier to contraceptive access.

PMID- 21099591
TI  - Self-perception of weight and its association with weight-related behaviors in
      young, reproductive-aged women.
AB  - OBJECTIVES: To examine weight misperceptions and their predictors and association
      with weight-related behaviors among low-income, multiethnic, reproductive-age
      women. METHODS: We assessed perceptions of body weight and weight-related
      behaviors of women aged 18 to 25 attending one of five publicly funded
      reproductive clinics in Texas between August 2008 and March 2010. Data were
      collected through self-administered questionnaires and chart review. Overweight
      and normal-weight women were divided into four categories based on self
      perception of their body weight: overweight misperceivers, overweight actual
      perceivers, normal-weight misperceivers, and normal-weight actual perceivers.
      Multivariable logistic regression analyses were performed to examine the
      predictors of misperception and the association with weight-related behaviors.
      RESULTS: Twenty-three percent (267/1,162) of overweight and 16% (170/1,062) of
      normal-weight women were misperceivers. Overweight African-American women were
      more likely to consider themselves normal weight (28% compared with 15%; odds
      ratio [OR], 2.84; 95% confidence interval [CI], 1.79-4.50), whereas normal-weight
      African-American women were less likely than whites to consider themselves
      overweight (7% compared with 16%; OR 0.40; 95% CI 0.22-0.74). Overweight women
      who had at least some college education (14% compared with 29%; OR 0.53; 95% CI
      0.32-0.86) and used the Internet (18% compared with 28%; OR 0.47; 95% CI 0.31
      0.70) were less likely to misperceive their body weight. Normal-weight
      misperceivers were more likely to report healthy and unhealthy weight-reduction
      behaviors compared with normal-weight actual perceivers, after adjusting for age,
      race, ethnicity, and body mass index. Opposite scenarios were observed for
      overweight misperceivers. CONCLUSION: Weight misperception is common among both
      overweight and normal-weight women of reproductive age. Clinicians should provide
      patient-specific counseling related to healthy weight management goals that take
      each patient's perceptions into consideration.

PMID- 21099590
TI  - Contraceptive efficacy, acceptability, and safety of C31G and nonoxynol-9
      spermicidal gels: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether a gel containing the spermicide C31G was
      noninferior to a commercially available product containing nonoxynol-9. METHODS:
      Participants were healthy, sexually active women aged 18-40 years. Measured
      outcomes included pregnancy rates, continuation rates, adverse events, and
      acceptability. The primary study outcome was contraceptive efficacy. Sample size
      was calculated at a 2.5% significance level using a one-sided test based on
      assumed 6-month pregnancy probability of 15% in the nonoxynol-9 group. Sample
      size was sufficient to reject, with 80% power, the null hypothesis that pregnancy
      probability in the C31G arm would be more than 5% higher. RESULTS: Nine hundred
      thirty-two women were randomized in the C31G group and 633 in the nonoxynol-9
      group. For randomized patients with at least one episode of coitus (modified
      intent-to-treat group), 6-month pregnancy probabilities were 12.0% (95%
      confidence interval [CI] 9.3-14.7%) and 12.0% (95% CI 8.7-15.3%) for C31G and
      nonoxynol-9,respectively. Twelve-month pregnancy probabilities were 13.8% (95% CI
      7.6-20%) for C31G and 19.8% (95% CI 10.9-28.7%) for nonoxynol-9. Two serious
      adverse events were deemed possibly related to study product and neither occurred
      in the C31G group. Three fourths of users in either group reported that they
      liked their assigned study product. Approximately 40% of patients discontinued
      prematurely for reasons other than pregnancy with 11% lost to follow-up.
      CONCLUSION: C31G demonstrated noninferior contraceptive efficacy compared with
      nonoxynol-9. C31G may provide another marketable option for women seeking
      spermicidal contraception. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.ClinicalTrials.gov, NCT00274261.

PMID- 21099592
TI  - Contemporary patterns of spontaneous labor with normal neonatal outcomes.
AB  - OBJECTIVE: To use contemporary labor data to examine the labor patterns in a
      large, modern obstetric population in the United States. METHODS: Data were from
      the Consortium on Safe Labor, a multicenter retrospective study that abstracted
      detailed labor and delivery information from electronic medical records in 19
      hospitals across the United States. A total of 62,415 parturients were selected
      who had a singleton term gestation, spontaneous onset of labor, vertex
      presentation, vaginal delivery, and a normal perinatal outcome. A repeated
      measures analysis was used to construct average labor curves by parity. An
      interval-censored regression was used to estimate duration of labor, stratified
      by cervical dilation at admission and centimeter by centimeter. RESULTS: Labor
      may take more than 6 hours to progress from 4 to 5 cm and more than 3 hours to
      progress from 5 to 6 cm of dilation. Nulliparous and multiparous women appeared
      to progress at a similar pace before 6 cm. However, after 6 cm, labor accelerated
      much faster in multiparous than in nulliparous women. The 95 percentiles of the
      second stage of labor in nulliparous women with and without epidural analgesia
      were 3.6 and 2.8 hours, respectively. A partogram for nulliparous women is
      proposed. CONCLUSION: In a large, contemporary population, the rate of cervical
      dilation accelerated after 6 cm, and progress from 4 cm to 6 cm was far slower
      than previously described. Allowing labor to continue for a longer period before
      6 cm of cervical dilation may reduce the rate of intrapartum and subsequent
      repeat cesarean deliveries in the United States.

PMID- 21099593
TI  - Neonatal outcomes after demonstrated fetal lung maturity before 39 weeks of
      gestation.
AB  - OBJECTIVE: To compare outcomes among neonates delivered after documentation of
      fetal lung maturity before 39 weeks and those delivered at 39 or 40 weeks.
      METHODS: This was a retrospective cohort study of women with singleton pregnancy
      delivered at 36 0/7 to 38 6/7 weeks after positive fetal lung maturity testing
      (based on amniotic fluid lecithin to sphingomyelin ratio) or at 39 0/7 to 40 6/7
      weeks (without maturity testing) at our center from 1999 to 2008. Women with
      fetuses with major congenital anomalies, cord prolapse, nonreassuring antepartum
      testing, placental abruption, or oligohydramnios were excluded. A primary
      composite neonatal outcome included death, adverse respiratory outcomes,
      hypoglycemia, treated hyperbilirubinemia, generalized seizures, necrotizing
      enterocolitis, hypoxic ischemic encephalopathy, periventricular leukomalacia, and
      suspected or proven sepsis. RESULTS: There were 459 neonates delivered at 36 to
      38 weeks and 13,339 delivered at 39 to 40 weeks; mean birth weight was 3,107+/
      548 g and 3,362+/-439 g, respectively. The risk of the composite adverse neonatal
      outcome was 6.1% for the 36- to 38-week group compared with 2.5% for the 39- to
      40-week group (relative risk 2.4; confidence interval [CI] 1.7-3.5). After
      multivariable adjustment, early delivery remained significantly associated with
      an increased risk of the composite outcome (adjusted odds ratio [OR]1.7; CI 1.1
      2.6) as well as several individual outcomes, including respiratory distress
      syndrome (adjusted OR 7.6; CI 2.2-26.6), treated hyperbilirubinemia (adjusted OR
      11.2; CI 3.6-34), and hypoglycemia (adjusted OR 5.8; CI 2.4-14.3). CONCLUSION:
      Neonates delivered at 36 to 38 weeks after confirmed fetal lung maturity are at
      higher risk of adverse outcomes than those delivered at 39 to 40 weeks.

PMID- 21099594
TI  - Correlation between stillbirth vital statistics and medical records.
AB  - OBJECTIVE: Most data regarding conditions associated with or contributing to
      stillbirth are derived from fetal death certificates. Our purposes were to
      compare stillbirth data recorded in vital statistics with those in the medical
      record and to investigate whether diagnostic evaluations differed in tertiary
      care and community hospitals. METHODS: In this cross-sectional study, fetal death
      certificate data identified individuals with stillbirths delivering in eight Salt
      Lake City hospitals from 1998 to 2002. Medical records were reviewed to assess
      demographics, diagnostic evaluation, and potential causes of stillbirth. Data
      were compared between death certificates and the medical record by calculation of
      the kappa coefficient for categorical variables or Kendall's tau-b coefficients
      based on the number of concordant and discordant pairs of observations for
      continuous variables. Diagnostic tests completed were compared between community
      and tertiary care hospitals with chi or Fisher exact test. RESULTS: Five-hundred
      fifty-six individuals were identified, and 461 (83%) charts were available for
      review. Correlation between death certificates and the medical record was nearly
      perfect for demographic variables (correlation 0.8-0.9) but slight to moderate
      (correlation 0.2-0.5) for contributing or etiologic factors. Important diagnostic
      tests performed significantly more often in tertiary care than community
      hospitals included autopsy (35% compared with 13%, P<.01), karyotype (17%
      compared with 4%, P<.01), Kleihauer-Betke (22% compared with 13%, P=.01),
      toxicology screen (13% compared with 2%, P<.01), and complete blood count (95%
      compared with 90%, P=.03). CONCLUSION: There are important discrepancies between
      fetal death certificates and medical records. Complete work-up, review of the
      medical record, and efforts to increase accurate reporting may improve the
      accuracy of stillbirth vital statistics. Diagnostic evaluation was more extensive
      in tertiary care hospitals.

PMID- 21099595
TI  - Pregnancy-related mortality in the United States, 1998 to 2005.
AB  - OBJECTIVE: To estimate the risk of women dying from pregnancy complications in
      the United States and to examine the risk factors for and changes in the medical
      causes of these deaths. METHODS: De-identified copies of death certificates for
      women who died during or within 1 year of pregnancy and matching birth or fetal
      death certificates for 1998 through 2005 were received by the Pregnancy Mortality
      Surveillance System from the 50 states, New York City, and Washington, DC. Causes
      of death and factors associated with them were identified, and pregnancy-related
      mortality ratios (pregnancy-related deaths per 100,000 live births) were
      calculated. RESULTS: The aggregate pregnancy-related mortality ratio for the 8
      year period was 14.5 per 100,000 live births, which is higher than any period in
      the previous 20 years of the Pregnancy Mortality Surveillance System. African
      American women continued to have a three- to four-fold higher risk of pregnancy
      related death. The proportion of deaths attributable to hemorrhage and
      hypertensive disorders declined from previous years, whereas the proportion from
      medical conditions, particularly cardiovascular, increased. Seven causes of death
      -hemorrhage, thrombotic pulmonary embolism, infection, hypertensive disorders of
      pregnancy, cardiomyopathy, cardiovascular conditions, and noncardiovascular
      medical conditions--each contributed 10% to 13% of deaths. CONCLUSION: The
      reasons for the reported increase in pregnancy-related mortality are unclear;
      possible factors include an increase in the risk of women dying, changed coding
      with the International Classification of Diseases, 10th Revision, and the
      addition by states of pregnancy checkboxes to the death certificate. State-based
      maternal death reviews and maternal quality collaboratives have the potential to
      identify deaths, review the factors associated with them, and take action on the
      findings.

PMID- 21099597
TI  - 2009 cervical cytology guidelines and chlamydia testing among sexually active
      young women.
AB  - OBJECTIVE: An American College of Obstetricians and Gynecologists Practice
      Bulletin published in 2009 recommended that cervical cancer screening should
      begin at age 21 years and women younger than 30 years should be rescreened every
      2 years rather than annually. The purpose of this study is to estimate the effect
      that decreased frequency of cervical cancer screening would have on chlamydia
      screening, which is recommended annually for sexually active women aged 25 years
      or younger. METHODS: Using an administrative database of medical claims from
      commercially insured girls and women, we compared annual chlamydia screening
      rates of sexually active adolescent girls and young women aged 15 to 25 years in
      2007 among those who underwent cervical cancer screening and those who were not
      screened for cervical cancer. RESULTS: We identified 701,193 sexually active
      adolescent girls and young women aged 15 to 25 years. Chlamydia screening rates
      were significantly higher among adolescent girls and young women who underwent
      cervical cancer screening compared with those who did not: 43.6% compared with
      9.5% for adolescent girls and young women aged 15 to 20 years and 36.1% compared
      with 12.2% for women aged 21 to 25 years. Among adolescent girls and young women
      identified as sexually active in 2007, 90.5% had visits for reproductive health
      services other than cervical cancer screening that could provide opportunities
      for chlamydia screening. CONCLUSION: Although the revised American College of
      Obstetricians and Gynecologists Practice Bulletin recommending less frequent
      cervical cancer screening will likely reduce chlamydia screening rates in
      adolescent girls and young women, health care providers should be aware of other
      opportunities for chlamydial testing. Options include patient self-collected
      vaginal swabs and urine specimens collected during visits at which adolescent
      girls and young women seek other reproductive health or preventive services.

PMID- 21099598
TI  - Colposcopy prediction of progression in human papillomavirus infections with
      minor cervical lesions.
AB  - OBJECTIVES: To evaluate the risk of progression to cervical intraepithelial
      neoplasia (CIN) grade 2 or 3 in women with positive human papillomavirus (HPV)
      testing and low-grade (low-grade squamous intraepithelial lesions), borderline
      (atypical squamous cells of undetermined significance), or no cervical lesions,
      and to determine the accuracy of initial colposcopy to predict progression.
      METHODS: Women with HPV infection and low-grade squamous intraepithelial lesions,
      atypical squamous cells, or normal cytology were recruited and grouped according
      to cytologic or histologic diagnosis. Exclusion criteria were histologic CIN 2 or
      3, previous cervical cancer and HPV infection, cervical disease, or treatment for
      CIN 2 or 3 in the past 3 years. Four-hundred sixty-five women were included and
      monitored by cytology, Hybrid Capture-2 test, and colposcopy every 6 months.
      Colposcopy results were described as normal, with minor or major changes, and
      lesion size was recorded in quadrants. RESULTS: Forty-three women (9.3%) had
      progression to CIN 2 or 3. No significant differences were found in rate of
      progression between women with low-grade squamous intraepithelial lesions,
      atypical squamous cells, or negative results (8.2%, 13.4%, and 9.8%,
      respectively; P=.679). Neither colposcopy pattern (P=.284) nor lesion size
      (P=.170) at recruitment provided any information on the risk of progression.
      History of cervical lesion and worsening of the colposcopy pattern during follow
      up were associated with progression (P<.001). CONCLUSION: Initial colposcopy
      findings do not provide relevant information on the risk of progression in HPV
      positive women with minor or no cervical lesions. These women have a similar risk
      of progression and should benefit from the same follow-up strategies.

PMID- 21099596
TI  - Home compared with clinic-based screening for sexually transmitted infections: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine whether home-based screening for sexually transmitted
      infections results in a higher sexually transmitted infection screening rate
      compared with clinic-based screening in participants using long-acting reversible
      contraception. METHODS: We performed a randomized clinical trial of women using
      long-acting reversible contraception methods in the Contraceptive CHOICE Project
      (n=558). Participants were randomly assigned to home-based testing (swabs mailed
      to the participant's home) or clinic-based testing. Self-collected vaginal swabs
      were tested for Chlamydia trachomatis and Neisseria gonorrhoeae using strand
      displacement analysis. We estimated the relative risk (RR) of screening by group
      using Poisson regression with robust error variance. RESULTS: The randomization
      groups were similar at baseline, except for marital status; the clinic group had
      more never-married women (62.0% compared with 51.6%), and the home group had more
      divorced women (12.1% compared with 5.6%, P=.007). Women in the home group were
      more likely to self-report screening compared with women in the clinic group in
      the multivariable analysis (56.3% compared with 32.9%; RR 1.7; 95% confidence
      interval [CI] 1.4-2.0). When analyzed by tests received or documented in medical
      records, similar results were obtained (56.3% compared with 25.0%; RR 2.2; 95% CI
      1.7-2.7). Women who completed screening had higher levels of education and were
      more likely to receive public assistance compared with those who did not complete
      screening. CONCLUSION: Long-acting reversible contraception users randomized to
      sexually transmitted infection screening at home were more likely to complete
      screening than those randomized to traditional clinic-based screening. Home-based
      screening may be useful in women using long-acting reversible contraceptive
      methods who may not present for regular screening. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT01184157.

PMID- 21099599
TI  - Common abnormal results of pap and human papillomavirus cotesting: what
      physicians are recommending for management.
AB  - OBJECTIVE: To evaluate the association between physician and practice
      characteristics and adherence to management guidelines to better understand the
      factors associated with different screening recommendations by primary care
      physicians. METHODS: We used a cross-sectional nationally representative survey
      of 950 primary care physicians familiar with human papillomavirus (HPV) testing
      to assess adherence to management guidelines by analyzing responses to two
      clinical vignettes of a 35-year-old woman who had Pap and HPV tests results: 1)
      discordant (normal Pap and positive HPV) or 2) mildly abnormal (atypical squamous
      cells of undetermined significance Pap and negative HPV). Analyses included
      multivariable logistic regression. RESULTS: For the discordant test results,
      54.3% (95% confidence interval [CI] 51-57.6%) of physicians recommended both Pap
      and HPV testing in 6-12 months, adhering to management guidelines. For the mildly
      abnormal results, only 12.2% (95% CI 10-14.7%) had a guideline-adherent
      recommendation of Pap testing in 12 months with no HPV test. In multivariable
      analyses, no significant difference among physicians' specialties was observed
      for the discordant results. For the mildly abnormal results, physician specialty
      was associated with guideline adherence in which obstetrician-gynecologists had
      the highest percent of adherence (19.8%) compared with family and general
      practitioners (9.3%) and internists (11%) (P<.001). CONCLUSION: Even for the most
      common abnormal results, many physicians reported recommendations that did not
      adhere to current management guidelines. Evidence-based interventions are needed
      to improve adherence to management guidelines for the newer HPV DNA test.

PMID- 21099600
TI  - The effect of surgeon volume on outcomes and resource use for vaginal
      hysterectomy.
AB  - OBJECTIVE: To estimate the effect of surgical volume on outcomes and resource use
      in women undergoing vaginal hysterectomy. METHODS: Women who underwent total
      vaginal hysterectomy and were registered in the Perspective database were
      examined. Perspective is a nationwide database developed to measure quality and
      resource use. Procedure-associated intraoperative, perioperative, and
      postoperative medical complications as well as hospital readmission, length of
      stay, intensive care unit (ICU) use, operating time, and cost were analyzed.
      Based on the overall gynecologic surgical volume and vaginal surgical volume of
      their surgeons, patients were stratified into tertiles. Complications were
      compared using adjusted generalized estimating equations and reported as odds
      ratios (ORs). RESULTS: A total of 77,109 patients operated on by 6,195
      gynecologic surgeons were identified. After adjustment for the effects of other
      demographic variables and concomitant procedures, patients operated on by high
      volume vaginal surgeons were 31% (OR 0.69; 95% confidence interval [CI] 0.59
      0.80) less likely to experience an operative injury, whereas perioperative
      complications were reduced by 19% (OR 0.81; 95% CI 0.72-0.92), medical
      complications decreased by 24% (OR 0.76; 95% CI 0.67-0.86), ICU admission reduced
      by 46% (OR 0.56; 95% CI 0.43-0.73), and the transfusion rate decreased by 28% (OR
      0.72; 95% CI 0.61-0.85) in patients treated by high-volume vaginal surgeons,
      whereas rates of readmission were higher (OR 1.24; 95% CI 1.04-1.47) in patients
      treated by high-volume surgeons. Operative times were lower in patients operated
      on by high-volume surgeons (P<.001). Although total gynecologic surgical volume
      had no effect on cost, patients treated by high-volume vaginal surgeons had lower
      costs (P<.001). CONCLUSION: Perioperative morbidity and resource use are lower in
      women undergoing vaginal hysterectomy when the procedure is performed by high
      volume vaginal surgeons.

PMID- 21099601
TI  - Appendiceal pathology at the time of oophorectomy for ovarian neoplasms.
AB  - OBJECTIVE: To investigate the prevalence of appendiceal pathology in women
      undergoing surgery for a suspected ovarian neoplasm and the predictive value of
      intraoperative findings to determine the need for appendectomy at the time of
      surgery. METHODS: Retrospective analysis of patients who underwent oophorectomy
      and appendectomy during the same surgical procedures at the University of
      Virginia Health System from 1992 to 2007. Observations were stratified based on
      the nature (benign, borderline, or malignant) and histology (serous compared with
      mucinous) of the ovarian neoplasm, frozen compared with final pathological
      diagnosis, and the gross appearance of the appendix. RESULTS: Among the 191
      patients identified, frozen section was consistent with seven mucinous and 35
      serous carcinomas, 16 serous and 33 mucinous borderline tumors, 71 mucinous and
      serous cystadenomas, and 29 cases of suspected metastatic tumor from a
      gastrointestinal primary. The highest rates of coexisting appendiceal pathology
      were associated with serous ovarian cancers (94.4% of grossly abnormal and 35.3%
      of normal appendices) and ovarian tumors suspected to be of primary
      gastrointestinal origin (83.3% grossly abnormal and 60.0% normal appendices
      harbored coexisting mucinous neoplasms). Linear regression analysis revealed that
      appearance of the appendix and frozen section diagnosis of the ovarian pathology
      were statistically significant predictors of coexisting appendiceal pathology,
      but the latter was more important. CONCLUSION: The prevalence of coexisting,
      clinically significant appendiceal pathology is low with a frozen section
      diagnosis of serous or mucinous cystadenoma. Appendectomy is recommended when
      frozen section diagnosis is mucinous or serous ovarian carcinoma, borderline
      tumor or metastatic carcinoma of suspected gastrointestinal origin.

PMID- 21099602
TI  - Laparoscopic conversion rate for uterine cancer surgical staging.
AB  - OBJECTIVE: To estimate the conversion rate of attempted laparoscopic staging for
      primary endometrial adenocarcinoma. METHODS: Two hundred thirty-five consecutive
      patients with primary endometrial adenocarcinoma underwent attempted laparoscopic
      staging regardless of age, body mass index (BMI, calculated as weight
      (kg)/[height (m)]2), uterine size, and prior surgery. No patients were excluded.
      RESULTS: Mean BMI was 39 (range, 22-77), and 85 patients (36%) had a BMI higher
      than 40 kg/m2. Mean blood loss was 162 mL (range, 25-1850 mL), mean operating
      room time was 2 hours (range, 1-4 hours 20 minutes), and mean hospital stay was 1
      day (range, 1-4 days). There were six conversions (3%) to laparotomy or vaginal
      hysterectomy, all occurring in patients with a BMI higher than 40; mean BMI of
      conversions was 66 (range, 55-77). CONCLUSION: Of 235 consecutive cases of
      attempted laparoscopic staging for primary endometrial adenocarcinoma, conversion
      to laparotomy or vaginal hysterectomy occurred in 3% of the total patients and 7%
      in patients with a BMI of 40 or higher.

PMID- 21099603
TI  - Primary malignant melanoma of the vagina.
AB  - OBJECTIVE: To describe the clinical and pathologic features of vaginal melanoma
      and to determine predictors of outcome in patients with this disease. METHODS:
      Thirty-seven women with clinical and radiographic stage I vaginal melanoma
      treated at one institution between 1980 and 2009 were included in this
      retrospective study. Treatment modalities were assigned to one of three
      categories: pelvic exenteration, wide excision, and nonsurgical (primary
      radiation therapy, chemotherapy, or both). Overall survival and progression-free
      survival were calculated from the date of the surgical diagnosis. RESULTS: The
      median age was 60.6 years. Eighty-four percent of patients were white. Vaginal
      bleeding was the most common presenting symptom. Lesions were located in the
      distal third of the vagina in the majority (65%) of patients. Initial management
      included a wide local or radical excision (76% of patients); pelvic exenteration
      (14%); and radiotherapy, chemotherapy, or radiotherapy and chemotherapy (10%). At
      a median follow-up of 17.4 months, 33 women experienced disease recurrence.
      Recurrence was local only in seven patients (22%), distant only in 20 (63%), and
      both in five (15%). The most common sites of distant recurrence were lungs and
      liver. Median progression-free survival was 11.4 months, and median overall
      survival was 19 months. The 5-year progression-free and overall survival rates
      were 9.5% and 20.0%, respectively. Patients treated surgically had significantly
      longer survival than those treated nonsurgically (P=.01). Radiotherapy after wide
      excision reduced local recurrence risk and increased survival from 16.1 months to
      29.4 months, although the increase was not significant (P=.46). CONCLUSION:
      Malignant vaginal melanoma, even when localized at presentation, has a very poor
      prognosis. Patients treated surgically have longer survival than those treated
      nonsurgically. Radiotherapy after wide excision reduces local but not distant
      recurrences.

PMID- 21099604
TI  - Projecting the need for gynecologic oncologists for the next 40 years.
AB  - OBJECTIVE: To estimate the ratio of gynecologic cancer cases to practicing
      gynecologic oncologists in the United States over the next 40 years. METHODS:
      Using population projections from the U.S. Census Bureau and incidence and
      mortality rates from Surveillance, Epidemiology and End Results surveys, we
      estimated the annual number of new gynecologic cancer cases through 2050; the
      effects of human papillomavirus (HPV) vaccination was included in cervical cancer
      estimates. The number of practicing gynecologic oncologists was projected through
      2050 using data from the 2005 Society of Gynecologic Oncologists Practice Survey,
      current Society of Gynecologic Oncologists membership information, American Board
      of Obstetrics and Gynecology and Gynecologic Oncology oral examination results,
      and mortality estimates from U.S. life tables. Projected time in practice was sex
      dependent based on Society of Gynecologic Oncologists Practice Survey. For
      sensitivity analyses, we varied annual number and sex distribution of fellowship
      graduates, HPV vaccination coverage rates, and future incidence of overweight and
      obesity. RESULTS: At constant training rates, the annual number of new cancer
      cases per practicing gynecologic oncologist will rise from 112 in 2010 to 133 in
      2050, a 19% increase. If the annual number of fellowship graduates increases by
      25%, the ratio of cancer cases per gynecologic oncologist will decrease to 106, a
      5% decrease. Projections are more sensitive to changes in physician demographics
      than to changes in HPV vaccination coverage rates. CONCLUSION: The gynecologic
      cancer caseload of practicing gynecologic oncologists will increase by almost 20%
      over the next 40 years at constant training rates. Changes in the projected sex
      distribution of fellowship graduates and their time in practice affect these
      projections.

PMID- 21099605
TI  - Rate of and risks for regression of cervical intraepithelial neoplasia 2 in
      adolescents and young women.
AB  - OBJECTIVE: To describe the natural history of cervical intraepithelial neoplasia
      (CIN) 2 in a prospective study of adolescents and young women, and to examine the
      behavioral and biologic factors associated with regression and progression.
      METHODS: Adolescents and women aged 13 to 24 years who were referred for abnormal
      cytology and were found to have CIN 2 on histology were evaluated at 4-month
      intervals. Risks for regression were defined as three consecutive negative
      cytology and histology visits, and progression to CIN 3 was estimated using Cox
      proportional hazards regression models. RESULTS: Ninety-five patients with a mean
      age of 20.4 years (+/-2.3) were entered into the analysis. Thirty-eight percent
      resolved by year 1, 63% resolved by year 2, and 68% resolved by year 3.
      Multivariable analysis found that recent Neisseria gonorrhoeae infection (hazard
      ratio 25.27; 95% confidence interval [CI] 3.11-205.42) and medroxyprogesterone
      acetate use (per month) (hazard ratio 1.02; 95% CI 1.003-1.04) were associated
      with regression. Factors associated with nonregression included combined hormonal
      contraception use (per month) (hazard ratio 0.85; 95% CI 0.75-0.97) and
      persistence of human papillomavirus (HPV) of any type (hazard ratio 0.40; 95% CI
      0.22-0.72). Fifteen percent of patients showed progression by year 3. HPV 16/18
      persistence (hazard ratio 25.27; 95% CI 2.65-241.2; P=.005) and HPV 16/18 status
      at last visit (hazard ratio 7.25; 95% CI 1.07-49.36; P<.05) were associated with
      progression Because of the small sample size, other covariates were not examined.
      CONCLUSION: The high regression rate of CIN 2 supports clinical observation of
      this lesion in adolescents and young women.

PMID- 21099606
TI  - The effect of preterm premature rupture of membranes on neonatal mortality rates.
AB  - OBJECTIVE: To estimate the effect of preterm premature rupture of membranes
      (PROM) on neonatal mortality. METHODS: A cross-sectional study using a state
      perinatal database (California Perinatal Quality Care Collaborative) was
      performed. Prenatal data, including ruptured membranes, corticosteroid
      administration, maternal age, maternal race, maternal hypertension, mode of
      delivery, and prenatal care, were recorded. Mortality rates were compared for
      neonates born between 24 and 34 weeks of gestation without preterm PROM to those
      with recent (less than 18 hours before delivery) and prolonged (more than 18
      hours before delivery) preterm PROM. Neonatal sepsis rates were also examined.
      RESULTS: Neonates born between 24 0/7 and 34 0/7 weeks of gestation from 127
      California neonatal intensive care units between 2005 and 2007 were included
      (N=17,501). When analyzed by 2-week gestational age groups, there were no
      differences in mortality rates between those born with and without membrane
      rupture before delivery. The presence of prolonged preterm PROM was associated
      with decreased mortality at 24 to 26 weeks of gestation (18% compared with 31%
      for recent preterm PROM; odds ratio [OR] 1.79; confidence interval [CI] 1.25
      2.56) but increased mortality at 28 to 30 weeks of gestation (4% compared with 3%
      for recent preterm PROM; OR 0.44; CI 0.22, 0.88) when adjusted for possible
      confounding factors. Sepsis rates did not differ between those with recent or
      prolonged preterm PROM at any gestational age. CONCLUSION: The presence of
      membrane rupture before delivery was not associated with increased neonatal
      mortality in any gestational age group. The effects of a prolonged latency period
      were not consistent across gestational ages.

PMID- 21099607
TI  - The role of embryonic origin in preeclampsia: a comparison of autologous in vitro
      fertilization and ovum donor pregnancies.
AB  - OBJECTIVE: To compare the risk of gestational hypertension and preeclampsia in
      pregnancies conceived through standard in vitro fertilization (IVF) using
      autologous oocytes with pregnancies conceived using donated oocytes. METHODS: We
      conducted a retrospective, matched cohort study of women undergoing IVF using
      autologous compared with donor oocytes between 1998 and 2005. Women with live
      births resulting from oocyte donor pregnancies were matched for age and plurality
      (singleton or twin) with women undergoing autologous IVF. Primary outcomes were
      the incidence of preeclampsia or gestational hypertension (with and without
      proteinuria) in the third trimester. Data on preterm delivery, low birth weight,
      and embryo cryopreservation were also recorded. RESULTS: Outcome data were
      available for 158 pregnancies, including 77 ovum-donor recipient pregnancies and
      81 pregnancies using autologous oocytes. There were no differences in age,
      parity, and gestational type between the two cohorts. The incidence of
      gestational hypertension and preeclampsia was significantly higher in ovum-donor
      recipients compared with women undergoing autologous IVF (24.7% compared with
      7.4%, P<.01, and 16.9% compared with 4.9%, P=.02, respectively). Ovum-donor
      recipients were more likely than women undergoing autologous IVF to deliver
      prematurely (34% compared with 19%). This association remained after controlling
      for multiple gestation (odds ratio 2.6, 95% confidence interval 1.04-6.3).
      Sixteen pregnancies from cryopreserved embryos were more likely to have
      hypertensive disorders of pregnancy (odds ratio 5.0, 95% confidence interval 1.2
      20.5). CONCLUSION: Pregnancies derived from donor oocytes and cryopreserved
      thawed embryos may be at a higher risk for hypertensive disorders of pregnancy.
      These findings inform future research and help counsel women using assisted
      reproductive technology.

PMID- 21099608
TI  - A simple checklist for preventing major complications associated with cesarean
      delivery.
AB  - I propose a simple, evidence-based, eight-item checklist that, if followed,
      should reduce the frequency of many of the most serious complications associated
      with cesarean delivery: endometritis, wound infection, wound disruption,
      thrombophlebitis, and uterine scar dehiscence in a subsequent pregnancy. The
      frequency of abdominal wound infections can be reduced significantly by using
      electric clippers, rather than a razor, to remove the hair at the site of the
      surgical incision, washing the skin with a chlorhexidine solution, and
      administering broad-spectrum antibiotic prophylaxis before the start of surgery
      rather than after the neonate's umbilical cord has been clamped. Administration
      of broad-spectrum antibiotic prophylaxis and removal of the placenta by traction
      on the umbilical cord, rather than by manual extraction, will reduce the
      frequency of postcesarean endometritis. Closure of the uterine incision in two
      layers rather than one will significantly reduce the frequency of scar dehiscence
      in a subsequent pregnancy. Closure of the deep subcutaneous layer in patients
      whose subcutaneous tissue is greater than 2 cm in thickness will significantly
      reduce the risk of seroma, hematoma, and subsequent wound disruption. Institution
      of appropriate prophylaxis for deep vein thrombosis in intermediate and high-risk
      patients will reduce the risk of subsequent thromboembolic events.

PMID- 21099609
TI  - Electronic fetal monitoring as a public health screening program: the arithmetic
      of failure.
AB  - Electronic fetal monitoring has failed as a public health screening program.
      Nevertheless, most of the four million low-risk women giving birth in the United
      States each year continue to undergo this screening. The failure of this program
      should have been anticipated and thus avoided had the accepted principles of
      screening been considered before its introduction. All screening tests have poor
      positive predictive value when searching for rare conditions such as fetal death
      in labor or cerebral palsy. This problem is aggravated when the screening test
      does not have good validity as is the case with electronic fetal monitoring.
      Because of low-prevalence target conditions and mediocre validity, the positive
      predictive value of electronic fetal monitoring for fetal death in labor or
      cerebral palsy is near zero. Stated alternatively, almost every positive test
      result is wrong. To avoid such costly errors in the future, the prerequisites for
      any screening program must be fulfilled before the program is begun.

PMID- 21099610
TI  - Where is the "M" in maternal-fetal medicine?
AB  - In contrast to the generally encouraging trend regarding global maternal
      mortality, there has been an apparent increase in the maternal mortality ratio in
      the United States. Although maternal death remains a relatively rare adverse
      event in this country, programs to reduce maternal mortality also will result in
      a reduction in maternal morbidity, which is a far more prevalent problem.
      Progress in the field of maternal-fetal medicine over the past several decades
      has been largely attributable to improvements in fetal and neonatal medicine. We
      need to develop an organized, national approach focused on reducing maternal
      mortality and morbidity. The goal will be to outline a specific plan for
      clinical, educational, and research initiatives to put the "M" back in maternal
      fetal medicine.

PMID- 21099611
TI  - Evaluating the safety and effectiveness of new drugs.
AB  - Prescribers seek to provide their patients with access to the latest innovations
      in medicine to maximize their health status. When a new drug comes to market, it
      often has not been as widely tested as other available therapies, and its
      effectiveness and safety cannot be fully evaluated. To address this problem,
      physicians can use the STEPS (Safety, Tolerability, Effectiveness, Price, and
      Simplicity) mnemonic to provide an analytic framework for making better decisions
      about a new drug's appropriate place in therapy. A key element is to base this
      evaluation on patient-oriented evidence rather than accept disease-oriented
      evidence (which may be misleading), while avoiding inappropriate reliance on
      studies that report only noninferiority results or relative-risk reductions. The
      primary question to ask for each new drug prescribing decision is, "Is there good
      evidence that this new drug is likely to make my patient live longer or better
      compared with the available alternatives?"

PMID- 21099612
TI  - Breast cancer screening in women at average risk and high risk.
AB  - Recent controversies over the recommendations for breast cancer screening have
      created some uncertainty about the best methods of providing this care for women,
      particularly women at average risk for breast cancer. This article reviews the
      current recommendations for breast cancer screening from various national
      organizations and the scientific data behind these recommendations, and it
      highlights some of the controversies and the reasons behind the differing
      viewpoints. This article focuses on providing the obstetrician-gynecologist with
      evidence-based recommendations for counseling and screening women who are at
      average and high risk for breast cancer. The ability to identify women at higher
      risk for breast cancer and the appropriate clinical use of mammography,
      ultrasonography, MRI, clinical breast examination, and self-breast examination
      ("breast self-awareness") for breast cancer screening in these different
      populations are discussed. Finally, incorporating specific recommendations for
      breast cancer screening in women at average and high risk into practice are
      included.

PMID- 21099613
TI  - Robotic-assisted hysterectomy for endometrial cancer compared with traditional
      laparoscopic and laparotomy approaches: a systematic review.
AB  - OBJECTIVE: To summarize comparative studies describing clinical outcomes of
      robotic-assisted surgeries compared with traditional laparoscopic or laparotomy
      techniques for the treatment of endometrial cancer. DATA SOURCES: Using search
      words "robotic hysterectomy" and "endometrial cancer," 22 citations were
      identified from Medline and PubMed (2005 to February 2010). METHODS OF STUDY
      SELECTION: We selected English language studies reporting at least 25 robotic
      cases compared with laparoscopic or laparotomy cases that also addressed surgical
      technique, complications, and perioperative outcomes. Patients underwent total
      hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. TABULATION,
      INTEGRATION, AND RESULTS: Eight eligible comparative studies were identified that
      included 1,591 patients (robotic=589, laparoscopic=396, and laparotomy=606).
      Pooled means of the resected aortic lymph nodes for robotic hysterectomy and
      laparoscopy were 10.3 and 7.8 (P=.15), and robotic hysterectomy and laparotomy
      were 9.4 and 5.7 (P=.28). Pooled means of pelvic lymph nodes for robotic and
      laparoscopic hysterectomy were 18.5 and 17.8 (P=.95) and 18.0 compared with 14.5
      (P=.11) for robotic hysterectomy compared with laparotomy. Estimated blood loss
      was reduced in robotic hysterectomy compared with laparotomy (P<.005) and
      laparoscopy (P=.001). Length of stay was shorter for both robotic and
      laparoscopic cases compared with laparotomy (P<.01). Operative time for robotic
      hysterectomy was similar to laparoscopic cases but was greater than laparotomy
      (P<.005). Conversion to laparotomy for laparoscopic hysterectomy was 9.9%
      compared with 4.9% for robotic cases (P=.06). Vascular, bowel, and bladder
      injuries; cuff dehiscence; and thromboembolic complications were similar for each
      surgical method. Transfusions for robotic hysterectomy compared with laparotomy
      was 1.7% and 7.2% (P=.06) and robotic hysterectomy compared were laparoscopy was
      2.6% and 5.0% (P=.22). CONCLUSION: Perioperative clinical outcomes for robotic
      and laparoscopic hysterectomy appear similar with the exception of less blood
      loss for robotic cases and longer operative times for robotic and laparoscopy
      cases.

PMID- 21099614
TI  - Association of anticardiolipin antibodies with preeclampsia: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To systematically review the evidence of the association of
      anticardiolipin antibodies with preeclampsia. DATA SOURCES: PubMed and LILACS
      were perused up to June 2009, citations were searched using the ISI Web of
      Knowledge database, textbooks and reference lists were reviewed, and experts were
      contacted. Search terms included "antiphospholipid syndrome," "Hughes' syndrome,"
      "anticardiolipin antibodies," "antiphospholipid antibodies," "anti-cardiolipin,"
      "preeclampsia," and "pre-eclampsia." METHODS OF STUDY SELECTION: Inclusion
      criteria were: cohorts, case-control, or controlled cross-sectional studies;
      healthy pregnancy as controls; no autoimmune diseases; immunoglobulin (Ig)G, IgM
      anticardiolipin antibody of at least 20 units by enzyme-linked immunosorbent
      assay, or both; and end-point preeclampsia. TABULATION, INTEGRATION, AND RESULTS:
      Our search generated 68,528 entries and 64 full-text articles were reviewed.
      Twelve studies were included in the meta-analysis. Pooled odds ratio (OR) for
      association of anticardiolipin antibodies with preeclampsia was 2.86 (95%
      confidence interval [CI], 1.37-5.98). Pooled OR for anticardiolipin antibodies
      and severe preeclampsia was 11.15 (95% CI 2.66-46.75). Funnel plot showed minor
      asymmetry, and the Egger test was not significant (P=.359). Meta-regression
      identified study design and size as related to heterogeneity. CONCLUSION:
      Moderate-to-high levels of anticardiolipin antibodies are associated with
      preeclampsia, but there is insufficient evidence to use anticardiolipin
      antibodies as predictors of preeclampsia in clinical practice.

PMID- 21099615
TI  - Understanding the spectrum of the female athlete triad.

PMID- 21099617
TI  - Emergency postpartum hysterectomy for uncontrolled postpartum bleeding: a
      systematic review.

PMID- 21099618
TI  - Generational issues in the ob-gyn workplace: "Marcus Welby, MD," versus "Scrubs".

PMID- 21099620
TI  - Chorioamnionitis and cerebral palsy: a meta-analysis.

PMID- 21099621
TI  - Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy
      menstrual bleeding: a randomized controlled trial.

PMID- 21099623
TI  - Vaginal mesh for prolapse: a randomized controlled trial.

PMID- 21099625
TI  - Vaginal mesh for prolapse: a randomized controlled trial.

PMID- 21099628
TI  - Ultrasonographic cervical length and risk of hemorrhage in pregnancies with
      placenta previa.

PMID- 21099631
TI  - Pelvic inflammatory disease.

PMID- 21099636
TI  - ACOG Practice Bulletin No. 117: Gynecologic care for women with human
      immunodeficiency virus.
AB  - The increased use of screening tests has led to the identification of large
      numbers of women with human immunodeficiency virus (HIV). Consequently, there is
      an increased role for obstetrician-gynecologists in caring for infected women.
      Women infected with HIV are living longer, healthier lives and, therefore, the
      need for routine gynecologic care has increased. The purpose of this document is
      to educate clinicians about routine HIV screening practices as well as basic
      women's health screening and care, family planning, and preconception care for
      women who are infected with HIV.

PMID- 21099637
TI  - The nurse consultant in YOU.

PMID- 21099638
TI  - NAON Foundation "putting feet on it".

PMID- 21099641
TI  - Scheuermann's thoracic kyphosis in the adolescent patient.
AB  - Scheuermann's thoracic kyphosis is a condition characterized by increased
      posterior rounding of the thoracic spine in association with structural deformity
      of the vertebral elements. It is a structural deformity of the spine that is
      classically characterized by anterior wedging of 5 degrees  or more of 3 adjacent
      thoracic vertebral bodies with kyphosis measuring greater than 45 degrees 
      between T5 and T12. The cause of the deformity remains unknown but it is believed
      to be multifactorial, and it likely has a genetic component as well. Most
      adolescent patients seek orthopaedic evaluation for increased rounding and
      deformity of the thoracic spine that is occasionally associated with back pain.
      Parental concerns are also often related to the cosmetic deformity and the
      progressive nature of the condition. Bracing has been demonstrated to be an
      effective nonsurgical treatment modality for the skeletally immature child and/or
      adolescent with a progressive deformity. Operative management has been advocated
      for adolescents with progressive kyphosis measuring over 70 degrees , for those
      who have had progression despite bracing, for patients with intractable back
      pain, and also for patients with unacceptable cosmetic deformity. Surgical
      options include posterior spinal arthrodesis with or without anterior spinal
      release via thoractomy or video-assisted thoracoscopic surgery (VATS). This
      article will review the diagnosis, pathophysiology, physical examination
      findings, and the nonoperative and surgical treatment options for adolescent
      patients with Scheuermann's kyphosis of the thoracic spine.

PMID- 21099643
TI  - Implementing a relationship-based care model on a large orthopaedic/neurosurgical
      hospital unit.
AB  - Implementing relationship-based care provides nurses with the opportunity to
      develop positive relationships with patients/families/staff and improve patient
      outcomes. This can be challenging on a large orthopaedic/neurosurgical hospital
      unit. The purpose of this article is to share the experiences from this process
      to encourage other units, with similar patient populations and size, to adopt
      relationship-based care as their care delivery model. Being able to give quality
      care in a safe and trusting environment is advantageous to the patient and
      satisfying to the nurse.

PMID- 21099645
TI  - New design of care: Assessment of an interdisciplinary orthopaedic clinic with a
      pivot nurse in the province of Quebec.
AB  - BACKGROUND: New designs of care in orthopaedic clinics are needed to cope with
      the shortage of orthopaedic surgeons and the lengthening of waiting times.
      OBJECTIVE: To assess the effectiveness of an interdisciplinary orthopaedic clinic
      with a pivot nurse in the Canadian province of Quebec with regard to
      accessibility, quality of care, efficacy and efficiency of the clinic, and
      patient's quality of life. METHODS: Two strategies were developed: (1) a selected
      cohort of new patients attending an orthopaedic service from February to
      September 2008 were entered into a database recording patient details, source of
      referral, diagnosis, satisfaction, and quality of life (36-Item Short Form Health
      Survey version 2). In this setting, 2 sets of questionnaires were administered to
      the patients: the first one during the first visit and the second one, 2 months
      later. A total of 243 patients from the case control were compared with 89
      patients of the case study, where an interdisciplinary orthopaedic clinic with a
      pivot nurse has been developed; (2) costs per patient were calculated using the
      staff timesheets provided by the two orthopaedic clinics. RESULTS: The results
      showed a significant reduction in the waiting-list duration (accessibility) in
      the case study clinic owing to a strong decrease in the inappropriate
      consultations with the orthopaedic consultant. The quality of care remained high,
      and the target surgeries for total hip and knee replacement were reached, despite
      a strong shortage of orthopaedic doctors. CONCLUSION: Interdisciplinary
      orthopaedic clinic with a pivot nurse is a new approach in the province of Quebec
      and first results are encouraging.

PMID- 21099646
TI  - Can you go the distance? Attending the virtual classroom.
AB  - Distance learning via the World Wide Web offers convenience and flexibility.
      Online education connects nurses geographically in a manner that the traditional
      face-to-face learning environment lacks. Delivered in both a synchronous (real
      time interaction) or asynchronous (delayed interaction) format, distance programs
      continue to provide nurses with choice, especially in the pursuit of advanced
      degrees. This article explores the pros and cons of distance education, in
      addition to the most popular platform used in distance learning today, the
      Blackboard Academic Suite. Characteristics of the potential enrollee to ensure a
      successful distance education experience are also discussed. Distance nursing
      programs are here to stay. Although rigorous, the ease of accessibility makes
      distance learning a viable alternative for busy nurses.

PMID- 21099647
TI  - Is guided imagery effective in reducing pain and anxiety in the postoperative
      total joint arthroplasty patient?
AB  - PURPOSE: To evaluate the effect of guided imagery as an intervention to reduce
      pain and anxiety in patients undergoing a total joint arthroplasty. SAMPLE: A
      total of 121 patients scheduled for elective total joint arthroplasty. METHODS:
      The design for this study was a 2-group quasi-experimental design. The
      intervention group listened to a guided imagery CD containing a message to
      develop a sense of relaxation and harmony. The intervention and control groups
      were compared on self-reported pain and anxiety levels postoperatively on Days 1,
      2, and 3. RESULTS: There was no significant difference in pain and anxiety levels
      between the groups. However, the intervention group had lower levels of anxiety
      and pain at all time points. Both groups followed a similar anxiety and pain
      pattern with the highest reported levels at Day 2. CONCLUSIONS: Conduct further
      research of guided imagery as an intervention for reducing pain and anxiety
      utilizing randomized controlled trials with a diverse sample of patients.

PMID- 21099648
TI  - Osteoarticular manifestations of Mycobacterium tuberculosis infection.
AB  - Mycobacterium tuberculosis has affected humans for much of our existence. The
      incidence of global tuberculosis infection continues to rise, especially in
      concert with HIV coinfection. Many disease processes, such as diabetes, increase
      the likelihood of tuberculosis infection. Tuberculosis bacteria can infect any
      bone, joint, tendon, or bursa; however, the most common musculoskeletal site for
      infection includes the spine and weight-bearing joints of the hip and knee. Many
      patients who present with osteoarticular tuberculosis infection will have a
      gradual onset of pain at the site of infection. Many patients who develop a
      musculoskeletal tuberculosis infection will have no evidence of a pulmonary
      tuberculosis infection on x-ray film and many will have very mild symptoms with
      the initial infection. Healthcare providers must remember that many patients who
      develop tuberculosis infection do not progress to active tuberculosis disease;
      however, the latent infection may become active with immune compromise.

PMID- 21099652
TI  - Acute hematogenous osteomyelitis in children: differences in clinical
      manifestations and management.

PMID- 21099653
TI  - Update on rotavirus trends and the importance of surveillance.

PMID- 21099654
TI  - Intensive care admissions for children with imported malaria in the United
      kingdom.
AB  - This study describes 977 children with imported malaria in England and Wales
      between 2004 and 2008, focusing on 29 (3.0%) patients admitted to intensive care,
      of whom 10 had cerebral malaria, 4 required inotropes, and 1 had concurrent
      septicemia. The remaining 14 were admitted for monitoring only. None died, but 1
      child developed cerebellar infarction.

PMID- 21099655
TI  - Fever and bleeding in a newborn baby.

PMID- 21099656
TI  - Delayed therapy for otitis media.

PMID- 21099657
TI  - Ureaplasma parvum meningitis in a full-term newborn.

PMID- 21099658
TI  - Fixed orthodontic appliance and infective endocarditis.

PMID- 21099660
TI  - Do infants and toddlers prefer nasal swabs or washes for specimen collection?

PMID- 21099662
TI  - Effect of the ACGME duty hours restrictions on surgical residents and faculty: a
      systematic review.
AB  - PURPOSE: Educators in surgical training programs are concerned that the
      Accreditation Council for Graduate Medical Education (ACGME) duty hours
      limitations may adversely affect surgical residents' education, especially their
      operative experience, so the authors aimed to evaluate the impact of duty hours
      reductions on surgical residency. METHOD: The authors searched English- and
      French-language literature (2000-2008) for articles about the impact of duty
      hours restrictions on surgical residents' education and well-being and on faculty
      educators. They used the following databases: MEDLINE, EMBASE, Cochrane Central
      Register of Controlled Trials, and ERIC. The authors included every report that
      examined the effects of duty hours limits on surgical training, excluding opinion
      papers and editorials. Two reviewers independently performed data extraction and
      quality assessment for all reports and resolved disagreements by consensus.
      RESULTS: The authors retrieved 1,146 reports and included 56 in the study. They
      compiled positive and negative outcomes on (1) residents' education, (2) resident
      lifestyle, and (3) surgical faculty. Overall, the effects of duty hours
      reductions on residents' education and lifestyle were positive or neutral, but
      the effects on surgical faculty were negative. The 16 articles with the highest
      quality scores had 27 positive themes and 11 negative themes. CONCLUSIONS: This
      is the largest and most current review of the literature addressing the effect of
      the ACGME duty hours limitations on surgical training. Limitations had a positive
      effect on residents but a negative effect on surgical faculty. Importantly, duty
      hours limitations did not adversely affect surgical residents' operating-room
      experience.

PMID- 21099663
TI  - Conceptual frameworks in the study of duty hours changes in graduate medical
      education: a review.
AB  - PURPOSE: Conceptual frameworks are approaches to a research problem that specify
      key entities and their relationships. The 2009 Institute of Medicine (IOM) report
      on resident duty hours, subsequent studies, and published responses to the report
      present a variety of conceptual frameworks for the study of the impact of duty
      hours regulations. The authors sought to identify and describe these conceptual
      frameworks and their implications. METHOD: The authors reviewed the IOM report
      and articles in both peer-reviewed and non-peer-reviewed literature for the
      period January 2008 through April 2010, identified using multiple electronic
      databases including PubMed, EMBASE, CINAHL, BEME, and PsycInfo. Studies that
      explicitly described or argued for the effect of resident duty hours on any other
      outcome, as judged by consensus of multiple reviewers, were included. The authors
      selected 239 of 858 studies reviewed. Several of the authors reviewed articles to
      identify conceptual frameworks used implicitly or explicitly to describe the
      relationship between duty hours (or duty hours regulations) and outcomes.
      Identification was by consensus. RESULTS: Twenty-three conceptual frameworks were
      identified. Several made contradictory predictions about the impact of duty hours
      regulations on patient outcomes, resident education, and other key outcomes.
      CONCLUSIONS: The concept of duty hours itself is contested, and little attention
      has been paid to the nature and intensity of the activities that occupy
      residents' hours. Much research focuses on isolated outcomes of duty hours
      changes without considering mediation or moderation. More studies are needed to
      define trade-offs between outcomes and the value society places on these trade
      offs.

PMID- 21099664
TI  - Protective interleukin-28B genotype affects hepatitis C virus clearance, but does
      not contribute to HIV-1 control in a cohort of African-American elite
      controllers/suppressors.
AB  - We tested the hypothesis that a single nucleotide polymorphism (SNP) located near
      the interleukin-28B gene is associated with the control of hepatitis C virus and
      HIV-1 replication in elite controllers/suppressors. We show here that the
      protective genotype is not overrepresented in elite controllers/suppressors
      compared with HIV-1-seronegative patients and HIV-1-infected patients with viral
      loads more than 10 000 copies/ml. Thus, it appears that this SNP is not
      associated with the elite control of HIV-1 infection.

PMID- 21099665
TI  - Interleukin-28B gene polymorphisms do not influence the susceptibility to HIV
      infection or CD4 cell decline.
AB  - The critical role of interleukin-28B (IL28B)/interferon-lambda3 (IFN-lambda3)
      polymorphisms on the susceptibility to hepatitis C virus infection and the
      response to peginterferon-ribavirin therapy has encouraged exploration of similar
      effects on other viruses. Given that IFN-lambda mediates anti-HIV-1 activity, the
      protective role of IL28B polymorphisms was examined in 29 seronegative
      individuals at risk for HIV-infection and in 68 HIV-positive carriers with and
      without rapid progression of immunodeficiency. No protective role of IL28B
      polymorphism was found examining both HIV-disease progression and HIV-protection.

PMID- 21099667
TI  - Genotypic tropism testing: evidence-based or leap of faith?

PMID- 21099666
TI  - A phase IV, double-blind, multicentre, randomized, placebo-controlled, pilot
      study to assess the feasibility of switching individuals receiving efavirenz with
      continuing central nervous system adverse events to etravirine.
AB  - BACKGROUND: Two nucleoside reverse transcriptase inhibitors (NRTIs) and efavirenz
      (EFV) is a recommended initial regimen for HIV-1. Most EFV-related central
      nervous system (CNS) toxicity resolves early though symptoms may persist; we
      studied switching to etravirine (ETR) in these individuals. METHODS: A
      randomized, double-blind trial in patients with viral suppression but ongoing CNS
      adverse events after more than 12 weeks EFV. Patients received 2NRTI/EFV/ETR
      placebo (delayed switch) or 2NRTI/ETR/EFV-placebo (immediate switch) for 12 weeks
      followed by 12-week open-label phase (2NRTI/ETR). Primary end-point was
      percentage with G2-4 CNS adverse events at 12 weeks. RESULTS: Thirty-eight men;
      20/18 were randomized to immediate switch/delayed switch; median CD4 was 444/498
      cells/MUl, respectively. Baseline CNS adverse events were similar. Nineteen
      immediate switch patients completed follow-up (one lost to follow-up) and 13 on
      delayed switch (two lost to follow-up, two withdrawn consent, one adverse event).
      Immediate switch G2-4 CNS adverse event: 90% at baseline, 60% at week 12 (P =
      0.041). Delayed switch G2-4 CNS adverse event: 88.9% at baseline, 81.3% at week
      12 (P = ns). Combined (both arms) percentage decline in G2-4 CNS adverse event
      after 12 weeks of ETR was significant for overall adverse events, insomnia,
      abnormal dreams and nervousness (P = 0.009, 0.016, 0.001, and 0.046,
      respectively). All participants on study maintained HIV-RNA below 50 and median
      week 24 CD4 was 593 and 607 cells/MUl on immediate switch and delayed switch. Two
      participants experienced new G3-4 adverse events [delayed switch: G3 flatulence
      on EFV); immediate switch: G4 viral URTI on ETR (SAE)]. CONCLUSION: Switching EFV
      to ETR led to a significant reduction in overall G2-4 CNS adverse events,
      including insomnia, abnormal dreams and nervousness as individual adverse event.
      Lack of improvement for some events suggests other causative factors.

PMID- 21099668
TI  - A prospective study of alcohol consumption and HIV acquisition among injection
      drug users.
AB  - OBJECTIVE: to estimate the effect of alcohol consumption on HIV acquisition while
      appropriately accounting for confounding by time-varying risk factors. DESIGN:
      african-American injection drug users in the AIDS Link to Intravenous Experience
      cohort study. Participants were recruited and followed with semiannual visits in
      Baltimore, Maryland between 1988 and 2008. METHODS: marginal structural models
      were used to estimate the effect of alcohol consumption on HIV acquisition.
      RESULTS: at entry, 28% of 1525 participants were women with a median (quartiles)
      age of 37 (32-42) years and 10 (10-12) years of formal education. During follow
      up, 155 participants acquired HIV and alcohol consumption was 24, 24, 26, 17, and
      9% for 0, 1-5, 6-20, 21-50, and 51-140 drinks per week over the prior 2 years,
      respectively. In analyses accounting for sociodemographic factors, drug use, and
      sexual activity, hazard ratios for participants reporting 1-5, 6-20, 21-50, and
      51-140 drinks per week in the prior 2 years compared to participants who reported
      0 drinks per week were 1.09 (0.60-1.98), 1.18 (0.66-2.09), 1.66 (0.94-2.93), and
      2.12 (1.15-3.90), respectively. A trend test indicated a dose-response
      relationship between alcohol consumption and HIV acquisition (P value for trend =
      9.7 * 10). CONCLUSION: a dose-response relationship between alcohol consumption
      and subsequent HIV acquisition is indicated, independent of measured known risk
      factors.

PMID- 21099669
TI  - Intraocular and plasma HIV-1 RNA loads and HIV uveitis.
AB  - OBJECTIVE: The objective of this study was to analyze human immunodeficiency
      virus (HIV) dynamics across the blood-retinal barrier and to determine whether
      the high levels of HIV in the eye are associated with any ocular disorders in HIV
      infected patients. DESIGN: This study included a prospective case series of 40
      HIV-positive patients with uveitis. INTERVENTION: Clinical and laboratory
      examinations included plasma and intraocular HIV-1 RNA loads as well as the
      clinical manifestations of uveitis. RESULTS: Intraocular HIV-1 RNA was detected
      in 32% (13/40) of HIV-positive patients with uveitis. Intraocular HIV-1 RNA loads
      were associated with high HIV-1 RNA plasma loads (P < 0.001) and not being on
      HAART therapy (P = 0.005). In addition, detectable intraocular HIV-1 RNA levels
      were higher in patients with the absence of retinal lesions (P = 0.008). In three
      patients, the HIV load in the eye largely exceeded that of plasma. These three
      patients had all bilateral anterior uveitis and/or vitritis without retinal
      lesions and exhibited no evidence of other intraocular infectious agents causing
      uveitis than HIV itself. CONCLUSION: The eye can form a sanctuary where HIV might
      replicate and cause an inflammatory reaction.

PMID- 21099670
TI  - TAP-independent human histocompatibility complex-Cw1 antigen processing of an HIV
      envelope protein conserved peptide.
AB  - Individuals with nonfunctional transporters associated with antigen processing
      (TAP) complexes are not particularly susceptible to viral infections or
      neoplasms. Therefore, their immune system must be reasonably efficient, and the
      present, though reduced, cytolytic CD8 alphabeta T subpopulation specific for TAP
      independent antigens may be sufficient to establish an immune defense protecting
      against viral infections in these individuals. The objective of the present study
      was to identify TAP-independent ligands from HIV gp160 protein. An analysis and
      comparison of complex human histocompatibility complex (HLA)-bound peptide pools
      isolated from large quantities of healthy or HIV gp160-expressing human cells was
      performed using mass spectrometry and bioinformatics tools. A conserved TAP
      independent HLA peptide ligand endogenously processed and presented in infected
      human cells was identified. This ligand originates from the envelope protein
      bound to the HLA-Cw1 class I molecule with high affinity. It was concluded that
      HLA class I peptides derived from a large fraction of the N-terminal HIV envelope
      protein could be presented even in the absence of the TAP complex.

PMID- 21099671
TI  - Millennium development goal 6 and HIV infection in Zambia: what can we learn from
      successive household surveys?
AB  - BACKGROUND: Geographic location represents an ecological measure of HIV status
      and is a strong predictor of HIV prevalence. Given the complex nature of location
      effects, there is limited understanding of their impact on policies to reduce HIV
      prevalence. METHODS: Participants were 3949 and 10 874 respondents from two
      consecutive Zambia Demographic and Health Surveys from 2001/2007 (mean age for
      men and women: 30.3 and 27.7 years, HIV prevalence 14.3% in 2001/2002; 30.3 and
      28.0 years, HIV prevalence of 14.7% in 2007). A Bayesian geo-additive mixed model
      based on Markov Chain Monte Carlo techniques was used to map the change in the
      spatial distribution of HIV/AIDS prevalence at the provincial level during the 6
      year period, accounting for important risk factors. RESULTS: Overall HIV/AIDS
      prevalence changed little over the 6-year period, but the mapping of residual
      spatial effects at the provincial level suggested different regional patterns. A
      pronounced change in odds ratios in Lusaka and Copperbelt provinces in 2001/2002
      and in Lusaka and Central provinces in 2007 was observed following adjustment for
      spatial autocorrelation. Western province went from a lower prevalence area in
      2001 (13.4%) to a higher prevalence area in 2007 (17.3%). Southern province went
      from the highest prevalence area in 2001 (17.3%) to a lower prevalence area in
      2007 (15.9%). CONCLUSION: Findings from two consecutive surveys corroborate the
      Zambian government's effort to achieve Millennium Developing Goal (MDG) 6. The
      novel finding of increased prevalence in Western province warrants further
      investigation. Spatially adjusted provincial-level HIV/AIDS prevalence maps are a
      useful tool for informing policies to achieve MDG 6 in Zambia.

PMID- 21099672
TI  - Male circumcision and risk of HIV acquisition among MSM.
AB  - OBJECTIVES: To assess the association between male circumcision, insertive anal
      sex practices, and HIV acquisition in a cohort of MSM. METHODS: Data were from
      1824 HSV-2-seropositive, HIV-seronegative MSM, 1362 (75%) from Peru and 462 (25%)
      from the US, who participated in a randomized placebo-controlled trial of HSV-2
      suppression for HIV prevention (HPTN 039). Circumcision status was determined by
      examination at enrollment. HIV testing was done every 3 months for up to 18
      months. Partner-specific sexual behavior for up to the last three partners during
      the previous 3 months was analyzed. RESULTS: There was no significant association
      between male circumcision and HIV acquisition in univariate analysis [relative
      risk (RR) = 0.84, 95% confidence interval (CI) 0.50-1.42]. In a prespecified
      multivariate analysis that assumed a linear relationship between the proportion
      of insertive acts and effect of circumcision on HIV acquisition, the interaction
      between circumcision and proportion of insertive acts was not significant (P =
      0.11). In an exploratory analysis that categorized behavior with recent partners
      by proportion of insertive acts (<60 or >=60% insertive acts), circumcision was
      associated with a nonstatistically significant 69% reduction in the risk of HIV
      acquisition (RR = 0.31, 95% CI 0.06-1.51) among men who reported at least 60% of
      insertive acts with recent male partners. CONCLUSION: Circumcision does not have
      a significant protective effect against HIV acquisition among MSM from Peru and
      US, although there may be reduced risk for men who are primarily insertive with
      their male partners. This association needs to be investigated across diverse
      cohorts of MSM.

PMID- 21099673
TI  - HIV-1 trans-activator protein dysregulates IFN-gamma signaling and contributes to
      the suppression of autophagy induction.
AB  - OBJECTIVE AND DESIGN: HIV-1 transactivator protein, Tat, has been identified as
      an activator of HIV-1 replication. It also dysregulates cytokine production and
      apoptosis in T-cells. Of the various cell death processes, autophagy is a self
      digestion and degradation mechanism that recycles the contents of the cytosol,
      including macromolecules and cellular organelles, resulting in self-repair and
      conservation for survival. Recent reports demonstrated that autophagosomes can be
      activated by interferon-gamma (IFN-gamma) to participate in immune defence by
      processing foreign antigens for the recognition and killing of intracellular
      pathogens. As we previously showed that HIV-1 Tat perturbs IFN-gamma signaling
      through the suppression of STAT1 phosphorylation and consequently inhibits major
      histocompatibility complex class-II antigen expression, we postulate that Tat
      plays a role in regulating autophagy. METHODS: The role of STAT1 in IFN-gamma
      induced autophagy in primary human blood macrophages was examined using a small
      molecule inhibitor or siRNA specific for STAT1. The effect of HIV-1 Tat on
      autophagy was investigated by pretreating the macrophages with HIV-1 Tat and
      followed by IFN-gamma stimulation. The expressions of autophagy-associated genes
      and their effects on engulfing mycobacteria were examined. RESULTS: The
      activation of STAT1 resulted in IFN-gamma-induced LC3B protein expression and
      autophagosome formation. As postulated, HIV-1 Tat protein suppressed IFN-gamma
      induced autophagy processes, including LC3B expression. Additionally, HIV-1 Tat
      restricted the capturing of mycobacteria by autophagosomes. CONCLUSION: HIV-1 Tat
      suppressed the induction of autophagy-associated genes and inhibited the
      formation of autophagosomes. Perturbation of such cellular processes by HIV-1
      would impair the effective containment of invading pathogens, thereby providing a
      favorable environment for opportunistic microbes in HIV-infected individuals.

PMID- 21099674
TI  - Evaluation of ICU nurses' use of the clinical information system in Taiwan.
AB  - With the fast development of computer software and hardware, technology
      application is ubiquitous, and many healthcare services have integrated a
      clinical information system into daily practice. With today's information
      technology, everyone should possess basic computer competency to meet on-the-job
      demands and especially to use an information system in healthcare. Thus, the
      purpose of this study was to explore Taiwanese nurses' computer competency, the
      interface usability, and any change in the nurses' practice pattern as a result
      of the technology use. The current study adopted a descriptive research design,
      recruiting 114 nurses in medical and surgical ICUs to survey their technology
      use. Additionally, a total of 6780 observation values were obtained by a work
      sampling method to investigate the applicability of the information system. The
      results indicated that nurses with a higher education can use more computer
      applications and had better computer competency than other nurses. Additionally,
      computer competency was related to interface usability, and interface usability
      in the surgical ICU was rated higher than those in the medical ICU. Finally, the
      nursing practice patterns observed were related to the technology use. The
      results could serve as a reference for information technology usage evaluation in
      nursing.

PMID- 21099675
TI  - The effects of web-based diabetes education on diabetes care results: a
      randomized control study.
AB  - This study aimed to test the effects of providing Web-based diabetes education to
      individuals with type 2 diabetes on the A1c level and health check attendance.
      The study participants comprised 122 individuals with type 2 diabetes, who had
      access to the Internet, had completed their basic diabetes education, and had
      similar basic situational factors. Using a randomization method, these
      participants were chosen from the patients being monitored by the diabetes
      nurses. The experimental group (n = 61) was monitored via the Web. From
      measurements recorded in the sixth month of monitoring, we found that A1c levels
      of the individuals with diabetes who were monitored through the Web decreased (t
      = 6.63; P < .05), and the rate of attending health check visits increased (z =
      5.97; P< .05), while no difference was detected in the control group (t = -0.63;
      P = .534; z = -0.80; P = .426). To maintain glycemic control, Web use could be
      adopted as a complementary tool for monitoring individuals with diabetes.

PMID- 21099676
TI  - Exploring the relationship between patient call-light use rate and nurse call
      light response time in acute care settings.
AB  - Patient call-light usage and nurse responsiveness to call lights are two
      intertwined concepts that could affect patients' safety during hospital stays.
      Little is known about the relationship between call-light usage and call-light
      response time. Consequently, this exploratory study examined the relationship
      between the patient-initiated call-light use rate and the nursing staff's average
      call-light response time in a Michigan community hospital. It used hospital
      archived data retrieved from the call-light tracking system for the period from
      February 2007 through June 2008. Curve estimation regression and multiple
      regression analyses were conducted. The results showed that the call-light
      response time was not affected by the total nursing hours or RN hours. The nurse
      call-light response time was longer when the patient call-light use rate was
      higher and the average length of stay was shorter. It is likely that a shorter
      length of stay contributes to the nursing care activity level on the unit because
      it is associated with a higher frequency of patient admissions/discharges and
      treatment per patient-day. This suggests that the nursing care activity level on
      the unit and number of call-light alarms could affect nurse call-light response
      time, independently of the number of nurses available to respond.

PMID- 21099677
TI  - Scanning for safety: an integrated approach to improved bar-code medication
      administration.
AB  - This is a review of lessons learned in the postimplementation evaluation of a bar
      code medication administration technology implemented at a major tertiary-care
      hospital in 2001. In 2006, with a bar-code medication administration scan
      compliance rate of 82%, a near-miss sentinel event prompted review of this
      technology as part of an institutional recommitment to a "culture of safety."
      Multifaceted problems with bar-code medication administration created an
      environment of circumventing safeguards as demonstrated by an increase in manual
      overrides to ensure timely medication administration. A multiprofessional team
      composed of nursing, pharmacy, human resources, quality, and technical services
      formalized. Each step in the bar-code medication administration process was
      reviewed. Technology, process, and educational solutions were identified and
      implemented systematically. Overall compliance with bar-code medication
      administration rose from 82% to 97%, which resulted in a calculated cost
      avoidance of more than $2.8 million during this time frame of the project.

PMID- 21099678
TI  - The role of obesity and sleep apnea in atrial fibrillation.
AB  - PURPOSE OF REVIEW: To discuss the relationship between obesity and obstructive
      sleep apnea as they relate to the growing atrial fibrillation epidemic, and to
      discuss possible mechanistic links and implications for treatment of atrial
      fibrillation. RECENT FINDINGS: Increasing BMI plays an important role in
      development of atrial fibrillation in both men and women. Sleep-disordered
      breathing contributes to cardiac chamber enlargement, which may be responsible
      for increasing atrial fibrillation in this population. Patients with obstructive
      sleep apnea and/or obesity have less freedom from atrial fibrillation recurrence
      after catheter ablation for atrial fibrillation. SUMMARY: BMI is a strong
      predictor of future development of atrial fibrillation and should be considered
      as a risk factor for atrial fibrillation. Patients with obstructive sleep apnea
      and/or obesity have high atrial fibrillation recurrence rates following atrial
      fibrillation ablation.

PMID- 21099679
TI  - Catheter ablation of atrial fibrillation in the elderly.
AB  - PURPOSE OF REVIEW: Atrial fibrillation is increasingly prevalent among older
      adults and is a major contributor to morbidity in this population due to
      associated strokes, heart failure, and quality of life impairment. Catheter
      ablation for atrial fibrillation is demonstrated to be superior to antiarrhythmic
      therapy for the control of symptomatic and medically refractory atrial
      fibrillation, but its safety and efficacy in the elderly are not well understood.
      Clinical trials to guide the optimal management strategy in this population are
      lacking. RECENT FINDINGS: Several nonrandomized clinical studies have recently
      addressed the issue of catheter ablation in the elderly and show favorable rates
      of success. Unfortunately, these studies are limited by the relatively small
      numbers of patients examined and often by their single-center and retrospective
      nature. SUMMARY: Before the results of these studies can be extrapolated, data
      from larger cohorts of elderly patients followed prospectively are desperately
      needed.

PMID- 21099680
TI  - Vagal stimulation for heart failure.
AB  - PURPOSE OF REVIEW: On the very solid background of experimental and clinical
      studies pointing to the cardiovascular risks associated with depressed vagal
      reflexes and supported by specific experiments in animal models of heart failure,
      we are witnessing a rapidly growing interest in the very untraditional approach
      to the management of heart failure represented by chronic vagal stimulation.
      RECENT FINDINGS: Additional studies have been performed using vagal stimulation
      in animal models of heart failure showing that benefit can occur even in the
      absence of heart rate changes. The first in-man studies of chronic vagal
      stimulation have been performed, first as a single center and then as a small
      multicenter study with favorable results in terms of feasibility, safety, and
      efficacy. SUMMARY: The initial observations with chronic vagal stimulation in
      man, though limited by very small numbers, are very encouraging and seem to open
      new paths, or perhaps avenues, for the management of symptomatic heart failure.
      This transition between experimental and clinical approaches represents an
      exciting example of translational research.

PMID- 21099681
TI  - The techniques for catheter ablation of paroxysmal and persistent atrial
      fibrillation: a systematic review.
AB  - PURPOSE OF REVIEW: Ablation for atrial fibrillation has become a widely accepted
      and practiced treatment for this arrhythmia. However, the technique for ablation
      has evolved over time, particularly for the two distinct groups of paroxysmal and
      persistent atrial fibrillation. This review outlines the optimal techniques for
      ablation of these different subgroups of atrial fibrillation. RECENT FINDINGS:
      The most commonly applied techniques for atrial fibrillation ablation include
      isolation of the pulmonary venous antra, left-atrial linear ablation, and
      ablation of complex fractionated electrograms (CFEs) during atrial fibrillation.
      For patients with paroxysmal atrial fibrillation, isolation of the pulmonary
      venous antra appears to be sufficient, with effective and reproducible outcomes
      being reported across many centers. For persistent atrial fibrillation, the
      outcome of catheter ablation is less efficacious. It is widely believed that
      additional ablation targeting the substrate of atrial fibrillation maintenance is
      required beyond pulmonary venous isolation. Linear and CFE ablation have been the
      most commonly employed adjuvant strategies employed, but neither has been
      adequately compared with the other to make definitive recommendations. SUMMARY:
      Pulmonary venous antral isolation is the cornerstone of ablation of both
      paroxysmal and persistent atrial fibrillation. However, to obtain better outcomes
      in persistent atrial fibrillation, further adjuvant ablation, in the form of
      either linear or CFE ablation, will likely have to be performed to achieve
      comparable success rates.

PMID- 21099682
TI  - Genetic predisposition to sudden cardiac death.
AB  - PURPOSE OF REVIEW: Sudden cardiac death (SCD) is a major public health burden,
      and evidence from family history and from molecular studies on inherited
      arrhythmogenic syndromes indicates that genetic factors are important
      contributors to the risk of SCD. This review discusses recent advances on the
      genetic predisposition to SCD, with a specific focus on primary ventricular
      fibrillation and channelopathies. RECENT FINDINGS: Coronary artery disease is the
      major determinant of SCD, and its predisposing genetic background is complex.
      Very recently, a first genome-wide association study on primary ventricular
      fibrillation was published but the results are not conclusive and further studies
      with greater numbers are needed. Among channelopathies, long QT syndrome and
      Brugada syndrome are those in which more significant advances have been reported
      in the last year. Of note is the recently described early repolarization syndrome
      and the proposed classification of J wave syndromes. Revision of current
      guidelines for autopsy investigation has introduced molecular autopsy as a
      standard requirement for adequate assessment of SCD. SUMMARY: Interesting data on
      the genetic basis of sudden cardiac death have been published in the past year,
      and, whereas in the field of channelopathies research findings have been
      partially recognized by current guidelines and translated into clinical practice,
      in the field of coronary artery disease further advances are still needed.

PMID- 21099683
TI  - Prevention of atrial-esophageal fistula after catheter ablation of atrial
      fibrillation.
AB  - PURPOSE OF REVIEW: The formation of atrial-esophageal fistula after catheter
      ablation for atrial fibrillation is a rare but devastating complication with high
      mortality. Prevention is of utmost importance. We review the usefulness of
      currently available preventive measures. RECENT FINDINGS: Recent studies using
      endoscopy after atrial fibrillation ablation show the development of esophageal
      ulcerations in 14-17% of the patients. Risk factors for the occurrence of
      esophageal ulcerations seem to be a high esophageal luminal temperature during
      ablation, increased power during energy application at the posterior left-atrial
      wall, a short left atrium-to-esophagus distance, the use of nasogastric tubes and
      general anesthesia. The main available tools for prevention of atrial-esophageal
      fistula include: 1) Assessment of the esophagus position in the preprocedural
      CT/MRI scan. Its usefulness is limited by the potential of the esophagus to move.
      2) Tagging of the esophagus and real-time visualization of its course during the
      procedure. This can be achieved by introduction of a catheter into the esophagus
      and visualization in the three-dimensional electroanatomical system, by
      intracardiac ultrasound or by fluoroscopy. 3) Continuous monitoring of the
      esophageal luminal temperature during ablation with special temperature sensors.
      4) Reduction of power during energy application at the posterior left-atrial wall
      in close proximity to the esophagus. Despite application of preventive measures,
      cases of atrial-esophageal fistulas have been reported. SUMMARY: Several measures
      for prevention of atrial-esophageal fistula formation are available nowadays.
      Although these measures cannot completely eliminate the risk of fistula, it
      appears prudent to apply a combination of them during atrial fibrillation
      ablation.

PMID- 21099684
TI  - Prorenin and the (pro)renin receptor: recent advances and implications for
      retinal development and disease.
AB  - PURPOSE OF REVIEW: The renin-angiotensin system (RAS) is a treatment target for
      diabetic retinopathy and possibly other ocular diseases. However, angiotensin II
      blockade, though beneficial in diabetic retinopathy, is not completely
      retinoprotective. There is speculation that this shortfall is due to incomplete
      suppression of other RAS components. This review discusses the possibility that
      prorenin, which initiates the RAS, and the (pro)renin receptor [(P)RR] are
      potential candidates. RECENT FINDINGS: Despite prorenin being elevated in
      diabetic retinopathy, it remains unclear whether it exerts any functional effects
      in tissues, including the eye. Of interest are newly identified functions for the
      (P)RR based on its homology with an accessory protein of vacuolar ATPase,
      ATP6AP2. These include roles in the viability of the central nervous system,
      including the retina, via the Wnt signaling pathway. Additionally, (P)RR/ATP6AP2
      is implicated in other vacuolar ATPase-related events, including the regulation
      of cellular pH in the kidney and cell survival. Yet to be determined is whether
      the effects of (P)RR/ATP6AP2 are relevant to retinal cell function in health and
      disease and require the participation of its ligand prorenin. SUMMARY: New
      functions for the (P)RR highlight previously unrecognized roles for this receptor
      in cellular events that may have implications for both the developing and
      diseased retina.

PMID- 21099685
TI  - Role of renalase in the regulation of blood pressure and the renal dopamine
      system.
AB  - PURPOSE OF REVIEW: Renalase is a secreted amine oxidase that is synthesized in
      the kidney, and that metabolizes circulating catecholamines. Tissue and plasma
      renalase levels are decreased in models of chronic kidney disease. Recent data
      indicate that renalase deficiency is associated with increased blood pressure and
      elevated circulating catecholamines. The mechanisms of hypertension in renalase
      deficiency and the possibility that renalase regulates the renal dopamine system
      are discussed. RECENT FINDINGS: Characterization of the renalase knockout mouse
      model revealed that renalase deficiency increases SBP and DBP. Renal and cardiac
      functions are unaffected, but there is evidence of sympathetic activation, with
      elevation of plasma and urine catecholamines. Renalase is continually excreted in
      urine, and is enzymatically active and could modulate catecholamines levels in
      tubular fluid. Renalase expression is modulated by salt intake, and recombinant
      renalase has a potent and prolonged hypotensive effect on blood pressure in Dahl
      salt-sensitive rats and rats with chronic kidney disease. Plasma renalase levels
      are inversely associated with SBP in patients with resistant hypertension. A
      functional mutation in renalase (Glu37Asp) associated with essential hypertension
      also predicts more severe cardiac hypertrophy, dysfunction, and ischemia in
      individuals with stable coronary artery disease, comparable blood pressure and
      normal renal function. SUMMARY: Urinary renalase metabolizes urinary
      catecholamines, and perhaps regulates dopamine concentration in luminal fluid,
      and modulate proximal tubular sodium transport. Renalase deficiency is associated
      with increased sympathetic tone and resistant hypertension. Recombinant renalase
      is a potent antihypertensive agent in Dahl salt-sensitive rats and in rats with
      chronic kidney disease.

PMID- 21099686
TI  - Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin
      system in cardiovascular and renal disease.
AB  - PURPOSE OF REVIEW: Angiotensin-converting enzyme 2 (ACE2) has recently emerged as
      a key regulator of the renin-angiotensin system in both health and disease.
      RECENT FINDINGS: ACE2 deficiency is associated with elevated tissue and
      circulating levels of angiotensin II and reduced levels of angiotensin 1-7.
      Phenotypically, this results in a modest elevation in systolic blood pressure and
      left ventricular hypertrophy. In atherosclerosis-prone apolipoprotein E knockout
      mice, ACE2 deficiency results in augmented vascular inflammation and an
      inflammatory response that contributes to increased atherosclerotic plaque
      formation. In the kidney, ACE2 deficiency is associated with progressive
      glomerulosclerosis. Interventions such as ACE2 replenishment or augmentation of
      its actions have proven successful in reducing hypertension, plaque accumulation,
      and renal and cardiac damage in a range of different models. Although promising,
      the balance of the renin-angiotensin system remains complicated, with some
      evidence that overexpression of ACE2 may have adverse cardiac effects, and ACE2
      and its metabolic products may promote epithelial-to-mesenchymal transition.
      SUMMARY: Repletion of ACE2's activities offers a new strategy to complement
      current clinical interventions in treating hypertension, renal and cardiovascular
      disease. In particular conditions where ACE inhibition and angiotensin receptor
      blockade are partially effective, the adjunctive actions of ACE2 may not only
      reduce clinical escape but also augment the efficacy of interventions.

PMID- 21099687
TI  - Glomerular number and size variability and risk for kidney disease.
AB  - PURPOSE OF REVIEW: This review discusses current understandings of variability in
      glomerular number and size, and the implications for renal health. RECENT
      FINDINGS: The quantitative microanatomy of the normal human kidney varies widely.
      Of greatest significance, total nephron number varies at least 13-fold, and
      several genes and environmental factors that regulate human nephron endowment
      have been identified. Full or partial deletion of more than 25 genes in mice has
      been shown to result in renal hypoplasia and, when measured, reduced nephron
      endowment. Many more will likely be identified. As would be expected, some gene
      abnormalities increase nephron endowment above that found in control mice.
      Glomerular volume also varies widely, both between and within kidneys, and
      increased heterogeneity of glomerular volume within kidneys is associated with
      risk factors for kidney disease, including birth weight, age, race, body size and
      hypertension. SUMMARY: Data from several human populations indicate that the
      quantitative microanatomy of the human kidney varies considerably: total
      glomerular number varies at least 13-fold, mean glomerular volume varies up to
      seven-fold and the volumes of individual glomeruli within single kidneys can vary
      as much as eight-fold. Human glomerular number, size and size distribution are
      being found to correlate with risk factors for kidney disease. The genetic and
      fetal environmental regulators of nephrogenesis, and thereby nephron endowment,
      are being rapidly identified and will provide the bases for future clinical
      interventions. In contrast, the molecular regulation of glomerular size remains
      unclear.

PMID- 21099688
TI  - Neuroanatomic basis for traction-free preservation of the neural hammock during
      athermal robotic radical prostatectomy.
AB  - PURPOSE OF REVIEW: Much of the progress achieved in the past two decades in
      improving potency outcomes after radical prostatectomy has resulted from an
      improved appreciation of the anatomic basis of the nerves responsible for
      erection. We review the current literature evaluating the neuroanatomy of
      prostate and operative strategies for better preservation of sexual function.
      RECENT FINDINGS: Recent studies suggest an alternative and more complex course of
      nerves than previously described. Periprostatic nerves can be divided into three
      broad surgically identifiable zones: the proximal neurovascular plate, the
      predominant neurovascular bundle, and the accessory neural pathways. Better
      appreciation of the variable and often invisible anatomical course of the
      cavernosal nerves continues to engender innovations in surgical technique to
      optimize their preservation. SUMMARY: Improved anatomic understanding has
      optimized surgical technique in order to improve potency outcomes following
      radical prostatectomy.

PMID- 21099689
TI  - An update on holmium laser enucleation of the prostate and why it has stood the
      test of time.
AB  - PURPOSE OF REVIEW: Holmium laser enucleation of the prostate is an endoscopic
      alternative for the treatment of symptomatic benign prostatic hyperplasia for men
      with prostates of any size. Holmium laser enucleation of the prostate is superior
      to other modalities for the treatment of benign prostatic hyperplasia. We present
      the most current literature on this procedure. RECENT FINDINGS: In the 18-month
      span of this review, there have been a number of articles published on holmium
      laser enucleation of the prostate. These studies assessed the safety, efficacy,
      and durability of this procedure. Among these is the largest study to date
      providing supporting evidence to the long-term efficacy and safety of holmium
      laser enucleation of the prostate. Other studies provide compelling evidence to
      suggest that holmium laser enucleation of the prostate can be used in prostates
      of any size and can provide long-term durable outcomes. SUMMARY: Holmium laser
      enucleation of the prostate represents an effective, well tolerated, and durable
      procedure to relieve bladder outlet obstruction due to benign prostatic
      hyperplasia. Holmium laser enucleation of the prostate is a minimally invasive
      approach which accomplishes complete adenoma removal and, as such, provides
      unique advantages over other surgical treatments for men with benign prostatic
      hyperplasia.

PMID- 21099690
TI  - Transurethral resection of the prostate revisited and updated.
AB  - PURPOSE OF REVIEW: Electrosurgical transurethral resection (TUR) of the prostate
      (TURP) has dominated symptomatic benign prostatic hyperplasia (s-BPH) surgical
      treatment for almost a century. We analysed recent TURP publications, with
      emphasis on durability, morbidity, new technology advantages, future generation
      training and malignant disease. RECENT FINDINGS: TURP has declined due to medical
      therapy, but transcends other surgical challengers by proven outcomes durability
      over a decade. Adopting the modified-Clavien system may aid future morbidity
      comparisons. Properly used bipolar technology reduces major bleeding and
      seemingly abolishes TUR syndrome, but requires further study in anticoagulated
      patients. Residents are disturbingly short of TURP exposure, consequently
      experiencing more complications. Solutions include switching to ablative laser
      prostatectomy (which may carry higher long-term retreatment rates), adoption of
      bipolar technology, or simulator development and implementation. Concurrently
      performed transurethral resection of bladder tumor-TURP seems oncologically
      acceptable (in selected cases); incidentally detected significant prostate cancer
      at TURP may have declined, whereas TURP for prostate cancer may indicate the need
      for earlier androgen deprivation. SUMMARY: TURP is still rightly the dominant,
      most widely performed, versatile and cost-effective surgical treatment for s-BPH,
      reducing morbidity further with technical and technological developments. A
      better evidence base is required for newer technologies through large well
      designed multicentre-multinational randomized controlled trials incorporating
      standardized morbidity and long-term outcomes reporting.

PMID- 21099691
TI  - Botulinum neurotoxin A for male lower urinary tract symptoms.
AB  - PURPOSE OF REVIEW: Lower urinary tract symptoms (LUTS) related to benign
      prostatic hyperplasia (BPH) affects a large number of male patients from 45 years
      onward, increasing with age. Routine medical treatment is mainly limited to plant
      extracts, alpha-blockers, and 5-alpha-reductase inhibitors. Although all types of
      drug have a proven efficacy, they often do not sufficiently treat all aspects of
      LUTS related to BPH. Thus, there is a need for alternatives. Intraprostatic
      injections with botulinum neurotoxin type A (BoNT/A) seem to be a promising
      alternative. The purpose of this review is to summarize the most recent findings
      from basic science and clinical studies in relation to BoNT/A application in BPH
      related LUTS, thereby providing insight into the putative mechanism of action,
      the rationale for the use of BoNT/A in BPH-related LUTS, and the clinical
      outcomes. RECENT FINDINGS: There is some evidence that BoNT/A intraprostatic
      injections affect both, the static and dynamic component of BPH-related LUTS by
      reducing the prostate volume and by downregulation of alpha-1A-adrenoreceptors.
      Clinical trials demonstrated an easy and minimally invasive intraprostatic
      application of BoNT/A with a favourable safety profile. Efficacy seems to be good
      with significant improvements for several months in symptoms, urinary flow rate
      and reduction in postvoid residual, prostate volume, and also prostate-specific
      antigen in some studies. SUMMARY: BoNT/A seems to be a promising alternative in
      the treatment of BPH-related LUTS with a good tolerance and safety profile.
      However, the level of evidence is still low and further randomized controlled
      studies are mandatory.

PMID- 21099692
TI  - The impact of maternal highly active antiretroviral therapy and short-course
      combination antiretrovirals for prevention of mother-to-child transmission on
      early infant infection rates at the Mulago national referral hospital in Kampala,
      Uganda, January 2007 to May 2009.
AB  - BACKGROUND: Early HIV infant diagnosis and treatment have been shown to
      dramatically improve survival in infants. Despite these findings, infants
      accessing HIV diagnosis and treatment remain low in Uganda. We describe the
      antiretroviral (ARV) drugs given in the Mulago Hospital prevention of mother-to
      child transmission (PMTCT) program from January 2007 to May 2009 and its impact
      on early infant HIV infection rates. METHODS: Pregnant women identified as HIV
      infected in the Mulago antenatal clinics received one of the following regimens:
      short-course ARV prophylaxis plus single-dose nevirapine (sdNVP) in labor, highly
      active antiretroviral therapy (HAART), or sdNVP if they presented in labor.
      Infants received sdNVP and zidovudine (ZDV) for 1 week. Infants HIV diagnosis was
      done from 6 weeks after delivery. RESULTS: 62.3% of HIV-infected women received
      combination ARVs, including HAART. Early infection rates were highest among
      infants with no maternal ARV [36.4; 95% confidence interval (CI): 17.2 to 59.3]
      or only sdNVP (11.2; 95% CI: 8.1 to 14.8). Similar rates were observed for the
      group that took short-course ARVs, ZDV/sdNVP (4.6; 95% CI: 3.2 to 6.4), and
      ZDV/lamivudine/sdNVP (4.9; 95% CI: 3.1 to 7.2) and lowest rates for those that
      took HAART (1.7: 95% CI: 0.8 to 2.8). Overall infection rate was 5.0% (95% CI:
      4.1 to 5.9). CONCLUSIONS: Findings indicate low rates of infant infection for
      mothers receiving combination ARVs. These findings demonstrate that provision of
      combination ARV for PMTCT is feasible and effective in busy referral hospital's
      PMTCT programs in resource-limited settings.

PMID- 21099693
TI  - Early virologic failure and the development of antiretroviral drug resistance
      mutations in HIV-infected Ugandan children.
AB  - BACKGROUND: Without virologic testing, HIV-infected African children starting
      antiretroviral (ARV) therapy are at risk for undetected virologic failure and the
      development of ARV resistance. We sought to determine the prevalence of early
      virologic failure (EVF), to characterize the evolution of ARV-resistance
      mutations and to predict the impact on second-line therapy. METHODS: The
      prevalence of EVF (HIV RNA >400 copies/mL on sequential visits after 6 months of
      therapy) was identified among 120 HIV-infected Ugandan children starting ARV
      therapy. ARV mutations were identified by population sequencing of HIV-1 pol in
      sequential archived specimens. Composite discrete genotypic susceptibility scores
      were determined for second-line ARV regimens. RESULTS: EVF occurred in 16
      children (13%) and persisted throughout a median (interquartile ratio) 938 (760
      1066) days of follow-up. M184V and nonnucleoside reverse transcriptase inhibitor
      associated mutations emerged within 6 months of EVF; thymidine-analog-mutations
      arose after 12 months. Worse discrete genotypic susceptibility scores correlated
      with increasing duration of failure (Spearman R = -0.47; P = 0.001). Only 1 child
      met World Health Organization CD4 criteria for ARV failure at the time of EVF or
      during the follow-up period. CONCLUSIONS: A significant portion of HIV-infected
      African children experience EVF that would be undetected using CD4/clinical
      monitoring and resulted in the accumulation of ARV mutations that could
      compromise second-line therapy options.

PMID- 21099694
TI  - TRPV channel expression in human skin and possible role in thermally induced cell
      death.
AB  - Cell death via necrosis and apoptosis is a hallmark of deep dermal to full
      thickness cutaneous burn injuries. Keratinocytes might act as thermosensory cells
      that transmit information regarding ambient temperature via heat-gated transient
      receptor potential vanilloid (TRPV) ion channels. The aim of this study was to
      investigate the distribution of TRPV1, 2, 3, and 4 in uninjured and thermally
      burned skin. The authors investigated warmth-evoked currents in keratinocytes and
      cell kinetics of thermally injured keratinocytes in culture with agonists and
      antagonists of TRPV channels. Specimens of uninjured normal skin and discarded
      tissue of thermally injured skin were stained for TRPV1, 2, 3, and 4. Cultured
      primary human keratinocytes were heated for 5 minutes at the following
      temperatures: 37 degrees C (control), 42 degrees C, and 60 degrees C and
      thereafter cultured for 24 or 48 hours at 37 degrees C. Thermally stressed cells
      were treated with TRPV antagonists capsazepine or ruthenium red, and cell
      viability capacity was determined. TRPV1, TRPV2, TRPV3, and TRPV4
      immunoreactivity was differentially identified on basal and suprabasal
      keratinocytes of healthy human skin. Patch clamp analysis showed a functional
      response of human keratinocytes at temperatures >40 degrees C. Cell death of
      keratinocytes after heating at 42 degrees C was reduced by 15 and 5% with
      ruthenium red and by 20 and 30% by capsazepine at 24 and 48 hours, respectively.
      Cell death after treatment at 60 degrees C was significantly reduced at 24 hours
      with capsazepine (22%) or ruthenium red (18%) but only minimally affected after
      48 hours postinjury. Interaction with TRPV channels on keratinocytes may offer a
      new strategy to counteract cell death after thermal injury.

PMID- 21099695
TI  - Nurses' educational needs for pain management of post-cardiac surgery patients: a
      qualitative study.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Inadequate knowledge among health care
      providers is a key barrier to good pain management, and nurses have a major role
      to provide education to patients. The purpose of this study was to identify
      nurses' learning needs to prepare patients for managing pain before and after
      discharge home from cardiac surgery. The overall aim is to develop a pain
      education intervention for nurses working with cardiac surgical patients. SUBJECT
      AND METHODS: This was a focus groups study. Participants (N=22) were asked about
      their perceptions of patients' education needs for pain management after cardiac
      surgery and approaches to help nurses meet these needs. The Pain Beliefs Scale
      was used to capture nurses' own misbeliefs about pain that would need
      clarification in a successful pain education intervention. RESULTS: Nurses
      identified pain management challenges in the hospital, particularly related to
      patients' age, patient concerns about the use of opioids, the need to use
      multiple management strategies, and preparing patients to manage pain at home.
      Pain Beliefs Scale scores were low related to opioid dosing and adverse effects.
      Participants identified their most helpful educational approaches being brief in
      services, hands-on learning, lunch-and-learn sessions, and designated education
      days. CONCLUSION: Participants identified the most common pain knowledge gaps for
      patients before and after discharge after cardiac surgery. These data will be
      used to develop an education intervention for nurses to help their cardiac
      surgery patients with more effective pain management strategies before and after
      discharge home.

PMID- 21099696
TI  - Impact of prodromal symptoms on prehospital delay in patients with first-time
      acute myocardial infarction in Korea.
AB  - BACKGROUND: Information is limited concerning how affected individuals respond to
      early warning signs before their acute coronary event and how the presence of
      prodromal symptoms impacts prehospital delay. OBJECTIVES: This study's aim was to
      identify the characteristics and interpretation of prodromal symptoms in patients
      with a first-time acute myocardial infarction (AMI) and to determine whether the
      presence of prodromal symptoms was predictive of prehospital delay. SUBJECTS AND
      METHODS: This was a descriptive study using semistructured interview. A total of
      271 hospitalized patients diagnosed as having AMI were interviewed from November
      2007 to December 2008 at a university hospital in Korea. Patients were queried
      regarding whether they noticed a most troubling prodromal symptom prior to their
      acute cardiac event and how they responded to the symptom. RESULTS: Men (53.0%)
      and women (54.2%) experienced prodromal symptoms. Patients who reported prodromal
      symptoms were more likely to be older and to have no chest pain upon
      hospitalization than those with no prodromes. Many patients did not generally
      recognize the importance of their warning symptoms; only about 40% visited a
      clinic in response to any prodromal symptom. Logistic regression analyses
      revealed that the presence of prodromal symptoms was an independent predictor
      affecting prehospital delay of more than 3 hours and more than 12 hours.
      CONCLUSIONS: Recognizing prodromal symptoms as needing attention could be a
      trigger for patients to seek medical help earlier. Educational strategies should
      focus on improving awareness of prodromal symptoms of AMI, particularly in those
      with a family history or at high risk for cardiovascular disease.

PMID- 21099697
TI  - Implementation of a comprehensive interdisciplinary care coordination of infants
      and young children on Berlin Heart ventricular assist devices.
AB  - BACKGROUND: Young children supported on a ventricular assist device (VAD) can
      have prolonged hospitalizations awaiting heart transplantation. The adult VAD
      literature demonstrates that comprehensive programs optimize transplantation
      outcomes. The goal of this intervention was to create an interdisciplinary
      program to optimize care coordination and delivery in young children requiring a
      VAD. METHOD: This study was a case review. RESULTS: We have supported 8 infants
      and young children with Berlin Heart VAD. These children's hospitalizations have
      been more complex than those of our older VAD patients, and they have required
      intensive care for prolonged periods. An interdisciplinary group evaluated our
      practices and identified areas for potential improvement. The focus group from
      our intensive care unit introduced multiple interventions to optimize
      interdisciplinary care coordination and consistency of practice. These included
      (1) interdisciplinary care guidelines for chronically, critically ill patients;
      (2) institution of a primary cardiovascular intensive care unit (CVICU) physician
      and nurse practitioner system; (3) introduction of a psychological intervention
      for families to minimize the impact of their extended CVICU stay; (4)
      implementation of early jejunal feeds; (5) a focused developmental and
      rehabilitation protocol, 6) implementation of a structured approach to minimizing
      blood transfusions; (7) increased structure for our interdisciplinary rounds to
      optimize team communication; (8) comprehensive nursing education including wound
      care, anticoagulation management, and laboratory draws; and (9) a protocol for
      off-unit rehabilitative/developmental interventions. These changes in both
      practice and approach for young VAD patients have also been of benefit to other
      chronically, critically ill children in the CVICU, as well as to our CVICU team.
      CONCLUSION: Comprehensive interdisciplinary care coordination and standardized
      practice can be achieved in the critical care setting for complex pediatric heart
      failure patients who require long-term VAD support.

PMID- 21099699
TI  - Medication Discussion Questions (MedDQ): developing a guide to facilitate patient
      clinician communication about heart medications.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Adherence to evidence-based therapies has
      emerged as one of the great challenges of translating discoveries to clinical
      care to optimize patient outcomes. In particular, nonadherence to lifesaving
      medications continues to trouble health care systems. We conducted a series of
      studies to investigate why cardiac patients stop life-sustaining medications and
      to develop a tool to proactively address medication adherence issues. We could
      find no available preventive tools for communicating with patients about their
      medications in the clinical setting. In this article, we summarize the process of
      developing such a tool. SUBJECTS AND METHODS: We used a mixed-methods approach in
      a series of studies that included examining quantitative data from a large
      patient registry, conducting in-depth qualitative patient interviews, creating
      items representative of the qualitative findings, pilot testing items with heart
      patients, surveying an expert panel to establish content validity, and conducting
      in-depth interviews with health care providers to assess implementation
      opportunities. RESULTS AND CONCLUSIONS: Patient interviews revealed that
      patients' values and beliefs, barriers to treatment, and prior medication-taking
      behavior were of primary importance in understanding medication discontinuance.
      Pilot testing, expert panel review, and an implementation feasibility evaluation
      resulted in an 11-item communication guide to be used in a variety of health care
      settings. Clinicians need an efficient way of systematically communicating with
      patients about heart medications to identify barriers and to initiate preventive
      interventions when patients report barriers or challenges to medication
      adherence.

PMID- 21099698
TI  - Adequate health literacy is associated with higher heart failure knowledge and
      self-care confidence in hospitalized patients.
AB  - Heart failure (HF) patients with inadequate health literacy are at increased risk
      for poor self-care and negative health outcomes such as hospital readmission. The
      purpose of the present study was to examine the prevalence of inadequate health
      literacy, the reliability of the Dutch HF Knowledge Scale (DHFKS) and the Self
      care of Heart Failure Index (SCHFI), and the differences in HF knowledge, HF self
      care, and 30-day readmission rate by health literacy level among patients
      hospitalized with HF. The convenience sample included adults (n = 95) admitted to
      a large, urban, teaching hospital whose primary diagnosis was HF. Measures
      included the Short Test of Functional Health Literacy in Adults, the DHFKS, the
      SCHFI, and readmission at 30 days after discharge. The sample was 59 +/- 14 years
      in age, 51% male, and 67% African American; 35% had less than a high school
      education, 35% were employed, 73% lived with someone who helps with their HF
      care, and 16% were readmitted within 30 days of index admission. Health literacy
      was inadequate for 42%, marginal for 19%, and adequate for 39%. Reliability of
      the DHFKS and SCHFI scales was comparable to prior reports. Mean knowledge score
      was 11.43 +/- 2.26; SCHFI subscale scores were 56.82 +/- 17.12 for maintenance,
      63.64 +/- 18.29 for management, and 65.02 +/- 16.34 for confidence. Those with
      adequate health literacy were younger and had higher education level, HF
      knowledge scores, and HF self-care confidence compared with those with marginal
      or inadequate health literacy. Self-care maintenance and management scores and 30
      day readmission rate did not differ by health literacy level. These findings
      demonstrate the high prevalence of inadequate and marginal health literacy and
      that health literacy is an important consideration in promoting HF knowledge and
      confidence in self-care behaviors, particularly among older adults and those with
      less than a high school education.

PMID- 21099700
TI  - Cardiovascular risk factors in deployed service members with and without acute
      coronary syndromes.
AB  - BACKGROUND: Acute coronary syndromes (ACSs) occur in deployed military personnel,
      yet little is known about the cardiovascular (CV) risk profile of deployed US
      military service members who experience ACS. Stress and socioeconomic status
      (SES) as risk factors for ACS in service members deployed in ongoing Overseas
      Contingency Operations have not been considered. RESEARCH OBJECTIVE: To compare
      CV risk factors between service members who experienced ACS and healthy service
      members who did not experience ACS while deployed while controlling for
      nontraditional CV risk factors. SUBJECTS: Deployed service members who
      experienced ACS (n=93) and matched controls who did not experience ACS (n=137).
      METHODS: Healthy controls and ACS cases were matched on rank, area of operations,
      and ethnicity to control for confounding effects of SES, combat stress exposure,
      and ethnicity. RESULTS: Acute myocardial infarction occurred in 81.7% of the
      cases, and 18.3% had unstable angina. Most major CV risk factors were different
      between the 2 groups except blood sugar and history of dyslipidemia. In a
      univariate conditional logistic regression model, all CV risk factors except
      blood sugar were significant predictors of ACS. In a multivariate logistic
      regression model, older age (odds ratio [OR], 1.25; 95% confidence interval [CI],
      1.11-1.40), higher total cholesterol/high density lipoprotein cholesterol ratio
      (OR, 2.87; 95% CI, 1.65-4.97), and family history of premature coronary artery
      disease (OR, 4.83 [95% CI, 1.64-14.26]) independently predicted ACS in deployed
      service personnel. CONCLUSION: Controlling for SES, combat stress exposure, and
      ethnicity, traditional CV risk factors remain independent predictors of ACS in
      deployed service members.

PMID- 21099701
TI  - Familial pycnodysostosis: identification of a novel mutation in the CTSK gene
      (cathepsin K).
AB  - BACKGROUND: Pycnodysostosis, an autosomal recessive skeletal dysplasia, is
      characterized by short stature, osteosclerosis, delayed cranial suture closure,
      hypoplastic mandible, acro-osteolysis, hypoplastic clavicle, and dental
      anomalies. The disorder is caused by CTSK gene defects, a gene localized on 1q21.
      PURPOSE: To describe the clinical, radiological, and molecular findings in a
      family with pycnodysostosis. METHODS: The CTSK gene was analyzed from genomic DNA
      in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis
      and 100 healthy controls. RESULTS AND INTERPRETATION: We identified the novel
      homozygous mutation c.908G>A within exon 8 of the CTSK gene. This missense
      mutation leads to the substitution of the amino acid glycine at position 303 by
      glutamic acid (G303E) in cathepsin K protease. No genotype/phenotype correlation
      was present in affected members of the family with pycnodysostosis.

PMID- 21099703
TI  - Long-term excess mortality of 244 familial and 1502 sporadic one-year survivors
      of aneurysmal subarachnoid hemorrhage compared with a matched Eastern Finnish
      catchment population.
AB  - BACKGROUND: Saccular intracranial aneurysms (sIAs) develop in 2% of the
      population. Rupture of the sIA wall causes almost all cases of aneurysmal
      subarachnoid hemorrhage (aSAH). OBJECTIVE: We analyzed the long-term excess
      mortality of 244 familial and 1502 sporadic 1-year survivors of aSAH from sIA
      compared with a matched Eastern Finnish catchment population. METHODS: The Kuopio
      Neurosurgery Database contains 1746 one-year survivors of aSAH (1980-2007) from a
      defined population. The median follow-up time, until death (n = 494) or the end
      of 2008, was 12 years. Relative survival ratios were calculated compared with the
      matched (sex, age, calendar time) catchment population. Relative excess risk of
      death (RER) was estimated for variables known on admission for aSAH as well as
      Glasgow Outcome Scale score at 12 months. RESULTS: There was 12% excess mortality
      at 15 years (cumulative relative survival ratio: 0.88; 95% confidence interval:
      0.85-0.91). Independent risk factors were male sex (RER: 1.6), age older than 64
      years (RER: 2.9), ruptured basilar tip sIA (RER: 4.5), severe hydrocephalus on
      admission (RER: 3.6), no occlusive therapy (RER: 6.0), and Glasgow Outcome Scale
      scores of 2, 3, or 4 at 12 months (RER: 23, 4.1, 2.1, respectively), but not
      familial sIA disease. There were lethal rebleeds from 13 of the 1440 clipped
      sIAs, 2 of the 265 coiled sIAs, and 2 from the 17 nonoccluded sIAs, and 14 new
      lethal bleeds from other sIAs. CONCLUSION: The impact of both sporadic and
      familial aSAH and their sequelae in the central nervous and cardiovascular
      systems may cause long-term morbidity and mortality. The complex sIA disease may
      predispose to other vascular events later in life. The causes of the long-term
      excess mortality are heterogeneous, and more detailed analyses are required.

PMID- 21099704
TI  - Arachnoid cyst confined to the internal auditory canal-endoscope-assisted
      resection: case report and review of the literature.
AB  - BACKGROUND AND IMPORTANCE: An arachnoid cyst confined to the internal auditory
      canal is a rare condition. Different pathogeneses are discussed, and a
      progressive enlargement of the cysts has been reported. This case illustrates the
      beneficial aspect of endoscopic assistance in microsurgical resection of this
      lesion. CLINICAL PRESENTATION: A slowly progressive hearing loss developed in a
      35-year-old woman over 2 years; she reported experiencing tinnitus for 7 years.
      Magnetic resonance imaging revealed a cystic lesion in the internal auditory
      canal appearing hypointense on T1-weighted images and hyperintense on T2-weighted
      images, suggesting an arachnoid cyst. INTERVENTION: The cyst wall was fenestrated
      and partially resected in an endoscope-assisted microsurgical technique. Adherent
      vestibular nerve fibers in the cyst wall prevented total removal of the cyst. The
      histological examination confirmed the diagnosis of an arachnoid cyst.
      CONCLUSION: The endoscope-assisted microsurgical technique enables a safe cyst
      resection with good visualization of important neurovascular structures within
      the internal auditory canal. Small remnants of the capsule that are firmly
      attached to important neurovascular structures should be left in place rather
      than risk neurological deficits.

PMID- 21099705
TI  - Multiple epidural hematomas and hemodynamic collapse caused by a subgaleal drain
      and suction-induced intracranial hypotension: case report.
AB  - BACKGROUND AND IMPORTANCE: Subgaleal drains are commonly used in neurosurgery.
      Rare complications attributed to these drains have been described. We present a
      rare complication of hemodynamic collapse and multiple epidural hematomas
      attributed to intracranial hypotension induced by a subgaleal drain connected to
      suction during wound closure. CLINICAL PRESENTATION: A 3.5-year-old boy underwent
      an uneventful occipital lobectomy and titanium mesh cranioplasty for resection of
      a recurrent choroid plexus carcinoma. The child had undergone 2 uneventful
      previous resections and cranial irradiation. During skin closure, a subgaleal
      drain was connected to suction to keep the surgical bed dry. Immediately after
      completion of the subgaleal layer closure, there was an acute hemodynamic
      collapse, accompanied by bradycardia and a drop in the hematocrit. After
      successful resuscitation, the child underwent a brain computed tomography scan
      that showed a large bifrontal epidural hematoma and multiple additional small
      epidural hematomas. The large hematoma was surgically evacuated, and the child
      had an uneventful recovery. CONCLUSION: Acute negative intracranial hypotension
      may cause bradycardia, epidural hematomas, and hemodynamic collapse. Subgaleal
      drains should not be connected to suction systems, and care should be taken when
      these drains are connected to vacuum bulbs in high-risk cases such as after
      cranial irradiation, large resections, and mesh cranioplasties.

PMID- 21099706
TI  - Trying to define another application of hypothermia to acute spinal cord injury.

PMID- 21099707
TI  - Impact of tumor histology on resectability and neurological outcome in primary
      intramedullary spinal cord tumors: a single-center experience with 102 patients.
AB  - BACKGROUND: Surgical outcomes for intramedullary spinal cord tumors are affected
      by many variables including tumor histology and preoperative neurological
      function. OBJECTIVE: To analyze the impact of tumor histology on neurological
      outcome in primary intramedullary spinal cord tumors. METHODS: A retrospective
      review of 102 consecutive patients with intramedullary spinal cord tumors treated
      at a single institution between January 1998 and March 2009. RESULTS: Ependymomas
      were the most common tumors with 55 (53.9%), followed by 21 astrocytomas (20.6%),
      12 hemangioblastomas (11.8%), and 14 miscellaneous tumors (13.7%). Gross total
      resection was achieved in 50 ependymomas (90.9%), 3 astrocytomas (14.3%), 11
      hemangioblastomas (91.7%), and 12 miscellaneous tumors (85.7%). At a mean follow
      up of 41.8 months (range, 1-132 months), we observed recurrences in 4 ependymoma
      cases (7.3%), 10 astrocytoma cases (47.6%), 1 miscellaneous tumor case (7.1%),
      and no recurrence in hemangioblastoma cases. When analyzed by tumor location,
      there was no difference in neurological outcomes (P = .66). At the time of their
      last follow-up visit, 11 patients (20%) with an ependymoma improved, 38 (69%)
      remained the same, and 6 (10.9%) worsened. In patients with an astrocytoma, 1
      (4.8%) improved, 10 (47.6%) remained the same, and 10 (47.6%) worsened. One
      patient (8.3%) with a hemangioblastoma improved and 11 (91.7%) remained the same.
      No patient with a hemangioblastoma worsened. In the miscellaneous tumor group, 2
      (14.3%) improved, 10 (71.4%) remained the same, and 2 (14.3%) worsened.
      Preoperative neurological status (P = .02), tumor histology (P = .005), and
      extent of resection (P < .0001) were all predictive of functional neurological
      outcomes. CONCLUSION: Tumor histology is the most important predictor of
      neurological outcome after surgical resection because it predicts resectability
      and recurrence.

PMID- 21099709
TI  - The temporal profile of cerebral blood flow and tissue metabolites indicates
      sustained metabolic depression after experimental subarachnoid hemorrhage in
      rats.
AB  - BACKGROUND: Derangement of cerebral metabolism occurs after various insults such
      as ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH).
      OBJECTIVE: To investigate the course of cerebral blood flow and metabolic
      parameters in the first hours after experimental SAH. METHODS: Sixteen Sprague
      Dawley rats were subjected to SAH using the endovascular filament model or served
      as controls (8 rats in each group). Local cerebral blood flow and intracranial
      pressure were measured continuously. Microdialysis samples were acquired in 30
      minute intervals for 6 hours after SAH. Concentrations of glucose, lactate,
      pyruvate, and glutamate were determined. RESULTS: After induction of SAH,
      cerebral perfusion pressure and local cerebral blood flow sharply decreased. The
      decrease in local cerebral blood flow exceeded the decrease in cerebral perfusion
      pressure throughout the observation period. Glutamate concentrations in
      microdialysis samples increased sixfold and recovered to baseline levels. Lactate
      concentrations immediately increased after SAH, recovered incompletely, and
      remained above the levels of control animals until the end of the sampling
      period. Pyruvate concentrations showed a delayed increase starting 2 hours after
      SAH. CONCLUSION: The course of cerebral blood flow after SAH resembles global
      ischemia followed by a continuous low-flow state caused by a sudden decrease in
      cerebral perfusion pressure and acute vasoconstriction. The courses of lactate
      and pyruvate concentrations indicate a persistently deranged aerobic metabolism.

PMID- 21099708
TI  - Evaluation of the ShuntCheck noninvasive thermal technique for shunt flow
      detection in hydrocephalic patients.
AB  - BACKGROUND: ShuntCheck (Neuro Diagnostic Devices, Inc., Trevose, Pennsylvania) is
      a new device designed to detect cerebrospinal fluid (CSF) flow in a shunt by
      sensing skin temperature downstream from a region of CSF cooled by an ice cube.
      OBJECTIVE: To understand its accuracy and utility, we evaluated the use of this
      device during routine office visits as well as during workup for suspected shunt
      malfunction. METHODS: One hundred shunted patients were tested, including 48
      evaluated during possible shunt malfunction, of whom 24 went on to surgical
      exploration. Digitally recorded data were blindly analyzed and compared with
      surgical findings and clinical follow-up. RESULTS: Findings in the 20
      malfunctioning shunts with unambiguous flow or absence of flow at surgery were
      strongly correlated with ShuntCheck results (sensitivity and specificity to flow
      of 80% and 100%, respectively, P = .0007, Fisher's exact test, measure of
      agreement kappa = 0.8). However, the thermal determination did not distinguish
      patients in the suspected malfunction group who received surgery from those who
      were discharged without surgery (P = .248 by Fisher's exact test, kappa = 0.20).
      Half of the patients seen in routine office visits did not have detectable flow,
      although none required shunt revision on clinical grounds. Intermittent flow was
      specifically demonstrated in one subject who had multiple flow determinations.
      CONCLUSION: Operative findings show that the technique is sensitive and specific
      for detecting flow, but failure to detect flow does not statistically predict the
      need for surgery. A better understanding of the normal dynamics of flow in
      individual patients, which this device may yield, will be necessary before the
      true clinical utility of non-invasive flow measurement can be assessed.

PMID- 21099710
TI  - The association between weather and spontaneous subarachnoid hemorrhage: an
      analysis of 155 US hospitals.
AB  - BACKGROUND: A seasonal and meteorological influence on the incidence of
      spontaneous subarachnoid hemorrhage (SAH) has been suggested, but a consensus in
      the literature has yet to emerge. OBJECTIVE: This study examines the impact of
      weather patterns on the incidence of SAH using a geographically broad analysis of
      hospital admissions and represents the largest study of the topic to date.
      METHODS: We retrospectively analyzed SAH admissions to 155 US hospitals during
      the calendar years 2004 to 2008 (N = 7758). Daily weather readings for
      temperature, pressure, and humidity were obtained for the same period from
      National Oceanic and Atmospheric Administration weather stations located near
      each hospital. The daily values of each weather variable were associated with the
      daily volume of SAH admissions using a combination of correlation and time-series
      analyses. RESULTS: No seasonal trends were observed in the monthly volume of SAH
      admissions during the study period. No significant correlation was detected
      between the daily SAH admission volume and the day's weather, the previous day's
      weather, or the 24-hour weather change. CONCLUSION: This study represents the
      most comprehensive investigation of the association between weather and
      spontaneous SAH to date. The results suggest that neither season nor weather
      significantly influences the incidence of SAH.

PMID- 21099711
TI  - We still do not have a reliable and validated noninvasive technique that can
      provide an accurate quantitative measurement of intracranial pressure (ICP) that
      could replace invasive quantitative measurements of ICP.

PMID- 21099712
TI  - Footprint in brain.

PMID- 21099713
TI  - MacCarty keyhole.

PMID- 21099714
TI  - Surgical technique and outcomes in the treatment of spinal cord ependymomas: part
      II: myxopapillary ependymoma.
AB  - BACKGROUND: Myxopapillary ependymomas usually occur in the filum terminale of the
      spinal cord. OBJECTIVE: This report summarizes our experience treating
      myxopapillary ependymomas. METHODS: The records of 34 patients (14 men, 20 women;
      mean age 45.5 years; age range, 14-88 years) who underwent resection of a
      myxopapillary ependymoma between 1983 and 2006 were reviewed for age, sex, tumor
      location, symptoms at diagnosis, duration of symptoms, treatment before
      presentation, extent of surgical resection, adjuvant therapy, length of follow
      up, evidence of recurrence, and complications. Neurological examinations
      performed at presentation, immediately after surgery, and last follow-up were
      graded according to the McCormick grading scale. RESULTS: The average duration of
      symptoms before diagnosis was 22.2 months. The most common symptom was pain
      followed by weakness, bowel/bladder symptoms, and numbness. The rate of gross
      total resection was 80%. All patients with a subtotal resection (20%) underwent
      postoperative radiation therapy. Presentation and outcomes of patients who
      underwent subtotal resection followed by radiation therapy were compared with
      those who underwent gross total resection. There was no significant difference in
      neurological grade between the groups at presentation or final follow-up. The
      overall recurrence rate was 10% (3/34 patients). CONCLUSION: The goal of surgical
      treatment of myxopapillary ependymomas is resection to the greatest extent
      possible with preservation of function. In cases of subtotal resection,
      postoperative radiation therapy may improve outcome. If neurological function is
      maintained at treatment, these indolent lesions allow years of good function.

PMID- 21099715
TI  - Analysis of reoperation in mesial temporal lobe epilepsy with hippocampal
      sclerosis.
AB  - BACKGROUND: Most patients do well after epilepsy surgery for mesial temporal lobe
      sclerosis, and in only 8 to 12% of all operations, the outcome is classified as
      not improved. OBJECTIVE: To analyze the outcome of reoperation in cases of
      incomplete resection of mesial temporal lobe structures in patients with mesial
      temporal lobe sclerosis in temporal lobe epilepsy. METHODS: We analyzed 22
      consecutive patients who underwent reoperation for mesial temporal lobe sclerosis
      (follow-up, 23-112 months; mean, 43.18 months) by evaluating noninvasive
      electroencephalographic/video monitoring before the first and second surgeries
      (semiology, interictal epileptiform discharges, ictal electroencephalography with
      special attention to the secondary contralateral evolution of the
      electroencephalographic seizure pattern after the initial regionalization), and
      magnetic resonance imaging (resection indices after the first and second
      surgeries on the amygdala, hippocampus, lateral temporal lobe). In 18 of 22
      patients T2 relaxometry of the contralateral hippocampus was performed. RESULTS:
      Nine of 22 patients became seizure free; another 4 patients had a decrease in
      seizures and eventually became seizure free (range, 16-51 months; mean, 30.3).
      Recurrence of seizures is associated with (1) ictal electroencephalography with
      later evolution of an independent pattern over the contralateral temporal lobe (0
      of 5 patients seizure free vs 5 of 7 patients non-seizure free; P = .046) and (2)
      a smaller amount of lateral temporal lobe resection in the second surgery (1.06
      +/- 0.59 cm vs 2.18 +/- 1.37 cm; P = .019). No significant correlation with
      outcome was found for lateralization of interictal epileptiform discharges,
      change in semiology, other resection indices, T2 relaxometry, onset and duration
      of epilepsy, duration of follow-up, and side of surgery. CONCLUSION: Patients
      have a less favorable outcome with a reoperation if they show ictal scalp
      electroencephalography with secondary contralateral propagation and if only a
      small second resection of the lateral temporal lobe is performed.

PMID- 21099716
TI  - Risk factors for conversion to permanent ventricular shunt in patients receiving
      therapeutic ventriculostomy for traumatic brain injury.
AB  - BACKGROUND: Intracranial pressure is routinely monitored in patients with severe
      traumatic brain injury (TBI). Patients with TBI sometimes develop hydrocephalus,
      requiring permanent cerebrospinal fluid (CSF) diversion. OBJECTIVE: To quantify
      the need for permanent CSF diversion in patients with TBI. METHODS: Patients who
      received a ventriculostomy after TBI between June 2007 and July 2008 were
      identified, and their medical records were abstracted to a database. RESULTS:
      Sixteen of 71 patients (22.5%) receiving a ventriculostomy required a
      ventriculoperitoneal or ventriculoatrial shunt before discharge from the
      hospital. The average number of days between ventriculostomy and shunt was 18.3.
      Characteristics that predispose these patients to require permanent CSF diversion
      include the need for craniotomy within 48 hours of admission (odds ratio, 5.20;
      95% confidence interval, 1.48-18.35) and history of culture-positive CSF (odds
      ratio, 5.52; 95% confidence interval, 1.19-25.52). Length of stay was increased
      in patients receiving permanent CSF diversion (average length of stay, 61 vs 31
      days; P = .04). Patient discharge disposition was similar between shunted and
      nonshunted patients. CONCLUSION: In this retrospective study, 22% of TBI patients
      who required a ventriculostomy eventually needed permanent CSF diversion.
      Patients with TBI should be assessed for the need for permanent CSF diversion
      before discharge from the hospital. Care must be taken to prevent ventriculitis.
      Future studies are needed to evaluate more thoroughly the risk factors for the
      need for permanent CSF diversion in this patient population.

PMID- 21099718
TI  - Predifferentiated brain-derived adult human progenitor cells migrate toward
      ischemia after transplantation to the adult rat brain.
AB  - BACKGROUND: The adult human brain contains neural stem/progenitor cells (AHNPCs)
      that can survive transplantation into the adult rat brain, migrate toward a
      lesion, and display limited neuronal differentiation in vivo. OBJECTIVE: To
      investigate the effect of manipulating AHNPCs before grafting by
      predifferentiation, ie, initiating neuronal differentiation before
      transplantation, and to determine whether this cell priming would affect their
      ability to migrate in vivo. METHODS: AHNPCs were prepared from temporal lobe
      resections for epilepsy. Seven days after global brain ischemia,
      predifferentiated AHNPCs (exposed to basic fibroblast growth factor, heparin, and
      laminin) were transplanted to the left hippocampus. Four and 10 weeks after
      transplantation, brain sections were analyzed by immunohistochemistry. RESULTS:
      Transplanted primed cells expressed committed neuronal markers at a much earlier
      stage compared with nonprimed AHNPCs and were found colabeled with human markers
      within the damaged CA1 region 4 weeks after grafting. Furthermore,
      predifferentiated AHNPCs migrated preferentially into an ischemic lesion, similar
      to their undifferentiated counterparts. The chemoattractant effect from the
      expression of stromal cell-derived factor-1alpha (SDF-1alpha) in ischemic CA1 on
      AHNPCs expressing CXC chemokine receptor 4 (CXCR4) may explain this preference in
      migration in vivo. CONCLUSION: The plasticity of neural progenitors derived from
      the adult human brain may be greater than previously assumed in that manipulation
      before grafting may influence the phenotypes seen in vivo. The SDF-1alpha-CXCR4
      axis is involved in the targeted migration toward an ischemic lesion in the adult
      rat brain, similar to previous reports on endogenous progenitors in rats and
      grafted fetal human neural progenitors.

PMID- 21099717
TI  - Single-copy gain of chromosome 1q is a negative prognostic marker in pediatric
      nonependymal, nonpilocytic gliomas.
AB  - BACKGROUND: Reports of genetic analyses on pediatric gliomas are few, and those
      tumors have been far less characterized than adult gliomas. OBJECTIVE: To
      characterize the genetic and biological features of pediatric gliomas. METHODS:
      We investigated 23 pediatric nonependymal, nonpilocytic gliomas for chromosomal
      copy number aberrations (CNAs) by comparative genomic hybridization (CGH),
      mutations of isocitrate dehydrogenase (IDH) genes by direct sequencing, and
      proliferative activity and expression of O-methylguanine-DNA methyltransferase
      (MGMT) by immunohistochemistry. RESULTS: The most frequent CNA was single-copy
      gain of chromosome 1q, with 10 of 20 successfully investigated tumors showing the
      abnormality (50%). Other CNAs detected by CGH included gain on 7q (+7q) in 6, +9q
      in 5, +17q in 5, and + 7p in 4 cases. Gain of entire chromosome 7 was rare (2
      cases), and codeletion of 1p and 19q was not detected. Gain of 1q was
      significantly predictive for shorter progression-free survival (PFS) and overall
      survival (OS), and even more closely associated with poor clinical outcome than
      histological grade (P = .0009 for PFS, P = .003 for OS by 1q status; P = .004 for
      PFS, P = .035 for OS by high-grade vs low-grade). Gain of 1q was also
      significantly correlated with proliferative activity (P = .0002), and tumors with
      1q gain showed a trend toward higher MGMT expression (P = .27). Mutation of IDH1
      gene was detected in only 2 of 17 tumors successfully analyzed. CONCLUSION:
      Single copy gain of 1q is associated with biological features of pediatric
      gliomas, and is a negative prognostic marker in patients with those tumors.

PMID- 21099719
TI  - The next step: innovative molecular targeted therapies for treatment of
      intracranial chordoma patients.
AB  - BACKGROUND: Chordomas are rare, locally aggressive malignancies that often
      exhibit an insidious natural history and are difficult to eradicate. Surgery and
      radiotherapy are the treatment mainstays of chordoma, but the chance of local
      recurrence remains high. Patients who relapse or cannot undergo a complete en
      bloc resection generally have a poor prognosis. New agents for postoperative
      adjuvant treatment of chordomas are needed. OBJECTIVE: To highlight potential
      clinical trials that could evolve from new insights into the molecular biology of
      chordoma. METHODS: We performed a review of recent studies published in the
      literature that have begun to characterize the molecular features of chordoma,
      and with this knowledge, several targets for potential clinical therapies have
      been determined. RESULTS: Several receptor tyrosine kinases and their downstream
      signaling cascades show dysregulation in chordoma and represent attractive
      targets for future therapeutic interventions. The pathways shown to be of
      particular importance in chordoma involve the platelet-derived growth factor
      receptor, epidermal growth factor receptor, hepatocyte growth factor receptor,
      and common downstream cascade of phosphoinositide 3-kinases, Akt, and mammalian
      target of rapamycin. CONCLUSION: Recent findings characterizing the molecular
      biology of chordoma have illuminated multiple possible targets for future
      clinical trials. The availability of inhibitors against these aberrant pathways
      makes clinical trials with chordoma both feasible and immediately realizable.
      Additionally, we emphasize the rationale for combination therapy when
      implementing molecular therapy in chordoma and other cancers.

PMID- 21099720
TI  - Stent placement for atherosclerotic stenosis of the vertebral artery ostium:
      angiographic and clinical outcomes in 117 consecutive patients.
AB  - BACKGROUND: Although it is thought to be a safe treatment option, the main
      concerns related to treating vertebral artery ostium (VAO) stenosis with stents
      have been the rate of restenosis and the uncertain long-term results. OBJECTIVE:
      To evaluate the angiographic and clinical results of stent placement for
      atherosclerotic stenosis of the VAO. METHODS: One hundred seventeen consecutive
      patients with atherosclerotic VAO stenosis were treated with stent placement over
      a period of 12 years. All patients were retrospectively analyzed through the use
      of a prospectively collected database. The indication criteria for this treatment
      protocol were symptomatic severe VAO stenoses (> 60%) and asymptomatic severe VAO
      stenoses (> 60%) with incidentally detected infarction in the posterior
      circulation. The target diameter of stent dilatation from 1997 to 2000 was the
      normal vessel diameter just distal to the lesion. Moderate overdilation in the
      proximal portion of the stents has been performed since 2001. RESULTS: Successful
      dilatation was obtained in 116 of 117 cases. Transient neurological complications
      developed in 2 patients; however, no patients experienced any permanent
      neurological complications. One hundred four patients underwent follow-up
      angiography at 6 months after stenting. The restenosis rate at the 6-month follow
      up was 9.6% (10 of 104). Until 2000, the restenosis rate after stenting was
      13.3%. Since 2001, the restenosis rate has decreased to 4.5%. The median clinical
      follow-up period was 48 months. The annual rate of strokes in the posterior
      circulation was 0.95%. CONCLUSION: Stent placement for atherosclerotic VAO
      stenosis is considered to be a feasible and safe treatment and may be effective
      for stroke prevention. The moderate overdilation of stents may be an effective
      modality for the prevention of restenosis.

PMID- 21099721
TI  - Treatment of vertebral hemangiomas with absolute alcohol (ethanol) embolization,
      cord decompression, and single level instrumentation: a pilot study.
AB  - BACKGROUND: Vertebral hemangiomas (VH) are the most common lesions of the
      vertebral column. OBJECT: To evaluate the role of intraoperative ethanol
      embolization, surgical decompression, and instrumented fusion in VH presenting
      with myelopathy. METHODS: This is was a prospective study of single-level
      symptomatic VH with cord compression. Exclusions were as follows: pathological
      fractures, deformity, or multilevel pathologies. Surgery consisted of
      intraoperative bilateral pedicular absolute alcohol injection and laminectomy at
      the level of pathology followed by a short-segment instrumented fusion using
      pedicle screws. RESULTS: Ten patients (mean, 26.8 +/- 18.11; range, 10-68 years;
      8 females) were treated with use of this technique. Clinical features included
      myelopathy with motor and sensory involvement in all (4 paraplegic), sphincter
      involvement (8), and severe local pain (5). The preoperative American Spinal
      Injury Association (ASIA) scores were A (3), B (1), and C (6). All had pan
      vertebral body VH with severe cord compression. The mean surgical time was 102 +/
      22 minutes; average blood, 296 +/- 90.82 mL. Mean amount of absolute alcohol
      injected was 12.6 +/- 4.7 mL (1 requiring 25 mL). Immediate embolization was
      achieved in all patients allowing laminectomy and soft-tissue hemangioma removal.
      Postsurgery, all patients showed improvement (sphincters improved in 4) at a
      follow-up ranging 12 to 26 months (transient neurological deterioration in 1).
      Postsurgery ASIA scores were D (5) and E (5) at last follow-up. Two patients
      showed evidence of bone sclerosis on follow-up CT scans at 1.2 and 1.5 years.
      CONCLUSION: This procedure seems to be a safe, efficient method to treat VH with
      severe cord compression. It seems to serve the purpose of providing embolization,
      cord decompression, and rigid fusion at the same sitting.

PMID- 21099722
TI  - Natural history of hearing deterioration in intracanalicular vestibular
      schwannoma.
AB  - BACKGROUND: Intracanalicular vestibular schwannomas have a range of treatment
      options that can preserve hearing: microsurgery, stereotactic radiotherapy, and
      conservative observation. OBJECTIVE: To evaluate the natural course of hearing
      deterioration during a period of conservative observation. METHODS: A
      retrospective case review was performed on 47 patients with a unilateral
      intracanalicular vestibular schwannoma. Evaluation of growth was monitored by
      repeat MRI scanning. Repeated pure-tone and speech audiometry results were
      evaluated for subgroups of patients showing growth or no growth and by subsite
      location of tumor in the internal auditory canal. RESULTS: Patients had a mean
      follow-up of 3.6 years. Over the entire population, the pure-tone average
      thresholds at 0.5, 1, 2, and 3 kHz and the word recognition scores both
      significantly deteriorated from 38 to 51 dB HL, and from 66% to 55%,
      respectively. Overall, 74% of subjects with good hearing, according to the 50/50
      rule, maintained hearing above this rule. There were no significant differences
      in hearing loss by subsite in the internal auditory canal (porus, fundus,
      central) or by growth status (stable, growing, shrinking). Only 6 patients showed
      a large hearing change. This happened early during follow-up, with relatively
      stable hearing after this. CONCLUSION: Hearing will deteriorate in some
      intracanalicular vestibular schwannomas, regardless of tumor growth. Hearing
      deterioration, if on a large scale, most likely occurs early in follow-up. The
      present results using conservative management in these tumors appear similar to
      those reported for stereotactic radiotherapy or microsurgery.

PMID- 21099723
TI  - Association between carotid atherosclerosis plaque with high signal intensity on
      T1-weighted imaging and subsequent ipsilateral ischemic events.
AB  - BACKGROUND: An association between magnetic resonance imaging detection of
      intraplaque hemorrhage and the risk of cerebral ischemic events has been
      described. However, few studies have followed patients with intraplaque
      hemorrhage. OBJECTIVE: We used 3-dimensional gradient-echo black-blood T1
      weighted imaging (screening BB [S-BB]) as a magnetic resonance imaging sequence
      to evaluate acute cerebrovascular stroke. The association between S-BB high
      signal plaques and the risk of subsequent ipsilateral ischemic events was
      investigated. METHODS: A total of 928 consecutive patients hospitalized for a
      stroke or transient ischemic attack according to the Trial of Org 10172 in Acute
      Stroke Treatment (TOAST) classification were evaluated. Recurrence was
      retrospectively evaluated in S-BB-positive patients and patients with severe
      stenosis (SS) (>=70%) by magnetic resonance angiography. Based on clinical and
      imaging findings, recurrence was defined as a carotid artery stroke or transient
      ischemic attack that developed after hospital discharge as an initial event.
      RESULTS: Sixty-six patients were S-BB positive and 62 patients had severe
      stenosis (S-BB positive with SS, 32 patients; S-BB negative with SS, 30 patients;
      S-BB positive without SS, 34 patients). During a mean follow-up period of 9.1
      months, 7 S-BB-positive patients with SS (18.7%) and 1 S-BB-negative patient with
      SS (3%) had a recurrent event (P = .051). In the S-BB-positive group, in 34
      patients without SS, the recurrence rate was 14.7% (5/34); the difference in the
      recurrence rate between S-BB-positive group with and without SS was not
      significant (P = .34). CONCLUSION: Patients with carotid artery lesions and
      intraplaque hemorrhage tend to be at higher risk of a subsequent ipsilateral
      ischemic event. Risk evaluation of carotid artery disease should include plaque
      characteristics.

PMID- 21099724
TI  - Korbinian Brodmann (1868-1918) and his contributions to mapping the cerebral
      cortex.
AB  - Korbinian Brodmann is best remembered for his classification of cortical areas
      based on cytoarchitecture. He was influenced by such greats as Alzheimer, Vogt,
      Edinger, Nissl, and Weigert. Although first presented in 1903, Brodmann's
      "mapping" continues to be the lingua franca of cortical localization and his
      writings on this topic have become neurological classics. Many of his areas have
      gone on to be associated with various nervous functions such as hearing (areas 41
      and 42) and vision (areas 17 and 18). Few textbooks of neurology, neuroanatomy,
      or neurosurgery fail to mention the important maps produced by Brodmann that are
      still used today. The present article discusses the life and influence of
      Korbinian Brodmann on our understanding of the human brain.

PMID- 21099725
TI  - Prednisolone in Bell's palsy related to treatment start and age.
AB  - OBJECTIVE: To evaluate if treatment start and age are related to the outcome in
      Bell's palsy patients treated with prednisolone. STUDY DESIGN: Prospective,
      randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Sixteen
      otorhinolaryngologic centers in Sweden and 1 in Finland. PATIENTS: Data were
      collected from the Scandinavian Bell's palsy study. A total of 829 patients were
      treated within 72 hours of onset of palsy. Follow-up was 12 months. INTERVENTION:
      Patients were randomly assigned to treatment with placebo plus placebo (n = 206),
      prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or
      prednisolone plus valacyclovir (n = 206). MAIN OUTCOME MEASURES: Facial function
      was assessed with the Sunnybrook grading system, and complete recovery was
      defined as Sunnybrook = 100. Time from onset of palsy to treatment start was
      registered. RESULTS: Patients treated with prednisolone within 24 hours and 25 to
      48 hours had significantly higher complete recovery rates, 66% (103/156) and 76%
      (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p
      = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours
      of palsy onset, there were no significant differences. Patients aged 40 years or
      older had significantly higher complete recovery rates if treated with
      prednisolone, whereas patients aged younger than 40 years did not differ with
      respect to prednisolone treatment. However, synkinesis was significantly less in
      patients younger than 40 years given prednisolone (p = 0.002). CONCLUSION:
      Treatment with prednisolone within 48 hours of onset of palsy resulted in
      significantly higher complete recovery rates and less synkinesis compared with no
      prednisolone.

PMID- 21099726
TI  - OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic
      disorders.
AB  - HYPOTHESIS: To investigate whether OTO-104, a poloxamer-based hydrogel containing
      micronized dexamethasone for intratympanic delivery, can provide long-lasting
      inner ear exposure and be well tolerated. METHODS: OTO-104 was administered
      intratympanically to guinea pigs and sheep, and its pharmacokinetic and toxicity
      profiles were examined. RESULTS: After a single intratympanic injection of OTO
      104 (from 0.6% to 20%, w/w), significant and prolonged exposure to dexamethasone
      in the inner ear was observed. Increasing the concentration of OTO-104 resulted
      in higher perilymph drug levels as well as a more prolonged duration of exposure.
      At the highest dose, therapeutic perilymph levels of dexamethasone could be
      sustained over 3 months in guinea pigs and more than 1 month in sheep. A
      toxicologic evaluation was conducted, including assessments of middle and inner
      ear function and physiology, as well as appraisal of local and systemic toxicity.
      A small and transient shift in hearing threshold was observed, most probably
      conductive in nature. No significant histologic changes in middle or inner ear
      tissues were noted. Although macroscopically mild erythema/inflammation was
      documented in a subset of guinea pigs treated with 20% OTO-104, the nature and
      the severity of these changes were not different between the poloxamer vehicle,
      saline, and 20% OTO-104 groups. No evidence of acute dermal toxicity, delayed
      hypersensitivity, or systemic adverse effects was found. CONCLUSION: OTO-104 is a
      novel proprietary therapeutic delivery system that can achieve prolonged,
      sustained release of dexamethasone within the inner ear fluids. The
      administration of this clinical candidate formulation via intratympanic injection
      is expected to be well tolerated both locally and systemically.

PMID- 21099728
TI  - A case of poor penmanship: foreign body in the vestibule.

PMID- 21099727
TI  - Hearing results after hypotympanotomy for glomus tympanicum tumors.
AB  - OBJECTIVE: We postulate, that glomus tympanicum tumors (GTTs) may be safely
      removed without interference with the ossicular chain via a hypotympanotomy
      approach. STUDY DESIGN: Prospective, nonrandomized anatomic and clinical study.
      SETTING: Tertiary referral center. PATIENTS: All 17 patients between 1989 and
      2009 with GTTs without involvement of the lumen of the jugular bulb.
      INTERVENTIONS: We used a modified hypotympanotomy approach. Our technique is a
      modification of the one first published by Shambaugh (1955). Pure-tone audiograms
      were performed in all patients. Preoperative and postoperative audiograms were
      modeled in a linear mixed model evaluating hearing threshold for air and bone
      conduction and air-bone gap at 500, 1,000, 2,000, and 3,000 Hz. In an effort to
      preserve the normal sound conducting apparatus and hearing, we used a
      retroauricular approach, exposing widely the jugular bulb, the carotid artery,
      the protympanum, and even the bony part of the Eustachian tube via a
      hypotympanotomy. Three formalin-fixed and one macerated temporal bones were
      dissected step by step under the operating microscope to demonstrate the approach
      in cadaver dissections. MAIN OUTCOME MEASURE: To evaluate if GTTs can be
      completely resected without interference with the ossicular chain to improve
      conductive hearing loss. RESULTS: We found a substantial improvement of hearing
      threshold after surgery at all frequencies in air conduction. For bone
      conduction, there was only a slight gain within random variation. The air-bone
      gap decreased significantly after surgery. CONCLUSION: Our approach demonstrated
      a safe avenue for complete tumor removal without interference with the continuity
      of the ossicular chain.

PMID- 21099729
TI  - Late failure rate of hearing preservation after middle fossa approach for
      resection of vestibular schwannoma.
AB  - OBJECTIVE: To explore the long-term hearing results after a middle fossa approach
      for resection of vestibular schwannoma. STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary referral center. PATIENTS: All patients undergoing a middle
      fossa approach for resection of vestibular schwannoma at a single institution
      with intent to preserve hearing between December 1989 and December 2009 were
      included in the study population. INTERVENTIONS: Standard middle fossa approach
      for resection of vestibular schwannoma, magnetic resonance imaging (MRI), and
      audiogram. MAIN OUTCOME MEASURES: Recurrence of tumor as evaluated by MRI and
      hearing results as measured by serial audiograms. RESULTS: Seventy-eight patients
      were identified who met study criteria. Fifty-one (65%) of the 78 patients had
      usable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO
      HNS] class A or B) postoperatively. Forty-four patients with successful hearing
      preservation had follow-up beyond their initial postoperative visit. Five (11%)
      of the 44 patients showed late degradation to nonserviceable hearing (AAO-HNS
      class C or D) over a mean follow-up of 4.0 years. Kaplan-Meier estimate of
      preservation of class A or B hearing at 10 years was 72%. Of the five patients
      with late degradation in hearing, 2 were found to have recurrences of their
      original tumor on MRI. There were 5 confirmed recurrences in the total study
      population. CONCLUSION: Late degradation of hearing was an infrequent occurrence
      after initially successful hearing preservation. When hearing degradation did
      occur, there seemed to be a correlation with tumor recurrence.

PMID- 21099730
TI  - Unilateral centrifugation: utricular assessment and protocol comparison.
AB  - OBJECTIVE: The purpose of this study was to examine how 2 different methods of
      lateral translation affect subjective visual vertical (SVV), ocular torsion
      position, and symptoms of nausea in a healthy population. STUDY DESIGN:
      Prospective study. SETTING: Tertiary referral center. PATIENTS: Eleven healthy
      control subjects ranging between 26 and 48 years of age with normal hearing
      sensitivity and no history of balance disorders, dizziness, or neurologic
      involvement. INTERVENTION(S): Subjects underwent 2 types of lateral translation:
      1) lateral translation followed by rotation, and 2) lateral translation during
      rotation. The order of lateral translation type and order of translation were
      randomized to avoid an order effect. MAIN OUTCOME MEASURE(S): Ocular torsion and
      SVV deviation were measured during each lateral translation trial. A visual
      analog scale was used to assess each participant's level of nausea before and
      directly after each lateral translation trial. RESULTS: There was no significant
      difference in ocular torsion, SVV deviation, or level of nausea between the 2
      methods. Both ocular torsion and SVV deviation were symmetrical to the right and
      left within both methods, and both demonstrated a linear relationship with the
      gravito-inertial acceleration vector. CONCLUSION: Both ocular torsion and SVV
      have been shown to offset systematically in response to unilateral utricular
      stimulation regardless of the lateral translation method used, with no
      significant difference in subjective sensations of nausea.

PMID- 21099731
TI  - Estrogen receptor expression in sporadic vestibular schwannomas.
AB  - HYPOTHESIS: We hypothesize that vestibular schwannomas (VSs) exhibit up
      regulation of estrogen receptor (ER) at the protein level compared with control
      great auricular nerve (GAN). BACKGROUND: It has been reported in the literature
      that VS occur more commonly in women and tend to be larger and more vascular in
      women, and growth rate can accelerate during pregnancy. The literature contains
      widely divergent results on ER expression in VS, however, varying from no
      detectable levels to detection of ER in all samples. METHODS: Sixteen sporadic VS
      specimens were immediately snap-frozen after microsurgical excision and analyzed
      for phosphorylated and total levels of ERalpha with Western blot analysis.
      ERalpha expression levels were normalized to actin; then, relative expression to
      GAN was determined. RESULTS: All VS specimens exhibited expression of both
      phosphorylated and total ERalpha. Total ERalpha expression in VS is equivalent to
      or slightly up-regulated compared with GAN. VS specimens exhibited more
      pronounced up-regulation of phosphorylated (i.e., activated) levels of ERalpha
      compared with GAN. CONCLUSION: We have demonstrated that ERalpha expression in VS
      is equivalent to GAN. The phosphorylated form of the receptor is up-regulated
      compared with GAN, however, indicating a higher level of ERalpha activation in
      sporadic VS compared with normal nerve. Further investigation into antiestrogen
      therapy for VS is warranted.

PMID- 21099732
TI  - Google it: obtaining information about local STD/HIV testing services online.
AB  - BACKGROUND: Although the Internet is one of the most commonly accessed resources
      for health information, finding information on local sexual health services, such
      as sexually transmitted disease (STD) testing, can be challenging. Recognizing
      that most quests for online health information begin with search engines, the
      purpose of this exploratory study was to examine the extent to which online
      information about local STD/HIV testing services can be found using Google.
      METHODS: Queries on STD and HIV testing services were executed in Google for 6
      geographically unique locations across the United States. The first 3 websites
      that resulted from each query were coded for the following characteristics: (1)
      relevancy to the search topic, (2) domain and purpose, (3) rank in Google
      results, and (4) content. RESULTS: Websites hosted at .com (57.3%), .org (25.7%),
      and .gov (10.5%) domains were retrieved most frequently. Roughly half of all
      websites (n = 376) provided information relevant to the query, and about three
      quarters (77.0%) of all queries yielded at least 1 relevant website within the
      first 3 results. Searches for larger cities were more likely to yield relevant
      results compared with smaller cities (odds ratio [OR] = 10.0, 95% confidence
      interval [CI] = 5.6, 17.9). On comparison with .com domains, .gov (OR = 2.9, 95%
      CI = 1.4, 5.6) and .org domains (OR = 2.9, 95% CI = 1.7, 4.8) were more likely to
      provide information of the location to get tested. DISCUSSION: Ease of online
      access to information about sexual health services varies by search topic and
      locale. Sexual health service providers must optimize their website placement so
      as to reach a greater proportion of the sexually active population who use web
      search engines.

PMID- 21099733
TI  - Assessment of fully and partially condom-protected sex among US women: the
      potential for overestimating protected sex acts.
AB  - Limited information is available on potential over-reporting of protected sex
      acts among US women. Of 19,003 sex acts reported by 705 participants over a 3
      month period, 26.9% and 9.2% were fully and partially protected by a condom,
      respectively. The potential for misclassifying partially condom-protected sex
      acts as fully condom-protected sex acts is discussed.

PMID- 21099734
TI  - Repeat syphilis among men who have sex with men--San Diego County, 2004-2009.
AB  - Among 614 men who have sex with men in San Diego County with early syphilis
      during January 2004 to June 2007, 74 (11.7%; 95% confidence interval: 9.3%-14.4%)
      had repeat syphilis within 2 years. HIV-infected MSM were more likely to have
      repeat syphilis (odds ratio: 1.9; 95% confidence interval: 1.1, 3.4).

PMID- 21099736
TI  - Cervical multilevel intraspinal stem cell therapy: assessment of surgical risks
      in Gottingen minipigs.
AB  - STUDY DESIGN: Assessment of long-term surgical risks from multiple intraspinal
      cell injections. OBJECTIVE: To prove that multilevel-targeted cell injection to
      the spinal cord can be a feasible and safe procedure. SUMMARY OF BACKGROUND DATA:
      Neural cell transplantation has been proposed as a treatment for a variety of
      neurologic disorders, including degenerative, ischemic, autoimmune, and traumatic
      etiologies. Among these diseases, the lack of effective treatment for amyotrophic
      lateral sclerosis has prompted the search for cell-based neuroprotection or motor
      neuron-replacement therapies. METHODS: Fifteen female minipigs, divided into 3
      experimental groups, underwent either 5 or 10 unilateral injections of neural
      stem cells or 10 vehicle injections into the C3-C5 segments of the spinal cord,
      using a device and technique developed for safe and accurate injection into the
      human spinal cord. All animals received intravenous Tacrolimus (0.025 mg/kg) BID
      during the course of the study. Sensory and motor functions as well as general
      morbidity were assessed for 28 days. Full necropsy was performed and spinal cords
      were analyzed for graft survival. This study was performed under Good Laboratory
      Practice conditions. RESULTS: Neither mortality nor permanent surgical
      complications were observed within the 28-day study period. All animals returned
      to preoperative baseline showing full motor function recovery. Graft survival was
      demonstrated by immunohistochemistry. CONCLUSION: Clinically acceptable neural
      progenitor survival, distribution, and density were achieved using the number of
      injections and surgical techniques specifically developed for this purpose.

PMID- 21099735
TI  - Management patterns in acute low back pain: the role of physical therapy.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the relationship
      between early physical therapy (PT) for acute low back pain and subsequent use of
      lumbosacral injections, lumbar surgery, and frequent physician office visits for
      low back pain. SUMMARY OF BACKGROUND DATA: Wide practice variations exist in the
      treatment of acute low back pain. PT has been advocated as an effective treatment
      in this setting although disagreement exists regarding its purported benefits.
      METHODS: A national 20% sample of the Centers for Medicare and Medicaid Services
      physician outpatient billing claims was analyzed. Patients were selected who
      received treatment for low back pain between 2003 and 2004 (n = 439,195). To
      exclude chronic low back conditions, patients were excluded if they had a prior
      visit for back pain, lumbosacral injection, or lumbar surgery within the previous
      year. Main outcome measures were rates of lumbar surgery, lumbosacral injections,
      and frequent physician office visits for low back pain during the following year.
      RESULTS: Based on logistic regression analysis, the adjusted odds ratio for
      undergoing surgery in the group of enrollees that received PT in the acute phase
      (<4 weeks) compared to those receiving PT in the chronic phase (>3 months) was
      0.38 (95% confidence interval [CI], 0.360.41), adjusting for age, sex, diagnosis,
      treating physician specialty, and comorbidity. The adjusted odds ratio for
      receiving a lumbosacral injection in the group receiving PT in the acute phase
      was 0.46 (95% CI, 0.44-0.49), and the adjusted odds ratio for frequent physician
      office usage in the group receiving PT in the acute phase was 0.47 (95% CI, 0.44
      0.50). CONCLUSION: There was a lower risk of subsequent medical service usage
      among patients who received PT early after an episode of acute low back pain
      relative to those who received PT at later times. Medical specialty variations
      exist regarding early use of PT, with potential underutilization among generalist
      specialties.

PMID- 21099737
TI  - Temporal and Spatial Expression of BMPs and BMP Antagonists During Posterolateral
      Lumbar Fusion.
AB  - STUDY DESIGN: Quantitative gene expression analysis and immunohistochemistry were
      used to investigate the temporal and spatial expression of bone morphogenic
      proteins (BMPs) and BMP antagonists in a posterolateral spine fusion model in
      rabbits. OBJECTIVE: To identify the expression pattern of BMPs and BMP
      antagonists and to determine the molecular and histologic changes of the graft
      and surrounding tissue during fusion. SUMMARY OF BACKGROUND DATA: There are no
      studies on BMP antagonists during spinal fusion. Furthermore, the reciprocal
      interaction between bone grafts and surrounding tissue is still unknown in
      fusion. METHODS: Eighteen New Zealand White rabbits underwent bilateral
      posterolateral spine fusion with autogenous bone graft. Rabbits were killed at 1,
      2, 4, or 6 weeks after arthrodesis. The spinal fusions were analyzed by
      radiography. On the right side, specimens were collected from the outer zone over
      the transverse processes, the inner zone between the transverse processes, muscle
      surrounding bone grafts, and the transverse process. Gene expression of BMP-2,
      BMP-4, and BMP-7, noggin, chordin, Sox9, and Runx2 were measured by real-time
      polymerase chain reaction at each time point of each sample. On the left side,
      molecules of interest were evaluated by immunohistochemistry on tissue sections.
      RESULTS: BMP-2, BMP-4, and BMP-7, noggin, and chordin were colocalized in rimming
      osteoblasts, osteoclasts, and chondrocytes. The outer zone demonstrated earlier
      bone maturation and faster increase in BMP gene expression than the inner zone.
      Muscle surrounding bone grafts showed significantly higher BMP expression and
      Runx2 activity at the early phase. BMP-positive cells were also noted around
      blood vessels. CONCLUSION: The colocalization and temporal relationship of BMPs
      and BMP antagonists suggests that BMP activity is tightly regulated by the
      antagonists during fusion. In addition, not only the decorticated transverse
      process, but also muscle surrounding bone grafts, is actively involved in
      osteogenesis during fusion.

PMID- 21099738
TI  - Diffusion magnetic resonance imaging to differentiate degenerative from
      infectious endplate abnormalities in the lumbar spine.
AB  - STUDY DESIGN: A retrospective observational study of healthy volunteers and
      patients with degenerative and infectious endplate abnormalities in the lumbar
      spine. OBJECTIVES: Our purpose was to evaluate the usefulness of diffusion
      weighted imaging (DWI) for the differentiation of degenerative and infectious
      endplate abnormalities using 1.5-T magnetic resonance imaging (MRI). SUMMARY OF
      BACKGROUND DATA: DWI can provide valuable structural information about tissues
      that may be useful for clinical applications in differentiation between
      degenerative and infectious endplate abnormalities. METHODS: Sixteen consecutive
      patients with endplate abnormalities that was detected by MRI of the lumbar
      spine, and 15 healthy volunteers were studied. DWI was performed using whole-body
      imaging with background body signal suppression with a b value of 1000 s/mm2.
      Apparent diffusion coefficient values of normal and abnormal vertebral bone
      marrow were calculated. RESULTS: Twenty-nine vertebral abnormalities were found
      in 16 patients. Nine vertebral abnormalities in 5 patients were because of
      infections and 20 vertebral abnormalities in 11 patients were because of
      degenerative changes; 7 levels were classified as Modic type 1, 7 levels as type
      2, and 6 levels as type 3. DWI showed hyperintensity in all patients with
      infection, similar to that used in positron emission tomography, but not in the
      intervertebral spaces of any patients with degenerative disease. Apparent
      diffusion coefficient values of infectious bone marrow were significantly higher
      than normal and degenerative bone marrow. CONCLUSION: DWI is useful for
      differentiation of degenerative and infectious endplate abnormalities. Moreover,
      MRI is widely used clinically because of the lack of ionizing radiation, low
      cost, and fast imaging time as compared with positron emission tomography.
      Therefore, DWI has the potential to be used as a screening tool.

PMID- 21099739
TI  - The thickness of skull at the halo pin insertion site.
AB  - STUDY DESIGN: The thickness of 415 skulls of Thai population was measured at the
      areas where halo pins are placed. OBJECTIVE: Analysis of skull thickness at the
      area of halo pin insertion site. SUMMARY OF BACKGROUND DATA: Halo orthosis is a
      device used for providing stable fixation of instability of cervical spine
      injury. Although this device can be applied quickly and safely, complications do
      occur. While clinical experiences have informed us that cranial bone thickness
      varies with age. METHODS: Coronal computerized tomography scans of 415 heads of
      patients who had no head injury, skull fracture, or craniofacial abnormalities
      were reviewed. All scans were performed with a Philips CX/Q. The patients' ages
      were between 15 days and 89 years. Measurements were taken directly from the
      computer console, using the measure mode function. These measurements were
      obtained in millimeters at the locations where halo pins would normally be
      placed. Statistical analyses within and between all age groups were performed
      using analysis of variance tests. RESULTS: The skull thickness increased with age
      at all sites measured. The average thickness of skull at the anterior midline
      varied from 5.62 mm (0-9 years) to 7.42 mm (80-89 years). The average thickness
      of the anterolateral was from 5.52 to 8.54 mm, and the average thickness of the
      posterolateral was from 5.59 to 8.86 mm. CONCLUSION: The thickness of skull at
      the halo pin insertion site gradually increases with age. Our study reveals that
      the thickness of skull reaches a steady peak in third to sixth decades. The
      thickness of skull at the anterior midline can be predicted by a simple linear
      regression equation: A = 7.302 + 0.014*age.

PMID- 21099740
TI  - The pharmacokinetics of enteric-coated mycophenolate sodium and its
      gastrointestinal side effects in de novo renal transplant recipients of Hispanic
      ethnicity.
AB  - OBJECTIVE: The aim of the study is to characterize the pharmacokinetics and the
      gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC
      MPS) in de novo kidney transplant patients of Hispanic ethnicity. MATERIALS AND
      METHODS: The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney
      transplant patients of Hispanic ethnicity. Eight blood samples were obtained
      after EC-MPS was given at the steady state. Blood concentrations of mycophenolic
      acid (MPA) and its glucuronide metabolite (MPAG) were measured. RESULTS: The mean
      age (+/- standard deviation) was 39.4 (+/- 12.3) years. The mean daily dose of EC
      MPS at the time of the pharmacokinetic study was 1408 +/- 108 mg. For MPA and
      MPAG, the time to peak concentration was 2.5 +/- 1.3 hours and 4.6 +/- 3.1 hours,
      respectively; the peak concentration (Cmax) was 19.3 +/- 17.2 mg/L and 109.4 +/-
      49.2 mg/L; and the area under the curve from 6 to 12 hours (AUC6-12) was 32.2 +/-
      19.3 mg.hr/L and 373.7 +/- 235.8 mg.hr/L, respectively, which represents 41.3%
      and 43.0% of AUC0-12. The AUC0-12 for MPA measured 77.8 +/- 53.1 mg.hr/L and for
      MPAG 869.2 +/- 388.8 mg.hr/L. Seven patients (64%) exhibited a second peak at
      approximately 8.3 hours after the dose at a mean concentration (+/- standard
      deviation) of 10.3 +/- 7.6 mg/L. The Cmax or AUC of MPA does not correlate with
      overall Gastrointestinal Symptom Rating Scale scores or subscale scores, but the
      Cmax of MPAG correlates with indigestion subscale (P = 0.022), diarrhea (P =
      0.032), and overall scores (P = 0.028). The AUC of MPAG also correlates with acid
      reflux (P = 0.024) and indigestion (P = 0.032). DISCUSSION AND CONCLUSION: The
      pharmacokinetics of EC-MPS has a high variability in de novo kidney transplant
      patients of the Hispanic ethnicity, which was similar to other ethnic groups. The
      MPA exposure expressed by the AUC appears to be higher in Hispanic patients than
      those reported in other ethnic groups, which may be the result of various factors
      such as difference of the uridine diphosphate glucuronosyltransferase enzyme
      genotypes, but gastrointestinal side effects were acceptable and the Cmax or AUC
      of MPAG showed correlations with gastrointestinal symptoms.

PMID- 21099741
TI  - Barbiturate detection in oral fluid, plasma, and urine.
AB  - BACKGROUND: Although current abuse of barbiturates is low compared with other
      classes of abused drugs, their narrow margin of safety, risk of dependence, and
      abuse liability remain a health concern. Limited information is available on the
      disposition of barbiturates in different biologic matrices. OBJECTIVE: The
      authors conducted a clinical study of the disposition of barbiturates in oral
      fluid, plasma, and urine after single-dose administration to healthy subjects.
      METHODS: Three parallel groups of 15 subjects were administered a single oral
      dose of one barbiturate: butalbital (50 mg), Phenobarbital (30 mg), or sodium
      secobarbital (100 mg). Subjects remained at the clinic for two confinement
      periods; the first was -1 to 36 hours postdose and again at 48 to 52 hours. Oral
      fluid specimens were collected by bilateral collection (Intercept; one on each
      side of the mouth simultaneously). Blood specimens were obtained by venipuncture
      and urine specimens were collected through separate collection pools of varying
      periods. Oral fluid specimens were analyzed for barbiturates by liquid
      chromatography-tandem mass spectroscopy with a limit of quantitation of 8 ng/mL.
      Plasma and urine specimens were analyzed by gas chromatography-mass spectroscopy
      with a limit of quantitation of 100 ng/mL. RESULTS: Barbiturate side effects
      included dizziness, drowsiness, and somnolence. All effects resolved
      spontaneously without medical intervention. The three barbiturates were
      detectable in oral fluid and plasma within 15 to 60 minutes of administration and
      in the first urine pooled collection at 2 hours. Butalbital and Phenobarbital
      remained detectable in all specimens through 48 to 52 hours, whereas secobarbital
      was frequently negative in the last collection. Oral fluid to plasma ratios
      appeared stable over the 1- to 48-hour collection period. CONCLUSION: This study
      demonstrated that single, oral therapeutic doses of butalbital, Phenobarbital,
      and secobarbital were excreted in readily detectable concentrations in oral fluid
      over a period of approximately 2 days. Oral fluid patterns of appearance and
      elimination were similar to that observed for plasma and urine.

PMID- 21099742
TI  - Applications and biomonitoring issues of recombinant erythropoietins for doping
      control.
AB  - The biochemical actions and side effects of recombinant erythropoietins (rhEPOs),
      their analogs and mimetics, their misuse as doping agents, and the principal
      analytical strategies developed to identify them in athletes' biologic fluids are
      reviewed. Patients who experience a range of pathologies have benefited from the
      administration of rhEPOs to correct severe anemia. Currently, monitoring the
      biologic effect of rhEPO in patients under treatment is by measuring the
      hemoglobin concentration. However, it may be valuable to directly monitor the
      actual levels of the administered drug and determine a dose-dependent correlation
      with any clinical adverse effect observed. This may permit the adoption of a
      patient-specific administration regime. Currently, the method of detecting EPO
      approved for doping control is an isoelectric-focusing, double-blotting,
      chemiluminescence assay based on charge differences between isoforms of rhEPOs
      and endogenous EPO in urine. The advantages and limitations of this method are
      presented. A new approach using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis as a complementary tool to the established method is discussed.
      The application of matrix-assisted laser desorption/ionization mass spectrometry
      and liquid chromatography combined with tandem mass spectrometry for the direct
      detection of the rhEPO molecules may prove to be promising. Indirect evidence of
      rhEPO abuse by athletes is based on the analysis of blood parameters (hemoglobin
      hematocrit, reticulocytes, macrocytes, etc) and serum markers (concentration of
      EPO and serum transferrin receptors, etc). Enrichment of the screened parameters
      with gene or biochemical markers revealing altered erythropoiesis and adoption of
      longitudinal monitoring of athletes' hematologic and biochemical parameters could
      also be a complementary approach in the fight against doping.

PMID- 21099743
TI  - Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of
      venlafaxine.
AB  - This study examines the relationship between blood concentrations of venlafaxine
      and its active metabolite, O-desmethyl venlafaxine (ODV), and genetic variants of
      the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human subjects. Trough blood
      concentrations were measured at steady state in patients treated with venlafaxine
      extended release in a clinical practice setting. CYP2D6 and CYP2C19 genotypes
      were converted to activity scores based on known activity levels of the two
      alleles comprising a genotype. After adjusting for drug dose and gender effects,
      higher CYP2D6 and CYP2C19 activity scores were significantly associated with
      lower venlafaxine concentrations (P < 0.001 for each). Only CYP2D6 was associated
      with the concentration of ODV (P < 0.001), in which genotypes with more active
      alleles were associated with higher ODV concentrations. The sum of venlafaxine
      plus ODV concentration showed the same pattern as venlafaxine concentrations with
      CYP2D6 and CYP2C19 genotypes with higher activity scores being associated with a
      lower venlafaxine plus ODV concentration (2D6 P = 0.01; 2C19 P < 0.001). Because
      allelic variants in both CYP2D6 and CYP2C19 influence the total concentration of
      the active compounds venlafaxine and ODV, both CYP2D6 and CYP2C19 genotypes
      should be considered when using pharmacogenomic information for venlafaxine dose
      alterations.

PMID- 21099744
TI  - Impact of a preemptive strategy after 3 months of valganciclovir cytomegalovirus
      prophylaxis in kidney transplant recipients.
AB  - BACKGROUND: We assessed the impact of a preemptive strategy after discontinuation
      of antiviral prophylaxis in the prevention of late-onset cytomegalovirus (CMV)
      disease in a cohort of kidney transplant recipients. METHODS: Patients undergoing
      kidney transplantation at the University Hospital of Lausanne (CHUV) between
      November 2003 and November 2007 were included if they were donor or recipient
      (D/R) seropositive for CMV. All patients received 3 months of prophylaxis with
      valganciclovir, followed by monitoring of CMV DNAemia by polymerase chain
      reaction (PCR) every 15 days during 3 additional months. Valganciclovir was
      restarted if CMV PCR was more than or equal to 10,000 copies/mL. The primary
      endpoint of the study was the incidence of late-onset CMV disease. RESULTS.:
      Eighty-six kidney transplant recipients were included; 30 patients were D+/R- and
      56 patients were R+ for CMV. At 6 months posttransplant, CMV DNAemia had occurred
      in 31 of 86 (36%) patients: 13 of 30 (43%) in the D+/R- group and 18 of 56 (32%)
      in the R+ group (P = 0.35). In the D+/R- group, among the 13 patients with CMV
      DNAemia, 7 (54%) patients developed late-onset CMV disease, simultaneously to the
      first positive viral load (n = 5) or after detection of low-grade viremia (n =
      2). Only two patients received a preemptive treatment. In the R+ group, all
      positive PCR results were below the established cutoff. Thus, these 18 patients
      were not treated, and none of them developed late-onset CMV disease (R+ vs. D+/R
      : P < 0.001). CONCLUSIONS: Within the limitations of a noncontrolled study, our
      data indicate that a preemptive strategy after 3 months of valganciclovir
      prophylaxis for CMV is not useful in R+ kidney transplant recipients. In D+/R-
      patients, this approach should be further evaluated.

PMID- 21099757
TI  - Sports preparticipation examination to screen college athletes for Chlamydia
      trachomatis.
AB  - PURPOSE: This study assessed the prevalence of Chlamydia trachomatis in the
      college athlete and the benefit of using the sports preparticipation examination
      (PPE) as a screening opportunity. METHODS: Chlamydia teaching and screening was
      part of the sports PPE. The 439 athletes (220 men and 219 women) answered a
      questionnaire and provided urine specimens. Using positive test results as an
      indication of prevalence, the chlamydia prevalence rate was calculated by sex and
      race. Using the questionnaire responses, we determined the students'
      accessibility to health care and the percentage of sexually active students who
      were ever offered chlamydial screening. RESULTS: Thirteen of 439 athletes tested
      positive. One test was a false positive. The test positivity was 2.7%: 3.2% men
      and 2.2% women. In sexually active athletes, the test positivity rose to 3.8%:
      4.0% men and 3.7% women. African American athletes had a higher prevalence of
      9.1%: 8.9% in men and 9.5% in women, making them six times more likely to have
      chlamydia than Caucasian athletes (odds ratio = 6.43, 95% confidence interval =
      1.58-30.55). Number of partners, contraceptive type, symptoms, and prior history
      of chlamydia were not statistically different between groups. Over 75% of
      students saw their private physicians, yet of the sexually active students, only
      31% of women and 6.8% of men were ever offered chlamydial screening. CONCLUSIONS:
      The Centers for Disease Control and Prevention and the U.S. Preventive Services
      Task Force guidelines recommending annual chlamydial screening for all sexually
      active women younger than 26 yr are not being met in the community. Taking
      advantage of opportunities, including the mandated sports PPE, where sexually
      active men and women 25 yr and younger interface with the health care system to
      screen for C. trachomatis, is crucial to decreasing the continued rise of
      chlamydial infection.

PMID- 21099758
TI  - Energy cost of physical activities in persons with spinal cord injury--comment.

PMID- 21099759
TI  - Selected issues for the master athlete and the team physician: a consensus
      statement.

PMID- 21102166
TI  - Resolve.

PMID- 21102169
TI  - Standard for maintaining the competence of neonatal nurse practitioners. Position
      statement #3050.

PMID- 21102170
TI  - Palliative care of newborns and infants. Position Statement #3051.

PMID- 21102171
TI  - The importance of touch in the development of attachment.
AB  - Until recently the role of human touch in the social world of the developing
      infant has not been given special attention. Instead the focus, in part due to
      John Bowlby's Attachment Theory, has centered on the critical need for a child to
      develop a secure attachment to his caregiver. To be sure, this has provided a
      valuable contribution to understanding and promoting a child's well-being in his
      early years and beyond. Yet Bowlby's theory is limited in its discussion of the
      meaning of human touch and its role in development of attachment. As such, it now
      becomes more critical to delve into the factors that significantly foster
      development of attachment, specifically the concept of human touch. With
      recognition of the importance for a child to develop secure attachment to his
      caregiver, the essential function that human nurturing touch provides in
      facilitating that connection is explored.

PMID- 21102172
TI  - The comprehensive care rounds: facilitating multidisciplinary communication among
      caregivers of complex patients in the neonatal intensive care unit.
AB  - Care of the very sick infant can be complicated by extraneous factors that
      challenge the cohesiveness of the health care team. Chaos results from low levels
      of professional agreement and certainty about outcomes and manifests in stress
      and miscommunication among care providers. This milieu is fertile ground for
      errors of commission and omission. Effective communication and collaboration are
      recognized as essential for reducing medical errors in such stressful
      environments. This article describes a multidisciplinary conference, the
      Comprehensive Care Rounds, at a neonatal intensive care unit of a Magnet
      recognized midwestern pediatric hospital. The Comprehensive Care Round provides a
      forum for open communication among team members and builds on the hospital's
      efforts at systems approach to developing a culture of safety and quality.

PMID- 21102173
TI  - A case of massive meconium peritonitis in utero successfully managed by planned
      cardiopulmonary resuscitation of the newborn.
AB  - We report a case of emergent massive meconium peritonitis due to intrauterine
      volvulus without malrotation. Fetal ascites was detected on a regular
      ultrasonographic examination, and fetal distress was found on cardiotocographic
      monitoring. The mother had noticed a slight decrease in fetal movements over the
      preceding 24 hours. Prenatal magnetic resonance imaging allowed us to distinguish
      the meconium from fetal peritoneal fluid and to evaluate the degree of
      compression of the fetal thoracic cavity. The infant was delivered by emergency
      cesarean section and demonstrated tense abdominal ascites with edema at birth.
      She required cardiopulmonary resuscitation and immediate paracentesis.

PMID- 21102174
TI  - Responding to traumatic birth: subgaleal hemorrhage, assessment, and management
      during transport.
AB  - Subgaleal hemorrhage is an uncommon but often fatal complication of a traumatic
      birth. Careful assessment and monitoring of the infant following birth are
      necessary to ensure prompt intervention, referral, and improved outcomes.
      Additional care, planning, and communication are especially important in the
      transport environment.

PMID- 21102175
TI  - Parental decision making regarding treatment of hypoplastic left heart syndrome.
AB  - Parents of children diagnosed with a complex congenital heart anomaly such as
      hypoplastic left heart syndrome (HLHS) are faced with the challenge of choosing
      the best treatment option for their children. Parents must decide among options
      of compassionate care, palliative reconstructive surgery, or neonatal cardiac
      transplantation, and additionally with antenatal diagnosis must decide regarding
      continuation of pregnancy. With improved survival rates yet persistent
      morbidities following the Norwood surgical approach for HLHS, controversy remains
      whether parents should be counseled on all treatment options as evidenced by
      research that articulates the varied opinions of health care providers. The
      parents' perspective is less well researched. In this study, interview data from
      parents who chose the Norwood-Sano surgical option were analyzed to provide
      insight into the various treatment options they were given following diagnosis of
      HLHS in their children and how they came to choose the surgical palliation
      option.

PMID- 21102177
TI  - Modeling clinical applications in intensive care settings for nursing
      orientation.
AB  - The nursing shortage continues to influence the health care industry, as
      hospitals and other agencies invest resources into hiring and training registered
      nurses to care for patients. Intensive care nurseries and other specialty units
      have utilized new graduate registered nurses to reach desired staffing ratios.
      However, traditional nursing school programs do not routinely prepare graduates
      for positions in such areas. Orientation programs, especially in intensive care
      settings, will need structured orientation plans to maximize the opportunities
      for novice nurses to acquire complex skills and develop critical thinking
      abilities specific to the patient population. This NICU is an 82-bed, regional
      level III unit that historically hires new graduate nurses. The purpose of this
      project was to provide a structured orientation program that utilized computer
      based instruction, hands-on learning experiences, and adult learning principles
      to guide new nurses in the development of their professional practice.

PMID- 21102178
TI  - Managing desaturations in preterm infants.

PMID- 21102179
TI  - Implementation of the American Academy of Pediatrics recommendations to reduce
      sudden infant death syndrome risk in neonatal intensive care units: An evaluation
      of nursing knowledge and practice.
AB  - There is a direct relationship between nonsupine sleeping and sudden infant death
      syndrome (SIDS). Premature infants are at greater risk for SIDS and are often
      cared for in nonsupine positions during the course of hospitalization. Healthy
      premature infants should be placed supine for sleep before discharge from the
      neonatal intensive care unit (NICU), and parents receive specific instruction
      about infant sleep position and other risk factors for SIDS. Most published
      literature addressing nursing practices for SIDS reduction reflects practices
      with the healthy newborn population. PURPOSE: To examine and describe NICU
      nurses' knowledge of SIDS risk-reduction measures, modeling of safe infant sleep
      interventions prior to discharge, and inclusion of SIDS risk reduction in parent
      education. SUBJECTS: Convenience sample of nurses practicing in level II and III
      NICUs located in 2 Middle Atlantic States. DESIGN AND METHODS: A prospective
      survey design was used for the study. The 14-item questionnaire was developed by
      a team of neonatal clinical experts and distributed via site coordinators to
      nurses in 19 NICUs. PRINCIPAL RESULTS: A total of 1080 surveys were distributed
      and 430 (40%) NICU nurses completed the survey. The majority of nurses (85%)
      identified the American Academy of Pediatrics SIDS risk-reduction strategies for
      safe sleep. The investigators found that age, years of nursing and neonatal
      nursing experience, and educational preparation did not significantly contribute
      to the practice of "supine-only" position for sleep for infants in NICUs. The
      study revealed that nurses frequently position healthy preterm infants supine for
      sleep when weaned to an open crib (50%). Others wait one to a few days before
      discharge (15%) and some never position supine for sleep (6%). Stuffed toys are
      removed from cribs 90.5% of the time. For term infants without major medical
      complications, 45.5% of surveyed nurses continued to use positioning aids/rolls
      in infants' cribs. The most common reasons nurses cited to position preterm
      infants side-lying or prone in a crib were fear of aspiration (29%), infant
      comfort (28%), and infant safety (20%). NICU nurses educated parents about SIDS
      and reduction strategies, using various media. At discharge, 73% of the nurses
      verbally communicated with parents, 53% provided printed literature, and 14% used
      audiovisual aids with parents. CONCLUSIONS: NICU nurses are in influential
      positions to educate parents and model SIDS risk-reduction strategies. This study
      supports other published research that points to inconsistencies in nursing
      practice regarding implementation of methods to reduce the risk of SIDS.

PMID- 21102180
TI  - Decreasing noise level in our NICU: The impact of a noise awareness educational
      program.
AB  - BACKGROUND: The literature demonstrates that most NICUs exceed the standard
      recommendations for noise levels and that high noise levels have a negative
      impact on patients and staff. OBJECTIVE: The objective of this research was to
      measure baseline noise level in an NICU, compare it to recommendations of
      international bodies, and evaluate the impact of a noise awareness educational
      program (NAEP) as a strategy to decrease it. DESIGN/METHODS: Means of hourly
      average noise levels in decibels (dB) were compared with the recommendations and
      pre- and postintervention (P = .05). RESULTS: Mean noise-level preintervention
      was significantly higher than recommended (58.15 vs 45 dB; P < 0.001). The
      participation rate in NAEP was excellent and most participants thought that the
      content was relevant and would change their practice. Overall, at first glance,
      the impact of the NAEP was not as expected: the noise levels increased
      nonsignificantly postintervention (58.15 vs 58.46 dB; P < .181). However, a
      significant increase in activity level (number of nurses and patient) was thought
      to be responsible for the lack of significance postintervention. After
      controlling for these variables, it was demonstrated that the noise level did
      significantly decrease postintervention (6.33 vs 5.42 dB per RN & 4.68 vs 4.08 dB
      per patient, P < .000). CONCLUSION: Although the efficacy of the program was
      significantly limited by an increase in general activity, it raised staff
      awareness and had important effects reflected by the significant decrease in mean
      noise level after standardization and the participant's comments.

PMID- 21102181
TI  - Research into readings past.

PMID- 21102183
TI  - Cross-limb vascular shunting for major limb replantation.

PMID- 21102190
TI  - From creatine kinase-MB to troponin: do we really need to differentiate between
      myocardial injury and infarction?

PMID- 21102191
TI  - Reticulocyte hemoglobin content in critically ill patients.

PMID- 21102192
TI  - On memory, general anesthesia, and sleep.

PMID- 21102195
TI  - The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in
      distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with
      papillary features.
AB  - PAX-2, a homeogene expressed during kidney development, has been studied as a
      marker of renal origin in both primary and metastatic clear cell renal cell
      carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker
      (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24
      papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a
      variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%)
      were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10
      (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous
      carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary
      thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%)
      uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas,
      1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%)
      choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features,
      and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of
      PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There
      is significant overlap between the expressions of these markers in PRCC and
      NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC
      and may prove useful in the initial work up of metastases of unknown primary. PAX
      2 and RCCma immunohistochemistry should be interpreted with caution in papillary
      neoplasms, with particular attention to the possibility of ovarian and uterine
      papillary serous carcinomas, which can express both PAX-2 and RCCma.

PMID- 21102196
TI  - Infectious keratitis treated with corneal crosslinking.
AB  - PURPOSE: To describe 7 eyes with severe infectious keratitis treated using
      collagen crosslinking (CXL) with riboflavin. MATERIALS AND METHODS: Seven eyes of
      6 patients with severe infectious keratitis were treated with corneal
      crosslinking. Three patients were contact lens users. Symptom duration before CXL
      ranged between 0 and 7 days. Corneal melting was present in all cases.
      Photodocumentation of the keratitis was carried out and repeated at follow-up.
      All but 1 patient received topical antibiotic treatment in addition to the CXL
      treatment. CXL was conducted according to the standardized protocol for
      keratoconus. RESULTS: In all but 1 eye, patients experienced improvement in
      symptoms within 24 hours. Two patients reported no symptoms whatsoever at this
      time. Corneal melting was arrested and complete epithelialization was achieved in
      all cases. In the 2 eyes with hypopyon, this regressed completely within 2 days
      after the CXL. Follow-up ranged between 1 and 6 months. DISCUSSION: Our
      experience based on the above and other cases suggest that CXL could be an
      effective tool in battling difficult cases of infectious keratitis. This
      treatment could present many advantages but will need further investigation.

PMID- 21102197
TI  - Advanced containment methods for Legg-Calve-Perthes disease: results of triple
      pelvic osteotomy.
AB  - BACKGROUND: Although surgical containment has become a mainstay for the treatment
      of Legg-Calve-Perthes (LCP) disease; traditional operations (varus osteotomy of
      femur, Salter osteotomy) have certain limitations, sometimes resulting in a
      prolonged limp or inadequate containment. This paper presents the surgical method
      and results of triple pelvic osteotomy for containment treatment of LCP disease.
      METHODS: This retrospective review of 39 children (40 hips; age 5 to 13 y) with
      LCP disease treated with triple pelvic osteotomy (1995 to 2005) included
      preoperative lateral pillar assessment and other measurements. Final follow-up
      films (minimum 3 y, range 3 to 9 y) were assessed using the modified Stulberg
      classification. Clinical follow-up evaluation assessed limp, limb-length
      inequality, range of motion, and activity level. RESULTS: Twenty-one (53%) hips
      were graded as lateral pillar B and 19 (48%) were lateral pillar C. Four patients
      required further treatment before the final follow-up. At final follow-up, 42%
      had a good outcome (Stulberg I/II), 47% had a fair outcome (Stulberg III), and
      11% had a poor outcome. Thus, 89% of patients had satisfactory (good or fair)
      results. There was a significant difference in outcome based on the preoperative
      lateral pillar, with B hips more likely to have a good outcome (65%) compared
      with lateral pillar C hips (12.5%) (P=0.002). There were no lateral pillar B
      patients with a poor outcome. Seventeen percent of the lateral pillar C patients
      more than or equal to age 8 had a poor outcome compared with 50% being more than
      age 8 with a poor outcome. Four patients (3 lateral pillar C, 1 lateral pillar B)
      required further surgery. CONCLUSIONS: Triple pelvic osteotomy resulted in
      maintenance of head shape in lateral pillar B patients of all ages and in younger
      lateral pillar C patients. Lateral pillar C patients over age 8 were more
      difficult to treat, however, we still advise containment for these cases because
      methods are now available to deal with containment failure. Triple pelvic
      osteotomy is an effective treatment method for LCP patients with lateral pillar B
      disease and younger patients with lateral pillar C disease. This method provides
      effective containment, which allows prolonged remodeling while avoiding the
      limitations of femoral varus osteotomy (limp, short limb) and Salter osteotomy
      (incomplete containment). LEVEL OF EVIDENCE: Level IV.

PMID- 21102199
TI  - Avascular necrosis most common indication for hip arthroplasty in patients with
      slipped capital femoral epiphysis.
AB  - BACKGROUND: Recently, much attention has been focused on the prevention of
      arthritis after slipped capital femoral epiphysis (SCFE). Little, however, is
      published on which subset of SCFE patients eventually require hip replacement,
      how soon arthroplasty is required, and the long-term outcomes after arthroplasty.
      METHODS: A hip registry database at a tertiary referral center was searched for
      all primary hip arthroplasties in patients with a confirmed childhood diagnosis
      of SCFE. RESULTS: From 1954-2007, 38 hips in 33 patients underwent arthroplasty,
      including total hip arthroplasty (28), hip resurfacing (8), and hemiarthroplasty
      (2) for the diagnosis of SCFE. During this time period, over 33,000 primary total
      hip arthroplasties were carried out at our center. Underlying diagnoses included
      avascular necrosis or chondrolysis in 25 hips and degenerative changes and/or
      impingement in 13 hips. The slip severity in 20 cases was severe, 4 moderate, 7
      mild, and 7 hips had unknown slip severity. Half of the slips (7/14) in the
      degenerative group were mild or moderate. Fourteen (70%) of the 20 severe slips
      and 10 (71%) of the 14 acute or acute-on-chronic slips presented for arthroplasty
      with the diagnosis of avascular necrosis. Avascular necrosis was associated with
      a severe slip (P=0.03) and an acute or acute-on-chronic presentation (P=0.008).
      With the exception of 2 mild slips treated nonoperatively, all slips underwent
      either pin fixation (27) or primary osteotomy (9). Mean time from slip to
      arthroplasty was 7.4 years in patients with AVN or chondrolysis, compared with
      23.6 years in patients with degenerative change (P<0.0002). Mean age at
      arthroplasty was 20 years in the AVN or chondrolysis group compared with 38 years
      in the degenerative group (P<0.0001). Sixteen hips required revision arthroplasty
      at a mean of 11.6 years postoperatively, most commonly for component loosening
      and/or polyethylene wear. Kaplan Meier 5-year survival free from revision for all
      causes was 87% overall and 95% in the total hip arthroplasty subset. CONCLUSIONS:
      The majority of hip arthroplasties in patients with slipped capital femoral
      epiphysis were carried out for the indication of avascular necrosis rather than
      degenerative changes related to femoroacetabular impingement. We found a
      moderately high revision rate in SCFE patients undergoing total hip arthroplasty
      or other joint replacement. LEVEL OF EVIDENCE: IV, case series.

PMID- 21102198
TI  - Sequelae of Perthes disease: treatment with surgical hip dislocation and relative
      femoral neck lengthening.
AB  - BACKGROUND: Sequelae of Perthes disease commonly manifests as complex hip
      pathomorphology including coxa magna, coxa brevis, and acetabular dysplasia.
      These abnormalities contribute to femoroacetabular impingement and early
      osteoarthritis. This report describes our experience with correction of the
      proximal femoral deformity associated with Perthes disease through surgical
      dislocation, osteochondroplasty (SDO), trochanteric advancement, and treatment of
      intraarticular chondrolabral injury. METHODS: Between January 2003 and January
      2009, 14 patients with Perthes disease (4 female and 10 male patients) with an
      average age of 19.6 years (range 14 to 28 y) were treated with SDO and
      trochanteric advancement. One patient had a subsequent staged periacetabular
      osteotomy to improve acetabular coverage. Patient histories, physical
      examinations, operative findings, and preoperative and postoperative radiographs
      were evaluated. RESULTS: Operative findings showed 6 acetabular cartilage
      lesions, 6 labral lesions, and 4 femoral osteochondritis dissecans (OCD) lesions
      treated with autografts. The mean of center-trochanteric distance improved from 
      20 mm to -1 mm. Approximately 4 of 14 hips deteriorated to Tonnis grade 1 and 1
      of 14 hips deteriorated 2 Tonnis grades. The Harris hip scores improved from an
      average of 62 preoperatively (range 51 to 72) to 95 postoperatively (range 93 to
      97) with OCD lesions versus 71 (range 65 to 76) to 88.6 (range 63 to 100) in the
      hips without OCD lesions. There was no statistically significant difference in
      the age, preoperative or postoperative HHSs between the OCD and non-OCD groups.
      The mean follow-up was 45 months. There were no major perioperative
      complications, and all the patients in both the groups have their native hip to
      date. CONCLUSIONS: The typical adult sequelae of Perthes disease predispose the
      hip to the development of chondrolabral injury and poor clinical function.
      Treatment with SDO and trochanteric advancement reduces impingement, improves hip
      biomechanics, and allows the treatment of intraarticular pathology. This approach
      is associated with clinical improvement without major perioperative
      complications. In addition, we have found a high rate of OCD lesions of the
      femoral head in Perthes hips undergoing surgical dislocation. Osteochondral
      autograft transfer from the resected femoral head-neck junction been found in the
      4 patients treated thus far to be safe and effective with comparable clinical and
      radiographic outcomes to those hips without OCD lesions. LEVEL OF EVIDENCE: Level
      IV (Case series).

PMID- 21102200
TI  - Developmental dysplasia of the hip in twins: the importance of mechanical factors
      in the etiology of DDH.
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is a disease of
      multifactorial etiology. Genetic and intrauterine mechanical factors influence
      the development of the hip joint and the incidence of DDH. Breech position is a
      risk factor for DDH. The aim of this study is to analyze whether in twins, the
      intrauterine mechanical factors, such as a breech position, limitation of fetal
      mobility, limitation of hip abduction, and increase the incidence of DDH may,
      therefore, be considered as risk factors. METHODS: A pair of twins with either
      breech or cephalic presentation, and no family history of DDH or any other
      sicknesses were included in this study. During a 6-year period between 2002 and
      2007, data were collected on 105 consecutively born twins (210 children with 420
      hips) of whom 48 were a cephalic breech, 35 were a cephalic-cephalic, and 22 were
      a breech-breech presentation. The presentation was defined by regular prenatal
      ultrasounds and the obstetric records at birth. The average gestational age was
      36.7 weeks and average weight at birth was 2290 g. Control group 1 consisted of
      274 single gestation children, with a cephalic presentation at birth. The average
      gestational age was 39.1 weeks and average weight at birth was 3200 g. Control
      group 2 consisted of 48 single gestation children, with a breech presentation at
      birth. The average gestational age was 36.8 weeks and average weight at birth was
      2870 g. Ultrasonography of the hips was done according to the Graf technique.
      Statistical analysis was done using a chi2 test. RESULTS: The chi2 test was used
      and it showed no significant association between the presence or absence of
      pathologic hip types in the twins group and in the 2 control groups. A higher
      incidence of DDH (3.4%) was present in groups 1 and 2. CONCLUSIONS: This
      comparison of a large series of twins with matched controls shows that there is
      no increased incidence of DDH in twins when compared with single birth infants
      with no family history of DDH. This study supports the idea that breech
      presentation in twins is not a risk factor, when knees are flexed. LEVEL OF
      EVIDENCE: Retrospective study. Level 2 study.

PMID- 21102201
TI  - Complications of talus fractures in children.
AB  - BACKGROUND: Pediatric talus fractures are rare with variable rates of
      posttraumatic complications reported in the literature. The purpose of this
      retrospective study was to evaluate posttraumatic complications in children after
      talus fracture and report injury characteristics. METHODS: This study included 29
      children with talus fractures sustained between 1999 and 2008 at an average age
      of 13.5 years (range, 1.2-17.8). Patient records and radiographs were reviewed to
      determine the mechanism of injury, fracture type, associated injuries, and
      treatment. Posttraumatic complications assessed were avascular necrosis,
      arthrosis, nonunion or delayed union, neurapraxia, infection or wound-healing
      problems, and the need for further unanticipated surgery. Clinical follow-up
      averaged 24 months (range, 6 mo-5 y). RESULTS: Twenty-nine children sustained a
      major fracture of the talar body, neck, or head. Avascular necrosis occurred in 2
      patients (7%), arthrosis in 5 (17%), delayed union in 1 (3%), neurapraxia in 2
      (7%), infection in 0, and the need for further surgery in 3 (10%). Both high
      energy mechanism and fracture displacement corresponded to a greater number of
      posttraumatic complications. The number and severity of talus fractures increased
      in older children. CONCLUSIONS: In this case series, posttraumatic complications
      after pediatric talus fractures occurred more frequently after a high-energy
      mechanism of injury or a displaced fracture. Talus fractures occurred more
      commonly and with more severity in older children. LEVEL OF EVIDENCE: Level IV.
      Retrospective case series.

PMID- 21102202
TI  - The effects of surgical delay on the outcome of pediatric supracondylar humeral
      fractures.
AB  - BACKGROUND: Occasionally, the treatment of a pediatric supracondylar humeral
      fracture is delayed owing to lack of an available treating physician,
      necessitating transfer of the child, or delay in availability of an operating
      room. The purpose of this study is to prospectively evaluate whether delayed
      pinning of these fractures affects the outcome or number of complications.
      METHODS: We reviewed information that was prospectively collected on 145
      pediatric supracondylar humeral fractures that were treated by closed reduction
      and percutaneous pinning, with a minimum follow-up of 8 weeks. To determine the
      effect of delayed treatment, we compared a group of fractures that was treated
      within the first 21 hours after their presentation to our urgent care center
      (Group A) with a group that was treated after more than 21 hours (Group B). We
      compared the following variables: need for open reduction, length of surgery,
      length of hospitalization, the presence of neurologic complications, vascular
      complications including compartment syndrome, pin tract infection, loss of
      fixation, final carrying angle, range of motion, and outcome. RESULTS: Overall,
      the mean time from presentation to surgery for both groups was 52 hours. This
      interval was greater for Gartland type II fractures (65 h) than for Gartland type
      III fractures (19 h) (P=0.00001). There was no need for an open reduction in
      either group. There were no significant differences between the groups regarding
      iatrogenic nerve injuries, vascular complications, compartment syndromes,
      surgical time, final carrying angle, range of motion, and outcome. CONCLUSIONS:
      The results of this prospective study found that a delay in pinning closed
      supracondylar humeral fractures in children did not lead to a higher incidence of
      open reduction or a greater number of complications. Although the urgency of
      treating any child with a supracondylar fracture should be individualized, our
      study suggests that most of these injuries can be managed safely in a delayed
      fashion without compromising the clinical outcome. We recommend careful
      monitoring of any patient with type 3 injury whose treatment is delayed. LEVEL OF
      EVIDENCE: II.

PMID- 21102203
TI  - Pin size influences sagittal alignment in percutaneously pinned pediatric
      supracondylar humerus fractures.
AB  - BACKGROUND: No study examining pin constructs has adequately addressed pin size
      and its role in fracture fixation. Our goal was to review our experience with
      Wilkins-modified Gartland type-III pediatric supracondylar humerus fractures
      treated with closed reduction and percutaneous pinning to evaluate the effects of
      pin size within 2 different pin constructs on maintenance of reduction and on the
      risk of surgical complications. METHODS: We retrospectively reviewed the medical
      records of pediatric patients with Wilkins-modified Gartland type-III
      supracondylar humerus fractures that were closed reduced and percutaneously
      pinned at our institution from March 1999 through December 2008. We grouped those
      159 patients by fracture stabilization method (lateral-entry-pin or crossed-pin
      constructs), by pin size ratio (ie, ratio of pin diameter to the humeral midshaft
      cortical thickness: small <=0.9; large >0.9), and then by 4 combinations of pin
      construct and pin size ratio. For each group, we evaluated radiographs for
      immediate postoperative reduction (coronal and sagittal alignment), maintenance
      of reduction at last follow-up, and the number of surgical complications. We used
      the Student t test, chi2 test, Mann-Whitney U test, and Wilcoxon Signed Rank test
      to examine for significance, which was set at P<0.05. RESULTS: Although we found
      no significant differences between the groups immediately after surgery, final
      follow-up sagittal alignment was significantly more likely to be maintained in
      the large pin size ratio group than in the small pin size ratio group. For 2
      types of surgical complications, infection and nerve palsy, we found no
      statistically significant differences in these complications between the pin
      construct or pin size ratio groups. CONCLUSIONS: Large pin sizes improved
      radiographic sagittal alignment at final follow-up without an increased rate of
      infection or ulnar nerve palsy. LEVEL OF EVIDENCE: Level III Therapeutic Study.

PMID- 21102204
TI  - Medial and lateral pin versus lateral-entry pin fixation for Type 3 supracondylar
      fractures in children: a prospective, surgeon-randomized study.
AB  - BACKGROUND: The purpose of this study is to compare the efficacy of medial and
      lateral (crossed pin) and lateral-entry pin techniques for Gartland Type 3
      supracondylar humerus fractures in children. METHODS: Six pediatric orthopaedists
      were divided into the 2 treatment groups (medial and lateral pins or lateral only
      pins) based on pre-study pinning technique preferences. Patients were randomized
      into 1 of the 2 pinning technique treatment groups based on which attending was
      on call at the time of patient presentation. One hundred and four patients met
      inclusion criteria. Forty-seven patients underwent lateral-entry pinning and 57
      underwent crossed pinning. The 2 groups were similar with respect to age, sex,
      preoperative neurovascular injury, direction of fracture displacement, and timing
      of surgery. Outcome parameters measured included radiographic maintenance of
      reduction, iatrogenic neurovascular complications, and rate of infection. All
      radiographic measurements, and interobserver reliability, were determined by a 3
      physician panel. RESULTS: The results of the interobserver reliability data
      showed a strong correlation and this data allowed 95% confidence that a change in
      Baumann's angle of more than 6 degrees and humerocapitellar angle of more than 10
      degrees was significant. The lateral-entry patients experienced a median absolute
      change of Baumann's angle of 3.7 degrees with 12 patients having greater than 6
      degrees loss of reduction; whereas those in the medial and lateral-pin group saw
      a median change of 2.9 degrees with 10 patients having greater than 6 degrees
      loss of reduction. In terms of the humerocapitellar angle, the lateral-entry
      patients experienced a median absolute change of 4.8 degrees with 11 patients
      having greater than 10 degrees loss of reduction; whereas those in the medial and
      lateral-pin groups saw a median change of 5.1 degrees with 17 patients having
      greater than 10 degrees loss of reduction. There was no significant difference in
      infection rate between the 2 groups but 2 cases of iatrogenic neurovascular
      injury occurred in patients who had a medial pin placed. CONCLUSIONS: We found no
      statistical difference in the radiographic outcomes between lateral-entry and
      medial and lateral-pin techniques for the management of Type 3 supracondylar
      fractures in children when evaluated in this prospective and surgeon-randomized
      trial, but 2 cases of iatrogenic injury to the ulnar nerve occurred with medially
      placed pins. LEVEL OF EVIDENCE: Level 2.

PMID- 21102205
TI  - Assessment of muscular performance in teenagers after a lower extremity fracture.
AB  - BACKGROUND: Deleterious effects of lower limb immobilization in adults have been
      well described and suggest that altered muscle strength was not fully recoverable
      after rehabilitation. In this study, we hypothesized that the same significant
      differences in strength and power performances between the injured and noninjured
      leg are foreseeable 18 months after a lower limb fracture in teenagers, and
      between injured adolescents and healthy controls. METHODS: The effects of cast
      immobilization on the strength and power performance were evaluated 18 months
      after a lower limb fracture in 39 injured teenagers who were paired with healthy
      controls. Strength and power performance were assessed during a single-leg
      vertical jump test using a force platform. RESULTS: At 18 months, strength
      performance in injured teenagers was similar in both lower limbs. A significant
      difference was found between injured and noninjured legs for maximal muscular
      power measurement. However, the limb symmetry index was superior to 85% for
      maximal muscular power, which should be considered as normal. Limb asymmetries
      greater than 15% for muscular strength and power were more frequent in injured
      teenagers than in noninjured children and adolescents, but the difference was
      statistically significant only for the mean muscle power (P=0.0003). CONCLUSIONS:
      These findings show that the recovery of muscular strength and power is
      foreseeable after a lower limb fracture in the pediatric population, even if a
      greater percentage of injured teenagers was found to have limb asymmetries
      greater than 15% for mean muscular power 18 months after trauma compared with the
      healthy controls. LEVEL OF EVIDENCE: Level III, case-control study.

PMID- 21102206
TI  - Immediate spica casting of pediatric femoral fractures in the operating room
      versus the emergency department: comparison of reduction, complications, and
      hospital charges.
AB  - BACKGROUND: Immediate spica casting for pediatric femur fractures is well
      described as a standard treatment in the literature. The purpose of this study is
      to evaluate the application of a spica cast in the emergency department (ED)
      versus the operating room (OR) with regard to quality of reduction,
      complications, and hospital charges at an academic institution. METHODS: An
      institutional review board-approved retrospective review identified 100 children
      aged 6 months to 5 years between January 2003 and October 2008 with an isolated
      femur fracture treated with a hip spica cast. Patients were compared based on the
      setting of spica cast application. RESULTS: There were 79 patients in the ED
      cohort and 21 patients in the OR cohort. There were no significant differences in
      age, weight, sex, fracture pattern, prereduction shortening, injury mechanism,
      duration of spica treatment, time to heal, or length of follow-up between
      cohorts. There were no significant differences in the rate of loss of reduction
      requiring revision casting or operative treatment (6.3% vs. 4.8%), the need for
      cast wedging (8.9% vs. 14.3%), or minor skin breakdown (12.7% vs. 14.3%). There
      were no sedation or anesthetic complications in either group. There were no
      significant differences in the quality of reduction or the rate of complications
      between the 2 groups. Spica casting in the OR delayed the time from presentation
      to cast placement as compared with the ED cohort (11.5 h vs. 3.8 h, P<0.0001) and
      lengthened the hospital stay (30.5 h vs. 16.9 h, P=0.0002). The average hospital
      charges of spica cast application in the OR was 3 times higher than the cost of
      casting in the ED ($15,983 vs. $5150, P<0.0001). CONCLUSIONS: Immediate spica
      casting in the ED and OR provide similar results in terms of reduction and
      complications. With the significantly higher hospital charges for spica casting
      in the OR, alternative settings should be considered. LEVEL OF EVIDENCE: III-
      Retrospective comparative study.

PMID- 21102207
TI  - Effects of a pediatric physeal slide-traction plate on fracture healing: an
      experimental study in a goat model.
AB  - BACKGROUND: It has been an intractable issue for the orthopaedic surgeons to
      treat pediatric epiphyseal injury and surrounding bone fracture using Kirschner
      wires and screws, etc. Earlier research has indicated that pediatric physeal
      slide-traction plate (PPSP) can fix bone fracture without restricting growth.
      However, it is not clear whether this material can be clinically used to treat
      pediatric epiphyseal injury and surrounding bone fracture. METHODS: The PPSP and
      standard plate (SP) were designed to configure to the femoral condyle. Twelve
      premature female goats were enrolled in this study. Fracture models were
      successfully established on goats, on which the right femurs were fixed with SP,
      and the left femurs were fixed with PPSP. Radiographic analysis and biomechanical
      tests were done at 4 and 8 weeks after surgery. RESULTS: The callus gray density
      increased with time going on in each group, at the same postoperational time
      point, the PPSP group was higher than that of the SP group. The difference
      between PPSP group and SP group was statistically significant at the same stage
      (P<0.01). The biomechanical tests showed that the PPSP group was stronger than
      the SP group in anticompression, antibending, and antitorsion at the same stage
      (P<0.05). In addition, it was shown through the radiographic analysis that PPSP
      extended accordingly as the epiphyseal plate grows, and the epiphyseal morphology
      was considered normal all the time. However, epiphyseal premature closure and
      angular deformity were observed in the samples of the SP group. CONCLUSIONS: PPSP
      contributed greatly to healing of bone fracture with increased callus density and
      callus strength in the early stage, and did not restrict the growth of the
      epiphyseal plate. It may be clinically applied in the treatment of pediatric
      epiphyseal injury and surrounding bone fracture in the future. LEVEL OF EVIDENCE:
      Therapeutic level II.

PMID- 21102208
TI  - Proximal femoral osteotomy in neurologic pediatric hips using the locking
      compression plate.
AB  - BACKGROUND: Proximal femoral osteotomy (PFO) is a widely performed reconstructive
      surgery in pediatric patients with diagnosis of neurologic abnormalities. Many
      implants have been used for the fixation of these osteotomies. These devices have
      been evolved to provide stable fixation. A novel fixation system, the proximal
      femoral locking compression plate (LCP), which has a low lateral profile system,
      has been developed to address the problem of loosening in the osteoporotic bone,
      and to reach a more precise angular reduction and fixation stability through the
      use of locking screws. In this study, we report the surgical technique and
      results of PFO in children with a neurologic diagnosis. METHODS: Fifty-two
      children with a primary neurologic diagnosis had a femoral osteotomy with the LCP
      device. Clinical records and radiographs, neck-shaft angle (NSA), acetabular
      slope, the Reimer migration percentage, and healing of the osteotomy site were
      studied. Among the 70 operated hips, 59 operated hips had a follow-up superior to
      1 year and were included in this study. RESULTS: Among the 59 operated hips, 25
      operated hips presented with subluxations. NSA improved from 145 degrees (130
      degrees to 165 degrees) to 120 degrees (110 degrees to 125 degrees) and to 125
      degrees (115 degrees to 130 degrees) on last follow-up. The Reimer migration
      percentage improved from 60% (35% to 90%) to 25% (15% to 35%). Ten operated hips
      presented with dislocations. Their NSA improved from 150 degrees (145 degrees to
      170 degrees) to 122 degrees (115 degrees to 125 degrees) and to 125 degrees (118
      degrees to 130 degrees) at last follow-up. The stability of the operative
      reduction was maintained and full range of motion was preserved. Five operated
      hips presented with dysplastic hips with NSA>130 degrees without associated
      subluxation, 6 operated hips presented with windswept deformities, 10 operated
      hips presented with excessive femoral anteversion, and 3 operated hips presented
      with pseudarthrosis after earlier PFO were also treated and neither presented
      angular loosening at last follow-up. No major complications were observed.
      CONCLUSIONS: The LCP system may be used for a wide range of indications if
      precise preoperative planning was achieved. Rigid primary fixation allows early
      mobilization and weight bearing in ambulant patient. LEVEL OF EVIDENCE LEVEL IV:
      Therapeutic study investigating the results of a treatment studying a case
      series.

PMID- 21102209
TI  - Management of severe crouch gait in children and adolescents with cerebral palsy.
AB  - BACKGROUND: Crouch gait in cerebral palsy is associated with spasticity and
      contracture of the hamstrings and weakness of the extensors of the hip and knee
      and ankle plantar flexors. Different treatment options have been described in the
      literature to deal with this difficult problem. We devised a different protocol
      of treatment aimed at correction of the flexion deformity of the knee, weakening
      of the hamstrings, and augmenting the power of the knee and hip extension, which
      we used on 17 children with severe crouch. METHODS: This surgery, performed in 2
      stages, entailed shortening of the femur, plication of the patellar tendon,
      transfer of the semitendinous to the back of the femur, and fractional
      lengthening of the other hamstrings. The degree of fixed deformity, the popliteal
      angle, quadriceps power, range of knee motion, ambulatory status and the
      efficiency of gait, and the position of the patella were evaluated before surgery
      and again after a minimum 2-year follow-up. RESULTS: The gait improved and the
      power of the quadriceps and the range of knee motion increased. The flexion
      deformity and popliteal angle decreased significantly. Patella alta was corrected
      and all fragmentation of the tibial tuberosity and fractures of the patella
      healed. The Functional Mobility Scores and the ambulatory capacity increased in
      all the children. There was no evidence of damage to the sciatic nerve in any
      patient. CONCLUSIONS: The method of treatment of severe crouch gait outlined in
      this study seems to be an effective and safe method of dealing with this
      difficult problem. STUDY DESIGN:  LEVEL OF EVIDENCE: IV.

PMID- 21102210
TI  - Effectiveness of an anesthetic continuous-infusion device in children with
      cerebral palsy undergoing orthopaedic surgery.
AB  - BACKGROUND: Effective postoperative pain management is a vital component of
      orthopaedic surgical care in the pediatric population. In children with cognitive
      impairments pain management can be difficult, making these children vulnerable to
      ineffectively managed postoperative pain. This prospective, randomised study
      evaluated the use of a local anesthetic continuous infusion device (pain pump) to
      manage postoperative pain in children with cerebral palsy (CP) undergoing lower
      extremity orthopaedic surgical procedures. METHODS: Children with a diagnosis of
      CP who were undergoing select orthopaedic outpatient procedures were enrolled in
      this study. Postoperatively, patients were randomised to receive either a pain
      pump in addition to oral analgesics or oral analgesics only. Patient's parents
      were asked to record the amount of medication administered and assess pain
      intensity with the use of a modified visual analogue scale for 3 days
      postoperatively. Parents also completed an overall pain management satisfaction
      questionnaire at the end of the study participation period. RESULTS: Fifty-four
      patients were enrolled in this study and data were analyzed on 37 patients. The
      mean daily pain intensity in the pain pump group was significantly lower for the
      day of surgery and for 2 days postoperatively, and there was an overall
      significant difference between the groups (P<0.0001). The amount of analgesic
      medication administered was significantly lower for the first 2 postoperative
      days, but there was not a significant difference between the 2 groups overall
      (P=0.29). Parent satisfaction with both pain management techniques was high and
      responses were similar between the 2 groups. CONCLUSIONS: Children with CP
      present unique postoperative pain management concerns that can be effectively
      addressed through the use of multimodal analgesic techniques. This study found
      that the pain pump is an effective pain management technique that significantly
      reduces pain intensity in children with CP after lower extremity orthopaedic
      procedures. LEVEL OF EVIDENCE: Therapeutic Level II.

PMID- 21102211
TI  - Leg length discrepancy in spastic hemiplegic cerebral palsy: a magnetic resonance
      imaging study.
AB  - BACKGROUND: In patients with spastic hemiplegic cerebral palsy (CP) it can be
      difficult to clearly define whether deviations in gait pattern result from
      impaired motor control, leg length discrepancy (LLD), or are a consequence of
      secondary compensatory mechanisms. LLD is common and treatment can be considered.
      The goal was to investigate the degree of LLD in the lower limb including the
      pelvis, femur, tibia, talus, and calcaneus using magnetic resonance imaging
      (MRI). METHODS: Forty-four patients with spastic hemiplegic CP and a mean age of
      17.6 years (range, 13.0 to 23.0 y) participated in the study; of these 20 were
      female and 24 were male. All were classified as 1 on the gross motor
      classification scale and as Winters' type 1 or 2. On the basis of sagittal T1
      weighted MRI images of the lower extremity, the length of the pelvis, femur,
      tibia, talus, and calcaneus was measured separately by 2 experienced observers
      and remeasured independently after a 2-week interval. RESULTS: Eleven of the 44
      patients had a hemiplegic lower limb that was more than 15 mm shorter. The mean
      difference was in the calcaneus (0.9 mm; P=0.003), talus (1.3 mm; P=0.006), and
      tibia (8.1 mm; P=0.000). Intraobserver comparison showed high reproducibility
      with intraclass correlation for the calcaneus (0.91), talus (0.84), tibia (0.99),
      femur (0.99), and pelvis (0.98). In the interobserver comparison, the
      corresponding inter class correlations were 0.95, 0.84, 0.99, 0.99, and 0.98.
      CONCLUSIONS: This MRI study showed LLD in teenagers and young adults with
      hemiplegic CP. The main difference between the hemiplegic and noninvolved side
      was found in the tibia, but the calcaneus and talus also showed significant
      differences. The method proved to be reliable and the measurement of LLD should
      be considered in the management of hemiplegic CP. To be able to develop rational
      treatment plans, it is of importance to know the degree and location of LLD.
      LEVEL OF EVIDENCE: Prospective cross-sectional diagnostic level 1 study.

PMID- 21102212
TI  - Operative and clinical markers of deep wound infection after spine fusion in
      children with cerebral palsy.
AB  - BACKGROUND: Infection after spine fusion for neuromuscular scoliosis has been
      shown to range from 4.2% to 20.0% prevalence. Although there are studies, which
      have examined deep wound infection and spine fusion surgery as well as risk
      factors for deep wound infection, there are limited studies evaluating clinical
      and radiographic factors associated with this complication. We aimed to determine
      the clinical and operative factors associated with deep wound infection after
      spine fusion in pediatric patients with cerebral palsy (CP). METHODS: Medical
      records of 236 pediatric patients, aged between 5.6 and 21 years (mean=13.8 +/-
      3.4), with CP who underwent spine fusion from 1995 to 2006 were reviewed. Of
      these, 22 patients had deep wound infection. To assess the differences in
      clinical, radiographic, and other predisposing factors, we used chi statistic and
      Fisher exact, and to determine the predisposing factors of deep wound infection,
      we used binomial regression model. RESULTS: The period prevalence of deep wound
      infection was 9.3%. In the unadjusted model, body weight, residual postoperative
      Cobb angle, length of hospitalization, packed red blood cells, and skin breakdown
      were the factors significantly associated with deep wound infection (P<0.05).
      After controlling for confounding, skin breakdown due to the instrumentation and
      residual postoperative Cobb angle were the 2 most potent markers of deep wound
      infection. There was a significant 4% increased risk of deep wound infection for
      1-degree increase in the residual Cobb angle from the noncase mean residual Cobb
      angle of 23.69 degrees (adjusted risk ratio=1.04; 95% confidence interval, 1.01
      1.08). Likewise, compared with those without skin breakdown, those with skin
      breakdown were 12 times as likely to develop deep wound infection (risk
      ratio=12.92; 95% confidence interval, 1.00-172.00). CONCLUSIONS: Residual
      postoperative Cobb angle and skin breakdown due to unit rod instrumentation were
      the 2 most significant predisposing factors to deep wound infection. Other
      factors included body weight, packed red blood cells, and length of
      hospitalization. As the overall prevalence of deep wound infection is relatively
      high in CP patients after spine fusion, and considering the cost of
      hospitalization and other related comorbidities, surgeons should recognize these
      predisposing parameters to prevent deep wound infection in CP patients while
      correcting curve deformities. LEVEL OF EVIDENCE: Level III retrospective study.

PMID- 21102213
TI  - Anterior femoral epiphysiodesis for the treatment of fixed knee flexion deformity
      in spina bifida patients.
AB  - BACKGROUND: Fixed knee flexion deformity is a common problem in spina bifida
      patients. Owing to interference with ambulation, this deformity may lead to
      anterior knee pain and progressive crouch gait. If conservative treatment fails,
      surgical procedures including supracondylar femoral extension osteotomy, joint
      distraction, and posterior capsulotomy have to be considered. Potential
      complications of these procedures are fractures, neurovascular lesions, knee
      instability, and recurrent deformity with continued growth. As fixed knee flexion
      deformity in spina bifida patients frequently occurs bilaterally, this results in
      higher perioperative and postoperative risks and prolonged recovery, making these
      relatively invasive methods less appealing. In the skeletal immature patient,
      anterior femoral stapling is a feasible method to treat fixed knee flexion
      deformity as could be shown in an earlier study. In this study, anterior femoral
      stapling was performed in a series of patients with diverse etiologies, and the
      overall success rate was then calculated. The aim of this study was to determine
      whether anterior femoral epiphysiodesis may improve fixed knee flexion deformity
      in a group of spina bifida patients. METHODS: Ten spina bifida patients with
      bilateral fixed knee flexion deformity (20 knees) were treated by anterior
      femoral epiphysiodesis through stapling. None of the patients received further
      knee procedures. The mean preoperative fixed knee flexion deformity was 20.3 +/-
      9.9 degrees (range: 10 to 40 degrees). Clinical and radiographic follow-up
      examinations were performed every 3 to 6 months after surgery. RESULTS: All
      patients except 1 experienced significant improvement with a mean correction rate
      of 0.9 +/- 0.5 degrees per month (range: 0.2 to 1.9 degrees). The residual
      flexion deformity averaged 5.3 +/- 5.3 degrees (range: 0 to 15 degrees; P<0.001).
      CONCLUSIONS: Anterior femoral epiphysiodesis through stapling is an effective and
      safe method for the treatment of fixed knee flexion deformity in growing children
      and adolescents with spina bifida. LEVEL OF EVIDENCE: Therapeutic Study, Level
      IV.

PMID- 21102214
TI  - Ambulation gains after knee surgery in children with arthrogryposis.
AB  - BACKGROUND: Arthrogryposis multiplex congenita is a rare congenital disorder
      associated with multiple musculoskeletal contractures that causes substantial
      morbidity. Knee involvement is commonly seen among children with arthrogryposis,
      with flexion contracture of the knee being the most frequent knee deformity. Knee
      flexion contractures in the pediatric population are particularly debilitating as
      they affect ambulation. Treatment for knee flexion contractures requires numerous
      orthopaedic procedures and an extensive follow-up period. The purpose of this
      study was to assess the effectiveness of orthopaedic procedures, namely distal
      femoral supracondylar extension osteotomy and/or Ilizarov external fixator, on
      the ambulation status of children with knee flexion contracture and whether any
      functional gains are maintained at the latest follow-up. METHODS: All children
      with arthrogryposis followed at our institution who had surgical correction for
      knee flexion contractures were included in this study. Fourteen patients were
      identified and their medical records were reviewed. The etiology for all patients
      was amyoplasia. The mean age at first surgery was 7.0 years (range, 2 to 16 y).
      The mean length of follow-up was 59.3 months (range, 12 to 117 mo). Contractures
      were treated with femoral extension osteotomy (n=8), Ilizarov external fixator
      (n=1), or both (n=5). Three patients earlier had posterior soft tissue releases,
      including hamstrings lengthenings, proximal gastrocnemius release, and release of
      posterior capsule. RESULTS: Preoperatively, 11 patients were nonambulatory, 2
      patients were household ambulators, and 1 patient walked with orthoses in the
      community. There was an average of 1.8 knee surgeries done per patient, namely
      distal femoral extension osteotomy and/or Ilizarov external fixator. At the
      latest follow-up, 8 patients were ambulatory with technical aids (orthosis,
      walker, braces, or rollator walker), 2 patients were household ambulators, 1
      patient used a wheelchair but was independent for transfers, and 3 patients
      remained nonambulatory. The mean flexion contracture before the first surgery was
      63.7 +/- 26.8 degrees. Postoperatively, the mean flexion contracture was 13.2 +/-
      16.7 degrees. At the latest follow-up, the mean flexion contracture was 34.0 +/-
      24.1 degrees. There were complications in 2 patients, including infected hardware
      which resolved with antibiotic treatment, and neurologic compromise which
      resolved on its own. CONCLUSIONS: Surgical correction of knee flexion deformities
      by distal femoral extension osteotomy and/or Ilizarov external fixator was
      effective in improving the ambulation status of children with arthrogryposis. At
      latest follow-up, the gradual loss of total arc of motion and the recurrence of
      knee flexion contractures did not limit the ambulatory gains achieved. LEVEL OF
      EVIDENCE: IV, Case series.

PMID- 21102215
TI  - Outcomes of extra-articular, intra-epiphyseal drilling for osteochondritis
      dissecans of the knee.
AB  - BACKGROUND: When conservative management fails to heal femoral condyle
      osteochondritis dissecans (OCD) lesions in a child, then drilling of the
      subchondral plate below the lesion to stimulate healing may be beneficial. This
      study reviews the outcomes of extra-articular, intraepiphyseal drilling of OCD
      lesions of the knee with intact articular cartilage. METHODS: Over an 8-year
      period, all children, who failed at least 6 months of nonoperative management,
      underwent arthroscopic knee surgery and extra-articular, intra-epiphyseal
      drilling for their symptomatic, nondisplaced femoral condyle OCD lesions. The
      clinical and radiographic outcomes were evaluated by using demographics,
      preoperative size of the lesion, intraoperative concomitant pathology,
      complications, postoperative range of motion, return to activities, radiographic
      progression of healing, and subsequent operative procedures. RESULTS: In all 59
      children, the mean time to return to activities was 2.8 months (1.3 to 13.1 mo)
      and the mean percentage of radiographic healing was 98.2% (79% to 100%) at final
      follow-up. Forty-four (75%) of the OCD lesions were successfully treated to 100%
      radiographic healing with an average time for healing of 11.9 months (1.3 to 47.3
      mo). The large lesions took significantly longer to heal than the small lesions,
      15.3 months versus 8.8 months (P=0.032), and the percentage of radiographic
      healing at final follow-up approached significance with large (>3.2 cm2) lesions
      attaining a mean of 96.9% (standard deviation 6.4%) versus small lesions (<3.2
      cm2) with a mean of 99.4% (standard deviation 2.1%, P=0.083). No operative
      complications were observed. CONCLUSIONS: Extra-articular, intraepiphyseal
      drilling of OCD lesions produced excellent results over the historical controls
      using intra-articular drilling for those patients who failed initial conservative
      management. This technique allows for more drill holes to be placed perpendicular
      to the OCD lesions, especially the posterior lesions that may have limited intra
      articular access. Furthermore, this technique avoids intraoperative damage to the
      overlying intact articular cartilage and promotes osseous healing by fenestration
      of the sclerotic rim surrounding the OCD lesion. LEVEL OF INCIDENCE: Prognostic
      study, Level IV (retrospective study).

PMID- 21102216
TI  - Increased risk of Blount disease in obese children and adolescents with vitamin D
      deficiency.
AB  - BACKGROUND: Poor dietary habits and decreased outdoor activity has led to an
      epidemic of obese children and vitamin D deficiency. The lack of vitamin D alters
      bone development and mineralization by diminishing physiological levels of
      calcium and phosphorus. Given vitamin D's role in bone and growth plate
      mineralization and regulation, we hypothesized that vitamin D deficiency would
      lead to higher rates of fractures, slipped capital femoral epiphysis (SCFE), and
      Blount disease in obese youth. METHODS: A retrospective review was performed at
      the obesity clinic using the obesity database (890 patients). Data obtained
      included body mass index (BMI), vitamin D levels (25-vitamin D), history of
      fractures, Blount disease, and/or SCFE. The chart review identified 2 populations
      of obese patients, those with vitamin D deficiency, <16 ng/mL (198 patients) and
      those not vitamin D deficient >16 ng/mL (692 patients). Fisher exact, chi2, and 2
      sample t tests along with logistic regression were used for statistical analysis.
      A P value <=0.05 was considered statistically significant. RESULTS: Blount
      disease was found to have a statistically significant (P<0.05) positive
      association with patient's sex, BMI, and vitamin D level. Specifically, males
      were 8.16 times more likely than females to be observed with Blount disease
      (P=0.01). Patients with very low vitamin D levels were 7.33 times more likely to
      have Blount disease than patients with higher levels (P=0.002). Each whole number
      increase in BMI increases the likelihood of Blount disease by 3% (P=0.01). There
      was no association between increased number of fractures or SCFE with vitamin D
      deficiency in these obese patients. CONCLUSION: As our findings indicate, BMI and
      vitamin D levels have a strong association with Blount disease, which may be
      especially important among males. Ours is the first study to show a relationship
      between vitamin D deficiency and Blount disease, but further prospective studies
      are needed with larger numbers to confirm this independent association of vitamin
      D deficiency with Blount disease. LEVEL OF EVIDENCE: Level III retrospective
      study.

PMID- 21102217
TI  - Clinical indications for repeat MRI in children with acute hematogenous
      osteomyelitis.
AB  - BACKGROUND: At our center and at others, some children with acute hematogenous
      osteomyelitis (AHO) are evaluated with multiple magnetic resonance imagings
      (MRIs) during their treatment. Do these serial MRI studies have a role in the
      management of AHO? We examine several clinical indications for ordering a repeat
      MRI and whether the imaging study resulted in a change in management. METHODS: A
      total of 59 children (60 cases) with AHO were imaged with more than 1 MRI. We
      retrospectively reviewed the MRI studies and hospital records to investigate
      whether the results of the MRIs prompted a change in clinical management
      (surgical exploration or drainage, biopsy, change in the course of antibiotics).
      We investigated several clinical indicators including C-reactive protein (CRP)
      levels, time since index study, anatomic location of infection, and blood
      cultures. Differences in the proportion of patients with specified clinical
      characteristics, whose repeat MRI resulted in a change in management, were
      assessed by the use of chi2 analysis. RESULTS: The median age of our patient
      population was 8.4 years; a total of 104 repeat MRI studies were undertaken on 59
      children. Eleven (10.6%) of these studies prompted a change in patient treatment.
      Statistically significant indications for repeat MRI in changing clinical
      management included failure to improve clinically in 10 studies (21%, P<0.001),
      persistently elevated or increasing CRP levels in 11 MRI studies (52%, P<0.001),
      and the repeat study occurring within 14 days of the diagnostic MRI in 8 studies
      (29%, P=0.003). CONCLUSIONS: The results of our study showed that additional MRI
      studies provide information that affected patient management in only a limited
      number of cases. Although repeat MRI does not have a role in routine surveillance
      in children with AHO undergoing treatment, it can be a useful adjunct to clinical
      evaluation in patients who do not respond to therapy or who have a persistently
      elevated CRP level. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

PMID- 21102218
TI  - Pediatric calcaneal osteomyelitis.
AB  - BACKGROUND: Osteomyelitis continues to be a common problem amongst the pediatric
      population. Osteomyelitis of the calcaneus is an uncommon problem that still
      poses a problem to the treating physician. The purpose of this article is to
      retrospectively review a large series of pediatric patients with calcaneal
      osteomyelitis. We compare our experience with that in the literature to determine
      any factors that may aid earlier diagnosis and or improve treatment outcomes.
      METHODS: A 10-year retrospective review was performed of clinical records of all
      cases of pediatric calcaneal osteomyelitis managed at the 2 children's
      orthopaedic departments in the Auckland region. The Osteomyelitis Database was
      used to identify all cases between 1997 and 2007, at Starship Children's
      Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital. RESULTS: Sixty
      patients fulfilled the inclusion criteria, and had a review of clinical notes and
      relevant investigations. The average duration of symptoms before presentation to
      hospital was 6.8 days. About 40% of patients had a recent episode of trauma.
      About 82% of patients could not bear weight on admission. Only 22% of patients
      had a temperature above 38 degrees C. Erythrocyte sedimentation rate was elevated
      in 81% and the C-reactive protein was elevated in 77% of patients. About 27% of
      patients had positive blood cultures with Staphylococcus aureus being the most
      commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging
      were all used to aid the diagnosis. About 20% of patients had surgery with an
      average of 1.3 surgeries for those who progressed to surgery. Treatment length
      was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2
      days of oral treatment. There were no postsurgical complications and 10
      readmissions: 3 for relapse, 3 for peripherally inserted central catheter line
      problems, and 4 for antibiotic-associated complications. CONCLUSIONS: Although
      sometimes more difficult to diagnose, calcaneal osteomyelitis can be diagnosed
      with an appropriate history, clinical examination, and investigations. Treatment
      with intravenous and oral antibiotics and surgical debridement if indicated can
      lead to a good clinical outcome with minimal complications.

PMID- 21102219
TI  - Increased incidence of sacroiliac joint infection at a children's hospital.
AB  - BACKGROUND: Pyogenic sacroiliitis (PSI) is an uncommon type of osteoarticular
      infection. A study is undertaken to confirm an observed increase in incidence of
      PSI at our pediatric institution and to evaluate any associations with increasing
      incidence of community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) infection and other factors. METHODS: All inpatients with osteoarticular
      infection were identified from the periods of 1992 to 1996 and 2004 to 2007.
      Patients with surgical site infection, immunologic deficits, decubiti, or other
      predisposing factors were excluded. Demographic, microbiologic, and clinical
      factors were analyzed for comparison. RESULTS: Overall 362 cases were included:
      205 with osteomyelitis alone and 157 with pyarthrosis, of which 15 were PSI
      cases. The incidence of PSI increased from the periods of 1992 to 1996 and 2004
      to 2007 (0.8 vs. 2.8 cases/y, P=0.03), along with osteomyelitis at pelvic and
      spinal sites (ie, axial sites; 1.6 vs. 5.0 cases/y; P=0.03), whereas the
      incidence of osteoarticular infection at other sites remained stable. CA-MRSA was
      isolated in 1 (6.7%) PSI case. In the second time period, CA-MRSA did not form a
      higher proportion of S. aureus isolates at sacroiliac or other axial sites (CA
      MRSA: 17% of S. aureus in PSI and axial osteomyelitis vs. 45% of S. aureus at
      nonaxial sites, P=0.08). Patients were older in the second time period (4.5 y vs.
      7 y; P<0.0001), and patients with PSI (10.5 y) and axial osteomyelitis (8.5 y)
      were older than those with osteoarticular infection at other sites (5.3 y;
      P<0.0001). CONCLUSIONS: The emergence of CA-MRSA does not explain the increasing
      incidence of PSI. The incidence of PSI and osteomyelitis involving the axial
      skeleton are increasing, predominantly in older patients. These trends should be
      prospectively investigated. LEVEL OF EVIDENCE: III, Prognostic Study.

PMID- 21102220
TI  - Preliminary results of calcaneofibular ligament transfer for recurrent peroneal
      subluxation in children and adolescents.
AB  - BACKGROUND: Subluxation of the peroneal tendons over the lateral malleolus is an
      uncommon condition in both pediatric and adult populations. The primary
      dislocation is thought to occur with rupture of the superior peroneal retinaculum
      and may be associated with marginal fractures of the lateral malleolus or a
      preexisting shallow groove inferiorly. Various operative techniques have been
      reported earlier, but little data exists regarding surgical management and
      outcome in a pediatric and adolescent population with open physes. METHODS: A
      retrospective review of patients presenting to our institution over a 5-year
      period yielded 9 cases of recurrent peroneal subluxation refractory to
      nonoperative management in 7 children or adolescents (mean age 12 y). Both
      traumatic and atraumatic etiologies were represented. All patients failed
      nonoperative treatment and were treated operatively with calcaneofibular ligament
      (CFL) transfer to reroute the peroneal tendons underneath the CFL. All patients
      were observed in follow-up and sent validated outcomes questionnaires, including
      the Foot and Ankle Ability Measure and the American Orthopaedic Foot and Ankle
      Society Ankle-Hindfoot Scale. RESULTS: Mean clinical follow-up was 20.9 months
      (range: 12 to 35 mo). At follow-up, all patients had returned to sports and
      activity and there were no instances of recurrence of subluxation. Complications
      included 1 postoperative infection and 1 patient requiring revision surgery for
      fibrosis. Six of 9 ankles (66.6%) returned the outcomes surveys. The average Foot
      and Ankle Ability Measure activities of daily living score was 90.8 (+/-4.4) and
      the sports subscale was 62.5 (+/-9.3). The mean American Orthopaedic Foot and
      Ankle Society score was 86 (+/-3.2). CONCLUSIONS: Peroneal subluxation is an
      uncommon condition in pediatric and adolescent athletes. CFL transfer over the
      peroneal tendons should be considered as it provides excellent stability, a low
      rate of recurrent subluxation, and good functional outcomes without risk of
      injury to the distal fibular physis which can occur with distal fibular osteotomy
      or groove deepening procedures. LEVEL OF EVIDENCE: IV (Case series).

PMID- 21102221
TI  - Symptomatic bunionette deformity in adolescents: surgical treatment with
      metatarsal sliding osteotomy.
AB  - BACKGROUND: Bunionette deformity is a painful osseous prominence on the lateral
      aspect of the head of the fifth metatarsal. The purpose of this study is to
      evaluate the results of a fifth metatarsal sliding osteotomy for the treatment of
      this deformity in patients under 18 years of age. METHODS: We retrospectively
      evaluated 13 feet in 11 consecutive patients with bunionette deformity treated
      from January 2003 to January 2008 at 2 referral centers. Mean age was 14.8 years
      (95% confidence limit, SD 1.5 y); mean follow-up was 32.2 months (95% confidence
      limit, SD 11.7 mo); and clinical evaluation was made according to the modified
      American Orthopaedic Foot and Ankle Society (AOFAS) score and the Coughlin score.
      The IV-V intermetatarsal angle ( IV-V IMA), the width of the forefoot (WF),
      lateral deviation angle (LDA), and fifth metatarsophalangeal angle (5 MPA) were
      also measured preoperatively and postoperatively. RESULTS: The average
      postoperative AOFAS score was 91 +/- 4.1 points. Seven patients (8 feet) had an
      excellent outcome and 4 patients (5 feet) a good outcome according to the
      Coughlin scoring rate. The IV-V IMA averaged 12.29 degrees +/- 1.5 degrees
      preoperatively, while postoperatively it was 6.18 degrees +/- 1.4 degrees
      (P<0.0001). The LDA improved from 7.74 degrees +/- 1.7 degrees preoperatively to
      4.25 degrees +/- 1 degree after surgery (P<0.0001). The WF decreased from 8.01 +/
      1.3 mm to 7.05 +/- 1.3 mm (P<0.0001). The mean 5 MPA decreased from 21.7 degrees
      +/- 4.1 degrees preoperatively to 7.63 degrees +/- 3.4 degrees at final follow-up
      (P<0.0001). One patient developed a superficial infection around a K-wire.
      CONCLUSIONS: Metatarsal sliding osteotomy is a safe and effective method for the
      correction of symptomatic bunionette in patients below 18 years of age. Further
      research is required to compare this approach with other treatment methods in
      this specific age group. STUDY DESIGN: Case series (Level of evidence, IV).

PMID- 21102222
TI  - Flexible intramedullary nail use in limb lengthening.
AB  - BACKGROUND: The aim of this study is to evaluate the influence of the external
      fixation associated with flexible intramedullary nailing (FIN) on the healing
      index (HI) in limb lengthening. METHODS: We compared the healing index between 2
      groups of children undergone the lengthening of upper and lower limbs carried out
      with the Ilizarov external fixator alone (group I, 194 cases of lengthening) or
      with the combination of the Ilizarov external fixator and intramedullary nailing
      (group II, 92 cases). Two nails of the diameter from 1.5 to 2.0 mm with the ray
      of curvature about 40 degrees to 50 degrees were used for the intramedullary
      nailing. RESULTS: The HI was less in every subgroup of Group II compared with
      Group I. A significant difference was noted in congenital pathologies: monofocal
      monosegmental lengthening at the level of femur and forearm, bifocal lengthening
      of the tibia, polysegmental lengthening; and in acquired discrepancy: monofocal
      tibial lengthening, bifocal femoral lengthening, and the forearm lengthening. The
      reduction of HI was between 60% and 85% in congenital pathologies: monosegmental
      femur and forearm, bifocal femur and tibia lengthening; and in acquired
      discrepancy: femur, tibia, humerus and forearm monosegmental lengthening, humerus
      and tibia bifocal lengthening, and polysegmental in upper and lower limbs. This
      difference varies from 1.9 days/cm to 19.1 days/cm. That means that the duration
      of the external fixator was decreased of 20% to 33% of the number of days between
      the Group I and the Group II. Maximum diminution of HI was noted for monofocal
      acquired forearm cases (51.3%) and bifocal acquired femoral lengthening cases
      which (59.9%). CONCLUSIONS: The flexible intramedullary nailing allows adding
      multiple advantages to the method of limb lengthening with the external fixator.
      Correctly applied the FIN indeed respects the bone biology that is essential
      during the limb lengthening. The major effect of application of the combination
      of Ilizarov frame fixation with FIN is a significant decrease of duration of the
      external osteosynthesis. LEVEL OF EVIDENCE: II.

PMID- 21102223
TI  - Long-term results in children with massive bone osteoarticular allografts of the
      knee for high-grade osteosarcoma.
AB  - BACKGROUND: Reconstruction of distal femur or proximal tibia in growing patients
      is a challenge for the high rate of complications and limb length discrepancy at
      the end of growth. The purpose of this study was to evaluate the long-term
      outcome of children affected by high-grade osteosarcoma of the knee region,
      reconstructed by osteoarticular bone allograft of distal femur, and proximal
      tibia. METHODS: We retrospectively reviewed 25 patients treated for high-grade
      osteosarcoma, 13 in the distal femur and 12 in the proximal tibia. The mean
      follow-up was 124 months. Clinical and radiologic evaluation was carried out in
      the 20 long-term survivors with a minimum follow-up of 7 years from surgery. The
      rates of survival of the implants were estimated with use of the Kaplan-Meier
      method. Functional and radiographic evaluation was done according to the
      Musculoskeletal Tumor Society scoring system at the time of the latest follow-up
      in all the patients that still had the allograft. RESULTS: Five patients died
      during the first 2 years of follow-up for disease-related causes. Of the
      remaining 20 osteoarticular allografts (10 of the distal femur and 10 of the
      proximal tibia), 12 failed: 4 in the distal femur and 8 in the proximal tibia.
      All the failures were related to a graft fracture, but in 4 patients with
      subchondral collapse the graft was maintained and converted into an allograft
      prosthetic composite. No deep infection of the primary reconstruction was
      observed. The overall rate of allograft survival was 70% at 5 years and 58% at 10
      years in the distal femur, and 45% at 5 years and 20% at 10 years in the proximal
      tibia. At final follow-up, 8 patients still walked on the primary implant, 6 in
      the distal femur, and 2 in the proximal tibia. The functional outcome of these
      patients was evaluated as good in 5 patients (3 with distal femoral and 2 with
      proximal tibial allograft), and poor in 3. CONCLUSIONS: Although mechanical
      complications significantly affect the outcome, osteoarticular allografts may
      represent a viable option for reconstruction in children older than 8 with high
      grade sarcomas about the knee. LEVEL OF EVIDENCE: Level IV.

PMID- 21102224
TI  - Correlation of magnetic resonance imaging and histologic examination of physeal
      bars in a rabbit model.
AB  - BACKGROUND: The formation of a physeal bony bridge, or bar, is frequently
      observed in pediatric patients after trauma and is visualized using magnetic
      resonance imaging (MRI). No study to date has validated the indirect MRI bar area
      measurements with direct measurements. PURPOSE: To create a physeal bar using a
      radiofrequency (RF) ablation technique in a rabbit model and to validate an
      indirect measurement of the bar area from MRIs with direct histologic
      measurements. METHODS: An epiphysiodesis procedure was performed on the proximal
      tibial growth plates of 15 skeletally immature rabbit knees using radiofrequency
      ablation. The rabbits were euthanized 6 weeks postoperatively and volumetric ex
      vivo MRIs of the knees were acquired. The physeal bar area was calculated from a
      3-dimensional reconstruction of the segmented MRIs and from matching histologic
      sections of the tibia. RESULTS: A physeal bar was successfully created in all the
      rabbits. A strong correlation, r=0.83 (P=0.0001), was found between the MRI and
      histologic surface area measurements. The mean bar area from MRI measurements was
      35.0 +/- 20.8 mm2 (mean +/- SD), and the mean bar area from histologic
      measurements was 29.8 +/- 16.1 mm2. CONCLUSIONS: This study found excellent
      correlation between the MRI and histologic physeal bar area measurements. The
      measurement differences that were found may be attributed to histologic specimen
      preparation and the geometry chosen to model the physis. CLINICAL RELEVANCE: The
      results of this study allow for the quantitative evaluation of in vivo human
      physes in future studies and development of predictive models for limb length
      discrepancy.

PMID- 21102225
TI  - Asymmetrical arthrogryposis of the upper extremity associated with congenital
      spine anomalies.
AB  - BACKGROUND: The term arthrogryposis is a descriptive term referring to a variety
      of clinical conditions characterized by multiple joint contractures. The spine
      may be involved; however, the presence of associated congenital vertebral
      abnormalities is rare. METHODS: A retrospective chart review of 6 patients with
      asymmetric upper extremity joint contractures and concomitant congenital
      scoliosis of the cervical spine was performed. RESULTS: Six patients with
      congenital anomalies of the cervical spine and asymmetric contractures of the
      upper extremities were identified. Clinical findings and radiographic studies
      were reviewed. Upper extremity involvement was contralateral to the convexity of
      the spinal curvature in 5 of the 6 cases. Reconstruction of the upper extremity
      was required in 5 of 6 patients; however, no patient required operative
      intervention for their congenital cervical scoliosis. CONCLUSIONS: Congenital
      cervical spine anomalies can be associated with asymmetric arthrogryposis of the
      upper extremities. Physicians who take care of pediatric patients with
      arthrogryposis should carefully evaluate the cervical spine. LEVEL OF EVIDENCE:
      Level IV, case series.

PMID- 21102226
TI  - Proximal humeral fractures in children and adolescents.

PMID- 21102227
TI  - Prospective evaluation of a shortened regimen of treatment for acute
      osteomyelitis and septic arthritis in children.

PMID- 21102228
TI  - Report by Swaroop and Mubarak.

PMID- 21102234
TI  - Summary of the proceedings from the 10th annual meeting of molecularly targeted
      therapy in non-small cell lung cancer.

PMID- 21102237
TI  - Fibroblast growth factor inhibitors.

PMID- 21102235
TI  - Molecular targeted agents and biologic therapies for non-small cell lung cancer.

PMID- 21102236
TI  - Poly(ADP-ribose) polymerase inhibitors.

PMID- 21102238
TI  - Histone deacetylase, proteasome, and heat shock protein inhibitors for the
      treatment of lung cancer.

PMID- 21102239
TI  - Cell cycle-associated kinases as targets for therapy in lung cancer.

PMID- 21102240
TI  - Vaccines and immunotherapy for non-small cell lung cancer.

PMID- 21102241
TI  - SRC inhibitors.

PMID- 21102242
TI  - Novel drugs--miscellaneous category.

PMID- 21102243
TI  - Epidermal growth factor receptor pathway.

PMID- 21102244
TI  - Supportive care.

PMID- 21102245
TI  - MEK/MAPK inhibitors.

PMID- 21102246
TI  - Radiotherapy.

PMID- 21102247
TI  - Insulin-like growth factor pathway.

PMID- 21102248
TI  - Proapoptotic agents in lung cancer.

PMID- 21102249
TI  - Vascular disrupting agents.

PMID- 21102250
TI  - Targeting vascular endothelial growth factor in lung cancer.

PMID- 21102251
TI  - Mammalian target of rapamycin, Akt, and phosphatidylinositol 3-kinase signaling.

PMID- 21102252
TI  - Novel taxanes/epothilones.

PMID- 21102253
TI  - Cancer stem cells and targeting embryonic signaling pathways.

PMID- 21102254
TI  - EML4/ALK and ras inhibitors.

PMID- 21102255
TI  - New territory: surgical salvage for stereotactic body radiation therapy failures
      in lung cancer.

PMID- 21102256
TI  - Salvage surgery after stereotactic radiotherapy: a new challenge for thoracic
      surgeons.

PMID- 21102257
TI  - LKB1 regulated pathways in lung cancer invasion and metastasis.
AB  - Metastasis is characterized by the ability of cancer cells to invade into
      adjacent tissue, intravasate into blood or lymphatic vessels, and extravasate
      into a distant tissue. Metastatic disease is primarily responsible for the low 5
      year survival rate of non-small cell lung cancer (NSCLC), and therefore, an
      understanding of the molecular mechanisms that regulate NSCLC metastasis is
      clearly warranted. The serine/threonine kinase and tumor suppressor LKB1 is
      mutated in 30% of NSCLC tumors, and recent evidence points to a prominent role in
      NSCLC metastasis. This review summarizes LKB1-dependent invasion pathways where
      compromised LKB1 function could promote NSCLC metastasis.

PMID- 21102259
TI  - Ligands of epidermal growth factor receptor and the insulin-like growth factor
      family as serum biomarkers for response to epidermal growth factor receptor
      inhibitors in patients with advanced non-small cell lung cancer.
AB  - INTRODUCTION: The selection of patients with non-small cell lung cancer (NSCLC)
      for epidermal growth factor receptor (EGFR) inhibitor (EGFR-tyrosine kinase
      inhibitors [TKIs]) therapy is suboptimal as tumor tissue is often unavailable.
      Ligands of EGFR, transforming growth factor-alpha (TGFa) and amphiregulin (ARG),
      and the insulin-like growth factor (IGF) family have been associated with
      resistance to EGFR-TKIs. The aim of our study was to explore whether
      concentrations of these factors measured in serum were predictive of response to
      EGFR-TKIs. METHODS: We assessed serum levels of marker candidates using enzyme
      linked immunosorbent (TGFa and ARG) and chemiluminescent (IGF1 and IGF-binding
      protein-3) assays in 61 patients with advanced NSCLC treated with EGFR-TKIs and
      63 matched advanced NSCLC control patients without EGFR-TKIs treatment. We
      dichotomized marker levels at the 20th, 50th, or 80th percentile and evaluated
      whether the effect of EGFR-TKIs treatment on disease-specific survival (DSS)
      differed by marker level based on multivariate proportional hazards regression
      with an interaction term. RESULTS: The effect of EGFR-TKIs treatment on DSS
      showed a significant difference by TGFa and ARG (interaction p = 0.046 and p =
      0.004, respectively). Low concentrations of TGFa and high concentrations of ARG
      were associated with a better DSS in EGFR-TKIs patients compared with control
      patients. Patients with high concentrations of IGF-binding protein-3 had
      significantly longer DSS, independent of treatment (hazard ratio: 0.60 per 1
      mg/liter, 95% confidence interval: 0.46-0.79). CONCLUSION: Our results suggest
      that concentrations of TGFa and ARG measured in serum are predictive of EGFR-TKI
      response. The combination of these two biomarkers could be of value in the
      process of selecting patients for treatment with EGFR-TKIs.

PMID- 21102258
TI  - Genetic and epigenetic analysis of erbB signaling pathway genes in lung cancer.
AB  - BACKGROUND: Prognosis for patients with non-small cell lung cancer (NSCLC) is
      poor. The potential value of modulating epidermal growth factor receptor (EGFR)
      for treatment is reflected by the recent approval of specific drugs that inhibit
      its activity. Mutations in EGFR were reported in lung cancer and generated
      interest, once they enable the identification of lung cancers likely to respond
      to various targeted small molecules. METHODS: We tested three key genetic and
      epigenetic alterations (EGFR, RASSF1A, and BRAF) of this pathway on a series of
      primary NSCLC (total 111; adenocarcinoma 49, squamous cell carcinoma [SCC] 48,
      and others 14). The mutational status of KRAS (and p53) was known for these
      samples. The purpose of this study was to define the pattern of erbB pathway
      alterations in NSCLC and to test for associations with clinical parameters.
      RESULTS: Five EGFR mutations were identified: three in adenocarcinoma (6%), one
      in SCC (2%), and one in adenocarcinoma with bronchoalveolar component tumor (7%).
      EGFR mutations included three in-frame deletions in exon 19 and two point
      mutations in exon 21. Promoter methylation of RASSF1A was detected in 25 of 45
      adenocarcinomas and 18 of 46 SCC. Mutations of EGFR, BRAF, and KRAS in
      adenocarcinoma were mutually exclusive and inversely correlated with RASSF1A
      methylation (p = -0.394; p = 0.007). DISCUSSION: Overall, genetic and/or
      epigenetic alterations of erbB pathway genes were detected in 80% (39/49) of
      adenocarcinomas.Approximately half of primary adenocarcinoma harbor molecular
      alterations of the erbB pathway. Careful characterization of these alterations
      and response to anti-EGFR therapies is warranted to determine better and accurate
      determinants of clinical response.

PMID- 21102260
TI  - Randomized, phase II trial of pemetrexed and carboplatin with or without
      enzastaurin versus docetaxel and carboplatin as first-line treatment of patients
      with stage IIIB/IV non-small cell lung cancer.
AB  - INTRODUCTION: Enzastaurin is an oral serine/threonine kinase inhibitor that
      targets protein kinase C-beta (PKC-beta) and the phosphatidylinositol-3
      kinase/AKT pathway. This trial assessed pemetrexed-carboplatin +/- enzastaurin to
      docetaxel-carboplatin in advanced non-small cell lung cancer. METHODS: Patients
      with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and
      performance status 0 or 1 were randomized to one of the three arms: (A)
      pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for
      up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500
      mg daily until disease progression, (B) the same regimen of pemetrexed
      carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area
      under the curve 6 once every 3 weeks for up to six cycles. The primary end point
      was time to disease progression (TTP). RESULTS: Between March 2006 and May 2008,
      218 patients were randomized. Median TTP was 4.6 months for pemetrexed
      carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months
      for docetaxel-carboplatin (differences not significant). Median survival was 7.2
      months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed
      carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank p = 0.05).
      Compared with the other arms, docetaxel-carboplatin was associated with lower
      rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4
      febrile neutropenia. CONCLUSION: There was no difference in TTP between the three
      arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel
      carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.

PMID- 21102261
TI  - Salvage lung resection for non-small cell lung cancer after stereotactic body
      radiotherapy in initially operable patients.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a curative
      treatment for medically inoperable patients with early-stage non-small cell lung
      cancer (NSCLC). Since NSCLC recurs locally in 10% of the patients treated with
      SBRT, salvage lung resection after SBRT may be considered in these cases. To
      further understand the indications for salvage surgery and the pathogenesis of
      tumor recurrence in these patients, we retrospectively reviewed cases treated at
      our institution. METHODS: SBRT has been performed in patients with early-stage
      NSCLC at Kyoto University Hospital. We encountered 5 patients who underwent
      salvage lung resection for NSCLC after SBRT. RESULTS: All the patients were
      initially operable, but they chose SBRT. After SBRT, the tumors shrank initially
      in all patients, but increased in size within 18 months of SBRT in the case of 4
      patients. During surgical extirpation, we did not find any significant SBRT
      related adhesions in any of the patients. CONCLUSIONS: We have successfully
      treated 5 patients who underwent salvage lung resection for early-stage NSCLC
      after SBRT. We found that surgical resection was feasible after SBRT.

PMID- 21102262
TI  - Surgical treatment of local recurrence after stereotactic body radiotherapy for
      primary and metastatic lung cancers.
AB  - INTRODUCTION: Stereotactic body radiotherapy (SBRT) has been proposed as an
      alternative to surgery for the treatment of lung cancer. The treatment of local
      recurrence that occurs after SBRT has not been reported. We present surgical
      outcomes for local recurrence following SBRT for primary and metastatic lung
      cancers. METHODS: Seven of the patients who received SBRT between 2002 and 2008
      underwent salvage surgery for local recurrence. These seven patients (two with
      stage I non-small cell lung cancer and five with metastatic tumors) were
      operable, although they refused surgery and chose SBRT for the first treatment as
      a less invasive procedure. RESULTS: Six of the seven patients underwent
      lobectomy, and the other patient underwent segmentectomy. None of the seven
      patients had direct pleural adhesion resulting from SBRT, although, in general,
      radiation fibrosis occurs after radiotherapy and induces pleural adhesion that
      makes surgery difficult. CONCLUSIONS: Our study suggests that SBRT may not be the
      cause of difficulties encountered during the surgical process, and surgery is a
      good alternative treatment for local recurrence after SBRT. During follow-up
      after SBRT, the appearance of tumor regrowth on lung images resembled that of
      inflammatory changes such as radiation pneumonitis. We suggest that close follow
      ups should be mandatory after SBRT.

PMID- 21102263
TI  - Paclitaxel plus bevacizumab in patients with chemosensitive relapsed small cell
      lung cancer: a safety, feasibility, and efficacy study from the Hoosier Oncology
      Group.
AB  - INTRODUCTION: Bevacizumab when combined with carboplatin and paclitaxel improves
      response rates (RRs) and overall survival in patients with advanced non-small
      cell lung cancer. Paclitaxel has single-agent activity in relapsed small cell
      lung cancer (SCLC). Angiogenesis seems to play an important role in the
      pathogenesis of SCLC. This study evaluated the safety and efficacy of paclitaxel
      plus bevacizumab in patients with chemosensitive relapsed SCLC. METHODS: Patients
      with relapsed chemosensitive SCLC with an Eastern Cooperative Oncology Group
      performance status of 0 to 1 were eligible. They received paclitaxel 90 mg/m
      intravenously on days 1, 8, and 15. Bevacizumab was administered at 10 mg/kg
      intravenously on days 1 and 15. Cycles were every 28 days. The primary endpoint
      was progression-free survival (PFS). Secondary endpoints included RRs, toxicity,
      and overall survival. Correlative studies evaluated vascular endothelial growth
      factor polymorphisms. RESULTS: Thirty-four patients were enrolled in the study.
      Median age was 66.5 (range, 38-88) years, male:female: 61.8%:38.2%, Eastern
      Cooperative Oncology Group performance status 0:1 47.1%:52.9%. Median progression
      free survival was 14.7 weeks (equivalent to historical controls). Median survival
      time was 30 weeks. The overall RR was 18.1%. Stable disease rate was 39.3%, and
      45.4% of patients had progressive disease. No unexpected toxicities were noted,
      and grade 3/4 toxicities were limited to neutropenia, fatigue, and dyspnea. None
      of the vascular endothelial growth factor polymorphisms evaluated were
      significantly associated with response. CONCLUSIONS: The addition of bevacizumab
      to paclitaxel does not improve outcomes in relapsed chemosensitive SCLC.

PMID- 21102264
TI  - Primary malignant pericardial mesothelioma mimicking pericardial metastasis from
      adenocarcinoma.

PMID- 21102265
TI  - Long-lasting drop in perfusion of a non-small cell lung cancer induced by
      monotherapy with the epithelial growth factor receptor inhibitor erlotinib
      persisting despite tumor progression at remote sites.

PMID- 21102266
TI  - Clinical effectiveness of boron neutron capture therapy for a recurrent malignant
      peripheral nerve sheath tumor in the mediastinum.

PMID- 21102267
TI  - Good response to gefitinib in lung adenocarcinoma harboring coexisting EML4-ALK
      fusion gene and EGFR mutation.

PMID- 21102268
TI  - Treatment of lung cancer with an ALK inhibitor after EML4-ALK fusion gene
      detection using endobronchial ultrasound-guided transbronchial needle aspiration.

PMID- 21102269
TI  - Rapid and dramatic radiographic and clinical response to an ALK inhibitor
      (crizotinib, PF02341066) in an ALK translocation-positive patient with non-small
      cell lung cancer.

PMID- 21102271
TI  - Re: Hohl JB, Lee JY, Horton JA, et al. A novel classification system for
      traumatic central cord syndrome: the Central Cord Injury Scale (CCIS). Spine
      (Phila Pa 1976) 2010;35:E238-43.

PMID- 21102272
TI  - Vertebral osteoporosis: perfused animal cadaver model for testing new
      vertebroplastic agents.
AB  - STUDY DESIGN: Experimental study. OBJECTIVE: It was aimed to establish a cadaver
      model to imitate osteoporotic perfused vertebral bone and to allow for
      transpedicular transfer of bone cement and various new materials into vertebrae.
      The model was perfused to simulate vertebroplasty in the presence of
      transvertebral blood flow. SUMMARY OF BACKGROUND DATA: The injection of bone
      cement into vertebrae bears the risk of irreversible discharge of material into
      the venous system of the spinal canal. The bovine cadaver model studied allows
      visual studies of material distribution in a vertebral bone, the potential spill
      out of material, and quantification of washout and disintegration phenomena.
      METHODS: Thoracic and lumbar vertebrae from 1-year-old calves were cut
      transversally into 5 mm slices, macerated, and decalcified. The softened bone
      slices were compressed between 2 transparent plastic discs. A standard
      vertebroplasty cannula (outer diameter 3.5 mm, inner diameter 2.5 mm) was
      inserted into the vertebral body via the pedicle to transfer the different
      vertebroplasty materials. Arterial blood flow was simulated by means of liquid
      irrigation via 2 needles in the ventral part of the vertebral body slice. Metal
      powder was mixed with the solution to indicate the blood flow in the bone. The
      model was evaluated with the vertebroplasty cement polymethylmethacrylate.
      RESULTS: The model permitted visualization of the insertion and distribution of
      vertebroplasty materials. Liquid bone cement was effused into the spinal canal as
      in the clinical situation. Higher modulus cement acted in the same way as in
      clinical vertebroplasty. Rigid vertebroplasty agents led to trabecular fractures
      and stable mechanical interactions with the bone and eventually moved dorsal bone
      fragments into the spinal canal. Sedimentation of the metal powder indicated
      regions of perfusion. CONCLUSION: The model simulated the clinical behavior of
      liquid and higher modulus vertebroplasty agents in the presence of blood flow. It
      enabled safe ex vivo testing of the mechanical and physical properties of
      alternative vertebroplasty materials under flow conditions.

PMID- 21102273
TI  - Validation of DNA-based prognostic testing to predict spinal curve progression in
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Validation of a prognostic DNA marker panel. OBJECTIVE: The goals
      of this study were to develop and test the negative predictive value of a
      prognostic DNA test for adolescent idiopathic scoliosis (AIS) and to establish
      clinically meaningful endpoints for the test. SUMMARY OF BACKGROUND DATA:
      Clinical features do not adequately predict which children diagnosed with minimal
      or mild AIS will have the progressive form of the disease; genetic markers
      associated with curve progression might offer clinically useful prognostic
      insights. METHODS: Logistic regression was used to develop an algorithm to
      predict spinal curve progression incorporating genotypes for 53 single nucleotide
      polymorphisms and the patient's presenting spinal curve (Cobb angle). Three
      cohorts with known AIS outcomes were selected to reflect intended-use populations
      with various rates of AIS progression: 277 low-risk females representing a
      screening cohort, 257 females representing higher risk patients followed at
      referral centers, and 163 high risk males. DNA was extracted from saliva, and
      genotypes were determined using TaqMan assays. AIS Prognostic Test scores ranging
      from 1 to 200 were calculated. RESULTS: Low-risk scores (<41) had negative
      predictive values of 100%, 99%, and 97%, respectively, in the tested populations.
      In the risk model, we used cutoff scores of 50 and 180 to identify 75% of
      patients as low-risk (<1% risk of progressing to a surgical curve), 24% as
      intermediate-risk, and 1% as high-risk. CONCLUSION: Prognostic testing for AIS
      has the potential to reduce psychological trauma, serial exposure to diagnostic
      radiation, unnecessary treatments, and direct and indirect costs-of-care related
      to scoliosis monitoring in low-risk patients. Further improvements in test
      performance are expected as the optimal markers for each locus are identified and
      the underlying biologic pathways are better understood. The validity of the test
      applies only to white AIS patients; versions of the test optimized for AIS
      patients of other races have yet to be developed.

PMID- 21102274
TI  - Multidirectional flexibility of the spine following posterior decompressive
      surgery after single-level cervical disc arthroplasty: an in vitro biomechanical
      investigation.
AB  - STUDY DESIGN: In vitro human cadaveric biomechanical study. OBJECTIVE: This study
      quantifies the multidirectional flexibility of the spine following laminoplasty
      and laminectomy after cervical disc arthroplasty. SUMMARY OF BACKGROUND DATA:
      Posterior decompressive surgery may be used to treat recurrence of
      myeloradiculopathy following disc arthroplasty. This is the first study
      investigating the biomechanical effects of posterior decompressive surgery
      combined with cervical disc arthroplasty. METHODS: Seven human cervical spines
      were biomechanically evaluated under the following conditions: (1) intact; (2)
      discectomy (C5-C6); (3) disc arthroplasty (C5-C6); (4) arthroplasty + 3-level
      laminoplasty (C3-C5); (5) arthroplasty + 4-level laminoplasty (C3-C6); (6)
      arthroplasty + 5-level laminoplasty (C3-C7); (7) arthroplasty + 5-level
      laminoplasty (C3-C7) without hydroxyapatite spacers; and (8) arthroplasty +
      laminectomy (C3-C7). Multidirectional flexibility testing used unconstrained pure
      moments of +/-2 Nm for flexion-extension, axial rotation, and lateral bending.
      Quantification of C5-C6 and C3-C7 range of motion (ROM) and neutral zone (NZ)
      were normalized to the intact spine (100%). RESULTS: Flexion-extension loading of
      the discectomy condition demonstrated ROM of 22.05 degrees  +/- 4.17 degrees  at
      the operative level (P < 0.05). Implantation of the porous coated motion device
      restored segmental motion near the intact condition (ROM, 9.97 degrees  +/- 6.44
      degrees ; NZ, 5.82 degrees  +/- 6.18 degrees ). There were no statistical
      differences between 3-level (13.79 degrees  +/- 6.49 degrees ), 4-level (14.51
      degrees  +/- 5.76 degrees ), and 5-level (15.67 degrees  +/- 5.71 degrees )
      laminoplasty; however, additional levels demonstrated a trend toward increased
      motion at the arthroplasty level. Laminoplasty without spacers (17.45 degrees )
      and laminectomy (18.27 degrees ) indicated even greater segmental motion (P >
      0.05). Axial rotation and lateral bending indicated trends similar to those for
      flexion-extension. CONCLUSION: Posterior decompressive surgery increased ROM and
      NZ in all loading modes compared to arthroplasty alone, and laminectomy markedly
      increased motion compared with laminoplasty. Use of hydroxyapatite spacers and
      minimization of the extent of laminoplasty appear to be biomechanically favorable
      in this in vitro model.

PMID- 21102275
TI  - Back pain is associated with changes in loading pattern throughout forward and
      backward bending.
AB  - STUDY DESIGN: Experimental study to determine the kinetics of the lumbar spine
      (LS) and hips during forward and backward bending. OBJECTIVE: To investigate the
      effects of back pain, with and without a positive straight leg raise (SLR) sign,
      on the loading patterns in the LS and hip during forward and backward bending.
      SUMMARY OF BACKGROUND DATA: Forward and backward bending are important components
      of many functional activities and are part of routine clinical examination.
      However, there is a little information about the loading patterns during forward
      and backward bending in people with back pain with or without a positive SLR
      sign. METHODS: Twenty asymptomatic participants, 20 back pain participants, and
      20 participants with back pain and a positive SLR sign performed 3 continuous
      cycles of forward and backward bending. Electromagnetic sensors were attached to
      body segments to measure their kinematics while 2 nonconductive force plates
      gathered ground reaction force data. A biomechanical model was used to determine
      the loading pattern in LS and hips. RESULTS: Although the loading on the LS at
      the end of the range decreased significantly, the loading at the early and middle
      ranges of forward bending actually increased significantly in people with back
      pain, especially in those with positive SLR sign. This suggests that resistance
      to movement is significantly increased in people with back pain during this
      movement. CONCLUSION: This study suggested that it is not sufficient to study the
      spine at the end of range only, but a complete description of the loading
      patterns throughout the range is required. Although the maximum range of motion
      of the spine is reduced in people with back pain, there is a significant increase
      in the moment acting through the range, particularly in those with a positive SLR
      sign.

PMID- 21102276
TI  - Is platelet-derived growth factor-BB expression proportional to fibrosis in the
      hypertrophied lumber ligamentum flavum?
AB  - STUDY DESIGN: A clinical and experimental assessment using human samples of
      lumbar ligamentum flavum (LF). OBJECTIVE: To identify platelet-derived growth
      factor-BB (PDGF-BB) expression in hypertrophied LF of patients with lumbar spinal
      canal stenosis (LSS) and relate it to fibrosis. SUMMARY OF BACKGROUND DATA:
      Recent studies showed that fibrosis in LF hypertrophy was due to accumulation of
      inflammation-related scar tissue. PDGF-BB participates in scar formation and
      collagen development in wound healing and fibrosis diseases. However, it is
      unclear whether PDGF-BB expression is associated with fibrosis of the
      hypertrophied LF in LSS. METHODS: In all, 10 patients of LSS was enrolled in this
      study, while 10 patients of lumbar disc herniation (LDH) as a control group. LF
      thickness was measured by axial T1-weighted magnetic resonance imaging. Fibrosis
      was graded and type of collagen was identified. The location and the expression
      of PDGF-BB were analyzed using immunohistochemical stains, real-time polymerase
      chain reaction, and Western Blotting. Correlation among LF thickness, fibrosis,
      and PDGF-BB expression was analyzed. RESULTS: LF thickness was 5.3 +/- 1.0 mm
      (range from 3.9 to 7.5 mm) in the LSS group and 2.8 +/- 0.7 mm (range from 1.69
      to 3.8 mm) in the LDH group. Obvious fibrosis was observed in all samples of the
      LSS group, and correlated to LF thickness of the dural, middle, and dorsal layers
      (P < 0.05), respectively. PDGF-BB was detected in the hypertrophied LF,
      particularly in the dorsal layer. PDGF-BB expression was higher in the LSS group
      than that in the LDH group (P < 0.05), and in the dorsal layer than the dural
      layer in the LSS group (P < 0.05). PDGF-BB mRNA correlated significantly to
      thickness of LF (r = 0.41) and the severity of fibrosis (r = 0.69) (P < 0.05).
      CONCLUSION: A higher PDGF-BB expression existed in the hypertrophied LF of
      patients with LSS and could be a risk factor of the fibrosis.

PMID- 21102277
TI  - Lordosis restoration after Smith-Petersen osteotomies and interbody strut
      placement: a radiographic study in cadavers.
AB  - STUDY DESIGN: Six human lumbar cadaveric specimens evaluated after sequential
      steps in restoration of lumbar lordosis. OBJECTIVE: To determine the effect of
      Smith-Petersen osteotomies (SPO) with concurrent interbody strut placement on
      lordosis in the lumbar spine. SUMMARY OF BACKGROUND DATA: The importance of
      restoration of lumbar lordosis is well recognized. SPO have been suggested to
      yield roughly 10 degrees  of lordosis per level, whereas pedicle subtraction
      osteotomies have been shown to result in over 30 degrees  of lordosis
      restoration. Though the pedicle subtraction osteotomy can achieve greater degrees
      of lordosis, there is considerable surgical morbidity associated. We hypothesize
      that SPO with an interbody strut placed within the disc space will result
      significantly greater lordosis than SPO alone. METHODS: Lateral radiographs of 6
      human lumbar specimens were obtained after 3 interventions as follows: (1) lumbar
      spine without osteotomy in maximal extension, (2) after SPO at L2, L3, and L4 and
      held in maximal extension with pedicle screw fixation, and (3) after SPO at L2,
      L3, and L4 with interbody cage placement in L2-L3, L3-L4, and L4-L5 held in
      maximal extension with pedicle screw fixation. RESULTS: The mean lordosis in the
      intact specimens was 7.03 degrees  (standard deviation [SD], 2.21 degrees ). The
      mean lordosis after SPO was 11.05 degrees  (SD, 1.05 degrees ). The mean lordosis
      after SPO and interbody strut placement was 15.72 degrees  (SD, 3.19 degrees ).
      The difference in lordosis in the osteotomized specimens with and without
      interbody strut was significantly (P < 0.01). CONCLUSION: The addition of an
      interbody strut to a lumbar level after SPO may result in as much as 15 degrees 
      of lumbar lordosis, significantly greater than that of SPO alone.

PMID- 21102278
TI  - Referral criteria for school scoliosis screening: assessment and recommendations
      based on a large longitudinally followed cohort.
AB  - STUDY DESIGN: This study was a retrospective cohort study. OBJECTIVE: To examine
      the criteria recommended in the literature for the school-based scoliosis
      screening program in Hong Kong. SUMMARY OF BACKGROUND DATA: School-based
      screening for scoliosis has been a controversy. Objectors to the policy were
      concerned about the high over-referral and false-positive rates. Recommendations
      were then made for improvement, but the feasibility of these recommendations has
      not been studied. METHODS: The cohort consisted of students in Grade 5 in
      1995/1996 or 1996/1997 who underwent scoliosis screening in Hong Kong.
      Participants who had an angle of trunk rotation (ATR) >=15 degrees , 2 or more
      moire lines, or presented significant clinical signs were referred for
      radiography. Screening histories and radiography records before the age of 19
      years were extracted. The accuracy measures for different combinations of
      screening tests were examined. RESULTS: There were 115,178 students in the
      cohort, of which 3228 (2.8%) were referred for radiography. Among the 1406
      students who displayed a curve >=20 degrees  during screening, 257 (18.3%) were
      boys and 336 (23.9%) were identified as 16 years or older, ruling out the
      suggestion of screening only 10-year-old girls. The sensitivity and positive
      predictive value for the current referral criteria were 88.1% and 43.6%,
      respectively. The sensitivity would drop substantially if the use of moire
      topography (39.8%) or clinical signs (55.5%) were discarded. With the inclusion
      of these 2 tests, the clinical effectiveness measures were robust to the cutoff
      for ATR, unless it was set below 10 degrees . CONCLUSION: Selectively screening
      only premenarche girls was not feasible, as this screen would have missed a
      significant proportion of children with significant curvature. No refinement of
      the current protocol was necessary, although boys could be screened beginning at
      12 years of age. The tandem use of ATR, moire topography, and clinical signs was
      recommended for future studies.

PMID- 21102279
TI  - Lumbar interspinous spacers: a systematic review of clinical and biomechanical
      evidence.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate the current biomechanical
      and clinical evidence available on the use and effectiveness of lumbar
      interspinous devices and to recommend indications for their use. SUMMARY OF
      BACKGROUND DATA: Lumbar interspinous spacers (ISPs) have recently become popular
      as an alternative treatment for lumbar degenerative disease. Several spacers are
      currently available in the market and there have been various proposed
      indications. The relevant biomechanical and clinical papers are analyzed.
      METHODS: A systematic review of clinical and biomechanical studies was done using
      the following key words: interspinous implants, interspinous devices,
      interspinous spacers, dynamic stabilization, X-STOP, Coflex, Wallis, DIAM. The
      database inclusions were MEDLINE, CINAHL (Cumulative Index to Nursing and Allied
      Health Literature), and PubMed. The main outcome measure was clinical outcome
      assessment based on validated patient-related questionnaires. Biomechanical
      studies were analyzed to evaluate the effects of ISPs on the kinematics of the
      spine. The methodology of the clinical studies was also analyzed. RESULTS:
      Largest number of studies has been with the X-STOP device. The biomechanical
      studies with all the devices showed that ISPs have a beneficial effect on the
      kinematics of the degenerative spine. Apart from 2 randomized controlled trials,
      the other studies with the X-STOP device were not of high methodologic quality.
      Nevertheless, analysis of these studies showed that X-STOP may improve outcome
      when compared to nonoperative treatment in select group of patients aged 50 or
      over, with radiologically confirmed lumbar canal stenosis and neurogenic
      claudication, who have improvement of their symptoms in flexion. Studies on the
      other devices show satisfactory outcome to varying degrees. However, due to small
      number and poor design of the studies, it is difficult to clearly define
      indications for their use in lumbar degenerative disease. CONCLUSION: Lumbar ISPs
      may have a potential beneficial effect in select group of patients with
      degenerative disease of the lumbar spine. However, further good quality trials
      are needed to clearly outline the indications for their use.

PMID- 21102280
TI  - Using segmental renal artery as recipient artery for spinal reconstructive
      surgery.
AB  - STUDY DESIGN: Report of the use of one segmental artery from the left renal
      artery as inflow source for reconstructing a spine with recalcitrant
      osteomyelitis. OBJECTIVE: To describe one difficult case of spinal osteomyelitis
      and our reconstruction procedure. SUMMARY OF BACKGROUND DATA: The use of a
      vascularized fibular flap for spinal osteomyelitis has been reported previously,
      with vascular graft having a higher successful rate of bone union and overcoming
      poor perfusion beds. Because repeated spinal surgery may lead to severe scarring,
      the choice of recipient vessels may become a difficult issue. METHODS: A 49-year
      old man with T12-L1 vertebral osteomyelitis experienced progressive spinal cord
      involvement. Because previous multiple sessions of antibiotic treatment and
      surgery proved unsuccessful, a 2-stage surgery was planned. Posterior lateral
      fusion from T9 to L3 with MOSS Miami spine system (DePuy, Spine Inc, Raynham, MA)
      and allogenous bone graft were performed, followed by anterior debridement and
      reconstruction with free vascularized fibular graft 1 week later. End-to-side
      vascular anastomosis was performed between the peroneal artery and the upper
      anterior segment artery of the left renal artery. RESULTS: After more than 50
      months follow-up, the patient was able to walk smoothly without the aid of a
      brace, walker, or crutches. There were no complications, and the radiograph
      showed good bony union. Furthermore, renal function was normal. CONCLUSION: The
      segmental renal artery can be selected as one of the recipient vessels in spinal
      reconstruction surgery without detrimental effect on renal function in our case.
      The use of vascularized fibular flap is preferable in cases of recalcitrant
      spinal osteomyelitis. Staged surgery in the presence of spinal infection can
      offer good spinal stability and good bony union with lower infection risk.

PMID- 21102281
TI  - Unusual association of ankylosing spondylitis with congenital spinal deformity.
AB  - STUDY DESIGN: In all, 4 cases of the coexistence of congenital spinal deformity
      (CSD) and ankylosing spondylitis (AS) were reviewed. OBJECTIVE: To provide an
      insight into the unusual association between CSD and AS. SUMMARY OF BACKGROUND
      DATA: CSD combined with musculoskeletal anomalies, including clubfeet, Sprengel
      deformity, Klippel-Feil syndrome, and developmental dysplasia of the hip, has
      been described in the literature. Additionally, the rare coexistence between AS
      and other inflammatory joint diseases, such as systemic lupus erythematosus,
      mixed connective tissue disease, or Behcet disease, has also been reported.
      However, to the authors' knowledge, the coexistence of CSD and AS has not been
      described in the literature. METHODS: In all, 4 patients presented with symptoms
      of lower back pain for at least 1 year. Among them, 3 patients (cases 1, 2, and
      3) were initially diagnosed as CSD, and classified as butterfly vertebra in 2
      patients (case 1, case 3), incarcerated hemivertebra in 1 patient (case 2).
      Furthermore, a diagnosis of coexistence of CSD and AS was proposed in these 3
      cases with a delay in the diagnosis of AS for 1 to 10 years. The fourth patient
      sought initial medical attention in our hospital without delay in diagnosis. In
      case 1, polysegmental Smith-Petersen osteotomy and transpedicular fixation were
      performed, and drugs were administrated. Case 2, case 3, and case 4 were treated
      with amethopterin, folic acid, salicylazosulfapyridine, and celecoxib. RESULTS:
      At the latest follow-up, 4 patients had no back pain and were satisfied with the
      outcome. CONCLUSION: The coexistence of CSD and AS is very rare. However, it is
      necessary to consider the diagnosis of AS in CSD patients who present with
      symptoms such as inflammatory low back pain, morning stiffness, loss of global
      sagittal balance, and other clinical features can not be exclusively explained by
      CSD solely.

PMID- 21102282
TI  - Spinal cord compression from a foreign body reaction to spinal cord stimulation:
      a previously unreported complication.
AB  - STUDY DESIGN: Case study. OBJECTIVE: The study presents a complication that is
      thought to have never before been reported with this therapeutic intervention.
      Results from this report are discussed with intentions to inform the
      neurosurgery, spine and pain management community of an additional complication
      associated with spinal cord stimulation (SCS). SUMMARY OF BACKGROUND DATA: SCS is
      a common intervention used to treat refractory neuropathic pain. Complications
      from this procedure are uncommon, but they do occur. METHODS: A unique
      complication of SCS was identified and treated. A search of the entire
      PubMed/Medline database failed to find any similar such complication. RESULTS: An
      epidural mass which caused significant cervical stenosis and spinal cord
      compression at the site of a previous SCS electrode was identified. Decompressive
      laminectomies and resection of the mass were performed. The mass was
      characterized as fibrous tissue with foreign body giant cell reaction.
      CONCLUSION: This is a unique complication of SCS about which all professionals
      evaluating patients who have similar implanted devices, even if they have already
      been removed, should be made aware of.

PMID- 21102283
TI  - "Beware man's best friend".
AB  - STUDY DESIGN: Case report. OBJECTIVE: To illustrate the usefulness of broad-range
      bacterial polymerase-chain-reaction (PCR) testing in osteoarticular infections by
      Capnocytophaga canimorsus. SUMMARY OF BACKGROUND DATA: C. canimorsus is a gram
      negative bacillus that was first identified in 1976. It is a normal inhabitant of
      the oral mucosa of dogs (26%) and cats (15%). The main clinical patterns are
      septicemia, which may cause fatal septic shock (in 30% of cases) but arthritis
      and discitis are possible. C. canimorsus is susceptible to many antimicrobials
      including beta-lactam antibiotics. METHODS: About a case report of 54-year-old
      man transferred to our institution for discitis, we discuss about PCR for C.
      canimorsus discitis diagnosis. RESULTS: At admission, the only abnormal physical
      finding was global pain and stiffness of the lumbar spine. Radiographs of the
      lumbar spine and pelvis showed lumbar spondylosis, degenerative disc disease, and
      previously known degenerative facet joint disease. Magnetic resonance imaging
      indicated L3-L4 discitis with damage to both vertebrae and adjacent discs.
      Findings were negative from blood and urine cultures, serological tests for the
      HIV and brucellosis, and sputum tests for Mycobacterium tuberculosis. A
      percutaneous biopsy of the L3-L4 disc was performed but the bacteriological
      studies recovered no organisms. A second needle biopsy was performed for broad
      range 16S rDNA PCR testing, which identified C. canimorsus. CONCLUSION: Broad
      range PCR provided the microbiological diagnosis of culture-negative discitis in
      our patient. Broad-range PCR should be considered in patients with culture
      negative osteoarticular infections.

PMID- 21102284
TI  - DuraSeal-hematoma: concealed hematoma causing spinal cord compression.
AB  - STUDY DESIGN: Case description. OBJECTIVE: To present a case report which
      highlights a complication following the use of Duraseal in posterior cervical
      surgery. SUMMARY OF BACKGROUND DATA: Duraseal is increasingly used to repair
      cranial and spinal dural defects to prevent cerebrospinal fluid leakage. Although
      it is well established that the hydrogel expands after implantation and may
      result in compressive effects, the phenomenon of Duraseal-entrapped hematoma has
      not previously been reported. METHODS: The authors report a 80-year-old woman who
      presented with cervical myelopathy secondary to canal stenosis. The patient
      underwent decompressive cervical laminectomies. The surgery was complicated by an
      unintended durotomy. A thin layer of Duraseal was applied over the dural surface
      and a suction drain placed before wound closure. The patient awoke from surgery
      without any new neurologic deficits but experienced delayed functional
      deterioration. Urgent magnetic resonance imaging demonstrated an extradural
      hematoma with severe cord compression. RESULTS: The patient underwent urgent
      surgery. Intraoperatively, the Duraseal was found to have formed a restrictive
      layer, completely entrapping the extradural hematoma with resultant spinal cord
      compression. Minimal blood clot was found external to the hydrogel layer.
      CONCLUSION: Although Duraseal can provide an effective and water-tight dural
      repair, it also has the potential to "entrap" extradural bleeding which otherwise
      may have been evacuated by a wound drain placed under suction. Our experience has
      shown that Duraseal should be used judiciously with recognition of this potential
      complication.

PMID- 21102285
TI  - A case of myositis ossificans in the upper cervical spine of a young child.
AB  - STUDY DESIGN: Case report. OBJECTIVE: We present a case of myositis ossificans
      (MO) of the upper cervical spine in a young child. The literature is reviewed
      with the classification, etiology, and treatment of MO discussed. SUMMARY OF
      BACKGROUND DATA: Calcification of joint capsule, muscle, cartilage, and ligaments
      is a well-known phenomenon and is known as myositis ossificans. It is very rarely
      seen in the head and neck, with no reports of MO of the soft tissues surrounding
      the first 2 cervical vertebrae. METHODS: An 8-year-old boy presented with severe
      neck pain after a fall. He had had a similar neck injury 4 years before, but made
      a full recovery. Radiographs showed a large ossified lesion between the posterior
      elements of C1 and C2. After further imaging, a diagnosis of MO was made.
      RESULTS: The child was treated with simple analgesia and observation. With no
      evidence of neurologic compromise and minimal symptoms, there was no indication
      for surgical intervention. CONCLUSION: Although rare, MO should be suspected as
      one of the possible causes of persistent pain following cervical spine injury in
      children. We would advise a low threshold for cervical spine imaging in the child
      presenting with persistent neck pain and stiffness, even years after injury.

PMID- 21102286
TI  - Acute exertional lumbar paraspinal compartment syndrome.
AB  - STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To report a
      rare case of paraspinal compartment syndrome that presented a diagnostic
      challenge. SUMMARY OF BACKGROUND DATA: Paraspinal compartment syndrome is a rare
      condition defined as increased pressure within a closed fibro-osseous space,
      resulting in reduced blood flow and tissue perfusion in that space. The reduced
      perfusion causes ischemic pain and irreversible damage to the tissues of the
      compartment if unrecognized or left untreated. METHODS: A 20-year-old African
      American man presented with 2 days of new-onset progressive back pain after
      repetitive lifting of 235 lbs in a deadlift exercise. The patient had
      significantly tender lumbar paraspinal muscles, was unable rise from a supine
      position, and had severe pain with attempted active rolling or sitting. Findings
      of supine radiographs were normal. Findings of initial laboratory investigations
      were consistent with rhabdomyolysis and acute kidney injury. Despite aggressive
      hydration and narcotic analgesia, the patient's creatinine kinase and myoglobin
      continued to rise and his pain continued to worsen. Computed tomography of the
      spine revealed enlarged paraspinal musculature and decreased enhancement
      bilaterally. Gadolinium-enhanced magnetic resonance imaging of the spine showed
      increased T2 signal and paraspinal muscle edema with areas of decreased contrast
      uptake, consistent with ischemia and necrosis. Compartment pressures measured 78
      mm Hg on the left and 26 mm Hg on the right. RESULTS: Because hydration and
      analgesia had failed, the patient was taken urgently to the operating room for
      bilateral paraspinal fasciotomies with delayed closure. His symptoms and
      rhabdomyolysis then resolved during the next 2 days. CONCLUSION: The diagnostic
      challenge presented by this case, especially considering the rarity of paraspinal
      compartment syndrome, indicates the need for a high index of suspicion in the
      appropriate setting.

PMID- 21102289
TI  - Complications in spinal deformity surgery. Summary statement.

PMID- 21102287
TI  - Penetrating spinal injury with a wooden fragment: a case report and review of the
      literature.
AB  - STUDY DESIGN: Case description. OBJECTIVES: To present a case of a missed
      diagnosis of penetrating spine injury by wood and review of the literature.
      SUMMARY OF BACKGROUND DATA: Penetrating spinal injuries by wood are rare
      injuries. Less than 10 cases with penetrating spine injuries by a wooden fragment
      had been reported earlier. METHODS: A 23-year-old man had fallen from 3 m high
      tree and sustained a penetrating wound on his right lower back. As the direct
      radiographic evaluation was normal, the diagnosis of foreign body was missed.
      Eventually, the diagnosis was made on admission of the patient with purulent
      discharge from his wound, 1-week postprimary closure. Hypoesthesia of S1, S2, and
      S3 alone, were noted neurologically. The computed tomography and magnetic
      resonance imaging of patient revealed an intraspinal foreign body pierced through
      the S1-S2 interlaminary space. Extraction of the wooden fragment was then
      performed by limited S1 laminectomy and the dural defect was also repaired.
      RESULTS: With appropriate antibiotherapy, patient recovered, with no sequela.
      CONCLUSION: Due to its density and radiologic properties, it is not unusual for
      wood to be overlooked, unless detailed imaging with computed tomography or
      magnetic resonance imaging is used.

PMID- 21102290
TI  - Intraoperative electrophysiological monitoring in spine surgery.
AB  - STUDY DESIGN: Review of the literature with analysis of pooled data. OBJECTIVE:
      To assess common intraoperative neuromonitoring (IOM) changes that occur during
      the course of spinal surgery, potential causes of change, and determine
      appropriate responses. Further, there will be discussion of appropriate
      application of IOM, and medical legal aspects. The structured literature review
      will answer the following questions: What are the various IOM methods currently
      available for spinal surgery? What are the sensitivities and specificities of
      each modality for neural element injury? How are the changes in each modality
      best interpreted? What is the appropriate response to indicated changes?
      Recommendations will be made as to the interpretation and appropriate response to
      IOM changes. SUMMARY OF BACKGROUND DATA: Total number of abstracts identified and
      reviewed was 187. Full review was performed on 18 articles. METHODS: The MEDLINE
      database was queried using the search terms IOM, spinal surgery, SSEP, wake-up
      test, MEP, spontaneous and triggered electromyography alone and in various
      combinations. Abstracts were identified and reviewed. Individual case reports
      were excluded. Detailed information and data from appropriate articles were
      assessed and compiled. RESULTS: Ability to achieve IOM baseline data varied from
      70% to 98% for somatosensory-evoked potentials (SSEP) and 66% to 100% for motor
      evoked potentials (MEP) in absence of neural axis abnormality. Multimodality
      intraoperative neuromonitoring (MIOM) provided false negatives in 0% to 0.79% of
      cases, whereas isolated SSEP monitoring alone provided false negative in 0.063%
      to 2.7% of cases. MIOM provided false positive warning in 0.6% to 1.38% of cases.
      CONCLUSION: As spine surgery, and patient comorbidity, becomes increasingly
      complex, IOM permits more aggressive deformity correction and tumor resection.
      Combination of SSEP and MEP monitoring provides assessment of entire spinal cord
      functionality in real time. Spontaneous and triggered electromyography add
      assessment of nerve roots. The wake-up test can continue to serve as a supplement
      when needed. MIOM may prove useful in preservation of neurologic function where
      an alteration of approach is possible. IOM is a valuable tool for optimization of
      outcome in complex spinal surgery.

PMID- 21102291
TI  - Establishing a standard of care for neuromonitoring during spinal deformity
      surgery.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: This article presents a critical
      examination of standard of care (SOC) related to intraoperative neurophysiologic
      monitoring during spine surgery. Definition of SOC and its applications in the
      surgical setting is accompanied by discussions on SOC for neuromonitoring,
      credentialing of neuromonitoring personnel, off-site remote monitoring, and
      unattended surgeon-controlled neuromonitoring devices. METHODS: A literature
      review of neuromonitoring and SOC over the past 10 years was performed. This
      information, in conjunction with the author's experience and evidence-based
      medicine, was used to formulate a framework for critique and discussion.
      CONCLUSION: An appropriate SOC as it relates to neuromonitoring is difficult to
      devise because of national variance with regard to qualifications of
      neurophysiologic technical and professional personnel, different levels of
      training and certification, and anesthesia protocols. A unified group of surgeons
      working in collaboration with a multidisciplinary group of experienced doctoral
      level nonphysician and physician professional surgical neurophysiologists is
      needed to define a protocol for providing and interpreting such data. In addition
      to ensuring that only the most qualified and experienced personnel are delivering
      and/or interpreting neuromonitoring services, surgeons, hospital administrators,
      and insurance company medical directors need to understand the different service
      delivery models and their respective strengths and limitations with particular
      attention to the qualifications and competencies of all respective parties. Only
      then can a well-defined SOC be established, thus improving the treatment of
      surgical patients for whom neuromonitoring is required.

PMID- 21102292
TI  - Management of severe spinal deformity: scoliosis and kyphosis.
AB  - STUDY DESIGN: Review of the literature and author';s experience with the
      treatment of severe spinal deformity. OBJECTIVE: To define the anatomic and
      physiologic challenges in treating severe spinal deformity and to describe the
      preoperative, intraoperative, and postoperative strategies to achieve the optimal
      safe result. SUMMARY OF BACKGROUND DATA: Severe pediatric spinal deformity is a
      relatively uncommon condition that often arises following treatment of early
      onset scoliosis. Patients most often present with severe clinical and
      radiographic deformity with poor pulmonary function. In contrast to the more
      common adolescent idiopathic scoliosis which is a primary spinal deformity,
      patients with severe spine deformity have the added chest wall deformity which
      may need to be addressed at the time of treatment. Previous literature has
      identified the challenges in the treatment of these patients and the higher risk
      for complications. METHODS: A literature review and review of the author's
      personal experience in the treatment of these patients was performed. An
      assessment of the preoperative, intraoperative, and postoperative factors leading
      to an optimal result was analyzed and reported. RESULTS: The early evaluation
      should include a multidisciplinary approach from the orthopaedic surgeon,
      pulmonologist, anesthesiologist, and perhaps the neurologist to provide a
      baseline assessment. Advanced imaging of the spine with computed tomography is
      useful especially when previous surgery has been performed and/or when plain
      radiography is limited. Magnetic resonance imaging of the spinal cord and brain
      stem is important to ensure that no neural axis abnormalities are present and can
      determine if spinal cord compression is present. Severe spinal deformity should
      be distinguished from the more common adolescent idiopathic scoliosis deformity
      in that both the spine and the chest wall are affected. Preoperative halo-gravity
      traction is an invaluable tool to improve the flexibility of the spine and chest,
      to improve pulmonary function, and to stress the spinal cord while the patient is
      awake and provides feedback as to the neurologic assessment. Surgical treatment
      should be divided into 3 phases. First, anchor placement which should be
      predominantly pedicle screws placed in a segmental fashion and also use of
      reduction screws when performing vertebral column resections. Second, steps
      should be performed to increase the flexibility of the spine and chest with
      incremental releases from simple posterior soft tissue releases to posterior
      facet resections, to vertebral column resections for the most severe deformity.
      The third phase is the correction of the spine and chest wall deformity. Many
      strategies can be used to correct these deformities and relies on good anchor
      point fixation and good releases of the spine and chest wall. Provisional rod
      fixation is critical when performing resection of the spine to allow for safe
      correction of the deformity. Improvements in the clinical and radiographic
      appearance, pulmonary function, and self image are often dramatic. CONCLUSION:
      The treatment of severe spinal deformity is challenging and requires careful
      assessment of the patient by the orthopaedic surgeon, anesthesiologist,
      pulmonologist, and neurologist especially when neurologic deficits are present.
      Proper planning and execution of the correct surgical procedure for the surgeon
      provides an outstanding life-changing result in these patients.

PMID- 21102293
TI  - Complications of growth-sparing surgery in early onset scoliosis.
AB  - STUDY DESIGN: Review of available literature, authors' opinion. OBJECTIVE: To
      describe complications associated with growth-sparing surgical treatment of early
      onset scoliosis (EOS). SUMMARY OF BACKGROUND DATA: EOS has many potential
      etiologies and is often associated with thoracic insufficiency syndrome. The
      growth of the spine, thorax, and lungs are interrelated, and severe EOS typically
      involves disturbance of the normal development of all 3. Severe EOS may be
      treated during growth with surgical techniques, intended to preserve growth while
      controlling deformity, the most common of which are spinal "growing rods" (GR) or
      "vertical expandable prosthetic titanium rib" (VEPTR). Although presently
      popular, there is minimal long-term data on the outcome of growth-sparing
      surgical techniques on EOS. METHODS: Review. RESULTS: Potential adverse outcomes
      of GR or VEPTR treatment of EOS include failure to prevent progressive deformity
      or thoracic insufficiency syndrome, an unacceptably short or stiff spine or
      deformed thorax, increased family burden of care, and potentially negative
      psychological consequences from repeated surgical interventions. Neither
      technique reliably controls all deformity over the entirety of growth period.
      Infections are common to both GR and VEPTR. Rod breakage and spontaneous
      premature spinal fusion beneath rods are troublesome complications in GR, whereas
      drift of rib attachments and chest wall scarring are anticipated complications in
      VEPTR treatment. Indications for GR and VEPTR overlap, but thoracogenic scoliosis
      and severe upper thoracic kyphosis are best treated by VEPTR and GR,
      respectively. CONCLUSION: Surgeons planning treatment of EOS should anticipate
      the many complications common to growth-sparing surgery, share their knowledge
      with families, and use complications as one factor in the complex decision as to
      when and whether to initiate the repetitive surgeries associated with GR or VEPTR
      in the treatment of severe EOS.

PMID- 21102294
TI  - Pediatric revision spinal deformity surgery: issues and complications.
AB  - STUDY DESIGN: A review of issues and concerns associated with pediatric revision
      surgery. OBJECTIVES: To describe: (1) the incidence, causes, and prevention of
      spine revision surgery in the pediatric population; and (2) the preoperative
      planning and imaging necessary for such surgeries and the associated
      intraoperative and technical complications (e.g., infection, blood loss, and
      incomplete deformity correction). SUMMARY OF BACKGROUND DATA: Revision surgery
      may be needed for pediatric spinal deformity because of many factors. This
      article describes the assessment and performance of revision surgery to optimize
      results. METHODS: The literature and the author's personal experience were
      reviewed. RESULTS: Rates of reoperation range from 4% to 25% for adolescent
      idiopathic scoliosis and are higher for neuromuscular or syndromic diagnoses. The
      most common indications for revision are infection, increased deformity, late
      operative site pain, pseudarthrosis, and implant dislodgement. Because revision
      cases are unique, preoperative planning should include a review of previous
      records and imaging for a thorough understanding of the bony and neurologic
      anatomy and instrumentation. Preoperative discussion with colleagues may help
      prevent the need for additional revision. Measures to minimize blood loss should
      be taken. Deformity correction may include mobilization by multiple osteotomies
      for long sweeping curves, or focal osteotomies (e.g., vertebral column resection
      or pedicle subtraction osteotomies) for focal deformity. If fusing additional
      levels, instrumentation should have adequate fixation and should connect to
      existing anchors so that the corrective force can be applied to the site of
      deformity. The possibility of occult infection should be considered; in the event
      of a late deep infection, options include removing implants and debriding the
      spine. However, there is a risk of increased deformity in the coronal and
      sagittal planes after implant removal. Because revision surgery itself may have a
      higher subsequent reoperation rate, thorough preparation should be done to ensure
      success. CONCLUSION: Cases of spine revision surgery in the pediatric population
      are best undertaken by an experienced surgeon and should involve thorough
      preoperative planning, proper equipment, and skilled assistance.

PMID- 21102295
TI  - Anticipating complications in pediatric deformity surgery: is any preparation
      necessary in healthy children?
AB  - STUDY DESIGN: Review article. OBJECTIVE: The goal of this review article is to
      discuss the steps taken to minimize and reduce complications from surgery in
      children and adolescents with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: A
      majority of children and adolescents with idiopathic scoliosis are otherwise
      healthy. Most lead relatively normal active lives. Assessing the functional
      impact of surgery is difficult due to the fact that most patients function at a
      high level before surgery. Surgery is geared to prevent the long-term problems
      associated with scoliosis. Complications do occur in the treatment of idiopathic
      scoliosis. Understanding the nature of these complications may help to improve
      long-term outcome. METHODS: Children and adolescents with idiopathic scoliosis
      were assessed using radiographs, magnetic resonance imaging, computed tomography
      scans, pain assessment, pulmonary assessment, surgical notes, history, and
      physical examinations. RESULTS: No true agreement exists in the literature for
      standard preoperative assessment of idiopathic scoliosis to reduce and prevent
      adverse events and surgical complications. CONCLUSION: The treating surgeon must
      be aware of the potential risks, adverse events, and complications associated
      with the procedure, and must be able to convey this to the patient and their
      family in a clear and concise manner.

PMID- 21102296
TI  - Complications in spinal deformity surgery: issues unrelated directly to
      intraoperative technical skills.
AB  - STUDY DESIGN: Literature review of complications unrelated directly to surgical
      skills involved in spinal deformity surgery. OBJECTIVE: Highlight complications
      associated with perioperative issues. SUMMARY OF BACKGROUND DATA: Complications
      can arise from mundane events that arise during the operative experience, but are
      not directly related to surgical skills. METHODS: Literature reviews that touches
      on the more common potential complication events that do not involve direct
      surgical expertise. RESULTS: The topics of positioning, nutrition, blood loss,
      comorbidities, OR time, and pulmonary and GI concerns are discussed as basics
      that could derail a surgical outcome even with an otherwise uneventful surgical
      technique. The need for vigilance is stressed and the nuances of understanding
      these are discussed. CONCLUSION: Mundane events can derail a perfectly executed
      surgical undertaking. Attention to detail, team work, close monitoring, and
      checklist type focus will help to improve, focus, and avoid these preventable
      complications that have nothing to do with direct surgical skills.

PMID- 21102297
TI  - Adult spinal deformity-postoperative standing imbalance: how much can you
      tolerate? An overview of key parameters in assessing alignment and planning
      corrective surgery.
AB  - STUDY DESIGN: Current concepts review. OBJECTIVE: Outline the basic principles in
      the evaluation and treatment of adult spinal deformity patients with a focus on
      goals to achieve during surgical realignment surgery. SUMMARY OF BACKGROUND DATA:
      Proper global alignment of the spine is critical in maintaining standing posture
      and balance in an efficient and pain-free manner. Outcomes data demonstrate the
      clinical effect of spinopelvic malalignment and form a basis for realignment
      strategies. METHODS: Correlation between certain radiographic parameters and
      patient self-reported pain and disability has been established. Using normative
      values for several important spinopelvic parameters (including sagittal vertical
      axis, pelvic tilt, and lumbar lordosis), spinopelvic radiographic realignment
      objectives were identified as a tool for clinical application. Because of the
      complex relationship between the spine and the pelvis in maintaining posture and
      the wide range of "normal" values for the associated parameters, a focus on
      global alignment, with proportionality of individual parameters to each other,
      was pursued to provide clinical relevance to planning realignment for deformity
      across a range of clinical cases. CONCLUSION: Good clinical outcome requires
      achieving proper spinopelvic alignment in the treatment of adult spinal
      deformity. Although variations in pelvic morphology exist, a framework has been
      established to determine ideal values for regional and global parameter in an
      individualized patient approach. When planning realignment surgery for adult
      spinal deformity, restoring low sagittal vertical axis and pelvic tilt values are
      critical goals, and should be combined with proportional lumbar lordosis to
      pelvic incidence.

PMID- 21102298
TI  - Standardizing care for high-risk patients in spine surgery: the Northwestern high
      risk spine protocol.
AB  - STUDY DESIGN: Review article of current literature on the preoperative evaluation
      and postoperative management of patients undergoing high-risk spine operations
      and a presentation of a multidisciplinary protocol for patients undergoing high
      risk spine operation. OBJECTIVE: To provide evidence-based outline of modifiable
      risk factors and give an example of a multidisciplinary protocol with the goal of
      improving outcomes. SUMMARY OF BACKGROUND DATA: Protocol-based care has been
      shown to improve outcomes in many areas of medicine. A protocol to evaluate
      patients undergoing high-risk procedures may ultimately improve patient outcomes.
      METHODS: The English language literature to date was reviewed on modifiable risk
      factors for spine surgery. A multidisciplinary team including hospitalists,
      critical care physicians, anesthesiologists, and spine surgeons from neurosurgery
      and orthopedics established an institutional protocol to provide comprehensive
      care in the pre-, peri-, and postoperative periods for patients undergoing high
      risk spine operations. RESULTS: An example of a comprehensive pre-, peri-, and
      postoperative high-risk spine protocol is provided, with focus on the
      preoperative assessment of patients undergoing high-risk spine operations and
      modifiable risk factors. CONCLUSION: Standardizing preoperative risk assessment
      may lead to better outcomes after major spine operations. A high-risk spine
      protocol may help patients by having dedicated physicians in multiple specialties
      focusing on all aspects of a patients care in the pre-, intra-, and postoperative
      phases.

PMID- 21102299
TI  - Preoperative medical and surgical planning for early onset scoliosis.
AB  - STUDY DESIGN: A review of current medical and surgical preoperative planning
      knowledge and protocols for children with early-onset scoliosis (EOS; onset less
      than 5 years of age). OBJECTIVE: To describe the preoperative planning process to
      undertake safe and effective treatment for the EOS patient. SUMMARY OF BACKGROUND
      DATA: Children with EOS present with a myriad of medical and orthopedic
      conditions associated with their specific diagnosis, and frequently require
      intensive preoperative evaluation and nutritional, pulmonary, and other support
      to prepare them for safe and effective treatment of the spinal/chest wall
      deformity. Such patients are among the most difficult and complex to treat
      effectively. METHODS: A literature review of known conditions associated with
      EOS, and a summary of current surgical techniques to maintain deformity control
      while promoting spine and thoracic growth, was undertaken. Current
      recommendations for preoperative support and postoperative management of these
      complex patients are summarized, drawn from the experiences of the author and
      members of study groups focusing on EOS. RESULTS: Preoperative assessment of
      respiratory function, potential for respiratory failure, and determination of
      objective criteria to indicate surgical management (deformity progression, lack
      of growth of spine and/or thoracic volume, lack of weight gain) are weighed
      against the potential for development of thoracic insufficiency syndrome.
      Magnetic resonance imaging evaluation for neuraxis abnormalities is considered on
      the basis of diagnosis. Nutritional status, osteopenia, and airway management are
      evaluated to minimize postoperative complications. Current general
      recommendations for implants and constructs for specific deformities are
      reviewed. CONCLUSION: Thorough preoperative evaluation of EOS patients provides
      the surgeon with the knowledge to produce a sound surgical plan for this
      difficult and complex to treat patient population.

PMID- 21102300
TI  - Sacropelvic fixation: techniques and complications.
AB  - STUDY DESIGN: Literature-based topic review. OBJECTIVE: To review the indications
      and techniques for different sacropelvic fixation methods and to outline
      important associated complications. SUMMARY OF BACKGROUND DATA: Despite all the
      advances and new developments in spinal instrumentation techniques, fixation at
      the lumbosacral junction continues to be one of the important challenges to spine
      surgeons. The poor bone quality of the sacrum, the complex regional anatomy, and
      the tremendous biomechanical forces at the lumbosacral junction contribute to the
      high rates of instrumentation-related problems. Although many techniques for
      sacropelvic fixation have been attempted, only a few are still widely used
      because of the high rate of complications associated with some of those
      techniques. METHODS: Review of literature and expert opinion. CONCLUSION: There
      are many indications for sacropelvic fixation. Long fusions to the sacrum are the
      most common reasons for extending the instrumentation to the pelvis. Spinal
      surgeons performing complex spinal reconstruction should be familiar with the
      currently available techniques, including their potential risks and
      complications. Surgical treatment decisions should be based on an individual
      patient's anatomy and abnormalities, and on the surgeon's experience.

PMID- 21102301
TI  - Minimizing complications with single submuscular growing rods: a review of
      technique and results on 88 patients with minimum two-year follow-up.
AB  - STUDY DESIGN: Retrospective clinical and radiologic review of consecutive series
      of patients treated with single submuscular growing rods from a single center
      with a minimum of 2-year follow-up. OBJECTIVES: To describe the surgical
      technique and methods used to minimize complications and to report on the
      outcomes of a large consecutive series of patients treated with single
      submuscular growing rods for scoliosis in the immature spine from a single
      center. SUMMARY OF BACKGROUND DATA: Previous studies have reported on the safety
      and efficacy of single and dual growing-rod constructs; however, these studies
      have been of small patient numbers with varying results. METHODS: Between 1999
      and 2007, 88 patients underwent the insertion of a single, submuscular growing
      rod construct for scoliosis. A clinical and radiologic review of these 88
      consecutive patients with a minimum of 2-year follow-up was conducted. Diagnoses
      include idiopathic, neuromuscular, syndromic, and congenital. Data include Cobb
      angle measurements, T1-S1 heights, number, and frequency of lengthening as well
      as complications. RESULTS: The patients underwent single submuscular growing-rod
      insertion at an average age of 7.0 years. The mean follow-up period was 42
      months. Twenty-eight patients had a simultaneous apical fusion. Growing-rod
      lengthening was performed on an average at 9-month intervals. The average initial
      Cobb angle was 73 degrees  (range: 40-117) and improved to 44 degrees  (range: 9
      90) at final follow-up. T1-S1 height gain was 3.37 cm; this translates to 1.04 cm
      growth/yr. No significant difference was noted between those who had undergone
      apical fusion and those without. Complications noted in this series include 8
      incidences of superficial infection and 3 of deep infection, proximal junctional
      kyphosis in 2 patients requiring early fusion, 31 rod fractures, 10 cases of
      proximal anchor failure, and 6 distal anchor failures. Thirty patients within
      study group have reached definitive fusion. CONCLUSION: Favorable outcomes have
      been demonstrated in this large single-center series of growing-rod constructs
      used to treat scoliosis in the growing spine. Their safety and efficacy in
      controlling spinal deformity and allowing spinal growth along with an acceptable
      rate of complications would support the continued use of single growing-rod
      constructs as a scoliosis management option.

PMID- 21102303
TI  - Electrical injury: a long-term analysis with review of regional differences.
AB  - Due to its relatively small share among burn injuries, published data on
      electrical injuries remain scarce, and differ in patient collectives due to
      infrastructural differences. We have retrospectively analyzed records of 56
      patients who were admitted because of electrical injury to our burn center from
      1994 to 2008, compared results with the current literature, and focused our
      review on regional differences. Patients in our collective were predominantly
      young men (71%, n = 40/56) and those who resulted from work-related accidents
      (59%, n = 33/56). The mean total burn surface area was 26%. In all, 93% of
      patients needed at least 1 operation, with 43% of patients requiring at least 1
      surgical intervention during a follow-up hospital stay. The mean length-of-stay
      was 44 days. Two patients died, accounting for a mortality rate of 3.6%. When
      comparing high to low-voltage injuries, patients in the former group were
      significantly younger, had more operations, and required a longer length-of-stay.
      With respect to work-related high-voltage injuries, job-specific male
      predominance explains for the demographic distribution of admissions. Low-voltage
      injuries continue to have low mortality rates in this part of Europe, most likely
      as a result of established high security standards as well as access to emergency
      treatment with subsequent intensive and specialist surgical care.

PMID- 21102302
TI  - Younger age at HAART initiation is associated with more rapid growth
      reconstitution.
AB  - OBJECTIVES: Patterns of growth following highly active antiretroviral therapy
      (HAART) administration among children are not well defined. The objective of this
      study was to determine rates and predictors of growth reconstitution among
      children on HAART. METHODS: A study was conducted among HIV-1-infected children
      initiating HAART at an HIV treatment clinic in Kenya. Kaplan-Meier survival
      curves and Cox proportional hazards regression models compared catch-up growth (Z
      score >= 0) at 12 months post-HAART. Multivariate linear mixed-effects models
      determined rates and predictors of growth following HAART. RESULTS: One hundred
      and seventy-three HIV-1-infected children initiated HAART with a median age of
      4.7 years [interquartile range (IQR) 2.4, 7.0]. At baseline, children below 3
      years had lower weight-for-age (WAZ) and weight-for-height (WHZ) Z-scores than
      children 3-5 and 6-10 years (WAZ: P = 0.03; WHZ: P = 0.006). Adjusting for
      baseline growth, children below 3 years were two to three-fold more likely to
      attain population age-norms (Z-score = 0) than 6-10 years (WAZ: P = 0.055; WHZ: P
      = 0.005) at 12 months post-HAART. After adjustment, children below 3 years had
      higher increases in WAZ and WHZ following HAART than 6-10 years (WAZ: P = 0.006;
      WHZ: P = 0.005). Children at WHO stage at least 3 at baseline experienced more
      rapid WHZ reconstitution (P = 0.002). Food supplementation while on HAART was
      associated with increased monthly gains in weight indices (WAZ: P = 0.001; WHZ: P
      = 0.005), and multivitamins were associated with greater increases in height (P <
      0.01). CONCLUSION: Following HAART initiation, younger children had more rapid
      catch-up to the population-average weight of their peers than older children,
      demonstrating growth benefit of earlier HAART. In addition to HAART, food
      supplementation and multivitamins may also accelerate growth reconstitution.

PMID- 21102304
TI  - Perioperative complications in patients undergoing peripheral nerve surgery.
AB  - INTRODUCTION: With increasing indications for and volume of patients undergoing
      peripheral nerve surgery, it becomes imperative that complication rates are
      monitored. This study looks at complication rates in all types of peripheral
      nerve surgery, develops a complication classification system, and defines the
      most common variables associated with failures and complications. METHODS: All
      peripheral nerve procedures performed by the senior author during a consecutive 6
      year period were retrospectively reviewed. Complications occurring within the
      first 30 postoperative days were recorded and classified into minor,
      intermediate, or major. RESULTS: A total of 5219 procedures were performed on
      1819 patients in all areas of the body (head and neck, trunk, and upper and lower
      extremities). The total complication rate was 2.91%, with a minor complication
      rate of 2.47%, intermediate complication rate of 0.44%, and major complication
      rate of 0%. CONCLUSIONS: This study confirms that peripheral nerve surgery can be
      safely performed with a very low complication rate if patients are properly
      selected and the surgeon is appropriately trained. A classification system for
      complications after peripheral nerve surgery and the most common variables
      associated with failures and complications are presented.

PMID- 21102305
TI  - Repair of microtia with sculpted rib cartilage grafts in identical, mirror-image
      twins: a case study.
AB  - Congenital abnormalities more commonly occur in multiple births-which are on the
      rise because of assisted reproductive techniques and fertility-stimulating drugs.
      One-third of twins are identical, and mirror-imaging is not as rare as one might
      think. It usually goes unnoticed because the differences between them are so
      subtle-unless they have an obvious congenital deformity. The author presents such
      a case, in which mirror-image twins were each afflicted with unilateral microtia.
      His management and repair of their ear deformities is presented herein.

PMID- 21102306
TI  - Tips for successful microvascular abdominal flap breast reconstruction utilizing
      the "total rib preservation" technique for internal mammary vessel exposure.
AB  - INTRODUCTION: The internal mammary vessels (IMVs) are increasingly the recipients
      for free flap breast reconstruction (FFBR). Access traditionally entails removing
      a segment of the third costal cartilage. Despite excellent exposure, some authors
      have reported localized tenderness as well as a thoracic contour deformity. We
      introduced the "total rib preservation" technique for IMV exposure after specific
      request by a patient, and have used it for all subsequent reconstructions.
      METHODS: All patients who underwent FFBR with rib preservation by a single
      surgeon in the year beginning June 2008 were studied prospectively.
      Intraoperative measurements of the inter-rib space available for microvascular
      anastomosis were taken. Operative details and flap outcomes were compared with a
      cohort of earlier patients who underwent rib sacrifice. RESULTS: Over a 12-month
      period, 42 FFBRs in 37 patients (36 deep inferior epigastric perforator, five
      muscle-sparing transverse rectus abdominis myocutaneous, and one superficial
      inferior epigastric artery flap) were performed by a single operator. All flap
      transfers were successful. In the first 4 patients, the interspace between the
      third and fourth ribs was used; but for all subsequent patients the second and
      third rib interspace was used. The average distance between adjacent ribs was
      21.3 mm (range, 9-28 mm) and the vessel preparation time decreased from an
      average of 93 to 49 minutes (first and last 5 cases). There was no significant
      difference in mean ischemia time between the rib preservation and the rib
      sacrifice groups (104.4 vs. 103.6 minutes). CONCLUSIONS: The total rib
      preservation method of IMV exposure is a viable, reproducible, and reliable
      option for microvascular breast reconstruction. It does not increase warm
      ischemia, which suggests time taken for anastomosis is not affected by rib
      preservation. There is a learning curve and care has to be taken to avoid
      possible pitfalls. We recommend the use of a higher rib interspace than
      originally described because of the greater vessel calibre, superior vessel
      exposure, and therefore, easier anastomosis.

PMID- 21102307
TI  - Morphological analysis of the upper eyelid tarsus in Asians.
AB  - PURPOSE: The present study aims to evaluate morphologic variations of the upper
      tarsus in Asians. METHODS: Measurements of superior-inferior and medial-lateral
      lengths were performed on 54 embalmed cadavers. The superior-inferior length of
      the tarsus was measured at the central and lateral parts. On the basis of the
      measured values, shapes of the tarsi were evaluated and categorized. RESULTS: The
      tarsi were classified into 3 morphologic categories-the sickle, triangular, and
      trapezoid types. The upper margins of the sickle, triangular, and trapezoid type
      tarsi present round, triangular, and flat lines, respectively. Among the 54
      examined specimens, 29 (55.6%), 16 (29.6%), and 9 (16.7%) belonged to the sickle,
      triangular, and trapezoid groups, respectively. CONCLUSIONS: The upper eyelid
      tarsi present morphologic variations with the Asian population. In performing
      surgical correction of blepharoptosis or surgical production of double-folds,
      this individual variation should be taken into consideration.

PMID- 21102308
TI  - Painful pelvic constriction band syndrome: a case report.
AB  - Plastic Surgeons, by training, are familiar with constriction bands of the
      fingers and toes. The purpose of this report is to discuss the management of a
      rare constriction band syndrome that was almost circumferential at the level of
      the T12 dermatome, and is most appropriately considered a pelvic constriction
      band as it was below the umbilicus. The patient had constriction bands about the
      toes at birth, and was also noted to have a band circumferentially below the
      umbilicus, which did not cause any distress and was not treated. When the patient
      entered high school and began to lift weights, play football, and have a growth
      spurt of 2 inches, he began to experience pain below each costal margin and over
      the iliac crest bilaterally. His physical examination demonstrated pain in the
      region of the subcostal nerve and the lateral cutaneous branches of L2 as they
      crossed the iliac crest. By CAT scan, the band appeared to include the rectus
      fascia. The band was excised to a depth that included the external oblique fascia
      and preserved the anterior rectus sheath. Small branches of the subcostal nerves
      and the lateral branches of L2 were killed, and, where appropriate, they were
      implanted into the external oblique muscle. Closure was obtained by undermining,
      and a Z-plasty was not included. Healing was without complications and gave an
      improved appearance to the trunk. At 6 months after surgery, he had resumed
      college-level rugby and had no further pain related to the constriction band.

PMID- 21102309
TI  - Resurfacing partial nose defects with a retroauricular skin/cartilage free flap.
AB  - BACKGROUND: The retroauricular skin has always received much attention by plastic
      surgeons for use in nose reconstruction because of its rich vascularity.
      Anatomically, the skin of this area lies hidden behind the ear and is very
      similar to that of the face. More importantly, the retroauricular skin flap along
      with the cartilage can be used to repair defective cartilage of the nose. All
      these reasons make this area an ideal donor site for nose reconstruction. This
      article presents the surgical procedures for reconstruction of partial nasal
      defects with the use of retroauricular skin/cartilage free flaps. METHODS: Based
      on the anatomy and blood supply of the retroauricular region, a flap was designed
      and harvested with the retroauricular vessels as its pedicle. This flap was used
      to repair the partial nose defects in 10 patients, between the years 2002 and
      2008. Of these, 4 patients presented with unilateral ala defects; 2 with nasal
      tip defects; 2 with defects on the nasal tip and bilateral ala; 1 with unilateral
      ala and tip defect; and 1 with unilateral ala and lateral defect. The size of the
      defect ranged from 2.5 * 1.5 cm to 4.0 * 3.0 cm. The flap varied between 3.0 *
      2.0 cm and 4.5 * 3.5 cm. In all cases, the auricular cartilage of 1.5 * 1.0 cm to
      1.0 * 0.5 cm was taken along with the flap. The retroauricular vessels were
      anastomosed with the facial vessels. The donor site was covered with full
      thickness skin graft or local flap. RESULTS: No flap failure was recorded.
      Excellent morphologic reconstruction was obtained with these flaps with no
      sequela at the donor site in terms of form and function. Postoperatively, the
      blood supply to the flaps was fairly good in 8 cases, although there was vein
      congestion in 2 cases on the fourth day. However, the postoperative results of
      the 10 cases were satisfactory after treatment. CONCLUSION: The retroauricular
      skin-cartilage free flap is a good choice for partial nasal reconstruction,
      having the merits of a well-hidden donor site, good color match, and 1-stage
      operation for cartilage support and nose reconstruction.

PMID- 21102310
TI  - Nasal spreader grafts: a comparison of medpor to autologous tissue
      reconstruction.
AB  - Reconstruction of the damaged nasal vault is challenging. Limited available
      autologous tissue has lead surgeons to pursue alloplastic alternatives. A
      retrospective review comparing 18 patients who underwent secondary rhinoplasty
      with internal nasal valve reconstruction with spreader graft (SG) implants using
      either autologous tissue or high-density porous polyethylene (Medpor) was
      performed. All underwent bilateral SG reconstruction of the internal nasal valve
      with Medpor (10 cases) or autologous cartilage (8 cases). Mean follow-up was 26
      months for the autologous group and 29 months for the Medpor group. Functional
      performance and aesthetic results were identical. Complications were few: 1 case
      of unilateral infection in the Medpor group treated with partial excision, and 1
      case of erythema at the auricular donor site for the autologous tissue group. For
      patients who have exhausted autologous tissue options or are unwilling to
      tolerate potential donor-site morbidity, the Medpor SG is an appropriate option
      that allows for excellent aesthetic and functional results that remains stable
      over time.

PMID- 21102311
TI  - Predictors of stent fracture in patients treated with closed-cell design stents:
      sirolimus-eluting stent and its bare-metal counterpart, the BX velocity stent.
AB  - OBJECTIVE: The aim of this study was to evaluate the predictors of coronary stent
      fracture in patients treated with closed-cell design stents including the
      sirolimus-eluting stent (SES) and its bare-metal platform, Bx velocity stent
      (BVS). BACKGROUND: Various mechanical factors have been considered to be the
      predictors of stent fracture, especially in patients treated with SES. However,
      it is unknown whether SES is more prone to fracture compared with BVS. METHODS:
      We retrospectively analyzed 391 lesions treated with SES or BVS in 339 patients
      who underwent follow-up coronary angiography. RESULTS: A total of 30 stent
      fractures (7.7%) in 28 patients treated with 29 SES (96.7%) and one BVS (3.3%)
      was found. On univariate analyses, stent fracture was related to angulated
      lesions (>45 degrees ) during diastole, longer stent, larger number of stents per
      lesion (P<0.001), right coronary artery (RCA) placement (P=0.008), and SES
      (P=0.016). On multivariate analyses, however, angulated lesion (odds ratio: 6.73;
      95% confidence interval: 2.71-16.71; P<0.001) and RCA placement (odds ratio:
      2.82; 95% confidence interval: 1.03-7.72; P=0.044) served as independent
      predictors of stent fracture while SES (P=0.080) and total stent length (P=0.069)
      showed only trends that did not reach statistical significance. CONCLUSIONS: This
      study showed that fracture of SES or BVS with the same closed-cell design
      platform was related to angulated lesion and RCA placement, but SES itself was
      not an independent predictor of stent fracture.

PMID- 21102312
TI  - Cardioprotective effects of perioperative beta-blockade in vascular surgery
      patients: fact or fiction?
AB  - PURPOSE OF REVIEW: Perioperative beta-blockade remains a subject of debate. In
      this review, recent literature and current guidelines for perioperative beta
      blockade in vascular surgery patients are discussed. RECENT FINDINGS: Available
      evidence suggests that perioperative beta-blockade may be beneficial in reducing
      cardiac events. However, in a recent large study, the incidences of stroke and
      mortality were increased in patients on perioperative beta-blockers. Large
      systematic reviews failed to demonstrate a net beneficial effect of perioperative
      beta-blockers. The 2009 American and the European guidelines for perioperative
      beta-blockade in vascular surgery disagree on the available evidence but do
      recommend beta-blockade for several indications. Most recent, Wallace and
      colleagues published a large-sized retrospective study, reporting a beneficial
      effect of the adoption of a protocol for perioperative beta-blockade. SUMMARY:
      Perioperative beta-blockade reduces cardiac events, but at the expense of
      increased risk for mortality and stroke. The guidelines seem to be eager to
      follow positive outcome studies, without considering the effects of beta-blockade
      on other organ systems. Perhaps the main reason for the reported cardioprotective
      effects of perioperative beta-blocker therapy should be sought in failing
      preoperative beta-blocker prophylaxis (irrespective of surgery).

PMID- 21102313
TI  - The current status of off-pump coronary bypass surgery.
AB  - PURPOSE OF REVIEW: Coronary artery disease is the leading cause of the death in
      the Western world. Almost 500 000 coronary artery bypass (CABG) surgeries are
      performed in the USA annually. In the last 20 years, interest has increased in
      performing CABG without the use of cardiopulmonary bypass (CPB), to reduce
      postoperative complications associated with the use of CPB and aortic
      manipulation. Still, only about 20% of all CABG surgeries are performed off-pump
      and it is still debatable whether off-pump CABG has decreased postoperative
      morbidity and mortality compared to conventional CABG surgery. RECENT FINDINGS:
      Off-pump CABG is associated with less blood loss and need for transfusion, less
      postoperative atrial fibrillation, less stroke and probably less renal
      dysfunction. It is also associated with shorter postoperative intubation time and
      hospital length of stay. However, conventional CABG is associated with more
      complete revascularization and better graft patency rate. SUMMARY: Both off-pump
      and on-pump CABG have an excellent safety profile with very low morbidity and
      mortality. It seems that off-pump CABG is associated with reduced short-term
      postoperative morbidity; however, graft patency rate is higher and long-term
      mortality may be lower after on-pump CABG. Patient selection criteria and
      surgical skills are at least as important as the decision about the surgical
      technique.

PMID- 21102314
TI  - Update on anesthetic management for esophagectomy.
AB  - PURPOSE OF REVIEW: The article highlights the current important issues
      surrounding the anesthetic care of patients presenting for esophagectomy. RECENT
      FINDINGS: With the decline in mortality from esophagectomy in high-volume centers
      over the last 30 years, focus may now be on decreasing morbidity. Improving the
      blood supply of the esophageal anastomosis, methods to reduce the incidence of
      pulmonary complications and optimizing fluid management in these patients are
      areas in which anesthetic care may contribute. There are also the potential
      benefits of minimally invasive techniques, which are increasingly being utilized.
      SUMMARY: The incorporation of thoracic epidural analgesia, goal-directed fluid
      management therapy, protective ventilation during one-lung anesthesia and
      strategies to improve perfusion of the gastric graft are some aspects which
      anesthetic care may impact.

PMID- 21102315
TI  - Sinus node revisited.
AB  - PURPOSE OF REVIEW: Sinus node disease (SND) is a common clinical condition and is
      the most common indication for permanent pacemaker implantation. This review aims
      to revisit the complex sinus node anatomy, the evolving understanding of its
      pacemaking mechanisms, the atrial myopathy in SND and sinus node remodeling.
      RECENT FINDINGS: Recent high-density noncontact mapping of the human sinus node
      showed multiple origins of sinus activation and exit sites with preferential
      pathways of conduction. Perhaps, a newly described discrete paranodal area
      containing a molecular mixture of nodal and atrial cells may account for this
      long recognized discrepancy between the anatomical and functional sinus node. The
      funny current (I(f)) driven 'membrane clock' is not solely responsible for sinus
      node automaticity, following recent recognition of the importance of the 'calcium
      clock'. Several molecular links to sinus node remodeling have recently been
      identified: loss of connexin-43 expression and down-regulation of I(ca,L) in
      aging; reduced I(f) and down-regulation of I(f) encoding HCN4 and HCN2 subunits
      in heart failure; and calcium clock malfunction with down-regulated HCN4, HCN2
      and minK in atrial fibrillation. SUMMARY: Ongoing research with improved
      technology and techniques continues to unravel new understandings and challenges
      to the century old discovery of the anatomical sinus node.

PMID- 21102316
TI  - Managing gastric residual volumes in the critically ill patient: an update.
AB  - PURPOSE OF REVIEW: Gastric residual volumes (GRVs) remain a major deterrent to
      adequately feeding patients with gastric-delivered enteral nutrition. The purpose
      of this review was to define the most up-to-date consensus of the utility of the
      use of GRVs for monitoring tube-feeding intolerance in gastric-fed patients.
      RECENT FINDINGS: The paper summarizes the pathophysiology of gastroparesis, the
      techniques for measuring GRVs, the significance of a large GRV, other factors to
      consider when measuring GRVs, the correlation between GRVs and aspiration
      pneumonia, national guideline statements on GRVs, the use of prokinetic agents in
      the treatment of high GRVs and the clinical impact of tolerating larger GRVs. The
      utility of GRVs for prevention of aspiration events with tube feeding has been
      brought into question. SUMMARY: Large GRVs usually result from some impediment in
      gastrointestinal motility (e.g. gastroparesis). There are numerous methods for
      measuring GRVs, most of which have not been standardized. It appears that there
      is little correlation between large GRVs and the development of aspiration
      pneumonia when tube feeding patients. Prokinetic agents have an inconsistent
      effect on the GRV size. US guidelines state that GRVs of less than 500 ml should
      not result in termination of enteral feeding. Allowing larger GRVs will allow
      patients to receive more calories when gastric fed without a deleterious clinical
      impact. The use of GRVs as a marker of feeding tolerance is of questionable
      utility.

PMID- 21102317
TI  - Refeeding in the ICU: an adult and pediatric problem.
AB  - PURPOSE OF REVIEW: To describe the etiology and complications of the refeeding
      syndrome. RECENT FINDINGS: Complications of the refeeding syndrome can include
      electrolyte abnormalities, heart failure, respiratory failure, and death. This
      syndrome is of particular importance to critically ill patients, who can be moved
      from the starved state to the fed state rapidly via enteral or parenteral
      nutrition. There are a variety of risk factors for the development of the
      refeeding syndrome. All of these risk factors are tied together by starvation
      physiology. Case reports and case series continue to be reported, suggesting that
      this entity continues to exist in critically ill patients. Initiation of enteral
      nutrition to patients with starvation physiology should be gradual and careful
      monitoring of electrolytes and organ function is critical during the early stages
      of refeeding. SUMMARY: The refeeding syndrome remains a significant issue in
      critically ill patients. Knowledge of the risk factors and the clinical signs of
      the refeeding syndrome is important to optimize outcomes.

PMID- 21102318
TI  - Vitamin D, neurocognitive functioning and immunocompetence.
AB  - PURPOSE OF REVIEW: Vitamin D deficiency is recognized as one of the most common
      medical conditions in children and adults. The major causes are inadequate sun
      exposure and inadequate intakes of dietary and supplemental vitamin D. Vitamin D
      deficiency and insufficiency defined as a 25-hydroxyvitamin D level less than 20
      and 21-29 ng/ml, respectively, have been linked to increased risk for a variety
      of medical conditions including cancer, heart disease, type II diabetes,
      infectious diseases, autoimmune diseases, metabolic bone diseases and
      neurological disorders. RECENT FINDINGS: The skeletal muscle and brain have a
      vitamin D receptor and the central nervous system has a capacity to activate
      vitamin D. Low vitamin D status has been linked to poor performance in
      neurocognitive testing in elderly. Vitamin D deficiency has been associated with
      muscle weakness, depression, schizophrenia, Alzheimer's disease, multiple
      sclerosis and a lower motor neuron-induced muscle atrophy. SUMMARY: Correcting
      vitamin D deficiency and preventing vitamin D deficiency in children and adults
      should be a high priority for healthcare professionals to reduce risk for a wide
      variety of neurological disorders. Children and adults should take at least 400
      international unit IU and 2000 IU vitamin D/day, respectively, to prevent vitamin
      D deficiency and insufficiency.

PMID- 21102319
TI  - The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic
      regulation.
AB  - PURPOSE OF REVIEW: The vertebrate cap'n'collar family transcription factor Nrf2
      and its invertebrate homologues SKN-1 (in worms) and CncC (in flies) function as
      master mediators of antioxidant and detoxification responses and regulators of
      the cellular redox state. Nrf2 controls gene expression programs that defend
      various tissues against diverse electrophilic stressors and oxidative insults,
      thus protecting the organism from disorders that are caused or exacerbated by
      such stresses. Moreover, studies on model organisms implicate the Nrf2 pathway in
      the prevention of aging-related diseases and suggest that SKN-1-regulated and
      CncC-regulated gene expression can promote longevity. These facets of Nrf2
      signaling have been thoroughly reviewed. This article discusses another aspect of
      the Nrf2 pathway's function that has not yet received the same degree of
      attention, but emerges as a topic of increasing interest and potential clinical
      impact: its role in metabolic regulation and its interaction with central
      signaling systems that respond to nutritional inputs. RECENT FINDINGS: Recent
      evidence identifies Nrf2 signaling as a mediator of the salutary effects of
      caloric restriction. Nrf2 signaling also crosstalks with metabolic signaling
      systems such as the insulin/Akt pathway as well as with the metabolism of lipids.
      Moreover, Nrf2 has a protective role in models of diabetic nephropathy. SUMMARY:
      The emerging role of Nrf2 as an effector of metabolic and longevity signals
      offers new therapeutic perspectives. The potential impact of pharmacological
      manipulation of Nrf2 signaling as a strategy for the prevention and treatment of
      metabolic disease can be envisioned.

PMID- 21102321
TI  - The accrual of bone mass during childhood and puberty.
AB  - PURPOSE OF REVIEW: To assess factors that influence the tempo of bone mass
      accrual with emphasis on obesity, exercise, and nutritional factors. RECENT
      FINDINGS: The prevalence of childhood obesity has increased dramatically
      throughout the world. Recent studies suggest that adiposity may be detrimental to
      development of bone strength parameters, and bone mass accrual during growth.
      Weight-bearing exercise during prepubertal and peripubertal period appears to
      enhance bone strength parameters. Maternal ultraviolet B radiation exposure and
      vitamin D status has been shown to have a positive effect on neonatal bone
      status, which appears to track up to the prepubertal period. Administration of
      vitamin D with or without calcium, but not calcium alone, during the prepubertal
      period might be an important 'window' for improving skeletal mineralization.
      SUMMARY: Obesity in children appears to be detrimental to development of bone
      strength parameters and bone mass accrual. Weight-bearing exercise during
      prepubertal and peripubertal period and vitamin D supplementation during
      pregnancy, infancy, and peripubertal period might be important for bone mass
      accrual. However, adequately powered randomized controlled trials with follow-up
      into adulthood are needed to determine if these interventions improve the tempo
      of bone mass accrual.

PMID- 21102320
TI  - Telomeres, lifestyle, cancer, and aging.
AB  - PURPOSE OF REVIEW: There has been growing evidence that lifestyle factors may
      affect the health and lifespan of an individual by affecting telomere length. The
      purpose of this review was to highlight the importance of telomeres in human
      health and aging and to summarize possible lifestyle factors that may affect
      health and longevity by altering the rate of telomere shortening. RECENT
      FINDINGS: Recent studies indicate that telomere length, which can be affected by
      various lifestyle factors, can affect the pace of aging and onset of age
      associated diseases. SUMMARY: Telomere length shortens with age. Progressive
      shortening of telomeres leads to senescence, apoptosis, or oncogenic
      transformation of somatic cells, affecting the health and lifespan of an
      individual. Shorter telomeres have been associated with increased incidence of
      diseases and poor survival. The rate of telomere shortening can be either
      increased or decreased by specific lifestyle factors. Better choice of diet and
      activities has great potential to reduce the rate of telomere shortening or at
      least prevent excessive telomere attrition, leading to delayed onset of age
      associated diseases and increased lifespan. This review highlights the role of
      telomeres in aging and describes the lifestyle factors which may affect
      telomeres, human health, and aging.

PMID- 21102322
TI  - Transmembrane guanylate cyclase in intestinal pathophysiology.
AB  - PURPOSE OF REVIEW: Production of cyclic guanosine monophosphate (cGMP) by
      guanylate cyclase is of critical importance to gastrointestinal physiology. Tight
      regulation of cGMP concentration is necessary for proper intestinal secretion and
      intestinal epithelial cell proliferative and apoptotic homeostasis. This review
      focuses on recent work detailing the role of a subset of transmembrane guanylate
      cyclases in the pathophysiology of intestinal secretory and motility disorders
      and intestinal epithelial cell transformation. Also considered is the potential
      for therapeutic manipulation of intestinal guanylate cyclase/cGMP signaling for
      the correction of chronic constipation and gastrointestinal cancer. RECENT
      FINDINGS: Recent work in mice and humans suggests a role for transmembrane
      guanylate cyclases in intestinal fluid secretion as well as hormonal enteric
      renal signaling which mediates postprandial natriuresis. Transmembrane guanylate
      cyclases are also important in gastrointestinal transit rate and motility.
      Ongoing clinical trials have found that guanylate cyclase activating peptides are
      safe and effective in the treatment of constipation-predominant irritable bowel
      syndrome and chronic constipation. In addition, accumulating evidence indicates
      that membrane-associated guanylate cyclase receptors regulate intestinal
      epithelial cell homeostatic proliferation and apoptosis as well as
      gastrointestinal malignancy. The anticancer activity of cGMP signaling in animal
      studies suggests additional therapeutic applications for guanylate cyclase
      agonists. SUMMARY: Progress toward understanding gastrointestinal transmembrane
      guanylate cyclase/cGMP physiology has recently accelerated due to definitive in
      vitro studies and work using gene-targeted animal models and has facilitated the
      development of safe and effective drugs designed to regulate cGMP production in
      the intestine. Current work should be directed toward a detailed understanding of
      cGMP effector pathways and the manner in which subcellular concentrations of cGMP
      regulate them to influence intestinal health and disease.

PMID- 21102323
TI  - Small intestine and microbiota.
AB  - PURPOSE OF REVIEW: To highlight the recent studies which have enhanced our
      appreciation of the composition of the microbiota in the human small intestine
      and its relevance to the health of the host. RECENT FINDINGS: In the past number
      of years, the composition of the microorganisms present in our small intestines
      has been the subject of greater scrutiny than ever before. These investigations
      have been possible as a consequence of the development and utilization of new
      molecular tools which have revolutionized the field of microbial ecology and have
      focused predominantly on the small intestinal microbiota associated with
      pediatric celiac disease, inflammatory bowel disease, irritable bowel syndrome
      and pouchitis. The impact of invasive procedures, such as small bowel transplant,
      ileostomy and ileal pouch anal anastomosis, on the ileal microbiota has also been
      investigated. SUMMARY: The ever greater appreciation of the link between the
      small intestinal microbiota and the health status of the host has the potential
      to lead to the development of new strategies to alter this microbiota in a
      targeted way to prevent or treat specific disorders.

PMID- 21102324
TI  - Neutropenia associated with rituximab therapy.
AB  - PURPOSE OF REVIEW: Several recent studies have reported the occurrence of late
      onset neutropenia (LON) following the use of rituximab or rituximab-based
      therapies. While this phenomenon is typically self-limiting and of no clinical
      significance, recognizing its existence is important given the expanding use of
      rituximab in both hematologic and nonhematologic disorders. This review discusses
      the incidence of LON and explores several hypotheses that have been proposed to
      explain its occurrence. RECENT FINDINGS: While the etiology of LON is uncertain
      and poorly understood, mechanisms that have been suggested include the production
      of antineutrophil antibodies following rituximab, the expansion of large granular
      lymphocyte (LGL) populations that may induce neutrophil apoptosis through Fas and
      Fas-ligand interactions, and aberrant B-cell reconstitution following rituximab
      leading to immune dyscrasias and the development of neutropenia. We explored an
      alternative hypothesis that LON following rituximab is caused by perturbations of
      granulocyte homeostasis, mediated by a complex interaction between B-cell
      recovery and the chemokine stromal-derived factor-1 (SDF-1). SUMMARY: While
      rituximab has been associated with both early and late neutropenia, LON occurring
      several weeks to several months after the administration of rituximab is a
      distinct biologic phenomenon that appears to be related to B-cell recovery.
      Though it occurs frequently, it is a self-limiting process and is rarely
      associated with significant clinical sequelae.

PMID- 21102325
TI  - Neutrophil gelatinase-associated lipocalin as a marker of acute renal disease.
AB  - PURPOSE OF REVIEW: Acute renal disease has major prognostic impact in
      hospitalized patients. Early diagnosis using renal function markers such as serum
      creatinine or urinary output and effective treatment are currently not possible.
      This review focuses on recent studies examining the biological characteristics
      and the diagnostic and prognostic value of a novel biomarker, neutrophil
      gelatinase-associated lipocalin (NGAL), in patients at risk for acute renal
      disease. RECENT FINDINGS: NGAL levels increase early and proportional to the
      degree of renal injury in the urine and plasma. Here, we report the results of
      clinical studies where NGAL was measured in 325 patients with autoimmune and
      infectious diseases, those with cisplatin-associated nephrotoxicity, and more
      than 4000 patients at risk of acute kidney injury due to sepsis, cardiac surgery,
      exposure to contrast media, or after renal transplantation. Whenever renal damage
      occurred, as evidenced by histopathology or subsequent increase in serum
      creatinine levels, NGAL levels were higher than in patients without acute renal
      disease. An increase in NGAL substantially preceded clinical diagnosis of acute
      renal disease. SUMMARY: NGAL fulfills many characteristics of an appropriate
      'real-time' renal biomarker. The data on NGAL could justify re-assessment of the
      concept and definition of acute kidney injury.

PMID- 21102327
TI  - Dietary protein and skeletal health: a review of recent human research.
AB  - PURPOSE OF REVIEW: Both dietary calcium and vitamin D are undoubtedly beneficial
      to skeletal health. In contrast, despite intense investigation, the impact of
      dietary protein on calcium metabolism and bone balance remains controversial. A
      widely held view is that high intakes of animal protein result in increased bone
      resorption, reduced bone mineral density, and increased fractures because of its
      ability to generate a high fixed metabolic acid load. The purpose of this review
      is to present the recent or most important epidemiological and clinical trials in
      humans that evaluated dietary protein's impact on skeletal health. RECENT
      FINDINGS: Many epidemiological studies have found a significant positive
      relationship between protein intake and bone mass or density. Similarly, isotopic
      studies in humans have also demonstrated greater calcium retention and absorption
      by individuals consuming high-protein diets, particularly when the calcium
      content of the diet was limiting. High-protein intake may positively impact bone
      health by several mechanisms, including calcium absorption, stimulation of the
      secretion of insulin-like growth factor-1, and enhancement of lean body mass. The
      concept that an increase in dietary protein induces a large enough shift in
      systemic pH to increase osteoclastic bone resorption seems untenable. SUMMARY:
      Recent epidemiological, isotopic and meta-analysis studies suggest that dietary
      protein works synergistically with calcium to improve calcium retention and bone
      metabolism. The recommendation to intentionally restrict dietary protein to
      improve bone health is unwarranted, and potentially even dangerous to those
      individuals who consume inadequate protein.

PMID- 21102328
TI  - Nitrite and nitrate: cardiovascular risk-benefit and metabolic effect.
AB  - PURPOSE OF REVIEW: To review the most recent published literature on the
      biological effects of nitrite and nitrate in order to establish the context for
      potential health benefits vs. potential risks or adverse effects. Nitrite and
      nitrate are indigenous to our diet and are formed naturally within our body from
      the oxidation of nitric oxide. Emerging health benefits from dietary sources of
      nitrite and nitrate contradict decades of epidemiological research that have
      suggested an association of nitrite and nitrate in foods, primarily cured and
      processed meat, with certain cancers. RECENT FINDINGS: The major source of
      exposure of nitrite and nitrate comes from the consumption of nitrate-enriched
      vegetables. The preponderance of epidemiological studies shows a very weak
      association with consumption of meats and certain cancers, which contain very
      little nitrite and nitrate. Nitrite and nitrate in certain foods and diets can be
      metabolized to nitric oxide and promote cardiovascular benefits and
      cytoprotection. SUMMARY: The cardiovascular benefits of nitrite and nitrate are
      beginning to be translated in humans by the increasing number of clinical trials
      using nitrite and nitrate. The collective body of evidence suggests that foods
      enriched in nitrite and nitrate provide significant health benefits with very
      little risk.

PMID- 21102326
TI  - Role of fibrates in cardiovascular disease prevention, the ACCORD-Lipid
      perspective.
AB  - PURPOSE OF REVIEW: To examine the results of the Action to Control Cardiovascular
      Risk in Diabetes (ACCORD)-Lipid trial, particularly the subgroup analyses. It is
      important, when a study fails to meet its overall primary endpoint, to ensure
      that interpretation of the results include analyses of subgroups that might
      benefit from the treatment tested. The goal of this review, therefore, is to
      provide insight and advice to physicians and healthcare workers treating patients
      similar to those enrolled in ACCORD. RECENT FINDINGS: The recently published
      results of ACCORD-Lipid trial will be presented upon the background of previous
      trials that have tested the ability of fibrates to lower cardiovascular risk.
      SUMMARY: Although ACCORD-Lipid trial did not provide support for the general
      addition of fenofibrate to statin-treated patients with type 2 diabetes mellitus
      (T2DM), it added significantly to the results from fibrate monotherapy trials
      indicative of benefit from such treatment in subgroups of patients who present
      with significant dyslipidemia. In particular, ACCORD-Lipid trial, in our view,
      supports the addition of fenofibrate to statin therapy in patients with T2DM and
      optimal low-density lipoprotein cholesterol levels but persistent, significant
      hypertriglyceridemia (>200 mg/dl) and low high-density lipoprotein cholesterol
      levels (<35-40 mg/dl).

PMID- 21102329
TI  - Getting personal: considering variable interindividual responsiveness to dietary
      lipid-lowering therapies.
AB  - PURPOSE OF REVIEW: There is substantial interindividual variation in the response
      of blood lipids to dietary therapies. The purpose of this review is to highlight
      recent developments in identifying patient-specific factors that contribute to
      the significant heterogeneity of responsiveness in lipids to dietary changes and
      consumption of dietary bioactive compounds. RECENT FINDINGS: Recent findings
      suggest that a variety of patient-specific physiological, pathological,
      environmental, and genetic factors influence the effectiveness of dietary lipid
      lowering therapies. SUMMARY: Although genetic markers of responsiveness will
      revolutionize future personalized nutrition therapies, current research
      priorities should emphasize the identification of readily accessible metabolic
      biomarkers of responsiveness in patient subgroups.

PMID- 21102330
TI  - Possible contributions of lipoproteins and cholesterol to the pathogenesis of
      diabetes mellitus type 2.
AB  - PURPOSE OF REVIEW: Low HDL cholesterol and hypertriglyceridemia as well as
      lowering of LDL cholesterol with statins increase the risk of T2DM. We discuss
      the recent findings on the effects of lipoproteins and cholesterol on the
      function and survival of pancreatic beta-cells as well as on obesity and insulin
      sensitivity of muscle and liver. RECENT FINDINGS: LDL inhibits glucose-stimulated
      insulin secretion and proliferation of beta-cells by LDL-receptor dependent and
      independent mechanisms, respectively. ApoA-I and HDL stimulate insulin secretion
      by interaction with ABCA1, ABCG1 or SR-BI and also inhibit apoptosis of beta
      cells. Mice with targeted knockouts of ABCA1 or ABCG1 in beta-cells show reduced
      insulin secretion and glucose tolerance. ABCG1 contributes to the enrichment of
      insulin secretory granules with cholesterol, which is needed for their formation
      and trafficking to the plasma membrane whereas ABCA1-mediated cholesterol efflux
      from the plasma membrane appears to be important for their subsequent exocytosis.
      In mice, overexpression of apoA-I decreases body fat accumulation and increases
      insulin sensitivity of muscle and liver by inducing the phosphorylation of AMP
      kinase. SUMMARY: LDL, HDL and cholesterol regulate the function and survival of
      beta-cells. HDL also exerts antiobesity and insulin-sensitizing effects. Thus
      dyslipidemias may not only be consequences but also contributors to the
      pathogenesis and hence targets for prevention of T2DM.

PMID- 21102331
TI  - Reperfusion therapy in acute cerebrovascular syndrome.
AB  - PURPOSE OF REVIEW: Modern reperfusion therapy in acute ischemic stroke therapy is
      based on an 'as fast as possible' recanalization approach to obtain favorable
      clinical outcomes. However, arterial recanalization may be achieved without
      favorable clinical outcome, raising the question of the target population to be
      treated. We outline key issues that underline acute revascularization therapies.
      RECENT FINDINGS: Intravenous (i.v.) thrombolysis remains the gold standard with
      the benefit of speed but lower recanalization rates of large artery occlusions as
      compared with intra-arterial routes. Conversely, intra-arterial therapies report
      higher recanalization rates, but are hampered by procedural delays and risks.
      Higher rates of recanalization in intra-arterial studies using clot-removal
      devices have not translated into improved patient functional outcome as compared
      with i.v. thrombolysis trials. Combined i.v.-intra-arterial therapy hold great
      promise with both the advantages of i.v. and intra-arterial routes. SUMMARY:
      Endovascular therapy is potentially superior to i.v. tissue-type plasminogen
      activator with the development of new devices, which are now available, but none
      has been evaluated vs. i.v. thrombolysis. Future developments may include
      combined strategies or a 'pure' mechanical approach. The critical issue is time
      to-reperfusion based on a brain imaging showing salvageable brain tissue with a
      reduced risk of adverse events associated with reperfusion. Current brain imaging
      techniques are probably not good enough to discriminate salvageable brain, and
      parenchymal lesion that may suffer from reperfusion injury.

PMID- 21102333
TI  - Vascular disorders in neuro-ophthalmology.
AB  - PURPOSE OF REVIEW: The aim is to briefly discuss the currently controversial
      management of nonarteritic anterior ischemic optic neuropathy (NA-AION) and
      central retinal artery occlusion (CRAO). RECENT FINDINGS: The role of systemic
      corticosteroid therapy and aspirin in NA-AION and of thrombolysis in CRAO is
      discussed. SUMMARY: NA-AION is a major cause of seriously impaired vision. A
      recent large prospective study has shown that systemic corticosteroid resulted in
      a significantly higher probability of improvement in visual acuity (P = 0.001)
      and visual fields (P = 0.005), compared to an untreated group. In CRAO, the
      latest prospective study has shown that thrombolytic therapy not only has no
      beneficial effect but also is harmful.

PMID- 21102332
TI  - Oscillopsia: causes and management.
AB  - PURPOSE OF REVIEW: Oscillopsia is an illusion of an unstable visual world. It is
      associated with poor visual acuity and is a disabling and distressing condition
      reported by numerous patients with neurological disorders. The goal of this study
      is to review the recent findings in the various pathophysiological mechanisms of
      oscillopsia and the potential treatments available. RECENT FINDINGS: Oscillopsia
      most often results from abnormal eye movements or from impaired vestibulo-ocular
      reflex. A special emphasis is provided on new hypotheses concerning the
      mechanisms of pendular nystagmus associated with oculopalatal tremor; on the
      clinical relevance of fixation instability in the diagnosis of degenerative
      disease; and on the causes of vestibular areflexia. Oscillopsia could also
      theoretically result from a deficit in mechanisms underpinning perceptual
      stability maintenance despite constant gaze displacement in the environment. The
      recent findings concerning the mechanisms and underlying neural network
      subserving this phenomenon of 'spatial constancy' are developed. SUMMARY:
      Oscillopsia may result either from impaired ocular stability or impaired
      compensation or suppression of afferent visual information resulting from normal
      eye movements. Understanding the exact mechanisms of oscillopsia may lead to
      novel treatment.

PMID- 21102334
TI  - Disorder of higher visual function.
AB  - PURPOSE OF REVIEW: Both monkey and human neuroimaging studies show that visual
      processing beyond the striate cortex involves a highly complex network of regions
      with modular functions. Lesions within this network lead to specific clinical
      syndromes. In this review we discuss studies on blindsight, which is the ability
      of remaining regions to support vision in the absence of striate cortex or visual
      awareness, recent work on 'ventral stream' syndromes such as object agnosia,
      alexia, prosopagnosia, and topographagnosia, which follow damage to medial
      occipitotemporal structures, and simultanagnosia, the classic 'dorsal stream'
      deficit related to bilateral occipitoparietal lesions. RECENT FINDINGS: We
      highlight work on the anatomic basis of blindsight, the recent description of the
      new disorder developmental topographic disorientation, and studies contrasting
      global and local perception in simultanagnosia. SUMMARY: These studies advance
      our understanding of the mechanisms of complex visual processing and provide an
      important neuropsychological complement to our expanding knowledge about vision
      from functional neuroimaging.

PMID- 21102335
TI  - Olfactory epithelial transplantation: possible mechanism for restoration of
      smell.
AB  - PURPOSE OF REVIEW: To discuss the unique properties of the olfactory epithelium
      and the potential use of olfactory epithelial grafts to restore olfactory
      function. RECENT FINDINGS: Sensory neurons in the olfactory epithelium undergo
      continuous regeneration, grow new axons, and reestablish connections with the
      olfactory bulb throughout life. When transplanted into different regions of the
      brain, olfactory epithelial graft cells retain their morphological and
      regenerative properties. Olfactory cells within the grafts grow axons that enter
      into the surrounding brain tissue. Recent studies have shown that the olfactory
      epithelium can be grafted directly to the olfactory bulb. SUMMARY: The olfactory
      epithelium has a remarkable capacity to continuously generate new sensory neurons
      and survives grafting into different regions of the brain. A review of the
      literature and the future use of olfactory grafts as a potential method to
      restore olfactory function is discussed.

PMID- 21102336
TI  - Sublingual immunotherapy for allergic rhinitis: an update.
AB  - PURPOSE OF REVIEW: Sublingual immunotherapy (SLIT) has progressively gained
      credibility. Randomized double-blind placebo-controlled trials, meta-analyses and
      mechanistic studies have accumulated rapidly in the last years. We will review
      herein a brief history of SLIT, its indications and the safety aspects and will
      discuss the main unmet needs and the points to be developed in the field. RECENT
      FINDINGS: During the last year, new information on SLIT has become available,
      mainly from the so-called big trials, and some important aspects have been
      partially clarified. In addition, the possible indications to SLIT began to be
      expanded. SUMMARY: The dose dependency of the efficacy of SLIT and the optimal
      maintenance dose have been identified at least for grass allergens. The safety is
      well demonstrated in both adults and children.

PMID- 21102337
TI  - Indications for the osteoplastic flap in the endoscopic era.
AB  - PURPOSE OF REVIEW: To review and highlight recent articles on the osteoplastic
      flap over the last 12 months. RECENT FINDINGS: Although advances in endoscopic
      sinus surgery have permitted rhinologists to manage a wide range of frontal sinus
      disease, recent retrospective studies have examined specific indications for the
      osteoplastic flap in this endoscopic era. Whether it will be inflammatory,
      anatomical or sinonasal tumor considerations, the osteoplastic flap remains an
      important surgical technique when endoscopic approaches are limited. SUMMARY: The
      osteoplastic flap will remain an important tool in the armamentarium of the
      endoscopic surgeon to provide comprehensive management of the frontal sinus.

PMID- 21102338
TI  - Possible association between a genetic polymorphism at 8q24 and risk of upper
      gastrointestinal cancer.
AB  - Over recent years, genome-wide association studies have contributed to our
      understanding of genetic susceptibility to sporadic cancer. In this study, we
      assessed the association between upper gastrointestinal cancer risk and four
      genome-wide association studies-identified single nucleotide polymorphisms
      (SNPs), implicated earlier in prostate and colorectal cancer susceptibility.
      Genotyping for each SNP was performed in two independent Caucasian population
      based case-control studies. The first study comprised 290 gastric cancer cases
      and 374 controls. The second study included 185 noncardia gastric cancers, 123
      cardia cancers, 158 oesophageal cancers and 209 controls. Odds ratios (ORs) were
      computed from logistic models and adjusted for potential confounding variables.
      An inverse association was observed between the SNP rs1447295, located at 8q24,
      and gastric cancer risk in the first study population (OR=0.63; 95% confidence
      interval: 0.41-0.97). A positive association was observed for the same SNP and
      oesophageal squamous cell carcinoma in the second study population (OR=7.43; 95%
      confidence interval: 1.37-49.98). No significant associations were detected in
      either study for the three remaining SNPs (rs6983297, rs10505477 and rs719725).
      Our data represent novel findings on heritable susceptibility to gastric and
      oesophageal cancer and warrant validation in additional populations.

PMID- 21102339
TI  - The changing epidemiology of colorectal cancer and its relevance for adapting
      screening guidelines and methods.
AB  - In many countries at risk for colorectal cancer (CRC), screening guidelines
      provide average-risk screening for patients aged between the ages of 50 and 75
      years. However, an earlier onset of CRC, an increasing life span and an incidence
      of right-sided CRC have been noted, which could require changes in age guidelines
      and screening methodology, especially for the elderly. We examined this in our
      Jewish populations using Israel Cancer Registry data, 1980-2008, computed by age
      groups, sex, ethnic groups, cancer site, and cancer stage. In patients who were
      below 50 years of age, there was no significant increase in incidence except for
      men born in Israel (P=0.05). In patients aged between 50 and 74 or more than 75
      years there was an increased incidence (P<0.001 for both). However, the
      percentage for CRC patients aged between 50 and 74 years decreased but those who
      were aged more than 75 years increased (P<0.001 for both). Therefore, 45.3% of
      patients (39.1% aged >= 75 years) would not be electively screened. In addition,
      there was an increased trend (P<0.001) for right-sided (from cecum to and
      including the splenic flexure) CRC in patients both 50-74 and more than 75 years
      old. During 1999-2008, as compared with patients aged between 50 and 74 years,
      those below 50 years were less likely to be diagnosed with stage 1 or 2 CRC and
      more likely have stage 3 or 4 CRC (P<0.01 for all), whereas those aged more than
      75 years were less likely to have stage 3 CRC (P<0.01). These results should
      influence CRC screening age guidelines, especially for 'healthy' individuals aged
      75 years or more, and their need for noninvasive, but sensitive and specific pre
      colonoscopy screening methodologies. In addition, the more advanced cancer stage
      in the patients aged below 50 years needs to make the treating physicians more
      aware of the fact that CRC can occur even at this age.

PMID- 21102340
TI  - Diagnostic assay of carcinoembryonic antigen tumor markers using a fluorine
      immobilized biosensor with handmade voltammetric circuit.
AB  - The tumor marker carcinoembryonic antigen (CEA) was investigated using a graphite
      pencil electrode (PE) and fluorine immobilized onto a graphite pencil carbon
      electrode (FPE). The optimum diagnostic conditions for square wave (SW) stripping
      voltammetry and cyclic voltammetry were searched. The voltammograms indicated
      three other detection ranges of 0.4-1.6 MUg/l cyclic voltammetry (PE) seven
      points, 0.2-1.2 MUg/l SW (PE) cathodic six points, and better sensitive ranges of
      0.05-0.45 MUg/l SW (FPE). These were obtained within a diagnostic accumulation
      time of 120 s in 0.1 mol/l ammonium phosphate electrolyte solution of pH 5.0.
      Under optimum SW conditions, the detection limit (S/N) approached 0.08 MUg/l CEA,
      and the relative standard deviation at 10 mg/l CEA was 0.074% in 15 measurements.
      The proposed method can be applied in tumor assay using cancer patient urine.

PMID- 21102341
TI  - Mammographic density as a risk factor for breast cancer in a German case-control
      study.
AB  - Mammographic percent density (MD) is recognized as one of the strongest risk
      factors associated with breast cancer. This matched case-control study
      investigated whether MD represents an independent risk factor. Mammograms were
      obtained from 1025 breast cancer patients and from 520 healthy controls. MD was
      measured using a quantitative computer-based threshold method (0-100%). Breast
      cancer patients had a higher MD than healthy controls (38 vs. 32%, P<0.01). MD
      was significantly higher in association with factors such as age over 60 years,
      body mass index (BMI) of 25-30 kg/m2, nulliparity or low parity (one to two
      births). Average MD was inversely associated with age, BMI, parity and positively
      associated with age at first full-term pregnancy. MD was higher in women with at
      least one first-degree relative affected, but only among patients and not in the
      group of healthy controls (P<0.01/P=0.61). In women with an MD of 25% or more,
      the risk of breast cancer was doubled compared with women with an MD of less than
      10% (odds ratio: 2.1; 95% confidence interval: 1.3-3.4; P<0.01); in the
      postmenopausal subgroup, the risk was nearly tripled (odds ratio: 2.7; 95%
      confidence interval: 1.6-4.7; P<0.001). This study provides further evidence that
      MD is an important risk factor for breast cancer. These results indicate strong
      associations between MD and the risk of breast cancer in a matched case-control
      study in Germany.

PMID- 21102342
TI  - Stable versus progressive hepatitis unique to pregnancy.
AB  - BACKGROUND: Urgent delivery of the fetus is often considered as the treatment of
      choice for mothers in their second or third trimester with hepatitis unique to
      pregnancy (HUP). OBJECTIVE: To determine whether standard liver function tests
      (serum bilirubin and international normalized ratio levels) help to identify
      mothers and their newborns who might benefit from early delivery. METHODS: A
      total of 149 patients with HUP were retrospectively classified as those with
      normal (stable-HUP, n=118) or abnormal (progressive-HUP, n=31) liver function
      tests. Clinical outcomes consisted of maternal lengths of hospital stay after
      delivery and neonatal appearance, pulse, grimace, activity, respiration score
      ratings at 0 and 5 min. RESULTS: Patients with stable-HUP had similar lengths of
      hospital stay after delivery whether delivered early (4.8+/-3.4 days) or at term
      (4.8+/-3.6 days). Appearance, pulse, grimace, activity, respiration score ratings
      at birth were similar in neonates from patients with stable-HUP delivered
      prematurely (5.8+/-2.7) and at term (7.8+/-1.7, P=0.48) but significantly higher
      at 5 min in those delivered at term (7.5+/-2.0 vs. 8.9+/-0.3, P=0.003). Too few
      patients with progressive-HUP were delivered at term (N=4) to allow similar
      comparisons in this cohort. CONCLUSION: The results of this study indicate that
      mothers with HUP and normal liver function tests (bilirubin and international
      normalized ratio) can be safely followed to term without jeopardizing the health
      of either mother or neonates. Additional studies are required to determine
      whether abnormal liver function tests represent an indication for immediate
      delivery of the fetus in mothers with HUP.

PMID- 21102343
TI  - A comparison of molecular and cytogenetic techniques for the diagnosis of
      pregnancy loss.
AB  - PURPOSE: To evaluate the sensitivity, specificity, advantages, and limitations of
      multiplex ligation-dependent probe amplification compared with conventional
      karyotype analysis in the investigation of contributing factors to recurrent
      pregnancy loss. METHOD: A cohort of 284 patients underwent side-by-side analysis
      of products of conception by both conventional karyotyping and multiplex ligation
      dependent probe amplification with direct comparison of results. RESULTS:
      Multiplex ligation-dependent probe amplification was shown to enable a diagnosis
      for an additional 47 (16.5%) patients compared with conventional karyotype
      analysis. However, this advantage was offset by some disadvantages of the method,
      including a high false-positive rate (8/104; 7.7%), as demonstrated by single-arm
      probe abnormalities of uncertain clinical significance, as well as the inability
      to characterize structural rearrangements, such as Robertsonian translocations,
      which comprised 2.46% of samples (99% confidence interval = 0.09-4.83), and
      ploidy changes. The calculated performance characteristics of multiplex ligation
      dependent probe amplification in this cohort yielded a sensitivity of 86.9% and
      specificity of 92.4%. CONCLUSIONS: The advantages of now widely accepted
      molecular methodologies, such as lower failure rates, faster turnaround times,
      and lower cost, must be complemented by adequate counseling, family follow-up,
      and specific diagnostic reporting practices. It is particularly important to
      specifically address the important limitations of the methodology, including the
      inability to characterize balanced structural rearrangements and ploidy changes,
      especially if multiplex ligation-dependent probe amplification is to be performed
      alone.

PMID- 21102344
TI  - Assessing remission in major depressive disorder and generalized anxiety disorder
      clinical trials with the discan metric of the Sheehan disability scale.
AB  - Relatively little research has focused on the relationship between functional
      remission and symptomatic remission in mood and anxiety disorders. This study
      investigates the relationship and synchrony between symptomatic and functional
      remission in outpatients with major depressive disorder (MDD) and generalized
      anxiety disorder (GAD). Using data from three MDD (N=1419) and four GAD (N=1847)
      randomized, placebo-controlled duloxetine studies, we calculated the percentages
      of patients meeting symptomatic, functional, and combined functional-symptomatic
      remission criteria for each disorder. We also calculated mean depression [17-item
      Hamilton depression rating scale (HAMD17), Montgomery-Asberg depression rating
      scale] scores and mean anxiety (Hamilton anxiety rating scale) scores for
      patients meeting Sheehan disability scale (SDS) functional remission and the mean
      SDS scores for patients with symptomatic remission. Among the patients with MDD,
      38% achieved symptomatic remission (HAMD17 <= 7), 32% achieved functional
      remission (SDS <= 6), and 23% achieved combined functional-symptomatic remission.
      Mean HAMD17 and Montgomery-Asberg depression rating scale scores for patients
      with functional remission were approximately 6. Mean SDS total scores for
      patients with symptomatic remission were 7.1 (patients with HAMD17 <= 7) and 8.6
      (patients with Montgomery-Asberg depression rating scale <= 10). Among the
      patients with GAD, 30% achieved symptomatic remission (Hamilton anxiety rating
      scale <= 7), 45% achieved functional remission (SDS <= 6), and 25% achieved
      combined symptomatic-functional remission. The mean Hamilton anxiety rating scale
      score in GAD was approximately 8 for patients with functional remission and the
      mean SDS total score was approximately 4 in patients with symptomatic remission.
      The study shows that functional remission does not always move in tandem with
      symptom remission and provides useful anchor points or rules of thumb for
      evaluating symptomatic and functional remission in MDD and GAD.

PMID- 21102345
TI  - Comparison of biexponential and monoexponential model of diffusion weighted
      imaging in evaluation of renal lesions: preliminary experience.
AB  - OBJECTIVES: To obtain intravoxel incoherent motion (IVIM) parameters with
      biexponential analysis of multiple b-value diffusion-weighted imaging (DWI) and
      compare these parameters to apparent diffusion coefficient (ADC) obtained with
      monoexponential modeling in their ability to discriminate enhancing from
      nonenhancing renal lesions. MATERIALS AND METHODS: Twenty-eight patients were
      imaged at 1.5 T utilizing contrast-enhanced (CE) magnetic resonance imaging (MRI)
      and breath-hold DWI using 8 b values (range: 0-800 s/mm(2)). Perfusion fraction
      (f(p)), tissue diffusivity (D(t)), and pseudo-diffusion coefficient (D(p)) were
      calculated using segmented biexponential analysis. ADC(total) and ADC(0-400-800)
      were calculated with monoexponential fitting of the DWI data. f(p), D(t), D(p),
      ADC(total), and ADC(0-400-800) were compared between enhancing and nonenhancing
      renal lesions. Receiver operating characteristic analysis was performed for all
      DWI parameters. f(p) was correlated with percent enhancement. RESULTS: There were
      a total of 31 renal lesions (15 enhancing and 16 nonenhancing) in 28 patients on
      CE-MRI. f(p) of enhancing masses was significantly higher (27.9 vs. 6.1) and D(t)
      was significantly lower (1.47 vs. 2.40 *10(-3) mm(2)/s). IVIM parameters f(p) and
      D(t) demonstrated higher accuracy in differentiating enhancing from nonenhancing
      renal lesions compared with monoexponential parameters ADC(0-400-800) and
      ADC(total), with area under the curve of 0.946, 0.896, 0.854, and 0.675,
      respectively. There was a good correlation between f(p) and percent enhancement
      (r = 0.7; P < 0.001). CONCLUSION: IVIM parameters f(p) and D(t) obtained with
      biexponential fitting of multi-b value DWI have higher accuracy compared with ADC
      (obtained with monoexponential fit) in discriminating enhancing from nonenhancing
      renal lesions. Furthermore, f(p) demonstrates good correlation with percent
      enhancement and can provide information regarding lesion vascularity without the
      use of exogenous contrast agent.

PMID- 21102346
TI  - Solid hypervascular liver lesions: accurate identification of true benign lesions
      on enhanced dynamic and hepatobiliary phase magnetic resonance imaging after
      gadobenate dimeglumine administration.
AB  - PURPOSE: To evaluate hepatobiliary phase magnetic resonance imaging with
      gadobenate dimeglumine for differentiation of benign hypervascular liver lesions
      from malignant or high-risk lesions. METHODS AND MATERIALS: Retrospective
      assessment was performed of 550 patients with 910 hypervascular lesions (302
      focal nodular hyperplasia [FNH], 82 nodular regenerative hyperplasia [NRH], 59
      hepatic adenoma or liver adenomatosis [HA/LA], 329 hepatocellular carcinomas
      [HCC], 12 fibrolamellar-HCC [FL-HCC], 21 peripheral cholangiocarcinomas [PCC],
      105 metastases). Imaging was performed before and during the arterial, portal
      venous, equilibrium, and hepatobiliary phases after gadobenate dimeglumine
      administration (0.05 mmol/kg). Histologic confirmation was available for >=1
      lesion per patient, except for patients with suspected FNH (diagnosis based on
      characteristic enhancement/follow-up). Lesion differentiation (benign/malignant)
      on the basis of contrast washout and lesion enhancement (hypo-/iso
      /hyperintensity) was assessed (sensitivity, specificity, accuracy, PPV, and NPV)
      relative to histology or final diagnosis. RESULTS: On portal-venous or
      equilibrium phase images, washout was not seen for 208 of 526 (39.5%) malignant
      (HCC, FL-HCC, PCC, metastases) and high-risk (HA/LA) lesions. Conversely, only 5
      of 384 (1.3%) true benign lesions (FNH/NRH) showed washout. Taking washout as
      indicating malignancy, the sensitivity, specificity, and accuracy for malignant
      lesion identification during these phases was 61.8%, 98.7%, and 77.4%. On
      hepatobiliary phase images, 289 of 302 FNH, 82 of 82 NRH, 1 of 59 HA or LA, 62 of
      341 HCC or FL-HCC, and 2 of 105 metastases were hyperintense or isointense.
      Taking iso- or hyperintensity as an indication for lesion benignity, the
      sensitivity, specificity, accuracy, PPV, and NPV for benign lesion identification
      was 96.6%, 87.6%, 91.4%, 85.1%, and 97.3%, respectively. CONCLUSIONS:
      Hepatobiliary phase imaging with gadobenate dimeglumine is accurate for
      distinguishing benign lesions from malignant or high-risk lesions. Biopsy should
      be considered for hypointense lesions on hepatobiliary phase images after
      gadobenate dimeglumine.

PMID- 21102347
TI  - Hemodynamic assessment of severe aortic stenosis: MRI evaluation of dynamic
      changes of vena contracta.
AB  - PURPOSE: Direct magnetic resonance imaging (MRI) planimetry of the maximal
      systolic aortic valve area does not consider temporal variations of the opening
      area during the ejection period. We evaluated an MRI-based methodology for the
      assessment of valvular dynamics in patients with severe aortic stenosis by
      measuring the systolic variability of the valvular blood stream, that is, the
      "vena contracta." MATERIALS AND METHODS: With institutional review board
      approval, we examined 22 patients (13 male, 9 female; mean age, 68 +/-10 years)
      with severe aortic stenosis using 1.5 T MRI and a standardized scanning protocol
      consisting of gradient-echo phase-contrast velocity imaging and steady-state free
      precession-cine MRI before and after valve replacement therapy. Temporal changes
      of the aortic valve area, represented by systolic variations of the area of
      poststenotic turbulent flow at its smallest convergence, that is, the proximal
      vena contracta, were determined by MRI and quantified by a calculated parameter
      of temporal valve dynamics (T). T was defined as the period which the aortic
      valve spent over its maximal opening area (>85%) during systole. MRI was also
      used to determine left ventricular hypertrophy before (LVMI) and its regression
      (LVMR) after valve replacement. Findings were compared with transthoracic
      echocardiography and cardiac catheterization. RESULTS: All patients had an
      echocardiographic effective orifice area, EOATTE, of <1.0 cm2. The comparison of
      T to LVMI and LVMR revealed significant correlations (LVMI: r = -0.62; P = 0.002;
      LVMR: r = 0.62; P = 0.002). Further significant correlations with aortic stenosis
      severity were observed in the comparison with manual planimetry, invasive
      measurements, and echocardiographic valve areas, as well as with pressure
      gradients. CONCLUSIONS: MRI can measure systolic variations of the aortic valve
      area. Quantitative parameters of the hemodynamic relevance of valve dynamics
      obtained by this method correlate with established parameters of aortic stenosis
      severity and LVMR.

PMID- 21102348
TI  - Dynamic contrast-enhanced texture analysis of the liver: initial assessment in
      colorectal cancer.
AB  - PURPOSE: To undertake an initial assessment of the potential utility of dynamic
      contrast-enhanced texture analysis (DCE-TA) of the liver in patients with
      colorectal cancer. MATERIALS AND METHODS: TA comprised measurement of mean gray
      level intensity, entropy, and uniformity with and without selective-scale
      filtration using a band-pass filter to highlight different spatial frequencies
      reflecting fine, medium, and coarse textures. An initial phantom study assessed
      the sensitivity of each texture qualifier to computed tomography (CT) acquisition
      parameters. Texture was analyzed in DCE-CT series from 27 colorectal cancer
      patients having apparently normal hepatic morphology (node-negative: n = 8, node
      positive: n = 19). Averaged changes in hepatic texture induced by contrast
      material were assessed qualitatively and quantitatively by using kinetic modeling
      to calculate hepatic perfusion indices following fine, medium, and coarse image
      filtration. RESULTS: All texture qualifiers were less sensitive to changes in CT
      acquisition parameters than measurement of CT attenuation. Temporal changes in
      hepatic texture were qualitatively different from changes in enhancement.
      Statistically significant differences between node-negative and node-positive
      patients were observed for at least 1 time period for measurements of hepatic
      enhancement and for all texture parameters. The differences were most
      statistically significant and occurred over the greatest number of time periods
      for fine texture quantified as mean gray-level intensity (5 time periods, minimum
      P value: 0.006) followed by fine texture quantified as entropy (4 time points,
      minimum P value: 0.006). There was no difference in hepatic perfusion indices for
      the 2 groups. CONCLUSIONS: DCE-TA is a potentially useful adjunct to DCE-CT
      warranting further investigation.

PMID- 21102349
TI  - Magnetic resonance imaging in peripheral arterial disease: reproducibility of the
      assessment of morphological and functional vascular status.
AB  - OBJECTIVES: The aim of the current study was to test the reproducibility of
      different quantitative magnetic resonance imaging (MRI) methods to assess the
      morphologic and functional peripheral vascular status and vascular adaptations
      over time in patients with peripheral arterial disease (PAD). MATERIALS AND
      METHODS: Ten patients with proven PAD (intermittent claudication) and arterial
      collateral formation within the upper leg and 10 healthy volunteers were
      included. All subjects underwent 2 identical MR examinations of the lower
      extremities on a clinical 1.5-T MR system, with a time interval of at least 3
      days. The MR protocol consisted of 3D contrast-enhanced MR angiography to
      quantify the number of arteries and artery diameters of the upper leg, 2D cine MR
      phase contrast angiography flow measurements in the popliteal artery, dynamic
      contrast-enhanced (DCE) perfusion imaging to determine the influx constant and
      area under the curve, and dynamic blood oxygen level-dependent (BOLD) imaging in
      calf muscle to measure maximal relative T2* changes and time-to-peak. Data were
      analyzed by 2 independent MRI readers. Interscan and inter-reader reproducibility
      were determined as outcome measures and expressed as the coefficient of variation
      (CV). RESULTS: Quantification of the number of arteries, artery diameter, and
      blood flow proved highly reproducible in patients (CV = 2.6%, 4.5%, and 15.8% at
      interscan level and 9.0%, 8.2%, and 7.0% at interreader level, respectively).
      Reproducibility of DCE and BOLD MRI was poor in patients with a CV up to 50.9%.
      CONCLUSIONS: Quantification of the morphologic vascular status by contrast
      enhanced MR angiography, as well as phase contrast angiography MRI to assess
      macrovascular blood flow proved highly reproducible in both PAD patients and
      healthy volunteers and might therefore be helpful in studying the development of
      collateral arteries in PAD patients and in unraveling the mechanisms underlying
      this process. Functional assessment of the microvascular status using DCE and
      BOLD, MRI did not prove reproducible at 1.5 T and is therefore currently not
      suitable for (clinical) application in PAD.

PMID- 21102350
TI  - Ovarian choriocarcinoma as the first manifestation of 46,XY pure gonadal
      dysgenesis.
AB  - We report a case of 46,XY pure gonadal dysgenesis (Swyer syndrome) in a
      phenotypically normal 12-year-old girl with a history of vaginal bleeding and
      early breast development, with ovarian choriocarcinoma as the first
      manifestation. The clues leading to the diagnosis included the failure to
      establish any relationship between normal menstrual cycles postoperatively and a
      small remaining contralateral ovary. The correct diagnosis is important for
      cancer prophylaxis and hormonal replacement therapy. Prepubertal and peripubertal
      girls presenting with gonadal germ cell tumors should be carefully evaluated for
      the possibility of underlying gonadal dysgenesis. A history of vaginal bleeding
      or early signs of puberty does not exclude the diagnosis.

PMID- 21102351
TI  - Recurrent alveolar rhabdomyosarcoma with prior surgery and radiotherapy: altered
      lymphatic drainage limits the reliability of sentinel lymph node biopsy.
AB  - A 7-year-old girl was diagnosed with alveolar rhabdomyosarcomas of the right
      crural region. The patient was initially treated with chemotherapy and surgery
      with wide surgical margins, with radiotherapy. The tumors relapsed in the
      popliteal region surrounding the popliteal vessels. The patient received sentinel
      lymph node biopsy for a recurrent tumor using isosulfan blue dye, with the
      "sentinel node" being malignant-negative, and a "nonsentinel node" positive.
      Sentinel lymph node biopsy with conventional blue dye alone might be insufficient
      to assess lymph node status in patients with recurrent rhabdomyosarcoma
      previously treated with surgery and/or radiotherapy.

PMID- 21102352
TI  - Risk factors associated with life-threatening infections in children with febrile
      neutropenia: a data mining approach.
AB  - PURPOSE: To determine risk factors (RFs) and their relationship with life
      threatening infection (LTI) in children with febrile neutropenia (FN). METHOD: In
      this cross-sectional study, from December 2008 to November 2009, all children
      with FN admitted to Dr Sheikh Pediatric Hospital were enrolled. For each patient,
      demographic, clinical, and laboratory data were recorded and they were followed
      up for occurrence of LTI. RESULTS: One hundred and twenty episodes of FN in 68
      patients were analyzed. The most common underlying disease was acute
      lymphoblastic leukemia (53.3%), 9 (7.5%) died from an infection and 35 patients
      (29.1%) had a LTI. Five variables were identified as RFs for LTI, that is, body
      temperature >=39 degrees C (P=0.000), presence of mucositis (P=0.000), abnormal
      chest x-ray (P=0.001), platelet count <20,000/mm (P=0.000), and absolute
      neutrophil count <100/mm (P=0.001). Risk of LTI was increasing according to
      number of RFs presented at the beginning of admission (from 2.8% in patients
      without RF to 100% in patients with 5 RF). Data mining analysis showed
      relationship between RFs with platelet count as the most important variable in
      the high-risk group for LTI. CONCLUSIONS: Evaluation of important RFs and judging
      the severity of patients' condition by studying the importance and relationship
      between RF at the time of admission can be a useful method for screening LTI in
      children with FN.

PMID- 21102353
TI  - Development of T-cell acute lymphoblastic leukemia in a patient in very long
      lasting complete remission of juvenile myelomonocytic leukemia.
AB  - Juvenile myelomonocytic leukemia (JMML) occurs with an incidence of 1.2 per
      million children a year, and represents 18% to 30% of all myelodysplastic (MDS)
      and myeloproliferative (MPS) disorders in the age group below 15, being by far
      the most common MDS/MPS in children younger than 4 years. The only therapeutic
      approach which results in a definitive cure of patients with JMML is
      myeloablative chemo-therapy/radio-therapy, followed by allogeneic hematopoietic
      cell transplantation. Few cases of transformation of JMML in acute lymphoblastic
      leukemia have been reported. We describe a child with JMML diagnosed at the age
      of 4 months in whom complete remission was achieved with 13-cis retinoic acid and
      cytosine-arabinoside and was sustained for 7 years with no maintenance therapy.
      Ninety-eight months after the diagnosis of JMML was established, overt T-cell
      leukemia developed. Treatment with acute lymphoblastic leukemia (ALL)-directed
      chemotherapy induced complete restoration of normal hemopoiesis, but testicular
      involvement persisted. The patient died after transplantation with unrelated cord
      blood. This case suggests that JMML is a true stem cell disorder and that stem
      cell transplantation should be considered, even in patients with a very favorable
      clinical course.

PMID- 21102354
TI  - Twice weekly Pneumocystis jiroveci pneumonia prophylaxis with trimethoprim
      sulfamethoxazole in pediatric patients with acute lymphoblastic leukemia.
AB  - BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) prophylaxis has become the
      standard of care for immunocompromised patients secondary to human
      immunodeficiency virus, chemotherapy, or prolonged steroid usage. The current
      recommendations for PCP prophylaxis are for trimethoprim-sulfamethoxazole
      (TMP/SMX) therapy on 3 consecutive days per week. Our hospital has been using
      twice weekly TMP/SMX for our pediatric patients with acute lymphoblastic leukemia
      (ALL) for a number of years. METHODS: We performed a retrospective review of all
      our pediatric ALL patients from November 1998 to November 2003. We looked
      specifically for chest radiograph findings, pathologic reports, bronchoalveolar
      lavages, or discharge diagnoses by the International Classification of Diseases,
      9th revision code consistent with PCP. Those cases suspicious for PCP infection
      had their medical records reviewed in detail. RESULTS: Eighty-seven patients were
      treated with TMP/SMX prophylaxis during the study period for a total of 56,483
      patient days with no proven cases of PCP. These results are similar to studies of
      either daily or thrice weekly TMP/SMX prophylaxis for pediatric ALL patients, and
      more recent studies also using twice weekly TMP/SMX prophylaxis. CONCLUSIONS:
      Twice weekly TMP/SMX seems to be a reasonable alternative for PCP prophylaxis for
      pediatric ALL patients. In review of other recent publications on pediatric
      patients, this recommendation can likely be extended to other pediatric
      malignancies as well. Further study is required to determine the appropriate
      length of prophylaxis and whether once weekly TMP/SMX prophylaxis or SMX alone at
      current or smaller doses could provide effective prophylaxis.

PMID- 21102355
TI  - Double-chambered left ventricle due to fibroelastotic membrane: an unusual case.
AB  - We describe a rare case of a double-chambered left ventricle caused by a
      fibroelastotic membrane that was clearly delineated using echocardiography and
      magnetic resonance imaging, which resulted in successful surgical correction.

PMID- 21102356
TI  - 64-slice multidetector-row computed tomography in the diagnosis of coronary
      artery disease: interobserver agreement among radiologists with varied levels of
      experience on a per-patient and per-segment basis.
AB  - PURPOSE: To assess the interobserver variability of 4 radiologists with different
      levels of experience in the evaluation of 64-slice coronary computed tomographic
      angiography (cCTA). MATERIALS AND METHODS: Two board-certified radiologists with
      10 and 8 years of experience in reading cCTA and 2 radiology residents, 1 with 3
      years of experience in reading cCTA and 1 with experience in reading general
      computed tomographic scans but without dedicated cCTA training, participated in
      the study. All the observers independently analyzed 50 cCTA studies for signs of
      coronary artery disease (stenosis of 0%, <=49%, 50% to 74%, 75% to 99%, or 100%).
      Diagnostic accuracy of the 4 readers for stenosis detection on cCTA was compared
      with that of conventional angiography on a per-segment and per-patient basis. No
      patients, vessels, or segments were excluded from analysis. RESULTS: On a per
      segment basis, correlation between cCTA and invasive coronary angiography was
      good for readers with more than 10 (r=0.75), more than 8 (r=0.75), and more than
      3 (r=0.73) years of cCTA experience. The correlation coefficient was poor
      (r=0.39) for the untrained reader. Sensitivity was not significantly (P=0.56)
      different between observers with more than 8 and more than 10 years of experience
      but was significantly (P>0.05) lower for the reader with less than 3 years
      experience and for the untrained reader. However, we found no significant
      difference in overall diagnostic accuracy on a per-patient (P=0.86) and on a per
      segment level (P=0.72) among the 4 readers. CONCLUSION: The level of experience
      significantly influences the sensitivity of coronary artery stenosis detection at
      cCTA, and thus highlights the need for dedicated training in cCTA interpretation.

PMID- 21102357
TI  - Family and friend participation in primary care visits of patients with diabetes
      or heart failure: patient and physician determinants and experiences.
AB  - BACKGROUND: Professional and patient groups have called for increased
      participation of patients' informal support networks in chronic disease care, as
      a means to improve clinical care and self-management. Little is known about the
      current level of participation of family and friends in the physician visits of
      adults with chronic illnesses or how that participation affects the experience of
      patients and physicians. METHODS: Written survey of 439 functionally independent
      adults with diabetes or heart failure and 88 of their primary care physicians
      (PCPs). Patients were ineligible if they had a memory disorder, needed help with
      activities of daily living, or were undergoing cancer treatment. RESULTS:
      Nonprofessional friends or family ("companions") regularly participated in PCP
      visits for nearly half (48%) of patients. In multivariable models, patients with
      low health literacy (adjusted odds ratio [AOR]: 2.9, confidence interval [CI]:
      1.4-5.7), more depressive symptoms (AOR: 1.3, CI: 1.1-1.6), and 4 or more
      comorbid illnesses (AOR: 3.7, CI: 1.3-10.5) were more likely to report companion
      participation. Patients reported that they were more likely to understand PCP
      advice (77%) and discuss difficult topics with the physician (44%) when
      companions participated in clinic visits. In multivariable models, companion
      participation was associated with greater patient satisfaction with their PCP
      (AOR: 1.7, CI: 1.1-2.7). Most PCPs perceived visit companions positively, however
      66% perceived 1 or more barriers to increasing companion participation, including
      increased physician burden (39%), inadequate physician training (27%), and
      patient privacy concerns (24%). CONCLUSION: Patients' companions represent an
      important source of potential support for the clinical care of functionally
      independent patients with diabetes or heart failure, particularly for patients
      vulnerable to worse outcomes. Companion participation in care was associated with
      positive patient and physician experiences. Physician concerns about companion
      participation are potentially addressable through existing training resources.

PMID- 21102358
TI  - Variation in the quality of surgical care for uterovaginal prolapse.
AB  - BACKGROUND: Pelvic organ prolapse is a common disorder, affecting an estimated
      24% of women in the United States, with more than 200,000 surgical procedures
      performed annually. Current treatment recommendations from the American College
      of Obstetricians and Gynecologists include pelvic floor reconstruction (or pexy)
      procedures to correct prolapse, with or without hysterectomy; however, many women
      are treated by hysterectomy alone. OBJECTIVE: To determine whether hospital
      characteristics predict compliance with recommended surgical care for
      uterovaginal prolapse. METHODS: Retrospective analysis of linked California
      hospital discharge and financial data. International Classification of Diseases,
      ninth Edition Clinical Modification codes identified records with a primary
      diagnosis of prolapse and concomitant coding for surgical procedures. chi2
      analysis and multivariable models were used to characterize the associations
      between hospital characteristics and compliance. Compliant care was defined as
      prolapse treatment by pelvic floor reconstruction (pexy) procedure with or
      without hysterectomy. Failed compliance was defined as hysterectomy alone.
      RESULTS: A total of 28,539 cases in 343 hospitals were analyzed. Low compliance
      rates were detected in all hospital types, though some were better than others.
      High-volume (odds ratios [OR] = 1.75; 95% CI: [1.62, 1.89]), teaching (OR = 2.03;
      95% CI: [1.84, 2.25]), and private (OR = 1.28; 95% CI: [1.14, 1.46]) hospitals
      were more likely, while disproportionate share hospitals were less likely (OR =
      0.58; 95% CI: [0.54, 0.63]) to comply with evidence-based recommendation.
      CONCLUSION: Although we did find significant variation in compliance by hospital
      characteristics, compliance rates were low in all settings. Quality improvement
      efforts in the surgical treatment of uterovaginal prolapse should focus on
      increasing adherence to evidence-based practice.

PMID- 21102359
TI  - Cytoplasmic Ca2+ concentration changes evoked by muscarinic cholinergic
      stimulation in primary and metastatic melanoma cell lines.
AB  - Experiments were performed to explore differences between cultured primary and
      metastatic melanoma cell lines in their muscarinic acetylcholine receptor
      mediated intracellular Ca signalization. The expression of type 1 and type 3
      muscarinic receptors was detected and compared at the protein level using both
      immunocytochemistry and semiquantitative western blotting. The functionality of
      muscarinic receptors was tested by applying carbamylcholine (CCh; 1 mmol/l) and
      by recording the associated increases in cytoplasmic Ca using Ca imaging with the
      application of the Ca indicator dye, fluo-4. These data indicate that the
      expression levels of the receptor proteins were not significantly different in
      the metastatic (HT199, HT168-M1) and the primary (WM35) cell lines. Although Ca
      transients were evoked in all the three cell lines by CCh, the proportion of the
      CCh-positive cells was smaller amongst the WM35 cells. The Ca transients could be
      effectively blocked by atropine (0.1 mmol/l). The time courses of the Ca
      transients were highly variable, and in some instances they showed a late
      (plateau-like) component whose presence crucially depended on the influx of
      extracellular Ca. When the extracellular Ca concentration was reduced, the
      duration of the CCh-evoked transients was considerably decreased; a phenomenon
      that was more pronounced in the metastatic cell lines. Although there are no
      fundamental differences in the muscarinic receptor-mediated Ca signalization of
      the primary and metastatic cell lines, the quantitative differences showed in
      this study may partially explain the increased malignancy and migratory potential
      of the metastatic cells. 

PMID- 21102360
TI  - Does complete response to systemic therapy in patients with stage IV melanoma
      translate into long-term survival?
AB  - The aim of this study was to determine the impact of complete response (CR) to
      systemic therapy on survival. We reviewed the cases of 647 chemo-naive patients
      with metastatic melanoma who were treated with cisplatin-vinblastine-dacarbazine
      or cisplatin-taxol-dacarbazine alone, or cisplatin-vinblastine-dacarbazine
      together with interferon alpha or interleukin-2 plus interferon alpha. After
      excluding patients with uveal melanoma and patients who had resection of
      metastases, 567 patients were eligible to participate in this analysis. An event
      chart is presented for the 51 patients with CR and for three random samples of
      patients without CR. We compared overall survival of responders versus
      nonresponders using response as a time-dependent covariate in a Cox proportional
      hazards model. In addition, we used the landmark method, choosing 6 months as the
      landmark. Logistic regression techniques were used to determine factors
      associated with CR to therapy. All P values were 2-tailed and considered
      significant at alpha less than 0.05. Analyses were conducted using SAS for
      Windows. In this analysis, CR was associated with patients who were younger,
      male, and who had better performance status, lower M-stage, no liver metastases,
      and no visceral sites involved, normal LDH and had received biochemotherapy.
      While accounting for these factors, the relationship between CR and survival
      remained statistically significant, suggesting a causal relationship between
      response and survival. Using 6-month landmark analysis method, we still find a
      significant difference in overall survival between response groups, favoring
      patients who achieved CR with systemic therapy. In conclusion, CR to systemic
      therapy is associated with long-term survival in patients with stage IV melanoma.

PMID- 21102361
TI  - Circle back before moving forward.

PMID- 21102362
TI  - Comparison of pandemic and seasonal influenza reveals higher mortality and
      increased prevalence of shock in children with severe h1n1/09 infection.
AB  - Comparison of the clinical features of H1N1/09 and previous years' influenza A
      cases reveals that, in children presenting with severe disease, H1N1/09 influenza
      is associated with an increased prevalence of shock, duration of admission, and
      mortality. This was not attributable to demographic differences or underlying
      disease. H1N1/09 influenza is associated with more severe diseases than those
      with previous years' influenza A strains.

PMID- 21102363
TI  - Anthroposophy: a risk factor for noncompliance with measles immunization.

PMID- 21102364
TI  - T-shaped scleral buckle for macular detachments in high myopes.

PMID- 21102365
TI  - Diagnostic and therapeutic challenges.

PMID- 21102366
TI  - Early change of central macular thickness after intravitreous triamcinolone or
      bevacizumab in diabetic macular edema or retinal vein occlusion.
AB  - PURPOSE: To evaluate the immediate changes after intravitreous triamcinolone
      acetonide or intravitreous bevacizumab in diabetic macular edema (DME). METHODS:
      A nonrandomized interventional study. Type 2 diabetic patients were included.
      Intravitreous triamcinolone acetonide (4 mg) was injected for 22 eyes with DME
      and IVB (1.25 mg) for 18 eyes with DME. The early time-dependent changes of
      central macular thickness were evaluated by optical coherence tomography before
      and from 1 hour to 1 month after intervention. Intravitreous bevacizumab was also
      tested in patients with retinal vein occlusion as a control of non-DME. Visual
      acuity was also examined. RESULTS: Compared with the baseline, central macular
      thickness of eyes with DME decreased significantly 1 hour after intravitreous
      triamcinolone acetonide (P < 0.05, Wilcoxon signed rank test), while it did not
      significantly until 24 hours after IVB. The decrease in central macular thickness
      was observed significantly from 3 hours after IVB in retinal vein occlusion (P <
      0.05, Wilcoxon signed rank test), and it was more evident in retinal vein
      occlusion than DME after IVB. Visual acuity improved significantly in DME with
      intravitreous triamcinolone acetonide or IVB at 1 month (P < 0.01 and P < 0.05,
      respectively, Wilcoxon signed rank test). CONCLUSION: Factors responsive to
      triamcinolone acetonide, other than vascular endothelial growth factor, might
      play an important role in pathogenesis of DME compared with retinal vein
      occlusion. Although no conclusion can be drawn, immediate decrease in central
      macular thickness after intravitreous triamcinolone acetonide might indicate the
      possible involvement of a nongenomic pathway of triamcinolone acetonide action.

PMID- 21102368
TI  - Improved visualization of Henle fiber layer by changing the measurement beam
      angle on optical coherence tomography.
AB  - PURPOSE: The outer plexiform layer (OPL) includes the photoreceptor synapse layer
      and Henle fiber layer (HFL) in the macular area. We attempted to improve optical
      coherence tomography imaging of the HFL by changing the angle of the measurement
      beam. METHODS: Thirteen normal eyes underwent spectral domain optical coherence
      tomography. To focus the angle of the measurement beam perpendicular to the
      obliquely oriented HFL, the beam in the optical coherence tomography system was
      aimed at the periphery of the pupil. RESULTS: The cross-sectional image of the
      macular area was inclined right or left if the beam entered from the periphery of
      the pupil. The reflectivity of the OPL increased because of strong backscattering
      of light in the half of the macula that was tilted down in cross-sectional
      images. On the opposite side, the reflectivity of HFL (the outer two-thirds of
      the OPL) decreased compared with that of the outer nuclear layer, but the
      photoreceptor synapse layer (the inner one-third of the OPL) remained highly
      reflective. The mean thicknesses of the OPL that could be visualized 1.0 mm and
      1.5 mm from the central fovea were 73.7 +/- 7.0 MUm and 64.1 +/- 8.2 MUm,
      respectively. CONCLUSION: Positioning the measurement beam perpendicular to HFL
      enhanced visualization performance.

PMID- 21102367
TI  - Posterior lattice degeneration characterized by spectral domain optical coherence
      tomography.
AB  - PURPOSE: The purpose of this study was to use high-resolution spectral domain
      optical coherence tomography in the characterization of retinal and vitreal
      morphological changes overlying posterior lattice degeneration. METHODS: A cross
      sectional retrospective analysis was performed on 13 eyes of 13 nonconsecutive
      subjects with posterior lattice degeneration seen at the New England Eye Center,
      Tufts Medical Center between October 2009 and January 2010. Spectral domain
      optical coherence tomography images taken through the region of lattice
      degeneration were qualitatively analyzed. RESULTS: Four characteristic changes of
      the retina and vitreous were seen in the 13 eyes with lattice degeneration: 1)
      anterior/posterior U-shaped vitreous traction; 2) retinal breaks; 3) focal
      retinal thinning; and 4) vitreous membrane formation. The morphologic appearance
      of vitreous traction and retinal breaks were found to be consistent with previous
      histologic reports. CONCLUSION: It is possible to image posterior lattice
      degeneration in many eyes using spectral domain optical coherence tomography and
      to visualize the spectrum of retinal and vitreous changes throughout the area of
      lattice degeneration.

PMID- 21102369
TI  - Randomized trial of anesthetic methods for intravitreal injections.
AB  - PURPOSE: To compare the effectiveness of four different anesthetic methods for
      intravitreal injection. METHODS: Twenty-four patients each received four
      intravitreal injections using each of four types of anesthesia (proparacaine,
      tetracaine, lidocaine pledget, and subconjunctival injection of lidocaine) in a
      prospective, masked, randomized block design. Pain was graded by the patient on a
      0 to 10 scale for both the anesthesia and the injection. RESULTS: The average
      combined pain scores for both the anesthesia and the intravitreal injection were
      4.4 for the lidocaine pledget, 3.5 for topical proparacaine, 3.8 for the
      subconjunctival lidocaine injection, and 4.1 for topical tetracaine. The
      differences were not significant (P = 0.65). There were also no statistical
      differences in the individual anesthesia or injection pain scores.
      Subconjunctival lidocaine injection had the most side effects. CONCLUSION:
      Topical anesthesia is an effective method for limiting pain associated with
      intravitreal injections.

PMID- 21102371
TI  - Acquired Vitelliform Lesions: correlation of clinical findings and multiple
      imaging analyses.
AB  - PURPOSE: To correlate clinical observations with multimodal imaging analysis in
      acquired vitelliform lesions (AVLs) and to elucidate their nature, pathogenesis,
      and natural course. METHODS: Clinical examination, color fundus photography,
      fluorescein angiography, near-infrared reflectance, fundus autofluorescence, and
      spectral-domain optical coherence tomography (SD-OCT) data were retrospectively
      reviewed for a consecutive series of 90 eyes of 67 patients with an AVL secondary
      to a variety of diagnoses. RESULTS: In all 90 eyes with AVLs, SD-OCT helped
      localize the clinically apparent yellowish material to the subretinal space above
      the retinal pigment epithelial (RPE) band. Only 19 eyes (21.1%) had SD-OCT
      evidence of subretinal fluid. All eyes exhibited abnormal hyperautofluorescence
      corresponding to the material seen clinically. In 18 of 72 eyes (25.0%) imaged
      simultaneously with SD-OCT and near-infrared reflectance imaging, near-infrared
      hyperreflectivity corresponding to presumed collections of pigment-laden
      macrophages and RPE cells was observed. Resolution of some AVLs appeared to
      coincide with progressive thinning of the outer nuclear layer, indicating a
      gradual loss of photoreceptors. Visual acuity at baseline was best predicted by
      the subfoveal integrity of the external limiting membrane (P = 0.001) and the
      inner segment/outer segment junction (P = 0.0002) on SD-OCT. Fluorescein
      angiography revealed a pattern often mimicking poorly defined (Type 1) choroidal
      neovascularization. CONCLUSION: Acquired vitelliform lesions occur in a variety
      of different clinical entities that share common features with multimodal imaging
      analyses. We propose that both dysfunctional RPE and loss of apposition between
      the photoreceptor tips and the RPE can interfere with the phagocytosis of shed
      outer segments. Both this material and pigment-laden macrophages and RPE cells
      appear to contribute to the yellowish appearance of AVLs. Ongoing photoreceptor
      loss may in some cases be associated with the spontaneous resolution of an AVL.

PMID- 21102372
TI  - Cilioretinal arteries in diabetic eyes are associated with increased retinal
      blood flow velocity and occurrence of diabetic macular edema.
AB  - PURPOSE: The main purpose was to investigate the relationship between occurrence
      of cilioretinal arteries and macular edema in diabetic eyes in terms of retinal
      blood flow characteristics revealed by the Retinal Function Imager (RFI). Other
      standard imaging techniques such as fundus photography, fluorescein angiography,
      and spectral-domain optical coherence tomography/scanning laser ophthalmoscopy
      were also used along with the RFI. The additional purpose was to look for the
      evidence of cilioretinal-retinal collaterals using the RFI. METHODS: Patients
      with a diagnosis of diabetic retinopathy were included. All patients underwent
      fundus photography, fluorescein angiography, spectral-domain optical coherence
      tomography, and imaging using RFI. The presence of cilioretinal artery (CilRA)
      was recognized using color/red-free fundus photographs, fluorescein angiography,
      and RFI. There were two groups according to the presence (CilRA group) or absence
      (NoCilRA group) of cilioretinal artery or arteries in the study eye. RESULTS:
      Thirty-nine eyes with diabetic retinopathy were included. Cilioretinal artery was
      identified in 15 eyes (38%). In the CilRA group, spectral-domain optical
      coherence tomography evidence of macular edema was observed in 13 of 15 eyes
      (87%), whereas in the NoCilRA group, macular edema was observed on spectral
      domain optical coherence tomography in 7 of 24 eyes (29%). Mean blood flow
      velocities in retinal arteries and veins were significantly higher in diabetic
      eyes with cilioretinal artery (P = 0.04 and P = 0.005, respectively). Mean blood
      velocity in cilioretinal arteries was significantly higher in comparison with the
      mean arterial blood velocity (P = 0.03). In the CilRA group, cilioretinal-retinal
      collaterals, assessed by RFI, were detected in 4 of 15 eyes (27%) with
      cilioretinal arteries. In the NoCilRA group, mean blood velocity in retinal veins
      was significantly higher in eyes with macular edema in comparison with those
      without macular edema (P = 0.03). CONCLUSION: Using the RFI in conjunction with
      standard fundus imaging techniques, the presence of cilioretinal artery in
      diabetic eyes was found to be associated with increased retinal blood flow
      velocity and increased occurrence of diabetic macular edema. The occurrence of
      cilioretinal-retinal collaterals was also noted; however, the pathophysiologic
      significance of this finding requires further investigation.

PMID- 21102370
TI  - Long-term results of combined endoscope-assisted pars plana vitrectomy and
      glaucoma tube shunt surgery.
AB  - PURPOSE: To assess outcomes after endoscope-assisted pars plana vitrectomy with
      concurrent pars plana tube shunt placement. METHODS: Records of 18 adult patients
      (19 eyes) with uncontrolled chronic angle-closure glaucoma associated with
      corneal opacification or fibrosed pupils were retrospectively reviewed. All eyes
      underwent endoscope-assisted pars plana vitrectomy with Baerveldt tube shunt
      placement into the vitreous cavity between 1997 and 2005. Intraocular pressure
      reduction, glaucoma medication reduction, complications, and visual acuity were
      analyzed. RESULTS: Mean follow-up duration was 62 months (range, 10-106 months).
      Mean preoperative intraocular pressure was 31.3 +/- 10.5 mmHg on 3.4 +/- 1.0
      glaucoma medications. Intraocular pressure was significantly reduced at each
      postoperative time point examined. In the 17 eyes without phthisis, intraocular
      pressure was significantly reduced at the final follow-up examination to a mean
      of 11.4 +/- 2.9 mmHg (P < 0.0001) on 1.3 +/- 1.2 medications (P < 0.0001). No
      complications occurred in 14 of 19 eyes. Postoperatively, best-attained visual
      acuity improved in 14 of 19 eyes, remained unchanged in 4 of 19 eyes, and was
      reduced in 1 of 19 eyes. CONCLUSION: Combined endoscope-assisted pars plana
      vitrectomy with placement of a Baerveldt tube shunt into the vitreous cavity is a
      useful intervention in patients with uncontrolled chronic angle-closure glaucoma,
      media opacities, and limited surgical options.

PMID- 21102373
TI  - Optical coherence tomography for evaluation of photodynamic therapy in
      symptomatic circumscribed choroidal hemangioma.
AB  - PURPOSE: To evaluate the results of photodynamic therapy for circumscribed
      choroidal hemangioma by optical coherence tomography. METHODS: A retrospective
      review of 14 eyes with systematic circumscribed choroidal hemangioma receiving
      photodynamic therapy was evaluated by time-domain optical coherence tomography.
      Central retinal thickness and foveal photoreceptor layer thickness were assessed,
      including the status of the junction between the inner and the outer segments of
      the photoreceptors (IS/OS) in the fovea at the final examination. RESULTS: The
      optical coherence tomography findings included 9 eyes (64.3%) with foveal cystoid
      edema, 9 eyes (64.3%) with subretinal fluid, and 1 eye (7.1%) with foveal
      thinning. After photodynamic therapy, optical coherence tomography showed
      absorbed subretinal fluid in 9 eyes and resolved edema in 7 of 9 eyes, with
      significantly decreased central retinal thickness (440 +/- 214 vs. 175 +/- 66
      MUm, P = 0.003). IS/OS lines were observed in 4 eyes, which had a better final
      visual acuity (VA) (20/40-20/17) and a mean foveal photoreceptor layer thickness
      of 127.3 +/- 5.6 MUm. The remaining 10 eyes with an invisible IS/OS line had a
      poorer final VA and an attenuated foveal photoreceptor layer. The final VA was
      significantly correlated with initial VA (r = 0.796, P = 0.001) and foveal
      photoreceptor layer thickness at the final examination (r = -0.832, P = 0.001).
      CONCLUSION: Optical coherence tomography was useful for evaluating VA loss and
      prognosis in circumscribed choroidal hemangioma. Resolved foveal edema, absorbed
      subretinal fluid, and preserved photoreceptors contributed to the prognosis of
      photodynamic therapy for circumscribed choroidal hemangioma.

PMID- 21102374
TI  - Kinetics of adipose tissue microdialysis-derived metabolites in critically ill
      septic patients: associations with sepsis severity and clinical outcome.
AB  - Microdialysis (MD) provides the opportunity to monitor tissue metabolic changes.
      This study aimed to describe the kinetics of MD-derived metabolites during the
      course of critical sepsis, to assess whether these metabolites are useful in
      grading sepsis severity, and to investigate their prognostic use. To this end, 54
      mechanically ventilated septic patients were prospectively studied, out of which
      39 had shock. Upon sepsis onset, an MD catheter was inserted into the
      subcutaneous adipose tissue of the upper thigh. Dialysate samples were analyzed
      for glucose, pyruvate, lactate, and glycerol. Sampling was performed six times
      per day for a maximum of 6 days. The daily mean values of MD measurements were
      calculated for each patient. Arterial blood was analyzed for glucose, lactate,
      and glycerol concomitantly with dialysate sampling. Blood glucose and tissue
      glucose levels along with lactate levels were high during the entire study
      period. Tissue pyruvate and glycerol were also raised, whereas the lactate
      pyruvate ratio was preserved. At study entry, patients with septic shock had
      higher tissue lactate (3.3 vs. 1.9 mmol/L, P = 0.01) and glycerol (340 vs. 169
      MUmol/L, P = 0.04) levels compared with those without shock. Nonsurvivors had
      higher tissue lactate (P = 0.008), glycerol (P = 0.004), and pyruvate (P = 0.002)
      levels than survivors during the whole observation period. Logistic regression
      analysis showed that age (odds ratio [OR], 1.075; 95% confidence interval [CI],
      1.004-1.150; P = 0.03), Sequential Organ Failure Assessment score on day 1 (OR,
      1.550; 95% CI, 1.043-2.312; P = 0.03), and tissue glycerol on day 1 (OR, 1.007;
      95% CI, 1.001-1.012; P = 0.01) predicted mortality independently. In conclusion,
      critical sepsis is characterized by high tissue lactate and pyruvate levels and a
      preserved lactate-pyruvate ratio, suggesting a nonischemic mechanism for raised
      blood lactate levels. Septic shock is associated with higher tissue lactate and
      glycerol levels compared with sepsis without shock. Elevated tissue lactate,
      pyruvate, and glycerol levels are related to poor clinical outcome, with the
      latter constituting an independent predictor.

PMID- 21102375
TI  - Selective inhibitory effect of epigallocatechin-3-gallate on migration of
      vascular smooth muscle cells.
AB  - In order to prevent restenosis after angioplasty or stenting, one of the most
      popular targets is suppression of the abnormal growth and excess migration of
      vascular smooth muscle cells (VSMCs) with drugs. However, the drugs also
      adversely affect vascular endothelial cells (VECs), leading to the induction of
      late thrombosis. We have investigated the effect of epigallocatechin-3-gallate
      (EGCG) on the proliferation and migration of VECs and VSMCs. Both cells showed
      dose-dependent decrease of viability in response to EGCG while they have
      different IC(50) values of EGCG (VECs, 150 mM and VSMCs, 1050 mM). Incubating
      both cells with EGCG resulted in significant reduction in cell proliferation
      irrespective of cell type. The proliferation of VECs were greater affected than
      that of VSMCs at the same concentrations of EGCG. EGCG exerted differential
      migration-inhibitory activity in VECs vs. VSMCs. The migration of VECs was not
      attenuated by 200 mM EGCG, but that of VSMCs was significantly inhibited at the
      same concentration of EGCG. It is suggested that that EGCG can be effectively
      used as an efficient drug for vascular diseases or stents due to its selective
      activity, completely suppressing the proliferation and migration of VSMCs, but
      not adversely affecting VECs migration in blood vessels.

PMID- 21102376
TI  - Synthesis of seco-chlorinated derivatives of phenanthroindolizidine precursors
      via Friedel-Crafts reaction.
AB  - In the course of synthesizing 3-demethyltylophorine (1) by Lewis acid catalyzed
      intramolecular Friedel-Crafts reaction starting from N-(3-hydroxy-2,6,7
      trimethoxy-phenanthr-9-ylmethyl)-2-chloromethylpyrrolidine, two chlorinated
      phenanthrene derivatives N-(4,10-dichloro-3-hydroxy-2,6,7-trimethoxyphenanthr-9
      ylmethyl)-2-chloromethylpyrrolidine (4) and N-(4-chloro-3-hydroxy-2,6,7
      trimethoxyphenanthr-9-ylmethyl)-2-chloromethylpyrrolidine (5) were obtained. The
      structures of these compounds were determined by spectroscopic analysis.

PMID- 21102377
TI  - Antioxidant, anti-inflammatory and anti-influenza properties of components from
      Chaenomeles speciosa.
AB  - The fruit of Chaenomeles speciosa is a traditional Chinese medicine used for the
      treatment of dyspepsia and various inflammatory diseases. In the present study,
      we evaluated the potential radical scavenging capacity, and activity against
      nitrous oxide, inflammatory cytokines production and neuramindase (NA) of its
      isolates. The results showed that 3,4-dihydroxybenzoic acid (1) displayed higher
      inhibitory activities on DPPH and NA with IC(50) values of 1.02 mg/mL and 1.27
      mg/mL respectively, and quercetin (2) also showed significant inhibitory action
      on DPPH and NA, with IC(50 )values of 3.82 mg/mL and 1.90 mg/mL. Compounds 1, 2
      and methyl 3-hydroxybutanedioic ester (3) could inhibit the production of TNF-a
      by 22.73%, 33.14% and 37.19% at 5 mg/mL (P < 0.05) compared with the control. In
      addition, compound 2 was found to be active on the release of IL-6 in RAW264.7
      macrophage cells, with an inhibitory rate of 39.79% (P < 0.05). The anti
      inflammatory effect of compound 3 is disclosed for the first time in this study.
      Avian influenza is usually accompanied by virus invasion followed by the
      occurrence of oxidative stress and serious inflammation, so the multiple effects
      of the isolates may play a cocktail-like role in the treatment of avian
      influenza, and C. speciosa components, especially quercetin, might be a potent
      source for anti-viral and anti-inflammatory agents.

PMID- 21102379
TI  - Urinary hepatocyte growth factor indicates ischemia/reperfusion injury after
      kidney transplantation.
AB  - INTRODUCTION: Despite the development of immunosuppressive regimens in kidney
      transplantation, long-term graft survival rates have not increased significantly.
      One of the causes of long-term graft loss is ischemia-reperfusion insult.
      Hepatocyte growth factor (HGF) is a regenerative factor produced in response to
      injury. OBJECTIVES: Our aim was to assess the effect of HGF and xanthine oxidase
      (indicators of ischemia/reperfusion insult) on early and late kidney function.
      PATIENTS AND METHODS: In 17 patients, HGF levels in urine and xanthine oxidase
      activity in blood were examined 1, 7, 14, 30 days, 3 and 6 months after kidney
      transplantation. We also measured 24-hour diuresis and serum creatinine levels
      after transplantation. RESULTS: Urinary HGF levels were highest 1 day after
      transplantation. During the following week, it rapidly decreased and was
      maintained at similar levels in the later period. Creatinine at 1 day showed a
      positive correlation with urinary HGF levels at 1 day and at 3 months (R = 0.54,
      P <0.05 and R = 0.82, P <0.01, respectively). Creatinine at 7 days positively
      correlated with HGF levels at 6 months (R = 0.82, P <0.05). HGF levels at 1 day
      and at 6 months positively correlated with xanthine oxidase activity at 1 day (R
      = 0.73, P <0.001 and R = 0.77, P <0.02, respectively). A negative correlation was
      observed between HGF levels at 6 months and diuresis 1 and 7 days after
      transplantation (R = -0.99, P <0.00 001 and R = -0.77, P <0.05, respectively).
      CONCLUSIONS: Urinary HGF is a good marker of perioperative kidney damage and may
      affect long-term graft function.

PMID- 21102378
TI  - Characterization of phosphate solubilizing bacteria in sediments from a shallow
      eutrophic lake and a wetland: isolation, molecular identification and phosphorus
      release ability determination.
AB  - The transformation of phosphorus (P) is a major factor of lake eutrophication,
      and phosphate releasing bacteria play an important role in the release process.
      Experiments were conducted to investigate P content and characterize phosphate
      solubilizing bacterial composition at the molecular level in a shallow eutrophic
      lake and a wetland. Results showed that P concentrations were relatively high and
      derived from agricultural runoff and domestic or industrial pollution.
      Enumeration and molecular identification of these strains indicated that these
      bacterial groups were abundant in the ecosystem and various kinds of bacteria
      participated in the phosphorus release process. Twelve phosphate solubilizing
      bacteria, including eight organic P-solubilizing bacteria (OPBs) and four
      inorganic P-solubilizing bacteria (IPBs), which belonged to three different
      families, were isolated and identified. Cupriavidus basilensis was found for the
      first time to have the ability to mineralize organic P (OP). Laboratory tests on
      P release ability revealed that IPBs were more effective at releasing P than
      OPBs. The most efficient IPB strain could accumulate over 170 mg.L-1
      orthophosphate, while the equivalent OPB strain only liberated less than 4 mg.L-1
      orthophosphate in liquid culture. The results obtained from this investigation
      should help clarify the roles of microorganisms in aquatic systems and the
      mechanisms of eutrophication.

PMID- 21102380
TI  - Multicenter, open-label, nonrandomized, observational safety study in subjects
      using insulin aspart in basal-bolus regimen for the treatment of diabetes.
AB  - INTRODUCTION: Basal-bolus insulin therapy is a standard method of intensifying
      diabetes treatment. A common adverse effect of such treatment is hypoglycemia.
      Data on frequency of hypoglycemia when fast-acting insulin analogue is used in
      everyday clinical practice is scarce. OBJECTIVES: The aim of the study was to
      investigate the risk of hypoglycemia after the use of insulin aspart in basal
      bolus therapy in patients with type 1 and 2 diabetes. PATIENTS AND METHODS: It
      was a multicenter, open-label, noninterventional study. It involved 950 patients
      with type 1 and 1332 patients with type 2 diabetes who started preprandial
      insulin aspart in basal-bolus regimen. Patients were followed for 13 weeks. The
      primary endpoint was the incidence of major daytime and nocturnal hypoglycemic
      events assessed on the basis of patients' self-reports during follow-up compared
      with a 4-week period before the baseline visit. Secondary endpoints were:
      incidence of minor daytime and nocturnal hypoglycemia, hemoglobin A1c (HbA1c),
      fasting and postprandial glycemia. RESULTS: The rate of major hypoglycemia
      decreased in patients with type 1 diabetes--the incidence rate ratio (IRR) was
      0.14 for daytime and 0.03 for nocturnal episodes (P <0.0001) and did not change
      in patients with type 2 diabetes. The rate of minor episodes decreased in
      patients with type 1 diabetes (IRR = 0.44 for daytime and IRR = 0.24 for
      nocturnal episodes, P <0.0001) and in patients with type 2 diabetes (IRR= 0.57, P
      <0.0001 for daytime and IRR = 0.89, P <0.05 for nocturnal episodes). HbA1c
      decreased by 1.28 +/- 1.64% in type 1 and 1.25 +/- 1.10% in type 2 diabetes (both
      P <0.0001). Self-measured fasting and postprandial blood glucose levels were
      significantly lower at the final visit compared with baseline, irrespective of
      diabetes type. CONCLUSIONS: In clinical practice, treatment with insulin aspart
      in basal-bolus regimen is associated with low risk of hypoglycemia and leads to a
      significant improvement in glucose control, irrespective of diabetes type.

PMID- 21102381
TI  - How should we diagnose spondyloarthritis according to the ASAS classification
      criteria: a guide for practicing physicians.
AB  - The Assessment of SpondyloArthritis International Society (ASAS) group has
      recently developed criteria to classify patients with axial SpA with or without
      radiographic sacroiliitis, and criteria to classify patients with peripheral SpA.
      The ASAS axial criteria consist of 2 arms and can be applied in patients with
      back pain (>3 months almost every day). In one arm, imaging (radiographs and
      magnetic resonance imaging [MRI]) has an important role, in the other arm--HLA
      B27. MRI can detect active inflammation and structural damage associated with
      SpA. According to the ASAS axial SpA criteria, patients with chronic back pain
      aged less than 45 years at onset can be classified as having axial SpA if
      sacroiliitis on imaging (radiographs or MRI) plus 1 further SpA feature are
      present, or if HLA-B27 plus 2 further SpA features are present. The ASAS
      peripheral criteria can be applied in patients with peripheral arthritis (usually
      asymmetric arthritis predominantly involving the lower limbs), enthesitis, or
      dactylitis. Patients can be classified as having peripheral SpA if 1 of the
      following features is present: uveitis, HLA-B27, preceding genitourinary or
      gastrointestinal infection, psoriasis, inflammatory bowel disease, sacroiliitis
      on imaging (radiographs or MRI), or if 2 of the following features besides the
      entry feature are present: arthritis, enthesitis, dactylitis, inflammatory back
      pain, or a positive family history of SpA.

PMID- 21102382
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is
      an advance in bronchoscopy. It is a staging tool for nonsmall cell lung cancer
      (NSCLC) but also allows diagnosis of unexplained mediastinal lymphadenopathy due
      to malignant and benign disease. It is a minimally invasive procedure that is
      used to stage suspected NSCLC with hilar nodes, discrete N2 or N3 disease, or
      bulky mediastinal disease. After a negative EBUS-TBNA result, if the pretest
      probability of lung cancer is high, a mediastinoscopy is still recommended,
      although in the light of recent trial data this is likely to change. EBUS-TBNA is
      expensive, which may limit its development in resource-rationed health care
      systems. Conventional (without ultrasound) transbronchial needle aspiration
      (TBNA) still has a useful role in lung cancer staging, especially where EBUS-TBNA
      is not available; it can help avoid unnecessary mediastinoscopies.

PMID- 21102383
TI  - Efficacy of physical therapy methods in airway clearance in patients with chronic
      obstructive pulmonary disease: a critical review.
AB  - Multiplicity and variety of chest physical therapy (CPT) methods for increasing
      bronchial clearance in patients with chronic obstructive pulmonary disease (COPD)
      require an assessment of validity and reliability of the available clinical
      evidence. The aim of the review was to evaluate publications on CPT in COPD
      patients and to establish the basis (objective criteria) on which given methods
      and techniques are recommended or refuted. Systematic reviews, narrative reviews,
      and clinical practice guidelines, published in English between January 1, 2000
      and July 1, 2010, were identified from the PubMed/MEDLINE and Cochrane (DARE,
      CRD, The Cochrane Airways Review Group Register) databases. The PEDro and SIGN
      scales were used to assess the quality and grade of recommendations for selected
      papers. Generally, the papers that we identified were based on small studies,
      limited to short-term outcomes, mostly using crossover designs, and rarely
      including sham therapy. Recommendations from clinical guidelines were mainly
      grade C or D. Health-related quality-of-life analyses, including working and
      exercise capacity, are lacking. The evidence from the studies in patients with
      cystic fibrosis cannot be directly extrapolated to COPD subjects. Despite the
      lack of convincing evidence, clinical practice supports the value of CPT in COPD.
      However, when making a clinical decision, potential side effects should be
      considered.

PMID- 21102384
TI  - Notice of redundant publications.

PMID- 21102385
TI  - Should we be worried about disturbed sympathovagal balance during laparoscopic
      cholecystectomy?

PMID- 21102386
TI  - Permissive mild to moderate hyperglycemia is safer for damaged brains.

PMID- 21102387
TI  - The effects of pneumoperitoneum and head-up position on heart rate variability
      and QT interval dispersion during laparoscopic cholecystectomy.
AB  - BACKGROUND: The aim of the study was to evaluate the effects of pneumoperitoneum
      and head-up position on autonomic cardiac function changes during inhalational or
      total intravenous anesthesia by using the analysis of QT dispersion and heart
      rate variability (HRV). METHODS: In this prospective, single-blind study, 30
      patients scheduled for elective laparoscopic cholecystectomy were randomly
      divided in two groups: a sevoflurane-based inhalational anesthesia group (N=15)
      and an intravenous anesthesia group with propofol (N=15). Propofol 2.0 mg/kg-1
      and cisatracurium 0.15 mg/kg-1 during induction of anesthesia and Remifentanil as
      titrated infusion for analgesia were used in both groups. Pneumoperitoneum was
      established at 12 mmHg with patients in the supine position. ECG was recorded
      before the induction of anesthesia; 1 and 3 min after pneumoperitoneum (supine
      position); 1 and 3 min after shifting the patient to a head-up position (HUP) of
      60 degrees; after abdominal deflation; and after awakening. RR interval, QT
      interval, corrected QT interval (QTc), QT interval dispersion (QTD), corrected QT
      interval dispersion (QTcD), low-frequency power (LF), high-frequency power (HF)
      and LF/HF ratio were recorded. RESULTS: The LF/HF ratio increased significantly
      after 3 min HUP in the SEVO group (P<0.05). QTD and QTcD increased significantly
      at 3 min after abdominal insufflation and at 1 and 3 min after HUP in both groups
      (P<0.05). CONCLUSION: Statistically significant increases of QTD and QTcD
      occurred during pneumoperitoneum and HUP, regardless of the anesthetic techniques
      used. In patients receiving inhalational anesthesia, the LF/HF ratio increased
      significantly after HUP.

PMID- 21102388
TI  - Positive end-expiratory pressure, prone positioning, and activated protein C: a
      critical review of meta-analyses.
AB  - The results of meta-analyses on the effectiveness of high positive end-expiratory
      pressure (PEEP) and prone positioning in acute lung injury (ALI)/acute
      respiratory distress syndrome (ARDS) are not consistent. In addition, the meta
      analyses on the activated protein C in patients with sepsis combine trials with
      discordant results. Therefore, the aim of this paper was to give a critical
      review of these meta-analyses. All relevant meta-analyses were identified by a
      computerized search of PubMed using combinations of the following terms: acute
      lung injury, acute respiratory distress syndrome, positive end-expiratory
      pressure, mechanical ventilation, prone position, drotrecogin, activated protein
      C, sepsis, and septic patients. A high level of PEEP and prone ventilation was
      shown to reduce the mortality in patients with severe acute hypoxemic respiratory
      failure. Although the evidence for the efficacy of activated protein C is not
      conclusive, it should be considered in patients that are at a high risk for death
      without any contraindications related to bleeding risk. Meta-analysis models can
      be very useful for clinical decisions if they include all of the similar papers
      on a medical topic and are correct from the methodological point of view;
      however, these results must be checked by a careful and well-informed reader.

PMID- 21102389
TI  - Pharmacogenetics and postoperative pain: a new approach to improve acute pain
      management.
AB  - Acute postoperative pain is a complex phenomenon that baffles the staff involved
      in both its prevention and treatment. Acute postoperative pain varies even among
      patients who underwent the same type of surgery, and it is now known to be caused
      by different factors, including genetic background. This review will focus on the
      most important genes correlated with inter-patient differences in both pain
      sensitivity and analgesic response. Pain therapy is often administered to
      patients who are also taking other types of medication; therefore, drug
      interactions must be considered. A genetic analysis of receptors, of drug
      transporters, and of metabolizing enzymes may be needed to establish the
      effective doses of each drug in the individual patient to prevent side effects
      and also to achieve pain relief in a shorter period of time, which may prevent
      acute pain from becoming chronic. The etiology of chronic pain has not been
      elucidated yet, but we know that genetic predisposition comes into play, together
      with other clinical factors. Clinical trials including genetic analysis could be
      extremely useful in optimizing the management of postoperative pain therapy.

PMID- 21102390
TI  - Limitations of volumetric indices obtained by trans-thoracic thermodilution.
AB  - Transthoracic thermodilution (TTT) measures cardiac output without the need for
      right heart catheterization. In addition, two volumetric hemodynamic indices have
      been derived from the mathematical analysis of the TTT curve: the global end
      diastolic volume (a quantitative measure of cardiac preload) and the
      extravascular lung water volume (a quantitative measure of pulmonary edema).
      Despite the undeniable appeal of these two novel parameters, uncertainty exists
      regarding both the validity of their mathematical derivation and their
      physiological significance. This concise review attempts to discuss such
      concerns.

PMID- 21102391
TI  - Fungal infections in ICU patients: epidemiology and the role of diagnostics.
AB  - Invasive fungal infections (IFIs) are on the increase not only among oncology and
      transplant patients but also among patients admitted to intensive care units
      (ICU). The rise in ICU IFIs can be attributed to the growing use of complex
      surgical procedures, invasive medical devices, and long-term, broad-spectrum
      antibiotic therapy. The majority of these life-threatening infections are caused
      by the well-known opportunistic pathogens Candida albicans and Aspergillus
      fumigatus, but new opportunistic pathogens, including yeast-like and other
      filamentous fungi, have emerged as additional causes. Invasive Candida
      infections, particularly candidemia, represent the most common IFI in critically
      ill patients. The species that cause candidemia markedly differ in their
      responses to antifungal drugs; for this reason, therapy must be tailored to the
      susceptibility characteristics of the infectious agent. Candidemia caused by non
      albicans Candida species is increasing worldwide, and these infections are
      generally associated with high mortality rates, particularly bloodstream
      infections caused by C. krusei, which is innately resistant to fluconazole, or C.
      glabrata, which easily develops azole resistance. Although invasive yeast
      infections can be considered the most important causes of morbidity and mortality
      in ICU patients, pulmonary aspergillosis has recently emerged as an additional
      complication. Diagnosis of IFIs can be achieved using conventional approaches
      (microscopy, culture, and serology) and newer methods, including antigen
      detection and polymerase chain reaction (PCR) assays. Because most of the
      conventional approaches lack sensitivity, antigen detection and PCR assays could
      represent a valid alternative; however, these procedures need to be standardized
      and evaluated in a large number of patients.

PMID- 21102392
TI  - Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure
      and acute kidney injury on sustained low-efficiency dialysis (SLED).
AB  - We report on a patient with biliary sepsis due to Vancomycin-resistant
      Enterococcus faecium (VRE) treated with linezolid (LNZ), who had both hepatic
      failure and acute kidney injury requiring daily sustained low-efficiency dialysis
      (SLED), a new intermittent, prolonged diffusive modality of renal replacement
      therapy for ICU patients. Following cholecystostomy and peritoneal drain
      insertion, serum, bile and peritoneal fluid serial samples were simultaneously
      collected for LNZ concentration measurement (chromatography/mass spectrometry).
      Unusually high serum antibiotic levels (20 mg/L or more) were achieved as early
      as 36 hours since the start of LNZ administration, owing to relatively low
      hepatic clearance. Serum LNZ leveled off after commencing SLED, apparently
      reaching steady state levels. The lowest values of Cmin in bile was 5.86 mg/L;
      the average serum and bile AUC0-12 over the observation period were 204 mg/L*h
      and 276 mg/L*h, with a AUC0-24/MIC ratio of 227 h and 307 h, respectively. The
      excellent biliary pharmacodynamic exposure suggests that standard-dose LNZ might
      represent a valuable choice in severe biliary infection, even in the presence of
      hepatic failure, when the patients receive highly efficient modalities of renal
      replacement therapy.

PMID- 21102393
TI  - Gram meter and the right ventricular stroke work.

PMID- 21102394
TI  - The Helsinki Declaration on Patient Safety in Anesthesiology: a way forward with
      the European Board and the European Society of Anesthesiology.
AB  - Anesthesiology, which includes anaesthesia, perioperative care, intensive care
      medicine, emergency medicine and pain therapy, is acknowledged as the leading
      medical specialty in addressing issues of patient safety, but there is still a
      long way to go. Several factors pose hazards in Anesthesiology, like increasingly
      older and sicker patients, more complex surgical interventions, more pressure on
      throughput, as well as new drugs and devices. To better design educational and
      research strategies to improve patient safety, the European Board of
      Anesthesiology (EBA) and the European Society of Anesthesiology (ESA) have
      produced a blueprint for patient safety in Anesthesiology. This document, to be
      known as the Helsinki Declaration on Patient Safety in Anesthesiology, was
      endorsed together with the World Health Organization (WHO), the World Federation
      of Societies of Anesthesiologists (WFSA), and the European Patients' Federation
      (EPF) at the Euroanaesthesia meeting in Helsinki in June 2010. It was signed by
      several Presidents of National Anesthesiology Societies as well as other
      stakeholders. The Helsinki Declaration on Patient Safety in Anesthesiology
      represents a shared European view of what is necessary to improve patient safety,
      recommending practical steps that all anesthesiologists can include in their own
      clinical practice. The Italian Society of Anaesthesia, Analgesia, Reanimation and
      Intensive Care (SIAARTI) is looking forward to continuing work on "patient
      safety" issues in Europe, and to cooperating with the ESA in the best interest of
      European patients.

PMID- 21102395
TI  - Selective decontamination of the digestive tract as infection prevention in the
      critically ill. A level 1 evidence-based strategy.
AB  - Selective decontamination of the digestive tract (SDD) evolved into evidence
      based medicine as a tool to prevent infections in critically ill patients. It
      significantly reduces mortality, pneumonia, bloodstream infections and the onset
      of resistance if the full four-component regimen is used. The use of only oral
      decontamination may reduce the incidence of pneumonia, but it has no significant
      impact on mortality. Moreover, the full SDD protocol significantly reduces the
      fecal carriage of multiresistant aerobic Gram-negative bacteria, whereas oral
      decontamination only is associated with increased carriage of multiresistant
      aerobic Gram-negative bacilli.

PMID- 21102396
TI  - Levobupivacaine versus bupivacaine: is there as winner?

PMID- 21102397
TI  - Comments on tracheal intubation using the mobile C-MAC videolaryngoscope or
      direct laryngoscopy in patients with a simulated difficult airway.

PMID- 21102398
TI  - Use of corticosteroids in septic shock.
AB  - Corticosteroids are potent anti-inflammatory agents whose use has been life
      saving in many diseases. Thus, it makes intuitive sense to use corticosteroids in
      septic shock, a disease where the inflammatory response is vigorously activated.
      Early studies examining the usage of corticosteroids in septic shock did not show
      any benefit, however, these studies administered very large doses. More recently,
      attention has been focused on the use of lower doses of corticosteroids to treat
      relative adrenal insufficiency in septic shock; however, results have been
      controversial. Multi-center double blinded, randomized trials further added to
      the controversy without completely clarifying the issue. Moreover, the use of
      corticosteroids in critical illness must balance potential benefits with minimal
      side effects, however even such issues remain debatable as some studies show no
      untoward harm while other find the opposite. This review examines the use of
      corticosteroids in septic shock, discusses some of the shortcomings of the major
      clinical trials and outlines the most recent recommendations.

PMID- 21102399
TI  - Oropharyngeal CPAP: a new CPAP technique for newborns with nasal anomaly.

PMID- 21102400
TI  - Time to wake up the patients in the ICU: a crazy idea or common sense?
AB  - With the first generation of ventilators, it was often necessary to sedate
      patients to avoid dyssynchrony between patient and ventilator. The standard
      treatment of patients in need of mechanical ventilation has therefore
      traditionally included sedation. Modern ventilators are able to simulate the
      patients breathing efforts to a higher degree, and therefore, deep sedation is no
      longer necessary. In the last decade, support has grown for a reduction in the
      use of sedation. The focus has been placed on the correlation between the depth
      of sedation and the length of mechanical ventilation. It has been shown that a
      daily wake up trial reduced the time that patients were dependent on mechanical
      ventilation. Additionally, it has been shown that combining both a spontaneous
      breathing trial and a daily wake up trial reduced the mechanical ventilation time
      compared to a spontaneous breathing trial alone. We have recently shown in a
      randomized study that the use of no sedation, compared to the standard treatment
      with sedation and a daily wake up trial, reduced the time that patients required
      mechanical ventilation, the length of the patients' stay in the intensive care
      unit, and the total length of the hospital stay. All evidence indicates that the
      use of sedative drugs should be reduced, patients should be mobilized, and each
      patient's needs should be evaluated on a daily basis to optimize the care of each
      individual patient.

PMID- 21102401
TI  - Right ventricular function in children with severe respiratory syncytial virus
      (RSV) bronchiolitis.
AB  - BACKGROUND: Previous studies have demonstrated the development of myocardial
      damage and hepatitis in children with severe respiratory syncytial virus (RSV)
      infection. The aim of this study was to assess right ventricular function in
      children with severe RSV disease and to investigate an association with disease
      severity, myocardial damage, and hepatitis. METHODS: This was a prospective
      observational study performed at a 20-bed regional multidisciplinary tertiary
      pediatric intensive care unit (PICU) in a university-affiliated children's
      hospital. Pulse wave Doppler echocardiographic assessments with a calculation of
      the right ventricular function (Tei index), left ventricular ejection fraction
      and diameters, cardiac troponin T levels, transaminase and C-reactive protein
      levels were performed at admission on consecutive children who were ventilated
      and diagnosed with a severe RSV infection and without congenital heart disease.
      RESULTS: Thirty-four ventilated children with confirmed RSV bronchiolitis were
      enrolled. The median age was 1.4 months (range 0.4-11.7), and the median length
      of ventilation was 5 days (range 2-10). Seven (20%) infants had an elevated right
      ventricular Tei index indicating reduced right ventricular function. Left
      ventricular function as well as C-reactive protein and transaminase levels were
      not different between patients with and without an elevated right ventricular Tei
      index. Cardiac troponin T was elevated in 14 patients (41%): 3/7 with an elevated
      and 11/27 with a normal Tei index (P=1). Ventilation and oxygenation indices and
      the duration of mechanical ventilation were not different between the two groups.
      CONCLUSION: A raised right ventricular Tei index, consistent with reduced right
      ventricular function, was observed in severe RSV disease, but the degree of
      dysfunction was not related to the level of biochemical myocardial or hepatic
      damage or level of respiratory support.

PMID- 21102402
TI  - OROS(r) hydromorphone in chronic pain management: when drug delivery technology
      matches clinical needs.
AB  - The osmotic-controlled release oral delivery system (OROS(r)) is an innovative
      drug delivery technology that uses osmotic pressure as the driving force to
      deliver pharmacotherapies in many therapeutic areas. In chronic pain management
      requiring long-term therapy, pharmaceutical technologies that ensure the
      controlled release of analgesic medications are imperative. In addition, once
      daily formulations ensure better patient compliance to prescribed therapies.
      Hydromorphone was the first opioid to be formulated as a once-daily preparation
      using OROS(r) technology. The purpose of this review is to discuss the
      application of OROS(r) technology in the field of chronic pain management and to
      examine clinical trial results for OROS(r) Hydromorphone. OROS(r) hydromorphone
      ensures the constant delivery of hydromorphone over a 24-hour period, and its
      pharmacokinetic profile is only minimally affected by food and alcohol. Dose
      conversion studies have shown that patients with chronic pain can be easily
      switched from previous opioid therapies to OROS(r) hydromorphone without a loss
      of pain control. These studies support the clinical utility of the 5:1 ratio used
      for the conversion of oral morphine to oral OROS(r) hydromorphone. Furthermore,
      once-daily OROS(r) hydromorphone has been shown to be effective in patients with
      chronic cancer and non-cancer pain, and it provides similar pain relief to SR
      morphine and ER oxycodone. In chronic pain management, OROS(r) products can
      result in more stable drug concentrations, reduced dosing frequency and an
      improved safety profile.

PMID- 21102403
TI  - The distance from the skin to the epidural and subarachnoid spaces in parturients
      scheduled for caesarean section.
AB  - BACKGROUND: The purpose of this study was to measure the skin to epidural space
      distance (SED), the skin to subarachnoid space distance (SSD) and the epidural to
      subarachnoid space distance (ESD) at the L3-4 interspace in parturients scheduled
      for caesarean section (CS) and to investigate whether any correlations exist
      between these distances and various physical and anthropometric parameters.
      METHODS: This study consisted of 332 parturients scheduled for CS. The epidural
      space was identified by noting the loss of resistance to air at the L3-4
      intervertebral space with a Tuohy needle, thus permitting measurement of the SED.
      The spinal needle was introduced through the Tuohy needle and, after
      identification of the subarachnoid space, was locked in the epidural needle. The
      distance between the tip of the Tuohy needle and tip of spinal needle (ESD) was
      recorded. This number was added to the SED to obtain the SSD value. RESULTS: Mean
      values +/- standard deviations for SED, SSD and ESD were 5.6 +/- 1.6 cm, 6.5 +/-
      1.2 cm and 0.9 +/- 0.5 cm, respectively. Statistically significant correlations
      were observed between SED, SSD and ESD with body mass index and body weight of
      the parturients, as well as between the SED and the parturient's height.
      Furthermore, a significant negative correlation was observed between the ESD and
      gestational age. Finally, a significant correlation existed between the SSD and
      ESD. CONCLUSION: Measurements of SED, SSD and ESD in parturients and the
      correlations between these distances to various physical and anthropometric
      parameters may be of potential value for combined spinal-epidural anesthesia
      (CSEA) in parturients scheduled for CS.

PMID- 21102404
TI  - Mortality among patients with tuberculosis and associations with HIV status ---
      United States, 1993-2008.
AB  - Worldwide, tuberculosis (TB) incidence increased from 125 cases per 100,000
      population in 1990 to 142 cases per 100,000 population in 2004, primarily because
      of the human immunodeficiency virus (HIV) epidemic. Persons with HIV are at
      increased risk for TB disease, and those with TB have a high risk for death. This
      is documented most clearly in resource-limited settings, where limited access to
      antiretroviral therapy (ART) and other health-care services contribute to the
      elevated mortality. The impact of HIV on patients with TB is less clear in
      resource-rich nations such as the United States. To understand the impact of HIV
      on the risk for death during TB treatment in the United States, data were
      analyzed for all culture-positive patients with TB from 1993 to 2008, and the
      proportion that died was determined and stratified by HIV test result. Mortality
      data were restricted to patients reported before 2007. The proportion of all
      patients with TB who died during TB treatment decreased from 2,445 of 13,629
      (18%) in 1993 to 682 of 7,578 (9%) in 2006. Among patients with TB and HIV, 950
      of 2,337 (41%) died during treatment in 1993; this proportion declined to 131 of
      663 (20%) in 2006. The proportion of patients with TB and HIV who received their
      TB diagnosis postmortem dropped from 191 of 2,927 (7%) in 1993 to 32 of 768 (4%)
      in 2006; 624 of 10,468 (6%) persons with TB and unknown HIV status received their
      TB diagnosis postmortem in 1993, and this proportion did not decline. Further
      reductions in mortality can be achieved by enhanced TB/HIV program collaboration
      and service integration.

PMID- 21102405
TI  - HIV testing and treatment among tuberculosis patients --- Kenya, 2006-2009.
AB  - In resource-limited settings, high case-fatality rates are seen among
      tuberculosis (TB) patients with human immunodeficiency virus (HIV) infection,
      especially during the early months of TB treatment. HIV prevalence among TB
      patients has been estimated to be as high as 80%--90% in some areas of sub
      Saharan Africa. In 2004, the World Health Organization (WHO) recommended
      increasing collaboration between HIV and TB programs. Since then, many countries,
      including Kenya, have worked to increase TB/HIV collaborative activities. In
      2005, the Kenya Division of Leprosy, Tuberculosis, and Lung Disease (DLTLD) added
      questions regarding HIV testing and treatment to the existing TB surveillance
      system.* This report summarizes HIV data collected from Kenya's extended TB
      surveillance system during 2006--2009. During this period, HIV testing among TB
      patients increased from 60% in 2006 to 88% in 2009, and the prevalence of HIV
      infection among TB patients tested decreased from 52% to 44%. In 2009, 92% of HIV
      infected TB patients received cotrimoxazole prophylaxis for the prevention of
      opportunistic infections. Although these data highlight the increase in HIV
      services provided to TB patients, only 34% of HIV-infected TB patients started
      antiretroviral therapy (ART) while being treated for TB. Innovative interventions
      are needed to increase HIV treatment among TB patients in Kenya, especially
      considering the 2009 WHO guidelines recommending that all HIV-infected TB
      patients be started on ART as soon as possible, regardless of CD4 count. Although
      these guidelines have not yet been implemented in Kenya, officials are working to
      identify methods of increasing access to ART for TB patients.

PMID- 21102406
TI  - Racial disparities in smoking-attributable mortality and years of potential life
      lost --- Missouri, 2003-2007.
AB  - An estimated 443,000 deaths in the United States occur each year as a result of
      cigarette smoking and exposure to secondhand smoke. These deaths cost the nation
      approximately $97 billion in lost productivity and $96 billion in health-care
      costs. During 2000-2004 in Missouri, smoking caused 9,600 deaths, 132,000 years
      of potential life lost (YPLL), $2.4 billion in productivity losses, and $2.2
      billion in smoking-related health-care expenditures annually. To limit the
      adverse health consequences of tobacco use, states implement comprehensive
      tobacco control programs that identify disparities among population groups and
      target those disproportionately affected by tobacco use. This report compares the
      public health burden of smoking among whites and blacks in Missouri by estimating
      the number of smoking-attributable deaths and YPLL in these population subgroups
      during 2003-2007. The findings indicate that the average annual smoking
      attributable mortality (SAM) rate in the state was 18% higher for blacks (338
      deaths per 100,000) than for whites (286 deaths per 100,000). The relative
      difference in smoking-attributable mortality rates between blacks and whites was
      larger for men (28%) than women (11%). For Missouri, these estimates provide an
      important benchmark for measuring the success of tobacco control programs in
      decreasing the burden of smoking-related diseases in these populations and
      reaffirm the need for full implementation of the state's comprehensive tobacco
      control program.

PMID- 21102407
TI  - Surveillance of screening-detected cancers (colon and rectum, breast, and cervix)
      - United States, 2004-2006.
AB  - PROBLEM/CONDITION: Population-based screening is conducted to detect diseases or
      other conditions in persons before symptoms appear; effective screening leads to
      early detection and treatment, thereby reducing disease-associated morbidity and
      mortality. Based on systematic reviews of the evidence of the benefits and harms
      and assessments of the net benefit of screening, the U.S. Preventive Services
      Task Force (USPSTF) recommends population-based screening for colon and rectum
      cancer, female breast cancer, and uterine cervix cancer. Few publications have
      used national data to examine the stage at diagnosis of these screening-amenable
      cancers. REPORTING PERIOD COVERED: 2004-2006. DESCRIPTION OF SYSTEMS: Data were
      obtained from cancer registries affiliated with CDC's National Program of Cancer
      Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology,
      and End Results (SEER) program. Combined data from the NPCR and SEER programs
      provide the best source of information on national population-based cancer
      incidence. Data on cancer screening were obtained from the Behavioral Risk Factor
      Surveillance System. This report provides stage-specific cancer incidence rates
      and screening prevalence by demographic characteristics and U.S. state. RESULTS:
      Approximately half of colorectal and cervical cancer cases and one third of
      breast cancer cases were diagnosed at a late stage of disease. Incidence rates of
      late-stage cancer differed by age, race/ethnicity, and state. Incidence rates of
      late-stage colorectal cancer increased with age and were highest among black men
      and women. Incidence rates of late-stage breast cancer were highest among women
      aged 60-79 years and black women. Incidence rates of late-stage cervical cancer
      were highest among women aged 50-79 years and Hispanic women. The percentage of
      persons who received recommended screening differed by age, race/ethnicity, and
      state. INTERPRETATION: Differences in late-stage cancer incidence rates might be
      explained partially by differences in screening use. PUBLIC HEALTH ACTION: The
      findings in this report emphasize the need for ongoing population-based
      surveillance and reporting to monitor late-stage cancer incidence trends.
      Screening can identify colorectal, cervical, and breast cancers in earlier and
      more treatable stages of disease. Multiple factors, including individual
      characteristics and health behaviors as well as provider and clinical systems
      factors, might account for why certain populations are underscreened. Cancer
      control planners, including comprehensive cancer-control programs, can use late
      stage cancer incidence and screening prevalence data to identify populations that
      would benefit from interventions to increase screening utilization and to monitor
      performance of early detection programs.

PMID- 21102408
TI  - CSN complex controls the stability of selected synaptic proteins via a torsinA
      dependent process.
AB  - DYT1 dystonia is caused by an autosomal dominant mutation that leads to a
      glutamic acid deletion in torsinA (TA), a member of the AAA+ ATPase superfamily.
      In this study, we identified a novel-binding partner of TA, the subunit 4 (CSN4)
      of CSN signalosome. TA binds CSN4 and the synaptic regulator snapin in
      neuroblastoma cells and in brain synaptosomes. CSN4 and TA are required for the
      stability of both snapin and the synaptotagmin-specific endocytic adaptor stonin
      2, as downregulation of CSN4 or TA reduces the levels of both proteins. Snapin is
      phosphorylated by the CSN-associated kinase protein kinase D (PKD) and its
      expression is decreased upon PKD inhibition. In contrast, the stability of stonin
      2 is regulated by neddylation, another CSN-associated activity. Overexpression of
      the pathological TA mutant (DeltaE-TA) reduces stonin 2 expression, causing the
      accumulation of the calcium sensor synaptotagmin 1 on the cell surface. Retrieval
      of surface-stranded synaptotagmin 1 is restored by overexpression of stonin 2 in
      DeltaE-TA-expressing cells, suggesting that the DYT1 mutation compromises the
      role of TA in protein stabilisation and synaptic vesicle recycling.

PMID- 21102409
TI  - Novel role and mechanism of protein inhibitor of activated STAT1 in spatial
      learning.
AB  - By using differential display PCR, we have previously identified 98 cDNA
      fragments from rat dorsal hippocampus, which are expressed differentially between
      the fast learners and slow learners from water-maze learning task. One cDNA
      fragment, which showed a higher expression level in fast learners, encodes the
      rat protein inhibitor of activated STAT1 (pias1) gene. Spatial training induced a
      significant increase in PIAS1 expression in rat hippocampus. Transient
      transfection of the wild-type (WT) PIAS1 plasmid to CA1 neurons facilitated,
      whereas transfection of PIAS1 siRNA impaired spatial learning in rats. Meanwhile,
      PIAS1WT increased STAT1 sumoylation, decreased STAT1 DNA binding and decreased
      STAT1 phosphorylation at Tyr-701 associated with spatial learning facilitation.
      But PIAS1 siRNA transfection produced an opposite effect on these measures
      associated with spatial learning impairment. Further, transfection of STAT1
      sumoylation mutant impaired spatial acquisition, whereas transfection of STAT1
      phosphorylation mutant blocked the impairing effect of PIAS1 siRNA on spatial
      learning. In this study, we first demonstrate the role of PIAS1 in spatial
      learning. Both posttranslational modifications (increased sumoylation and
      decreased phosphorylation) mediate the effect of PIAS1 on spatial learning
      facilitation.

PMID- 21102410
TI  - The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF
      interaction and specificity toward the pre-mRNA.
AB  - Star-PAP is a poly (A) polymerase (PAP) that is putatively required for 3'-end
      cleavage and polyadenylation of a select set of pre-messenger RNAs (mRNAs),
      including heme oxygenase (HO-1) mRNA. To investigate the underlying mechanism,
      the cleavage and polyadenylation of pre-mRNA was reconstituted with nuclear
      lysates. siRNA knockdown of Star-PAP abolished cleavage of HO-1, and this
      phenotype could be rescued by recombinant Star-PAP but not PAPalpha. Star-PAP
      directly associated with cleavage and polyadenylation specificity factor (CPSF)
      160 and 73 subunits and also the targeted pre-mRNA. In vitro and in vivo Star-PAP
      was required for the stable association of CPSF complex to pre-mRNA and then CPSF
      73 specifically cleaved the mRNA at the 3'-cleavage site. This mechanism is
      distinct from canonical PAPalpha, which is recruited to the cleavage complex by
      interacting with CPSF 160. The data support a model where Star-PAP binds to the
      RNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines
      cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs.

PMID- 21102412
TI  - Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms
      of the pancreas.
AB  - Claudin-4, encoding a protein for tight junction formation and function, is
      highly overexpressed in pancreatic ductal adenocarcinoma and is also associated
      with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms
      of the pancreas. However, the expression pattern of claudin-4 during neoplastic
      progression of intraductal papillary mucinous neoplasms remains unknown. Using
      quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a
      panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffin-embedded
      tissues from 80 patients with intraductal papillary mucinous neoplasms of
      different histological grades and papillary subtypes. Increased expression of
      claudin-4 was confirmed in all the pancreatic cancer cell lines tested as
      compared with normal ductal epithelial cells and fibroblast cultures. The claudin
      4 expression was significantly higher in high-grade intraductal papillary
      mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade
      intraductal papillary mucinous neoplasms (adenoma) (P<0.0001). In addition,
      claudin-4 mRNA levels were significantly higher in intestinal-type intraductal
      papillary mucinous neoplasms than in non-intestinal-type intraductal papillary
      mucinous neoplasms based on papillary subclassification (P<0.0001). Our findings
      suggest that claudin-4 expression is associated with neoplastic progression of
      intraductal papillary mucinous neoplasms and, especially, with a distinct pathway
      to intestinal differentiation.

PMID- 21102411
TI  - Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto
      its receptor Pex3p.
AB  - Peroxisomes require peroxin (Pex) proteins for their biogenesis. The interaction
      between Pex3p, which resides on the peroxisomal membrane, and Pex19p, which
      resides in the cytosol, is crucial for peroxisome formation and the post
      translational targeting of peroxisomal membrane proteins (PMPs). It is not known
      how Pex3p promotes the specific interaction with Pex19p for the purpose of PMP
      translocation. Here, we present the three-dimensional structure of the complex
      between a cytosolic domain of Pex3p and the binding-region peptide of Pex19p. The
      overall shape of Pex3p is a prolate spheroid with a novel fold, the 'twisted six
      helix bundle.' The Pex19p-binding site is at an apex of the Pex3p spheroid. A 16
      residue region of the Pex19p peptide forms an alpha-helix and makes a contact
      with Pex3p; this helix is disordered in the unbound state. The Pex19p peptide
      contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21,
      Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome
      biogenesis.

PMID- 21102413
TI  - Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health
      Organization classification.
AB  - Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic
      proliferation of erythroblasts. Given recent incorporation of molecular genetic
      findings and clinical features in the revised 2008 World Health Organization
      classification scheme of acute myeloid leukemia, we questioned if PEL still
      remains as a distinct subtype of acute myeloid leukemia. In this retrospective
      study, we identified 18 cases of acute leukemia with morphologic and
      immunophenotypic features of PEL. Following the current World Health Organization
      classification algorithm, these cases were classified as: 13 acute myeloid
      leukemia with myelodysplasia-related changes, 3 therapy-related acute myeloid
      leukemia, and 1 chronic myelogenous leukemia blast crisis, and one unclassifiable
      due to insufficient clinical information. All 16 cases with cytogenetic data
      harbored an extremely complex karyotype and the median overall survival of the 18
      patients was 3 months (range, 1-7 months). This survival was significantly
      shorter than that of patients with acute erythroid leukemia, erythroid/myeloid
      subtype, or acute myeloid leukemia with myelodysplasia-related changes with
      erythroid predominance (P<0.001). PEL is characterized as a neoplastic erythroid
      hyperproliferation with maturation arrest. E-cadherin emerged as the most
      sensitive and specific marker for immature erythroblasts, and was helpful in
      distinguishing PEL from other erythroid proliferations. Our study showed that the
      criteria for acute myeloid leukemia in the 2008 World Health Organization system
      facilitate reclassification of PEL cases into other acute myeloid leukemia
      categories, mainly of acute myeloid leukemia with myelodysplasia-related changes.
      These new assigned categories fail to capture the distinct features of PEL, where
      the phenotype of PEL correlates with a very complex karyotype and an extremely
      aggressive clinical course.

PMID- 21102414
TI  - Downregulation of ASPP1 in gestational trophoblastic disease: correlation with
      hypermethylation, apoptotic activity and clinical outcome.
AB  - Gestational trophoblastic disease encompasses a spectrum of trophoblastic lesions
      including true neoplasms such as choriocarcinomas and the potentially malignant
      hydatidiform moles, which may develop persistent disease requiring chemotherapy.
      ASPP1, a member of apoptosis-stimulating proteins of p53 (ASPPs), is a
      proapoptotic protein that can stimulate apoptosis through its interaction with
      p53. We evaluated the promoter methylation and expression profiles of ASPP1 in
      different trophoblastic tissues and its in vitro functional effect on two
      choriocarcinoma cell lines, namely JEG-3 and JAR. Significant downregulation of
      ASPP1 mRNA and protein levels was demonstrated in hydatidiform moles and
      choriocarcinomas, when compared with normal placentas by quantitative-PCR and
      immunohistochemistry. The ASPP1 mRNA level was significantly correlated with its
      hypermethylation status, evaluated with methylation-specific PCR, in placenta and
      gestational trophoblastic disease samples (P=0.024). Moreover, lower ASPP1
      immunoreactivity was shown in hydatidiform moles that progressed to persistent
      gestational trophoblastic neoplasms than in those that regressed (P=0.045). A
      significant correlation was also found between expression of ASPP1 and
      proliferative indices (assessed by Ki67 and MCM7), apoptotic activity (M30
      CytoDeath antibody), p53 and caspase-8 immunoreactivities. An in vitro study
      showed that ectopic expression of ASPP1 could trigger apoptosis through intrinsic
      and extrinsic pathways as indicated by an increase in cleaved caspase-9 and Fas
      ligand protein expression. The latter suggests a hitherto unreported novel link
      between ASPP1 and the extrinsic pathway of apoptosis. Our findings suggest that
      downregulation of ASPP1 by hypermethylation may be involved in the pathogenesis
      and progress of gestational trophoblastic disease, probably through its effect on
      apoptosis.

PMID- 21102415
TI  - Molecular clustering based on ERalpha and EIG121 predicts survival in high-grade
      serous carcinoma of the ovary/peritoneum.
AB  - Assessment of estrogen receptor (ER) expression by immunohistochemistry has
      yielded inconsistent results as a prognostic indicator in ovarian carcinoma. In
      breast and endometrial carcinomas, panels of estrogen-induced genes have shown
      improved prognostic capability over the use of ER immunohistochemistry alone. For
      both breast and endometrial cancers, overexpression of estrogen-induced genes is
      associated with better prognosis. We hypothesized that analysis of a panel of
      estrogen-induced genes can predict the outcome in ovarian carcinoma and
      potentially differentiate between tumors of varying hormonal responsiveness. From
      a cohort of 219 women undergoing ovarian cancer surgery from 2004 to 2007, 83
      patients were selected for inclusion. All patients had advanced stage
      ovarian/primary peritoneal high-grade serous carcinoma and underwent primary
      surgical debulking, followed by adjuvant treatment with platinum and taxane
      agents. The expression of ERalpha and six genes known to be induced by estrogen
      in the female reproductive tract (namely EIG121, sFRP1, sFRP4, RALDH2, PR, and
      IGF-1) was measured using quantitative RT-PCR. Unsupervised cluster analyses were
      used to categorize patients as high or low gene expressors. Gene expression
      results were then compared with those for ER immunohistochemistry. Clusters were
      compared using chi(2) analyses, and Cox proportional hazards models were used to
      evaluate survival outcomes. The median follow-up time was 38.7 months (range: 1
      68). A cluster defined by EIG121 and ERalpha segregated tumors into distinct
      groups of high and low gene expressors. Shorter overall survival (OS) was
      associated with high gene expression (HR 2.84 (1.11-7.30), P=0.03), even after
      adjustment for other covariates. No difference in ER immunohistochemistry
      expression was noted between gene clusters. In contrast to other hormonally
      driven cancers, high expression of ERalpha and the estrogen-induced gene EIG121
      predicts shorter OS in patients with high-grade serous ovarian carcinoma. Such a
      biomarker panel may potentially be used to guide management with estrogen
      antagonists in this patient population.

PMID- 21102416
TI  - Methylation of the 3p22 region encompassing MLH1 is representative of the CpG
      island methylator phenotype in colorectal cancer.
AB  - Epigenetic silencing of cancer-related genes by promoter methylation is a
      frequent event in sporadic colorectal cancer. The CpG island methylator phenotype
      (CIMP+), in which discrete genes throughout the genome are simultaneously
      methylated, and long-range epigenetic silencing, whereby multiple genes within
      contiguous chromosomal regions are methylated, have been described in subsets of
      colorectal cancer. We previously reported the concurrent methylation of the
      mismatch repair gene MLH1 with a cluster of flanking genes in chromosome region
      3p22 in sporadic colorectal carcinoma exhibiting microsatellite instability and
      the BRAF V600E mutation. Herein, we aimed to determine whether methylation of
      MLH1 and neighbouring 3p22 genes, singly or concomitantly, correlate with the
      germline c.-93G>A SNP within the MLH1 promoter, CIMP+ and other
      clinicopathological and molecular features of the tumours. By studying a cohort
      of 946 sporadic colorectal cancer cases, we show a strong association between
      concordant methylation of >= 3 of five 3p22 genes with CIMP+ and the BRAF V600E
      mutation (P<0.001). These associations were independent of microsatellite
      instability, as concomitant methylation of 3p22 genes other than MLH1 was found
      in microsatellite stable cancers. These findings show that long-range epigenetic
      silencing across 3p22 occurs in the context of CIMP+ and the BRAF V600E mutation,
      and only gives rise to microsatellite instability when this process encompasses
      MLH1. Furthermore, the strong relationship between long-range epigenetic
      silencing of 3p22 and CIMP+ provides further evidence that these two purportedly
      distinct epigenetic phenotypes represent a single entity with a common aetiology.
      Low-level methylation of MLH1 and flanking 3p22 genes, as well as the BRAF V600E
      mutation, were detected in the apparently normal colonic mucosa of a small number
      of cases whose tumours showed a similar molecular profile, suggesting that these
      concurring genetic and epigenetic events can occur as a field defect in
      neoplastic development.

PMID- 21102417
TI  - Genomic instability and oncogene amplifications in colorectal adenomas predict
      recurrence and synchronous carcinoma.
AB  - Individual colorectal adenomas have different propensities to progress to
      invasive disease. In this study, we explored whether these differences could be
      explained by gene copy number alterations. We evaluated 18 adenomas of patients
      without synchronous or subsequent carcinoma (6.5 years follow-up), 23 adenomas of
      carcinoma patients, and 6 related carcinomas. All samples were measured for their
      DNA ploidy status. Centromere probes for chromosomes 17 and 18, as well as gene
      specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by
      multicolor fluorescence in situ hybridization. An increased genomic instability
      index of CEP17, SMAD7, and EGFR, as well as TP53 deletions and MYC amplifications
      defined adenomas of patients with synchronous carcinoma (P<0.05). Diploid NCOA3
      signal counts were associated with longer adenoma recurrence-free surveillance
      (P=0.042). In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as
      TP53 deletions correlated with increased DNA stem line values and/or aneuploidy
      in adenomas (P<0.05). Furthermore, aberrations of NCOA3, MYC, and RAB20 were
      associated with histopathologically defined high-risk adenomas (P<0.05). RAB20
      amplifications were also correlated with high-grade dysplastic adenomas
      (P=0.002). We conclude that genomic instability in colorectal adenomas is
      reflected by EGFR, MYC, NCOA3, and RAB20 amplifications that do correlate with
      histomorphological features and are indicative for adenoma recurrence and the
      presence of synchronous carcinomas.

PMID- 21102418
TI  - Specificity of brachyury in the distinction of chordoma from clear cell renal
      cell carcinoma and germ cell tumors: a study of 305 cases.
AB  - Brachyury is recognized as a specific marker for notochord-derived tissues and
      neoplasms, and has become a defining immunohistochemical feature of chordoma. The
      main differential diagnostic consideration for chordoma is chondrosarcoma, which
      is known to lack brachyury expression. However, within the spectrum of
      genitourinary neoplasia, metastatic germ cell tumors and clear cell renal cell
      carcinoma may also be close morphological mimics of chordoma, particularly given
      the increasing prevalence of small tissue samples from image-guided biopsies.
      Although immunoreactivity for brachyury has been reported in a few germ cell
      tumors, a thorough characterization of staining by specific subtype has not been
      performed in a large series. Additionally, brachyury expression in clear cell
      renal cell carcinoma has not been well studied. In this study,
      immunohistochemical expression with the brachyury antibody was evaluated in 111
      germ cell tumors, 30 non-neoplastic and neoplastic (non-germ cell) testicular
      tissues, and 184 metastatic clear cell renal cell carcinomas using tissue
      microarray technology. In addition, immunoreactivity for PAX-8 and SALL-4 was
      evaluated in 12 chordomas on whole section. No nuclear brachyury expression was
      identified in any of the 101 germ cell tumors within the tissue microarray
      (including choriocarcinoma (1), embryonal carcinoma (20), intratubular germ cell
      neoplasia unclassified (2), seminoma (64), spermatocytic seminoma (1), teratoma
      (5) and yolk sac tumor (8)), in any of the 30 non-neoplastic and neoplastic (non
      germ cell) testicular tissues, or in any of the 10 whole-section seminomas. All
      184 metastatic clear cell renal cell carcinomas were also non-reactive for
      brachyury. All 12 chordomas showed strong nuclear immunoreactivity for brachyury,
      but no expression of SALL-4. In all, 1 of 12 chordoma cases showed patchy, 1+
      nuclear immunoreactivity for PAX-8. This study confirms the specificity of
      brachyury for chordoma in the differential diagnostic distinction from the
      potential genitourinary mimics, germ cell tumors and metastatic clear cell renal
      cell carcinoma.

PMID- 21102419
TI  - Loss of SerpinA5 protein expression is associated with advanced-stage serous
      ovarian tumors.
AB  - Epithelial ovarian cancer, the most lethal neoplasm of the female genital tract,
      is usually diagnosed at an advanced stage as obvious symptoms are absent at early
      stages. This disease is believed to originate from malignant transformation of
      the ovarian surface epithelium or fallopian tube. Histologically, several
      subtypes are being recognized, with serous histology accounting for the majority
      of cases. Serous tumors include serous borderline tumors and serous carcinomas. A
      better understanding of the tumor biology and molecular mechanisms involved in
      these tumors is needed, as both patient management and prognosis differ
      substantially. Previous microarray analysis identified SerpinA5, a uPA inhibitor,
      as key regulator for indolent borderline behavior. As carcinomas are
      characterized by loss of SerpinA5 mRNA expression, we hypothesized that SerpinA5
      protein expression is reduced or lost in carcinomas when compared with borderline
      tumors. We performed SerpinA5 immunohistochemical staining on 32 serous
      borderline tumors, 187 primary serous carcinomas and 62 serous omental
      metastases. Reduced or absent SerpinA5 protein staining was observed in
      carcinomas when compared with borderline tumors (P<0.001). SerpinA5 protein
      expression was significantly lowered in the omental metastases (P<0.001) when
      compared with the matching primary carcinoma. Interestingly, SerpinA5 protein
      expression was reduced in advanced-stage borderline tumors, often characterized
      by micropapillary growth and/or microinvasion, when compared with early-stage
      borderline tumors (P=0.015). In conclusion, SerpinA5 expression is significantly
      reduced in advanced-stage serous borderline tumors and serous carcinomas when
      compared with the early-stage counterparts, and reduction of expression is linked
      to more aggressive features of borderline tumors.

PMID- 21102420
TI  - Semiquantitative hormone receptor level influences response to trastuzumab
      containing neoadjuvant chemotherapy in HER2-positive breast cancer.
AB  - Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in
      hormone receptor-negative/HER2+ tumors is seen in 27-45% of cases. In contrast,
      estrogen receptor (ER)+/HER2+ tumors demonstrate pathologic complete response in
      ~ 8% of cases and is generally limited to weak-to-moderate ER+/HER2+ tumors. It
      is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen
      will increase the pathologic complete response rates in all HER2+ tumors. A list
      of HER2+ patients who received neoadjuvant chemotherapy (with trastuzumab) in the
      years 2007-2010 was obtained from our hospital database. The 104 HER2+ tumors
      were classified into three groups based on semiquantitative hormone receptor and
      HER2 results as follows: ERBB2 (ER-/PR-[H-score <=10]/HER2+), Luminal B-HER2
      Hybrid (LBHH; weak to moderate ER+ [H-score 11-199]/HER2+), and Luminal A-HER2
      Hybrid (LAHH; strong ER+[H-score >=200]/HER2+). Pathologic complete response was
      defined as absence of invasive carcinoma in the resection specimen and in the
      lymph nodes. Percentage tumor volume reduction was also calculated based on
      pretherapy size and detailed evaluation of the resection specimen. In all, 52%
      (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was
      significantly higher than the pathologic complete response rate in LBHH (33%; 10
      of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction
      was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%)
      tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy
      regimen significantly increases the pathologic complete response rates in all
      HER2+ tumors. However, the benefit of trastuzumab is highest in ER-negative
      tumors and progressively decreases with increase in tumor ER expression. This
      information can be utilized to counsel patients considered for neoadjuvant
      chemotherapy and the same principle could be applied in the adjuvant setting.

PMID- 21102421
TI  - Marginal zone lymphomas involving meningeal dura: possible link to IgG4-related
      diseases.
AB  - Dura-based marginal zone lymphomas represent an uncommon group of low-grade B
      cell neoplasms, and literature regarding the clinical, histological and genetic
      profile of these tumors in the context of the newly described IgG4-related
      entities is lacking. We analyzed 32 dura-based marginal zone lymphomas identified
      in 27 females and 5 males ranging in age from 33-82 years (median 50).
      Morphologic examination, immunohistochemical studies and PCR for B-cell clonality
      were carried out in all cases. In addition, IgG4 immunohistochemistry and
      cytogenetic studies (either by FISH or RT-PCR) were carried out in 20 (18 primary
      dural; 2 with associated extradural disease) and 9 cases, respectively.
      Clinically, most cases presented radiologically as dura-based masses, mimicking
      meningioma. Histologically, the majority exhibited plasmacytoid differentiation,
      and were clonal either by PCR or immunohistochemical light chain analysis (28 out
      of 32). In the subset tested for IgG4, 6 of 18 primary dural marginal zone
      lymphoma (including one epidural tumor) showed numerous IgG4-positive plasma
      cells; all 6 were light chain restricted and clonal by PCR in 5 of 6 tested
      cases. Three IgG4-positive marginal zone lymphomas tested for cytogenetics did
      not show any cytogenetic aberrations. Across all cases, FISH and RT-PCR
      identified abnormalities in three out of nine cases (trisomies 3 and 18;
      trisomies 3 and 1; trisomy 18) without any extranodal marginal zone lymphoma
      specific translocations. Regardless of the treatment modality, 16 of 17 patients
      with follow-up are alive without evidence of disease over a period of 4-124
      months (median 19.5). The expression of IgG4 in light-chain-restricted clonal
      plasma cells of a significant subset of dural marginal zone lymphomas, including
      one in an epidural location, is a novel finding and points to distinctive
      biology. Cytogenetic aberrations are present only in a minority of dural marginal
      zone lymphomas.

PMID- 21102422
TI  - A phase I dose-escalation clinical trial of intraoperative direct intratumoral
      injection of HF10 oncolytic virus in non-resectable patients with advanced
      pancreatic cancer.
AB  - In 2005, we initiated a clinical trial that examined the efficacy of the
      oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to
      have a high mortality rate, despite multimodal treatments for patients, and new
      therapeutic methods are greatly needed. The current mainstream methods for cancer
      treatment include biological therapeutics such as trastuzumab (Herceptin) for
      breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic
      virus therapy is a new and promising treatment strategy for cancer. Oncolytic
      viruses are novel biological therapeutics for advanced cancer that appear to have
      a wide spectrum of anticancer activity with minimal human toxicity. To examine
      the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot
      studies by injecting six patients with non-resectable pancreatic cancer with
      three doses of HF10. All patients were monitored for 30 days for local and
      systemic adverse effects and were not administered any other therapeutics during
      this period. There were no adverse side-effects, and we observed some therapeutic
      potential based on tumor marker levels, survival, pathological findings and
      diagnostic radiography. The tumors were classified as stable disease in three
      patients, partial response in one patient and progressive disease in two
      patients.

PMID- 21102423
TI  - Novel adenovirus-based helper system to support production of recombinant
      parvovirus.
AB  - Preclinical studies using various cell culture and animal systems highlight the
      potential of recombinant rodent parvoviruses (recPVs) for cancer therapy.
      Production of these viruses is, however, not efficient and this hampers the
      clinical applications of these agents. In this study, we show that the adenovirus
      genes E2a, E4(orf6) and VA RNA increase the production of recPVs by more than 10
      fold and reduce the time of production from 3 to 2 days in HEK293T cells. The
      helper effects of these genes can be observed with different recPVs, regardless
      of the nature and size of the inserted transgene. Furthermore, we generated a
      recombinant Adenovirus 5 carrying the parvovirus VP transcription unit. This
      helper, named Ad-VP, allows recPVs to be efficiently produced through a protocol
      based only on cell infection, making possible to use cell lines, such as NB324K,
      which are good producers of parvoviruses but are hardly transfectable. Hence, we
      could further improve viral titers and reduce time and costs of production. This
      Ad-VP helper-based protocol could be scaled up to a bioreactor format for the
      generation of the large amounts of recPVs needed for future clinical
      applications.

PMID- 21102424
TI  - Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs.
AB  - RNA interference (RNAi)-based gene silencing is widely used in laboratories for
      gene function studies and also holds a great promise for developing treatments
      for diseases. However, in vivo delivery of RNAi therapy remains a key issue.
      Lentiviral vectors have been employed for stable gene transfer and gene therapy
      and therefore are expected to deliver a stable and durable RNAi therapy. But this
      does not seem to be true in some disease models. Here, we showed that lentivirus
      delivered short-hairpin RNA (shRNA) against human papillomavirus (HPV) E6/E7
      oncogenes were effective for only 2 weeks in a cervical cancer model. However,
      using this vector to carry two copies of the same shRNA or two shRNAs targeting
      at two different but closely related genes (HPV E6 and vascular endothelial
      growth factor) was more effective at silencing the gene targets and inhibiting
      cell or even tumor growth than their single shRNA counterparts. The cancer cells
      treated with dual shRNA were also more sensitive to chemotherapeutic drugs than
      single shRNA-treated cells. These results suggest that a multi-shRNA strategy may
      be a more attractive approach for developing an RNAi therapy for this cancer.

PMID- 21102425
TI  - Seeking the causes and solutions to imatinib-resistance in chronic myeloid
      leukemia.
AB  - Although only 5000 new cases of chronic myeloid leukemia (CML) were seen in the
      United States in 2009, this neoplasm continues to make scientific headlines year
      after-year. Advances in understanding the molecular pathogenesis coupled with
      exciting developments in both drug design and development, targeting the
      initiating tyrosine kinase, have kept CML in the scientific limelight for more
      than a decade. Indeed, imatinib, a small-molecule inhibitor of the leukemia
      initiating Bcr-Abl tyrosine kinase, has quickly become the therapeutic standard
      for newly diagnosed chronic phase-CML (CP-CML) patients. Yet, nearly one-third of
      patients will still have an inferior response to imatinib, either failing to
      respond to primary therapy or demonstrating progression after an initial
      response. Significant efforts geared toward understanding the molecular
      mechanisms of imatinib resistance have yielded valuable insights into the
      cellular biology of drug trafficking, enzyme structure and function, and the
      rational design of novel small molecule enzyme inhibitors. Indeed, new classes of
      kinase inhibitors have recently been investigated in imatinib-resistant CML.
      Understanding the pathogenesis of tyrosine kinase inhibitor resistance and the
      molecular rationale for the development of second and now third generation
      therapies for patients with CML will be keys to further disease control over the
      next 10 years.

PMID- 21102426
TI  - Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of
      PinX1.
AB  - Increased expression of BAFF (B cell-activating factor belonging to the TNF
      family) and its receptors has been identified in numerous B-cell malignancies. A
      soluble human BAFF mutant (mBAFF), binding to BAFF receptors but failing to
      activate B-lymphocyte proliferation, may function as a competitive inhibitor of
      BAFF and may serve as a novel ligand for targeted therapy of BAFF receptor
      positive malignancies. Pin2/TRF1-interacting protein X1 (PinX1), a nucleolar
      protein, potently inhibits telomerase activity and affects tumorigenicity. In
      this study, we generated novel recombinant proteins containing mBAFF, a
      polyarginine tract 9R and PinX1 (or its C/N terminal), to target lymphoma cells.
      The fusion proteins PinX1/C-G(4)S-9R-G(4)S-mBAFF and PinX1/C-9R-mBAFF
      specifically bind and internalize into BAFF receptor-positive cells, and
      subsequently induce growth inhibition and apoptosis. The selective cytotoxicity
      of the fusion proteins is a BAFF receptor-mediated process and depends on mBAFF,
      PinX1/C and 9R. Moreover, the fusion proteins specifically kill BAFF receptor
      expressing Burkitt's lymphoma (BL) cells by inhibiting telomerase activity and
      the consequent shortening of telomeres. Therapeutic experiments using PinX1C
      G(4)S-9R-G(4)S-mBAFF in severe combined immunodeficient (SCID) mice implanted
      with Raji cells showed significantly prolonged survival times, indicating the in
      vivo antitumor activity of the fusion protein. These results suggest the
      potential of PinX1/C-G(4)S-9R-G(4)S-mBAFF in targeted therapy of BL.

PMID- 21102427
TI  - HDAC inhibition by LBH589 affects the phenotype and function of human myeloid
      dendritic cells.
AB  - LBH589 is a novel pan-histone deacetylase (HDAC) inhibitor that has potent
      antitumor activity in multiple myeloma and other hematological malignancies.
      However, its impact on the immune system has not been defined. We here evaluated
      the effects of LBH589 on human myeloid dendritic cells (DCs) at clinically
      relevant concentrations. Exposure to LBH589 affected the surface molecule
      expression on immature and mature DCs, which was associated with DC maturation
      (CD83?), antigen presentation (human leukocyte antigen-ABC?) and T-cell co
      stimulation (CD40? and CD86?). LBH589 decreased both protein and polysaccharide
      antigen uptake capacities by DCs. Importantly, LBH589 impaired DC function to
      stimulate antigen-specific immune responses, resulting in the significant
      reduction of invariant natural killer T-cell (CD1d-restricted) and T-cell (major
      histocompatibility complex-restricted) activation in innate and adaptive
      immunity. LBH589 also significantly repressed the production of interleukin (IL)
      6, IL-10, IL-12p70, IL-23 and tumor necrosis factor-alpha by Toll-like receptor
      (TLR)3 and TLR4-induced DC activation, indicating an important role of HDAC
      activity in immune regulation and inflammation. RelB, a component of the nuclear
      factor-kappa B signaling pathway, was the key component regulated by HDAC
      inhibition in DCs. Together, our preclinical study demonstrates that LBH589
      significantly impairs the phenotype and function of DCs, indicating a need for
      monitoring the immune status in patients receiving HDAC inhibitor therapy. It
      also provides a rationale to evaluate LBH589 activity for the treatment of
      inflammation.

PMID- 21102428
TI  - Integrated use of minimal residual disease classification and IKZF1 alteration
      status accurately predicts 79% of relapses in pediatric acute lymphoblastic
      leukemia.
AB  - Response to therapy as determined by minimal residual disease (MRD) is currently
      used for stratification in treatment protocols for pediatric acute lymphoblastic
      leukemia (ALL). However, the large MRD-based medium risk group (MRD-M; 50-60% of
      the patients) harbors many relapses. We analyzed MRD in 131 uniformly treated
      precursor-B-ALL patients and evaluated whether combined MRD and IKZF1 (Ikaros
      zinc finger-1) alteration status can improve risk stratification. We confirmed
      the strong prognostic significance of MRD classification, which was independent
      of IKZF1 alterations. Notably, 8 of the 11 relapsed cases in the large MRD-M
      group (n=81; 62%) harbored an IKZF1 alteration. Integration of both MRD and IKZF1
      status resulted in a favorable outcome group (n=104; 5 relapses) and a poor
      outcome group (n=27; 19 relapses), and showed a stronger prognostic value than
      each of the established risk factors alone (hazard ratio (95%CI): 24.98 (8.29
      75.31)). Importantly, whereas MRD and IKZF1 status alone identified only 46 and
      54% of the relapses, respectively, their integrated use allowed prediction of 79%
      of all the relapses with 93% specificity. Because of the unprecedented
      sensitivity in upfront relapse prediction, the combined parameters have high
      potential for future risk stratification, particularly for patients originally
      classified as non-high risk, such as the large group of MRD-M patients.

PMID- 21102429
TI  - ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the
      cellular regulator RIN1.
AB  - ABL gene translocations create constitutively active tyrosine kinases that are
      causative in chronic myeloid leukemia, acute lymphocytic leukemia and other
      hematopoietic malignancies. Consistent retention of ABL SH3/SH2 autoinhibitory
      domains, however, suggests that these leukemogenic tyrosine kinase fusion
      proteins remain subject to regulation. We resolve this paradox, demonstrating
      that BCR-ABL1 kinase activity is regulated by RIN1, an ABL SH3/SH2 binding
      protein. BCR-ABL1 activity was increased by RIN1 overexpression and decreased by
      RIN1 silencing. Moreover, Rin1(-/-) bone marrow cells were not transformed by BCR
      ABL1, ETV6-ABL1 or BCR-ABL1(T315I), a patient-derived drug-resistant mutant, as
      judged by growth factor independence. Rescue by ectopic RIN1 verified a cell
      autonomous mechanism of collaboration with BCR-ABL1 during transformation.
      Sensitivity to the ABL kinase inhibitor imatinib was increased by RIN1 silencing,
      consistent with RIN1 stabilization of an activated BCR-ABL1 conformation having
      reduced drug affinity. The dependence on activation by RIN1 to unleash full
      catalytic and cell transformation potential reveals a previously unknown
      vulnerability that could be exploited for treatment of leukemic cases driven by
      ABL translocations. The findings suggest that RIN1 targeting could be efficacious
      for imatinib-resistant disease and might complement ABL kinase inhibitors in
      first-line therapy.

PMID- 21102431
TI  - The IMAGEN study: reinforcement-related behaviour in normal brain function and
      psychopathology.
AB  - A fundamental function of the brain is to evaluate the emotional and motivational
      significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is
      the first multicentre genetic-neuroimaging study aimed at identifying the genetic
      and neurobiological basis of individual variability in impulsivity, reinforcer
      sensitivity and emotional reactivity, and determining their predictive value for
      the development of frequent psychiatric disorders. Comprehensive behavioural and
      neuropsychological characterization, functional and structural neuroimaging and
      genome-wide association analyses of 2000 14-year-old adolescents are combined
      with functional genetics in animal and human models. Results will be validated in
      1000 adolescents from the Canadian Saguenay Youth Study. The sample will be
      followed up longitudinally at the age of 16 years to investigate the predictive
      value of genetics and intermediate phenotypes for the development of frequent
      psychiatric disorders. This review describes the strategies the IMAGEN consortium
      used to meet the challenges posed by large-scale multicentre imaging-genomics
      investigations. We provide detailed methods and Standard Operating Procedures
      that we hope will be helpful for the design of future studies. These include
      standardization of the clinical, psychometric and neuroimaging-acquisition
      protocols, development of a central database for efficient analyses of large
      multimodal data sets and new analytic approaches to large-scale genetic
      neuroimaging analyses.

PMID- 21102433
TI  - Glioblastoma stem-like cells give rise to tumour endothelium.
AB  - Glioblastoma (GBM) is among the most aggressive of human cancers. A key feature
      of GBMs is the extensive network of abnormal vasculature characterized by
      glomeruloid structures and endothelial hyperplasia. Yet the mechanisms of
      angiogenesis and the origin of tumour endothelial cells remain poorly defined.
      Here we demonstrate that a subpopulation of endothelial cells within
      glioblastomas harbour the same somatic mutations identified within tumour cells,
      such as amplification of EGFR and chromosome 7. We additionally demonstrate that
      the stem-cell-like CD133(+) fraction includes a subset of vascular endothelial
      cadherin (CD144)-expressing cells that show characteristics of endothelial
      progenitors capable of maturation into endothelial cells. Extensive in vitro and
      in vivo lineage analyses, including single cell clonal studies, further show that
      a subpopulation of the CD133(+) stem-like cell fraction is multipotent and
      capable of differentiation along tumour and endothelial lineages, possibly via an
      intermediate CD133(+)/CD144(+) progenitor cell. The findings are supported by
      genetic studies of specific exons selected from The Cancer Genome Atlas,
      quantitative FISH and comparative genomic hybridization data that demonstrate
      identical genomic profiles in the CD133(+) tumour cells, their endothelial
      progenitor derivatives and mature endothelium. Exposure to the clinical anti
      angiogenesis agent bevacizumab or to a gamma-secretase inhibitor as well as
      knockdown shRNA studies demonstrate that blocking VEGF or silencing VEGFR2
      inhibits the maturation of tumour endothelial progenitors into endothelium but
      not the differentiation of CD133(+) cells into endothelial progenitors, whereas
      gamma-secretase inhibition or NOTCH1 silencing blocks the transition into
      endothelial progenitors. These data may provide new perspectives on the
      mechanisms of failure of anti-angiogenesis inhibitors currently in use. The
      lineage plasticity and capacity to generate tumour vasculature of the putative
      cancer stem cells within glioblastoma are novel findings that provide new insight
      into the biology of gliomas and the definition of cancer stemness, as well as the
      mechanisms of tumour neo-angiogenesis.

PMID- 21102434
TI  - Tumour vascularization via endothelial differentiation of glioblastoma stem-like
      cells.
AB  - Glioblastoma is a highly angiogenetic malignancy, the neoformed vessels of which
      are thought to arise by sprouting of pre-existing brain capillaries. The recent
      demonstration that a population of glioblastoma stem-like cells (GSCs) maintains
      glioblastomas indicates that the progeny of these cells may not be confined to
      the neural lineage. Normal neural stem cells are able to differentiate into
      functional endothelial cells. The connection between neural stem cells and the
      endothelial compartment seems to be critical in glioblastoma, where cancer stem
      cells closely interact with the vascular niche and promote angiogenesis through
      the release of vascular endothelial growth factor (VEGF) and stromal-derived
      factor 1 (refs 5-9). Here we show that a variable number (range 20-90%, mean
      60.7%) of endothelial cells in glioblastoma carry the same genomic alteration as
      tumour cells, indicating that a significant portion of the vascular endothelium
      has a neoplastic origin. The vascular endothelium contained a subset of
      tumorigenic cells that produced highly vascularized anaplastic tumours with areas
      of vasculogenic mimicry in immunocompromised mice. In vitro culture of GSCs in
      endothelial conditions generated progeny with phenotypic and functional features
      of endothelial cells. Likewise, orthotopic or subcutaneous injection of GSCs in
      immunocompromised mice produced tumour xenografts, the vessels of which were
      primarily composed of human endothelial cells. Selective targeting of endothelial
      cells generated by GSCs in mouse xenografts resulted in tumour reduction and
      degeneration, indicating the functional relevance of the GSC-derived endothelial
      vessels. These findings describe a new mechanism for tumour vasculogenesis and
      may explain the presence of cancer-derived endothelial-like cells in several
      malignancies.

PMID- 21102436
TI  - Dynein at odd angles?
AB  - Cytoplasmic dynein drives vesicular transport from the periphery to the cell body
      of neurons. Missense mutations in the dynein tail domain cause neurodegenerative
      disease in mouse models. new data on the effect of one such dynein mutation
      provide insight into the intramolecular communication and flexible stepping of
      this essential cellular motor.

PMID- 21102435
TI  - ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I
      during antiviral responses.
AB  - The poly(ADP-ribose) polymerases (PARPs) participate in many biological and
      pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS),
      rather than the full-length protein (ZAP), was selectively induced by 5'
      triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of
      interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS
      associated with RIG-I to promote the oligomerization and ATPase activity of RIG
      I, which led to robust activation of IRF3 and NF-kappaB transcription factors.
      Disruption of the gene encoding ZAPS resulted in impaired induction of interferon
      alpha (IFN-alpha), IFN-beta and other cytokines after viral infection. These
      results indicate that ZAPS is a key regulator of RIG-I signaling during the
      innate antiviral immune response, which suggests its possible use as a
      therapeutic target for viral control.

PMID- 21102437
TI  - Human IRGM regulates autophagy and cell-autonomous immunity functions through
      mitochondria.
AB  - IRGM, a human immunity-related GTPase, confers autophagic defence against
      intracellular pathogens by an unknown mechanism. Here, we report an unexpected
      mode of IRGM action. IRGM demonstrated differential affinity for the
      mitochondrial lipid cardiolipin, translocated to mitochondria, affected
      mitochondrial fission and induced autophagy. Mitochondrial fission was necessary
      for autophagic control of intracellular mycobacteria by IRGM. IRGM influenced
      mitochondrial membrane polarization and cell death. Overexpression of IRGMd, but
      not IRGMb splice isoforms, caused mitochondrial depolarization and autophagy
      independent, but Bax/Bak-dependent, cell death. By acting on mitochondria, IRGM
      confers autophagic protection or cell death, explaining IRGM action both in
      defence against tuberculosis and in the damaging inflammation caused by Crohn's
      disease.

PMID- 21102438
TI  - AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade.
AB  - Mitogen-activated protein kinase (MAPK) cascades propagate a variety of cellular
      activities. Processive relay of signals through RAF-MEK-ERK modulates cell growth
      and proliferation. Signalling through this ERK cascade is frequently amplified in
      cancers, and drugs such as sorafenib (which is prescribed to treat renal and
      hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases.
      Natural factors that influence ERK1/2 signalling include the second messenger
      cyclic AMP. However, the mechanisms underlying this cascade have been difficult
      to elucidate. We demonstrate that the A-kinase-anchoring protein AKAP-Lbc and the
      scaffolding protein kinase suppressor of Ras (KSR-1) form the core of a
      signalling network that efficiently relay signals from RAF, through MEK, and on
      to ERK1/2. AKAP-Lbc functions as an enhancer of ERK signalling by securing RAF in
      the vicinity of MEK1 and synchronizing protein kinase A (PKA)-mediated
      phosphorylation of Ser 838 on KSR-1. This offers mechanistic insight into cAMP
      responsive control of ERK signalling events.

PMID- 21102439
TI  - A cytoplasmic dynein tail mutation impairs motor processivity.
AB  - Mutations in the tail of the cytoplasmic dynein molecule have been reported to
      cause neurodegenerative disease in mice. The mutant mouse strain Legs at odd
      angles (Loa) has impaired retrograde axonal transport, but the molecular
      deficiencies in the mutant dynein molecule, and how they contribute to
      neurodegeneration, are unknown. To address these questions, we purified dynein
      from wild-type mice and the Legs at odd angles mutant mice. Using biochemical,
      single-molecule, and live-cell-imaging techniques, we find a marked inhibition of
      motor run-length in vitro and in vivo, and significantly altered motor domain
      coordination in the dynein from mutant mice. These results suggest a potential
      role for the dynein tail in motor function, and provide direct evidence for a
      link between single-motor processivity and disease.

PMID- 21102440
TI  - MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop
      promoting calcineurin/NFAT signalling.
AB  - MicroRNAs (miRs) are a class of single-stranded, non-coding RNAs of about 22
      nucleotides in length. Increasing evidence implicates miRs in myocardial disease
      processes. Here we show that miR-199b is a direct calcineurin/NFAT target gene
      that increases in expression in mouse and human heart failure, and targets the
      nuclear NFAT kinase dual-specificity tyrosine-(Y)-phosphorylation regulated
      kinase 1a (Dyrk1a), constituting a pathogenic feed forward mechanism that affects
      calcineurin-responsive gene expression. Mutant mice overexpressing miR-199b, or
      haploinsufficient for Dyrk1a, are sensitized to calcineurin/NFAT signalling or
      pressure overload and show stress-induced cardiomegaly through reduced Dyrk1a
      expression. In vivo inhibition of miR-199b by a specific antagomir normalized
      Dyrk1a expression, reduced nuclear NFAT activity and caused marked inhibition and
      even reversal of hypertrophy and fibrosis in mouse models of heart failure. Our
      results reveal that microRNAs affect cardiac cellular signalling and gene
      expression, and implicate miR-199b as a therapeutic target in heart failure.

PMID- 21102441
TI  - Tissue elongation requires oscillating contractions of a basal actomyosin
      network.
AB  - Understanding how molecular dynamics leads to cellular behaviours that ultimately
      sculpt organs and tissues is a major challenge not only in basic developmental
      biology but also in tissue engineering and regenerative medicine. Here we use
      live imaging to show that the basal surfaces of Drosophila follicle cells undergo
      a series of directional, oscillating contractions driven by periodic myosin
      accumulation on a polarized actin network. Inhibition of the actomyosin
      contractions or their coupling to extracellular matrix (ECM) blocked elongation
      of the whole tissue, whereas enhancement of the contractions exaggerated it.
      Myosin accumulated in a periodic manner before each contraction and was regulated
      by the small GTPase Rho, its downstream kinase, ROCK, and cytosolic calcium.
      Disrupting the link between the actin cytoskeleton and the ECM decreased the
      amplitude and period of the contractions, whereas enhancing cell-ECM adhesion
      increased them. In contrast, disrupting cell-cell adhesions resulted in loss of
      the actin network. Our findings reveal a mechanism controlling organ shape and an
      experimental model for the study of the effects of oscillatory actomyosin
      activity within a coherent cell sheet.

PMID- 21102442
TI  - A small GTPase molecular switch regulates epigenetic centromere maintenance by
      stabilizing newly incorporated CENP-A.
AB  - Epigenetic mechanisms regulate genome activation in diverse events, including
      normal development and cancerous transformation. Centromeres are epigenetically
      designated chromosomal regions that maintain genomic stability by directing
      chromosome segregation during cell division. The histone H3 variant CENP-A
      resides specifically at centromeres, is fundamental to centromere function and is
      thought to act as the epigenetic mark defining centromere loci. Mechanisms
      directing assembly of CENP-A nucleosomes have recently emerged, but how CENP-A is
      maintained after assembly is unknown. Here, we show that a small GTPase switch
      functions to maintain newly assembled CENP-A nucleosomes. Using functional
      proteomics, we found that MgcRacGAP (a Rho family GTPase activating protein)
      interacts with the CENP-A licensing factor HsKNL2. High-resolution live-cell
      imaging assays, designed in this study, demonstrated that MgcRacGAP, the Rho
      family guanine nucleotide exchange factor (GEF) Ect2, and the small GTPases Cdc42
      and Rac, are required for stability of newly incorporated CENP-A at centromeres.
      Thus, a small GTPase switch ensures epigenetic centromere maintenance after
      loading of new CENP-A.

PMID- 21102443
TI  - Transcriptional regulation of BRCA1 expression by a metabolic switch.
AB  - Though the linkages between germline mutations of BRCA1 and hereditary breast
      cancer are well known, recent evidence suggests that altered BRCA1 transcription
      may also contribute to sporadic forms of breast cancer. Here we show that BRCA1
      expression is controlled by a dynamic equilibrium between transcriptional
      coactivators and co-repressors that govern histone acetylation and DNA
      accessibility at the BRCA1 promoter. Eviction of the transcriptional co-repressor
      and metabolic sensor, C terminal-binding protein (CtBP), has a central role in
      this regulation. Loss of CtBP from the BRCA1 promoter through estrogen induction,
      depletion by RNA interference or increased NAD+/NADH ratio leads to HDAC1
      dismissal, elevated histone acetylation and increased BRCA1 transcription. The
      active control of chromatin marks, DNA accessibility and gene expression at the
      BRCA1 promoter by this 'metabolic switch' provides an important molecular link
      between caloric intake and tumor suppressor expression in mammary cells.

PMID- 21102444
TI  - Dissection of Dom34-Hbs1 reveals independent functions in two RNA quality control
      pathways.
AB  - Eukaryotic cells have several quality control pathways that rely on translation
      to detect and degrade defective RNAs. Dom34 and Hbs1 are two proteins that are
      related to translation termination factors and are involved in no-go decay (NGD)
      and nonfunctional 18S ribosomal RNA (rRNA) decay (18S NRD) pathways that
      eliminate RNAs that cause strong ribosomal stalls. Here we present the structure
      of Hbs1 with and without GDP and a low-resolution model of the Dom34-Hbs1
      complex. This complex mimics complexes of the elongation factor and transfer RNA
      or of the translation termination factors eRF1 and eRF3, supporting the idea that
      it binds to the ribosomal A-site. We show that nucleotide binding by Hbs1 is
      essential for NGD and 18S NRD. Mutations in Hbs1 that disrupted the interaction
      between Dom34 and Hbs1 strongly impaired NGD but had almost no effect on 18S NRD.
      Hence, NGD and 18S NRD could be genetically uncoupled, suggesting that mRNA and
      rRNA in a stalled translation complex may not always be degraded simultaneously.

PMID- 21102445
TI  - Mre11-Rad50-Xrs2 and Sae2 promote 5' strand resection of DNA double-strand
      breaks.
AB  - The repair of DNA double-strand breaks (DSBs) by homologous recombination is
      essential for genomic stability. The first step in this process is resection of
      5' strands to generate 3' single-stranded DNA intermediates. Efficient resection
      in budding yeast requires the Mre11-Rad50-Xrs2 (MRX) complex and the Sae2
      protein, although the role of MRX has been unclear because Mre11 paradoxically
      has 3'->5' exonuclease activity in vitro. Here we reconstitute resection with
      purified MRX, Sae2 and Exo1 proteins and show that degradation of the 5' strand
      is catalyzed by Exo1 yet completely dependent on MRX and Sae2 when Exo1 levels
      are limiting. This stimulation is mainly caused by cooperative binding of DNA
      substrates by Exo1, MRX and Sae2. This work establishes the direct role of MRX
      and Sae2 in promoting the resection of 5' strands in DNA DSB repair.

PMID- 21102446
TI  - Initiation complex dynamics direct the transitions between distinct phases of
      early HIV reverse transcription.
AB  - Human immunodeficiency virus (HIV) initiates reverse transcription of its viral
      RNA (vRNA) genome from a cellular tRNA(3)(Lys) primer. This process is
      characterized by a slow initiation phase with specific pauses, followed by a fast
      elongation phase. We report a single-molecule study that monitors the dynamics of
      individual initiation complexes, comprised of vRNA, tRNA and HIV reverse
      transcriptase (RT). RT transitions between two opposite binding orientations on
      tRNA-vRNA complexes, and the prominent pausing events are related to RT binding
      in a flipped orientation opposite to the polymerization-competent configuration.
      A stem-loop structure within the vRNA is responsible for maintaining the enzyme
      predominantly in this flipped orientation. Disruption of the stem-loop structure
      triggers the initiation-to-elongation transition. These results highlight the
      important role of the structural dynamics of the initiation complex in directing
      transitions between early reverse transcription phases.

PMID- 21102448
TI  - A common origin of synaptic vesicles undergoing evoked and spontaneous fusion.
AB  - There is a longstanding controversy on the identity of synaptic vesicles
      undergoing spontaneous versus evoked release. A recent study, introducing a new
      genetic probe, suggested that spontaneous release is driven by a resting pool of
      synaptic vesicles refractory to stimulation. We found that cross-depletion of
      spontaneously or actively recycling synaptic vesicle pools occurred on
      stimulation in rat hippocampal neurons and identified the recycling pool as a
      major source of spontaneous release.

PMID- 21102447
TI  - Thalamic synchrony and the adaptive gating of information flow to cortex.
AB  - Although it has long been posited that sensory adaptation serves to enhance
      information flow in sensory pathways, the neural basis remains elusive.
      Simultaneous single-unit recordings in the thalamus and cortex in anesthetized
      rats showed that adaptation differentially influenced thalamus and cortex in a
      manner that fundamentally changed the nature of information conveyed about
      vibrissa motion. Using an ideal observer of cortical activity, we found that
      performance in detecting vibrissal deflections degraded with adaptation while
      performance in discriminating among vibrissal deflections of different velocities
      was enhanced, a trend not observed in thalamus. Analysis of simultaneously
      recorded thalamic neurons did reveal, however, an analogous adaptive change in
      thalamic synchrony that mirrored the cortical response. An integrate-and-fire
      model using experimentally measured thalamic input reproduced the observed
      transformations. The results here suggest a shift in coding strategy with
      adaptation that directly controls information relayed to cortex, which could have
      implications for encoding velocity signatures of textures.

PMID- 21102449
TI  - Hippocampal brain-network coordination during volitional exploratory behavior
      enhances learning.
AB  - Exploratory behaviors during learning determine what is studied and when, helping
      to optimize subsequent memory performance. To elucidate the cognitive and neural
      determinants of exploratory behaviors, we manipulated the control that human
      subjects had over the position of a moving window through which they studied
      objects and their locations. Our behavioral, neuropsychological and neuroimaging
      data indicate that volitional control benefits memory performance and is linked
      to a brain network that is centered on the hippocampus. Increases in correlated
      activity between the hippocampus and other areas were associated with specific
      aspects of memory, which suggests that volitional control optimizes interactions
      among specialized neural systems through the hippocampus. Memory is therefore an
      active process that is intrinsically linked to behavior. Furthermore, brain
      structures that are typically seen as passive participants in memory encoding
      (for example, the hippocampus) are actually part of an active network that
      controls behavior dynamically as it unfolds.

PMID- 21102450
TI  - The same synaptic vesicles drive active and spontaneous release.
AB  - Synaptic vesicles release neurotransmitter both actively (on stimulation) and
      spontaneously (at rest). It has been assumed that identical vesicles use both
      modes of release; however, recent evidence has challenged this view. Using
      several assays (FM dye imaging, pHluorin imaging and antibody-labeling of
      synaptotagmin) in neuromuscular preparations from Drosophila, frog and mouse, as
      well as rat cultured neurons, we found that the same vesicles participate in
      active and spontaneous release.

PMID- 21102452
TI  - Limitations of next-generation genome sequence assembly.
AB  - High-throughput sequencing technologies promise to transform the fields of
      genetics and comparative biology by delivering tens of thousands of genomes in
      the near future. Although it is feasible to construct de novo genome assemblies
      in a few months, there has been relatively little attention to what is lost by
      sole application of short sequence reads. We compared the recent de novo
      assemblies using the short oligonucleotide analysis package (SOAP), generated
      from the genomes of a Han Chinese individual and a Yoruban individual, to
      experimentally validated genomic features. We found that de novo assemblies were
      16.2% shorter than the reference genome and that 420.2 megabase pairs of common
      repeats and 99.1% of validated duplicated sequences were missing from the genome.
      Consequently, over 2,377 coding exons were completely missing. We conclude that
      high-quality sequencing approaches must be considered in conjunction with high
      throughput sequencing for comparative genomics analyses and studies of genome
      evolution.

PMID- 21102451
TI  - Sortilin associates with Trk receptors to enhance anterograde transport and
      neurotrophin signaling.
AB  - Binding of target-derived neurotrophins to Trk receptors at nerve terminals is
      required to stimulate neuronal survival, differentiation, innervation and
      synaptic plasticity. The distance between the soma and nerve terminal is great,
      making efficient anterograde Trk transport critical for Trk synaptic
      translocation and signaling. The mechanism responsible for this trafficking
      remains poorly understood. Here we show that the sorting receptor sortilin
      interacts with TrkA, TrkB and TrkC and enables their anterograde axonal
      transport, thereby enhancing neurotrophin signaling. Cultured DRG neurons lacking
      sortilin showed blunted MAP kinase signaling and reduced neurite outgrowth upon
      stimulation with NGF. Moreover, deficiency for sortilin markedly aggravated TrkA,
      TrkB and TrkC phenotypes present in p75(NTR) knockouts, and resulted in increased
      embryonic lethality and sympathetic neuropathy in mice heterozygous for TrkA. Our
      findings demonstrate a role for sortilin as an anterograde trafficking receptor
      for Trk and a positive modulator of neurotrophin-induced neuronal survival.

PMID- 21102453
TI  - Protein localization in electron micrographs using fluorescence nanoscopy.
AB  - A complete portrait of a cell requires a detailed description of its molecular
      topography: proteins must be linked to particular organelles. Immunocytochemical
      electron microscopy can reveal locations of proteins with nanometer resolution
      but is limited by the quality of fixation, the paucity of antibodies and the
      inaccessibility of antigens. Here we describe correlative fluorescence electron
      microscopy for the nanoscopic localization of proteins in electron micrographs.
      We tagged proteins with the fluorescent proteins Citrine or tdEos and expressed
      them in Caenorhabditis elegans, fixed the worms and embedded them in plastic. We
      imaged the tagged proteins from ultrathin sections using stimulated emission
      depletion (STED) microscopy or photoactivated localization microscopy (PALM).
      Fluorescence correlated with organelles imaged in electron micrographs from the
      same sections. We used these methods to localize histones, a mitochondrial
      protein and a presynaptic dense projection protein in electron micrographs.

PMID- 21102454
TI  - Direct observation of local atomic order in a metallic glass.
AB  - The determination of the atomic configuration of metallic glasses is a long
      standing problem in materials science and solid-state physics. So far, only
      average structural information derived from diffraction and spectroscopic methods
      has been obtained. Although various atomic models have been proposed in the past
      fifty years, a direct observation of the local atomic structure in disordered
      materials has not been achieved. Here we report local atomic configurations of a
      metallic glass investigated by nanobeam electron diffraction combined with ab
      initio molecular dynamics simulation. Distinct diffraction patterns from
      individual atomic clusters and their assemblies, which have been theoretically
      predicted as short- and medium-range order, can be experimentally observed. This
      study provides compelling evidence of the local atomic order in the disordered
      material and has important implications in understanding the atomic mechanisms of
      metallic-glass formation and properties.

PMID- 21102455
TI  - A robust system for production of minicircle DNA vectors.
AB  - Minicircle DNA vectors allow sustained transgene expression in quiescent cells
      and tissues. To improve minicircle production, we genetically modified
      Escherichia coli to construct a producer strain that stably expresses a set of
      inducible minicircle-assembly enzymes, PhiC31 integrase and I-SceI homing
      endonuclease. This bacterial strain produces purified minicircles in a time frame
      and quantity similar to those of routine plasmid DNA preparation, making it
      feasible to use minicircles in place of plasmids in mammalian transgene
      expression studies.

PMID- 21102456
TI  - Large-scale in silico modeling of metabolic interactions between cell types in
      the human brain.
AB  - Metabolic interactions between multiple cell types are difficult to model using
      existing approaches. Here we present a workflow that integrates gene expression
      data, proteomics data and literature-based manual curation to model human
      metabolism within and between different types of cells. Transport reactions are
      used to account for the transfer of metabolites between models of different cell
      types via the interstitial fluid. We apply the method to create models of brain
      energy metabolism that recapitulate metabolic interactions between astrocytes and
      various neuron types relevant to Alzheimer's disease. Analysis of the models
      identifies genes and pathways that may explain observed experimental phenomena,
      including the differential effects of the disease on cell types and regions of
      the brain. Constraint-based modeling can thus contribute to the study and
      analysis of multicellular metabolic processes in the human tissue
      microenvironment and provide detailed mechanistic insight into high-throughput
      data analysis.

PMID- 21102457
TI  - STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in
      tumors.
AB  - Interleukin-6 (IL-6)-Janus kinase (JAK) signaling is viewed as crucial for
      persistent signal transducer and activator of transcription-3 (STAT3) activation
      in cancer. However, IL-6-induced STAT3 activation is normally transient. Here we
      identify a key mechanism for persistent STAT3 activation in tumor cells and the
      tumor microenvironment. We show that expression of sphingosine-1-phosphate
      receptor-1 (S1PR1), a G protein-coupled receptor for the lysophospholipid
      sphingosine-1-phosphate (S1P), is elevated in STAT3-positive tumors. STAT3 is a
      transcription factor for the S1pr1 gene. Reciprocally, enhanced S1pr1 expression
      activates STAT3 and upregulates Il6 gene expression, thereby accelerating tumor
      growth and metastasis in a STAT3-dependent manner. Silencing S1pr1 in tumor cells
      or immune cells inhibits tumor STAT3 activity, tumor growth and metastasis. S1P
      S1PR1-induced STAT3 activation is persistent, in contrast to transient STAT3
      activation by IL-6. S1PR1 activates STAT3 in part by upregulating JAK2 tyrosine
      kinase activity. We show that STAT3-induced S1PR1 expression, as well as the S1P
      S1PR1 pathway reciprocal regulation of STAT3 activity, is a major positive
      feedback loop for persistent STAT3 activation in cancer cells and the tumor
      microenvironment and for malignant progression.

PMID- 21102458
TI  - Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R.
AB  - Danger signals released upon cell damage can cause excessive immune-mediated
      tissue destruction such as that found in acute graft-versus-host disease (GVHD),
      allograft rejection and systemic inflammatory response syndrome. Given that ATP
      is found in small concentrations in the extracellular space under physiological
      conditions, and its receptor P2X(7)R is expressed on several immune cell types,
      ATP could function as a danger signal when released from dying cells. We observed
      increased ATP concentrations in the peritoneal fluid after total body
      irradiation, and during the development of GVHD in mice and in humans.
      Stimulation of antigen-presenting cells (APCs) with ATP led to increased
      expression of CD80 and CD86 in vitro and in vivo and actuated a cascade of
      proinflammatory events, including signal transducer and activator of
      transcription-1 (STAT1) phosphorylation, interferon-gamma (IFN-gamma) production
      and donor T cell expansion, whereas regulatory T cell numbers were reduced.
      P2X(7)R expression increased when GVHD evolved, rendering APCs more responsive to
      the detrimental effects of ATP, thereby providing positive feedback signals. ATP
      neutralization, early P2X(7)R blockade or genetic deficiency of P2X(7)R during
      GVHD development improved survival without immune paralysis. These data have
      major implications for transplantation medicine, as pharmacological interference
      with danger signals that act via P2X(7)R could lead to the development of
      tolerance without the need for intensive immunosuppression.

PMID- 21102459
TI  - Invasive three-dimensional organotypic neoplasia from multiple normal human
      epithelia.
AB  - Refined cancer models are required if researchers are to assess the burgeoning
      number of potential targets for cancer therapeutics in a clinically relevant
      context that allows a fast turnaround. Here we use tumor-associated genetic
      pathways to transform primary human epithelial cells from the epidermis,
      oropharynx, esophagus and cervix into genetically defined tumors in a human three
      dimensional (3D) tissue environment that incorporates cell-populated stroma and
      intact basement membrane. These engineered organotypic tissues recapitulated
      natural features of tumor progression, including epithelial invasion through
      basement membrane, a complex process that is necessary for biological malignancy
      in 90% of human cancers. Invasion was rapid and was potentiated by stromal cells.
      Oncogenic signals in 3D tissue, but not 2D culture, resembled gene expression
      profiles from spontaneous human cancers. We screened 3D organotypic neoplasia
      with well-characterized signaling pathway inhibitors to distill a clinically
      faithful cancer gene signature. Multitissue 3D human tissue cancer models may
      provide an efficient and relevant complement to current approaches to
      characterizing cancer progression.

PMID- 21102460
TI  - Conversion of vascular endothelial cells into multipotent stem-like cells.
AB  - Mesenchymal stem cells can give rise to several cell types, but varying results
      depending on isolation methods and tissue source have led to controversies about
      their usefulness in clinical medicine. Here we show that vascular endothelial
      cells can transform into multipotent stem-like cells by an activin-like kinase-2
      (ALK2) receptor-dependent mechanism. In lesions from individuals with
      fibrodysplasia ossificans progressiva (FOP), a disease in which heterotopic
      ossification occurs as a result of activating ALK2 mutations, or from transgenic
      mice expressing constitutively active ALK2, chondrocytes and osteoblasts
      expressed endothelial markers. Lineage tracing of heterotopic ossification in
      mice using a Tie2-Cre construct also suggested an endothelial origin of these
      cell types. Expression of constitutively active ALK2 in endothelial cells caused
      endothelial-to-mesenchymal transition and acquisition of a stem cell-like
      phenotype. Similar results were obtained by treatment of untransfected
      endothelial cells with the ligands transforming growth factor-beta2 (TGF-beta2)
      or bone morphogenetic protein-4 (BMP4) in an ALK2-dependent manner. These stem
      like cells could be triggered to differentiate into osteoblasts, chondrocytes or
      adipocytes. We suggest that conversion of endothelial cells to stem-like cells
      may provide a new approach to tissue engineering.

PMID- 21102461
TI  - Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS
      with PSD-95.
AB  - Stroke is a major public health problem leading to high rates of death and
      disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors
      (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are
      crucial for neuronal injury after stroke insult. However, directly inhibiting
      NMDARs or nNOS can cause severe side effects because they have key physiological
      functions in the CNS. Here we show that cerebral ischemia induces the interaction
      of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95
      interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS
      (nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic
      damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series of
      compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95
      interaction, ZL006. This drug blocked the ischemia-induced nNOS-PSD-95
      association selectively, had potent neuroprotective activity in vitro and
      ameliorated focal cerebral ischemic damage in mice and rats subjected to middle
      cerebral artery occlusion (MCAO) and reperfusion. Moreover, it readily crossed
      the blood-brain barrier, did not inhibit NMDAR function, catalytic activity of
      nNOS or spatial memory, and had no effect on aggressive behaviors. Thus, this new
      drug may serve as a treatment for stroke, perhaps without major side effects.

PMID- 21102464
TI  - RNA sequencing shows no dosage compensation of the active X-chromosome.
AB  - Mammalian cells from both sexes typically contain one active X chromosome but two
      sets of autosomes. It has previously been hypothesized that X-linked genes are
      expressed at twice the level of autosomal genes per active allele to balance the
      gene dose between the X chromosome and autosomes (termed 'Ohno's hypothesis').
      This hypothesis was supported by the observation that microarray-based gene
      expression levels were indistinguishable between one X chromosome and two
      autosomes (the X to two autosomes ratio (X:AA) ~1). Here we show that RNA
      sequencing (RNA-Seq) is more sensitive than microarray and that RNA-Seq data
      reveal an X:AA ratio of ~0.5 in human and mouse. In Caenorhabditis elegans
      hermaphrodites, the X:AA ratio reduces progressively from ~1 in larvae to ~0.5 in
      adults. Proteomic data are consistent with the RNA-Seq results and further
      suggest the lack of X upregulation at the protein level. Together, our findings
      reject Ohno's hypothesis, necessitating a major revision of the current model of
      dosage compensation in the evolution of sex chromosomes.

PMID- 21102463
TI  - Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease
      susceptibility loci.
AB  - We undertook a meta-analysis of six Crohn's disease genome-wide association
      studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls
      and followed up the top association signals in 15,694 cases, 14,026 controls and
      414 parent-offspring trios. We identified 30 new susceptibility loci meeting
      genome-wide significance (P < 5 * 10-8). A series of in silico analyses
      highlighted particular genes within these loci and, together with manual
      curation, implicated functionally interesting candidate genes including SMAD3,
      ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with
      previously confirmed loci, these results identify 71 distinct loci with genome
      wide significant evidence for association with Crohn's disease.

PMID- 21102466
TI  - Towards full-structure determination of bimetallic nanoparticles with an
      aberration-corrected electron microscope.
AB  - To fully understand the properties of functional nanostructures such as catalytic
      nanoclusters, it is necessary to know the positions of all the atoms in the
      nanostructure. The catalytic properties of metal nanoclusters can often be
      improved by the addition of a second metal, but little is known about the role of
      the different metals in these bimetallic catalysts, or about their interactions
      with each other and the support material. Here we show that aberration-corrected
      scanning transmission electron microscopy of supported rhodium-iridium clusters,
      combined with dynamic multislice image simulations, can identify individual
      atoms, map the full structure, and determine changes in the positions of metal
      atoms in sequential images. This approach could help in the development of new
      and improved catalysts and other functional nanostructures.

PMID- 21102465
TI  - The emerging field of RNA nanotechnology.
AB  - Like DNA, RNA can be designed and manipulated to produce a variety of different
      nanostructures. Moreover, RNA has a flexible structure and possesses catalytic
      functions that are similar to proteins. Although RNA nanotechnology resembles DNA
      nanotechnology in many ways, the base-pairing rules for constructing
      nanoparticles are different. The large variety of loops and motifs found in RNA
      allows it to fold into numerous complicated structures, and this diversity
      provides a platform for identifying viable building blocks for various
      applications. The thermal stability of RNA also allows the production of
      multivalent nanostructures with defined stoichiometry. Here we review techniques
      for constructing RNA nanoparticles from different building blocks, we describe
      the distinct attributes of RNA inside the body, and discuss potential
      applications of RNA nanostructures in medicine. We also offer some perspectives
      on the yield and cost of RNA production.

PMID- 21102467
TI  - The proliferation of nano journals.

PMID- 21102462
TI  - Thirty new loci for age at menarche identified by a meta-analysis of genome-wide
      association studies.
AB  - To identify loci for age at menarche, we performed a meta-analysis of 32 genome
      wide association studies in 87,802 women of European descent, with replication in
      up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 * 10-60) and
      9q31.2 (P = 2.2 * 10-33), we identified 30 new menarche loci (all P < 5 * 10-8)
      and found suggestive evidence for a further 10 loci (P < 1.9 * 10-6). The new
      loci included four previously associated with body mass index (in or near FTO,
      SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy
      homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in
      hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment
      pathway analyses identified coenzyme A and fatty acid biosynthesis as biological
      processes related to menarche timing.

PMID- 21102468
TI  - Length scaling of carbon nanotube transistors.
AB  - Carbon nanotube field-effect transistors are strong candidates in replacing or
      supplementing silicon technology. Although theoretical studies have projected
      that nanotube transistors will perform well at nanoscale device dimensions, most
      experimental studies have been carried out on devices that are about ten times
      larger than current silicon transistors. Here, we show that nanotube transistors
      maintain their performance as their channel length is scaled from 3 um to 15 nm,
      with an absence of so-called short-channel effects. The 15-nm device has the
      shortest channel length and highest room-temperature conductance (0.7G0) and
      transconductance (40 uS) of any nanotube transistor reported to date. We also
      show the first experimental evidence that nanotube device performance depends
      significantly on contact length, in contrast to some previous reports. Data for
      both channel and contact length scaling were gathered by constructing multiple
      devices on a single carbon nanotube. Finally, we demonstrate the performance of a
      nanotube transistor with channel and contact lengths of 20 nm, an on-current of
      10 uA, an on/off current ratio of 1 x 105, and peak transconductance of 20 uS.
      These results provide an experimental forecast for carbon nanotube device
      performance at dimensions suitable for future transistor technology nodes.

PMID- 21102469
TI  - Prephenate aminotransferase directs plant phenylalanine biosynthesis via
      arogenate.
AB  - The aromatic amino acids L-phenylalanine and L-tyrosine and their plant-derived
      natural products are essential in human and plant metabolism and physiology. Here
      we identified Petunia hybrida and Arabidopsis thaliana genes encoding prephenate
      aminotransferases (PPA-ATs), thus completing the identification of the genes
      involved in phenylalanine and tyrosine biosyntheses. Biochemical and genetic
      characterization of enzymes showed that PPA-AT directs carbon flux from
      prephenate toward arogenate, making the arogenate pathway predominant in plant
      phenylalanine biosynthesis.

PMID- 21102471
TI  - Predictors of pain resolution after varicocelectomy for painful varicocele.
AB  - Varicocelectomy is a management option for patients with painful varicocele. In
      this study, we assessed the effectiveness of varicocelectomy for painful
      varicocele and examined the factors that might be predictive of outcome. All
      patients who underwent a varicocelectomy for pain between February 2007 and July
      2009 were included. A review of patient medical records was conducted; patient
      age, body mass index (BMI), grade, location of the varicocele, testicular volume,
      duration and quality of the pain (dull, dragging, throbbing or sharp) and
      surgical technique (inguinal versus subinguinal) were documented. All parameters
      were compared with the resolution of pain (complete, partial or failure). We
      followed up on 53 of 104 patients (51.0%). Complete postoperative resolution of
      pain was reported by 28 patients (52.8%), whereas 22 (41.5%) reported partial
      resolution. Only three patients (5.7%) reported failure. No relationship was
      observed between postoperative pain resolution and age, BMI, grade of varicocele,
      location of varicocele, ipsilateral testicular hypotrophy, quality of pain or
      surgical technique. The duration of pain before surgery was the only factor that
      correlated with postoperative pain resolution (univariate, P=0.004; multivariate,
      P=0.002). Our results indicate that varicocelectomy is an effective treatment for
      painful varicocele in properly selected patients, and that duration of pain
      before surgery may be predictive of outcome.

PMID- 21102470
TI  - Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit.
AB  - Many protein kinases are key nodal signaling molecules that regulate a wide range
      of cellular functions. These functions may require complex spatiotemporal
      regulation of kinase activities. Here, we show that protein kinase A (PKA),
      Ca(2+) and cyclic AMP (cAMP) oscillate in sync in insulin-secreting MIN6 beta
      cells, forming a highly integrated oscillatory circuit. We found that PKA
      activity was essential for this oscillatory circuit and was capable of not only
      initiating the signaling oscillations but also modulating their frequency,
      thereby diversifying the spatiotemporal control of downstream signaling. Our
      findings suggest that exquisite temporal control of kinase activity, mediated via
      signaling circuits resulting from cross-regulation of signaling pathways, can
      encode diverse inputs into temporal parameters such as oscillation frequency,
      which in turn contribute to proper regulation of complex cellular functions in a
      context-dependent manner.

PMID- 21102472
TI  - Growth inhibition properties of the putative prostate cancer biomarkers PSP94 and
      CRISP-3.

PMID- 21102473
TI  - Pentoxifylline treatment and penile calcifications in men with Peyronie's
      disease.
AB  - This retrospective cohort study from a single clinical practice enrolled patients
      with evidence of calcified Peyronie's disease (PD) plaques detected on penile
      ultrasound at the time of initial presentation. The primary objective was to
      describe the effect of pentoxifylline (PTX) treatment on subtunical
      calcifications in men with PD. A PD-specific questionnaire was administered and
      sonographic evaluations were performed at baseline and follow-up visits.
      Descriptive statistics and chi(2) analysis were used to characterize the effect
      of PTX on calcified tunical plaques. In all, 71 men (mean age: 51.9 years) with
      PD and sonographic evidence of calcification were identified. Of them, 62 of
      these men were treated with PTX for a mean duration of 1 year, and nine with
      vitamin E or no treatment. Improvement or stabilization in calcium burden at
      follow-up was noted in 57 (91.9%) of men treated with PTX versus four (44.4%) of
      those not treated with PTX (P<0.001). PTX users were much less likely to have a
      subjective worsening of their clinical condition (25.0% versus 78.3%, P=0.002).
      Treatment with PTX appeared to stabilize or reduce calcium content in PD plaques.
      A randomized controlled trial is warranted to further explore this effect.

PMID- 21102474
TI  - Serum prostate-specific antigen value adjusted for non-cancerous prostate tissue
      volume in patients undergoing radical prostatectomy: a new predictor of
      biochemical recurrence in localized or locally advanced prostate cancer.
AB  - The aim of this study was to investigate the significance of serum prostate
      specific antigen (PSA) value adjusted for total tumor volume (PSA/tumor volume)
      and serum PSA value adjusted for non-cancerous prostate tissue volume (NCPV)
      (PSA/NCPV) as a predictor of pathological findings and clinical outcome after
      radical prostatectomy. Clinical and pathological data of 407 patients (median
      age: 66.5 years; range: 41.8-85.7 years) were reviewed retrospectively. The
      median follow-up period was 18.1 months (range: 1.0-107.8 months). Biochemical
      recurrence was defined as detectable PSA levels (greater than 0.2 ng ml(-1)) and
      the time of biochemical recurrence was taken to be the first time PSA became
      detectable. In the multivariate model, PSA/NCPV was an independent predictor of
      extracapsular extension and positive surgical margin (P<0.05), but PSA/tumor
      volume was not. Kaplan-Meier curves revealed that PSA/NCPV correlated with
      biochemical recurrence-free survival (P<0.001; log-rank test) but PSA/tumor
      volume did not (P=0.275; log-rank test). PSA/NCPV was also a significant
      independent prognostic factor for biochemical recurrence-free survival on
      multivariate Cox proportional hazard analysis (P=0.004, relative risk=2.42). Our
      findings suggest that PSA/NCPV is associated independently with extracapsular
      extension and surgical margin status and may be an independent prognostic
      variable of PSA recurrence after radical prostatectomy.

PMID- 21102475
TI  - An old emperor finds new clothing: rejuvenation in our time.

PMID- 21102476
TI  - CAG-repeat variant in the polymerase gamma gene and male infertility in the
      Chinese population: a meta-analysis.
AB  - Several studies have reported a relationship between the length of the CAG-repeat
      in the polymerase gamma (POLG) gene and male infertility. However, other studies
      have not reproduced this result. In our study, the POLG-CAG-repeat length was
      analyzed in 535 healthy individuals from six Chinese Han populations living in
      different provinces. The frequencies of 10-CAG alleles and genotypes were high
      (97.38 and 94.13%, respectively), with no significant difference among the six
      Chinese Han populations. Furthermore, we determined the distribution of the POLG
      CAG-repeat in 150 infertile men and 126 fertile men. Our study suggested that the
      distributions of POLG-CAG-repeat alleles and genotypes were not significantly
      different between infertile (95.67 and 92.67%, respectively) and fertile men
      (97.22 and 94.44%, respectively). In a subsequent meta-analysis, combining our
      data with data from previous studies, a comparison of the CAG-repeat alleles in
      fertile versus infertile men showed no obvious risk for male infertility
      associated with any particular allele (pooled odds ratio (OR)=0.94; 95%
      confidence interval (CI): 0.60-1.48). The significance level was not attained
      with any of the following genetic models: homozygote comparison (not 10/not 10
      versus 10/10: OR=1.34; 95% CI: 0.66-2.72), heterozygote comparison (10/not 10
      versus 10/10: OR=1.04; 95% CI: 0.78-1.38), dominant model comparison (not 10/not
      10+10/not 10 versus 10/10: OR=1.08; 95% CI: 0.79-1.47) and recessive genetic
      comparison (not 10/not 10 versus 10/not 10+10/10: OR=1.31; 95% CI: 0.68-2.55). In
      conclusion, there is no significant difference of the frequencies of POLG-CAG
      repeat variants among six Chinese Han populations, and this polymorphism may not
      be associated with Chinese male infertility. On the basis of a meta-analysis,
      there is no obvious association between CAG-repeat variants of the POLG gene and
      male infertility.

PMID- 21102477
TI  - Sperm cell biology: current perspectives and future prospects.

PMID- 21102478
TI  - Diagnostic tools in male infertility-the question of sperm dysfunction.
AB  - Sperm dysfunction is the single most common cause of infertility, yet what is
      remarkable is that, there is no drug a man can take or add to his spermatozoa in
      vitro to improve fertility. One reason for the lack of progress in this area is
      that our understanding of the cellular and molecular workings of the mature
      spermatazoon is limited. However, over the last few years there has been
      considerable progress in our knowledge base and in addressing new methods to
      diagnose sperm dysfunction. We review the current state of the field and provide
      insights for further development. We conclude that: (i) there is little to be
      gained from more studies identifying/categorizing various populations of men
      using a basic semen assessment, where an effort is required in making sure the
      analysis is performed in an appropriate high quality way; (ii) technological
      development is likely to bring the reality of sperm function testing closer to
      implementation into the clinical pathways. In doing this, these assays must be
      robust, cheap (or more appropriately termed cost effective), easy to use and
      clinically useful; and (iii) clinical necessity, e.g., the need to identify the
      highest quality spermatozoon for injection is driving basic research forward.
      This is an exciting time to be an andrologist and, likely, a fruitful one.

PMID- 21102479
TI  - Tanshinone IIA attenuates angiotensin II-induced apoptosis via Akt pathway in
      neonatal rat cardiomyocytes.
AB  - AIM: to examine the effects of tanshinone IIA, the main effective component of
      Salvia miltiorrhiza (known as 'Danshen' in traditional Chinese medicine) on
      angiotensin II (Ang II)-mediated cardiomyocyte apoptosis. METHODS: rat neonatal
      cardiomyocytes were primarily cultured with Ang II or Ang II plus tanshinone IIA.
      Myocyte apoptosis was evaluated by caspase-3 activity and DNA strand break level
      with TdT-mediated dUTP nick-end labeling (TUNEL) staining. Western blot analysis
      was employed to determine the related protein expression and flow cytometry assay
      was used to determine the TUNEL positive cells and the intracellular reactive
      oxygen species (ROS) production. SiRNA targeted to Akt was used. RESULTS: ang II
      (0.1 micromol/L) remarkably increased caspase-3 activity, TUNEL positive cells,
      and cleaved caspase-3 and cytochrome c expression, but reduced Bcl-X(L)
      expression. These effects were effectively antagonized by pretreatment with
      tanshione IIA (1-3 micromol/L). Tanshinone IIA had no effect on basal ROS level,
      while attenuated the ROS production by Ang II. Interestingly, tanshione IIA
      significantly increased the phosphorylated Akt level, which was countered by the
      PI3K antagonist wortmannin or LY294002. Knockdown of Akt with Akt siRNA
      significantly reduced Akt protein levels and tanshinone IIA protective effect.
      CONCLUSION: tanshinone IIA prevents Ang II-induced apoptosis, thereby suggesting
      that tanshinone IIA may be used for the prevention of the cardiac remodeling
      process.

PMID- 21102480
TI  - Potency of nondepolarizing muscle relaxants on muscle-type acetylcholine
      receptors in denervated mouse skeletal muscle.
AB  - AIM: to investigate the changing resistance to nondepolarizing muscle relaxants
      (NDMRs) during the first month after denervation. METHODS: the denervated and
      innervated skeletal muscle cells were examined on days 1, 4, 7, 14, 21, and 28
      after denervation. Individual denervated and innervated cells were prepared from
      the flexor digitorum brevis of the surgically denervated and contralateral hind
      feet, respectively. Nicotinic acetylcholine receptors (nAChRs) in the cells were
      activated with 30 micromol/L acetylcholine, either alone or in combination with
      various concentrations of vecuronium. Currents were recorded using a whole-cell
      patch-clamp technique. RESULTS: the concentrations of vecuronium resulting in
      half-maximal inhibitory responses (IC(50)) increased 1.2- (P>0.05), 1.7-, 3.7-,
      2.5-, 1.9-, and 1.8-fold (P<0.05) at Days 1, 4, 7, 14, 21, and 28 after
      denervation, respectively, compared to the innervated control. Resistance to
      vecuronium appeared at Day 4, peaked at Day 7, and declined at Day 14 after
      denervation. Nevertheless, IC(50) values at Day 28 remained significantly higher
      than those for the innervated control, suggesting that the resistance to
      vecuronium had not disappeared at Day 28. CONCLUSION: The NDMR doses required to
      achieve satisfactory clinical effects differ at different times after muscle
      denervation.

PMID- 21102481
TI  - Sorafenib extends the survival time of patients with multiple recurrences of
      hepatocellular carcinoma after liver transplantation.
AB  - AIM: to determine the efficacy and toxicities of sorafenib in the treatment of
      patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver
      transplantation in a Chinese population. METHODS: twenty patients with multiple
      recurrences of HCC after liver transplantation were retrospectively studied. They
      received either transarterial chemoembolization (TACE) or TACE combined with
      sorafenib. RESULTS: the median survival times (MST) after multiple recurrences
      was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The
      difference was significant in MST between the two groups (P=0.005). The TACE +
      sorafenib group had more stable disease (SD) patients than the TACE group. The
      most frequent adverse events of sorafenib were hand-foot skin reaction and
      diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are
      found to be significantly associated with tumor-free survival time, the survival
      time after multiple recurrences and overall survival time. TACE+sorafenib group
      showed a better outcome than single TACE treatment group. In the multivariate COX
      regression modeling, the preoperative high CHILD grade was found to be a risk
      factor of tumor-free survival time. In addition, the preoperative high bilirubin
      grade was also found to be a risk factor of survival time after recurrence and
      overall survival time. Furthermore, survival time after recurrence and overall
      survival time were also associated with therapeutic schedule, which was indicated
      by the GROUP. CONCLUSION: Treatment with TACE and sorafenib is worthy of further
      study and may have more extensive application prospects.

PMID- 21102482
TI  - Involvement of Bcl-2, Src, and ERalpha in gossypol-mediated growth inhibition and
      apoptosis in human uterine leiomyoma and myometrial cells.
AB  - AIM: to investigate the effect of gossypol on the growth of cultured human
      uterine leiomyoma and myometrial cells, the level of Bcl-2 and the activity of
      Src and estrogen receptor (ERalpha). METHODS: human uterine leiomyoma and
      adjacent normal myometrial cells were cultured in vitro. Both cell types were
      treated with a graded concentration of gossypol. Cell viability was assayed using
      CCK-8. Morphological change was observed with optical and electronic microscopy.
      Apoptosis was evaluated using TUNEL assay. Levels of Bcl-2, ERalpha and Src were
      analyzed using Western blotting. RESULTS: gossypol significantly inhibited growth
      and promoted apoptosis in cultured human uterine leiomyoma cells with the IC(50)
      value and its corresponding 95% confidence intervals (CI) of 6.5 (4.0-10.5), 9.0
      (4.9-16.5), and 7.5 (4.0-14.1) micromol/L at 20, 40, and 60 h, respectively.
      Gossypol exerted inhibitory effects on the myometrial cells with the IC(50) value
      and its 95% CI of 49.1 (28.3-85.0), 14.5 (7.7-27.4), and 2.6 (1.2-5.6) micromol/L
      at 20, 40, and 60 h, respectively. Compared with control, gossypol 0.1-3.0
      micromol/L markedly decreased the protein expression of Bcl-2 (P<0.05) in both
      leiomyoma and myometrial cells in a concentration-dependent manner, and
      significantly suppressed the level of phospho-Tyr416Src (P<0.05) in both cell
      types at 3.0 micromol/L without obvious alteration of c-Src and phospho-Tyr527Src
      levels (P>0.05). In addition, gossypol markedly reduced both the expression of
      ERalpha (P<0.05) at the low concentration of 0.1 micromol/L in the myometrial
      cells and the level of phospho-ser167ERalpha (P<0.05) at the high concentration
      of 3.0 MUmol/L in the leiomyoma cells. CONCLUSION: gossypol inhibits
      proliferation and induces apoptosis in human uterine leiomyoma and myometrial
      cells. It is likely that the mechanisms of action involve reducing the protein
      level of Bcl-2 and the activity of Src and ERalpha.

PMID- 21102483
TI  - A high-throughput screening system for G-protein-coupled receptors using beta
      lactamase enzyme complementation technology.
AB  - AIM: to establish a system for monitoring the activation of G-protein-coupled
      receptors (GPCRs) using beta-lactamase enzyme fragment complementation (EFC)
      technology. METHODS: two inactive beta-lactamase deletion fragments, bla(a) and
      bla(b), were fused to beta-arrestin and GPCR, respectively. A stable cell line
      named HEK/293-beta2a2, which expressed two fusion proteins, GPCR/bla(b) and beta
      arrestin2/bla(a), was generated under antibiotic selection. A natural compound
      library of high performance liquid chromatography (HPLC)-fractionated samples
      from the ethanol extracts of Chinese medicinal herbs was used for high-throughput
      screening (HTS) of beta2-adrenoceptor (beta2AR) agonists against the cell line
      HEK/293-beta2a2. The interested hits were validated by the measurement of second
      messenger cyclic adenosine monophosphate (cAMP) production. RESULTS: the stable
      cell line HEK/293-beta2a2 responded to beta2AR agonist/antagonist in a dose
      dependent manner. The EC(50) value obtained for isoproterenol was 15.5 nmol/L,
      and the IC(50) value obtained for propranolol was 51.9 nmol/L. Furthermore, HTS
      was performed to identify beta2AR agonists from the natural compound library we
      established. The Z' factor value was determined to be 0.68. Three hits were
      identified from primary screening and found to be as potent as isoproterenol in a
      camp assay. CONCLUSION: a cell-based high-throughput functional assay was
      established to directly monitor the activation of GPCRs based on the interaction
      between agonist-activated GPCR and beta-arrestin using beta-lactamase EFC
      technology, which can be used to search for leads in the natural compound
      library.

PMID- 21102484
TI  - Effects of ATPM-ET, a novel kappa agonist with partial MU activity, on physical
      dependence and behavior sensitization in mice.
AB  - AIM: to investigate the effects of ATPM-ET [(-)-3-N-Ethylaminothiazolo [5,4-b]-N
      cyclopropylmethylmorphinan hydrochloride] on physical dependence and behavioral
      sensitization to morphine in mice. METHODS: the pharmacological profile of ATPM
      ET was characterized using competitive binding and GTPgammaS binding assays. We
      then examined the antinociceptive effects of ATPM-ET in the hot plate test.
      Morphine dependence assay and behavioral sensitization assay were used to
      determine the effect of ATPM-ET on physical dependence and behavior sensitization
      to morphine in mice. RESULTS: the binding assay indicated that ATPM-ET ATPM-ET
      exhibited a high affinity to both kappa- and MU-opioid receptors with K(i) values
      of 0.15 nmol/L and 4.7 nmol/L, respectively, indicating it was a full kappa
      opioid receptor agonist and a partial MU-opioid receptor agonist. In the hot
      plate test, ATPM-ET produced a dose-dependent antinociceptive effect, with an
      ED(50) value of 2.68 (2.34-3.07) mg/kg. Administration of ATPM-ET (1 and 2 mg/kg,
      sc) prior to naloxone (3.0 mg/kg, sc) injection significantly inhibited
      withdrawal jumping of mice. In addition, ATPM-ET (1 and 2 mg/kg, sc) also showed
      a trend toward decreasing morphine withdrawal-induced weight loss. ATPM-ET (1.5
      and 3 mg/kg, sc) 15 min before the morphine challenge significantly inhibited the
      morphine-induced behavior sensitization (P<0.05). CONCLUSION: ATPM-ET may have
      potential as a therapeutic agent for the treatment of drug abuse.

PMID- 21102485
TI  - Chronic ethanol consumption up-regulates protein-tyrosine phosphatase-1B (PTP1B)
      expression in rat skeletal muscle.
AB  - AIM: to investigate the potential effects of chronic ethanol intake on protein
      tyrosine phosphatase-1B (PTP1B) and the insulin receptor signaling pathway in rat
      skeletal muscle. METHODS: rats received ethanol treatment at a daily dose of 0
      (control), 0.5 (group L), 2.5 (group M) or 5 gxkg(-1) (group H) via gastric
      gavage for 22 weeks. In vivo insulin sensitivity was measured using a
      hyperinsulinemic-euglycemic clamp. Expression of PTP1B in skeletal muscles was
      examined at both the mRNA (real-time PCR) and protein (Western blot) levels.
      PTP1B activity was assayed with a p-nitrophenol phosphate (PNPP) hydrolysis
      method. Changes of insulin signaling in skeletal muscle were analyzed with
      Western blotting. RESULTS: the activity and expression of PTP1B were dose
      dependently elevated 1.6 and 2.0 fold in the skeletal muscle by ethanol,
      resepctively, at the doses of 2.5 and 5 gxkg(-1)xd(-1). Total IRbeta and IRS-1,
      as well as their phosphorylated forms, were decreased by ethanol at the two
      higher doses. Moreover, chronic ethanol consumption resulted in a significant
      inhibition of the association between IRS-1 and the p85 subunit of
      phosphatidylinositol 3-kinase, inhibition of Akt phosphorylation and reduced
      levels of mitogen-activated protein kinase phosphorylation. CONCLUSION: chronic
      ethanol intake at 2.5 and 5 xkg(-1)xd(-1) sufficient doses can down-regulate the
      expression of IRbeta, P-IRbeta, and IRS-1, as well as the phosphorylated forms of
      IRS-1 and Akt, in rat skeletal muscle, possibly through increased PTP1B activity.

PMID- 21102488
TI  - Measurement of intraocular pressure in children in the UK.

PMID- 21102486
TI  - World Rabies Day: a prime role for veterinarians in rabies control.

PMID- 21102489
TI  - Visible iris sign as a predictor of problems during and following anterior
      approach ptosis surgery.
AB  - OBJECTIVE: To describe the pre- and postoperative features of the visible iris
      sign (VIS), which is the apparent visibility of iris colour through a closed
      upper eyelid, in patients undergoing anterior approach surgery for severe
      involutional aponeurotic ptosis, and to assess its effect on postoperative
      outcome. DESIGN: Prospective, comparative interventional case series. METHODS:
      Prospective series of all patients undergoing surgery for severe involutional
      aponeurotic ptosis during a 16-month period at a single centre. INCLUSION
      CRITERIA: Severe involutional ptosis (upper eyelid margin reflex distance (MRD)
      <=1 mm) treated by anterior-approach surgery. MAIN OUTCOME MEASURES: Presence of
      VIS, type of ptosis (primary or recurrent), preoperative MRD, levator function
      and skin crease height, documented unusual intra-operative findings,
      postoperative complications, and follow-up time. RESULTS: Of 133 procedures for
      involutional aponeurotic ptosis, 96 procedures (56 patients) were included in the
      study. In total, 12 patients (21%, 12/56, 2 males, and 10 females) had been
      identified as having VIS preoperatively. In order to avoid any selection bias,
      only patients with severe degree of ptosis were included in the two groups with
      the two groups being alike in the preoperative lid height, levator function or
      the skin crease. In the VIS group, 55% (12/22) had a thinned, significantly
      retracted levator aponeurosis and a thin tarsus prone to full-thickness suture
      passes (36.3%, 8/22) during aponeurosis reattachment. Immediate persistent
      overcorrection during surgery was seen in three procedures, with one patient
      having an under corrected outcome when treated with a hang-back suture. In the
      non-VIS group, no patients were documented intra-operatively, as having
      significant retraction of the levator aponeurosis. However, 14% (10/74) of the
      eyelids were recorded as having a very attenuated levator and one patient (3%,
      1/44) was noted to have a floppy tarsus that was difficult to suture. The total
      incidence of intra-operative difficulties during surgery were 78% in the VIS
      group and 22% in the non-VIS group. Mean postoperative follow-up was 22 weeks.
      (median 18, range 12-64). The overall success rates were 63.6% (14/22) in the VIS
      group, compared with 77.0% (57/74) in the non-VIS group (P = 0.260). After
      excluding cases undergoing concurrent blepharoplasty and non-Caucasians, success
      rates were 57.1% (4/7) and 69.2% (9/13) in the VIS and non-VIS groups,
      respectively (P = 0.598). All failures were because of under-correction.
      CONCLUSION: The VIS is a clinical sign of severe involutional ptosis. Patients
      with VIS have one or more features, including a retracted levator aponeurosis, a
      thinned tarsus prone to full-thickness suture passes, and a tendency for
      immediate persistent overcorrection following levator advancement. Preoperative
      identification of VIS may help in appropriate patient counselling, procedure
      selection, anticipation of intraoperative difficulties, and possibly further
      standardisation of future cohorts when evaluating the results of involutional
      ptosis surgery. PRECIS: The authors describe the pre-, intra- and postoperative
      features of visible iris sign. They discuss the success rates of anterior
      approach surgery in VIS patients and discuss the contributing factors for a
      poorer outcome.

PMID- 21102490
TI  - Recurrent iris prolapse after laser goniopuncture in an open-angle glaucoma
      patient treated with non-penetrating trabecular surgery.

PMID- 21102491
TI  - Mapping the visual brain: how and why.
AB  - Over the past 15 years, techniques for identifying visual areas using magnetic
      resonance imaging (MRI) in human subjects have been applied widely to multiple
      populations. This review will cover the basic techniques of using functional MRI
      and very high-resolution structural MRI to determine boundaries between different
      areas of the visual cortex. Recent applications of these methods to
      ophthalmological patient populations are discussed, and the future potential
      applications of very high field strength MRI are considered.

PMID- 21102492
TI  - Comparing fixation location and stability in patients with neovascular age
      related macular degeneration treated with or without Ranibizumab.
AB  - PURPOSE: To compare fixation location and stability in patients with neovascular
      age-related macular degeneration (AMD) treated with or without ranibizumab.
      METHODS: Patients were recruited from the Macular Clinic of the King's College
      Hospital in London. Two groups of patients with neovascular AMD with at least 12
      months of follow-up were included in the study. The treated group was treated
      with ranibizumab while the untreated group did not have any treatment. Best
      corrected visual acuity (BCVA) with modified ETDRS chart, fixation location and
      stability as measured with Nidek MP1, central retinal thickness as measured by
      Zeiss Cirrus SD-optical coherent tomography (OCT), and lesion size as measured by
      Topcon TRC-50IX camera were analysed and correlated. RESULTS: In total, 102 eyes
      were included in the study with 76 in the ranibizumab-treated group and 26 in the
      untreated group. There were no significantly demographic differences between the
      two groups. However, as expected, the treated group has significantly better
      vision (48.5 vs 15.5 letters, P < 0.0001) and smaller lesions (10.8 vs 18.3
      mm(2), P = 0.004), the central macular thickness as measured by OCT also showed a
      trend of normalised macular thickness (252 vs 282 microns, P = 0.07). The
      location of fixation was significantly more central in the ranibizumab-treated
      group (chi(2) 17.9, P < 0.0001) with over 50% of eyes with predominantly central
      fixation. Majority (84.6%) of the patients in the untreated group had
      predominantly eccentric fixation. Fixation stability was significantly better in
      the ranibizumab-treated group as compared with the untreated group, using both
      the software provided by the MP1 machine (chi(2) 21.8, P < 0.0001) and the mean
      log bivariate contour ellipse area calculated from the raw data obtained from the
      machine (3.64 vs 4.39 in treated and untreated group respectively, P < 0.0001).
      CONCLUSION: Low vision rehabilitation strategy for this group of patients in the
      ranibizumab era will be very different from those used in untreated patients with
      dense central scotoma. Further studies on the visual rehabilitation in the
      ranibizumab-treated patients should consider fixation characteristics of the
      patients.

PMID- 21102493
TI  - The efficacy of intravenous ketorolac for pain relief in single-stage adjustable
      strabismus surgery: a prospective, randomized, placebo-controlled trial.
AB  - PURPOSE: To determine the efficacy of preoperative intravenous ketorolac in
      reducing intraoperative and postoperative pain and improving patient satisfaction
      in patients undergoing single-stage adjustable strabismus surgery. METHODS: A
      prospective, randomized, placebo-controlled clinical trial was performed with 67
      patients who underwent horizontal recti muscle surgery with adjustable sutures.
      The test group received intravenous ketorolac (60 mg) before surgery, and the
      control group received intravenous normal saline. Topical 0.5% proparacaine was
      administered to both groups during surgery. Vital signs including heart rate and
      blood pressure were recorded every 10 min throughout the surgery. The patients
      were asked to rate their maximum intraoperative and postoperative pain scores
      using a numerical pain rating scale. Patient satisfaction was also assessed using
      a five-point analogue scale. RESULTS: The ketorolac-premedicated patients had
      less pain both during and after surgery (P = 0.033 and P = 0.024, respectively).
      There were no differences in vital signs during surgery and patient satisfaction
      between the two groups. CONCLUSIONS: Intravenous ketorolac, when administered
      preoperatively for single-stage adjustable strabismus surgery under topical
      anaesthesia, was effective in reducing pain during and after surgery.

PMID- 21102494
TI  - Frequency doubling technique perimetry and spectral domain optical coherence
      tomography in patients with early glaucoma.
AB  - PURPOSE: To assess the combined diagnostic power of frequency-doubling technique
      (FDT)-perimetry and retinal nerve fibre layer (RNFL) thickness measurements with
      spectral domain optical coherence tomography (SDOCT). METHODS: The study included
      330 experienced participants in five age-related groups: 77 'preperimetric' open
      angle glaucoma (OAG) patients, 52 'early' OAG, 50 'moderate' OAG, 54 ocular
      hypertensive patients, and 97 healthy subjects. For glaucoma assessment in all
      subjects conventional perimetry, evaluation of fundus photographs, FDT-perimetry
      and RNFL thickness measurement with SDOCT was done. Glaucomatous visual field
      defects were classified using the Glaucoma Staging System. FDT evaluation used a
      published method with casewise calculation of an 'FDT-score', including all
      missed localized probability levels. SDOCT evaluation used mean RNFL thickness
      and a new individual SDOCT-score considering normal confidence limits in 32
      sectors of a peripapillary circular scan. To examine the joined value of both
      methods a combined score was introduced. Significance of the difference between
      Receiver-operating-characteristic (ROC) curves was calculated for a specificity
      of 96%. RESULTS: Sensitivity in the preperimetric glaucoma group was 44% for
      SDOCT-score, 25% for FDT-score, and 44% for combined score, in the early glaucoma
      group 83, 81, and 89%, respectively, and in the moderate glaucoma group 94, 94,
      and 98%, respectively, all at a specificity of 96%. ROC performance of the newly
      developed combined score is significantly above single ROC curves of FDT-score in
      preperimetric and early OAG and above RNFL thickness in moderate OAG. CONCLUSION:
      Combination of function and morphology by using the FDT-score and the SDOCT-score
      performs equal or even better than each single method alone.

PMID- 21102495
TI  - Response to 'Inhibitory effects of maternal smoking on the development of severe
      retinopathy of prematurity'.

PMID- 21102496
TI  - Cotrimoxazole myelotoxicity in hematopoietic SCT recipients: time for
      reappraisal.

PMID- 21102497
TI  - The outcome of high-dose chemotherapy and auto-SCT in patients with multiple
      myeloma: a UK/Ireland and European benchmarking comparative analysis.
AB  - Auto-SCT is the standard first-line consolidative therapy in patients with
      multiple myeloma (MM). We performed a national benchmarking outcome analysis for
      patients with MM who underwent a single auto-SCT in 1999 and 2005. They were
      identified from the British Society of Blood and Marrow Transplantation (BSBMT)
      (n=211 and n=453) and EBMT (n=1311 and n=1978) registries. An improvement in
      Day+100 and D+365 non-relapsed mortality (NRM) was shown between years 1999 and
      2005 (P=0.0495). The 4-year relapse rate (RR) was significantly higher in 2005
      (P=0.0003) and was associated with a shorter time to next treatment (TTNT)
      (P=0.025). The 4-year PFS was significantly lower in 2005 (P=0.0012), with the
      year of auto-SCT (P=0.001) and status at auto-SCT (P=0.02) being independently
      significant. The 4-year OS was similar between the year cohorts (P=0.266). In the
      'benchmarking' comparison, the European Group for Blood and Marrow
      Transplantation (EBMT) 1999 cohort demonstrated the best PFS, although no year-of
      transplant effect could be demonstrated on the 4-year OS rates (P=0.760). An
      improvement in supportive care resulting in reduced NRM is evident between the
      decades. The main cause of treatment failure remains disease progression. The
      similarity in OS between the years may reflect the introduction of novel agents
      in salvage therapy. The reduced PFS in 2005 is as yet not fully explained, but
      may represent recent disease response criterion standardization.

PMID- 21102498
TI  - Cytochrome P450 genetic polymorphisms influence the serum concentration of
      calcineurin inhibitors in allogeneic hematopoietic SCT recipients.
AB  - Calcineurin inhibitors are necessary as immunosuppressants during hematopoietic
      SCT (HSCT) to prevent alloreactivity, but have unfortunate toxicities. So, we
      investigated the association of gene polymorphisms with the initial calcineurin
      inhibitor concentration and the subsequent drug dose from day 1 to day 28 among
      patients who underwent HSCT at a single institution. We analyzed 58 serial cases
      of Japanese patients receiving GVHD prophylaxis with CsA (21 cases) or tacrolimus
      (37 cases). We investigated eight single-nucleotide polymorphisms: rs4244285
      (CYP2C19), rs15524, rs4646450, rs3800959, rs776746 (CYP3A5), rs1128503, rs2032582
      and rs1045642 (MDR1). The CsA concentration was significantly higher when the
      genotype of CYP3A5 rs15524 was T/T (P=0.044) or rs776746 was G/G (P=0.027). The
      CYP3A5 rs776746 and rs4646450 genotypes were also associated with tacrolimus
      concentration (P=0.013 and P=0.0058, respectively). The dosage of tacrolimus was
      remarkably reduced from day -1 to day 28 when the patient had the CYP3A5
      rs4646450 C/C and/or rs776746 G/G genotype (P=0.0010 and P=0.0021, respectively).
      In this study, we show that genetic variation has a predictable effect on the
      pharmacological responses to calcineurin inhibitors in HSCT patients.

PMID- 21102499
TI  - Pre-SCT serum ferritin is a prognostic factor in adult AML, but not ALL.

PMID- 21102500
TI  - Plerixafor is effective and safe for stem cell mobilization in heavily pretreated
      germ cell tumor patients.
AB  - Up to 10% of germ cell tumor patients require salvage high-dose chemotherapy with
      stem cell support, achieving cure rates in the range of 10-60%. Stem cell
      mobilization may be difficult in these patients because of multiple lines of
      treatment known to seriously hamper stem cell recovery. Plerixafor significantly
      enhances the success of the CD34+ cell harvest, even in cases where prior
      mobilization attempts have failed. Six germ cell tumor patients provided informed
      consent and were included in the compassionate use program. All patients were
      heavily pretreated, with a median of 3.5 prior lines of therapy. All failed prior
      mobilization with G-CSF in combination with chemotherapy. Five patients yielded a
      median of 2.6 * 10(6) CD34+ cells per kg body weight in a median of 4 apheresis
      days when plerixafor was used. Three patients underwent subsequent high-dose
      chemotherapy with autologous stem cell support. Median time to leukocyte
      engraftment was 11 days. Median time to platelet engraftment was 12.5 days, both
      of which are comparable to previous historical data. Accordingly, plerixafor
      seems to be safe and effective in germ cell tumor patients who have failed prior
      mobilization therapy. Larger prospective studies are warranted to further assess
      its use in germ cell cancer.

PMID- 21102501
TI  - Hematopoietic stem cell transplantation in children with cancer and the risk of
      long-term psychological morbidity in the bereaved parents.
AB  - We have investigated whether hematopoietic stem cell transplantation (HSCT)
      before the death of children with cancer has a long-term effect on the physical
      and psychological well-being of the parents. A nationwide questionnaire was sent
      out to all bereaved parents in Sweden who had lost a child due to a malignancy
      from 1992 to 1997. Self-reported levels of anxiety, depression and quality of
      life as well as overall psychological and physical well-being in bereaved parents
      of children who underwent HSCT were compared with bereaved parents whose children
      did not receive a transplant. Bereaved parents whose children underwent HSCT had,
      according to a visual digital scale, an increased relative risk (RR) of long-term
      anxiety (RR 1.5; 95% confidence interval (CI) 1.0-2.1), poor psychological well
      being (RR1.3; 95% CI 1.1-1.5), low quality of life (RR 1.4; 95% CI 1.2-1.7) and
      poor physical health (RR 1.3; 95% CI 1.1-1.5), whereas the State-Trait Anxiety
      Inventory and 'The Goteborg Quality of Life Instrument' were non-significantly
      increased (RR 1.3; 95% CI 0.8-2.3 and RR 1.7; 95% CI 0.9-3.3, respectively). The
      risks of these consequences were further augmented in case of multiple HSCT. We
      suggest that bereaved parents of children undergoing HSCT may be at greater risk
      of decreased psychological well-being than other bereaved parents of children
      with cancer.

PMID- 21102502
TI  - Vaccination of SCT recipients.

PMID- 21102503
TI  - Temporal spatial expression and function of non-muscle myosin II isoforms IIA and
      IIB in scar remodeling.
AB  - Scar contracture is believed to be caused by the cell contractility during the
      remodeling phase of wound healing. Cell contractility is mediated by non-muscle
      myosin II (NMMII) and actin, but the temporal-spatial expression profile of NMMII
      isoforms A and B (IIA and IIB) during the remodeling phase and the role of NMMII
      in scar fibroblast tissue remodeling are unknown. Human scar tissue immunostained
      for IIA and IIB showed that both isoforms were highly expressed in scar tissue
      throughout the remodeling phase of repair and expression levels returned to
      normal after the remodeling phase. Human scar tissue immunostained for beta-,
      gamma- and alpha-smooth muscle actin showed that all isoforms were consistently
      expressed throughout the remodeling phase of repair. The beta- and gamma-smooth
      muscle actin were widely expressed throughout the dermis, but alpha-smooth muscle
      actin was only locally expressed within the dermis. In vitro, fibroblasts
      explanted from scar tissue were shown to express more IIA than fibroblasts
      explanted from normal tissue and scar fibroblasts contracted collagen lattices to
      a greater extent than normal fibroblasts. Blebbistatin was used to demonstrate
      the function of NMMII in collagen lattice contraction. In normal tissue,
      fibroblasts are stress-shielded from external tensile stress by the extracellular
      matrix. After dermal injury and during remodeling, fibroblasts are exposed to a
      matrix of increased stiffness. The effect of matrix stiffness on IIA and IIB
      expression was examined. IIA expression was greater in fibroblasts cultured in
      collagen lattices with increasing stiffness, and in fibroblasts cultured on glass
      slides compared with polyacrylamide gels with stiffness of 1 kPa. In conclusion,
      NMMII and actin isoform expression changes coordinately with the remodeling phase
      of repair, and NMMII is increased as matrix stiffness increases. As NMMII
      expression increases, so does the fibroblast contractility.

PMID- 21102504
TI  - Blockade of complement activation product C5a activity using specific antibody
      attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of
      colitis.
AB  - Complement represents a chief component of innate immunity in host defense.
      However, excessive complement activation has been involved in the pathogenesis of
      inflammatory diseases. In this study, we investigated the contribution of
      complement to intestinal pathology of patients and rodents with inflammatory
      bowel disease. The expression of complement effectors (C3a and C3) was increased
      remarkably in inflamed colons of IBD patients compared with those of normal
      counterparts. In accordance with this, the sustained activation of complement in
      serum and colon (including elevated C3a and C5a levels, enhanced hemolytic
      activity, downregulated expression of C5a receptors) was observed, following the
      establishment of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis,
      which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (-2,
      0, and 2 days after TNBS instillation) had significantly reduced weight loss and
      improved macroscopic/microscopic scores, comparable to the efficacy of
      prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS
      instillation showed remarkable therapeutic effects, whereas prednisolone did not.
      The efficacy of anti-C5a administration was associated with decreased release of
      proinflammatory chemokines and cytokines, inhibition of infiltration of
      neutrophils into colons, and enhanced Th2 response. These findings suggest a
      disease-promoting role of complement, particular C5a, in the pathology of TNBS
      induced colitis in mice, indicating possible therapeutic potentials for C5a
      specific antibody in IBD.

PMID- 21102505
TI  - Expression profiles of podocytes exposed to high glucose reveal new insights into
      early diabetic glomerulopathy.
AB  - Podocyte injury has been suggested to have a pivotal role in the pathogenesis of
      diabetic glomerulopathy. To glean insights into molecular mechanisms underlying
      diabetic podocyte injury, we generated temporal global gene transcript profiles
      of podocytes exposed to high glucose for a time interval of 1 or 2 weeks using
      microarrays. A number of genes were altered at both 1 and 2 weeks of glucose
      exposure compared with controls grown under normal glucose. These included
      extracellular matrix modulators, cell cycle regulators, extracellular
      transduction signals and membrane transport proteins. Novel genes that were
      altered at both 1 and 2 weeks of high-glucose exposure included neutrophil
      gelatinase-associated lipocalin (LCN2 or NGAL, decreased by 3.2-fold at 1 week
      and by 7.2-fold at 2 weeks), endothelial lipase (EL, increased by 3.6-fold at 1
      week and 3.9-fold at 2 week) and UDP-glucuronosyltransferase 8 (UGT8, increased
      by 3.9-fold at 1 week and 5.0-fold at 2 weeks). To further validate these
      results, we used real-time PCR from independent podocyte cultures,
      immunohistochemistry in renal biopsies and immunoblotting on urine specimens from
      diabetic patients. A more detailed time course revealed changes in LCN2 and EL
      mRNA levels as early as 6 hours and in UGT8 mRNA level at 12 hours post high
      glucose exposure. EL immunohistochemistry on human tissues showed markedly
      increased expression in glomeruli, and immunoblotting readily detected EL in a
      subset of urine samples from diabetic nephropathy patients. In addition to
      previously implicated roles of these genes in ischemic or oxidative stress, our
      results further support their importance in hyperglycemic podocyte stress and
      possibly diabetic glomerulopathy pathogenesis and diagnosis in humans.

PMID- 21102506
TI  - More than just room temperature.

PMID- 21102507
TI  - A window on the future of spintronics.

PMID- 21102508
TI  - A model ferromagnetic semiconductor. Interview by Fabio Pulizzi.

PMID- 21102509
TI  - Is it really intrinsic ferromagnetism? Interview by Fabio Pulizzi.

PMID- 21102511
TI  - Spintronics: Beyond the speed limit.

PMID- 21102512
TI  - Biomineralization: A crystal-clear view.

PMID- 21102513
TI  - Acoustics: Now you hear me, now you don't.

PMID- 21102514
TI  - Correlated electron systems: Reaching for the stars.

PMID- 21102515
TI  - Material witness: Fractal standstill.

PMID- 21102516
TI  - A ten-year perspective on dilute magnetic semiconductors and oxides.
AB  - Over the past ten years, the search for compounds combining the properties of
      semiconductors and ferromagnets has evolved into an important field of materials
      science. This endeavour has been fuelled by many demonstrations of remarkable low
      temperature functionalities in the ferromagnetic structures (Ga,Mn)As and p
      (Cd,Mn)Te, and related compounds, and by the theoretical prediction that
      magnetically doped, p-type nitride and oxide semiconductors might support
      ferromagnetism mediated by valence-band holes to above room temperature. Indeed,
      ferromagnetic signatures persisting at high temperatures have been detected in a
      number of non-metallic systems, even under conditions in which the presence of
      spin ordering was not originally anticipated. Here I review recent experimental
      and theoretical developments, emphasizing that they not only disentangle many
      controversies and puzzles accumulated over the past decade but also offer new
      research prospects.

PMID- 21102517
TI  - Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion
      through LPA1 receptor and MMP-9 expression.
AB  - Lysophosphatidic acid (LPA), produced extracellularly by autotaxin (ATX), has
      diverse biological activities implicated in tumor initiation and progression,
      including increasing cell survival, angiogenesis, invasion and metastasis. ATX,
      LPA and the matrix metalloproteinase (MMP)-9 have all been implicated in
      hepatocellular carcinoma (HCC) invasion and metastasis. We, thus sought to
      determine whether ATX with subsequent LPA production and action, including
      induction of MMP-9 could provide a unifying mechanism. ATX transcripts and LPA
      receptor type 1 (LPA1) protein are elevated in HCC compared with normal tissues.
      Silencing or pharmacological inhibition of LPA1 significantly attenuated LPA
      induced MMP-9 expression and HCC cell invasion. Further, reducing MMP-9 activity
      or expression significantly inhibits LPA-induced HCC cell invasion, demonstrating
      that MMP-9 is downstream of LPA1. Inhibition of phosphoinositide-3 kinase (PI3K)
      signaling or dominant-negative mutants of protein kinase Cdelta and p38 mitogen
      activated protein kinase (MAPK) abrogated LPA-induced MMP-9 expression and
      subsequent invasion. We thus demonstrate a mechanistic cascade of ATX-producing
      LPA with LPA activating LPA1 and inducing MMP-9 through coordinate activation of
      the PI3K and the p38 MPAK signaling cascades, providing novel biomarkers and
      potential therapeutic targets for HCC.

PMID- 21102518
TI  - Efficient in vivo microRNA targeting of liver metastasis.
AB  - Targeting oncogenic microRNAs (miRNAs) is emerging as a promising strategy for
      cancer therapy. In this study, we provide proof of principle for the safety and
      efficacy of miRNA targeting against metastatic tumors. We tested the impact of
      targeting miR-182, a pro-metastatic miRNA frequently overexpressed in melanoma,
      the in vitro silencing of which represses invasion and induces apoptosis.
      Specifically, we assessed the effect of anti-miR-182 oligonucleotides synthesized
      with 2' sugar modifications and a phosphorothioate backbone in a mouse model of
      melanoma liver metastasis. Luciferase imaging showed that mice treated with anti
      miR-182 had a lower burden of liver metastases compared with control. We
      confirmed that miR-182 levels were effectively downregulated in the tumors of
      anti-miR-treated mice compared with tumors of control-treated mice, both in the
      liver and in the spleen. This effect was accompanied by an upregulation of
      multiple miR-182 direct targets. Transcriptional profiling of tumors treated with
      anti-miR-182 or with control oligonucleotides revealed an enrichment of genes
      controlling survival, adhesion and migration modulated in response to anti-miR
      182 treatment. These data indicate that in vivo administration of anti-miRs
      allows for efficient miRNA targeting and concomitant upregulation of miRNA
      controlled genes. Our results demonstrate that the use of anti-miR-182 is a
      promising therapeutic strategy for metastatic melanoma and provide a solid basis
      for testing similar strategies in human metastatic tumors.

PMID- 21102520
TI  - Identifying LRRC16B as an oncofetal gene with transforming enhancing capability
      using a combined bioinformatics and experimental approach.
AB  - Oncofetal genes are expressed in embryos or fetuses, are downregulated or
      undetectable in adult tissues, and then re-expressed in tumors. Known oncofetal
      genes, such as AFP, GCB, FGF18, IMP-1 and SOX1, often have important clinical
      applications or pivotal biological functions. To find new oncofetal-like genes,
      we used the public information of expressed sequence tags to systematically
      analyze gene expression patterns and identified a novel oncofetal-like gene,
      LRRC16B. It increased the proliferation, anchorage-independent growth and
      tumorigenesis of transformed cells in xenografts, possibly through its effects on
      cyclin B1 protein levels. These findings exemplify the feasibility of using
      bioinformatics to find new oncofetal-like genes and suggest that more genes with
      important functional roles will be uncovered in the candidate gene list.

PMID- 21102519
TI  - MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to
      mesenchymal transition.
AB  - Increased motility and invasiveness of pancreatic cancer cells are associated
      with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger
      transcription factors that trigger this process by repressing E-cadherin and
      enhancing vimentin and N-cadherin protein expression. However, the mechanisms
      that regulate this activation in pancreatic tumors remain elusive. MUC1, a
      transmembrane mucin glycoprotein, is associated with the most invasive forms of
      pancreatic ductal adenocarcinomas (PDA). In this study, we show that over
      expression of MUC1 in pancreatic cancer cells triggers the molecular process of
      EMT, which translates to increased invasiveness and metastasis. EMT was
      significantly reduced when MUC1 was genetically deleted in a mouse model of PDA
      or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to
      phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting,
      we revealed a significant increase in vimentin, Slug and Snail expression with
      repression of E-Cadherin in MUC1-expressing cells compared with cells expressing
      the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed
      to co-immunoprecipitate with beta-catenin and translocate to the nucleus, thereby
      blocking transcription of the genes associated with EMT and metastasis. Thus,
      functional tyrosines are critical in stimulating the interactions between MUC1
      and beta-catenin and their nuclear translocation to initiate the process of EMT.
      This study signifies the oncogenic role of MUC1 CT and is the first to identify a
      direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may
      have implications in future design of MUC1-targeted therapies for pancreatic
      cancer.

PMID- 21102521
TI  - Differential recruitment of nuclear receptor coregulators in ligand-dependent
      transcriptional repression by estrogen receptor-alpha.
AB  - Estrogen receptors (ERs) are normally expressed in breast tissues and mediate
      hormonal functions during development and in female reproductive physiology. In
      the majority of breast cancers, ERs are involved in regulating tumor cell
      proliferation and serve as prognostic markers and therapeutic targets in the
      management of hormone-dependent tumors. At the molecular level, ERs function as
      ligand-dependent transcription factors and activate target-gene expression
      following hormone stimulation. Recent transcriptomic and whole-genome-binding
      studies suggest, however, that ligand-activated ERs can also repress the
      expression of a significant subset of target genes. To characterize the molecular
      mechanisms of transcriptional repression by ERs, we examined recruitment of
      nuclear receptor coregulators, histone modifications and RNA polymerase II
      docking at ER-binding sites and cis-regulatory regions adjacent to repressed
      target genes. Moreover, we utilized gene expression data from patient samples to
      determine potential roles of repressed target genes in breast cancer biology.
      Results from these studies indicate that nuclear receptor corepressor recruitment
      is a key feature of ligand-dependent transcriptional repression by Ers, and some
      repressed target genes are associated with disease progression and response to
      endocrine therapy. These findings provide preliminary insights into a novel
      aspect of the molecular mechanisms of ER functions and their potential roles in
      hormonal carcinogenesis and breast cancer biology.

PMID- 21102522
TI  - Diet and tumor LKB1 expression interact to determine sensitivity to anti
      neoplastic effects of metformin in vivo.
AB  - Hypothesis-generating epidemiological research has suggested that cancer burden
      is reduced in diabetics treated with metformin and experimental work has raised
      questions regarding the role of direct adenosine monophosphate-activated protein
      kinase (AMPK)-mediated anti-neoplastic effects of metformin as compared with
      indirect effects attributable to reductions in circulating insulin levels in the
      host. We treated both tumor LKB1 expression and host diet as variables, and
      observed that metformin inhibited tumor growth and reduced insulin receptor
      activation in tumors of mice with diet-induced hyperinsulinemia, independent of
      tumor LKB1 expression. In the absence of hyperinsulinemia, metformin inhibited
      only the growth of tumors transfected with short hairpin RNA against LKB1, a
      finding attributable neither to an effect on host insulin level nor to activation
      of AMPK within the tumor. Further investigation in vitro showed that cells with
      reduced LKB1 expression are more sensitive to metformin-induced adenosine
      triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent
      energy-conservation mechanisms. Thus, loss of function of LKB1 can accelerate
      proliferation in contexts where it functions as a tumor suppressor, but can also
      sensitize cells to metformin. These findings predict that any clinical utility of
      metformin or similar compounds in oncology will be restricted to subpopulations
      defined by host insulin levels and/or loss of function of LKB1.

PMID- 21102523
TI  - Transforming growth factor-beta regulates the sphere-initiating stem cell-like
      feature in breast cancer through miRNA-181 and ATM.
AB  - Recent studies indicate that a subset of cancer cells possessing stem cell
      properties, referred to as cancer-initiating or cancer stem cells (CSCs), have
      crucial roles in tumor initiation, metastasis and resistance to anticancer
      therapies. Transforming growth factor (TGF)-beta and their family members have
      been implicated in both normal (embryonic and somatic) stem cells and CSCs. In
      this study, we observed that exposure to TGF-beta increased the population of
      breast cancer (BC) cells that can form mammospheres in suspension, a feature
      endowed by stem cells. This was mediated by the micro (mi)RNA family miR-181,
      which was upregulated by TGF-beta at the post-transcriptional level. Levels of
      the miR-181 family members were elevated in mammospheres grown in
      undifferentiating conditions, compared with cells grown in two-dimensional
      conditions. Ataxia telangiectasia mutated (ATM), a target gene of miR-181,
      exhibited reduced expression in mammospheres and upon TGF-beta treatment.
      Overexpression of miR-181a/b, or depletion of ATM or its substrate CHK2, was
      sufficient to induce sphere formation in BC cells. Finally, knockdown of ATM
      enhanced in vivo tumorigenesis of the MDA361 BC cells. Our results elucidate a
      novel mechanism through which the TGF-beta pathway regulates the CSC property by
      interfering with the tumor suppressor ATM, providing insights into the cellular
      and environmental factors regulating CSCs, which may guide future studies on
      therapeutic strategies targeting these cells.

PMID- 21102524
TI  - RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP
      translation.
AB  - Expression of the intrinsic cellular caspase inhibitor XIAP is regulated
      primarily at the level of protein synthesis. The 5' untranslated region harbours
      an Internal Ribosome Entry Site (IRES) motif that supports cap-independent
      translation of XIAP mRNA during conditions of cellular stress. In this study, we
      show that the RNA-binding protein HuR, which is known to orchestrate an
      antiapoptotic cellular program, stimulates translation of XIAP mRNA through XIAP
      IRES. We further show that HuR binds to XIAP IRES in vitro and in vivo, and
      stimulates recruitment of the XIAP mRNA into polysomes. Importantly, protection
      from the apoptosis-inducing agent etoposide by overexpression of HuR requires the
      presence of XIAP, suggesting that HuR-mediated cytoprotection is partially
      executed through enhanced XIAP translation. Our data suggest that XIAP belongs to
      the HuR-regulated RNA operon of antiapoptotic genes, which, along with Bcl-2, Mcl
      1 and ProTalpha, contributes to the regulation of cell survival.

PMID- 21102525
TI  - Oncogenic kinase NPM/ALK induces expression of HIF1alpha mRNA.
AB  - The mechanisms of malignant cell transformation mediated by the oncogenic
      anaplastic lymphoma kinase (ALK) tyrosine kinase remain only partially
      understood. In this study, we report that T-cell lymphoma (TCL) cells carrying
      the nucleophosmin (NPM)/ALK fusion protein (ALK+ TCL) strongly express hypoxia
      induced factor 1alpha (HIF1alpha) mRNA, even under normoxic conditions, and
      markedly upregulate HIF1alpha protein expression under hypoxia. HIF1alpha
      expression is strictly dependent on the expression and enzymatic activity of
      NPM/ALK, as shown in BaF3 cells transfected with wild-type NPM/ALK and kinase
      inactive NPM/ALK K210R mutant and by the inhibition of the NPM/ALK function in
      ALK+ TCL cells by a small-molecule ALK inhibitor. NPM/ALK induces HIF1alpha
      expression by upregulating its gene transcription through its key signal
      transmitter signal transducer and activator of transcription 3 (STAT3), which
      binds to the HIF1alpha gene promoter as shown by the chromatin
      immunoprecipitation assay and is required for HIF1alpha gene expression as
      demonstrated by its small interfering RNA-mediated depletion. In turn, depletion
      of HIF1alpha increases mammalian target of rapamycin complex 1 activation, cell
      growth and proliferation and decreases vascular endothelial growth factor
      synthesis. These results identify a novel cell-transforming property of NPM/ALK,
      namely its ability to induce the expression of HIF1alpha, a protein with an
      important role in carcinogenesis. These results also provide another rationale to
      therapeutically target NPM/ALK and STAT3 in ALK+ TCL.

PMID- 21102526
TI  - Ribosomal protein S6 is highly expressed in non-Hodgkin lymphoma and associates
      with mRNA containing a 5' terminal oligopyrimidine tract.
AB  - The molecular mechanism(s) linking tumorigenesis and morphological alterations in
      the nucleolus are presently coming into focus. The nucleolus is the cellular
      organelle in which the formation of ribosomal subunits occurs. Ribosomal
      biogenesis occurs through the transcription of ribosomal RNA (rRNA), rRNA
      processing and production of ribosomal proteins. An error in any of these
      processes may lead to deregulated cellular translation, evident in multiple
      cancers and 'ribosomopathies'. Deregulated protein synthesis may be achieved
      through the overexpression of ribosomal proteins as seen in primary leukemic
      blasts with elevated levels of ribosomal proteins S11 and S14. In this study, we
      demonstrate that ribosomal protein S6 (RPS6) is highly expressed in primary
      diffuse large B-cell lymphoma (DLBCL) samples. Genetic modulation of RPS6 protein
      levels with specifically targeted short hairpin RNA (shRNA) lentiviruses led to a
      decrease in the actively proliferating population of cells compared with control
      shRNA. Low-dose rapamycin treatments have been shown to affect the translation of
      5' terminal oligopyrimidine (5' TOP) tract mRNA, which encodes the translational
      machinery, implicating RPS6 in 5' TOP translation. Recently, it was shown that
      disruption of 40S ribosomal biogenesis through specific small inhibitory RNA
      knockdown of RPS6 defined RPS6 as a critical regulator of 5' TOP translation. For
      the first time, we show that RPS6 associates with multiple mRNAs containing a 5'
      TOP tract. These findings expand our understanding of the mechanism(s) involved
      in ribosomal biogenesis and deregulated protein synthesis in DLBCL.

PMID- 21102528
TI  - One size does not fit all for transcriptomes.

PMID- 21102529
TI  - Statistical interaction in human genetics: how should we model it if we are
      looking for biological interaction?

PMID- 21102530
TI  - Medical oncology: Chemoradiotherapy for NSCLC-does a 'standard' exist?

PMID- 21102527
TI  - Synonymous but not the same: the causes and consequences of codon bias.
AB  - Despite their name, synonymous mutations have significant consequences for
      cellular processes in all taxa. As a result, an understanding of codon bias is
      central to fields as diverse as molecular evolution and biotechnology. Although
      recent advances in sequencing and synthetic biology have helped to resolve
      longstanding questions about codon bias, they have also uncovered striking
      patterns that suggest new hypotheses about protein synthesis. Ongoing work to
      quantify the dynamics of initiation and elongation is as important for
      understanding natural synonymous variation as it is for designing transgenes in
      applied contexts.

PMID- 21102531
TI  - Pediatric oncology: G-CSF counteracts chemotherapy toxicity in neuroblastoma.

PMID- 21102532
TI  - Pancreatic cancer: understanding and overcoming chemoresistance.
AB  - Pancreatic cancer is a highly aggressive malignancy. This feature is believed to
      be partly attributable to the chemotherapy-resistant characteristics of specific
      subgroups of pancreatic cancer cells, namely those with an epithelial-mesenchymal
      transition (EMT) phenotype and cancer stem cells. Accumulating evidence suggests
      that several new and emerging concepts might be important in the drug-resistant
      phenotype of these cell types. An understanding of the molecular mechanisms
      underlying drug resistance in patients with pancreatic cancer might help
      researchers to devise novel strategies to overcome such resistance. In
      particular, microRNAs (miRNAs) seem to be critical regulators of drug resistance
      in pancreatic cancer cells. Selective and targeted elimination of cells with an
      EMT phenotype and cancer stem cells could be achieved by regulating the
      expression of specific miRNAs.

PMID- 21102533
TI  - Insights into epiploic appendagitis.
AB  - Epiploic appendagitis is a rare cause of abdominal pain. Diagnosis of epiploic
      appendagitis, although infrequent, is easily made with CT or ultrasonography in
      experienced hands. As reported in the literature, most patients with primary
      epiploic appendagitis are treated conservatively without surgery, with or without
      anti-inflammatory drugs. A small number of patients are treated with antibiotics
      and some patients require surgical intervention to ensure therapeutic success.
      Symptoms of primary epiploic appendagitis usually resolve with or without
      treatment within a few days. A correct diagnosis of epiploic appendagitis with
      imaging procedures enables conservative and successful outpatient management of
      the condition and avoids unnecessary surgical intervention and associated
      additional health-care costs. Gastroenterologists and all medical personnel
      should be aware of this rare disease, which mimics many other intra-abdominal
      acute and subacute conditions, such as diverticulitis, cholecystitis and
      appendicitis. This article reviews epiploic appendagitis and includes discussion
      of clinical findings, pathophysiology, diagnosis and therapeutic possibilities.

PMID- 21102534
TI  - A multimeric immunogen for the induction of immune memory to beta-amyloid.
AB  - The development of active immunotherapy for Alzheimer's disease (AD) requires the
      identification of immunogens that can ensure a high titer antibody response
      toward beta-amyloid, whereas minimizing the risks of a cell-mediated adverse
      reaction. We describe here two novel anti-beta-amyloid vaccines that consist of
      'virus like particles' formed by a domain of the bacterial protein E2 that is
      able to self-assemble into a 60-mer peptide. Peptides 1-11 and 2-6 of beta
      amyloid were displayed as N terminal fusions on the surface of the E2 particles.
      E2-based vaccines induced a fast-rising, robust and persistent antibody response
      to beta-amyloid in all vaccinated mice. The immune memory induced by a single
      administration of vaccine (1-11) E2 can be rapidly mobilized by a single booster
      injection, leading to a very high serum concentration of anti-beta-amyloid
      antibodies (above 1 mg ml(-1)). E2 vaccination polarizes the immune response
      toward the production of the anti-inflammatory cytokine interleukin-4 and does
      not induce a T cell response to beta-amyloid. Thus, E2-based vaccines are
      promising candidates for the development of immunotherapy protocols for AD.

PMID- 21102535
TI  - Toward a functional characterization of blood monocytes.

PMID- 21102536
TI  - The canonical BMP signaling pathway is involved in human monocyte-derived
      dendritic cell maturation.
AB  - Bone morphogenetic proteins (BMPs), members of the transforming growth factor
      beta superfamily, are multifunctional polypeptides regulating a broad spectrum of
      functions in embryonic and adult tissues. Recent reports have demonstrated that
      BMPs regulate the survival, proliferation and differentiation of several cell
      types in the immune system. In this study, we investigate the effects of BMP
      signaling activation on the capacity of human dendritic cells (DCs) to stimulate
      immune responses. Human DCs express type I and type II BMP receptors (BMPRIA,
      BMPRIB, type IA activin receptor, BMPRII) and BMP signal transduction molecules
      (Smad1, 5, and 8, as well as Smad4). On BMP stimulation, Id1-3 (inhibitor of
      differentiation 1-3/DNA binding) mRNA expression is upregulated and this effect
      can be blocked with the inhibitor dorsomorphin, showing that the canonical BMP
      signal transduction pathway is functionally active in DCs. BMP signaling
      activation promotes the phenotypic maturation of human DCs by increasing the
      expression of co-stimulatory molecules and also CD83, programmed cell death
      ligand 1 (PD-L1) and PD-L2, and stimulates cytokine secretion, mainly interleukin
      8 and tumor necrosis factor-alpha. Accordingly, BMP-treated DCs exhibit an
      enhanced T-cell stimulatory capacity. BMP signaling also enhances the survival of
      human DCs increasing the Bcl-2/Bax ratio. Finally, the expression of Runx
      transcription factors is increased in mature DCs, and the mRNA levels of Runx1-3
      are upregulated in response to BMP stimulation, indicating that Runx
      transcription factor family may mediate the effects of BMP signaling in human DC
      maturation.

PMID- 21102537
TI  - Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal
      epithelium.
AB  - The innate immune system is present throughout the female reproductive tract and
      functions in synchrony with the adaptive immune system to provide protection in a
      way that enhances the chances for fetal survival, while protecting against
      potential pathogens. Recent data show that activation of Toll-like receptor
      (TLR)2 and 4 by low-molecular weight hyaluronic acid (LMW-HA) in the epidermis
      induces secretion of the antimicrobial peptide beta-defensin 2. In the present
      work, we show that LMW-HA induces vaginal epithelial cells to release different
      antimicrobial peptides, via activation of TLR2 and TLR4. Further, we found that
      LMW-HA favors repair of vaginal epithelial injury, involving TLR2 and TLR4, and
      independently from its classical receptor CD44. This wound-healing activity of
      LMW-HA is dependent from an Akt/phosphatidylinositol 3 kinase pathway. Therefore,
      these findings suggest that the vaginal epithelium is more than a simple physical
      barrier to protect against invading pathogens: on the contrary, this surface acts
      as efficient player of innate host defense, which may modulate its antimicrobial
      properties and injury restitution activity, following LMW-HA stimulation; this
      activity may furnish an additional protective activity to this body compartment,
      highly and constantly exposed to microbiota, ameliorating the self-defense of the
      vaginal epithelium in both basal and pathological conditions.

PMID- 21102538
TI  - Recognition of cellular implants by the brain's innate immune system.
AB  - Currently, much attention is given to the development of cellular therapies for
      treatment of central nervous system (CNS) injuries. Diverse cell implantation
      strategies, either to directly replace damaged neural tissue or to create a
      neuroregenerative environment, are proposed to restore impaired brain function.
      However, because of the complexity of the CNS, it is now becoming clear that the
      contribution of cell implantation into the brain will mainly act in a supportive
      manner. In addition, given the time dependence of neural development during
      embryonic and post-natal life, cellular implants, either self or non-self, will
      most likely have to interact for a sustained period of time with both healthy and
      injured neural tissue. The latter also implies potential recognition of cellular
      implants by the innate immune system of the brain. In this review, we will
      emphasize on preclinical observations in rodents, regarding the recognition and
      immunogenicity of autologous, allogeneic and xenogeneic cellular implants in the
      CNS of immune-competent hosts. Taken together, we here suggest that a profound
      study of the interaction between cellular grafts and the brain's innate immune
      system will be inevitable before clinical cell transplantation in the CNS can be
      performed successfully.

PMID- 21102539
TI  - SLAM (CD150) is a multitasking immunoreceptor: from cosignalling to bacterial
      recognition.

PMID- 21102541
TI  - A case of primary aldosteronism revealed after renal transplantation.
AB  - BACKGROUND: A 57-year-old woman was referred to a nephrology clinic because of
      chronic hypokalemia. She had a history of polycystic kidney disease, resistant
      hypertension, atrial fibrillation, type 2 diabetes, stroke, and end-stage renal
      disease, and had received a kidney transplant from a deceased donor at the age of
      48 years. At presentation, the patient described symptoms of chronic fatigue and
      muscle aches, but she did not report pareses. Her medications included four
      antihypertensive agents, glucose-lowering drugs, immunosuppressants, digoxin, a
      coumarin derivative, and potassium chloride. INVESTIGATIONS: Full history,
      physical examination, laboratory testing of blood and urine, including
      aldosterone-torenin ratio, and a saline infusion test. DIAGNOSIS: Primary
      aldosteronism. MANAGEMENT: Treatment with spironolactone resulted in prompt
      control of hypertension and hypokalemia, allowing discontinuation of potassium
      chloride and reduction in antihypertensive medication.

PMID- 21102540
TI  - Atherosclerosis in chronic kidney disease: the role of macrophages.
AB  - Patients with chronic kidney disease (CKD) are at increased risk of
      atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates
      atherosclerosis in animal models. Macrophages are central to atherogenesis
      because they regulate cholesterol traffic and inflammation in the arterial wall.
      CKD influences macrophage behavior at multiple levels, rendering them
      proatherogenic. Even at normal creatinine levels, macrophages from
      uninephrectomized Apoe(-/-) mice are enriched in cholesterol owing to
      downregulation of cholesterol transporter ATP-binding cassette subfamily A member
      1 levels and activation of nuclear factor kappaB, which leads to impaired
      cholesterol efflux. Interestingly, treatment with an angiotensin-II-receptor
      blocker (ARB) improves these effects. Moreover, atherosclerotic aortas from Apoe(
      /-) mice transplanted into renal-ablated normocholesterolemic recipients show
      plaque progression and increased macrophage content instead of the substantial
      regression seen in recipient mice with intact kidneys. ARBs reduce
      atherosclerosis development in mice with partial renal ablation. These results,
      combined with the clinical benefits of angiotensin-converting-enzyme (ACE)
      inhibitors and ARBs in patients with CKD, suggest an important role for the
      angiotensin system in the enhanced susceptibility to atherosclerosis seen across
      the spectrum of CKD. The role of macrophages could explain why these therapies
      may be effective in end-stage renal disease, one of the few conditions in which
      statins show no clinical benefit.

PMID- 21102542
TI  - New insights into postrenal transplant hemolytic uremic syndrome.
AB  - After renal transplantation, hemolytic uremic syndrome (HUS) may occur either as
      a recurrent or de novo form. Over the past decade, much effort has been devoted
      to elucidating the pathogenesis of atypical HUS (aHUS). Approximately 60-70%
      patients with aHUS have mutations in regulatory factors of the complement system
      or antibodies against complement factor H. The risk of post-transplant recurrence
      of aHUS depends on the genetic abnormality involved, and ranges from 15% to 20%
      in patients with mutations in the gene that encodes membrane cofactor protein and
      from 50% to 100% in patients with mutations in the genes that encode circulating
      regulators of complement. Given the poor outcomes associated with recurrence,
      isolated renal transplantation had been contraindicated in patients at high risk
      of aHUS recurrence. However, emerging therapies, including pre-emptive plasma
      therapy and anti-C5 component monoclonal antibody (eculizumab) treatment have
      provided promising results and should further limit indications for the risky
      procedure of combined liver-kidney transplantation. Studies from the past 2 years
      have demonstrated genetic abnormalities in complement regulators in 30% of renal
      transplant recipients who experienced de novo HUS after renal transplantation.
      This finding suggests that the burden of endothelial injury in a post
      transplantation setting may trigger de novo HUS in the presence of mild genetic
      susceptibility to HUS.

PMID- 21102545
TI  - Therapy: The second time as farce: rosiglitazone and the regulators.
AB  - Rosiglitazone is the second of the marketed thiazolidinediones to fall from
      grace, and its demise bears an uncanny resemblance to the earlier downfall of
      troglitazone. Both narratives demonstrate the inadequacy of a regulatory system
      that is mandated to place a higher value on commercial secrecy than on patient
      safety.

PMID- 21102544
TI  - The role of AIRE in human autoimmune disease.
AB  - The autoimmune regulator (AIRE) gene encodes a transcription factor involved in
      the presentation of tissue-restricted antigens during T-cell development in the
      thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome
      (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy (APECED) syndrome, which is characterized by the clinical presentation
      of at least two of a triad of underlying disorders: Addison disease,
      hypoparathyroidism and chronic mucocutaneous candidiasis. This Review describes
      the process of positive and negative selection of developing T cells in the
      thymus and the role of AIRE as a regulator of peripheral antigen presentation.
      Furthermore, it addresses how mutations of this gene lead to the failure to
      eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes.

PMID- 21102543
TI  - Pathophysiology of articular chondrocalcinosis--role of ANKH.
AB  - Calcium pyrophosphate (CPP) crystal deposition (CPPD) is associated with ageing
      and osteoarthritis, and with uncommon disorders such as hyperparathyroidism,
      hypomagnesemia, hemochromatosis and hypophosphatasia. Elevated levels of synovial
      fluid pyrophosphate promote CPP crystal formation. This extracellular
      pyrophosphate originates either from the breakdown of nucleotide triphosphates by
      plasma-cell membrane glycoprotein 1 (PC-1) or from pyrophosphate transport by the
      transmembrane protein progressive ankylosis protein homolog (ANK). Although the
      etiology of apparent sporadic CPPD is not well-established, mutations in the ANK
      human gene (ANKH) have been shown to cause familial CPPD. In this Review, the key
      regulators of pyrophosphate metabolism and factors that lead to high
      extracellular pyrophosphate levels are described. Particular emphasis is placed
      on the mechanisms by which mutations in ANKH cause CPPD and the clinical
      phenotype of these mutations is discussed. Cartilage factors predisposing to CPPD
      and CPP-crystal-induced inflammation and current treatment options for the
      management of CPPD are also described.

PMID- 21102546
TI  - A patient with diabetes insipidus, anterior hypopituitarism and pituitary stalk
      thickening.
AB  - BACKGROUND: A 42-year-old woman presented to the neuroendocrine unit of a
      hospital with recent-onset polydipsia, polyuria and oligomenorrhea. She had no
      visual symptoms, head injury or history of malignancy. INVESTIGATIONS:
      Measurement of serum sodium and osmolality (as well as urine osmolality) after
      water deprivation, both before and after desmopressin administration. Measurement
      of basal serum concentrations of pituitary hormones, insulin-like growth factor 1
      and thyroid hormone, cosyntropin stimulation testing of adrenal function, and
      growth-hormone-releasing hormone-arginine stimulation testing. MRI of the
      pituitary, CT of the chest and abdomen, skeletal surveys, analyses of
      cerebrospinal fluid, serology and histologic examination of an excised, painful
      submandibular salivary gland. DIAGNOSIS: Central diabetes insipidus and anterior
      hypopituitarism secondary to Langerhans cell histiocytosis. MANAGEMENT:
      Replacement therapies, including desmopressin, levothyroxine, cyclic estrogen
      with medroxyprogesterone, and growth hormone. The stalk lesion remained stable
      after 7 years without specific therapy.

PMID- 21102547
TI  - Transcription alterations of members of the ubiquitin-proteasome network in
      prostate carcinoma.
AB  - The purpose of this work was to investigate the role of the ubiquitin-proteasome
      network (UPN) in prostate cancer (PCA) and to elicit potential markers for this
      disease. The UPN represents a key factor in the maintenance of cellular
      homoeostasis as a result of its fundamental function in the regulation of
      intracellular protein degradation. Members of this network have a role in the
      biology of haematological and solid tumours. Tumour cells and normal epithelial
      cells from 22 prostatectomy specimens were isolated by laser microdissection.
      Prostate biopsy samples from healthy individuals served for technical calibration
      and as controls. Transcript levels of eight selected genes with E3 ubiquitin
      ligase activity (labelling target proteins for proteasome degradation) and two
      genes belonging to the proteasome-multienzyme complex itself were analysed by
      quantitative real-time RT-PCR. The proteasome genes PSMC4 and PSMB5 and the E3
      ubiquitin ligase NEDD4L were significantly and coherently upregulated in PCA
      cells compared with the corresponding adjacent normal prostate tissue.
      Transcription of the E3 ubiquitin ligase SMURF2 was significantly higher in organ
      confined tumours (pT2) compared with non-organ-confined cancers (pT3). The
      results indicate a role for PSMC4 and PSMB5 and the E3 ubiquitin ligase NEDD4L in
      prostate tumourigenesis, whereas SMURF2 downregulation could be associated with
      clinical progression. NEDD4L and SMURF2 both target transforming growth factor
      (TGF)-beta for degradation. This reflects the pleiotropic role of the TGF-beta
      signalling pathway acting as a tumour suppressor in normal and pre-cancerous
      cells, but having oncogenic properties in progressing cancer. Further studies
      have to elucidate whether these alterations could represent clinically relevant
      PCA-diagnostic and progression markers.

PMID- 21102548
TI  - SUMO wrestling in cell movement.

PMID- 21102549
TI  - Direct differentiation of atrial and ventricular myocytes from human embryonic
      stem cells by alternating retinoid signals.
AB  - Although myocyte cell transplantation studies have suggested a promising
      therapeutic potential for myocardial infarction, a major obstacle to the
      development of clinical therapies for myocardial repair is the difficulties
      associated with obtaining relatively homogeneous ventricular myocytes for
      transplantation. Human embryonic stem cells (hESCs) are a promising source of
      cardiomyocytes. Here we report that retinoid signaling regulates the fate
      specification of atrial versus ventricular myocytes during cardiac
      differentiation of hESCs. We found that both Noggin and the pan-retinoic acid
      receptor antagonist BMS-189453 (RAi) significantly increased the cardiac
      differentiation efficiency of hESCs. To investigate retinoid functions, we
      compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results
      showed that the expression levels of the ventricular-specific gene IRX-4 were
      radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular
      specific marker, was expressed in the majority of the cardiomyocytes in
      Noggin+RAi-treated cultures, but not in the cardiomyocytes of Noggin+RA-treated
      cultures. Flow cytometry analysis and electrophysiological studies indicated that
      with 64.7 +/- 0.88% (mean +/-s.e.m) cardiac differentiation efficiency, 83% of
      the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like
      action potentials (APs). With 50.7 +/- 1.76% cardiac differentiation efficiency,
      94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like
      APs. These results were further confirmed by imaging studies that assessed the
      patterns and properties of the Ca(2+) sparks of the cardiomyocytes from the two
      cultures. These findings demonstrate that retinoid signaling specifies the atrial
      versus ventricular differentiation of hESCs. This study also shows that
      relatively homogeneous embryonic atrial- and ventricular-like myocyte populations
      can be efficiently derived from hESCs by specifically regulating Noggin and
      retinoid signals.

PMID- 21102552
TI  - Acute, short-term hyperinsulinemia increases olfactory threshold in healthy
      subjects.
AB  - OBJECTIVE: Smell plays an important role in feeding behavior. We therefore tested
      whether insulin as a postprandial signal is involved in the regulation of
      olfactory function. RESEARCH DESIGN AND METHODS: We assessed olfactory thresholds
      in eight lean subjects (age: 34 +/- 7 years, M/F: 5/3) before and during a 2-h
      hyperinsulinemic (1 mU kg(-1) min(-1)) euglycemic clamp and in eight lean fasted
      subjects (age: 36 +/- 6 years, M/F: 5/3) without insulin infusion at the same
      time of the day. To define odor thresholds, standardized 'sniffing sticks' were
      used. RESULTS: Odor thresholds decreased from 7.8 +/- 1.2 to 6.2 +/- 1.1 during
      euglycemic hyperinsulinemia (P=0.0173), representing an increase in odor
      threshold. In the control group, odor thresholds were 8.3 +/- 1.6 and did not
      change after 120 min of fasting (8.9 +/- 2.2, P=0.6). CONCLUSIONS: Increased
      insulin levels lead to a reduced smelling capacity, potentially reducing the
      pleasantness of eating. Therefore, insulin action in the olfactory bulb may be
      involved in the process of satiation and may thus be of interest in the
      pathogenesis of obesity.

PMID- 21102551
TI  - Analysis of FTO gene variants with obesity and glucose homeostasis measures in
      the multiethnic Insulin Resistance Atherosclerosis Study cohort.
AB  - OBJECTIVE: Previous studies have replicated the association of variants within
      FTO (fat mass- and obesity-associated) intron 1 with obesity and adiposity
      quantitative traits in populations of European ancestry. Non-European
      populations, however, have not been so intensively studied. The goal of this
      investigation was to examine the association of FTO single-nucleotide
      polymorphisms (SNPs), prominent in the literature in a multiethnic sample of non
      Hispanic White American (n=458), Hispanic American (n=373) and African American
      (n=288) subjects from the Insulin Resistance Atherosclerosis Study (IRAS). This
      cohort provides the unique ability to evaluate how variation within FTO
      influences measures of adiposity and glucose homeostasis in three different
      ethnicities, which were ascertained and examined using a common protocol. DESIGN:
      A total of 26 FTO SNPs were genotyped, including those consistently associated in
      the literature (rs9939609, rs8050136, rs1121980, rs1421085, rs17817449 and
      rs3751812), and tested for association with adiposity and glucose homeostasis
      traits. RESULTS: For the adiposity phenotypes, these and other SNPs were
      associated with body mass index (BMI) in both non-Hispanic Whites (P-values
      ranging from 0.015 to 0.048) and Hispanic Americans (P-values ranging from 7.1 *
      10(-6) to 0.027). In Hispanic Americans, four other SNPs (rs8047395, rs10852521,
      rs8057044 and rs8044769) still showed evidence of association after multiple
      comparisons adjustment (P-values ranging from 5.0 * 10(-5) to 5.2 * 10(-4)). The
      historically associated BMI SNPs were not associated in the African Americans,
      but rs1108102 was associated with BMI (P-value of 5.4 * 10(-4)) after accounting
      for multiple comparisons. For glucose homeostasis traits, associations were seen
      with acute insulin response in non-Hispanic Whites and African Americans.
      However, all associations with glucose homeostasis measures were no longer
      significant after adjusting for multiple comparisons. CONCLUSION: These results
      replicate the association of FTO intron 1 variants with BMI in non-Hispanic
      Whites and Hispanic Americans but show little evidence of association in African
      Americans, suggesting that the effect of FTO variants on adiposity phenotypes
      shows genetic heterogeneity dependent on ethnicity.

PMID- 21102550
TI  - A single NFkappaB system for both canonical and non-canonical signaling.
AB  - Two distinct nuclear factor kappaB (NFkappaB) signaling pathways have been
      described; the canonical pathway that mediates inflammatory responses, and the
      non-canonical pathway that is involved in immune cell differentiation and
      maturation and secondary lymphoid organogenesis. The former is dependent on the
      IkappaB kinase adaptor molecule NEMO, the latter is independent of it. Here, we
      review the molecular mechanisms of regulation in each signaling axis and attempt
      to relate the apparent regulatory logic to the physiological function. Further,
      we review the recent evidence for extensive cross-regulation between these two
      signaling axes and summarize them in a wiring diagram. These observations suggest
      that NEMO-dependent and -independent signaling should be viewed within the
      context of a single NFkappaB signaling system, which mediates signaling from both
      inflammatory and organogenic stimuli in an integrated manner. As in other
      regulatory biological systems, a systems approach including mathematical models
      that include quantitative and kinetic information will be necessary to
      characterize the network properties that mediate physiological function, and that
      may break down to cause or contribute to pathology.

PMID- 21102553
TI  - Measurement of longitudinal changes in body composition during weight loss and
      maintenance in overweight and obese subjects using air-displacement
      plethysmography in comparison with the deuterium dilution technique.
AB  - BACKGROUND: Air-displacement plethysmography (ADP) may be a valid and practical
      technique to assess body composition in a clinical setting. OBJECTIVE: This study
      aimed to assess longitudinal changes in body composition using ADP and to compare
      it with the deuterium dilution technique. DESIGN: The study was a 6-months
      dietary intervention, consisting of four phases. The first month, subjects were
      fed in energy balance (phase I). This was followed by 1 month with an energy
      intake of 33% of energy requirements (phase II), followed by 2 months at 67% of
      energy requirements (phase III) and 2 months of ad libitum intake (phase IV).
      Body composition was assessed using ADP (Bod Pod) and deuterium dilution at
      baseline and at the end of each phase. The baseline analysis included 111
      subjects (88 female). Sixty-one subjects (50 female) completed all measurements
      and were included in the longitudinal analysis. RESULTS: At baseline, the fat
      mass (FM) as assessed with the Bod Pod was on average 2.3 +/- 4.2 kg (mean +/- 2
      s.d.) higher than that assessed with deuterium dilution. The difference in FM
      between techniques increased significantly with increasing FM (R(2)=0.23;
      P<0.001). Both techniques showed significant changes in FM over time P<0.001). On
      average, FM as assessed with the Bod Pod was 2.0 kg higher than with deuterium
      dilution (P<0.001). During phase II, there was a significant interaction between
      time and method, meaning that the Bod Pod showed a larger decrease in FM than
      deuterium dilution. CONCLUSIONS: The Bod Pod was able to detect all changes in
      the body composition, but consistently measured a higher FM than deuterium
      dilution.

PMID- 21102554
TI  - Association between obesity and reduced body temperature in dogs.
AB  - BACKGROUND: Industrialized nations are currently experiencing an obesity
      epidemic, the causes of which are not fully known. One possible mechanism of
      enhanced energy efficiency that has received almost no attention is a reduction
      in the metabolic cost of homeothermy, which could be achieved by a modest
      lowering of body core temperature. We evaluated the potential of this obesity
      inducing mechanism in a canine model of the metabolic syndrome. METHODS: We
      compared the rectal temperature of lean dogs and obese dogs by (a) conducting
      cross-sectional measurements in 287 dogs of many breeds varying greatly in body
      size, (b) conducting longitudinal measurements in individual dogs over 7-10 years
      and (c) tracking rectal temperature of lean and obese dogs at 3-h intervals for
      48 consecutive hours in the laboratory. RESULTS: We found that larger dogs have
      lower rectal temperatures than smaller dogs and that, for the same body mass,
      obese dogs have lower rectal temperatures than lean dogs. The results were
      consistent in the cross-sectional, longitudinal and around-the-clock
      measurements. CONCLUSION: These findings document an association between obesity
      and reduced body temperature in dogs and support the hypothesis that obesity in
      this and other species of homeotherms may result from an increase in metabolic
      efficiency achieved by a regulated lowering of body temperature.

PMID- 21102555
TI  - RsgA releases RbfA from 30S ribosome during a late stage of ribosome
      biosynthesis.
AB  - RsgA is a 30S ribosomal subunit-binding GTPase with an unknown function, shortage
      of which impairs maturation of the 30S subunit. We identified multiple gain-of
      function mutants of Escherichia coli rbfA, the gene for a ribosome-binding
      factor, that suppress defects in growth and maturation of the 30S subunit of an
      rsgA-null strain. These mutations promote spontaneous release of RbfA from the
      30S subunit, indicating that cellular disorders upon depletion of RsgA are due to
      prolonged retention of RbfA on the 30S subunit. We also found that RsgA enhances
      release of RbfA from the mature 30S subunit in a GTP-dependent manner but not
      from a precursor form of the 30S subunit. These findings indicate that the
      function of RsgA is to release RbfA from the 30S subunit during a late stage of
      ribosome biosynthesis. This is the first example of the action of a GTPase on the
      bacterial ribosome assembly described at the molecular level.

PMID- 21102556
TI  - RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.
AB  - The evolutionarily conserved Notch signal transduction pathway regulates
      fundamental cellular processes during embryonic development and in the adult.
      Ligand binding induces presenilin-dependent cleavage of the receptor and a
      subsequent nuclear translocation of the Notch intracellular domain (NICD). In the
      nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP
      J)/CBF-1 transcription factor to induce expression of Notch target genes. Here,
      we report the identification and functional characterization of RBP-J interacting
      and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting
      protein. RITA is a highly conserved 36 kDa protein that, most interestingly,
      binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and
      nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally,
      we show that RITA can reverse a Notch-induced loss of primary neurogenesis in
      Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated
      transcription. Thus, we propose that RITA acts as a negative modulator of the
      Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its
      amounts are limiting.

PMID- 21102557
TI  - Interaction of calmodulin with Sec61alpha limits Ca2+ leakage from the
      endoplasmic reticulum.
AB  - In eukaryotes, protein transport into the endoplasmic reticulum (ER) is
      facilitated by a protein-conducting channel, the Sec61 complex. The presence of
      large, water-filled pores with uncontrolled ion permeability, as formed by Sec61
      complexes in the ER membrane, would seriously interfere with the regulated
      release of calcium from the ER lumen into the cytosol, an essential mechanism for
      intracellular signalling. We identified a calmodulin (CaM)-binding motif in the
      cytosolic N-terminus of mammalian Sec61alpha that bound CaM but not Ca2+-free
      apocalmodulin with nanomolar affinity and sequence specificity. In single-channel
      measurements, CaM potently mediated Sec61-channel closure in Ca2+-dependent
      manner. At the cellular level, two different CaM antagonists stimulated calcium
      release from the ER through Sec61 channels. However, protein transport into
      microsomes was not modulated by Ca2+-CaM. Molecular modelling of the
      ribosome/Sec61/CaM complexes supports the view that simultaneous ribosome and CaM
      binding to the Sec61 complex may be possible. Overall, CaM is involved in
      limiting Ca2+ leakage from the ER.

PMID- 21102559
TI  - Anterograde axonal transport of AAV2-GDNF in rat basal ganglia.
AB  - We elucidated the effects of parkinsonian degeneration on trafficking of AAV2
      GDNF in the nigro-striatum (nigro-ST) of unilaterally 6-hydroxydopamine (6-OHDA)
      lesioned rats. Vector infused into striatum (ST) was transported to substantia
      nigra (SN), both pars compacta (SNc), and pars reticulata (SNr). In the lesioned
      hemisphere, glial cell line-derived neurotrophic factor (GDNF) immunoreactivity
      was only found in SNr consistent with elimination of SNc dopaminergic (DA)
      neurons by 6-OHDA. Further analysis showed that striatal delivery of AAV2-GDNF
      resulted in GDNF expression in globus pallidus (GP), entopeduncular nucleus
      (EPN), and subthalamic nucleus (STN) in both lesioned and unlesioned hemispheres.
      Injection of vector into SN, covering both SNc and SNr, resulted in striatal
      expression of GDNF in the unlesioned hemisphere but not in the lesioned
      hemisphere. No expression was seen in GP or EPN. We conclude that adeno
      associated virus serotype 2 (AAV2) is transported throughout the nigro-ST
      exclusively by anterograde transport. This transport phenomenon directs GDNF
      expression throughout the basal ganglia in regions that are adversely affected in
      Parkinson's disease (PD) in addition to SNc. Delivery of vector to SN, however,
      does not direct expression of GDNF in ST, EPN, or GP. On this basis, we believe
      that striatal delivery of AAV2-GDNF is the preferred course of action for trophic
      rescue of DA function.

PMID- 21102560
TI  - Chronic systemic therapy with low-dose morpholino oligomers ameliorates the
      pathology and normalizes locomotor behavior in mdx mice.
AB  - The administration of antisense oligonucleotides (AOs) to skip one or more exons
      in mutated forms of the DMD gene and so restore the reading frame of the
      transcript is one of the most promising approaches to treat Duchenne muscular
      dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and
      safety of long-term AO administration have not been conducted. Furthermore, it is
      essential to determine the minimal effective dose and frequency of
      administration. In this study, two different low doses (LDs) of
      phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23
      in the mdx dystrophic mouse were administered for up to 12 months. Mice treated
      for 50 weeks showed a substantial dose-related amelioration of the pathology,
      particularly in the diaphragm. Moreover, the generalized physical activity was
      profoundly enhanced compared to untreated mdx mice showing that widespread,
      albeit partial, dystrophin expression restores the normal activity in mdx mice.
      Our results show for the first time that a chronic long-term administration of
      LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe,
      significantly ameliorates the muscular dystrophic phenotype and improves the
      activity of dystrophin-deficient mice, thus encouraging the further clinical
      translation of this approach in humans.

PMID- 21102558
TI  - Kinetochore-microtubule interactions: steps towards bi-orientation.
AB  - Eukaryotic cells segregate their chromosomes accurately to opposite poles during
      mitosis, which is necessary for maintenance of their genetic integrity. This
      process mainly relies on the forces generated by kinetochore-microtubule (KT-MT)
      attachment. During prometaphase, the KT initially interacts with a single MT
      extending from a spindle pole and then moves towards a spindle pole.
      Subsequently, MTs from the other spindle pole also interact with the KT.
      Eventually, one sister KT becomes attached to MTs from one pole while the other
      sister to those from the other pole (sister KT bi-orientation). If sister KTs
      interact with MTs with aberrant orientation, this must be corrected to attain
      proper bi-orientation (error correction) before the anaphase is initiated. Here,
      I discuss how KTs initially interact with MTs and how this interaction develops
      into bi-orientation; both processes are fundamentally crucial for proper
      chromosome segregation in the subsequent anaphase.

PMID- 21102561
TI  - Efficient generation of hepatoblasts from human ES cells and iPS cells by
      transient overexpression of homeobox gene HEX.
AB  - Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have
      the potential to differentiate into all cell lineages, including hepatocytes, in
      vitro. Induced hepatocytes have a wide range of potential application in
      biomedical research, drug discovery, and the treatment of liver disease. However,
      the existing protocols for hepatic differentiation of PSCs are not very
      efficient. In this study, we developed an efficient method to induce
      hepatoblasts, which are progenitors of hepatocytes, from human ESCs and iPSCs by
      overexpression of the HEX gene, which is a homeotic gene and also essential for
      hepatic differentiation, using a HEX-expressing adenovirus (Ad) vector under
      serum/feeder cell-free chemically defined conditions. Ad-HEX-transduced cells
      expressed alpha-fetoprotein (AFP) at day 9 and then expressed albumin (ALB) at
      day 12. Furthermore, the Ad-HEX-transduced cells derived from human iPSCs also
      produced several cytochrome P450 (CYP) isozymes, and these P450 isozymes were
      capable of converting the substrates to metabolites and responding to the
      chemical stimulation. Our differentiation protocol using Ad vector-mediated
      transient HEX transduction under chemically defined conditions efficiently
      generates hepatoblasts from human ESCs and iPSCs. Thus, our methods would be
      useful for not only drug screening but also therapeutic applications.

PMID- 21102562
TI  - Microvesicle-mediated RNA molecule delivery system using monocytes/macrophages.
AB  - Microvesicles (MVs) and exosomes, which are shed from cells as a cell-to-cell
      communication tool, are possible vehicles for navigating RNA molecules to body
      tissues. It is considered that intravenous injection of such MVs or exosomes from
      patients would not cause severe not-self and toxic reactions. Previously, we
      found that macrophages take up liposome-entrapped RNA molecules, some of which
      remain undegraded in the cells. Here, we demonstrate that transfected RNA
      molecules in human monocytic leukemia THP-1 cells were shed from THP-1
      macrophages as contents in MVs during incubation in serum-free medium, which
      shedding was shown by biochemical analyses such as quantitative reverse
      transcription (qRT)-PCR, expression of TSG101 (a membrane-associated exosomal
      protein), and immunoelectron microscopic study. More chemically modified RNA
      molecules (miR-143BPs) entrapped by MVs (MV-miR-143BPs) were secreted from THP-1
      macrophages after miR-143BP transfection compared with the amount after
      transfection with nonmodified miR-143 transfection. Furthermore, we show that the
      THP-1 macrophages, which were transfected with the miR-143BP ex vivo, secreted MV
      miR-143BPs in xenografted nude mice after intravenous injection, because miR-143
      levels were significantly increased in the serum, tumor, and kidney of the host
      animals. These data suggest that some of the transfected miR-143BPs were secreted
      from THP-1 macrophages as MV-RNAs both in vitro and in vivo.

PMID- 21102563
TI  - Neuroprotection by gene therapy targeting mutant SOD1 in individual pools of
      motor neurons does not translate into therapeutic benefit in fALS mice.
AB  - A major challenge in neurological gene therapy is delivery of the transgene to
      sufficient cell numbers in an atraumatic manner. This is particularly difficult
      for motor neuron (MN) diseases that have cells located across the entire spinal
      cord, brain stem, and cortex. We have used the familial mouse model of
      amyotrophic lateral sclerosis (ALS) to examine the feasibility of body-wide
      intramuscular injections of adeno-associated virus serotype 6 (AAV6), a vector
      capable of axonal retrograde transport, to deliver therapeutic genetic
      information across the lower MN axis. Neonatal muscle delivery of AAV expressing
      small hairpin RNAs (shRNAs) against the toxic transgene in this model, human
      mutant superoxide dismutase 1 (mSOD1), led to significant mSOD1 knockdown in the
      muscle as well as innervating MNs. This knockdown conferred neuroprotection and
      halted muscle atrophy in individually targeted MN pools. However, despite the
      vector being targeted to MNs that innervate muscle groups controlling eating,
      breathing, and locomotion, this approach was unable to therapeutically impact on
      disease progression in the ALS mouse model. These results stress the complexity
      of gene delivery for mSOD1 silencing and suggest that critical thresholds of
      protein knockdown and transduction across various cell types are required to
      translate local neuroprotective effects into functional improvements.

PMID- 21102564
TI  - A critical look at connectomics.
AB  - There is a public perception that connectomics will translate directly into
      insights for disease. It is essential that scientists and funding institutions
      avoid misrepresentation and accurately communicate the scope of their work.

PMID- 21102565
TI  - The eye on the needle.

PMID- 21102566
TI  - How hard is the CNS hardware?

PMID- 21102567
TI  - Anandamide serves two masters in the brain.

PMID- 21102568
TI  - Illuminating the locus coeruleus: control of posture and arousal.

PMID- 21102569
TI  - Intraprocedural tissue diagnosis during ERCP employing a new cytology preparation
      of forceps biopsy (Smash protocol).
AB  - OBJECTIVES: Techniques of tissue sampling at endoscopic retrograde
      cholangiopancreatography (ERCP) have been underutilized due to technical demands,
      low yield, and lack of immediate intraprocedural diagnosis. The objective of this
      study was to describe a new inexpensive, highly efficient ERCP tissue processing,
      and interpretation technique to address these issues. METHODS: A retrospective,
      institutional review board approved, single-center study was done at a tertiary
      care medical center. Between June 2004 and February 2009, 133 patients (age 38-95
      years; men 53%) with suspicious biliary strictures underwent ERCP with tissue
      sampling using a new technique. Small forceps biopsy specimens were forcefully
      smashed between two dry glass slides, immediately fixed, stained with rapid
      Papanicolaou, and interpreted by an on-site pathologist during the procedure
      (Smash protocol). RESULTS: Of the 117 proven to have cancer, true-positive Smash
      preps included pancreatic cancer 49/66 (74%), cholangiocarcinoma 23/29 (79%),
      metastatic cancer 8/15 (53%), and other 4/7 (57%). The median number of Smash
      biopsies to diagnosis was 3 (range 1-17). Suspicious or atypical results were
      considered to be negative in this study. There were no false positives and no
      complications. Smash had an overall sensitivity of 89/117 (76%) for all cases.
      The true-positive yield of immediate Smash prep cytology, combined with ERCP fine
      needle aspirate (FNA) and forceps biopsy histology was 77/95 (81%) for primary
      pancreaticobiliary cancers. CONCLUSIONS: Immediate cytopathologic diagnosis at
      ERCP was established in 72% of patients presenting with suspected malignant
      biliary obstruction using a new cytological preparation of forceps biopsies. This
      approach to ERCP tissue sampling permits immediate diagnosis and avoids the need
      for subsequent procedures, adds little cost and time, and is safe to perform.

PMID- 21102570
TI  - Differential expression of toll-like receptors in patients with irritable bowel
      syndrome.
AB  - OBJECTIVES: The pathogenesis of irritable bowel syndrome (IBS) is poorly
      understood. One contributory factor may be low-grade mucosal inflammation,
      perhaps initiated by the microbiota. Toll-like receptors (TLRs) are a family of
      pathogen-recognition receptors of the innate immune system. The aim of this study
      was to evaluate the potential involvement of TLRs in IBS to further understand
      the involvement of the innate immune system in this complex disorder. METHODS:
      The expression of TLRs was investigated in colonic biopsy samples obtained from
      26 IBS patients and compared with 19 healthy controls. Protein expression of
      TLR4, TLR7, and TLR8 was confirmed by immunofluorescence and alterations in the
      TLR4 protein were confirmed by western blot. RESULTS: Quantitative reverse
      transcriptase-PCR showed increased levels of TLR4 (P<=0.001) and TLR5 (P=0.0013)
      and decreased levels of TLR7 (P<=0.001) and TLR8 (P=0.0019) in IBS patients.
      CONCLUSIONS: Our results support the presence of an immune engagement between the
      microbiota and the host in IBS; an interaction that involves innate immunity and
      could generate a low-grade inflammatory response. These findings could also offer
      an additional biomarker of the disease or a disease subset.

PMID- 21102571
TI  - The comprehensive ICF core sets for spinal cord injury from the perspective of
      physical therapists: a worldwide validation study using the Delphi technique.
AB  - OBJECTIVE: To validate the International Classification of Functioning,
      Disability and Health (ICF) Core Set for individuals with spinal cord injury
      (SCI) in the early post-acute and long-term context from the perspective of
      physical therapists. SETTING: International. METHODS: Physical therapists
      experienced in the treatment of SCI were asked about problems, resources and
      aspects of the environment treated by them, in a three-round electronic mail
      survey using the Delphi technique. Responses were linked to the ICF by two
      researches; kappa-coefficient was calculated as statistical measure of agreement.
      RESULTS: In all, 81 experts from 27 countries named 3694 concepts. They were
      linked to 187 ICF categories for the early post-acute context. Three ICF
      categories from the component body function, five ICF categories from the
      component body structures and two ICF categories from the component activities
      and participation were not represented in the ICF Core Set for the early post
      acute context. In all, 207 ICF categories were linked for the long-term context.
      Four ICF categories from the component body function, five ICF categories from
      the component body structures and two ICF categories from the component
      activities and participation were not represented in the ICF Core Set for the
      long-term context. CONCLUSION: Physical therapists addressed a vast variety of
      problems that they take care of in their interventions in patients with SCI. The
      Comprehensive ICF Core Sets covered a high percentage of these problems. Further
      research is necessary on several responses not covered in the ICF.

PMID- 21102572
TI  - A global map for traumatic spinal cord injury epidemiology: towards a living data
      repository for injury prevention.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To map traumatic spinal cord injury
      (TSCI) globally and provide a framework for an ongoing repository of data for
      prevention. SETTING: An initiative of the ISCoS Prevention Committee. METHODS:
      The results obtained from the search of Medline/Embase using search phrases: TSCI
      incidence, aetiology, prevalence and survival were analysed. Stratification of
      data into green/yellow/red quality 'zones' allowed comparison between data.
      RESULTS: Reported global prevalence of TSCI is insufficient (236-1009 per
      million). Incidence data was comparable only for regions in North America (39 per
      million), Western Europe (15 per million) and Australia (16 per million). The
      major cause of TSCI in these regions involves four-wheeled motor vehicles, in
      contrast to South-east Asia where two-wheeled (and non-standard) road transport
      predominates. Southern Asia and Oceania have falls from rooftops and trees as the
      primary cause. High-fall rates are also seen in developed regions with aged
      populations (Japan/Western Europe). Violence/self-harm (mainly firearm-related)
      was higher in North America (15%) than either Western Europe (6%) or Australia
      (2%). Sub-Saharan Africa has the highest reported violence-related TSCI in the
      world (38%). Rates are also high in north Africa/Middle East (24%) and Latin
      America (22%). Developed countries have significantly improved TSCI survival
      compared with developing countries, particularly for tetraplegia. Developing
      countries have the highest 1-year mortality rates and in some countries in sub
      Saharan Africa the occurrence of a spinal injury is likely to be a fatal
      condition within a year. CONCLUSION: Missing prevalence and insufficient
      incidence data is a recurrent feature of this review. The piecemeal approach to
      epidemiological reporting of TSCI, particularly failing to include sound regional
      denominators has exhausted its utility. Minimum data collection standards are
      required.

PMID- 21102573
TI  - Do gastrointestinal transit times and colonic dimensions change with time since
      spinal cord injury?
AB  - STUDY DESIGN: Long-term follow-up study. OBJECTIVES: To determine whether
      gastrointestinal transit times (GITTs) and colonic dimensions change during the
      first or subsequent decades after spinal cord injury (SCI). SETTING: Aarhus
      University Hospital, Denmark. METHODS: GITT and colonic dimensions were evaluated
      by means of radio-opaque markers. Group A (n=12) was investigated 1 year after
      SCI and again 13 (range 11-14) years later. Group B (n=10) was studied 19 (range
      9-36) years after injury and again 12 (range 11-12) years later. All had been
      treated with conservative bowel management. RESULTS: In group A, the median GITT
      1 year after injury was 4.3 (range 1.1-6.5) days and 13 years later, it was 3.2
      (range 1.3-6.5) days, P=0.96. In group B, the median GITT 19 year after injury
      was 3.4 (range 0.6-5.9) days and 12 years later, it was 3.2 (range 1.9-5.5) days,
      P=0.77. None of the two groups experienced a significant change in the diameter
      of the caecum/ascending colon, transverse colon, descending colon or the sigmoid
      during long-term follow-up. Megacolon was present in four patients at baseline
      and in five at follow-up. CONCLUSION: GITTs and colonic dimensions did not
      change, neither during the first decade nor long after SCI.

PMID- 21102574
TI  - Comparison of lower extremity motor score parameters for patients with motor
      incomplete spinal cord injury using gait parameters.
AB  - STUDY DESIGN: Retrospective investigation using gait analysis and medical
      records. OBJECTIVE: To evaluate the relationship between ambulatory function
      improvement and an increase in lower-limb motor scores in persons with motor
      incomplete spinal cord injury (SCI) and to compare the efficiency of lower
      extremity motor score (LEMS) and ambulatory motor index (AMI) in representation
      of ambulatory function improvement using gait analysis. SETTING: SCI Unit, Yonsei
      Rehabilitation Hospital, Seoul, Korea. METHODS: The gait analysis from 43
      patients with SCI (paraplegic, n=22, tetraplegic n=21) were reviewed. The gait
      analysis data were obtained with Vicon 370 system. The LEMS and AMI were assessed
      before the gait analysis and the influence of an increase in lower-limb motor
      scores were investigated with linear parameters of gait analysis. RESULTS: For
      group including both tetraplegic and paraplegic patients, both AMI and LEMS were
      statistically correlated with gait speed, step length and negative correlation
      with double-limb support. However, only LEMS was correlated with cadence. For the
      paraplegic group, with AMI and LEMS, there were correlation with gait speed, step
      length and right single-limb support and negative correlation with right double
      limb support. However, only LEMS was correlated with left cadence and negative
      correlation with double-limb support. For the tetraplegic group, only left
      cadence was statistically correlated with AMI. CONCLUSION: Both AMI and LEMS were
      useful in terms of providing information for capability of ambulatory function
      for the paraplegic group. However, for the tetraplegic group, both AMI and LEMS
      do not provide sufficient information for ambulatory function of the incomplete
      SCI patients.

PMID- 21102575
TI  - Psychological factors affecting alcohol use after spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: The purpose of this study is to assess
      risk factors, including personality and socioeconomic indicators, with alcohol
      use among persons with spinal cord injury (SCI). SETTING: A large rehabilitation
      hospital in the Southeastern United States. METHODS: A total of 1549 participants
      responded to a survey on outcomes after SCI. We used polychotomous logistic
      regression to assess the relationships of personality and socioeconomic factors
      with alcohol use. RESULTS: In this study population, 19.3% were heavy drinkers,
      29.4% moderate and 51.7% abstinent. Annual household income and education were
      both associated with heavy alcohol use, with persons with higher income or
      education more likely to be heavy drinkers. Impulsive sensation seeking,
      neuroticism-anxiety and aggression-hostility were associated with increased odds
      of heavy drinking. CONCLUSION: This study adds to the body of evidence indicating
      a substantial portion of individuals with SCI are heavy drinkers, and that
      personality and socioeconomic status are associated with heavy drinking.

PMID- 21102580
TI  - The role of microRNAs in liver cancer progression.
AB  - Primary liver cancer, predominantly consisting of hepatocellular carcinoma (HCC),
      is one of the most common and aggressive human malignancies worldwide. MicroRNAs
      (miRNAs) are a class of small non-coding RNAs that regulate gene expression post
      transcriptionally. Emerging evidence indicates that miRNAs are often deregulated
      in HCC, and that some specific miRNAs are associated with the clinicopathological
      features of HCC. Recent work demonstrates that miRNAs have essential roles in HCC
      progression and directly contribute to cell proliferation, avoidance of apoptotic
      cell death, and metastasis of HCC by targeting a large number of critical protein
      coding genes. The discovery of the aberrantly expressed miRNAs and their
      corresponding targets has opened a novel avenue to investigate the molecular
      mechanism of HCC progression and to develop potential therapeutics against HCC.
      In this review, we summarise current knowledge about the roles and validated
      targets of miRNAs in liver cancer progression.

PMID- 21102581
TI  - Silica dust, diesel exhaust, and painting work are the significant occupational
      risk factors for lung cancer in nonsmoking Chinese men.
AB  - BACKGROUND: Few epidemiological studies have explored the associations between
      occupational exposures and lung cancer in lifelong nonsmoking men. METHODS: We
      obtained lifetime occupational history and other relevant information for 132
      newly diagnosed lung cancer cases among nonsmoking Chinese men and 536 nonsmoking
      community referents. Unconditional multiple logistic regression analysis was
      performed to estimate the odds ratio (OR) of lung cancer for specific
      occupational exposures. RESULTS: Significantly increased lung cancer risk was
      found for nonsmoking workers occupationally exposed to silica dust (OR=2.58, 95%
      confidence interval (CI): 1.11, 6.01), diesel exhaust (OR=3.47, 95% CI: 1.08,
      11.14), spray painting (OR=2.81, 95% CI: 1.14, 6.93), and nonspray painting work
      (OR=2.36, 95% CI: 1.04, 5.37). Silica dust exposure was associated with a
      significantly increased risk of adenocarcinoma (OR=2.91, 95% CI: 1.10, 7.68). We
      observed a positive gradient of all lung cancers and of adenocarcinoma with
      duration of employment for workers exposed to silica dust and spray painting.
      CONCLUSION: This study found an increased risk of lung cancer among nonsmoking
      Chinese men occupationally exposed to silica dust, diesel exhaust, and painting
      work.

PMID- 21102582
TI  - Regulation of PTEN expression by the SWI/SNF chromatin-remodelling protein BRG1
      in human colorectal carcinoma cells.
AB  - BACKGROUND: Aberrant expression of Brahma-related gene-1 (BRG1), a core component
      of the SWI/SNF chromatin-remodelling complex, has been implicated in cancer
      development; however, the biological significance of BRG1 in colorectal carcinoma
      (CRC) remains unknown. METHODS: In CRC tissues, expression of BRG1 and Brahma
      (BRM) was investigated immunohistochemically. Colorectal carcinoma-derived DLD-1
      cells were used for knockdown of BRG1 and PTEN with small interfering RNA (siRNA)
      and transduction of Akt. Complementary DNA (cDNA) microarray analysis was
      performed to explore the genes affected by BRG1. RESULTS: Expression of BRG1, but
      not BRM, was frequently elevated in CRC specimens, and knockdown of BRG1
      suppressed cell proliferation of DLD-1 cells. By cDNA microarray, we determined
      that PTEN expression was negatively regulated by BRG1 in DLD-1 cells, which
      subsequently influenced the cyclin D1 levels via the phosphoinositide 3-OH kinase
      (PI3K)-Akt signalling pathway. The interplay of BRG1 on cyclin D1 expression was
      confirmed by the introduction of Akt and knockdown of PTEN in the BRG1 siRNA
      transduced DLD-1 cells. Interestingly, this positive correlation between BRG1 and
      cyclin D1 expression was also observed in CRC specimens. CONCLUSION: Brahma
      related gene-1 has an important role in the process of CRC development by
      activating the PI3K-Akt signalling pathway and resultant upregulation of cyclin
      D1 levels.

PMID- 21102583
TI  - Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with
      tumour development and progression.
AB  - BACKGROUND: TACE/ADAM17 is a transmembranous protease that cleaves membrane-bound
      growth factors like EGFR ligands. TACE-dependent proteolysis is regulated by its
      inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP3). This study analyses
      the role of TACE and TIMP3 mRNA expression in squamous cell carcinomas of the
      head and neck (HNSCCs). METHODS: We analysed TACE and TIMP3 mRNA expression in
      HNSCCs from 106 patients by RNA in situ hybridisation. RESULTS: TACE mRNA was
      upregulated in HNSCCs compared with dysplastic (P<0.05) and normal epithelia
      (P<0.001), with strong hybridisation signals in 21.9% of invasive tumour tissues
      and 4.5% of dysplasia. Elevated mRNA levels were accompanied by increased amounts
      of TACE protein in HNSCCs. TIMP3 mRNA expression in HNSCC-associated stroma was
      significantly higher than in the stroma adjacent to dysplastic or normal
      epithelia. Expression of TACE mRNA in HNSCCs was associated with tumour stage
      (P=0.019) and regional lymph node metastasis (P=0.009). Furthermore, levels of
      TACE mRNA in HNSCCs correlated with the expression of TIMP3 mRNA in HNSCC
      associated stroma. Concomitantly, patients expressing high levels of TACE and
      TIMP3 mRNA showed significantly reduced overall survival compared with those with
      low mRNA levels. CONCLUSION: Our results indicate an important role of TACE and
      TIMP3 during development and progression of HNSCCs.

PMID- 21102584
TI  - Lymph node density as a surrogate marker for positive lymph nodes.

PMID- 21102585
TI  - Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development.
AB  - The mechanisms controlling mammalian organ size have long been a source of
      fascination for biologists. These controls are needed to both ensure the
      integrity of the body plan and to restrict inappropriate proliferation that could
      lead to cancer. Regulation of liver size is of particular interest inasmuch as
      this organ maintains the capacity for regeneration throughout life, and is able
      to regain precisely its original mass after partial surgical resection. Recent
      studies using genetically engineered mouse strains have shed new light on this
      problem; the Hippo signalling pathway, first elucidated as a regulator of organ
      size in Drosophila, has been identified as dominant determinant of liver growth.
      Defects in this pathway in mouse liver lead to sustained liver overgrowth and the
      eventual development of both major types of liver cancer, hepatocellular
      carcinoma and cholangiocarcinoma. In this review, we discuss the role of Hippo
      signalling in liver biology and the contribution of this pathway to liver cancer
      in humans.

PMID- 21102586
TI  - Inherited polymorphisms in the RNA-mediated interference machinery affect
      microRNA expression and lung cancer survival.
AB  - BACKGROUND: MicroRNAs (miRs) have an important role in lung carcinogenesis and
      progression. Single-nucleotide polymorphisms (SNPs) in genes involved in miR
      biogenesis may affect miR expression in lung tissue and be associated with lung
      carcinogenesis and progression. METHODS: we analysed 12 SNPs in POLR2A, RNASEN
      and DICER1 genes in 1984 cases and 2073 controls from the Environment And
      Genetics in Lung cancer Etiology (EAGLE) study. We investigated miR expression
      profiles in 165 lung adenocarcinoma (AD) and 125 squamous cell carcinoma tissue
      samples from the same population. We used logistic and Cox regression models to
      examine the association of individual genotypes and haplotypes with lung cancer
      risk and with lung cancer-specific survival, respectively. SNPs-miR expression
      associations in cases were assessed using two-sample t-tests and global
      permutation tests. RESULTS: a haplotype in RNASEN (Drosha) was significantly
      associated with shorter lung cancer survival (hazard ratio=1.86, 95% CI=1.19
      2.92, P=0.007). In AD cases, a SNP within the same haplotype was associated with
      reduced RNASEN mRNA expression (P=0.013) and with miR expression changes (global
      P=0.007) of miRs known to be associated with cancer (e.g., let-7 family, miR-21,
      miR-25, miR-126 and miR15a). CONCLUSION: inherited variation in the miR
      processing machinery can affect miR expression levels and lung cancer-specific
      survival.

PMID- 21102587
TI  - Childhood cancer incidence in relation to sunlight exposure.
AB  - BACKGROUND: There is increasing interest in the possible association between
      cancer incidence and vitamin D through its role as a regulator of cell growth and
      differentiation. Epidemiological studies in adults and one paediatric study
      suggest an inverse association between sunlight exposure and cancer incidence.
      METHODS: We carried out an ecological study using childhood cancer registry data
      and two population-level surrogates of sunlight exposure, (1) latitude of the
      registry city or population centroid of the registry nation and (2) annual solar
      radiation. All models were adjusted for nation-level socioeconomic status using
      socioeconomic indicators. RESULTS: Latitude and radiation were significantly
      associated with cancer incidence, and the direction of association was consistent
      between the surrogates. Findings were not consistent across tumour types.
      CONCLUSION: Our ecological study offers some evidence to support an association
      between sunlight exposure and risk of childhood cancer.

PMID- 21102588
TI  - Cost-effectiveness analysis of human papillomavirus DNA testing and Pap smear for
      cervical cancer screening in a publicly financed health-care system.
AB  - OBJECTIVE: to evaluate the long-term cost-effectiveness of different strategies
      for human papillomavirus (HPV) DNA testing combined with Pap smear for cervical
      cancer screening in Taiwan. METHODS: this study adopts a perspective of
      Department of Health in cost-effectiveness analysis to compare a no-screening
      strategy with nine different screening strategies. These strategies comprise
      three screening tools (Pap smear alone, HPV DNA testing followed by Pap smear
      triage, and HPV DNA testing combined with Pap smear), and three screening
      intervals (annually, every 3 years, and every 5 years). Outcomes are life
      expectancy, quality-adjusted life years (QALYs), lifetime costs, and incremental
      cost-effectiveness ratios (ICERs). Probabilistic sensitivity analyses (PSAs) were
      conducted to assess parameter uncertainty. RESULTS: when three times gross
      domestic product per capita is used as the decision threshold, all nine screening
      strategies were cost-effective compared with the no-screening strategy. Compared
      with the current screening strategy (an annual Pap smear), HPV DNA testing
      followed by Pap smear triage every 5 years and every 3 years were cost-effective.
      Results of PSA also indicated that a HPV DNA testing followed by Pap smear triage
      every 5 or every 3 years achieved the highest expected net benefits. CONCLUSIONS:
      possible economic advantages are associated with extending the cervical cancer
      screening interval from one Pap smear annually to HPV DNA testing followed by Pap
      smear triage every 5 years with an ICER $1 247 000 per QALY gained, especially in
      a country with a publicly financed health-care system.

PMID- 21102589
TI  - Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive
      clinical benefit from figitumumab.
AB  - BACKGROUND: Phase III trials of the anti-insulin-like growth factor type 1
      receptor (IGF-IR) antibody figitumumab (F) in unselected non-small-cell lung
      cancer (NSCLC) patients were recently discontinued owing to futility. Here, we
      investigated a role of free IGF-1 (fIGF-1) as a potential predictive biomarker of
      clinical benefit from F treatment. MATERIALS AND METHOD: Pre-treatment
      circulating levels of fIGF-1 were tested in 110 advanced NSCLC patients enrolled
      in a phase II study of paclitaxel and carboplatin given alone (PC) or in
      combination with F at doses of 10 or 20 mg kg(-1) (PCF10, PCF20). RESULTS: Cox
      proportional hazards model interactions were between 2.5 and 3.5 for fIGF-1
      criteria in the 0.5-0.9 ng ml(-1) range. Patients above each criterion had a
      substantial improvement in progression-free survival on PCF20 related to PC
      alone. Free IGF-1 correlated inversely with IGF binding protein 1 (IGFBP-1, rho=
      0.295, P=0.005), and the pre-treatment ratio of insulin to IGFBP-1 was also
      predictive of F clinical benefit. In addition, fIGF-1 levels correlated with
      tumour vimentin expression (rho=0.594, P=0.021) and inversely with E-cadherin
      (rho=-0.389, P=0.152), suggesting a role for fIGF-1 in tumour de-differentiation.
      CONCLUSION: Free IGF-1 may contribute to the identification of a subset of NSCLC
      patients who benefit from F therapy.

PMID- 21102590
TI  - Thyroid cancer risk in Belarus among children and adolescents exposed to
      radioiodine after the Chornobyl accident.
AB  - BACKGROUND: Previous studies showed an increased risk of thyroid cancer among
      children and adolescents exposed to radioactive iodines released after the
      Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency,
      age at exposure and other factors on the dose-response are poorly understood.
      METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at
      the time of the accident who had estimated (131)I thyroid doses based on
      individual thyroid activity measurements and dosimetric data from questionnaires.
      The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear
      exponential functions. RESULTS: For thyroid doses <5 Gy, the dose-response was
      linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher
      doses the excess risk fell. The EOR/Gy was significantly increased among those
      with prior or screening-detected diffuse goiter, and larger for men than women,
      and for persons exposed before age 5 than those exposed between 5 and 18 years,
      although not statistically significant. A somewhat higher EOR/Gy was estimated
      for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl
      accident, thyroid cancer risk was significantly increased among individuals
      exposed to fallout as children or adolescents, but the risk appeared to be lower
      than in other Chornobyl studies and studies of childhood external irradiation.

PMID- 21102591
TI  - Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear
      cell carcinoma?
AB  - BACKGROUND: The growth factor Angiotensin-2 signals through Angiotensin receptor
      type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2
      receptor (AT2-R) in a more restricted group of cell types. Although numerous
      forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2
      R by human renal clear-cell carcinoma (RCCC) is not well understood. In this
      study, the expression of both angiotensin receptors was quantified in a
      retrospective series of RCCC and correlated with prognostic factors. METHODS:
      Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour
      tissues by immunohistochemistry (IHC), western blot and quantitative reverse
      transcriptase PCR (qRT-PCR). IHC results were correlated to Fuhrman's grade and
      patient progression-free survival (PFS). RESULTS: A total of 84 RCCC were
      analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade
      tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a
      correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate
      analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and
      cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be
      overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT
      PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118,
      respectively). CONCLUSION: Our results show that AT1-R and AT2-R proteins are
      overexpressed in the most aggressive forms of RCCC and that AT2-R expression
      correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel
      directions for anti-RCCC therapy.

PMID- 21102593
TI  - Structural characterization of a lipopeptide antibiotic A54145E(Asn3Asp9)
      produced by a genetically engineered strain of Streptomyces fradiae.
AB  - A potent new lipopeptide antibiotic, A54145E(Asn(3)Asp(9)), was isolated from the
      fermentation broth of Streptomyces fradiae DA1489 engineered to delete genes
      encoding enzymes involved in hydroxylation of Asn(3) and methoxylation of Asp(9).
      The chemical structure predicted from the genetic changes in the biosynthetic
      pathway was determined by analyses of chemical transformations, D, L-amino acid
      quantitation by enantiomer labeling, tandem LC-MS/MS and 2D NMR techniques. These
      studies confirmed the primary amino acid sequence of A54145E(Asn(3)Asp(9))
      predicted from the genetic engineering strategy, and also confirmed the structure
      and locations of three D-amino acids predicted from bioinformatic studies.

PMID- 21102592
TI  - Microgeographic variations in Burkitt's lymphoma incidence correlate with
      differences in malnutrition, malaria and Epstein-Barr virus.
AB  - BACKGROUND: Endemic Burkitt's lymphoma (eBL) has been associated with Epstein
      Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. But recent
      evidence suggests that other risk factors are involved. METHODS: We hypothesised
      that selenoprotein glutathione peroxidase (GPx), a surrogate of nutritional
      status, is an important biomarker for eBL risk. We measured plasma GPx,
      anthropometric markers of malnutrition, EBV viral loads and malaria parasitaemia
      in children aged 1-9 years (n=258) from two locations in Nyanza Province, Kenya,
      with higher-than-expected and lower-than-expected incidence of eBL. The study
      participants were malaria asymptomatic children from the community. RESULTS:
      Children from eBL high-incidence areas had significantly lower GPx levels, high
      EBV viral load and more evidence of chronic malnutrition than children from eBL
      low-incidence areas (all P<0.001). Additionally, GPx levels were significantly
      lower in children with the highest EBV viral load and for those with P.
      falciparum infections (P=0.035 and P=0.004, respectively). CONCLUSIONS: These
      results suggest that selenium deficiency may be a risk factor for eBL.

PMID- 21102594
TI  - Generation of reduced macrolide analogs by regio-specific biotransformation.

PMID- 21102595
TI  - Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore
      biosynthesis of quinomycin family antibiotics.
AB  - Quinomycin antibiotics, represented by echinomycin, are an important class of
      antitumor antibiotics. We have recently succeeded in identification of
      biosynthetic gene clusters of echinomycin and SW-163D, and have achieved
      heterologous production of echinomycin in Escherichia coli. In addition, we have
      engineered echinomycin non-ribosomal peptide synthetase to generate echinomycin
      derivatives. However, the biosynthetic pathways of intercalative chromophores
      quinoxaline-2-carboxylic acid (QXC) and 3-hydroxyquinaldic acid (HQA), which are
      important for biological activity, were not fully elucidated. Here, we report
      experiments involving incorporation of a putative advanced precursor, (2S, 3R)
      [6'-(2)H]-3-hydroxy-L-kynurenine, and functional analysis of the enzymes Swb1 and
      Swb2 responsible for late-stage biosynthesis of HQA. On the basis of these
      experimental results, we propose biosynthetic pathways for both QXC and HQA
      through the common intermediate 3-hydroxy-L-kynurenine.

PMID- 21102596
TI  - Production of novel lipopeptide antibiotics related to A54145 by Streptomyces
      fradiae mutants blocked in biosynthesis of modified amino acids and assignment of
      lptJ, lptK and lptL gene functions.
AB  - A54145 is a complex of lipopeptide antibiotics produced by Streptomyces fradiae.
      A54145 factors are structurally related to daptomycin, with four modified amino
      acids, only one of which is present in daptomycin. We generated three mutants
      defective in lptJ, lptK or lptL, whose gene products are involved in the
      formation of hydroxy-Asn(3) (hAsn(3)) and methoxy-Asp(9) (moAsp(9)). Each of the
      mutants produced novel lipopeptides related to A54145 and the profiles allowed
      assignment of functions for those genes. We constructed strains carrying
      different combinations of these genes coupled with a mutation in the lptI gene
      involved in the biosynthesis of 3-methyl-Glu(12) (3mGlu(12)), and all
      recombinants produced novel lipopeptides. One of the compounds displayed very
      good antibacterial activity in the presence of bovine surfactant, which interacts
      with daptomycin or A54145E to inhibit their antibacterial activities.

PMID- 21102597
TI  - A comprehensive overview on genomically directed assembly of aromatic polyketides
      and macrolide lactones using fungal megasynthases.
AB  - Fungal polyketide synthases (PKSs) catalyze a carbon-carbon bond forming reaction
      in an iterative manner using a variety of acyl-CoA molecules as substrates when
      biosynthesizing complex polyketides. Although most members from this class of
      natural products exhibit notable biological activities, often they are naturally
      produced in trace levels or cultivation of the analyte-producing organism is less
      than feasible. Appropriately, to contend with the former challenge, one must
      identify any translational bottleneck and perform functional analysis of the
      associated enzymes. In recent years, many gene clusters purportedly responsible
      for biosynthesizing polyketides have been identified and cataloged from a variety
      of fungal genomes including genes coding for iterative PKSs, particulary
      bikaverin, zearalenone and hypothemycin biosynthetic enzymes. Mounting
      appreciation of these highly specific codons and their translational consequence
      will afford scientists the ability to anticipate the fungal metabolite by
      correlating an organism's genomic cluster to an appropriate biosynthetic system.
      It was observed in recent reports, the successful production of these recombinant
      enzymes using an Escherichia coli expression system which in turn conferred the
      anticipated metabolite in vitro. This review will focus on iterative PKSs
      responsible for biosynthesizing bikaverin, zearalenone and hypothemycin, and
      expand on befitting enzymatic reaction mechanisms and development of a highly
      versatile system that could potentially generate biologically active compounds.

PMID- 21102598
TI  - Modulation of Salmonella gene expression by subinhibitory concentrations of
      quinolones.
AB  - Approximately 2.7% of a collection of Salmonella enterica var. Typhimurium
      promoter-lux reporter strains showed altered transcriptional patterns when
      exposed to low concentrations of nine different fluoroquinolones (FQs). Even at
      the subinhibitory concentrations employed, all nine FQs upregulated genes
      involved in the SOS response, umuD, lexA, sbmC and dinP. In addition,
      transcriptional regulators, genes putatively associated with membrane integrity
      (spr), virulence (sicA) and metabolism (plsB) were affected. Using the Ames test
      with Salmonella strain TA102, increased mutagenicity was demonstrated in response
      to all the FQs tested: ciprofloxacin, moxifloxacin, levofloxacin and
      gatifloxacin. Transcriptional effects were largely specific to the FQ
      antimicrobials. Such responses are consistent with the primary mechanism of
      action of this class of inhibitor, namely, the introduction of DNA damage. This
      work provides support for the notion that small molecules can have functions
      other than growth inhibition that may affect the establishment and maintenance of
      community dynamics in complex environments.

PMID- 21102599
TI  - Bafilomycins produced by an endophytic actinomycete Streptomyces sp. YIM56209.

PMID- 21102600
TI  - Evolutionary dynamics of modular polyketide synthases, with implications for
      protein design and engineering.
AB  - Attempts at generating novel chemistries by genetically manipulating polyketide
      synthases (PKSs) usually result in no detectable or poor product yield.
      Understanding processes that drive the evolution of PKSs might provide a solution
      to this problem. The synonymous-to-non-synonymous nucleotide substitution ratios
      across alignments of well-characterized PKS modules were examined using a sliding
      windows approach. Not surprisingly, the overall substitution ratios showed that
      PKS modules are generally under strong purifying selection, confirming
      experimental observations that changes to the primary amino acid sequence,
      regardless of whether these changes are conservative or not, will most likely
      result in some loss in function. Despite the masking effect of negative
      selection, by judicious choice of window size, it was possible to recognize amino
      acid residues that appear to be under strong positive selection. The importance
      of these amino acids has not been recognized by other analysis methods before and
      we suggest that they may function to 'fine tune' modular PKSs. Future efforts
      will concentrate on understanding if this 'fine tuning' is at the level of
      protein expression, for example, transcription or translation, or at the level of
      protein function, for example, efficient selection and channeling of acyl
      intermediates between domains.

PMID- 21102601
TI  - Cloning of the biosynthetic gene cluster for naphthoxanthene antibiotic FD-594
      from Streptomyces sp. TA-0256.
AB  - FD-594 is an unique pyrano[4',3':6,7]naphtho[1,2-b]xanthene polyketide with a
      trisaccharide of 2,6-dideoxysugars. In this study, we cloned the FD-594
      biosynthetic gene cluster from the producer strain Streptomyces sp. TA-0256 to
      investigate its biosynthesis. The identified pnx gene cluster was 38143 bp,
      consisting of 40 open reading frames, including a minimal PKS gene, TDP-olivose
      biosynthetic genes, two glycosyltransferase genes, two methyltransferase genes
      and many oxygenase/reductase genes. Most of these enzymes coded in the pnx
      cluster were reasonably assigned to a plausible biosynthetic pathway for FD-594,
      in which an unique ring opening process via Baeyer-Villiger-type oxidation
      catalyzed by a putative flavin adenine dinucleotide (FAD)-dependent
      monooxygenase, is speculated to lead to the unique xanthene structure. To clarify
      the involvement of pnx genes in the FD-594 biosynthesis, a glycosyltransferase,
      PnxGT2, and a methyltransferase, PnxMT2, were characterized enzymatically with
      the recombinant proteins expressed in Escherichia coli. As a result, PnxGT2
      catalyzed the triple olivose transfers to the FD-594 aglycon with TDP-olivose as
      the glycosyl donor to afford triolivoside. Surprisingly, in the PnxGT2 enzymatic
      reaction, tetraolivoside and pentaolivoside were significantly detected along
      with the expected triolivoside. To our knowledge, PnxGT2 is the first contiguous
      oligosaccharide-forming glycosyltransferase in secondary metabolism. Furthermore,
      addition of PnxMT2 and S-adenosyl-L-methionine into the PnxGT2 reaction mixture
      afforded natural FD-594 to confirm that the PnxGT2 reaction product was the
      expected regiospecifically glycosylated compound. Consequently, the identified
      pnx gene cluster appears to be involved in FD-594 biosynthesis.

PMID- 21102602
TI  - Iron toxicity in mice with collagenase-induced intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating form of stroke. In this study, we
      examined the efficacy of deferoxamine (DFX), an iron chelator, after collagenase
      induced ICH in 12-month-old mice. Intracerebral hemorrhage was induced by
      intrastriatal injection of collagenase. Deferoxamine (200  mg/kg,
      intraperitoneal) or vehicle was administrated 6  hours after ICH and then every
      12  hours for up to 3 days. Neurologic deficits were examined on days 1 and 3
      after ICH. Mice were killed after 1 or 3 days of DFX treatment for examination of
      iron deposition, neuronal death, oxidative stress, microglia/astrocyte
      activation, neutrophil infiltration, brain injury volume, and brain edema and
      swelling. Collagenase-induced ICH resulted in iron overload in the perihematomal
      region on day 3. Systemic administration of DFX decreased iron accumulation and
      neuronal death, attenuated production of reactive oxygen species, and reduced
      microglial activation and neutrophil infiltration without affecting astrocytes.
      Although DFX did not reduce brain injury volume, edema, or swelling, it improved
      neurologic function. Results of our study indicate that iron toxicity contributes
      to collagenase-induced hemorrhagic brain injury and that reducing iron
      accumulation can reduce neuronal death and modestly improve functional outcome
      after ICH in mice.

PMID- 21102603
TI  - Unconjugated bilirubin contributes to early inflammation and edema after
      intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a stroke subtype with significant mortality and
      morbidity. The role of unconjugated bilirubin (UBR) in ICH brain injury is not
      well understood. Therefore, we studied the effects of UBR on brain injury markers
      and inflammation, as well as mechanisms involved therein. We induced ICH in mice
      by infusion of autologous whole blood with vehicle (dimethyl sulfoxide) or UBR.
      We found that UBR led to an increase in edema (P<=0.05), but a decrease in
      nitrate/nitrite formation (7.0+/-0.40  nmol/mg versus 5.2+/-0.70  nmol/mg
      protein, P<=0.05) and no change in protein carbonyls. Unconjugated bilirubin was
      also associated with an increase in neutrophil infiltration compared with ICH
      alone, as determined by both immunofluorescence and flow cytometry (36%+/-3.2%
      versus 53%+/-1.3% of CD45(+) cells, P<=0.05). In contrast, we observed reduced
      perihematomal microglia immunoreactivity in animals receiving UBR (P<=0.05).
      Using in vitro techniques, we show neutrophil activation by UBR and also show
      that protein kinase C participates in this signaling pathway. Finally, we found
      that UBR was associated with an increased expression of the leukocyte adhesion
      molecule intercellular adhesion molecule-1. Our results suggest that UBR
      possesses complex immune-modulatory and antioxidant effects.

PMID- 21102604
TI  - From MYOD1 to iPS cells.

PMID- 21102605
TI  - Cell cycle: Disposing of SETD8.

PMID- 21102606
TI  - Cell signalling: Cilia downsize mTORC1.

PMID- 21102609
TI  - MET signalling: principles and functions in development, organ regeneration and
      cancer.
AB  - The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue
      remodelling, which underlies developmental morphogenesis, wound repair, organ
      homeostasis and cancer metastasis, by integrating growth, survival and migration
      cues in response to environmental stimuli or cell-autonomous perturbations. The
      versatility of MET-mediated biological responses is sustained by qualitative and
      quantitative signal modulation. Qualitative mechanisms include the engagement of
      dedicated signal transducers and the subcellular compartmentalization of MET
      signalling pathways, whereas quantitative regulation involves MET partnering with
      adaptor amplifiers or being degraded through the shedding of its extracellular
      domain or through intracellular ubiquitylation. Controlled activation of MET
      signalling can be exploited in regenerative medicine, whereas MET inhibition
      might slow down tumour progression.

PMID- 21102610
TI  - Asymmetric cell division: recent developments and their implications for tumour
      biology.
AB  - The ability of cells to divide asymmetrically is essential for generating diverse
      cell types during development. The past 10 years have seen tremendous progress in
      our understanding of this important biological process. We have learned that
      localized phosphorylation events are responsible for the asymmetric segregation
      of cell fate determinants in mitosis and that centrosomes and microtubules play
      important parts in this process. The relevance of asymmetric cell division for
      stem cell biology has added a new dimension to the field, and exciting
      connections between asymmetric cell division and tumorigenesis have begun to
      emerge.

PMID- 21102611
TI  - The SUMO pathway: emerging mechanisms that shape specificity, conjugation and
      recognition.
AB  - Proteins of the small ubiquitin-related modifier (SUMO) family are conjugated to
      proteins to regulate such cellular processes as nuclear transport, transcription,
      chromosome segregation and DNA repair. Recently, numerous insights into
      regulatory mechanisms of the SUMO modification pathway have emerged. Although
      SUMO-conjugating enzymes can discriminate between SUMO targets, many substrates
      possess characteristics that facilitate their modification. Other post
      translational modifications also regulate SUMO conjugation, suggesting that SUMO
      signalling is integrated with other signal transduction pathways. A better
      understanding of SUMO regulatory mechanisms will lead to improved approaches for
      analysing the function of SUMO and substrate conjugation in distinct cellular
      pathways.

PMID- 21102613
TI  - Relationship of serum retinol-binding protein 4 with weight status and lipid
      profile among Korean children and adults.
AB  - BACKGROUND/OBJECTIVES: Although some studies have suggested that retinol-binding
      protein 4 (RBP4), a fat-derived adipokine, is positively related to overweight
      and obesity-related disorders, these claims have been disputed. This study
      investigated relationships between RBP4 level and weight status and metabolic
      disorders in a Korean population including confounding factors, age and gender.
      SUBJECTS/METHODS: From 2005 to 2007, we recruited 570 children and 241 of their
      parents living in Korean urban areas. We analyzed anthropometrical parameters,
      blood pressure, lipid profiles, and levels of serum glucose, insulin, leptin and
      RBP4, and estimated dietary intake based on a self-reported 3-day food diary.
      RESULTS: Levels of RBP4 were high for men (226.2  MUg/ml), mid-range among women
      (143.2 MUg/ml) and low among boys and girls (boys 71.4, girls 66.9  MUg/ml).
      After adjusting for age, gender differences among adults were consistently
      maintained (P<0.0001), and gender differences among children were detected
      minimally (P=0.05). On the basis of Cole's body mass index cutoff points, the
      prevalence of overweight among children was 19.3%. The prevalence among adults
      was 32.0%, based on World Health Organization criteria. Overweight children had
      higher RBP4 concentrations than normal. Overweight women had higher RBP4 levels
      than those of normal weight. Higher RBP4 levels were observed among overweight
      men, but the results were not statistically significant. Triglyceride (TG) levels
      were significantly correlated with RBP4 in all groups. CONCLUSIONS: Our results
      indicate that RBP4 concentrations in a Korean population varied with age, gender
      and overweight status. TG levels could be strongly correlated with RBP4
      concentration.

PMID- 21102612
TI  - Mitochondrial fusion and fission in cell life and death.
AB  - Mitochondria are dynamic organelles that constantly fuse and divide. These
      processes (collectively termed mitochondrial dynamics) are important for
      mitochondrial inheritance and for the maintenance of mitochondrial functions. The
      core components of the evolutionarily conserved fusion and fission machineries
      have now been identified, and mechanistic studies have revealed the first secrets
      of the complex processes that govern fusion and fission of a double membrane
      bound organelle. Mitochondrial dynamics was recently recognized as an important
      constituent of cellular quality control. Defects have detrimental consequences on
      bioenergetic supply and contribute to the pathogenesis of neurodegenerative
      diseases. These findings open exciting new directions to explore mitochondrial
      biology.

PMID- 21102614
TI  - Monitoring vitamin B6 treatment of inflammation in rheumatoid arthritis with
      hemoglobin and ferritin.

PMID- 21102615
TI  - Plasma pyridoxal 5'-phosphate is not correlated with hemoglobin during pyridoxine
      supplementation in patients with rheumatoid arthritis.

PMID- 21102616
TI  - In praise of maize.

PMID- 21102618
TI  - LincRNAs join the pluripotency alliance.

PMID- 21102619
TI  - New mutations and intellectual function.

PMID- 21102620
TI  - FTO gains function.

PMID- 21102622
TI  - Genetic investigation of the origination of allopolyploid with virtually
      synthesized lines: application to the C subgenome of Brassica napus.
AB  - Although there are a number of different allopolyploids in the plant kingdom, the
      exact ancestral parents of some allopolyploids have not been well characterized.
      We propose a strategy in which virtual allopolyploid lines derived from different
      types of parental species are used to investigate the progenitors of an
      allopolyploid. The genotypes of the parental lines and the natural allopolyploid
      were established using a set of DNA molecular markers. The genotypes of the
      virtual lines were then derived from those of the parental lines, and compared
      extensively with that of the natural allopolyploid. We applied this strategy to
      investigate the progenitors of the C subgenome of Brassica napus (rapeseed,
      AACC). A total of 39 accessions from 10 wild and 7 cultivated types of the B.
      oleracea cytodeme (CC), and 4 accessions of B. rapa (AA) were used to construct
      156 virtual rapeseed lines. Genetic structure was compared among natural
      rapeseed, virtual rapeseed lines, and their parental lines by principal component
      analysis and analysis of ancestry. Our data showed that the C subgenome of
      natural rapeseed was related closely to the genome of cultivated B. oleracea and
      its related wild types, such as B. incana, B. bourgeaui, B. montana, B. oleracea
      ssp. oleracea and B. cretica. This finding indicated that these types or their
      progeny might be ancestral donors of the C subgenome of rapeseed. The successful
      application of the strategy of virtual allopolyploidy in rapeseed demonstrates
      that it can possibly be used to identify the progenitors of an allopolyploid
      species.

PMID- 21102623
TI  - ABL at the leading edge.

PMID- 21102624
TI  - Family-based association study of ITGB3 in autism spectrum disorder and its
      endophenotypes.
AB  - The integrin-beta 3 gene (ITGB3), located on human chromosome 17q21.3, was
      previously identified as a quantitative trait locus (QTL) for 5-HT blood levels
      and has been implicated as a candidate gene for autism spectrum disorder (ASD).
      We performed a family-based association study in 281 simplex and 12 multiplex
      Caucasian families. ITGB3 haplotypes are significantly associated with autism
      (HBAT, global P=0.038). Haplotype H3 is largely over-transmitted to the affected
      offspring and doubles the risk of an ASD diagnosis (HBAT P=0.005; odds ratio
      (OR)=2.000), at the expense of haplotype H1, which is under-transmitted (HBAT
      P=0.018; OR=0.725). These two common haplotypes differ only at rs12603582 located
      in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses.
      Interestingly, rs12603582 is strongly associated with pre-term delivery in our
      ASD patients (P=0.008). On the other hand, it is SNP rs2317385, located at the 5'
      end of the gene, that significantly affects 5-HT blood levels (Mann-Whitney U
      test, P=0.001; multiple regression analysis, P=0.010). No gene-gene interaction
      between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a
      significant association between a common ITGB3 haplotype and ASD. Distinct
      markers, located toward the 5' and 3' ends of the gene, seemingly modulate 5-HT
      blood levels and autism liability, respectively. Our results also raise interest
      into ITGB3 influences on feto-maternal immune interactions in autism.

PMID- 21102625
TI  - A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutieres
      syndrome associated with mtDNA deletions.
AB  - Aicardi-Goutieres syndrome (AGS) is a genetic neurodegenerative disorder with
      clinical symptoms mimicking a congenital viral infection. Five causative genes
      have been described: three prime repair exonuclease1 (TREX1), ribonucleases H2A,
      B and C, and most recently SAM domain and HD domain 1 (SAMHD1). We performed a
      detailed clinical and molecular characterization of a family with autosomal
      recessive neurodegenerative disorder showing white matter destruction and
      calcifications, presenting in utero and associated with multiple mtDNA deletions.
      A muscle biopsy was normal and did not show any evidence of respiratory chain
      dysfunction. Southern blot analysis of tissue from a living child and affected
      fetuses demonstrated multiple mtDNA deletions. Molecular analysis of genes
      involved in mtDNA synthesis and maintenance (POLGalpha, POLGbeta, Twinkle, ANT1,
      TK2, SUCLA1 and DGOUK) revealed normal sequences. Sequencing of TREX1 and
      ribonucleases H2A, B and C failed to reveal any mutations. Whole-genome
      homozygosity mapping revealed a candidate region containing the SAMHD1 gene.
      Sequencing of the gene in the affected child and two affected fetuses revealed a
      large deletion (9 kb), spanning the promoter, exon1 and intron 1. The parents
      were found to be heterozygous for this deletion. The identification of a
      homozygous large deletion in the SAMHD1 gene causing atypical AGS with multiple
      mtDNA deletions may add information regarding the involvement of mitochondria in
      self-activation of innate immunity by cell intrinsic components.

PMID- 21102626
TI  - Caution in generalizing known genetic risk markers for breast cancer across all
      ethnic/racial populations.
AB  - Genome-wide association studies (GWAS) have identified common variants associated
      with breast cancer risk among women of European and Asian ancestries. To assess
      the generalizability across ethnic/racial populations of a risk score derived
      from genotyping 12 highly replicated breast cancer GWAS hits, we performed a case
      control study (2224 cases and 2827 controls) nested in the Multiethnic Cohort
      (MEC) study, which was initiated in 1993-1996 and consists of subjects mainly
      from European-American, African-American, Native Hawaiian, Japanese and Latino
      populations. When viewed as a summary risk score, the total number of risk
      alleles carried by women was significantly associated with breast cancer risk
      overall (OR per allele, 1.09; 95% CI, 1.06-1.12; P=2.0 * 10(-10)) and in all
      populations except African-Americans, in which no significant association was
      observed (OR, 1.03; 95% CI, 0.98-1.08). In aggregate, the number of risk alleles
      is strongly associated with breast cancer risk in all populations studied except
      African-Americans. These results emphasize the need for large-scale association
      studies of multiple racial/ethnic groups for discovery and characterization of
      risk alleles relevant to all populations in the United States.

PMID- 21102627
TI  - Experiences with array-based sequence capture; toward clinical applications.
AB  - Although sequencing of a human genome gradually becomes an option, zooming in on
      the region of interest remains attractive and cost saving. We performed array
      based sequence capture using 385K Roche NimbleGen, Inc. arrays to zoom in on the
      protein-coding and immediate intron-flanking sequences of 112 genes, potentially
      involved in mental retardation and congenital malformation. Captured material was
      sequenced using Illumina technology. A data analysis pipeline was built that
      detects sequence variants, positions them in relation to the gene, checks for
      presence in databases (eg, db single-nucleotide polymorphism (SNP)) and predicts
      the potential consequences at the level of RNA splicing and protein translation.
      In the samples analyzed, all known variants were reliably detected, including
      pathogenic variants from control cases and SNPs derived from array experiments.
      Although overall coverage varied considerably, it was reproducible per region and
      facilitated the detection of large deletions and duplications (copy number
      variations), including a partial deletion in the B3GALTL gene from a patient
      sample. For ultimate diagnostic application, overall results need to be improved.
      Future arrays should contain probes from both DNA strands, and to obtain a more
      even coverage, one could add fewer probes from densely and more probes from
      sparsely covered regions.

PMID- 21102628
TI  - Is it time to consider ethnicity in treatment guidelines?

PMID- 21102629
TI  - Heart failure: A SHIFT from ion channels to clinical practice.

PMID- 21102630
TI  - Diabetes: Breaking news! Rosiglitazone and cardiovascular risk.

PMID- 21102631
TI  - Molecular imaging: Measuring myocardial fatty acid metabolism with BMIPP SPECT.

PMID- 21102632
TI  - Interventional cardiology: Hand me your radial artery to protect your kidney.

PMID- 21102633
TI  - SIRT1: recent lessons from mouse models.
AB  - The family of protein deacetylases represented by yeast Sir2 has been the focus
      of intense investigation because of the longevity activity of Sir2 in yeast,
      worms and flies. Research in mammals has mainly focused on SIRT1, the closest
      homologue of Sir2. Emerging evidence from mouse models is yielding a sharper
      picture, in which SIRT1 is a potent protector from ageing-associated pathologies,
      such as diabetes, liver steatosis, cardiovascular disease, neurodegeneration and,
      importantly, various types of cancer.

PMID- 21102634
TI  - Shared and separate functions of polo-like kinases and aurora kinases in cancer.
AB  - Large numbers of inhibitors for polo-like kinases and aurora kinases are
      currently being evaluated as anticancer drugs. Interest in these drugs is fuelled
      by the idea that these kinases have unique functions in mitosis. Within the polo
      like kinase family, the emphasis for targeted therapies has been on polo-like
      kinase 1 (PLK1), and in the aurora kinase family drugs have been developed to
      specifically target aurora kinase A (AURKA; also known as STK6) and/or aurora
      kinase B (AURKB; also known as STK12). Information on the selectivity of these
      compounds in vivo is limited, but it is likely that off-target effects within the
      same kinase families will affect efficacy and toxicity profiles. In addition, it
      is becoming clear that interplay between polo-like kinases and aurora kinases is
      much more extensive than initially anticipated, and that both kinase families are
      important factors in the response to classical chemotherapeutics that damage the
      genome or the mitotic spindle. In this Review we discuss the implications of
      these novel insights on the clinical applicability of polo-like kinase and aurora
      kinase inhibitors.

PMID- 21102635
TI  - Ras superfamily GEFs and GAPs: validated and tractable targets for cancer
      therapy?
AB  - There is now considerable and increasing evidence for a causal role for aberrant
      activity of the Ras superfamily of small GTPases in human cancers. These GTPases
      function as GDP-GTP-regulated binary switches that control many fundamental
      cellular processes. A common mechanism of GTPase deregulation in cancer is the
      deregulated expression and/or activity of their regulatory proteins, guanine
      nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound
      state and GTPase-activating proteins (GAPs) that return the GTPase to its GDP
      bound inactive state. In this Review, we assess the association of GEFs and GAPs
      with cancer and their druggability for cancer therapeutics.

PMID- 21102638
TI  - Can't pay, must pay.

PMID- 21102636
TI  - Integrin signalling adaptors: not only figurants in the cancer story.
AB  - Current evidence highlights the ability of adaptor (or scaffold) proteins to
      create signalling platforms that drive cellular transformation upon integrin
      dependent adhesion and growth factor receptor activation. The understanding of
      the biological effects that are regulated by these adaptors in tumours might be
      crucial for the identification of new targets and the development of innovative
      therapeutic strategies for human cancer. In this Review we discuss the relevance
      of adaptor proteins in signalling that originates from integrin-mediated cell
      extracellular matrix (ECM) adhesion and growth factor stimulation in the context
      of cell transformation and tumour progression. We specifically underline the
      contribution of p130 Crk-associated substrate (p130CAS; also known as BCAR1),
      neural precursor cell expressed, developmentally down-regulated 9 (NEDD9; also
      known as HEF1), CRK and the integrin-linked kinase (ILK)-pinch-parvin (IPP)
      complex to cancer, along with the more recently identified p140 Cas-associated
      protein (p140CAP; also known as SRCIN1).

PMID- 21102639
TI  - Darwin at the edge of the visible universe.

PMID- 21102640
TI  - Is Huntington disease a developmental disorder?

PMID- 21102641
TI  - Stem-cell battles. Stem-cell research in the USA is facing new legal and
      political challenges.

PMID- 21102642
TI  - Facing the credit crunch. Politics sends mixed messages for science in the wake
      of the global financial crisis.

PMID- 21102637
TI  - Why do viruses cause cancer? Highlights of the first century of human tumour
      virology.
AB  - The year 2011 marks the centenary of Francis Peyton Rous's landmark experiments
      on an avian cancer virus. Since then, seven human viruses have been found to
      cause 10-15% of human cancers worldwide. Viruses have been central to modern
      cancer research and provide profound insights into both infectious and non
      infectious cancer causes. This diverse group of viruses reveals unexpected
      connections between innate immunity, immune sensors and tumour suppressor
      signalling that control both viral infection and cancer. This Timeline article
      describes common features of human tumour viruses and discusses how new
      technologies can be used to identify infectious causes of cancer.

PMID- 21102644
TI  - Obesity: maintenance of weight loss: setting our goals higher.

PMID- 21102643
TI  - The Ste20 kinase misshapen is essential for the invasive behaviour of ovarian
      epithelial cells in Drosophila.
AB  - Stationary-to-migratory transitions of epithelial cells have a key role in
      development and tumour progression. Border cell migration is a powerful system in
      which to investigate this transition in living organisms. Here, we identify the
      Ste20-like kinase misshapen (msn) as a novel regulator of border-cell migration
      in Drosophila. Expression of msn in border cells is independent of the
      transcription factor slow border cells and of inputs from all pathways that are
      known to control border-cell migration. The msn gene functions to modulate the
      levels and/or distribution of Drosophila E-cadherin to promote the invasive
      migratory behaviour of border cells.

PMID- 21102645
TI  - Biomarkers: Salivary cortisol or cortisone?

PMID- 21102646
TI  - Nonalcoholic fatty liver disease: liver disease: an overlooked complication of
      diabetes mellitus.

PMID- 21102647
TI  - Postmenopausal hormone therapy: risks versus benefits reassessed.

PMID- 21102648
TI  - Lorcaserin--not a new weapon in the battle with appetite.

PMID- 21102649
TI  - Exposure science for viral diseases: 2009 H1N1 pandemic influenza virus.

PMID- 21102650
TI  - Gene insulation. Part I: natural strategies in yeast and Drosophila.
AB  - This review in two parts deals with the increasing number of processes known to
      be used by eukaryotic cells to protect gene expression from undesired genomic
      enhancer or chromatin effects, by means of the so-called insulators or barriers.
      The most advanced studies in this expanding field concern yeasts and Drosophila
      (this article) and the vertebrates (next article in this issue). Clearly, the
      cell makes use of every gene context to find the appropriate, economic, solution.
      Thus, besides the elements formerly identified and specifically dedicated to
      insulation, a number of unexpected elements are diverted from their usual
      function to structure the genome and enhancer action or to prevent
      heterochromatin spreading. They are, for instance, genes actively transcribed by
      RNA polymerase II or III, partial elements of these transcriptional machineries
      (stalled RNA polymerase II, normally required by genes that must respond quickly
      to stimuli, or TFIIIC bound at its B-box, normally required by RNA polymerase III
      for assembly of the transcription initiation complex at tRNA genes), or genomic
      sequences occupied by variants of standard histones, which, being rapidly and
      permanently replaced, impede heterochromatin formation.

PMID- 21102651
TI  - Gene insulation. Part II: natural strategies in vertebrates.
AB  - The way a gene is insulated from its genomic environment in vertebrates is not
      basically different from what is observed in yeast and Drosophila (preceding
      article in this issue). If the formation of a looped chromatin domain, whether
      generated by attachment to the nuclear matrix or not, has become a classic way to
      confine an enhancer to a specific genomic domain and to coordinate, sequentially
      or simultaneously, gene expression in a given program, its role has been extended
      to new networks of genes or regulators within the same gene. A wider definition
      of the bases of the chromatin loops (nonchromosomal nuclear structures or genomic
      interacting elements) is also available. However, whereas insulation in
      Drosophila is due to a variety of proteins, in vertebrates insulators are still
      practically limited to CTCF (the CCCTC-binding factor), which appears in all
      cases to be the linchpin of an architecture that structures the assembly of DNA
      protein interactions for gene regulation. As in yeast and Drosophila, the economy
      of means is the rule and the same unexpected diversion of known transcription
      elements (active or poised RNA polymerases, TFIIIC elements out of tRNA genes,
      permanent histone replacement) is observed, with variants peculiar to CTCF. Thus,
      besides structuring DNA looping, CTCF is a barrier to DNA methylation or
      interferes with all sorts of transcription processes, such as that generating
      heterochromatin.

PMID- 21102652
TI  - Characterization of LRRFIP1.
AB  - LRRFIP1 has been identified as a regulator of toll-like receptor (TLR) pathway
      signaling; however, little is known about its own regulation and function. This
      study was undertaken to characterize the biochemical properties and its
      regulation. Over-expression of full length LRRFIP1 led to enhanced responses to
      lipopolysaccharide (LPS). We examined its expression in monocytic cell lines
      because they express a broad range of TLRs. We found that its level of expression
      was not altered by LPS or phorbol myristate acetate (PMA) but that it was up
      regulated by nicotine, influenza infection, and serum starvation. Phosphorylation
      was examined because of the bioinformatically predicted serine phosphorylation
      sites. Serine phosphorylation was detected and was altered by both poly I:C and
      nicotine. Finally, we examined the regulation of intracellular localization in
      response to dsRNA and found that LRRFIP1 colocalized with labeled dsRNA in
      monocyte lysosomal structures but not with lysosomes lacking dsRNA. These data
      suggest that LRRFIP1 is phosphorylated in response to immunologic stimuli and it
      is directed to lysosomal structures.

PMID- 21102653
TI  - Chitosanase from Streptomyces coelicolor A3(2): biochemical properties and role
      in protection against antibacterial effect of chitosan.
AB  - Chitosan, an N-deacetylated derivative of chitin, has attracted much attention as
      an antimicrobial agent against fungi, bacteria, and viruses. Chitosanases, the
      glycoside hydrolases responsible for chitosan depolymerisation, are intensively
      studied as tools for biotechnological transformation of chitosan. The chitosanase
      CsnA (SCO0677) from Streptomyces coelicolor A3(2) was purified and characterized.
      CsnA belongs to the GH46 family of glycoside hydrolases. However, it is secreted
      efficiently by the Tat translocation pathway despite its similarity to the well
      studied chitosanase from Streptomyces sp. N174 (CsnN174), which is preferentially
      secreted through the Sec pathway. Melting point determination, however, revealed
      substantial differences between these chitosanases, both in the absence and in
      the presence of chitosan. We further assessed the role of CsnA as a potential
      protective enzyme against the antimicrobial effect of chitosan. A Streptomyces
      lividans TK24 strain in which the csnA gene was inactivated by gene disruption
      was more sensitive to chitosan than the wild-type strain or a chitosanase
      overproducing strain. This is the first genetic evidence for the involvement of
      chitosanases in the protection of bacteria against the antimicrobial effect of
      chitosan.

PMID- 21102654
TI  - Effect of FKBP65, a putative elastin chaperone, on the coacervation of
      tropoelastin in vitro.
AB  - FKBP65 is a protein of the endoplasmic reticulum that is relatively abundant in
      elastin-producing cells and is associated with tropoelastin in the secretory
      pathway. To test an earlier suggestion by Davis and co-workers that FKBP65 could
      act as an intracellular chaperone for elastin, we obtained recombinant FKBP65
      (rFKBP65) by expressing it in E. coli and examined its effect on the coacervation
      characteristics of chicken aorta tropoelastin (TE) using an in vitro
      turbidimetric assay. Our results reveal that rFKBP65 markedly promotes the
      initiation of coacervation of TE without significantly affecting the temperature
      of onset of coacervation. This effect shows saturation at a 1:2 molar ratio of TE
      to rFKBP65. By contrast, FKBP12, a peptidyl prolyl isomerase, has a negligible
      effect on TE coacervation. Moreover, the effect of rFKBP65 on TE coacervation is
      unaffected by the addition of rapamycin, an inhibitor of peptidyl prolyl
      isomerase (PPIase) activity. These observations rule out the involvement of the
      PPIase activity of rFKBP65 in modulating the coacervation of TE. Additional
      experiments using a polypeptide model of TE showed that rFKBP65, while promoting
      coacervation, may retard the maturation of this model polypeptide into larger
      aggregates. Based on these results, we suggest that FKBP65 may act as an elastin
      chaperone in vivo by controlling both the coacervation and the maturation stages
      of its self-assembly into fibrils.

PMID- 21102655
TI  - New nuclear partners for nucleosome assembly protein 1: unexpected associations.
AB  - Histone chaperones are important players in chromatin dynamics. They are
      instrumental in nucleosome assembly and disassembly and in histone variant
      exchange reactions that occur during DNA transactions. The molecular mechanisms
      of their action are not well understood and may involve interactions with various
      protein partners in the context of the nucleus. In an attempt to further
      elucidate nuclear roles of histone chaperones, we performed a proteomic search
      for nuclear partners of a particular histone chaperone, nucleosome assembly
      protein 1 (Nap1). Proteins recognized as Nap1 partners by immuno-affinity capture
      and Far Western blots were identified by mass spectrometry. The identified
      partners are known to participate in a number of nuclear processes, including DNA
      replication, recombination, and repair as well as RNA transcription and splicing.
      Finding nuclear actin among the Nap1 partners may be of particular significance,
      in view of actin's role in transcription, transcription regulation, and RNA
      splicing. We are proposing a model of how actin-Nap1 interaction may be involved
      in transcription elongation through chromatin. In addition, awareness of the
      interactions between Nap1 and Hsp70, another identified partner, may help to
      understand nucleosome dynamics around sites of single-strand DNA break repair.
      These studies represent a starting point for further investigation of Nap1
      associations in human cells.

PMID- 21102656
TI  - Truncation attenuates molecular chaperoning and apoptosis inhibition by p26, a
      small heat shock protein from Artemia franciscana.
AB  - The small heat shock proteins (sHSPs), which prevent irreversible protein
      denaturation and inhibit apoptosis, consist of an amino-terminus, the canonical
      alpha-crystallin domain, and a carboxy-terminal extension. It remains difficult,
      however, to define sHSP structure-function relationships and with this in mind
      p26, an sHSP from the crustacean Artemia franciscana, was truncated by deletion
      mutagenesis. Wild-type p26 cDNA and three truncated variants inserted into the
      eukaryotic expression vector pcDNA3.1/HisC were used to generate stably
      transfected 293H cells. p26 shielded transfected cells against death upon
      exposure to heat and oxidative stress. Truncation reduced chaperone activity,
      with cells synthesizing the p26 alpha-crystallin domain being the least
      resistant. Wild-type p26 inhibited apoptosis in transfected cells, with
      protection against oxidation-generated apoptosis being more effective than that
      against heat-induced apoptosis. Truncation reduced p26 apoptotic inhibitory
      activity, with the alpha-crystallin domain again being the least effective. The
      results show that a crustacean sHSP functions effectively in mammalian cells,
      demonstrating interchangeability of these proteins between distantly related
      organisms and indicating similarities in their mechanisms of action. Moreover,
      maximal activity was observed for full-length p26, indicating that structural
      elements required for chaperone activity and apoptosis inhibition reside
      throughout the protein.

PMID- 21102657
TI  - Lysine 63-linked ubiquitination is important for arachidonic acid-induced
      cellular adhesion and migration.
AB  - Arachidonic acid, a dietary cis-polyunsaturated fatty acid, stimulates adhesion
      and migration of human cancer cells on the extracellular matrix by activation of
      intracellular signaling pathways. Polyubiquitin chains bearing linkages through
      different lysine residues convey distinct structural and functional information
      that is important for signal transduction. We investigated whether ubiquitination
      was required for arachidonic acid-induced cellular adhesion and migration of MDA
      MB-435 cells on collagen type IV. An E1 (ubiquitin-activating enzyme) inhibitor,
      PYR-431, completely abrogated arachidonic acid-stimulated adhesion. Additionally,
      expression of a lysine null mutant ubiquitin prevented activation of cellular
      adhesion. Cells expressing ubiquitin in which lysine 63 (K63) was mutated to
      arginine (K63R) were unable to adhere to collagen upon exposure to arachidonic
      acid. When K63 was the only lysine present, the cells retained the ability to
      adhere, indicating that K63-linked ubiquitin is both necessary and sufficient.
      Moreover, K63-linked ubiquitin was required for the induction of cell migration
      by arachidonic acid. The ubiquitin mutants and PYR-431 did not prevent
      arachidonic acid-induced phosphorylation of TGF-beta activated kinase-1 (TAK1)
      and p38 MAPK, suggesting K63-linked ubiquitination occurs downstream of MAPK.
      These novel findings are the first to demonstrate a role for K63-linked
      ubiquitination in promoting cell adhesion and migration.

PMID- 21102658
TI  - Regulation of liver fatty acid binding protein expression by clofibrate in
      hepatoma cells.
AB  - Peroxisome proliferator-activated receptor (PPAR) agonists such as clofibrate are
      known to affect liver fatty acid binding protein (L-FABP) levels, which in turn
      influence hepatocellular oxidant status. The mechanism of clofibrate's modulation
      of L-FABP levels is not clear. In this study we used clofibrate (PPARalpha
      agonist), MK886 (PPARalpha antagonist), and GW9662 (PPARgamma antagonist) in
      determining the regulating mechanism of L-FABP expression and its antioxidant
      activity in CRL-1548 hepatoma cells. Antioxidant activity was assessed by
      determining intracellular reactive oxygen species (ROS) using dichlorofluorescein
      (DCF) fluorescence. The effect of clofibrate on cytosolic activity of the
      intracellular antioxidant enzymes was also assessed. RT-PCR and mRNA stability
      assay showed that clofibrate treatment enhanced L-FABP mRNA stability, which
      resulted in increased L-FABP levels. A nuclear run-off assay and RT-PCR
      measurements of L-FABP mRNA revealed that clofibrate increased the L-FABP gene
      transcription rate. The increased L-FABP was associated with reduced cytosolic
      ROS. Levels of superoxide dismutase, glutathione peroxidase, and catalase were
      not affected by clofibrate treatment. L-FABP siRNA knockdown studies showed that
      a reduction in L-FABP expression was associated with increased DCF fluorescence.
      We conclude that clofibrate enhanced L-FABP gene transcription and mRNA
      stability, thus affecting L-FABP expression and ultimately cellular antioxidant
      activity.

PMID- 21102660
TI  - Bispectral analysis and recovery of images distorted by a moving water surface.
AB  - We propose a new algorithm to recover a geometrically correct image of an object
      or scene from a set of images distorted by the wave motion of a water surface.
      Under mild conditions where the wavy surface normals weakly satisfy a Gaussian
      distribution, we demonstrate that the geometric distortion can be removed and a
      corrected image can be recovered. Our method is based on higher-order spectra
      analysis-in particular, the bispectrum, similar to its use in astronomical
      speckle imaging. In adapting this technique to imaging through or over a moving
      water surface, special care must be taken, and specifically tailored techniques
      are discussed in this paper. Our algorithm has been tested under two different
      scenarios: the refraction of light through a water surface (the underwater case)
      and the reflection of light from a water surface (the reflection case). Results
      in both cases have been encouraging.

PMID- 21102659
TI  - Importance of Arg-599 of beta-galactosidase (Escherichia coli) as an anchor for
      the open conformations of Phe-601 and the active-site loop.
AB  - Structural and kinetic data show that Arg-599 of beta-galactosidase plays an
      important role in anchoring the "open" conformations of both Phe-601 and an
      active-site loop (residues 794-803). When alanine was substituted for Arg-599,
      the conformations of Phe-601 and the loop shifted towards the "closed" positions
      because interactions with the guanidinium side chain were lost. Also, Phe-601,
      the loop, and Na+, which is ligated by the backbone carbonyl of Phe-601, lost
      structural order, as indicated by large B-factors. IPTG, a substrate analog,
      restored the conformations of Phe-601 and the loop of R599A-beta-galactosidase to
      the open state found with IPTG-complexed native enzyme and partially reinstated
      order. ?-Galactonolactone, a transition state analog, restored the closed
      conformations of R599A-beta-galactosidase to those found with ?-galactonolactone
      complexed native enzyme and completely re-established the order. Substrates and
      substrate analogs bound R599A-beta-galactosidase with less affinity because the
      closed conformation does not allow substrate binding and extra energy is required
      for Phe-601 and the loop to open. In contrast, transition state analog binding,
      which occurs best when the loop is closed, was several-fold better. The higher
      energy level of the enzyme*substrate complex and the lower energy level of the
      first transition state means that less activation energy is needed to form the
      first transition state and thus the rate of the first catalytic step (k2)
      increased substantially. The rate of the second catalytic step (k3) decreased,
      likely because the covalent form is more stabilized than the second transition
      state when Phe-601 and the loop are closed. The importance of the guanidinium
      group of Arg-599 was confirmed by restoration of conformation, order, and
      activity by guanidinium ions.

PMID- 21102661
TI  - Characterization of time-resolved fluorescence response measurements for
      distributed optical-fiber sensing.
AB  - A distributed optical-fiber sensing system based on pulsed excitation and time
      gated photon counting has been used to locate a fluorescent region along the
      fiber. The complex Alq3 and the infrared dye IR-125 were examined with 405 and
      780 nm excitation, respectively. A model to characterize the response of the
      distributed fluorescence sensor to a Gaussian input pulse was developed and
      tested. Analysis of the Alq3 fluorescent response confirmed the validity of the
      model and enabled the fluorescence lifetime to be determined. The intrinsic
      lifetime obtained (18.2+/-0.9 ns) is in good agreement with published data. The
      decay rate was found to be proportional to concentration, which is indicative of
      collisional deactivation. The model allows the spatial resolution of a
      distributed sensing system to be improved for fluorophores with lifetimes that
      are longer than the resolution of the sensing system.

PMID- 21102662
TI  - Membrane photon sieve telescopes.
AB  - We present results of research into the design and construction of membrane
      photon sieves as primaries for next-generation lightweight space telescopes. We
      have created prototypes in electroformed nickel as well as diazo and CP-1 polymer
      films. In two such cases, diffraction-limited imaging performance was
      demonstrated over a narrow bandwidth.

PMID- 21102663
TI  - Tomographic alignment algorithm for an extremely large three-mirror telescope:
      invisible modes.
AB  - We analyze the optical effects due to distortions of a three-mirror telescope
      that is sufficiently large that all three mirrors must be actively controlled.
      Numerical experiments on telescopes with both monolithic and segmented primary
      mirrors reveal the existence of telescope misalignment configurations (modes)
      that are invisible to a fixed focal station wavefront sensor, even for highly
      redundant multidirectional tomographic measurement schemes. We describe these
      modes and give a theoretical explanation for them.

PMID- 21102664
TI  - Slope measurement of a phase object using a polarizing phase-shifting high
      frequency Ronchi grating interferometer.
AB  - An interferometric method to measure the slope of phase objects is presented. The
      analysis was performed by implementing a polarizing phase-shifting cyclic shear
      interferometer coupled to a 4-f Fourier imaging system with crossed high
      frequency Ronchi gratings. This system can obtain nine interference patterns with
      adjustable phase shifts and variable lateral shear. In order to extract the slope
      of a phase object, it is only analyzed using four patterns obtained in a single
      shot, and applying the classical method of phase extraction.

PMID- 21102665
TI  - Simulation method for interference fringe patterns in measuring gear tooth flanks
      by laser interferometry.
AB  - We present a ray-tracing-based method for simulation of interference fringe
      patterns (IFPs) for measuring gear tooth flanks with a two-path interferometer.
      This simulation method involves two steps. In the first step, the profile of an
      IFP is achieved by means of ray tracing within the object path of the
      interferometer. In the second step, the profile of an IFP is filled with
      interference fringes, according to a set of functions from an optical path length
      to a fringe gray level. To examine the correctness of this simulation method,
      simulations are performed for two spur involute gears, and the simulated IFPs are
      verified by experiments using the actual two-path interferometer built on an
      optical platform.

PMID- 21102666
TI  - Simultaneous characterization of the shape and refractive index of transparent
      living cells by an optical aperture.
AB  - We report a method of using optical aperture diffraction to simultaneously detect
      the image and the refractive index of a living cell. By simulation, it is found
      that, when a suitable gap is introduced between the cell and the aperture, the
      image of the cell on the detection plane can be amplified hundreds to thousands
      of times, and a limit of detection of 3e-4 to 9e-5 can be reached for the
      refractive index of the cell. Experiments show that this method is feasible to
      realize, but the achievement of such a detection system is yet to be proved.

PMID- 21102667
TI  - Speckle reduction using orthogonal arrays in laser projectors.
AB  - We propose using a two-level (-1 and +1 as variables) orthogonal array (OA) to
      generate a binary phase diffuser for speckle reduction in laser projection
      displays. Compared with the Hadamard matrix, the diffuser generated from OA is
      more flexible. The speckle contrast ratio (CR) when introducing the binary phase
      diffuser at an intermediate image plane within the projector is calculated, and
      the minimum speckle CR can be achieved by finite step change of the diffuser
      patterns. With Kronecker algebra, the two-dimensional diffuser can also be
      replaced by two one-dimensional diffusers with the same function, and it can be
      implemented into the laser projector electronically and easily.

PMID- 21102668
TI  - Magnified reconstruction of digitally recorded holograms by Fresnel-Bluestein
      transform.
AB  - A method for numerical reconstruction of digitally recorded holograms with
      variable magnification is presented. The proposed strategy allows for smaller,
      equal, or larger magnification than that achieved with Fresnel transform by
      introducing the Bluestein substitution into the Fresnel kernel. The magnification
      is obtained independent of distance, wavelength, and number of pixels, which
      enables the method to be applied in color digital holography and metrological
      applications. The approach is supported by experimental and simulation results in
      digital holography of objects of comparable dimensions with the recording device
      and in the reconstruction of holograms from digital in-line holographic
      microscopy.

PMID- 21102669
TI  - Temperature and pressure imaging using infrared planar laser-induced
      fluorescence.
AB  - A new diagnostic technique for measurements of temperature and pressure
      distribution in gaseous flows has been developed. The technique, based on
      infrared planar laser-induced fluorescence (IR-PLIF), is applicable to all IR
      active species. A simple two-line excitation approach is used for measurements of
      temperature, while pressure measurements utilize online excitation on one
      rotational line and offline excitation on another. A demonstration of the
      technique in a supersonic underexpanded jet of 30% CO2 and 70% N2 was performed,
      and the results are, to the best of our knowledge, the first demonstration of
      temperature and pressure imaging using IR-PLIF. The developed diagnostic shows
      potential for single-shot two-dimensional measurements of temperature and
      pressure in gaseous flows.

PMID- 21102670
TI  - Microlens characterization by digital holographic microscopy with physical
      spherical phase compensation.
AB  - Microlenses have been characterized by a digital holographic microscopy system,
      which is immune to the inherent wavefront aberration. The digital holographic
      microscopy system takes advantage of fiber optics and uses the light emitted
      directly from a single-mode fiber as the recording reference wave. By using such
      a reference beam, which is quasi-identical to the object beam, the inherent
      wavefront aberration of the digital holographic microscope is removed. The
      alignment of the optical setup can be optimized with the help of numerical
      reconstruction software to give the system phase with the off-axis tilt removed.
      There is one, and only one, reference fiber point position to give a reference
      wavefront that is quasi-identical to the object wavefront where the system is
      free of wavefront aberration and directly gives the quantitative phase of the
      test object without the need for complicated numerical compensation.

PMID- 21102671
TI  - Design of a high-efficiency grating coupler based on a silicon nitride overlay
      for silicon-on-insulator waveguides.
AB  - A waveguide grating coupler based on a silicon nitride overlay at 1.55 MUm for TE
      polarization is designed with no experimental demonstration. Its coupling
      efficiency for a fiber is 76%, the 1 dB bandwidth is 75 nm, and the coupling
      angle is 10 degrees . The effects of different device parameters on the coupling
      performance for the grating coupler are discussed. The coupling efficiency of our
      grating coupler is almost equal, yet the 1 dB spectral bandwidth is around 25 nm
      broader, as compared with the grating coupler design based on a poly-silicon
      overlay. The coupling performance of our coupling device could still be further
      improved. The grating coupler presented in this paper is applicable to the
      optical coupling in nanophotonic integrated circuits.

PMID- 21102672
TI  - Ultrasensitive chemical sensors based on whispering gallery modes in a
      microsphere coated with zeolite.
AB  - We propose a highly sensitive chemical sensor by functionally coating a zeolite
      film on the external surface of an optical microsphere. Using the perturbation
      theory, a model is developed to calculate sensor sensitivity and analyze the
      impact of the zeolite film thickness. The quality factor and detection limit are
      also investigated by using an approximate model. Simulations show that a zeolite
      coating can effectively increase sensitivity. The results provide physical
      insights for the design and optimization of various parameters for desired sensor
      performance.

PMID- 21102673
TI  - Improved Newton-Raphson digital image correlation method for full-field
      displacement and strain calculation.
AB  - The two-dimensional in-plane displacement and strain calculation problem through
      digital image processing methods has been studied extensively in the past three
      decades. Out of the various algorithms developed, the Newton-Raphson partial
      differential correction method performs the best quality wise and is the most
      widely used in practical applications despite its higher computational cost. The
      work presented in this paper improves the original algorithm by including
      adaptive spatial regularization in the minimization process used to obtain the
      motion data. Results indicate improvements in the strain accuracy for both small
      and large strains. The improvements become even more significant when employing
      small displacement and strain window sizes, making the new method highly suitable
      for situations where the underlying strain data presents both slow and fast
      spatial variations or contains highly localized discontinuities.

PMID- 21102674
TI  - Linearized electro-optic modulators based on a two-section Y-fed directional
      coupler.
AB  - We experimentally demonstrate a linearized Y-fed directional coupler (DC)
      modulator based on an electro-optic (EO) polymer waveguide. The spurious free
      dynamic range of 119 dB/Hz2/3, which is 11 dB higher than that of the
      conventional Mach-Zehnder modulator, is achieved by introducing the reversed
      Deltabeta technique in the two-section Y-fed DC. The in-device EO coefficient
      (r33) of the fabricated device is as high as 79 pm/V in 1.55 MUm wavelength,
      which is 88% of a single film r33 of LPD-80/APC.

PMID- 21102675
TI  - Systematic comparison of the use of annular and Zernike circle polynomials for
      annular wavefronts.
AB  - The theory of wavefront analysis of a noncircular wavefront is given and applied
      for a systematic comparison of the use of annular and Zernike circle polynomials
      for the analysis of an annular wavefront. It is shown that, unlike the annular
      coefficients, the circle coefficients generally change as the number of
      polynomials used in the expansion changes. Although the wavefront fit with a
      certain number of circle polynomials is identically the same as that with the
      corresponding annular polynomials, the piston circle coefficient does not
      represent the mean value of the aberration function, and the sum of the squares
      of the other coefficients does not yield its variance. The interferometer setting
      errors of tip, tilt, and defocus from a four-circle-polynomial expansion are the
      same as those from the annular-polynomial expansion. However, if these errors are
      obtained from, say, an 11-circle-polynomial expansion, and are removed from the
      aberration function, wrong polishing will result by zeroing out the residual
      aberration function. If the common practice of defining the center of an
      interferogram and drawing a circle around it is followed, then the circle
      coefficients of a noncircular interferogram do not yield a correct representation
      of the aberration function. Moreover, in this case, some of the higher-order
      coefficients of aberrations that are nonexistent in the aberration function are
      also nonzero. Finally, the circle coefficients, however obtained, do not
      represent coefficients of the balanced aberrations for an annular pupil. The
      various results are illustrated analytically and numerically by considering an
      annular Seidel aberration function.

PMID- 21102677
TI  - Composite quarter-wave systems with adjustable parameters.
AB  - A new type of composite quarter-wave system with adjustable parameters has been
      proposed and investigated experimentally. The first system is a quarter-waveplate
      with adjustable optical activity and the second system is a quarter-wave plate
      with an adjustable axis orientation.

PMID- 21102678
TI  - Femtosecond laser-induced thermal lens effect in chromium film.
AB  - The thermal lens (TL) effect induced by femtosecond laser pulses in chromium film
      is reported. A Fresnel diffraction theory is used to explain the TL effect. The
      intensity profile of the TL calculated by the theoretical model is in agreement
      with the experimental results. The contrast ratio of the TL is defined to
      describe the TL effect, and we find that the maximum contrast ratio of the TL
      effect is obtained when the probe beam is recorded at a characteristic distance.
      The dependence of the contrast ratio of the TL on different pump laser power
      levels and delay times is also investigated. Numerical simulations are also
      consistent with the experimental results.

PMID- 21102679
TI  - Effects of structured mid-spatial frequency surface errors on image performance.
AB  - Optical designers are encouraged to adopt aspheric and free-form surfaces into an
      increasing number of design spaces because of their improved performance.
      However, residual tooling marks from advanced aspheric fabrication techniques are
      difficult to remove. These marks, typically in the mid-spatial frequency (MSF)
      regime, give rise to structured image artifacts. Using a theory developed in
      previous publications, this paper applies the fundamentals of MSF modeling to
      demonstrate how MSF errors are evaluated and toleranced in an optical system.
      Examples of as-built components with MSF errors are analyzed using commercial
      optical design software.

PMID- 21102680
TI  - Two-dimensional scattering from a multilayered periodic structure of arbitrary
      shapes.
AB  - A numerical approach is presented to analyze the two-dimensional scattering
      properties from a multilayered periodic dielectric structure of an arbitrary
      number of arbitrarily shaped unit cells. The approach is enhanced by the periodic
      moment method, the lattice sums technique, and the Poisson summation formula. The
      matrix element's evaluation accounts for the overall coupling between layers. The
      choosing of lattice parameters allows designs for a wide range of applications,
      including the electromagnetic bandgap filtering of an E-polarized wave, which is
      simulated and reported here.

PMID- 21102681
TI  - Microwave photonic notch filter based on a dual-Sagnac-loop structure.
AB  - A new single-wavelength, coherence-free microwave photonic notch filter is
      presented. The concept is based on a dual-Sagnac-loop structure that functions
      with a new principle in which the two loops operate with different free spectral
      ranges, and which generate noncommensurate taps. It has the ability to generate a
      narrow notch response and can operate to high frequencies. Experimental results
      demonstrate a notch filter with a narrow notch width, a flat passband, and high
      stop-band attenuation of over 40dB.

PMID- 21102682
TI  - Thickness measurement of transparent glass plates using a lateral shearing cyclic
      path optical configuration setup and polarization phase shifting interferometry.
AB  - We present a measurement technique to determine the thickness of a transparent
      glass plate (GP) by using a lateral shearing cyclic path optical configuration
      (CPOC) setup and polarization phase shifting interferometry (PPSI). In the
      technique, the GP introduces a longitudinal shift in the focus of the beam and,
      as a result, a spherical wavefront emerges from the lens, which is otherwise set
      for producing a collimated beam. Using CPOC, two laterally sheared orthogonally
      polarized beams are generated from the incident spherical wavefront. By applying
      PPSI, the slope of the optical path difference variation between the laterally
      sheared interfering beams is evaluated, and the radius of the spherical wavefront
      and the longitudinal shift of the beam focus are calculated. The thickness of the
      GP is determined from the standard relation between the longitudinal shift of the
      focus introduced by the GP and the thickness of the GP. Results obtained for a GP
      of 9.810mm thickness are presented.

PMID- 21102683
TI  - Picosecond optical parametric chirped pulse amplifier as a preamplifier to
      generate high-energy seed pulses for contrast enhancement.
AB  - We present the design, implementation, and testing of a novel picosecond optical
      parametric preamplifier system to generate high-energy seed pulses for the Vulcan
      laser facility. The preamplifier amplifies 100 fs pulses stretched to 3 ps pulses
      from 10 pJ to 70 MUJ in a single stage of amplification before the pulses are
      further amplified in the Vulcan high-power Nd:glass laser facility to the
      petawatt power level. This increased seed energy has led to an improvement of the
      nanosecond amplified spontaneous emission contrast intensity to 10(-10) of the
      main pulse, without degrading the output of the laser system.

PMID- 21102684
TI  - Noise filtering in the interference pattern by dynamic holographic recording in
      photorefractive Bi(12)TiO(20) crystals.
AB  - The possibilities of stabilization of the interference pattern by filtration of a
      random-phase noise caused by vibrations, turbulence, and other local changes in
      the wave front in interferometric measurements are investigated. Dynamic
      holographic recording in photorefractive Bi(12)TiO(20) crystals is used. The
      parameters of the holographic recording are presented for determination of the
      dynamic range for filtering. Noise filtering takes place in real time and
      contributes to the enhancement of the contrast and the signal-to-noise ratio of
      the interference pattern. This results in a considerable increase in the
      sensitivity and the accuracy of the interferometric measurements.

PMID- 21102685
TI  - Phase-only joint-transform correlator: analysis and experimental results.
AB  - An analysis of the popular joint-transform optical correlator is presented for
      architectures employing spatial light modulators that operate only on the phase
      of the coherent light. Experimental results are also presented, for simple scenes
      that produce analytic solutions, which support the analysis.

PMID- 21102686
TI  - Measurement of the spatial phase modulation of a ferroelectric liquid-crystal
      modulator.
AB  - Ferroelectric liquid crystal is used as a dynamic light-wave phase modulator. A
      device that performs phase-only modulation is investigated, especially with
      regard to the boundary effect caused by the inevitable gap between controlling
      electrodes. The dependence of cell retardation and polarizer alignment is
      discussed. Two phase-retrieving algorithms are used to determine the complex
      lightwave front after traversing the device. In operation it was found that the
      electrode gap region was partly controlled.

PMID- 21102687
TI  - Improved imagery through scattering materials by quasi-Fourier-synthesis
      holography.
AB  - An improvement on the technique of Fourier-synthesis holography is proposed and
      demonstrated. Artifacts produced during the process of sampling are eliminated
      when the laser is swept over a continuous bandwidth between samples. The
      advantages of Fourier-synthesis holography, such as the ability to select the
      gating time delay and to shape the autocorrelation function after data
      acquisition, are retained.

PMID- 21102688
TI  - Optical intrinsically fuzzy mathematical morphology for gray-scale image
      processing.
AB  - Intrinsically fuzzy morphological erosion and dilation are extended to a total of
      eight operations that have been formulated in terms of a single morphological
      operation-biased dilation. Based on the spatial coding of a fuzzy variable, a
      bidirectional projection concept is proposed. Thus, fuzzy logic operations,
      arithmetic operations, gray-scale dilation, and erosion for the extended
      intrinsically fuzzy morphological operations can be included in a unified
      algorithm with only biased dilation and fuzzy logic operations. To execute this
      image algebra approach we present a cellular two-layer processing architecture
      that consists of a biased dilation processor and a fuzzy logic processor.

PMID- 21102689
TI  - Optical wavelet transform by the phase-only joint-transform correlator.
AB  - A method is presented that performs the optical wavelet transform with liquid
      crystal televisions as spatial light modulators operating only on the phase of
      the incident coherent light. The architecture is the joint-transform correlator,
      and the wavelets and the image to be transformed are encoded in the input plane
      of the system. The mathematical formalism describing the adaptation of the joint
      transform correlator to the wavelet transform is given and extended to the
      operation of the phase-only joint-transform correlator. A new wavelet is
      described for two-dimensional image processing, and experimental results are
      presented for optical wavelet transforms done in real time by use of this wavelet
      in the phase-only joint-transform-correlator architecture. The analysis is
      extended to multiwavelet (multispectral) analysis by the joint-transform
      correlator, and simulation results are given. Finally experimental results with
      the phase-only joint-transform correlator applied to multi-wavelet analysis are
      presented.

PMID- 21102690
TI  - Distance-classifier correlation filters for multiclass target recognition.
AB  - We describe a correlation-based distance-classifier scheme for the recognition
      and the classification of multiple classes. The underlying theory uses shift
      invariant filters to compute distances between the input image and ideal
      references under an optimum transformation. The original distance-classifier
      correlation filter was developed for a two-class problem. We introduce a distance
      classifier correlation filter that simultaneously considers multiple classes, and
      we show that the earlier two-class formulation is a special case of the
      classifier presented. Initial results are presented to demonstrate the
      discrimination- and distortion-tolerance capabilities of the proposed filter.

PMID- 21102691
TI  - Incoherent pattern detection using a liquid-crystal active lens.
AB  - Incoherent pattern detection by a simple imaging system using a liquid-crystal
      active lens is proposed. The imaging system works as a spatial filtering system
      with a rewritable phase-only filter. We found that, in the incoherent matched
      filtering system, a conventional phase-only filter has a higher optical
      efficiency but a lower pattern discrimination than a complex filter. To improve
      the pattern discrimination ability, we optimized the phase-only filter by using
      simulated annealing and a genetic algorithm. We designed phase-only filters that
      have discrimination ability comparable with that in a complex filter. The
      performance of optimized phase-only filters is experimentally demonstrated.

PMID- 21102692
TI  - Wavelet-transform-based composite filters for invariant pattern recognition.
AB  - A wavelet-transformation-based optical processor for performing invariant pattern
      recognition is suggested. It contains a composite filter that consists of several
      wavelet daughter functions derived from the reference object. The intensity of
      the correlation peak is determined to be invariant to various deformations of the
      reference object. Computer simulations show explicitly the promising capability
      of the new technique. Laboratory experimental results are given.

PMID- 21102693
TI  - Real-time optical image subtraction and edge enhancement using ferroelectric
      liquid-crystal devices based on speckle modulation.
AB  - We carried out real-time optical image subtraction and edge enhancement based on
      a speckle modulation technique by using ferroelectric liquid-crystal polarization
      switches and a ferroelectric liquid-crystal spatial light modulator. A
      ferroelectric liquid-crystal spatial light modulator is employed as a real-time
      and multiple-exposure optical device, and successful results are obtained from
      three-exposure images modulated by speckles. Thus, image subtraction and edge
      enhancement are realized in real time. The whole operation is performed within
      several milliseconds with modest operating conditions. Because the spatial light
      modulator has a high resolution of greater than 100 line pairs/mm and can store
      fine speckle patterns, the image qualities we obtained are quite satisfactory.

PMID- 21102694
TI  - Electro-optic beam-steering device based on a lanthanum-modified lead zirconate
      titanate ceramic wafer.
AB  - We demonstrate a lanthanum-modified lead zirconate titanate ceramic-based electro
      optic beam-steering device that has a 3 mm * 3 mm working area. A series of
      resistors were made by evaporation of chromium onto the substrate to produce and
      control the required voltage distribution among the electrodes. A steering angle
      of 0.04 degrees  was obtained with an applied voltage of 700 V. Design
      considerations, computer simulations, and experimental results are presented.

PMID- 21102695
TI  - Optical fractional Fourier transforms with complex orders.
AB  - A definition of real and complex domains for the order of fractional Fourier
      transforms is introduced in association with diffraction either in free space or
      through real and complex lenses. The geometrical and the optical conditions that
      lead to real and complex orders of the fractional Fourier transforms and their
      relevance to cascading optical systems are discussed.

PMID- 21102696
TI  - Every Fourier optical system is equivalent to consecutive fractional-Fourier
      domain filtering.
AB  - We consider optical systems composed of an arbitrary number of lenses and
      filters, separated by arbitrary distances, under the standard approximations of
      Fourier optics. We show that every such system is equivalent to (i) consecutive
      filtering operations in several fractional Fourier domains and (ii) consecutive
      filtering operations alternately in the space and the frequency domains.

PMID- 21102697
TI  - Laser-induced breakdown in H2 gas at 248 nm.
AB  - Measurement of optical breakdown threshold in hydrogen gas with a KrF excimer
      laser at 248 nm is presented. The result shows a sharp increase of the threshold
      intensity at a few atmospheres of gas pressure when a focusing lens with a longer
      focal length is used. This enhancement is partially explained in terms of the
      influence of pump beam depletion in stimulated Raman scattering.

PMID- 21102698
TI  - Hybrid stable-unstable resonators for diffusion-cooled CO(2) slab lasers.
AB  - We present the numerical and experimental study that we carried out to compare
      the performances of two hybrid stable-unstable resonators for diffusion-cooled
      CO(2) slab lasers. The two resonators are designed to fit a 320 mm * 60 mm *2 mm
      rf-discharge channel and are both guided in the narrow transverse direction. They
      differ in the other transverse direction, consisting of a positive- or a negative
      branch unstable resonator scheme. The two solutions have been characterized in
      terms of modal structure, power extraction, stability, and quality of the
      extracted beam.

PMID- 21102699
TI  - Photostability of dye molecules trapped in solid matrices.
AB  - The photostability of dye molecules trapped in transparent solid matrices
      synthesized by the solgel technique was studied both experimentally and
      theoretically using a model with numerical and approximate analytical solutions.
      The model is based on a one-photon photodestruction process with the creation of
      an absorbing bleached molecule. We give the number of photons that different
      trapped dye molecules can absorb on average before they are bleached. Dyes such
      as Perylene Red, Perylene Orange, Pyrromethenes 567 and 597, Rhodamines 6G and B,
      DCM, a Xanthylium salt, and Neon Red were investigated; significant differences
      were observed. Some dye molecules in solvents were also studied; increased
      stability resulted when the molecules were trapped in solid matrices.

PMID- 21102700
TI  - Laser-diode-pumped cw Nd:MgO:LiNbO(3) self-frequency-doubling laser around room
      temperature.
AB  - A laser-diode-pumped cw self-frequency-doubling laser has been achieved in
      Nd:MgO:LiNbO3 crystal around room temperature. The second-harmonic output at
      lambda = 547 nm to 8 mW was obtained with a miniature resonator in which only a
      crystal was included, without any extra intracavity component.

PMID- 21102701
TI  - Efficient laser operation of diode-pumped Nd:KGd(WO4)2 crystal at 1.067 um.
AB  - The spectral properties and laser performance of a Nd:KGd(WO(4))(2) (Nd:KGW) rod
      pumped by a laser diode have been studied. The Nd:KGW can be doped with a much
      higher Nd3(+) concentration and has a wider absorption linewidth around 808 nm
      compared with Nd:YAG. At low repetition rates, the Nd:KGW exhibited good lasing
      properties with a lower threshold. The maximum optical-to-optical conversion
      efficiency of the diode laser pumped Nd:KGW laser at 1.067 um has been determined
      to be 34.3% with a slope efficiency of 43.1%.

PMID- 21102702
TI  - Frequency-stabilized high-power ruby laser Q switched by Rb(2) vapor.
AB  - Passive Q switching of a ruby laser by the use of molecular rubidium (Rb(2))
      vapor has been realized. For the first time, to our knowledge, an integrally
      sapphire cell containing Rb(2) vapor was used as the saturable absorber, which
      ensures an operation period of several years. Single-frequency-stabilized giant
      pulses with 700-mJ energy, 22-ns duration, and 200-MHz spectral width were
      obtained.

PMID- 21102703
TI  - Equation of atomic resonance for solid-state optics and exact complex line shapes
      of atomic resonance: corrigenda.

PMID- 21102704
TI  - Second-harmonic generation in second-harmonic fiber Bragg gratings.
AB  - We consider the production of second-harmonic light in gratings resonant with the
      generated field, through a Green's function approach. We recover some standard
      results and obtain new limits for the uniform grating case. With the extension to
      nonuniform gratings, we find the Green's function for the second harmonic in a
      grating with an arbitrary phase shift at some point. We then obtain closed form
      approximate expressions for the generated light for phase shifts close to pi/2
      and at the center of the grating. Finally, comparing the uniform and phase
      shifted gratings with homogeneous materials, we discuss the enhancement in
      generated light and the bandwidth over which it occurs, and the consequences for
      second-harmonic generation in optical fiber Bragg gratings.

PMID- 21102705
TI  - Experimental investigation of new concentration measurements using nonlinear
      dynamics through laser-induced thermal lens oscillation.
AB  - The laser-induced thermal lens oscillation that is generated in an organic
      solution by Ar-ion laser irradiation was studied as a nonlinear dynamic system.
      The different dynamic states depend on three control parameters: laser beam power
      (P), depth (d) from a surface to a laser beam position, and solvent
      concentration. The transitions of dynamic states including several complicated
      states, for example, periodic, double periodic, were investigated by varying the
      parameters (P, d) for 27%, 30%, and 33% of tri-n-butyl phosphate solution diluted
      with n-dodecane. It was found that these transitions were strongly dependent on
      the concentration of the TBP solution. Based on this result, we also propose an
      application to solvent concentration measurement with a difference of 3%.

PMID- 21102706
TI  - Measurement of ultrashort pulse durations by interferometric autocorrelation:
      influence of various parameters.
AB  - The interferometric autocorrelation technique for the measurement of ultrashort
      pulse durations is studied in detail. Effects of group velocity mismatch, group
      velocity dispersion, fundamental depletion, and pulse shape are carefully
      examined. A simple semianalytical calculation is developed that takes group
      velocity mismatch into account that can be used to predict the validity of this
      technique with real experimental parameters. A more complete calculation is also
      presented to analyze the effects of fundamental depletion or phase mismatch.
      Finally, the influence of the pulse shape is considered and a simple experimental
      procedure is proposed to determine whether a pulse is transform limited.

PMID- 21102707
TI  - Direct measurement of reflectance from aluminum alloys during CO(2) laser
      welding.
AB  - A simple method for measuring the reflected amount of a CO(2) laser beam from the
      surface of a welded aluminum alloy is described. This device can be used for
      cases in which an integrating sphere is impractical to use. A pyroelectric
      detector measures the amount of reflected laser radiation at prespecified
      locations that define a semisphere on top of the weld spot. The spatial
      distribution of a reflected laser beam is obtained. It is found that ~80% of the
      total incident power is reflected by the alloy until a welding keyhole is
      developed. However, once the keyhole is formed, the reflected amount is as low as
      4-8%.

PMID- 21102708
TI  - Burst digital correlator as laser-Doppler velocimetry signal processor.
AB  - A burst digital correlator (BDC) has been developed to obtain flow-velocity
      information at high data rates from wideband laser-Doppler signals of low signal
      to-noise ratio (below 0 dB). Results with artificial signals show that, over a
      signal bandwidth of 5-120 MHz, the BDC has a measurement accuracy of less than
      0.4% at a maximum data rate (number of measurements per second) of 208 kHz when
      64 signal samples are correlated. The accuracy is better than 0.05% with a sample
      size of 512. The performance of the BDC was also evaluated in practical
      measurements of near-wall and strongly oscillatory recirculating flows.

PMID- 21102709
TI  - How different are the indicatrixes of the leaves of various woody plant species?
AB  - Some researchers assume that the light reflection from leaves is Lambertian, but
      I verify that some leaves exist showing no Lambertian reflection. One can measure
      the indicatrixes of leaves of various woody plant species by the use of a
      goniophotometer. Minnaert constants can be calculated from these indicatrixes for
      quantitative evaluation. I discuss why light scattering from leaves does not
      always obey Lambertian law.

PMID- 21102710
TI  - Transmission as an input boundary value for an analytical solution of a single
      scatter lidar equation.
AB  - Single-scatter lidar signals carry information on the spatial atmospheric
      backscatter coefficient, attenuated by the path-integrated extinction. Assuming
      that the relationship between the backscatter and the extinction is known, the
      inverted extinction profile and the path-integrated extinction are uniquely
      related to the input boundary value. The integrated extinction over a certain
      range interval is a measure of the optical transmission along that path. In
      reverse, for a given transmission over the path of interest, the input boundary
      value is uniquely defined. An analytical expression is derived that describes the
      input boundary condition for the inversion of the single-scatter lidar equation
      in terms of the transmission losses over the path of interest. The proposed
      method is useful in situations in which independent transmission measurements are
      carried out or in situations in which targets such as multiple cloud layers or
      beam stops are available in the lidar path. Equations for both the forward and
      the backward integration method are presented. Compared with the widely accepted
      inversion schemes that are based on single-point reference extinction values, the
      proposed method is less sensitive to noise.

PMID- 21102711
TI  - Effects of ocean waves on airborne lidar imaging.
AB  - The effects of ocean waves on lidar imaging of submerged objects are
      investigated. Two significant consequences of wave focusing or defocusing are
      quantified: (a) intensification of near-surface backscatter in which the mean
      return is increased relative to that for a flat interface, and (b) spatial
      temporal modulations of the backscattered return. For the former, mean returns
      can be as much as 50% larger than flat surface returns at shallow depth. For the
      latter, the strong modulations induced by wave motion present a dominant clutter
      field that significantly affects the imaging of shallow objects. Both effects are
      compensated at greater depths by beam spreading caused by multiple scattering,
      which diminishes the intensity of the wave focusing.

PMID- 21102712
TI  - Henyey-Greenstein and Mie phase functions in Monte Carlo radiative transfer
      computations.
AB  - Monte Carlo radiative transfer simulation of light scattering in planetary
      atmospheres is not a simple problem, especially the study of angular distribution
      of light intensity. Approximate phase functions such as Henyey-Greenstein,
      modified Henyey-Greenstein, or Legendre polynomial decomposition are often used
      to simulate the Mie phase function. An alternative solution using an exact
      calculation alleviates these approximations.

PMID- 21102713
TI  - Absolute real-time measurement of particle size distribution with the flying
      light-scattering indicatrix method.
AB  - The flying light-scattering indicatrix (FLSI, angular dependency of the intensity
      of light scattered by a moving individual particle) method, based on a scanning
      flow cytometer (SFC) that permits measurement of individual particle
      characteristics from light-scattering data, has been used for the determination
      of size distribution of the following particles: polystyrene latex, milk fat, and
      spores (Penicillium levitum, Aspergillus pseudoglaucus). The optical system of
      the SPC and empirical equations provided absolute sizing at the rate of 50
      particles/s. Size distributions obtained with the FLSI method and a best-fit
      procedure using Mie scattering theory have been compared.

PMID- 21102714
TI  - Approximations of polydispersed extinction.
AB  - A method to evaluate the polydispersed extinction efficiency rapidly is
      presented. The method can be used for any shape for which a monodisperse code or
      expression is known and any polydispersion for which a second moment inverse can
      be computed. Integration can be performed over any interval of the distribution
      function. Additionally, and if required, arbitrary accuracy can be obtained. This
      approach is applied to spheres and randomly oriented spheroids with nth-order log
      normal and modified gamma particle distributions.

PMID- 21102715
TI  - Light scattering by a multilayer sphere.
AB  - The recurrence algorithm for calculating electromagnetic scattering from a
      multilayer sphere, which was described recently by Wu and Wang [Radio Sci. 26,
      1393, (1991)], is derived in a slightly modified form and extended to include a
      calculation of the internal field and the absorption cross sections of the
      individual layers. The original algorithm calculates the scattering by a
      recurrence procedure that propagates the log derivatives of the Debye potentials
      outward from the core to the outer layer. The extended algorithm then continues
      the calculation by an inward recurrence procedure that propagates the Debye
      potentials from the outer layer to the core. Concurrent with the inward
      propagation, a separate algorithm calculates the absorption cross sections of the
      imbedded concentric spheres. The results of several example calculations are
      presented, including the differential cross section and internal electric field
      of a Luneburg lens.

PMID- 21102716
TI  - Optical technology in medicine and biology: Introduction.

PMID- 21102717
TI  - Spatially selective photocoagulation of biological tissues: feasibility study
      utilizing cryogen spray cooling.
AB  - Successful laser treatment of selected dermatoses such as hemangiomas requires
      thermally induced damage to blood vessels while protecting the epidermis. We
      present and test a procedure in a rabbit liver tissue model that utilizes cryogen
      spray cooling during continuous Nd:YAG laser irradiation to induce deep
      photocoagulation necrosis while protecting superficial tissues from thermal
      injury. Gross and histologic observations are consistent with calculated
      thicknesses of protected and photocoagulated tissues and demonstrate the
      feasibility of inducing spatially selective photocoagulation when cryogen spray
      cooling is used in conjunction with laser irradiation. This procedure may be
      useful in the thermal treatment of some pathological conditions for which it is
      desired that deep photocoagulation be induced while protecting superficial
      tissues.

PMID- 21102718
TI  - Optical properties of conjunctiva, sclera, and the ciliary body and their
      consequences for transscleral cyclophotocoagulation.
AB  - A number of recent studies have demonstrated the success of Nd:YAG and diode
      laser transscleral cyclophotocoagulation in the treatment of advanced glaucoma.
      Wavelength selection, however, has seldom been based on a clear understanding of
      the optical properties of tissues involved. The optical properties of
      conjunctiva, sclera, and the ciliary body adjacent to the limbus were
      investigated to find an optimal wavelength range for transscleral
      cyclophotocoagulation. The absorption and scattering coefficients of these layers
      were determined in the 300-1200-nm wavelength range by the use of a one
      dimensional inverse adding-doubling method. The measured optical properties of
      conjunctiva, sclera, and the ciliary body provide a basis for a comparative
      analysis of the laser wavelengths used clinically for transscleral
      cyclophotocoagulation.

PMID- 21102719
TI  - Combination of fiber-guided pulsed erbium and holmium laser radiation for tissue
      ablation under water.
AB  - Because of the high absorption of near-infrared laser radiation in biological
      tissue, erbium lasers and holmium lasers emitting at 3 and 2 um, respectively,
      have been proven to have optimal qualities for cutting or welding and coagulating
      tissue. To combine the advantages of both wavelengths, we realized a
      multiwavelength laser system by simultaneously guiding erbium and holmium laser
      radiation by means of a single zirconium fluoride (ZrF(4)) fiber. Laser-induced
      channel formation in water and poly(acrylamide) gel was investigated by the use
      of a time-resolved flash-photography setup, while pressure transients were
      recorded simultaneously with a needle hydrophone. The shapes and depths of vapor
      channels produced in water and in a submerged gel after single erbium and after
      combination erbium-holmium radiation delivered by means of a 400-um ZrF(4) fiber
      were measured. Transmission measurements were performed to determine the amount
      of pulse energy available for tissue ablation. The effects of laser wavelength
      and the delay time between pulses of different wavelengths on the photomechanical
      and photothermal responses of meniscal tissue were evaluated in vitro by the use
      of histology. It was observed that the use of a short (200-us, 100-mJ) holmium
      laser pulse as a prepulse to generate a vapor bubble through which the ablating
      erbium laser pulse can be transmitted (delay time, 100 us) increases the cutting
      depth in meniscus from 450 to 1120 um as compared with the depth following a
      single erbium pulse. The results indicate that a combination of erbium and
      holmium laser radiation precisely and efficiently cuts tissue under water with 20
      50-um collateral tissue damage.

PMID- 21102720
TI  - Optical profilometry of poly(methylmethacrylate) surfaces after reshaping with a
      scanning photorefractive keratectomy (SPRK) system.
AB  - A prototype frequency-quintupled Nd:YAG laser was used with a scanning system to
      create, on poly(methylmethacrylate) (PMMA) blocks, ablations corresponding to a
      correction of 6 diopters of myopia by photorefractive keratectomy. The topography
      of the ablated samples was measured with an optical profilometer to evaluate the
      smoothness and accuracy of the ablations. The ablation depth was larger than
      expected. With a 50% to 70% spot overlap, large valleylike variations with a
      maximum peak-to-peak amplitude of 20 um were observed. With an 80% spot overlap,
      the rms surface roughness was 1.3 um, and the central flattening was 7 diopters.
      This study shows that optical profilometry can be used to determine precisely the
      ablation per pulse and the smoothness and accuracy of surface ablations. Knowing
      the exact ablation per pulse is necessary to produce a smooth and accurate
      corneal surface by scanning photorefractive keratectomy.

PMID- 21102721
TI  - Drug delivery with microsecond laser pulses into gelatin.
AB  - Photo acoustic drug delivery is a technique for localized drug delivery by laser
      induced hydrodynamic pressure following cavitation bubble expansion and collapse.
      Photoacoustic drug delivery was investigated on gelatin-based thrombus models
      with planar and cylindrical geometries by use of one microsecond laser pulses.
      Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered
      colored oil into clear gelatin-based thrombus models. Cavitation bubble
      development and photoacoustic drug delivery were visualized with flash
      photography. This study demonstrated that cavitation is the governing mechanism
      for photoacoustic drug delivery, and the deepest penetration of colored oil in
      gels followed the bubble collapse. Spatial distribution measurements revealed
      that colored oil could be driven a few millimeters into the gels in both axial
      and radial directions, and the penetration was less than 500 um when the gelatin
      structure was not fractured.

PMID- 21102722
TI  - Measurement by laser Doppler interferometry of intraocular distances in humans
      and chicks with a precision of better than +/-20 um.
AB  - A laser Doppler interferometer was built for the precise measurement of
      intraocular optical distances in humans and chicks. A technique using Purkinje
      images was developed to position the chick's eye reproducibly. A computer
      algorithm for the objective analysis of the interference signal and determination
      of the optical distances is presented. The precision of this noncontact
      interferometric method for measuring the cornea-retina distance is better than +/
      20 um.

PMID- 21102723
TI  - Experimental validation of Monte Carlo and finite-element methods for the
      estimation of the optical path length in inhomogeneous tissue.
AB  - To validate models of light propagation in biological tissue, experiments to
      measure the mean time of flight have been carried out on several solid
      cylindrical layered phantoms. The optical properties of the inner cylinders of
      the phantoms were close to those of adult brain white matter, whereas a range of
      scattering or absorption coefficients was chosen for the outer layer.
      Experimental results for the mean optical path length have been compared with the
      predictions of both an exact Monte Carlo (MC) model and a diffusion equation,
      with two differing boundary conditions implemented in a finite-element method
      (PEM). The MC and experimental results are in good agreement despite poor
      statistics for large fiber spacings, whereas good agreement with the FEM
      prediction requires a careful choice of proper boundary conditions.

PMID- 21102724
TI  - Hyperbolic damped-wave models for transient light-pulse propagation in scattering
      media.
AB  - Transient optical transport in highly scattering media such as tissues is usually
      modeled as a diffusion process in which the energy flux is assumed proportional
      to the fluence (intensity averaged over all solid angles) gradients. Such models
      exhibit an infinite speed of propagation of the optical signal, and finite
      transmission values are predicted even at times smaller than those associated
      with the propagation of light. If the hyperbolic, or wave, nature of the complete
      transient radiative transfer equation is retained, the resulting models do not
      exhibit such drawbacks. Additionally, the hyperbolic equations converge to the
      solution at a faster rate, which makes them very attractive for numerical
      applications in time-resolved optical tomography.

PMID- 21102725
TI  - Depth determination of chromophores in human skin by pulsed photothermal
      radiometry.
AB  - We report on the application of pulsed photothermal radiometry (PPTR) to
      determine the depth of in-vitro and in-vivo subsurface chromophores in biological
      materials. Measurements provided by PPTR in combination with a nonnegative
      constrained conjugate-gradient algorithm are used to determine the initial
      temperature distribution in a biological material immediately following pulsed
      laser irradiation. Within the experimental error, chromophore depths (50-450 um)
      in 55 in-vitro collagen phantoms determined by PPTR and optical low-coherence
      reflectometry are equivalent. The depths of port-wine-stain blood vessels
      determined by PPTR correlate very well with their locations found by computer
      assisted microscopic observation of histologic sections. The mean blood-vessel
      depth deduced from PPTR and histologic observation is statistically
      indistinguishable (p > 0.94).

PMID- 21102726
TI  - Corneal-tissue absorption coefficients for 193- and 213-nm ultraviolet radiation.
AB  - The small-signal absorption coefficients of 193- and 213-nm nanosecond laser
      pulses in bovine corneal tissue have been studied. The absolute reflectance of a
      planar quartz-cornea interface was measured at various angles of incidence for
      low-intensity laser irradiation (i.e., pulse fluences 3 orders of magnitude below
      the ablation threshold). The reflectance-versus-angle data were analyzed by the
      use of Fresnel theory to estimate the effective complex index of refraction of
      the tissue. This analysis indicated corneal absorption coefficients of 39,900 +/-
      9800 cm(-1) at 193 nm and 21,400 +/- 4900 cm(-1) at 213 nm.

PMID- 21102727
TI  - Dynamic 193-nm optical properties of water.
AB  - Previous assumptions that water is not a 193-nm chromophore during ArF excimer
      laser tissue ablation are based on room-temperature data and ignore spectroscopic
      literature that suggests a strong temperature dependence of far-ultraviolet water
      absorption. By the use of a Q-switched Er:YAG laser as a pump source and an ArF
      excimer laser as a probe source, thermal generation and relaxation of 193-nm
      water absorption were characterized under nonequilibrium high-temperature and
      high-pressure conditions. At volumetric energy densities as small as 2 kJ/cm(3)
      relative to room temperature, the 193-nm absorption coefficient of water was
      measured to increase by more than 5 orders of magnitude. These results are
      consistent with the hypothesis that the absorption of 193-nm radiation by water
      may play a role in ArF excimer laser ablation of tissue.

PMID- 21102728
TI  - Determination of the scattering coefficient and the anisotropy factor from laser
      Doppler spectra of liquids including blood.
AB  - Laser Doppler measurements were performed on scattering liquids flowing through a
      highly scattering static medium to determine the scattering coefficient and the
      anisotropy factor of the liquids. Monte Carlo simulations of light propagation in
      the static and moving media were used to calculate the Doppler spectra for
      suspensions of polystyrene spheres in water, and these spectra were in excellent
      agreement with experimental results. A faster Monte Carlo code was developed so
      that nonlinear regressions to the measured laser Doppler spectra could be used to
      determine the anisotropy factor of other liquids. This approach was used to
      deduce the scattering properties of Intralipid and blood at lambda = 820 nm. It
      was found that the anisotropy factor of blood is well described by Mie theory in
      contradiction to results reported in the literature that were obtained by
      goniometric measurement of the phase function.

PMID- 21102729
TI  - Dynamics of tissue optics during laser heating of turbid media.
AB  - The dynamics of the optical behavior of tissue during the photothermal
      interaction of laser radiation with tissue could significantly affect the
      optimization of light doses for effective and safe applications of lasers in
      medicine. Characterization of the dynamics of tissue optics during laser heating
      was performed by means of simultaneous measurements of the total transmittance,
      diffuse reflectance, and surface temperature of fresh and thermally coagulated
      human skin and canine aorta during long-pulsed Nd:YAG laser heating with a double
      integrating-sphere system and an infrared camera. Thermally induced changes in
      the optical properties of tissue caused a decrease in the total transmittance and
      an increase in the diffuse reflectance of both fresh and precoagulated skin and
      aorta samples. For fresh tissue, these changes were primarily reversible until
      photocoagulation occurred, then both the reversible, as well as the irreversible,
      changes were observed. However, for precoagulated tissue the reversible changes
      in the optical properties were dominant, whereas the irreversible changes were
      insignificant. Results from this study indicate the existence of the nonlinear
      behavior in the optics of turbid biological media during pulsed laser heating.
      Possible mechanisms responsible for this nonlinear optical behavior are
      discussed.

PMID- 21102730
TI  - Fiber-optic evanescent-wave spectroscopy for fast multicomponent analysis of
      human blood.
AB  - A spectral analysis of human blood serum was undertaken by fiber-optic evanescent
      wave spectroscopy (FEWS) by the use of a Fourier-transform infrared spectrometer.
      A special cell for the FEWS measurements was designed and built that incorporates
      an IR-transmitting silver halide fiber and a means for introducing the blood
      serum sample. Further improvements in analysis were obtained by the adoption of
      multivariate calibration techniques that are already used in clinical chemistry.
      The partial least-squares algorithm was used to calculate the concentrations of
      cholesterol, total protein, urea, and uric acid in human blood serum. The
      estimated prediction errors obtained (in percent from the average value) were 6%
      for total protein, 15% for cholesterol, 30% for urea, and 30% for uric acid.
      These results were compared with another independent prediction method that used
      a neural-network model. This model yielded estimated prediction errors of 8.8%
      for total protein, 25% for cholesterol, and 21% for uric acid.

PMID- 21102731
TI  - Capillary waveguide optrodes: an approach to optical sensing in medical
      diagnostics.
AB  - Glass capillaries with a chemically sensitive coating on the inner surface are
      used as optical sensors for medical diagnostics. A capillary simultaneously
      serves as a sample compartment, a sensor element, and an inhomogeneous optical
      waveguide. Various detection schemes based on absorption, fluorescence intensity,
      or fluorescence lifetime are described. In absorption-based capillary waveguide
      optrodes the absorption in the sensor layer is analyte dependent; hence light
      transmission along the inhomogeneous waveguiding structure formed by the
      capillary wall and the sensing layer is a function of the analyte concentration.
      Similarly, in fluorescence-based capillary optrodes the fluorescence intensity or
      the fluorescence lifetime of an indicator dye fixed in the sensing layer is
      analyte dependent; thus the specific property of fluorescent light excited in the
      sensing layer and thereafter guided along the inhomogeneous waveguiding structure
      is a function of the analyte concentration. Both schemes are experimentally
      demonstrated, one with carbon dioxide as the analyte and the other one with
      oxygen. The device combines optical sensors with the standard glass capillaries
      usually applied to gather blood drops from fingertips, to yield a versatile
      diagnostic instrument, integrating the sample compartment, the optical sensor,
      and the light-collecting optics into a single piece. This ensures enhanced sensor
      performance as well as improved handling compared with other sensors.

PMID- 21102732
TI  - Time-gated viewing studies on tissuelike phantoms.
AB  - A time-gated technique to enhance viewing through highly scattering media such as
      tissue is discussed. Experiments have been performed on tissuelike plastic
      phantoms to determine the possibilities and limitations of the technique. The
      effects of the time-gate width and the localization, size, and optical properties
      of hidden objects have been studied. A computer model to simulate light
      propagation in tissue is also presented. The predictions of the model are
      compared with experimental results.

PMID- 21102733
TI  - Sources of contrast in confocal reflectance imaging.
AB  - The relationship between optical properties and image contrast in confocal
      imaging is investigated. A Monte Carlo simulation has been developed to analyze
      the effects of changes in scattering, index of refraction, and absorption in a
      three-layer medium. Contrast was calculated from the computed signal-to
      background ratios for changes in tissue optical properties. Results show that the
      largest source of contrast is changes in refractive index.

PMID- 21102734
TI  - Enhanced frequency-domain optical image reconstruction in tissues through total
      variation minimization.
AB  - Optical image reconstruction in heterogeneous turbid media is sensitive to noise,
      especially when the signal-to-noise ratio of a measurement system is low. A total
      variation-minimization-based iterative algorithm is described in this paper that
      enhances the quality of reconstructed images with frequency-domain data over that
      obtained previously with a regularized least-squares approach. Simulation
      experiments in an 8.6-cm-diameter circular heterogeneous region with low- and
      high-contrast levels between the target and the background show that the quality
      of the reconstructed images can be improved considerably when total-variation
      minimization is included. These simulated results are further verified and
      confirmed by images reconstructed from experimental data by the use of the same
      geometry and optically tissue-equivalent phantoms. Measures of imaging
      performance, including the location, size, and shape of the reconstructed
      heterogeneity, along with absolute errors in the predicted optical-property
      values are used to quantify the enhancements afforded by this new approach to
      optical image reconstruction with diffuse light. The results show improvements of
      up to 5 mm in terms of geometric information and an order of magnitude or more
      decrease in the absolute errors in the reconstructed optical-property values for
      the test cases examined.

PMID- 21102735
TI  - Parabolic mirror optics for collimation of a crescent blue laser beam radiated
      from channel waveguide Cerenkov second-harmonic generation.
AB  - Parabolic mirror optics to collimate the crescent-shaped blue laser beam that
      radiates from Cerenkov second-harmonic generation (SHG) in a channel waveguide
      configuration is proposed. Mirror collimation optics has a large tolerance to the
      variations of SHG element parameters, such as the laser source wavelength, as
      well as to mirror displacement. The anisotropy of a nonlinear crystal in which
      the waveguide is fabricated has been taken into account. The optimum mirror
      alignment to obtain a collimated blue laser beam is evaluated in terms of
      Marechal's criterion. The minimum wave-front aberration with beam intensity
      weighted is 0.054 lambdaSH. The convergence of the collimated beam is less than
      1.6 mrad, and, by using an objective lens, the collimated beam can be focused to
      a diameter of less than 1 um, which is 1.27 times the diffraction-limited
      focusing point.

PMID- 21102736
TI  - Precision crystal corner cube arrays for optical gratings formed by (100) silicon
      planes with selective epitaxial growth.
AB  - High-quality, micrometer scale, corner cube arrays were grown on (111) silicon
      substrates by selective epitaxial growth (SEG) techniques. Sixteen different
      arrays were produced that had periodic corner spacing ranging from 3 to 50 um.
      The arrays were formed by suppressing silicon SEG in a regular geometric pattern,
      producing the three mutually perpendicular (100) smooth crystal planes. For
      coherent light of 633-nm wavelengtha sharp diffraction pattern of threefold
      symmetry was observed out to 7 maxima, as well as a retroreflection component.

PMID- 21102737
TI  - Determination of the conversion gain and the accuracy of its measurement for
      detector elements and arrays.
AB  - Standard statistical theory is used to calculate how the accuracy of a conversion
      gain measurement depends on the number of samples. During the development of a
      theoretical basis for this calculation, a model is developed that predicts how
      the noise levels from different elements of an ideal detector array are
      distributed. The model can also be used to determine what dependence the accuracy
      of measured noise has on the size of the sample. These features have been
      confirmed by experiment, thus enhancing the credibility of the method for
      calculating the uncertainty of a measured conversion gain.

PMID- 21102738
TI  - Light-reflecting concentrators for photomultipliers with curved photocathodes.
AB  - Three-dimensional (3D) concentrators for photomultipliers with curved
      photocathodes have been designed by taking the figures of revolution of ideal two
      dimensional (2D) concentrators that are constructed from the 2D profiles of the
      photocathodes. Two new arguments are presented as to why these 3D concentrators
      cannot quite reach the maximum concentration factor allowed by the conservation
      of phase space. Improvements in performance have been obtained by optimizing the
      collection of off-axis rays and filling the concentrator with a dielectric of
      suitable refractive index. The complicated optical behavior of the photocathode
      does not affect concentrator performance.

PMID- 21102740
TI  - Graded-index profiles by inversion with Lloyd's mirage.
AB  - A method is presented for calculating graded-index profiles from phase
      information obtained with the help of the recently proposed Lloyd's mirage
      experiment. It is based on an exact solution of the inverse scattering problem in
      the ray (WKB) approximation. An analytical example is given for illustration.

PMID- 21102739
TI  - Modal approximation for the electromagnetic field of a near-field optical probe.
AB  - A formalism is given in which the optical field generated by a near-field optical
      aperture is described as an analytic expansion over a complete set of optical
      modes. This vectoral solution preserves the divergent behavior of the near field
      and the dipolar nature of the far field. Numerical calculation of the fields
      requires only evaluation of a well behaved, one-dimensional integral. The
      formalism is directly applicable to experiments in near-field scanning optical
      microscopy when relatively flat samples are evaluated.

PMID- 21102741
TI  - Fiber-optic extrinsic Fabry-Perot vibration-isolated interferometer for use in
      absolute gravity meters.
AB  - In an absolute gravity meter, a laser interferometer measures the position of a
      test mass that is falling ina vacuum. The calculated value of gravity is the
      average acceleration of the mass during a set ofdrops. Since systematic
      accelerations of the optical system will bias the measured value of
      gravity,various interferometer geometries have been implemented in the past to
      isolate the optical system fromground motion. We have developed and tested a low
      finesse fiber-optic extrinsic Fabry-Perotinterferometer that is fixed to the mass
      of a critically damped seismometer in which the effects ofsystematic ground
      motion and acoustic vibrations are reduced.

PMID- 21102742
TI  - Robust phase-unwrapping method for phase images with high noise content.
AB  - We present a robust method of phase unwrapping that was designed for use on noisy
      phase images with arbitrary fringe patterns. The method proceeds by first
      identifying distinct regions between fringe boundaries in an image and then phase
      shifting the regions with respect to one another by multiples of 2pi to unwrap
      the phase. Image pixels are segmented between interfringe and fringe boundary
      areas by fitting a plane model using least squares to overlapping domains
      centered on all pixels. The method is tolerant of fringe gradient degradation
      caused by noise, filtering artifacts, and finite instrumentation bandwidth.

PMID- 21102743
TI  - Camera influence on the phase-measurement accuracy of a phase-shifting speckle
      interferometer.
AB  - In a real phase-shifting interferometer the camera (i.e., a photodetector plus an
      analog-to-digital converter) cuts off intensities above some saturation level and
      provides a limited number of digitization steps. Owing to the intensity
      statistics of speckle fields, this might severely influence the accuracy of the
      calculated speckle phase. The optimum beam ratio and the modulation of the camera
      are computed. To calculate the standard deviation of the phase difference, first,
      we derive a relation that shows that the variances of the two measured phase
      frames are equal and that they must be added with the decorrelation-dependent
      variance. To obtain the minimum phase-measurement error of 25.1 mrad, it is found
      that the mean speckle intensity ought to be adjusted to be 0.058 times the
      saturation intensity of the camera and that the beam ratio is to be 5.7. The
      results are confirmed by computer simulation of a two-wavelength speckle
      interferometer.

PMID- 21102744
TI  - Dual-wavelength heterodyne differential interferometer for high-precision
      measurements of reflective aspherical surfaces and step heights.
AB  - A dual-wavelength heterodyne differential interferometer was developed and tested
      together with scanning mechanics. To extend the range of unambiguity, two
      wavelengths were applied. This is important for measuring structures with surface
      discontinuities (reliefs, steps). The automatic adjustment of the interferometer
      with respect to the rotational symmetrical measuring surfaces (aspheres) is
      important. An adjustment is needed to scan the asphere through its vertex.
      Typical measurements on a sphere, an asphere, and steps are shown.

PMID- 21102745
TI  - Self-pumped phase-conjugate interferometer with a photorefractive iron-doped
      lithium-niobate crystal.
AB  - A single object wave is amplitude divided by a beam splitter into two waves of
      equal intensity that are made to interfere at the back surface of an iron-doped
      lithium-niobate crystal so that the normal to the back surface is the angular
      bisector of the input waves. The interference results in the formation of a phase
      grating (Bragg grating) in the volume of the crystal. These waves are diffracted
      at the Bragg grating on both the front focal plane and the back focal plane of
      the crystal. The wave diffracted in the back focal plane from the Bragg grating
      and counterpropagating to the incident wave is observed to be the phase conjugate
      of the input object wave. The wave diffracted in the front focal plane of the
      Bragg grating is incorporated into the design of an interferometer to measure a
      specific in-plane displacement of the object wave. It is theoretically evaluated
      and experimentally demonstrated that interferometers such as those that
      incorporate conjugate-wave pairs are highly sensitive.

PMID- 21102746
TI  - Experimental verification of a theory of the influence of measurement conditions
      on temperature measurement accuracy with IR systems.
AB  - A theory of the influence of measurement conditions on temperature measurement
      accuracy with infrared systems has been recently presented. A comparison study of
      the shortwave (3-5-um) and longwave (8-12-um) measuring IR cameras was conducted
      on the basis of this theory. The results of the simulations show that the
      shortwave systems in typical measurement conditions generally offer better
      accuracy in temperature measurement than do the longwave systems. Some
      experiments that use a commercially available IR camera were carried out to
      verify the theory. The results of these experiments and a discussion about the
      theory limitations are presented.

PMID- 21102747
TI  - Improved solution for the cemented doublet.
AB  - A method is described that permits the calculation of a cemented doublet with a
      given spherical aberration and coma at the edge of the lens. In particular the
      aberrations can be set to zero. Given one glass, the equations reported in this
      paper permit the determination of a second matching glass that minimizes the
      spherochromatism and coma of the lens. This result is obtained by the
      introduction, into the third-order thin-lens formulas, the third-order values of
      the aberration coefficients, as derived from the equation developed by Mossotti
      which yields zero finite aberrations for the same lens with added thickness.
      After a brief historical introduction, the third-order equations are developed
      and tables for the color-correcting glasses and SI and SII (the Seidel third
      order coefficients) are given for objects at infinity and at a magnification of -
      1, both for flint- and crown-leading cases. The paper closes with a table of
      corrected doublets.

PMID- 21102748
TI  - Inclined toroidal surface that fits an off-axis conic section.
AB  - We developed a formulation using the continuous least-squares method to determine
      the inclined toroidal surface that best fits a given off-axis conic section. A
      toroid with a known curvature is used to obtain an analytic equation for the
      angle of inclination of the axis with respect to the normal to the center of the
      off-axis section.

PMID- 21102749
TI  - Optical, thermo-optic, electro-optic, and photoelastic properties of bismuth
      germanate (Bi(4)Ge(3)O(12)).
AB  - To assess the suitability of bismuth germanate as an electro-optic material for
      high precision applications, we have confirmed and extended previous data on its
      refractive index, electro-optic tensor element r(41), and thermal expansion
      coefficient. In addition, we have measured the thermo-optic coefficient dn/dT,
      the temperature dependence of the electro-optic coefficient, and the stress-optic
      tensor elements. From the stress-optic tensor elements and previously published
      data, we have computed the strain-optic tensor elements. The index of refraction
      is given, to a good approximation, by the single-term Sellmeier equation, n(2) -
      1 = S(0)lambda(0)(2)/[1 - (lambda(0)/lambda)(2)], with S(0) = 95.608 um(-2) and
      lambda(0) = 0.1807 um. The thermo-optic coefficient is 3.9 * 10(-5)/ degrees C at
      632.8 nm and 3.5 * 10(-5)/ degrees C at 1152.3 nm. The electro-optic tensor
      element varies between approximately 1.05 and 1.11 pm/V over the spectral range
      of 550-1000 nm; its normalized effective change with temperature is approximately
      1.54 * 10(-4)/ degrees C. The thermal expansion coefficient is 6.3 * 10(-6)/
      degrees C over the range 15-125  degrees C. Values of the stress-optic tensor
      elements are q(11) - q(12) = -2.995 * 10(-13) m(2)/N and q(44) = -0.1365 * 10(
      12) m(2)/N. The strain-optic tensor elements are p(11) - p(12) = -0.0266 and
      p(44) = -0.0595.

PMID- 21102750
TI  - Polarization of specular reflection and near-specular scattering by a rough
      surface.
AB  - Polarization of specular reflection and near-specular scattering (NSS) by a
      randomly rough surface is investigated by the use of a Mueller matrix
      formulation. The collective effect by a rough surface on the average specular
      field results in reflectance loss and polarization, which can be explained by an
      effective medium theory. Effects of random NSS can be represented by a scattering
      matrix that is partially coherent and polarized. The incoherent and unpolarized
      part of scattering causes depolarization, and the coherent and polarized parts of
      scattering change the apparent polarization properties of specular reflection.
      Results of a simulation and least-squares fit of ellipsometric data to the models
      including the NSS effect, for a black anodized aluminum sample, are presented.
      Simultaneous least-squares fits for both ellipsometric data and reflectance data
      at multiple angles of incidence at three different wavelengths gave approximately
      the same rms roughness, which agrees with the profilometric values reported
      previously.

PMID- 21102751
TI  - Emission polarization of roughened glass and aluminum surfaces.
AB  - Ellipsometer measurements of the effective complex refractive index at a
      wavelength of 10.6 MUm are made on a series of glass and aluminum surfaces of
      increasing surface roughness. The measured values are then used to calculate the
      degree of emission polarization and are shown to be in agreement with the
      experimentally determined values when depolarization is small. Comparisons are
      also made with calculations based on the Kirchhoff scattering theory. Both the
      theory and the experimental results indicate that it is the local surface slope
      and not the roughness magnitude that is the prime factor in determining the
      degree of emission polarization from the samples studied.

PMID- 21102752
TI  - Polarization characterization of a Mach-Zehnder interferometer.
AB  - Polarization characterization of a Mach-Zehnder interferometer, based on the
      state of polarization (SOP) and power measurement at the interferometer output,
      is presented. We study the SOP and degree of polarization (DOP) of the output
      light, first as a function of the light power in each arm of the interferometer
      for a fixed input SOP and DOP, and second as a function of the SOP's in each arm
      of the interferometer for a fixed input power. Stokes formalism and the Poincare
      sphere are used for simultaneous representation of the SOP and DOP, as well as
      their evolution. It is shown that the SOP and DOP stability and also the output
      light power are highly dependent on the light source coherence. Knowledge of
      these different parameters leads to configurations that allow simultaneous
      control of the SOP and DOP. We can hence realize a quasi-monochromatic
      nonpolarized light source, which is useful for the polarization-independent
      characterization of optical components.

PMID- 21102753
TI  - Effects of non-Lambertian surfaces on integrating sphere measurements.
AB  - The effects of non-Lambertian scattering of the interior wall of an integrating
      sphere are examined through a sphere simulation model. The model employs Monte
      Carlo techniques. A sphere used for measurement of directional-hemispherical
      reflectance is modeled. The simulation allows sphere wall scattering to vary from
      perfectly Lambertian to perfectly specular in steps. The results demonstrate that
      significant measurement error can result as the scattering deviates from the
      Lambertian ideal. The error is found to be a strong function of the wall
      reflectance value as well: it is minimized for reflectances approaching 1.0 and
      increases as the reflectance value decreases to the minimum value examined of
      0.5. The magnitudes of the errors associated with non-Lambertian scattering are
      also shown to be relatively independent of the specific field of view of the
      detector used in the measurement.

PMID- 21102754
TI  - Development of improved electrical-substitution radiometers at the National
      Research Council of Canada.
AB  - We describe the development of a third generation of electrical-substitution
      radiometers (ESR's) at the National Research Council of Canada. The new ESR's
      follow the same general design as before, but incorporate improved thermopiles
      and electrical heating elements. The ESR's have a responsivity between 0.6 and
      1.0 VW(-1), a time constant of approximately 2.0 s, a uniformity of 0.1% over a 6
      mm-diameter region, and a noise level of approximately 6 nW. Performance
      characteristics of the new ESR's are discussed. It is shown that calibrations
      performed with these ESR's agree with those made with the previous generation of
      ESR's to better than 0.05%.

PMID- 21102755
TI  - Numerical and experimental study of disordered multilayers for broadband x-ray
      reflection.
AB  - The effect of layer thickness disorder in periodic multilayers on x-ray
      reflectivity is investigated numerically and experimentally. We present ensemble
      calculations, taking into account absorption and interfacial roughness. It is
      demonstrated that layer thickness disorder yields band broadening and increased
      integrated reflectivity For applications we concentrate on extrema of the
      ensembles, giving the highest integrated reflectivity We develop global
      optimization methods that can also be used to generate specified reflection band
      structures. In a few examples, applications of the optimization methods are
      discussed. To illustrate the practical applicability of the methods, we compare
      experimental realizations to the calculation. In one case we achieve a 42%
      increase in integrated reflectivity in the 130 A < lambda < 190 A spectral range
      with respect to a periodic multilayer with its first-order Bragg peak in the
      center of that range. Accurate control of layer thicknesses is our main
      experimental obstacle.

PMID- 21102756
TI  - Effects of bombardment on optical properties during the deposition of silicon
      nitride by reactive ion-beam sputtering.
AB  - Thin silicon nitride (Si(1_x)N(x)) films were synthesized without substrate
      heating by means of reactive argon-ion sputtering of either silicon or a silicon
      nitride target in the 1000-1500-eV energy range at a nitrogen partial pressure of
      1.3 * 10(-2) Pa and with simultaneous nitrogen ion-assisted bombardment in the
      300-500-eV low energy range. The extinction coefficient and refractive index of
      the films were directly dependent on the N(+) ion-to-atom arrival ratio, assisted
      ion energy, film growth rate, and indicated a correlation with film stoichiometry
      and disorder. Si(3)N(4) films were obtained for N(+) ion/Si atom arrival ratios
      from 0.6 to 1.7 and for different Si:N atom arrival rates and had a refractive
      index as high as 2.04 (633 nm) and a low hydrogen content as indicated by IR
      spectra.

PMID- 21102757
TI  - Prefocusing optics for soft-x-ray synchrotron-radiation monochromators.
AB  - We present a mirror system to be used for the prefocusing optics of soft-x-ray
      monochromators using synchrotron radiation from a bending magnet source. The
      system consists of a cylindrical and a toroidal mirror arranged coplanarly. It
      can be made, by proper selection of the curvature radii of the mirrors, free of
      astigmatic coma. The design method is described in detail; the system is
      evaluated by exact ray-tracing calculations. Also given is a design example of
      the prefocusing optics in a soft-x-ray synchrotron radiation be aniline.

PMID- 21102758
TI  - Integrated diffractive andrefractive elements for spectrum shaping.
AB  - Diffractive elements can be designed for spectrum shaping in the Fourier or
      Fresnel plane by iterative methods. It is necessary to use a Fourier lens and the
      wavelength for which the diffractive elements were designed to get the required
      spectrum shaping at the Fourier plane. Using a different wavelength will cause
      chromatic aberration. We deal with the combination of refractive and diffractive
      elements and two or more different diffractive elements on the same element to
      get appropriate beam shaping of light sources with a multiple spectral output.
      Simulations are preformed that transform the profile of a He-Ne laser with a
      Nd:YAG laser source, and shape the trapezoidal beam profile of an excimer laser
      into a Gaussian beam is also considered.

PMID- 21102759
TI  - Adaptive optics and ground-to-space laser communications.
AB  - The relationships between laser communication system parameters and adaptive
      optics system parameters are addressed. Improvement in optical signal propagation
      between space-based receivers and ground-based transmitters is possible with
      adaptive optics systems that compensate for a few degrees of freedom. Beginning
      with the relationship between optical signal fade and surge and the atmospheric
      log-amplitude variance and coupling to expressions that combine adaptive optics
      systems performance with the reduction in log-amplitude variance, system level
      examinations of the effects of adaptive optics can be done. Examples are given
      that show the advantageous reduction in signal fade and surge when adaptive
      optics are built into the optical system.

PMID- 21102760
TI  - Phase measurement and compensation of a wave front using a twisted nematic liquid
      crystal television.
AB  - A twisted nematic liquid-crystal television (LCTV) has been used together with
      Twyman?"Green type interferometers to measure and compensate the phase distortion
      of a wave front. The twisted nematic LCTV has been operated as a phase-only
      modulator, and its phase retardation ability has been doubled in these
      experiments. The phase function of a phase object has been measured in different
      arrangements of the experimental setup.

PMID- 21102761
TI  - Holographic gratings for the Far Ultraviolet Spectroscopic Explorer: development,
      imaging, and efficiency tests of two prototypes.
AB  - We report on a study and test of two 6000-groove/mm prototype holographic
      gratings for NASA's FarUltraviolet Spectroscopic Explorer (FUSE) mission. The
      first grating was designed and developed onthe basis of the FUSE requirements as
      specified at the end of the first study in 1992. This design relieson an
      ellipsoidal grating, recorded with aberrated wave fronts to correct sagittal
      coma. The secondgrating corresponds to the new design adopted after the complete
      mission was restructured in1993. With this solution a new family of spherical
      holographic gratings recorded with stigmaticsources was permitted to increase the
      aperture size while simplifying the figuring and recording of theblank. The
      design, fabrication, and testing of each prototype are described, and we show
      that thechallenging requirement of a 30,000 resolving power at 1000 A, with a 25%
      groove efficiency, is reached.

PMID- 21102762
TI  - Binary gratings for CO(2) laser-beam diagnostics.
AB  - Properties of binary gratings for beam diagnostics of high-power CO(2) lasers are
      investigated. The layout uses a modal theory that includes absorption of metallic
      surfaces by an impedance boundary condition. Radiation-resistant gratings were
      fabricated in copper with photolithography combined with galvanic technology. In
      this way gratings have been realized in which the first-order diffraction
      efficiencies are polarization independent. Use of a second grating to reduce
      elliptical beam distortion is demonstrated. Finally it is shown that Rayleigh
      anomalies for binary diagnostic gratings are accompanied by high absorption.

PMID- 21102763
TI  - Optical diffusion imaging: a comparative numerical and experimental study.
AB  - We present a low-cost photodiode-LED apparatus for making broadband frequency
      domain photon migration measurements. We compare measured data to finite
      difference frequency domain solutions of the diffusion approximation of the
      Boltzmann transport equation. Specific comparisons include the influence of
      boundary conditions on simulations and the effect of finite source size on
      resolution.

PMID- 21102764
TI  - Electroless silver as an optical coating in an operational environment.
AB  - Long-term, independent experiments show a high degradation rate and short
      lifetime for electroless silver as a mirror coating operating at visible
      wavelengths in an observatory environment. Acid formed by water vapor mixing with
      sulfur in volcanic dust diffuses through pinholes in the coating generated during
      deposition. This causes internal corrosion and delamination after only 3-4
      months. In addition, a layer of silver sulfide results in tarnish, which reduces
      reflectance. Rates of sulfidation and internal corrosion are shown to depend on
      the concentration of sulfur and the exposure rate. Comparisons of performance,
      lifetime, and the application process are made with bare aluminum and two
      variations of enhanced silver.

PMID- 21102765
TI  - Speckle noise in laser bar-code-scanner systems.
AB  - We present a theoretical model and its experimental verification for speckle
      induced noise in laser-based bar-code-scanner systems. We measured the dependence
      of the signal-to-speckle-noise ratio on distance, spot size, and detector size.
      Analyses of the power spectra of both the speckle noise and of the measured
      surface profiles of different substrates suggest that the paper surface
      granularity can be approximated by a white Gaussian noise process, thus
      confirming the assumption of the theoretical model.

PMID- 21102766
TI  - Measurement of plant movement in young and mature plants using electronic speckle
      pattern interferometry.
AB  - The use of electronic speckle pattern interferometry (ESPI) to monitor and
      measure the surface movement of plants is presented. We chose to study the
      gravitropical response of a coleoptile (the shoot from a growing seed) to
      illustrate the potentials of the technique for botanical measurements. A
      coleoptile represents a very fast growing translucent biological object, a
      difficult object to record interferometrically Traditional holographic
      interferometry is not suited to the study of objects with such rapid fringe
      decorrelation. However, ESPI with its short exposure time, fast sampling rate,
      and high sensitivity makes it possible to obtain fringes even on the very tip of
      the coleoptile where the microstructure changes most rapidly.

PMID- 21102767
TI  - Image properties of polycrystalline storage films.
AB  - Polycrystalline storage films are applied in various fields of x-ray radiography.
      Depending on the application, different requirements exist for the sensitivity
      and spatial resolution of the film, and these are related to light scattering in
      the film. Scattering is controlled by optical properties of the storage medium,
      e.g., the scattering length by the grain size, the absorbance by the choice of
      the binder, and the geometric boundary conditions by the film thickness. A method
      treating the scattering of light as a diffusionlike process is presented. The
      sensitivity, resolution, and other image properties are determined from the
      optical properties. The influence of the scattering length, absorbance, and
      thickness on image parameters is calculated and discussed. The results indicate
      that optimizing the image properties of the film can be achieved by a reduction
      of the absorbance and an increase in film thickness to the penetration depth of
      the x rays. Furthermore, it is shown that the resolution of the film can be set
      strictly according to the requirements of an individual application if the
      scattering length in the medium is adjusted.

PMID- 21102768
TI  - Refractive index of NH(4)Cl-H2O as a function of wavelength: the effect of
      temperature and concentration.
AB  - The refractive index of NH(4)Cl-H(2)O solutions has been measured over a
      wavelength range from 496.5 to 690 nm. The NH(4)Cl concentration was varied from
      15 to 30 wt. % over a temperature range from 10 to 35  degrees C. We obtained
      mathematical equations relating the refractive index to wavelength, temperature,
      and concentration using the least-squares method. A knowledge of these properties
      is important for analyzing and modeling the dendritic growth of this system.

PMID- 21102769
TI  - Secondary-phase-modulation method for open-loop fiber-optic gyroscopes.
AB  - A proposed method of secondary phase modulation for open-loop fiber-optic
      gyroscopes is examined in general terms. To detect the rotation rate of a system
      through a beat-frequency channel, we employ linearly combined signals with
      different frequencies for the optical phase modulation. We find that the proper
      combinations of the modulation frequencies can optimize the sensitivity of
      gyroscopes. With this method we can employ a high-frequency band for optical
      phase modulations while keeping relative a lower-frequency band of the detection
      channel. The theoretically derived result is experimentally confirmed by using a
      lithium-niobate (LiNbO(3)) optical phase modulator. We also discuss the
      combination setup with an optical integrated-circuit device and digital signal
      processing.

PMID- 21102770
TI  - Light scattering by ellipsoids in a physical optics approximation.
AB  - A physical optics approximation based on Presnel's laws is developed to calculate
      the intensity of light scattered by a three-axis ellipsoid of any orientation and
      any refractive index. Some results concerning totally reflecting spheres and
      dielectric spheroids are presented. An approach suitable for large scatterers is
      particularly good for small scattering angles. The angular intensities, i(1) and
      i(2), are then plotted versus theta for large axially oriented ellipsoids of
      various thicknesses. Theoretical small-angle light-scattering patterns are also
      presented and discussed. The data from one of them correspond to red cells in a
      shear flow.

PMID- 21102771
TI  - Discrete-dipole-approximation-based light-scattering calculations for particles
      with a real refractive index smaller than unity.
AB  - To assess the efficiency and accuracy of light-scattering calculations based on
      the discrete dipole approximation (DDA) for particles with a real relative
      refractive index smaller than unity, differential scattering cross sections and
      scattering efficiency factors were calculated for spherical particles. We
      performed the calculations for oxide particles and voids embedded in glass and
      silicon, using the exact scattering theory (Mie scattering) and the DDA. A
      comparison of the results shows that the DDA is applicable in the above
      refractive-index regime, and the conditions under which DDA-based calculations
      can provide scattering data with good accuracy are discussed.

PMID- 21102772
TI  - Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid
      media: analytic solutions and applications.
AB  - We present analytic solutions for fluorescent diffuse photon density waves
      originating from fluorophores distributed in thick turbid media. Solutions are
      derived for a homogeneous turbid medium containing a uniform distribution of
      fluorophores and for a system that is homogeneous except for the presence of a
      single spherical inhomogeneity Generally the inhomogeneity has fluorophore
      concentration, and lifetime and optical properties that differ from those of the
      background. The analytic solutions are verified by numerical calculations and are
      used to determine the fluorophore lifetime and concentration changes required for
      the accurate detection of inhomogeneities in biologically relevant systems. The
      relative sensitivities of absorption and fluorescence methods are compared.

PMID- 21102773
TI  - Effect of diffraction on early-arriving photons during femtosecond laser
      transillumination of highly scattering media of biological significance.
AB  - Early-arriving photons of 100-fs laser pulses transmitted through highly
      scattering media have been detected by a streak camera. Because of their partial
      spatial coherence, they are affected by diffraction from small hidden
      discontinuities. The experimental data of the patterns are analyzed with Fresnel
      diffraction theory and then corrected accordingly. Submillimeter hidden objects
      were scanned and imaged. Diffraction correction resulted in a significantly
      improved contrast in the hidden object's image.

PMID- 21102774
TI  - Dynamic light scattering from small particles: expected accuracy in hemoglobin
      data reduction.
AB  - Dynamic light scattering from protein solutions can be applied to the detection
      of conformational changes and to the measurement of particle size. Because
      accurate results can be adversely affected by experimental perturbations, careful
      procedures are necessary both in data acquisition and in data analysis.
      Autocorrelation functions (ACF?s) of scattered light are simulated here to
      evaluate the role of the perturbations affecting measured signals from dilute
      protein solutions. The analysis of measured and simulated ACF?s has been
      performed both by cumulant expansion and by a nonlinear least-squares fit,
      thereby allowing the definition of criteria for the optimization of the fitting
      parameters and of the measuring conditions. Moreover, by comparing experimental
      data from hemoglobin solutions and computer simulations, we show how to evaluate
      the contributions of polydispersity and statistical noise affecting the
      measurements.

PMID- 21102775
TI  - Noise-free normalized fringe patterns and local pixel transforms for strain
      extraction.
AB  - Noise reduction is one of the most exciting problems in automatic fringe
      processing. We propose a two-dimensional (2-D) envelope transform for
      normalization of fringe patterns, coupled with spin filtering, to construct so
      called noise-free normalized fringe patterns. The 2-D envelope transform uses
      correct fringe intensity envelopes for normalization of fringe patterns, i.e.,
      for making the fringe background and amplitude constant over the whole field.
      Spin filtering is applied to fringe patterns for removal of random noise taking
      into account fringe flow. With spin filtering and the 2-D envelope transform, a
      noise-free normalized fringe pattern is constructed for postprocessing. Based on
      this improved fringe pattern, two local pixel transforms for strain extraction
      from a single moire pattern are developed, in which the digital pure secondary
      moire method is improved and the strain-field image method with division is
      developed.

PMID- 21102776
TI  - Phase-stepped television holographic technique for measuring phase and amplitude
      maps of small vibrations.
AB  - Phase stepping between frames in TV holography is combined with sinusoidal phase
      modulation to determine phase and amplitude distributions of objects vibrating
      with small amplitudes (<lambda/20, where lambdais the wavelength of the laser
      light used). This technique has applications in, for example, optical modal
      analysis and the determination of harmonic sound fields in air and water. The
      noise reduction that is obtained with the phase-stepping technique reduces the
      number of interferograms needed by one-half, which can shorten experimental time.
      The technique is robust, easy to use, and illustrated by modes of vibration in a
      simple plate and in a more complicated structure (a violin).

PMID- 21102777
TI  - Fringe detection in noisy complex interferograms.
AB  - A new algorithm to estimate the two-dimensional local frequencies of phase
      interferometric data is described. With a complex sine-wave model, demonstration
      is given that a conventional multiple-signal classification (MUSIC) algorithm can
      be used in spite of multiplicative noise perturbations. A faster algorithm
      dedicated to the processing of interferograms is developed and a measure of
      confidence in the estimate is proposed. We studied numerical performances using
      synthetic fringes. As a result of the frequency estimation, knowledge of the
      fringe local width and orientation can be applied to restore noisy phase data.
      Results of a complex phase filter are presented for real interferograms obtained
      from synthetic aperture radar images.

PMID- 21102778
TI  - Kinoform-only Gaussian-to-rectangle beam shaper for a semiconductor laser.
AB  - A kinoform that shapes the divergent beam from a semiconductor laser without
      using any other optical components was designed and fabricated. The kinoform-only
      concept means that the kinoform must perform both the actual beam shaping as well
      as focusing the divergent laser beam, correcting for the astigmatism of the
      laser, and correcting for the spherical aberration of the laser exit window. A
      rectangular beam of dimensions 1000 um * 300 um is formed 42 mm behind the
      kinoform. Of the total output from the laser, some 50% is incident upon the
      kinoform, of which ~50% will appear in the rectangular beam. The intensity
      uniformity error within the rectangle increases from the design value of 8% to
      38% because of sensitivity to fabrication errors. The kinoform-only design for
      beam-shaping applications requires high manufacturing accuracy but is attractive
      because a system using such a component is easily mounted and aligned and, with
      the use of kinoform-replication techniques, can be mass produced at low cost.

PMID- 21102779
TI  - Efficient optical packet-generation and -compression scheme.
AB  - An efficient optical packet-generation and -compression scheme is proposed.
      Packet compression is achieved when the packet is sent through a series of
      semiconductor optical amplifiers, which have either a transmitting or an
      absorbing state. The proposed scheme requires no fast electronics and uses
      exceptionally simple devices such as a tapped series of D flip-flops and
      frequency dividers. A detailed performance analysis on the system size
      limitations is also provided by the consideration of pulse-spreading effects and
      semiconductor optical-amplifier noise.

PMID- 21102780
TI  - Four-plane space-variant Fresnel-transform optical processor with a random phase
      encoder.
AB  - We introduce a four-plane Fresnel-transform space-variant optical processor
      consisting of an input plane and two filter planes. One filter mask is
      programmable with a spatial light modulator. The second filter mask is a fixed
      random binary phase array with a known pseudorandom distribution of pixels. The
      order of the masks can be interchanged, giving different output characteristics.
      In one case the Horner efficiency of the correlator increases dramatically. In
      the other case the edge enhancement of the output image is removed. We discuss
      the theory for this general processor and its implementation with phase-only
      masks. We present experimental results when a binary magneto-optic spatial light
      modulator was used.

PMID- 21102781
TI  - Effects of optical bias on moving gratings in bismuth silicon oxide at large
      fringe modulation.
AB  - Optical bias has been applied in the formation of moving gratings in bismuth
      silicon oxide at large fringe modulations. It is shown that optical bias is an
      effective method of overcoming the problems associated with the sudden drop in
      the optimum fringe velocity when the fringe modulation is close to unity. It is
      experimentally found that within a certain range of optical bias the absolute
      diffraction efficiency can be higher than that without optical bias, which is not
      the case when a stationary grating is used.

PMID- 21102782
TI  - Polarization holographic gratings in side-chain azobenzene polyesters with linear
      and circular photoanisotropy.
AB  - We investigate thin phase polarization holographic gratings recorded with two
      waves with orthogonal linear polarizations in materials in which illumination
      with linearly/circularly polarized light gives rise to linear/circular
      birefringence. The theoretical analysis shows that the presence of circular
      photoanisot-ropy changes significantly the diffraction characteristics of the
      gratings. The intensities of the waves diffracted in the +1 and -1 orders of
      diffraction and their ratio depend substantially on the reconstructing-wave
      polarization. Experiments with films of side-chain liquid-crystalline azobenzene
      polyester that is a photoanisotropic material of the considered type confirm the
      unusual polarization properties. It is shown that polarization holography may be
      used for real-time simultaneous measurement of photoinduced linear and circular
      birefringence.

PMID- 21102783
TI  - Noise analysis for the holographic first-arriving-light technique.
AB  - A noise analysis is performed on an electronic holography first-arriving-light
      system. Analytical expressions for the signal-to-noise ratio caused by the
      dominant noise terms are derived. The effect of various system parameters on the
      signal-to-noise ratio is explored; numerical and experimental examples are given.

PMID- 21102784
TI  - Analysis of optical near-field images by Karhunen-Loeve transformation.
AB  - With regard to classical image transformations, the Karhunen-Loeve transform is
      based on the statistical analysis of signal or image data. We propose using it to
      analyze and recognize the content of images generated in near-field microscopy.
      It is shown that such a transform is an efficient tool for separating actual
      information from noise without reducing the spatial-frequency band.

PMID- 21102785
TI  - Projection-invariant pattern recognition with a phase-only logarithmic-harmonic
      derived filter.
AB  - A phase-only filter based on logarithmic harmonics for projection-invariant
      pattern recognition is presented. This logarithmic-harmonic-derived filter is
      directly calculated in the Fourier plane. With respect to normal logarithmic
      harmonic filters it provides a smaller variation of the correlation intensity
      with the projection factor of the target. Computer and optical experiments are
      presented.

PMID- 21102786
TI  - Visual pattern recognition network: its training algorithm and its optoelectronic
      architecture.
AB  - A visual pattern recognition network and its training algorithm are proposed. The
      network constructed of a one-layer morphology network and a two-layer modified
      Hamming net. This visual network can implement invariant pattern recognition with
      respect to image translation and size projection. After supervised learning takes
      place, the visual network extracts image features and classifies patterns much
      the same as living beings do. Moreover we set up its optoelectronic architecture
      for real-time pattern recognition.

PMID- 21102787
TI  - Convolution-kernel-based optimal trade-off filters for optical pattern
      recognition.
AB  - An architecture for the implementation of optical pattern recognition is proposed
      that makes use of convolution-kernel-based optimal trade-off filters to allow for
      an increased speed of operation and filter storage capability. The derivation of
      these new convolution-kernel-based optimal trade-off filters is presented, and
      their noise robustness and discrimination capabilities are discussed.

PMID- 21102788
TI  - Two methods of reducing the dynamic range of a holographic filter.
AB  - Two methods of reducing the dynamic range of the transmittance of computer
      generated interconnection holograms are presented and compared. The holograms are
      used in an optical implementation of an associative memory to connect the input
      and the output planes but are representative of more generalN(4) interconnection
      holograms. Because the holograms play a double correlation-reconstruction role,
      the standard spectrum-smoothing techniques (e.g., random phase) cannot be
      applied. We show, in computer simulations and optical experiments, that by using
      deterministic phase functions that can be realized in the optical system
      (defocusing the hologram or controlling the phases of the diffraction spots of a
      Dammann grating used in the system input) the hologram dynamic range can be
      lowered, reducing the errors during the hologram binarization and increasing the
      hologram's diffraction efficiency.

PMID- 21102789
TI  - Double-multiplexed computer-generated holograms.
AB  - One of the detour-phase computer-generated-hologram encoding methods was improved
      for obtaining two objects simultaneously without increasing the plotter
      resolution. The encoded patterns were reconstructed along two orthogonal
      diffraction directions. Such a hologram could be useful for two-channel coherent
      or incoherent optical correlation. Laboratory experiments demonstrate the
      suggested technique.

PMID- 21102790
TI  - Diffraction efficiency of a grating coupler for an array illuminator.
AB  - The diffraction efficiency of a grating coupler having a surface-relief grating
      is calculated by the use of coupled-wave theory. The grating couplers are
      fabricated to examine the validity of the calculated result. The dependence of
      the measured diffraction efficiency on the groove depth of the grating coupler
      agrees well with the calculated results. The array illuminator, which emits 10
      and 20 beams with equal intensity, is designed and fabricated through the use of
      these numerical results. The uniformity error of the output beam caused by the
      error of the diffraction efficiency is also discussed.

PMID- 21102791
TI  - Achromatic waveguide coupling with a hybrid grating-mirror.
AB  - A new grating coupler that incorporates a hybrid grating-mirror is proposed. An
      analysis of the device indicates that it has a much larger achromatic range than
      that of conventional grating couplers, as well as a relaxed fabrication
      requirement for the grating.

PMID- 21102792
TI  - Truncation artifacts in tomographic reconstructions from projections.
AB  - The artifacts in tomographic reconstructions from truncated sets of projections
      are analyzed. The shift-variant impulse response of the tomographic system for
      parallel-beam geometry is derived. A number of propositions are made describing
      the observed artifacts. A graphical scheme for the prediction of the location and
      shape of the truncation artifacts is presented and applied to reconstructions
      from simulated projections. The artifact analysis is applied to images obtained
      with the commonly used convolution backprojection reconstruction algorithms, and
      it is extended to reconstructions from fan-beam projections. The analysis is
      performed for the continuous imaging domain so as to separate the clipping
      artifacts clearly from those attributed to the digital implementation of the
      reconstruction algorithms.

PMID- 21102793
TI  - Analysis of error-correction constraints in an optical disk.
AB  - The compact disk read-only memory (CD-ROM) is a mature storage medium with
      complex error control. It comprises four levels of Reed Solomon codes allied to a
      sequence of sophisticated interleaving strategies and 8:14 modulation coding. New
      storage media are being developed and introduced that place still further demands
      on signal processing for error correction. It is therefore appropriate to explore
      thoroughly the limit of existing strategies to assess future requirements. We
      describe a simulation of all stages of the CD-ROM coding, modulation, and
      decoding. The results of decoding the burst error of a prescribed number of
      modulation bits are discussed in detail. Measures of residual uncorrected error
      within a sector are displayed by C1, C2, P, and Q error counts and by the status
      of the final cyclic redundancy check (CRC). Where each data sector is encoded
      separately, it is shown that error-correction performance against burst errors
      depends critically on the position of the burst within a sector. The C1 error
      measures the burst length, whereas C2 errors reflect the burst position. The
      performance of Reed Solomon product codes is shown by the P and Q statistics. It
      is shown that synchronization loss is critical near the limits of error
      correction. An example is given of miscorrection that is identified by the CRC
      check.

PMID- 21102794
TI  - Optical illustration of a varied fractional Fourier-transform order and the Radon
      Wigner display.
AB  - Based on an all-optical system, a display of a fractional Fourier transform with
      many fractional orders is proposed. Because digital image-processing terminology
      is used, this display is known as the Radon-Wigner transform. It enables new
      aspects for signal analysis that are related to time- and spatial-frequency
      analyses. The given approach for producing this display starts with a one
      dimensional input signal although the output signal contains two dimensions. The
      optical setup for obtaining the fractional Fourier transform was adapted to
      include only fixed free-space propagation distances and variable lenses. With a
      set of two multifacet composite holograms, the Radon-Wigner display has been
      demonstrated experimentally.

PMID- 21102795
TI  - Fractional Wiener filter.
AB  - The fractional correlation is a new operation that can easily be implemented by
      optical means. This operation might be useful for shift-variant pattern
      recognition and for image restoration. The Wiener filter is the optimal filter
      according to the minimal square-error criterion. For a given spectral noise that
      distorts the reference image, this filter is optimal for restoring an image in
      noise. A fractional Wiener filter is suggested for restoring reference objects in
      a fractional correlation system. The new filter sometimes performs better than
      the conventional Wiener filter.

PMID- 21102796
TI  - Real-time signal classification with an acousto-optic triple-product processor
      cascaded into a volume holographic classifier.
AB  - An all-optical generalized linear machine applied to a high-bandwidth temporal
      signal-classification problem is demonstrated. The classifier consists of a
      dimensional increasing acousto-optic triple-product processor feature extractor
      cascaded through an optically addressed spatial light modulator into a volume
      holographic implementation of a linear classifier. Multiple-expo sure
      implementations of learning are used to train the classifier interconnection
      weights in a photorefractive crystal for a training set of wide-bandwidth
      temporal signals input to the acousto-optic triple-product processor.
      Experimental implementation of high-speed, time-shift and Doppler invariant, wide
      bandwidth signal identification is demonstrated.

PMID- 21102797
TI  - Space-variant simultaneous detection of several objects by the use of multiple
      anamorphic fractional-Fourier-transform filters.
AB  - A fractional correlator that is based on the anamorphic fractional Fourier
      transform is defined. This new, to our knowledge, correlator has been extended to
      work with multiple filters. The novelty introduced by the suggested system is the
      possibility of the simultaneous detection of several objects in different parts
      of the input scene (when anamorphic optics are dealt with), thereby permitting an
      independent degree of space invariance in two perpendicular directions. Computer
      experiments as well as experimental optical implementation are presented.

PMID- 21102798
TI  - Analysis of direct three-dimensional image transmission through optical fibers by
      the use of coherence methods.
AB  - The use of a grating interferometer under spatially incoherent illumination for
      direct three-dimensional image transmission through optical fibers is analyzed.
      The issues of resolution, image depth, and signal-to-noise ratio are addressed.
      Experimental results are presented.

PMID- 21102800
TI  - Feature issue on applied spectroscopy for sensors and chemical analysis:
      introduction.

PMID- 21102799
TI  - Recovery of optical cross-section perturbations in dense-scattering media by
      transport-theory-based imaging operators and steady-state simulated data.
AB  - We present a useful strategy for imaging perturbations of the macroscopic
      absorption cross section of dense-scattering media using steady-state light
      sources. A perturbation model based on transport theory is derived, and the
      inverse problem is simplified to a system of linear equations, WDeltaMU = DeltaR,
      where W is the weight matrix, DeltaMU is a vector of the unknown perturbations,
      and DeltaR is the vector of detector readings. Monte Carlo simulations compute
      the photon flux across the surfaces of phantoms containing simple or complex
      inhomogeneities. Calculation of the weight matrix is also based on the results of
      Monte Carlo simulations. Three reconstruction algorithms-conjugate gradient
      descent, projection onto convex sets, and the simultaneous algebraic
      reconstruction technique, with or without imposed positivity constraints-are used
      for image reconstruction. A rescaling technique that improves the conditioning of
      the weight matrix is also developed. Results show that the analysis of time
      independent data by a perturbation model is capable of resolving the internal
      structure of a dense-scattering medium. Imposition of positivity constraints
      improves image quality at the cost of a reduced convergence rate. Use of the
      rescaling technique increases the initial rate of convergence, resulting in
      accurate images in a smaller number of iterations.

PMID- 21102801
TI  - Tunable infrared laser detection of pyrolysis products of explosives in soils.
AB  - A research program involving two applications of tunable infrared laser
      differential absorption spectroscopy (TILDAS) with multipass, long-path
      absorption cells to the detection of explosives contamination in soils is
      reported. In the first application, sensitive, specific real-time species
      concentration measurements by TILDAS have led to new understanding of the
      processes involved in explosives detection by the heating of contaminated soils
      and the quantification of the resulting pyrolysis gases. In the second, we
      present results of our calculations of the properties of astigmatic off-axis
      resonator absorption cells, which show that useful TILDAS path lengths can be
      achieved inside a cone penetrometer probe.

PMID- 21102802
TI  - 2,4,6-Trinitrotoluene detection by laser-photofragmentation-laser-induced
      fluorescence.
AB  - Photofragmentation (PF) and subsequent nitric oxide (NO) laser-induced
      fluorescence (LIF) is being developed to measure the concentration of energetic
      materials (EM's) in soil and other media. Laser radiation near 226 nm
      photodissociates gas-phase EM to NO(2), which predissociates into NO that gives
      an intense luminescence. The EM concentration is inferred from the intensity of
      the NO fluorescence. We have studied the factors that affect the PF-LIF signal
      intensity, including the effect of buffer gas on the LIF spectrum of pure NO, the
      effect of 2,4,6-trinitrotoluene (TNT) pressure on the PF-LIF spectrum, the effect
      of buffer-gas pressure on the PF-LIF signal intensity of pure TNT, and the effect
      of temperature on the PF-LIF spectra of pure TNT and of TNT in simulated soil.
      Heating of the TNT sample above 343 K was found to increase the magnitude of the
      PF-LIF signal intensity significantly, but also was found to cause physical and
      chemical changes in the TNT sample. The effects of heating and evacuating on the
      TNT sample were investigated. TNT concentration calibration curves were obtained
      for TNT in simulated soil mixtures. The limit of detection of TNT in soil was
      estimated to be 40 parts in 10(9).

PMID- 21102803
TI  - Quantitative measurements by Fourier-transform infrared spectroscopy of toxic gas
      production during inhibition of JP-8 fires by CF(3)Br and C(3)F(7)H.
AB  - Fourier-transform infrared spectroscopy is used to monitor gases generated during
      chemical inhibition of JP-8 fuel pool fires burning in air. Gas samples are taken
      from a location that approximates the position of an individual who is using a
      handheld extinguisher to subdue the fire. These gas samples are flowed through a
      10-m path-length multipass optical cell placed in the sample beam of a Fourier
      transform infrared spectrometer. Gas samples are analyzed before and during
      application of C(3)F(7)H (trade name FM200) and CF(3)Br (Halon 1301) to the fire.
      It is shown that application of these halogenated hydrocarbons to JP-8 pool fires
      produces significant quantities of acid gases (HF and HBr) and of CF(2)O. A
      calculation of the concentrations (in parts in 10(6)) of these gases and other
      gaseous combustion products, based on observed absorbances, is presented. We
      believe this is the first quantitative simultaneous measurement of HF, HBr, HCl,
      and CF(2)O production during chemical inhibition of real fires.

PMID- 21102804
TI  - Crank-angle-resolved laser-induced fluorescence imaging of NO in a spark-ignition
      engine at 248 nm and correlations to flame front propagation and pressure
      release.
AB  - Inside the combustion chamber of a spark-ignition engine, NO fluorescence is
      excited with a narrow-band tunable KrF excimer laser. The fluorescence light is
      detected by an intensified CCD camera that yields images of the NO distributions.
      Rotational-vibrational transitions of NO are excited by the A(2)Sigma+ ? X(2)Pi
      (0, 2) band system around 248 nm. Single laser shot planar NO distributions are
      obtained with good signal-to-noise ratio at all crank angles and allow us to
      locate areas of NO formation during combustion. The pressure within the
      combustion chamber is measured simultaneously with the NO distributions, which
      allows the evaluation of correlations between indicated work and NO formation.
      The crank-angle-resolved sequences of two-dimensional NO distributions and
      averaged pressure traces are presented for different engine-operating conditions.
      In addition, laser-induced predissociation fluorescence of OH excited by the same
      laser source is measured in order to visualize the corresponding flame front
      propagation and to compare the time of formation of NO relative to that of OH.

PMID- 21102805
TI  - Application of tunable diode laser diagnostics for temperature and species
      concentration profiles of inhibited low-pressure flames.
AB  - We have employed tunable diode laser absorption spectroscopy (TDLAS) to
      characterize low-pressure premixed CH(4)/O(2)/Ar flames inhibited with Halon 1301
      (CF(3)Br) and the candidate Halon alternative compounds FE-13 (CF(3)H) and HFC
      125 (C(2)F(5)H). This work is part of a larger program designed to help identify
      replacement fire-suppression compounds for the currently used Halon 1301. We have
      used CO two-line thermometry to profile the temperature in low-pressure laminar
      flames and have determined concentration profiles for a large number of flame
      species, including reactive intermediates. To date, we have detected 12 flame
      species by using TDLAS in our laboratory and report on seven of them here: CH(4),
      H(2)O, CO, CF(2)O, CF(2)H(2), CF(3)H, and CF(4). To the best of our knowledge,
      this is the first time the last four species have been observed in flame by the
      use of TDLAS. Our data are important for validating the detailed kinetic
      mechanisms of chemical flame inhibition. Our results indicate that TDLAS is a
      versatile and powerful diagnostic technique for studying combustion processes.

PMID- 21102806
TI  - Tunable diode-laser absorption measurements of methane at elevated temperatures.
AB  - A diode-laser sensor system based on absorption spectroscopy techniques has been
      developed to monitor CH(4) nonintrusively in high-temperature environments.
      Fundamental spectroscopic parameters, including the line strengths of the
      transitions in the R(6) manifold of the 2nu(3) band near 1.646 MUm, havebeen
      determined from high-resolution absorption measurements in a heated static cell.
      In addition, acorrected expression for the CH(4) partition function has been
      validated experimentally over thetemperature range from 400 to 915 K. Potential
      applications of the diode-laser sensor system includeprocess control, combustion
      measurements, and atmospheric monitoring.

PMID- 21102807
TI  - Thermally assisted fluorescence of laser-excited OH A(2)Sigma(+) as a flame
      diagnostic tool.
AB  - A simple laser-induced-fluorescence measurement technique for turbulent flame
      temperature and OH concentration measurement is proposed and successfully tested.
      The main idea is that a narrow-band tunable excimer laser beam (lambda = 308 nm)
      is focused into a turbulent atmospheric-pressure nonpremixed flame. The OH
      molecule Q(1)(3) (X(2)II upsilon" = 0, A(2)Sigma+upsilon" = 0) transition is
      excited. By subsequent vibrational energy transfer, the distribution in the
      molecules' upper electronic energy level (excited Sigma(+) state) is
      redistributed. By evaluating the spectrum of the broadband emission from the
      upsilon' = 1 ? upsilon" = 0 and upsilon' = 2 ? upsilon" = 1 bands with a full
      spectral fit, we were able to evaluate the temperature and the OH molecule
      density. The concurrent processes of quenching, vibrational energy transfer, and
      rotational energy transfer were taken into account in the evaluation process. The
      results were compared with numerical flame calculations and revealed good
      agreement. One problem with this new proposed application of laser-induced
      fluorescence is the self-absorption of the emitted light. This, however, is shown
      not to be serious, but it has to be checked carefully. The main advantages are a
      simple experimental setup and procedure, high signal intensity, and a simple and
      straightforward data evaluation method. Thus this measurement technique is
      suitable for turbulent flame temperature and OH concentration measurement, and it
      is an alternative to other well-established techniques that are much more
      complicated.

PMID- 21102808
TI  - Methane detection with a narrow-band source at 3.4 um based on a Nd:YAG pump
      laser and a combination of stimulated Raman scattering and difference frequency
      mixing.
AB  - We report the characterization of a 10-Hz pulsed, narrow-band source that is
      coincident with a fundamental nu(3) rovibrational absorption of methane at 3.43
      um. To generate this midinfrared wavelength, an injection-seeded 1.06-um Nd:YAG
      laser is difference frequency mixed with first Stokes light generated in a high
      pressure methane cell (1.06 ? 1.54 um) to result in light at a wavelength of 3.43
      um, that is, the nu(1) Raman active frequency of methane (~2916.2 cm(-1)). With a
      modest-energy Nd:YAG laser (200 mJ), a few millijoules of this midinfrared energy
      can be generated with a pulse width of ~7 ns (FWHM). The methane nu(1) frequency
      can be pressure tuned over 8-32 atm (corresponding to ~13 GHz) and scanned across
      part of the nu(3)P(10) rovibrational level of methane, resulting in a peak
      measured methane absorption coefficient of 4.2 cm(-1) atm(-1).

PMID- 21102809
TI  - Detection of NO and NO(2) by (2 + 2) resonance-enhanced multiphoton ionization
      and photoacoustic spectroscopy near 454 nm.
AB  - Trace concentrations of NO and NO(2) are detected with a dye laser operating near
      454 nm. NO is detected by a (2 + 2) resonance-enhanced multiphoton ionization
      process by means of NO A(2)Sigma+-X(2)Pi(0, 0) transitions with miniature
      electrodes, and NO(2) is detected by a one-photon absorption photoacoustic
      process by means of NO(2)A-' (2)B(1)(0, 8, 0)- X- (2)A(1)(0, 0, 0) transitions
      with a miniature microphone. Rotationally resolved excitation spectra show that
      the spectral resolution is sufficiently high to identify these species at 1 atm.
      The technique's analytical merits are evaluated as functions of concentration,
      pressure, and laser intensities. Low laser intensities favor NO(2) photoacoustic
      detection whereas high laser intensities favor NO ionization. Limits of detection
      (signal-to-noise ratio 3) of 160 parts in 10(9) for NO and 400 parts in 10(9) for
      NO(2) are determined at 1 atm for a 10-s integration time. Signal response and
      noise analyses show that three decades of NO/NO(2) mixtures can be measured with
      a computational relative error in concentration that is three times the relative
      error in measuring the NO and NO(2) signals.

PMID- 21102810
TI  - Ultrasensitive, visible tunable diode laser detection of NO(2).
AB  - Recent advances in room-temperature visible diode lasers and ultrasensitive
      detection techniques have been exploited to create a highly sensitive tunable
      diode laser absorption technique for in situ monitoring of NO(2) in the lower
      troposphere. High sensitivity to NO(2) is achieved by probing the visible
      absorption band of NO(2) with an AlGalnP diode laser at 640 or 670 nm combined
      with a balanced ratiometric electronic detection technique. We have demonstrated
      a sensitivity of 3.5 * 10(10) cm(-3) for neat NO(2) in a 1-m path at 640 nm and
      have estimated a sensitivity for ambient operation of 5 ppbv m (l0 ppbv m at 670
      nm), where ppbvm is parts in 10(9) by volume per meter of absorption path length,
      from measured pressure-broadening coefficients.

PMID- 21102811
TI  - Tunable diode-laser absorption measurements of NO(2) near 670 and 395 nm.
AB  - Two single-mode diode lasers were used to record high-resolution absorption
      spectra of NO(2) (dilute in Ar) near 670.2 and 394.5 nm over a range of
      temperatures (296 to 774 K) and total pressures (2.4 * 10(-2) to 1 atm). A
      commercial InGaAsP laser was tuned 1.3 cm(-1) at a repetition rate of 1 kHz to
      record the absorption spectra near 670.2 nm. In separate experiments with a
      prototype system, an external-cavity GaAlAs laser was frequency doubled with a
      quasi-phase-matched LiNbO(3) waveguide and tuned 3.5 cm(-1) to record absorption
      spectra near 394.5 nm. Variations of the spectral absorption coefficients with
      temperature and pressure were determined from measured spectra.

PMID- 21102812
TI  - Photoacoustic spectroscopy on trace gases with continuously tunable CO(2) laser.
AB  - A novel photoacoustic (PA) system that uses a continuously tunable high-pressure
      CO(2) laser as radiation source is presented. A minimum detectable absorption
      coefficient of 10(-6) cm(-1) that is limited mainly by the desorption of
      absorbing species from the cell walls and by residual electromagnetic
      perturbation of the microphone electronics has currently been achieved. Although
      a linear dependence of the PA signal on the gas concentration has been observed
      over 4 orders of magnitude, the dependence on energy exhibits a nonlinear
      behavior owing to saturation effects in excellent agreement with a theoretical
      model. The calibration of the laser wavelength is performed by PA measurements on
      low-pressure CO(2) gas, resulting in an absolute accuracy of +/- 10(-2) cm(-1).
      PA spectra are presented for carbon dioxide (CO(2)), ammonia (NH(3)), ozone
      (O(3)), ethylene (C(2)H(4)), methanol (CH(3)OH), ethanol (C(2)H(5)OH), and
      toluene (C(7)H(8)) in large parts of the laser emission range. The expected
      improvement in detection selectivity compared with that of studies with line
      tunable CO(2) lasers is demonstrated with the aid of multicomponent trace-gas
      mixtures prepared with a gas-mixing unit. Good agreement is obtained between the
      known concentrations and the concentrations calculated on the basis of a fit with
      calibration spectra. Finally, the perspectives of the system concerning air
      analyses are discussed.

PMID- 21102813
TI  - Rational design of fiber-optic probes for visible and pulsed-ultraviolet
      resonance Raman spectroscopy.
AB  - We investigated the performance of fiber-optic resonance Raman probes with a
      series of experiments to determine the working curves of such probes using model
      analytes and to investigate the effects of absorbing media. A computer model
      designed to simulate these experiments is presented, and numerical results are
      found to be in agreement with the experimental data. Design considerations
      resulting from these studies are discussed, and novel designs for overcoming
      problems of coupling efficiency, damage threshold, and sensitivity in absorbing
      samples are presented. These findings are applied to the design of fiber-optic
      probes for ultraviolet resonance Raman spectroscopy involving nanosecond pulsed
      ultraviolet excitation (225 and 266 nm). These probes have been used to collect
      what is, to our knowledge, the first reported fiber-optic-linked ultraviolet
      resonance Raman spectra of tryptophan and DNA.

PMID- 21102814
TI  - Microspectrometer with slab-waveguide transmission gratings.
AB  - An integrated transmission diffraction grating in a planar optical waveguide is
      presented for broadband spectroscopic analysis of liquids and gases. Silicon
      oxynitride slab waveguides on silicon substrates with low optical loss in the
      visible range are combined with a phase transmission grating exhibiting a blaze
      effect at 500 nm to achieve high-efficiency diffraction and high spectral
      dispersion. Collimated white light propagates through the waveguide and couples
      into air at a stepped formed planar grating. The beams of each adjacent step
      interfere constructively at the focal line of a cylindrical lens, its focal line
      positioned perpendicular to the waveguide plane. We used a common silicon
      photodiode array to detect the spectral data. Our approach is to develop a
      compact and economic spectrometer without moving parts that can be applied for UV
      visible analysis and near-infrared industrial process control as well.

PMID- 21102815
TI  - Kramers-Kronig analysis of molecular evanescent-wave absorption spectra obtained
      by multimode step-index optical fibers.
AB  - Spectral distortions that arise in evanescent-wave absorption spectra obtained
      with multimode step-index optical fibers are analyzed both theoretically and
      experimentally. Theoretical analysis is performed by the application of Kramers
      Kronig relations to the real and the imaginary parts of the complex refractive
      index of an absorbing external medium. It is demonstrated that even when the
      extinction coefficient of the external medium is small, anomalous dispersion of
      that medium in the vicinity of an absorption band must be considered. Deviations
      from Beer's law, band distortions, and shifts in peak position are quantified
      theoretically as a function of the refractive index and the extinction
      coefficient of the external medium; the effect of bandwidth for both Lorentzian
      and Gaussian bands is also evaluated. Numerical simulations are performed for two
      types of sensing sections in commonly used plastic-clad silica optical fibers.
      These sensors include an unclad fiber in contact with a lower-index absorbing
      liquid and a fiber with the original cladding modified with an absorbing species.
      The numerical results compare favorably with those found experimentally with
      these types of sensing sections.

PMID- 21102816
TI  - Laser bandwidth effects in quantitative cavity ring-down spectroscopy.
AB  - We have investigated the effects of laser bandwidth on quantitative cavity ring
      down spectroscopy using the (r)R transitions of the b(nu = 0)?X(nu = 0) band of
      molecular oxygen. It is found that failure to account properly for the laser
      bandwidth leads to systematic errors in the number densities determined from
      measured ring-down signals. When the frequency-integrated expression for the ring
      down signal is fitted and measured laser line shapes are used, excellent
      agreement between measured and predicted number densities is found.

PMID- 21102817
TI  - Time-resolved fluorescence spectroscopy for chemical sensors.
AB  - A family of sensors is presented with fluorescence decay-time measurements used
      as the sensing technique. The concept is to take a single fluorophore with a
      suitably long fluorescence decay time as the basic building block for numerous
      different sensors. Analyte recognition can be performed by different functional
      groups that are necessary for selective interaction with the analyte. To achieve
      this, the principle of excited-state electron transfer is applied with pyrene as
      the fluorophore. Therefore the same instrumentation based on a small, ambient air
      nitrogen laser and solid-state electronics can be used to measure different
      analytes, for example, oxygen, pH, carbon dioxide, potassium, ammonium, lead,
      cadmium, zinc, and phosphate.

PMID- 21102818
TI  - Microwave characteristics of polymer electro-optic modulators.
AB  - The finite difference method is employed for the Laplace equation to calculate
      the microwave properties of polymer-based electro-optic modulators. The finite
      difference scheme uses a nonequidistant grid for fast calculation of the mode
      index and characteristic impedance of an open micro striplike modulator with a
      thick electrode as well as for a shielded micro striplike structure. It is
      demonstrated that the finite thickness of the electrode must be taken into
      consideration when optimizing the design of an electro-optic modulator. It is
      shown that by using a shielded microstrip configuration the modulator may be
      optimized and simultaneously pacified with regard to environmental influence.

PMID- 21102819
TI  - Monolithic formation of thin films on the vertical surface of a substrate by a
      dual-ion-beam sputtering technique.
AB  - We have developed a novel method for the selective deposition of thin films on
      the vertical surface of a planar substrate with a vertical step. This was done
      with a dual-ion-beam sputtering apparatus that is equipped with two ion-beam
      sources. Using this technique a multilayer filter was monolithically formed on
      the vertical surface of a Si substrate on which a photodetector had been
      fabricated, and clear filtering-photodetecting characteristics were observed.
      This technique can be applied to the monolithic integration of thin-film devices
      and waveguide-type optical devices with a vertical end facet.

PMID- 21102820
TI  - Internal reflection sensors with high angular resolution.
AB  - We discuss the use of total internal reflection for the production of sensors
      with high angular resolution. These sensors are intended for measurement of the
      angle between a sensor's axis and the direction to a source of radiation or
      reflecting object. Sensors of this type are used in controlling the position of
      machine parts in robotics and industry, orienting space vehicles and astronomic
      devices in relation to the Sun, and as autocollimators for checking angles of
      deviation. This kind of sensor was used in the Apollo space vehicle some 20 years
      ago. Using photodetectors with linear and area CCD arrays has opened up new
      application possibilities for appropriately designed sensors. A generalized
      methodology is presented applicable to a wide range of tasks. Some modifications
      that can improve the performance of the basic design are described.

PMID- 21102821
TI  - Wigner distribution function in nonlinear optics.
AB  - Transformation laws for the Wigner distribution function, the radiant intensity,
      the radiant emittance, and the first- and second-order moments of the Wigner
      distribution function through an inhomogeneous, Kerr-type medium have been
      derived as well as for the beam quality factor and the kurtosis parameter. It is
      shown that the inhomogeneous Kerr-type medium can be approximated from the Wigner
      distribution-function transformation-law point of view with a symplectic ABCD
      matrix with elements depending on the field distribution.

PMID- 21102822
TI  - Precise and versatile formula for birefringent filters.
AB  - In an investigation of extraordinary- (E-) ray behavior and the index of
      refraction for E waves in a uniaxial crystal, a precise and versatile formula for
      birefringent filters, based on the exact construction of the optical path
      difference, is set up with neither the approximation Deltan = n(o) - n(e) <= (or
      n(e)), nor the ambiguity sin(theta)sin(r(omega)) = n(e). The exact construction
      gives the correct variation of the position and the dimension in each path,
      yielding the path difference while the filter is tuning. The formula is
      applicable not only to a filter with its optical axis parallel to the entrance
      surface (PAPS) but also to a filter with its axis inclined to the surface (PAIS).
      Also, the formula indicates that a FAIS allows laser wavelengths to be tuned over
      a wider range than does a FAPS. The origin of the wider range is interpreted to
      be the greater variation in the index for the FAIS while the filter is tuning.
      With the help of the formula we design a FAIS for tuning a cw Ti:sapphire laser.

PMID- 21102823
TI  - Precisely tunable, narrow-band pulsed dye laser.
AB  - Anarrow-band, precisely tunable dye laser pumped by an injection-seeded YAG laser
      is described. The laser achieves an output of 100 mJ/pulse and 40% efficiency
      when one uses Rhodamine 6G dyes. The output pulse is Gaussian both in time and
      spatial profile. The laser oscillator employs an intracavity etalon that is
      repetitively pressure scanned over one free spectral range while the grating
      successively steps to consecutive etalon modes. We pressure scanned the etalon
      under computer control using a bellows. Methods are described for calibrating the
      tuning elements for absolute precision. We demonstrated that the laser has an
      absolute precision of +/-0.4 pm over a 1.0-nm scan. This accuracy is achievable
      over the wavelength range of a dye.

PMID- 21102824
TI  - Chromium-doped forsterite: the influence of crystal characteristics on laser
      performance.
AB  - A study of the dependence of the gain-switched laser operation of chromium
      forsterite on crystal parameters is presented. Results are reported for a wide
      range of chromium (IV) ion concentration: 0.02-0.12 at. % and 12-41 figure of
      merit, with emphasis on performance of the recently developed material with a
      dopant level of >0.10 at. %. Threshold and slope efficiency calculations are
      compared with measured performance for all crystals, with variation of pump
      polarization and output coupling. With 3% output coupling, the lowest threshold
      of 1.8 mJ, and highest slope efficiency of 13% were measured for a short, high
      dopant-level crystal. With 33% output coupling a slope efficiency of 44% was
      measured for this crystal. Results demonstrate the considerable potential of
      short, high-dopant-level crystals for applications such as amplification, diode
      pumping, and narrow-bandwidth operation.

PMID- 21102825
TI  - Improved frequency stability of an external cavity diode laser by eliminating
      temperature and pressure effects.
AB  - The construction of a passively stabilized external cavity diode laser operating
      at 780 nm is reported. The sensitivity of laser frequency to changes in air
      pressure was studied and subsequently eliminated. The relative frequency
      stability obtained was 4 * 10(-9) for an integration time of 4000 s.

PMID- 21102826
TI  - Atmospheric thermometry for metallic surfaces by laser-induced second-harmonic
      generation.
AB  - To the best of our knowledge we report the first demonstration of surface
      thermometry using laser-induced second-harmonic generation (SHG) on a realistic
      metallic surface at atmospheric pressure. The surface is probed with a pulsed
      infrared laser beam and the SHG signal is monitored in reflection. For metallic
      silver, the SHG signal is found to be temperature dependent in the 25-120
      omicronC range. The current accuracy of the method is ? omicronC. Future work
      with platinum should permit the application of SHG thermometry to much higher
      surface temperatures.

PMID- 21102827
TI  - Contrast and signal-to-noise ratio in long-distance starlight imaging.
AB  - A small telescope on an airplane or in low Earth orbit can, in principle, resolve
      ground objects under starlight with useful resolution. For an ~50-cm aperture and
      ~100-s exposure, one can obtain a resolution of tens of centimeters from an
      aircraft and a few meters from orbit. Such starlight images are photon poor, and
      feature detection depends on photon statistics. Scattered light, atmospheric
      absorption, and foreground airglow all degrade image contrast. I report an
      investigation into image signal-to-noise ratio using first-order analytical
      approximations. We find that, for a given angular resolution, the signal-to-noise
      ratio for spaceborne images is degraded approximately a factor of 1.7, compared
      with airborne images, by foreground airglow. Image signal-to-noise ratio improves
      as the passband moves to the red and as skies become brighter from artificial
      illumination.

PMID- 21102828
TI  - Optimum detection of multiple vapor materials with frequency-agile lidar.
AB  - Differential absorption lidar (DIAL) is a well-established technology for
      estimating the concentration and its path integral CL of vapor materials using
      two closely spaced wavelengths. The recent development of frequency-agile lasers
      (FAL's) with as many as 60 wavelengths that can be rapidly scanned motivates the
      need for detection and estimation algorithms that are optimal for lidar employing
      these new sources. I derive detection and multimaterial CL estimation algorithms
      for FAL applications using the likelihood ratio test methodology of multivariate
      statistical inference theory. Three model sets of assumptions are considered with
      regard to the spectral properties of the backscatter from either topographic or
      aerosol targets. The calculations are illustrated through both simulated and
      actual lidar data.

PMID- 21102829
TI  - Marine asymptotic daylight field: effects of inelastic processes.
AB  - The governing equations are developed for the marine asymptotic daylight field in
      the scalar approximation, including the effects of inelastic processes-Raman
      scattering and chromophoric dissolved organic matter fluorescence. The governing
      equations are solved numerically and compared with Monte Carlo simulations. It is
      found that these solutions are the actual radiance distributions approached by
      the asymptotic field in the Monte Carlo simulations. Sample solutions are
      provided to show the sensitivity of the light field to the various parameters of
      the medium. For certain values of the parameters, inclusion of inelastic
      processes can drastically alter the radiance distribution, e.g., from a near
      Dirac delta function in the absence of inelastic processes to a near-isotropic
      distribution in their presence. The results suggest that in a real ocean, the
      asymptotic (and near-asymptotic) radiance distribution will tend to become more
      uniform as the wavelength increases beyond ~500 nm. Finally, it is shown that
      even for depths far from the asymptotic regime, the radiance distribution of the
      inelastic component of the light field can be well approximated by the asymptotic
      theory developed here for inelastic processes. Two exact analytical solutions to
      the governing equations are also provided.

PMID- 21102830
TI  - Multipass optical absorption spectroscopy: a fast-scanning laser spectrometer for
      the in situ determination of atmospheric trace-gas components, in particular OH.
AB  - The optical design of an absorption spectrometer for in situ measurements of
      atmospheric trace gases is reported. The light source is a rapidly tuned and
      power-stabilized dye-ring laser, which is frequency doubled by an intracavity BBO
      crystal. The second harmonic and the fundamental are used simultaneously for
      measurement of OH, SO(2), CH(2)O, and naphthalene in the UV and of NO(2) in the
      visible. The 1.2-km absorption path is folded within a 6-m White-cell-type
      multiple-reflection system with an open-path setup. The absorption sensitivity of
      the spectrometer is better than 1 part in 10(-5) under tropospheric conditions
      (integration time 1 min., signal-to-noise ratio 1).

PMID- 21102831
TI  - Precision pointing and tracking through random media by exploitation of the
      enhanced backscatter phenomenon.
AB  - The active illumination of a target through a turbulent medium with a monostatic
      transmitter-receiver results in a naturally occurring conjugate wave caused by
      reciprocal scattering paths that experience identical phase variations. This
      reciprocal path-scattering phenomenon produces an enhanced backscatter in the
      retroverse direction (precisely along the boresight of the pointing telescope). A
      dual aperture causes this intensity enhancement to take the form of Young's
      interference fringes. Interference fringes produced by the reciprocal path
      scattering phenomenon are temporally stable even in the presence of time-varying
      turbulence. Choosing the width-to-separation ratio of the dual apertures
      appropriately and utilizing orthogonal polarizations to suppress the time-varying
      common-path scattered radiation allow one to achieve interferometric sensitivity
      in pointing accuracy through a random medium or turbulent atmosphere. Computer
      simulations are compared with laboratory experimental data. This new precision
      pointing and tracking technique has potential applications in ground-to-space
      laser communications, laser power beaming to satellites, and theater missile
      defense scenarios.

PMID- 21102832
TI  - Radiative transfer model: matrix operator method.
AB  - A radiative transfer model, the matrix operator method, is discussed here. The
      matrix operator method is applied to a plane-parallel atmosphere within three
      spectral ranges: the visible, the infrared, and the microwave. For a homogeneous
      layer with spherical scattering, the radiative transfer equation can be solved
      analytically. The vertically inhomogeneous atmosphere can be subdivided into a
      set of homogeneous layers. The solution of the radiative transfer equation for
      the vertically inhomogeneous atmosphere is obtained recurrently from the
      analytical solutions for the subdivided layers. As an example for the application
      of the matrix operator method, the effects of the cirrus and the stratocumulus
      clouds on the net radiation at the surface and at the top of the atmosphere are
      investigated. The relationship between the polarization in the microwave range
      and the rain rates is also studied. Copies of the FORTRAN program and the
      documentation of the FORTRAN program on a diskette are available.

PMID- 21102833
TI  - Processing wave-front-sensor slope measurements using artificial neural networks.
AB  - For adaptive-optics systems to compensate for atmospheric turbulence effects, the
      wave-front perturbation must be measured with a wave front sensor (WPS), and key
      parameters of the atmosphere and the adaptive-optics system must be known. Two
      parameters of particular interest include the Fried coherence length r(0) and the
      WPS slope measurement error. Statistics-based optimal techniques, such as the
      minimum variance phase reconstructor, have been developed to improve the imaging
      performance of adaptive-optics systems. However, these statistics-based models
      rely on knowledge of the current state of the key parameters. Neural networks
      provide nonlinear solutions to adaptive-optics problems while offering the
      possibility of adapting to changing seeing conditions. We address the use of
      neural networks for three tasks: (l) to reduce the WPS slope measurement error,
      (2) to estimate the Fried coherence length r(0), and (3) to estimate the variance
      of the WPS slope measurement error. All of these tasks are accomplished by using
      only the noisy WPS measurements as input. Where appropriate, we compare our
      method with classical statistics-based methods to determine if neural networks
      offer true benefits in performance. Although a statistics-based method is found
      to perform better than a neural network in reducing WPS slope measurement error,
      neural networks perform better in estimating the variance of the WPS slope
      measurement error, and both methods perform well in estimating r(0).

PMID- 21102834
TI  - Line Raman, Rayleigh, and laser-induced predissociation fluorescence technique
      for combustion with a tunable KrF excimer laser.
AB  - We have applied a line UV Raman, Rayleigh, and laser-induced predissociation
      fluorescence technique for measurement of turbulent hydrocarbon flames. The
      species concentration of CO(2), O(2), CO, N(2), CH(4), H(2)O, OH, and H(2) and
      the temperature are measured instantaneously and simultaneously along a line of
      11.4 mm, from which the gradients with respect to mixture fraction and spatial
      direction are obtained. The technique has been successfully tested in a laminar
      premixed stoichiometric methane flame and a laminar hydrogen diffusion flame. In
      addition the technique has been tested in a highly turbulent rich premixed
      methane flame. The data show that the technique can be used to provide
      instantaneous measurements of local profiles that describe the local flame
      structure in highly turbulent flames.

PMID- 21102835
TI  - Spectroturbidimetry of fractal clusters: test of density correlation function
      cutoff.
AB  - I have measured the relative increase in turbidity tau/tau(t = 0) as a function
      of wavelength exponent w = -?(log tau)/?(log lambda) in the process of the
      reaction-limited cluster-cluster aggregation of polystyrene latex with a particle
      diameter of 90 nm. It is shown that this dependence is not sensitive to
      particular details of sample preparation and is described for independent
      measurements by one master curve. Theoretical calculations made in the single
      scattering and Berry-Percival mean-field theory approximations considering small
      angle light-scattering effects and cluster polydispersity also demonstrate that
      this dependence is sufficiently universal and its shape can be practically
      determined solely by the choice of the density correlation function cutoff model.
      Comparing the experimental tau/tau(0) = f(w) curves with calculated theoretical
      plots I conclude that the Gaussian cutoff model is the best among all the models
      of the exponential family. This is in accord with a previous finding [Langmuir 8,
      2964-2069 (1992)] that was obtained by using angular scattering from diffusion
      limited cluster-cluster aggregation soot aggregates.

PMID- 21102836
TI  - Approximations to extinction from randomly oriented circular and elliptical
      cylinders.
AB  - Analytic approximations to the extinction efficiency, Qext, are given for
      oriented and randomly oriented circular infinite cylinders based on anomalous
      diffraction. The results are compared with the exact code. These results are
      further generalized to randomly oriented elliptical cylinders. With the use of
      the formulas, Qext can be evaluated over 10(4) times faster than with the exact
      code. This approximation is valid for complex refractive indices m = n - ik,
      where 1 <= n <= infinity and 0<= k <= 3, aspect ratios from 1 to 4, and modest to
      large particle sizes. The accuracy and limitations of these formulas are
      discussed.

PMID- 21102837
TI  - Far-field scattering of an axisymmetric laser beam of arbitrary profile by an on
      axis spherical particle.
AB  - Experimental laser beam profiles often deviate somewhat from the ideal Gaussian
      shape of the TEM(00) laser mode. In order to take these deviations into account
      when calculating light scattering, we propose a method for approximating the beam
      shape coefficients in the partial wave expansion of an experimental laser beam.
      We then compute scattering by a single dielectric spherical particle placed on
      the beam's axis using this method and compare our results to laboratory data. Our
      model calculations fit the laboratory data well.

PMID- 21102838
TI  - Applicability of regular particle shapes in light scattering calculations for
      atmospheric ice particles.
AB  - We ascertain the usefulness of simple ice particle geometries for modeling the
      intensity distribution of light scattering by atmospheric ice particles. To this
      end, similarities and differences in light scattering by axis-equivalent, regular
      and distorted hexagonal cylindric, ellipsoidal, and circular cylindric ice
      particles are reported. All the results pertain to particles with sizes much
      larger than a wavelength and are based on a geometrical optics approximation. At
      a nonabsorbing wavelength of 0.55 um, ellipsoids (circular cylinders) have a much
      (slightly) larger asymmetry parameter g than regular hexagonal cylinders.
      However, our computations show that only random distortion of the crystal shape
      leads to a closer agreement with g values as small as 0.7 as derived from some
      remote-sensing data analysis. This may suggest that scattering by regular
      particle shapes is not necessarily representative of real atmospheric ice
      crystals at nonabsorbing wavelengths. On the other hand, if real ice particles
      happen to be hexagonal, they may be approximated by circular cylinders at
      absorbing wavelengths.

PMID- 21102839
TI  - Determination of aerosol parameters from light-scattering data using an inverse
      Monte Carlo technique.
AB  - An inverse, Monte Carlo (IMC) technique is developed to solve the electromagnetic
      inverse-scattering problem from generally complex distributions of dielectric
      particles. One can verify the technique using simulated scattering data from
      aerosols composed of spherical dielectrics. The IMC method is found to give
      accurate inversion results even when the data have a signal-to-noise ratio to as
      low as 3:1.

PMID- 21102840
TI  - Patents.

PMID- 21102842
TI  - Fractality of speckle intensity fluctuations.
AB  - Coherent-light diffraction on random phase screens with fractal properties leads
      to the formation of speckle patterns with peculiarities in correlation
      characteristics in the small-scale region. Such peculiarities are manifested in
      asymptotic behavior in intensity autocorrelation and structure functions in the
      vicinity of the zero values of their arguments. Intensity fluctuations in the far
      and the near diffraction zones are also characterized by values of fractal
      (Hausdorff-Besicovitch) dimensions D(HB), differing from the corresponding
      Euclidean dimension. Relationships between the exponential factors of the
      structure functions of boundary field phase and scattered-light intensity
      fluctuations as well as between values of D(HB) have been obtained as a result of
      speckle-formation analysis for different conditions. Their dependencies on the
      illumination and observation conditions obtained in experiments with fractallike
      scatterers (rough glass plates) are in satisfactory agreement with theoretical
      results.

PMID- 21102841
TI  - Charge-coupled-device detection of soft x rays for grazing-incidence
      spectrometers.
AB  - We describe calculations of the sensitivity of CCD's to soft x rays incident at
      grazing angles. Soft-x-ray spectrometers based on a Rowland-circle geometry have
      a focal plane and hence detector surface at grazing incidence to the soft * rays.
      We model the penetration of the grazing-incidence soft * rays to the sensitive
      region of the CCD and predict the charge-collection efficiency as a function of
      wavelength. The results show significant advantages over microchannel plate
      intensified detection.

PMID- 21102843
TI  - Effective implementation of subtraction holography for noise suppression in
      particle fields.
AB  - A phase-stepped holographic system based on an electro-optic modulator has been
      developed. Subtraction holography is easily realized with our developed
      holographic system, so optical noise in particle fields is rejected entirely.
      This greatly improves the signal-to-noise ratio of the particle image and the
      resolution of the system. Experimental results illustrate such advantages.

PMID- 21102844
TI  - Wave-front-dividing circular-reflector interferometer for the far infrared.
AB  - The efficiency of a wave-front-dividing interferometer with circular symmetric
      sets of reflectors is studied and compared with that of a lamellar grating. The
      circular-reflector interferometer shows more efficient modulation over larger
      spectral regions in the far IR than the lamellar grating does. In contrast to
      Michelson and Martin-Puplett interferometers no beam splitters are employed.

PMID- 21102845
TI  - Wave-front recovery from two orthogonal sheared interferograms.
AB  - We present a new technique for using the information of two orthogonal lateral
      shear interferograms to estimate an aspheric wave front. The wave-front
      estimation from sheared inteferometric data may be considered an ill-posed
      problem in the sense of Hadamard. We apply Thikonov regularization theory to
      estimate the wave front that has produced the lateral sheared interferograms as
      the minimizer of a positive definite-quadratic cost functional. The introduction
      of the regularization term permits one to find a well-defined and stable solution
      to the inverse shearing problem over the wave-front aperture as well as to reduce
      wave-front noise as desired.

PMID- 21102846
TI  - Single-beam diode-laser technique for optical path-length measurements.
AB  - A simple single-beam technique employing radio-frequency modulation of a tunable
      diode laser with homodyne demodulation is demonstrated as a means of measuring
      optical path lengths. This technique offers a straightforward method for
      determining path lengths traversed through optical multipass cells or performing
      optical range-finding over short (i.e., tens of meters) standoff distances. The
      radio-frequency phase-sensitive nature of the technique permits narrow-band
      detection and high signal-to-noise ratios, even when range-finding measurements
      are made with range resolutions of "1 m. This compares favorably with traditional
      short-pulse, wide-bandwidth optical range finders.

PMID- 21102847
TI  - Effect of beat frequency on the measured phase of laser-diode heterodyne
      interferometry.
AB  - An optical heterodyne interferometer with a frequency-ramped laser diode has been
      constructed. The effect of the beat frequency on the measured phase has been
      theoretically investigated in the frequency domain and experimentally verified.
      Phase errors caused by the difference between the ramp frequency and the beat
      frequency alter sinusoidally in accordance with the pi periodicity of the
      interferogram. The error can be eliminated by the electronic calibration
      technique of the beat frequency.

PMID- 21102848
TI  - Tailored edge-ray designs for illumination with tubular sources.
AB  - The rubric tailored edge-ray designs (TED's) refers to the procedure for
      tailoring lighting reflectors to produce a prescribed flux distribution for an
      extended Lambertian source while ensuring maximum radiative efficiency (no
      radiation being returned to the source). Most TED studies to date have been
      restricted to the case in which the two edges of the image of the source in the
      reflectors are bound by a source edge ray and a reflector edge. The extension to
      the more general, and challenging, solution in which both edges of the image can
      be bound by rays from opposite edges of the source was recently begun by Ries and
      Winston [J. Opt. Soc. Am. A 11, 1260-1264 (1994)] but was described in detail
      only for one particular design. We show that there are four topologically
      distinct classes of such reflectors; we derive the governing differential
      equations and obtain the solution in analytical form. Our results are illustrated
      for the case of uniform far-field illuminance production with symmetric
      configurations in two dimensions. Relative to earlier TED's, these new devices
      can offer increased uniform core regions and superior glare control, although
      they are somewhat less compact. We offer a comprehensive analysis of the
      geometric properties, flux-map characteristics, and limitations of these new
      TED's.

PMID- 21102849
TI  - Polarization properties of cube-corner retroreflectors and their effects on
      signal strength and nonlinearity in heterodyne interferometers.
AB  - The polarization properties of solid-state cube-corner retroreflectors, which are
      uncoated glass or metal-coated glass on the reflecting surfaces, are examined
      analytically and compared. Experimental verifications are presented for the case
      of linearly polarized incident light. When the uncoated cube-corner is used in a
      heterodyne interferometer, the polarization properties reveal that the axial
      orientation of the corner reflector has an effect on the strength of the beat
      signal and the nonlinearity error. A theoretical analysis of the effect is
      presented together with experimental results.

PMID- 21102850
TI  - Achromatic wave retarder by phase subtraction.
AB  - We analyze the method of phase subtraction in two identical optical structures to
      build an achromatic phase retarder. The two structures are made of right-angle
      prisms and are aligned orthogonal to each other. They are also made of materials
      of different refractive indices so that dispersion compensation can be taken
      advantage of. Essentially the phase retardation between the s and p waves in the
      first structure is subtracted from the phase retardation in the second structure.
      This can be done by reversing the roles of the s and p waves. By choosing the
      materials of the prisms properly, the phase retardation can be made to be
      constant over a broad spectral range. Indeed, calculations made with commercial
      optical glasses show that phase errors in the visible and near-infrared regions
      can be rather small. For example, for a 90 degrees  phase retarder (quarter-wave
      plate), a phase error of 0.35 degrees  can be obtained from 0.35 to 0.81 MUm and
      from 0.59 to 1.26 MUm.

PMID- 21102851
TI  - Luminous-flux measurements by an absolute integrating sphere.
AB  - We present an original implementation of the absolute-sphere method recently
      proposed by Ohno. The luminous-flux unit, the lumen, is realized by means of an
      integrating sphere with an opening calibrated by a luminous-intensity standard
      placed outside. The adapted experimental setup permits one to measure luminous
      flux values between 5 and 2500 lm with a significant improvement with respect to
      the simulated performances reported in the literature. Traditionally, the
      luminous-flux unit, the lumen, is realized by goniophotometric techniques in
      which the luminous-intensity distribution is measured and integrated over the
      whole solid angle. Thus sphere results are compared with those obtained with the
      Istituto Elettrotecnico Nazionale goniophotometer. In particular, a set of
      standards, characterized by luminous-flux values of ~2000 lm, has been calibrated
      with both techniques. We highlight some of the problems encountered. Experimental
      results show that the agreement between the two methods is within the estimated
      uncertainty and suggest promising areas for future research.

PMID- 21102852
TI  - Realization of a scale of absolute spectral response using the National Institute
      of Standards and Technology high-accuracy cryogenic radiometer.
AB  - Using the National Institute of Standards and Technology high-accuracy cryogenic
      radiometer (HACR), we have realized a scale of absolute spectral response between
      406 and 920 nm. The HACR, an electrical-substitution radiometer operating at
      cryogenic temperatures, achieves a combined relative standard uncertainty of
      0.021%. Silicon photodiode light-trapping detectors were calibrated against the
      HACR with a typical relative standard uncertainty of 0.03% at nine laser
      wavelengths between 406 and 920 nm. Modeling of the quantum efficiency of these
      detectors yields their responsivity throughout this range with comparable
      accuracy.

PMID- 21102853
TI  - Stability under vacuum of silicon trap detectors and their use as transfer
      instruments in cryogenic radiometry.
AB  - The stability of the responsivity of trap detectors under vacuum has been studied
      by means of a special chamber designed for the test of photodetectors at low
      pressure. The first experiments at a wavelength of 647 nm show that the
      responsivity variations are smaller than the uncertainties of the measurements,
      approximately 3 parts in 10(5), when the detector operates successively in air,
      under vacuum, and then again in air. Calculations based on experiments with
      single windowless photodiodes indicate that the change in trap responsivity that
      is due to vacuum effects should be smaller than 1 part in 10(5), at least in the
      visible part of the wavelength range. This stability makes trap detectors
      suitable for cryogenic radiometry when one uses transfer detectors under vacuum.

PMID- 21102854
TI  - Reflectance of a wideband multilayer x-ray mirror at normal and grazing
      incidences.
AB  - The reflectance of a W-B(4)C multilayer mirror, with a period thickness that
      increased with depth into the multilayer, was measured at near-normal incidence
      with synchrotron radiation and at grazing incidence with Cu Kalpha radiation. The
      period thickness increased linearly from 17.9 A at the top of the multilayer
      structure to 21.9 A at the substrate while the same ratio of nodal layer to
      period thickness was maintained. For a grazing angle of 80 degrees  (10 degrees 
      from normal incidence), the peak reflectance was 1.1% at a wavelength of 36 A,
      and the reflectance profile was 1 A wide. For Cu Kalpha radiation the reflectance
      peaked at a grazing angle of 2.4 degrees  and was 0.4 degrees  wide. Compared
      with a W-B(4)C multilayer mirror with a constant period thickness, the depth
      graded multilayer mirror has wider reflectance profiles at near-normal and
      grazing incidences, resulting in larger integrated reflectances and wider fields
      of view.

PMID- 21102855
TI  - Fourier-transform design and electron cyclotron resonance plasma-enhanced
      deposition of lossy graded-index optical coatings.
AB  - A Fourier-transform synthesis technique is applied to the design of inhomogeneous
      refractive-index optical thin films with dispersion of refractive index and
      absorption taken into account. Using measured properties of SiO(x) N(y), we have
      designed a broadband reflector and two three-line filters with high reflectance.
      One of the three-line filters was manufactured by electron cyclotron resonance
      plasma-enhanced chemical vapor deposition from a mixture of SiH(4), N(2), O(2),
      and Ar. Good agreement between design and measured performance proves the
      feasibility of applying the Fourier-transform technique to the design of
      reflection filters even in the case of highly dispersive, absorbing material, if
      its optical properties are well characterized.

PMID- 21102856
TI  - X-ray focusing with lobster-eye optics: a comparison of theory with experiment.
AB  - We report an experimental investigation and comparison with simulation of the x
      ray focusing of a flat, square profile microchannel plate. We use x rays with an
      energy of ~1.5 keV from a laser-produced plasma. The images were recorded with x
      ray film. We find the focal structure to be consistent with theoretical
      expectations. The angular resolution of the focus is 0.96 mrad, which is a major
      improvement over previous results. The measured peak intensity gain is 27 +/- 4,
      which is ~33% of that for a perfect optic.

PMID- 21102857
TI  - Comparison of beam propagation method and rigorous coupled-wave analysis for
      single and multiplexed volume gratings.
AB  - Multiplexed holographic structures have been suggested to provide large capacity
      and parallel access as three-dimensional storage media. One of the most widely
      used techniques in the literature for analyzing such structures has been the
      coupled-wave analysis and its variations. Another approach that is becoming
      increasingly popular because of the ease with which it can be implemented is the
      beam propagation method (BPM). The BPM is quantitatively compared with the
      rigorous coupled-wave analysis for the cases of single and multiplexed gratings.
      Normal and off-normal incidence as well as TE and TM polarizations are considered
      for single (slanted and unslanted) and multiplexed gratings. It is shown that the
      BPM, even in its most rudimentary form, is a powerful and accurate calculational
      method that is especially suited for analyzing the many multiplexed grating
      diffraction problem.

PMID- 21102858
TI  - Experimental measurement of a time-varying optical path difference by the small
      aperture beam technique.
AB  - We discuss the use of time series of the jitter angle of multiple, small-aperture
      probe beams (the small-aperture beam technique, or SABT) as they emerge from a
      turbulent, optically active flow-field to quantify the time-varying optical path
      difference (OPD). The flow field studied is that for the transitionally turbulent
      region of a two-dimensional heated jet. Techniques to construct a complete time
      series of instantaneous realizations of the OPD are first applied to a
      numerically generated flow field and then to an experimental flow field. The SABT
      sensor's measurement accuracy is assessed, and its application to flow fields
      that differ from the numerical heated jet is discussed.

PMID- 21102859
TI  - Surface microroughness of optical glasses under deterministic microgrinding.
AB  - Deterministic microgrinding of precision optical components with rigid, computer
      controlled machining centers and high-speed tool spindles is now possible on a
      commercial scale. Platforms such as the Opticam systems at the Center for Optics
      Manufacturing produce convex and concave spherical surfaces with radii from 5 mm
      to infinity, i.e., planar, and work diameters from 10 to 150 mm. Aspherical
      surfaces are also being manufactured. The resulting specular surfaces have a
      typical rms microroughness of 20 nm, 1 MUm of subsurface damage, and a figure
      error of less than 1 wave peak to valley. Surface roughness under deterministic
      microgrinding conditions (fixed infeed rate) with bound abrasive diamond ring
      tools with various degrees of bond hardness is correlated to a material length
      scale, identified as a ductility index, involving the hardness and fracture
      toughness of glasses. This result is in contrast to loose abrasive grinding
      (fixed nominal pressure), in which surface microroughness is determined by the
      elastic stiffness and the hardness of the glass. We summarize measurements of
      fracture toughness and microhardness by microindentation for crown and flint
      optical glasses, and fused silica. The microindentation fracture toughness in
      nondensifying optical glasses is in good agreement with bulk fracture toughness
      measurement methods.

PMID- 21102860
TI  - Computationally directed axisymmetric aspheric figuring (after N. J. Brown).
AB  - We examine some computational problems related to the finishing of axisymmetric
      optical surfaces discussed in a paper by N. J. Brown [Opt. Eng. 17, 602-620
      (1978)]. In the spirit of Brown's paper we develop solution algorithms that are
      suitable for implementation on today's personal computers. The use of the
      algorithms is illustrated by some sample calculations.

PMID- 21102861
TI  - Microlenses fabricated by ultraviolet excimer laser irradiation of poly(methyl
      methacrylate) followed by styrene diffusion.
AB  - A new technique of microlens array fabrication based on the use of excimer laser
      radiation is described. Poly(methyl methacrylate) (PMMA) substrates are treated
      with many low-energy KrF laser pulses and exposed to styrene vapor. The
      irradiated material swells, producing spherical microlenses that are stabilized
      by UV polymerization. The chemistry of this process and the optical quality of
      the lenses are discussed.

PMID- 21102863
TI  - Time-resolved fluorescence-decay measurement and analysis on single cells by flow
      cytometry.
AB  - A novel method is described for the measurement and analysis of fluorescence
      decays of individual cells and particles in flow. It combines the rapid
      measurement capabilities of a flow cytometer and the robust measurement and
      analysis procedures of time-domain fluorescence-lifetime spectroscopy. For
      excitation we use a cw laser that is pulse modulated by an electro-optic
      modulator. The characteristics and the repetition rate of the excitation pulses
      can be easily adjusted to accommodate fluorescence decays with a wide range of
      lifetimes.

PMID- 21102862
TI  - Automated 360 degrees  profilometry of a three-dimensional diffuse object and its
      reconstruction by use of the shading model.
AB  - The 360 degrees  profilometry of a three-dimensional (3-D) diffuse object by use
      of the light intersection and its image reconstruction by surface shading are
      presented. The lack of data in one direction, which was due to occlusion, was
      compensated by the projection of two lines of light from different directions.
      Some experiments to profile objects and their reconstruction by computer are
      shown. The entire surface model was constructed, and a real shading image was
      obtained by means of computer graphics.

PMID- 21102864
TI  - Multilayer technology for diffractive optical elements.
AB  - The proposed multilayer technology makes it possible to approximate a continuous
      phase distribution by discrete phase steps. Compared with binary techniques, a
      higher diffraction efficiency can be achieved. In most known processes a bulk
      substrate is used and etched directly; therefore it is difficult to control the
      height of the phase steps. We propose applying layers of a well-known thickness
      and structuring them with a selective etching process. In this new multilayer
      process for reflecting elements a system of metal and dielectric layers is used
      that can easily be produced by standard methods.

PMID- 21102865
TI  - White-light imaging by use of a multiple passband acousto-optic tunable filter.
AB  - White-light imaging was accomplished by operation of a TeO(2) acousto-optic
      tunable filter (AOTF) with 40 simultaneous overlapping passbands from 400 to 700
      nm. The AOTF was chromatically compensated by a wedge applied to the output
      surface of the AOTF, and the measured spatial resolution correlated well with
      predictions. Switching off specific rf's applied to the AOTF produced optical
      rejection corresponding to the inactive passbands. A rejection ratio of 30 dB was
      demonstrated, and the rejection level was found to be controlled by leakage
      through the sidelobes of adjacent passbands.

PMID- 21102866
TI  - Vibration measurement by the time-averaged electronic speckle pattern
      interferometry methods.
AB  - Three different image-processing methods based on the time-averaged technique
      were compared by the electronic speckle pattern interferometry (ESPI) technique
      for vibration measurement. The three methods are the video-signal-addition
      method, the video-signal-subtraction method, and the amplitude-fluctuation
      method. Also, errors introduced by using the zero-order Bessel function directly
      into the analysis of the fringe pattern were investigated. The video-signal
      addition method has been the most generally used ESPI technique for vibration
      measurement. However, without additional image and/or signal-processing
      procedures, the fringe pattern obtained directly by the video-signal-addition
      method is rather difficult to observe. The reason for poor visibility of the
      experimentally obtained fringe pattern with this method is explained. To increase
      the fringe pattern's visibility without additional image and/or signal processes,
      we tried two video-signal-subtraction methods. One of the two methods is the
      video-signal-subtraction method that has normally been used in the static
      applications. The other method, called the amplitude-fluctuation method, and its
      associated theory are reported here.

PMID- 21102867
TI  - Interferometric model for phase analysis in fiber couplers.
AB  - An interferometric model is proposed to estimate the phase differences in
      lossless, strongly coupled biconical fiber couplers. This approximate method is
      simpler than the traditional s-parameter network theory-based analysis technique
      and minimizes the number of unknowns. The phase difference between the
      transmitted and coupled light fields is directly related to the field interaction
      and can be estimated by employing the energy conservation and mode orthogonality
      principles. The maximum coupling coefficient and dependence of phase difference
      on coupling conditions can be analyzed for multiport single-mode fiber couplers.

PMID- 21102868
TI  - Electric-arc cleaning of optical-fiber endfaces.
AB  - The cleaning action of the cleaning arc of two optical-fiber fusion-splicing
      devices is investigated. Interferometric analysis of the optical-fiber endfaces
      before and after exposure to the cleaning arcs reveals damage to the endfaces
      caused by one of the devices. The position of the fiber relative to the cleaning
      arc is thought to cause this damage.

PMID- 21102869
TI  - Zebra schlieren optics for leak detection.
AB  - A modification of schlieren optics was explored as a technique for industrial gas
      leak detection. A high-contrast pattern on thin reflecting material was imaged
      with a zoom lens onto a negative of the same pattern as a method of eliminating
      the ordinary rays. The geometry of the industrial setting determines the useful
      spatial frequency of the pattern.

PMID- 21102870
TI  - Interferometric distributed optical-fiber sensor.
AB  - An interferometric technique is described for detecting and locating
      perturbations along an optical fiber. This distributed sensor, based on a
      modified fiber-ring interferometer, has a position-dependent response to time
      varying disturbances such as strain or temperature. These disturbances cause a
      phase shift that is detected and converted to spatial information. The sensor
      consists of two parts, namely, a reflecting-fiber-ring interferometer and a
      differentiating-ring interferometer. The reflecting ring consists of a fiber ring
      with one port of the coupler connected to a reflector. Consequently the output
      port of the reflecting-ring interferometer is the same as the input port. Because
      it is an inherent zero-path-imbalanced system, a short-coherence-length source
      such as a light-emitting diode can be used. Any time-varying perturbation on the
      fiber in the ring results in a detector signal proportional to the product of the
      rate-of-phase change caused by the perturbation and the distance of the
      perturbation relative to the center of the fiber ring. The second part of the
      system, a differentiating-ring interferometer, consists of the same fiber-ring
      interferometer modified only slightly. The output of this part of the sensor is
      proportional only to the rate of phase change as a result of the unknown
      perturbation and contains no distance information. By dividing the output of the
      reflecting-ring interferometer by the output of the differentiating-ring
      interferometer, we determine disturbance location. Results obtained with a 155-m
      distributed fiber sensor are discussed.

PMID- 21102871
TI  - Effects of cryogenic grinding on soft-tissue optical properties.
AB  - Optical properties obtained from spectrophotometer measurements of reflectance
      and transmittance were determined for both frozen-ground and intact soft tissues.
      The tissues used in these experiments were calf aorta, rat jejunum, and rabbit
      sciatic nerve. Tissue specimens from each tissue type were frozen in liquid
      nitrogen and then ground with a pestle and mortar into a fine powder. A tissue
      paste formed once the powder returned to room temperature. The tissue paste was
      then sandwiched between glass slides for spectrophotometer measurements. For
      comparison, the optical properties of the intact specimens were also measured.
      Total transmission and diffuse reflection were obtained on a Varian Cary 5E
      spectrophotometer (400-850 nm). Absorption and reduced scattering coefficients of
      the tissues were determined with the Inverse Adding Doubling method. Our results
      suggested that within the 400-nm to 850-nm spectrum, optical properties of the
      ground tissue approximated intact tissue within limits of experimental error.

PMID- 21102872
TI  - Time-resolved imaging on a realistic tissue phantom: MU(s)' and MU(a) images
      versus time-integrated images.
AB  - A method is proposed by which we construct images through turbid media, plotting
      directly either the transport-scattering coefficient MU(s) ' or the absorption
      coefficient MU(a). These optical parameters are obtained from the best fit of the
      time-resolved transmittance curves with a diffusion model. Measurements were
      performed with a time-correlated single-photon counting system on realistic
      tissue phantoms simulating a tumor mass within a breast. Images were obtained
      with an incident power of <1 mW and an acquisition time of 1 s/point. Comparison
      of MU(s) ' and MU(a) images with time-integrated images constructed from the same
      experimental data shows that the fitting method discriminates between scattering
      and absorption inhomogeneities and improves image quality for scattering but not
      for absorption inhomogeneities.

PMID- 21102873
TI  - Probabilistic model of multiple light scattering based on rigorous computation of
      the first and the second moments of photon coordinates.
AB  - We consider a concise method based on recurrent relations that permit rigorous
      computing of the first and the second moments of the components of the vector
      locating a randomly walking photon in an infinite homogeneous light-scattering
      medium. On assumption that the components obey a three-dimensional Gaussian
      distribution a probability density for the photon locations at the Nth scattering
      event can readily be written down and the light-intensity distribution in the
      medium may be calculated. The results from theoretical analyses are compared with
      the solution of a light-diffusion equation and with results of Monte Carlo
      simulations and show a better fit with simulated data than the diffusion
      approximation.

PMID- 21102874
TI  - Harmonic and intermodulation performance of spatial light modulators.
AB  - A Fourier-series model describing the nonlinear characteristic of a spatial light
      modulator is presented. With the use of this model, closed-form expressions are
      obtained for the harmonic and intermodulation performance of a spatial light
      modulator excited by a multisinusoidal input-write light intensity.

PMID- 21102875
TI  - Full-range, continuous, complex modulation by the use of two coupled-mode liquid
      crystal televisions.
AB  - Switchable, continuous, complex-amplitude modulation is demonstrated with two
      cascaded, twisted nematic liquid-crystal televisions (LCTV's), both operating in
      phase- and amplitude-coupled modulation modes. The condition for full-range
      complex modulation is that one of the LCTV's must provide a 2pi-range phase
      modulation. A look-up table encoding method is proposed that permits the
      compensation of phase-amplitude coupling and nonlinearity in the two individual
      LCTV modulations. Experimental techniques for determining the LCTV-device
      parameters, for maximizing the phase-mostly modulation range and the amplitude
      mostly modulation contrast, and for testing the complex-amplitude modulation are
      developed. Optical complex-amplitude Fresnel holograms are shown.

PMID- 21102876
TI  - Liquid-crystal projection image depixelization by spatial phase scrambling.
AB  - A technique that removes the pixel structure by scrambling the relative phases
      among multiple spatial spectra is described. Because of the pixel structure of
      the liquid-crystal-display (LCD) panel, multiple spectra are generated at the
      Fourier-spectrum plane (usually at the back focal plane of the imaging lens). A
      transparent phase mask is placed at the Fourier-spectrum plane such that each
      spectral order is modulated by one of the subareas of the phase mask, and the
      phase delay resulting from each pair of subareas is longer than the coherent
      length of the light source, which is approximately 1 MUm for the wideband white
      light sources used in most of LCD's. Such a phase-scrambling technique eliminates
      the coherence between different spectral orders; therefore, the reconstructed
      images from the multiple spectra will superimpose incoherently, and the pixel
      structure will not be observed in the projection image.

PMID- 21102877
TI  - Reconstruction of a vibrating object from its time-averaged image intensities by
      the use of exponential filtering.
AB  - We consider the reconstruction of a complex-valued object that vibrates in some
      out-of-plane modes. The reconstruction is based on the phase-retrieval method
      with the use of two intensity measurements: the two time-averaged image
      intensities of the object illuminated coherently, which are modulated in two
      Fourier-transform planes of the object by the use of two filters with
      exponentially decaying transmittances that complement each other. We discuss the
      necessary condition of the vibration for the reconstruction method. Computer
      simulated examples of retrieving the phases of one-dimensional objects
      demonstrate that the reconstruction of a sinusoidal-vibrating and a Gaussian
      random-vibrating object can be treated by this method.

PMID- 21102878
TI  - Nonlinear cascaded correlation processes to improve the performances of automatic
      spatial-frequency-selective filters in pattern recognition.
AB  - A recognition process consisting of two cascaded correlation stages with a
      sigmoid nonlinearity applied in the first correlation plane is investigated. The
      filters are computed to give prespecified central correlation amplitudes in the
      second correlation plane when inputs are reference images. It is also desired
      that the second correlation amplitudes with the training images should minimize
      the cost function of the automatic spatial-frequency selection algorithm to
      reduce distortion sensitivity and to improve the performance of the filters.
      Filter computation methods are given, and it is shown why two such correlation
      processes may improve the correlation performance. Numerical simulations are
      described and compared with the one-stage correlation system that works with the
      automatic spatial-frequency selection filter.

PMID- 21102879
TI  - Neural-network classifiers for automatic real-world aerial image recognition.
AB  - We describe the application of the multilayer perceptron (MLP) network and a
      version of the adaptive resonance theory version 2-A (ART 2-A) network to the
      problem of automatic aerial image recognition (AAIR). The classification of
      aerial images, independent of their positions and orientations, is required for
      automatic tracking and target recognition. Invariance is achieved by the use of
      different invariant feature spaces in combination with supervised and
      unsupervised neural networks. The performance of neural-network-based classifiers
      in conjunction with several types of invariant AAIR global features, such as the
      Fourier-transform space, Zernike moments, central moments, and polar transforms,
      are examined. The advantages of this approach are discussed. The performance of
      the MLP network is compared with that of a classical correlator. The MLP neural
      network correlator outperformed the binary phase-only filter (BPOF) correlator.
      It was found that the ART 2-A distinguished itself with its speed and its low
      number of required training vectors. However, only the MLP classifier was able to
      deal with a combination of shift and rotation geometric distortions.

PMID- 21102880
TI  - Extracting one-dimensional wavelet features with a diffractive optical inner
      product transform.
AB  - A diffractive optical element (DOE) that performs a wavelet transform on one
      dimensional signals is presented. The DOE performs an inner product between the
      input image and a set of wavelet basis functions. The input image is displayed in
      a spatial light modulator. It is constructed from a one-dimensional signal that
      is spread over the second dimension. Simulated results obtained by the use of
      elementary one-dimensional signals are presented.

PMID- 21102881
TI  - Design and fabrication of computer-generated beam-shaping holograms.
AB  - For the design of computer-generated holograms reconstructing certain intensity
      patterns with phase freedom, we use an object-oriented approach. The given
      intensity pattern is decomposed into elementary objects for which appropriate
      phase-only hologram functions can be constructed. The total hologram function is
      found by the subsequent superposition of its constituents, with a relative
      amplitude and phase weighting for each of them. Thus, the degrees of freedom are
      dramatically reduced compared with those of sampling approaches. The design
      algorithm allows us to compensate on the one hand for the intensity and phase
      distribution of the impinging laser beam and on the other hand for the shape of
      the hologram aperture. We report on the computer-aided design of such holograms,
      as well as their fabrication through the use of laser lithography and reactive
      ion etching. Optical reconstructions are shown.

PMID- 21102882
TI  - Photoinduced anisotropy measurements in liquid-crystalline azobenzene side-chain
      polyesters.
AB  - Reversible photoinduced anisotropy in a series of liquid-crystalline azobenzene
      side-chain polyesters is investigated as a function of intensity of the write
      beam and the sample temperature. Measurements reveal that the erasing takes place
      at a temperature much higher than the glass transition temperature. Induced
      anisotropy can be erased by heating the polyesters to approximately 80  degrees
      C.

PMID- 21102883
TI  - Fractional Radon transform: definition.
AB  - In this paper a novel fractional transformation for which we coin the term the
      fractional Radon transform is defined. This transform generalizes the Radon
      transform and combines it with the fractional Fourier transform. Both
      transformations are useful tools for invariant pattern recognition, tomography,
      and signal processing. Some of the properties of the new transformation, as well
      as further directions for investigation, are presented.

PMID- 21102884
TI  - Programmable spatial filtering with bacteriorhodopsin.
AB  - We describe a programmable spatial-filtering system using bacteriorhodopsin (BR)
      film as a programmable, optically addressed spatial light modulator illuminated
      by a single wavelength of light. We use a computer-controlled mirror scanning
      system to write time-varying filter functions to the BR film and present proof-of
      principle experimental results that demonstrate several elementary filtering
      operations.

PMID- 21102885
TI  - Photonic page buffer based on GaAs multiple-quantum-well modulators bonded
      directly over active silicon complementary-metal-oxide-semiconductor (CMOS)
      circuits: errata.
AB  - Owing to printing errors, [Appl. Opt. 35, 2439 (1996)] several figures were
      illegible. The figures are reprinted and briefly reviewed.

PMID- 21102886
TI  - Dynamic digital photorefractive memory for optoelectronic neural network learning
      modules.
AB  - Neural network modules based on page-oriented dynamic digital photorefractive
      memory are described. The modules can implement two different interconnection
      organizations, fan-out and fan-in, depending on their target network
      applications. Neural network learning is realized by the real-time memory update
      of dynamic digital photorefractive memory. Physical separation of subvolumes in
      the page-oriented photorefractive memory architecture contributes to the low
      cross talk and high diffraction efficiency of the stored interconnection weights.
      Digitally encoded interconnection weights ensure high accuracy, providing
      superior neural network system scalability. Module scalability and feedforward
      throughput have been investigated based on photorefractive memory geometry and
      the photodetector power requirements. The following four approaches to extend
      module scalability are discussed: partial optical summation, semiparallel
      feedforward operation, time partitioning, and interconnection matrix
      partitioning. Learning capabilities of the system are investigated in terms of
      required interconnection primitives for implementing learning processes and three
      memory-update schemes. The experimental results of Perceptron learning network
      implementation with 900 input neurons with digital 6-bit accuracy are reported.

PMID- 21102887
TI  - 64-channel correlator implementing a Kohonen-like neural network for handwritten
      digit recognition.
AB  - We present an optical implementation of an improved version of the Kohonen map
      neural network applied to the recognition of handwritten digits taken from a
      postal code database. Improvements result from the introduction of supervision
      during the learning stage, a technique that also simplifies the map layer
      labeling. The experimental implementation is based on a frequency-multiplexed
      raster computer-generated hologram used to realize the required N(4)
      interconnection. The setup is shown to be equivalent to a 64-channel correlator.
      Computer simulations are used to study various detection and classification
      procedures. The results of the optical experiments, obtained with binary phase
      computer-generated holograms, are presented and shown to be in excellent
      agreement with the simulations.

PMID- 21102888
TI  - Dispersion equations for nonlinear optical crystals: KDP, AgGaSe(2), and
      AgGaS(2).
AB  - A method that uses improved mathematical forms and data-processing techniques has
      been developed for generating index dispersion equations for nonlinear optical
      crystals. The data may be diverse, including measured indices of refraction, type
      I, II, or III critically phase-matched angles, noncritically phase-matched
      wavelengths, non-phase-matched coherence lengths, isoindex wavelengths, and
      optical retrace wavelengths and angles. The method automatically estimates and
      compensates for heretofore unknown crystal orientation errors, attributed
      principally to manufacturing inaccuracies. In the examples given here, 13
      parameter fits to refractive indices n(o) and n(e) are required to reconcile
      literature data(0.49-12 MUm) for AgGaS(2), whereas ten-parameter fits are
      required for KDP (0.18-1.5 MUm) and AgGaSe(2) (0.8-15.5 MUm). These examples
      demonstrate improvements in precision over a wider wavelength range than those
      for previously calculated refractive indices and critically phase-matched angles,
      as well as non-critically phase-matched and isoindex wavelengths.

PMID- 21102889
TI  - Liquid detection with InGaAsP semiconductor lasers having multiple short external
      cavities.
AB  - A liquid detection system consisting of a diode laser with multiple short
      external cavities (MSXC's) is reported. The MSXC diode laser operates single mode
      on one of 18 distinct modes that span a range of 72 nm. We selected the modes by
      setting the length of one of the external cavities using a piezoelectric
      positioner. One can measure the transmission through cells by modulating the
      injection current at audio frequencies and using phase-sensitive detection to
      reject the ambient light and reduce 1/f noise. A method to determine regions of
      single-mode operation by the rms of the output of the laser is described. The
      transmission data were processed by multivariate calibration techniques, i.e.,
      partial least squares and principal component regression. Water concentration in
      acetone was used to demonstrate the performance of the system. A correlation
      coefficient of R(2) = 0.997 and 0.29% root-mean-square error of prediction are
      found for water concentration over the range of 2-19%.

PMID- 21102890
TI  - Explosives detection with a frequency modulation spectrometer.
AB  - An explosives detection instrument was designed and tested at SRI International.
      The instrument uses frequency modulation spectroscopy with midinfrared lead-salt
      diode lasers to perform high-sensitivity detection of characteristic nitrogen
      containing decomposition products of explosives. Ultimately, the instrument
      should be capable of detecting and identifying subpicogram levels of plastic
      explosives, which would be suitable for screening passengers at airports. Using
      the laboratory breadboard instrument and two different explosive vapor
      generators, we demonstrated a lower limit of detection of 5-10 pg for
      cyclotrimethylene trinitramine and linearity of the signal over an order of
      magnitude.

PMID- 21102891
TI  - Two-tone frequency-modulation spectroscopy for quantitative measurements of
      gaseous species: theoretical, numerical, and experimental investigation of line
      shapes.
AB  - The capability of retrieving spectral information from line shapes recorded by
      two-tone frequency-modulation spectroscopy (TTFMS) is investigated. A TTFMS
      theory accounting for dispersion and nonlinear distortion of diode laser
      frequency modulation response is presented. The adequacy of the theory for a
      detailed modeling of line shapes recorded with high resolution is examined. An
      extensive error analysis of line parameters (i.e., width, intensity, and line
      center) retrieved by a nonlinear least-squares fitting procedure is made. Plots
      of residual errors with characteristic signatures that are due to incorrectly
      assigned modulation parameters and choice of line profile are presented. In least
      squares fits to experimental oxygen data with a Voigt profile influence from
      collisional(Dicke) narrowing is clearly exhibited, and when we used a
      collisionally narrowed line profile deviations of the model were reduced to less
      than 0.2%. We demonstrate that accurate quantitative measurements by TTFMS over a
      wide range of concentrations, temperatures, and pressures are possible.

PMID- 21102892
TI  - Experimental investigation of the self- and N(2)-broadened continuum within the
      nu(2) band of water vapor.
AB  - We present an experimental study of the self- and N(2)-broadened H(2) O continuum
      in microwindows within the nu(2) fundamental centered at ~1600 cm(-1). The
      continuum is derived from transmission spectra recorded at room temperature with
      a BOMEM Fourier transform spectrometer at a resolution of ~0.040 cm(-1). Although
      we find general agreement with previous studies, our results suggest that there
      is significant near-wing super-Lorentzian behavior that produces a highly wave
      number-dependent structure in the continuum as it is currently defined.

PMID- 21102893
TI  - Two-tone frequency modulation spectroscopy from laser light scattered off a hard
      target.
AB  - One can apply two-tone frequency modulation spectroscopy techniques to the
      detection of gas-phase species by using laser light scattered from hard targets.
      High sensitivities are demonstrated, with a minimum detectable absorption of 10(
      4) possible with a simple apparatus. The effects of laser speckle on the FM
      signal are described, and we show that the detection signal-to-noise ratio can be
      improved by collecting an increased number of speckle cells.

PMID- 21102894
TI  - Optical performance of a burst-mode multikilowatt CO(2) laser.
AB  - A unique advancement in the flexibility of high-power lasers is presented.
      Operation of a 20-kW, continuous-wave, CO(2) laser with a burst excitation
      technique produces a broad range of optical output characteristics. A detailed
      discussion of the discharge excitation of this system demonstrates some unique
      features of the process. Control of burst frequency and duty cycle provides a
      convenient means to alter the time-varying nature of the output beam. Laser
      output can be varied from distinct, independent pulses through to a continuous
      wave. Optical pulse shape varies from triangular to square in profile. The
      primary focus of this study lies in the regime with distinct, separate pulses.
      Empirical relationships that summarize the dependence of optical duty cycle and
      peak laser power on discharge control parameters are developed. Use of these
      relations imparts control of the optical parameters of importance in deep
      penetration welding.

PMID- 21102895
TI  - Near shot-noise-level relative frequency stabilization of a laser-diode-pumped
      Nd:YVO(4) microchip laser.
AB  - A laser-diode-pumped Nd:YVO(4) microchip laser was built and actively frequency
      stabilized relative to a Fabry-Perot cavity with the frequency-modulated sideband
      technique. The error signal reaches the shot-noise level of 7.4 mHz/?Hz around 1
      kHz. Excess intensity noise sets a lower limit of16.5 mHz/?Hz for the relative
      frequency noise, corresponding to a spectral linewidth of 860 MUHz. We discuss
      the method for reconstructing the actual frequency deviation from the observed
      error signal.

PMID- 21102896
TI  - Flash-lamp-excited self-injection-seeded Q-switched Ti:Al(2)O(3) laser
      oscillator.
AB  - A self-injection-seeded, flash-lamp-excited, Q-switched laser oscillator is
      presented. The laser comprises two resonators that are operated sequentially. The
      first resonator, which includes all the high insertion loss, damage prone,
      wavelength tuning, and line-narrowing components, is used to generate the seed
      signal. The second resonator is a low-loss, Q-switched resonator whose output
      wavelength and line width are controlled by the seed signal. Output pulses of
      energy as high as 325 mJ have been obtained that are tunable over a range of the
      order of 90 nm and with a bandwidth of the order of 0.05 nm.

PMID- 21102897
TI  - Fluorescence and phase-conjugated signals of organic materials: erratum.

PMID- 21102898
TI  - Experimental verification of analytic modeling of erbium-doped silica fiber
      amplifiers pumped at 1480 nm.
AB  - Gain measurements are carried out for different lengths of three types of erbium
      doped silica fiber with different pump powers at 1480 nm. From these measurements
      a relation is established for each type of fiber between gain and the attenuation
      factor of the pump power. This relation is in complete agreement with the one
      predicted by an analytic model based on overlapping factors, which makes it
      possible to obtain methods for the experimental characterization of doped fibers.

PMID- 21102899
TI  - Kronig-Penney model for periodically segmented waveguides.
AB  - Physical insight into the propagation characteristics of periodically segmented
      waveguides can be obtained by viewing the guiding layer as a thin slab of an
      idealized infinite medium with periodic layers along the direction of
      propagation. One can analyze the properties of this infinite medium using a
      formal analogy with the Kronig-Penney model used to describe the propagation of
      electron wave functions in a periodic crystal potential. The model correctly
      gives the effective refractive index of the layer, gives insight into the
      electric field profiles at different points on the dispersion curve, and leads to
      a qualitative explanation of why the optical loss diminishes at both large and
      small duty cycles.

PMID- 21102900
TI  - Birefringent properties of diametrically loaded gradient-index lenses.
AB  - Gradient-index (GRIN) lenses have been widely used as collimators in various
      fiber-optic sensors and as optical coupling devices in components designed for
      optical communication systems. However, relatively little attention has been paid
      to the birefringent properties of GRIN lenses and the potential for using them as
      photoelastic sensing elements in optical transducers. Analytical and experimental
      results are described that were obtained for the intensity distribution produced
      by studying a GRIN lens by using a polariscope. The residual birefringence
      inherent in an unloaded lens is initially studied. The lens is then assumed to be
      diametrically loaded and the superposition is studied by the method of ray
      tracing. When the results obtained from the simulation for a Selfoc, 0.25-pitch
      lens are compared with experimental data, an excellent agreement is obtained.
      Intensity increases monotonically with load, confirming that the lens would be a
      good choice for the sensing element of an optical transducer designed as part of
      a strain or acceleration measurement system. The numerical simulation is then
      used to study the influence of residual stress on sensitivity.

PMID- 21102901
TI  - Laser interferometric diffractometry for measurements of diffraction grating
      spacing.
AB  - Two methods and an experimental setup for the measurement of spacing of
      diffraction gratings have been developed. These methods depend on interferometric
      measurements at different wavelengths of the angles of diffraction beams from the
      grating to be measured. A lower limit for the measured spacing is the half
      wavelength of laser radiation. The results of spacing measurements of
      approximately 0.28, 0.39, and 0.50 MUm are presented.

PMID- 21102902
TI  - Thermal effects in a hollow waveguide beam launch for CO(2) laser power delivery.
AB  - Thermal effects caused by launching conditions in a CO(2) laser beam delivery
      that uses metallic hollow waveguides is investigated. It is found that front-end
      clipping is the main cause of thermal loading and generates a steep temperature
      gradient at the fiber front end while the continuous beam attenuation produces a
      temperature distribution declining slowly along the waveguide.

PMID- 21102903
TI  - Compensational three-wavelength differential-absorption lidar technique for
      reducing the influence of differential scattering on ozone-concentration
      measurements.
AB  - A three-wavelength differential-absorption lidar (DIAL) technique for the
      ultraviolet spectral region is presented that reduces the influence of aerosol
      differential scattering on measured ozone-concentration profiles. The principal
      advantage of this approach is that, to a good first approximation, no correction
      for aerosol differential-extinction and backscattering effects are needed.
      Therefore, one avoids having to obtain an aerosol extinction-coefficient profile
      at a reference wavelength; nor does one have to invoke questionable assumptions
      regarding the spectral dependence of the aerosol total and backscatter
      coefficients.

PMID- 21102904
TI  - Reduction of the pulse spike-cut error in Fourier-deconvolved lidar profiles.
AB  - A simple approach is analyzed and applied to the National Oceanic and Atmospheric
      Administration (NOAA) Doppler lidar data to reduce the error in Fourier
      deconvolved lidar profiles that is caused by spike-cut uncertainty in the laser
      pulse shape, i.e., uncertainty of the type of not well-recorded (cut, missed)
      pulse spikes. Such a type of uncertainty is intrinsic to the case of TE (TEA)
      CO(2) laser transmitters. This approach requires only an estimate of the spike
      area to be known. The result from the analytical estimation of error reduction is
      in agreement with the results from the NOAA lidar data processing and from
      computer simulation.

PMID- 21102905
TI  - Nonlinear-approximation technique for determining vertical ozone-concentration
      profiles with a differential-absorption lidar.
AB  - A new technique is presented for the retrieval of ozone-concentration profiles
      (O(3)) from backscattered signals obtained by a multiwavelength differential
      absorption lidar (DIAL). The technique makes it possible to reduce erroneous
      local fluctuations induced in the ozone-concentration profiles by signal noise
      and other phenomena such as aerosol inhomogeneity. Before the O(3) profiles are
      derived, the dominant measurement errors are estimated and uncertainty boundaries
      for the measured profiles are established. The off- to on-line signal ratio is
      transformed into an intermediate function, and analytical approximations of the
      function are then determined. The separation of low- and high-frequency
      constituents of the measured ozone profile is made by the application of
      different approximation fits to appropriate intermediate functions. The low
      frequency constituents are approximated with a low-order polynomial fit, whereas
      the high-frequency constituents are approximated with a trigonometric fit. The
      latter fit makes it possible to correct the measured O(3) profiles in zones of
      large ozone-concentration gradients where the low-order polynomial fit is found
      to be insufficient. Application of this technique to experimental data obtained
      in the lower troposphere shows that erroneous fluctuations induced in the ozone
      concentration profile by signal noise and aerosol inhomogeneity undergo a
      significant reduction in comparison with the results from the conventional
      technique based on straightforward numerical differentiation.

PMID- 21102906
TI  - Lidar aerosol backscatter cross sections in the 2-num near-infrared wavelength
      region.
AB  - Lidar backscatter cross-sectional measurements at 1.064, 0.532, and 1.54 MUm were
      acquired during November 1989 and May-June 1990 around the Pacific region by the
      NASA DC-8 aircraft as part of the Global Backscatter Experiment. The primary
      motivation for the Global Backscatter Experiment was the study of lidar
      backscatter cross sections for the development of a spaceborne wind-sensing
      lidar. Direct backscatter measurements obtained by the NASA Goddard Space Flight
      Center visible and infrared lidar are compared with backscatter cross sections
      calculated from aerosol size distributions obtained by particle counters. Results
      for one flight with pronounced aerosol layers in the upper troposphere southeast
      of Japan are presented. Because 2-MUm region wavelengths are possible candidates
      for a spaceborne wind-sensing lidar, the visible and infrared lidar backscatter
      cross sections at 1.064, 0.532, and 1.54 MUm are extrapolated to the 2-MUm
      region. The extrapolated 2-MUm cross sections are compared with lidar
      measurements at 9 MUm. A significant range in the ratio of 2-9-MUm backscatter
      cross sections is found, but a large number of points concentrate near ratios of
      three to ten. A large number of 1.064- and 1.54-MUm cross sections were binned to
      provide an estimate of backscatter for various percentiles for the flight. The
      ratio of the 50-percentile backscatter values at 1.064 and 1.54 MUm suggest a
      lambda(-1.9) to lambda(-3.0) wavelength dependence of aerosol backscatter cross
      section in the near infrared for the observational case.

PMID- 21102907
TI  - Optimization of coherent lidar performance with graded-reflectance transmitter
      resonator optics in the low equivalent Fresnel number regime.
AB  - Using a diffractive eigenmode treatment to model the laser output we show that
      graded-reflectance resonator optics offer significant efficiency benefits over
      conventional hard-edge coupled unstable resonators in the context of coherent
      detection lidar applications. Extending previous research pertinent to the high
      equivalent Fresnel number regime, we have modeled the optimum performance of a
      notional super-Gaussian coupled cavity as a function of the key resonator
      parameters in the low equivalent Fresnel number (<3) regime. The findings from
      this study are applicable to the design of coherent lidar transmitters operated
      within this regime.

PMID- 21102908
TI  - Directional reflectance characterization facility and measurement methodology.
AB  - A precision reflectance characterization facility, constructed specifically for
      the measurement of the bidirectional reflectance properties of Spectralon panels
      planned for use as in-flight calibrators on the NASA Multiangle Imaging
      Spectroradiometer (MISR) instrument is described. The incident linearly polarized
      radiation is provided at three laser wavelengths: 442, 632.8, and 859.9 nm. Each
      beam is collimated when incident on the Spectralon. The illuminated area of the
      panel is viewed with a silicon photodetector that revolves around the panel (360
      degrees ) on a 30-cm boom extending from a common rotational axis. The reflected
      radiance detector signal is ratioed with the signal from a reference detector to
      minimize the effect of amplitude instabilities in the laser sources. This and
      other measures adopted to reduce noise have resulted in a bidirectional
      reflection function (BRF) calibration facility with a measurement precision with
      regard to a BRF measurement of +/-0.002 at the 1sigma confidence level. The
      Spectralon test piece panel is held in a computer-controlled three-axis
      rotational assembly capable of a full 360 degrees  rotation in the horizontal
      plane and 90 degrees  in the vertical. The angular positioning system has
      repeatability and resolution of 0.001 degrees . Design details and an outline of
      the measurement methodology are presented.

PMID- 21102909
TI  - Information content of the spectral transmittance of the marine atmospheric
      boundary layer.
AB  - We developed a procedure for using data for attenuation sigma of the marine
      atmosphere at lambda = 0.55 MUm and Angstrom parameter alpha in the visible range
      for the estimation of aerosol particle size spectrum. We evaluated the aerosol
      microstructure in the marine atmospheric boundary layer (MABL). To eliminate the
      effect of the upper troposphere and stratosphere, we assumed that the optical
      characteristics of the microstructure are average for the typical marine
      atmosphere. The sought-for MABL microstructure is parameterized by the sum of two
      fractions, each having a log-normal distribution (the fine and large components).
      The problem amounts to determining six unknown parameters from two
      characteristics. In accordance with experimental data as well as with theoretical
      aerosol models, the total particle concentration n and the fraction of the large
      component c(2) are assumed to be constant for the central regions of the world
      ocean. In this way, the problem can be reduced to the determination of the
      acceptable value area of the remaining four parameters. For all models situated
      in this area, values of sigma and alpha fall within some intervals Deltasigma and
      Deltaalpha, specific for each aerosol type. Since the problem is ambiguous, the
      number of models comprising an acceptable ensemble is great. So this number is
      equal to 5972 in the example that illustrates our procedure. It is noteworthy,
      however, that all the models entering the ensembles have a similar microstructure
      within the active radius interval of 0.02-3 MUm, which is the main interval that
      governs the transmittance in the 0.3-1 MUm spectral range. The average curve that
      can be plotted for the entire ensemble can be used as a solution to the problem,
      which is the main result of this study. We are also concerned with how aerosol
      transmittance measurements in one of the infrared channels could be used to
      diminish the ambiguity of the problem. The answer depends on the specific aerosol
      structure. In most cases, additional IR data in one channel barely decreases the
      ambiguity of the problem. However, such data might be useful for some other
      distributions. We consider the effect of six IR channels in our example.

PMID- 21102910
TI  - Underwater vehicles equipped with laser beacons and tracked from aircraft.
AB  - The successful results of a feasibility experiment for tracking underwater
      vehicles equipped with laser beacons by aircraft equipped with detectors are
      presented. The system design focuses on tracking limited payload vehicles such as
      torpedoes in shallow-water (0-200 m) environments during Navy test and evaluation
      exercises. A compact, battery operated, Q-switched, frequency-doubled, dual-pulse
      Nd:YAG laser operating at 532 nm was used. The upward-pointing laser with a
      diffuse 14 degrees  output beam was mounted to a stationary buoy at a depth of
      five attenuation lengths. Aboard an SH3 helicopter at 5000 ft (1524 m), a 14
      degrees  field-of-view avalanche photodiode detector system detected the first
      pulse that triggered an image-intensified CCD camera to image the second pulse at
      the ocean surface. When the results were scaled, we concluded that a coverage
      diameter of 14,375 m could be achieved at an aircraft elevation of 1 mile (1.6
      km) with a signal-to-noise ratio of 10:1 for depths of ten attenuation lengths.

PMID- 21102911
TI  - Diffuse reflectance of oceanic waters. III. Implication of bidirectionality for
      the remote-sensing problem.
AB  - The upwelling radiance field beneath the ocean surface and the emerging radiance
      field are not generally isotropic. Their bidirectional structure depends on the
      illumination conditions (the Sun's position in particular) and on the optical
      properties of the water body. In oceanic case 1 waters, these properties can be
      related, for each wavelength lambda, to the chlorophyll (Chl) concentration. We
      aim to quantify systematically the variations of spectral radiances that emerge
      from an ocean with varying Chl when we change the geometric conditions, namely,
      the zenith-Sun angle, the viewing angle, and the azimuth difference between the
      solar and observational vertical planes. The consequences of these important
      variations on the interpretation of marine signals, as detected by a
      satelliteborne ocean color sensor, are analyzed. In particular, the derivation of
      radiometric quantities, such as R (lambda), the spectral reflectance, or [
      L(w)(lambda)](N), the normalized water-leaving radiance that is free from
      directional effects, is examined, as well as the retrieval of Chl. We propose a
      practical method that is based on the use of precomputed lookup tables to provide
      values of the f/Q ratio in all the necessary conditions[ f relates (R(lambda) to
      the backscattering and absorption coefficients, whereas Q is the ratio of
      upwelling irradiance to any upwelling radiance]. The f/Q ratio, besides being
      dependent on the geometric configuration (the three angles mentioned above), also
      varies with lambda and with the bio-optical state, conveniently depicted by Chl.
      Because Chl is one of the entries for the lookup table, it has to be derived at
      the beginning of the process, before the radiometric quantities R(lambda) or
      [L(W)(lambda)](N) can be produced. The determination of Chl can be made through
      an iterative process, computationally fast, using the information at two
      wavelengths. In this attempt to remove the bidirectional effect, the commonly
      accepted view relative to the data-processing strategy is somewhat modified,
      i.e., reversed, as the Chl index becomes a prerequisite parameter that must be
      identified prior to the derivation of the fundamental radiometric quantities at
      all wavelengths.

PMID- 21102912
TI  - Measurements and empirical modeling of pure CO(2) absorption in the 2.3-num
      region at room temperature: far wings, allowed and collision-induced bands.
AB  - Measurements of pure CO(2) absorption in the 2.3-MUm region are presented. The
      3800-4700-cm(-1) range has been investigated at room temperature for pressures in
      the 10-50-atm range by using long optical paths. Phenomena that contribute to
      absorption are listed and analyzed, including the contribution of far line wings
      as well as those of the central region of both allowed and collision-induced
      absorption bands. The presence of simultaneous transitions is also discussed.
      Simple and practical approaches are proposed for the modeling of absorption,
      which include a line-shape correction factor chi that extends to approximately
      600 cm(-1) from line centers.

PMID- 21102913
TI  - Elliptical halos, Bottlinger's rings, and the ice-plate snow-star transition.
AB  - Elliptical halos and Bottlinger's rings are simulated by the use of a Monte Carlo
      algorithm that includes multiple scattering. High multiple reflections are
      required to obtain a sufficient brightness of the elliptical halos. By
      introducing three populations of nearly horizontal, gyrating, and swinging
      crystals, we obtain good agreement for four photographs of displays with ringlike
      and disklike structures. Through model experiments on the aerodynamical behavior
      of crystals, we find a new interpretation of the three populations. In this view
      elliptical halos and Bottlinger's rings occur in the transition region of ice
      plates with broad branches and stellar crystals at temperatures near -15  degrees
      C and large supersaturations. This interpretation is supported by a review of 23
      reports of elliptical halo phenomena by members of the Finnish Halo Observers
      Network.

PMID- 21102914
TI  - Statistical anisotropy in free turbulence for mixing layers at high Reynolds
      numbers.
AB  - A lateral shearing interferometer was used to measure the slope of perturbed wave
      fronts after propagating through free turbulent mixing layers. Shearing
      interferometers provide a two-dimensional flow visualization that is
      nonintrusive. Slope measurements were used to reconstruct the phase of the
      turbulence-corrupted wave front. The random phase fluctuations induced by the
      mixing layer were captured in a large ensemble of wave-front measurements.
      Experiments were performed on an unbounded, plane shear mixing layer of helium
      and nitrogen gas at fixed velocities and high Reynolds numbers for six locations
      in the flow development. Statistical autocorrelation functions and structure
      functions were computed on the reconstructed phase maps. The autocorrelation
      function results indicated that the turbulence-induced phase fluctuations were
      not wide-sense stationary. The structure functions exhibited statistical
      homogeneity, indicating that the phase fluctuations were stationary in first
      increments. However, the turbulence-corrupted phase was not isotropic. A five
      thirds power law is shown to fit orthogonal slices of the structure function,
      analogous to the Kolmogorov model for isotropic turbulence. Strehl ratios were
      computed from the phase structure functions and compared with classical estimates
      that assume isotropy. The isotropic models are shown to overestimate the optical
      degradation by nearly 3 orders of magnitude compared with the structure function
      calculations.

PMID- 21102915
TI  - Experimental assessment of O(2) interferences on laser-induced fluorescence
      measurements of NO in high-pressure, lean premixed flames by use of narrow-band
      and broadband detection.
AB  - We experimentally investigate the influence of O(2) interferences on laser
      induced fluorescence measurements of NO in lean methane-fueled flames at a range
      of pressures for both narrow-band and broadband fluorescence detection. We
      identify NO excitation schemes that minimize O(2) interferences. From detection
      scans we obtain interference spectra for the different NO excitation schemes. We
      then identify optimum excitation-detection schemes for narrow-band detection
      measurements of NO. To simulate broadband detection experiments, we numerically
      apply five different filter combinations to the experimentally obtained detection
      scans. We develop filter-assessment parameters to judge the effectiveness of the
      different filtering schemes, and we establish a methodology for evaluating
      broadband excitation-detection strategies. From this research we identify optimum
      excitation-detection schemes for broadband detection measurements of NO.

PMID- 21102916
TI  - Diode laser-based air mass flux sensor for subsonic aeropropulsion inlets.
AB  - An optical air mass flux sensor based on a compact, room-temperature diode laser
      in a fiber-coupled delivery system has been tested on a full-scale gas turbine
      engine. The sensor is based on simultaneous measurements of O(2) density and
      Doppler-shifted velocity along a line of sight across the inlet duct. Extensive
      tests spanning engine power levels from idle to full afterburner demonstrate
      accuracy and precision of the order of 1-2% of full scale in density, velocity,
      and mass flux. The precision-limited velocity at atmospheric pressure was as low
      as 40 cm/s. Multiple data-reduction procedures are quantitatively compared to
      suggest optimal strategies for flight sensor packages.

PMID- 21102917
TI  - Stark broadening corrections to laser-induced fluorescence temperature
      measurements in a hydrogen arcjet plume.
AB  - Laser-induced fluorescence of the H(alpha) transition of atomic hydrogen has
      previously been performed in the plume of a hydrogen arcjet thruster.
      Measurements of plasma velocity and temperature, based on the Doppler shift and
      broadening of the H(alpha) line shape, were previously published [Appl. Opt. 32,
      6117 (1993)]. In that paper the Stark broadening of the H(alpha) transition was
      estimated from static-ion calculations performed in the early 1970's and found to
      be negligible in comparison with the Doppler broadening. However, more recent
      dynamic-ion calculations have shown the Stark broadening to be considerably
      larger than was previously assumed, resulting in inaccurate temperature
      measurements. We present a reanalysis of the fluorescence data, taking into
      account the improved Stark broadening calculations. The correct atomic hydrogen
      translation temperature and electron number density are obtained from the Doppler
      and Stark broadening components of the measured line shape. The results indicate
      a substantial drop in temperature from those previously reported.

PMID- 21102918
TI  - High-resolution size measurement of single spherical particles with a fast
      Fourier transform of the angular scattering intensity.
AB  - A technique is described and demonstrated to measure the size of spherical
      particles of known index of refraction by laser light scattering with an accuracy
      of better than 1%. This technique entails imaging the angular scattering
      intensity onto a photodiode array and applying a fast Fourier transform to the
      array output to obtain a frequency and phase corresponding to the number and
      angular position of the scattering lobes. Errors associated with particle
      trajectory effects and changes in the index of refraction are also considered.
      Results are not affected by the former, whereas variations of the refractive
      index by 2%, as may be typical, for example, of the transient heat up of a liquid
      hydrocarbon droplet, cause a deterioration of sizing accuracy to approximately
      3%. The technique can in principle be applied in real time at data rates as high
      as 20-30 kHz with a modest equipment investment. Therefore, the measurement of
      droplet evaporation rates in dilute sprays with unprecedented accuracy appears to
      be feasible.

PMID- 21102919
TI  - Scattering of light by polydisperse, randomly oriented, finite circular
      cylinders.
AB  - We use the T-matrix method, as described by Mishchenko [Appl. Opt. 32, 4652
      (1993)], to compute rigorously light scattering by finite circular cylinders in
      random orientation. First we discuss numerical aspects of T -matrix computations
      specific for finite cylinders and present results of benchmark computations for a
      simple cylinder model. Then we report results of extensive computations for
      polydisperse, randomly oriented cylinders with a refractive index of 1.53 +
      0.008i, diameter-to-length ratios of 1/2, 1/1.4, 1, 1.4, and 2, and effective
      size parameters ranging from 0 to 25. These computations parallel our recent
      study of light scattering by polydisperse, randomly oriented spheroids and are
      used to compare scattering properties of the two classes of simple convex
      particles. Despite the significant difference in shape between the two particle
      types (entirely smooth surface for spheroids and sharp rectangular edges for
      cylinders), the comparison shows rather small differences in the integral
      photometric characteristics (total optical cross sections, single-scattering
      albedo, and asymmetry parameter of the phase function) and the phase function.
      The general patterns of the other elements of the scattering matrix for cylinders
      and aspect-ratio-equivalent spheroids are also qualitatively similar, although
      noticeable quantitative differences can be found in some particular cases. In
      general, cylinders demonstrate much less shape dependence of the elements of the
      scattering matrix than do spheroids. Our computations show that, like spheroids
      and bispheres, cylinders with surface-equivalent radii smaller than a wavelength
      can strongly depolarize backscattered light, thus suggesting that backscattering
      depolarization for nonspherical particles cannot be universally explained by
      using only geometric-optics considerations.

PMID- 21102920
TI  - Tropospheric aerosol extinction coefficient profiles derived from scanning lidar
      measurements over Tsukuba, Japan, from 1990 to 1993.
AB  - Mie scattering lidar was used to observe aerosol extinction coefficient profiles
      in the troposphere over Tsukuba (140 E, 36 N), Japan, for three years from March
      1990 to February 1993, and data obtained in fair weather were analyzed. The lidar
      measurements were made by a vertical scanning mode to generate profiles of
      extinction coefficients from the lidar level to a 12-km altitude. The extinction
      coefficients were derived from the lidar signals using a two-component (air
      molecule and aerosol) lidar equation, in which the ratio of aerosol extinction to
      backscattering was assumed to be constant. Seasonal average profiles were derived
      from individual profiles. Three-year average profiles were also calculated and
      modeled using mathematical expressions. The model profile assumed (1) a constant
      extinction ratio in the atmospheric boundary layer (ABL), (2) an exponentially
      decreasing extinction ratio above the ABL, and (3) a constant extinction ratio in
      the upper troposphere where the extinction ratio can be defined as the ratio of
      the aerosol extinction coefficient to the air molecule extinction coefficient.
      The extinction ratios both in the ABL and in the upper troposphere and the scale
      height that was used to express the exponential decrease were used as three
      unknown parameters. Seasonal variation of optical thickness that was obtained by
      integrating extinction coefficients with height was also investigated.

PMID- 21102921
TI  - Optical interference coatings: introduction by the feature editors.

PMID- 21102923
TI  - Multilayer reflectors with absent higher-order reflectance bands.
AB  - Explicit equations are presented for the refractive indices of all-dielectric
      multilayers that reflect at a longer wavelength and transmit over a broad range
      of shorter wavelengths. Equations are given for the refractive indices of the
      layers of a simulated rugate reflector.

PMID- 21102922
TI  - Design of a hot mirror: contest results.
AB  - Various designs for a hot mirror to improve the efficacy of tungsten lamps are
      described. These designs were solicited at the 1995 Topical Meeting on Optical
      Interference Coatings.

PMID- 21102924
TI  - Estimating the number of layers required and other properties of blocker and
      dichroic optical thin films.
AB  - Empirically derived formulas are given that allow the thin-film designer to
      estimate in advance the number of layers needed to meet various thin-film optical
      performance requirements. The estimation of peak optical density and width of
      higher-order blocker bands and their suppression are also discussed.

PMID- 21102925
TI  - Optical coating without phase dispersion for a Fabry-Perot interferometer.
AB  - Phase dispersion induced by coatings can be a critical phenomenon in
      interferometry. We are interested in special mirrors intended for a Fabry-Perot
      interferometer with a high reflectance region and a low reflectance region in
      which phase dispersion on reflection must be avoided. We describe how a classical
      approach that uses the concepts of admittance and symmetrical multilayers allows
      the design of simple solutions.

PMID- 21102926
TI  - Universal antireflection coatings for substrates for the visible spectral region.
AB  - It is possible to design normal-incidence antireflection coatings that reduce the
      reflectance of any substrate with a refractive index that lies in the range of
      1.48 to 1.75. The performance of such coatings depends on the width of the
      spectral region over which the reflectance is to be suppressed, on the coating
      materials used for their construction, and on the overall optical thickness of
      the layer system. For example, the calculated average spectral reflectance of a
      set of six different substrates with refractive indices 1.48, 1.55, 1.60, 1.65,
      1.70, and 1.75, when coated with a 0.56-MUm-thick, eight-layer antireflection
      coating designed for the 0.40-0.80-MUm spectral region, was 0.34%. This is higher
      than the average reflectance that is attainable with a conventional
      antireflection coating of similar optical thicknesses designed for a particular
      refractive index. However, it is an acceptable value for most applications. With
      the universal type of antireflection coating described, it is thus possible to
      coat a number of different refractive-index substrates in one deposition run, and
      this can result in considerable cost and time savings.

PMID- 21102927
TI  - Infrared ellipsometry investigation of SiO(x)N(y) thin films on silicon.
AB  - The dielectric function ~epsilon (~epsilon = epsilon(1) + iepsilon(2)) of silicon
      oxynitride films deposited on silicon wafers by dual ion-beam sputtering is
      determined by infrared ellipsometry between 580 and 5000 cm(-1). The phase
      separation model is unable to reproduce the experimental data. The dependence of
      ~epsilon on stoichiometry is analyzed with the microscopic Si-centered
      tetrahedron model. The random-bonding model with five SiO(4-j)N(j) (j = 0-4)
      tetrahedra gives a good description of the spectra, provided the dielectric
      function of the mixed tetrahedra is carefully chosen.

PMID- 21102928
TI  - Fluorescence of Ta(2)O(5) thin films doped by kilo-electron-volt Er implantation:
      application to microcavities.
AB  - Luminescent layers are prepared by the implantation of kilo-electron-volt Er ions
      into tantalum pentoxide (Ta(2)O(5)) thin films made by ion plating. The
      implantation fluences range from 3.3 * 10(14) to 2 * 10(15) ions/cm(2), and the
      energies range from 190 to 380 keV. Refractive index, extinction coefficient, and
      losses on guided propagation are investigated. We show that these Er-implanted
      layers present an absorption as low as that of the nonimplanted films. When
      optically pumped with an Ar(+) laser (lambda = 0.488 MUm) beam, implanted films
      show peaked fluorescence spectra centered near 1.53 and 0.532 MUm. We show that
      the fluorescence intensity is correlated with the intensity of the pump beam in
      the region where Er ions are implanted. Radiation patterns of Er ions located
      inside a single layer or inside a Ta(2)O(5)/SiO(2) dielectric stack made by ion
      plating are also investigated. We show that, in any case, spontaneous emission of
      Er ions can be spatially controlled.

PMID- 21102929
TI  - Light-induced refractive-index modifications in dielectric thin films:
      experimental determination of relaxation time and amplitude.
AB  - A two-beam setup based on the totally reflecting prism coupler is shown to be a
      powerful means of characterizing light-induced refractive-index modifications in
      dielectric thin films. Rise and relaxation times and amplitudes of thin-film
      refractive-index variations can be measured. Some developments of the
      electromagnetic theory of prism coupling are presented for Gaussian incident
      beams. Measurements made on a single Ta(2)O(5) layer deposited on a silica glass
      are presented. Relaxation times of a few milliseconds reveal the thermal origin
      of the phenomena. The thermal nonlinear coefficient of this Ta(2)O(5) layer is
      nearly 10(-15) m(2)/W.

PMID- 21102930
TI  - Characterization of optical coatings by photothermal deflection.
AB  - An overview of photothermal deflection principles and applications is given. The
      modeling of temperature distribution and the calculation of deflection that is
      due to both the refractive-index gradient and the thermal deformation of the
      sample are presented. Three configurations usually employed are compared, and
      their respective advantages are discussed in relation to their application. The
      calibration for absolute measurement of absorption is detailed, showing that
      calibration limits the accuracy of measurement. Some examples of specific
      information obtained by photothermal mapping of absorption are given.

PMID- 21102931
TI  - Estimation of optical constants of thin film by the use of artificial neural
      networks.
AB  - A system for analyzing single-layer optical thin films has been formulated by the
      use of artificial neural networks. The training data sets stem from the
      computational results of the physical model of thin films, and they are used to
      train the artificial neural network, which, when done, can give values of film
      parameters in the millisecond time regime. The fast backpropagation algorithm is
      employed during training. The results of training are also given.

PMID- 21102932
TI  - Determination of the refractive index and thickness of transparent pellicles by
      use of the polarization-independent absentee-layer condition.
AB  - The refractive index and the thickness of a transparent pellicle are determined
      when the pellicle is placed between two vertical crossed polarizers and rotated
      in the horizontal plane. The transmission axes of the polarizers are neither
      parallel nor perpendicular to the plane of incidence. The light transmitted
      through the crossed polarizers reaches a minimum when the pellicle satisfies the
      absentee-layer condition. The refractive index and the film thickness are
      obtained from the pellicle orientation angles under such a condition.

PMID- 21102933
TI  - Using surface plasmon resonances to test the durability of silver-copper films.
AB  - Silver has high reflectivity in the visible and infrared but cannot be used fully
      because of its distressing lack of durability. A technique that uses the surface
      plasmon resonance phenomenon offers a sensitive method for studying the corrosion
      of silver and assessing improvements. It has been used in the investigation of
      the effects of flashing a thin layer, approximately 1 nm thick, of copper over
      silver in an attempt at cathodic protection. Tests include exposing silver and
      silver-copper films to air, 94% relative humidity, water, and hydrogen sulfide.

PMID- 21102934
TI  - Determination of grain size in indium tin oxide films from transmission
      measurements.
AB  - The grain size of In(2)O(3):Sn thin films on transparent substrates is
      determined. The method employs the ratio of specular to total transmission to
      deduce the film grain size. Interpretation of these data is accomplished with the
      aid of Bhattacharyya et al.'s model [Vacuum 43, 1201 (1992)] of a polycrystalline
      thin film. This is combined with knowledge of scattering cross-correlation laws.
      Finally, a simple correction is derived for the scattering contribution from the
      substrate. Although approximate, the results for the grain size obtained by the
      reported optical method and by scanning electron microscopy were in agreement
      within experimental uncertainties.

PMID- 21102935
TI  - Combination of surface characterization techniques for investigating optical thin
      film components.
AB  - To meet the requirements of comprehensively characterizing the morphology of thin
      films and substrates, a suitable combination of different measuring techniques
      should be chosen, i.e., a nonoptical surface profile measurement should be used
      together with optical analysis. It is demonstrated on selected examples of
      fluoride and oxide films that the use of atomic force microscopy and light
      scattering fulfills the demand of appropriate quantitative characterization over
      a sufficiently large range of bandwidths.

PMID- 21102936
TI  - Substrate effects on absorption of coated surfaces.
AB  - Photothermal deflection is used for mapping the absorption of bare and coated
      surfaces. The same area is mapped before and after coating and also after
      annealing. The great importance of the substrate with respect to the total losses
      of the coated component is emphasized. First the influence of surface
      contamination of the bare substrate on the total absorption of the coated
      substrate is studied for BK7 and fused-silica substrates. Then the mean value of
      the coated-substrate absorptance is shown to be strongly dependenton the type of
      substrate. Experimental results show that this effect is associated with a
      localization of the absorption at the near surface of the substrate and at the
      interfaces of the film.

PMID- 21102937
TI  - Optical and mechanical characterization of evaporated SiO(2) layers. Long-term
      evolution.
AB  - Numerous characterizations were performed on 120-nm thick evaporated SiO(2)
      layers in order to understand how their features change as a function of
      deposition conditions and time. Density decreases with increasing deposition
      pressure. It governs all the layer properties (refractive index, hardness, and
      stress). In situ stress measurements show that stress can be divided into
      intrinsic and water-induced components, respectively linked to local density
      (outside the pores) and porosity. Intrinsic stress increase with decreasing
      pressure is explained by a diminution of the Si-O-Si bond angle (IR
      measurements). Long-term evolution is characterized by stress relaxation related
      to Si-O-Si strained bond hydrolysis.

PMID- 21102938
TI  - Microstructural, optical, and mechanical properties of reactive electron-beam
      coevaporated TiO(2)-MgF(2) composite films.
AB  - The composition-dependent structural, microstructural, optical, and mechanical
      properties of TiO(2)-MgF(2) composite films prepared by reactive electron-beam
      coevaporation at a substrate temperature of 280  degrees C are systematically
      investigated with an x-ray diffractometer, transmission electron microscope,
      spectrophotometer and varied angle of incidence spectroscopic ellipsometry, and
      microhardness tester, respectively. A comparison of the films prepared by
      reactive ion-assisted coevaporation shows that the films prepared by reactive
      electron-beam coevaporation have lower refractive indices and hardnesses.
      However, TiO(2)-MgF(2) composite films prepared by both techniques exhibit
      similar softening and hardening phenomena and similar microstructures.

PMID- 21102939
TI  - Effects of surface compression strengthening on properties of indium tin oxide
      films deposited on automobile glass.
AB  - Indium tin oxide (ITO) films were deposited onto automobile glass substrates with
      dc reactive sputtering and ion-assisted e-beam-gun evaporation processes. The ITO
      coated glass samples were then strengthened through a surface compression
      strengthening process that included heating the glass at 650  degrees C for 5 min
      and rapidly cooling the exterior of the hot glass with air jets. The
      deterioration of electrical and optical properties of the ITO films on automobile
      safety glass was found during the heating stage of the strengthening process.
      When a layer of SiO(2) barrier was added, the property deterioration could be
      significantly reduced. The most effective barrier thickness was found near 60 nm,
      which resulted in no appreciable property loss.

PMID- 21102940
TI  - Consequences of Ti-, Li-, and Er-ion implantations on the optical properties of
      single layers of Ta(2)O(5).
AB  - Tantalum pentoxide (Ta(2)O(5)) layers made by ion plating are implanted with a
      high fluence of keV Ti, Li, and Er ions. The resulting refractive-index profiles
      are given from the analysis of guided-wave propagation conditions. A comparison
      with spectrophotometric measurements is presented. All the implanted layers
      present low losses (extinction coefficient of some 10(-6)) after thermal
      annealing in air. Ti-implanted layers exhibit an increase in refractive index,
      whereas Li- and Er-implanted layers present a slight decrease in refractive
      index. Er-implanted layers present photoluminescent properties.

PMID- 21102941
TI  - Optical properties of hafnia and coevaporated hafnia:magnesium fluoride thin
      films.
AB  - Mixed films of HfO(2) and MgF(2) were prepared by the e-beam coevaporation of two
      source materials with or without the presence of ion assistance. Optical
      properties and hardness of mixed films were compared among various compositions
      that were achieved by controlling the deposition rate of MgF(2). Results obtained
      from pure materials confirmed the densification of HfO(2) and the increased
      absorption in MgF(2) with a higher discharge voltage. A refractive index of a
      composite film from 1.38 to 1.91 was achievable with various HfO(2):MgF(2)
      deposition rate ratios. A low-index composite material with improved hardness may
      be substituted for the soft MgF(2).

PMID- 21102942
TI  - Silicon dioxide and hafnium dioxide evaporation characteristics from a high
      frequency sweep e-beam system.
AB  - Reactive oxygen evaporation characteristics were determined as a function of the
      front-panel control parameters provided by a programmable, high-frequency sweep e
      beam system. An experimental design strategy used deposition rate, beam speed,
      pattern, azimuthal rotation speed, and dwell time as the variables. The optimal
      settings for obtaining a broad thickness distribution, efficient silicon dioxide
      boule consumption, and minimal hafnium dioxide defect density were generated. The
      experimental design analysis showed the compromises involved with evaporating
      these oxides.

PMID- 21102943
TI  - Realization and optimization of planar refracting microlenses by Ag-Na ion
      exchange techniques.
AB  - We report the fabrication of planar microlenses with numerical apertures (N.A.'s)
      of 0.2 by field-assisted Ag-Na ion exchange in glass. To measure the N.A. of
      microlenses, different definitions can be used. We discuss the issue of measuring
      the N.A. and suggest an additional definition based on diffraction-limited
      performance. According to a simple model, the N.A. of a spherical lens is limited
      by the maximum index difference. Owing to this model, the N.A. for Ag-Na ion
      exchange is limited to a value of ~0.1. From measurements of microlenses,
      fabricated by field-assisted ion exchange, we obtained N.A.'s as high as 0.2,
      providing for diffraction-limited performance within the whole aperture.

PMID- 21102944
TI  - Comparison of phase-unwrapping algorithms by using gradient of first failure.
AB  - The comparison of phase-unwrapping algorithms has been an enigma because there
      has been no quantitative means of comparison. Noting that unwrapping routines are
      sensitive to noise and the local gradient of the phase array as well as fringe
      modulation, we have linked unwrapping performance to the gradient of first
      failure of the algorithm. When the gradient of first failure is plotted versus
      the signal-to-noise ratio, this can be used as an indicator of which algorithm to
      use in a given situation without the need for user intervention during the
      measurement and calculation. This study introduces three algorithms developed for
      their trade-offs in speed versus pixel noise (pointwise) sensitivity. The
      algorithms developed have been applied to live, noisy measurement data and have
      been proven to be robust.

PMID- 21102945
TI  - Deformation measurement with object-induced dynamic phase shifting.
AB  - A simple, yet powerful, means of computing the phase of fringe patterns depicting
      dynamic phenomena is presented. It is shown that the basic principle of the phase
      shifting methods can be extended to the case of dynamic situations. The crux is
      to recognize that the phenomenon under examination can itself provide the
      necessary incremental phase shifts. This new method possesses a very wide range
      of applications in the field of deformation measurement.

PMID- 21102946
TI  - Bandwidth limitations and dispersion in optical stellar interferometry.
AB  - The fringe visibility measured by a stellar interferometer may be degraded if the
      interferometer uses an air delay line without compensating for longitudinal
      dispersion. Whereas in such circumstances simultaneous observations across the
      visible spectrum are shown to be impracticable at baselines as short as 10 m, it
      is shown possible to detect 95% of the visibility amplitude if the measurements
      are made sequentially at different wavelengths and the fractional bandwidth
      Deltalambda/lambda at 950 nm is restricted to less than 10% when the baseline is
      10 m, 6% at 30 m, and 3% at 100 m.

PMID- 21102947
TI  - Radiometric calibration of the telescope and ultraviolet spectrometer SUMER on
      SOHO.
AB  - The prelaunch spectral-sensitivity calibration of the solar spectrometer SUMER
      (Solar Ultraviolet Measurements of Emitted Radiation) is described. SUMER is part
      of the payload of the Solar and Heliospheric Observatory (SOHO), which begins its
      scientific mission in 1996. The instrument consists of a telescope and a
      spectrometer capable of taking spatially and spectrally highly resolved images of
      the Sun in a spectral range from 50 to 161 nm. The pointing capabilities, the
      dynamic range, and the sensitivity of the instrument allow measurements both on
      the solar disk and above the limb as great as two solar radii. To determine
      plasma temperatures and densities in the solar atmosphere, the instrument needs
      an absolute spectral-sensitivity calibration. Here we describe the prelaunch
      calibration of the full instrument, which utilizes a radiometric transfer
      standard source. The transfer standard was based on a high-current hollow-cathode
      discharge source. It had been calibrated in the laboratory for vacuum UV
      radiometry of the Physikalisch-Technische Bundesanstalt by use of the calculable
      spectral photon flux of the Berlin electron storage ring for synchrotron
      radiation (BESSY)-a primary radiometric source standard.

PMID- 21102948
TI  - Survey of Ti-, B-, and Y-based soft x-ray-extreme ultraviolet multilayer mirrors
      for the 2- to 12-nm wavelength region.
AB  - We have performed an experimental investigation of Ti-, B(4)C-, B-, and Y-based
      multilayer mirrors for the soft x-ray?extreme ultraviolet (XUV) wavelength region
      between 2.0 and 12.0 nm. Eleven different material pairs were studied: Ti/Ni,
      Ti/Co, Ti/Cu, Ti/W, B(4)C/Pd, B/Mo, Y/Pd, Y/Ag, Y/Mo, Y/Nb, and Y/C. The
      multilayers were sputter deposited and were characterized with a number of
      techniques, including low-angle x-ray diffraction and normal incidence XUV
      reflectometry. Among the Ti-based multilayers the best results were obtained with
      Ti/W, with peak reflectances up to 5.2% at 2.79 nm at 61 degrees  from normal
      incidence. The B(4)C/Pd and B/Mo multilayer mirrors had near-normal incidence (5
      degrees ) peak reflectances of 11.5% at 8.46 nm and 9.4% at 6.67 nm,
      respectively, whereas a Y/Mo multilayer mirror had a maximum peak reflectance of
      25.6% at 11.30 nm at the same angle. The factors limiting the peak reflectance of
      these different multilayer mirrors are discussed.

PMID- 21102949
TI  - Fourier transform technique with refinement in the frequency domain for the
      synthesis of optical thin films.
AB  - An optical thin-film synthesis technique combining a Fourier transform approach
      with the refinement of design parameters in the Fourier space is proposed. The
      theory and numerical examples are described.

PMID- 21102950
TI  - Special configuration of a very large Schmidt telescope for extensive
      astronomical spectroscopic observation.
AB  - A special reflecting Schmidt telescope is used to observe celestial objects. The
      telescope has an aperture of 4m, f ratio of 5, and a 5 degrees  field of view.
      Its optical axis is fixed and tilted 25 degrees  to the horizontal that runs from
      south to north. The celestial objects were observed for 1.5 h as they passed
      through the meridian. The shape of the reflecting Schmidt plate has to be changed
      with each different declination delta and in the tracking process. This is
      achieved with active optics. The sky area to be observed is -10 degrees  <= delta
      <= +90 degrees . There are plans to place ~4000 optical fibers on the telescope
      focal surface that will lead to a dozen spectrographs.

PMID- 21102951
TI  - Distributed measurement of the complex modulation of a photoinduced Bragg grating
      in an optical fiber.
AB  - A method of measuring the complex modulation of a Bragg grating is derived from a
      one-dimensional model of light propagating in an optical fiber. Interference
      fringes between the Bragg grating and a reference air-gap reflector are measured,
      and a Fourier transform of the interference fringes generated as a laser is swept
      through the wavelength is used to compute the complex modulation function of the
      Bragg grating over a restricted domain. Supporting data, taken by temperature
      tuning a distributed feedback diode laser, are shown.

PMID- 21102952
TI  - Fiber-optic transmission of stretched pulses from a Q-switched ruby laser.
AB  - Fiber-optic transmission of Q-switched ruby laser pulses is limited by fiber
      damage owing to the high laser-beam intensities. Pulse stretching with a
      semiconductor-based control circuit for the Pockels cell of the ruby laser to
      reduce the peak intensities is described. Pulses with durations from 200 ns to 1
      MUs and a coherence length of ~3 m were generated. These pulses were coupled into
      multimode optical fibers to investigate the transmission characteristics and the
      limits of transmittable pulse energies. Stretched pulses can be transmitted in
      quartz fibers with a 600-MUm core diameter to pulse energies of 300 mJ, which is
      an increase by a factor of 4 compared with standard Q-switched pulses. It is
      expected that beam guiding of ruby laser pulses by fiber optics will
      significantly facilitate the use of holographic interferometry in technical
      applications such as vibration analysis.

PMID- 21102953
TI  - Asymmetric line shapes of the instrumental function found in two-etalon systems
      with a finite field of view.
AB  - The instrumental functions of the two-etalon system with a finite field of view
      have been examined in cases in which both etalons are inclined against the
      optical axis. The average transmittances of the rays in the finite field of view
      are obtained by numerical integration. It is shown that the line shape of the
      instrumental function becomes asymmetric, varying not only with the zenith angles
      of the symmetry axes of the two etalons but also with their azimuth angles.
      Experimental measurements of line shapes with the He-Ne laser show the asymmetric
      feature predicted by the calculation. The simulation calculations for the two
      pass etalon system are also carried out and show a drastic discrepancy in
      transmittances between azimuth angle differences of 0 degrees  and 180 degrees .

PMID- 21102954
TI  - Autocorrelation measurements of bursts of picosecond pulses.
AB  - In a master oscillator power amplifier system a powerful train of pulses can be
      generated. A simple method is described to measure the duration of these pulses.
      The measurements have been performed both at the fundamental frequency (1053 nm)
      and at the second harmonic (527 nm). In accordance with theoretical expectations
      we have observed a narrowing of the pulse owing to frequency doubling.

PMID- 21102955
TI  - Measurement of cylindrical particles with phase Doppler anemometry.
AB  - Light scattering from cylindrical particles has been described with geometric
      optics. The feasibility of determining the particle diameter with a planar phase
      Doppler anemometer has been examined by simulations and experiments. In
      particular, the influence of particle orientation on measurability and
      measurement accuracy has been investigated. Some recommendations for realizing a
      practical-measurement instrument have been presented.

PMID- 21102956
TI  - Surface-bonded and embedded optical fibers as ultrasonic sensors.
AB  - The effectiveness of surface-bonded and embedded optical fibers for the detection
      of ultrasonic Lamb waves in 2-3-mm-thick steel, carbon-fiber-reinforced plastic
      (CFRP) and glass-reinforced plastic (GRP) plates are compared. A novel
      integrating ultrasonic sensor was achieved using the signal arm of an actively
      stabilized 633-nm homodyne Mach-Zehnder fiber interferometer which was either
      bonded directly to the plate surface or spliced to single-mode fibers embedded
      within a composite plate during manufacture. An embedded fiber is shown to be
      about 20 times more sensitive to Lamb wave motions than a surface-bonded fiber.
      However, the latter may be more practical.

PMID- 21102957
TI  - Impact and vibration detection in composite materials by using intermodal
      interference in multimode optical fibers.
AB  - An optical fiber sensor based on the intermodal interference principle is
      integrated in a composite material to detect impacts and vibrations. Six fibers
      are integrated at the top of a carbon/epoxy composite panel so as to form a grid
      into the structure. Spectral and temporal responses to impacts and acoustic
      vibrations of the sensor are compared with a piezoelectric accelerometer. The
      tests proved the facility of integration and the high sensitivity of the device.
      The location of impacts is performed with this arrangement by measuring the
      arrival times of the front waves to the fibers.

PMID- 21102958
TI  - Fiber Bragg grating cryogenic temperature sensors.
AB  - Temperature sensing to as low as 80 K was demonstrated with 1.55-MUm fiber Bragg
      gratings. The gratings were bonded on substrates to increase sensitivity, and a
      shift of the reflection wavelength was measured. The temperature sensitivity was
      0.02 nm/K at 100 K when an aluminum substrate was used and 0.04 nm/K at 100 K
      when a poly(methyl methacrylate) substrate was used. These values are smaller
      than those at room temperature because of the nonlinearity of both the thermal
      expansion and the thermo-optic effect. Extension to the liquid helium temperature
      is also discussed.

PMID- 21102959
TI  - Optical-fiber sensor for simultaneous measurement of pressure and temperature:
      analysis of cross sensitivity.
AB  - The use of a highly elliptical core two-mode fiber for simultaneous measurement
      of pressure (radial pressure or hydrostatic pressure) and temperature is
      presented. The sources of errors are discussed. Expressions are developed to
      calculate the cross sensitivities. From the numerical examples, some useful
      conclusions are given.

PMID- 21102960
TI  - Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue
      diagnosis.
AB  - We have designed, fabricated, and tested a compact, transportable, excitation
      emission spectrofluorimeter with optical-fiber light delivery and collection for
      use in rapid analysis of tissues in a clinical setting. This system provides up
      to eleven different excitation wavelengths, permitting collection of all the
      corresponding emission spectra in approximately 600 ms. It uses a N(2) laser that
      pumps a sequence of dyes placed in cuvettes on a rotating wheel. A white-light
      excitation source permits acquisition of the tissue's diffuse reflectance
      spectrum on each cycle. Return fluorescence and reflected light are dispersed by
      a small spectrograph and detected by a photodiode-array detector. The system can
      collect a single-shot spectrum from biological tissue with a signal-to-noise
      ratio in excess of 50:1.

PMID- 21102961
TI  - Imaging acousto-optic tunable filter with 0.35-micrometer spatial resolution.
AB  - Image blur in acousto-optic tunable filters (AOTF's) has been a persistent
      problem. Here we describe the connection between transducer structure and image
      blur and experimentally measure it by using a 5-cm 12 degrees -cut TeO(2) crystal
      of our design. With these quantitative results, we develop an image-processing
      method that minimizes AOTF-related image degradation. The combination of long
      crystal design and image processing results in substantially improved image
      contrast and spatial resolution relative to conventional AOTF imaging devices. We
      present high-magnification images of fluorescent actin fibers in cells in which
      we obtain a resolution of approximately 0.35 MUm, representing the first
      successful use of an AOTF for ultra-high-resolution microscopy. Further
      improvements are also predicted.

PMID- 21102962
TI  - Phantom radiculitis effectively treated by fluoroscopically guided transforaminal
      epidural steroid injections.
AB  - Lower back and extremity pain in the amputee patient can be challenging to
      classify and treat. Radicular compression in a patient with lower limb amputation
      may present as or be superimposed upon phantom limb pain, creating diagnostic
      difficulties. Both patients and physicians classically find it difficult to
      discern phantom sensation from phantom limb pain and stump pain; radicular
      compression is often not considered. Many studies have shown back pain to be a
      significant cause of pain in lower limb amputees, but sciatica has been rarely
      reported in amputees. We present a case of L4/5 radiculitis in an above-knee
      amputee presenting as phantom radiculitis. Our patient is a 67 year old gentleman
      with new onset 10/10 pain in a phantom extremity superimposed upon a 40 year
      history of previously stable phantom limb pain. MRI showed a central disc
      herniation at L4/5 with compression of the traversing left L4 nerve root. Two
      fluoroscopically guided left transforaminal epidural steroid injections at the
      level of the L4 and L5 spinal nerve roots totally alleviated his new onset pain.
      At one year post injection, his phantom radiculitis pain was completely gone,
      though his underlying phantom limb pain remained. Lumbar radiculitis in lower
      extremity amputee patients may be difficult to differentiate from baseline
      phantom limb pain. When conservative techniques fail, fluoroscopically guided
      spinal nerve injection may be valuable in determining the etiology of lower
      extremity pain. Our experience supports the notion that epidural steroid
      injections can effectively treat phantom lumbar radiculitis in lower extremity
      amputees.

PMID- 21102963
TI  - Management of pain of post lumbar surgery syndrome: one-year results of a
      randomized, double-blind, active controlled trial of fluoroscopic caudal epidural
      injections.
AB  - BACKGROUND: Post lumbar surgery syndrome represents a cluster of nomenclature and
      syndromes following spine surgery wherein the expectations of the patient and
      spine surgeon are not met, with persistent pain following lumbar surgery.
      Multiple causes have been speculated to cause pain after lumbar surgery. Epidural
      steroid injections are most commonly used in managing post surgical pain in the
      lumbar spine. However, there is a paucity of evidence of epidural injections in
      managing chronic low back pain with or without lower extremity pain in post
      surgery syndrome. STUDY DESIGN: A randomized, double-blind, active controlled
      trial. SETTING: An interventional pain management practice, a specialty referral
      center, a private practice setting in the United States. OBJECTIVES: To evaluate
      the effectiveness of caudal epidural injections in patients with chronic low back
      and lower extremity pain after surgical intervention with post lumbar surgery
      syndrome. METHODS: One-hundred forty patients were randomly assigned to one of 2
      groups; Group I patients received caudal epidural injections with local
      anesthetic (lidocaine 0.5%), whereas Group II patients received caudal epidural
      injections with 0.5% lidocaine 9 mL mixed with 1 mL of 6 mg non-particulate
      Celestone. Randomization was performed by computer-generated random allocation
      sequence by simple randomization. OUTCOMES ASSESSMENT: Multiple outcome measures
      were utilized which included the Numeric Rating Scale (NRS), the Oswestry
      Disability Index 2.0 (ODI), employment status, and opioid intake with assessment
      at 3 months, 6 months, and 12 months post-treatment. Significant pain relief and
      disability reduction were described as 50% or more reduction in scores from
      baseline. RESULTS: Combined pain relief (>/=50%) and disability reduction was
      recorded in 53% of the patients in the local anesthetic group, and 59% of
      patients in the local anesthetic and steroid group with no significant
      differences noted with or without steroid over a period of one-year. However, the
      data from the successful group showed improvement in 70% of patients in Group I
      and 75% of patients in Group II. The average procedures per year were 4 with an
      average total relief per year of 38.1 +/- 14.5 weeks in Group I and 38.4 +/- 13.2
      weeks in Group II over a period of 52 weeks in the successful group. LIMITATIONS:
      The results of this study are limited by the lack of a placebo group and one-year
      outcomes. CONCLUSION: Caudal epidural injections in chronic function-limiting low
      back pain in post surgery syndrome without facet joint pain may be effective in a
      significant proportion of patients with improvement in functional status and
      significant pain relief. CLINICAL TRIAL: NCT00370799.

PMID- 21102964
TI  - Trial spinal cord stimulator reimplantation following lead breakage after third
      birth.
AB  - BACKGROUND: Many studies have reported lead migration and breakage as
      complications of epidural spinal cord stimulation. In cases where rapid changes
      in physique such as those caused by pregnancy are expected, it is unclear whether
      extra consideration regarding possible adjustments and care to avoid
      complications such as lead breakage are required. OBJECTIVE: This article
      presents a case in which spinal cord stimulation was used to manage these
      complications in a woman during the perinatal period. DESIGN: Case report.
      SETTING: Pain management clinic. METHODS: The patient was a 36-year-old female,
      approximate weight of 100 pounds, and 5-foot 1 inch in height, whose chief
      complaint was lower back and bilateral leg pain. The pain could not be alleviated
      by conservative therapies such as nerve blockade, oral medications with non
      steroidal anti-inflammatory drugs, antidepressants, anticonvulsants or physical
      therapy. A spinal cord stimulator was implanted at another facility, which
      relieved the pain. The patient subsequently had 2 vaginal births without any
      problems relating to the stimulation sites, and both infants were healthy. She
      experienced lead breakage after the third vaginal birth that led to the
      subsequent reimplantation procedure. RESULTS: The patient had 2 subsequent
      vaginal births following the initial implantation with no problems related to the
      stimulation sites, and both infants were healthy. At age 34, following her third
      vaginal birth, the stimulator became ineffective and was removed. The withdrawn
      lead wire was found to be broken in 2 places. LIMITATIONS: A case report.
      CONCLUSION: Pregnancy following implantation of a spinal cord stimulator might
      result in lead breakage as abdominal girth increases. The present case
      exemplifies how pregnancy following implantation of a spinal cord stimulator
      might cause lead breakage as abdominal girth increases. Extra care is required to
      prevent lead breakage when anchors are fixed.

PMID- 21102965
TI  - The benefit of therapeutic medial branch blocks after cervical operations.
AB  - BACKGROUND: Persistent neck pain is a common problem after surgery of the
      cervical spine. No therapy recommendation exists for these patients. OBJECTIVE:
      The objective of this study was to determine if a therapeutic medial branch block
      is a rational treatment for patients with postoperative neck pain after cervical
      spine operations. STUDY DESIGN: Retrospective practice audit. SETTING: Review of
      charts of all patients who underwent cervical spine operations for degenerative
      reasons during a time period of 3 years. METHODS: Patients with persistent
      postsurgical pain were treated with therapeutic medial branch blocks (local
      anesthetic and steroid). A positive treatment response was defined if at least
      80% reduction of pain could be achieved or if the patient was sufficiently
      satisfied with the relief. All patients with a minimum follow up time of 6 months
      were included. RESULTS: Of the 312 operations performed, 128 were artificial disc
      operations, 125 were stand alone cages, and 59 were fusions with cage and plate.
      Persistent neck pain occurred in 33.3% of the patients. There was no difference
      between the patients with neck pain and the whole group of patients. More than
      half of the patients with neck pain--52.9%--were treated successfully with
      therapeutic medial branch blocks. Since no further treatment was necessary, the
      initial treatment was considered successful. Nearly a third--32.2%--of the
      patients were initially treated successfully, but their pain recurred and further
      diagnostics and treatments were necessary. In this group of patients,
      significantly more with double level operations were found (P = 0.003). Patients
      not responding to the medial branch block were 14.9%. LIMITATIONS: This audit is
      retrospective and observational, and therefore does not represent a high level of
      evidence. However, to our knowledge, since this information has not been
      previously reported and no recommendation for the treatment of post-operative
      zygapophysial joint pain exists, it appears to be the best available research
      upon which to recommend treatment and to plan higher quality studies. CONCLUSION:
      For persistent postsurgical neck pain only limited therapy recommendations exist.
      This study suggests treating these patients in a first instance with therapeutic
      medial branch blocks. The success rate is 52.9 %.

PMID- 21102966
TI  - Comparative effectiveness of a one-year follow-up of thoracic medial branch
      blocks in management of chronic thoracic pain: a randomized, double-blind active
      controlled trial.
AB  - BACKGROUND: Thoracic facet joints have been implicated as the source of chronic
      pain in the mid back or upper back in 34% to 42% of patients when the modified
      criteria of the International Association for the Study of Pain (IASP) is
      utilized. Various therapeutic techniques utilized in managing chronic thoracic
      pain of facet joint origin include intraarticular injections, medial branch
      blocks, and radiofrequency neurotomy of thoracic medial branch nerves. STUDY
      DESIGN: A randomized, double-blind, active controlled trial. SETTING: A private
      practice, interventional pain management setting, and a specialty referral center
      setting in the United States. OBJECTIVE: To determine the clinical effectiveness
      of therapeutic local anesthetic medial branch blocks with or without steroid in
      managing chronic function-limiting mid back or upper back pain of facet joint
      origin. METHODS: The study was performed in an interventional pain management
      private practice, a tertiary referral center, in the United States. A total of
      100 participants were included, with 50 participants in each of the local
      anesthetic and steroid groups. All of the participants met the diagnostic
      criteria of thoracic facet joint pain by means of comparative, controlled
      diagnostic blocks and the inclusion criteria. Group I participants received
      thoracic medial branch blocks with bupivacaine, whereas Group II participants
      received thoracic medial branch blocks with bupivacaine and non-particulate
      betamethasone. OUTCOMES ASSESSMENT: Outcomes measures included numeric rating
      scores (NRS), Oswestry Disability Index (ODI), opioid intake, and return to work
      status at baseline, 3 months, 6 months, and 12 months. Significant pain relief
      was defined as >/= 50% pain relief and/or a positive change in ODI scores.
      RESULTS: In Group I and Group II 90% of participants showed significant pain
      relief and functional improvement at 12 months. The majority of the participants
      experienced significant pain relief of 47.2 +/- 10.1 weeks in Group I and 46.3 +/
      8.4 weeks in Group II, requiring approximately 3.5 treatments per year with an
      average relief of 15.8 +/- 10.5 in Group I and 13.6 +/- 3.6 weeks in Group II per
      episode of treatment. LIMITATIONS: Study limitations include the lack of a
      placebo group. CONCLUSIONS: Therapeutic thoracic medial branch blocks, with or
      without steroid, may provide a management option for chronic function-limiting
      mid back or upper back pain of facet joint origin. CLINICAL TRIAL: NCT00355706.

PMID- 21102968
TI  - Retrospective review of patient self-reported improvement and post-procedure
      findings for mild (minimally invasive lumbar decompression).
AB  - BACKGROUND: Lumbar spinal stenosis and neurogenic claudication functionally
      impact thousands of patients per year. Those who fail conservative therapies and
      are not surgical candidates due to co-morbid conditions have few interventional
      options available. The recently described mild(r) procedure (Minimally Invasive
      Lumbar Decompression) is a candidate to fill this void. While 2 studies have
      reported no major adverse events with this procedure, the typical post-procedure
      patient course has not been previously described. OBJECTIVE: To examine the minor
      adverse events and periprocedural course associated with mild. Additionally, to
      evaluate the efficacy of the procedure with regard to pain relief and functional
      status. DESIGN: Retrospective evaluation. METHODS: Forty-two consecutive patients
      meeting magnetic resonance imaging (MRI) criteria for mild underwent the
      procedure performed by 2 interventional pain management physicians working at the
      same center. The pre and post procedure visual analog scale (VAS) as well as
      markers of global function were recorded. Major and minor adverse events were
      tracked and patient outcomes reported. RESULTS: There were no major adverse
      events reported. Of the minor adverse events, soreness lasting 3.8 days was most
      frequently reported. No patients required overnight observation and only 5
      required postoperative opioid analgesics. Patients self-reported improvement in
      function as assessed by ability to stand and ambulate for greater than 15
      minutes, whereas prior to the procedure 98% reported significant limitations in
      these markers of global functioning. Visual analog pain scores were significantly
      decreased by 40% from baseline. Eighty-six percent of the patients reported that
      they would recommend the mild procedure to others. CONCLUSION: The mild procedure
      appears to be a safe and likely effective option for treatment of neruogenic
      claudication in patients who have failed conservative therapy and have ligamentum
      flavum hypertrophy as the primary distinguishing component of the stenosis.

PMID- 21102967
TI  - Osteoid osteoma and osteoblastoma of the cervical spine: the cause of unusual
      persistent neck pain.
AB  - BACKGROUND: The most important symptom in patients with osteoid osteoma and
      osteoblastoma is a resistant localized neck pain and stiffness in the spine.
      OBJECTIVE: To evaluate and analyze 6 cases of osteoid osteoma and osteoblastoma
      of the cervical spine that were surgically treated over a 7-year period and to
      emphasize the unusual persistent neck pain associated with osteoid osteoma and
      osteoblastoma of the cervical spine. STUDY DESIGN: Retrospective study. METHODS:
      Six patients, 3 male and 3 female, with a mean age of 21 years (range 16-31)
      diagnosed with osteoid osteoma or osteoblastoma during 2003 to 2009 were analyzed
      retrospectively. The preoperative neurological and clinical symptoms, neck pain
      duration, preoperative deformity, location of lesion, radiological findings,
      surgical technique and clinical follow-up outcomes of each patient were
      evaluated. RESULTS: The average follow-up duration was 40.5 months (range, 19 to
      83 months). Three patients had osteoid osteoma (2 female and one male), and 3
      patients had osteoblastoma (one female and 2 male). Two male patients had
      recurrent osteoblastoma. The locations of the lesions were as follows: C7 (2
      patients), C3 (one patient), C2 (one patient), C3-C4 (one patient) and C5-C6 (one
      patient). The most common symptom was local neck pain in the region of the tumor.
      Among all patients, only one patient, who had osteoblastoma, had neurological
      deficits (right C5-C6 root symptoms). The other patients had no neurological
      deficits. All patients were treated with surgical resection using microsurgery.
      Two patients underwent only tumor resection, one patient underwent tumor
      resection and fusion, and the other 3 patients underwent tumor resection, fusion
      and spinal instrumentation. No perioperative complications developed in any of
      our patients. There was no tumor recurrence during the follow-up period.
      LIMITATIONS: A retrospective study with 6 analyses of cases. CONCLUSION: Surgical
      treatment of osteoid osteoma and osteoblastoma of the spine has been
      standardized. The most common symptom of osteoid osteoma and osteoblastoma of the
      cervical spine is local persistent neck pain in the region of the tumor. This
      symptom can be significant in the diagnosis of these tumors.

PMID- 21102969
TI  - Reduced cognitive and psychomotor impairment with extended-release oxymorphone
      versus controlled-release oxycodone.
AB  - BACKGROUND: Opioids provide effective pain control, yet have risks including
      adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and
      cognitive/psychomotor effects. OBJECTIVE: To compare cognitive and psychomotor
      effects of oxymorphone extended release (OM-ER) versus oxycodone controlled
      release (OC-CR). STUDY DESIGN: Randomized, double-blind, 5-way crossover SETTING:
      Single inpatient research unit METHODS: Nondependent recreational opioid users
      were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg),
      and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided
      attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g.,
      percentage over road], target accuracy [e.g., target hits], reaction time [hit
      latency]). Visual analog scales measured alertness/drowsiness,
      agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects
      were measured using the Addiction Research Center Inventory Pentobarbital
      Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid
      Diethylamide (LSD) scales, respectively. Comparisons were made between
      equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg),
      within active drug doses, and between active drugs and placebo using least
      squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect
      using linear mixed model analysis of covariance. RESULTS: Thirty-five
      participants received all 5 treatments. Peak cognitive and psychomotor impairment
      (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction
      time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4],
      P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms
      [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs
      604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking
      accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4],
      P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target
      hits percentage, lower if impaired; 81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1]
      vs 66.1 [3.1], P<0.001). Several other DA measures showed that OC-CR, especially
      60 mg, produced more psychomotor impairment than equianalgesic OM-ER. Compared to
      OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30
      mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both
      equianalgesic dose groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30
      mg; P=0.001 for OM-ER 30 mg vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for
      both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both
      equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg
      vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more
      commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting,
      dizziness). LIMITATIONS: Participants were young, healthy volunteer nondependent
      recreational drug users, and only single doses were evaluated. The effects of
      tampering or higher doses were not assessed. CONCLUSION: Single oral intact low
      and high doses of OM-ER produced less cognitive and psychomotor impairment plus
      less sedation than equianalgesic OC-CR in this exploratory study.
      ClinicalTrials.gov registration NCT00955110.

PMID- 21102971
TI  - Ketamine-induced urologic insult (KIUI).

PMID- 21102972
TI  - Injection treatment and back pain associated with degenerative lumbar spinal
      stenosis in older adults.
AB  - BACKGROUND: Lower back pain is one of the most common health-related complaints
      in the adult population. Thirty percent of Americans 65 years and older reported
      symptoms of lower back pain in 2004 (NCHS, 2006). Injection treatment is a
      commonly used non-surgical procedure to alleviate lower back pain in older
      adults. However, the effectiveness of injection treatment, particularly in older
      adults, has not been well documented. OBJECTIVE: This study quantified the
      effectiveness of injection treatment on pain relief among adults 60 years and
      over who were diagnosed with degenerative lumbar spinal stenosis, a common cause
      of lower back pain in older adults. The variations of the effectiveness were
      examined by selected patient attributes. STUDY DESIGN: Prospective, non
      randomized, observational human study. SETTING: Single institution spine clinic.
      METHODS: Patients scheduled for lumbar injection treatment between January 1 and
      July 1, 2008 were prospectively selected from the study spine clinic. Selection
      criteria included patients age 60 and over, diagnosed with degenerative lumbar
      spinal stenosis and no previous lumbar injection within 6 months or lumbar
      surgery within 2 years. The pain sub-score of the SF-36 questionnaire was used to
      measure pain at baseline and at one and 3 months post injection. Variations in
      longitudinal changes in pain scores by patient characteristics were analyzed in
      both unadjusted (univariate) analyses using one-way analysis of variance (ANOVA),
      and adjusted (multiple regression) analyses using linear mixed effects models.
      LIMITATIONS: This study is limited by its sample size and observational design.
      RESULTS: Of 62 patients receiving epidural steroid injections, the mean Pain
      score at baseline was 27.4 (SD =13.6), 41.7 (SD = 22.0) at one month and 35.8 (SD
      = 19.0) at 3 months. Mean Pain scores improved significantly from baseline to one
      month (14.1 points), and from baseline to 3 months (8.3 points). Post injection
      changes in pain scores varied by body mass index (BMI) and baseline emotional
      health. Based on a linear mixed effects model analysis, higher baseline emotional
      health, as measured by the SF-36 Mental Component Score (MCS >/= 50), was
      associated with greater reduction in pain over 3 months when compared to lower
      emotional health (MCS), was associated with greater reduction in pain over 3
      months when compared to lower emotional health (MCS <50). In patients with higher
      emotional health, pain scores improved by 14.1 (P < .05: 95% CI 6.9, 21.3).
      Patients who were obese also showed significant improvement in pain scores over 3
      months compared to non-obese patients. In obese patients, pain scores increased
      by 7.9 (P <.05; 95% CI:1.0, 14.8) points. CONCLUSION: Lower back pain in older
      adults with degenerative lumbar spinal stenosis might be clinically significantly
      alleviated after injection treatment. Pain relief varies by a patients personal
      and clinical characteristics. Healthier emotional status and obesity appears to
      be associated with more pain relief experienced over 3 months following
      injection.

PMID- 21102973
TI  - A preliminary report of a randomized double-blind, active controlled trial of
      fluoroscopic thoracic interlaminar epidural injections in managing chronic
      thoracic pain.
AB  - BACKGROUND: The proportion of patients suffering from thoracic pain secondary to
      thoracic disorders is relatively small compared to low back and neck pain.
      Furthermore, thoracic interventions are not performed as often as in cervical and
      lumbar regions. In addition, there is a paucity of literature regarding thoracic
      intervertebral discs and thoracic disc herniation as causative structures of
      thoracic pain. STUDY DESIGN: A randomized, double-blind, active controlled trial.
      SETTING: A private practice, interventional pain management and specialty
      referral center in the United States. OBJECTIVES: To evaluate the effectiveness
      of thoracic interlaminar epidural injections in providing effective pain relief
      in managing chronic mid and upper back pain secondary to disc herniation or
      radiculitis and discogenic pain with local anesthetic alone or with steroids.
      METHODS: Inclusion criteria consisted of patients who either had disc herniation
      or radiculitis, or patients with discogenic pain proven by controlled comparative
      local anesthetic blocks not to be caused by facet joint pain. Patients were
      assigned to one of 2 groups. One group received injections containing local
      anesthetic only; the other group, local anesthetic mixed with non-particulate
      betamethasone. Randomization was performed by computer-generated random
      allocations sequence by simple randomization. OUTCOMES ASSESSMENT: Participant
      outcomes were measured at baseline, 3, 6, and 12 months post-treatment with the
      Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment
      status, and opioid intake. Decrease of >/= 50% of NRS scores and Oswestry scores
      were considered significant. RESULTS: A total of 40 participants are included in
      this preliminary report with 20 participants in each group. Significant pain
      relief (>/= 50%) and reduction (by at least 50%) in ODI from baseline was seen at
      12 months in 80% of patients in Group I and 85% in Group II. LIMITATIONS: This is
      a preliminary report and there was no placebo group. Overall, 80% of participants
      in Group I (who received injections without steroids) and 85% in Group II (who
      received injections with steroids) with thoracic pain secondary to disc
      herniation or radiculitis and discogenic pain might benefit from thoracic
      interlaminar epidural injections. CLINICAL TRIAL: NCT01071369.

PMID- 21102974
TI  - Ketamine infusion successful in some patients.

PMID- 21102976
TI  - Transforaminal block and paraplegia: a two-edged lurking reef.

PMID- 21102978
TI  - Paraparesis following spinal cord stimulator trial, implantation and revision.

PMID- 21102979
TI  - Vaccination for H1N1 in influenza.

PMID- 21102980
TI  - Duty to warn?-the ethics of disclosing information about possible risks
      associated with H1N1 vaccination.

PMID- 21102981
TI  - Post-H1N1 narcolepsy-cataplexy.

PMID- 21102982
TI  - Sleep. Eat. Perform?

PMID- 21102983
TI  - Social experience and personality affect resilience to sleep deprivation.

PMID- 21102984
TI  - Treatment of Obstructive Sleep Apnea may be an Important Adjunct to Therapy of
      Posttraumatic Stress Disorder not to be Overlooked.

PMID- 21102985
TI  - Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem
      cells and activates developmental transcriptional programs in mice.
AB  - BACKGROUND: obstructive sleep apnea is a prevalent disorder associated with
      cognitive dysfunction and cardiovascular and metabolic morbidity and is
      characterized by recurrent episodes of hypoxia during sleep. Bone marrow-derived
      very small embryonic-like (VSEL) pluripotent stem cells represent a recruitable
      pool that may play an important role in organ repair after injury. We
      hypothesized that exposure to intermittent hypoxia (IH) can mobilize VSELs from
      the bone marrow (BM) to peripheral blood (PB) in mice and can activate distinct
      transcriptional programs. METHODS: adult mice were exposed to IH or normoxia for
      48 hours. VSELs were sorted from BM and PB using flow cytometry. Plasma levels of
      stem cell chemokines, stromal cell derived factor-1 (SDF-1), hepatocyte growth
      factor (HGF), and leukemia inhibitory factor (LIF) were measured. Transcriptional
      profiling of VSELs was performed, and differentially expressed genes were mapped
      to enriched functional categories and genetic networks. RESULTS: exposure to IH
      elicited migration of VSELs from BM to PB and elevations in plasma levels of
      chemokines. More than 1100 unique genes were differentially expressed in VSELs in
      response to IH. Gene Ontology and network analysis revealed the activation of
      organ-specific developmental programs among these genes. CONCLUSIONS: exposure to
      IH mobilizes VSELs from the BM to PB and activates distinct transcriptional
      programs in VSELs that are enriched in developmental pathways, including central
      nervous system development and angiogenesis. Thus, VSELs may serve as a reserve
      mobile pool of pluripotent stem cells that can be recruited into PB and may play
      an important role in promoting end-organ repair during IH.

PMID- 21102986
TI  - The association between sleep disordered breathing, academic grades, and
      cognitive and behavioral functioning among overweight subjects during middle to
      late childhood.
AB  - STUDY OBJECTIVES: (1) to determine the associations of sleep disordered breathing
      (SDB) with behavioral functioning, cognitive test scores, and school grades
      during middle- to late-childhood, an under-researched developmental period in the
      SDB literature, and (2) to clarify whether associations between SDB and school
      grades are mediated by deficits in cognitive or behavioral functioning. DESIGN:
      cross-sectional correlative study. SETTING: Office/hospital, plus reported
      functioning at home and at school. PARTICIPANTS: 163 overweight subjects aged 10
      16.9 years were divided into 4 groups based upon their obstructive apnea+hypopnea
      index (AHI) during overnight polysomnography and parent report of snoring:
      Moderate-Severe OSA (AHI > 5, n = 42), Mild OSA (AHI = 1-5, n = 58), Snorers (AHI
      < 1 + snoring, n = 26), and No SDB (AHI < 1 and nonsnoring, n = 37).
      MEASUREMENTS: inpatient overnight polysomnography, parent- and self-report of
      school grades and sleep, parent- and teacher-report of daytime behaviors, and
      office-based neuropsychological testing. RESULTS: The 4 groups significantly
      differed in academic grades and parent- and teacher-reported behaviors,
      particularly inattention and learning problems. These findings remained
      significant after adjusting for subject sex, race, socioeconomic status, and
      school night sleep duration. Associations with SDB were confined to reports of
      behavioral difficulties in real-world situations, and did not extend to office
      based neuropsychological tests. Findings from secondary analyses were consistent
      with, but could not definitively confirm, a causal model in which SDB affects
      school grades via its impact on behavioral functioning. CONCLUSIONS: SDB during
      middle- to late-childhood is related to important aspects of behavioral
      functioning, especially inattention and learning difficulties, that may result in
      significant functional impairment at school.

PMID- 21102987
TI  - Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a
      retrospective study of 51 children.
AB  - STUDY OBJECTIVE: to report on symptoms and therapies used in childhood narcolepsy
      cataplexy. DESIGN, PATIENTS, AND SETTING: retrospective series of 51 children who
      completed the Stanford Sleep Inventory. HLA-DQB1*0602 typing (all tested, and
      100% positive), polysomnography or Multiple Sleep Latency Test (76%), and
      cerebrospinal fluid hypocretin-1 measurements (26%, all with low levels) were
      also conducted. Prospective data on medication response was collected in 78%
      using a specially designed questionnaire. MEASUREMENTS AND RESULTS: patients were
      separated into children with onset of narcolepsy prior to (53%), around (29%),
      and after (18%) puberty. None of the children had secondary narcolepsy. Clinical
      features were similar across puberty groups, except for sleep paralysis, which
      increased in frequency with age. Common features included excessive weight gain
      (84% >= 4 kg within 6 months of onset of narcolepsy) and earlier puberty (when
      compared with family members), notably in subjects who gained the most weight.
      Streptococcus-positive throat infections were reported in 20% of cases within 6
      months of onset of narcolepsy. Polysomnographic features were similar across
      groups, but 3 prepubertal children did not meet Multiple Sleep Latency Test
      diagnostic criteria. Regarding treatment, the most used and continued medications
      were modafinil (84% continued), sodium oxybate (79%), and venlafaxine (68%).
      Drugs such as methylphenidate, tricyclic antidepressants, or selective serotonin
      reuptake inhibitors were often tried but rarely continued. Modafinil was reported
      to be effective for treating sleepiness, venlafaxine for cataplexy, and sodium
      oxybate for all symptoms, across all puberty groups. At the conclusion of the
      study, half of children with prepubertal onset of narcolepsy were treated "off
      label" with sodium oxybate alone or with the addition of one other compound. In
      older children, however, most patients needed more than 2 drugs. CONCLUSION: this
      study reports on the clinical features of childhood narcolepsy and documents the
      safe use of treatments commonly used in adults in young children.

PMID- 21102988
TI  - Coping with sleep deprivation: shifts in regional brain activity and learning
      strategy.
AB  - STUDY OBJECTIVES: dissociable cognitive strategies are used for place navigation.
      Spatial strategies rely on the hippocampus, an area important for flexible
      integration of novel information. Response strategies are more rigid and involve
      the dorsal striatum. These memory systems can compensate for each other in case
      of temporal or permanent damage. Sleep deprivation has adverse effects on
      hippocampal function. However, whether the striatal memory system can compensate
      for sleep-deprivation-induced hippocampal impairments is unknown. DESIGN: with a
      symmetrical maze paradigm for mice, we examined the effect of sleep deprivation
      on learning the location of a food reward (training) and on learning that a
      previously nonrewarded arm was now rewarded (reversal training). MEASUREMENTS AND
      RESULTS: five hours of sleep deprivation after each daily training session did
      not affect performance during training. However, in contrast with controls, sleep
      deprived mice avoided a hippocampus-dependent spatial strategy and preferentially
      used a striatum-dependent response strategy. In line with this, the training
      induced increase in phosphorylation of the transcription factor cAMP response
      element binding protein (CREB) shifted from hippocampus to dorsal striatum.
      Importantly, although sleep-deprived mice performed well during training,
      performance during reversal training was attenuated, most likely due to rigidity
      of the striatal system they used. CONCLUSIONS: together, these findings suggest
      that the brain compensates for negative effects of sleep deprivation on the
      hippocampal memory system by promoting the use of a striatal memory system.
      However, effects of sleep deprivation can still appear later on because the
      alternative learning mechanisms and brain regions involved may result in reduced
      flexibility under conditions requiring adaptation of previously formed memories.

PMID- 21102989
TI  - Socializing by Day May Affect Performance by Night: Vulnerability to Sleep
      Deprivation is Differentially Mediated by Social Exposure in Extraverts vs
      Introverts.
AB  - STUDY OBJECTIVES: to examine the effects of socially enriched versus socially
      impoverished environments on performance and alertness decline during sleep
      deprivation in extraverts versus introverts. DESIGN: participants (n = 29 men, n
      = 19 women) were assigned to socially enriched (n = 24; 13 introverts, 11
      extraverts) or socially impoverished (n = 24; 12 introverts, 12 extraverts)
      conditions (activities matched) for 12 hours (1000-2200) on Day 1 followed by 22
      hours of sleep deprivation (2200-2000; 36 h awake total), monitored by
      actigraphy. The median split of volunteers' Eysenck Extraversion scores was used
      for extravert/introvert categorization. The Psychomotor Vigilance Task (PVT),
      modified Maintenance of Wakefulness Test (MWT), and Stanford Sleepiness Scale
      (SSS) were administered every 2 hours throughout. PVT speed, transformed lapses,
      modified MWT sleep-onset latency, and SSS were analyzed using mixed-model
      analyses of variance, with covariates of age and total actigraphic activity
      during enrichment or impoverishment. SETTING: residential sleep/performance
      testing facility. PARTICIPANTS: forty-eight healthy adults (aged 18-39).
      INTERVENTIONS: Twelve hours of socially enriched or isolated environments in
      extraverts and introverts prior to sleep deprivation. RESULTS: Social experience
      interacted with personality type to affect alertness and vigilance. Social
      enrichment, as compared with social impoverishment, was associated with more PVT
      lapses at 04:00 overall. Similarly, following social enrichment, PVT speed was
      significantly slower among extraverts than among introverts during sleep
      deprivation, but no personality-group differences emerged following social
      impoverishment. MWT sleep latency and SSS subjective sleepiness did not show
      significant personality or social-condition effects during sleep deprivation.
      CONCLUSIONS: the effect of social exposure on vulnerability or resiliency to
      sleep deprivation was modulated by introversion and extraversion. Extraverts
      exposed to social environments were more vulnerable to subsequent sleep
      deprivation than were introverts.

PMID- 21102990
TI  - Parent and self-report of sleep-problems and daytime tiredness among adolescents
      with inflammatory bowel disease and their population-based controls.
AB  - STUDY OBJECTIVES: to evaluate the frequency of sleep problems and daytime
      tiredness among adolescents with inflammatory bowel disease (IBD) in comparison
      with their healthy peers. DESIGN: Parent and self-reports of sleep problems and
      daytime tiredness. SETTING: questionnaire-based postal survey. INTERVENTION: N/A.
      PARTICIPANTS: one hundred sixty Finnish adolescents with IBD; 236 adolescents
      matched for age, sex, and place of residence; and the parents of both groups.
      MEASUREMENTS AND RESULTS: Sleep Self-Report and sleep questions of the Child
      Behavior Check-List, and Youth Self-Report. The parents of adolescents with IBD
      reported in their index child more trouble sleeping (P < 0.01), more nightmares
      (P < 0.01), sleeping more than most children during the day/night (P < 0.001),
      and overtiredness (P < 0.001) than did the parents of control subjects. In
      contrast, adolescents with IBD themselves did not report more problems than their
      peers. However, in the group of patients with self-reported severe IBD symptoms,
      both the parents and the adolescents reported trouble sleeping and overtiredness
      more often (P values < 0.01) than in the group with mild symptoms or control
      subjects. Adolescents with severe IBD reported more often that their symptoms
      affected the quality of their sleep (P < 0.001) than did adolescents with mild
      disease. CONCLUSIONS: adolescents with severe IBD symptoms have disturbed sleep
      and are overtired more often than are adolescents with mild IBD symptoms or
      control subjects. Thus, in adolescents with severe IBD symptoms, evaluating sleep
      is important in characterizing the disease burden. Both parent and adolescent
      reports are needed for comprehensive assessment of sleep in the young.

PMID- 21102991
TI  - Positive airway pressure adherence in veterans with posttraumatic stress
      disorder.
AB  - STUDY OBJECTIVES: to determine the short-term positive airway pressure (PAP)
      adherence rates and to identify non-mask-related risk factors associated with 30
      day nonadherence to PAP in a population of veterans with obstructive sleep apnea
      (OSA) and posttraumatic stress disorder (PTSD). DESIGN: a retrospective study.
      SETTINGS: a Veterans Affairs hospital. PATIENTS: one hundred forty-eight PTSD
      veterans newly diagnosed with OSA and a control group of OSA without PTSD matched
      for age, gender, BMI, and severity of OSA. INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: at 30-day follow-up, adherence to PAP was significantly lower in the
      PTSD group compared to the control group (41% versus 70%, respectively; P <
      0.001). Veterans with adequate PAP adherence were more likely to experience
      sleepiness at baseline compared to nonadherent subjects (ESS 14.4 +/- 5.3 versus
      12.3 +/- 5.9, respectively; P = 0.04). Nightmares were more frequently reported
      in those who were PAP nonadherent (P = 0.002). Mask discomfort, claustrophobia,
      and air hunger were the reported reasons for PAP nonadherence in the PTSD group.
      CONCLUSION: PAP usage and adherence were lower in PTSD veterans with OSA than
      veterans without PTSD. Excessive sleepiness predicted PAP adherence while
      frequent nightmares were correlated with poor adherence to PAP therapy.

PMID- 21102992
TI  - Contribution of cancer symptoms, dysfunctional sleep related thoughts, and sleep
      inhibitory behaviors to the insomnia process in breast cancer survivors: a daily
      process analysis.
AB  - STUDY OBJECTIVES: using a comprehensive cognitive-behavioral model of insomnia
      and a daily process approach, this study was conducted to examine the
      contribution of cancer symptoms and dysfunctional sleep related thoughts and
      behaviors to the process of insomnia in breast cancer survivors. DESIGN: within
      group longitudinal research design. SETTING: an academic medical center.
      PARTICIPANTS: 41 women with breast cancer who had completed their primary cancer
      treatment and met Research Diagnostic Criteria for primary insomnia or insomnia
      comorbid with breast cancer. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: for 28
      days, participants completed morning diaries assessing sleep, nighttime pain and
      hot flashes, and dysfunctional sleep related thoughts and behaviors during the
      day and night, and evening diaries assessing daytime pain, fatigue, hot flashes,
      and mood. All diaries were collected using an automated telephone-based system.
      Results revealed that poorer sleep was related to nighttime pain and hot flashes
      in breast cancer patients. Time-lagged effects were also found. The current study
      identified higher levels of dysfunctional sleep related thoughts and sleep
      inhibitory behaviors during the day and night as antecedents of insomnia, and
      higher levels of pain, fatigue, and hot flashes and lower levels of positive mood
      and dysfunctional sleep related thoughts as consequences of insomnia in this
      population. CONCLUSIONS: the current study found support for a comprehensive
      cognitive-behavioral model of insomnia, which has several theoretical, practice,
      and research implications.

PMID- 21102993
TI  - Analysis of slow-wave activity and slow-wave oscillations prior to somnambulism.
AB  - STUDY OBJECTIVIES: several studies have investigated slow wave sleep EEG
      parameters, including slow-wave activity (SWA) in relation to somnambulism, but
      results have been both inconsistent and contradictory. The first goal of the
      present study was to conduct a quantitative analysis of sleepwalkers' sleep EEG
      by studying fluctuations in spectral power for delta (1-4 Hz) and slow delta (0.5
      1 Hz) before the onset of somnambulistic episodes. A secondary aim was to detect
      slow-wave oscillations to examine changes in their amplitude and density prior to
      behavioral episodes. PARTICIPANTS: twenty-two adult sleepwalkers were
      investigated polysomnographically following 25 h of sleep deprivation. RESULTS:
      analysis of patients' sleep EEG over the 200 sec prior to the episodes' onset
      revealed that the episodes were not preceded by a gradual increase in spectral
      power for either delta or slow delta over frontal, central, or parietal leads.
      However, time course comparisons revealed significant changes in the density of
      slow-wave oscillations as well as in very slow oscillations with significant
      increases occurring during the final 20 sec immediately preceding episode onset.
      CONCLUSIONS: the specificity of these sleep EEG parameters for the occurrence and
      diagnosis of NREM parasomnias remains to be determined.

PMID- 21102994
TI  - Eye movements and abducens motoneuron behavior after cholinergic activation of
      the nucleus reticularis pontis caudalis.
AB  - STUDY OBJECTIVES: the aim of this work was to characterize eye movements and
      abducens (ABD) motoneuron behavior after cholinergic activation of the nucleus
      reticularis pontis caudalis (NRPC). METHODS: six female adult cats were prepared
      for chronic recording of eye movements (using the scleral search-coil technique),
      electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves in
      the lateral geniculate nucleus, and ABD motoneuron activities after
      microinjections of the cholinergic agonist carbachol into the NRPC. RESULTS:
      unilateral microinjections of carbachol in the NRPC induced tonic and phasic
      phenomena in the oculomotor system. Tonic effects consisted of ipsiversive
      rotation to the injected side, convergence, and downward rotation of the eyes.
      Phasic effects consisted of bursts of rhythmic rapid eye movements directed
      contralaterally to the injected side along with PGO-like waves in the lateral
      geniculate and ABD nuclei. Although tonic effects were dependent on the level of
      drowsiness, phasic effects were always present and appeared along with normal
      saccades when the animal was vigilant. ABD motoneurons showed phasic activities
      associated with ABD PGO-like waves during bursts of rapid eye movements, and
      tonic and phasic activities related to eye position and velocity during
      alertness. CONCLUSION: the cholinergic activation of the NRPC induces oculomotor
      phenomena that are somewhat similar to those described during REM sleep. A
      precise comparison of the dynamics and timing of the eye movements further
      suggests that a temporal organization of both NRPCs is needed to reproduce the
      complexity of the oculomotor behavior during REM sleep.

PMID- 21102995
TI  - Motor unit recruitment in human genioglossus muscle in response to hypercapnia.
AB  - STUDY OBJECTIVES: single motor unit recordings of the genioglossus (GG) muscle
      indicate that GG motor units have a variety of discharge patterns, including
      units that have higher discharge rates during inspiration (inspiratory phasic and
      inspiratory tonic), or expiration (expiratory phasic and expiratory tonic), or do
      not modify their rate with respiration (tonic). Previous studies have shown that
      an increase in GG muscle activity is a consequence of increased activity in
      inspiratory units. However, there are differences between studies as to whether
      this increase is primarily due to recruitment of new motor units (motor unit
      recruitment) or to increased discharge rate of already active units (rate
      coding). Sleep-wake state studies in humans have suggested the former, while
      hypercapnia experiments in rats have suggested the latter. In this study, we
      investigated the effect of hypercapnia on GG motor unit activity in humans during
      wakefulness. SETTING: sleep research laboratory. PARTICIPANTS: sixteen healthy
      men. MEASUREMENTS AND RESULTS: each participant was administered at least 6
      trials with P(et)CO(2) being elevated 8.4 (SD = 1.96) mm Hg over 2 min following
      a 30-s baseline. Subjects were instrumented for GG EMG and respiratory
      measurements with 4 fine wire electrodes inserted subcutaneously into the muscle.
      One hundred forty-one motor units were identified during the baseline: 47% were
      inspiratory modulated, 29% expiratory modulated, and 24% showed no respiratory
      related modulation. Sixty-two new units were recruited during hypercapnia. The
      distribution of recruited units was significantly different from the baseline
      distribution, with 84% being inspiratory modulated (P < 0.001). Neither units
      active during baseline, nor new units recruited during hypercapnia, increased
      their discharge rate as P(et)CO(2) increased (P > 0.05 for all comparisons).
      CONCLUSIONS: increased GG muscle activity in humans occurs because of recruitment
      of previously inactive inspiratory modulated units.

PMID- 21102996
TI  - Reliability and validity of the brief insomnia questionnaire in the America
      insomnia survey.
AB  - STUDY OBJECTIVES: to evaluate the reliability and validity of the Brief Insomnia
      Questionnaire (BIQ), a fully structured questionnaire developed to diagnose
      insomnia according to hierarchy-free Diagnostic and Statistical Manual, Fourth
      Edition, Text Revision (DSM-IV-TR), International Classification of Diseases-10
      (ICD-10), and research diagnostic criteria/International Classification of Sleep
      Disorders-2 (RDC/ICSD-2) general criteria without organic exclusions in the
      America Insomnia Survey (AIS). DESIGN: probability subsamples of AIS respondents,
      oversampling BIQ positives, completed short-term test-retest interviews (n = 59)
      or clinical reappraisal interviews (n = 203) to assess BIQ reliability and
      validity. SETTING: the AIS is a large (n = 10,094) epidemiologic survey of the
      prevalence and correlates of insomnia. PARTICIPANTS: adult subscribers to a
      national managed healthcare plan. INTERVENTION: None MEASUREMENTS AND RESULTS:
      BIQ test-retest correlations were 0.47-0.94 for nature of the sleep problems
      (initiation, maintenance, nonrestorative sleep [NRS]), 0.72-0.95 for problem
      frequency, 0.66-0.88 for daytime impairment/distress, and 0.62 for duration of
      sleep. Good individual-level concordance was found between BIQ diagnoses and
      diagnoses based on expert interviews for meeting hierarchy-free inclusion
      criteria for diagnoses in any of the diagnostic systems, with area under the
      receiver operating characteristic curve (AUC, a measure of classification
      accuracy insensitive to disorder prevalence) of 0.86 for dichotomous
      classifications. The AUC increased to 0.94 when symptom-level data were added to
      generate continuous predicted-probability of diagnosis measures. The AUC was
      lower for dichotomous classifications based on RDC/ICSD-2 (0.68) and ICD-10
      (0.70) than for DSM-IV-TR (0.83) criteria but increased consistently when symptom
      level data were added to generate continuous predicted-probability measures of
      RDC/ICSD-2, ICD-10, and DSM-IV-TR diagnoses (0.92-0.95). CONCLUSIONS: these
      results show that the BIQ generates accurate estimates of the prevalence and
      correlates of hierarchy-free insomnia in the America Insomnia Survey.

PMID- 21102997
TI  - Efficacy and Safety of Doxepin 1 mg and 3 mg in a 12-week Sleep Laboratory and
      Outpatient Trial of Elderly Subjects with Chronic Primary Insomnia.
AB  - STUDY OBJECTIVES: to evaluate the efficacy and safety of doxepin 1 mg and 3 mg in
      elderly subjects with chronic primary insomnia. DESIGN AND METHODS: the study was
      a randomized, double-blind, parallel-group, placebo-controlled trial. Subjects
      meeting DSM-IV-TR criteria for primary insomnia were randomized to 12 weeks of
      nightly treatment with doxepin (DXP) 1 mg (n = 77) or 3 mg (n = 82), or placebo
      (PBO; n = 81). Efficacy was assessed using polysomnography (PSG), patient
      reports, and clinician ratings. Objective efficacy data are reported for Nights
      (N) 1, 29, and 85; subjective efficacy data during Weeks 1, 4, and 12; and
      Clinical Global Impression (CGI) scale and Patient Global Impression (PGI) scale
      data after Weeks 2, 4, and 12 of treatment. Safety assessments were conducted
      throughout the study. RESULTS: DXP 3 mg led to significant improvement versus PBO
      on N1 in wake time after sleep onset (WASO; P < 0.0001; primary endpoint), total
      sleep time (TST; P < 0.0001), overall sleep efficiency (SE; P < 0.0001), SE in
      the last quarter of the night (P < 0.0001), and SE in Hour 8 (P < 0.0001). These
      improvements were sustained at N85 for all variables, with significance
      maintained for WASO, TST, overall SE, and SE in the last quarter of the night.
      DXP 3 mg significantly improved patient-reported latency to sleep onset (Weeks 1,
      4, and 12), subjective TST (Weeks 1, 4, and 12), and sleep quality (Weeks 1, 4,
      and 12). Several global outcome-related variables were significantly improved,
      including the severity and improvement items of the CGI (Weeks 2, 4, and 12), and
      all 5 items of the PGI (Week 12; 4 items after Weeks 2 and 4). Significant
      improvements were observed for DXP 1 mg for several measures including WASO, TST,
      overall SE, and SE in the last quarter of the night at several time points. Rates
      of discontinuation were low, and the safety profiles were comparable across the 3
      treatment groups. There were no significant next-day residual effects;
      additionally, there were no reports of memory impairment, complex sleep
      behaviors, anticholinergic effects, weight gain, or increased appetite.
      CONCLUSIONS: DXP 1 mg and 3 mg administered nightly to elderly chronic insomnia
      patients for 12 weeks resulted in significant and sustained improvements in most
      endpoints. These improvements were not accompanied by evidence of next-day
      residual sedation or other significant adverse effects. DXP also demonstrated
      improvements in both patient- and physician-based ratings of global insomnia
      outcome. The efficacy of DXP at the doses used in this study is noteworthy with
      respect to sleep maintenance and early morning awakenings given that these are
      the primary sleep complaints of the elderly. This study, the longest placebo
      controlled, double-blind, polysomnographic trial of nightly pharmacotherapy for
      insomnia in the elderly, provides the best evidence to date of the sustained
      efficacy and safety of an insomnia medication in older adults.

PMID- 21102998
TI  - Alterations in cyclic alternating pattern associated with phase advanced sleep
      are differentially modulated by gaboxadol and zolpidem.
AB  - OBJECTIVE: to evaluate cyclic alternating pattern (CAP) in a phase advance model
      of transient insomnia and the effects of gaboxadol and zolpidem. DESIGN: a
      randomized, double-blind, cross-over study in which habitual sleep time was
      advanced by 4 h. SETTING: 6 sleep research laboratories in US PARTICIPANTS: 55
      healthy subjects (18-57 y) INTERVENTIONS: Gaboxadol 15 mg (GBX), zolpidem 10 mg
      (ZOL), and placebo (PBO). MEASUREMENTS: routine polysomnographic (PSG) measures,
      CAP, spectral power density, and self-reported sleep measures RESULTS: The phase
      advance model of transient insomnia produced significant changes in CAP
      parameters. Both GBX and ZOL significantly and differentially modified CAP
      parameters in the direction of more stable sleep. GBX brought the CAP rate in
      stage 1 sleep and slow wave sleep (SWS) closer to baseline levels but did not
      significantly change the CAP rate in stage 2. ZOL reduced the CAP rate in stage 2
      to near baseline levels, whereas the CAP rate in stage 1 and SWS was reduced
      substantially below baseline levels. The CAP parameter A1 index (associated with
      SWS and sleep continuity) showed the highest correlation with self-reported sleep
      quality, higher than any traditional PSG, spectral, or other self-reported
      measures. CONCLUSION: disruptions in CAP produced by phase advanced sleep were
      significantly and differentially modulated by gaboxadol and zolpidem. The
      relative independence of CAP parameters from other electrophysiological measures
      of sleep, their high sensitivity to sleep disruption, and their strong
      association with subjective sleep quality suggest that CAP variables may serve as
      valuable endpoints in future insomnia research.

PMID- 21103001
TI  - Response to "Biased Corrections or Biased About Corrections"

PMID- 21102999
TI  - Characterization of a novel SOD-1(G93A) transgenic mouse line with very
      decelerated disease development.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease, characterized
      by progressive weakness, muscle wasting and death ensuing 3-5 years after
      diagnosis. The etiology of ALS is complex and therapeutic approaches rely mostly
      on transgenic animal models with SOD-1 mutations. Most frequently employed is a
      mouse line transgenic for SOD-1 (SOD-1 Tg) that contains a point mutation at
      amino acid position 93 (G->A), present in patients suffering from a familial form
      of amyotrophic lateral sclerosis. Here we report on a SOD-1 (G93A) Tg mouse line
      with abnormally delayed onset of disease and prolonged survival. This phenotype
      arose spontaneously in our colony of the classic SOD-1 (G93A) line. We found that
      the copy number of the SOD-1 transgene was drastically decreased. We established
      a new breeding colony, the SOD-1 (G93A)(PS) line (PS for prolonged survival)
      where the phenotype is stably inherited for 4 generations now. The mice develop
      symptoms at an age of approximately 12 months and die at 15 months of age. The
      delayed development of disease may more closely mimic human pathophysiology, and
      studying drug effects in this model may yield added confidence for potential
      efficacy of ALS drug candidates.

PMID- 21103002
TI  - Three-pulse photon echo peak shift spectroscopy as a probe of flexibility and
      conformational heterogeneity in protein folding.
AB  - We investigate the equilibrium unfolding of Zn-cytochrome c in guanidine
      hydrochloride by three-pulse photon echo peak shift (3PEPS) spectroscopy.
      Unexpectedly, the measurements reveal that inhomogeneous broadening of the sample
      at the midpoint of the denaturation is larger than that of either native or
      unfolded states. To interpret this finding, we present simulations of the peak
      shift for both two-state and three-state unfolding models. Both the denaturant
      concentration dependence of the asymptotic peak shift (APS) and the wavelength
      dependence of the APS at the midpoint of the denaturation are different for the
      two models. Our data are consistent with two-state unfolding.

PMID- 21103003
TI  - p97-containing complexes in proliferation control and cancer: emerging culprits
      or guilt by association?
AB  - p97 (also called VCP in metazoans and CDC48 in yeast) is a highly conserved,
      abundant and essential type II ATPase that functions in numerous ubiquitin
      signaling dependent processes. p97/Cd48 activities require a growing number of
      adaptor or accessory proteins that promote interactions with ubiquitinated
      proteins. p97 has human disease relevance as it is mutated in familial cases of
      inclusion body myopathy associated with Paget's disease of the bone and
      frontotemporal dementia (IBMPFD). There is also increasing evidence suggesting
      that p97 and/or some of its adaptors play a role in cancer. This review will
      summarize our existing knowledge of the biochemical, molecular and cellular
      activities of p97-containing complexes, with an ending focus on their potential
      role in malignancy.

PMID- 21103004
TI  - Small RING Finger Proteins RBX1 and RBX2 of SCF E3 Ubiquitin Ligases: The Role in
      Cancer and as Cancer Targets.
AB  - The SCF (Skp1-cullin-F-box proteins), also known as CRL (cullin-based RING
      ligase), is the largest family of E3 ubiquitin ligases that mediate approximately
      20% ubiquitinated protein substrates for 26S proteasome degradation. Through
      promoting timely degradation of many key regulatory proteins, SCF E3 ligase
      controls numerous cellular processes; its dysfunction contributes to a number of
      human diseases, including cancer. The RING component of SCF complex consists of 2
      family members, RBX1 (RING box protein 1), also known as ROC1 (regulator of
      cullins), and RBX2/ROC2 (also known as SAG [sensitive to apoptosis gene]), both
      of which are essential for the catalytic activity of SCF. RBX1 and RBX2 are
      evolutionarily conserved from yeast to humans and play an essential role during
      mouse embryonic development. Moreover, RBX1 and RBX2 are both overexpressed in
      multiple human cancer tissues and required for the growth and survival of cancer
      cells. In this review, we will discuss the similarities and differences between 2
      RING family members, their regulation of SCF E3 ligase activity, and their role
      in development, cancer cell survival, and skin carcinogenesis, along with a brief
      discussion of RBX-SCF E3 ligases as the cancer targets and a recently discovered
      small molecule inhibitor of SCF E3 ligases as a novel class of anticancer drugs.

PMID- 21103006
TI  - From bad to worse: striatal coding of the relative value of painful decisions.
AB  - The majority of decision-related research has focused on how the brain computes
      decisions over outcomes that are positive in expectation. However, much less is
      known about how the brain integrates information when all possible outcomes in a
      decision are negative. To study decision-making over negative outcomes, we used
      fMRI along with a task in which participants had to accept or reject 50/50
      lotteries that could result in more or fewer electric shocks compared to a
      reference amount. We hypothesized that behaviorally, participants would treat
      fewer shocks from the reference amount as a gain, and more shocks from the
      reference amount as a loss. Furthermore, we hypothesized that this would be
      reflected by a greater BOLD response to the prospect of fewer shocks in regions
      typically associated with gain, including the ventral striatum and orbitofrontal
      cortex. The behavioral data suggest that participants in our study viewed all
      outcomes as losses, despite our attempt to induce a status quo. We find that the
      ventral striatum showed an increase in BOLD response to better potential gambles
      (i.e., fewer expected shocks). This lends evidence to the idea that the ventral
      striatum is not solely responsible for reward processing but that it might also
      signal the relative value of an expected outcome or action, regardless of whether
      the outcome is entirely appetitive or aversive. We also find a greater response
      to worse gambles in regions previously associated with aversive valuation,
      suggesting an opposing but simultaneous valuation signal to that conveyed by the
      striatum.

PMID- 21103007
TI  - Probing different time-scales of oscillatory fluctuations in visual awareness:
      from behavior to phase.

PMID- 21103005
TI  - Neurogenetic effects on cognition in aging brains: a window of opportunity for
      intervention?
AB  - Knowledge of genetic influences on cognitive aging can constrain and guide
      interventions aimed at limiting age-related cognitive decline in older adults.
      Progress in understanding the neural basis of cognitive aging also requires a
      better understanding of the neurogenetics of cognition. This selective review
      article describes studies aimed at deriving specific neurogenetic information
      from three parallel and interrelated phenotype-based approaches: psychometric
      constructs, cognitive neuroscience-based processing measures, and brain imaging
      morphometric data. Developments in newer genetic analysis tools, including genome
      wide association, are also described. In particular, we focus on models for
      establishing genotype-phenotype associations within an explanatory framework
      linking molecular, brain, and cognitive levels of analysis. Such multiple
      phenotype approaches indicate that individual variation in genes central to
      maintaining synaptic integrity, neurotransmitter function, and synaptic
      plasticity are important in affecting age-related changes in brain structure and
      cognition. Investigating phenotypes at multiple levels is recommended as a means
      to advance understanding of the neural impact of genetic variants relevant to
      cognitive aging. Further knowledge regarding the mechanisms of interaction
      between genetic and preventative procedures will in turn help in understanding
      the ameliorative effect of various experiential and lifestyle factors on age
      related cognitive decline.

PMID- 21103008
TI  - Are Bipolar Disorder and Schizophrenia Neuroanatomically Distinct? An Anatomical
      Likelihood Meta-analysis.
AB  - OBJECTIVE: There is renewed debate on whether modern diagnostic classification
      should adopt a dichotomous or dimensional approach to schizophrenia and bipolar
      disorder. This study synthesizes data from voxel-based studies of schizophrenia
      and bipolar disorder to estimate the extent to which these conditions have a
      common neuroanatomical phenotype. METHODS: A post-hoc meta-analytic estimation of
      the extent to which bipolar disorder, schizophrenia, or both conditions
      contribute to brain gray matter differences compared to controls was achieved
      using a novel application of the conventional anatomical likelihood estimation
      (ALE) method. 19 schizophrenia studies (651 patients and 693 controls) were
      matched as closely as possible to 19 bipolar studies (540 patients and 745
      controls). RESULT: Substantial overlaps in the regions affected by schizophrenia
      and bipolar disorder included regions in prefrontal cortex, thalamus, left
      caudate, left medial temporal lobe, and right insula. Bipolar disorder and
      schizophrenia jointly contributed to clusters in the right hemisphere, but
      schizophrenia was almost exclusively associated with additional gray matter
      deficits (left insula and amygdala) in the left hemisphere. LIMITATION: The
      current meta-analytic method has a number of constraints. Importantly, only
      studies identifying differences between controls and patient groups could be
      included in this analysis. CONCLUSION: Bipolar disorder shares many of the same
      brain regions as schizophrenia. However, relative to neurotypical controls, lower
      gray matter volume in schizophrenia is more extensive and includes the amygdala.
      This fresh application of ALE accommodates multiple studies in a relatively
      unbiased comparison. Common biological mechanisms may explain the neuroanatomical
      overlap between these major disorders, but explaining why brain differences are
      more extensive in schizophrenia remains challenging.

PMID- 21103010
TI  - The Saccadic Re-Centering Bias is Associated with Activity Changes in the Human
      Superior Colliculus.
AB  - Being able to effectively explore our visual world is of fundamental importance,
      and it has been suggested that the straight-ahead gaze (primary position) might
      play a special role in this context. We employed fMRI in humans to investigate
      how neural activity might be modulated for saccades relative to this putative
      default position. Using an endogenous cueing paradigm, saccade direction and
      orbital starting position were systematically manipulated, resulting in saccades
      toward primary position (centripetal) and away from primary position
      (centrifugal) that were matched in amplitude, directional predictability, as well
      as orbital starting position. In accord with earlier research, we found that fMRI
      activity in the superior colliculus (SC), as well as in the frontal eye fields
      and the intraparietal sulcus, was enhanced contralateral to saccade direction
      across all saccade conditions. Furthermore, the SC exhibited a relative activity
      decrease during re-centering relative to centrifugal saccades, a pattern that was
      paralleled by faster saccadic reaction times. In contrast, activity within the
      cortical eye fields was not significantly modulated during re-centering saccades
      as compared to other saccade types, suggesting that the re-centering bias is
      predominantly implemented at a subcortical rather than cortical processing stage.
      Such a modulation might reflect a special coding bias facilitating the return of
      gaze to a default position in the gaze space in which retinotopic and egocentric
      reference frames are aligned and from which the visual world can be effectively
      explored.

PMID- 21103011
TI  - The Grandest Genetic Experiment Ever Performed on Man? - A Y-Chromosomal
      Perspective on Genetic Variation in India.
AB  - We have analysed Y-chromosomal data from Indian caste, Indian tribal and East
      Asian populations in order to investigate the impact of the caste system on male
      genetic variation. We find that variation within populations is lower in India
      than in East Asia, while variation between populations is overall higher. This
      observation can be explained by greater subdivision within the Indian population,
      leading to more genetic drift. However, the effect is most marked in the tribal
      populations, and the level of variation between caste populations is similar to
      the level between Chinese populations. The caste system has therefore had a
      detectable impact on Y-chromosomal variation, but this has been less strong than
      the influence of the tribal system, perhaps because of larger population sizes in
      the castes, more gene flow or a shorter period of time.

PMID- 21103012
TI  - The New Inhibitor of Monoamine Oxidase, M30, has a Neuroprotective Effect Against
      Dexamethasone-Induced Brain Cell Apoptosis.
AB  - Stress detrimentally affects the brain and body and can lead to or be accompanied
      by depression. Although stress and depression may contribute to each other, the
      exact molecular mechanism underlying the effects is unclear. However, there is a
      correlation between stress and an increase in glucocorticoid secretion which
      causes a subsequent increase in monoamine oxidase (MAO) activity during stress.
      Consequently, MAO inhibitors have been used as traditional antidepressant drugs.
      Cellular treatment with the synthetic glucocorticoid, dexamethasone (a cellular
      stressor), has been reported to markedly increase both MAO A and MAO B catalytic
      activities, as well as apoptosis. This study compares the neuroprotective
      abilities of M30 (a new generation inhibitor of both MAO A and MAO B) with
      rasagiline (Azilect((r)), another new MAO B inhibitor) and selegiline
      (Deprenyl((r)), a traditional MAO B inhibitor) in the prevention of dexamethasone
      induced brain cell death and MAO activity in human neuroblastoma cells, SH-SY5Y.
      M30 demonstrated the highest inhibitory effect on MAO A; however, M30 showed the
      lowest inhibitory effect on MAO B enzymatic activity in comparison to rasagiline
      and selegiline. Although, M30 exhibited the greatest neuroprotective effect by
      decreasing cell death rates and apoptotic DNA damage compared to rasagiline and
      selegiline, these neuroprotective effects of M30 were, overall, similar to
      rasagiline. Summarily, M30 has a generally greater impact on neuroprotection than
      the MAO B inhibitors, selegiline and rasagiline. Our results suggest that M30 may
      have great potential in alleviating disorders involving increases in both MAO A
      and MAO B, such as stress-induced disorders.

PMID- 21103013
TI  - Mechanisms for Phase Shifting in Cortical Networks and their Role in
      Communication through Coherence.
AB  - In the primate visual cortex, the phase of spikes relative to oscillations in the
      local field potential (LFP) in the gamma frequency range (30-80 Hz) can be
      shifted by stimulus features such as orientation and thus the phase may carry
      information about stimulus identity. According to the principle of communication
      through coherence (CTC), the relative LFP phase between the LFPs in the sending
      and receiving circuits affects the effectiveness of the transmission. CTC
      predicts that phase shifting can be used for stimulus selection. We review and
      investigate phase shifting in models of periodically driven single neurons and
      compare it with phase shifting in models of cortical networks. In a single
      neuron, as the driving current is increased, the spike phase varies
      systematically while the firing rate remains constant. In a network model of
      reciprocally connected excitatory (E) and inhibitory (I) cells phase shifting
      occurs in response to both injection of constant depolarizing currents and to
      brief pulses to I cells. These simple models provide an account for phase
      shifting observed experimentally and suggest a mechanism for implementing CTC. We
      discuss how this hypothesis can be tested experimentally using optogenetic
      techniques.

PMID- 21103014
TI  - Strategies for the study of neuropsychiatric disorders using endophenotypes in
      developing countries: a potential databank from china.
AB  - Endophenotypic research can be considered to be one of the most promising
      strategies to bridge the gap between genomic complexity and the phenotypic
      heterogeneity observed in neuropsychiatric disorders. However, despite the
      promising and systematic work initiated by our western counterparts, this
      research strategy is still not well known in developing countries. Thus, the
      purpose of this paper is to argue the merits and promise of a potentially useful
      database on phenotypes and endophenotypes for developing countries.

PMID- 21103009
TI  - Extrastriatal dopaminergic circuits of the Basal Ganglia.
AB  - The basal ganglia are comprised of the striatum, the external and internal
      segment of the globus pallidus (GPe and GPi, respectively), the subthalamic
      nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and
      SNr, respectively). Dopamine has long been identified as an important modulator
      of basal ganglia function in the striatum, and disturbances of striatal
      dopaminergic transmission have been implicated in diseases such as Parkinson's
      disease (PD), addiction and attention deficit hyperactivity disorder. However,
      recent evidence suggests that dopamine may also modulate basal ganglia function
      at sites outside of the striatum, and that changes in dopaminergic transmission
      at these sites may contribute to the symptoms of PD and other neuropsychiatric
      disorders. This review summarizes the current knowledge of the anatomy,
      functional effects and behavioral consequences of the dopaminergic innervation to
      the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of
      basal ganglia function at extrastriatal sites may provide us with opportunities
      to develop new and more specific strategies for treating disorders of basal
      ganglia dysfunction.

PMID- 21103015
TI  - Impaired Social Behavior in 5-HT(3A) Receptor Knockout Mice.
AB  - The 5-HT(3) receptor is a ligand-gated ion channel expressed on interneurons
      throughout the brain. So far, analysis of the 5-HT(3A) knockout mouse revealed
      changes in nociceptive processing and a reduction in anxiety related behavior.
      Recently, it was shown that the 5-HT(3) receptor is also expressed on Cajal
      Retzius cells which play a key role in cortical development and that knockout
      mice lacking this receptor showed aberrant growth of the dendritic tree of
      cortical layer II/III pyramidal neurons. Other mouse models in which serotonergic
      signaling was disrupted during development showed similar morphological changes
      in the cortex, and in addition, also deficits in social behavior. Here, we
      subjected male and female 5-HT(3A) knockout mice and their non-transgenic
      littermates to several tests of social behavior. We found that 5-HT(3A) knockout
      mice display impaired social communication in the social transmission of food
      preference task. Interestingly, we showed that in the social interaction test
      only female 5-HT(3A) knockout mice spent less time in reciprocal social
      interaction starting after 5 min of testing. Moreover, we observed differences in
      preference for social novelty for male and female 5-HT(3A) knockout mice during
      the social approach test. However, no changes in olfaction, exploratory activity
      and anxiety were detected. These results indicate that the 5-HT(3A) knockout
      mouse displays impaired social behavior with specific changes in males and
      females, reminiscent to other mouse models in which serotonergic signaling is
      disturbed in the developing brain.

PMID- 21103016
TI  - A novel synthesis of 3-(substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)-diones.
AB  - An improved synthesis of 3-(substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)
      diones, a known subclass of 4-deazatoxoflavins, is reported. The approach
      involves treatment of 3-methyl-6-(1-methylhydrazinyl) uracil with representative
      phenyl and alkyl glyoxal monohydrates, which in turn are obtained by selenium
      dioxide oxidation of the corresponding phenyl and alkyl methyl ketones. The first
      entry into 4-monosubstituted isomers is also reported.

PMID- 21103017
TI  - Rebuilding cerebellar network computations from cellular neurophysiology.

PMID- 21103018
TI  - Patterned Activity within the Local Cortical Architecture.
AB  - The cerebral cortex is a vastly complex structure consisting of multiple distinct
      populations of neurons residing in functionally specialized cortical
      compartments. A fundamental goal in systems neuroscience is to understand the
      interactions among cortical neurons and their relationship to behavior. It is
      hypothesized that dynamic activity patterns, such as oscillations in global
      neuronal activity, could span large, heterogeneous populations of cortical
      neurons in such a manner as to bind together the activity of otherwise disparate
      cortical networks. Little is known about the mechanisms by which such global
      oscillatory patterns entrain cortical networks, or the contribution of such
      activity patterns to cortical function. An important step toward elucidating the
      role of such patterned activity in cortical information processing is
      understanding these interactions at the local circuit level. Here, we highlight
      recent findings that provide insight into how dynamic activity patterns affect
      specific neuronal populations and circuits.

PMID- 21103019
TI  - Are different rhythms good for different functions?
AB  - This essay discusses the relationship between the physiology of rhythms and
      potential functional roles. We focus on how the biophysics underlying different
      rhythms can give rise to different abilities of a network to form and manipulate
      cell assemblies. We also discuss how changes in the modulatory setting of the
      rhythms can change the flow of information through cortical circuits, again tying
      physiology to computation. We suggest that diverse rhythms, or variations of a
      rhythm, can support different components of a cognitive act, with multiple
      rhythms potentially playing multiple roles.

PMID- 21103020
TI  - Gaining Efficiency via Weighted Estimators for Multivariate Failure Time Data*
AB  - Multivariate failure time data arise frequently in survival analysis. A commonly
      used technique is the working independence estimator for marginal hazard models.
      Two natural questions are how to improve the efficiency of the working
      independence estimator and how to identify the situations under which such an
      estimator has high statistical efficiency. In this paper, three weighted
      estimators are proposed based on three different optimal criteria in terms of the
      asymptotic covariance of weighted estimators. Simplified close-form solutions are
      found, which always outperform the working independence estimator. We also prove
      that the working independence estimator has high statistical efficiency, when
      asymptotic covariance of derivatives of partial log-likelihood functions is
      nearly exchangeable or diagonal. Simulations are conducted to compare the
      performance of the weighted estimator and working independence estimator. A data
      set from Busselton population health surveys is analyzed using the proposed
      estimators.

PMID- 21103022
TI  - Hoping, Willing, and Narrative Re-Envisioning.
AB  - At first glance, hoping and willing do not seem to have much to do with one
      another. They evoke quite disparate turns of mind, in fact. Hope, which Aristotle
      called a "waking dream," is associated with imagination, daydreams, and wishful
      thinking. Willing, on the other hand, is aligned with practical effort,
      discipline, and acting against one's inclinations. Despite their lack of obvious
      affinity, in some communities-especially in the face of extreme suffering-the two
      acts may develop a close kinship. Hope as a moral task, even a narrative quest,
      can demand the arduous cultivation of the will. Hope is not necessarily something
      people easily acquire-not a matter of mere wishful thinking when life becomes
      difficult, but a difficult moral obligation that must be assumed as a way to
      confront pain and despair.

PMID- 21103023
TI  - A SEMIPARAMETRIC MODEL FOR CLUSTER DATA.
AB  - In the analysis of cluster data the regression coefficients are frequently
      assumed to be the same across all clusters. This hampers the ability to study the
      varying impacts of factors on each cluster. In this paper, a semiparametric model
      is introduced to account for varying impacts of factors over clusters by using
      cluster-level covariates. It achieves the parsimony of parametrization and allows
      the explorations of nonlinear interactions. The random effect in the
      semiparametric model accounts also for within cluster correlation. Local linear
      based estimation procedure is proposed for estimating functional coefficients,
      residual variance, and within cluster correlation matrix. The asymptotic
      properties of the proposed estimators are established and the method for
      constructing simultaneous confidence bands are proposed and studied. In addition,
      relevant hypothesis testing problems are addressed. Simulation studies are
      carried out to demonstrate the methodological power of the proposed methods in
      the finite sample. The proposed model and methods are used to analyse the second
      birth interval in Bangladesh, leading to some interesting findings.

PMID- 21103021
TI  - Ambient experience in restitutive treatment of aphasia.
AB  - One of the greatest challenges to language rehabilitation is reconciling the fact
      that the same therapeutic intervention, provided to different individuals with
      similar types of stroke-induced aphasia, may result in divergent outcomes. In
      this paper, the authors reviewed existing literature to identify relevant ambient
      factors - those outside the control of the clinician - that may potentially
      influence functional language recovery in aphasia and response to treatment. The
      goal was to develop a clinical history-taking tool to assist clinicians in
      gathering information germane to each individual's unique circumstances and
      environment, elements that may have previously been underestimated, to provide a
      complete inventory of potentially potent prognostic factors. First, two of the
      authors, speech-language pathologists experienced in aphasia rehabilitation,
      identified and categorized factors that seemed likely to influence aphasia
      outcomes. Then, a wide range of literature was reviewed in an effort to identify
      factors empirically found to be potent influences on aphasia recovery. Where
      studies relating these factors to aphasia were not found, relevant research from
      allied fields that examined recovery from brain injury is reported. Moreover,
      some factors thought to be potentially potent have yet to be examined. Finally,
      the ambient factors supported by evidence were categorized as facilitators or
      barriers to functional improvement, and the Ambient Influences on Outcome
      Checklist (AOC) was developed, including only those factors shown to be potent in
      the recovery process. It is hoped that this checklist can be used to more broadly
      assess potential prognostic influences in aphasia restitution, as well as spawn
      further research.

PMID- 21103024
TI  - Synthetic Utility of Epoxides for Chiral Functionalization of Isoxazoles.
AB  - The lithio-anion of isoxazole 2 was found to ring open propylene oxide in good
      yields with complete regioselectivity. Vinylic and benzylic epoxides were
      utilized as key examples of electrophiles and found to produce a mixture of
      regioisomeric adducts. Additionally, the use of chiral epoxides was explored, and
      absolute configuration was determined by X-ray crystallography to prove that
      nucleophilic attack at the benzylic carbon of (R)-styrene oxide proceeds with
      100% inversion at the benzylic carbon to afford the (S)-alcohol (4b).

PMID- 21103025
TI  - Metal Nanoparticle/Block Copolymer Composite Assembly and Disassembly.
AB  - Ligand-stabilized platinum nanoparticles (Pt NPs) were self-assembled with
      poly(isoprene-block-dimethylaminoethyl methacrylate) (PI-b-PDMAEMA) block
      copolymers to generate organic-inorganic hybrid materials. High loadings of NPs
      in hybrids were achieved through usage of N,N-di-(2-(allyloxy)ethyl)-N-3
      mercaptopropyl-N-3-methylammonium chloride as the ligand, which provided high
      solubility of NPs in various solvents as well as high affinity to PDMAEMA. From
      NP synthesis, existence of sub-1 nm Pt NPs was confirmed by high-angle annular
      dark field scanning transmission electron microscopy (HAADF-STEM) images.
      Estimations of the Pt NP ligand head group density based on HAADF-STEM images and
      thermogravimetric analysis (TGA) data yielded results comparable to what has been
      found for alkanethiol self-assembled monolayers (SAMs) on flat Pt {111} surfaces.
      Changing the volume fraction of Pt NPs in block copolymer-NP composites yielded
      hybrids with spherical micellar, wormlike micellar, lamellar and inverse
      hexagonal morphologies. Disassembly of hybrids with spherical, wormlike micellar,
      and lamellar morphologies generated isolated metal-NP based nano-spheres,
      cylinders and sheets, respectively. Results suggest the existence of powerful
      design criteria for the formation of metal-based nanostructures from designer
      blocked macromolecules.

PMID- 21103026
TI  - Structure Effect on Antioxidant Activity of Catecholamines toward Singlet Oxygen
      and Other Reactive Oxygen Species in vitro.
AB  - The reactivity of catecholamine neurotransmitters and the related metabolites
      were precisely investigated toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals
      and reactive oxygen species. Catecholamines reacted immediately with DPPH
      radicals, their reactivity being stronger than that of ascorbic acid as a
      reference. Superoxide scavenging activities of catecholamines determined by WST-1
      and electron spin resonance (ESR) spin trapping methods were also high. Whereas
      tyrosine, the dopamine precursor showed no reactivity toward superoxide. The
      reactivity toward singlet oxygen was evaluated by observing specific photon
      emission from singlet oxygen. The results revealed that reactivity of
      catecholamines was markedly higher than that of sodium azide, and catechin as
      catechol reference. The reaction of catecholamines and singlet oxygen was further
      studied by ESR using 55-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping
      reagent and rose bengal as photosensitizer. DMPO-OH signal of epinephrine was
      significantly small compared to other catecholamines, catechin, and 4
      methylcatechol as a reference compound and was as small as that of tyrosine. The
      signal formation was totally dependent on singlet oxygen, and the presence of
      catechol compounds. These results indicated that epinephrine is the most potent
      singlet oxygen quencher than other catecholamines, and the secondary amino group
      in its alkyl side chain could play a role in unique singlet oxygen quenching
      property of epinephrine.

PMID- 21103027
TI  - Pregnancy-induced hypertension and preeclampsia: levels of angiogenic factors in
      malaysian women.
AB  - Preeclampsia (PE) is a major contributor to maternal and fetal mortality. The
      cause of preeclampsia remains unclear, but oxidative stress on the endothelium
      leading to endothelial dysfunction is said to be the root cause of the disease.
      The aim of this study was to measure and determine the plasma levels of key
      angiogenic factors in pregnancy as an indicator for the early onset of
      preeclampsia in pregnancy. Plasma levels of circulating a soluble fms like
      tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, vascular endothelial
      growth factor (VEGF) and placental growth factor (PIGF), both pro-angiogenic
      factors were analyzed in normal pregnant Malaysian women (control group, n = 34),
      women with pregnant induced hypertension (PIH, n = 34) and women with
      preeclampsia (PE, n = 34) all at three gestational ages, 24-28 weeks (early
      pregnancy: EP), 32-36 weeks (late pregnancy: LP) and 6 weeks after delivery
      (postpartum: PN). The plasma levels of angiogenic factors were determined by
      ELISA. sFlt-1 levels were elevated in PIH and PE patients as compared to
      controls. PIGF and VEGF were significantly decreased in PIH and PE as compared to
      the controls. These results suggest that elevated concentration of sFlt-1 and
      suppressed levels of PIGF and VEGF may contribute to the development of
      hypertension in pregnancy which precedes preeclampsia.

PMID- 21103028
TI  - A beverage containing fermented black soybean ameliorates ferric
      nitrilotriacetate-induced renal oxidative damage in rats.
AB  - It is beneficial to seek scientific basis for the effects of functional foods.
      Natural pigments derived from plants are widely known as possible antioxidants.
      Black soybean contains a larger amount of anthocyanins than regular soybean. Here
      we studied the antioxidative effect of a beverage obtained via citric acid
      fermentation of black soybean (BBS), using a rat model of renal oxidative injury
      induced by a renal carcinogen, ferric nitrilotriacetate. BBS (10 ml/kg) was
      orally administered 30 min before ferric nitrilotriacetate treatment. Renal lipid
      peroxidation was significantly suppressed in the BBS-pretreated animals
      concomitant with decrease in 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy
      2'-deoxyguanosine. Maintenance of renal activities of antioxidative enzymes
      including catalase, glutathione peroxidase, glutathione reductase, glutathione S
      transferase, glucose-6-phosphate dehydrogenase and quinone reductase was
      significantly better in the BBS-pretreated rats. Elevation of serum creatinine
      and urea nitrogen was significantly suppressed in the BBS-pretreated rats. These
      data suggest that dietary intake of BBS is useful for the prevention of renal
      tubular oxidative damage mediate by iron, and warrant further investigation.

PMID- 21103029
TI  - A Comparative Investigation of an in vitro and Clinical Test of the Bifidogenic
      Effect of an Infant Formula.
AB  - The bifidogenic effect of an infant formula supplemented with inulin and
      fructooligosaccharides (4.0 g/l) was examined clinically and in vitro, and
      compared that of mature breast milk. In a 28-day clinical study, fecal samples of
      21 infants, divided into two groups: one receiving the infant formula and the
      other breast milk, were microbiologically and biochemically examined. In the in
      vitro investigation, microbiological and biochemical changes in the infant
      formula and breast milk induced by the action of bifidobacteria isolated from
      infant feces were examined. There were no significant differences in the fecal
      numbers of lactobacilli, total aerobes, anaerobes or yeasts and fungi. In
      contrast, the bifidobacteria numbers in the stools increased significantly during
      the study in the infants receiving the supplemented formula. The comparative in
      vitro test showed that the bifidogenic effect was similar for infant formula and
      breast milk in terms of the number of bifidobacteria. Consumption of infant
      formula with added inulin and fructooligosaccharides stimulated the bifidogenic
      effect, both clinically and in vitro. The in vitro test can quickly and
      objectively determine the bifidogenic effect of infant formula and indicate their
      quality. However, a clinical test is necessary to determine the acceptance and
      biological value of infant formula.

PMID- 21103030
TI  - Genetic Polymorphisms of Molecules Associated with Innate Immune Responses, TRL2
      and MBL2 Genes in Japanese Subjects with Functional Dyspepsia.
AB  - Inflammatory changes in the gastric mucosa are commonly observed in Japanese
      patients with functional dyspepsia (FD). However, detailed data regarding the
      possible association between the genetic factors of inflammation related
      molecules and FD are not available. Toll like receptor 2 (TLR2) and mannan
      binding lectin (MBL) protein play important roles in the innate immune
      activation. We aimed to clarify the association between common polymorphisms of
      TLR2 and MBL2 genes with FD in Japanese subjects. TLR2 -196 to -174 del and MBL2
      codon54 G/A polymorphisms were genotyped in 111 FD patients according to Rome III
      criteria and 106 asymptomatic controls. Non-significant correlation was found
      between TLR2 and MBL2 polymorphisms with FD. However, in Helicobacter pylori (H.
      pylori) positives, we found significant inverse association between TLR2 -196 to 
      174 del carrier and FD among H. pylori positive subjects (Adjusted odds ratio
      (OR) = 0.48, 95% confidence interval (CI) = 0.23-0.996, p = 0.0488). We also
      found significant inverse association between the same genotype with postprandial
      distress syndrome (PDS) among H. pylori positive subjects (Adjusted OR = 0.22,
      95% CI = 0.07-0.69, p = 0.0099). Our data suggest that TLR2 -196 to -174 del
      carriers's status but not MBL2 codon54 G/A is inversely related to the risk with
      FD in H. pylori-infected subjects.

PMID- 21103031
TI  - Glucocorticoid Generates ROS to Induce Oxidative Injury in the Hippocampus,
      Leading to Impairment of Cognitive Function of Rats.
AB  - The present study attempted to clarify whether over-secretion of glucocorticoids
      in the serum caused by increased hypothalamus-pituitary-adrenal activity induces
      oxidative stress in the rat brain, and how the stress causes the emergence of
      cognitive deficits. When rats were subcutaneously injected with corticosterone,
      lipid hydroperoxides and protein carbonyls increased markedly in the hippocampus
      in association with a decrease in activity of antioxidative enzymes, such as
      superoxide dismutase, catalase and glutathione peroxidase. These results suggest
      that high-level corticosterone in the serum induces reactive oxygen species
      (ROS), leading to oxidative damage in the hippocampus. After administration of
      corticosterone to rats, glucose and superoxide levels in the serum increased
      markedly. Furthermore, pyramidal cell apoptosis was observed to accompany the
      loss of glucocorticoid receptors at the cornus ammonis 1 region of the
      hippocampus. Rats injected with corticosterone showed marked deficits in memory
      function. The present results imply that ROS generated from the glycation
      reaction of increased glucose levels caused by gluconeogenesis activation through
      glucocorticoid with proteins in the serum attack the hippocampus to induce
      neurodegeneration, resulting in cognitive deficits in rats.

PMID- 21103032
TI  - Relationship between Pentosidine and Pyridinoline Levels in Human Diabetic
      Cataract Lenses.
AB  - The relationship between the levels of two different crosslink compounds,
      pentosidine and pyridinoline, in human diabetic cataract lenses was investigated
      to elucidate the pathogenic mechanism of diabetic cataract. Subjects were
      classified into diabetes mellitus (DM) group and non-DM group according to the
      presence or absence of DM. The levels of the crosslink compounds were determined
      using high-performance liquid chromatography and spectrofluorometry after acid
      hydrolysis. In the non-DM group the pentosidine level was significantly and
      positively correlated with the pyridinoline level and age. In the DM group the
      pentosidine level was not significantly correlated with either pyridinoline level
      or age. Pyridinoline levels and age were not significantly correlated in either
      group. The increase in crosslink compounds due to glycation and the relationship
      between the compounds are changed in DM lenses.

PMID- 21103033
TI  - Scavenging effects of dexrazoxane on free radicals.
AB  - Dexrazoxane (ICRF-187) has been clinically used to reduce doxorubicin-induced
      cardiotoxicity for more than 20 years. It has been proposed that dexrazoxane may
      act through its rings-opened hydrolysis product ADR-925, which can either remove
      iron from the iron-doxorubicin complex or bind to free iron, thus preventing iron
      based oxygen radical formation. However, it is not known whether the antioxidant
      actions of dexrazoxane are totally dependent on its metabolization to its rings
      opened hydrolysis product and whether dexrazoxane has any effect on the iron
      independent oxygen free radical production. In this study, we examined the
      scavenging effect of dexrazoxane on hydroxyl, superoxide, lipid, DPPH and ABTS(+)
      free radicals in vitro solution systems. The results demonstrated that
      dexrazoxane was an antioxidant that could effectively scavenge these free
      radicals and the scavenging effects of dexrazoxane did not require the enzymatic
      hydrolysis. In addition, dexrazoxane was capable to inhibit the generation
      superoxide and hydroxyl radicals in iron free reaction system, indicating that
      the antioxidant properties of dexrazoxane were not solely dependent on iron
      chelation. Thus the application of dexrazoxane should not be limited to
      doxorubicin-induced cardiotoxicity. Instead, as an effective antioxidant that has
      been clinically proven safe, dexrazoxane may be used in a broader spectrum of
      diseases that are known to be benefited by antioxidant treatments.

PMID- 21103034
TI  - Soybean-derived phosphatidylserine improves memory function of the elderly
      Japanese subjects with memory complaints.
AB  - Soybean-derived phosphatidylserine (Soy-PS) is a phosphatidylserine made from
      soybean lecithin by enzymatic reaction with L-serine. A double-blind, randomized
      controlled study was conducted to investigate the effects of Soy-PS on the
      cognitive functions of the elderly Japanese subjects with memory complaints.
      Seventy-eight elderly people with mild cognitive impairment (50-69 years old)
      were randomly allocated to take Soy-PS (100 mg, 300 mg/day) or placebo for 6
      months. As a result, there was no difference in blood markers and vital signs
      during Soy-PS treatment and any side effect caused by Soy-PS treatment was not
      observed. Neuropsychological test scores were similarly increased in all groups
      including placebo group. However, in the subjects with relatively low score at
      baseline, the memory scores in PS treated groups were significantly increased
      against the baseline, while those of placebo group remained unchanged. And the
      memory improvements in Soy-PS-treated groups were mostly attributed to the
      increase in delayed verbal recall, a memory ability attenuated in the earliest
      stage of dementia. In conclusion, Soy-PS used in this study is considered as
      safety food ingredient and 6 months of Soy-PS supplementation could improve the
      memory functions of the elderly with memory complaints.

PMID- 21103035
TI  - Small bowel tissue concentration of rebamipide: study of two dosages in healthy
      subjects.
AB  - Non-steroidal anti-inflammatory drug (NSAID)-related small intestinal
      complications exist, since developed new diagnostic modalities, such as balloon
      and capsule endoscopies. Some experiments have shown rebamipide to protect from
      NSAID-induced small intestinal complications. The purpose of this study is to
      investigate whether the effective concentrations of rebamipide (COR) are present
      in the small intestine after taking an ordinary clinical dose and double dose of
      this drug. Twelve healthy male subjects were enrolled. After taking 100 or 200 mg
      of rebamipide, balloon enteroscopy was performed at 1 and 3 h, and biopsy samples
      were obtained from the jejunum and the stomach. Venous blood samples were taken
      simultaneously. Samples were analyzed by high-performance liquid chromatography.
      The mean COR in the jejunum was higher than 100 uM at 1 h and higher than 10 uM
      at 3 h in both the 100 and 200 mg groups. Mean COR in the stomach was less than
      100 uM at 1 h in the 100 mg group; however it was higher than 100 uM in the 200
      mg group. In conclusion, the COR level in the jejunum was sufficient to protect
      for NSAID-induced gastrointestinal complications.

PMID- 21103036
TI  - Increased pulse wave velocity reflecting arterial stiffness in patients with
      colorectal adenomas.
AB  - The obese patients with diabetes or cardiovascular risk factors are associated
      with increased risk of colorectal cancer as well as adenomas under the shared
      pathogenesis related to atherosclerosis. Here we determined the association
      between increased arterial stiffness and colorectal adenomas incorporating
      parameters including age, gender, waist circumference, body mass index, lipid
      profiles, fasting glucose, and blood pressure. Subjects who simultaneously
      underwent colonoscopies and pulse wave velocity (PWV) determinations between July
      2005 and September 2006 were analyzed, based on which the subjects were
      classified into two groups as patients group with colorectal adenomas (n = 49)
      and control group (n = 200) with normal, non-polypoid benign lesions or
      hyperplastic polyps. Uni- and multi-variate analyses were performed to calculate
      the odd ratio for colon adenomas. Based on uni-variate analysis, age, waist
      circumference, body mass index, heart-femoral PWV (hfPWV), and brachial-ankle PWV
      were significantly associated with adenomas (p<0.05) and multiple logistic
      regression analysis showed that the heart-femoral PWV, waist circumference, and
      the levels of LDL-C were significant risk factor for colorectal adenoma. However,
      arterial stiffness did not affect the progression of colon adenoma. The finding
      that hfPWV, reflecting aortic stiffness, was increased in patients with
      colorectal adenomas lead to conclusion that patients who have prominently
      increased arterial stiffness can be recommended to undergo colonoscopic
      examinations and at the same time we also recommend counseling about the risk for
      atherosclerosis in those who have colorectal adenomas.

PMID- 21103037
TI  - Erratum.
AB  - [This corrects the article on p. 224-228 in vol. 46.].

PMID- 21103038
TI  - Editorial letter.

PMID- 21103039
TI  - Automatic 3D Shape Severity Quantification and Localization for Deformational
      Plagiocephaly.
AB  - Recent studies have shown an increase in the occurrence of deformational
      plagiocephaly and brachycephaly in children. This increase has coincided with the
      "Back to Sleep" campaign that was introduced to reduce the risk of Sudden Infant
      Death Syndrome (SIDS). However, there has yet to be an objective quantification
      of the degree of severity for these two conditions. Most diagnoses are done on
      subjective factors such as patient history and physician examination. The
      existence of an objective quantification would help research in areas of
      diagnosis and intervention measures, as well as provide a tool for finding
      correlation between the shape severity and cognitive outcome. This paper
      describes a new shape severity quantification and localization method for
      deformational plagiocephaly and brachycephaly. Our results show that there is a
      positive correlation between the new shape severity measure and the scores
      entered by a human expert.

PMID- 21103041
TI  - Potentials of mean force for protein structure prediction vindicated, formalized
      and generalized.
AB  - Understanding protein structure is of crucial importance in science, medicine and
      biotechnology. For about two decades, knowledge-based potentials based on
      pairwise distances--so-called "potentials of mean force" (PMFs)--have been center
      stage in the prediction and design of protein structure and the simulation of
      protein folding. However, the validity, scope and limitations of these potentials
      are still vigorously debated and disputed, and the optimal choice of the
      reference state--a necessary component of these potentials--is an unsolved
      problem. PMFs are loosely justified by analogy to the reversible work theorem in
      statistical physics, or by a statistical argument based on a likelihood function.
      Both justifications are insightful but leave many questions unanswered. Here, we
      show for the first time that PMFs can be seen as approximations to quantities
      that do have a rigorous probabilistic justification: they naturally arise when
      probability distributions over different features of proteins need to be
      combined. We call these quantities "reference ratio distributions" deriving from
      the application of the "reference ratio method." This new view is not only of
      theoretical relevance but leads to many insights that are of direct practical
      use: the reference state is uniquely defined and does not require external
      physical insights; the approach can be generalized beyond pairwise distances to
      arbitrary features of protein structure; and it becomes clear for which purposes
      the use of these quantities is justified. We illustrate these insights with two
      applications, involving the radius of gyration and hydrogen bonding. In the
      latter case, we also show how the reference ratio method can be iteratively
      applied to sculpt an energy funnel. Our results considerably increase the
      understanding and scope of energy functions derived from known biomolecular
      structures.

PMID- 21103042
TI  - Gene expression in the scleractinian Acropora microphthalma exposed to high solar
      irradiance reveals elements of photoprotection and coral bleaching.
AB  - BACKGROUND: The success of tropical reef-building corals depends on the metabolic
      co-operation between the animal host and the photosynthetic performance of
      endosymbiotic algae residing within its cells. To examine the molecular response
      of the coral Acropora microphthalma to high levels of solar irradiance, a cDNA
      library was constructed by PCR-based suppression subtractive hybridisation (PCR
      SSH) from mRNA obtained by transplantation of a colony from a depth of 12.7 m to
      near-surface solar irradiance, during which the coral became noticeably paler
      from loss of endosymbionts in sun-exposed tissues. METHODOLOGY/PRINCIPAL
      FINDINGS: A novel approach to sequence annotation of the cDNA library gave
      genetic evidence for a hypothetical biosynthetic pathway branching from the
      shikimic acid pathway that leads to the formation of 4-deoxygadusol. This
      metabolite is a potent antioxidant and expected precursor of the UV-protective
      mycosporine-like amino acids (MAAs), which serve as sunscreens in coral
      phototrophic symbiosis. Empirical PCR based evidence further upholds the
      contention that the biosynthesis of these MAA sunscreens is a 'shared metabolic
      adaptation' between the symbiotic partners. Additionally, gene expression induced
      by enhanced solar irradiance reveals a cellular mechanism of light-induced coral
      bleaching that invokes a Ca(2+)-binding synaptotagmin-like regulator of SNARE
      protein assembly of phagosomal exocytosis, whereby algal partners are lost from
      the symbiosis. CONCLUSIONS/SIGNIFICANCE: Bioinformatics analyses of DNA sequences
      obtained by differential gene expression of a coral exposed to high solar
      irradiance has revealed the identification of putative genes encoding key steps
      of the MAA biosynthetic pathway. Revealed also by this treatment are genes that
      implicate exocytosis as a cellular process contributing to a breakdown in the
      metabolically essential partnership between the coral host and endosymbiotic
      algae, which manifests as coral bleaching.

PMID- 21103043
TI  - Activation of functional alpha7-containing nAChRs in hippocampal CA1 pyramidal
      neurons by physiological levels of choline in the presence of PNU-120596.
AB  - BACKGROUND: The level of expression of functional alpha7-containing nicotinic
      acetylcholine receptors (nAChRs) in hippocampal CA1 pyramidal neurons is believed
      to be very low compared to hippocampal CA1 interneurons, and for many years this
      expression was largely overlooked. However, high densities of expression of
      functional alpha7-containing nAChRs in CA1 pyramidal neurons may not be necessary
      for triggering important cellular and network functions, especially if activation
      of alpha7-containing nAChRs occurs in the presence of positive allosteric
      modulators such as PNU-120596. METHODOLOGY/PRINCIPAL FINDINGS: An approach
      previously developed for alpha7-containing nAChRs expressed in tuberomammillary
      neurons was applied to investigate functional CA1 pyramidal alpha7-containing
      nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology.
      The majority (~71%) of tested CA1 pyramidal neurons expressed low densities of
      functional alpha7-containing nAChRs as evidenced by small whole-cell responses to
      choline, a selective endogenous agonist of alpha7 nAChRs. These responses were
      potentiated by PNU-120596, a novel positive allosteric modulator of alpha7
      nAChRs. The density of functional alpha7-containing nAChRs expressed in CA1
      pyramidal neurons (and thus, the normalized net effect of activation, i.e.,
      response net charge per unit of membrane capacitance per unit of time) was
      estimated to be ~5% of the density observed in CA1 interneurons. The results of
      this study demonstrate that despite low levels of expression of functional
      pyramidal alpha7-containing nAChRs, physiological levels of choline (~10 uM) are
      sufficient to activate these receptors and transiently depolarize and even excite
      CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are
      possible because in the presence of 10 uM choline and 1-5 uM PNU-120596, a single
      opening of an individual pyramidal alpha7-containing nAChR ion channel appears to
      transiently depolarize (~4 mV) the entire pyramidal neuron and occasionally
      trigger action potentials. CONCLUSIONS: 1) The majority of hippocampal CA1
      pyramidal neurons express functional alpha7-containing nAChRs. In the absence of
      PNU-120596, a positive allosteric modulator of alpha7 nAChRs, a lack of
      responsiveness of some hippocampal CA1 pyramidal neurons to focal application of
      0.5-1 mM choline does not imply a lack of expression of functional alpha7
      containing nAChRs in these neurons. Rather, it may indicate a lack of detection
      of alpha7-containing nAChR-mediated currents by patch-clamp electrophysiology. 2)
      PNU-120596 can serve as a powerful tool for detection and enhancement of
      responsiveness of low densities of functional alpha7-containing nAChRs such as
      those present in hippocampal CA1 pyramidal neurons. 3) In the presence of PNU
      120596, physiological concentrations of choline activate functional CA1 pyramidal
      alpha7-containing nAChRs and produce step-like currents that cause repetitive
      step-like depolarizations, occasionally triggering bursts of action potentials in
      CA1 pyramidal neurons. Therefore, the results of this study suggest that in the
      presence of PNU-120596 and possibly other positive allosteric modulators,
      endogenous choline may persistently activate CA1 pyramidal alpha7-containing
      nAChRs, enhance the excitability of CA1 pyramidal neurons and thus act as a
      potent therapeutic agent with potential neuroprotective and cognition-enhancing
      properties.

PMID- 21103044
TI  - Rapid transient production in plants by replicating and non-replicating vectors
      yields high quality functional anti-HIV antibody.
AB  - BACKGROUND: The capacity of plants and plant cells to produce large amounts of
      recombinant protein has been well established. Due to advantages in terms of
      speed and yield, attention has recently turned towards the use of transient
      expression systems, including viral vectors, to produce proteins of
      pharmaceutical interest in plants. However, the effects of such high level
      expression from viral vectors and concomitant effects on host cells may affect
      the quality of the recombinant product. METHODOLOGY/PRINCIPAL FINDINGS: To assess
      the quality of antibodies transiently expressed to high levels in plants, we have
      expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using
      both replicating and non-replicating systems based on deleted versions of Cowpea
      mosaic virus (CPMV) RNA-2. The highest yield (approximately 100 mg/kg wet weight
      leaf tissue) of affinity purified 2G12 was obtained when the non-replicating CPMV
      HT system was used and the antibody was retained in the endoplasmic reticulum
      (ER). Glycan analysis by mass-spectrometry showed that the glycosylation pattern
      was determined exclusively by whether the antibody was retained in the ER and did
      not depend on whether a replicating or non-replicating system was used.
      Characterisation of the binding and neutralisation properties of all the purified
      2G12 variants from plants showed that these were generally similar to those of
      the Chinese hamster ovary (CHO) cell-produced 2G12. CONCLUSIONS: Overall, the
      results demonstrate that replicating and non-replicating CPMV-based vectors are
      able to direct the production of a recombinant IgG similar in activity to the CHO
      produced control. Thus, a complex recombinant protein was produced with no
      apparent effect on its biochemical properties using either high-level expression
      or viral replication. The speed with which a recombinant pharmaceutical with
      excellent biochemical characteristics can be produced transiently in plants makes
      CPMV-based expression vectors an attractive option for biopharmaceutical
      development and production.

PMID- 21103045
TI  - Cross-platform microarray data normalisation for regulatory network inference.
AB  - BACKGROUND: Inferring Gene Regulatory Networks (GRNs) from time course microarray
      data suffers from the dimensionality problem created by the short length of
      available time series compared to the large number of genes in the network. To
      overcome this, data integration from diverse sources is mandatory. Microarray
      data from different sources and platforms are publicly available, but integration
      is not straightforward, due to platform and experimental differences. METHODS: We
      analyse here different normalisation approaches for microarray data integration,
      in the context of reverse engineering of GRN quantitative models. We introduce
      two preprocessing approaches based on existing normalisation techniques and
      provide a comprehensive comparison of normalised datasets. CONCLUSIONS: Results
      identify a method based on a combination of Loess normalisation and iterative K
      means as best for time series normalisation for this problem.

PMID- 21103046
TI  - Adverse drug reactions related hospital admissions in persons aged 60 years and
      over, The Netherlands, 1981-2007: less rapid increase, different drugs.
AB  - BACKGROUND: Epidemiologic information on time trends of Adverse Drug Reactions
      (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has
      become increasingly complex. Because of raised awareness of ADR, a decrease in
      ADR might be expected. The aim of this study was to determine trends in ADR
      related hospitalizations in the older Dutch population. METHODOLOGY AND PRINCIPAL
      FINDINGS: Secular trend analysis of ADR-related hospital admissions in patients
      >=60 years between 1981 and 2007, using the National Hospital Discharge Registry
      of The Netherlands. Numbers, age-specific and age-adjusted incidence rates (per
      10,000 persons) of ADR-related hospital admissions were used as outcome measures
      in each year of the study. Between 1981 and 2007, ADR-related hospital admissions
      in persons >=60 years increased by 143%. The overall standardized incidence rate
      increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in
      males than in females. Since 1997, the increase in incidence rates of ADR-related
      hospitalizations flattened (percentage annual change 0.65%), compared to the
      period 1981-1996 (percentage annual change 2.56%). CONCLUSION/SIGNIFICANCE: ADR
      related hospital admissions in older persons have shown a rapidly increasing
      trend in The Netherlands over the last three decades with a temporization since
      1997. Although an encouraging flattening in the increasing trend of ADR-related
      admissions was found around 1997, the incidence is still rising, which warrants
      sustained attention to this problem.

PMID- 21103047
TI  - The Terneuzen Birth Cohort: BMI change between 2 and 6 years is most predictive
      of adult cardiometabolic risk.
AB  - BACKGROUND: We recently reported the age interval 2-6y being the earliest and
      most critical for adult overweight. We now aim to determine which age intervals
      are predictive of cardiometabolic risk at young adulthood. METHODS AND FINDINGS:
      We analyzed data from 642 18-28 years olds from the Terneuzen Birth Cohort.
      Individual BMI SDS trajectories were fitted by a piecewise linear model. By
      multiple regression analyses relationships were assessed between subsequent
      conditional BMI SDS changes and components of the metabolic syndrome (MetS),
      skinfold thickness and hsCRP at young adulthood. Results were adjusted for gender
      and age, and other confounders. Gender was studied as an effect modifier. All BMI
      SDS changes throughout childhood were related to waist circumference and skinfold
      thickness. No other significant relationship was found before the age of 2 years,
      except between the BMI SDS change 0-1y and hsCRP. Fasting blood glucose was not
      predicted by any BMI SDS change. BMI SDS change 2-6y was strongly related to most
      outcome variables, especially to waist circumference (beta 0.47, SE 0.02),
      systolic and diastolic blood pressure (beta 0.20 SE 0.04 and beta 0.19 SE 0.03),
      and hsCRP (beta 0.16 SE 0.04). The BMI SDS change 10-18y was most strongly
      related to HDL cholesterol (beta -0.10, SE 0.03), and triglycerides (beta 0.21,
      SE 0.03). To a lesser degree, the BMI SDS change 6-10y was related to most
      outcome variables. BMI SDS changes 2-6y and 10-18y were significantly related to
      MetS: the OR was respectively 3.39 (95%CI 2.33-4.94) and 2.84 (95%CI 1.94-4.15).
      CONCLUSION: BMI SDS changes from 2y onwards were related to cardiometabolic risk
      at young adulthood, the age interval 2-6y being the most predictive. Monitoring
      and stabilizing the BMI SDS of children as young as 2-6y may not only reverse the
      progression towards adult overweight, but it may also safeguard cardiometabolic
      status.

PMID- 21103048
TI  - BurkDiff: a real-time PCR allelic discrimination assay for Burkholderia
      pseudomallei and B. mallei.
AB  - A real-time PCR assay, BurkDiff, was designed to target a unique conserved region
      in the B. pseudomallei and B. mallei genomes containing a SNP that differentiates
      the two species. Sensitivity and specificity were assessed by screening BurkDiff
      across 469 isolates of B. pseudomallei, 49 isolates of B. mallei, and 390
      isolates of clinically relevant non-target species. Concordance of results with
      traditional speciation methods and no cross-reactivity to non-target species show
      BurkDiff is a robust, highly validated assay for the detection and
      differentiation of B. pseudomallei and B. mallei.

PMID- 21103049
TI  - DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA
      PTEN-TP53 related to age at disease onset.
AB  - The incidence of colorectal cancer (CRC) increases with age and early onset
      indicates an increased likelihood for genetic predisposition for this disease.
      The somatic genetics of tumor development in relation to patient age remains
      mostly unknown. We have examined the mutation status of five known cancer
      critical genes in relation to age at diagnosis, and compared the genomic
      complexity of tumors from young patients without known CRC syndromes with those
      from elderly patients. Among 181 CRC patients, stratified by microsatellite
      instability status, DNA sequence changes were identified in KRAS (32%), BRAF
      (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years
      (n = 45), PIK3CA mutations were not observed and TP53 mutations were more
      frequent than in the older age groups. The total gene mutation index was lowest
      in tumors from the youngest patients. In contrast, the genome complexity,
      assessed as copy number aberrations, was highest in tumors from the youngest
      patients. A comparable number of tumors from young (<50 years) and old patients
      (>70 years) was quadruple negative for the four predictive gene markers (KRAS
      BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had
      tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing
      for prediction of EGFR treatment response may be restricted to KRAS and BRAF in
      elderly (>70 years) patients. Distinct genetic differences found in tumors from
      young and elderly patients, whom are comparable for known clinical and
      pathological variables, indicate that young patients have a different genetic
      risk profile for CRC development than older patients.

PMID- 21103050
TI  - Analysing the large decline in coronary heart disease mortality in the Icelandic
      population aged 25-74 between the years 1981 and 2006.
AB  - BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in
      Iceland since the 1980s. We examined how much of the decrease between 1981 and
      2006 could be attributed to medical and surgical treatments and how much to
      changes in cardiovascular risk factors. METHODOLOGY: The previously validated
      IMPACT CHD mortality model was applied to the Icelandic population. The data
      sources were official statistics, national quality registers, published trials
      and meta-analyses, clinical audits and a series of national population surveys.
      PRINCIPAL FINDINGS: Between 1981 and 2006, CHD mortality rates in Iceland
      decreased by 80% in men and women aged 25 to 74 years, which resulted in 295
      fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of
      myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer
      incident MI cases per year, which is a major determinant of possible deaths from
      MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates:
      54%-93%) of the mortality decrease was attributable to risk factor reductions:
      cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical
      inactivity 5% with adverse trends for diabetes (-5%), and obesity (-4%).
      Approximately 25% (lower and upper bound estimates: 8%-40%) of the mortality
      decrease was attributable to treatments in individuals: secondary prevention 8%;
      heart failure treatments 6%; acute coronary syndrome treatments 5%;
      revascularisation 3%; hypertension treatments 2%, and statins 0.5%. CONCLUSIONS:
      Almost three quarters of the large CHD mortality decrease in Iceland between 1981
      and 2006 was attributable to reductions in major cardiovascular risk factors in
      the population. These findings emphasize the value of a comprehensive prevention
      strategy that promotes tobacco control and a healthier diet to reduce incidence
      of MI and highlights the potential importance of effective, evidence based
      medical treatments.

PMID- 21103051
TI  - An empirical strategy for characterizing bacterial proteomes across species in
      the absence of genomic sequences.
AB  - Global protein identification through current proteomics methods typically
      depends on the availability of sequenced genomes. In spite of increasingly high
      throughput sequencing technologies, this information is not available for every
      microorganism and rarely available for entire microbial communities.
      Nevertheless, the protein-level homology that exists between related bacteria
      makes it possible to extract biological information from the proteome of an
      organism or microbial community by using the genomic sequences of a near neighbor
      organism. Here, we demonstrate a trans-organism search strategy for determining
      the extent to which near-neighbor genome sequences can be applied to identify
      proteins in unsequenced environmental isolates. In proof of concept testing, we
      found that within a CLUSTAL W distance of 0.089, near-neighbor genomes
      successfully identified a high percentage of proteins within an organism.
      Application of this strategy to characterize environmental bacterial isolates
      lacking sequenced genomes, but having 16S rDNA sequence similarity to Shewanella
      resulted in the identification of 300-500 proteins in each strain. The majority
      of identified pathways mapped to core processes, as well as to processes unique
      to the Shewanellae, in particular to the presence of c-type cytochromes. Examples
      of core functional categories include energy metabolism, protein and nucleotide
      synthesis and cofactor biosynthesis, allowing classification of bacteria by
      observation of conserved processes. Additionally, within these core
      functionalities, we observed proteins involved in the alternative lactate
      utilization pathway, recently described in Shewanella.

PMID- 21103052
TI  - Multi-class clustering of cancer subtypes through SVM based ensemble of pareto
      optimal solutions for gene marker identification.
AB  - With the advancement of microarray technology, it is now possible to study the
      expression profiles of thousands of genes across different experimental
      conditions or tissue samples simultaneously. Microarray cancer datasets,
      organized as samples versus genes fashion, are being used for classification of
      tissue samples into benign and malignant or their subtypes. They are also useful
      for identifying potential gene markers for each cancer subtype, which helps in
      successful diagnosis of particular cancer types. In this article, we have
      presented an unsupervised cancer classification technique based on multiobjective
      genetic clustering of the tissue samples. In this regard, a real-coded encoding
      of the cluster centers is used and cluster compactness and separation are
      simultaneously optimized. The resultant set of near-Pareto-optimal solutions
      contains a number of non-dominated solutions. A novel approach to combine the
      clustering information possessed by the non-dominated solutions through Support
      Vector Machine (SVM) classifier has been proposed. Final clustering is obtained
      by consensus among the clusterings yielded by different kernel functions. The
      performance of the proposed multiobjective clustering method has been compared
      with that of several other microarray clustering algorithms for three publicly
      available benchmark cancer datasets. Moreover, statistical significance tests
      have been conducted to establish the statistical superiority of the proposed
      clustering method. Furthermore, relevant gene markers have been identified using
      the clustering result produced by the proposed clustering method and demonstrated
      visually. Biological relationships among the gene markers are also studied based
      on gene ontology. The results obtained are found to be promising and can possibly
      have important impact in the area of unsupervised cancer classification as well
      as gene marker identification for multiple cancer subtypes.

PMID- 21103053
TI  - Economic conditions predict prevalence of West Nile virus.
AB  - Understanding the conditions underlying the proliferation of infectious diseases
      is crucial for mitigating future outbreaks. Since its arrival in North America in
      1999, West Nile virus (WNV) has led to population-wide declines of bird species,
      morbidity and mortality of humans, and expenditures of millions of dollars on
      treatment and control. To understand the environmental conditions that best
      explain and predict WNV prevalence, we employed recently developed spatial
      modeling techniques in a recognized WNV hotspot, Orange County, California. Our
      models explained 85-95% of the variation of WNV prevalence in mosquito vectors,
      and WNV presence in secondary human hosts. Prevalence in both vectors and humans
      was best explained by economic variables, specifically per capita income, and by
      anthropogenic characteristics of the environment, particularly human population
      and neglected swimming pool density. While previous studies have shown
      associations between anthropogenic change and pathogen presence, results show
      that poorer economic conditions may act as a direct surrogate for environmental
      characteristics related to WNV prevalence. Low-income areas may be associated
      with higher prevalence for a number of reasons, including variations in property
      upkeep, microhabitat conditions conducive to viral amplification in both vectors
      and hosts, host community composition, and human behavioral responses related to
      differences in education or political participation. Results emphasize the
      importance and utility of including economic variables in mapping spatial risk
      assessments of disease.

PMID- 21103054
TI  - Identification of Saccharomyces cerevisiae spindle pole body remodeling factors.
AB  - The Saccharomyces cerevisiae centrosome or spindle pole body (SPB) is a dynamic
      structure that is remodeled in a cell cycle dependent manner. The SPB increases
      in size late in the cell cycle and during most cell cycle arrests and exchanges
      components during G1/S. We identified proteins involved in the remodeling process
      using a strain in which SPB remodeling is conditionally induced. This strain was
      engineered to express a modified SPB component, Spc110, which can be cleaved upon
      the induction of a protease. Using a synthetic genetic array analysis, we
      screened for genes required only when Spc110 cleavage is induced. Candidate SPB
      remodeling factors fell into several functional categories: mitotic regulators,
      microtubule motors, protein modification enzymes, and nuclear pore proteins. The
      involvement of candidate genes in SPB assembly was assessed in three ways: by
      identifying the presence of a synthetic growth defect when combined with an
      Spc110 assembly defective mutant, quantifying growth of SPBs during metaphase
      arrest, and comparing distribution of SPB size during asynchronous growth. These
      secondary screens identified four genes required for SPB remodeling: NUP60,
      POM152, and NCS2 are required for SPB growth during a mitotic cell cycle arrest,
      and UBC4 is required to maintain SPB size during the cell cycle. These findings
      implicate the nuclear pore, urmylation, and ubiquitination in SPB remodeling and
      represent novel functions for these genes.

PMID- 21103055
TI  - RhoH regulates subcellular localization of ZAP-70 and Lck in T cell receptor
      signaling.
AB  - RhoH is an hematopoietic-specific, GTPase-deficient Rho GTPase that plays a role
      in T development. We investigated the mechanisms of RhoH function in TCR
      signaling. We found that the association between Lck and CD3zeta was impaired in
      RhoH-deficient T cells, due to defective translocation of both Lck and ZAP-70 to
      the immunological synapse. RhoH with Lck and ZAP-70 localizes in the detergent
      soluble membrane fraction where the complex is associated with CD3zeta
      phosphorylation. To determine if impaired translocation of ZAP-70 was a major
      determinant of defective T cell development, Rhoh(-/-) bone marrow cells were
      transduced with a chimeric myristoylation-tagged ZAP-70. Myr-ZAP-70 transduced
      cells partially reversed the in vivo defects of RhoH-associated thymic
      development and TCR signaling. Together, our results suggest that RhoH regulates
      TCR signaling via recruitment of ZAP-70 and Lck to CD3zeta in the immunological
      synapse. Thus, we define a new function for a RhoH GTPase as an adaptor molecule
      in TCR signaling pathway.

PMID- 21103056
TI  - Long-lasting priming of endothelial cells by plasma melatonin levels.
AB  - BACKGROUND: Endothelial cells are of great interest for cell therapy and tissue
      engineering. Understanding the heterogeneity among cell lines originating from
      different sources and culture protocols may allow more standardized material to
      be obtained. In a recent paper, we showed that adrenalectomy interferes with the
      expression of membrane adhesion molecules on endothelial cells maintained in
      culture for 16 to 18 days. In addition, the pineal hormone, melatonin, reduces
      the adhesion of neutrophils to post-capillary veins in rats. Here, we evaluated
      whether the reactivity of cultured endothelial cells maintained for more than two
      weeks in culture is inversely correlated to plasma melatonin concentration.
      METHODOLOGY/PRINCIPAL FINDINGS: The nocturnal levels of melatonin were
      manipulated by treating rats with LPS. Nocturnal plasma melatonin, significantly
      reduced two hours after LPS treatment, returned to control levels after six
      hours. Endothelial cells obtained from animals that had lower nocturnal melatonin
      levels significantly express enhanced adhesion molecules and iNOS, and have more
      leukocytes adhered than cells from animals that had normal nocturnal levels of
      melatonin (naive or injected with vehicle). Endothelial cells from animals
      sacrificed two hours after a simultaneous injection of LPS and melatonin present
      similar phenotype and function than those obtained from control animals.
      Analyzing together all the data, taking into account the plasma melatonin
      concentration versus the expression of adhesion molecules or iNOS we detected a
      significant inverse correlation. CONCLUSIONS/SIGNIFICANCE: Our data strongly
      suggest that the plasma melatonin level primes endothelial cells "in vivo,"
      indicating that the state of the donor animal is translated to cells in culture
      and therefore, should be considered for establishing cell banks in ideal
      conditions.

PMID- 21103058
TI  - Social experiments in the mesoscale: humans playing a spatial prisoner's dilemma.
AB  - BACKGROUND: The evolutionary origin of cooperation among unrelated individuals
      remains a key unsolved issue across several disciplines. Prominent among the
      several mechanisms proposed to explain how cooperation can emerge is the
      existence of a population structure that determines the interactions among
      individuals. Many models have explored analytically and by simulation the effects
      of such a structure, particularly in the framework of the Prisoner's Dilemma, but
      the results of these models largely depend on details such as the type of spatial
      structure or the evolutionary dynamics. Therefore, experimental work suitably
      designed to address this question is needed to probe these issues. METHODS AND
      FINDINGS: We have designed an experiment to test the emergence of cooperation
      when humans play Prisoner's Dilemma on a network whose size is comparable to that
      of simulations. We find that the cooperation level declines to an asymptotic
      state with low but nonzero cooperation. Regarding players' behavior, we observe
      that the population is heterogeneous, consisting of a high percentage of
      defectors, a smaller one of cooperators, and a large group that shares features
      of the conditional cooperators of public goods games. We propose an agent-based
      model based on the coexistence of these different strategies that is in good
      agreement with all the experimental observations. CONCLUSIONS: In our large
      experimental setup, cooperation was not promoted by the existence of a lattice
      beyond a residual level (around 20%) typical of public goods experiments. Our
      findings also indicate that both heterogeneity and a "moody" conditional
      cooperation strategy, in which the probability of cooperating also depends on the
      player's previous action, are required to understand the outcome of the
      experiment. These results could impact the way game theory on graphs is used to
      model human interactions in structured groups.

PMID- 21103057
TI  - Gender differences in clinical presentation and outcomes of epidemic Kaposi
      sarcoma in Uganda.
AB  - INTRODUCTION: The incidence of Kaposi sarcoma (KS) has increased dramatically
      among women in sub-Saharan Africa since the onset of the HIV pandemic, but data
      on KS disease in women are limited. To identify gender-related differences in KS
      presentation and outcomes, we evaluated the clinical manifestations and response
      in men and women with AIDS-associated KS in Uganda. METHODS AND FINDINGS: HIV
      infected adults with KS attending the Infectious Diseases Institute (IDI) and
      Uganda Cancer Institute (UCI) in Kampala, Uganda between 2004 and 2006 were
      included in a retrospective cohort. Evaluation of KS presentation was based on
      the clinical features described at the initial KS visit. Response was evaluated
      as the time to "improvement", as defined by any decrease in lesion size, lesion
      number, or edema. The cohort consisted of 197 adults with HIV and KS: 55%
      (108/197) were women. At presentation, the median CD4 T-cell count was
      significantly lower in women (58 cells/mm(3); IQR 11-156 cells/mm(3)) than men
      (124 cells/mm(3); IQR 22-254 cells/mm(3)) (p = 0.02). Women were more likely than
      men to present with lesions of the face (OR 2.8, 95% CI, 1.4, 5.7; p = 0.005) and
      hard palate (OR 2.0, 95% CI, 1.1, 3.7; p = 0.02), and were less likely than men
      to have lower extremity lesions (OR 0.54, 95% CI, 0.3, 0.99; p = 0.05). Women
      were less likely than men to demonstrate clinical improvement (HR = 0.52, CI
      0.31, 0.88; p = 0.01) in multivariate analysis. CONCLUSIONS: The clinical
      presentation and response of KS differs between men and women in Uganda. These
      data suggest that gender affects the pathophysiology of KS, which may have
      implications for the prevention, diagnosis, and treatment of KS in both men and
      women. Prospective studies are needed to identify predictors of response and
      evaluate efficacy of treatment in women with KS, particularly in Africa where the
      disease burden is greatest.

PMID- 21103059
TI  - Suppression of TGFbeta-induced epithelial-mesenchymal transition like phenotype
      by a PIAS1 regulated sumoylation pathway in NMuMG epithelial cells.
AB  - Epithelial-mesenchymal-transition (EMT) is a fundamental cellular process that is
      critical for normal development and tumor metastasis. The transforming growth
      factor beta (TGFbeta) is a potent inducer of EMT like effects, but the mechanisms
      that regulate TGFbeta-induced EMT remain incompletely understood. Using the
      widely employed NMuMG mammary epithelial cells as a model to study TGFbeta
      induced EMT, we report that TGFbeta downregulates the levels of the SUMO E3
      ligase PIAS1 in cells undergoing EMT. Gain and loss of function analyses indicate
      that PIAS1 acts in a SUMO ligase dependent manner to suppress the ability of
      TGFbeta to induce EMT in these cells. We also find that TGFbeta inhibits
      sumoylation of the PIAS1 substrate SnoN, a transcriptional regulator that
      antagonizes TGFbeta-induced EMT. Accordingly, loss of function mutations of SnoN
      sumoylation impair the ability of SnoN to inhibit TGFbeta-induced EMT in NMuMG
      cells. Collectively, our findings suggest that PIAS1 is a novel negative
      regulator of EMT and reveal that inhibition of the PIAS1-SnoN sumoylation pathway
      represents a key mechanism by which TGFbeta induces EMT, with important
      implications in normal development and tumor metastasis.

PMID- 21103060
TI  - Characterization of engineered actin binding proteins that control filament
      assembly and structure.
AB  - BACKGROUND: Eukaryotic cells strictly regulate the structure and assembly of
      their actin filament networks in response to various stimuli. The actin binding
      proteins that control filament assembly are therefore attractive targets for
      those who wish to reorganize actin filaments and reengineer the cytoskeleton.
      Unfortunately, the naturally occurring actin binding proteins include only a
      limited set of pointed-end cappers, or proteins that will block polymerization
      from the slow-growing end of actin filaments. Of the few that are known, most are
      part of large multimeric complexes that are challenging to manipulate.
      METHODOLOGY/PRINCIPAL FINDINGS: We describe here the use of phage display
      mutagenesis to generate of a new class of binding protein that can be targeted to
      the pointed-end of actin. These proteins, called synthetic antigen binders
      (sABs), are based on an antibody-like scaffold where sequence diversity is
      introduced into the binding loops using a novel "reduced genetic code" phage
      display library. We describe effective strategies to select and screen for sABs
      that ensure the generated sABs bind to the pointed-end surface of actin
      exclusively. CONCLUSIONS/SIGNIFICANCE: From our set of pointed-end binders, we
      identify three sABs with particularly useful properties to systematically probe
      actin dynamics: one protein that caps the pointed end, a second that crosslinks
      actin filaments, and a third that severs actin filaments and promotes
      disassembly.

PMID- 21103061
TI  - Osteopontin is required for the early onset of high fat diet-induced insulin
      resistance in mice.
AB  - BACKGROUND: Insulin resistance is manifested in muscle, adipose tissue, and liver
      and is associated with adipose tissue inflammation. The cellular components and
      mechanisms that regulate the onset of diet-induced insulin resistance are not
      clearly defined. METHODOLOGY AND PRINCIPAL FINDINGS: We initially observed
      osteopontin (OPN) mRNA over-expression in adipose tissue of obese, insulin
      resistant humans and rats which was normalized by thiazolidinedione (TZD)
      treatment in both species. OPN regulates inflammation and is implicated in
      pathogenic maladies resulting from chronic obesity. Thus, we tested the
      hypothesis that OPN is involved in the early development of insulin resistance
      using a 2-4 week high fat diet (HFD) model. OPN KO mice fed HFD for 2 weeks were
      completely protected from the severe skeletal muscle, liver and adipose tissue
      insulin resistance that developed in wild type (WT) controls, as determined by
      hyperinsulinemic euglycemic clamp and acute insulin-stimulation studies. Although
      two-week HFD did not alter body weight or plasma free fatty acids and cytokines
      in either strain, HFD-induced hyperleptinemia, increased adipose tissue
      inflammation (macrophages and cytokines), and adipocyte hypertrophy were
      significant in WT mice and blunted or absent in OPN KO mice. Adipose tissue OPN
      protein isoform expression was significantly altered in 2- and 4-week HFD-fed WT
      mice but total OPN protein was unchanged. OPN KO bone marrow stromal cells were
      more osteogenic and less adipogenic than WT cells in vitro. Interestingly, the
      two differentiation pathways were inversely affected by HFD in WT cells in vitro.
      CONCLUSIONS: The OPN KO phenotypes we report reflect protection from insulin
      resistance that is associated with changes in adipocyte biology and adipose
      tissue inflammatory status. OPN is a key component in the development of HFD
      induced insulin resistance.

PMID- 21103063
TI  - A versatile molecular tagging method for targeting proteins to avian reovirus
      muNS inclusions. Use in protein immobilization and purification.
AB  - BACKGROUND: Avian reoviruses replicate in viral factories, which are dense
      cytoplasmic compartments established by protein-protein interactions. The non
      structural protein muNS forms the factory scaffold that attracts other viral
      components in a controlled fashion. To create such a three-dimensional network,
      muNS uses several different self-interacting domains. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study we have devised a strategy to identify muNS regions
      containing self-interacting domains, based on the capacity of muNS-derived
      inclusions to recruit muNS fragments. The results revealed that the muNS region
      consisting of residues 477-542 was recruited with the best efficiency, and this
      raised the idea of using this fragment as a molecular tag for delivering foreign
      proteins to muNS inclusions. By combining such tagging system with our previously
      established method for purifying muNS inclusions from baculovirus-infected insect
      cells, we have developed a novel protein purification protocol.
      CONCLUSIONS/SIGNIFICANCE: We show that our tagging and inclusion-targeting system
      can be a simple, versatile and efficient method for immobilizing and purifying
      active proteins expressed in baculovirus-infected cells. We also demonstrate that
      muNS inclusions can simultaneously recruit several tagged proteins, a finding
      which may be used to generate protein complexes and create multiepitope
      particulate material for immunization purposes.

PMID- 21103064
TI  - Modeling the spread of vector-borne diseases on bipartite networks.
AB  - BACKGROUND: Vector-borne diseases for which transmission occurs exclusively
      between vectors and hosts can be modeled as spreading on a bipartite network.
      METHODOLOGY/PRINCIPAL FINDINGS: In such models the spreading of the disease
      strongly depends on the degree distribution of the two classes of nodes. It is
      sufficient for one of the classes to have a scale-free degree distribution with a
      slow enough decay for the network to have asymptotically vanishing epidemic
      threshold. Data on the distribution of Ixodes ricinus ticks on mice and lizards
      from two independent studies are well described by a scale-free distribution
      compatible with an asymptotically vanishing epidemic threshold. The commonly used
      negative binomial, instead, cannot describe the right tail of the empirical
      distribution. CONCLUSIONS/SIGNIFICANCE: The extreme aggregation of vectors on
      hosts, described by the power-law decay of the degree distribution, makes the
      epidemic threshold decrease with the size of the network and vanish
      asymptotically.

PMID- 21103062
TI  - Unifying candidate gene and GWAS Approaches in Asthma.
AB  - The first genome wide association study (GWAS) for childhood asthma identified a
      novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene,
      but the role of previous asthma candidate genes was not specifically analyzed in
      this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously
      associated with asthma in >3 independent study populations. We re-genotyped 39
      SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658
      reference children. Genotyping data were compared to imputation data derived from
      Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs
      covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and
      VDR showed effects with p-values <0.0035 (corrected for multiple testing).
      Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13,
      IL4, IL4R and TNF showed associations at a significance level between p = 0.05
      and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for
      many asthma candidate genes, (b) imputation based on these data is reliable but
      incomplete, and (c) SNPs in three previously identified asthma candidate genes
      replicate in our GWAS population with significance after correction for multiple
      testing in 14 genes.

PMID- 21103065
TI  - Dentin sialophosphoprotein (DSPP) gene-silencing inhibits key tumorigenic
      activities in human oral cancer cell line, OSC2.
AB  - BACKGROUND: We determined recently that dentin sialophosphoprotein (DSPP), a
      member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins)
      family of phosphoglycoproteins, is highly upregulated in human oral squamous cell
      carcinomas (OSCCs) where upregulation is associated with tumor aggressiveness. To
      investigate the effects of DSPP-silencing on the tumorigenic profiles of the oral
      cancer cell line, OSC2, short-hairpin RNA (shRNA) interference was employed to
      silence DSPP in OSC2 cells. METHODOLOGY/PRINCIPAL FINDINGS: Multiple regions of
      DSPP transcript were targeted for shRNA interference using hDSP-shRNA lentiviral
      particles designed to silence DSPP gene expression. Control shRNA plasmid
      encoding a scrambled sequence incapable of degrading any known cellular mRNA was
      used for negative control. Following puromycin selection of stable lines of DSSP
      silenced OSC2 cells, phenotypic hallmarks of oral carcinogenesis were assayed by
      western blot and RT-PCR analyses, MTT (cell-viability), colony-formation,
      modified Boyden-Chamber (migration and invasion), and flow cytometry (cell-cycle
      and apoptosis) analyses. DSPP-silenced OSC2 cells showed altered cell morphology,
      reduced viability, decreased colony-formation ability, decreased migration and
      invasion, G0/G1 cell-cycle arrest, and increased tumor cell sensitivity to
      cisplatin-induced apoptosis. Furthermore, MMP-2, MMP-3, MMP-9, VEGF, Ki-67, p53,
      and EGFR were down-regulated. There was a direct correlation between the degree
      of DSPP-silencing and MMP suppression, as indicated by least squares regression:
      MMP-2 {(y = 0.850x, p<0.001) (y = 1.156x, p<0.001)}, MMP-3 {(y = 0.994x, p<0.001)
      (y = 1.324x, p = 0.004)}, and MMP-9 {(y = 1.248x, p = 0.005, y = 0.809, p =
      0.013)}. CONCLUSIONS/SIGNIFICANCE: DSPP-silencing in OSC2 cell decreased salient
      hallmarks of oral tumorigenesis and provides the first functional evidence of a
      potential key role for DSPP in oral cancer biology. The down-regulation of MMP-2,
      MMP-3, MMP-9, p53 and VEGF in DSPP-silenced OSC2 cells provides a significant
      functional/molecular framework for deciphering the mechanisms of DSPP activities
      in oral cancer biology.

PMID- 21103066
TI  - Characterization of the fecal microbiome from non-human wild primates reveals
      species specific microbial communities.
AB  - BACKGROUND: Host-associated microbes comprise an integral part of animal
      digestive systems and these interactions have a long evolutionary history. It has
      been hypothesized that the gastrointestinal microbiome of humans and other non
      human primates may have played significant roles in host evolution by
      facilitating a range of dietary adaptations. We have undertaken a comparative
      sequencing survey of the gastrointestinal microbiomes of several non-human
      primate species, with the goal of better understanding how these microbiomes
      relate to the evolution of non-human primate diversity. Here we present a
      comparative analysis of gastrointestinal microbial communities from three
      different species of Old World wild monkeys. METHODOLOGY/PRINCIPAL FINDINGS: We
      analyzed fecal samples from three different wild non-human primate species (black
      and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and
      red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were
      subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast
      majority of the phyla in each sample. Other phyla represented were
      Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia,
      Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis
      similarity analysis of these microbiomes indicated that microbial community
      composition within the same primate species are more similar to each other than
      to those of different primate species. Comparison of fecal microbiota from non
      human primates with microbiota of human stool samples obtained in previous
      studies revealed that the gut microbiota of these primates are distinct and
      reflect host phylogeny. CONCLUSION/SIGNIFICANCE: Our analysis provides evidence
      that the fecal microbiomes of wild primates co-vary with their hosts, and that
      this is manifested in higher intraspecies similarity among wild primate species,
      perhaps reflecting species specificity of the microbiome in addition to dietary
      influences. These results contribute to the limited body of primate microbiome
      studies and provide a framework for comparative microbiome analysis between human
      and non-human primates as well as a comparative evolutionary understanding of the
      human microbiome.